11mmHg at 1 year
(10.4% vs 9.9% vs 10.0%, p=0.980) and 4 years (16.8% vs 21.9% vs 19.2%, p=0.353)
respectively. In multivariate analysis, PCWP was not independently predictive of
4-year all-cause mortality [HR 1.00, 95%CI 0.95-1.05, p=0.98 (permmHg)].
Predictors of 4-year mortality included older age [HR 1.02, 95%CI 1.00-1.03,
p=0.0091 (per year)], non-Caucasian race, and higher PVR [HR 1.06, 95% CI 1.04
1.08, p<0.0001 (per Woods Unit)]. CONCLUSIONS: In this study of patients with PAH
receiving parenteral treprostinil, PCWP was not associated with long-term all
cause mortality. Further studies examining prognostic indicators in patients with
PAH optimised on guideline-based therapies are warranted.
PMID- 28400192
TI - Pulmonary Arteriovenous Malformation Detected by Three-dimensional Computed
Tomographic Angiography.
PMID- 28400193
TI - Autologous Mesenchymal Stem Cells, Applied in a Bioabsorbable Matrix, for
Treatment of Perianal Fistulas in Patients With Crohn's Disease.
AB - In patients with Crohn's disease, perianal fistulas recur frequently, causing
substantial morbidity. We performed a 12-patient, 6-month, phase 1 trial to
determine whether autologous mesenchymal stem cells, applied in a bioabsorbable
matrix, can heal the fistula. Fistula repair was not associated with any serious
adverse events related to mesenchymal stem cells or plug placement. At 6 months,
10 of 12 patients (83%) had complete clinical healing and radiographic markers of
response. We found placement of mesenchymal stem cell-coated matrix fistula plugs
in 12 patients with chronic perianal fistulas to be safe and lead to clinical
healing and radiographic response in 10 patients. ClinicalTrials.gov Identifier:
NCT01915927.
PMID- 28400194
TI - Increased Risk of Colorectal Cancer in Patients With Multiple Serrated Polyps and
Their First-Degree Relatives.
AB - BACKGROUND & AIMS: We investigated whether patients with multiple serrated
polyps, but not meeting the World Health Organization criteria for serrated
polyposis syndrome, and their relatives have similar risks for colorectal cancer
(CRC) as those diagnosed with serrated polyposis. METHODS: We collected data from
patients with more than 10 colonic polyps, recruited in 2008-2009 from 24
hospitals in Spain for a study of causes of multiple colonic polyps. We analyzed
data from 53 patients who met the criteria for serrated polyposis and 145
patients who did not meet these criteria, but who had more than 10 polyps
throughout the colon, of which more than 50% were serrated. We calculated age-
and sex-adjusted standardized incidence ratios (SIRs) for CRC in both groups, as
well as in their first-degree relatives. RESULTS: The prevalence of CRC was
similar between patients with confirmed serrated polyposis and multiple serrated
polyps (odds ratio, 1.35; 95% confidence interval [CI], 0.64-2.82; P = .40). The
SIR for CRC in patients with serrated polyposis (0.51; 95% CI, 0.01-2.82) did not
differ significantly from the SIR for CRC in patients with multiple serrated
polyps (0.74; 95% CI, 0.20-1.90; P = .70). The SIR for CRC also did not differ
significantly between first-degree relatives of these groups (serrated polyposis:
3.28, 95% CI, 2.16-4.77; multiple serrated polyps: 2.79, 95% CI, 2.10-3.63; P =
.50). Kaplan-Meier analysis showed no differences in the incidence of CRC between
groups during the follow-up period (log-rank, 0.6). CONCLUSIONS: The risk of CRC
in patients with multiple serrated polyps who do not meet the criteria for
serrated polyposis, and in their first-degree relatives, is similar to that of
patients diagnosed with serrated polyposis.
PMID- 28400195
TI - EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer
in Mice and Associates With Outcomes of Patients.
AB - BACKGROUND & AIMS: Inhibitors of the epidermal growth factor receptor (EGFR) are
the first-line therapy for patients with metastatic colorectal tumors without RAS
mutations. However, EGFR inhibitors are ineffective in these patients, and tumor
level of EGFR does not associate with response to therapy. We screened human
colorectal tumors for EGFR-positive myeloid cells and investigated their
association with patient outcome. We also performed studies in mice to evaluate
how EGFR expression in tumor cells and myeloid cells contributes to development
of colitis-associated cancer and ApcMin-dependent intestinal tumorigenesis.
METHODS: We performed immunohistochemical and immunofluorescent analyses of 116
colorectal tumor biopsies to determine levels of EGFR in tumor and stroma; we
also collected information on tumor stage and patient features and outcomes. We
used the Mann-Whitney U and Kruskal-Wallis tests to correlate tumor levels of
EGFR with tumor stage, and the Kaplan-Meier method to estimate patients' median
survival time. We performed experiments in mice lacking EGFR in intestinal
epithelial cells (Villin-Cre; Egfrf/f and Villin-CreERT2; Egfrf/f mice) or
myeloid cells (LysM-Cre; Egfrf/f mice) on a mixed background. These mice were
bred with ApcMin/+ mice; colitis-associated cancer and colitis were induced by
administration of dextran sodium sulfate (DSS), with or without azoxymethane
(AOM), respectively. Villin-CreERT2 was activated in developed tumors by
administration of tamoxifen to mice. Littermates that expressed full-length EGFR
were used as controls. Intestinal tissues were collected; severity of colitis,
numbers and size of tumors, and intestinal barrier integrity were assessed by
histologic, immunohistochemical, quantitative reverse transcription polymerase
chain reaction, and flow cytometry analyses. RESULTS: We detected EGFR in myeloid
cells in the stroma of human colorectal tumors; myeloid cell expression of EGFR
associated with tumor metastasis and shorter patient survival time. Mice with
deletion of EGFR from myeloid cells formed significantly fewer and smaller tumors
than the respective EGFR-expressing controls in an ApcMin/+ background as well as
after administration of AOM and DSS. Deletion of EGFR from intestinal epithelial
cells did not affect tumor growth. Furthermore, tamoxifen-induced deletion of
EGFR from epithelial cells of established intestinal tumors in mice given AOM and
DSS did not reduce tumor size. EGFR signaling in myeloid cells promoted
activation of STAT3 and expression of survivin in intestinal tumor cells. Mice
with deletion of EGFR from myeloid cells developed more severe colitis after DSS
administration, characterized by increased intestinal inflammation and intestinal
barrier disruption, than control mice or mice with deletion of EGFR from
intestinal epithelial cells. EGFR-deficient myeloid cells in the colon of DSS
treated LysM-Cre; Egfrf/f mice had reduced expression of interleukin 6 (IL6), and
epithelial STAT3 activation was reduced compared with controls. Administration of
recombinant IL6 to LysM-Cre; Egfrf/f mice given DSS protected them from weight
loss and restored epithelial proliferation and STAT3 activation, compared with
administration of DSS alone to these mice. CONCLUSIONS: Increased expression of
EGFR in myeloid cells from the colorectal tumor stroma associates with tumor
progression and reduced survival time of patients with metastatic colorectal
cancer. Deletion of EGFR from myeloid cells, but not intestinal epithelial cells,
protects mice from colitis-induced intestinal cancer and ApcMin-dependent
intestinal tumorigenesis. Myeloid cell expression of EGFR increases activation of
STAT3 and expression of survivin in intestinal epithelial cells and expression of
IL6 in colon tissues. These findings indicate that expression of EGFR by myeloid
cells of the colorectal tumor stroma, rather than the cancer cells themselves,
contributes to tumor development.
PMID- 28400196
TI - Association of Ribonuclease T2 Gene Polymorphisms With Decreased Expression and
Clinical Characteristics of Severity in Crohn's Disease.
AB - BACKGROUND & AIMS: Variants in the tumor necrosis factor superfamily member 15
gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory
bowel disease (IBD). TL1A affects expression of multiple cytokines to promote
mucosal inflammation. Little is known about the TL1A-response pathways that
regulate cytokine expression. We investigated T-cell gene expression patterns to
determine the mechanisms by which TL1A regulates cytokine production, and whether
these associate with outcomes of patients with Crohn's disease (CD). METHODS:
Peripheral T cells isolated from normal donors were cultured with TL1A. We
performed gene expression profile analysis by RNA sequencing of subsets of
interferon gamma (IFNG)-producing and non-producing cells purified by flow
cytometry. Unsupervised hierarchical clustering analysis was used to identify
gene expression differences between these subsets. Ribonuclease T2 gene (RNASET2)
expression and methylation were assessed by quantitative trait loci analyses.
Clinical characteristics of patients (complications, resistance to therapy, and
recurrence time) were associated with single nucleotide polymorphisms in RNASET2.
We performed motif screening to identify polymorphisms that disrupt transcription
factor binding sites. Levels of RNASET2 were knocked down with small interfering
RNA in CD4+ T cells and the effect on protein expression was determined by
proteomic analysis and cytokine production. Cell aggregation was measured by flow
cytometry. RESULTS: We identified 764 genes with at least a 2-fold difference in
TL1A-mediated expression between IFNG-secreting and non-secreting T cells (P < 1
* 10-5). Many of these genes were located near IBD susceptibility variants.
RNASET2 was the only IBD risk-associated gene with >5-fold down-regulation in the
IFNG-secreting subset. RNASET2 disease risk variants were associated with
decreased expression in peripheral and mucosal tissues and DNA hypermethylation
in CD patients requiring surgical intervention. RNASET2 disease risk variants
were associated in CD patients with more complicated disease or resistance to
therapy, defined in part by failed response to treatment, increased length of
intestinal resection, shorter time to repeat surgery, and high Rutgeerts score
(>2) in postoperative endoscopy. The RNASET2 variant rs2149092 was predicted to
disrupt a consensus binding site for the transcription factor ETS within an
enhancer region. Expression of RNASET2 correlated with expression of ETS. RNASET2
knockdown in T cells increased expression of IFNG and intercellular adhesion
molecule 1 (ICAM1) and induced T-cell aggregation. A blocking antibody against
(ILFA1), disrupting the lymphocyte function-associated antigen 1-intercellular
adhesion molecule 1 interaction, reduced T-cell production of IFNG. CONCLUSIONS:
We identified decreased expression of RNASET2 as a component of TL1A-mediated
increase in production of IFNG and as a potential biomarker for patients with
severe CD. Further study of the role of RNASET2 in regulating mucosal
inflammation may lead to development of novel therapeutic targets.
PMID- 28400198
TI - Vitamin B12-Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12
Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular
Injection.
AB - This study aimed to formulate and evaluate vitamin B12-loaded buccal mucoadhesive
hydrogel films. Various film formulations were prepared using chitosan and
polyvinyl alcohol. The prepared films were characterized for thickness, weight
variation, drug content, percentage moisture uptake and moisture content, surface
pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12
bioavailability from the optimized formulation was studied on rabbits by the aid
of enzyme-linked immunosorbent assay. Neuroton(r) I.M. injection was used for
comparison. The films had acceptable mechanical and mucoadhesion properties. The
percentages of moisture content of the optimized formulation were 3.2 +/- 0.95,
whereas the percentage drug released was 98.59 +/- 1.41% at the end of 40 min.
FTIR revealed the incidence of drug/polymer interaction. Differential scanning
calorimetry revealed the possibility of the dispersion of cyanocobalamin in a
molecular state with complete amorphization in the polymers. The estimated AUC0
8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the
optimized formulation compared with the marketed I.M. injection. These findings
warrant that vitamin B12 buccal film formulation can be considered as an
effective alternative portal with noninvasive and more convenient characteristics
compared with the I.M. injection dosage form.
PMID- 28400197
TI - Cutaneous Penetration-Enhancing Effect of Menthol: Calcium Involvement.
AB - Menthol is a naturally occurring terpene used as a penetration enhancer in
topical and transdermal formulations. Literature shows a growing interest in
menthol's interactions with the transient receptor potential melastatin 8. A
decrease in extracellular Ca2+ due to the activation of the transient receptor
potential melastatin 8 receptor produces inhibition of E-cadherin expression that
is responsible for cell-cell adhesion. Because calcium is present in the entire
epidermis, the purpose of this study is to evaluate whether the aforementioned
properties of menthol are also related to its penetration-enhancing effects. We
formulated 16 gels: (i) drug-alone (diphenhydramine or lidocaine), (ii) drug with
menthol, (iii) drug, menthol, and calcium channel blocker (CCB; verapamil or
diltiazem), and (iv) drug and CCB. In vitro studies showed no effect of the CCB
on the release of the drugs either with or without menthol. In vivo experiments
were performed for each drug/menthol/CCB combination gel by applying 4
formulations on a shaved rabbit's dorsum on the same day. Dermis concentration
profiles were assessed with microdialysis. The gels containing menthol showed
higher penetration of drugs than those without whereas the addition of the CCB
consistently inhibited the penetration-enhancing effects of menthol. In summary,
these findings strongly support the involvement of calcium in the penetration
enhancing effect of menthol.
PMID- 28400199
TI - Viruses of managed alfalfa leafcutting bees (Megachille rotundata Fabricus) and
honey bees (Apis mellifera L.) in Western Canada: Incidence, impacts, and
prospects of cross-species viral transmission.
AB - We examined whether alfalfa leafcutting bees (ALCB, Megachille rotundata)
experienced a higher incidence of seven viruses commonly found honey bees (Apis
mellifera) when placed alongside honey bees for hybrid canola seed pollination.
Although two viruses - sacbrood virus (SBV) and deformed wing virus (DWV) - were
detected in ALCB adults, their presence appeared independent of whether honey
bees were present in the same field or not. A further survey of viruses among
ALCB adults in three different alfalfa seed growing regions in Western Canada
confirmed the ubiquity of sacbrood virus (SBV) as well as the infrequent presence
of acute bee paralysis virus (ABPV), both of which had not been previously
reported on ALCB. Moreover, SBV and ABPV were detected in the cocoon stage and
only in one region. Co-infection among pools of ALCB adults with both of these
viruses was more closely correlated with decreasing levels of cocoon viability
than infection levels in cocoons themselves. This research suggests ongoing viral
transmission between honey bees and ALCB in the same fields is likely low but
that co-infection with these viruses may lower ALCB productivity.
PMID- 28400200
TI - Thalamic DBS with a constant-current device in essential tremor: A controlled
clinical trial.
AB - INTRODUCTION: This study of thalamic deep brain stimulation (DBS) investigated
whether a novel constant-current device improves tremor and activities of daily
living (ADL) in patients with essential tremor (ET). METHODS: A prospective,
controlled, multicenter study was conducted at 12 academic centers. We
investigated the safety and efficacy of unilateral and bilateral constant-current
DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with
essential tremor whose tremor was inadequately controlled by medications. The
primary outcome measure was a rater-blinded assessment of the change in the
target limb tremor score in the stimulation-on versus stimulation-off state six
months following surgery. Multiple secondary outcomes were assessed at one-year
follow-up, including motor, mood, and quality-of-life measures. RESULTS: 127
patients were implanted with VIM DBS. The blinded, primary outcome variable (n =
76) revealed a mean improvement of 1.25 +/- 1.26 points in the target limb tremor
rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary
outcome variables at one year revealed significant improvements (p <= 0.001) in
quality of life, depression symptoms, and ADL scores. Forty-seven patients had a
second contralateral VIM-DBS, and this group demonstrated reduction in second
sided tremor at 180 days (p < 0.001). Serious adverse events related to the
surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device
explantation (n = 3). CONCLUSION: Unilateral and bilateral constant-current VIM
DBS significantly improves upper extremity tremor, ADL, quality of life, and
depression in patients with severe ET.
PMID- 28400201
TI - Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK)
exert a strong anti-herpesviral activity.
AB - Infection with human cytomegalovirus (HCMV) is a serious medical problem,
particularly in immunocompromised individuals and neonates. The success of
(val)ganciclovir therapy is hampered by low drug compatibility and induction of
viral resistance. A novel strategy of antiviral treatment is based on the
exploitation of cell-directed signaling, e. g. pathways with a known relevance
for carcinogenesis and tumor drug development. Here we describe a principle for
putative antiviral drugs based on targeting dual-specificity tyrosine
phosphorylation-regulated kinases (DYRKs). DYRKs constitute an evolutionarily
conserved family of protein kinases with key roles in the control of cell
proliferation and differentiation. Members of the DYRK family are capable of
phosphorylating a number of substrate proteins, including regulators of the cell
cycle, e.g. DYRK1B can induce cell cycle arrest, a critical step for the
regulation of HCMV replication. Here we provide first evidence for a critical
role of DYRKs during viral replication and the high antiviral potential of DYRK
inhibitors (SC84227, SC97202 and SC97208, Harmine and AZ-191). Using established
replication assays for laboratory and clinically relevant strains of HCMV,
concentration-dependent profiles of inhibition were obtained. Mean inhibitory
concentrations (EC50) of 0.98 +/- 0.08 MUM/SC84227, 0.60 +/- 0.02 MUM/SC97202,
6.26 +/- 1.64 MUM/SC97208, 0.71 +/- 0.019 MUM/Harmine and 0.63 +/- 0.23 MUM/AZ
191 were determined with HCMV strain AD169-GFP for the infection of primary human
fibroblasts. A first analysis of the mode of antiviral action suggested a block
of viral replication at the early-late stage of HCMV gene expression. Moreover,
rhesus macaque cytomegalovirus (RhCMV), varicella-zoster virus (VZV) and herpes
simplex virus (HSV-1) showed a similarly high sensitivity to these compounds.
Thus, we conclude that DYRK signaling represents a promising target pathway for
the development of novel anti-herpesviral strategies.
PMID- 28400202
TI - Genetic Variation in Kruppel like Factor 15 Is Associated with Left Ventricular
Hypertrophy in Patients with Type 2 Diabetes: Discovery and Replication Cohorts.
AB - Left ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in
type 2 diabetes and is associated with the development of heart failure. The
transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart
and acts as a repressor of cardiac hypertrophy in experimental models. This study
investigated if KLF15 gene variants were associated with LVH in type 2 diabetes.
In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known
cardiac disease were prospectively recruited for a transthoracic
echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and
genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915,
rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated
in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS)
type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated
in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment
for age, gender, body mass index (BMI) and hypertension, and with adjusted septal
(P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of
patients. Over a median follow up of 5.6years, there were 22 (7%) first heart
failure hospitalizations. The adjusted risk of heart failure hospitalization was
5.5-fold greater in those with LVH and the rs9838915 A allele compared to those
without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6-18.6), P=0.006). The
association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort.
We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in
patients with type 2 diabetes, and replicated these findings in a large
independent cohort. Studies are needed to characterize the functional importance
of these results, and to determine if the SNP rs9838915 A allele is associated
with LVH in other high risk patient cohorts.
PMID- 28400203
TI - Transcriptomic and genomic features of invasive lobular breast cancer.
AB - Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer
(ILC) is the second most common histological subtype of breast cancer after
invasive ductal breast cancer (IDC). Understanding ILC biology, which differs
from IDC in terms of clinical presentation, treatment response, relapse timing
and patterns, is essential in order to adopt novel, disease-specific management
strategies. While the contribution of the histological subtypes to tumour biology
has been poorly investigated and acknowledged in the past, recently several
major, independent efforts have led to the assembly and molecular
characterization of well-annotated ILC case sets. In this review, we provide a
critical overview of the literature exploring ILC, through comprehensive and
multiomic methods. The first part specifically focuses on ILC transcriptomic
features by reviewing the intrinsic molecular subtypes, the application of gene
expression scores for the prediction of recurrence, and the identification of
gene expression subtypes. The second part describes the main research efforts
that lead to the identification of the genomic landscape of ILC, with a special
focus to findings that differentiate ILC from IDC and carry potential clinical
relevance.
PMID- 28400204
TI - Computed navigated total knee arthroplasty compared to computed tomography scans.
AB - BACKGROUND: Successful total knee arthroplasty (TKA) includes accurate alignment.
Controversy remains as to whether computer-navigated TKA improves the overall
result and clinical outcome. Our aim is to compare the limb alignment and
prosthesis positioning according to the pre- and postoperative computed
tomography (CT) scans with the data collected from the navigation system.
METHODS: We compared the pre- and postoperative limb alignments and prosthesis
alignment provided by the Orthopilot navigation system, Aesculap(r), with CT
scans measured by the Traumacad(r) software of 70 TKAs. RESULTS: A positive
correlation with statistical significance (P=0.00001, r=0.874) between the
navigation system data and the CT images was found. Mean femoral cut was five
degrees (valgus), and mean tibial cut was one degree (varus). Our study revealed
that the navigation system assisted the surgeon to implant the prosthesis at a
good acceptable alignment. CONCLUSION: We found that the navigation system is
accurate and correlates to the pre- and postoperative CT scans. Furthermore, the
navigation system can assist the surgeon to achieve good limb alignment and
cutting planes of the prosthesis.
PMID- 28400205
TI - Titanium dioxide aggregating nanoparticles induce autophagy and under-expression
of microRNA 21 and 30a in A549 cell line: A comparative study with cobalt(II,
III) oxide nanoparticles.
AB - The toxicity of TiO2 nanoparticles (NPs) is controversial, while it is widely
accepted for Co3O4 NPs. We present a comparative study concerning the uptake of
these NPs and their effect on cytoplasmic organelles and autophagy in a human
lung carcinoma cell line (A549), including assays on the expression of autophagy
related microRNAs. The NP accumulation caused a fast dose- and time-dependent
change of flow cytometry physical parameters particularly after TiO2 NP exposure.
The intracellular levels of metals confirmed it, but the Co concentration was ten
times higher than that of Ti. Both NPs caused neither necrosis nor apoptosis, but
cytotoxicity was mainly evident for Co3O4 NPs in the first 72h. TiO2 NPs caused
autophagy, contrarily to Co3O4 NPs. Furthermore, a significant and persistent
downregulation of miRNA-21 and miRNA-30a was observed only in TiO2 NPs-treated
cultures. The expression of miRNA-155 was similar for both NPs. Oxidative stress
was evident only for Co3O4 NPs, while both NPs perturbed endoplasmic reticulum
and p-53 expression. In conclusion, the oxidative stress caused by Co3O4 NPs can
influence energy homeostasis and hamper the ability to detoxify and to repair the
resulting damage, thus preventing the induction of autophagy, while TiO2 NPs
elicit autophagy also under sub-toxic conditions.
PMID- 28400206
TI - Elucidation of developmental patterns of marmoset corpus callosum through a
comparative MRI in marmosets, chimpanzees, and humans.
AB - The corpus callosum (CC) is present in all primate brains and is the major white
matter tract connecting the cerebral hemispheres for integration of sensory,
motor and higher-order cognitive information. The midsagittal area of the CC has
frequently been used as a sensitive biomarker of brain development. Although the
marmoset has been considered as an alternative non-human primate model for
neuroscience research, the developmental patterns of the CC have not been
explored. The present longitudinal study of magnetic resonance imaging
demonstrated that marmosets show a rapid increase of CC during infancy, followed
by a slow increase during the juvenile stage, as observed in chimpanzees and
humans. Marmosets also show a tendency toward a greater increase in CC during
late infancy and the juvenile stage, as observed in humans, but not in
chimpanzees. However, several differences between marmosets and humans were
identified. There was a tendency toward a greater maturation of the human CC
during early infancy. Furthermore, there was a tendency toward a greater increase
during late infancy and the juvenile stage in marmosets, compared to that
observed in chimpanzees and humans. These differences in the developmental
trajectories of the CC may be related to evolutional changes in social behavior.
PMID- 28400208
TI - Diesel exhaust particles (DEP) pre-exposure contributes to the anti-oxidant
response impairment in hCMEC/D3 during post-oxygen and glucose deprivation
damage.
AB - Recently, air pollution has been identified as a significant modifiable risk
factor to the increasing stroke burden. Diesel exhaust particles, characterized
by high polycyclic aromatic hydrocarbons content, constitute an important
component of outdoor air pollution and is known to cause oxidative stress, and
could therefore contribute to and exacerbate the effects of ROS in post-ischemic
injury. hCMEC/D3 cells have been submitted to 48h treatment with diesel exhaust
particles (25MUg/ml and 50MUg/ml, DEP50) or alternatively to 3h of oxygen and
glucose deprivation, followed by 1h of oxygen and glucose restoration. The
combined treatment consisted in 48h of diesel exhaust particles (25MUg/ml and
50MUg/ml, DEP50) followed by 3h of oxygen and glucose deprivation and 1h of
restoration. A panel of markers related to oxidative stress and inflammatory
responses, such as transcription factors (Nrf2 and HIF-1alpha), anti-oxidant
proteins (HO-1, SOD-1, Hsp70) and proteins potentially inducing further oxidative
stress or inflammation (Cyp1b1, iNOS, COX-2, TNF-alpha, IL-1alpha, IL-1beta, IL
8, VEGF), have been examined. Data obtained showed that diesel exhaust particles
and oxygen and glucose deprivation treatments alone elicited the antioxidants
response, each by means of a different transcription factor, while the combined
treatment led to a dysregulation of the antioxidant response during ischemic
injury reperfusion.
PMID- 28400207
TI - The Safety and Efficacy of Growth Hormone Secretagogues.
AB - INTRODUCTION: Growth hormone (GH) increases lean body mass, decreases fat mass,
increases exercise tolerance and maximum oxygen uptake, enhances muscle strength,
and improves linear growth. Long-term studies of GH administration offer
conflicting results on its safety, which has led to strict Food and Drug
Administration criteria for GH use. The potential drawbacks of exogenous GH use
are believed to be due in part to impaired regulatory feedback. AIM: To review
the literature on GH secretagogues (GHSs), which include GH-releasing peptides
and the orally available small-molecule drug ibutamoren mesylate. METHODS: Review
of clinical studies on the safety and efficacy of GHSs in human subjects. MAIN
OUTCOME MEASURE: Report on the physiologic changes from GHS use in human subjects
including its safety profile. RESULTS: GHSs promote pulsatile release of GH that
is subject to negative feedback and can prevent supra-therapeutic levels of GH
and their sequelae. To date, few long-term, rigorously controlled studies have
examined the efficacy and safety of GHSs, although GHSs might improve growth
velocity in children, stimulate appetite, improve lean mass in wasting states and
in obese individuals, decrease bone turnover, increase fat-free mass, and improve
sleep. Available studies indicate that GHSs are well tolerated, with some concern
for increases in blood glucose because of decreases in insulin sensitivity.
CONCLUSION: Further work is needed to better understand the long-term impact of
GHSs on human anatomy and physiology and more specifically in the context of a
diversity of clinical scenarios. Furthermore, the safety of these compounds with
long-term use, including evaluation of cancer incidence and mortality, is needed.
Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone
Secretagogues. Sex Med Rev 2018;6:45-53.
PMID- 28400209
TI - Astaxanthin attenuates glutamate-induced apoptosis via inhibition of calcium
influx and endoplasmic reticulum stress.
AB - Astaxanthin (AST) is a carotenoid that has been shown to have neuroprotective
effects. In this study, it was found that AST significantly inhibited glutamate
induced loss of cell viability and apoptosis. AST pretreatment attenuated
glutamate-induced activation of caspase-3, reduction of anti-apoptotic protein
Bcl-2, and increase of pro-apoptotic protein Bak. In addition, AST pretreatment
suppressed the production of intracellular reactive oxygen species. AST treatment
also prevented glutamate-induced increase of the level of activated p38 mitogen
activated protein kinase (MAPK), which has been shown to promote apoptotic
events. Furthermore, AST treatment greatly reduced the elevation of intracellular
calcium level induced by glutamate and inhibited the activity of calpain, a
calcium-dependent protease that plays an important role in mediating apoptosis
stimulated by calcium overload in cytoplasm. Both oxidative stress and calcium
overload can lead to endoplasmic reticulum (ER) stress. C/EBP-homologous protein
(CHOP) is a bZIP transcription factor that can be activated by ER stress and
promotes apoptosis. Here we found that AST attenuated glutamate-induced elevation
of CHOP and ER chaperone glucose-regulated protein (GRP78). Overall, these
results suggested that AST might protect cells against glutamate-induced
apoptosis through maintaining redox balance and inhibiting glutamate-induced
calcium influx and ER stress.
PMID- 28400211
TI - A SYBR(r) Green-based real-time PCR method for improved detection of mcr-1
mediated colistin resistance in human stool samples.
AB - OBJECTIVES: The aim of this study was to design a rapid and sensitive real-time
PCR (rt-PCR) method for colistin resistance mcr-1 gene detection in human faecal
samples. METHODS: Stools (n=88) from 36 volunteers were analysed. To isolate mcr
1-producing Enterobacteriaceae, samples were enriched overnight in Luria-Bertani
(LB) broth containing 2mg/L colistin and were then plated on selective agar
plates with 4mg/L colistin. A SYBR(r) Green-based rt-PCR targeting mcr-1 was then
designed. For method validation and to establish the limit of detection (LOD),
total DNA was extracted from mcr-1-negative and mcr-1-positive Escherichia coli.
rt-PCR was also performed with DNA extracted from 88 native stools and after
enriching them in LB broth containing colistin. RESULTS: Based on the culture
approach, three unique volunteers resulted colonised with mcr-1-harboring E. coli
strains. For culture isolates, rt-PCR exhibited a LOD of 10 genomic
copies/reaction, with both sensitivity and specificity of 100%. Nevertheless,
when testing native stools, only two of the three mcr-1-positive specimens were
detected. However, after enrichment in LB broth containing colistin, the rt-PCR
was strongly positive for all culture-positive samples. The average cycle
threshold was 22, granting rapid and confident detection of positive specimens
within 30 cycles. No false positives were observed for the remaining 85 culture
negative specimens. CONCLUSIONS: A rapid rt-PCR for detection of mcr-1 from stool
specimens was developed. The detection rate was increased by testing selective
broth enrichments. This approach also has the advantage of concomitant isolation
of mcr-1-harboring strains for further antimicrobial susceptibility and genetic
testing.
PMID- 28400210
TI - Derepression of SaPIbov1 Is Independent of phiNM1 Type 2 dUTPase Activity and Is
Inhibited by dUTP and dUMP.
AB - Staphylococcus aureus is an opportunistic human pathogen able to transfer
virulence genes to other cells through the mobilization of S. aureus
pathogenicity islands (SaPIs). SaPIs are derepressed and packaged into phage-like
transducing particles by helper phages like 80alpha or phiNM1. Phages 80alpha and
phiNM1 encode structurally distinct dUTPases, Dut80alpha (type 1) and DutNM1
(type 2). Both dUTPases can interact with the SaPIbov1 Stl master repressor,
leading to derepression and mobilization. That two structurally distinct dUTPases
bind the same repressor led us to speculate that dUTPase activity may be
important to the derepression process. In type 1 dUTPases, Stl binding is
inhibited by dUTP. The purpose of this study was to assess the involvement of
dUTP binding and dUTPase activity in derepression by DutNM1. DutNM1 activity
mutants were created and tested for dUTPase activity using a novel NMR-based
assay. We found that all DutNM1 null activity mutants interacted with the
SaPIbov1 Stl C-terminal domain, formed DutNM1-Stl heterodimers, and caused the
release of the Pstr promoter. However, promoter release was inhibited in the
presence of dUTP or dUMP. We tested two phiNM1 mutant phages that had null enzyme
activity and found that they could still mobilize SaPIbov1. These results show
that only the apo form of DutNM1 is active in Stl derepression and that dUTPase
activity is not necessary for the mobilization of SaPIbov1 by DutNM1.
PMID- 28400212
TI - Susceptibility to 18 drugs and multidrug resistance of Arcobacter isolates from
different sources within the Czech Republic.
AB - OBJECTIVES: Arcobacter spp. are considered to be potential foodborne pathogens,
and consumption of contaminated food containing these bacteria could endanger
human and animal health. Arcobacter butzleri and Arcobacter cryaerophilus are the
species most frequently isolated from food of animal origin and from other
samples. The aim of this study was to evaluate the susceptibility of arcobacters
isolated in the Czech Republic. No information about antibiotic susceptibility
and multidrug resistance of arcobacters isolated in the Czech Republic is
available in the literature before now. METHODS: The antimicrobial resistance of
A. butzleri (n=80) and A. cryaerophilus (n=20) isolated from meat of animal
origin, water sources and clinical samples was examined by the disk diffusion
method. RESULTS: Arcobacters were resistant to one or more antimicrobial agents
in 99% (99/100) of tested isolates. Most of the Arcobacter isolates were
resistant to beta-lactam antibiotics, i.e. ampicillin (81.0%),
amoxicillin/clavulanic acid (28.0%), cefalotin (73.0%) and aztreonam (93.0%).
Arcobacters were also frequently resistant to lincosamides, i.e. clindamycin
(98.0%). Of the aminoglycosides, amikacin, gentamicin and tobramycin were
evaluated to be the most effective antibiotics among those tested against
arcobacters. CONCLUSIONS: These results demonstrate substantial resistance in
Arcobacter isolates to 18 antimicrobial agents commonly used in medical and
veterinary medicine. Multidrug resistance was found in 93.8% (75/80) of A.
butzleri isolates and 70.0% (14/20) of A. cryaerophilus isolates.
PMID- 28400213
TI - Investigation of 8-OHdG, CYP1A, HSP70 and transcriptional analyses of antioxidant
defence system in liver tissues of rainbow trout exposed to eprinomectin.
AB - Eprinomectin (EPM), a member of avermectin family, is a semi-synthetic
antibiotic. It has been known that avermectin family enters the aquatic
environments and adversely affects the aquatic organisms. Effects of EPM is fully
unknown in aquatic organisms especially fish, thus the aim of the present study
was to investigate transcriptional changes (sod, cat, gpx) and activities of some
antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and
catalase (CAT) and malondialdehyde (MDA) levels, oxidative DNA damage (8-hydroxy
2-deoxyguanosine (8-OHdG)) and transcriptional changes of heat shock protein 70
(HSP70), and cytochromes P4501A (CYP1A) in liver tissues of rainbow trout exposed
to sublethal EPM concentration (0.001 MUg/L, 0.002 MUg/L, 0.01 MUg/L, 0.05 MUg/L)
for 24 h, 48 h, 72 h and 96 h. The decrease in antioxidant enzyme (SOD, CAT and
GPx) activity, transcriptional changes (sod, cat, gpx, HSP70 and CYP1A genes) and
increase in MDA level and activity of 8-OHdG in a dose-time-dependent manner in
the liver of rainbow trout were observed. The down-regulated of antioxidant (sod,
cat and gpx), HSP70 and CYP1A obviously, the severity of which increased with the
concentration of EPM and exposure time. The results imply that EPM could induce
oxidative damage to the liver tissue of rainbow trout. The information presented
in this study is helpful to understand the mechanism of veterinary
pharmaceuticals-induced oxidative stress in fishes.
PMID- 28400214
TI - Characterization of PmSpatzle 1 from the black tiger shrimp Peneaus monodon.
AB - Spatzle is a signaling ligand in innate immune response that signals pathogenic
infection via Toll receptor and Toll pathway into the cells for the synthesis of
antimicrobial proteins. Herein, three PmSpatzle isoforms were identified in
Penaeus monodon, namely PmSpz1, 2 and 3. The PmSpz1 was chosen for detailed
study. The PmSpz1 gene was expressed in all nine tissues tested including the
hemocytes, stomach, hepatopancreas, gill, lymphoid tissue, eyestalk, muscle,
intestine and heart. Its expression was up-regulated upon white spot syndrome
virus (WSSV) infection. Western blot analysis of hemolymph showed that the PmSpz1
mostly existed as a cleaved active form awaiting to activate the Toll pathway.
Injection of a recombinant PmSpz1 rendered the shrimp less susceptible to the
WSSV infection. Injection of a recombinant active form of PmSpz1 into a normal
shrimp activated the synthesis of crustinPm1, crustinPm7, ALFPm3, penaeidin3 but
not penaeidin5 indicating that the expression of all antimicrobial proteins but
not penaeidin5 was under the regulation of Toll pathway.
PMID- 28400215
TI - Levamisole enhances the innate immune response and prevents increased cortisol
levels in stressed pacu (Piaractus mesopotamicus).
AB - We analyzed the effects of levamisole on stress and the innate immune responses
of pacu (Piaractus mesopotamicus). A total of 300 fish (180 +/- 1.27 g) were fed
a diet containing levamisole hydrochloride (LHC) for 15 days, then distributed
into the following groups: T0 (control group); T1 (100), T2 (150), T3 (300) and
T4 (500) mg kg-1 LHC (15 fish per group and four replicates per treatment). After
this, fish (n = 8 per treatment) were exposed to air for three minutes to
simulate stress conditions and were then challenged with the bacterium Aeromonas
hydrophila to stimulate the immune system. Fish were sampled at 1, 3 and 24 h
after bacterial inoculation to measure plasma cortisol and glucose
concentrations, the leukocyte respiratory burst (LRB), hemolytic activity of the
complement system (HAC50) and serum lysozyme activity (SLA). LHC attenuated the
increase in plasma cortisol at 1 h (500 mg kg-1) and 3 h (300 mg kg-1) after air
exposure and bacterial inoculation compared to control fish. The highest glucose
concentrations were observed at 1 and 3 h after stress, which then returned to
initial levels after 24 h, without any effect of LHC. The LHC 100 mg kg-1 dose
increased LRB 1 h after inoculation and activated the HAC50 3 h later. At 24 h,
all LHC concentrations increased the HAC50. SLA was reduced after inoculation,
throughout the experimental period, without an effect of levamisole. Our results
indicate that the oral administration of levamisole for 15 days modulated
circulating cortisol levels during the stress response and improved the innate
immune response against A. hydrophila infection in pacu.
PMID- 28400216
TI - High mortality rates after both open surgical and endovascular thoracic aortic
interventions in patients with end-stage renal disease.
AB - BACKGROUND: Morbidity and mortality have improved with the evolution of
endovascular techniques (thoracic endovascular aortic repair [TEVAR]) for
thoracic aortic disease, but results after aortic intervention in patients with
end-stage renal disease (ESRD) remain unclear. The objective of this study was to
evaluate outcomes of open and endovascular descending thoracic aortic repair in
dialysis-dependent patients. METHODS: We identified 352 patients with ESRD on
dialysis undergoing open repair (n = 136) or TEVAR (n = 216) of the thoracic
aorta from 2005 to 2008 using the United States Renal Data System database. Acute
presentation was defined as ruptured aneurysm, dissection, or traumatic injury;
all other interventions were considered elective. End points were 30-day
mortality, overall survival, rates of perioperative complications, and procedural
trends over time. Between-group comparisons and survival analysis used standard
statistical methods. Logistic regression and Cox regression were performed using
multivariate analysis. RESULTS: TEVAR subjects were older than those undergoing
open repair (68.2 +/- 11.5 vs 60.8 +/- 13.2 years; P < .001); no other
demographics differed. There were 303 patients who had thoracic or
thoracoabdominal aneurysms; 47 (13.4%) were ruptured on presentation. There were
44 patients (12.5%) who had aortic dissection and 5 (1.4%) with aortic trauma.
Overall 30-day mortality was 21.3% (n = 75), and it was greater for open repair
(n = 41 [30.1%]) than for TEVAR (n = 34 [15.7%]; P = .002). Elective 30-day
mortality for open repair (n = 27 [29.3%]) was also greater than for TEVAR (n =
24 [14.3%]; P = .005). Those with acute presentation trended toward higher
mortality for open repair (n = 14 [31.8%] vs n = 10 [15.7%]; P = .17).
Respiratory failure was higher for open repair (n = 69 [50.7%] vs n = 56 [25.9%];
P < .001); postoperative stroke was higher with TEVAR (n = 21 [9.7%] vs n < 10
[<7%]; P = .02). Estimated 1-year survival was 50% and did not differ between
groups (44% for open repair, 53% for TEVAR). In multivariate analysis, TEVAR
decreased odds of 30-day mortality compared with open repair (odds ratio, 0.41;
95% confidence interval, 0.24-0.71) but failed to demonstrate long-term survival
advantage. CONCLUSIONS: In ESRD patients, TEVAR provides short-term mortality
benefits compared with open repair, but long-term mortality remains high
regardless of treatment modality. Elective intervention for thoracic aortic
disease in this population remains high risk and should be approached with
caution.
PMID- 28400217
TI - Korea, M*A*S*H, and the accidental pioneers of vascular surgery.
PMID- 28400218
TI - Outcomes of the Japanese multicenter Viabahn trial of endovascular stent grafting
for superficial femoral artery lesions.
AB - OBJECTIVE: The objective of this study was to assess 1-year safety, efficacy, and
invasiveness outcomes of endovascular stent grafting of symptomatic long lesions
(>=10 cm) in the superficial femoral artery (SFA) as a substitute for above-knee
open bypass surgery. METHODS: This prospective, multicenter (15 hospitals) study
assessed heparin-coated stent grafts for the treatment of long SFA lesions in
Japanese subjects with peripheral arterial disease. Inclusion criteria were
Rutherford category 2 to 5 symptoms (grade 5 without active infection), ankle
brachial index <=0.9, and color flow duplex ultrasound-assessed SFA lesions with
cumulative length >=10 cm and >=50% stenosis. Main efficacy and safety outcomes
were primary assisted patency and adverse events, respectively. Secondary
outcomes included primary patency using the surgical bypass definition, that is,
blood flow through a device without requiring target lesion revascularization
(TLR) to maintain or to restore flow. For comparison with prior endovascular
studies, primary patency-interventional was defined as peak systolic velocity
ratio <2.5 without TLR in treated lesions. Other outcomes included freedom from
TLR and Vascular Quality of Life questionnaire scoring. General anesthesia
avoidance and hospitalization duration were compared with historical data from 68
consecutive patients (n = 51 Rutherford 2/3 claudicants and 17 Rutherford 4/5
subjects) who underwent above-knee bypass surgery at study sites between 2002 and
2012 and met study enrollment criteria. RESULTS: Of 103 enrollees (74.2 +/- 7.0
years old; 17.5% female; 97.1% claudicants), 100 subjects were evaluated through
postoperative 12 months. Average lesion length was 21.8 +/- 5.8 cm, and 65.7%
were totally occluded. The whole-cohort Kaplan-Meier estimated primary assisted
patency rate was 94.1% (95% confidence interval [CI], 87.3%-97.3%) at 12 months.
The primary patency-surgical rate was 92.1% (95% CI, 84.8%-96.0%), the primary
patency-interventional rate was 88.1% (95% CI, 80.0%-93.1%), and freedom from TLR
was 93.1% (95% CI, 86.1%-96.7%). Mean ankle-brachial index increased from 0.64 +/
0.12 to 0.98 +/- 0.12 at 1 month after intervention and 0.94 +/- 0 .17 at 12
months (P < .0001 at both follow-ups). Target vessel revascularization, major
amputation, or death did not occur through postoperative 30 days. No life- or
limb-threatening intraoperative or perioperative adverse events and no acute limb
ischemia cases were observed during follow-up. Vascular Quality of Life
questionnaire score increased from 58.6% +/- 15.7% to 72.9% +/- 18.6% at 12
months (P < .0001). No stent fractures were detected. No stent graft participant
required general anesthesia, and median postoperative hospital stay was 2.0 days
(mean, 3.4 +/- 2.9 days) in the Viabahn (W. L. Gore & Associates, Flagstaff,
Ariz) claudicant subgroup, values that were significantly lower than the 76.5%
general anesthesia rate (P < .0001) and 11.0 days median hospitalization stay
(mean, 12.7 +/- 5.3 days; P < .0001) in the 51 open bypass claudicant subjects.
CONCLUSIONS: Stent grafting appears to be a safe and less invasive alternative to
above-knee bypass surgery, providing 88% to 92% primary patency at 12 months in
long, complex lesions.
PMID- 28400219
TI - Comparative effectiveness of anticoagulation on midterm infrainguinal bypass
graft patency.
AB - OBJECTIVE: Therapeutic anticoagulation (AC) is used clinically for prolongation
of infrainguinal bypass patency, but evidence for the efficacy of this practice
is conflicting. The objective of our study was to determine the association of AC
with bypass graft primary patency. METHODS: Clinical and comorbid data of
patients undergoing infrainguinal bypass grafts to a below-knee target with at
least 1 year of follow-up performed from 2003 to 2015 were obtained from the
Society for Vascular Surgery Vascular Quality Initiative. Inverse propensity of
treatment-weighted Cox regression was used to assess the effect of AC on patency
in the total cohort while adjusting for clinical, operative, and comorbid
differences between treatment groups. Subgroup analyses of distal targets and
conduit type were performed. Perioperative complications were analyzed using
propensity-weighted logistic regression. RESULTS: We identified 7612 bypass
grafts with intact 1-year follow-up information from 2003 to 2015. The mean age
was 67.5 +/- 11.2 years; 30.5% (n = 2320) were female, and 28.6% (n = 2165) were
discharged on therapeutic AC. The anticoagulated group had a higher rate of
tibial, ankle, and pedal targets (52.1% [n = 1127] vs 47.6% [n = 2269]; P <
.001), had a greater use of non-single-segment vein conduits (44.3% [n = 951] vs
26.5% [n = 1426]; P < .001), and was more likely to have had a previous
ipsilateral bypass (27.2% [n = 589] vs 14.7% [n = 794]; P < .001) or stent (25.4%
[n = 550] vs 20.9% [n = 1130]; P < .001). Estimated unadjusted primary patency
was 70.8% +/- 0.6% at 1 year and lower for anticoagulated bypasses (66.9% +/-
1.2% vs 72.4% +/- 0.7%; P < .001). Propensity-weighted analysis showed no
significant association of AC with primary patency in the overall cohort (hazard
ratio [HR], 0.98; 95% confidence interval [CI], 0.86-1.11; P = .8) but
demonstrated a trend toward improvement of primary patency in those with a non
single-segment vein conduit to a below-knee popliteal target (HR, 0.85; 95% CI,
0.80-1.02; P = .09). AC was associated with significantly improved secondary
patency in those with prosthetic bypass grafts (HR, 0.77; 95% CI, 0.62-0.96; P =
.02) or prosthetic bypasses to an infrapopliteal target (HR, 0.72; 95% CI, 0.54
0.97; P = .02). Odds of postoperative wound complications were significantly
higher in those receiving AC (odds ratio, 1.33; 95% CI, 1.11-1.61; P = .002).
CONCLUSIONS: This study does not demonstrate a significant impact of therapeutic
AC on primary patency for infrainguinal bypass grafts. Treatment with AC may
benefit secondary patency in those with a prosthetic bypass, especially to an
infrapopliteal target, but at an increased risk of postoperative wound
complications.
PMID- 28400220
TI - Transvaginal Excision of an Eroded Sacrocolpopexy Mesh by Using Single-Incision
Laparoscopic Surgery Equipment.
AB - STUDY OBJECTIVE: To show a new technique of using single-incision laparoscopic
surgery (SILS) equipment in vaginal surgery to create a "pneumovagina." DESIGN:
Explanatory video demonstrating the technique and intraoperative findings.
SETTING: University hospital. PATIENT: The 68-year-old patient was referred with
a vaginal mesh erosion that resulted in abscess formation at the vaginal apex.
The patient was symptomatic with an increasingly foul-smelling vaginal discharge
for about 1 year. She had a laparoscopic sacrocolpopexy in a remote hospital 22
months before the current operation and had a total abdominal hysterectomy 15
years ago. The, patient's history was uneventful without dyspareunia,
incontinence or voiding difficulties, and she was otherwise content with the
sacrocolpopexy result. The local institutional review board granted exemption for
this publication. INTERVENTION: Frequently, pelvic organ prolapse can only be
effectively treated if the surgical procedure comprises support of the central
compartment. Laparoscopic sacrocolpopexy shows superior outcomes for this
indication, with success rates of up to 96%. However, a rare side effect of
laparoscopic sacrocolpopexy is mesh erosion, occurring in up to 2.4% [1]. These
erosions are usually treated laparoscopically [2]. In this video we show an
alternative route for excision of a symptomatic exposed mesh by using a
transvaginal approach: The SILS trocar is used vaginally for abscess irrigation
and mesh excision with minimally invasive instruments. MEASUREMENTS AND MAIN
RESULTS: For treatment of the abscess and removal of the exposed mesh, the SILS
trocar was placed vaginally, and laparoscopic instruments were used. The abscess
was incised, cleansed and irrigated, debrided, and the mesh excised. Because no
mesh material was exposed after excision, the vagina was not closed to avoid
creating a cavity with the risk of promoting reabscess formation, and secondary
wound healing was anticipated. Laparoscopy was used to confirm that no intra
abdominal lesion coexisted or occurred. There were no signs of further infection
of the residual mesh beyond the area exposed in the vagina. The patient's only
symptom was foul-smelling discharge, but no back pain or signs of systemic
inflammation were found. Knowing that foreign body (mesh) infection usually needs
to be treated by complete mesh removal, we did not have any clues of distant mesh
infection and counseled the patient that if reinfection occurred a second surgery
might be necessary. Nevertheless, we treated this patient with abscess drainage
and removal of large parts of the mesh. Thus, the operation was not extended to a
complete mesh excision to prevent major surgery and the risk of recurrent
prolapse. Particularly, the area of the mesh excision was inspected with the
rendezvous technique (light source vaginally, laparoscopic pelvic view with
laparoscopic light source switched off) to identify the area of mesh excision
from the intra-abdominal area. Sigmoid and rectum were distant to this area,
suggesting that no bowel lesion occurred. No complications occurred in the
postoperative course. In the follow-up visit 6 months postoperatively the patient
was asymptomatic, and the vaginal examination was uneventful with no recurrent
erosion. Although improved oversight and richness of detail achieved by the
vaginal SILS method is helpful in patients like our case with a suspended vaginal
vault, its costs need to be balanced against conventional vaginal approaches
(e.g., use of a Lonestar retractor). CONCLUSION: The SILS trocar and laparoscope
used (SILS Port; Covidien, New Haven, CT) vaginally provide a magnificent and
detailed view to allow for exact preparation by means of microinvasive
instruments in vaginal surgery, even more in patients with a suspended vaginal
vault where access to the apex can be tricky. The "pneumovagina" created by CO2
insufflation further helps to expose the vaginal apex. The rendezvous technique
can additionally be used to identify intra-abominal lesions.
PMID- 28400221
TI - Validation of a Self-Monitoring Tool for Use in Exercise Therapy.
AB - BACKGROUND: Aerobic exercise at a subsymptom heart rate has been recommended as
therapy for postconcussion syndrome. Assessing adherence with an accurate heart
rate-monitoring instrument is difficult, limiting the proliferation of large
scale randomized controlled trials. OBJECTIVE: To evaluate the validity of the
Fitbit Charge HR compared with electrocardiogram (EKG) to monitor heart rate
during a treadmill-based exercise protocol. DESIGN: A methods comparison study.
SETTING: Sports medicine research center within a tertiary care institution.
PARTICIPANTS: A convenience sample of 22 healthy participants (12 female) aged 18
26 years (mean age: 22 +/- 2 years). METHODS: Fitbit Charge HR heart rate
measurements were compared with EKG data concurrently collected while
participants completed the Buffalo Concussion Treadmill Test. MAIN OUTCOME
MEASURES: Agreement between Fitbit Charge HR and EKG was assessed by intraclass
correlation coefficients (ICC3,1), Bland-Altman limits of agreement, and percent
error. RESULTS: We observed a strong single-measure absolute agreement between
Fitbit Charge HR and EKG (intraclass correlation coefficient = 0.83; 95%
confidence interval 0.67-0.90). Fitbit Charge HR underestimated heart rate
compared with EKG (mean difference = -6.04 bpm; standard deviation = 10.40 bpm;
Bland-Altman 95% limits of agreement = -26.42 to 14.35 bpm). A total of 69.9% of
Fitbit heart rate measurements were within 10% error compared with EKG, and 91.5%
of all heart rate measurements were within 20% error. CONCLUSIONS: Although the
mean bias in measuring heart rate was relatively small, the limits of agreement
between the Fitbit Charge HR and EKG were broad. Thus, the Fitbit Charge HR would
not be a suitable option for monitoring heart rate within a narrow range. For the
purposes of postconcussion exercise therapy, the relatively inexpensive cost,
easy implementation, and low maintenance make Fitbit Charge HR a viable option
for assessing adherence to an exercise program when expensive clinical equipment
is unavailable. LEVEL OF EVIDENCE: II.
PMID- 28400222
TI - Self-Reported Health and Safety Awareness Improves Prediction of Level of Care
Needs in Veterans Discharged From a Postacute Unit.
AB - OBJECTIVES: To evaluate the differential value of a self-reported health and
safety awareness measure relative to other medical, psychosocial, and cognitive
factors in predicting level of care (LOC) needs after hospital discharge. DESIGN:
Retrospective medical record review. SETTING: Community living center postacute
care (CLC-PAC) unit at a Veterans Affairs hospital. PARTICIPANTS: A total of 175
veterans admitted to the Veterans Affairs hospital or directly to the CLC-PAC
from home. METHODS: Cognitive status was assessed with the Mini-Mental State
Examination, Digit Span Backward subtest, Trail Making Test (Part B), and Hopkins
Verbal Learning Test-Revised. Self-report of health and safety awareness was
measured with the Independent Living Scales Health and Safety (ILS-HS) subscale.
Additional demographic and admission-related variables were coded, along with
medical comorbidity, with the Charlson Comorbidity Index and depression using the
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision
Depression Checklist. MAIN OUTCOME MEASUREMENTS: Increased level of care was
collected from social work and occupational therapy notes and defined as
increased assistance with activities of daily living or nursing home placement
comparing prehospitalization with CLC-PAC discharge. RESULTS: A total of 19% (n =
34) of residents required increased LOC on CLC-PAC discharge. The ILS-HS was a
significant predictor of increased LOC above and beyond age and Mini Mental
Status Examination score; for each standard deviation decrease in ILS-HS, there
was an increased likelihood of greater LOC (odds ratio 0. 54, 95% confidence
interval 0.35-0.83). Other neuropsychological tests (memory, executive
functioning) did not significantly improve the model. CONCLUSIONS: The inclusion
of the ILS-HS to a standard cognitive screen (Mini Mental Status Examination) can
improve prediction of increased LOC. Although select aspects of memory and
executive functioning independently contribute to increased LOC prediction, the
ILS-HS likely measures a unique aspect of cognitive functioning that may be
specific to discharge planning needs in CLC-PAC residents. LEVEL OF EVIDENCE: II.
PMID- 28400223
TI - Acute Radial Neuropathy at the Spiral Groove Following Massage: A Case
Presentation.
AB - : Massage-related nerve injury is an uncommon, rarely reported complication. We
report an unusual case of radial nerve neuropathy at the spiral groove in a 58
year-old woman that resulted from a single episode of deep tissue massage.
Although the spiral groove is known as the most common site implicated in radial
nerve neuropathy, to our knowledge, there have not previously been any reports of
massage-related spiral groove radial nerve neuropathy. Electrodiagnostic and
ultrasound examinations were used to localize the nerve lesion at the spiral
groove and also to provide prognostic evaluation. Serial follow-ups demonstrated
concomitant improvement in clinical symptoms and electrodiagnostic parameters. A
near-total recovery was achieved after 6 months. This case presentation aims to
increase awareness and early recognition of massage-related nerve injuries. LEVEL
OF EVIDENCE: V.
PMID- 28400224
TI - New amides from seeds of Silybum marianum with potential antioxidant and
antidiabetic activities.
AB - Two new amide compounds, mariamides A and B (1-2), were obtained together with
fourteen known compounds from the seeds of milk thistle (Silybum marianum). Their
structures were established on the basis of extensive 1D and 2D NMR analyses, as
well as HR-ESI-MS data. Most of the compounds showed significant antioxidant
activities than positive control in ABTS and FRAP assays. However, only amide
compounds 1-4 showed moderate DPPH radical scavenging activity and compounds 7
and 16 showed the most potent activity against DPPH. Most of the compounds showed
moderate to stronger alpha-glucosidase inhibitory activities. Nevertheless, only
flavonoids showed strong PTP1B inhibitory activities. These results indicate a
use of milk thistle seed extracts as promising antioxidant and antidiabetic
agents.
PMID- 28400225
TI - PEGylated neuromedin U-8 shows long-lasting anorectic activity and anti-obesity
effect in mice by peripheral administration.
AB - Neuromedin U (NMU) is a neuropeptide found in the brain and gastrointestinal
tract. The NMU system has been shown to regulate energy homeostasis by both a
central and a peripheral mechanism. Peripheral administration of human NMU-25 was
recently shown to inhibit food intake in mice. We examined the possibility that
other NMU-related peptides exert an anorectic activity by intraperitoneal (i.p.)
administration. We found that rat NMU-23 and its structurally-related peptide rat
neuromedin S (NMS) significantly reduced food intake in lean mice, whereas NMU-8,
an active fragment of the octapeptide sequence conserved in porcine, human and
mouse NMU, had no effect. When rat NMU-23, NMU-8, and rat NMS were covalently
conjugated to polyethylene glycol (PEG) (PEGylation) at the N-terminus of these
peptides, PEGylated NMU-8 showed the most long-lasting and robust anorectic
activity. The exploration of the linker between NMU-8 and PEG using hetero
bifunctional chemical cross-linkers led to an identification of PEGylated NMU-8
analogs with higher affinity for NMU receptors and with more potent anorectic
activity in lean mice. The PEGylated NMU-8 showed potent and robust anorectic
activity and anti-obesity effect in diet-induced obesity (DIO) mice by once-daily
subcutaneous (s.c.) administration. These results suggest that PEGylated NMU-8
has the therapeutic potential for treatment of obesity.
PMID- 28400226
TI - In-vitro effect of human cathelicidin antimicrobial peptide LL-37 on dengue virus
type 2.
AB - Human Cathelicidin antimicrobial peptide LL-37 is known to have antiviral
activity against many viruses. In the present study, we investigated the in-vitro
effect of LL-37 on dengue virus type 2 (DENV-2) infection and replication in Vero
E6 cells. To study the effect of pretreatment of virus or cells with LL-37, the
virus was pretreated with different concentrations of LL-37 (2.5MUM-15MUM) or
scrambled (Scr) LL-37(5MUM-15MUM) and used for infection or the cells were first
treated with LL-37 and infected. To study the effect of LL-37 post infection
(PI), the cells were infected first followed by addition of LL-37 to the culture
medium 24h after infection. In all conditions, after the incubation, the culture
supernatant was assessed for viral RNA copy number by real time RT-PCR,
infectious virus particles by focus forming unit assay (FFU) and non structural
protein 1 (NS1) antigen levels by ELISA. Percentage of infection was assessed
using immunoflourescence assay (IFA). The results revealed that pretreatment of
virus with 10-15MUM LL-37 significantly reduced its infectivity as compared to
virus control (P<0.0001). Moreover, pretreatment of virus with 10-15MUM LL-37
significantly reduced the levels of viral genomic RNA and NS1 antigen (P<0.0001).
Treatment of virus with 10-15MUM LL-37 resulted in two to three log reduction of
mean log10 FFU/ml as compared to virus control (P<0.0001). Treatment of the virus
with scrambled LL-37 had no effect on percentage of infection and viral load as
compared to virus control cultures (P>0.05). Pretreatment of cells before
infection or addition of LL-37 to the culture 24h PI had no effect on viral load.
Molecular docking studies revealed possible binding of LL-37 to both the units of
DENV envelope (E) protein dimer. Together, the in-vitro experiments and in-silico
analyses suggest that LL-37 inhibits DENV-2 at the stage of entry into the cells
by binding to the E protein. The results might have implications for prophylaxis
against DENV infections and need further in-vivo studies.
PMID- 28400227
TI - Effectiveness of Intraventricular Endoscopic Lamina Terminalis Fenestration in
Comparison with Standard ETV: Systematic Review of Literature.
AB - BACKGROUND: Endoscopic third ventriculostomy is a consolidated technique for the
treatment of hydrocephalus. Despite its effectiveness and feasibility, several
technical limitations about its use in certain situations have been described.
Lamina terminalis-endoscopic third ventriculostomy (LT-ETV) has been proposed as
an alternative technique. Authors systematically reviewed the literature in order
to define the effectiveness and limits in comparison with standard ETV. METHODS:
This systematic review followed the PRISMA (Preferred Reporting Items for
Systematic Reviews and Meta-Analyses) statement. It has also been registered with
the PROSPERO International Prospective Register of Systematic Reviews
(CRD42016041596). MEDLINE, Web of Knowledge, and EMBASE were independently
searched. RESULTS: Seven studies were found to be eligible. A case of ours was
added to the series, totaling 41 patients (mean patient age +/- SD was 21.6 +/-
20.7 years). Endoscopic findings leading surgeons to perform LT-ETV were abnormal
ventricular anatomy (24, 57%), inadequate/insufficient interpeduncular
subarachnoid space (11, 26%), a combination of both (5, 12%), and intraoperatory,
unsatisfactory third ventricle floor fenestration (2, 5%). Most common
pathologies were neurocysticercosis (12, 28.57%), aqueductal stenosis (8, 19%),
tuberculous meningitis (4, 9.52%), and medulloblastoma (3, 7.14%). A flexible
endoscope was the most used device (36 procedures, 86%), while not determining a
statistical relevant diminution of complications in comparison with a rigid
endoscope (P = 1.0). An overall success rate of 69% was registered, increasing to
89% if just the first year of follow-up was considered. CONCLUSIONS: LT-ETV can
be considered a successful technical option when standard ETV cannot be
performed, although more complex cerebrovascular anatomy is involved. Therefore
we suggest that lateral terminalis fenestration is a valid technical option in
experienced hands.
PMID- 28400228
TI - Keen's Point for External Ventricular Drainage in Traumatic Brain Injury
Patients: An Uncommon Indication for An Old Technique.
AB - BACKGROUND: In cases of severe traumatic brain injury, cerebrospinal fluid (CSF)
diversion though an external ventricular drain (EVD) is a proven method to assist
in the control of elevated intracranial pressure. Under normal circumstances, the
EVD is placed in a frontal location. However, in cases of multifocal intracranial
injury and swelling, collapse of the frontal horns of the lateral ventricles
leads to frequent failure of frontal CSF drainage. In this series we describe the
utility of the Keen's point EVD as a safe alternative to maintain continuous CSF
diversion for patients in whom frontal drainage is not feasible. CASE
DESCRIPTIONS: Three patients (ages 30-46 years) with diffuse intracranial injury
following severe trauma were admitted to our neurointensive care unit. One of
these patients had decompressive craniectomy before transfer, while the other 2
patients did not undergo any surgical procedures. Each of these patients had
severe refractory elevation of intracranial pressure and significant frontal
swelling, ultimately necessitating bedside placement of a Keen's point EVD.
CONCLUSIONS: In all cases, we were able to reliably maintain continuous CSF
diversion for an extended period of time. There was 1 mortality due to the
severity of initial injuries. In the remaining 2 patients, intracranial pressure
was able to be normalized following placement of the Keen point EVD. The Keen
point EVD is a viable option to maintain continuous CSF drainage in patients with
diffuse intracranial injury and should be considered in patients whom a frontal
EVD cannot reliably maintain continuous drainage of CSF.
PMID- 28400229
TI - Clinical Features and Surgical Outcomes in Patients with Cerebellopontine Angle
Hemangioblastomas: Retrospective Series of 23 Cases.
AB - OBJECTIVES: Hemangioblastomas in the cerebellopontine angle (CPA) are uncommon
and have rarely been reported. They may be easily misdiagnosed because of the
atypical location and clinical and imaging features. The present study aimed to
characterize clinical and radiologic features, treatment strategies, and outcomes
in these rare lesions and to investigate various factors that may affect
postoperative outcomes. METHODS: The medical records of patients with CPA
hemangioblastomas who underwent surgery from 2003-2016 at the West China Hospital
were reviewed retrospectively and statistically analyzed. RESULTS: Twenty-three
patients (14 males and 9 females) presented with CPA hemangioblastomas. Eight
patients (34.8%) had von Hippel-Lindau (VHL) syndrome. Gross total resection was
achieved in 22 patients (95.6%). The mean follow-up was 45.1 +/- 36.2 months
(range 3-144 months). After surgery, the symptoms improved in 18 cases (78.3%),
remained unchanged in 3 cases (13%), and were aggravated in 2 cases (8.7%). Four
patients showed local recurrence during follow-up (17.4%). Patients with cystic
hemangioblastomas had a better neurologic improvement (P = 0.041) compared with
patients with solid tumors. Furthermore, patients with maximal diameter of tumors
>3 cm (P = 0.035) or solid tumors (P = 0.018) showed a higher incidence of
postoperative complications. The local recurrence was correlated with VHL disease
(P = 0.027). CONCLUSIONS: Although hemangioblastomas of the CPA are challenging
lesions to treat surgically, they can be removed safely when these lesions are
appropriately diagnosed and treated. Patients with VHL disease are more likely to
have a local recurrence. A regular follow-up is recommended to detect the local
and distant recurrence, even if the clinical course is benign and the tumor is
totally resected.
PMID- 28400230
TI - Investigation of the inhibitory mechanism of apomorphine against MDM2-p53
interaction.
AB - Mirror-image screening using d-proteins is a powerful approach to provide mirror
image structures of chiral natural products for drug screening. During the course
of our screening study for novel MDM2-p53 interaction inhibitors, we identified
that NPD6878 (R-(-)-apomorphine) inhibited both the native l-MDM2-l-p53
interaction and the mirror-image d-MDM2-d-p53 interaction at equipotent doses. In
addition, both enantiomers of apomorphine showed potent inhibitory activity
against the native MDM2-p53 interaction. In this study, we investigated the
inhibitory mechanism of both enantiomers of apomorphine against the MDM2-p53
interaction. Achiral oxoapomorphine, which was converted from chiral apomorphines
under aerobic conditions, served as the reactive species to form a covalent bond
at Cys77 of MDM2, leading to the inhibitory effect against the binding to p53.
PMID- 28400231
TI - Antiplasmodial beta-triketones from the flowers of the Australian tree Angophora
woodsiana.
AB - Chemical investigations of the MeOH extract of air dried flowers of the
Australian tree Angophora woodsiana (Myrtaceae) yielded two new beta-triketones,
woodsianones A and B (1, 2) and nine known beta-triketones (3-11). Woodsianone A
is a beta-triketone-sesquiterpene adduct and woodsianone B is a beta-triketone
epoxide derivative. The structures of the new and known compounds were elucidated
from the analysis of 1D/2D NMR and MS data. The relative configurations of the
compounds were determined from analysis of 1H-1H coupling constants and ROESY
correlations. All compounds (1-11) had antiplasmodial activity against the
chloroquine sensitive strain 3D7. The known compound rhodomyrtone (5) and new
compound woodsianone B (2) showed moderate antiplasmodial activities against the
3D7 strain (1.84uM and 3.00uM, respectively) and chloroquine resistant strain Dd2
(4.00uM and 2.53uM, respectively).
PMID- 28400232
TI - Practical application of 3-substituted-2,6-difluoropyridines in drug discovery:
Facile synthesis of novel protein kinase C theta inhibitors.
AB - We previously reported a facile preparation method of 3-substituted-2,6
difluoropyridines, which were easily converted to 2,3,6-trisubstituted pyridines
by nucleophilic aromatic substitution with good regioselectivity and yield. In
this study, we demonstrate the synthetic utility of 3-substituted-2,6
difluoropyridines in drug discovery via their application in the synthesis of
various 2,3,6-trisubstituted pyridines, including macrocyclic derivatives, as
novel protein kinase C theta inhibitors in a moderate to good yield. This
synthetic approach is useful for the preparation of 2,3,6-trisubstituted
pyridines, which are a popular scaffold for drug candidates and biologically
attractive compounds.
PMID- 28400233
TI - Identification of acylation products in SHAPE chemistry.
AB - SHAPE chemistry (selective 2'-hydroxyl acylation analyzed by primer extension)
has been developed to specifically target flexible nucleotides (often unpaired
nucleotides) independently to their purine or pyrimidine nature for RNA secondary
structure determination. However, to the best of our knowledge, the structure of
2'-O-acylation products has never been confirmed by NMR or X-ray data. We have
realized the acylation reactions between cNMP and NMIA under SHAPE chemistry
conditions and identified the acylation products using standard NMR spectroscopy
and LC-MS/MS experiments. For cAMP and cGMP, the major acylation product is the
2'-O-acylated compound (>99%). A trace amount of N-acylated cAMP has also been
identified by LC-UV-MS2. While for cCMP, the isolated acylation products are
composed of 96% of 2'-O-acylated, 4% of N,O-diacylated, and trace amount of N
acylated compounds. In addition, the characterization of the major 2'-O-acylated
compound by NMR showed slight differences in the conformation of the acylated
sugar between the three cyclic nucleotides. This interesting result should be
useful to explain some unexpected reactivity of the SHAPE chemistry.
PMID- 28400234
TI - Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as
microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo
efficacy in hyperalgesia pain model.
AB - A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4
d]imidazole derivatives have been synthesized and their mPGES-1 biological
activity has been disclosed in detail. Structure-activity relationship (SAR)
optimization provided inhibitors with excellent mPGES-1 potency and low to
moderate PGE2 release A549 cell potency. Among the mPGES-1 inhibitors studied, 7,
9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold
selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity.
Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic
stability in liver microsomes, high plasma protein binding (PPB) and no
significant inhibition observed in clinically relevant CYP isoforms. Besides,
selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic
profile and oral bioavailability (%F=33 and 85). Additionally, the representative
mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS
induced thermal hyperalgesia guinea pig pain model.
PMID- 28400235
TI - Rational design and synthesis of 2-anilinopyridinyl-benzothiazole Schiff bases as
antimitotic agents.
AB - Based on our previous results and literature precedence, a series of 2
anilinopyridinyl-benzothiazole Schiff bases were rationally designed by
performing molecular modeling experiments on some selected molecules. The binding
energies of the docked molecules were better than the E7010, and the Schiff base
with trimethoxy group on benzothiazole moiety, 4y was the best. This was followed
by the synthesis of a series of the designed molecules by a convenient synthetic
route and evaluation of their anticancer potential. Most of the compounds have
shown significant growth inhibition against the tested cell lines and the
compound 4y exhibited good antiproliferative activity with a GI50 value of 3.8uM
specifically against the cell line DU145. In agreement with the docking results,
4y exerted cytotoxicity by the disruption of the microtubule dynamics by
inhibiting tubulin polymerization via effective binding into colchicine domain,
comparable to E7010. Detailed binding modes of 4y with colchicine binding site of
tubulin were studied by molecular docking. Furthermore, 4y induced apoptosis as
evidenced by biological studies like mitochondrial membrane potential, caspase-3,
and Annexin V-FITC assays.
PMID- 28400237
TI - Cytochrome P450 binding studies of novel tacrine derivatives: Predicting the risk
of hepatotoxicity.
AB - The 1,2,3,4-tetrahydroacridine derivative tacrine was the first drug approved to
treat Alzheimer's disease (AD). It is known to act as a potent cholinesterase
inhibitor. However, tacrine was removed from the market due to its hepatotoxicity
concerns as it undergoes metabolism to toxic quinonemethide species through the
cytochrome P450 enzyme CYP1A2. Despite these challenges, tacrine serves as a
useful template in the development of novel multi-targeting anti-AD agents. In
this regard, we sought to evaluate the risk of hepatotoxicity in a series of C9
substituted tacrine derivatives that exhibit cholinesterase inhibition
properties. The hepatotoxic potential of tacrine derivatives was evaluated using
recombinant cytochrome (CYP) P450 CYP1A2 and CYP3A4 enzymes. Molecular docking
studies were conducted to predict their binding modes and potential risk of
forming hepatotoxic metabolites. Tacrine derivatives compound 1 (N-(3,4
dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine) and 2 (6-chloro-N-(3,4
dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine) which possess a C9 3,4
dimethoxybenzylamino substituent exhibited weak binding to CYP1A2 enzyme (1,
IC50=33.0uM; 2, IC50=8.5uM) compared to tacrine (CYP1A2 IC50=1.5uM). Modeling
studies show that the presence of a bulky 3,4-dimethoxybenzylamino C9 substituent
prevents the orientation of the 1,2,3,4-tetrahydroacridine ring close to the heme
iron center of CYP1A2 thereby reducing the risk of forming hepatotoxic species.
PMID- 28400236
TI - Synthesis, antiplatelet and antithrombotic activities of resveratrol derivatives
with NO-donor properties.
AB - Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular
system; however, drawbacks including low bioavailability and fast metabolism
limit its efficacy. In this work we described new resveratrol derivatives with
nitric oxide (NO) release properties, ability to inhibit platelet aggregation and
in vivo antithrombotic effect. Compounds (4a-f) were able to release NO in vitro,
at levels ranging from 24.1% to 27.4%. All compounds (2a-f and 4a-f) have
exhibited platelet aggregation inhibition using as agonists ADP, collagen and
arachidonic acid. The most active compound (4f) showed reduced bleeding time
compared to acetylsalicylic acid (ASA) and protected up to 80% against in vivo
thromboembolic events. These findings suggest that hybrid resveratrol-furoxan
(4f) is a novel lead compound able to prevent platelet aggregation and
thromboembolic events.
PMID- 28400238
TI - Novel bioactive molecules from Lentzea violacea strain AS 08 using one strain
many compounds (OSMAC) approach.
AB - A new eudesmane sesquiterpenoid (1), and a new homologue of virginiae butanolide
E (2) along with butyl isobutyl phthalate (3) were isolated from, actinomycete
Lentzea violacea strain AS08 isolated from north western Himalayas by stressing
on modified one strain-many compounds (OSMAC) method. The structures of the new
compounds were elucidated by extensive spectroscopic analyses including 1D, 2D
NMR along with HR-ESI-MS and FT-IR data. Herein, a distinctive method was added
for inspecting secretory profile of the strain by quantification of extract value
of cell free supernatant in different types of culture media fallowed by HPLC
profiling of respective extracts, which revealed a highly altered metabolic
profile of the strain and formed the base for the selection of media. The
compounds 1 and 2 showed moderate activity against Gram negative (MIC ~32-64ugml
1) in comparison to Gram positive bacterial pathogens. Compound 1 exhibited
significant activity in human cancerous cell lines (IC50 ~19.2uM).
PMID- 28400239
TI - Efficient synthesis of a multi-substituted diphenylmethane skeleton as a steroid
mimetic.
AB - Steroids are important components of cell membranes and are involved in several
physiological functions. A diphenylmethane (DPM) skeleton has recently been
suggested to act as a mimetic of the steroid skeleton. However, difficulties are
associated with efficiently introducing different substituents between two phenyl
rings of the DPM skeleton, and, thus, further structural development based on the
DPM skeleton has been limited. We herein developed an efficient synthetic method
for introducing different substituents into two phenyl rings of the DPM skeleton.
We also synthesized DPM-based estrogen receptor (ER) modulators using our
synthetic method and evaluated their ER transcriptional activities.
PMID- 28400240
TI - Skin lesion from Maldives: Classic but forgotten.
PMID- 28400241
TI - Highlights from the 30th North American Cystic Fibrosis Conference, Orlando 2016.
AB - This is a selection of papers presented at the 30th North American Cystic
Fibrosis Conference held in Orlando in October 2016. The papers discussed are
thought to be of particular interest to CF caregivers in the UK. We highlight the
major themes covered in the conference including novel therapies, recently
published and proposed guidelines and insights from registry studies.
PMID- 28400242
TI - The impact of co-morbidity in childhood cystic fibrosis.
AB - A number of risk factors have been identified for deterioration of lung disease
in children with Cystic Fibrosis (CF), and current management strategies are
based on the prevention and treatment of such elements. Further challenge ensues
when a patient has co-morbid disease in addition to CF, particularly when faced
with rapidly deteriorating pulmonary status. It is difficult to measure the
contribution of other pathologies to this decline and optimisation of both CF
care and co-morbidity is paramount. This review explores the challenges faced
when treating children with CF and co-morbid conditions, focussing on
gastroesophageal reflux disease pre- and post-lung transplantation.
PMID- 28400244
TI - The interconnection of mental fatigue and aging: An EEG study.
AB - Mental fatigue, a state of reduced alertness and decreased overall performance
due to prolonged cognitive activity, is a major cause for a large number of
accidents in traffic and industry. Against the background of an aging workforce,
the investigation of the interconnection of mental fatigue and aging is of great
practical relevance. In the present study, a group of younger and a group of
older adults performed a cognitive task for 3h. The experimental design also
comprised breaks with various durations. Beside behavioral data, the spectral
properties of the ongoing EEG with respect to time on task and breaks were
analyzed. No differences between the age groups were found in behavior, but
electrophysiological measures provide some evidence that older adults in our
study were differentially affected by time on task. In the later course of the
experiment modulations in frontal theta power became larger for older, compared
to younger adults. This may indicate strain due to task demands, eventually
resulting from the deployment of compensatory processes. Occipital alpha, which
has been linked to internally oriented brain states, saturates faster in younger
adults. It thus maybe, that especially the younger participants' performance
deteriorated due to the monotonous nature of the task itself. Both mechanisms, an
increased consumption of cognitive resources in older adults and a decrease of
motivation in younger adults, could mask differences in performance decrements
between the age groups due to mental fatigue.
PMID- 28400245
TI - Psychophysiological correlates of the misinformation effect.
AB - The misinformation effect refers to memory impairment that arises after exposure
to misleading information (Loftus, 2005, p. 361). The present study focuses on
the peripheral psychophysiology of false memories induced in a misleading
information paradigm. On the basis of Sokolov's orienting reflex and studies
concerning the Concealed Information Test (CIT, Lykken, 1959), the main
hypothesis assumes differences between true and false memories in terms of the
accompanying autonomic measures. It also is assumed that a cued recall of
original information preceding the recollection phase reduces misinformation
effects. Seventy-five participants watched a video that included nine randomized
details. After a ten-minute retention phase, the subjects read a narrative text.
Six out of the nine details were replaced by misleading details. Following this,
the participants completed a cued recall task for three of the original items. In
a subsequent CIT with truthful answering electrodermal responses, phasic heart
rate, respiration, and response behavior were measured. Finally, the level of
confidence and source monitoring were assessed. The misinformation effect was
replicated with newly developed materials in three recollection tasks. Cued
recall had no influence on the misinformation effect. Autonomic measures did not
differ between true and false memories in the CIT. Electrodermal responses
reflected the subjective importance the participants attributed to details in the
source monitoring task. Therefore, electrodermal responses are interpreted as a
correlate of subjective remembering in a misinformation paradigm.
PMID- 28400243
TI - Cancer Manipulation of Host Physiology: Lessons from Pancreatic Cancer.
AB - Homeostasis is a fundamental property of living organisms enabling the human body
to withstand internal and external insults. In several chronic diseases, and
especially in cancer, many homeostatic mechanisms are deranged. Pancreatic cancer
in particular is notorious for its ability to invoke an intense fibroinflammatory
stromal reaction facilitating its progression and resistance to treatment. In the
past decade, several seminal discoveries have elucidated previously unrecognized
modes of commandeering the host's defense systems. Here we review novel
discoveries in pancreatic cancer immunobiology and attempt to integrate the
notion of deranged homeostasis in the pathogenesis of this disease. We also
highlight areas of controversy and obstacles that need to be overcome, hoping to
further our mechanistic insight into this malignancy.
PMID- 28400246
TI - The effects of captivity survival training on mood, dissociation, PTSD symptoms,
cognitive performance and stress hormones.
AB - In the Canadian Armed Forces (CAF), Conduct After Capture (CAC) training is a 4
day captivity survival course during which soldiers are exposed to increasing
stress, and evaluated on their ability to accomplish military objectives. We
hypothesized that: (a) compared to baseline, CAC training would cause
significant, reversible perturbations in measures of psychological functioning
and serum and salivary stress hormone levels relevant to models of stress
hardiness and vulnerability; and (b) deviations from baseline would be maximal at
the time point of most intense stress during training. CAF personnel were
assessed at baseline, twice during training (immediately prior to a less
challenging interrogation role-play scenario and again following another much
more intense interrogation role-play scenario), and after completion of training.
At each occasion, mood, fatigue, dissociation, PTSD symptoms, short-term and
working memory, and salivary cortisol and dehydroepiandrosterone (DHEA) were
assessed. As predicted, scores on all measures were degraded during CAC but
recovered after completion of training, and almost all measures were most
degraded at the more intense interrogation role-play scenario. Unexpectedly,
memory performance was unaffected by training, suggesting that a short duration
of intense stress might be insufficient for degrading it. Another unexpected
finding was that mood assessed prior to training predicted successful completion
of training, which bears important practical implications for increasing the
success rate of training in similar environments. These results demonstrate that
despite its relative brevity, CAC training nevertheless induces significant but
reversible effects on psychological and physiological function-necessary
preconditions for stress inoculation training.
PMID- 28400248
TI - A Predictive Diagnosis: Organizing Pneumonia.
PMID- 28400247
TI - Quality of Life, Dyspnea, and Functional Exercise Capacity Following a First
Episode of Pulmonary Embolism: Results of the ELOPE Cohort Study.
AB - BACKGROUND: We aimed to evaluate health-related quality of life (QOL), dyspnea,
and functional exercise capacity during the year following the diagnosis of a
first episode of pulmonary embolism. METHODS: This was a prospective multicenter
cohort study of 100 patients with acute pulmonary embolism recruited at 5
Canadian hospitals from 2010-2013. We measured the outcomes QOL (by Short-Form
Health Survey-36 [SF-36] and Pulmonary Embolism Quality of Life [PEmb-QoL]
measures), dyspnea (by the University of California San Diego Shortness of Breath
Questionnaire [SOBQ]) and 6-minute walk distance at baseline and 1, 3, 6, and 12
months after acute pulmonary embolism. Computed tomography pulmonary angiography
was performed at baseline, echocardiogram was performed within 10 days, and
cardiopulmonary exercise testing was performed at 1 and 12 months. Predictors of
change in QOL, dyspnea, and 6-minute walk distance were assessed by repeated
measures mixed-effects models analysis. RESULTS: Mean age was 50.0 years; 57%
were male and 80% were treated as outpatients. Mean scores for all outcomes
improved during 1-year follow-up: from baseline to 12 months, mean SF-36 physical
component score improved by 8.8 points, SF-36 mental component score by 5.3
points, PEmb-QoL by -32.1 points, and SOBQ by -16.3 points, and 6-minute walk
distance improved by 40 m. Independent predictors of reduced improvement over
time were female sex, higher body mass index, and percent-predicted VO2 peak <80%
on 1 month cardiopulmonary exercise test for all outcomes; prior lung disease and
higher pulmonary artery systolic pressure on 10-day echocardiogram for the
outcomes SF-36 physical component score and dyspnea score; and higher main
pulmonary artery diameter on baseline computed tomography pulmonary angiography
for the outcome PEmb-QoL score. CONCLUSIONS: On average, QOL, dyspnea, and
walking distance improve during the year after pulmonary embolism. However, a
number of clinical and physiological predictors of reduced improvement over time
were identified, most notably female sex, higher body mass index, and exercise
limitation on 1-month cardiopulmonary exercise test. Our results provide new
information on patient-relevant prognosis after pulmonary embolism.
PMID- 28400249
TI - Similarity of osmoregulatory capacity in coastal and inland alligator gar.
AB - The alligator gar Atractosteus spatula is a primitive fish species, occupying a
wide range of temperature and salinity habitats. Long-distance movements are
limited, leading to genetic differentiation between inland and coastal
populations. Unknown is whether physiological capacity differs between
geographically separated populations, particularly for traits important to
osmoregulation in saline environments. Alligator gar from inland and coastal
populations were reared in a similar environment and exposed to temperature (10,
30 degrees C) and salinity (0, 20ppt) extremes to determine whether iono- and
osmoregulatory ability differed between populations. There were few differences
in osmoregulatory ability between populations, with similar gill, blood and
gastrointestinal tract osmoregulatory parameters. Blood plasma osmolality, ion
concentrations, intestinal pH and bicarbonate base concentrations, intestinal
fluid osmolality, ion concentrations and gill Na+, K+-ATPase (NKA) activity were
similar between populations. Notably, gar from both populations did not
osmoregulate well at low temperature and high salinity, with elevated plasma
osmolality and ion concentrations, low gill NKA, and little evidence of
gastrointestinal tract contribution to ionic and base regulation based on a lack
of intestinal fluid and low base content. Therefore, the hypothesis that coastal
gar would have improved osmotic regulatory ability in saline environments as
compared to inland alligator gar was not supported, suggesting physiological
capacity may be retained in primitive species possibly due to its importance to
their persistence through time.
PMID- 28400250
TI - Assessment of self-care and medication adherence in individuals with mental
health conditions.
AB - OBJECTIVES: This descriptive study explored whether patients with mental health
conditions engage in personal medicine (self-care activities) as part of their
treatment regimen. Personal medicine is patient-identified and -initiated
activities of self-care that can improve mental health through various means,
including physical activity, social engagement, and spiritual connectedness. The
purpose of this study was to explore patient engagement in personal medicine
within an underserved population and to evaluate the impact self-care might have
on self-reported medication use and adherence and patient perception of mental
health control. DESIGN: Cross-sectional study design with a face-to-face verbally
administered survey assessing medication adherence, engagement in self-care
activities, perception of self-care, and mental health control. SETTING: The
study site was a nonprofit charitable pharmacy in an urban setting. The pharmacy
provides medications and pharmacy services at no charge, including disease state
education, point-of-care testing, and medication therapy management.
PARTICIPANTS: Study participants included those who fill medications for mental
health conditions and who are age 18 years and older. MAIN OUTCOME MEASURES: Main
outcomes included engagement in self-care and self-reported medication adherence.
Additional measures included stratification of dimensions of self-care,
perception of mental health control, and patient knowledge of community
resources. RESULTS: Overall, 81.7% of participants engaged in activities of self
care, with 98.3% recognizing self-care as important to improving and maintaining
their mental health. Greater self-reported adherence rates and mental health
control were seen with patients who participate in self-care. CONCLUSION:
Participants who identify and engage in personal medicine recognize its value and
are willing to incorporate it into their treatment regimen. As accessible and
trusted health care providers, pharmacists can encourage patients to identify and
use personal medicine to aid in the improvement of their mental health condition.
PMID- 28400251
TI - A survey of pharmacists' preparedness for provider status implementation.
AB - OBJECTIVES: 1) To measure pharmacists' preparedness for the implementation of
provider status; and 2) to measure pharmacists' perceived stakeholder readiness
for provider status implementation. METHODS: An anonymous 24-item electronic
survey was sent to a convenience sample of approximately 1500 licensed Iowa
pharmacists. They were contacted by means of their membership in the Iowa
Pharmacists Association, 1 of 6 regional associations; Drake University and
University of Iowa faculty listservs; and the University of Iowa alumni office.
Pharmacists received initial contact through e-mail, private groups on social
media, or respective organizations' websites requesting participation.
Respondents' confidence to provide clinical skills and perceived preparedness for
provider status implementation were measured. RESULTS: One hundred thirty-two
pharmacists completed the survey. Participants perceived high confidence in
themselves to serve as providers and low confidence in the preparedness of payers
to support pharmacist provider status. Participants reported feeling most
confident in obtaining a medication history and past medical history and least
confident in obtaining vital signs and providing point-of-care testing.
CONCLUSION: If provider status for pharmacists becomes law, Iowa pharmacists
should expand on initiatives in collaboration with stakeholders to make a
smoother transition into provider status. Iowa pharmacists may benefit from
educational programming focused on delivering components of clinical services,
such as measuring vital signs and point-of-care testing. Future research can be
conducted to explain pharmacists' confidence levels as well as intentions to
implement provider status services.
PMID- 28400252
TI - You never know when you'll need a Vicodin: An era of opioid abuse.
PMID- 28400253
TI - Perceived sustainability of community telepharmacy in North Dakota.
AB - OBJECTIVES: To assess the sustainability of the business model underlying the
North Dakota Telepharmacy Project (NDTP). SETTING: Of the 38 community pharmacy
organizations (14 central, 24 remote), 27 organizations (11 central and 16 remote
sites) in North Dakota provided a useable set of responses (71.1% response rate).
A twelfth organization (a community pharmacy) ceased operations over the study's
time frame and was not included in the data analysis. PRACTICE DESCRIPTION:
Emphasis is placed on NDTP community telepharmacies, because the community
telepharmacy business model is more established than hospital telepharmacies. Yet
little is known about the long-run financial viability of telepharmacies.
PRACTICE INNOVATION: Originally funded by a series of federal grants, the goal of
the NDTP was to create the infrastructure necessary to support the development of
telepharmacy sites. A 48-item questionnaire assessed the self-reported
operational, financial, and community impacts of a community telepharmacy.
EVALUATION: The questionnaire was administered from December 2015 to February
2016 to all NDTP community telepharmacy owners-managers. Thus, 1 participant
(owner-manager) addressed both central and remote-site locations served by a
pharmacy. RESULTS: Most respondents reported that their telepharmacy sites
(especially remote sites) generate small positive financial returns for the
organization. Respondents also reported that the closure of their remote sites
would significantly harm the communities they serve. CONCLUSION: NDTP aims of
restoration and retention have been achieved via the investment and shared
decision making with pharmacy owners in North Dakota. The telepharmacy model is
sustainable, even if it does not generate significant economic profit.
PMID- 28400254
TI - Community pharmacist-delivered Medicare Annual Wellness Visits within a family
medicine practice.
AB - OBJECTIVE: To identify the steps to implement a community pharmacist into a
family medicine practice to deliver Medicare Annual Wellness Visits (AWVs).
SETTING: Medicine Mart Pharmacy is a locally owned and operated pharmacy that has
served the West Columbia, SC, area for over 30 years. The services offered by the
pharmacy have expanded over the past 3 years through the addition of a community
pharmacy resident. PRACTICE INNOVATION: A stepwise approach was developed for a
community pharmacist to identify, market, and establish an AWV service through a
collaborative practice agreement with a local family medicine practice.
EVALUATION: The pharmacy team contacted each office and obtained information
about the physician practices and their willingness to participate in the
program. Two financial models were created and evaluated to determine budget
implications. RESULTS: Many patients were seen at the physician offices; they
were eligible for AWV, but had not received them. Meetings were scheduled with 3
of the 6 offices; however, none of the offices moved forward with the proposed
program. CONCLUSION: Integrating a pharmacist into the AWV role may be profitable
to both the pharmacy and the medical office with persistence and time to have a
successful collaboration.
PMID- 28400255
TI - Association of authorized generic marketing with prescription drug spending on
antidepressants from 2000 to 2011.
AB - OBJECTIVES: Prior research suggests that authorized generic drugs increase
competition and decrease prices, but little empirical evidence supports this
conclusion. This study evaluated the impact of authorized generic marketing on
brand and generic prices. DESIGN: Longitudinal analysis of the household
component of the Medical Expenditure Panel Survey. SETTING: Interview panels over
12 years, with a new panel each year. For each panel, 5 rounds of household
interviews were conducted over 30 months. PATIENTS OR PARTICIPANTS: Nationally
representative sample of the U.S. civilian noninstitutionalized population,
focusing on people using 1 of 5 antidepressant drugs that became generically
available between 2000 to 2011. INTERVENTION: Drugs and dose/formulations with
versus without an authorized generic drug marketed. MAIN OUTCOME MEASURES:
Multiple linear regression models with lagged variables evaluated the effect of
an authorized generic on average inflation-adjusted brand and generic price,
adjusting for payment sources, generic entry time, competitor price, and year.
RESULTS: During 2000-2011, annual brand antidepressant utilization decreased from
51.47 to 7.52 million prescriptions, and generic antidepressant utilization
increased from 0 to 88.83 million prescriptions. Over time, payment per
prescription for brand prescriptions increased 25% overall, and generic payments
decreased 70% for all payer types. With unadjusted data, after generic entry the
average brand price decreased $0.59 per year with and $3.62 per year without an
authorized generic in the market. Average generic prices decreased $10.30 per
year with and $8.47 per year without an authorized generic in the market. In
multiple regression models with lagged variables adjusted for heteroscedasticity,
payer source, time since generic entry, competitor price, and year, authorized
generics significantly reduced average payment for generic (-$3.03) and brand (
$60.64) prescriptions, and over time this price change slowly diminished.
CONCLUSION: Availability of an authorized generic was associated with reduced
average generic and brand price in the antidepressant market, supporting prior
evidences.
PMID- 28400256
TI - N-oleoyldopamine modulates activity of midbrain dopaminergic neurons through
multiple mechanisms.
AB - N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in
catecholaminergic neurons. The present study investigates OLDA targets in
midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons
recorded in brain slices were excited by OLDA in wild type mice. In transient
receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA
neurons displayed sustained inhibition of firing. In the presence of the dopamine
type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker
nomifensine no such inhibition was observed. Under sulpiride OLDA slightly
excited SNc DA neurons, an action abolished upon combined application of the
cannabinoid1 and 2 receptor antagonists AM251 and AM630. In ventral tegmental
area (VTA) DA neurons from TRPV1 KO mice a transient inhibition of firing by OLDA
was observed. Thus OLDA modulates the firing of nigrostriatal DA neurons through
interactions with TRPV1, cannabinoid receptors and dopamine uptake. These
findings suggest further development of OLDA-like tandem molecules for the
treatment of movement disorders including Parkinson's disease.
PMID- 28400257
TI - Phase-amplitude coupled persistent theta and gamma oscillations in rat primary
motor cortex in vitro.
AB - In vivo, theta (4-7 Hz) and gamma (30-80 Hz) neuronal network oscillations are
known to coexist and display phase-amplitude coupling (PAC). However, in vitro,
these oscillations have for many years been studied in isolation. Using an
improved brain slice preparation technique we have, using co-application of
carbachol (10 MUM) and kainic acid (150 nM), elicited simultaneous theta (6.6 +/-
0.1 Hz) and gamma (36.6 +/- 0.4 Hz) oscillations in rodent primary motor cortex
(M1). Each oscillation showed greatest power in layer V. Using a variety of time
series analyses we detected significant cross-frequency coupling in 74% of slice
preparations. Differences were observed in the pharmacological profile of each
oscillation. Thus, gamma oscillations were reduced by the GABAA receptor
antagonists, gabazine (250 nM and 2 MUM), and picrotoxin (50 MUM) and augmented
by AMPA receptor antagonism with SYM2206 (20 MUM). In contrast, theta oscillatory
power was increased by gabazine, picrotoxin and SYM2206. GABAB receptor blockade
with CGP55845 (5 MUM) increased both theta and gamma power, and similar effects
were seen with diazepam, zolpidem, MK801 and a series of metabotropic glutamate
receptor antagonists. Oscillatory activity at both frequencies was reduced by the
gap junction blocker carbenoxolone (200 MUM) and by atropine (5 MUM). These data
show theta and gamma oscillations in layer V of rat M1 in vitro are cross
frequency coupled, and are mechanistically distinct. The development of an in
vitro model of phase-amplitude coupled oscillations will facilitate further
mechanistic investigation of the generation and modulation of coupled activity in
mammalian cortex.
PMID- 28400258
TI - Gating modifier toxin interactions with ion channels and lipid bilayers: Is the
trimolecular complex real?
AB - Spider peptide toxins have attracted attention because of their ability to target
voltage-gated ion channels, which are involved in several pathologies including
chronic pain and some cardiovascular conditions. A class of these peptides acts
by modulating the gating mechanism of voltage-gated ion channels and are thus
called gating modifier toxins (GMTs). In addition to their interactions with
voltage-gated ion channels, some GMTs have affinity for lipid bilayers. This
review discusses the potential importance of the cell membrane on the mode of
action of GMTs. We propose that peptide-membrane interactions can anchor GMTs at
the cell surface, thereby increasing GMT concentration in the vicinity of the
channel binding site. We also propose that modulating peptide-membrane
interactions might be useful for increasing the therapeutic potential of spider
toxins. Furthermore, we explore the advantages and limitations of the
methodologies currently used to examine peptide-membrane interactions. Although
GMT-lipid membrane binding does not appear to be a requirement for the activity
of all GMTs, it is an important feature, and future studies with GMTs should
consider the trimolecular peptide-lipid membrane-channel complex. This article is
part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological
Tools.'
PMID- 28400259
TI - A role for the peripheral immune system in the development of alcohol use
disorders?
AB - Preclinical studies have largely supported that alcohol-consumption induces the
development of an important neuro-inflammation and this neuro-inflammation
contributes to alcohol-drinking behaviors, notably through TLR4 and LPS related
mechanisms. The neuro-inflammation originates from a direct interaction of
ethanol with the neuronal and immune brain cells, but also from the generation of
an inflammation at the periphery. Ethanol in particular interacts with the
intestine to develop a gut dysbiosis and an increase in gut permeability, that
allows the liberation of bacterial fragments to the systemic circulation and
induces a pro-inflammatory response in the systemic circulation and peripheral
organs, and in particular the liver. Peripheral cytokines or activated peripheral
cells may cross the blood-brain barrier and activate neuro-inflammation. In
humans, peripheral inflammation and intestinal dysbiosis are related to symptoms
of alcohol use disorders (AUD), such as depression, anxiety and alcohol-craving,
However, the dysbiosis, could also participate in a different manner to the
symptomatology of the addiction, possibly by interacting with the stress system,
by interfering with the sleep processes and altering the abilities for social
interactions. The role of the gut suggests that interventions with probiotics or
prebiotics might in the future be of interest for the treatment of the addiction.
This article is part of the Special Issue entitled "Alcoholism".
PMID- 28400260
TI - Prevention of the adverse effects of olanzapine on lipid metabolism with the
antiepileptic zonisamide.
AB - BACKGROUND: Atypical antipsychotic drugs, particularly olanzapine, represent a
mainstay in the treatment of psychoses; however, their use is commonly associated
with weight gain and diabetes. The aim of this study was to determine whether
combined administration of olanzapine and zonisamide can be used to prevent
olanzapine-induced metabolic disturbances. METHODS AND RESULTS: These experiments
involved female Sprague Dawley rats (n = 6-8/group) that were administered
olanzapine, either acutely (6 mg/kg, s. c) or via continuous osmotic minipump
infusion (6 mg/kg/day for 6 or 14 days), in combination with zonisamide (26
mg/kg/day,i.p.). Continuous infusion of olanzapine induced accumulation of
adipose tissue and an associated reduction in stimulated lipolysis and reduced
protein expression of CGI-58, a critical co-activator of ATGL. Olanzapine
treatment caused a preferential shift toward carbohydrate oxidation (or reduced
fat oxidation), elevated blood triglycerides and a reduction in locomotor
activity. Olanzapine had a direct effect on glucose regulation, causing rapid
hyperglycemia, and a reduction in glucose tolerance and insulin sensitivity.
Continuous administration of olanzapine caused significant hyperinsulinemia and a
significant reduction in insulin sensitivity. Zonisamide did not affect the
impact of olanzapine on glucose homeostasis. On the other hand, co-administration
of olanzapine with zonisamide completely ameliorated olanzapine-mediated shifts
in lipid metabolism resulting in a normalization of olanzapine-induced weight
gain. CONCLUSION: These data collectively show an impact of olanzapine on body
weight and lipid metabolism, which is ameliorated by co-administration with
zonisamide. These findings suggest that a combined olanzapine and zonisamide
approach might reduce weight gain, but will not provide protection against
olanzapine-induced glucose intolerance.
PMID- 28400261
TI - Involvement of astrocytic CYP1A1 isoform in the metabolism and toxicity of the
alkaloid pyrrolizidine monocrotaline.
AB - Monocrotaline (MCT) and its pyrrole derivative, dehydromonocrotaline (DHMC),
interact with molecular targets in cells of the central nervous system. DHMC
presents higher toxicity than MCT indicating that its metabolism of MCT is a
critical step of this alkaloid toxicity. This study sought to elucidate the
metabolism and the toxicity of MCT in C6 astrocyte cell line and primary cultures
of rat astrocytes by investigating metabolic enzymatic mechanisms of the
cytochrome P450 (CYP) system and conjugation with glutathione. Treatment with
omeprazole (OMP) (20 MUM), a non-specific inducer of CYP450 induced approximately
10-fold increase in CYP1A1 activity after 2 h of treatment. Similarly, the 7
Ethoxyresorufin-O-deethylase (EROD) activity was induced by treatment with MCT
(100-500 MUM), indicating that the P450 CYP1A1 isoform was active and involved in
the metabolism of MCT. Analysis of conjugation with glutathione showed a
significant depletion of GSH after MCT (500 MUM) treatment, and this was
partially reversed by pretreatment with a P450 inhibitor (cimetidine 100 MUM).
These results suggest that not only the alkaloid MCT but, also its metabolite may
deplete GSH. Rosenfeld staining showed intense vacuolization after MCT treatment,
which was partially inhibited in the presence of a P450 activator. MTT test
showed that association of MCT with OMP induced a reduction in cell viability in
C6 and primary astrocytic cells. These results demonstrate that MCT is
metabolized by astrocytic CYP1A1 to generate metabolites that can deplete GSH.
Moreover, changes in the activity of the P450 enzymes interfere with the
cytotoxic effects induced by the alkaloid.
PMID- 28400262
TI - Identification of short single disulfide-containing contryphans from the venom of
cone snails using de novo mass spectrometry-based sequencing methods.
AB - We identified 12 short single disulfide-containing conopeptides from the venom of
Conus coronatus, C. leopardus, C. lividus and C. zonatus. Interestingly, we
detected the shortest contryphan sequence thus far characterized which contains
only six amino acid residues. We also identified three distinct contryphan
sequences of C. lividus without any proline residues and one sequence with an
unusual post-translational modification (bromination of tryptophan). Furthermore,
we characterized venom peptides of C. zonatus for the first time.
PMID- 28400263
TI - Peptidomimetic hydroxamate metalloproteinase inhibitors abrogate local and
systemic toxicity induced by Echis ocellatus (saw-scaled) snake venom.
AB - The ability of two peptidomimetic hydroxamate metalloproteinase inhibitors,
Batimastat and Marimastat, to abrogate toxic and proteinase activities of the
venom of Echis ocellatus from Cameroon and Ghana was assessed. Since this venom
largely relies for its toxicity on the action of zinc-dependent
metalloproteinases (SVMPs), the hypothesis was raised that toxicity could be
largely eliminated by using SVMP inhibitors. Both hydroxamate molecules inhibited
local and pulmonary hemorrhagic, in vitro coagulant, defibrinogenating, and
proteinase activities of the venoms in conditions in which venom and inhibitors
were incubated prior to the test. In addition, the inhibitors prolonged the time
of death of mice receiving 4 LD50s of venom by the intravenous route. Lower
values of IC50 were observed for in vitro and local hemorrhagic activities than
for systemic effects. When experiments were performed in conditions that
simulated the actual circumstances of snakebite, i.e. by administering the
inhibitor after envenoming, Batimastat completely abrogated local hemorrhage if
injected immediately after venom. Moreover, it was also effective at inhibiting
lethality and defibrinogenation when venom and inhibitor were injected by the
intraperitoneal route. Results suggest that these, and possibly other,
metalloproteinase inhibitors may become an effective adjunct therapy in
envenomings by E. ocellatus when administered at the anatomic site of venom
injection rapidly after the bite.
PMID- 28400265
TI - Convergence of semantics and emotional expression within the IFG pars orbitalis.
AB - Humans communicate through a combination of linguistic and emotional channels,
including propositional speech, writing, sign language, music, but also prosodic,
facial, and gestural expression. These channels can be interpreted separately or
they can be integrated to multimodally convey complex meanings. Neural models of
the perception of semantics and emotion include nodes for both functions in the
inferior frontal gyrus pars orbitalis (IFGorb). However, it is not known whether
this convergence involves a common functional zone or instead specialized
subregions that process semantics and emotion separately. To address this, we
performed Kernel Density Estimation meta-analyses of published neuroimaging
studies of the perception of semantics or emotion that reported activation in the
IFGorb. The results demonstrated that the IFGorb contains two zones with distinct
functional profiles. A lateral zone, situated immediately ventral to Broca's
area, was implicated in both semantics and emotion. Another zone, deep within the
ventral frontal operculum, was engaged almost exclusively by studies of emotion.
Follow-up analysis using Meta-Analytic Connectivity Modeling demonstrated that
both zones were frequently co-activated with a common network of sensory, motor,
and limbic structures, although the lateral zone had a greater association with
prefrontal cortical areas involved in executive function. The status of the
lateral IFGorb as a point of convergence between the networks for processing
semantic and emotional content across modalities of communication is intriguing
since this structure is preserved across primates with limited semantic
abilities. Hence, the IFGorb may have initially evolved to support the
comprehension of emotional signals, being later co-opted to support semantic
communication in humans by forming new connections with brain regions that formed
the human semantic network.
PMID- 28400264
TI - The influence of low-level stimulus features on the representation of contexts,
items, and their mnemonic associations.
AB - Since the earliest attempts to characterize the "receptive fields" of neurons, a
central aim of many neuroscience experiments is to elucidate the information that
is represented in various regions of the brain. Recent studies suggest that, in
the service of memory, information is represented in the medial temporal lobe in
a conjunctive or associative form with the contextual aspects of the experience
being the primary factor or highest level of the conjunctive hierarchy. A
critical question is whether the information that has been observed in these
studies reflects notions such as a cognitive representation of context or whether
the information reflects the low-level sensory differences between stimuli. We
performed two functional magnetic resonance imaging experiments to address this
question and we found that associative representations observed between context
and item (and order) in the human brain can be highly influenced by low-level
sensory differences between stimuli. Our results place clear constraints on the
experimental design of studies that aim to investigate the representation of
contexts and items during performance of associative memory tasks. Moreover, our
results raise interesting theoretical questions regarding the disambiguation of
memory-related representations from processing-related representations.
PMID- 28400267
TI - CHD5 is a potential tumor suppressor in non small cell lung cancer (NSCLC).
AB - Lung cancer is one of the deadliest types of cancers and genetic and epigenetic
alterations play major roles in its development. Chromodomain (CHD) protein
family acts in chromatin organization, regulation of transcription and also
genomic stability and cancer prevention. Although CHD5, a member of this family
was shown to contribute to major cellular events and functions as a tumor
suppressor gene in various types of cancer, it is not clear whether CHD5 plays a
role in lung carcinogenesis. The aim of this study was to investigate the
possible role of CHD5 in progression of non-small cell lung cancer (NSCLC).
Expression levels of CHD5 gene in 59 tumor and corresponding non-cancerous lung
tissue samples were analyzed by qRT-PCR and the methylation status of the
promoter region was investigated by methylation specific PCR (MS-PCR). The Akt
phosphorylation levels were investigated by Western Blot (WB). CHD5 was down
regulated in 17 (39.5%) and up-regulated in 24 (55.8%) of tumor specimens. Even
though the promoter of CHD5 was hypermethylated in 8 patients, it was not found
associated with CHD5 gene expression (p=0.08). Akt phosphorylation was increased
in 14 (53.8%) and decreased in 12 (46.2%) of the samples but no significant
association was found between p-Akt phosphorylation and CHD5 expression (p=0.67).
We suggest that CHD5 may act as a tumor suppressor gene in NSCLC.
PMID- 28400268
TI - Genetic evidence supporting the taxonomic separation of the Arabian and Northwest
African subspecies of the desert hedgehog (Paraechinus aethiopicus).
AB - Traditional subspecies call attention to differences between geographic
populations with research potential, but their value is often in need of
revision. Genetic data can be useful for evaluating the taxonomic validity of
historical species and subspecies designations or for identifying morphologically
cryptic divergent lineages worthy of further in-depth taxonomic study. The desert
hedgehog (Paraechinus aethiopicus) has a wide but fragmented distribution in arid
and semi-arid habitats from the northwest to the northeast of Africa and
southwestern Asia, and its taxonomy is still unclear. We used mitochondrial
(cytochrome b, Cyt b, and 12S ribosomal RNA, 12S) and nuclear (breast cancer type
1 susceptibility protein, BRCA1, and apolipoprotein B, Apob) DNA sequence data to
assess the degree of genetic divergence between two of its three major proposed
subspecies: Arabian (P. a. dorsalis) and Northwest African (P. a. deserti); this
is the first molecular evaluation of the taxonomy of P. aethiopicus. Phylogenetic
analyses, comparison of interspecific and intraspecific genetic distances
observed across hedgehog species, and molecular species delimitation methods
(distance-based clustering and tree-based), all indicate a level of genetic
differentiation between dorsalis and deserti that is compatible with their
taxonomic separation. Their divergence in the studied genes were consistently
comparable to, or greater than, several intrageneric and a few intergeneric
distances in hedgehogs. The Cyt b net Kimura 2-parameter distance between
dorsalis and deserti was 10.8+/-1.3%, which is about the mean between congeneric
species in reviews of Cyt b distances for mammals. This study, as a test of the
genetic distinctiveness of dorsalis and deserti, suggests that they represent
evolutionarily significant units and flags them for future phylogeographic and
taxonomic investigations.
PMID- 28400266
TI - EEG Mu (u) rhythm spectra and oscillatory activity differentiate stuttering from
non-stuttering adults.
AB - Stuttering is linked to sensorimotor deficits related to internal modeling
mechanisms. This study compared spectral power and oscillatory activity of EEG mu
(MU) rhythms between persons who stutter (PWS) and controls in listening and
auditory discrimination tasks. EEG data were analyzed from passive listening in
noise and accurate (same/different) discrimination of tones or syllables in quiet
and noisy backgrounds. Independent component analysis identified left and/or
right MU rhythms with characteristic alpha (alpha) and beta (beta) peaks
localized to premotor/motor regions in 23 of 27 people who stutter (PWS) and 24
of 27 controls. PWS produced MU spectra with reduced beta amplitudes across
conditions, suggesting reduced forward modeling capacity. Group time-frequency
differences were associated with noisy conditions only. PWS showed increased MU
beta desynchronization when listening to noise and early in discrimination
events, suggesting evidence of heightened motor activity that might be related to
forward modeling deficits. PWS also showed reduced MU-alpha synchronization in
discrimination conditions, indicating reduced sensory gating. Together these
findings indicate spectral and oscillatory analyses of MU rhythms are sensitive
to stuttering. More specifically, they can reveal stuttering-related sensorimotor
processing differences in listening and auditory discrimination that also may be
influenced by basal ganglia deficits.
PMID- 28400269
TI - NF-kappaB controls four genes encoding core enzymes of tricarboxylic acid cycle.
AB - NF-kappaB may promote tumor progression by altering cell metabolism. Hence,
finding its target genes that are involved in cell metabolism is helpful for
understanding its role in tumor growth. Here we discovered four metabolism
related target genes of this transcription factor. By analyzing a chromatin
immunoprecipitation followed by deep sequencing (ChIP-Seq) data that
characterizing the global binding sites (BSs) of NF-kappaB RelA in the TNFalpha
stimulated HeLa cells, we found that four genes that encode core enzymes of the
tricarboxylic acid (TCA) cycle, including IDH1, IDH3A, ACO2, and SUCLA2, were
multiply bound by this transcription factor. The subsequent bioinformatic
analysis revealed that the NF-kappaB BSs contained many canonical kappaB
sequences and the NF-kappaB-like DNA-binding motifs. Detection of ChIPed DNA with
polymerase chain reaction (ChIP-PCR) also indicated that the NF-kappaB BSs were
bound by NF-kappaB in both TNFalpha-treated HeLa and HepG2 cells. The reporter
construct showed that the NF-kappaB BSs could activate the luciferase expression
in cells in a NF-kappaB-specific manner. The quantitative PCR and Western blot
detections demonstrated that NF-kappaB could regulate the expressions of IDH1,
IDH3A, and ACO2 genes at both mRNA and protein levels and that of SUCLA2 gene at
mRNA level in the TNFalpha-treated HeLa and HepG2 cells. Based on these
investigations we identified the four genes as new target genes of NF-kappaB. The
finding provides new insights into the role of NF-kappaB in cellular energetic
metabolism, which may be beneficial for understanding the metabolic physiology of
tumor growth.
PMID- 28400270
TI - Differential expression profile of miRNAs in porcine muscle and adipose tissue
during development.
AB - MicroRNAs (miRNAs) are a class of non-coding RNAs that play a crucial regulatory
role in many biological processes. Previous studies have reported miRNAs that are
associated with the growth, differentiation, and proliferation of myocytes and
adipocytes in pigs. However, differences in the miRNA expression profiles between
muscle and adipose tissues during porcine development are unknown. Muscle and
adipose tissues are the two major organs that are crucial for dynamic energy
balance in the development and metabolism. Identification of differential
expression profile of miRNAs will be useful for understanding the regulatory role
of miRNAs in growth, development and evolution of these two tissues, and the
research results will provide theoretical basis to improve meat quality.
Therefore, we applied Hiseq sequencing to profile miRNAs in muscle and adipose
tissues during four development stage at 1, 30, 90 and 240-day-old to explore
their regulatory patterns at critical growth stages of pigs. We slaughtered 6
pigs at each developmental stages (24 pigs in total), respectively, RNA of three
individual pigs were pooled and duplicate samples at each time point were given
to sequence. We obtained a total of 96 million clean reads, and identified 329
known miRNAs and 157 novel miRNAs from all the libraries. We detected 37 miRNAs
that were differentially expressed between porcine muscle and adipose tissues; 17
miRNAs which differentially expressed at 30, 90 and 240-day-old were considered
as core differentially expressed miRNAs, among them, three miRNAs (ssc-miR-128,
133a-5p, -489) were differentially expressed at all four stages. KEGG analysis
revealed the target genes of 17 core differentially expressed miRNAs were
involved in 27 significantly enriched pathways (P<0.01), including the MAPK, Wnt,
TGF-beta, and Notch signaling pathways, which are known to regulate myogenesis or
are related to lipogenesis. 8 and 11 miRNAs were differentially expressed in the
muscle and adipose tissues, respectively, of 30, 90, and 240-day-old pigs
compared with the tissues of 1-day-old pigs. We selected five miRNAs from 17 core
differentially expressed miRNAs to validate the miRNA-seq results by RT-qPCR, the
RT-qPCR expression results corresponded well with those from the miRNA-seq. This
study analyzed differential expression miRNA profiles between porcine skeletal
muscle and adipose tissues during development, and provided valuable information
to investigate the regulation mechanism of functional miRNAs.
PMID- 28400271
TI - Identification and functional characterization of a novel member of low-density
lipoprotein receptor-related protein (LRP)-like family in amphioxus.
AB - Low-density lipoprotein receptor-related protein (LRP) is a group of important
endocytic receptors contributing to binding ligands and maintaining internal
environment. In this study, we identified a soluble LRP-like molecule in the
amphioxus B. japonicum, BjLRP, with an uncharacterized domain structure
combination of LY-EGF-CRD-EGF-CRD. It was mainly expressed in the gill, muscle,
notochord and testis, and was significantly up-regulated following the challenge
with bacteria. Recombinant BjLRP was capable of interacting with both Gram
negative and positive bacteria as well as PAMPs including lipopolysaccharide
(LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN). Interestingly,
recombinant LY peptide was also able to bind to the Gram-negative and positive
bacteria as well as the PAMPs LPS, LTA and PGN. By contrast, none of recombinant
EGF1, EGF2, CRD1 and CRD2 had affinity to the bacteria and the PAMPs. In
addition, BjLRPDeltaLY had no affinity to the PAMPs, although BjLRPDeltaLY showed
slight affinity to the bacteria. These suggest that the interaction of BjLRP with
the bacteria and PAMPs was primarily attributable to the LY domain. It is clear
that BjLRP is a novel pattern recognition protein capable of identifying and
interacting with invading bacteria in amphioxus.
PMID- 28400272
TI - Epigenetic processes in sporadic parathyroid neoplasms.
AB - Parathyroid tumors (PTs) are highly variable in their genetic background.
Increasing evidence demonstrates that endocrine diseases can be caused by
epigenetic alterations. The present review is focused on epigenetic aberrations
related to PTs. DNA methylation, posttranslational histone modification, and
noncoding RNAs are epigenetic mechanisms involved in parathyroid tumorigenesis.
The information in this review has the potential to define epigenetic signatures
associated with PTs for future use as diagnostic markers and lead to the
development of new epigenetic drugs with therapeutic applications for these
tumors. However, several epigenetic aspects regarding the biomarkers involved and
their interactions in tumorigenesis on PTs are still unknown. Key to future
epigenetic research would be a focus on global epigenetic identification of
biomarkers in the different types of PTs, especially in parathyroid carcinoma.
Better understanding may be useful for diagnostic and therapeutic uncertainty.
PMID- 28400274
TI - Characterization of Gnrh/Gnih elements in the olfacto-retinal system and ovary
during zebrafish ovarian maturation.
AB - Gonadotropin releasing hormone (GnRH) is one of the key players of brain
pituitary-gonad axis, exerting overall control over vertebrate reproduction. In
zebrafish, two variants were characterized and named as Gnrh2 and Gnrh3. In this
species, Gnrh3, the hypohysiotropic form, is expressed by neurons of the
olfactory-retinal system, where it is related with food detection,
intra/interspecific recognition, visual acuity and retinal processing modulation.
Previous studies have reported the presence of Gnrh receptors in the zebrafish
retina, but not yet in the zebrafish olfactory epithelium. The current study
analyzed the presence of gnrh2 and gnrh3, their receptors (gnrhr 1,2,3 and 4) and
gnih (gonadotropin inhibitory hormone) transcripts, as well as the Gnrh3 protein
in the olfactory epithelium (OE), olfactory bulb (OB), retina and ovary during
zebrafish ovarian maturation. We found an increase of gnrh receptors transcripts
in the OE at the final stages of ovarian maturation. In the OE, Gnrh3 protein was
detected in the olfactory receptor neurons cilia and in the olfactory nerve
fibers. Interestingly, in the OB, we found an inverse expression pattern between
gnih and gnrh3. In the retina, gnrhr4 mRNA was found in the nuclei of amacrine,
bipolar, and ganglion cells next to Gnrh3 positive fibers. In the ovary, gnrh3,
gnrhr2 and gnrhr4 transcripts were found in perinucleolar oocytes, while gnih in
oocytes at the cortical alveolus stage. Our results suggested that Gnrh/Gnih
elements are involved in the neuromodulation of the sensorial system particularly
at the final stages of maturation, playing also a paracrine role in the ovary.
PMID- 28400275
TI - Mutational analysis employing a phylogenetic mass tree approach in a study of the
evolution of the influenza virus.
AB - A mass based approach has been advanced to enable mutations associated with the
evolution of proteins to be both charted and interrogated using phylogenetic
trees built solely from the masses of peptides generated upon protein
proteolysis. The modified MassTree algorithm identifies and displays all such
mutations and calculates the frequency of a particular mutation across a tree.
Its significance in terms of its position(s) on the tree is scored, where
mutations that occur toward the basis of the tree are weighted more favourably. A
comparison with data generated from a conventional sequence based tree
demonstrates the reliability of mutational analysis employing this approach.
Although illustrated for the study of the evolution of influenza hemagglutinin in
this work, the approach has far broader applicability and can be applied to
investigate the evolution of any organism. In the case of simple microorganisms
this can be achieved even without the separation of component proteins. Given the
central role that mass map or fingerprint data plays in protein identification in
proteomics, this work demonstrates that such data can be successfully employed in
a phylogenetics strategy to better understand and predict future evolutionary
trends from the perspective of functional proteins expressed by the organism.
PMID- 28400276
TI - Optic disk hemorrhage in health and disease.
AB - Optic disk hemorrhage occurs in all age groups from neonates to the elderly.
Optic disk hemorrhage is best known for its association with visual field loss
and progression in patients with glaucoma; however, it may occur in conjunction
with other ocular or systemic conditions as well as in healthy individuals. It
may also be the first sign of a sight-threatening condition. Variations in the
shape, location, and size of the optic disk hemorrhage, as well as associated
ocular and systemic signs or symptoms, may help determine the underlying
pathology. We address the epidemiology, demographics, pathophysiology, clinical
presentations and implications, differential diagnoses, and management of eyes
with optic disk hemorrhage in diseased and healthy subjects.
PMID- 28400273
TI - The role of vitamin D in the endocrinology controlling calcium homeostasis.
AB - Vitamin D and its' metabolites are a crucial part of the endocrine system that
controls whole body calcium homeostasis. The goal of this hormonal control is to
regulate serum calcium levels so that they are maintained within a very narrow
range. To achieve this goal, regulatory events occur in coordination at multiple
tissues, e.g. the intestine, kidney, bone, and parathyroid gland. Production of
the vitamin D endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2 D) is
regulated by habitual dietary calcium intake and physiologic states like growth,
aging, and the menopause. The molecular actions of 1,25(OH)2 D on calcium
regulating target tissues are mediated predominantly by transcription controlled
by the vitamin D receptor. A primary role for 1,25(OH)2 D during growth is to
increase intestinal calcium absorption so that sufficient calcium is available
for bone mineralization. However, vitamin D also has specific actions on kidney
and bone.
PMID- 28400277
TI - High sensitive one-step RT-PCR using MMLV reverse transcriptase, DNA polymerase
with reverse transcriptase activity, and DNA/RNA helicase.
PMID- 28400278
TI - miR-101 suppresses HBV replication and expression by targeting FOXO1 in hepatoma
carcinoma cell lines.
AB - microRNAs (miRNAs) have been identified to participate in the progression of
cancers and in the infection of viruses. miR-101 expression has been found to be
suppressed by HBV, however, the regulatory relationship between miR-101 and HBV
replication remains elusive. In this report, miR-101 was significantly
downregulated in HepG2.2.15 cells with HBV expression. miR-101 overexpression
dramatically suppressed HBV replication and expression. Oppositely,
overexpression of FOXO1 significantly promoted HBV replication and expression.
Moreover, luciferase reporter analysis, qRT-PCR analysis and western blot assay
confirmed that FOXO1 was a functional target of miR-101. Furthermore, restored
FOXO1 expression abolished the inhibitory effect of miR-101 overexpression on HBV
replication and expression in HepG2.2.15 cells. Our data suggested that miR-101
suppressed HBV replication and expression partially by targeting FOXO1, providing
new insights into the molecular mechanisms of miR-101 in HBV-host interactions
and a promising therapeutic target for HBV replication.
PMID- 28400279
TI - SNHG1 lncRNA negatively regulates miR-199a-3p to enhance CDK7 expression and
promote cell proliferation in prostate cancer.
AB - Long noncoding RNAs (lncRNAs) have been reported to play vital roles in the
development of human cancers, but our understandings of most lncRNAs in cancers
are still limited. Recently, accumlating evidences have showed that many RNA
transcripts could function as competing endogenous RNAs (ceRNAs) by competitively
binding common microRNAs. In this study, we demonstrated that a lncRNA, Small
Nucleolar RNA Host Gene 1 (SNHG1), as a ceRNA for miR-199a-3p, played a critical
role in prostate cancer cell proliferation. We found that SNHG1 was aberrantly up
regulated in prostate carcinoma tissues; while, miR-199a-3p was abnormally down
regulated. The level of SNHG1 in prostate cancer was significantly negatively
correlated with that of miR-199a-3p. Our data indicated that SNHG1 could interact
with miR-199a-3p and inhibit the activity of miR-199a-3p in prostate cancer
cells. In addition, miR-199a-3p could target the 3' UTR of CDK7 and suppress CDK7
expression. More importantly, SNHG1 increased CDK7 expression by competitively
binding miR-199a-3p, and then promoted cell proliferation and cell cycle
progression in prostate cancer. Taken together, these findings elucidated a novel
mechanism of prostate cancer progression. Thus, SNHG1 might serve as a potential
target for prostate cancer therapies.
PMID- 28400280
TI - Transcriptional activation of NANOG by YBX1 promotes lung cancer stem-like
properties and metastasis.
AB - Aberrant overexpression of the transcription/translation factor Y-box-binding
protein-1 (YBX1) is associated with non-small cell lung cancer (NSCLC)
aggressiveness. Cancer stem cells (CSCs) contribute to the tumorigenesis and
metastasis of NSCLC. Hitherto, the mechanism by which YBX1 regulates CSCs and
metastasis in NSCLC remains unclear. Here, we demonstrated that YBX1 levels were
elevated in NSCLC tissues and cell lines. Enforced expression of YBX1 promoted
NSCLC cells invasion, sphere forming ability and ALDH1+ population. Conversely,
reduced YBX1 impaired CSC properties of NSCLC cells in vitro and tumor-initiating
frequencies, as well as metastasis in vivo. Importantly, we described a mechanism
whereby YBX1 directly promoted NANOG, a transcription factor, transcriptional
activation. Depletion of NANOG abolished the enhanced ability of invasion and
sphere formation in YBX1 elevated-A549 cells. Collectively, these findings
demonstrate a novel role of YBX1 in maintaining the stemness of CSCs and
metastasis, unveiling YBX1 as promising therapeutic target for NSCLC treatments.
PMID- 28400281
TI - The Pseudomonas transcriptional regulator AlgR controls LipA expression via the
noncoding RNA RsmZ in Pseudomonas protegens Pf-5.
AB - Pseudomonas lipases are well studied enzymes. However, few studies have been
conducted to explore the mechanism underlying the regulation of lipases
expression. AlgR, a global regulator, controls the expression of multiple genes,
regulates bacterial peristalsis, and participates in the regulation of quorum
sensing (QS) system, and so on. In this study, the effect of AlgR on lipase
expression was investigated by knocking out the algR and rsmZ genes or
overexpressing them. It is found out that AlgR can regulate the expression of
lipA at both transcriptional and translational levels, but the transcriptional
level was dominant. AlgR is also able to regulate the expression of
rsmX/rsmY/rsmZ. Additionally, using algR/rsmZ double gene knock-out, it showed
that AlgR could directly bind to the promoter sequence of rsmZ to regulate lipA
activity. In conclusion, this study for the first time indicates that AlgR
directly binds to rsmZ to regulates the expression of lipA via regulating
transcription of rsmZ, and mainly regulates the expression of lipA at
transcriptional level in P. protegens Pf-5.
PMID- 28400282
TI - MicroRNA-153-3p suppress cell proliferation and invasion by targeting SNAI1 in
melanoma.
AB - Malignant melanoma is one of the most common malignancies of the skin cancer and
increasing evidences revealed that microRNAs (miRNAs) exert significant effects
in melanoma. In the present study, the underlying function of microRNA-153-3p
(miR-153-3p) in melanoma was investigated from different levels, including cell
level, protein level and gene level. Our results showed that expression of miR
153-3p was lower in melanoma tissues and melanoma cells compared with the para
tumor tissue and normal melanocytes. The overexpression of miR-153-3p inhibited
the cell proliferation and invasion, at the same time promoted cell apoptosis.
Moreover, we identified that snail family transcriptional repressor 1 (SNAI1) is
the direct target of miR-153-3p, and there is a negative correlation between miR
153-3p level and SNAI1 expression. In summary, we presented the evidences that
miR-153-3p may act as a tumor suppressor by down-regulating the expression of
SNAI1 in melanoma and miR-153-3p might be a potential biomarker in the diagnosis
and treatment of malignant melanoma.
PMID- 28400283
TI - The role of GluN2B-containing NMDA receptors in short- and long-term fear recall.
AB - N-methyl-d-aspartate (NMDA) receptors are crucial synaptic elements in long-term
memory formation, including the associative learning of fearful events. Although
NMDA blockers were consistently shown to inhibit fear memory acquisition and
recall, the clinical use of general NMDA blockers is hampered by their side
effects. Recent studies revealed significant heterogeneity in the distribution
and neurophysiological characteristics of NMDA receptors with different GluN2
(NR2) subunit composition, which may have differential role in fear learning and
recall. To investigate the specific role of NMDA receptor subpopulations with
different GluN2 subunit compositions in the formation of lasting traumatic
memories, we contrasted the effects of general NMDA receptor blockade with GluN2A
, GluN2B-, and GluN2C/D subunit selective antagonists (MK-801, PEAQX, Ro25-6981,
PPDA, respectively). To investigate acute and lasting consequences, behavioral
responses were investigated 1 and 28days after fear conditioning. We found that
MK-801 (0.05 and 0.1mg/kg) decreased fear recall at both time points. GluN2B
receptor subunit blockade produced highly similar effects, albeit efficacy was
somewhat smaller 28days after fear conditioning. Unlike MK-801, Ro25-6981 (3 and
10mg/kg) did not affect locomotor activity in the open-field. In contrast, GluN2A
and GluN2C/D blockers (6 and 20mg/kg PEAQX; 3 and 10mg/kg PPDA, respectively) had
no effect on conditioned fear recall at any time point and dose. This sharp
contrast between GluN2B- and other subunit-containing NMDA receptor function
indicates that GluN2B receptor subunits are intimately involved in fear memory
formation, and may provide a novel pharmacological target in post-traumatic
stress disorder or other fear-related disorders.
PMID- 28400284
TI - Transcriptome, antioxidant enzyme activity and histopathology analysis of
hepatopancreas from the white shrimp Litopenaeus vannamei fed with aflatoxin
B1(AFB1).
AB - Aflatoxin produced by Aspergillus flavus or Aspergillus parasiticus fungi during
grain and feed processing and storage. Aflatoxins cause severe health problems
reducing the yield and profitability of shrimp cultures. We sought to understand
the interaction between shrimp immunity and aflatoxin B1 (AFB1), analyzing
transcriptome expression, antioxidant enzyme activity, and histological features
of the hepatopancreas of shrimp fed with AFB1. From over 4 million high-quality
reads, de novo unigene assembly produced 103,644 fully annotated genes. A total
of 1024 genes were differentially expressed in shrimp fed with AFB1, being
involved in functions, such as peroxidase metabolism, signal transduction,
transcriptional control, apoptosis, proteolysis, endocytosis, and cell adhesion
and cell junction. Upon AFB1 challenge, there were severe histological
alterations in shrimp hepatopancreas. AFB1 challenge increased the activity of
several antioxidant enzymes. Our data contribute to improve the current
understanding of host-AFB1 interaction, providing an abundant source for
identification of novel genes.
PMID- 28400285
TI - Development and evaluation of a cedrol-loaded nanostructured lipid carrier system
for in vitro and in vivo susceptibilities of wild and drug resistant Leishmania
donovani amastigotes.
AB - : Leishmaniasis is an epidemic in various countries, and the parasite Leishmania
donovani is developing resistance against available drugs. In the present study
the antileishmanial action of cedrol was evaluated in vitro and in vivo. Activity
potentiation was achieved via nanostructured lipid carrier (NLC) complexation of
cedrol. Cedrol-loaded NLC was prepared through the hot-melting emulsification
ultrasonication method. The cedrol- NLC prepared did not require the use of any
organic solvents. The characterization of NLC-C1 and NLC-C2 revealed that
particle size was 46.62nm and 54.73nm for 3.85%, and 7.48% drug loading,
respectively and negative charge of -19.2mV and -23.7mV. The cedrol-loaded NLC
were found to be spherical with a smooth surface. Drug-carrier interactions were
clearly visualized in FT-IR studies. Incorporation of cedrol in NLC was
ascertained in DSC and XRD analysis. Antileishmanial activities of free cedrol
and cedrol-NLC were performed against L. donovani wild-type, sodium
stibogluconate, paromomycin and field isolated resistant strains in axenic
amastigotes and amastigotes in macrophage model. Coumarin-6 loaded NLC
nanoparticles were assessed for macrophage internalization in confocal
microscopic studies. Cedrol showed significant antileishmanial activity in wild
type (IC50=1.5MUM), sodium stibogluconate resistant (IC50=2MUM), paromomycin
resistant (IC50=1.8MUM) and field isolated resistant (IC50=1.35MUM) strains in
macrophage together with cytotoxicity (CC50=74MUM) in mouse peritoneal macrophage
cells. Incorporation of cedrol in NLC-C2 resulted in 2.1-fold and 2-fold increase
in selectivity indexes (CC50/IC50) for wild-type and drug resistant strains,
respectively. In addition, in vivo studies revealed that bioactivity of NLC-C2
were 2.3 to 3.8-fold increased in wild-type and 3 to 4.9-fold increased in drug
resistant strains when compared with free cedrol; administered orally in mouse
leishmaniasis model. Overall, NLC-C2 showed superior antileishmanial activity to
free cedrol and miltefosine in oral dose. These findings support the use of NLCs
for oral delivery of poorly water-soluble antileishmanial drugs in treatment of
leishmaniasis. CHEMICAL COMPOUNDS: Cedrol (PubChem CID: 65575); Compritol(r) 888
ATO (PubChem CID: 62726); Triolein (PubChem CID: 5497163); Pluronic F68 (PubChem
CID: 24751); Soya lecithin (PubChem CID: 57369748); Sodium deoxycholate (PubChem
CID: 23668196); Miltefosine (PubChem CID: 3599); Paromomycin (PubChem CID:
165580); Amphotericin B (PubChem CID: 5280965); Sodium stibogluconate (PubChem
CID: 16683012).
PMID- 28400286
TI - Increased oxidative stress and cytokinesis-block micronucleus cytome assay
parameters in pregnant women with gestational diabetes mellitus and gestational
arterial hypertension.
AB - We investigated whether gestational diabetes mellitus (GDM) and gestational
arterial hypertension (GH) are associated with increased oxidative stress and DNA
damage. Study included 3 groups of pregnant women (GDM, GH and control). DNA
damage biomarkers (micronuclei MNi, nucleoplasmic bridges NPBs and nuclear buds
NBUDs) were assessed by cytokinesis-block micronucleus cytome assay. Oxidative
stress levels were evaluated by analyzing malondialdehyde equivalents (TBARS) and
8-hydroxy-2'-deoxyguanosine (8-OHdG). Genotoxic effect of methyldopa, drug used
to treat GH, was evaluated in in vitro experiment. TBARS levels, MNi, NPBs and
NBUDs frequencies were significantly increased in both GDM and GH group.
Concentrations of 8-OHdG were significantly higher in GDM than in other groups.
Since methyldopa did not affect MNi, NPBs and NBUDs frequencies, nor TBARS and 8
OHdG levels, we concluded that methyldopa has no genotoxic effect. Thus, even
when hyperglycemia or hypertension are present only during pregnancy they induce
oxidative stress, DNA damage and chromosomal aberrations.
PMID- 28400287
TI - Anti-inflammatory and vasoconstrictive properties of Potentilla erecta - A
traditional medicinal plant from the northern hemisphere.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla erecta (L.) Raeusch is a medicinal
plant of the Northern hemisphere belonging to the plant family of roses
(Rosaceae). It has traditionally been used to treat inflammatory disorders of the
skin and mucous membranes as well as chronic diarrhea. AIM OF THE STUDY: In the
present study we analyzed the anti-inflammatory and vasoconstrictive effect of a
Potentilla erecta extract (PE) and questioned if PE is similar effective as mild
corticosteroids. Then we analyzed if PE acts in the skin via a similar mode of
action as corticosteroids. MATERIAL AND METHODS: The anti-inflammatory effect of
PE was analyzed in irradiated HaCaT keratinocytes by measuring the formation of
IL-6 and PGE2. Additionally the effect of PE on TNF-alpha induced NF-kappaB
activation was determined. As the anti-inflammatory effect of corticosteroids
correlates with their vasoconstrictive properties we tested if PE displays also
vasoconstriction. Therefore we performed an occlusive patch test and a collagen
contraction assay. Furthermore the binding of PE to the glucocorticoid receptor
was determined with stainings and reporter assays. The interaction of PE on the
nitric oxide (NO) content was examined with radical scavenging and endothelial NO
synthase (eNOS) reporter assays. RESULTS: In irradiated or TNF-alpha stimulated
HaCaT cells the formation of IL-6 and PGE2 or NF-kappaB activation was strongly
reduced by PE. Furthermore PE showed a blanching effect comparable to
hydrocortisone. However, in contrast to glucocorticoids, PE did not cause nuclear
translocation of the glucocorticoid receptor in HaCaT cells. The blanching effect
of PE was at least partly attributable to a scavenging effect of NO and
inhibition of eNOS. CONCLUSIONS: PE displays anti-inflammatory and
vasoconstrictive effects and might therefore be beneficial for the topical
treatment of inflammatory skin disorders.
PMID- 28400288
TI - Ocimum gratissimum L. leaf flavonoid-rich fraction suppress LPS-induced
inflammatory response in RAW 264.7 macrophages and peritonitis in mice.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum gratissimum L. is a herbaceous plant that
has been reported in several ethnopharmacological surveys as a plant readily
accessible to the communities and widely used for the treatment of inflammatory
diseases. The main goal of this study was to investigate the in vitro and in vivo
anti-inflammatory activity and mechanism of action of the ethylacetate fraction
of O. gratissimum leaf (EAFOg) and to chemically characterize this fraction.
MATERIALS AND METHODS: EAFOg was obtained from a sequential methanol extract. The
safety profile was evaluated on RAW 264.7 cells, using the alamarBlue(r) assay.
Phenolic contents were determined by spectrophotometry, and metabolites
quantified by high performance liquid chromatography. The anti-inflammatory
activity of EAFOg and its ability to acts on leucocytes infiltration,
inflammatory mediators as NO, IL-1beta, TNF-alpha, and IL-10 in
lipopolysaccharide-induced peritonitis in mice and LPS-stimulated RAW 264.7
macrophage were evaluated. In addition, the anti-inflammatory activity of EAFOg
was also investigated in arachidonic acid-related enzymes. RESULTS: Total
phenolic and flavonoid contents of EAFOg were 139.76+/-1.07mg GAE/g and 109.95+/
0.05mg RE/g respectively. HPLC analysis revealed the presence of rutin, ellagic
acid, myricetin and morin. The fraction exhibited no cytotoxic effects on the RAW
264.7 cells. The EAFOg (10, 50 and 200mg/kg) significantly reduced (p<0.05)
neutrophils (38.8%, 58.9%, and 66.5%) and monocytes (38.9%, 58.0% and 72.8%) in
LPS-induced peritonitis. Also, EAFOg (5, 20 and 100ug/mL) produced significant
reduction in NO, IL-1beta, and TNF-alpha in RAW 264.7 cells. However, IL-10 level
was not affected by the EAFOg, and it preferentially inhibits COX-2 (IC50
=48.86+/-0.02ug/mL) than COX-1 and 15-LO (IC50 >100ug/mL). CONCLUSION: The
flavonoid-rich fraction of O. gratissimum leaves demonstrated anti-inflammatory
activity via mechanisms that involves inhibition of leucocytes influx, NO, IL
1beta, and TNF-alpha in vivo and in vitro, thus supporting its therapeutic
potential in slowing down inflammatory processes in chronic diseases.
PMID- 28400289
TI - Mathematical modelling of liquid transport in swelling pharmaceutical immediate
release tablets.
AB - Oral dosage forms are an integral part of modern health care and account for the
majority of drug delivery systems. Traditionally the analysis of the dissolution
behaviour of a dosage form is used as the key parameter to assess the performance
of a drug product. However, understanding the mechanisms of disintegration is of
critical importance to improve the quality of drug delivery systems. The
disintegration performance is primarily impacted by the hydration and subsequent
swelling of the powder compact. Here we compare liquid ingress and swelling data
obtained using terahertz pulsed imaging (TPI) to a set of mathematical models.
The interlink between hydration kinetics and swelling is described by a model
based on Darcy's law and a modified swelling model based on that of Schott. Our
new model includes the evolution of porosity, pore size and permeability as a
function of hydration time. Results obtained from two sets of samples prepared
from pure micro-crystalline cellulose (MCC) indicate a clear difference in
hydration and swelling for samples of different porosities and particle sizes,
which are captured by the model. Coupling a novel imaging technique, such as TPI,
and mathematical models allows better understanding of hydration and swelling and
eventually tablet disintegration.
PMID- 28400290
TI - Downstream drug product processing of itraconazole nanosuspension: Factors
influencing drug particle size and dissolution from nanosuspension-layered beads.
AB - There is more research required to broaden the knowledge on the downstream
processing of nanosuspensions into solid oral dosage forms, especially for coated
nanosuspensions onto beads as carriers. This study focuses on bead layering as
one approach to solidify nanosuspensions. The aim was to systematically
investigate the influence of type of coating polymer (HPMC VLV vs. copovidone),
bead material and bead size (sugar vs. MCC, and small vs. large) and coating
thickness (50%-150% layering level) on the properties of a dried itraconazole
nanosuspension. A stable itraconazole nanosuspension with a mean particle size
below 200nm was prepared and a ratio of itraconazole and coating polymer of
around 1:1 was identified. XRD and DSC scans revealed that itraconazole remained
mostly crystalline after the bead layering process. The fastest dissolution rate
was achieved using the small bead size, sugar beads, HPMC VLV as film-forming
polymer and lowest layering level, with the best formulation releasing 94.1% (+/
3.45% SD) within the first 5min. A deterioration of the release profile with
increasing layering level was only observed for MCC beads and was more pronounced
when copovidone was used as a coating polymer. It was observed that bead layering
is a suitable method to process an itraconazole nanosuspension into a solid form
without compromising release.
PMID- 28400291
TI - Unmet clinical needs in the treatment of systemic fungal infections: The role of
amphotericin B and drug targeting.
AB - Recently an increase in both the prevalence and incidence of invasive fungal
infections have been reported. The number of fungal species that can cause
systemic mycoses are higher and current antifungal therapies are still far from
ideal. The emergence of antifungal resistances has a major clinical impact when
using azoles and echinocandins leading to possible treatment failure and
ultimately putting the patient's life at risk. Amphotericin B can play a key role
in treating severe invasive mycoses as the incidence of antifungal resistance is
very low combined with a high efficacy against a wide range of fungi. However,
the use of this drug is limited due to its high toxicity and the infusion-related
side effects often necessitating patient hospitalisation. New medicines based on
lipid-based systems have been commercialised in the last decade, these treatments
are able to reduce the toxicity of the drug but intravenous administration is
still required. An oral or topically self-administered amphotericin B formulation
can overcome these challenges, however such a product is not yet available.
Several drug delivery systems such as cochleates, nanoparticulate and self
emulsifying systems are under development in order to enhance the solubility of
the drug in aqueous media and promote oral absorption and cutaneous permeation
across the skin. In this review, the type of drug delivery system and the effect
of particle size on efficacy, toxicity and biodistribution will be discussed.
PMID- 28400292
TI - Is Takotsubo Syndrome a benign condition?
PMID- 28400294
TI - The distribution of P-values in medical research articles suggested selective
reporting associated with statistical significance.
AB - OBJECTIVES: Published P-values provide a window into the global enterprise of
medical research. The aim of this study was to use the distribution of published
P-values to estimate the relative frequencies of null and alternative hypotheses
and to seek irregularities suggestive of publication bias. STUDY DESIGN AND
SETTING: This cross-sectional study included P-values published in 120 medical
research articles in 2016 (30 each from the BMJ, JAMA, Lancet, and New England
Journal of Medicine). The observed distribution of P-values was compared with
expected distributions under the null hypothesis (i.e., uniform between 0 and 1)
and the alternative hypothesis (strictly decreasing from 0 to 1). P-values were
categorized according to conventional levels of statistical significance and in
one-percent intervals. RESULTS: Among 4,158 recorded P-values, 26.1% were highly
significant (P < 0.001), 9.1% were moderately significant (P >= 0.001 to < 0.01),
11.7% were weakly significant (P >= 0.01 to < 0.05), and 53.2% were
nonsignificant (P >= 0.05). We noted three irregularities: (1) high proportion of
P-values <0.001, especially in observational studies, (2) excess of P-values
equal to 1, and (3) about twice as many P-values less than 0.05 compared with
those more than 0.05. The latter finding was seen in both randomized trials and
observational studies, and in most types of analyses, excepting heterogeneity
tests and interaction tests. Under plausible assumptions, we estimate that about
half of the tested hypotheses were null and the other half were alternative.
CONCLUSION: This analysis suggests that statistical tests published in medical
journals are not a random sample of null and alternative hypotheses but that
selective reporting is prevalent. In particular, significant results are about
twice as likely to be reported as nonsignificant results.
PMID- 28400295
TI - PhiC31 integrase can improve the efficiency of different construct designs for
monoclonal antibody expression in CHO cells.
AB - OBJECTIVES: Several types of expression vectors have been used for recombinant
protein expression in Chinese hamster ovary cells (CHO) which usually result in
variable and unstable levels of expression. METHODS AND RESULTS: In this study,
we have compared the mAb0014 expression level of single ORF/IRES vector and dual
ORF vector in the presence and absence of phiC31 integrase targeting system. Both
expression vectors contain an elongation factor 1alpha (EF1alpha) promoter
upstream of LC and harboring an attB site. CHO-S cells were co-transfected with
single ORF/IRES or dual ORF vectors along with a phiC31 integrase expression
vector which can catalyze recombination between attB site and pseudo-attP sites
presented in the mammalian genome. Our results demonstrated that dual ORF vector
in the presence of phiC31 integrase expression vectors (+FC31 2P) generated more
recombinant antibody in comparison to its negative control (-FC31 2P). Moreover,
both of +FC31 2P and -FC31 2P cell pools yield higher recombinant protein in
comparison to single ORF/IRES vector (FC31 IRES) cell pools. Stability of
expression in phiC31 co-transfected cell pools (+FC31 2P and +FC31 IRES) had no
considerable changes. CONCLUSIONS: Our results indicated that the dual ORF vector
using integrase can support the generation of cell lines with stable transgene
expression at an elevated mAb relative to single ORF/IRES vector.
PMID- 28400293
TI - The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain.
AB - : The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally
heterogeneous region and a key node of several brain networks, implicated in
cognitive, affective, and sensory processing. As such, the DLPFC is commonly
activated in experimental pain studies, and shows abnormally increased function
in chronic pain populations. Furthermore, several studies have shown that some
chronic pains are associated with decreased left DLPFC gray matter and that
successful interventions can reverse this structural abnormality. In addition,
studies have indicated that noninvasive stimulation of the left DLPFC effectively
treats some chronic pains. In this article, we review the neuroimaging literature
regarding the role of the DLPFC and its potential as a therapeutic target for
chronic pain conditions, including studies showing the involvement of the DLPFC
in encoding and modulating acute pain and studies demonstrating the reversal of
DLPFC functional and structural abnormalities after successful interventions for
chronic pain. We also review studies of noninvasive brain stimulation of the
DLPFC showing acute pain modulation and some effectiveness as a treatment for
certain chronic pain conditions. We further discuss the network architecture of
the DLPFC, and postulate mechanisms by which DLPFC stimulation alleviates chronic
pain. Future work testing these mechanisms will allow for more effective
therapies. PERSPECTIVE: The structure and function of the DLPFC is abnormal in
some chronic pain conditions. Upon successful resolution of pain, these
abnormalities are reversed. Understanding the underlying mechanisms and the role
of this region can lead to the development of an effective therapeutic target for
some chronic pain conditions.
PMID- 28400296
TI - Recombinant expression and purification of the RNA-binding LARP6 proteins from
fish genetic model organisms.
AB - The RNA-binding proteins that comprise the La-related protein (LARP) superfamily
have been implicated in a wide range of cellular functions, from tRNA maturation
to regulation of protein synthesis. To more expansively characterize the
biological function of the LARP6 subfamily, we have recombinantly expressed the
full-length LARP6 proteins from two teleost fish, platyfish (Xiphophorus
maculatus) and zebrafish (Danio rerio). The yields of the recombinant proteins
were enhanced to >2 mg/L using a tandem approach of an N-terminal His6-SUMO tag
and an iterative solubility screening assay to identify structurally stabilizing
buffer components. The domain topologies of the purified fish proteins were
probed with limited proteolysis. The fish proteins contain an internal, protease
resistant 40 kDa domain, which is considerably more stable than the comparable
domain from the human LARP6 protein. The fish proteins are therefore a lucrative
model system in which to study both the evolutionary divergence of this family of
La-related proteins and the structure and conformational dynamics of the domains
that comprise the LARP6 protein.
PMID- 28400297
TI - Characterization of EccA3, a CbbX family ATPase from the ESX-3 secretion pathway
of M. tuberculosis.
AB - EccA family proteins are conserved components of ESX secretion pathways in M.
tuberculosis H37Rv. Here, we report the characterization of EccA3 (Rv0282), a
CbbX family AAA (ATPases Associated with diverse cellular Activities) protein
from the ESX-3 pathway that is required for in vitro growth of mycobacteria,
secretion of virulence factors, and acquisition of iron and zinc. EccA3 is a
thermostable ATPase with a molecular weight of ~68kDa. It exists as a dodecamer
in the apo form and associates as a hexamer in the presence of ATP. Its C
terminal region consists of a CbbX-like AAA-domain while the N-terminal region
contains a tetratricopeptide repeat (TPR) domain with lower homology to other
EccA-type proteins. Further, the C-terminal domain functions as the
oligomerization domain and also exhibits ATPase activity. Mutational analysis,
steady state kinetics and molecular docking studies identify R573 as the
important 'sensor arginine' and R505 as an 'arginine finger' in EccA3. Dynamic
fluorescence quenching experiments suggest that the N-terminal domain moves
closer to the C-terminal domain upon ATP-binding. The ATP-dependent 'open-close'
relative movements of the two domains might help EccA3 interaction and secretion
of essential virulence factors.
PMID- 28400298
TI - Adverse Effect of Post-Discharge Care Fragmentation on Outcomes after
Readmissions after Liver Transplantation.
AB - BACKGROUND: Post-discharge surgical care fragmentation is defined as readmission
to any hospital other than the hospital at which surgery was performed. The
objective of this study was to assess the impact of fragmented readmissions
within the first year after orthotopic liver transplantation (OLT). STUDY DESIGN:
The Healthcare Cost and Utilization Project State Inpatient Databases for Florida
and California from 2006 to 2011 were used to identify OLT patients. Post
discharge fragmentation was defined as any readmission to a non-index hospital,
including readmitted patients transferred to the index hospital after 24 hours.
Outcomes included adverse events, defined as 30-day mortality and 30-day
readmission after a fragmented readmission. All statistical analyses considered a
hierarchical data structure and were performed with multilevel, mixed-effects
models. RESULTS: We analyzed 2,996 patients with 7,485 readmission encounters at
299 hospitals; 1,236 (16.5%) readmissions were fragmented. After adjustment for
age, sex, readmission reason, index liver transplantation cost, readmission
length of stay, number of previous readmissions, and time from transplantation,
post-discharge fragmentation increased the odds of both 30-day mortality (odds
ratio [OR] = 1.75; 95% CI 1.16 to 2.65) and 30-day readmission (OR = 2.14; 95% CI
1.83 to 2.49). Predictors of adverse events after a fragmented readmission
included increased number of previous readmissions (OR = 1.07; 95% CI 1.01 to
1.14) and readmission within 90 days of OLT (OR = 2.19; 95% CI 1.61 to 2.98).
CONCLUSIONS: Post-discharge fragmentation significantly increases the risk of
both 30-day mortality and subsequent readmission after a readmission in the first
year after OLT. More inpatient visits before a readmission and less time elapsed
from index surgery increase the odds of an adverse event after discharge from a
fragmented readmission. These parameters could guide transfer decisions for
patients with post-discharge fragmentation.
PMID- 28400299
TI - Strategies for Identifying and Closing the Gender Salary Gap in Surgery.
PMID- 28400301
TI - Breakfast consumption and depressive mood: A focus on socioeconomic status.
AB - Skipping breakfast can be potentially harmful because breakfast consumption is
considered one of the important health-related behaviors that benefit physical
and mental health. As the rate of depression has increased recently, we
investigated the association between the frequency of eating breakfast and
depression in adults. We obtained the data from the 2013 Korean Community Health
Survey; a total of 207,710 survey participants aged 20 years or over were
studied. Participants were categorized into three groups by the frequency of
breakfast consumption as follows: "seldom," "sometimes," and "always." We
performed a multiple logistic regression to investigate the association between
breakfast consumption and depressive mood. Subgroup analyses were conducted by
stratifying socioeconomic variables controlling for variables known to be
associated with depressive symptoms. Participants who had breakfast seldom or
sometimes had higher depressive symptoms than those who always ate breakfast
("seldom": OR = 1.43, 95% CI 1.36-1.52; "sometimes": OR = 1.32, 95% CI 1.23
1.40). Subgroup analyses showed that this association was more marked in those
who were 80 years or older, those who had low household income, or those with
elementary school education level or less. The result of this study suggests that
lack of breakfast consumption is associated with depression among adults with
different socioeconomic factors.
PMID- 28400300
TI - Neoadjuvant Locoregional Therapy and Recurrent Hepatocellular Carcinoma after
Liver Transplantation.
AB - BACKGROUND: Neoadjuvant locoregional therapies (LRTs) have been widely used to
reduce tumor burden or to downstage hepatocellular carcinoma (HCC) before
orthotopic liver transplantation (OLT). We examined the impact of LRT response on
HCC recurrence after OLT. STUDY DESIGN: We performed a retrospective study of 384
patients with HCC treated by OLT. Tumor necrosis was determined by pathologic
evaluation. The vascular and lymphatic vessels were localized by
immunofluorescence staining in formalin-fixed, paraffin-embedded tissue;
expressions of vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3
were analyzed by Western blot. Plasma vascular endothelial growth factor (VEGF)-A
and VEGF-C levels of a consecutive cohort of 171 HCC patients were detected by
ELISA. RESULTS: Of the 384 patients with HCC, 268 had undergone
pretransplantation neoadjuvant LRTs. Patients with no tumor necrosis (n = 58;
5.2% recurrence) or complete tumor necrosis (n = 70; 6.1% recurrence) had
significantly lower 5-year recurrence rates than those with partial tumor
necrosis (n = 140; 22.6% recurrence; p < 0.001). Lymphatic metastases were
significantly more numerous in patients with partial tumor necrosis than in those
without tumor necrosis after OLT (p < 0.001). With immunofluorescence staining of
peritumor zone, lymphatics were visualized around partially necrotic tumors, but
not around tumors without necrosis. Plasma levels of VEGF-A and VEGF-C were
elevated significantly in patients with evidence of tumor necrosis (n = 102)
compared with those without necrosis (n = 69; p < 0.001). By Western blot, VEGFR
2 and VEGFR-3 expression in the peritumoral tissue associated with partially
necrotic tumors was significantly higher than in peritumoral tissue of non
necrosis tumors (n = 3/group, p < 0.020 and p < 0.006, respectively).
CONCLUSIONS: Locoregional therapy-induced or spontaneous partially necrotic HCC
was associated with increased risk of lymphatic metastases compared with tumors
with no or complete tumor necrosis. Anti-lymphangiogenic agents with neoadjuvant
LRTs can decrease the pattern of lymphatic metastasis after OLT.
PMID- 28400302
TI - Decreased comfort food intake and allostatic load in adolescents carrying the
A3669G variant of the glucocorticoid receptor gene.
AB - BACKGROUND: The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid
receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to
glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated
in increased intake of palatable foods, which can lead to the metabolic syndrome
and obesity. We hypothesized that presence of the G variant of the A3669G SNP
would affect preferences for palatable foods and alter metabolic, behavioural,
and neural outcomes. METHODS: One hundred thirty-one adolescents were genotyped
for the A3669G polymorphism, underwent anthropometric assessment and nutritional
evaluations, and completed behavioural measures. A subsample of 74 subjects was
followed for 5 years and performed a brain functional magnetic resonance imaging
(fMRI) paradigm to verify brain activity in response to food cues. RESULTS: Sugar
and total energy consumption were lower in A3669G G allele variant carriers. On
follow-up, this group also had reduced serum insulin concentrations, increased
insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample
sizes (31/37 participants non-G allele carriers/total), our imaging data analysis
failed to find whole brain-corrected significant results in between-group t
tests. CONCLUSION: These results highlight that a genetic variation in the GR
gene is associated, at the cellular level, with significant reduction in GC
sensitivity, which, at cognitive and behavioural levels, translates to altered
food intake and emotional stress response. This genetic variant might play a
major role in decreasing risk for metabolic and psychiatric diseases.
PMID- 28400303
TI - Infant feeding and child fussy eating: The Generation R Study.
AB - Fussy/picky eating - i.e. consistently avoiding certain foods - is common in
childhood and can be worrisome for parents. Repeated exposure to various flavors
as occurs in breastmilk and early exposure to complementary feeding may increase
food acceptance and thereby decrease fussy eating. This study examines the
associations between infant feeding and child fussy eating in 4779 participants
of Generation R, a Dutch population-based cohort. Breastfeeding initiation and
continuation, and timing of complementary feeding were assessed by questionnaires
at 2, 6, and 12 months. The food fussiness scale of the Children's Eating
Behaviour Questionnaire was administered at 4 years. Linear regression analyses
were performed, adjusted for confounders. Children who were never breastfed did
not differ in fussy eating frequency from children breastfed for 6 months or
longer. However, children who were breastfed for less than 2 months had a 0.70
points higher food fussiness sum-score (95%CI:0.27; 1.12) than children breastfed
for 6 months or longer. An earlier introduction of vegetables was associated with
less fussy eating behavior (p-for-trend:0.005). Particularly children who were
introduced to vegetables between 4 and 5 months had a 0.60 point lower food
fussiness score (95%CI: 1.06;-0.15) than children introduced to vegetables after
6 months. An early introduction to fruits or any solids was not significantly
related to fussy eating, although the effect estimates were in the same direction
as for introducing vegetables early. Results suggest that breastfeeding does not
predict fussy eating. However, introducing vegetables into a child's diet before
5 months might be protective against fussy eating, although future research
should account for parents' own fussy eating.
PMID- 28400304
TI - Parent Preferences and Perceptions of Milliliters and Teaspoons: Role of Health
Literacy and Experience.
AB - BACKGROUND AND OBJECTIVES: A recent American Academy of Pediatrics policy
statement recommends milliliter-exclusive dosing for pediatric liquid
medications. Little is known about parent preferences regarding units,
perceptions about moving to milliliters only, and the role of health literacy and
prior milliliter-dosing experience. METHODS: Cross-sectional analysis of data
collected as part of a randomized controlled study in 3 urban pediatric clinics
(SAFE Rx for Kids study). English- and Spanish-speaking parents (n = 493) of
children aged <=8 years were randomized to 1 of 4 study arms and given labels and
dosing tools which varied in label instruction format (text plus pictogram, text
only) and units (milliliter only ["mL"], milliliter/teaspoon ["mL"/"tsp"]).
Outcomes included teaspoon preference in dosing instructions and perceived
difficulty with milliliter-only dosing. The predictor variable was health
literacy (Newest Vital Sign; low [0-1], marginal [2-3], adequate [4-6]). The
mediating variable was prior milliliter-dosing experience. RESULTS: Over two
thirds of parents had low or marginal health literacy. The majority (>70%)
preferred to use milliliters, perceived milliliter-only dosing to be easy, and
had prior milliliter-dosing experience; 11.5% had a teaspoon preference, 18.1%
perceived milliliter-only dosing will be difficult, and 17.7% had no prior
milliliter-dosing experience. Parents with lower health literacy had a higher
odds of having a teaspoon preference (low vs adequate: adjusted odds ratio [AOR]
= 2.9 [95% confidence interval [CI] 1.3-6.2]), and greater odds of perceiving
difficulty with milliliter-only dosing (low vs adequate: AOR = 13.9 [95% CI 4.8
40.6], marginal vs adequate: AOR = 7.1 [95% CI 2.5-20.4]). Lack of experience
with milliliter dosing partially mediated the impact of health literacy.
CONCLUSIONS: Most parents were comfortable with milliliter-only dosing. Parents
with low health literacy were more likely to perceive milliliter-only dosing to
be difficult; educational efforts will need to target this group to ensure safe
medication use.
PMID- 28400305
TI - Excessive duration of intrauterine balloon placement.
PMID- 28400306
TI - Can 3-dimensional power Doppler indices improve the prenatal diagnosis of a
potentially morbidly adherent placenta in patients with placenta previa?
AB - BACKGROUND: Traditionally, 2-dimensional ultrasound parameters have been used for
the diagnosis of a suspected morbidly adherent placenta previa. More objective
techniques have not been well studied yet. OBJECTIVE: The objective of the study
was to determine the ability of prenatal 3-dimensional power Doppler analysis of
flow and vascular indices to predict the morbidly adherent placenta objectively.
STUDY DESIGN: A prospective cohort study was performed in women between 28 and 32
gestational weeks with known placenta previa. Patients underwent a two
dimensional gray-scale ultrasound that determined management decisions. 3
Dimensional power Doppler volumes were obtained during the same examination and
vascular, flow, and vascular flow indices were calculated after manual tracing of
the viewed placenta in the sweep; data were blinded to obstetricians. Morbidly
adherent placenta was confirmed by histology. Severe morbidly adherent placenta
was defined as increta/percreta on histology, blood loss >2000 mL, and >2 units
of PRBC transfused. Sensitivities, specificities, predictive values, and
likelihood ratios were calculated. Student t and chi2 tests, logistic regression,
receiver-operating characteristic curves, and intra- and interrater agreements
using Kappa statistics were performed. RESULTS: The following results were found:
(1) 50 women were studied: 23 had morbidly adherent placenta, of which 12 (52.2%)
were severe morbidly adherent placenta; (2) 2-dimensional parameters diagnosed
morbidly adherent placenta with a sensitivity of 82.6% (95% confidence interval,
60.4-94.2), a specificity of 88.9% (95% confidence interval, 69.7-97.1), a
positive predictive value of 86.3% (95% confidence interval, 64.0-96.4), a
negative predictive value of 85.7% (95% confidence interval, 66.4-95.3), a
positive likelihood ratio of 7.4 (95% confidence interval, 2.5-21.9), and a
negative likelihood ratio of 0.2 (95% confidence interval, 0.08-0.48); (3) mean
values of the vascular index (32.8 +/- 7.4) and the vascular flow index (14.2 +/-
3.8) were higher in morbidly adherent placenta (P < .001); (4) area under the
receiver-operating characteristic curve for the vascular and vascular flow
indices were 0.99 and 0.97, respectively; (5) the vascular index >=21 predicted
morbidly adherent placenta with a sensitivity and a specificity of 95% (95%
confidence interval, 88.2-96.9) and 91%, respectively (95% confidence interval,
87.5-92.4), 92% positive predictive value (95% confidence interval, 85.5-94.3),
90% negative predictive value (95% confidence interval, 79.9-95.3), positive
likelihood ratio of 10.55 (95% confidence interval, 7.06-12.75), and negative
likelihood ratio of 0.05 (95% confidence interval, 0.03-0.13); and (6) for the
severe morbidly adherent placenta, 2-dimensional ultrasound had a sensitivity of
33.3% (95% confidence interval, 11.3-64.6), a specificity of 81.8% (95%
confidence interval, 47.8-96.8), a positive predictive value of 66.7% (95%
confidence interval, 24.1-94.1), a negative predictive value of 52.9% (95%
confidence interval, 28.5-76.1), a positive likelihood ratio of 1.83 (95%
confidence interval, 0.41-8.11), and a negative likelihood ratio of 0.81 (95%
confidence interval, 0.52-1.26). A vascular index >=31 predicted the diagnosis of
a severe morbidly adherent placenta with a 100% sensitivity (95% confidence
interval, 72-100), a 90% specificity (95% confidence interval, 81.7-93.8), an 88%
positive predictive value (95% confidence interval, 55.0-91.3), a 100% negative
predictive value (95% confidence interval, 90.9-100), a positive likelihood ratio
of 10.0 (95% confidence interval, 3.93-16.13), and a negative likelihood ratio of
0 (95% confidence interval, 0-0.34). Intrarater and interrater agreements were
94% (P < .001) and 93% (P < .001), respectively. CONCLUSION: The vascular index
accurately predicts the morbidly adherent placenta in patients with placenta
previa. In addition, 3-dimensional power Doppler vascular and vascular flow
indices were more predictive of severe cases of morbidly adherent placenta
compared with 2-dimensional ultrasound. This objective technique may limit the
variations in diagnosing morbidly adherent placenta because of the subjectivity
of 2-dimensional ultrasound interpretations.
PMID- 28400307
TI - Reply.
PMID- 28400308
TI - Racial and ethnic differences in the prevalence of metabolic syndrome and its
components of metabolic syndrome in women with polycystic ovary syndrome: a
regional cross-sectional study.
AB - BACKGROUND: Polycystic ovary syndrome is a heterogeneous disorder and its
presentation varies with race and ethnicity. Reproductive-age women with
polycystic ovary syndrome are at increased risk of metabolic syndrome; however,
it is not clear if prevalence of metabolic syndrome and clustering of its
components differs based on race and ethnicity. Moreover, the majority of these
women do not undergo routine screening for metabolic syndrome. OBJECTIVE: We
sought to compare the prevalence of metabolic syndrome and clustering of its
components in women with polycystic ovary syndrome in the United States with
women in India, Brazil, Finland, and Norway. STUDY DESIGN: This is a cross
sectional study performed in 1089 women with polycystic ovary syndrome from 1999
through 2016 in 5 outpatient clinics in the United States, India, Brazil,
Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam
criteria. Main outcome measures were: metabolic syndrome prevalence, blood
pressure, body mass index, fasting high-density lipoprotein cholesterol, fasting
triglycerides, and fasting glucose. Data from all sites were reevaluated for
appropriate application of diagnostic criteria for polycystic ovary syndrome,
identification of polycystic ovary syndrome phenotype, and complete metabolic
workup. The US White women with polycystic ovary syndrome were used as the
referent group. Logistic regression models were used to evaluate associations
between race and metabolic syndrome prevalence and its components and to adjust
for potential confounders, including age and body mass index. RESULTS: The median
age of the entire cohort was 28 years. Women from India had the highest mean
Ferriman-Gallwey score for clinical hyperandrogenism (15.6 +/- 6.5, P < .001).
The age-adjusted odds ratio for metabolic syndrome was highest in US Black women
at 4.52 (95% confidence interval, 2.46-8.35) compared with US White women. When
adjusted for age and body mass index, the prevalence was similar in the 2 groups.
Significantly more Black women met body mass index and blood pressure criteria (P
< .001), and fewer met fasting triglycerides criteria (P < .05). The age- and
body mass index-adjusted prevalence of metabolic syndrome was highest in Indian
women (odds ratio, 6.53; 95% confidence interval, 3.47-12.30) with abnormalities
in glucose and fasting high-density lipoprotein cholesterol criterion and in
Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17-3.98) with
abnormalities in blood pressure, glucose, and fasting high-density lipoprotein
cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence
of metabolic syndrome and its components compared to US White women. CONCLUSION:
Despite a unifying diagnosis of polycystic ovary syndrome, there are significant
differences in the prevalence of metabolic syndrome and clustering of its
components based on race and ethnicity, which may reflect contributions from both
racial and environmental factors. Our findings indicate the prevalence of
metabolic syndrome components varies in women with polycystic ovary syndrome,
such that compared to White women from the United States, Black US women had the
highest prevalence, whereas women from India and Norway had a higher prevalence
of metabolic syndrome independent of obesity. The differences in clustering of
components of metabolic syndrome based on ethnicity highlight the need to
routinely perform complete metabolic screening to identify specific targets for
cardiovascular risk reduction strategies in these reproductive-age women.
PMID- 28400309
TI - Marijuana and pregnancy: objective education is good, but biased education is
not.
PMID- 28400310
TI - Reply.
PMID- 28400312
TI - Assigning clinical codes with data-driven concept representation on Dutch
clinical free text.
AB - Clinical codes are used for public reporting purposes, are fundamental to
determining public financing for hospitals, and form the basis for reimbursement
claims to insurance providers. They are assigned to a patient stay to reflect the
diagnosis and performed procedures during that stay. This paper aims to enrich
algorithms for automated clinical coding by taking a data-driven approach and by
using unsupervised and semi-supervised techniques for the extraction of multi
word expressions that convey a generalisable medical meaning (referred to as
concepts). Several methods for extracting concepts from text are compared, two of
which are constructed from a large unannotated corpus of clinical free text. A
distributional semantic model (i.c. the word2vec skip-gram model) is used to
generalize over concepts and retrieve relations between them. These methods are
validated on three sets of patient stay data, in the disease areas of urology,
cardiology, and gastroenterology. The datasets are in Dutch, which introduces a
limitation on available concept definitions from expert-based ontologies (e.g.
UMLS). The results show that when expert-based knowledge in ontologies is
unavailable, concepts derived from raw clinical texts are a reliable alternative.
Both concepts derived from raw clinical texts perform and concepts derived from
expert-created dictionaries outperform a bag-of-words approach in clinical code
assignment. Adding features based on tokens that appear in a semantically similar
context has a positive influence for predicting diagnostic codes. Furthermore,
the experiments indicate that a distributional semantics model can find relations
between semantically related concepts in texts but also introduces erroneous and
redundant relations, which can undermine clinical coding performance.
PMID- 28400313
TI - The eMouveRecherche application competes with research devices to evaluate energy
expenditure, physical activity and still time in free-living conditions.
AB - The proliferation of smartphones is creating new opportunities to monitor and
interact with human subjects in free-living conditions since smartphones are
familiar to large segments of the population and facilitate data collection,
transmission and analysis. From accelerometry data collected by smartphones, the
present work aims to estimate time spent in different activity categories and the
energy expenditure in free-living conditions. Our research encompasses the
definition of an energy-saving function (PredEE) considering four physical
categories of activities (still, light, moderate and vigorous), their duration
and metabolic cost (MET). To create an efficient discrimination function, the
method consists of classifying accelerometry-transformed signals into categories
and of associating each category with corresponding Metabolic Equivalent Tasks.
The performance of the PredEE function was compared with two previously published
functions (f(eta,d)aedes,f(eta,d)nrjsi), and with two dedicated sensors
(Armband(r) and Actiheart(r)) in free-living conditions over a 12-h monitoring
period using 30 volunteers. Compared to the two previous functions, PredEE was
the only one able to provide estimations of time spent in each activity category.
In relative value, all the activity categories were evaluated similarly to those
given by Armband(r). Compared to Actiheart(r), the function underestimated still
activities by 10.1% and overestimated light- and moderate-intensity activities by
7.9% and 4.2%, respectively. The total energy expenditure error produced by
PredEE compared to Armband(r) was lower than those given by the two previous
functions (5.7% vs. 14.1% and 17.0%). PredEE provides the user with an accurate
physical activity feedback which should help self-monitoring in free-living
conditions.
PMID- 28400311
TI - Pregnancy, birth, and infant outcomes by maternal fertility status: the
Massachusetts Outcomes Study of Assisted Reproductive Technology.
AB - BACKGROUND: Births to subfertile women, with and without infertility treatment,
have been reported to have lower birthweights and shorter gestations, even when
limited to singletons. It is unknown whether these decrements are due to parental
characteristics or aspects of infertility treatment. OBJECTIVE: The objective of
the study was to evaluate the effect of maternal fertility status on the risk of
pregnancy, birth, and infant complications. STUDY DESIGN: All singleton live
births of >=22 weeks' gestation and >=350 g birthweight to Massachusetts resident
women in 2004-2010 were linked to hospital discharge and vital records. Women
were categorized by their fertility status as in vitro fertilization, subfertile,
or fertile. Women whose births linked to in vitro fertilization cycles from the
Society for Assisted Reproductive Technology Clinic Outcomes Reporting System
were classified as in vitro fertilization. Women with indicators of subfertility
but not treated with in vitro fertilization were classified as subfertile. Women
without indicators of subfertility or in vitro fertilization treatment were
classified as fertile. Risks of 15 adverse outcomes (gestational diabetes,
pregnancy hypertension, antenatal bleeding, placental complications [placenta
abruptio and placenta previa], prenatal hospitalizations, primary cesarean
delivery, very low birthweight [<1500 g], low birthweight [<2500 g], small-for
gestation birthweight [z-score <=-1.28], large-for-gestation birthweight [z-score
>=1.28], very preterm [<32 weeks], preterm [<37 weeks], birth defects, neonatal
death [0-27 days], and infant death [0-364 days of life]) were modeled by
fertility status with the fertile group as reference and the subfertile group as
reference, using multivariate log binomial regression and reported as adjusted
risk ratios and 95% confidence intervals. RESULTS: The study population included
459,623 women (441,420 fertile, 8054 subfertile, and 10,149 in vitro
fertilization). Women in the subfertile and in vitro fertilization groups were
older than their fertile counterparts. Risks for 6 of 6 pregnancy outcomes and 6
of 9 infant outcomes were increased for the subfertile group, and 5 of 6
pregnancy outcomes and 7 of 9 infant outcomes were increased for the in vitro
fertilization group. For 4 of the 6 pregnancy outcomes (uterine bleeding,
placental complications, prenatal hospitalizations, and primary cesarean) and 2
of the infant outcomes (low birthweight and preterm) the risk was greater in the
in vitro fertilization group, with nonoverlapping confidence intervals to the
subfertile group, indicating a substantially higher risk among in vitro
fertilization-treated women. The highest risks for the in vitro fertilization
women were uterine bleeding (adjusted risk ratio, 3.80; 95% confidence interval,
3.31-4.36) and placental complications (adjusted risk ratio, 2.81; 95% confidence
interval, 2.57-3.08), and for in vitro fertilization infants, very preterm birth
(adjusted risk ratio, 2.13; 95% confidence interval, 1.80-2.52), and very low
birthweight (adjusted risk ratio, 2.15; 95% confidence interval, 1.80-2.56). With
subfertile women as reference, risks for the in vitro fertilization group were
significantly increased for uterine bleeding, placental complications, prenatal
hospitalizations, primary cesarean delivery, low and very low birthweight, and
preterm and very preterm birth. CONCLUSION: These analyses indicate that,
compared with fertile women, subfertile and in vitro fertilization-treated women
tend to be older, have more preexisting chronic conditions, and are at higher
risk for adverse pregnancy outcomes, particularly uterine bleeding and placental
complications. The greater risk in in vitro fertilization-treated women may
reflect more severe infertility, more extensive underlying pathology, or other
unfavorable factors not measured in this study.
PMID- 28400314
TI - PEG-PE/clay composite carriers for doxorubicin: Effect of composite structure on
release, cell interaction and cytotoxicity.
AB - : A novel drug delivery system for doxorubicin (DOX), based on organic-inorganic
composites was developed. DOX was incorporated in micelles (M-DOX) of
polyethylene glycol-phosphatidylethanolamine (PEG-PE) which in turn were adsorbed
by the clay, montmorillonite (MMT). The nano-structures of the PEG-PE/MMT
composites of LOW and HIGH polymer loadings were characterized by XRD, TGA, FTIR,
size (DLS) and zeta measurements. These measurements suggest that for the LOW
composite a single layer of polymer intercalates in the clay platelets and the
polymer only partially covers the external surface, while for the HIGH composite
two layers of polymer intercalate and a bilayer may form on the external surface.
These nanostructures have a direct effect on formulation stability and on the
rate of DOX release. The release rate was reversely correlated with the degree of
DOX interaction with the clay and followed the sequence: M-DOX>HIGH
formulation>LOW formulation>DOX/MMT. Despite the slower release from the HIGH
formulation, its cytotoxicity effect on sensitive cells was as high as the "free"
DOX. Surprisingly, the LOW formulation, with the slowest release, demonstrated
the highest cytotoxicity in the case of Adriamycin (ADR) resistant cells.
Confocal microscopy images and association tests provided an insight into the
contribution of formulation-cell interactions vs. the contribution of DOX release
rate. Internalization of the formulations was suggested as a mechanism that
increases DOX efficiency, particularly in the ADR resistant cell line. The
employment of organic-inorganic hybrid materials as drug delivery systems, has
not reached its full potential, however, its functionality as an efficient
tunable release system was demonstrated. STATEMENT OF SIGNIFICANCE: DOX PEG
PE/clay formulations were design as an efficient drug delivery system. The main
aim was to develop PEG-PE/clay formulations of different structures based on
various PEG-PE/clay ratios in order to achieve tunable release rates, to control
the external surface characteristics and formulation stability. The formulations
showed significantly higher toxicity in comparison to "free" DOX, explained by
formulation internalization. For each cell line tested, sensitive and ADR
resistant, a different formulation structure was found most efficient. The
potential of PEG-PE/clay-DOX formulations to improve DOX administration efficacy
was demonstrated and should be further explored and implemented for other cancer
drugs and cells.
PMID- 28400315
TI - Permanent His-bundle pacing for cardiac resynchronization therapy: Initial
feasibility study in lieu of left ventricular lead.
AB - BACKGROUND: Permanent His-bundle pacing (HBP) has the potential to
physiologically normalize wide QRS duration in patients with bundle branch block
and cardiomyopathy. OBJECTIVE: The purpose of this study was to assess the
feasibility of incorporating a His-bundle lead for cardiac resynchronization
therapy (CRT) in lieu of a coronary sinus lead. METHODS: Patients with an
indication for CRT (n = 21) underwent attempted implantation of an HBP placed
into the left ventricular (LV) lead port. Intracardiac intervals, QRS duration,
New York Heart Association functional class, ejection fraction (EF),
echocardiography, and lead characteristics were measured at baseline and at
follow-up. RESULTS: Of the 21 patients in whom implantation was attempted, HBP
was successfully implanted in 16 (age 62 +/- 18 years, 4 females, EF 25 +/- 8). A
significant reduction in mean QRS was observed, with narrowing from 180 +/- 23 ms
to 129 +/- 13 ms (P <.0001). During the follow-up period, median New York Heart
Association functional class improved from III to II (P <.001), and mean LV EF
and left ventricular internal dimension in diastole (LVIDd) improved from 27% +/-
10% to 41% +/- 13% (P <.001) and from 5.4 +/- 0.4 cm to 4.5 +/- 0.3 cm (P <.001),
respectively. At median 12-month follow-up, no dislodgments were observed, and
only one patient lost nonselective capture that resolved with increased pacing
output. CONCLUSION: Permanent HBP is feasible for patients with an indication for
CRT using the LV port in lieu of a coronary sinus lead. In this initial
experience, narrowing of QRS duration was achieved in 76% of patients with bundle
branch block, and improvements in clinical and echocardiographic measures were
observed with HBP. Future prospective comparative studies with HBP to achieve CRT
are justifiable.
PMID- 28400316
TI - Glucose ingestion causes cardiac repolarization disturbances in type 1 long QT
syndrome patients and healthy subjects.
AB - BACKGROUND: Both hypoglycemia and severe hyperglycemia constitute known risk
factors for cardiac repolarization changes potentially leading to malignant
arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized
by long QT syndrome (LQTS) and may be at increased risk for glucose-induced
repolarization disturbances. OBJECTIVE: The purpose of this study was to test the
hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac
repolarization changes during the relative hyperglycemia that occurs after an
oral glucose load. METHODS: Fourteen KCNQ1 LQTS patients and 28 control
participants matched for gender, body mass index, and age underwent a 3-hour oral
75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia
corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the
Morphology Combination Score (MCS) were calculated. RESULTS: QTc and MCS
increased in both groups. MCS remained elevated until 150 minutes after glucose
ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS
patients compared with control subjects (0.28 +/- 0.27 vs 0.15 +/- 0.13; P <.05).
CONCLUSION: Relative hyperglycemia induced by ingestion of 75-g glucose caused
cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients
compared with control subjects.
PMID- 28400317
TI - The Long Winding Road to Transplant: How Sarcopenia and Debility Impact Morbidity
and Mortality on the Waitlist.
AB - Frailty and sarcopenia are common complications of cirrhosis. Frailty has been
described as an increased susceptibility to stressors secondary to a cumulative
decline in physiologic reserve; this decline occurs with aging or is a result of
the disease process, across multiple organ systems. Sarcopenia, a key component
of frailty, is defined as progressive and generalized loss of skeletal muscle
mass and strength. The presence of either of these complications is associated
with increased morbidity and mortality, as these are tightly linked to
decompensation and increased complication rates. Recognition of these entities is
critical. Studies have shown improvement in muscle strength and function lead to
reduced mortality, suggesting both frailty and sarcopenia are modifiable risk
factors. In this review we outline the prevalence of frailty and sarcopenia in
cirrhosis and the impact on clinical outcomes such as decompensation,
hospitalization, and mortality. Existing and potential novel therapeutic
approaches for frailty and sarcopenia are also reviewed.
PMID- 28400319
TI - Association of surgical excision and brachytherapy for the management of keloids.
AB - Many techniques have been described to prevent the appearance and relapse of
keloids but most of them have an efficacy lower than 50%. Our objective is to
describe our standardized management of keloids by associated surgery and
brachytherapy. Surgery-brachytherapy is usually given only when less invasive
treatments failed. Both a surgeon and a radiotherapist are involved. Forty-eight
hours of hospitalization in a surgery unit are required. The extra-lesional
excision is performed and a brachytherapy sheath is placed in the dermis plane.
An iridium source with an initial activity of 300 GBq is used to deliver high
dose rate brachytherapy. The brachytherapy sessions are held in a lead-shielded
room in a radiotherapy unit: the first session at 6 h after surgical excision,
while the second and third on the following day. The total dose administered is
18 Gy. A surgical workup is scheduled at 10 days. The patient is followed-up
closely by the radiotherapist for an 18-month period. The recurrence rate after 2
years is 8 to 12%. The main complaints are dyschromia, telangiectasia and skin
atrophy.
PMID- 28400318
TI - Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative
stress.
AB - Heart failure is a leading cause of morbidity and mortality in patients affected
by different disorders associated to intravascular hemolysis. The leading factor
is the presence of pathologic amount of pro-oxidant free heme in the bloodstream,
due to the exhaustion of the natural heme scavenger Hemopexin (Hx). Here, we
evaluated whether free heme directly affects cardiac function, and tested the
therapeutic potential of replenishing serum Hx for increasing serum heme
buffering capacity. The effect of heme on cardiac function was assessed in vitro,
on primary cardiomyocytes and H9c2 myoblast cell line, and in vivo, in Hx-/- mice
and in genetic and acquired mouse models of intravascular hemolysis. Purified Hx
or anti-oxidants N-Acetyl-L-cysteine and alpha-tocopherol were used to counteract
heme cardiotoxicity. In mice, Hx loss/depletion resulted in heme accumulation and
enhanced reactive oxygen species (ROS) production in the heart, which ultimately
led to severe systolic dysfunction. Similarly, high ROS reduced systolic Ca2+
transient amplitudes and fractional shortening in primary cardiomyocytes exposed
to free heme. In keeping with these Ca2+ handling alterations, oxidation and
CaMKII-dependent phosphorylation of Ryanodine Receptor 2 were higher in Hx-/-
hearts than in controls. Administration of anti-oxidants prevented systolic
failure both in vitro and in vivo. Intriguingly, Hx rescued contraction defects
of heme-treated cardiomyocytes and preserved cardiac function in hemolytic mice.
We show that heme-mediated oxidative stress perturbs cardiac Ca2+ homeostasis and
promotes contractile dysfunction. Scavenging heme, Hx counteracts cardiac heme
toxicity and preserves left ventricular function. Our data generate the rationale
to consider the therapeutic use of Hx to limit the cardiotoxicity of free heme in
hemolytic disorders.
PMID- 28400320
TI - Classification proposed of malignant intraosseous odontogenic tumors (MIOT).
AB - Malignant intraosseous odontogenic tumors (MIOT) of the jaws are very rare. The
diagnosis is difficult. Clinical, paraclinical and histological diagnostic
criteria, strict are well established. But the International Union Against Cancer
(UICC) does not provide TNM classification that will allow harmonization of the
treatment. Indeed, despite their location, they cannot be classified as primary
tumors of the oral cavity because of their localization in the bone marrow,
making them systematically classified as T4. We propose a classification taking
into account the clinical and radiological data.
PMID- 28400321
TI - Whither the chain of survival?
PMID- 28400322
TI - Bladder Involvement in Stage I Endometriosis.
AB - BACKGROUND: Endometriosis-the ectopic implantation of endometrial-like tissue
affects 10% of adolescent females and adults. Bladder involvement, causing
dysuria and hematuria, occurs in a very small number of endometriosis patients.
CASE: The patient presented at age 12 years with dysuria and pelvic pain.
Laparoscopy revealed stage I endometriosis. Postoperatively, she reported
persistent dysuria and passage of tissue in her urine. Cystoscopy showed diffuse
erythema; urine cytology revealed glandular and spindle cells suggestive of
endometriosis. She was transitioned from oral contraceptives to an intranasal
gonadotropin-releasing hormone agonist, with symptom resolution. SUMMARY AND
CONCLUSION: Intravesicular endometriosis coinciding with stage I disease supports
a mechanism of endometriosis dissemination other than direct bladder
infiltration. Patients with endometriosis who complain of urinary symptoms
warrant assessment, because intravesicular bladder involvement cannot be excluded
using pelviscopy.
PMID- 28400323
TI - Arabidopsis Transcription Factors SPL1 and SPL12 Confer Plant Thermotolerance at
Reproductive Stage.
AB - Plant reproductive organs are vulnerable to heat, but regulation of heat-shock
responses in inflorescence is largely uncharacterized. Here, we report that two
of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcriptional factors in
Arabidopsis, SPL1 and SPL12, act redundantly in thermotolerance at the
reproductive stage. The spl1-1 spl12-1 inflorescences displayed hypersensitivity
to heat stress, whereas overexpression of SPL1 or SPL12 enhanced the
thermotolerance in both Arabidopsis and tobacco. RNA sequencing revealed 1939
upregulated and 1479 downregulated genes in wild-type inflorescence upon heat
stress, among which one-quarter (1,040) was misregulated in spl1-1 spl12-1,
indicating that SPL1 and SPL12 contribute greatly to the heat-triggered
transcriptional reprogramming in inflorescence. Notably, heat stress induced a
large number of abscisic acid (ABA) responsive genes, of which ~39% were
disturbed in heat induction in spl1-1 spl12-1 inflorescence. Preapplication of
ABA and overexpression of SPL1 restored the inflorescence thermotolerance in spl1
1 spl12-1 and in the ABA biosynthesis mutant aba2-1, but not in the pyl sextuple
mutant defective in ABA receptors PYR1/PYL1/PYL2/PYL4/PYL5/PYL8. Thus,
inflorescence thermotolerance conferred by SPL1 and SPL2 involves PYL-mediated
ABA signaling. The molecular network consisting of SPL1 and SPL12 illustrated
here shed new light on the mechanisms of plant thermotolerance at the
reproductive stage.
PMID- 28400324
TI - Impact of anatase titanium dioxide nanoparticles on mutagenic and genotoxic
response in Chinese hamster lung fibroblast cells (V-79): The role of cellular
uptake.
AB - The unique physico-chemical properties of nano crystalline anatase titanium
dioxide nanoparticles (TiO2 NPs) render them with different biological and
chemical activities. Hence, it is widely used in industrial and consumer
applications. Previous studies have shown the genotoxicity of TiO2 NPs. However,
there is a paucity of data regarding mutagenicity of these NPs. In the present
study, the cellular uptake, sub-cellular localization, cytotoxicity and short
term DNA interaction of TiO2 NPs (1-100 MUgmL-1) of diameter ranging from 12 to
25 nm on mammalian lung fibroblast cells (V-79) has been studied. The flow
cytometric analysis and electron micrographs of V-79 monolayer showed the
internalization of TiO2 NPs in the cytoplasm with the confirmation of elemental
composition through SEM/EDX analysis. TEM analysis also showed TiO2 NPs induced
ultra-structural changes such as swollen mitochondria and nuclear membrane
disruption in V-79 cells. TiO2 NPs generated free radicals, which induced
indirect mutagenic and genotoxic responses. Apart from measuring the genotoxicity
by Comet assay, the mutagenic potential of TiO2 NPs in V-79 cells was evaluated
by mammalian HGPRT gene forward mutation assay, showing a 2.98- fold increase in
6TGR HGPRT mutant frequency (*p < 0.05, **p < 0.01, ***p < 0.001) by culture
plate method, which is an early indicator of potential carcinogenicity. Hence,
TiO2 NPs should be closely monitored and there should be a judicious use and
disposal of NPs.
PMID- 28400325
TI - Juncaceae species as sources of innovative bioactive compounds for the food
industry: In vitro antioxidant activity, neuroprotective properties and in silico
studies.
AB - Several Juncus species are traditionally used as sedative and to treat health
problems like insomnia. This work was based on the hypothesis that Juncus acutus,
J. maritimus and J. inflexus may have molecules with bioactivities relevant for
the improvement of cognitive functions and thus with potential use as food
additives and/or nutraceuticals. Therefore leaves and roots extracts of those
species were evaluated for radical scavenging (RSA) and metal chelating
activities, and for in vitro inhibition of acetyl-(AChE) and
butyrylcholinesterase (BuChE). The bioactive compound was isolated and identified
by HPLC-DAD, and its anticholinesterase capacity was determined by different
assays. Docking studies were performed to elucidate its inhibitory mechanism. The
dichloromethane root extract of J. acutus had the highest RSA against DPPH and
ABTS radicals, and the dichloromethane extract of J. maritimus leaves had the
uppermost FRAP. The dichloromethane extract from J. acutus leaves had the
strongest BuChE inhibition. Juncunol was the bioactive compound, exhibiting dual
anticholinesterase capacity on enzyme-based assays and AChE inhibition in
neuronal and glial cells in vitro. Molecular docking studies indicate juncunol as
a competitive reversible inhibitor. Our results suggest that Juncus spp. can be
sources of bioactive compounds with application in the food industry as cognitive
enhancer nutraceuticals.
PMID- 28400326
TI - Developmental visual perception deficits with no indications of prosopagnosia in
a child with abnormal eye movements.
AB - Visual categories are associated with eccentricity biases in high-order visual
cortex: Faces and reading with foveally-biased regions, while common objects and
space with mid- and peripherally-biased regions. As face perception and reading
are among the most challenging human visual skills, and are often regarded as the
peak achievements of a distributed neural network supporting common objects
perception, it is unclear why objects, which also rely on foveal vision to be
processed, are associated with mid-peripheral rather than with a foveal bias.
Here, we studied BN, a 9 y.o. boy who has normal basic-level vision, abnormal
(limited) oculomotor pursuit and saccades, and shows developmental object and
contour integration deficits but with no indication of prosopagnosia. Although we
cannot infer causation from the data presented here, we suggest that normal
pursuit and saccades could be critical for the development of contour integration
and object perception. While faces and perhaps reading, when fixated upon, take
up a small portion of central visual field and require only small eye movements
to be properly processed, common objects typically prevail in mid-peripheral
visual field and rely on longer-distance voluntary eye movements as saccades to
be brought to fixation. While retinal information feeds into early visual cortex
in an eccentricity orderly manner, we hypothesize that propagation of non-foveal
information to mid and high-order visual cortex critically relies on circuitry
involving eye movements. Limited or atypical eye movements, as in the case of BN,
may hinder normal information flow to mid-eccentricity biased high-order visual
cortex, adversely affecting its development and consequently inducing visual
perceptual deficits predominantly for categories associated with these regions.
PMID- 28400327
TI - A multisensory perspective on object memory.
AB - Traditional studies of memory and object recognition involved objects presented
within a single sensory modality (i.e., purely visual or purely auditory
objects). However, in naturalistic settings, objects are often evaluated and
processed in a multisensory manner. This begets the question of how object
representations that combine information from the different senses are created
and utilised by memory functions. Here we review research that has demonstrated
that a single multisensory exposure can influence memory for both visual and
auditory objects. In an old/new object discrimination task, objects that were
presented initially with a task-irrelevant stimulus in another sense were better
remembered compared to stimuli presented alone, most notably when the two stimuli
were semantically congruent. The brain discriminates between these two types of
object representations within the first 100ms post-stimulus onset, indicating
early "tagging" of objects/events by the brain based on the nature of their
initial presentation context. Interestingly, the specific brain networks
supporting the improved object recognition vary based on a variety of factors,
including the effectiveness of the initial multisensory presentation and the
sense that is task-relevant. We specify the requisite conditions for multisensory
contexts to improve object discrimination following single exposures, and the
individual differences that exist with respect to these improvements. Our results
shed light onto how memory operates on the multisensory nature of object
representations as well as how the brain stores and retrieves memories of
objects.
PMID- 28400329
TI - Deletion of Type I glutamine synthetase deregulates nitrogen metabolism and
increases ethanol production in Clostridium thermocellum.
AB - Clostridium thermocellum rapidly deconstructs cellulose and ferments resulting
hydrolysis products into ethanol and other products, and is thus a promising
platform organism for the development of cellulosic biofuel production via
consolidated bioprocessing. While recent metabolic engineering strategies have
targeted eliminating canonical fermentation products (acetate, lactate, formate,
and H2), C. thermocellum also secretes amino acids, which has limited ethanol
yields in engineered strains to approximately 70% of the theoretical maximum. To
investigate approaches to decrease amino acid secretion, we attempted to reduce
ammonium assimilation by deleting the Type I glutamine synthetase (glnA) in an
essentially wild type strain of C. thermocellum. Deletion of glnA reduced levels
of secreted valine and total amino acids by 53% and 44% respectively, and
increased ethanol yields by 53%. RNA-seq analysis revealed that genes encoding
the RNF-complex were more highly expressed in DeltaglnA and may have a role in
improving NADH-availability for ethanol production. While a significant up
regulation of genes involved in nitrogen assimilation and urea uptake suggested
that deletion of glnA induces a nitrogen starvation response, metabolomic
analysis showed an increase in intracellular glutamine levels indicative of
nitrogen-rich conditions. We propose that deletion of glnA causes deregulation of
nitrogen metabolism, leading to overexpression of nitrogen metabolism genes and,
in turn, elevated glutamine levels. Here we demonstrate that perturbation of
nitrogen assimilation is a promising strategy to redirect flux from the
production of nitrogenous compounds toward biofuels in C. thermocellum.
PMID- 28400328
TI - You talkin' to me? Communicative talker gaze activates left-lateralized superior
temporal cortex during perception of degraded speech.
AB - Neuroimaging studies of speech perception have consistently indicated a left
hemisphere dominance in the temporal lobes' responses to intelligible auditory
speech signals (McGettigan and Scott, 2012). However, there are important
communicative cues that cannot be extracted from auditory signals alone,
including the direction of the talker's gaze. Previous work has implicated the
superior temporal cortices in processing gaze direction, with evidence for
predominantly right-lateralized responses (Carlin & Calder, 2013). The aim of the
current study was to investigate whether the lateralization of responses to
talker gaze differs in an auditory communicative context. Participants in a
functional MRI experiment watched and listened to videos of spoken sentences in
which the auditory intelligibility and talker gaze direction were manipulated
factorially. We observed a left-dominant temporal lobe sensitivity to the
talker's gaze direction, in which the left anterior superior temporal
sulcus/gyrus and temporal pole showed an enhanced response to direct gaze -
further investigation revealed that this pattern of lateralization was modulated
by auditory intelligibility. Our results suggest flexibility in the distribution
of neural responses to social cues in the face within the context of a
challenging speech perception task.
PMID- 28400330
TI - Metabolomics-driven approach to solving a CoA imbalance for improved 1-butanol
production in Escherichia coli.
AB - High titer 1-butanol production in Escherichia coli has previously been achieved
by overexpression of a modified clostridial 1-butanol production pathway and
subsequent deletion of native fermentation pathways. This strategy couples growth
with production as 1-butanol pathway offers the only available terminal electron
acceptors required for growth in anaerobic conditions. With further inclusion of
other well-established metabolic engineering principles, a titer of 15g/L has
been obtained. In achieving this titer, many currently existing strategies have
been exhausted, and 1-butanol toxicity level has been surpassed. Therefore,
continued engineering of the host strain for increased production requires
implementation of alternative strategies that seek to identify non-obvious
targets for improvement. In this study, a metabolomics-driven approach was used
to reveal a CoA imbalance resulting from a pta deletion that caused undesirable
accumulation of pyruvate, butanoate, and other CoA-derived compounds. Using
metabolomics, the reduction of butanoyl-CoA to butanal catalyzed by alcohol
dehydrogenase AdhE2 was determined as a rate-limiting step. Fine-tuning of this
activity and subsequent release of free CoA restored the CoA balance that
resulted in a titer of 18.3g/L upon improvement of total free CoA levels using
cysteine supplementation. By enhancing AdhE2 activity, carbon flux was directed
towards 1-butanol production and undesirable accumulation of pyruvate and
butanoate was diminished. This study represents the initial report describing the
improvement of 1-butanol production in E. coli by resolving CoA imbalance, which
was based on metabolome analysis and rational metabolic engineering strategies.
PMID- 28400331
TI - Four paralog gelsolin genes are differentially expressed in the earthworm
Lumbricus terrestris.
AB - We have identified and characterized four distinct variants of the gelsolin
related protein (EWAM P1-P4) in the earthworm L. terrestris. All of these
proteins biochemically qualify as gelsolins since they sever actin filaments in a
calcium dependent manner. P1, P2 and P3 are present in the Lumbricus body wall
muscle whereas in the gizzard muscle P3 and P4 were found. P1-P4 are encoded by
four paralog genes and are differentially expressed in various muscle cell
tissues. While the genes for P1 and P2 contain one intron, there was no intron in
both P3 and P4 genes. The coding sequences consist of 1104bp (368 amino acids)
for P1/P4 and 1101bp (367 amino acids) for P2/P3. Corresponding genes were
confirmed by northern blot analysis which revealed three (calculated lengths:
3100, 2300 and 2100 nucleotides) and two (calculated lengths: 2300 and 1700
nucleotides) mRNA transcripts in the body wall and the gizzard, respectively.
EWAM mRNA was localized by fluorescence in situ hybridization in the body wall
and the gizzard muscle. P1 mRNA was detected in the inner proximal layers of both
the circular and longitudinal muscle of the body wall whereas in the gizzard no
significant staining was observed for P1. P2-P4 mRNAs were abundant in the outer
distal layers of both the circular and the longitudinal muscles of both body wall
and gizzard. The differential expression of four paralog gelsolin genes suggests
a functional adaptation of different muscle cells with respect to actin filament
turnover and modulation of its polymer state.
PMID- 28400332
TI - Sexual dimorphic expression of dnd in germ cells during sex reversal and its
requirement for primordial germ cell survival in protogynous hermaphroditic
grouper.
AB - Dead end (dnd), vertebrate-specific germ cell marker, had been demonstrated to be
essential for primordial germ cell (PGC) migration and survival, and the link
between PGC number and sex change had been revealed in some teleost species, but
little is known about dnd in hermaphroditic vertebrates. In the present study, a
protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides) dnd
homologue (Ecdnd) was identified and characterized. Quantitative real-time PCR
and in situ hybridization analysis revealed a dynamic and sexually dimorphic
expression pattern in PGCs and germ cells of gonads. During sex changing, the
Ecdnd transcript sharply increased in early transitional gonad, reached the
highest level at late transitional gonad stage, and decreased after testis
maturation. Visualization of zebrafish PGCs by injecting with RFP-Ecdnd-3'UTR RNA
and GFP-zfnanos3-3'UTR RNA confirmed importance of Ecdnd 3'UTR for the PGC
distribution. In addition, knockdown of EcDnd by using antisense morpholinos (MO)
caused the ablation of PGCs in orange-spotted grouper. Therefore, the current
data indicate that Ecdnd is essential for PGCs survival and may serve as a useful
germ cell marker during gametogenesis in hermaphroditic grouper.
PMID- 28400333
TI - Umbilical cord mesenchymal stem cells are able to undergo differentiation into
functional islet-like cells in type 2 diabetic tree shrews.
AB - Islet transplantation is arguably one of the most promising strategies to treat
patients suffering with diabetes mellitus. However, a combination of a lack of
donors and chronic immune rejection limit clinical applications. Here, we
evaluated the efficacy of cell therapy using islet-like cells differentiated from
umbilical cord mesenchymal stem cells (UC-MSCs) of tree shrews for the treatment
of type 2 diabetes. Enhanced green fluorescent protein (eGFP) labeled UC-MSCs
were directly injected into type 2 diabetic tree shrews, where UC-MSC
differentiated into functional islet-like cells and alleviated disease severity,
as evidenced by improved biochemical features and reduced concentrations of
inflammatory cytokines. We also demonstrated that in vitro culture of UC-MSCs for
six days in a high-glucose environment (40 mmol/L or 60 mmol/L glucose) resulted
in significant gene methylation. The potency of UC-MSCs differentiated into
insulin-secreting cells was attributed to the activation of Notch signal
pathways. This study provides evidence that cell therapy of islet-like cells
differentiated from UC-MSCs is a feasible, simple and inexpensive approach in the
treatment of type 2 diabetes.
PMID- 28400334
TI - Asporin promotes pancreatic cancer cell invasion and migration by regulating the
epithelial-to-mesenchymal transition (EMT) through both autocrine and paracrine
mechanisms.
AB - Pancreatic cancer is histopathologically characterized by excessive desmoplasia
induced by pancreatic stellate cells (PSCs). Asporin, an extracellular matrix
(ECM) protein, is highly expressed in cancer-associated fibroblasts (CAFs).
Asporin expression in PSCs and its roles in PSC-pancreatic cancer cell (PCC)
interaction remain unclear. The present study firstly showed that Asporin is
highly expressed in activated PSCs and is involved in PSC-mediated invasion and
migration of PCCs. Exogenous Asporin interacted with the transmembrane receptor
CD44 on PCCs to activate NF-kappaB/p65 and promoted the epithelial-mesenchymal
transition (EMT) in PCCs. Furthermore, AKT and ERK pathways participated in
Asporin/CD44-induced NF-kappaB/p65 activation in pancreatic cancer. Asporin had
similar effects on PCCs via an autocrine mechanism. Consistent with our in vitro
experiments, we showed that Asporin in peritumoral stroma of pancreatic cancer
tissues was associated with poor clinical outcome. In conclusion, this is the
first study to show that Asporin promotes EMT, invasion, and migration of PCCs by
activating CD44-AKT/ERK-NF-kappaB pathway in paracrine and autocrine manners.
Moreover, our results indicate that Asporin may be a prognostic marker and
suggest that targeting the tumor microenvironment represents a promising
therapeutic strategy in pancreatic cancer.
PMID- 28400335
TI - Review: Regulation of the cancer epigenome by long non-coding RNAs.
AB - Long non-coding RNAs have emerged as highly versatile players in the regulation
of gene expression in development and human disease, particularly cancer.
Hundreds of lncRNAs become dysregulated across tumor types, and multiple lncRNAs
have demonstrated functions as tumor-suppressors or oncogenes. Furthermore,
studies have demonstrated that dysregulation of lncRNAs results in alterations of
the epigenome in cancer cells, potentially providing a novel mechanism for the
massive epigenomic alterations observed in many tumors. Here, we highlight and
provide some illustrious examples of lncRNAs in various epigenetic regulatory
processes, including coordination of chromatin dynamics, regulation of DNA
methylation, modulation of other non-coding RNAs and mRNA stability, and control
of epigenetic substrate availability through altered tumor metabolism. In light
of all these known and emerging functions in epigenetic regulation of
tumorigenesis and cancer progression, lncRNAs represent attractive targets for
future therapeutic strategies in cancer.
PMID- 28400337
TI - Editorial - Special issue on Fighting Pancreatic Cancer.
PMID- 28400336
TI - ASPP2 suppresses invasion and TGF-beta1-induced epithelial-mesenchymal transition
by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric
cancer.
AB - ASPP2 regulates cell polarity and cell-cell adhesion by binding to, and co
localizing with PAR3 at tight junctions. Here we show a novel role of ASPP2 in
suppressing gastric cancer (GC) invasiveness. Immunoprecipitation and
immunofluorescence analyses showed that ASPP2 promoted the recruitment of PAR3 to
cell-cell junctions in GC cells. Diminished expression of ASPP2 and loss of
junctional PAR3 localization were significantly associated with diffuse-type
histology, deeper invasion depth, positive peritoneal dissemination and worse
prognosis in primary GC. ASPP2 suppressed migration and invasion of GC cells in
vitro and peritoneal dissemination of GC cells in vivo in a mouse model. ASPP2
suppressed epithelial-mesenchymal transition (EMT) induced by TGF-beta1-Smad2/3
signaling in GC cells through suppression of the degradation of Smad7, a negative
regulator of TGF-beta1-Smad2/3 signaling, by interacting with the E3 ubiquitin
ligase ITCH. In conclusion, ASPP2 suppresses invasion, peritoneal dissemination
and TGF-beta1-induced EMT by inhibiting Smad7 degradation mediated by ITCH.
PMID- 28400338
TI - Recommendations for aerosolized antibiotics in ventilator-associated pneumonia
and ventilator-associated tracheobronchitis: too little and too late?
PMID- 28400339
TI - Albendazole-responsive disseminated Tubulinosema acridophagus in a patient with
chronic lymphocytic leukaemia.
PMID- 28400340
TI - Eosin fluorescence: A diagnostic tool for quantification of liver injury.
AB - Hepatitis is one of the most common life threatening diseases. The diagnosis is
mainly based on biochemical analysis such as liver function test. However,
histopathological evaluation of liver serves far better for more accurate final
diagnosis. The goal of our study was to evaluate the eosin fluorescence pattern
in CCl4-induced liver injury model compared with normal and different treatment
groups. For this purpose, liver tissues were stained with H/E and examined under
bright field microscope but the fluorescence microscopy of H/E stained slides
provided an interesting fluorescence pattern and was quite helpful in identifying
different structures. Interesting fluorescence patterns were obtained with FITC,
Texas Red and Dual channel filter cubes that were quite helpful in identifying
different morphological features of the liver. During the course of hepatic
injury, liver cells undergo necrosis, apoptosis and overall cellular
microenvironment is altered due to the modification of proteins and other
intracellular molecules. Intensified eosin fluorescence was observed around the
central vein of injured liver compared to normal indicating enhanced binding of
eosin to the more exposed amino acid residues. To conclude, eosin fluorescence
pattern varies with the health status of a tissue and can be used further for the
diagnosis and quantification of severity of various liver diseases.
PMID- 28400341
TI - Efficacy and safety of total glucosides of paeony combined with acitretin in the
treatment of moderate-to-severe plaque psoriasis: a double-blind, randomised,
placebo-controlled trial.
AB - Although acitretin has been widely used for the treatment of psoriasis,
additional safer and more effective approaches, including traditional Chinese
medicine, are needed. To investigate the efficacy and safety of total glucosides
of paeony (TGP) combined with acitretin in the treatment of moderate-to-severe
plaque psoriasis. A randomised, double-blind, placebo-controlled, multi-centre
clinical study was conducted. In total, 108 patients with moderate-to-severe
plaque psoriasis were randomly assigned to treatment with "TGP plus acitretin"
(group A) or "placebo plus acitretin" (group B) for 12 weeks. After 12 weeks of
therapy, the percentage of patients achieving a 50% reduction in Psoriasis Area
and Severity Index was 90% in group A and 70.5% in group B (p<0.05). The rate of
serum alanine aminotransferase elevation was 6.25% in group A and 20.4% in group
B (p<0.05). TGP is conducive to enhancing anti-psoriatic efficacy and reducing
liver damage due to acitretin. TGP combined with acitretin is a safe and
effective treatment approach for moderate-to-severe plaque psoriasis.
PMID- 28400342
TI - Editorial: What's new this month?
PMID- 28400344
TI - Clues in skin surgery: The chondrocutaneous helix rim advancement flap.
PMID- 28400343
TI - Dermpath & Clinic: A persistent scrotal rash.
PMID- 28400345
TI - sQUIZ your knowledge: A pinkish nodular lesion.
PMID- 28400346
TI - sQuiz your knowledge: Progressive loss of teeth and ulcerative genital lesions.
PMID- 28400347
TI - sQuiz your knowledge: Expanding scarring alopecia in a patient with porphyria
cutanea tarda.
PMID- 28400348
TI - To clip or not to clip the breast tumor bed? A retrospective look at the
geographic miss index and normal tissue index of 110 patients with breast cancer.
AB - OBJECTIVE: Planning of breast radiation for patients with breast conserving
surgery often relies on clinical markers such as scars. Lately, surgical clips
have been used to identify the tumor location. The purpose of this study was to
evaluate the geographic miss index (GMI) and the normal tissue index (NTI) for
the electron boost in breast cancer treatment plans with and without surgical
clips. MATERIAL AND METHODS: A retrospective descriptive study of 110 consecutive
post-surgical patients who underwent breast-conserving treatment in early breast
cancer, in which the clinical treatment field with the radiologic (clipped) field
were compared and GMI/NTI for the electron boost were calculated respectively.
RESULTS: The average clinical field was 100 mm (range, 100-120 mm) and the
clipped field was 90 mm (range, 80-100 mm). The average GMI was 11.3% (range, 0
44%), and the average NTI was 27.5% (range, 0-54%). The GMI and NTI were reduced
through the use of intra-surgically placed clips. CONCLUSION: The impact of local
tumor control on the survival of patients with breast cancer is also influenced
by the precision of radiotherapy. Additionally, patients demand an appealing
cosmetic result. This makes "clinical" markers such as scars unreliable for
radiotherapy planning. A simple way of identifying the tissue at risk is by intra
surgical clipping of the tumor bed. Our results show that the use of surgical
clips can reduce the diameter of the radiotherapy field and increase the accuracy
of radiotherapy planning. With the placement of surgical clips, more tissue at
risk is included in the radiotherapy field. Less normal tissue receives
radiotherapy with the use of surgical clips.
PMID- 28400349
TI - The level of using family planning methods and factors that influence the
preference of methods in the Konya-Meram area.
AB - OBJECTIVE: To determine the level of contraceptive method use and factors that
influence the preference of method among women of reproductive age that live in
Meram, the central district of Konya. MATERIAL AND METHODS: Parameters such as
age, duration of marriage, number of pregnancies and births, socioeconomic
status, education level, and preferred contraceptive method of women who
presented to the family planning outpatient clinic of our hospital over a five
year period between January 1st, 2010, and December 31st, 2015, were recorded and
evaluated. RESULTS: The mean age of the women was identified as 31.57+/-8.14
years, the mean duration of marriage was 10.3+/-8.14 years, the mean number of
births was 1.92+/-1.01, and the mean number of children was 1.83+/-0.90. Among
the women in the study group, 65% were high school graduates, 88.92% had social
security, and 82.84% were in the middle-income group according to their financial
status. Only 31 patients were not married officially. It was observed that the
most preferred method was intrauterine device (IUD), and the least preferred
method was subcutaneous implant (SI). The use of IUD, oral contraceptives, and SI
increased as the socioeconomic status and educational level improved (p<0.05).
CONCLUSION: To ensure that women of reproductive age use effective family
planning methods, the education levels and socioeconomic status of women must be
improved.
PMID- 28400350
TI - Extraperitoneal lymph node dissection in locally advanced cervical cancer; the
prognostic factors associated with survival.
AB - OBJECTIVE: Surgical staging was recently recommended for the decision of
treatment in locally advanced cervical cancer. We aimed to investigate clinical
outcomes as well as factors associated with overall survival (OS) in patients
with locally advanced cervical cancer who had undergone extraperitoneal lymph
node dissection and were managed according to their lymph node status. MATERIAL
AND METHODS: The medical records of 233 women with stage IIb-IVa cervical cancer
who were clinically staged and underwent extraperitoneal lymph node dissection
were retrospectively reviewed. Paraaortic lymph node status determined the
appropriate radiotherapeutic treatment field. Surgery-related complications and
clinical outcomes were evaluated. RESULTS: The median age of the patients was 52
years (range, 26-88 years) and the median follow-up time was 28.4 months (range,
3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node
dissection and 202 patients underwent laparotomy. The number of paraaortic lymph
nodes extracted was similar for both techniques. Sixty-two (27%) of the 233
patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates
were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic
paraaortic lymph nodes, tumor type, and paraaortic lymph node status were
associated with OS. In multivariate Cox regression analyses, tumor type, stage,
and presence of paraaortic lymph node metastases were the independent prognostic
factors of OS. CONCLUSION: Paraaortic lymph node metastasis is the most important
prognostic factor affecting survival. Surgery would give hints about the
prognosis and treatment planning of the patient.
PMID- 28400351
TI - Frequency of nodular goiter and autoimmune thyroid disease and association of
these disorders with insulin resistance in polycystic ovary syndrome.
AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in
women. Nodular goiter and autoimmune thyroid disease (AITD) are endocrinologic
abnormalities that have high prevalence. The purpose of our study was to detect
the prevalence of AITD and nodular goiter in patients with PCOS and investigate
whether PCOS-related hormones and metabolic factors affect these thyroid
disorders. MATERIAL AND METHODS: Ninety-seven women with PCOS and 71 healthy
female volunteers were recruited into the study. Serum-free thyroxine, thyroid
stimulating hormone, anti-thyroperoxidase antibody and anti-thyroglobulin
antibody levels were evaluated. Thyroid volume (TV) was calculated using
ultrasonography. RESULTS: The body mass index (BMI), Waist/Hip ratio, homeostasis
model assessment insulin resistance (HOMA-IR), fasting blood glucose,
triglyceride and low-density lipoproteins, and fasting insulin were significantly
higher in the PCOS group (p<.05). The control group had significantly higher
serum high density lipoprotein cholesterol results (p=.005). The mean TV was
11.4+/-4.7 mL in the PCOS group and 9.9+/-2.8 mL in the controls (p=.022). Twenty
nine patients with PCOS (29/97; 29.9%) had thyroid nodules, whereas only eleven
control subjects had thyroid nodules (11/71; 15.5%) (p=.043). The frequency of
AITD was significantly higher in the PCOS group (p=.001). A statistically
significant relationship was found between TV and age, fasting glucose, HOMA-IR,
BMI, and fasting insulin (p<.05). Participants with thyroid nodules were older
and had higher fasting glucose, BMI, fasting insulin, and HOMA-IR values compared
with those without thyroid nodules (p<.05). CONCLUSION: We demonstrated that TV
and frequency of nodular goiter were increased in patients with PCOS. This result
was related with insulin resistance. Therefore, we recommend that patients with
PCOS must be investigated for the development of nodular goiter and AITD.
PMID- 28400352
TI - Frequency of uterine sarcomas in patients admitted for uterine fibroid surgery.
AB - OBJECTIVE: To estimate the frequency of unsuspected uterine sarcoma identified
postoperatively in women undergoing surgery for presumed benign uterine fibroids
at a single university hospital. MATERIAL AND METHODS: This was a retrospective
single-center study; the records of all 2275 patients with uterine fibroids and
uterine sarcomas from 2003 to 2015 were reviewed. Descriptive statistics were
used to analyze demographic and clinical characteristics. To calculate confidence
intervals (CIs), the Clopper-Pearson Exact method was applied. RESULTS:
Preoperatively, 2269 patients had presumed benign uterine fibroids, and six
patients had suspected uterine sarcoma. Among the 2269 patients who underwent
surgery for presumed uterine fibroids, endometrial stromal sarcoma was
histopathologically revealed in only one patient [0.044%, 95% CI: (0.001-0.25)]
after laparoscopic subtotal hysterectomy with morcellation. All six patients who
were preoperatively diagnosed having uterine sarcoma underwent direct
conventional cancer treatment. Histopathologic analyses confirmed four cases of
uterine leiomyosarcoma, one high-grade undifferentiated uterine sarcoma, and one
embryonal rhabdomyosarcoma. Altogether, seven women were diagnosed as having
uterine sarcomas over this twelve-year period. CONCLUSION: In our institution,
the frequency of unsuspected uterine sarcomas was 1/2269 (0.044%) among women who
underwent myomectomies and hysterectomies to treat presumed benign uterine
fibroids.
PMID- 28400353
TI - Young People's Preferences for an Asthma Self-Management App Highlight
Psychological Needs: A Participatory Study.
AB - BACKGROUND: Although the prevalence of mental illness among young people with
asthma is known to be twice the rate of the wider population, none of the asthma
apps reported have acknowledged or attempted to include psychological support
features. This is perhaps because user involvement in the development of asthma
apps has been scarce. User involvement, facilitated by participatory design
methods, can begin to address these issues while contributing insights to our
understanding of the psychological experience associated with asthma and how
technology might improve quality of life. OBJECTIVE: The goal of this
participatory user research study was to explore the experience, needs, and ideas
of young people with asthma while allowing them to define requirements for an
asthma app that would be engaging and effective at improving their well-being.
METHODS: Young people aged 15-24 years with doctor-diagnosed asthma were invited
to participate in a participatory workshop and to complete a workbook designed to
elicit their thoughts and ideas about living with asthma, technology use, and the
design of an app. Participants generated a number of artifacts (including
collages, concept maps, and paper prototypes) designed to reify their ideas,
tacit knowledge, and experience. RESULTS: A total of 20 participants (mean age
17.8 years; 60%, 12/20 female) representing a range from inadequately to well
controlled asthma completed a workbook and 13 of these also took part in a
workshop (four workshops were held in total), resulting in 102 participant
generated artifacts. Theoretical thematic analysis resulted in a set of personal
needs, feature ideas, and app characteristics considered relevant by young people
for an asthma support app. The data revealed that psychological factors such as
anxiety, and impediments to autonomy, competence, and relatedness (as consistent
with self-determination theory [SDT]), were considered major influences on
quality of life by young people with asthma. Furthermore, the incorporation of
features pertaining to psychological experience was particularly valued by
participants. CONCLUSIONS: In addition to practical features for asthma
management, an app for young people with asthma should include support for the
mental health factors associated with lived experience (ie, anxiety, lack of
autonomy, and social disconnectedness). We show how support for these factors can
be translated into design features of an app for asthma. In addition to informing
the development of asthma-support technologies for young people, these findings
could have implications for technologies designed to support people with chronic
illness more generally.
PMID- 28400354
TI - Usability of a Novel Mobile Health iPad App by Vulnerable Populations.
AB - BACKGROUND: Recent advances in mobile technologies have created new opportunities
to reach broadly into populations that are vulnerable to health disparities.
However, mobile health (mHealth) strategies could paradoxically increase health
disparities, if low socioeconomic status individuals lack the technical or
literacy skills needed to navigate mHealth programs. OBJECTIVE: The aim of this
study was to determine whether patients from vulnerable populations could
successfully navigate and complete an mHealth patient decision aid. METHODS: We
analyzed usability data from a randomized controlled trial of an iPad program
designed to promote colorectal cancer (CRC) screening. The trial was conducted in
six primary care practices and enrolled 450 patients, aged 50-74 years, who were
due for CRC screening. The iPad program included a self-survey and randomly
displayed either a screening decision aid or a video about diet and exercise. We
measured participant ability to complete the program without assistance and
participant-rated program usability. RESULTS: Two-thirds of the participants
(305/450) were members of a vulnerable population (limited health literacy,
annual income < US $20,000, or black race). Over 92% (417/450) of the
participants rated the program highly on all three usability items (90.8% for
vulnerable participants vs 96.6% for nonvulnerable participants, P=.006). Only
6.9% (31/450) of the participants needed some assistance to complete the program.
In multivariable logistic regression, being a member of a vulnerable population
was not associated with needing assistance. Only older age, less use of text
messaging (short message service, SMS), and lack of Internet use predicted
needing assistance. CONCLUSIONS: Individuals who are vulnerable to health
disparities can successfully use well-designed mHealth programs. Future research
should investigate whether mHealth interventions can reduce health disparities.
PMID- 28400355
TI - Mobile Phone-Delivered Cognitive Behavioral Therapy for Insomnia: A Randomized
Waitlist Controlled Trial.
AB - BACKGROUND: This study is one of the first randomized controlled trials
investigating cognitive behavioral therapy for insomnia (CBT-I) delivered by a
fully automated mobile phone app. Such an app can potentially increase the
accessibility of insomnia treatment for the 10% of people who have insomnia.
OBJECTIVE: The objective of our study was to investigate the efficacy of CBT-I
delivered via the Sleepcare mobile phone app, compared with a waitlist control
group, in a randomized controlled trial. METHODS: We recruited participants in
the Netherlands with relatively mild insomnia disorder. After answering an online
pretest questionnaire, they were randomly assigned to the app (n=74) or the
waitlist condition (n=77). The app packaged a sleep diary, a relaxation exercise,
sleep restriction exercise, and sleep hygiene and education. The app was fully
automated and adjusted itself to a participant's progress. Program duration was 6
to 7 weeks, after which participants received posttest measurements and a 3-month
follow-up. The participants in the waitlist condition received the app after they
completed the posttest questionnaire. The measurements consisted of
questionnaires and 7-day online diaries. The questionnaires measured insomnia
severity, dysfunctional beliefs about sleep, and anxiety and depression symptoms.
The diary measured sleep variables such as sleep efficiency. We performed
multilevel analyses to study the interaction effects between time and condition.
RESULTS: The results showed significant interaction effects (P<.01) favoring the
app condition on the primary outcome measures of insomnia severity (d=-0.66) and
sleep efficiency (d=0.71). Overall, these improvements were also retained in a 3
month follow-up. CONCLUSIONS: This study demonstrated the efficacy of a fully
automated mobile phone app in the treatment of relatively mild insomnia. The
effects were in the range of what is found for Web-based treatment in general.
This supports the applicability of such technical tools in the treatment of
insomnia. Future work should examine the generalizability to a more diverse
population. Furthermore, the separate components of such an app should be
investigated. It remains to be seen how this app can best be integrated into the
current health regimens. TRIAL REGISTRATION: Netherlands Trial Register: NTR5560;
http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5560 (Archived by
WebCite at http://www.webcitation.org/6noLaUdJ4).
PMID- 28400356
TI - A Psychometric Analysis of the Italian Version of the eHealth Literacy Scale
Using Item Response and Classical Test Theory Methods.
AB - BACKGROUND: The eHealth Literacy Scale (eHEALS) is a tool to assess consumers'
comfort and skills in using information technologies for health. Although
evidence exists of reliability and construct validity of the scale, less
agreement exists on structural validity. OBJECTIVE: The aim of this study was to
validate the Italian version of the eHealth Literacy Scale (I-eHEALS) in a
community sample with a focus on its structural validity, by applying
psychometric techniques that account for item difficulty. METHODS: Two Web-based
surveys were conducted among a total of 296 people living in the Italian-speaking
region of Switzerland (Ticino). After examining the latent variables underlying
the observed variables of the Italian scale via principal component analysis
(PCA), fit indices for two alternative models were calculated using confirmatory
factor analysis (CFA). The scale structure was examined via parametric and
nonparametric item response theory (IRT) analyses accounting for differences
between items regarding the proportion of answers indicating high ability.
Convergent validity was assessed by correlations with theoretically related
constructs. RESULTS: CFA showed a suboptimal model fit for both models. IRT
analyses confirmed all items measure a single dimension as intended. Reliability
and construct validity of the final scale were also confirmed. The contrasting
results of factor analysis (FA) and IRT analyses highlight the importance of
considering differences in item difficulty when examining health literacy scales.
CONCLUSIONS: The findings support the reliability and validity of the translated
scale and its use for assessing Italian-speaking consumers' eHealth literacy.
PMID- 28400357
TI - Health Care Professionals' Evidence-Based Medicine Internet Searches Closely
Mimic the Known Seasonal Variation of Lyme Borreliosis: A Register-Based Study.
AB - BACKGROUND: Both health care professionals and nonprofessionals seek medical
information on the Internet. Using Web-based search engine searches to detect
epidemic diseases has, however, been problematic. Physician's databases (PD) is a
chargeable evidence-based medicine (EBM) portal on the Internet for health care
professionals and is available throughout the entire health care system in
Finland. Lyme borreliosis (LB), a well-defined disease model, shows temporal and
regional variation in Finland. Little data exist on health care professionals'
searches from Internet-based EBM databases in public health surveillance.
OBJECTIVE: The aim of this study was to assess whether health care professionals'
use of Internet EBM databases could describe seasonal increases of the disease
and supplement routine public health surveillance. METHODS: Two registers, PD and
the register of primary health care diagnoses (Avohilmo), were used to compare
health care professionals' Internet searches on LB from EBM databases and
national register-based LB diagnoses in order to evaluate annual and regional
variations of LB in the whole country and in three selected high-incidence LB
regions in Finland during 2011-2015. RESULTS: Both registers, PD and Avohilmo,
show visually similar patterns in annual and regional variation of LB in Finland
and in the three high-incidence LB regions during 2011-2015. CONCLUSIONS: Health
care professionals' Internet searches from EBM databases coincide with national
register diagnoses of LB. PD searches showed a clear seasonal variation. In
addition, notable regional differences were present in both registers. However,
physicians' Internet medical searches should be considered as a supplementary
source of information for disease surveillance.
PMID- 28400358
TI - A novel approach to the application of electroacupuncture in awake rats.
PMID- 28400359
TI - Unmet need for surgery in South Asia.
PMID- 28400360
TI - Are mental health tribunals only a nominal challenge?
PMID- 28400361
TI - Diabetes, cardiovascular disease, and chronic kidney disease in South Asia:
current status and future directions.
PMID- 28400362
TI - Raising taxes key to accelerate tobacco control in South Asia.
PMID- 28400363
TI - Nutrition in adolescent girls in South Asia.
PMID- 28400365
TI - Infographic: Return rates and return times to sport after Middle-Third clavicle
fracture: Important knowledge for management of these injuries in athletes.
PMID- 28400366
TI - Abnormal Remodeling of Subcutaneous Small Arteries Is Associated With Early
Diastolic Impairment in Metabolic Syndrome.
AB - BACKGROUND: Small artery pathophysiology is frequently invoked as a cause of
obesity-related diastolic heart failure. However, evidence to support this
hypothesis is scant, particularly in humans. METHODS AND RESULTS: To address
this, we studied human small artery structure and function in obesity and looked
for correlations between vascular parameters and diastolic function. Seventeen
obese patients with metabolic syndrome and 5 control participants underwent
echocardiography and subcutaneous gluteal fat biopsy. Small arteries were
isolated from the biopsy and pressure myography was used to study endothelial
function and wall structure. In comparison with the control group, small arteries
from obese participants exhibited significant endothelial dysfunction, assessed
as the vasodilatory response to acetylcholine and also pathological growth of the
wall. For the obese participants, multiple regression analysis revealed an
association between left atrial volume and both the small artery wall thickness
(beta=0.718, P=0.02) and wall-to-lumen ratio (beta=0.605, P=0.02). Furthermore,
the E:E' ratio was associated with wall-to-lumen ratio (beta=0.596, P=0.02) and
inversely associated with interleukin-6 (beta=-0.868, P=0.03). By contrast,
endothelial function did not correlate with any of the echocardiographic
parameters studied. CONCLUSIONS: Although the small arteries studied were not
cardiac in origin, our results support a role for small artery remodeling in the
development of diastolic dysfunction in humans. Further direct examination of the
structure and function of the myocardial resistance vasculature is now warranted,
to elucidate the temporal association between metabolic risk factors, small
artery injury, and diastolic impairment.
PMID- 28400367
TI - Health Literacy and Awareness of Atrial Fibrillation.
AB - BACKGROUND: Atrial fibrillation (AF) is the most common clinically significant
arrhythmia in adults and a major risk factor for ischemic stroke. Nonetheless,
previous research suggests that many individuals diagnosed with AF lack awareness
about their diagnosis and inadequate health literacy may be an important
contributing factor to this finding. METHODS AND RESULTS: We examined the
association between health literacy and awareness of an AF diagnosis in a large,
ethnically diverse cohort of Kaiser Permanente Northern and Southern California
adults diagnosed with AF between January 1, 2006 and June 30, 2009. Using self
reported questionnaire data completed between May 1, 2010 and September 30, 2010,
awareness of an AF diagnosis was evaluated using the question "Have you ever been
told by a doctor or other health professional that you have a heart rhythm
problem called atrial fibrillation or atrial flutter?" and health literacy was
assessed using a validated 3-item instrument examining problems because of
reading, understanding, and filling out medical forms. Of the 12 517 patients
diagnosed with AF, 14.5% were not aware of their AF diagnosis and 20.4% had
inadequate health literacy. Patients with inadequate health literacy were less
likely to be aware of their AF diagnosis compared with patients with adequate
health literacy (prevalence ratio=0.96; 95% CI [0.94, 0.98]), adjusting for
sociodemographics, health behaviors, and clinical characteristics. CONCLUSIONS:
Lower health literacy is independently associated with less awareness of AF
diagnosis. Strategies designed to increase patient awareness of AF and its
complications are warranted among individuals with limited health literacy.
PMID- 28400368
TI - Relationship Between Peak Troponin Values and Long-Term Ischemic Events Among
Medically Managed Patients With Acute Coronary Syndromes.
AB - BACKGROUND: The relationship between troponin level and outcomes among patients
with non-ST-segment elevation ACS is established, but the relationship of
troponin level with long-term outcomes among medically managed non-ST-segment
elevation ACS patients receiving contemporary antiplatelet therapy is
inadequately defined. METHODS AND RESULTS: In 6763 medically managed non-ST
segment elevation ACS patients randomized in TRILOGY ACS (Targeted Platelet
Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary
Syndromes) (prasugrel versus clopidogrel), we examined relationships between
categories of peak troponin/upper limit of normal (ULN) ratio within 48 hours of
the index ACS event (~4.5 days before randomization) and 30-month outcomes
(cardiovascular death, myocardial infarction, or stroke; cardiovascular death or
myocardial infarction; and all-cause death). Patients with peak troponin levels
<1*ULN were younger, were more often women, and had lower GRACE risk scores than
those in other troponin groups. Those with ratios >=5*ULN were more frequently
smokers but less often had prior myocardial infarction or percutaneous coronary
intervention. Diabetes mellitus prevalence, body mass index, serum creatinine,
and hemoglobin were similar across groups. For all end points, statistically
significant differences in 30-month event rates were observed between peak
troponin categories. The relationship was linear for 30-month mortality (<1*ULN,
n=1849 [6.2%]; 1 to <3*ULN, n=1203 [9.6%]; 3 to <5*ULN, n=581 [10.8%]; and
>=5*ULN, n=3405 [12.8%]) but plateaued for composite end points beyond peak
troponin values >=3*ULN. There was no statistically significant heterogeneity in
treatment effect by peak troponin ratio for any end point. CONCLUSIONS: Among
medically managed non-ST-segment elevation ACS patients selected for medical
management, there was a graded relationship between increasing peak troponin and
long-term ischemic events but no heterogeneity of treatment effect for prasugrel
versus clopidogrel according to peak troponin. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00699998.
PMID- 28400369
TI - In Utero Particulate Matter Exposure Produces Heart Failure, Electrical
Remodeling, and Epigenetic Changes at Adulthood.
AB - BACKGROUND: Particulate matter (PM; PM2.5 [PM with diameters of <2.5 MUm])
exposure during development is strongly associated with adverse cardiovascular
outcomes at adulthood. In the present study, we tested the hypothesis that in
utero PM2.5 exposure alone could alter cardiac structure and function at
adulthood. METHODS AND RESULTS: Female FVB mice were exposed either to filtered
air or PM2.5 at an average concentration of 73.61 MUg/m3 for 6 h/day, 7 days/week
throughout pregnancy. After birth, animals were analyzed at 12 weeks of age.
Echocardiographic (n=9-10 mice/group) and pressure-volume loop analyses (n=5
mice/group) revealed reduced fractional shortening, increased left ventricular
end-systolic and -diastolic diameters, reduced left ventricular posterior wall
thickness, end-systolic elastance, contractile reserve (dP/dtmax/end-systolic
volume), frequency-dependent acceleration of relaxation), and blunted contractile
response to beta-adrenergic stimulation in PM2.5-exposed mice. Isolated
cardiomyocyte (n=4-5 mice/group) function illustrated reduced peak shortening, +/
dL/dT, and prolonged action potential duration at 90% repolarization.
Histological left ventricular analyses (n=3 mice/group) showed increased collagen
deposition in in utero PM2.5-exposed mice at adulthood. Cardiac interleukin (IL)
6, IL-1beta, collagen-1, matrix metalloproteinase (MMP) 9, and MMP13 gene
expressions were increased at birth in in utero PM2.5-exposed mice (n=4
mice/group). In adult hearts (n=5 mice/group), gene expressions of sirtuin (Sirt)
1 and Sirt2 were decreased, DNA methyltransferase (Dnmt) 1, Dnmt3a, and Dnmt3b
were increased, and protein expression (n=6 mice/group) of Ca2+-ATPase,
phosphorylated phospholamban, and Na+/Ca2+ exchanger were decreased. CONCLUSIONS:
In utero PM2.5 exposure triggers an acute inflammatory response, chronic matrix
remodeling, and alterations in Ca2+ handling proteins, resulting in global adult
cardiac dysfunction. These results also highlight the potential involvement of
epigenetics in priming of adult cardiac disease.
PMID- 28400370
TI - The role of specific visual subfields in collisions with oncoming cars during
simulated driving in patients with advanced glaucoma.
AB - BACKGROUND/AIMS: To assess the role of specific visual subfields in collisions
with oncoming cars during simulated driving in patients with advanced glaucoma.
METHODS: Normal subjects and patients with glaucoma with mean deviation <-12 dB
in both eyes (Humphrey Field Analyzer 24-2 SITA-S program) used a driving
simulator (DS; Honda Motor, Tokyo). Two scenarios in which oncoming cars turned
right crossing the driver's path were chosen. We compared the binocular
integrated visual field (IVF) in the patients who were involved in collisions and
those who were not. We performed a multivariate logistic regression analysis; the
dependent parameter was collision involvement, and the independent parameters
were age, visual acuity and mean sensitivity of the IVF subfields. RESULTS: The
study included 43 normal subjects and 100 patients with advanced glaucoma. And, 5
of the 100 patients with advanced glaucoma experienced simulator sickness during
the main test and were thus excluded. In total, 95 patients with advanced
glaucoma and 43 normal subjects completed the main test of DS. Advanced glaucoma
patients had significantly more collisions than normal patients in one or both DS
scenarios (p<0.001). The patients with advanced glaucoma who were involved in
collisions were older (p=0.050) and had worse visual acuity in the better eye
(p<0.001) and had lower mean IVF sensitivity in the inferior hemifield, both 0
degrees -12 degrees and 13 degrees -24 degrees in comparison with who were not
involved in collisions (p=0.012 and p=0.034). A logistic regression analysis
revealed that collision involvement was significantly associated with decreased
inferior IVF mean sensitivity from 13 degrees to 24 degrees (p=0.041), in
addition to older age and lower visual acuity (p=0.018 and p<0.001). CONCLUSIONS:
Our data suggest that the inferior hemifield was associated with the incidence of
motor vehicle collisions with oncoming cars in patients with advanced glaucoma.
PMID- 28400371
TI - Retinal microvascular network geometry and cognitive abilities in community
dwelling older people: The Lothian Birth Cohort 1936 study.
AB - AIM: To examine the relationship between retinal vascular morphology and
cognitive abilities in a narrow-age cohort of community-dwelling older people.
METHODS: Digital retinal images taken at age ~73 years from 683 participants of
the Lothian Birth Cohort 1936 (LBC1936) were analysed with Singapore I Vessel
Assessment (SIVA) software. Multiple regression models were applied to determine
cross-sectional associations between retinal vascular parameters and general
cognitive ability (g), memory, processing speed, visuospatial ability,
crystallised cognitive ability and change in IQ from childhood to older age.
RESULTS: After adjustment for cognitive ability at age 11 years and
cardiovascular risk factors, venular length-to-diameter ratio was nominally
significantly associated with processing speed (beta=-0.116, p=0.01) and g (beta=
0.079, p=0.04). Arteriolar length-to-diameter ratio was associated with
visuospatial ability (beta=0.092, p=0.04). Decreased arteriolar junctional
exponent deviation and increased arteriolar branching coefficient values were
associated with less relative decline in IQ between childhood and older age
(arteriolar junctional exponent deviation: beta=-0.101, p=0.02; arteriolar
branching coefficient: beta=0.089, p=0.04). Data are presented as standardised
beta coefficients (beta) reflecting change in cognitive domain score associated
with an increase of 1 SD unit in retinal parameter. None of these nominally
significant associations remained significant after correction for multiple
statistical testing. CONCLUSIONS: Retinal parameters contributed <1% of the
variance in the majority of associations observed. Whereas retinal analysis may
have potential for early detection of some types of age-related cognitive decline
and dementia, our results present little evidence that retinal vascular features
are associated with non-pathological cognitive ageing.
PMID- 28400372
TI - Risk factors for bleb-related infection following trabeculectomy surgery: ocular
surface findings-a case-control study.
AB - PURPOSE: Bleb-related infection (BRI) is a devastating complication of
trabeculectomy surgery. The aim of this study was to identify ocular risk factors
for BRI with specific emphasis on ocular surface parameters. It has been
suggested that the frequency has increased since the introduction of
antimetabolites, particularly mitomycin C. DESIGN: A case-control study. METHOD:
A clinical study of BRI following trabeculectomy surgery to investigate risk
factors by documenting historical data review from patients records, self
reported questionnaire specific to ocular surface symptoms and a repeat detailed
clinical examination of the lid, ocular surface and tear film. RESULTS: Twenty
eight cases and 31 controls were assessed. The overwhelming risk factor for
development of BRI was chronic blepharitis (multivariate analysis OR 16.3 (1.687
to 157.44) p=0.016). No increased risk was identified with the antimetabolite
used during trabeculectomy surgery (p=0.38) or the type of conjunctival
reflection adopted for surgery (p=0.38). Neither age (p=0.32) nor dry eyes
(p=0.13) were identified as risk factors. CONCLUSION: An increased risk of BRI
was identified in eyes with chronic blepharitis. To minimise the risk of
infection following trabeculectomy surgery, it may be advisable to manage the lid
disease in these patients prior to performing trabeculectomy surgery or offer an
alternative treatment such as a shunt. TRIAL REGISTRATION NUMBER: RAIQ1001.
PMID- 28400373
TI - Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of
neovascular AMD with anti-VEGF agents: a meta-analysis.
AB - AIMS: The purpose of this study is to investigate whether gene polymorphisms of
the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have
a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related
macular degeneration (nAMD). METHODS: We carried out a meta-analysis focusing on
the relationship between VEGF-related gene polymorphisms and treatment response
of nAMD. RESULTS: For the single nucleotide polymorphisms (SNPs) within VEGF-A
and VEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD
having rs833061 (CC vs TT:OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT:
OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414
to 3.946, p=0.001), particularly for Asians (CC vs TT: OR=2.903, 95% CI 1.150 to
7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs
CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In subgroup
analysis, rs833061 was more likely to be a predictor of response to anti-VEGF
therapy specifically when ranibizumab (RBZ) only regime was adopted or visual
acuity (VA) was taken as the standardised assessment of outcome. No association
with response to anti-VEGF treatment was detected for the other eight
polymorphisms. CONCLUSIONS: Pharmacogenetics of VEGF-A polymorphism rs833061 may
play a positive role in response to anti-VEGF therapy for nAMD.
PMID- 28400374
TI - Aqueous outflow facility after phacoemulsification with or without
goniosynechialysis in primary angle closure: a randomised controlled study.
AB - BACKGROUND: Goniosynechialysis (GSL) to remove peripheral anterior synechiae
(PAS) alongside standard cataract surgery has potential theoretical advantages,
Published randomised trials, however, have not shown conclusive functional
benefits and aqueous outflow changes following GSL are unknown. This study aimed
to compare electronic Shiotz tonographic aqueous outflow facility (TOF) following
phacoemulsification with or without GSL in patients with primary angle closure
(PAC) and PAC glaucoma. Secondary outcomes were changes in intraocular pressure
(IOP) and use of glaucoma medications. METHODS: Prospective randomised pilot
study of 26 patients on glaucoma medication, with >=90 degrees PAS and
significant lens opacity. Patients were randomised 1:1 to receive
phacoemulsification with intraocular lens (IOL) implantation only (phaco) or
phacoemulsification with IOL plus GSL (phaco-GSL). RESULTS: Fourteen patients
were randomised to phaco-GSL and 12 to phaco alone. TOF increased with phaco-GSL
from 0.099+/-0.07 MUL/min/mm Hg to 0.194+/-0.07, MUL/min/mm Hg, p=0.0006, while
the phaco group showed no significant change. IOP reduced in both groups, but
reduced significantly more following phaco-GSL (46.0%) compared with phaco alone
(27.6%, p=0.04). Medication use and extent of PAS only reduced with phaco-GSL,
from 0.923+/-0.86 to 0.384+/-0.18 medications, p=0.0279, and from 249.2+/-83.4 to
110.8+/-53.9 degrees PAS, 6 months postoperatively. No serious adverse events
occurred in either group. CONCLUSIONS: Eyes randomised to both surgical groups
had similar and good outcomes at 6 months in this pilot study. However, only eyes
undergoing GSL combined with standard phacoemulsification had significantly
increased TOF, reduced glaucoma medication dependence and PAS postoperatively.
GSL should therefore be considered in such patients. TRIAL REGISTRATION NUMBER:
NCT00719290, Results.
PMID- 28400377
TI - Expanding access to healthcare in South Asia.
PMID- 28400376
TI - Therapy reduction in patients with Down syndrome and myeloid leukemia: the
international ML-DS 2006 trial.
AB - Children with myeloid leukemia associated with Down syndrome (ML-DS) have
superior outcome compared with non-DS patients, but suffer from higher
constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170
pediatric patients with ML-DS enrolled in the prospective, multicenter, open
label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology
and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid
Leukemia-Berlin-Frankfurt-Munster (AML-BFM) study group. Compared with the
historical control arm (reduced-intensity protocol for ML-DS patients from the
AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative
dose of etoposide (950 to 450 mg/m2) and intrathecal central nervous system
prophylaxis while omitting maintenance therapy. Still, 5-year overall survival
(89% +/- 3% vs 90% +/- 4%; Plog-rank = .64), event-free survival (EFS; 87% +/- 3%
vs 89% +/- 4%; Plog-rank = .71), and cumulative incidence of relapse/nonresponse
(CIR/NR; 6% +/- 3% vs 6% +/- 2%; PGray = .03) did not significantly differ
between the ML-DS 2006 trial and the historical control arm. Poor early treatment
response (5-year EFS, 58% +/- 16% vs 88% +/- 3%; Plog rank = .0008) and gain of
chromosome 8 (CIR/NR, 16% +/- 7% vs 3% +/- 2%, PGray = .02; 5-year EFS, 73% +/-
8% vs 91% +/- 4%, Plog rank = .018) were identified as independent prognostic
factors predicting a worse EFS. Five of 7 relapsed patients (71%) with
cytogenetic data had trisomy 8. Our study reveals prognostic markers for children
with ML-DS and illustrates that reducing therapy did not impair excellent
outcome. The trial was registered at EudraCT as #2007-006219-2.
PMID- 28400375
TI - Continuous blockade of CXCR4 results in dramatic mobilization and expansion of
hematopoietic stem and progenitor cells.
AB - Interaction between the chemokine receptor CXCR4 and its chief ligand CXCL12
plays a critical role in the retention and migration of hematopoietic stem and
progenitor cells (HSPCs) in the bone marrow (BM) microenvironment. In this study,
qualitative and quantitative effects of long-term pharmacologic inhibition of the
CXCR4/CXCL12 axis on the HSPC compartment were investigated by using 3
structurally unrelated small molecule CXCR4 antagonists. A >10-fold increase in
mobilization efficiency was achieved by administering the antagonists as a
subcutaneous continuous infusion for 2 weeks compared to a single bolus
injection. A concurrent increase in self-renewing proliferation leading to a
twofold to fourfold expansion of the HSPC pool in the BM was observed. The
expanded BM showed a distinct repopulating advantage when tested in serial
competitive transplantation experiments. Furthermore, major changes within the
HSPC niche associated with previously described HSPC expansion strategies were
not detected in bones treated with a CXCR4 antagonist infusion. Our data suggest
that prolonged but reversible pharmacologic blockade of the CXCR4/CXCL12 axis
represents an approach that releases HSPC with efficiency superior to any other
known mobilization strategy and may also serve as an effective method to expand
the BM HSPC pool.
PMID- 28400378
TI - How should mandatory sex education be taught?
PMID- 28400379
TI - Mental illness and injuries: emerging health challenges of urbanisation in South
Asia.
PMID- 28400382
TI - Scotland's approval of PrEP creates postcode lottery in UK, say campaigners.
PMID- 28400380
TI - Conflict in South Asia and its impact on health.
PMID- 28400383
TI - On the brink of conflict: the people of South Asia deserve better.
PMID- 28400384
TI - Stroke in systemic lupus erythematosus: a Swedish population-based cohort study.
AB - OBJECTIVE: To study the occurrence of ischaemic and haemorrhagic stroke in
systemic lupus erythematosus (SLE) compared with the general population by age,
sex and time since SLE diagnosis METHODS: Adults with incident SLE were
identified from the Swedish National Patient Register (NPR, n=3390) and general
population comparators from the Total Population Register were matched on age,
sex and county (n=16730). Individuals were followed prospectively until first of
death, December 2013, emigration or incident stroke (identified from the NPR,
Cause of Death Register and the Stroke Register). Incidence rates, rate
differences and HR were estimated comparing SLE with non-SLE. Estimates were
stratified by sex, age and time since diagnosis. RESULTS: We observed 126 strokes
in SLE and 304 in the general population. Individuals with SLE had a twofold
increased rate of ischaemic stroke compared with the general population (HR 2.2;
95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to
2.8). There was effect modification by sex and age, with the highest HRs for
females and individuals <50 years old. The HR for ischaemic stroke was highest in
the first year of follow-up (3.7; 95% CI 2.1 to 6.5). CONCLUSIONS: The relative
risk of ischaemic stroke in SLE was more than doubled compared with the general
population, and importantly, the highest relative risks were observed within the
first year after SLE diagnosis. Thus, the first encounter with patients presents
an opportunity for rheumatologists to screen for risk factors and intervene.
PMID- 28400385
TI - The rise of private medicine in South Asia.
PMID- 28400386
TI - Emerging and re-emerging infectious disease threats in South Asia: status,
vulnerability, preparedness, and outlook.
PMID- 28400387
TI - David Oliver: Challenges for rural hospitals--the same but different.
PMID- 28400388
TI - The term "health based place of safety" is meaningless and hides the problem.
PMID- 28400389
TI - Hereditary leiomyomatosis and renal cell cancer (HLRCC): cutaneous and renal
manifestations requiring a multidisciplinary team approach.
AB - Cutaneous leiomyomasare rare tumours of smooth muscle origin associated with
disorders such as hereditary leiomyomatosis and renal cell cancer (HLRCC)
syndrome. HLRCC is an autosomal dominant syndrome caused by loss of function
mutations in the fumarate hydratase gene. Sufferers of this disorder are
predisposed to the development of tumours of the skin and/or uterus, with a
further subset of HLRCC families at risk of renal cell carcinoma with papillary
features. This syndrome is rare and carries with it a significant rate of
mortality. A multidisciplinary approach to care is critical in the management of
these patients and their families. The dermatologist can play a central role in
this process, coordinating care between specialist medical and allied health
teams.
PMID- 28400390
TI - Alopecia neoplastica.
PMID- 28400391
TI - Mood Zoom could be a promising tool for daily mood variability monitoring,
potentially differentiating bipolar from borderline patients.
PMID- 28400393
TI - Health research priorities and gaps in South Asia.
PMID- 28400394
TI - Urethrocutaneous fistula mimicking vesicocutaneous fistula: a rare entity.
AB - Urethral fistulas arising from the anterior urethra usually open on the ventral
aspect and are located in the penile, scrotal or perineal region. A diabetic 65
year-old man presented with suprapubic urinary fistula that was communicating
with a dorsally located internal urethral opening located in the bulbar region.
Such unusual fistula has not been described before.
PMID- 28400392
TI - Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis.
AB - Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the
developed world's working adult population and affects those with type 1 and type
2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene
upregulated in CD31+ vascular endothelial cells obtained from human PDR
fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies
using human retinal microvascular endothelial cells (HRMECs) showed increased
RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1
inhibition reduced HRMEC migration, proliferation, and tube formation.
Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient
derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced
retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal
angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule
resulted in a significant reduction of neovascular tufts in oxygen-induced
retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal
angiogenesis.
PMID- 28400395
TI - Rapidly enlarging acquired capillary hemangioma of the eyelid.
PMID- 28400396
TI - Giant perforated marginal ulcer after laparoscopic Roux-en-Y gastric bypass.
AB - Perforation of a marginal ulcer (MU) is a complication of Roux-en-Y gastric
bypass that can be life-threatening. We report a case of a perforated MU that
presented 7 months after surgery with several interesting points for discussion.
Firstly, the presentation of the ulcer was cryptic with unreliable
investigations. Secondly, the ulcer presented again even after anastomotic
revision surgery. Finally, the ulcer and the sepsis associated with perforation
presented after months of poor nutritional intake with profound hypoalbuminaemia.
Perforated MUs causing malnutrition pose clinicians with the difficult decision
of which operation to offer; patch repair, revision of the anastomosis or
reversal surgery. This case illustrates that primary reversal surgery for a
perforated recurrent MU may be the most appropriate surgical management in this
clinical situation.
PMID- 28400397
TI - Fluorescence in a cryptococcoma following administration of 5-aminolevulinic acid
hydrochloride (Gliolan).
AB - A 54-year-old man presented with two episodes of dysarthria and left facial
droop. Both episodes resolved by the time of examination. MRI of the brain
revealed a right frontotemporal, heterogeneously enhancing mass with surrounding
vasogenic oedema, suggestive of a high-grade primary brain neoplasm. The patient
was administered preoperative 5-aminolevulinic acid hydrochloride (Gliolan), and
fluorescence-guided resection of the lesion was undertaken. Cryptococcus gattii
infection was diagnosed from the specimen and the patient was given appropriate
antifungal treatment. This is the first reported case of Gliolan-mediated
fluorescence in a fungal abscess and highlights one of the potential pitfalls in
fluorescence-guided surgery.
PMID- 28400399
TI - Cardiotoxicity with Itraconazole.
AB - Itraconazole is a commonly used antifungal drug. In addition to commonly
described adverse effects, there have been few reports of heart failure with its
use. We present two cases that developed acute systolic heart failure with
Itraconazole use. A man in his early 30s was admitted with worsening leg swelling
and dyspnoea on exertion. He had been on Itraconazole for blastomyces skin ulcer.
His ejection fraction (EF) was found to be 10%-15%. Another man in his 50s was
admitted with similar symptoms; his EF was 40%-45%. He had been on Itraconazole
for forearm cellulitis. No other aetiology was identified in both patients
despite extensive work-up including cardiac catheterisation. Itraconazole was
stopped in both the cases. Our first patient did not improve even months after
cessation of therapy and was referred for heart transplant. Our second patient
improved after a few weeks, and his ejection fraction had improved on repeat
testing.
PMID- 28400398
TI - Multi-Imaging Method to Assay the Contractile Mechanical Output of Micropatterned
Human iPSC-Derived Cardiac Myocytes.
AB - RATIONALE: During each beat, cardiac myocytes (CMs) generate the mechanical
output necessary for heart function through contractile mechanisms that involve
shortening of sarcomeres along myofibrils. Human-induced pluripotent stem cells
(hiPSCs) can be differentiated into CMs (hiPSC-CMs) that model cardiac
contractile mechanical output more robustly when micropatterned into
physiological shapes. Quantifying the mechanical output of these cells enables us
to assay cardiac activity in a dish. OBJECTIVE: We sought to develop a
computational platform that integrates analytic approaches to quantify the
mechanical output of single micropatterned hiPSC-CMs from microscopy videos.
METHODS AND RESULTS: We micropatterned single hiPSC-CMs on deformable
polyacrylamide substrates containing fluorescent microbeads. We acquired videos
of single beating cells, of microbead displacement during contractions, and of
fluorescently labeled myofibrils. These videos were independently analyzed to
obtain parameters that capture the mechanical output of the imaged single cells.
We also developed novel methods to quantify sarcomere length from videos of
moving myofibrils and to analyze loss of synchronicity of beating in cells with
contractile defects. We tested this computational platform by detecting
variations in mechanical output induced by drugs and in cells expressing low
levels of myosin-binding protein C. CONCLUSIONS: Our method can measure the
cardiac function of single micropatterned hiPSC-CMs and determine contractile
parameters that can be used to elucidate mechanisms that underlie variations in
CM function. This platform will be amenable to future studies of the effects of
mutations and drugs on cardiac function.
PMID- 28400400
TI - Transperineal aggressive angiomyxoma.
AB - A 45-year-old woman with a history of total hysterectomy with adnexal
preservation for uterine leiomyomas presented to our hospital with a right
gluteal palpable mass, which she first noticed 6 months before and had
progressively enlarged since then.Radiological studies revealed a 14 cm lesion
with translevator growth that displaced rather than invaded adjacent structures,
with a peculiar whorled pattern on T2-weighted MRI, which enhanced following
gadolinium administration. CT-guided biopsy was performed, and in conjunction
with imaging features the diagnosis of an aggressive angiomyxoma was assumed and
confirmed following surgical excision.
PMID- 28400401
TI - TRAIL- and TNF-induced signaling complexes-so similar yet so different.
PMID- 28400402
TI - Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies.
AB - Tumourigenesis is a relatively common event in endocrine tissues. Currently,
specific guidelines have been developed for common malignant endocrine tumours,
which also incorporate advances in molecular targeted therapies (MTT), as in
thyroid cancer and in gastrointestinal neuroendocrine malignancies. However,
there is little information regarding the role and efficacy of MTT in the
relatively rare malignant endocrine tumours mainly involving the adrenal medulla,
adrenal cortex, pituitary, and parathyroid glands. Due to the rarity of these
tumours and the lack of prospective studies, current guidelines are mostly based
on retrospective data derived from surgical, locoregional and ablative therapies,
and studies with systemic chemotherapy. In addition, in many of these
malignancies the prognosis remains poor with individual patients responding
differently to currently available treatments, necessitating the development of
new personalised therapeutic strategies. Recently, major advances in the
molecular understanding of endocrine tumours based on genomic, epigenomic, and
transcriptome analysis have emerged, resulting in new insights into their
pathogenesis and molecular pathology. This in turn has led to the use of novel
MTTs in increasing numbers of patients. In this review, we aim to present
currently existing and evolving data using MTT in the treatment of adrenal,
pituitary and malignant parathyroid tumours, and explore the current utility and
effectiveness of such therapies and their future evolution.
PMID- 28400403
TI - Molecular imaging in the investigation of hypoglycaemic syndromes and their
management.
AB - There has been recent progress in molecular imaging using a variety of cellular
targets for the investigation of adult non-diabetic hypoglycaemic syndromes and
its integration into patient management. These targets include peptide receptors
(somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R))
the amine precursor uptake and decarboxylation system utilising the
diphydroxyphenylaline (DOPA) analogue 6-[18F]-l-fluoro-l-3,4
dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]fluoro
2-deoxy-d-glucose (FDG). Accurate preoperative localisation and staging is
critical to enable directed surgical excision or enucleation with minimal
morbidity and preservation of residual pancreatic function. Benign insulinoma has
near ubiquitous dense GLP-1R expression enabling accurate localisation with
radiolabelled-exendin-4 compounds (e.g. 68Ga-NOTA-exendin-4 PET/CT), whilst the
rarer and more difficult to manage metastatic insulinoma typically express SSTR
and is preferably imaged with radiolabelled-SSTR analogues such as 68Ga-DOTA
octreotate (DOTATATE) PET/CT for staging and assessment of suitability for
peptide receptor radionuclide therapy (PRRT). Similar to other metastatic
neuroendocrine tumours, FDG PET/CT is used in the setting of higher-grade
metastatic insulinoma to provide important prognostic information that can guide
treatment and determine suitability for PRRT. Interestingly, these three tracers
appear to represent a spectrum of differentiation, which we conceptually describe
as the 'triple-flop' phenomenon, with GLP-1R > SSTR > FDG in benign insulinoma
and the opposite in higher-grade disease. This paper will review the clinical
syndromes of adult hypoglycaemia (including a practical overview of the
differential diagnoses to be considered), comparison of techniques for insulinoma
localisation with emphasis on molecular imaging before discussing its
implications for management of metastatic insulinoma.
PMID- 28400404
TI - A growth mindset approach to preparing trainees for medical error.
PMID- 28400406
TI - Pillow talk.
PMID- 28400407
TI - The BMJ Awards 2017: Surgery.
PMID- 28400410
TI - Research integrity revisited.
PMID- 28400408
TI - Incidence and Risk Factors for Cardiovascular Collapse After Unplanned
Extubations in the Pediatric ICU.
AB - BACKGROUND: Cardiovascular collapse is a life-threatening event after unplanned
extubations (UEs) in the pediatric ICU (PICU). However, there is a paucity of
pediatric studies assessing this complication. We sought to assess the incidence,
risk factors, and outcome of cardiovascular collapse after UEs in PICU patients.
METHODS: All children who had been mechanically ventilated for >=12 h were
prospectively tracked for UEs over an 8-y period. Subjects were included in the
study if they were between ages 1 month and 16 y and had experienced UE. They
were analyzed in 2 groups: those with cardiovascular collapse (defined as the
need for cardiopulmonary resuscitation or circulatory dysfunction immediately
after UE) and those with no cardiovascular collapse. RESULTS: Of the 847
subjects, 109 UEs occurred in 14,293 intubation days (0.76 UEs/100 intubation
days), with 21 subjects (19.2%) experiencing cardiovascular collapse, of which 10
required cardiopulmonary resuscitation. Compared with subjects without
cardiovascular collapse after UE, children with cardiovascular collapse were
younger (<6 months old), with respiratory failure from lower respiratory tract
diseases, lower PaO2/FIO2 (218 vs 282 mm Hg), and higher oxygenation indices (5.5
vs 3.5) before UE events. Logistic regression revealed that only an age <=6
months old was strongly associated with cardiovascular collapse (odds ratio 3.4,
P = .03). There were no differences between cardiovascular collapse and non
cardiovascular collapse subjects regarding the length of hospital stay,
ventilator-associated pneumonia rate, and mortality. CONCLUSIONS: Cardiovascular
collapse is a frequent complication of UEs, particularly in the youngest
children. Specific bundles to prevent UEs may reduce morbidity related to these
events.
PMID- 28400409
TI - DROSHA targets its own transcript to modulate alternative splicing.
AB - The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the
Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving
hairpin structures embedded in primary transcripts. Apart from its central role
in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA
like hairpins in a subset of transcripts without apparent small RNA production.
Here, we report that the human DROSHA transcript is one such noncanonical target
of DROSHA. Mammalian DROSHA genes have evolved a conserved hairpin structure
spanning a specific exon-intron junction, which serves as a substrate for the
Microprocessor in human cells but not in murine cells. We show that it is this
hairpin element that decides whether the overlapping exon is alternatively or
constitutively spliced. We further demonstrate that DROSHA promotes skipping of
the overlapping exon in human cells independently of its cleavage function. Our
findings add to the expanding list of noncanonical DROSHA functions.
PMID- 28400411
TI - Fatty acid uptake and blood flow in adipose tissue compartments of morbidly obese
subjects with or without type 2 diabetes: effects of bariatric surgery.
AB - Body fat accumulation, distribution, and metabolic activity are factors in the
pathophysiology of obesity and type 2 diabetes (T2D). We investigated adipose
blood flow, fatty acid uptake (FAU), and subcutaneous and visceral fat
cellularity in obese patients with or without T2D. A total of 23 morbidly obese
(mean body mass index = 42 kg/m2) patients were studied before and 6 mo after
bariatric surgery; 15 nonobese subjects served as controls. Positron emission
tomography was used to measure tissue FAU (with 18F-FTHA) and blood flow (with
H215O); MRI was used for fat distribution and fat biopsy for adipocyte size.
Obese subjects had subcutaneous hyperplasia and hypertrophy and lower blood flow;
when expressed per cell, flow was similar to controls. FAU into subcutaneous and
visceral depots was increased in the obese; per unit tissue mass, however, FAU
was similar to controls but reduced in skeletal muscle. Fatty acid fractional
extraction in subcutaneous fat and muscle was only increased in obese patients
with T2D. We conclude that surgery reduces subcutaneous fat hyperplasia and
hypertrophy; subcutaneous blood flow and FAU decrease in absolute terms and per
cell while fractional FAU remains unchanged in T2D. In the obese, subcutaneous
blood flow is a determinant of FAU and is coupled with cellularity; efficiency of
FAU is enhanced in subcutaneous fat and muscle in T2D.
PMID- 28400405
TI - Nutritional approaches for managing obesity-associated metabolic diseases.
AB - Obesity is an ongoing pandemic and serves as a causal factor of a wide spectrum
of metabolic diseases including diabetes, fatty liver disease, and cardiovascular
disease. Much evidence has demonstrated that nutrient overload/overnutrition
initiates or exacerbates inflammatory responses in tissues/organs involved in the
regulation of systemic metabolic homeostasis. This obesity-associated
inflammation is usually at a low-grade and viewed as metabolic inflammation. When
it exists continuously, inflammation inappropriately alters metabolic pathways
and impairs insulin signaling cascades in peripheral tissues/organs such as
adipose tissue, the liver and skeletal muscles, resulting in local fat deposition
and insulin resistance and systemic metabolic dysregulation. In addition,
inflammatory mediators, e.g., proinflammatory cytokines, and excessive nutrients,
e.g., glucose and fatty acids, act together to aggravate local insulin resistance
and form a vicious cycle to further disturb the local metabolic pathways and
exacerbate systemic metabolic dysregulation. Owing to the critical role of
nutrient metabolism in controlling the initiation and progression of inflammation
and insulin resistance, nutritional approaches have been implicated as effective
tools for managing obesity and obesity-associated metabolic diseases. Based on
the mounting evidence generated from both basic and clinical research,
nutritional approaches are commonly used for suppressing inflammation, improving
insulin sensitivity, and/or decreasing fat deposition. Consequently, the combined
effects are responsible for improvement of systemic insulin sensitivity and
metabolic homeostasis.
PMID- 28400412
TI - Western-diet consumption induces alteration of barrier function mechanisms in the
ileum that correlates with metabolic endotoxemia in rats.
AB - Obesity and its related disorders have been associated with the presence in the
blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors
underlying this low-grade elevation in plasma LPS, so-called metabolic
endotoxemia, are not fully elucidated. We aimed to investigate the effects of
Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a
rat model of diet-induced obesity (DIO). Rats were fed either a standard chow
diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad
libitum or pair-fed to match the caloric intake of C rats for the first week,
then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild
obese phenotype with increased adiposity and elevated serum LPS-binding protein
(LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS
was not different between dietary groups but exhibited strong variability.
Disrupted ileal mucus secretion and decreased ileal Reg3-gamma and -beta gene
expression along with high ileal permeability to LPS were observed in WD compared
with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity
as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD
fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of
LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of
LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression
correlated with serum LPS and LBP, suggesting that ileal mucosal defense
impairment induced by WD feeding contribute to metabolic endotoxemia.
PMID- 28400413
TI - High-throughput phenotyping.
PMID- 28400414
TI - Differences in dehydration tolerance among populations of a gametophyte-only
fern.
AB - PREMISE OF THE STUDY: For many plant species, historical climatic conditions may
have left lasting imprints that are detectable in contemporary populations.
Additionally, if these historical conditions also prevented gene flow among
populations, these populations may be differentiated with respect to one another
and their contemporary environmental conditions. For the fern, Vittaria
appalachiana, one theory is that historical conditions during the Pleistocene
largely shaped both the distribution and lack of sporophyte production. Our goals
based on this theory-were to examine physiological differences among and within
populations spanning the species' geographic range, and the contribution of
historical climatic conditions to this differentiation. METHODS: We exposed
explants from five populations to four drying treatments and examined differences
in physiological response. Additionally, we examined the role of historical and
current climatic conditions in driving the observed population differentiation.
KEY RESULTS: Populations differ in their ability to tolerate varying levels of
dehydration, displaying a pattern of countergradient selection. Exposure to
historical and contemporary climatic conditions, specifically variation in
temperature and precipitation regimes, resulted in population divergence observed
among contemporary populations. CONCLUSIONS: Historical conditions have shaped
not only the distribution of V. appalachiana, but also its current physiological
limitations. Results from this study support the hypothesis that climatic
conditions during the Pleistocene are responsible for the distribution of this
species, and may be responsible for the observed differences in dehydration
tolerance. Additionally, dehydration tolerance may be the driving factor for
previously reported patterns of countergradient selection in this species.
PMID- 28400415
TI - Recombination-dependent replication and gene conversion homogenize repeat
sequences and diversify plastid genome structure.
AB - PREMISE OF THE STUDY: There is a misinterpretation in the literature regarding
the variable orientation of the small single copy region of plastid genomes
(plastomes). The common phenomenon of small and large single copy inversion,
hypothesized to occur through intramolecular recombination between inverted
repeats (IR) in a circular, single unit-genome, in fact, more likely occurs
through recombination-dependent replication (RDR) of linear plastome templates.
If RDR can be primed through both intra- and intermolecular recombination, then
this mechanism could not only create inversion isomers of so-called single copy
regions, but also an array of alternative sequence arrangements. METHODS: We used
Illumina paired-end and PacBio single-molecule real-time (SMRT) sequences to
characterize repeat structure in the plastome of Monsonia emarginata
(Geraniaceae). We used OrgConv and inspected nucleotide alignments to infer
ancestral nucleotides and identify gene conversion among repeats and mapped long
(>1 kb) SMRT reads against the unit-genome assembly to identify alternative
sequence arrangements. RESULTS: Although M. emarginata lacks the canonical IR, we
found that large repeats (>1 kilobase; kb) represent ~22% of the plastome
nucleotide content. Among the largest repeats (>2 kb), we identified GC-biased
gene conversion and mapping filtered, long SMRT reads to the M. emarginata unit
genome assembly revealed alternative, substoichiometric sequence arrangements.
CONCLUSION: We offer a model based on RDR and gene conversion between long
repeated sequences in the M. emarginata plastome and provide support that both
intra-and intermolecular recombination between large repeats, particularly in
repeat-rich plastomes, varies unit-genome structure while homogenizing the
nucleotide sequence of repeats.
PMID- 28400416
TI - Medical Centers Sign On to Single IRB Model.
AB - All 64 member institutions of the NIH's Clinical and Translational Science Awards
program have agreed to a common framework for running multisite trials under the
umbrella of just one Institutional Review Board. The NCI has long offered a
centralized review board option. Come September, single Institutional Review
Boards will be mandatory for all NIH-backed studies.
PMID- 28400417
TI - CAR T-cell Therapy: Defining Response Characteristics.
AB - Findings from a phase I study suggest that the durability of patients' response
to CAR T-cell therapy, and their long-term survival, are influenced by whether
they have minimal residual or morphologic disease prior to treatment. The former
fared better overall, and also experienced less-severe side effects from this
form of immunotherapy.
PMID- 28400418
TI - The BMJ Awards 2017: UK Research Paper.
PMID- 28400419
TI - Thomas Starzl.
PMID- 28400420
TI - Penny for Your Thoughts; A Coin in the Stomach: Why Did It Get Stuck?
PMID- 28400421
TI - Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic
Cohort of Pregnant Patients with Lupus.
AB - BACKGROUND AND OBJECTIVES: Kidney disease is a critical concern in counseling
patients with lupus considering pregnancy. This study sought to assess the risk
of renal flares during pregnancy in women with previous lupus nephritis in
partial or complete remission, particularly in those with antidouble-stranded DNA
antibodies and low complement levels, and the risk of new-onset nephritis in
patients with stable/mildly active SLE. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: We assessed active nephritis (renal flares and de novo kidney
disease) and associated predictors during pregnancy in patients with lupus with
urine protein <=1000 mg and serum creatinine <1.2 mg/dl at baseline; 373 patients
(52% ethnic/racial minorities) enrolled between 2003 and 2012 were prospectively
followed in the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid
Syndrome and Systemic Lupus Erythematosus Study. Active nephritis was defined by
proteinuria increase of >500 mg and/or red blood cell casts. RESULTS: Of 118
patients with previous kidney disease, 13 renal flares (11%) occurred (seven of
89 in complete remission and six of 29 in partial remission) compared with four
with de novo kidney involvement (2%) in 255 patients without past kidney disease
(P<0.001). Active nephritis was not associated with ethnicity, race, age,
creatinine, BP, or antihypertensive and other medications. In multivariable
logistic regression analyses, patients with past kidney disease in complete or
partial remission more often experienced active nephritis (adjusted odds ratio,
6.88; 95% confidence interval, 1.84 to 25.71; P=0.004 and adjusted odds ratio,
20.98; 95% confidence interval, 4.69 to 93.98; P<0.001, respectively) than those
without past kidney disease. Low C4 was associated with renal flares/de novo
disease (adjusted odds ratio, 5.59; 95% confidence interval, 1.64 to 19.13;
P<0.01) but not low C3 or positive anti-dsDNA alone. CONCLUSIONS: De novo kidney
involvement in SLE, even in ethnic/racial minorities, is uncommon during
pregnancy. Past kidney disease and low C4 at baseline independently associate
with higher risk of developing active nephritis. Antibodies to dsDNA alone should
not raise concern, even in patients with past kidney disease, if in remission.
PMID- 28400423
TI - Talus fracture in a 4-year-old child.
AB - Fracture of the talus is uncommon in childhood. We report a case of talar neck
fracture that occurred in a 4-year-old girl. We present the radiological
findings, the orthopaedic follow-up and the clinical outcome.
PMID- 28400424
TI - Increased taxon sampling reveals thousands of hidden orthologs in flatworms.
AB - Gains and losses shape the gene complement of animal lineages and are a
fundamental aspect of genomic evolution. Acquiring a comprehensive view of the
evolution of gene repertoires is limited by the intrinsic limitations of common
sequence similarity searches and available databases. Thus, a subset of the gene
complement of an organism consists of hidden orthologs, i.e., those with no
apparent homology to sequenced animal lineages-mistakenly considered new genes
but actually representing rapidly evolving orthologs or undetected paralogs.
Here, we describe Leapfrog, a simple automated BLAST pipeline that leverages
increased taxon sampling to overcome long evolutionary distances and identify
putative hidden orthologs in large transcriptomic databases by transitive
homology. As a case study, we used 35 transcriptomes of 29 flatworm lineages to
recover 3427 putative hidden orthologs, some unidentified by OrthoFinder and
HaMStR, two common orthogroup inference algorithms. Unexpectedly, we do not
observe a correlation between the number of putative hidden orthologs in a
lineage and its "average" evolutionary rate. Hidden orthologs do not show unusual
sequence composition biases that might account for systematic errors in sequence
similarity searches. Instead, gene duplication with divergence of one paralog and
weak positive selection appear to underlie hidden orthology in Platyhelminthes.
By using Leapfrog, we identify key centrosome-related genes and homeodomain
classes previously reported as absent in free-living flatworms, e.g., planarians.
Altogether, our findings demonstrate that hidden orthologs comprise a significant
proportion of the gene repertoire in flatworms, qualifying the impact of gene
losses and gains in gene complement evolution.
PMID- 28400425
TI - The logic of transcriptional regulator recruitment architecture at cis-regulatory
modules controlling liver functions.
AB - Control of gene transcription relies on concomitant regulation by multiple
transcriptional regulators (TRs). However, how recruitment of a myriad of TRs is
orchestrated at cis-regulatory modules (CRMs) to account for coregulation of
specific biological pathways is only partially understood. Here, we have used
mouse liver CRMs involved in regulatory activities of the hepatic TR, NR1H4 (FXR;
farnesoid X receptor), as our model system to tackle this question. Using
integrative cistromic, epigenomic, transcriptomic, and interactomic analyses, we
reveal a logical organization where trans-regulatory modules (TRMs), which
consist of subsets of preferentially and coordinately corecruited TRs, assemble
into hierarchical combinations at hepatic CRMs. Different combinations of TRMs
add to a core TRM, broadly found across the whole landscape of CRMs, to
discriminate promoters from enhancers. These combinations also specify distinct
sets of CRM differentially organized along the genome and involved in regulation
of either housekeeping/cellular maintenance genes or liver-specific functions. In
addition to these TRMs which we define as obligatory, we show that facultative
TRMs, such as one comprising core circadian TRs, are further recruited to
selective subsets of CRMs to modulate their activities. TRMs transcend TR
classification into ubiquitous versus liver-identity factors, as well as TR
grouping into functional families. Hence, hierarchical superimpositions of
obligatory and facultative TRMs bring about independent transcriptional
regulatory inputs defining different sets of CRMs with logical connection to
regulation of specific gene sets and biological pathways. Altogether, our study
reveals novel principles of concerted transcriptional regulation by multiple TRs
at CRMs.
PMID- 28400426
TI - A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy
for High-Risk Bladder Cancer Patients.
AB - Purpose: Hypoxia modification improves overall survival in muscle-invasive
bladder cancer patients who undergo radiotherapy. There is evidence that hypoxic
tumors benefit most from hypoxia modification. The study aimed to identify or
derive a hypoxia gene signature that predicts benefit from hypoxia-modifying
treatment in bladder cancer.Experimental Design: Published hypoxia signatures
were tested and a new one derived by analyzing bladder cancer transcriptomic data
from public databases. Tumor samples were available from the BCON phase III
randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON).
Gene expression data were generated for 151 tumors using Affymetrix Human 1.0
Exon ST arrays and used for independent validation.Results: A 24-gene signature
was derived, which was prognostic in four of six independent surgical cohorts (n
= 679; meta HR, 2.32; 95% CI, 1.73-3.12; P < 0.0001). The signature was also
prognostic in BCON patients receiving radiotherapy alone (n = 75; HR for local
relapse-free survival, 2.37; 95% CI, 1.26-4.47; P = 0.0076). The signature
predicted benefit from CON (n = 76; HR, 0.47; 95% CI, 0.26-0.86; P = 0.015).
Prognostic significance (P = 0.017) and predictive significance (P = 0.058)
remained after adjusting for clinicopathologic variables. A test for interaction
between hypoxia status and treatment arms was significant (P =
0.0094).Conclusions: A 24-gene hypoxia signature has strong and independent
prognostic and predictive value for muscle-invasive bladder cancer patients. The
signature can aid identification of patients likely to benefit from the addition
of carbogen and nicotinamide to radiotherapy. Clin Cancer Res; 23(16); 4761-8.
(c)2017 AACR.
PMID- 28400427
TI - Circulating DNA Demonstrates Convergent Evolution and Common Resistance
Mechanisms during Treatment of Colorectal Cancer.
AB - Purpose: Liquid biopsies allow the tracking of clonal dynamics and detection of
mutations during treatment.Experimental Design: We evaluated under blinded
conditions the ability of cell-free DNA (cfDNA) to detect RAS/BRAF mutations in
the plasma of 42 metastatic colorectal cancer patients treated on a phase Ib/II
trial of FOLFOX and dasatinib, with or without cetuximab.Results: Prior to
treatment, sequencing of archival tissue detected mutations in 25 of 42 patients
(60%), while the cfDNA assay detected mutations in 37 of 42 patients (88%). Our
cfDNA assay detected mutations with allele frequencies as low as 0.01%. After
exposure to treatment, 41 of 42 patients (98%) had a cfDNA-detected RAS/BRAF
mutation. Of 21 patients followed with serial measurements who were RAS/BRAF
mutant at baseline, 11 (52%) showed additional point mutation following treatment
and 3 (14%) no longer had detectable levels of another mutant allele. Of RAS/BRAF
wild-type tumors at baseline, 4 of 5 (80%) showed additional point mutations.
cfDNA quantitative measurements from this study closely mirrored changes in CEA
and CT scan results, highlighting the importance of obtaining quantitative data
beyond the mere presence of a mutation.Conclusions: Our findings demonstrate the
development of new RAS/BRAF mutations in patients regardless of whether they had
preexisting mutations in the pathway, demonstrating a convergent evolutionary
pattern. Clin Cancer Res; 23(16); 4578-91. (c)2017 AACR.
PMID- 28400428
TI - Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease
Activity in Patients with Head and Neck Cancer.
AB - Purpose: Head and neck cancers (HNCs) often induce profound immunosuppression,
which contributes to disease progression and interferes with immune-based
therapies. Body fluids of patients with HNC are enriched in exosomes potentially
engaged in negative regulation of antitumor immune responses. The presence and
content of exosomes derived from plasma of patients with HNC are evaluated for
the ability to induce immune dysfunction and influence disease
activity.Experimental Design: Exosomes were isolated by size-exclusion
chromatography from plasma of 38 patients with HNC and 14 healthy donors.
Morphology, size, numbers, and protein and molecular contents of the recovered
exosomes were determined. Coculture assays were performed to measure exosome
mediated effects on functions of normal human lymphocyte subsets and natural
killer (NK) cells. The results were correlated with disease stage and
activity.Results: The presence, quantity, and molecular content of isolated,
plasma-derived exosomes discriminated patients with HNC with active disease (AD)
from those with no evident disease (NED) after oncologic therapies. Exosomes of
patients with AD were significantly more effective than exosomes of patients with
NED in inducing apoptosis of CD8+ T cells, suppression of CD4+ T-cell
proliferation, and upregulation of regulatory T-cell (Treg) suppressor functions
(all at P < 0.05). Exosomes of patients with AD also downregulated NKG2D
expression levels in NK cells.Conclusions: Exosomes in plasma of patients with
HNC carry immunosuppressive molecules and interfere with functions of immune
cells. Exosome-induced immune suppression correlates with disease activity in
HNC, suggesting that plasma exosomes could be useful as biomarkers of HNC
progression. Clin Cancer Res; 23(16); 4843-54. (c)2017 AACR.
PMID- 28400429
TI - Genomic Analysis of Thymic Epithelial Tumors Identifies Novel Subtypes Associated
with Distinct Clinical Features.
AB - Purpose: To reconcile the heterogeneity of thymic epithelial tumors (TET) and
gain deeper understanding of the molecular determinants of TETs, we set out to
establish a clinically relevant molecular classification system for these
tumors.Experimental Design: Molecular subgrouping of TETs was performed in 120
patients from The Cancer Genome Atlas using a multidimensional approach
incorporating analyses of DNA mutations, mRNA expression, and somatic copy number
alterations (SCNA), and validated in two independent cohorts.Results: Four
distinct molecular subtypes of TETs were identified. The most commonly identified
gene mutation was a missense mutation in General Transcription Factor II-I (GTF2I
group), which was present in 38% of patients. The next group was identified by
unsupervised mRNA clustering of GTF2I wild-type tumors and represented TETs
enriched in expression of genes associated with T-cell signaling (TS group; 33%).
The remaining two groups were distinguished by their degree of chromosomal
stability (CS group; 8%) or instability (CIN group; 21%) based upon SCNA
analyses. Disease-free survival and overall survival were favorable in the GTF2I
group and unfavorable in the CIN group. These molecular subgroups were associated
with TET histology and clinical features including disease-free survival.
Finally, we demonstrate high expression of PD1 mRNA and correlation of PD1 and
CD8A in the TS subgroup.Conclusions: Molecular subtyping of TETs is associated
with disease-free and overall survival. Classification of TETs by a molecular
framework could aid in the refinement of staging and in the discovery and
development of rational treatment options for patients with TETs. Clin Cancer
Res; 23(16); 4855-64. (c)2017 AACR.
PMID- 28400430
TI - BMI and All-Cause Mortality in Normoglycemia, Impaired Fasting Glucose, Newly
Diagnosed Diabetes, and Prevalent Diabetes: A Cohort Study.
AB - OBJECTIVE: This study examined associations between BMI and mortality in
individuals with normoglycemia, impaired fasting glucose (IFG), newly diagnosed
diabetes, and prevalent diabetes and identified BMI ranges associated with the
lowest mortality in each group. RESEARCH DESIGN AND METHODS: A total of
12,815,006 adults were prospectively monitored until 2013. Diabetes status was
defined as follows: normoglycemia (fasting glucose <100 mg/dL), IFG (100-125
mg/dL), newly diagnosed diabetes (>=126 mg/dL), and prevalent diabetes (self
reported). BMI (kg/m2) was measured. Cox proportional hazards model hazard ratios
were calculated after adjusting for confounders. RESULTS: During a mean follow-up
period of 10.5 years, 454,546 men and 239,877 women died. U-shaped associations
were observed regardless of diabetes status, sex, age, and smoking history.
Optimal BMI (kg/m2) for the lowest mortality by group was 23.5-27.9
(normoglycemia), 25-27.9 (IFG), 25-29.4 (newly diagnosed diabetes), and 26.5-29.4
(prevalent diabetes). Higher optimal BMI by worsening diabetes status was more
prominent in younger ages, especially in women. The relationship between
worsening diabetes status and higher mortality was stronger with lower BMI,
especially at younger ages. Given the same BMI, people with prevalent diabetes
had higher mortality compared with those with newly diagnosed diabetes, and this
was more striking in women than men. CONCLUSIONS: U-curve relationships existed
regardless of diabetes status. Optimal BMI for lowest mortality became gradually
higher with worsening diabetes for each sex and each age-group.
PMID- 28400431
TI - Methodological issues limit interpretation of negative effects of satellite cell
depletion on adult muscle hypertrophy.
PMID- 28400432
TI - An apparent lack of effect of satellite cell depletion on hypertrophy could be
due to methodological limitations. Response to 'Methodological issues limit
interpretation of negative effects of satellite cell depletion on adult muscle
hypertrophy'.
PMID- 28400436
TI - Correction: An anterior signaling center patterns and sizes the anterior
neuroectoderm of the sea urchin embryo.
PMID- 28400435
TI - Correction: Neural specificity of the RNA-binding protein Elav is achieved by
post-transcriptional repression in non-neural tissues.
PMID- 28400433
TI - Stem cell therapies for retinal diseases: recapitulating development to replace
degenerated cells.
AB - Retinal degenerative diseases are the leading causes of blindness worldwide.
Replacing lost retinal cells via stem cell-based therapies is an exciting,
rapidly advancing area of translational research that has already entered the
clinic. Here, we review the status of these clinical efforts for several
significant retinal diseases, describe the challenges involved and discuss how
basic developmental studies have contributed to and are needed to advance
clinical goals.
PMID- 28400437
TI - A new niche for human HSCs.
PMID- 28400438
TI - How the stomach gets its curve.
PMID- 28400434
TI - Prostate organogenesis: tissue induction, hormonal regulation and cell type
specification.
AB - Prostate organogenesis is a complex process that is primarily mediated by the
presence of androgens and subsequent mesenchyme-epithelial interactions. The
investigation of prostate development is partly driven by its potential relevance
to prostate cancer, in particular the apparent re-awakening of key developmental
programs that occur during tumorigenesis. However, our current knowledge of the
mechanisms that drive prostate organogenesis is far from complete. Here, we
provide a comprehensive overview of prostate development, focusing on recent
findings regarding sexual dimorphism, bud induction, branching morphogenesis and
cellular differentiation.
PMID- 28400439
TI - Liverworts breathe easy.
PMID- 28400440
TI - Specialised fibroblasts maintain the nipple epidermis.
PMID- 28400442
TI - Peripherin diverts ciliary ectosome release to photoreceptor disc morphogenesis.
AB - Formation of membrane discs in photoreceptor cells requires evagination of its
ciliary plasma membrane by an unknown molecular mechanism. Salinas et al. (2017.
J. Cell Biol. https://doi.org/10.1083/jcb.201608081) show that peripherin (also
known as peripherin-2 or peripherin-2/rds) diverts membrane traffic to
photoreceptor disc formation by inhibiting ectosome release from the cilium.
PMID- 28400441
TI - Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific
Stardust isoforms.
AB - Crumbs (Crb) is a conserved determinant of apical membrane identity that
regulates epithelial morphogenesis in many developmental contexts. In this study,
we identify the Crb complex protein Stardust (Sdt) as a target of the E3
ubiquitin ligase Neuralized (Neur) in Drosophila melanogaster Neur interacts with
and down-regulates specific Sdt isoforms containing a Neur binding motif (NBM).
Using a CRISPR (clustered regularly interspaced short palindromic repeats)
induced deletion of the NBM-encoding exon, we found that Sdt is a key Neur target
and that Neur acts via Sdt to down-regulate Crb. We further show that Neur
promotes the endocytosis of Crb via the NBM-containing isoforms of Sdt. Although
the regulation of Crb by Neur is not strictly essential, it contributes to
epithelium remodeling in the posterior midgut and thereby facilitates the trans
epithelial migration of the primordial germ cells in early embryos. Thus, our
study uncovers a novel regulatory mechanism for the developmental control of Crb
mediated morphogenesis.
PMID- 28400443
TI - Plastin increases cortical connectivity to facilitate robust polarization and
timely cytokinesis.
AB - The cell cortex is essential to maintain animal cell shape, and contractile
forces generated within it by nonmuscle myosin II (NMY-2) drive cellular
morphogenetic processes such as cytokinesis. The role of actin cross-linking
proteins in cortical dynamics is still incompletely understood. Here, we show
that the evolutionarily conserved actin bundling/cross-linking protein plastin is
instrumental for the generation of potent cortical actomyosin contractility in
the Caenorhabditis elegans zygote. PLST-1 was enriched in contractile structures
and was required for effective coalescence of NMY-2 filaments into large
contractile foci and for long-range coordinated contractility in the cortex. In
the absence of PLST-1, polarization was compromised, cytokinesis was delayed or
failed, and 50% of embryos died during development. Moreover, mathematical
modeling showed that an optimal amount of bundling agents enhanced the ability of
a network to contract. We propose that by increasing the connectivity of the F
actin meshwork, plastin enables the cortex to generate stronger and more
coordinated forces to accomplish cellular morphogenesis.
PMID- 28400448
TI - Partnering with patients: how did you involve patients in your research?
PMID- 28400444
TI - Shaping proteostasis at the cellular, tissue, and organismal level.
AB - The proteostasis network (PN) regulates protein synthesis, folding, transport,
and degradation to maintain proteome integrity and limit the accumulation of
protein aggregates, a hallmark of aging and degenerative diseases. In
multicellular organisms, the PN is regulated at the cellular, tissue, and
systemic level to ensure organismal health and longevity. Here we review these
three layers of PN regulation and examine how they collectively maintain cellular
homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis
across tissues. A precise understanding of these layers of control has important
implications for organismal health and could offer new therapeutic approaches for
neurodegenerative diseases and other chronic disorders related to PN dysfunction.
PMID- 28400445
TI - MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle
Atrophy.
AB - Muscle atrophy is a frequent complication of CKD, and exercise can attenuate the
process. This study investigated the role of microRNA-23a (miR-23a) and miR-27a
in the regulation of muscle mass in mice with CKD. These miRs are located in a
gene cluster that is regulated by the transcription factor NFAT. CKD mice
expressed less miR-23a in muscle than controls, and resistance exercise (muscle
overload) increased the levels of miR-23a and miR-27a in CKD mice. Injection of
an adeno-associated virus encoding the miR-23a/27a/24-2 precursor RNA into the
tibialis anterior muscles of normal and CKD mice led to increases in mature miR
23a and miR-27a but not miR-24-2 in the muscles of both cohorts. Overexpression
of miR-23a/miR-27a in CKD mice attenuated muscle loss, improved grip strength,
increased the phosphorylation of Akt and FoxO1, and decreased the activation of
phosphatase and tensin homolog (PTEN) and FoxO1 and the expression of
TRIM63/MuRF1 and FBXO32/atrogin-1 proteins. Provision of miR-23a/miR-27a also
reduced myostatin expression and downstream SMAD-2/3 signaling, decreased
activation of caspase-3 and -7, and increased the expression of markers of muscle
regeneration. Lastly, in silico miR target analysis and luciferase reporter
assays in primary satellite cells identified PTEN and caspase-7 as targets of miR
23a and FoxO1 as a target of miR-27a in muscle. These findings provide new
insights about the roles of the miR-23a/27a-24-2 cluster in CKD-induced muscle
atrophy in mice and suggest a mechanism by which exercise helps to maintain
muscle mass.
PMID- 28400449
TI - Erratum: 'Reforming abortion services in the UK: less hypocrisy, more
acknowledgment of complexity'.
PMID- 28400450
TI - Challenges to understanding the reproductive health needs of women forcibly
displaced by the Syrian conflict.
PMID- 28400446
TI - Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated
Vasculitis.
AB - Alternative C activation is involved in the pathogenesis of ANCA-associated
vasculitis. However, glucocorticoids used as treatment contribute to the
morbidity and mortality of vasculitis. We determined whether avacopan (CCX168),
an orally administered, selective C5a receptor inhibitor, could replace oral
glucocorticoids without compromising efficacy. In this randomized, placebo
controlled trial, adults with newly diagnosed or relapsing vasculitis received
placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg,
twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg,
twice daily) without prednisone. All patients received cyclophosphamide or
rituximab. The primary efficacy measure was the proportion of patients achieving
a >=50% reduction in Birmingham Vasculitis Activity Score by week 12 and no
worsening in any body system. We enrolled 67 patients, 23 in the control and 22
in each of the avacopan groups. Clinical response at week 12 was achieved in 14
of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus
reduced-dose prednisone group (difference from control 16.4%; two-sided 90%
confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21
(81.0%) patients in the avacopan without prednisone group (difference from
control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for
noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19
of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21
of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a
receptor inhibition with avacopan was effective in replacing high-dose
glucocorticoids in treating vasculitis.
PMID- 28400451
TI - Shattering the myths of private practice.
PMID- 28400452
TI - Comment on 'Postpartum contraception: a missed opportunity to prevent unintended
pregnancy and short inter-pregnancy intervals'.
PMID- 28400453
TI - Authors' response to comment on 'Postpartum contraception: a missed opportunity
to prevent unintended pregnancy and short inter-pregnancy intervals'.
PMID- 28400454
TI - Rosamund Snow: researcher and campaigner for patients' involvement in healthcare:
(born 1971, died by suicide on 2 February 2017).
PMID- 28400455
TI - Venus.
PMID- 28400456
TI - Diverging effects of diabetes mellitus in patients with peripheral artery disease
and abdominal aortic aneurysm and the role of advanced glycation end-products:
ARTERY study - protocol for a multicentre cross-sectional study.
AB - INTRODUCTION: Diabetes mellitus is a well-defined risk factor for peripheral
artery disease (PAD), but protects against the development and growth of
abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial
stiffening and peripheral arterial media sclerosis. Advanced glycation end
products (AGEs) are increased in diabetes mellitus and cardiovascular disease.
AGEs are known to form cross-links between proteins and are associated with
arterial stiffness. Whether AGEs contribute to the protective effects of diabetes
mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end
pRoducts in patients with peripheral arTery disEase and abdominal aoRtic
aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects
of diabetes mellitus on AAA and PAD. METHODS AND ANALYSIS: This cross-sectional
multicentre study will compare the amount, type and location of AGEs in the
arterial wall in a total of 120 patients with AAA or PAD with and without
diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular
parameters, including pulse wave velocity, will be measured to evaluate the
association between arterial stiffness and AGEs. Finally, AGEs will be measured
in serum, urine, and assessed in skin with skin autofluorescence using the AGE
Reader. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics
committees of University Medical Center Groningen, Martini Hospital and Medisch
Spectrum Twente, the Netherlands. Study results will be disseminated through peer
reviewed journals and scientific events. TRIAL REGISTRATION NUMBER:
trialregister.nl NTR 5363.
PMID- 28400457
TI - Emergency nurse disaster preparedness during mass gatherings: a cross-sectional
survey of emergency nurses' perceptions in hospitals in Mecca, Saudi Arabia.
AB - OBJECTIVES: To assess hospital emergency nurses' self-reported knowledge, role
awareness and skills in disaster response with respect to the Hajj mass gathering
in Mecca. DESIGN: Cross-sectional online survey with primary data collection and
non-probabilistic purposive sample conducted in late 2014. SETTING: All 4 public
hospitals in Mecca, Saudi Arabia. PARTICIPANTS: 106 registered nurses in hospital
emergency departments. MAIN OUTCOME MEASURE: Awareness, knowledge, skills and
perceptions of emergency nurses in Mecca with regard to mass gathering disaster
preparedness. RESULTS: Although emergency nurses' clinical role awareness in
disaster response was reported to be high, nurses reported limited knowledge and
awareness of the wider emergency and disaster preparedness plans, including key
elements of their hospital strategies for managing a mass gathering disaster.
Over half of the emergency nurses in Mecca's public hospitals had not thoroughly
read the plan, and almost 1 in 10 were not even aware of its existence. Emergency
nurses reported seeing their main role as providing timely general clinical
assessment and care; however, fewer emergency nurses saw their role as providing
surveillance, prevention, leadership or psychological care in a mass gathering
disaster, despite all these broader roles being described in the hospitals'
emergency disaster response plans. Emergency nurses' responses to topics where
there are often misconceptions on appropriate disaster management indicated a
significant knowledge deficit with only 1 in 3 nurses at best or 1 in 6 at worst
giving correct answers. Respondents identified 3 key training initiatives as
opportunities to further develop their professional skills in this area: (1)
hospital education sessions, (2) the Emergency Management Saudi Course, (3)
bespoke short courses in disaster management. CONCLUSIONS: Recommendations are
suggested to help enhance clinical and educational efforts in disaster
preparedness.
PMID- 28400458
TI - What drives the prescribing of growth hormone preparations in England? Prices
versus patient preferences.
AB - OBJECTIVE: The patent expiry of a number of biological medicines and the advent
of biosimilars raised the expectations of healthcare commissioners that
biosimilars would reduce the high cost of these medicines and produce potential
savings to the NHS. We aimed to examine the prescribing pattern of different
growth hormone preparations (ready to use and reconstitution requiring) in
primary and secondary care in England to determine relative rates of decrease or
increase and identify the possible factors influencing prescribing following the
introduction of biosimilar growth hormone in 2008. DESIGN: Longitudinal
observational study. SETTING AND DATA SOURCES: Primary care prescribing cost and
volume data was derived from the NHS business services authority website, and for
secondary care from the DEFINE database, between April 2011 and December 2015.
OUTCOMES: Quarterly prescribing analysis to examine trends and measure the
relationship between usage and price. RESULTS: Expenditure and usage of growth
hormone in primary care decreased by 17.91% and 7.29%, respectively, whereas
expenditure and usage in secondary care increased by 68.41% and 100%,
respectively, between April 2011 and December 2015. The usage of reconstitution
requiring products significantly declined in primary care (R2=0.9292) and
slightly increased in use in secondary care (R2=0.139). In contrast, the usage of
ready-to-use products significantly increased in use in primary (R2=0.7526) and
secondary care (R2=0.9633), respectively. Weak or no correlation existed between
the usage and price of growth hormone preparations in primary and secondary care.
CONCLUSIONS: The price of growth hormone products was not the key factor
influencing the prescribing of the biological medicines. The main driver for
specific product selection was the ease of use and the number of steps in dose
preparation. Prescribers appear to be taking into account patient preferences
rather than cost in their prescribing decisions.
PMID- 28400459
TI - Investigating the relationship between precocious puberty and obesity: a cross
sectional study in Shanghai, China.
AB - OBJECTIVES: Obesity is reported to be closely relevant to early sexual
development but the relationship between sexual precocity and obesity or central
obesity is still inconsistent, especially in boys. We aimed to investigate the
relationship between precocious puberty and obesity as well as central obesity.
DESIGN: A large population-based cross-sectional study using multistage,
stratified cluster random sampling. SETTING: Data from the Shanghai Children's
Health, Education and Lifestyle Evaluation (SCHEDULE) study in June 2014.
PARTICIPANTS: 17 620 Chinese children aged 6-12 years. PRIMARY AND SECONDARY
OUTCOME MEASURES: Obesity was defined by WHO Child Growth Standards. Central
obesity was defined by sex-specific waist-to-height ratio (WHtR) cut-offs (WHtR
>=0.48 for boys, WHtR >=0.46 for girls). Precocious puberty was identified by
Tanner stage of breast, pubic hair and testicle development. A chi2 test was
performed to compare rates. Odds ratios (ORs) with 95% confidence intervals (CIs)
were calculated to assess the association between precocious puberty and general
obesity and central obesity. Probit analysis was used for estimating the median
age at entry into Tanner stage 2 or greater for breast, pubic hair and testicle
development. Linear regression was utilised to compare the effects of WHtR and
body mass index (BMI) on sex development indicators. RESULTS: 25.98% and 38.58%
of boys with precocious puberty were respectively accompanied by obesity
(OR=2.15, 95% CI=1.31 to 3.50) or central obesity (OR=2.10, 95% CI=1.46 to 3.03);
meanwhile, 13.86% and 29.42% of girls with precocious puberty were respectively
accompanied by obesity (OR=9.00, 95% CI=5.60 to 14.46) or central obesity
(OR=5.40, 95% CI=4.10 to 7.12). The median ages of breast, pubic hair and
testicle development decreased with BMI increase and median ages of thelarche and
testicular development rather than pubarche were earlier in children with central
obesity. CONCLUSIONS: Earlier pubertal development was positively associated with
obesity and central obesity in Chinese children.
PMID- 28400460
TI - Direct costs of osteoporosis-related hip fractures: protocol for a cross
sectional analysis of a national database.
AB - INTRODUCTION: It is estimated that Iran accounted for about 1% of hip fracture
burden of the world in 2007, but these data are based on incomplete evidence. As
the country's population is ageing, it is expected that a dramatic rise in hip
fracture incidence will result. There is no single national study that accurately
estimates the incidence of all hip fractures in the country or identifies the
direct costs for affected patients. To help fill this gap, the current study has
been designed to determine the incidence of hip fracture associated with
osteoporosis in the Iranian population and to assess the direct costs involved.
METHODS AND ANALYSIS: This is a cross-sectional analysis of 2 years of hospital
admissions due to hip fracture in Iran from October 2014 to October 2016 using an
electronic health record called SEPAS. SEPAS is a nationwide health information
system established by Information Technology (IT) and the Statistics Department
of the Ministry of Health. SEPAS has recorded more than 8.5 million inpatient
hospitalizations since October 2014. Our study will identify reported hip
fracture data in SEPAS among admitted adult hospital patients aged >=50 in Iran.
International Classification of Diseases ICD-9 and 10 will be used as diagnostic
codes. Study factors are demographic data, types of fracture, types of treatment,
duration of admission, early complications, in-hospital mortality and direct cost
of fracture treatment. The accuracy of the SEPAS fracture data will be
ascertained through a pilot study that compares the SEPAS data with the data
directly extracted from medical records of the Shariati Hospital in Tehran during
the study period. ETHICS AND DISSEMINATION: The study protocol was approved by
the Ethics Committee of the National Institute for Medical Research Development
of Iran. Dissemination plans include academic publications, conference
presentations and social media.
PMID- 28400463
TI - Letter by Fournier et al Regarding Article, "Functional Assessment of Coronary
Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation:
Influence of Pressure Overload on the Evaluation of Lesions Severity".
PMID- 28400462
TI - Saline-Induced Coronary Hyperemia: Mechanisms and Effects on Left Ventricular
Function.
AB - BACKGROUND: During thermodilution-based assessment of volumetric coronary blood
flow, we observed that intracoronary infusion of saline increased coronary flow.
This study aims to quantify the extent and unravel the mechanisms of saline
induced hyperemia. METHODS AND RESULTS: Thirty-three patients were studied; in 24
patients, intracoronary Doppler flow velocity measurements were performed at
rest, after intracoronary adenosine, and during increasing infusion rates of
saline at room temperature through a dedicated catheter with 4 lateral side
holes. In 9 patients, global longitudinal strain and flow propagation velocity
were assessed by transthoracic echocardiography during a prolonged intracoronary
saline infusion. Taking adenosine-induced maximal hyperemia as reference,
intracoronary infusion of saline at rates of 5, 10, 15, and 20 mL/min induced 6%,
46%, 111%, and 112% of maximal hyperemia, respectively. There was a close
agreement of maximal saline- and adenosine-induced coronary flow reserve
(intraclass correlation coefficient, 0.922; P<0.001). The same infusion rates
given through 1 end hole (n=6) or in the contralateral artery (n=6) did not
induce a significant increase in flow velocity. Intracoronary saline given on top
of an intravenous infusion of adenosine did not further increase flow.
Intracoronary saline infusion did not affect blood pressure, systolic, or
diastolic left ventricular function. Heart rate decreased by 15% during saline
infusion (P=0.021). CONCLUSIONS: Intracoronary infusion of saline at room
temperature through a dedicated catheter for coronary thermodilution induces
steady-state maximal hyperemia at a flow rate >=15 mL/min. These findings open
new possibilities to measure maximal absolute coronary blood flow and minimal
microcirculatory resistance.
PMID- 28400461
TI - Matched Comparison of Self-Expanding Transcatheter Heart Valves for the Treatment
of Failed Aortic Surgical Bioprosthesis: Insights From the Valve-in-Valve
International Data Registry (VIVID).
AB - BACKGROUND: Transcatheter valve-in-valve implantation is an established therapy
for high-risk patients with failed surgical aortic bioprosthesis. There are
limited data comparing outcomes of valve-in-valve implantation using different
transcatheter heart valves (THV). METHODS AND RESULTS: Patients included in the
Valve-in-Valve International Data registry (VIVID) and treated with self
expanding THV devices were analyzed using centralized core laboratory blinded to
clinical events. St. Jude Medical Portico versus Medtronic CoreValve were
compared in a 1:2 fashion after propensity score matching. A total of 162
patients, Portico- (n=54) and CoreValve- (n=108) based valve-in-valve procedures
comprised the study population with no significant difference in baseline
characteristics (age, 79+/-8.2 years; 60% women; mean STS [Society of Thoracic
Surgery] score 8.1+/-5.5%). Postimplantation, CoreValve was associated with a
larger effective orifice area (1.67 versus 1.31 cm2; P=0.001), lower mean
gradient (14+/-7.5 versus 17+/-7.5 mm Hg; P=0.02), and lower core laboratory
adjudicated moderate-to-severe aortic insufficiency (4.2% versus 13.7%; P=0.04),
compared with Portico. Procedural complications including THV malpositioning,
second THV requirement, or coronary obstruction were not significantly different
between the 2 groups. Survival and stroke rates at 30 days were similar, but
overall mortality at 1 year was higher among patients treated with Portico
compared with CoreValve (22.6% versus 9.1%; P=0.03). CONCLUSIONS: In this first
matched comparison of THVs for valve-in-valve implantations, Portico and
CoreValve demonstrated differences in postprocedural hemodynamics and long-term
clinical outcomes. Although this could be related to THV design characteristics,
the impact of other procedural factors cannot be excluded and require further
evaluation.
PMID- 28400464
TI - Utilisation of radiology rotations in ACGME-accredited general surgery
programmes.
AB - BACKGROUND: General surgery (GS) residents are often required to provide
immediate preliminary interpretations of radiological images, especially in
critical situations. It is unclear whether residents in Accreditation Council for
Graduate Medical Education-accredited GS programmes receive sufficient
radiological training to deliver adequate patient care. OBJECTIVES: Determine the
utilisation of radiology rotations (RR) during GS residency. METHODS: Between
February and March 2015, a pilot voluntary 19-item survey was electronically
distributed to GS programme directors (PDs) regarding the availability and value
of a RR during GS training. RESULTS: A total of 234 PDs received the
questionnaire and the response rate was 36.8% (n=86). Sixty-five (77.4%) PDs
expected their trainees to interpret imaging studies in the acute setting;
however, only 8.3% of programmes had a dedicated RR. RRs are more prevalent among
community-based than university-based programmes (71.4% vs 27.9% p=0.003). The
implementation of a RR may be limited due to insufficient number of GS residents
in the department (p=0.002). 75.4% of PDs expect GS residents to confirm their
findings with a radiologist. In those programmes with RR, most PDs (85.7%)
believed that a dedicated rotation improved GS residents' understanding of
radiological imaging. CONCLUSION: The majority of PDs are currently not confident
that GS residents are capable of interpreting radiological imaging independently;
however, the implementation of a mandatory RR in GS residency curriculum yet
seems to be controversial. Given the expectation of PDs and the continued need to
improve patient care, the integration of a dedicated RR in GS training should be
encouraged.
PMID- 28400465
TI - Hypercholesterolemia impairs oxytocin-induced uterine contractility in late
pregnant mouse.
AB - High cholesterol is known to negatively affect uterine contractility in ex vivo
conditions. The aim of the present study was to reveal the effect of in vivo
hypercholesterolemia on spontaneous and oxytocin-induced uterine contractility in
late pregnant mouse uterus. Female Swiss albino mice were fed with high
cholesterol (HC) diet (0.5% sodium cholate, 1.25% cholesterol and 15% fat) for 6
weeks and then throughout the gestation period after mating. On day 19 of
gestation, serum cholesterol level was increased more than 3-fold while
triglycerides level was reduced in HC diet-fed animals as compared to control
animals fed with a standard diet. In tension experiments, neither the mean
integral tension of spontaneous contractility nor the response to CaCl2 in high
K+-depolarized tissues was altered, but the oxytocin-induced concentration
dependent contractile response in uterine strips was attenuated in
hypercholesterolemic mice as compared to control. Similarly, hypercholesterolemia
dampened concentration-dependent uterine contractions elicited by a GNAQ protein
activator, Pasteurella multocida toxin. However, it had no effect on endogenous
oxytocin level either in plasma or in uterine tissue. It also did not affect the
prostaglandin release in oxytocin-stimulated tissues. Western blot data showed a
significant increase in caveolin-1 and GRK6 proteins but decline in oxytocin
receptor, GNAQ and RHOA protein expressions in hypercholesterolemic mouse uterus.
The results of the present study suggest that hypercholesterolemia may attenuate
the uterotonic action of oxytocin in late pregnancy by causing downregulation of
oxytocin receptors and suppressing the signaling efficacy through GNAQ and RHOA
proteins.
PMID- 28400466
TI - Substance use among men who have sex with men: patterns, motivations, impacts and
intervention development need.
AB - OBJECTIVES: In this narrative review we illustrate the patterns of substance use
among gay, bisexual and other men who have sex with men (MSM), including
comparisons with heterosexual populations, subgroup analyses and settings of
substance use. We also consider explanations and motivations for substance use
and the impact of use on sexual health as well as wider health and well-being.
Finally, we consider the implications for the provision of MSM-tailored substance
use and harm reduction services. METHODS: We undertook a narrative review of
diverse literature across the fields of public health, psychology and sociology
to synthesise complex findings relating to the use and impacts of illicit drugs
and alcohol among MSM. Attempts were made to draw on literature from across the
globe, including all income settings. RESULTS: Global evidence relating to the
use of substances among MSM is limited due to the lack of disaggregation of data
by sexual orientation. While complicated by methodological diversity, most
research indicates a higher prevalence of illicit drug use among MSM compared
with their heterosexual counterparts, although the same is not necessarily true
of alcohol. A sense of belonging, coping with everyday problems and the
enhancement of pleasure, all feature in motivations for alcohol and drug use.
Global association studies document a link between substance use and sexual risk
behaviours, and event-level analyses suggest an especially strong association
with respect to alcohol. While there is some evidence that generic harm reduction
interventions can be effective among sexual minorities, these need to be tailored
to the social and cultural circumstances of MSM. CONCLUSIONS: Associations
between substance use and sexual risk behaviour among MSM have been well
documented, but the nature and pathway of these are poorly understood. A focus
largely on substance use and sexual risk may have served to mask the impact of
alcohol and drug use on the broader health and well-being of MSM.
PMID- 28400467
TI - Use of the GeneReader NGS System in a clinical pathology laboratory: a
comparative study.
AB - Despite its successful use in academic research, next-generation sequencing (NGS)
still represents many challenges for routine clinical adoption due to its
inherent complexity and specialised expertise typically required to set-up, test
and operate a complete workflow.This study aims to evaluate QIAGEN's newly
launched GeneReader NGS System solution in a pathology laboratory setting by
assessing the system's ease of use, sequencing accuracy and data reproducibility.
Our laboratory was able to implement the system and validate its performance
using clinical samples in direct comparison to an approved Sanger sequencing
platform and to an alternative in-house NGS technology. The QIAGEN workflow
focuses on clinically actionable hotspots maximising testing efficiency. Combined
with automated upstream sample processing and integrated downstream
bioinformatics, it offers a realistic solution for pathology laboratories with
limited prior experience in NGS technology.
PMID- 28400468
TI - The diagnostic value of hyperammonaemia induced by the non-ischaemic forearm
exercise test.
AB - AIMS: The non-ischaemic forearm exercise test (NIFET) is used as a diagnostic
tool for the screening of patients with exercise intolerance and for the
diagnosis of various metabolic muscle disorders. The production of lactate and
ammonia are generally analysed to guide the diagnosis. The aim of this
retrospective study was to determine the level of ammonia rise, which can be
suggestive of a muscle disease. METHODS: This retrospective study involved 1440
patients who underwent NIFET. The clinical files of the patients with
hyperammonaemia were methodically studied. Normal values were derived from 60
healthy controls. RESULTS: 110 patients with hyperammonaemia were detected. They
were classified as either having mild (between 94 and 141 umol/L) or severe (more
than 141 umol/L) hyperammonaemia. Their diagnosis was studied with respect to the
increase in lactate induced by the NIFET. CONCLUSIONS: Severe postexercise
hyperammonaemia, even in the presence of a normal lactate response, is strongly
suggestive of a muscle glycogen storage disease. Mild hyperammonaemia in the
absence of other abnormalities is most likely non-specific and not indicative of
a muscle disease.
PMID- 28400471
TI - A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial
sodium channel.
AB - Voltage-gated sodium channels (NaVs) are activated by transiting the voltage
sensor from the deactivated to the activated state. The crystal structures of
several bacterial NaVs have captured the voltage sensor module (VSM) in an
activated state, but structure of the deactivated voltage sensor remains elusive.
In this study, we sought to identify peptide toxins stabilizing the deactivated
VSM of bacterial NaVs. We screened fractions from several venoms and
characterized a cystine knot toxin called JZTx-27 from the venom of tarantula
Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic NaVs NsVBa
(nonselective voltage-gated Bacillus alcalophilus) and NaChBac (bacterial sodium
channel from Bacillus halodurans) (IC50 = 112 nM and 30 nM, respectively). JZTx
27 was more efficacious at weaker depolarizing voltages and significantly slowed
the activation but accelerated the deactivation of NsVBa, whereas the local
anesthetic drug lidocaine was shown to antagonize NsVBa without affecting channel
gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of NsVBa,
with F98 being the critical residue in determining toxin affinity. All
electrophysiological data and in silico analysis suggested that JZTx-27 trapped
VSM of NsVBa in one of the deactivated states. In mammalian NaVs, JZTx-27
preferably inhibited the inactivation of NaV1.5 by targeting the fourth
transmembrane domain. To our knowledge, this is the first report of peptide
antagonist for prokaryotic NaVs. More important, we proposed that JZTx-27
stabilized the NsVBa VSM in the deactivated state and may be used as a probe to
determine the structure of the deactivated VSM of NaVs.-Tang, C., Zhou, X.,
Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G.,
Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage
sensor of bacterial sodium channel.
PMID- 28400472
TI - Novel selective beta1-adrenoceptor antagonists for concomitant cardiovascular and
respiratory disease.
AB - beta-Blockers reduce mortality and improve symptoms in people with heart disease;
however, current clinically available beta-blockers have poor selectivity for the
cardiac beta1-adrenoceptor (AR) over the lung beta2-AR. Unwanted beta2-blockade
risks causing life-threatening bronchospasm and reduced efficacy of beta2-agonist
emergency rescue therapy. Thus, current life-prolonging beta-blockers are
contraindicated in patients with both heart disease and asthma. Here, we describe
NDD-713 and -825, novel highly beta1-selective neutral antagonists with good
pharmaceutical properties that can potentially overcome this limitation.
Radioligand binding studies and functional assays that use human receptors
expressed in Chinese hamster ovary cells demonstrate that NDD-713 and -825 have
nanomolar beta1-AR affinity >500-fold beta1-AR vs beta2-AR selectivity and no
agonism. Studies in conscious rats demonstrate that these antagonists are orally
bioavailable and cause pronounced beta1-mediated reduction of heart rate while
showing no effect on beta2-mediated hindquarters vasodilatation. These compounds
also have good disposition properties and show no adverse toxicologic effects.
They potentially offer a truly cardioselective beta-blocker therapy for the large
number of patients with heart and respiratory or peripheral vascular
comorbidities.-Baker, J. G., Gardiner, S. M., Woolard, J., Fromont, C., Jadhav,
G. P., Mistry, S. N., Thompson, K. S. J., Kellam, B., Hill, S. J., Fischer, P. M.
Novel selective beta1-adrenoceptor antagonists for concomitant cardiovascular and
respiratory disease.
PMID- 28400473
TI - TLR sensing of bacterial spore-associated RNA triggers host immune responses with
detrimental effects.
AB - The spores of pathogenic bacteria are involved in host entry and the initial
encounter with the host immune system. How bacterial spores interact with host
immunity, however, remains poorly understood. Here, we show that the spores of
Bacillus anthracis (BA), the etiologic agent of anthrax, possess an intrinsic
ability to induce host immune responses. This immunostimulatory activity is
attributable to high amounts of RNA present in the spore surface layer. RNA
sensing TLRs, TLR7, and TLR13 in mice and their human counterparts, are
responsible for detecting and triggering the host cell response to BA spores,
whereas TLR2 mediates the sensing of vegetative BA. BA spores, but not vegetative
BA, induce type I IFN (IFN-I) production. Although TLR signaling in itself
affords protection against BA, spore RNA-induced IFN-I signaling is disruptive to
BA clearance. Our study suggests a role for bacterial spore-associated RNA in
microbial pathogenesis and illustrates a little known aspect of interactions
between the host and spore-forming bacteria.
PMID- 28400474
TI - Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1.
AB - T helper type 17 cells (Th17 cells) are major contributors to many autoimmune
diseases. In this study, we demonstrate that the germinal center kinase family
member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell
differentiation. The suppressive effect of MINK1 on induction of Th17 cells is
mediated by the inhibition of SMAD2 activation through direct phosphorylation of
SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation
was strengthened in the animal model of experimental autoimmune encephalomyelitis
(EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N
acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and
exacerbates the severity of EAE. Thus, we have not only established MINK1 as a
critical regulator of Th17 cell differentiation, but also clarified that
accumulation of ROS may limit the generation of Th17 cells. The contribution of
MINK1 to ROS-regulated Th17 cell differentiation may suggest an important
mechanism for the development of autoimmune diseases influenced by antioxidant
dietary supplements.
PMID- 28400475
TI - An Ex Vivo Platform for the Prediction of Clinical Response in Multiple Myeloma.
AB - Multiple myeloma remains treatable but incurable. Despite a growing armamentarium
of effective agents, choice of therapy, especially in relapse, still relies
almost exclusively on clinical acumen. We have developed a system, Ex vivo
Mathematical Myeloma Advisor (EMMA), consisting of patient-specific mathematical
models parameterized by an ex vivo assay that reverse engineers the intensity and
heterogeneity of chemosensitivity of primary cells from multiple myeloma
patients, allowing us to predict clinical response to up to 31 drugs within 5
days after bone marrow biopsy. From a cohort of 52 multiple myeloma patients,
EMMA correctly classified 96% as responders/nonresponders and correctly
classified 79% according to International Myeloma Working Group stratification of
level of response. We also observed a significant correlation between predicted
and actual tumor burden measurements (Pearson r = 0.5658, P < 0.0001).
Preliminary estimates indicate that, among the patients enrolled in this study,
60% were treated with at least one ineffective agent from their therapy
combination regimen, whereas 30% would have responded better if treated with
another available drug or combination. Two in silico clinical trials with
experimental agents ricolinostat and venetoclax, in a cohort of 19 multiple
myeloma patient samples, yielded consistent results with recent phase I/II
trials, suggesting that EMMA is a feasible platform for estimating clinical
efficacy of drugs and inclusion criteria screening. This unique platform,
specifically designed to predict therapeutic response in multiple myeloma
patients within a clinically actionable time frame, has shown high predictive
accuracy in patients treated with combinations of different classes of drugs. The
accuracy, reproducibility, short turnaround time, and high-throughput potential
of this platform demonstrate EMMA's promise as a decision support system for
therapeutic management of multiple myeloma. Cancer Res; 77(12); 3336-51. (c)2017
AACR.
PMID- 28400476
TI - GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the
Brain Metastatic Microenvironment.
AB - The impact of altered amino acid metabolism on cancer progression is not fully
understood. We hypothesized that a metabolic transcriptome shift during
metastatic evolution is crucial for brain metastasis. Here, we report a powerful
impact in this setting caused by epigenetic upregulation of glutamate
decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic
pathway. In cell-based culture and brain metastasis models, we found that
downregulation of the DNA methyltransferase DNMT1 induced by the brain
microenvironment-derived clusterin resulted in decreased GAD1 promoter
methylation and subsequent upregulation of GAD1 expression in brain metastatic
tumor cells. In a system to dynamically visualize cellular metabolic responses
mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor
cells. Reducing GAD1 in metastatic cells by primary glia cell coculture abolished
the capacity of metastatic cells to utilize extracellular glutamine, leading to
cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic
or pharmacologic disruption of the GABA metabolic pathway decreased the incidence
of brain metastasis in vivo Taken together, our results show how epigenetic
changes in GAD1 expression alter local glutamate metabolism in the brain
metastatic microenvironment, contributing to a metabolic adaption that
facilitates metastasis outgrowth in that setting. Cancer Res; 77(11); 2844-56.
(c)2017 AACR.
PMID- 28400477
TI - IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition.
AB - The tumor microenvironment supplies proinflammatory cytokines favoring a
permissive milieu for cancer cell growth and invasive behavior. Here we show how
breast cancer progression is facilitated by IL4 secreted by adipose tissue and
estrogen receptor-positive and triple-negative breast cancer cell types. Blocking
autocrine and paracrine IL4 signaling with the IL4Ralpha antagonist IL4DM
compromised breast cancer cell proliferation, invasion, and tumor growth by
downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24- cancer
stem-like cells and elevated expression of the dual specificity phosphatase DUSP4
by inhibiting NF-kappaB. Enforced expression of DUSP4 drove conversion of
metastatic cells to nonmetastatic cells. Mechanistically, RNAi-mediated
attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like
properties, and spawned metastatic capacity. Targeting IL4 signaling sensitized
breast cancer cells to anticancer therapy and strengthened immune responses by
enhancing the number of IFNgamma-positive CTLs. Our results showed the role of
IL4 in promoting breast cancer aggressiveness and how its targeting may improve
the efficacy of current therapies. Cancer Res; 77(12); 3268-79. (c)2017 AACR.
PMID- 28400478
TI - Sixty seconds on . . . NHS jargon.
PMID- 28400479
TI - A Presurgical Study of Lecithin Formulation of Green Tea Extract in Women with
Early Breast Cancer.
AB - Epidemiologic data support an inverse association between green tea intake and
breast cancer risk. Greenselect Phytosome (GSP) is a lecithin formulation of a
caffeine-free green tea catechin extract. The purpose of the study was to
determine the tissue distribution of epigallocatechin-3-O-gallate (EGCG) and its
effect on cell proliferation and circulating biomarkers in breast cancer
patients. Twelve early breast cancer patients received GSP 300 mg, equivalent to
44.9 mg of EGCG, daily for 4 weeks prior to surgery. The EGCG levels were
measured before (free) and after (total) enzymatic hydrolysis by HPLC-MS/MS in
plasma, urine, breast cancer tissue, and surrounding normal breast tissue.
Fasting blood samples were taken at baseline, before the last administration, and
2 hours later. Repeated administration of GSP achieved levels of total EGCG
ranging from 17 to 121 ng/mL in plasma. Despite a high between-subject
variability, total EGCG was detectable in all tumor tissue samples collected up
to 8 ng/g. Median total EGCG concentration was higher in the tumor as compared
with the adjacent normal tissue (3.18 ng/g vs. 0 ng/g, P = 0.02). Free EGCG
concentrations ranged from 8 to 65.8 ng/mL in plasma (P between last
administration and 2 hours after <0.001). Free EGCG plasma levels showed a
significant positive correlation with the Ki-67 decrease in tumor tissue (P =
0.02). No change in any other biomarkers was noted, except for a slight increase
in testosterone levels after treatment. Oral GSP increases bioavailability of
EGCG, which is detectable in breast tumor tissue and is associated with
antiproliferative effects on breast cancer tissue. Cancer Prev Res; 10(6); 363-9.
(c)2017 AACR.
PMID- 28400480
TI - Combined Genetic Biomarkers and Betel Quid Chewing for Identifying High-Risk
Group for Oral Cancer Occurrence.
AB - We integrated genetic risk scores (GRS) and environmental factors for identifying
high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using
case-control study. A total of 447 patients diagnosed with OSCC and 580 unrelated
subjects were recruited from two medical centers in Taiwan. A multinomial
logistic regression model was conducted to access interaction between GRS and
betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC
occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes
that were significantly associated with OSCC occurrence. GRS was calculated by
the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently
associated with risk of OSCC after adjustment for age, the use of alcohol, BQ,
and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34-14.55].
The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence
with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70-575.73).
The synergy index was 16.58 (95% CI, 2.27-70.56), suggesting a positive additive
interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC)
were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and
specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be
valuable in identifying high-risk subjects. Early screening can allow the
clinician to provide the appropriate intervention and to reduce the OSCC
occurrence. Cancer Prev Res; 10(6); 355-62. (c)2017 AACR.
PMID- 28400481
TI - Progress in maternal and child health: how has South Asia fared?
PMID- 28400482
TI - Epigenetic programming of the neuroendocrine stress response by adult life
stress.
AB - The hypothalamic-pituitary-adrenal (HPA) axis is critically involved in the
neuroendocrine regulation of stress adaptation, and the restoration of
homeostasis following stress exposure. Dysregulation of this axis is associated
with stress-related pathologies like major depressive disorder, post-traumatic
stress disorder, panic disorder and chronic anxiety. It has long been understood
that stress during early life can have a significant lasting influence on the
development of the neuroendocrine system and its neural regulators, partially by
modifying epigenetic regulation of gene expression, with implications for health
and well-being in later life. Evidence is accumulating that epigenetic plasticity
also extends to adulthood, proposing it as a mechanism by which psychological
trauma later in life can long-lastingly affect HPA axis function, brain
plasticity, neuronal function and behavioural adaptation to neuropsychological
stress. Further corroborating this claim is the phenomenon that these epigenetic
changes correlate with the behavioural consequences of trauma exposure. Thereby,
epigenetic modifications provide a putative molecular mechanism by which the
behavioural phenotype and transcriptional/translational potential of genes
involved in HPA axis regulation can change drastically in response to
environmental challenges, and appear an important target for treatment of stress
related disorders. However, improved insight is required to increase their
therapeutic (drug) potential. Here, we provide an overview of the growing body of
literature describing the epigenetic modulation of the (primarily neuroendocrine)
stress response as a consequence of adult life stress and interpret the
implications for, and the challenges involved in applying this knowledge to, the
identification and treatment of stress-related psychiatric disorders.
PMID- 28400483
TI - Somatic and inherited mutations in primary aldosteronism.
AB - Primary aldosteronism (PA), the most common form of secondary hypertension, is
caused in the majority of cases by unilateral aldosterone-producing adenoma (APA)
or bilateral adrenal hyperplasia. Over the past few years, somatic mutations in
KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have been proven to be associated with APA
development, representing more than 50% of sporadic APA. The identification of
these mutations has allowed the development of a model for APA involving
modification on the intracellular ionic equilibrium and regulation of cell
membrane potential, leading to autonomous aldosterone overproduction.
Furthermore, somatic CTNNB1 mutations have also been identified in APA, but the
link between these mutations and APA development remains unknown. The sequence of
events responsible for APA formation is not completely understood, in particular,
whether a single hit or a double hit is responsible for both aldosterone
overproduction and cell proliferation. Germline mutations identified in patients
with early-onset PA have expanded the classification of familial forms (FH) of
PA. The description of germline KCNJ5 and CACNA1H mutations has identified FH-III
and FH-IV based on genetic findings; germline CACNA1D mutations have been
identified in patients with very early-onset PA and severe neurological
abnormalities. This review summarizes current knowledge on the genetic basis of
PA, the association of driver gene mutations and clinical findings and in the
contribution to patient care, plus the current understanding on the mechanisms of
APA development.
PMID- 28400485
TI - Imaging to Diagnose and Manage Patients in Heart Failure With Reduced Ejection
Fraction.
PMID- 28400486
TI - Anticoagulant-Associated Intracranial Hemorrhage in the Era of Reversal Agents.
PMID- 28400484
TI - Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin
binding protein A affect bond strength and fibronectin conformation.
AB - The Staphylococcus aureus cell surface contains cell wall-anchored proteins such
as fibronectin-binding protein A (FnBPA) that bind to host ligands (e.g.
fibronectin; Fn) present in the extracellular matrix of tissue or coatings on
cardiac implants. Recent clinical studies have found a correlation between
cardiovascular infections caused by S. aureus and nonsynonymous SNPs in FnBPA.
Atomic force microscopy (AFM), surface plasmon resonance (SPR), and molecular
simulations were used to investigate interactions between Fn and each of eight 20
mer peptide variants containing amino acids Ala, Asn, Gln, His, Ile, and Lys at
positions equivalent to 782 and/or 786 in Fn-binding repeat-9 of FnBPA.
Experimentally measured bond lifetimes (1/koff) and dissociation constants (Kd =
koff/kon), determined by mechanically dissociating the Fn.peptide complex at
loading rates relevant to the cardiovascular system, varied from the lowest
affinity H782A/K786A peptide (0.011 s, 747 MUm) to the highest-affinity
H782Q/K786N peptide (0.192 s, 15.7 MUm). These atomic force microscopy results
tracked remarkably well to metadynamics simulations in which peptide detachment
was defined solely by the free-energy landscape. Simulations and SPR experiments
suggested that an Fn conformational change may enhance the stability of the
binding complex for peptides with K786I or H782Q/K786I (Kdapp = 0.2-0.5 MUm, as
determined by SPR) compared with the lowest-affinity double-alanine peptide
(Kdapp = 3.8 MUm). Together, these findings demonstrate that amino acid
substitutions in Fn-binding repeat-9 can significantly affect bond strength and
influence the conformation of Fn upon binding. They provide a mechanistic
explanation for the observation of nonsynonymous SNPs in fnbA among clinical
isolates of S. aureus that cause endovascular infections.
PMID- 28400487
TI - Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to
Carotid Stenting Versus Endarterectomy.
AB - BACKGROUND AND PURPOSE: Complex vascular anatomy might increase the risk of
procedural stroke during carotid artery stenting (CAS). Randomized controlled
trial evidence that vascular anatomy should inform the choice between CAS and
carotid endarterectomy (CEA) has been lacking. METHODS: One-hundred eighty-four
patients with symptomatic internal carotid artery stenosis who were randomly
assigned to CAS or CEA in the ICSS (International Carotid Stenting Study)
underwent magnetic resonance (n=126) or computed tomographic angiography (n=58)
at baseline and brain magnetic resonance imaging before and after treatment. We
investigated the association between aortic arch configuration, angles of supra
aortic arteries, degree, length of stenosis, and plaque ulceration with the
presence of >=1 new ischemic brain lesion on diffusion-weighted magnetic
resonance imaging (DWI+) after treatment. RESULTS: Forty-nine of 97 patients in
the CAS group (51%) and 14 of 87 in the CEA group (16%) were DWI+ (odds ratio
[OR], 6.0; 95% confidence interval [CI], 2.9-12.4; P<0.001). In the CAS group,
aortic arch configuration type 2/3 (OR, 2.8; 95% CI, 1.1-7.1; P=0.027) and the
degree of the largest internal carotid artery angle (>=60 degrees versus <60
degrees ; OR, 4.1; 95% CI, 1.7-10.1; P=0.002) were both associated with DWI+,
also after correction for age. No predictors for DWI+ were identified in the CEA
group. The DWI+ risk in CAS increased further over CEA if the largest internal
carotid artery angle was >=60 degrees (OR, 11.8; 95% CI, 4.1-34.1) than if it
was <60 degrees (OR, 3.4; 95% CI, 1.2-9.8; interaction P=0.035). CONCLUSIONS:
Complex configuration of the aortic arch and internal carotid artery tortuosity
increase the risk of cerebral ischemia during CAS, but not during CEA. Vascular
anatomy should be taken into account when selecting patients for stenting.
CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN25337470. Unique
identifier: ISRCTN25337470.
PMID- 28400488
TI - Predictors of Dysphagia in Acute Pontine Infarction.
AB - BACKGROUND AND PURPOSE: Little is known about the frequency and the clinical
characteristics of neurogenic dysphagia in pontine strokes. In this study, we
sought to identify predictors for dysphagia in a cohort of patients with isolated
pontine infarctions. METHODS: We included all patients admitted to our department
between 2008 and 2014 having an acute (<48 hours after symptom onset) ischemic
stroke in the pons, as documented by means of diffusion-weighted magnetic
resonance imaging. Precise infarct localization was stratified according to
established vascular territories. The presence of dysphagia was the primary end
point of the study and was assessed by a Speech-Language Pathologist according to
defined criteria. RESULTS: The study recruited 59 patients, 14 with and 45
without dysphagia. Median (interquartile range) stroke severity (in terms of
National Institutes of Health Stroke Scale values) was higher in the dysphagic
group as compared with patients without dysphagia (8.5 [6-12] versus 2 [1-5];
P<0.001). Infarct localization in the upper part of the pons (78.6% versus 33.3%;
P=0.004) and in the anterolateral vascular territory (78.6% versus 31.1%;
P=0.002) occurred more often in the dysphagic group. In a multivariate model,
age, infarct volume, and National Institutes of Health Stroke Scale value were
independent predictors of dysphagia. CONCLUSIONS: Dysphagia occurs frequently in
patients with isolated pontine infarctions. Clinical and imaging predictors of
dysphagia may help to provide optimal screening, to prevent complications and to
improve long-term prognosis.
PMID- 28400489
TI - Diazoxide for Lowering Insulin Levels in Breast Cancer Patients.
PMID- 28400490
TI - Flavour chemicals in a sample of non-cigarette tobacco products without explicit
flavour names sold in New York City in 2015.
AB - BACKGROUND: Youth who experiment with tobacco often start with flavoured
products. In New York City (NYC), local law restricts sales of all tobacco
products with 'characterising flavours' except for 'tobacco, menthol, mint and
wintergreen'. Enforcement is based on packaging: explicit use of a flavour name
(eg, 'strawberry') or image depicting a flavour (eg, a fruit) is presumptive
evidence that a product is flavoured and therefore prohibited. However, a tobacco
product may contain significant levels of added flavour chemicals even when the
label does not explicitly use a flavour name. METHODS: Sixteen tobacco products
were purchased within NYC in 2015 that did not have explicit flavour names, along
with three with flavour names. These were analysed for 92 known flavour chemicals
plus triacetin by gas chromatography/mass spectrometry. RESULTS: 14 of the 16
products had total determined flavour chemical levels that were higher (>0.3
mg/g) than in previously studied flavour-labelled products and of a chemical
profile indicating added flavour chemicals. CONCLUSIONS: The results suggest that
the tobacco industry has responded to sales restrictions by renaming flavoured
products to avoid explicitly identifying them as flavoured. While chemical
analysis is the most precise means of identifying flavours in tobacco products,
federal tobacco laws pre-empt localities from basing regulations on that
approach, limiting enforcement options. If the Food and Drug Administration would
mandate that all tobacco products must indicate when flavourings are present
above a specific level, local jurisdictions could enforce their sales
restrictions. A level of 0.1 mg/g for total added flavour chemicals is suggested
here as a relevant reference value for regulating added flavour chemicals in
tobacco products.
PMID- 28400491
TI - ELF18-INDUCED LONG-NONCODING RNA Associates with Mediator to Enhance Expression
of Innate Immune Response Genes in Arabidopsis.
AB - The plant immune response is a complex process involving transcriptional and
posttranscriptional regulation of gene expression. Responses to plant immunity
are initiated upon the perception of pathogen-associated molecular patterns,
including peptide fragment of bacterial flagellin (flg22) or translation
elongation factor Tu (elf18). Here, we identify an Arabidopsis thaliana long
noncoding RNA, designated ELF18-INDUCED LONG-NONCODING RNA1 (ELENA1), as a factor
enhancing resistance against Pseudomonas syringe pv tomato DC3000. ELENA1
knockdown plants show decreased expression of PATHOGENESIS-RELATED GENE1 (PR1)
and the plants are susceptible to pathogens. By contrast, plants overexpressing
ELENA1 show elevated PR1 expression after elf18 treatment and display a pathogen
resistance phenotype. RNA-sequencing analysis of ELENA1-overexpressing plants
after elf18 treatment confirms increased expression of defense-related genes
compared with the wild type. ELENA1 directly interacts with Mediator subunit 19a
(MED19a) and affects enrichment of MED19a on the PR1 promoter. These results show
that MED19a regulates PR1 expression through ELENA1. Our findings uncover an
additional layer of complexity, implicating long-noncoding RNAs in the
transcriptional regulation of plant innate immunity.
PMID- 28400492
TI - The Molecular Dialog between Flowering Plant Reproductive Partners Defined by SNP
Informed RNA-Sequencing.
AB - The molecular interactions between reproductive cells are critical for
determining whether sexual reproduction between individuals results in
fertilization and can result in barriers to interspecific hybridization. However,
it is a challenge to define the complete molecular exchange between reproductive
partners because parents contribute to a complex mixture of cells during
reproduction. We unambiguously defined male- and female-specific patterns of gene
expression during Arabidopsis thaliana reproduction using single nucleotide
polymorphism-informed RNA-sequencing analysis. Importantly, we defined the
repertoire of pollen tube-secreted proteins controlled by a group of MYB
transcription factors that are required for sperm release from the pollen tube to
the female gametes, a critical barrier to interspecific hybridization. Our work
defines the pollen tube gene products that respond to the pistil and are required
for reproductive success; moreover, we find that these genes are highly
evolutionarily plastic both at the level of coding sequence and expression across
A. thaliana accessions.
PMID- 28400493
TI - A Virus-Induced Assay for Functional Dissection and Analysis of Monocot and Dicot
Flowering Time Genes.
AB - Virus-induced flowering (VIF) uses virus vectors to express Flowering Locus T
(FT) to induce flowering in plants. This approach has recently attracted wide
interest for its practical applications in accelerating breeding in crops and
woody fruit trees. However, the insight into VIF and its potential as a powerful
tool for dissecting florigenic proteins remained to be elucidated. Here, we
describe the mechanism and further applications of Potato virus X (PVX)-based VIF
in the short-day Nicotiana tabacum cultivar Maryland Mammoth. Ectopic delivery of
Arabidopsis (Arabidopsis thaliana) AtFT by PVX/AtFT did not induce the expression
of the endogenous FT ortholog NtFT4; however, it was sufficient to trigger
flowering in Maryland Mammoth plants grown under noninductive long-day
conditions. Infected tobacco plants developed no systemic symptoms, and the PVX
based VIF did not cause transgenerational flowering. We showed that the PVX-based
VIF is a much more rapid method to examine the impacts of single amino acid
mutations on AtFT for floral induction than making individual transgenic
Arabidopsis lines for each mutation. We also used the PVX-based VIF to
demonstrate that adding a His- or FLAG-tag to the N or C terminus of AtFT could
affect its florigenic activity and that this system can be applied to assay the
function of FT genes from heterologous species, including tomato (Solanum
lycopersicum) SFT and rice (Oryza sativa) Hd3a Thus, the PVX-based VIF represents
a simple and efficient system to identify individual amino acids that are
essential for FT-mediated floral induction and to test the ability of mono- and
dicotyledonous FT genes and FT fusion proteins to induce flowering.
PMID- 28400494
TI - UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and
Gibberellin Levels.
AB - Ultraviolet-B (UV-B) radiation affects leaf growth in a wide range of species. In
this work, we demonstrate that UV-B levels present in solar radiation inhibit
maize (Zea mays) leaf growth without causing any other visible stress symptoms,
including the accumulation of DNA damage. We conducted kinematic analyses of cell
division and expansion to understand the impact of UV-B radiation on these
cellular processes. Our results demonstrate that the decrease in leaf growth in
UV-B-irradiated leaves is a consequence of a reduction in cell production and a
shortened growth zone (GZ). To determine the molecular pathways involved in UV-B
inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of
control and UV-B-exposed plants. Our results show a link between the observed
leaf growth inhibition and the expression of specific cell cycle and
developmental genes, including growth-regulating factors (GRFs) and transcripts
for proteins participating in different hormone pathways. Interestingly, the
decrease in the GZ size correlates with a decrease in the concentration of GA19,
the immediate precursor of the active gibberellin, GA1, by UV-B in this zone,
which is regulated, at least in part, by the expression of GRF1 and possibly
other transcription factors of the GRF family.
PMID- 28400495
TI - Constitutively Active Arabidopsis MAP Kinase 3 Triggers Defense Responses
Involving Salicylic Acid and SUMM2 Resistance Protein.
AB - Mitogen-activated protein kinases (MAPKs) are important regulators of plant
immunity. Most of the knowledge about the function of these pathways is derived
from loss-of-function approaches. Using a gain-of-function approach, we
investigated the responses controlled by a constitutively active (CA) MPK3 in
Arabidopsis thalianaCA-MPK3 plants are dwarfed and display a massive derepression
of defense genes associated with spontaneous cell death as well as the
accumulation of reactive oxygen species, phytoalexins, and the stress-related
hormones ethylene and salicylic acid (SA). Remarkably CA-MPK3/sid2 and CA
MPK3/ein2-50 lines, which are impaired in SA synthesis and ethylene signaling,
respectively, retain most of the CA-MPK3-associated phenotypes, indicating that
the constitutive activity of MPK3 can bypass SA and ethylene signaling to
activate defense responses. A comparative analysis of the molecular phenotypes of
CA-MPK3 and mpk4 autoimmunity suggested convergence between the MPK3- and MPK4
guarding modules. In support of this model, CA-MPK3 crosses with summ1 and summ2,
two known suppressors of mpk4, resulted in a partial reversion of the CA-MPK3
phenotypes. Overall, our data unravel a novel mechanism by which the MAPK
signaling network contributes to a robust defense-response system.
PMID- 28400496
TI - Pea Border Cell Maturation and Release Involve Complex Cell Wall Structural
Dynamics.
AB - The adhesion of plant cells is vital for support and protection of the plant body
and is maintained by a variety of molecular associations between cell wall
components. In some specialized cases, though, plant cells are programmed to
detach, and root cap-derived border cells are examples of this. Border cells (in
some species known as border-like cells) provide an expendable barrier between
roots and the environment. Their maturation and release is an important but
poorly characterized cell separation event. To gain a deeper insight into the
complex cellular dynamics underlying this process, we undertook a systematic,
detailed analysis of pea (Pisum sativum) root tip cell walls. Our study included
immunocarbohydrate microarray profiling, monosaccharide composition
determination, Fourier-transformed infrared microspectroscopy, quantitative
reverse transcription-PCR of cell wall biosynthetic genes, analysis of hydrolytic
activities, transmission electron microscopy, and immunolocalization of cell wall
components. Using this integrated glycobiology approach, we identified multiple
novel modes of cell wall structural and compositional rearrangement during root
cap growth and the release of border cells. Our findings provide a new level of
detail about border cell maturation and enable us to develop a model of the
separation process. We propose that loss of adhesion by the dissolution of
homogalacturonan in the middle lamellae is augmented by an active biophysical
process of cell curvature driven by the polarized distribution of xyloglucan and
extensin epitopes.
PMID- 28400497
TI - C57BL/6J mice as a polygenic developmental model of diet-induced obesity.
AB - Susceptibility to obesity changes during the course of life. We utilized the
C57BL/6J (B6) and 129S mouse as a genetic model for variation in diet-induced
obesity to define the adiposity phenotypes from birth to maturity at 8 weeks-of
age. From birth to 8 weeks-of-age, both male and female 129S mice had
significantly higher fat mass and adiposity index than B6 mice, although they
were not obese. After 8 weeks-of-age, B6 had greater adiposity/obesity than 129S
mice in response to a high fat (HF). We sought to determine the mechanism
activating the fat accumulation in B6 mice at 8-weeks-of-age. We used microarray
analysis of gene expression during development of inguinal fat to show that
molecular networks of lipogenesis were maximally expressed at 8 weeks-of-age. In
addition, the DNA methylation analysis of the Sfrp5 promoter and binding of
acetylated histones to Sfrp5 and Acly promoter regions showed that major
differences in the expression of genes of lipogenesis and chromatin structure
occur during development. Differences in lipogenesis networks could account for
the strain-dependent differences in adiposity up to 8 weeks-of-age; however,
changes in the expression of genes in these networks were not associated with the
susceptibility to DIO in B6 male mice beyond 8 weeks-of-age.
PMID- 28400498
TI - Effect of thoracic epidural anesthesia on heart rate variability in a porcine
model.
AB - Heart rate variability (HRV) is increasingly recognized as a means of evaluating
autonomic tone. Thoracic epidural anesthesia (TEA) has been previously
demonstrated to suppress the electrical storms in patients. However, the effect
of TEA on HRV during sympathoexcitation remains unknown. In this study, we aimed
to determine the effects of TEA on HRV response to left stellate ganglion
stimulation (LSS) in a porcine model. In 12 anesthetized pigs after insertion of
an epidural catheter to T1 level, a median sternotomy was performed to expose the
heart and the left stellate ganglion. A 56-electrode sock was used for obtaining
epicardial activation recovery interval (ARI). Animal received LSS at 4 Hz for 30
sec. After 30 min of bupivacaine epidural injection, LSS was performed in the
same way as the baseline condition. LSS significantly increased low-frequency
normalized units (LF: 44.9 +/- 6.7 vs. 13.6 +/- 3.1 msec2 baseline, P < 0.05) and
decreased high-frequency normalized units (HF: 11.5 +/- 4.6 vs. 41.9 +/- 5.1
msec2 baseline, P < 0.05). As a result, LF/HF significantly increased from 0.3 +/
0.2 to 3.9 +/- 1.4 during LSS TEA significantly attenuated the LF/HF from 3.9 +/
1.4 to 1.6 +/- 0.8 with increased HF components from 11.5 +/- 4.6 to 26.5 +/-
3.2 msec2 LF component significantly correlates with global ARI (r = -0.81) and
dispersion of repolarization (r = 0.85). HRV can precisely reflect the cardiac
autonomic tone and TEA modulates the HRV by enhancing the HF components probably
through a parasympathetic nerve system.
PMID- 28400499
TI - The coherence of macrocirculation, microcirculation, and tissue metabolic
response during nontraumatic hemorrhagic shock in swine.
AB - Hemorrhagic shock is clinically observed as changes in macrocirculatory indices,
while its main pathological constituent is cellular asphyxia due to
microcirculatory alterations. The coherence between macro- and microcirculatory
changes in different shock states has been questioned. This also applies to the
hemorrhagic shock. Most studies, as well as clinical situations, of hemorrhagic
shock include a "second hit" by tissue trauma. It is therefore unclear to what
extent the hemorrhage itself contributes to this lack of circulatory coherence.
Nine pigs in general anesthesia were exposed to a controlled withdrawal of 50% of
their blood volume over 30 min, and then retransfusion over 20 min after 70 min
of hypovolemia. We collected macrocirculatory variables, microcirculatory blood
flow measurement by the fluorescent microspheres technique, as well as global
microcirculatory patency by calculation of Pv-aCO2, and tissue metabolism
measurement by the use of microdialysis. The hemorrhage led to anticipated
changes in macrocirculatory variables with a coherent change in microcirculatory
and metabolic variables. In the late hemorrhagic phase, the animals' variables
generally improved, probably through recruitment of venous blood reservoirs.
After retransfusion, all variables were normalized and remained same throughout
the study period. We find in our nontraumatic model consistent coherence between
changes in macrocirculatory indices, microcirculatory blood flow, and tissue
metabolic response during hemorrhagic shock and retransfusion. This indicates
that severe, but brief, hemorrhage with minimal tissue injury is in itself not
sufficient to cause lack of coherence between macro- and microcirculation.
PMID- 28400500
TI - Differential hemodynamic and respiratory responses to right and left cervical
vagal nerve stimulation in rats.
AB - Neuromodulation through vagal nerve stimulation (VNS) is currently explored for a
variety of clinical conditions. However, there are no established VNS parameters
for animal models of human diseases, such as hypertension. Therefore, the aim of
this study was to assess hemodynamic and respiratory responses to right- or left
sided cervical VNS in a hypertensive rat model. Anesthetized stroke-prone
spontaneously hypertensive rats were instrumented for arterial blood pressure and
heart rate monitoring and left- or right-sided VNS Cervical VNS was applied
through bipolar coil electrodes. Stimulation parameters tested were 3 V and 6 V,
2 Hz to 20 Hz stimulation frequency, and 50 MUsec to 20 msec pulse duration. Each
combination of stimulation parameters was applied twice with altered polarity,
that is, anode and cathode in the cranial and caudal position. Respiration rate
was derived from systolic blood pressure fluctuations. In general, cervical VNS
caused bradycardia, hypotension, and tachypnea. These responses were more
pronounced with left-sided than with right-sided VNS and depended on the
stimulation voltage, stimulation frequency, and pulse duration, but not on the
polarity of stimulation. Furthermore, the results suggest that at low stimulation
frequencies (<5 Hz) and short pulse durations (<0.5 msec) primarily larger A
fibers are activated, while at longer pulse durations (>0.5 msec) smaller B
fibers are also recruited. In conclusion, in rats left-sided cervical VNS causes
greater cardio-respiratory responses than right-sided VNS and at lower
stimulation frequencies (e.g., 5 Hz), longer pulse durations (>0.5 msec) seem to
be required to consistently recruit B-fibers in addition to A-fibers.
PMID- 28400501
TI - Contribution of minced muscle graft progenitor cells to muscle fiber formation
after volumetric muscle loss injury in wild-type and immune deficient mice.
AB - Volumetric muscle injury (VML) causes an irrecoverable loss of muscle fibers,
persistent strength deficits, and chronic disability. A crucial challenge to VML
injury and possible regeneration is the removal of all of the in situ native
elements necessary for skeletal muscle regeneration. Our first goal was to
establish a reliable VML model in the mouse tibialis anterior (TA) muscle. In
adult male wild-type and nude mice, a non-repaired ~20% VML injury to the TA
muscle resulted in an ~59% loss in nerve evoked muscle strength, ~33% loss in
muscle mass, and ~29% loss of muscle fibers at 28 day post-injury. Our second
goal was to investigate if minced muscle grafts (~1 mm3 tissue fragments) promote
recovery of muscle fibers after VML injury and to understand if the graft-derived
progenitor cells directly contribute to fiber regeneration. To assess donor cell
contribution, donor muscle tissue was derived from UBC-GFP mice in a subset of
experiments. Minced grafts restored ~34% of the lost fibers 28 days post-injury.
The number of GFP+ fibers and the estimated number of regenerated fibers were
similar, regardless of host mouse strain. The muscle tissue regeneration promoted
by minced grafts did not improve TA muscle strength at this time post-injury.
These findings demonstrate the direct contribution of minced muscle graft-derived
myogenic stem/progenitor cells to recovery of muscle fibers after VML injury and
signify the utility of autologous myogenic stem cell therapies for this
indication.
PMID- 28400502
TI - Cholinergic agonists reduce blood pressure in a mouse model of systemic lupus
erythematosus.
AB - Increased inflammation arising from an abnormal immune response can damage
healthy tissue and lead to disease progression. An important example of this is
the accumulation of inflammatory mediators in the kidney, which can subsequently
lead to hypertension and renal injury. The origin of this inflammation may
involve neuro-immune interactions. For example, the novel vagus nerve-to-spleen
mechanism known as the "cholinergic anti-inflammatory pathway" controls
inflammation upon stimulation. However, if this pathway is dysfunctional,
inflammation becomes less regulated and chronic inflammatory diseases such as
hypertension may develop. Systemic lupus erythematosus (SLE) is an autoimmune
disease with aberrant immune function, increased renal inflammation, and
prevalent hypertension. We hypothesized that the cholinergic anti-inflammatory
pathway is impaired in SLE and that stimulation of this pathway would protect
from the progression of hypertension in SLE mice. Female SLE (NZBWF1) and control
(NZW) mice were administered nicotine or vehicle for 7 days (2 mg/kg/day,
subcutaneously) in order to stimulate the cholinergic anti-inflammatory pathway
at the level of the splenic nicotinic acetylcholine receptor (alpha7-nAChR).
Blood pressure was assessed posttreatment. Nicotine-treated SLE mice did not
develop hypertension and this lower blood pressure (compared to saline-treated
SLE mice) coincided with lower splenic and renal cortical expression of pro
inflammatory cytokines. These data provide evidence that the cholinergic anti
inflammatory pathway is impaired in SLE In addition, these data suggest that
stimulation of the cholinergic anti-inflammatory pathway can protect the kidney
by dampening inflammation and therefore prevent the progression of hypertension
in the setting of SLE.
PMID- 28400503
TI - PGC-1alpha and fasting-induced PDH regulation in mouse skeletal muscle.
AB - The purpose of the present study was to examine whether lack of skeletal muscle
peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha)
affects the switch in substrate utilization from a fed to fasted state and the
fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle.
Skeletal muscle-specific PGC-1alpha knockout (MKO) mice and floxed littermate
controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased
phosphorylation of all four known sites on PDH-E1alpha and increased pyruvate
dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not
alter total acetylation of PDH-E1alpha Lack of muscle PGC-1alpha did not affect
the switch from glucose to fat oxidation in the transition from the fed to fasted
state, but was associated with lower and higher respiratory exchange ratio (RER)
in the fed and fasted state, respectively. PGC-1alpha MKO mice had lower skeletal
muscle PDH-E1alpha, PDK1, 2, 4, and pyruvate dehydrogenase phosphatase (PDP1)
protein content than controls, but this did not prevent the fasting-induced
increase in PDH-E1alpha phosphorylation in PGC-1alpha MKO mice. However, lack of
skeletal muscle PGC-1alpha reduced SIRT3 protein content, increased total lysine
PDH-E1alpha acetylation in the fed state, and prevented a fasting-induced
increase in SIRT3 protein. In conclusion, skeletal muscle PGC-1alpha is required
for fasting-induced upregulation of skeletal muscle SIRT3 and maintaining high
fat oxidation in the fasted state, but is dispensable for preserving the
capability to switch substrate during the transition from the fed to the fasted
state and for fasting-induced PDH regulation in skeletal muscle.
PMID- 28400504
TI - Cardiopulmonary phenotype associated with human PHD2 mutation.
AB - Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia
inducible factor (HIF) family of transcription factors. When oxygen is plentiful,
HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase
domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL)
ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is
scarce, the PHD enzymes are inactivated, leading to HIF accumulation and
upregulation not only of erythropoietin expression, but also the expression of
hundreds of other genes, including those coordinating cardiovascular and
ventilatory adaptation to hypoxia. Nevertheless, despite the identification of
over 50 mutations in the PHD-HIF-VHL pathway in patients with previously
unexplained congenital erythrocytosis, there are very few reports of associated
cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and
ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis
secondary to heterozygous mutation in PHD2, the most abundant of the PHD
isoforms. We compare this phenotype with that reported in patients with the
archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss
the possible clinical implications of our findings, particularly in the light of
the emerging role for small molecule PHD inhibitors in clinical practice.
PMID- 28400505
TI - No effect of ascorbate on cutaneous vasodilation and sweating in older men and
those with type 2 diabetes exercising in the heat.
AB - Aging and chronic disease such as type 2 diabetes (T2D) are associated with
impairments in the body's ability to dissipate heat. To reduce the risk of heat
related injuries in these heat vulnerable individuals, it is necessary to
identify interventions that can attenuate this impairment. We evaluated the
hypothesis that intradermal administration of ascorbate improves cutaneous
vasodilation and sweating in older adults via nitric oxide synthase (NOS)
dependent mechanisms during exercise in the heat and whether these improvements,
if any, are greater in individuals with T2D. Older males with (n = 12, 61 +/- 9
years) and without (n = 12, 64 +/- 7 years) T2D performed two 30-min bouts of
cycling at a fixed rate of metabolic heat production of 500 W (~70% peak oxygen
uptake) in the heat (35 degrees C); each followed by a 20- and 40-min recovery,
respectively. Cutaneous vascular conductance (CVC) and sweat rate were measured
at four intradermal microdialysis sites treated with either (1) lactated Ringer
(Control), (2) 10 mmol/L ascorbate (an antioxidant), (3) 10 mmol/L L-NAME (non
selective NOS inhibitor), or (4) a combination of ascorbate + L-NAME. In both
groups, ascorbate did not modulate CVC or sweating during exercise relative to
Control (all P > 0.05). In comparison to Control, L-NAME alone or combined with
ascorbate attenuated CVC during exercise (all P <= 0.05) but had no influence on
sweating (all P > 0.05). We show that in both healthy and T2D older adults,
intradermal administration of ascorbate does not improve cutaneous vasodilation
and sweating during exercise in the heat. However, NOS plays an important role in
mediating cutaneous vasodilation.
PMID- 28400506
TI - Acute elevations in serum hormones are attenuated after chronic training with
traditional isoinertial but not accentuated eccentric loads in strength-trained
men.
AB - It has been proposed that the maintenance of acute hormonal responses reveal an
efficacy of a training stimulus to evoke ongoing increases in strength and muscle
mass. We previously observed that maximum strength continued to improve
throughout a 10-week period in an accentuated eccentric loading group (AEL) but
not a traditional isoinertial loading (ISO) group. Therefore, this study
investigated whether the magnitude of acute hormonal responses was greater (i.e.,
maintained) in AEL compared to ISO at the end of the training period. Subjects in
AEL (eccentric load = concentric load + 40%) and ISO performed experimental
loading tests (three sets of 10 repetitions in the leg press and knee extension
exercises) during weeks 2 and 9 of the training period. Blood samples collected
during these experimental loadings were analyzed for serum testosterone, growth
hormone and cortisol concentrations. Maximum isometric knee extension torque
(MVC) and lower-limb lean mass were assessed before and after 5 and 10 weeks of
training. Acute testosterone, growth hormone and cortisol responses to
traditional isoinertial loading were reduced at the end of the training period
but were not reduced after accentuated eccentric load training (P < 0.05-0.1
between-groups). Increases in MVC and lower-limb lean mass over weeks 6-10 were
greater in AEL compared to ISO (MVC: 7.3 +/- 5.4 vs. -0.4 +/- 7.2%, P = 0.026 for
between-group difference; lower-limb lean mass: 1.6 +/- 2.2 vs. -0.2 +/- 1.4%, P
= 0.063 for between-group difference). The maintenance of acute hormonal
responses and continued strength gain in AEL but not ISO are consistent with the
hypothesis that maintained acute responses indicate an efficacy of a training
stimulus to evoke ongoing adaptation. However, since relationships between
hormonal responses and training-induced adaptations were not statistically
significant, the data suggest that tracking of acute hormonal responses on an
individual level may not provide a sensitive enough guide for decisions regarding
program design and periodization.
PMID- 28400507
TI - Effects of unilateral airway occlusion on rib motion and inspiratory intercostal
activity in dogs.
AB - Unilateral bronchial occlusion, a complication of many lung diseases, causes
dyspnea but the mechanism of this symptom is uncertain. In this study,
electromyographic (EMG) activity in the parasternal and external intercostal
muscles in the third intercostal space and inspiratory motion of the third rib on
both sides of the thorax were assessed during occlusion of a main bronchus for a
single breath in anesthetized dogs. Occlusion produced a 65% increase in external
intercostal EMG activity in both hemithoraces without altering parasternal EMG
activity. Concomitantly, the inspiratory cranial rib motion showed a 50% decrease
on both sides of the thorax. These changes were unaffected by bilateral vagotomy.
However, when an external, caudally oriented force was applied to the third rib
on the right or left side so that its inspiratory cranial displacement was
abolished, activity in the adjacent external intercostals showed a twofold
increase, but rib motion and external activity in the contralateral hemithorax
remained unchanged. It is concluded that during occlusion of a main bronchus, the
increase in external intercostal activity is induced by the decrease in
inspiratory cranial rib displacement in both hemithoraces, and that this decrease
is determined by the increase in pleural pressure swings on both sides of the
mediastinum. This mechanism, combined with the decrease in PaO2, induces similar
alterations when unilateral bronchial occlusion is maintained for a series of
consecutive breaths.
PMID- 28400508
TI - ACOX2 deficiency in primary malignant cardiac tumors.
PMID- 28400509
TI - Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid
signatures associated with lung adenocarcinoma.
AB - KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been
associated with altered glucose and glutamine metabolism. Here, we show that KRAS
activates lipogenesis, and this activation results in distinct proteomic and
lipid signatures. By gene expression analysis, KRAS is shown to be associated
with a lipogenesis gene signature and specific induction of fatty acid synthase
(FASN). Through desorption electrospray ionization MS imaging (DESI-MSI),
specific changes in lipogenesis and specific lipids are identified. By the
nanoimmunoassay (NIA), KRAS is found to activate the protein ERK2, whereas ERK1
activation is found in non-KRAS-associated human lung tumors. The inhibition of
FASN by cerulenin, a small molecule antibiotic, blocked cellular proliferation of
KRAS-associated lung cancer cells. Hence, KRAS is associated with activation of
ERK2, induction of FASN, and promotion of lipogenesis. FASN may be a unique
target for KRAS-associated lung adenocarcinoma remediation.
PMID- 28400510
TI - Malate-dependent Fe accumulation is a critical checkpoint in the root
developmental response to low phosphate.
AB - Low phosphate (Pi) availability constrains plant development and seed production
in both natural and agricultural ecosystems. When Pi is scarce, modifications of
root system architecture (RSA) enhance the soil exploration ability of the plant
and lead to an increase in Pi uptake. In Arabidopsis, an iron-dependent mechanism
reprograms primary root growth in response to low Pi availability. This program
is activated upon contact of the root tip with low-Pi media and induces premature
cell differentiation and the arrest of mitotic activity in the root apical
meristem, resulting in a short-root phenotype. However, the mechanisms that
regulate the primary root response to Pi-limiting conditions remain largely
unknown. Here we report on the isolation and characterization of two low-Pi
insensitive mutants (lpi5 and lpi6), which have a long-root phenotype when grown
in low-Pi media. Cellular, genomic, and transcriptomic analysis of low-Pi
insensitive mutants revealed that the genes previously shown to underlie
Arabidopsis Al tolerance via root malate exudation, known as SENSITIVE TO PROTON
RHIZOTOXICITY (STOP1) and ALUMINUM ACTIVATED MALATE TRANSPORTER 1 (ALMT1),
represent a critical checkpoint in the root developmental response to Pi
starvation in Arabidopsis thaliana Our results also show that exogenous malate
can rescue the long-root phenotype of lpi5 and lpi6 Malate exudation is required
for the accumulation of Fe in the apoplast of meristematic cells, triggering the
differentiation of meristematic cells in response to Pi deprivation.
PMID- 28400511
TI - SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR
dependent manner.
AB - Many DNA repair proteins have additional functions other than their roles in DNA
repair. In addition to catalyzing PCNA polyubiquitylation in response to the
stalling of DNA replication, SHPRH has the additional function of facilitating
rRNA transcription by localizing to the ribosomal DNA (rDNA) promoter in the
nucleoli. SHPRH was recruited to the rDNA promoter using its plant homeodomain
(PHD), which interacts with histone H3 when the fourth lysine of H3 is not
trimethylated. SHPRH enrichment at the rDNA promoter was inhibited by cell
starvation, by treatment with actinomycin D or rapamycin, or by depletion of
CHD4. SHPRH also physically interacted with the RNA polymerase I complex. Taken
together, we provide evidence that SHPRH functions in rRNA transcription through
its interaction with histone H3 in a mammalian target of rapamycin (mTOR)
dependent manner.
PMID- 28400512
TI - Convergence of DNA methylation and phosphorothioation epigenetics in bacterial
genomes.
AB - Explosive growth in the study of microbial epigenetics has revealed a diversity
of chemical structures and biological functions of DNA modifications in
restriction-modification (R-M) and basic genetic processes. Here, we describe the
discovery of shared consensus sequences for two seemingly unrelated DNA
modification systems, 6mA methylation and phosphorothioation (PT), in which
sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric
analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro
87, strains possessing PT-based R-M genes, revealed d(GPS6mA) dinucleotides in
the GPS6mAAC consensus representing ~5% of the 1,100 to 1,300 PT-modified d(GPSA)
motifs per genome, with 6mA arising from a yet-to-be-identified
methyltransferase. To further explore PT and 6mA in another consensus sequence,
GPS6mATC, we engineered a strain of E. coli HST04 to express Dnd genes from
Hahella chejuensis KCTC2396 (PT in GPSATC) and Dam methyltransferase from E. coli
DH10B (6mA in G6mATC). Based on this model, in vitro studies revealed reduced Dam
activity in GPSATC-containing oligonucleotides whereas single-molecule real-time
sequencing of HST04 DNA revealed 6mA in all 2,058 GPSATC sites (5% of 37,698
total GATC sites). This model system also revealed temperature-sensitive
restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that
6mA can substitute for PT to confer resistance to restriction by the DndFGH
system. These results point to complex but unappreciated interactions between DNA
modification systems and raise the possibility of coevolution of interacting
systems to facilitate the function of each.
PMID- 28400513
TI - Determining the factors driving selective effects of new nonsynonymous mutations.
AB - The distribution of fitness effects (DFE) of new mutations plays a fundamental
role in evolutionary genetics. However, the extent to which the DFE differs
across species has yet to be systematically investigated. Furthermore, the
biological mechanisms determining the DFE in natural populations remain unclear.
Here, we show that theoretical models emphasizing different biological factors at
determining the DFE, such as protein stability, back-mutations, species
complexity, and mutational robustness make distinct predictions about how the DFE
will differ between species. Analyzing amino acid-changing variants from natural
populations in a comparative population genomic framework, we find that humans
have a higher proportion of strongly deleterious mutations than Drosophila
melanogaster. Furthermore, when comparing the DFE across yeast, Drosophila, mice,
and humans, the average selection coefficient becomes more deleterious with
increasing species complexity. Last, pleiotropic genes have a DFE that is less
variable than that of nonpleiotropic genes. Comparing four categories of
theoretical models, only Fisher's geometrical model (FGM) is consistent with our
findings. FGM assumes that multiple phenotypes are under stabilizing selection,
with the number of phenotypes defining the complexity of the organism. Our
results suggest that long-term population size and cost of complexity drive the
evolution of the DFE, with many implications for evolutionary and medical
genomics.
PMID- 28400514
TI - Role of surface and subsurface processes in scaling N2O emissions along riverine
networks.
AB - Riverine environments, such as streams and rivers, have been reported as sources
of the potent greenhouse gas nitrous oxide ([Formula: see text]) to the
atmosphere mainly via microbially mediated denitrification. Our limited
understanding of the relative roles of the near-surface streambed sediment
(hyporheic zone), benthic, and water column zones in controlling [Formula: see
text] production precludes predictions of [Formula: see text] emissions along
riverine networks. Here, we analyze [Formula: see text] emissions from streams
and rivers worldwide of different sizes, morphology, land cover, biomes, and
climatic conditions. We show that the primary source of [Formula: see text]
emissions varies with stream and river size and shifts from the hyporheic-benthic
zone in headwater streams to the benthic-water column zone in rivers. This
analysis reveals that [Formula: see text] production is bounded between two
[Formula: see text] emission potentials: the upper [Formula: see text] emission
potential results from production within the benthic-hyporheic zone, and the
lower [Formula: see text] emission potential reflects the production within the
benthic-water column zone. By understanding the scaling nature of [Formula: see
text] production along riverine networks, our framework facilitates predictions
of riverine [Formula: see text] emissions globally using widely accessible
chemical and hydromorphological datasets and thus, quantifies the effect of human
activity and natural processes on [Formula: see text] production.
PMID- 28400516
TI - Community trust reduces myopic decisions of low-income individuals.
AB - Why do the poor make shortsighted choices in decisions that involve delayed
payoffs? Foregoing immediate rewards for larger, later rewards requires that
decision makers (i) believe future payoffs will occur and (ii) are not forced to
take the immediate reward out of financial need. Low-income individuals may be
both less likely to believe future payoffs will occur and less able to forego
immediate rewards due to higher financial need; they may thus appear to discount
the future more heavily. We propose that trust in one's community-which, unlike
generalized trust, we find does not covary with levels of income-can partially
offset the effects of low income on myopic decisions. Specifically, we
hypothesize that low-income individuals with higher community trust make less
myopic intertemporal decisions because they believe their community will buffer,
or cushion, against their financial need. In archival data and laboratory
studies, we find that higher levels of community trust among low-income
individuals lead to less myopic decisions. We also test our predictions with a 2
y community trust intervention in rural Bangladesh involving 121 union councils
(the smallest rural administrative and local government unit) and find that
residents in treated union councils show higher levels of community trust and
make less myopic intertemporal choices than residents in control union councils.
We discuss the implications of these results for the design of domestic and
global policy interventions to help the poor make decisions that could alleviate
poverty.
PMID- 28400515
TI - SAGA complex mediates the transcriptional up-regulation of antiviral RNA
silencing.
AB - Pathogen recognition and transcriptional activation of defense-related genes are
crucial steps in cellular defense responses. RNA silencing (RNAi) functions as an
antiviral defense in eukaryotic organisms. Several RNAi-related genes are known
to be transcriptionally up-regulated upon virus infection in some host organisms,
but little is known about their induction mechanism. A phytopathogenic
ascomycete, Cryphonectria parasitica (chestnut blight fungus), provides a
particularly advantageous system to study RNAi activation, because its infection
by certain RNA viruses induces the transcription of dicer-like 2 (dcl2) and
argonaute-like 2 (agl2), two major RNAi players. To identify cellular factors
governing activation of antiviral RNAi in C. parasitica, we developed a screening
protocol entailing multiple transformations of the fungus with cDNA of a
hypovirus mutant lacking the RNAi suppressor (CHV1-Deltap69), a reporter
construct with a GFP gene driven by the dcl2 promoter, and a random mutagenic
construct. Screening for GFP-negative colonies allowed the identification of
sgf73, a component of the SAGA (Spt-Ada-Gcn5 acetyltransferase) complex, a well
known transcriptional coactivator. Knockout of other SAGA components showed that
the histone acetyltransferase module regulates transcriptional induction of dcl2
and agl2, whereas histone deubiquitinase mediates regulation of agl2 but not dcl2
Interestingly, full-scale induction of agl2 and dcl2 by CHV1-Deltap69 required
both DCL2 and AGL2, whereas that by another RNA virus, mycoreovirus 1, required
only DCL2, uncovering additional roles for DCL2 and AGL2 in viral recognition
and/or RNAi activation. Overall, these results provide insight into the mechanism
of RNAi activation.
PMID- 28400517
TI - Aggregation landscapes of Huntingtin exon 1 protein fragments and the critical
repeat length for the onset of Huntington's disease.
AB - Huntington's disease (HD) is a neurodegenerative disease caused by an abnormal
expansion in the polyglutamine (polyQ) track of the Huntingtin (HTT) protein. The
severity of the disease depends on the polyQ repeat length, arising only in
patients with proteins having 36 repeats or more. Previous studies have shown
that the aggregation of N-terminal fragments (encoded by HTT exon 1) underlies
the disease pathology in mouse models and that the HTT exon 1 gene product can
self-assemble into amyloid structures. Here, we provide detailed structural
mechanisms for aggregation of several protein fragments encoded by HTT exon 1 by
using the associative memory, water-mediated, structure and energy model (AWSEM)
to construct their free energy landscapes. We find that the addition of the N
terminal 17-residue sequence ([Formula: see text]) facilitates polyQ aggregation
by encouraging the formation of prefibrillar oligomers, whereas adding the C
terminal polyproline sequence ([Formula: see text]) inhibits aggregation. The
combination of both terminal additions in HTT exon 1 fragment leads to a complex
aggregation mechanism with a basic core that resembles that found for the
aggregation of pure polyQ repeats using AWSEM. At the extrapolated physiological
concentration, although the grand canonical free energy profiles are uphill for
HTT exon 1 fragments having 20 or 30 glutamines, the aggregation landscape for
fragments with 40 repeats has become downhill. This computational prediction
agrees with the critical length found for the onset of HD and suggests potential
therapies based on blocking early binding events involving the terminal additions
to the polyQ repeats.
PMID- 28400518
TI - Pseudomagnetic fields for sound at the nanoscale.
AB - There is a growing effort in creating chiral transport of sound waves. However,
most approaches so far have been confined to the macroscopic scale. Here, we
propose an approach suitable to the nanoscale that is based on pseudomagnetic
fields. These pseudomagnetic fields for sound waves are the analogue of what
electrons experience in strained graphene. In our proposal, they are created by
simple geometrical modifications of an existing and experimentally proven
phononic crystal design, the snowflake crystal. This platform is robust,
scalable, and well-suited for a variety of excitation and readout mechanisms,
among them optomechanical approaches.
PMID- 28400519
TI - Balance of microtubule stiffness and cortical tension determines the size of
blood cells with marginal band across species.
AB - The fast bloodstream of animals is associated with large shear stresses. To
withstand these conditions, blood cells have evolved a special morphology and a
specific internal architecture to maintain their integrity over several weeks.
For instance, nonmammalian red blood cells, mammalian erythroblasts, and
platelets have a peripheral ring of microtubules, called the marginal band, that
flattens the overall cell morphology by pushing on the cell cortex. In this work,
we model how the shape of these cells stems from the balance between marginal
band rigidity and cortical tension. We predict that the diameter of the cell
scales with the total microtubule polymer and verify the predicted law across a
wide range of species. Our analysis also shows that the combination of the
marginal band rigidity and cortical tension increases the ability of the cell to
withstand forces without deformation. Finally, we model the marginal band coiling
that occurs during the disk-to-sphere transition observed, for instance, at the
onset of blood platelet activation. We show that when cortical tension increases
faster than cross-linkers can unbind, the marginal band will coil, whereas if the
tension increases more slowly, the marginal band may shorten as microtubules
slide relative to each other.
PMID- 28400520
TI - Reply to Marchio et al.: Antitumor immune regulation by angiostatic therapy.
PMID- 28400521
TI - An antivascular vaccine to boost self-immunity and strike the tumor.
PMID- 28400522
TI - Reply to Joly: Inferring causation from comprehensive analysis of observation.
PMID- 28400523
TI - Baseball and jet lag: Correlation does not imply causation.
PMID- 28400524
TI - Women's healthcare consultations on operations: a multidisciplinary provider
questionnaire.
AB - BACKGROUND: 30% of UK primary care consultations relate to gynaecology.
Servicewomen access healthcare in general more frequently than their NHS
counterparts, so military medical professionals are thus more likely to be
managing significant numbers of gynaecological conditions on deployed military
operations. Little is known about their confidence and preparedness in managing
female-specific complaints. This study aimed to assess clinicians' views as to
their training and confidence in managing gynaecological conditions; to gauge the
need for developing treatment guidelines and specific training opportunities and
to establish the frequency and scope of female-specific presentations on a
military deployment. METHOD: A retrospective questionnaire-based service
evaluation of clinical practice was undertaken via an anonymised questionnaire,
which was distributed to 44 randomly selected Afghanistan-based UK military
medical professionals in May 2014. All clinicians with sick parade duties were
eligible for inclusion. RESULTS: 23 (57.5%) military medical professionals
reported managing one or more gynaecological conditions per month while deployed
and 4 (25%) doctors treated more than 5 per month. Of those questioned, 21
(52.5%) felt underprepared to manage gynaecological conditions confidently. Two
thirds would attend a short course on the subject, 13 (32.5%) thought gynaecology
should be included in medical predeployment training (PDT) and 26 (65%) wanted
management guidelines included within Clinical Guidelines for Operations (CGOs).
CONCLUSIONS: Military medical professionals treat servicewomen with
gynaecological problems on deployment. Half of the medical professionals
questioned felt they had insufficient training and experience to do so
confidently. Training packages, as part of PDT or stand alone, were reported as
acceptable methods of improving confidence and knowledge. The common
gynaecological acute presentations were suggested as topics to be included in
CGOs.
PMID- 28400525
TI - Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress.
AB - A crucial step in the life cycle of Plasmodium parasites is the transition from
the liver stage to the blood stage. Hepatocyte-derived merozoites reach the blood
vessels of the liver inside host cell-derived vesicles called merosomes. The
molecular basis of merosome formation is only partially understood. Here we show
that Plasmodium berghei liver stage merozoites, upon rupture of the
parasitophorous vacuole membrane, destabilize the host cell membrane (HCM) and
induce separation of the host cell actin cytoskeleton from the HCM. At the same
time, the phospholipid and protein composition of the HCM appears to be
substantially altered. This includes the loss of a phosphatidylinositol 4,5
bisphosphate (PIP2) reporter and the PIP2-dependent actin-plasma membrane linker
ezrin from the HCM. Furthermore, transmembrane domain-containing proteins and
palmitoylated and myristoylated proteins, as well as glycosylphosphatidylinositol
anchored proteins, lose their HCM localization. Collectively, these findings
provide an explanation of HCM destabilization during Plasmodium liver stage
egress and thereby contribute to our understanding of the molecular mechanisms
that lead to merosome formation.IMPORTANCE Egress from host cells is an essential
process for intracellular pathogens, allowing successful infection of other cells
and thereby spreading the infection. Here we describe the molecular details of a
novel egress strategy of Plasmodium parasites infecting hepatocytes. We show that
toward the end of the liver stage, parasites induce a breakdown of the host cell
actin cytoskeleton, leading to destabilization of the host cell plasma membrane.
This, in turn, results in the formation of membrane vesicles (merosomes), in
which parasites can safely migrate from liver tissue to the bloodstream to infect
red blood cells and start the pathogenic phase of malaria.
PMID- 28400526
TI - Plasmodium falciparum K13 Mutations Differentially Impact Ozonide Susceptibility
and Parasite Fitness In Vitro.
AB - The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to
artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based
combination therapies (ACTs), underscore the urgent need to identify suitable
replacement drugs. Discovery and development efforts have identified a series of
ozonides with attractive chemical and pharmacological properties that are being
touted as suitable replacements. Partial resistance to ART, defined as delayed
parasite clearance in malaria patients treated with an ART derivative or an ACT,
has been associated with mutations in the P. falciparum K13 gene. In light of
reports showing that ART derivatives and ozonides share similar modes of action,
we have investigated whether parasites expressing mutant K13 are cross-resistant
to the ozonides OZ439 (artefenomel) and OZ227 (arterolane). This work used a
panel of culture-adapted clinical isolates from Cambodia that were genetically
edited to express variant forms of K13. Phenotypic analyses employed ring-stage
survival assays (ring-stage survival assay from 0 to 3 h [RSA0-3h]), whose
results have earlier been shown to correlate with parasite clearance rates in
patients. Our results document cross-resistance between OZ277 and
dihydroartemisinin (DHA), a semisynthetic derivative of ART, in parasites
carrying the K13 mutations C580Y, R539T, and I543T. For OZ439, we observed cross
resistance only for parasites that carried the rare K13 I543T mutation, with no
evidence of cross-resistance afforded by the prevalent C580Y mutation. Mixed
culture competition experiments with isogenic lines carrying modified K13
revealed variable growth deficits depending on the K13 mutation and parasite
strain and provide a rationale for the broad dissemination of the fitness-neutral
K13 C580Y mutation throughout strains currently circulating in Southeast
Asia.IMPORTANCE ACTs have helped halve the malaria disease burden in recent
years; however, emerging resistance to ART derivatives threatens to reverse this
substantial progress. Resistance is driven primarily by mutations in the P.
falciparum K13 gene. These mutations pose a threat to ozonides, touted as
promising alternatives to ARTs that share a similar mode of action. We report
that DHA was considerably more potent than OZ439 and OZ277 against ART-sensitive
asexual blood-stage parasites cultured in vitro We also document that mutant K13
significantly compromised the activity of the registered drug OZ277. In contrast,
OZ439 remained effective against most parasite lines expressing mutant K13, with
the exception of I543T that merits further monitoring in field-based OZ439
efficacy studies. K13 mutations differed considerably in their impact on parasite
growth rates, in a strain-dependent context, with the most prevalent C580Y
mutation being fitness neutral in recently culture-adapted strains from Cambodia,
the epicenter of emerging ART resistance.
PMID- 28400527
TI - Targeting Energy Metabolism in Mycobacterium tuberculosis, a New Paradigm in
Antimycobacterial Drug Discovery.
AB - Drug-resistant mycobacterial infections are a serious global health challenge,
leading to high mortality and socioeconomic burdens in developing countries
worldwide. New innovative approaches, from identification of new targets to
discovery of novel chemical scaffolds, are urgently needed. Recently, energy
metabolism in mycobacteria, in particular the oxidative phosphorylation pathway,
has emerged as an object of intense microbiological investigation and as a novel
target pathway in drug discovery. New classes of antibacterials interfering with
elements of the oxidative phosphorylation pathway are highly active in combating
dormant or latent mycobacterial infections, with a promise of shortening
tuberculosis chemotherapy. The regulatory approval of the ATP synthase inhibitor
bedaquiline and the discovery of Q203, a candidate drug targeting the cytochrome
bc1 complex, have highlighted the central importance of this new target pathway.
In this review, we discuss key features and potential applications of inhibiting
energy metabolism in our quest for discovering potent novel and sterilizing drug
combinations for combating tuberculosis. We believe that the combination of drugs
targeting elements of the oxidative phosphorylation pathway can lead to a
completely new regimen for drug-susceptible and multidrug-resistant tuberculosis.
PMID- 28400528
TI - Within-Host Evolution of Burkholderia pseudomallei during Chronic Infection of
Seven Australasian Cystic Fibrosis Patients.
AB - Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung
function decline. CF patients are at an increased risk of respiratory infections,
including those by the environmental bacterium Burkholderia pseudomallei, the
causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei
isolates collected between ~4 and 55 months apart from seven chronically infected
CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns
similar to those of other chronic infections, including emergence of antibiotic
resistance, genome reduction, and deleterious mutations in genes involved in
virulence, metabolism, environmental survival, and cell wall components. We
documented the first reported B. pseudomallei hypermutators, which were likely
caused by defective MutS. Further, our study identified both known and novel
molecular mechanisms conferring resistance to three of the five clinically
important antibiotics for melioidosis treatment. Our report highlights the
exquisite adaptability of microorganisms to long-term persistence in their
environment and the ongoing challenges of antibiotic treatment in eradicating
pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a
degree of predictability in bacterial evolution in the CF lung and potential
targeted eradication of chronic CF infections in the
future.IMPORTANCEBurkholderia pseudomallei, the causative agent of melioidosis,
is an environmental opportunistic bacterium that typically infects
immunocompromised people and those with certain risk factors such as cystic
fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections,
for reasons that are not well understood. This report is the first to describe B.
pseudomallei evolution within the CF lung during chronic infection. We show that
the pathways by which B. pseudomallei adapts to the CF lung are similar to those
seen in better-studied CF pathogens such as Pseudomonas aeruginosa,
Staphylococcus aureus, and Burkholderia cepacia complex species. Adaptations
include the accumulation of antibiotic resistance, loss of nonessential genes,
metabolic alterations, and virulence factor attenuation. Known and novel
mechanisms of resistance to three of the five antibiotics used in melioidosis
treatment were identified. Similar pathways of evolution in CF pathogens,
including B. pseudomallei, provide exciting avenues for more-targeted treatment
of chronic, recalcitrant infections.
PMID- 28400530
TI - Phototaxis of Cyanobacteria under Complex Light Environments.
AB - Photosynthetic bacteria are capable of producing their own food via
photosynthesis. Unsurprisingly, they evolved the ability to move toward better
light conditions (i.e., phototaxis). In a recent article in mBio, Chau et al.
tuned the wavelength, flux, direction, and timing of light input and
characterized the motility of the unicellular cyanobacterium Synechocystis sp.
strain PCC6803 (R. M. W. Chau, D. Bhaya, and K. C. Huang, mBio 8:e02330-16, 2017,
https://doi.org/10.1128/mBio.02330-16). The results revealed an intricate
dependence of the motility on various light inputs, laying the fundamental
groundwork toward understanding phototaxis under complex and dynamic light
environments.
PMID- 28400529
TI - Control of gdhR Expression in Neisseria gonorrhoeae via Autoregulation and a
Master Repressor (MtrR) of a Drug Efflux Pump Operon.
AB - The MtrCDE efflux pump of Neisseria gonorrhoeae contributes to gonococcal
resistance to a number of antibiotics used previously or currently in treatment
of gonorrhea, as well as to host-derived antimicrobials that participate in
innate defense. Overexpression of the MtrCDE efflux pump increases gonococcal
survival and fitness during experimental lower genital tract infection of female
mice. Transcription of mtrCDE can be repressed by the DNA-binding protein MtrR,
which also acts as a global regulator of genes involved in important metabolic,
physiologic, or regulatory processes. Here, we investigated whether a gene
downstream of mtrCDE, previously annotated gdhR in Neisseria meningitidis, is a
target for regulation by MtrR. In meningococci, GdhR serves as a regulator of
genes involved in glucose catabolism, amino acid transport, and biosynthesis,
including gdhA, which encodes an l-glutamate dehydrogenase and is located next to
gdhR but is transcriptionally divergent. We report here that in N. gonorrhoeae,
expression of gdhR is subject to autoregulation by GdhR and direct repression by
MtrR. Importantly, loss of GdhR significantly increased gonococcal fitness
compared to a complemented mutant strain during experimental murine infection.
Interestingly, loss of GdhR did not influence expression of gdhA, as reported for
meningococci. This variance is most likely due to differences in promoter
localization and utilization between gonococci and meningococci. We propose that
transcriptional control of gonococcal genes through the action of MtrR and GdhR
contributes to fitness of N. gonorrhoeae during infection.IMPORTANCE The
pathogenic Neisseria species are strict human pathogens that can cause a sexually
transmitted infection (N. gonorrhoeae) or meningitis or fulminant septicemia (N.
meningitidis). Although they share considerable genetic information, little
attention has been directed to comparing transcriptional regulatory systems that
modulate expression of their conserved genes. We hypothesized that
transcriptional regulatory differences exist between these two pathogens, and we
used the gdh locus as a model to test this idea. For this purpose, we studied two
conserved genes (gdhR and gdhA) within the locus. Despite general conservation of
the gdh locus in gonococci and meningococci, differences exist in noncoding
sequences that correspond to promoter elements or potential sites for interacting
with DNA-binding proteins, such as GdhR and MtrR. Our results indicate that
implications drawn from studying regulation of conserved genes in one pathogen
are not necessarily translatable to a genetically related pathogen.
PMID- 28400531
TI - Genomics and evolution of protein phosphatases.
AB - Protein phosphatases are the essential opposite to protein kinases; together,
these enzymes regulate all protein phosphorylation and most cellular processes.
To better understand the global roles of protein phosphorylation, we cataloged
the human protein phosphatome, composed of 189 known and predicted human protein
phosphatase genes. We also identified 79 protein phosphatase pseudogenes or
retrogenes, some of which may have residual function. We traced the origin and
diversity of phosphatases by building protein phosphatomes for eight other
eukaryotes, from the protist Dictyostelium to the sea urchin. We classified
protein phosphatases from all nine species into a hierarchy of 10 protein folds,
21 families, and 178 subfamilies. We found that >80% of the 101 human subfamilies
were conserved across the animal kingdom, but show substantial differences in
evolution, including losses and expansions of individual subfamilies and changes
in accessory domains. Protein phosphatases show similar evolutionary dynamics to
those of kinases, with substantial losses in major model organisms. Sequence
analysis predicts that 26 human protein phosphatase domains are catalytically
disabled and that this disability is mostly conserved across orthologs. This
genomic and evolutionary perspective on protein phosphatases provides a framework
for global analysis of protein phosphorylation throughout the animal kingdom.
PMID- 28400535
TI - Hippo-sized antiviral defenses.
AB - The Hippo signaling pathway modulates the strength of antiviral responses
according to nutritional status or cell density.
PMID- 28400536
TI - NLS protects DNA damage protein.
AB - A single motif targets a protein to the nucleus and directs its deubiquitylation,
promoting high-fidelity DNA damage repair.
PMID- 28400538
TI - The transcription factor MAFK induces EMT and malignant progression of triple
negative breast cancer cells through its target GPNMB.
AB - Triple-negative breast cancer (TNBC) is particularly aggressive and difficult to
treat. For example, the transforming growth factor-beta (TGF-beta) pathway is
implicated in TNBC progression and metastasis, but its opposing role in tumor
suppression in healthy tissues and early-stage lesions makes it a challenging
target. Therefore, additional molecular characterization of TNBC may lead to
improved patient prognosis by informing the development and optimum use of
targeted therapies. We found that musculoaponeurotic fibrosarcoma (MAF) oncogene
family protein K (MAFK), a member of the small MAF family of transcription
factors that are induced by the TGF-beta pathway, was abundant in human TNBC and
aggressive mouse mammary tumor cell lines. MAFK promoted tumorigenic growth and
metastasis by 4T1 cells when implanted subcutaneously in mice. Overexpression of
MAFK in mouse breast epithelial NMuMG cells induced epithelial-mesenchymal
transition (EMT) phenotypes and promoted tumor formation and invasion in mice.
MAFK induced the expression of the gene encoding the transmembrane glycoprotein
nmb (GPNMB). Similar to MAFK, GPNMB overexpression in NMuMG cells induced EMT,
tumor formation, and invasion, in mice, whereas knockdown of MAFK in tumor cells
before implantation suppressed tumor growth and progression. MAFK and GPNMB
expression correlated with poor prognosis in TNBC patients. These findings
suggest that MAFK and its target gene GPNMB play important roles in the malignant
progression of TNBC cells, offering potentially new therapeutic targets for TNBC
patients.
PMID- 28400537
TI - YAP-mediated mechanotransduction determines the podocyte's response to damage.
AB - Podocytes are terminally differentiated cells of the kidney filtration barrier.
They are subjected to physiological filtration pressure and considerable
mechanical strain, which can be further increased in various kidney diseases.
When injury causes cytoskeletal reorganization and morphological alterations of
these cells, the filtration barrier may become compromised and allow proteins to
leak into the urine (a condition called proteinuria). Using time-resolved
proteomics, we showed that podocyte injury stimulated the activity of the
transcriptional coactivator YAP and the expression of YAP target genes in a rat
model of glomerular disease before the development of proteinuria. Although the
activities of YAP and its ortholog TAZ are activated by mechanical stress in most
cell types, injury reduced YAP and TAZ activity in cultured human and mouse
podocyte cell lines grown on stiff substrates. Culturing these cells on soft
matrix or inhibiting stress fiber formation recapitulated the damage-induced YAP
up-regulation observed in vivo, indicating a mechanotransduction-dependent
mechanism of YAP activation in podocytes. YAP overexpression in cultured
podocytes increased the abundance of extracellular matrix-related proteins that
can contribute to fibrosis. YAP activity was increased in mouse models of
diabetic nephropathy, and the YAP target CTGF was highly expressed in renal
biopsies from glomerular disease patients. Although overexpression of human YAP
in mice induced mild proteinuria, pharmacological inhibition of the interaction
between YAP and its partner TEAD in rats ameliorated glomerular disease and
reduced damage-induced mechanosignaling in the glomeruli. Thus, perturbation of
YAP-dependent mechanosignaling is a potential therapeutic target for treating
some glomerular diseases.
PMID- 28400539
TI - Mass cytometry deep phenotyping of human mononuclear phagocytes and myeloid
derived suppressor cells from human blood and bone marrow.
AB - The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and
dendritic cell (DC) populations that are heterogeneous, both phenotypically and
functionally. In this study, we sought to characterize those diverse MPS
phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of
monocytes, macrophages, and DCs, a panel was designed to measure 38 identity,
activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206,
CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274. MPS diversity was
characterized for 1) circulating monocytes from healthy donors, 2) monocyte
derived macrophages further polarized in vitro (i.e., M-CSF, GM-CSF, IL-4, IL-10,
IFN-gamma, or LPS long-term stimulations), 3) monocyte-derived DCs, and 4)
myeloid-derived suppressor cells (MDSCs), generated in vitro from bone marrow
and/or peripheral blood. Known monocyte subsets were detected in peripheral blood
to validate the panel and analysis pipeline. Then, using various culture
conditions and stimuli before CyTOF analysis, we constructed a multidimensional
framework for the MPS compartment, which was registered against historical M1 or
M2 macrophages, monocyte subsets, and DCs. Notably, MDSCs generated in vitro from
bone marrow expressed more S100A9 than when generated from peripheral blood.
Finally, to test the approach in vivo, peripheral blood from patients with
melanoma (n = 5) was characterized and observed to be enriched for MDSCs with a
phenotype of CD14+HLA-DRlowS100A9high (3% of PBMCs in healthy donors, 15.5% in
patients with melanoma, P < 0.02). In summary, mass cytometry comprehensively
characterized phenotypes of human monocyte, MDSC, macrophage, and DC
subpopulations in both in vitro models and patients.
PMID- 28400541
TI - Correction: Salvage therapy or simplification of salvage regimens with
dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART
experienced subjects: an Italian cohort.
PMID- 28400542
TI - [Musculoskeletal Tumor].
PMID- 28400543
TI - [I. Identification of a Possible Therapeutic Target for Chondrosarcoma with IDH
Mutant Inhibitors].
PMID- 28400540
TI - CD56bright NK IL-7Ralpha expression negatively associates with HCV level, and IL
7-induced NK function is impaired during HCV and HIV infections.
AB - Several lines of evidence support the concept that NK cells play an important
role in control of hepatitis C virus (HCV) infection via cytokine secretion and
cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development,
activation, proliferation, and cytokine secretion. The IL-7Ralpha chain [cluster
of differentiation (CD)127] is expressed on NK cells, with greatest abundance on
the CD56brightCD16dim/- (CD56bright) subset. Here, we measured CD127 expression
on CD56bright, CD56dimCD16+ (CD56dim), or CD56negCD16+ (CD56neg) NK cell subsets
of 25 uninfected donors (UD); 34 chronic HCV-infected, treatment-naive; 25 HIV
infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV-HIV
coinfected subjects on ART. Interestingly, CD127 expression on CD56bright NK
cells negatively correlated with HCV plasma levels in HCV monoinfection and HCV
HIV coinfection. IL-7 induced CD69 expression, as well as IFN-gamma production,
in CD56bright NK cells and also enhanced the IFN-alpha-induced CD69 expression on
these cells. The latter was impaired in HIV infection. Furthermore, IL-7 induced
B cell lymphoma 2 (BCL-2) expression and cell cycling of CD56bright NK cells, and
this effect was impaired in HCV- and HIV-infected subjects. Whereas IL-7
stimulated CD56bright NK cell degranulation appeared intact in all cohorts, we
observed impaired IL-7-activated NK cell cytolytic function in HCV- and HIV
infected subjects. Finally, IL-7-induced phosphorylation of STAT-5 (pSTAT-5)
signaling was impaired in NK cells of subjects with chronic viral infection, and
this was reversible upon 6 mo of viral suppression with IFN-free HCV therapy.
These results implicate that IL-7-dependent NK cell activation and effector
function may be other host immune surveillance mechanisms that are impaired in
viral infections.
PMID- 28400544
TI - [II. Targeting Epigenetics in Treatment of Cancer and Sarcoma].
PMID- 28400545
TI - [III. Recent Clinical Development of Cancer Immunotherapy and Speculation for
Bone and Soft Tissue Tumors].
PMID- 28400546
TI - Management of bleeding or urgent interventions in patients treated with direct
oral anticoagulants: 2017 recommendations for Poland.
AB - Direct oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, and
rivaroxaban are mainly used in the prevention of thromboembolic complications in
patients with atrial fibrillation (AF) and in the treatment of venous
thromboembolism. As compared with vitamin K antagonists (VKAs), they are
characterized by at least similar efficacy and better safety profiles, especially
with respect to intracranial hemorrhages. Moreover, they are more convenient
therapeutic agents. The 2016 European Society of Cardiology guidelines clearly
favor DOACs over VKAs in patients with AF. However, DOAC therapy is also
associated with the risk of bleeding complications. The aim of this review was to
provide recommendations for the management of bleeding complications during DOAC
therapy in the Polish setting. The recommendations were based on the most
important documents concerning this issue and were developed by representatives
of different medical specialties. Experience in managing cases of bleeding on
DOAC therapy is still limited. Therefore, we hope that this publication will be
helpful in everyday clinical practice and that it will be useful for developing
in-hospital recommendations for the management of patients with DOAC-related
bleeding.
PMID- 28400547
TI - Anemia in thyroid diseases.
AB - Anemia is a frequent, although often underestimated, clinical condition
accompanying thyroid diseases. Despite the fact that anemia and thyroid
dysfunction often occur simultaneously, the causative relationship between the
disorders remains ambiguous. Thyroid hormones stimulate the proliferation of
erythrocyte precursors both directly and via erythropoietin production
enhancement, while iron-deficient anemia negatively influences thyroid hormone
status. Thus, different forms of anemia might develop in the course of thyroid
dysfunction. Normocytic anemia is the most common, while macrocytic or microcytic
anemia occurs less frequently. Anemia in hypothyroidism might result from bone
marrow depression, decreased erythropoietin production, comorbid diseases, or
concomitant iron, vitamin B12, or folate deficiency. Altered iron metabolism and
oxidative stress may contribute to anemia in hyperthyroidism. The risk of anemia
in autoimmune thyroid disease (AITD) may be related to pernicious anemia and
atrophic gastritis, celiac disease, autoimmune hemolytic syndrome, or rheumatic
disorders. The coexistence of anemia and thyroid disease constitutes an important
clinical problem. Thus, the aim of this review was to provide a comprehensive
summary of data on the prevalence, potential mechanisms, and therapy of anemia in
the course of thyroid diseases from the clinical and pathogenetic perspectives.
Thyroid dysfunction and AITD should be considered in a differential diagnosis of
treatment-resistant or refractory anemia, as well as in the case of increased red
blood cell distribution width. Of note, the presence of AITD itself,
independently from thyroid hormone status, might affect the hemoglobin level.
PMID- 28400548
TI - The relation between cultural values, euthanasia, and spiritual care in the
Netherlands.
AB - The aim of this paper is to gain some understanding of euthanasia as a Dutch
cultural practice, focusing on value orientations that lie beneath the surface of
what is made visible in the many national surveys done in the Netherlands. In
order to reach this aim, I take 2 steps. In the first place, I give a short
sketch of euthanasia as it is understood and practiced in the Netherlands. This
is followed by a cultural analysis by the American-Dutch historian James Kennedy
who studied the euthanasia debate in the Netherlands from the 1960s until 1985.
Having arrived at some cultural understanding of Dutch mentality, I dive deeper
into the understanding of the Dutch value orientations by focusing on the
dimension of spiritual care at the end of life. After having defined the concept
of spirituality, I sketch the contemporary state of affairs in this area and
report how spiritual care in the Netherlands is understood and practiced by
discussing the consensus-based Dutch guideline on spiritual care in palliative
care, recent research on hope among palliative care patients in the Netherlands,
and an often used Dutch tool for spiritual care: the Ars moriendi model. I end
this contribution by sketching how I think that spiritual care at the end of life
should be developed further in the Netherlands from a palliative care
perspective.
PMID- 28400550
TI - Primary Pituitary Tuberculosis Revisited.
AB - BACKGROUND Primary pituitary tuberculosis (in absence of other organ involvement
and constitutional symptoms) is an extremely rare disease with total reported
cases in the literature fewer than a hundred. Misdiagnosis as pituitary adenoma
is common and late diagnosis can result in a permanent endocrine dysfunction
and/or long-term neurologic sequelae. CASE REPORT We report on the case of a
middle-aged woman who presented with severe headache and left third cranial nerve
palsy. Magnetic resonance imaging (MRI) revealed a large pituitary tumor invading
the left cavernous sinus. The case was initially misdiagnosed as pituitary
adenoma. A pituitary biopsy was performed and was suggestive of pituitary
tuberculosis. Extensive radiologic investigations did not reveal any evidence of
other organ involvement by tuberculosis. She was successfully treated with anti
tuberculous medications. CONCLUSIONS In areas with a high pre-test probability of
tuberculosis, pituitary tuberculosis should be included in the differential
diagnosis of pituitary tumors in order to avoid unnecessary surgical
interventions. Besides being the first histologically-proven primary pituitary
tuberculosis case reported from Qatar, the current case is unique in that
extensive radiologic investigations did not reveal any evidence of other systemic
or pulmonary tuberculosis.
PMID- 28400549
TI - Associations of Prostate-Specific Antigen, Prostate Carcinoma Tissue Gleason
Score, and Androgen Receptor Expression with Bone Metastasis in Patients with
Prostate Carcinoma.
AB - BACKGROUND Prostate carcinoma (PCa) is often not diagnosed until advanced disease
with bone metastasis. Predictive factors for bone metastasis are required to
improve patient outcomes. The study aimed to analyze the factors associated with
bone metastases in newly diagnosed patients with PCa. MATERIAL AND METHODS This
was a retrospective study of 80 patients newly diagnosed with PCa by pathological
examination between January 2012 and December 2014. Bone metastases were
diagnosed by positron emission computed tomography. Clinical data, serological
laboratory results, and pathological examination results were collected. RESULTS
Among the 80 patients, 45 (56%) had bone metastases. Age, serum alkaline
phosphatase, prostate-specific antigen (PSA), erythrocyte sedimentation rate, PCa
tissue Gleason score, androgen receptor (AR) expression, and Ki-67 expression
were higher in patients with bone metastasis compared with those without (all
P<0.05). Multivariate logistic regression showed that PSA (OR: 1.005; 95%CI:
1.001-1.010; P=0.016), Gleason score (OR: 4.095; 95%CI: 1.592-10.529; P=0.003),
and AR expression (OR: 14.023; 95%CI: 3.531-55.6981; P=0.005) were independently
associated with bone metastases. Cut-off values for PSA, Gleason score, and AR
expression were 67.1 ng/ml (sensitivity: 55.6%; specificity: 97.1%), 7.5
(sensitivity: 75.6%; specificity: 82.9%), and 2.5 (sensitivity: 84.0%;
specificity: 91.4%), respectively. CONCLUSIONS PSA, Gleason score, and AR
expression in PCa tissues were independently associated with PCa bone metastases.
These results could help identifying patients with PCa at high risk of bone
metastases.
PMID- 28400551
TI - Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of
eight GWASs in the TRICL-ILCCO consortium.
AB - The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling
events mediated by TCPTP. Mutations and genetic variants of some genes in the
TCPTP pathway are associated with lung cancer risk and survival. In the present
study, we first investigated associations of 5,162 single nucleotide
polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by
using summary data of six published genome-wide association studies (GWAS) of
12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight
genes after correction for multiple comparisons by a false discovery rate <0.20.
Then, we performed in silico functional analyses for these 11 SNPs by eQTL
analysis, two of which, PTPN2 SNPs rs2847297 and rs2847282, were chosen as
tagSNPs. We further included two additional GWAS datasets of Harvard University
(984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls), and
the overall effects of these two SNPs among all eight GWAS studies remained
significant (OR = 0.95, 95% CI = 0.92-0.98, and P = 0.004 for rs2847297; OR =
0.95, 95% CI = 0.92-0.99, and P = 0.009 for rs2847282). In conclusion, the PTPN2
rs2847297 and rs2847282 may be potential susceptible loci for lung cancer risk.
PMID- 28400552
TI - Kinetic CRAC uncovers a role for Nab3 in determining gene expression profiles
during stress.
AB - RNA-binding proteins play a key role in shaping gene expression profiles during
stress, however, little is known about the dynamic nature of these interactions
and how this influences the kinetics of gene expression. To address this, we
developed kinetic cross-linking and analysis of cDNAs (chiCRAC), an ultraviolet
cross-linking method that enabled us to quantitatively measure the dynamics of
protein-RNA interactions in vivo on a minute time-scale. Here, using chiCRAC we
measure the global RNA-binding dynamics of the yeast transcription termination
factor Nab3 in response to glucose starvation. These measurements reveal rapid
changes in protein-RNA interactions within 1 min following stress imposition.
Changes in Nab3 binding are largely independent of alterations in transcription
rate during the early stages of stress response, indicating orthogonal
transcriptional control mechanisms. We also uncover a function for Nab3 in
dampening expression of stress-responsive genes. chiCRAC has the potential to
greatly enhance our understanding of in vivo dynamics of protein-RNA
interactions.Protein RNA interactions are dynamic and regulated in response to
environmental changes. Here the authors describe 'kinetic CRAC', an approach that
allows time resolved analyses of protein RNA interactions with minute time point
resolution and apply it to gain insight into the function of the RNA-binding
protein Nab3.
PMID- 28400553
TI - Efficacy and safety of tacrolimus treatment for neuromyelitis optica spectrum
disorder.
AB - Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory
autoimmune disease that mainly involves the optic nerves and spinal cord, causing
blindness and paralysis. Although some immunosuppressants such as rituximab and
azathioprine have proven to be effective in relapse prevention, the high costs or
intolerable adverse events preclude their wide application. Thus, we have
conducted a retrospective study in 25 NMOSD patients who were treated with
tacrolimus, an immunosuppressant with high efficacy and good tolerance in other
autoimmune diseases, to assess its efficacy and safety in NMOSD treatment during
the last five years (2011-2016). The results revealed that tacrolimus could
reduce the relapse rate by 86.2% and improve the Expanded Disability Status Scale
(EDSS) scores (4.5 vs 2.3; P < 0.001) significantly. Relapses in tacrolimus
treatment were associated with serum titers of aquaporin 4 antibody (AQP4-IgG) (P
= 0.028). Further Cox proportional analysis demonstrated that patients with high
titers of AQP4-IgG (>=1:64) had a significantly higher risk of relapse than those
with low titers after tacrolimus therapy (HR:5.665; CI95: 1.012-31.705; P =
0.048). Tacrolimus tended to be superior to azathioprine (29 patients) in terms
of efficacy and safety during the same period. Our study suggests that tacrolimus
may be another promising immunosuppressant for NMOSD.
PMID- 28400554
TI - Essential turmeric oils enhance anti-inflammatory efficacy of curcumin in dextran
sulfate sodium-induced colitis.
AB - Turmeric has been used as a medicinal herb for thousands of years for treatment
of various disorders. Although curcumin is the most studied active constituents
of turmeric, accumulating evidence suggests that other components of turmeric
have additional anti-inflammatory and anti-tumorigenic properties. Herein, we
investigated anti-inflammatory efficacy and associated gene expression
alterations of a specific, curcumin preparation containing essential turmeric
oils (ETO-curcumin) in comparison to standard curcumin at three specific doses
(0, 5, 25 or 50 mg/kg), in an animal model of dextran sodium sulfate (DSS)
induced colitis. The present study showed that both ETO and standard curcumin
treatments provided protection against DSS-induced inflammation. However, ETO
curcumin improved disease activity index (DAI) dose-dependently, while the anti
inflammatory efficacy of standard curcumin remained constant, suggesting that ETO
curcumin may provide superior anti-inflammatory efficacy compared to standard
curcumin. Gene expression analysis revealed that anti-inflammatory cytokines
including IL-10 and IL-11 as well as FOXP3 were upregulated in the colon by ETO
curcumin. Collectively, these findings suggest that the combined treatment of
curcumin and essential turmeric oils provides superior protection from DSS
induced colitis than curcumin alone, highlighting the anti-inflammatory potential
of turmeric.
PMID- 28400555
TI - Flexible metal-semiconductor-metal device prototype on wafer-scale thick boron
nitride layers grown by MOVPE.
AB - Practical boron nitride (BN) detector applications will require uniform materials
over large surface area and thick BN layers. To report important progress toward
these technological requirements, 1~2.5 um-thick BN layers were grown on 2-inch
sapphire substrates by metal-organic vapor phase epitaxy (MOVPE). The structural
and optical properties were carefully characterized and discussed. The thick
layers exhibited strong band-edge absorption near 215 nm. A highly oriented two
dimensional h-BN structure was formed at the film/sapphire interface, which
permitted an effective exfoliation of the thick BN film onto other adhesive
supports. And this structure resulted in a metal-semiconductor-metal (MSM) device
prototype fabricated on BN membrane delaminating from the substrate. MSM
photodiode prototype showed low dark current of 2 nA under 100 V, and 100 +/- 20%
photoconductivity yield for deep UV light illumination. These wafer-scale MOVPE
grown thick BN layers present great potential for the development of deep UV
photodetection applications, and even for flexible (opto-) electronics in the
future.
PMID- 28400556
TI - Precise treatment of aortic aneurysm by three-dimensional printing and simulation
before endovascular intervention.
AB - In this study, three-dimensional printing (3Dp) models and simulation surgeries
(SSs) were applied in two challenging aortic cases. The first was an abdominal
aortic aneurysm with a complex neck, and the second was a thoracic aortic
dissection aneurysm (TADA) with an angled arch. In order to avoid unpredictable
obstacles and difficulties, we made optimal surgical plans by using 3D models and
virtual simulations. Based on preoperative evaluation system, the surgical plans
seemed more reasonable and time-saving.
PMID- 28400557
TI - Chemical Bonding and sigma-Aromaticity in Charged Molecular Alloys: [Pd2As14]4-
and [Au2Sb14]4- Clusters.
AB - We report a computational study on the structures and bonding of a charged
molecular alloy D 2h [Pd2As14]4- (1), as well as a model D 2h [Au2Sb14]4- (2)
cluster. Our effort makes use of an array of quantum chemistry tools: canonical
molecular orbital analysis, adaptive natural density partitioning, natural bond
orbital analysis, orbital composition analysis, and nucleus independent chemical
shift calculations. Both clusters consist of two X7 (X = As, Sb) cages, which are
interconnected via a M2 (M = Pd, Au) dumbbell, featuring two distorted square
planar MX4 units. Excluding the Pd/As or Au/Sb lone-pairs, clusters 1 and 2 are
50- and 44-electron systems, respectively, of which 32 electrons are for two
center two-electron (2c-2e) As-As or Sb-Sb sigma bonds and an additional 16
electrons in 1 for 2c-2e Pd-As sigma bonds. No covalent Pd-Pd or Au-Au bond is
present in the systems. Cluster 1 is shown to possess two globally delocalized
sigma electrons, whereas 2 has two sigma sextets (each associated with an AuSb4
fragment). Thus, 1 and 2 conform to the (4n + 2) Huckel rule, for n = 0 and 1,
respectively, rendering them sigma-aromaticity.
PMID- 28400558
TI - A universal primer-independent next-generation sequencing approach for
investigations of norovirus outbreaks and novel variants.
AB - Norovirus (NoV) is the most common cause of non-bacterial gastroenteritis and is
a major agent associated with outbreaks of gastroenteritis. Conventional
molecular genotyping analysis of NoV, used for the identification of transmission
routes, relies on standard typing methods (STM) by Sanger-sequencing of only a
limited part of the NoV genome, which could lead to wrong conclusions. Here, we
combined a NoV capture method with next generation sequencing (NGS), which
increased the proportion of norovirus reads by ~40 fold compared to NGS without
prior capture. Of 15 NoV samples from 6 single-genotype outbreaks, near full
genome coverage (>90%) was obtained from 9 samples. Fourteen polymerase (RdRp)
and 15 capsid (cap) genotypes were identified compared to 12 and 13 for the STM,
respectively. Analysis of 9 samples from two mixed-genotype outbreaks identified
6 RdRp and 6 cap genotypes (two at >90% NoV genome coverage) compared to 4 and 2
for the STM, respectively. Furthermore, complete or partial sequences from the P2
hypervariable region were obtained from 7 of 8 outbreaks and a new NoV
recombinant was identified. This approach could therefore strengthen outbreak
investigations and could be applied to other important viruses in stool samples
such as hepatitis A and enterovirus.
PMID- 28400559
TI - Knockdown of Broad-Complex Gene Expression of Bombyx mori by Oligopyrrole
Carboxamides Enhances Silk Production.
AB - Bombyx mori (B. mori) is important due to its major role in the silk production.
Though DNA binding ligands often influence gene expression, no attempt has been
made to exploit their use in sericulture. The telomeric heterochromatin of B.
mori is enriched with 5'-TTAGG-3' sequences. These sequences were also found to
be present in several genes in the euchromatic regions. We examined three
synthetic oligopyrrole carboxamides that target 5'-TTAGG-3' sequences in
controlling the gene expression in B. mori. The ligands did not show any defect
or feeding difference in the larval stage, crucial for silk production. The
ligands caused silencing of various isoforms of the broad-complex transcription
factor and cuticle proteins which resulted in late pupal developmental defects.
Furthermore, treatment with such drugs resulted in statistically enhanced cocoon
weight, shell weight, and silk yield. This study shows for the first time use of
oligopyrrole carboxamide drugs in controlling gene expression in B. mori and
their long term use in enhancing silk production.
PMID- 28400560
TI - TGF-beta induces phosphorylation of phosphatase and tensin homolog: implications
for fibrosis of the trabecular meshwork tissue in glaucoma.
AB - Fundamental cell signaling mechanisms that regulate dynamic remodeling of the
extracellular matrix (ECM) in mechanically loaded tissues are not yet clearly
understood. Trabecular meshwork (TM) tissue in the eye is under constant
mechanical stress and continuous remodeling of ECM is crucial to maintain normal
aqueous humor drainage and intraocular pressure (IOP). However, excessive ECM
remodeling can cause fibrosis of the TM as in primary open-angle glaucoma (POAG)
patients, and is characterized by increased resistance to aqueous humor drainage,
elevated IOP, optic nerve degeneration and blindness. Increased levels of active
transforming growth factor-beta2 (TGF-beta2) in the aqueous humor is the main
cause of fibrosis of TM in POAG patients. Herein, we report a novel finding that,
in TM cells, TGF-beta-induced increase in collagen expression is associated with
phosphorylation of phosphatase and tensin homolog (PTEN) at residues
Ser380/Thr382/383. Exogenous overexpression of a mutated form of PTEN with
enhanced phosphatase activity prevented the TGF-beta-induced collagen expression
by TM cells. We propose that rapid alteration of PTEN activity through changes in
its phosphorylation status could uniquely regulate the continuous remodeling of
ECM in the normal TM. Modulating PTEN activity may have high therapeutic
potential to alleviating the fibrosis of TM in POAG patients.
PMID- 28400561
TI - A hybrid stochastic model of folate-mediated one-carbon metabolism: Effect of the
common C677T MTHFR variant on de novo thymidylate biosynthesis.
AB - Folate-mediated one-carbon metabolism (FOCM) is an interconnected network of
metabolic pathways, including those required for the de novo synthesis of dTMP
and purine nucleotides and for remethylation of homocysteine to methionine. Mouse
models of folate-responsive neural tube defects (NTDs) indicate that impaired de
novo thymidylate (dTMP) synthesis through changes in SHMT expression is causative
in folate-responsive NTDs. We have created a hybrid computational model comprised
of ordinary differential equations and stochastic simulation. We investigated
whether the de novo dTMP synthesis pathway was sensitive to perturbations in FOCM
that are known to be associated with human NTDs. This computational model shows
that de novo dTMP synthesis is highly sensitive to the common MTHFR C677T
polymorphism and that the effect of the polymorphism on FOCM is greater in folate
deficiency. Computational simulations indicate that the MTHFR C677T polymorphism
and folate deficiency interact to increase the stochastic behavior of the FOCM
network, with the greatest instability observed for reactions catalyzed by serine
hydroxymethyltransferase (SHMT). Furthermore, we show that de novo dTMP synthesis
does not occur in the cytosol at rates sufficient for DNA replication, supporting
empirical data indicating that impaired nuclear de novo dTMP synthesis results in
uracil misincorporation into DNA.
PMID- 28400562
TI - Root-mediated sex recognition in a dioecious tree.
AB - Recent studies have demonstrated that plants can determine the identity of
neighbouring roots (e.g., self and non-self, kin and non-kin), but whether they
can discriminate by sex remains an open question. Here, we predict that dioecious
plants can modulate their root performance in response to local root conditions
related to sex. Female and male Populus cathayana cuttings were planted in a
greenhouse in root-owner (one individual without a root neighbour) or root-sharer
pairs (two individuals with roots neighbouring each other) with equal amounts of
nutrients and space per plant in three combinations (females-females, males-males
or females-males); root morphology, biomass and allocation were investigated. P.
cathayana root-sharers altered their root growth in same-sex but not in different
sex combinations. Females enhanced root growth and allocation but decreased root
proliferation (greater diameter with reduced branching and specific root length)
in the presence of a female root neighbour, while males reduced root growth but
increased root morphological proliferation in contact with another male.
Therefore, the effect of a neighbour of the same sex differed from that of a
neighbour of the opposite sex, which suggests that these plants can recognize the
sexual identity of their neighbours.
PMID- 28400563
TI - High Throughput Analysis of Golgi Structure by Imaging Flow Cytometry.
AB - The Golgi apparatus is a dynamic organelle, which regulates the vesicular
trafficking. While cellular trafficking requires active changes of the Golgi
membranes, these are not accompanied by changes in the general Golgi's structure.
However, cellular processes such as mitosis, apoptosis and migration require
fragmentation of the Golgi complex. Currently, these changes are most commonly
studied by basic immunofluorescence and quantified by manual and subjective
classification of the Golgi structure in 100-500 stained cells. Several other
high-throughput methods exist as well, but those are either complicated or do not
provide enough morphological information. Therefore, a simple and informative
high content methodology should be beneficial for the study of Golgi
architecture. Here we describe the use of high-throughput imaging flow cytometry
for quantification of Golgi fragmentation, which provides a simple way to analyze
the changes in an automated, quantitative and non-biased manner. Furthermore, it
provides a rapid and accurate way to analyze more than 50,000 cells per sample.
Our results demonstrate that this method is robust and statistically powerful,
thus, providing a much-needed analytical tool for future studies on Golgi
dynamics, and can be adapted to other experimental systems.
PMID- 28400565
TI - Investigation of spin-orbit torque using current-induced magnetization curve.
AB - Manipulation of magnetization using current-induced torque is crucial for
magnetic recording devices. Recently, the spin-orbit torque (SOT) that emerges in
a ferromagnetic thin film on a heavy metal is focused as a new scheme for
magnetization switching in perpendicularly magnetized systems. Since the SOT
provides a perpendicular effective field to the system, the formation of a
magnetic multiple domain state because of Joule heating is supressed in the
magnetization reversal process. This means that high reliable switching is
possible using the SOT. Here, by utilizing the SOT induced domain stability, we
show that an electrical current directly injected to a perpendicularly magnetized
Pt/Co/Pd system can magnetize itself, that is, current-induced magnetization
process from multi to single domain state. A quantitative determination of the
SOT is performed using the current-induced magnetization curve. The present
results are of great importance as another approach to evaluate the SOT effect,
as well as a demonstration of domain state switching caused by the SOT.
PMID- 28400564
TI - A novel 4-arm DNA/RNA Nanoconstruct triggering Rapid Apoptosis of Triple Negative
Breast Cancer Cells within 24 hours.
AB - Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct,
was designed to simultaneously carry three unmodified SiRNA strands for apoptosis
gene knockout in cancer cells without any assistance from commercial transfection
kits. In brief, a holliday junction structure was intelligently designed to
present one arm with a cell targeting aptamer (AS1411) while the remaining three
arms to carry different SiRNA strands by means of DNA/RNA duplex for inducing
apoptosis in cancer cells. By carrying the three SiRNA strands (AKT, MDM2 and
Survivin) into triple negative breast MDA-MB-231 cancer cells, cell number had
reduced by up to ~82% within 24 hours solely from one single administration of 32
picomoles. In the immunoblotting studies, up-elevation of phosphorylated p53 was
observed for more than 8 hours while the three genes of interest were suppressed
by nearly half by the 4-hour mark upon administration. Furthermore, we were able
to demonstrate high cell selectivity of the nanoconstruct and did not exhibit
usual morphological stress induced from liposomal-based transfection agents. To
the best of the authors' knowledge, this system represents the first of its kind
in current literature utilizing a short and highly customizable holliday DNA
junction to carry SiRNA for apoptosis studies.
PMID- 28400566
TI - Serum Metabolomics Analysis Reveals a Distinct Metabolic Profile of Patients with
Primary Biliary Cholangitis.
AB - Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease
associated with profound metabolic changes. The purpose of this study was to
identify a distinctive metabolic signature from the training set with 29 PBC
patients, 30 hepatitis B virus (HBV)-caused cirrhosis (HBC) and 41 healthy
controls, and to validate the applicability and stability of the distinctive
model from the validation set with 21 PBC patients, 7 autoimmune hepatitis (AIH)
and 9 HBC. The sera were investigated using high resolution nuclear magnetic
resonance (NMR) and the datasets were analyzed pairwise using pattern recognition
methods. 45 distinguishable metabolites were identified and 15 metabolic pathways
were reprogrammed. The altered metabolic pathways were associated with glucose,
fatty acid and amino acid metabolites. Logistic regression and ROC analysis were
used to establish a diagnostic model with the equated (p) = -12.22-3.46*log(4
hydroxyproline) + 6.62*log(3-hydroxyisovalerate) - 2.44*log(citraconate) -
3.80*log(pyruvate). The area under the curve (AUC) of the optimized model was
0.937 (95% confidence interval (CI): 0.868-0.976) in the training set and 0.890
(95% CI: 0.743-0.969) in the validation set. These results not only revealed the
potential pathogenesis of PBC, but also provided a feasible diagnostic tool for
PBC populations through detection of serum metabolites.
PMID- 28400567
TI - Genetic dissection of yield traits in super hybrid rice Xieyou9308 using both
unconditional and conditional genome-wide association mapping.
AB - With the development and application of super rice breeding, elite rice hybrids
with super high-yielding potential have been widely developed in last decades in
China. Xieyou9308 is one of the most famous super hybrid rice varieties. To
uncover the genetic mechanism of Xieyou9308's high yield potential, a recombinant
inbred line (RIL) population derived from cross of XieqingzaoB and Zhonghui9308
was re-sequenced and investigated on the grain yield (GYD) and its three
component traits, number of panicles per plant (NP), number of filled grains per
panicle (NFGP), and grain weight (GW). Unconditional and conditional genome-wide
association analysis, based on a linear mixed model with epistasis and gene
environment interaction effects, were conducted, using ~0.7 million identified
SNPs. There were six, four, seven, and seven QTSs identified for GYD, NP, NFGP,
and GW, respectively, with accumulated explanatory heritability varying from
43.06% to 48.36%; additive by environment interactions were detected for GYD,
some minor epistases were detected for NP and NFGP. Further, conditional genetic
mapping analysis for GYD given its three components revealed several novel QTSs
associated with yield than that were suppressed in our unconditional mapping
analysis.
PMID- 28400568
TI - Complexity analysis of fNIRS signals in ADHD children during working memory task.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental
disorder in children. Neuroimaging studies have revealed abnormalities of neural
activities in some brain regions, including the frontal cortex, striatum,
cerebellum, and occipital cortex. Recently, some investigators have demonstrated
that nonlinear complexity analysis of neural activity may provide a new index to
indicate ADHD. In the present study, we used the permutation entropy (PE) to
measure the complexity of functional near-infrared spectroscopy (fNIRS) signals
in children with and without ADHD during a working memory task, it was aimed to
investigate the relationship between the PE values and the cortical activations,
and the different PE values between the children with and without ADHD. We found
that PE values exhibited significantly negative correlation with the cortical
activations (r = -0.515, p = 0.003), and the PE values of right dorsolateral
prefrontal cortex in ADHD children were significantly larger than those in normal
controls (p = 0.027). In addition, the PE values of right dorsolateral prefrontal
cortex were positively correlated to the ADHD index (r = 0.448, p = 0.012). These
results suggest that complexity analysis of fNIRS signals could be a promising
tool in diagnosing children with ADHD.
PMID- 28400569
TI - Association between schizophrenia and violence among Chinese female offenders.
AB - Little is known about the association between schizophrenia and violence in women
in China. This study aimed to examine the association between schizophrenia and
violence in Chinese female offenders. Fifty-two schizophrenia patients were
identified from the female offenders who received forensic psychiatric
assessments in 2011 in Hunan province, China. Using a propensity score matching
method, 104 matched controls without psychiatric disorders were selected from
female criminals in Hunan province. Violent offences and homicides were verified
and recorded. The percentages of violent offences and homicides were
significantly higher in female offenders with schizophrenia than in controls
(78.8% vs. 30.8%, P < 0.001; 44.2% vs. 18.3%, P = 0.001, respectively).
Multivariate logistic regression analyses revealed that diagnosis of
schizophrenia, younger age at first offence, living in rural area and a lower
education level were independently and positively associated with violent
offences, while having a diagnosis of schizophrenia and lower education level
were associated with homicides. There appears to be an independent and positive
association between schizophrenia and violent offence in Chinese female
offenders. Effective preventive approaches on violence in female schizophrenia
patients are warranted.
PMID- 28400570
TI - Nano silica diaphragm in-fiber cavity for gas pressure measurement.
AB - We demonstrate an ultrahigh-sensitivity gas pressure sensor based on the Fabry
Perot interferometer employing a fiber-tip diaphragm-sealed cavity. The cavity is
comprised of a silica capillary and ultrathin silica diaphragm with a thickness
of 170 nm, with represents the thinnest silica diaphragm fabricated thus far by
an electrical arc discharge technique. The resulting Fabry-Perot interferometer
based gas pressure sensor demonstrates a gas pressure sensitivity of about 12.22
nm/kPa, which is more than two orders of magnitude greater than that of a
similarly configured fiber-tip air bubble sensor. Moreover, our gas pressure
sensor has a low temperature cross-sensitivity of about 106 Pa/ degrees C, and
the sensor functions well up to a temperature of about 1000 degrees C. As such,
the sensor can potentially be employed in high-temperature environments.
PMID- 28400571
TI - Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves
health and survival in mice.
AB - The tuberous sclerosis complex 1/2 (TSC1/2) is an endogenous regulator of the
mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an
important role in health and aging, the role of TSC1/2 in aging has not been
fully investigated. In the current study, a constitutive TSC1 transgenic (Tsc1 tg
) mouse model was generated and characterized. mTORC1 signaling was reduced in
majority of the tissues, except the brain. In contrast, mTORC2 signaling was
enhanced in Tsc1 tg mice. Tsc1 tg mice are more tolerant to exhaustive exercises
and less susceptible to isoproterenol-induced cardiac hypertrophy at both young
and advanced ages. Tsc1 tg mice have less fibrosis and inflammation in aged as
well as isoproterenol-challenged heart than age-matched wild type mice. The
female Tsc1 tg mice exhibit a higher fat to lean mass ratio at advanced ages than
age-matched wild type mice. More importantly, the lifespan increased
significantly in female Tsc1 tg mice, but not in male Tsc1 tg mice. Collectively,
our data demonstrated that moderate increase of TSC1 expression can enhance
overall health, particularly cardiovascular health, and improve survival in a
gender-specific manner.
PMID- 28400573
TI - Time-decay Memristive Behavior and diffusive dynamics in one forget process
operated by a 3D vertical Pt/Ta2O5-x/W device.
AB - A time-decay resistive switching memory using a 3D vertical Pt/Ta2O5-x/W device
architecture is demonstrated, in which horizontal W electrodes were fabricated,
and vertical Pt electrodes was formed at the sidewall after oxide was deposited.
Unlike conventional resistive switching, which usually form a conductive filament
connect two electrodes, a weak conductive filament was formed from bottom
electrode W to near top electrode Pt. The memory can be recovered with a time
scale when the electrical stimulation is removed. However, different decay
behaviors were observed in one decay curve, including rapid decay and slow decay
processes. This can be a good simulation of different stages of forgetting. By a
combination of the current decay fitting and the conductive analysis, the rapid
decay and slow decay processes correspond to ion diffusion and electron
detrapping, respectively.
PMID- 28400572
TI - Imaging atherosclerosis in rheumatoid arthritis: evidence for increased
prevalence, altered phenotype and a link between systemic and localised plaque
inflammation.
AB - In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased
cardiovascular risk through accelerated atherosclerosis. It may also lead to a
more high-risk plaque phenotype. We sought to investigate carotid plaque
phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCE-MRI) and
Fludeoxyglucose Positron Emission Tomography(FDG-PET). In this pilot study, RA
patients and age/sex-matched controls were evaluated for cardiovascular risk
factors and carotid plaque on ultrasound. Subjects with plaque >2 mm thick
underwent DCE-MRI, and a subgroup of patients had FDG-PET. Comparison of MRI
findings between groups and correlation between clinical, serological markers and
imaging findings was undertaken. 130 patients and 62 controls were recruited.
Plaque was more prevalent in the RA group (53.1% vs 37.0%, p = 0.038) and was
independently associated with IL6 levels (HR[95%CI]: 2.03 [1.26, 3.26] per
quartile). DCE-MRI data were available in 15 patients and 5 controls. Higher
prevalence of plaque calcification was noted in RA, despite similar plaque size
(73.3% vs 20%, p = 0.04). FDG-PET detected plaque inflammation in 12/13 patients
scanned and degree of inflammation correlated with hs-CRP (r = 0.58, p = 0.04).
This study confirms increased prevalence of atherosclerosis in RA and provides
data to support the hypothesis that patients have a high-risk plaque phenotype.
PMID- 28400574
TI - Maternal lipids and leptin concentrations are associated with large-for
gestational-age births: a prospective cohort study.
AB - The change in maternal lipid, leptin and adiponectin concentrations during
pregnancy and infant birth weight (BW) is still poorly characterized. Thus, the
aim of the study was to evaluate the association of maternal lipids, leptin and
adiponectin throughout pregnancy with large-for-gestational-age (LGA) births and
BW z-score. A prospective cohort of 199 mothers was followed during pregnancy in
Rio de Janeiro, Brazil. The statistical analyses comprised multiple logistic and
linear regression. Women delivered 36 LGA and 11 small-for-gestational-age
newborns. HDL-c rate of change throughout pregnancy was negatively associated
with BW z-score (beta = -1.99; p = 0.003) and the delivery of a LGA newborn (OR =
0.02; p = 0.043). Pregnancy baseline concentration of log leptin was positively
associated (OR = 3.92; p = 0.025) with LGA births. LDL-c rate of change
throughout pregnancy was positively associated with BW z-score (beta = 0.31; p =
0.004). Log triglycerides and log adiponectin were not significantly associated
with BW z-score or LGA birth. In conclusion, a higher log leptin pregnancy
baseline concentration and a lower HDL-c rate of change during pregnancy were
associated with higher odds of having a LGA newborn. These maternal biomarkers
are important to foetal growth and could be used in prenatal care as an
additional strategy to screen women at risk of inadequate BW.
PMID- 28400575
TI - Heterologous expression of diverse propionyl-CoA carboxylases affects polyketide
production in Escherichia coli.
PMID- 28400576
TI - A Sputtered Silicon Oxide Electrolyte for High-Performance Thin-Film Transistors.
AB - Low operating voltages have been long desired for thin-film transistors (TFTs).
However, it is still challenging to realise 1-V operation by using conventional
dielectrics due to their low gate capacitances and low breakdown voltages.
Recently, electric double layers (EDLs) have been regarded as a promising
candidate for low-power electronics due to their high capacitance. In this work,
we present the first sputtered SiO2 solid-state electrolyte. In order to
demonstrate EDL behaviour, a sputtered 200 nm-thick SiO2 electrolyte was
incorporated into InGaZnO TFTs as the gate dielectric. The devices exhibited an
operating voltage of 1 V, a threshold voltage of 0.06 V, a subthreshold swing of
83 mV dec-1 and an on/off ratio higher than 105. The specific capacitance was
0.45 uF cm-2 at 20 Hz, which is around 26 times higher than the value obtained
from thermally oxidised SiO2 films with the same thickness. Analysis of the
microstructure and mass density of the sputtered SiO2 films under different
deposition conditions indicates that such high capacitance might be attributed to
mobile protons donated by atmospheric water. The InGaZnO TFTs with the optimised
SiO2 electrolyte also showed good air stability. This work provides a new pathway
to the realisation of high-yield low-power electronics.
PMID- 28400577
TI - Fish oil, lard and soybean oil differentially shape gut microbiota of middle-aged
rats.
AB - High-fat diets have been associated with overweight/obesity and increased
mortality in middle-aged populations. However, it is still unclear how gut
microbiota in middle-aged populations responds to dietary fats at a normal dose.
In this study, we explored gut microbiota structure in middle-aged rats (aged 12
months) after feeding 4% (w/w) soybean oil, lard or fish oil for 3 months,
respectively. The results showed that the gut microbiota structure in the fish
oil group was substantially different from those of the soybean oil and lard
groups in both in vitro and in vivo studies. The relative abundances of phylum
Proteobacteria and genus Desulfovibrio in the caecal and colonic contents were
the highest in the fish oil group (p < 0.05). The mRNA levels of biomarkers for
inflammation in the colon, including IL-1beta, IL-6, IL-17, IL-18 and TNF-alpha,
were also the highest in the fish oil group (p < 0.05). Meanwhile, the fish oil
group had the highest microbial DNA abundance of a predicted lipid metabolism.
Our results gave a new insight into the potentially negative impact of fish oil
diet on health of middle-aged populations by changing gut microbiota and inducing
inflammation as compared to soybean oil and lard diets.
PMID- 28400579
TI - Water-carbon dioxide solid phase equilibria at pressures above 4 GPa.
AB - A solid phase in the mixed water-carbon dioxide system, previously identified as
carbonic acid, was observed in the high-pressure diamond-anvil cell. The pressure
temperature paths of both its melting and peritectic curves were measured,
beginning at 4.4 GPa and 165 degrees C (where it exists in a quadruple
equilibrium, together with an aqueous fluid and the ices H2O(VII) and CO2(I)) and
proceeding to higher pressures and temperatures. Single-crystal X-ray diffraction
revealed a triclinic crystal with unit cell parameters (at 6.5 GPa and 20
degrees C) of a = 5.88 A, b = 6.59 A, c = 6.99 A, alpha = 88.7 degrees , beta =
79.7 degrees , and gamma = 67.7 degrees . Raman spectra exhibit a major line at
~1080 cm-1 and lattice modes below 300 cm-1.
PMID- 28400578
TI - Elevated levels of Wnt signaling disrupt thymus morphogenesis and function.
AB - All vertebrates possess a thymus, whose epithelial microenvironment is essential
for T cell development and maturation. Despite the importance of the thymus for
cellular immune defense, many questions surrounding its morphogenesis remain
unanswered. Here, we demonstrate that, in contrast to the situation in many other
epithelial cell types, differentiation of thymic epithelial cells (TECs) proceeds
normally in the absence of canonical Wnt signaling and the classical adhesion
molecule E-cadherin. By contrast, TEC-intrinsic activation of beta-catenin
dependent Wnt signaling blocks the morphogenesis of the thymus, and
overexpression of a secreted Wnt ligand by TECs dominantly modifies the
morphogenesis not only of the thymus, but also of the parathyroid and thyroid.
These observations indicate that Wnt signaling activity in the thymus needs to be
precisely controlled to support normal TEC differentiation, and suggest possible
mechanisms underlying anatomical variations of the thymus, parathyroid and
thyroid in humans.
PMID- 28400580
TI - Responses of denitrifying bacterial communities to short-term waterlogging of
soils.
AB - Agricultural soil is often subjected to waterlogging after heavy rainfalls,
resulting in sharp and explosive increases in the emission of nitrous oxide
(N2O), an important greenhouse gas primarily released from agricultural soil
ecosystems. Previous studies on waterlogged soil examined the abundance of
denitrifiers but not the composition of denitrifier communities in soil. Also,
the PCR primers used in those studies could only detect partial groups of
denitrifiers. Here, we performed pyrosequencing analyses with the aid of recently
developed PCR primers exhibiting high coverage for three denitrification genes,
nirK, nirS, and nosZ to examine the effect of short-term waterlogging on
denitrifier communities in soil. We found that microbial communities harboring
denitrification genes in the top 5 cm of soil distributed according to soil
depth, water-soluble carbon, and nitrate nitrogen. Short-term waterlogging
scarcely affected abundance, richness, or the alpha-diversities of microbial
communities harboring nirK, nirS, and nosZ genes, but significantly affected
their composition, particularly in microbial communities at soil depths of 0 to 1
cm. Our results indicated that the composition of denitrifying microbial
communities but not the abundance of denitrifiers in soil was responsive to short
term waterlogging of an agricultural soil ecosystem.
PMID- 28400581
TI - Rational development of Stafib-2: a selective, nanomolar inhibitor of the
transcription factor STAT5b.
AB - The transcription factor STAT5b is a target for tumour therapy. We recently
reported catechol bisphosphate and derivatives such as Stafib-1 as the first
selective inhibitors of the STAT5b SH2 domain. Here, we demonstrate STAT5b
binding of catechol bisphosphate by solid-state nuclear magnetic resonance, and
report on rational optimization of Stafib-1 (Ki = 44 nM) to Stafib-2 (Ki = 9 nM).
The binding site of Stafib-2 was validated using combined isothermal titration
calorimetry (ITC) and protein point mutant analysis, representing the first time
that functional comparison of wild-type versus mutant protein by ITC has been
used to characterize the binding site of a small-molecule ligand of a STAT
protein with amino acid resolution. The prodrug Pomstafib-2 selectively inhibits
tyrosine phosphorylation of STAT5b in human leukaemia cells and induces apoptosis
in a STAT5-dependent manner. We propose Pomstafib-2, which currently represents
the most active, selective inhibitor of STAT5b activation available, as a
chemical tool for addressing the fundamental question of which roles the
different STAT5 proteins play in various cell processes.
PMID- 28400582
TI - Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of
primary biliary cholangitis.
AB - Serum anti-mitochondrial antibody type 2 (AMA-M2) is considered as a pivotal
biomarker for the diagnosis of primary biliary cholangitis (PBC). However,
serological tests have many limitations, including inconvenience, invasiveness,
and infection risks. Thus, a less invasive approach to detect AMA-M2 titer is
desirable. We examined salivary AMA-M2 of potential PBC patients and found that
AMA-M2 could be detected only in saliva of serum AMA-M2-positive PBC patients,
but not in saliva of serum AMA-M2-negative PBC patients, oral lichen planus
patients (OLP) patients, or healthy controls. Furthermore, the concentration of
salivary AMA-M2 was positively correlated with the amount of serum AMA-M2 in
patients. The salivary inflammatory cytokines were increased in the PBC,
consistent with the results of serum test. These findings indicated that saliva
might be a less invasive and cost-effective medium to accurately test for AMA-M2
levels and this is a promising development for the diagnosis and monitoring of
PBC.
PMID- 28400583
TI - Effects of sintering temperature on surface morphology/microstructure, in vitro
degradability, mineralization and osteoblast response to magnesium phosphate as
biomedical material.
AB - Magnesium phosphate (MP) was fabricated using a chemical precipitation method,
and the biological performances of MP sintered at different temperatures as a
biomedical material was investigated. The results indicated that the
densification and crystallinity of MP increased as the sintering temperature
increased. As the sintering temperature increased, the degradability of MP in PBS
decreased, and the mineralization ability in SBF significantly increased. In
addition, the MP sintered at 800 degrees C (MP8) possessed the lowest
degradability and highest mineralization ability. Moreover, the positive response
of MG63 cells to MP significantly increased as the sintering temperature
increased, and MP8 significantly promoted the cell spreading, proliferation,
differentiation and expressions of osteogenic differentiation-related genes.
Faster degradation of MP0 resulted in higher pH environments and ion
concentrations, which led to negative responses to osteoblasts. However, the
appropriate degradation of MP8 resulted in suitable pH environments and ion
concentrations, which led to positive responses to osteoblasts. This study
demonstrated that the sintering temperature substantially affected the surface
morphology/microstructure, degradability and mineralization, and osteoblasts
response to magnesium phosphate.
PMID- 28400584
TI - Effects of root spatial distribution on the elastic-plastic properties of soil
root blocks.
AB - Plant roots significantly influence soil properties, especially in soil beyond
the limited area surrounding the main root stem. Some bias results may be
generated if plastic properties of soil are merely used in evaluating slope
stability without considering the effects of plant roots. In this research,
effects of root spatial distribution on the elastic-plastic characteristics of
soil-root blocks were examined. Triaxial tests and the Duncan-Chang model were
used to analyze the correlation between root spatial characteristics and soil
elastic-plastic properties. Safety factors of vegetated slopes were calculated to
investigate the effect of roots on slope stability. The limit stress of remoulded
soil was 103.52% to 231.61% greater than undisturbed soil in shallow soil layers.
Increased root quantity led to an increased the failure ratio of soil bulk and
the initial tangent modulus increased with root diameter. When calculating the
safety factor of vegetated slopes, soil indexes for soil beyond the small
cylinder surrounding the main stem should be properly considered to avoid safety
factor overestimation.
PMID- 28400585
TI - Juvenile Hormone Epoxide Hydrolase: a Promising Target for Hemipteran Pest
Management.
AB - Juvenile hormone epoxide hydrolase (JHEH) has attracted great interest because of
its critical role in the regulation of juvenile hormone (JH) in insects. In this
study, one JHEH gene from Apolygus lucorum (AlucJHEH) was characterized in terms
of deduced amino acid sequence, phylogeny, homology modeling and docking
simulation. The results reveals a conserved catalytic mechanism of AlucJHEH
toward JH. Our study also demonstrates that the mRNA of AlucJHEH gene was
detectable in head, thorax and abdomen from all life stages. To functionally
characterize the AlucJHEH gene, three fragments of double-stranded RNAs (dsRNAs)
were designed to target different regions of the sequence. Injection of 3rd
nymphs with dsRNA fragments successfully knocked down the target gene expression,
and a significantly decreased survival rate was observed, together with a molting
block, These findings confirm the important regulatory roles of AlucJHEH in A.
lucorum and indicate this gene as a promising target for future hemipterans pest
control.
PMID- 28400586
TI - Effect of surface state hybridization on current-induced spin-orbit torque in
thin topological insulator films.
AB - We investigate the thickness optimization for maximum current-induced spin-orbit
torque (SOT) generated by topological surface states (TSS's) in a bilayer system
comprising of a ferromagnetic layer coupled to a thin topological insulator (TI)
film. We show that by reducing the TI thickness, two competing effects on the SOT
are induced: (i) the torque strength is stronger as the bulk contribution is
decreased; (ii) on the other hand, the torque strength becomes suppressed due to
increasing hybridization of the surface states. The latter is attributed to the
opposite helicities of the coupled TSS's. We theoretically model the interplay of
these two effects and derive the optimal TI thickness to maximize the spin
torque, which is estimated to be about 3-5 nm for typical Bi2Se3 films.
PMID- 28400587
TI - Racetrack memory based on in-plane-field controlled domain-wall pinning.
AB - Magnetic domain wall motion could be the key to the next generation of data
storage devices, shift registers without mechanically moving parts. Various
concepts of such so-called 'racetrack memories' have been developed, but they are
usually plagued by the need for high current densities or complex geometrical
requirements. We introduce a new device concept, based on the interfacial
Dzyaloshinskii-Moriya interaction (DMI), of which the importance in magnetic thin
films was recently discovered. In this device the domain walls are moved solely
by magnetic fields. Unidirectionality is created utilizing the recent observation
that the strength with which a domain wall is pinned at an anisotropy barrier
depends on the direction of the in-plane field due to the chiral nature of DMI.
We demonstrate proof-of-principle experiments to verify that unidirectional
domain-wall motion is achieved and investigate several material stacks for this
novel device including a detailed analysis of device performance for consecutive
pinning and depinning processes.
PMID- 28400588
TI - The effect of social connections on the discovery of multiple hidden food patches
in a bird species.
AB - Social foraging is thought to provide the possibility of information transmission
between individuals, but this advantage has been proved only in a handful of
species and contexts. We investigated how social connections in captive flocks of
house sparrows (Passer domesticus) affected the discovery of (i.e. feeding for
the first time from) two hidden food patches in the presence of informed flock
mates. At the first-discovered and most-exploited food patch social connections
between birds affected the order of discovery and presumably contributed to a
greater exploitation of this patch. However, social connections did not affect
discovery at the second food patch despite its close spatial proximity. Males
discovered the food sources sooner than females, while feeding activity was
negatively related to patch discovery. Age had no effect on the order of
discovery. Birds that first discovered and fed at the food patches were
characterized by higher level of social indifference, i.e. followed others less
frequently than other birds in an independent context. Our findings provide
experimental evidence for the importance of variable social connections during
social foraging in house sparrow flocks, and suggest that social attraction can
contribute differently to the exploitation of different patches when multiple
food sources are present.
PMID- 28400589
TI - Excitation Intensity Dependent Carrier Dynamics of Chalcogen Heteroatoms in
Medium-Bandgap Polymer Solar Cells.
AB - The excitation intensity dependent carrier dynamics of blends with PC[70]BM of
three new medium-band gap conjugated polymers with central chalcogen heteroatoms,
PBDTfDTBX (X = O, T(Sulphur), Se) were studied. The PBDTfDTBX polymers (Poly[4,8
bis(5-(2-butyloctyl)thiophene-2-yl)benzo[1,2-b;4,5-b']dithiophene-alt-4,7-bis(4
(2-ethylhexyl)-2-thienyl)-dithieno[3',2':3,4;2",3":5,6]benzo[1,2-c][1,2,5]
furazan or thiadiazole or selenadiazole]) have symmetrical structures but exhibit
different solar cell performances. In this study, we determined how the
photogenerated charge carrrier dynamics of the PBDTfDTBX:PC[70]BM blends varies
with the heteroatom by performing transient absorption measurements at various
excitation intensities. It was found that the charge carrier dynamics of the
PBDTfDTBX blends with X = T or Se heteroatoms are dependent on the excitation
intensity whereas that of the PBDTfDTBO blend is independent of the intensity.
The photogenerated charge carrier dynamics of the PBDTfDTBO:PCBM, PBDTfDTBT:PCBM,
and PBDTfDTBSe:PCBM blends were all modeled globally and rates were estimated for
different photophysical processes occurring on different time scales.
PMID- 28400590
TI - Diversity and role of cave-dwelling hematophagous insects in pathogen
transmission in the Afrotropical region.
AB - The progressive anthropization of caves for food resources or economic purposes
increases human exposure to pathogens that naturally infect cave-dwelling
animals. The presence of wild or domestic animals in the immediate surroundings
of caves also may contribute to increasing the risk of emergence of such
pathogens. Some zoonotic pathogens are transmitted through direct contact, but
many others require arthropod vectors, such as blood-feeding insects. In Africa,
hematophagous insects often play a key role in the epidemiology of many
pathogens; however, their ecology in cave habitats remains poorly known. During
the last decades, several investigations carried out in Afrotropical caves
suggested the medical and veterinary importance particularly of insect taxa of
the Diptera order. Therefore, the role of some of these insects as vectors of
pathogens that infect cave-dwelling vertebrates has been studied. The present
review summarizes these findings, brings insights into the diversity of cave
dwelling hematophagous Diptera and their involvement in pathogen transmission,
and finally discusses new challenges and future research directions.
PMID- 28400592
TI - Recent emergence of a novel porcine pestivirus: interference with classical swine
fever diagnosis?
PMID- 28400591
TI - Pathogenicity and transmission of a swine influenza A(H6N6) virus.
AB - Subtype H6 influenza A viruses (IAVs) are commonly detected in wild birds and
domestic poultry and can infect humans. In 2010, a H6N6 virus emerged in southern
China, and since then, it has caused sporadic infections among swine. We show
that this virus binds to alpha2,6-linked and alpha2,3-linked sialic acids.
Mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the
virus hemagglutinin (HA) affected its receptor-binding properties. Experiments
showed that the virus has limited transmissibility between ferrets through direct
contact or through inhalation of infectious aerosolized droplets. The internal
genes of the influenza A(H1N1)pdm09 virus, which is prevalent in swine worldwide,
increases the replication efficiency of H6N6 IAV in the lower respiratory tract
of ferrets but not its transmissibility between ferrets. These findings suggest
H6N6 swine IAV (SIV) currently poses a moderate risk to public health, but its
evolution and spread should be closely monitored.
PMID- 28400593
TI - Rickettsial seropositivity in the indigenous community and animal farm workers,
and vector surveillance in Peninsular Malaysia.
AB - Rickettsioses are emerging zoonotic diseases that are often neglected in many
countries in Southeast Asia. Rickettsial agents are transmitted to humans through
exposure to infected arthropods. Limited data are available on the exposure of
indigenous community and animal farm workers to the aetiological agents and
arthropod vectors of rickettsioses in Peninsular Malaysia. Serological analysis
of Rickettsia conorii and Rickettsia felis was performed for 102 individuals from
the indigenous community at six rural villages and 87 workers from eight animal
farms in Peninsular Malaysia in a cross-sectional study. The indigenous community
had significantly higher seropositivity rates for R. conorii (P<0.001) and R.
felis (P<0.001), as compared to blood donors from urban (n=61). Similarly, higher
seropositivity rates for R. conorii (P=0.046) and R. felis (P<0.001) were noted
for animal farm workers, as compared to urban blood donors. On the basis of the
sequence analysis of gltA, ompA and ompB, various spotted fever group rickettsiae
closely related to R. raoultii, R. heilongjiangensis, R. felis-like organisms, R.
tamurae, Rickettsia sp. TCM1, R. felis, Rickettsia sp. LON13 and R. hulinensis
were identified from tick/flea samples in animal farms, indigenous villages and
urban areas. This study describes rickettsial seropositivity of the Malaysian
indigenous community and animal farm workers, and provides molecular evidence
regarding the presence of rickettsial agents in ticks/fleas infesting domestic
animals in Peninsular Malaysia.
PMID- 28400595
TI - Prediction of Bacterial Contamination Outbursts in Water Wells through Sparse
Coding.
AB - Maintaining water quality is critical for any water distribution company. One of
the major concerns in water quality assurance, is bacterial contamination in
water sources. To date, bacteria growth models cannot predict with sufficient
accuracy when a bacteria outburst will occur in a water well. This is partly due
to the natural sparsity of the bacteria count time series, which hinders the
observation of deviations from normal behavior. This precludes the application of
mathematical models nor statistical quality control methods for the detection of
high bacteria counts before contamination occurs. As a result, currently a future
outbreak prediction is a subjective process. This research developed a new cost
effective method that capitalizes on the sparsity of the bacteria count time
series. The presented method first transforms the data into its spectral
representation, where it is no longer sparse. Capitalizing on the spectral
representation the dimensions of the problem are reduced. Machine learning
methods are then applied on the reduced representations for predicting bacteria
outbursts from the bacterial counts history of a well. The results show that
these tools can be implemented by the water quality engineering community to
create objective, more robust, quality control techniques to ensure safer water
distribution.
PMID- 28400594
TI - Histo-blood group antigens as receptors for rotavirus, new understanding on
rotavirus epidemiology and vaccine strategy.
AB - The success of the two rotavirus (RV) vaccines (Rotarix and RotaTeq) in many
countries endorses a live attenuated vaccine approach against RVs. However, the
lower efficacies of both vaccines in many low- and middle-income countries
indicate a need to improve the current RV vaccines. The recent discovery that RVs
recognize histo-blood group antigens (HBGAs) as potential receptors has
significantly advanced our understanding of RV diversity, evolution and
epidemiology, providing important new insights into the performances of current
RV vaccines in different populations and emphasizing a P-type-based vaccine
approach. New understanding of RV diversity and evolution also raises a
fundamental question about the 'Jennerian' approach, which needs to be addressed
for future development of live attenuated RV vaccines. Alternative approaches to
develop safer and more cost-effective subunit vaccines against RVs are also
discussed.
PMID- 28400596
TI - The effect of the teeth bleaching with 35% hydrogen peroxide on the tensile bond
strength of metal brackets.
AB - The objective of this study was to determine the effects of teeth bleaching on
the tensile bond strength of metal brackets bonded with light-curing adhesive
system to the human enamel. 40 recently extracted human permanent molars were
used for the study. The mesial buccal surface of each tooth was used as a control
group and the distal buccal surface was used as an experimental group. Control
group surfaces were not submitted to bleaching, while experimental group surfaces
were bleached with in-office bleaching material containing 35% hydrogen peroxide.
30 days after the bleaching, identical premolar metal brackets were bonded to
each surface using light-curing adhesive. Both groups were submitted to a tension
test, using a universal machine. The tensile bond strength of brackets bonded to
the bleached enamel was 15% lower than that of brackets bonded to the unbleached
enamel. After debonding, more adhesive was left on the bracket base in
experimental group than in the control group. The conclusion of this study was
that bleaching with an in-office bleaching material containing 35% hydrogen
peroxide reduced the tensile bond strength of orthodontic bracket adhesive to the
enamel surface.
PMID- 28400598
TI - Molecular dynamics study of ferroelectric domain nucleation and domain switching
dynamics.
AB - Ferroelectric materials contain domains of ordered electric dipoles, separated by
domain walls, that can undergo polarisation switching under externally applied
electric fields. The domain switching dynamics in ferroelectric materials plays
an essential role in their application to electronic and electro-optic de- vices.
Previous studies suggest that the switching occurs largely through domain wall
motion which is explained from the viewpoint of statistical physics on surface
growth as the behaviour of a pinned elas- tic interface. We perform molecular
dynamics simulations to investigate the domain switching process and
quantitatively estimate the switching speed of anti-parallel 180 degrees domains
in ferroelectric, tetragonal BaTiO3 perfect single crystals at room temperature
using the core-shell model. We observe an unprece- dented, non-linear increase in
the domain switching speed caused by the nucleation of new domains within the
switching domain. We determine the strength of the electric field to evoke
nucleation of new domains and show that the nucleated domains diffuse into nearby
favourable domains when the electric field is removed. Furthermore, we discuss
the prominence of domain nucleations during ferroelectric switching.
PMID- 28400597
TI - Indicators of responsiveness to immune checkpoint inhibitors.
AB - Modulation of the immune system can produce anti-tumor responses in various
cancer types, including melanoma. Recently, immune checkpoint inhibitors (ICI),
in single agent and combination regimens, have produced durable and long-lasting
clinical responses in a subset of metastatic melanoma patients. These monoclonal
antibodies, developed against CTLA-4 and PD-1, block immune-inhibitory receptors
on activated T-cells, amplifying the immune response. However, even when using
anti-CTLA-4 and anti-PD-1 in combination, approximately half of patients exhibit
innate resistance and suffer from disease progression. Currently, it is
impossible to predict therapeutic response. Here, we report the first proteomic
and histone epigenetic analysis of patient metastatic melanoma tumors taken prior
to checkpoint blockade, which revealed biological signatures that can stratify
patients as responders or non-responders. Furthermore, our findings provide
evidence of mesenchymal transition, a known mechanism of immune-escape, in non
responding melanoma tumors. We identified elevated histone H3 lysine (27)
trimethylation (H3K27me3), decreased E-cadherin, and other protein features
indicating a more mesenchymal phenotype in non-responding tumors. Our results
have implications for checkpoint inhibitor therapy as patient specific
responsiveness can be predicted through readily assayable proteins and histone
epigenetic marks, and pathways activated in non-responders have been identified
for therapeutic development to enhance responsiveness.
PMID- 28400599
TI - LPS promotes a monocyte phenotype permissive for human cytomegalovirus immediate
early gene expression upon infection but not reactivation from latency.
AB - Human cytomegalovirus (HCMV) infection of myeloid cells is closely linked with
the differentiation status of the cell. Haematopoietic progenitors and CD14+
monocytes are usually non-permissive for lytic gene expression which can lead to
the establishment of latent infections. In contrast, differentiation to
macrophage or dendritic cell (DC) phenotypes promotes viral reactivation or
renders them permissive for lytic infection. The observation that high doses of
Lipopolysaccharide (LPS) drove rapid monocyte differentiation in mice led us to
investigate the response of human monocytes to HCMV following LPS stimulation in
vitro. Here we report that LPS triggers a monocyte phenotype permissiveness for
lytic infection directly correlating with LPS concentration. In contrast,
addition of LPS directly to latently infected monocytes was not sufficient to
trigger viral reactivation which is likely linked with the failure of the
monocytes to differentiate to a DC phenotype. Interestingly, we observe that this
effect on lytic infection of monocytes is transient, appears to be dependent on
COX-2 activation and does not result in a full productive infection. Thus LPS
stimulated monocytes are partially permissive lytic gene expression but did not
have long term impact on monocyte identity regarding their differentiation and
susceptibility for the full lytic cycle of HCMV.
PMID- 28400600
TI - Synthetic Biology: Building a custom eukaryotic genome de novo.
PMID- 28400601
TI - Gene regulation: The nuclear pore - a scaffold for inducible genes.
PMID- 28400602
TI - First Direct Evidence of Pan-African Orogeny Associated with Gondwana Assembly in
the Cathaysia Block of Southern China.
AB - Metamorphic zircon from a hornblendite in the South China Block (SCB) yield U-Pb
age of 533 +/- 7 Ma and Hf model ages from 900 to 1200 Ma. Geochemical and
isotopic characteristics indicate that primary magma of the hornblendites was
probably derived from an enriched asthenospheric mantle source. This Late
Neoproterozoic-Cambrian (Pan-African) metamorphic event provides the first direct
evidence that the SCB was an integral part of the Gondwana assembly. Combined
with available geological data which show that the SCB has great affinity with
India or Australia, the Pan-African metamorphic event most likely belongs to the
eastern Kuunga orogeny. We propose that the SCB was located at the nexus between
India, Antarctica and Australia along the northern margin of East Gondwana, with
the Cathaysia Block connecting western Australia whereas the Yangtze Block facing
northern India at ca. 533 Ma.
PMID- 28400603
TI - Maternal plasma miRNAs as biomarkers during mid-pregnancy to predict later
spontaneous preterm birth: a pilot study.
AB - More than 10% of babies are born too early resulting in over 15 million preterm
births and more than one million new-born deaths globally. Although women with a
previous spontaneous preterm birth (SPTB) are considered at high risk for
recurrence, the majority occur in women without prior history. Prediction of SPTB
risk allows for improved care and potential for targeting novel and existing
therapeutics to prevent SPTB, which may result in improved outcomes for infant
and mother. In this pilot study, a miRNA array was used to analyse plasma from
healthy women in their first pregnancy at 20 weeks of gestation who then went on
to deliver either at term or experience SPTB at 28-32 weeks. We identified
specific miRNA expression profiles that differentiated between those mothers who
delivered at term or delivered following SPTB. miR302b, miR1253 and a clustering
of miR548 miRNAs were underexpressed in SPTB cases compared to term controls.
Conversely, miR223 was elevated in mothers that later experienced a SPTB. The
circulating miRNAs identified in the present study may therefore be attractive
candidates as non-invasive biomarkers for the early prediction of SPTB. Further
larger studies are now warranted to investigate the potential clinical utility of
these markers.
PMID- 28400604
TI - Body Size Predicts Echolocation Call Peak Frequency Better than Gape Height in
Vespertilionid Bats.
AB - In most vocalizing vertebrates, lighter animals tend to produce acoustic signals
of higher frequency than heavier animals. Two hypotheses propose to explain this
negative relationship in vespertilionid bats: (i) mass-signal frequency allometry
and (ii) emitter-limited (maximum gape) signal directionality. The first
hypothesis, that lighter bats with smaller larynges are constrained to calls with
higher frequencies, is supported at the species level. The second hypothesis
proposes that in open space, small bats use higher frequencies to achieve narrow
sonar beams, as beam directionality increases with both emitter size (maximum
gape) and signal frequency. This hypothesis is supported within a comparative
context but remains untested beyond a few species. We analyzed gape, body mass,
and echolocation data under a phylogenetic comparative framework to test these
hypotheses, and considered forearm length as both a proxy for wing design and an
alternative measure of bat size. Controlling for mass, we found no support for
the directionality hypothesis. Body mass and relative forearm length were
negatively related to open space echolocation call peak frequency, reflecting
species-specific size differences, but also the influence of wing design and
preferred foraging habitat on size-independent species-specific differences in
echolocation call design.
PMID- 28400605
TI - An evaluation of the ecological and environmental security on China's terrestrial
ecosystems.
AB - With rapid economic growth, industrialization, and urbanization, various
ecological and environmental problems occur, which threaten and undermine the
sustainable development and domestic survival of China. On the national scale,
our progress remains in a state of qualitative or semi-quantitative evaluation,
lacking a quantitative evaluation and a spatial visualization of ecological and
environmental security. This study collected 14 indictors of water, land, air,
and biodiversity securities to compile a spatial evaluation of ecological and
environmental security in terrestrial ecosystems of China. With area-weighted
normalization and scaling transformations, the veto aggregation (focusing on the
limit indicator) and balanced aggregation (measuring balanced performance among
different indicators) methods were used to aggregate security evaluation
indicators. Results showed that water, land, air, and biodiversity securities
presented different spatial distributions. A relatively serious ecological and
environmental security crisis was found in China, but presented an obviously
spatial variation of security evaluation scores. Hotspot areas at the danger
level, which are scattered throughout the entirety of the country, were
identified. The spatial diversities and causes of ecological and environmental
problems in different regions were analyzed. Spatial integration of regional
development and proposals for improving the ecological and environmental security
were put forward.
PMID- 28400606
TI - Imaging the dynamics of cardiac fiber orientation in vivo using 3D Ultrasound
Backscatter Tensor Imaging.
AB - The assessment of myocardial fiber disarray is of major interest for the study of
the progression of myocardial disease. However, time-resolved imaging of the
myocardial structure remains unavailable in clinical practice. In this study, we
introduce 3D Backscatter Tensor Imaging (3D-BTI), an entirely novel ultrasound
based imaging technique that can map the myocardial fibers orientation and its
dynamics with a temporal resolution of 10 ms during a single cardiac cycle, non
invasively and in vivo in entire volumes. 3D-BTI is based on ultrafast volumetric
ultrasound acquisitions, which are used to quantify the spatial coherence of
backscattered echoes at each point of the volume. The capability of 3D-BTI to map
the fibers orientation was evaluated in vitro in 5 myocardial samples. The
helicoidal transmural variation of fiber angles was in good agreement with the
one obtained by histological analysis. 3D-BTI was then performed to map the fiber
orientation dynamics in vivo in the beating heart of an open-chest sheep at a
volume rate of 90 volumes/s. Finally, the clinical feasibility of 3D-BTI was
shown on a healthy volunteer. These initial results indicate that 3D-BTI could
become a fully non-invasive technique to assess myocardial disarray at the
bedside of patients.
PMID- 28400607
TI - PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma
cells in a manner that involves NFkappaB.
AB - Phosphotyrosine Interaction Domain containing 1 (PID1; NYGGF4) inhibits growth of
medulloblastoma, glioblastoma and atypical teratoid rhabdoid tumor cell lines.
PID1 tumor mRNA levels are highly correlated with longer survival in
medulloblastoma and glioma patients, suggesting their tumors may have been more
sensitive to therapy. We hypothesized that PID1 sensitizes brain tumors to
therapy. We found that PID1 increased the apoptosis induced by cisplatin and
etoposide in medulloblastoma and glioblastoma cell lines. PID1 siRNA diminished
cisplatin-induced apoptosis, suggesting that PID1 is required for cisplatin
induced apoptosis. Etoposide and cisplatin increased NFkappaB promoter reporter
activity and etoposide induced nuclear translocation of NFkappaB. Etoposide also
increased PID1 promoter reporter activity, PID1 mRNA, and PID1 protein, which
were diminished by NFkappaB inhibitors JSH-23 and Bay117082. However, while
cisplatin increased PID1 mRNA, it decreased PID1 protein. This decrease in PID1
protein was mitigated by the proteasome inhibitor, bortezomib, suggesting that
cisplatin induced proteasome dependent degradation of PID1. These data
demonstrate for the first time that etoposide- and cisplatin-induced apoptosis in
medulloblastoma and glioblastoma cell lines is mediated in part by PID1, involves
NFkappaB, and may be regulated by proteasomal degradation. This suggests that
PID1 may contribute to responsiveness to chemotherapy.
PMID- 28400608
TI - Development of Mixed metal Metal-organic polyhedra networks, colloids, and MOFs
and their Pharmacokinetic applications.
AB - The coordination networking of discrete metal-organic polyhedra (MOPs) involving
different ligands as well as metals is a challenging task due to the features of
limited solubility and chemical stability of these polyhedra. An unusual
approach, ligand-oriented polyhedral networking via click chemistry and further
metal coordination is reported here. An alkyne decorated Cu(II)-MOP self
catalyzes the regioselective click reaction (1,3-dipolar cycloaddition) using
azide-functionalized ligands under unconventional reaction conditions.
Introducing new metal ions, M(II), interlinks the carboxylic groups on the MOP
surfaces creating coordination networks. On the other hand, exposure of the
respective individual ligand components in the presence of Cu(II) promotes an in
situ click reaction along with metal coordination generating a new 3D-framework.
These materials demonstrated a high drug hosting potential exhibiting a
controlled progressive release of anticancer (5-flourouracil) and stimulant
(caffeine) drugs in physiological saline at 37 degrees C. These innovative and
unconventional MOP networks provide a significant conceptual advance in
understanding.
PMID- 28400609
TI - Metabolism: Methyl groups sink into phospholipids and histones.
PMID- 28400611
TI - The moment when translational control had a theory of everything.
PMID- 28400612
TI - Differences in mortality characteristics in neonates with Down's syndrome.
PMID- 28400613
TI - The African-American neonate at risk for extreme hyperbilirubinemia: a better
management strategy is needed.
PMID- 28400614
TI - Tropicalization strengthens consumer pressure on habitat-forming seaweeds.
AB - Ocean warming is driving species poleward, causing a 'tropicalization' of
temperate ecosystems around the world. Increasing abundances of tropical
herbivores on temperate reefs could accelerate declines in habitat-forming
seaweeds with devastating consequences for these important marine ecosystems.
Here we document an expansion of rabbitfish (Siganus fuscescens), a tropical
herbivore, on temperate reefs in Western Australia following a marine heatwave
and demonstrate their impact on local kelp forests (Ecklonia radiata). Before the
heatwave there were no rabbitfish and low rates of kelp herbivory but after the
heatwave rabbitfish were common at most reefs and consumption of kelp was high.
Herbivory increased 30-fold and kelp abundance decreased by 70% at reefs where
rabbitfish had established. In contrast, where rabbitfish were absent, kelp
abundance and herbivory did not change. Video-analysis confirmed that rabbitfish
were the main consumers of kelp, followed by silver drummers (Kyphosus
sydneyanus), a temperate herbivore. These results represent a likely indirect
effect of the heatwave beyond its acute impacts, and they provide evidence that
range-shifting tropical herbivores can contribute to declines in habitat-forming
seaweeds within a few years of their establishment.
PMID- 28400615
TI - The Neuromuscular Origins of Kinematic Variability during Perturbed Walking.
AB - We investigated the neuromuscular contributions to kinematic variability and thus
step to step adjustments in posture and foot placement across a range of walking
speeds in response to optical flow perturbations of different amplitudes using a
custom virtual environment. We found that perturbations significantly increased
step width, decreased step length, and elicited larger trunk sway compared to
normal walking. However, perturbation-induced effects on the corresponding
variabilities of these measurements were much more profound. Consistent with our
hypotheses, we found that: (1) perturbations increased EMG activity of the
gluteus medius and postural control muscles during leg swing, and increased
antagonist leg muscle coactivation during limb loading in early stance, and (2)
changes in the magnitude of step to step adjustments in postural sway and lateral
foot placement positively correlated with those of postural control and gluteus
medius muscle activities, respectively, in response to perturbations. However,
(3) interactions between walking speed and susceptibility to perturbations, when
present, were more complex than anticipated. Our study provides important
mechanistic neuromuscular insight into walking balance control and important
reference values for the emergence of balance impairment.
PMID- 28400610
TI - The development and functions of multiciliated epithelia.
AB - Multiciliated cells are epithelial cells that are in contact with bodily fluids
and are required for the proper function of major organs including the brain, the
respiratory system and the reproductive tracts. Their multiple motile cilia beat
unidirectionally to remove particles of external origin from their surface and/or
drive cells or fluids into the lumen of the organs. Multiciliated cells in the
brain are produced once, almost exclusively during embryonic development, whereas
in respiratory tracts and oviducts they regenerate throughout life. In this
Review, we provide a cell-to-organ overview of multiciliated cells and highlight
recent studies that have greatly increased our understanding of the mechanisms
driving the development and function of these cells in vertebrates. We discuss
cell fate determination and differentiation of multiciliated cells, and provide a
comprehensive account of their locations and functions in mammals.
PMID- 28400616
TI - Granulosa cell endothelin-2 expression is fundamental for ovulatory follicle
rupture.
AB - Ovulation is dependent upon numerous factors mediating follicular growth,
vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2
(EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle
rupture by granulosa cells of periovulatory follicles and induces ovarian
contraction. To determine the role of Edn2 expression, surgical transplant and
novel conditional knockout mice were super-ovulated and analyzed. Conditional
knockout mice utilized a new iCre driven by the Esr2 promoter to selectively
remove Edn2. Follicle rupture and fertility were significantly impaired in the
absence of ovarian Edn2 expression. When ovaries of Edn2KO mice were transplanted
in wild type recipients, significantly more corpora lutea containing un-ovulated
oocytes were present after hormonal stimulation (1.0 vs. 5.4, p = 0.010).
Following selective ablation of Edn2 in granulosa cells, Esr2-Edn2KO dams had
reduced oocytes ovulated (3.8 vs. 16.4 oocytes/ovary) and smaller litters (4.29
+/- l.02 vs. 8.50 pups/dam). However, the number of pregnancies per pairing was
not different and the reproductive axis remained intact. Esr2-Edn2KO ovaries had
a higher percentage of antral follicles and fewer corpora lutea; follicles
progressed to the antral stage but many were unable to rupture. Conditional loss
of endothelin receptor A in granulosa cells also decreased ovulation but did not
affect fecundity. These data demonstrate that EDN2-induced intraovarian
contraction is a critical trigger of normal ovulation and subsequent fecundity.
PMID- 28400617
TI - NEK2 induces osteoclast differentiation and bone destruction via heparanase in
multiple myeloma.
PMID- 28400618
TI - Donor type, in addition to transplantation in chronic phase and myeloablative
conditioning, influence transplant survival for patients with advanced chronic
myeloid leukemia in the era of tyrosine kinase inhibitors.
PMID- 28400620
TI - Tunneling nanotubes facilitate autophagosome transfer in the leukemic niche.
PMID- 28400622
TI - Viral hepatitis: The bumpy road to animal models for HBV infection.
PMID- 28400619
TI - Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53
dependent and -independent pathways.
AB - Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified
by the recent finding that lncRNA maternally expressed gene 3 (MEG3) inhibits
tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most
common malignant myeloid disorder in adults, and TP53 mutations or loss are
frequently detected in patients with therapy-related AML or AML with complex
karyotype. Here, we reveal that MEG3 is significantly downregulated in AML and
suppresses leukemogenesis not only in a p53-dependent, but also a p53-independent
manner. In addition, MEG3 is proven to be transcriptionally activated by Wilms'
tumor 1 (WT1), dysregulation of which by epigenetic silencing or mutations is
causally involved in AML. Therefore MEG3 is identified as a novel target of the
WT1 molecule. Ten-eleven translocation-2 (TET2) mutations frequently occur in AML
and significantly promote leukemogenesis of this disorder. In our study, TET2,
acting as a cofactor of WT1, increases MEG3 expression. Taken together, our work
demonstrates that TET2 dysregulated WT1-MEG3 axis significantly promotes AML
leukemogenesis, paving a new avenue for diagnosis and treatment of AML patients.
PMID- 28400621
TI - Biochemistry of malaria parasite infected red blood cells by X-ray microscopy.
AB - Red blood cells infected by the malaria parasite Plasmodium falciparum are
correlatively imaged by tomography using soft X-rays as well as by scanning hard
nano-X-ray beam to obtain fluorescence maps of various elements such as S and Fe.
In this way one can deduce the amount of Fe bound either in hemoglobin or in
hemozoin crystals in the digestive vacuole of the malaria parasite as well as
determine the hemoglobin concentrations in the cytosols of the red blood cell and
of the parasite. Fluorescence map of K shows that in the parasite's schizont
stage the K concentration in the red blood cell cytosol is diminished by a factor
of seven relative to a pristine red blood cell but the total amount of K in the
infected red blood cell is the same as in the pristine red blood cell.
PMID- 28400623
TI - IBD: Risk stratification in children with Crohn's disease.
PMID- 28400624
TI - Liver: BMI, diabetes and liver disease risk in adolescents.
PMID- 28400625
TI - IBD: Oncostatin M promotes inflammation in IBD.
PMID- 28400626
TI - Diarrhoea: Low-cost rotavirus vaccine shows efficacy in Niger.
PMID- 28400629
TI - Biostatistics Series Module 8: Assessing Risk.
AB - In observational studies, as well as in interventional ones, it is frequently
necessary to estimate risk that is the association between an observed outcome or
event and exposure to one or more factors that may be contributing to the event.
Understanding incidence and prevalence are the starting point in any discussion
of risk assessment. Incidence rate uses person-time as the denominator rather
than a simple count. Ideally, rates and ratios estimated from samples should be
presented with their corresponding 95% confidence intervals (CIs). To assess the
importance of an individual risk factor, it is necessary to compare the risk of
the outcome in the exposed group with that in the nonexposed group. A comparison
between risks in different groups can be made by examining either their ratio or
the difference between them. The 2 * 2 contingency table comes in handy in the
calculation of ratios. Odds ratio (OR) is the ratio of the odds of an event in
the exposed group, to the odds of the same event in the nonexposed group. It can
range from zero to infinity. When the odds of an outcome in the two groups are
identical, then the OR equals one. OR >1 indicates exposure increases risk while
OR <1 indicates that exposure is protecting against risk. The OR should be
presented with its 95% CI to enable more meaningful interpretation - if this
interval includes 1, then even a relatively large OR will not carry much weight.
The relative risk (RR) denotes the ratio of risk (probability) of event in
exposed group to risk of same event in the nonexposed group. Its interpretation
is similar (but not identical) to the OR. If the event in question is relatively
uncommon, values of OR and RR tend to be similar. Absolute risk reduction (ARR)
is a measure of the effectiveness of an intervention with respect to a
dichotomous event. It is calculated as proportion experiencing the event in
control group minus the proportion experiencing the event in treated group. It is
often used to denote the benefit to the individual. The reciprocal of ARR is the
number needed to treat (NNT), and it denotes the number of subjects who would
need to be treated to obtain one more success than that obtained with a control
treatment. Alternatively, this could also denote the number that would need to be
treated to prevent one additional adverse outcome as compared to control
treatment. Extended to toxicity, the NNT becomes a measure of harm and is then
known as the number needed to harm (NNH). NNT and NNH are important concepts from
the policy makers perspective and ideally should be calculated in all trials of
therapeutic or prophylactic intervention.
PMID- 28400627
TI - Molecular subtypes in cancers of the gastrointestinal tract.
AB - Malignancies of the gastrointestinal tract are among the most common human
cancers. The distinct tissues of origin give rise to a diverse set of diseases,
such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each
associating with specific clinical features. Genomic and transcriptomic analyses
have further defined the heterogeneity that occurs within these cancers by
identifying so-called molecular subtypes. These subtypes are characterized by
specific genetic aberrations and expression signatures that suggest important
biological differences. Although at first sight this subdivision of organ
specific cancers might increase the complexity of classification, closer analysis
suggests that the subtypes detected in the various malignancies are recurring.
For example, nearly all gastrointestinal cancers appear to present with subtypes
that are either characterized by a mesenchymal gene expression signatures,
extensive immune infiltration or metabolic dysregulation. Additionally, in each
of the gastrointestinal malignancies, a 'canonical' subtype is recognized that
retains characteristic features of the epithelial tissue of origin. These common
themes can enhance our collective understanding of these malignancies, and could
perhaps be therapeutically exploited. In this Review, the identification of
subtypes in the various gastrointestinal cancer types are discussed along with
how they could be incorporated into clinical practice.
PMID- 28400630
TI - Methodology Series Module 8: Designing Questionnaires and Clinical Record Forms.
AB - As researchers, we often collect data on a clinical record form or a
questionnaire. It is an important part of study design. If the questionnaire is
not well designed, the data collected will not be useful. In this section of the
module, we have discussed some practical aspects of designing a questionnaire. It
is useful to make a list of all the variables that will be assessed in the study
before preparing the questionnaire. The researcher should review all the existing
questionnaires. It may be efficient to use an existing standardized questionnaire
or scale. Many of these scales are freely available and may be used with an
appropriate reference. However, some may be under copyright protection and
permissions may be required to use the same questionnaire. While designing their
own questionnaire, researchers may use open- or close-ended questions. It is
important to design the responses appropriately as the format of responses will
influence the analysis. Sometimes, one can collect the same information in
multiple ways - continuous or categorical response. Besides these, the researcher
can also use visual analog scales or Likert's scale in the questionnaire. Some
practical take-home points are: (1) Use specific language while framing the
questions; (2) write detailed instructions in the questionnaire; (3) use mutually
exclusive response categories; (4) use skip patterns; (5) avoid double-barreled
questions; and (6) anchor the time period if required.
PMID- 28400628
TI - Evidence and Suggested Therapeutic Approach in Psoriasis of Difficult-to-treat
Areas: Palmoplantar Psoriasis, Nail Psoriasis, Scalp Psoriasis, and
Intertriginous Psoriasis.
AB - Psoriasis is resistant to treatment and it shows frequent relapse; systemic
treatment is often associated with toxicities, and long-term safety data are
lacking for most of the newer drugs like biologics. Moreover, some body areas
such as hands, feet, intertriginous areas, scalp, and nails are even more
resistant. Frequently, systemic treatments are necessary considering the higher
psychological impact on the patient. There is a lack of agreement on the best
therapeutic modalities in the management of psoriasis involving difficult-to
treat locations. At present, there are no Indian guidelines for these conditions.
Available literature has been reviewed extensively on the treatment of psoriasis
involving difficult-to-treat locations; level of evidence has been evaluated as
per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic
suggestions have been developed. Best care has been employed to consider
socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic
suggestion that is appropriate and logical to be used among Indian population and
people of similar ethnic and socioeconomic background.
PMID- 28400631
TI - Cutaneous Lymphomas in India: Prospects and Limitations.
PMID- 28400632
TI - Management Strategies for Mycosis Fungoides in India.
AB - Mycosis fungoides is the most common primary cutaneous T-cell lymphoma. The
approach to diagnosis and further follow-up is outlined. Evidence for
interventions is based classically on a Tumor Node Metastasis Blood TNMB "stage
based" approach. The treatment options in India are limited. The options as per
risk stratification and prognostic index are discussed. Early stages and low-risk
patients can be managed with expectant policy or skin-directed therapies
including topical steroids and phototherapy; intermediate-risk patients can be
opted for interferons or retinoids or low dose methotrexate along with
radiotherapy including total skin electron beam therapy while high-risk patients
are managed most often with single agent or multiagent palliative chemotherapy.
Patients who are intermediate- or high-risk need management by a multispecialty
team at tertiary care centers.
PMID- 28400633
TI - New Targeted Treatments for Cutaneous T-cell Lymphomas.
AB - Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous
diseases that are very difficult to treat at advanced stages. The development of
monoclonal antibodies is a new hope for the treatment of these diseases.
Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for
CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may
frequently induce long-term remissions in patients with Sezary syndrome but high
dose treatments lead to severe cytopenia, immune depletion, and opportunistic
infections. This treatment is less efficient in mycosis fungoides (MF).
Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to
monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a
very interesting new treatment for advanced tumor MF, Sezary syndrome, and
primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse
event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti
C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region
leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is
very efficient on aggressive peripheral T-cell lymphomas, particularly adult T
cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor
cells. The main limiting events are related to the concomitant depletion of
regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the
immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer
proofs of concept for the clinical development of IPH4102 to treat patients with
advanced CTCL.
PMID- 28400634
TI - A Literature Revision in Primary Cutaneous B-cell Lymphoma.
AB - The term "Primary Cutaneous B-Cell Lymphoma" (PCBCL) comprehends a variety of
lymphoproliferative disorders characterized by a clonal proliferation of B-cells
primarily involving the skin. The absence of evident extra-cutaneous disease must
be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's
lymphoma (NHL) with secondary cutaneous involvement, which may have a completely
different clinical behavior and prognosis. In this article, we have summarized
the clinico-pathological features of main types of PCBCL and we outline the
guidelines for management based on a review of the available literature.
PMID- 28400635
TI - Oral and Cutaneous Lymphomas other than Mycosis Fungoides and Sezary Syndrome in
a Mexican Cohort: Recategorization and Evaluation of International Geographical
Disparities.
AB - BACKGROUND: Nonmycosis fungoides/Sezary syndrome (non-MF/SS) primary cutaneous
lymphomas (PCL) are currently categorized under the 2005-World Health
Organization/European Organization for Research and Treatment of Cancer (WHO
EORTC) classification for PCL. These differ in behavior from secondary cutaneous
lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral
lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid
neoplasms. AIMS: This study aims to report the first series of non-MF/SS PCL,
SCL, and POL in a Mexican cohort, examine the applicability of current
classification systems and compare our findings with those from foreign cohorts.
MATERIALS AND METHODS: Eighteen non-MF/SS PCL, four SCL, and two POL with
available tissue for morphology and immunophenotypic assessment were reclassified
according to the 2005-WHO/EORTC and 2016-WHO classifications. RESULTS: Non-MF/SS
PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative
disorders predominated, followed by Epstein-Barr virus-induced lymphomas, and
peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell
lymphomas (BCL) were primarily of follicle center cell origin followed by
postgerminal lymphomas of the diffuse large BCL variety. CONCLUSIONS: Most non
MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005
WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically
atypical cases. The relative frequencies in our cohort hold closer similarities
to Asian registries than from those of Europe/USA, supporting the concept of
individual and/or racial susceptibility, and the notion of geographical variances
in the rate of lymphomas. In particular, such disparity may arise from viral
induced lymphomas which might show partial geographical restriction.
PMID- 28400636
TI - A Study of Vitiligo in Type 2 Diabetic Patients.
AB - CONTEXT: Diabetes mellitus is associated with many skin manifestations including
vitiligo. Vitiligo occurs more commonly in Type 1 diabetes mellitus. A few recent
studies have shown its increased occurrence in Type 2 diabetes mellitus. AIMS:
This study aims to study the prevalence of vitiligo in Type 2 diabetic patients
and to compare the prevalence of vitiligo in age- and sex-matched group of
nondiabetic population. SETTINGS AND DESIGN: The present study was a hospital
based cross-sectional study conducted in the Department of Dermatology in a
tertiary care hospital. SUBJECTS AND METHODS: Six hundred consecutive consenting
patients of Type 2 diabetes were included in the study group and age- and sex
matched controls were healthy nondiabetic adult volunteers attending the
Department of Dermatology. Fasting and postprandial blood sugar levels were done.
A complete history, physical examination, and wood's lamp examination to detect
vitiligo were conducted. In all those with vitiligo, the type of vitiligo was
noted. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS software version
20.0. Comparison between the presence of vitiligo in cases and controls was done
using Chi-square test with P = 0.05 for significance. RESULTS: Vitiligo was seen
in 12% of cases and 6% of control group which was statistically significant (P <
0.01). There was no significant difference between cases and controls with
respect to type of vitiligo. CONCLUSIONS: Vitiligo can occur in Type 2 diabetics
as seen in our study and few other recent studies. The exact pathogenesis is not
very clear and needs further consideration.
PMID- 28400637
TI - Comparison of Immunofluorescence and Desmoglein Enzyme-linked Immunosorbent Assay
in the Diagnosis of Pemphigus: A Prospective, Cross-sectional Study in a Tertiary
Care Hospital.
AB - BACKGROUND: Pemphigus is an acquired immunobullous disorder in which antibodies
are directed against epidermal cadherins. Despite the commercial availability and
less cost of enzyme-linked immunosorbent assays (ELISAs) to detect antidesmoglein
1 (Dsg1) and anti-Dsg3, immunofluorescence is still widely used for confirmation
of diagnosis. AIMS: (1) To compare the usefulness of indirect immunofluorescence
(IIF) and ELISA tests in the diagnosis of pemphigus. (2) To find the clinical
correlation between the tests and severity of the disease. MATERIALS AND METHODS:
Sixty-one patients (27 women and 34 men, age distribution from 20 to 75) were
clinically diagnosed as pemphigus (pemphigus foliaceus - 11, pemphigus vulgaris -
50) and were recruited for the study. IIF and Dsg ELISA were performed and the
findings were compared with each other and with the pemphigus area activity
score. Data were entered in SPSS and were analyzed using Kruskal-Wallis test.
RESULTS: There was a moderate positive correlation between the cutaneous score
and Dsg1 titer, and mucosal score and Dsg3 titer. The titer of IIF showed
statistically significant positive correlation with the cutaneous score but not
the mucosal score. Dsg ELISA showed higher sensitivity (90.2%) than IIF (75.4%)
in the diagnosis of pemphigus. CONCLUSIONS: Dsg ELISA is a more sensitive method
than IIF and shows more correlation with the disease severity.
PMID- 28400638
TI - Self-medication for Acne among Undergraduate Medical Students.
AB - AIMS: This study aims to evaluate the knowledge and pattern of self-medication
for acne among undergraduate medical students at a tertiary care teaching
hospital. MATERIALS AND METHODS: This cross-sectional study was conducted in II
MBBS (Group A), III MBBS Part I (Group B), and III MBBS Part II (Group C)
students. Prevalidated questionnaire about knowledge, attitude, and practice of
self-medication were administered to participants. Data were analyzed using one
way analysis of variance and Chi-square test. RESULTS: Out of 582 students who
responded to questionnaire, 518 suffered from acne. Self-medication practice was
observed in 59.2% students. Significantly higher number of female students
practiced self-medication (P < 0.0001). Most common source of information was
seniors/friends/family members (34.2%). The mildness of illness (42.3%) was the
most common reason of self-medication. A total mean score of knowledge was
significantly higher in Group C as compared to Group A (P < 0.001) and Group B (P
< 0.05). Allopathic medication was preferred by 69.8% students. Seventy-five
percentage students read leaflet/package insert/label instruction and expiry date
of the medicines. CONCLUSIONS: The participating students lack the knowledge
about self-medication for acne. Adequate knowledge and awareness about the
appropriate use of medication will reduce the practice of self-medication and
improve rational prescribing.
PMID- 28400639
TI - Association of Dermatoses with Duration and Quantum of Alcohol Intake: A
Comparative Cross-sectional Study.
AB - BACKGROUND: Chronic alcohol intake impacts skin directly, through organ
dysfunction or by modifying preexisting dermatoses. However, dermatoses
afflicting chronic alcoholics figure in a few studies only. AIM: This study aims
to correlate the spectrum of dermatoses in chronic alcoholics with the
quantum/duration of alcohol intake and raised liver transaminases. MATERIALS AND
METHODS: Adult males, totaling 196, ascertained to fulfill the Royal College of
Psychiatry criteria for chronic alcoholism by the de-addiction center and
referred for dermatological consult were enrolled as cases, and similar number of
age-/sex-matched teetotallers, as controls. Data emanating from detailed history,
clinical examination, and routine liver functions tests were summarized and
subsequently analyzed, including statistically using the Chi-square, independent
"t" and Spearman's rank correlation tests, and compared with data from previous
studies. RESULTS: Majority (104) drank 41-50 units of alcohol/week since 3-40
(mean: 20.01 +/- 9.322) years. Generalized pruritus (odds ratio [OR]: 31.15, P <
0.001), xerosis (OR: 3.62, P = 0.008), and seborrheic dermatitis (OR: 12.26, P <
0.001) were significantly more common in cases than controls. Infections (73;
37.2%), eczemas (45; 22.9%), and generalized hyperpigmentation (28; 14.2%) were
the major presenting complaints. Spider nevi, gynecomastia, and pellagroid
dermatitis were present in 34 (17.3%), 19 (9.7%), and 8 (4.1%) respectively
exclusively in cases only. Commonly seen systemic abnormalities were an alcoholic
liver disease (45; 22.9%), diabetes mellitus (23; 11.7%), and peripheral
neuropathy (19; 9.7%). CONCLUSION: Knowledge of cutaneous manifestations of
chronic alcoholism could prompt in-depth history taking of alcohol intake, lead
to specialist referral and thereby enable timely de-addiction, hopefully before
serious adversities in the chronic alcoholics.
PMID- 28400640
TI - A Pilot Study Evaluating Therapeutic Response of Different Dosage of Oral
Glucocorticoid in Two Children with Familial Glucocorticoid Deficiency Presenting
with Diffuse Mucocutaneous Hyperpigmentation.
AB - INTRODUCTION: Familial glucocorticoid deficiency (FGD) is a rare autosomal
recessive potentially life-threatening condition, characterized by glucocorticoid
deficiency, preserved aldosterone/renin secretion, and secondary rise in plasma
adrenocorticotropic hormone level. This occurs due to either mutation in
adrenocorticotropic receptor (25%, FGD Type-1) or in the MC2 receptor accessory
protein (15%-20%). However, in about 50% patients, no identifiable mutations have
been identified. Clinically, it manifests with weakness, fatigue, weight loss,
anorexia, nausea, vomiting, diarrhea, abdominal pain, hypoglycemia, and
hypothermia. Progressive mucocutaneous pigmentation is a conspicuous
presentation. Repeated hypoglycemia may result in seizure, persistent
neurological, severe mental disability, and even sudden death. Standard therapy
is oral glucocorticoids (10-15 mg/m2). PATIENTS AND RESULTS: Two familial cases
of FGD were put on progressively increasing doses of oral glucocorticoids (10 mg,
15 mg, and 20 mg/m2/day, each for 6 weeks) to achieve the best response without
any adverse effects. One patient had excellent improvement with 15 mg/m2/day, and
another required 20 mg/m2/day. The latter patient had excellent overall
improvement with only moderate improvement in pigmentation. CONCLUSION:
Glucocorticoids replacement with optimum dose is necessary in FGD to promote
physical and neurological growth and to prevent adrenal crises, hypotension,
hypoglycemia, and sudden death. Higher dose than mentioned in literature (15
mg/m2/day) may be required in selected cases. Mucocutaneous pigmentation may
require even higher dose than we used. More studies are required.
PMID- 28400641
TI - Secukinumab - First in Class Interleukin-17A Inhibitor for the Treatment of
Psoriasis.
AB - Psoriasis is a complex inflammatory disease that occurs in genetically
susceptible individuals and presents with the development of erythematous scaly
plaques on the skin. Interleukins (ILs) in the Th17 pathway play a pivotal role
in the pathogenesis of psoriasis and have thus become targets for recent biologic
drug development. Secukinumab is a human monoclonal IgG1k antibody that has been
developed to target and block the actions of IL-17A. Secukinumab recently
approved for use as first-line systemic therapy in a patient with moderate to
severe psoriasis has been studied first in psoriasis before other diseases. Both
Phase II and III clinical trials have demonstrated the effectiveness of
secukinumab in the treatment of moderate-to-severe plaque psoriasis, and it has
demonstrated superiority to other comparable biologics on the market, including
the tumor necrosis factor inhibitor etanercept. Secukinumab has also shown
superiority to ustekinumab, a relatively recent biologic introduced for the
treatment of psoriasis. Besides demonstrating better efficacy compared to
etanercept and ustekinumab, secukinumab has also demonstrated a greater impact of
the quality of life of patients with a comparable safety profile. Secukinumab
shows great promise in having a tremendous impact on the treatment of plaque
psoriasis based on its ability to produce similar, if not better, clinical
outcomes than other biologic antipsoriasis medications.
PMID- 28400642
TI - CD3+, CD56+, CD4-, CD8-, CD20-, CD30- Peripheral T-Cell Non-Hodgkin's Lymphoma: A
Rare Case Report.
AB - Cutaneous T-cell lymphoma (CTCL) commonly presents as mycosis fungoides or Sezary
syndrome, both having CD4 positivity. A subset of CTCL which lacks CD4 surface
marker is classified as cutaneous gamma and delta-T-cell lymphoma (CGD-TCL).
Because of its rarity and inability to study large number of patients, the impact
of immunophenotype on the clinical outcome of primary CTCL in patients is
limited. We report a case of primary CGD-TCL in a 71-year-old male because of
this rarity and to emphasize its aggressive nature.
PMID- 28400643
TI - Hypopigmented Mycosis Fungoides: Clinical, Histological, and Immunohistochemical
Remission Induced by Narrow-band Ultraviolet B.
AB - Mycosis fungoides (MF) is the most common type of primary cutaneous lymphomas.
Several clinical variants of MF have been described. Purely, hypopigmented
variant of MF (HMF) is rare. Phototherapy, especially photochemotherapy (Psoralen
and ultraviolet), is the most widely used method and is recommended as the first
line treatment for HMF. However, there are no standard guidelines for
phototherapy as the disease is uncommon. We, hereby, report a 30-year-old woman
with HMF in whom clinical, histopathological, and immunohistochemical remission
was achieved following narrow-band ultraviolet B therapy.
PMID- 28400644
TI - Phacomatosis Cesioflammea with Cutis Marmorata-like Lesions and Unusual
Extracutaneous Abnormalities: Is It a Distinct disorder?
AB - A 2-month-old boy was presented with widespread lateralized blue macules (nevus
cesius), an extensive nevus flammeus, and large patches of cutis marmorata
telangiectatica congenita. Moreover, he had macrocephaly, a coarse facial
appearance with depressed nasal bridge, retinal abnormalities, septal defects of
the heart, and obliteration of the left brachiocephalic vein and major veins of
the left arm with pronounced collateralization. The multisystem disorder of this
boy cannot be categorized within the present classification of distinct types of
phacomatosis pigmentovascularis. Although some similar complex cases have
previously been reported, it seems too early to give them a specific name.
Rather, the present case should be included, so far, into the group of
unclassifiable types of phacomatosis pigmentovascularis.
PMID- 28400645
TI - Juvenile Hyaline Fibromatosis: A 10-year Follow-up.
AB - Juvenile hyaline fibromatosis (JHF) is a rare hereditary disease with an
autosomal recessive transmission. JHF is characterized by papulonodular skin
lesions, osteolytic bone lesions, flexural joint contractures, and gingival
hyperplasia and usually diagnosed in infancy or early childhood. JHF is thought
to be a disorder of collagen metabolism and characterized by homogenous amorphous
eosinophilic material and fibrous tissue. We report the case of a 14-year-old
male child with multiple papulonodular skin lesions, progressive flexion
contractures of joints, and severe gingival hyperplasia, with a 10-year follow
up. Although the lesions were totally removed thrice during the last 10 years,
they recurred rigorously.
PMID- 28400646
TI - Role of Clinical Pharmacist in Cosmeto-vigilance of Misuse and Abuse of Topical
Corticosteroids.
PMID- 28400647
TI - Linear Atrophoderma of Moulin over Face: An Exceedingly Rare Entity.
PMID- 28400648
TI - Hemifacial Microsomia and Accessory Auricles in an Adolescent Boy.
PMID- 28400649
TI - Erectile Dysfunction in Behcet's Disease.
PMID- 28400650
TI - A Closer Look at the Term "Tinea Incognito:" A Factual as Well as Grammatical
Inaccuracy.
PMID- 28400651
TI - Untreated Late Latent Syphilis of Both Spouses with Observation of Kassowitz Law:
Adverse Pregnancy Outcomes in the Postpenicillin Era.
PMID- 28400652
TI - A Hairy Plaque over Upper Back of a Young Child.
PMID- 28400653
TI - Clinicopathological Significance among Patients with In vivo Epidermal Nuclear
Staining by Direct Immunofluorescence Study.
AB - CONTEXT: In vivo epidermal nuclear staining (ENS) can be found in patients with
autoimmune connective tissue diseases (CNTDs) and other diseases. AIMS: The aim
of this study was to reveal the underlying diseases and direct immunofluorescence
(DIF) characters of patients with in vivo ENS and association of in vivo ENS with
circulating autoantibodies. SETTINGS AND DESIGN: A retrospective analysis was
conducted involving skin biopsy specimens submitted for DIF study at the
Dermatoimmunology Laboratory at Siriraj Hospital between 2002 and 2012. SUBJECTS
AND METHODS: The findings of DIF study, clinical manifestations, and diagnosis of
patients who had positive ENS were investigated. STATISTICAL ANALYSIS USED: The
SPSS software version 18.0. Descriptive statistics were used to report
demographic data, clinical characteristics, and laboratory investigation results.
Moreover, Chi-squared test or Fisher's exact test were used to compare the
categorical variables. RESULTS: One hundred and thirty-eight out of 3735
submitted specimens (3.7%) showed positive ENS. The most common diagnosis was
CNTD (79%) followed by vasculitis (10.1%). Lupus erythematosus was the most
common diagnosis among CNTD (78%). No association between levels of serum
antinuclear antibodies (ANA) titer and intensity of ENS (P = 0.660). However, we
found that patients with positive in vivo ANA had lower prevalence of systemic
involvement. CONCLUSIONS: Although lupus erythematosus was the most common
diagnosis among patients with in vivo ENS, the presence of ENS does not indicate
any specific diagnosis. However, patients with ENS tend to have less systemic
involvement.
PMID- 28400654
TI - Discoid Lupus and Human Immunodeficiency Virus: A Retrospective Chart Review to
Determine the Prevalence and Progression of Co-occurrence of these Conditions at
a Single Academic Center.
AB - CONTEXT: Discoid lupus erythematosus (DLE) and human immunodeficiency virus (HIV)
are both disorders of the immune system. The pathophysiology of these diseases
varies greatly as DLE is characterized by an overactive immune system that
attacks normal host cells, whereas HIV is characterized by an exogenous attack on
the immune system that depletes it of key cell types. Although the reason is
unknown, co-occurrence of DLE and HIV is rare. AIMS: The goal of this study is to
determine the prevalence of co-occurrence of DLE and HIV and to determine whether
patients with both DLE and HIV share any clinical feature. SUBJECTS AND METHODS:
The medical records of all patients seen within a single academic health center
over a 20-year period were reviewed to determine the prevalence of cutaneous
lupus, HIV, and co-occurrence of these conditions. The charts of patients
diagnosed with both conditions were further reviewed to determine similarities
between them. RESULTS: Of the 10,719 patients diagnosed with HIV and 182 patients
diagnosed with cutaneous lupus, only 2 patients were diagnosed with both
conditions. Both of these patients were diagnosed with DLE several years after
being diagnosed with HIV. They had an undetectable HIV viral load, normal CD4 T
cell counts, and were on antiretroviral therapy when diagnosed with DLE.
CONCLUSION: These results confirm that co-occurrence of DLE and HIV is rare.
Although our study population was small, findings from these patients suggest
that in HIV-positive patients, DLE manifestations occur when their HIV disease
activity is minimal.
PMID- 28400655
TI - Balancing research and clinical practice.
PMID- 28400656
TI - Congenital muscular torticollis: Use of gaze angle and translational deformity in
assessment of facial asymmetry.
AB - BACKGROUND: Assessment of facial asymmetry is challenging in torticollis
deformity. Neck tilt in toroticollis is associated with deviation of horizontal
ocular gaze and translation of neck from the midline. These deviations can be
assessed clinically and can be used as surrogate marker for facial asymmetry.
MATERIALS AND METHODS: Thirty five children with congenital muscular torticollis
(CMT) were classified into three grades of severity based on the new clinical
score. The parameters included in the scoring system included rotational deficit,
side flexion deficit, gaze angle (GA), and translational deformity (TD). Seven
children had Grade I (mild), 18 had Grade II (moderate), and 10 had Grade III
(severe) CMT. There were 21 girls and 14 boys with a mean age of 8.46 years
(range 3-16 years). Twenty two children underwent a bipolar release, and 13 had
unipolar surgery. Facial asymmetry (FA) signs were noted and based on GA and TD;
all children had a deviation from the neutral angles (GA of 90 degrees and 0 mm
translation from the midsterna plumb line were considered neutral angle). The
final outcome was based on the modified Cheng and Tang Score. RESULTS: The mean
GA in Grade I, II, and III improved from 81.71 to 90, 72.77 to 89.16, and 66.60
to 88, respectively (Chi-square P < 0.0001). The TD improved from 15 mm to 0 mm,
25.83 mm to 3.05 mm, and 36.6 mm to 6 mm in Grade I, II, and III, respectively
(Chi-square P < 0.05). The rotational and side flexion deficits also improved
across all grades of severity but were not statistically significant (P < 0.911
and P < 0.04). Twenty four children had an excellent outcome with complete
correction of their GA and TD. Four children with Grade II CMT and seven children
with Grade III who had a residual translation of 5 mm or more and GA less than
neutral horizontal had a good outcome. No child had problems with scar cosmesis
or prominent lateral bands, and there was no recurrence of deformity at a mean
followup of 28 months (range 24-32 months). CONCLUSION: The GA and TD can be used
to assess FA in torticollis management and significant improvement can be
expected even in severe cases.
PMID- 28400657
TI - Transforaminal lumbar interbody fusion versus instrumented posterolateral fusion
in Grade I/II spondylolisthesis.
AB - BACKGROUND: Spondylolisthesis refers to slippage of one vertebra over the other,
which may be caused by a variety of reasons such as degenerative, trauma, and
isthmic. Surgical management forms the mainstay of treatment to prevent further
slip and worsening. However, there is no consensus regarding the best surgical
option to treat these patients. This study compares TLIF and instrumented PLF in
patients with Grade I and II spondylolisthesis and analysis the outcome with
respect to functional outcome, pain, fusion rate, adequacy of medial facetectomy
for decompression, and complications. MATERIALS AND METHODS: Forty patients
operated for spondylolisthesis by instrumented posterolateral or transforaminal
fusion between January 1, 2010, and June 30, 2012 were included in this
retrospective study. They were followed up for 3 years. Twenty one cases were of
instrumented posterolateral fusion (PLF) and 19 cases were of transforaminal
lumbar interbody fusion (TLIF). The patients were asked to fill up the Oswestry
disability index (ODI), Dallas Pain Questionnaire (DPQ), and low back pain rating
scale (LBPRS) preoperatively, at 1-month postoperatively, and at 6, 12, 24, and
36 months postoperatively. Radiological parameters were assessed using
radiographs. RESULTS: No significant differences were found in DPQ, LBPRS, or ODI
scores preoperative, 1-month postoperative, and at 6, 12, 24 and 36 months
followup. No significant difference was found between the two groups in blood
loss. The only significant difference between the two groups was in the operative
time, in which the instrumented PLF group had a mean of 50 min lesser than the
TLIF group (P = 0.02). CONCLUSIONS: TLIF and instrumented PLF are equally
efficacious options in the treatment of Grade I and II spondylolisthesis, except
lytic type.
PMID- 28400658
TI - Complication rate during multilevel lumbar fusion in patients above 60 years.
AB - BACKGROUND: Spine surgery in elderly with comorbidities is reported to have
higher complication rates and increased cost. However, the surgical outcome is
good irrespective of the complications. Hence, it is essential to identify the
factors affecting the complication rates in such patients and the measures to
reduce them. This retrospective observational study determines the perioperative
complications, their incidence and the measures to reduce complications in the
elderly with comorbidities, operated by instrumented multilevel lumbar fusion.
MATERIALS AND METHODS: Patients aged 60 years and above with one or more
comorbidities operated by multilevel instrumented lumbar fusion in our center
between January 2012 and December 2013 were included in the study. Perioperative
complications and their incidence were calculated. Age, number of levels fused,
operative time, blood loss, and complication rates were correlated with the
duration of stay and the incidence of perioperative complications using SPSS
software. Measures to reduce complications are determined by these results and by
review of literature. RESULTS: Fifty two patients were included in the study (28
females and 24 males) with an average age of 69 years (range 60-84 years).
Hypertension was the most common comorbidity followed by diabetes.
Spondylolisthesis was the most common indication. Eleven complications were noted
with an incidence of 21%. Three were systemic complications which required
transfer to Intensive Care Unit. Local complications were incidental durotomy
(three), transient root deficits (two), wound infections (one), and persistent
radicular pain (two). Operative time and blood loss were significantly higher in
patients with complications. CONCLUSION: Complication rates strongly correlate
with the blood loss and operative time. Reducing the operative time and blood
loss by intraoperative tranexamic acid, laminectomy using osteotome, simultaneous
bilateral exposure and instrumentation and reducing the number of interbody
fusions can help in reducing the complications.
PMID- 28400659
TI - Does lumbar paraspinal muscles improve after corrective fusion surgery in
degenerative flat black?
AB - BACKGROUND: Degenerative flat back (DFB) is characterized by sagittal imbalance
resulting from the loss of lumbar lordosis (LL). Extensive degeneration and
weakness of lumbar paraspinal extensor muscle (PSE) are thought to be the main
cause of DFB. This study is to evaluate correlation between preoperative PSE
conditions and angular severity of DFB and to evaluate correlation between
preoperative PSE conditions and degree of improvement of DFB obtained by
corrective surgery. MATERIALS AND METHODS: Forty five patients with DFB who took
magnetic resonance image (MRI) preoperatively and conducted simple radiography
and three-dimensional gait analysis before and 6 months after corrective surgery
were included. To determine the severity of PSE atrophy, the ratio between cross
sectional area of PSE and disc was calculated from L1-L2 to L4-L5 on MRI. To
assess the degree of fat infiltration, the signal intensity of PSE was measured.
Static parameters of spinopelvic segment were measured by simple radiography.
Dynamic parameters of spinopelvic and lower limb joints were obtained by three
dimensional gait analysis. RESULTS: In static parameters, thoracic angle was
correlated with atrophy and fat infiltration of upper PSE. Thoracic angle was
less improved after surgery, as atrophy of upper PSE was more severe. In dynamic
parameters, thoracic angle showed correlation with upper PSE conditions, whereas
lumbar angle had correlation with middle to lower PSE conditions. While thoracic
kyphosis was less improved after surgery, as atrophy of upper PSE was more
severe, LL was less improved, as atrophy and fat infiltration of PSE from L1-L2
to L4-L5 were more severe. CONCLUSIONS: Severity of atrophy or fat infiltration
of PSE showed correlation with degree of angular deformity in patients with DFB
and with less improvement after corrective surgery. Dynamic parameters showed
more prominent correlation with PSE conditions than static parameters and also
showed segmental specificity between PSE and angular deformity.
PMID- 28400660
TI - Anthropometric analysis of the hip joint in South Indian population using
computed tomography.
AB - BACKGROUND: Proximal femur has a significant functional modification on erect
bipedal posture. Various proximal femoral parameters were analyzed in Western
literature. This information was utilized in prosthetic designing. Implants
designed for Western people are used in Indian patients undergoing hip surgeries
such as internal fixation and replacement arthroplasty. MATERIALS AND METHODS:
The study was done among 200 individuals (400 hips) with a normal hip joint after
ethical committee clearance. Computed tomography scanning of proximal femur was
done. Neck-shaft angle (NSA), neck width (NW), head diameter (HD), acetabular
angle (AA) of sharp, horizontal offset (HO), vertical offset (VO), medullary
canal diameter at the level of lesser trochanter (MDLT), and acetabular version
(AV) were measured. These parameters were tabulated and compared with various
populations and statistically analyzed. RESULTS: The mean values were NSA 135
degrees , NW 27 mm, femoral HD (HD) 42.5 mm, AA of sharp 35.5 degrees , HO 37 mm,
VO 46 mm, MDLT20 mm, and AV 18.64 degrees . The values differ when compared with
Western population. This study results differed when compared with other Indian
studies done in Northern and Northeast Indian population. Significant differences
noted in the parameters between sexes and between the sides of the hip joint.
CONCLUSION: This study indicates that there are significant differences in
anthropometric parameters of proximal femur among the South Indian population
compared with Western population. Even within the Indian population, the
anthropometric parameters vary region to region.
PMID- 28400661
TI - Intraoperative measurement of limb lengthening during total hip arthroplasty.
AB - BACKGROUND: Limb length discrepancy (LLD) after total hip arthroplasty (THA) is a
common problem which cannot be completely resolved. Many techniques have been
described in order to minimize postoperative LLD, but most of these techniques
are difficult to apply. Ideal technique must be simple and accurate. The most
simple technique using a suture tied on the skin has well-known limitations, but
its accuracy has not been evaluated before. MATERIALS AND METHODS: Sixty THAs in
sixty patients (mean age 71 years, 1:1 male to female ratio) with hip
osteoarthritis (37 cases in the right, and 23 cases in the left side) were
studied in this prospective study. In all surgeries, the intraoperataive
measurement of limb lengthening was performed using a suture tied on the skin of
the lateral pelvis. The accuracy of this technique and correlation between
intraoperative and postoperative radiological measurements of lengthening were
evaluated. RESULTS: The mean preoperative LLD was -7.5 mm while the mean
postoperative LLD was 1.58 mm. The accuracy of this technique, defined as the
mean difference between the intraoperative and postoperative measurements was 1.8
mm. A strong correlation between these two measurements was noticed (r = 0.86).
CONCLUSION: The accuracy and correlation index of this simple technique were
similar to those of other techniques. The studied technique is quite accurate
when attention is given to certain details, such as the amount of tension applied
on the suture, the position of the tied point on the skin, and the position of
the leg during measurements.
PMID- 28400662
TI - Early anterior cruciate ligament reconstruction can save meniscus without any
complications.
AB - BACKGROUND: Early ACL reconstruction, before retuning to activity eliminates
recurrent episodes of instability and thereby decreases chances of meniscal and
cartilage injury. However, there are no clear and uniform guidelines regarding
the timing of ACL reconstruction or clarity in the definition of early and
delayed reconstruction to reduce the complications after reconstruction in the
ACL injured knee. The purpose of this study was to compare the clinical outcome,
stability, muscle power, and postural control after early and delayed anterior
cruciate ligament (ACL) reconstruction. MATERIALS AND METHODS: Patients who had
ACL reconstruction with a quadruple hamstring tendon with a minimum 2-year
followup were evaluated. Early (within 3 weeks) reconstruction group was 48 knees
and delayed (more than 3 months) group was 43 knees. We compared the two groups
with regard to Lysholm knee score, range of motion (ROM), Lachman test, Tegner
activity scale, associated meniscal or chondral injuries, and anterior laxity. We
also compared muscle strength with an isokinetic dynamometer and postural control
with computed dynamic posturography at the final followup. RESULTS: While 50% of
early and 70% of delayed group had meniscal injuries (P = 0.06), of which were
reparable in 42% of early group and 17% of delayed group (P = 0.04). However,
there was no significant difference in cartilage injury (P = 0.14). At the final
followup, no significant differences were found between two groups for Lysholm
score (P = 0.28), Tegner activity scale (P = 0.27), and ROM. The stabilities
regarding Lachman and pivot-shift tests, and anterior laxity also showed no
significant differences between two groups. The mean extension and flexion
muscles power, and postural control showed no significant inter-group differences
(P > 0.05). CONCLUSIONS: Early ACL reconstruction had excellent clinical results
and stability as good as delayed reconstruction without the problem of knee
motion, muscle power, and postural control. Moreover, early reconstruction showed
the high possibility of meniscal repair. Therefore, early ACL reconstruction
should be recommended.
PMID- 28400663
TI - Tunnel widening prevention with the allo-Achilles tendon graft in anterior
cruciate ligament reconstruction: Surgical tips and short term followup.
AB - BACKGROUND: Tunnel widening (TW) after anterior cruciate ligament (ACL)
reconstruction can be a serious complication, and there is controversy over how
to prevent it. This study aimed to suggest surgical approaches to prevent TW
using an allo-Achilles tendon graft, and then to evaluate TW after these surgical
tips were applied. MATERIALS AND METHODS: Sixty two patients underwent ACL
reconstruction with an allo-Achilles tendon graft. Four surgical approaches were
used: Making a tibial tunnel by bone impaction, intraarticular reamer
application, bone portion application for the femoral tunnel, and an additional
bone plug application for the tibial tunnel. After more than 1-year, followup
radiographs including anteroposterior and lateral views were taken in 29 patients
encompassing thirty knees. The diameter of the tunnels at postoperation day 1
(POD1) and at followup was measured and compared. RESULTS: In 18 knees (60%),
there were no visible femoral tunnel margins on the radiographs at POD1 or
followup. In the other 12 cases, which had visible femoral tunnel margins on
followup radiographs, the mean femoral tunnel diameter was 8.6 mm. In the tibial
tunnel, the mean diameters did not increase on all three levels (proximal,
middle, and distal), and there was no statistically significant difference
between the diameters at POD1 and followup. CONCLUSION: The suggested tips for
surgery involving an allo-Achilles tendon graft can effectively prevent TW after
ACL reconstruction according to this case series. These surgical tips can prevent
TW.
PMID- 28400664
TI - Enhanced recovery protocol and hidden blood loss in patients undergoing total
knee arthroplasty.
AB - BACKGROUND: Perioperative blood loss and postoperative pain following total knee
arthroplasty prevent early mobilisation of patients. The Enhanced Recovery
Protocol (ERP) followed for patients in our institute aims at reducing post
operative pain, blood loss and length of stay. MATERIALS AND METHODS: 50
consecutive patients that underwent ERP following total knee arthroplasty with
another group of 70 patients that underwent the same surgery without ERP were
compared in terms of hidden blood loss and length of hospital stay. Hidden blood
loss was calculated according to previously described method. RESULTS: Reduction
in blood loss was found in both males (305 ml) and females (150 ml) following
ERP. Length of stay reduced by 1.5 days in both genders. Regression analysis
showed a significant correlation between body weight and blood loss in females.
CONCLUSION: Enhanced recovery protocol could be a useful tool to reduce patient
morbidity and reduce length of inpatient stay.
PMID- 28400665
TI - Arthroscopic treatment of displaced tibial eminence fractures using a suspensory
fixation.
AB - BACKGROUND: Avulsion fractures of the tibial intercondylar eminence are fairly
common injuries requiring surgery for the optimal functional outcome. The purpose
of this study was to assess the clinical and radiological outcomes of an
arthroscopic treatment of displaced tibial intercondylar eminence fractures using
a suspensory device. MATERIAL AND METHODS: Five patients with type 2 and 3
displaced tibial intercondylar eminence fractures who received an
arthroscopically assisted fixation using a double button device were enrolled
from 2011 to 2012. Clinical assessment included the patient demographics, cause
of injury, the delay before surgery, time for surgery, time to return to work and
sport, the International Knee Documentation Committee (IKDC) and Lysholm knee
scores. Stability was measured with the KT-2000 arthrometer with a force of 134
N. A side to side difference on the KT-2000 examination superior to 3 mm was
considered as a significant and abnormal increase in the anterior translation.
Radiological examination consisted of anteroposterior and lateral radiographs, as
well as computed tomography (CT) scan of the affected knee. Clinical and
radiological followup was done at 1, 2, 3, 6, and 12 months postoperatively and
at final followup. CT-scan was performed before surgery and at 3 months followup.
RESULTS: The median age of patients was 31 years. Mean followup was 27 +/- 5.1
months. The average delay before surgery was 3 days. At final followup, the mean
IKDC and Lysholm knee scores were, 93.9 and 94.5 respectively. All patients had a
complete functional recovery and were able to return to work and to resume their
sport activities. No secondary surgeries were required to remove hardware. No
complication was noted. Bony union was achieved in all patients. CONCLUSION: The
arthroscopic treatment of displaced tibial intercondylar eminence fractures using
a suspensory system provided a satisfactory clinical and radiological outcome at
a followup of 2 years.
PMID- 28400666
TI - Limited incision carpal tunnel release.
AB - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral entrapment
neuropathy. Limited incision techniques for carpal tunnel release are gaining
popularity. The main advantages of these techniques are less scar load, less
pillar pain, shorter recovery, and return-to-work time. However, the completeness
of release, and risk of neurovascular injury are always a concern. We devised a
method of limited incision release with two mini-incisions and use of nasal
speculum and a probe. We aimed to evaluate the clinical and neurological outcome
of this technique. MATERIALS AND METHODS: Twenty seven cases (9 male and 18
female, age 28-56 years) of isolated CTS cases were enrolled in the study. A
total of 33 hands (six bilateral) underwent limited incision carpal tunnel
release. In this study, two mini-incisions were used and release was done with
the help of nasal speculum. Evaluation preoperatively and in 6 months and at 1
year postoperatively was done, namely, (a) clinical status examination, (b) motor
testing using grip and pinch dynamometer, and (c) neurological outcome measure
using nerve conduction study. RESULTS: All the patients had good clinical and
neurological outcome with no recurrence during followup. The first symptom to get
relieved was night pains, with a mean of 4.5 days (range 2-14 days). Compared to
pain, improvement of sensory symptoms was delayed; the mean duration was 42.8
days (range 30-90 days). Scar tenderness was present only for a mean duration of
9 days (range 7-21 days). The mean duration for patients to resume their daily
activities was12 days (range 7-28 days) and to work was 32 days (range 21-90
days). The hand grip showed mean values of 45.12 +/- 16.16 g/mm2 preoperatively,
62.45 +/- 18.86 g/mm2 at 6 months postoperatively, and 74.87 +/- 20.35 g/mm2 at 1
year postoperatively. The key pinch showed mean values of 11.27 +/- 3.51 g/mm2
preoperatively, 20.181 +/- 3.94 g/mm2 at 6 months postoperatively, and 27.96 +/-
94.42 g/mm2 at 1-year postoperatively. The tip pinch showed mean values of 8.88
+/- 2.39 g/mm2 preoperatively, 15.393 +/- 3.25 g/mm2 at 6 months postoperatively,
and 19.27 +/- 4.81 g/mm2 at 1-year postoperatively. The palmar pinch showed mean
values of 14.42 +/- 2.92 g/mm2 preoperatively, 19.303 +/- 3.62 g/mm2 at 6 months
postoperatively, and 22.97 +/- 4.08 g/mm2 at 1-year postoperatively. CONCLUSION:
Limited incision carpal tunnel release can be considered a feasible alternative
to traditional open release and endoscopic release.
PMID- 28400667
TI - Epidemiology of lower limb musculoskeletal trauma with associated vascular
injuries in a tertiary care institute in India.
AB - BACKGROUND: Vascular trauma associated with bony injuries is an orthopaedic
emergency. Lack of timely intervention can lead to loss of limb or even life.
Inspite of the rising incidence of high speed road traffic accidents in India,
there is paucity of literature regarding the demographic pattern, clinical
morbidity, management strategies and outcome of arterial injuries associated with
lower limb trauma. The aim of this study is to describe the epidemiology and
outcome of lower extremity musculoskeletal trauma with associated vascular
injuries in a tertiary care institute in India. MATERIALS AND METHODS: All
individuals who presented to our tertiary care trauma center from July 2013 to
December 2014 with lower extremity vascular injury associated with lower limb
fractures were identified from a retrospective trauma database for this
descriptive study. For the 17 months, there were 82 lower extremity vascular
trauma cases admitted in our trauma center, of which 50 cases were included in
the study. 32 patients with crush injuries, traumatic amputations, and those with
head injury and blunt trauma to chest or abdomen were excluded from the study.
RESULTS: Out of the 50 cases of lower extremity vascular injury with associated
lower limb fractures, 19 limbs were salvaged, 28 amputated, and three patients
expired. Young males in the age group of 20-39 years were frequently injured.
Motor vehicle accident (MVA) (82%) was found to be the most common cause followed
by pedestrian injury. Popliteal artery (62%) was the most common vessel injured,
followed by femoral artery (28%). The salvageability percentage was much higher
(64%) in the femoral artery injury group when compared to popliteal artery injury
group (25%). There were 32 open fractures, with amputation rates (60%) being
higher and all three cases of death falling in this group. In addition, the limb
salvageability percentage was 43.2% when the patient presented within 12 h of
injury and this decreased to a mere 16.7% when the patient had presented more
than 24 h after injury. CONCLUSION: MVAs are the leading cause of vascular
injuries in India. Road safety measures and prevention programs are the need of
the hour to prevent these kinds of injuries in the future.
PMID- 28400669
TI - Minimally invasive surgical technique for tethered surgical drains.
AB - A feared complication of temporary surgical drain placement is from the technical
error of accidentally suturing the surgical drain into the wound. Postoperative
discovery of a tethered drain can frequently necessitate return to the operating
room if it cannot be successfully removed with nonoperative techniques. Formal
wound exploration increases anesthesia and infection risk as well as cost and is
best avoided if possible. We present a minimally invasive surgical technique that
can avoid the morbidity associated with a full surgical wound exploration to
remove a tethered drain when other nonoperative techniques fail.
PMID- 28400668
TI - Nontuberculous mycobacterial infection of the musculoskeletal system in
immunocompetent hosts.
AB - BACKGROUND: Nontuberculous mycobacteria (NTM) were considered saprophytic
organisms for many years but now are recognized as human pathogens. Although
humans are routinely exposed to NTM, the rate of clinical infection is low. Such
infections usually occur in the elderly and in patients who are
immunocompromised. However, there has been an increasing incidence in recent
years of infections in immunocompetent hosts. NTM infections in immunocompetent
individuals are secondary to direct inoculation either contamination from
surgical procedures or penetrating injuries rather than hematogenous
dissemination. Clinically and on histopathology, musculoskeletal infections
caused by NTM resemble those caused by Mycobacterium tuberculosis but are mostly
resistant to routine antituberculosis medicines. MATERIALS AND METHODS: Six cases
of NTM infection in immunocompetent hosts presenting to the department from 2004
to 2015 were included in study. Of which two cases (one patella and one humerus)
of infection were following an open wound due to trauma while two cases (one hip
and one shoulder) of infection were by inoculation following an intraarticular
injection for arthrogram of the joint, one case was infection following
arthroscopy of knee joint and one case (calcaneum) was infection following local
injection for the treatment of plantar fasciitis. All patients underwent inaging
and tissue diagnosis with samples being sent for culture, staining, and
histopathology. RESULTS: Clinical suspicion of NTM inoculation led to the correct
diagnosis (four cases with culture positive and two cases with histopathological
diagnosis). There treatment protocol for extrapulmonary NTM infection was radical
surgical debridement and medical management based on drug sensitivity testing in
culture positive cases. At a mean follow up of 3 years (range1-9 years) all
patients had total remission and excellent results. CONCLUSIONS: Whenever a case
of chronic granulomatous infection is encountered that does not respond to
standard anti-tuberculous treatment, with a history of open trauma, surgical
intervention, or injection as shown in this study, a possible NTM infection
should be considered and managed appropriately.
PMID- 28400670
TI - Gorham's disease in humerus treated with autogenous vascularized fibular graft.
AB - Gorham's disease is a rare disorder of the bone characterized by progressive
massive osteolysis. The pathophysiology is unknown, and diagnosis is often
difficult. Most cases are often recognized retrospectively. There is no
standardized treatment and management for Gorham's disease. We report a case of
an 18-year-old male presenting with a pathologic fracture in the humerus shaft
diagnosed with Gorham's disease. Patient was treated with autogenous vascularized
fibular graft with wide excision and a 10 years followup after first surgery.
PMID- 28400671
TI - Distraction osteogenesis using combined locking plate and Ilizarov fixator in the
treatment of bone defect: A report of 2 cases.
AB - Distraction osteogenesis and bone transport has been used to reconstruct bone
loss defect by allowing new bone to form in the gap. Plate-guided bone transport
has been successfully described in literature to treat bone loss defect in the
femur, tibia, and mandible. This study reports two cases of fracture of femur
with segmental bone loss treated with locking plate fixation and bone transport
with Ilizarov ring fixator. At the time of docking, when the transport segment is
compressed with bone fragment, the bone fragment is fixed with additional locking
or nonlocking screws through the plate. The bone defect size was 7 cm in case 1
and 8 cm in case 2 and the external fixation indexes were 12.7 days/cm and 14
days/cm. No shortening was present in either of our cases. The average
radiographic consolidation index was 37 days/cm. Both cases achieved infection
free bone segment regeneration and satisfactorily functional outcome. This
technique reduces the duration of external fixation during the consolidation
phase, allows correction of length and alignment and provides earlier
rehabilitation.
PMID- 28400672
TI - Arthroscopic management of popliteal cyst: Comments and concerns.
PMID- 28400673
TI - Author's reply.
PMID- 28400674
TI - Legends of Indian Orthopedics: Dr. Karam Singh Grewal.
PMID- 28400675
TI - Erratum: Management of Gustilo Anderson III B open tibial fractures by primary
fascio-septo-cutaneous local flap and primary fixation: The 'fix and shift'
technique.
AB - [This corrects the article on p. 55 in vol. 51, PMID: 28216752.].
PMID- 28400676
TI - Erratum: Core decompression or quadratus femoris muscle pedicle bone grafting for
nontraumatic osteonecrosis of the femoral head: A randomized control study.
AB - [This corrects the article on p. 629 in vol. 50, PMID: 27904218.].
PMID- 28400677
TI - The Potential Role of Aerobic Exercise-Induced Pentraxin 3 on Obesity-Related
Inflammation and Metabolic Dysregulation.
AB - Obesity is defined as the excess accumulation of intra-abdominal body fat,
resulting in a state of chronic, low-grade proinflammation that can directly
contribute to the development of insulin resistance. Pentraxin 3 (PTX3) is an
acute-phase protein that is expressed by a variety of tissue and cell sources and
provides an anti-inflammatory property to downregulate the production of
proinflammatory cytokines, in particular interleukin-1 beta and tumor necrosis
factor alpha. Although PTX3 may therapeutically aid in altering the
proinflammatory milieu in obese individuals, and despite elevated expression of
PTX3 mRNA observed in adipose tissue, the circulating level of PTX3 is reduced
with obesity. Interestingly, aerobic activity has been demonstrated to elevate
PTX3 levels. Therefore, the purpose of this review is to discuss the therapeutic
potential of PTX3 to positively regulate obesity-related inflammation and discuss
the proposition for utilizing aerobic exercise as a nonpharmacological anti
inflammatory treatment strategy to enhance circulating PTX3 concentrations in
obese individuals.
PMID- 28400679
TI - Erratum to "Establishment of a Consistent L929 Bioassay System for TNF-alpha
Quantitation to Evaluate the Effect of Lipopolysaccharide, Phytomitogens and
Cytodifferentiation Agents on Cytotoxicity of TNF-alpha Secreted by Adherent
Human Mononuclear Cells".
AB - [This corrects the article DOI: 10.1080/09629350123139.].
PMID- 28400678
TI - Key Role of STAT4 Deficiency in the Hematopoietic Compartment in Insulin
Resistance and Adipose Tissue Inflammation.
AB - Visceral adipose tissue (AT) inflammation is linked to the complications of
obesity, including insulin resistance (IR) and type 2 diabetes. Recent data from
our lab showed that germline deficiency in STAT4 reduces inflammation and
improves IR in obese mice. The objective of this study was to determine the
contribution of selective STAT4 deficiency in subsets of hematopoietic cells to
IR and AT inflammation. To determine the contribution of hematopoietic lineage,
we sublethally irradiated Stat4-/-C57Bl6 mice and reconstituted them with bone
marrow cells (BMC) from Stat4+/+C57Bl6 congenic donors. We also established the
contribution of selective STAT4 deficiency in CD4+ or CD8+ T cells using adoptive
transfer in Rag1-/- mice. All mice received a HFD for 15 weeks (n = 7-12
mice/group). BMC that expressed STAT4 induced increases in glucose intolerance
and IR compared to STAT4-deficient cells. Also, AT inflammation was increased and
the numbers of CD8+ cells infiltrating AT were higher in mice with STAT4
expressing BMC. Studies in Rag1-/- mice further confirmed the prominent role of
CD8+ cells expressing STAT4 in insulin resistance and AT and islet inflammation.
Collectively our results show specific and dominant contribution of STAT4 in the
hematopoietic compartment to metabolic health and inflammation in diet-induced
obesity.
PMID- 28400680
TI - Changes in B-type Natriuretic Peptide and Related Hemodynamic Parameters
Following a Fluid Challenge in Critically Ill Patients with Severe Sepsis or
Septic Shock.
AB - CONTEXT: Severe sepsis or septic shock. AIMS: The aim of this study is to examine
the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the
hemodynamic state. SETTINGS AND DESIGN: This observational study was conducted in
an intensivist-led academic, mixed medical-surgical Intensive Care Unit. SUBJECTS
AND METHODS: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic
measurements were recorded at baseline and following a 500 ml fluid challenge in
thirty patients. Independent predictors of the percentage (%) change in stroke
volume (SV) were sought. Next, these independent predictors were assessed for a
relationship with the percentage change in BNP. STATISTICAL ANALYSIS USED:
Multiple linear regressions, Wilcoxon rank-sum test, t-test, and Pearson's
correlation were used. Data analysis was carried out using SAS. The 5%
significance level was used. RESULTS: Using a multiple regression models, the
percentage increase in SV was independently predicted by the percentage increase
in mean arterial pressure, left ventricular end-diastolic volume/dimension
(LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic
Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before
the fluid challenge) was significantly larger in the fluid nonresponders (%SV
increase <15%) vs. the responders (%SV increase >=15%). Finally, the percentage
change in BNP was positively correlated with left ventricular size at end
diastole LVEDd, r = 0.4, P < 0.035). CONCLUSIONS: An increase in BNP soon after a
fluid challenge may have some predictive utility of a large LVEDd, which in turn
can be used to independently predict the SV response to a fluid challenge.
PMID- 28400681
TI - Blood Glucose Variability and Outcomes in Critically Ill Children.
AB - OBJECTIVES: To find the incidence of hyperglycemia (blood glucose [BG] >=150
mg/dl), hypoglycemia (BG <=60 mg/dl), and variability (presence of hypoglycemia
and hyperglycemia) in critically ill children in the 1st week of Intensive Care
Unit (ICU) stay and their association with mortality, length of ICU stay, and
organ dysfunction. MATERIALS AND METHODS: The design was a retrospective
observational cohort study. Consecutive children <=18 years of age admitted from
March 2003 to April 2012 in a combined adult and pediatric closed ICU. Relevant
data were collected from chart review and hospital database. RESULTS: Out of 258
patients included, isolated hyperglycemia was seen in 139 (53.9%) and was
unrelated to mortality and morbidity. Isolated variability in BG was noted in 76
(29.5%) patients and hypoglycemia was seen in 9 (3.5%) patients. BG variability
was independently associated with multiorgan dysfunction syndrome on multivariate
analysis (adjusted odds ratio [OR]: 7.1; 95% confidence interval [CI]: 1.6-31.1).
Those with BG variability had longer ICU stay (11 days vs. 4 days, on log-rank
test, P = 0.001). Insulin use was associated with the occurrence of variability
(adjusted OR: 3.6; 95% CI: 1.8-7.0). CONCLUSION: Glucose disorders were
frequently observed in critically ill children. BG variability was associated
with multiorgan dysfunction and increased ICU stay.
PMID- 28400682
TI - Unplanned Intensive Care Unit Admission following Elective Surgical Adverse
Events: Incidence, Patient Characteristics, Preventability, and Outcome.
AB - CONTEXT: Adverse events (AEs) are a persistent and an important reason for
Intensive Care Unit (ICU) admission. They lead to death, disability at the time
of discharge, unplanned ICU admission (UIA), and prolonged hospital stay. They
impose large financial costs on health-care systems. AIMS: This study aimed to
determine the incidence, patient characteristics, type, preventability, and
outcome of UIA following elective surgical AE. SETTINGS AND DESIGN: This is a
single-center prospective study. METHODS: Analysis of 15,372 elective surgical
procedures was performed. We defined UIA as an ICU admission that was not
anticipated preoperatively but was due to an AE occurring within 5 days after
elective surgery. STATISTICAL ANALYSIS: Descriptive analysis using SPSS software
version 18 was used for statistical analysis. RESULTS: There were 75 UIA (0.48%)
recorded during the 2-year study period. The average age of patients was 54.64 +/
18.02 years. There was no sex predominance, and the majority of our patients had
an American Society of Anesthesiologist classes 1 and 2. Nearly 29% of the UIA
occurred after abdominal surgery and 22% after a trauma surgery. Regarding the
causes of UIA, we observed that 44 UIA (58.7%) were related to surgical AE, 24
(32%) to anesthetic AE, and 7 (9.3%) to postoperative AE caused by care defects.
Twenty-three UIA were judged as potentially preventable (30.7%). UIA was
associated with negative outcomes, including increased use of ICU-specific
interventions and high mortality rate (20%). CONCLUSIONS: Our analysis of UIA is
a quality control exercise that helps identify high-risk patient groups and
patterns of anesthesia or surgical care requiring improvement.
PMID- 28400683
TI - Factors Associated with Reintubation in an Intensive Care Unit: A Prospective
Observational Study.
AB - BACKGROUND AND AIMS: The objective of the study was to determine the incidence of
failed extubations in our Intensive Care Unit (ICU) and identify associated
clinical factors. MATERIALS AND METHODS: A prospective observational study of
mechanically ventilated patients who underwent extubation attempts in our
(predominantly surgical) ICU was undertaken from July 2012 to August 2013. The
primary endpoint was the need for nonelective reintubation within 72 h of
extubation. Clinical data of the reintubated patients were compared with those
who were successfully extubated to identify factors associated with reintubation.
RESULTS: Five hundred and eight extubation attempts were documented, 38 (7.5%) of
which were unsuccessful. On multivariate analysis, the following clinical factors
were found to be associated with an increased risk of failed extubation:
unplanned extubations (adjusted odds ratio [OR] 5.8), the use of noninvasive
ventilation (NIV) postextubation (adjusted OR 3.2), and sepsis (adjusted OR 2.9).
Patient demographic factors, other premorbid and comorbid medical conditions, and
differences of laboratory parameters did not appear to significantly influence
reintubation rates in our study. CONCLUSIONS: Our study has demonstrated a
relatively low reintubation rate, likely due to inclusion of elective
admissions/intubations in our patient population. Unplanned extubations, the use
of NIV postextubation, and sepsis were associated with increased reintubation
risk, reinforcing the need for increased vigilance in this subgroup of patients
after extubation.
PMID- 28400684
TI - Early Prediction of 3-month Survival of Patients in Refractory Cardiogenic Shock
and Cardiac Arrest on Extracorporeal Life Support.
AB - BACKGROUND: Extracorporeal life support (ECLS) holds the promise of significant
improvement of the survival of patient in refractory cardiogenic shock (CS) or
cardiac arrest (CA). Nevertheless, it remains to be shown to which extent these
highly invasive supportive techniques could improve long-term patient's outcome.
METHODS: The outcomes of 82 adult ECLS patients at our institution between
January 2012 and December 2013 were retrospectively analyzed. RESULTS: Patients
were essentially men (64.7%) and are 54 years old. Preexisting ischemic (53.7%)
and dilated cardiomyopathy (14.6%) were frequent. ECLS indications were shared
equally between CA and CS. ECLS-specific adverse effects as hemorrhage (30%) and
infection (50%) were frequent. ECLS was effective for 43 patients (54%) with
recovery for 35 (43%), 5 (6%) heart transplant, and 3 (4%) left ventricular
assist device support. Mortality rate at 30 days was 59.8%, but long-term and 3
month survival rates were similar of 31.7%. Initial plasma lactate levels >5.3
mmol/L and glomerular filtration rate <43 ml/min/1.73 m2 were significantly
associated with 3-month mortality (risk ratio [RR] 2.58 [1.21-5.48]; P = 0.014;
RR 2.10 [1.1-4]; P = 0.024, respectively). Long-term follow-up had shown patients
paucisymptomatic (64% New York Heart Association 1-2) and autonomic (activities
of daily living [ADL] score 6 +/- 1.5). CONCLUSION: In case of refractory CA or
CS, lactates and renal function at ECLS initiation could serve as outcome
predictor for risk stratification and ECLS indication.
PMID- 28400685
TI - Republication: All India Difficult Airway Association 2016 Guidelines for
Tracheal Intubation in the Intensive Care Unit.
AB - Tracheal intubation (TI) is a routine procedure in the Intensive Care Unit (ICU)
and is often lifesaving. In contrast to the controlled conditions in the
operating room, critically ill patients with respiratory failure and shock are
physiologically unstable. These factors, along with under evaluation of the
airway and suboptimal response to preoxygenation, are responsible for a high
incidence of life-threatening complications such as severe hypoxemia and
cardiovascular collapse during TI in the ICU. The All India Difficult Airway
Association (AIDAA) proposes a stepwise plan for safe management of the airway in
critically ill patients. These guidelines have been developed based on available
evidence; Wherever, robust evidence was lacking, recommendations were arrived at
by consensus opinion of airway experts, incorporating the responses to a
questionnaire sent to members of the (AIDAA) and Indian Society of
Anaesthesiologists. Noninvasive positive pressure ventilation for preoxygenation
provides adequate oxygen stores during TI for patients with respiratory
pathology. Nasal insufflation of oxygen at 15 L/min can increase the duration of
apnea before hypoxemia sets in. High flow nasal cannula oxygenation at 60-70
L/min may also increase safety during intubation of critically ill patients.
Stable hemodynamics and gas exchange must be maintained during rapid sequence
induction. It is necessary to implement an intubation protocol during routine
airway management in the ICU. Adherence to a plan for difficult airway management
incorporating the use of intubation aids and airway rescue devices and strategies
is useful.
PMID- 28400687
TI - Using Ultrasonography to Determine Optimal Head-down Tilt Position Angle in
Patients before Catheterization of the Internal Jugular Vein.
AB - CONTEXT: It is believed that 15 degrees -25 degrees head-down tilt position
increases the internal jugular vein cross-sectional area (IJV CSA). The increase
in IJV CSA before puncture reduces the risk of its perforation. This pattern was
not observed in all patients. We assumed that the absence of respiratory-based
IJV excursion is one of the criteria of head-down tilt position effectiveness.
AIMS: The aim of this study is to determine the head-down tilt angle, which
ensures the absence of the respiratory-based IJV excursion. SUBJECTS AND METHODS:
Prospective study included twenty adult patients. The IJVs scanning was carried
out in 1 min after placing the patients in a horizontal position on their back
and in 1 min after placing them in the head-down tilt position at 5 degrees , 10
degrees , 15 degrees , and 20 degrees tilt angles. RESULTS: We found that
collapsibility index of <9% indicating the absence of respiratory-based IJV
excursion was recorded in 25% of patients in the horizontal supine position. In
this case, placing the patients in the Trendelenburg position for IJV
catheterization may not be indicated. In 65% of the patients, the respiratory
based excursion was not observed at 10 degrees head-down tilt position. Only 35%
of the patients required 15 degrees head-down tilt position. CONCLUSIONS: In
clinical settings, the disappearance of respiratory-based vein excursion on the
ultrasound scanner screen can be considered as criteria of the head-down tilt
position effectiveness.
PMID- 28400686
TI - Convergence of Minds: For Better Patient Outcome in Intensive Care Unit
Infections.
AB - BACKGROUND: There is emergence of resistance to the last-line antibiotics such as
carbapenems in Intensive Care Units (ICUs), leaving little effective therapeutic
options. Since there are no more newer antibiotics in the armamentarium in the
near future, it has become imperative that we harness the interdisciplinary
knowledge for the best clinical outcome of the patient. AIMS: The aim of the
conference was to utilize the synergies between the clinical microbiologists and
critical care specialists for better patient care and clinical outcome. MATERIALS
AND METHODS: A combined continuing medical education program (CME) under the
aegis of the Indian Association of Medical Microbiologists - Delhi Chapter and
the Indian Society of Critical Care Medicine, Delhi and national capital region
was organized to share their expertise on the various topics covering
epidemiology, diagnosis, management, and prevention of hospital-acquired
infections in ICUs. RESULTS: It was agreed that synergy between the clinical
microbiologists and critical care medicine is required in understanding the scope
of laboratory tests, investigative pathway testing, hospital epidemiology, and
optimum use of antibiotics. A consensus on the use of rapid diagnostics such as
point-of-care tests, matrix-assisted laser desorption ionization-time of flight
mass spectrometry, and molecular tests for the early diagnosis of infectious
disease was made. It was agreed that stewardship activities along with hospital
infection control practices should be further strengthened for better utilization
of the antibiotics. Through this CME, we identified the barriers and actionables
for appropriate antimicrobial usage in Indian ICUs. CONCLUSIONS: A close
coordination between clinical microbiology and critical care medicine opens up
avenues to improve antimicrobial prescription practices.
PMID- 28400688
TI - Assessing the Performance of a Medical Intensive Care Unit: A 5-year single
center Experience.
AB - Patient care in the Intensive Care Unit (ICU) is complex and expensive, serving
to provide optimal outcome as well as the adequate use of resources. Our
objective was to determine variables associated with admission practices,
processes of care, and clinical outcomes for critically ill patients. Admission
records of a 10-bed ICU were gathered during a 5-year period. Variables such as
average length of stay, bed turnover, bed occupancy rate, and turnover interval
were evaluated. Of the 1719 patients evaluated, 54% were men. Mortality was
highest between 10 pm and 2 am. There was no significant difference in ICU
mortality during different days of the week. We showed that nonoffice hour
admissions were not associated with poorer clinical outcomes, and significant
differences in ICU mortality and ICU length of stay were not seen. Moreover,
hospital mortality rates were not significantly higher for patients admitted to
our ICU on weekends, at nights, or any day of the week.
PMID- 28400689
TI - Toxic Epidermal Necrolysis and Acute Kidney Injury due to Glyphosate Ingestion.
AB - The literature, particularly from India, is scarce on the renal effects of
glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but
also after dermal exposure by inhalation route and on eye exposure. We present a
patient report of glyphosate consumption which resulted in toxic epidermal
necrolysis - the first report after glyphosate consumption and acute kidney
injury.
PMID- 28400690
TI - Transient Distal Renal Tubular Acidosis in Organophosphate Poisoning.
AB - Renal complications due to organophosphate poisoning are very rare. We are
presenting a unique case of transient distal renal tubular acidosis due to
organophosphate poisoning, which to the best of our knowledge is the first of its
kind. An elderly female after deliberate self-harm with ingestion of chlorpyrifos
had multiple ventricular arrhythmias due to hypokalemia secondary to distal renal
tubular acidosis which improved completely after treatment.
PMID- 28400691
TI - Metastatic Endogenous Endophthalmitis: A Rare Presentation with Methicillin
resistant Staphylococcus aureus Prostatic Abscess.
AB - A 62-year-old male with the previous history of uncontrolled diabetes and
hypertension on irregular treatment presented with a history of fever, dysuria,
and urinary retention with progressive painful loss of vision over a period of 2
days. His eye examination showed hypopyon, and he was diagnosed to have rapidly
progressive endogenous endophthalmitis. He was started on vancomycin and
piperacillin-tazobactam empirically. His blood and urine cultures grew
methicillin-resistant Staphylococcus aureus (MRSA). Transesophageal
echocardiography ruled out infective endocarditis. Intravitreal injection of
vancomycin and ceftazidime was given. Vitreous culture also grew MRSA. A workup
for possible source revealed multiple prostatic abscesses on the transrectal
ultrasound. Antibiotic was changed to daptomycin in view of high vancomycin
minimum inhibitory concentration. His vision was improved at the time of
discharge.
PMID- 28400692
TI - Severe Hypertriglyceridemia Causing Pancreatitis in a Child with New-onset Type-I
Diabetes Mellitus Presenting with Diabetic Ketoacidosis.
AB - The triad of pancreatitis, hypertriglyceridemia, and diabetic ketoacidosis and
its treatment has not been extensively discussed in the pediatric literature. We
report a 4-year-old child with severe hypertriglyceridemia, pancreatitis, and
diabetic ketoacidosis. Hypertriglyceridemia and pancreatitis with diabetic
ketoacidosis can be successfully managed with insulin and hydration therapy in
children. Early recognition of this triad is important as insulin requirements,
recovery duration, and prognosis can be altered.
PMID- 28400693
TI - Ludwig's Angina: A Nightmare Worsened by Adverse Drug Reaction to Antibiotics.
AB - A 52-year-old obese gentleman presented to the hospital with complaints of fever
and shortness of breath for 10 days. He was admitted in the ward and treated for
acute exacerbation of asthma. He was shifted to the Intensive Care Unit (ICU) for
persistent fever, neck swelling, airway obstruction and desaturation. Ludwig's
angina was suspected and computed tomography of neck confirmed it. A difficult
airway was anticipated and preceded with surgical tracheostomy. The patient had
hypersensitivity reactions to piperacillin/tazobactam; hence, he was treated with
clindamycin and metronidazole. The patient improved and was discharged after five
days of ICU stay and 12 days of hospitalization. This case summarizes the rare
incidence of Ludwig's angina with antibiotic adverse reactions. If angioneurotic
edema is coincidental with features of Ludwig's angina, it becomes more
challenging. Early identification, securing the airway, and antibiotic
administration are the keystone to better survival.
PMID- 28400694
TI - Sophism in the Management of Acute Aluminum Phosphide Poisoning may Cause Patient
Harm.
PMID- 28400695
TI - Volatile Anesthetic for Management of Super-refractory Status Epilepticus.
PMID- 28400696
TI - Seprafilm(r) Application Method in Laparoscopic Surgery.
AB - BACKGROUND AND OBJECTIVES: Postoperative adhesions occur less often in
laparoscopies than in laparotomies, but the incidence can be reduced further.
Seprafilm, a sodium hyaluronate/carboxymethylcellulose absorbable barrier, was
developed to prevent adhesions after abdominal surgery, and is approved for
postoperative adhesion prevention. However, Seprafilm is seldom used in
laparoscopic surgery because of its tendency to break apart when it is inserted
into the abdominal cavity through a trocar, resulting in a high placement failure
rate. We propose a better method for applying the adhesion barrier Seprafilm in
single- or multiport gynecologic surgery. METHODS: This is a retrospective
analysis of patients who underwent multi- or single-port gynecologic
laparoscopies from December 2014 through January 2016 in Buddhist Tzu Chi General
Hospital, Hualien, 46 patients received Seprafilm (Genzyme Corp., Cambridge, MA,
USA) via the proposed method. A piece of Seprafilm was cut into quarters. To
moisten and soften the Seprafilm, each piece was placed on a wet wrung gauze
until it became naturally curled. Two pieces of the film were rolled up with the
backing paper that came from the package of Seprafilm. Holding the rolled
Seprafilm with a grasper, the surgeon delivered it into the abdomen through a 11
mm trocar. RESULTS: The success rates of Seprafilm insertion and correct
placement were 100% (46/46) and 95.7%, respectively. In 2 single-port (2/26)
laparoscopic surgeries, the placement of the film failed; all placements in the
multiport laparoscopic surgeries were successful (20/20). The average time
required for placement of pieces of Seprafilm per surgery was 4.0 +/- 1.47
minutes among all surgeries; significantly more time was needed in the single
port surgeries (mean, 4.4 +/- 1.59 minutes) than in the multiport surgery (mean,
3.4 +/- 1.13 minutes) (P < .05). CONCLUSIONS: This method of Seprafilm placement
is a simple technique that does not need special equipment and ensures a high
success rate. The placement of the film takes longer in single-port surgeries
than in multiport surgeries.
PMID- 28400697
TI - The Impact of Individual Surgeon Volume on Hysterectomy Costs.
AB - BACKGROUND AND OBJECTIVE: Hysterectomy is one of the most common surgical
procedures women will undergo in their lifetime. Several factors affect surgical
outcomes. It has been suggested that high-volume surgeons favorably affect
outcomes and hospital cost. The objective is to determine the impact of
individual surgeon volume on total hospital costs for hysterectomy. METHODS: This
is a retrospective cohort of women undergoing hysterectomy for benign indications
from 2011 to 2013 at 10 hospitals within the University of Pittsburgh Medical
Center System. Cases that included concomitant procedures were excluded. Costs by
surgeon volume were analyzed by tertile group and with linear regression.
RESULTS: We studied 5,961 hysterectomies performed by 257 surgeons: 41.5%
laparoscopic, 27.9% abdominal, 18.3% vaginal, and 12.3% robotic. Surgeons
performed 1-542 cases (median = 4, IQR = 1-24). Surgeons were separated into
equal tertiles by case volume: low (1-2 cases; median total cost, $4,349.02; 95%
confidence interval [CI] [$3,903.54-$4,845.34]), medium (3-15 cases; median total
cost, $2,807.90; 95% CI [$2,693.71-$2,926.93]) and high (>15 cases, median total
cost $2,935.12, 95% CI [$2,916.31-$2,981.91]). ANOVA analysis showed a
significant decrease (P < .001) in cost from low-to-medium- and low-to-high
volume surgeons. Linear regression showed a significant linear relationship (P <
.001), with a $1.15 cost reduction per case with each additional hysterectomy.
Thus, if a surgeon performed 100 cases, costs were $115 less per case (100 *
$1.15), for a total savings of $11,500.00 (100 * $115). CONCLUSION: Overall, in
our models, costs decreased as surgeon volume increased. Low-volume surgeons had
significantly higher costs than both medium- and high-volume surgeons.
PMID- 28400698
TI - Laparoscopic Rectopexy with Urinary Bladder Xenograft Reinforcement.
AB - BACKGROUND AND OBJECTIVES: Rectal prolapse is often repaired laparoscopically,
frequently with the use of reinforcement material. Both synthetic and
biologically derived materials reduce recurrence rate compared to primary suture
repair. Synthetic mesh introduces potential complications such as mesh erosion,
fibrosis, and infection. Urinary bladder matrix (UBM) represents a biologically
derived material for reinforcement of rectal prolapse repair with the potential
to improve durability without risks of synthetic materials. The objective of the
study is to evaluate the effectiveness, durability, and functional result of
laparoscopic rectopexy using urinary bladder matrix xenograft reinforcement at
three years follow up. METHODS: The 20 cases presented describe rectal prolapse
repair by means of laparoscopic rectopexy with presacral UBM reinforcement.
Patients were followed up for an average of 3 years and assessed with interviews,
physical examination, manometry, and the fecal incontinence severity index
(FISI). RESULTS: Each repair was completed laparoscopically. UBM exhibited
favorable handling characteristics when sutured to the sacrum and the lateral
rectal walls. One patient underwent laparoscopic drainage of a postoperative
abscess; no other complications occurred. In 3 years of follow-up, there have
been no full-thickness recurrences, erosions, reoperations, or long-term
complications. Two patients exhibited a small degree of mucosal prolapse on
follow-up physical examination that did not require surgery. Three-year FISI
scores averaged 8 (range, 0-33 of a possible 61), indicating low fecal
incontinence symptomatology. Follow-up anorectal manometry was performed in 9
patients, showing mixed results. CONCLUSION: Surgeons may safely use laparoscopic
rectopexy with UBM reinforcement for repair of rectal prolapses. In this series,
repairs with UBM grafts have been durable at 3-year follow-up and may be an
alternative to synthetic mesh reinforcement of rectal prolapse repairs. Future
studies may compare the advantages and cost-effectiveness of reinforcement
materials for rectal prolapse repair.
PMID- 28400699
TI - LADD syndrome with glaucoma is caused by a novel gene.
AB - PURPOSE: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant
disorder displaying variable expression of multiple congenital anomalies
including hypoplasia or aplasia of the lacrimal and salivary systems causing
abnormal tearing and dry mouth. Mutations in the FGF10, FGFR2, and FGFR3 genes
were found to cause some cases of LADD syndrome in prior genetic studies. The
goal of this study is to identify the genetic basis of a case of LADD syndrome
with glaucoma and thin central corneal thickness (CCT). METHODS: Whole exome
sequencing was performed, and previously described disease-causing genes (FGF10,
FGFR2, and FGFR3) were first evaluated for mutations. Fifty-eight additional
prioritized candidate genes were identified by searching gene annotations for
features of LADD syndrome. The potential pathogenicity of the identified
mutations was assessed by determining their frequency in large public exome
databases; through sequence analysis using the Blosum62 matrix, PolyPhen2, and
SIFT algorithms; and through homology analyses. A structural analysis of the
effects of the top candidate mutation in tumor protein 63 (TP63) was also
conducted by superimposing the mutation over the solved crystal structure.
RESULTS: No mutations were detected in FGF10, FGFR2, or FGFR3. The LADD syndrome
patient's exome data was searched for mutations in the 58 candidate genes and
only one mutation was detected, an Arg343Trp mutation in the tumor protein 63
(TP63) gene. This TP63 mutation is absent from the gnomAD sequence database.
Analysis of the Arg343Trp mutation with Blosum62, PolyPhen2, and SIFT all suggest
it is pathogenic. This arginine residue is highly conserved in orthologous genes.
Finally, crystal structure analysis showed that the Arg343Trp mutation causes a
significant alteration in the structure of TP63's DNA binding domain.
CONCLUSIONS: We report a patient with no mutations in known LADD syndrome genes
(FGF10, FGFR2, and FGFR3). Our analysis provides strong evidence that the
Arg343Trp mutation in TP63 caused LADD syndrome in our patient and that TP63 is a
fourth gene contributing to this condition. TP63 encodes a transcription factor
involved in the development and differentiation of tissues affected by LADD
syndrome. These data suggest that TP63 is a novel LADD syndrome gene and may also
influence corneal thickness and risk for open-angle glaucoma.
PMID- 28400701
TI - Studies on the exercise physiology of draft horses performed in Japan during the
1950s and 1960s.
AB - Although the total number of horses raised in Japan dramatically decreased after
World War II, because draft horses were still used for farm work in paddy fields
and on farms during the period of the 1950s and 1960s, a performance test for
selecting better draft horses was needed. In order to determine the most suitable
size of draft horses for Japanese farm conditions, the working power of horses
weighing from 185 to 622 kg was evaluated by performing an endurance test,
several kinds of working power tests, and maximum pulling power tests. Oxygen
consumption during draft exercise was measured by the Douglas bag method in order
to evaluate effects of draft workload under the conditions of different types of
work (14- and 18-cm plow depths, cultivator, and tillage), traction methods
(shoulder traction, shoulder-trunk traction, and chest-trunk traction), walking
speeds (40, 60, 80, 100, and 120 m/min), and depths of water (0, 18, 36, and 54
cm) on energy expenditure. The relationship between energy consumption and pulse
rate during exercise was also evaluated. A study of a performance test for draft
horses was conducted to establish a new approach for evaluating draft horse
performance using heart rate as an index. For this study, a beat meter for
measuring heart rate was developed, and experimental protocols were used to
evaluate the relationship between heart rate and workload. Although the research
results obtained from these studies do not have particular relevance in the
current day, these studies are valuable for understanding the history of equine
exercise physiology in Japan.
PMID- 28400700
TI - Serum retinol-binding protein-induced endothelial inflammation is mediated
through the activation of toll-like receptor 4.
AB - PURPOSE: Elevation of serum retinol-binding protein 4 (RBP4) induces inflammation
in primary human retinal microvascular endothelial cells (HRECs) via a retinol
independent mechanism; thus, it may play a causative role in the development and
progression of vascular lesions in diabetic retinopathy (DR). Since HRECs do not
express the classical RBP4 receptor, stimulated by retinoic acid gene 6 (STRA6),
this study focuses on identifying the endothelial cell receptor and signaling
that mediate RBP4-induced inflammation. METHODS: HRECs were treated with a toll
like receptor 4 (TLR4) small molecule inhibitor (Cli95, also known as TAK-242),
TLR4 neutralizing antibody, or mitogen-activated protein kinase (MAPK) inhibitors
before treatment with purified recombinant RBP4. The HREC inflammatory response
was quantified by in vitro leukostasis assays, western blotting, and enzyme
linked immunosorbent assay (ELISA). To understand how the serum binding partner
for RBP4, transthyretin (TTR), may affect RBP4 activity, we also measured RBP4
and TTR levels in serum and retinal lysates from RBP4-Tg and wild-type mice.
RESULTS: TLR4 inhibition significantly reduced RBP4-induced expression of pro
inflammatory proteins and in vitro leukostasis. RBP4 treatment significantly
increased phosphoactivation of p38 and c-Jun N-terminal protein kinase (JNK). The
p38 inhibitor (SB203580) attenuated RBP4-stimulated vascular cell adhesion
molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), monocyte
chemoattractant protein (MCP-1), and interleukin 6 (IL-6) production, while the
JNK inhibitor (SP600125) reduced RBP4-stimulated sICAM-1, endothelial cell
selectin (E-selectin), and MCP-1 production. The MAPK inhibitors only showed
partial (50-70%) suppression of the RBP4-stimulated proinflammatory response.
Moreover, TLR4 inhibition did not decrease RBP4-induced MAPK phosphoactivation,
suggesting that RBP4-mediated MAPK activation is TLR4 independent and occurs
through a secondary unknown receptor. We also found that the RBP4/TTR molar ratio
was exceptionally high in the retina of RBP4-Tg mice, indicating an abundance of
TTR-free RBP4. CONCLUSIONS: RBP4-induced inflammation is largely mediated by
TLR4, and in part, through JNK and p38 MAPK signaling. The high TTR/RBP4 molar
ratio in serum likely protects the endothelium from the proinflammatory effects
of RBP4 in vivo, whereas elevation of serum RBP4 causes a significant increase in
TTR-free RBP4 in retinal tissue. This offers insight into how RBP4-Tg mice can
develop retinal neurodegeneration without coincident retinal microvascular
pathology.
PMID- 28400702
TI - Application of a wearable GPS unit for examining interindividual distances in a
herd of Thoroughbred dams and their foals.
AB - Global positioning system (GPS) units are now lightweight and compact. They have
proven useful for analyzing the behavioral characteristics of horses in pastures.
Because the GPS records data in latitude and longitude, it may be feasible to
calculate the distance between GPS units. The present study aimed to confirm the
applicability of GPS units in behavioral studies on horses. For this, we analyzed
the accuracy of the distances calculated from GPS units using Hubeny's distance
formula and of the monthly changes in interindividual distances obtained from GPS
units worn by Thoroughbred dams and their foals in a pasture until weaning. The
calculated inter-GPS distances were highly accurate. The regression line was
linear, and the squared correlation coefficient (r2) was 0.9998. During the first
month of age, the interindividual dam-dam and foal-foal distances were
significantly greater than the dam-foal distance. During the second month of age,
the dam-foal distance increased once and gradually decreased up to the fifth
month of age. During the sixth month of age, the dam-foal distance was
significantly greater than the foal-foal distance. The GPS distances calculated
using Hubeny's distance formula were useful for analyzing changes in
interindividual distances in a herd of Thoroughbred dams and their foals. Most
likely, calculation of the distance between GPS units worn on equine head collars
is likely to become a very useful tool as an objective index for quantifying
equine behavioral observations.
PMID- 28400703
TI - New methods for isolation of keratolytic bacteria inducing intractable hoof wall
cavity (Gidoh) in a horse; double screening procedures of the horn powder agar
translucency test and horn zymography.
AB - To establish a new system to isolate keratolytic bacteria from the hoof wall
cavity (Gidoh) of a racehorse, we invented the horn powder agar-translucency
(HoPAT) test and horn zymography (HZ). Using routine bacteriological techniques
and these methods, we isolated five strains of keratolytic soil bacteria, which
were then identified by means of 16S ribosomal RNA (rRNA) gene sequencing
analysis. The findings from the study on the horse suggested that Brevibacterium
luteolum played the main role in the local fragility of the hoof, eventually
forming a Gidoh in coordination with four other strains of keratolytic bacteria.
The double screening procedures of the HoPAT test and HZ were useful and easy
techniques for isolating the keratolytic bacteria from the horn lesions.
PMID- 28400704
TI - Effects of dystocia on blood gas parameters, acid-base balance and serum lactate
concentration in heavy draft newborn foals.
AB - Dystocia is often lethal for neonatal foals; however, its clinicopathological
features remain largely unknown. We investigated the effect of dystocia on the
foal blood profile. Venous blood samples were collected from 35 foals (5
Percheron and 30 crossbreds between Percheron, Belgian, and Breton heavy draft
horses) at 0 hr, 1 hr, 12 hr and 1 day after birth. Dystocia was defined as
prolonged labor >30 min with strong fetal traction with or without fetal
displacement. The dystocia group (n=13) showed lower mean values for pH (P<0.01),
bicarbonate (P<0.01), total carbon dioxide (P<0.05), and base excess (P<0.01) and
higher mean values for anion gap (P<0.05) and lactate (P<0.01) immediately after
birth than the normal group (n=22). Remarkably high pCO2 values (>90 mmHg) were
observed in three foals in the dystocia group but in none of the foals in the
normal birth group immediately after birth. These results suggest that dystocia
results in lactic acidosis and may be related to respiratory distress.
PMID- 28400705
TI - High expression of Rab25 contributes to malignant phenotypes and biochemical
recurrence in patients with prostate cancer after radical prostatectomy.
AB - BACKGROUND: Ras-related protein 25 (Rab25) functions either as an oncogene or a
tumor suppressor with a cancer type-dependent manner. We aimed to investigate
clinical significance of Rab25 in prostate cancer (PCa). METHODS: Quantitative
real-time polymerase chain reaction, Western blot and immunohistochemistry were
respectively performed to detect Rab25 mRNA and protein expression in PCa and
adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve
analysis was used to evaluate predictive diagnostic value of Rab25. Associations
of Rab25 expression with various clinicopathological characteristics and
biochemical recurrence-free survival of PCa patients were statistically
evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the
cell migration and invasion activities were evaluated by Transwell assay,
following the transfection of Rab25 small interfering RNA. RESULTS: Ras-related
protein 25 mRNA and protein expression in PCa tissues were both significantly
higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area
under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with
74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly
associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01).
PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence
free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression
analysis identified Rab25 as an independent biomarker for both overall and
biochemical recurrence-free survivals of PCa patients. By exploring its
activities in vitro, Rab25 downregulation was found to inhibit PCa cell
proliferation, migration and invasion. CONCLUSIONS: High expression of Rab25 may
contribute to malignant progression and biochemical recurrence of PCa patients
after radical prostatectomy.
PMID- 28400706
TI - Hypersensitivity reactions due to black henna tattoos and their components: are
the clinical pictures related to the immune pathomechanism?
AB - Hypersensitivity to para-phenylenediamine (PPD) and related compounds induced by
temporary black henna tattoos has become a serious health problem worldwide.
Different patterns of sensitization with various clinical aspects are described
in literature due to PPD associated to henna tattoo and these manifestations are
likely correlated with the immunological and dermatological pathomechanisms
involved. Henna is the Persian name of the plant Lawsonia inermis, Fam.
Lythraceae. It is a woody shrub that grow in regions of North Africa, South Asia,
India and Sri Lanka. Nowadays it is rather frequent to see temporary "tattoos"
performed with henna. To make tattoos darker and long-lasting PPD has been
associated to henna in tattoo drawings mixtures, so obtaining "black henna". In
these years there has been a rise of contact sensitization to PPD and in medical
literature an increased number of cases have been reported on temporary henna
tattoo application. Here we review the various clinical patterns related to PPD
and henna tattoo, to investigate the possible link between clinic-morphological
pictures and the immunological response to PPD and henna. The literature
underlines that different clinical manifestations are related to black henna
containing PPD, and its derivative products may cause delayed-type as well as
immediate-type reactions. Further studies are needed to investigate the
relationship between clinical and morphological aspects of PPD contact dermatitis
and the T cell subsets predominance.
PMID- 28400709
TI - Focus on Metagenomics.
PMID- 28400707
TI - SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma.
AB - Even if severe asthma (SA) accounts for 5-10% of all cases of the disease, it is
currently a crucial unmet need, owing its difficult clinical management and its
high social costs. For this reason several networks, focused on SA have been
organized in some countries, in order to select these patients, to recognize
their clinical features, to evaluate their adherence, to classify their
biological/clinical phenotypes, to identify their eligibility to the new biologic
therapies and to quantify the costs of the disease. Aim of the present paper is
to describe the ongoing Italian Severe Asthma Network (SANI). Up today 49 centres
have been selected, widespread on the national territory. Sharing the same
diagnostic protocol, data regarding patients with SA will be collected and
processed in a web platform. After their recruitment, SA patients will be
followed in the long term in order to investigate the natural history of the
disease. Besides clinical data, the cost/benefit evaluation of the new biologics
will be verified as well as the search of peculiar biomarker(s) of the disease.
PMID- 28400708
TI - Costs and savings associated with a pharmacists prescribing for minor ailments
program in Saskatchewan.
AB - BACKGROUND: Health care systems around the world have started to develop
pharmacists prescribing for minor ailments (PPMA) programs. These programs aim to
improve the efficiency of care, reduce physician visits, and increase the
accessibility to prescription medication (Rx). This study performed an economic
impact analysis of the pharmacists prescribing for minor ailments program in
Saskatchewan. METHODS: We measured costs for the program and the alternative
scenario (i.e. no PPMA program) from a public payer and societal perspective,
using primary data on pharmacists prescribing consultations in Saskatchewan.
Furthermore, we calculated public payer and societal savings, and return on
investment ratios for the program, as well as projecting the costs and benefits
over the next 5 years. RESULTS: Overall, we found that from a societal
perspective, the Saskatchewan PPMA program saved the province approximately
$546,832 in 2014, while according to the public payer perspective, the program
was only marginally cost-saving in 2014. After 5 years of implementation, from a
societal perspective, cumulative cost savings were projected to be $3,482,660,
and the return on investment ratio was estimated to be 2.53. CONCLUSIONS: Our
results demonstrate that this type of program may prove cost-saving and lead to
improved access to the health care system in Canada, especially if savings to
society are considered. This type of PPMA program may prove economically feasible
and beneficial in many countries considering expanding pharmacists scope of
practice.
PMID- 28400710
TI - Update on the Use of Consensus Interferon in Difficult-to-Treat Hepatitis C
Patients: A Review of Selected Posters From Digestive Disease Week May 20-25,
2006 Los Angeles, Calif.With commentary by:Fred Poordad, MDCedars-Sinai Medical
CenterLos Angeles, Calif.
PMID- 28400711
TI - Cannabinoid hyperemesis and the cyclic vomiting syndrome in adults: recognition,
diagnosis, acute and long-term treatment.
AB - The cannabinoid hyperemesis syndrome (CHS) and the cyclic vomiting syndrome in
adults (CVS) are both characterized by recurrent episodes of heavy nausea,
vomiting and frequently abdominal pain. Both syndromes are barely known among
physicians. Literature is inconsistent concerning clinical features which enable
differentiation between CVS and CHS. We performed a literature review using the
LIVIVO search portal for life sciences to develop a pragmatic approach towards
these two syndromes. Our findings indicate that complete and persistent
resolution of all symptoms of the disease following cannabis cessation is the
only reliable criterion applicable to distinguish CHS from CVS. Psychiatric
comorbidities (e.g. panic attacks, depression), history of migraine attacks and
rapid gastric emptying may serve as supportive criteria for the diagnosis of CVS.
Compulsive bathing behaviour, a clinical observation previously attributed only
to CHS patients is equally present in CVS patients. Long-term follow-up is
essential in order to clearly separate CHS from CVS. However, long-term follow-up
of CVS and CHS cases is seldom. We provide a standard operating procedure
applicable to a broad spectrum of health care facilities which addresses the
major issues of CVS and CHS: awareness, diagnosis, treatment, and follow-up.
PMID- 28400712
TI - Inverted U-Shaped Curvilinear Relationship between Challenge and One's Intrinsic
Motivation: Evidence from Event-Related Potentials.
AB - The balance between task demand and one's competence is critical for the
maintenance of intrinsic motivation. According to Flow theory and Self
determination theory, optimal challenge gives rise to the maximum intrinsic
motivation, and an inverted U-shaped curvilinear relationship between perceived
challenge and one's intrinsic motivation is suggested. In order to provide direct
experimental evidences for predictions of these theories, in this study, we
employed the two-player StopWatch game that we previously designed, which made
references to the game format of a badminton tournament. According to our
manipulation, a male participant was defeated by the same-sex player paired with
him (played by a well-trained confederate of the experimenter) in two matches,
one with a wide margin (the complete defeat condition) and another with a narrow
one (the near miss condition). Participants performed better and reported to
enjoy the near miss match to a greater extent. Besides, an enlarged Stimulus
preceding negativity was elicited when participants were actively anticipating
outcomes in the near miss condition, suggesting greater anticipatory attention
toward the outcome and an enhanced intrinsic motivation to win. Thus, converging
electrophysiological evidences from this study and our former study confirmed the
inverted U-shaped curvilinear relationship between perceived challenge and one's
intrinsic motivation.
PMID- 28400713
TI - Dopamine Adaptations as a Common Pathway for Neurocognitive Impairment in
Diabetes and Obesity: A Neuropsychological Perspective.
AB - Evidence accumulates linking obesity and diabetes with cognitive dysfunction. At
present the mechanism(s) underlying these associations and the relative
contribution of diet, adiposity, and metabolic dysfunction are unknown. In this
perspective key gaps in knowledge are outlined and an initial sketch of a
neuropsychological profile is developed that points toward a critical role for
dopamine (DA) adaptations in neurocognitive impairment secondary to diabetes and
obesity. The precise mechanisms by which diet, metabolic dysfunction, and
adiposity influence the DA system to impact cognition remains unclear and is an
important direction for future research.
PMID- 28400714
TI - Deletion of TRPC6 Attenuates NMDA Receptor-Mediated Ca2+ Entry and Ca2+-Induced
Neurotoxicity Following Cerebral Ischemia and Oxygen-Glucose Deprivation.
AB - Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na+
and Ca2+ and are widely expressed in the brain. In this study, the role of TRPC6
was investigated following ischemia/reperfusion (I/R) and oxygen-glucose
deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT)
mice cortical neurons following I/R and in primary neurons with OGD, and that
deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD-
/neurotoxin-induced neuronal death. Using live-cell imaging to examine
intracellular Ca2+ levels ([Ca2+] i ), we found that OGD induced a significant
higher increase in glutamate-evoked Ca2+ influx compared to untreated control and
such an increase was reduced by TRPC6 deletion. Enhancement of TRPC6 expression
using AdCMV-TRPC6-GFP infection in WT neurons increased [Ca2+] i in response to
glutamate application compared to AdCMV-GFP control. Inhibition of N-methyl-d
aspartic acid receptor (NMDAR) with MK801 decreased TRPC6-dependent increase of
[Ca2+] i in TRPC6 infected cells, indicating that such a Ca2+ influx was NMDAR
dependent. Furthermore, TRPC6-dependent Ca2+ influx was blunted by blockade of
Na+ entry in TRPC6 infected cells. Finally, OGD-enhanced Ca2+ influx was reduced,
but not completely blocked, in the presence of voltage-dependent Na+ channel
blocker tetrodotoxin (TTX) and dl-alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid (AMPA) blocker CNQX. Altogether, we concluded that I/R-induced
brain damage was, in part, due to upregulation of TRPC6 in cortical neurons. We
postulate that overexpression of TRPC6 following I/R may induce neuronal death
partially through TRPC6-dependent Na+ entry which activated NMDAR, thus leading
to a damaging Ca2+ overload. These findings may provide a potential target for
future intervention in stroke-induced brain damage.
PMID- 28400715
TI - Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain.
AB - Key Points Oligodendrocyte precursor cells express doublecortin, a microtubule
associated protein.Oligodendrocyte precursor cells express doublecortin, but at a
lower level of expression than in neuronal precursor.Doublecortin is not
associated with a potential immature neuronal phenotype in Oligodendrocyte
precursor cells. Oligodendrocyte precursor cells (OPC) are glial cells that
differentiate into myelinating oligodendrocytes during embryogenesis and early
stages of post-natal life. OPCs continue to divide throughout adulthood and some
eventually differentiate into oligodendrocytes in response to demyelinating
lesions. There is growing evidence that OPCs are also involved in activity-driven
de novo myelination of previously unmyelinated axons and myelin remodeling in
adulthood. Considering these roles in the adult brain, OPCs are likely mobile
cells that can migrate on some distances before they differentiate into
myelinating oligodendrocytes. A number of studies have noted that OPCs express
doublecortin (DCX), a microtubule-associated protein expressed in neural
precursor cells and in migrating immature neurons. Here we describe the
distribution of DCX in OPCs. We found that almost all OPCs express DCX, but the
level of expression appears to be much lower than what is found in neural
precursor. We found that DCX is downregulated when OPCs start expressing mature
oligodendrocyte markers and is absent in myelinating oligodendrocytes. DCX does
not appear to signal an immature neuronal phenotype in OPCs in the adult mouse
brain. Rather, it could be involved either in cell migration, or as a marker of
an immature oligodendroglial cell phenotype.
PMID- 28400716
TI - Evaluation of the Display of Cognitive State Feedback to Drive Adaptive Task
Sharing.
AB - This paper presents an adaptive system intended to address workload imbalances
between pilots in future flight decks. Team performance can be maximized when
task demands are balanced within crew capabilities and resources. Good
communication skills enable teams to adapt to changes in workload, and include
the balancing of workload between team members This work addresses human factors
priorities in the aviation domain with the goal to develop concepts that balance
operator workload, support future operator roles and responsibilities, and
support new task requirements, while allowing operators to focus on the most
safety critical tasks. A traditional closed-loop adaptive system includes the
decision logic to turn automated adaptations on and off. This work takes a novel
approach of replacing the decision logic, normally performed by the automation,
with human decisions. The Crew Workload Manager (CWLM) was developed to
objectively display the workload between pilots and recommend task sharing; it is
then the pilots who "close the loop" by deciding how to best mitigate unbalanced
workload. The workload was manipulated by the Shared Aviation Task Battery (SAT
B), which was developed to provide opportunities for pilots to mitigate
imbalances in workload between crew members. Participants were put in situations
of high and low workload (i.e., workload was manipulated as opposed to being
measured), the workload was then displayed to pilots, and pilots were allowed to
decide how to mitigate the situation. An evaluation was performed that utilized
the SAT-B to manipulate workload and create workload imbalances. Overall, the
CWLM reduced the time spent in unbalanced workload and improved the crew
coordination in task sharing while not negatively impacting concurrent task
performance. Balancing workload has the potential to improve crew resource
management and task performance over time, and reduce errors and fatigue. Paired
with a real-time workload measurement system, the CWLM could help teams manage
their own task load distribution.
PMID- 28400717
TI - Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the
Reward System.
AB - Music can trigger emotional responses in a more direct way than any other
stimulus. In particular, music-evoked pleasure involves brain networks that are
part of the reward system. Furthermore, rhythmic music stimulates the basal
ganglia and may trigger involuntary movements to the beat. In the present study,
we created a continuously playing rhythmic, dance floor-like composition where
the ambient noise from the MR scanner was incorporated as an additional
instrument of rhythm. By treating this continuous stimulation paradigm as a
variant of resting-state, the data was analyzed with stochastic dynamic causal
modeling (sDCM), which was used for exploring functional dependencies and
interactions between core areas of auditory perception, rhythm processing, and
reward processing. The sDCM model was a fully connected model with the following
areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens
of both hemispheres. The resulting estimated parameters were compared to ordinary
resting-state data, without an additional continuous stimulation. Besides reduced
connectivity within the basal ganglia, the results indicated a reduced functional
connectivity of the reward system, namely the right ventral striatum/nucleus
accumbens from and to the basal ganglia and auditory network while listening to
rhythmic music. In addition, the right ventral striatum/nucleus accumbens
demonstrated also a change in its hemodynamic parameter, reflecting an increased
level of activation. These converging results may indicate that the dopaminergic
reward system reduces its functional connectivity and relinquishing its
constraints on other areas when we listen to rhythmic music.
PMID- 28400718
TI - Rab GTPases: The Key Players in the Molecular Pathway of Parkinson's Disease.
AB - Parkinson's disease (PD) is a progressive movement disorder with multiple non
motor symptoms. Although family genetic mutations only account for a small
proportion of the cases, these mutations have provided several lines of evidence
for the pathogenesis of PD, such as mitochondrial dysfunction, protein misfolding
and aggregation, and the impaired autophagy-lysosome system. Recently, vesicle
trafficking defect has emerged as a potential pathogenesis underlying this
disease. Rab GTPases, serving as the core regulators of cellular membrane
dynamics, may play an important role in the molecular pathway of PD through the
complex interplay with numerous factors and PD-related genes. This might shed new
light on the potential therapeutic strategies. In this review, we emphasize the
important role of Rab GTPases in vesicle trafficking and summarize the
interactions between Rab GTPases and different PD-related genes.
PMID- 28400719
TI - Reduction of Huntington's Disease RNA Foci by CAG Repeat-Targeting Reagents.
AB - In several human polyglutamine diseases caused by expansions of CAG repeats in
the coding sequence of single genes, mutant transcripts are detained in nuclear
RNA foci. In polyglutamine disorders, unlike other repeat-associated diseases,
both RNA and proteins exert pathogenic effects; therefore, decreases of both RNA
and protein toxicity need to be addressed in proposed treatments. A variety of
oligonucleotide-based therapeutic approaches have been developed for
polyglutamine diseases, but concomitant assays for RNA foci reduction are
lacking. Here, we show that various types of oligonucleotide-based reagents
affect RNA foci number in Huntington's disease cells. We analyzed the effects of
reagents targeting either CAG repeat tracts or specific HTT sequences in
fibroblasts derived from patients. We tested reagents that either acted as
translation blockers or triggered mRNA degradation via the RNA interference
pathway or RNase H activation. We also analyzed the effect of chemical
modifications of CAG repeat-targeting siRNAs on their efficiency in the foci
decline. Our results suggest that the decrease of RNA foci number may be
considered as a readout of treatment outcomes for oligonucleotide reagents.
PMID- 28400720
TI - Superparamagnetic Iron Oxide Nanoparticle-Mediated Forces Enhance the Migration
of Schwann Cells Across the Astrocyte-Schwann Cell Boundary In vitro.
AB - Schwann cells (SCs) are one of the most promising cellular candidates for the
treatment of spinal cord injury. However, SCs show poor migratory ability within
the astrocyte-rich central nervous system (CNS) environment and exhibit only
limited integration with host astrocytes. Our strategy for improving the
therapeutic potential of SCs was to magnetically drive SCs to migrate across the
astrocyte-SC boundary to intermingle with astrocytes. SCs were firstly magnetized
with poly-L-lysine-coated superparamagnetic iron oxide nanoparticles (SPIONs).
Internalization of SPIONs showed no effect upon the migration of SCs in the
absence of a magnetic field (MF). In contrast, magnetized SCs exhibited enhanced
migration along the direction of force in the presence of a MF. An inverted
coverslip assay showed that a greater number of magnetized SCs migrated longer
distances onto astrocytic monolayers under the force of a MF compared to other
test groups. More importantly, a confrontation assay demonstrated that magnetized
SCs intermingled with astrocytes under an applied MF. Furthermore, inhibition of
integrin activation reduced the migration of magnetized SCs within an astrocyte
rich environment under an applied MF. Thus, SPION-mediated forces could act as
powerful stimulants to enhance the migration of SCs across the astrocyte-SC
boundary, via integrin-mediated mechanotransduction, and could represent a vital
way of improving the therapeutic potential of SCs for spinal cord injuries.
PMID- 28400721
TI - MiR-384 Regulates the Th17/Treg Ratio during Experimental Autoimmune
Encephalomyelitis Pathogenesis.
AB - Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS),
during which IL-17-producing CD4+ T helper (Th17) cells accumulate in the central
nervous system (CNS). In this study, we identified levels of miR-384 as
significantly increased in mice with experimental autoimmune encephalomyelitis
(EAE), an animal model of MS. Over-expression of miR-384 in vivo led to severe
EAE, characterized by exacerbated demyelination, and increased inflammatory cell
infiltration of the spinal cord; inhibition of miR-384 reversed these changes.
Both the percentage of Th17, and ratio of Th17/regulatory T (Treg), cells were
elevated in miR-384-transfected EAE mice, which was consistent with the observed
upregulation of expression of IL-17 and the Th17 lineage-specific transcription
factor, RORgammat. Importantly, transfer of miR-384 overexpressing naive T cells
from wild-type (WT) to Rag1-/- mice, which are deficient in functional autologous
T and B cells, led to aggravated EAE pathogenesis, while an miR-384 inhibited
group was protected from EAE. Moreover, miR-384 promoted differentiation of naive
T cells into Th17 cells in vitro. Furthermore, target prediction and dual
luciferase reporter assays demonstrated that suppressor of cytokine signaling 3
(SOCS3), a gene encoding protein with an established role in Th17
differentiation, was a direct target of miR-384. Our results demonstrate an
important role for miR-384 in regulation of the Th17/Treg ratio during the
pathogenesis of EAE, indicating that this molecule may have potential as a
biomarker and/or therapeutic target in MS.
PMID- 28400722
TI - Sex Differences in the Physiological and Behavioral Effects of Chronic Oral
Methylphenidate Treatment in Rats.
AB - Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit
Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access
drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic
profile of treated patients. This study assessed sex differences in response to
this treatment. Male and female Sprague Dawley rats were assigned to one of three
treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD)
MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during
the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each
day. Throughout 3 months of treatment, rats were monitored for body weight, food
intake, and fluid intake; as well as tested for open field behavior, circadian
activity, novel object recognition, and social interaction. Chronic MP treated
rats exhibited reduced fluid intake during distinct treatment weeks to a greater
extent in males, and reduced total fluid intake in males only. HD MP treatment
decreased body weight in both sexes, while HD MP increased total food intake in
females only, likely to offset energy deficits resulting from MP-induced
hyperactivity. LD and HD MP increased locomotor activity in the open field,
particularly in females and during later treatment weeks. MP dose-dependently
increased activity during the dark cycle of circadian testing in females, while
in males hyperactivity was only exhibited by HD rats. HD MP increased center
activity to a greater extent in males, while MP increased rearing behavior in
females only. MP had no effect on social behavior or novel object recognition in
either sex. This study concludes that chronic oral MP treatment at clinically
relevant dosages has significant effects on food intake, body weight, open field
behavior, and wake cycle activity. Particularly marked sex differences were
apparent for locomotor activity, with females being significantly more sensitive
to the hyperactivating effects of the drug. These findings suggest that chronic
MP exposure beginning in adolescence can have significant behavioral effects that
are both dose- and sex-dependent, and raise concerns regarding the reversibility
of these effects post-discontinuation of treatment.
PMID- 28400723
TI - Electrophysiological Correlates of Familiarity and Recollection in Associative
Recognition: Contributions of Perceptual and Conceptual Processing to
Unitization.
AB - It is generally accepted that associative recognition memory is supported by
recollection. In addition, recent research indicates that familiarity can support
associative memory, especially when two items are unitized into a single item.
Both perceptual and conceptual manipulations can be used to unitize items, but
few studies have compared these two methods of unitization directly. In the
present study, we investigated the effects of familiarity and recollection on
successful retrieval of items that were unitized perceptually or conceptually.
Participants were instructed to remember either a Chinese two-character compound
or unrelated word-pairs, which were presented simultaneously or sequentially.
Participants were then asked to recognize whether word-pairs were intact or
rearranged. Event-related potential (ERP) recordings were performed during the
recognition phase of the study. Two-character compounds were better discriminated
than unrelated word-pairs and simultaneous presentation was found to elicit
better discrimination than sequential presentation for unrelated word-pairs only.
ERP recordings indicated that the early intact/rearranged effects (FN400),
typically associated with familiarity, were elicited in compound word-pairs with
both simultaneous and sequential presentation, and in simultaneously presented
unrelated word-pairs, but not in sequentially presented unrelated word-pairs. In
contrast, the late positive complex (LPC) effects associated with recollection
were elicited in all four conditions. Together, these results indicate that while
the engagement of familiarity in associative recognition is affected by both
perceptual and conceptual unitization, conceptual unitization promotes a higher
level of unitization (LOU). In addition, the engagement of recollection was not
affected by unitized manipulations. It should be noted, however, that due to
experimental design, the effects presented here may be due to semantic rather
than episodic memory and future studies should take this into consideration when
manipulating rearranged pairs.
PMID- 28400724
TI - Influence of Cervical Spine Mobility on the Focal and Postural Components of the
Sit-to-Stand Task.
AB - The aim of this study was to determine the influence of cervical spine mobility
on the focal and postural components of the sit-to-stand transition, which
represent the preparatory and execution phases of the task, respectively. Sixteen
asymptomatic female participants (22 +/- 3 years, 163 +/- 0,06 cm, 57,5 +/- 5
kg), free of any neurological or musculoskeletal disorders, performed six trials
of the sit-to-stand task at maximum speed, in four experimental conditions
varying the mobility of the cervical spine by means of three different splints. A
six-channel force plate, which collected the reaction forces and moments applied
at its top surface, was used to calculate the center of pressure displacements
along the anterior-posterior and medial-lateral axes. The local accelerations of
the head, spine, and pelvis, were assessed by three pairs of accelerometers,
oriented along the vertical and anterior-posterior axes. Restriction of cervical
spine mobility resulted in an increased duration of the focal movement,
associated with longer and larger postural adjustments. These results suggest
that restricted cervical spine mobility impairs the posturo-kinetic capacity
during the sit-to-stand task, leading to a lower motor performance and a
reorganization of the anticipatory postural adjustments. In a clinical context,
it might be assumed that preserving the articular free play of the cervical spine
might be useful to favor STS performance and autonomy.
PMID- 28400725
TI - Cortical Mechanisms of Tongue Sensorimotor Functions in Humans: A Review of the
Magnetoencephalography Approach.
AB - The tongue plays important roles in a variety of critical human oral functions,
including speech production, swallowing, mastication and respiration. These
sophisticated tongue movements are in part finely regulated by cortical
entrainment. Many studies have examined sensorimotor processing in the limbs
using magnetoencephalography (MEG), which has high spatiotemporal resolution.
Such studies have employed multiple methods of analysis, including somatosensory
evoked fields (SEFs), movement-related cortical fields (MRCFs), event-related
desynchronization/synchronization (ERD/ERS) associated with somatosensory
stimulation or movement and cortico-muscular coherence (CMC) during sustained
movement. However, the cortical mechanisms underlying the sensorimotor functions
of the tongue remain unclear, as contamination artifacts induced by stimulation
and/or muscle activity within the orofacial region complicates MEG analysis in
the oral region. Recently, several studies have obtained MEG recordings from the
tongue region using improved stimulation methods and movement tasks. In the
present review, we provide a detailed overview of tongue sensorimotor processing
in humans, based on the findings of recent MEG studies. In addition, we review
the clinical applications of MEG for sensory disturbances of the tongue caused by
damage to the lingual nerve. Increased knowledge of the physiological and
pathophysiological mechanisms underlying tongue sensorimotor processing may
improve our understanding of the cortical entrainment of human oral functions.
PMID- 28400726
TI - Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord
Injury.
AB - Spinal cord injury (SCI) remains a debilitating condition for which there is no
cure. In addition to loss of somatic sensorimotor functions, SCI is also commonly
associated with impairment of autonomic function. Importantly, cough dysfunction
due to paralysis of expiratory muscles in combination with respiratory
insufficiency can render affected individuals vulnerable to respiratory
morbidity. Failure to clear sputum can aggravate both risk for and severity of
respiratory infections, accounting for frequent hospitalizations and even
mortality. Recently, epidural stimulation of the lower thoracic spinal cord has
been investigated as novel means for restoring cough by evoking expiratory muscle
contraction to generate large positive airway pressures and expulsive air flow.
This review article discusses available preclinical and clinical evidence,
current challenges and clinical potential of lower thoracic spinal cord
stimulation (SCS) for restoring cough in individuals with SCI.
PMID- 28400727
TI - Effects of Aging in Multisensory Integration: A Systematic Review.
AB - Multisensory integration (MSI) is the integration by the brain of environmental
information acquired through more than one sense. Accurate MSI has been shown to
be a key component of successful aging and to be crucial for processes underlying
activities of daily living (ADLs). Problems in MSI could prevent older adults
(OA) to age in place and live independently. However, there is a need to know how
to assess changes in MSI in individuals. This systematic review provides an
overview of tests assessing the effect of age on MSI in the healthy elderly
population (aged 60 years and older). A literature search was done in Scopus.
Articles from the earliest records available to January 20, 2016, were eligible
for inclusion if assessing effects of aging on MSI in the healthy elderly
population compared to younger adults (YA). These articles were rated for risk of
bias with the Newcastle-Ottawa quality assessment. Out of 307 identified research
articles, 49 articles were included for final review, describing 69 tests. The
review indicated that OA maximize the use of multiple sources of information in
comparison to YA (20 studies). In tasks that require more cognitive function, or
when participants need to adapt rapidly to a situation, or when a dual task is
added to the experiment, OA have problems selecting and integrating information
properly as compared to YA (19 studies). Additionally, irrelevant or wrong
information (i.e., distractors) has a greater impact on OA than on YA (21
studies). OA failing to weigh sensory information properly, has not been
described in previous reviews. Anatomical changes (i.e., reduction of brain
volume and differences of brain areas' recruitment) and information processing
changes (i.e., general cognitive slowing, inverse effectiveness, larger time
window of integration, deficits in attentional control and increased noise at
baseline) can only partly explain the differences between OA and YA regarding
MSI. Since we have an interest in successful aging and early detection of MSI
issues in the elderly population, the identified tests form a good starting point
to develop a clinically useful toolkit to assess MSI in healthy OA.
PMID- 28400728
TI - Socio-Economic Inequalities, Out-of-Pocket Payment and Consumers' Satisfaction
with Primary Health Care: Data from the National Adult Consumers' Satisfaction
Survey in Serbia 2009-2015.
PMID- 28400730
TI - Biocompatible Colloidal Suspensions Based on Magnetic Iron Oxide Nanoparticles:
Synthesis, Characterization and Toxicological Profile.
AB - The use of magnetic iron oxide nanoparticles in biomedicine has evolved intensely
in the recent years due to the multiple applications of these nanomaterials,
mainly in domains like cancer. The aim of the present study was: (i) to develop
biocompatible colloidal suspensions based on magnetic iron oxide nanoparticles as
future theranostic tools for skin pathology and (ii) to test their effects in
vitro on human keratinocytes (HaCat cells) and in vivo by employing an animal
model of acute dermal toxicity. Biocompatible colloidal suspensions were obtained
by coating the magnetic iron oxide nanoparticles resulted during the solution
combustion synthesis with a double layer of oleic acid, as innovative procedure
in increasing bioavailability. The colloidal suspensions were characterized in
terms of dynamic light scattering (DLS) and transmission electron microscopy
(TEM). The in vitro effects of these suspensions were tested by means of Alamar
blue assay and the noxious effects at skin level were measured using non-invasive
methods. The in vitro results indicated a lack of toxicity on normal human cells
induced by the iron oxide nanoparticles colloidal suspensions after an exposure
of 24 h to different concentrations (5, 10, and 25 MUg.mL-1). The dermal acute
toxicity test showed that the topical applications of the colloidal suspensions
on female and male SKH-1 hairless mice were not associated with significant
changes in the quality of barrier skin function.
PMID- 28400731
TI - IL-1 Inhibition May Have an Important Role in Treating Refractory Kawasaki
Disease.
AB - Kawasaki disease (KD) is an acute inflammatory vasculitis occurring in young
children before 5 years and representing at this age, the main cause of acquired
heart disease. A single infusion of 2 g/kg of intravenous immunoglobulins along
with aspirin has reduced the frequency of coronary artery aneurysms from 25 to
5%. However, 10-20% of patients do not respond to standard treatment and have an
increased risk of cardiac complications and death. The development of more potent
therapeutic approaches of KD is an urgent need. Phenotypical and immunological
similarities between KD and systemic juvenile idiopathic arthritis led to the
hypothesis that KD could be considered as an autoinflammatory disease. New
insights regarding KD's pathogenesis have merged from the combination of genetic
and transcriptomic data revealing the key role of interleukin-1 (IL-1) signaling
in the pathogenesis of the vasculitis. Once activated, IL-1alpha and IL-1beta
trigger a local proinflammatory environment-inducing vasodilatation and
attracting monocytes and neutrophils to sites causing tissue damage and stress.
Both IL-1alpha and IL-1beta have been shown to induce myocarditis and aneurysm
formation in Lactobacillus casei cell-wall extract mouse model of KD; both being
successfully improved with IL-1 blockade treatment such as anakinra. Treatment
failure in patients with the high-risk inositol-triphosphate 3-kinase C genotype
was associated with highest basal and stimulated intracellular calcium levels,
increased cellular production of IL-1beta, and IL-18, and higher circulating
levels of both cytokines. Three clinical trials of IL-1 blockade enrolling KD
patients are currently being conducted in Western Europe and in USA, they could
change KD outcome.
PMID- 28400729
TI - Prostate Cancer Stem Cells and Nanotechnology: A Focus on Wnt Signaling.
AB - Prostate cancer is the most common cancer among men worldwide. However, current
treatments for prostate cancer patients in advanced stage often fail because of
relapse. Prostate cancer stem cells (PCSCs) are resistant to most standard
therapies, and are considered to be a major mechanism of cancer metastasis and
recurrence. In this review, we summarized current understanding of PCSCs and
their self-renewal signaling pathways with a specific focus on Wnt signaling.
Although multiple Wnt inhibitors have been developed to target PCSCs, their
application is still limited by inefficient delivery and toxicity in vivo.
Recently, nanotechnology has opened a new avenue for cancer drug delivery, which
significantly increases specificity and reduces toxicity. These nanotechnology
based drug delivery methods showed great potential in targeting PCSCs. Here, we
summarized current advancement of nanotechnology-based therapeutic strategies for
targeting PCSCs and highlighted the challenges and perspectives in designing
future therapies to eliminate PCSCs.
PMID- 28400733
TI - Optimization of Huang-Lian-Jie-Du-Decoction for Ischemic Stroke Treatment and
Mechanistic Study by Metabolomic Profiling and Network Analysis.
AB - Optimal drug proportions and mechanism deciphering of multicomponent drugs are
critical for developing novel therapies to cope with complex diseases, such as
stroke. In the present study, orthogonal experimental design was applied to
explore the optimal proportion of the four component herbs in Huang-Lian-Jie-Du
Decoction (HLJDD) on the treatment of ischemic stroke. The treatment efficacies
and mechanisms were assessed using global and amino acids (AAs) targeted
metabolomics, as well as correlation network analysis. The global NMR
metabolomics results revealed that AAs metabolism was significantly perturbed in
middle cerebral artery occlusion rats. The levels of 23 endogenous AAs were then
subjected to HPLC-QTOF-MS/MS analysis. These results complemented with
neurobehavioral evaluations, cerebral infarct assessments, biochemical
evaluations, histological inspections and immunohistochemistry observations
strongly demonstrated that HLJDD with optimal proportion of 6 (Rhizoma coptidis):
4 (Radix scutellariae): 1 (Cortex phellodendr): 3 (Fructus Gardeniae) had the
best efficacy on ischemic stroke, which could be ascribed to its modulation on AA
metabolism. This integrated metabolomics approach showed the potential and
applicable in deciphering the complex mechanisms of traditional Chinese medicine
formulae on the treatment of complicated diseases, which provided new means to
assess the treatment effects of herb combinations and to further development of
drugs or therapies based on these formulae.
PMID- 28400732
TI - How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL
1beta.
AB - One of the main clinical features characterizing crystal-induced inflammation is
its spontaneous resolution. The aim of this review is to outline the various
factors involved in the self-limiting course of crystal-induced inflammation
focusing on their effect on IL-1beta production. Endogenous molecules that are
induced or locally recruited by the process itself, inhibitory proteins naturally
present in the joint and exogenous dietary factors are discussed. Aside from the
classical well-known molecules involved in the resolution of crystal-induced
acute attack such as TGFbeta, IL-10, IL-1Ra, and lipoproteins, particular
attention is paid to recently uncovered mechanisms such as the aggregation of
neutrophil extracellular traps, the release of ectosomes from neutrophil surface,
and alpha-1-anti-trypsin-mediated IL-1 inhibition.
PMID- 28400734
TI - Embodied Organization of Octopus vulgaris Morphology, Vision, and Locomotion.
PMID- 28400735
TI - A Novel Stopped-Flow Assay for Quantitating Carbonic-Anhydrase Activity and
Assessing Red-Blood-Cell Hemolysis.
AB - We report a novel carbonic-anhydrase (CA) assay and its use for quantitating red
blood-cell (RBC) lysis during stopped-flow (SF) experiments. We combine two
saline solutions, one containing HEPES/pH 7.03 and the other, ~1% CO2/44 mM
[Formula: see text]/pH 8.41, to generate an out-of-equilibrium CO2/[Formula: see
text] solution containing ~0.5% CO2/22 [Formula: see text]/pH ~7.25 (10 degrees
C) in the SF reaction cell. CA catalyzes relaxation of extracellular pH to ~7.50:
[Formula: see text] + H+ -> CO2 + H2O. Proof-of-concept studies (no intact RBCs)
show that the pH-relaxation rate constant (kDeltapH)-measured via pyranine
fluorescence-rises linearly with increases in [bovine CAII] or [murine-RBC
lysate]. The y-intercept (no CA) was kDeltapH = 0.0183 s-1. Combining increasing
amounts of murine-RBC lysate with ostensibly intact RBCs (pre-SF hemolysis ?0.4%)
fixing total [hemoglobin] at 2.5 MUM in the reaction cell to simulate hemolysis
from ostensibly 0 to 100%-causes kDeltapH to increase linearly. This y-intercept
(0% lysate/100% ostensibly intact RBCs) was kDeltapH = 0.0820 s-1, and the
maximal kDeltapH (100% lysate/0% intact RBCs) was 1.304 s-1. Thus, mean percent
hemolysis in the reaction cell was ~4.9%. Phenol-red absorbance assays yield
indistinguishable results. The increase from 0.4 to 4.9% presumably reflects
mechanical RBC disruption during rapid mixing. In all fluorescence studies, the
CA blocker acetazolamide reduces kDeltapH to near-uncatalyzed values, implying
that all CA activity is extracellular. Our lysis assay is simple, sensitive, and
precise, and will be valuable for correcting for effects of lysis in
physiological SF experiments. The underlying CA assay, applied to blood plasma,
tissue-culture media, and organ perfusates could assess lysis in a variety of
applications.
PMID- 28400736
TI - Nicotine Effects and Receptor Expression on Human Spermatozoa: Possible
Neuroendocrine Mechanism.
AB - The aim of this experimental study was to investigate the mechanism by which
nicotine (NIC) alters spermatozoa and to evaluate the expression of nicotinic
receptors (nAChR) subunits in human spermatozoa. We analyzed 30 healthy
normozoospermic men. Spermatozoa were incubated with NIC 100 ng/ml and the nAChR
antagonist, hexamethonium (HEX) (0, 100, 1,000, 10,000 ng/ml) for 3 and 24 h. The
following sperm parameters evaluated: (a) progressive motility; (b) mitochondrial
membrane potential (MMP); (c) chromatin compactness; (d) externalization of
phosphatidylserine (PS); (e) late apoptosis; (f) viability; (g) DNA
fragmentation; (h) degree of lipid peroxidation (LP) by flow cytometry; (i) nAChR
subunits expression by quantitative Real Time PCR and (j) protein expression
evaluation by Western blot analysis. HEX fully antagonized the effects of NIC
both after 3 and 24 h of incubation with significant improvement (p < 0.05) of
sperm progressive motility, MMP, abnormal chromatin compactness, PS
externalization, late apoptosis and DNA fragmentation, already at the
concentration of HEX 100 ng/ml. The degree of LP increased after incubation with
NIC in raw semen but this effect was fully antagonized (p < 0.05) by HEX after 3
and 24 h of incubation. Finally, 8 nAChR subunits mRNA (alpha1, alpha3, alpha4,
alpha6, alpha7, beta2, beta4, and delta) were found expressed in all samples
examined, but only alpha7 subunit is translated, making an homomer receptor, in
non-smokers subjects. The effects of NIC on sperm function are mediated by
interaction with a specific nicotinic receptor. The presence of nAChR subunits
suggests the presence of a neuroendocrine mechanism on human spermatozoa.
PMID- 28400737
TI - Reduced Resting-State Functional Connectivity in Current and Recovered
Restrictive Anorexia Nervosa.
AB - Functional connectivity studies based on resting-state functional magnetic
resonance imaging (rs-fMRI) have shown alterations in brain networks associated
with self-referential processing, cognitive control, and somatosensory processing
in anorexia nervosa (AN). This study aimed to further investigate the functional
connectivity of resting-state networks (RSNs) in homogenous subsamples of
individuals with restrictive AN (current and recovered) and the relationship this
has with core eating disorder psychopathology. rs-fMRI scans were obtained from
12 female individuals with restrictive AN, 14 females recovered from restrictive
AN, and 16 female healthy controls. Independent components analysis revealed a
set of functionally relevant RSNs, previously reported in the literature. Dual
regression analysis showed decreased temporal coherence within the lateral visual
and auditory RSNs in individuals with current AN and those recovered from AN
compared to healthy individuals. This decreased connectivity was also found in
regions associated with somatosensory processing, and is consistent with reduced
interoceptive awareness and body image perception, characteristic of AN.
Widespread gray matter (GM) reductions were also found in both the AN groups, and
differences in functional connectivity were no longer significant when GM maps
were added as a covariate in the dual regression analysis. This raises the
possibility that deficits in somatosensory and interoceptive processing observed
in AN may be in part underpinned or exacerbated by GM reductions.
PMID- 28400738
TI - Grammar Is Differentially Impaired in Subgroups of Autism Spectrum Disorders:
Evidence from an Investigation of Tense Marking and Morphosyntax.
AB - Deficits in the production of verbal inflection (tense marking, or finiteness)
are part of the Optional Infinitive (OI) stage of typical grammatical
development. They are also a hallmark of language impairment: they have been used
as biomarkers in guiding genetic studies of Specific Language Impairment (SLI),
and have also been observed in autism spectrum disorders (ASD). To determine the
detailed nature of finiteness abilities in subgroups of ASD [autism with impaired
language (ALI) vs. autism with normal language (ALN)], we compared tense marking
abilities in 46 children with ALI and 37 children with ALN with that of two
groups of nonverbal mental age (MA) and verbal MA-matched typically developing
(TD) controls, the first such study described in the literature. Our
participants' performance on two elicited production tasks, probing third-person
singular -s and past tense -ed, from the Rice/Wexler Test of Early Grammatical
Impairment (TEGI, Rice and Wexler, 2001), revealed extensive deficits in the ALI
group: their ability to correctly mark tense was significantly worse than their
much younger TD controls', and significantly worse than that of the ALN group. In
contrast, the ALN group performed similarly to their TD controls. We found good
knowledge of the meaning of tense, and of case and agreement, in both ASD groups.
Similarly, both ASD groups showed distributions of null or overt subjects with
nonfinite and finite verbs in line with those found in young TD children. A key
difference, however, was that the ALI group used (rather than simply omitted) the
wrong tense in some sentences, a feature not reported in the OI stage for TD or
SLI children. Our results confirm a clear distinction in the morphosyntactic
abilities of the two subgroups of children with ASD: the language system
responsible for finiteness in the ALN group seems to be functioning comparably to
that of the TD children, whereas the ALI group, despite showing knowledge of case
and agreement, seems to experience an extensive grammatical deficit with respect
to finiteness which does not seem to improve with age. Crucially, our ALI group
seems to have worse grammatical abilities even than those reported for SLI.
PMID- 28400739
TI - Toward a Psychology of Social Change: A Typology of Social Change.
AB - Millions of people worldwide are affected by dramatic social change (DSC). While
sociological theory aims to understand its precipitants, the psychological
consequences remain poorly understood. A large-scale literature review pointed to
the desperate need for a typology of social change that might guide theory and
research toward a better understanding of the psychology of social change. Over
5,000 abstracts from peer-reviewed articles were assessed from sociological and
psychological publications. Based on stringent inclusion criteria, a final 325
articles were used to construct a novel, multi-level typology designed to
conceptualize and categorize social change in terms of its psychological threat
to psychological well-being. The typology of social change includes four social
contexts: Stability, Inertia, Incremental Social Change and, finally, DSC. Four
characteristics of DSC were further identified: the pace of social change,
rupture to the social structure, rupture to the normative structure, and the
level of threat to one's cultural identity. A theoretical model that links the
characteristics of social change together and with the social contexts is also
suggested. The typology of social change as well as our theoretical proposition
may serve as a foundation for future investigations and increase our
understanding of the psychologically adaptive mechanisms used in the wake of DSC.
PMID- 28400740
TI - C-Command in the Grammars of Children with High Functioning Autism.
AB - A recent study questioned the adherence of children with Autism Spectrum
Disorders (ASD) to a linguistic constraint on the use of reflexive pronouns
(Principle A) in sentences like Bart's dad is touching himself. This led
researchers to question whether children with ASD are able to compute the
hierarchical structural relationship of c-command, and raised the possibility
that the children rely on a linear strategy for reference assignment. The current
study investigates the status of c-command in children with ASD by testing their
interpretation of sentences like (1) and (2) that tease apart use of c-command
and a linear strategy for reference assignment. The girl who stayed up late will
not get a dime or a jewel (C-command)The girl who didn't go to sleep will get a
dime or a jewel (Non C-command) These examples both contain negation (not or
didn't) and disjunction (or). In (1), negation c-commands the disjunction phrase,
yielding a conjunctive entailment. This gives rise to the meaning that the girl
who stayed up late won't get a dime and she won't get a jewel. In (2), negation
is positioned inside a relative clause and it does not c-command disjunction.
Therefore, no conjunctive entailment follows. Thus, (2) is true if the girl just
gets a dime or just a jewel, or possibly both. If children with ASD lack c
command, then (1) will not give rise to a conjunctive entailment. In this case,
children might rely on a linear strategy for reference assignment. Since negation
precedes disjunction in both (1) and (2), they might be interpreted in a similar
manner. Likewise, children who show knowledge of c-command should perform well on
sentences governed by Principle A. These hypotheses were tested in experiments
with 12 Australian children with HFA, aged 5;4 to 12;7, and 12 typically
developing controls, matched on non-verbal IQ. There was no significant
difference in the pattern of responses by children with HFA and the control
children on either (1) and (2) or the Principle A sentences. The findings provide
preliminary support for the proposal that knowledge of c-command and Principle A
is intact in HFA children.
PMID- 28400741
TI - Future Time Perspective in the Work Context: A Systematic Review of Quantitative
Studies.
AB - A core construct in the lifespan theory of socioemotional selectivity, future
time perspective (FTP) refers to individuals' perceptions of their remaining time
in life. Its adaptation to the work context, occupational future time perspective
(OFTP), entails workers' perceptions of remaining time and opportunities in their
careers. Over the past decade, several quantitative studies have investigated
antecedents and consequences of general FTP and OFTP in the work context (i.e.,
FTP at work). We systematically review and critically discuss this literature on
general FTP (k = 17 studies) and OFTP (k = 16 studies) and highlight implications
for future research and practice. Results of our systematic review show that, in
addition to its strong negative relationship with age, FTP at work is also
associated with other individual (e.g., personality traits) and contextual
variables (e.g., job characteristics). Moreover, FTP at work has been shown to
mediate and moderate relationships of individual and contextual antecedents with
occupational well-being, as well as motivational and behavioral outcomes. As a
whole, findings suggest that FTP at work is an important variable in the field of
work and aging, and that future research should improve the ways in which FTP at
work is measured and results on FTP at work are reported.
PMID- 28400742
TI - Whose Expertise Is It? Evidence for Autistic Adults as Critical Autism Experts.
AB - Autistic and non-autistic adults' agreement with scientific knowledge about
autism, how they define autism, and their endorsement of stigmatizing conceptions
of autism has not previously been examined. Using an online survey, we assessed
autism knowledge and stigma among 636 adults with varied relationships to autism,
including autistic people and nuclear family members. Autistic participants
exhibited more scientifically based knowledge than others. They were more likely
to describe autism experientially or as a neutral difference, and more often
opposed the medical model. Autistic participants and family members reported
lower stigma. Greater endorsement of the importance of normalizing autistic
people was associated with heightened stigma. Findings suggest that autistic
adults should be considered autism experts and involved as partners in autism
research.
PMID- 28400743
TI - Contrasting Complement Control, Temporal Adjunct Control and Controlled Verbal
Gerund Subjects in ASD: The Role of Contextual Cues in Reference Assignment.
AB - This study examines two complex syntactic dependencies (complement control and
sentence-final temporal adjunct control) and one pragmatic dependency (controlled
verbal gerund subjects) in children with ASD. Sixteen high-functioning (HFA)
children (aged 6-16) with a diagnosis of autism and no language impairment,
matched on age, gender and non-verbal MA to one TD control group, and on age,
gender and verbal MA to another TD control group, undertook three picture
selection tasks. Task 1 measured their base-line interpretations of the empty
categories (ec). Task 2 preceded these sentence sets with a weakly established
topic cueing an alternative referent and Task 3 with a strongly established topic
cueing an alternative referent. In complement control (Ron persuaded Hermione ec
to kick the ball) and sentence-final temporal adjunct control (Harry tapped Luna
while ec feeding the owl), the reference of the ec is argued to be related
obligatorily to the object and subject respectively. In controlled verbal-gerund
subjects (VGS) (ec Rowing the boat clumsily made Luna seasick), the ec's
reference is resolved pragmatically. Referent choices across the three tasks were
compared. TD children chose the object uniformly in complement control across all
tasks but in adjunct control, preferences shifted toward the object in Task 3. In
controlled VGSs, they exhibited a strong preference for an internal-referent
interpretation in Task 1, which shifted in the direction of the cues in Tasks 2
and 3. HFA children gave a mixed performance. They patterned with their TD
counterparts on complement control and controlled VGSs but performed marginally
differently on adjunct control: no TD groups were influenced by the weakly
established topic in Task 2 but all groups were influenced by the strongly
established topic in Task 3. HFA children were less influenced than the TD
children, resulting in their making fewer object choices overall but revealing
parallel patterns of performance. In this first study of three sub-types of
control in ASD, we demonstrate that HFA children consult the same pragmatic cues
to the same degree as TD children, in spite of the diverse pragmatic deficits
reported for this population.
PMID- 28400744
TI - A Psychosocial Approach to Understanding Underground Spaces.
AB - With a growing need for usable land in urban areas, subterranean development has
been gaining attention. While construction of large underground complexes is not
a new concept, our understanding of various socio-cultural aspects of staying
underground is still at a premature stage. With projected emergence of
underground built environments, future populations may spend much more of their
working, transit, and recreational time in underground spaces. Therefore, it is
essential to understand the challenges and advantages that such environments have
to improve the future welfare of users of underground spaces. The current paper
discusses various psycho-social aspects of underground spaces, the impact they
can have on the culture shared among the occupants, and possible solutions to
overcome some of these challenges.
PMID- 28400745
TI - Minority Dissent and Social Acceptance in Collaborative Learning Groups.
AB - The main aim of this paper is to test the extent to which social acceptance
moderates the impact of minority dissent on group cognitive complexity (GCC). We
hypothesize that divergent views expressed by a minority increase GCC especially
when the group climate is open to divergent contributions (e.g., a socially
accepting group climate). We also hypothesize that group size has a non-linear
association with GCC in such a way that GCC increases as group size increases
from low to average and then GCC decreases as group size further increases from
average to high. We test these hypotheses in a sample of 537 students (258 women,
with an average age of 23.35) organized in 92 groups that have worked together in
the same group throughout the semester, and show that: (1) group size has a
decreasing positive association with GCC, (2) both minority dissent and social
acceptance are beneficial for GCC and (3) groups with the highest GCC are those
that experience minority dissent and develop a socially accepting climate (in
which group members can equally participate to the task), allowing the majority
to process the dissenting views extensively.
PMID- 28400746
TI - Commentary: Mobile and Interactive Media Use by Young Children: The Good, the
Bad, and the Unknown.
PMID- 28400747
TI - The Positive Effects of Trait Emotional Intelligence during a Performance Review
Discussion - A Psychophysiological Study.
AB - Performance review discussions of real manager-subordinate pairs were examined in
two studies to investigate the effects of trait emotional intelligence (EI) on
dyad member's felt and expressed emotions. Altogether there were 84 managers and
122 subordinates in two studies using 360 measured and self-reported trait EI.
Facial electromyography, and frontal electroencephalography (EEG) asymmetry were
collected continuously. Manager's high trait EI was related to increased positive
valence emotional facial expressions in the dyad during the discussions. The
managers also had more EEG frontal asymmetry indicating approach motivation, than
the subordinates. In addition, actor and partner effects and actor * partner
interactions, and interactions between the role and actor or partner effect of
trait EI were observed. Both actor and partner trait EI were related to more
positive self-reported emotional valence. The results imply that trait EI has a
role in organizational social interaction.
PMID- 28400748
TI - Short-Term Exposure of Paddy Soil Microbial Communities to Salt Stress Triggers
Different Transcriptional Responses of Key Taxonomic Groups.
AB - Soil salinization due to seawater intrusion along coastal areas is an increasing
threat to rice cultivation worldwide. While the detrimental impact on rice growth
and yield has been thoroughly studied, little is known about how severe salinity
affects structure and function of paddy soil microbial communities. Here, we
examined their short-term responses to half- and full-strength seawater salinity
in controlled laboratory experiments. Slurry microcosms were incubated under
anoxic conditions, with rice straw added as carbon source. Stress exposure time
was for 2 days after a pre-incubation period of 7 days. Relative to the control,
moderate (300 mM NaCl) and high (600 mM NaCl) salt stress suppressed both net
consumption of acetate and methane production by 50% and 70%, respectively.
Correspondingly, community-wide mRNA expression decreased by 50-65%, with
significant changes in relative transcript abundance of family-level groups. mRNA
turnover was clearly more responsive to salt stress than rRNA dynamics. Among
bacteria, Clostridiaceae were most abundant and the only group whose
transcriptional activity was strongly stimulated at 600 mM NaCl. In particular,
clostridial mRNA involved in transcription/translation, fermentation, uptake and
biosynthesis of compatible solutes, and flagellar motility was significantly
enriched in response salt stress. None of the other bacterial groups were able to
compete at 600 mM NaCl. Their responses to 300 mM NaCl were more diverse.
Lachnospiraceae increased, Ruminococcaceae maintained, and Peptococcaceae,
Veillonellaceae, and Syntrophomonadaceae decreased in relative mRNA abundance.
Among methanogens, Methanosarcinaceae were most dominant. Relative to other
family-level groups, salt stress induced a significant enrichment of transcripts
related to the CO dehydrogenase/acetyl-coenzyme A synthase complex,
methanogenesis, heat shock, ammonium uptake, and thermosomes, but the absolute
abundance of methanosarcinal mRNA decreased. Most strikingly, the transcriptional
activity of the Methanocellaceae was completely suppressed already at 300 mM
NaCl. Apparently, the key taxonomic groups involved in the methanogenic breakdown
of plant polymers significantly differ in their ability to cope with severe salt
stress. Presumably, this different ability is directly linked to differences in
their genetic potential and metabolic flexibility to reassign available energy
resources for cellular adaptation to salt stress.
PMID- 28400749
TI - Radiative Energy Budgets of Phototrophic Surface-Associated Microbial Communities
and their Photosynthetic Efficiency Under Diffuse and Collimated Light.
AB - We investigated the radiative energy budgets of a heterogeneous photosynthetic
coral reef sediment and a compact uniform cyanobacterial biofilm on top of
coastal sediment. By combining electrochemical, thermocouple and fiber-optic
microsensor measurements of O2, temperature and light, we could calculate the
proportion of the absorbed light energy that was either dissipated as heat or
conserved by photosynthesis. We show, across a range of different incident light
regimes, that such radiative energy budgets are highly dominated by heat
dissipation constituting up to 99.5% of the absorbed light energy. Highest
photosynthetic energy conservation efficiency was found in the coral sediment
under low light conditions and amounted to 18.1% of the absorbed light energy.
Additionally, the effect of light directionality, i.e., diffuse or collimated
light, on energy conversion efficiency was tested on the two surface-associated
systems. The effects of light directionality on the radiative energy budgets of
these phototrophic communities were not unanimous but, resulted in local spatial
differences in heat-transfer, gross photosynthesis, and light distribution. The
light acclimation index, Ek, i.e., the irradiance at the onset of saturation of
photosynthesis, was >2 times higher in the coral sediment compared to the biofilm
and changed the pattern of photosynthetic energy conservation under light
limiting conditions. At moderate to high incident irradiances, the photosynthetic
conservation of absorbed energy was highest in collimated light; a tendency that
changed in the biofilm under sub-saturating incident irradiances, where higher
photosynthetic efficiencies were observed under diffuse light. The aim was to
investigate how the physical structure and light propagation affected energy
budgets and light utilization efficiencies in loosely organized vs. compact
phototrophic sediment under diffuse and collimated light. Our results suggest
that the optical properties and the structural organization of phytoelements are
important traits affecting the photosynthetic efficiency of biofilms and
sediments.
PMID- 28400750
TI - Methylation on RNA: A Potential Mechanism Related to Immune Priming within But
Not across Generations.
AB - Invertebrate immune priming is a growing field in immunology. This phenomenon
refers to the ability of invertebrates to generate a more vigorous immune
response to a second encounter with a specific pathogen and can occur within and
across generations. Although the precise mechanism has not been elucidated, it
has been suggested that methylation of DNA is a cornerstone for this phenomenon.
Here, using a novel method of analytical chemistry (a reversed-phase liquid
chromatography procedure) and the beetle Tenebrio molitor as a model system, we
did not find evidence to support this hypothesis taking into account the
percentage of methylated cytosine entities in DNA (5mdC) within or across
generations. However, we found a lower percentage of methylated cytosine entities
in RNA (5mC) within but not across generations in immune priming experiments with
adults against the bacteria Micrococcus lysodeikticus and larvae against the
fungus Metarhizium anisopliae. To our knowledge, this is the first report
suggesting a role of differential methylation on RNA during immune priming within
generations.
PMID- 28400751
TI - Ethanolic Extract of Melia Fructus Has Anti-influenza A Virus Activity by
Affecting Viral Entry and Viral RNA Polymerase.
AB - Meliae Fructus (MF) is the dried ripe fruit of Melia toosendan Siebold et
Zuccarini, Meliaceae family. MF is widely used in traditional medicine to treat
inflammation and helminthic infection and has anti-bacterial, anti-oxidant, anti
cancer, anti-inflammatory, and analgesic activities. However, potential anti
influenza properties of MF have yet to be investigated. We determined whether an
ethanolic extract of MF (EMF) has anti-viral activity via an EMF pre-, co-, and
post-treatment assay, using the Influenza A/PR/8/34 and H3N2 virus on Madin-Darby
canine kidney (MDCK) cells. The EMF had anti-influenza virus activity in pre- and
co-treated cells in a dose-dependent manner, but not in post-treated cell. EMF
inhibited the activity of hemagglutinin (HA) and neuraminidase (NA) of influenza
virus. EMF inhibited viral HA, nucleoprotein (NP), matrix protein 2 (M2), non
structural protein 1 (NS1), polymerase acidic protein (PA), polymerase basic
protein 1 (PB1), and polymerase basic protein 2 (PB2) mRNA synthesis at 5 h post
infection (hpi), however, the levels of PA, PB1, and PB2 mRNA were increased in
pre- and co-EMF treated cells compared with control virus-infected and EMF post
treated cells at 18 hpi. The level of M2 protein expression was also decreased
upon pre- and co-treatment with EMF. The PA protein was accumulated and localized
in not only the nucleus but also the cytoplasm of virus-infected MDCK cells at 18
hpi. Pre-EMF treatment inhibited the expression of pAKT, which is induced by
influenza virus infection, at the stage of virus entry. We also found that
treatment of EMF up-regulated the antiviral protein Mx1, which may play a partial
role in inhibiting influenza virus infection in pre- and co-EMF treated MDCK
cells. In summary, these results strongly suggested that an ethanolic extract of
Meliae Fructus inhibited influenza A virus infection by affecting viral entry, PA
proteins of the RNA polymerase complex, and Mx1 induction and may be a potential
and novel anti-influenza agent.
PMID- 28400752
TI - Expression and Function of Different Guanine-Plus-Cytosine Content 16S rRNA Genes
in Haloarcula hispanica at Different Temperatures.
AB - The halophilic archaeon Haloarcula hispanica harbors three ribosomal RNA (rRNA)
operons (rrnA, rrnB, and rrnC) that contain the 16S rRNA genes rrsA, rrsB, and
rrsC, respectively. Although rrsB and rrsC (rrsBC) have almost identical
sequences, the rrsA and rrsBC sequences differ by 5.4%, and they differ by 2.5%
with respect to guanine-plus-cytosine content (PGC). The strong correlation
between the typical growth temperatures of archaea and PGC of their 16S rRNA
genes suggests that H. hispanica may harbor different 16S rRNA genes having
different PGC to maintain rapid growth in a wide range of temperatures. We
therefore performed reverse transcription-coupled quantitative PCR to assess
expression levels of rrsA (PGC, 58.9%) and rrsBC (PGC, 56.4-56.5%) at various
temperatures. The expression ratio of rrsA to rrsBC increased with culture
temperature. Mutants with complete deletions of one or two of the three rRNA
operons were constructed and their growth rates at different temperatures
compared to that of the wild-type. The growth characteristics of the rRNA operon
single-mutant strains were indistinguishable from the wild-type. The rRNA operon
double-mutant strains maintained the same temperature range as wild-type but
displayed reduced growth rates. In particular, the double-mutant strains grew
much slower than wild-type at low temperature related to minimum growth
temperature of the wild-type. On the other hand, at physiologically high
temperatures the wild-type and the double-mutant strain which harbors only rrnA
with high-PGCrrsA grew significantly faster than the double-mutant strain which
harbors only rrnC with low-PGCrrsC. These findings suggest the importance of 16S
rRNAs transcribed from rrsA with high-PGC in maintaining rapid growth of this
halophilic archaeon at raised growth temperatures.
PMID- 28400754
TI - Mineral Ecology: Surface Specific Colonization and Geochemical Drivers of Biofilm
Accumulation, Composition, and Phylogeny.
AB - This study tests the hypothesis that surface composition influences microbial
community structure and growth of biofilms. We used laboratory biofilm reactors
(inoculated with a diverse subsurface community) to explore the phylogenetic and
taxonomic variability in microbial communities as a function of surface type
(carbonate, silicate, aluminosilicate), media pH, and carbon and phosphate
availability. Using high-throughput pyrosequencing, we found that surface type
significantly controlled ~70-90% of the variance in phylogenetic diversity
regardless of environmental pressures. Consistent patterns also emerged in the
taxonomy of specific guilds (sulfur-oxidizers/reducers, Gram-positives,
acidophiles) due to variations in media chemistry. Media phosphate availability
was a key property associated with variation in phylogeny and taxonomy of whole
reactors and was negatively correlated with biofilm accumulation and alpha
diversity (species richness and evenness). However, mineral-bound phosphate
limitations were correlated with less biofilm. Carbon added to the media was
correlated with a significant increase in biofilm accumulation and overall alpha
diversity. Additionally, planktonic communities were phylogenetically distant
from those in biofilms. All treatments harbored structurally (taxonomically and
phylogenetically) distinct microbial communities. Selective advantages within
each treatment encouraged growth and revealed the presence of hundreds of
additional operational taxonomix units (OTU), representing distinct consortiums
of microorganisms. Ultimately, these results provide evidence that mineral/rock
composition significantly influences microbial community structure, diversity,
membership, phylogenetic variability, and biofilm growth in subsurface
communities.
PMID- 28400753
TI - The Helicobacter pylori J99 jhp0106 Gene, under the Control of the CsrA/RpoN
Regulatory System, Modulates Flagella Formation and Motility.
AB - CsrA has been shown to positively control the expression of flagella-related
genes, including flaA and flaB, through regulating expression of an alternative
sigma factor RpoN in Helicobacter pylori J99. Here, we aimed to characterize the
CsrA regulatory system by comparative transcriptomic analysis carried out with
RNA-seq on strain J99 and a csrA mutant. Fifty-three genes in the csrA mutant
were found to be differentially expressed compared with the wild-type. Among CsrA
regulated genes, jhp0106, with unclear function, was found located downstream of
flaB in the J99 genome. We hypothesized that flaB-jhp0106 is in an operon under
the control of RpoN binding to the flaB promoter. The RT-qPCR results showed the
expression of jhp0106 was decreased 76 and 92% in the csrA and rpoN mutants,
respectively, compared to the wild-type. Moreover, mutations of the RpoN binding
site in the flaB promoter region resulted in decreased expression of flaB and
jhp0106 and deficient motility. Three-dimensional structure modeling results
suggested that Jhp0106 was a glycosyltransferase. The role of jhp0106 in H.
pylori was further investigated by constructing the jhp0106 mutant and revertant
strains. A soft-agar motility assay and transmission electron microscope were
used to determine the motility and flagellar structure of examined strains, and
the results showed the loss of motility and flagellar structure in jhp0106 mutant
J99. In conclusion, we found jhp0106, under the control of the CsrA/RpoN
regulatory system, plays a critical role in H. pylori flagella formation.
PMID- 28400755
TI - Comparative Evaluation of Four Bacteria-Specific Primer Pairs for 16S rRNA Gene
Surveys.
AB - Bacterial taxonomic community analyses using PCR-amplification of the 16S rRNA
gene and high-throughput sequencing has become a cornerstone in microbiology
research. To reliably detect the members, or operational taxonomic units (OTUs),
that make up bacterial communities, taxonomic surveys rely on the use of the most
informative PCR primers to amplify the broad range of phylotypes present in up-to
date reference databases. However, primers specific for the domain Bacteria were
often developed some time ago against database versions that are now out of date.
Here we evaluated the performance of four bacterial primers for characterizing
complex microbial communities in explosives contaminated and non-contaminated
forest soil and by in silico evaluation against the current SILVA123 database.
Primer pair 341f/785r produced the highest number of bacterial OTUs, phylogenetic
richness, Shannon diversity, low non-specificity and most reproducible results,
followed by 967f/1391r and 799f/1193r. Primer pair 68f/518r showed overall low
coverage and a bias toward Alphaproteobacteria. In silico, primer pair 341f/785r
showed the highest coverage of the domain Bacteria (96.1%) with no obvious bias
toward the majority of bacterial species. This suggests the high utility of
primer pair 341f/785r for soil and plant-associated bacterial microbiome studies.
PMID- 28400757
TI - Streptococcus agalactiae Causing Neonatal Infections in Portugal (2005-2015):
Diversification and Emergence of a CC17/PI-2b Multidrug Resistant Sublineage.
AB - The molecular characterization of 218 GBS isolates recovered from neonatal
invasive infections in Portugal in 2005-2015 revealed the existence of a small
number of genetically distinct lineages that were present over a significant time
span. Serotypes III and Ia were dominant in the population, together accounting
for >80% of the isolates. Clonal complex 17 included 50% of all isolates,
highlighting the importance of the hypervirulent genetic lineage represented by
serotype III ST17/rib/PI-1+PI-2b. Serotype Ia was represented mainly by ST23,
previously reported as dominant among invasive disease in non-pregnant adults in
Portugal, but also by ST24, showing an increased frequency among late-onset
disease. Overall erythromycin resistance was 16%, increasing during the study
period (p < 0.001). Macrolide resistance was overrepresented among CC1 and CC19
isolates (p < 0.001 and p = 0.008, respectively). While representatives of the
hypervirulent CC17 lineage were mostly susceptible to macrolides, we identified
for the first time in Europe a recently emerging sublineage characterized by the
loss of PI-1 (CC17/PI-2b), simultaneously resistant to macrolides, lincosamides,
and tetracycline, also exhibiting high-level resistance to streptomycin and
kanamycin. The stability and dominance of CC17 among neonatal invasive infections
in the past decades indicates that it is extremely well adapted to its niche;
however emerging resistance in this genetic background may have significant
implications for the prevention and management of GBS disease.
PMID- 28400758
TI - Leptospira Infection Interferes with the Prothrombinase Complex Assembly during
Experimental Leptospirosis.
AB - Leptospirosis is a worldwide zoonotic and neglected infectious disease of human
and veterinary concern, caused by pathogenic Leptospira species. Although
bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is
not completely understood. In severe infections, modulation of hemostasis by
pathogens is an important virulence mechanism, and hemostatic impairments such as
coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze
the coagulation status of experimentally infected hamsters in an attempt to
determine coagulation interferences and the origin of leptospirosis hemorrhagic
symptomatology. Hamsters were experimentally infected with L. interrogans. The
lungs, kidneys, and livers were collected for culture, histopathology, and
coagulation assays. L. interrogans infection disturbs normal coagulation in the
organs of animals. Our results suggest the presence of a thrombin-like factor or
FX activator, which is able to activate FII in the leptospirosis organ extracts.
The activity of those factors is accelerated in the prothrombinase complex.
Additionally, we show for the first time that live leptospires act as a surface
for the prothrombinase complex assembly. Our results contribute to the
understanding of leptospirosis pathophysiological mechanisms and may open new
routes for the discovery of novel treatments in the severe manifestations of the
disease.
PMID- 28400756
TI - Antibody Engineering for Pursuing a Healthier Future.
AB - Since the development of antibody-production techniques, a number of
immunoglobulins have been developed on a large scale using conventional methods.
Hybridoma technology opened a new horizon in the production of antibodies against
target antigens of infectious pathogens, malignant diseases including autoimmune
disorders, and numerous potent toxins. However, these clinical humanized or
chimeric murine antibodies have several limitations and complexities. Therefore,
to overcome these difficulties, recent advances in genetic engineering techniques
and phage display technique have allowed the production of highly specific
recombinant antibodies. These engineered antibodies have been constructed in the
hunt for novel therapeutic drugs equipped with enhanced immunoprotective
abilities, such as engaging immune effector functions, effective development of
fusion proteins, efficient tumor and tissue penetration, and high-affinity
antibodies directed against conserved targets. Advanced antibody engineering
techniques have extensive applications in the fields of immunology,
biotechnology, diagnostics, and therapeutic medicines. However, there is limited
knowledge regarding dynamic antibody development approaches. Therefore, this
review extends beyond our understanding of conventional polyclonal and monoclonal
antibodies. Furthermore, recent advances in antibody engineering techniques
together with antibody fragments, display technologies, immunomodulation, and
broad applications of antibodies are discussed to enhance innovative antibody
production in pursuit of a healthier future for humans.
PMID- 28400759
TI - Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic
Burkitt Lymphoma.
AB - Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated
with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections.
Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which
is caused by a translocation of an Ig enhancer in approximation to the myc gene.
While whole genome/transcriptome sequencing methods have been used to define
driver mutations and transcriptional dysregulation, microRNA (miRNA)
dysregulation and differential expression has yet to be fully characterized. We
hypothesized that both human and EBV miRNAs contribute to eBL clinical
presentation, disease progression, and poor outcomes. Using sensitive and precise
deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples
and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa
miR-10a-5p was found to be differentially expressed (DE), being down-regulated in
jaw tumors relative to abdominal and in non-survivors compared to survivors. We
also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL
samples. However, we did not find any significant associations regarding initial
patient outcome or anatomical presentation. Gene ontology analysis and pathway
enrichment of previously validated targets of miR-10a-5p suggest that it can
promote tumor cell survival as well as aid in evasion of apoptosis. To examine
miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise
correlation coefficient analysis on the expression levels of all its validated
targets. We found a significant enrichment of correlated target genes consistent
with miR-10a-5p impacting expression. The functions of genes and their
correlation fit with multiple target genes impacting tumor resilience. The
observed downregulation of miR-10a and associated genes suggests a role for miRNA
in eBL patient outcomes and has potential as a predictive biomarker that warrants
further investigation.
PMID- 28400760
TI - Aeromonas Diversity and Antimicrobial Susceptibility in Freshwater-An Attempt to
Set Generic Epidemiological Cut-Off Values.
AB - The importance of the role of environment in the dissemination of antimicrobial
resistant bacteria is now well recognized. Thus, bacterial indicators to monitor
the phenomena are required. The Aeromonas genus is autochthonous in the aquatic
environment and easy to detect in any water type, such as freshwater, or
wastewater. These microorganisms are also causing infections in humans and
animals (including fish). Furthermore, as Aeromonas spp. is able to acquire
antimicrobial resistance mechanisms, it is candidate for indicator bacteria to
follow antimicrobial resistance dissemination in aquatic environments.
Unfortunately, to date, interpretation criteria for Aeromonas spp. for
antimicrobial susceptibility tests are scarce in the literature. No
epidemiological cut-off values for Aeromonas are currently available at EUCAST to
interpret Minimum Inhibitory Concentrations (MIC). The only interpretation
criteria available are clinical breakpoints from CLSI that are adapted from
Enterobacteriaceae. Based on the results of MIC distributions obtained for a
collection of environmental isolates of Aeromonas, this study aimed at proposing
tentative epidemiological cut-off values (COWT) for Aeromonas spp. assessing
whether the genus is an acceptable level of definition. Thus, 233 isolates
collected from 16 rivers were identified at species level using Maldi-Tof
(Bruker). Eleven different species were identified, the most abundant were A.
bestiarum (n = 54), A. salmonicida (n = 45), A. sobria (n = 41), and A.
eucrenophila (n = 37). 96-well micro-plates containing different concentrations
of 15 antimicrobials, namely cefotaxime, ceftazidime, chloramphenicol, colistin,
enrofloxacin, erythromycin, florfenicol, flumequine, gentamicin, nalidixic acid,
oxolinic acid, streptomycin, temocillin, tetracycline, and trimethoprim
sulfamethoxazole, were prepared. The broth micro-dilution method was used to
determine the antimicrobial susceptibility of each isolate. The estimation of
COWT values was satisfactory obtained at genus level for all antimicrobials
except cefotaxime and erythromycin. This first step is an invitation for other
research teams to increase the amount of antimicrobial resistance data collected.
Then, robustness of our proposed provisional generic epidemiological cut-off
values could be assessed by testing antimicrobial susceptibility of various
Aeromonas collections.
PMID- 28400761
TI - Brucella Genital Tropism: What's on the Menu.
PMID- 28400762
TI - Production and Reutilization of Fluorescent Dissolved Organic Matter by a Marine
Bacterial Strain, Alteromonas macleodii.
AB - The recalcitrant fraction of marine dissolved organic matter (DOM) plays an
important role in carbon storage on the earth's surface. Bacterial production of
recalcitrant DOM (RDOM) has been proposed as a carbon sequestration process. It
is still unclear whether bacterial physiology can affect RDOM production. In this
study, we conducted a batch culture using the marine bacterial isolate
Alteromonas macleodii, a ubiquitous gammaproteobacterium, to evaluate the linkage
between bacterial growth and DOM production. Glucose (1 mmol C L-1) was used as
the sole carbon source, and the bacterial number, the DOM concentration in terms
of carbon, and the excitation-emission matrices (EEMs) of DOM were monitored
during the 168-h incubation. The incubation period was partitioned into the
exponential growth (0-24 h) and stationary phases (24-168 h) based on the growth
curve. Although the DOM concentration decreased during the exponential growth
phase due to glucose consumption, it remained stable during the stationary phase,
corresponding to approximately 4% of the initial glucose in terms of carbon.
Distinct fluorophores were not evident in the EEMs at the beginning of the
incubation, but DOM produced by the strain exhibited five fluorescent peaks
during exponential growth. Two fluorescent peaks were similar to protein-like
fluorophores, while the others could be categorized as humic-like fluorophores.
All fluorophores increased during the exponential growth phase. The tryptophan
like fluorophore decreased during the stationary phase, suggesting that the
strain reused the large exopolymer. The tyrosine-like fluorophore seemed to be
stable during the stationary phase, implying that the production of tyrosine
containing small peptides through the degradation of exopolymers was correlated
with the reutilization of the tyrosine-like fluorophore. Two humic-like
fluorophores that showed emission maxima at the longer wavelength (525 nm)
increased during the stationary phase, while the other humic-like fluorophore,
which had a shorter emission wavelength (400 nm) and was categorized as
recalcitrant, was stable. These humic-like fluorophore behaviors during
incubation indicated that the composition of bacterial humic-like fluorophores,
which were unavailable to the strain, differed between growth phases. Our results
suggest that bacterial physiology can affect RDOM production and accumulation in
the ocean interior.
PMID- 28400763
TI - Editorial: Emerging Enterobacteriaceae Infections: Antibiotic Resistance and
Novel Treatment Options.
PMID- 28400764
TI - Antimicrobial Resistance of Salmonella enterica Serovar Typhimurium in Shanghai,
China.
AB - We aimed to analyze the antimicrobial resistance phenotypes and to elucidate the
molecular mechanisms underlying resistance to cephalosporins, ciprofloxacin, and
azithromycin in Salmonella enterica serovar Typhimurium isolates identified from
patients with diarrhea in Shanghai. The isolates showed high rates of resistance
to traditional antimicrobials, and 20.6, 12.7, and 5.5% of them exhibited
decreased susceptibility to cephalosporins, ciprofloxacin, and azithromycin,
respectively. Notably, 473 (84.6%) isolates exhibited multidrug resistance (MDR),
including 161 (28.8%) isolates that showed an ACSSuT profile. Twenty-two MDR
isolates concurrently exhibited decreased susceptibility to cephalosporins and
ciprofloxacin, and six of them were co-resistant to azithromycin. Of all the 71
isolates with decreased susceptibility to ciprofloxacin, 65 showed at least one
mutation (D87Y, D87N, or D87G) in gyrA, among which seven isolates simultaneously
had mutations of parC (S80R) (n = 6) or parC (T57S/S80R) (n = 1), while 49
isolates with either zero or one mutation in gyrA contained plasmid-mediated
quinolone resistance (PMQR) genes including qnrB, qnrS, and aac(6')-Ib-cr. Among
the 115 cephalosporin-resistant isolates, the most common ESBL gene was blaCTX-M,
followed by blaTEM-1, blaOXA-1, and blaSHV -12. Eight subtypes of blaCTX-M were
identified and blaCTX-M-14 (n = 22) and blaCTX-M-55 (n = 31) were found to be
dominant. To the best of our knowledge, this is the first report of the presence
of blaCTX-M-123 and blaCTX-M-125 in S. Typhimurium. Besides, mphA gene was
identified in 15 of the 31 azithromycin-resistant isolates. Among the 22 isolates
with reduced susceptibility to cephalosporins and ciprofloxacin, 15 contained
ESBL and PMQR genes. Coexistence of these genes lead to the emergence of MDR and
the transmission of them will pose great difficulties in S. Typhimurium
treatments. Therefore, surveillance for these MDR isolates should be enhanced.
PMID- 28400765
TI - Role of Bacillus licheniformis VS16-Derived Biosurfactant in Mediating Immune
Responses in Carp Rohu and its Application to the Food Industry.
AB - Multifarious applications of Bacillus licheniformis VS16-derived biosurfactant
were explored. Labeo rohita fingerlings were injected intraperitoneally with 0.1
mL of phosphate-buffered saline (PBS) containing purified biosurfactant at 0
(control), 55 (S55), 110 (S110), 220 (S220), or 330 (S330) MUg mL-1
concentrations. Various immunological parameters and the expression of immune
related genes were measured at 7, 14, and 21 days post-administration (dpa). At
21 dpa, fish were challenged with Aeromonas hydrophila and mortality was recorded
for 14 days. Immune parameters such as lysozyme levels (39.29 +/- 2.14 U mL-1),
alternative complement pathway (61.21 +/- 2.38 U mL-1), and phagocytic activities
(33.37 +/- 1.2%) were maximum (P < 0.05) in the S220 group at 14 dpa; but
immunoglobulin levels (11.07 +/- 0.83 mg mL-1) were highest in the S220 group at
7 dpa, compared to that in controls. Activities of digestive enzymes (amylase,
protease, and lipase) were higher (P < 0.05) in the S220 and S330 groups than in
the control group. Regarding cytokine gene expression, pro-inflammatory cytokines
(TNF-alpha and IL-1beta) were down-regulated (P < 0.05) in the S220 and S330
groups. Expression of IL-10, TGF-beta, and IKB-alpha were up-regulated in the
S220 and S330 groups at 14 dpa, with the highest levels in the S220 group. The
expression of NF-kappaB p65 and IKK-beta were down-regulated in treatment groups,
and were lowest (P < 0.05) in the S220 group. The highest post-challenge survival
rate (72.7%) was recorded in S220 group. Further, the potential of this substance
to inhibit biofilm formation, and heavy metal removal from vegetables were also
evaluated. Biosurfactant was effective in inhibiting biofilm formation up to
54.71 +/- 1.27%. Moreover, it efficiently removed cadmium (Cd) from tested
vegetables such as carrot, radish, ginger, and potato, with the highest removal
efficiency (60.98 +/- 1.29%) recorded in ginger contaminated with Cd.
Collectively, these results suggest that isolated biosurfactant could be used in
the aquaculture industry, in addition to its potential application to the food
industry.
PMID- 28400766
TI - Function and Structural Organization of the Replication Protein of Bamboo mosaic
virus.
AB - The genus Potexvirus is one of the eight genera belonging to the family
Alphaflexiviridae according to the Virus Taxonomy 2015 released by International
Committee on Taxonomy of Viruses (www.ictvonline.org/index.asp). Currently, the
genus contains 35 known species including many agricultural important viruses,
e.g., Potato virus X (PVX). Members of this genus are characterized by flexuous,
filamentous virions of 13 nm in diameter and 470-580 nm in length. A potexvirus
has a monopartite positive-strand RNA genome, encoding five open-reading frames
(ORFs), with a cap structure at the 5' end and a poly(A) tail at the 3' end.
Besides PVX, Bamboo mosaic virus (BaMV) is another potexvirus that has received
intensive attention due to the wealth of knowledge on the molecular biology of
the virus. In this review, we discuss the enzymatic activities associated with
each of the functional domains of the BaMV replication protein, a 155-kDa
polypeptide encoded by ORF1. The unique cap formation mechanism, which may be
conserved across the alphavirus superfamily, is particularly addressed. The
recently identified interactions between the replication protein and the plant
host factors are also described.
PMID- 28400767
TI - The Periplasmic Chaperone Network of Campylobacter jejuni: Evidence that SalC
(Cj1289) and PpiD (Cj0694) Are Involved in Maintaining Outer Membrane Integrity.
AB - The outer membrane (OM) of Gram-negative pathogenic bacteria is a key structure
in host-pathogen interactions that contains a plethora of proteins, performing a
range of functions including adhesion, nutrient uptake, export of effectors and
interaction with innate and adaptive components of the immune system. In
addition, the OM can exclude drugs and thus contribute to antimicrobial
resistance. The OM of the food-borne pathogen Campylobacter jejuni contains
porins, adhesins and other virulence factors that must be specifically localized
to this membrane, but the protein sorting mechanisms involved are only partially
understood. In particular, chaperones are required to ferry OM proteins across
the periplasm after they emerge from the Sec translocation system. The SurA
related chaperone PEB4 (Cj0596) is the only protein with a proven role in OM
biogenesis and integrity in C. jejuni. In this work, we have constructed a set of
isogenic deletion mutants in genes encoding both known and predicted chaperones
(cj0596, cj0694, cj1069, cj1228c, and cj1289) using NCTC 11168H as the parental
strain. These mutants were characterized using a range of assays to determine
effects on growth, agglutination, biofilm formation, membrane permeability and
hydrophobicity. We focused on Cj1289 and Cj0694, which our previous work
suggested possessed both chaperone and peptidyl-proyl cis/trans isomerase
(PPIase) domains. Mutants in either cj1289 or cj0694 showed growth defects,
increased motility, agglutination and biofilm formation and severe OM
permeability defects as measured by a lysozyme accessibility assay, that were
comparable to those exhibited by the isogenic peb4 mutant. 2D-gel comparisons
showed a general decrease in OM proteins in these mutants. We heterologously
overproduced and purified Cj0694 and obtained evidence that this protein was an
active PPIase, as judged by its acceleration of the refolding rate of reduced and
alkylated ribonuclease T1 and that it also possessed holdase-type chaperone
activity. Cj0694 is most similar to the PpiD class of chaperones but is unusual
in possessing PPIase activity. Taken together, our data show that in addition to
PEB4, Cj1289 (SalC; SurA-like chaperone) and Cj0694 (PpiD) are also key proteins
involved in OM biogenesis and integrity in C. jejuni.
PMID- 28400768
TI - The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against
Cryptococcus neoformans.
AB - Cryptococcus neoformans is the most lethal pathogen of the central nervous
system. The gold standard treatment of cryptococcosis, a combination of
amphotericin B with 5-fluorocytosine, involves broad toxicity, high costs, low
efficacy, and limited worldwide availability. Although the need for new
antifungals is clear, drug research and development (R&D) is costly and time
consuming. Thus, drug repurposing is an alternative to R&D and to the currently
available tools for treating fungal diseases. Here we screened a collection of
compounds approved for use in humans seeking for those with anti-cryptococcal
activity. We found that benzimidazoles consist of a broad class of chemicals
inhibiting C. neoformans growth. Mebendazole and fenbendazole were the most
efficient antifungals showing in vitro fungicidal activity. Since previous
studies showed that mebendazole reaches the brain in biologically active
concentrations, this compound was selected for further studies. Mebendazole
showed antifungal activity against phagocytized C. neoformans, affected
cryptococcal biofilms profoundly and caused marked morphological alterations in
C. neoformans, including reduction of capsular dimensions. Amphotericin B and
mebendazole had additive anti-cryptococcal effects. Mebendazole was also active
against the C. neoformans sibling species, C. gattii. To further characterize the
effects of the drug a random C. gattii mutant library was screened and indicated
that the antifungal activity of mebendazole requires previously unknown
cryptococcal targets. Our results indicate that mebendazole is as a promising
prototype for the future development of anti-cryptococcal drugs.
PMID- 28400769
TI - Role of Modulator of Inflammation Cyclooxygenase-2 in Gammaherpesvirus Mediated
Tumorigenesis.
AB - Chronic inflammation is recognized as a threat factor for cancer progression.
Release of inflammatory molecules generates microenvironment which is highly
favorable for development of tumor, cancer progression and metastasis. In cases
of latent viral infections, generation of such a microenvironment is one of the
major predisposing factors related to virus mediated tumorigenesis. Among various
inflammatory mediators implicated in pathological process associated with cancer,
the cyclooxygenase (COX) and its downstream effector molecules are of greater
significance. Though the role of infectious agents in causing inflammation
leading to transformation of cells has been more or less well established,
however, the mechanism by which inflammation in itself modulates the events in
life cycle of infectious agent is not very much clear. This is specifically
important for gammaherpesviruses infections where viral life cycle is
characterized by prolonged periods of latency when the virus remains hidden,
immunologically undetectable and expresses only a very limited set of genes.
Therefore, it is important to understand the mechanisms for role of inflammation
in virus life cycle and tumorigenesis. This review is an attempt to summarize the
latest findings highlighting the significance of COX-2 and its downstream
signaling effectors role in life cycle events of gammaherpesviruses leading to
progression of cancer.
PMID- 28400770
TI - Antibacterial Action of Jineol Isolated from Scolopendra subspinipes mutilans
against Selected Foodborne Pathogens.
AB - This study was undertaken to assess the antibacterial potential of 3,8
dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans
against selected foodborne pathogens Escherichia coli O157:H7 and Staphylococcus
aureus KCTC-1621. Jineol at the tested concentration (50 MUL; corresponding to
250 MUg/disk) exhibited significant antibacterial effects as a diameter of
inhibition zones (11.6-13.6 mm), along with minimum inhibitory concentration
(MIC) and minimum bactericidal concentration values found in the range of (62.5
125 MUg/mL) and (125-250 MUg/mL), respectively. Jineol also exhibited significant
antibacterial effects as confirmed by the reduction in bacterial cell
viabilities, increasing release of potassium (K+) ions (650 and 700 mmole/L) and
260 nm materials (optical density: 2.98-3.12) against both the tested pathogens,
E. coli O157:H7 and S. aureus KCTC-1621, respectively. Moreover, changes in the
cell wall morphology of E. coli O157:H7 and S. aureus KCTC-1621 cells treated
with jineol at MIC further confirmed its inhibitory potential against the tested
pathogens, suggesting its role as an effective antimicrobial to control foodborne
pathogens.
PMID- 28400771
TI - Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and
Infection during Erythrocytic Stage.
AB - Irrespective of various efforts, malaria persist the most debilitating effect in
terms of morbidity and mortality. Moreover, the existing drugs are also
vulnerable to the emergence of drug resistance. To explore the potential targets
for designing the most effective antimalarial therapies, it is required to focus
on the facts of biochemical mechanism underlying the process of parasite survival
and disease pathogenesis. This review is intended to bring out the existing
knowledge about the functions and components of the major signaling pathways such
as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling,
serving the various aspects of the parasitic asexual stage and highlighted the
Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and
molecular events in cytoadhesion, which elicit the host immune response. This
discussion will facilitate a look over essential components for parasite survival
and disease progression to be implemented in discovery of novel antimalarial
drugs and vaccines.
PMID- 28400772
TI - Sphingolipids Are Dual Specific Drug Targets for the Management of Pulmonary
Infections: Perspective.
AB - Sphingolipids are the major constituent of the mucus secreted by the cells of
epithelial linings of lungs where they maintain the barrier functions and prevent
microbial invasion. Sphingolipids are interconvertible, and their primary and
secondary metabolites have both structural and functional roles. Out of several
sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central
molecules and decisive for sphingolipid signaling. These are produced by
enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either
biological or physiological stresses. S1P and ceramide rheostat are important for
the progression of various pathologies, which are manifested by inflammatory
cascade. S1P is a well-established secondary messenger and associated with
various neuronal, metabolic, and inflammatory diseases other than respiratory
infections such as Chlamydia pneumoniae, Streptococcus pneumoniae, and
Mycobacterium tuberculosis. These pathogens are known to exploit sphingolipid
metabolism for their opportunistic survival. Decreased sphingosine kinase
activity/S1P content in the lung and peripheral blood of tuberculosis patients
clearly indicated a dysregulation of sphingolipid metabolism during infection and
suggest that sphingolipid metabolism is important for management of infection by
the host. Our previous study has demonstrated that gain of SK-1 activity is
important for the maturation of phagolysosomal compartment, innate activation of
macrophages, and subsequent control of mycobacterial replication/growth in
macrophages. Furthermore, S1P-mediated amelioration of lung pathology and disease
severity in TB patients is believed to be mediated by the selective activation or
rearrangement of various S1P receptors (S1PR) particularly S1PR2, which has been
effective in controlling respiratory fungal pathogens. Therefore, such
specificity of S1P-S1PR would be paramount for triggering inflammatory events,
subsequent activation, and fostering bactericidal potential in macrophages for
the control of TB. In this review, we have discussed and emphasized that
sphingolipids may represent effective novel, yet dual specific drug targets for
controlling pulmonary infections.
PMID- 28400773
TI - Can the Responses of Photosynthesis and Stomatal Conductance to Water and
Nitrogen Stress Combinations Be Modeled Using a Single Set of Parameters?
AB - Accurately predicting photosynthesis in response to water and nitrogen stress is
the first step toward predicting crop growth, yield and many quality traits under
fluctuating environmental conditions. While mechanistic models are capable of
predicting photosynthesis under fluctuating environmental conditions, simplifying
the parameterization procedure is important toward a wide range of model
applications. In this study, the biochemical photosynthesis model of Farquhar,
von Caemmerer and Berry (the FvCB model) and the stomatal conductance model of
Ball, Woodrow and Berry which was revised by Leuning and Yin (the BWB-Leuning-Yin
model) were parameterized for Lilium (L. auratum * speciosum "Sorbonne") grown
under different water and nitrogen conditions. Linear relationships were found
between biochemical parameters of the FvCB model and leaf nitrogen content per
unit leaf area (Na), and between mesophyll conductance and Na under different
water and nitrogen conditions. By incorporating these Na-dependent linear
relationships, the FvCB model was able to predict the net photosynthetic rate
(An) in response to all water and nitrogen conditions. In contrast, stomatal
conductance (gs) can be accurately predicted if parameters in the BWB-Leuning-Yin
model were adjusted specifically to water conditions; otherwise gs was
underestimated by 9% under well-watered conditions and was overestimated by 13%
under water-deficit conditions. However, the 13% overestimation of gs under water
deficit conditions led to only 9% overestimation of An by the coupled FvCB and
BWB-Leuning-Yin model whereas the 9% underestimation of gs under well-watered
conditions affected little the prediction of An. Our results indicate that to
accurately predict An and gs under different water and nitrogen conditions, only
a few parameters in the BWB-Leuning-Yin model need to be adjusted according to
water conditions whereas all other parameters are either conservative or can be
adjusted according to their linear relationships with Na. Our study exemplifies a
simplified procedure of parameterizing the coupled FvCB and gs model that is
widely used for various modeling purposes.
PMID- 28400774
TI - Elite Haplotypes of a Protein Kinase Gene TaSnRK2.3 Associated with Important
Agronomic Traits in Common Wheat.
AB - Plant-specific protein kinase SnRK2s play crucial roles in response to various
environmental stimuli. TaSnRK2.3, a SnRK2 member, was involved in the response to
multiple abiotic stresses in wheat. To facilitate the use of TaSnRK2.3 in wheat
breeding, the three genomic sequences of TaSnRK2.3, originating from the A, B,
and D genomes of hexaploid wheat, were obtained. Sequence polymorphism assays
showing 4 and 10 variations were detected at TaSnRK2.3-1A and at TaSnRK2.3-1B,
respectively, yet no variation was identified at TaSnRK2.3-1D. Three haplotypes
for A genome, and two main haplotypes for B genome of TaSnRK2.3 were identified
in 32 genotypes. Functional markers (2.3AM1, 2.3AM2, 2.3BM1, 2.3BM2) were
successfully developed to distinguish different haplotypes. Association analysis
was performed with the general linear model in TASSEL 2.1. The results showed
that both TaSnRK2.3-1A and TaSnRK2.3-1B were significantly associated with plant
height (PH), length of peduncle and penultimate node, as well as 1,000-grain
weight (TGW) under different environments. Additionally, TaSnRK2.3-1B was
significantly associated with stem water-soluble carbohydrates at flowering and
mid-grain filling stages. Hap-1A-1 had higher TGW and lower PH; Hap-1B-1 had
higher TGW and stem water-soluble carbohydrates, as well as lower PH, thus the
two haplotypes were considered as elite haplotypes. Geographic distribution and
allelic frequencies indicated that the two preferred haplotypes Hap-1A-1 and Hap
1B-1 were positively selected in the process of Chinese wheat breeding. These
results could be valuable for genetic improvement and germplasm enhancement using
molecular marker assisted selection in wheat breeding.
PMID- 28400775
TI - In silico MCMV Silencing Concludes Potential Host-Derived miRNAs in Maize.
AB - Maize Chlorotic Mottle Virus (MCMV) is a deleterious pathogen which causes Maize
Lethal Necrosis Disease (MLND) that results in substantial yield loss of Maize
crop worldwide. The positive-sense RNA genome of MCMV (4.4 kb) encodes six
proteins: P32 (32 kDa protein), RNA dependent RNA polymerases (P50 and P111), P31
(31 kDa protein), P7 (7 kDa protein), coat protein (25 kDa). P31, P7 and coat
protein are encoded from sgRNA1, located at the 3'end of the genome and sgRNA2 is
located at the extremity of the 3'genome end. The objective of this study is to
locate the possible attachment sites of Zea mays derived miRNAs in the genome of
MCMV using four diverse miRNA target prediction algorithms. In total, 321 mature
miRNAs were retrieved from miRBase (miRNA database) and were tested for
hybridization of MCMV genome. These algorithms considered the parameters of seed
pairing, minimum free energy, target site accessibility, multiple target sites,
pattern recognition and folding energy for attachment. Out of 321 miRNAs only 10
maize miRNAs are predicted for silencing of MCMV genome. The results of this
study can hence act as the first step towards the development of MCMV resistant
transgenic Maize plants through expression of the selected miRNAs.
PMID- 28400776
TI - Translation and Co-translational Membrane Engagement of Plastid-encoded
Chlorophyll-binding Proteins Are Not Influenced by Chlorophyll Availability in
Maize.
AB - Chlorophyll is an indispensable constituent of the photosynthetic machinery in
green organisms. Bound by apoproteins of photosystems I and II, chlorophyll
performs light-harvesting and charge separation. Due to the phototoxic nature of
free chlorophyll and its precursors, chlorophyll synthesis is regulated to comply
with the availability of nascent chlorophyll-binding apoproteins. Conversely, the
synthesis and co-translational insertion of such proteins into the thylakoid
membrane have been suggested to be influenced by chlorophyll availability. In
this study, we addressed these hypotheses by using ribosome profiling to examine
the synthesis and membrane targeting of chlorophyll-binding apoproteins in
chlorophyll-deficient chlH maize mutants (Zm-chlH). ChlH encodes the H subunit of
the magnesium chelatase (also known as GUN5), which catalyzes the first committed
step in chlorophyll synthesis. Our results show that the number and distribution
of ribosomes on plastid mRNAs encoding chlorophyll-binding apoproteins are not
substantially altered in Zm-chlH mutants, suggesting that chlorophyll has no
impact on ribosome dynamics. Additionally, a Zm-chlH mutation does not change the
amino acid position at which nascent chlorophyll-binding apoproteins engage the
thylakoid membrane, nor the efficiency with which membrane-engagement occurs.
Together, these results provide evidence that chlorophyll availability does not
selectively activate the translation of plastid mRNAs encoding chlorophyll
apoproteins. Our results imply that co- or post-translational proteolysis of
apoproteins is the primary mechanism that adjusts apoprotein abundance to
chlorophyll availability in plants.
PMID- 28400777
TI - Quantitative Methods to Assess Differential Susceptibility of Arabidopsis
thaliana Natural Accessions to Dickeya dadantii.
AB - Among the most devastating bacterial diseases of plants, soft rot provoked by
Dickeya spp. cause crop yield losses on a large range of species with potato
being the most economically important. The use of antibiotics being prohibited in
most countries in the field, identifying tolerance genes is expected to be one of
the most effective alternate disease control approaches. A prerequisite for the
identification of tolerance genes is to develop robust disease quantification
methods and to identify tolerant plant genotypes. In this work, we investigate
the feasibility of the exploitation of Arabidopsis thaliana natural variation to
find tolerant genotypes and to develop robust quantification methods. We compared
different quantification methods that score either symptom development or
bacterial populations in planta. An easy to set up and reliable bacterial
quantification method based on qPCR amplification of bacterial DNA was validated.
This study demonstrates that it is possible to conduct a robust phenotyping of
soft rot disease, and that Arabidopsis natural accessions are a relevant source
of tolerance genes.
PMID- 28400778
TI - Verticillium dahliae's Isochorismatase Hydrolase Is a Virulence Factor That
Contributes to Interference With Potato's Salicylate and Jasmonate Defense
Signaling.
AB - This study aimed to dissect the function of the Isochorismatase Hydrolase (ICSH1)
gene in Verticillium dahliae's pathogenesis on potato. VdICSH1 was up-regulated
in V. dahliae after induction with extracts from potato tissues. Its expression
increased more in response to root extracts than to leaf and stem extracts.
However, such expression in response to root extracts was not significantly
different in the highly and weakly aggressive isolates tested. During infection
of detached potato leaves, VdICSH1 expression increased significantly in the
highly aggressive isolate compared to the weakly aggressive one. We generated
icsh1 mutants from a highly aggressive isolate of V. dahliae and compared their
pathogenicity with that of the original wild type strain. The analysis showed
that this gene is required for full virulence of V. dahliae on potatoes. When we
previously found differential accumulation of ICSH1 protein in favor of the
highly aggressive isolate, as opposed to the weakly aggressive one, we had
hypothesized that ICSH would interfere with the host's defense SA-based
signaling. Here, we measured the accumulation of both salicylic acid (SA) and
jasmonic acid (JA) in potato plants inoculated with an icsh1 mutant in comparison
with the wild type strain. The higher accumulation of bound SA in the leaves in
response to the icsh1 mutant compared to the wild type confirms the hypothesis
that ICSH1 interferes with SA. However, the different trends in SA and JA
accumulation in potato in the roots and in the stems at the early infection
stages compared to the leaves at later stages indicate that they are both
associated to potato defenses against V. dahliae. The expression of members of
the isochorismatase family in the icsh1 mutants compensate that of ICSH1
transcripts, but this compensation disappears in presence of the potato leaf
extracts. This study indicates ICSH1's involvement in V. dahliae's pathogenicity
and provides more insight into its alteration of the SA/JA defense signaling's
networking.
PMID- 28400780
TI - Overexpression of a New Osmotin-Like Protein Gene (SindOLP) Confers Tolerance
against Biotic and Abiotic Stresses in Sesame.
AB - Osmotin-like proteins (OLPs), of PR-5 family, mediate defense against abiotic,
and biotic stresses in plants. Overexpression in sesame of an OLP gene (SindOLP),
enhanced tolerance against drought, salinity, oxidative stress, and the charcoal
rot pathogen. SindOLP was expressed in all parts and localized to the cytosol.
The transgenic plants recovered after prolonged drought and salinity stress,
showing less electrolyte leakage, more water content, longer roots, and smaller
stomatal aperture compared to control plants. There was an increase in osmolytes,
ROS-scavenging enzymes, chlorophyll content, proline, secondary metabolites, and
reduced lipid peroxidation in the transgenic sesame under multiple stresses. The
OLP gene imparted increased tolerance through the increased expression of three
genes coding for ROS scavenging enzymes and five defense-related marker genes
functioning in the JA/ET and SA pathways, namely Si-Apetala2, Si-Ethylene
responsive factor, Si-Defensin, Si-Chitinase, and Si-Thaumatin-like protein were
monitored. The transgenic lines showed greater survival under different stresses
compared to control through the integrated activation of multiple components of
the defense signaling cascade. This is the first report of transgenic sesame and
first of any study done on defense-related genes in sesame. This is also the
first attempt at understanding the molecular mechanism underlying multi-stress
tolerance imparted by an OLP.
PMID- 28400779
TI - Making Plants Break a Sweat: the Structure, Function, and Evolution of Plant Salt
Glands.
AB - Salt stress is a complex trait that poses a grand challenge in developing new
crops better adapted to saline environments. Some plants, called
recretohalophytes, that have naturally evolved to secrete excess salts through
salt glands, offer an underexplored genetic resource for examining how plant
development, anatomy, and physiology integrate to prevent excess salt from
building up to toxic levels in plant tissue. In this review we examine the
structure and evolution of salt glands, salt gland-specific gene expression, and
the possibility that all salt glands have originated via evolutionary
modifications of trichomes. Salt secretion via salt glands is found in more than
50 species in 14 angiosperm families distributed in caryophyllales, asterids,
rosids, and grasses. The salt glands of these distantly related clades can be
grouped into four structural classes. Although salt glands appear to have
originated independently at least 12 times, they share convergently evolved
features that facilitate salt compartmentalization and excretion. We review the
structural diversity and evolution of salt glands, major transporters and
proteins associated with salt transport and secretion in halophytes, salt gland
relevant gene expression regulation, and the prospect for using new genomic and
transcriptomic tools in combination with information from model organisms to
better understand how salt glands contribute to salt tolerance. Finally, we
consider the prospects for using this knowledge to engineer salt glands to
increase salt tolerance in model species, and ultimately in crops.
PMID- 28400781
TI - Seed-Derived Ethylene Facilitates Colonization but Not Aflatoxin Production by
Aspergillus flavus in Maize.
AB - Ethylene (ET) emitted by plant tissues has been broadly reported to play
important roles in plant development, response to environmental stresses and
defense against certain pathogens. Recent evidence obtained from using in vitro
fungal cultures exposed to ET suggested that exogenous ET may regulate the
production of aflatoxin by Aspergilli. However, the function of endogenous, seed
derived ET has not been explored. In this study, we found that the maize
lipoxygenase lox3 mutant, previously reported to be susceptible to Aspergillus
spp., emitted greater levels of ET upon A. flavus infection, suggesting the
potential involvement of endogenous ET in the susceptibility of maize to A.
flavus. Supporting this idea, both colonization and conidiation of A. flavus were
reduced in wild-type (WT) kernels treated with AgNO3, an ET synthesis inhibitor.
There was no ET emission from non-viable kernels colonized by A. flavus,
suggesting that living seed but not the fungus itself was the primary source of
ET released upon infection with A. flavus. The kernels of acs2 and acs6, two ET
biosynthetic mutants carrying Mutator transposons in the ACC synthase genes, ACS2
and ACS6, respectively, displayed enhanced seed colonization and conidiation, but
not the levels of aflatoxin, upon infection with A. flavus. Surprisingly, both
acs2 and acs6 mutant kernels emitted greater levels of ET in response to
infection by A. flavus as compared with WT seed. The increased ET in single
mutants was found to be due to overexpression of functional ACS genes in response
to A. flavus infection. Collectively, these findings suggested that ET emitted by
infected seed facilitates colonization by A. flavus but not aflatoxin production.
PMID- 28400782
TI - Genomic and Phenomic Screens for Flower Related RING Type Ubiquitin E3 Ligases in
Arabidopsis.
AB - Flowering time control integrates endogenous as well as environmental signals to
promote flower development. The pathways and molecular networks involved are
complex and integrate many modes of signal transduction. In plants ubiquitin
mediated protein degradation pathway has been proposed to be as important mode of
signaling as phosphorylation and transcription. To systematically study the role
of ubiquitin signaling in the molecular regulation of flowering we have taken a
genomic approach to identify flower related Ubiquitin Proteasome System
components. As a large and versatile gene family the RING type ubiquitin E3
ligases were chosen as targets of the genomic screen. The complete list of
Arabidopsis RING E3 ligases were retrieved and verified in the Arabidopsis genome
v11 and their differential expression was used for their categorization into
flower organs or developmental stages. Known regulators of flowering time or
floral organ development were identified in these categories through literature
search and representative mutants for each category were purchased for functional
characterization by growth and morphological phenotyping. To this end, a workflow
was developed for high throughput phenotypic screening of growth, morphology and
flowering of nearly a thousand Arabidopsis plants in one experimental round.
PMID- 28400783
TI - Genetic Diversity under Soil Compaction in Wheat: Root Number as a Promising
Trait for Early Plant Vigor.
AB - Soil compaction of arable land, caused by heavy machinery constitutes a major
threat to agricultural soils in industrialized countries. The degradation of soil
structure due to compaction leads to decreased (macro-) porosity resulting in
increased mechanical impedance, which adversely affects root growth and crop
productivity. New crop cultivars, with root systems that are adapted to
conditions of increased soil strength, are needed to overcome the limiting
effects of soil compaction on plant growth. This study aimed (i) to quantify the
genetic diversity of early root system development in wheat and to relate this to
shoot development under different soil bulk densities and (ii) to test whether
root numbers are suitable traits to assess the genotypic tolerance to soil
compaction. Fourteen wheat genotypes were grown for 3 weeks in a growth chamber
under low (1.3 g cm-3), moderate (1.45 g cm-3), and high soil bulk density (1.6 g
cm-3). Using X-ray computed tomography root system development was quantified in
weekly intervals, which was complemented by weekly measurements of plant height.
The development of the root system, quantified via the number of axial and
lateral roots was strongly correlated (0.78 < r < 0.88, p < 0.01) to the
development of plant height. Furthermore, significant effects (p < 0.01) of the
genotype on root system development and plant vigor traits were observed. Under
moderate soil strength final axial and lateral root numbers were significantly
correlated (0.57 < r < 0.84, p < 0.05) to shoot dry weight. Furthermore, broad
sense heritability of axial and lateral root number was higher than 50% and
comparable to values calculated for shoot traits. Our results showed that there
is genetic diversity in wheat with respect to root system responses to increased
soil strength and that root numbers are suitable indicators to explain the
responses and the tolerance to such conditions. Since root numbers are heritable
and can be assessed at high throughput rates under laboratory and field
conditions, root number is considered a promising trait for screening toward
compaction tolerant varieties.
PMID- 28400784
TI - High-Throughput Phenotyping of Sorghum Plant Height Using an Unmanned Aerial
Vehicle and Its Application to Genomic Prediction Modeling.
AB - Genomics-assisted breeding methods have been rapidly developed with novel
technologies such as next-generation sequencing, genomic selection and genome
wide association study. However, phenotyping is still time consuming and is a
serious bottleneck in genomics-assisted breeding. In this study, we established a
high-throughput phenotyping system for sorghum plant height and its response to
nitrogen availability; this system relies on the use of unmanned aerial vehicle
(UAV) remote sensing with either an RGB or near-infrared, green and blue (NIR-GB)
camera. We evaluated the potential of remote sensing to provide phenotype
training data in a genomic prediction model. UAV remote sensing with the NIR-GB
camera and the 50th percentile of digital surface model, which is an indicator of
height, performed well. The correlation coefficient between plant height measured
by UAV remote sensing (PHUAV) and plant height measured with a ruler (PHR) was
0.523. Because PHUAV was overestimated (probably because of the presence of
taller plants on adjacent plots), the correlation coefficient between PHUAV and
PHR was increased to 0.678 by using one of the two replications (that with the
lower PHUAV value). Genomic prediction modeling performed well under the low
fertilization condition, probably because PHUAV overestimation was smaller under
this condition due to a lower plant height. The predicted values of PHUAV and PHR
were highly correlated with each other (r = 0.842). This result suggests that the
genomic prediction models generated with PHUAV were almost identical and that the
performance of UAV remote sensing was similar to that of traditional measurements
in genomic prediction modeling. UAV remote sensing has a high potential to
increase the throughput of phenotyping and decrease its cost. UAV remote sensing
will be an important and indispensable tool for high-throughput genomics-assisted
plant breeding.
PMID- 28400785
TI - Dihydroflavonol 4-Reductase Genes from Freesia hybrida Play Important and
Partially Overlapping Roles in the Biosynthesis of Flavonoids.
AB - Dihydroflavonol-4-reductase (DFR) is a key enzyme in the reduction of
dihydroflavonols to leucoanthocyanidins in both anthocyanin biosynthesis and
proanthocyanidin accumulation. In many plant species, it is encoded by a gene
family, however, how the different copies evolve either to function in different
tissues or at different times or to specialize in the use of different but
related substrates needs to be further investigated, especially in monocot
plants. In this study, a total of eight putative DFR-like genes were firstly
cloned from Freesia hybrida. Phylogenetic analysis showed that they were
classified into different branches, and FhDFR1, FhDFR2, and FhDFR3 were clustered
into DFR subgroup, whereas others fell into the group with cinnamoyl-CoA
reductase (CCR) proteins. Then, the functions of the three FhDFR genes were
further characterized. Different spatio-temporal transcription patterns and
levels were observed, indicating that the duplicated FhDFR genes might function
divergently. After introducing them into Arabidopsis dfr (tt3-1) mutant plants,
partial complementation of the loss of cyanidin derivative synthesis was
observed, implying that FhDFRs could convert dihydroquercetin to leucocyanidin in
planta. Biochemical assays also showed that FhDFR1, FhDFR2, and FhDFR3 could
utilize dihydromyricetin to generate leucodelphinidin, while FhDFR2 could also
catalyze the formation of leucocyanidin from dihydrocyanidin. On the contrary,
neither transgenic nor biochemical analysis demonstrated that FhDFR proteins
could reduce dihydrokaempferol to leucopelargonidin. These results were
consistent with the freesia flower anthocyanin profiles, among which delphinidin
derivatives were predominant, with minor quantities of cyanidin derivatives and
undetectable pelargonidin derivatives. Thus, it can be deduced that substrate
specificities of DFRs were the determinant for the categories of anthocyanins
aglycons accumulated in F. hybrida. Furthermore, we also found that the
divergence of the expression patterns for FhDFR genes might be controlled at
transcriptional level, as the expression of FhDFR1/FhDFR2 and FhDFR3 was
controlled by a potential MBW regulatory complex with different activation
efficiencies. Therefore, it can be concluded that the DFR-like genes from F.
hybrida have diverged during evolution to play partially overlapping roles in the
flavonoid biosynthesis, and the results will contribute to the study of evolution
of DFR gene families in angiosperms, especially for monocot plants.
PMID- 28400786
TI - Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice
and Xanthomonas oryzae.
AB - Plants are constantly challenged by a wide range of pathogens and have therefore
evolved an array of mechanisms to defend against them. In response to these
defense systems, pathogens have evolved strategies to avoid recognition and
suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing
with the resistance of rice to Xanthomonas oryzae have added a new twist to our
understanding of this fascinating co-evolutionary arms race (Ji et al., 2016;
Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop
sophisticated effector mimics to trick recognition.
PMID- 28400787
TI - Silicification in Grasses: Variation between Different Cell Types.
AB - Plants take up silicon as mono-silicic acid, which is released to soil by the
weathering of silicate minerals. Silicic acid can be taken up by plant roots
passively or actively, and later it is deposited in its polymerized form as
amorphous hydrated silica. Major silica depositions in grasses occur in root
endodermis, leaf epidermal cells, and outer epidermal cells of inflorescence
bracts. Debates are rife about the mechanism of silica deposition, and two
contrasting scenarios are often proposed to explain it. According to the passive
mode of silicification, silica deposition is a result of silicic acid
condensation due to dehydration, such as during transpirational loss of water
from the aboveground organs. In general, silicification and transpiration are
positively correlated, and continued silicification is sometimes observed after
cell and tissue maturity. The other mode of silicification proposes the
involvement of some biological factors, and is based on observations that
silicification is not necessarily coupled with transpiration. Here, we review
evidence for both mechanisms of silicification, and propose that the deposition
mechanism is specific to the cell type. Considering all the cell types together,
our conclusion is that grass silica deposition can be divided into three modes:
spontaneous cell wall silicification, directed cell wall silicification, and
directed paramural silicification in silica cells.
PMID- 28400790
TI - Current view and perspectives in amyotrophic lateral sclerosis.
AB - Amyotrophic lateral sclerosis (ALS), identified as a distinct clinical entity by
Charcot since the end of the nineteenth century, is a devastating and fatal
neurodegenerative disorder that affects motor neurons in the brain, brainstem and
spinal cord. Survival of patients with ALS is associated with several factors
such as clinical phenotype, age at onset, gender, early presence of respiratory
failure, weight loss and treatment with Riluzole (the only disease-modifying drug
approved for this disease). Nowadays, there is still no curative treatment for
ALS: palliative care and symptomatic treatment are therefore essential components
in the management of these patients. Nevertheless, the scientific knowledge in
the field of ALS motor neuron degeneration is growing, with the prospect of new
treatments. Based on this physiopathological knowledge, several new therapeutic
targets are being studied, involving various mechanisms such as excitotoxicity,
neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism
and other attractive concepts. Moreover, it is also important to identify
reliable biomarkers that will be essential components for future therapeutic
development and study design in ALS. In this review, we present the main recent
advances and promising therapeutics and biomarkers in the field of ALS.
PMID- 28400788
TI - The LIN28/let-7 Pathway in Cancer.
AB - Among all tumor suppressor microRNAs, reduced let-7 expression occurs most
frequently in cancer and typically correlates with poor prognosis. Activation of
either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto
oncogenes, is responsible for the global post-transcriptional downregulation of
the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds
the terminal loop of precursor let-7 and recruits the Terminal Uridylyl
Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking
microRNA biogenesis and tumor suppressor function. For LIN28B, the precise
mechanism responsible for let-7 inhibition remains controversial. Functionally,
the decrease in let-7 microRNAs leads to overexpression of their oncogenic
targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models
demonstrate that ectopic LIN28 expression is sufficient to drive and/or
accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the
LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer
stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation
and several chemotherapies. Also, emerging evidence will be presented suggesting
that molecular targeting of this pathway may provide therapeutic benefit in
cancer.
PMID- 28400789
TI - The promise of stem cell-based therapeutics in ophthalmology.
AB - The promising role of cellular therapies in the preservation and restoration of
visual function has prompted intensive efforts to characterize embryonic, adult,
and induced pluripotent stem cells for regenerative purposes. Three main
approaches to the use of stem cells have been described: sustained drug delivery,
immunomodulation, and differentiation into various ocular structures. Studies of
the differentiation capacity of all three types of stem cells into epithelial,
neural, glial and vascular phenotypes have reached proof-of-concept in culture,
but the correction of vision is still in the early developmental stages, and the
requirements for effective in vivo implementation are still unclear. We present
an overview of some of the preclinical findings on stem-cell rescue and
regeneration of the cornea and retina in acute injury and degenerative disorders.
PMID- 28400791
TI - Axonal remodeling in the corticospinal tract after stroke: how does
rehabilitative training modulate it?
AB - Stroke causes long-term disability, and rehabilitative training is commonly used
to improve the consecutive functional recovery. Following brain damage, surviving
neurons undergo morphological alterations to reconstruct the remaining neural
network. In the motor system, such neural network remodeling is observed as a
motor map reorganization. Because of its significant correlation with functional
recovery, motor map reorganization has been regarded as a key phenomenon for
functional recovery after stroke. Although the mechanism underlying motor map
reorganization remains unclear, increasing evidence has shown a critical role for
axonal remodeling in the corticospinal tract. In this study, we review previous
studies investigating axonal remodeling in the corticospinal tract after stroke
and discuss which mechanisms may underlie the stimulatory effect of
rehabilitative training. Axonal remodeling in the corticospinal tract can be
classified into three types based on the location and the original targets of
corticospinal neurons, and it seems that all the surviving corticospinal neurons
in both ipsilesional and contralesional hemisphere can participate in axonal
remodeling and motor map reorganization. Through axonal remodeling, corticospinal
neurons alter their output selectivity from a single to multiple areas to
compensate for the lost function. The remodeling of the corticospinal axon is
influenced by the extent of tissue destruction and promoted by various
therapeutic interventions, including rehabilitative training. Although the
precise molecular mechanism underlying rehabilitation-promoted axonal remodeling
remains elusive, previous data suggest that rehabilitative training promotes
axonal remodeling by upregulating growth-promoting and downregulating growth
inhibiting signals.
PMID- 28400792
TI - Toll-like receptor 4 as a possible therapeutic target for delayed brain injuries
after aneurysmal subarachnoid hemorrhage.
AB - Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage
(SAH), and Toll-like receptor (TLR) 4 may be an important therapeutic target for
post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in
various cell types in the central nervous system, and is unique in that it can
signal through both the myeloid differentiation primary-response protein 88
dependent and the toll receptor associated activator of interferon-dependent
cascades to coordinate the maximal inflammatory response. TLR4 can be activated
by many endogenous ligands having damage-associated molecular patterns including
heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant
inflammatory reaction and thereby tissue damages may furthermore activate TLR4.
It is widely accepted that the excreted products of TLR4 signaling alter neuronal
functions. Previous studies have focused on the pathway through nuclear factor
(NF)-kappaB signaling among TLR4 signaling pathways as to the development of
early brain injury (EBI) such as neuronal apoptosis and blood-brain barrier
disruption, and cerebral vasospasm. However, many findings suggest that both
pathways via NF-kappaB and mitogen-activated protein kinases may be involved in
EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is
important to improve outcomes after SAH, because both EBI and vasopasm are
responsible for delayed brain injuries or delayed cerebral ischemia, the most
important preventable cause of poor outcomes after SAH. Increasing evidence has
shown that TLR4 signaling plays an important role in SAH-induced brain injuries.
Better understanding of the roles of TLR4 signaling in SAH will facilitate
development of new treatments.
PMID- 28400793
TI - The exciting potential of nanotherapy in brain-tumor targeted drug delivery
approaches.
AB - Delivering therapeutics to the central nervous system (CNS) and brain-tumor has
been a major challenge. The current standard treatment approaches for the brain
tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and
chemotherapy. However, the current treatments are limited in providing
significant benefits to the patients and despite recent technological
advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is
limited by the lack of effective and targeted strategies to deliver
chemotherapeutic agents across the blood-brain barrier (BBB). The BBB is the main
obstacle that must be overcome to allow compounds to reach their targets in the
brain. Recent advances have boosted the nanotherapeutic approaches in providing
an attractive strategy in improving the drug delivery across the BBB and into the
CNS. Compared to conventional formulations, nanoformulations offer significant
advantages in CNS drug delivery approaches. Considering the above facts, in this
review, the physiological/anatomical features of the brain-tumor and the BBB are
briefly discussed. The drug transport mechanisms at the BBB are outlined. The
approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor
using nanocarriers are summarized. In addition, the challenges that need to be
addressed in nanotherapeutic approaches for their enhanced clinical application
in brain-tumor therapy are discussed.
PMID- 28400794
TI - Intracellular compartmentation of cAMP promotes neuroprotection and regeneration
of CNS neurons.
PMID- 28400795
TI - Astrogenesis versus astrogliosis.
PMID- 28400796
TI - Curcumin-primed and curcumin-loaded exosomes: potential neural therapy.
PMID- 28400797
TI - Targeting amyloid precursor protein shuttling and processing - long before
amyloid beta formation.
PMID- 28400798
TI - Neuroprotective properties of dietary saffron: more than just a chemical
scavenger?
PMID- 28400799
TI - Targeting the guanine-based purinergic system in Alzheimer's disease.
PMID- 28400800
TI - Mitochondria in the context of Parkinson's disease.
PMID- 28400801
TI - Neonatal seizures and disruption to neurotransmitter systems.
PMID- 28400802
TI - PDE5 inhibitors promote recovery of peripheral neuropathy in diabetic mice.
PMID- 28400803
TI - Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from
transient cerebral ischemic injury by increasing the expression of antioxidant
enzymes.
AB - Quercetin (QE; 3,5,7,3',4'-pentahydroxyflavone), a well-known flavonoid, has been
shown to prevent against neurodegenerative disorders and ischemic insults.
However, few studies are reported regarding the neuroprotective mechanisms of QE
after ischemic insults. Therefore, in this study, we investigated the effects of
QE on ischemic injury and the expression of antioxidant enzymes in the
hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral
ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment
with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which
was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B
histofluorescence staining. In addition, pretreatment with QE significantly
increased the expression levels of endogenous antioxidant enzymes Cu/Zn
superoxide dismutase, Mn superoxide dismutase, catalase and glutathione
peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic
injury. These findings demonstrate that pretreated QE displayed strong
neuroprotective effects against transient cerebral ischemia by increasing the
expression of antioxidant enzymes.
PMID- 28400804
TI - Electroacupuncture-induced neuroprotection against focal cerebral ischemia in the
rat is mediated by adenosine A1 receptors.
AB - The activation of adenosine A1 receptors is important for protecting against
ischemic brain injury and pretreatment with electroacupuncture has been shown to
mitigate ischemic brain insult. The aim of this study was to test whether the
adenosine A1 receptor mediates electroacupuncture pretreatment-induced
neuroprotection against ischemic brain injury. We first performed 30 minutes of
electroacupuncture pretreatment at the Baihui acupoint (GV20), delivered with a
current of 1 mA, a frequency of 2/15 Hz, and a depth of 1 mm. High-performance
liquid chromatography found that adenosine triphosphate and adenosine levels
peaked in the cerebral cortex at 15 minutes and 120 minutes after
electroacupuncture pretreatment, respectively. We further examined the effect of
15 or 120 minutes electroacupuncture treatment on ischemic brain injury in a rat
middle cerebral artery-occlusion model. We found that at 24 hours reperfusion,120
minutes after electroacupuncture pretreatment, but not for 15 minutes,
significantly reduced behavioral deficits and infarct volumes. Last, we
demonstrated that the protective effect gained by 120 minutes after
electroacupuncture treatment before ischemic injury was abolished by pretreatment
with the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 mg/kg,
intraperitoneally). Our results suggest that pretreatment with electroacupuncture
at the Baihui acupoint elicits protection against transient cerebral ischemia via
action at adenosine A1 receptors.
PMID- 28400805
TI - 3'-Daidzein sulfonate sodium improves mitochondrial functions after cerebral
ischemia/reperfusion injury.
AB - 3'-Daidzein sulfonate sodium is a new synthetic water-soluble compound derived
from daidzein (an active ingredient of the kudzu vine root). It has been shown to
have a protective effect on cerebral ischemia/reperfusion injury in rats. We plan
to study the mechanism of its protective effect. 3'-Daidzein sulfonate sodium was
injected in rats after cerebral ischemia/reperfusion injury. Results showed that
3'-daidzein sulfonate sodium significantly reduced mitochondrial swelling,
significantly elevated the mitochondrial membrane potential, increased
mitochondrial superoxide dismutase and glutathione peroxidase activities, and
decreased mitochondrial malondialdehyde levels. 3'-Daidzein sulfonate sodium
improved the structural integrity of the blood-brain barrier and reduced blood
brain barrier permeability. These findings confirmed that 3'-daidzein sulfonate
sodium has a protective effect on mitochondrial functions after cerebral
ischemia/reperfusion injury, improves brain energy metabolism, and provides
protection against blood-brain barrier damage.
PMID- 28400806
TI - A protease-activated receptor 1 antagonist protects against global cerebral
ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits.
AB - Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which
causes brain damage through protease-activated receptor 1 (PAR1). However, the
role and mechanisms underlying the effects of PAR1 activation require further
elucidation. Therefore, the present study investigated the effects of the PAR1
antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by
cardiac arrest. SCH79797 was intravenously administered 10 minutes after the
model was established. Forty-eight hours later, compared with those administered
saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as
assessed by serum neuron specific enolase levels and less neurological
dysfunction as determined using cerebral performance category scores.
Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell
infiltration, and c-Jun levels were decreased, whereas extracellular signal
regulated kinase phosphorylation levels were increased. All of these changes were
inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt
pathway inhibitor LY29004 (3 mg/kg) 10 minutes before the SCH79797 intervention.
These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory
and anti-apoptotic effects, possibly by modulating the extracellular signal
regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt
pathways.
PMID- 28400807
TI - Modulatory effects of acupuncture on brain networks in mild cognitive impairment
patients.
AB - Functional magnetic resonance imaging has been widely used to investigate the
effects of acupuncture on neural activity. However, most functional magnetic
resonance imaging studies have focused on acute changes in brain activation
induced by acupuncture. Thus, the time course of the therapeutic effects of
acupuncture remains unclear. In this study, 32 patients with amnestic mild
cognitive impairment were randomly divided into two groups, where they received
either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were
either twirled at Tiaoshen Yizhi acupoints, including Sishencong (EX-HN1),
Yintang (EX-HN3), Neiguan (PC6), Taixi (KI3), Fenglong (ST40), and Taichong
(LR3), or at related sham acupoints at a depth of approximately 15 mm, an angle
of +/- 60 degrees , and a rate of approximately 120 times per minute. Acupuncture
was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting
state functional magnetic resonance imaging indicated that connections between
cognition-related regions such as the insula, dorsolateral prefrontal cortex,
hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex
increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral
prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the
Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture.
In the sham acupoint acupuncture group, connections between brain regions were
dispersed, and we found no differences in cognitive function following the
treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints
can regulate brain networks by increasing connectivity between cognition-related
regions, thereby improving cognitive function in patients with mild cognitive
impairment.
PMID- 28400808
TI - DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese
Uyghur children.
AB - Developmental dyslexia is a complex reading and writing disorder with strong
genetic components. In previous genetic studies about dyslexia, a number of
candidate genes have been identified. These include DCDC2, which has repeatedly
been associated with developmental dyslexia in various European and American
populations. However, data regarding this relationship are varied according to
population. The Uyghur people of China represent a Eurasian population with an
interesting genetic profile. Thus, this group may provide useful information
about the association between DCDC2 gene polymorphisms and dyslexia. In the
current study, we examined genetic data from 392 Uyghur children aged 8-12 years
old from the Xinjiang Uyghur Autonomous Region of China. Participants included
196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA
was isolated from oral mucosal cell samples and fourteen single nucleotide
polymorphisms (rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619,
rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and
rs1087266) in DCDC2 were screened via the SNPscan method. We compared SNP
frequencies in five models (Codominant, Dominant, Recessive, Heterozygote
advantage, and Allele) between the two groups by means of the chi-squared test. A
single-locus analysis indicated that, with regard to the allele frequency of
these polymorphisms, three SNPs (rs807724, rs2274305, and rs4599626) were
associated with dyslexia. rs9467075 and rs2274305 displayed significant
associations with developmental dyslexia under the dominant model. rs6456593 and
rs6922023 were significantly associated with developmental dyslexia under the
dominant model and in the heterozygous genotype. Additionally, we discovered that
the T-G-C-T of the four-marker haplotype (rs9295619-rs807701-rs807724-rs2274305)
and the T-A of the two-marker haplotype (rs3765502-1087266) were significantly
different between cases and controls. Thus, we conclude that DCDC2 gene
polymorphisms are associated with developmental dyslexia in Chinese Uyghur
children.
PMID- 28400809
TI - Correction: Future directions for using estrogen receptor agonists in the
treatment of acute and chronic spinal cord injury.
AB - [This corrects the article on p. 1418 in vol. 11, PMID: 27857741.].
PMID- 28400810
TI - Tanshinone IIA improves functional recovery in spinal cord injury-induced lower
urinary tract dysfunction.
AB - Tanshinone IIA, extracted from Salvia miltiorrhiza Bunge, exerts neuroprotective
effects through its anti-inflammatory, anti-oxidative and anti-apoptotic
properties. This study intravenously injected tanshinone IIA 20 mg/kg into rat
models of spinal cord injury for 7 consecutive days. Results showed that
tanshinone IIA could reduce the inflammation, edema as well as compensatory
thickening of the bladder tissue, improve urodynamic parameters, attenuate
secondary injury, and promote spinal cord regeneration. The number of
hypertrophic and apoptotic dorsal root ganglion (L6-S1) cells was less after
treatment with tanshinone IIA. The effects of tanshinone IIA were similar to
intravenous injection of 30 mg/kg methylprednisolone. These findings suggested
that tanshinone IIA improved functional recovery after spinal cord injury-induced
lower urinary tract dysfunction by remodeling the spinal pathway involved in
lower urinary tract control.
PMID- 28400811
TI - Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho
associated kinase II in spinal cord injury rats.
AB - Electroacupuncture is beneficial for the recovery of spinal cord injury, but the
underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK) signaling
pathway regulates the actin cytoskeleton by controlling the adhesive and
migratory behaviors of cells that could inhibit neurite regrowth after neural
injury and consequently hinder the recovery from spinal cord injury. Therefore,
we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to
promote the recovery of spinal cord injury. In our experiments, the spinal cord
injury in adult Sprague-Dawley rats was caused by an impact device. Those rats
were subjected to electroacupuncture at Yaoyangguan (GV3), Dazhui (GV14), Zusanli
(ST36) and Ciliao (BL32) and/or monosialoganglioside treatment. Behavioral scores
revealed that the hindlimb motor functions improved with those treatments. Real
time quantitative polymerase chain reaction, fluorescence in situ hybridization
and western blot assay showed that electroacupuncture suppressed the mRNA and
protein expression of Rho-A and Rho-associated kinase II (ROCKII) of injured
spinal cord. Although monosialoganglioside promoted the recovery of hindlimb
motor function, monosialoganglioside did not affect the expression of Rho-A and
ROCKII. However, electroacupuncture combined with monosialoganglioside did not
further improve the motor function or suppress the expression of Rho-A and
ROCKII. Our data suggested that the electroacupuncture could specifically inhibit
the activation of the Rho/ROCK signaling pathway thus partially contributing to
the repair of injured spinal cord. Monosialoganglioside could promote the motor
function but did not suppress expression of RhoA and ROCKII. There was no
synergistic effect of electroacupuncture combined with monosialoganglioside.
PMID- 28400812
TI - Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced
apoptosis in spinal cord astrocytes by inhibiting integrated stress response.
AB - We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R)
induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the
integrated stress response, which involves protein kinase R-like endoplasmic
reticulum kinase (PERK), eukaryotic initiation factor 2-alpha (eIF2alpha) and
activating transcription factor 4 (ATF4). We hypothesized that edaravone, a low
molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced
apoptosis of spinal cord astrocytes. To test this, we established primary
cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or
without edaravone (0.1, 1, 10, 100 MUM) treatment. We found that 100 MUM of
edaravone significantly suppressed astrocyte apoptosis and inhibited the release
of reactive oxygen species. It also inhibited the activation of caspase-12 and
caspase-3, and reduced the expression of homologous CCAAT/enhancer binding
protein, phosphorylated (p)-PERK, p-eIF2alpha, and ATF4. These results point to a
new use of an established drug in the prevention of OGSD/R-mediated spinal cord
astrocyte apoptosis via the integrated stress response.
PMID- 28400813
TI - Adenyl cyclase activator forskolin protects against Huntington's disease-like
neurodegenerative disorders.
AB - Long term suppression of succinate dehydrogenase by selective inhibitor 3
nitropropionic acid has been used in rodents to model Huntington's disease where
mitochondrial dysfunction and oxidative damages are primary pathological
hallmarks for neuronal damage. Improvements in learning and memory abilities,
recovery of energy levels, and reduction of excitotoxicity damage can be achieved
through activation of Adenyl cyclase enzyme by a specific phytochemical
forskolin. In this study, intraperitoneal administration of 10 mg/kg 3
nitropropionic acid for 15 days in rats notably reduced body weight, worsened
motor cocordination (grip strength, beam crossing task, locomotor activity),
resulted in learning and memory deficits, greatly increased acetylcholinesterase,
lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased
adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase,
and reduced glutathione levels in the striatum, cortex and hippocampus.
Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently
reversed these behavioral, biochemical and pathological changes caused by 3
nitropropionic acid. These results suggest that forskolin exhibits
neuroprotective effects on 3-nitropropionic acid-induced Huntington's disease
like neurodegeneration.
PMID- 28400814
TI - Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular
mechanism in the senescence-accelerated mouse prone 8.
AB - Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma
Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in
pure water, is neuroprotective in animal models of various cognitive disorders,
but its molecular mechanism remains unclear. We administered Tiantai No. 1
intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of
Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and
evaluated their behavior in the Morris water maze and expression of Alzheimer's
disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency
in the water maze training trials, and increased swimming time in the target
quadrant during the spatial probe test, indicating that Tiantai No. 1 improved
learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.
1 restored the proliferation potential of Ki67-positive cells in the hippocampus.
In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less
accumulation of amyloid-beta and phosphorylated tau. These results suggest that
Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease
and acts by restoring neuronal number and proliferation potential in the
hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of
amyloid-beta and phosphorylated tau.
PMID- 28400815
TI - Delayed treatment of secondary degeneration following acute optic nerve
transection using a combination of ion channel inhibitors.
AB - Studies have shown that a combined application of several ion channel inhibitors
immediately after central nervous system injury can inhibit secondary
degeneration. However, for clinical use, it is necessary to determine how long
after injury the combined treatment of several ion channel inhibitors can be
delayed and efficacy maintained. In this study, we delivered Ca2+ entry
inhibiting P2X7 receptor antagonist oxidized-ATP and AMPA receptor antagonist
YM872 to the optic nerve injury site via an iPRECIO@ pump immediately, 6 hours,
24 hours and 7 days after partial optic nerve transection surgery. In addition,
all of the ion channel inhibitor treated rats were administered with calcium
channel antagonist lomerizine hydrochloride. It is important to note that as a
result of implantation of the particular pumps required for programmable delivery
of therapeutics directly to the injury site, seromas occurred in a significant
proportion of animals, indicating infection around the pumps in these animals.
Improvements in visual function were observed only when treatment was delayed by
6 hours; phosphorylated Tau was reduced when treatment was delayed by 24 hours or
7 days. Improvements in structure of node/paranode of Ranvier and reductions in
oxidative stress indicators were also only observed when treatment was delayed
for 6 hours, 24 hours, or 7 days. Benefits of ion channel inhibitors were only
observed with time-delayed treatment, suggesting that delayed therapy of Ca2+ ion
channel inhibitors produces better neuroprotective effects on secondary
degeneration, at least in the presence of seromas.
PMID- 28400816
TI - The cortical activation pattern during bilateral arm raising movements.
AB - Bilateral arm raising movements have been used in brain rehabilitation for a long
time. However, no study has been reported on the effect of these movements on the
cerebral cortex. In this study, using functional near infrared spectroscopy
(fNIRS), we attempted to investigate cortical activation generated during
bilateral arm raising movements. Ten normal subjects were recruited for this
study. fNIRS was performed using an fNIRS system with 49 channels. Bilateral arm
raising movements were performed in sitting position at the rate of 0.5 Hz. We
measured values of oxyhemoglobin and total hemoglobin in five regions of
interest: the primary sensorimotor cortex, premotor cortex, supplementary motor
area, prefrontal cortex, and posterior parietal cortex. During performance of
bilateral arm raising movements, oxyhemoglobin and total hemoglobin values in the
primary sensorimotor cortex, premotor cortex, supplementary motor area, and
prefrontal cortex were similar, but higher in these regions than those in the
prefrontal cortex. We observed activation of the arm somatotopic areas of the
primary sensorimotor cortex and premotor cortex in both hemispheres during
bilateral arm raising movements. According to this result, bilateral arm raising
movements appeared to induce large-scale neuronal activation and therefore arm
raising movements would be good exercise for recovery of brain functions.
PMID- 28400817
TI - Nonhuman primate models of focal cerebral ischemia.
AB - Rodents have been widely used in the production of cerebral ischemia models.
However, successful therapies have been proven on experimental rodent stroke
model, and they have often failed to be effective when tested clinically.
Therefore, nonhuman primates were recommended as the ideal alternatives, owing to
their similarities with the human cerebrovascular system, brain metabolism, grey
to white matter ratio and even their rich behavioral repertoire. The present
review is a thorough summary of ten methods that establish nonhuman primate
models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced
occlusion, microvascular clip occlusion, autologous blood clot embolization,
balloon inflation, microcatheter embolization, coil embolization, surgical suture
embolization, suture, and photochemical induction methods. This review addresses
the advantages and disadvantages of each method, as well as precautions for each
model, compared nonhuman primates with rodents, different species of nonhuman
primates and different modeling methods. Finally it discusses various factors
that need to be considered when modelling and the method of evaluation after
modelling. These are critical for understanding their respective strengths and
weaknesses and underlie the selection of the optimum model.
PMID- 28400819
TI - The Role of Endoscopic Ultrasound in the Diagnosis and Management of Primary
Gastric Lymphoma.
AB - Endoscopic ultrasound (EUS) is considered a valuable diagnostic tool during the
workup of malignant gastric lesions, including primary gastric lymphomas (PGL).
Although endoscopy combined with multiple biopsies remains essential in the
establishment of PGL diagnosis, EUS utilization in locoregional disease staging
has been well documented in the literature. Data also support the possible role
of EUS in prediction of response to first-line treatment, that is, Helicobacter
pylori eradication. However, its application in the posttreatment setting remains
problematic, since concordance rates between endosonography and histology
findings during follow-up seem to vary substantially. The aim of the present
review is to summarize all available data regarding the role of EUS in the
management of PGL.
PMID- 28400818
TI - Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by
reducing oxidant stress and inflammation.
AB - Postoperative cognitive dysfunction is a crucial public health issue that has
been increasingly studied in efforts to reduce symptoms or prevent its
occurrence. However, effective advances remain lacking. Hyperbaric oxygen
preconditioning has proved to protect vital organs, such as the heart, liver, and
brain. Recently, it has been introduced and widely studied in the prevention of
postoperative cognitive dysfunction, with promising results. However, the
neuroprotective mechanisms underlying this phenomenon remain controversial. This
review summarizes and highlights the definition and application of hyperbaric
oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying
postoperative cognitive dysfunction, and the effects that hyperbaric oxygen
preconditioning has on postoperative cognitive dysfunction. Finally, we conclude
that hyperbaric oxygen preconditioning is an effective and feasible method to
prevent, alleviate, and improve postoperative cognitive dysfunction, and that its
mechanism of action is very complex, involving the stimulation of endogenous
antioxidant and anti-inflammation defense systems.
PMID- 28400820
TI - Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous
Adenocarcinoma: A Propensity Score-Matched Study.
AB - Aims. To compare the surgical and oncological outcomes of rectal mucinous
adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone.
Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients
treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and
2014 were matched using propensity score; the surgical and oncological outcomes
were compared. Results. Ninety-six patients were matched. Postoperative morbidity
was similar between groups. Sphincter preservation rate was higher in patients
receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045),
especially for tumors >= 3 cm but <=5 cm from the anal verge (75.0% versus 44.0%,
P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival
rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P =
0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were
similar. The 5-year local recurrence rate was lower in patients receiving
neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference
was observed in distant metastasis. A poor response to chemoradiation was
associated with higher local recurrence (P = 0.037). Conclusions. Compared with
surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter
preservation rate and reduce local recurrence, thus being beneficial for locally
advanced rectal mucinous adenocarcinoma patients.
PMID- 28400821
TI - The Great Impostor: Transaminitis Masking the Coinfection of Syphilis and Human
Immunodeficiency Virus.
AB - Introduction. The incidence of syphilis continues to rise in the United States
over the past 15 years. This disease process is classified into stages and may
present with a coinfection of Human Immunodeficiency Virus (HIV). Case Report. We
present a case of a 32-year-old African American male who presented with
cutaneous manifestations of secondary syphilis and transaminitis. A workup
revealed that the transaminitis was secondary to underlying syphilitic hepatitis
in the presence of HIV coinfection. The patient had a reactive rapid plasma
reagin (RPR) of 1 : 64 TU and reactive Treponema pallidum particle agglutination
assay (TPPA). Lab findings showed alkaline phosphate (ALP) of 648 unit/L,
aspartate aminotransferase (AST) of 251 unit/L, and alanine aminotransferase
(ALT) of 409 unit/L. Conclusion. Syphilitic hepatitis is a recognized entity in
the medical literature. It is a manifestation of secondary syphilis and it is
more commonly seen in coinfected patients with both syphilis and HIV. Therefore,
primary care physicians should keep infectious etiologies (e.g., syphilis and
HIV) in the differential diagnosis of patients who present with unexplained liver
dysfunction in a cholestatic pattern.
PMID- 28400822
TI - Pacemaker Placement in Patients with Stroke-Mediated Autonomic Dysregulation.
AB - Lateral medullary syndrome (LMS) is an ischemic disease of the medulla oblongata,
which involves the territory of the posterior inferior cerebellar artery. Lateral
medullary syndrome is often missed as the cause of autonomic dysregulation in
patients with recent brain stem stroke. Due to the location of the baroreceptor
regulatory center in the lateral medulla oblongata, patients with LMS
occasionally have autonomic dysregulation-associated clinical manifestations. We
report a case of LMS-associated autonomic dysregulation. The case presented as
sinus arrest and syncope, requiring permanent pacemaker placement. A dual-chamber
pacemaker was placed, after failure of conservative measures to alleviate the
patient's symptoms. Our case shows the importance of recognizing LMS as a
potential cause for life-threatening arrhythmias, heart block, and symptomatic
bradycardia. Placement of permanent pacemaker may be necessary in some patients
with LMS presenting with syncope, secondary to sinus arrest.
PMID- 28400823
TI - Development of a scoring system using a statistical model to predict cure status
in patients with cutaneous leishmaniasis.
AB - BACKGROUND: The present study was performed to develop a scoring system for
predicting cure status in patients with cutaneous leishmaniasis (CL). MATERIALS
AND METHODS: This study included 199 patients with CL from Skin Diseases and
Leishmaniasis Research Center (Isfahan, Iran). Data were collected as
longitudinal in each visit of patients. We applied ordinal logistic generalized
estimating equation regression to predict score on this correlated data. To
evaluate the fitted model, split sample validation method was applied. SPSS
software was used for data analysis. RESULTS: The regression coefficients of the
fitted model were used to calculate score for cure status. Based on split-sample
validation method, overall correct classification rate was 82%. CONCLUSION: This
study suggested a scoring system predict cure status in CL patients based on
clinical characteristics. Using this method, score for a CL patient is easily
obtained by physicians or health workers.
PMID- 28400825
TI - Association of anatomic variations with antrochoanal polyps in paranasal sinus
computed tomography scan.
AB - BACKGROUND: This study was designed to determine the prevalence of concomitant
anatomic variation of paranasal sinuses in patients with antrochoanal polyp
(ACP). MATERIALS AND METHODS: Among patients referred by their clinicians for
standard computed tomography scan of paranasal sinuses septal deviation, concha
bullosa, and retention cyst were evaluated in both patients with ACP as well as
in a control group. RESULTS: Of the 17 patients with ACP, fifteen patients
(88.2%) had septal deviation and two patients (11.8%) had concha bullosa. None of
the patients with ACP had retention cyst or hypertrophic turbinate. Of the 78
patients in control group, twenty-nine (37.2%) had septal deviation, six (7.7%)
had concha bullosa, seven (8.9%) had retention cyst, and one (1.2%) had
hypertrophic turbinate. Septal deviation in patients with ACP has higher
incidence (P < 0.001). CONCLUSION: This study showed that septal deviation is an
anatomic variation which is significantly concomitant with ACP. Larger studies
are needed to show the role of other anatomic variations in patients with ACP.
PMID- 28400824
TI - Melatonin and human mitochondrial diseases.
AB - Mitochondrial dysfunction is one of the main causative factors in a wide variety
of complications such as neurodegenerative disorders, ischemia/reperfusion, aging
process, and septic shock. Decrease in respiratory complex activity, increase in
free radical production, increase in mitochondrial synthase activity, increase in
nitric oxide production, and impair in electron transport system and/or
mitochondrial permeability are considered as the main factors responsible for
mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively
taken up by mitochondria and acts as a powerful antioxidant, regulating the
mitochondrial bioenergetic function. Melatonin increases the permeability of
membranes and is the stimulator of antioxidant enzymes including superoxide
dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also
acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation
damage by fixing the microsomal membranes. Melatonin has been shown to retard
aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic
shock, diabetes, cancer, and other complications related to oxidative stress. The
purpose of the current study, other than introducing melatonin, was to present
the recent findings on clinical effects in diseases related to mitochondrial
dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases
related to brain function.
PMID- 28400826
TI - The effect of Vitamin D supplementation in disease activity of systemic lupus
erythematosus patients with Vitamin D deficiency: A randomized clinical trial.
AB - BACKGROUND: The aim of this study was to check the effectiveness of Vitamin D
supplementation on the disease activity of Vitamin D-deficient systemic lupus
erythematosus (SLE) patients. MATERIALS AND METHODS: In this randomized, double
blind, placebo-controlled trial, 45 Vitamin D-deficient SLE patients were studied
in two groups, namely interventional and placebo groups. The interventional group
patients were treated with Vitamin D (50,000 unit/weekly Vitamin D for 12 weeks
and then 50,000 unit/monthly for 3 months) and placebo group patients were only
administered the placebo. The level of Vitamin D and the level of disease
activity using SLE disease activity index (SLEDAI) were measured before and after
intervention period in each group, and for intra- and between-groups comparison,
we used t-test and repeated measure ANOVA. RESULTS: A total of 90 patients were
enrolled in this study. The mean of Vitamin D was increased significantly after
therapy in interventional group (17.36 +/- 4.26 ng/ml vs. 37.69 +/- 5.92 ng/ml, P
< 0.001). The mean of Vitamin D had no significant difference before and after
intervention in placebo group (16.78 +/- 4.39 ng/ml vs. 16.62 +/- 4.61 ng/ml, P =
0.53). The mean of disease activity (SLEDAI) was not different significantly
before and after Vitamin D administration in interventional group (3.09 vs. 1.62
+/- 1.25, P = 0.39). The mean of disease activity (SLEDAI) was not different
significantly before and after intervention in placebo group (3.09 vs. 1.98 +/-
2.47, P = 0.42). CONCLUSION: According to our study, it is suggested that using
Vitamin D in patients with SLE could not have better outcomes in this regard.
However, there are many unknown environmental or biological factors which are
associated with the disease activity of SLE and have not been identified yet.
PMID- 28400827
TI - Effects of Vitamin D deficiency treatment on metabolic markers in Hashimoto
thyroiditis patients.
AB - BACKGROUND: The aim of the current trial was to investigate the effect of Vitamin
D treatment on metabolic markers in people with Vitamin D deficiency and thyroid
autoimmunity. MATERIALS AND METHODS: In this double-blind, randomized, placebo
controlled clinical trial, 65 Vitamin D deficient euthyroid or hypothyroid
patients with positive TPO-Ab were enrolled. They randomly allocated into two
groups to receive oral Vitamin D3 (50000 IU weekly) and placebo for 12 weeks.
Serum concentration of calcium, phosphorus, albumin, C-reactive protein, blood
urea nitrogen, creatinine, glycated hemoglobin (HbA1c), insulin, fasting plasma
glucose (FPG), triglyceride (TG), total cholesterol, and high-density lipoprotein
were measured in both groups before and after the trial. Homeostasis model
assessment estimates of beta cell function (HOMA-B) and HOMA-insulin resistance
(HOMA-IR) were calculated before and after trial in both groups. RESULTS: Thirty
three and thirty-two participants were allocated to Vitamin D-treated and placebo
treated groups, respectively. Mean (standard error) level of Vitamin D increased
significantly in Vitamin D-treated group (45.53 [1.84] ng/mL vs. 12.76 [0.74]
ng/mL, P = 0.001). The mean of HbA1c and insulin was increased significantly both
in Vitamin D-treated and placebo-treated groups (P < 0.05). Other variables did
not meet a significant change after trial (P = NS). In between-group comparison,
there was not any significant difference between Vitamin D-treated and placebo
treated groups regarding measures of HOMA-B, HOMA-IR, FPG, HbA1c, and TG (P =
NS). CONCLUSION: Our findings showed that weekly 50000 IU oral Vitamin D3 for 12
weeks did not improve metabolic markers, IR, or insulin secretion in Vitamin D
deficient patients with Hashimoto thyroiditis.
PMID- 28400828
TI - Effect of intrauterine injection of human chorionic gonadotropin before embryo
transfer on pregnancy rate: A prospective randomized study.
AB - BACKGROUND: Human chorionic gonadotropin (hCG) as the most important factor to
controlled implantation is one of the early embryonic signals in primates that is
secreted by the embryo before its implantation. This study was designed to assess
the effects of intrauterine injection of hCG before the embryo transfer in an in
vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle on
pregnancy rate in infertile patients. MATERIALS AND METHODS: This randomized
study was done on 100 infertile patients in two groups: intervention group
received injection of 700 IU of intrauterine hCG 10 min before embryo transfer
and control group did not receive hCG. The pregnancy rate was tested 2 weeks
after embryo transfer, and if the pregnancy test was positive, a transvaginal
ultrasound was performed 3 weeks later to search for signs of pregnancy, such as
the presence of a gestational sac, embryo, and fetal heart rate, and confirmed as
successful pregnancy. RESULTS: Pregnancy test was positive in 13 (28.6%) of 46
patients in hCG group and in control group was positive in 6 (12.5%) of 48
patients. The pregnancy rate between hCG group and control group was not
significantly different (P = 0.54). The pregnancy rate in hCG group with IVF
fertilization was 20.8% and in their controls was 7.4% (P = 0.51). The pregnancy
rate in hCG group with ICSI fertilization was 36.4% and in their controls was 19%
(P = 0.16). CONCLUSION: The intrauterine injection of 700 IU of hCG before embryo
transfer improved pregnancy rate compared to control group but was not
significantly different.
PMID- 28400830
TI - Plasma concentration, genetic variation, and gene expression levels of matrix
metalloproteinase 9 in Iranian patients with coronary artery disease.
AB - BACKGROUND: Matrix metalloproteinase 9 (MMP9) -1562C>T (rs3918242) polymorphism
has been proposed as a risk factor for coronary artery disease (CAD) with
conflicting results. The aim of the present study was to investigate the
association of -1562C>T genetic polymorphism, gene expression and circulating
levels of MMP9 with CAD risk in an Iranian subpopulation in in Zanjan City.
MATERIALS AND METHODS: This was a retrospective case-control study we
investigated retrospectively 100 patients with angiographically verified CAD and
100 matched controls. Genotyping of -1562C>T polymorphism was done by polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene
expression levels and circulating levels of MMP9 was determined by real-time
reverse transcription-PCR and enzyme immunoassay method, respectively.
Statistical analysis was done using Student's t-test or Chi-square test by SPSS
16 software. RESULTS: The mean circulating levels of MMP9 were significantly
higher in CAD Group than control group (P = 0.002). Mean plasma levels of MMP9
were also significantly higher in triple vessel stenosis patients than double
vessel or single vessel stenosis patients (P < 0.001). Moreover, mean plasma
levels and gene expression levels of MMP9 were significantly higher in T allele
carrier than C allele carrier of MMP9 -1562C>T polymorphism (P = 0.002, P = 0.01,
respectively). However, genotype and allele frequencies of MMP9 -1562C>T
polymorphism were similar between CAD patients and controls (P > 0.05).
Additionally, the -1562C>T polymorphism of MMP9 gene didn't increase the risk of
CAD in dominant (P = 0.537) or recessive (P = 0.249) genetic models. CONCLUSION:
Our study demonstrated that circulating levels of MMP9 but not -1562C>T
polymorphism of MMP9 gene may be a risk factor for development and severity of
CAD in an Iranian subpopulation in Zanjan.
PMID- 28400829
TI - A case-control study of bisphenol A and endometrioma among subgroup of Iranian
women.
AB - BACKGROUND: Endometriosis is a multifactorial hormonally related complex disease
with unknown etiology. Epidemiologic data were suggested the possible effects of
endocrine disrupting chemicals such as bisphenol A (BPA) on endometriosis. BPA is
similar to endogenous estrogen and has the ability to interact with estrogen
receptors and stimulate estrogen production. Our aim was to evaluate the
relationship between urinary BPA concentrations in women with endometrioma.
MATERIALS AND METHODS: This case-control study consisted of fifty women who have
been referred to gynecology and infertility center with endometrioma and were
candidates for operative laparoscopy and ovarian cystectomy as cases. Fifty women
who had not any evidence of endometrioma in clinical and ultrasound evaluation
and came to the same clinic for routine check-up were selected as controls. One
time urine sample was collected after receiving informed consent before surgery
and medical intervention. Total BPA in urine was measured with high-performance
liquid chromatography method and detection limit was 0.33 ng/mL. RESULTS:
Percentage of urine samples containing BPA was 86% of cases and 82.4% of control.
Urinary BPA showed a right-skewed distribution. The mean concentration of BPA was
5.53 +/- 3.47 ng/mL and 1.43 +/- 1.57 ng/mL in endometriosis and control group,
respectively (P < 0.0001, Mann-Whitney U-test). The logistic regression showed
that the odds ratio of the BPA was 1.74 (95% confidence interval: 1.40-2.16)
after adjustment of age, parity, body mass index <30, and educational status.
CONCLUSION: This study showed a positive association between urinary BPA
concentrations and endometrioma. However, further large-scale studies are needed
to confirm this hypothesis.
PMID- 28400831
TI - The relation between genital wart and multiple sclerosis.
PMID- 28400832
TI - The psychometric properties of the Persian version of Interpersonal Sensitivity
Measure.
AB - BACKGROUND: Investigating the psychometric properties of existing psychometric
scales in societies with differing dynamics can help with their external
validity. This research specifically aimed at standardization and validation of
Interpersonal Sensitivity Measure (IPSM) scale in Iran. MATERIALS AND METHODS:
Persian version of the IPSM was produced through forward translation,
reconciliation, and back translation. A total of 357, nonclinical students were
selected through multistage sampling method and completed a set of questionnaires
including IPSM. Internal consistency, convergent validity, divergent validity,
and test-retest reliability of the Persian version of the IPSM were analyzed. To
assess the construct validity, confirmatory factor analysis (CFA) was performed.
RESULTS: Total IPSM, as well as all subscales showed satisfactory internal
consistency (Cronbach's alpha =0.86 and 0.51-0.71, respectively). Test-retest
reliability at a 2-week interval was significant, with intraclass correlation
coefficient ranging between 0.73 and 0.92. In terms of convergent validity, IPSM
showed the significant positive correlation with self-report measures of
depression, social anxiety, and anxious attachment style. IPSM showed negative
correlation with Social Desirability Scale and secure (C subscale of avoidant
attachment style [AAS]) and dependent (D subscale of AAS), thus demonstrated
divergent validity with these constructs. According to the CFA, the responses of
the sample in this study were fitted to the original five-factor structure.
CONCLUSION: The IPSM showed good validity and reliability and could be useful in
assessing interpersonal sensitivity in Iranian population.
PMID- 28400833
TI - Over-expression of myosin7A in cochlear hair cells of circling mice.
AB - Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene
is an animal model for human non-syndromic recessive deafness, DFNB6. In circling
mouse, hair cells in the cochlea have degenerated and hair bundles have become
irregularity as time goes on. Tmie protein carries out a function of the
mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A)
protein has key roles in development of the cochlear hair bundles as well as in
the function of cochlear hair cells. To find whether Tmie protein interacts with
MYO7A proteins in the cochlea postnatal developmental stage, we investigated
expression of the MYO7A proteins in the cochlear hair cells of circling mice by
western blot analysis and whole mount immunofluorescence at postnatal day 5 (P5).
The expression of MYO7A showed statistically significant increase in the cochlea
of C57BL/6J-+/cir and C57BL/6J-cir/cir mice than that of C57BL/6J-+/+ mice. The
MYO7A intensity of the cochlear hair cells also increased in C57BL/6J-+/cir and
C57BL/6J-cir/cir mice compared with those of C57BL/6J-+/+ mice. Taken together,
the results indicate that Tmie protein may have an important role with MYO7A
protein in the development and maintenance of the stereociliary bundles during
postnatal developmental stage of the cochlea.
PMID- 28400834
TI - Comparison of commonly used ICR stocks and the characterization of Korl:ICR.
AB - Mouse is a commonly used animal in life science studies and is classified as
outbred if genetically diverse and inbred if genetically homogeneous. Outbred
mouse stocks, are used in toxicology, oncology, infection and pharmacology
research. The National Institute of Food and Drug Safety Evaluation (NIFDS;
former the Korea National Institute of Health) have bred ICR mice for more than
50 years. We investigated to provide users with information and promote
accountability to the Korl:ICR. To secure the indigenous data, biological
characteristics of Korl:ICR were identified by comparing with other ICR stocks.
This domestic ICR stock was denominated as 'Korl:ICR'. Phylogenetic analysis
using SNPs indicated that the population stratification of the Korl:ICR was
allocated different area with other ICR. In addition, we measured litter size,
body weight, body length, various organ weight, hematology and clinical blood
chemistry of the Korl:ICR compared to other ICR. Otherwise, there are no
significant differences among the biological phenotypes of Korl:ICR and other
ICR. These results suggest that as a genetically indigenous source colony, the
Korl:ICR is seperated (or independent) stock with other ICR. Also, we confirmed
that there is no difference among the Korl:ICR and other ICR on biological
phenotypes. Therefore, the Korl:ICR source colony might be a new stock in
distinction from other ICR, it is a good milestone in securing ownership of the
national laboratory animal resource. The NIFDS expects that the Korl:ICR mice
will be useful animal resource for our domestic researchers.
PMID- 28400835
TI - The effects of pentoxifylline adminstration on fracture healing in a
postmenopausal osteoporotic rat model.
AB - Previous studies report positive effects of pentoxifylline (PTX) alone or in
combination with other drugs on some pathologic bone diseases as well as an
ability to accelerate osteogensis and fracture healing in both animal models and
human patients. The aim of this present study was to evaluate the effects of PTX
administration on Hounsfield unit and bone strength at catabolic response (bone
resorbing) of a fracture in an experimental rat model of ovariectomy induced
osteoporosis (OVX-D). Thirty adult female rats were divided into groups as
follows: 1 (OVX, control, no treatment); 2 (OVX, sham: daily distilled water); 3
(OVX, daily alendronate: 3 mg/kg); 4 (OVX, twice daily 100 mg/kg PTX) and 5 (OVX,
PTX+alenderonate). OVX was induced by bilateral ovariectomy in all rats. A
complete standardized osteotomy of the right femur was made after 3.5 months. PTX
and alendronate treatments were performed for eight weeks. Then, rats were
euthanized and had its right femur subjected to computerized tomography scanning
for measuring Hounsfield unit; eventually, the samples were sent for a three
point bending test for evaluation of the bone strength. Administration of PTX
with 200 mg/kg and alendronate alone and in combination showed no significant
alteration in Hounsfield unit and biomechanical properties of repairing callus of
the complete osteotomy compared with the control group. Results showed increased
bending stiffness and stress high load mean values of repairing complete
osteotomy in PTX-treated rats compared to the control OVX-D.
PMID- 28400836
TI - Effects of coenzyme Q10 on the antioxidant system in SD rats exposed to
lipopolysaccharide-induced toxicity.
AB - The study was performed to see the effects of coenzyme Q10 (CoQ10) on blood
biochemical components and hepatic antioxidant system in rats exposed to
lipopolysaccharide (LPS)-induced toxicity. A total of 24 rats were allocated to
four groups: control (CON), 100 mg/kg BW of LPS (LPS), 100 mg of CoQ10/kg BW with
LPS (LCQI) and 300 mg of CoQ10/kg BW with LPS (LCQII). The LPS and LCQI groups
showed a significant (P<0.05) increase in the relative spleen weight compared
with the CON group without affecting body and liver weights. The blood alanine
aminotransferase (ALT) level in the LPS group was significantly (P<0.05) greater
than that in the CON group, while supplementation with 100 or 300 mg CoQ10 to
rats injected with LPS normalized the ALT level in the CON group. In antioxidant
systems, the LPS group showed a significantly (P<0.05) higher mRNA and activity
of superoxide dismutase (SOD) than the CON group. The supplementation with CoQ10
to the LPS-treated group normalized the level of SOD, which was comparable to the
level of the CON group. Both the mRNA expression and activity of glutathione
peroxidase in the LCQI and LCQII groups were higher (P<0.05) than that of the LPS
group. However, administration of LPS or CoQ10 unaffected the level of catalase
and total antioxidant power. The level of lipid peroxidation in the LCQII group
was lower (P<0.05) than that in the LPS group. In conclusion, CoQ10 exerted its
favorable effect against liver damage by modulation of antioxidant enzymes in LPS
treated rats.
PMID- 28400838
TI - HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette
smoke and lipopolysaccharide.
AB - HemoHIM, herbal preparation has designed for immune system recovery. We
investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and
lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD)
mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day
(eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26.
HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS
exposure. HemoHIM reduced the inflammatory cell count and levels of tumor
necrosis factor receptor (TNF)-alpha, interleukin (IL)-6 and IL-1beta in the
broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM
decreased the inflammatory cell infiltration in the airway and inhibited the
expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to
CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in
the lung inflammatory response on CS and LPS induced lung inflammation via the
Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat
pulmonary inflammatory disease such as COPD.
PMID- 28400837
TI - Immunomodulatory effects of ethanol extract of germinated ice plant
(Mesembryanthemum crystallinum).
AB - The purpose of this study was to investigate the immunomodulatory activity of ice
plant (Mesembryanthemum crystallinum) extract (IPE) in vitro and in vivo. Raji (a
human B cell line) and Jurkat (a human T cell line) cells were treated with
various doses of IPE and cell proliferation was measured by WST assay. Results
showed that IPE promoted the proliferation of both Raji and Jurkat cells in a
dose-dependent manner. IPE also enhanced IL-6 and TNF-alpha production in
macrophages in the presence of lipopolysaccharide (LPS), although IPE alone did
not induce cytokine production. Moreover, IPE treatment upregulated iNOS gene
expression in macrophages in a time- and dose-dependent manner and led to the
production of nitric oxide in macrophages in the presence of IFNgamma. In vivo
studies revealed that oral administration of IPE for 2 weeks increased the
differentiation of CD4+, CD8+, and CD19+ cells in splenocytes. These findings
suggested that IPE has immunomodulatory effects and could be developed as an
immunomodulatory supplement.
PMID- 28400839
TI - Effects of Inhalation Aromatherapy on Symptoms of Sleep Disturbance in the
Elderly with Dementia.
AB - This study investigated the effects of inhalation aromatherapy on sleep
disturbance in elderly individuals with dementia. In 19 subjects, normal sleep
was observed for a 20-day control period, inhalation aromatherapy was then
applied for a 20-day intervention period, and the control and intervention
periods were compared. During the intervention period, essential oils were placed
nightly on towels around the subjects' pillows. The measured sleep conditions
were sleep latency, total sleep time, sleep efficacy, duration of the longest
sustained sleep period, wake time after sleep onset, early morning awakening,
total daytime sleep, and the Neuropsychiatric Inventory. Total sleep time was
significantly longer in the intervention period than in the control period (p <
0.05). The duration of the longest sustained sleep period was significantly
longer in the intervention period than in the control period (p < 0.05). Early
morning awakening in the intervention period was significantly less compared to
that in the control period (p < 0.05). Total daytime sleep could not be
adequately measured and was omitted from the analysis. No significant differences
in other sleep conditions were observed. These results indicated positive effects
of inhalation aromatherapy on symptoms of sleep disturbance in elderly
individuals with dementia.
PMID- 28400840
TI - Comparative Evaluation of Sulfur Compounds Contents and Antiobesity Properties of
Allium hookeri Prepared by Different Drying Methods.
AB - Despite the nutritional and medicinal values of Allium hookeri, its unique flavor
(onion or garlic taste and smell) coming from sulfur containing compounds limits
its usage as functional food. For comparative study, A. hookeri roots were
prepared under two different drying conditions, namely, low-temperature drying
that minimizes the volatilization of sulfur components and hot-air drying that
minimizes the garlic odor and spicy taste of A. hookeri. In GC/MS olfactory
system, the odorous chemicals and organosulfur compounds such as diallyl
trisulfide, dimethyl trisulfide, and dipropyl trisulfide were significantly
decreased in hot-air drying compared to low-temperature drying. The spiciness and
saltiness taste were noticeably reduced, while sourness, sweetness, and umami
taste were significantly increased in hot-air dried A. hookeri according to
electronic tongue. Although the content of volatile sulfur components was present
at lower level, the administration of hot-air dried A. hookeri extract (100 mg/kg
p.o.) apparently prevented the body weight gain and improved insulin resistance
in C57BL/6J obese mice receiving high fat diet. Results suggested that the hot
air dried A. hookeri possessing better taste and odor might be available as
functional crop and bioactive diet supplement for the prevention and/or treatment
of obesity.
PMID- 28400841
TI - Effects of a Herbal Medicine, Yukgunja-Tang, on Functional Dyspepsia Patients
Classified by 3-Dimensional Facial Measurement: A Study Protocol for Placebo
Controlled, Double-Blind, Randomized Trial.
AB - Introduction. Functional dyspepsia (FD), a common upper gastrointestinal disease,
is difficult to manage because of the limitations of current conventional
treatments. Yukgunja-tang (YGJT) is widely used to treat FD in clinical practice
in Korea, Japan, and China. However, YGJT significantly improves few symptoms of
FD. In Korean medicine, FD is a well-known functional gastric disease that shows
difference in the effect of herbal medicine depending on constitution or type of
Korean medicine diagnosis. This study aims to investigate the efficacy of YGJT on
FD patients classified by 3-dimensional facial measurement using a 3-dimensional
facial shape diagnostic system (3-FSDS). Methods. A placebo-controlled, double
blind, randomized, two-center trial will be performed to evaluate the efficacy of
YGJT on FD patients. Eligible subjects will be initially classified as two types
by 3-dimensional facial measurement using the 3-FSDS. Ninety-six subjects (48
subjects per each type) will be enrolled. These subjects will be randomly
allocated into treatment or control groups in a 2 : 1 ratio. YGJT or placebo will
be administered to each group during the 8-week treatment period. The primary
outcome is total dyspepsia symptom scale, and the secondary outcomes include
single dyspepsia symptom scale, proportion of responders with adequate symptom
relief, visual analog scale, Nepean dyspepsia index-Korean version, functional
dyspepsia-related quality of life, and spleen qi deficiency questionnaire.
Discussion. This is the first randomized controlled trial to assess the efficacy
of the YGJT on FD patients classified by 3-dimensional facial measurement. We
will compare the treatment effect of the YGJT on FD patients classified as two
types using the 3-FSDS. The results of this trial will help the FD patients
improve the symptoms and quality of life effectively and provide objective
evidence for prescribing the YGJT to FD patients in clinical practice. Trial
Registration. This trial is registered with Clinical Research Information Service
Identifier: KCT0001920, 15 May, 2016.
PMID- 28400842
TI - Tongxinluo Regulates Expression of Tight Junction Proteins and Alleviates
Endothelial Cell Monolayer Hyperpermeability via ERK-1/2 Signaling Pathway in
Oxidized Low-Density Lipoprotein-Induced Human Umbilical Vein Endothelial Cells.
AB - Vascular hyperpermeability resulting from distortion of endothelial junctions is
associated with a number of cardiovascular diseases. Endothelial tight junction
regulates the paracellular permeability of macromolecules, a function of Human
Umbilical Vein Endothelial Cells (HUVEC) monolayers that can be regulated by
oxidized Low-density Lipoprotein (ox-LDL). However, the understanding of drug
regulation of vascular hyperpermeability is so far limited. This study thus aimed
to investigate the role of Tongxinluo (TXL) in the maintenance of the vascular
endothelial paracellular permeability. Here, changes in permeability were
determined by measuring the paracellular flux of FITC-dextran 40000 (FD40), while
protein expression and intercellular distribution were examined by western blot
and immunofluorescence assay, respectively. We found that TXL alleviated the ox
LDL-induced increase in flux of FD40 and then reduced the hyperpermeability.
Moreover, ox-LDL-induced disruptions of ZO-1, occludin, and claudin1 were also
restored. This is via the activation of ERK1/2 in the vascular endothelial cells.
Our results provide insights into the molecular mechanism by which TXL alleviates
ox-LDL-induced hyperpermeability and provide the basis for further investigations
of TXL as regulators of vascular barrier function.
PMID- 28400843
TI - Acute and Subacute Oral Toxicity Evaluation of Eriobotrya japonica Leaf
Triterpene Acids in ICR Mice.
AB - The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has
increased recently because of its beneficial effects on health. However, there
has been a lack of experimental data on its toxicity. The present study therefore
was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA
produced neither mortality nor toxicity of the main organs in ICR male and female
mice in both acute (0.30, 0.65, 1.39, and 3.00 g.kg-1 body weight) and subacute
(150, 300, and 600 mg.kg-1 BW) 28-day toxicity studies. Because of lacking
apparently adverse effects found in the hematology, clinical biochemistry, and
histopathology evaluation, results of the present study together with the
beneficial effects make ELTA as a promising dietary supplement and indicated that
ELTA administered orally might have a large safety margin for human.
PMID- 28400844
TI - Effects of Electroacupuncture on Methamphetamine-Induced Behavioral Changes in
Mice.
AB - Methamphetamine (METH) is a major drug of abuse worldwide, and no efficient
therapeutic strategies for treating METH addiction are currently available.
Continuous METH use can cause behavioral upregulation or psychosis. The
dopaminergic pathways, particularly the neural circuitry from the ventral
tegmental area to the nucleus accumbens (NAc), have a critical role in this
behavioral stage. Acupuncture has been used for treating diseases in China for
more than 2000 years. According to a World Health Organization report,
acupuncture can be used to treat several functional disorders, including
substance abuse. In addition, acupuncture is effective against opioids addiction.
In this study, we used electroacupuncture (EA) for treating METH-induced
behavioral changes and investigated the possible therapeutic mechanism. Results
showed that EA at the unilateral Zhubin (KI9)-Taichong (LR3) significantly
reduced METH-induced behavioral sensitization and conditioned place preference.
In addition, both dopamine and tyrosine hydroxylase (TH) levels decreased but
monoamine oxidase A (MAO-A) levels increased in the NAc of the METH-treated mice
receiving EA compared with those not receiving EA. EA may be a useful
nonpharmacological approach for treating METH-induced behavioral changes,
probably because it reduces the METH-induced TH expression and dopamine levels
and raises MAO-A expression in the NAc.
PMID- 28400845
TI - Wound Healing Effects of Prunus yedoensis Matsumura Bark in Scalded Rats.
AB - Pruni Cortex has been used to treat asthma, measles, cough, urticaria, pruritus,
and dermatitis in traditional Korean medicine. The objective of this study was to
investigate the effects of Prunus yedoensis Matsumura bark methanol extract (PYE)
on scald-induced dorsal skin wounds in rats. Scalds were produced in Sprague
Dawley rats with 100 degrees C water and treated with 5% and 20% PYE (using
Vaseline as a base), silver sulfadiazine (SSD), and Vaseline once a day for 21
days, beginning 24 hours after scald by treatment group allocation. The PYE
treated groups showed accelerated healing from 12 days after scald, demonstrated
by rapid eschar exfoliation compared to the control and SSD groups. PYE-treated
groups showed higher wound contraction rates and better tissue regeneration in
comparison with the control group. Serum analysis showed that transforming growth
factor beta 1 and vascular endothelial growth factor levels remained high or
gradually increased up to day 14 in both PYE groups and then showed a sharp
decline by day 21, implying successful completion of the inflammatory phase and
initiation of tissue regeneration. These findings suggested that PYE is effective
in promoting scald wound healing in the inflammation and tissue proliferation
stages.
PMID- 28400846
TI - Lifestyle-Related Factors in the Self-Management of Chemotherapy-Induced
Peripheral Neuropathy in Colorectal Cancer: A Systematic Review.
AB - Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse
effect of chemotherapy treatment in colorectal cancer (CRC), negatively affecting
the daily functioning and quality of life of CRC patients. Currently, there are
no established treatments to prevent or reduce CIPN. The purpose of this
systematic review was to identify lifestyle-related factors that can aid in
preventing or reducing CIPN, as such factors may promote self-management options
for CRC patients suffering from CIPN. Methods. A literature search was conducted
through PubMed, Embase, and Google Scholar. Original research articles
investigating oxaliplatin-related CIPN in CRC were eligible for inclusion.
Results. In total, 22 articles were included, which suggested that dietary
supplements, such as antioxidants and herbal extracts, as well as physical
exercise and complementary therapies, such as acupuncture, may have beneficial
effects on preventing or reducing CIPN symptoms. However, many of the reviewed
articles presented various limitations, including small sample sizes and
heterogeneity in study design and measurements of CIPN. Conclusions. No strong
conclusions can be drawn regarding the role of lifestyle-related factors in the
management of CIPN in CRC patients. Certain dietary supplements and physical
exercise may be beneficial for the management of CIPN, but further research is
warranted.
PMID- 28400847
TI - Gengnianchun, a Traditional Chinese Medicine, Enhances Oxidative Stress
Resistance and Lifespan in Caenorhabditis elegans by Modulating daf-16/FOXO.
AB - Objective. Gengnianchun (GNC), a traditional Chinese medicine (TCM), is primarily
used to improve declining functions related to aging. In this study, we
investigated its prolongevity and stress resistance properties and explored the
associated regulatory mechanism using a Caenorhabditis elegans model. Methods.
Wild-type C. elegans N2 was used for lifespan analysis and oxidative stress
resistance assays. Transgenic animals were used to investigate pathways
associated with antioxidative stress activity. The effects of GNC on levels of
reactive oxygen species (ROS) and expression of specific genes were examined.
Results. GNC-treated wild-type worms showed an increase in survival time under
both normal and oxidative stress conditions. GNC decreased intracellular ROS
levels by 67.95%. GNC significantly enhanced the oxidative stress resistance of
several mutant strains, suggesting that the protective effect of GNC is
independent of the function of these genes. However, the oxidative stress
resistance effect of GNC was absent in worms with daf-16 mutation. We also found
upregulation of daf-16 downstream targets including sod-3 and mtl-1. Conclusions.
Our findings suggest that GNC extends the lifespan of C. elegans and enhances its
resistance to oxidative stress via a daf-16/FOXO-dependent pathway. This study
also provides a feasible method for screening the biological mechanisms of TCMs.
PMID- 28400848
TI - The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the
Literature.
AB - Tulsi, also known as holy basil, is indigenous to the Indian continent and highly
revered for its medicinal uses within the Ayurvedic and Siddha medical systems.
Many in vitro, animal and human studies attest to tulsi having multiple
therapeutic actions including adaptogenic, antimicrobial, anti-inflammatory,
cardioprotective, and immunomodulatory effects, yet to date there are no
systematic reviews of human research on tulsi's clinical efficacy and safety. We
conducted a comprehensive literature review of human studies that reported on a
clinical outcome after ingestion of tulsi. We searched for studies published in
books, theses, conference proceedings, and electronic databases including
Cochrane Library, Google Scholar, Embase, Medline, PubMed, Science Direct, and
Indian Medical databases. A total of 24 studies were identified that reported
therapeutic effects on metabolic disorders, cardiovascular disease, immunity, and
neurocognition. All studies reported favourable clinical outcomes with no studies
reporting any significant adverse events. The reviewed studies reinforce
traditional uses and suggest tulsi is an effective treatment for lifestyle
related chronic diseases including diabetes, metabolic syndrome, and
psychological stress. Further studies are required to explore mechanisms of
action, clarify the dosage and dose form, and determine the populations most
likely to benefit from tulsi's therapeutic effects.
PMID- 28400849
TI - Cytotoxicity and Apoptosis Induction of Ardisia crispa and Its Solvent Partitions
against Mus musculus Mammary Carcinoma Cell Line (4T1).
AB - This study was conducted to investigate the cytotoxicity and apoptosis effect of
A. crispa extract and its solvent partition (ethyl acetate and aqueous extract)
against Mus musculus mammary carcinoma cell line (4T1). The normal mouse
fibroblast cell line (NIH3T3) was used as comparison for selective cytotoxicity
properties. The cytotoxicity evaluation was assessed using MTT assay. AO/PI dual
fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis.
Results showed that 80% methanol extract from leaves showed most promising
antimammary cancer agent with IC50 value of 42.26 +/- 1.82 MUg/mL and selective
index (SI) value of 10.22. Ethyl acetate was cytotoxic for both cancer and normal
cell while aqueous extract exhibited poor cytotoxic effect. 4T1 cells labelled
with AO/PI and Annexin V-FITC and treated with 80% methanol extract demonstrated
that the extract induces apoptosis to 4T1 mammary cancer cells. In conclusion,
80% methanol extract of A. crispa was selectively cytotoxic towards 4T1 cells but
less cytotoxic towards NIH3T3 cells and induced the cancerous cells into
apoptotic stage as early as 6 hours.
PMID- 28400850
TI - Validity assessment of the PROMIS fatigue domain among people living with HIV.
AB - PURPOSE: To evaluate psychometric characteristics and cross-sectional and
longitudinal validity of the 7-item PROMIS(r) Fatigue Short Form and additional
fatigue items among people living with HIV (PLWH) in a nationally distributed
network of clinics collecting patient reported data at the time of routine
clinical care. METHODS: Cross-sectional and longitudinal fatigue data were
collected from September 2012 through April 2013 across clinics participating in
the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We
analyzed data regarding psychometric characteristics including simulated
computerized adaptive testing and differential item functioning, and regarding
associations with clinical characteristics. RESULTS: We analyzed data from 1597
PLWH. Fatigue was common in this cohort. Scores from the PROMIS(r) Fatigue Short
Form and from the item bank had acceptable psychometric characteristics and
strong evidence for validity, but neither performed better than shorter
instruments already integrated in CNICS. CONCLUSIONS: The PROMIS(r) Fatigue Item
Bank is a valid approach to measuring fatigue in clinical care settings among
PLWH, but in our analyses did not perform better than instruments associated with
less respondent burden.
PMID- 28400851
TI - What influences quality of life in older people living with HIV?
AB - BACKGROUND: People with HIV with access to treatment are growing older and living
healthier lives than in the past, and while health improvements and increased
survival rates are welcome, the psychological and social consequences and quality
of life of ageing are complex for this group. Understanding how ageing, HIV and
quality of life intersect is key to developing effective interventions to improve
QoL. METHODS: One hundred people with HIV over the age of 50 (range 50-87, mean
58), were recruited through HIV community organizations, and clinics, and
included men who have sex with men (MSM), and Black African and White
heterosexual men and women. The WHOQOL-HIV BREF was used, as well as the Every
Day Memory Questionnaire, and additional questions on anxiety and depression to
supplement the WHOQOL. RESULTS: While most rated their quality of life (QoL)
positively, bivariate analysis showed that better QoL (total score and most
domains) was strongly associated with being a man; in a relationship; in paid
employment; having higher level of income; not on benefits, and to a lesser
degree with being MSM, having higher level of education, and diagnosed after the
age of 40. Multivariate analysis showed that not being on benefits was the
variable most consistently associated with better quality of life, as was being
partnered. Concerns about everyday memory difficulties, and anxiety and
depression scores were strong predictors of poorer quality of life. CONCLUSION:
While the cross-sectional nature of the investigation could not establish that
the associations were causal, the findings indicate that concerns about memory
difficulties, anxiety and depression, as well as gender, ethnicity, financial
factors, and relationship status, are important contributors to QoL in this
group. These findings point towards the need for further research to clarify the
mechanisms through which the factors identified here affect QoL, and to identify
possible interventions to improve the QoL of older people living with HIV.
PMID- 28400852
TI - Effect of diet on the structure of animal personality.
AB - There is increasing interest in the proximate factors that underpin individual
variation in suites of correlated behaviours. In this paper, we propose that
dietary macronutrient composition, an underexplored environmental factor, might
play a key role. Variation in macronutrient composition can lead to among
individual differentiation in single behaviours ('personality' ) as well as among
individual covariation between behaviours ('behavioural syndromes' ). Here, we
argue that the nutritional balance during any life stage might affect the
development of syndrome structure and the expression of genes with pleiotropic
effects that influence development of multiple behaviours, hence genetic syndrome
structure. We further suggest that males and females should typically differ in
diet-dependent genetic syndrome structure despite a shared genetic basis. We
detail how such diet-dependent multivariate gene-environment interactions can
have major repercussions for the evolution of behavioural syndromes.
PMID- 28400853
TI - Domestication affects the structure, development and stability of biobehavioural
profiles.
AB - Domestication is an evolutionary process during which the biobehavioural profile
(comprising e.g. social and emotional behaviour, cognitive abilities, as well as
hormonal stress responses) is substantially reshaped. Using a comparative
approach, and focusing mainly on the domestic and wild guinea pig, an established
model system for the study of domestication, we review (a) how wild and domestic
animals of the same species differ in behaviour, emotion, cognition, and hormonal
stress responses, (b) during which phases of life differences in biobehavioural
profiles emerge and (c) whether or not animal personalities exist in both the
wild and domestic form. Concerning (a), typical changes with domestication
include increased courtship, sociopositive and maternal behaviours as well as
decreased aggression and attentive behaviour. In addition, domestic animals
display more anxiety-like and less risk-taking and exploratory behaviour than the
wild form and they show distinctly lower endocrine stress responsiveness. There
are no indications, however, that domestic animals have diminished cognitive
abilities relative to the wild form. The different biobehavioural profiles of the
wild and domestic animals can be regarded as adaptations to the different
environmental conditions under which they live, i.e., the natural habitat and
artificial man-made housing conditions, respectively. Concerning (b), the
comparison of infantile, adolescent and adult wild and domestic guinea pigs shows
that the typical biobehavioural profile of the domestic form is already present
during early phases of life, that is, during early adolescence and weaning. Thus,
differences between the domestic and the wild form can be attributed to genetic
alterations resulting from artificial selection, and likely to environmental
influences during the pre- and perinatal phase. Interestingly, the frequency of
play behaviour does not differ between the domestic and wild form early in life,
but is significantly higher in domesticated guinea pigs at later ages. Concerning
(c), there is some evidence that personalities occur in both wild and domestic
animals. However, there may be differences in which behavioural domains - social
and sexual behaviour, emotionality, stress-responsiveness - are consistent over
time. These differences are probably due to changing selection pressures during
domestication.
PMID- 28400854
TI - A rapid and efficient method for uniform gene expression using the barley stripe
mosaic virus.
AB - BACKGROUND: The barley stripe mosaic virus (BSMV) has become a popular vector to
study gene function in cereals. However, studies have been limited to gene
silencing in leaves of barley or wheat. In addition, the method produces high
variability between different leaves and plants. To overcome these limitations,
we explored the potential of modifying the inoculation protocol for BSMV gene
overexpression. An improved light, oxygen or voltage-sensing (iLOV) domain-based
fluorescent protein was used as a reporter of gene expression to monitor the
infection and spread of BSMV. Tobacco (Nicotiana benthamiana) leaves were
infected via agroinfiltration and the leaves were homogenized to extract the BSMV
particles and inoculate wheat tissues using the traditional leaf abrasion method
or by incubation during seed imbibition in a Petri dish. RESULTS: Compared to the
leaf abrasion method, the seed imbibition method resulted in a high and uniform
detection of iLOV in both roots and leaves of different wheat cultivars and other
monocot and dicot species within 7 days after germination. The progression of
viral infection via the imbibition method as measured by the expression of iLOV
was more stable in different organs and tissues and is transmissible to the next
generation. CONCLUSION: Our results show that BSMV can be used as a vector for
the expression of small genes such as iLOV in wheat roots and leaves. The
inoculation by seed imbibition allows genes to be expressed rapidly and uniformly
in wheat and different monocot and dicot species compared to the traditional leaf
abrasion method. It also produces high successful transformation as early as 7
days post infection allowing gene function studies during the first generation of
infected plants. Furthermore, the method is simple, rapid, and inexpensive
compared to the production of transgenic plants.
PMID- 28400855
TI - Ex vitro hairy root induction in detached peanut leaves for plant-nematode
interaction studies.
AB - BACKGROUND: Peanut (Arachis hypogaea) production is largely affected by a variety
of abiotic and biotic stresses, including the root-knot nematode (RKN)
Meloidogyne arenaria that causes yield losses worldwide. Transcriptome studies of
wild Arachis species, which harbor resistance to a number of pests and diseases,
disclosed several candidate genes for M. arenaria resistance. Peanut is
recalcitrant to genetic transformation, so the use of Agrobacterium rhizogenes
derived hairy roots emerged as an alternative for in-root functional
characterization of these candidate genes. RESULTS: The present report describes
an ex vitro methodology for hairy root induction in detached leaves based on the
well-known ability of peanut to produce roots spontaneously from its petiole,
which can be maintained for extended periods under high-humidity conditions.
Thirty days after infection with the A. rhizogenes 'K599' strain, 90% of the
detached leaves developed transgenic hairy roots with 5 cm of length in average,
which were then inoculated with M. arenaria. For improved results, plant
transformation, and nematode inoculation parameters were adjusted, such as
bacterial cell density and growth stage; moist chamber conditions and nematode
inoculum concentration. Using this methodology, a candidate gene for nematode
resistance, AdEXLB8, was successfully overexpressed in hairy roots of the
nematode-susceptible peanut cultivar 'Runner', resulting in 98% reduction in the
number of galls and egg masses compared to the control, 60 days after M. arenaria
infection. CONCLUSIONS: This methodology proved to be more practical and cost
effective for functional validation of peanut candidate genes than in vitro and
composite plant approaches, as it requires less space, reduces analysis costs and
displays high transformation efficiency. The reduction in the number of RKN galls
and egg masses in peanut hairy roots overexpressing AdEXLB8 corroborated the use
of this strategy for functional characterization of root expressing candidate
genes. This approach could be applicable not only for peanut-nematode interaction
studies but also to other peanut root diseases, such as those caused by fungi and
bacteria, being also potentially extended to other crop species displaying
similar petiole-rooting competence.
PMID- 28400856
TI - Glossogyne tenuifolia (Hsiang-ju) extract suppresses T cell activation by
inhibiting activation of c-Jun N-terminal kinase.
AB - BACKGROUND: Glossogyne tenuifolia (GT) (Hsiang-ju) is a Chinese herbal medicine
previously exhibited an anti-inflammatory activity. This study aimed to
investigate the effect of GT ethanol extract (GTE) on T cell-mediated adaptive
immunity. METHODS: Human peripheral blood mononuclear cells (PBMCs) and Jurkat T
cells were activated by phytohemagglutinin in the presence of various doses (3.13
50 MUg/mL) of GTE. The effect of GTE on T cell activation was examined by a
proliferation assay of activated PBMCs and the level of the activation marker
CD69 on the surface of activated Jurkat T cells. Apoptosis was determined by
propidium iodide staining in hypotonic solution. Signaling pathway molecules were
assessed by western blotting. RESULTS: Glossogyne tenuifolia ethanol extract was
demonstrated to inhibit T cell activation, not only in the proliferation of human
PBMCs at the concentrations of 12.5, 25 and 50 MUg/mL (P = 0.0118, 0.0030 and
0.0021) but also in the CD69 expression in Jurkat cells, which was not due to the
cytotoxicity of GTE. The presence of GTE did not change the activity of nuclear
factor kappa-light-chain-enhancer of activated B cells or extracellular signal
regulated kinase upon T cell activation. In addition, GTE significantly reduced
activation of c-Jun N-terminal kinase (JNK) (P = 0.0167) and p38 (P = 0.0278).
Furthermore, decreased JNK activation mediated the preventive effect of GTE on T
cell activation-induced cell death (AICD). CONCLUSION: Glossogyne tenuifolia
ethanol extract inhibited T cell activation of Jurkat cells and freshly prepared
human PBMCs due to suppression of JNK activity. Furthermore, GTE inhibited AICD
by blocking prolonged JNK phosphorylation in activated T cells. Taken together,
the anti-inflammatory effects exerted by GTE were mediated via suppression of JNK
phosphorylation in T cell activation.
PMID- 28400857
TI - Estimation of the overall burden of cancers, precancerous lesions, and genital
warts attributable to 9-valent HPV vaccine types in women and men in Europe.
AB - BACKGROUND: In addition to cervical cancer, human papillomavirus (HPV) is
responsible for a significant proportion of cancers and precancerous lesions of
the vulva, vagina, anus, penis, head and neck, as well as genital warts. We
estimated the annual number of new cases of these diseases attributable to 9
valent HPV vaccine types in women and men in Europe. METHODS: The annual number
of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and
neck sites in the population of the European Medicines Agency territory was
estimated based on age-specific incidence rates extracted from Cancer Incidence
in 5 Continents, Volume X and Eurostat population data for 2015. The annual
number of new cancers attributable to 9-valent HPV vaccine types was estimated by
applying the HPV attributable fraction from reference publications based on a
large European multicenter study. For non-cervical cancers, HPV attributable
fractions were based on oncogenically-active HPV infections only (i.e., detection
of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of
the cervix, vulva, vagina, and anus, and for genital warts, previously published
estimations were updated for the 2015 population. RESULTS: The annual number of
new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992
(95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130
cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137
cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile
cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men.
The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and
AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was
estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively.
CONCLUSIONS: The burden of cancers associated with 9-valent HPV vaccine types in
Europe is substantial in both sexes. Head and neck cancers constitute a heavy
burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of
precancerous lesions, and 90% of genital warts are expected to be attributable to
9-valent HPV vaccine types each year, demonstrating the important preventive
potential of the 9-valent HPV vaccine in Europe.
PMID- 28400858
TI - Multi-product biorefineries from lignocelluloses: a pathway to revitalisation of
the sugar industry?
AB - BACKGROUND: Driven by a range of sustainability challenges, e.g. climate change,
resource depletion and expanding populations, a circular bioeconomy is emerging
and expected to evolve progressively in the coming decades. South Africa along
with other BRICS countries (Brazil, Russia, India and China) represents the
emerging bioeconomy and contributes significantly to global sugar market. In our
research, South Africa is used as a case study to demonstrate the sustainable
design for the future biorefineries annexed to existing sugar industry. Detailed
techno-economic evaluation and Life Cycle Assessment (LCA) were applied to model
alternative routes for converting sugarcane residues (bagasse and trash) to
selected biofuel and/or biochemicals (ethanol, ethanol and lactic acid, ethanol
and furfural, butanol, methanol and Fischer-Tropsch synthesis, with co-production
of surplus electricity) in an energy self-sufficient biorefinery system. RESULTS:
Economic assessment indicated that methanol synthesis with an internal rate of
return (IRR) of 16.7% and ethanol-lactic acid co-production (20.5%) met the
minimum investment criteria of 15%, while the latter had the lowest sensitivity
to market price amongst all the scenarios. LCA results demonstrated that
sugarcane cultivation was the most significant contributor to environmental
impacts in all of the scenarios, other than the furfural production scenario in
which a key step, a biphasic process with tetrahydrofuran solvent, had the most
significant contribution. CONCLUSION: Overall, the thermochemical routes
presented environmental advantages over biochemical pathways on most of the
impact categories, except for acidification and eutrophication. Of the
investigated scenarios, furfural production delivered the inferior environmental
performance, while methanol production performed best due to its low reagent
consumption. The combined techno-economic and environmental assessments
identified the performance-limiting steps in the 2G biorefinery design for
sugarcane industry and highlighted the technology development opportunities under
circular bioeconomy context.
PMID- 28400859
TI - Precise pretreatment of lignocellulose: relating substrate modification with
subsequent hydrolysis and fermentation to products and by-products.
AB - BACKGROUND: Pretreatment is a crucial step for valorization of lignocellulosic
biomass into valuable products such as H2, ethanol, acids, and methane. As
pretreatment can change several decisive factors concurrently, it is difficult to
predict its effectiveness. Furthermore, the effectiveness of pretreatments is
usually assessed by enzymatic digestibility or merely according to the yield of
the target fermentation products. The present study proposed the concept of
"precise pretreatment," distinguished the major decisive factors of
lignocellulosic materials by precise pretreatment, and evaluated the complete
profile of all fermentation products and by-products. In brief, hemicellulose and
lignin were selectively removed from dewaxed rice straw, and the cellulose was
further modified to alter the crystalline allomorphs. The subsequent fermentation
performance of the selectively pretreated lignocellulose was assessed using the
cellulolytic, ethanologenic, and hydrogenetic Clostridium thermocellum through a
holistic characterization of the liquid, solid, and gaseous products and
residues. RESULTS: The transformation of crystalline cellulose forms from I to II
and from Ialpha to Ibeta improved the production of H2 and ethanol by 65 and 29%,
respectively. At the same time, the hydrolysis efficiency was merely improved by
10%, revealing that the crystalline forms not only influenced the accessibility
of cellulose but also affected the metabolic preferences and flux of the system.
The fermentation efficiency was independent of the specific surface area and
degree of polymerization. Furthermore, the pretreatments resulted in 43-45% of
the carbon in the liquid hydrolysates unexplainable by forming ethanol and
acetate products. A tandem pretreatment with peracetic acid and alkali improved
ethanol production by 45.5%, but also increased the production of non-ethanolic
low-value by-products by 136%, resulting in a huge burden on wastewater treatment
requirements. CONCLUSION: Cellulose allomorphs significantly affected
fermentation metabolic pathway, except for hydrolysis efficiency. Furthermore,
with the increasing effectiveness of the pretreatment for ethanol production,
more non-ethanolic low-value by-products or contaminants were produced,
intensifying environmental burden. Therefore, the effectiveness of the
pretreatment should not only be determined on the basis of energy auditing and
inhibitors generated, but should also be assessed in terms of the environmental
benefits of the whole integrated system from a holistic view.
PMID- 28400860
TI - Multiple etiologies of infectious diarrhea and concurrent infections in a
pediatric outpatient-based screening study in Odisha, India.
AB - BACKGROUND: There are multiple etiologies responsible for infectious
gastroenteritis causing acute diarrhea which are often under diagnosed. Also
acute diarrhea is one of the major causes of morbidity and mortality among
children less than 5 years of age. METHODS: In our study, fecal samples (n = 130)
were collected from children (<5 years) presenting with symptoms of acute
diarrhea. Samples were screened for viral, bacterial, and parasitic etiologies.
Rotavirus and Adenovirus were screened by immunochromatographic tests.
Diarrheagenic Escherichia coli (EPEC, EHEC, STEC, EAEC, O157, O111), Shigella
spp., Salmonella spp., Vibrio cholera, Cryptosporidium spp., and Giardia spp.
were detected by gene-specific polymerase chain reaction. RESULTS: Escherichia
coli was detected to be the major etiological agent (30.07%) followed by
Rotavirus (26.15%), Shigella (23.84%), Adenovirus (4.61%), Cryptosporidium
(3.07%), and Giardia (0.77%). Concurrent infections with two or more pathogens
were observed in 44 of 130 (33.84%) cases with a predominant incidence
particularly in <2-year-old children (65.90%) compared to children of 2-5 years
age group (34.09%). An overall result showed significantly higher detection rates
among children with diarrhea in both combinations of two as well as three
infections concurrently (p = 0.004915 and 0.03917, respectively). CONCLUSION:
Suspecting possible multiple infectious etiologies and diagnosis of the right
causative agent(s) can aid in a better pharmacological management of acute
childhood diarrhea. It is hypothesized that in cases with concurrent infections
the etiological agents might be complementing each other's strategies of
pathogenesis resulting in severe diarrhea that could be studied better in
experimental infections.
PMID- 28400861
TI - Revision of Echocardiographic Indications and Findings in Neurologically Ill
Patients.
AB - BACKGROUND AND OBJECTIVE: Little is known about the general indications for
echocardiography and the prevalence of abnormalities detected by echocardiography
in patients who are referred from a neurological department. Left ventricular
hypertrabeculation/noncompaction (LVHT) is associated with neuromuscular
disorders and embolism. The aim of the study was to assess the indications for
echocardiography in patients from a neurological department and to review the
cine-loops of the examinations in order to assess the frequency of abnormal
echocardiographic findings with special regard to LVHT. METHODS AND RESULTS:
Included were 126 patients, 58 females (mean age 65 years). Indications were
stroke (84%), heart failure (6%), endocarditis (6%) and arrhythmia (3%). The most
frequent abnormalities were impaired relaxation (71%) and left ventricular wall
thickening (63%). Females were older (68 vs. 62 years, p = 0.0214) and more
frequently had normally sized left ventricles than males (98 vs. 88%, p =
0.0376). Patients >=66 years more frequently had stroke as an indication (91 vs.
77%, p = 0.05), showed a thickened myocardium (72 vs. 53%, p = 0.0272), valvular
abnormalities (52 vs. 13%, p = 0.0000) and impaired relaxation (86 vs. 54%, p =
0.0001) than patients <66 years. LVHT was diagnosed in 3 patients; in one of them
the diagnosis was already known. In 45% LVHT and in 38% left ventricular thrombus
could neither be excluded nor established since the image quality was poor.
CONCLUSION: Care should be taken to visualize the left ventricular apical regions
when investigating patients referred from a neurologic department in order not to
overlook LVHT and thrombi within the left ventricular apex.
PMID- 28400862
TI - An Audit of Clinical Practice in a Single Centre in Kuwait: Management of
Children on Continuous Subcutaneous Insulin Infusion and Cardiovascular Risk
Factors Screening.
AB - OBJECTIVES: To audit the current clinical practice of continuous subcutaneous
insulin infusion (CSII) for the treatment of type 1 diabetes mellitus (T1D) in
children and adolescents attending a single centre in Kuwait. METHODS: A one year
retrospective audit was performed in children and adolescents with T1D on CSII,
who attended the paediatric diabetes clinic, Dasman Diabetes Institute during
2012. The primary outcome measure was glycaemic control as evidenced by glycated
haemoglobin (HbA1c) level and the secondary outcome measures were the frequency
of monitoring of the risk for microvascular complications and occurrence of acute
complications and adverse events. RESULTS: 58 children and adolescents (mean age
+/- SD: 12.6 +/- 4.1 years) were included. Mean HbA1c at baseline was 8.8% (72.7
mmol/mol) and 8.9% (73.8 mmol/mol) at the end of a 12 months observation period.
Children with poor control (HbA1c >9.5% (80 mmol/mol) had a significant 1.4%
reduction in HbA1c compared with the overall reduction of 0.1% (p=0.7). Rate of
screening for cardiovascular risk factors and for long term complications were
well documented. However, there was underreporting of acute complications such as
severe hypoglycaemia and diabetic ketoacidosis. Only 1.7% of patients
discontinued the pump. CONCLUSION: There was no significant change in HbA1c
values at the end of 12 months follow up. However, HbA1c values in poorly
controlled children improved. CSII requires care by skilled health professionals
as well as education and selection of motivated parents and children.
PMID- 28400863
TI - Prevalence of the Short Face Pattern in Individuals of Bauru-Brazil.
AB - AIM: This study aimed at assessing the prevalence and severity of short face
pattern in ethnically different individuals. MATERIAL AND METHODS: The sample
comprised 4,409 Brazilians (2,192 females and 2,217 males), with a mean age of 13
years, enrolled in secondary schools in the municipality of Bauru. The sample
inclusion criteria involved subjects with vertically impaired facial relationship
based on excessive lip compression, when standing at natural head position, with
the lips at rest. Once short face syndrome had been identified, the individuals
were classified into three severity subtypes: mild, moderate, and severe. The
sample was then stratified by ethnic background as White (Caucasoid), Black
(African descent), Brown (mixed Caucasian-African descent), Yellow (Asian
descent), and Brazilian Indian (Native Brazilian descent), using the Brazilian
Institute of Geography and Statistics classification. The chi-square test at the
5% significance level was used to compare frequency ratios of individuals with
vertically impaired facial relationships and across different ethnicities,
according to severity. RESULTS: The prevalence of short face pattern was 3.15%,
as 1.11%, 1.99%, and 0.02% considered mild, moderate and severe subtypes,
respectively. The severe subtype was rare (0.02%) and found only in one White
individual. The White group had the highest relative frequency (45.53%) of the
moderate subtype, followed by Brown individuals (43.40%). In the mild subtype,
Yellow (68.08%) and White (62.21%) individuals showed similar and higher relative
frequency values. CONCLUSION: The prevalence of short face pattern was 3.15%, and
White individuals had the highest prevalence.
PMID- 28400864
TI - Alveolar Bone Fracture: Pathognomonic Sign for Clinical Diagnosis.
AB - AIM: Dental injuries, especially luxation and avulsion, are common. Dental trauma
can cause alveolar bone fracture that can lead to tooth loss and malocclusion.
Single tooth alveolar bone fractures are difficult to identify unless it
protrudes through the overlying mucosa and can be visualized. Pain, malocclusion,
and tooth mobility provide signs of suspected alveolar bone fractures. Integrity
of the proximate alveolar bone should be examined for fractures where avulsion,
luxation, or other tooth trauma is detected. Any suggestion of alveolar fractures
should be further investigated with an appropriate radiograph. SUMMARY: This case
report shows a pathognomonic sign that detects and diagnosis single tooth
alveolar bone fractures, i.e., a localized hematoma crossing the attached gingiva
from the free gingival margin to the vestibular mucosa. This should serve as a
warning for localized alveolar bone fracture. A visualized hematoma and gentle,
careful palpation may help detect covered fractures when the overlying mucosa is
not perforated.
PMID- 28400865
TI - Bond Strength of Repaired Acrylic Denture Teeth Using Visible Light Cure
Composite Resin.
AB - BACKGROUND: Although bonding to denture teeth after surface treatment with
chemical agents is desirable, there is little information on the use of Visible
Light Cure composite resin (VLC) as bonding denture materials. OBJECTIVES: To
determine the effect of various surface treatments on shear bond strength between
Visible Light Cure composite resin and the acrylic denture teeth interface.
METHODS: Forty cylindrical sticks of acrylic resin with denture teeth mounted
atop were prepared. Various treatments were implemented upon the acrylic resin
teeth surfaces. The samples were divided into four groups (n = 10). Light-cured
composite resin (LC) was applied over all treated and untreated surfaces of
tested groups. The shear bond was tested using a universal tensile testing
apparatus with the knife-edge of a 0.8mm shear tester. Data were statistically
analyzed using one-way ANOVA performed at a confidence level of 95% and
significant P-value of (P <= 0.05). RESULTS: Analysis of variance (ANOVA) showed
statistically significant difference (P < 0.05) between treated and untreated
teeth surfaces. The treated surfaces exhibited various levels of bond strength
depending on the type of treatment. CONCLUSION: Application of VLC bonding agent
with prior treatment of methylmethacrylate (MMA) on the acrylic resin denture
teeth resulted in maximum bond strength with composite resin.
PMID- 28400866
TI - Association of ERAP1, IL23R and PTGER4 Polymorphisms with Radiographic Severity
of Ankylosing Spondylitis.
AB - BACKGROUND: Radiographic severity of ankylosing spondylitis (AS) shows such great
variance that some patients never develop syndesmophytes throughout the entire
disease span, whereas some develop bamboo spine relatively early. OBJECTIVE: To
study the association between ERAP1, IL23R and PTGER4 single nucleotide
polymorphisms (SNPs) and radiographic severity in AS patients. METHODS: rs27044
and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were
genotyped in 235 AS patients fulfilling the modified New York criteria. Patients
were classified as mild- and severe-AS according to modified Stoke AS spinal
score (mSASSS). Mild-AS is defined as having mSASSS of "0" following at least 10
years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients
with mild vertebral changes (i.e. squaring or erosions) were omitted for clear
stratification) regardless of disease duration. RESULTS: The genotype
distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R
rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0,
55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5+/-17.8, 73.4%
HLA-B27 positive). After adjustment for clinical differences between groups
(gender, disease duration, HLA-B27 and smoking status) by logistic regression
analysis, none of the alleles in the investigated SNPs were found to be
associated with radiographic severity of AS. CONCLUSION: In radiographically well
categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4
rs10440635 SNPs are not found to be associated with radiographic severity of AS.
PMID- 28400867
TI - Evaluation of Autoantibodies in Patients with Primary and Secondary Sjogren's
Syndrome.
AB - BACKGROUND: Antibodies to salivary gland protein 1 (SP1), carbonic anhydrase 6
(CA6) and parotid secretory protein (PSP) were discovered in an animal model of
Sjogren's syndrome (SS). Their expression was noted in patients with SS,
especially those with lower focus scores on lip biopsies and those with early
disease lacking antibodies to Ro and La. OBJECTIVE: The current studies evaluated
these autoantibodies in patients with long-standing SS expressing high levels of
anti-Ro antibodies and in patients with Sjogren's syndrome secondary to systemic
lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue
disease (MCTD). METHOD: Sera were obtained from patients and evaluated by ELISA
for IgG, IgA and IgM antibodies to SP1, CA6 and PSP. RESULTS: IgA anti-CA6
antibodies were noted in 38% of these patients, but anti-SP1, CA6 and PSP IgM or
IgG antibodies were identified only in a minority of patients. In patients with
secondary SS, antibodies to SP1/CA6/PSP were more sensitive and specific than
anti-Ro . CONCLUSION: While more studies are needed, antibodies to SP1, CA6 and
PSP provide valuable markers for the diagnosis of primary and secondary SS,
especially early in the course of the disease.
PMID- 28400868
TI - Use of Saline as a Placebo in Intra-articular Injections in Osteoarthritis:
Potential Contributions to Nociceptive Pain Relief.
AB - BACKGROUND: Osteoarthritis of the knee (OAK) is a severe debilitating condition
characterized by joint pain, stiffness, and resultant limited mobility. In recent
years, intra-articular (IA) injections have been used to relieve symptoms and
have succeeded to varying degrees either with sodium hyaluronate preparations or
with a biologic. OBJECTIVE: The objective of this review is to evaluate multiple
studies that demonstrate some relief from the symptoms of OAK in the saline arm
of various clinical trials. METHOD: A thorough literature search (PubMed) was
performed assessing the pain efficacy of various compounds compared to saline
injections in clinical trials. A total of 73 studies were identified in the
literature search including a total of 5,816 patients. These clinical trials all
involved the IA injection of a viscosupplement (hyaluronate, platelet rich plasma
(PRP), etc.) or a biologic (the low molecular weight fraction (< 5kDa) of human
serum albumin (LMWF-5A)). For all of these studies, the control arm was injection
of sterile physiological saline that approximates the salt concentration and
total solute concentration of blood and most tissues. RESULTS: Based on our
review of the current literature, the tested compounds performed with mixed
results when compared to saline injections. Moreover, OAK is a variable disease,
with severity measured on the Kellgren and Lawrence (KL) scale where various
hyaluronate preparations have a therapeutic effect mostly on KL 2-3 patients
while a biologic works best on KL 3-4 patients. CONCLUSION: Since the effect of
saline injection is always greater than no treatment, the evaluations of these
treatments can be confounded in clinical trials. Therefore, the question of
whether there are known therapeutic effects of saline injections might explain
these results.
PMID- 28400869
TI - Serum Cytokine Profile in Asian Indian Patients with Takayasu Arteritis and its
Association with Disease Activity.
AB - BACKGROUND: Arterial inflammation Takayasu arteritis (TA) is an outcome of
balance between pro- and anti-inflammatory cytokines. Comprehensive assessment of
these cytokines is important for understanding pathogenesis and assessing disease
activity. OBJECTIVE: To study pro- and anti-inflammatory cytokines representing
different T-helper cell pathway in serum samples of Asian Indian patients with TA
and to assess their association with disease activity. METHODS: Consecutive
Indian patients with TA were assayed for serum interferon-gamma, interleukin-6,
interleukin-23, interleukin-17, interleukin-10 and transforming growth factor-
beta levels at baseline and follow up visit. Patients were grouped into active
and stable disease based on Indian Takyasu Arteritis clinical Activity Score
2010. Serum levels of these cytokines between active and stable disease and
between baseline and follow up visits were compared by non-parametric tests.
RESULTS: Among 32 patients enrolled, 15 were classified as active while 17 as
stable disease at baseline. IFN-gamma levels were significantly higher in active
disease than stable disease (p=0.0129) while other cytokines did not differ
significantly between 2 groups. Serum levels of none of the cytokines changed
significantly over 2 visits in both responders and non-responders. IL23 levels
positively correlate with disease duration ((r=0.999; p<0.005). Modest
correlation was observed between IFN-gamma and IL23 levels at both baseline and
follow up and between IFN-gamma and IL-6 and CRP at follow up. CONCLUSION: IFN
gamma levels are raised in active disease in TA and correlates well with other
biomarkers of disease activity and proinflammatory cytokines. There is also a
direct correlation between Il-23 levels and disease duration.
PMID- 28400870
TI - A Prospective Cohort Study of the Therapeutic Patterns, Challenges and Outcomes
of Paediatric Femoral Fractures in a Cameroonian Tertiary Center.
AB - BACKGROUND: Knowledge of the therapeutic patterns, challenges and outcomes of
treatment of paediatric femoral fractures (PFF) helps to better choose the ideal
therapeutic modality which is still controversial. However, this data is scarce
in the sub-Saharan African literature. OBJECTIVE: To determine the therapeutic
patterns, treatment challenges and outcomes of treatment of PFF in a tertiary
care centre in Cameroon. METHOD: We conducted a prospective cohort study of all
consenting consecutive cases of femoral fractures in patients younger than 16
years managed between 2011 and 2015 at the surgical unit of Yaounde University
Teaching Hospital, Cameroon. We analysed demographic data, injury
characteristics, fracture patterns, treatment details, therapeutic challenges and
outcomes of treatment at 12 months using Flynn's criteria. RESULTS: We enrolled
30 femoral fractures from 29 children with mean age was 4.2 +/- 3.3 years. The
male gender, diaphyseal locations and spiral fracture lines were predominant.
Main mechanisms of injury were accidental falls, road traffic accidents and game
injuries. Fracture management entailed 12 tractions followed by casting, 10
casting alone, four closed reductions followed by casting, two cannulated screw
fixations, one pin fixation and one external fixation. The mean duration of
consolidation was 10.3 +/- 3.9 weeks. The outcome was rated excellent in 28
cases. Limited resources precluded fluoroscopy use, proper anaesthetic
management, early rehabilitation and patient-parent satisfaction. CONCLUSION:
Conservative management of PFF yields a good outcome in our setting. However, an
improvement in surgical, radiology and anaesthetic infrastructure is needed for
optimal PFF care.
PMID- 28400871
TI - Results of Arthroscopic Ankle Arthrodesis with Fixation Using Two Parallel
Headless Compression Screws in a Heterogenic Group of Patients.
AB - BACKGROUND: As orthopedic surgeons become skilled in ankle arthroscopy technique
and evidence -based data is supporting its use, arthroscopic ankle arthrodesis
(AAA) will likely continue to increase, but stabilization methods have not been
described clearly. We present a technique for two parallel 7.3-mm headless
compression screws fixation (HCSs) for AAA in cases of ankle arthritis with
different etiology, both traumatic and non-traumatic, including neuromuscular and
inflammatory patients. MATERIALS AND METHODS: We retrospectively verified 24
consecutive patients (25 ankles) who underwent AAA between 2011 and 2015. The
average follow-up was 26 months (range 18 to 52 months). Arthrodesis was
performed in 16 patients due to posttraumatic arthritis (in 5 as a sequela of
pilon, 6 ankles, 3 tibia fractures, and 2 had arthritis due to chronic
instability after lateral ligament injury), in 4 patients due to neuromuscular
ankle joint deformities, and in 4 patients due to rheumatoid arthritis. RESULTS:
Fusion occurred in 23 joints (92%) over an average of 12 weeks (range 6 to 18
weeks). Ankle arthrodesis was not achieved in 2 joints (8%), both in post-pilon
fracture patients. The correct foot alignment was not achieved in 4 feet (16%).
None of the treated patients required hardware removal. CONCLUSION: The presented
technique was effective in achieving a high fusion rate in a variety of diseases,
decreasing intra- and post-operative hardware complications while maintaining
adequate bone stability.
PMID- 28400872
TI - Surgical Release of Severe Flexion Contracture for Oncologic Knee Arthroplasty.
AB - BACKGROUND: Severe postoperative knee contractures after arthroplasty or
megaprosthesis reconstruction occur rarely, but are devastating complications.
Management of preoperative flexion contractures is well-described, but there is a
paucity of literature for surgical treatment of postoperative contractures. A
retrospective chart review was performed for a single surgeon of cases between
1996 and 2014. RESULTS: Nine patients (5 of 66 for pediatrics; 4 of 95 for
adults) underwent surgical release for severe stiffness after implantation of
knee megaprosthesis. The total arc of motion was improved from a preoperative
mean of 34 degrees (range, 10 degrees to 70 degrees ) to a postoperative mean
89 degrees (63 degrees to 125 degrees ). The amount of extension improved by a
mean of 27 degrees (range, -3 degrees to +70 degrees ) and the amount of
flexion improved by a mean of 28 degrees (range, -10 degrees to +75 degrees ).
CONCLUSION: Surgical release of severe postoperative knee contracture is a
challenging procedure, but in most cases, the amount of extension and flexion can
be improved, yielding a greater total arc of motion.
PMID- 28400873
TI - Good Early Results Obtained with a Guided-Motion Implant for Total Knee
Arthroplasty: A Consecutive Case Series.
AB - BACKGROUND: Previous studies have shown a high incidence of complications with a
bi-cruciate stabilized (BCS) guided-motion total knee arthroplasty (TKA) design,
which led to recent modifications of the design by the manufacturer. OBJECTIVE:
The current study was undertaken to assess whether the use of this TKA system
with an extension-first surgical technique is associated with a similar rate of
short-term adverse outcome as reported in literature. MATERIAL AND METHODS: This
retrospective study enrolled 257 consecutive patients (257 knees) undergoing TKA
for osteoarthritis of the knee, with the first 153 receiving cemented Journey BCS
I implants and the remaining 104 receiving cemented Journey BCS II implants when
these became available. RESULTS: Mean follow-up time for the cohort was 24.5 +/-
7.8 months (range, 12 - 36 months). There were no cases of stiffness. Incidence
of iliotibial friction syndrome was considered low: three (2.0%) knees in the BCS
I group and two (1.9%) in the BCS II group (p = 0.676). Five (2.5%) knees
presented with mild instability in midflexion, three (2.0%) in the BCS I group
and two (1.9%) in the BCS II group (p = 0.676). One patient with a BCS I implant
required reoperation for aseptic loosening 23 months postoperatively. At one-year
follow-up, there were no clinically relevant differences in any of the clinical
outcomes. CONCLUSION: When used in combination with an extension-first surgical
technique, good early functional results with an acceptable rate of complications
were obtained with both the original and the updated Journey BCS knee implant.
PMID- 28400874
TI - Locking versus Non-locking Neutralization Plates with Limited Excision and
Internal Fixation for Treatment of Extra-articular Type a Distal Tibial
Fractures.
AB - PURPOSE: This study aimed to compare the clinical, radiologic, and cost
effectiveness results between locking and non-locking plates for the treatment of
extra-articular type A distal tibial fractures. METHODS: We performed a
retrospective review of AO/OTA 42-A1, A2 distal tibial fractures treated by
plates from January 2011 to June 2013. Patients were divided to the locking plate
group or the non-locking plate group. Clinical outcomes, radiographic outcomes,
and hospitalization fee were compared between the two plates groups. RESULTS: 28
patients were treated with a locking plate and 23 patients were treated with a
non-locking plate. The mean follow-up was 18.8 months (12-23 months). There were
no significant differences between the groups in surgical time, bleeding, bone
union time, or AOFAS scores. The cost of the locking plate was Y24,648.41 +/-
6,812.95 and the cost of the non-locking plate was Y11,642 +/- 3,162.57, p <
0.001. Each group had one patient that experienced superficial infection these
wounds were readily healed by oral antibiotics and dressing changes. To date,
five patients in the locking group and ten patients in the non-locking group had
sensations of metal stimulation or other discomfort (X2 = 3.99, p < 0.05) Until
the last follow-up, 14 patients in the locking plate group and 18 patients in the
non-locking plate group had their plates removed or wanted to remove their plates
(X2 = 4.31, p < 0.05). CONCLUSION: The use of locking or non-locking plates
provides a similar outcome in the treatment of distal fractures. However the
locking plate is much more expensive than the non-locking plate.
PMID- 28400875
TI - Editorial Letter for Thematic Issue on Shoulder Pathology.
PMID- 28400876
TI - Adhesive Capsulitis of the Shoulder. Is there Consensus Regarding the Treatment?
A Comprehensive Review.
AB - BACKGROUND: Adhesive capsulitis of the shoulder (ACS) is a common self-limiting
condition characterized by disabling pain and restricted movements. Its
pathophysiology is poorly understood, clinically it is characterized by stages of
pain and stiffness, and finally often patients never recover fully. However,
there is no consensus about available methods of treatment for ACS. The aims of
this paper are to discuss and develop issues regarding approaches to management
in ACS in the stages of it. METHODS: A review of the literature was performed and
guidelines for the treatment of that clinical entity for doctors and health care
professionals are provided. RESULTS: Anti-inflammatory medications, steroid
and/or hyaluronate injections and physiotherapy is the mainstay of conservative
management either alone in the first stages or in combination with other
treatment modalities in the later stages. Next line of treatment, involving minor
to moderate intervention, includes suprascapular nerve block, distension
arthrography and manipulation under anaesthesia. In order to avoid complications
of "blind intervention", arthroscopic capsular release is gradually more commonly
applied, and in recalcitrant severe cases open release is a useful option.
CONCLUSION: Various modalities of conservative management and gradually more
surgical release are applied. However, often clinicians choose on personal
experience and training rather than on published evidence.
PMID- 28400877
TI - Latissimus Dorsi Transfer in Posterior Irreparable Rotator Cuff Tears.
AB - BACKGROUND: Massive rotator cuff tears pose a difficult and complex challenge
even for the experienced surgeon; inability to repair these tears by conventional
means designates them as irreparable, while management becomes quite taxing.
Several operative options have been suggested for the management of such lesions
with varying degrees of success, while it is imperative to match patient demands
and expectations to the predicted outcome. METHODS: Research articles are
examined and key concepts are discussed, in order to provide an evidence based
review of the available literature. The anatomy and pathomechanics along with the
indications, contraindications and surgical techniques are reported. RESULTS:
Transfer of the Latissimus dorsi has been used with success to restore shoulder
function in deficits of the posterior rotator cuff. Although it can be used in a
variety of settings, the ideal patient for a Latissimus dorsi tendon transfer is
a young and active individual, with no glenohumeral osteoarthritis that has a
severe disability and weakness related to an irreparable posterior cuff tear.
CONCLUSION: Tendon transfers have proved to be a successful treatment option in
salvaging this difficult problem, providing pain relief and restoring shoulder
function. Despite the excellent functional outcomes and pain suppression
following operation, a variety of factors may affect the outcome; thus making
indications and preoperative assessment a valuable component.
PMID- 28400878
TI - The Impact of Re-tear on the Clinical Outcome after Rotator Cuff Repair Using
Open or Arthroscopic Techniques - A Systematic Review.
AB - BACKGROUND: It is generally accepted that rotator cuff repair gives satisfactory
results in the long term, although most studies have so far shown a fairly high
rate of structural failure or re-tear. The purpose of this review study is to
assess whether failure of the repaired cuff to heal could negatively affect the
functional outcome. METHODS: This article includes an extensive Internet PubMed
based research in the current English-language literature including level I to
level V studies as well as systematic reviews. RESULTS: According to this
extended study research, the results are mixed; certain reports show that
patients with a healed rotator cuff repair have improved function and strength
compared to those with structural failure, whereas other studies support the
generally perceived concept that tendon re-tear does not lead to inferior
clinical outcome. CONCLUSION: Further high-level prospective studies with larger
numbers of patients and longer follow up are needed to overcome the current
debate over function between healed and failed rotator cuff repairs.
PMID- 28400879
TI - Reverse Shoulder Arthroplasty for the Treatment of 3 and 4- Part Fractures of the
Humeral Head in the Elderly.
AB - BACKGROUND: Proximal humeral fractures in elderly patients present with severe
comminution and osteoporotic bone quality. Reverse shoulder arthroplasty has
lately been proven beneficial in treating patients with complex proximal humeral
fractures. The above technique is recommended and has better results in elderly
than in younger individuals. METHODS: We performed a literature search in the
databases Pubmed, Medline, EMBASE and Cochrane Library for published articles
between 1970 and 2016 using the terms: proximal humerus fractures and reverse
shoulder arthroplasty. RESULTS: Significant benefits with the use of reverse
prosthesis, especially in patients older than 70 years with a proximal humeral
fracture, include reduced rehabilitation time as well as conservation of a fixed
fulcrum for deltoid action in case of rotator cuff failure. Compared with
hemiarthroplasty and internal fixation, reverse prosthesis may be particularly
useful and give superior outcomes in older patients, due to comminuted fractures
in osteopenic bones. However, significant disadvantages of this technique are
potential complications and a demanding learning curve.Therefore, trained
surgeons should follow specific indications when applying the particular
treatment of proximal humeral fractures and be familiar with the surgical
technique. CONCLUSION: Although long-term results and randomized studies for
reverse prosthesis are lacking, short and mid- term outcomes have given promising
results encouraging more shoulder surgeons to use this type of prosthesis in
proximal humeral fractures.
PMID- 28400880
TI - Arthroscopic Findings in Anterior Shoulder Instability.
AB - BACKGROUND: In the last years, basic research and arthroscopic surgery, have
improved our understanding of shoulder anatomy and pathology. It is a fact that
arthroscopic treatment of shoulder instability has evolved considerably over the
past decades. The aim of this paper is to present the variety of pathologies that
should be identified and treated during shoulder arthroscopy when dealing with
anterior shoulder instability cases. METHODS: A review of the current literature
regarding arthroscopic shoulder anatomy, anatomic variants, and arthroscopic
findings in anterior shoulder instability, is presented. In addition, correlation
of arthroscopic findings with physical examination and advanced imaging (CT and
MRI) in order to improve our understanding in anterior shoulder instability
pathology is discussed. RESULTS: Shoulder instability represents a broad spectrum
of disease and a thorough understanding of the pathoanatomy is the key for a
successful treatment of the unstable shoulder. Patients can have a variety of
pathologies concomitant with a traditional Bankart lesion, such as injuries of
the glenoid (bony Bankart), injuries of the glenoid labrum, superiorly (SLAP) or
anteroinferiorly (e.g. anterior labroligamentous periosteal sleeve avulsion, and
Perthes), capsular lesions (humeral avulsion of the glenohumeral ligament), and
accompanying osseous-cartilage lesions (Hill-Sachs, glenolabral articular
disruption). Shoulder arthroscopy allows for a detailed visualization and a
dynamic examination of all anatomic structures, identification of pathologic
findings, and treatment of all concomitant lesions. CONCLUSION: Surgeons must be
well prepared and understanding the normal anatomy of the glenohumeral joint,
including its anatomic variants to seek for the possible pathologic lesions in
anterior shoulder instability during shoulder arthroscopy. Patient selection
criteria, improved surgical techniques, and implants available have contributed
to the enhancement of clinical and functional outcomes to the point that
arthroscopic treatment is considered nowadays the standard of care.
PMID- 28400881
TI - Long Term Outcomes of Arthroscopic Shoulder Instability Surgery.
AB - BACKGROUND: Anterior shoulder instability has been successfully managed
arthroscopically over the past two decades with refined "anatomic" reconstruction
procedures involving the use of anchors for the repositioning and re-tensioning
of the antero-inferior capsuloligamentous complex, in an effort to recreate its
"bumper effect". METHODS: Research and online content related to arthroscopic
treatment of shoulder instability was reviewed and their results compared.
RESULTS: The short- and mid-term results of this technique have been very
satisfactory. The greatest number of recent reports suggests that long-term
results (>5 years follow-up) remain rather satisfactory, especially in the
absence of significant glenoid bone loss (>20-25%). In these studies recurrent
instability, in the form of either dislocation or subluxation, ranges from 5.1 to
over 20%, clinical scores, more than 5 years after the index procedure, remain
good or excellent in >80% of patient population as do patient satisfaction and
return to previous level of activities. As regards arthroscopic non-anatomic bony
procedures (Latarjet or Bristow procedures) performed in revision cases or in the
presence of >20-25% bone loss of the anteroinferior aspect of the glenoid, recent
reports suggest that their long-term results are very satisfactory both in terms
of re-dislocation rates and patient satisfaction. CONCLUSION: It appears that
even "lege artis" performance of arthroscopic reconstruction decelerates but does
not obliterate the degenerative procedure of dislocation arthropathy. The
presence and grade of arthritic changes correlate with the number of dislocations
sustained prior to the arthroscopic intervention, the number of anchors used and
the age at initial dislocation and surgery. However, the clinical significance of
radiologically evident dislocation arthropathy is debatable.
PMID- 28400882
TI - Suprascapular Nerve Pathology: A Review of the Literature.
AB - BACKGROUND: Suprascapular nerve pathology is a rare diagnosis that is
increasingly gaining popularity among the conditions that cause shoulder pain and
dysfunction. The suprascapular nerve passes through several osseoligamentous
structures and can be compressed in several locations. METHODS: A thorough
literature search was performed using online available databases in order to
carefully define the pathophysiology and to guide diagnosis and treatment.
RESULTS: Suprascapular neuropathy diagnosis is based on a careful history and a
thorough clinical and radiological examination. Although the incidence and
prevalence of the condition remain unknown, it is highly diagnosed in specific
groups (overhead athletes, patients with a massive rotator cuff tear) probably
due to higher interest. The location and the etiology of the compression are
those that define the treatment modality. CONCLUSION: Suprascapular neuropathy
diagnosis is based on a careful history and a thorough clinical and radiological
examination. The purpose of this article is to describe the anatomy of the
suprascapular nerve, to define the pathophysiology of suprascapular neuropathy
and to present methodically the current diagnostic and treatment strategies.
PMID- 28400883
TI - Rehabilitation after Rotator Cuff Repair.
AB - BACKGROUND: Rotator cuff tears are a very common condition that is often
incapacitating. Whether non-surgical or surgical, successful management of
rotator cuff disease is dependent on appropriate rehabilitation. If conservative
management is insufficient, surgical repair is often indicated. Postsurgical
outcomes for patients having had rotator cuff repair can be quite good. A
successful outcome is much dependent on surgical technique as it is on
rehabilitation. Numerous rehabilitation protocols for the management of rotator
cuff disease are based primarily on clinical experience and expert opinion. This
article describes the different rehabilitation protocols that aim to protect the
repair in the immediate postoperative period, minimize postoperative stiffness
and muscle atrophy. METHODS: A review of currently available literature on
rehabilitation after arthroscopic rotator cuff tear repair was performed to
illustrate the available evidence behind various postoperative treatment
modalities. RESULTS: There were no statistically significant differences between
a conservative and an accelerated rehabilitation protocol . Early passive range
of motion (ROM) following arthroscopic cuff repair is thought to decrease
postoperative stiffness and improve functionality. However, early aggressive
rehabilitation may compromise repair integrity. CONCLUSION: The currently
available literature did not identify any significant differences in functional
outcomes and relative risks of re-tears between delayed and early motion in
patients undergoing arthroscopic rotator cuff repairs. A gentle rehabilitation
protocol with limits in range of motion and exercise times after arthroscopic
rotator cuff repair would be better for tendon healing without taking any
substantial risks. A close communication between the surgeon, the patient and the
physical therapy team is important and should continue throughout the whole
recovery process.
PMID- 28400885
TI - The "Purse-string" Technique for Shoulder Stabilization, Description of the
Technique, Long term Results and Literature Review.
AB - BACKGROUND: Over the last 2 decades arthroscopic stabilization and Bankart repair
has gained popularity due to the advances in materials and surgical techniques.
Results of arthroscopic stabilization have been similar to open without the risks
of it. The number of anchors used has been suggested to be very important in
"spot-weld" arthroscopic stabilization however the "purse-string" technique (PST)
can achieve similar results using only one anchor. We describe technique and long
term results from using the PST and search the literature for other papers
regarding PST. METHODS: Between 2003 and 2013 a total of 193 patients were
operated. Patients included those with anterior instability. Using PubMed
relevant studies reporting results of PST were identified. RESULTS: Mean follow
up was 2 (range 0.5 to 3) years. 9 (4.7%) patients experienced recurrent
instability. Almost all patients (97%) returned to their sporting and leisure
activities and all professional athletes went back to the same sport. One more UK
centre reported 6.1% recurrence in 114 patients at 4 years follow up. These
results are similar to the published 11% recurrence of instability after "spot
weld" arthroscopic techniques at 11 years clinical follow-up. CONCLUSION: This
study indicates that PST is safe and effective alternative method for the
treatment of anterior shoulder instability. In this technique with one anchor
simultaneous repair of labrum, creation of an anterior bumper and capsular shift
can be achieved. It has the advantage of being cheaper, faster yet efficient with
good long term results and leaves space for revision anchors in case of
recurrence.
PMID- 28400886
TI - Corneal Toxicity Following Exposure to Asclepias Tuberosa.
AB - PURPOSE: To present a case of corneal toxicity following exposure to milky plant
latex from Asclepias tuberosa. METHODS: A 70-year-old female presented with
blurred vision and pain in her left eye after handling an Ascepias tuberosa.
Clinical examination revealed a corneal stromal oedema with small epithelial
defects. The corneal endothelium was intact and folds in Descemets membrane were
observed. The oedema was treated with chloramphenicol, dexamethasone and
scopolamine. RESULTS: The corneal oedema had appeared after corneal exposure to
the plant, Asclepias tuberosa, whose latex contains cardenolides that inhibit the
Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours.
After nine months the best corrected visual acuity was 20/20. CONCLUSION: Corneal
toxicity has previously been reported for plants of the Asclepias family. This is
a rare case describing severe corneal toxicity caused by exposure to latex from
Asclepias tuberosa. Handling of plants of the Asclepias family should be kept as
a differential diagnosis in cases of acute corneal toxicity.
PMID- 28400887
TI - Antibiotic Prophylaxis in Orbital Fractures.
AB - PURPOSE: To determine whether prophylactic antibiotic use in patients with
orbital fracture prevent orbital infection. DESIGN: Retrospective cohort study.
PARTICIPANTS: All patients diagnosed with orbital fracture between January 1,
2008 and March 1, 2014 at The George Washington University Hospital and Clinics.
MAIN OUTCOME MEASURES: Development of orbital infection. RESULTS: One hundred
seventy-two patients with orbital fracture met our inclusion and exclusion
criteria. No orbital infections were documented. Twenty subjects (12%) received
no prophylactic antibiotic, and two (1%) received only one dose of antibiotics
pre-operatively for surgery. For primary antibiotic, 136 subjects (79%) received
oral antibiotics, and 14 (8%) received intravenous (IV) antibiotics (excluding
cefazolin). Cephalexin and amoxicillin-clavulanate were the most prescribed oral
antibiotics that are equally effective. Five-to-seven day courses of antibiotics
had no increased infections compared to ten-to-fourteen day courses. Calculated
boundaries for effectiveness of prophylactic antibiotics ranged from a Number
Needed to Treat (NNT) of 75 to a Number Needed to Harm (NNH) of 198. CONCLUSION:
Antibiotics for prevention of orbital infection in patients with orbital
fractures have become widely used. Coordination between trauma teams and
specialists is needed to prevent patient overmedication and antibiotic
resistance. Should antibiotics be used, shorter courses and avoidance of broad
spectrum agents are recommended. Additional studies are needed.
PMID- 28400884
TI - Effectiveness of Biologic Factors in Shoulder Disorders.
AB - BACKGROUND: Shoulder pathology can cause significant pain, discomfort, and loss
of function that all interfere with activities of daily living and may lead to
poor quality of life. Primary osteoarthritis and rotator cuff diseases with its
sequalae are the main culprits. Management of shoulder disorders using biological
factors gained an increasing interest over the last years. This interest reveals
the need of effective treatments for shoulder degenerative disorders, and
highlights the importance of a comprehensive and detailed understanding of the
rapidly increasing knowledge in the field. METHODS: This study will describe most
of the available biology-based strategies that have been recently developed,
focusing on their effectiveness in animal and clinical studies. RESULTS: Data
from in vitro work will also be briefly presented; in order to further elucidate
newly acquired knowledge regarding mechanisms of tissue degeneration and repair
that would probably drive translational work in the next decade. The role of
platelet rich-plasma, growth factors, stem cells and other alternative treatments
will be described in an evidence-based approach, in an attempt to provide
guidelines for their clinical application. Finally, certain challenges that
biologic treatments face today will be described as an initiative for future
strategies. CONCLUSION: The application of different growth factors and
mesenchymal stem cells appears as promising approaches for enhancing biologic
repair. However, data from clinical studies are still limited, and future studies
need to improve understanding of the repair process in cellular and molecular
level and evaluate the effectiveness of biologic factors in the management of
shoulder disorders.
PMID- 28400888
TI - Macular Evaluation with Spectral Domain Type Optic Coherence Tomography in Eyes
with Acute Nonarteritic Ischemic Optic Neuropathy at the Presentation Visit.
AB - PURPOSE: To evaluate the macula with spectral domain type optic coherence
tomography (OCT) in eyes with acute nonarteritic anterior ischemic optic
neuropathy (NAION) at the presentation visit. METHODS: Medical charts of the 133
patients who received the diagnosis of acute NAION between January 2008 and July
2014 at the Neuro-ophthalmology unit of Dokuz Eylul University were reviewed
retrospectively. Sixtythree patients within 30 days of symptom onset with
available baseline spectral domain type macular OCT were included in this study.
Clinical and macular characteristics of the affected eye were assessed and
compared to the fellow eyes. RESULTS: Sixty-three eyes of 63 patients comprised
the study group. Twenty one study eyes (33.3%) had normal posterior pole, 22
(34.9%) some evidence of subretinal fluid, 10 (15.8%) vitreomacular adhesion,
five (7%) age-related macular degeneration related changes, four (6%) epiretinal
membrane and one (1%) previous grid laser scars. On the other hand, 41 of 63 the
fellow eyes (65%) had normal posterior pole, ten (15.8%), vitreomacular adhesion,
seven (10.7%), age-related macular degeneration related changes, three (4%)
epiretinal membrane and two (3%) other type of changes. OCT scan passing through
the fovea exhibited 10 or more hyperreflective dots in 10 (15%) of the study eyes
whereas two of the fellow eyes (3.2%) had 10 or more hyperreflective dots.
CONCLUSION: Macular OCT can be a part of the routine neuroophthalmologic
examination in patients with acute NAION not only to show the NAION related
changes such as the subretinal fluid accumulation but also to identify the other
coexistent macular abnormalities.
PMID- 28400889
TI - Evaluation of Ocular Surface Disease in Asian Patients with Primary Angle
Closure.
AB - OBJECTIVE: To evaluate the incidence of ocular surface disease (OSD) and to
determine the effects of topical pressure-lowering drugs on ocular surface
disease in primary angle closure patients. METHODS: This was a cross-sectional
comparative study comparing primary angle closure glaucoma (PACG) patients (Group
A) with primary angle closure and primary angle closure suspect (Group B). Group
A was treated with topical pressure-lowering drugs; Group B was not. Data on
ocular diagnosis and details of treatment were obtained from medical records.
Ocular surface disease incidence was assessed using the Ocular Surface Disease
Index (OSDI) questionnaire and from clinical signs using Schirmer's test, tear
break-up time and corneal fluorescein stain. Predictive Analytic Software 20 and
STATA analysis software were used for statistical analyses. RESULTS: Group A
demonstrated a higher rate of OSD (OSDI 52.3%, Schirmer's test 70.5%, tear break
up time (TBUT) 75%, corneal staining 77.3%) compared to Group B (OSDI 39.0%,
Schirmer's test 73.2%, TBUT 58.5% and cornea staining 14.6%) except for
Schirmer's test. There was a significant difference in mean score of OSDI
(p=0.004), TBUT (p=0.008) and cornea staining (p<0.001) between two groups.
Primary angle closure glaucoma treated with more than two medications and for
more than three years had worse ocular surface disease parameters but without
statistical significant difference. CONCLUSION: Ocular surface disease is common
in PACG patients treated with topical pressure-lowering drugs. Topical pressure
lowering drugs caused significant OSD symptoms and signs except for tear
production in PACG patients. Thorough evaluation of ocular surface disease is
important to ensure appropriate treatment and intervention in PACG patients.
PMID- 28400890
TI - Comparison of Ethnic-specific Databases in Heidelberg Retina Tomography-3 to
Discriminate Between Early Glaucoma and Normal Chinese Eyes.
AB - PURPOSE: To compare the diagnostic accuracy of the 3 race-specific normative
databases in Heidelberg Retina Tomography (HRT)-3, in differentiating between
early glaucomatous and healthy normal Chinese eyes. METHOD: 52 healthy volunteers
and 25 glaucoma patients were recruited for this prospective cross-sectional
study. All underwent standardized interviews, ophthalmic examination, perimetry
and HRT optic disc imaging. Area under the curve (AUC) receiver operating
characteristics, sensitivity and specificity were derived to assess the
discriminating abilities of the 3 normative databases, for both Moorfields
Regression Analysis (MRA) and Glaucoma Probability Score (GPS). RESULTS: A
significantly higher percentage (65%) of patients were classified as "within
normal limits" using the MRA-Indian database, as compared to the MRA-Caucasian
and MRA-African-American databases. However, for GPS, this was observed using the
African-American database. For MRA, the highest sensitivity was obtained with
both Caucasian and African-American databases (68%), while the highest
specificity was from the Indian database (94%). The AUC for discrimination
between glaucomatous and normal eyes by MRA-Caucasian, MRA-African-American and
MRA-Indian databases were 0.77 (95% CI, 0.67-0.88), 0.79 (0.69-0.89) and 0.73
(0.63-0.84) respectively. For GPS, the highest sensitivity was obtained using
either Caucasian or Indian databases (68%). The highest specificity was seen with
the African-American database (98%). The AUC for GPS-Caucasian, GPS-African
American and GPS-Indian databases were 0.76 (95% CI, 0.66-0.87), 0.77 (0.67-0.87)
and 0.76 (0.66-0.87) respectively. CONCLUSION: Comparison of the 3 ethnic
databases did not reveal significant differences to differentiate early
glaucomatous from normal Chinese eyes.
PMID- 28400891
TI - Family Health Conversations have Positive Outcomes on Families - A Mixed Method
Research Study.
AB - BACKGROUND: Having a family member living in a residential home affects the
entire family and can be hard to handle. Family members require encouraging and
open communication support from nurses during and after relocation to a
residential home. A Family Systems Nursing intervention, "Family Health
Conversations" (FamHC) was conducted in order to strengthen the health of
families having relatives at residential home for older people. OBJECTIVES: The
aims of this study were to evaluate the responses to the Family Health
Conversations in families with a member living at a residential home for older
people and to integrate the empirical results with a theoretical assumption upon
which the intervention was based. METHODS: A mixed methods research design was
used. The Swedish Health-Related Quality of Life Survey and the Family Hardiness
Index were administered before and 6 months after the intervention. Qualitative
data was collected by semi-structured interviews with each family 6 months post
intervention. The sample included 10 families comprising 22 family members.
RESULT: Main finding was that FamHCs helped family members process their feelings
about having a member living at a residential home and made it easier for them to
deal with their own situations. FamHCs helped to ease their consciences, improve
their emotional well-being, and change their beliefs about their own
insufficiency and guilt. Seeing problems from a different perspective facilitated
the families' thinking in a new way. CONCLUSION: These findings showed that FamHC
could be an important type of intervention to improve family functioning and
enhance the emotional well-being.
PMID- 28400892
TI - Use of Social Media By Nurse Educator Students: An Exploratory Survey.
AB - BACKGROUND: Information and Communication Technology (ICT) opens up new
possibilities for introducing innovative teaching and learning methods to deliver
education in different educational areas. Use of internet and social media has
grown rapidly and is a key way in how nurses and nurse educator students find
information. However, the evidence is still lacking how nurse educator students
use social media. OBJECTIVE: The aim of this study is to describe nurse educator
students' use of social media and the ways in which their educational needs are
related to social media. METHOD: The data were collected using a structured
questionnaire that included one open question. Altogether, 49 nurse educator
students completed and returned the questionnaire (response rate 96%). The
quantitative data were analysed using statistical programme SPPS and content
analysis. RESULTS: While many nurse educator students reported using the tools of
social media, others claimed that they do not use social media at all. Facebook
was most common (53% use it every day) and YouTube (17%) the second most common
form of social media used to support daily living. The participants reported
using YouTube (6% use it every day) and Facebook (4%) most often as support in
their studies. They reported using Second life as virtual reality form of social
media, the least. The most common educational needs of nurse educator students
include receiving more in-depth information about how to use social media, as
well as more practice in using it. CONCLUSION: In the future, the education of
the nurse educator students should include even more in-depth information about
the forms of social media and about the advantages of using it in teaching. The
education should encourage nurse educator students and provide them with more
possibilities to train and make use of the benefits of social media as support in
their daily lives and studies. There is need for more robust evidence of social
media use in nurse educator students education.
PMID- 28400893
TI - Epidermolysis bullosa simplex with muscular dystrophy. Review of the literature
and a case report.
AB - BACKGROUND: Epidermolysis bullosa simplex associated with muscular dystrophy is a
genetic skin disease caused by plectin deficiency. A case of a 19-year-old Czech
patient affected with this disease and a review all previously published clinical
cases are presented. MAIN OBSERVATIONS: In our patient, skin signs of the disease
developed after birth. Bilateral ptosis at the age of 8 years was considered as
the first specific symptom of muscular dystrophy. Since then, severe scoliosis,
urological and psychiatric complication have quickly developed. The signs of
plectin deficiency were found by histopathological studies, electron microscopy
and antigen mapping of the skin and muscular samples. Two autosomal recessive
mutations in the plectin gene leading to premature termination codon were
disclosed by mutation analysis. By review of all published clinical cases, 49
patients with this disease were found. 54 different mutations in the plectin gene
were published, p.(Arg2319*) in exon 31 being the most frequently found. Median
age of muscular dystrophy development was 9.5 years. Hoarseness and respiratory
complications were the most often complications beside skin involvement.
CONCLUSION: Epidermolysis bullosa simplex with muscular dystrophy was diagnosed
based on clinical, histopathological (skin and muscle biopsy) and mutation
analysis of the plectin gene. Overview of the genetic and clinical characteristic
of this disease could be presented by review of all previously published clinical
cases.
PMID- 28400894
TI - Surgical suturing-induced melanocytic nevi. A new type of eruptive melanocytic
nevi?
AB - BACKGROUND: Nevogenesis is a complex process involving several pathogenetic
mechanisms, including genetic factors, hormonal influences and UV-radiation.
Trauma has been described as a triggering factor for an alternative pathway of
nevogenesis. Eruptive melanocytic nevi (EMN), related either to immunosuppression
or to blistering disorders, represent a special type of nevi probably induced by
the disruption of the dermo-epidermal junction and consequent proliferation of
quiescent pigment cells during re-epithelization. MAIN OBSERVATIONS: We report
two patients with three melanocytic nevi that developed de novo along the
direction of surgical suturing, following surgical operation for other reason.
The lesions exhibited special dermoscopic characteristics and histology revealed
features of acquired melanocytic nevi. CONCLUSIONS: Such cases may represent a
new type of eruptive nevus, the surgical suturing-induced nevus, which should be
included in the differential diagnosis of new pigmentation developing within a
scar.
PMID- 28400895
TI - Melanoma and basal cell carcinoma in the hereditary leiomyomatosis and renal cell
cancer syndrome. An expansion of the oncologic spectrum.
AB - BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is
an autosomal dominant syndrome due to mutation in fumarate hydratase. Patients
with HLRCC frequently develop cutaneous and uterine leiomyomata and are at risk
for renal cell carcinoma. Rarely, other malignancies have been reported. MAIN
OBSERVATIONS: We report the development of basal cell carcinoma and melanoma in
two siblings with genetically-confirmed HLRCC. CONCLUSIONS: It is unclear whether
the development of melanoma and basal cell carcinoma in our patients is due
directly to their mutations in the gene encoding fumarate hydratase, or genetic
susceptibility at another unrelated locus, or whether these are incidental
lesions. However this observation has implications for careful and routine skin
surveillance in patients with HLRCC for lesions other than cutaneous leiomyomata.
PMID- 28400896
TI - Treatment of recalcitrant erosive oral lichen planus and desquamative gingivitis
with oral apremilast.
AB - BACKGROUND: Erosive oral lichen planus and desquamative gingivitis are uncommon
but severe debilitating variants of oral lichen planus. Treatment of these
presentations is difficult and challenging. MAIN OBSERVATION: A 44-year-old woman
was referred to the dermatology clinic with chronic painful lichen planus-related
gingivitis and buccal erosions. She has failed multiple treatments including
topical clobetasol and tacrolimus, intralesional corticosteroids and several
systemic and immunosuppressive agents. Following completion of three months of
treatment with oral apremilast at a dose of 30 mg twice daily, significant
improvement was noted in her disease activity. CONCLUSION: Oral apremilast may be
a safe and effective treatment for erosive oral lichen planus.
PMID- 28400897
TI - Postsurgical Pyoderma Gangrenosum Following Carpal Tunnel Release: A Rare Disease
Following a Common Surgery.
AB - Objective: Postsurgical pyoderma gangrenosum is a rare but potentially
devastating condition for surgical patients. While pyoderma gangrenosum has 2
subtypes, typical and atypical, each can be further classified by its heralding
features. These include ulcerative, pustular, bullous, and vegetative. The
presentation can be a result of trauma or, as mentioned before, postsurgical. The
plastic and reconstructive surgeon most likely will encounter postsurgical
pyoderma gangrenosum in practice, as it has been reported in patient populations
frequently seen in plastic surgery clinics. Methods: We present a unique case of
idiopathic postsurgical pyoderma gangrenosum in a patient who presented after
carpal tunnel release, the most common surgery of the hand and wrist performed in
the United States annually. This is believed to be the first ever case reported
in the literature of pyoderma gangrenosum following carpal tunnel release.
Results: The patient's disease course was complicated by surgical debridement
prior to diagnosis. Unfortunately, this condition necessitated mid-forearm
amputation. The wound eventually healed with primary closure and appropriate
medical therapy. Conclusion: Previous experience with this disease, a high index
of suspicion, and general education regarding the disease process and its
management could potentially have prevented this outcome. We hope to underscore
that it is important to consider a patient's entire history and to have a high
index of suspicion in unusual postsurgical wounds in order to adequately
diagnose, treat, and manage patients who develop postsurgical pyoderma
gangrenosum.
PMID- 28400898
TI - Many Neurology Readmissions Are Nonpreventable.
AB - INTRODUCTION: Reducing unplanned hospital readmissions has become a national
focus due to the Centers for Medicare and Medicaid Services' (CMS) penalties for
hospitals with high rates. A first step in reducing unplanned readmission is to
understand which patients are at high risk for readmission, which readmissions
are planned, and how well planned readmissions are currently captured in
comparison to patient-level chart review. METHODS: We examined all 5455 inpatient
neurology admissions over a 2-year period to University of California San
Francisco Medical Center and Johns Hopkins Hospital via chart review. We
collected information such as patient age, procedure codes, diagnosis codes, all
payer diagnosis-related group, observed length of stay (oLOS), and expected
length of stay. We performed multivariate logistic modeling to determine
predictors of readmission. Discharge summaries were reviewed for evidence that a
subsequent readmission was planned. RESULTS: A total of 353 (6.5%) discharges
were readmitted within 30 days. Fifty-five (15.6%) of the 353 readmissions were
planned, most often for a neurosurgical procedure (41.8%) or immunotherapy
(23.6%). Only 8 of these readmissions would have been classified as planned using
current CMS methodology. Patient age (odds ratio [OR] = 1.01 for each 10-year
increase, P < .001) and estimated length of stay (OR = 1.04, P = .002) were
associated with a greater likelihood of readmission, whereas index admission oLOS
was not. CONCLUSIONS: Many neurologic readmissions are planned; however, these
are often classified by current CMS methodology as unplanned and penalized
accordingly. Modifications of the CMS lists for potentially planned neurological
and neurosurgical procedures and for acute discharge neurologic diagnoses should
be considered.
PMID- 28400899
TI - How a CT-Direct Protocol at an American Comprehensive Stroke Center Led to Door
to-Needle Times Less Than 30 Minutes.
AB - BACKGROUND AND PURPOSE: The safety and efficacy of intravenous tissue plasminogen
activator (IV tPA) following acute ischemic stroke (AIS) is dependent on its
timely administration. In 2014, our Comprehensive Stroke Center designed and
implemented a computed tomography-Direct protocol to streamline the evaluation
process of suspected patients with AIS, with the aim of reducing door-to-needle
(DTN) times. The objectives of our study were to describe the protocol
development and implementation process, and to compare DTN times and symptomatic
intracranial hemorrhage (sICH) rates before and after protocol implementation.
METHODS: Data were prospectively collected for patients with AIS receiving IV tPA
between January 1, 2010, and May 31, 2015. The DTN times, examined as median
times and time treatment windows, and sICH rates were compared pre- and
postimplementation. RESULTS: Two hundred ninety-five patients were included in
the study. After protocol implementation, median DTN times were significantly
reduced (38 vs 28 minutes; P < .001). The distribution of patients treated in the
three time treatment windows described below changed significantly, with an
increase in patients with DTN times of 30 minutes or less, and a decrease in
patients with DTN times 31 to 60 minutes and over 60 minutes (P < .001). There
were two cases of sICH prior to implementation and one sICH case
postimplementation. CONCLUSIONS: The implementation of a protocol that
streamlined the processing of suspected patients with AIS significantly reduced
DTN time without negatively impacting patient safety.
PMID- 28400900
TI - Conjugate Eye Deviation on CT Associated With Worse Outcomes Despite IV
Thrombolysis.
AB - INTRODUCTION: Rapid stroke management has significant implications in patient
outcomes. Ipsilateral computed tomography conjugate eye deviation (CT-CED) has
been associated with worse outcomes but has never been evaluated as predictive of
vascular occlusion. To test the hypothesis that CT-CED is a marker for vascular
occlusion, we evaluated patients treated with intravenous tissue plasminogen
activator (IV tPA). METHODS: We performed a retrospective analysis of patients
with acute ischemic stroke treated with IV tPA at a large tertiary care hospital
over an 18-month period. A waiver of informed consent was granted. Two examiners
evaluated baseline brain CTs blinded to the location of infarct to assess the
presence of CT-CED and follow-up imaging for the location of infarct and the
presence of intracranial large vessel occlusion. Demographics, initial National
Institutes of Health Stroke Scale (NIHSS), modified Rankin Scales (mRSs), and
hospital length of stay (LOS) were collected. RESULTS: Among 104 patients treated
with IV tPA, 36 had CT-CED. Inter-rater reliability for CT-CED was excellent
(kappa = 0.97; 95% confidence interval: 0.98-1.0). The CT-CED group was older
(69.8 vs 64 years; P = .038), had higher initial NIHSS (14.6 vs 11; P = .01),
worse mRS (3.2 vs 2.4; P = .03), and longer LOS (8.4 vs 6.4; P = .05) compared
with those without CT-CED. A vascular occlusion in the territory of the infarct
was seen in 58% of patients with CT-CED versus 32% without CT-CED (P < .01).
Atrial fibrillation (AF) was diagnosed in 61% patients with CT-CED versus 22%
without (P < .01). CONCLUSION: The CT-CED is associated with higher initial
NIHSS, large vessel occlusion, and AF. Prospective studies are needed to
ascertain whether CT-CED may be utilized part of a screen for endovascular
therapy.
PMID- 28400901
TI - Comparing the Comprehensive Stroke Ward Versus Mixed Rehabilitation Ward-The
Importance of the Team in the Acute Stroke Care in a Case-Control Study.
AB - BACKGROUND AND PURPOSE: Ischemic stroke is one of the most frequent causes of
death in Brazil. Many measures have been taken to reduce this tragic outcome, and
one of those is the implementation of stroke units in hospitals. The aim of the
present study is to analyze the in-hospital complications for patients with
ischemic stroke admitted in a comprehensive stroke ward (CSW) as compared to
patients admitted in a mixed rehabilitation ward (MRW). METHODS: A retrospective
interventional study with historic controls of patients admitted to the Neurology
Division between January 2010 and October 2013. Patients admitted between January
2010 and September 2012 were included in the MRW group, and patients admitted
from October 2012 until October 2013 were included in the CSW group. Throughout
the whole study period, the same team assisted all the patients. Both groups were
paired in relation to age and gender. The rate of in-hospital complications,
mortality, and independency on discharge were evaluated in both groups. RESULTS:
Each group was comprised of 91 patients. There were no statistically significant
differences for any of the risk factors analyzed between the 2 groups nor for
outcome measures-in-hospital complications, mortality, and independence on
discharge. CONCLUSION: The present study demonstrated that in-hospital
complications, independence on discharge, and mortality have similar rates in
patients admitted to an MRW compared to patients admitted to a CSW, when the same
staff provided them with specialized in-hospital care. EVIDENCE LEVEL: Case
control study-Evidence Level 3.
PMID- 28400902
TI - A Novel Neuroscience Intermediate-Level Care Unit Model: Retrospective Analysis
of Impact on Patient Flow and Safety.
AB - BACKGROUND AND PURPOSE: Neurointensive care units have been shown to improve
patient outcomes across a variety of neurological and neurosurgical conditions.
However, the efficacy of less resource-intensive intermediate-level care units to
deliver similar care has not been well studied. The purpose of this study is to
evaluate the impact of neurocritical specialist comanagement on patient flow and
safety in a neuroscience intermediate-level care unit. METHODS: Our intervention
consisted of the addition of a physician with critical care experience as well as
training in neurology, anesthesiology, or intensive care to a neuroscience
intermediate-level care unit to comanage patients alongside neurology and
neurosurgery staff during weekday daytime hours. A retrospective analysis was
performed on prospectively collected data pertaining to all patients admitted to
the unit over a 3-year period, 1 year before our intervention and 2 years after.
Patient statistics including wait times to admission, length of stay (LOS), and
mortality were reviewed. RESULTS: Following the intervention, there were
significant reductions in wait times to unit admission from both the emergency
department and postanesthetic care unit, as well as reductions in the average
LOS. No significant safety concerns were identified. CONCLUSION: This study has
demonstrated that the optimization of a neuroscience intermediate-level care unit
involving comanagement of patients by a neurocritical specialist can reduce wait
times to admission and lengths of stay, with preserved safety outcomes.
PMID- 28400903
TI - Neurosarcoidosis Presenting With Recurrent Strokes: A Case Report and Literature
Review.
AB - Neurosarcoidosis is a rare but important cause of stroke as it is treatable.
Cases reported thus far have primarily been in young people who are relatively
healthy. Here we report the case of a 73-year-old woman presenting with recurrent
strokes and high-grade intracranial stenosis caused by probable neurosarcoidosis.
This is unique as neurosarcoidosis is not usually considered as an etiology for
recurrent strokes in our patient's age-group. We review and categorize published
cases of neurosarcoidosis causing stroke and describe a classification scheme for
certainty of diagnosis. Given the implications of this diagnosis for secondary
stroke prevention, we recommend that neurosarcoidosis be considered in the
differential for patients with few vascular risk factors, recurrent strokes
refractory to medical treatment, or possible vasculitis even in the elderly
patients.
PMID- 28400904
TI - Extensive Mobile Thrombus of the Internal Carotid Discovered After Intravenous
Thrombolysis: What Do I Do Now?
AB - This case report describes a rare presentation of ischemic stroke secondary to an
extensive internal carotid artery thrombus, subsequent therapeutic dilemma, and
clinical management. A 58-year-old man was administered intravenous (IV)
thrombolysis for right middle cerebral artery territory ischemic stroke symptoms.
A computed tomography angiogram of the head and neck following thrombolysis
showed a longitudinally extensive internal carotid artery thrombus originating at
the region of high-grade calcific stenosis. Mechanical embolectomy was deferred
because of risk of clot dislodgement and mild neurological symptoms. Recumbency
and hemodynamic augmentation were used acutely to support cerebral perfusion.
Anticoagulation was started 24 hours after thrombolysis. Carotid endarterectomy
was completed successfully within 1 week of presentation. Clinical outcome was
satisfactory with discharge modified Rankin Scale score 0. A longitudinally
extensive carotid artery thrombus poses a risk of dislodgement and hemispheric
stroke. Optimal management in these cases is not known with certainty. In our
case, IV thrombolysis, hemodynamic augmentation, delayed anticoagulation, and
carotid endarterectomy resulted in a favorable clinical outcome.
PMID- 28400905
TI - Computed Tomography Diagnosis of Terson Syndrome.
PMID- 28400906
TI - Gerstmann Syndrome in a Patient With Aggressive Mucormycosis.
PMID- 28400907
TI - Recurrent Focal Neurological Symptoms and Cortical Siderosis.
PMID- 28400908
TI - Facial Myokymias In Parry-Romberg Syndrome.
PMID- 28400909
TI - Traumatic Subarachnoid Hemorrhage With Immune Thrombocytopenia.
PMID- 28400910
TI - A Novel Cause of Inferior Olivary Hypertrophy.
PMID- 28400911
TI - Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant
Women with Gestational Diabetes Mellitus.
AB - Dysregulation of NO production is implicated in pregnancy-related diseases,
including gestational diabetes mellitus (GDM). The role of NO and its placental
targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO
derived posttranslational protein modification that can modulate biological
functions by forming NO-derived complexes with longer half-life, termed S
nitrosothiol (SNO). Our aim was to examine the presence of endogenous S
nitrosylated proteins in cysteine residues in relation to antioxidant defense,
apoptosis, and cellular signal transduction in placental tissue from control (n =
8) and GDM (n = 8) pregnancies. S-Nitrosylation was measured using the biotin
switch assay, while the expression and protein activity were assessed by
immunoblotting and colorimetric methods, respectively. Results indicated that
catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas,
and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2
and AKT was increased in GDM placentas, and their activities were inhibited.
Activities of caspase-3 and caspase-9 were increased, with the latter also
showing diminished nitrosylation levels. These findings suggest that S
nitrosylation is a little-known, but critical, mechanism by which NO directly
modulates key placental proteins in women with GDM and, as a consequence,
maternal and fetal anomalies during pregnancy can occur.
PMID- 28400913
TI - Corrigendum to "The Overexpression of NALP3 Inflammasome in Knee Osteoarthritis
Is Associated with Synovial Membrane Prolidase and NADPH Oxidase 2".
AB - [This corrects the article DOI: 10.1155/2016/1472567.].
PMID- 28400912
TI - Impact on Autophagy and Ultraviolet B Induced Responses of Treatment with the
MTOR Inhibitors Rapamycin, Everolimus, Torin 1, and pp242 in Human Keratinocytes.
AB - The mechanistic target of Rapamycin (MTOR) protein is a crucial signaling
regulator in mammalian cells that is extensively involved in cellular biology.
The function of MTOR signaling in keratinocytes remains unclear. In this study,
we detected the MTOR signaling and autophagy response in the human keratinocyte
cell line HaCaT and human epidermal keratinocytes treated with MTOR inhibitors.
Moreover, we detected the impact of MTOR inhibitors on keratinocytes exposed to
the common carcinogenic stressors ultraviolet B (UVB) and UVA radiation. As a
result, keratinocytes were sensitive to the MTOR inhibitors Rapamycin,
everolimus, Torin 1, and pp242, but the regulation of MTOR downstream signaling
was distinct. Next, autophagy induction only was observed in HaCaT cells treated
with Rapamycin. Furthermore, we found that MTOR signaling was insensitive to UVB
but sensitive to UVA radiation. UVB treatment also had no impact on the
inhibition of MTOR signaling by MTOR inhibitors. Finally, MTOR inhibition by
Rapamycin, everolimus, or pp242 did not affect the series of biological events in
keratinocytes exposed to UVB, including the downregulation of BiP and PERK,
activation of Histone H2A and JNK, and cleavage of caspase-3 and PARP. Our study
demonstrated that MTOR inhibition in keratinocytes cannot always induce
autophagy, and the MTOR pathway does not play a central role in the UVB triggered
cellular response.
PMID- 28400914
TI - Physical Exercise on Inflammatory Markers in Type 2 Diabetes Patients: A
Systematic Review of Randomized Controlled Trials.
AB - Background. Type 2 diabetes mellitus (T2DM) is a serious disease associated with
high morbidity and mortality. Scientific findings showed that physical exercise
is an option for treatment of these patients. This study's objective is to
investigate the effects of supervised aerobic and/or resistance physical training
on inflammatory markers in subjects with T2DM. Methods. A systematic review was
conducted on four databases, MEDLINE, CENTRAL, LILACS, and Scopus, and manual
search from 21 to 30 November 2016. Randomized clinical trials involving
individuals diagnosed with T2DM, who have undergone supervised training
protocols, were selected in this study. Results. Eleven studies were included.
Studies that evaluated control group versus aerobic exercise reported
controversial results about the effectiveness of physical training in modifying C
reactive protein (CRP) and cytokine levels. The only variable analyzed by the six
studies in comparison to the control group versus resistance exercise was CRP.
This protein showed no significant difference between groups. Between the two
modes of exercise (aerobic and resistance), only one study demonstrated that
aerobic exercise was more effective in reducing CRP. Conclusion. The evidence was
insufficient to prove that aerobic or resistance exercise improves systemic
levels of inflammatory markers in patients with T2DM.
PMID- 28400915
TI - Molecular Hydrogen Effectively Heals Alkali-Injured Cornea via Suppression of
Oxidative Stress.
AB - The aim of this study was to examine the effect of molecular hydrogen (H2) on the
healing of alkali-injured cornea. The effects of the solution of H2 in phosphate
buffered saline (PBS) or PBS alone topically applied on the alkali-injured rabbit
cornea with 0.25 M NaOH were investigated using immunohistochemical and
biochemical methods. Central corneal thickness taken as an index of corneal
hydration was measured with an ultrasonic pachymeter. Results show that
irrigation of the damaged eyes with H2 solution immediately after the injury and
then within next five days renewed corneal transparency lost after the injury and
reduced corneal hydration increased after the injury to physiological levels
within ten days after the injury. In contrast, in injured corneas treated with
PBS, the transparency of damaged corneas remained lost and corneal hydration
elevated. Later results-on day 20 after the injury-showed that in alkali-injured
corneas treated with H2 solution the expression of proinflammatory cytokines,
peroxynitrite, detected by nitrotyrosine residues (NT), and malondialdehyde (MDA)
expressions were very low or absent compared to PBS treated injured corneas,
where NT and MDA expressions were present. In conclusion, H2 solution favorably
influenced corneal healing after alkali injury via suppression of oxidative
stress.
PMID- 28400916
TI - Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1
dependent aldosterone production: Implications for heart failure therapy.
AB - Aldosterone mediates many of the physiological and pathophysiological/cardio
toxic effects of angiotensin II (AngII). Its synthesis and secretion from the
zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure
(HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein
coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal
through beta-arrestin-1 (betaarr1) or -2 (betaarr2), both of which mediate G
protein-independent signaling. Over the past decade, a second, Gq/11 protein
independent but betaarr1-dependent signaling pathway emanating from the
adrenocortical AT1R and leading to aldosterone production has become appreciated.
Thus, it became apparent that AT1R antagonists that block both pathways equally
well are warranted for fully effective aldosterone suppression in HF. This
spurred the comparison of all of the currently marketed angiotensin receptor
blockers (ARBs, AT1R antagonists or sartans) at blocking activation of the two
signaling modes (G protein-, and betaarr1-dependent) at the AngII-activated AT1R
and hence, at suppression of aldosterone in vitro and in vivo. Although all
agents are very potent inhibitors of G protein activation at the AT1R,
candesartan and valsartan were uncovered to be the most potent ARBs at blocking
betaarr activation by AngII and at suppressing aldosterone in vitro and in vivo
in post-myocardial infarction HF animals. In contrast, irbesartan and losartan
are virtually G protein-"biased" blockers at the human AT1R, with very low
efficacy for betaarr inhibition and aldosterone suppression. Therefore,
candesartan and valsartan (and other, structurally similar compounds) may be the
most preferred ARB agents for HF pharmacotherapy, as well as for treatment of
other conditions characterized by elevated aldosterone.
PMID- 28400917
TI - Coronary stenting: A matter of revascularization.
AB - In the last few decades, the recommended treatment for coronary artery disease
has been dramatically improved by percutaneous coronary intervention (PCI) and
the use of balloon catheters, bare metal stents (BMSs), and drug-eluting stents
(DESs). Catheter balloons were burdened by acute vessel occlusion or target
lesion re-stenosis. BMSs greatly reduced those problems holding up the vessel
structure, but showed high rates of in-stent re-stenosis, which is characterized
by neo-intimal hyperplasia and vessel remodeling leading to a re-narrowing of the
vessel diameter. This challenge was overtaken by first-generation DESs, which
reduced re-stenosis rates to nearly 5%, but demonstrated delayed arterial healing
and risk for late in-stent thrombosis, with inflammatory cells playing a pivotal
role. Finally, new-generation DESs, characterized by innovations in design, metal
composition, surface polymers, and anti-proliferative drugs, finally reduced the
risk for stent thrombosis and greatly improved revascularization outcomes. New
advances include bioresorbable stents potentially changing the future of
revascularization techniques as the concept bases upon the degradation of the
stent scaffold to inert particles after its function expired, thus theoretically
eliminating risks linked with both stent thrombosis and re-stenosis. Talking
about DESs also dictates to consider dual antiplatelet therapy (DAPT), which is a
fundamental moment in view of the good outcome duration, but also deals with
bleeding complications. The better management of patients undergoing PCI should
include the use of DESs and a DAPT finely tailored in consideration of the
potentially developing bleeding risk in accordance with the indications from last
updated guidelines.
PMID- 28400919
TI - Paroxysmal atrial fibrillation ablation: Achieving permanent pulmonary vein
isolation by point-by-point radiofrequency lesions.
AB - Pulmonary vein isolation by point-by-point radiofrequency catheter ablation
constitutes the cornerstone of catheter ablation strategies for the treatment of
atrial fibrillation. However, despite advances in pulmonary vein isolation
ablation strategies, long-term success rates after ablation remain suboptimal,
which highlights the need to develop techniques to achieve more durable lesions.
Strategies proposed to improve the durability of pulmonary vein isolation can be
divided into two groups: Those addressed to improving the quality of the lesion
and those that optimize the detection of acute PV reconnection during the
ablation procedure. This manuscript reviews the role and potential benefits of
these techniques according to current clinical evidence.
PMID- 28400918
TI - Patient selection for transcatheter aortic valve replacement: A combined clinical
and multimodality imaging approach.
AB - Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy
for patients affected by severe symptomatic aortic stenosis who are not eligible
for surgical intervention because of major contraindication or high operative
risk. Patient selection for TAVR should be based not only on accurate assessment
of aortic stenosis morphology, but also on several clinical and functional data.
Multi-Imaging modalities should be preferred for assessing the anatomy and the
dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the
first line tool in evaluation of this patients giving detailed anatomic
description of aortic valve complex and allowing estimating with enough
reliability the hemodynamic entity of valvular stenosis. Angiography should be
used to assess coronary involvement and plan a revascularization strategy before
the implant. Multislice computed tomography play a central role as it can give
anatomical details in order to choice the best fitting prosthesis, evaluate the
morphology of the access path and detect other relevant comorbidities.
Cardiovascular magnetic resonance and positron emission tomography are emergent
modality helpful in aortic stenosis evaluation. The aim of this review is to give
an overview on TAVR clinical and technical aspects essential for adequate
selection.
PMID- 28400920
TI - Accuracy of gestalt perception of acute chest pain in predicting coronary artery
disease.
AB - AIM: To test accuracy and reproducibility of gestalt to predict obstructive
coronary artery disease (CAD) in patients with acute chest pain. METHODS: We
studied individuals who were consecutively admitted to our Chest Pain Unit. At
admission, investigators performed a standardized interview and recorded 14 chest
pain features. Based on these features, a cardiologist who was blind to other
clinical characteristics made unstructured judgment of CAD probability, both
numerically and categorically. As the reference standard for testing the accuracy
of gestalt, angiography was required to rule-in CAD, while either angiography or
non-invasive test could be used to rule-out. In order to assess reproducibility,
a second cardiologist did the same procedure. RESULTS: In a sample of 330
patients, the prevalence of obstructive CAD was 48%. Gestalt's numerical
probability was associated with CAD, but the area under the curve of 0.61 (95%CI:
0.55-0.67) indicated low level of accuracy. Accordingly, categorical definition
of typical chest pain had a sensitivity of 48% (95%CI: 40%-55%) and specificity
of 66% (95%CI: 59%-73%), yielding a negligible positive likelihood ratio of 1.4
(95%CI: 0.65-2.0) and negative likelihood ratio of 0.79 (95%CI: 0.62-1.02).
Agreement between the two cardiologists was poor in the numerical classification
(95% limits of agreement = -71% to 51%) and categorical definition of typical
pain (Kappa = 0.29; 95%CI: 0.21-0.37). CONCLUSION: Clinical judgment based on a
combination of chest pain features is neither accurate nor reproducible in
predicting obstructive CAD in the acute setting.
PMID- 28400921
TI - Validity of electrocardiographic criteria for increased left ventricular mass in
young patients in the general population.
AB - AIM: To investigate validity of electrocardiographic (ECG) criteria for left
ventricular hypertrophy (LVH) in young adults. METHODS: Retrospectively,
echocardiograms showing LVH and concomitant electrocardiograms were collected in
patients 18 to 39 years old. A control group of patients without LVH was
collected. Using echocardiogram as the gold standard, electrocardiograms were
analyzed using common voltage criteria. RESULTS: Study included 100 subjects (52%
male, mean age = 28 +/- 6.8 years, 96% Hispanic or African-American) with 50% LVH
prevalence. Sensitivity and specificity for Sokolow-Lyon criteria were 24%
(95%CI: 13.5%-38.4%) and 88% (95%CI: 74.9%-95%). For Cornell criteria,
sensitivity was 32% (95%CI: 19.9%-46.8%) and specificity 98% (95%CI: 87.9%
99.8%). For R in aVL criteria, sensitivity was 12% (95%CI: 4.9%-25%) and
specificity 100% (95%CI: 91.1%-100%). CONCLUSION: In young adults common ECG
voltage criteria have low sensitivities and high specificities similar to other
age groups. Low sensitivities preclude these ECG criteria from serving as
effective screening tests.
PMID- 28400922
TI - Pheochromocytoma and stress cardiomyopathy: Insight into pathogenesis.
AB - AIM: To investigate the occurrence of cardiomyopathy (CMP) in a cohort of
patients with histologically proven pheochromocytoma (pheo), and to determine if
catecholamine excess was causative of the left ventricular (LV) dysfunction.
METHODS: A retrospective chart review spanning years 1998 through 2014 was
undertaken and patients with a diagnosis of pheo confirmed with histopathologic
examination were included. Presenting electrocardiograms and cardiac imaging
studies were reviewed. Transthoracic echocardiography (TTE), ventriculography or
single positron emission computed tomography imaging was evaluated and if
significant abnormalities [left ventricular hypertrophy (LVH) or LV dysfunction]
were noted in the pre operative period a follow up post-operative study was also
analyzed. Multivariate analysis using logistic regression was used to investigate
independent predictors for outcomes of interest, LV dysfunction and LVH. RESULTS:
We identified 18 patients with diagnosis of pheo confirmed on pathology. Mean age
was 54.3 +/- 19.3 years and 11 (61.1%) patients were females. 50% of such
patients had either resistant hypertension or labile blood pressures during
hospitalization, which had raised suspicion for a pheo. Cardiac imaging studies
were available for 12 (66.7%) patients at the time of inclusion into study and
preceding the adrenalectomy. 7 (58.3%) patients with a TTE available for review
had mild or more severe LVH while 3 (25%) patients had LV dysfunction of
presumably acute onset. In a multivariate analysis, elevated catecholamine levels
as assessed by urinary excretion of metabolites was not an independent predictor
of development of LV systolic dysfunction or of presence of LVH on TTE. Two
female patients with a preceding history of hypertension had marked LV
hypertrophy and systolic anterior motion of the mitral valve. Prolongation of the
QTc interval was noted in 5 (27.8%) patients but no acute arrhythmias were
observed in any patient. CONCLUSION: This study adds to the growing body of
literature on the predilection of patients with pheochromocytomas to develop non
ischemic CMP. Degree of catecholamine excess as measured by urinary secretion of
metabolites did not predict the development of CMP but 2 of 3 patients developed
CMP in the setting of significant acute physiologic stress. Our findings provide
support to the proposed etiologic role of elevated catecholamines in TC and other
stress induced forms of CMP, however, activation of a brain-neural-cardiac axis
from acute stress and local release of catecholamines but not chronic
catecholamine elevations are likely to be responsible in pheo related CMP.
PMID- 28400923
TI - Significance of inferior wall ischemia in non-dominant right coronary artery
anatomy.
AB - AIM: To investigate the relationship of inferior wall ischemia on myocardial
perfusion imaging in patients with non-dominant right coronary artery anatomy.
METHODS: This was a retrospective observational analysis of consecutive patients
who presented to the emergency department with primary complaint of chest pain.
Only patients who underwent single photon emission computed tomography (SPECT)
myocardial perfusion imaging (MPI) were included. Patients who showed a
reversible defect on SPECT MPI and had coronary angiography during the same
hospitalization was analyzed. Patients with prior history of coronary artery
disease (CAD) including history of percutaneous coronary intervention and
coronary artery bypass graft surgerys were excluded. True positive and false
positive results were identified on the basis of hemodynamically significant CAD
on coronary angiography, in the same territory as identified on SPECT MPI.
Coronary artery dominance was determined on coronary angiography. Patients were
divided into group 1 and group 2. Group 1 included patients with non-dominant
right coronary artery (RCA) (left dominant and codominant). Group 2 included
patients with dominant RCA anatomy. Demographics, baseline characteristics and
positive predictive value (PPV) were analyzed for the two groups. RESULTS: The
mean age of the study cohort was 57.6 years. Sixty-one point seven percent of the
patients were males. The prevalence of self-reported diabetes mellitus,
hypertension and dyslipidemia was 36%, 71.9% and 53.9% respectively. A comparison
of baseline characteristics between the two groups showed that patients with a
non-dominant RCA were more likely to be men. For inferior wall ischemia on SPECT
MPI, patients in study group 2 had a significantly higher PPV, 32/42 (76.1%),
compared to patients in group 1, in which only 3 out of the 29 patients (10.3%)
had true positive results (P value < 0.001 Z test). The difference remained
statistically significant even when only patients with left dominant coronary
system (without co-dominant) were compared to patients with right dominant system
(32/40, 76.1% in right dominant group, 3/19, 15.8% in left dominant group, P
value < 0.001 Z test). There was no significant difference in mean hospital stay,
re-hospitalization, and in-hospital mortality between the two groups. CONCLUSION:
The positive predictive value of SPECT MPI for inferior wall ischemia is affected
by coronary artery dominance. More studies are needed to explain this phenomenon.
PMID- 28400925
TI - Children with transposition of the great arteries: Should they actually be born
in Nigeria?
AB - AIM: To describe the clinical and echocardiographic features of Nigerian children
with transposition of the great arteries and emphasize the need for collaboration
with cardiac centres in the developed countries to be able to salvage the
children. METHODS: Prospective and cross sectional involving consecutive patients
diagnosed with transposition of the great arteries using clinical evaluation and
echocardiography at the Paediatric Department of Lagos State University Teaching
Hospital, Lagos Nigeria as part of a large study between January 2007 and
December 2015. RESULTS: There were 51 cases of transposition of the great
arteries within the study period with a male to female ratio of 2:1 and a
prevalence of 1.55 per 10000 among population of children who presented to centre
during the study. Its proportion amongst children with congenital heart disease
was 4.9%, while it was 15.4% among those with cyanotic congenital heart disease.
The mean age +/- SD of the subjects was 10.3 +/- 21.8 mo. Up to 70% of the
patients were less than 6 mo of age at initial presentation. The most common mode
of presentation was cyanosis. The most common associated intracardiac anomaly was
ventricular septal defect which occurred in 56% of the patients. CONCLUSION:
Transposition of the great arteries is as common in Nigeria as in the other parts
of the world. The most common mode of presentation was cyanosis. There is an
urgent need to establish paediatric cardiac centres in Nigeria if these children
are to be salvaged.
PMID- 28400924
TI - Risk of ventricular arrhythmia in patients with myocardial infarction and non
obstructive coronary arteries and normal ejection fraction.
AB - AIM: To assess the arrhythmic determinants and prognosis of patients presenting
with myocardial infarction and non-obstructive coronary arteries (MINOCA) with
normal ejection fraction (EF). METHODS: This is an observational analysis of 131
MINOCA patients with normal EF. Three cardiac magnetic resonance (CMR) diagnosis
classes were recognized according to the late gadolinium enhancement (LGE)
pattern: Myocardial infarction (MI) (n = 34), myocarditis (n = 47), and "no LGE"
(n = 50). Ventricular events occurring during hospitalization were recorded and
the entire population was followed-up at 1 year. RESULTS: Ventricular arrhythmia
was observed in 18 (13.8%) patients during hospitalization. The "no LGE" patients
experienced fewer ventricular events than the MI and myocarditis patients [4.0%
vs 26.5% and 14.9%, respectively (P = 0.013)]. There was no significant
difference between the MI and myocarditis groups. On multivariate analysis, LGE
transmural extent [OR = 1.52 (1.08-2.15), P = 0.017] and ST-segment elevation [OR
= 4.65 (1.61-13.40), P = 0.004] were independent predictors of ventricular
arrhythmic events, irrespective of the diagnosis class. Finally, no patient
experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year.
CONCLUSION: MINOCA patients with normal EF presented no 1-year cardiovascular
events, irrespective of the CMR diagnosis class. LGE transmural extent and ST
segment elevation at admission are risk markers of ventricular arrhythmia during
hospitalization.
PMID- 28400926
TI - Early stent thrombosis secondary to food allergic reaction: Kounis syndrome
following rice pudding ingestion.
AB - Kounis syndrome is the concurrence of coronary spasm, acute myocardial infarction
or stent thrombosis, with allergic reactions in the setting of mast-cell and
platelet activation. In this report Kounis syndrome manifesting as stent
thrombosis with left ventricular thrombus formation was triggered by a food
induced allergic reaction. The allergic reaction to food was confirmed by oral
rice pudding ingredients challenge test while skin tests were inconclusive. To
our knowledge, this is first report of early stent thrombosis secondary to food
allergic reaction in a 70-year-old man patient who was found to have left
ventricular thrombus and undiagnosed hypertrophic cardiomyopathy.
PMID- 28400927
TI - Importance of a second spasm provocation test: Four cases with an initial
negative spasm provocation test.
AB - The spasm provocation test (SPT) is an important test in the diagnosis of
vasospastic angina (VSA). In many cases, this test is performed as the gold
standard test, and VSA is considered not present if the SPT is negative. However,
some patients continue to experience chest symptoms despite a negative SPT. In
this study, we report four cases in which SPT was repeated to evaluate chest
symptoms despite the negative results of the first SPT. Two men in their 70s, one
woman in her 60s, and one woman in her 70s, all with chest symptoms, underwent a
second SPT at 4, 3, 2, and 3 years, respectively, after the first SPT, which was
negative. Three patients had positive results in the second SPT (75%). In
conclusion, even when SPT is negative, the diagnosis of VSA should be made with
clinical symptoms in consideration. In some cases, a second SPT may be required
to confirm the diagnosis of VSA.
PMID- 28400928
TI - Progeria of the Heart in Type 1 Diabetic Children?
PMID- 28400929
TI - Role of Echocardiography in Diagnosing Myocardial Ischemia at Emergency
Department.
PMID- 28400930
TI - The Relationships between Body Mass Index and Left Ventricular Diastolic Function
in a Structurally Normal Heart with Normal Ejection Fraction.
AB - BACKGROUND: We conducted research to determine the effect of the weight on left
ventricular (LV) diastolic function in Asians, who are at greater risk of
cardiovascular events compared to individuals from Western countries with similar
body mass indices (BMIs). METHODS: We studied 543 participants with structurally
normal hearts and normal ejection fractions. Participants were classified as
normal-weight (BMI < 23.0 kg/m2), overweight (BMI 23.0-27.4 kg/m2), or obese (BMI
>= 27.5 kg/m2). Peak E velocity, peak A velocity, and E' velocity were measured
and E/E' was calculated. RESULTS: Overweight participants had lower E than normal
weight participants (p = 0.001). E' velocities in overweight and obese
participants were less than those in normal weight participants (both p < 0.001).
The E/E' ratio in obese participants was higher compared to the value in normal
weight participants (p < 0.001) and overweight participants (p = 0.025). BMI was
associated with E (R = -0.108), A (R = 0.123), E' (R = -0.229), and E/E' ratio (R
= 0.138) (all p < 0.05). In multivariate analyses, BMI was independently
associated with higher A, lower E', and higher E/E'. The risk of diastolic
dysfunction was significantly higher among overweight [adjusted odds ratio:
2.088; 95% confidence interval (CI): 1.348-3.235; p = 0.001] and obese
participants (adjusted odds ratio: 5.910; 95% CI: 2.871-12.162; p < 0.001)
compared to normal-weight participants. CONCLUSION: Obesity and overweight
independently predicted diastolic dysfunction. An optimal body weight lower than
the universal cut-off is reasonable for preventing LV heart failure in Asians.
PMID- 28400931
TI - Evaluation of Cardiac Functions in Children and Adolescents with Type 1 Diabetes.
AB - BACKGROUND: Cardiac dysfunction in patients with type 1 diabetes (T1D) represents
one of the serious complications. To evaluate the cardiac function in children
with T1D by conventional echocardiography and tissue Doppler imaging (TDI).
METHODS: The study included 40 T1D patients (age between 6 and 16 years) with > 5
years duration of diabetes and 42 healthy control children. The patients were
subjected to clinical evaluation and laboratory investigations [glycosylated
hemoglobin A1c (HbA1c), serum lipids and lipoproteins]. Conventional
echocardiography and TDI were performed to patients and controls. RESULTS: The
patients had lower early diastolic filling velocity (E wave) of the tricuspid
valve and mitral valves with a p value of (0.000 and 0.006, respectively). TDI
revealed that patients had lower S'velocity of the T1D, shorter isovolumic
contraction time, longer isovolumic relaxation time and lower E/E' of the right
ventricle than controls (p value 0.002, 0.001, 0.004, 0.003, and 0.016,
respectively). The left ventricle (LV)-T1D of the patients was significantly
higher (p value 0.02). Twenty eight patients had poor glycemic control without
significant differences between them and those with good glycemic control
regarding echocardiographic data. Patients with dyslipidemia (13 patients) had
higher late diastolic filling velocity of the mitral valve (A) and the lower LV
late tissue velocity (A') (p wave 0.047 and 0.015). No correlation existed
between the duration of illness or the level of HbA1c and the echocardiographic
parameters. CONCLUSION: Diabetic children have evidence of echocardiographic
diastolic dysfunctions. Periodic cardiac evaluation with both conventional and
tissue Doppler echocardiography is recommended for early detection of this
dysfunction.
PMID- 28400932
TI - Role of Quantitative Wall Motion Analysis in Patients with Acute Chest Pain at
Emergency Department.
AB - BACKGROUND: Evaluation of acute chest pain in emergency department (ED), using
limited resource and time, is still very difficult despite recent development of
many diagnostic tools. In this study, we tried to determine the applicability of
new semi-automated cardiac function analysis tool, velocity vector imaging (VVI),
in the evaluation of the patients with acute chest pain in ED. METHODS: We
prospectively enrolled 48 patients, who visited ED with acute chest pain, and
store images to analyze VVI from July 2005 to July 2007. RESULTS: In 677 of 768
segments (88%), the analysis by VVI was feasible among 48 patients. Peak systolic
radial velocity (Vpeak) and strain significantly decreased according to visual
regional wall motion abnormality (Vpeak, 3.50 +/- 1.34 cm/s for normal vs. 3.46
+/- 1.52 cm/s for hypokinesia, 2.51 +/- 1.26 for akinesia, p < 0.01; peak
systolic radial strain -31.74 +/- 9.15% fornormal, -24.33 +/- 6.28% for
hypokinesia, -20.30 +/- 7.78% for akinesia, p < 0.01). However, the velocity
vectors at the time of mitral valve opening (MVO) were directed outward in the
visually normal myocardium, inward velocity vectors were revealed in the visually
akinetic area (VMVO, -0.85 +/- 1.65 cm/s for normal vs. 0.10 +/- 1.46 cm/s for
akinesia, p < 0.001). At coronary angiography, VMVO clearly increased in the
ischemic area (VMVO, -0.88+1.56 cm/s for normal vs. 0.70 + 2.04 cm/s for ischemic
area, p < 0.01). CONCLUSION: Regional wall motion assessment using VVI showed
could be used to detect significant ischemia in the patient with acute chest pain
at ED.
PMID- 28400933
TI - Impact of Contrast Echocardiography on Assessment of Ventricular Function and
Clinical Diagnosis in Routine Clinical Echocardiography: Korean Multicenter
Study.
AB - BACKGROUND: Fundamental echocardiography has some drawbacks in patients with
difficult-to-image echocardiograms. The aim of this study is to evaluate impact
of contrast echocardiography (CE) on ventricular function assessment and clinical
diagnosis in routine clinical echocardiography. METHODS: Two hundred sixty
patients were prospectively enrolled over 3 years in 12 medical centers in Korea.
General image quality, the number of distinguishable segments, ability to assess
regional wall motion, left ventricular (LV) apex and right ventricle (RV)
visualization, LV ejection fraction, changes in diagnostic or treatment plan were
documented after echocardiography with and without ultrasound contrast agent.
RESULTS: Poor or uninterpretable general image was 31% before contrast use, and
decreased to 2% (p<0.05) after contrast use. The average number of visualized LV
segments was 9.53 before contrast use, and increased to 14.46 (p<0.001) after
contrast use. The percentage of poor or not seen LV regional wall motion was
decreased from 28.4% to 3.5% (p<0.001). The percentage of poor or not seen LV
apex and RV was decreased from 49.4% to 2.4% (p<0.001), from 30.5% to 10.5%
(p<0.001), respectively. Changes in diagnostic procedure and treatment plan after
CE were 30% and 29.6%, respectively. CONCLUSION: Compared to fundamental
echocardiography, CE impacted LV function assessment and clinical decision making
in Korean patients who undergo routine echocardiography.
PMID- 28400934
TI - Quadricuspid Aortic Valve Complicated with Severe Aortic Regurgitation and Left
Sided Inferior Vena Cava.
PMID- 28400935
TI - Statin Induced Regression of Cardiomyopathy Trial: A Randomized, Placebo
controlled Double-blind Trial.
AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM), characterized by a thickened,
fibrotic myocardium, remains the most common cause of sudden cardiac death in
young adults. Based on animal and clinical data, we hypothesized that
atorvastatin would induce left ventricular (LV) mass regression. METHODS: Statin
Induced Regression of Cardiomyopathy Trial (SIRCAT) was a randomized, placebo
controlled study. The primary endpoint was change in LV mass measured by cardiac
magnetic resonance imaging 12 months after treatment with once-daily atorvastatin
80 mg or placebo. A key secondary endpoint was diastolic dysfunction measured
echocardiographically by transmitral flow velocities. SIRCAT is registered with
www.clinicaltrials.gov (NCT00317967). RESULTS: Of 222 screened patients, 22 were
randomized evenly to atorvastatin and placebo. The mean age was 47 +/- 10 years,
and 15 (68%) were male. All subjects completed the protocol. At baseline, LV
masses were 197 +/- 76 g and 205 +/- 82 g in the placebo and atorvastatin groups,
respectively. After 12 months treatment, the LV masses in the placebo and
atorvastatin groups were 196 +/- 80 versus 206 +/- 92 g (P = 0.80), respectively.
Echocardiographic indices were not different in the two groups at baseline. After
12 months, diastolic dysfunction as assessed using transmitral flow velocities
E/E', A/A', and peak systolic mitral velocity showed no benefit from
atorvastatin. CONCLUSIONS: In patients with HCM, atorvastatin did not cause LV
mass regression or improvements in LV diastolic function.
PMID- 28400936
TI - Clinical Profile and Management of Poisoning with Suicide Tree: An Observational
Study.
AB - INTRODUCTION: The clinical features, management, and the associations of dosage
in poisoning with the cardiotoxic plant Cerbera odollam (suicide tree),
responsible for more than half of plant poisoning deaths in the South Indian
State of Kerala alone, have not been evaluated. There are only few studies on its
clinical features and none on the usage of cardiac pacing in its management,
given its rarity in the Western world. We depend on data for similar toxins to
form our management protocols. AIMS: Our aim was to describe the clinical
features of C. odollam poisoning, dosage, and its relations to clinical features
and pacemaker initiation therapy and to study the characteristics of temporary
pacemaker therapy in its management. SUBJECTS AND METHODS: This study was
conducted in fifty consecutive cases who presented with a history of C. odollam
poisoning from whom clinical data were obtained. Cases initiated on temporary
cardiac pacemaker therapy due to the toxin effects were also studied. Effect of
dosage on various clinical manifestations and pacing was analyzed. RESULTS: All
cases were due to suicidal ingestion. Vomiting (54%), thrombocytopenia (50%), and
sinus bradycardia (32%) were the most common features. The need for cardiac
pacing had a significant association with dosage in kernels ingested (P < 0.05)
and with thrombocytopenia (P < 0.05). There was no association between
hyperkalemia and death. Thirty-six percent of cases had to be paced, of which 16%
died. In-hospital mortality of odollam poisoning was 12%. CONCLUSIONS: C. odollam
poisoning cases merit monitoring and treatment in Intensive Care Unit with
facilities for electrocardiographic monitoring and temporary cardiac pacing. The
clinical features and the factors associated with mortality are different from
other cardiac glycosides.
PMID- 28400937
TI - Graft Compression by Drain Tube.
AB - Hemodynamic compromise immediately after chest closure can be potentially fatal
event. Such condition warrants urgent reopening of sternum. In the present case,
we discover An uncommon cause of unstable hemodynamics.
PMID- 28400938
TI - Uhl's Anomaly: A Rare Case of Portal Hypertension.
AB - Uhl's anomaly is a rare congenital heart disease characterized by partial or
complete absence of the right ventricular myocardium and high early mortality
rates. We describe a case of Uhl's anomaly in a 27-year-old young male patient
presenting with portal hypertension and esophageal varices. In this article, we
review the literature associated with this condition and highlight a rare
presentation of a rare disease. This report adds to our current knowledge of this
exceedingly rare disorder.
PMID- 28400939
TI - Intracardiac Penetrating Injury with Right Femoral Artery Embolism due to Blast
Injury.
AB - Embolization due to blast injury with projectiles entering the bloodstream from
the heart is a rare event that is unlikely to be suspected during the initial
assessment of trauma patients. We report a case in which a missile penetrating
the heart chambers managed to embolize and occlude the right common femoral
artery. This was successfully managed by means of a multidisciplinary approach
that included exploration, cardiorrhaphy, and embolectomy.
PMID- 28400940
TI - Early Diagnosis of Penetrating Cardiac and Pleural Injury by Extended Focused
Assessment with Sonography for Trauma.
AB - In India, stab injury is not uncommon, but identifying potential life threatening
conditions in the emergency room (ER) and initiating prompt treatment are
challenging. This is a case report of a young patient who presented to the ER
with assault injury to the chest and shock; timely extended focused assessment
with sonography for trauma helped to fast-track the patient to the operating
room. A brief review of diagnosis and management of penetrating cardiac injury is
presented herewith.
PMID- 28400941
TI - Abnormal Color Flow Signal Traversing the Myocardial Wall: Not Everything is What
it Appears to Be.
AB - A case of a patient presenting with an acute myocardial infarction is presented.
A transthoracic echocardiographic examination revealed an abnormal color flow
signal that traversed the myocardial wall from a large inferior aneurysm and
initially considered to be a ventricular septal defect. However, further
echocardiographic manipulation utilizing modified views along with sequential
injections of both agitated saline and Definity(r) proved very useful to identify
a pseudoaneurysm. There was no further need for any other diagnostic test, and
the patient was treated surgically, undergoing successful repair of the
pseudoaneurysm as well as coronary artery bypass grafting of the left coronary
artery.
PMID- 28400942
TI - Treatment of Distal Left Anterior Descending Artery Perforation with Fat
Embolization.
AB - Coronary perforation is a potentially fatal complication during percutaneous
coronary intervention. Reports have shown that it occurs in 0.2 to 0.6% of all
patients undergoing the procedures. Although the frequency of coronary
perforation is low, it is a serious and potentially life-threatening situation
that warrants prompt recognition and management. Here we present a case of distal
coronary perforation, and review the management of coronary perforation in the
current practice.
PMID- 28400944
TI - A Flower Offering.
PMID- 28400943
TI - Superior Vena Cava Syndrome-like Phenomenon on Vascular Access.
PMID- 28400945
TI - Evolution of Myocardial Infarction and its Biomarkers: A Historical Perspective.
PMID- 28400946
TI - The state of asthma epidemiology: an overview of systematic reviews and their
quality.
AB - BACKGROUND: Recently, we have published an overview of systematic reviews in
allergy epidemiology and identified asthma as the most commonly reviewed allergic
disease. Building on this work, we aimed to investigate the quality of systematic
reviews in asthma using the AMSTAR checklist and to provide a reference for
future, more in-depth assessment of the extent of previous knowledge. METHODS: We
included all 307 systematic reviews indexed with asthma, including occupational
asthma, and/or wheeze from our previous search in PubMed and EMBASE up to
December 2014 for systematic reviews on epidemiological research on allergic
diseases. Topics of the included systematic reviews were indexed and we applied
the AMSTAR checklist for methodological quality to all. Statistical analyses
include description of lower and upper bounds of AMSTAR scores and variation
across publication time and topics. RESULTS: Of 43 topics catalogued, family
history, birth weight, and feeding of formula were only covered once in
systematic reviews published from 2011 onwards. Overall, at least one meta
analysis was conducted for all topics except for "social determinants",
"perinatal", "birth weight", and "climate". AMSTAR quality scores were
significantly higher in more recently published systematic reviews, in those with
meta-analysis, and in Cochrane reviews. There was evidence of variation of
quality across topics even, after accounting for these characteristics. Genetic
factors in asthma development were often covered by systematic reviews with some
evidence of unsubstantiated updates or repetition. CONCLUSIONS: We present a
comprehensive overview with an indexed database of published systematic reviews
in asthma epidemiology including quality scores. We highlight some topics
including active smoking and pets, which should be considered for future
systematic reviews. We propose that our search strategy and database could be a
basis for topic-specific overviews of systematic reviews in asthma epidemiology.
PMID- 28400948
TI - Zika: information in the nick of time.
PMID- 28400947
TI - Mutations in IFT-A satellite core component genes IFT43 and IFT121 produce short
rib polydactyly syndrome with distinctive campomelia.
AB - BACKGROUND: Skeletal ciliopathies comprise a spectrum of ciliary malfunction
disorders that have a profound effect on the skeleton. Most common among these
disorders is short rib polydactyly syndrome (SRPS), a recessively inherited
perinatal lethal condition characterized by a long narrow chest, markedly
shortened long bones, polydactyly and, often, multi-organ system involvement.
SRPS shows extensive locus heterogeneity with mutations in genes encoding
proteins that participate in cilia formation and/or function. RESULTS: Herein we
describe mutations in IFT43, a satellite member of the retrograde IFT-A complex,
that produce a form of SRPS with unusual bending of the ribs and appendicular
bones. These newly described IFT43 mutations disrupted cilia formation, produced
abnormalities in cartilage growth plate architecture thus contributing to altered
endochondral ossification. We further show that the IFT43 SRPS phenotype is
similar to SRPS resulting from mutations in the gene encoding IFT121 (WDR35), a
direct interactor with IFT43. CONCLUSIONS: This study defines a new IFT43
associated phenotype, identifying an additional locus for SRPS. The data
demonstrate that IFT43 is essential for ciliogenesis and that the mutations
disrupted the orderly proliferation and differentiation of growth plate
chondrocytes, resulting in a severe effect on endochondral ossification and
mineralization. Phenotypic similarities with SRPS cases resulting from mutations
in the gene encoding the IFT43 direct interacting protein IFT121 suggests that
similar mechanisms may be disrupted by defects in these two IFT-A satellite
interactors.
PMID- 28400949
TI - Men's health: time for a new approach to policy and practice?
PMID- 28400950
TI - Economics in "Global Health 2035": a sensitivity analysis of the value of a life
year estimates.
AB - BACKGROUND: In "Global health 2035: a world converging within a generation," The
Lancet Commission on Investing in Health (CIH) adds the value of increased life
expectancy to the value of growth in gross domestic product (GDP) when assessing
national well-being. To value changes in life expectancy, the CIH relies on
several strong assumptions to bridge gaps in the empirical research. It finds
that the value of a life year (VLY) averages 2.3 times GDP per capita for low-
and middle-income countries (LMICs) assuming the changes in life expectancy they
experienced from 2000 to 2011 are permanent. METHODS: The CIH VLY estimate is
based on a specific shift in population life expectancy and includes a 50 percent
reduction for children ages 0 through 4. We investigate the sensitivity of this
estimate to the underlying assumptions, including the effects of income, age, and
life expectancy, and the sequencing of the calculations. FINDINGS: We find that
reasonable alternative assumptions regarding the effects of income, age, and life
expectancy may reduce the VLY estimates to 0.2 to 2.1 times GDP per capita for
LMICs. Removing the reduction for young children increases the VLY, while
reversing the sequencing of the calculations reduces the VLY. CONCLUSION: Because
the VLY is sensitive to the underlying assumptions, analysts interested in
applying this approach elsewhere must tailor the estimates to the impacts of the
intervention and the characteristics of the affected population. Analysts should
test the sensitivity of their conclusions to reasonable alternative assumptions.
More work is needed to investigate options for improving the approach.
PMID- 28400951
TI - Contribution of community health workers to improving access to timely and
appropriate case management of childhood fever in Mozambique.
AB - BACKGROUND: Large scale evaluations in several settings have demonstrated that
lay community health workers can be trained to provide quality case management of
childhood illnesses. In 2010, Mozambique introduced the integrated community case
management (iCCM) strategy to reach children in remote areas with care provided
through Agentes Polivalentes Elementares (APEs). We assessed the contribution of
the program to improved care-seeking and appropriate treatment of childhood
febrile illness in Nampula Province. METHODS: We used a post-test quasi
experimental design with three intervention and one comparison districts to
compare access and appropriateness of care for sick children in Nampula province.
We carried out a household survey in the study districts to measure levels of
care-seeking and treatment of childhood fever after approximately two years of
full implementation of the iCCM program in the intervention districts. We also
assessed consistency of care with standard case management protocols comparing
children receiving care from (APEs) to those receiving care from first-level
health facilities. RESULTS: A total of 773 children 6-59 months with fever in the
last two weeks were included in the study. In iCCM served areas, APEs were the
predominant source of care and treatment; 87.1% (95% confidence interval CI 80.8
93.4) of children 6-59 months with fever who sought care were taken first to an
APE and APEs accounted for 86.2% (95% CI 79.7-92.7) of all first-line
antimalarial treatments. Public health facilities were the leading source of care
in comparison areas, providing care to 86.1% (95% CI 79.0-93.3) of children with
fever taken for care outside the home. Timeliness of treatment was significantly
better in intervention areas, where 63.9% (95% CI 54.4-73.3) of children received
treatment within 24 hours of symptom onset compared to 37.5% (95% CI 31.1-43.9)
in comparison areas. Children taken first to an APE were more likely to receive a
rapid diagnostic test (RDT) (68.1%; 95% CI 57.2-79.0) and to have their
respiratory rate assessed (60.0%; 95% CI 45.4-74.6) compared to children taken to
health facilities (41.4%; 95% CI33.7-49.2 and 19.4%; 95% CI 8.4-30.5,
respectively). Overall, 61.3% (95% CI 51.5-71.0) of children with fever receiving
care from APEs received the correct drug within 24 hours and for the correct
duration compared to 26.0% (95% CI 18.2-33.9) of those receiving care from health
facilities. CONCLUSION: iCCM contributed to improved timely and appropriate
treatment for fever for children living far from facilities. Trained, supplied
and supervised APEs provided care consistent with iCCM protocols and performed
significantly better than first level facilities on most measures of adherence to
case management protocols. These findings reinforce the need for comprehensive
efforts to strengthen the health system in Mozambique to enable reliable support
for quality of case management of childhood illness at both health facility and
community levels.
PMID- 28400952
TI - Alcohol-attributed disease burden and alcohol policies in the BRICS-countries
during the years 1990-2013.
AB - BACKGROUND: We aimed to assess alcohol consumption and alcohol-attributed disease
burden by DALYs (disability adjusted life years) in the BRICS countries (Brazil,
Russia, India, China and South Africa) between 1990 and 2013, and explore to what
extent these countries have implemented evidence-based alcohol policies during
the same time period. METHODS: A comparative risk assessment approach and
literature review, within a setting of the BRICS countries. Participants were the
total populations (males and females combined) of each country. Levels of alcohol
consumption, age-standardized alcohol-attributable DALYs per 100 000 and alcohol
policy documents were measured. RESULTS: The alcohol-attributed disease burden
mirrors level of consumption in Brazil, Russia and India, to some extent in
China, but not in South Africa. Between the years 1990-2013 DALYs per 100 000
decreased in Brazil (from 2124 to 1902), China (from 1719 to 1250) and South
Africa (from 2926 to 2662). An increase was observed in Russia (from 4015 to
4719) and India (from 1574 to 1722). Policies were implemented in all of the
BRICS countries and the most common were tax increases, drink-driving measures
and restrictions on advertisement. CONCLUSIONS: There was an overall decrease in
alcohol-related DALYs in Brazil, China and South Africa, while an overall
increase was observed in Russia and India. Most notably is the change in DALYs in
Russia, where a distinct increase from 1990-2005 was followed by a steady
decrease from 2005-2013. Even if assessment of causality cannot be done, policy
changes were generally followed by changes in alcohol-attributed disease burden.
This highlights the importance of more detailed research on this topic.
PMID- 28400953
TI - Maternal mortality as a Millennium Development Goal of the United Nations: a
systematic assessment and analysis of available data in threshold countries using
Indonesia as example.
AB - BACKGROUND: In 2015 the proposed period ended for achieving the Millennium
Development Goals (MDG) of the United Nations targeting to lower maternal
mortality worldwide by ~ 75%. 99% of these cases appear in developing and
threshold countries; but reports mostly rely on incomplete or unrepresentative
data. Using Indonesia as example, currently available data sets for maternal
mortality were systematically reviewed. METHODS: Besides analysis of
international and national data resources, a systematic review was carried out
according to Cochrane methodology to identify all data and assessments regarding
maternal mortality. RESULTS: Overall, primary data on maternal mortality differed
significantly and were hardly comparable. For 1990 results varied between 253/100
000 and 446/100 000. In 2013 data appeared more conclusive (140-199/100 000). An
annual reduction rate (ARR) of -2.8% can be calculated. CONCLUSION: Reported data
quality of maternal mortality in Indonesia is very limited regarding
comprehensive availability and methodology. This limitation appears to be of
general importance for the targeted countries of the MDG. Primary data are rare,
not uniformly obtained and not evaluated by comparable methods resulting in very
limited comparability. Continuous small data set registration should have high
priority for analysis of maternal health activities.
PMID- 28400954
TI - Increasing use of mental health services in remote areas using mobile technology:
a pre-post evaluation of the SMART Mental Health project in rural India.
AB - BACKGROUND: About 25% of the Indian population experience common mental disorders
(CMD) but only 15-25% of them receive any mental health care. Stigma, lack of
adequate mental health professionals and mental health services account for this
treatment gap, which is worse in rural areas. Our project evaluated task shifting
and mobile-technology based electronic decision support systems to enhance the
ability of primary care health workers to provide evidence-based mental health
care for stress, depression, and suicidal risk in 30 remote villages in the state
of Andhra Pradesh, India. METHODS: The Systematic Medical Appraisal Referral and
Treatment (SMART) Mental Health project between May 2014 and April 2016 trained
lay village health workers (Accredited Social Health Activists - ASHAs) and
primary care doctors to screen, diagnose and manage individuals with common
mental disorders using an electronic decision support system. An anti-stigma
campaign using multi-media approaches was conducted across the villages at the
outset of the project. A pre-post evaluation using mixed methods assessed the
change in mental health service utilization by screen positive individuals. This
paper reports on the quantitative aspects of that evaluation. RESULTS: Training
was imparted to 21 ASHAs and 2 primary care doctors. 5007 of 5167 eligible
individuals were screened, and 238 were identified as being positive for common
mental disorders and referred to the primary care doctors for further management.
Out of them, 2 (0.8%) had previously utilized mental health services. During the
intervention period, 30 (12.6%) visited the primary care doctor for further
diagnosis and treatment, as advised. There was a significant reduction in the
depression and anxiety scores between start and end of the intervention among
those who had screened positive at the beginning. Stigma and mental health
awareness in the broader community improved during the project. CONCLUSIONS: The
intervention led to individuals being screened for common mental disorders by
village health workers and increase in mental health service use by those
referred to the primary care doctor. The model was deemed feasible and
acceptable. The effectiveness of the intervention needs to be demonstrated using
more robust randomized controlled trials, while addressing the issues identified
that will facilitate scale up.
PMID- 28400955
TI - Cost-effectiveness analysis of revised WHO guidelines for management of childhood
pneumonia in 74 Countdown countries.
AB - BACKGROUND: Treatment of childhood pneumonia is a key priority in low-income
countries, with substantial resource implications. WHO revised their guidelines
for the management of childhood pneumonia in 2013. We estimated and compared the
resource requirements, total direct medical cost and cost-effectiveness of
childhood pneumonia management in 74 countries with high burden of child
mortality (Countdown countries) using the 2005 and 2013 revised WHO guidelines.
METHODS: We constructed a cost model using a bottom up approach to estimate the
cost of childhood pneumonia management using the 2005 and 2013 WHO guidelines
from a public provider perspective in 74 Countdown countries. The cost of
pneumonia treatment was estimated, by country, for year 2013, including costs of
medicines and service delivery at three different management levels. We also
assessed country-specific lives saved and disability adjusted life years (DALYs)
averted due to pneumonia treated in children aged below five years. The cost
effectiveness of pneumonia treatment was estimated in terms of cost per DALY
averted by fully implementing WHO treatment guidelines relative to no treatment
intervention for pneumonia. RESULTS: Achieving full treatment coverage with the
2005 WHO guidelines was estimated to cost US$ 2.9 (1.9-4.2) billion compared to
an estimated US$ 1.8 (0.8-3.0) billion for the revised 2013 WHO guidelines in
these countries. Pneumonia management in young children following WHO treatment
guidelines could save up to 39.8 million DALYs compared to a zero coverage
scenario in the year 2013 in the 74 Countdown countries. The median cost
effectiveness ratio per DALY averted in 74 countries was substantially lower for
the 2013 guidelines: US$ 26.6 (interquartile range IQR: 17.7-45.9) vs US$ 38.3
(IQR: US$ 26.2-86.9) per DALY averted for the 2005 guideline respectively.
CONCLUSIONS: Child pneumonia management as detailed in standard WHO guidelines is
a very cost-effective intervention. Implementation of the 2013 WHO guidelines is
expected to result in a 39.5% reduction in treatment costs compared to the 2005
guidelines which could save up to US$ 1.16 (0.68-1.23) billion in the 74
Countdown countries, with potential savings greatest in low HIV burden countries
which can implement effective community case management of pneumonia.
PMID- 28400956
TI - Fukushima after the Great East Japan Earthquake: lessons for developing
responsive and resilient health systems.
AB - BACKGROUND: On 11 March 2011, the Great East Japan Earthquake, followed by a
tsunami and nuclear-reactor meltdowns, produced one of the most severe disasters
in the history of Japan. The adverse impact of this 'triple disaster' on the
health of local populations and the health system was substantial. In this study
we examine population-level health indicator changes that accompanied the
disaster, and discuss options for re-designing Fukushima's health system, and by
extension that of Japan, to enhance its responsiveness and resilience to current
and future shocks. METHODS: We used country-level (Japan-average) or prefecture
level data (2005-2014) available from the portal site of Official Statistics of
Japan for Fukushima, Miyagi, and Iwate, the prefectures that were most affected
by the disaster, to compare trends before (2005-2010) and after (2011-2014) the
'disaster'. We made time-trend line plots to describe changes over time in age
adjusted cause-specific mortality rates in each prefecture. FINDINGS: All three
prefectures, and in particular Fukushima, had lower socio-economic indicators, an
older population, lower productivity and gross domestic product per capita, and
less higher-level industry than the Japan average. All three prefectures were
'medically underserved', with fewer physicians, nurses, ambulance calls and
clinics per 100 000 residents than the Japan average. Even before the disaster,
age-adjusted all-cause mortality in Fukushima was in general higher than the
national rates. After the triple disaster we found that the mortality rate due to
myocardial infarction increased substantially in Fukushima while it decreased
nationwide. Compared to Japan average, spikes in mortality due to lung disease
(all three prefectures), stroke (Iwate and Miyagi), and all-cause mortality
(Miyagi and Fukushima) were also observed post-disaster. The cause-specific
mortality rate from cancer followed similar trends in all three prefectures to
those in Japan as a whole. Although we found a sharp rise in ambulance calls in
Iwate and Miyagi, we did not see such a rise in Fukushima: a finding which may
indicate limited responsiveness to acute demand because of pre-existing
restricted capacity in emergency ambulance services. CONCLUSIONS: We analyze
changes in indicators of health and health systems infrastructure in Fukushima
before and five years following the disaster, and explored health systems'
strengths and vulnerabilities. Spikes in mortality rates for selected non
infectious conditions common among older individuals were observed compared to
the national trends. The results suggest that poorer reserves in the health care
delivery system in Fukushima limited its capacity to effectively meet sudden
unexpected increases in demand generated by the disaster.
PMID- 28400957
TI - Sociodemographic, behavioral, and environmental factors of child mortality in
Eastern Region of Cameroon: results from a social autopsy study.
AB - BACKGROUND: While most child deaths are caused by highly preventable and
treatable diseases such as pneumonia, diarrhea, and malaria, several
sociodemographic, cultural and health system factors work against children
surviving from these diseases. METHODS: A retrospective verbal/social autopsy
survey was conducted in 2012 to measure the biological causes and social
determinants of under-five years old deaths from 2007 to 2010 in Doume,
Nguelemendouka, and Abong-Mbang health districts in the Eastern Region of
Cameroon. The present study sought to identify important sociodemographic and
household characteristics of the 1-59 month old deaths, including the coverage of
key preventive indicators of normal child care, and illness recognition and care
seeking for the children along the Pathway to Survival model. FINDINGS: Of the
635 deceased children with a completed interview, just 26.8% and 11.2% lived in
households with an improved source of drinking water and sanitation,
respectively. Almost all of the households (96.1%) used firewood for cooking, and
79.2% (n = 187) of the 236 mothers who cooked inside their home usually had their
children beside them when they cooked. When 614 of the children became fatally
ill, the majority (83.7%) of caregivers sought or tried to seek formal health
care, but with a median delay of 2 days from illness onset to the decision to
seek formal care. As a result, many (n = 111) children were taken for care only
after their illness progressed from mild or moderate to severe. The main barriers
to accessing the formal health system were the expenses for transportation,
health care and other related costs. CONCLUSIONS: The most common social factors
that contributed to the deaths of 1-59-month old children in the study setting
included poor living conditions, prevailing customs that led to exposure to
indoor smoke, and health-related behaviors such as delaying the decision to seek
care. Increasing caregivers' ability to recognize the danger signs of childhood
illnesses and to facilitate timely and appropriate health care-seeking, and
improving standards of living such that parents or caregivers can overcome the
economic obstacles, are measures that could make a difference in the survival of
the ill children in the study area.
PMID- 28400958
TI - In vitro evaluation of the susceptibility of Acinetobacter baumannii isolates to
antiseptics and disinfectants: comparison between clinical and environmental
isolates.
AB - BACKGROUND: This study aims to assess the susceptibility of Acinetobacter
baumannii isolates to the antiseptics and disinfectants commonly used, and to the
non-approved product. METHODS: This is a prospective study carried out from
February to August 2015, in the Bacteriology department of Mohammed V Military
Teaching hospital of Rabat on A.baumannii isolates collected from colonized
and/or infected patients and environmental samples. The antiseptics and
disinfectants susceptibility testing was assessed using the micromethod validated
in our department. The antiseptics and disinfectants studied were: 70% ethyl
alcohol, chlorhexidine, povidone-iodine, didecyldimethylammonium chloride and a
commercial product which was presented as a hospital disinfectant (non-registered
product). RESULTS: Povidone-iodine, 0.5% chlorhexidine digluconate, 70% ethyl
alcohol and didecyl dimethyl ammonium chloride in combination with N- (3
aminopropyl) -N-dodecylpropane-1, 3-diamine were effective against all the 81
A.baumannii isolates tested, and their logarithmic reduction >= 5 were observed
in 100% of the isolates in their undiluted form. The strains isolated from
patients were more resistant than environmental strains: at a dilution of 1/2 for
70% ethyl alcohol (37.77% vs 11.11%, p = 0.007) and at a dilution of 1/10 (100%
vs 69.44%, p < 0.001) for povidone iodine. The non-registered product was
ineffective with a resistance rate of 96.29% at a dilution of 1/50, 45.67% at a
dilution of 1/10 and 13.58% in its purest form. CONCLUSION: Our study revealed
the effectiveness of the main disinfectants and antiseptics used in Morocco;
three antiseptics tested were effective in their purest form against the 81
A.baumannii isolates. Regarding disinfectants, our results showed an efficacy of
didecyl dimethyl ammonium at the recommended use concentration and in its purest
form. This study emphasizes the need for using disinfectants and antiseptics in
dilutions recommended by the manufacturer because the insufficient dilutions of
these products are not effective. Our findings also demonstrated an inefficiency
of the non-registered product against A.baumanii isolates. However, the non
registered products should be prohibited.
PMID- 28400959
TI - Is a diet low in greenhouse gas emissions a nutritious diet? - Analyses of self
selected diets in the LifeGene study.
AB - BACKGROUND: Climate change is an urgent global issue and the food sector is a
major contributor to greenhouse gas emissions (GHGE). Here we study if a diet low
in GHGE could be a nutritious diet compared to the Nordic Nutrition
Recommendations (NNR). METHODS: The environmental impact of foods from Life Cycle
Assessment (LCA) data was linked to a food frequency questionnaire (FFQ) filled
out by 5,364 participants in the Swedish LifeGene study. Thereafter, we
calculated the daily emission of CO2 equivalents (CO2e) as well as the intake of
selected nutrients associated with vegetables, fruits, meat and dairy products.
The CO2e was divided into quartiles were quartile 1 corresponds to a diet
generating the lowest CO2e, and quartile 4 corresponds to a diet with the highest
CO2e. RESULTS: The overall diet-related emission was 4.7 kg CO2e/day and person,
corresponding to 1.7 ton CO2e/year. In general, there were only small differences
in nutrient intake between groups of varying levels of CO2e, regardless if the
intake was analyzed as absolute intake, energy percent or as nutrient density.
Moreover, adherence to NNR was high for the group with the lowest CO2e, except
for saturated fat where the intake was higher than recommended for all CO2e
groups. On the other hand, only the group with the lowest CO2e fulfilled
recommended intake of fiber. However, none of the CO2e groups reached the
recommended intake of folate and vitamin D. CONCLUSIONS: Here we show that a self
selected diet low in CO2e provides comparable intake of nutrients as a diet high
in in CO2e.
PMID- 28400960
TI - Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates
with histological evaluation in mice.
AB - BACKGROUND: The intratracheal instillation of bleomycin in mice induces early
damage to alveolar epithelial cells and development of inflammation followed by
fibrotic tissue changes and represents the most widely used model of pulmonary
fibrosis to investigate human IPF. Histopathology is the gold standard for
assessing lung fibrosis in rodents, however it precludes repeated and
longitudinal measurements of disease progression and does not provide information
on spatial and temporal distribution of tissue damage. Here we investigated the
use of the Micro-CT technique to allow the evaluation of disease onset and
progression at different time-points in the mouse bleomycin model of lung
fibrosis. Micro-CT was throughout coupled with histological analysis for the
validation of the imaging results. METHODS: In bleomycin-instilled and control
mice, airways and lung morphology changes were assessed and reconstructed at
baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft
score, percentage of collagen content and percentage of alveolar air area were
detected on lung slides processed by histology and subsequently compared with
Micro-CT parameters. RESULTS: Extent (%) of fibrosis measured by Micro-CT
correlated with Ashcroft score, the percentage of collagen content and the
percentage of alveolar air area (r2 = 0.91; 0.77; 0.94, respectively). Distal
airway radius also correlated with the Ashcroft score, the collagen content and
alveolar air area percentage (r2 = 0.89; 0.78; 0.98, respectively). CONCLUSIONS:
Micro-CT data were in good agreement with histological read-outs as micro-CT was
able to quantify effectively and non-invasively disease progression
longitudinally and to reduce the variability and number of animals used to assess
the damage. This suggests that this technique is a powerful tool for
understanding experimental pulmonary fibrosis and that its use could translate
into a more efficient drug discovery process, also helping to fill the gap
between preclinical setting and clinical practice.
PMID- 28400961
TI - Effect of shift work on hypertension: cross sectional study.
AB - BACKGROUND: The need of efficient resource management and full-time accessibility
to resources has increased with the development of industry, resulting in the
increase of shift workers. Previous researches of past decades show that there
are various health effects on shift workers. However, the definition and the form
of shift work have varied from each research and occupational harmful factors
except for shift work have not been excluded completely in previous researches.
Therefore, in this research, we tried to find out the effect of shift work
focusing on the hypertension. To complement previously mentioned weakness of
other researches, we performed our research on participants to whom we could
minimize other risk factors excluding shift work. METHODS: This research examined
1,953 petrochemical plant male workers (shift work 1,075, day worker 878) who did
medical checkup from 1st Jan. 2014 to 31th Dec. 2014 in a general hospital
located in Ulsan, based on their medical records and questionnaires. With the
questionnaire, we found out their basic information including age, social status,
occupational history, and we took their physical measurements. RESULTS: Compared
to day workers, shift workers' odds ratio of developing hypertension was 1.31
(95% CI 0.98-1.75). After adjusting confounding variables, adjusted odds ratio
for entire subjects was 1.51 (95% CI 1.11-2.06). Also, for subjects who were in
continuous service for over 20 years, odds ratio was 1.51 (95% CI 1.08-2.11).
CONCLUSIONS: Shift workers had a higher chance of hypertension than day workers
do. Particularly, the longer the workers work continuously, the risk of
hypertension getting higher.
PMID- 28400962
TI - Epistemic injustice in psychiatry.
AB - It has been argued that those who suffer from medical conditions are more
vulnerable to epistemic injustice (a harm done to a person in their capacity as
an epistemic subject) than healthy people. This editorial claims that people with
mental disorders are even more vulnerable to epistemic injustice than those with
somatic illnesses. Two kinds of contributory factors are outlined, global and
specific. Some suggestions are made to counteract the effects of these factors,
for instance, we suggest that physicians should participate in groups where the
subjective experience of patients is explored, and learn to become more aware of
their own unconscious prejudices towards psychiatric patients.
PMID- 28400963
TI - Psychiatry and the geriatric syndromes - creating constructive interfaces.
AB - Integrating mental and physical healthcare is difficult to achieve because of
professional and organisational barriers. Psychiatrists recognise the problems
resulting from fragmentation of services and want continuity of care for
patients, but commissioning and service structures perpetuate these problems. One
way forward may be to follow the syndromic model employed by geriatricians as a
means of avoiding over-emphasis on diagnosis above the pragmatics of implementing
multi-component, coordinated care. Commissioners need to be made aware of the
overlap and complementarity of skills possessed by old age psychiatry and
geriatric medicine to create joint services for people vulnerable to dementia and
delirium. A re-forged alliance between the two specialties will be necessary to
turn integrated care for frail, elderly people from rhetoric into reality.
PMID- 28400964
TI - Police liaison and section 136: comparison of two different approaches.
AB - Aims and method Two police liaison and section 136 schemes were developed
alongside police services at different sites within the same NHS trust. In one, a
mental health nurse worked with frontline police attending incidents related to
mental health. The other involved nurses providing advice from the police control
room. Section 136 detentions were measured over two 6-month periods (6 months
apart) before and after practice change. Data analysed included total numbers of
section 136 assessments, outcomes following subsequent assessment, and relevant
diagnostic and demographic factors. Association of any change in section 136
total numbers and proportion subsequently admitted was investigated in both
sites. Results The model involving a nurse alongside frontline police showed
significant reduction in section 136 numbers (38%, P < 0.01) as well as greater
admission rates (P = 0.01). The scheme involving support within the police
control room did not show any change in section 136 detention but showed a non
significant (P = 0.16) decrease in subsequent admission. Clinical implications
Mental health nurses working alongside frontline police officers can help improve
section 136 numbers and outcomes.
PMID- 28400965
TI - Online media reporting of suicides: analysis of adherence to existing guidelines.
AB - Aims and method To assess the compliance of contemporary online media output with
guidelines for the responsible reporting of suicidal acts. A search engine was
used to identify online media reports of suicide from UK sources over the course
of 1 month. Each article was assessed against guidelines for the responsible
reporting of suicide produced by the Samaritans, a UK mental health charity.
Results We identified 229 articles, of which 199 failed to comply with at least
one of the Samaritans' guidelines. Failure to mention support sources, excessive
detail about the method used and undue speculation about the trigger for suicide
were the most commonly breached guidelines. Significant differences were found
between the quality of local and national media sources, with local media sources
being broadly more compliant with guidelines. Clinical implications This study
highlights the urgent need for the implementation of responsible reporting
guidelines in online media articles as a component of suicide prevention efforts.
PMID- 28400966
TI - Caregiver burden and distress following the patient's discharge from psychiatric
hospital.
AB - Aims and method Caring for someone with a mental illness is increasingly
occurring within the community. As a result, family members who fulfil a
caregiving role may experience substantial levels of burden and psychological
distress. This study investigates the level of burden and psychological distress
reported by caregivers after the patient's admission. Results This study found
that the overall level of burden and psychological distress experienced by
caregivers did not differ according to the patient's legal status. However, the
caregivers of those who were voluntarily admitted supervised the person to a
significantly greater extent than the caregivers of those who were involuntarily
admitted. Approximately 15% of caregivers revealed high levels of psychological
distress. Clinical implications This study may emphasise a need for mental health
professionals to examine the circumstances of caregivers, particularly of those
caring for patients who are voluntarily admitted, a year after the patient's
admission.
PMID- 28400967
TI - Unlocking an acute psychiatric ward: the impact on unauthorised absences,
assaults and seclusions.
AB - Aims and method The acute psychiatric in-patient service in Christchurch, New
Zealand, recently changed from two locked and two unlocked wards to four open
wards. This provided the opportunity to evaluate whether shifting to an unlocked
environment was associated with higher rates of adverse events, including
unauthorised absences, violent incidents and seclusion. We compared long-term
adverse event data before and after ward configuration change. Results Rates of
unauthorised absences increased by 58% after the change in ward configuration (P
= 0.005), but seclusion hours dropped by 53% (P = 0.001). A small increase in
violent incidents was recorded but this was not statistically significant.
Clinical implications Although unauthorised absences increased, the absence of
statistically significant changes for violent incidents and a reduction in
seclusion hours suggest that the change to a less restrictive environment may
have some positive effects.
PMID- 28400968
TI - Psychiatry trainees' experiences of cognitive-behavioural therapy training in a
UK deanery: a qualitative analysis.
AB - Aims and method To explore core psychiatry trainees' experiences of cognitive
behavioural therapy (CBT) training by using interpretative phenomenological
analysis of semi-structured interviews conducted with seven core trainee
psychiatrists in Yorkshire and the Humber Deanery. Results Four key themes
emerged: (1) barriers to training; (2) guidance, with emphasis on the importance
of supervision groups; (3) acquisition of new skills and confidence; (4) personal
influence on the training experience. Clinical implications Many trainees in
Yorkshire have a positive experience of CBT training; however, some also
experience barriers to acquiring the relevant skills. Further research should
build on the positive factors and barriers identified here, with a view to
guiding improvements in training nationwide.
PMID- 28400969
TI - Antipsychotic prescribing of consultant forensic psychiatrists working in
different levels of secure care with patients with schizophrenia.
AB - Aims and method To detect any differences in the antipsychotic prescribing
practices of consultant forensic psychiatrists working in different levels of
secure care with patients diagnosed with schizophrenia, and to identify potential
reasons for any differences. Prescribing data were collected from four secure
hospitals within one National Health Service trust. A questionnaire was sent to
consultant forensic psychiatrists working at those hospitals as well as those
working in the trust's community forensic services. Results Consultants working
in high security prescribed more oral antipsychotics than consultants working in
medium and low security, who prescribed more depot antipsychotics, as established
via the prescribing data. The questionnaire provided insight regarding the
reasons for these preferences. Clinical implications There were differences in
the antipsychotic prescribing practices of consultant forensic psychiatrists
working in different levels of secure care, and, overall, the rate of depot
antipsychotic prescribing was lower than might be expected. Although it was
positive that the rate of polypharmacy was low when compared with earlier
studies, the lower-than-expected rate of depot antipsychotic prescribing has
clinical implications.
PMID- 28400970
TI - Niemann-Pick type C disease - the tip of the iceberg? A review of
neuropsychiatric presentation, diagnosis and treatment.
AB - Niemann-Pick type C (NP-C) disease is a rare neurodegenerative lysosomal storage
disorder. It is highly heterogeneous, and there is limited awareness of a
substantial subgroup that has an attenuated adolescent/adult-onset disease. In
these patients psychiatric features, often a psychosis, may dominate the initial
impression, although often there is an associated ataxia and cognitive
impairment. Typically, patients experience a substantial diagnostic delay. In
this review we highlight the importance of early recognition and discuss the
pathophysiology, neuropsychiatric presentation and recent changes in the
investigation and work-up of these patients, and treatment options.
PMID- 28400971
TI - The mini-PAT as a multi-source feedback tool for trainees in child and adolescent
psychiatry: assessing whether it is fit for purpose.
AB - This paper discusses the research supporting the use of multi-source feedback
(MSF) for doctors and describes the mini-Peer Assessment Tool (mini-PAT), the MSF
instrument currently used to assess trainees in child and adolescent psychiatry.
The relevance of issues raised in the literature about MSF tools in general is
examined in relation to trainees in child and adolescent psychiatry as well as
the appropriateness of the mini-PAT for this group. Suggestions for change
including modifications to existing MSF tools or the development of a specialty
specific MSF instrument are offered.
PMID- 28400972
TI - The writings of Thomas Szasz.
PMID- 28400973
TI - Critical reflections on psychiatry: could Thomas Szasz still have relevance in
modern medical practice?
PMID- 28400974
TI - Understanding challenges around implementation of specialist service
recommendations for obsessive-compulsive disorder.
PMID- 28400975
TI - Antipathy towards people with personality disorders.
PMID- 28400977
TI - Fragile X Syndrome: Lessons Learned from the Most Translated Neurodevelopmental
Disorder in Clinical Trials.
AB - Fragile X syndrome (FXS) is the leading genetic cause of autism spectrum disorder
(ASD) and inherited intellectual disability (ID) worldwide. Preclinical successes
in understanding the biology of FXS have led to numerous translational attempts
in human clinical trials of therapeutics that target the excitatory/inhibitory
neural signaling imbalances thought to underlie FXS. Despite the preclinical
success story, the negative results of the human clinical trials have been deemed
to be at least in part disappointing by the field. In this commentary, we contend
that such negative studies results in clinical trials may actually propel the FXS
field forward by serving as important lessons for designing and implementing
improved future clinical trials such that can objectively assess the full range
of responses to new therapeutics.
PMID- 28400976
TI - ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy.
AB - Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children
and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1
(SMN1) gene. SMN2, a nearly identical copy of SMN1, cannot compensate for the
loss of SMN1 due to predominant skipping of exon 7. While various regulatory
elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing
silencer N1 (ISS-N1) has emerged as the most promising target thus far for
antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring
exclusive license from the University of Massachussets Medical School in 2010,
Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development
of SpinrazaTM (synonyms: Nusinersen, IONIS-SMNRX, ISIS-SMNRX), an antisense drug
based on ISS-N1 target. SpinrazaTM showed very promising results at all steps of
the clinical development and was approved by US Food and Drug Administration
(FDA) on December 23, 2016. SpinrazaTM is the first FDA-approved treatment for
SMA and the first antisense drug to restore expression of a fully functional
protein via splicing correction. The success of SpinrazaTM underscores the
potential of intronic sequences as promising therapeutic targets and sets the
stage for further improvement of antisense drugs based on advanced
oligonucleotide chemistries and delivery protocols.
PMID- 28400978
TI - Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status
Epilepticus Rat Model.
AB - AIM: Status epilepticus (SE) results in the generation of reactive oxygen species
(ROS), which contribute to seizure-induced brain injury. It is well known that
oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone
(TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil
that has anti-inflammatory, anti-cancer, and antioxidant activity in various
diseases. This study evaluated the protective effects of TQ on brain injury in a
lithium-pilocarpine rat model of SE and investigated the underlying mechanism
related to antioxidative pathway. METHODS: Electroencephalogram and Racine scale
were used to value seizure severity. Passive-avoidance test was used to determine
learning and memory function. Moreover, anti-oxidative activity of TQ was
observed using Western blot and super oxide dismutase (SOD) activity assay.
RESULTS: Latency to SE increased in the TQ-pretreated group compared with rats in
the model group, while the total power was significantly lower. Seizure severity
measured on the Racine scale was significantly lower in the TQ group compared
with the model group. Results of behavioral experiments suggest that TQ may also
have a protective effect on learning and memory function. Investigation of the
protective mechanism of TQ showed that TQ-pretreatment significantly increased
the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. CONCLUSION:
These findings showed that TQ attenuated brain injury induced by SE via an anti
oxidative pathway.
PMID- 28400979
TI - Depression, Diabetes and Dementia: Formaldehyde May Be a Common Causal Agent;
Could Carnosine, a Pluripotent Peptide, Be Protective?
PMID- 28400980
TI - Association between Coagulation Function and Cerebral Microbleeds in Ischemic
Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease.
AB - Cerebral microbleeds (CMBs), which indicate hemorrhage-prone disease, may
associate with hemostatic abnormalities, but the association between CMBs and
coagulation function is uncertain. We aimed to examine this possible association.
The following coagulation function indicators were evaluated in 85 consecutive
ischemic stroke patients diagnosed with atrial fibrillation and/or rheumatic
heart disease: prothrombintime (PT), activated partial thromboplastin time
(APTT), and levels of D-dimer and fibrinogen. Indicators were assessed within 24
h after admission. CMBs were identified based on published criteria by two
experienced stroke neurologists working independently. PT, APPT, and levels of D
dimer and fibrinogen were compared between patients with and without CMBs using
univariate and multivariate analysis. CMBs were detected in 48 patients (56.5%),
and fibrinogen levels in these patients were independently and significantly
higher than in patients without CMBs after adjustment (OR 2.16, 95% CI 1.20-3.90,
P=0.01), whereas the two types of patients did not differ significantly in PT,
APPT, or D-dimer levels. The presence of CMBs in ischemic stroke patients with
atrial fibrillation and/or rheumatic heart disease is associated with elevated
levels of fibrinogen. Larger prospective studies are needed to verify this
association and explore the mechanisms involved.
PMID- 28400981
TI - New Developments in the Pathophysiology, Workup, and Diagnosis of Dural Venous
Sinus Thrombosis (DVST) and a Systematic Review of Endovascular Treatments.
AB - Dural venous sinus thrombosis (DVST) is a rare cause of stroke, which typically
affects young women. The importance of identifying pre-disposing factors that
lead to venous stasis lies in the foundation of understanding the etiology,
pathophysiology and clinical presentation. The precise therapeutic role of
interventional therapies is not fully understood though the current data do
suggest potential applications. The aim of the study was to perform a systematic
review and meta-analysis to evaluate the utility of and short-term 30-day
survival after endovascular therapy for patients with DVST. Standard PRISMA
guidelines were followed. Data sources included PubMed keywords and phrases,
which were also incorporated into a MeSH search to yield articles indexed in
Medline over a 5-year period. All RCTs, observational cohort studies, and
administrative registries comparing or reporting DVST were included. Sixty-six
studies met inclusion criteria. 35 articles investigating treatment in a
summation of 10,285 patients were eligible for data extraction and included in
the review of treatment modalities. A total of 312 patients were included for
statistical analysis. All patients included received endovascular intervention
with direct thrombolysis, mechanical thrombectomy or both. 133 (42.6%) patients
were documented to have a neurologic decline, which prompted endovascular
intervention. All patients who had endovascular interventions were those who were
started on and failed systemic anticoagulation. 44 patients were reported to have
intracranial hemorrhages after intervention. Regardless of systemic
anticoagulation, patients were still reported to have complications of VTE and
PE. Primary outcome at 3-6 month follow up revealed mRS<1 in 224 patients. DVST
presents with many diagnostic and therapeutic challenges. The utility of invasive
interventions such as local thrombolysis and mechanical thrombectomy is not fully
understood. It is exceedingly difficult to conduct large randomized trials for
this low incidence disease process with large pathophysiological heterogeneity.
PMID- 28400983
TI - Allergy and Aging: An Old/New Emerging Health Issue.
AB - Allergy reactions are the most common immunological diseases and represent one of
the most widespread and fast growing chronic human health problems among people
over 15 years of age in developed countries. As populations get older worldwide,
allergy manifestations in aged persons will occur more often in the future. To
date, there has been much more studies on allergies in children than in adults.
As the population ages, clinicians must be prepared to meet all the elderly's
health care needs, including these new and emerging health issue. Allergic
diseases represent an old/new emerging health issue. Because many common
illnesses masquerade as atopic disease, the differential diagnosis of suspected
allergic diseases becomes more expanded in an aging population. Research in the
field needs to focus on both human and animal model systems to investigate the
impact of the aging process on the immunologic pathways underpinning allergy and
its different facets.
PMID- 28400982
TI - Shining the Light on Senescence Associated LncRNAs.
AB - Cellular senescence can be described as a complex stress response that leads to
irreversible cell cycle arrest. This process was originally described as an event
that primary cells go through after many passages of cells during cell culture.
More recently, cellular senescence is viewed as a programmed process by which the
cell displays a senescence phenotype when exposed to a variety of stresses.
Cellular senescence has been implicated in tumor suppression and aging such that
senescence may contribute to both tumor progression and normal tissue repair.
Here, we review different forms of cellular senescence, as well as current
biomarkers used to identify senescent cells in vitro and in vivo. Additionally,
we highlight the role of senescence-associated long noncoding RNAs (lncRNAs).
PMID- 28400984
TI - Is Technology Present in Frailty? Technology a Back-up Tool for Dealing with
Frailty in the Elderly: A Systematic Review.
AB - This study analyzes the technologies used in dealing with frailty within the
following areas: prevention, care, diagnosis and treatment. The aim of this paper
is, on the one hand, to analyze the extent to which technology is present in
terms of its relationship with frailty and what technological resources are used
to treat it. Its other purpose is to define new challenges and contributions made
by physiotherapy using technology. Eighty documents related to research,
validation and/or the ascertaining of different types of hardware, software or
both were reviewed in prominent areas. The authors used the following scales: in
the area of diagnosis, Fried's phenotype model of frailty and a model based on
trials for the design of devices. The technologies developed that are based on
these models accounted for 55% and 45% of cases respectively. In the area of
prevention, the results proved similar regarding the use of wireless sensors with
cameras (35.71%), and KinectTM sensors (28.57%) to analyze movements and postures
that indicate a risk of falling. In the area of care, results were found
referring to the use of different motion, physiological and environmental
wireless sensors (46,15%), i.e. so-called smart homes. In the area of treatment,
the results show with a percentage of 37.5% that the Nintendo(r) WiiTM console is
the most used tool for treating frailty in elderly persons. Further work needs to
be carried out to reduce the gap existing between technology, frail elderly
persons, healthcare professionals and carers to bring together the different
views about technology. This need raises the challenge of developing and
implementing technology in physiotherapy via serious games that may via play and
connectivity help to improve the functional capacity, general health and quality
of life of frail individuals.
PMID- 28400985
TI - Spanning from the West to East: An Updated Review on Endovascular Treatment of
Intracranial Atherosclerotic Disease.
AB - Ischemic stroke is a major cause of morbidity and mortality, incurring
significant cost. Intracranial atherosclerotic disease (ICAD) accounts for 10-15%
of ischemic stroke in Western societies, but is an underlying pathology in up to
54% of ischemic strokes in Asian populations. ICAD has largely been treated with
medical management, although a few studies have examined outcomes following
endovascular treatment. Our objective was to summarize the major trials that have
been performed thus far in regard to the endovascular treatment of ICAD and to
provide direction for future management of this disease process. Systematic
review of the literature from 1966 to 2015, was conducted in regard to
intracranial angioplasty and stenting. Studies were analyzed from PubMed,
American Heart Association and Society of Neurointerventional Surgery databases.
SAMMPRIS and VISSIT are the only randomized controlled trials from which Western
guidelines of intracranial stenting have been derived, which have displayed the
superiority of medical management. However, pooled reviews of smaller studies and
other nonrandomized trials have shown better outcomes with endovascular therapy
in select patient subsets, such as intracranial vertebrobasilar stenosis or in
the presence of robust collaterals. Suboptimal cases, including longer lesions,
bifurcations and significant tortuosity tend to fair better with medical
management. Medical management has been shown to be more efficacious with less
adverse outcomes than endovascular therapy. However, the majority of studies on
endovascular management included a diverse patient population without ideal
selection criteria, resulting in higher adverse outcomes. Population analyses and
selective utilization of endovascular therapy have shown that the treatment may
be superior to other management in select patients.
PMID- 28400986
TI - Combining Injectable Plasma Scaffold with Mesenchymal Stem/Stromal Cells for
Repairing Infarct Cavity after Ischemic Stroke.
AB - Stroke survivors are typically left with structural brain damage and associated
functional impairment in the chronic phase of injury, for which few therapeutic
options exist. We reported previously that transplantation of human embryonic
stem cell (hESC)-derived neural stem cells together with Matrigel scaffolding
into the brains of rats after focal ischemia reduced infarct volume and improved
neurobehavioral performance. Matrigel is a gelatinous protein mixture extracted
from mouse sarcoma cells, thus would not be approved for use as a scaffold
clinically. In this study, we generated a gel-like scaffold from plasma that was
controlled by changing the concentration of CaCl2. In vitro study confirmed that
10-20 mM CaCl2 and 10-40% plasma did not affect the viability and proliferation
of human and rat bone marrow mesenchymal stem/stromal cells (BMSCs) and neural
stem cells (NSCs). We transplanted plasma scaffold in combination of BMSCs into
the cystic cavity after focal cerebral ischemia, and found that the atrophy
volume was dramatically reduced and motor function was significantly improved in
the group transplanted with scaffold/BMSCs compared with the groups treated with
vehicle, scaffold or BMSCs only. Our data suggest that plasma-derived scaffold in
combination of BMSCs is feasible for tissue engineering approach for the stroke
treatment.
PMID- 28400988
TI - The Delta133p53 Isoform Reduces Wtp53-induced Stimulation of DNA Pol gamma
Activity in the Presence and Absence of D4T.
AB - : The mitochondrial toxicity of nucleoside reverse transcriptase inhibitors
(NRTIs) is due to the inhibition of mitochondrial DNA (mtDNA) polymerase gamma
(pol gamma). Previous studies have shown that wild type p53 (wtp53) can interact
with pol gamma and mtDNA to enhance mitochondrial DNA base excision repair
(mtBER) activity and increase the accuracy of DNA synthesis. The N-terminal
transactivation domain and central specific DNA-binding domain of p53 play
critical roles in the stimulation of BER. In this study, we identified the
possible roles of wtp53, Delta40p53 and Delta133p53 in regulating mtDNA pol gamma
activity in cells with d4T treatment. The results show that Delta40p53 and
Delta133p53 can exist in mitochondrial fragments and form polymers with
themselves or wtp53. Unlike wtP53, Delta133p53 alone cannot increase DNA pol
gamma activity. More importantly, we found that Delta133p53 played a negative
role in p53 stimulation of DNA pol gamma activity when studied in d4T-treated and
d4T-untreated mitochondrial extracts. Gel shift data also indicate that
Delta40p53 and Delta133p53 cannot interact with APE. Wtp53 and Delta40p53 can act
antagonize the effect of d4T inhibition of DNA pol gamma activity. However, when
wtp53 interacted with Delta133p53, DNA pol gamma activity was significantly
decreased. CONCLUSION: Delta133p53 negatively regulates p53's stimulation of pol
gamma in the presence and absence of d4T.
PMID- 28400987
TI - Serum Hepcidin Levels, Iron Dyshomeostasis and Cognitive Loss in Alzheimer's
Disease.
AB - This pilot study examined the status of the master iron regulatory peptide,
hepcidin, and peripheral related iron parameters in Alzheimer's disease (AD) and
mild cognitive impairment patients, and evaluated the relationship between iron
dyshomeostasis and amyloid-beta (Abeta), cognitive assessment tests, neuroimaging
and clinical data. Frozen serum samples from the Oregon Tissue Bank were used to
measure serum levels of hepcidin, ferritin, Abeta40, Abeta42 using enzyme-linked
immunosorbent assay. Serum transferrin levels were determined indirectly as total
iron binding capacity, serum iron was measured and the percent saturation of
transferrin calculated. The study variables were correlated with the patients'
existing cognitive assessment tests, neuroimaging, and clinical data. Hepcidin,
and iron-related proteins tended to be higher in AD patients than controls,
reaching statistical significance for ferritin, whereas Abeta40, Abeta42 serum
levels tended to be lower. Patients with pure AD had three times higher serum
hepcidin levels than controls; gender differences in hepcidin and iron-related
proteins were observed. Patient stratification based on clinical dementia rating
sum of boxes revealed significantly higher levels of iron and iron-related
proteins in AD patients in the upper 50% as compared to controls, suggesting that
iron dyshomeostasis worsens as cognitive impairment increases. Unlike Abeta
peptides, iron and iron-related proteins showed significant association with
cognitive assessment tests, neuroimaging, and clinical data. Hepcidin and iron
related proteins comprise a group of serum biomarkers that relate to AD diagnosis
and AD disease progression. Future studies should determine whether strategies
targeted to diminishing hepcidin synthesis/secretion and improving iron
homeostasis could have a beneficial impact on AD progression.
PMID- 28400989
TI - Serum Leptin Concentration is Associated with Incident Frailty in Older Adults.
AB - Obesity has been associated with higher risk of frailty in older adults, but the
pathophysiological mechanisms are unclear. No previous study has examined the
association between leptin, an adipokine, and the risk of frailty in older
adults, and whether this association could be explained by insulin resistance or
chronic inflammation. Data were taken from 1,573 individuals without diabetes
mellitus, aged >=60 years, from the Seniors-ENRICA cohort. In 2008-2010, leptin,
the homeostasis model assessment of insulin resistance (HOMA-IR) and C-reactive
protein (CRP) were measured. Study participants were followed-up through 2012 to
assess incident frailty, defined as at least two of the following Fried criteria:
exhaustion, weakness, low physical activity, and slow walking speed. Analyses
were performed with logistic regression and adjusted for the main confounders.
Over a median follow-up of 3.5 years, 280 cases of incident frailty were
identified. Compared to individuals in the lowest tertile of serum leptin, those
in the highest tertile showed an increased risk of frailty (odds ratio [OR]:
2.12; 95% confidence interval [CI]: 1.47-3.06; p-trend <0.001). Further
adjustment for the percentage of body fat led to an OR of 1.69 (95% CI: 1.11
2.61; p-trend=0.01). After additional adjustment for HOMA-IR and CRP, the OR for
frailty was 1.59 (95% CI: 1.01-2.52; p-trend=0.04). Results did not vary
according to sex, abdominal obesity or the percentage of body fat. Being in the
highest versus lowest tertile of leptin was associated with increased risk of
exhaustion (OR: 2.16; 95% CI: 1.32-3.55; p-trend=0.001) and muscle weakness (OR:
1.77; 95% CI: 1.25-2.51; p-trend=0.001), in the analyses adjusted for potential
confounders and body fat. Higher leptin concentration was associated with greater
risk of frailty in older adults. This association was only modestly explained by
insulin resistance and chronic inflammation, as measured by CRP.
PMID- 28400990
TI - Classifications of Multispectral Colorectal Cancer Tissues Using Convolution
Neural Network.
AB - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer among men and
women. Its diagnosis in early stages, typically done through the analysis of
colon biopsy images, can greatly improve the chances of a successful treatment.
This paper proposes to use convolution neural networks (CNNs) to predict three
tissue types related to the progression of CRC: benign hyperplasia (BH),
intraepithelial neoplasia (IN), and carcinoma (Ca). METHODS: Multispectral biopsy
images of thirty CRC patients were retrospectively analyzed. Images of tissue
samples were divided into three groups, based on their type (10 BH, 10 IN, and 10
Ca). An active contour model was used to segment image regions containing
pathological tissues. Tissue samples were classified using a CNN containing
convolution, max-pooling, and fully-connected layers. Available tissue samples
were split into a training set, for learning the CNN parameters, and test set,
for evaluating its performance. RESULTS: An accuracy of 99.17% was obtained from
segmented image regions, outperforming existing approaches based on traditional
feature extraction, and classification techniques. CONCLUSIONS: Experimental
results demonstrate the effectiveness of CNN for the classification of CRC tissue
types, in particular when using presegmented regions of interest.
PMID- 28400991
TI - Computer Science, Biology and Biomedical Informatics academy: Outcomes from 5
years of Immersing High-school Students into Informatics Research.
AB - The University of Pittsburgh's Department of Biomedical Informatics and Division
of Pathology Informatics created a Science, Technology, Engineering, and
Mathematics (STEM) pipeline in 2011 dedicated to providing cutting-edge
informatics research and career preparatory experiences to a diverse group of
highly motivated high-school students. In this third editorial installment
describing the program, we provide a brief overview of the pipeline, report on
achievements of the past scholars, and present results from self-reported
assessments by the 2015 cohort of scholars. The pipeline continues to expand with
the 2015 addition of the innovation internship, and the introduction of a program
in 2016 aimed at offering first-time research experiences to undergraduates who
are underrepresented in pathology and biomedical informatics. Achievements of
program scholars include authorship of journal articles, symposium and summit
presentations, and attendance at top 25 universities. All of our alumni
matriculated into higher education and 90% remain in STEM majors. The 2015 high
school program had ten participating scholars who self-reported gains in
confidence in their research abilities and understanding of what it means to be a
scientist.
PMID- 28400992
TI - Implementation of a Software Application for Presurgical Case History Review of
Frozen Section Pathology Cases.
AB - BACKGROUND: The frozen section pathology practice at Mayo Clinic in Rochester
performs ~20,000 intraoperative consultations a year (~70-80/weekday). To prepare
for intraoperative consultations, surgical pathology fellows and residents review
the case history, previous pathology, and relevant imaging the day before
surgery. Before the work described herein, review of pending surgical pathology
cases was a paper-based process requiring handwritten transcription from the
electronic health record, a laborious and potentially error prone process.
METHODS: To facilitate more efficient case review, a modular extension of an
existing surgical listing software application (Surgical and Procedure Scheduling
[SPS]) was developed. The module (SPS-pathology-specific module [PM]) added
pathology-specific functionality including recording case notes, prefetching of
radiology, pathology, and operative reports from the medical record, flagging
infectious cases, and real-time tracking of cases in the operating room. After
implementation, users were surveyed about its impact on the surgical pathology
practice. RESULTS: There were 16 survey respondents (five staff pathologists and
eleven residents or fellows). All trainees (11/11) responded that the application
improved an aspect of surgical list review including abstraction from medical
records (10/11), identification of possibly infectious cases (7/11), and speed of
list preparation (10/11). The average reported time savings in list preparation
was 1.4 h/day. Respondents indicated the application improved the speed (11/16),
clarity (13/16), and accuracy (10/16) of morning report. During the workday,
respondents reported the application improved real-time case review (14/16) and
situational awareness of ongoing cases (13/16). CONCLUSIONS: A majority of
respondents found the SPS-PM improved all preparatory and logistical aspects of
the Mayo Clinic frozen section surgical pathology practice. In addition, use of
the SPS-PM saved an average of 1.4 h/day for residents and fellows engaged in
preparatory case review.
PMID- 28400993
TI - Criteria to Screen Molecular Tests for the Diagnosis of Herpes Simplex Virus in
the Central Nervous System have no Propensity to Harm.
AB - OBJECTIVES: Investigators have ruled out herpes simplex virus (HSV) infection
without the detection of herpes simplex deoxyribonucleic acid in cerebrospinal
fluid (CSF) (i.e., HSV polymerase chain reaction [PCR]) by laboratory (normal CSF
white blood cell count and protein) and clinical criteria (age >=2 years, no
history of human immunodeficiency virus or solid-organ transplant). Compared to
HSV PCR of all samples, the algorithm saves money in test costs and may decrease
exposure to acyclovir by illustrating the low probability that the patient has
HSV. Concern exists that algorithm use may cause harm through alteration of
empiric acyclovir treatment in patients with true HSV central nervous system
infection. METHODS: All Department of Veterans Affair's patients with a positive
HSV PCR of the CSF between 2000 and 2013 were identified and their medical
records reviewed to determine the extent and possible impact of omitted HSV PCR
testing by the algorithm. RESULTS: Of 6357 total results, 101 patients had a
positive CSF HSV PCR in the study period. Among the positive CSF HSV PCR results,
the algorithm excluded 7 (7%) from PCR testing. Record review indicated these
seven patients not tested by the algorithm with a positive CSF HSV PCR were
considered by their attending physician not to have active HSV. CONCLUSION: The
algorithm to screen HSV tests had no propensity to harm.
PMID- 28400994
TI - Pathological Diagnosis of Gastric Cancers with a Novel Computerized Analysis
System.
AB - BACKGROUND: Recent studies of molecular biology have provided great advances for
diagnostic molecular pathology. Automated diagnostic systems with computerized
scanning for sampled cells in fluids or smears are now widely utilized. Automated
analysis of tissue sections is, however, very difficult because they exhibit a
complex mixture of overlapping malignant tumor cells, benign host-derived cells,
and extracellular materials. Thus, traditional histological diagnosis is still
the most powerful method for diagnosis of diseases. METHODS: We have developed a
novel computer-assisted pathology system for rapid, automated histological
analysis of hematoxylin and eosin (H and E)-stained sections. It is a multistage
recognition system patterned after methods that human pathologists use for
diagnosis but harnessing machine learning and image analysis. The system first
analyzes an entire H and E-stained section (tissue) at low resolution to search
suspicious areas for cancer and then the selected areas are analyzed at high
resolution to confirm the initial suspicion. RESULTS: After training the
pathology system with gastric tissues samples, we examined its performance using
other 1905 gastric tissues. The system's accuracy in detecting malignancies was
shown to be almost equal to that of conventional diagnosis by expert
pathologists. CONCLUSIONS: Our novel computerized analysis system provides a
support for histological diagnosis, which is useful for screening and quality
control. We consider that it could be extended to be applicable to many other
carcinomas after learning normal and malignant forms of various tissues.
Furthermore, we expect it to contribute to the development of more objective
grading systems, immunohistochemical staining systems, and fluorescent-stained
image analysis systems.
PMID- 28400995
TI - WhatsApp for Teaching Pathology Postgraduates: A Pilot Study.
AB - INTRODUCTION: Postgraduate students spend a sizeable proportion of their time on
social media platforms such as WhatsApp and Facebook. This change in our social
interaction needs to be accommodated in our teaching methods. To engage them and
arouse their curiosity, WhatsApp is an ideal platform. Digital photography by
cell phone cameras has made it possible to share cases and discuss them with
students round the clock. OBJECTIVE: The primary aim of the study was to develop
sharing and discussion of images using WhatsApp. It also aimed at gathering
feedback by means of a questionnaire from pathology residents about their views
about the use of WhatsApp for teaching purpose. MATERIALS AND METHODS: A WhatsApp
group by the name "Pathology on the Go" was created with the authors of this
study as group administrators and all junior and senior resident doctors (69) as
members. The group was used to discuss interesting cases, quiz questions, and
other pathology-related academic issues. At the end of 4 weeks, a questionnaire
was distributed among the members, and feedback was sought regarding their
experience in the group. RESULTS: Over a 4-week period, 16 cases were discussed
with 647 posts. A total of 45 participants out of 69 were active participants,
and they had an average of 14 posts over the 4-week period. Majority of the
participants found the discussions very useful with minimal disruption of the
daily routine. CONCLUSION: There is a need to incorporate Web 2.0 tools such as
WhatsApp in our teaching methods to capture as much screen time of the students
as possible.
PMID- 28400996
TI - Open-source Software for Demand Forecasting of Clinical Laboratory Test Volumes
Using Time-series Analysis.
AB - BACKGROUND: Demand forecasting is the area of predictive analytics devoted to
predicting future volumes of services or consumables. Fair understanding and
estimation of how demand will vary facilitates the optimal utilization of
resources. In a medical laboratory, accurate forecasting of future demand, that
is, test volumes, can increase efficiency and facilitate long-term laboratory
planning. Importantly, in an era of utilization management initiatives,
accurately predicted volumes compared to the realized test volumes can form a
precise way to evaluate utilization management initiatives. Laboratory test
volumes are often highly amenable to forecasting by time-series models; however,
the statistical software needed to do this is generally either expensive or
highly technical. METHOD: In this paper, we describe an open-source web-based
software tool for time-series forecasting and explain how to use it as a demand
forecasting tool in clinical laboratories to estimate test volumes. RESULTS: This
tool has three different models, that is, Holt-Winters multiplicative, Holt
Winters additive, and simple linear regression. Moreover, these models are ranked
and the best one is highlighted. CONCLUSION: This tool will allow anyone with
historic test volume data to model future demand.
PMID- 28400997
TI - Congenital Uterine Arteriovenous Malformation Presenting as Postcoital bleeding:
A Rare Presentation of a Rare Clinical Condition.
AB - Congenital uterine arteriovenous malformation (AVM) is an extremely rare
condition with <100 cases documented in literature. We report multiparous women
presenting to us with a history of postcoital bleed. Initial Doppler
ultrasonography was consistent with features suggestive of AVM. Subsequently,
computed tomography (CT) angiography confirmed the diagnosis. Embolization was
chosen as the treatment because of the large extension of AVM and the risk of
hemorrhage during hysterectomy. The patient was discharged in a stable condition
with a plan of repeat embolization in the next setting. At 6 and 12 weeks of
follow-up, she did not experience any further episodes of bleed. The purpose of
this case report is to highlight the salient clinical features, diagnosis, and
the management options available for this rare clinical condition.
PMID- 28400998
TI - Apparent Diffusion Coefficient Measurement in Mediastinal Lymphadenopathies:
Differentiation between Benign and Malignant Lesions.
AB - OBJECTIVES: We aimed to prospectively assess the diagnostic value of apparent
diffusion coefficient (ADC) measurement in the differentiation of benign and
malignant mediastinal lymphadenopathies. MATERIALS AND METHODS: The study
included 63 consecutive patients (28 women, 35 men; mean age 59.3 years) with 125
mediastinal lymphadenopathies. Echoplanar diffusion-weighted magnetic resonance
imaging of the mediastinum was performed with b-factors of 0 and 600 mm2/s before
mediastinoscopy and mediastinotomy, and ADC values were measured. The ADC values
were compared with the histological results, and statistical analysis was done. P
< 0.05 was considered statistically significant. RESULTS: The mean ADC value of
malignant mediastinal lymphadenopathy (1.030 +/- 0.245 * 10-3 mm2/s) was
significantly lower (P < 0.05) when compared to benign lymphadenopathies (1.571
+/- 0.559 * 10-3 mm2/s). For differentiating malignant from benign mediastinal
lymphadenopathy, the best result was obtained when an ADC value of 1.334 * 10-3
mm2/s was used as a threshold value; area under the curve 0.848, accuracy 78.4%,
sensitivity 66%, specificity of 86%, positive predictive value 76.7%, and
negative predictive value of 79.2%. Interobserver agreement was excellent for ADC
measurements. CONCLUSIONS: ADC measurements could be considered an important
supportive method in differentiating benign from malignant mediastinal
lymphadenopathies.
PMID- 28401000
TI - MiRNA-27a promotes the proliferation and invasion of human gastric cancer MGC803
cells by targeting SFRP1 via Wnt/beta-catenin signaling pathway.
AB - This study aims to elucidate the effects of microRNA-27a (miR-27a) on the
proliferation and invasion of gastric cancer (GC) cells by targeting SFRP1 via
Wnt/beta-catenin signaling pathway. GC and normal adjacent tissues were collected
from 273 GC patients. Human gastric cancer cell line (MGC803) and normal human
gastric mucosal cell line (GES-1) were cultured. The miR-27a mRNA expression was
analyzed using Quantitative real-time polymerase chain reaction (qRT-PCR).
Immunohistochemistry (IHC) test was used to detect miR-27a and SFRP1 protein
expressions. After transfection, cells were divided into five groups: the
negative control (NC) group, the miR-27a inhibitor group, the miR-27a mimics
group, the miR-27a inhibitor + SFRP1 siRNA group and the miR-27a mimics + SFRP1
overexpression group. Western blotting was conducted to test SFRP1 and Wnt/beta
catenin protein expression. Analysis for the target gene of miR-27a was performed
using Luciferase assay. Cell proliferation, migration and invasion were
determined by CCK8 and Transwell assay. The dual-luciferase reporter assay system
was applied to analyze the effects of miR-27a on Wnt/beta-catenin signaling
pathway. In GC tissue and cell line, miR-27a protein and mRNA expressions were up
regulated, and SFRP1 protein and mRNA expressions were down-regulated. Luciferase
assay indicated that miR-27a might target SFRP1 and regulate its expressions.
When miR-27a was down-regulated, SFRP1 was up-regulated, and beta-catenin, Wnt, p
beta-catenin, and p-Wnt were significantly down-regulated. Compared with the NC
group, the proliferation, migration and invasion of GC cells were remarkably
increased in the miR-27a group, but these were declined in the miR-27a mimics +
SFRP1 overexpression group. The proliferation, migration and invasion of GC cells
were elevated in the miR-27a inhibitor + SFRP1 siRNA group compared with the miR
27a inhibitor group. These results showed that miR-27a was highly expressed in GC
tissues and cells, and it might promote cell proliferation, migration and
invasion by targeting SFRP1 via the activation of Wnt/beta-catenin signaling
pathway.
PMID- 28401001
TI - Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric oxide
mediated ERK/Slug signaling pathway.
AB - Nitric oxide (NO) is an important signaling molecule and a component of the
inflammatory cascade. Besides, it is also involved in tumorigenesis. Aberrant
upregulation and activation of the ERK cascade by NO often leads to tumor cell
development. However, the role of ERK inactivation induced by the negative
regulation of NO during apoptosis is not completely understood. In this study,
treatment of A549 and PC9 human lung adenocarcinoma cell lines with cordycepin
led to a reduction in their viability. Analysis of the effect of cordycepin
treatment on ERK/Slug signaling activity in the A549 cell line revealed that LPS
induced inflammatory microenvironments could stimulate the expression of TNF
alpha, CCL5, IL-1beta, IL-6, IL-8 and upregulate NO, phospho-ERK (p-ERK), and
Slug expression. In addition, constitutive expression of NO was observed.
Cordycepin inhibited LPS-induced stimulation of iNOS, NO, p-ERK, and Slug
expression. L-NAME, an inhibitor of NOS, inhibited p-ERK and Slug expression. It
was also found that cordycepin-mediated inhibition of ERK downregulated Slug,
whereas overexpression of ERK led to an upregulation of Slug levels in the
cordycepin-treated A549 cells. Inhibition of Slug by siRNA induced Bax and
caspase-3, leading to cordycepin-induced apoptosis. Cordycepin-mediated
inhibition of ERK led to a reduction in phospho-GSK3beta (p-GSK3beta) and Slug
levels, whereas LiCl, an inhibitor of GSK3beta, upregulated p-GSK3beta and Slug.
Overall, the results obtained indicate that cordycepin inhibits the ERK/Slug
signaling pathway through the activation of GSK3beta which, in turn, upregulates
Bax, leading to apoptosis of the lung cancer cells.
PMID- 28400999
TI - mTOR function and therapeutic targeting in breast cancer.
AB - The mTOR pathway was discovered in the late 1970s after the compound and natural
inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces
hygroscopicus. mTOR is serine/threonine kinase belonging to the phosphoinositide
3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1
and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy
whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling
is often over active in multiple cancer types including breast cancer. This can
involve mutations in mTOR itself but more commonly, in breast cancer, this is
related to an increase in activity of ErbB family receptors or alterations and
mutations of PI3K signaling. Rapamycin and its analogues (rapalogues) bind to the
intercellular receptor FKBP12, and then predominantly inhibit mTORC1 signaling
via an allosteric mechanism. Research has shown that inhibition of mTOR is a
useful strategy in tackling cancers, with it acting to slow tumor growth and
limit the spread of a cancer. Rapalogues have now made their way into the clinic
with the rapalogue everolimus (RAD-001/Afinitor) approved for use in conjunction
with exemestane, in post-menopausal breast cancer patients with advanced disease
who are HER-2 negative (normal expression), hormone receptor positive and whose
prior treatment with non-steroidal aromatase inhibitors has failed. Testing
across multiple trials has proven that everolimus and other rapalogues are a
viable way of treating certain types of cancer. However, rapalogues have shown
some drawbacks both in research and clinically, with their use often activating
feedback pathways that counter their usefulness. As such, new types of inhibitors
are being explored that work via different mechanisms, including inhibitors that
are ATP competitive with mTOR and which act to perturb signaling from both mTOR
complexes.
PMID- 28401002
TI - Gpr110 deficiency decelerates carcinogen-induced hepatocarcinogenesis via
activation of the IL-6/STAT3 pathway.
AB - Hepatocarcinogenesis is a complex process that includes pronounced
necroinflammation, unregulated hepatocyte damage, subsequent extensive fibrosis,
and carcinogenesis. GPR110 was an adhesion G protein-coupled receptor. Analysis
of the expression pattern of Gpr110 in mice displayed that Gpr110 was expressed
highly in liver, implicating the tissue compartments where Gpr110 could execute
its functions, the role of Gpr110 in the physiological and pathological state of
liver remains unclear. Based on a Gpr110 knockout mouse model, we evaluated the
role of Gpr110 in hepatocarcinogenesis by using a carbon tetrachloride (CCl4)
induced liver injury and fibrosis model, as well as diethylnitrosamine (DEN) plus
CCl4-induced liver cancer model. In this study, we found subdued chronic liver
injury, reduced compensatory proliferation, lower liver fibrosis, but enhanced
inflammation occurred in Gpr110-/- mice during CCl4 challenge. In addition,
Gpr110-/- mice were resistant to liver tumorigenesis induced by DEN plus CCl4
injection. Molecular mechanisms underlying these differences correlated with
augmented activation of the IL-6/STAT3 pathway, which exerted hepatoprotective
effects during liver damage, fibrosis, and oncogenesis in Gpr110-/- mice.
Furthermore, pharmacological inhibition of the activation of the IL-6/STAT3
pathway enhanced hepatic fibrosis and promoted DEN plus CCl4-induced
carcinogenesis in Gpr110-/- mice. In summary, absence of Gpr110 decelerates liver
fibrosis/cirrhosis progressing into tumorigenesis, due to strengthening
activation of the IL-6/STAT3 pathway, leading to a weaker liver injury and
fibrosis microenvironment. It is indicated that targeting Gpr110 and activating
the IL-6/STAT3 pathway may be considered to be preventive methods for some
cirrhosis transition.
PMID- 28401003
TI - Histone demethylase PHF8 promotes progression and metastasis of gastric cancer.
AB - Histone demethylase plant homeodomain (PHD) finger protein 8 (PHF8) has been
implicated in tumor development and malignant progression in various types of
cancers. However, its potential roles in gastric cancer (GC) have not been
explored. In this report, we show that PHF8 expression is upregulated in GC
tissues, and the enhanced PHF8 level indicates a poor prognosis of GC patients.
PHF8 knockdown reduces proliferation and metastasis of GC cells, while PHF8
overexpression has the opposite effects. Mechanistically, PHF8 interacts with
beta-catenin, and binds to the promoter region of vimentin, leading to the
promotion of vimentin transcription. In addition, we show that H. pylori, the
single most important risk factor for GC, markedly induce PHF8 expression. Our
results suggest that H. pylori-induced PHF8-beta-catenin-vimentin axis activation
is a novel mechanism for GC malignant progression. Thus, we identify PHF8 as an
oncogenic factor of GC, and suggest PHF8 might be a potential molecular target
for therapeutic approaches for GC.
PMID- 28401004
TI - UXT-AS1-induced alternative splicing of UXT is associated with tumor progression
in colorectal cancer.
AB - Increasing evidence indicates that long non-coding RNAs (lncRNAs) can act as
crucial regulators of tumor progression. In the present study, UXT-AS1 was found
to be significantly upregulated in colorectal cancer (CRC) and high expression
levels of UXT-AS1 were significantly associated with poor prognosis in CRC
patients. In addition, upregulation of UXT-AS1 resulted in inhibition of cell
apoptosis and the promotion of cell proliferation. Moreover, by regulating the
alternative splicing of UXT, upregulation of UXT-AS1 decreased the UXT1
transcript which promoted cell apoptosis and increased the UXT2 transcript which
promoted cell proliferation. Thus, aberrant high expression of UXT-AS1 can
promote CRC progression by changing the alternative splicing of UXT from the UXT1
transcript to the UXT2 transcript. In conclusion, our findings suggest that the
regulation of CRC progression is by UXT-AS1-induced alternative splicing of UXT,
and the expression level of UXT-AS1 may be a potential prognostic biomarker and
therapy target in CRC patients.
PMID- 28401005
TI - Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in
gastric cancer.
AB - Globally, gastric cancer is the second leading cause of cancer deaths because of
the lack of effective treatments for patients with advanced tumors when curative
surgery is not possible. Thus, there is an urgent need to identify molecular
targets in gastric cancer that can be used for developing novel therapies and
prolonging patient survival. Checkpoint kinase 1 (Chk1) is a crucial regulator of
cell cycle transition in DNA damage response (DDR). In our study, we report that
Chk1 plays an important role in promoting gastric cancer cell survival and
growth, which serves as an effective therapeutic target in gastric cancer. First,
Chk1 ablation by small interfering RNA could significantly inhibit cell
proliferation and sensitize the effects of ionizing radiation (IR) treatment in
both p53 wild type gastric cancer cell line AGS, and p53 mutant cell line MKN1.
Secondly, we tested the anticancer effects of Chk1 chemical inhibitor LY2606368,
which is a novel Chk1/2 targeted drug undergoing clinical trials in many
malignant diseases. We found that LY2606368 can induce DNA damage, and remarkably
suppress cancer proliferation and induce apoptosis in AGS and MKN1 cells.
Moreover, we identified that LY2606368 can significantly inhibit homologous
recombination (HR) mediated DNA repair and thus showed marked synergistic
anticancer effect in combination with poly (ADP-ribose) polymerase 1 (PARP1)
inhibitor BMN673 in both in vitro studies and in vivo experiments using a gastric
cancer PDx model. The synergy between LY2606368 and PARP1 was likely caused by
impaired the G2M checkpoint due to LY2606368 treatment, which forced mitotic
entry and cell death in the presence of BMN673. In conclusion, we propose that
Chk1 is a valued target for gastric cancer treatment, especially Chk1 inhibitor
combined with PARP inhibitor may be a more effective therapeutic strategy in
gastric cancer.
PMID- 28401007
TI - Nodal signaling activates the Smad2/3 pathway to regulate stem cell-like
properties in breast cancer cells.
AB - Nodal signaling plays several vital roles in the embryogenesis process. However,
its reexpression in breast cancer is correlated with cancer progression,
metastasis and poor prognosis. Recently, Nodal has also been reported to regulate
self-renewal capacity in pancreatic cancer. This study aimed to explore the role
of Nodal in breast cancer stem cells (BCSCs) and the underlying mechanisms.
Therefore, the immunohistochemistry staining of Nodal in 135 human breast cancer
cases was performed to analyzed the relationship of Nodal signaling, clinical
outcomes and BCSC marker. And the results showed that high Nodal expression was
positively correlated with poor prognosis and BCSC marker expression in breast
cancer samples. We further assessed the effects of Nodal in regulating the BCSC
properties in breast cancer cell lines and xenografts. Then, SB431542 was
administered in vitro and in vivo to explore the function of the Smad2/3 pathway.
And we demonstrated that Nodal signaling up-regulated the expression of ALDH1,
CD44, CD133, Sox2, Oct4 and Nanog by activating the Smad2/3 pathway, thereby
enhancing the tumorigenicity and sphere-forming ability of breast cancer cells.
Furthermore, treatment with SB431542 could inhibit the properties of BCSCs in
vitro and in vivo. In conclusion, these findings indicate that Nodal signaling
may play a vital role in maintaining the BCSC phenotype in breast cancer and
serve as a potential target to explore BCSC-specific therapies.
PMID- 28401006
TI - Genomic and proteomic characterization of ARID1A chromatin remodeller in
ampullary tumors.
AB - AT rich interactive domain 1A (ARID1A) is one of the most commonly mutated genes
in a broad variety of tumors. The mechanisms that involve ARID1A in ampullary
cancer progression remains elusive. Here, we evaluated the frequency of ARID1A
and KRAS mutations in ampullary adenomas and adenocarcinomas and in duodenal
adenocarcinomas from two cohorts of patients from Singapore and Romania,
correlated with clinical and pathological tumor features, and assessed the
functional role of ARID1A. In the ampullary adenocarcinomas, the frequency of
KRAS and ARID1A mutations was 34.7% and 8.2% respectively, with a loss or
reduction of ARID1A protein in 17.2% of the cases. ARID1A mutational status was
significantly correlated with ARID1A protein expression level (P=0.023). There
was a significant difference in frequency of ARID1A mutation between Romania and
Singapore (2.7% versus 25%, P=0.04), suggestive of different etiologies. One
somatic mutation was detected in the ampullary adenoma group. In vitro studies
indicated the tumor suppressive role of ARID1A. Our results warrant further
investigation of this chromatin remodeller as a potential early biomarker of the
disease, as well as identification of therapeutic targets in ARID1A mutated
ampullary cancers.
PMID- 28401008
TI - Autophagy inhibits cell death induced by the anti-cancer drug morusin.
AB - Autophagy is a cellular process by which damaged organelles and dysfunctional
proteins are degraded. Morusin is an anti-cancer drug isolated from the root bark
of Morus alba. Morusin induces apoptosis in human prostate cancer cells by
reducing STAT3 activity. In this study, we examined whether morusin induces
autophagy and also examined the effects of autophagy on the morusin-induced
apoptosis. Morusin induces LC3-II accumulation and ULK1 activation in HeLa cells.
In addition, we found that induction of ULK1 Ser317 phosphorylation and reduction
of ULK1 Ser757 phosphorylation occurred simultaneously during morusin-induced
autophagy. Consistently, morusin induces autophagy by activation of AMPK and
inhibition of mTOR activity. Next, we investigated the role of autophagy in
morusin-induced apoptosis. Inhibition of autophagy by treating cells with the 3
methyladenine (3-MA) autophagic inhibitor induces high levels of morusin-mediated
apoptosis, while treatment of cells with morusin alone induces moderate levels of
apoptosis. Cell survival was greatly reduced when cells were treated with morusin
and 3-MA. Taken together, morusin induces autophagy, which is an impediment for
morusin-induced apoptosis, suggesting combined treatment of morusin with an
autophagic inhibitor would increase the efficacy of morusin as an anti-cancer
drug.
PMID- 28401009
TI - Integrin beta1 is a critical effector in promoting metastasis and chemo
resistance of esophageal squamous cell carcinoma.
AB - Metastasis of esophageal squamous cell carcinoma (ESCC) remains a challenge in
clinical practice. In this study, we clarified that integrin beta1 (ITGB1) plays
critical roles in the metastasis of ESCC. By analyzing the expression of integrin
beta1 in ESCC specimens, we found that the expression of this integrin was higher
in malignant than in normal tissues and that this increase was associated with
lymph node metastasis. Moreover, in vitro functional experiments demonstrated
that deletion of integrin beta1 impaired the motility of ESCC cells, and we also
showed that integrin beta1 deletion significantly inhibited metastases formation
in the lungs and lymph nodes of two murine models. Mechanistically, integrin
beta1 promoted cellular motility by regulating the FAK-Rac1 signaling pathway.
Finally, we found that blocking integrin beta1 significantly impaired the
resistance of ESCC cells to cisplatin (DDP) treatment based on in vitro and in
vivo experiments. Overall, our data suggest that integrin beta1 promotes
metastasis and confers DDP resistance to ESCC, which provides experimental
evidence for targeting this protein to treat ESCC in the future.
PMID- 28401010
TI - Downregulation of ACSM3 promotes metastasis and predicts poor prognosis in
hepatocellular carcinoma.
AB - Understanding mechanisms of cancer metastasis is crucial for reduction of cancer
mortality. Acyl-CoA medium-chain synthetase 3 (ACSM3) is an acyl-CoA synthetase
which takes part in the first step of fatty acid metabolism. However, the
expression, clinical significance and biological function of ACSM3 remain unknown
in hepatocellular carcinoma (HCC). In this study, the expression and prognostic
relevance of ACSM3 were investigated by tissue microarray and HCC clinical
samples. Migration and invasion assays were carried out for functional analysis
in vitro and a xenograft model was used to analyze the effects of ACSM3 on cancer
metastasis in vivo. Furthermore, human phospho-kinase array assays were performed
to explore molecular mechanisms of ACSM3 in HCC. The results showed ACSM3 was
downregulated in HCC tissues. HCC patients with low expression of ACSM3 exhibited
poor prognosis. Overexpression of ACSM3 attenuated migration and invasion of HCC
cells in vitro and in vivo and downregulated the phosphorylation of WNK1 and AKT.
Our findings indicate ACSM3 is a novel prognostic marker and a potential
therapeutic target for HCC.
PMID- 28401011
TI - NVM-1 predicts prognosis and contributes to growth and metastasis in
hepatocellular carcinoma.
AB - Novel metastasis-promoting gene 1 (NVM-1) has a significantly elevated protein
level in a variety of tumor tissues and is involved in metastasis. However, its
functions in hepatocellular carcinoma (HCC) are not clear. The current study
aimed to investigate the functions of NVM-1 in cell proliferation, apoptosis, and
epithelial-mesenchymal transition in HCC. NVM-1 protein expression in HCC was
assessed by immunohistochemical staining. In vitro, cell proliferation,
apoptosis, and aggressiveness were determined by CCK-8, fluorescence-assisted
cell sorting, TdT-UTP nick-end labeling, and transwell assays, respectively. For
in vivo studies, NVM-1 knockdown HCC cells were transplanted into BALB/c nude
mice. NVM-1 was frequently upregulated in HCC tissues and positive NVM-1
expression was linked with poor prognosis. NVM-1 depletion significantly
inhibited cell proliferation, migration, and invasion abilities in vitro and in
vivo. Apoptosis was induced after NVM-1 knockdown. In conclusion, positive NVM-1
expression confers poor prognosis to HCC patients and the NVM-1 protein level
correlates with HCC cell proliferation, apoptosis, and EMT.
PMID- 28401012
TI - NRSN2 promotes osteosarcoma cell proliferation and growth through PI3K/Akt/MTOR
and Wnt/beta-catenin signaling.
AB - Osteosarcoma is the most common bone cancer in children and adults. However, its
pathogenesis, especially molecular mechanisms remain elusive. In current study,
we screened GEO Database and found a poorly studied protein Neurensin-2 (NRSN2),
which is highly expressed in osteosarcoma tissues. Neurensin-2 (NRSN2) is a small
neuronal membrane protein and localized in small vesicles in neural cells,
previous study found that it has been implicated in hepatocellular carcinoma
(HCC) and non-small cell lung cancer (NSCLC). We here report that the expression
of NRSN2 is more commonlyelevated in 18 fresh osteosarcoma tissues. Furthermore,
both loss- and gain-functions assays revealed that NRSN2 could promote
osteosarcoma cell proliferation and growth both in vitro and in vivo. In
addition, we further found that those effects on osteosarcoma by NRSN2 are
associated with the dysregulated PI3K/AKT/mTOR signaling and Wnt/beta-catenin
signaling. In conclusion, our study found a novel oncogenic protein, NRSN2, which
promotes osteosarcoma cell proliferation and as a membrane protein, NRSN2 also
could be a potential treatment target for osteosarcoma.
PMID- 28401013
TI - Resistin confers resistance to doxorubicin-induced apoptosis in human breast
cancer cells through autophagy induction.
AB - Clear evidence has linked obesity to a high risk of incidence as well as poor
clinical outcome of breast cancer. It has been proven that changes in the levels
of adipokines caused by obesity are associated with the initiation and
progression of breast cancer. Resistin is a novel adipokine that is upregulated
in breast cancer patients and promotes breast cancer cell growth, invasion, and
migration. The aim of the study was to investigate whether resistin affected the
efficacy of doxorubicin (Dox), one of the most effective anthracycline
chemotherapeutic agents in the treatment of breast cancer. Treatment with
resistin significantly attenuated Dox-induced apoptosis in a dose- and time
dependent manner, resulting in an increase in breast cancer cells survival.
Moreover, resistin significantly induced autophagy flux and inhibition of
autophagy abrogated the pro-survival effect of resistin in doxorubicin-treated
cells. Furthermore, the AMPK/mTOR/ULK1 and JNK signaling pathways were activated
by resistin treatment. Inhibition of these two pathways markedly reduced the
ratio of LC3B-II/LC3B-I and increased cell apoptosis induced by Dox. For the
first time, our findings indicate that resistin confers resistance to doxorubicin
induced apoptosis through autophagy induction and that this process involves the
activation of AMPK/mTOR/ULK1 and JNK signaling pathways. Our findings suggest
that resistin antagonism may be a novel strategy to overcome resistance to
doxorubicin-based chemotherapy in breast cancer patients.
PMID- 28401014
TI - Cyproheptadine use in hepatocellular carcinoma.
AB - This study was conducted to compare the effectiveness of Cyproheptadine (CY) use
in patients with different stages of HCC who received different therapeutic
modalities; such a comparison has not been conducted by previous large,
prospective, randomized studies. We conducted a cohort study using the Taiwan
Cancer Registry Database for analysis. We included patients diagnosed as having
HCC from January 1, 2002, to December 31, 2011. The patient cohort comprised
those who received different treatments, and we compared patients who received CY
with those who did not. In total, 70,885 patients were included, and the mean
follow-up duration was 1.95 years. The adjusted hazard ratio (aHR) of all-cause
deaths significantly decreased in all stages in the patients who received
palliative treatments with CY use compared with those who received palliative
treatments without CY use (all P < 0.0001 and aHR = 0.76, 0.80, 0.66, and 0.66
for stages I, II, III, and IV, respectively). Among the patients who received no
treatment, CY use alone reduced the risk of all-cause deaths in stages I-IV (all
P < 0.0001 and aHR = 0.61, 0.57, 0.54, and 0.52 for stages I, II, III, and IV,
respectively). Among the patients with clinical stage I-II HCC (as determined by
the American Joint Committee on Cancer) who received curative treatments, CY use
did not reduce all-cause deaths. CY use might improve survival in patients with
HCC receiving palliative treatments or no treatment regardless of clinical
stages.
PMID- 28401015
TI - Study of natural IgG antibodies against vascular endothelial growth factor
receptor 1 in hepatocellular carcinoma.
AB - Natural antibodies have been found to have anti-tumorigenic function. This study
was designed to investigate whether natural IgG antibodies against vascular
endothelial growth factor receptor 1 (VEGFR1) could suppress the growth of
hepatocellular carcinoma (HCC) cells. Three HCC cell lines and A549 lung cancer
cells were used for this study. They were grown, respectively, with human plasma
positive or negative for anti-VEGFR1 IgG. Cell viability, apoptosis and VEGFR1
gene expression were examined. Three patients with HCC were recruited for a case
study. The results showed that plasma anti-VEGFR1 IgG significantly inhibited the
proliferation of all three HCC cell lines but not A549 cell line; the proportions
of apoptotic cells were significantly higher in HCC cells treated with anti
VEGFR1 IgG positive plasma than those treated with IgG negative plasma. The
expression of the VEGFR1 gene was significantly higher in HCC cells than A549
cells. Of three HCC patients who received transfusion of anti-VEGFR1 IgG positive
plasma, two cases with stage B showed a good response to the treatment but one
with distant metastasis did not. Human plasma IgG against VEGFR1 may be a
promising agent for anti-HCC therapy.
PMID- 28401016
TI - Data mining and medical world: breast cancers' diagnosis, treatment, prognosis
and challenges.
AB - The amount of data in electronic and real world is constantly on the rise.
Therefore, extracting useful knowledge from the total available data is very
important and time consuming task. Data mining has various techniques for
extracting valuable information or knowledge from data. These techniques are
applicable for all data that are collected inall fields of science. Several
research investigations are published about applications of data mining in
various fields of sciences such as defense, banking, insurances, education,
telecommunications, medicine and etc. This investigation attempts to provide a
comprehensive survey about applications of data mining techniques in breast
cancer diagnosis, treatment & prognosis till now. Further, the main challenges in
these area is presented in this investigation. Since several research studies
currently are going on in this issues, therefore, it is necessary to have a
complete survey about all researches which are completed up to now, along with
the results of those studies and important challenges which are currently exist
in this area for helping young researchers and presenting to them the main
problems that are still exist in this area.
PMID- 28401017
TI - miR-495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal
transition via Etk/BMX.
AB - miR-495 serves as an oncogenic miRNA or a tumor suppressor in different types of
cancer. However, its role in the drug resistance of small cell lung cancer (SCLC)
remains unidentified. In this study, we investigated whether miR-495 regulates
the chemoresistance of SCLC through the epithelial-mesenchymal transition (EMT)
via Epithelial and endothelial tyrosine kinase (Etk/BMX) using two drug-resistant
cell lines. Loss- and gain-of-function experiments showed miR-495 regulated cell
proliferation, tumor growth and drug resistance. miR-495 suppression or Etk/BMX
elevation in SCLC specimens was correlated with poor pathologic stage and
survival time. Etk/BMX was one of the directly targeted genes of miR-495. Ectopic
expression of Etk/BMX obviously rescued the miR-495 elevation elevation-induced
inhibition of drug resistance. Etk/BMX over-expression led to higher levels of
EMT mesenchymal factors (Zeb-2, Twist, Vim) and lower levels of the epithelial
molecule beta-catenin, while suppression of Etk/BMX showed the opposite trend.
Knockdown of Zeb-2 and Twist inhibited the chemoresistance of cells. Our study
revealed that miR-495 promoted the chemoresistance of SCLC through the epithelial
mesenchymal transition via Etk/BMX. miR-495 re-expression or Etk/BMX depletion is
a promising strategy for interfering with chemoresistance in SCLC.
PMID- 28401018
TI - OTX2 expression contributes to proliferation and progression in Myc-amplified
medulloblastoma.
AB - Medulloblastoma is one of the most prevalent pediatric brain malignancies,
accounting for approximately 20% of all primary CNS tumors in children under the
age of 19. OTX2 is the member of a highly conserved family of bicoid-like
homeodomain transcription factors responsible for the regulation of cerebellar
development and of current investigational interest in the tumorigenesis of
medulloblastoma. Recent studies have revealed that Group 3 and Group 4
medulloblastomas show marked overexpression of OTX2 with a concurrent
amplification of the MYC and MYCN oncogenes, respectively, correlating with
anaplasticity and unfavorable patient outcomes. More recent attempts at
elucidating the mechanism of OTX2-driven oncogenesis at the cellular level has
also revealed that OTX2 may confer stem-cell like properties to tumor cells via
epigenetic regulation. The review seeks to define the interaction pathways and
binding partners involved in OTX2 function, its usefulness as a molecular marker
for risk stratification and prognosis, and the mechanism by which it drives tumor
maintenance. Additionally, it will preview unpublished data by our group
highlighting the unanticipated involvement of OTX2 in the control of cellular
metabolism.
PMID- 28401019
TI - A tumor vessel-targeting fusion protein elicits a chemotherapeutic bystander
effect in pancreatic ductal adenocarcinoma.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease characterized
by a prominent desmoplastic stroma that may constrain tumor progression but also
limit the access of therapeutic drugs. In this study, we explored a tumor
targeting strategy that enlists an engineered anti-angiogenic protein consisting
of endostatin and cytosine deaminase linked to uracil phosphoribosyltransferase
(EndoCD). This protein selectively binds to tumor vessels to compromise tumor
angiogenesis and converts the non-toxic 5-fluorocytosine (5-FC) to the cytotoxic
5-fluorouracil to produce a chemotherapeutic bystander effect at the pancreatic
tumor site. We found that resveratrol increased the protein stability of EndoCD
through suppression of chymotrypsin-like proteinase activity and synergistically
enhances EndoCD-mediated 5-FC-induced cell killing. In various PDAC mouse models,
the EndoCD/5-FC/resveratrol regimen decreased intratumoral vascular density and
stroma formation and enhances apoptosis in tumors cells as well as in surrounding
endothelial, pancreatic stellate, and immune cells, leading to reduced tumor
growth and extended survival. Thus, the EndoCD/5-FC/resveratrol combination may
be an effective treatment option for PDAC.
PMID- 28401021
TI - Integrated mRNA and lncRNA expression profiling for exploring metastatic
biomarkers of human intrahepatic cholangiocarcinoma.
AB - Long noncoding RNAs (lncRNAs) is crucial for various human cancers, but the
function and mechanism of lncRNAs is largely unknown in human intrahepatic
cholangiocarcinoma (ICC), the second most common liver cancer. In this study, we
performed transcriptomic profiling of ICC and normal tissues, and found 2148
lncRNAs and 474 mRNAs were significantly upregulated, whereas 568 lncRNAs and 409
mRNAs were downregulated in ICC tissues. Enrichment analysis suggests these
differentially expressed genes mainly focus on response to stimulus, development,
and cell proliferation. Further, potential lncRNAs involved in five signaling
pathways (ERBB, JAK/STAT, MAPK, VEGF and WNT) were constructed by highly co
expressed with mRNAs in these signaling pathways. The differentially expressed
lncRNA-mRNA co-regulated signaling pathways in ICC were further confirmed by
lncRNA target prediction. Finally, the differentially expressed lncRNAs were
confirmed by quantitative real-time PCR in 32 paired ICC and adjacent tissues.
The correlation analysis between the expression levels of lncRNAs and
clinicopathologic characteristics showed that EMP1-008, ATF3-008, and RCOR3-013
were observed significantly downregulated in ICC with tumor metastasis. These
findings suggested that lncRNA expression profiling in ICC is profoundly
different from that in noncancerous tissues, and lncRNA may be used as a
potential diagnostic and prognostic biomarker for ICC metastasis.
PMID- 28401020
TI - Control of tissue size and development by a regulatory element in the yorkie
3'UTR.
AB - Regulation of the Hippo pathway via phosphorylation of Yorkie (Yki), the
Drosophila homolog of human Yes-associated protein 1, is conserved from
Drosophila to humans. Overexpression of a non-phosphorylatable form of Yki
induces severe overgrowth in adult fly eyes. Here, we show that yki mRNA
associates with microsomal fractions and forms foci that partially colocalize to
processing bodies in the vicinity of endoplasmic reticulum. This localization is
dependent on a stem-loop (SL) structure in the 3' untranslated region of yki.
Surprisingly, expression of SL deleted yki in eye imaginal discs also results in
severe overgrowth phenotypes. When the structure of the SL is disrupted, Yki
protein levels increase without a significant effect on RNA levels. When the SL
is completely removed, protein levels drastically increase, but in this case, due
to increased RNA stability. In the latter case, we show that the increased RNA
accumulation is due to removal of a putative miR-8 seed sequence in the SL. These
data demonstrate the function of two novel regulatory mechanisms, both controlled
by the yki SL element, that are essential for proper Hippo pathway mediated
growth regulation.
PMID- 28401022
TI - The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous
cell carcinoma.
AB - Isocitrate dehydrogenase 2 (IDH2) is the rate-limiting enzyme in the
tricarboxylic acid (TCA) cycle in cellular metabolism. Growing evidence indicates
that IDH2 plays a crucial role in the development of cancer. We aimed to
investigate the expression level of IDH2 and its prognostic value in esophageal
squamous cell cancer (ESCC). We evaluate the IDH2 expression and prognostic value
in ESCC by immunohistochemical (IHC) staining, quantitative real-time polymerase
chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK8),
clonogenic and invasion assays were performed to verify the IDH2 function in
vitro. The protein expression level of IDH2 was significantly upregulated in ESCC
tissues (IHC, Western blotting, all P<0.001) despite no significant difference at
mRNA expression level (P>0.05). Kaplan-Meier analysis showed that IDH2
overexpression in ESCC patients was significantly related to worse overall
survival (OS) and progression-free survival (PFS), P = 0.003 and 0.002,
respectively. The univariate and multivariate analyses revealed that IDH2
overexpression served as an independent prognostic factor for OS and PFS (all
P<0.005) in ESCC. The OD450 value, colony formation and invasive cell number were
decreased in the shIDH2 groups (all P<0.0001). The upregulation of IDH2 in ESCC
cells showed opposite effects (all P<0.05). Additionally, IDH2 knockdown
phenotype can be rescued by shRNA-resistant IDH2 (all P<0.05). These results
demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable
prognostic marker for ESCC patients.
PMID- 28401023
TI - Biopolymer based nanosystem for doxorubicin targeted delivery.
AB - This study describes formation of an actively and passively targeted, water
soluble drug delivery system (DDS) which contains doxorubicin (DOX). The system
comprises two biocompatible and biodegradable polymers: poly-gamma-glutamic acid
(PGA) and chitosan (CH). Self-assembly of these biopolymers in aqueous medium
results stable nanoparticles (NPs) with a hydrodynamic size of 80-150 nm and
slightly negative surface charge. Folic acid (FA) was used as targeting agent
bonded to the polyanion (PA) and also to the surface of the NPs. The NP's
physical stability, active targeting effect, cellular toxicity, release profile
and in vivo anti-tumor efficacy were investigated. It was found that the
targeted, self-assembled nanoparticles are stable at 4 degrees C for several
months, cause better in vitro toxicity effect on folate receptor (FR) positive
cell lines than the doxorubicin or the non-targeted nanosystem and based on its
release profile it is expected, that the nanosystem will remain stable during the
circulation in the body. Pharmacodynamic studies demonstrated that the DOX-loaded
nanoparticles can deliver greater tumor growth inhibition than the free drug
molecules and the liposomal compound, with less general toxicity. It was observed
that the overall survival is the main benefit of the biopolymer based drug
delivery system.
PMID- 28401024
TI - Inhibition of STAT3 signaling blocks obesity-induced mammary hyperplasia in a
mouse model.
AB - Compelling epidemiologic evidence indicates that obesity is a risk factor for
human cancers, including breast. However, molecular mechanisms by which obesity
could contribute to the development of breast cancer remain unclear. To
understand the impact of obesity on breast cancer development, we used a mutant
mouse that expresses a mutated thyroid hormone receptor beta (denoted as PV) with
haplodeficiency of the Pten gene (ThrbPV/PVPten+/- mice). We previously showed
that adult nulliparous female ThrbPV/PVPten+/- mice developed extensive mammary
hyperplasia and breast tumors. In this study, we induced obesity in
ThrbPV/PVPten+/- mice by feeding them a high fat diet (HFD). We found HFD
exacerbated the extent of mammary hyperplasia in ThrbPV/PVPten+/- mice. HFD
elevated serum leptin levels but had no effect on the levels of serum thyroid
stimulating hormone, thyroid hormones, and estrogens. Molecular analysis showed
that the obesity-induced hyperplasia was mediated by the leptin/leptin receptor
JAK1-STAT3 pathway to increase key cell cycle regulators to stimulate mammary
epithelial cell proliferation. Activated STAT3 signaling led to altered
expression in the key regulators of epithelial-mesenchymal-transition (EMT) to
augment invasiveness and migration of mammary proliferating epithelial cells.
Moreover, treatment of HFD-ThrbPV/PVPten+/- mice with a STAT3 inhibitor, S3I-201,
markedly reversed the obesity-induced mammary hyperplasia and reduced EMT signals
to lessen cell invasiveness and migration. Our studies not only elucidated how
obesity could contribute to mammary hyperplasia at the molecular level, but also,
importantly, demonstrated that inhibition of the STAT3 activity could be a novel
treatment strategy for obesity-induced breast cancer progression.
PMID- 28401025
TI - Adult acute precursor B-cell lymphoblastic leukemia presenting as hypercalcemia
and osteolytic bone lesions.
AB - BACKGROUND: Osteolytic bone lesions and hypercalcemia without peripheral blasts B
cell acute lymphoblastic leukemia (B-ALL) is reported in children but rarely seen
in adults. CASE PRESENTATION: We describe the case of a 34-year old man
presenting with hypercalcemia and symptomatic osteolytic bone lesions of
vertebrae and ribs who was initially suspected as having a solid malignancy.
Diagnostic work-up including peripheral blood examination, radiographic and
nuclear studies could, however, not detect a primary tumor. Because of a mild
thrombocytopenia and the lack of a primary focus, a bone marrow biopsy was
performed leading to the diagnosis of Philadelphia chromosome positive precursor
B-ALL. After correction of the hypercalcemia with intravenous fluid
administration, corticoids and bisphosphonates, the patient was treated according
to the HOVON 100 protocol achieving complete molecular remission after the first
cycle of induction chemotherapy. CONCLUSION: Hypercalcemia and osteolytic bone
lesions are rare complications of adult B-ALL and can occur in the absence of
peripheral blastosis. With this case report we would like to emphasize the
importance of clinical awareness. Immediate treatment of hypercalcemia and
initiation of antileukemic treatment is mandatory as a delay of diagnosis might
pose a real and possible life-threatening risk in these patients.
PMID- 28401026
TI - High Dose Gamma Radiation Selectively Reduces GABAA-slow Inhibition.
AB - Studies on the effects of gamma radiation on brain tissue have produced markedly
differing results, ranging from little effect to major pathology, following
irradiation. The present study used control-matched animals to compare effects on
a well characterized brain region following gamma irradiation. Male Sprague
Dawley rats were exposed to 60 Gy of whole brain gamma radiation and, after 24
hours, 48-hours, and one-week periods, hippocampal brain slices were isolated and
measured for anatomical and physiological differences. There were no major
changes observed in tissue appearance or evoked synaptic responses at any post
irradiation time point. However, exposure to 60 Gy of irradiation resulted in a
small, but statistically significant (14% change; ANOVA p < 0.005; n = 9)
reduction in synaptic inhibition seen at 100 ms, indicating a selective
depression of the gamma-aminobutyric acid (GABAA) slow form of inhibition.
Population spike (PS) amplitudes also transiently declined by ~ 10% (p < 0.005; n
= 9) when comparing the 24-hour group to sham group. Effects on PS amplitude
recovered to baseline 48 hour and one week later. There were no obvious negative
pathological effects; however, a subtle depression in circuit level inhibition
was observed and provides evidence for 'radiomodulation' of brain circuits.
PMID- 28401027
TI - Beneficial Effects of Childhood Selective Dorsal Rhizotomy in Adulthood.
AB - BACKGROUND: Selective dorsal rhizotomy (SDR) has been used to treat children
with spastic cerebral palsy (CP) for over three decades. However, little is known
about the outcomes of childhood SDR in adults. Objectives: 1) To study the
effects of childhood SDR on the quality of life and ambulatory function in adult
life. 2) To determine late side effects of SDR in adults. Methods: Adults (>
17.9 years) who underwent SDR in childhood (2 - 17.9 years) between 1987 and 2013
were surveyed in 2015. Patients completed a survey, including questions on
demographic information, quality of life, health, surgical outcomes, motor
function, manual ability, pain, braces/orthotics, post-SDR treatment, living
situation, education level, work status, and side effects of SDR. Results: In
our study population of 294 patients (18.0 - 37.4 years), patients received SDR
during the ages of 2.0 - 17.9 years and were followed up 2.2 to 28.3 years after
surgery. Eighty-four percent had spastic diplegia, 12% had spastic quadriplegia,
and 4% had spastic triplegia. The majority (88%) of patients reported improved
post-SDR quality of life and 1% considered the surgery detrimental. Most (83%)
would recommend the procedure to others and 3% would not. However, patients who
would not recommend SDR to others ambulated with a walker or were not ambulatory
at all prior to SDR. The majority (83%) of patients improved (30%) or remained
stable (53%) in ambulation. Twenty-nine percent of patients reported pain, mostly
in the back and lower limbs, with a mean pain level of 4.4 +/- 2.4 on the Numeric
Pain Rating Scale (NPRS). Decreased sensation in small areas of the lower limbs
was reported by 8% of patients, though this did not affect daily life. Scoliosis
was diagnosed in 28%, with 40% of these patients pursuing treatment. Whether
scoliosis was related to SDR is not clear, though scoliosis is known to occur in
patients with CP and also in the general population. Only 4% of patients
underwent spinal fusion. Orthopedic surgeries were pursued by 59% of patients.
The most common orthopedic surgeries were hamstring lengthenings (31%), Achilles
tendon lengthenings (18%), adductor lengthenings (16%), and derotational
osteotomies (16%). Twenty-four percent of all patients later underwent hip
surgery and 8% had surgeries on their knees. Conclusion: Results of this study
indicate that the beneficial effects of childhood SDR extend to adulthood quality
of life and ambulatory function without late side effects of surgery.
PMID- 28401028
TI - Coexistence of Right Nonrecurrent Nerve and Bifurcated Recurrent Laryngeal Nerve
Pointed by Zuckerkandl's Tubercle.
AB - The recurrent laryngeal nerve (RLN) has many anatomical variations and various
relations with adjacent structures. Identification and total exposure of the
cervical part of the RLN was performed during operations on the thyroid gland. An
extremely rare anatomical variation of the nerve was encountered during the
surgical procedure. Coexistence of both right RLN and non-RLN was observed in one
patient surgically treated with total thyroidectomy. We first exposed the right
RLN with an extralaryngeal terminal bifurcation at its usual position.
Thereafter, we also identified an ipsilateral non-RLN joining the anterior branch
of the RLN just before laryngeal entry. A Zuckerkandl's tubercle has pointed out
the junction of the two nerves. In this period, the incidence of coexistence of
non-RLN and RLN was 0.2% in our series. A non-recurrent course is a rare
anatomical variation of the inferior laryngeal nerve. The coexistence of both non
RLN and RLN is an extremely rare anatomical finding which should be taken into
account during thyroid surgery.
PMID- 28401029
TI - Iatrogenic central retinal artery occlusion after carotid body tumor embolization
and excision.
AB - Objective: To report a case of iatrogenic central retinal artery occlusion after
embolization and surgical resection of carotid body paraganglioma. Methods: Case
report Results: One adult female patient presented with persistent unilateral
visual loss after embolization with Embosphere(r) and Contour(r) microparticles
of carotid body tumor. Fluorescein angiography revealed intraluminal microspheres
in the central retinal artery ramifications. OCT revealed intraretinal spherical,
hyporeflective particles with posterior shadowing. Conclusions: Central retinal
artery occlusion should be assessed as a possible complication after surgical
repair of head and neck paragangliomas.
PMID- 28401030
TI - Macular ischemia after intravitreal amikacin on patient with intraocular foreign
body.
AB - Background: Although still used in third world countries, amikacin has a harmful
effect to be used intravitreally. Purpose: To report macular ischemia after an
intravitreal injection of amikacin Methods: A case report regarding a traumatized
eye of a 26-year-old man that was injected intravitreally with amikacin due to
intraocular foreign body endophthalmitis Results: Angiography and OCT show
macular ischemia due to amikacin toxicity. Conclusion: The case reported here is
to alert about the potential harmful effect of intravitreally injected amikacin
despite its role as an accepted regimen for endohthalmitis cases.
PMID- 28401031
TI - Sella turcica measurements on lateral cephalograms of patients with
neurofibromatosis type 1.
AB - The aim of this study was to measure line segments and areas of sella turcica on
lateral cephalograms with respect to the clinical diagnosis of facial phenotype
of patients with neurofibromatosis type 1 (NF1). Special attention was given to
correlate the measured values with certain tumour types that are typical for this
disease. Material and methods: Lateral cephalograms of 194 individuals were
investigated. Patients with NF1 were further divided according to the detection
and topography of facial plexiform neurofibromas (PNF) taking into account the
distribution pattern of the trigeminal nerve. All patients with PNF showed
unilateral tumour localisation. Patients without any facial PNF constituted a
separate group. Healthy volunteers with ideal occlusion and no history of any
intervention in the maxillofacial region served as a control group. The following
items were determined on the radiographs: sella entrance, sella width, sella
depths, sella diagonal, and sella area. Results: Patients with PNF of the first
and second trigeminal nerve branch or affected in all branches showed highly
statistically significant enlarged sella tucica measurement values. On the other
hand, patients with PNF restricted to one branch only or simultaneously in the
second and third branches showed measurement values that were not different to
those obtained in NF1 patients devoid of facial PNF. The latter group also showed
no difference of sella turcica parameters obtained in the control group.
Conclusion: This study provides evidence for the association of a certain NF1
phenotype with distinct skeletal alterations of the skull base, shown here using
the example of the representation of the sella turcica in the lateral radiograph.
These findings are also relevant in the discussion of NF1 as a disease of bones
and in the assessment of brain development in NF1. Both items are discussed in
relationship to a facial plexiform neurofibroma. Furthermore, the knowledge of
this association of findings provides the clinician with relevant information in
the planning of skull base procedures in these patients.
PMID- 28401032
TI - Modern trends in lipomodeling.
AB - Lipomodeling is the process of relocating autologous fat to change the shape,
volume, consistency, and profile of tissues, with the aim of reconstructing,
rejuvenating, and regenerating body features. There have been several important
advancements in lipomodeling procedures during the last thirty years. Four
clinical steps are important for the success of engraftment: fat harvesting, fat
processing, fat reinjection, and preconditioning of the recipient site. With the
discovery of adipose derived stem cells and dedifferentiated cells, fat cells
become a major tool of regenerative medicine. This article reviews recent trends
in lipomodeling trying to understand most of the issues in this field.
PMID- 28401033
TI - Familial and Contextual Influences on Children's Prosocial Behavior: South
African Caregivers as Adult Protective Shields in Enhancing Child Mental Health.
AB - BACKGROUND: The mental health of children is too frequently overlooked in
resource scarce low and middle-income countries. South Africa represents one of
many country contexts struggling to meet the mental health needs of large numbers
of young people. Family caregivers have been identified as potential protective
influences on child mental health, even for those children being reared with high
exposure to poverty. METHODS: This paper explores contextual influences on South
African caregiver's social-emotional health living in communities impacted by
poverty and food insecurity as they attempt to support their children's prosocial
skills and behavior. Structural Equation Modeling (SEM) was employed to explore
the relationship between neighborhood social cohesion and caregiver report of
child's prosocial behavior as mediated by the caregiver's mental health (n=478).
RESULTS: Results indicated that the more caregivers experience their communities
as socially cohesive, the better their social-emotional well-being, thus
positively related to their reports of children's prosocial behavior.
Furthermore, when there is a male head of household, caregivers reported better
social-emotional well-being in comparison to female headed of household. The more
food secure caregivers also were likely to report better general health.
CONCLUSION: South African community characteristics and caregivers, in particular
male caregivers, are integral to child and caregiver mental health. Future
research should examine the impact of interventions that mobilize community and
caregiver supports for children's prosocial behavior and mental health.
PMID- 28401036
TI - Anomalous Origin of the Left Pulmonary Artery: Hemi-Truncus Arteriosus.
AB - Hemi-truncus arteriosus is a rare congenital cardiovascular malformation. It
usually presents in infancy and leads to development of progressive pulmonary
vascular disease, heart failure, and death. We report a case of hemi truncus
arteriosus in a 12-day-old neonate who was successfully managed at our institute.
PMID- 28401035
TI - Development and Application of Human Renal Proximal Tubule Epithelial Cells for
Assessment of Compound Toxicity.
AB - Kidney toxicity is a major problem both in drug development and clinical
settings. It is difficult to predict nephrotoxicity in part because of the lack
of appropriate in vitro cell models, limited endpoints, and the observation that
the activity of membrane transporters which plays important roles in
nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not
taken into account. We developed a new cell model using pseudo-immortalized human
primary renal proximal tubule epithelial cells. This cell line (SA7K) was
characterized by the presence of proximal tubule cell markers as well as several
functional properties, including transporter activity and response to a few well
characterized nephrotoxicants. We subsequently evaluated a group of potential
nephrotoxic compounds in SA7K cells and compared them to a commonly used human
immortalized kidney cell line (HK-2). Cells were treated with test compounds and
three endpoints were analyzed, including cell viability, apoptosis and
mitochondrial membrane potential. The results showed that most of the known
nephrotoxic compounds could be detected in one or more of these endpoints. There
were sensitivity differences in response to several of the chemicals between HK-2
and SA7K cells, which may relate to differences in expressions of key
transporters or other components of nephrotoxicity pathways. Our data suggest
that SA7K cells appear as promising for the early detection of renal toxicants.
PMID- 28401034
TI - Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease
Pathogenesis and Therapeutic Development.
AB - Wolman disease (WD) and cholesteryl ester storage disease (CESD) are lysosomal
storage diseases (LSDs) caused by a deficiency in lysosomal acid lipase (LAL) due
to mutations in the LIPA gene. This enzyme is critical to the proper degradation
of cholesterol in the lysosome. LAL function is completely lost in WD while some
residual activity remains in CESD. Both are rare diseases with an incidence rate
of less than 1/100,000 births for WD and approximate 2.5/100,000 births for CESD.
Clinical manifestation of WD includes hepatosplenomegaly, calcified adrenal
glands, severe malabsorption and a failure to thrive. As in CESD, histological
analysis of WD tissues reveals the accumulation of triglycerides (TGs) and
esterified cholesterol (EC) in cellular lysosomes. However, the clinical
presentation of CESD is less severe and more variable than WD. This review is to
provide an overview of the disease pathophysiology and the current state of
therapeutic development for both of WD and CESD. The review will also discuss the
application of patient derived iPSCs for further drug discovery.
PMID- 28401037
TI - Female Epispadias Presenting as Urinary Incontinence.
AB - Isolated female epispadias without bladder exstrophy is a rare congenital anomaly
affecting 1 in 484,000 females. The presenting features of female epispadias are
urinary incontinence and abnormal anatomical features. A 6-year-old girl
presented with primary urinary incontinence who on physical examination had a
bifid clitoris and labia minora. The vagina and hymen were normal. Voiding
cystourethrogram showed no reflux and a funnel shaped proximal urethra. With the
diagnosis of isolated female epispadias, one-stage reconstruction of the urethra,
bladder neck, labia minora and clitoris was performed.
PMID- 28401038
TI - Ileal Trichobezoar Presenting as Intestinal Obstruction and Peritonitis.
AB - Trichobezoar is less common in boys. We are reporting a case of isolated ileal
trichobezoars in a 4-year old boy causing intestinal obstruction and gut ischemia
with perforation and peritonitis. The case was managed surgically with ileal
resection and anastomosis. Postoperative period was uneventful.
PMID- 28401039
TI - Two Cases of Massively Prolapsed Patent Vitellointestinal Duct.
AB - Patent vitellointestinal duct (PVID) is a benign congrnital anomaly ususally
presenting with fecal discharge from the umbilicus. In this report, we describe
two cases of PVID presented with massive bowel prolapse through the PVID and
signs of intestinal obstruction. Surgery revealed prolapse of the ileal
intussusceptum through the PVID. Both of the babies were sucssesfully managed
with surgery.
PMID- 28401040
TI - Sewing Needle Penetration into Thorax: What Might be the Cause?
PMID- 28401041
TI - Stromme Syndrome: New Clinical Features.
PMID- 28401042
TI - Intrauterine Intussusception Leading to Ileal Atresia in a Premature Baby.
PMID- 28401043
TI - Lumbo-Costo-Vertebral Syndrome: An Iceberg with Tip of Hernia and Body of Spinal
and Neurological Malformations.
PMID- 28401044
TI - Identity and schizophrenia: Who do I want to be?
AB - Many individuals with schizophrenia have occasional difficulty defining both to
themselves and to others who they truly are. Perhaps for this reason they make
attempts to change core aspects of themselves. These attempts may be delusional,
but are too often unjustly dismissed as delusional before the potential value of
the change is considered. Instead of facilitation, obstacles are placed in the
way of hoped-for body modifications or changes of name or of religious faith.
This paper discusses the various changes of identity sometimes undertaken by
individuals with schizophrenia who may or may not be deluded. Ethical and
clinical ramifications are discussed. The recommendation is made that, when
clinicians respond to requests for help with identity change, safety needs to be
the main consideration.
PMID- 28401045
TI - Differences between British and Japanese perspectives on forensic mental health
systems: A preliminary study.
AB - AIM: To clarify the differences in views on forensic mental health (FMH) systems
between the United Kingdom and Japan. METHODS: We conducted a series of semi
structured interviews with six leading forensic psychiatrists. Based on a
discussion by the research team, we created an interview form. After we finished
conducting all the interviews, we qualitatively analyzed their content. RESULTS:
In the United Kingdom the core domain of FMH was risk assessment and management;
however, in Japan, the core domain of FMH was psychiatric testimony. In the
United Kingdom, forensic psychiatrists were responsible for ensuring public
safety, and psychopathy was identified as a disease but deemed as not suitable
for medical treatment. On the other hand, in Japan, psychopathy was not
considered a mental illness. CONCLUSION: In conclusion, there are considerable
differences between the United Kingdom and Japan with regard to the concepts of
FMH. Some ideas taken from both cultures for better FMH practice were suggested.
PMID- 28401047
TI - Neuroimaging studies of cognitive remediation in schizophrenia: A systematic and
critical review.
AB - AIM: To examine the effects of cognitive remediation therapies on brain
functioning through neuroimaging procedures in patients with schizophrenia.
METHODS: A systematic, computerised literature search was conducted in the
PubMed/Medline and PsychInfo databases. The search was performed through February
2016 without any restrictions on language or publication date. The search was
performed using the following search terms: [("cogniti*" and "remediation" or
"training" or "enhancement") and ("fMRI" or "MRI" or "PET" or "SPECT") and
(schizophrenia or schiz*)]. The search was accompanied by a manual online search
and a review of the references from each of the papers selected, and those papers
fulfilling our inclusion criteria were also included. RESULTS: A total of 101
studies were found, but only 18 of them fulfilled the inclusion criteria. These
studies indicated that cognitive remediation improves brain activation in
neuroimaging studies. The most commonly reported changes were those that involved
the prefrontal and thalamic regions. Those findings are in agreement with the
hypofrontality hypothesis, which proposes that frontal hypoactivation is the
underlying mechanism of cognitive impairments in schizophrenia. Nonetheless,
great heterogeneity among the studies was found. They presented different
hypotheses, different results and different findings. The results of more recent
studies interpreted cognitive recovery within broader frameworks, namely, as
amelioration of the efficiency of different networks. Furthermore, advances in
neuroimaging methodologies, such as the use of whole-brain analysis,
tractography, graph analysis, and other sophisticated methodologies of data
processing, might be conditioning the interpretation of results and generating
new theoretical frameworks. Additionally, structural changes were described in
both the grey and white matter, suggesting a neuroprotective effect of cognitive
remediation. Cognitive, functional and structural improvements tended to be
positively correlated. CONCLUSION: Neuroimaging studies of cognitive remediation
in patients with schizophrenia suggest a positive effect on brain functioning in
terms of the functional reorganisation of neural networks.
PMID- 28401046
TI - Functional neuroanatomy in panic disorder: Status quo of the research.
AB - AIM: To provide an overview of the current research in the functional
neuroanatomy of panic disorder. METHODS: Panic disorder (PD) is a frequent
psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive
neuroanatomical model of PD, which suggested that fear- and anxiety-related
responses are mediated by a so-called "fear network" which is centered in the
amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal
gray region, locus coeruleus and other brainstem sites. We performed a systematic
search by the electronic database PubMed. Thereby, the main focus was laid on
recent neurofunctional, neurostructural, and neurochemical studies (from the
period between January 2012 and April 2016). Within this frame, special attention
was given to the emerging field of imaging genetics. RESULTS: We noted that many
neuroimaging studies have reinforced the role of the "fear network" regions in
the pathophysiology of panic disorder. However, recent functional studies suggest
abnormal activation mainly in an extended fear network comprising brainstem,
anterior and midcingulate cortex (ACC and MCC), insula, and lateral as well as
medial parts of the prefrontal cortex. Interestingly, differences in the amygdala
activation were not as consistently reported as one would predict from the
hypothesis of Gorman et al (2000). Indeed, amygdala hyperactivation seems to
strongly depend on stimuli and experimental paradigms, sample heterogeneity and
size, as well as on limitations of neuroimaging techniques. Advanced
neurochemical studies have substantiated the major role of serotonergic,
noradrenergic and glutamatergic neurotransmission in the pathophysiology of PD.
However, alterations of GABAergic function in PD are still a matter of debate and
also their specificity remains questionable. A promising new research approach is
"imaging genetics". Imaging genetic studies are designed to evaluate the impact
of genetic variations (polymorphisms) on cerebral function in regions critical
for PD. Most recently, imaging genetic studies have not only confirmed the
importance of serotonergic and noradrenergic transmission in the etiology of PD
but also indicated the significance of neuropeptide S receptor, CRH receptor,
human TransMEMbrane protein (TMEM123D), and amiloride-sensitive cation channel 2
(ACCN2) genes. CONCLUSION: In light of these findings it is conceivable that in
the near future this research will lead to the development of clinically useful
tools like predictive biomarkers or novel treatment options.
PMID- 28401048
TI - Attention-deficit/hyperactivity disorder and suicide: A systematic review.
AB - AIM: To investigate suicidality and attention-deficit/hyperactivity disorder
(ADHD), this paper aims to systematically review the literature as an extension
of previous reviews. METHODS: We searched five databases (Ovid MEDLINE,
Psychinfo, PubMed, Scopus, Web of Science) with two categories of search terms:
(1) suicide; suicidal; suicide behavior; suicide attempt; suicidal thought; and
(2) ADHD. RESULTS: The search resulted 26 articles. There is a positive
association between ADHD and suicidality in both sexes and in all age groups.
Comorbid disorders mediate between suicidality and ADHD. CONCLUSION: Recognizing
ADHD, comorbid conditions and suicidality is important in prevention.
PMID- 28401049
TI - Consequences of bullying victimization in childhood and adolescence: A systematic
review and meta-analysis.
AB - AIM: To identify health and psychosocial problems associated with bullying
victimization and conduct a meta-analysis summarizing the causal evidence.
METHODS: A systematic review was conducted using PubMed, EMBASE, ERIC and
PsycINFO electronic databases up to 28 February 2015. The study included
published longitudinal and cross-sectional articles that examined health and
psychosocial consequences of bullying victimization. All meta-analyses were based
on quality-effects models. Evidence for causality was assessed using Bradford
Hill criteria and the grading system developed by the World Cancer Research Fund.
RESULTS: Out of 317 articles assessed for eligibility, 165 satisfied the
predetermined inclusion criteria for meta-analysis. Statistically significant
associations were observed between bullying victimization and a wide range of
adverse health and psychosocial problems. The evidence was strongest for causal
associations between bullying victimization and mental health problems such as
depression, anxiety, poor general health and suicidal ideation and behaviours.
Probable causal associations existed between bullying victimization and tobacco
and illicit drug use. CONCLUSION: Strong evidence exists for a causal
relationship between bullying victimization, mental health problems and substance
use. Evidence also exists for associations between bullying victimization and
other adverse health and psychosocial problems, however, there is insufficient
evidence to conclude causality. The strong evidence that bullying victimization
is causative of mental illness highlights the need for schools to implement
effective interventions to address bullying behaviours.
PMID- 28401050
TI - The New Rome IV Criteria for Functional Gastrointestinal Disorders in Infants and
Toddlers.
AB - Functional gastrointestinal disorders (FGIDs) are common worldwide and cover a
wide range of disorders attributable to the gastrointestinal tract that cannot be
explained by structural or biochemical abnormalities. The diagnosis of these
disorders relies on the symptom-based Rome criteria. In 2016 the Rome criteria
were revised for infants/toddlers and for children and adolescents. In this
review, we discuss the novel Rome IV criteria for infants and toddlers. The
criteria for infant colic were drastically changed, whereas only minor changes
were made for regurgitation, cyclic vomiting syndrome, functional diarrhea,
infant dyschezia and functional constipation. In addition to this, the new Rome
IV discusses underlying mechanisms of pain in infants and toddlers, including the
neuro-development of nociceptive and pain pathways, the various factors that are
involved in pain experience, and methods of pain assessment in infants and
toddlers is essential for the clinician who encounters functional pain in this
age group. Overall, the Rome IV criteria have become more distinctive for all
disorders in order to improve the process of diagnosing pediatric FGIDs.
PMID- 28401051
TI - Surgery in Pediatric Crohn's Disease: Indications, Timing and Post-Operative
Management.
AB - Pediatric onset Crohn's disease (CD) tends to have complicated behavior
(stricture or penetration) than elderly onset CD at diagnosis. Considering the
longer duration of the disease in pediatric patients, the accumulative chance of
surgical treatment is higher than in adult onset CD patients. Possible operative
indications include perianal CD, intestinal stricture or obstruction, abdominal
abscess or fistula, intestinal hemorrhage, neoplastic changes and medically
untreatable inflammation. Growth retardation is an operative indication only for
pediatric patients. Surgery can affect a patient's clinical course, especially
for pediatric CD patient who are growing physically and mentally, so the decision
should be made by careful consideration of several factors. The complex and
diverse clinical conditions hinder development of a systemized treatment
algorithm. Therefore, timing of surgery in pediatric CD patients should be
determined with individualized approach by an experienced and well organized
multidisciplinary inflammatory bowel disease team. Best long-term outcomes will
require proactive post-operative monitoring and therapeutic modifications
according to the conditions.
PMID- 28401052
TI - Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSSTM) as a Predictor
for Cow's Milk Related Symptoms.
AB - PURPOSE: The diagnosis of cow's milk (CM) allergy is a challenge. The Cow's Milk
related-Symptom-Score (CoMiSSTM) was developed to offer primary health care
providers a reliable diagnostic tool for CM related symptoms. The predictive
prospective value of the CoMiSSTM was evaluated in three clinical trials.
METHODS: Pooled analyses of the three studies were conducted based on regressing
the results of the month-1 challenge test on the month-1 CoMiSSTM, adjusting for
baseline CoMiSSTM using a logistic regression model. In addition a logistic
regression model was also fitted to the month-1 challenge test result with the
change in CoMiSSTM from baseline as a predictor. RESULTS: Results suggest that
infants having a low CoMiSSTM (median, 5) after 1 month dietary treatment free
from intact CM protein have a significant risk of having a positive challenge
test (odds ratio, 0.83; 95% confidence interval, 0.75-0.93; p=0.002). Pooled data
suggest that the change in CoMiSSTM from baseline to month-1 can predict CM
related symptoms as a confirmed diagnosis according to the challenge test at
month-1. However, in order to validate such a tool, infants without CM related
symptoms would also need to be enrolled in a validation trial. A concern is that
it may not be ethical to expose healthy infants to a therapeutic formula and a
challenge test. CONCLUSION: Pooled data analysis emphasizes that the CoMiSSTM has
the potential to be of interest in infants suspected to have CM-related-symptoms.
A prospective validation trial is needed.
PMID- 28401053
TI - Comparison of Percutaneous Endoscopic Gastrostomy and Surgical Gastrostomy in
Severely Handicapped Children.
AB - PURPOSE: Gastrostomy is commonly used procedures to provide enteral nutrition
support for severely handicapped patients. This study aimed to identify and
compare outcomes and complications associated with percutaneous endoscopic
gastrostomy (PEG) and surgical gastrostomy (SG). METHODS: A retrospective chart
review of 51 patients who received gastrostomy in a single tertiary hospital from
January 2000 to May 2016 was performed. We analyzed the patients and the
complications caused by the procedures. RESULTS: Among the 51 patients, 26 had
PEG and 25 had SG. Four cases in the SG group had fundoplication for
gastroesophageal reflux disease. PEG and SG groups were followed up for an
average of 29 months and 44 months. Major complications occurred in 19.2% of
patients in the PEG group and 20.0% in the SG group, but significant differences
between the groups were not observed. Minor complications occurred in 15.4% of
patients in the PEG group and 52.0% in the SG group. Minor complications were
significantly lower in the PEG group than in the SG group (p=0.006). The average
use of antibiotics in the PEG and SG groups was 6.2 days and 15.7 days (p=0.002).
Thirteen patients died of underlying disease but not related to gastrostomy, and
only one patient died due to complications associated with general anesthesia.
CONCLUSION: The duration of antibiotics use and incidence of minor complications
were significantly lower in the PEG group than those in the SG group. Early PEG
could be recommended for nutritional supports.
PMID- 28401054
TI - Single Center Experience with Gastrostomy Insertion in Pediatric Patients: A 10
Year Review.
AB - PURPOSE: This study was performed to review the outcomes of gastrostomy insertion
in children at our institute during 10 years. METHODS: A retrospective chart
review was performed on 236 patients who underwent gastrostomy insertion from
October 2005 to March 2015. We used our algorithm to select the least invasive
method for gastrostomy insertion for each patient. Long-term follow-up was
performed to analyze complications related to the method of gastrostomy
insertion. RESULTS: Out of 236 patients, 120 underwent endoscopic gastrostomy, 79
had laparoscopic gastrostomy, and 37 had open gastrostomy procedures. The total
major complication rates for endoscopic gastrostomy insertion, laparoscopic
gastrostomy insertion, and open gastrostomy were 9.2%, 8.9%, and 8.1%,
respectively. The most common major complication was gastroesophageal reflux
requiring Nissen fundoplication (3.8%), and other complications included
peritonitis (1.3%), hiatal hernia (1.3%), and bowel perforation (0.8%).
Gastrostomy removal was successful in 8.6% and 5.0% of patients in the endoscopic
and surgical gastrostomy groups, respectively. Gastrocutaneous fistula occurred
in 60% of surgically inserted cases, requiring a second operation. CONCLUSION:
This retrospective study was performed to review the outcome of gastrostomy
insertion, as well as to introduce an algorithm that can be used for future
cases. Further studies should be conducted to make a consensus on choosing the
most appropriate method for gastrostomy insertion.
PMID- 28401055
TI - Effect of the Baseline Vitamin D Level on Growth Outcome in Pediatric Crohn
Disease.
AB - PURPOSE: Vitamin D deficiency is common in Crohn disease (CD). The aim of the
study was to examine the prevalence of vitamin D deficiency and evaluate the
association between vitamin D status and growth outcome in Korean pediatric CD
patients. METHODS: In this retrospective study, 17 children younger than 18 years
old diagnosed with CD were enrolled and their serum 25-hydroxy vitamin D
(25[OH]D) was checked between 2011 and 2015. We categorized the patients into two
groups, Group 1 and Group 2. Group 1 included patients with serum 25(OH)D levels
below 10 ng/mL, and Group 2 was for patients with a 25(OH)D serum levels between
10 ng/mL and 30 ng/mL. The z-scores for height (Htz), weight (Wtz), and body mass
index (BMIz) were measured at baseline, 6 months, and 12 months. RESULTS: The
mean serum 25(OH)D levels of the total 65 CD patients and 17 enrolled patients
were 15.64+/-6.9 ng/mL and 13.1+/-5.1 ng/mL, respectively. There was no
correlation at the beginning of the study between vitamin D level and growth
parameters (Htz, Wtz, BMIz) or other variables including laboratory data and
Pediatric Crohn Disease Activity Index. The Htz, Wtz, and BMIz in Group 1 showed
no significant improvement at 6 months and 12 months follow-up. In Group 2, Wtz
and BMIz showed significant improvements sustained until 12 months of follow-up.
Htz showed no significant improvement at 6 months but there was significant
improvement at 12 months. CONCLUSION: It seems that baseline vitamin D status
affects growth outcome in pediatric CD.
PMID- 28401056
TI - Effect of Metronidazole in Infants with Bowel Habit Change: Irrelative to the
Clostridium difficile Colonization.
AB - PURPOSE: Clinical symptoms associated with Clostridium difficile infection (CDI)
can vary widely. Carrier state without apparent symptoms is relatively common
during infancy. The objective of this study was to determine the association of
C. difficile colonization with bowel habit change and the effect of C. difficile
colonization treatment on restoration of normal bowel habit. METHODS: Between
2006 and 2014, infants at 1 to 12 months of age with diarrhea for more than 2
weeks who did not improve with conservative care were recruited from Gachon
University Gil Medical Center. Infants who were followed up for at least 7 days
were included. The presence or absence of C. difficile colonization, effect of
metronidazole, and other medical records were reviewed. To determine the
association between CDI and bowel habit change, logistic regression analysis was
used. RESULTS: Of a total of 126 infants, 74 (58.7%) were male patients. Of the
126 patients, 27 (21.4%) had C. difficile colonization. Significant (p<0.05) risk
factors for C. difficile colonization included artificial milk feeding (odds
ratio [OR], 4.310; 95% confidence interval [CI], 1.564-11.878), prior rotavirus
vaccination (OR, 4.322; 95% CI, 1.018-18.349), and antibiotic use (OR, 4.798; 95%
CI, 1.430-16.101). There was improvement in bowel habit after metronidazole
therapy (OR, 0.34; 95% CI, 0.15-0.79; p<0.05), regardless of the presence or
absence of C. difficile colonization. CONCLUSION: There was no significant
correlation between bowel habit change and C. difficile colonization during
infancy. However, metronidazole can be used as an optional method to manage
functional gastrointestinal disorders.
PMID- 28401057
TI - Intestinal Hypoganglionosis Leading to Intestinal Failure and the Compassionate
Use of OmegavenTM.
AB - Intestinal hypoganglionosis is a rare innervation disorder that provides numerous
nutritional, medical and surgical challenges. In this case report, we present a
case of a newborn with intestinal hypoganglionosis leading to intestinal failure
and intestinal failure-associated liver disease who responded to OmegavenTM, a
fat emulsion comprised of omega-3 fatty acids. OmegavenTM has been shown to be
beneficial in the management of cholestatic liver injury. Clinical success with
OmegavenTM was seen in this patient with a clear decrease in aspartate
aminotransferase, alanine aminotransferase, alkaline phosphatase and complete
resolution of cholestasis with a direct bilirubin of zero within two weeks of
initiation of OmegavenTM. No current guidelines for the diagnosis and management
of hypoganglionosis are available. We recommend a multidisciplinary approach and
the use of novel therapies such as fat emulsions composed of omega-3 fatty acids
for improved patient outcomes. Appropriate compassionate use protocols should be
obtained from the Food and Drug Administration prior to initiation of OmegavenTM.
PMID- 28401058
TI - A Rare Cause of Recurrent Acute Pancreatitis in a Child: Isovaleric Acidemia with
Novel Mutation.
AB - Recurrent acute pancreatic attacks is a rare clinical condition (2-5% of all
acute pancreatis) in children and is mainly idiopathic in most cases. Sometimes
it may be associated with congenital anomalies, metabolic diseases or hereditary
conditions. Isovaleric acidemia (IVA) is a rare autosomal recessive amino acid
metabolism disorder associated with isovaleryl coenzyme A dehydrogenase
deficiency presenting the clinical findings such metabolic acidosis with
increased anion gap, hyperammonemia, ketonemia, hypoglycemia, "the odor of sweaty
feet," abdominal pain, vomiting, feeding intolerance, shock and coma. Recurrent
acute pancreatitis associated with IVA have been rarely reported. Herein; we
report a child who admitted with recurrent acute pancreatic attacks and had the
final diagnosis of IVA. Mutation analysis revealed a novel homozygous mutation of
(p.E117K [c.349G>A]) in the IVA gene. Organic acidemias must kept in mind in the
differential diagnosis of recurrent acute pancreatic attacks in children.
PMID- 28401059
TI - Bannayan-Riley-Ruvalcaba Syndrome in a Patient with a PTEN Mutation Identified by
Chromosomal Microarray Analysis: A Case Report.
AB - Bannayan-Riley-Ruvalcaba syndrome (BRRS) is one of the phosphatase and tensin
homolog hamartoma tumor syndrome with a PTEN gene mutation. It is a rare dominant
autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal
polyps, and developmental delay. Diagnosing this syndrome is important, because
it may represent the pediatric phenotype of Cowden syndrome, in which there is an
increased risk for malignant tumors in children. Until now, the prevalence of
BRRS is unknown. Several dozen cases have been reported in the medical
literature, but no case has been reported in Korea. Here we report a case of a 19
year-old girl who was diagnosed with BRRS because of macrocephaly, intellectual
disability, and intestinal polyps. Her mother had similar findings and a PTEN
mutation. Neither patient had mutations detected by conventional mutation
detection techniques, but a PTEN gene deletion was demonstrated by chromosomal
microarray analysis.
PMID- 28401061
TI - Transcription Factor GFI1B in Health and Disease.
AB - Many human diseases arise through dysregulation of genes that control key cell
fate pathways. Transcription factors (TFs) are major cell fate regulators
frequently involved in cancer, particularly in leukemia. The GFI1B gene, coding a
TF, was identified by sequence homology with the oncogene growth factor
independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers
and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is
essential for neutrophil differentiation in mice. In humans, GFI1 mutations are
associated with severe congenital neutropenia. Gfi1 is also required for B and T
lymphopoiesis. However, knockout mice have demonstrated that Gfi1b is required
for development of both erythroid and megakaryocytic lineages. Consistent with
this, human mutations of GFI1B produce bleeding disorders with low platelet count
and abnormal function. Loss of Gfi1b in adult mice increases the absolute numbers
of hematopoietic stem cells (HSCs) that are less quiescent than wild-type HSCs.
In keeping with this key role in cell fate, GFI1B is emerging as a gene involved
in cancer, which also includes solid tumors. In fact, abnormal activation of
GFI1B and GFI1 has been related to human medulloblastoma and is also likely to be
relevant in blood malignancies. Several pieces of evidence supporting this
statement will be detailed in this mini review.
PMID- 28401060
TI - Therapeutic Targeting of Histone Modifications in Adult and Pediatric High-Grade
Glioma.
AB - Recent exciting work partly through The Cancer Genome Atlas has implicated
epigenetic mechanisms including histone modifications in the development of both
pediatric and adult high-grade glioma (HGG). Histone lysine methylation has
emerged as an important player in regulating gene expression and chromatin
function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3
variants and the subject of posttranslational histone modifications, as it can be
both methylated and acetylated. In pediatric HGG, two critical single-point
mutations occur in the H3F3A gene encoding the regulatory histone variant H3.3.
These mutations occur at lysine (K) 27 (K27M) and glycine (G) 34 (G34R/V), both
of which are involved with key regulatory posttranscriptional modifications.
Therefore, these mutations effect gene expression, cell differentiation, and
telomere maintenance. In recent years, alterations in histone acetylation have
provided novel opportunities to explore new pharmacological targeting, with
histone deacetylase (HDAC) overexpression reported in high-grade, late-stage
proliferative tumors. HDAC inhibitors have shown promising therapeutic potential
in many malignancies. This review focuses on the epigenetic mechanisms
propagating pediatric and adult HGGs, as well as summarizing the current advances
in clinical trials using HDAC inhibitors.
PMID- 28401062
TI - Genomic Insights into Diffuse Intrinsic Pontine Glioma.
AB - Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric
brainstem tumor with a peak incidence in middle childhood and a median survival
of less than 1 year. The dismal prognosis associated with DIPG has been
exacerbated by the failure of over 250 clinical trials to meaningfully improve
survival compared with radiotherapy, the current standard of care. The
traditional practice to not biopsy DIPG led to a scarcity in available tissue
samples for laboratory analysis that till recently hindered therapeutic advances.
Over the past few years, the acquisition of patient derived tumor samples through
biopsy and autopsy protocols has led to distinct breakthroughs in the
identification of key oncogenic drivers implicated in DIPG development.
Aberrations have been discovered in critical genetic drivers including histone
H3, ACVR1, TP53, PDGFRA, and Myc. Mutations, previously not identified in other
malignancies, highlight DIPG as a distinct biological entity. Identification of
novel markers has already greatly influenced the direction of preclinical
investigations and offers the exciting possibility of establishing biologically
targeted therapies. This review will outline the current knowledge of the genomic
landscape related to DIPG, overview preclinical investigations, and reflect how
biological advances have influenced the focus of clinical trials toward targeted
therapies.
PMID- 28401063
TI - SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G.
AB - The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a
surface-associated receptor with a particular affinity for mini-plasminogen, a
cleavage product of the broad-spectrum serine protease plasmin. Here, we report
that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity.
The ability of a particular S. canis isolate to bind to IgG significantly
correlates with a scm-positive phenotype, suggesting a dominant role of SCM as an
IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S.
gordonii and Western Blot analysis with purified recombinant SCM proteins
confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM
IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs
derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and
goats. Similar to other streptococcal IgG-binding proteins, the interaction
between SCM and IgG occurs via the conserved Fc domain and is, therefore, non
opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial
surface specifically prevents opsonization by C1q, which might constitute another
anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of
different truncated SCM fragments defined a region of 52 amino acids located in
the central part of the mature SCM protein which is important for IgG binding.
This binding region is highly conserved among SCM proteins derived from different
S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes
and S. dysgalactiae sub. equisimilis, respectively. In summary, we present an
additional role of SCM in the pathogen-host interaction of S. canis. The detailed
analysis of the SCM-IgG interaction should contribute to a better understanding
of the complex roles of M proteins in streptococcal pathogenesis.
PMID- 28401064
TI - Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation
Increases Hypoxia Inducible Factor-1alpha to Promote Loss of Cyclin D1 and G0/G1
Cell Cycle Arrest in Human Gastric Cells.
AB - Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked
to the development of several gastric pathologies, such as gastritis, peptic
ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many
signaling pathways, resulting in contradictory responses that favor both
proliferation and apoptosis. Consistent with such observations, H. pylori
activates routes associated with cell cycle progression and cell cycle arrest. H.
pylori infection also induces the hypoxia-induced factor HIF-1alpha, a
transcription factor known to promote expression of genes that permit metabolic
adaptation to the hypoxic environment in tumors and angiogenesis. Recently,
however, also roles for HIF-1alpha in the repair of damaged DNA and inhibition of
gene expression were described. Here, we investigated signaling pathways induced
by H. pylori in gastric cells that favor HIF-1alpha expression and the
consequences thereof in infected cells. Our results revealed that H. pylori
promoted PI3K/mTOR-dependent HIF-1alpha induction, HIF-1alpha translocation to
the nucleus, and activity as a transcription factor as evidenced using a reporter
assay. Surprisingly, however, transcription of known HIF-1alpha effector genes
evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH),
statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance
transcription (VEGFA), but in an HIF-1alpha-independent manner, as quantified by
PCR analysis in cells with shRNA-mediated silencing of HIF-1alpha. Instead, HIF
1alpha knockdown facilitated G1/S progression and increased Cyclin D1 protein
half-life, via a post-translational pathway. Taken together, these findings link
H. pylori-induced PI3K-mTOR activation to HIF-1alpha induced G0/G1 cell cycle
arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1alpha is identified here as
a mediator between survival and cell cycle arrest signaling activated by H.
pylori infection.
PMID- 28401065
TI - A Long Journey Ahead: Long Non-coding RNAs in Bacterial Infections.
AB - Bacterial pathogens have coevolved with their hosts and acquired strategies to
circumvent defense mechanisms of host cells. It was shown that bacteria interfere
with the expression of mammalian microRNAs to modify immune signaling, autophagy,
or the apoptotic machinery. Recently, a new class of regulatory RNAs, long non
coding RNAs (lncRNAs), was reported to have a pivotal role in the regulation of
eukaryotic gene expression. A growing body of literature reports on specific
involvement of lncRNAs in the host cell response toward bacterial infections.
This mini review summarizes recent data that focuses on lncRNA function in host
cells during bacterial infection and provides a perspective where future research
in this regard may be going.
PMID- 28401066
TI - Importance of Metabolic Adaptations in Francisella Pathogenesis.
AB - Francisella tularensis is a highly infectious Gram-negative bacterium and the
causative agent of the zoonotic disease tularemia. This bacterial pathogen can
infect a broad variety of animal species and can be transmitted to humans in
numerous ways with various clinical outcomes. Although, Francisella possesses the
capacity to infect numerous mammalian cell types, the macrophage constitutes the
main intracellular niche, used for in vivo bacterial dissemination. To survive
and multiply within infected macrophages, Francisella must imperatively escape
from the phagosomal compartment. In the cytosol, the bacterium needs to control
the host innate immune response and adapt its metabolism to this nutrient
restricted niche. Our laboratory has shown that intracellular Francisella mainly
relied on host amino acid as major gluconeogenic substrates and provided evidence
that the host metabolism was also modified upon Francisella infection. We will
review here our current understanding of how Francisella copes with the available
nutrient sources provided by the host cell during the course of infection.
PMID- 28401067
TI - A Nuclease from Streptococcus mutans Facilitates Biofilm Dispersal and Escape
from Killing by Neutrophil Extracellular Traps.
AB - Streptococcus mutans is the primary etiologic agent of dental caries and
occasionally infective endocarditis, with the ability to form biofilms and
disperse cells into distal sites to exacerbate and spread infection. In this
study, we identified a nuclease (DeoC) as a S. mutans biofilm dispersal
modulating factor through microarray analysis. In vitro assays revealed a
dispersal defect of a deoC deletion mutant, and functional studies with purified
protein were indicative of the biofilm dispersal activity of DeoC. Neutrophils
are a key host response factor restraining bacterial spreading through the
formation of neutrophil extracellular traps (NETs), which consist of a nuclear
DNA backbone associated with antimicrobial peptides. Therefore, we hypothesized
that the dispersed S. mutans might utilize DeoC to degrade NETs and escape
killing by the immune system. It was found that S. mutans induced NET formation
upon contact with neutrophils, while the presence of NETs in turn enhanced the
deoC expression of S. mutans. Fluorescence microscopy inspection showed that deoC
deletion resulted in a decreased NET degradation ability of S. mutans and
enhanced susceptibility to neutrophil killing. Data obtained from this study
assigned two important roles for DeoC in S. mutans: contributing to the spread of
infection through mediating biofilm dispersal, and facilitating the escape of S.
mutans from neutrophil killing through NET degradation.
PMID- 28401068
TI - Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T
Cells from Patients with Chronic Hepatitis B Virus Infection.
AB - T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was
up-regulated on viral specific T cells and contributed to T cells exhaustion
during chronic hepatitis B virus (HBV) infection. However, modulation of Tim-3
expression was still not fully elucidated. To evaluate the potential viral and
inflammatory factors involved in the inductor of Tim-3 expression on T cells, 76
patients with chronic HBV infection (including 40 chronic hepatitis B [CHB] and
36 asymptomatic HBV carriers [AsC]) and 40 of normal controls (NCs) were enrolled
in this study. Tim-3 expressions on CD4+ and CD8+ T cells were assessed in
response to HBV-encoding antigens, HBV peptide pools, and common gamma-chain
(gammac) cytokines stimulation by flow cytometry. HBV peptides and anti-CD3/CD28
directly induced Tim-3 expression on T cells. gammac cytokines also drive Tim-3
up-regulations on both CD4+ and CD8+ T cells in patients with chronic HBV
infection. However, gammac cytokines did not enhance the Tim-3 inductions by
either anti-CD3/CD28 or HBV peptides stimulation. Furthermore, gammac cytokines
mediated Tim-3 induction could not be abrogated by gammac cytokine receptor
neutralizing antibodies. The current results suggested that elevation of Tim-3
expression on T cells could be regulated by both antigen-dependent and
independent manner in patients with chronic HBV infection. The role of gammac
cytokines in modulation of inhibitory pathway might be evaluated as
immunotherapies in humans.
PMID- 28401069
TI - A Novel Restraint Device for Injection of Galleria mellonella Larvae that
Minimizes the Risk of Accidental Operator Needle Stick Injury.
AB - Larvae of the insect Galleria mellonella are increasingly being used for studying
pathogenic microbes and their virulence mechanisms, and as a rapid model for
screening novel antimicrobial agents. The larvae (waxworms) are most frequently
infected by injection of pathogenic organisms into the haemocoel through the
insect's prolegs. The mostly widely used method for restraining the waxworms for
injection is by grasping them between the operator's fingers, which puts the
operator at risk of needle stick injury, an important consideration when working
with highly pathogenic and/or drug-resistant microorganisms. While use of a stab
proof glove can reduce this risk of injury, it does so at the loss of manual
dexterity and speed, resulting in a more labor-intensive, and cumbersome assay.
We describe a simple cost effective device (the so-called "Galleria Grabber") for
restraining waxworms for injection that keeps the operator's fingers clear of the
needle thus reducing the risk of injury.
PMID- 28401070
TI - Simple and Easy to Perform Preimplantation Genetic Diagnosis for beta-thalassemia
Major Using Combination of Conventional and Fluorescent Polymerase Chain
Reaction.
AB - BACKGROUND: Thalassemias are the most common monogenic disorders in many
countries throughout the world. The best practice to control the prevalence of
the disease is prenatal diagnosis (PND) services. Extensive practicing of PND
proved effective in reducing new cases but on the other side of this success high
abortion rate is hided, which ethically unfair and for many couples, especially
with a previous experience of a therapeutic abortion, or moral concerns, is not a
suitable choice. Preimplantation genetic diagnosis (PGD) is a strong alternative
to conventional PND. At present PGD is the only abortion free fetal diagnostic
process. Considering the fact that there are more than 6000 single gene disorders
affecting approximately 1 in 300 live-births, the medical need for PGD services
is significant. MATERIALS AND METHODS: In the present study development of a PGD
protocol for a thalassemia trait couple using nested multiplex fluorescent
polymerase chain reaction (PCR) for the combination of polymorphic linked short
tandem repeat (STR) markers and thalassemia mutations is described. Restriction
fragment length polymorphism used to discriminate between wild and mutated
alleles. RESULTS: In PGD clinical cycle, paternal and maternal alleles for
D11S988 and D11S1338 STR markers were segregated as it was expected. PCR product
for IVSII-1 mutation was subsequently digested with BtscI restriction enzyme to
differentiate normal allele from the mutant allele. The mother's mutation, being
a comparatively large deletion, was detectable through size differences on
agarose gel. CONCLUSION: The optimized single cell protocol developed and
evaluated in this study is a feasible approach for preimplantation diagnosis of
beta-thalassemia in our patients.
PMID- 28401071
TI - Identification of a New Single-nucleotide Polymorphism within the Apolipoprotein
A5 Gene, Which is Associated with Metabolic Syndrome.
AB - BACKGROUND: Metabolic syndrome (MetS) is a common disorder which is a
constellation of clinical features including abdominal obesity, increased level
of serum triglycerides (TGs) and decrease of serum high-density lipoprotein
cholesterol (HDL-C), elevated blood pressure, and glucose intolerance. The
apolipoprotein A5 (APOA5) is involved in lipid metabolism, influencing the level
of plasma TG and HDL-C. In the present study, we aimed to investigate the
associations between four INDEL variants of APOA5 gene and the MetS risk.
MATERIALS AND METHODS: In this case-control study, we genotyped 116 Iranian
children and adolescents with/without MetS by using Sanger sequencing method for
these INDELs. Then, we explored the association of INDELs with MetS risk and
their clinical components by logistic regression and one-way analysis of variance
analyses. RESULTS: We identified a novel insertion polymorphism, c. *282-283
insAG/c. *282-283 insG variant, which appears among case and control groups.
rs72525532 showed a significant difference for TG levels between various genotype
groups. In addition, there were significant associations between newly identified
single-nucleotide polymorphism (SNP) and rs72525532 with MetS risk. CONCLUSIONS:
These results show that rs72525532 and the newly identified SNP may influence the
susceptibility of the individuals to MetS.
PMID- 28401072
TI - The Investigation of Insulin Resistance in Two Groups of Epileptic Patients
Treated with Sodium Valproate and Carbamazepine.
AB - BACKGROUND: Valproic acid (VPA) is a widely used broad-spectrum antiepileptic
drug for therapy of generalized and focal epilepsies. Cross-sectional studies
have suggested that valproate treatment may be associated with hyperinsulinemia.
We decided to investigate hyperinsulinemia as a health-threatening side effect of
VPA in Iranian epileptic patients. MATERIALS AND METHODS: Body mass index (BMI),
lipid profile, fasting serum insulin, fasting blood glucose (FBS), and
homeostatic model assessment-insulin resistance (HOMA-IR) were measured in 30 VPA
treated epileptic patients and 30 controls (CBZ-treated). The Chi-square test, t
test, and Pearson correlation test were used. RESULTS: BMI was higher in VPA
group than in control group (25.7 +/- 3.5 > 21.7 +/- 4.1) (0.000 < 0.05).
Prevalence of obesity was 16.6% in VPA group that was almost the same and even
lower than general Iranian population. Serum triglyceride (TG) (150 +/- 77.2) was
higher than CBZ group (114 +/- 35.2) (P = 0.023 < 0.05). However, serum high
density lipoprotein level was lower in VPA group than controls (45.2 +/- 11.7 <
54.4 +/- 13.9) (P = 0.008 < 0.05). Serum insulin, FBS, HOMA-IR, cholesterol, and
low-density lipoprotein did not demonstrate statistically significant differences
between the two groups (P > 0.05). CONCLUSION: Despite the majority of previous
studies that are against VPA and according to our study, VPA could be prescribed
safely and it may not cause IR and its complications.
PMID- 28401074
TI - Proteus Syndrome with Arteriovenous Malformation.
AB - Proteus syndrome is a rare sporadic disorder that appears with localized
macrosomia, congenital lipomatosis, and slow flow vascular malformations,
connective tissue nevus, and epidermal nevus. There are usually some
manifestations at birth. The vascular abnormalities that have been reported in
Proteus syndrome are capillary and slow flow venous malformation. We report a
case of a 10-year-old boy with confirmed Proteus syndrome characterized by high
flow vascular malformation (arteriovenous [AV] malformation) unlike the usual
vascular malformations seen in this syndrome. This case adds a new perspective to
the established clinical findings of the Proteus syndrome.
PMID- 28401073
TI - Structural Insight into Anaphase Promoting Complex 3 Structure and Docking with a
Natural Inhibitory Compound.
AB - BACKGROUND: Anaphase promoting complex (APC) is the biggest Cullin-RING E3 ligase
and is very important in cell cycle control; many anti-cancer agents target this.
APC controls the onset of chromosome separation and mitotic exit through securin
and cyclin B degradation, respectively. Its APC3 subunit identifies the APC
activators-Cdh1 and Cdc20. MATERIALS AND METHODS: The structural model of the
APC3 subunit of APC was developed by means of computational techniques; the
binding of a natural inhibitory compound to APC3 was also investigated. RESULTS:
It was found that APC3 structure consists of numerous helices organized in anti
parallel and the overall model is superhelical of tetratrico-peptide repeat (TPR)
domains. Furthermore, binding pocket of the natural inhibitory compound as APC3
inhibitor was shown. CONCLUSION: The findings are beneficial to understand the
mechanism of the APC activation and design inhibitory compounds.
PMID- 28401075
TI - Repeated Remote Ischemic Conditioning Effect on Ankle-brachial Index in Diabetic
Patients - A Randomized Control Trial.
AB - BACKGROUND: Remote ischemic preconditioning (RIPC) is a phenomenon where a short
period of ischemia in one organ protects against further ischemia in the other
organs. We hypothesized that RIPC occurring in diabetic patients with ankle
brachial index (ABI) between 0.70 and 0.90 were included with peripheral arterial
disease, would make the better coronary flow resulted in the increasing ABI.
MATERIALS AND METHODS: This randomized clinical trial study was done in the
Afshar Cardiovascular Hospital in Yazd between 2013 and 2014. Sixty participants
were randomly divided into two groups (intervention and control groups). The
intervention group was undergoing RIPC, and the control group was tested without
RIPC. RIPC was stimulated by giving three cycles of 5 min of ischemia followed by
5 min of reperfusion of both upper arms using a blood pressure cuff inflated to
200 mm Hg (n = 30). This was compared with no RIPC group which consisted of
placing a deflated blood pressure cuff on the upper limbs (n = 30). RESULTS: The
mean of ABI level before intervention in the RIPC and control group group was
0.82 +/- 0.055 and 0.83 +/- 0.0603 (P = 0.347) respectively, with no significant
difference. It was 0.86 +/- 0.066 in the RIPC group compared the control 0.83 +/-
0.0603 (P = 0.046). So levels of ABI were greater after intervention in the RIPC
group. The mean of ABI level increase from 0.82 +/- 0.05 to 0.86 +/- 0.06 in RIPC
group (P = 0.008). So the intervention group showed a significant increase in
ABI. CONCLUSIONS: RIPC through using a simple, noninvasive technique, composing
three cycles of 5 min-ischemia of both upper arms, showing a significant increase
in ABI level in diabetic patients.
PMID- 28401076
TI - Presentation of Placental Site Trophoblastic Tumor with Amenorrhea.
AB - Placental site throphoblastic tumor (PSTT) is a rare manifestation of gestational
trophoblastic neoplasia that may complicate any type of pregnancy. The disease is
unique from other type, and is defined by slow growth, low human chorionic
gonadotropin (hCG) serum levels, the late-onset metastatic potential, and most
significantly, insensitivity to chemotherapy. We describe a case of a 31-year-old
woman with prolonged amenorrhea and slightly elevated serum beta hCG (betahCG)
level, referred for termination of abnormal pregnancy. During curettage, necrotic
tissue was removed and severs vaginal bleeding was controlled with medical
therapy. Histology examination showed neoplastic intermediate trophoblastic cells
with invasion to the vessel wall compatible with PSTT. After that, hysterectomy
was down and serum betahCG declined to undetectable level 2 weeks after surgery
and was followed for 2 years without complication.
PMID- 28401077
TI - Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid,
and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or
Relapsed Hodgkin's lymphoma.
AB - BACKGROUND: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of
patients. The treatment of choice for these patients is high-dose chemotherapy
(HDCT) and autologous stem cell transplantation (ASCT). Response to salvage
chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT.
However, its applicability is restricted mostly to patients responding to salvage
chemotherapy. Optimal salvage regimen for these patients is unclear. In this
study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin,
and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine
arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of
relapsed or refractory HD. MATERIALS AND METHODS: In this retrospective analysis,
114 patients with primary refractory or relapsed HD who received ICE or ESHAP
salvage regimen were included. RESULTS: Of 114 patients, 47 (41.2%) were females
and the median age was 31.5 years. Response could be evaluated in 114 patients.
Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%)
achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the
evaluable ICE group (n = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39%
and in the ESHAP group (n = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and
58.9% (for ORR, P = 0.04), respectively. CONCLUSION: In patients with relapsed or
refractory HD, treatment with ESHAP seems to have higher rates of response than
ICE regimen does.
PMID- 28401078
TI - Probiotics: A New Era of Biotherapy.
AB - Probiotics or health-beneficial bacteria have only recently been introduced in
dentistry after years of successful use in mainly gastrointestinal disorders. The
concept of bacteriotherapy was first introduced in the beginning of 20th century.
They are administered in different quantities that allow for colon colonization.
These products help in stimulating health promoting flora and also suppressing
the pathologic colonization and disease spread. The use of probiotic plays an
important aspect in dentistry too, ever since the oral infections occupied the
prime spot among the other infections affecting the humans. Probiotics strengthen
the immune system to combat allergies, stress, exposure to toxic substances, and
other diseases. This review is an attempt to discuss briefly the role of
probiotics in oral health.
PMID- 28401079
TI - Mutation in delta-Sg Gene in Familial Dilated Cardiomyopathy.
AB - BACKGROUND: Mutations in different genes including dystrophin-associated
glycoprotein complex caused familial dilated cardiomyopathy which is a
genetically heterogeneous disease. The delta-SG gene contains nine exons spanning
a 433-kb region of genomic DNA. It encodes a 35-kDa, singlepass, and type II
transmembrane glycoprotein. MATERIALS AND METHODS: In this study for the first
time in Iran we screened 6 patients of a large family that they had positive
family history of MI or sudden death by next generation sequencing method.
RESULTS: By employing NGS method we found missense mutation (p.R97Q) of delta-SG
gene in 2 of 6 patients. CONCLUSIONS: The missense mutation (p.R97Q) in familial
DCM patients is reported for the first time in Iranian patients with cardiac
disease. Although this mutation is already known in other populations in Iran, it
is not reported before.
PMID- 28401080
TI - Comparison of the Frequency of Y-short Tandem Repeats Markers between Sadat and
Non-Sadat Populations in Isfahan Province of Iran.
AB - BACKGROUND: Y chromosome is one of the two sex chromosomes and is male specific.
Due to limited genetic exchange, the main part of that is passed virtually
unchanged from one generation to next generation. The short tandem repeats (STRs)
are almost constant on chromosomes that make them as an appropriate factor for
use in population genetic studies. In this study, we used the STRs of Y
chromosome markers in Sadat families and comparison with other families was
investigated. MATERIALS AND METHODS: In this study, sampling was done from fifty
unrelated males of Sadat families and fifty unrelated males of non-Sadat
families. After the extraction of DNA from blood samples and primer design,
polymerase chain reaction (PCR) was performed for each primer pairs separately.
The PCR products were run on agarose gel that followed by running on
polyacrylamide gel for better resolution. In addition, some sequenced samples
were used as identified markers to determine the length of other alleles in
polyacrylamide gel. RESULTS: The survey of six STR in two case and control groups
was carried out, and analysis revealed that the frequency of some alleles is
different in case group compared to control group. Allele frequency of the
markers DYS392, DYS393, DYS19, DYS390, DYS388, and DYS437 on the Y chromosome in
Sadat families was quite different in comparison with other families.
CONCLUSIONS: The reason for these differences in allele frequencies of the Sadat
family in comparison with other families is having a common ancestor.
PMID- 28401081
TI - Zinc in Pancreatic Islet Biology, Insulin Sensitivity, and Diabetes.
AB - About 20 chemical elements are nutritionally essential for humans with defined
molecular functions. Several essential and nonessential biometals are either
functional nutrients with antidiabetic actions or can be diabetogenic. A key
question remains whether changes in the metabolism of biometals and biominerals
are a consequence of diabetes or are involved in its etiology. Exploration of the
roles of zinc (Zn) in this regard is most revealing because 80 years of
scientific discoveries link zinc and diabetes. In pancreatic beta- and alpha
cells, zinc has specific functions in the biochemistry of insulin and glucagon.
When zinc ions are secreted during vesicular exocytosis, they have autocrine,
paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions
into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes
the majority of humans to developing diabetes. In target tissues, increased
availability of zinc enhances the insulin response by inhibiting protein tyrosine
phosphatase 1B, which controls the phosphorylation state of the insulin receptor
and hence downstream signalling. Inherited diseases of zinc metabolism,
environmental exposures that interfere with the control of cellular zinc
homeostasis, and nutritional or conditioned zinc deficiency influence the patho
biochemistry of diabetes. Accepting the view that zinc is one of the many factors
in multiple gene-environment interactions that cause the functional demise of
beta-cells generates an immense potential for treating and perhaps preventing
diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting
the control of cellular zinc in precision medicine are among the possible
interventions.
PMID- 28401082
TI - Vaccinium angustifolium Root Extract Suppresses FcERI Expression in Human
Basophilic KU812F Cells.
AB - Vaccinium angustifolium, commonly known as the lowbush blueberry, is a rich
source of flavonoids, with which various human physiological activities have been
associated. The present study focuses on the investigation of the effect of the
methanolic extract of V. angustifolium root extract (VAE) on high affinity
immunoglobulin E receptor (FcERI) alpha chain antibody (CRA-1)-induced allergic
reaction in human basophilic KU812F cells. The total phenolic content of VAE was
found to be 170+/-1.9 mg gallic acid equivalents/g. Flow cytometry analysis
revealed that the cell surface expression of FcERI was suppressed in a
concentration-dependent manner upon culture with VAE. Reverse-transcriptase
polymerase chain reaction analysis showed that the mRNA level of the FcERI alpha
chain was reduced in a concentration-dependent manner as a result of VAE
treatment. Western blot analysis revealed that the protein expression of FcERI
and the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 were
concentration-dependently inhibited by VAE. We determined that VAE inhibited anti
CRA-1-induced histamine release, in addition to the elevation of intracellular
calcium concentration ([Ca2+]i), in a concentration-dependent manner. These
results indicate that VAE may exert an anti-allergic effect via the inhibition of
calcium influx and histamine release, which occurs as a result of the down
regulation of FcERI expression through inhibition of ERK 1/2 activation.
PMID- 28401083
TI - Antioxidant Activities of Functional Beverage Concentrates Containing Herbal
Medicine Extracts.
AB - This study investigated the antioxidant activity of functional beverage
concentrates containing herbal medicine extracts (FBCH) using various antioxidant
assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity,
2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging
activity, and reducing power assay. The total polyphenolic content of FBCH (81.45
mg/100 g) was higher than Ssanghwa tea (SHT, 37.56 mg/100 g). The antioxidant
activities of FBCH showed 52.92% DPPH and 55.18% ABTS radical scavenging
activities at 100 mg/mL, respectively. FBCH showed significantly higher
antioxidant activities compared to the SHT (DPPH, 23.43%; ABTS, 22.21%; reducing
power optical density; 0.23, P<0.05). In addition, intracellular reactive oxygen
species generation significantly decreased in a concentration-dependent manner
following FBCH treatment. These results suggest that the addition of herbal
medicine extract contributes to the improved functionality of beverage
concentrates.
PMID- 28401084
TI - Influence of Roasting Treatment on the Antioxidant Activities and Color of
Burdock Root Tea.
AB - The major trend in the antioxidant market is the growing consumer demand for
natural antioxidants. Tea, one of the most widely consumed beverages in the
world, is an easy way to obtain antioxidant components from a natural source. Our
objective was to develop burdock root tea (BRT) with potent antioxidant activity
and good color quality. In order to obtain maximum antioxidant activity and
quality, the effect of roasting was determined. The antioxidant capacities and
total phenolic contents of BRT increased as roasting increased. The color of BRT
became darker with increased roasting, extraction time, and amount of burdock
roots. Color of BRT was also positively correlated with total antioxidant
capacity. Roasting significantly enhanced the total antioxidant activities and
color quality of BRT. These results suggest that roasting BRT increases
beneficial antioxidant components from burdock roots.
PMID- 28401085
TI - Physicochemical Qualities and Flavor Patterns of Traditional Chinese Vinegars
Manufactured by Different Fermentation Methods and Aging Periods.
AB - Physicochemical properties of Fujian Yongchun aged vinegar (FYAV) and Shanxi
mature vinegar (SMV) were compared in terms of the fermentation methods applied
and aging periods (3, 5, 8, and 10 years), and combined E-nose/E-tongue analyses
were performed to assess their flavors. Compared with submerged fermentation
derived FYAV, solid-state fermentation-derived SMV showed higher values of pH,
brix, soluble solids, total phenolic content, and antioxidant activity, but not
total acidity or total organic acids. Aging period resulted in an increase in pH,
total phenolic content, and antioxidant activity. Principal component analysis
based on E-tongue/E-nose analyses was performed to distinguish between the
vinegars produced by different fermentation methods and under aging periods.
Solid-state fermentation and an aging process were considered good techniques for
vinegar brewing, considering the various organic acids and high levels of total
phenolics and antioxidant activity.
PMID- 28401086
TI - Optimization of Maillard Reaction in Model System of Glucosamine and Cysteine
Using Response Surface Methodology.
AB - Sulfur-containing amino acids play important roles in good flavor generation in
Maillard reaction of non-enzymatic browning, so aqueous model systems of
glucosamine and cysteine were studied to investigate the effects of reaction
temperature, initial pH, reaction time, and concentration ratio of glucosamine
and cysteine. Response surface methodology was applied to optimize the
independent reaction parameters of cysteine and glucosamine in Maillard reaction.
Box-Behnken factorial design was used with 30 runs of 16 factorial levels, 8
axial levels and 6 central levels. The degree of Maillard reaction was determined
by reading absorption at 425 nm in a spectrophotometer and Hunter's L, a, and b
values. DeltaE was consequently set as the fifth response factor. In the
statistical analyses, determination coefficients (R2) for their absorbance,
Hunter's L, a, b values, and DeltaE were 0.94, 0.79, 0.73, 0.96, and 0.79,
respectively, showing that the absorbance and Hunter's b value were good
dependent variables for this model system. The optimum processing parameters were
determined to yield glucosamine-cysteine Maillard reaction product with higher
absorbance and higher colour change. The optimum estimated absorbance was
achieved at the condition of initial pH 8.0, 111 degrees C reaction temperature,
2.47 h reaction time, and 1.30 concentration ratio. The optimum condition for
colour change measured by Hunter's b value was 2.41 h reaction time, 114 degrees
C reaction temperature, initial pH 8.3, and 1.26 concentration ratio. These
results can provide the basic information for Maillard reaction of aqueous model
system between glucosamine and cysteine.
PMID- 28401087
TI - Low Dose Yeast Hydrolysate in Treatment of Obesity and Weight Loss.
AB - The anti-obesity effects of yeast hydrolysate (YH) supplementation (1.0 g/d) have
already been demonstrated. We investigated whether a low dose of YH (0.5 g/d, YH
500) also has the anti-obesity effects. Thirty obese women were randomly assigned
to the control or YH-500 groups. After 8 weeks, weight and body mass index were
significantly reduced by the YH treatment (0.5 g/d) (P<0.05). The YH-500 group
lost a significant amount of body fat after the 8-week treatment: fat mass 25.9
kg (baseline) versus 23.8 kg (8th week), P<0.01; fat mass ratio 38.8% (baseline)
versus 36.5% (8th week), P<0.05. The YH-500 group showed a significant reduction
in calorie intake during the 8-week treatment (P<0.001). The control group wanted
to eat much more food (P<0.05) and sometimes thought about eating more often
compared with the YH-500 group (P<0.05). Whereas the control group showed a
slightly increased sweet preference, the YH-500 group showed a significant
reduction in sweet preference (P<0.05). In conclusion, low dose YH
supplementation (0.5 g/d) may induce a reductions in weight and body fat in obese
women via the reduction of calorie intake.
PMID- 28401088
TI - Leaves of Raphanus sativus L. Shows Anti-Inflammatory Activity in LPS-Stimulated
Macrophages via Suppression of COX-2 and iNOS Expression.
AB - Raphanus sativus L. (RS) is a cruciferous vegetable that is widely consumed in
Korea. The anticancer activity of leaves of RS (RSL) extract has been
investigated; however, no studies focused on its anti-inflammatory effects.
Therefore, the aim of the current study was to evaluate the anti-inflammatory
effects of RSL extract. In brief, RSL powder was fractionated into n-hexane,
chloroform, ethyl acetate, n-butanol, and water-soluble fractions.
Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with each
fraction for initial screening. It was found that the chloroform fraction
significantly inhibited nitric oxide release in LPS-stimulated RAW264.7 cells
with a half maximal inhibitory concentration value of 196 MUg/mL. In addition,
the mRNA and protein expression levels of inducible nitric oxide synthase,
measured using reverse transcriptase-polymerase chain reaction and western
blotting, respectively, were reduced in a concentration-dependent manner.
Moreover, the inflammatory cyclooxygenase-2 enzyme expression decreased.
Furthermore, the expression of nuclear factor-kappa B (NF-kappaB), the key
regulator of the transcriptional activation of the inflammatory cytokine genes,
was reduced by the RSL chloroform fraction. Therefore, the results of our study
suggest that RSL exhibits anti-inflammatory effects in LPS-stimulated macrophages
via NF-kappaB inactivation.
PMID- 28401089
TI - Rheological Differences of Waxy Barley Flour Dispersions Mixed with Various Gums.
AB - Rheological properties of waxy barley flour (WBF) dispersions mixed with various
gums (carboxyl methyl celluleose, guar gum, gum arabic, konjac gum, locust bean
gum, tara gum, and xanthan gum) at different gum concentrations were examined in
steady and dynamic shear. WBF-gum mixture samples showed a clear trend of shear
thinning behavior and had a non-Newtonian nature with yield stress. Rheological
tests indicated that the flow and dynamic rheological parameter (apparent
viscosity, consistency index, yield stress, storage modulus, and loss modulus)
values of WBF dispersions mixed with gums, except for gum arabic, were
significantly higher than those of WBF with no gum, and also increased with an
increase in gum concentration. In particular, konjac gum at 0.6% among other gums
showed the highest rheological parameter values. Tan delta values of WBF-xanthan
gum mixtures were lower than those of other gums, showing that there is a more
pronounced synergistic effect on the elastic properties of WBF in the presence of
xanthan gum. Such synergistic effect was hypothesized by considering
thermodynamic compatibility between xanthan gum and WBF. These rheological
results suggest that in the WBF-gum mixture systems, the addition of gums
modified the flow and viscoelastic properties of WBF, and that these
modifications were dependent on the type of gum and gum concentration.
PMID- 28401090
TI - Non-Newtonian Characteristics of Gochujang and Chogochujang at Different
Temperatures.
AB - This study was conducted to determine the rheological properties of gochujang and
chogochujang at different temperatures (25, 35, and 45 degrees C). Rheological
properties of the samples were determined using a rotational rheometer at a shear
range of 1 to 40 s-1. Gochujang and chogochujang were found to be non-Newtonian
fluids according to the Herschel-Bulkley model. Yield stress and consistency
coefficient of gochujang at different temperatures were higher than those of
chogochujang, whereas the opposite was observed for flow behavior index.
Moreover, all rheological properties of gochujang and chogochujang decreased with
increasing temperature. The consistency coefficient was related to temperature
using an Arrhenius-type relationship. Gochujang (14.48 kJ/mol) had slightly
higher activation energy than chogochujang (14.03 kJ/mol).
PMID- 28401091
TI - Alternative approaches to preserve MSC progenitor potency.
PMID- 28401092
TI - The Consortium for Improving Survival of Lymphoma (CISL): recent achievements and
future perspective.
PMID- 28401093
TI - Lymphoglandular bodies in bone marrow aspirate smears.
PMID- 28401094
TI - Refractory anemia with ring sideroblasts and thrombocytosis.
PMID- 28401095
TI - A neutrophil phagocytosing bacteria.
PMID- 28401098
TI - Elevated expression of DNMT1 is associated with increased expansion and
proliferation of hematopoietic stem cells co-cultured with human MSCs.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) play an important role in hematopoietic
stem cell (HSC) maintenance, proliferation, and apoptosis. DNA methyltransferase
1 (DNMT1) is considered an essential factor in the maintenance of HSCs in
mammalian cells. Therefore, this study was conducted to evaluate the mRNA
expression level of DNMT1 during cord blood (CB)-HSC ex vivo expansion with MSCs.
METHODS: Ex vivo cultures of CB-HSCs were performed in three culture conditions
for 7 days: cytokines, cytokines with MSCs, and only MSCs. Total and viable cell
numbers were counted after 5 and 7 days using trypan blue stain, and the stem
cell percentage was then evaluated by flow cytometry. Moreover, in vitro colony
forming unit assay was carried out to detect clonogenic potential of HSCs at days
0 and 7 using MethoCult H4434. Finally, DNMT1 mRNA expression level was evaluated
by real-time polymerase chain reaction. RESULTS: Maximum CB-CD34+ cell expansion
was observed on day 7 in all the three cultures. After 7 days, ex vivo expansion
of CB-CD34+ cells indicated a significant decrease in DNMT1 expression in the
cytokine cultures, whereas in the two co-culture conditions DNMT1 expression was
increased. A significant difference between the number of CD34+ and CD34- cells
in the cytokine co-culture system was observed. CONCLUSION: These data indicated
that an elevated expression of DNMT1 is associated with increased expansion and
proliferation of HSCs co-cultured with human MSCs. Hence, DNMT1 may be a
potential factor in the maintenance of expanded HSCs co-cultured with human MSCs.
PMID- 28401096
TI - Regulation of the embryonic erythropoietic niche: a future perspective.
AB - The production of red blood cells, termed erythropoiesis, occurs in two waves in
the developing mouse embryo: first primitive erythropoiesis followed by
definitive erythropoiesis. In the mouse embryo, both primitive and definitive
erythropoiesis originates in the extra-embryonic yolk sac. The definitive wave
then migrates to the fetal liver, fetal spleen and fetal bone marrow as these
organs form. The fetal liver serves as the major organ for hematopoietic cell
expansion and erythroid maturation after mid-gestation. The erythropoietic niche,
which expresses critical cytokines such as stem cell factor (SCF), thrombopoietin
(TPO) and the insulin-like growth factors IGF1 and IGF2, supports hematopoietic
expansion in the fetal liver. Previously, our group demonstrated that DLK1+
hepatoblasts support fetal liver hematopoiesis through erythropoietin and SCF
release as well as extracellular matrix deposition. Loss of DLK1+ hepatoblasts in
Map2k4-/- mouse embryos resulted in decreased numbers of hematopoietic cells in
fetal liver. Genes encoding proteinases and peptidases were found to be highly
expressed in DLK1+ hepatoblasts. Capitalizing on this knowledge, and working on
the assumption that these proteinases and peptidases are generating small,
potentially biologically active peptides, we assessed a range of peptides for
their ability to support erythropoiesis in vitro. We identified KS-13
(PCT/JP2010/067011) as an erythropoietic peptide-a peptide which enhances the
production of red blood cells from progenitor cells. Here, we discuss the
elements regulating embryonic erythropoiesis with special attention to niche
cells, and demonstrate how this knowledge can be applied in the identification of
niche-derived peptides with potential therapeutic capability.
PMID- 28401097
TI - Enhanced differentiation of mesenchymal stromal cells by three-dimensional
culture and azacitidine.
AB - BACKGROUND: Mesenchymal stromal cells (MSCs) are useful for cell therapy because
of their potential for multilineage differentiation. However, MSCs that are
expanded in traditional two-dimensional (2D) culture systems eventually lose
their differentiation abilities. Therefore, we investigated whether azacitidine
(AZA) supplementation and three-dimensional culture (3D) could improve the
differentiation properties of MSCs. METHODS: 2D- or 3D-cultured MSCs which were
prepared according to the conventional or hanging-drop culture method
respectively, were treated with or without AZA (1 uM for 72 h), and their
osteogenic and adipogenic differentiation potential were determined and compared.
RESULTS: AZA treatment did not affect the cell apoptosis or viability in both 2D-
and 3D-cultured MSCs. However, compared to conventionally cultured 2D-MSCs, AZA
treated 2D-MSCs showed marginally increased differentiation abilities. In
contrast, 3D-MSCs showed significantly increased osteogenic and adipogenic
differentiation ability. When 3D culture was performed in the presence of AZA,
the osteogenic differentiation ability was further increased, whereas adipogenic
differentiation was not affected. CONCLUSION: 3D culture efficiently promoted the
multilineage differentiation of MSCs, and in combination with AZA, it could help
MSCs to acquire greater osteogenic differentiation ability. This optimized
culture method can enhance the therapeutic potential of MSCs.
PMID- 28401099
TI - Physicians' preferences and perceptions regarding donor selection in allogeneic
stem cell transplantation in Korea when a matched domestic donor is not
available.
AB - BACKGROUND: A number of alternative donor options exist for patients who fail to
find domestic HLA-matched donors for allogeneic hematopoietic stem cell
transplantation (allo-HSCT). We assessed physicians' perspectives on allo-HSCT
donor selection when a matched domestic donor is not available. METHODS: We
administered a questionnaire survey to 55 hematologists (response rate: 28%) who
attended the annual spring conference of the Korean Society of Haematology in
2015. The questionnaire contained four clinical allo-HSCT scenarios and the
respondents were asked to choose the most preferred donor among the given
options. RESULTS: In all four scenarios, the hematologists preferred a matched
international donor over partially mismatched unrelated domestic or haplo-matched
family donors. The numbers of hematologists who chose a matched international
donor (HLA 8/8) in cases of acute myeloid leukemia, chronic myeloid leukemia,
acute lymphoblastic leukemia, and aplastic anemia were 37 (67.3%), 41 (74.6%), 33
(60.0%), and 36 (65.5%), respectively. The important factors that affected donor
selection included "expecting better clinical outcomes (40.5%)" and "lower risk
of side effects (23.4%)." The majority of participants (80%) responded that allo
HSCT guidelines for donor selection customized for the Korean setting are
necessary. CONCLUSION: Although hematologists still prefer perfectly matched
foreign donors when a fully matched domestic allo-HSCT donor is not available, we
confirmed that there was variation in their responses. For evidence-based
clinical practice, it is necessary to provide further comparative clinical
evidence on allo-HSCT from haplo-matched family donors and fully matched
unrelated international donors.
PMID- 28401100
TI - Generation of hematopoietic stem cells from human embryonic stem cells using a
defined, stepwise, serum-free, and serum replacement-free monolayer culture
method.
AB - BACKGROUND: Embryonic stem cells (ESCs) can be expanded infinitely in vitro and
have the potential to differentiate into hematopoietic stem cells (HSCs); thus,
they are considered a useful source of cells for HSC production. Although several
technical in vitro methods for engineering HSCs from pluripotent stem cells have
been developed, clinical application of HSCs engineered from pluripotent stem
cells is restricted because of the possibility of xenogeneic contamination
resulting from the use of murine materials. METHODS: Human ESCs (CHA-hES15) were
cultured on growth factor-reduced Matrigel-coated dishes in the mTeSR1 serum-free
medium. When the cells were 70% confluent, we initiated HSC differentiation by
three methods involving (1) knockout serum replacement (KSR), cytokines, TGFb1,
EPO, and FLT3L; (2) KSR, cytokines, and bFGF; or (3) cytokines and bFGF. RESULTS:
Among the three differentiation methods, the minimal number of cytokines without
KSR resulted in the greatest production of HSCs. The optimized method resulted in
a higher proportion of CD34+CD43+ hematopoietic progenitor cells (HPCs) and
CD34+CD45+ HPCs compared to the other methods. In addition, the HSCs showed the
potential to differentiate into multiple lineages of hematopoietic cells in
vitro. CONCLUSION: In this study, we optimized a two-step, serum-free, animal
protein-free, KSR-free, feeder-free, chemically defined monolayer culture method
for generation of HSCs and hematopoietic stem and progenitor cells (HSPCs) from
human ESCs.
PMID- 28401101
TI - Warm autoimmune hemolytic anemia: experience from a single referral center in
Mexico City.
AB - BACKGROUND: Autoimmune hemolytic anemia (AIHA) is characterized by an autoimmune
mediated destruction of red blood cells. Warm AIHA (wAIHA) represents 60% of AIHA
cases and is associated with the positive detection of IgG and C3d in the direct
antiglobulin test (DAT). This study aimed to assess the clinical and laboratorial
differences between primary and secondary wAIHA patients from a referral center
in Mexico City. METHODS: All patients diagnosed with wAIHA in our institution
from January 1992 to December 2015 were included and received corticosteroids as
the first-line treatment. We analyzed the response to the first-line treatment,
relapse-free survival, and time to splenectomy. RESULTS: Eighty-nine patients
were included. Secondary wAIHA represented 55.1% of the cases. At diagnosis,
secondary wAIHA patients showed a DAT mixed pattern more frequently than primary
wAIHA patients (36.7 vs. 17.5%, P<0.001). In the survival analysis, patients with
secondary wAIHA had a lower time to response (18 vs. 37 days, P=0.05), median
disease-free survival (28.51 vs. 50.95 weeks, P=0.018), and time to splenectomy
(43.5 vs. 61 wks, P=0.029) than those with primary wAIHA. Due to economic
constraints, rituximab was considered as the third-line treatment in only two
patients. CONCLUSION: Secondary wAIHA may benefit from a longer low-dose steroid
maintenance period mainly due to its shorter time to relapse and time to
splenectomy than primary wAIHA.
PMID- 28401102
TI - Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran.
AB - BACKGROUND: Due to the tropism of human parvovirus B19 to erythroid progenitor
cells, infection in patients with an underlying hemolytic disorder such as beta
thalassemia major leads to suppression of erythrocyte formation, referred to as
transient aplasia crisis (TAC), which may be life-threatening. We investigated
the prevalence of parvovirus B19 among patients with beta thalassemia major
attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. METHODS: This cross
sectional study was performed to determine the presence of parvovirus B19 DNA in
blood samples and parvovirus B19 genotypes in plasma samples of patients with
thalassemia major. The population consisted of 150 patients with beta-thalassemia
major who attended the Zafar clinic in Tehran. Specimens were studied using a
real-time polymerase chain reaction assay. RESULTS: The prevalence of parvovirus
B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%)
were positive for B19 DNA. There was no significant correlation between blood
transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of
human parvovirus B19 revealed genotype I in these six patients. CONCLUSION: In
this study, acute B19 infections were detected in patients with beta thalassemia
major. Screening of such high-risk groups can considerably reduce the incidence
and prevalence of B19 infection; thus, screening is required for epidemiologic
surveillance and disease-prevention measures.
PMID- 28401103
TI - Characterization of clonal immunoglobulin heavy (IGH) V-D-J gene rearrangements
and the complementarity-determining region in South Indian patients with
precursor B-cell acute lymphoblastic leukemia.
AB - BACKGROUND: This study characterized clonal IG heavy V-D-J (IGH) gene
rearrangements in South Indian patients with precursor B-cell acute lymphoblastic
leukemia (precursor B-ALL) and identified age-related predominance in VDJ
rearrangements. METHODS: IGH rearrangements were studied in 50 precursor B-ALL
cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction
(PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement
sequences were analyzed using the IMGT/V-QUEST tool. RESULTS: Clonal IGH
rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1
IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes,
IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the
IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones,
respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame
whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic
mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average,
Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively.
CONCLUSION: The IGHV3 gene was frequently used whereas lower frequencies of IGHV5
and IGHV6 and a higher frequency of IGHV4 were detected in children compared with
young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene
was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements
in precursor-B-ALL did not show any significant age-associated genotype pattern
attributed to our population.
PMID- 28401104
TI - Therapy-related acute promyelocytic leukemia in plasma cell myeloma treated with
melphalan: a case report and literature review.
PMID- 28401105
TI - Hypercalcemia, multiple osteolytic lesions, and acute renal failure: a rare
presentation of B-cell acute lymphoblastic leukemia.
PMID- 28401106
TI - JAK2 exon 12 mutation-positive myeloproliferative neoplasm associated with
recurrent thromboembolism.
PMID- 28401107
TI - Is N-acetylcysteine infusion an effective treatment option in L-asparaginase
associated hepatotoxicity?
PMID- 28401108
TI - A case of lymphocytic variant hypereosinophilic syndrome with sub-diagnostic
systemic mastocytosis.
PMID- 28401109
TI - A rare case of erythrophagocytosis by neutrophils on the peripheral blood smear.
PMID- 28401110
TI - The first case report of a patient with coexisting hemophilia B and Down
syndrome.
PMID- 28401111
TI - Added sugar in the packaged foods and beverages available at a major Canadian
retailer in 2015: a descriptive analysis.
AB - BACKGROUND: Excess consumption of added sugars has been associated with a variety
of health problems, but there is little information available characterizing
added sugar in the Canadian food supply. This study examined the presence and
types of added sugars in the packaged food and beverage products available at a
major Canadian grocery retailer. METHODS: We searched the ingredients lists of
over 40 000 packaged food products available for sale in March 2015 for a variety
of added sugar terms. Proportions of food products containing added sugar were
identified overall and within food product categories. Differences in total sugar
content were identified between food products with and without added sugar.
RESULTS: Overall, 66% of the packaged food products analyzed contained at least 1
added sugar. The added sugar term "sugar" (and its variations) appeared the most
frequently, followed by "dextrose." Added sugar presence and total sugar content
varied within many product categories but were consistently higher in expected
categories such as "beverages." Mean total sugar content was significantly higher
in products with added sugar than in those without, both overall (p < 0.001) and
within most product subcategories (p < 0.02). INTERPRETATION: About two-thirds of
the packaged foods and beverages available at a major Canadian grocery retailer
contain added sugar, similar to recent patterns estimated for the US food supply.
The results provide an estimation of the baseline characterization of added sugar
in the Canadian food supply, which can be used to assess outcomes of future
changes to sugar labelling policies in Canada.
PMID- 28401112
TI - Cancer incidence attributable to insufficient fibre consumption in Alberta in
2012.
AB - BACKGROUND: Insufficient fibre consumption has been associated with a increased
risk of colorectal cancer. The purpose of this study was to estimate the
proportion and absolute number of cancers in Alberta that could be attributed to
insufficient fibre consumption in 2012. METHODS: The number and proportion of
colorectal cancers in Alberta attributable to insufficient fibre consumption were
estimated using the population attributable risk. Relative risks were obtained
from the World Cancer Research Fund's 2011 Continuous Update Project on
colorectal cancer, and the prevalence of insufficient fibre consumption (< 23
g/d) was estimated using dietary data from Alberta's Tomorrow Project. Age- and
sex-specific colorectal cancer incidence data for 2012 were obtained from the
Alberta Cancer Registry. RESULTS: Between 66% and 67% of men and between 73% and
78% of women reported a diet with insufficient fibre consumption. Population
attributable risk estimates for colorectal cancer were marginally higher in men,
ranging from 6.3% to 6.8% across age groups, whereas in women they ranged from
5.0% to 5.5%. Overall, 6.0% of colorectal cancers or 0.7% of all cancers in
Alberta in 2012 were estimated to be attributable to insufficient fibre
consumption. INTERPRETATION: Insufficient fibre consumption accounted for 6.0% of
colorectal cancers in Alberta in 2012. Increasing fibre consumption in Alberta
has the potential to reduce to the future burden of colorectal cancer in the
province.
PMID- 28401113
TI - Canadian Institutes of Health Research funding of prison health research: a
descriptive study.
AB - BACKGROUND: Health research provides a means to define health status and to
identify ways to improve health. Our objective was to define the proportion of
grants and funding from the Government of Canada's health research investment
agency, the Canadian Institutes of Health Research (CIHR), that was awarded for
prison health research, and to describe the characteristics of funded grants.
METHODS: In this descriptive study, we defined prison health research as research
on the health and health care of people in prisons and at the time of their
release. We searched the CIHR Funding Decisions Database by subject and by
investigator name for funded grants for prison health research in Canada in all
competitions between 2010 and 2014. We calculated the proportion of grants and
funding awarded for prison health research, and described the characteristics of
funded grants. RESULTS: During the 5-year study period, 21 grants were awarded
that included a focus on prison health research, for a total of $2 289 948. Six
of these grants were operating grants and 6 supported graduate or fellowship
training. In total, 0.13% of all grants and 0.05% of all funding was for prison
health research. INTERPRETATION: A relatively small proportion of CIHR grants and
funding were awarded for prison health research between 2010 and 2014. If prison
health is a priority for Canada, strategic initiatives that include funding
opportunities could be developed to support prison health research in Canada.
PMID- 28401114
TI - Time trends in organ donation after neurologic determination of death: a cohort
study.
AB - BACKGROUND: The cause of brain injury may influence the number of organs that can
be procured and transplanted with donation following neurologic determination of
death. We investigated whether the distribution of causes responsible for
neurologic death has changed over time and, if so, whether this has had an impact
on organ quality, transplantation rates and recipient outcomes. METHODS: We
performed a cohort study involving consecutive brain-dead organ donors in
southern Alberta between 2003 and 2014. For each donor, we determined last
available measures of organ injury and number of organs transplanted, and
compared these variables for various causes of neurologic death. We compared
trends to national Canadian data for 2000-2013 (2000-2011 for Quebec). RESULTS:
There were 226 brain-dead organ donors over the study period, of whom 100 (44.2%)
had anoxic brain injury, 63 (27.9%) had stroke, and 51 (22.6%) had traumatic
brain injury. The relative proportion of donors with traumatic brain injury
decreased over time (> 30% in 2003-2005 v. 6%-23% in 2012-2014) (p = 0.004),
whereas that with anoxic brain injury increased (14%-37% v. 46%-80%,
respectively) (p < 0.001). Nationally, the annual number of brain-dead donors
with traumatic brain injury decreased from 4.4 to less than 3 per million
population between 2000 and 2013, and that with anoxic brain injury increased
from 1.1 to 3.1 per million. Donors with anoxic brain injury had higher
concentrations of creatinine, alanine aminotransferase and troponin T, and lower
PaO2/FIO2 and urine output than donors with other diagnoses. The average number
of organs transplanted per donor was 3.6 with anoxic brain injury versus 4.5 with
traumatic brain injury or stroke (p = 0.002). INTERPRETATION: Anoxic brain injury
has become a leading cause of organ donation after neurologic determination of
death in Canada. Organs from donors with anoxic brain injury have a greater
degree of injury, and fewer are transplanted. These findings have implications
for availability of organs for transplantation in patients with end-stage organ
failure.
PMID- 28401115
TI - Team-based innovations in primary care delivery in Quebec and timely physician
follow-up after hospital discharge: a population-based cohort study.
AB - BACKGROUND: Outpatient follow-up has been a key intervention point in addressing
gaps in care after hospital discharge. We sought to estimate the association
between enrolment in new team-based primary care practices and 30-day
postdischarge physician follow-up among older patients and patients with chronic
illnesses who were admitted to hospital in Quebec, Canada. METHODS: Patients were
selected into this cohort if a primary care physician enrolled them as a
"vulnerable patient" between November 2002 and January 2005. Data for this
analysis included province-wide health insurance claims for inpatient and
outpatient services delivered between November 2002 and January 2009 in Quebec.
The primary analysis examined time to the first outpatient postdischarge follow
up service provided by either a primary care physician or a medical specialist.
We used marginal structural models to estimate adjusted rates of follow-up with a
primary care physician or with a medical specialist by primary care delivery
models. RESULTS: We extracted billing data for 312 377 patients that represented
620 656 index admissions for any cause from 2002 to 2009. Rates of 30-day follow
up were 374 visits to primary care physicians and 422 visits to medical
specialists per 1000 discharges. Rates of primary care physician follow-up were
similar across primary care delivery models, except for patients with very high
morbidity; these patients had significantly higher rates of follow-up with a
primary care physician if they were enrolled in team-based primary care practices
(30-d rate difference [RD] 13.3 more follow-up visits per 1000 discharges, 95%
confidence interval [CI] 6.8 to 19.8). Rates of follow-up with a medical
specialist were lower among patients enrolled in team-based practices,
particularly within 15 days of hospital discharge (15-d RD 25.1 fewer follow-up
visits per 1000 discharges, 95% CI 21.1 to 29.1). INTERPRETATION: Our study found
lower rates of postdischarge follow-up with a medical specialist among older
patients and patients with chronic illness who were enrolled in team-based
primary care practices compared with those enrolled in traditional primary care
practices. Future research is needed to better understand the role of primary
health care service organization in improving acute postdischarge care.
PMID- 28401116
TI - Implementation of an intervention to reduce population-based screening for
vitamin D deficiency: a cross-sectional study.
AB - BACKGROUND: We describe the implementation of an intervention in Alberta in
support of the Choosing Wisely Canada recommendation against population screening
for vitamin D deficiency (as determined by serum total 25-hydroxyvitamin D
testing). We hypothesized that the introduction of a specialized requisition for
vitamin D testing would reduce the annual number of vitamin D tests performed.
METHODS: We performed a cross-sectional observational study that included all
vitamin D tests ordered in Alberta between Apr. 1, 2015, and Mar. 31, 2016. There
were no exclusion criteria. A special requisition for ordering vitamin D tests in
Alberta was introduced on Apr. 1, 2015. Using an interrupted time series model,
we compared predicted versus observed vitamin D test volumes for the 12-month
period following the introduction of the new requisition. The sole outcome
measure was the monthly change in volume of vitamin D testing. In addition, we
calculated any cost savings as a result of reduced testing. RESULTS: Over the
first 12 months of the intervention, there was a reduction in the number of tests
ordered from a predicted 342 477 tests to 29 525 tests (91.4% reduction). This
decrease represented a direct spending decrease of Can$938 856-$1 564 760 per
year in Alberta. INTERPRETATION: A provincially led implementation of a Choosing
Wisely Canada recommendation resulted in a large and sustained reduction in serum
total 25-hydroxyvitamin D testing in Alberta. This study shows that provincially
led interventions based on Choosing Wisely Canada recommendations can result in
substantial reductions in laboratory tests.
PMID- 28401117
TI - Cost-related nonadherence to prescribed medicines among older Canadians in 2014:
a cross-sectional analysis of a telephone survey.
AB - BACKGROUND: Canadians receive universal coverage for medically necessary hospital
and physician services, but pharmaceutical coverage is incomplete. We sought to
assess the effects of cost on access to medicines among older Canadians using
data from a large survey conducted in 2014. METHODS: This is a cross-sectional
analysis of data from the Commonwealth Fund's 2014 International Health Policy
Survey of Older Adults. Our primary outcome variable was self-reported cost
related nonadherence in the form of either not filling a prescription or skipping
doses within the last 12 months because of out-of-pocket costs. We computed
sample-weighted estimates of the population prevalence of cost-related
nonadherence and conducted logistic regression analyses to determine associated
factors. RESULTS: We estimate that the prevalence of cost-related nonadherence in
2014 among Canadians aged 55 years and older was 8.3% (about 1 in 12). The
population prevalence and adjusted odds of cost-related nonadherence was
significantly higher among Canadians who were younger, in worse health, poorer or
without private health insurance. Regional differences in population prevalence
of cost-related nonadherence were not significant. The only provincial or
regional difference in the adjusted odds of cost-related nonadherence was that
residents of Quebec aged 55-64 years were about half as likely to report
nonadherence as similarly aged residents of Ontario, our reference province
(adjusted odds ratio 0.49, 95% confidence interval 0.29-0.82). INTERPRETATION:
The financial accessibility of prescription medicines still is a substantial
public health issue in Canada that affects 1 in 12 Canadians older than 55 years
of age. Older Canadians at greatest risk of cost-related nonadherence to
prescribed treatments are those with low incomes and those without private
insurance to cover costs not covered by public programs.
PMID- 28401118
TI - Frequency of and variation in low-value care in primary care: a retrospective
cohort study.
AB - BACKGROUND: Low-value care, defined as care with a lack of benefit, can lead to
higher health care costs, inconvenience to patients and, in some cases, harm to
patients. The objectives of this study are to conduct exploratory analyses to
understand how frequently selected low-value tests are ordered, to assess the
degree of variation in ordering that exists across regions and practices, and to
identify services that may warrant further investigation and targeted
interventions. METHODS: We conducted a population-based retrospective cohort
study using administrative health care databases from Ontario to identify rates
of use of the following low-value services between fiscal years 2008/09 and
2012/13: computed tomography (CT) or magnetic resonance imaging (MRI) after a
diagnosis of low back pain, Papanicolaou testing in women less than 21 years of
age or older than 69 years of age and repeated dual-energy X-ray absorptiometry
(DEXA) scanning within 2 years of an index scan. Regional and practice-level
rates were calculated. Bivariate analyses were conducted to explore associations
between patient factors and repeat DEXA scans. RESULTS: Repeated DEXA scans were
the most common service (21.0%), whereas cervical cancer screening among women
less than 21 years of age or older than 69 years of age (8.0%) and CT or MRI
imaging for low back pain (4.5%) were less common. There was substantial
variation across practices with rates of repeated DEXA scans, ranging from 4.0%
to 54.9%, and cervical cancer screening, ranging from 0.9% to 35.2%. Patients
with a high-risk index DEXA were more likely to receive a repeat scan (28.1%)
than those with a baseline (8.9%) or low-risk (8.1%) scan. INTERPRETATION: There
is significant, practice-level variation in the frequency of low-value testing
for DEXA scans, back imaging and cervical cancer screening. There is a particular
need for interventions that aim to reduce unnecessary DEXA scans.
PMID- 28401119
TI - Long-term sedative use among community-dwelling adults: a population-based
analysis.
AB - BACKGROUND: Chronic use of benzodiazepines and benzodiazepine-like sedatives (z
drugs) presents substantial risks to people of all ages. We sought to assess
trends in long-term sedative use among community-dwelling adults in British
Columbia. METHODS: Using population-based linked administrative databases, we
examined longitudinal trends in age-standardized rates of sedative use among
different age groups of community-dwelling adults (age >= 18 yr), from 2004 to
2013. For each calendar year, we classified adults as nonusers, short-term users,
or long-term users of sedatives based on their patterns of sedative dispensation.
For calendar year 2013, we applied cross-sectional analysis and estimated
logistic regression models to identify health and socioeconomic risk factors
associated with long-term sedative use. RESULTS: More than half (53.4%) of long
term users of sedatives in British Columbia are between ages 18 and 64 years
(young and middle-aged adults). From 2004 to 2013, long-term sedative use
remained stable among adults more than 65 years of age (older adults) and
increased slightly among young and middle-aged adults. Although the use of
benzodiazepines decreased during the study period, the trend was offset by equal
or greater increases in long-term use of z-drugs. Being an older adult, sick,
poor and single were associated with increased odds of long-term sedative use.
INTERPRETATION: Despite efforts to stem such patterns of medication use, long
term use of sedatives increased in British Columbia between 2004 and 2013. This
increase was driven largely by increased use among middle-aged adults. Future
deprescribing efforts that target adults of all ages may help curb this trend.
PMID- 28401120
TI - Estimating patient-borne water and electricity costs in home hemodialysis: a
simulation.
AB - BACKGROUND: Home hemodialysis is associated with lower costs to the health care
system compared with conventional facility-based hemodialysis because of lower
staffing and overhead costs, and by transferring the treatment cost of utilities
(water and power) to the patient. The purpose of this study was to determine the
utility costs of home hemodialysis and create a formula such that patients and
renal programs can estimate the annual patient-borne costs involved with this
type of treatment. METHODS: Seven common combinations of treatment duration and
dialysate flows were replicated 5 times using various combinations of home
hemodialysis and reverse osmosis machines. Real-time utility (electricity and
water) consumption was monitored during these simulations. A generic formula was
developed to allow patients and programs to calculate a more precise estimate of
utility costs based on individual combinations of dialysis intensity, frequency
and utility costs unique to any patient. RESULTS: Using typical 2014 utility
costs for Edmonton, the most expensive prescription was for nocturnal home
hemodialysis (8 h at 300 mL/min, 6 d/wk), which resulted in a utility cost of
$1269 per year; the least expensive prescription was for conventional home
hemodialysis (4 h at 500 mL/min, 3 d/wk), which cost $420 per year. Water
consumption makes up most of this expense, with electricity accounting for only
12% of the cost. INTERPRETATION: We show that a substantial cost burden is
transferred to the patient on home hemodialysis, which would otherwise be borne
by the renal program.
PMID- 28401121
TI - Sex and gender considerations in Canadian clinical practice guidelines: a
systematic review.
AB - BACKGROUND: The importance of sex and gender in the diagnosis and management of
health conditions is well established, but the extent to which this evidence is
integrated into clinical practice guidelines remains unknown. We aimed to
determine the proportion of Canadian clinical practice guidelines that integrate
evidence on sex and gender considerations. METHODS: We searched the Canadian
Medical Association's CPG Infobase, PubMed, all provincial/territorial websites
and websites of professional organizations for English- and French-language
Canadian clinical practice guidelines published between January 2013 and June
2015 on selected conditions identified as priorities by policy-makers and
practitioners. Citations and text were searched electronically using keyword
terms related to sex and gender. Three investigators independently analyzed and
categorized the content of text-positive clinical practice guidelines based on
clinical relevance for practitioners. RESULTS: Of the 118 clinical practice
guidelines that met the inclusion criteria, 79 (66.9%) were text-positive for sex
and/or gender keywords; 8 (10%) of the 79 used the keywords only in relation to
pregnancy. Of the remaining 71 guidelines, 25 (35%) contained sex-related
diagnostic or management recommendations. An additional 5 (7%) contained
recommendations for sex-specific laboratory reference values, 29 (41%) referred
to differences in epidemiologic features or risk factors only, and 12 (17%)
contained nonrelevant mentions of search keywords. Twenty-five (35%) of the text
positive guidelines used the terms "sex" and/or "gender" correctly.
INTERPRETATION: Recommendations related to sex and gender are inconsistently
reported in Canadian clinical practice guidelines. Guidelines such as the Sex and
Gender Equity in Research guidelines may help inform the meaningful inclusion of
sex and gender evidence in the development of clinical practice guidelines.
PMID- 28401122
TI - Quality indicators for the detection and management of chronic kidney disease in
primary care in Canada derived from a modified Delphi panel approach.
AB - BACKGROUND: The detection and management of chronic kidney disease lies within
primary care; however, performance measures applicable in the Canadian context
are lacking. We sought to develop a set of primary care quality indicators for
chronic kidney disease in the Canadian setting and to assess the current state of
the disease's detection and management in primary care. METHODS: We used a
modified Delphi panel approach, involving 20 panel members from across Canada (10
family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1
pharmacist). Indicators identified from peer-reviewed and grey literature sources
were subjected to 3 rounds of voting to develop a set of quality indicators for
the detection and management of chronic kidney disease in the primary care
setting. The final indicators were applied to primary care electronic medical
records in the Electronic Medical Record Administrative data Linked Database
(EMRALD) to assess the current state of primary care detection and management of
chronic kidney disease in Ontario. RESULTS: Seventeen indicators made up the
final list, with 1 under the category Prevalence, Incidence and Mortality; 4
under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under
Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis,
6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of
patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were
female. Diagnosis and screening for chronic kidney disease were poorly performed.
Only 27.1% of patients with stage 3 or higher disease had their diagnosis
documented in their cumulative patient profile. Albumin-creatinine ratio testing
was only performed for 16.3% of patients with a low estimated glomerular
filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic
kidney disease. Family physicians performed relatively better with the management
of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease
having an eGFR performed in the previous 18 months and 83.1% having a blood
pressure recorded in the previous 9 months. INTERPRETATION: We propose a set of
measurable indicators to evaluate the quality of the management of chronic kidney
disease in primary care. These indicators may be used to identify opportunities
to improve current practice in Canada.
PMID- 28401123
TI - Setting an implementation research agenda for Canadian investments in global
maternal, newborn, child and adolescent health: a research prioritization
exercise.
AB - BACKGROUND: Improving global maternal, newborn, child and adolescent health
(MNCAH) is a top development priority in Canada, as shown by the $6.35 billion in
pledges toward the Muskoka Initiative since 2010. To guide Canadian research
investments, we aimed to systematically identify a set of implementation research
priorities for MNCAH in low- and middle-income countries. METHODS: We adapted the
Child Health and Nutrition Research Initiative method. We scanned the Child
Health and Nutrition Research Initiative literature and extracted research
questions pertaining to delivery of interventions, inviting Canadian experts on
MNCAH to generate additional questions. The experts scored a combined list of 97
questions against 5 criteria: answerability, feasibility, deliverability, impact
and effect on equity. These questions were ranked using a research priority
score, and the average expert agreement score was calculated for each question.
RESULTS: The overall research priority score ranged from 40.14 to 89.25, with a
median of 71.84. The average expert agreement scores ranged from 0.51 to 0.82,
with a median of 0.64. Highly-ranked research questions varied across the life
course and focused on improving detection and care-seeking for childhood
illnesses, overcoming barriers to intervention uptake and delivery, effectively
implementing human resources and mobile technology, and increasing coverage among
at-risk populations. Children were the most represented target population and
most questions pertained to interventions delivered at the household or community
level. INTERPRETATION: Investing in implementation research is critical to
achieving the Sustainable Development Goal of ensuring health and well-being for
all. The proposed research agenda is expected to drive action and Canadian
research investments to improve MNCAH.
PMID- 28401124
TI - Unintentional injuries in children and youth from immigrant families in Ontario,
Canada: a population-based cross-sectional study.
AB - BACKGROUND: Unintentional injury is the leading cause of childhood death. Injury
is associated with a number of sociodemographic characteristics, but little is
known about risk in immigrants. Our objective was to examine the association
between family immigrant status and unintentional injury in children and youth.
METHODS: We performed a population-based, cross-sectional study involving
children and youth (age 0-24 yr) residing in Ontario from 2008 to 2012. Multiple
linked health and administrative databases were used to describe unintentional
injuries by family immigrant status. Unintentional injury events (e.g., emergency
department visits, admissions to hospital, deaths) were analyzed using Poisson
regression models to estimate rate ratios (RRs) for injury by immigrant status.
RESULTS: Annualized injury rates were 11 749 emergency department visits per 100
000 population, 267 hospital admissions per 100 000 population and 12 deaths per
100 000 population. Injury rates were lower among immigrants across all causes of
unintentional injury (adjusted RR 0.56, 95% confidence interval [CI] 0.54-0.59).
Among nonimmigrants, lowest neighbourhood income quintile was associated with the
highest rates (RR 1.13, 95% CI 1.08-1.18, quintile 5 v. 1); among immigrants,
lowest income quintile was associated with the lowest rates of injury (RR 0.88,
95% CI 0.82-0.94, quintile 5 v. 1). Highest rates of injury for nonimmigrants
were among adolescents (age 10-14 yr, RR 1.23, 95% CI 1.18-1.28; v. 20-24 yr),
but for immigrants, was highest among young children (0-4 yr RR 1.23, 95% CI 1.16
1.31; v. 20-24 yr). INTERPRETATION: Rates of unintentional injury are lower among
immigrant than among Canadian-born children, supporting a healthy immigrant
effect. Socioeconomic status and age have different associations with injury
risk, suggesting alternative causal pathways for injuries in immigrant children
and youth.
PMID- 28401125
TI - Drug therapies for chronic hepatitis C infection: a cost-effectiveness analysis.
AB - BACKGROUND: Before 2011, pegylated interferon plus ribavirin was the standard
therapy for chronic hepatitis C. Interferon-free direct-acting antiviral agents
were then approved. Although these treatments appear to be more effective, they
are substantially more expensive. In anticipation of the need for information
regarding the comparative cost-effectiveness of new regimens in a recent
therapeutic review, we conducted the analysis to inform listing decision in
Canada. METHODS: A state-transition model was developed in the form of a cost
utility analysis. Regimens included in the analysis were comprehensive. The
cohort under consideration had a mean age of 50 years. The cohort was defined by
treatment status and cirrhosis status. Inputs for the model were derived from
published sources and validated by clinical experts. RESULTS: For each genotype 1
population, at least 1 of the interferon-free agents appeared to be economically
attractive compared with pegylated interferon-ribavirin, at a willingness-to-pay
of $50 000 per quality-adjusted life-year. The drug that was the most cost
effective varied by population. For genotype 2-4 population, the direct-acting
antiviral therapies appeared not to be economically attractive compared with
pegylated interferon-ribavirin for the treatment-naive; however, there were
direct-acting antiviral therapies that appeared to be attractive when compared
with no treatment for the treatment-experienced. INTERPRETATION: Public health
policy should be informed by consideration of health benefit, social and ethical
values, feasibility and cost-effectiveness. Our analysis assists the development
of reimbursements and policies for interferon-free direct-acting antiviral agent
regimens for chronic hepatitis C infection by informing the last criterion.
Considering the rapid development of treatments for chronic hepatitis C, further
update and expanded reviews will be necessary.
PMID- 28401126
TI - Factors associated with the duration of disability benefits claims among Canadian
workers: a retrospective cohort study.
AB - BACKGROUND: Disability insurance protects workers from total loss of income in
case of a disabling injury or illness by providing wage-replacement benefits. To
better inform early identification of claims at risk of prolonged recovery, we
explored predictors of the duration of disability benefits claims. METHODS: We
conducted a retrospective cohort study using claims data provided by SSQ Life
Insurance Company Inc., a private Canadian disability insurer. We examined all
claims SSQ approved for short- and long-term disability benefits from Jan. 1,
2007, to Mar. 31, 2014, and evaluated the association between 9 variables and
duration of short- and long-term disability benefits using Cox proportional
hazards regression analyses. RESULTS: For both short- (n = 70 776) and long-term
disability (n = 22 205) claims, and across all disorders, older age, female sex,
heavy job demands, presence of comorbidity, attending an independent medical
evaluation, receipt of rehabilitation therapy and longer time to claim approval
were associated with longer claim duration. Higher predisability salary was
associated with longer short-term disability claim duration. Quebec residency was
associated with longer short-term disability claim duration among workers with
psychological disorders, but shorter short-term disability claim duration among
those with musculoskeletal complaints and other illnesses. For long-term
disability claims, however, residing in Quebec was associated with shorter claim
duration, although the size of the association differed across clinical
conditions. INTERPRETATION: The factors we found to be associated with the
duration of short- and long-term disability claims may be helpful to identify
claims at risk of prolonged recovery. Our study has limitations, however, and
well-designed prospective studies are needed to confirm our findings and identify
other promising predictors.
PMID- 28401127
TI - Diagnostic and referral intervals for Manitoba women with epithelial ovarian
cancer - the Manitoba Ovarian Cancer Outcomes (MOCO) study group: a retrospective
cross-sectional study.
AB - BACKGROUND: Epithelial ovarian cancer has the highest mortality of all
gynecologic cancers. The poor survival rates are often attributed to the advanced
stage at which most of these cancers are detected. We sought to examine the
effects of patient demographics, comorbidities and presenting symptoms on
diagnostic and referral intervals by location of first presentation (emergency
department v. elsewhere) and to identify factors that affect these intervals.
METHODS: We performed a retrospective analysis of chart and medical record data
for ovarian cancers, with the exceptions of sex cord and germ cell tumours,
diagnosed between 2004 and 2010 in Manitoba, Canada. Data were collected on
baseline characteristics, time to diagnosis and referral, number and type of
physician visits and emergency department visits. RESULTS: The final cohort
consisted of 601 patients. Sixty-three percent of patients received their
diagnosis within 60 days of initial presentation, and 75.2% had their cancer
diagnosed within 2 physician encounters. The median diagnostic interval for all
stages of patients presenting to the emergency department was 7 days, compared
with 55 days for patients presenting elsewhere. Early stage patients not
presenting to the emergency department had their diagnosis a median of 34.0 days
later than patients with advanced disease (95% confidence interval [CI] 22.22 to
45.69, p < 0.0001). The presence of some symptoms was associated with shortened
diagnostic intervals. Patients with serous, clear-cell or endometrioid histotypes
were less likely to have first presentation beginning in the emergency department
(odds ratio [OR] 0.40, 95% CI 0.24 to 0.64, p = 0.0001; OR 0.28, 95% CI 0.14 to
0.59, p = 0.007) than those with unclassified epithelial histotype.
INTERPRETATION: For this group of patients, the main factor associated with
diagnostic and referral intervals is presentation to the emergency department.
These patients likely required more urgent attention for their more symptomatic
disease, leading to quicker diagnosis and referral patterns, despite poorer
prognosis.
PMID- 28401128
TI - Planning for retirement from medicine: a mixed-methods study.
AB - BACKGROUND: Evidence suggests there are important personal and social
consequences associated with inadequate retirement planning for physicians. We
evaluated whether academic physicians felt satisfied with their retirement
planning, and identified obstacles to retirement planning and a set of factors to
facilitate retirement planning. METHODS: We applied a sequential mixed-methods
research design to explore and examine factors that facilitate academic physician
retirement planning using data collected from multiple sources (including 7 focus
groups, an internet-based survey and 23 in-depth interviews). We examined survey
results regarding retirement planning satisfaction and preferences for complete
versus gradual retirement. We used thematic analysis to examine verbatim
transcripts and notes from the focus groups and interviews. RESULTS: Survey data
(response rate 51%) indicated that 10% of respondents were very satisfied with
their retirement planning and 89.5% would prefer to retire gradually rather than
stop work completely. Key barriers to retirement planning that emerged included
poor personal financial management, rigid institutional structures and
professional norms. Facilitators included financial planning resources for
physicians at multiple career stages, opportunities and resources for later
career transitions and later-career mentorship support for intergenerational
collaboration, and recognition of retirees. INTERPRETATION: Key findings
highlight perceived barriers to retirement planning at various career stages in
addition to factors that can enhance physicians' retirement planning, including
creating gradual and flexible retirement options, supporting ongoing discussions
about financial planning and later career transitions, and fostering a culture
that continues to honour and involve retirees. Medical institutions could foster
innovative models for later-career transitions from medicine in ways that address
physicians' needs at various career stages, support gradual transitions from
practice and recognize the value of experienced, capable later-career physicians
and retirees.
PMID- 28401129
TI - Circulating concentrations and relative percent composition of trans fatty acids
in healthy Canadian young adults between 2004 and 2010: a cross-sectional study.
AB - BACKGROUND: Trans fatty acids (TFAs) produced from industrial partial
hydrogenation of vegetable oils have been the subject of much research regarding
their negative effect on the development of chronic diseases, and recommendations
to label foods with partially hydrogenated vegetable oils and limit their levels
were introduced in Canada in 2003 and 2007, respectively. Our aim was to
determine temporal changes in circulating plasma TFAs in a population of young
healthy Canadian adults after the introduction of the guidelines. METHODS: In
this study, circulating plasma concentrations and relative percent composition of
individual TFAs over time (2004-2010) were determined in a cross-sectional cohort
of young healthy Canadian adults as part of the Toronto Nutrigenomics study.
RESULTS: A total of 1294 participants were included in the cohort. Relative to
2004, total TFA levels were significantly lower in 2005-2009 (p < 0.05), but not
in 2010. Although levels of 16:1t9 and 18:1t11 declined after 2004, levels of
18:1t9 and 18:1t10 were significantly lower in 2005-2009 (p < 0.05), but not in
2010. INTERPRETATION: Trans fatty acids were lower in 2009 relative to 2004, but
not different in 2010, suggesting that young Canadians may remain vulnerable to
partially hydrogenated vegetable oil exposure and that there is a need for
further monitoring of specific food categories and vulnerable populations.
PMID- 28401130
TI - Development of a preliminary essential medicines list for Canada.
AB - BACKGROUND: Some evidence supports the use of a short list of essential medicines
to improve prescribing. We aimed to create a preliminary essential medicines list
for use in Canada. METHODS: The 2013 World Health Organization Model List of
Essential Medicines was initially adapted by the research team. Fourteen Canadian
clinicians gave suggestions for changes to the list. Literature relevant to each
unique suggestion was gathered and presented to 3 clinician-scientists who used a
modified nominal group technique to make recommendations on the suggested
changes. Audits of prescriptions of 2 Toronto-based family health teams (an inner
city clinic and a suburban site) between Aug. 1, 2013, and July 30, 2014, were
performed to identify common prescriptions that were not on the draft list.
Literature relevant to these additional medications was gathered and shared with
the clinician-scientist review panel to determine whether each should be added to
the list, and a list was developed. The audits were repeated based on the final
list to provide a preliminary assessment of the coverage of the list. RESULTS:
The multistep process produced a list of 125 medications. The medications
included on this list covered 90.8% and 92.6% of prescriptions at the inner city
clinic and the suburban site, respectively. In total, 93% of the patients seen at
the inner city clinic and 96% of the patients seen at the suburban clinic had all
or all but 1 of their medications covered by the list. INTERPRETATION: A
preliminary list of essential medicines was developed that covered most, but not
all, prescriptions at 2 primary care sites. The list should be further refined
based on wider input.
PMID- 28401131
TI - Perceptions and experiences of a gender gap at a Canadian research institute and
potential strategies to mitigate this gap: a sequential mixed-methods study.
AB - BACKGROUND: The gender gap in academia is long-standing. Failure to ensure that
our academic faculty reflect our student pool and national population deprives
Canada of talent. We explored the gender distribution and perceptions of the
gender gap at a Canadian university-affiliated, hospital-based research
institute. METHODS: We completed a sequential mixed-methods study. In phase 1, we
used the research institute's registry of scientists (1999-2014) and estimated
overall prevalence of a gender gap and the gap with respect to job description
(e.g., associate v. full-time) and research discipline. In phase 2, we conducted
qualitative interviews to provide context for phase 1 data. Both purposive and
snowball sampling were used for recruitment. RESULTS: The institute included
30.1% (n = 62) women and 69.9% (n = 144) men, indicating a 39.8% gender gap. Most
full-time scientists (60.3%, n = 70) were clinicians; there were 54.2% more male
than female clinician scientists. Ninety-five percent of basic scientists were
men, indicating a 90.5% gap. Seven key themes emerged from 21 interviews,
including perceived impact of the gender gap, factors perceived to influence the
gap, recruitment trends, presence of institutional support, mentorship and
suggestions to mitigate the gap. Several factors were postulated to contribute to
the gender gap, including unconscious bias in hiring. INTERPRETATION: A
substantial gender gap exists within this research institute. Participants
identified strategies to address this gap, such as establishing transparent
search processes, providing opportunities for informal networking and mentorship
of female scientists and establishing institutional support for work-life
balance.
PMID- 28401132
TI - Comparing diagnostic classification of neurobehavioral disorder associated with
prenatal alcohol exposure with the Canadian fetal alcohol spectrum disorder
guidelines: a cohort study.
AB - BACKGROUND: Diagnostic criteria have recently been introduced in the Diagnostic
and Statistical Manual of Mental Disorders, 5th edition (DSM-5), for
neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). The
purpose of this study is to assess the classification of this condition using the
Canadian fetal alcohol spectrum disorder (FASD) multidisciplinary diagnostic
guidelines as the standard of comparison. First, classification of ND-PAE was
compared with Canadian FASD diagnoses of fetal alcohol syndrome (FAS), partial
FAS and alcohol-related neurodevelopmental disorder. Second, classification of ND
PAE was compared with FAS and pFAS only, a criterion for which includes facial
features highly predictive of prenatal alcohol exposure and effects. METHODS:
Eighty-two patients underwent multidisciplinary clinical evaluations using the
Canadian FASD diagnostic guidelines between 2011 and 2015. Two clinicians
independently reviewed patient files for evidence of diagnostic criteria for ND
PAE when applying an impairment cut-off level of 2 or more standard deviations
below the mean, or clinically significant impairment in the absence of
standardized norm-referenced measures. RESULTS: Good interrater reliability was
established between clinicians (kappa = 0.79). Classifications of ND-PAE and
Canadian FASD diagnoses, including alcohol-related neurodevelopmental disorder,
were moderately correlated (Cramer V [82] = 0.44, p < 0.01). However, ND-PAE
possessed low sensitivity in FASD identification. Further, there was no
correlation between ND-PAE and FAS/pFAS classifications (Cramer V [82] = 0.05, p
> 0.05). INTERPRETATION: Although there is considerable overlap between both sets
of criteria, ND-PAE was less likely to identify patients with FASD. Although the
neurobehavioral domains assessed by ND-PAE are supported in research, its
diagnostic structure restricts the identification of FASD at the impairment
threshold of 2 or more standard deviations. A disconnect remains with regard to
impairment thresholds between FASD, which relies on neurodevelopmental data, and
ND-PAE, which relies on clinical judgment.
PMID- 28401133
TI - Fatal overdoses involving hydromorphone and morphine among inpatients: a case
series.
AB - BACKGROUND: Opioids have narrow therapeutic windows, and errors in ordering or
administration can be fatal. The purpose of this study was to describe deaths
involving hydromorphone and morphine, which have similar-sounding names, but
different potencies. METHODS: In this case series, we describe deaths of patients
admitted to hospital or residents of long-term care facilities that involved
hydromorphone and morphine. We searched for deaths referred to the Patient Safety
Review Committee of the Office of the Chief Coroner for Ontario between 2007 and
2012, and subsequently reviewed by 2014. We reviewed each case to identify
intervention points where errors could have been prevented. RESULTS: We
identified 8 cases involving decedents aged 19 to 91 years. The cases involved
errors in prescribing, order processing and transcription, dispensing,
administration and monitoring. For 7 of the 8 cases, there were multiple (2 or
more) possible intervention points. Six cases may have been prevented by
additional patient monitoring, and 5 cases involved dispensing errors.
INTERPRETATION: Opioid toxicity deaths in patients living in institutions can be
prevented at multiple points in the prescribing and dispensing processes.
Interventions aimed at preventing errors in hydromorphone and morphine
prescribing, administration and patient monitoring should be implemented and
rigorously evaluated.
PMID- 28401134
TI - Preconsult interactive computer-assisted client assessment survey for common
mental disorders in a community health centre: a randomized controlled trial.
AB - BACKGROUND: Access disparities for mental health care exist for vulnerable
ethnocultural and immigrant groups. Community health centres that serve these
groups could be supported further by interactive, computer-based, self
assessments. METHODS: An interactive computer-assisted client assessment survey
(iCCAS) tool was developed for preconsult assessment of common mental disorders
(using the Patient Health Questionnaire [PHQ-9], Generalized Anxiety Disorder 7
item [GAD-7] scale, Primary Care Post-traumatic Stress Disorder [PTSD-PC] screen
and CAGE [concern/cut-down, anger, guilt and eye-opener] questionnaire), with
point-of-care reports. The pilot randomized controlled trial recruited adult
patients, fluent in English or Spanish, who were seeing a physician or nurse
practitioner at the partnering community health centre in Toronto. Randomization
into iCCAS or usual care was computer generated, and allocation was concealed in
sequentially numbered, opaque envelopes that were opened after consent. The
objectives were to examine the interventions' efficacy in improving mental health
discussion (primary) and symptom detection (secondary). Data were collected by
exit survey and chart review. RESULTS: Of the 1248 patients assessed, 190 were
eligible for participation. Of these, 148 were randomly assigned (response rate
78%). The iCCAS (n = 75) and usual care (n = 72) groups were similar in
sociodemographics; 98% were immigrants, and 68% were women. Mental health
discussion occurred for 58.7% of patients in the iCCAS group and 40.3% in the
usual care group (p <= 0.05). The effect remained significant while controlling
for potential covariates (language, sex, education, employment) in generalized
linear mixed model (GLMM; adjusted odds ratio [OR] 2.2; 95% confidence interval
[CI] 1.1-4.5). Mental health symptom detection occurred for 38.7% of patients in
the iCCAS group and 27.8% in the usual care group (p > 0.05). The effect was not
significant beyond potential covariates in GLMM (adjusted OR 1.9; 95% CI 0.9
4.1). INTERPRETATION: The studied intervention holds potential for community
health centres to improve mental health discussion. Further research with larger
samples should examine the impact on detection and enhance generalizability.
Trial registration: ClinicalTrials.gov, no: NCT02023957, registered on Dec. 12,
2013.
PMID- 28401135
TI - The effects of catastrophic drug plan deductibles on older women's use of
cardiovascular medicines: a retrospective cohort study.
AB - BACKGROUND: In recent years, some provinces have implemented income-based
catastrophic drug coverage in an effort to provide universal drug coverage while
limiting government liability for the escalating costs of medicines needed for an
aging population. We sought to examine the effects of income-based deductibles
under British Columbia's Fair PharmaCare system on older patients' use of
cardiovascular medicines in 2013, 10 years after the province's policy change.
METHODS: Using linked administrative databases, we studied rates of hypertension
and cholesterol medication used by 2 cohorts of older, married women who had
different levels of public drug subsidy based solely on their spouses' ages. We
compare measures of 2013 medication use by study cohorts using statistical models
that controlled for age, general health status, indicators of need for specific
drug classes, ethnicity, rural residence and household income. RESULTS: Among
members of our study cohorts, the odds of filling cardiovascular prescriptions in
2013 were influenced by patient age, general health status, drug-specific
diagnoses, ethnicity, place of residence and household income. For women with
household incomes less than $50 000 (42% of our study population), having
preferential public drug coverage by way of spousal age was associated with a 15%
increase in the adjusted odds of filling 1 or more prescription for hypertension
treatment (adjusted odds ratio [OR] 1.15, 95% confidence interval [CI] 1.06 to
1.24) and a 13% increase in the adjusted odds of filling 1 or more prescription
for cholesterol treatments (adjusted OR 1.13, 95% CI 1.06 to 1.21). There were no
statistically significant effects on the number of days of therapy purchased per
user of these cardiovascular medicines. INTERPRETATION: We have found that the
level of income-based deductibles under catastrophic drug benefi t plans can
affect the use of cardiovascular drug treatments, even long after deductibles are
put in place. These results add to the body of evidence in support of the idea
that public drug coverage design can affect access to necessary medications.
PMID- 28401137
TI - Changes in breastfeeding initiation at hospital discharge between first and
second births in Nova Scotia: a population-based cohort study.
AB - BACKGROUND: Breastfeeding has well-recognized health benefits for infants and
mothers. However, little research has been conducted to investigate changes in
breastfeeding from one pregnancy to another. This study was conducted to describe
rates of breastfeeding initiation at hospital discharge for women's first and
second births and to identify factors associated with changes in initiation at
the second birth. METHODS: We conducted a longitudinal, population-based cohort
study involving women residing in Nova Scotia who delivered a first and second
live-born singleton between 2007 and 2013. Separate analyses were conducted among
women who breastfed their first infant and among women who did not breastfeed
their first infant. RESULTS: Of the 9643 (82.6%) mothers who initiated
breastfeeding in the first birth, 973 (10.3%) did not initiate breastfeeding in
the second birth. Of first-birth noninitiators, 526 (26.3%) initiated
breastfeeding in the second birth. With the exception of smoking and cesarean
births, factors that were associated with breastfeeding initiation in the second
birth depended on breastfeeding initiation status in the first birth. These
factors were associated with increased odds of not breastfeeding in the second
birth among the subset of mothers who breastfed in the first birth, and decreased
odds of breastfeeding in the second birth among the subset of mothers who did not
breastfeed in the first birth. INTERPRETATION: Most women continue the same
method of infant feeding after their first and second births. Identifying factors
associated with change in breastfeeding status between the first and second
births may help to inform interventions for optimal breastfeeding initiation in
the second birth.
PMID- 28401136
TI - Patient, family physician and community pharmacist perspectives on expanded
pharmacy scope of practice: a qualitative study.
AB - BACKGROUND: The RxEACH trial was a randomized trial to evaluate the efficacy of
community pharmacy-based case finding and intervention in patients at high risk
for cardiovascular (CV) events. Community-dwelling patients with poorly
controlled risk factors were identified and their CV risk reduced through patient
education, prescribing and follow-up by their pharmacist. Perspectives of
patients, family physicians and community pharmacists were obtained regarding
pharmacists' identification and management of patients at high risk for CV
events, to identify strategies to facilitate implementation of the pharmacist's
expanded role in routine patient care. METHODS: We used a qualitative methodology
(individual semistructured interviews) with conventional qualitative content
analysis to describe perceptions about community pharmacists' care of patients at
high risk for CV events. Perceptions were categorized into macro (structure),
meso (institution) and micro (practice) health system levels, based on a
conceptual framework of care for optimizing scopes of practice. RESULTS: We
interviewed 48 participants (14 patients, 13 family physicians and 21 community
pharmacists). Patients were supportive of the expanded scope of practice of
pharmacists. All participant groups emphasized the importance of communication,
ability to share patient information, trust and better understanding of the
roles, responsibilities, accountabilities and liabilities of the pharmacist
within their expanded role. INTERPRETATION: Despite support from patients and
changes to delivery of care in primary care settings, ongoing efforts are needed
to understand how to best harmonize family physician and community pharmacist
roles across the health system. This will require collaboration and input from
professional associations, regulatory bodies, pharmacists, family physicians and
patients.
PMID- 28401138
TI - Prevalence of symptoms at the end of life in an acute care hospital: a
retrospective cohort study.
AB - BACKGROUND: There is currently debate over the benefits and harms of physician
assisted death. One of the factors influencing this debate is concern about
symptoms in the days before death. The objective of this study was to describe
the frequency of symptoms before death and determine patient characteristics
associated with these symptoms. METHODS: We reviewed the medical record of every
patient who died at a multisite academic teaching hospital over a 3-month period.
We determined the number of episodes of pain, dyspnea, agitation and nausea
during the final 48 hours of life and assessed the patient and encounter
characteristics associated with 2 or more episodes of symptoms. RESULTS: A total
of 480 patients died during the study period. Of these patients, 29.2% (140/480)
had 2 or more symptoms in the final 48 hours of life. Higher Elixhauser
comorbidity scores (relative risk [RR] 1.35, 95% confidence interval [CI] 1.23
1.49), having a family doctor (RR 2.33, 95% CI 1.02-5.38), being admitted to the
medical oncology service (RR 1.51, 95% CI 1.11-2.05) and having a documented
order for no resuscitation written early during the stay in hospital (RR 1.38,
95% CI 1.01-1.89) were independently associated with symptoms. Admission to
intensive care was associated with fewer symptoms (RR 0.39, CI 95% 0.19-0.80).
INTERPRETATION: Symptoms are common in the final 48 hours of life, particularly
in patients with multimorbidity who want limitations on the aggressiveness of
their care. An integrated palliative approach is needed for select at-risk
patients.
PMID- 28401139
TI - Family physician-led, team-based, lifestyle intervention in patients with
metabolic syndrome: results of a multicentre feasibility project.
AB - BACKGROUND: Metabolic syndrome (MetS) is a medical condition with major
complications and health care costs. Previous research has shown that diet and
exercise can improve and reverse this condition. The goal of this study was to
test the feasibility and effectiveness of implementing the Canadian Health
Advanced by Nutrition and Graded Exercise (CHANGE) program into diverse family
medicine practices to improve MetS. METHODS: In this longitudinal before-after
study, 305 adult patients with MetS were recruited from 3 diverse family medicine
team-based organizations to the CHANGE personalized diet and exercise program.
Participants were followed for 12 months. Primary outcomes included feasibility
and reversal of MetS. Secondary outcomes included improvement in MetS components,
changes in diet quality, aerobic fitness and cardiovascular risk. RESULTS:
Participants attended 76% and 90% of the kinesiologist and dietitian visits,
respectively. At 12 months, 19% of patients (95% confidence interval [CI] 14%
24%) showed reversal of MetS, VO2max increased by 16% (95% CI 13%-18%), and
Healthy Eating Index and Mediterranean Diet Scores improved by 9.6% (95% CI 7.6%
11.6%) and 1.4% (1.1%-1.6%), respectively. In addition, the Prospective
Cardiovascular Munster (PROCAM) 10-year risk of acute coronary event decreased by
1.4%, from a baseline of 8.6%. INTERPRETATION: A team-based program led by the
family physician that educates patients about the risks of MetS, and with a
dietitian and kinesiologist, empowers them to undertake an individualized
supervised program of diet modification and exercise, is feasible, improves
aerobic capacity and diet quality, reverses MetS and improves MetS components at
12 months.
PMID- 28401140
TI - The Canadian minimum dataset for chronic low back pain research: a cross-cultural
adaptation of the National Institutes of Health Task Force Research Standards.
AB - BACKGROUND: To better standardize clinical and epidemiological studies about the
prevalence, risk factors, prognosis, impact and treatment of chronic low back
pain, a minimum data set was developed by the National Institutes of Health (NIH)
Task Force on Research Standards for Chronic Low Back Pain. The aim of the
present study was to develop a culturally adapted questionnaire that could be
used for chronic low back pain research among French-speaking populations in
Canada. METHODS: The adaptation of the French Canadian version of the minimum
data set was achieved according to guidelines for the cross-cultural adaptation
of self-reported measures (double forward-backward translation, expert committee,
pretest among 35 patients with pain in the low back region). Minor cultural
adaptations were also incorporated into the English version by the expert
committee (e.g., items about race/ethnicity, education level). RESULTS: This
cross-cultural adaptation provides an equivalent French-Canadian version of the
minimal data set questionnaire and a culturally adapted English-Canadian version.
Modifications made to the original NIH minimum data set were minimized to
facilitate comparison between the Canadian and American versions. INTERPRETATION:
The present study is a first step toward the use of a culturally adapted
instrument for phenotyping French- and English-speaking low back pain patients in
Canada. Clinicians and researchers will recognize the importance of this
standardized tool and are encouraged to incorporate it into future research
studies on chronic low back pain.
PMID- 28401141
TI - Knowledge, attitude, willingness and readiness of primary health care providers
to provide oral health services to children in Niagara, Ontario: a cross
sectional survey.
AB - BACKGROUND: Most children are exposed to medical, but not dental, care at an
early age, making primary health care providers an important player in the
reduction of tooth decay. The goal of this research was to understand the
feasibility of using primary health care providers in promoting oral health by
assessing their knowledge, attitude, willingness and readiness in this regard.
METHODS: Using the Dillman method, a mail-in cross-sectional survey was conducted
among all family physicians and pediatricians in the Niagara region of Ontario
who have primary contact with children. A descriptive analysis was performed.
RESULTS: Close to 70% (181/265) of providers responded. More than 90% know that
untreated tooth decay could affect the general health of a child. More than 80%
examine the oral cavity for more than 50% of their child patients. However, more
than 50% are not aware that white spots or lines on the tooth surface are the
first signs of tooth decay. Lack of clinical time was the top reason for not
performing oral disease prevention measures. INTERPRETATION: Overall, survey
responses show a positive attitude and willingness to engage in the oral health
of children. To capitalize on this, there is a need to identify mechanisms of
providing preventive oral health care services by primary health care providers;
including improving their knowledge of oral health and addressing other potential
barriers.
PMID- 28401142
TI - Comprehensive survey of household radon gas levels and risk factors in southern
Alberta.
AB - BACKGROUND: The inhalation of naturally occurring radon (222Rn) gas from indoor
air exposes lung tissue to alpha-particle bombardment, a highly mutagenic form of
ionizing radiation that damages DNA and increases the lifetime risk of lung
cancer. We analyzed household radon concentrations and risk factors in southern
Alberta, including Calgary, the third-largest Canadian metropolis. METHODS: A
total of 2382 residential homes (2018 in Calgary and 364 in surrounding
townships) from an area encompassing 82% of the southern Alberta population were
tested for radon, per Health Canada guidelines, for at least 90 days (median 103
d) between 2013 and 2016. Participants also provided home metrics (construction
year, build type, foundation type, and floor and room of deployment of the radon
detector) via an online survey. Homes that were subsequently remediated were
retested to determine the efficacy of radon reduction techniques in the region.
RESULTS: The average indoor air radon level was 126 Bq/m3, which equates to an
effective absorbed radiation dose of 3.2 mSv/yr. A total of 1135 homes (47.6%)
had levels of 100 Bq/m3 or higher, and 295 homes (12.4%) had levels of 200 Bq/m3
or higher; the range was less than 15 Bq/m3 to 3441 Bq/m3. Homes built in 1992 or
later had radon levels 31.5% higher, on average, than older homes (mean 142 Bq/m3
v. 108 Bq/m3). For 90 homes with an average radon level of 575 Bq/m3 before
mitigation, radon suppression successfully reduced levels to an average of 32.5
Bq/m3. INTERPRETATION: Our findings show that radon exposure is a genuine public
health concern in southern Alberta, suggest that modern building practices are
associated with increased indoor air radon accumulation, legitimatize efforts to
understand the consequences of radon exposure to the public, and suggest that
radon testing and mitigation are likely to be impactful cancer prevention
strategies.
PMID- 28401143
TI - Impact of abiraterone acetate with and without prior docetaxel chemotherapy on
the survival of patients with metastatic castration-resistant prostate cancer: a
population-based study.
AB - BACKGROUND: Abiraterone acetate was introduced in Quebec in 2012 for the
treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients
who had received chemotherapy with docetaxel. This study describes abiraterone
use in the early postapproval period and its clinical effectiveness in Quebec,
for both patients who had received docetaxel chemotherapy and those who could not
receive docetaxel therapy owing to medical reasons. METHODS: A retrospective
cohort study was conducted using Quebec public health care administrative
databases. Our cohort consisted of patients with mCRPC who received abiraterone
between January 2012 and June 2013. Treatment groups were defined as patients who
received abiraterone following docetaxel chemotherapy and those who received
abiraterone without having had chemotherapy, under the "exception patient"
measure. Study outcomes included overall survival, duration of abiraterone
therapy and number of hospital days. Cox proportional hazard regression was used
to estimate the effectiveness of abiraterone adjusted for several covariates.
RESULTS: Our cohort consisted of 303 patients with mCRPC treated with abiraterone
(99 after chemotherapy and 204 as exception patients). The median age at
initiation of abiraterone therapy was 75.0 for the postchemotherapy group and
80.0 for the exception patient group. The corresponding median survival values
were 12 and 14 months (log-rank test p = 0.8). Risk of death was similar in the 2
groups (adjusted hazard ratio 0.89 [95% confidence interval 0.57-1.38]).
INTERPRETATION: The effectiveness of abiraterone in older patients who were
ineligible for chemotherapy was similar to that of patients with prior docetaxel
exposure. Overall, the real-world survival benefits of abiraterone were similar
to those in the COU-AA-301 trial.
PMID- 28401145
TI - Porous and Magnetic Molecularly Imprinted Polymers via Pickering High Internal
Phase Emulsions Polymerization for Selective Adsorption of lambda-Cyhalothrin.
AB - A novel macroporous magnetic molecularly imprinted polymer (MMIPs) of was
prepared by W/O Pickering (high internal phase emulsions) HIPEs polymerization,
and then it was adopted as adsorbent for selective adsorption of lambda
cyhalothrin (LC). In static conditions, adsorption capacity of LC increased
rapidly in the first 60 min and reached to equilibrium in ~2.0 h. Excellent
conformity of the second-order model confirmed the chemical nature of the
interaction between the LC and imprinted sites. The fitting adsorption isotherm
was a Langmuir type, and the maximum monolayer adsorption capacity at 298 K was
404.4 MUmol g-1. Thermodynamic parameters suggested the specific adsorption at
298 K was an exothermic, spontaneous, and entropy decreased process. Competitive
recognition studies of the MMIPs were performed with diethyl phthalate (DEP) and
the structurally similar compound fenvalerate (FL), and the MMIPs, which
displayed high selectivity for LC.
PMID- 28401144
TI - Insights into the Activity Change of Spore Photoproduct Lyase Induced by
Mutations at a Peripheral Glycine Residue.
AB - UV radiation triggers the formation of 5-thyminyl-5,6-dihydrothymine, i.e., the
spore photoproduct (SP), in the genomic DNA of bacterial endospores. These SPs,
if not repaired in time, may lead to genome instability and cell death. SP is
mainly repaired by spore photoproduct lyase (SPL) during spore outgrowth via an
unprecedented protein-harbored radical transfer pathway that is composed of at
least a cysteine and two tyrosine residues. This mechanism is consistent with the
recently solved SPL structure that shows all three residues are located in
proximity and thus able to participate in the radical transfer process during the
enzyme catalysis. In contrast, an earlier in vivo mutational study identified a
glycine to arginine mutation at the position 168 on the B. subtilis SPL that is
>15 A away from the enzyme active site. This mutation appears to abolish the
enzyme activity because endospores carrying this mutant were sensitive to UV
light. To understand the molecular basis for this rendered enzyme activity, we
constructed two SPL mutations G168A and G168R, examined their repair of
dinucleotide SP TpT, and found that both mutants exhibit reduced enzyme activity.
Comparing with the wildtype (WT) SPL enzyme, the G168A mutant slows down the SP
TpT repair by 3~4-fold while the G168R mutant by ~ 80-fold. Both mutants exhibit
a smaller apparent (DV) kinetic isotope effect (KIE) but a bigger competitive
(DV/K) KIE than that by the WT SPL. Moreover, the G168R mutant also produces a
large portion of the abortive repair product TpT-[Formula: see text]; the
formation of which indicates that cysteine 141 is no longer well positioned as
the H-donor to the thymine allylic radical intermediate. All these data imply
that the mutation at the remote glycine 168 residue alters the enzyme 3D
structure, subsequently reducing the SPL activity by changing the positions of
the essential amino acids involved in the radical transfer process.
PMID- 28401146
TI - Effects of Bunch Rot (Botrytis cinerea) and Powdery Mildew (Erysiphe necator)
Fungal Diseases on Wine Aroma.
AB - This study aimed to characterize the effects of bunch rot and powdery mildew on
the primary quality parameter of wine, the aroma. The influence of these fungal
diseases was studied by comparative Aroma Extract Dilution Analyses (AEDA) and
sensory tests. The effect of bunch rot was investigated on three grape varieties,
namely White Riesling, Red Riesling and Gewurztraminer and that of powdery mildew
on the hybrid Gm 8622-3; thereby, samples were selected that showed pronounced
cases of infection to elaborate potential currently unknown effects. Both
infections revealed aromatic differences induced by these fungi. The sensory
changes were not associated with one specific compound only, but were due to
quantitative variations of diverse substances. Bunch rot predominantly induced an
increase in the intensities of peach-like/fruity, floral and liquor-like/toasty
aroma notes. These effects were found to be related to variations in aroma
substance composition as monitored via AEDA, mainly an increase in the FD factors
of lactones and a general moderate increase of esters and alcohols. On the other
hand, powdery mildew decreased the vanilla-like character of the wine while the
remaining sensory attributes were rather unaffected. Correspondingly, FD factors
of the main aroma constituents were either the same or only slightly modified by
this disease. Moreover, bunch rot influenced the aroma profiles of the three
varieties studied to a different degree. In hedonic evaluation, bunch rot
affected samples were rated as being more pleasant in comparison to their healthy
controls in all three varieties while the powdery mildew-affected sample was
rated as being less pleasant than its healthy control.
PMID- 28401147
TI - Toxinotyping and Sequencing of Clostridium difficile Isolates from Patients in a
Tertiary Care Hospital of Northern India.
AB - BACKGROUND: Clostridium difficile is an important cause of infectious colitis
among hospitalized patients across the globe. The pathogenic potential of C.
difficile in producing significant morbidity and mortality is mainly due to
production of toxins A and B. The outbreaks of C. difficile infection (CDI) are
due to changes in the genetic sequences of the organism. There is hardly any
molecular study reported on the prevalent types of C. difficile strains in India.
Toxinotyping and sequencing of locally circulating C. difficile isolates from
patients presenting to our tertiary care center of North India were done.
MATERIALS AND METHODS: C. difficile strains (n = 174) isolated from 1,110 fecal
samples from patients with suspected CDI were subjected to toxinotyping and
partial sequencing of tcdA and tcdB genes. Comparison of nucleotide sequences
with reference C. difficile 630 strain using BLAST was made and translated into
corresponding amino acid sequences by ExPASy. RESULTS AND DISCUSSION: Of 174 C.
difficile isolates, 121 were toxigenic, belonging to toxinotype 0 (n = 76) and
VIII (n = 45). Partial sequencing of toxin genes using bioinformatics approaches
revealed changes in toxin A sequences of five (50%) C. difficile isolates, but
the translated nucleotide sequences showed substitution in only three of them. No
variation was seen in the toxin B nucleotide sequences. Interstrain variations
were found in the clinical C. difficile isolates in our region. CONCLUSION: PCR
amplified toxigenic genes followed by sequencing can help to identify genetic
changes and pathogenicity of varied collection of C. difficile isolates.
PMID- 28401149
TI - Testing for HIV/STIs in China: Challenges, Opportunities, and Innovations.
PMID- 28401150
TI - Evidence in Urologic- and Pelvic-Surgery Research: Finding the IDEAL Way of
Reporting.
PMID- 28401148
TI - New Insights into the Epigenetics of Hepatocellular Carcinoma.
AB - Hepatocellular Carcinoma (HCC) is one of the most predominant malignancies with
high fatality rate. This deadly cancer is rising at an alarming rate because it
is quite resistant to radio- and chemotherapy. Different epigenetic mechanisms
such as histone modifications, DNA methylation, chromatin remodeling, and
expression of noncoding RNAs drive the cell proliferation, invasion, metastasis,
initiation, progression, and development of HCC. These epigenetic alterations
because of potential reversibility open way towards the development of biomarkers
and therapeutics. The contribution of these epigenetic changes to HCC development
has not been thoroughly explored yet. Further research on HCC epigenetics is
necessary to better understand novel molecular-targeted HCC treatment and
prevention. This review highlights latest research progress and current updates
regarding epigenetics of HCC, biomarker discovery, and future preventive and
therapeutic strategies to combat the increasing risk of HCC.
PMID- 28401151
TI - White Matter Integrity in Genetic High-Risk Individuals and First-Episode
Schizophrenia Patients: Similarities and Disassociations.
AB - White matter (WM) neuroimaging studies have shown varied findings at different
stages of schizophrenia (SZ). Understanding these variations may elucidate
distinct markers of genetic vulnerability and conversion to psychosis. To examine
the similarities and differences in WM connectivity between those at-risk for and
in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48
individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals
at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was
conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC),
anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR
SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus
(SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both
GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA
was significantly positively correlated with hallucinations, and right SLF II was
positively correlated with thought disorder. The presence of shared WM deficits
in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ,
while the disparate FA changes in the FE-SZ group may represent symptom
generating circuitry that mediates perceptual and cognitive disturbances of SZ
and ultimately culminates in the onset of psychotic episodes.
PMID- 28401152
TI - Hemodynamic Analysis of Pediatric Septic Shock and Cardiogenic Shock Using
Transpulmonary Thermodilution.
AB - Septic shock and cardiogenic shock are the two most common types of shock in
children admitted to pediatric intensive care units (PICUs). The aim of the study
was to investigate which hemodynamic variables were associated with mortality in
children with shock. We retrospectively analyzed 50 children with shock (37
septic shock cases and 13 cardiogenic shock cases) in the PICU and monitored
their hemodynamics using transpulmonary thermodilution from 2003 to 2016.
Clinical factors were analyzed between the patients with septic and cardiogenic
shock. In addition, hemodynamic parameters associated with mortality were
analyzed. The 28-day mortality was significantly higher in the septic group than
in the cardiogenic group (p = 0.016). Initially, the parameters of cardiac output
and cardiac contractility were higher in the septic group (p < 0.05) while the
parameters of preload and afterload were all higher in the cardiogenic group (p <
0.05). Cardiac index was significantly lower in the nonsurvivors of cardiogenic
shock at the time of initial admission and after the first 24 hours (both p <
0.05), while systemic vascular resistance index (SVRI) was significantly lower in
the nonsurvivors of septic shock (p < 0.001). Therefore, during the first 24
hours after intensive care, SVRI and cardiac index are the most important
hemodynamic parameters associated with mortality.
PMID- 28401153
TI - Metals Are Important Contact Sensitizers: An Experience from Lithuania.
AB - Background. Metals are very frequent sensitizers causing contact allergy and
allergic contact dermatitis worldwide; up-to-date data based on patch test
results has proved useful for the identification of a problem. Objectives. In
this retrospective study prevalence of contact allergy to metals (nickel,
chromium, palladium, gold, cobalt, and titanium) in Lithuania is analysed.
Patients/Methods. Clinical and patch test data of 546 patients patch tested in
2014-2016, in Vilnius University Hospital Santariskiu Klinikos, was analysed and
compared with previously published data. Results. Almost third of tested patients
(29.56%) were sensitized to nickel. Younger women were more often sensitized to
nickel than older ones (36% versus 22.8%, p = 0.0011). Women were significantly
more often sensitized to nickel than men (33% versus 6.1%, p < 0.0001). Younger
patients were more often sensitized to cobalt (11.6% versus 5.7%, p = 0.0183).
Sensitization to cobalt was related to sensitization to nickel (p < 0.0001). Face
dermatitis and oral discomfort were related to gold allergy (28% versus 6.9%
dermatitis of other parts, p < 0.0001). Older patients were patch test positive
to gold(I) sodium thiosulfate statistically significantly more often than younger
ones (44.44% versus 21.21%, p = 0.0281). Conclusions. Nickel, gold, cobalt, and
chromium are leading metal sensitizers in Lithuania. Cobalt sensitization is
often accompanied by sensitization to nickel. Sensitivity rate to palladium and
nickel indicates possible cross-reactivity. No sensitization to titanium was
found.
PMID- 28401154
TI - Cytotoxicity and Antimicrobial Activity of Oral Rinses In Vitro.
AB - While oral rinses used for cosmetic purposes only do not necessarily have to be
antiseptic, antimicrobial activity is required for medical indications, including
oral and periodontal surgery. So the question arises-is the antimicrobial
activity of oral rinses associated with any destructive changes in cell viability
in vitro? To answer this question, we examined twelve oral rinses with respect to
their antimicrobial and cytotoxic activity. Antimicrobial activity was screened
against five bacterial strains using disc diffusion. Cytotoxicity was determined
by mitochondrial reductase activity with primary gingival fibroblasts, L929
cells, and HSC-2 epithelial cells. Phase contrast microscopy and trypan blue
staining were then performed to reveal cell morphology. Cells remained vital
after exposure to oral rinses that were only used for cosmetic purposes. Moderate
cytotoxic effects were observed for oral rinses containing 0.05% chlorhexidine,
ethanol, or pegylated hydrogenated castor oil and sodium dodecyl sulfate. Other
oral rinses containing 0.2% chlorhexidine and cocamidopropyl betaine exhibited
strong cytotoxic and antimicrobial activity. Strong cytotoxic but moderate
antimicrobial activity was observed in oral rinses containing cetylpyridinium
chloride. The in vitro data show that oral rinses are heterogeneous with respect
to their cytotoxic and antimicrobial effects. Based on their respective
properties, oral rinses can be selected either to reduce the microbial load or
for cosmetic purposes.
PMID- 28401155
TI - Identification of Streptococcus pneumoniae: Development of a Standardized
Protocol for Optochin Susceptibility Testing Using Total Lab Automation.
AB - Purpose. Optochin susceptibility is one parameter used in the laboratory to
identify Streptococcus pneumoniae. However, a single standardized procedure does
not exist. Optochin is included neither in the current EUCAST breakpoint tables
nor in the CLSI performance standards for antimicrobial susceptibility testing.
We wanted to establish an evidence-based protocol for optochin testing for our
Total Lab Automation. Methods. We tested seven different agars and four different
reading time points (7 h, 12 h, 18 h, and 24 h). To accommodate for serotype
diversity, all tests were done with 99 different strains covering 34 different
serotypes of S. pneumoniae. We calculated a multivariable linear regression using
data from 5544 inhibition zones. Results. Reading was possible for all strains at
12 h. Agar type and manufacturer influenced the size of the inhibition zones by
up to 2 mm and they varied considerably depending on serotype (up to 3 mm for
serotype 3). Depending on agar and reading time point, up to 38% of inhibition
zones were smaller than the cut-off of 14 mm; that is, the result of the test was
false-negative. Conclusions. Shortening incubation time from 24 h to 12 h for
optochin susceptibility testing is feasible. Agar and incubation time have to be
chosen carefully to avoid false-negative results.
PMID- 28401156
TI - Computational Identification and Characterization of a Promiscuous T-Cell Epitope
on the Extracellular Protein 85B of Mycobacterium spp. for Peptide-Based Subunit
Vaccine Design.
AB - Tuberculosis (TB) is a reemerging disease that remains as a leading cause of
morbidity and mortality in humans. To identify and characterize a T-cell epitope
suitable for vaccine design, we have utilized the Vaxign server to assess all
antigenic proteins of Mycobacterium spp. recorded to date in the Protegen
database. We found that the extracellular protein 85B displayed the most robust
antigenicity among the proteins identified. Computational tools for identifying T
cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to
at least 13 major histocompatibility complexes, revealing the promiscuous nature
of the epitope. Molecular docking simulation demonstrated that the epitope could
bind to the binding groove of MHC II and MHC I molecules by several hydrogen
bonds. Molecular docking analysis further revealed that the epitope had a
distinctive binding pattern to all DRB1 and A and B series of MHC molecules and
presented almost no polymorphism in its binding site. Moreover, using "Allele
Frequency Database," we checked the frequency of HLA alleles in the worldwide
population and found a higher frequency of both class I and II HLA alleles in
individuals living in TB-endemic regions. Our results indicate that the
identified peptide might be a universal candidate to produce an efficient epitope
based vaccine for TB.
PMID- 28401157
TI - Engineering of Systematic Elimination of a Targeted Chromosome in Human Cells.
AB - Embryonic trisomy leads to abortion or congenital genetic disorders in humans.
The most common autosomal chromosome abnormalities are trisomy of chromosomes 13,
18, and 21. Although alteration of gene dosage is thought to contribute to
disorders caused by extra copies of chromosomes, genes associated with specific
disease phenotypes remain unclear. To generate a normal cell from a trisomic cell
as a means of etiological analysis or candidate therapy for trisomy syndromes, we
developed a system to eliminate a targeted chromosome from human cells.
Chromosome 21 was targeted by integration of a DNA cassette in HeLa cells that
harbored three copies of chromosome 21. The DNA cassette included two inverted
loxP sites and a herpes simplex virus thymidine kinase (HSV-tk) gene. This system
causes missegregation of chromosome 21 after expression of Cre recombinase and
subsequently enables the selection of cells lacking the chromosome by culturing
in a medium that includes ganciclovir (GCV). Cells harboring only two copies of
chromosome 21 were efficiently induced by transfection of a Cre expression
vector, indicating that this approach is useful for eliminating a targeted
chromosome.
PMID- 28401158
TI - Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated
Intervertebral Discs.
AB - Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes
(P. acnes), have been thought to be a new pathogeny for a series of disc
diseases. However, until now, there has been no histological evidence to confirm
this link. The purpose of this study was to confirm the presence of P. acnes in
nonpyogenic intervertebral discs via histological observation. Method.
Degenerated intervertebral discs were harvested from 76 patients with low back
pain and/or sciatica but without any symptoms of discitis or spondylodiscitis.
The samples were cultured under anaerobic conditions and then examined using 16S
rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were
stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and
observed under a microscope. Results. Here, 16 intervertebral discs were found to
be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76).
Among them, 7 samples had visible microbes stained with HE and modified Brown
Brenn staining. Morphological examination showed the bacteria to be Gram-positive
and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable
of colonizing some degenerated intervertebral discs without causing discitis, and
its presence could be further confirmed by histological evidence. Targeting these
bacteria may be a promising therapy method for some disc diseases.
PMID- 28401159
TI - Management of Hepple Stage V Osteochondral Lesion of the Talus with a Platelet
Rich Plasma Scaffold.
AB - There has been no consensus on the treatment or prognosis of Hepple stage V
osteochondral lesions of the talus (OLTs), especially for lesions greater than
1.5 cm2 in size. The objective of this study was to investigate the clinical
outcomes achieved upon application of a platelet-rich plasma (PRP) scaffold with
a cancellous bone autograft for Hepple stage V OLTs. Fourteen patients (mean age,
39 years) were treated with a cancellous bone graft and a PRP scaffold between
2013 and 2015. The mean time to surgical treatment was 23.5 months. Ankle X-ray
and magnetic resonance imaging were performed at the final follow-up. Functional
outcomes were evaluated according to the Visual Analog Scale (VAS) score,
American Orthopaedic Foot and Ankle Society (AOFAS) score, and Short Form 36 (SF
36) score. The range of motion (ROM) of the ankle joint and complications also
were recorded. Thirteen patients completed the full follow-up, with a mean follow
up duration of 18 months. MRI demonstrated the complete regeneration of
subchondral bone and cartilage in all patients. The postoperative VAS, AOFAS
ankle and hindfoot, and SF-36 scores were improved significantly (all P < 0.001)
without obvious complications. We suggest that, for the Hepple stage V OLTs,
management with cancellous bone graft and PRP scaffold may be a safe and
effective treatment.
PMID- 28401160
TI - Posttransplant Anemia as a Prognostic Factor of Mortality in Kidney-Transplant
Recipients.
AB - Background. Findings on the association between posttransplant anemia (PTA) and
mortality in posttransplant patients are scarce. This study explored whether PTA
shortly after kidney transplantation (KT) predicts mortality at up to 10 years'
follow-up, stratified for chronic kidney disease (CKD) stages. Methods. PTA was
divided into 3 categories according to the hemoglobin (Hb) value: severe (Hb < 10
g/dl), mild (10.0 g/dl <= Hb < 11.9 g/dl), or no PTA (Hb >= 12 g/dl). CKD stages
were estimated using the CKD-EPI formula and divided into 2 groups: CKD1-2 and
CKD3-5. Cox regression, stratified according to CKD, was performed to identify
whether different categories of PTA predicted mortality in KT recipients.
Results. Age, being female, and both mild and severe PTA contributed
significantly to the Cox regression model on mortality in CKD1-2. In the Cox
regression model for mortality in CKD3-5, age and severe PTA contributed
significantly to this model. Conclusion. PTA shortly after KT increased the risk
of mortality at up to 10 years' follow-up. Even mild PTA is associated with a 6
fold higher risk of mortality and severe PTA with a 10-fold higher risk of
mortality in CKD1-2. Clinical evaluation and treatment of anemia might reduce the
higher risk of mortality in patients with PTA in early stages of CKD after KT.
PMID- 28401161
TI - Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult
Virgin Rats: A Histological Study.
AB - Background. Our previous Grafenberg spot findings confirmed that the distal-third
areas of the anterior vaginal wall bore a significantly greater number of nerves
and sexual hormone may have certain degree of influence on these significant
differences. However, the role of estrogen in vaginal innervations remains
controversial. Methods. To investigate whether hormonal-neural interactions occur
in the vagina, sixty rats were randomly divided into six groups: Sham-operated,
ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies
were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry.
Results. The density of small nerve fibers was significantly higher in the distal
half areas of intact vaginal walls than the proximal-half areas (P = 0.001). In
contrast, the overall PGP 9.5-ir fiber innervation density was significantly
decreased in the OVX rats subjected to surgical menopause. Sustained estrogen
administration for 2 weeks resulted in nerve fiber proliferation, with values
reaching normal levels in the low-dose estradiol valerate group. Conclusion. Our
findings indicate that systemic hormonal therapy with low-dose estradiol valerate
is effective and safe for treating deficient vaginal innervation caused by low
level of estrogen activity in menopausal women and may aid studies to identify an
optimal estradiol dose to provide relief from vaginal discomfort.
PMID- 28401162
TI - Meta-Analysis of the Relationship between NM23 Expression to Gastric Cancer Risk
and Clinical Features.
AB - The prognostic value of reduced NM23 expression for gastric cancer (GC) patients
is still contradictory. Thus, we conducted a meta-analysis to quantitatively
evaluate the association of NM23 expression with GC risk and clinical features by
analyzing 27 publications. The result of our meta-analysis indicated that NM23
expression is markedly reduced in gastric cancer tissues (OR = 3.15; 95% CI =
1.97-5.03; P < 0.001). Furthermore, NM23 expression was negatively correlated
with N stage, TNM stage, and histological grade. However, NM23 expression was not
correlated with T stage, lymphatic invasion, vascular invasion, and 5-year
overall survival rate. In conclusion, reduced NM23 expression correlated with
gastric cancer risk, but its association with GC clinical features remains
inconclusive. Therefore, large-scale and well-designed studies, which use uniform
antibody and criterion of NM23 positive expression, are required to further
validate the role of the NM23 in predicting GC progression.
PMID- 28401163
TI - Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal Antibody
Mediates Repair of Critical-Size Mandibular Continuity Defects in a Nonhuman
Primate Model.
AB - Antibody-mediated osseous regeneration (AMOR) has been introduced by our research
group as a tissue engineering approach to capture of endogenous growth factors
through the application of specific monoclonal antibodies (mAbs) immobilized on a
scaffold. Specifically, anti-Bone Morphogenetic Protein- (BMP-) 2 mAbs have been
demonstrated to be efficacious in mediating bone repair in a number of bone
defects. The present study sought to investigate the application of AMOR for
repair of mandibular continuity defect in nonhuman primates. Critical-sized
mandibular continuity defects were created in Macaca fascicularis locally
implanted with absorbable collagen sponges (ACS) functionalized with chimeric
anti-BMP-2 mAb or isotype control mAb. 2D and 3D analysis of cone beam computed
tomography (CBCT) imaging demonstrated increased bone density and volume observed
within mandibular continuity defects implanted with collagen scaffolds
functionalized with anti-BMP-2 mAb, compared with isotype-matched control mAb.
Both CBCT imaging and histologic examination demonstrated de novo bone formation
that was in direct apposition to the margins of the resected bone. It is
hypothesized that bone injury may be necessary for AMOR. This is evidenced by de
novo bone formation adjacent to resected bone margins, which may be the source of
endogenous BMPs captured by anti-BMP-2 mAb, in turn mediating bone repair.
PMID- 28401164
TI - Dental Age in Orthodontic Patients with Different Skeletal Patterns.
AB - Objective. To evaluate the difference between chronological and dental age,
calculated by Willems and Cameriere methods, in various skeletal patterns
according to Steiner's ANB Classification. Methods. This retrospective cross
sectional study comprised the sample of 776 participants aged between 7 and 15
years (368 males and 408 females). For each participant, panoramic images (OPT)
and laterolateral cephalograms (LC) were collected from the medical database. On
LC ANB angle was measured; on OPT dental age (DA) was calculated while
chronological age (CA) and sex were recorded. The sample was divided into three
subgroups (Class I, Class II, and Class III) with similar distribution based on
the chronological age and ANB angle. CA was calculated as the difference between
the date of OPT imaging and the date of birth, while DA was evaluated using
Willems and Cameriere methods. ANB angle was measured on LC by two independent
investigators using the cephalometric software. Differences between sexes and the
difference between dental and chronological age were tested by independent and
paired samples t-test, respectively; one-way ANOVA was used to test differences
among ANB classes with Tukey post hoc test to compare specific pairs of ANB
classes. Results. The significant difference was found between Class III and
other two skeletal classes in males using both dental age estimation methods. In
Class III males dental age was ahead averagely by 0.41 years when using Willems
method, while Cameriere method overestimated CA for 0.22 years. Conclusion. In
males with Class III skeletal pattern, dental development is faster than in
Classes I and II skeletal pattern. This faster development is not present in
females.
PMID- 28401165
TI - Evaluation of Mobile Phone and Cordless Phone Use and Glioma Risk Using the
Bradford Hill Viewpoints from 1965 on Association or Causation.
AB - Objective. Bradford Hill's viewpoints from 1965 on association or causation were
used on glioma risk and use of mobile or cordless phones. Methods. All nine
viewpoints were evaluated based on epidemiology and laboratory studies. Results.
Strength: meta-analysis of case-control studies gave odds ratio (OR) = 1.90, 95%
confidence interval (CI) = 1.31-2.76 with highest cumulative exposure.
Consistency: the risk increased with latency, meta-analysis gave in the 10+
years' latency group OR = 1.62, 95% CI = 1.20-2.19. Specificity: increased risk
for glioma was in the temporal lobe. Using meningioma cases as comparison group
still increased the risk. Temporality: highest risk was in the 20+ years' latency
group, OR = 2.01, 95% CI =1.41-2.88, for wireless phones. Biological gradient:
cumulative use of wireless phones increased the risk. Plausibility: animal
studies showed an increased incidence of glioma and malignant schwannoma in rats
exposed to radiofrequency (RF) radiation. There is increased production of
reactive oxygen species (ROS) from RF radiation. Coherence: there is a change in
the natural history of glioma and increasing incidence. Experiment: antioxidants
reduced ROS production from RF radiation. Analogy: there is an increased risk in
subjects exposed to extremely low-frequency electromagnetic fields. Conclusion.
RF radiation should be regarded as a human carcinogen causing glioma.
PMID- 28401166
TI - Hypodontia: An Update on Its Etiology, Classification, and Clinical Management.
AB - Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in
humans. It may occur as part of a recognised genetic syndrome or as a
nonsyndromic isolated trait. Excluding third molars, the reported prevalence of
hypodontia ranges from 1.6 to 6.9%, depending on the population studied. Most
affected individuals lack only one or two teeth, with permanent second premolars
and upper lateral incisors the most likely to be missing. Both environmental and
genetic factors are involved in the aetiology of hypodontia, with the latter
playing a more significant role. Hypodontia individuals often present a
significant clinical challenge for orthodontists because, in a number of cases,
the treatment time is prolonged and the treatment outcome may be compromised.
Hence, the identification of genetic and environmental factors may be
particularly useful in the early prediction of this condition and the development
of prevention strategies and novel treatments in the future.
PMID- 28401167
TI - Glycopatterns of Urinary Protein as New Potential Diagnosis Indicators for
Diabetic Nephropathy.
AB - Diabetic nephropathy is a major cause of chronic kidney disease and end-stage
kidney disease. However, so little is known about alterations of the
glycopatterns in urine with the development of diabetic nephropathy. Presently,
we interrogated glycopatterns in urine specimens using a lectin microarray. The
results showed that expression levels of Siaalpha2-6Gal/GalNAc recognized by SNA
exhibited significantly increased tendency with the development of diabetic
nephropathy; moreover, SNA blotting indicated glycoproteins (90 kDa, 70 kDa, and
40 kDa) in urine may contribute to this alteration. Furthermore, the
glycopatterns of (GlcNAc)2-4 recognized by STL exhibited difference between
diabetic and nondiabetic nephropathy. The results of urinary protein microarray
fabricated by another 48 urine specimens also indicated (GlcNAc)2-4 is a
potential indictor to differentiate the patients with diabetic nephropathy from
nondiabetic nephropathy. Furtherly, STL blotting showed that the 50 kDa
glycoproteins were correlated with this alteration. In conclusion, our data
provide pivotal information to monitor the development of diabetic nephropathy
and distinguish between diabetic nephropathy and nondiabetic renal disease based
on precise alterations of glycopatterns in urinary proteins, but further studies
are needed in this regard.
PMID- 28401168
TI - The Association of a Genetic Variant in SCAF8-CNKSR3 with Diabetic Kidney Disease
and Diabetic Retinopathy in a Chinese Population.
AB - Background. Genome-wide association studies found rs955333 located in 6q25.2 was
associated with diabetic kidney disease in multiple ethnic populations, including
European Americans, African Americans, and Mexican Americans. We aimed to
investigate the association between the variant rs955333 in SCAF8-CNKSR3 and DKD
susceptibility in Chinese type 2 diabetes patients. Methods. The variant rs955333
was genotyped in 1884 Chinese type 2 diabetes patients. Associations of the
variant rs955333 with DKD and DR susceptibility and related quantitative traits
were evaluated. Results. The variant rs955333 was not associated with DKD in our
samples, while subjects with genotype GG were associated with DR (P = 0.047, OR =
0.5525 [0.308,0.9911]), and it also showed association with microalbuminuria (P =
0.024, beta = -0.1812 [-0.339, -0.024]). Conclusion. Our data suggests the
variant rs955333 was not associated with DKD but showed association with diabetic
retinopathy in Chinese type 2 diabetes patients.
PMID- 28401170
TI - Corrigendum to "Hypoglycemic Activity through a Novel Combination of Fruiting
Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes
Mellitus Mice".
AB - [This corrects the article DOI: 10.1155/2015/723190.].
PMID- 28401169
TI - Epigenetic Regulations in Diabetic Nephropathy.
AB - Diabetic nephropathy (DN) is a chronic complication of diabetes and the most
common cause of end-stage kidney disease. It has been reported that multiple
factors are involved in the pathogenesis of DN, while the molecular mechanisms
that lead to DN are still not fully understood. Numerous risk factors for the
development of diabetic nephropathy have been proposed, including ethnicity and
inherited genetic differences. Recently, with the development of high-throughput
technologies, there is emerging evidence that suggests the important role of
epigenetic mechanisms in the pathogenesis of DN. Epigenetic regulations,
including DNA methylation, noncoding RNAs, and histone modifications, play a
pivotal role in DN pathogenesis by a second layer of gene regulation. All these
findings can contribute to developing novel therapies for DN.
PMID- 28401171
TI - Special Section Guest Editorial: Brain Mapping and Therapeutics.
PMID- 28401172
TI - Special Section Guest Editorial: Positron Emission Tomography: History, Current
Status, and Future Prospects.
PMID- 28401174
TI - Estimating scatter from sparsely measured primary signal.
AB - Scatter radiation severely degrades the image quality. Measurement-based scatter
correction methods sample the scatter signal at sparsely distributed points, from
which the scatter profile is estimated and deterministically removed from the
projection image. The estimation of the scatter profile is generally done through
a spline interpolation and the resulting scatter profile is quite smooth.
Consequently, the noise is intact and the signal-to-noise ratio is reduced in the
projection image after scatter correction, leading to image artifacts and
increased noise in the reconstruction images. We propose a simple and effective
method, referred to as filtered scatter-to-primary ratio ([Formula: see text]
SPR) estimation, to estimate the scatter profile using the sparsely sampled
scatter signal. Using the primary sampling device and the stationary digital
tomosynthesis systems previously developed in our lab, we evaluated and compared
the [Formula: see text]-SPR method in comparison with existing methods in terms
of contrast ratio, signal difference-to-noise ratio, and modulation transfer
function. A significant improvement in image quality is observed in both the
projection and the reconstruction images using the proposed method.
PMID- 28401173
TI - History and future technical innovation in positron emission tomography.
AB - Instrumentation for positron emission tomography (PET) imaging has experienced
tremendous improvements in performance over the past 60 years since it was first
conceived as a medical imaging modality. Spatial resolution has improved by a
factor of 10 and sensitivity by a factor of 40 from the early designs in the
1970s to the high-performance scanners of today. Multimodality configurations
have emerged that combine PET with computed tomography (CT) and, more recently,
with MR. Whole-body scans for clinical purposes can now be acquired in under 10
min on a state-of-the-art PET/CT. This paper will review the history of these
technical developments over 40 years and summarize the important clinical
research and healthcare applications that have been made possible by these
technical advances. Some perspectives for the future of this technology will also
be presented that promise to bring about new applications of this imaging
modality in clinical research and healthcare.
PMID- 28401175
TI - Anthropomorphic dual-lattice voxel models for optimizing image quality and dose.
AB - Using numerical simulations, the influence of various imaging parameters on the
resulting image can be determined for various imaging technologies. To achieve
this, visualization of fine tissue structures needed to evaluate the image
quality with different radiation quality and dose is essential. The present work
examines a method that employs simulations of the imaging process using Monte
Carlo methods and a combination of a standard and higher resolution voxel models.
A hybrid model, based on nonlinear uniform rational B-spline and polygon mesh
surfaces, was constructed from an existing voxel model of a female patient of a
resolution in the range of millimeters. The resolution of the hybrid model was
[Formula: see text], i.e., substantially finer than that of the original model.
Furthermore, a high resolution lung voxel model [[Formula: see text] voxel
volume, slice thickness: [Formula: see text]] was developed from the specimen of
a left lung lobe. This has been inserted into the hybrid model, substituting its
left lung lobe and resulting in a dual-lattice geometry model. "Dual lattice"
means, in this context, the combination of voxel models with different
resolutions. Monte Carlo simulations of radiographic imaging were performed and
the fine structure of the lung was easily recognizable.
PMID- 28401176
TI - Evaluation of a projection-domain lung nodule insertion technique in thoracic
computed tomography.
AB - Task-based assessment of computed tomography (CT) image quality requires a large
number of cases with ground truth. Prospective case acquisition can be time
consuming. Inserting lesions into existing cases to simulate positive cases is a
promising alternative. The aim was to evaluate a recently developed projection
based lesion insertion technique in thoracic CT. In total, 32 lung nodules of
various attenuations were segmented from 21 patient cases, forward projected,
inserted into projections, and reconstructed. Two experienced radiologists and
two residents independently evaluated these nodules in two substudies. First, the
32 inserted and the 32 original nodules were presented in a randomized order and
each received a score from 1 to 10 (1 = absolutely artificial to 10 = absolutely
realistic). Second, the inserted and the corresponding original lesions were
presented side-by-side to each reader. For the randomized evaluation,
discrimination of real versus inserted nodules was poor with areas under the
receiver operative characteristic curves being 0.57 [95% confidence interval
(CI): 0.46 to 0.68], 0.69 (95% CI: 0.58 to 0.78), and 0.62 (95% CI: 0.54 to 0.69)
for the two residents, two radiologists, and all four readers, respectively. Our
projection-based lung nodule insertion technique provides a robust method to
artificially generate positive cases that prove to be difficult to differentiate
from real cases.
PMID- 28401177
TI - Autophagic degradation of focal adhesions underlies metastatic cancer
dissemination.
AB - Autophagy inhibition is being evaluated as a novel therapeutic strategy in
multiple tumor types, but little is known about its implications for metastatic
dissemination. We recently reported that autophagic degradation of paxillin
through direct interaction with the autophagy protein LC3B is required for focal
adhesion disassembly, Src-stimulated tumor cell motility, and metastasis.
PMID- 28401178
TI - Targeting the AXL signaling pathway in ovarian cancer.
AB - In a recent publication in Science Signaling, we showed that a Mes molecular
subtype of epithelial ovarian cancer (EOC) harboring epithelial-mesenchymal
transition (EMT) features has a unique signaling network downstream of the
GAS6/AXL pathway. Our finding leads to a potential strategy for treating the Mes
subtype of EOC by targeting AXL.
PMID- 28401179
TI - Role of SEC62 in ER maintenance: A link with ER stress tolerance in SEC62
overexpressing tumors?
AB - Amplification of the candidate oncogene TLOC1/SEC62 in tumors correlates with
reduced patient survival. The recently reported role of SEC62 as an autophagy
receptor that controls endoplasmic reticulum (ER) size and function might open
new scenarios for understanding the phenotypes and treat SEC62high tumors, which
are characterized by high ER stress tolerance.
PMID- 28401180
TI - Uncovering a new cellular origin for acute myeloid leukemia with lineage
plasticity.
AB - Although acute myeloid leukaemia (AML) is assumed to be driven by transformed
haematopoietic stem and progenitor cells, we have described recently a new
pathway leading to AML from T-cell progenitors. Furthermore, we could identify a
subgroup of human AML with gene expression profile suggesting T-lymphoid origin
and potentially novel treatment.
PMID- 28401181
TI - KAT2-mediated PLK4 acetylation contributes to genomic stability by preserving
centrosome number.
AB - We have recently identified the first human lysine (K) acetyltransferase 2A and
2B (called KAT2A/2B; known also as GCN5/PCAF, respectively)-dependent acetylome
and revealed a mechanism by which KAT2A/2B-mediated acetylation of
serine/threonine polo-like kinase 4 (PLK4) maintains correct centrosome number in
human cells, therefore contributing to the maintenance of genome stability.1.
PMID- 28401182
TI - Addressing a weakness of anticancer therapy with mitosis inhibitors: Mitotic
slippage.
AB - Mitosis inhibitors, which include antimicrotubule drugs, are chemotherapy agents
that induce the arrest and apoptosis of mitotic cells. Mitotic slippage, in which
mitotically arrested cells exit mitosis, limits the effectiveness of mitosis
inhibitors. We have discovered that the CRL2ZYG11A/B ubiquitin ligase promotes
mitotic slippage. The combination of antimicrotubule drugs and a CRL2ZYG11A/B
inhibitor prevents mitotic slippage to increase antimitotic efficacy.
PMID- 28401183
TI - Insulin receptor substrate 4 (IRS4) is a constitutive active oncogenic driver
collaborating with HER2 and causing therapeutic resistance.
AB - Insulin receptor substrate 4 (IRS4) belongs to a family of cytoplasmic docking
proteins mediating signals from cell surface receptors to downstream effectors.
While IRS1 and IRS2 mediate signals from an active receptor, we found that IRS4
hyperactivates the phosphatidylinositol phosphate kinase (PI3K)-pathway
independent of upstream signals and is irresponsive to feedback regulation
causing cancer and resistance to human epidermal growth factor receptor 2 (HER2)
targeted therapy.
PMID- 28401184
TI - Functional evidence that progenitor cells near sites of inflammation are
precursors for aggressive prostate cancer.
AB - While chronic inflammation has been causally associated with several epithelial
malignancies, whether it causally contributes to the development of prostate
cancer has remained unclear. We recently reported that progenitor-like
inflammation-associated luminal cells marked by low expression of Cluster of
Differentiation 38 (CD38) can initiate human prostate cancer and predict poor
outcome.
PMID- 28401185
TI - Novel mechanism of PCNA control through acetylation of its sliding surface.
AB - Recent findings revealed a new unexpected regulatory mechanism that controls the
proliferating cell nuclear antigen (PCNA). Multiple positively-charged lysine
residues located on the ring inner surface are neutralized by acetylation and
required for cellular resistance to Desoxyribonucleic acid (DNA) damage. Here, we
summarize the key observations, discuss implications, and perspectives linked to
cancer, as well as challenges for future work.
PMID- 28401186
TI - Caspase-9 swings both ways in the apoptosome.
AB - For nearly 2 decades, investigators have debated whether cysteinyl-aspartate
specific protease 9 (caspase-9) is activated within the apoptotic protease
activating factor 1 (Apaf-1) apoptosome through proximity-induced
homodimerization or through formation of a holoenzyme. Recently, we have
demonstrated that caspase-9 forms (and likely transitions between) both caspase-9
homo- and Apaf-1:caspase-9 heterodimers, each of which plays unique roles in the
recruitment and activation of caspase-9.
PMID- 28401187
TI - The yin yang of sunitinib: One drug, two doses, and multiple outcomes.
AB - Our recent work showed that sunitinib exerts dual effect on cancer cells in
different dose ranges. In clinically relevant doses, cancer cells tolerate
sunitinb cytotoxicity by upregulating pro-survival MCL-1 and activating mTORC1
signaling. Inhibition of MCL-1 or mTORC1 sensitized cancer cells to sunitinib.
Analysis of tissues from patients correlated MCL-1/mTORC1 induction with
resistance to sunitinib.
PMID- 28401189
TI - p53 gain-of-function mutations promote metastasis via ENTPD5 upregulation and
enhanced N-glycoprotein folding.
AB - Mutations in cancer abolish normal tumor suppressive functions of tumor protein
p53 (TP53, best known as p53) and convert it into an oncogene. We recently
reported the identification of ectonucleoside triphosphate diphosphohydrolase 5
(ENTPD5) as a transcriptional target of mutant p53 that enhances folding of N
glycosylated proteins required for cancer cell migration, invasion, and
metastasis.
PMID- 28401188
TI - SAMHD1 is a barrier to antimetabolite-based cancer therapies.
AB - The outcome of acute myelogenous leukemia (AML) therapy depends on the propensity
of leukemic blasts to accumulate ara-CTP, the active triphosphate of cytarabine
(ara-C). We identified sterile alpha motif and HD domain-containing protein 1
(SAMHD1) as an ara-CTPase that protects cancer cells from cytarabine-induced
toxicity. Therefore, we propose targeting SAMHD1 as a strategy to potentiate
cytarabine and possibly other antimetabolite-based therapies.
PMID- 28401190
TI - Multigene profiling of single circulating tumor cells.
AB - Numerous techniques for isolating circulating tumor cells (CTCs) have been
developed. Concurrently, single-cell techniques that can reveal molecular
components of CTCs have become widely available. We discuss how the combination
of isolation and multigene profiling of single CTCs in our platform can
facilitate eventual translation to the clinic.
PMID- 28401191
TI - Inhibition of EZH2 degradation as a novel approach to overcome drug resistance in
acute myeloid leukemia.
AB - The polycomb protein enhancer of zeste homolog 2 (EZH2) may have a dual role in
cancer pathogenesis acting as an oncogene or as a tumor suppressor depending on
the cancer type. We recently demonstrated that proteasomal degradation of EZH2
resulting from cyclin-dependent kinase 1 (CDK1)-induced phosphorylation at
Threonine (T) 487 represents a novel mechanism of drug resistance in acute
myeloid leukemia (AML). Our findings suggest that restoration of EZH2 protein is
a viable approach to overcome therapy resistance in AML.
PMID- 28401192
TI - Evasion of targeted cancer therapy through stem-cell-like reprogramming.
AB - Prostate cancer variants expressing alternative lineage markers appear at relapse
from antiandrogen therapy. We show that loss of the retinoblastoma (RB1) and
tumor protein 53 (TP53) genes drives expression of stem cell reprogramming
factors, lineage plasticity, and antiandrogen resistance. Epigenetic manipulation
restores antiandrogen sensitivity-suggesting an approach for treating lethal
prostate cancers.
PMID- 28401193
TI - Intravascular Treatment of Left Subclavian Artery Aneurysm Coexisting with Aortic
Coarctation in an Adult Patient.
AB - Coexistence of aortic coarctation with aneurysm of subclavian artery is a
uncommon situation and may require unusual treatment in patients. A 40-year-old
patient diagnosed incidentally with left subclavian artery aneurysm coexisting
with aortic coarctation. Patient was initially referred for hybrid treatment.
Initially ostium of the left subclavian artery was covered with a stent-graft.
Over a 30-month follow-up period aneurysm became thrombosed all the way up to the
ostium of internal mammary artery. The patient did not present with neurological
symptoms or signs of upper limb ischemia. Taking into consideration good blood
supply to the axillary artery via reversed blood flow in the thyreocervical
trunk, hence we decided not to proceed with cervicoaxillary bypass grafting.
Implantation stent-graft into aorta coarctation with covering axillary artery is
proper way of treatment and may need no other surgical procedures.
PMID- 28401194
TI - Effect of Electrical Stimulation on Blood Flow Velocity and Vessel Size.
AB - Interferential current electrical stimulation alters blood flow velocity and
vessel size. We aimed to investigate the changes in the autonomic nervous system
depending on electrical stimulation parameters. Forty-five healthy adult male and
female subjects were studied. Bipolar adhesive pad electrodes were used to
stimulate the autonomic nervous system at the thoracic vertebrae 1-4 levels for
20 min. Using Doppler ultrasonography, blood flow was measured to determine
velocity and vessel size before, immediately after, and 30 min after electrical
stimulation. Changes in blood flow velocity were significantly different
immediately and 30 min after stimulation. The interaction between intervention
periods and groups was significantly different between the exercise and pain
stimulation groups immediately after stimulation (p<0.05). The vessel size was
significantly different before and 30 min after stimulation (p<0.05). Imbalances
in the sympathetic nervous system, which regulates balance throughout the body,
may present with various symptoms. Therefore, in the clinical practice, the
parameters of electrical stimulation should be selectively applied in accordance
with various conditions and changes in form.
PMID- 28401195
TI - Live Birth Pregnancy Outcome after First In Vitro Fertilization Treatment in a
Patient with Systemic Lupus Erythematosus and Isolated High Positive IgA Anti
beta2glycoprotein I Antibodies: A Case Report.
AB - IgA anti-beta2glycoprotein I antibodies (IgA-anti-beta2GPI) seems to be the most
prevalent isotype in patients with Systemic Lupus Erythematosus (SLE) with a
significant association to thrombotic events. Both SLE and antiphospholipid
syndrome (APS) can be associated with implantation failure, fetal loss and
obstetric complications. Recent reports highlight the clinical value of IgA-anti
beta2GPI determination in supporting in vitro fertilization (IVF) treatment and
IVF pregnancy outcomes. We report a 36-year-old female diagnosed with SLE,
endometriosis and unexplained infertility. Conventional APS markers were
consistently negative: anti-cardiolipin (aCL) and anti-beta2GPI: IgG/IgM. She was
then tested with reports of repeatedly high IgA-anti-beta2GPI and tested positive
from 2014 after IgA (aCL; anti-beta2GPI) were established in our APS diagnostic
panel. She underwent successful first IVF procedure with a 30 week live birth
pregnancy outcome. During the follow up no lupus flare, thrombosis or ovarian
hyperstimulation syndrome were registered. Serum IgA anti-beta2GPI and anti-dsDNA
levels declined statistically significant during the second and third trimester.
Titres of IgA-anti-beta2GPI remained lower postpartum as well. This case
highlights the clinical importance of IgA-anti-beta2GPI testing for family
planning, assisted reproduction and pregnancy in women with SLE and/or APS.
PMID- 28401196
TI - Periodontal Ligament Stem Cells Regulate Apoptosis of Neutrophils.
AB - Periodontal ligament stem cells (PDLSCs) are promising cell resource for the cell
based therapy for periodontitis and regeneration of bio-root. In this study, we
investigated the effect of PDLSCs on neutrophil, a critical constituent of innate
immunity, and the underlying mechanisms. The effect of PDLSCs on the
proliferation and apoptosis of resting neutrophils and IL-8 activated neutrophils
was tested under cell-cell contact culture and Transwell culture, with or without
anti-IL-6 neutralizing antibody. We found that PDLSCs could promote the
proliferation and reduce the apoptosis of neutrophils whether under cell-cell
contact or Transwell culture. Anti-IL-6 antibody reduced PDLSCs-mediated
inhibition of neutrophil apoptosis. IL-6 at the concentration of 10ng/ml and
20ng/ml could inhibit neutrophil apoptosis statistically. Collectively, PDLSCs
could reduce the apoptosis of neutrophils via IL-6.
PMID- 28401197
TI - Platelet-Rich Fibrin (PRF) in Implants Dentistry in Combination with New Bone
Regenerative Flapless Technique: Evolution of the Technique and Final Results.
AB - : Most common techniques for alveolar bone augmentation are guided bone
regeneration (GBR) and autologous bone grafting. GBR studies demonstrated long
term reabsorption using heterologous bone graft. A general consensus has been
achieved in implant surgery for a minimal amount of 2 mm of healthy bone around
the implant. A current height loss of about 3-4 mm will result in proper deeper
implant insertion when alveolar bone expansion is not planned because of the dome
shape of the alveolar crest. To manage this situation a split crest technique has
been proposed for alveolar bone expansion and the implants' insertion in one
stage surgery. Platelet-rich fibrin (PRF) is a healing biomaterial with a great
potential for bone and soft tissue regeneration without inflammatory reactions,
and may be used alone or in combination with bone grafts, promoting hemostasis,
bone growth, and maturation. AIM: The aim of this study was to demonstrate the
clinical effectiveness of PRF combined with a new split crest flapless modified
technique in 5 patients vs. 5 control patients. MATERIALS AND METHODS: Ten
patients with horizontal alveolar crests deficiency were treated in this study,
divided into 2 groups: Group 1 (test) of 5 patients treated by the flapless split
crest new procedure; Group 2 (control) of 5 patients treated by traditional
technique with deeper insertion of smaller implants without split crest. The
follow-up was performed with x-ray orthopantomography and intraoral radiographs
at T0 (before surgery), T1 (operation time), T2 (3 months) and T3 (6 months) post
operation. RESULTS: All cases were successful; there were no problems at surgery
and post-operative times. All implants succeeded osteointegration and all
patients underwent uneventful prosthetic rehabilitation. Mean height bone loss
was 1 mm, measured as bone-implant most coronal contact (Delta-BIC), and occurred
at immediate T2 post-operative time (3 months). No alveolar bone height loss was
detected at implant insertion time, which was instead identified in the control
group because of deeper implant insertion. CONCLUSION: This modified split crest
technique combined with PRF appears to be reliable, safe, and to improve the
clinical outcome of patients with horizontal alveolar crests deficiency compared
to traditional implanting techniques by avoiding alveolar height-loss related to
deeper insertion of smaller implants.
PMID- 28401198
TI - The Significance of Strong Ion Gap for Predicting Return of Spontaneous
Circulation in Patients with Cardiopulmonary Arrest.
AB - Useful parameters that can predict return of spontaneous circulation (ROSC) in
patients with cardiopulmonary arrest (CPA) have not been established. We
previously reported the usefulness of anion gap (AG) and albumin-corrected anion
gap (ACAG) calculated from a blood sample obtained on arrival at the hospital for
the prediction of ROSC. Otherwise, it has been reported that strong ion gap
(SIG), which shows the difference between the levels of fully dissociated cations
and anions in the serum, is useful to predict the prognosis of critically ill
patients. This was a prospective and observational clinical study. Patients with
CPA transferred to the emergency department of our hospital between January 2013
and December 2014 were evaluated. Patients were divided into two groups: patients
who obtained ROSC [ROSC(+) group] and those who did not [ROSC(-) group]. We
compared AG, ACAG and SIG between the two groups. A total of 170 patients were
enrolled. Fifty patients were included in the ROSC(+) group, and the remaining
120 in the ROSC(-) group. Both AG and ACAG were significantly better in the
ROSC(+) group; however, there was no significant difference in SIG between the
two groups. The area under the receiver operating characteristic curves (AUC) for
ROSC of both AG and ACAG were almost the same (0.72 and 0.708, respectively); the
AUC of SIG (0.57) was inferior to those of AG and ACAG. Our results suggest that
AG and ACAG can better predict ROSC following cardiopulmonary resuscitation (CPR)
compared with SIG.
PMID- 28401199
TI - Clinicopathology of EpCAM and EGFR in Human Epithelial Ovarian Carcinoma.
AB - The objective of this study was to explore the expression of EpCAM and EGFR in
human epithelial ovarian cancer (EOC) and their correlation with
clinicopathological parameters. The protein expression levels of epithelial cell
adhesion molecule (EpCAM) and epidermal growth factor receptor (EGFR) were
evaluated by immunohistochemistry in formalin-fixed paraffin-embedded specimens
from 30 patients with epithelial ovarian carcinoma and 15 normal ovary tissues.
Clinicopathological characteristics were gathered by retrospective review of the
patients' files. The correlation between EpCAM and EGFR expression, as well as
their association with clinical pathological parameters were investigated. The
SPSS 17.0 package was used to perform statistical analyses. The positive
expression rates of EpCAM and EGFR were significantly elevated in epithelial
ovarian cancer tissues than in normal ovary tissues. The positive expressions of
EpCAM and EGFR in EOC were associated with International Federation of Gynecology
and Obstetrics (FIGO) stage and tumor differentiation, lymph node metastasis.
Spearman correlation analysis demonstrated a significant positive association
between EpCAM and EGFR expression in EOC. The co-expression of EpCAM and EGFR may
play an important role in the carcinogenesis of EOC and might provide a promising
molecular therapeutic target.
PMID- 28401200
TI - Intraosseous Lipoma of the Mandibula: A Case Report and Review of the Literature.
AB - Lipoma is a benign tumour originating from mature adipose tissue. It can occur in
any place in the body where adipose tissue is located. Intraosseous lipoma is a
very rare bone tumour. The authors present an infrequent case involving
intraosseous lipoma of the mandible in a 32-year old man and provide a review of
case studies documented earlier in the literature.
PMID- 28401201
TI - A combination strategy using two novel cerium-based nanocomposite affinity probes
for the selective enrichment of mono- and multi-phosphopeptides in mass
spectrometric analysis.
AB - This work presents a sequential enrichment protocol, based on two self-designed
cerium-based nanocomposite affinity probes, which not only can effectively
separate phosphopeptides from non-phosphopeptides but can also selectively
differentiate mono- and multi-phosphopeptides for direct matrix-assisted laser
desorption/ionization time-of-flight mass spectrometric (MALDI-TOF MS) analysis.
PMID- 28401202
TI - Preparation of ordered N-doped mesoporous carbon materials via a polymer-ionic
liquid assembly.
AB - Here we report a facile and effective strategy for the preparation of ordered
mesoporous carbon materials with a high-nitrogen-content (8.1 at%) coating layer
through a polymer-ionic liquid assembly strategy. The prepared N-doped mesoporous
carbon materials demonstrated enhanced CO2 adsorption capacity (2.29 mmol g-1)
compared with non-doped carbon (1.84 mmol g-1).
PMID- 28401203
TI - Development of a wash-free immunoassay using Escherichia coli cells with
autodisplayed Z-domains.
AB - Escherichia coli cells that autodisplay Z-domains have been used to improve the
sensitivity and limit of detection (LOD) of immunoassays by controlling antibody
orientation. In this study, a rapid, wash-free immunoassay was developed using E.
coli cells with autodisplayed Z-domains and flow cytometry. The fluorescence
signal from a single E. coli cell could be identified and background noise from
non-bound detection antibodies was minimal. Flow cytometric measurement was
demonstrated to be more effective than microscopy or fluorescence photometry. The
concentrations of the capture and detection antibodies were optimized by testing
various concentrations; the incubation time was optimized in the same way. The
wash-free immunoassay was used to quantify the C-reactive protein (CRP) and the
results were compared with those of an established assay method. The results of
the wash-free immunoassay were significantly correlated with the results of the
washing method, but showed an improved LOD and dynamic range. Thus, the wash-free
immunoassay based on E. coli cells with autodisplayed Z-domains and flow
cytometry developed here was confirmed to be feasible for use in medical
diagnosis.
PMID- 28401204
TI - Protein self-assembly following in situ expression in artificial and mammalian
cells.
AB - The self-assembly of proteins has been widely studied in controlled in vitro
conditions, and more recently in biological environments. The self-assembly of
proteins in biology can be a feature of the pathogenesis of protein condensation
disease, or can occur during normal physiological function, for example during
the formation of intracellular non-membrane bound organelles. To determine the
mechanisms for the assembly process fully, controlled in vitro experiments using
purified protein solutions are often required. However, making direct connections
between insights gathered from controlled experiments and those in complex
biological environments remains a challenge. Using the P23T mutant of human
gammaD-crystallin, a protein associated with congenital cataract, we have
demonstrated that the equilibrium solubility boundary and solution behavior
measured using phase diagrams of purified protein solutions is consistent with
the assembly of the protein expressed in cell-free expression medium in
artificial cells (without fluorescent labelling) and condensates formed in
mammalian cells, thereby directly connecting in vitro measurements with those
performed under physiological conditions.
PMID- 28401205
TI - One-step colorimetric detection of an antibody based on protein-induced unfolding
of a G-quadruplex switch.
AB - A simple colorimetric assay is developed for the sensitive and selective
detection of an antibody, which combines a protein binding-induced signaling
approach with a novel DNAzyme-based conformational switching strategy.
PMID- 28401206
TI - Recent advances in carbon based nanosystems for cancer theranostics.
AB - One of the major challenges in our contemporary society is to facilitate healthy
life for all human beings. In this context, cancer has become one of the most
deadly diseases around the world, and despite many advances in theranostics
techniques the treatment of cancer still remains an important problem. With
recent advances made in the field of nano-biotechnology, carbon-based
nanostructured materials have drawn special attention because of their unique
physicochemical properties, giving rise to great potential for the diagnosis and
therapy of cancer. This review deals with four different types of carbon
allotrope including carbon nanotubes, graphene, fullerenes and nanodiamonds and
summarizes the results of recent studies that are likely to have implications in
cancer theranostics. We discuss the applications of these carbon allotropes for
cancer imaging and drug delivery, hyperthermia, photodynamic therapy and acoustic
wave assisted theranostics. We focus on the results of different studies
conducted on functionalized/conjugated carbon nanotubes, graphene, fullerenes and
nanodiamond based nanostructured materials reported in the literature in the
current decade. The emphasis has been placed on the synthesis strategies,
structural design, properties and possible mechanisms that are perhaps
responsible for their improved theranostic characteristics. Finally, we discuss
the critical issues that may accelerate the development of carbon-based
nanostructured materials for application in cancer theranostics.
PMID- 28401207
TI - Highly active Fe3BO6 as an anode material for sodium-ion batteries.
AB - A highly efficient Fe3BO6 anode prepared via a solid-state synthesis method is
studied for sodium-ion batteries. The Fe3BO6 anode shows high capacity and
excellent rate capability. The ex situ X-ray diffraction results show that the
Na+ ion storage mechanism involves conversion based reactions between iron oxides
and sodium.
PMID- 28401208
TI - Asymmetric [3+2] cycloaddition of 3-amino oxindole-based azomethine ylides with
alpha,beta-ynones: a straightforward approach to spirooxindoles incorporating 2,5
dihydropyrroles and pyrroles.
AB - An organocatalytic asymmetric [3+2] cycloaddition of 3-amino oxindole-based
azomethine ylides and alpha,beta-ynones has been developed. This reaction
afforded spiro[dihydropyrrole-2,3'-oxindole] products in high chemical yields
with excellent stereoselectivities (up to 99% yields, >20 : 1 dr and >99% ee).
Notably, a series of important spiro[pyrrole-oxindole] derivatives were readily
obtained via oxidation of the cycloadducts, thus extending the diversity of the
products.
PMID- 28401209
TI - Unusual molecular mechanism behind the thermal response of polypeptoids in
aqueous solutions.
AB - Poly(alpha-peptoid)s, a structural isomer to polypeptides, have recently
attracted a significant amount of scientific attention. However, the molecular
mechanism behind the thermal response of this class of polymers is unknown. Here,
the thermal response of two polypeptoids in aqueous solutions was studied by
different methodologies, including dynamic light scattering, IR spectroscopies,
NMR, etc. Our studies focused on two polypeptoids with identical alkyl side chain
compositions, but different architecture; i.e., cyclic and linear. Aqueous
solutions of the cyclic and linear polymers present phase transition temperatures
at 43 degrees C and 47 degrees C, respectively, that have an anomalous
dependence on the polymer morphology as expected from macromolecules having very
similar solvent interactions, but different conformational entropy. The atypical
trend in the phase transition temperature is found to be caused by the initiator
required in the synthesis which favors the formation of soluble dimers in the
cyclic polymer. Our experimental findings also demonstrate that the phase
transition, irrespective of the morphology, is governed by the polymer backbone
conformation which depends on the composition and structure of the alkyl side
chains. This proposed mechanism is novel and different from the commonly assumed
mechanism for thermo-responsive polymers in which the hydration of the polymer
cause by a coil to globule transition is the determining factor. Moreover, the
proposed mechanism is likely to be general since it can explain not only the
experimental findings of this work, but also observations of the thermal response
and conformation of other studied polypeptoids in water. Finally, our mechanism
gives a molecular framework for the rational designed of polypeptoids with
tailored phase transition temperatures.
PMID- 28401210
TI - Mastering the magnetic susceptibility of magnetically responsive bicelles with
3beta-amino-5-cholestene and complexed lanthanide ions.
AB - The magnetic susceptibility of lanthanide-chelating bicelles was selectively
enhanced by introducing 3beta-amino-5-cholestene (aminocholesterol, Chol-NH2) in
the bilayer. Unprecedented magnetic alignment of the bicelles was achieved
without altering their size. An aminocholesterol conjugate (Chol-C2OC2-NH2), in
combination with different lanthanide ions, offers the possibility of fine-tuning
the bicelle's magnetic susceptibility.
PMID- 28401211
TI - Single-molecule imaging of telomerase activity via linear plasmon rulers.
AB - Plasmon rulers (PRs) exploit the potential of plasmon coupling between individual
pairs of noble metal nanoparticles in biological processes, especially single
molecule detection. Herein, for the first time, we report a strategy based on Ag
PRs for in situ monitoring of the extension process of telomerase primer (TSP)
activated by a single telomerase.
PMID- 28401212
TI - Filler flocculation in polymers - a simplified model derived from thermodynamics
and game theory.
AB - The performance of elastomeric materials, i.e. in car tires, is substantially
determined by the used reinforcing filler system. In particular, the flocculation
tendency of filler particles to form clusters and even network-like structures
significantly determines the mechanical properties of these elastomer materials
and enhances especially their energy dissipation under periodic mechanical
deformations. In a simplified thermodynamic model, inspired by a segregation
model from game theory, we describe fundamental mechanisms of filler structure
formation. As the final goal of this paper we want to demonstrate how similar
structures in society, nature or materials like rubbers emerge when supposing
obvious cardinal mechanisms of structure formation in complex systems.
PMID- 28401213
TI - An organolanthanide(iii) single-molecule magnet with an axial crystal-field:
influence of the Raman process over the slow relaxation.
AB - Here, we report the synthesis and magnetic properties investigation of a series
of new organometallic homoleptic complexes Li(DME)3[Ln(DAD)2] (Ln = Dy (1a, 1b),
Tb(2), and Er(3)) based on paramagnetic Ln(iii) ions coordinated by an ene
diamido[2,6-iPr2C6H3N-CH[double bond, length as m-dash]CH-NC6H3iPr2-2,6]2- (DAD)
ligand. Dy-based compounds exhibit a genuine single-molecule magnet (SMM)
behaviour, while the Tb3+ analogue shows a field-induced slow relaxation of the
magnetisation.
PMID- 28401214
TI - Chemo-enzymatic synthesis of equisetin.
AB - We here report that the biosynthesis of equisetin, a fungal tetramate natural
product with potent anti-infectious activity, relies on Fsa2, a Diels-Alderase
that constructs the trans-decalin system of the molecule in a stereo-selective
manner. This finding led to the development of a concise chemo-enzymatic route
toward the synthesis of equisetin, which involves facile preparation of a linear
polyene precursor via 7-steps and Fsa2 activity for equisetin maturation through
an intramolecular Diels-Alder reaction, thus exemplifying the significance of the
combination of chemical and biological methods to achieve structurally complex
cyclic natural products and their derivatives.
PMID- 28401215
TI - Prebiotic synthesis of aminooxazoline-5'-phosphates in water by oxidative
phosphorylation.
AB - RNA is essential to all life on Earth and is the leading candidate for the first
biopolymer of life. Aminooxazolines have recently emerged as key prebiotic
ribonucleotide precursors, and here we develop a novel strategy for
aminooxazoline-5'-phosphate synthesis in water from prebiotic feedstocks.
Oxidation of acrolein delivers glycidaldehyde (90%), which directs a
regioselective phosphorylation in water and specifically affords 5'
phosphorylated nucleotide precursors in upto 36% yield. We also demonstrated a
generational link between proteinogenic amino acids (Met, Glu, Gln) and
nucleotide synthesis.
PMID- 28401216
TI - Effects of vertical confinement on gelation and sedimentation of colloids.
AB - We consider the sedimentation of a colloidal gel under confinement in the
direction of gravity. The confinement allows us to compare directly experiments
and computer simulations, for the same system size in the vertical direction. The
confinement also leads to qualitatively different behaviour compared to bulk
systems: in large systems gelation suppresses sedimentation, but for small
systems sedimentation is enhanced relative to non-gelling suspensions, although
the rate of sedimentation is reduced when the strength of the attraction between
the colloids is strong. We map interaction parameters between a model
experimental system (observed in real space) and computer simulations.
Remarkably, we find that when simulating the system using Brownian dynamics in
which hydrodynamic interactions between the particles are neglected, we find that
sedimentation occurs on the same timescale as the experiments. An analysis of
local structure in the simulations showed similar behaviour to gelation in the
absence of gravity.
PMID- 28401218
TI - Dual pO2/pCO2 fibre optic sensing film.
AB - A fibre optic multi-sensor has been developed for biomedical sensing applications
using a tip coating solution sensitive to both oxygen and carbon dioxide. An
oxygen sensitive phosphorescence quenching complex based on platinum
octaethylporphyrin (PtOEP) was combined with a carbon dioxide sensitive
phosphorescence compound based on 8-hydroxypyrene-1,3,6-trisulfonic acid
trisodium salt (HPTS). When excited by blue light (470 nm), the resultant coating
had two fluorescent peaks at 515 nm (green) and 645 nm (red) which responded to
partial pressure of CO2 and O2 respectively. The sensor was tested in vitro and
shown to be able to measure CO2 and O2 simultaneously and in real time, with
calibration constants of 0.0384 kPa-1 and 0.309 kPa-1 respectively. The O2
sensitive peak received some overlap from the 515 nm peak (0.38% of peak
intensity) as well as some cross-sensitivity (maximum, 5.1 kPa pCO2 gave a
measurement equivalent to 0.43 kPa of O2, a ratio of 0.08 : 1). However, these
effects can be subtracted from measurements and no significant cross-sensitivity
or overlap was seen in CO2 measurements from O2. This novel compound presents
great potential for use in medical sensors and we expect it to be important to a
wide range of future applications.
PMID- 28401219
TI - Rhodium-catalyzed intermolecular [3+3] cycloaddition of vinyl aziridines with C,N
cyclic azomethine imines: stereospecific synthesis of chiral fused tricyclic
1,2,4-hexahydrotriazines.
AB - An atom-economic route to ring-fused 1,2,4-hexahydrotriazines relying upon a new
synthetic application of vinylaziridines in a rhodium-catalyzed intermolecular
[3+3] cycloaddition of C,N-cyclic azomethine imines has been reported. Highly
efficient chirality transfer in the present transformation was also observed,
providing a new method for the synthesis of sp3-carbon-rich 1,2,4
hexahydrotriazines in an enantioselective manner.
PMID- 28401217
TI - Activation of autophagy by elevated reactive oxygen species rather than released
silver ions promotes cytotoxicity of polyvinylpyrrolidone-coated silver
nanoparticles in hematopoietic cells.
AB - Silver nanoparticles (AgNPs) are the most commonly used engineered nanomaterials
in commercialized products because of their antimicrobial activity. Previously,
we have shown that polyvinylpyrrolidone (PVP)-coated AgNPs have an anti-leukemia
effect against human myeloid leukemia cells; however, whether AgNPs are able to
trigger autophagy in normal hematopoietic cells and the role of autophagy in AgNP
induced cytotoxicity remain unclear. In the current study, we observed that AgNPs
were taken up by murine pro-B cells (Ba/F3), and then promoted accumulation of
autophagosomes, which resulted from the induction of autophagy rather than the
blockade of autophagic flux. AgNPs induced cytotoxicity in a dose-dependent
manner accompanied by apoptosis and DNA damage through the production of reactive
oxygen species (ROS) and the release of silver ions. The ROS-mediated mTOR
signaling pathway was responsible for the induction of autophagy. More
importantly, the inhibition of autophagy with the addition of 3-methyladenine (3
MA) or silencing of Atg5 significantly attenuated the cytotoxicity of AgNPs in
Ba/F3. These findings suggest that autophagy is involved in the cytotoxicity of
PVP-coated AgNPs in normal hematopoietic cells, and the inhibition of autophagy
is a novel and potent strategy to protect normal hematopoietic cells upon
treatment with AgNPs.
PMID- 28401220
TI - Polyoxotungstate incorporating organotriphosphonate ligands and lanthanide ions:
syntheses, characterization, magnetism and photoluminescence properties.
AB - Four structurally intriguing members of a new family of lanthanide (Ln)
containing organophosphonate-functionalized polyoxotungstates with the general
formula K2[Ln(H2O)4(AsW9O33)(W2O3)(O3PCOHCH3PO3)Ln(H2O)7]2.15H2O [Ln = Ce (1Ce),
Nd (2Nd), Sm (3Sm) and Eu (4Eu)] were directly isolated by controlling the
reaction parameters and well established by single-crystal X-ray diffraction,
PXRD analyses, IR spectra, elemental analyses, TG and EDX analyses. All the four
three-dimensional frameworks consist of the S-shaped inorganic building block
{[(AsW9O33)(W2O3)]2}, two organophosphonate groups {O3PCOHCH3PO3} and four Ln
ions. The magnetic properties of the four compounds and the solid-state
photoluminescence properties of 2Nd, 3Sm, and 4Eu were also fully investigated.
PMID- 28401221
TI - Synthesis of two titanosilicates with distinct interlayer connections from
similar gels.
AB - Ti-SSZ-70 and Ti-ECNU-6, with identical intralayer structures but distinct
interlayer connections, were prepared from similar synthetic gels free of alkali
metal ions and boric acid. Ti-SSZ-70, composed of vertically misaligned MWW
layers, was transferred to Ti-ECNU-6, structurally analogous to the Ti-MWW
zeolite with a well-aligned layer stacking, upon the addition of an appropriate
amount of hexamethyleneimine to the gel. These two titanosilicate catalysts
exhibited outstanding catalytic activities in the liquid-phase alkene
epoxidation.
PMID- 28401222
TI - Co-organizing synthesis of heterogeneous nanostructures through the photo
cleavage of pre-stabilized self-assemblies.
AB - We devised a co-organizing synthesis by targeting metastable assemblies. Applying
a photo-cleavage reaction to the pre-stabilized self-assembled nanostructures, we
could successfully place physical constraints on the initiating stage of the
molecular co-assembly (CA) process for exotic nanostructures that are away from
the thermodynamic minima.
PMID- 28401223
TI - Transformation of PbI2, PbBr2 and PbCl2 salts into MAPbBr3 perovskite by halide
exchange as an effective method for recombination reduction.
AB - Halide perovskite derivatives present unprecedented physical phenomena among
those materials which are suitable for photovoltaics, such as a fast ion
diffusion coefficient. In this paper it is reported how the benefits of this
property can be used during the growth of halide perovskites in order to control
the morphological and optoelectronic properties of the final thin film. Using a
large enough halide reservoir, the nature of the halides present in the final
perovskite layer can be exchanged and this depends on the initial salt used in
the two-step deposition method. In particular, the preparation of a
methylammonium lead bromide (MAPbBr3) thin film is reported, using a two-step
method based on the transformation of lead(ii) iodide (PbI2), lead(ii) bromide
(PbBr2) and lead(ii) chloride (PbCl2) salts into MAPbBr3 perovskite after dipping
in a methylammonium bromide (MABr) solution. The films prepared from different
salts present different properties in terms of morphology and optoelectronic
properties, thus providing significantly different performance when they are used
for the preparation of photovoltaic devices. Interestingly, the use of PbI2 and
PbCl2 salts reduce the charge recombination and increase the open circuit
potential obtained, especially in the former case. However, the highest
photocurrent is obtained when PbBr2 is used. For PbI2 and PbCl2 salts no traces
of the former salt are observed in the MAPbBr3 layer obtained after 10 minutes of
dipping time, however, the presence of PbBr2 has still been detected (using X-ray
diffraction) when this salt has been employed.
PMID- 28401224
TI - Effect of ion-ligand binding on ion pairing dynamics studied by two-dimensional
infrared spectroscopy.
AB - Cation-specific ion pairing dynamics between M+ (M = Ag or Cu) and SCN- in N,N
dimethylthioformamide (DMTF) are studied by probing the nitrile (CN) stretching
vibration. The SCN- ion, which is an ambidentate ligand, readily associates with
cations to form two different types of contact ion pairs (CIPs) (i.e., M-SCN or M
NCS) and its CN stretching frequency is significantly blue-shifted so that free
SCN- and CIPs can be well-distinguished in the FTIR spectra. Interestingly, Ag+
ions prefer the formation of Ag-SCN in DMTF (Ag+ + SCN- ? Ag-SCN) but Cu+ ions
form Cu-NCS (Cu+ + SCN- ? Cu-NCS). We have studied the effect of ion-ligand
binding on the ion pairing equilibria and dynamics in great detail by using FTIR,
IR pump-probe (IR PP), and two-dimensional infrared (2DIR) spectroscopy combined
with quantum chemical calculations. First, our quantum chemical calculations
corroborate that Ag-SCN and Cu-NCS of the two possible CIP configurations (M-SCN
or M-NCS) are energetically stable and favored in DMTF. Second, the thermodynamic
properties (DeltaH and DeltaS) of ion pairing equilibria are determined by
temperature-dependent FTIR experiments. Finally, IR PP and 2DIR experiments are
used to measure the association and dissociation rate constants. The ion pairing
dynamics between Cu+ and SCN- are found to occur on much faster timescales than
those between Ag+ and SCN-. Our current results provide important insights into
understanding the effect of ion-ligand binding on the ion pairing equilibria and
dynamics in polar solvents.
PMID- 28401225
TI - New insights into the molecular mechanism of Boletus edulis ribonucleic acid
fraction (BE3) concerning antiproliferative activity on human colon cancer cells.
AB - One of the relatively new and promising strategies of cancer treatment is
chemoprevention, which involves the use of natural or synthetic compounds to
block, inhibit or reverse carcinogenesis. A valuable and still untapped source of
chemopreventive compounds seems to be edible mushrooms belonging to higher
Basidiomycetes. Boletus edulis biopolymers extracted with hot water and purified
by anion-exchange chromatography showed antiproliferative activity in colon
cancer cells, but only fraction BE3, mostly composed of ribonucleic acids, was
able to inhibit DNA synthesis in HT-29 cells. The present work aims to elucidate
the molecular mechanism of this Boletus edulis ribonucleic acid fraction and in
this sense flow cytometry and western blotting were applied to cell cycle
analysis in HT-29 cells. We found that the antiproliferative ability of fraction
BE3 observed in HT-29 cells was associated with the modulation of expression of
cell cycle regulatory proteins (Cyclin D1, Cyclin A, p21 and p27) leading to cell
accumulation in the S phase of the cell cycle. Furthermore, the BE3 fraction
showed effective silencing of the signal transduction in an MAPK/Erk pathway in
HT-29 and LS180 colon cancer cell lines. Thus, the previously and currently
obtained results indicate that the BE3 fraction from Boletus edulis has great
potential and needs to be further exploited through animal and clinical studies
in order to develop a new efficient and safe therapeutic strategy for people who
have been threatened by or suffered from colon cancer.
PMID- 28401226
TI - The charge transfer limit of a chemical adduct: the role of perturbation on
external potential.
AB - Full profiles of the components (positive and negative) of density functional
reactivity theory (DFRT) based stabilization energy with respect to the amount of
charge transfer (DeltaN) are investigated on three different Diels-Alder pairs
and twelve different charge transfer complexes formed by BH3-NH3 and their
derivatives. One interesting observation is that the stabilization energy is zero
when the charge transfer (DeltaN) is either zero (lower limit, L.L.) or two times
(higher limit, H.L.) the charge transfer at equilibrium (i.e., when chemical
potentials are equalized). However, the existence of zero stabilization energy at
the zero charge transfer limit is counter-argued after the inclusion of first and
second order effects (due to a perturbing external potential of the partner of a
given atom-in-a-molecule) in the individual energy components as well as the
overall stabilization energy expressions. It has been shown that even when DeltaN
is zero (the lower limit), the net energy change is negative (i.e., the combined
system is stabilized), highlighting the role of non-bonding interactions, rather
than charge-transfer, in stabilizing the combined system at the initial stage of
adduct formation. The higher limit (H.L.) of charge transfer is also shifted to a
much lower value due to the inclusion of this external potential perturbation.
PMID- 28401227
TI - In situ mRNA isolation from a microfluidic single-cell array using an external
AFM nanoprobe.
AB - We present an in situ mRNA extraction platform to quantify marker-genes'
expression levels of single target cells within high-density microfluidic
trapping arrays. This platform enables single-cell transcriptomic analysis to
reveal in-depth information of cellular mechanisms and population heterogeneity.
Although microfluidic technology enables the automation of single-cell sorting,
trapping and identification, most developed microfluidic devices are closed off
and prevent single-cell access by external analytical equipment. Besides, cell
lysing is usually required for mRNA extraction. In our platform, cells are
trapped individually in a microwell array sealed by a 1 MUm-thick
polydimethylsiloxane (PDMS) membrane, and a modified atomic force microscopy
(AFM) probe-a dielectrophoretic nanotweezer (DENT)-penetrates through the
membrane and extracts mRNA molecules from a single cell by dielectrophoresis. The
single-cellular expression levels of 3 housekeeping genes from HeLa cells were
analyzed quantitatively based on the quantification of the extracted mRNAs, and
the probed cells remained viable when the applied alternating-current (AC)
voltage was lower than 1.5 Vpp during mRNA probing. We also performed in situ
mRNA isolation from a mixture of SK-BR-3 and U937 cells, mimicking a blood sample
that underwent primary enrichment of circulating tumor cells (CTCs), and
evaluated various marker-genes' expressions. This integrated platform combines
the non-destructive and precise-control of a single-cell mRNA probe with sealed
microfluidic systems' capability of upstream sample processing and downstream
multifunctional analysis to enable a versatile and powerful tool for biomedical
research.
PMID- 28401228
TI - Environmental photochemistry of fenamate NSAIDs and their radical intermediates.
AB - Fenamates are a class of nonsteroidal anti-inflammatory drugs (NSAIDs) that are
not fully removed during wastewater treatment and can be released to surface
waters. Here, near-surface photochemical half-lives were evaluated to range from
minutes to hours of four fenamates and the closely related diclofenac. While
quantum yields for direct photochemical reactions at the water surface vary
widely from 0.071 for diclofenac to <0.001 for mefenamic acid, all fenamates
showed significant reactivity towards singlet oxygen and hydroxyl radical with
bimolecular reaction rate constants of 1.3-2.8 * 107 M-1 s-1 and 1.1-2.7 * 1010 M
1 s-1, respectively. Photodecay rates increased in the presence of dissolved
organic matter (DOM) for diclofenac (+19%), tolfenamic acid (+9%), and mefenamic
acid (+95%), but decreased for flufenamic acid (-2%) and meclofenamic acid (-14%)
after accounting for light screening effects. Fast reaction rate constants of all
NSAIDs with model triplet sensitizers were quantified by laser flash photolysis.
Here, the direct observation of diphenylamine radical intermediates by transient
absorption spectroscopy demonstrates one-electron oxidation of all fenamates.
Quenching rate constants of these radical intermediates by ascorbic acid, a model
antioxidant, were also quantified. These observations suggest that the balance of
oxidation by photoexcited triplet DOM and quenching of the formed radical
intermediates by antioxidant moieties determines whether net sensitization or net
quenching by DOM occurs in the photochemical degradation of fenamates.
PMID- 28401229
TI - Microengineered biomimetic ocular models for ophthalmological drug development.
AB - Current ophthalmological drug discovery and testing methods have limitations and
concerns regarding reliability, ethicality, and applicability. These drawbacks
can be mitigated by developing biomimetic eye models through mathematical and
experimental methods which are often referred to as "eye-on-a-chip" or "eye
chip". These eye chip technologies emulate ocular physiology, anatomy, and
microenvironmental conditions. Such models enable understanding of the
fundamental biology, pharmacology, and toxicology mechanisms by investigating the
pharmacokinetics and pharmacodynamics of various candidate drugs under ocular
anatomical and physiological conditions without animal models. This review
provides a comprehensive overview of the latest advances in theoretical and in
vitro experimental models of the anterior segment of the eye and its
microenvironment, including eye motions and tear film dynamics. The current state
of ocular modeling and simulation from predictive models to experimental models
is discussed in detail with their advantages and limitations. The potential for
future eye chip models to expedite new ophthalmic drug discoveries is also
discussed.
PMID- 28401230
TI - Synthesis of layer-like Ni(OH)2 decorated ZnIn2S4 sub-microspheres with enhanced
visible-light photocatalytic hydrogen production activity.
AB - Novel layer-like Ni(OH)2 co-catalyst-decorated ZnIn2S4 microsphere photocatalysts
were synthesized for the first time via a facile in situ deposition method to
boost the photocatalytic H2-production performance. The physical and optical
properties of the as-prepared Ni(OH)2-ZnIn2S4 composite samples were
characterized via X-ray diffraction (XRD), transmission electron microscopy
(TEM), UV-vis diffusion reflectance spectroscopy (DRS), X-ray photoelectron
spectroscopy (XPS), and surface photovoltage spectroscopy (SPV). The results
indicate that the photocatalytic H2 evolution activity of the ZnIn2S4
microspheres under visible light irradiation significantly enhances by
introducing inexpensive Ni(OH)2 as a co-catalyst. The 5 mol% Ni(OH)2-ZnIn2S4
sample shows the highest H2-production rate of 8.35 mmol g-1 h-1, which is 18
times higher than that of pure ZnIn2S4. Moreover, photocatalytic activity of the
Ni(OH)2-ZnIn2S4 sample remains stable even after 4 cycling photocatalytic
experiments. In addition, a possible mechanism on the enhanced photocatalytic
activity was proposed and verified by surface photovoltage spectroscopy.
PMID- 28401231
TI - Diverse morphologies in thin-film bijels by varying film thickness and
composition.
AB - Thin-film bijels have many potential energy and environmental applications. In
this work, the metastable bijel morphology space in thin-film confinement is
explored with a Cahn-Hilliard/Brownian-Dynamics computational model. The key
parameters varied are the bijel liquid phase blend ratio and the bijel film
thickness. Simulations reveal a broad spectrum of structurally unique
morphologies that have yet to be observed in experiments and which could have
interesting applications in membrane science and other domains. Extensive
analyses of surface-to-volume ratios, interfacial particle attachment statistics,
and topological interfacial curvatures within the bijels are presented for a
complete characterization of the morphological structure.
PMID- 28401232
TI - Formation of porous nitrogen-doped carbon-coating MnO nanospheres for advanced
reversible lithium storage.
AB - Herein, we have developed a facile and effective approach for synthesizing a
novel kind of porous nitrogen-doped carbon-coated MnO nanosphere. The porous
Mn2O3 nanospheres are initially obtained by the calcination treatment of a
coordination self-assembled aggregation precursor (referred to as Mn(OAc)2-C-8).
Then, MnO@N-doped carbon composites (MnO@NCs) are obtained by the calcination of
the Mn2O3 nanospheres coated with polydopamine (Mn2O3@PDA). The MnO@NCs are
evaluated as an anode for lithium ion batteries (LIBs), which exhibit high
specific capacity, stable cycling performance (1096.6 mA h g-1 after 100 cycles
at 100 mA g-1) and high coulombic efficiency (about 99% over 100 cycles). The
unique structure design and synergistic effect not only settle the challenges of
low conductivity and poor cycling stability of transition metal oxides but also
resolve the imperfection of inferior specific capacity of traditional graphite
materials. Importantly, it may provide a commendable conception for developing
new-fashioned anode materials to improve the lithium storage capability and
electrochemical performance.
PMID- 28401233
TI - Recent progress in transition-metal-catalyzed enantioselective indole
functionalizations.
AB - Numerous efficient synthetic methods for enantioselective indole
functionalizations have emerged in recent years. This review summarizes the major
achievements in the transition-metal-catalyzed enantioselective indole
functionalization reactions since 2010 and focuses on C-C bond formation
processes, including alkylations, arylations, cycloaddition reactions, and other
reactions. It intends to give a compendious overview of the significant progress
achieved in this area.
PMID- 28401234
TI - The effects of Lycium barbarum L. (L. barbarum) on cardiometabolic risk factors:
a meta-analysis of randomized controlled trials.
AB - The effects of Lycium barbarum L. (L. barbarum) on the cardiometabolic risk
factors from randomized controlled trials (RCTs) have shown inconsistent results.
The present meta-analysis aimed to investigate the effects of L. barbarum
supplementation on the cardiometabolic risk factors. A systematic literature
search was performed in Chinese National Knowledge Infrastructure (CNKI), PubMed,
Scopus, and Wanfang databases updated to March 2017. The mean changes in
cardiometabolic risk factors were calculated as the weighted mean difference
(WMD) using a random-effects model. Seven RCTs with a total of 548 subjects were
included. The pooled estimate showed that L. barbarum intervention significantly
reduced the fasting glucose concentrations (-0.36 mmol L-1/-6.5 mg dL-1; 95%
confident interval (CI): -0.62, -0.10 mmol L-1/-11.3, -1.8 mg dL-1). In addition,
L. barbarum supplementation marginally reduced the concentrations of total
cholesterol (TC) (-0.30 mmol L-1/-11.6 mg dL-1; 95% CI: -0.75, 0.15 mmol L-1/
29.0, 5.8 mg dL-1; P = 0.189) and triglyceride (TG) (-0.20 mmol L-1/-17.7 mg dL
1; 95% CI: -0.46, 0.05 mmol L-1/-40.7, 4.4 mg dL-1; P = 0.122), but the summary
estimates did not reach statistical significance. No benefit was found in
relation to bodyweight and blood pressure. The present meta-analysis provides
some evidence that supplemental L. barbarum might have favourable effect on
glucose control.
PMID- 28401235
TI - Efficient construction of C-N and C-S bonds in 2-iminothiazoles via cascade
reaction of enaminones with potassium thiocyanate.
AB - A novel and highly efficient protocol has been developed for the regioselective
synthesis of 2-iminothiazole derivatives with potential biochemical interest by
the reaction of enaminones, potassium thiocyanate (KSCN), and N-bromo succinimide
(NBS) under mild conditions. The reaction proceeds via the formation of alpha
bromo enaminones as a versatile intermediate followed by
thiocyanation/intramolecular cyclization in a one pot manner. The developed
method is particularly attractive due to various advantages including operational
simplicity, mild conditions, being catalyst free, and high bond-forming
efficiency. The proposed protocol explores the synthetic routes of thiazoles by
using various functional enaminones.
PMID- 28401236
TI - An unconventional outer-to-inner synthesis strategy for core (Au)-shell
nanostructures with photo-electrochemical enhancement.
AB - In this work, an outer-to-inner strategy is demonstrated to simultaneously
fabricate core-shell NPs and assemble them onto a scaffold. Specifically, the
shell material is deposited onto the scaffold first, and then a layer of the core
material (Au) is covered on the shell surface. Finally, the core (Au)-shell
nanoparticles (NPs) are formed on the scaffold after annealing. As examples, Au
Bi2S3, Au-CdS and Au-CdSe core-shell NPs are grown on the surface of ZnO nanorods
(NRs) via this strategy and exhibit enhanced photoelectrochemical (PEC)
efficiency. The enhanced PEC performance is ascribed to improved light absorption
induced by the plasmonic effect, trapped electrons of Au NPs, and cascade band
alignment of the shell material and ZnO. The synthetic method gives a universal
route to the development of nanodevices with assembled core-shell NPs. The core
shell NPs in the current study possess significant potential as building blocks
for future PEC anodes or other solar conversion systems.
PMID- 28401237
TI - Large optical Stark shifts in single quantum dots coupled to core-shell
GaAs/AlGaAs nanowires.
AB - Nanowire quantum dots (NW-QDs) can be used for future compact and efficient
optoelectronic devices. Many efforts have been made to control the QD states by
inserting the QDs in doped structures and applying an electric field in a
nanowire system. In this paper, we use down-conversion and up-conversion
photoluminescence excitations to explore the optical and electronic properties of
single quantum dots in GaAs/AlGaAs core-shell nanowires. We investigate a large
optical Stark shift in this system as a new method to tune the QD states. When
the tunable laser lies within the spectral bandwidth of ZB/WZ GaAs (780 nm-860
nm), we observe an extremely large optical Stark shift of 1.3 nm (0.5 nm) with
increasing excitation power at a resonant wavelength of 800 nm (840 nm) in GaAs
states. The ability to in situ control the energy states of self-catalyzed NW-QDs
should open a new way for quantum light sources and nonlinear optics in a
nanowire system.
PMID- 28401238
TI - Voltage-polarity dependent multi-mode resistive switching on sputtered MgO
nanostructures.
AB - Resistive switching in metal-insulator-metal nanosctructures is being intensively
studied for nonvolatile memory applications. Here, we report unipolar resistive
switching in Pt/MgO/Ta/Ru structures, with a 30 nm oxide barrier. A forming
process was needed to initiate the resistive switching, which was then observed
for all Set and Reset voltage polarity combinations. We studied the influence of
the voltage polarity on the variability of the Set/Reset voltages and ON/OFF
resistances and revealed the importance of a thin TaOx layer working as an oxygen
revervoir for resistive switching. The mechanism behind this phenomenon can be
understood in terms of conductive filaments formation/rupture with a contribution
from Joule heating. Resistance change is thus caused by a voltage-driven oxygen
vacancy motion in the MgO layer and a filament model was proposed for each
polarity mode. A OFF/ON resistance ratio of at least 2 orders of magnitude was
obtained with resistive states stable up to 104 s. Our results open the prospect
to improve switching performance in other resistive switching systems, by proving
a better understanding of the differences between operation modes.
PMID- 28401239
TI - From oxidative degradation to direct oxidation: size regimes in the consecutive
reaction of cationic tantalum clusters with dioxygen.
AB - Cationic tantalum clusters (Ta9-12+) are reacted with molecular oxygen under
multi-collision conditions in the gas phase in order to analyze the reaction
kinetics. Clusters in this transitional size regime demonstrate reaction pathways
associated with smaller clusters that mainly degrade upon oxidation (loss of a
TaO unit) and those of larger clusters that are oxidized in absence of
fragmentation. This behavior is exemplified by Ta9+, which generates Ta9O14+ and
Ta4O11+, and the underlying, intricate reaction network is subsequently
investigated. Ultimately, rate constants, reaction pathways and final products of
cluster sizes up to n = 40 are compared to reveal the size-dependent oxidation
behavior.
PMID- 28401240
TI - Correction: The aromaticity of dicupra[10]annulenes.
AB - Correction for 'The aromaticity of dicupra[10]annulenes' by Rafael Grande-Aztatzi
et al., Phys. Chem. Chem. Phys., 2017, 19, 9669-9675.
PMID- 28401241
TI - Synthesis and photocatalytic H2 evolution properties of four titanium-oxo
clusters based on a cyclohex-3-ene-1-carboxylate ligand.
AB - Four titanium-oxo-clusters with cyclohex-3-ene-1-carboxylate (Cec) ligands,
Ti6(MU2-O)2(MU3-O)2(Cec)4(OiPr)12 (PTC-91; HOiPr = isopropanol), Ti6(MU3
O)6(Cec)6(OiPr)6 (PTC-92 and PTC-93) and H2[Ti18(MU2-O)11(MU3-O)14(Cec)20(OiPr)4]
(PTC-94), have been solvothermally synthesized under different conditions,
respectively. These clusters with the same Cec ligand show totally different
structures, and they are stable in water and other common solvents. The Ti6
clusters with different conformations are presented in PTC-91, PTC-92 and PTC-93,
while PTC-94 is an unusual Ti18 cluster. The photocatalytic studies reveal that
PTC-91 and PTC-94 have good H2 evolution ability.
PMID- 28401242
TI - Aluminum complexes derived from a hexadentate salen-type Schiff base: synthesis,
structure, and catalysis for cyclic carbonate synthesis.
AB - Different aluminum complexes were synthesized by the reaction of aluminum alkyls
with a hexadentate salen-type Schiff base. The reaction of N,N'-bis(3,5-di-tert
butylsalicylidene)-2,2'-(ethylenedioxy)dianiline (LH2) with one equiv. of AlMe3
in toluene at 100 degrees C proceeded by methane elimination to produce the
intermediate methyl complex [AlMeL] (1), and then subsequent intramolecular
methyl migration to give the aluminum complex [AlL'] (2) [L' = (2-O-3,5
tBu2C6H2)CH[double bond, length as m-dash]NC6H4OCH2CH2OC6H4NCH(Me)(2'-O-3',5'
tBu2C6H2)]. The reaction of the same ligand with AlEt3 under the same
experimental conditions involved ethane elimination, ethylene elimination and
intramolecular hydrogen migration, and led to the complex [AlL''] (3) [L'' = (2-O
3,5-tBu2C6H2)CH[double bond, length as m-dash]NC6H4OCH2CH2OC6H4NCH2(2'-O-3',5'
tBu2C6H2)]. However, the interaction of two equivalents of AlMe3 and AlEt3
afforded the corresponding binuclear complexes [(AlMe2)2L] (4) and [(AlEt2)2L]
(5), respectively, and no methyl or hydrogen migration was found. The solid-state
structures of aluminum complexes 1-3 were determined by single-crystal X-ray
diffraction. It was found that complexes 2-5 show a very effective catalytic
activity for the cycloaddition of epoxides and CO2 in the presence of NBu4Br as a
cocatalyst at atmospheric pressure.
PMID- 28401243
TI - Two-shell structured PMAA@CeO2 nanocontainers loaded with 2-mercaptobenzothiazole
for corrosion protection of damaged epoxy coated AA 2024-T3.
AB - In this work, novel two-shell structured inhibitor-loaded poly(methacrylic
acid)@cerium oxide (PMAA@CeO2) nanocontainers were synthesised and characterized.
The purpose of the nanocontainers is to increase the corrosion protection
provided by an epoxy coating applied to an aerospace alloy (AA 2024-T3). The
(PMAA@CeO2) nanocontainers with diameters of 550 nm were synthesised by a four
step process with the method of distillation precipitation polymerization for the
synthesis of the inner PMAA layer, and the sol-gel method for the development of
the outer CeO2 layer. The loaded nanocontainers were characterized by scanning
and transmission electron microscopies. The corrosion protection properties of
the epoxy coated AA 2024-T3 with 2-mercaptobenzothiazole (2-MBT) loaded PMAA@CeO2
nanocontainers were evaluated with and without artificial scribes by
electrochemical impedance spectroscopy (EIS). The results indicated that the
epoxy coating containing the 2-MBT-loaded nanocontainers provided enhanced
protection of the AA 2024-T3 substrate.
PMID- 28401244
TI - Integrated 68Ga-HBED-CC-PSMA-PET/MRI in patients with suspected recurrent
prostate cancer.
AB - AIM: Evaluate the diagnostic accuracy of 68Ga-labeled HBED-CC-PSMA-PET/MRI for
detection of recurrent PCa in comparison to PET/CT. METHODS: 48 patients with
suspected recurrent PCa underwent PET/CT after injection of the 68Ga-HBED-CC-PSMA
ligand followed by integrated PET/MRI. Image analysis was performed by nuclear
medicine physicians and radiologists with respect to the detection of lymph node
metastases, bone metastases and local recurrence of the tumour. Image quality was
evaluated visually based on a three-point ordinal scale. RESULTS: From 48
patients initially examined, 25 were finally eligible for qualitative and
quantitative image evaluation. In 14 patients, neither PET/CT nor PET/MRI found
tumour lesions, and 9 patients were excluded from image analysis due to a
pronounced extinction artifact around the urinary bladder (halo). In comparison
to 68Ga-HBED-CC-PSMA-PET/CT, 68Ga-HBED-CC-PSMA-PET/MRI identified 14 vs. 9 local
recurrences in the prostate bed and 23 vs. 20 PET-positive lymph nodes, and 4 vs.
4 PET-positive bone lesions, respectively. While the improved detection of
suspicious lymph nodes was primarily attributable to the PET component, the
advantageous detection of tumour recurrences in the prostate bed was chiefly
referable to the superior soft-tissue contrast of the MR component of integrated
PET/MRI. Analysis of SUVmax revealed that 68Ga-HBED-CC-PSMA-PET/MRI provided
significantly higher SUVmax compared to 68Ga-HBED-CC-PSMA-PET/CT (17.6, range 2.0
49.6, and 15.1, range 3.5-36.8, respectively, p = 0.0019). CONCLUSION: 68Ga-HBED
CC-PSMA-PET/MRI was found to be superior as compared to 68Ga-HBED-CC-PSMA-PET/CT
in the detection of PSMA-expressing prostate bed recurrences.
PMID- 28401245
TI - Automating Clinical Score Calculation within the Electronic Health Record. A
Feasibility Assessment.
AB - OBJECTIVES: Evidence-based clinical scores are used frequently in clinical
practice, but data collection and data entry can be time consuming and hinder
their use. We investigated the programmability of 168 common clinical calculators
for automation within electronic health records. METHODS: We manually reviewed
and categorized variables from 168 clinical calculators as being extractable from
structured data, unstructured data, or both. Advanced data retrieval methods from
unstructured data sources were tabulated for diagnoses, non-laboratory test
results, clinical history, and examination findings. RESULTS: We identified 534
unique variables, of which 203/534 (37.8%) were extractable from structured data
and 269/534 (50.4.7%) were potentially extractable using advanced techniques.
Nearly half (265/534, 49.6%) of all variables were not retrievable. Only 26/168
(15.5%) of scores were completely programmable using only structured data and
43/168 (25.6%) could potentially be programmable using widely available advanced
information retrieval techniques. Scores relying on clinical examination findings
or clinical judgments were most often not completely programmable. CONCLUSION:
Complete automation is not possible for most clinical scores because of the high
prevalence of clinical examination findings or clinical judgments - partial
automation is the most that can be achieved. The effect of fully or partially
automated score calculation on clinical efficiency and clinical guideline
adherence requires further study.
PMID- 28401247
TI - [Erratum to: Mucosal alterations - what is the cause?]
PMID- 28401246
TI - Technology-Mediated Interventions and Quality of Life for Persons Living with
HIV/AIDS. A Systematic Review.
AB - BACKGROUND: As HIV/AIDS is considered a chronic disease; quality of life (QoL)
has become an important focus for researchers and healthcare providers.
Technology-mediated interventions have demonstrated improved clinical
effectiveness in outcomes, such as viral suppression, for persons living with
HIV/AIDS (PLWH). However, the evidence to support the impact of these
interventions on QoL is lacking. OBJECTIVES: The aim of this paper was to assess
the impact of technology-mediated interventions on QoL and to identify the
instruments used to measure the QoL of PLWH. METHODS: For this review we followed
the PRISMA guidelines. A literature search was conducted in PubMed, CINAHL,
Cochrane, and EMBASE databases in April 2016. Inclusion criteria limited articles
to those with technology-mediated interventions as compared to usual care;
articles with the population defined as HIV-infected patients; and articles with
QoL measured as a health outcome in randomized controlled trials. The Cochrane
Collaboration Risk of Bias Tool was used to assess study quality. RESULTS: Of the
1,554 peer-reviewed articles returned in the searches, 10 met the inclusion
criteria. This systematic review identified four types of technology-mediated
interventions and two types of QoL instruments used to examine the impact of
technology-mediated interventions on PLWH. Four studies of technology-mediated
interventions resulted in improvement in QoL. Four studies considered QoL as a
secondary outcome and resulted in a negative or neutral impact on QoL. Overall,
four studies had a low risk of bias, one study had a moderate risk of bias, and
the other five studies had a high risk of bias. CONCLUSIONS: The evidence to
support the improvement of QoL using technology-mediated interventions is
insufficient. This lack of research highlights the need for increased study of
QoL as an outcome measure and the need for consistent measures to better
understand the role of technology-mediated interventions in improving QoL for
PLWH.
PMID- 28401248
TI - [Nasal turbinate surgery].
AB - The nose forms the first 8 cm of the upper respiratory tract and is responsible
for cleansing, humidification, and temperature control of the supplied air. This
is also referred to as conditioning. The nasal valve region, formed by the head
of the lower nasal concha, portions of the cartilaginous septum, and the upper
lateral cartilage, is responsible for diffusing and accelerating the respiratory
airflow. Prerequisite are regular mucociliary clearance and sufficient air
passage. Hypertrophy of the lower nasal turbinate is one of the most common
causes of symptomatic nasal congestion. In unclear cases, rhinometric procedures
are available. In addition to conservative therapy of allergic or vasomotor
rhinitis by specific immunotherapy or topical corticoids, numerous interventional
procedures are available to reduce conchal tissue. All modern methods have a high
degree of protection of the respiratory mucosa in common.
PMID- 28401249
TI - Socioeconomic gradients of cardiovascular risk factors in China and India:
results from the China health and retirement longitudinal study and longitudinal
aging study in India.
AB - OBJECTIVES: Cardiovascular disease has become a major public health challenge in
developing countries. The goal of this study is to compare socioeconomic status
(SES) gradients of cardiovascular risk factors (CVRF) both within and between
China and India. METHODS: We used multivariable logistic regression models to
examine the associations between SES and CVRF, using data from the China health
and retirement longitudinal study and the longitudinal aging study in India.
RESULTS: The results showed that, compared to illiteracy, the odds ratios of
completing junior high school for high-risk waist circumference were 4.99 (95%
confidence interval: 1.77-14.06) among Indian men, 3.42 (95% confidence interval:
1.66-7.05) among Indian women, but 0.74 (95% confidence interval: 0.59-0.92)
among Chinese women. Similar patterns were observed between educational
attainment and high-risk body mass index, and between education and hypertension,
based on self-reported physician diagnosis and direct blood pressure
measurements. CONCLUSIONS: SES is associated with CVRF in both China and India.
However, this relationship showed opposite patterns across two countries,
suggesting that this association is not fixed, but is subjective to underlying
causal pathways, such as patterns of risky health behaviors and different social
and health policies.
PMID- 28401250
TI - [Skeletal hemangiomas].
AB - Hemangiomas are benign tumors, which are mainly composed of neoplastic blood
vessels. The exact pathogenesis is still unclear. They are the most common benign
spinal tumors and also occur less commonly in the bones of the extremities.
Hemangiomas are often clinically asymptomatic and are diagnosed as incidental
findings. Women are affected more frequently than men (2:1). The X-ray and
computed tomography (CT) diagnostics typically demonstrate the classical
honeycombing or vertically orientated lucencies separated by thickened cancellous
bone in the affected skeletal section. Vertebral hemangiomas are hyperintense in
both T1 and T2-weighted magnetic resonance imaging (MRI). The treatment of
vertebral hemangiomas ranges from irradiation, embolization and vertebroplasty to
operative decompression, resection of the tumor and instrumented stabilization.
In the long bones intralesional curettage and bone grafting with additive
osteosynthesis is the main treatment modality. The prognosis for osseous
hemangiomas is good.
PMID- 28401251
TI - Delayed Myocardial Enhancement in Pediatric Hypertrophic Cardiomyopathy:
Correlation with LV Function, Echocardiography, and Demographic Parameters.
AB - Our aim was (1) to detect the presence of fibrosis by Cardiac magnetic resonance
imaging (CMR) in the pediatric age group. (2) Correlate CMR findings with
demographic data, LV function, and other echocardiographic parameters. We studied
40 pediatric patients diagnosed as HCM by echocardiography. All patients were
subjected to clinical examination (in which the NYHA classification was
determined for each patient), echocardiography, and CMR. CMR was done on a 1.5T
Philips Achieva scanner in SSFP with delayed myocardial enhancement (DE-MRI). All
demographic and functional parameters as well as pressure gradient across left
ventricular outflow tract (LVOT) were correlated with the percentage of
myocardial enhancement. We studied 13 female and 27 male patients from 45 days up
to 18 years. The mean percentage of DE-MRI was 9.7 +/- 9%. We found significant
correlation between the NYHA classification and the pressure gradient across the
LVOT (P = < 0.001) as well as the percentage of DE-MRI (P = 0.004). The
percentage of DE-MRI showed positive correlation with LV myocardial mass index (P
= 0.042). It didn't correlate with any other demographic or LV functional cardiac
parameters. A good positive correlation was detected between the percentage of DE
MRI and the severity of pressure gradient across LVOT measured by
echocardiography (r = 0.69 and P = <0.001). We found a significant correlation
between the percentage of DE-MRI in children with HCM and the pressure gradient
across LVOT, NYHA classification, and LV myocardial mass. This may help in the
further management of those patients, planning for follow-up, and prognosis of
the disease.
PMID- 28401252
TI - Evaluation of Ventricular Septal Defect with Special Reference to the Spontaneous
Closure Rate, Subaortic Ridge, and Aortic Valve Prolapse II.
AB - The medical records of 2283 patients with ventricular septal defect (VSD) were
reviewed to determine spontaneous closure, left ventricular-to-right atrial
shunt, subaortic ridge, and aortic valve prolapse. One thousand eight hundred and
twenty-three patients had been followed 1 month to 26 years (median 4 years) by
echocardiography. Most of 460 patients could not be followed due to
transportation of the institution. VSD was perimembranous in 68.8% (1255),
trabecular muscular in 21.7% (395), muscular outlet in 6% (109), muscular inlet
in 2.6% (48), and doubly committed subarterial in 0.9% (16). Defect size was
classified in 66.8% (1218) as small, in 15.7% (286) as moderate, and in 17.5%
(319) as large. VSD closed spontaneously in 18.8% (343 of 1823 patients) by ages
40 days to 24.9 years (median, 1.8 years). One hundred fifty-seven of 1255
perimembranous defects (12.5%) and 167 of 395 trabecular muscular defects (42%)
closed spontaneously (p < 0.001). Defect size became small in 306 (16.8%) of
patients with VSD at a median of 2.5 years. Aneurysmal transformation was
detected in 32.9% (600), left ventricular-to-right atrial shunt in 9.7% (176),
subaortic ridge in 2.6% (48) of 1823 patients who were followed. In 381 (20.9%)
of the 1823 patients, the VSD had been closed by a surgical or transcatheter
technique. Surgery is required in one-fifth of patients with subaortic ridge or
aortic valve prolapse. In conclusion, isolated VSDs are usually benign
abnormalities that tend to shrink and close spontaneously.
PMID- 28401253
TI - Uncomplicated Acute Diverticulitis: Identifying Risk Factors for Severe Outcomes.
AB - BACKGROUND: The management of uncomplicated (Modified Hinchey Classification Ia)
acute diverticulitis (AD) has become increasingly conservative, with a focus on
symptomatic relief and supportive management. Clear criteria for patient
selection are required to implement this safely. This retrospective study aimed
to identify risk factors for severe clinical course in patients with
uncomplicated AD. MATERIALS AND METHODS: Patients admitted to General Surgery at
two New Zealand tertiary centres over a period of 18 months were included.
Univariate and multivariate analyses were carried out in order to identify
factors associated with a more severe clinical course. This was defined by three
endpoints: need for procedural intervention, admission >7 days and 30-day
readmission; these were analysed separately and as a combined outcome. RESULTS:
Uncomplicated AD was identified in 319 patients. Fifteen patients (5%) required
procedural intervention; this was associated with SIRS (OR 3.92). Twenty-two
(6.9%) patients were admitted for >7 days; this was associated with patient
reported pain score >8/10 (OR 5.67). Thirty-one patients (9.8%) required
readmission within 30 days; this was associated with pain score >8/10 (OR 6.08)
and first episode of AD (OR 2.47). Overall, 49 patients had a severe clinical
course, and associated factors were regular steroid/immunomodulator use (OR
4.34), pain score >8/10 (OR 5.9) and higher temperature (OR 1.51) and CRP >=200
(OR 4.1). CONCLUSION: SIRS, high pain score and CRP, first episode and regular
steroid/immunomodulator use were identified as predictors of worse outcome in
uncomplicated AD. These findings have the potential to inform prospective
treatment decisions in this patient group.
PMID- 28401254
TI - Genomic models with genotype * environment interaction for predicting hybrid
performance: an application in maize hybrids.
AB - KEY MESSAGE: A new genomic model that incorporates genotype * environment
interaction gave increased prediction accuracy of untested hybrid response for
traits such as percent starch content, percent dry matter content and silage
yield of maize hybrids. The prediction of hybrid performance (HP) is very
important in agricultural breeding programs. In plant breeding, multi-environment
trials play an important role in the selection of important traits, such as
stability across environments, grain yield and pest resistance. Environmental
conditions modulate gene expression causing genotype * environment interaction (G
* E), such that the estimated genetic correlations of the performance of
individual lines across environments summarize the joint action of genes and
environmental conditions. This article proposes a genomic statistical model that
incorporates G * E for general and specific combining ability for predicting the
performance of hybrids in environments. The proposed model can also be applied to
any other hybrid species with distinct parental pools. In this study, we
evaluated the predictive ability of two HP prediction models using a cross
validation approach applied in extensive maize hybrid data, comprising 2724
hybrids derived from 507 dent lines and 24 flint lines, which were evaluated for
three traits in 58 environments over 12 years; analyses were performed for each
year. On average, genomic models that include the interaction of general and
specific combining ability with environments have greater predictive ability than
genomic models without interaction with environments (ranging from 12 to 22%,
depending on the trait). We concluded that including G * E in the prediction of
untested maize hybrids increases the accuracy of genomic models.
PMID- 28401255
TI - Contaminants in Liquid Organic Fertilizers Used for Agriculture in Japan.
AB - To provide an overview of anthropogenic contaminants in liquid organic
fertilizers (LOFs), products from four biogas plants in Kyushu, Japan, were
analyzed for a wide range of contaminants, including copper, cadmium, tributyltin
(TBT), dibutyltin (DBT), perfluorooctane sulfonate, 952 semi-volatile organic
compounds, and 89 antibiotics. The highest concentrations of copper (31.1 mg/L)
and cadmium (0.08 mg/L) were found in LOFs from the Hita biogas plant. Only
ofloxacin and sulfapyridine were detected in total 89 antibiotics screened. TBT,
DBT, and perfluorooctane sulfonate were present at low concentrations in the LOFs
from all four locations. Among the 952 semi-volatile organic compounds, 78
compounds were detected in at least one sample and were present at concentrations
between 1.2 and 139.6 mg/L. On the basis of comparisons with previous studies and
quality standards for the use of organic fertilizers, the concentrations of
contaminants in the studied LOFs indicate that they might be safe for
agricultural purposes.
PMID- 28401258
TI - Tumor-associated myeloid cells as guiding forces of cancer cell stemness.
AB - Due to their ability to differentiate into various cell types and to support
tissue regeneration, stem cells simultaneously became the holy grail of
regenerative medicine and the evil obstacle in cancer therapy. Several studies
have investigated niche-related conditions that favor stemness properties and
increasingly emphasized their association with an inflammatory environment. Tumor
associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are
major orchestrators of cancer-related inflammation, able to dynamically express
different polarized inflammatory programs that promote tumor outgrowth, including
tumor angiogenesis, immunosuppression, tissue remodeling and metastasis
formation. In addition, these myeloid populations support cancer cell stemness,
favoring tumor maintenance and progression, as well as resistance to anticancer
treatments. Here, we discuss inflammatory circuits and molecules expressed by
TAMs and MDSCs as guiding forces of cancer cell stemness.
PMID- 28401256
TI - Immune-mediated cytokine storm and its role in severe dengue.
AB - Dengue remains one of the most important mosquito-borne diseases worldwide.
Infection with one of the serologically related dengue viruses (DENVs) can lead
to a wide range of clinical manifestations and severity. Severe dengue is
characterized by plasma leakage and abnormal bleeding that can lead to shock and
death. There is currently no specific treatment for severe dengue due to gaps in
understanding of the underlying mechanisms. The transient period of vascular
leakage is usually followed by a rapid recovery and is suggestive of the effects
of short-lived biological mediators. Both the innate and the adaptive immune
systems are activated in severe dengue and contribute to the cytokine production.
We discuss the immunological events elicited during a DENV infection and identify
candidate cytokines that may play a key role in the severe manifestations of
dengue and possible interventions.
PMID- 28401257
TI - IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific
T cells for adoptive cell therapy in metastatic melanoma.
AB - Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells
proved to be successful for the treatment of metastatic melanoma patients. Mixed
lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T
cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is
far from optimal. We hypothesized that this is due to tumor intrinsic and
extrinsic factors and aimed to identify and manipulate these factors so to
optimize our clinical, GMP-compliant MLTC protocol. We found that the tumor cell
produced IDO and/or galectin-3, and the accumulation of CD4+CD25hiFoxP3+ T cells
suppressed the expansion of tumor-specific T cells in the MLTC. Strategies to
eliminate CD4+CD25hiFoxP3+ T cells during culture required the depletion of the
whole CD4+ T cell population and were found to be undesirable. Blocking of IDO
and galectin-3 was feasible and resulted in improved efficiency of the MLTC.
Implementation of these findings in clinical protocols for ex vivo expansion of
tumor-reactive T cells holds promise for an increased therapeutic potential of
adoptive cell transfer treatments with tumor-specific T cells.
PMID- 28401259
TI - Mechanism of salinomycin overproduction in Streptomyces albus as revealed by
comparative functional genomics.
AB - The anticoccidial salinomycin is a polyketide produced by Streptomyces albus, and
the high-yield strain BK 3-25 produces 18.0 g/L salinomycin under lab condition.
In order to elucidate the overproduction mechanism, the genome of BK 3-25 was
fully sequenced and compared with the wild-type DSM 41398. Strain BK 3-25 has a
75-kb large deletion, containing type-I polyketide gene cluster PKS-9, and 60
additional InDels and SNVs affecting 55 CDSs, including a 1-bp deletion in type-I
PKS gene cluster PKS-6. Subsequently, individual or combined deletions of the 75
kb region and PKS-6 in the wild-type resulted in improved salinomycin yields from
2.60 to 5.20, 6.90, and 9.50 g/L (53% of BK 3-25), respectively, suggesting a
redirected flux of polyketide precursors to salinomycin biosynthesis. Moreover,
due to the much higher transcription of salinomycin biosynthetic genes (sln) in
the high-yield BK 3-25 than in the wild-type, 13 putative regulatory genes among
the 55 CDSs were individually inactivated and 7 were proved to be negatively
involved in the transcription of sln genes. Combined deletions of two major
negative regulatory genes SLNWT_3357 and SLNWT_7015 caused further improved
transcription of sln genes as well as the yield, from 2.60 to 7.30 g/L (40% of BK
3-25). Therefore, the comparative genomics approach combined with functional
experiments identified that the multiple deletions and mutations of competing
gene clusters and negative regulatory genes are crucial for salinomycin
overproduction, setting an example for rational titer improvement of other
polyketide natural products.
PMID- 28401260
TI - Stent-assisted coiling of wide-neck bifurcation aneurysms with a branch
incorporated in the aneurysm base: long-term follow-up in 49 patients with 53
aneurysms.
AB - PURPOSE: Wide-neck bifurcation intracranial aneurysms (WNBA) with a branch
incorporated in the aneurysm base remain difficult to treat by embolization. We
aim to report our long-term follow-up of stent-assisted coiling (SAC) in this
subgroup of patients. METHODS: This study was approved by our local ethical
committee. A retrospective review of our prospectively maintained database
identified all patients treated in our institution by SAC for a WNBA with a
branch incorporated in the aneurysm base. Technical issues, immediate, long-term
outcomes were evaluated. RESULTS: Between 2007 and 2015, 49 patients with 53
intracranial aneurysms (IAs) (52 unruptured, 1 ruptured) were identified and
successfully treated. No morbidity/mortality occurred. The incorporated branch
was preserved in all patients but one who was treated during a vasospasm phase.
At the first 6-month imaging control, the branch was patent. Immediate occlusion
was near-complete in 11/53 aneurysms (20.8%), neck remnant in 20/53 aneurysms
(37.7%), and incomplete in 22/53 aneurysms (41.5%). Available imaging follow-up
of 47 IAs, ranging from 3 to 84 months (mean 26 months +/- 19.6 months), showed
27 progressive thrombosis (57.4%), 17 stable occlusions (36.2%), 1 minor
recanalization (2.1%), and 2 significant recanalizations that were retreated
(4.3%). The latest imaging control showed 30 near-complete occlusions (63.8%), 13
neck remnants (27.7%), and 4 incomplete occlusions (8.5%). CONCLUSION: Stent
assisted coiling is safe and effective for the treatment of WNBA with a branch
incorporated in the aneurysm base. Despite poor immediate anatomical results,
long-term follow-up shows a high rate of progressive thrombosis achieving
adequate and stable occlusion in most patients.
PMID- 28401261
TI - Angiotensin II induces the aggregation of native and oxidized low-density
lipoprotein.
AB - Modifications of low-density lipoprotein (LDL), such as oxidation and
aggregation, and angiotensin (Ang) peptides are involved in the pathogenesis of
atherosclerosis. Here, we investigated the relationship between one of the Ang
peptides, AngII, and two LDL modifications, oxidation and aggregation. Using
polyacrylamide gel electrophoresis and aggregation assays, we noted that AngII
markedly induced the aggregation of LDL and oxidized LDL (Ox-LDL), and bound to
both the aggregated and non-aggregated forms. In contrast, a peptide (AngIII)
formed by deletion of N-terminal Asp of AngII induced the aggregation of Ox-LDL
but not LDL. From tyrosine fluorescence measurements, we noted that AngII
interacted with two major lipid components in LDL and Ox-LDL, phosphatidylcholine
(PC) and oxidized PC, while AngIII interacted with oxidized PC, but not with PC
and lysophosphatidylcholine. Moreover, results from thiobarbituric acid-reactive
substances assay proved that AngII did not induce oxidation of LDL. These results
suggest that AngII can be involved in the pathogenesis of atherosclerosis by
binding to LDL and Ox-LDL-especially to the major lipid components, PC and
oxidized PC-followed by inducing the aggregation of LDL and Ox-LDL and that the N
terminal Asp of AngII is important for the binding and aggregation specificity of
LDL and Ox-LDL.
PMID- 28401262
TI - Patterns of Arbuscular Mycorrhizal Fungal Distribution on Mainland and Island
Sandy Coastal Plain Ecosystems in Brazil.
AB - Although sandy coastal plains are important buffer zones to protect the coast
line and maintain biological diversity and ecosystem services, these ecosystems
have been endangered by anthropogenic activities. Thus, information on coastal
biodiversity and forces shaping coastal biological diversity are extremely
important for effective conservation strategies. In this study, we aimed to
compare arbuscular mycorrhizal (AM) fungal communities from soil samples
collected on the mainland and nearby islands located in Brazilian sandy coastal
plain ecosystems (Restingas) to get information about AM fungal biogeography and
identify factors shaping these communities. Soil samples were collected in 2013
and 2014 on the beachfront of the tropical sandy coastal plain at six sites
(three island and three mainland locations) across the northeast, southeast, and
south regions of Brazil. Overall, we recorded 53 AM fungal species from field and
trap culture samples. The richness and diversity of AM fungal species did not
differ between mainland and island locations, but AM fungal community assemblages
were different between mainland and island environments and among most sites
sampled. Glomeromycota communities registered from island samples showed higher
heterogeneity than communities from mainland samples. Sandy coastal plains harbor
diverse AM fungal communities structured by climatic, edaphic, and spatial
factors, while the distance from the colonizing source (mainland environments)
does not strongly affect the AM fungal communities in Brazilian coastal
environments.
PMID- 28401263
TI - Mutational and biochemical findings in adults with persistent hypophosphatasemia.
AB - : A majority of adults with persistently low serum alkaline phosphatase values
carry a pathogenic or likely pathogenic variant in the ALPL gene and also have
elevated alkaline phosphatase substrate values in serum and urine. These adults
may fall within the spectrum of the adult form of hypophosphatasia. INTRODUCTION:
The primary objective of this study was to determine what proportion of adults
with persistently low serum alkaline phosphatase values (hypophosphatasemia)
harbor mutations in the ALPL gene or have elevated alkaline phosphatase (ALP)
substrates. Some adults with persistent hypophosphatasemia share clinical and
radiographic features with the adult form of hypophosphatasia (HPP). In HPP, ALPL
mutations result in persistent hypophosphatasemia and ALP substrate accumulation
in plasma (pyridoxal-5-phosphate (PLP)) and urine (phosphoethanolamine (PEA)).
METHODS: Biochemical analyses, including serum ALP activity, bone-specific ALP,
plasma PLP, and urine PEA, were performed in adults with persistent
hypophosphatasemia. Mutational analyses were performed using PCR and Sanger
sequencing methods. Gene variants were classified as pathogenic (P), likely
pathogenic (LP), variants of uncertain significance (VUS), likely benign (LB),
and benign (B). P and LP variants were further grouped as "Positive ALPL
variants" and LB and B grouped as "Negative ALPL variants." RESULTS: Fifty
subjects completed all mutational and biochemical analyses. Sixteen percent
carried only Negative ALPL variants. Of the remaining 42 subjects, 67% were
heterozygous for a P variant, 19% for an LP variant, and 14% for a VUS.
Biochemical results were highly inter-correlated and consistent with the expected
inverse relationship between ALP and its substrates. Subjects harboring Positive
ALPL variants showed lower ALP and BSAP and higher PLP and PEA values compared
with subjects harboring only Negative ALPL variants. Approximately half of all
subjects harboring Positive ALPL variants or ALPL VUS showed elevations in plasma
PLP, and three quarters showed elevations in urine PEA. CONCLUSION: Adults with
persistent hypophosphatasemia frequently harbor ALPL mutations and have elevated
ALP substrates. These adults may fall within the spectrum of the adult form of
hypophosphatasia. Clinicians should take note of persistent hypophosphatasemia in
their patients and be cautious in prescribing bisphosphonates when present.
PMID- 28401265
TI - Dynamic contrast-enhanced MR imaging in osteoid osteoma: relationships with
clinical and CT characteristics.
AB - OBJECTIVE: To correlate dynamic contrast-enhanced magnetic resonance imaging (DCE
MRI) features to clinical and computed tomography (CT) morphological features of
osteoid osteoma (OO). MATERIALS AND METHODS: Our institutional review board
approved this retrospective study, waiving the need for informed consent. We
included the 102 patients treated with interstitial laser ablation for
histologically documented OO at our institution in 2008-2013. DCE-MRI variables
were the time-enhancement pattern and rising slope (Sloperise) and CT variables
were the bone and segment involved (OObone and OOsegment, respectively), OO
location relative to the native cortex (OOcortex), nidus surface area, vessel
sign, and largest neighboring-vessel diameter (Dmaxvessel). Descriptive
statistics and correlations linking DCE-MRI findings to clinical and CT
characteristics were computed. RESULTS: DCE-MRI showed early arterial peak
enhancement in 95 (93%) cases, with a mean Sloperise of 9.30 +/- 8.10. CT
visualized a vessel sign in 84 (82%) cases with a mean Dmaxvessel of 1.10 +/-
0.60 mm. By univariate analysis, Sloperise correlated significantly with pain
duration and Dmaxvessel (r = 0.30, P = 0.003; and r = 0.22, P = 0.03;
respectively). Analysis of variance showed that Sloperise correlated
significantly with OObone (P < 0.001), with a steeper slope for OOs located in
short or flat bones. CONCLUSION: This study suggests more abundant
vascularization of OOs with long-lasting pain and location on short or flat
bones.
PMID- 28401266
TI - Dynamic flux balance analysis with nonlinear objective function.
AB - Dynamic flux balance analysis (DFBA) extends flux balance analysis and enables
the combined simulation of both intracellular and extracellular environments of
microbial cultivation processes. A DFBA model contains two coupled parts, a
dynamic part at the upper level (extracellular environment) and an optimization
part at the lower level (intracellular environment). Both parts are coupled
through substrate uptake and product secretion rates. This work proposes a Karush
Kuhn-Tucker condition based solution approach for DFBA models, which have a
nonlinear objective function in the lower-level part. To solve this class of DFBA
models an extreme-ray-based reformulation is proposed to ensure certain
regularity of the lower-level optimization problem. The method is introduced by
utilizing two simple example networks and then applied to a realistic model of
central carbon metabolism of wild-type Corynebacterium glutamicum.
PMID- 28401267
TI - Paeonol protects against TNF-alpha-induced proliferation and cytokine release of
rheumatoid arthritis fibroblast-like synoviocytes by upregulating FOXO3 through
inhibition of miR-155 expression.
AB - BACKGROUND: Fibroblast-like synoviocytes (FLS) play an essential role in the
pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis.
Paeonol (Pae) is a phenolic compound found in many traditional Chinese medicine
remedies. However, the effects of Pae on TNF-alpha-stimulated FLS and the
underlying molecular mechanism are unknown. In this study, we aimed to
investigate the anti-proliferative and anti-inflammatory effect of Pae against
activated FLS. MATERIALS AND METHODS: Rheumatoid arthritis FLS (RA-FLS) were pre
treated with different doses (25, 50, and 100 uM) of Pae or miR-155 inhibitor for
30 min or transfected with miR-155 mimic, and then treated with 50 ng/mL of tumor
necrosis factor alpha (TNF-alpha) for 1 h. Cells that were untreated served as
control. At 24 h after drug pretreatment, the proliferation of FLS was detected
using the MTT assay. The concentrations of interleukin IL-6 and IL-1beta in cell
culture supernatant were examined by enzyme-linked immunosorbent assay (ELISA),
and mRNA levels of Foxo3 and miR-155 expression in FLS were quantified by reverse
transcription-polymerase chain reaction (RT-PCR). Protein expressions of forkhead
box O3 (FOXO3), cyclin D1, and c-Myc were detected by Western Blot. RESULTS: TNF
alpha induced the proliferation of FLS, whereas Pae inhibited this proliferation
in a dose-dependent manner. Pae attenuated TNF-alpha-induced production of IL-6
and IL-1beta, and inhibited the expression of miR-155 in a dose-dependent manner.
In addition, miR-155 inhibitor decreased TNF-alpha-induced proliferation of FLS,
and attenuated TNF-alpha-induced production of IL-6 and IL-1beta. In addition,
pretreatment with different doses of Pae or miR-155 inhibitor markedly attenuated
TNF-alpha-induced decrease in protein expression of FOXO3 in FLS. Mechanistic
studies revealed FOXO3 as miR-155-5p direct target and inhibition of FOXO3 led to
the abolishment of Pae protective effects. CONCLUSIONS: Paeonol protected against
TNF-alpha-induced proliferation and cytokine release of FLS by decreasing the
expression of miR-155 and upregulating its target FOXO3.
PMID- 28401268
TI - Erratum to: Hymenobacter knuensis sp. nov., Isolated From River Water.
PMID- 28401270
TI - [Dithranol].
PMID- 28401269
TI - Vinculin in cell-cell and cell-matrix adhesions.
AB - Vinculin was identified as a component of focal adhesions and adherens junctions
nearly 40 years ago. Since that time, remarkable progress has been made in
understanding its activation, regulation and function. Here we discuss the
current understanding of the roles of vinculin in cell-cell and cell-matrix
adhesions. Emphasis is placed on the how vinculin is recruited, activated and
regulated. We also highlight the recent understanding of how vinculin responds to
and transmits force at integrin- and cadherin-containing adhesion complexes to
the cytoskeleton. Furthermore, we discuss roles of vinculin in binding to and
rearranging the actin cytoskeleton.
PMID- 28401271
TI - [Light protection for xeroderma pigmentosum].
AB - Xeroderma pigmentosum is a rare autosomal recessive disorder which is caused by
germinal mutations responsible for the repair of ultraviolet (UV) radiation
induced DNA lesions. It is characterized by hypersensitivity to UV radiation,
poikiloderma, ocular surface disease, and in some patients pronounced sunburn and
neurological disease. Patients have a very high risk of developing ocular and
skin cancer on exposed body sites. No cure is available for these patients except
complete protection from all types of UV radiation.
PMID- 28401272
TI - [Sun protection factor 50+ : Pro and contra].
AB - The use of sunscreens with sun protection factors beyond 50 is controversial. In
order to avoid misleading the consumer, several countries have already decided
not to declare SPF beyond 50 on sunscreen products. Arguments against high SPF
include the following: the risk of imbalanced protection, which could increase
the risk of damage caused by longer-wave ultraviolet radiation; imparting a false
sense of safety, which could lead to the extension of sun exposure times; health
risks from higher concentrations of filter substances; and the only marginally
higher blockade provided by high SPF sunscreens. On the other hand, it has been
realized that the functional SPF of sunscreens remains far behind the declared
SPF in the practical application and, therefore, the use of higher SPF in
sensitive individuals and during strong UV exposure could make sense.
PMID- 28401273
TI - Suicide mortality among male veterans discharged from Veterans Health
Administration acute psychiatric units from 2005 to 2010.
AB - PURPOSE: The purpose of this study was to calculate suicide rates and identify
correlates of risk in the year following discharge from acute Veterans Health
Administration psychiatric inpatient units among male veterans discharged from
2005 to 2010 (fiscal years). METHODS: Suicide rates and standardized mortality
ratios were calculated. Descriptive analyses were used to describe suicides and
non-suicides and provide base rates for interpretation, and unadjusted and
adjusted proportional hazard models were used to identify correlates of suicide.
RESULTS: From 2005 to 2010, 929 male veterans died by suicide in the year after
discharge and the suicide rate was 297/100,000 person-years (py). The suicide
rate significantly increased from 234/100,000 py (95% CI = 193-282) in 2005 to
340/100,000 py (95% CI = 292-393) in 2008, after which it plateaued. Living in a
rural setting, HR (95% CI) = 1.20 (1.05, 1.36), and being diagnosed with a mood
disorder such as major depression, HR (95% CI) = 1.60 (1.36, 1.87), or other
anxiety disorder, HR (95% CI) = 1.52 (1.24, 1.87), were associated with increased
risk for suicide. CONCLUSIONS: Among male veterans, the suicide rate in the year
after discharge from acute psychiatric hospitalization increased from 2005 to
2008, after which it plateaued. Prevention efforts should target psychiatrically
hospitalized veterans who live in rural settings and/or are diagnosed with mood
or other anxiety disorders.
PMID- 28401274
TI - Posttraumatic stress disorder, trauma, and reconciliation in South Sudan.
AB - PURPOSE: South Sudan is embroiled in a conflict that erupted in December 2013.
This study examines what people in South Sudan think is necessary to achieve
reconciliation and how trauma exposure and PTSD are associated with those
beliefs. METHODS: 1525 participants (51.0% female) were selected using random and
purposive sampling in six states and Abyei. Participants reported on traumatic
events, PTSD symptoms, and attitudes towards reconciliation mechanisms. RESULTS:
Results indicated that 40.7% met symptom criteria for probable PTSD. Most
participants thought reconciliation was not possible without prosecuting
perpetrators or compensating victims and did not support amnesty. Participants
with probable PTSD were more likely to endorse confessions (OR 2.42 [1.75,
3.35]), apologies (OR 2.04 [1.46, 2.83]), and amnesty (OR 1.58 [1.21, 2.08]), and
to report that compensation (OR 2.32 [1.80, 3.00]) and prosecution (OR 1.47
[1.15, 1.89]) were not necessary for reconciliation. The more traumatic events
people experienced, the more they endorsed criminal punishment for perpetrators
(OR 1.07 [1.04, 1.10]) and the less they endorsed confessions (OR 0.97 [0.95,
0.99]). CONCLUSIONS: People with PTSD may prioritize ending violence via
opportunities for reconciliation, while those with more trauma exposure may
support more punitive mechanisms. Policy makers should take mental health
treatment and trauma into account when designing conflict mitigation, peace
building, and justice mechanisms.
PMID- 28401275
TI - Dimensionality of DSM-5 posttraumatic stress disorder and its association with
suicide attempts: results from the National Epidemiologic Survey on Alcohol and
Related Conditions-III.
AB - BACKGROUND: Emerging confirmatory factor analytic (CFA) studies suggest that
posttraumatic stress disorder (PTSD) as defined by the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5) is best characterized by seven
factors, including re-experiencing, avoidance, negative affect, anhedonia,
externalizing behaviors, and anxious and dysphoric arousal. The seven factors,
however, have been found to be highly correlated, suggesting that one general
factor may exist to explain the overall correlations among symptoms. METHODS:
Using data from the National Epidemiologic Survey on Alcohol and Related
Conditions-III, a large, national survey of 36,309 U.S. adults ages 18 and older,
this study proposed and tested an exploratory bifactor hybrid model for DSM-5
PTSD symptoms. The model posited one general and seven specific latent factors,
whose associations with suicide attempts and mediating psychiatric disorders were
used to validate the PTSD dimensionality. RESULTS: The exploratory bifactor
hybrid model fitted the data extremely well, outperforming the 7-factor CFA
hybrid model and other competing CFA models. The general factor was found to be
the single dominant latent trait that explained most of the common variance
(~76%) and showed significant, positive associations with suicide attempts and
mediating psychiatric disorders, offering support to the concurrent validity of
the PTSD construct. CONCLUSIONS: The identification of the primary latent trait
of PTSD confirms PTSD as an independent psychiatric disorder and helps define
PTSD severity in clinical practice and for etiologic research. The accurate
specification of PTSD factor structure has implications for treatment efforts and
the prevention of suicidal behaviors.
PMID- 28401276
TI - [Chronic pelvic pain syndrome : Treatment options using osteopathy].
AB - Urogenital problems are dramatically increasing; especially chronic pelvic pain
syndrome (CPPS) poses a major challenge for physicians and therapists. Few forms
of therapy have been able to promise relief because the cause of CPPS remains
unclear. Functional complaints are increasingly discussed as triggers.
Osteopathic treatment has been reported to help many patients in recent years. In
this article, the approach and osteopathic point of view of functional complaints
are presented. In addition, possible causes for the development of CPPS and
important anatomical structures that are directly involved in it are explained.
Further interdisciplinary research of functional relationships would be desirable
in the future.
PMID- 28401277
TI - Stress distribution is deviated around the aperture of the femoral tunnel in the
anatomic anterior cruciate ligament reconstruction.
AB - PURPOSE: Final tunnel location in the anterior cruciate ligament (ACL)
reconstruction is unpredictable due to tunnel widening and/or transposition. The
mechanical stress around the tunnel aperture seems to be a major factor but is
not fully investigated. The purpose of this study was to measure the stress from
the ACL graft around the tunnel aperture when the ACL graft tension reaches its
peak. METHODS: Six cadaveric knees were used. Single-bundle ACL reconstruction
was performed using a hamstrings graft. Both femoral and tibial tunnels were
created at the centre of the original ACL footprint. A 7-mm-internal-diameter
aluminium cylinder with pressure sensors was placed in the femoral tunnel.
Hamstrings graft with a microtension sensor was inserted. After fixation, passive
extension-flexion was performed while monitoring the tunnel aperture pressure and
the graft tension simultaneously. The pressure on the femoral tunnel aperture
when the ACL graft tension reach its peak was compared between four directions.
RESULTS: The ACL graft tension peaked (67 +/- 49 N) at full extension (-5.8 +/-
4.1 degrees ). Pressure at the femoral tunnel aperture was different between
different directions (p < 0.01). Distal part had significantly larger pressure
(1.7 +/- 1.3 MPa) than the other directions (p < 0.01). Second largest pressure
was carried in the anterior part (0.6 +/- 0.5 MPa), followed by proximal and
posterior parts (0.4 +/- 0.3, 0.2 +/- 0.2 MPa respectively). CONCLUSION: The
stress distribution at the femoral tunnel aperture is not equal in different
directions, while the distal part dominantly bears the stress from the ACL graft.
Surgeons should pay close attention to the distal edge of the femoral tunnel
which should be inside the anatomic ACL footprint eventually.
PMID- 28401278
TI - Arthroscopic reduction and fixation for displaced greater tuberosity fractures
using the modified suture-bridge technique.
AB - PURPOSE: The aim of this study was to evaluate the early clinical outcomes of
arthroscopic treatment of avulsion or comminuted fractures of the greater
tuberosity (GT) using a modified suture-bridge technique. METHODS: Between
February 2013 and November 2015, 14 patients with displaced or comminuted
fractures of GT were arthroscopically treated using a modified suturebridge
technique. Displacement of the GT fragments was > 3 mm in any plane. An analysis
of follow-up results including the University of California, Los Angeles (UCLA)
shoulder scale; the shoulder index of the American Shoulder and Elbow Surgeons
(ASES); the simple shoulder test (SST); and shoulder range of motion (ROM), is
presented. RESULTS: Mean duration of follow up is 18.9 months (range, 6-30). Mean
age of patients was 62.9 years (range, 49-74). Postoperatively, the outcomes were
rated as excellent, good and fair in two, 11 and one patient, respectively based
on the UCLA score. At the most recent follow-up, the average UCLA score increased
to 32 points, the ASES score increased to 97.5 points, and the SST score
increased to 11 points. Average forward flexion was 153.6 degrees , average
abduction was 158.6 degrees , average external rotation in the neutral position
was 38.6 degrees , and internal rotation increased to the 12th thoracic vertebral
level. CONCLUSION: Early follow-up outcomes of the arthroscopic modified suture
bridge technique used for avulsion or comminuted GT fractures are promising. The
technique can be used as one of the therapeutic modalities for GT fractures.
PMID- 28401280
TI - "Fish-mouth" vertebrae in sickle cell anemia.
PMID- 28401281
TI - CT angiography and 3D imaging in aortoiliac occlusive disease: collateral
pathways in Leriche syndrome.
AB - Collateral pathways in aortoiliac occlusive disease are essential for arterial
blood flow to the abdomen, pelvis, and lower extremities. These pathways can be
broadly divided into systemic-systemic, visceral-visceral, and systemic-visceral
collateral networks. MDCT angiography is the most commonly used modality for the
diagnostic evaluation of patients with aortoiliac occlusive disease, allowing
excellent evaluation of stenotic arterial segments, as well as beautifully
illustrating resulting collateral pathways (particularly when utilizing 3D
reconstruction techniques). This article seeks to familiarize radiologists with
the most common patterns of aortoiliac occlusion and associated arterial
collateral pathways utilizing CT angiography.
PMID- 28401279
TI - Current concepts in the diagnosis and management of extra-articular hip
impingement syndromes.
AB - PURPOSE: Extra-articular hip impingement syndromes encompass a group of
conditions that have previously been an unrecognised source of pain in the hip
and on occasion been associated with intra-articular hip impingement as well. As
arthroscopic techniques for the hip continue to evolve, the importance of these
conditions has been recognised recently and now form an important part of the
differential of an individual presenting with hip pain. The aim of this article,
therefore, is to provide the reader with an evidence-based and comprehensive
update of these syndromes. METHODS: By reviewing past literature, the anatomy,
pathophysiology, clinical features and the management of the five common extra
articular hip impingement syndromes were described. RESULTS: The common extra
articular impingement syndromes are: 1) Ischiofemoral impingement: quadratus
femoris muscle becomes compressed between the lesser trochanter and the ischial
tuberosity. 2) Subspine impingement: mechanical conflict occurs between an
enlarged or malorientated anterior inferior iliac spine and the distal anterior
femoral neck. 3) Iliopsoas impingement: mechanical conflict occurs between the
iliopsoas muscle and the labrum, resulting in distinct anterior labral pathology.
4) Deep gluteal syndrome: pain occurs in the buttock due to the entrapment of the
sciatic nerve in the deep gluteal space. 5) Pectineofoveal impingement: pain
occurs when the medial synovial fold impinges against overlying soft tissue,
primarily the zona orbicularis. Knowledge for these syndromes still remains
limited for reasons mostly relating to their low prevalence and their co
existence with typical femoro-acetabular impingement. CONCLUSIONS: The knowledge
of extra-articular hip impingement syndromes is essential and should form a part
of the differential diagnoses alongside intra-articular pathology including
femoro-acetabular impingement particularly in the younger patient with a non
arthritic hip.
PMID- 28401282
TI - Differentiation of cancerous and inflammatory colorectal perforations using multi
detector computed tomography.
AB - PURPOSE: To determine reliable CT features to distinguish cancerous from
inflammatory colorectal perforations. MATERIALS AND METHODS: A total of 43
patients with surgically and pathologically confirmed colorectal perforation
caused by either colorectal cancer (n =27) or an inflammatory conditions (n = 16)
were identified. Two radiologists independently assessed the contrast-enhanced CT
features for locations of perforation, mural configurations, soft-tissue
alterations, lymphadenopathy, and metastases. Intergroup comparisons for
univariate analysis were performed using Fisher's exact test or chi-square test
for categorical data and Mann-Whitney test for numeric data. Stepwise logistic
regression analysis was conducted with features that were found significant under
the univariate analysis. Interobserver agreement was assessed using intraclass
correlation coefficient (ICC) and kappa test. RESULTS: Maximal mural thickness
>1.39 cm (sensitivity, 100%; specificity, 68.75%), luminal mass or shoulder
formation (sensitivity, 88.89%; specificity, 68.75%), absence of diverticula
(sensitivity, 96.30%; specificity, 50.00%), irregular mural thickening
(sensitivity, 92.59%; specificity, 81.25%), lymphadenopathy (sensitivity, 40.74%;
specificity, 93.75%), and metastases (sensitivity, 25.93%; specificity, 100%)
were significantly frequent in cancerous perforations. The maximal mural
thickness (P = 0.0493, odds ratio = 439.83) and irregular mural thickening (P =
0.0343, odds ratio = 4.69) were identified as the highly distinguished
identifiers. CONCLUSIONS: The CT manifestations of cancerous and inflammatory
colorectal perforations overlap. Definitive diagnosis is not always possible with
imaging alone. The maximal mural thickness >1.39 cm and irregular configuration
of the thickened bowel wall were the two highly statistically significant CT
features that may help order the difference between the two entities.
PMID- 28401283
TI - Magnetic resonance imaging of the scrotum: pictorial review with ultrasound
correlation.
AB - The purpose of this review is to showcase the added value of scrotal magnetic
resonance imaging (MRI) in the workup of neoplastic and non-neoplastic entities.
While ultrasound (US) remains the first-line imaging modality for evaluating
scrotal pathology, MRI may add valuable information, particularly when US
findings are equivocal. The inherent soft tissue resolution characteristics of
MRI, as well as the ability to detect subtle enhancement and provide wider field
of-view imaging, can prove useful in evaluating inconclusive US findings. The
added value of MR in these instances is critical as it may have a significant
impact on patient management.
PMID- 28401284
TI - Targeting the subthalamic nucleus in a preclinical model of alcohol use disorder.
AB - BACKGROUND: The subthalamic nucleus (STN) has only recently been considered to
have a role in reward processing. In rats, inactivation of the STN by lesion or
high-frequency stimulation (HFS) decreases motivation for cocaine but increases
motivation for sucrose. For ethanol, the effect of STN lesion depends on the
individual's baseline intake; decreasing motivation for ethanol in rats with
lower ethanol intake, while increasing motivation for ethanol in rats with higher
but still limited-ethanol intake. However, the involvement of the STN in
behaviour more closely resembling some aspects of alcohol use disorder has not
been assessed. This study aimed to determine the effect of STN lesions on the
escalation of ethanol intake, subsequent increases in the motivation to "work"
for ethanol and the choice of ethanol over a non-drug alternative. RESULTS: We
found that STN lesion prevented increases in ethanol intake observed during
intermittent ethanol access and after a long period of ethanol privation. STN
lesion also decreased the motivation to work for ethanol after escalated intake.
Surprisingly, STN lesion increased the choice of alcohol over saccharin. This was
associated with a blunting of the hedonic responses to the taste of the
reinforcement alternatives. CONCLUSION: These results evidence the involvement of
the STN in different ethanol-motivated behaviours and therefore position the STN
as an interesting target for the treatment of alcohol use disorders.
PMID- 28401286
TI - Identification of odorants in wood of Calocedrus decurrens (Torr.) Florin by
aroma extract dilution analysis and two-dimensional gas chromatography-mass
spectrometry/olfactometry.
AB - General emissions of volatile organic compounds from wood are well investigated,
but only limited information is available on the odor-active substances contained
therein. To close this gap, we aimed at specifically elucidating the odorous
constituents of wood from incense cedar [Calocedrus decurrens (Torr.) Florin];
this material is commonly used for the production of a range of products such as
pencils and interior accessories. Targeted odorant analysis requires specialized
techniques combining modern odorant analytical tools with human-sensory
evaluation. Following this concept, the odor profile of the wood sample was first
evaluated by human-sensory analyses. Then, the most potent wood odorants were
characterized by means of gas chromatography-olfactometry and ranked according to
their odor potency via aroma extract dilution analysis. With use of this
approach, more than 60 odorous substances were detected, and the 22 most potent
odorants were successfully identified by gas chromatography-mass
spectrometry/olfactometry and two-dimensional gas chromatography-mass
spectrometry/olfactometry. Among the main odorants found were a series of
terpenes, several degradation products of fatty acids, and a number of odorants
with a phenolic core moiety. Five odorants are reported here for the first time
as wood odorants, such as gamma-octalactone and 3-phenylpropanoic acid;
thymoquinone was demonstrated for the first time to have a pencil-like odor
quality.
PMID- 28401285
TI - Individual prolactin reactivity modulates response of nucleus accumbens to erotic
stimuli during acute cannabis intoxication: an fMRI pilot study.
AB - RATIONALE: Self-report studies indicate that cannabis could increase sexual
desire in some users. We hypothesized that intoxication increases activation of
brain areas responsive to visual erotica, which could be useful in the treatment
of hypoactive sexual desire disorder, a condition marked by a lack of sexual
desire. OBJECTIVES: The aim of this study is to assess the aphrodisiacal
properties of cannabis. METHODS: We conducted an open-randomized study with 21
heterosexual casual cannabis users. A 3T MRI was used to measure brain activation
in response to erotic pictures. Blood samples were collected to determine the
serum levels of cannabinoids, cortisol and prolactin. Participants were grouped
according to whether they had ever experienced any aphrodisiacal effects during
intoxication (Group A) or not (Group non-A). RESULTS: Intoxication was found to
significantly increase activation in the right nucleus accumbens in the Group A
while significantly decreasing activation in the Group non-A. There was also a
significant interaction between the group and intoxication, with elevated
prolactin in the Group non-A during intoxication. No intoxication-related
differences in subjective picture evaluations were found. CONCLUSION: Cannabis
intoxication increases activation of the right nucleus accumbens to erotic
stimuli. This effect is limited to users whose prolactin is not elevated in
response to intoxication. This effect may be useful in the treatment of low
sexual desire.
PMID- 28401287
TI - Graphene oxide for solid-phase extraction of bioactive phenolic acids.
AB - A solid-phase extraction (SPE) method for the efficient analysis of trace
phenolic acids (PAs, caffeic acid, ferulic acid, protocatechuic acid, cinnamic
acid) in urine was established. In this work, a graphene oxide (GO) coating was
grafted onto pure silica to be investigated as SPE material. The prepared GO
surface had a layered and wrinkled structure that was rough and well organized,
which could provide more open adsorption sites. Owing to its hydrophilicity and
polarity, GO showed higher extraction efficiency toward PAs than reduced GO did,
in agreement with the theoretical calculation results performed by Gaussian 09
software. The adsorption mechanism of PAs on GO@Sil was also investigated through
static state and kinetic state adsorption experiments, which showed a monolayer
surface adsorption. Extraction capacity of the as-prepared material was optimized
using the response surface methodology. Under the optimized conditions, the as
established method provided wide linearity range (2-50 MUg L-1 for protocatechuic
acid and 1-50 MUg L-1 for caffeic acid, ferulic acid, and cinnamic acid) and low
limits of detection (0.25-1 MUg L-1). Finally, the established method was applied
for the analysis of urine from two healthy volunteers. The results indicate that
the prepared material is a practical, cost-effective medium for the extraction
and determination of phenolic acids in complex matrices. Graphical Abstract A
graphene oxide coating was grafted onto pure silica as the SPE material for the
extraction of phenolic acids in urines and the extraction mechanism was also
mainly investigated.
PMID- 28401288
TI - Ionic liquids for the passive sampling of sulfonamides from water-applicability
and selectivity study.
AB - Ionic liquids (ILs) are new-generation, non-volatile solvents which are
designable, and their structure may be specifically adjusted to the current
application needs. Therefore, it is possible to create and apply ILs which
efficiently and selectively extract various analytes from different matrices. It
has already been examined that ILs may be applied as receiving phases in passive
sampling for the long-term water monitoring of PAHs and pharmaceuticals in water.
In this paper, the concept of passive sampling with ILs (PASSIL applied as
receiving phases) was continued and developed using phosphonium-, imidazolium-,
and morpholinium-cation-based ILs. The target group of analytes was
pharmaceuticals which represent one of the most common categories of water
contaminants. Fourteen-day-long extractions using various ILs were performed in
stirred conditions at a constant temperature (20 degrees C). The best extraction
efficiency was achieved for trihexyl(tetradecyl)phosphonium dicyanamide ([P666
14][N(CN)2]). For this preliminary calibration, the sampling rates were
calculated for each sulfonamide. Once again, selectivity was observed in passive
sampling using [P666-14][N(CN)2]. Therefore, PASSIL is seen as a very promising
method for pharmaceutical monitoring in water.
PMID- 28401289
TI - Characterization of odorants in inflatable aquatic toys and swimming learning
devices-which substances are causative for the characteristic odor and
potentially harmful?
AB - Based on the observation of intense and offensive smells in the product group of
aquatic toys, four representative products were exemplarily chosen and
sensorially characterized by an expert panel. Panellists reported mostly almond-
and rubber-like notes for three of the four samples, whereas the smell of the
fourth sample was dominated by organic solvent-associated notes such as "nail
polish-like." To elucidate the molecular reasons of these smells, we isolated the
volatile fraction of the product by solvent extraction and high vacuum
distillation, and identified the main odorants by aroma extract dilution analysis
(AEDA), followed by one- and two-dimensional gas chromatography, with parallel
mass spectrometric and olfactometric detection. Additionally, the materials of
the samples were identified by means of differential scanning calorimetry (DSC),
attenuated total reflectance spectroscopy (ATR-spectroscopy), and Beilstein
halogen test. Between 32 and 46 odors could be detected in each sample by means
of AEDA, whereby five to 13 of these compounds were detectable with by far the
highest dilution factors, and were found to primarily correlate with the smells
of the respective products. Focussing the subsequent identification on these
causative substances led to the successful identification of the majority of
these odorants. Among them were several mono- or di-unsaturated carbonyl
compounds and their epoxidized derivatives, which are typical odorous artefacts
from fatty acid oxidation, but also odor-active organic solvents such as
cyclohexanone, isophorone, and phenol.
PMID- 28401290
TI - Effects of competition on induction of crassulacean acid metabolism in a
facultative CAM plant.
AB - Abiotic drivers of environmental stress have been found to induce CAM expression
(nocturnal carboxylation) in facultative CAM species such as Mesembryanthemum
crystallinum. The role played by biotic factors such as competition with non-CAM
species in affecting CAM expression, however, remains largely understudied. This
research investigated the effects of salt and water conditions on the competition
between M. crystallinum and the C3 grass Bromus mollis with which it is found to
coexist in California's coastal grasslands. We also investigated the extent to
which CAM expression in M. crystallinum was affected by the intensity of the
competition with B. mollis. We found that M. crystallinum had a competitive
advantage over B. mollis in drought and saline conditions, while B. mollis
exerted strong competitive effects on M. crystallinum in access to light and soil
nutrients in high water conditions. This strong competitive effect even
outweighed the favorable effects of salt or water additions in increasing the
biomass and productivity of M. crystallinum in mixture. Regardless of salt
conditions, M. crystallinum did not switch to CAM photosynthesis in response to
this strong competitive effect from B. mollis. Disturbance (i.e., grass cutting)
reduced the competitive pressure by B. mollis and allowed for CAM expression in
M. crystallinum when it was grown mixed with B. mollis. We suggest that moderate
competition with other functional groups can enhance CAM expression in M.
crystallinum, thereby affecting its plasticity and ability to cope with
biological stress.
PMID- 28401291
TI - The human retinoblastoma susceptibility gene (RB1): an evolutionary story in
primates.
AB - The tumor suppressor gene RB1 (Human Retinoblastoma Susceptibility Gene) plays a
prominent role in normal development, gene transcription, DNA replication,
repair, and mitosis. Its complete biallelic dysfunction in retinoblasts is the
main cause of retinoblastoma in the human. Although this gene has been
evolutionary conserved, comparisons between the reference and human RB1 coding
region with its counterparts in 19 non-human primates showed 359 sites where
nucleotide replacements took place during the radiation of these species. These
resulted in missense substitutions in 97 codons, 91 of which by amino acids with
radically different physicochemical properties. Several in frame deletions and
two insertions were also observed in the N-terminal region of the pRB protein
where the highest number of amino acid substitutions and radical amino changes
were found. Fifty-six codons were inferred to be under negative selection and
five under positive selection. Differences in codon usage showed evident
phylogenetic signals, with hominids generally presenting higher indices of codon
bias than other catarrhines. The lineage leading to platyrrhines and, within
platyrrhines, the lineage leading to Saimiri boliviensis showed a high rate of
nucleotide substitutions and amino acids. Finally, several RB1 alterations
associated to retinoblastoma in the human were present in several non-human
primates without an apparent pathological effect.
PMID- 28401292
TI - Choroidal thinning in Fuchs Uveitis Syndrome.
PMID- 28401294
TI - Drinking and water permeability in the Pacific hagfish, Eptatretus stoutii.
AB - Hagfish are osmoconformers, maintaining an internal osmolality that matches their
seawater habitats. Hagfish would, therefore, appear to have no physiological need
to drink, but previous studies are equivocal regarding whether drinking in
hagfish occurs. The current study addressed this knowledge gap, by examining
drinking and water permeability in the Pacific hagfish, Eptatretus stoutii. One
third of analysed hagfish were shown to accumulate radiolabelled drinking rate
markers (tritiated inulin and polyethylene glycol-4000) in their gut tissues;
however, this was attributed to the presence of markers in the blood perfusing
the digestive tract, following absorption through paracellular pathways at the
gill. No accumulation of marker was observed in hagfish subjected to more dilute
(75% seawater) or more concentrated (125% seawater) media. Diffusive water
efflux, measured by tritiated water washout, was shown to be very high, with 50%
of body water exchanged within 14 to 16 min, depending on exposure salinity. In
full-strength seawater, the total exchangeable pool of water was 78% of hagfish
mass. We conclude that hagfish do not drink, and their high water permeability is
likely to result in rapid osmotic equilibration under circumstances where
perturbations may occur.
PMID- 28401293
TI - How low can you go? An adaptive energetic framework for interpreting basal
metabolic rate variation in endotherms.
AB - Adaptive explanations for both high and low body mass-independent basal metabolic
rate (BMR) in endotherms are pervasive in evolutionary physiology, but arguments
implying a direct adaptive benefit of high BMR are troublesome from an energetic
standpoint. Here, we argue that conclusions about the adaptive benefit of BMR
need to be interpreted, first and foremost, in terms of energetics, with
particular attention to physiological traits on which natural selection is
directly acting. We further argue from an energetic perspective that selection
should always act to reduce BMR (i.e., maintenance costs) to the lowest level
possible under prevailing environmental or ecological demands, so that high BMR
per se is not directly adaptive. We emphasize the argument that high BMR arises
as a correlated response to direct selection on other physiological traits
associated with high ecological or environmental costs, such as daily energy
expenditure (DEE) or capacities for activity or thermogenesis. High BMR thus
represents elevated maintenance costs required to support energetically demanding
lifestyles, including living in harsh environments. BMR is generally low under
conditions of relaxed selection on energy demands for high metabolic capacities
(e.g., thermoregulation, activity) or conditions promoting energy conservation.
Under these conditions, we argue that selection can act directly to reduce BMR.
We contend that, as a general rule, BMR should always be as low as environmental
or ecological conditions permit, allowing energy to be allocated for other
functions. Studies addressing relative reaction norms and response times to
fluctuating environmental or ecological demands for BMR, DEE, and metabolic
capacities and the fitness consequences of variation in BMR and other metabolic
traits are needed to better delineate organismal metabolic responses to
environmental or ecological selective forces.
PMID- 28401295
TI - The metagenomics worldwide research.
AB - Metagenomics is the technique, or set of techniques, whose main objective is to
determine the microbial population that can be found in a determined environment,
studied in the context of its community. For this, it uses the techniques of
massive sequencing, or next generation sequencing, due to the difficulties
presented by traditional techniques when trying to transfer all the
microorganisms present in a given environment to the laboratory. Metagenomics is
a newly created technique, which was born at the beginning of the twenty-first
century, and since then the interest of the world scientific community in fields
as diverse as medicine, biotechnology, agriculture or genetics has not left to
grow. In this article, the authors make a historical review of the metagenomics,
analyze and evaluate the different massive sequencing platforms used for
metagenomic assays, review the current literature on this subject and advance
future problems with which researchers who decide to go deeper in this field
could find. In this way, the prior knowledge of the researcher will facilitate
the approach of his research.
PMID- 28401297
TI - Familial dysautonomia: a disease with hidden tears.
PMID- 28401296
TI - Associations of specific psychiatric disorders with isolated focal dystonia, and
monogenic and idiopathic Parkinson's disease.
AB - Comorbidity of psychiatric disorders in patients with movement disorders is
common. Often, psychiatric symptoms manifest before the onset of the movement
disorder, thus not representing a mere reaction to its burden. How the disease
mechanisms of psychiatric and movement disorders are related is still poorly
understood. The aim of the present study was to compare prevalence rates of
specific psychiatric disorders between different movement disorders including
isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N =
41), idiopathic PD (N = 45), and a sample from a Northern Germany general
population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of
2.6 [confidence interval (CI) 1.7-4.0] for general axis I disorders in IFD, an OR
of 2.5 (CI 1.4-4.7) in monogenic PD, and an OR of 1.4 (CI 0.8-2.6) in idiopathic
PD. More specifically, the monogenic PD group showed the highest ORs for
affective disorders including depression (OR = 4.9), bipolar disorder (OR =
17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest
rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in
the PD groups but not in IFD. Our findings underline the notion that psychiatric
disorders are part of the phenotypic spectrum of movement disorders. Moreover,
they suggest that IFD, monogenic PD, and idiopathic PD are associated with
specific psychiatric disorders indicating disturbances in a different neural
circuitry for sensorimotor control.
PMID- 28401298
TI - Neurovascular hand symptoms in relation to cold exposure in northern Sweden: a
population-based study.
AB - PURPOSE: To describe the self-reported ambient cold exposure in northern Sweden
and to relate the level of cumulative cold exposure to the occurrence of sensory
and vascular hand symptoms. We hypothesize that cold exposure is positively
related to reporting such symptoms. METHODS: A questionnaire about cold exposure
and related symptoms was sent out to 35,144 subjects aged 18-70 years and living
in northern Sweden. RESULTS: A total of 12,627 out of 35,144 subjects returned
the questionnaire (response rate 35.9%). Subjects living in the rural alpine
areas reported more extensive cold exposure both during work and leisure time
compared to the urbanized coastal regions. Frostbite in the hands was present in
11.4% of men and 7.1% of women, cold sensitivity was present in 9.7 and 14.4%,
and Raynaud's phenomenon was present in 11.0% of men and 14.0% of women. There
was a positive association between cumulative cold exposure and neurovascular
hand symptoms. CONCLUSION: The present study demonstrates that the cold
environment in northern Sweden might be an underestimated health risk. Our
hypothesis that cold exposure is positively related to reporting of neurovascular
hand symptoms was supported by our findings. In addition, such symptoms were
common not only in conjunction with an overt cold injury. Our results warrant
further study on pathophysiological mechanisms and suggest the need for
confirmatory prevalence studies to support national public health planning.
PMID- 28401299
TI - Minimally invasive endoscopic transcanal cartilage myringoplasty is the treatment
of choice for repair of anterosuperior perforations.
PMID- 28401300
TI - The role of thymectomy in the treatment of juvenile myasthenia gravis: a
systematic review.
AB - BACKGROUND: The role of thymectomy in the treatment of juvenile myasthenia gravis
(JMG) is poorly defined. The objective of this systematic review was to evaluate
the effect of thymectomy on survival, disease severity, and peri-operative
complications for patients with JMG. METHODS: A search of MEDLINE, EMBASE, and
the Cochrane Library (1/1/2000-3/1/2016) identified all English language, human
studies of thymectomy for JMG. The population was patients with JMG age <=18
years who underwent thymectomy (comparator group was unexposed to thymectomy).
Outcomes included survival, disease severity, and post-operative complications.
Data extraction was performed by independent reviewers. RESULTS: Sixteen
retrospective studies included 1131 participants with JMG and 488 (43%) underwent
thymectomy. Post-operative improvement in JMG severity occurred for 77% (n =
376/488). Comparisons of thymectomy to non-operative management were mixed. Post
operative complications were poorly recorded. Power to compare surgical
approaches was limited. Outcomes specific to antibodies, surgical pathology
findings, severity of JMG, and timing of thymectomy were sparse. CONCLUSIONS:
Existing data regarding thymectomy for JMG are limited and entirely
retrospective. The majority of patients who underwent thymectomy had improvement
in disease severity and post-operative complications were rare. Prospective,
multicenter study of thymectomy for JMG is warranted.
PMID- 28401301
TI - Enhancing dialyser clearance-from target to development.
AB - Products of metabolism accumulate in kidney failure and potentially have toxic
effects. Traditionally these uraemic toxins are classified as small, middle-sized
and protein-bound toxins, and clearance during dialysis is affected by diffusion,
convection and adsorption. As current dialysis practice effectively clears small
solutes, increasing evidence supports a toxic effect for middle-sized and protein
bound toxins. Therefore, newer approaches to standard dialysis practice are
required to look beyond urea clearance. Current dialysers have been developed to
effectively clear small solutes and secondly to increase middle-sized toxin
clearances. However, there is no ideal dialyser which can effectively clear all
uraemic toxins. Advances in nanotechnology have led to improvements in
manufacturing, with the production of smoother membrane surfaces and uniformity
of pore size. The introduction of haemodiafiltration has led to changes in
dialyser design to improve convective clearances. Both diffusional and
convectional clearances can be increased by changing dialyser designs to alter
blood and dialysate flows, and novel dialyser designs using microfluidics offer
more efficient solute clearances. Adjusting surface hydrophilicity and charge
alter adsorptive properties, and greater clearance of protein-bound toxins can be
achieved by adding carbon or other absorptive monoliths into the circuit or by
developing composite dialyser membranes. Other strategies to increase protein
bound toxins clearances have centred on disrupting binding and so displacing
toxins from proteins. Just as the hollow fibre design replaced the flat plate
dialyser, we are now entering a new era of dialyser designs aimed to increase the
spectrum of uraemic toxins which can be cleared by dialysis.
PMID- 28401302
TI - Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor
suppresses malignant glioma cell growth in vitro and in vivo by regulating the
PI3K/AKT signaling pathway.
AB - PURPOSE: Glioblastoma is a highly invasive and challenging tumor of the central
nervous system. The mutation/deletion of the tumor suppressor phosphatase and
tensin homolog (PTEN) gene is the main genetic change identified in
glioblastomas. PTEN plays a critical role in tumorigenesis and has been shown to
be an important therapeutic target. The phosphatidylinositol 3-kinase (PI3K)
inhibitor LY294002 is commonly used to inhibit glioma cell growth via regulation
of the PI3K/AKT signaling pathway. In this study, we examined the growth
inhibitory effects of a combinatorial therapy of adenoviral-mediated PTEN (Ad
PTEN) and LY294002 on LN229 and U251 glioma cells in vitro and on tumor
xenografts in vivo. METHODS: In vitro, LN229 and U251 glioma cells were treated
by combinatorial therapy with Ad-PTEN and LY294002. The growth ability was
determined by MTT assay. The cell cycle distribution was analyzed by flow
cytometry. Cell invasive ability was analyzed by transwell invasion assay and
cell apoptosis analysis via FITC-Annexin V analysis. In vivo, U251 subcutaneous
glioblastoma xenograft was used to assay anti-tumor effect of combinatorial
therapy with Ad-PTEN and LY294002 by mean volume of tumors, immunohistochemistry
and TUNEL method. RESULTS: The combinatorial treatment clearly suppressed cell
proliferation, arrested the cell cycle, reduced cell invasion and promoted cell
apoptosis compared with the Ad-PTEN or LY294002 treatment alone. The treatment
worked by inhibiting the PI3K/AKT pathway. In addition, the growth of U251 glioma
xenografts treated with the combination of Ad-PTEN and LY294002 was significantly
inhibited compared with those treated with Ad-PTEN or LY294002 alone.
CONCLUSIONS: Our data indicated that the combination of Ad-PTEN and LY294002
effectively suppressed the malignant growth of human glioma cells in vitro and in
tumor xenografts, suggesting a promising new approach for glioma gene therapy
that warrants further investigation.
PMID- 28401304
TI - Postmortem concentration distribution in fatal cases involving the synthetic
opioid U-47700.
PMID- 28401303
TI - Evaluation of forensic genetic parameters of 12 STR loci in the Korean population
using the InvestigatorR HDplex kit.
AB - We genotyped and calculated the forensic parameters of 10 non-CODIS loci and 2
CODIS loci of 990 Korean individuals using the InvestigatorR HDplex kit. No
significant deviations from Hardy-Weinberg equilibrium (after Bonferroni
correction for multiple testing) or genetic linkage disequilibrium were observed.
The calculated matching probability and power of discrimination ranged from
0.0080 to 0.2014, and 0.7986 to 0.9920, respectively. We conclude that the
markers of the kit are highly informative corroborative tools for forensic DNA
analysis.
PMID- 28401306
TI - Toolbox in a tadpole: Xenopus for kidney research.
AB - Xenopus is a versatile model organism increasingly used to study organogenesis
and genetic diseases. The rapid embryonic development, targeted injections, loss-
and gain-of-function experiments and an increasing supply of tools for functional
in vivo analysis are unique advantages of the Xenopus system. Here, we review the
vast array of methods available that have facilitated its transition into a
translational model. We will focus primarily on how these methods have been
employed in the study of kidney development, renal function and kidney disease.
Future advances in the fields of genome editing, imaging and quantitative 'omics
approaches are likely to enable exciting and novel applications for Xenopus to
deepen our understanding of core principles of renal development and molecular
mechanisms of human kidney disease. Thus, using Xenopus in clinically relevant
research diversifies the narrowing pool of "standard" model organisms and
provides unique opportunities for translational research.
PMID- 28401305
TI - Evaluation of specific neural marker GAP-43 and TH combined with Masson-trichrome
staining for forensic autopsy cases with old myocardial infarction.
AB - It has been a puzzling forensic task to determine the cause of death as a result
of old myocardial infarction (OMI) in the absence of recognizable acute
myocardial infarction. Recent studies indicated that the heterogeneous cardiac
nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted
site played important roles in sudden cardiac death (SCD). So, the present study
explored the value of growth associated protein-43 (GAP-43) and tyrosine
hydroxylase (TH) as objective and specific neural biomarkers combined with Masson
trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58
medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control
cases, were immunostained with anti-GAP-43 and anti-TH antibodies.
Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in
OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were
abundant at border zones of the infarcted site. There were a few GAP-43 and TH
expressions in the control cases. With Masson-trichrome staining, collagen fibers
were blue and cardiac muscle fibers were pink in marked contrast with the
surrounding tissue, which improved the location of nerve fibers. Thus, these
findings suggest that immunohistochemical detection of GAP-43 and TH combined
with Masson-trichrome staining can provide the evidence for the medicolegal
expertise of SCD due to OMI, and further demonstrate a close relationship between
sympathetic hyperinnervation and SCD.
PMID- 28401307
TI - Immunohistochemical mapping and transcript expression of the GPA2/GPB5 receptor
in tissues of the adult mosquito, Aedes aegypti.
AB - GPA2/GPB5 is a glycoprotein hormone found in most bilateral metazoans including
the mosquito, Aedes aegypti. To elucidate physiological roles and functions of
GPA2/GPB5, we aim to identify prospective target tissues by examining the tissue-
and sex-specific expression profile of its receptor, the leucine-rich repeat
containing G protein-coupled receptor 1 (LGR1) in the adult mosquito. Western
analyses using a heterologous system with CHO-K1 cells, transiently expressing A.
aegypti LGR1, yielded a 112-kDa monomeric band and high-molecular weight
multimers, which associated with membrane-protein fractions. Moreover, immunoblot
analyses on protein isolated from HEK 293 T cells stably expressing a fusion
construct of A. aegypti LGR1-EGFP (LGR1: 105 kDa+EGFP: 27 kDa) yielded a band
with a measured molecular weight of 139 kDa that also associated with membrane
protein fractions and upon deglycosylation, migrated as a lower molecular weight
band of 132 kDa. Immunocytochemical analysis of HEK 293 T cells stably expressing
this fusion construct confirmed EGFP fluorescence and LGR1-like immunoreactivity
colocalized primarily to the plasma membrane. Immunohistochemical mapping in
adult mosquitoes revealed LGR1-like immunoreactivity is widespread in the
alimentary canal. Importantly, LGR1-like immunoreactivity localizes specifically
to basolateral regions of epithelia and, in some regions, appeared as punctate
intracellular staining, which together indicates a potential role in feeding
and/or hydromineral balance. LGR1 transcript expression was also detected in gut
regions that exhibited strong LGR1-like immunoreactivity. Interestingly, LGR1
transcript expression and strong LGR1-like immunoreactivity was also identified
in reproductive tissues including the testes and ovaries, which together suggests
a potential role linked to spermatogenesis and oogenesis in male and female
mosquitoes, respectively.
PMID- 28401308
TI - Using Drosophila nephrocytes in genetic kidney disease.
AB - Renal diseases are a growing health burden, and innovative models to study their
pathomechanisms are greatly needed. Here, we highlight how the fruit fly
Drosophila melanogaster can be used to model kidney diseases. We focus on the
nephrocyte that has recently been shown to exhibit podocyte and proximal tubular
cell features. These cells can be manipulated with precise genetic tools to
dissect filtration and reabsorption mechanisms. Thus, they represent a novel and
easy-to-use alternative in experimental nephrology.
PMID- 28401309
TI - Pathomechanisms of renal Fabry disease.
PMID- 28401310
TI - The efficacy of periodised resistance training on neuromuscular adaptation in
older adults.
AB - PURPOSE: This study compared the effect of periodised versus non-periodised (NP)
resistance training on neuromuscular adaptions in older adults. METHODS: Forty
one apparently healthy untrained older adults (female = 21, male = 20; 70.9 +/-
5.1 years; 166.3 +/- 8.2 cm; 72.9 +/- 13.4 kg) were recruited and randomly
stratified to an NP, block periodised (BP), or daily undulating periodised (DUP)
training group. Outcome measures were assessed at baseline and following a 22
week resistance training intervention (3 day week-1), including: muscle cross
sectional area (CSA), vertical jump performance, isometric and isokinetic peak
torque, isometric rate of force development (RFD), and muscle activation. Thirty
three participants satisfied all study requirements and were included in analyses
(female = 17, male = 16; 71.3 +/- 5.4 years; 166.3 +/- 8.5 cm; 72.5 +/- 13.7 kg).
RESULTS: Block periodisation, DUP, and NP resistance training induced
statistically significant improvements in muscle CSA, vertical jump peak
velocity, peak power and jump height, and peak isometric and isokinetic torque of
the knee extensors at 60 and 180 degrees s-1, with no between-group differences.
Muscle activity and absolute RFD measures were statistically unchanged following
resistance training across the entire cohort. CONCLUSIONS: Periodised resistance
training, specifically BP and DUP, and NP resistance training are equally
effective for promoting increases in muscular hypertrophy, strength, and power
among untrained older adults. Consequently, periodisation strategies are not
essential for optimising neuromuscular adaptations during the initial stages of
resistance training in the aging population.
PMID- 28401311
TI - Development of site fidelity in the nocturnal amblypygid, Phrynus
marginemaculatus.
AB - Amblypygids are capable of navigation in the complex terrain of rainforests in
near complete darkness. Path integration is unnecessary for successful homing,
and the alternative mechanisms by which they navigate have yet to be elucidated.
Here, our aims were to determine whether the amblypygid Phrynus marginemaculatus
could be trained to reliably return to a target shelter in a laboratory arena
indicating goal recognition-and to document changes in behavior associated with
the development of fidelity. We recorded nocturnal movements and space use by
individuals over five nights in an arena in which subjects were provided with two
shelters that differed in quality. The target shelter, unlike the alternative
shelter, shielded subjects from light in daylight hours. Individuals consistently
exited and returned to a shelter each night and from the third night onward chose
the target shelter more often than the alternative shelter. Indeed, on the fifth
night, every subject chose the target shelter. This transition was associated
with changes in movement and space use in the arena. Notably, the movement
features of outbound and inbound paths differed but did not change across nights.
Individuals were also characterized by distinct behavioral strategies reflecting
candidate homing mechanisms.
PMID- 28401312
TI - Core curriculum illustration: anterior process fracture of the calcaneus.
AB - This is the 28th installment of a series that will highlight one case per
publication issue from the bank of cases available online as part of the American
Society of Emergency Radiology (ASER) educational resources. Our goal is to
generate more interest in and use of our online materials. To view more cases
online, please visit the ASER Core Curriculum and Recommendations for Study
online at http://www.aseronline.org/curriculum/toc.htm .
PMID- 28401313
TI - Erratum to: Symptom clusters during palliative chemotherapy and their influence
on functioning and quality of life.
PMID- 28401314
TI - The prognostic performance of adding patient-reported outcomes to the MASCC risk
index to identify low-risk febrile neutropenia patients with solid tumors and
lymphomas.
AB - PURPOSE: This study aims to develop and validate a prognostic model (PROMASCC) by
incorporating the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N)
elements, with the Multinational Association of Supportive Care in Cancer (MASCC)
risk index, for identifying low-risk patients with febrile neutropenia (FN) for
developing serious complications. METHODS: This was a single-center, cross
sectional observational study. Either English or Chinese versions of the FACT-N
were administered to the eligible patients according to their language preference
within 7 days of FN onset. Univariate analyses and multivariate analyses were
performed to construct the PROMASCC model. The prognostic performance was
compared between the PROMASCC model and MASCC risk index. The internal validation
of the PROMASCC model was examined by bootstrapping technique. RESULTS: From
August 2014 to April 2016, a total of 120 eligible patients were included in this
study. In the univariate analyses, only the malaise subscale score has been
significantly associated with the favorable outcome (without complications) (P =
0.024). Compared to the MASCC risk index, the PROMASCC model has shown advantages
on the improved specificity (64.3 vs. 38.1%) and positive predictive value (81.0
vs. 73.7%), lower misclassification rate (24.2 vs. 25.8%), and increased area
under receiver-operating characteristic curve (0.732 vs. 0.658). The
bootstrapping procedure estimates the optimism-corrected area for the PROMASCC
model to be 0.731 (95% CI 0.648 to 0.814). CONCLUSIONS: This study has developed
and validated a PROMASCC model and demonstrated that additional measurement on
patient's fatigue level could improve the risk stratification of patients with
FN.
PMID- 28401315
TI - Improving the 'tool box' for robust industrial enzymes.
AB - The speed of sequencing of microbial genomes and metagenomes is providing an ever
increasing resource for the identification of new robust biocatalysts with
industrial applications for many different aspects of industrial biotechnology.
Using 'natures catalysts' provides a sustainable approach to chemical synthesis
of fine chemicals, general chemicals such as surfactants and new consumer-based
materials such as biodegradable plastics. This provides a sustainable and 'green
chemistry' route to chemical synthesis which generates no toxic waste and is
environmentally friendly. In addition, enzymes can play important roles in other
applications such as carbon dioxide capture, breakdown of food and other waste
streams to provide a route to the concept of a 'circular economy' where nothing
is wasted. The use of improved bioinformatic approaches and the development of
new rapid enzyme activity screening methodology can provide an endless resource
for new robust industrial biocatalysts.This mini-review will discuss several
recent case studies where industrial enzymes of 'high priority' have been
identified and characterised. It will highlight specific hydrolase enzymes and
recent case studies which have been carried out within our group in Exeter.
PMID- 28401316
TI - The Orally Active Noncompetitive AMPAR Antagonist Perampanel Attenuates Focal
Cerebral Ischemia Injury in Rats.
AB - Inhibition of ionotropic glutamate receptors (iGluRs) is a potential target of
therapy for ischemic stroke. Perampanel is a potent noncompetitive alpha-amino-3
hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist with good
oral bioavailability and favorable pharmacokinetic properties. Here, we
investigated the potential protective effects of perampanel against focal
cerebral ischemia in a middle cerebral artery occlusion (MCAO) model in rats.
Oral administration with perampanel significantly reduced MCAO-induced brain
edema, brain infarct volume, and neuronal apoptosis. These protective effects
were associated with improved functional outcomes, as measured by foot-fault
test, adhesive removal test, and modified neurological severity score (mNSS)
test. Importantly, perampanel was effective even when the administration was
delayed to 1 h after reperfusion. The results of enzyme-linked immunosorbent
assay (ELISA) showed that perampanel significantly decreased the expression of
pro-inflammatory cytokines IL-1beta and TNF-alpha, whereas it increased the
levels of anti-inflammatory cytokines IL-10 and TGF-beta1 after MCAO. In
addition, perampanel treatment markedly decreased the expression of inducible
nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), and also
inhibited nitric oxide (NO) generation in MCAO-injured rats at 24 and 72 h after
reperfusion. In conclusion, this study demonstrated that the orally active AMPAR
antagonist perampanel protects against experimental ischemic stroke via
regulating inflammatory cytokines and NOS pathways.
PMID- 28401317
TI - Sexual Orientation-Related Differences in Virtual Spatial Navigation and Spatial
Search Strategies.
AB - Spatial abilities are generally hypothesized to differ between men and women, and
people with different sexual orientations. According to the cross-sex shift
hypothesis, gay men are hypothesized to perform in the direction of heterosexual
women and lesbian women in the direction of heterosexual men on cognitive tests.
This study investigated sexual orientation differences in spatial navigation and
strategy during a virtual Morris water maze task (VMWM). Forty-four heterosexual
men, 43 heterosexual women, 39 gay men, and 34 lesbian/bisexual women (aged 18-54
years) navigated a desktop VMWM and completed measures of intelligence,
handedness, and childhood gender nonconformity (CGN). We quantified spatial
learning (hidden platform trials), probe trial performance, and cued navigation
(visible platform trials). Spatial strategies during hidden and probe trials were
classified into visual scanning, landmark use, thigmotaxis/circling, and
enfilading. In general, heterosexual men scored better than women and gay men on
some spatial learning and probe trial measures and used more visual scan
strategies. However, some differences disappeared after controlling for age and
estimated IQ (e.g., in visual scanning heterosexual men differed from women but
not gay men). Heterosexual women did not differ from lesbian/bisexual women. For
both sexes, visual scanning predicted probe trial performance. More feminine CGN
scores were associated with lower performance among men and greater performance
among women on specific spatial learning or probe trial measures. These results
provide mixed evidence for the cross-sex shift hypothesis of sexual orientation
related differences in spatial cognition.
PMID- 28401318
TI - Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: its
clinical and angiographic perspectives.
AB - BACKGROUND: To assess the efficacy of stereotactic radiosurgery (SRS) for
intracranial dural arteriovenous fistulas (DAVFs), the authors retrospectively
reviewed our 7-year experience. We evaluated the obliteration rate, improvement
in clinical symptoms, and complications. METHODS: Thirty patients with DAVF
underwent SRS using a Gamma Knife between 2009 and 2015. Twenty-three patients
were treated with SRS alone, and seven patients underwent SRS for residual or
recurrent DAVFs after embolization or surgery. Chemosis, diplopia, and pulsating
tinnitus were the most common symptoms. Median target volume was 2.9 cm3 (range,
0.8-13.6 cm3), and median radiation dose to the target was 17 Gy (range, 12-20
Gy). Median follow-up period was 33 months (range, 6-82 months). RESULTS: At the
last neuroimaging follow-up, DAVFs were totally obliterated in 23 patients (77%)
and subtotally in 7 (23%). At the last clinical follow-up, 21 patients (70%)
showed complete recovery, and 9 (30%) showed incomplete recovery in symptoms or
signs. None experienced worsening symptoms or signs. Asymptomatic perilesional
edema after SRS occurred in one patient (3%). Total obliteration rates after SRS
were 43% at 1 year, 79% at 2 years, and 95% at 5 years. Improvement rates of
neurological function after SRS were 12% at 1 month, 52% at 2 months, 72% at 3
months, and 96% at 6 months. A multivariate analysis revealed that Borden type 1
(p = 0.019, hazard ratio, 3.254, 95% confidence interval, 1.216-8.707) was
significantly associated with symptom improvement. CONCLUSIONS: SRS for
intracranial DAVFs provided a high obliteration rate and a relatively low risk of
radiation-induced complications. In selected benign cases without cortical venous
drainage, SRS is a safe and effective treatment for symptom relief and fistula
obliteration, even though the time course of improvement is longer than those of
embolization and surgery.
PMID- 28401319
TI - Training charter in spasticity neurosurgery added competence.
PMID- 28401320
TI - The virulence factors of group A streptococcus strains isolated from invasive and
non-invasive infections in Polish and German centres, 2009-2011.
AB - Streptococcus pyogenes (GAS) is one of the major human pathogenic bacteria that
cause a wide range of diseases. Currently, increased incidence of streptococcal
invasive infections is observed worldwide. In this study, we focused on the
prevalence of genes encoding superantigens and type M proteins in the population
of GAS strains from invasive versus non-invasive infections. We tested 253 GAS
strains: 48 strains from patients with invasive infections (18 from wound/deep
skin localization, 30 from women in labour) and 205 strains from non-invasive
forms (147 from common infections of the upper respiratory, 49 from the vagina of
females with genital tract infections and 9 from non-invasive wound and
superficial skin infections). Significant differences were found in the
occurrence of genes: speG, speI, speJ and smeZ, which were more common in GAS
isolated from invasive than from non-invasive strains; speJ and smeZ occurred
more frequently in strains from invasive perinatal infections versus strains from
women without symptoms of invasive infection; speH and speI in strains from
invasive skin/wound infection versus strains isolated from non-invasive wound and
superficial skin infections. Emm types 1 and 12 predominated in the group of
strains isolated from superficial infections and type 28 in those from puerperal
fever. Occurrence of genes encoding virulence factors is common in genomic DNA of
most of S. pyogenes, regardless whether these streptococcal infections are
invasive or non-invasive. On the other hand, it appears that strains with speG,
speI, speJ and smeZ genes may have a particular potential for virulence.
PMID- 28401321
TI - Circulating genotypes of Pneumocystis jirovecii and its clinical correlation in
patients from a single tertiary center in India.
AB - The present study was carried out with the objectives of genotyping Pneumocystis
jirovecii at three distinct loci, to identify the single nucleotide polymorphisms
(SNPs), and to study its clinical implications in patients with Pneumocystis
pneumonia (PCP). Analysis of genetic diversity in P. jirovecii from
immunocompromised patients was carried out by genotyping at three distinct loci
encoding mitochondrial large subunit rRNA (mtLSU rRNA), cytochrome b (CYB), and
superoxide dismutase (SOD) using polymerase chain reaction (PCR) assays followed
by direct DNA sequencing. Of the 300 patients enrolled in the present study, 31
(10.33%) were positive for PCP by a specific mtLSU rRNA nested PCR assay, whereas
only 15 P. jirovecii could be amplified at the other two loci (SOD and CYB).
These positives were further subjected to sequence typing. Important genotypic
combinations between four SNPs (mt85, SOD110, SOD215, and CYB838) and clinical
outcomes could be observed in the present study, and mt85A, mt85T, and
SOD110C/SOD215T were frequently associated with "negative follow-up". These SNPs
were also noted to be relatively more prevalent amongst circulating genotypes in
our study population. The present study is the first of its kind from the Indian
subcontinent and demonstrated that potential SNPs of P. jirovecii may possibly be
attributed to the clinical outcome of PCP episodes in terms of severity or
fatality in different susceptible populations likely to develop PCP during their
course of illness.
PMID- 28401322
TI - Biomass and nutrient allocation strategies in a desert ecosystem in the Hexi
Corridor, northwest China.
AB - The allocation of biomass and nutrients in plants is a crucial factor in
understanding the process of plant structures and dynamics to different
environmental conditions. In this study, we present a comprehensive scaling
analysis of data from a desert ecosystem to determine biomass and nutrient
(carbon (C), nitrogen (N), and phosphorus (P)) allocation strategies of desert
plants from 40 sites in the Hexi Corridor. We found that the biomass and levels
of C, N, and P storage were higher in shoots than in roots. Roots biomass and
nutrient storage were concentrated at a soil depth of 0-30 cm. Scaling
relationships of biomass, C storage, and P storage between shoots and roots were
isometric, but that of N storage was allometric. Results of a redundancy analysis
(RDA) showed that soil nutrient densities were the primary factors influencing
biomass and nutrient allocation, accounting for 94.5% of the explained
proportion. However, mean annual precipitation was the primary factor influencing
the roots biomass/shoots biomass (R/S) ratio. Furthermore, Pearson's correlations
and regression analyses demonstrated that although the biomass and nutrients that
associated with functional traits primarily depended on soil conditions, mean
annual precipitation and mean annual temperature had greater effects on roots
biomass and nutrient storage.
PMID- 28401323
TI - Exploring single nucleotide polymorphisms previously related to obesity and
metabolic traits in pediatric-onset type 2 diabetes.
AB - AIMS: To evaluate the association of 64 obesity-related polymorphisms with
pediatric-onset type 2 diabetes and other glucose- and insulin-related traits in
Mexican children. METHODS: Case-control and case-sibling designs were followed.
We studied 99 patients with pediatric-onset type 2 diabetes, their siblings (n =
101) without diabetes, 83 unrelated pediatric controls and 137 adult controls.
Genotypes were determined for 64 single nucleotide polymorphisms, and a possible
association was examined between those genotypes and type 2 diabetes and other
quantitative traits, after adjusting for age, sex and body mass index. RESULTS:
In the case-pediatric control and case-adult control analyses, five polymorphisms
were associated with increased likelihood of pediatric-onset type 2 diabetes;
only one of these polymorphisms (CADM2/rs1307880) also showed a consistent effect
in the case-sibling analysis. The associations in the combined analysis were as
follows: ADORA1/rs903361 (OR 1.9, 95% CI 1.2; 3.0); CADM2/rs13078807 (OR 2.2, 95%
CI 1.2; 4.0); GNPDA2/rs10938397 (OR 2.2, 95% CI 1.4; 3.7); VEGFA/rs6905288 (OR
1.4, 95% CI 1.1; 2.1) and FTO/rs9939609 (OR 1.8, 95% CI 1.0; 3.2). We also
identified 16 polymorphisms nominally associated with quantitative traits in
participants without diabetes. CONCLUSIONS: ADORA/rs903361, CADM2/rs13078807,
GNPDA2/rs10938397, VEGFA/rs6905288 and FTO/rs9939609 are associated with an
increased risk of pediatric-onset type 2 diabetes in the Mexican population.
PMID- 28401324
TI - Testing a Higher Order Model of Internalizing and Externalizing Behavior: The
Role of Aggression Subtypes.
AB - This study assessed how the forms and functions of aggression fit into a higher
order model of internalizing and externalizing behavior, for children in early
childhood (N = 332, M age = 47.11 months, SD = 7.32). The lower order
internalizing factors were depressed affect, anxious-fearfulness, and asocial
behavior (i.e., social withdrawal) and the lower order externalizing factors were
deception and hyperactivity. The forms and functions of aggression were crossed
to create four factors: reactive relational, reactive physical, proactive
relational, and proactive physical aggression. Seven confirmatory factor models
were tested. Results supported a two-factor externalizing model where reactive
and proactive relational aggression and deception loaded on one externalizing
factor and reactive and proactive physical aggression and hyperactivity loaded on
another externalizing factor.
PMID- 28401325
TI - Publication ethics: science versus commerce.
PMID- 28401326
TI - Clinical judgment, moral anxiety, and the limits of psychiatry.
AB - It is common for clinicians working in psychiatry and related clinical
disciplines to be called on to make diagnostic clinical judgments concerning
moral anxiety, which is a kind of anxiety that is closely bound up with decisions
individuals face as moral agents. To make such a judgment, it is necessary to
make a moral judgment. Although it has been common to acknowledge that there are
ways in which moral and clinical judgment interact, this type of interaction has
remained unacknowledged. This raises questions as to the nature and limits of
psychiatry-particularly concerning the extent to which psychiatric discourse
ought to incorporate moral discourse, and the role of the clinician as an expert
in identifying problematic anxiety.
PMID- 28401327
TI - Pulmonary embolism response teams.
AB - Pulmonary embolism (PE) is a common thrombotic event that is variable in its
presentation. Depending on the patients' risk for mortality, guidelines provide
several treatment strategies including thrombolysis, catheter-directed therapies,
pulmonary embolectomy, anticoagulation, and inferior vena cava filters. However,
there is considerable disagreement between guidelines regarding the optimal
treatment strategy for patients, particularly for those with intermediate-risk
PE. In order to provide rapid and individualized care, PE response teams (PERT)
have been developed. These teams consist of members from different specialties
with a particular interest in PE, varying technical skills, and clinical
experience, thereby allowing for a multidisciplinary approach. PERT allows for
consensus decision making, and for rapid intervention in patients whose
conditions worsen. In this review, we provide an overview of treatment guidelines
for PE, and of results from recent clinical trials involving patients with
submassive PE. In addition, we discuss an outline of our approach and use of
PERT.
PMID- 28401328
TI - Equine colic: clinical epidemiology and associated risk factors in and around
Debre Zeit.
AB - A prospective study was conducted to describe clinical epidemiology of equine
colic in the Society for Protection of Animal Abroad and Donkey Sanctuary Project
Clinic, at Debre Zeit, Ethiopia, from November 2014 to April 2015. The objectives
were to describe clinical epidemiology of equine colic, to characterize the main
types of equine colic, and to determine the major risk factors associated with
equine colic. The method which was used in the study was attending clinical case
of equine and assessing physiological parameters, fecal egg count, abdominal
sounds, and rectal examination as well as questioner interviewing of the owners.
The data were collected and analyzed using Statistical Package for Social
Science. The incidence of colic was 10.3% in the study period. Colicky were typed
as unknown, flatulent, impaction, spasmodic, and enterolithiasis. The proportion
of case incidence were 63.1 (41/65), 33.8 (22/65), and 3.1% (2/65), in donkey,
horse, and mule, respectively. The total mean (+/-SD) of temperature 37.80 +/-
1.003, heart rate 57.54 +/- 10.098, fecal egg count 236.922 +/- 67.990,
respiratory rate 30.92 +/- 7.315, and packed cell volume 41.40 +/- 10.221 were
recorded. The case fatality rate of equine colic was 15.38% (10/65). There were
statistically highly significant (p < 0.01) differences in impaction colic in
relation to species. Interview with 183 equine owners revealed incidence of
equine colic as the sixth major disease condition affecting equine. A long-term
epidemiological study of the true representative population should be carried out
to determine the incidence rate and associated risk factors of equine colic in
the study area.
PMID- 28401329
TI - Interactive effects of dietary leucine and isoleucine on growth, blood
parameters, and amino acid profile of Japanese flounder Paralichthys olivaceus.
AB - A 60-day feeding trial was conducted to assess the interactions of dietary
leucine (Leu) and isoleucine (Ile) on Japanese flounder. Fish of 2.69 +/- 0.04 g
were fed experimental diets containing two levels of Leu (2.58 and 5.08% of diet)
combined with three levels of Ile (1.44, 2.21, and 4.44% of diet), respectively.
After the feeding trial, growth, proximate composition, muscle total amino acid
profile, blood parameters, mucus lysozyme activity, and stress tolerance to
freshwater were measured. Statistically significant (P < 0.05) interactive
effects of Leu and Ile were found on growth parameters (final body weight, body
weight gain, and special growth rate) of Japanese flounder. Antagonism was
discovered in high dietary Leu groups, while stimulatory effects were obtained
for increased dietary Ile in low Leu groups. Interactive effects of these two
branched-chain amino acids were also found on hepatosomatic index of test fish.
In addition, crude lipid content of fish whole body was significantly altered by
various diets, with antagonism observed in low dietary Leu groups. Interactive
effects also existed in muscle amino acid profiles for low fish meal diets, but
no interactive impacts were observed on blood parameters. Furthermore, lysozyme
activities and freshwater stress were significantly affected by different diets.
And antagonism was found on lysozyme activities in low Leu groups. Moreover, high
Leu and high Ile levels of diet significantly altered freshwater stress tolerance
of Japanese flounder. These findings suggested that dietary Leu and Ile can
effect interactively, and fish fed with diets containing 2.58% Leu with 4.44% Ile
and 5.08% Leu with 1.44% Ile showed better growth performance.
PMID- 28401331
TI - Now is the Time for Psychology to Support the Transformation of Academic Health
Centers.
AB - Psychologists have made important contributions in academic health centers (AHC),
but the reputation of psychology as a discipline has been mixed, by turns viewed
as a superfluous soft science, or seen as an important contributor to the AHC
mission. AHCs currently face exceptional challenges to the viability of AHCs,
including: planned alterations from fee-for-service to value-based funding that
requires high quality at lower cost; and rising demands to demonstrate competence
in trainees. Now more than ever, psychologists can and must help AHCs to meet
these challenges.
PMID- 28401330
TI - Cordycepin confers neuroprotection in mice models of intracerebral hemorrhage via
suppressing NLRP3 inflammasome activation.
AB - Neuroinflammation has been recognized as a major contributor to brain injury
caused by intracerebral hemorrhage (ICH). Nucleotide-binding oligomerization
domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts
as an important mediator of inflammatory response in various inflammation-related
diseases including hemorrhagic insults. Cordycepin has recently been shown to
possess anti-inflammatory effect; however, its role and the possible underlying
mechanisms in ICH remain unclear. This study was designed to investigate the
neuroprotective effect of cordycepin in mice models of ICH and to elucidate the
underlying molecular mechanisms. ICH was induced in male ICR mice by injecting
autologous blood infusion stereotactically. Cordycepin was then given
intraperitoneally (i.p.) at 30 min after ICH induction. The results demonstrated
that NLRP3 inflammasome was activated and exacerbated the inflammatory
progression after ICH. Cordycepin treatment significantly alleviated neurological
deficits, brain edema, and perihematomal tissue damage following ICH. These
changes were accompanied by downregulated NLRP3 inflammasome components
expression and a reduction of production and release of inflammasome substrates
interleukin-1beta (IL-1beta) and interleukin-18 (IL-18). Furthermore, cordycepin
ameliorated neuronal death in the perihematomal regions, accompanied by a large
reduction in the expression of high-mobility group protein B 1 (HMGB1) post-ICH.
In conclusion, this study provides in vivo evidence that cordycepin confers
neuroprotective effect in the models of ICH, possibly through the suppression of
NLRP3 inflammasome activation.
PMID- 28401332
TI - A Method for Microalgae Proteomics Analysis Based on Modified Filter-Aided Sample
Preparation.
AB - With the fast development of microalgal biofuel researches, the proteomics
studies of microalgae increased quickly. A filter-aided sample preparation (FASP)
method is widely used proteomics sample preparation method since 2009. Here, a
method of microalgae proteomics analysis based on modified filter-aided sample
preparation (mFASP) was described to meet the characteristics of microalgae cells
and eliminate the error caused by over-alkylation. Using Chlamydomonas
reinhardtii as the model, the prepared sample was tested by standard LC-MS/MS and
compared with the previous reports. The results showed mFASP is suitable for most
of occasions of microalgae proteomics studies.
PMID- 28401334
TI - H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and
prognostically distinct subtypes with associated oncogenic drivers.
AB - Pediatric glioblastoma (pedGBM) is an extremely aggressive pediatric brain tumor,
accounting for ~6% of all central nervous system neoplasms in children.
Approximately half of pedGBM harbor recurrent somatic mutations in histone 3
variants or, infrequently, IDH1/2. The remaining subset of pedGBM is highly
heterogeneous, and displays a variety of genomic and epigenetic features. In the
current study, we aimed to further stratify an H3-/IDH-wild type (wt) pedGBM
cohort assessed through genome-wide molecular profiling. As a result, we
identified three molecular subtypes of these tumors, differing in their genomic
and epigenetic signatures as well as in their clinical behavior. We designated
these subtypes 'pedGBM_MYCN' (enriched for MYCN amplification), 'pedGBM_RTK1'
(enriched for PDGFRA amplification) and 'pedGBM_RTK2' (enriched for EGFR
amplification). These molecular subtypes were associated with significantly
different outcomes, i.e. pedGBM_RTK2 tumors show a significantly longer survival
time (median OS 44 months), pedGBM_MYCN display extremely poor outcomes (median
OS 14 months), and pedGBM_RTK1 tumors harbor an intermediate prognosis. In
addition, the various molecular subtypes of H3-/IDH-wt pedGBM were clearly
distinguishable from their adult counterparts, underlining their biological
distinctiveness. In conclusion, our study demonstrates significant molecular
heterogeneity of H3-/IDH-wt pedGBM in terms of DNA methylation and cytogenetic
alterations. The recognition of three molecular subtypes of H3-/IDH-wt pedGBM
further revealed close correlations with biological parameters and clinical
outcomes and may therefore, be predictive of response to standard treatment
protocols, but could also be useful for stratification for novel, molecularly
based therapies.
PMID- 28401335
TI - Fatal bronchovascular fistula after lobectomy visualized through postmortem
computed tomography angiography: A case report.
AB - False aneurysm of the pulmonary artery complicated by bronchovascular fistula
formation represents a rare life threating condition. We report a case of fatal
hemoptysis after formation of a bronchial fistula in the late postoperative
period after sleeve lobectomy. Cause of death was determined by external
postmortem examination, post mortem computed tomography (PMCT) and angiography
(PMCTA) without conventional autopsy.
PMID- 28401333
TI - Interactions of pathological proteins in neurodegenerative diseases.
AB - Neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal lobar
degeneration (FTD), Lewy body disease (LBD), Parkinson's disease (PD), and
amyotrophic lateral sclerosis (ALS) have in common that protein aggregates
represent pathological hallmark lesions. Amyloid beta-protein, tau-protein, alpha
synuclein, and TDP-43 are the most frequently aggregated proteins in these
disorders. Although they are assumed to form disease-characteristic aggregates,
such as amyloid plaques and neurofibrillary tangles in AD or Lewy bodies in
LBD/PD, they are not restricted to these clinical presentations. They also occur
in non-diseased individuals and can co-exist in the same brain without or with a
clinical picture of a distinct dementing or movement disorder. In this review, we
discuss the co-existence of these pathologies and potential additive effects in
the human brain as well as related functional findings on cross-seeding and
molecular interactions between these aggregates/proteins. We conclude that there
is evidence for interactions at the molecular level as well as for additive
effects on brain damage by multiple pathologies occurring in different
functionally important neurons. Based upon this information, we hypothesize a
cascade of events that may explain general mechanisms in the development of
neurodegenerative disorders: (1) distinct lesions are a prerequisite for the
development of a distinct disease (e.g., primary age-related tauopathy for AD),
(2) disease-specific pathogenic events further trigger the development of a
specific disease (e.g., Abeta aggregation in AD that exaggerate further Abeta and
AD-related tau pathology), (3) the symptomatic disease manifests, and (4)
neurodegenerative co-pathologies may be either purely coincidental or (more
likely) have influence on the disease development and/or its clinical
presentation.
PMID- 28401336
TI - Genome-wide identification and characterization of NB-ARC resistant genes in
wheat (Triticum aestivum L.) and their expression during leaf rust infection.
AB - KEY MESSAGE: NB-ARC domain-containing resistance genes from the wheat genome were
identified, characterized and localized on chromosome arms that displayed
differential yet positive response during incompatible and compatible leaf rust
interactions. Wheat (Triticum aestivum L.) is an important cereal crop; however,
its production is affected severely by numerous diseases including rusts. An
efficient, cost-effective and ecologically viable approach to control pathogens
is through host resistance. In wheat, high numbers of resistance loci are present
but only few have been identified and cloned. A comprehensive analysis of the NB
ARC-containing genes in complete wheat genome was accomplished in this study.
Complete NB-ARC encoding genes were mined from the Ensembl Plants database to
predict 604 NB-ARC containing sequences using the HMM approach. Genome-wide
analysis of orthologous clusters in the NB-ARC-containing sequences of wheat and
other members of the Poaceae family revealed maximum homology with Oryza sativa
indica and Brachypodium distachyon. The identification of overlap between
orthologous clusters enabled the elucidation of the function and evolution of
resistance proteins. The distributions of the NB-ARC domain-containing sequences
were found to be balanced among the three wheat sub-genomes. Wheat chromosome
arms 4AL and 7BL had the most NB-ARC domain-containing contigs. The spatio
temporal expression profiling studies exemplified the positive role of these
genes in resistant and susceptible wheat plants during incompatible and
compatible interaction in response to the leaf rust pathogen Puccinia triticina.
Two NB-ARC domain-containing sequences were modelled in silico, cloned and
sequenced to analyze their fine structures. The data obtained in this study will
augment isolation, characterization and application NB-ARC resistance genes in
marker-assisted selection based breeding programs for improving rust resistance
in wheat.
PMID- 28401337
TI - RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing
of a specific set of genes.
AB - KEY MESSAGE: The RNA recognition motif of Arabidopsis splicing factor SF1 affects
the alternative splicing of FLOWERING LOCUS M pre-mRNA and a heat shock
transcription factor HsfA2 pre-mRNA. Splicing factor 1 (SF1) plays a crucial role
in 3' splice site recognition by binding directly to the intron branch point.
Although plant SF1 proteins possess an RNA recognition motif (RRM) domain that is
absent in its fungal and metazoan counterparts, the role of the RRM domain in SF1
function has not been characterized. Here, we show that the RRM domain
differentially affects the full function of the Arabidopsis thaliana AtSF1
protein under different experimental conditions. For example, the deletion of RRM
domain influences AtSF1-mediated control of flowering time, but not the abscisic
acid sensitivity response during seed germination. The alternative splicing of
FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found
that the RRM domain of AtSF1 protein alters the production of alternatively
spliced FLM-beta transcripts. We also found that the RRM domain affects the
alternative splicing of a heat shock transcription factor HsfA2 pre-mRNA, thereby
mediating the heat stress response. Taken together, our results suggest the
importance of RRM domain for AtSF1-mediated alternative splicing of a subset of
genes involved in the regulation of flowering and adaptation to heat stress.
PMID- 28401338
TI - Serum HE4 is correlated to prognostic factors and survival in patients with
endometrial cancer.
AB - The extent of surgery and the decision for adjuvant treatment in patients with
endometrial cancer (EC) depend on the presence of risk factors for lymph node
metastases and disease recurrence. Postoperative markers such as myometrial
infiltration and specific mutations can select patients for adjuvant treatment
but will not influence surgical planning. A biomarker stratifying patients into
low-risk and high-risk groups before surgery could identify patients who benefit
from more extensive surgery. Therefore, we evaluated the correlation of serum
biomarker HE4 with clinical and recently identified prognostic pathological
variables and survival. Patients treated for endometrial cancer between 1994 and
2014 were included. Serum HE4 concentration was measured in preoperatively
obtained samples. A total of 88 patients were eligible for analysis. The majority
(64%) was diagnosed with endometrioid-type adenocarcinoma. Serum HE4
concentration is significantly associated with stage of disease (p = 0.001), deep
myometrial invasion (p < 0.001), exact depth of myometrial invasion (>=4 mm) (p =
0.01), tumour-free distance to serosa (<=7 mm) (p < 0.001), extensive lymph
vascular space invasion (p = 0.04) and cervical involvement (p = 0.001). HE4
concentration and nodal involvement were correlated, although not significant (p
= 0.17). Serum HE4 is an independent prognostic factor for recurrence-free
survival (HR 5.12 per 10-fold increase in HE4, 95% CI 1.54-17.1) and overall
survival (HR 7.48 per 10-fold increase in HE4, 95% CI 1.76-31.7). HE4 is a
prognostic marker in endometrial cancer and is helpful in addition to other
variables for the preoperative risk stratification of patients with endometrial
cancer.
PMID- 28401339
TI - Evaluation of the R2* value in invasive ductal carcinoma with respect to hypoxic
related prognostic factors using iterative decomposition of water and fat with
echo asymmetry and least-squares emission (IDEAL).
AB - OBJECTIVE: To correlate the R2* value obtained by iterative decomposition of
water and fat with echo asymmetry and least-squares emission (IDEAL) with
fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1alpha) in
breast carcinoma. METHODS: Forty-two patients who were diagnosed with invasive
ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before
surgery. The entire region of interest (ROI) was delineated on the R2* map, and
average tumour R2* value was calculated for each ROI. Histological specimens were
evaluated for the presence of FF, the microvessel density (the average
microvessel density and the ratio of peripheral to central microvessel density),
and the grading of HIF-1alpha. RESULTS: FF was identified in 47.6% (20/42) of
IDCs. Average R2* value for IDC with FF (42.4+/-13.2 Hz) was significantly higher
than that without FF (28.5+/-13.9 Hz) (P = 0.01). Spearman rank correlation
suggested that the average R2* value correlated with the grade of HIF-1alpha and
the ratio of peripheral to central microvessel density for IDCs (P < 0.001).
CONCLUSION: Quantification of tumour R2* using IDEAL is associated with the
presence of FF and the overexpression of HIF-1alpha, and may therefore be useful
in predicting hypoxia of breast carcinoma. KEY POINTS: * R2* value obtained by
IDEAL correlates with the overexpression of HIF-1alpha. * R2* value obtained by
IDEAL is associated with fibrotic focus. * R2* quantification may be useful in
predicting hypoxia of breast carcinoma.
PMID- 28401340
TI - Seizure threshold increases can be predicted by EEG quality in right unilateral
ultrabrief ECT.
AB - Increases in seizure threshold (ST) over a course of brief pulse ECT can be
predicted by decreases in EEG quality, informing ECT dose adjustment to maintain
adequate supra-threshold dosing. ST increases also occur over a course of right
unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between
ST increases and EEG indices. This study (n = 35) investigated if increases in ST
over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST
titration was performed at ECT session one and seven, with treatment dosing
maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality
indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post
ictal suppression) were manually rated at the first supra-threshold treatment,
and last supra-threshold treatment before re-titration, using a structured rating
scale, by a single trained rater blinded to the ECT session being rated. Twenty
one subjects (60%) had a ST increase. The association between ST changes and EEG
quality indices was analysed by logistic regression, yielding a significant model
(p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude
(p < 0.05) were significant predictors of change in ST. Percentage change in post
ictal suppression reached trend level significance (p = 0.065). Increases in ST
over a RUL UB ECT course may be predicted by decreases in seizure quality,
specifically decline in mid-ictal amplitude and potentially in post-ictal
suppression. Such EEG indices may be able to inform when dose adjustments are
necessary to maintain adequate supra-threshold dosing in RUL UB ECT.
PMID- 28401341
TI - Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a
Higher Rate of Periprosthetic Infection Than Cefazolin.
AB - BACKGROUND: In total joint arthroplasty (TJA), vancomycin is used as
perioperative antibiotic prophylaxis in patients with penicillin allergy or in
patients colonized with methicillin-resistant Staphylococcus aureus (MRSA).
Although vancomycin dosing should be weight-based (15 mg/kg), not all surgeons
are aware of this; a fixed 1-g dose is instead frequently administered.
QUESTIONS/PURPOSES: (1) Is there a difference in the risk of periprosthetic joint
infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after
primary TJA? (2) What proportion of patients is adequately dosed with vancomycin?
(3) Compared with actual fixed dosing, does weight-based dosing result in a
greater proportion of patients staying above the recommended 15-mg/L level at the
beginning and end of surgery? (4) Are patients overdosed with vancomycin at
greater risk of developing nephrotoxicity and acute kidney injury? METHODS: A
single-institution, retrospective study was performed on 1828 patients undergoing
primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During
the same period, 5810 patients underwent primary TJA and received cefazolin
monotherapy. A chart review was performed to obtain patient characteristics,
antibiotic dose and timing of administration, and microbiology data. Adequate
vancomycin dosing was defined as 15 mg/kg and within the 125-mg range. Vancomycin
levels were calculated at the beginning and end of surgery using pharmacokinetic
equations. Levels of 15 mg/L were considered adequate. Logistic regression, chi
square tests, and analysis of variance were performed. RESULTS: Among primary
TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 [2%])
compared with patients receiving cefazolin prophylaxis (62 of 5810 [1%]; adjusted
odds ratio, 1.587 [1.004-2.508]; p = 0.048). Ten percent of PJIs in the
vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with
adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all
procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was
adequately dosed according to weight-based dosage recommendations. Furthermore,
94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom
64% (1105 of 1726) were underdosed. All patients had vancomycin infusion
initiated within 2 hours before incision. A weight-based protocol would have
resulted in fewer patients having unacceptably low vancomycin levels (< 15 mg/L)
compared with those with actual fixed dosing, both for the beginning of surgery
at the time of incision (zero of 1828 [0%] versus 471 of 1828 [26%]; odds ratio,
0.001 [0.000-0.013]; p < 0.001) and at the end of surgery (33 of 1828 [2%] versus
746 of 1828 [41%]; odds ratio, 0.027 [0.019-0.038]; p < 0.001). Between the
vancomycin dosage groups, there were no differences in the rate of nephrotoxicity
(underdosed: 12 of 1130 [1%], adequately dosed: five of 518 [1%], overdosed: four
of 180 [2%], p = 0.363) and acute kidney injury (underdosed: 28 of 1130 [2%],
adequately dosed: 10 of 518 [2%], overdosed: six of 180 [3%], p = 0.561).
CONCLUSIONS: The majority of patients given vancomycin prophylaxis are underdosed
according to the weight-based dosage recommendations, and MRSA did not occur in
patients who were adequately dosed with vancomycin. Surgeons should thus ensure
that their patients are adequately dosed with vancomycin using the recommendation
of 15 mg/kg and that the dose of vancomycin is administered in a timely fashion.
Furthermore, and based on the findings of this study, we have moved toward
limiting the utilization of vancomycin prophylaxis for patients undergoing
elective arthroplasty at our institution. LEVEL OF EVIDENCE: Level III,
therapeutic study.
PMID- 28401343
TI - Erratum to: Palatable food consumption in children: interplay between (food)
reward motivation and the home food environment.
PMID- 28401342
TI - Tuberculosis in children with sickle cell anaemia: a retrospective study in
French tertiary care centres.
AB - : Tuberculosis (TB) and sickle cell anaemia (SCA) may affect the same population
of patients, particularly in Africa but also in high-TB incidence areas in
developed countries. However, few data are available from children with SCA who
develop TB. The aim of this study was to describe the clinical features and
outcome of TB diagnosed in children with SCA. We conducted a retrospective,
descriptive study in three referral centre of Sickle Cell Disease in Paris,
France. We included 11 patients with SCA who develop TB. The median age at TB
diagnosis was 11 years [7.5-14.5]. Two patients were asymptomatic and nine
patients were symptomatic. Six patients had pulmonary TB (pulmonary, pleural and
mediastinal lesions). Five patients had extrapulmonary TB (osteoarticular TB,
hepatic TB, cervical and mediastinal TB). Mycobacterium tuberculosis was isolated
in four of the 11 cases. All patients recovered after a median of 6 months of
anti-TB treatment. The localisation of TB and outcome after treatment in our SCA
patients were similar to the one observed in an age-and sex-matched control group
of non-SCA patient with TB. CONCLUSION: despite the low number of patients
included in our study, SCA does not seem to be a risk factor for severe TB. What
is Known: * Tuberculosis (TB) remains a global health problem particularly in
developing countries, and Sickle cell anaemia (SCA) is currently one of the most
common genetic diseases in the world that mainly affects African populations. *
Very few data are available on TB in SCA patients. What is New: * The features of
TB in children with SCA seem to be comparable to those expected in general
population, with favourable outcomes in response to standard treatment. *
Monitoring the dosage of anti-TB treatments could be of interest because of the
possible impact of SCA on drug metabolism.
PMID- 28401344
TI - Transanal irrigation is effective in functional fecal incontinence.
AB - : Functional fecal incontinence (FFI) is divided into cases related to functional
constipation (FC) and cases without concomitant constipation termed functional
non-retentive fecal incontinence (FNRFI). Transanal irrigation (TAI) is widely
used in children with neurogenic fecal incontinence but is less studied in
children with functional defecation disorders. The aim was to evaluate the
feasibility and efficacy of TAI in the treatment of FFI. A retrospective study in
72 children (mean age 9.2 +/- 2.2 years, 47 males) with treatment-resistant FFI
was performed. All children accepted treatment and 35% (n = 25) were titrated to
daily sessions. Of the 63 children who fulfilled the Rome III criteria of
constipation, 46 (73%) showed full response with complete remission of
incontinence episodes. Eleven (17%) showed partial response (>=50% reduction). Of
nine children with FNRFI, four (44%) showed full response whereas two (22%)
showed partial response. We found no significant difference in the reduction of
incontinence episodes between the children with FC (87%) and children with FNRFI
(68%) (p = 0.11). CONCLUSION: TAI is an effective, well-tolerated, and safe
choice in children with FC. No clinical parameters seemed to predict response to
treatment. The number of children with FNRFI was low, but TAI seemed effective in
this group of children. What is Known: * Functional fecal incontinence (FFI) is a
frequent, chronic condition with significant impact on children's quality of
life. * Transanal irrigation (TAI) is used in children with neurogenic bowel
dysfunction but less studied in children with functional defecation disorders.
What is New: * TAI seems an effective, well-tolerated, and safe choice in
children with FFI due to functional constipation. * Albeit the number of children
with functional non-retentive fecal incontinence was low in our study, TAI seems
effective also in this group of children.
PMID- 28401345
TI - Vitamin D in European children-statement from the European Academy of Paediatrics
(EAP).
AB - Vitamin D is synthesized in human skin upon sun exposure and is also a nutrient.
It regulates calcium and phosphate metabolism and is essential for the
maintenance of bone health. Vitamin D supplementation during infancy, in order to
prevent rickets, is universally accepted. Many human cell types carry vitamin D
receptor, this being a drive for conducting studies on the possible association
between vitamin D status and other diseases. Studies have affirmed that a
considerable number of healthy European children may be vitamin D deficient,
especially in high-risk groups (darker pigmented skin, living in areas with
reduced sun exposure and other disorders). However, the definition of deficiency
is unclear due to inter assay differences and due to a lack of consensus as to
what is an "adequate" 25(OH)D level. Therefore, there is no justification for
routine screening for vitamin D deficiency in healthy children. An evaluation of
vitamin D status is justified in children belonging to high-risk groups. All
infants up to 1 year of age should receive an oral supplementation of 400 IU/day
of vitamin D. Beyond this age, seasonal variation of sunlight should be taken
into account when considering a national policy of supplementation or
fortification.
PMID- 28401347
TI - Calculus migration characterization during Ho:YAG laser lithotripsy by high-speed
camera using suspended pendulum method.
AB - Calculus migration is a common problem during ureteroscopic laser lithotripsy
procedure to treat urolithiasis. A conventional experimental method to
characterize calculus migration utilized a hosting container (e.g., a "V" grove
or a test tube). These methods, however, demonstrated large variation and poor
detectability, possibly attributed to the friction between the calculus and the
container on which the calculus was situated. In this study, calculus migration
was investigated using a pendulum model suspended underwater to eliminate the
aforementioned friction. A high-speed camera was used to study the movement of
the calculus which covered zero order (displacement), first order (speed), and
second order (acceleration). A commercialized, pulsed Ho:YAG laser at 2.1 MUm, a
365-MUm core diameter fiber, and a calculus phantom (Plaster of Paris, 10 * 10 *
10 mm3) was utilized to mimic laser lithotripsy procedure. The phantom was hung
on a stainless steel bar and irradiated by the laser at 0.5, 1.0, and 1.5 J
energy per pulse at 10 Hz for 1 s (i.e., 5, 10, and 15 W). Movement of the
phantom was recorded by a high-speed camera with a frame rate of 10,000 FPS. The
video data files are analyzed by MATLAB program by processing each image frame
and obtaining position data of the calculus. With a sample size of 10, the
maximum displacement was 1.25 +/- 0.10, 3.01 +/- 0.52, and 4.37 +/- 0.58 mm for
0.5, 1, and 1.5 J energy per pulse, respectively. Using the same laser power, the
conventional method showed <0.5 mm total displacement. When reducing the phantom
size to 5 * 5 * 5 mm3 (one eighth in volume), the displacement was very
inconsistent. The results suggested that using the pendulum model to eliminate
the friction improved sensitivity and repeatability of the experiment. A detailed
investigation on calculus movement and other causes of experimental variation
will be conducted as a future study.
PMID- 28401346
TI - CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis
patient iPSCs.
AB - Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with
cellular and molecular mechanisms yet to be fully described. Mutations in a
number of genes including SOD1 and FUS are associated with familial ALS. Here we
report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts
of familial ALS patients bearing SOD1 +/A272C and FUS +/G1566A mutations,
respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9
system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived
from SOD1 +/A272C and corrected iPSCs revealed 899 aberrant transcripts. Our work
may shed light on discovery of early biomarkers and pathways dysregulated in ALS,
as well as provide a basis for novel therapeutic strategies to treat ALS.
PMID- 28401349
TI - Erratum to: Occurrence of arbuscular mycorrhizal fungi in saline soils of the
Tabriz Plain of Iran in relation to some physical and chemical properties of
soil.
PMID- 28401348
TI - Ultrapulsed fractional ablative carbon dioxide laser treatment of hypertrophic
burn scars: evaluation of an in-patient controlled, standardized treatment
approach.
AB - In this study, we aimed to quantify the effects of fractional ablative carbon
dioxide laser therapy in the treatment of widespread hypertrophic burn scars.
While many different pilot studies have described the potential of the technology
and expert groups and current guidelines, alike, recommend its use, the level of
evidence for the efficacy of fractional CO2-laser treatment for burn scars is
currently very low. Ten patients (three male, seven female) with hypertrophic
burn scars were treated with a single course of fractional CO2-laser therapy in
an in-patient controlled setup, using a standardized treatment paradigm.
Documentation was based on modern scar scales and questionnaires, like the
Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS),
and Dermatology Life Quality Index (DLQI), as well as state of the art clinical
measurements (PRIMOS, Cutometer). Over the course of 6 months after treatment,
VSS and POSAS scores showed significant improvement in the rating of scar
parameters, as did the quality of life rating according to the DLQI. In the
treated scars, surface relief improved significantly, as S max decreased by 1893
MUm (-36.92%) (p = 0.0273) and S z by 1615 MUm (-36.37%) (p = 0.0488). Scar
firmness in treated scars could be reduced by 30% after one treatment session, as
R 0 improved by 0.0797 mm (+30.38%) (p = 0.0212). Fractional ablative CO2-laser
treatment is a safe and efficacious option for the treatment of hypertrophic burn
scars. While more treatment sessions are required for satisfying results,
significant improvement is already apparent after a single course of treatment.
PMID- 28401350
TI - Peritoneal fluid biomarkers in the detection of colorectal anastomotic leaks: a
systematic review.
AB - PURPOSE: Anastomotic leak (AL) in colorectal surgery leads to significant
morbidity, mortality and poorer oncological outcomes. Diagnosis of AL is
frequently delayed as current methods of detection are not 100% sensitive or
specific. 'Biomarkers', such as cytokines and markers of ischaemia, from the
milieu of the anastomosis may aid early detection. This paper aims to review the
evidence for their role in AL detection, allowing identification of targets for
future research. METHODS: A systematic review was performed using PubMed, MEDLINE
and Cochrane Library databases. Papers concerning detection or prediction of AL
with biomarkers were identified. References within the papers were used to
identify further relevant articles. RESULTS: Research has taken place in small
cohorts with varying definitions of AL. Lactate has consistently been shown to be
elevated in patients with intra-abdominal complications and ALs. pH on post
operative day 3 showed excellent specificity. Despite mixed results, a meta
analysis found that the cytokines tumour necrosis factor-alpha and interleukin-6
were elevated early in AL. Detection of bacteria in drain fluid by RT-PCR has
good specificity but a high rate of false positives. CONCLUSIONS: Peritoneal
cytokines, lactate and pH have the potential to identify AL early. The
consistency of the results for lactate and pH, alongside the fact that they are
easy, quick and inexpensive to test, makes them the most attractive targets.
Studies in larger cohorts with standardized definitions of AL are required to
clarify their usefulness. Emerging biosensor technology may facilitate the
development of small, low-cost and degradable intra-abdominal devices to measure
peritoneal fluid biomarkers.
PMID- 28401351
TI - Quantification of intrahepatic total HBV DNA in liver biopsies of HBV-infected
patients by a modified version of COBAS(r) Ampliprep/COBAS(r)TaqMan HBV test
v2.0.
AB - Intrahepatic total HBV DNA (it-HBV DNA) level might reflect the size of virus
reservoir and correlate with the histological status of the liver. To quantitate
it-HBV DNA in a series of 70 liver biopsies obtained from hepatitis B chronic
patients, a modified version of the COBAS(r)Ampliprep/COBAS(r)TaqMan HBV test
v2.0 was used for this purpose. The linearity and reproducibility of the modified
protocol was tested by quantifying serial dilutions of a full-length HBV
containing plasmid and it-HBV DNA from a reference patient. A good linear trend
between the expected values and those generated by the assay was observed at
different concentrations of both plasmid and reference patient (R 2 = 0.994 and
0.962, respectively). Differences between the values obtained in two independent
runs were <=0.3 log IU for the plasmid and <=0.6 log IU/mg for the reference
patient, showing a high inter-run reproducibility. In the 70 liver biopsies, it
HBV DNA level ranged from 1.4 to 5.4 log IU/mg, with a good linearity and
reproducibility between the values obtained in two runs [R 2 = 0.981; median
(IQR) difference of it-HBV DNA 0.05 (0.02-0.09) IU/mg]. The modified
COBAS(r)Ampliprep/COBAS(r)TaqMan HBV test v2.0 allows an accurate quantitation of
it-HBV DNA. Its determination may have prognostic value and may be a useful tool
for the new therapeutic strategies aimed at eradicating the HBV infection.
PMID- 28401352
TI - Randomized comparison between provisional and routine kissing-balloon technique
after main vessel crossover stenting for coronary bifurcation lesions.
AB - We compared the myocardial ischemic burden of provisional and routine final
kissing-balloon inflation (FKI) with the 1-stent strategy using a second
generation drug-eluting stent for coronary bifurcation lesions (CBL). There are
no established guidelines for side branch (SB) intervention after main vessel
stenting. In total, 113 CBL patients were randomized to receive different SB
intervention strategies: provisional-FKI group (n = 57; FKI only when SB flow was
TIMI <3) and routine-FKI group (n = 56; mandatory FKI with aggressive treatment
until SB-residual stenosis <50%). Dipyridamole-stress myocardial perfusion
scintigraphy with 99mTc was performed after 8 months. The regional summed
difference score (r-SDS) was calculated according to the coronary territory. The
primary endpoint included target vessel ischemia (TVI; r-SDS >= 2) at 8 months,
whereas the clinical primary endpoint was major adverse cardiovascular events
(MACE) at 3 years. The percent (%) myocardial ischemia (100 * SDS/68) was also
calculated. At 8 months, TVI was identified in 11 and 4% in the provisional-FKI
and routine-FKI groups, respectively (p = 0.226). SB-binary restenosis (48 vs.
4%, p < 0.001) and myocardial ischemia at the SB territory (11 vs. 0%, p = 0.030)
were more common in the provisional-FKI group; however, in TVI patients, %
myocardial ischemia (4.12 +/- 1.23% vs. 3.68 +/- 1.04%; p = 0.677) did not
significantly differ. Moderate/severe ischemia (>10% myocardial ischemia) was not
observed in the target vessel in either group. Long-term cumulative MACE were
similar between the groups (9 vs. 14%; p = 0.358). Provisional-FKI according to
TIMI-SB flow grade led to similar and acceptable myocardial ischemia, in
comparison with routine-FKI, which may contribute to the identical long-term
follow-up.
PMID- 28401353
TI - Maternal fetal loss history and increased acute leukemia subtype risk in
subsequent offspring: a systematic review and meta-analysis.
AB - PURPOSE: History of fetal loss including miscarriage and stillbirth has been
inconsistently associated with childhood (0-14 years) leukemia in subsequent
offspring. A quantitative synthesis of the inconclusive literature by leukemia
subtype was therefore conducted. METHODS: Eligible studies (N = 32) were
identified through the screening of over 3500 publications. Random-effects meta
analyses were conducted on the association of miscarriage/stillbirth history with
overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150
cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia.
Sensitivity and subgroup analyses by age and ALL subtype, as well as meta
regression were undertaken. RESULTS: Fetal loss history was associated with
increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04
1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and
for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in
sensitivity analyses. Notably, stillbirth history was significantly linked to ALL
risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL
and AML with previous miscarriage reached marginal significance. The association
of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60).
CONCLUSIONS: In this meta-analysis involving >50,000 children, we found
noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia
type; namely, of stillbirth with ALL and miscarriage history with infant ALL.
Elucidation of plausible underlying mechanisms may provide insight into leukemia
pathogenesis and indicate monitoring interventions prior to and during pregnancy.
PMID- 28401354
TI - Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by
inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster.
AB - Apoptosis is an important phenomenon in multi cellular organisms for maintaining
tissue homeostasis and embryonic development. Defect in apoptosis leads to a
number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22
nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator
of apoptosis alike other cellular pathways. Recently, small molecules have been
identified as a potent inducer of apoptosis. In this study, we have identified
novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a
negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14)
in a well established in vivo model Drosophila melanogaster where the process of
apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR
13 and miR-14 activity at their target sites, which induce an increased caspase
activity, and in turn influence the caspase dependent apoptotic pathway. These
two compounds also increase the mitochondrial reactive oxygen species (ROS) level
to trigger apoptotic cell death.
PMID- 28401355
TI - Correlation between early surgical complications and readmission rate after
ventral hernia repair.
AB - PURPOSE: Postoperative surgical complications arising from ventral hernia repair
have been assessed by a variety of outcome measures. The objective of this study
was to correlate the Clavien Dindo Classification (CDC) graded complications with
the 30-day readmission rate as early outcome measures in ventral hernia repair.
Secondarily, we wanted to investigate whether the risk factors for Clavien Dindo
class >=1 and 30-day readmission were comparable. METHODS: Single-centre
retrospective study including all patients (>=18 years) who underwent ventral
hernia repair between January 1, 2009 and September 1, 2014 at Zealand University
Hospital. Data were obtained from hospital files and the Danish National Patient
Registry. A 100% follow-up was obtained. RESULTS: In total, the study included
700 patients (261 patients with incisional hernia repair and 439 patients with
umbilical or epigastric hernia repair). There was a significant association
between a complication graded by the CDC >=1 and 30-day readmission for both
incisional and umbilical/epigastric hernia repair (p < 0.001). In incisional
hernia, larger hernia size was an independent risk factor for CDC >=1. No
independent risk was found for 30-day readmission. Recurrent (vs. primary) hernia
repair was an independent risk factors for both CDC >=1 and 30-day readmission in
umbilical/epigastric hernia repair. Furthermore, hernia size 2-7 cm (vs. >2 cm)
was a risk factor for CDC >=1 but not for 30-day readmission in
umbilical/epigastric hernia repair. CONCLUSION: Reports on 30-day readmission can
be used as a general outcome measure in ventral hernia repair, however CDC
provides a more precise and detailed registration of postoperative complications.
PMID- 28401356
TI - Development of novel nomograms to predict renal functional outcomes after
laparoscopic adrenalectomy in patients with primary aldosteronism.
AB - PURPOSE: Most patients with primary aldosteronism (PA) show a significant
decrease in kidney function after surgery. Glomerular hyperfiltration peculiar to
PA can mask mild renal failure before surgery. The aim of this retrospective
study was to investigate postoperative renal functional outcomes in PA patients
from different viewpoints and to develop novel nomograms that can predict renal
functional outcomes in PA patients after surgery. METHODS: 130 Japanese PA
patients treated by unilateral laparoscopic adrenalectomy were retrospectively
surveyed. Pre- and postoperative changes of estimated glomerular filtration rates
(eGFRs) and the distribution of eGFR classification were compared. Furthermore,
predictors of the following renal functional outcomes were investigated: (I) the
percentage decrease >25% in eGFR and (II) the presence of new-onset eGFR <45
ml/min/1.73 m2. Finally, two nomograms that predicted postoperative renal
functional outcomes were developed and internally validated. RESULTS: At 6
months, the average decrease in eGFR was 16.7 mL/min/1.73 m2 (corresponding
percent decrease: 19.7%). Upstaging of eGFR classification was observed in 54.6%
of patients. Age, potassium, plasma aldosterone concentration, and initial eGFR
were incorporated into a nomogram predicting a >25% postoperative decrease in
eGFR. Duration of hypertension and initial eGFR were incorporated into a nomogram
predicting new-onset eGFR <45 ml/min/1.73 m2. The value of the area under the
receiver operating characteristics curve for each nomogram was 0.82 and 0.74,
respectively. CONCLUSION: The first nomograms that can predict postoperative
renal outcomes in PA patients were developed. They will help clinicians calculate
the probability of renal dysfunction in PA patients after laparoscopic
adrenalectomy.
PMID- 28401358
TI - mRNA Cancer Vaccines-Messages that Prevail.
AB - During the last decade, mRNA became increasingly recognized as a versatile tool
for the development of new innovative therapeutics. Especially for vaccine
development, mRNA is of outstanding interest and numerous clinical trials have
been initiated. Strikingly, all of these studies have proven that large-scale GMP
production of mRNA is feasible and concordantly report a favorable safety profile
of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process
comprising antigen acquisition, antigen processing and presentation, as well as
immune stimulation. The effectiveness of mRNA vaccines is critically dependent on
making the antigen(s) of interest available to professional antigen-presenting
cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a
major challenge in the mRNA vaccine field. This review summarizes the principles
of mRNA vaccines and highlights the importance of in vivo mRNA delivery and
recent advances in harnessing their therapeutic potential.
PMID- 28401357
TI - Morphological phenotyping and genetic analyses of a new chemical-mutagenized
population of tobacco (Nicotiana tabacum L.).
AB - MAIN CONCLUSION: A novel tobacco mutant library was constructed, screened, and
characterized as a crucial genetic resource for functional genomics and applied
research. A comprehensive mutant library is a fundamental resource for
investigating gene functions, especially after the completion of genome
sequencing. A new tobacco mutant population induced by ethyl methane sulfonate
mutagenesis was developed for functional genomics applications. We isolated 1607
mutant lines and 8610 mutant plants with altered morphological phenotypes from
5513 independent M2 families that consisted of 69,531 M2 plants. The 2196
mutations of abnormal phenotypes in the M2 putative mutants were classified into
four groups with 17 major categories and 51 subcategories. More than 60% of the
abnormal phenotypes observed fell within the five major categories including
plant height, leaf shape, leaf surface, leaf color, and flowering time. The 465
M2 mutants exhibited multiple phenotypes, and 1054 of the 2196 mutations were
pleiotropic. Verification of the phenotypes in advanced generations indicated
that 70.63% of the M3 lines, 84.87% of the M4 lines, and 95.75% of the M5 lines
could transmit original mutant phenotypes of the corresponding M2, M3, and M4
mutant plants. Along with the increased generation of mutants, the ratios of
lines inheriting OMPs increased and lines with emerging novel mutant phenotypes
decreased. Genetic analyses of 18 stably heritable mutants showed that two
mutants were double recessive, five were monogenic recessive, eight presented
monogenic dominant inheritance, and three presented semi-dominant inheritance.
The pleiotropy pattern, saturability evaluation, research prospects of genome,
and phenome of the mutant populations were also discussed. Simultaneously, this
novel mutant library provided a fundamental resource for investigating gene
functions in tobacco.
PMID- 28401359
TI - Ultrastructure of fat body cells and Malpighian tubule cells in overwintering
Scoliopteryx libatrix (Noctuoidea).
AB - The herald moths, Scoliopteryx libatrix, overwinter in hypogean habitats. The
ultrastructure of their fat body (FB) cells and Malpighian tubule (MT) epithelial
cells was studied by light microscopy and transmission electron microscopy, and
essential biometric and biochemical measurements were performed. The FB was
composed of adipocytes and sparse urocytes. The ultrastructure of both cells did
not change considerably during this natural starvation period, except for rough
endoplasmic reticulum (rER) which became more abundant in March females. In the
cells, the reserve material consisted of numerous lipid droplets, glycogen
rosettes, and protein granula. During overwintering, the lipid droplets
diminished, and protein granula became laminated. The MTs consisted of a
monolayer epithelium and individual muscle cells. The epithelial cells were
attached to the basal lamina by numerous hemidesmosomes. The apical plasma
membrane was differentiated into numerous microvilli, many of them containing
mitochondria. Nuclei were surrounded by an abundant rER. There were numerous
spherites in the perinuclear part of the cells. The basal plasma membrane formed
infoldings with mitochondria in between. Nuclei were located either in the basal
or in the central part of the cells. During overwintering, spherites were
gradually exploited, and autophagic structures appeared: autophagosomes,
autolysosomes, and residual bodies. There were no statistical differences between
the sexes in any measured biometric and biochemical variables in the same time
frames. The energy-supplying lipids and glycogen, and spherite stores were
gradually spent during overwintering. In March, the augmented rER signified the
intensification of synthetic processes prior to the epigean ecophase.
PMID- 28401360
TI - The effects of multiphasic prepulses on automatic and attention-modulated
prepulse inhibition.
AB - Prepulse inhibition (PPI) is widely viewed as an operational measure of
sensorimotor gating. Previous research has shown that sensorimotor gating can
occur automatically and also can be influenced by selective attention. The
present research investigated the relationship of the transient detection
response (TDR) with automatic and attention-modulated PPI using a novel
"multiphasic" prepulse stimulus. Experiment 1 compared discrete versus
multiphasic prepulse types in a no-task PPI protocol to validate multiphasic
prepulses as effective elicitors of automatic sensorimotor gating. Results
revealed that the two prepulse types elicited equivalent levels of PPI.
Experiment 2 compared the effectiveness of continuous monophasic versus
continuous multiphasic prepulses within a task-based PPI protocol using a lead
interval of 120 ms. Results revealed a significant attention effect for
monophasic prepulses only. However, robust PPI was produced by the multiphasic
prepulses independent of attention as well as over time. These results suggest
that multiple influences on PPI can be assessed concurrently depending on
prepulse parameters designed to activate the TDR when used in a PPI protocol
capable of assessing the effects of selective attention on prepulse processing
[corrected]
PMID- 28401361
TI - Erratum to: Empathy, Einfuhlung, and aesthetic experience: the effect of emotion
contagion on appreciation of representational and abstract art using fEMG and
SCR.
PMID- 28401362
TI - Carpal scaphoid non-union treatment: a retrospective trial comparing simple
retrograde percutaneous screw fixation versus percutaneous screw fixation plus
pulsed electromagnetic fields (Physiostim(r)).
AB - BACKGROUND: The purpose of this retrospective comparative study was to assess
whether a complementary treatment by pulsed electromagnetic field could increase
the bone-healing rate of scaphoid non-union without SNAC (scaphoid non-union
advanced collapse) treated by retrograde percutaneous screw fixation. CASE
DESCRIPTION: Eighteen patients with scaphoid non-union were included in this
retrospective study. The group 1 was made of nine cases (seven stage IIA and two
stage IIB) of scaphoid non-union treated by retrograde percutaneous screw
fixation and pulsed electromagnetic fields (Physiostim(r)). The group 2 was made
of nine cases (six stage IIA and three stage IIB) treated by simple retrograde
percutaneous screw fixation. RESULTS: With a 10-month follow-up in group 1 and a
9.5-month follow-up in group 2, there were three cases of non-union in group 1
and two cases in group 2. Regarding the type of non-union, there was one case
among the stage IIB and four cases among the stage IIA. CLINICAL RELEVANCE: The
results of the study did not show any interest in the use of pulsed
electromagnetic field for the treatment of carpal scaphoid non-union. They should
be dropped. LEVEL OF EVIDENCE: III.
PMID- 28401363
TI - Characterization of Marinovum faecis sp. nov., an alphaproteobacterium isolated
from marine sediment.
AB - A Gram-negative, strictly aerobic, chemoheterotrophic, beige-pigmented, ovoid
bacterium, designated YP194T, was isolated from marine sediment in the Republic
of Korea. A phylogenetic analysis based on the 16S rRNA gene sequence indicated
that the novel marine strain belongs to the family Rhodobacteraceae of the class
Alphaproteobacteria, with high sequence similarity (98.4%) to Marinovum algicola
FF3T. The DNA-DNA relatedness values between strains YP194T and M. algicola FF3T
were 34.1 +/- 2.7%. The DNA G+C content of strain YP194T was 63.1 mol%.
Ubiquinone 10 (Q-10) was the sole respiratory quinone. The predominant cellular
fatty acid was C18:1 omega7c (77.6%). Strain YP194T produced
phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an
unidentified aminolipid, an unidentified phospholipid and two unidentified lipids
as polar lipids. From the combination of genotypic and phenotypic characteristics
and the distinct phylogenetic position, the strain is considered to represent a
novel species of the genus Marinovum for which the name Marinovum faecis sp. nov.
is proposed. The type strain of M. faecis sp. nov. is YP194T (= KCCM 90263T =
NBRC 111905T).
PMID- 28401364
TI - Ablative Therapies in Metastatic Breast Cancer: A Systematic Review.
AB - PURPOSE: Patients with oligometastatic breast cancer are being increasingly
offered ablative therapies, yet it is unclear which subpopulations may derive
long-term benefit. This study sought to explore factors that could define a
clinically relevant oligometastatic breast cancer population that benefits from
ablative therapies. METHODS: A systematic review using MEDLINE for English
language articles published between 1985 and April 2014 was undertaken. Criteria
for review included studies that reported overall survival (OS) or progression
free survival (PFS) in breast cancer patients with distant metastases which also:
quantified the extent of disease, had metachronous presentation of metastases,
and reported on at least 5 patients. RESULTS: Of 59 674 screened studies, 41
studies of 1813 individual patients were identified. All studies were
observational cohort studies (level 2B or 4 evidence) and underwent critical
review. All outcomes pertaining to OS and PFS were extracted. Extracted data were
too heterogeneous to facilitate a meta-analysis. The only factor that suggested
worse outcomes was positive margins post-metastasectomy. There was no clear
signal for improved outcomes in regards to age, disease extent, disease-free
interval, or receptor status. CONCLUSION: Existing evidence does not provide
meaningful direction on which metastatic breast cancer patients should have
ablation of their residual disease due to heterogeneous reporting of disease
factors, patient factors, and outcomes. Thorough demonstration of the absence of
high- or moderate-level evidence and the absence of clinical data to guide
patient selection suggests that metastatic breast cancer patients being treated
with ablative modalities should be placed on clinical trial.
PMID- 28401365
TI - Discerning the clinical relevance of biomarkers in early stage breast cancer.
AB - PURPOSE: Prior data suggest that breast cancer patients accept significant
toxicity for small benefit. It is unclear whether personalized estimations of
risk or benefit likelihood that could be provided by biomarkers alter treatment
decisions in the curative setting. METHODS: A choice-based conjoint (CBC) survey
was conducted in 417 HER2-negative breast cancer patients who received
chemotherapy in the curative setting. The survey presented pairs of treatment
choices derived from common taxane- and anthracycline-based regimens, varying in
degree of benefit by risk of recurrence and in toxicity profile, including
peripheral neuropathy (PN) and congestive heart failure (CHF). Hypothetical
biomarkers shifting benefit and toxicity risk were modeled to determine whether
this knowledge alters choice. Previously identified biomarkers were evaluated
using this model. RESULTS: Based on CBC analysis, a non-anthracycline regimen was
the most preferred. Patients with prior PN had a similar preference for a taxane
regimen as those who were PN naive, but more dramatically shifted preference away
from taxanes when PN was described as severe/irreversible. When modeled after
hypothetical biomarkers, as the likelihood of PN increased, the preference for
taxane-containing regimens decreased; similarly, as the likelihood of CHF
increased, the preference for anthracycline regimens decreased. When evaluating
validated biomarkers for PN and CHF, this knowledge did alter regimen preference.
CONCLUSIONS: Patients faced with multi-faceted decisions consider personal
experience and perceived risk of recurrent disease. Biomarkers providing
information on likelihood of toxicity risk do influence treatment choices, and
patients may accept reduced benefit when faced with higher risk of toxicity in
the curative setting.
PMID- 28401366
TI - Resistance to immunotherapy: clouds in a bright sky.
AB - Two major challenges persist for an optimal management of immunotherapy: i)
identifying those patients who will benefit from this type of therapy, and ii)
determining the biological, cellular and molecular mechanisms that trigger
disease progression while on therapy. There is a consensual view in favor of
standardizing practices currently used to measure programmed death ligand 1 (PD
L1) expression that relates to innate resistance. The tumor mutation landscape
has been widely explored as a potential predictor of treatment efficacy. In
contrast, our knowledge is rather limited as concerns the mechanisms sustaining
acquired resistance to checkpoint blockade immunotherapy in patients under
treatment. Upregulation of T cell immunoglobulin mucin domain 3 (TIM-3) in CD8+ T
cells has been reported in patients developing acquired resistance to anti-PD-1
treatment. Resistance mechanisms are even more complex for combinatorial
strategies linking immunotherapeutic agents and conventional therapies, an area
that is expanding rapidly. However, with the arrival of advanced analytical
methods such as mass cytometry, there is reason for optimism. These methods can
identify cellular mechanisms governing response to therapy and resistance. The
clinical use of inhibitors of tumor-microenvironment-modulated pathways, such as
those targeting indoleamine 2, 3-dioxygenase (IDO), hold promise for resistance
management. Graphical abstract Clouds in a bright sky - Joseph Mallord William
Turner.
PMID- 28401368
TI - Erratum to: MiR-9-5p Down-Regulates PiT2, but not PiT1 in Human Embryonic Kidney
293 Cells.
PMID- 28401367
TI - Perfluoroalkyl acids (PFAAs) in sediments from rivers of the Pearl River Delta,
southern China.
AB - Having been largely used in industrial and household products, perfluoroalkyl
acids (PFAAs) appear in environmental and biological systems with prevalence and
persistence and have raised great concern in recent years. The present study is
aimed at studying concentrations and composition profiles of 16 PFAAs in surface
sediments collected from 51 sampling locations in 4 main rivers of the Pearl
River Delta, one of the economy-developed areas in China. The total PFAA
concentrations (? PFAAs) were determined in a wide range of 1.89-15.1 ng g-1 dw
(dry weight) with an average concentration to be 3.54 ng g-1 dw. Higher ? PFAAs
were observed in the downstream of Dongjiang River and the Pearl River, possibly
due to the discharge of industrial wastewater. Perfluoropentanoic acid (PFPeA)
and perfluorooctane sulfonate (PFOS) were the dominant PFAAs, accounting for 51
to 85% of ? PFAAs in 27% of the samples. High PFPeA concentrations in sediments
of urban river were scarcely observed in previous studies worldwide. The sources
of short-chain perfluoroalkyl carboxylic acids (PFCAs) were significantly
different from those of other PFAAs. Preliminary hazard assessment proved
negligible for PFOS, perfluorooctanoic acid (PFOA), PFPeA, and perfluorohexanoic
acid (PFHxA) concentrations in sediments from rivers of the Pearl River Delta.
PMID- 28401369
TI - The Importance of VEGF-KDR Signaling Pathway Genes should Not Be Ignored When the
Risk of Developing Multiple Sclerosis is Taken into Consideration.
AB - Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain
containing receptor (KDR) pathway trigger the process of angiogenesis as well as
inflammation, which contributes to the development and progression of
demyelinating lesions in multiple sclerosis. This work is a case-control study
comprising of a total of 400 subjects with multiple sclerosis and 400 healthy
controls. Participants were subjected to neurological examination and peripheral
blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were
assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A
significantly higher frequency of the T allele and TT genotype of the VEGF 936C >
T (rs3025039) polymorphism was found in the multiple sclerosis group than in the
healthy control group (P = 0.01 [OR = 1.41] and P = 0.01 [OR = 3.12],
respectively). In addition, VEGF 936C > T showed an association with patients
in a recessive model. However, the KDR -604T > C (rs2071559) polymorphism showed
no significant difference in either allelic or genotype frequency between the two
groups. Taken together, the results of the present study suggests that the T
allele of the rs3025039 in VEGF gene could be considered a risk factor for
developing multiple sclerosis in the Iranian population.
PMID- 28401370
TI - The Research on the Relationship of RAGE, LRP-1, and Abeta Accumulation in the
Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats.
AB - Diabetes mellitus (DM) has been regarded as an important risk factor for
Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive
dysfunction. More research has shown that the amyloid-beta (Abeta), which is a
hallmark of AD, was found deposited in the hippocampus of diabetic rats. This
Abeta accumulation is regulated by the receptor for advanced glycation end
products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1).
However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In
the present study, we used streptozotocin (STZ)-induced diabetic rats to
investigate whether the expression of RAGE and LRP-1 is related to Abeta1-42
deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that
diabetic rats had longer escape latency and less frequency of entrance into the
target zone than that of the control group (P < 0.05) in the Morris water maze
(MWM) test. The Abeta1-42 expression in the hippocampus and prefrontal lobe
significantly increased in the DM group compared to the control group (P < 0.05).
RAGE increased (P < 0.05), while LRP-1 decreased (P < 0.05) in the hippocampus
tissue and prefrontal lobe tissue of DM rats. The Abeta1-42 deposition was
correlated with RAGE positively (P < 0.05), but with LRP-1 negatively (P < 0.05).
Further, the expression levels of Abeta1-42, RAGE, and LRP-1 were not changed in
the amygdala between the diabetic rats and the control group. These findings
indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus
and the prefrontal lobe contributed to the Abeta1-42 accumulation and then
further promoted the cognitive impairment of diabetic rats.
PMID- 28401371
TI - Glutamate Toxicity to Differentiated Neuroblastoma N2a Cells Is Prevented by the
Sesquiterpene Lactone Achillolide A and the Flavonoid 3,5,4'-Trihydroxy-6,7,3'
Trimethoxyflavone from Achillea fragrantissima.
AB - Glutamate toxicity is a major contributor to the pathophysiology of numerous
neurodegenerative diseases including amyotrophic lateral sclerosis and
Alzheimer's disease. Therefore, protecting neuronal cells against glutamate
induced cytotoxicity might be an effective approach for the treatment of these
diseases. We have previously purified from the medicinal plant Achillea
fragrantissima two bioactive compounds which were not studied before: the
sesquiterpene lactone achillolide A and the flavonoid 3,5,4'-trihydroxy-6,7,3'
trimethoxyflavone (TTF). We have shown that these compounds protect astrocytes
from oxidative stress-induced cell death and inhibit microglial activation. The
current study examined for the first time their effects on differentiated mouse
neuroblastoma N2a cells and on glutamate toxicity. We have found that, although
these compounds belong to different chemical families, they protect neuronal
cells from glutamate toxicity. We further demonstrate that this protective effect
might be, at least partially, due to inhibitory effects of these compounds on the
levels of reactive oxygen species produced following treatment with glutamate.
PMID- 28401372
TI - Choroidal thickness alterations in diabetic nephropathy patients with early or no
diabetic retinopathy.
AB - PURPOSE: To assess changes in choroidal thickness (CT) in diabetes patients with
and without diabetic nephropathy using enhanced depth imaging spectral domain
optical coherence tomography (EDI-OCT). METHODS: Thirty-five type 2 diabetes
patients with a diagnosis of diabetic nephropathy (DNP) in nephrology department
and 35 type 2 diabetes patients without nephropathy (non-DNP) were included in
our prospective study consecutively. The control group comprised 34 healthy
individuals. CT measurements were recorded under the fovea and at 1500 um from
the foveal center in the nasal and temporal sides. The study parameters also
included age, refractive error, axial length, intraocular pressure, HbA1c,
glomerular filtration rate and proteinuria amount. RESULTS: The subfoveal,
temporal and nasal choroidal thickness was noted to be thinner in patients with
DNP compared with non-DNP and normal subjects (p < 0.05). However, CT
measurements did not show any difference between the healthy and non-DNP group.
CONCLUSION: CT decreases significantly in diabetic patients when diabetic
nephropathy accompanies diabetes mellitus.
PMID- 28401374
TI - Does early resection of presumed low-grade glioma improve survival? A clinical
perspective.
AB - Early resection is standard of care for presumed low-grade gliomas. This is based
on studies including only tumors that were post-surgically confirmed as low-grade
glioma. Unfortunately this does not represent the clinicians' situation wherein
he/she has to deal with a lesion on MRI that is suspect for low-grade glioma
(i.e. without prior knowledge on the histological diagnosis). We therefore aimed
to determine the optimal initial strategy for patients with a lesion suspect for
low-grade glioma, but not histologically proven yet. We retrospectively
identified 150 patients with a resectable presumed low-grade-glioma and who were
otherwise in good clinical condition. In this cohort we compared overall survival
between three types of initital treatment strategy: a wait-and-scan approach (n =
38), early resection (n = 83), or biopsy for histopathological verification (n =
29). In multivariate analysis, no difference was observed in overall survival for
early resection compared to wait-and-scan: hazard ratio of 0.92 (95% CI 0.43
2.01; p = 0.85). However, biopsy strategy showed a shorter overall survival
compared to wait-and-scan: hazard ratio of 2.69 (95% CI 1.19-6.06; p = 0.02). In
this cohort we failed to confirm superiority of early resection over a wait-and
scan approach in terms of overall survival, though longer follow-up is required
for final conclusion. Biopsy was associated with shorter overall survival.
PMID- 28401375
TI - Trace elements in surface sediments of the Hooghly (Ganges) estuary: distribution
and contamination risk assessment.
AB - Our objective was to evaluate distribution and accumulation of trace elements
(TEs) in surface sediments along the Hooghly (Ganges) River Estuary, India, and
to assess the potential risk with view to human health. The TE concentrations (mg
kg-1 dry weight) exhibited a wide range in the following order: Al (31.801 +/-
15.943) > Fe (23.337 +/- 7584) > Mn (461 +/- 147) > S (381 +/- 235) > Zn (54 +/-
18) > V (43 +/- 14) > Cr (39 +/- 15) > As (34 +/- 15) > Cu (27 +/- 11) > Ni (24
+/- 9) > Se (17 +/- 8) > Co (11 +/- 3) > Mo (10 +/- 2) > Hg (0.02 +/- 0.01).
Clay, silt, iron, manganese and sulphur were important for the accumulation of TE
in the sediments as confirmed by factor analysis and Pearson correlation. The
accumulation and dispersal of TEs were most likely to be governed by both tide
induced processes and anthropogenic inputs from point and non-point sources.
Enrichment factor analysis and geoaccumulation index revealed serious
contamination of the sediments with Se and As, while comparing the consensus
based sediment quality guidelines (SQGs), adverse biological effects to benthic
fauna might be caused by As, Cu, Ni and Cr. This investigation may serve as a
model study and recommends continuous monitoring of As, Se, Cu, Ni and Cr to
ascertain that SQGs with respect to acceptable levels of TEs to safeguard
geochemical health and ecology in the vicinity of this estuary.
PMID- 28401376
TI - Selenium deficiency in subtropical littoral pampas: environmental and dietary
aspects.
AB - Se deficiency has a critical effect on human health. The littoral near Patos
Lagoon in the south of Brazil is composed of Quaternary sandy deposits and
nutrient-deficient soils, which contribute to Se deficiency in the surrounding
environment. The average concentration of Se in littoral soils is six times lower
than the metalloid deficiency threshold of 0.5 mg kg-1 and is close to that in
countries where Keshan disease is registered. The sediments in the Patos Estuary
are also notably lower in Se than near-shore marine sediments. Foodstuffs
produced in the littoral pampas are characterised by extremely low Se
concentrations compared with the same alimentary products reported worldwide. The
total daily dietary intake of Se in the region is 24 MUg day-1, which is half the
Estimated Average Requirement for adults. Black beans in the local diet provide
over 40% of daily Se intake. Prescriptive addition of Se to prevalent products
seems the most effective solution to the problem of metalloid dietary deficiency
in the region. Similar environmental conditions and significant concentration of
the population in the littoral zone suggest that the problem of Se deficiency
probably affects a large proportion of the population along the Atlantic coast of
Brazil.
PMID- 28401373
TI - Sulfated glycosaminoglycans in protein aggregation diseases.
AB - Protein aggregation diseases are characterized by intracellular or extracellular
deposition of misfolded and aggregated proteins. These aggregated deposits
contain multiple proteinaceous and non-protein components that are thought to
play critical roles in the etiology and pathogenesis of protein aggregation
diseases in vivo. One of these components, the sulfated glycosaminoglycans
(GAGs), includes heparan sulfate, chondroitin sulfate, and keratan sulfate. The
sulfated GAGs are negatively charged heteropolysaccharides expressed in all
mammalian tissues. Enzymatically generated structural patterns and the degree of
sulfation in GAGs determine GAGs' specific interactions with their protein
ligands. Here, we review the potential roles of the sulfated GAGs in the
pathogenesis and progression of protein aggregation diseases from a perspective
of their sulfation modification. We also discuss the possibility of sulfated GAGs
as therapeutic targets for protein aggregation diseases.
PMID- 28401377
TI - A Mathematical Model of Forager Loss in Honeybee Colonies Infested with Varroa
destructor and the Acute Bee Paralysis Virus.
AB - We incorporate a mathematical model of Varroa destructor and the Acute Bee
Paralysis Virus with an existing model for a honeybee colony, in which the bee
population is divided into hive bees and forager bees based on tasks performed in
the colony. The model is a system of five ordinary differential equations with
dependent variables: uninfected hive bees, uninfected forager bees, infected hive
bees, virus-free mites and virus-carrying mites. The interplay between forager
loss and disease infestation is studied. We study the stability of the disease
free equilibrium of the bee-mite-virus model and observe that the disease cannot
be fought off in the absence of varroacide treatment. However, the disease-free
equilibrium can be stable if the treatment is strong enough and also if the virus
carrying mites become virus-free at a rate faster than the mite birth rate. The
critical forager loss due to homing failure, above which the colony fails, is
calculated using simulation experiments for disease-free, treated and untreated
mite-infested, and treated virus-infested colonies. A virus-infested colony
without varroacide treatment fails regardless of the forager mortality rate.
PMID- 28401378
TI - Protective Effect of Juglans regia L. Walnut Extract Against Oxidative DNA
Damage.
AB - Walnuts (Juglans regia L.) are relevant components of the Mediterranean diet
providing important macronutrients, micronutrients and other bioactive
constituents including unsaturated fatty acids, proteins, fiber, vitamins,
minerals, phytosterols and polyphenols. Although the walnut beneficial effects in
human health are widely recognized by a lot of epidemiologic studies very little
is known regarding its effect on damaged DNA. The aim of the present study was to
investigate the effect of Juglans regia L. ethanolic extract from kernel on the
induction of DNA strand breaks by thiol/Fe3+/O2 mixed function oxidase, tert
butyl hydroperoxide or UVC radiations in acellular and cellular models. Plasmid
DNA cleavage and fast Halo assay were used to monitor oxidative damage to DNA.
Both approaches showed protection of oxidatively injured DNA. These results agree
with a lot of scientific proofs which recommend walnut as dietary adjunct in
health promotion and prevention as well as in treatment of lifestyle-related
oxidative diseases.
PMID- 28401379
TI - Kidney-lung pathophysiological crosstalk: its characteristics and importance.
AB - Crosstalk between the lung and the kidney is based on the similarities that these
organs share. This is why different diseases that affect one organ can have
repercussions on the other. Patients with acute kidney injury can present
complications such as pulmonary edema and require mechanical ventilation in
respiratory failure. This interaction occurs due to the increase in systemic
immune mediators that cause inflammatory reactions, oxidative stress, and an
increase in vascular permeability in the lung. With regard to lung-induced renal
damage, the kidney can also be affected by chemical mediators, which are
translocated into the bloodstream. Moreover, the kidneys are extremely sensitive
to oxygen changes which can cause them to lose their autoregulation mechanism. In
patients with acute lung injury (ALI), oxygen supply is decreased causing renal
hypoxia. Besides, hypercapnia generated by ALI causes vasoconstriction in the
renal vascular network and activation of the renal angiotensin aldosterone
system. ALI not only can cause renal injury, but also worsening chronic
obstructive pulmonary disease and obstructive sleep apnea. In conclusion, kidney
lung crosstalk is commonly present in certain pathological states, and knowing
its characteristics is crucial for managing the complications which may arise
from this vicious circle.
PMID- 28401380
TI - Fate of newly developed pulmonary embolism after surgery for renal cell carcinoma
with vena cava thrombus.
AB - PURPOSE: Pulmonary embolism with viable tumor cells developed after surgery for
renal cell carcinoma may metastasize to lung. We investigated the incidence and
fate of newly developed pulmonary embolism after surgery for renal cell carcinoma
with vena cava thrombus. METHODS: Among 4549 renal cell carcinoma patients
treated with curative surgery at our institute from 1998 to 2015, 81 non
metastatic renal cell carcinoma patients with vena cava thrombus were included.
The clinical course of pulmonary embolism and its impact on oncological outcomes
were assessed. RESULTS: Postoperatively, pulmonary embolism developed in 13
patients (16.0%), who had higher level of vena cava thrombus (p = 0.004), more
frequent liver mobilization (p = 0.005), and higher amount of intraoperative
transfusion (p = 0.024) than patients without pulmonary embolism. The rate of
lung metastasis was similar between patients with and without pulmonary embolism
(30.8 vs. 35.3%, p = 1.000). In the multivariate analysis, the significant risk
factors for disease recurrence were non-clear cell histology (p = 0.014) and
larger primary renal tumor size (p = 0.032). Non-clear cell histology (p = 0.003)
was the only significant risk factor for cancer-specific survival. Pulmonary
embolism was not associated with both recurrence-free and cancer-specific
survival. CONCLUSIONS: Pulmonary embolism after surgery for renal cell carcinoma
with vena cava thrombus was not associated with worse oncological outcomes and
can be closely followed up with anticoagulation therapy.
PMID- 28401381
TI - Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer.
AB - Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors
is the current first-line treatment in metastatic renal cell carcinoma (mRCC).
Immunotherapy with checkpoint inhibitor has been recently added to the
armamentarium of mRCC treatment. These therapies are based on treatment with
antibodies that block programmed cell death-1 (PD-1), programmed cell death
ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved
survival in several tumour types. So far, nivolumab is the only approved anti-PD
1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and
clinical studies, combination therapies with VEGF- and checkpoint inhibitors have
synergistic effect achieving improved response rates. However, toxicity in some
combinations is high. In this article, we present a review of the ongoing trials
with these drug combinations for RCC.
PMID- 28401382
TI - First Application of Newly Developed FT-NIR Spectroscopic Methodology to Predict
Authenticity of Extra Virgin Olive Oil Retail Products in the USA.
AB - Economically motivated adulteration (EMA) of extra virgin olive oils (EVOO) has
been a worldwide problem and a concern for government regulators for a long time.
The US Food and Drug Administration (FDA) is mandated to protect the US public
against intentional adulteration of foods and has jurisdiction over deceptive
label declarations. To detect EMA of olive oil and address food safety
vulnerabilities, we used a previously developed rapid screening methodology to
authenticate EVOO. For the first time, a recently developed FT-NIR spectroscopic
methodology in conjunction with partial least squares analysis was applied to
commercial products labeled EVOO purchased in College Park, MD, USA to rapidly
predict whether they are authentic, potentially mixed with refined olive oil (RO)
or other vegetable oil(s), or are of lower quality. Of the 88 commercial products
labeled EVOO that were assessed according to published specified ranges, 33
(37.5%) satisfied the three published FT-NIR requirements identified for
authentic EVOO products which included the purity test. This test was based on
limits established for the contents of three potential adulterants, oils high in
linoleic acid (OH-LNA), oils high in oleic acid (OH-OLA), palm olein (PO), and/or
RO. The remaining 55 samples (62.5%) did not meet one or more of the criteria
established for authentic EVOO. The breakdown of the 55 products was EVOO
potentially mixed with OH-LNA (25.5%), OH-OLA (10.9%), PO (5.4%), RO (25.5%), or
a combination of any of these four (32.7%). If assessments had been based
strictly on whether the fatty acid composition was within the established ranges
set by the International Olive Council (IOC), less than 10% would have been
identified as non-EVOO. These findings are significant not only because they were
consistent with previously published data based on the results of two sensory
panels that were accredited by IOC but more importantly each measurement/analysis
was accomplished in less than 5 min.
PMID- 28401383
TI - Gallstone Disease After Laparoscopic Sleeve Gastrectomy in an Asian Population
What Proportion of Gallstones Actually Becomes Symptomatic?
AB - BACKGROUND: Despite evidence on gallstone disease after laparoscopic sleeve
gastrectomy (LSG), there is an existing lack of consensus on practice guidelines,
i.e., surveillance and stone-lowering prophylaxis. Available evidence also has a
racial bias as western reports predominate current data. Considering the growing
popularity of LSG in Asia and the unique Asian anthropometrics, we have attempted
to provide a regional perspective by reviewing our LSG database to investigate
the epidemiology of this complication. METHODS: One hundred two morbidly obese
cases were retrospectively reviewed. Abdominal ultrasounds were conducted
preoperatively and at 12-month post-op. No gallstone-lowering prophylaxis was
used. Outcome measure was the incidence of new gallstone formation at 1 year and
the rate of symptomatic stones during the follow-up period. RESULTS: Mean age was
43 years (range 20-68) with average initial BMI of 41.68 kg/m2. Preoperative
gallstones were present in 14 (13.7%) cases. At 12-month post-op, 24 (27.5%)
patients with no previous gallstone disease developed new stones. Within the mean
follow-up period of 28.4 months, only one case (0.9%) developed gallstone
complication requiring a cholecystectomy. We found no statistical difference in
demographics, BMI variables (initial BMI, DeltaBMI at 6 months and 1 year), and
comorbidities between patients with new gallstone and those without stones.
CONCLUSION: Our results match western data in that gallstone formation is common
after LSG though incidence of complicated stones is small. This is despite not
using gallstone-lowering prophylaxis. The low conversion rate also questions the
relevance of surveillance screening, as most patients with new gallstones remain
asymptomatic at least in the short-term follow-up.
PMID- 28401384
TI - Bone Involvement in Rosai-Dorfman Disease (RDD): a Case Report and Systematic
Literature Review.
AB - PURPOSE OF REVIEW: Rosai-Dorfman disease (RDD) is a rare histiocytic disorder
typically presenting as painless cervical lymphadenopathy. Extranodal involvement
is common and may also affect bones. Here, we present a patient with typical
nodal disease and multifocal bone manifestations. Further, a systematic
literature review was performed to better understand the phenotype, clinical
course and treatment options of such patients. RECENT FINDINGS: RDD is a
nonmalignant, classically sporadic histiocytosis. Nevertheless, increasing
evidence also suggests familial forms of the disease. According to our literature
review, bone involvement is exceedingly rare and heterogeneous. Clinical outcome
in terms of mortality seems to be favorable in most cases. Currently, therapy
strategies include surgical and immunosuppressive treatments, but the optimal
treatment of osseous RDD remains to be defined. Patients with osseous RDD may
present to rheumatologists with arthralgia or arthritis. Due to the rarity of the
disease, diagnosis and treatment remain challenging.
PMID- 28401385
TI - Enrofloxacin degradation in broiler chicken manure under field conditions and its
residuals effects to the environment.
AB - The rate of degradation of enrofloxacin in broiler chicken manure has been
characterised. Its degradation was investigated in manure excreted by broiler
chickens in an intensively reared chicken facility; further, the degradation also
followed after transfer of the excreta into the natural environment occurred. The
effect of enrofloxacin and its degradation products on cucumber and tomato was
also investigated. Enrofloxacin degradation was shown to take place within the
rearing facility and also continuing after the manure was transferred into the
environment. The rates of enrofloxacin degradation and the degree of degradation
product formation in the manure heap incubated in the environment were condition
specific, both variables depending on the manure sampling depth. The degradation
half-lives ranged from 12.7 to 38.1 days for enrofloxacin and from 1.2 to 8.2
days for the main metabolite ciprofloxacin. Only the cucumber showed signs of
toxicity when incubated with the composted manure immediately after transfer into
field occurred (t = 0). No toxic effects to plants were observed when manure from
the last incubation day (60th) of the field study and manure from the last
incubation day of the laboratory degradation study were applied. The degradation
study under field conditions showed that enrofloxacin and its degradation
products degrade fast in the environment. Additionally, the toxic effects to
plants decrease with the incubation time of manure containing enrofloxacin
residuals.
PMID- 28401386
TI - A comprehensive review on removal of arsenic using activated carbon prepared from
easily available waste materials.
AB - Arsenic contamination in water bodies is a serious problem and causes various
health problems due to which US Environment Protection Agency (USEPA) set its
maximum permissible limit of 10 ppb. The present review article starts with the
removal of toxic arsenic using adsorbents prepared from easily available waste
materials. Adsorbent either commercial or low-cost adsorbent can be used for
arsenic removal but recent research was focused on the low-cost adsorbent.
Preparation and activation of various adsorbents were discussed. Adsorption
capacities, surface area, thermodynamic, and kinetics data of various adsorbents
for As(III) and As(V) removal were compiled. Desorption followed by regeneration
and reuse of adsorbents is an important step in adsorption and leads to
economical process. Various desorbing and regenerating agents were discussed for
arsenic decontamination from the adsorbent surface. Strong acids, bases, and
salts are the main desorbing agents. Disposal of arsenic-contaminated adsorbent
and arsenic waste was also a big problem because of the toxic and leaching effect
of arsenic. So, arsenic waste was disposed of by proper
stabilization/solidification (S/S) technique by mixing it in Portland cement,
iron, ash, etc. to reduce the leaching effect.
PMID- 28401387
TI - Quantifying microplastic pollution on sandy beaches: the conundrum of large
sample variability and spatial heterogeneity.
AB - Despite the environmental risks posed by microplastic pollution, there are
presently few standardized protocols for monitoring these materials within marine
and coastal habitats. We provide a robust comparison of methods for sampling
microplastics on sandy beaches using pellets as a model and attempt to define a
framework for reliable standing stock estimation. We performed multiple
comparisons to determine: (1) the optimal size of sampling equipment, (2) the
depth to which samples should be obtained, (3) the optimal sample resolution for
cross-shore transects, and (4) the number of transects required to yield
reproducible along-shore estimates across the entire sections of a beach. Results
affirmed that the use of a manual auger with a 20-cm diameter yielded the best
compromise between reproducibility (i.e., standard deviation) and
sampling/processing time. Secondly, we suggest that sediments should be profiled
to a depth of at least 1 m to fully assess the depth distribution of pellets.
Thirdly, although sample resolution did not have major consequence for overall
density estimates, using 7-m intervals provides an optimal balance between
precision (SD) and effort (total sampling time). Finally, and perhaps most
importantly, comparing the minimum detectable difference yielded by different
numbers of transects along a given section of beach suggests that estimating
absolute particle density is probably unviable for most systems and that
monitoring might be better accomplished through hierarchical or time series
sampling efforts. Overall, while our study provides practical information that
can improve sampling efforts, the heterogeneous nature of microplastic pollution
poses a major conundrum to reproducible monitoring and management of this
significant and growing problem.
PMID- 28401388
TI - Accumulation of heavy metal in scalp hair of people exposed in Beijing sewage
discharge channel sewage irrigation area in Tianjin, China.
AB - Heavy metal concentrations in soil, wheat, and scalp hair exposed to Beijing
sewage discharge channel sewage irrigation area (BSIA) in Tianjin were studied to
evaluate the influence of sewage irrigation. Results showed that the continuous
application of wastewater has led to an accumulation of heavy metals in the soil,
with 55.2 and 8.62% of soil samples accumulating Cd and Zn, respectively, at
concentrations exceeding the permissible limits in China. Concentrations of heavy
metals in wheat grain from BSIA were higher than these from the clean water
irrigation area by 63.2% for Cd, 3.8% for Cu, 100% for Pb, 6.6% for Zn, and
326.7% for Cr. The heavy metal bioaccumulation factor (BAF) of wheat/soil in BSIA
showed the following order: Zn > Cd > Cu > Pb > Cr. Interestingly, these
accumulation of heavy metals in soil after sewage irrigation could increase the
migration ability of heavy metals (particularly Zn and Cd) from soil to wheat.
Mean concentrations of heavy metals in the hair of residents followed the
decreasing trend of Zn > Cu > Pb > Cr > Cd, which were higher than the control
area by 110.0% for Cd, 20.0% for Cu, 55.9% for Zn, 36.6% for Pb, and 64.6% for
Cr. Concentrations of heavy metals in male human hair in BSIA were higher than
those of females. And the concentrations of heavy metals except for Pb in human
hair increased with their increasing ages. The heavy metal BAF values of
wheat/soil in BSIA showed the trend of Zn (98.0057) > Pb (7.0162) > Cr (5.5788) >
Cu (5.4853) > Cd (3.5584); heavy metals had obvious biological amplification from
wheat to human hair. These results indicated that local population health was
potentially exposed to the heavy metal risk via wheat consumption.
PMID- 28401389
TI - Spatial variation of PAHs and PCBs in coastal air, seawater, and sediments in a
heavily industrialized region.
AB - Concurrent coastal seawater (n = 22), sediment (n = 22), and atmospheric samples
(n = 10) were collected in the Aliaga industrial region, Turkey, to explore the
spatial variation, sources, and air-seawater exchange of polycyclic aromatic
hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Seawater Sigma16PAH
concentrations (particle + dissolved) ranged between 5107 and 294,624 pg L-1,
while Sigma41PCB concentrations were in the range of 880-50,829 pg L-1. Levels in
sediments were highly variable ranging between 35.5-49,682 and 2.7-2450 MUg kg-1
in dry weight for Sigma16PAHs and Sigma41PCBs, respectively. Atmospheric
concentrations varied between 1791-274,974 and 104-20,083 pg m-3 for Sigma16PAHs
and Sigma41PCBs, respectively. Sediment organic matter (OM) content and levels of
Sigma16PAHs and Sigma41PCBs correlated weakly (r 2 = 0.19-0.23, p < 0.05)
suggesting that the spatial variations of PAHs and PCBs were mainly affected by
local sources rather than their sorption to OM. The geographical distribution of
PAH and PCB concentrations in air, seawater, and sediment and factor analysis on
the sediment levels pointed out that the major sources in the region are steel
plants, petroleum refinery, petrochemical complex, ship breaking,
loading/unloading activities at the ports, vehicular emissions, and fossil fuel
combustion emissions. The direction of the air-seawater exchange was also
explored by estimating seawater fugacity fractions of PAHs and PCBs. For PAHs,
the number of cases implying deposition (43.0%) and volatilization (39.5%) was
similar, while for PCBs, the number of cases implying volatilization (60.4%) was
much higher compared to deposition (21.6%). Fugacity fractions were generally
<0.36 (deposition) at the sites close to industrial and ship breaking activities
where the highest seawater and sediment levels were measured, implying that
atmospheric deposition is an important mechanism affecting seawater and sediment
PAH and PCB levels.
PMID- 28401390
TI - Enzyme-based solutions for textile processing and dye contaminant biodegradation
a review.
AB - The textile industry, as recognized conformist and stake industry in the world's
economy, is facing serious environmental challenges. In numerous industries, in
practice, various chemical-based processes from initial sizing to final washing
are fascinating harsh environment concerns. Some of these chemicals are corrosive
to equipment and cause serious damage itself. Therefore, in the twenty-first
century, chemical and allied industries quest a paradigm transition from
traditional chemical-based concepts to a greener, sustainable, and
environmentally friendlier catalytic alternative, both at the laboratory and
industrial scales. Bio-based catalysis offers numerous benefits in the context of
biotechnological industry and environmental applications. In recent years, bio
based processing has received particular interest among the scientist for inter-
and multi-disciplinary investigations in the areas of natural and engineering
sciences for the application in biotechnology sector at large and textile
industries in particular. Different enzymatic processes such as chemical
substitution have been developed or in the process of development for various
textile wet processes. In this context, the present review article summarizes
current developments and highlights those areas where environment-friendly
enzymatic textile processing might play an increasingly important role in the
textile industry. In the first part of the review, a special focus has been given
to a comparative discussion of the chemical-based "classical/conventional"
treatments and the modern enzyme-based treatment processes. Some relevant
information is also reported to identify the major research gaps to be worked out
in future.
PMID- 28401391
TI - Temporal abundance and activity trends of vinyl chloride (VC)-degrading bacteria
in a dilute VC plume at Naval Air Station Oceana.
AB - Assessment and monitoring of microbial community dynamics is useful when tracking
the progress of vinyl chloride (VC) bioremediation strategies, particularly in
dilute plumes where apparent VC attenuation rates are low. In a long-term field
study, the abundance and the activity of microbial VC degraders were tracked in
three monitoring wells (MW05, MW25, and MW19) along a dilute VC plume at Naval
Air Station (NAS) Oceana. High-throughput sequencing of partial 16S ribosomal RNA
(rRNA) genes and transcripts revealed diverse groundwater microbial communities
and showed that methanotrophs and anaerobic respirers (e.g., methanogens, sulfate
reducers, and iron reducers) were among the most active and abundant guilds.
Quantitative PCR analysis showed that among bacterial guilds with a potential to
contribute to VC biodegradation, methanotrophs were the most abundant and active
microbial group. Ethene-oxidizing bacterial populations were less abundant and
relatively inactive compared to methanotrophs. In MW19, expression of functional
genes associated with both aerobic VC oxidation and anaerobic VC reduction was
observed. Overall, our results reveal that the groundwater community contains
various active bacterial guilds previously associated with metabolic and
cometabolic VC degradation processes either under aerobic and anaerobic
conditions that might have contributed to the slowly decreasing VC concentrations
at the NAS Oceana site over the 6-year study period.
PMID- 28401392
TI - Phytotoxicity of CeO2 nanoparticles on radish plant (Raphanus sativus).
AB - Cerium oxide nanoparticles (CeO2 NPs) have been considered as one type of
emerging contaminants that pose great potential risks to the environment and
human health. The effect of CeO2 NPs on plant-edible parts and health evaluation
remains is necessary and urgently to be developed. In this study, we cultivated
radish in Sigma CeO2 NP (<25 nm)-amended soils across a series of concentration
treatments, i.e., 0 mg/kg as the control and 10, 50, and 100 mg/kg CeO2 NPs. The
results showed that CeO2 NPs accelerated the fresh biomass accumulation of radish
plant; especially in the treatment of 50 mg/kg CeO2 NPs, root expansion was
increased by 2.2 times as much as the control. In addition, the relative
chlorophyll content enhanced by 12.5, 12.9, and 12.2% was compared to control on
40 cultivation days. CeO2 NPs were mainly absorbed by the root and improved the
activity of antioxidant enzyme system to scavenge the damage of free radicals in
radish root and leaf. In addition, this study also indicated that the
nanoparticles might enter the food chain through the soil into the edible part of
the plant, which will be a potential threat to human health.
PMID- 28401393
TI - The role of forest in mitigating the impact of atmospheric dust pollution in a
mixed landscape.
AB - Atmospheric dust pollution, especially particulate matter below 2.5 MUm, causes
3.3 million premature deaths per year worldwide. Although pollution sources are
increasingly well known, the role of ecosystems in mitigating their impact is
still poorly known. Our objective was to investigate the role of forests located
in the surrounding of industrial and urban areas in reducing atmospheric dust
pollution. This was tested using lichen transplants as biomonitors in a
Mediterranean regional area with high levels of dry deposition. After a
multivariate analysis, we have modeled the maximum pollution load expected for
each site taking into consideration nearby pollutant sources. The difference
between maximum expected pollution load and the observed values was explained by
the deposition in nearby forests. Both the dust pollution and the ameliorating
effect of forested areas were then mapped. The results showed that forest located
nearby pollution sources plays an important role in reducing atmospheric dust
pollution, highlighting their importance in the provision of the ecosystem
service of air purification.
PMID- 28401394
TI - Revisiting inland hypoxia: diverse exceedances of dissolved oxygen thresholds for
freshwater aquatic life.
AB - Water resources in many regions are stressed by impairments resulting from
climate change, population growth and urbanization. In the United States (US),
water quality criteria (WQC) and standards (WQS) were established to protect
surface waters and associated designated uses, including aquatic life. In inland
waters of the south central US, for example, depressed dissolved oxygen (DO)
consistently results in impaired aquatic systems due to noncompliance with DO WQC
and WQS. In the present study, we systematically examined currently available DO
threshold data for freshwater fish and invertebrates and performed probabilistic
aquatic hazard assessments with low DO toxicity data that were used to derive the
US Environmental Protection Agency's (EPA) Ambient Water Quality Criteria (AWQC)
for DO and newly published information. Aquatic hazard assessments predicted
acute invertebrate DO thresholds for Ephemeroptera, Plecoptera, or Trichoptera
(EPT) taxa and species inhabiting lotic systems to be more sensitive than fish.
For example, these organisms were predicted to have acute low DO toxicity
thresholds exceeding the US EPA guidelines 17, 26, 31 and 38% and 13, 24, 30 and
39% of the time at 8.0, 5.0, 4.0 and 3.0 mg DO/L, respectively. Based on our
analysis, it appears possible that low DO effects to freshwater organisms have
been underestimated. We also identified influences of temperature on low DO
thresholds and pronounced differences in implementation and assessment of the US
EPA AWQC among habitats, seasons, and geographic regions. These results suggest
some implemented DO guidelines may adversely affect the survival, growth, and
reproduction of freshwater aquatic organisms in a region susceptible to climate
change and rapid population growth. Given the global decline of species,
particularly invertebrates, low DO threshold information, including sublethal
(e.g., reproduction, behavior) responses, for additional species (e.g., mollusks,
other invertebrates, warm water fish) across seasons, habitats, and life history
stages using consistent experimental designs is needed to support more
sustainable environmental assessment efforts and management of biodiversity
protection goals in inland waters.
PMID- 28401395
TI - Simultaneous wastewater treatment and bioelectricity production in microbial fuel
cells using cross-linked chitosan-graphene oxide mixed-matrix membranes.
AB - Microbial fuel cells (MFCs) are emerging technology for wastewater treatment by
chemical oxygen demand (COD) reduction and simultaneous bioelectricity
production. Fabrication of an effective proton exchange membrane (PEM) is a vital
component for MFC performance. In this work, green chitosan-based (CS) PEMs were
fabricated with graphene oxide (GO) as filler material (CS-GO) and cross-linked
with phosphoric acid (CS-GO-P(24)) or sulfuric acid (CS-GO-S(24)) to determine
their effect on PEM properties. Interrogation of the physicochemical, thermal,
and mechanical properties of the cross-linked CS-GO PEMs demonstrated that ionic
cross-linking based on the incorporation of PO43- groups in the CS-GO mixed
matrix composites, when compared with sulfuric acid cross-linking commonly used
in proton exchange membrane fuel cell (PEMFC) studies, generated additional
density of ionic cluster domains, rendered enhanced sorption properties, and
augmented the thermal and mechanical stability of the composite structure.
Consequently, bioelectricity performance analysis in MFC application showed that
CS-GO-P(24) membrane produced 135% higher power density than the CS-GO-S(24) MFC
system. Simultaneously, 89.52% COD removal of primary clarifier municipal
wastewater was achieved in the MFC operated with the CS-GO-P(24) membrane.
PMID- 28401396
TI - Applying the Temporal Abstraction Technique to the Prediction of Chronic Kidney
Disease Progression.
AB - Chronic kidney disease (CKD) has attracted considerable attention in the public
health domain in recent years. Researchers have exerted considerable effort in
attempting to identify critical factors that may affect the deterioration of CKD.
In clinical practice, the physical conditions of CKD patients are regularly
recorded. The data of CKD patients are recorded as a high-dimensional time
series. Therefore, how to analyze these time-series data for identifying the
factors affecting CKD deterioration becomes an interesting topic. This study aims
at developing prediction models for stage 4 CKD patients to determine whether
their eGFR level decreased to less than 15 ml/min/1.73m2 (end-stage renal
disease, ESRD) 6 months after collecting their final laboratory test information
by evaluating time-related features. A total of 463 CKD patients collected from
January 2004 to December 2013 at one of the biggest dialysis centers in southern
Taiwan were included in the experimental evaluation. We integrated the temporal
abstraction (TA) technique with data mining methods to develop CKD progression
prediction models. Specifically, the TA technique was used to extract vital
features (TA-related features) from high-dimensional time-series data, after
which several data mining techniques, including C4.5, classification and
regression tree (CART), support vector machine, and adaptive boosting (AdaBoost),
were applied to develop CKD progression prediction models. The results revealed
that incorporating temporal information into the prediction models increased the
efficiency of the models. The AdaBoost+CART model exhibited the most accurate
prediction among the constructed models (Accuracy: 0.662, Sensitivity: 0.620,
Specificity: 0.704, and AUC: 0.715). A number of TA-related features were found
to be associated with the deterioration of renal function. These features can
provide further clinical information to explain the progression of CKD. TA
related features extracted by long-term tracking of changes in laboratory test
values can enable early diagnosis of ESRD. The developed models using these
features can facilitate medical personnel in making clinical decisions to provide
appropriate diagnoses and improved care quality to patients with CKD.
PMID- 28401397
TI - Documentation and Treatment of Intraoperative Hypotension: Electronic Anesthesia
Records versus Paper Anesthesia Records.
AB - In this study, we examined anesthetic records before and after the implementation
of an electronic anesthetic record documentation (AIMS) in a single surgical
population. The purpose of this study was to identify any inconsistencies in
anesthetic care based on handwritten documentation (paper) or AIMS. We
hypothesized that the type of anesthetic record (paper or AIMS) would lead to
differences in the documentation and management of hypotension. Consecutive
patients who underwent esophageal surgery between 2009 and 2014 by a single
surgeon were eligible for the study. Patients were grouped in to 'paper' or
'AIMS' based on the type of anesthetic record identified in the chart. Pertinent
patient identifiers were removed and data collated after collection.
Predetermined preoperative and intraoperative data variables were reviewed.
Consecutive esophageal surgery patients (N = 189) between 2009 and 2014 were
evaluated. 92 patients had an anesthetic record documented on paper and 97 using
AIMS. The median number of unique blood pressure recordings was lower in the AIMS
group (median (Q1,Q3) AIMS 30.0 (24.0, 39.0) vs. Paper 35.0 (28.5, 43.5), p <
0.01). However, the median number of hypotensive events (HTEs) was higher in the
AIMS group (median (Q1,Q3) 8.0 (4.0, 18.0) vs. 4.0 (1.0, 10.5), p < 0.001), and
the percentage of HTEs per blood pressure recording was higher in the AIMS group
(30.4 ((Q1, Q3) (9.5, 60.9)% vs. 12.5 (2.4, 27.5)%), p < 0.01). Multivariable
regression analysis identified independent predictors of HTEs. The incidence of
HTEs was found to increase with AIMS (IRR = 1.88, p < 0.01). Preoperative
systolic blood pressure, increased blood loss, and phenylephrine. A phenylephrine
infusion was negatively associated with hypotensive events (IRR = 0.99, p =
0.03). We noted an increased incidence of HTEs associated with the institution of
an AIMS. Despite this increase, no change in medical therapy for hypotension was
seen. AIMS did not appear to have an effect on the management of intraoperative
hypotension in this patient population.
PMID- 28401398
TI - Evaluation of the Content of Antimony, Arsenic, Bismuth, Selenium, Tellurium and
Their Inorganic Forms in Commercially Baby Foods.
AB - Baby foods, from the Spanish market and prepared from meat, fish, vegetables,
cereals, legumes, and fruits, were analyzed to obtain the concentration of
antimony (Sb), arsenic (As), bismuth (Bi), and tellurium (Te) as toxic elements
and selenium (Se) as essential element. An analytical procedure was employed
based on atomic fluorescence spectroscopy which allowed to obtain accurate data
at low levels of concentration. Values of 14 commercial samples, expressed in
nanograms per gram fresh weight, ranged for Sb 0.66-6.9, As 4.5-242, Te 1.35
2.94, Bi 2.18-4.79, and Se 5.4-109. Additionally, speciation studies were
performed based on data from a non-chromatographic screening method. It was
concluded that tellurium and bismuth were mainly present as inorganic forms and
selenium as organic form, and antimony and arsenic species depend on the
ingredients of each baby food. Risk assessment considerations were made by
comparing dietary intake of the aforementioned elements through the consumption
of one baby food portion a day and recommended or tolerable guideline values.
PMID- 28401399
TI - Intelligent viewpoint selection for efficient CT to video registration in
laparoscopic liver surgery.
AB - PURPOSE: Minimally invasive surgery offers advantages over open surgery due to a
shorter recovery time, less pain and trauma for the patient. However, inherent
challenges such as lack of tactile feedback and difficulty in controlling
bleeding lower the percentage of suitable cases. Augmented reality can show a
better visualisation of sub-surface structures and tumour locations by fusing pre
operative CT data with real-time laparoscopic video. Such augmented reality
visualisation requires a fast and robust video to CT registration that minimises
interruption to the surgical procedure. METHODS: We propose to use view planning
for efficient rigid registration. Given the trocar position, a set of camera
positions are sampled and scored based on the corresponding liver surface
properties. We implement a simulation framework to validate the proof of concept
using a segmented CT model from a human patient. Furthermore, we apply the
proposed method on clinical data acquired during a human liver resection.
RESULTS: The first experiment motivates the viewpoint scoring strategy and
investigates reliable liver regions for accurate registrations in an intuitive
visualisation. The second experiment shows wider basins of convergence for higher
scoring viewpoints. The third experiment shows that a comparable registration
performance can be achieved by at least two merged high scoring views and four
low scoring views. Hence, the focus could change from the acquisition of a large
liver surface to a small number of distinctive patches, thereby giving a more
explicit protocol for surface reconstruction. We discuss the application of the
proposed method on clinical data and show initial results. CONCLUSION: The
proposed simulation framework shows promising results to motivate more research
into a comprehensive view planning method for efficient registration in
laparoscopic liver surgery.
PMID- 28401400
TI - Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease
models: evaluation of insulin and beta3-adrenergic receptor agonist effects by
18F-FDG.
AB - OBJECTIVE: One of the major causes of diabetes and obesity is abnormality in
glucose metabolism and glucose uptake in the muscle and adipose tissue based on
an insufficient action of insulin. Therefore, many of the drug discovery programs
are based on the concept of stimulating glucose uptake in these tissues.
Improvement of glucose metabolism has been assessed based on blood parameters,
but these merely reflect the systemic reaction to the drug administered. We have
conducted basic studies to investigate the usefulness of glucose uptake
measurement in various muscle and adipose tissues in pharmacological tests using
disease-model animals. METHODS: A radiotracer for glucose, 18F-2-deoxy-2-fluoro-D
glucose (18F-FDG), was administered to Wistar fatty rats (type 2 diabetes model),
DIO mouse (obese model), and the corresponding control animals, and the basal
glucose uptake in the muscle and adipose (white and brown) tissues were compared
using biodistribution method. Moreover, insulin and a beta3 agonist (CL316,243),
which are known to stimulate glucose uptake in the muscle and adipose tissues,
were administered to assess their effect. 18F-FDG uptake in each tissue was
measured as the radioactivity and the distribution was confirmed by
autoradiography. RESULTS: In Wistar fatty rats, all the tissues measured showed a
decrease in the basal level of glucose uptake when compared to Wistar lean rats.
On the other hand, the same trend was observed only in the white adipose tissue
in DIO mice, while brown adipose tissue showed increments in the basal glucose
uptake in this model. Insulin administration stimulated glucose uptake in both
Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty
rats. The same tendency was shown also in control mice, but clear increments in
glucose uptake were not observed in the muscle and brown adipose tissue of DIO
mice after insulin administration. beta3 agonist administration showed the
similar trend in Wistar lean and fatty rats as insulin, while the responses were
inhibited in the adipose tissues of Wistar fatty rats. CONCLUSION: A system to
monitor tissue glucose uptake with 18F-FDG enabled us to detect clear differences
in basal glucose uptake between disease-model animals and their corresponding
controls. The responses in the tissues to insulin or beta3 agonist could be
identified. Taken as a whole, the biodistribution method with 18F-FDG was
confirmed to be useful for pharmacological evaluation of anti-diabetic or anti
obesity drugs using disease-model animals.
PMID- 28401401
TI - Modulation of Tonic GABA Currents by Anion Channel and Connexin Hemichannel
Antagonists.
AB - Anion channels and connexin hemichannels are permeable to amino acid
neurotransmitters. It is hypothesized that these conductive pathways release
GABA, thereby influencing ambient GABA levels and tonic GABAergic inhibition. To
investigate this, we measured the effects of anion channel/hemichannel
antagonists on tonic GABA currents of rat hippocampal neurons. In contrast to
predictions, blockade of anion channels and hemichannels with NPPB potentiated
tonic GABA currents of neurons in culture and acute hippocampal slices. In
contrast, the anion channel/hemichannel antagonist carbenoxolone (CBX) inhibited
tonic currents. These findings could result from alterations of ambient GABA
concentration or direct effects on GABAA receptors. To test for effects on GABAA
receptors, we measured currents evoked by exogenous GABA. Coapplication of NPPB
with GABA potentiated GABA-evoked currents. CBX dose-dependently inhibited GABA
evoked currents. These results are consistent with direct effects of NPPB and CBX
on GABAA receptors. GABA release from hippocampal cell cultures was directly
measured using HPLC. Inhibition of anion channels with NPPB or CBX did not affect
GABA release from cultured hippocampal neurons. NPPB reduced GABA release from
pure astrocytic cultures by 21%, but the total GABA release from astrocytes was
small compared to that of mixed cultures. These data indicate that drugs commonly
used to antagonize anion channels and connexin hemichannels may affect tonic
currents via direct effects on GABAA receptors and have negligible effects on
ambient GABA concentrations. Interpretation of experiments using NPPB or CBX
should include consideration of their effects on tonic GABA currents.
PMID- 28401402
TI - Ischemia/Reperfusion-Induced Translocation of PKCbetaII to Mitochondria as an
Important Mediator of a Protective Signaling Mechanism in an Ischemia-Resistant
Region of the Hippocampus.
AB - Emerging reports indicate that activated PKC isoforms that translocate to the
mitochondria are pro- or anti-apoptotic to mitochondrial function. Here, we
concentrate on the role of PKCbeta translocated to mitochondria in relation to
the fate of neurons following cerebral ischemia. As we have demonstrated
previously ischemia/reperfusion injury (I/R) results in translocation of PKCbeta
from cytoplasm to mitochondria, but only in ischemia-resistant regions of the
hippocampus (CA2-4, DG), we hypothesize that this translocation may be a mediator
of a protective signaling mechanism in this region. We have therefore sought to
demonstrate a possible relationship between PKCbetaII translocation and ischemic
resistance of CA2-4, DG. Here, we reveal that I/R injury induces a marked
elevation of PKCbetaII protein levels, and consequent enzymatic activity, in CA2
4, DG in the mitochondrial fraction. Moreover, the administration of an isozyme
selective PKCbetaII inhibitor showed inhibition of I/R-induced translocation of
PKCbetaII to the mitochondria and an increase in neuronal death following I/R
injury in CA1 and CA2-4, DG in both an in vivo and an in vitro model of ischemia.
The present results suggest that PKCbetaII translocated to mitochondria is
involved in providing ischemic resistance of CA2-4, DG. However, the exact
mechanisms by which PKCbetaII-mediated neuroprotection is achieved are in need of
further elucidation.
PMID- 28401403
TI - Analysis of antimicrobial and immunomodulatory substances produced by
heterofermentative Lactobacillus reuteri.
AB - Antimicrobial and immunomodulatory potential of various Lactobacillus reuteri
strains is closely connected to their metabolite production profile under given
cultivation conditions. We determined the in vitro production of antimicrobial
substances such as organic acids, ethanol, and reuterin by four strains of L.
reuteri (L. reuteri E, L. reuteri KO5, L. reuteri CCM 3625, and L. reuteri ATCC
55730). All studied L. reuteri strains showed the ability to produce lactic acid,
acetic acid, and ethanol with concominant consumption of glucose and together
with phenyllactic acid-a potent antifungal compound-with concominant consumption
of phenylalanine. The reuterin production from glycerol was confirmed for all
analyzed lactobacilli strains except L. reuteri CCM 3625. Production of organic
acids, ethanol, and reuterin is significantly involved in antimicrobial activity
of lactobacilli which was determined using the dual-culture overlay diffusion
method against six indicator bacteria and five indicator moulds. In comparison to
the referential L. reuteri ATCC 55730, the highest inhibition potential was
observed against Escherichia coli CCM 3988 and Pseudomonas aeruginosa CCM 3955.
Among analyzed indicators of moulds, the growth of Alternaria alternata CCM F-128
was the most inhibited by all four analyzed L. reuteri strains. Finally, the
immunomodulatory potential of analyzed lactobacilli were proven by the
determination of the in vitro production of biogenic amines histamine and
tyramine. L. reuteri CCM 3625 was able to produce tyramine, and L. reuteri E and
L. reuteri KO5 were able to produce histamine under given cultivation conditions.
PMID- 28401404
TI - Controversy about Management of Hydrocephalus - Shunt vs. Endoscopic Third
Ventriculostomy.
AB - The best management of hydrocephalus is still controversial in the twenty-first
century. Shunt treatment for hydrocephalus is the most common procedure performed
in neurosurgical practice and is associated with the highest complications rate.
But during the last 2 decades, the treatment of hydrocephalus has improved with
better shunt devices available today, increased facilities for investigations and
newer approaches like endoscopic third ventriculostomy. The recent advances in
development of better endoscopes have provided the patient and treating doctor
with an option for an alternative surgery for treatment of hydrocephalus.
PMID- 28401405
TI - Patient choice modelling: how do patients choose their hospitals?
AB - As an aid to predicting future hospital admissions, we compare use of the
Multinomial Logit and the Utility Maximising Nested Logit models to describe how
patients choose their hospitals. The models are fitted to real data from
Derbyshire, United Kingdom, which lists the postcodes of more than 200,000
admissions to six different local hospitals. Both elective and emergency
admissions are analysed for this mixed urban/rural area. For characteristics that
may affect a patient's choice of hospital, we consider the distance of the
patient from the hospital, the number of beds at the hospital and the number of
car parking spaces available at the hospital, as well as several statistics
publicly available on National Health Service (NHS) websites: an average waiting
time, the patient survey score for ward cleanliness, the patient safety score and
the inpatient survey score for overall care. The Multinomial Logit model is
successfully fitted to the data. Results obtained with the Utility Maximising
Nested Logit model show that nesting according to city or town may be invalid for
these data; in other words, the choice of hospital does not appear to be preceded
by choice of city. In all of the analysis carried out, distance appears to be one
of the main influences on a patient's choice of hospital rather than statistics
available on the Internet.
PMID- 28401406
TI - The Impact of Militarism, Patriarchy, and Culture on Israeli Women's Reproductive
Health and Well-Being.
AB - PURPOSE: In this paper, we situate and frame Israeli women's reproductive health
within the social, historical, political, cultural, and geographical context of
Israeli women's lives. METHODS: We used a theoretical review in this paper.
RESULTS: Militarism, patriarchy, and cultural values heavily shape and influence
Jewish and Arab women's access to and experience of reproductive health when it
comes to the imperative to have children, pregnancy, birth, access to
contraception and abortion, and other reproductive healthcare services. We
discuss five main factors pertaining to Israeli women's reproductive health
including (1) fertility and emphasis on reproduction; (2) infertility; (3)
pregnancy, birth, and miscarriage; (4) reproductive rights including
contraception and abortion; and (5) maternity leave and accessible childcare.
CONCLUSIONS: Israel is a pro-natalist country, in which both Jewish and Arab
women share many of the consequences of the social imperative to have children.
Though Arab women, as part of their double minority status, are exposed to more
mental health risks pre- and postpartum, the personal and public reproductive
health decisions and reproductive healthcare services are largely shaped by
similar social forces. These include the patriarchal and religious culture that
dictates a value system that highly cherishes motherhood, and within the military
political context of the on-going Israeli-Palestinian conflict and past social
and political traumas. We address four major gaps that need to be addressed in
order to improve Israeli women's reproductive health and well-being that include
the neoliberal gap, the information gap, the reproductive health services gap,
and the leadership and policy gap.
PMID- 28401407
TI - Molecular analysis of amantadine-resistant influenza A (H1N1 pdm09) virus
isolated from slum dwellers of Dhaka, Bangladesh.
AB - Influenza is a highly contagious viral infection associated with excessive
hospitalizations and deaths throughout the world. Continuous antigenic shift and
drift is not only responsible for this devastating effect of influenza but also
causes ineffectiveness of antiviral drugs and vaccines. In this study, we
investigated the effectiveness of ribavirin, oseltamivir, and amantadine drugs in
vitro against nine influenza A isolates collected during June 2012-August 2013
from different slums in Dhaka city. The effectiveness of these drugs was
determined by measuring the inhibition of virus-induced cytopathic effect on MDCK
cells through MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide). Our data showed that all nine influenza isolates (6 H1N1 pdm09 and 3
H3N2 subtypes) were completely susceptible to ribavirin (The 50% effective
concentrations, EC50 3.0 ug/ml) and oseltamivir (EC50 0.35 ug/ml). When influenza
A infection was challenged with amantadine drug, eight out of nine isolates (88%)
demonstrated susceptibility to amantadine drug (EC50 0.30 ug/ml) while one H1N1
pdm09 isolate exhibited higher EC50 value (>10 ug/ml) beyond the cell tolerance
level of drug (>5 ug/ml). Genetic analysis of transmembrane matrix protein 2
(M2), which is a target for the amantadine drug and vital for viral replication,
showed a substitution of amino acid at position 31(S31 N) of that amantadine
resistant isolate indicating the possible reason of amantadine drug resistance.
PMID- 28401408
TI - Fluorescence Immunosensing of Insulin via Protein Functionalized Gold
Nanoclusters.
AB - A novel fluorescent immunosensor for the determination of insulin, an important
peptide hormone, has been fabricated in homogeneous solution. Bovine serum
albumin (BSA) capped gold nanoclusters (AuNCs), being highly biocompatible, were
used to label the insulin antibody (Ab). In presence of the target antigen,
insulin (Ag), specific immunoreaction between Ab and Ag takes place leading to
the fluorescence recovery of AuNCs that provided signal readout for the
immunosensing process. A linear relationship between the fluorescence signal and
concentration of insulin was obtained in the range of 4.9 * 10-9 g/mL to 3.8 * 10
8 g/mL, with a detection limit of 1.1 * 10-10 g/mL. Furthermore, application of
the present approach in human insulin injection and synthetic blood serum has
been demonstrated, thus promising an efficient platform for clinical diagnostics.
PMID- 28401409
TI - Furan and Julolidine-Based "Turn-on" Fluorescence Chemosensor for Detection of F-
in a Near-Perfect Aqueous Solution.
AB - A new fluorescent sensor 1, containing furan and julolidine moieties linked
through a Schiff-base, has been synthesized. Distinct "turn-on" fluorescence
enhancement of 1 was observed upon the addition of F- in a near-perfect aqueous
solution. The binding capabilities of 1 with F- were studied by using fluorescent
spectroscopic techniques, ESI-mass analysis and NMR titration measurements. The
detection limit for the analysis of F- was found to be 10.02 MUM, which is below
the WHO guideline (79 MUM) for drinking water. Practically, the sensing ability
of 1 for F- was successfully applied in real water samples. The sensing mechanism
for F- was proposed to be the ICT mechanism via the hydrogen bonding, which was
well explained by theoretical calculations.
PMID- 28401410
TI - A Dual-Readout Method for Biothiols Detection Based on the NSET of Nitrogen-Doped
Carbon Quantum Dots-Au Nanoparticles System.
AB - In this paper, a rapid, simple and highly sensitive method with dual-readout
(colorimetric and fluorometric) based on the nanometal surface energy transfer
(NSET) between nitrogen-doped carbon quantum dots (NCQDs) and gold nanoparticles
(AuNPs) for detection of biothiols is described. Highly luminescent NCQDs were
prepared via a simple one-step hydrothermal method by applying sucrose and
glycine as carbon and nitrogen sources. The results showed the obtained NCQDs had
an average particle diameter of 5 nm and highly luminescent. The maximum emission
wavelength was 438 nm with an excitation wavelength of 360 nm. In this system,
NCQDs and AuNPs were respectively treated as energy donors and energy acceptors,
which enable the nanometal surface energy transfer (NSET) from the NCQDs to the
AuNPs, quenching the fluorescence. However, biothiols was used as a competitor in
the NSET by the strongly Au-S bonding to release NCQDs from the Au surface, which
subsequently produces fluorescent signal recovery and the red-to-purple color
change quickly. This probe showed rapid response, high selectivity and
sensitivity for biothiols with dual colorimetric and fluorescent turn-on signal
changes. The low detection limit was calculated as 20 nM by using L-cysteine
acted as target melocules. The method was also successfully applied to the
determination of biothiols in human serum samples, and the results were
satisfying.
PMID- 28401411
TI - Fluorescence Detection of p-Nitrophenol in Water Using Bovine Serum Albumin
Capped ag Nanoclusters.
AB - We developed a sensitive and selective method for detection of 4-Nitrophenol
(PNP) using Ag nanoclusters (NCs) as fluorescence probe. Bovine serum albumin
(BSA) was used as the template for preparing Ag NCs via wet chemistry. The
fluorescence of as-prepared Ag NCs was significantly quenched in the presence of
PNP, showing excellent linear relationships between the quenching degree of the
fluorescence intensity and the concentrations of PNP in the range of 0.5 MUM to
60 MUM. The fluorescence quenching mechanism was also investigated. Furthermore,
this method was applied for the recognition of PNP in environmental samples.
PMID- 28401412
TI - Study of the Binding between Camptothecin Analogs and FTO by Spectroscopy and
Molecular Docking.
AB - In this work, the interaction between camptothecin (CPT) analogs and fat mass and
obesity associated (FTO) was investigated using spectroscopy and molecular
docking. From the experimental results, it was found that the CPT analogs caused
the fluorescence quenching of FTO through a static quenching procedure. The
binding constants and thermodynamic parameters at three different temperatures,
the number of binding sites were obtained, which suggested that the hydrophobic
interaction and electrostatic force played major role in the reaction between CPT
analogs and FTO. Results revealed that 10-hydroxycamptothecin was the strongest
quencher.
PMID- 28401413
TI - Concentration Dependent Approach for Accurate Determination of Two-Photon
Absorption Cross-Section of Fluorescent dye Molecule.
AB - We have investigated the concentration dependent of two-photon induced
fluorescence (TPIF) in methanolic solution of Rhodamine 6G and Rhodamine B dye
using 120 fs laser pulses at 780 nm, 76 MHz repetition rate. TPIF study of these
dyes was compared with their respective one photon fluorescence intensity. We
have shown the effect of chopper on TPIF intensity from Rhodamine dyes, which
have shown direct influence on the determined TPA Cross section of these dyes.
PMID- 28401414
TI - Getting to the Heart of Masculinity Stressors: Masculinity Threats Induce
Pronounced Vagal Withdrawal During a Speaking Task.
AB - BACKGROUND: Previous work has found that traditional masculinity ideals and
behaviors play a crucial role in higher rates of morbidity and mortality for men.
Some studies also suggest that threatening men's masculinity can be stressful.
Over time, this stress can weigh on men's cardiovascular and metabolic systems,
which may contribute to men's higher rates of cardiometabolic health issues.
PURPOSE: The purpose of this study is to explore how masculinity threats affect
men's heart rate and heart rate variability reactivity (i.e., vagal withdrawal)
to masculinity feedback on a social speaking task. METHODS: Two hundred and
eighty-five undergraduate males were randomly assigned to one of six conditions
during a laboratory-based speech task. They received one of two feedback types
(masculinity or control) and one of three feedback levels (low, high, or
dropping) in order to assess whether masculinity threats influence heart rate
reactivity and vagal withdrawal patterns during the speech task. RESULTS: Men who
receive low masculinity feedback during the speech task experienced more
pronounced vagal withdrawal relative to those who received the control.
CONCLUSION: Masculinity threats can induce vagal withdrawal that may accumulate
over the life course to contribute to men's relatively worse cardiometabolic
health.
PMID- 28401415
TI - Monitoring HIV Treatment and the Health Sector Cascade: From Treatment Numbers to
Impact.
AB - Although not originally part of the MDGs, HIV treatment has been at the center of
global HIV reporting since 2003, marked by achievement of the target of 15
million people receiving treatment before 2015 and 18.2 million (16.1-19.0
million) by mid 2016. Monitoring of treatment has been strengthened with
harmonized partner reporting and accountability with regular, annual reports.
Beyond treatment numbers, increasingly measures of treatment adherence, retention
and outcomes have been reported though with varying quality and completeness.
However, with the sustainable development goals (SDGs), monitoring treatment is
changing in three important ways. First, treatment monitoring is shifting from
numbers to coverage and gaps in a cascade of services to achieve universal
access. Secondly, this requires greater emphasis on disaggregated, individual
level patient and case monitoring systems, which can better support linkage,
retention and chronic, long term care. Thirdly, the prevention, testing and
treatment cascade with a clear results chain, links treatment numbers to impact,
in terms of reduced viral load, mortality and incidence. This agenda will require
a greater contribution of routine impact evaluation alongside monitoring, with
treatment seen as part of a cascade of services to ensure impact on mortality and
incidence. In conclusion, the shift from monitoring treatment numbers to
treatment linked to universal access to prevention, testing and treatment and
impact on mortality and incidence, will be critical to monitor, evaluate, and
improve HIV programs as part of the SDGs.
PMID- 28401416
TI - Supporting Shared Decision-making for Children's Complex Behavioral Problems:
Development and User Testing of an Option GridTM Decision Aid.
AB - There is a lack of research to guide collaborative treatment decision-making for
children who have complex behavioral problems, despite the extensive use of
mental health services in this population. We developed and pilot-tested a one
page Option GridTM patient decision aid to facilitate shared decision-making for
these situations. An editorial team of parents, child psychiatrists, researchers,
and other stakeholders developed the scope and structure of the decision aid.
Researchers included information about a carefully chosen number of psychosocial
and pharmacological treatment options, using descriptions based on the best
available evidence. Using semi-structured qualitative interviews (n = 18), we
conducted user testing with four parents and four clinical prescribers and field
testing with four parents, four clinical prescribers, and two clinic
administrators. The researchers coded and synthesized the interview responses
using mixed inductive and deductive methods. Parents, clinicians, and
administrators felt the Option Grid had significant value, although they reported
that additional training and other support would be required in order to
successfully implement the Option Grid and achieve shared decision-making in
clinical practice.
PMID- 28401417
TI - Effect of a comprehensive health education program on pre-hospital delay
intentions in high-risk stroke population and caregivers.
AB - OBJECTIVE: Many factors influence pre-hospital delays in the event of stroke.
This study aimed to develop and evaluate a comprehensive educational program for
decreasing pre-hospital delays in high-risk stroke population. METHODS: We
enrolled 220 high-risk stroke population and caregivers from six urban
communities in Harbin from May 2013 to May 2015, and randomly divided them into
intervention and control groups. We implemented a comprehensive educational
program (intervention group), comprising public lectures, instructional
brochures, case videos, simulations, and role-playing from May 2013 to May 2015.
We delivered conventional oral education in the control group. We compared stroke
pre-hospital delay behavioral intention (SPDBI), pre-hospital stroke symptom
coping test (PSSCT), and stroke pre-symptoms alert test (SPSAT) results between
the groups before and 6, 12, and 18 months after health intervention. RESULTS:
There were significant differences between before and after intervention (P <
0.01). SPDBI, PSSCT, and SPSAT scores were significantly different between the
groups (P < 0.01). The interaction between time and intervention method was
significant (P < 0.01). According to multivariate repeated measures analysis of
variance, SPDBI, PSSCT, and SPSAT scores were significantly different at each
time after intervention (P < 0.05). CONCLUSION: The comprehensive educational
program was significantly effective in decreasing SPDBI, improving knowledge,
enhancing stroke pre-symptoms alert, and reducing the possibility of pre-hospital
delays.
PMID- 28401418
TI - Development of a care guidance index based on what matters to patients.
AB - INTRODUCTION: Targeting resources for a designated higher-risk subgroup is a
strategy for chronic care management. However, risk-designation has several
limitations: it is inaccurate, seldom helpful for care guidance, and potentially
misallocates care away from many patients. METHODS: To address limitations of
risk designation, we tested a "what matters index" (WMI) in 19,593 adult patients
with chronic conditions. The WMI contains five binary measures: insufficient
confidence to manage health problems, level of pain, emotional problems,
polypharmacy, and adverse medication effects. We examined its sum for association
with patient-reported quality of life and prior emergency or hospital use. We
compared its accuracy to a prototypic risk-designation model. RESULTS: The WMI
was a good indicator for quality of life and in three diverse test populations it
was strongly associated with the use of hospital and emergency services. For
example, a sum of WMI >=2 was associated with twice as many average uses as none;
for >=3, uses were three times higher. However, since relatively few patients use
costly care, both the WMI and a prototypic risk-designation model had comparably
low-positive predictive values. The WMI uses the patient voice to identify needs
strongly associated with quality of life. Akin to risk designation models, the
WMI can be used to place patients into groups associated with levels of costly
services, but neither is likely to forecast costly service use for individuals.
However, unlike risk-designation models, the WMI is based on measures that will
immediately guide care for every patient.
PMID- 28401419
TI - The impact of quality-of-life data in relative effectiveness assessments of new
anti-cancer drugs in European countries.
AB - PURPOSE: The aim of this study is to investigate the role of health-related
quality-of-life (QoL) data in relative effectiveness assessments (REAs) of new
anti-cancer drugs across European jurisdictions, during health technology
assessment procedures. METHODS: Comparative analysis of guidelines and publicly
available REAs in six European jurisdictions of anti-cancer drugs approved by EMA
between 2011 and 2013. RESULTS: Fourteen anti-cancer drugs were included, adding
up to 79 REAs. Whilst all guidelines state that QoL is a relevant endpoint to
determine the relative effectiveness of new cancer drugs, QoL data were included
in only 54% of the 79 reports and their impact on the recommendations was
limited. CONCLUSIONS: Whilst national guidelines recognize the relevance of QoL
to determine the relative effectiveness of new anti-cancer drugs, this is not
well-reflected in current assessments. Developing and implementing into REAs
specific evidence requirements for QoL data would improve the use of this patient
centred outcome in future reimbursement and pricing decisions.
PMID- 28401420
TI - An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal
Osteomyelitis in Children.
AB - Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non
bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily
affects children. It is characterized by pain, local bone expansion, and
radiological findings suggestive of osteomyelitis, usually at multiple sites.
CRMO predominantly affects the metaphyses of long bones, but involvement of the
clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of
exclusion, and its pathogenesis remains unknown. Differential diagnosis includes
infection, malignancies, benign bone tumors, metabolic disorders, and other
autoinflammatory disorders. Biopsy of the bone lesion is not often required but
could be necessary in unclear cases, especially for differentiation from bone
neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line
treatment. Alternative therapies have been used, including corticosteroids,
methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-alpha inhibitors.
No guidelines have been established regarding diagnosis and treatment options.
This manuscript gives an overview of the most recent findings on the pathogenesis
of CRMO and clinical approaches for patients with the condition.
PMID- 28401421
TI - Redox Active Transition Metal ions Make Melanin Susceptible to Chemical
Degradation Induced by Organic Peroxide.
AB - With aging, retinal pigment epithelium melanosomes, by fusion with the age
pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin
granules may contain oxidized proteins and lipid hydroperoxides, which in
melanolipofuscin could chemically modify melanin polymer, while transition metal
ions present in melanin can accelerate such oxidative modifications. The aim of
this research was to examine the effect of selected transition metal ions on
melanin susceptibility to chemical modification induced by the water-soluble tert
butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by
DOPA autooxidation and melanosomes isolated from bovine retinal pigment
epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative
changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis
absorption spectroscopy, dynamic light scattering, atomic force microscopy and
electron paramagnetic resonance oximetry were employed. These measurements
revealed that both copper and iron ions accelerated chemical degradation induced
by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant
action was detected only in the case of melanosomes and melanin degraded in the
presence of iron. It can be postulated that similar chemical processes, if they
occur in situ in melanolipofuscin granules of the human retinal pigment
epithelium, would modify antioxidant properties of melanin and its reactivity.
PMID- 28401422
TI - Acetate-free biofiltration to remove fibroblast growth factor 23 in hemodialysis
patients: a pilot study.
AB - AIM: Serum levels of 32 kDa-phosphaturic hormone fibroblast growth factor 23
(FGF23) rise early in renal failure in order to keep phosphatemia within the
normal range; however, this compensatory mechanism itself contributes to chronic
kidney disease-mineral bone disorder. High FGF23 is also associated to left
ventricular hypertrophy, vascular calcifications and thus increased
cardiovascular risk. The aim of this pilot pre-post study was to evaluate the
effects of a single hemodiafiltration session with acetate-free biofiltration
(AFB) on FGF23 serum levels. METHODS: Nine hemodialysis patients were enrolled;
sessions were performed using the Integra(r) monitor (Hospal, Bologna, Italy) and
a polyacrylonitrile membrane. Peripheral venous blood samples were taken before
(pre-HD), at mid- and after treatment (post-HD); dialysate samples were collected
by the QuantiscanTM monitoring system. FGF23 was measured by a human FGF-23 ELISA
kit. Mid- and post-HD values were corrected for hemoconcentration. RESULTS: Pre
HD FGF23 levels positively correlated with dialysis vintage (r = 0.7192; p =
0.0443). They were significantly reduced by the hemodialysis session (from 2.38
+/- 1.80 to 1.15 +/- 1.21 ng/ml, p = 0.0171) with a reduction ratio of 52.55 +/-
28.76%. FGF23 was detected in the dialysate samples. CONCLUSION: FGF23 underwent
a significant reduction during AFB. Such removal was greater than that induced by
conventional hemodialysis as reported in the literature (19%-decrease using
modified cellulosic membranes). This difference may be attributed to the ability
of AFB hemodiafiltration to efficiently remove middle molecules by convection.
Whether a better clearance of FGF23 during hemodialysis may result in improved
cardiovascular outcomes in the long term needs to be confirmed by randomized
controlled trials.
PMID- 28401423
TI - In Favor of Disease Containment Rather than Grand Repair.
PMID- 28401424
TI - Hospital-Acquired Conditions Are Associated with Worse Outcomes in Crohn's
Disease-Related Hospitalizations.
AB - BACKGROUND: Crohn's disease (CD) is a chronically relapsing condition that
frequently requires hospitalization. In 2008, the Centers for Medicare and
Medicaid Services selected ten conditions that were deemed healthcare-acquired
conditions (HACs). Costs related to HACs are not reimbursed as they are
considered to be preventable. AIM: To determine the prevalence and impact of HACs
on hospital outcomes of hospitalized CD patients. METHODS: This was a cross
sectional study using data from the Nationwide Inpatient Sample between 2007 and
2011 with an extended time frame between 2002 and 2013 to specifically evaluate
the prevalence of HACs. CD-related hospitalizations and HACs were identified
using International Classification of Diseases, Ninth revision, Clinical
modification codes. The trend of HACs between 2002 and 2013 was assessed using a
Cochran-Armitage test. Primary outcomes, including hospital mortality, length of
stay, and hospital charges, were analyzed using univariate and multivariate
analyses. RESULTS: The prevalence of HACs initially increased between 2002 and
2008, remained stable between 2008 and 2011, than significantly decreased from
2011 to 2013. CD patients with HACs had higher hospital mortality, prolonged LOS,
and higher hospital charges compared to patients without HACs. CONCLUSIONS: The
prevalence of HACs among hospitalized CD patients initially increased from 2002
to 2008; however, rates began to decrease between 2011 and 2013. In addition,
HACs were associated with worse healthcare outcomes in hospitalized CD patients.
PMID- 28401425
TI - Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional
Imaging Predictors of Therapeutic Failure.
AB - BACKGROUND: Medical therapy efficacy remains controversial in stricturing Crohn's
disease. Cross-sectional imaging, especially magnetic resonance imaging, has been
suggested as very helpful to guide therapeutic decision making. AIM: To assess
efficacy and predictors of therapeutic failure in patients receiving medical
treatments for stricturing Crohn's disease. METHODS: In this retrospective study,
therapeutic failure was defined as symptomatic stricture leading to surgical or
endoscopic therapeutics, hospitalization, treatment discontinuation or additional
therapy and short-term clinical response as clinical improvement assessed by two
physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance
imaging and 22 CT scan) before starting medical therapy were analyzed
independently by two radiologists. Results were expressed as hazard ratio (HR) or
odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Among 84
patients, therapeutic failure rate within 60 months was 66.6%. In multivariate
analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37
11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80],
p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p =
0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were
associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI
[0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the
short-term clinical response rate was 65.7%. In multivariate analysis, male
gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09,
95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p =
0.047) were associated with short-term clinical failure. CONCLUSION: Anti-TNF
combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging
should be systematically performed to help medical management in stricturing
Crohn's disease.
PMID- 28401427
TI - Is there any role for thoracic ultrasound for interstitial lung disease
underlying rheumatologic conditions? Comment.
PMID- 28401426
TI - High Rates of Return to Sports Activities and Work After Osteotomies Around the
Knee: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Knee osteotomies are proven treatment options, especially in younger
patients with unicompartmental knee osteoarthritis, for certain cases of chronic
knee instability, or as concomitant treatment for meniscal repair or
transplantation surgery. Presumably, these patients wish to stay active. Data on
whether these patients return to sport (RTS) activities and return to work (RTW)
are scarce. OBJECTIVES: Our aim was to systematically review (1) the extent to
which patients can RTS and RTW after knee osteotomy and (2) the time to RTS and
RTW. METHODS: We systematically searched the MEDLINE and Embase databases. Two
authors screened and extracted data, including patient demographics, surgical
technique, pre- and postoperative sports and work activities, and confounding
factors. Two authors assessed methodological quality. Data on pre- and
postoperative participation in sports and work were pooled. RESULTS: We included
26 studies, involving 1321 patients (69% male). Mean age varied between 27 and 62
years, and mean follow-up was 4.8 years. The overall risk of bias was low in
seven studies, moderate in ten studies, and high in nine studies. RTS was
reported in 18 studies and mean RTS was 85%. Reported RTS in studies with a low
risk of bias was 82%. No studies reported time to RTS. RTW was reported in 14
studies; mean RTW was 85%. Reported RTW in studies with a low risk of bias was
80%. Time to RTW varied from 10 to 22 weeks. Lastly, only 15 studies adjusted for
confounders. CONCLUSION: Eight out of ten patients returned to sport and work
after knee osteotomy. No data were available on time to RTS. A trend toward
performing lower-impact sports was observed. Time to RTW varied from 10 to 22
weeks, and almost all patients returned to the same or a higher workload.
PMID- 28401429
TI - Learning at large conferences: from the 'sage on the stage' to contemporary
models of learning.
AB - AIM: To explore and evaluate the affordances of a flipped classroom model applied
to a research paper session within the professional development opportunity of a
large conference setting. METHOD: Authors were invited to present their research
papers in a flipped classroom presentation format at two large, multi-national
conferences. Before the session, authors and moderators met online to clarify
features of the session, and preparation of the material. The research material
was then posted online before the conference, to allow access by meeting
attendees. During the sessions, moderators encouraged the audience to actively
participate. An evaluation form was collected from the audience at the end of
each session. RESULTS: Participants found the session valuable, and appreciated
the opportunity to engage in a meaningful dialogue with colleagues. However, the
majority of the audience did not access the materials in advance. Lack of time,
or technology-related issues were mentioned as potential challenges to such
format. CONCLUSION: In the context of a large conference, a 'flipped session'
format can facilitate active learning and a participatory culture of inquiry.
However, to change the nature of how individuals learn collaboratively at large
conferences means a change in the culture of continuous professional learning.
PMID- 28401428
TI - Not all intermittent shakings are epilepsy.
PMID- 28401430
TI - Bilateral Effects of Excipients on Protein Stability: Preferential Interaction
Type of Excipient and Surface Aromatic Hydrophobicity of Protein.
AB - PURPOSE: Understanding the mechanism of protein-excipient interaction and
illuminating the influencing factors on protein stability are key steps in the
rational design of protein formulations. The objective of this study was to
assess effects of preferential interaction type of excipient and surface aromatic
hydrophobicity of protein on protein solution stability. METHODS: The
preferential interaction between excipient and aromatic hydrophobic area of
protein was investigated by solubility and fluorescence studies of amino acid
derivatives in excipient solutions. We examined conformational, colloidal and
mechanical stabilities of model proteins with different surface aromatic
hydrophobicities, including bovine serum albumin (BSA) and ovalbumin (OVA), and
then stability data were visualized by three-index empirical phase diagram.
RESULTS: The result showed that preferentially excluded excipients (trehalose,
sucrose and sorbitol) protected protein conformation against damage, but they
could accelerate mechanical stress-induced aggregation. Preferentially bound
excipients (propanediol and arginine) suppressed BSA aggregation, but arginine
failed to inhibit OVA aggregation, which might be attributed to the disparate
conformational perturbing effects of arginine on aromatic hydrophobic regions of
BSA and OVA. CONCLUSIONS: These findings provided strong evidence that excipient
possessed bilateral effects, and its application should be determined on
different preferential interaction behaviors of excipients with protein,
especially with the aromatic hydrophobic region.
PMID- 28401431
TI - Sustained Immunosuppression Alters Olfactory Function in the MRL Model of CNS
Lupus.
AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is
frequently accompanied by diverse neuropsychiatric manifestations. An increased
frequency of olfactory deficits has been recently reported as another marker of
CNS involvement in SLE patients. Similarly, we observed that spontaneous
development of lupus-like disease in MRL/lpr mice is accompanied by altered
olfaction-related behaviors. However, it remained unclear whether the behavioral
deficits are due to systemic autoimmunity, or the distinct genetic make-up. To
address this question, we presently examine whether prolonged treatment with the
immunosuppressive drug cyclophosphamide (CY) restores odor-guided behaviors in
MRL/lpr mice. Over 12 weekends, MRL/lpr and control MRL +/+ males were given ad
lib access to a sweetened CY solution or a vehicle. Their responsiveness to
different scents was assessed at ages corresponding to mild, modest, and severe
disease. Odor-guided exploratory behavior was further examined in the novel
object test at 21 weeks of age, shortly before terminal assessment of
immunopathology. In comparison to control groups, MRL/lpr mice exposed to CY
exhibited normal spleen size and antibody levels, as well as increased
responsiveness to an attractant and a novel object. However, CY treatment also
exacerbated their aberrant response to a repellent, suggesting a dual mode of
action on brain olfactory systems. The present results reveal that generalized
immunosuppression modulates odor-guided behaviors in lupus-prone animals.
Although key pathogenic mechanisms are not clear, the findings strengthen the
construct validity of the MRL model by supporting the hypothesis that onset of
systemic autoimmunity alters the activity of olfactory circuits.
PMID- 28401432
TI - Feasibility Assessment of a MALDI FTICR Imaging Approach for the 3D
Reconstruction of a Mouse Lung.
AB - Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS)
has proven to be a quick, robust, and label-free tool to produce two-dimensional
(2D) ion-density maps representing the distribution of a variety of analytes
across a tissue section of interest. In addition, three-dimensional (3D) imaging
mass spectrometry workflows have been developed that are capable of visualizing
these same analytes throughout an entire volume of a tissue rather than a single
cross-section. Until recently, the use of Fourier transform ion cyclotron
resonance (FTICR) mass spectrometers for 3D volume reconstruction has been
impractical due to software limitations, such as inadequate capacity to
manipulate the extremely large data files produced during an imaging experiment.
Fortunately with recent software and hardware advancements, 3D reconstruction
from MALDI FTICR IMS datasets is now feasible. Here we describe the first proof
of principle study for a 3D volume reconstruction of an entire mouse lung using
data collected on a FTICR mass spectrometer. Each lung tissue section was
analyzed with high mass resolution and mass accuracy, and considered as an
independent dataset. Each subsequent lung section image, or lung dataset, was
then co-registered to its adjacent section to reconstruct a 3D volume. Volumes
representing various endogenous lipid species were constructed, including
sphingolipids and phosphatidylcholines (PC), and species confirmation was
performed with on-tissue collision induced dissociation (CID). Graphical Abstract
?.
PMID- 28401433
TI - Nominal Mass?
AB - The current IUPAC-recommended definition of the term "nominal mass," based on the
most abundant naturally occurring stable isotope of an element, is flawed. We
propose that Nominal mass should be defined as the sum of integer masses of
protons and neutrons in any chemical species. In this way, all isotopes and
isotopologues can be assigned a definitive identifier. Graphical Abstract ?.
PMID- 28401435
TI - Erratum to: Anticipated Negative Police-Youth Encounters and Depressive Symptoms
among Pregnant African American Women: A Brief Report.
PMID- 28401434
TI - Long-term efficacy and safety of golimumab in the treatment of multirefractory
Behcet's disease.
AB - Our aim was to retrospectively assess the role of golimumab as a treatment choice
in patients with Behcet's disease (BD). Seventeen patients diagnosed with BD
according to the international criteria were consecutively enrolled; the BD
Current Activity Form (BDCAF) was used to evaluate disease activity. After having
collected clinical data from patients, statistical analysis was performed to
identify differences between the start of therapy and last visit; significance
was defined as p < 0.05. The mean duration of golimumab treatment was 18.47 +/-
20.8 months. At the time of data enrollment, 12/17 (70.6%) patients were still on
golimumab therapy. The mean time required to obtained clinical response was 4.9
+/- 5.7 weeks. At 3 months evaluation, golimumab was able to control BD-related
manifestations in 16/17 (94.1%) cases; the BDCAF values were significantly
decreased at the last follow-up compared to those assessed at the start of
golimumab (p = 0.002). The BDCAF improvement was significantly higher among
patients co-administered with DMARDs than those undergoing golimumab as
monotherapy (p = 0.048). At the last follow-up visit, corticosteroids had been
discontinued in 10 (58.8%) patients, while the corticosteroid dosage was
significantly lower at the last follow-up visit compared to the start of therapy
in those patients already on corticosteroids at the end of the study (p = 0.001).
Golimumab is a promising and safe treatment opportunity in BD patients with
different systemic involvement, inducing a prompt resolution of clinical
manifestations, a meaningful improvement of BDCAF score, and a significant
corticosteroid-sparing effect. However, golimumab co-administered with DMARDs has
provided better results than in patients undergoing monotherapy.
PMID- 28401436
TI - Cypress Pollinosis: from Tree to Clinic.
AB - Cypress (Cupressus sp.pl) is a genus within the Cupressaceae family. This family
covers all of the Earth's continents except for Antarctica, and it includes about
160 species. The most important taxa for allergic diseases belong to five
different genera: Cupressus, Hesperocyparis, Juniperus, Cryptomeria, and
Chamaecyparis. Cupressaceae species share a common pollen type that can even
include the genus Taxus (Taxaceae) when this plant is also present. As Juniperus
oxycedrus pollinates in October, Cupressus sempervirens in January and February,
Hesperocyparis arizonica (prev. Cupressus arizonica) in February and March, and
Juniperus communis in April, the symptomatic period is long-lasting. Due to
global warming, the pollination period tends to last longer, and there is a trend
for Cupressaceae bioclimate niches to migrate north. In Mediterranean areas, C.
sempervirens (Italian cypress or Mediterranean cypress) is by far the most common
pollinating species. It accounts for half of the total pollination level. The
group 1 major allergens belong to the pectate-lyase family, and members share 70
to 97% sequence homology within the different Cupressaceae. Group 2 allergens
correspond to the polygalacturonase protein family, while group 3, a minor
allergen, belongs to the family of "thaumatin-like proteins," a pathogenesis
related protein 5. Group 4 allergens are Ca++-binding protein (4 EF-hands). Aside
from these four groups, about 15 other allergens have been reported. Prominent
among these is a basic low-molecular mass cross-reactive allergen that was
identified recently, and which is suspected to be involved in pollen food
syndromes which are common with peach and citrus. The prevalence of cypress
allergy in the general population ranges from 0.6 to 3%, depending on the degree
of exposure to the pollen. Depending on the geographic area and the studied
population, 9 to 65% of outpatients consulting an allergist may have
sensitization to cypress pollen. Repeated cross-sectional studies performed at
different time intervals have demonstrated a threefold increase in the percentage
of cypress allergy around the Mediterranean area. Risk factors include a genetic
predisposition and/or a strong exposure to pollen, and the natural history of
cypress allergy allows identification of a subgroup of patients as allergic
rather than atopic. Concerning the clinical expression, rhinitis is the most
prevalent symptom, while conjunctivitis is the most disabling. Pharmacological
treatment of cypress allergies is not different from that of other seasonal
allergies. Immunotherapy has been used, initially by subcutaneous injections, but
currently mostly through the sublingual route. Although clinical trials have
included only a limited number of patients, it has proven effective and safe.
Avoidance can be implemented at the individual level, as well as at the community
level, through the use of alternative plants, low-pollinating cypresses, or by
trimming hedges before pollination.
PMID- 28401438
TI - Resveratrol induces mitochondrial dysfunction and decreases chronological life
span of Saccharomyces cerevisiae in a glucose-dependent manner.
AB - A broad range of health benefits have been attributed to resveratrol (RSV)
supplementation in mammalian systems, including the increases in longevity.
Nonetheless, despite the growing number of studies performed with RSV, the
molecular mechanism by which it acts still remains unknown. Recently, it has been
proposed that inhibition of the oxidative phosphorylation activity is the
principal mechanism of RSV action. This mechanism suggests that RSV might induce
mitochondrial dysfunction resulting in oxidative damage to cells with a
concomitant decrease of cell viability and cellular life span. To prove this
hypothesis, the chronological life span (CLS) of Saccharomyces cerevisiae was
studied as it is accepted as an important model of oxidative damage and aging. In
addition, oxygen consumption, mitochondrial membrane potential, and hydrogen
peroxide (H2O2) release were measured in order to determine the extent of
mitochondrial dysfunction. The results demonstrated that the supplementation of
S. cerevisiae cultures with 100 MUM RSV decreased CLS in a glucose-dependent
manner. At high-level glucose, RSV supplementation increased oxygen consumption
during the exponential phase yeast cultures, but inhibited it in chronologically
aged yeast cultures. However, at low-level glucose, oxygen consumption was
inhibited in yeast cultures in the exponential phase as well as in
chronologically aged cultures. Furthermore, RSV supplementation promoted the
polarization of the mitochondrial membrane in both cultures. Finally, RSV
decreased the release of H2O2 with high-level glucose and increased it at low
level glucose. Altogether, this data supports the hypothesis that RSV
supplementation decreases CLS as a result of mitochondrial dysfunction and this
phenotype occurs in a glucose-dependent manner.
PMID- 28401439
TI - Primary Extracranial Meningioma: A Rare Location.
AB - Meningiomas are benign extraaxial tumors of the central nervous system (CNS).
Extracranial meningiomas are extremely rare (2%) and can develop as a direct
extension from a primary intracranial meningioma or as true primary extracranial
meningioma originating from ectopic arachnoid cells. Only eight cases of primary
meningioma in the jaw have been reported to date. Extracranial meningiomas are
frequently misdiagnosed, resulting in inappropriate clinical management. The aim
of this article was to describe the case of a man with an asymptomatic swelling
in the right retromolar area over a period of 2 months. Cone beam computed
tomography was performed to determine the extension and involvement of the
adjacent structures. Histopathological findings and immunohistochemical analysis
aided in the diagnosis of primary extracranial meningioma in the mandible and
several aspects of this unusual neoplasm are reviewed. The treatment of choice
was a partial resection of the mandible and reconstruction with autogenous iliac
tricortical bone. Five years after surgery, the patient remains free of disease.
PMID- 28401440
TI - Coherence and content of relating emotions to life events in autism spectrum
disorder and typical development: a cross-sectional age study.
AB - Understanding one's own emotions is an important part of social-emotional
development in early childhood. Few studies have looked at the ability of
children with autism spectrum disorder (ASD) to relate their own emotions to
previous life events. Our previous study showed that the description of events
that elicited specific emotions is qualitatively and quantitatively different in
ASD in comparison to typically developing (TD) pre-adolescents. The current study
evaluated differences in coherence and content of responses to questions on
emotions in ASD and TD in two age groups. The evaluation was based on the section
on Emotions of the Autism Diagnostic Observation Schedule Module 3 test. The
study included 96 boys, 48 diagnosed with ASD (IQ>=85) and 48 TD children,
divided into younger (6:0-8:0y) and older (8:2-11:0y) groups. Young TD children
were able to give coherent responses to questions on experiences that evoked
basic emotions. Children with ASD gave fewer coherent responses and more 'no
response' and 'odd' responses across the examined age range. Only in the TD group
was the level of vocabulary associated with the number of coherent statements. TD
children gave more responses with content related to interpersonal relationships,
self-awareness and social events than children with ASD. Deficits in coherence
and content of responses to questions on emotions related to previous life events
derive from the core deficits of ASD. The significant quantitative and
qualitative gap that exists between ASD and TD may be useful during the
diagnostic process of ASD in childhood.
PMID- 28401437
TI - Estrogens regulate life and death in mitochondria.
AB - Estrogens coordinate and integrate cellular metabolism and mitochondrial
activities by direct and indirect mechanisms mediated by differential expression
and localization of estrogen receptors (ER) in a cell-specific manner. Estrogens
regulate transcription and cell signaling pathways that converge to stimulate
mitochondrial function- including mitochondrial bioenergetics, mitochondrial
fusion and fission, calcium homeostasis, and antioxidant defense against free
radicals. Estrogens regulate nuclear gene transcription by binding and activating
the classical genomic estrogen receptors alpha and beta (ERalpha and ERbeta) and
by activating plasma membrane-associated mERalpha, mERbeta, and G-protein coupled
ER (GPER, GPER1). Localization of ERalpha and ERbeta within mitochondria and in
the mitochondrial membrane provides additional mechanisms of regulation. Here we
review the mechanisms of rapid and longer-term effects of estrogens and selective
ER modulators (SERMs, e.g., tamoxifen (TAM)) on mitochondrial biogenesis,
morphology, and function including regulation of Nuclear Respiratory Factor-1
(NRF-1, NRF1) transcription. NRF-1 is a nuclear transcription factor that
promotes transcription of mitochondrial transcription factor TFAM (mtDNA
maintenance factorFA) which then regulates mtDNA-encoded genes. The nuclear
effects of estrogens on gene expression directly controlling mitochondrial
biogenesis, oxygen consumption, mtDNA transcription, and apoptosis are reviewed.
PMID- 28401441
TI - Effect of Inpatient Multicomponent Occupational Rehabilitation Versus Less
Comprehensive Outpatient Rehabilitation on Sickness Absence in Persons with
Musculoskeletal- or Mental Health Disorders: A Randomized Clinical Trial.
AB - Purpose To assess effects of an inpatient multicomponent occupational
rehabilitation program compared to less comprehensive outpatient rehabilitation
on sickness absence in persons with musculoskeletal- or mental health disorders.
Methods Randomized clinical trial with parallel groups. Participants were
individuals 18-60 years old on sick-leave for 2-12 months with a sick-leave
diagnosis within the musculoskeletal, psychological or general and unspecified
chapters of ICPC-2, identified in a national register. The inpatient program (4 +
4 days) consisted of Acceptance and Commitment Therapy (ACT), physical training
and work-related problem-solving including creating a return to work plan and a
workplace visit if considered relevant. The outpatient program consisted
primarily of ACT (6 sessions during 6 weeks). Both programs were group based.
Primary outcome was cumulated number of sickness absence days at 6 and 12 months
follow-up. Secondary outcome was time until sustainable return to work. Results
168 individuals were randomized to the inpatient program (n = 92) or the
outpatient program (n = 76). We found no statistically significant difference
between the programs in median number of sickness absence days at 6 and 12 months
follow-up. In the outpatient program 57% of the participants achieved sustainable
return to work (median time 7 months), in the inpatient program 49% (log rank, p
= 0.167). The hazard ratio for sustainable return to work was 0.74 (95% CI 0.48
1.32, p = 0.165), in favor of the outpatient program. Conclusions This study
provided no support that the more comprehensive 4 + 4 days inpatient
multicomponent occupational rehabilitation program reduced sickness absence
compared to the outpatient rehabilitation program.
PMID- 28401442
TI - Erratum to: Chronic hyperglycemia affects bone metabolism in adult zebrafish
scale model.
PMID- 28401443
TI - Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and
prostate cancer treated with ipilimumab.
AB - OBJECTIVE: Ipilimumab is a human monoclonal antibody directed against cytotoxic T
lymphocyte antigen-4, that has been shown to significantly improve survival in
patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4
elicits T cell activation, proliferation and anti-tumor response, but can also
trigger immune-related adverse events. Among immune-related endocrinopathies,
hypophysitis represents the most frequent, with an incidence up to 17% in
patients treated with ipilimumab. DESIGN AND METHODS: We report nine cases of
ipilimumab-induced hypophysitis in a cohort of 273 patients treated with
ipilimumab between 2006 and 2015, as part of clinical trials or after its
marketing. Thyroid function tests were scheduled at screening and during follow
up (every 21 days) in all patients. Cortisol, adrenocorticotropic hormone,
follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or
testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1
were measured only in case of clinical suspicion. RESULTS: The incidence of
hypophysitis was 3.3%. The most frequent pituitary failure was
adrenocorticotropic hormone and thyroid stimulating hormone secretion with a
complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic
hormone during follow up. All patients had negative pituitary antibodies. The
main symptoms at diagnosis were fatigue and headache. CONCLUSION: Clinicians
should be aware about the risk of hypophysitis during treatment with immune check
point inhibitors and the necessity of investigating pituitary function during
therapy. Pituitary magnetic resonance imaging does not seem pivotal for a
definite diagnosis if not performed at the onset of disease.
PMID- 28401444
TI - Fixed ratio combinations of glucagon like peptide 1 receptor agonists with basal
insulin: a systematic review and meta-analysis.
AB - PURPOSE: Basal insulin controls primarily fasting plasma glucose but causes
hypoglycaemia and weight gain, whilst glucagon like peptide 1 receptor agonists
induce weight loss without increasing risk for hypoglycaemia. We conducted a
systematic review and meta-analysis of randomised controlled trials to
investigate the efficacy and safety of fixed ratio combinations of basal insulin
with glucagon like peptide 1 receptor agonists. METHODS: We searched Medline,
Embase, and the Cochrane Library as well as conference abstracts up to December
2016. We assessed change in haemoglobin A1c, body weight, and incidence of
hypoglycaemia and gastrointestinal adverse events. RESULTS: We included eight
studies with 5732 participants in the systematic review. Switch from basal
insulin to fixed ratio combinations with a glucagon like peptide 1 receptor
agonist was associated with 0.72% reduction in haemoglobin A1c [95% confidence
interval -1.03 to -0.41; I 2 = 93%] and 2.35 kg reduction in body weight (95%
confidence interval -3.52 to -1.19; I 2 = 93%), reducing also risk for
hypoglycaemia [odds ratio 0.70; 95% confidence interval 0.57 to 0.86; I 2 = 85%]
but increasing incidence of nausea (odds ratio 6.89; 95% confidence interval 3.73
12.74; I 2 = 79%). Similarly, switching patients from treatment with a glucagon
like peptide 1 receptor agonist to a fixed ratio combination with basal insulin
was associated with 0.94% reduction in haemoglobin A1c (95% confidence interval
1.11 to -0.77) and an increase in body weight by 2.89 kg (95% confidence interval
2.17-3.61). CONCLUSIONS: Fixed ratio combinations of basal insulin with glucagon
like peptide 1 receptor agonists improve glycaemic control whilst balancing out
risk for hypoglycaemia and gastrointestinal side effects.
PMID- 28401446
TI - Liposomal Irinotecan: A Review in Metastatic Pancreatic Adenocarcinoma.
AB - Intravenous liposomal irinotecan injection (Onivyde(r)) is approved for use in
combination with 5-fluorouracil and leucovorin (5-FU/LV) in patients with
metastatic pancreatic adenocarcinoma that has progressed following gemcitabine
based therapy. Liposomal irinotecan is a liposome-encapsulated formulation of the
topoisomerase-1 inhibitor irinotecan, developed to overcome the pharmacological
and clinical limitations of non-liposomal irinotecan. In the pivotal
multinational, phase III NAPOLI-1 trial in patients with metastatic pancreatic
adenocarcinoma that had progressed following gemcitabine-based therapy, liposomal
irinotecan in combination with 5-FU/LV significantly prolonged median overall
survival (OS; primary endpoint) and median progression-free survival (PFS) at the
time of the primary analysis (after 313 events) and final analysis (after 382
events) compared with 5-FU/LV control therapy. The objective response rate was
also significantly higher in the liposomal irinotecan plus 5-FU/LV group than in
the control group. Liposomal irinotecan-based combination therapy had a
manageable safety profile; the most common treatment-emergent adverse events
(TEAEs) of grade >=3 severity were haematological or gastrointestinal in nature.
The incidence of neutropenic sepsis was low. In a setting where there is a
paucity of second-line treatment options, liposomal irinotecan in combination
with 5-FU/LV is an important emerging treatment option for metastatic
adenocarcinoma of the pancreas that has progressed following gemcitabine-based
therapy.
PMID- 28401447
TI - Infection Control in Limited Resources Countries: Challenges and Priorities.
AB - PURPOSE OF REVIEW: The purpose of this article is to review the current status of
health care-related infections (HCRI) in low- and middle-income countries (LMIC).
RECENT FINDINGS: HCRI in LMIC are being recognized as an important health problem
globally. Despite important efforts, complex medical and non-medical problems
prevail. The HCRI burden in LMIC is bigger than in developed countries, with
prevalence between 5.7 and 19.1%. The impact on patients, their families, and the
hospital systems is high, but has been largely underestimated. During the last 30
years, some progress has been made, with an increased awareness from the medical
community and some very successful programs; however, there is a huge gap for
improvement and success. In many health care facilities, there is a need of
functional surveillance programs, continuous supply of antiseptics, safe water
supply, personal protective equipment, essential antibiotics to treat infections,
appropriate number of health care personnel trained in infection control, and
appropriate health care infrastructure and political commitment.
PMID- 28401448
TI - The Changing Epidemiology of Infective Endocarditis in the Twenty-First Century.
AB - PURPOSE OF THE REVIEW: Infective endocarditis (IE) is a relatively infrequent
infectious disease. It does, however, causes serious morbidity, and its mortality
rate has remained unchanged at approximately 25%. Changes in IE risk factors have
deeply impacted its epidemiology during recent decades but literature from low
income countries is very scarce. Moreover, prophylaxis guidelines have recently
changed and the impact on IE incidence is still unknown. RECENT FINDINGS: In high
income countries, the proportion of IE related to prior rheumatic disease has
decreased significantly and has been replaced proportionally by cases related to
degenerative valvulopathies, prosthetic valves, and cardiovascular implantable
electronic devices. Nosocomial and non-nosocomial-acquired cases have risen, as
has the proportion caused by staphylococci, and the median age of patients. In
low-income countries, in contrast, rheumatic disease remains the main risk
factor, and streptococci the most frequent causative agents. Studies performed to
evaluate impact of guidelines changes' have shown contradictory results. The
increased complexity of cases in high-income countries has led to the creation of
IE teams, involving several specialties. New imaging and microbiological
techniques may increase sensitivity for diagnosis and detection of IE cases. In
low-income countries, IE remained related to classic risk factors. The
consequences of prophylaxis guidelines changes are still undetermined.
PMID- 28401445
TI - Pharmacotherapeutic Targeting of G Protein-Coupled Receptors in Oncology:
Examples of Approved Therapies and Emerging Concepts.
AB - G protein-coupled receptors (GPCRs) are involved in numerous physio-pathological
processes, including the stimulation of cancer progression. In this regard, it
should be mentioned that although GPCRs may represent major pharmaceutical
targets, only a few drugs acting as GPCR inhibitors are currently used in anti
tumor therapies. For instance, certain pro-malignancy effects mediated by GPCRs
are actually counteracted by the use of small molecules and peptides that
function as receptor antagonists or inverse agonists. Recently, humanized
monoclonal antibodies targeting GPCRs have also been developed. Here, we review
the current GPCR-targeted therapies for cancer treatment, summarizing the
clinical studies that led to their official approval. We provide a broad overview
of the mechanisms of action of the available anti-cancer drugs targeting
gonadotropin-releasing hormone, somatostatin, chemokine, and Smoothened
receptors. In addition, we discuss the anti-tumor potential of novel non-approved
molecules and antibodies able to target some of the aforementioned GPCRs in
different experimental models and clinical trials. Likewise, we focus on the
repurposing in cancer patients of non-oncological GPCR-based drugs, elucidating
the rationale behind this approach and providing clinical evidence on their
safety and efficacy.
PMID- 28401449
TI - Silence of Long Noncoding RNA NEAT1 Inhibits Malignant Biological Behaviors and
Chemotherapy Resistance in Gastric Cancer.
AB - Gastric cancer (GC) is the most common solid tumor in digestive system. Nuclear
enriched abundant transcript 1 (NEAT1) gene is a lncRNA, and reveal potential
oncogene role in several malignant tumors. The aim of this study is to
investigate the expression and clinical significance of Nuclear Paraspeckle
Assembly Transcript 1 (NEAT1) gene and its influence to malignant biologic
behaviors and chemotherapy resistance to adriamycin in GC. This study found NEAT1
was up-regulated in GC tissues and cells, especially in in GC adriamycin
resistant cells. NEAT1 silence in SGC7901 cells could inhibit proliferation and
invasion ability, and promote cell apoptosis significantly. NEAT1 silence in
adriamycin-resistant SGC7901/ADR cells also depressed the half maximal inhibitory
concentration (IC50) for adriamycin, chemotherapy resistance to adriamycin was
inhibited significantly. NEAT1 knockdown promoted apoptosis in SGC7901/ADR cells
induced by adriamycin. In summary, lncRNA NEAT1 is high-expressed in GC and
functions as an oncogene to modulate apoptosis, invasion, proliferation and
chemotherapy resistance of GC cells, which might be a novel potential therapeutic
target for GC.
PMID- 28401450
TI - Reproducibility and Prognostic Potential of Ki-67 Proliferation Index when
Comparing Digital-Image Analysis with Standard Semi-Quantitative Evaluation in
Breast Cancer.
AB - In this study, the reproducibility of Ki-67 proliferation index (KIPI) was
investigated by comparing the semi-quantitative (SQ) results of three assessors
with those of digital image-analysis (DIA) methods. The prognostic significance
of the two approaches was also correlated with clinical outcome. Tissue
microarrays of duplicate 2 mm cores were constructed from representative areas of
formalin-fixed and paraffin-embedded tumor blocks of 347 breast cancer patients.
SQ evaluation of Ki-67 (MIB1 clone) immunostained slides was performed
independently by three pathologists. DIA was completed using a fully automated
histological pattern and cell recognition module for KIPI detection (DIA-1) and
an adjustable module (DIA-2) with the possibility of manual corrections. To
compare SQ and DIA evaluations intra-class correlation (ICC) and concordance
correlation coefficients (CCC) were determined. The three SQ evaluations
demonstrated a remarkable ICC (0.853). Significant difference and poor
concordance occurred between SQ-1 and SQ-2 as well as between SQ-1 and SQ-3 (p <=
0.001, CCC <= 0.827 for both comparisons). Thus, the reference KIPI value (SQ-RV)
was generated from the mean values of SQ-2 and SQ-3. SQ-RV and DIA-2 results
showed substantial concordance (CCC = 0.963, at p = 0.754), while SQ-RV and DIA-1
values differed (p <= 0.001) at only moderate concordance (CCC = 0.906). In
multivariate analysis, lymph node status and SQ-2 assessment were significantly
associated with clinical outcome (p <= 0.012 for both comparisons). Our results
confirm that KIPI is a significant prognostic marker in breast cancer, which can
be can be reliably reproduced by using an adjustable DIA-2 image analysis module.
PMID- 28401451
TI - COL1A2 is a Novel Biomarker to Improve Clinical Prediction in Human Gastric
Cancer: Integrating Bioinformatics and Meta-Analysis.
AB - Gastric cancer is the third most common cause of cancer-related death in
worldwide. It is crucial to target the key genes controlling pathogenesis in the
early stage of gastric cancer. This study describes an integrated bioinformatics
to identify molecular biomarkers for gastric cancer in patients' cancer tissues.
We reports differently expression genes in large gastric cancer cohorts from Gene
Expression Ominus (GEO). Our findings revealed that 433 genes were significantly
different expressed in human gastric cancer. Differently expression gene profile
in gastric cancer was further validated by bioinformatic analyses, co-expression
network construction. Based on the co-expression network and top-ranked genes, we
identified collagen type I alpha 2 (COL1A2) which encodes the pro-alpha2 chain of
type I collagen whose triple helix comprises two alpha1 chains and one alpha2
chain, was the key gene in a 37-gene network that modulates cell motility by
interacting with the cytoskeleton. Furthermore, the prognostic role of COL1A2 was
determined by use of immunohistochemistry on human gastric cancer tissue. COL1A2
was highly expressed in human gastric cancer as compared with normal gastric
tissues. Statistical analysis showed COL1A2 expression level was significantly
associated with histological type and lymph node status. However, there were no
correlations between COL1A2 expression and age, lymph node numbers, tumor size,
or clinical stage. In conclusion, the novel bioinformatics used in this study has
led to identification of improving diagnostic biomarkers for human gastric cancer
and could benefit further analyses of the key alteration during its progression.
PMID- 28401453
TI - Erratum to: Adding Prandial Insulin to Basal Insulin Plus Oral Antidiabetic Drugs
in Chinese Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open
Label, Single-Arm Study.
PMID- 28401452
TI - Polymorphism of Promoter Region of TNFRSF1A Gene (-610 T > G) as a Novel
Predictive Factor for Radiotherapy Induced Oral Mucositis in HNC Patients.
AB - Every year, about 650 thousand new cases of Head and Neck Cancer (HNC) are
diagnosed globally. Apart from surgery, radiotherapy (RTH), chemotherapy (CHT) or
its combination is used in the treatment of HNC. One of the most frequent
complications and, at the same time, limitations of RTH is oral mucositis (OM).
Proinflammatory cytokines (including TNF-alpha) play a key role in the
development of OM. Genetic alterations, i.e. single nucleotide polymorphisms
(SNPs) within genes encoding for receptors for TNF (ie. TNFRSF1A) may change
their function. The aim of this study was to investigate relationship between a
polymorphism of TNFRSF1A and occurrence and severity of acute reaction after RTH
for HNC patients. Data from 58 HNC patients (stages I-IV) were analyzed. All of
them were irradiated using IMRT technique with doses 50-70Gy. Oral mucositis (OM)
was evaluated according to RTOG/EORTC guidelines. DNA from HNC patients were
isolated from whole blood and genotypes were determined by sequencing method.
Patients with TT or GT genotype demonstrated higher risk of manifestation of
grade 3 OM in 5th week of RTH (p=0.041; OR=9.240; 95% CI: 1.101-77.581) compared
to GG carriers. Similarly, high risk of grade 3 OM in patients with T allele
presence was noted in 6th week (p=0.030; OR=10.50; 95%CI:1.257-87.690) and in 7th
week (p=0.008; OR=5.625; 95% CI: 1.584-19.975) of treatment compared to patients
with GG homozygote. Our results indicate an association between SNP of TNFRSF1A
(rs4149570) gene and risk of more severe OM related to radiation therapy for HNC
patients.
PMID- 28401454
TI - Use of Flash Glucose-Sensing Technology for 12 months as a Replacement for Blood
Glucose Monitoring in Insulin-treated Type 2 Diabetes.
AB - INTRODUCTION: Published evaluations of sensor glucose monitoring use in insulin
treated type 2 diabetes are limited. The aim of this study was to assess the
impact of flash glucose-sensing technology as a replacement for self-monitoring
of blood glucose (SMBG) over a 12-month period in participants with type 2
diabetes who were on intensive insulin therapy. METHODS: An open-label,
randomized, controlled study in adults with type 2 diabetes on intensive insulin
therapy from 26 European diabetes centers aimed at assessing flash glucose
sensing technology was conducted. Participants (N = 224) were randomized (1:2
respectively) to a control group (n = 75) that used SMBG (FreeStyle LiteTM) or to
an intervention group (n = 149) which used sensor glucose data (FreeStyle LibreTM
Flash Glucose Monitoring System) for self-management over 6 months. All
intervention group participants who completed the 6-month treatment phase
continued into an additional 6-month open-access phase. RESULTS: A total of 139
intervention participants completed the 6-month treatment phase and continued
into the open-access phase. At 12 months (end of open-access period), time in
hypoglycemia [sensor glucose <3.9 mmol/L (70 mg/dL)] was reduced by 50% compared
to baseline [-0.70 +/- 1.85/24 h (mean +/- standard deviation); p = 0.0002].
Nocturnal hypoglycemia [2300 to 0600 hours, <3.9 mmol/L (70 mg/dL)] was reduced
by 52%; p = 0.0002. There was no change in time in range [sensor glucose 3.9-10.0
mmol/L (70-180 mg/dL)]. SMBG testing fell from a mean of 3.9 (median 3.9)
times/day at baseline to 0.2 (0.0), with an average frequency of sensor scanning
of 7.1 (5.7) times/day at 12 months, and mean sensor utilization was 83.6 +/-
13.8% (median 88.3%) during the open-access phase. During this 6-month extension
period no device-related serious adverse events were reported. Nine participants
reported 16 instances of device-related adverse events (e.g. infection, allergy)
and 28 participants (20.1%) experienced 134 occurrences of anticipated skin
symptoms/sensor-insertion events expected with device use (e.g. erythema, itching
and rash). CONCLUSION: The use of flash glucose-sensing technology for glycemic
management in individuals with type 2 diabetes treated by intensive insulin
therapy over 12 months was associated with a sustained reduction in hypoglycemia
and safely and effectively replaced SMBG. TRIAL REGISTRATION: ClinicalTrials.gov
identifier, NCT02082184.
PMID- 28401456
TI - Cardiovascular Complications Associated With Novel Cancer Immunotherapies.
AB - OPINION STATEMENT: Immune therapies represent a quantum leap in the fight against
cancer. Recently approved immune checkpoint inhibitors that target receptors
involved in immune escape of cancer cells (including cytotoxic T lymphocyte
associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and
programmed cell death protein ligand-1 (PD-L1) are increasingly being used for
therapeutic benefit in a number of cancers. The robust anti-cancer activity of
these agents has been accompanied by the recognition of new adverse effects,
often due to the over activation of immune system, that may limit their
therapeutic benefit and adversely impact outcomes. Combination treatments in
particular, such as approaches using two targeted immunotherapy agents, have
higher risk of adverse effects. Our review focuses on the approved checkpoint
inhibitor therapies and their potential for cardiovascular toxicity. While very
few cases of autoimmune cardiotoxicity and myocarditis have been reported in
clinical trials, severe, life-threatening episodes of heart failure and
hemodynamic compromise associated with the use of immune checkpoint inhibitors
have recently been reported in the literature. Early recognition, diagnosis, and
management of autoimmune myocarditis represent an important clinical challenge
with no current guidelines available for prevention, identification, and
treatment of this serious condition. This area of cardio-oncology is evolving
rapidly as more drugs in this class are being discovered and pending approval.
There is a need for future studies focused on prospective identification of
biomarkers and clinical standards for treatment and long-term follow-up of
cardiovascular toxicity to successfully continue the treatment of cancer while
preventing the adverse outcomes with novel immune therapies.
PMID- 28401455
TI - What Is the Appropriate Lesion Set for Ablation in Patients with Persistent
Atrial Fibrillation?
AB - OPINION STATEMENT: Special attention must be paid to detect, diagnose, and
optimize management of reversible or treatable causes of long-standing persistent
atrial fibrillation (LSPAF) such as obesity, obstructive sleep apnea (OSA),
hypertension, hypo or hyperthyroidism, inflammatory and infectious diseases, and
stress. Though, we strongly believe that the role of the pulmonary veins (PVs) is
more pronounced in paroxysmal atrial fibrillation (AF) than in persistent AF,
performing an adequate pulmonary vein isolation is still key in LSPAF. Patients
with LSPAF will frequently require a more aggressive mapping and ablative
approach. We do not encourage the use of empiric lines or complex fractionated
atrial electrograms. Ablation of sites associated with non-PV triggers such as
the entire posterior wall, the roof, the anterior part of the left atrium septum,
left atrial appendage (LAA), the CS and SVC has been shown to improve the freedom
from AF at follow-up when combined with PVs isolation. During the isoproterenol
challenge, non-PV triggers are detected in most patients with AF. Mapping non-PV
triggers is guided by multiple catheters positioned along both the right and left
atriums: a 10-pole circular mapping catheter in the left superior PV recording
the far-field LAA activity, the ablation catheter in the right superior PV that
records the far-field interatrial septum and a 20-pole catheter with electrodes
spanning from the SVC to the CS. With this simple catheter setup, when focal
ectopic atrial activity is observed (a single ectopic beat is enough) their
activation sequence is compared to that of sinus rhythm, allowing to quickly
identify their area of origin. For significant non-PV triggers (repetitive
isolated beats, focal atrial tachycardias or beats triggering AF/atrial flutter,
a more detailed activation mapping is performed in the area of origin. They are
subsequently targeted with focal ablation, exception being the triggers
originating from the SVC, LAA or CS, in which cases complete isolation of these
structures is the ablation strategy of choice. We truly believe the LAA deserves
special consideration when managing patients with persistent AF and LSPAF.
PMID- 28401457
TI - Comparative studies of vertebrate iduronate 2-sulfatase (IDS) genes and proteins:
evolution of A mammalian X-linked gene.
AB - IDS is responsible for the lysosomal degradation of heparan sulfate and dermatan
sulfate and linked to an X-linked lysosomal storage disease,
mucopolysaccharidosis 2 (MPS2), resulting in neurological damage and early death.
Comparative IDS amino acid sequences and structures and IDS gene locations were
examined using data from several vertebrate genome projects. Vertebrate IDS
sequences shared 60-99% identities with each other. Human IDS showed 47% sequence
identity with fruit fly (Drosophila melanogaster) IDS. Sequence alignments, key
amino acid residues, N-glycosylation sites and conserved predicted secondary and
tertiary structures were also studied, including signal peptide, propeptide and
active site residues. Mammalian IDS genes usually contained 9 coding exons. The
human IDS gene promoter contained a large CpG island (CpG46) and 5 transcription
factor binding sites, whereas the 3'-UTR region contained 5 miRNA target sites.
These may contribute to IDS gene regulation of expression in the brain and other
neural tissues of the body. An IDS pseudogene (IDSP1) was located proximally to
the IDS gene on the X-chromosome in primate genomes. Phylogenetic analyses
examined the relationships and potential evolutionary origins of the vertebrate
IDS gene. These suggested that IDS has originated in an invertebrate ancestral
genome and retained throughout vertebrate evolution and conserved on marsupial
and eutherian X-chromosomes, with the exception of rat Ids on chromosome 8.
PMID- 28401458
TI - Purification, characterization and thermostability improvement of xylanase from
Bacillus amyloliquefaciens and its application in pre-bleaching of kraft pulp.
AB - Xylanases have important industrial applications but are most extensively
utilized in the pulp and paper industry as a pre-bleaching agent. We
characterized a xylanase from Bacillus amyloliquefaciens strain SK-3 and studied
it for kraft pulp bleaching. The purified enzyme had a molecular weight of ~50
kDa with optimal activity at pH 9.0 and 50 degrees C. The enzyme showed good
activity retention (85%) after 2 h incubation at 50 degrees C and pH 9.0. This
enzyme obeyed Michaelis-Menten kinetics with regard to beechwood xylan with K m
and V max values of 5.6 mg/ml, 433 MUM/min/mg proteins, respectively. The enzyme
activity was stimulated by Mn2+, Ca2+ and Fe2+ metal ions. Further, it also
showed good tolerance to phenolics (2 mM) in the presence of syringic acid (no
loss), cinnamic acid (97%), benzoic acid (94%) and phenol (97%) activity
retention. The thermostability of xylanase was increased by 6.5-fold in presence
of sorbitol (0.75 M). Further, pulp treated with 20U/g of xylanase (20IU/g) alone
and with sorbitol (0.75M) reduced kappa number by 18.3 and 23.8%, respectively
after 3 h reaction. In summary, presence of xylanase shows good pulp-bleaching
activity, good tolerance to phenolics, lignin and metal ions and is amenable to
thermostability improvement by addition of polyols. The SEM image showed
significant changes on the surface of xylanase-treated pulp fiber as a result of
xylan hydrolysis.
PMID- 28401459
TI - Optimizing culture conditions for establishment of hairy root culture of
Semecarpus anacardium L.
AB - Semecarpus anacardium L. is a tree species which produces secondary metabolites
of medicinal importance. Roots of the plant have been traditionally used in folk
medicines. Different strains of Agrobacterium rhizogenes (A4, ATCC15834 and LBA
9402) were used for induction of hairy roots in in vitro grown tissues of the
plant. Hairy root initiation was observed after 25-30 days of infection. Optimum
transformation frequency of 61% was achieved on leaf explants with ATCC15834
strain. Infection time of 30 min resulted in greater transformation frequency
compared to 10 and 20 min, respectively. The hairy roots cultured in growth
regulator-free semi-solid woody plant medium differentiated into callus. Whole
shoots infected with ATCC 15834 were found to produce more transformants upon co
cultivation for 4 (65%) and 5 (67%) days. Induction of hairy roots in stem
explants infected with ATCC 15834 was lower (52%) compared to leaves (62%) after
4 days of co-cultivation. In A4 and LBA9402 strains transformation efficiency was
49 +/- 2.8% and 36 +/- 5.7% in shoots after 4 days of co-cultivation.
Transformation frequency was higher in ATCC15834 strain, irrespective of
explants. The hairy roots of S. anacardium elongated slowly upon transfer to half
strength liquid medium. After 3-4 passages in liquid medium slender hairy roots
started differentiating which were separated from the original explants. Visible
growth of the roots was observed in hormone-free liquid medium after 2-3 months
of culturing. Polymerase chain reaction with gene-specific primers from rol A, B
and C genes confirms the positive transformation events.
PMID- 28401460
TI - Enhanced production of berberine in In vitro regenerated cell of Tinospora
cordifolia and its analysis through LCMS QToF.
AB - Tinospora cordifolia is a prioritized medicinal plant and having an immense
medicinal importance especially in Indian medicinal system. But this plant needs
a regeneration protocol for its rapid propagation. An efficient regeneration
protocol was developed for T. cordifolia using nodal explants. High frequency of
multiple shoot formation was induced when the nodal segments were cultured on MS
medium supplemented with BAP (1.0 mg L-1) and 2-iP (0.5 mg L-1). The highest mean
number of shoots per nodal explant (7.9 +/- 0.45) with highest shoot length (9.3
+/- 0.48 cm) and 86% response were achieved on this media and hormonal
concentration. The optimum rooting was obtained on 1/2 strength of MS medium
augmented with IBA (0.5 mg L-1) with 8.3 +/- 0.46 cm root length and 89%
response. Micropropagated plantlets were found to be identical with the mother
plant when clonal fidelity of these plantlets were analyzed with inter simple
sequence repeat (ISSR) marker. The berberine content was analyzed through LCMS
QToF and the highest amount was found in in vitro callus (19.8 ug/gm) followed by
stem (9.3 ug/gm) and leaves of field-grown plants (8.4 ug/gm). Further, presence
of berberine was confirmed by ESI-MS spectra with protonated molecular ions ([M +
H]+) at m/z 336. Furthermore, MS-MS fragmentation pattern confirmed for the
presence of berberine in both the samples. Both the spectra (standard and
samples) showed common peaks for berberine in the form of protonated molecular
ions ([M + H]+) at m/z 320, m/z 304, m/z 292, m/z 278 in MS/MS mode. The study
revealed that developed protocol is potent for rapid mass propagation of this
plant species with high accumulation of important secondary metabolite berberine.
PMID- 28401461
TI - Continuous production of indole-3-acetic acid by immobilized cells of
Arthrobacter agilis.
AB - Indole acetic acid (IAA) is a plant growth-promoting hormone used in agriculture;
therefore, its continuous production is of paramount importance. IAA-producing
eight bacteria were isolated from the rhizosphere of Verbascum vulcanicum. Among
them, Arthrobacter agilis A17 gave maximum IAA production (75 mg/L) and this
strain was used to immobilization studies. The A. agilis A17 cells were
immobilized in calcium alginate for the production of IAA. Optimization of
process parameters for IAA production was carried out to enhance IAA production
using immobilized cells. The maximal production of IAA was 520 mg/L under the
following optimal conditions: 1% mannitol, 30 degrees C, pH 8.0, and 24 h
incubation. It was determined that the immobilized cells could be reused (13
times) for the production of IAA.
PMID- 28401462
TI - Purification and structural elucidation of three bioactive compounds isolated
from Streptomyces coelicoflavus BC 01 and their biological activity.
AB - The strain Streptomyces coelicoflavus BC 01 was isolated from mangrove soil and
used as inoculum for submerged fermentation. The fermented broth was extracted
with ethyl acetate, the crude extract was subjected to silica gel column
chromatography and the homogeneity of the isolated fractions was determined by
TLC and then subjected to RP-HPLC for their purity. The purification steps led to
the isolation of three pure bioactive compounds named as BC 01_C1, BC 01_C2 and
BC 01_C3. The chemical structure of these three compounds was established on the
basis of their spectroscopic studies like UV, IR, 1H and 13C NMR and GC-MS data
by comparison with reference data from literature. The structure of the compound
BC 01_C1 was established as 5-amino-2-(6-(2-hydroxyethyl)-3-oxononyl) cyclohex-2
enone. The compound BC 01_C2 was established as8-(aminomethyl)-7-hydroxy-1-(1
hydroxy-4-(hydroxylmethoxy)-2,3-dimethylbutyl)-2-methyl dodecahydro phenanthren
9(1H)-one and the compound BC 01_C3 was established as1-((E)-2-ethylhex-1-en-1
yl)2-((E)-2-ethylidenehexyl)cyclohexane-1,2-dicarboxylate. The MIC values of the
three isolated compounds (BC 01_C1, BC 01_C2 and BC 01_C3) were found between
12.5-75 MUg/ml for bacteria and 50-125 MUg/ml for fungi used in this study. These
compounds also possess in vitro antioxidant and anti-inflammatory activities.
PMID- 28401463
TI - Crop specific plant growth promoting effects of ACCd enzyme and siderophore
producing and cynogenic fluorescent Pseudomonas.
AB - Fluorescent Pseudomonas, aerobic, Gram-negative bacteria possess many traits that
make them well suited as biocontrol and growth promoting agents. Our study
revealed that isolates vary in mechanisms involved in the antagonist interactions
against pathogen and growth stimulatory effects on host plant. Most of the
potential antagonistic fluorescent Pseudomonas identified were avid iron
chelators (P233, P201, 176, P76 and, P76). Wide variation in ACCd enzyme
production was observed. ACCd enzyme assay tested P141 > P247 > P126, as
potential ACCd enzyme producer. Cynogenic fluorescent Pseudomonas isolates P76
and P124 exerted strong inhibitory against S. rolfsii. However, another cynogenic
fluorescent Pseudomonas P179 had no influence against R solani and S. rolfsii
which remains unexplained. Noticeable crop specific plant growth stimulation
exerted by different fluorescent Pseudomonas was observed on wheat (P124),
chickpea (P72), lathyrus (P85, P216), greengram (P11), blackgram (P99, P233);
bottlegourd (P248, P167); rice (P176, P247).
PMID- 28401464
TI - Efficient regeneration and improved sonication-assisted Agrobacterium
transformation (SAAT) method for Catharanthus roseus.
AB - Catharanthus roseus is an important medicinal plant known for its pharmacological
qualities such as antimicrobial, anticancerous, antifeedant, antisterility,
antidiabetic activities. More than 130 bioactive compounds like vinblastine,
vindoline and vincristine have been synthesized in this plant. Extensive studies
have been carried out for optimization regeneration and transformation protocols.
Most of the protocol described are laborious and time-consuming. Due to
sophisticated protocol of regeneration and genetic transformation, the production
of these bioactive molecules is less and not feasible to be commercialized
worldwide. Here we have optimized the efficient protocol for regeneration and
transformation to minimize the time scale and enhance the transformation
frequency through Agrobacterium and sonication-assisted transformation (SAAT)
method. In this study, hypocotyl explants responded best for maximal production
of transformed shoots. The callus percentage were recorded 52% with 1.0 mg L-1
(BAP) and 0.5 mg L-1 (NAA) while 80% shoot percentage obtained with 4.0 mg L-1
(BAP) and 0.05 mg L-1 (NAA). The microscopic studies revealed that the expression
of GFP was clearly localized in leaf tissue of the C. roseus after transformation
of pRepGFP0029 construct. Consequently, transformation efficiency was revealed on
the basis of GFP localization. The transformation efficiency of SAAT method was
6.0% comparable to 3.5% as conventional method. Further, PCR analysis confirmed
the integration of the nptII gene in the transformed plantlets of C. roseus.
PMID- 28401465
TI - Metabolism of pyrene through phthalic acid pathway by enriched bacterial
consortium composed of Pseudomonas, Burkholderia, and Rhodococcus (PBR).
AB - Polycyclic aromatic hydrocarbons (PAHs) are highly recalcitrant compounds due to
their high hydrophobicity and tendency to partition in organic phase of soils.
Pyrene is a high-molecular weight PAH, which has human health concerns. In the
present study, a bacterial consortium, PBR, was developed from a long-term
polluted site, viz., Amlakhadi, Ankleshwar, Gujarat, for effective degradation of
pyrene. The consortium effectively metabolized pyrene as a sole source of carbon
and energy. The consortium comprised three bacterial species, Pseudomonas sp.
ASDP1, Burkholderia sp. ASDP2, and Rhodococcus sp. ASDP3. The maximum growth rate
of consortium was 0.060/h and the maximum pyrene degradation rate was 16
mg/l/day. The organic and inorganic nutrients along with different surfactants
did not affect pyrene degradation, but degradation rate moderately increased in
the presence of sodium succinate. The significant characteristic of the
consortium was that it possessed an ability to degrade six other hydrocarbons,
both independently and simultaneously at 37 degrees C, in BHM (pH 7.0) under
shaking conditions (150 rpm) and it showed resistance towards mercury at 10 mM
concentration. Phthalic acid as one of the intermediates during pyrene
degradation was detected through high-performance liquid chromatography (HPLC).
The efficiency of consortium for pyrene degradation was validated in simulated
microcosms' study, which indicated that 99% of pyrene was metabolized by the
consortium under ambient conditions.
PMID- 28401466
TI - Antibacterial effects of Lactobacillus isolates of curd and human milk origin
against food-borne and human pathogens.
AB - This study was undertaken to assess the antibacterial efficacy of lactobacilli
isolated from curd and human milk samples. Identities of thirty-one different
lactobacilli (20 from curd and 11 from human milk) were confirmed by genus
specific PCR and 16S rRNA-based sequencing. These strains belonged to five
species, Lactobacillus casei, L. delbrueckii, L. fermentum, L. plantarum, and L.
pentosus. Antibacterial activities of cell-free supernatants (CFSs) of all the
Lactobacillus isolates were estimated through standard agar-well diffusion assay,
against commonly occurring food-borne and clinically important human pathogens.
None of the lactobacilli cell-free supernatant (CFS) exhibited inhibitory
activity against four pathogens, namely Staphylococcus aureus, Listeria
monocytogenes, Escherichia coli, and Klebsiella pneumoniae. Bacillus cereus,
Salmonella enterica serovar Typhi, and Shigella flexneri were moderately
inhibited by majority of CFSs, whereas, weak activity was observed against
Pseudomonas aeruginosa and Proteus mirabilis. CFS of some of the curd isolates
displayed antagonistic activity against Streptococcus mutans; however, human milk
lactobacilli did not displayed any inhibitory activity against them. As expected,
Nisin (Nisaplin(r)) showed inhibitory activity against Gram-positive, S. aureus,
B. cereus, and L. monocytogenes. Interestingly, few of the examined CFSs
exhibited inhibitory activities against both Gram-positive and Gram-negative
pathogens. Findings from this study support the possibility to explore the tested
lactobacilli and their CFSs as natural bio-preservatives, alone or in combination
with approved bacteriocins in food and pharma formulations after validating their
safety.
PMID- 28401467
TI - Response of extreme haloarchaeon Haloarcula argentinensis RR10 to simulated
microgravity in clinorotation.
AB - Gravity is the fundamental force that may have operated during the evolution of
life on Earth. It is thus important to understand as to what the effects of
gravity are on cellular life. The studies related to effect of microgravity on
cells may provide greater insights in understanding of how the physical force of
gravity shaped life on Earth. The present study focuses on a unique group of
organisms called the Haloarchaea, which are known for their extreme resistance to
survive in stress-induced environments. The aim of the present investigation was
to study the effect of simulated microgravity on physiological response of
extremely halophilic archaeon, Haloarcula argentinensis RR10, under slow
clinorotation. The growth kinetics of the archaeon in microgravity was studied
using the Baryani model and the viable and apoptotic cells were assessed using
propidium iodide fluorescent microscopic studies. The physiological mechanism of
adaptation was activation of 'salt-in' strategy by intracellular sequestration of
sodium ions as detected by EDAX. The organism upregulated the production of
ribosomal proteins in simulated microgravity as evidenced by Matrix-assisted
laser desorption ionization Time of flight-Mass Spectrophotometry. Simulated
microgravity altered the antibiotic susceptibility of the haloarchaeon and it
developed resistance to Augmentin, Norfloxacin, Tobramycin and Cefoperazone,
rendering it a multidrug resistant strain. The presence of antibiotic efflux pump
was detected in the haloarchaeon and it also enhanced production of protective
carotenoid pigment in simulated microgravity. The present study is presumably the
first report of physiological response of H. argentinensis RR10 in microgravity
simulated under slow clinorotation.
PMID- 28401468
TI - Morphological and molecular characterization of Fusarium spp. associated with
olive trees dieback in Tunisia.
AB - Dieback and wilting symptoms caused by complex soilborne fungi are nowadays the
most serious threatening disease affecting olive trees (Olea europaea) in Tunisia
and presumably in many Mediterranean basin countries. Fusarium is one of the
important phytopathogenic genera associated with dieback symptoms of olive trees.
The objective of the present study was to confirm the pathogenicity of Fusarium
spp. isolated from several olive-growing areas in Tunisia. According to the
pathogenic test done on young olive trees (cv. Chemlali), 23 out of 104 isolates
of Fusarium spp. were found to be pathogenic and the others were weakly or not
pathogenic. The pathogenic Fusarium spp. isolates were characterized using
molecular methods based on ITS PCR. Isolation results revealed the predominance
of Fusarium solani (56.5%) and F. oxysporum species (21.7%) compared to F.
chalmydosporum (8.7%), F. brachygibbosum (8.7%) and F. acuminatum (4.34%). Based
on pathogenicity test, disease severity was highly variable among the 23
pathogenic isolates tested (P < 0.05) where F. solani was the most aggressive
dieback agent. To the best of our knowledge, this is the first work that shows
that Fusarium spp. might be a major agent causing dieback disease of olive trees
in Tunisia.
PMID- 28401469
TI - Bioactive Amento flavone isolated from Cassia fistula L. leaves exhibits
therapeutic efficacy.
AB - Novel natural compounds endowed with sound bioactivities are currently the utmost
need as leads toward drug discovery. For the first time, here, we report the
presence of Amentoflavone (biflavonoid) in the leaves of Cassia fistula L.
Structural characterization was carried out using ultraviolet-visible
spectrophotometer, Fourier transform infrared, nuclear magnetic resonance, and
thin-layer chromatography. The isolated compound was further evaluated for its
bioactivity. The compound demonstrated moderate cytotoxicity in liver carcinoma
(HepG2) cells, and the comparative analysis for the standard and normal compound
has also been validated. Antioxidant potential was assessed by DPPH assay.
Furthermore, efficacy of the compound in the aforesaid assays asserts its
bioactivity and subsequently its importance as a potent therapeutic. Our study
strongly suggests that Amentoflavone present in the leaf extracts of C. fistula
L. definitely holds promise in the pharmaceutical industry.
PMID- 28401471
TI - Einthoven dissertation prizes 2016.
PMID- 28401470
TI - Streptomyces artemisiae MCCB 248 isolated from Arctic fjord sediments has unique
PKS and NRPS biosynthetic genes and produces potential new anticancer natural
products.
AB - After screening marine actinomycetes isolated from sediment samples collected
from the Arctic fjord Kongsfjorden for potential anticancer activity, an isolate
identified as Streptomyces artemisiae MCCB 248 exhibited promising results
against the NCI-H460 human lung cancer cell line. H460 cells treated with the
ethyl acetate extract of strain MCCB 248 and stained with Hoechst 33342 showed
clear signs of apoptosis, including shrinkage of the cell nucleus, DNA
fragmentation and chromatin condensation. Further to this treated cells showed
indications of early apoptotic cell death, including a significant proportion of
Annexin V positive staining and evidence of DNA damage as observed in the TUNEL
assay. Amplified PKS 1 and NRPS genes involved in secondary metabolite production
showed only 82% similarity to known biosynthetic genes of Streptomyces,
indicating the likely production of a novel secondary metabolite in this extract.
Additionally, chemical dereplication efforts using LC-MS/MS molecular networking
suggested the presence of a series of undescribed tetraene polyols. Taken
together, these results revealed that this Arctic S. artemisiae strain MCCB 248
is a promising candidate for natural products drug discovery and genome mining
for potential anticancer agents.
PMID- 28401472
TI - Dizziness and slow heart rate during exercise.
PMID- 28401473
TI - Dizziness and slow heart rate during exercise.
PMID- 28401474
TI - Tracking Effects of SIL1 Increase: Taking a Closer Look Beyond the Consequences
of Elevated Expression Level.
AB - SIL1 acts as a co-chaperone for the major ER-resident chaperone BiP and thus
plays a role in many BiP-dependent cellular functions such as protein-folding
control and unfolded protein response. Whereas the increase of BiP upon cellular
stress conditions is a well-known phenomenon, elevation of SIL1 under stress
conditions was thus far solely studied in yeast, and different studies indicated
an adverse effect of SIL1 increase. This is seemingly in contrast with the
beneficial effect of SIL1 increase in surviving neurons in neurodegenerative
disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. Here, we
addressed these controversial findings. Applying cell biological, morphological
and biochemical methods, we demonstrated that SIL1 increases in various mammalian
cells and neuronal tissues upon cellular stress. Investigation of heterozygous
SIL1 mutant cells and tissues supported this finding. Moreover, SIL1 protein was
found to be stabilized during ER stress. Increased SIL1 initiates ER stress in a
concentration-dependent manner which agrees with the described adverse SIL1
effect. However, our results also suggest that protective levels are achieved by
the secretion of excessive SIL1 and GRP170 and that moderately increased SIL1
also ameliorates cellular fitness under stress conditions. Our
immunoprecipitation results indicate that SIL1 might act in a BiP-independent
manner. Proteomic studies showed that SIL1 elevation alters the expression of
proteins including crucial players in neurodegeneration, especially in
Alzheimer's disease. This finding agrees with our observation of increased SIL1
immunoreactivity in surviving neurons of Alzheimer's disease autopsy cases and
supports the assumption that SIL1 plays a protective role in neurodegenerative
disorders.
PMID- 28401476
TI - Robotic Buccal Ureteroplasty: a Review of the Current Literature.
AB - PURPOSE OF REVIEW: This study aimed to provide an overview of the literature on
buccal mucosal ureteroplasty for ureteral stricture disease, with a specific
focus on the application of the robotic platform to buccal ureteroplasty. RECENT
FINDINGS: In our review, we highlight the results of Zhao et al. from the New
York University School of Medicine Department of Urology, as well as our own
results from Temple University Hospital. Zhao et al. published the first series
of four patients who underwent robotic buccal ureteroplasty. Mean stricture
length was 3.0 cm, and at a mean follow-up of 15 months, all repairs remained
patent. We also describe our results in 10 patients who underwent robotic buccal
ureteroplasty at Temple University Hospital. Median stricture length was 3.0 cm,
and at a median follow-up of 5 months, all repairs remain patent. Robotic buccal
ureteroplasty offers a promising option for repair of complex ureteral
strictures.
PMID- 28401477
TI - A Recombinant Probiotic, Lactobacillus casei, Expressing the Clostridium
perfringens alpha-toxoid, as an Orally Vaccine Candidate Against Gas Gangrene and
Necrotic Enteritis.
AB - The alpha-toxin is one of the virulence factors of Clostridium perfringens for
gas gangrene in humans and animals or necrotic enteritis in poultry. The C
terminal domain of this toxin ( cpa 247-370 ) was synthesized and cloned into
pT1NX vector to construct the pT1NX-alpha plasmid. This surface-expressing
plasmid was electroporated into Lactobacillus casei ATCC 393, generating the
recombinant L. casei strain expressing alpha-toxoid (LC-alpha strain). Expression
of this modified alpha-toxoid was confirmed by SDS-PAGE, immunoblotting, and
direct immunofluorescence microscopy. BALB/c mice, immunized orally by the
recombinant LC-alpha strain, elicited mucosal and significantly humoral immune
responses (p < 0.05) and developed a protection against 900 MLD/mL of the
standard alpha-toxin. This study showed that this recombinant LC-alpha strain
could be a promising vaccine candidate against gas gangrene and necrotic
enteritis.
PMID- 28401475
TI - Mitochondrial Quality Control and Disease: Insights into Ischemia-Reperfusion
Injury.
AB - Mitochondria are key regulators of cell fate during disease. They control cell
survival via the production of ATP that fuels cellular processes and, conversely,
cell death via the induction of apoptosis through release of pro-apoptotic
factors such as cytochrome C. Therefore, it is essential to have stringent
quality control mechanisms to ensure a healthy mitochondrial network. Quality
control mechanisms are largely regulated by mitochondrial dynamics and mitophagy.
The processes of mitochondrial fission (division) and fusion allow for damaged
mitochondria to be segregated and facilitate the equilibration of mitochondrial
components such as DNA, proteins, and metabolites. The process of mitophagy are
responsible for the degradation and recycling of damaged mitochondria. These
mitochondrial quality control mechanisms have been well studied in chronic and
acute pathologies such as Parkinson's disease, Alzheimer's disease, stroke, and
acute myocardial infarction, but less is known about how these two processes
interact and contribute to specific pathophysiologic states. To date, evidence
for the role of mitochondrial quality control in acute and chronic disease is
divergent and suggests that mitochondrial quality control processes can serve
both survival and death functions depending on the disease state. This review
aims to provide a synopsis of the molecular mechanisms involved in mitochondrial
quality control, to summarize our current understanding of the complex role that
mitochondrial quality control plays in the progression of acute vs chronic
diseases and, finally, to speculate on the possibility that targeted manipulation
of mitochondrial quality control mechanisms may be exploited for the rationale
design of novel therapeutic interventions.
PMID- 28401478
TI - Improved Detection of Norovirus and Hepatitis A Virus in Surface Water by
Applying Pre-PCR Processing.
AB - Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) detection
of waterborne RNA viruses generally requires concentration of large water volumes
due to low virus levels. A common approach is to use dead-end ultrafiltration
followed by precipitation with polyethylene glycol. However, this procedure often
leads to the co-concentration of PCR inhibitors that impairs the limit of
detection and causes false-negative results. Here, we applied the concept of pre
PCR processing to optimize RT-qPCR detection of norovirus genogroup I (GI),
genogroup II (GII), and hepatitis A virus (HAV) in challenging water matrices.
The RT-qPCR assay was improved by screening for an inhibitor-tolerant master mix
and modifying the primers with twisted intercalating nucleic acid molecules.
Additionally, a modified protocol based on chaotropic lysis buffer and magnetic
silica bead nucleic acid extraction was developed for complex water matrices. A
validation of the modified extraction protocol on surface and drinking waters was
performed. At least a 26-fold improvement was seen in the most complex surface
water studied. The modified protocol resulted in average recoveries of 33, 13, 8,
and 4% for mengovirus, norovirus GI, GII, and HAV, respectively. The modified
protocol also improved the limit of detection for norovirus GI and HAV. RT-qPCR
inhibition with C q shifts of 1.6, 2.8, and 3.5 for norovirus GI, GII, and HAV,
respectively, obtained for the standard nucleic acid extraction were completely
eliminated by the modified protocol. The standard nucleic acid extraction method
worked well on drinking water with no RT-qPCR inhibition observed and average
recoveries of 80, 124, 89, and 32% for mengovirus, norovirus GI, GII, and HAV,
respectively.
PMID- 28401480
TI - Target-Mediated Drug Disposition Pharmacokinetic-Pharmacodynamic Model of
Bosentan and Endothelin-1.
AB - BACKGROUND AND OBJECTIVES: Bosentan is a competitive antagonist on endothelin
receptor A and B (ETA and ETB), displacing the endogenous binding partner
endothelin-1 (ET-1) from its binding sites. After administration of escalating
single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan showed dose
dependent pharmacokinetics (PK). The aim of this analysis was to develop a PK
model of bosentan after i.v. administration including competitive antagonism with
ET-1 and to analyze its influence on blood pressure and heart rate with a
combined pharmacokinetic/pharmacodynamic (PK/PD) model. METHODS: PK/PD data from
70 young male Caucasian subjects were analyzed after single i.v. administration
of 10, 50, 250, 500, and 750 mg of bosentan. Population analyses, simulations,
and evaluation were performed using a non-linear mixed-effects modeling approach.
RESULTS: The PK of bosentan was best described by a two-compartment, target
mediated drug disposition (TMDD) model. ET-1 plasma and urine profiles were
successfully integrated into the bosentan two-compartment, TMDD model
encompassing competition for the same receptor. A multiple-peak phenomenon of
bosentan plasma concentrations after i.v. administration was best described by a
diurnal expression or reappearance of ET receptors on the cell surface. Blood
pressure was best described by an E max model; heart rate was modeled as a
compensatory effect of changes in blood pressure. CONCLUSION: The developed
competitive PK/PD model of bosentan and ET-1 after i.v. administration provides a
first step towards understanding the complex PK properties of bosentan and offers
a valuable tool for future PK/PD research.
PMID- 28401482
TI - Attractiveness of Different Food Resources to Dung Beetles (Coleoptera:
Scarabaeidae) of a Dry Tropical Area.
AB - Excrement scarcity is one of the main historical factors leading dung beetles to
adapt to other food resources. In the Caatinga, a seasonally tropical dry forest,
harsh environmental conditions seem to restrict the availability of food
resources. In this scenario, the aim of our study was to experimentally
investigate the attractiveness of different potential food resources to these
insects in the Caatinga. Field samplings were performed, and we tested five
resources in pitfall baited traps: excrement, carrion, fruits of two species of
columnar cacti, and seeds of one species of Euphorbiaceae (Jatropha mollissima
(Pohl)). In a controlled setting, we tested dietary preferences of Deltochilum
verruciferum Felsche by offering one or two resources simultaneously. In the
field experiments, 297 dung beetles (9 species) were recovered from the traps,
and D. verruciferum was the most abundant species. Carrion and excrement were the
most attractive resources. Controlled dietary preference tests with D.
verruciferum evidenced that these beetles used all tested food resources,
excrement and carrion most pronouncedly. Our findings support copro-necrophagy as
the main feeding habit of D. verruciferum, but also suggest that alternative
resources might be utilized if preferred resources are scarce.
PMID- 28401481
TI - Why is Aedes aegypti Linnaeus so Successful as a Species?
AB - Diseases transmitted by mosquitoes impose enormous burden towards human morbidity
and mortality. Over the last three decades, Brazil has suffered from severe
Dengue epidemics. In September 2014, this situation is further complicated by the
introduction of two other viruses, Zika and Chikungunya, placing Brazil in a
triple epidemic. In this article, we discuss the biology of Aedes aegypti
Linnaeus, and the principal initiatives currently used to control mosquito
populations and the diseases they transmit. Aedes aegypti has broad global
distribution and is involved in the transmission of various arboviral diseases
such as Dengue, Zika, and Chikungunya. Several factors contribute to the success
of the species, particularly behavioral plasticity, rapid development,
desiccation-resistant eggs, resistance to the principle insecticide classes
currently available on the market, preference for the urban environment, and
proximity to humans. Vector control programs are the best way to reduce the
burden of mosquito-borne diseases. Chemical control is most commonly used in
recent times, and unfortunately, the results have not been satisfactory but
instead, there is increased vector dispersal and, subsequently, the spread of
disease epidemics. Investigations of alternative control methods such as release
of Wolbachia-infected mosquitoes for blocking vector-borne pathogens, release of
transgenic mosquitoes carrying a lethal gene for offspring, and the use of
insecticide-dispersing mosquitoes are under way in Brazil, and some have shown
promising results. Special emphasis should be placed on integrated management of
all available tactics, so as to maximize efforts towards mosquito control.
Finally, we emphasize that continuous actions and community participation control
initiatives are critically important for success.
PMID- 28401483
TI - Molecular profiling of gene copy number abnormalities in key regulatory genes in
high-risk B-lineage acute lymphoblastic leukemia: frequency and their association
with clinicopathological findings in Indian patients.
AB - Genes related to key cellular pathways are frequently altered in B cell ALL and
are associated with poor survival especially in high-risk (HR) subgroups. We
examined gene copy number abnormalities (CNA) in 101 Indian HR B cell ALL
patients and their correlation with clinicopathological features by multiplex
ligation-dependent probe amplification. Overall, CNA were detected in 59 (59%)
cases, with 26, 10 and 23% of cases harboring 1, 2 or +3 CNA. CNA were more
prevalent in BCR-ABL1 (60%), pediatric (64%) and high WCC (WBC count) (63%)
patients. Frequent genes deletions included CDNK2A/B (26%), IKZF1 (25%), PAX5
(14%), JAK2 (7%), BTG1 (6%), RB1 (5%), EBF1 (4%), ETV6 (4%), while PAR1 region
genes were predominantly duplicated (20%). EBF1 deletions selectively associated
with adults, IKZF1 deletions occurred frequently in high WCC and BCR-ABL1 cases,
while PAR1 region gains significantly associated with MLL-AF4 cases. IKZF1
haploinsufficiency group was predominant, especially in adults (65%), high WCC
(60%) patients and BCR-ABL1-negative (78%) patients. Most cases harbored multiple
concurrent CNA, with IKZF1 concomitantly occurring with CDNK2A/B, PAX5 and BTG1,
while JAK2 occurred with CDNK2A/B and PAX5. Mutually exclusive CNA included ETV6
and IKZF1/RB1, and EBF1 and JAK2. Our results corroborate with global reports,
aggregating molecular markers in Indian HR B-ALL cases. Integration of CNA data
from rapid methods like MLPA, onto background of existing gold-standard methods
detecting significant chromosomal abnormalities, provides a comprehensive genetic
profile in B-ALL.
PMID- 28401484
TI - Vascular microinvasion from hepatocellular carcinoma: CT findings and pathologic
correlation for the best therapeutic strategies.
AB - Recurrence of HCC reduces survival rates in patients treated with surgery, and
one of the most relevant risk factors for tumour recurrence is microvascular
invasion (mVI). The identification of mVI on preoperative examinations could
improve surgical planning's and techniques so as to reduce the risk of tumour
recurrence. During our study, we have revised 101 CT examinations of the liver
performed on patients diagnosed with solitary HCC who had surgical treatment and
pathological analysis of the specimens for mVI in order to detect CT signs which
could be reliable in mVI prediction. On CT examinations, the tumours were
evaluated for margins, capsule, size, contrast enhancement, halo sign and Thad.
From our statistical analysis, we found out that irregularity in tumour margins
and defects in peritumoural capsule are the most significant characteristics
predicting mVI in HCC. Every report on CT examinations performed on surgical
candidate patients should include suggestions about mVI probability in order to
tailor procedures, reduce tumour recurrence risk and improve survival rates.
PMID- 28401479
TI - Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant
Women: An Extended Repository of Model Parameters for Physiologically Based
Pharmacokinetic Modeling in Pregnancy.
AB - BACKGROUND: In the past years, several repositories for anatomical and
physiological parameters required for physiologically based pharmacokinetic
modeling in pregnant women have been published. While providing a good basis,
some important aspects can be further detailed. For example, they did not account
for the variability associated with parameters or were lacking key parameters
necessary for developing more detailed mechanistic pregnancy physiologically
based pharmacokinetic models, such as the composition of pregnancy-specific
tissues. OBJECTIVES: The aim of this meta-analysis was to provide an updated and
extended database of anatomical and physiological parameters in healthy pregnant
women that also accounts for changes in the variability of a parameter throughout
gestation and for the composition of pregnancy-specific tissues. METHODS: A
systematic literature search was carried out to collect study data on pregnancy
related changes of anatomical and physiological parameters. For each parameter, a
set of mathematical functions was fitted to the data and to the standard
deviation observed among the data. The best performing functions were selected
based on numerical and visual diagnostics as well as based on physiological
plausibility. RESULTS: The literature search yielded 473 studies, 302 of which
met the criteria to be further analyzed and compiled in a database. In total, the
database encompassed 7729 data. Although the availability of quantitative data
for some parameters remained limited, mathematical functions could be generated
for many important parameters. Gaps were filled based on qualitative knowledge
and based on physiologically plausible assumptions. CONCLUSION: The presented
results facilitate the integration of pregnancy-dependent changes in anatomy and
physiology into mechanistic population physiologically based pharmacokinetic
models. Such models can ultimately provide a valuable tool to investigate the
pharmacokinetics during pregnancy in silico and support informed decision making
regarding optimal dosing regimens in this vulnerable special population.
PMID- 28401485
TI - Silymarin and its active component silibinin act as novel therapeutic
alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling
cascade.
AB - PURPOSE: Approximately 20% of all salivary gland cancer patients who are treated
with current treatment modalities will ultimately develop metastases. Its most
common form, mucoepidermoid carcinoma (MEC) is a highly aggressive tumor with an
overall 5-year survival rate of ~30%. Until now, several chemotherapeutic drugs
have been tested for the treatment of salivary gland tumors, but the results have
been disappointing and the drugs often cause unwanted side effects. Therefore,
several recent studies have focused on the potential of alternative and/or
complementary therapeutic options, including the use of silymarin. METHODS: The
effects of silymarin and its active component silibinin on salivary gland cancer
derived MC3 and HN22 cells and their underlying molecular mechanisms were
examined using trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI)
staining, Live/Dead, Annexin V/PI staining, mitochondrial membrane potential
(DeltaPsim) measurement, quantitative RT-PCR, soft agar colony formation and
Western blotting analyses. RESULTS: We found that silymarin and silibinin
dramatically increased the expression of the pro-apoptotic protein Bim in a
concentration- and time-dependent manner and, concomitantly, induced apoptosis in
MC3 and HN22 cells. We also found that ERK1/2 signaling inhibition successfully
sensitized these cells to the apoptotic effects of silymarin and silibinin, which
indicates that the ERK1/2 signaling pathway may act as an upstream regulator that
modulates the silymarin/silibinin-induced Bim signaling pathway. CONCLUSIONS:
Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin
and silibinin increases the expression of the pro-apoptotic Bcl-2 family member
Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary
gland cancer-derived cells.
PMID- 28401486
TI - Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth,
migration and glial-to-mesenchymal transition.
AB - PURPOSE: Glioblastomas (GBM) comprise 17% of all primary brain tumors. These
tumors are extremely aggressive due to their infiltrative capacity and
chemoresistance, with glial-to-mesenchymal transition (GMT) proteins playing a
prominent role in tumor invasion. One compound that has recently been used to
reduce the expression of these proteins is shikonin (SHK), a naphthoquinone with
anti-tumor properties. Temozolomide (TMZ), the most commonly used
chemotherapeutic agent in GBM treatment, has so far not been studied in
combination with SHK. Here, we investigated the combined effects of these two
drugs on the proliferation and motility of GBM-derived cells. METHODS: The
cytotoxic and proliferative effects of SHK and TMZ on human GBM-derived cells
were tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
(MTT), Ki67 staining and BrdU incorporation assays. The migration capacities of
these cells were evaluated using a scratch wound assay. The expression levels of
beta3 integrin, metalloproteinases (MMPs) and GMT-associated proteins were
determined by Western blotting and immunocytochemistry. RESULTS: We found that
GBM-derived cells treated with a combination of SHK and TMZ showed decreases in
their proliferation and migration capacities. These decreases were followed by
the suppression of GMT through a reduction of beta3 integrin, MMP-2, MMP-9, Slug
and vimentin expression via inactivation of PI3K/AKT signaling. CONCLUSION: From
our results we conclude that dual treatment with SHK and TMZ may constitute a
powerful new tool for GBM treatment by reducing therapy resistance and tumor
recurrence.
PMID- 28401487
TI - Perception in attention deficit hyperactivity disorder.
AB - A large body of research demonstrated that individuals with attention deficit
hyperactivity disorder (ADHD) suffer from various neuropsychological deficits. In
contrast, less is known and only divergent evidence exists on perceptual
functions of individuals with ADHD. This is problematic as neuropsychological and
perceptual functions are closely interrelated and are often difficult to
disentangle in behavioral assessments. This study presents the conduct and
results of a systematic literature review on perceptual functions in children and
adults with ADHD. This review considers studies using psychophysical methods
(objective measurements) and self- and informant reports (subjective
measurements). Results indicate that individuals with ADHD have altered
perceptual functions in various domains as compared to typically developing
individuals. Increased perceptual functions in individuals with ADHD were found
with regard to olfactory detection thresholds, whereas reduced perceptual
functions were evident for aspects of visual and speech perception. Moreover,
individuals with ADHD were found to experience discomfort to sensory stimuli at a
lower level than typically developing individuals. Alterations of perceptual
functions in individuals with ADHD were shown to be moderated by various factors,
such as pharmacological treatment, cognitive functions, and symptom severity. We
conclude by giving implications for daily life functioning and clinical practice.
PMID- 28401488
TI - A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and
oligozoospermia in a consanguineous Turkish family.
AB - PURPOSE: The purpose of this study was to identify mutations that cause non
syndromic male infertility using whole exome sequencing of family cases. METHODS:
We recruited a consanguineous Turkish family comprising nine siblings with male
triplets; two of the triplets were infertile as well as one younger infertile
brother. Whole exome sequencing (WES) performed on two azoospermic brothers
identified a mutation in the melanoma antigen family B4 (MAGEB4) gene which was
confirmed via Sanger sequencing and then screened for on control groups and
unrelated infertile subjects. The effect of the mutation on messenger RNA (mRNA)
and protein levels was tested after in vitro cell transfection. Structural
features of MAGEB4 were predicted throughout the conserved MAGE domain. RESULTS:
The novel single-base substitution (c.1041A>T) in the X-linked MAGEB4 gene was
identified as a no-stop mutation. The mutation is predicted to add 24 amino acids
to the C-terminus of MAGEB4. Our functional studies were unable to detect any
effect either on mRNA stability, intracellular localization of the protein, or
the ability to homodimerize/heterodimerize with other MAGE proteins. We thus
hypothesize that these additional amino acids may affect the proper protein
interactions with MAGEB4 partners. CONCLUSION: The whole exome analysis of a
consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of
inherited male infertility. This study provides the first clue to the
physiological function of a MAGE protein.
PMID- 28401489
TI - Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice.
AB - Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10
in the dorsal root ganglion mediate itch in experimental allergic contact
dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of
neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic
itch remains unclear. Here, we report that Cxcr3 -/- mice showed normal
scratching in acute itch models but reduced scratching in chronic itch models of
dry skin and ACD. In contrast, both formalin-induced acute pain and complete
Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 -/-
mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal
cord in the dry skin model induced by acetone and diethyl ether followed by water
(AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch.
Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW
treatment was suppressed in Cxcr3 -/- mice. Finally, AEW-induced astrocyte
activation was inhibited in Cxcr3 -/- mice. Taken together, these data suggest
that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may
provide effective treatment for chronic pruritus.
PMID- 28401490
TI - The Report Card on BMI Report Cards.
AB - PURPOSE OF REVIEW: Half of states in the USA have legislation requiring that
schools conduct body mass index (BMI) screening among students; just under half
of these states report results to parents. The effectiveness of school-based BMI
screening and reporting in reducing childhood obesity is not established and the
practice has raised concerns about the potential for increased weight-based
stigmatization. RECENT FINDINGS: Recent experimental studies of BMI screening and
reporting have not demonstrated a positive impact on students' weight status.
However, the language and formatting of BMI reports used in studies to date have
been suboptimal and have likely limited the potential effectiveness of the
practice. This article reviews the recent literature on school-based BMI
screening and reporting and highlights important areas for future inquiry. The
present review suggests that evidence to date is not sufficient to support
definitive conclusions about the value of school-based BMI screening and
reporting as a childhood obesity prevention tool.
PMID- 28401491
TI - Faith-Based Institutions as Venues for Obesity Prevention.
AB - PURPOSE OF REVIEW: The aim of this current narrative review is to critique the
scope and value of recent studies with a focus on obesity-related health
promotion in faith organizations. RECENT FINDINGS: Electronic database searches,
scanning of the reference lists of identified articles, and hand searching of
journals for articles written in English and published in 2013-2016 revealed 16
studies. Half of the studies involved African-Americans, in churches and with
predominantly female participants. Research among other ethnic groups was more
likely to be exploratory. All of the 11 studies reporting the impact of
programmes on weight-related measures showed favourable outcomes. However, due to
study limitations (small sample size, short duration, attrition), significant
unbiased effects cannot yet be concluded for most of the interventions reviewed.
Study strengths included application of theory in community engagement and
detailed description of cultural tailoring. Faith organizations show promise as
settings for obesity prevention among high-risk groups, particularly African
Americans. Support for progressing formative work to adequately powered,
randomized controlled trials is vital. Wider involvement of diverse faith
settings and targeting obesity in men and childhood would be valuable
developments.
PMID- 28401493
TI - Characterization of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Among
Patients Admitted to Kenyatta National Hospital: A Retrospective Cross-Sectional
Study.
AB - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
are severe cutaneous reactions. There is scant literature on the characteristics
and causes of these conditions in Kenyatta National Hospital. OBJECTIVE: The aim
of this study was to determine the prevalence, risk factors, and etiologies of
SJS/TEN among patients admitted to Kenyatta National Hospital. METHODS: A
retrospective cross-sectional study was done to find the characteristics and
causes of severe cutaneous reactions among patients admitted to Kenyatta National
Hospital. Universal sampling was employed, whereby all 115 patients with severe
cutaneous reactions between June 2006 and June 2016 were studied. Information
collected included participants' sociodemographic variables, clinical
characteristics of the disease, and the possible triggers. Data were analyzed
using STATA version 13 at p <= 0.05. RESULTS: The mean age of patients was 31
years (+/-20). Low case numbers precluded statistically significant results;
however, females represented 59.1% of patients, and 46.1% of patients were
diagnosed between the ages of 21 and 40 years. SJS occurred in 47% of patients
followed by TEN in 33.9% and SJS/TEN overlap in 19.1%. Drugs were determined to
be the causative agent in 94.8% of the severe cutaneous reactions followed by
infectious agents at 5.2%, principally HIV, herpes simplex virus 1, and
mycoplasma. The most common drugs implicated were sulfonamides (26.1%) and
nevirapine (15.7%). CONCLUSION: Numerically, SJS was the most common subtype of
SJS/TEN in Kenyatta National Hospital and was usually attributed to use of drugs,
especially sulfonamides. Severe cutaneous reactions were observed more frequently
in females and in patients aged between 21 and 40 years, indicating that
emphasizing surveillance and medication counselling in these patient populations
could be beneficial.
PMID- 28401492
TI - The Alphabet Soup of HIV Reservoir Markers.
AB - PURPOSE OF REVIEW: Despite the success of antiretroviral therapy in suppressing
HIV, life-long therapy is required to avoid HIV reactivation from long-lived
viral reservoirs. Currently, there is intense interest in searching for
therapeutic interventions that can purge the viral reservoir to achieve complete
remission in HIV patients off antiretroviral therapy. The evaluation of such
interventions relies on our ability to accurately and precisely measure the true
size of the viral reservoir. In this review, we assess the most commonly used HIV
reservoir assays, as a clear understanding of the strengths and weaknesses of
each is vital for the accurate interpretation of results and for the development
of improved assays. RECENT FINDINGS: The quantification of intracellular or
plasma HIV RNA or DNA levels remains the most commonly used tests for the
characterization of the viral reservoir. While cost-effective and high
throughput, these assays are not able to differentiate between replication
competent or defective fractions or quantify the number of infected cells. Viral
outgrowth assays provide a lower bound for the fraction of cells that can produce
infectious virus, but these assays are laborious, expensive and substantially
underestimate the potential reservoir of replication-competent provirus. Newer
assays are now available that seek to overcome some of these problems, including
full-length proviral sequencing, inducible HIV RNA assays, ultrasensitive p24
assays and murine adoptive transfer techniques. The development and evaluation of
strategies for HIV remission rely upon our ability to accurately and precisely
quantify the size of the remaining viral reservoir. At this time, all current HIV
reservoir assays have drawbacks such that combinations of assays are generally
needed to gain a more comprehensive view of the viral reservoir. The development
of novel, rapid, high-throughput assays that can sensitively quantify the levels
of the replication-competent HIV reservoir is still needed.
PMID- 28401494
TI - A Comparative Optical Coherence Tomography Study of Spinocerebellar Ataxia Types
3 and 10.
AB - SCA3 presents with a CAG expansion at 14q24.3-q32 while SCA10 shows an ATTCT
expansion at 22q13-qter. SCA10 seems to be less aggressive than SCA3. For an in
vivo, noninvasive approach of the correlation between central nervous system and
clinical evolution, we can use optic coherence tomography (OCT) to measure
retinal nerve fiber (RNFL) and ganglion cell layer (GCL) thickness. To describe
OCT findings in SCA10, correlate it with expansion size and disease severity and
compare with those of SCA3. We analyzed ten individuals with SCA3 and nine with
SCA10 recruited from the neurology service of Hospital de Clinicas of Parana
Brazil. They were submitted to OCT and clinical evaluation using SARA score.
Expansion size, demographic data, time from disease onset, and age of onset were
collected. We found no correlation between size of expansion, SARA, and RNFL or
GCL thickness in SCA10. RNFL seemed to be thicker in SCA10 (p > 0.05). GCL
thickness, SARA, median age, and time from disease onset did not differ between
groups. SCA10 individuals had an earlier disease onset. In SCA3, there was a
negative correlation between SARA and RNFL thickness in nasal area. To the best
of our knowledge, this is the first paper assessing retinal changes by OCT in
individuals with SCA10. The lack of correlation between disease progression, age,
and time since onset supports the anatomopathological findings which suggest
SCA10 is less aggressive than other SCAs. The findings in SCA3 are in accordance
with the literature.
PMID- 28401495
TI - Cessation rate of anti-osteoporosis treatments and risk factors in Spanish
primary care settings: a population-based cohort analysis.
AB - : Among 95,057 patients >=50 years with new anti-osteoporosis medications (AOM)
(2001-2013) in primary care, 1-year cessation was 51% (28%-68%), higher in men,
smokers, patients with missing lifestyle data, and out normal BMI, and lower in
those aged 60-79, with recent fractures or other anti-osteoporotics, suggesting
non-severe osteoporosis and less risk awareness. PURPOSE: Low compliance to anti
osteoporosis medications (AOM) has been previously reported. We aimed to estimate
1-year cessation rates of different AOMs as used in Spanish healthcare settings,
and to identify associated risk factors. METHODS: A cohort study was performed
using primary care records data (BIFAP). Patients entered the cohort when aged 50
years in 2001-2013, with >=1 year of data available, and identified as incident
users of AOM (1-year washout). Participants were divided into six cohorts:
alendronate, other oral bisphosphonates, selective oestrogen receptor modulators,
strontium ranelate, teriparatide, and denosumab. Patients were followed from
therapy initiation to the earliest of cessation (90-day refill gap), switching
(to alternative AOM), loss to follow-up, death, or end of 2013. One-year therapy
cessation was estimated using life tables. Hazard ratios (of cessation) according
to age, sex, lifestyle factors, morbidity, and co-medication were estimated after
stepwise backwards selection. RESULTS: A total of 95,057 AOM users were
identified (91% women; mean age 68). One-year cessation was 51% overall, highest
for strontium ranelate (68%), and lowest for denosumab (28%). Cessation
probability was higher in men (14% to 2.1-fold), smokers (>6%), and patients with
missing BMI (19-28%) or smoking (6-20%) data, and overweight/obese/underweight
(7% to 2.6-fold increase compared to normal weight). Patients aged 60-79 years,
with a recent fracture or other drugs used for osteoporosis, had better
persistence. CONCLUSIONS: Over half of the patients initiating AOM stopped
therapy within the first year after initiation. The described risk factors for
cessation could be proxies for non-severe osteoporosis, and/or disease/risk
awareness, which could inform the targeting of high-risk patients for monitoring
and/or interventions aimed at improving persistence.
PMID- 28401496
TI - Calcium intake, bone mineral density, and fragility fractures: evidence from an
Italian outpatient population.
AB - : This study was performed in 1000 adult Italian subjects to focus on the effects
of dietary calcium intake on bone health. A higher fracture risk appears to be
associated with a reduced calcium intake. An adequate daily calcium intake is
recommended to counteract osteoporotic fractures. PURPOSE: The principal aim of
the present study was to focus on the effects of dietary calcium intake on bone
mineral density (BMD) and fragility fractures in a representative sample of an
adult Italian outpatient population. METHODS: The study group consisted of 1000
consecutive adult Italian subjects [838 women (F) and 162 men (M)] referred to
the Bone Metabolic Diseases Unit for the evaluation of their bone metabolism.
Daily dietary calcium intake was assessed using a specific food frequency
questionnaire (FFQ). Other evaluations included fracture risk, lumbar and femoral
BMD, heel ultrasound, fragility fractures, plasma concentration of parathyroid
hormone ([PTH]) and 25-hydroxy-vitamin D ([25(OH)D]), and urinary calcium.
RESULTS: Only 10.4% of the subjects (n = 104; 71 F and 33 M) had a daily calcium
intake adequate for adults (>=1000 mg/day). No correlation was found between
calcium intake and BMD. The transition from a daily dietary calcium intake <400
mg/day to a daily dietary calcium intake >=400 mg/day was associated with a
reduced fracture probability ratio at any site [from 42 to 21% (p < 0.05)].
Subjects with one or more vertebral fractures had a significantly lower dietary
calcium intake (<400 mg/day) than did subjects without vertebral fractures, and
they practiced physical activity only occasionally (p = 0.030). CONCLUSIONS:
Daily dietary calcium intake is lower than the recommended daily intake in an
Italian ambulatory population, and a higher fracture risk appears to be
associated with a reduced calcium intake. An age-adequate daily calcium intake,
combined with regular physical activity, is strongly recommended in order to
counteract fragility fractures.
PMID- 28401497
TI - Bortezomib combined with standard induction chemotherapy in Japanese children
with refractory acute lymphoblastic leukemia.
AB - Bortezomib has been shown to be effective and well-tolerated in patients with
refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in
Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not
been evaluated in Japanese pediatric patients. Here, we report the results of a
clinical trial designed to evaluate the safety of bortezomib combined with
induction chemotherapy in Japanese children with refractory ALL. A total of six
patients with B-precursor ALL were enrolled in this study. Four-dose bortezomib
(1.3 mg/m2/dose) combined with two standard induction chemotherapies was used.
Prolonged pancytopenia (grade 4) was observed in all patients. Four of the six
patients developed severe infectious complications. Peripheral neuropathy (grade
2) occurred in five patients. The individual plasma bortezomib concentration-time
profiles were not related to toxicity and efficacy. Five patients were evaluable
for response, and four patients achieved complete response (CR) or CR without
platelet recovery (80%). In conclusion, four-dose bortezomib (1.3 mg/m2/dose)
combined with standard re-induction chemotherapy was associated with a high risk
of infectious complications induced by prolonged neutropenia, although high
efficacy has been achieved for Japanese pediatric patients with refractory ALL.
Attention must be given to severe infectious complications when performing re
induction chemotherapy including bortezomib.
PMID- 28401499
TI - Clinical patterns of primary stabbing headache: a single clinic-based prospective
study.
AB - BACKGROUND: The clinical features and disease courses of primary stabbing
headache (PSH) are diverse. We aimed to identify distinct clinical patterns of
PSH. METHODS: We prospectively screened consecutive first-visit patients who
presented with stabbing headache at the Samsung Medical Centre Headache Clinic
from June 2015 to March 2016. Demographics, headache characteristics, and disease
courses were prospectively evaluated. After discerning factors related to the
chronicity at the time of presentation, clinical patterns were identified based
on the frequency (daily vs. intermittent), clinical course (remitted or not), and
total disease duration (<3 or >3 months). RESULTS: In the 65 patients with PSH
included in this study, monophasic (n = 31), intermittent (n = 17), and chronic
daily (n = 12) patterns were identified. The median disease durations were 9 days
for monophasic PSH, 9 months for chronic daily PSH, and 2 years for intermittent
PSH. The features of monophasic PSH were greater severity, single and side-locked
locations, more attacks per day, daily occurrence, and good treatment response.
Chronic daily PSH was associated with female predominance, longer-lasting stabs,
and multiple or migrating locations on bilateral or alternating sides. The
characteristics of intermittent PSH included female predominance and sporadic
stabs with less intensity. CONCLUSIONS: Our study demonstrated distinct clinical
patterns of PSH. In addition to help early recognition of disease, our findings
suggest different pathophysiologic mechanisms. Future prospective studies are
required to reveal the etiologies of these different PSH patterns and their
optimal treatment strategies.
PMID- 28401500
TI - Back to School: Racial and Gender Differences in Adults' Participation in Formal
Schooling, 1978-2013.
AB - Trends and gaps in educational attainment by race and gender have received much
attention in recent years, but reports of these trends have generally focused on
traditional-age college students. Little is known about whether and how
enrollment in formal schooling among older adults (between 29 and 61 years old)
has changed over time. In this article, I draw on Current Population Survey data
from 1978 to 2013 to provide the most comprehensive analysis of trends in adults'
formal school enrollment by demographic group to date. Results indicate that
adult black women in particular have seen relatively high growth rates in their
enrollment. Black women were 85 % more likely to enroll in 2011 and 46 % more
likely in 2013 than they were in 1978. Their growing advantage relative to other
racial-gender groups owes largely to their increasing educational attainment
rates overall, given the relationship between prior schooling and enrollment
later in life. Taken together, this article's findings suggest that adult
enrollment is at once equalizing and disequalizing. On the one hand, it has the
potential to narrow the gaps between those with some college experience and those
with a four-year degree. On the other hand, patterns of adults' participation in
formal education are widening educational gaps between those with and without
traditional-age college experience.
PMID- 28401498
TI - Identification of subgroups of patients with tension type headache with higher
widespread pressure pain hyperalgesia.
AB - BACKGROUND: Identification of subgroups of patients with different levels of
sensitization and clinical features can help to identify groups at risk and the
development of better therapeutic strategies. The aim of this study was to
identify subgroups of patients with tension type headache (TTH) with different
levels of sensitization, clinical pain features, and psychological outcomes.
METHODS: A total of 197 individuals with TTH participated. Headache intensity,
frequency, and duration and medication intake were collected with a 4-weeks
diary. Pressure pain thresholds were assessed bilaterally over the temporalis
muscle, C5-C6 joint, second metacarpal and tibialis anterior muscle to determine
widespread pressure pain hyperalgesia. The Hospital Anxiety and Depression Scale
assessed anxiety and depression. The State-Trait Anxiety Inventory evaluated the
state and trait levels of anxiety. The Headache Disability Inventory evaluated
the burden of headache. Health-related quality of life was determined with the SF
36 questionnaire. Groups were considered as positive (three or more criteria) or
negative (less than three criteria) on a clinical prediction rule: headache
duration <8.5 h/day; headache frequency <5.5 days/week; bodily pain <47 and
vitality <47.5. RESULTS: The ANCOVA revealed that subjects in group 1 (positive
rule, n = 89) exhibited longer headache history, shorter headache duration, lower
headache frequency, higher widespread pressure hyperalgesia, higher anxiety trait
levels, and lower quality of life (all, P < 0.01) than those subjects within
group 2 (negative rule, n = 108). Differences were similar between men and women.
CONCLUSIONS: This study identified a subgroup of patients with TTH with higher
sensitization, higher chronicity of headaches and worse quality of life but lower
frequency and duration of headache episodes. This subgroup of individuals with
TTH may need particular attention and specific therapeutic programs for avoiding
potential chronification.
PMID- 28401501
TI - The Sibsize Revolution and Social Disparities in Children's Family Contexts in
the United States, 1940-2012.
AB - This article points to a sharp decline in children's sibling numbers (sibsize)
that occurred in the United States since the 1970s and was large enough among
children with lower socioeconomic status (SES) (particularly black children) to
amount to a revolution in their family circumstances. It interprets sibsize
decline as a source of social convergence in children's family contexts that ran
counter to trends toward social divergence caused by the rise of lone parenthood.
The article is based on new estimates of differences in children's sibsize and
lone parenthood by race and maternal education generated from public-use samples
from the Census of Population and Current Population Survey (CPS), focusing
especially on the period 1940-2012. I discuss some methodological and substantive
challenges for existing scholarship arising from the findings and point to
questions for future research.
PMID- 28401502
TI - The effects of age and sex on hand movement structure.
AB - The aim was to investigate the effects of age and sex on hand function and
ascertain age-related changes (magnitude and rate) by assessing a broad range of
functional tasks with the dominant and non-dominant hands. A representative
sample of 635 adults (114 males and 491 females) aged 50 years and over completed
motor performance series of the Vienna Test System Parametric and non-parametric
analysis and simple linear regression was used to examine the relationships.
Significant relationships were observed between task performance and age and sex,
although the contributions of both factors differed by varying degree. Compared
with males, the females performed significantly better than males in the majority
of tests, particularly with the dominant hand, although greater age-related
reductions were observed in performance. Among the skills quantifying hand
function, age accounted for the most variance in hand and finger dexterity.
PMID- 28401503
TI - Shedding light on venoarterial PCO2 gradient.
PMID- 28401504
TI - Metabolism and secretion of yellow pigment under high glucose stress with
Monascus ruber.
AB - The biosynthesis of microbial secondary metabolites is induced by a wide range of
environmental stresses. In this study, submerged fermentation of Monascus yellow
pigments by Monascus ruber CGMCC 10910 under high glucose stress was
investigated. The increase of lipid content was the major contributor to the
increase of dry cell weight (DCW), and the lipid-free DCW was only slightly
changed under high glucose stress, which benefited the accumulation of
intracellular hydrophobic pigments. The fatty acid composition analysis in
Monascus cell membranes showed that high glucose stress significantly increased
the ratio of unsaturated/saturated fatty acid and the index of unsaturated fatty
acid (IUFA) value, which would improve the fluidity and permeability of the cell
membrane. As a consequence, high glucose stress increased extracellular yellow
pigments production by enhancing secretion and trans-membrane conversion of
intracellular pigments to the broth. The total yield of extracellular and
intracellular yellow pigments per unit of lipid-free DCW increased by 94.86 and
26.31% under high glucose stress compared to conventional fermentation,
respectively. A real-time quantitative PCR analysis revealed that the expression
of the pigment biosynthetic gene cluster was up-regulated under high glucose
stress. The gene mppE, which is associated with yellow pigment biosynthesis, was
significantly up-regulated. These results indicated that high glucose stress can
shift the Monascus pigment biosynthesis pathway to accumulate yellow pigments and
lead to a high yield of both extracellular and intracellular yellow pigments.
These findings have potential application in commercial Monascus yellow pigment
production.
PMID- 28401506
TI - The Ethical and Academic Implications of the Jeffrey Beall (www.scholarlyoa.com)
Blog Shutdown.
AB - A very important event took place on January 15, 2017. On that day, the Jeffrey
Beall blog ( www.scholarlyoa.com ) was silently, and suddenly, shut down by Beall
himself. A profoundly divisive and controversial site, the Beall blog represented
an existential threat to those journals and publishers that were listed there. On
the other hand, the Beall blog was a ray of hope to critics of bad publishing
practices that a culture of public shaming was perhaps the only way to rout out
those journals-and their editors-and publishers who did not respect basic
publishing ethical principles and intrinsic academic values. While members of the
former group vilified Beall and his blog, members of the latter camp tried to
elevate it to the level of policy. Split by extreme polar forces, for reasons
still unknown to the public, Beall deliberately shut down his blog, causing some
academic chaos among global scholars, including to the open access movement.
PMID- 28401505
TI - Cardiac Applications of PET-MR.
AB - PURPOSE OF REVIEW: The purpose of this study was to provide an overview of the
clinical applications of PET-MR in the setting of cardiac imaging with emphasis
on specific scenarios where both techniques together provided added information.
RECENT FINDINGS: Synergy of cardiac PET and MR fusion may hold similar promise
eliminating ionizing radiation and improving tissue contrast. Future development
of new hybrid scanners, use of new imaging tracers, and clinical applications are
significant factors which will influence its use. Both positron emission
tomography (PET) and cardiac magnetic resonance imaging (CMR) provide important
anatomic and physiologic information with regard to the heart. Being able to
combine the data from these two examinations in a hybrid technique allows for a
more complete evaluation of cardiac pathology. While hybrid PET-CT has already
established the utility of a combined imaging approach, the use of CMR in lieu of
CT allows for elimination of ionizing radiation and for improved tissue contrast.
PMID- 28401507
TI - Improving Student Engagement in the Study of Professional Ethics: Concepts and an
Example in Cyber Security.
AB - In spite of the acknowledged importance of professional ethics, technical
students often show little enthusiasm for studying the subject. This paper
considers how such engagement might be improved. Four guiding principles for
promoting engagement are identified: (1) aligning teaching content with student
interests; (2) taking a pragmatic rather than a philosophical approach to issue
resolution; (3) addressing the full complexity of real-world case studies; and
(4) covering content in a way that students find entertaining. The use of these
principles is then discussed with respect to the specific experience of
developing and presenting a master's module in Ethical and Legal Issues in Cyber
Security at Queens University Belfast. One significant aspect of the resulting
design is that it encourages students to see ethical issues in systemic terms
rather than from an individual perspective, with issues emerging from a conflict
between different groups with different vested interests. Case studies are used
to examine how personal and business priorities create conflicts that can lead to
negative press, fines and punitive legal action. The module explores the reasons
why organisations may be unaware of the risks associated with their actions and
how an inappropriate response to an ethical issue can significantly aggravate a
situation. The module has been delivered in three successive years since 2014 and
been well received on each occasion. The paper describes the design of the module
and the experience of delivering it, concluding with a discussion of the
effectiveness of the approach.
PMID- 28401508
TI - On Effectiveness and Legitimacy of 'Shaming' as a Strategy for Combatting Climate
Change.
AB - While states have agreed to substantial reduction of emissions in the Paris
Agreement, the success of the Agreement strongly depends on the cooperation of
large Multinational Corporations. Short of legal obligations, we discuss the
effectiveness and moral legitimacy of voluntary approaches based on naming and
shaming. We argue that effectiveness and legitimacy are closely tied together; as
voluntary approaches are the only alternative to legally imposed duties, they are
most morally defensible particularly if they would be the most effective in
reducing the harmful greenhouse gases. Shaming could be made effective if states
could prompt more corporations to accept voluntary cuts with high gains-such as
public acknowledgements-and high losses, such as reporting on noncompliance and
public exposure (naming), along with some kind of condemnation (shaming). An
important challenge of such voluntary approaches is how to ensure compliance with
the agreed upon commitments, while avoiding greenwashing or selective disclosure.
Certain institutional arrangements are inevitable, including an independent
measurement, monitoring and verification mechanism. In this paper, we discuss the
potentials and ethical pitfalls of shaming as a strategy when corporations have a
direct relationship with consumers, but also when they are in a relationship with
governments and other corporations.
PMID- 28401509
TI - From Paper to Practice; Indexing Systems and Ethical Standards.
AB - Currently one of the main goals of editors is to attain a higher visibility for
their journals. On the other hand, authors strive to publish their research in
journals indexed in eminent databases such as Scopus, Thompson Reuters' Web of
Science (ISI), Medline, etc. Therefore, clarifying the standards of indexing is
of great importance. One of the most important issues in publication is the
ethical considerations, which are mainly described by organizations, such as the
International Committee of Medical Journal Editors and the Committee on
Publication Ethics. In this study, we examined the ethical requirements of high
impact databases for indexing journals to investigate whether they mention or
mandate journals to adhere to publication ethics. We found that only Scopus
mandated journals to state clear ethical policies on their website as a criterion
for being indexed while Medline and Directory of Open Access Journals advised
journals to adhere to ethics, not mandated, and Web of Science (ISI) and PubMed
Central made no mention of ethics as a required criterion for indexing. Based on
this short review, there seems to be a gap between the requirements of indexing
systems and international guidelines for publication ethics. Currently, most
indexing systems have only partially recommended journals to consider ethical
issues. In such an atmosphere, we cannot expect journals or as a result, authors
to professionally, completely, and whole heartedly implement ethical guidelines
as a mandatory rule in their journals and research, when the indexing systems
that most editors want to be indexed in and most authors want to be cited in do
not mandate such guidelines.
PMID- 28401510
TI - A Systematic Literature Review of US Engineering Ethics Interventions.
AB - Promoting the ethical formation of engineering students through the cultivation
of their discipline-specific knowledge, sensitivity, imagination, and reasoning
skills has become a goal for many engineering education programs throughout the
United States. However, there is neither a consensus throughout the engineering
education community regarding which strategies are most effective towards which
ends, nor which ends are most important. This study provides an overview of
engineering ethics interventions within the U.S. through the systematic analysis
of articles that featured ethical interventions in engineering, published in
select peer-reviewed journals, and published between 2000 and 2015. As a core
criterion, each journal article reviewed must have provided an overview of the
course as well as how the authors evaluated course-learning goals. In sum, 26
articles were analyzed with a coding scheme that included 56 binary items. The
results indicate that the most common methods for integrating ethics into
engineering involved exposing students to codes/standards, utilizing case
studies, and discussion activities. Nearly half of the articles had students
engage with ethical heuristics or philosophical ethics. Following the
presentation of the results, this study describes in detail four articles to
highlight less common but intriguing pedagogical methods and evaluation
techniques. The findings indicate that there is limited empirical work on ethics
education within engineering across the United States. Furthermore, due to the
large variation in goals, approaches, and evaluation methods described across
interventions, this study does not detail "best" practices for integrating ethics
into engineering. The science and engineering education community should continue
exploring the relative merits of different approaches to ethics education in
engineering.
PMID- 28401512
TI - Erratum to: Increasing Routine Cancer Screening Among Underserved Populations
Through Effective Communication Strategies: Application of a Health Literacy
Framework.
PMID- 28401511
TI - Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 2): Clinical
and Therapeutic Considerations.
AB - Multiple phase III trials over the last few decades have failed to demonstrate a
clear benefit of various pharmacologic interventions in heart failure with a
preserved left ventricular (LV) ejection fraction (HFpEF). Therefore, a better
understanding of its pathophysiology is important. An accompanying review
describes key technical and physiologic aspects regarding the deep phenotyping of
arterial hemodynamics in HFpEF. This review deals with the potential of this
approach to enhance our clinical, translational, and therapeutic approach to
HFpEF. Specifically, the role of arterial hemodynamics is discussed in relation
to (1) the pathophysiology of left ventricular diastolic dysfunction, remodeling,
and fibrosis, (2) impaired oxygen delivery to peripheral skeletal muscle, which
affects peripheral oxygen extraction, (3) the frequent presence of comorbidities,
such as renal failure and dementia in this population, and (4) the potential to
enhance precision medicine approaches. A therapeutic approach to target arterial
hemodynamic abnormalities that are prevalent in this population (particularly,
with inorganic nitrate/nitrite) is also discussed.
PMID- 28401514
TI - A Tribute to the Memory of Susumu Hibino, MD.
PMID- 28401522
TI - Classic Hallucinogens and Mystical Experiences: Phenomenology and Neural
Correlates.
AB - This chapter begins with a brief review of descriptions and definitions of
mystical-type experiences and the historical connection between classic
hallucinogens and mystical experiences. The chapter then explores the empirical
literature on experiences with classic hallucinogens in which claims about
mystical or religious experiences have been made. A psychometrically validated
questionnaire is described for the reliable measurement of mystical-type
experiences occasioned by classic hallucinogens. Controlled laboratory studies
show that under double-blind conditions that provide significant controls for
expectancy bias, psilocybin can occasion complete mystical experiences in the
majority of people studied. These effects are dose-dependent, specific to
psilocybin compared to placebo or a psychoactive control substance, and have
enduring impact on the moods, attitudes, and behaviors of participants as
assessed by self-report of participants and ratings by community observers. Other
studies suggest that enduring personal meaning in healthy volunteers and
therapeutic outcomes in patients, including reduction and cessation of substance
abuse behaviors and reduction of anxiety and depression in patients with a life
threatening cancer diagnosis, are related to the occurrence of mystical
experiences during drug sessions. The final sections of the chapter draw
parallels in human neuroscience research between the neural bases of experiences
with classic hallucinogens and the neural bases of meditative practices for which
claims of mystical-type experience are sometimes made. From these parallels, a
functional neural model of mystical experience is proposed, based on changes in
the default mode network of the brain that have been observed after the
administration of classic hallucinogens and during meditation practices for which
mystical-type claims have been made.
PMID- 28401513
TI - Study of intra-inter species protein-protein interactions for potential drug
targets identification and subsequent drug design for Escherichia coli O104:H4
C277-11.
AB - Protein-protein interaction (PPI) and host-pathogen interactions (HPI) proteomic
analysis has been successfully practiced for potential drug target identification
in pathogenic infections. In this research, we attempted to identify new drug
target based on PPI and HPI computation approaches and subsequently design new
drug against devastating enterohemorrhagic Escherichia coli O104:H4 C277-11
(Broad), which causes life-threatening food borne disease outbreak in Germany and
other countries in Europe in 2011. Our systematic in silico analysis on PPI and
HPI of E. coli O104:H4 was able to identify bacterial D-galactose-binding
periplasmic and UDP-N-acetylglucosamine 1-carboxyvinyltransferase as attractive
candidates for new drug targets. Furthermore, computational three-dimensional
structure modeling and subsequent molecular docking finally proposed [3-(5-Amino
7-Hydroxy-[1,2,3]Triazolo[4,5-D]Pyrimidin-2-Yl)-N-(3,5-Dichlorobenzyl)
Benzamide)] and (6-amino-2-[(1-naphthylmethyl)amino]-3,7-dihydro-8H-imidazo[4,5
g]quinazolin-8-one) as promising candidate drugs for further evaluation and
development for E. coli O104:H4 mediated diseases. Identification of new drug
target would be of great utility for humanity as the demand for designing new
drugs to fight infections is increasing due to the developing resistance and side
effects of current treatments. This research provided the basis for computer
aided drug design which might be useful for new drug target identification and
subsequent drug design for other infectious organisms.
PMID- 28401523
TI - Injection of Pharmaceuticals Designed for Oral Use: Harms Experienced and
Effective Harm Reduction Through Filtration.
AB - Several pharmaceutical products are liable to 'abuse' or use outside their
prescription, which frequently involves their injection. Examples are slow
release forms of morphine and oxycodone, and sublingual buprenorphine. During
injection preparation, the drug is extracted into water, after crushing and
heating the tablet if considered necessary. Since these products are designed for
oral administration, they can contain excipients (ingredients other than the
drug) which are poorly soluble, resulting in suspension of particles in the
injection solution. Injected particles are able to produce medical complications
such as the blockage of small blood vessels leading to ischaemia (inadequate
blood flow) and tissue damage. Filtration can be used to remove particles from
the suspension; including bacteria if the porosity is small enough (0.2 MUm).
However, filters are liable to blockage when overloaded, especially if the pore
size is small. This problem can be minimised by using a larger pore size (e.g. 5
10 MUm), but the resulting filtrate will contain many residual small particles.
The use of two filters, coarse and fine, either sequentially or in a double
membrane device, enables removal of the majority of particles as well as
bacteria, although not quite meeting pharmaceutical standards for safe injection.
Although not yet evaluated by a clinical trial, this highly effective filtration
process would be expected to greatly reduce the risk of vascular and related
complications, as well as non-viral infections. Careful technique ensures that
drug is not lost by filtration, a priority for most drug consumers. Practical
issues that affect acceptability of filtration by injecting drug users, including
ease of use and cost, will need to be considered. However, given the laboratory
evidence demonstrating the effectiveness of filters it is time to consider these
tools as essential for safe injection as sterile needles/syringes for the world's
approximately 16 million people who inject drugs.
PMID- 28401524
TI - Chemistry and Structure-Activity Relationships of Psychedelics.
AB - This chapter will summarize structure-activity relationships (SAR) that are known
for the classic serotonergic hallucinogens (aka psychedelics), focusing on the
three chemical types: tryptamines, ergolines, and phenethylamines. In the brain,
the serotonin 5-HT2A receptor plays a key role in regulation of cortical function
and cognition, and also appears to be the principal target for
hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively
studied of the 14 known types of serotonin receptors. Important structural
features will be identified for activity and, where possible, those that the
psychedelics have in common will be discussed. Because activation of the 5-HT2A
receptor is the principal mechanism of action for psychedelics, compounds with 5
HT2A agonist activity generally are quickly discarded by the pharmaceutical
industry. Thus, most of the research on psychedelics can be related to activation
of 5-HT2A receptors. Therefore, much of the discussion will include not only
clinical or anecdotal studies, but also will consider data from animal models as
well as a certain amount of molecular pharmacology where it is known.
PMID- 28401525
TI - New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.
AB - New World indigenous peoples are noted for their sophisticated use of psychedelic
plants in shamanic and ethnomedical practices. The use of psychedelic plant
preparations among New World tribes is far more prevalent than in the Old World.
Yet, although these preparations are botanically diverse, almost all are
chemically similar in that their active principles are tryptamine derivatives,
either DMT or related constituents. Part 1 of this paper provides an
ethnopharmacological overview of the major tryptamine-containing New World
hallucinogens. Part 2 focuses on ayahuasca and its effects on the human brain.
Using complementary neurophysiological and neuroimaging techniques, we have
identified brain areas involved in the cognitive effects induced by this complex
botanical preparation. Initial SPECT data showed that ayahuasca modulated
activity in higher order association areas of the brain. Increased blood
perfusion was observed mainly in anterior brain regions encompassing the
frontomedial and anterior cingulate cortices of the frontal lobes, and in the
medial regions of the temporal lobes. On the other hand, applying spectral
analysis and source location techniques to cortical electrical signals, we found
changes in neuronal activity that predominated in more posterior sensory
selective areas of the brain. Now, using functional connectivity analysis of
brain oscillations we have been able to reconcile these seemingly contradictory
findings. By measuring transfer entropy, a metric based on information theory, we
have shown that ayahuasca temporarily modifies the ordinary flow of information
within the brain. We propose a model in which ayahuasca reduces top-down
constraints and facilitates bottom-up information transfer. By simultaneously
enhancing endogenous cortical excitability and reducing higher-order cognitive
control, ayahuasca temporarily disrupts neural hierarchies allowing inner
exploration and a new outlook on reality.
PMID- 28401526
TI - The fight between a dwarf and a stork (Mosaic I century BC).
PMID- 28401527
TI - Fluid intelligence, traits of personality and personality disorders in a cohort
of adult KS patients with the classic 47, XXY karyotype.
AB - PURPOSE: Klinefelter's syndrome (KS) is associated with specific neurobehavioral
features and personality traits. The aim of our study was to investigate fluid
intelligence, personality traits and personality disorders (PD) and possible
correlations with testosterone in a cohort of adult KS patients. METHODS: We
analyzed 58 adult KS patients with the classic 47, XXY karyotype. The Structured
Clinical Interview for axis II disorders was used to assess DSM IV personality
disorders. Personality traits were assessed using MMPI-2. Fluid intelligence was
tested by using Raven's Standard Progressive Matrices (SPM) Test. Testosterone
blood concentration was measured by CMIA. RESULTS: PD prevalence was 31%. Four
altered MMPI scales (Social Responsibility, Dominance, Ego Strength and
Repression) were found in more than 40% of patients. Overcontrolled hostility and
MacAndrew Alcoholism Scale-Revised scales were altered in the PD- group only. Biz
Odd Thinking and Post-Traumatic Stress Disorder scale were associated with the
presence of personality disorder. The raw SPM score was 44 +/- 10.8 without any
significant correlation with testosterone. No significant difference in mean age,
SPM raw score and MMPI score was observed between eugonadal, hypogonadal and
treated patients. CONCLUSIONS: Most KS patients had average fluid intelligence.
PD prevalence was higher than in the general population. Testosterone was not
correlated with fluid intelligence, personality traits or PD, but a reduction in
marital distress was observed in treated patients. This could suggest that
testosterone therapy can improve physical symptoms and this effect could also
improve relationship abilities and wellness awareness.
PMID- 28401529
TI - Influence of exercise intervention on gestational diabetes mellitus: a systematic
review and meta-analysis.
AB - AIMS: Exercise intervention might be a promising approach to prevent gestational
diabetes mellitus. However, the results remained controversial. We conducted a
systematic review and meta-analysis to explore the effect of exercise
intervention on gestational diabetes mellitus. METHODS: PubMed, EMbase, Web of
science, EBSCO, and Cochrane library databases were systematically searched.
Randomized controlled trials (RCTs) assessing the effect of exercise intervention
on gestational diabetes mellitus were included. Two investigators independently
searched articles, extracted data, and assessed the quality of included studies.
The primary outcome was the incidence of gestational diabetes mellitus, preterm
birth, and gestational age at birth. Meta-analysis was performed using random
effect model. RESULTS: Five RCTs involving 1872 patients were included in the
meta-analysis. Overall, compared with control intervention, exercise intervention
was found to significantly reduce the risk of gestational diabetes mellitus (std.
mean difference 0.62; 95% CI 0.43-0.89; P = 0.01), but demonstrated no influence
on preterm birth (OR 0.93; 95% CI 0.44-1.99; P = 0.86), gestational age at birth
(std. mean difference -0.03; 95% CI -0.12 to 0.07; P = 0.60), glucose 2-h post
OGTT (std. mean difference -1.02; 95% CI -2.75 to 0.71; P = 0.25), birth weight
(std. mean difference -0.10; 95% CI -0.25 to 0.04; P = 0.16), Apgar score less
than 7 (OR 0.78; 95% CI 0.21-2.91; P = 0.71), and preeclampsia (OR 1.05; 95% CI
0.53-2.07; P = 0.88). CONCLUSIONS: Compared to control intervention, exercise
intervention was found to significantly reduce the incidence of gestational
diabetes mellitus, but had no significant influence on preterm birth, gestational
age at birth, glucose 2-h post-OGTT, birth weight, Apgar score less than 7, and
preeclampsia.
PMID- 28401528
TI - Association between low C-peptide and fragility fractures in postmenopausal women
without diabetes.
AB - PURPOSE: C-peptide has been shown to exert several, previously unknown,
biological effects. A recent cross-sectional study demonstrated an association
between low C-peptide serum levels and low lumbar bone density of postmenopausal
women not affected by diabetes. To date, very little research attention has been
directed toward the association between C-peptide and osteoporotic fractures. To
contribute toward filling this gap, we investigated the association between C
peptide and fractures in postmenopausal women. METHODS: A cohort of 133 non
diabetic postmenopausal women with and without a history of fractures was
evaluated in this cross-sectional investigation. Standardized interviews were
performed to gather information on the patients' fracture history. All of the
participants underwent a bone mineral density assessment by DXA, radiographs, and
a serum C-peptide measurement. RESULTS: Thirty-four women presented fractures.
Bivariate analysis revealed an inverse correlation between C-peptide and
fractures (r = -0.27, p = 0.002). A significant difference in mean C-peptide
levels was also found between women with vs. without fractures (p = 0.01,
adjusted for age, BMI and glucose). Logistic regression analysis showed that C
peptide levels, femoral and vertebral BMD were all negatively associated with
fracture status (B = -1.097, ES = 0.401, p = 0.006, 95% CI 0.15-0.73; B = -15.6,
SE = 4.17, p < 0.001, CI 0.001-0.002; B = -24.8, SE = 5.23, p < 0.001, CI 0001
0.002; respectively). CONCLUSIONS: This study confirms an inverse association
between serum C-peptide levels and a history of fractures in postmenopausal women
without diabetes. These results suggest that C-peptidemay exert an effect on bone
mineral density. However, further large-scale studies are needed to corroborate
this finding and investigate the potential underlying mechanisms involved.
PMID- 28401530
TI - A plug-and-play pathway refactoring workflow for natural product research in
Escherichia coli and Saccharomyces cerevisiae.
AB - Pathway refactoring serves as an invaluable synthetic biology tool for natural
product discovery, characterization, and engineering. However, the complicated
and laborious molecular biology techniques largely hinder its application in
natural product research, especially in a high-throughput manner. Here we report
a plug-and-play pathway refactoring workflow for high-throughput, flexible
pathway construction, and expression in both Escherichia coli and Saccharomyces
cerevisiae. Biosynthetic genes were firstly cloned into pre-assembled helper
plasmids with promoters and terminators, resulting in a series of expression
cassettes. These expression cassettes were further assembled using Golden Gate
reaction to generate fully refactored pathways. The inclusion of spacer plasmids
in this system would not only increase the flexibility for refactoring pathways
with different number of genes, but also facilitate gene deletion and
replacement. As proof of concept, a total of 96 pathways for combinatorial
carotenoid biosynthesis were built successfully. This workflow should be
generally applicable to different classes of natural products produced by various
organisms. Biotechnol. Bioeng. 2017;114: 1847-1854. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28401531
TI - Exercise during pregnancy and risk of gestational hypertensive disorders: a
systematic review and meta-analysis.
AB - INTRODUCTION: Gestational hypertensive disorders, including gestational
hypertension and preeclampsia, are one of the leading causes of maternal
morbidity and mortality. The aim of our study was to evaluate the effect of
exercise during pregnancy on the risk of gestational hypertensive disorders.
MATERIAL AND METHODS: Electronic databases were searched from their inception to
February 2017. Selection criteria included only randomized controlled trials of
uncomplicated pregnant women assigned before 23 weeks to an aerobic exercise
regimen or not. The summary measures were reported as relative risk with 95%
confidence intervals. The primary outcome was the incidence of gestational
hypertensive disorders, defined as either gestational hypertension or
preeclampsia. RESULTS: Seventeen trials, including 5075 pregnant women, were
analyzed. Of them, seven contributed data to quantitative meta-analysis for the
primary outcome. Women who were randomized in early pregnancy to aerobic exercise
for about 30-60 min two to seven times per week had a significant lower incidence
of gestational hypertensive disorders (5.9% vs. 8.5%; relative risk 0.70, 95%
confidence interval 0.53-0.83; seven studies, 2517 participants), specifically a
lower incidence of gestational hypertension (2.5% vs. 4.6%; relative risk 0.54,
95% confidence interval 0.40-0.74; 16 studies, 4641 participants) compared with
controls. The incidence of preeclampsia (2.3% vs. 2.8%; relative risk 0.79, 95%
confidence interval 0.45-1.38; six studies, 2230 participants) was similar in
both groups. The incidence of cesarean delivery was decreased by 16% in the
exercise group. CONCLUSIONS: Aerobic exercise for about 30-60 min two to seven
times per week during pregnancy, as compared with being more sedentary, is
associated with a significantly reduced risk of gestational hypertensive
disorders overall, gestational hypertension, and cesarean delivery.
PMID- 28401532
TI - Gram-positive pneumonia augments non-small cell lung cancer metastasis via host
toll-like receptor 2 activation.
AB - Surgical resection of early stage nonsmall cell lung cancer (NSCLC) is necessary
for cure. However, rates of postoperative bacterial pneumonias remain high and
may confer an increased risk for metastasis. Toll-like receptors (TLRs) mediate
the inflammatory cascade by recognizing microbial products at the surface of
numerous cell types in the lung; however, little is known about how host TLRs
influence NSCLC metastasis. TLR2 recognizes gram-positive bacterial cell wall
components activating innate immunity. We demonstrate that lower respiratory
tract infection with Streptococcus pneumonia augments the formation of murine H59
NSCLC liver metastases in C57BL/6 mice through host TLR2 activation. Infected
mice demonstrate increased H59 and human A549 NSCLC adhesion to hepatic sinusoids
in vivo compared with noninfected controls, a response that is significantly
diminished in TLR2 knock-out mice. Intra-tracheal injection of purified TLR2
ligand lipoteichoic acid into mice similarly augments in vivo adhesion of H59
cells to hepatic sinusoids. Additionally, H59 and A549 NSCLC cells incubated with
bronchoepithelial conditioned media show increased cell adhesion to extracellular
matrix components in vitro and hepatic sinusoids in vivo in a manner that is
dependent on bronchoepithelial TLR2 activation and interleukin-6 secretion. TLR2
is therefore a potential therapeutic target for gram-positive pneumonia-driven
NSCLC metastasis.
PMID- 28401533
TI - Long-term follow-up of fenestrated endovascular repair for juxtarenal aortic
aneurysm.
AB - BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly
being used for juxtarenal aortic aneurysms. The aim of this study was to review
long-term results and assess the importance of changing stent-graft design on
outcomes. METHODS: This was a retrospective review of all patients who underwent
FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan
Meier analysis of survival, and freedom from target vessel loss, aneurysm
expansion, graft-related endoleak and secondary intervention was performed.
Comparison between outcomes of less complex grafts (fewer than 3 fenestrations)
and more complex grafts (3 or 4 fenestrations) was undertaken. RESULTS: Some 173
patients underwent FEVAR; median age was 76 (i.q.r. 70-79) years and 90.2 per
cent were men. Median aneurysm diameter was 63 (59-71) mm and median follow-up
was 34 (16-50) months. The adjusted primary technical operative success rate was
95.4 per cent. The in-hospital mortality rate was 5.2 per cent; there was no
known aneurysm-related death during follow-up. Median survival was 7.1 (95 per
cent c.i. 5.2 to 8.1) years and overall survival was 60.1 per cent (104 of 173).
There was a trend towards an increasing number of fenestrations in the graft
design over time. In-hospital mortality appeared higher when more complex stent
grafts were used (8 versus 2 per cent for stent-grafts with 3-4 versus fewer than
3 fenestrations; P = 0.059). Graft-related endoleaks were more common following
deployment of stent-grafts with three or four fenestrations (12 of 90 versus 6 of
83; P < 0.001). CONCLUSION: Fenestrated endovascular aneurysm repair for
juxtarenal aneurysm is associated with few aneurysm-related deaths in the long
term. Significant numbers of secondary interventions are required, but the
majority of these can be performed using an endovascular approach.
PMID- 28401534
TI - Competing risks analysis of microsatellite instability as a prognostic factor in
colorectal cancer.
AB - BACKGROUND: Despite an extensive literature suggesting that high microsatellite
instability (MSI-H) enhances survival and protects against recurrence after
colorectal cancer resection, such effects remain controversial as many studies
show only a weak bivariate association or no multivariable association with
outcome. This study examined the relationship between MSI status and colorectal
cancer outcomes with adjustment for death from other causes as a competing risk.
METHODS: A hospital database of patients following colorectal cancer resection
was interrogated for clinical, operative, pathology, adjuvant therapy and follow
up information. MSI-H status was determined by immunohistochemistry for mismatch
repair protein deficiency. The cumulative incidence of recurrence and colorectal
cancer-specific death was evaluated by competing risks methods. RESULTS: Among
1009 patients who had a resection between August 2002 and December 2008, and were
followed to at least December 2013, there were 114 (11.3 per cent) with MSI-H
(72.8 per cent aged at least 70 years; 63.2 per cent women). After potentially
curative resection, with adjustment for non-colorectal cancer death as a
competing risk and adjustment for 22 clinical, operative and pathological
variables, there was no association between MSI-H and recurrence (hazard ratio
(HR) 0.81, 95 per cent c.i. 0.42 to 1.57) or colorectal cancer-specific death (HR
0.73, 0.39 to 1.35) in this patient population. For palliative resections, there
was no association between MSI-H and colorectal cancer-specific death (HR 0.65,
0.21 to 2.04). MSI-H was associated with non-colorectal cancer death after both
curative (HR 1.55, 1.04 to 2.30) and palliative (HR 3.80, 1.32 to 11.00)
resections. CONCLUSION: Microsatellite instability status was not an independent
prognostic variable in these patients.
PMID- 28401535
TI - Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by
modulating critical intracellular pathways.
AB - Although, intracellular signaling pathways are proposed to predict the quality of
cell-surface relationship, this study addressed pre-osteoblast behavior in
response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring
critical intracellular pathways and pre-osteoblast morphological change.
Physicochemical properties were evaluated by atomic force microscopy (AFM) and
wettability considering water contact angle of three differently texturized Ti
surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite
blasted (nHA). The results revealed critical differences in surface topography,
impacting the water contact angle and later the osteoblast performance. In order
to evaluate the effect of those topographical characteristics on biological
responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and
subjected the cultures to biological analysis. First, we have observed pre
osteoblasts morphological changes resulting from the interaction with the Ti
texturized surfaces whereas the cells cultured on nHA presented a more advanced
spreading process when compared with the cells cultured on the other surfaces.
These results argued us for analyzing the molecular machinery and thus, we have
shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti
apoptotic effect, maybe explained by the fact that HA is a natural element
present in bone composition. Thereafter, we investigated the potential effect of
those surfaces on promoting pre-osteoblast adhesion and survival signaling by
performing crystal violet and immunoblotting approaches, respectively. Our
results showed that nHA promoted a higher pre-osteoblast adhesion supported by up
modulating FAK and Src activations, both signaling transducers involved during
eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all
evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able
to promote osteoblast differentiation up to 10 days, when alkaline phosphatase
(ALP) activity and osteogenic transcription factors were up-modulated.
Altogether, our results showed for the first time that nano hydroxyapatite
blasted titanium surface promotes crucial intracellular signaling network
responsible for cell adapting on the Ti-surface.Biotechnol. Bioeng. 2017;114:
1888-1898. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401536
TI - Autodisplay of glucose-6-phosphate dehydrogenase for redox cofactor regeneration
at the cell surface.
AB - Inherent cofactor regeneration is a pivotal feature of whole cell biocatalysis.
For specific biotechnological applications, surface display of enzymes is
emerging as a tool to circumvent mass transfer limitations or enzyme stability
problems. Even complex reactions can be accomplished applying displayed enzymes.
Yet, industrial utilization of the technique is still impeded by lacking cofactor
regeneration at the cell surface. Here, we report on the surface display of a
glucose-6-phoshate dehydrogenase (G6PDH) via Autodisplay to address this
limitation and regenerate NADPH directly at the cell surface. The obtained whole
cell biocatalyst demonstrated similar kinetic parameters compared to the purified
enzyme, more precisely KM values of 0.2 mM for NADP+ and calculated total
turnover numbers of 107 . However, the KM for the substrate G6P increased by a
factor of 7 to yield 1.5 mM. The whole cell biocatalyst was cheaper to produce,
easy to separate from the reaction mixture and reusable in consecutive reaction
cycles. Furthermore, lyophilization allowed storage at room temperature. The
whole cell biocatalyst displaying G6PDH was applicable for NADPH regeneration in
combination with soluble as well as surface displayed enzymes and model reactions
in combination with bacterial CYP102A1 and human CYP1A2 were realized.
Biotechnol. Bioeng. 2017;114: 1658-1669. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401537
TI - Effect of prophylactic placement of internal iliac artery balloon catheters on
outcomes of women with placenta accreta: an impact study.
AB - We performed an impact study on the introduction of routine placement of internal
iliac artery balloon catheters for the management of haemorrhage during caesarean
section in women with placenta accreta. We identified 11 women, with prenatally
diagnosed placenta accreta/increta/percreta before this change in practice, who
acted as controls, and 30 women who had iliac artery balloons placed. The
balloons were inflated in 27 cases. The median (IQR [range]) intra-operative
blood loss was 1100 (800-2600 [500-6000]) ml in controls, compared with 1000 (600
2513 [400-15000]) ml in women with iliac artery balloons (p = 0.64). Six (54%)
controls received intra-operative blood transfusion compared with 14 (47%) women
with iliac artery balloons (p = 0.66). Caesarean hysterectomy was performed in 3
(27.3%) controls and 13 (43.3%) women with iliac artery balloons (p = 0.48).
Balloon catheter insertion was associated with a shortened postoperative hospital
stay, 6 (5-7 [4-12] days in controls vs. 5 (4-6 [3-10]) in the iliac artery
balloon group (p = 0.033). General anaesthesia was used in six (54%) controls,
but all women with iliac artery balloons. This study demonstrates that
prophylactic balloon occlusion of the internal iliac arteries did not reduce
intra-operative haemorrhage or caesarean hysterectomy in women with placenta
accreta undergoing caesarean section. In addition, it has a significant impact on
the choice of anaesthetic technique.
PMID- 28401539
TI - Leprosy clinically masquerading as necrobiotic xanthogranuloma: a
histopathological surprise!
PMID- 28401538
TI - Women's attitude towards routine human platelet antigen-screening in pregnancy.
AB - INTRODUCTION: Fetal and neonatal alloimmune thrombocytopenia is a potentially
life-threatening disease with excellent preventative treatment available for
subsequent pregnancies. To prevent index cases, the effectiveness of a population
based screening program has been suggested repeatedly. Therefore, we aimed to
evaluate women's attitude towards possible future human platelet antigen
screening in pregnancy. MATERIAL AND METHODS: We performed a cross-sectional
questionnaire study among healthy pregnant women receiving prenatal care in one
of seven participating midwifery practices. Attitude was assessed using a
questionnaire based on the validated Multidimensional Measurement of Informed
Choice model, containing questions assessing knowledge, attitude and intention to
participate. RESULTS: A total of 143 of the 220 women (65%) completed and
returned the questionnaire. A positive attitude towards human platelet antigen
screening was expressed by 91% of participants, of which 94% was based on
sufficient knowledge. Attitude was more likely to be negatively influenced by the
opinion that screening can be frightening. Informed choices were made in 87% and
occurred significantly less in women from non-European origin, 89% in European
women vs. 60% in non-European women (p = 0.03). CONCLUSIONS: Pregnant women in
the Netherlands expressed a positive attitude towards human platelet antigen
screening in pregnancy. We therefore expect a high rate of informed uptake when
human platelet antigen-screening is implemented. In future counseling on human
platelet antigen-screening, ethnicity and possible anxiety associated with a
screening test need to be specifically addressed.
PMID- 28401540
TI - Two novel MYLK nonsense mutations causing thoracic aortic aneurysms/dissections
in patients without apparent family history.
PMID- 28401541
TI - Prevalence of urinary incontinence among women and analysis of potential risk
factors in Germany and Denmark.
AB - INTRODUCTION: Urinary incontinence (UI) is a prevalent condition that interferes
with women's health-related quality of life. Prevalence rates from earlier
studies are wide-ranging, due to heterogeneity in methodology, definition of UI
and the populations included. We aimed to determine the prevalence of UI and
associated risk factors in Germany and Denmark using the same methodology,
definition and population. MATERIAL AND METHODS: A postal survey was conducted in
two regions in Germany and Denmark, including 8000 women aged 18+ years. UI was
defined as any complaint of involuntary loss of urine. The questionnaire
contained socio-demographic questions and the International Consultation on
Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF).
RESULTS: The response rate in Germany and Denmark was 46.2 and 66.6% (p < 0.001)
and the prevalence rate of UI was 48.3 and 46.4% (p = 0.188), respectively.
Stress urinary incontinence dominated among younger women, and urgency urinary
incontinence and mixed urinary incontinence among women 80+ years in Germany and
Denmark, respectively. The subgroup of women with body mass index (BMI) >=35 had
the highest prevalence of UI (67.3%). The subgroup of women with BMI <35 were
more likely to have stress urinary incontinence, and the subgroup of women with
BMI >=35 were more likely to have mixed urinary incontinence. UI was
significantly associated with age as with BMI, vaginal delivery, chronic
obstructive pulmonary disease, and having at least one co-morbidity. CONCLUSIONS:
Prevalence rates in the two regions in Germany and Denmark were similar, despite
significantly different response rates. This difference may reflect various
attitudes towards answering a questionnaire, but the response rate on questions
concerning UI seemed consistent.
PMID- 28401543
TI - Fascia iliaca block for hip replacement - adjuvants and ethics. A reply.
PMID- 28401544
TI - Fascia iliaca block for hip replacement - adjuvants and ethics.
PMID- 28401542
TI - Quality of life after mastectomy with or without immediate breast reconstruction.
AB - BACKGROUND: Mastectomy with immediate breast reconstruction (IBR) is a surgical
strategy in breast cancer when breast-conserving surgery is not an option. There
is a lack of evidence showing an advantage of mastectomy plus IBR over mastectomy
alone on health-related quality of life (QoL). METHODS: A large prospective
multicentre survey, STIC-RMI (support of innovative and expensive techniques -
immediate breast reconstruction), was undertaken to study the changes in QoL in
patients treated by mastectomy with or without IBR. Patients were recruited
between 2007 and 2009. European Organisation for Research and Treatment of Cancer
QLQ-C30 and QLQ-BR23 instruments were used to assess QoL before operation, and at
6 and 12 months after surgery. A propensity score was used to compare QoL between
mastectomy alone and mastectomy plus IBR, with limited bias. RESULTS: A total of
595 patients were included from 22 French academic hospitals, of whom 407 (68.4
per cent) underwent IBR. One-year data were available for 71.1 per cent of
patients. Factors associated with IBR were age, histological tumour type,
palpable nodes and an attempt at breast-conserving surgery. At inclusion, QoL was
significantly better in the IBR group (P < 0.001) and there was no significant
change in either group during 1 year compared with baseline. Results for the QLQ
BR23 functional dimension varied according to propensity score quartiles; IBR had
no influence in the lowest quartile. In the upper quartiles, QoL increased
slightly over the year among patients who had IBR, whereas it decreased among
those who had mastectomy alone (P = 0.037). Satisfaction with the cosmetic
outcome strongly influenced QoL, especially in upper quartiles (P < 0.001).
However, an unsatisfactory outcome after IBR was still considered a better
condition than simple mastectomy. CONCLUSION: The QoL benefit provided by IBR
depends on patients' life status at inclusion; young active women with an in situ
tumour are more likely to preserve their QoL after IBR.
PMID- 28401545
TI - Non-sticky sticky syringe labels.
PMID- 28401546
TI - Cerebral oxygenation and vascular resistance changes during cardiopulmonary
bypass - where is the proof?
PMID- 28401547
TI - Should blood glucose measurement be a standard of monitoring? A reply.
PMID- 28401548
TI - Cerebral oxygenation and vascular resistance changes during cardiopulmonary
bypass - where is the proof? A reply.
PMID- 28401549
TI - Mock before you block.
PMID- 28401550
TI - AAGBI Consent for Anaesthesia 2017 guidelines - a reply.
PMID- 28401551
TI - Should blood glucose measurement be a standard of monitoring?
PMID- 28401552
TI - AAGBI Consent guidelines 2017 - should the advice about 16 and 17-year-olds be
amended?
PMID- 28401553
TI - An alternative to the best interests standard for consent in paediatrics.
PMID- 28401554
TI - Self-harm and poisoning data in rural Ugandan hospitals - a reply.
PMID- 28401556
TI - Is the anaesthetic consent process now too onerous?
PMID- 28401555
TI - Self-harm and poisoning data in rural Ugandan hospitals.
PMID- 28401557
TI - Mock before you block - a reply.
PMID- 28401558
TI - 2016 RANZCOG Ian McDonald Memorial Oration: 'The whole nine months lasts a
lifetime': Delivered at RANZCOG Annual Scientific Meeting, Perth, 17th October
2016.
PMID- 28401559
TI - Response to Transvaginal mesh - let's not repeat the mistakes of the past.
PMID- 28401560
TI - Down syndrome screening in the 21st century - More inequitable than ever.
PMID- 28401561
TI - Pregnant women's attitudes toward antenatal pertussis vaccination.
PMID- 28401562
TI - Response to The mesh debate: Transvaginal anterior anchored mesh should not be
abandoned.
PMID- 28401563
TI - Twelve month follow-up of a contraceptive implant outreach service in rural Papua
New Guinea.
AB - BACKGROUND: Poor access to contraception contributes to persistently high
maternal mortality rates in Papua New Guinea (PNG). Since 2012 contraceptive
implants have been provided to women in rural areas of PNG through outreach
services but follow-up data in these communities on continuation and
acceptability is lacking. OBJECTIVE: To gain insight into women's experience with
contraceptive implants by assessing the acceptability, satisfaction, 12 month
continuation rates and efficacy of contraceptive implants among women in rural
PNG. MATERIAL AND METHODS: We undertook a cross-sectional survey of women in two
rural provinces who had received a contraceptive implant at least 12 months prior
using a structured questionnaire. We sought information on device continuation
rates, satisfaction scores, side effects and failure rates. RESULTS: Of the 860
women surveyed, 97% (n = 836) still had the device in situ after 12 months and
92% (n = 793) were very happy with it. Seventy-six percent of women (n = 654)
reported no side effects. Irregular bleeding was the most commonly reported side
effect (n = 178, 20.6%) but only 7% (n = 13) said the bleeding was bothersome.
Documented failure rates were 0.8% although pregnancy at the time of insertion
could not be excluded in any of these cases. CONCLUSION: Twelve month implant
follow-up data in this study showed high continuation rates and high levels of
satisfaction among a rural population in PNG. Implants have the potential to
lower maternal morbidity and mortality and simultaneously address the unmet need
for contraception in these communities.
PMID- 28401565
TI - Serum and exosomal miR-122 and miR-199a as a biomarker to predict therapeutic
efficacy of hepatitis C patients.
AB - MicroRNA (miRNA), which has been shown to correlate with liver functions, has
been proposed as a new biomarker reflecting liver injury. The aim of the study
was to investigate miRNA-122 (miR-122) and mir-RNA-199a (miR-199a) as a biomarker
for predicting therapeutic efficacy in hepatitis C (HepC) patients. A total of 47
HepC 1b patients and 16 healthy subjects were enrolled in the study. Serum and
exosomal mir-RNAs and other conventional biomarkers reflecting liver function
were evaluated. The miR-122 levels in serum (miR-122ser ) and exosomes (miR
122exo ) were significantly lower in the Hepatitis C virus (HCV) genotype 1b
patients than in the normal controls, but these levels were higher compared to
the non-genotype 1b group. The mean miR-122ser level in the sustained virological
response (SVR) group was significantly higher than that in the non-response (NR)
group (P < 0.01), and the miR-122exo level in the SVR group was also higher than
that in the NR group (P > 0.05), although this difference was not significant.
miR-199a levels showed similar trends with the miR-122 levels in serum and
exosomes. HCV RNAser was negatively correlated with the miR-122ser (r = -0.473, P
= 0.004) and miR-122exo (r = -0.424, P = 0.009) levels. miR-122ser levels were
positively associated with miR-199aser levels (r = 0.453, P = 0.002). Univariate
and multivariate regression analyses reveal that the miR-122ser levels and
ALT/AST ratio demonstrated a predictive value in evaluating patient outcomes.
Serum miR-122 and miR-199a are potential biomarkers that reflect therapeutic
efficacy.
PMID- 28401564
TI - A Double-Blind Randomized Placebo-Controlled Trial of Oral Naltrexone for Heavy
Drinking Smokers Seeking Smoking Cessation Treatment.
AB - BACKGROUND: Post hoc analyses of 2 randomized controlled trials suggest
naltrexone may reduce alcohol use and improve smoking cessation outcomes among
heavy drinkers receiving smoking cessation treatment. However, no studies have
been conducted specifically to examine naltrexone for this purpose or to test
whether naltrexone has benefit when added to smoking cessation counseling that
explicitly addresses heavy drinking. METHODS: We recruited heavy-drinking smokers
from the community and randomized them to receive 10 weeks of either (i) 50 mg
naltrexone (n = 75) or (ii) placebo (n = 75) daily. Participants received 6 weeks
of transdermal nicotine patch and 6 sessions of counseling that addressed both
heavy drinking and smoking. Participants were followed for 26 weeks after their
target quit smoking date. RESULTS: Across medication conditions, there were
substantial reductions at follow-up in percent heavy drinking days (primary
outcome) and average drinks per week (secondary outcome). However, participants
receiving naltrexone did not differ significantly from those receiving placebo on
percent heavy drinking days (effect size d = -0.04, 95% CI [-0.30, 0.22], p =
0.76) or average drinks per week (d = -0.09, 95% CI [-0.35, 0.18], p = 0.54)
during follow-up. Naltrexone compared to placebo was not associated with a
significant increase in smoking abstinence rates during follow-up, odds ratio =
0.93, 95% CI [0.46, 1.86], p = 0.83. The effect of naltrexone on these outcomes
was not significantly moderated by current alcohol dependence or gender.
CONCLUSIONS: Results indicate that heavy-drinking smokers, including those with
current alcohol dependence, can make substantial reductions in drinking in the
context of smoking cessation treatment. However, this study provided no evidence
that naltrexone is efficacious for enhancing reductions in drinking or improving
smoking cessation in this population. Limitations of this study included lower
than-desired sample size and modest adherence to study medication.
PMID- 28401566
TI - Plasma pharmacokinetics and muscle residue dynamics of mebendazole in Carassius
auratus.
AB - Mebendazole is approved for use in aquatic animals and is widely used in Chinese
aquaculture. We developed a pharmacokinetic and residue analysis for mebendazole
levels in the goldfish (Carassius auratus). Plasma and muscle samples of C.
auratus were taken after oral administration of 10 mg/kg mebendazole. The maximal
drug plasma concentration of 0.55 mg/L was achieved at 48 hr and then declined
with the elimination half-life (T1/2beta ) of 7.99 hr. Administration of 10 mg/kg
by oral gavage for 5 successive days resulted in a peak mebendazole concentration
of 0.70 mg/kg in muscle at 96 hr after the last dose. The drug was then
eliminated at a relatively slow rate from muscle with T1/2beta of 68.41 hr. There
was no detectable mebendazole in any muscle samples at 24 days
postadministration. The AUClast in plasma and muscle was 19.42 and 105.33 mg
hr/L, respectively. These data provide information for dosage recommendations and
withdrawal time determinations for mebendazole use in aquariums.
PMID- 28401567
TI - Arnica montana L. - a plant of healing: review.
AB - OBJECTIVES: Arnica montana is a widely used therapeutic plant used traditionally
to treat various ailments. The objective of this study was to evaluate the
botany, phytochemistry and ethnopharmacology along with special emphasis given on
pharmacological activity of plant A. montana. KEY FINDINGS: The plant extracts
have been reported to possess antibacterial, antitumor, antioxidant, anti
inflammatory, antifungal and immunomodulatory activity. A wide range of chemical
compounds including sesquiterpene lactones and their short-chain carbonic acid
esters, flavonoids, carotenoids, essential oils, diterpenes, arnidiol,
pyrrolizidine alkaloids, coumarins, phenolic acids, lignans and oligosaccharides,
etc., are found in different parts of the plant. SUMMARY: It has been scrutinized
that extensive research has been carried out to explore the therapeutic potential
of flowers of the plant. Therefore, investigations should be carried out to
explore the therapeutic potential of other parts of the plant for better
therapeutic utilization.
PMID- 28401568
TI - A secreted chitinase-like protein (OsCLP) supports root growth through calcium
signaling in Oryza sativa.
AB - Chitinases belong to a conserved protein family and play multiple roles in
defense, development and growth regulation in plants. Here, we identified a
secreted chitinase-like protein, OsCLP, which functions in rice growth. A T-DNA
insertion mutant of OsCLP (osclp) showed significant retardation of root and
shoot growth. A comparative proteomic analysis was carried out using root tissue
of wild-type and the osclp mutant to understand the OsCLP-mediated rice growth
retardation. Results obtained revealed that proteins related to glycolysis
(phosphoglycerate kinase), stress adaption (chaperonin) and calcium signaling
(calreticulin and CDPK1) were differentially regulated in osclp roots. Fura-2
molecular probe staining, which is an intracellular calcium indicator, and
inductively coupled plasma-mass spectrometry (ICP-MS) analysis suggested that the
intracellular calcium content was significantly lower in roots of osclp as
compared with the wild-type. Exogenous application of Ca2+ resulted in successful
recovery of both primary and lateral root growth in osclp. Moreover,
overexpression of OsCLP resulted in improved growth with modified seed shape and
starch structure; however, the overall yield remained unaffected. Taken together,
our results highlight the involvement of OsCLP in rice growth by regulating the
intracellular calcium concentrations.
PMID- 28401569
TI - Influences on viral replication and sensitivity to GLS4, a HAP compound, of
naturally occurring T109/V124 mutations in hepatitis B virus core protein.
AB - Heteroaryldihydropyrimidine (HAP) compounds inhibit HBV replication by binding to
a hydrophobic pocket at the interface between hepatitis B virus core protein
(HBcAg) dimer, which interrupts capsid assembly by changing the kinetics and
thermodynamics during this process. Structure biological studies have identified
several amino acids in HBcAg crucial for compound binding. Here, we investigated
the polymorphisms of T109 and V124 amino acids in HBV sequences submitted to
GenBank database. Naturally occurring T109 and V124 and/or possible compensatory
mutations in neighbored amino acids were introduced into HBV-expressing plasmids.
Viral replication competence and sensitivity to GLS4, a HAP compound, were
evaluated using transient transfection and in vitro infection cell models. All
tested mutations in these amino acids led to decreasing viral DNA replication at
different levels. Specially, T109N and all V124 mutants caused severe
deficiencies in viral plus-strand DNA synthesis. T109I single mutation and all
T109S/M/C/N mutations impaired HBeAg secretion. T109I showed modestly decreased
sensitivities with IC50 3.3- to 6.8-folds higher than wild-type virus. In vitro
infection assay showed T109N and all V124 mutants failed to synthesize cccDNA and
following viral proteins. The other mutants, however, produced functional cccDNA
pools as wild-type virus did. Taken together, we profiled the competences of
viral replication and sensitivities to capsid inhibitor of naturally existing
mutations in T109 and V124. This will help to understand the possible antiviral
resistance issues in future clinical applications of capsid inhibitors.
PMID- 28401570
TI - Effect of P-glycoprotein inhibition at the blood-brain barrier on brain
distribution of (R)-[11 C]verapamil in elderly vs. young subjects.
AB - AIMS: The efflux transporter P-glycoprotein (ABCB1) acts at the blood-brain
barrier (BBB) to restrict the distribution of many different drugs from blood to
the brain. Previous data suggest an age-associated decrease in the expression and
function of ABCB1 at the BBB. In the present study, we investigated the influence
of age on the magnitude of an ABCB1-mediated drug-drug interaction (DDI) at the
BBB. METHODS: We performed positron emission tomography scans using the model
ABCB1 substrate (R)-[11 C]verapamil in five young [26 +/- 1 years, (mean +/-
standard deviation)] and five elderly (68 +/- 6 years) healthy male volunteers
before and after intravenous administration of a low dose of the ABCB1 inhibitor
tariquidar (3 mg kg-1 ). RESULTS: In baseline scans, the total distribution
volume (VT ) of (R)-[11 C]verapamil in whole-brain grey matter was not
significantly different between the elderly (VT = 0.78 +/- 0.15) and young (VT
= 0.79 +/- 0.10) group. After partial (incomplete) ABCB1 inhibition, VT values
were significantly higher (P = 0.040) in the elderly (VT = 1.08 +/- 0.15) than
in the young (VT = 0.80 +/- 0.18) group. The percentage increase in (R)-[11
C]verapamil VT following partial ABCB1 inhibition was significantly greater (P =
0.032) in elderly (+40 +/- 17%) than in young (+2 +/- 17%) volunteers. Tariquidar
plasma concentrations were not significantly different between the young (786 +/-
178 nmol l-1 ) and elderly (1116 +/- 347 nmol l-1 ) group. CONCLUSIONS: Our
results provide the first direct evidence of an increased risk for ABCB1-mediated
DDIs at the BBB in elderly persons, which may have important consequences for
pharmacotherapy of the elderly.
PMID- 28401571
TI - Tying knots: an activity theory analysis of student learning goals in clinical
education.
AB - CONTEXT: Learning goal programmes are often created to help students develop self
regulated learning skills; however, these programmes do not necessarily consider
the social contexts surrounding learning goals or how they fit into daily
educational practice. OBJECTIVES: We investigated a high-frequency learning goal
programme in which students generated and shared weekly learning goals with their
clinical teams in core Year 3 clerkships. Our study explores: (i) how learning
goals were incorporated into the clinical work, and (ii) the factors that
influenced the use of students' learning goals in work-based learning. METHODS:
We conducted semi-structured interviews with 14 students and 14 supervisors
(attending physicians and residents) sampled from all participating core
clerkships. Interviews were coded for emerging themes. Using cultural historical
activity theory and knotworking as theoretical lenses, we developed a model of
the factors that influenced students' learning goal usage in a work-based
learning context. RESULTS: Students and supervisors often faced the challenge of
reconciling contradictions that arose when the desired outcomes of student skill
development, grading and patient care were not aligned. Learning goals could
function as tools for developing new ways of acting that overcame those
contradictions by facilitating collaborative effort between students and their
supervisors. However, for new collaborations to take place, both students and
supervisors had to engage with the goals, and the necessary patients needed to be
present. When any one part of the system did not converge around the learning
goals, the impact of the learning goals programme was limited. CONCLUSIONS:
Learning goals are potentially powerful tools to mediate interactions between
students, supervisors and patients, and to reconcile contradictions in work-based
learning environments. Learning goals provide a means to develop not only
learners, but also learning systems.
PMID- 28401572
TI - Morphological structures for potential sperm storage in poeciliid fishes. Does
superfetation matter?
AB - Sperm storage within the female reproductive tract has been reported as a
reproductive strategy in several species of vertebrates and invertebrates.
However, the morphological structures that allow for sperm to be stored and kept
viable for long periods are relatively unknown in osteichthyes. We use
histological and stereological tools to identify and quantify sperm storage
structures (spermathecae) in 12 species of viviparous Poeciliidae. We found
spermathecae in nine species, six of which exhibit superfetation (the ability of
females to simultaneously carry within the ovary two or more broods of embryos at
different stages of development). These spermathecae are folds of ovarian tissue
that close around spermatozoa. We compared the number and size (volume) of
spermathecae between species with and without superfetation. Species that exhibit
superfetation had a significantly higher number of spermathecae than species that
do not exhibit this reproductive strategy. In addition, we found that the mean
volume of spermathecae and total volume of spermathecae present in the ovary are
marginally higher in species with superfetation. Our results contribute to the
understanding of the morphological structures that allow for sperm storage in
viviparous osteichthyes and suggest a positive relationship between superfetation
and the capacity of females to store sperm.
PMID- 28401573
TI - Is tocilizumab a potential therapeutic option for refractory unicentric Castleman
disease?
AB - Castleman disease is a rare lymphoproliferative disorder with 2 distinctly
defined clinical forms. While multicentric Castleman disease (UCD) poses a
potential therapeutic challenge, unicentric variant has historically been
considered curable with surgical resection. Hence, little is known to guide
management of patients with UCD, refractory to surgical resection and combination
chemotherapy. We present a case of a patient, negative for HIV and HHV-8, who had
an unsuccessful surgical intervention and no response to radiotherapy and
chemotherapy. He had severe paraneoplastic pemphigus and was treated with
tocilizumab, an anti-interleukin-6 receptor monoclonal antibody that has
demonstrated good response rates in multicentric Castleman disease but
demonstrated no clinical response despite 2 months of treatment. Our report is
the first to describe a lack of response to tocilizumab in the rare setting of
refractory UCD and discuss potential for distinct disease biology.
PMID- 28401574
TI - Complete metabolic response (CMR) in positron emission tomography-computed
tomography (PET-CT) scans may have prognostic significance in patients with
marginal zone lymphomas (MZL).
AB - Although clinical use of positron emission tomography-computed tomography (PET
CT) scans is well established in aggressive lymphomas, its prognostic value in
marginal zone lymphoma (MZL) remains yet unclear. Hence, we investigated
potential role of PET-CT in predicting MZL patients' outcomes following systemic
chemotherapy. A total of 32 patients with MZL who received first-line
chemotherapy were included in the analysis. They all underwent pretreatment,
interim, and posttreatment PET-CT scans. The primary objective was to evaluate
the role of complete metabolic response (CMR) in posttreatment PET-CT scans in
predicting progression-free survival (PFS). Compared with non-CMR group, 5-year
PFS rate was significantly higher in patients who achieved CMR in posttreatment
PET-CT (54.2% vs 0.0%, P = .003) and also in patients gaining CMR in interim PET
CT scans (62.5% vs 15.6%, P = .026). Interestingly, early CMR group, who achieved
and maintained CMR in both interim and posttreatment PET-CT scans, showed
significantly higher 5-year PFS than those with delayed or never CMR group (62.5%
vs 37.5% vs 0%, P = .008). Therefore, interim and/or posttreatment CMR can be
prognostic at least in these subsets of patients with MZL treated with
chemotherapy.
PMID- 28401575
TI - New Insights into the Neural Differentiation Potential of Canine Adipose Tissue
Derived Mesenchymal Stem Cells.
AB - Adipose tissue-derived stem cells (ASCs) can be obtained from different adipose
tissue sources within the body. It is an abundant cell pool, easily accessible,
suitable for cultivation and expansion in vitro and preparation for therapeutic
approaches. Amongst these therapeutic approaches are tissue engineering and
nervous system disorders such as spinal cord injuries. For such treatment, ASCs
have to be reliably differentiated in to the neuronal direction. Therefore, we
investigated the neural differentiation potential of ASCs using protocols with
neurogenic inductors such as valproic acid and forskolin, while dog brain tissue
served as control. Morphological changes could already be noticed 1 h after
neuronal induction. Gene expression analysis revealed that the neuronal markers
nestin and betaIII-tubulin as well as MAP2 were expressed after induction of
neuronal differentiation. Additionally, the expression of the neurotrophic
factors NGF, BDNF and GDNF was determined. Some of the neuronal markers and
neurotrophic factors were already expressed in undifferentiated cells. Our
findings point out that ASCs can reliably be differentiated into the neuronal
lineage; therefore, these cells are a suitable cell source for cell
transplantation in disorders of the central nervous system. Follow-up studies
would show the clinical benefit of these cells after transplantation.
PMID- 28401577
TI - A Brief Report on the Ethical and Legal Guides For Technology Use in Marriage and
Family Therapy.
AB - Marriage and family therapists (MFTs) use ethical codes and state licensure
laws/rules as guidelines for best clinical practice. It is important that
professional codes reflect the potential exponential use of technology in
therapy. However, current standards regarding technology use lack clarity. To
explore this gap, a summative content analysis was conducted on state licensure
laws/rules and professional ethical codes to find themes and subthemes among the
many aspects of therapy in which technology can be utilized. Findings from the
content analysis indicated that while there have been efforts by both state and
professional organizations to incorporate guidance for technology use in therapy,
a clear and comprehensive "roadmap" is still missing. Future scholarship is
needed that develops clearer guidelines for therapists.
PMID- 28401576
TI - A new nomenclature for classifying psychotropic drugs.
AB - The Neuroscience-based Nomenclature (NbN) for psychotropic drugs was developed as
an alternative to the current Anatomical Therapeutic Chemical (ATC) indication
based classification in order to provide more precise designations for this drug
class. The ATC nomenclature for psychotherapeutics is limited in that it fails to
specify either pharmacological domains or mechanism of action and also does not
describe all the potential uses of a particular agent. The disconnect between the
drug classification and its clinical use is not very useful for scientific
purposes and is confusing for patients and caregivers, often leading to a
misunderstanding of the intended effects of the prescribed medication and, most
importantly, to low treatment adherence. The NbN classifies psychopharmacological
agents on the basis of contemporary scientific information on their pharmacology
and mechanisms of action so as to provide physicians clear alternatives when
selecting or altering therapeutic regimens. The classification of each
psychotropic drug includes four additional dimensions: approved indications;
efficacy and side effects; practical note; neurobiology. By emphasizing the
pharmacology and the molecular mechanism of action, NbN provides a vehicle for
clinicians and basic scientists to improve the understanding and clinical use of
this important drug class.
PMID- 28401578
TI - Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent
model with high serum testosterone: Protective effect and emergence of unstable
epithelial microenvironment.
AB - BACKGROUND: Estrogens are critical players in prostate growth and disease.
Estrogen therapy has been the standard treatment for advanced prostate cancer for
several decades; however, it has currently been replaced by alternative anti
androgenic therapies. Additionally, studies of its action on prostate biology,
resulting from an association between carcinogens and estrogen, at different
stages of life are scarce or inconclusive about its protective and beneficial
role on induced-carcinogenesis. Thus, the aim of this study was to determine
whether estradiol exerts a protective and/or stimulatory role on N-methyl-N
nitrosurea-induced prostate neoplasms. METHODS: We adopted a rodent model that
has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We
investigated the occurrence of neoplasms, karyometric patterns, androgen and
estrogen receptors, basal cells, and global methylation status in ventral and
dorsolateral prostate tissues. RESULTS: Histopathological analysis showed that
estrogen was able to slow tumor growth in both lobes after prolonged treatment.
However, a true neoplastic regression was observed only in the dorsolateral
prostate. In addition to the protective effects against neoplastic progression,
estrogen treatment resulted in an epithelium that exhibited features distinctive
from a normal prostate, including increased androgen-insensitive basal cells,
high androgens and estrogen receptor positivity, and changes in DNA methylation
patterns. CONCLUSIONS: Estrogen was able to slow tumor growth, but the epithelium
exhibited features distinct from a normal prostatic epithelium, and this unstable
microenvironment could trigger lesion recurrence over time.
PMID- 28401579
TI - MRI assessment of tissue effects after 180-W XPS greenlight laser vaporization of
the prostate.
AB - BACKGROUND AND OBJECTIVE: Photoselective vaporization of the prostate (PVP) is an
alternative to transurethral resection of the prostate (TURP) in the surgical
management of Benign Prostate Obtruction (BPO), with a better hemostatic effect
due to a coagulation depth of several millimeters. The objective of this study
was to prospectively assess the tissue effects of PVP by Magnetic Resonance
Imaging (MRI). MATERIALS AND METHODS: From December to February 2014, ten
patients were included in a prospective study and underwent PVP performed by a
single surgeon with the GreenlightTM laser 180-W XPS. A multiparametric MRI of
the prostate (Siemens 3T Verio) was achieved the day before the procedure and
post-operatively (2 days, 7 days, 3 and 6 months after the procedure). The
prostate volume after tissue removal was determined. The depth of necrosis in the
prostatic and peri-prostatic tissues were assessed at six different locations.
RESULTS: The median age and pre-operative prostate volume were 70 years (64-76)
and 48.1 ml (19-74.4), respectively. Median prostate volume significantly
decreased post-operatively (P < 0.001): At 6 months, median prostate volume
reduction was 44.2% (38.7-49.5) (P = 0.001) compared to pre-operative setting.
Two and 7 days after the procedure, mean depths of necrosis were 2.5 mm (0-3) and
1.3 mm (0-2.4), respectively. No necrosis was reported 3 and 6 months after the
procedure. CONCLUSIONS: PVP with GreenlightTM XPS 180-W is associated with a
significant reduction of prostate volume. The depth of necrosis is low and
homogeneous, resulting in a limited risk of peri-operative complications. Lasers
Surg. Med. 49:577-581, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401580
TI - Military sexual trauma is associated with post-deployment eating disorders among
Afghanistan and Iraq veterans.
AB - OBJECTIVE: Evaluate the association of military sexual trauma (MST) screen status
with eating disorder diagnoses among veterans within 1- and 5-years after
initiating Veterans Health Administration (VHA) care, and whether the association
varied by sex. METHOD: Retrospective cohort study of US Afghanistan/Iraq veterans
who used VHA services between FY 2004 and 2014 (N = 595,525). This study used VHA
administrative data to assess the presence of eating disorder diagnoses in
medical records within 1- and 5-years of initiating VHA care, and whether a
positive screen for MST was associated with eating disorders. RESULTS: Three
percent (n = 18,488) screened positive for MST. At 1- and 5-year follow up, 0.1%
(n= 513, 74% female), and 0.2% (n = 504, 71% female) were diagnosed with an
eating disorder, respectively. In regression models adjusted for demographic
variables, military service, and psychiatric comorbidities, the presence of an
eating disorder diagnosis was nearly two times higher among those with a positive
screen for MST in the 1-year (adjusted odds ratio [AOR] = 1.94, 95% confidence
interval [CI] = 1.57-2.40) and 5-year (AOR = 1.86, 95%CI = 1.49-2.32) cohorts.
The increased likelihood conferred by MST for an eating disorder diagnosis was
differentially stronger among male veterans than female veterans in the 1-year
cohort only (AOR = 2.13, 95%CI = 1.01-4.50). DISCUSSION: Veterans with a positive
screen for MST, especially male veterans, had a nearly two-fold increased
likelihood of having an eating disorder diagnosis. Screening for eating disorders
may be important in both male and female veterans who report MST.
PMID- 28401581
TI - Seborrheic keratosis with basal clear cells: Report of a case and review of the
literature.
PMID- 28401582
TI - Histological features of malignancy correlate with growth patterns and patient
outcome in lung adenocarcinoma.
AB - AIMS: Until the launch of the International Association for the Study of Lung
Cancer/American Thoracic Society/European Respiratory Society adenocarcinoma
classification in 2011, there were no uniform histological grading criteria for
pulmonary adenocarcinomas. The current classification highlights the prognostic
importance of the various histological growth patterns observed in these
morphologically heterogeneous neoplasias. In this study, we aimed to evaluate the
classic histological parameters of malignancy in correlation with the growth
patterns and patient outcomes in a series of 112 surgically operated stage I-IV
lung adenocarcinomas. METHODS AND RESULTS: Architectural growth pattern analysis
was performed according to the current adenocarcinoma classification.
Histological features including, for example, nuclear atypia, mitotic activity,
tumour necrosis, and different patterns of invasion were assessed and correlated
statistically with the architecture and the clinical data. A solid predominant
histology was associated with increased levels of atypia (P = 0.027), mitotic
activity (P < 0.001), necrosis (P < 0.001), and lymphovascular invasion (P =
0.001), and a non-predominant solid pattern was associated with intra-alveolar
tumour spread (P = 0.004). The presence of a non-predominant lepidic tumour
component showed inverse correlations with atypia (P = 0.002), mitotic rate (P =
0.009), and tumour necrosis (P < 0.001). Tumour size (P < 0.001), mitotic
activity (P = 0.019), tumour necrosis (P = 0.002), lymphovascular invasion (P =
0.001) and visceral pleural involvement (P = 0.001) were all associated with
reduced disease-specific survival. CONCLUSIONS: The classic histological features
of malignancy correlate with tumour architecture and patient outcome, confirming
the prognostic value of the growth pattern analysis and questioning the need for
a parallel grading system in pulmonary adenocarcinoma.
PMID- 28401584
TI - Psychodynamic Couple Therapy: A Practical Synthesis.
AB - This essay reviews the most significant contributions of psychodynamic thought to
the field of couple therapy. It distills the work of numerous clinicians and
researchers who, though writing from diverse perspectives, share fundamental
assumptions and concerns. Rather than emphasizing differences between schools of
thought, this paper mines their best contributions in a discussion of five
central therapeutic targets: underlying issues, divergent subjective experiences,
transferences, projective identification, and acceptance. Two detailed cases
illustrate the benefits and techniques for targeting these five therapeutic
domains. Video Abstract is found in the online version of the article.
PMID- 28401583
TI - Informal care: choice or constraint?
AB - BACKGROUND: 'Choice' is increasingly pursued as a goal of social policy. However,
the degree to which choice is exercised when entering an informal caring role is
open to debate. AIM: In this study, we examined the degree of choice and
constraint in entering a caring role, and the relationship between choice and
carers' well-being. METHODS: Data were derived from 1100 responses to a postal
survey conducted in a British city. Statistical tests of association and
multivariable regression modelling were applied to study the factors associated
with choice in entering a caring role and the association that choice in entering
a caring role had with carers' well-being. RESULTS: We found that informal care
was generally perceived to be a free choice, albeit in most cases, a choice was
also constrained by duty, financial or social resources. Having a sense of free
choice in entering care was strongly and positively associated with the carer's
well-being. CONCLUSION: The study findings are consistent with a view that
enabling individuals to have more choice in their caring roles may be beneficial.
PMID- 28401585
TI - A proposed scoring system for assessing the severity of actinic keratosis on the
head: actinic keratosis area and severity index.
AB - BACKGROUND: Actinic keratosis (AK) severity is currently evaluated by subjective
assessment of patients. OBJECTIVES: To develop and perform an initial pilot
validation of a new easy-to-use quantitative tool for assessing AK severity on
the head. METHODS: The actinic keratosis area and severity index (AKASI) for the
head was developed based on a review of other severity scoring systems in
dermatology, in particular the psoriasis area and severity index (PASI). Initial
validation was performed by 13 physicians assessing AK severity in 18 AK patients
and two controls using a physician global assessment (PGA) and AKASI. To
determine an AKASI score, the head was divided into four regions (scalp,
forehead, left/right cheek ear, chin and nose). In each region, the percentage of
the area affected by AKs was estimated, and the severities of three clinical
signs of AK were assessed: distribution, erythema and thickness. RESULTS: There
was a strong correlation between AKASI and PGA scores (Pearson correlation
coefficient: 0.86). AKASI was able to discriminate between different PGA
categories: mean (SD) AKASI increased from 2.88 (1.18) for 'light' to 5.33 (1.48)
for 'moderate', 8.28 (1.89) for 'severe', and 8.73 (3.03) for 'very severe' PGA
classification. The coefficient of variation for AKASI scores was low and
relatively constant across all PGA categories. CONCLUSIONS: Actinic keratosis
area and severity index is proposed as a new quantitative tool for assessing AK
severity on the head. It may be useful in the future evaluation of new AK
treatments in clinical studies and the management of AK in daily practice.
PMID- 28401586
TI - Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy.
AB - Climatic droplet keratopathy (CDK) is an acquired degenerative disease
predominantly affecting males over 40 years old. It results in progressive
corneal opacities usually affecting both eyes. CDK is multifactorial and its
etiology remains unknown. Our recent findings are consistent with CDK pathology
being driven by environmental factors with oxidative stress playing an important
role (e.g.,, contributing to lipid peroxidation) rather than climate factors. The
changes in corneal lipid composition affected by environmental factors remain
understudied. The purpose of this study was to systematically investigate
phospholipids profile (phosphatidylcholine [PC] and phosphatidylserine [PS]) in
corneas from CDK patients using tandem mass spectrometry. Samples from CDK areas
and from non-affected areas were obtained from patients diagnosed with CDK who
underwent cataract surgery, were subjected to lipid extraction using a modified
Bligh and Dyer method; protein concentrations were determined using the
Bradford's method. Lipids were identified and subjected to ratiometric
quantification using TSQ Quantum Access Max triple quadrupole mass spectrometer,
using appropriate class specific lipid standards. All phospholipid classes showed
lower total amounts in affected areas compared to control areas from CDK's
corneas. Comparative profiles of two phospholipid classes (PC, PS) between CDK
areas and control areas showed several common species between them. We also found
a few unique lipids that were absent in CDK areas compared to controls and vice
versa. Lower amount of phospholipids in CDK areas compared to control areas could
be attributed to the lipid peroxidation in the affected corneal regions as a
consequence of increased oxidative stress. J. Cell. Biochem. 118: 3920-3931,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401588
TI - Tri-s-triazine-Based Crystalline Carbon Nitride Nanosheets for an Improved
Hydrogen Evolution.
AB - Tri-s-triazine-based crystalline carbon nitride nanosheets (CCNNSs) have been
successfully extracted via a conventional and cost-effective sonication
centrifugation process. These CCNNSs possess a highly defined and unambiguous
structure with minimal thickness, large aspect ratios, homogeneous tri-s-triazine
based units, and high crystallinity. These tri-s-triazine-based CCNNSs show
significantly enhanced photocatalytic hydrogen generation activity under visible
light than g-C3 N4 , poly (triazine imide)/Li+ Cl- , and bulk tri-s-triazine
based crystalline carbon nitrides. A highly apparent quantum efficiency of 8.57%
at 420 nm for hydrogen production from aqueous methanol feedstock can be achieved
from tri-s-triazine-based CCNNSs, exceeding most of the reported carbon nitride
nanosheets. Benefiting from the inherent structure of 2D crystals, the ultrathin
tri-s-triazine-based CCNNSs provide a broad range of application prospects in the
fields of bioimaging, and energy storage and conversion.
PMID- 28401587
TI - Valuation of Life as outcome and mediator of a depression intervention for older
African Americans: the Get Busy Get Better Trial.
AB - OBJECTIVE: Previously, we showed that Get Busy Get Better (GBGB), a 10-session
multicomponent home-based, behavioral intervention, reduced depressive symptom
severity in older African Americans. As appraising the value of life is
associated with depressive symptoms, this study examined whether GBGB enhanced
positive appraisals of life and if, in turn, this mediated treatment effects on
depressive symptoms. METHODS: Data were from a single-blind parallel randomized
trial involving 208 African Americans (>=55 years old) with depressive symptoms
(Patient Health Questionnaire, PHQ-9 >=5). GBGB involved five components: care
management, referral/linkage, stress reduction, depression education, and
behavioral activation. A 13-item Valuation of Life (VOL) scale with two
subfactors (optimism and engagement) was examined as an outcome and as mediating
GBGB effects on PHQ-9 scores at 4 months. RESULTS: Of 208 enrolled African
Americans, 180 completed the 4-month interview (87 = GBGB; 93 = control). At 4
months, compared with wait-list control group participants, the GBGB group had
improved VOL (difference in mean changes from baseline = 4.67, 95% confidence
interval 2.53, 6.80). Structural equation models indicated that enhanced VOL
mediated a significant proportion of GBGB's impact on depressive symptoms,
explaining 71% of its total effect, and its subfactors (optimism, explaining 67%;
engagement, 52%). CONCLUSION: Valuation of Life appears malleable through an
intervention providing resources and activation skills. GBGB's impact on
depressive symptoms is attributed in large part to participants' enhanced
attachment to life. Attention to VOL as mediator and outcome and the reciprocal
relationship between mood and attachment to life is warranted. Copyright (c) 2017
John Wiley & Sons, Ltd.
PMID- 28401589
TI - Rhodoid naevus syndrome: why is this name preferable to 'capillary malformation
arteriovenous malformation'?
PMID- 28401590
TI - Self-Organized Epitaxial Vertically Aligned Nanocomposites with Long-Range
Ordering Enabled by Substrate Nanotemplating.
AB - Vertically aligned nanocomposites (VAN) thin films present as an intriguing
material family for achieving novel functionalities. However, most of the VAN
structures tend to grow in a random fashion, hindering the future integration in
nanoscale devices. Previous efforts for achieving ordered nanopillar structures
have been focused on specific systems, and rely on sophisticated lithography and
seeding techniques, making large area ordering quite difficult. In this work, a
new technique is presented to produce self-assembled nanocomposites with long
range ordering through selective nucleation of nanocomposites on termination
patterned substrates. Specifically, SrTiO3 (001) substrates have been annealed to
achieve alternating chemical terminations and thus enable selective epitaxy
during the VAN growth. La0.7 Sr0.3 MnO3 :CeO2 (LSMO):CeO2 nanocomposites, as a
prototype, are demonstrated to form well-ordered rows in matrix structure, with
CeO2 (011) domains selectively grown on SrO terminated area, showing enhanced
functionality. This approach provides a large degree of long-range ordering for
nanocomposite growth that could lead to unique functionalities and takes the
nanocomposites one step closer toward future nanoscale device integration.
PMID- 28401591
TI - Dynamics of BKPyV reactivation and risk of hemorrhagic cystitis after allogeneic
hematopoietic stem cell transplantation.
AB - OBJECTIVES: Aim of this retrospective study was to analyze the dynamics of BKPyV
reactivation in allogeneic hematopoietic stem cell transplant recipients in order
to identify patients with higher risk to develop BKPyV-associated hemorrhagic
cystitis (BKPyV-associated HC). METHODS: The study included 58 allo-HSCT
recipients from the University Hospital of Cologne detected BKPyV positive by
real-time PCR between 2009 and 2015. For correlative analysis, the first detected
BKPyV-DNA load in urine and in plasma as well as the onset and severity of HC
following the first day of conditioning regimen was considered. Phylogenetic
analysis of BKPyV isolates was performed. RESULTS: In 25 of 58 patients, BKPyV
DNA was detected in urine only (group U), whereas 33 patients developed
additional viremia (group P). A chronologic sequence viruria-viremia-HC was
identified. Viral load of >106 copies/mL at first viruria and evidence of viremia
after 45 days from the start of conditioning represented risk factors for the
onset of HC. Molecular characterization revealed a non-stereotypic distribution
of viral subtypes across groups U and P. CONCLUSIONS: Monitoring of BKPyV-DNA by
real-time PCR after initiation of conditioning, regularly performed in clinical
practice, can be a crucial tool for the early identification of patients with
higher risk of BKPyV-associated HC.
PMID- 28401592
TI - A Niccolite Structural Multiferroic Metal-Organic Framework Possessing Four
Different Types of Bistability in Response to Dielectric and Magnetic Modulation.
AB - Multiple switchable physical properties have been demonstrated in one single
niccolite structural metal-organic framework, [(CH3 CH2 )2 NH2 ][FeIII FeII
(HCOO)6 ] (1), including (i) a reversible ferroelastic phase transition triggered
by freezing the disordered (CH3 CH2 )2 NH2+ cations, (ii) a thermally switchable
dielectric constant transition accompanied by phase transition, and (iii) thermal
and positive magnetic field driven magnetic poles reversal at low temperatures,
attributed to different responses of the magnetization of FeII and FeIII
sublattices to external stimuli. More interestingly, the exchange anisotropy
between the two sublattices can also give rise to tunable positive and negative
exchange bias fields. Straightforwardly, such diverse demonstrations of
bistability in one single material (depending on the specific tuning way) will
provide extra freedom and flexibility for the design of switcher devices.
PMID- 28401593
TI - Low-dose BMP-2 and MSC dual delivery onto coral scaffold for critical-size bone
defect regeneration in sheep.
AB - Tissue-engineered constructs (TECs) combining resorbable calcium-based scaffolds
and mesenchymal stem cells (MSCs) have the capability to regenerate large bone
defects. Inconsistent results have, however, been observed, with a lack of
osteoinductivity as a possible cause of failure. This study aimed to evaluate the
impact of the addition of low-dose bone morphogenetic protein-2 (BMP-2) to MSC
coral-TECs on the healing of clinically relevant segmental bone defects in sheep.
Coral granules were either seeded with autologous MSCs (bone marrow-derived) or
loaded with BMP-2. A 25-mm-long metatarsal bone defect was created and stabilized
with a plate in 18 sheep. Defects were filled with one of the following TECs: (i)
BMP (n = 5); (ii) MSC (n = 7); or (iii) MSC-BMP (n = 6). Radiographic follow-up
was performed until animal sacrifice at 4 months. Bone formation and scaffold
resorption were assessed by micro-CT and histological analysis. Bone union with
nearly complete scaffold resorption was observed in 1/5, 2/7, and 3/6 animals,
when BMP-, MSC-, and MSC-BMP-TECs were implanted, respectively. The amount of
newly formed bone was not statistically different between groups: 1074 mm3 [970
2478 mm3 ], 1155 mm3 [970-2595 mm3 ], and 2343 mm3 [931-3276 mm3 ] for BMP-, MSC
, and MSC-BMP-TECs, respectively. Increased scaffold resorption rate using BMP
TECs was the only potential side effect observed. In conclusion, although the
dual delivery of MSCs and BMP-2 onto a coral scaffold further increased bone
formation and bone union when compared to single treatment, results were non
significant. Only 50% of the defects healed, demonstrating the need for further
refinement of this strategy before clinical use. (c) 2017 Orthopaedic Research
Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2637-2645, 2017.
PMID- 28401594
TI - Incidental tricuspid valve fibroelastoma associated with patent foramen ovale in
a young female: Straightforward diagnosis but controversial management.
AB - Papillary fibroelastoma is an uncommon primary cardiac tumor, predominantly
associated with left-sided valvular endocardium. Affectation of tricuspid valve
leaflets is rare, and management in asymptomatic patients remains controversial.
We present a 30-year-old female referred for evaluation prior to bariatric
surgery. A routine echocardiogram revealed a mobile cardiac mass attached to the
tricuspid valve. A patent foramen ovale was also present. Tumor was surgically
removed. Histology confirmed the definite diagnosis of a papillary fibroelastoma.
In our case, the presence of a patent foramen ovale associated with the right
sided fibroelastoma was decisive in the decision for surgery.
PMID- 28401595
TI - Assessing a cognitive music training for older participants: a randomised
controlled trial.
AB - OBJECTIVES: In a randomised controlled trial, we investigated whether a cognitive
training based on rhythm-music and music improvisation exercises had positive
effects on executive functions in older participants. METHODS: Thirty-five
residents in a guest home with mild-moderate cognitive impairment and healthy
ageing were randomly assigned to an experimental group (n = 18) featuring
cognitive music training composed of 12 bi-weekly 70-min sessions, and a control
group (n = 17) attended 12 bi-weekly 45-min sessions of gymnastic activities
offered by the institute. A neuropsychological test battery was administered at
baseline and at the end of treatment, including the Mini-Mental State
Examination, verbal fluency test, Trail Making Test A, attentional matrices test
and clock-drawing test. RESULTS: Pre-test and post-test comparison showed a
significant improvement for the experimental group reflected in the Mini-Mental
State Examination (F(1,33) = 13.906; p < 0.001; peta2 = 0.296), verbal fluency
test (VFL) (F(1,33) = 6.816; p < 0.013; peta2 = 0.171), and clock-drawing test
(F(1,29) = 16.744; p < 0.001; peta2 = 0.366), while the control group did not
show any significant improvements. In addition, there was a tendency towards
significance for the Trail Making Test A (F(1,20) = 3.268; p < 0.086; peta2 =
0.140). Regarding the attentional matrices test, no significant differences were
found for the experimental group (F(1,29) = 2.833; p < 0.103; peta2 = 0.089),
while the control group had a significant performance reduction (F(1,29) = 3.947;
p < 0.050; peta2 = 0.120). CONCLUSION: The use of a cognitive protocol based on
music-rhythmic exercises and music improvisation exercises is associated with
improved cognitive functions in older people with mild-moderate cognitive
impairment regardless of the individual's degree of cognitive reserve. Copyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28401596
TI - Successful retreatment with combined BRAF/MEK inhibition in metastatic BRAFV600
mutated melanoma.
AB - BACKGROUND: The combination treatment with BRAF and MEK inhibitors is amongst the
current standard of care for stage IIIC/IV BRAF-mutated melanoma. However,
therapeutic options are limited once patients have progressed upon both targeted
and immunotherapy. OBJECTIVE: To investigate whether retreatment with BRAF and
MEK inhibitor combination is an option for patients with metastatic BRAF-mutated
melanoma upon previous progression on kinase inhibitors. METHODS: Two patients
with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK
inhibitor combination after progression on targeted therapy and subsequent
immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies. RESULTS: Both patients
responded to retreatment. Responses were limited to a few months and associated
with a considerable increase in quality of life. CONCLUSION: Retreatment with
BRAF and MEK inhibitors may present a feasible treatment option upon progression
on both kinase inhibitors and immunotherapy, and should be considered when all
other treatment options have been exhausted.
PMID- 28401597
TI - Unidirectional Wetting Properties on Multi-Bioinspired Magnetocontrollable
Slippery Microcilia.
AB - Here, a smart fluid-controlled surface is designed, via the rational integration
of the unique properties of three natural examples, i.e., the unidirectional
wetting behaviors of butterfly's wing, liquid-infused "slippery" surface of the
pitcher plant, and the motile microcilia of micro-organisms. Anisotropic
wettability, lubricated surfaces, and magnetoresponsive microstructures are
assembled into one unified system. The as-prepared surface covered by tilted
microcilia achieves significant unidirectional droplet adhesion and sliding.
Regulating by external magnet field, the directionality of ferromagnetic
microcilia can be synergistically switched, which facilitates a continuous and
omnidirectional-controllable water delivery. This work opens an avenue for
applications of anisotropic wetting surfaces, such as complex-flow distribution
and liquid delivery, and extend the design approach of multi-bioinspiration
integration.
PMID- 28401598
TI - Dcf1 Improves Behavior Deficit in Drosophila and Mice Caused by Optogenetic
Suppression.
AB - Optogenetics play a significant role in neuroscientific research by providing a
tool for understanding neural circuits and brain functions. Natronomonas
pharaonis halorhodopsin (NpHR) actively pumps chloride ions into the cells and
hyperpolarizes neuronal membranes in response to yellow light. In this study, we
generated transgenic Drosophila expressing NpHR under the control of the Gal4/UAS
system and virus-infected mice expressing NpHR to explore the effect of dendritic
cell factor 1 (Dcf1) on the behavior mediated by the mushroom body in Drosophila
and the dentate gyrus (DG) in mice. Study of optogenetic behavior showed that
NpHR suppressed the behavior in Drosophila larvae and mice, whereas Dcf1 rescued
this suppression. These results suggest that Dcf1 plays an important role in
behavior induced by the mushroom body and the hippocampus and provides novel
insights into their functions. J. Cell. Biochem. 118: 4210-4215, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28401599
TI - FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell
Proliferation Advantage.
AB - FOXM1 transcription factor is a central component of tumor initiation, growth,
and progression due to its multiple effects on cell cycle, DNA repair,
angiogenesis and invasion, chromatin, protein anabolism, and cell adhesion.
Moreover, FOXM1 interacts with beta-catenin promoting its nuclear import and
transcriptional activation. Here, we show that FOXM1 is involved in the advantage
of chronic myeloid leukemia hematopoiesis over the normal counterpart. FOXM1
hyper-activation associated with BCR-ABL1 results from phosphorylation by the
fusion protein kinase-dependent activation of Polo-like kinase 1. FOXM1
phosphorylation lets its binding with beta-catenin and beta-catenin
transcriptional activation, a key event for persistence of the leukemic stem cell
compartment under tyrosine kinase inhibitor therapy. Polo-like kinase 1 inhibitor
BI6727, already advanced for clinical use, breaks beta-catenin interaction with
FOXM1, hence hampering FOXM1 phosphorylation, beta-catenin binding, nuclear
import, and downstream signaling. In conclusion, our results support Polo-like
kinase 1/FOXM1 axis as a complementary target to eradicate leukemic early
progenitor/stem cell compartment in chronic myeloid leukemia. J. Cell. Biochem.
118: 3968-3975, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401600
TI - Involvement of patients' perspectives on treatment with noninvasive ventilation
in patients with chronic obstructive pulmonary disease-A qualitative study.
AB - AIMS AND OBJECTIVES: To clarify chronic obstructive pulmonary disease patients'
perspectives on treatment with noninvasive ventilation and develop management
strategies for the treatment based on these perspectives. BACKGROUND: The effect
of treating chronic obstructive pulmonary disease patients with noninvasive
ventilation is well-documented, as is the problem of patient difficulties in
tolerating the treatment. Knowledge of how patients with chronic obstructive
pulmonary disease experience and evaluate treatment with noninvasive ventilation
is limited; therefore, more information of patient perspectives is needed to
develop treatment practices in respiratory medicine. METHOD: This study is based
on critical psychological practice research. DESIGN: A co-researcher group
comprising diverse health professionals was set up and headed by the principal
researcher. The group convened seven times over 12 months to develop new
management strategies based on patients' perspectives on noninvasive ventilation.
Health professionals contributed with experience-based perspectives, and the
researcher contributed with data from participant observation in the department
and semi-structured interviews with 16 patients and four relatives. RESULTS:
Interviews revealed that patients with chronic obstructive pulmonary disease
regarded noninvasive ventilation treatment positively even though they
experienced discomfort and anxiety. Patients' perspectives revealed that patients
with chronic obstructive pulmonary disease conduct their everyday lives with
chronic obstructive pulmonary disease looking at chronic obstructive pulmonary
disease as a basic life condition rather than an illness. This approach had a
major impact on chronic obstructive pulmonary disease patients' attitudes to
noninvasive ventilation treatment and hospitalisation. CONCLUSION: Investigation
of patient perspectives generated results that were highly productive in
facilitating multidisciplinary collaboration and in developing and sustaining new
management strategies. Critical psychological practice research facilitated
ongoing development of clinical practice related to noninvasive ventilation
treatment. RELEVANCE TO CLINICAL PRACTICE: Focus on patients' perspectives in
treatment with noninvasive ventilation resulted in the development of new
management strategies regarding patient care, joint ward rounds, and in addition,
one room at the ward, to which a nurse was assigned, was designated for chronic
obstructive pulmonary disease patients treated with noninvasive ventilation.
PMID- 28401601
TI - Combinations of common polymorphisms within GSTA1 and GSTT1 as a risk factor for
psoriasis in a central European population: a case-control study.
PMID- 28401602
TI - Piloting a new patient-related outcome tool to assess cosmetic outcome in Mohs
Micrographic surgery.
PMID- 28401604
TI - Abstracts of the 18th Annual NATA Symposium on Patient Blood Management,
Haemostasis and Thrombosis, April 20-21, 2017, Florence, Italy.
PMID- 28401603
TI - Few-Layer Black Phosphorus Carbide Field-Effect Transistor via Carbon Doping.
AB - Black phosphorus carbide (b-PC) is a new family of layered semiconducting
material that has recently been predicted to have the lightest electrons and
holes among all known 2D semiconductors, yielding a p-type mobility (~105 cm2 V-1
s-1 ) at room temperature that is approximately five times larger than the
maximum value in black phosphorus. Here, a high-performance composite few-layer b
PC field-effect transistor fabricated via a novel carbon doping technique which
achieved a high hole mobility of 1995 cm2 V-1 s-1 at room temperature is
reported. The absorption spectrum of this material covers an electromagnetic
spectrum in the infrared regime not served by black phosphorus and is useful for
range finding applications as the earth atmosphere has good transparency in this
spectral range. Additionally, a low contact resistance of 289 Omega um is
achieved using a nickel phosphide alloy contact with an edge contacted interface
via sputtering and thermal treatment.
PMID- 28401606
TI - Transcriptional polymorphism of piRNA regulatory genes underlies the mariner
activity in Drosophila simulans testes.
AB - During colonization of new areas, natural populations have to deal with changing
environments, and transposable elements (TEs) can be useful "tools" in the
adaptation process as they are major contributor to the structural and functional
evolution of genomes. In this general context, the activity (copy number,
transcriptional and excision rate) of the mariner mos1 element was estimated in
19 natural populations of D. simulans. It is shown (i) that mos1 expression is
always higher and more variable in testes than in ovaries; (ii) that mos1
activity is higher in colonizing populations compared to the sub-Saharan African
ones (ancestral populations); (iii) that mos1 variations in transcript levels and
copy number are negatively correlated with transcriptional variations of piRNA
genes, aubergine and argonaute3. Furthermore, mos1 levels of expression in testes
highly contrast with the low expression patterns of ago3. These results strongly
suggest that the expression polymorphism of piRNA genes could be responsible for
the mos1 variations, first between male and female germlines and second,
according to the status of natural populations (colonizing or not). These results
provide new perspectives about TEs and piRNA genes co-evolution in Drosophila
germlines.
PMID- 28401605
TI - Predicting delivery of a small-for-gestational-age infant and adverse perinatal
outcome in women with suspected pre-eclampsia.
AB - OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound
parameters for the prediction of delivery of a small-for-gestational-age (SGA)
infant and adverse perinatal outcome in women presenting with suspected pre
eclampsia. METHODS: This was a prospective, multicenter observational study in
which 47 biomarkers and ultrasound parameters were measured in 397 women with a
singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 +
0 and 36 + 6 weeks' gestation, with the objective of evaluating them as
predictors of subsequent delivery of a SGA infant and adverse perinatal outcome.
Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis
and stepwise logistic regression were performed in two prespecified groups
stratified according to gestational age at enrollment. The primary outcome was
delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3),
and secondary outcomes were a SGA infant with a birth weight < 10th customized
centile and adverse perinatal outcome. RESULTS: In 274 women presenting at 20 + 0
to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of
SGA-3, low maternal placental growth factor (PlGF) concentration had a
sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90%
(95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of
79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or
abdominal circumference < 10th centile). No individual biomarker evaluated had a
better performance than did PlGF, and marker combinations made only small
improvements to the test performance. Similar results were found in 123 women
presenting between 35 + 0 and 36 + 6 weeks' gestation. CONCLUSION: In women
presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a
useful adjunct for identifying those at high risk of delivering a SGA infant,
allowing appropriate surveillance and timely intervention. (c) 2017 The Authors.
Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on
behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
PMID- 28401607
TI - 'It's like a drink you'd have before you go to a party': Analysis of a Vodka
Cruiser advertising campaign.
AB - INTRODUCTION AND AIMS: The aim of the present study was to explore young women's
understandings of, and interactions with, an advertising campaign for a pre-mixed
alcohol product that appeared to be promoting pre-drinking. This campaign was the
subject of complaints to the Alcohol Advertising Review Board, revealing an
inconsistency between the way the company responded to such complaints (arguing
that the campaign does not encourage pre-drinking) and the way it described the
campaign in trade press (the pre-drink enjoyed by the 'girls' while getting ready
...). DESIGN AND METHODS: Twelve focus groups were conducted with 72 young women,
aged 15-25 years in Melbourne, Australia. These young women's interpretations of
the messages communicated in this advertising campaign were analysed
thematically. RESULTS: The young women identified, without prompting, the main
message of the campaign as being a reference to pre-drinking. Most notably, the
women saw the target audience as young (including underage) women. DISCUSSION AND
CONCLUSIONS: Given that young women who drink are increasingly doing so at
harmful levels, a marketing campaign, which is interpreted by the target audience
to encourage pre-drinking among young (including underage) women, appears to be
inconsistent with the industry's own code for alcohol advertising. We renew the
call for effective regulation of alcohol advertising to better protect young
Australians. [Jones SC, Francis KL, Gordon CS. 'It's like a drink you'd have
before you go to a party': Analysis of a Vodka Cruiser advertising campaign. Drug
Alcohol Rev 2018;37:36-41].
PMID- 28401608
TI - Putting knowledge to work in clinical practice: Understanding experiences of
preceptorship as outcomes of interconnected domains of learning.
AB - AIMS AND OBJECTIVES: To explore how preceptor support can assist newly qualified
nurses to put knowledge to work across interconnected forms of knowledge when
delegating to healthcare assistants. BACKGROUND: Current literature on
preceptorship in nursing has failed to explore how competence is underpinned by
knowledge frameworks in clinical practice. DESIGN: An ethnographic case study in
three hospital sites in England (2011-2014). METHODS: Data collection included
participant observation, interviews with 33 newly qualified nurses, 10 healthcare
assistants and 12 ward managers. Data were analysed using thematic analysis. A
tool to assist newly qualified nurses to delegate and supervise newly qualified
nurses during the preceptorship period was developed and piloted with thirteen
newly qualified nurses in the same sites. A process evaluation was undertaken.
FINDINGS: Focusing on a key task for newly qualified nurses, delegation to
healthcare assistants, we argue that preceptorship can support newly qualified
nurses as they put knowledge to work in the transition from qualifying student to
newly qualified nurses. In supportive ward cultures, limited access to formal
preceptorship can be bolstered by team support. newly qualified nurses in less
supportive ward cultures may have both a greater need for preceptorship and fewer
compensatory mechanisms available to them when formal preceptorship is not
available. We argue that organisational learning contexts and individual learning
styles (interconnected domains of learning) are key to understanding effective
preceptorship. CONCLUSIONS: We suggest that putting knowledge to work early in
their careers with preceptorship support may assist newly qualified nurses to
develop confidence and competence in delegation and supervision of healthcare
assistants. RELEVANCE TO CLINICAL PRACTICE: Our findings suggest that newly
qualified nurses need to be supported by effective preceptorship in their
learning as they transition from undergraduate to post graduate. Preceptorship
programmes at ward and organisational level need to recognise the intensity of
the learning required during this transition phase.
PMID- 28401609
TI - Platinum-Based Organometallic Folders for the Recognition of Electron-Deficient
Aromatic Substrates.
AB - A series of platinum complexes with cis-oriented polyaromatic N-heterocyclic
carbene ligands were prepared and characterized. The relative disposition of the
polyaromatic ligands about the metal cause these compounds to behave as
metallofolders, featuring a cavity defined by the void space between the
polyaromatic functionalities. The complexes were used as receptors of organic
molecules, whereby selective affinity was displayed for electron-deficient
aromatic substrates, such as 1,2,4,5-tetracyanobenzene (TCNB), 2,4,7-trinitro-9
fluorenone (TNFLU), and 1,4,5,8-naphtalenetetracarboxylic dianhydride (NTCDA).
The binding affinities of two of the metallofolders with these substrates were
determined by means of 1 H NMR titrations. Electrospray mass spectrometry (ESI
MS) was also used to assess the affinities. The molecular structure of one of the
platinum folders was determined in the presence of TCNB, showing the clear
interaction between this guest molecule and the folder formed by the two mutually
cis-oriented polyaromatic ligands. This work demonstrates how the presence of the
mutually cis-oriented polyaromatic ligands may be a very useful tool for the
preparation of metal-based receptors.
PMID- 28401610
TI - The potential for mycobiont sharing between shrubs and seedlings to facilitate
tree establishment after wildfire at Alaska arctic treeline.
AB - Root-associated fungi, particularly ectomycorrhizal fungi (EMF), are critical
symbionts of all boreal tree species. Although climatically driven increases in
wildfire frequency and extent have been hypothesized to increase vegetation
transitions from tundra to boreal forest, fire reduces mycorrhizal inoculum.
Therefore, changes in mycobiont inoculum may potentially limit tree-seedling
establishment beyond current treeline. We investigated whether ectomycorrhizal
shrubs that resprout after fire support similar fungal taxa to those that
associate with tree seedlings that establish naturally after fire. We then
assessed whether mycobiont identity correlates with the biomass or nutrient
status of these tree seedlings. The majority of fungal taxa observed on shrub and
seedling root systems were EMF, with some dark septate endophytes and ericoid
mycorrhizal taxa. Seedlings and adjacent shrubs associated with similar arrays of
fungal taxa, and there were strong correlations between the structure of seedling
and shrub fungal communities. These results show that resprouting postfire shrubs
support fungal taxa compatible with tree seedlings that establish after wildfire.
Shrub taxon, distance to the nearest shrub and fire severity influenced the
similarity between seedling and shrub fungal communities. Fungal composition was
correlated with both foliar C:N ratio and seedling biomass and was one of the
strongest explanatory variables predicting seedling biomass. While correlative,
these results suggest that mycobionts are important to nutrient acquisition and
biomass accrual of naturally establishing tree seedlings at treeline and that
mycobiont taxa shared by resprouting postfire vegetation may be a significant
source of inoculum for tree-seedling establishment beyond current treeline.
PMID- 28401611
TI - Pegylated bovine carboxyhaemoglobin utilisation in a thrombotic thrombocytopenic
purpura patient.
AB - OBJECTIVE: To determine if pegylated bovine carboxyhaemoglobin can be utilised in
a thrombotic thrombocytopenic purpura (TTP) patient. BACKGROUND: TTP is a
condition characterized by thrombotic microangiopathy and has a high mortality
rate when left untreated. Therapeutic plasma exchange is well established as the
most effective and evidence-based treatment of TTP. METHODS: The ability to
administer plasma exchange therapy is limited in Jehovah's Witnesses who decline
blood products due to religious beliefs. Pegylated bovine carboxyhaemoglobin is a
novel oxygen transfer agent in development for the management of complications of
ischaemia due to acute anaemia. RESULTS: Treatment was well tolerated, with grade
1 paresthesia of the right face and arm 1 h after the first infusion of
Sanguinate, which spontaneously resolved and did not recur, and grade 1 cardiac
troponin elevation after receiving the medication (with peak at 0.079 ng mL-1 ),
but further workup with electrocardiogram and echocardiogram was unremarkable. By
discharge on day 19, the patient's haemoglobin increased to 8.8 g dL-1 and
platelet count to 221 000. CONCLUSIONS: We report the first case of TTP in a
Jehovah's Witness that was successfully managed with the use of pegylated bovine
carboxyhaemoglobin as an adjunct medication.
PMID- 28401612
TI - Codiversification of gastrointestinal microbiota and phylogeny in passerines is
not explained by ecological divergence.
AB - Vertebrate gut microbiota (GM) is comprised of a taxonomically diverse consortium
of symbiotic and commensal microorganisms that have a pronounced effect on host
physiology, immune system function and health status. Despite much research on
interactions between hosts and their GM, the factors affecting inter- and
intraspecific GM variation in wild populations are still poorly known. We
analysed data on faecal microbiota composition in 51 passerine species (319
individuals) using Illumina MiSeq sequencing of bacterial 16S rRNA (V3-V4
variable region). Despite pronounced interindividual variation, GM composition
exhibited significant differences at the interspecific level, accounting for
approximately 20%-30% of total GM variation. We also observed a significant
correlation between GM composition divergence and host's phylogenetic divergence,
with strength of correlation higher than that of GM vs. ecological or life
history traits and geographic variation. The effect of host's phylogeny on GM
composition was significant, even after statistical control for these confounding
factors. Hence, our data do not support codiversification of GM and passerine
phylogeny solely as a by-product of their ecological divergence. Furthermore, our
findings do not support that GM vs. host's phylogeny codiversification is driven
primarily through trans-generational GM transfer as the GM vs. phylogeny
correlation does not increase with higher sequence similarity used when
delimiting operational taxonomic units. Instead, we hypothesize that the GM vs.
phylogeny correlation may arise as a consequence of interspecific divergence of
genes that directly or indirectly modulate composition of GM.
PMID- 28401613
TI - Implementing augmentative and alternative communication in critical care
settings: Perspectives of healthcare professionals.
AB - AIMS AND OBJECTIVES: To describe the perspectives of healthcare professionals
caring for intubated patients on implementing augmentative and alternative
communication (AAC) in critical care settings. BACKGROUND: Patients in critical
care settings subjected to endotracheal intubation suffer from a temporary
functional speech disorder and can also experience anxiety, stress and delirium,
leading to longer and more complicated hospitalisation and rehabilitation. Little
is known about the use of AAC in critical care settings. METHOD: The design was
informed by interpretive descriptive methodology along with the theoretical
framework symbolic interactionism, which guided the study of healthcare
professionals (n = 48) in five different intensive care units. Data were
generated through participant observations and 10 focus group interviews.
RESULTS: The findings represent an understanding of the healthcare professionals'
perspectives on implementing AAC in critical care settings and revealed three
themes. Caring Ontology was the foundation of the healthcare professionals'
profession. Cultural Belief represented the actual premise in the interactions
during the healthcare professionals' work, saving lives in a biomedical setting
whilst appearing competent and efficient, leading to Triggered Conduct and giving
low priority to psychosocial issues like communication. CONCLUSION: Lack of the
ability to communicate puts patients at greater risk of receiving poorer
treatment, which supports the pressuring need to implement and use AAC in
critical care. It is documented that culture in biomedical paradigms can have
consequences that are the opposite of the staffs' ideals. The findings may guide
staff in implementing AAC strategies in their communication with patients and at
the same time preserve their caring ontology and professional pride. RELEVANCE TO
CLINICAL PRACTICE: Improving communication strategies may improve patient safety
and make a difference in patient outcomes. Increased knowledge of and familiarity
with AAC strategies may provide healthcare professionals with an enhanced feeling
of competence.
PMID- 28401614
TI - Suppression of interictal spikes during phasic rapid eye movement sleep: a
quantitative stereo-electroencephalography study.
AB - Tonic and phasic rapid eye movement (REM) sleep seem to represent two different
brain states exerting different effects on epileptic activity. In particular,
interictal spikes are suppressed strongly during phasic REM sleep. The reason for
this effect is not understood completely. A different level of synchronization in
phasic and tonic REM sleep has been postulated, yet never measured directly. Here
we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and
tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five
with type II focal cortical dysplasia and four with hippocampal sclerosis.
Moreover, we applied different quantitative measures to evaluate the level of
synchronization at the local and global scale during phasic and tonic REM sleep.
We found a lower spike rate in phasic REM sleep, both within and outside the
seizure onset zone. This effect seems to be independent from the
histopathological substrate and from the brain region, where epileptic activity
is produced (temporal versus extra-temporal). A higher level of synchronization
was observed during tonic REM sleep both on a large (global) and small (local)
spatial scale. Phasic REM sleep appears to be an interesting model for
understanding the mechanisms of suppression of epileptic activity.
PMID- 28401615
TI - Development, validation and testing of a nursing home to emergency room transfer
checklist.
AB - AIMS AND OBJECTIVES: To develop and test the feasibility of an instrument to
support patients' nursing home to emergency room transfer. BACKGROUND: Transfers
from a nursing home care facility to an acute care facility such as a hospital
emergency room are common. However, the prevalence of an information gap for
transferring residents' health data to acute care facility is high. An evidence
based transfer instrument, which could fill this gap, is lacking. DESIGN:
Development of a nursing home to emergency room transfer checklist, validation of
items using the Delphi method and testing the feasibility and benefits of using
the nursing home to emergency room transfer checklist. METHODS: Items were
developed based on qualitative data from previous research. Delphi validation,
retrospective chart review (baseline data) and a 6-month prospective study design
were applied to test the feasibility of using the checklist. Variables for
testing the feasibility of the checklist included residents' 30-day readmission
rate and length of hospital stay. RESULTS: Development of the nursing home to
emergency room transfer checklist resulted in four main parts: (i) demographic
data of the nursing home resident; (ii) critical data for nursing home to
emergency room transfer; (iii) contact information and (iv) critical data for
emergency room to nursing home transfer. Two rounds of Delphi validation resulted
in a mean score (standard deviation) ranging from 4.39 (1.13)-4.98 (.15). Time
required to complete the checklist was 3-5 min. Use of the nursing home to
emergency room transfer checklist resulted in a 30-day readmission rate of 13.4%,
which was lower than the baseline rate of 15.9%. CONCLUSIONS: The nursing home to
emergency room transfer checklist was developed for transferring nursing home
residents to an emergency room. The instrument was found to be an effective tool
for this process. RELEVANCE TO CLINICAL PRACTICE: Use of the nursing home to
emergency room transfer checklist for nursing home transfers could fill the
information gap that exists when transferring older adults between facilities
such as nursing homes and hospitals.
PMID- 28401616
TI - Searching for Staircases: Strengthening the Connections Between the Emergency
Department and the Intensive Care Unit.
PMID- 28401617
TI - The effectiveness of crisis resource management and team debriefing in
resuscitation education of nursing students: A randomised controlled trial.
AB - AIMS AND OBJECTIVES: The aim of this study was to investigate (i) whether
integrating a course on crisis resource management principles and team
debriefings in simulation training, increases self-efficacy, team efficacy and
technical skills of nursing students in resuscitation settings and (ii) which
phases contribute the most to these outcomes. BACKGROUND: Crisis resource
management principles have been introduced in health care to optimise teamwork.
Simulation training offers patient safe training opportunities. There is evidence
that simulation training increases self-efficacy and team efficacy but the
contribution of the different phases like crisis resource management principles,
simulation training and debriefing on self-efficacy, team efficacy and technical
skills is not clear. DESIGN: Randomised controlled trial in a convenience sample
(n = 116) in Belgium. Data were collected between February 2015-April 2015.
METHODS: Participants in the intervention group (n = 60) completed a course on
crisis resource management principles, followed by a simulation training session,
a team debriefing and a second simulation training session. Participants in the
control group (n = 56) only completed two simulation training sessions. The
outcomes self-efficacy, team efficacy and technical skills were assessed after
each simulation training. An ancillary analysis of the learning effect was
conducted. RESULTS: The intervention group increased on self-efficacy (2.13%, p =
.02) and team efficacy (9.92%, p < .001); the control group only increased
significantly on team efficacy (4.5%, p = .001). The intervention group scored
significantly higher on team efficacy (8.49%, p < .001) compared to the control
group. CONCLUSION: Combining crisis resource management principles and team
debriefings in simulation training increases self-efficacy and team efficacy. The
debriefing phase contributes the most to these effects. RELEVANCE TO CLINICAL
PRACTICE: By partnering with healthcare settings, it becomes possible to offer
interdisciplinary simulation training that can increase patient safety.
PMID- 28401618
TI - Tailoring mineralocorticoid receptor antagonist therapy in heart failure
patients: are we moving towards a personalized approach?
AB - The aim of personalized medicine is to offer a tailored approach to each patient
in order to provide the most effective therapy, while reducing risks and side
effects. The use of mineralocorticoid receptor antagonists (MRAs) has
demonstrated major benefits in heart failure with reduced ejection fraction
(HFrEF), results with challenging inconsistencies in heart failure with preserved
ejection fraction (HFpEF), and 'neutral' preliminary results in acute heart
failure. Data derived from landmark trials are generally applied in a 'one size
fits all' manner and the development and implementation of more personalized MRA
management would offer the potential to improve outcomes and reduce side effects.
However, the personalization of pharmacotherapy regimens remains poorly defined
in the cardiovascular field (in light of current knowledge) and until further
trials targeting specific subpopulations have been conducted, MRAs should be
provided to the great majority of HFrEF patients in the absence of
contraindication. Spironolactone should be considered for symptomatic HFpEF
patients with elevated natriuretic peptides. In the near future, trials should
target HFrEF patients using exclusion criteria sourced from landmark trials (e.g.
severe renal impairment), select more homogeneous HFpEF populations (e.g. with
elevated BNP and structural abnormalities on echocardiography), and determine
which patients are likely to benefit from MRAs (e.g. according to prespecified
biomarkers).
PMID- 28401619
TI - Non-compliance to infectious disease deferral criteria among Hong Kong's blood
donors.
AB - BACKGROUND AND OBJECTIVES: Donor screening alone cannot eliminate the risk of
transfusion-transmitted HIV infection. Donor deferral according to established
criteria is a supplemental strategy, which has focused largely on men who have
sex with men (MSM). A study was conducted to determine the compliance of non-MSM
donors with such criteria and examine its implications on blood safety. MATERIALS
AND METHODS: Chinese donors who have just donated blood at blood donor centres in
Hong Kong were recruited. Based on the contents of the routinely administered
predonation Health Screening Questionnaires, participants were requested to
complete a survey to assess their practice of deferrable risk behaviours and
lifestyle encounters, using tablet computers. RESULTS: Over an 8-week period in
mid-2016, 1614 donors (male-to-female ratio 1.23) had enrolled in the survey,
accounting for 40% of donors giving blood on the survey days. The proportion of
respondents who gave blood despite having deferrable HIV risk was 5%: MSM 1.2%
(of the male donors); non-MSM risk behaviours 2.6%; risky lifestyle encounters
2.1%. If inconsistent declaration and suspected risk behaviours were included,
the total non-compliance rate became 10.8%. Male donors had a higher prevalence
of deferrable behavioural risk, even after excluding MSM. Unawareness and non
acceptability were main reasons for non-compliance. CONCLUSION: The non
compliance rate of donors to deferral was high, although the ultimate infection
risk might be small in the presence of universal screening. Simplification of
questionnaires, focus on time-limited deferral and a reduction of deferral items
may improve the deferral mechanism without compromising blood safety.
PMID- 28401620
TI - ATP4A autoimmunity in pediatric patients with type 1 diabetes and its
relationship to blood count, iron metabolism, and vitamin B12.
AB - OBJECTIVE: We aimed to assess the prevalence of autoantibodies against the 4A
subunit of the gastric proton pump (ATP4A) in pediatric type 1 diabetes (T1D)
patients and explore the relationship between ATP4A positivity and blood cell
count, iron turnover, and vitamin B12 concentration. SUBJECTS: The study included
94 (59% female) T1D children (aged 12.5 +/- 4.1 years, T1D duration 4.2 +/- 3.6
years, HbA1c 7.3 +/- 1.5% (57 +/- 12.6 mmol/mol) with no other autoimmune
diseases. METHODS: ATP4A antibodies were measured in T1D patients using a
radioimmunoprecipitation assay. Blood cell count, iron concentration, total iron
binding capacity, ferritin, transferrin, hepcidin, and vitamin B12 concentration
were measured in all the study participants. RESULTS: A total of 16 (17%)
children were ATP4A positive. Serum concentrations of ferritin were significantly
lower in ATP4A positive than in antibody negative subjects (P = .034). Overall
the levels of ATP4A antibodies (ATP4A Index) correlated positively with the age
at T1D diagnosis (r = 0.228, P = .026) and negatively with ferritin levels (r =
0.215, P = .037). In ATP4A positive patients, the ATP4A Index correlated
positively with age at diagnosis (r = 0.544, P = .032) and negatively with
vitamin B12 levels (r = -0.685, P = .004). CONCLUSIONS: ATP4A antibodies were
present in a significant proportion of children with T1D. Higher ATP4A levels in
T1D children are associated with lower, yet still fitting within the normal
range, levels of vitamin B12, and ferritin. Routine screening of T1D children for
gastric autoimmunity (ATP4A) should be considered with follow-up of those
positive for vitamin B12 and iron deficiency.
PMID- 28401621
TI - Mouse models of severe asthma: Understanding the mechanisms of steroid
resistance, tissue remodelling and disease exacerbation.
AB - Severe asthma has significant disease burden and results in high healthcare
costs. While existing therapies are effective for the majority of asthma
patients, treatments for individuals with severe asthma are often ineffective.
Mouse models are useful to identify mechanisms underlying disease pathogenesis
and for the preclinical assessment of new therapies. In fact, existing mouse
models have contributed significantly to our understanding of
allergic/eosinophilic phenotypes of asthma and facilitated the development of
novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are
effective in relevant subsets of severe asthma patients. Unfortunately, non
allergic/non-eosinophilic asthma, steroid resistance and disease exacerbation
remain areas of unmet clinical need. No mouse model encompasses all features of
severe asthma. However, mouse models can provide insight into pathogenic pathways
that are relevant to severe asthma. In this review, as examples, we highlight
models relevant to understanding steroid resistance, chronic tissue remodelling
and disease exacerbation. Although these models highlight the complexity of the
immune pathways that may underlie severe asthma, they also provide insight into
new potential therapeutic approaches.
PMID- 28401622
TI - PREDICTing Mortality in the Emergency Department: External Validation and
Derivation of a Clinical Prediction Tool.
AB - BACKGROUND: The Choosing Wisely campaign has called for better engagement of
palliative and hospice care services for patients in the emergency department
(ED). PREDICT is a clinical prediction tool that was derived in an Australian ED
cohort. It assesses a patient's risk of mortality at 1 year to select those who
would benefit from advanced care planning. Such goals-of-care discussion can
improve patients' ability to communicate what they want out of their healthcare
and, in cases of end of life, potentially reduce the number of futile
interventions. Using a cutoff of 13 points, PREDICT had a reported 95.3%
specificity and 53.9% sensitivity for 1-year mortality. We externally validated
PREDICT and derived a simpler modified PREDICT tool to systematically identify
high-risk patients eligible for goals-of-care discussions and palliative care
consultation in the ED. METHODS: This was an observational cohort study of a
random sample of 927 patients aged 55+ seen in the ED in 2014. We identified
advance healthcare directives (AHDs) on file. We summarized diagnostic accuracy
of the clinical tool to predict 1-year mortality using sensitivity, specificity,
and area under the curve (AUC). We refined PREDICT using multivariable modeling.
We followed reporting guidelines including STrengthening the Reporting of
OBservational studies in Epidemiology (STROBE) for cohort studies and Standards
for Reporting of Diagnostic Accuracy (STARD). RESULTS: A total of 927 patients
were included: 55.0% were male, 63 (7.0%) were nursing home residents, 389
(42.0%) patients had an AHD in their medical record at the time of ED visit, and
245 (26.4%) were deceased at 1 year. Of the 780 patients with PREDICT scores <
13, a total of 164 (21.0%; 95% confidence interval [CI] = 18.3-24.1) were
deceased at 1 year, and of the 147 patients with PREDICT scores >= 13, a total of
81 (55.1%; 95% CI = 46.7-63.2) were deceased at 1 year. The AUC of the PREDICT
score was 0.717 (95% CI = 0.680-0.754), sensitivity was 33.1% (95% CI = 27.3
39.4), and specificity was 90.3% (95% CI = 87.8-92.4) to predict 1-year
mortality. The modified PREDICT tool resulted in an AUC of 0.709 (95% CI = 0.671
0.747). We decided to select this model as the preferred model, as the variable
of intensive care unit (ICU) admission with multiorgan failure can be difficult
to assess in the ED and may delay advanced care planning. Reweighting the score
did not improve fit or the AUC, so points assigned to each variable were not
adjusted. CONCLUSION: PREDICT is an easy tool to administer to be able to
identify patients who are at high risk of 1-year mortality and who could benefit
from AHDs, goals-of-care discussion, and when appropriate in the context of an
end-of-life setting, palliative medicine consultation. External validation of
PREDICT was successful in our population. We simplified PREDICT and derived a new
tool, the modified PREDICT minus ICU tool, without significantly altering the
sensitivity, specificity, and AUC for death at 1 year. The next steps include
external validation of the newly derived rule and prospective implementation.
PMID- 28401623
TI - The ignored roles of microRNAs in alopecia areata.
PMID- 28401624
TI - Unexpected population response to increasing temperature in the context of a
strong species interaction.
AB - Climate change is driving large changes in the spatial and temporal distributions
of species, with significant consequences for individual populations. Community-
and ecosystem-level implications of altered species distributions may be complex
and challenging to anticipate due to the cascading effects of disrupted
interactions among species, which may exhibit threshold responses to extreme
climatic events. Toxic, bloom-forming cyanobacteria like Microcystis are expected
to increase worldwide with climate change, due in part to their high temperature
optima for growth. In addition, invasive zebra mussels (Dreissena polymorpha)
have caused an increase in Microcystis aeruginosa, a species typically associated
with eutrophication, in low-nutrient lakes. We conducted a 13-yr study of a M.
aeruginosa population in a low-nutrient lake invaded by zebra mussels. In 10 of
the 13 years, there was a significant positive relationship between M. aeruginosa
biomass and accumulated degree days, which are projected to increase with climate
change. In contrast, Microcystis biomass was up to an order of magnitude lower
than predicted by the above relationship during the other three years, including
the warmest in the data set, following repeated heat-induced mass mortality of D.
polymorpha. Thus, the positive relationship between Microcystis biomass and
temperature was negated when its facilitating species was suppressed during a
series of exceptionally warm summers. Predicting the net response of a species to
climate change may therefore require, at minimum, quantification of responses of
both the focal species and species that strongly interact with it over
sufficiently long time periods to encompass the full range of climatic
variability. Our results could not have been predicted from existing data on the
short-term responses of these two interacting species to increased temperature.
PMID- 28401625
TI - Fatal case of cutaneous-sparing orolaryngeal zoster in a renal transplant
recipient.
AB - Herpesvirus infections in solid organ transplant (SOT) recipients are a
significant cause of morbidity and mortality. We report a case of herpes zoster
(HZ) in a kidney transplant recipient while receiving belatacept, a CTLA-4
inhibitor that prevents acute rejection. The patient presented with
oropharyngolaryngeal mucosal lesions that subsequently disseminated resulting in
pneumonitis and meningo-encephalitis. Very late-onset HZ can occur and can
present atypically in SOT recipients. Delayed recognition and treatment may
result in poor outcomes, as illustrated by this case.
PMID- 28401626
TI - A theory-informed qualitative exploration of social and environmental
determinants of physical activity and dietary choices in adolescents with
intellectual disabilities in their final year of school.
AB - BACKGROUND: The prevalence of obesity is higher in those with intellectual
disabilities than the general population. The aim of the study was to understand
the determinants of physical activity and dietary patterns in this population
during their final year of school. METHOD: Qualitative data were generated from
10 interviews with adolescents with mild-moderate intellectual disabilities. Data
were analysed using deductive thematic analysis, employing Self-Determination
Theory as a theoretical framework. RESULTS: Adolescents' environment and social
interactions play a pivotal role in influencing physical activity and dietary
patterns. Three themes emerged from the analysis: situatedness, motivation and
wider environmental influences. CONCLUSIONS: School structure, high self-efficacy
and social connectedness facilitate increased physical activity and healthier
diet in adolescents with intellectual disabilities. Home life, low self-efficacy
and a lack of social connectedness can serve as a barrier to PA and a healthy
diet.
PMID- 28401627
TI - Development of Semiconducting Polymer Nanoparticles for Photoacoustic Imaging.
AB - Semiconducting polymer nanoparticles (SPNs) have evolved into a new class of
photonic materials with great potential for biomedical applications. Depending on
the polymer structures, SPNs can be developed into optical agents for
fluorescence and chemiluminescence imaging, photosensitizers for photodynamic
therapy, and heat converters for photothermal therapy. In this feature article,
recent work is summarized on the development of SPNs for in vivo photoacoustic
(PA) imaging, a state-of-the-art imaging modality that converts light energy into
mechanical acoustic waves to provide deep tissue penetration. The structure
property relationship and doping approaches are discussed to reveal the
importance of promoting nonradiative decay in amplifying the PA brightness of
SPNs. Moreover, their imaging applications, including lymph node mapping, tumor
imaging, and monitoring of pathological indexes, are highlighted. These studies
demonstrate that SPNs can serve as versatile PA agents for advanced molecular
imaging applications.
PMID- 28401628
TI - Metabolomics reveals new metabolic perturbations in children with type 1
diabetes.
AB - OBJECTIVE: Using an untargeted metabolomics approach we investigated the
metabolome of children with type 1 diabetes (T1D) in comparison with healthy
peers and explored the contribution of HbA1c and clinical features to the
observed difference. RESEARCH DESIGN AND METHODS: We enrolled children with T1D
aged 6-15 years, attending the pediatric diabetes clinic of University of Padova
(Italy). Healthy controls were enrolled on voluntary basis and matched for age,
sex, pubertal status, body mass index (BMI). We performed a liquid chromatography
and mass spectrometry analysis (LC-MS) on fasting urinary samples of the 2
groups. RESULTS: A total of 56 patients with T1D aged (11.4 +/- 2.2) years, and
30 healthy controls (10.7 +/- 2.8) years were enrolled. We identified 59 urinary
metabolites having a higher level in children with T1D, mainly represented by
gluco- and mineralcorticoids, phenylalanine and tryptophan catabolites
(kynurenine), small peptides, glycerophospholipids, fatty acids, and gut
bacterial products. We did not find any association between HbA1c, pubertal
status, disease duration, and metabolome profile within the case group.
CONCLUSIONS: T1D profoundly disrupts the metabolome of pediatric patients. The
excess of cortisol and aldosterone may contribute to the development of
macrovascular complications in adulthood, while the increase of tryptophan
derivates may have a role in neuronal damage associated to hyperglycemia.
Determinants of such findings, other than HbA1c, should be explored.
PMID- 28401629
TI - A 1,470 nm diode laser in stapedotomy: Mechanical, thermal, and acoustic effects.
AB - BACKGROUND AND OBJECTIVES: Multiple laser systems have been investigated for
their use in stapes surgery in patients with otosclerosis. The diode 1,470 nm
laser used in this study is an attractive laser system because it is easily
transported and relatively inexpensive in use. This wavelength has relative high
absorption in water. This study aimed to investigate the mechanical, thermal, and
acoustic effects of the diode 1,470 nm laser on a stapes in an inner ear model.
MATERIALS AND METHODS: Experiments were performed in an inner ear model including
fresh frozen human stapes. High-speed imaging with frame rates up to 2,000 frames
per second (f/s) was used to visualize the effects in the vestibule during
fenestration of the footplate. A special high-speed color Schlieren technique was
used to study thermal effects. The sound produced by perforation was recorded by
a hydrophone. Single pulse settings of the diode 1,470 nm laser were 100 ms, 3 W.
RESULTS: Diode 1,470 nm laser fenestration showed mechanical effects with small
vapor bubbles and pressure waves pushed into the vestibule. Thermal imaging
visualized an increase temperature underneath the stapes footplate. Acoustic
effects were limited, but larger sounds levels were reached when vaporization
bubbles arise and explode in the vestibule. CONCLUSION: The diode 1,470 nm laser
highly absorbs in perilymph and is capable of forming a clear fenestration in the
stapes. An overlapping laser pulse will increase the risk of vapor bubbles,
pressure waves, and heating the vestibule. As long as we do not know the possible
damage of these effects to the inner ear function, it seems advisable to use the
laser with less potential harm. Lasers Surg. Med. 49:619-624, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28401630
TI - Causation or selection - examining the relation between education and
overweight/obesity in prospective observational studies: a meta-analysis.
AB - Numerous studies have investigated the association between education and
overweight/obesity. Yet less is known about the relative importance of causation
(i.e. the influence of education on risks of overweight/obesity) and selection
(i.e. the influence of overweight/obesity on the likelihood to attain education)
hypotheses. A systematic review was performed to assess the linkage between
education and overweight/obesity in prospective studies in general populations.
Studies were searched within five databases, and study quality was appraised with
the Newcastle-Ottawa scale. In total, 31 studies were considered for meta
analysis. Regarding causation (24 studies), the lower educated had a higher
likelihood (odds ratio: 1.33, 1.21-1.47) and greater risk (risk ratio: 1.34, 1.08
1.66) for overweight/obesity, when compared with the higher educated. However,
these associations were no longer statistically significant when accounting for
publication bias. Concerning selection (seven studies), overweight/obese
individuals had a greater likelihood of lower education (odds ratio: 1.57, 1.10
2.25), when contrasted with the non-overweight or non-obese. Subgroup analyses
were performed by stratifying meta-analyses upon different factors. Relationships
between education and overweight/obesity were affected by study region, age
groups, gender and observation period. In conclusion, it is necessary to consider
both causation and selection processes in order to tackle educational
inequalities in obesity appropriately.
PMID- 28401631
TI - Disease burden, comorbidity and geriatric syndromes in the Australian aged care
population.
AB - OBJECTIVE: To describe the burden of disease in the Australian residential aged
care population. METHODS: Cross-sectional analysis of Aged Care Funding
Instrument data. RESULTS: Dementia (48%), depression (22.5%) and arthritis
(14.2%) were the most prevalent chronic diseases in this population. Unclassified
conditions such as falls, pain and urinary incontinence were also significant
burdens in this population (17.1%). Circulatory, musculoskeletal and unclassified
conditions were the most prevalent comorbidities across all common medical
groups. Dementia and depression were the most common comorbid mental health
conditions across all medical groups. CONCLUSION: The challenges for evaluating
clinical care in Australian residential aged care are many. Delivering good
clinical care should be a priority for aged care providers given the high burden
of chronic disease and comorbidity. An informative starting point could be to
target management of the most prevalent and burdensome conditions and
comorbidities.
PMID- 28401632
TI - Role of four-dimensional echocardiography with high-definition flow imaging and
spatiotemporal image correlation in detecting fetal pulmonary veins.
AB - BACKGROUND: Prenatal diagnosis of fetal total anomalous pulmonary vein connection
(TAPVC) remains challenging for most screening sonographers. The purpose of this
study was to evaluate the use of four-dimensional echocardiography with high
definition flow imaging and spatiotemporal image correlation (4D-HDFI) in
identifying pulmonary veins in normal and TAPVC fetuses. MATERIAL & METHODS: We
retrospectively reviewed and performed 4D-HDFI in 204 normal and 12 fetuses with
confirmed diagnosis of TAPVC. Cardiac volumes were available for postanalysis to
obtain 4D-rendered images of the pulmonary veins. For the normal fetuses, two
other traditional modalities including color Doppler and HDFI were used to detect
the number of pulmonary veins and comparisons were made between each of these
traditional methods and 4D-HDFI. RESULTS: For conventional echocardiography, HDFI
modality was superior to color Doppler in detecting more pulmonary veins in
normal fetuses throughout the gestational period. 4D-HDFI was the best method
during the second trimester of pregnancy in identifying normal fetal pulmonary
veins. 4D-HDFI images vividly depicted the figure, course, and drainage of
pulmonary veins in both normal and TAPVC fetuses. CONCLUSION: HDFI and the
advanced 4D-HDFI technique could facilitate identification of the anatomical
features of pulmonary veins in both normal and TAPVC fetuses; 4D-HDFI therefore
provides additional and more precise information than conventional
echocardiography techniques.
PMID- 28401633
TI - Functional soil metagenomics: elucidation of polycyclic aromatic hydrocarbon
degradation potential following 12 years of in situ bioremediation.
AB - A culture-independent function-based screening approach was used to assess the
microbial aerobic catabolome for polycyclic aromatic hydrocarbons degradation of
a soil subjected to 12 years of in situ bioremediation. A total of 422 750 fosmid
clones were screened for key aromatic ring-cleavage activities using 2,3
dihydroxybiphenyl as substrate. Most of the genes encoding ring-cleavage enzymes
on the 768 retrieved positive fosmids could not be identified using primer-based
approaches and, thus, 205 fosmid inserts were sequenced. Nearly two hundred
extradiol dioxygenase encoding genes of three different superfamilies could be
identified. Additional key genes of aromatic metabolic pathways were identified,
including a high abundance of Rieske non-heme iron oxygenases that provided
detailed information on enzymes activating aromatic compounds and enzymes
involved in activation of the side chain of methylsubstituted aromatics. The
gained insights indicated a complex microbial network acting at the site under
study, which comprises organisms similar to recently identified Immundisolibacter
cernigliae TR3.2 and Rugosibacter aromaticivorans Ca6 and underlined the great
potential of an approach that combines an activity-screening, a cost-effective
high-throughput sequencing of fosmid clones and a phylogenomic-routed and
manually curated database to carefully identify key proteins dedicated to aerobic
degradation of aromatic compounds.
PMID- 28401634
TI - Moving Between Dialogic Reflexive Processes In Systemic Family Therapy Training:
An Interpretative Phenomenological Study of Trainees' Experience.
AB - In this article, we present a qualitative research study concerning the ways that
systemic family therapy trainees experience reflexivity while in training. There
is inadequate theorizing and limited research concerning reflexivity in family
therapy, particularly from trainees' perspective. In our study, we used
Interpretative Phenomenological Analysis to analyse transcripts of semistructured
interviews with 10 systemic family therapy trainees. Here, we present one of the
four superordinate analytic themes, entitled "Moving between reflexive
processes". Our analysis suggests that trainees seem to experience reflexivity as
a multifaceted, dialogic process, which occurs both at an inner and at an outer
space and both synchronically but also subsequently to the therapeutic/training
process. We conclude by raising implications for family therapy training. Video
abstract accessible by clicking here.
PMID- 28401635
TI - Electrokinetic device design and constraints for use in high conductance
solutions.
AB - The quest for new cell-free DNA and exosome biomarker-based molecular diagnostics
require fast and efficient sample preparation techniques. Conventional methods
for isolating these biomarkers from blood are both time-consuming and laborious.
New electrokinetic microarray devices using dielectrophoresis (DEP) to isolate
cell-free DNA and exosome biomarkers have now greatly improved the sample
preparation process. Nevertheless, these devices still have some limitations when
used with high conductance biological fluids, e.g. blood, plasma, and serum. This
study demonstrates that electrochemical damage may occur on the platinum
electrodes of DEP microarray devices. It further examines two model device
designs that include a parallel wire arrangement and a planar array. Effective
isolation of fluorescent beads with parallel wires is shown under low-conductance
conditions (10-4 S/m), but electrothermal flow overcomes DEP forces under high
conductance conditions (>0.1 S/m). Planar devices are shown to be effective under
high conductance conditions (~1 S/m) without the deleterious effects of
electrothermal flow. This study provides new insights into design compromises and
limitations for producing future electrokinetic devices for better performance
with high conductance solutions.
PMID- 28401636
TI - Contribution of different bacterial dispersal sources to lakes: Population and
community effects in different seasons.
AB - The diversity and composition of lake bacterial communities are driven by the
interplay between local contemporary environmental conditions and dispersal of
cells from the surroundings, i.e. the metacommunity. Still, a conceptual
understanding of the relative importance of the two types of factors is lacking.
For instance, it is unknown which sources of dispersal are most important and
under which circumstances. Here, we investigated the seasonal variation in the
importance of dispersal from different sources (mixing, precipitation, surface
runoff and sediment resuspension) for lake bacterioplankton community and
population dynamics. For that purpose, two small forest lakes and their dispersal
sources were sampled over a period of 10 months. The influence of dispersal on
communities and populations was determined by 454 sequencing of the 16S rRNA gene
and SourceTracker analysis. On the community level direct effects of dispersal
were questionable from all sources. Instead we found that the community of the
preceding sampling occasion, representing growth of resident bacteria, was of
great importance. On the population level, however, dispersal of individual taxa
from the inlet could be occasionally important even under low water flow. The
effect of sediment resuspension and precipitation appeared small.
PMID- 28401637
TI - Alcohol-tolerant mutants of cyanobacterium Synechococcus elongatus PCC 7942
obtained by single-cell mutant screening system.
AB - Enhancement of alcohol tolerance in microorganisms is an important strategy for
improving bioalcohol productivity. Although cyanobacteria can be used as a
promising biocatalyst to produce various alcohols directly from CO2 , low
productivity, and low tolerance against alcohols are the main issues to be
resolved. Nevertheless, to date, a mutant with increasing alcohol tolerance has
rarely been reported. In this study, we attempted to select isopropanol (IPA)
tolerant mutants of Synechococcus elongatus PCC 7942 using UV-C-induced random
mutagenesis, followed by enrichment of the tolerant candidates in medium
containing 10 g/L IPA and screening of the cells with a high growth rate in the
single cell culture system in liquid medium containing 10 g/L IPA. We
successfully acquired the most tolerant strain, SY1043, which maintains the
ability to grow in medium containing 30 g/L IPA. The photosynthetic oxygen
evolving activities of SY1043 were almost same in cells after 72 h incubation
under light with or without 10 g/L IPA, while the activity of the wild-type was
remarkably decreased after the incubation with IPA. SY1043 also showed higher
tolerance to ethanol, 1-butanol, isobutanol, and 1-pentanol than the wild type.
These results suggest that SY1043 would be a promising candidate to improve
alcohol production using cyanobacteria. Biotechnol. Bioeng. 2017;114: 1771-1778.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28401638
TI - The effects of high-intensity interval training vs. moderate-intensity continuous
training on body composition in overweight and obese adults: a systematic review
and meta-analysis.
AB - OBJECTIVE: The objective of this study is to compare the effects of high
intensity interval training (HIIT) and moderate-intensity continuous training
(MICT) for improvements in body composition in overweight and obese adults.
METHODS: Trials comparing HIIT and MICT in overweight or obese participants aged
18-45 years were included. Direct measures (e.g. whole-body fat mass) and
indirect measures (e.g. waist circumference) were examined. RESULTS: From 1,334
articles initially screened, 13 were included. Studies averaged 10 weeks * 3
sessions per week training. Both HIIT and MICT elicited significant (p < 0.05)
reductions in whole-body fat mass and waist circumference. There were no
significant differences between HIIT and MICT for any body composition measure,
but HIIT required ~40% less training time commitment. Running training displayed
large effects on whole-body fat mass for both HIIT and MICT (standardized mean
difference -0.82 and -0.85, respectively), but cycling training did not induce
fat loss. CONCLUSIONS: Short-term moderate-intensity to high-intensity exercise
training can induce modest body composition improvements in overweight and obese
individuals without accompanying body-weight changes. HIIT and MICT show similar
effectiveness across all body composition measures suggesting that HIIT may be a
time-efficient component of weight management programs.
PMID- 28401639
TI - Targeting low-density lipoprotein cholesterol with PCSK9 inhibitors.
AB - Over the past quarter century, clinical trials have consistently demonstrated
that lowering levels of low-density lipoprotein cholesterol (LDL-C) with statins
reduces the rate of major adverse cardiovascular events. However, the findings
that many patients continue to experience events or harbour inappropriately high
LDL-C levels despite intensive statin therapy and the clinical reality of statin
intolerance suggests that additional therapeutic strategies are required in order
to achieve more effective reductions in cardiovascular risk. The emergence of
inhibitory monoclonal antibodies targeted against proprotein convertase
subtilisin kexin type 9 (PCSK9) provides a novel approach to reducing LDL-C
levels. The current experience of PCSK9 inhibitors and implications for clinical
use and cost effectiveness will be reviewed.
PMID- 28401640
TI - Bacterial and plant natriuretic peptides improve plant defence responses against
pathogens.
AB - Plant natriuretic peptides (PNPs) have been implicated in the regulation of ions
and water homeostasis, and their participation in the plant immune response has
also been proposed. Xanthomonas citri ssp. citri contains a gene encoding a PNP
like protein (XacPNP) which has no homologues in other bacteria. XacPNP mimics
its Arabidopsis thaliana homologue AtPNP-A by modifying host responses to create
favourable conditions for pathogen survival. However, the ability of XacPNP to
induce plant defence responses has not been investigated. In order to study
further the role of XacPNP in vivo, A. thaliana lines over-expressing XacPNP,
lines over-expressing AtPNP-A and AtPNP-A-deficient plants were generated. Plants
over-expressing XacPNP or AtPNP-A showed larger stomatal aperture and were more
resistant to saline or oxidative stress than were PNP-deficient lines. In order
to study further the role of PNP in biotic stress responses, A. thaliana leaves
were infiltrated with pure recombinant XacPNP, and showed enhanced expression of
genes related to the defence response and a higher resistance to pathogen
infections. Moreover, AtPNP-A expression increased in A. thaliana on Pseudomonas
syringae pv. tomato (Pst) infection. This evidence led us to analyse the
responses of the transgenic plants to pathogens. Plants over-expressing XacPNP or
AtPNP-A were more resistant to Pst infection than control plants, whereas PNP
deficient plants were more susceptible and showed a stronger hypersensitive
response when challenged with non-host bacteria. Therefore, XacPNP, acquired by
horizontal gene transfer, is able to mimic PNP functions, even with an increase
in plant defence responses.
PMID- 28401641
TI - A conserved alpha-proteobacterial small RNA contributes to osmoadaptation and
symbiotic efficiency of rhizobia on legume roots.
AB - Small non-coding RNAs (sRNAs) are expected to have pivotal roles in the adaptive
responses underlying symbiosis of nitrogen-fixing rhizobia with legumes. Here, we
provide primary insights into the function and activity mechanism of the
Sinorhizobium meliloti trans-sRNA NfeR1 (Nodule Formation Efficiency RNA).
Northern blot probing and transcription tracking with fluorescent promoter
reporter fusions unveiled high nfeR1 expression in response to salt stress and
throughout the symbiotic interaction. The strength and differential regulation of
nfeR1 transcription are conferred by a motif, which is conserved in nfeR1
promoter regions in alpha-proteobacteria. NfeR1 loss-of-function compromised
osmoadaptation of free-living bacteria, whilst causing misregulation of salt
responsive genes related to stress adaptation, osmolytes catabolism and membrane
trafficking. Nodulation tests revealed that lack of NfeR1 affected
competitiveness, infectivity, nodule development and symbiotic efficiency of S.
meliloti on alfalfa roots. Comparative computer predictions and a genetic
reporter assay evidenced a redundant role of three identical NfeR1 unpaired anti
Shine-Dalgarno motifs for targeting and downregulation of translation of multiple
mRNAs from transporter genes. Our data provide genetic evidence of the
hyperosmotic conditions of the endosymbiotic compartments. NfeR1-mediated gene
regulation in response to this cue could contribute to coordinate nutrient uptake
with the metabolic reprogramming concomitant to symbiotic transitions.
PMID- 28401642
TI - Misfit of organizational and personal work standards and its longitudinal effect
on physicians' depressiveness.
AB - The misfit of organizational and personal work standards and its relationship to
health is an issue that has rarely been investigated in hospital physicians. In
particular, compensatory factors for the negative effects of a misfit of
organizational and personal work standards remain unknown. Our longitudinal study
investigated whether autonomous experiences at work and during leisure time
compensate for the effects of a misfit of organizational and personal work
standards on depressive complaints. Data were collected through surveys of German
hospital physicians. Two surveys were conducted with a time lag of 12 months. One
hundred sixty-one physicians participated in both surveys. To test our
hypothesis, we used path analysis and controlled for autoregressive effects. The
results confirmed that a misfit of organizational and personal work standards
affects depressive complaints over a 12-month period. Additionally, leisure
autonomy compensates for the negative effects of misfit. Contrary to that, high
levels of job autonomy were found to intensify the effects of a misfit of
organizational and personal work standards. Our findings support previous
research assumptions that job autonomy has the potential to add to stress.
Hospitals must ensure that physicians can adequately use their job autonomy.
PMID- 28401644
TI - Comprehensive Dissection of Transcriptome Data and Regulatory Factors in
Pancreatic Cancer Cells.
AB - Features of pancreatic cancers include high mortality rates caused by rapid tumor
progression and a lack of effective therapy. Underpinning the molecular
mechanisms involved in the alteration of the gene expression program in the
pancreatic cancer remains to be understood. In the current study, we performed a
comprehensive analysis using 282 pancreatic tumor and normal samples from seven
independent expression data sets to provide a better view on the interactions
between different transcription factors (TFs) and the most affected biological
pathways in pancreatic cancer. We highlighted common differentially expressed
genes (DEGs) and common affected processes within pancreatic cancer samples. We
revealed 16 main DE-TFs that regulated gene expression alterations as well as the
most significant processes in pancreatic cancer compared to normal cells. For
example, we found the upregulated FOXM1 to be a top regulator of pancreatic
cellular transformation based on results from different analyses, including from
its regulation of gene regulatory networks, its presence in protein complex, its
significant regulation of genes related to cancer pathways, and its regulation of
most of the identified DE-TFs. Furthermore, we provided a model and assessed the
role of different DE-TFs in the regulation of the most affected pancreatic- and
cancer-specific processes. In conclusion, our bioinformatics meta-analysis of
high throughput expression data sets, besides clarifying common affected genes
and pathways, also showed the mechanisms involved in regulating these common
profiles. Our results, especially for DE-TFs, could potentially be useful for
screening for pancreatic cancer, and for confirming or determining novel
pharmacological targets. J. Cell. Biochem. 118: 3976-3985, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28401645
TI - Body composition and micronutrient deficiencies in patients with an acute
exacerbation of chronic obstructive pulmonary disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multisystem
disorder. Abnormal body composition (BC) and micronutrient deficiencies (MD)
contribute significantly to morbidity associated with acute exacerbations of COPD
(AECOPD). COPD is a major health problem in Western Sydney. AIMS: To study the
pattern of BC and MD in patients admitted with an AECOPD to Western Sydney.
METHODS: The BC and serum levels of selected micronutrients were recorded in
prospective, consecutive patients admitted to hospital with AECOPD in Western
Sydney. RESULTS: A total of 94 patients was enrolled, 43% female, and the average
age was 69.8 +/- 8.2 years (SD). Admission spirometry revealed a mean spirometric
ratio of 0.42 +/- 0.14 (SD) and a severely reduced mean percentage FEV1 of
predicted at 29.1% +/- 11.6 (SD). A total of 51% of the population was overweight
or obese, with an average body mass index of 25.9 +/- 7.7 kg/m2 (SD). When fat
free mass (FFM) was also considered 23% were cachectic, 9% had muscle atrophy and
6% were semi-starved. Vitamin D deficiency (<50 nmol/L) was present in 53% and
vitamin B12 deficiency (<222 pmol/L) was present in 31%. Anaemia was present in
30%, with 38% of these being iron deficient. Living status (alone or with family)
was not associated with BC or micronutrient deficiencies (MD). Patients with >=2
hospital admissions for AECOPD had a significantly lower mean B12 level (280.5 +/
143.0 pmol/L (SD) vs 360.5 +/- 198.1 pmol/L (SD) P = 0.042). The malnutrition
screening tool, a questionnaire-based assessment of malnutrition used by the
local health area did not accurately predict patients with abnormal BC or those
with >2 MD. CONCLUSIONS: In patients admitted with AECOPD, the majority of
subjects were overweight or obese, with a low FFM. MD, in particular B12 and
vitamin D, were common. Interventional studies addressing BC and MD are required
to assess potential improvements in AECOPD-related morbidity and mortality.
PMID- 28401646
TI - Exploring the association between childhood and adolescent obesity and
depression: a meta-analysis.
AB - This meta-analysis aimed to evaluate the association between childhood and
adolescent obesity and depression. We systematically searched PubMed, PsycInfo,
EMBASE and Science Direct for studies that compared prevalence of depression and
depressive symptoms in normal weight and obese children and adolescents.
Observational studies were included if they reported body mass index and assessed
depression by validated instruments or diagnostic interviews. Quality assessment
was performed using the Newcastle-Ottawa scale. We used the random-effect model
to calculate the pooled odds ratios, standard mean differences (SMDs) and
subgroup analysis. Findings for a total of 51,272 participants were pooled across
18 studies and examined. Our analyses demonstrated a positive association between
childhood and adolescent obesity and depression (pooled odds ratio = 1.34, 95%
confidence interval [CI]: 1.1-1.64, p = 0.005) and more severe depressive
symptoms (SMD = 0.23, 95% CI: 0.025-0.44, p = 0.028) in the obese groups.
Overweight subjects were not more likely to have either depression (pooled odds
ratio = 1.16, 95% CI: 0.93-1.44, p = 0.19) or depressive symptoms (SMD = 0, 95%
CI: -0.101 to 0.102, p = 0.997). Non-Western and female obese subjects were
significantly more likely to have depression and severe depressive symptoms (p <
0.05). In conclusion, obese children and adolescents are more likely to suffer
from depression and depressive symptoms, with women and non-Western people at
higher risk.
PMID- 28401643
TI - Ultrafast compartmentalized relaxation time mapping with linear algebraic
modeling.
AB - PURPOSE: To dramatically accelerate compartmental-average longitudinal (T1 ) and
transverse (T2 ) relaxation measurements using the minimal-acquisition linear
algebraic modeling (SLAM) method, and to validate it in phantoms and humans.
METHODS: Relaxation times were imaged at 3 Tesla in phantoms, in the abdomens of
six volunteers, and in six brain tumor patients using standard inversion recovery
and multi-spin-echo sequences. k-space was fully sampled to provide reference T1
and T2 measurements, and SLAM was performed using a limited set of phase encodes
from central k-space. Anatomical compartments were segmented on scout images post
acquisition, and SLAM reconstruction was implemented using two algorithms.
Compartment-average T1 and T2 measurements were determined retroactively from
fully sampled data sets, and proactively from SLAM data sets at acceleration
factors of up to 16. Values were compared with reference measurements. The
compartment's localization properties were analyzed using the discrete spatial
response function. RESULTS: At 16-fold acceleration, compartment-average SLAM T1
measurements agreed with the full k-space compartment-average results to within
0.0% +/- 0.7%, 1.4% +/- 3.4%, and 0.5% +/- 2.9% for phantom, abdominal, and brain
T1 measurements, respectively. The corresponding T2 measurements agreed within
0.2% +/- 1.9%, 0.9% +/- 7.9%, and 0.4% +/- 5.8%, respectively. CONCLUSION: SLAM
can dramatically accelerate relaxation time measurements when compartmental or
lesion-average values can suffice, or when standard relaxometry is precluded by
scan-time limitations. Magn Reson Med 79:286-297, 2018. (c) 2017 International
Society for Magnetic Resonance in Medicine.
PMID- 28401647
TI - MG53 anchored by dysferlin to cell membrane reduces hepatocyte apoptosis which
induced by ischaemia/reperfusion injury in vivo and in vitro.
AB - Hepatic ischaemia/reperfusion (HIR) induces severe damage on hepatocyte cell
membrane, which leads to hepatocyte death and the subsequent HIR injury. In this
study, we investigated the role and the mechanism of mitsugumin-53 (MG53), a
novel cell membrane repair protein, in protecting the liver against HIR injury.
Rats were subjected to sham operation or 70% warm HIR with or without recombined
MG53 (rhMG53), caudal vein-injected 2 hrs before inducing HIR. In vitro, cultured
hepatocyte AML12 cells were subjected to hypoxia/reoxygenation (H/R) in the
presence of rhMG53 and/or dysferlin gene shRNAs or adenovirus transfection. HIR
resulted in severe liver injury manifested as severe liver histological changes
and increased AST and ALT release. Post-ischaemic hepatic oxidative stress was
significantly enhanced demonstrated by elevated dihydroethidium level, increased
4-hydroxynonenal, enhanced 15-F2t-isoprostane and decreased SOD activity. rhMG53
administration attenuated post-HIR liver injury, decreased liver oxidative stress
and further enhanced dysferlin protein expression and its colocalization with
MG53. Similarly, H/R induced AML12 cell injury and oxidative stress, which were
abolished by either rhMG53 or dysferlin overexpression but were exacerbated by
dysferlin gene knockdown. Dysferlin overexpression further increased H/R-induced
increased colocalization of MG53 and dysferlin. In conclusion, MG53 was anchored
by dysferlin to reduce oxidative stress and cell death and attenuate HIR injury.
PMID- 28401648
TI - Current Status and Perspectives Regarding LNA-Anti-miR Oligonucleotides and
microRNA miR-21 Inhibitors as a Potential Therapeutic Option in Treatment of
Colorectal Cancer.
AB - Colorectal cancer (CRC) is among the leading causes of cancer-related death,
principally due to its metastatic spread and multifactorial chemoresistance. The
therapeutic failure can also be explained by inter- or intra-tumor genetic
heterogeneity and tumor stromal content. Thus, the identification of novel
prognostic biomarkers and therapeutic options are warranted in the management of
CRC patients. There are data showing that microRNA-21 is elevated in different
types of cancer, particularly colon adenocarcinoma and that this is association
with a poor prognosis. This suggests that microRNA-21 may be of value as a
potential therapeutic target. Furthermore, locked nucleic acid (LNA)-modified
oligonucleotides have recently emerged as a therapeutic option for targeting
dysregulated miRNAs in cancer therapy, through antisense-based gene silencing.
Further work is required to identify innovative anticancer drugs that improve the
current therapy either through novel combinatorial approaches or with better
efficacy than conventional drugs. We aimed to provide an overview of the
preclinical and clinical studies targeting key dysregulated signaling pathways in
CRC as well as the therapeutic application of LNA-modified oligonucleotides, and
miR inhibitors in the treatment of CRC patients. J. Cell. Biochem. 118: 4129
4140, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401649
TI - Papular acantholytic dyskeratosis of vulva in setting of Hailey-Hailey.
PMID- 28401651
TI - Trap-State Suppression and Improved Charge Transport in PbS Quantum Dot Solar
Cells with Synergistic Mixed-Ligand Treatments.
AB - The power conversion efficiency of colloidal PbS-quantum-dot (QD)-based solar
cells is significantly hampered by lower-than-expected open circuit voltage (VOC
). The VOC deficit is considerably higher in QD-based solar cells compared to
other types of existing solar cells due to in-gap trap-induced bulk recombination
of photogenerated carriers. Here, this study reports a ligand exchange procedure
based on a mixture of zinc iodide and 3-mercaptopropyonic acid to reduce the VOC
deficit without compromising the high current density. This layer-by-layer solid
state ligand exchange treatment enhances the photovoltaic performance from 6.62
to 9.92% with a significant improvement in VOC from 0.58 to 0.66 V. This study
further employs optoelectronic characterization, X-ray photoelectron
spectroscopy, and photoluminescence spectroscopy to understand the origin of VOC
improvement. The mixed-ligand treatment reduces the sub-bandgap traps and
significantly reduces bulk recombination in the devices.
PMID- 28401650
TI - Caenorhabditis elegans orthologs of human genes differentially expressed with age
are enriched for determinants of longevity.
AB - We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes
selected based on orthology to human genes differentially expressed with age. We
find substantial enrichment in genes for which knockdown increased lifespan. This
enrichment is markedly higher than published genomewide longevity screens in C.
elegans and similar to screens that preselected candidates based on longevity
correlated metrics (e.g., stress resistance). Of the 50 genes that affected
lifespan, 46 were previously unreported. The five genes with the greatest impact
on lifespan (>20% extension) encode the enzyme kynureninase (kynu-1), a neuronal
leucine-rich repeat protein (iglr-1), a tetraspanin (tsp-3), a regulator of
calcineurin (rcan-1), and a voltage-gated calcium channel subunit (unc-36).
Knockdown of each gene extended healthspan without impairing reproduction. kynu
1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and
Huntington's disease. Each gene displayed a distinct pattern of interaction with
known aging pathways. In the context of published work, kynu-1, tsp-3, and rcan-1
are of particular interest for immediate follow-up. kynu-1 is an understudied
member of the kynurenine metabolic pathway with a mechanistically distinct impact
on lifespan. Our data suggest that tsp-3 is a novel modulator of hypoxic
signaling and rcan-1 is a context-specific calcineurin regulator. Our results
validate C. elegans as a comparative tool for prioritizing human candidate aging
genes, confirm age-associated gene expression data as valuable source of novel
longevity determinants, and prioritize select genes for mechanistic follow-up.
PMID- 28401652
TI - The role of dehydroepiandrosterone on functional innate immune responses to acute
stress.
AB - The androgen dehydroepiandrosterone (DHEA) responds to stress activation,
exhibits anti-glucocorticoid properties, and modulates immunity in diverse ways,
yet little is known of its role in acute stress responses. In this study, the
effects of DHEA and its sulfate ester DHEA-S on human male immune function during
exposure to an acute stressor is explored. Variation in DHEA, DHEA-S,
testosterone, and cortisol, along with bacterial killing assays, was measured in
response to a modified Trier Social Stress test in 27 young adult males. Cortisol
was positively related to salivary innate immunity but only for participants who
also exhibited high DHEA responses. Additionally, DHEA positively and DHEA-S
negatively predicted salivary immunity, but the opposite was observed for serum
based innate immunity. The DHEA response to acute stress appears to be an
important factor in stress-mediated immunological responses, with differential
effects on immunity dependent upon the presence of other hormones, primarily
cortisol and DHEA-S. These results suggest that DHEA plays an important role,
alongside other hormones, in modulating immunological shifts during acute stress.
PMID- 28401655
TI - Modern Aspects of the Smiles Rearrangement.
AB - The Smiles rearrangement is an intramolecular SN Ar reaction, breaking a C-X
single bond and forming a new C-X or C-C bond though ipso substitution. Its vast
scope, in terms of nucleophile, leaving group, and ring-size of the transition
state, make it a powerful tool for arene functionalization, as it can be employed
strategically to switch easily-forged bonds with more difficult connections that
would be challenging to realize in the intermolecular mode. The reaction has
received significantly renewed attention in recent years, as advances in areas
such as arene C-X bond formation and radical generation have been harnessed for
new arene syntheses through Smiles chemistry. In addition, new reaction modes
have been discovered, such as the Clayden rearrangement of lithiated ureas,
creating innovative applications for Smiles rearrangements in asymmetric
arylation. This Minireview will discuss advances in these areas in the recent
literature, covering both two-electron, polar Smiles rearrangements along with
single-electron radical transformations.
PMID- 28401653
TI - Selective blockade of B7-H3 enhances antitumour immune activity by reducing
immature myeloid cells in head and neck squamous cell carcinoma.
AB - Immature myeloid cells including myeloid-derived suppressor cells (MDSCs) and
tumour-associated macrophages (TAMs) promote tumour growth and metastasis by
facilitating tumour transformation and angiogenesis, as well as by suppressing
antitumour effector immune responses. Therefore, strategies designed to reduce
MDSCs and TAMs accumulation and their activities are potentially valuable
therapeutic goals. In this study, we show that negative immune checkpoint
molecule B7-H3 is significantly overexpressed in human head and neck squamous
cell carcinoma (HNSCC) specimen as compared with normal oral mucosa. Using
immunocompetent transgenic HNSCC models, we observed that targeting inhibition of
B7-H3 reduced tumour size. Flow cytometry analysis revealed that targeting
inhibition of B7-H3 increases antitumour immune response by decreasing
immunosuppressive cells and promoting cytotoxic T cell activation in both tumour
microenvironment and macroenvironment. Our study provides direct in vivo evidence
for a rationale for B7-H3 blockade as a future therapeutic strategy to treat
patients with HNSCC.
PMID- 28401654
TI - Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder?
AB - Approximately 30% of individuals with autism spectrum disorder (ASD) have
elevated whole blood serotonin (5-HT) levels. Genetic linkage and association
studies of ASD and of whole blood 5-HT levels as a quantitative trait have
revealed sexual dimorphism. Few studies have examined the presence of a sex
difference on hyperserotonemia within ASD. To assess whether the rate of
hyperserotonemia is different in males than in females with ASD, we measured
whole blood 5-HT levels in 292 children and adolescents with ASD, the largest
sample in which this biomarker has been assessed. Based upon previous work
suggesting that hyperserotonemia is more common prior to puberty, we focused our
analysis on the 182 pre-pubertal children with ASD. 42% of pre-pubertal
participants were within the hyperserotonemia range. In this population, we found
that males were significantly more likely to manifest hyperserotonemia than
females (P = 0.03). As expected, no significant difference was found in the post
pubertal population. Additional work will be needed to replicate this intriguing
finding and to understand whether it could potentially explain differences in
patterns of ASD risk between males and females. Autism Res 2017, 10: 1417-1423.
(c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28401656
TI - Improving access to better care for people with knee and/or hip pain: service
evaluation of allied health professional-led primary care.
AB - INTRODUCTION: Chronic knee and hip pain is prevalent, impairing mobility,
function and quality of life. Allied health professions (AHPs) are better trained
and have more time than general practitioners in primary care to advise and
support people to adopt healthier lifestyles (maintain healthy weight, increase
physical activity) that reduce joint pain. We evaluated whether AHP-led primary
care delivering person-centred, practical lifestyle coaching was a feasible,
effective way to manage chronic knee and/or hip pain. METHODS: At initial
assessment the 'Joint Pain Advisor' assessed pain, function, quality of life,
physical activity, waist circumference and body mass, taught simple self
management strategies and used behaviour change techniques (motivational
interviewing, goal setting, action/coping planning) to alter participants'
lifestyles. Participants were invited for 6-week and 6-month reviews, when the
Advisor reassessed clinical outcomes, fed back progress and reinforced health
messages. Feasibility and effectiveness of the service was evaluated using
quantitative and qualitative methods. RESULTS: Uptake of the service was good:
498 people used the service. Between initial assessment and reviews,
participants' pain, function, quality of life, weight, waist circumference and
physical activity improved (p < 0.005). Service user satisfaction was high; they
reported easier access to advice and support tailored to their needs that
translated into clinical benefits and a more efficient pathway reducing
unnecessary consultations and investigations. Relatively few people returned for
a 6-month review as they considered they had received sufficient advice.
CONCLUSIONS: AHP-led care is a popular, effective, efficient and sustainable way
to manage joint pain, without compromising safety or quality of care.
PMID- 28401657
TI - Validation of a modified early warning score-linked Situation-Background
Assessment-Recommendation communication tool: A mixed methods study.
AB - AIMS AND OBJECTIVES: To develop and validate a modified Situation-Background
Assessment-Recommendation communication tool incorporating components of the Cape
Town modified early warning score vital signs chart for reporting early signs of
clinical deterioration. BACKGROUND: Reporting early signs of physiological and
clinical deterioration could prevent "failure to rescue" or unexpected intensive
care admission, cardiac arrest or death. A structured communication tool
incorporating physiological and clinical parameters allows nurses to provide
pertinent information about a deteriorating patient in a logical order. DESIGN:
Mixed methods instrument development and validation. METHODS: We used a
sequential three-phase method: cognitive interviews, content validation and inter
rater reliability testing to validate a self-designed communication tool.
Participants were purposively selected expert nurses and doctors in government
sector hospitals in Cape Town. RESULTS: Cognitive interviews with five experts
prompted most changes to the communication tool: 15/42 (35.71%) items were
modified. Content validation of a revised tool was high by a predetermined >=70%
of 18 experts: 4/49 (8.2%) items were modified. Inter-rater reliability testing
by two nurses indicated substantial to full agreement (Cohen's kappa .61-1) on
37/45 (82%) items. The one item achieving slight agreement (Cohen's kappa .20)
indicated a difference in clinical judgement. The high overall percentage
agreement (82%) suggests that the modified items are sound. Overall, 45 items
remained on the validated tool. CONCLUSION: The first modified early warning
score-linked Situation-Background-Assessment-Recommendation communication tool
developed in South Africa was found to be valid and reliable in a local context.
RELEVANCE TO CLINICAL PRACTICE: Nurses in South Africa can use the validated tool
to provide doctors with pertinent information about a deteriorating patient in a
logical order to prevent a serious adverse event. Our findings provide a
reference for other African countries to develop and validate communication tools
for reporting early signs of clinical deterioration.
PMID- 28401658
TI - Kreuth IV: European consensus proposals for treatment of haemophilia with
coagulation factor concentrates.
AB - INTRODUCTION: This report summarizes recommendations relating to haemophilia
therapy arising from discussions among experts from 36 European countries during
the 'Kreuth IV' meeting in May 2016. AIM: The objective of the meeting was for
experts in the field of haemophilia from across Europe to draft resolutions
regarding current issues relating to the treatment of haemophilia. RESULTS:
Hospitals providing clinical care for people with haemophilia and related
disorders are strongly recommended to seek formal designation as either European
Haemophilia Treatment Centres (EHTC) or European Haemophilia Comprehensive Care
Centres (EHCCC). There should be agreed national protocols or guidelines on
management of the ageing patient with haemophilia. The minimum consumption of
factor VIII and IX concentrate in any country should be 4 IU and 0.5 IU per
capita of general population respectively. Treatment for hepatitis C with direct
acting antiviral agents should be provided to all people with haemophilia on a
priority basis. Genotype analysis should be offered to all patients with severe
haemophilia. Genetic counselling, when given, should encompass the recommendation
that genetic relatives of the affected person be advised to seek genetic
counselling. People with inhibitors should have access to bypassing agents,
immune tolerance and elective surgery. National or regional tenders for factor
concentrates are encouraged. Outcome data including health related quality of
life should be collected. Treatment with extended half-life factors should be
individualized and protection against bleeding should be improved by increasing
trough levels. Steps should be taken to understand and minimize the risk of
inhibitor development. CONCLUSION: It is hoped that these recommendations will
help to foster equity of haemophilia care throughout Europe.
PMID- 28401659
TI - Dynamic Orthogonal Switching of a Thermoresponsive Self-Organized Helical
Superstructure.
AB - Controllable manipulation of self-organized dynamic superstructures of functional
molecular materials by external stimuli is an enabling enterprise. Herein, we
have developed a thermally driven, self-organized helical superstructure, i.e.,
thermoresponsive cholesteric liquid crystal (CLC), by integrating a judiciously
chosen thermoresponsive chiral molecular switch into an achiral liquid
crystalline medium. The CLC in lying state, in both planar and twisted nematic
cells, exhibits reversible in-plane orthogonal switching of its helical axis in
response to the combined effect of temperature and electric field. Consequently,
the direction of the cholesteric grating has been observed to undergo 90 degrees
switching in a single cell, enabling non-mechanical beam steering along two
orthogonal directions. The ability to reversibly switch the cholesteric gartings
along perpendicular directions by appropriately adjusting temperature and
electric field strength could facilitate their applications in 2D beam steering,
spectrum scanning, optoelectronics and beyond.
PMID- 28401660
TI - Depression, anxiety, and compulsive sexual behaviour among men in residential
treatment for substance use disorders: The role of experiential avoidance.
AB - : Nearly one-third of individuals in treatment for substance use disorders
endorse at-risk levels of compulsive sexual behaviours (CSBs). Untreated sexual
compulsivity may facilitate relapse for treatment-seeking men. Previous research
and theory suggest that CSBs are maintained by efforts to escape or alter
negative affect (e.g., depression and anxiety). However, this hypothesis has not
been examined within a sample of men in treatment for substance use disorders. In
an effort to better understand CSBs within a population of men with substance use
disorders, the present study is the first to examine experiential avoidance as
one potential mechanism underlying the relation between men's symptoms of
depression and anxiety and their use of CSBs. The present study reviewed medical
records of 150 men in residential treatment for substance use disorders.
Structural equation modelling was used to examine pathways from men's depression
and anxiety symptoms to CSBs directly and indirectly through experiential
avoidance while controlling for alcohol/drug problems and use. Results revealed
significant indirect effects of both depression and anxiety symptoms on CSB
through experiential avoidance. These results support and extend existing
research on CSB in a treatment population. Findings suggest that intervention
efforts for CSB may benefit by targeting men's avoidance of painful internal
events. KEY PRACTITIONER MESSAGE: Compulsive sexual behaviour is related to
symptoms of depression and anxiety amongst men in residential treatment for
substance use disorders. Experiential avoidance is positively related to
compulsive sexual behaviour amongst men with substance use disorders. For men in
treatment for substance use disorders, the relation between symptoms of
depression and anxiety and compulsive sexual behaviour is explained, in part, by
experiential avoidance. Helping men with substance use disorders develop more
adaptive methods of processing aversive experiences, as opposed to escaping them,
may reduce their use of compulsive sexual behaviours when faced with aversive
affect.
PMID- 28401661
TI - Chemical discrimination of lubricant marketing types using direct analysis in
real time time-of-flight mass spectrometry.
AB - RATIONALE: In comparison to other violent crimes, sexual assaults suffer from
very low prosecution and conviction rates especially in the absence of DNA
evidence. As a result, the forensic community needs to utilize other forms of
trace contact evidence, like lubricant evidence, in order to provide a link
between the victim and the assailant. METHODS: In this study, 90 personal bottled
and condom lubricants from the three main marketing types, silicone-based, water
based and condoms, were characterized by direct analysis in real time time of
flight mass spectrometry (DART-TOFMS). The instrumental data was analyzed by
multivariate statistics including hierarchal cluster analysis, principal
component analysis, and linear discriminant analysis. RESULTS: By interpreting
the mass spectral data with multivariate statistics, 12 discrete groupings were
identified, indicating inherent chemical diversity not only between but within
the three main marketing groups. A number of unique chemical markers, both major
and minor, were identified, other than the three main chemical components (i.e.
PEG, PDMS and nonoxynol-9) currently used for lubricant classification. The data
was validated by a stratified 20% withheld cross-validation which demonstrated
that there was minimal overlap between the groupings. CONCLUSIONS: Based on the
groupings identified and unique features of each group, a highly discriminating
statistical model was then developed that aims to provide the foundation for the
development of a forensic lubricant database that may eventually be applied to
casework. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28401662
TI - Early life programming of attention capacity in adolescents: The HELENA study.
AB - The study aims to examine the individual and combined association of early life
factors (birth weight, birth length, and any and exclusive breastfeeding) with
attention capacity in adolescents. The study included 421 European adolescents
(243 girls), aged 12.5-17.5 years, who participated in the Healthy Lifestyle in
Europe by Nutrition in Adolescence Study. Body weight and length at birth of
adolescents were collected from parental records. The duration of any and
exclusive breastfeeding were self-reported. The d2 Test of Attention was
administered to assess attention capacity. The main results showed that birth
weight, birth length, breastfeeding, and exclusive breastfeeding were related to
attention capacity in boys (beta ranging from 0.144 to 0.196; all p < .05) after
adjustment for age, centre, gestational age, maternal education, family affluence
scale, and body mass index. Among boys, differences in attention capacity were
found according to tertiles of birth weight and birth length (p < .05), as well
as borderline significant differences across groups of any and exclusive
breastfeeding (p = 0.055 and p = 0.108, respectively) after adjusting for
potential confounders. In addition, boys with 3 early life risk factors (low
birth weight, low birth length, and <3 months of breastfeeding) had significantly
lower scores in attention capacity compared with boys with 0 risk factors
(percentile score - 15.88; p = 0.009). In conclusion, early life factors, both
separately and combined, may influence attention capacity in male European
adolescents. Importantly, the combination of the 3 early life risk factors, low
birth weight, low birth length, and <3 months of breastfeeding, even in normal
ranges, may provide the highest reduction in attention capacity.
PMID- 28401664
TI - Rapid determination of oligomeric hindered amine light stabilizers in polymeric
materials.
AB - Hindered amine light stabilizers are essential for the stabilization of synthetic
polymers, particularly for materials used for outdoor applications. Although up
to now a considerable number of studies dealing with the analytics of this class
of stabilizers had been published, especially the determination of oligomeric
hindered amine light stabilizers is still an analytical challenge. In the current
work, a fast and simple liquid chromatographic method for the quantitative
determination of oligomeric hindered amine light stabilizers is presented. A key
aspect of this method is their completely different retention behavior depending
on the pH, enabling a single peak elution approach by a pH gradient run. This
allows a quantitation with simple UV detection independent of the actual
oligomeric composition. Calibration curves within the concentration range
relevant for the analysis of real polymer samples (LOQ = 70 mg/L) were
constructed with R2 values above 0.99. Spiked extracts from polyolefin samples
showed recovery rates between 97.3 and 102.9% for five different commercial
hindered amine light stabilizers. Relative standard deviations were between 2.0
and 3.9%. Furthermore, it was demonstrated that the employed approach can be
easily adapted for mass spectrometry detection.
PMID- 28401663
TI - Does Personality Matter in Diabetes Adherence? Exploring the Pathways between
Neuroticism and Patient Adherence in Couples with Type 2 Diabetes.
AB - BACKGROUND: Personality has received some attention in the Type 2 diabetes
literature; however, research has not linked personality and diabetes adherence
behaviors (diet and exercise), identified pathways through which they are
associated, nor taken into consideration important contextual factors that
influence behavior (the patient's partner). METHODS: Dyadic data from 117
married, heterosexual couples in which one member is diagnosed with Type 2
diabetes was used to explore associations between each partner's neuroticism and
patient dietary and exercise adherence through the pathways of negative affect,
depression symptoms, and couple-level diabetes efficacy (both patient and spouse
report of confidence in the patient's ability to adhere to diabetes management
regimens). RESULTS: Results revealed that higher levels of neuroticism were
associated with lower patient dietary and exercise adherence through (1) higher
levels of depression symptoms (for patients' neuroticism) and negative affect
(for spouses' neuroticism), and (2) lower levels of couple-level diabetes
efficacy. CONCLUSIONS: The results from this study provide evidence that both
patient and spouse personality traits are associated with patient dietary and
exercise adherence through increased emotional distress-albeit different
emotional pathways for patients and spouses-and lower couple confidence in the
patients' ability to manage their diabetes.
PMID- 28401665
TI - Conducting Molecular Nanomagnet of DyIII with Partially Charged TCNQ Radicals.
AB - Bifunctional electrically conducting single-molecule magnets are highly promising
platforms for non-volatile memory devices and quantum computing applications. The
development of these molecular materials, however, has largely been hindered by
the lack of straightforward synthetic methods. Herein a facile and modular
approach is demonstrated for the realization of bifunctional materials that does
not require electrochemical or chemical oxidation to obtain partially charged
organic radicals. Magnetic and electrical conductivity studies reveal that the
DyIII compound exhibits slow relaxation of the magnetization between 5.0-8.0 K
and semiconducting behavior over the range 180-350 K. DC magnetic fields have
been found to suppress the quantum tunneling of the magnetization and affect the
spin-canted antiferromagnetic interactions.
PMID- 28401666
TI - A model to increase rehabilitation adherence to home exercise programmes in
patients with varying levels of self-efficacy.
AB - Patient adherence to rehabilitation programmes is frequently low - particularly
adherence to home exercise programmes. Home exercise programmes have been
identified as complementary to clinic-based physical therapy in an orthopaedic
setting. Barriers to patient adherence have previously been identified within the
literature. Low self-efficacy is a barrier to adherence that clinicians have the
ability to have an impact on and improve. The theory of self-efficacy is defined
as a person's confidence in their ability to perform a task. This theory examines
the ability of a person to change through exerting control over inner processes
of goal setting, self-monitoring, feedback, problem solving and self-evaluation.
If clinicians are able to identify patients with low self-efficacy prior to the
prescription of a home exercise programme, adjustments to individualized care can
be implemented. Individualized care based on improving self-efficacy for home
exercise programmes may improve patient adherence to these programmes. The
purpose of this article was to use the theory of self-efficacy to direct
clinicians in providing individualized programmes to patients with varying levels
of self-efficacy.
PMID- 28401667
TI - Increased energy intake following sleep restriction in men and women: A one-size
fits-all conclusion?
AB - OBJECTIVE: This study assessed the degree of interindividual responses in energy
intake (EI) to an imposed sleep restriction versus habitual sleep duration
protocol. It also investigated participant (age, sex, ethnicity, and BMI) and
study (study site and protocol order) characteristics as potential contributors
to the variance in EI responses to sleep restriction between individuals.
METHODS: Data from two randomized crossover trials were combined. All
participants (n = 43; age: 31 +/- 7 years, BMI: 23 +/- 2 kg/m2 ) were free of
medical/sleep conditions, were nonsmokers, reported not performing shift work,
and had an average sleep duration of 7 to 9 hours per night. Ad libitum, 24-hour
EI was objectively assessed following sleep restriction (3.5-4 hours in bed per
night) and habitual sleep (7-9 hours in bed per night) conditions. RESULTS: Large
interindividual variations in EI change (DeltaEI) between restricted and habitual
sleep conditions were noted (-813 to 1437 kcal/d). Only phase order was
associated with DeltaEI (beta = -568 kcal/d, 95% confidence interval for beta =
921 to -215 kcal/d; P = 0.002); participants randomized to the habitual sleep
condition first had greater increases in EI when sleep was restricted (P = 0.01).
CONCLUSIONS: Large interindividual variations in DeltaEI following sleep
restriction were noted, suggesting that not all participants were negatively
impacted by the effects of sleep restriction.
PMID- 28401668
TI - Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of
the Active Species?
AB - Diverse biological activities of vanadium(V) drugs mainly arise from their
abilities to inhibit phosphatase enzymes and to alter cell signaling. Initial
interest focused on anti-diabetic activities but has shifted to anti-cancer and
anti-parasitic drugs. V-based anti-diabetics are pro-drugs that release active
components (e.g., H2 VO4- ) in biological media. By contrast, V anti-cancer drugs
are generally assumed to enter cells intact; however, speciation studies indicate
that nearly all drugs are likely to react in cell culture media during in vitro
assays and the same would apply in vivo. The biological activities are due to VV
and/or VIV reaction products with cell culture media, or the release of ligands
(e.g., aromatic diimines, 8-hydroxyquinolines or thiosemicarbazones) that bind to
essential metal ions in the media. Careful consideration of the stability and
speciation of V complexes in cell culture media and in biological fluids is
essential to design targeted V-based anti-cancer therapies.
PMID- 28401669
TI - Implementation of teaching on LGBT health care.
AB - BACKGROUND: Lesbian, gay, bisexual and transgender (LGBT) patients represent an
important proportion of the population. Despite the health inequalities and
barriers to health care noted within this group, there is little evidence of LGBT
focused education within medicine, dentistry or nursing. We introduced and
evaluated the effect of a half-day teaching session focused on LGBT health care,
delivered to year-2 students. CONTEXT: Initial informal discussion with year-2
and year-3 students suggested that the awareness of health inequalities other
than sexual health was limited, and that students had little awareness of other
issues such as gender dysphoria and heterosexism. We therefore targeted these
areas when developing the material. There is little evidence of LGBT-focused
education within medicine, dentistry or nursing INNOVATION: The session was
divided into two sections: a lecture and a workshop. The lecture provided an
introduction to issues around legislation, transgender health and health
inequalities, whereas the workshops involved a role-play focused on gender
dysphoria, followed by small group discussions on topics such as heterosexism and
sexual identity. Volunteer peer facilitators, some of whom identified as LGBT,
undertook a 2-hour training session to ensure that they were comfortable with
both the material and the group facilitation. Students completed a short
questionnaire before and after the session. IMPLICATIONS: Feedback was gathered
from 350 students between 2012 and 2015. Sixty-nine per cent of students rated
their competency level higher after the workshop, suggesting that they felt
better prepared to consult with LGBT patients. Written comments suggested that
the sessions are useful for students in terms of improving awareness of health
inequalities and enabling consultation skills practice in an informal
environment.
PMID- 28401671
TI - A case of xanthoma disseminatum treated with imatinib mesylate.
PMID- 28401672
TI - Multi-decadal time series of remotely sensed vegetation improves prediction of
soil carbon in a subtropical grassland.
AB - Soil carbon sequestration in agroecosystems could play a key role in climate
change mitigation but will require accurate predictions of soil organic carbon
(SOC) stocks over spatial scales relevant to land management. Spatial variation
in underlying drivers of SOC, such as plant productivity and soil mineralogy,
complicates these predictions. Recent advances in the availability of remotely
sensed data make it practical to generate multidecadal time series of vegetation
indices with high spatial resolution and coverage. However, the utility of such
data largely is unknown, only having been tested with shorter (e.g., 1-2 yr) data
summaries. Across a 2,000 ha subtropical grassland, we found that a long time
series (28 yr) of a vegetation index (Enhanced Vegetation Index; EVI) derived
from the Landsat 5 satellite significantly enhanced prediction of spatially
varying SOC pools, while a short summary (2 yr) was an ineffective predictor. EVI
was the best predictor for surface SOC (0-5 cm depth) and total measured SOC
stocks (0-15 cm). The optimum models for SOC in the upper soil layer combined EVI
records with elevation and calcium concentration, while deeper SOC was more
strongly associated with calcium availability. We demonstrate how data from the
open access Landsat archive can predict SOC stocks, a key ecosystem metric, and
illustrate the rich variety of analytical approaches that can be applied to long
time series of remotely sensed greenness. Overall, our results showed that SOC
pools were closely coupled to EVI in this ecosystem, demonstrating that
maintenance of higher average green leaf area is correlated with higher SOC. The
strong associations of vegetation greenness and calcium concentration with SOC
suggest that the ability to sequester additional SOC likely will rely on
strategic management of pasture vegetation and soil fertility.
PMID- 28401670
TI - Adolescents' behavioral and neural responses to e-cigarette advertising.
AB - Although adolescents are a group heavily targeted by the e-cigarette industry,
research in cue-reactivity has not previously examined adolescents' behavioral
and neural responses to e-cigarette advertising. This study addressed this gap
through two experiments. In Experiment One, adult traditional cigarette smokers
(n = 41) and non-smokers (n = 41) answered questions about e-cigarette and
neutral advertising images. The 40 e-cigarette advertising images that most
increased desire to use the product were matched to 40 neutral advertising images
with similar content. In Experiment Two, the 80 advertising images selected in
Experiment One were presented to adolescents (n = 30) during an functional
magnetic resonance imaging brain scan. There was a range of traditional cigarette
smoking across the sample with some adolescents engaging in daily smoking and
others who had never smoked. Adolescents self-reported that viewing the e
cigarette advertising images increased their desire to smoke. Additionally, all
participants regardless of smoking statuses showed significantly greater brain
activation to e-cigarette advertisements in areas associated with cognitive
control (left middle frontal gyrus), reward (right medial frontal gyrus), visual
processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal
lobule, left posterior cingulate, left angular gyrus) and memory (right
parahippocampus, left insula). Further, an exploratory analysis showed that
compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7)
displayed significantly greater neural activation to e-cigarette advertising
images in the left inferior temporal gyrus/fusiform gyrus, compared with their
responses to neutral advertising images. Overall, participants' brain responses
to e-cigarette advertisements suggest a need to further investigate the long-run
impact of e-cigarette advertising on adolescents.
PMID- 28401673
TI - Morphology of Modern Arrowhead Tips on Human Skin Analog.
AB - Archery has experienced a recent resurgence in participation and has seen
increases in archery range attendance and in children and young adults seeking
archery lessons. Popular literature and movies prominently feature protagonists
well versed in this form of weaponry. Periodic homicide cases in the United
States involving bows are reported, and despite this and the current interest in
the field, there are no manuscripts published on a large series of arrow wounds.
This experiment utilizes a broad selection of modern arrowheads to create wounds
for comparison. While general appearances mimicked the arrowhead shape, details
such as the presence of abrasions were greatly influenced by the design of the
arrowhead tip. Additionally, in the absence of projectiles or available history,
arrowhead injuries can mimic other instruments causing penetrating wounds. A
published resource on arrowhead injuries would allow differentiation of causes of
injury by forensic scientists.
PMID- 28401674
TI - Placebo-like response in absence of treatment in children with Autism.
AB - Caregiver report is the most common measure of change in pediatric psychiatry.
Yet, placebo response rates pose significant challenges to reliably detect a
treatment response. The present study simulated an eight-week clinical trial
protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the
feasibility and validity of several outcome measures. Twenty caregivers answered
questions about their child's behavior on their smartphone each week and
completed a battery of paper questionnaires during weeks one and eight. No
treatment was administered. Caregivers reported a significant decrease in problem
behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD
behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also
a trend of behavior improvement from smartphone questions but no significant
changes in clinical ratings of core diagnostic features of ASD. Participation in
a comprehensive protocol in the absence of a particular treatment significantly
influenced how caregivers perceived the severity of their children's problem
behaviors. These placebo-like effects represent substantial challenges for
randomized controlled trials (RCTs) that use treatment as usual and have
implications for future behavioral and pharmacological treatment trial designs.
Autism Res 2017, 10: 1567-1572. (c) 2017 International Society for Autism
Research, Wiley Periodicals, Inc.
PMID- 28401675
TI - Advanced model-based control strategies for the intensification of upstream and
downstream processing in mAb production.
AB - Current industrial trends encourage the development of sustainable,
environmentally friendly processes with minimal energy and material consumption.
In particular, the increasing market demand in biopharmaceutical industry and the
tight regulations in product quality necessitate efficient operating procedures
that guarantee products of high purity. In this direction, process
intensification via continuous operation paves the way for the development of
novel, eco-friendly processes, characterized by higher productivity and lower
production costs. This work focuses on the development of advanced control
strategies for (i) a cell culture system in a bioreactor and (ii) a
semicontinuous purification process. More specifically, we consider a fed-batch
culture of GS-NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent
Gradient Purification (MCSGP) for the purification process. The controllers are
designed following the PAROC framework/software platform and their capabilities
are assessed in silico, against the process models. It is demonstrated that the
proposed controllers efficiently manage to increase the system productivity,
returning strategies that can lead to continuous, stable process operation. (c)
2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966-988,
2017.
PMID- 28401677
TI - Embracing the co-operative society to better understand assembly of the gut
microbiota.
PMID- 28401676
TI - Regulation of solvent tolerance in Pseudomonas putida S12 mediated by mobile
elements.
AB - Organic solvent-tolerant bacteria are outstanding and versatile hosts for the bio
based production of a broad range of generally toxic aromatic compounds. The
energetically costly solvent tolerance mechanisms are subject to multiple levels
of regulation, involving among other mobile genetic elements. The genome of the
solvent-tolerant Pseudomonas putida S12 contains many such mobile elements that
play a major role in the regulation and adaptation to various stress conditions,
including the regulation of expression of the solvent efflux pump SrpABC. We
recently sequenced the genome of P. putida S12. Detailed annotation identified a
threefold higher copy number of the mobile element ISS12 in contrast to earlier
observations. In this study, we describe the mobile genetic elements and
elaborate on the role of ISS12 in the establishment and maintenance of solvent
tolerance in P. putida. We identified three different variants of ISS12 of which
a single variant exhibits a high translocation rate. One copy of this variant
caused a loss of solvent tolerance in the sequenced strain by disruption of srpA.
Solvent tolerance could be restored by applying selective pressure, leading to a
clean excision of the mobile element.
PMID- 28401678
TI - A and B antigen levels acquired by group O donor-derived erythrocytes following
ABO-non-identical transfusion or minor ABO-incompatible haematopoietic stem cell
transplantation.
AB - BACKGROUND AND OBJECTIVES: ABO-incompatible haematopoietic stem cell
transplantation (HSCT) presents a challenge to blood component transfusion. The
aim of this study was to investigate the weak blood group A or B antigen
expression by donor-derived group O red blood cells (RBC) observed following
transfusion or minor ABO-incompatible HSCT. In addition, in vitro experiments
were performed to elucidate possible mechanisms underlying this phenomenon.
MATERIALS AND METHODS: A sensitive flow cytometry assay for the semi
quantification of RBC A/B antigen levels was used to assess patient samples and
evaluate in vitro experiments. RESULTS: Analysis of blood samples from patients,
originally typed as A, B and AB but recently transplanted or transfused with
cells from group O donors, revealed the A antigen expression on donor-derived
RBC, ranging from very low levels in non-secretor individuals to almost subgroup
Ax -like profiles in group A secretors. The B antigen expression was less readily
detectable. In vitro experiments, in which group O donor RBC were incubated with
(i) group A/B secretor/non-secretor donor plasma or (ii) group A/B donor RBC in
the absence of plasma, supported the proposed adsorption of A/B antigen-bearing
glycolipids from secretor plasma but also indicated a secretor-independent
mechanism for A/B antigen acquisition as well as direct cell-to-cell transfer of
ABO antigens. CONCLUSION: The in vivo conversion of donor-derived blood group O
RBC to ABO subgroup-like RBC after transfusion or minor ABO-incompatible HSCT
raises the question of appropriate component selection. Based on these data, AB
plasma should be transfused following ABO-incompatible HSCT.
PMID- 28401681
TI - Effect of dentin pretreatment with potassium oxalate: A 6-year follow-up.
AB - Oxalate-based products are effective against dentine sensitivity and have been
studied as an option to improve long-term adhesive bonding strength. Our aim was
to evaluate the effect of potassium oxalate on the microtensile bond strength
(uTBS) of the dentin/resin interface after 24 h, 1, and 6 years. Dentin on the
occlusal surface of 16 human premolars was exposed and etched with 35% phosphoric
acid. The teeth were divided into four groups. Two groups received 3%
monohydrated potassium oxalate and the following adhesive systems and composites:
Adper Scotchbond Multipurpose + FiltekZ350 (3M/ESPE) and Prime & Bond NT + Esthet
X (Dentsply). Two control groups did not receive potassium oxalate. Teeth were
cut into sticks and kept in distilled water at 37 degrees C for 24 h, 1, and 6
years. The sticks underwent uTBS testing after storage. ANOVA, Tukey's post hoc
test, and paired t test were used to compare storage times (alpha = 0.05). The
fracture mode of the specimens was classified under a stereomicroscope (40*).
Morphology of the hybrid layer and the fracture pattern were observed with
scanning electronic microscopy (SEM). Mean uTBS was high at 24 h and decreased
after 1 and 6 years. After 6 years, the mean uTBS values were similar with no
statistically significant difference between the groups (p = .121). SEM images
showed proper dentin hybridization. Dentin pretreatment with potassium oxalate
did not affect hybrid layer formation, but bond strength decreased over time
after 24 h. Therefore, the clinical use of potassium oxalate to increase dentin
bond durability is not indicated.
PMID- 28401679
TI - The role of cholesterol metabolism and various steroid abnormalities in autism
spectrum disorders: A hypothesis paper.
AB - Based on evidence from the relevant research literature, we present a hypothesis
that there may be a link between cholesterol, vitamin D, and steroid hormones
which subsequently impacts on the development of at least some of the "autisms"
[Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature,
posits that there may be links between cholesterol metabolism, which we will
refer to as "steroid metabolism" and findings of steroid abnormalities of various
kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism
spectrum disorder (ASD). Further research investigating these potential links is
warranted to further our understanding of the biological mechanisms underlying
ASD. Autism Res 2017. (c) 2017 The Authors Autism Research published by Wiley
Periodicals, Inc. on behalf of International Society for Autism Research. Autism
Res 2017, 10: 1022-1044. (c) 2017 International Society for Autism Research,
Wiley Periodicals, Inc.
PMID- 28401680
TI - DNA methylation and its role in the pathogenesis of diabetes.
AB - Although the factors responsible for the recent increase in the prevalence of
diabetes worldwide are not entirely known, the morbidity associated with this
disease results in substantial health and economic burden on society. Epigenetic
modifications, including DNA methylation have been identified as one mechanism by
which the environment interacts with the genome and there is evidence that
alterations in DNA methylation may contribute to the increased prevalence of both
type 1 and type 2 diabetes. This review provides a summary of DNA methylation and
its role in gene regulation, and includes descriptions of various techniques to
measure site-specific and genome-wide DNA methylation changes. In addition, we
review current literature highlighting the complex relationship between DNA
methylation, gene expression, and the development of diabetes and related
complications. In studies where both DNA methylation and gene expression changes
were reported, DNA methylation status had a strong inverse correlation with gene
expression, suggesting that this interaction may be a potential future
therapeutic target. We highlight the emerging use of genome-wide DNA methylation
profiles as a biomarker to predict patients at risk of developing diabetes or
specific complications of diabetes. The development of a predictive model that
incorporates both genetic sequencing and DNA methylation data may be an effective
diagnostic approach for all types of diabetes and could lead to additional
innovative therapies.
PMID- 28401682
TI - Guideline-based intervention to reduce telemetry rates in a large tertiary
centre.
AB - BACKGROUND: Inappropriate cardiac telemetry use is associated with reduced
patient flow and increased healthcare costs. AIM: To evaluate the outcomes of
guideline-based application of cardiac telemetry. METHODS: Phase I involved a
prospective audit (March to August 2011) of telemetry use at a tertiary hospital.
Data were collected on indication for telemetry and clinical outcomes. Phase II
prospectively included patients more than 18 years under general medicine
requiring ward-based telemetry. As phase II occurred at a time remotely from
phase I, an audit similar to phase I (phase II - baseline) was completed prior to
a 3-month intervention (May to August 2015). The intervention consisted of a
daily telemetry ward round and an admission form based on the American Heart
Association guidelines (class I, telemetry indicated; class II, telemetry maybe
indicated; class III, telemetry not indicated). Patient demographics, telemetry
data, and clinical outcomes were studied. Primary endpoint was the percentage
reduction of class III indications, while secondary endpoint included telemetry
duration. RESULTS: In phase I (n = 200), 38% were admitted with a class III
indication resulting in no change in clinical management. A total of 74 patients
was included in phase II baseline (mean +/- standard deviation (SD) age 73 years
+/- 14.9, 57% male), whilst 65 patients were included in the intervention (mean
+/- SD age 71 years +/- 18.4, 35% male). Both groups had similar baseline
characteristics. There was a reduction in class III admissions post-intervention
from 38% to 11%, P < 0.001. Intervention was associated with a reduction in
median telemetry duration (1.8 +/- 1.8 vs 2.4 +/- 2.5 days, P = 0.047); however,
length of stay was similar in both groups (P > 0.05). CONCLUSION: Guideline-based
telemetry admissions and a regular telemetry ward round are associated with a
reduction in inappropriate telemetry use.
PMID- 28401683
TI - A global survey of bacterial type III secretion systems and their effectors.
AB - The type III secretion system (T3SS) is an important genetic determinant that
mediates interactions between Gram-negative bacteria and their eukaryotic hosts.
Our understanding of the T3SS continues to expand, yet the availability of new
bacterial genomes prompts questions about its diversity, distribution and
evolution. Through a comprehensive survey of ~20 000 bacterial genomes, we
identified 174 non-redundant T3SSs from 109 genera and 5 phyla. Many of the
bacteria are environmental strains that have not been reported to interact with
eukaryotic hosts, while several species groups carry multiple T3SSs. Four ultra
conserved Microsynteny Blocks (MSBs) were defined within the T3SSs, facilitating
comprehensive clustering of the T3SSs into 13 major categories, and establishing
the largest diversity of T3SSs to date. We subsequently extended our search to
identify type III effectors, resulting in 8740 candidate effectors. Lastly, an
analysis of the key transcriptional regulators and circuits for the T3SS families
revealed that low-level T3SS regulators were more conserved than higher-level
regulators. This comprehensive analysis of the T3SSs and their protein effectors
provides new insight into the diversity of systems used to facilitate host
bacterial interactions.
PMID- 28401686
TI - Axonal loss in the multiple sclerosis spinal cord revisited.
AB - Preventing chronic disease deterioration is an unmet need in people with multiple
sclerosis, where axonal loss is considered a key substrate of disability.
Clinically, chronic multiple sclerosis often presents as progressive myelopathy.
Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing
disability and has, by inference, been proposed as an indirect index of axonal
degeneration. However, the association between CSA and axonal loss, and their
correlation with demyelination, have never been systematically investigated using
human post mortem tissue. We extensively sampled spinal cords of seven women and
six men with multiple sclerosis (mean disease duration= 29 years) and five
healthy controls to quantify axonal density and its association with
demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno
stained for myelin basic protein and phosphorylated neurofilaments. Measurements
included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter,
(iii) white matter, (iv) demyelination, and the number of axons within the
lateral cortico-spinal tracts. Linear mixed models were used to analyze
relationships. In multiple sclerosis CSA reduction at cervical, thoracic and
lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%)
matter atrophy contributing equally across levels. Axonal density in multiple
sclerosis was lower by 57-62% across all levels and affected all fibers
regardless of diameter. Demyelination affected 24-48% of the gray matter, most
extensively at the thoracic level, and 11-13% of the white matter, with no
significant differences across levels. Disease duration was associated with
reduced axonal density, however not with any area index. Significant association
was detected between focal demyelination and decreased axonal density. In
conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60%
throughout the spinal cord. Spinal cord cross sectional area, reduced by about
20%, appears to be a poor predictor of axonal density.
PMID- 28401684
TI - The Effects of smoking status and smoking history on patients with brain
metastases from lung cancer.
AB - There is limited data on the effects of smoking on lung cancer patients with
brain metastases. This single institution retrospective study of patients with
brain metastases from lung cancer who received stereotactic radiosurgery assessed
whether smoking history is associated with overall survival, local control, rate
of new brain metastases (brain metastasis velocity), and likelihood of neurologic
death after brain metastases. Patients were stratified by adenocarcinoma versus
nonadenocarcinoma histologies. Kaplan-Meier analysis was performed for survival
endpoints. Competing risk analysis was performed for neurologic death analysis to
account for risk of nonneurologic death. Separate linear regression and
multivariate analyses were performed to estimate the brain metastasis velocity.
Of 366 patients included in the analysis, the median age was 63, 54% were male
and, 60% were diagnosed with adenocarcinoma. Current smoking was reported by 37%
and 91% had a smoking history. Current smoking status and pack-year history of
smoking had no effect on overall survival. There was a trend for an increased
risk of neurologic death in nonadenocarcinoma patients who continued to smoke
(14%, 35%, and 46% at 6/12/24 months) compared with patients who did not smoke
(12%, 23%, and 30%, P = 0.053). Cumulative pack years smoking was associated with
an increase in neurologic death for nonadenocarcinoma patients (HR = 1.01, CI:
1.00-1.02, P = 0.046). Increased pack-year history increased brain metastasis
velocity in multivariate analysis for overall patients (P = 0.026). Current
smokers with nonadenocarcinoma lung cancers had a trend toward greater neurologic
death than nonsmokers. Cumulative pack years smoking is associated with a greater
brain metastasis velocity.
PMID- 28401685
TI - Characterization of new bone morphogenetic protein (Bmp)-2 regulatory alleles.
AB - Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical
morphogen; a molecule that acts at a distance and whose concentration influences
cell proliferation, differentiation, and apoptosis. Key events requiring precise
Bmp2 regulation include heart specification and morphogenesis and neural
development. In mesenchymal cells, the concentration of BMP2 influences
myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount,
timing, and location of BMP2 synthesis influence pattern formation and
organogenesis, the mechanisms that regulate Bmp2 are crucial. A sequence within
the 3'UTR of the Bmp2 mRNA termed the "ultra-conserved sequence" (UCS) has been
largely unchanged since fishes and mammals diverged. Cre-lox mediated deletion of
the UCS in a reporter transgene revealed that the UCS may repress Bmp2 in
proepicardium, epicardium, and epicardium-derived cells (EPDC) and in tissues
with known epicardial contributions (coronary vessels and valves). The UCS also
repressed the transgene in the aorta, outlet septum, posterior cardiac plexus,
cardiac and extra-cardiac nerves, and neural ganglia. We used homologous
recombination and conditional deletion to generate three new alleles in which the
Bmp2 3'UTR was altered as follows: a UCS flanked by loxP sites with or without a
neomycin resistance targeting vector, or a deleted UCS. Deletion of the UCS was
associated with elevated Bmp2 mRNA and BMP signaling levels, reduced fitness, and
embryonic malformations.
PMID- 28401687
TI - Effectiveness of interventions to promote physical activity and/or decrease
sedentary behaviour among rural adults: a systematic review and meta-analysis.
AB - Physical inactivity and overweight and obesity are more prevalent among rural
than urban populations. This study aimed to review published evidence of the
effectiveness of interventions to increase physical activity (PA) and/or decrease
sedentary behaviour (SB) among rural adults and to identify factors associated
with effectiveness. Seven electronic databases were searched for controlled
trials of a PA or SB intervention. Meta-analysis was conducted using random
effects models and meta-regression. Thirteen studies were included in the
qualitative synthesis (n = 4,848 participants) and 12 in the meta-analysis (n =
4,820). All studies were interventions to increase PA. Overall, there was no
effect on PA (standardized mean difference [SMD] 0.11; 95% confidence interval
[CI] -0.04, 0.25) or SB (SMD 0.07; 95% CI -0.33, 0.20). In PA subgroup analyses,
studies employing objective outcome measures demonstrated effects in favour of
the intervention (SMD 0.65, 95% CI 0.30, 1.00), while those using self-reported
measures did not (SMD 0.00; 95% CI -0.11, 0.10). This review highlights
significant gaps in our understanding of how best to promote PA and reduce SB
among rural adults. Future studies should use objective measures of PA as study
outcomes. The absence of interventions to decrease SB is of concern, with
immediate action required to address this large knowledge gap.
PMID- 28401688
TI - Goals of patient care system change with video-based education increases rates of
advance cardiopulmonary resuscitation decision-making and discussions in
hospitalised rehabilitation patients.
AB - BACKGROUND: Advance cardiopulmonary resuscitation (CPR) discussions and decision
making are not routine clinical practice in the hospital setting. Frail older
patients may be at risk of non-beneficial CPR. AIM: To assess the utility and
safety of two interventions to increase CPR decision-making, documentation and
communication for hospitalised older patients. METHODS: A pre-post study tested
two interventions: (i) standard ward-based education forums with CPR content; and
(ii) a combined, two-pronged strategy with 'Goals of Patient Care' (GoPC) system
change and a structured video-based workshop; against usual practice (i.e. no
formal training). Participants were a random sample of patients in a hospital
rehabilitation unit. The outcomes were the proportion of patients documented as:
(i) not for resuscitation (NFR); and (ii) eligible for rapid response team (RRT)
calls, and rates of documented discussions with the patient, family and carer.
RESULTS: When compared with usual practice, patients were more likely to be
documented as NFR following the two-pronged intervention (adjusted odds ratio
(aOR): 6.4, 95% confidence interval (CI): 3.0; 13.6). Documentation of
discussions with patients was also more likely (aOR: 3.3, 95% CI:1.8; 6.2).
Characteristics of patients documented NFR were similar between the phases, but
were more likely for RRT calls following Phase 3 (P 0.03). CONCLUSION: An
increase in advance CPR decisions occurred following GoPC system change with
education. This appears safe as NFR patients had the same level of frailty
between phases but were more likely to be eligible for RRT review. Increased
documentation of discussions suggests routine use of the GoPC form may improve
communication with patients about their care.
PMID- 28401689
TI - Progressive resistance training (PRT) improves rheumatoid arthritis outcomes: A
district general hospital (DGH) model.
AB - OBJECTIVE: Rheumatoid cachexia is common in rheumatoid arthritis (RA) patients
and develops soon after diagnosis, despite adequate drug therapy. It is
associated with multiple adverse effects on body composition, function and
mortality. Progressive resistance training (PRT) improves these outcomes but is
not widely prescribed outside of a research setting. The aim of the present study
was to explore the practicality and effectiveness of providing PRT to patients in
a district general hospital within the constraints of existing resources.
METHODS: Patients attending a rheumatology clinic were invited to participate in
a weekly PRT class for 6 weeks, supervised by a physiotherapist. Outcome measures
included: body composition measures (waist and hip circumference, weight,
percentage body fat); functional measures (grip strength, 60-s sit-to-stand test,
single leg stance, Health Assessment Questionnaire); mood; fatigue and disease
activity measures (sleep scale, hospital anxiety and depression scale, Functional
Assessment of Chronic Illness Therapy, pain visual analogue scale). These were
measured at baseline and at 6 weeks. RESULTS: A total of 83 patients completed
the programme (60% female, mean age 51.2 years), of whom 34.9% had early RA.
Improvements were seen in multiple measures inpatients with early RA and with
established inflammatory arthritis, and were not affected by age or gender.
CONCLUSIONS: Patients with early and established inflammatory arthritis alike
benefited from a 6-week PRT programme provided within a National Health Service
setting. Although further work is needed to look at long-term effects, we suggest
that this intervention should be more widely available.
PMID- 28401690
TI - Oxygen and the activity and distribution of marine Thaumarchaeota.
PMID- 28401692
TI - 47th Annual Scientific Meeting of the Australian and New Zealand Society of
Nuclear Medicine Hobart, Tasmania, 21-23 Apr 2017 Evidence and Outcomes.
PMID- 28401691
TI - Biocatalysis as a green route for recycling the recalcitrant plastic polyethylene
terephthalate.
AB - Biocatalysis can enable a closed-loop recycling of post-consumer PET waste.
PMID- 28401693
TI - Extending the assessment of patient-centredness in health care: Development of
the updated Valuing Patients as Individuals Scale using exploratory factor
analysis.
AB - AIMS AND OBJECTIVES: To update and re-validate the Valuing Patients as
Individuals Scale for use as a patient appraisal of received healthcare.
BACKGROUND: Healthcare in the United Kingdom and beyond is required to deliver
high quality, person-centred care that is clinically effective and safe. However,
patient experience is not uniform, and complaints often focus on the way patients
have been treated. Legislation in United Kingdom requires health services to
gather and use patients' evaluations of care to improve services. DESIGN: This
study uses scoping literature reviews, cognitive testing of questionnaire items
with patient and healthcare staff focus groups, and exploratory factor analysis.
METHODS/SETTING/PARTICIPANTS: Data were collected from 790 participants across 34
wards in two acute hospitals in one National Health Service Health Board in
Scotland from September 2011-February 2012. Ethics and Research and Development
approval were obtained. RESULTS: Fifty six unique items identified through
literature review were added to 72 original Valuing Patients as Individuals Scale
items. Face validity interviews removed ambiguous or low relevance items leaving
88 items for administration to patients. Two hundred and ninety questionnaires
were returned, representing 37% response rate, 71 were incomplete. Thus 219
complete data were used for Exploratory Factor Analysis with varimax orthogonal
rotation. This revealed a 31 item, three factor solution, Care and Respect;
Understanding and Engagement; Patient Concerns, with good reliability, concurrent
and discriminant validity in terms of gender. A shortened 10 item measure based
on the top 3 or 4 loading items on each scale was comparable. CONCLUSIONS: The
Updated Valuing Patients as Individuals Scale is sufficiently developed to
capture patient appraisals of received care. RELEVANCE TO CLINICAL PRACTICE: The
short scale version is now being routinized in real-time evaluation of patient
experience contributing to this United Kingdom, National Health Service setting
meeting its policy and legislative requirements.
PMID- 28401694
TI - Effects of grazing, phosphorus and light on the growth rates of major
bacterioplankton taxa in the coastal NW Mediterranean.
AB - Estimation of growth rates is crucial to understand the ecological role of
prokaryotes and their contribution to marine biogeochemical cycling. However,
there are only a few estimates for individual taxa. Two top-down (grazing) and
bottom-up (phosphorus (P) availability) manipulation experiments were conducted
under different light regimes in the NW Mediterranean Sea. Growth rate of
different phylogenetic groups, including the Bacteroidetes, Rhodobacteraceae,
SAR11, Gammaproteobacteria and its subgroups Alteromonadaceae and the NOR5/OM60
clade, were estimated from changes in cell numbers. Maximal growth rates were
achieved in the P-amended treatments but when comparing values between treatments
(response ratios), the response to predation removal was in general larger than
to P-amendment. The Alteromonadaceae displayed the highest rates in both
experiments followed by the Rhodobacteraceae, but all groups largely responded to
filtration and P-amendment, even the SAR11 which presented low growth rates.
Comparing light and dark treatments, growth rates were on average equal or higher
in the dark than in the light for all groups, except for the Rhodobacteraceae and
particularly the NOR5 clade, groups that contain photoheterotrophic species.
These results are useful to evaluate the potential contributions of different
bacterial types to biogeochemical processes under changing environmental
conditions.
PMID- 28401695
TI - Case-based discussion: perceptions of feedback.
AB - BACKGROUND: Over recent years there has been a trend towards developing high
quality assessments to assess a doctor's performance in the workplace. Case-based
discussion (CbD) is a form of workplace-based assessment that has the potential
to provide feedback to trainees on their performance or management of a specific
case. The aim of this study was to explore how CbDs are perceived and implemented
in practice amongst a UK cohort of medical trainees. METHODS: This study involved
78 medical trainees at a UK hospital completing a questionnaire rating their last
CbD experience, including the duration spent receiving feedback, whether it was
pre-planned or ad hoc and how they responded to the feedback received. Focus
groups were conducted involving 12 trainees to discuss common themes on feedback
arising from the questionnaire, and thematic analysis was carried out following
these discussions. RESULTS: Only 19 per cent of assessments were pre-planned and
the average duration of assessments was 6-10 minutes, with feedback lasting less
than 5 minutes. A total of 76 per cent of trainees responded to the feedback they
received by completing self-directed learning or by addressing the specific
action points arising from the feedback. The focus groups highlighted the
barriers to incorporating these assessments into everyday practice, including
appreciating the time constraints and the importance of trainer engagement in the
assessment process. The aim of this study was to explore how CbDs are perceived
and implemented in practice CONCLUSION: This study demonstrates that most
trainees appreciate the educational value of CbDs, but more emphasis and training
is required in planning these assessments and in providing feedback that is both
specific and actionable.
PMID- 28401696
TI - Understanding the Crystal Packing and Organic Thin-Film Transistor Performance in
Isomeric Guest-Host Systems.
AB - In order to understand how additives influence the structure and electrical
properties of active layers in thin-film devices, a compositionally identical but
structurally different guest-host system based on the syn and anti isomers of
triethylsilylethynyl anthradithiophene (TES ADT) is systematically explored. The
mobility of organic thin-film transistors (OTFTs) comprising anti TES ADT drops
with the addition of only 0.01% of the syn isomer and is pinned at the mobility
of OTFTs having pure syn isomer after the addition of only 10% of the isomer. As
the syn isomer fraction increases, intermolecular repulsion increases, resulting
in a decrease in the unit-cell density and concomitant disordering of the charge
transport pathway. This molecular disorder leads to an increase in charge
trapping, causing the mobility of OTFTs to drop with increasing syn-isomer
concentration. Since charge transport is sensitive to even minute fractions of
molecular disorder, this work emphasizes the importance of prioritizing
structural compatibility when choosing material pairs for guest-host systems.
PMID- 28401697
TI - Establishment of novel therapy to reduce progression of myopia in rats with
experimental myopia by fibroblast transplantation on sclera.
AB - Myopia is one of the most common visual disorders, and is characterized by a
progressive axial elongation of the eye. Several methods have been tried to
reduce the progression of axial elongation and myopia, but there are still no
well-accepted procedures. We hypothesized that transplantation of fibroblasts on
the sclera would lead to the synthesis of collagen fibrils on the sclera and
reinforce it, and reduce the degree of axial elongation of eyes with form
deprivation myopia. To examine this, we developed a form deprivation myopia model
in albino Wistar rats and examined the effects of human fibroblasts (hFbs)
transplantation on the sclera in the progression of myopia and axial elongation.
We found that the form deprivation by eyelid suture induced a myopic shift and
axial elongation associated with a thinner sclera and smaller-diameter collagen
fibrils in Wistar rats. We also found that the transplanted hFbs synthesized type
1 collagen fibrils on the rat sclera, and these eyes with form deprivation had
significantly reduced ocular elongation and myopic shift than the eyes without
hFbs transplantation. Some of the synthesized collagen fibrils migrated into the
sclera and had a bundle-like appearance and a stripe-like pattern, indicating
they had mature characteristics. These findings suggest that the rat sclera was
reinforced by the newly synthesized collagen fibrils and the axial elongation was
reduced. These results can provide important information for the development of a
therapy targeting myopia in humans. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28401698
TI - Whoever shouts the loudest: Listening to parents of children with disabilities.
AB - BACKGROUND: Elevated stress is common among parents of children with
disabilities. The parents' perspective and evaluation of services have a
significant impact on their well-being and adaptation to their child's disability
and is a source of information for service improvements. This study explores
parental perceptions of communication and collaboration between parents and
health and education staff in the context of an imminent reconfiguration of
disability services. METHODS: A qualitative study was conducted using four focus
groups with parents (n = 24) of children with disabilities who attend various
educational and health services. RESULTS: Thematic analysis revealed five key
themes: Us versus them, lack of child/family centeredness, resources, keyworker
and uncertain access to a complex system. CONCLUSIONS: Parents want greater
collaboration between parents and professionals. They identified a keyworker as a
potential solution to the current system that is not child-centred. This would
also lessen the burden associated with high levels of advocacy.
PMID- 28401699
TI - Sling, Scoop, and Squirter: Anatomical Features Facilitating Prey Transport,
Processing, and Swallowing in Rorqual Whales (Mammalia: Balaenopteridae).
AB - Much is known about lunge feeding in balaenopterid whales, but many key aspects
of structure, function, and behavior have not yet been explained in detail,
especially with regard to concentrating, positioning, and swallowing large
aggregations of prey. We describe a novel system of three integrated structural
components, all of which are involved in sequential feeding activities (intraoral
transport, filtration, and swallowing of prey) that follow lunge-feeding
engulfment of prey-laden water in rorquals: (1) a hammock-like muscular sling
comprising extrinsic lingual musculature along the midline of the ventral pouch;
(2) the flattened scoop-like arrangement of caudal-most baleen plates converging
in the oropharynx adjacent to the esophageal opening; and (3) a flow-diverting
flange at the posterior dorsum of the lip, by a flow channel at the angle of the
mouth. Subsequent to contraction of the ventral pouch and concomitant expulsion
of the mouthful of ingested water, these three structures together, we contend,
aid in (1) channeling prey posteriorly toward the esophageal opening; (2)
concentrating prey as excess water is squeezed from (what is presumed to be) the
slurry-like mixture of nektonic and/or planktonic prey and water; and (3) guiding
prey into the isthmus of the fauces while simultaneously (4) facilitating
expulsion of water. These related functions occur along with, and are in part
achieved by, elevation and retraction of the tongue and oral floor. Given their
presumed functional role, these systems are best described as a suite of
integrated structural adaptations. Anat Rec, 2017. (c) 2017 Wiley Periodicals,
Inc. Anat Rec, 300:2070-2086, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28401700
TI - Silica immobilization of Geobacter sulfurreducens for constructing ready-to-use
artificial bioelectrodes.
AB - Microbial electrochemical technologies (METs) rely on the control of interactions
between microorganisms and electronic devices, enabling to transform chemical
energy into electricity. We report a new approach to construct ready-to-use
artificial bioelectrodes by immobilizing Geobacter sulfurreducens cells in
composite materials associating silica gel and carbon felt fibres. Viability test
confirmed that the majority of bacteria (ca. 70 +/- 5%) survived the
encapsulation process in silica and that cell density did not increase in 96 h.
The double entrapment within the silica-carbon composite prevented bacterial
release from the electrode but allowed a suitable mass transport (ca. 5 min after
electron donor pulse), making the electrochemical characterization of the system
possible. The artificial bioelectrodes were evaluated in three-electrode reactors
and the maximum current displayed was ca. 220 and 150 MUA cm-3 using acetate and
lactate as electron donors respectively. Cyclic voltammetry of acetate-fed
bioelectrodes revealed a sigmoidal catalytic oxidation wave, typical of more
advanced-stage biofilms. The presence of G. sulfurreducens within composites was
ascertained by SEM analysis, suggesting that only part of the bacterial
population was in direct contact with the carbon fibres. Preliminary analyses of
the transcriptomic response of immobilized G. sulfurreducens enlightened that
encapsulation mainly induces an osmotic stress to the cells. Therefore, ready-to
use artificial bioelectrodes represent a versatile time- and cost-saving strategy
for microbial electrochemical systems.
PMID- 28401702
TI - Confirmatory factor analysis of the Sleep Disturbance Scale for Children (SDSC)
in a clinical sample of children and adolescents.
AB - The Sleep Disturbance Scale for Children was developed as a parent-report measure
to screen for sleep disturbances within the preceding 6 months. Notably, the
scale was developed using a sample of typically developing children and children
with sleep disorders. The aim of this study was to factor analyse the Sleep
Disturbance Scale for Children using a clinical sample of children with a range
of neuropsychological conditions and co-morbidities, and determine whether the
original six-factor structure was retained. Four-hundred and sixteen children
aged 5-17 years were assessed at the Neurosciences Unit (Perth, Western
Australia) as part of routine, clinical neuropsychological assessment. Parents
and guardians also completed the Sleep Disturbance Scale for Children to rate
their child's sleep. Confirmatory factor analysis of the original Sleep
Disturbance Scale for Children model (Bruni et al. J. Sleep Res., 1996, 5: 251
261) revealed a less than ideal fit. Three adjustments were made to the model
based on factor loadings and modification indices. The sleep hyperhidrosis factor
(including items 9 and 16) along with item 10 was removed, leaving a five-factor
Sleep Disturbance Scale for Children model. The five-factor model (Sleep
Disturbance Scale for Children-R) was factor analysed, and examination of model
fit statistics indicated that this new model produced good fit. Additional
analyses revealed that older children had greater difficulty falling and staying
asleep, and with daytime sleepiness. However, no significant differences were
observed across gender, diagnosis or socioeconomic status. The results of this
study suggest that the Sleep Disturbance Scale for Children-R may be a more
appropriate measure when assessing clinical samples. However, further research is
required to validate the Sleep Disturbance Scale for Children-R against objective
measures of sleep and to determine appropriate t-score cut-offs.
PMID- 28401701
TI - Presence of bone marrow micro-metastases in stage I-III colon cancer patients is
associated with worse disease-free and overall survival.
AB - The prognostic significance of bone marrow micro-metastases (BMM) in colon cancer
patients remains unclear. We conducted a prospective cohort study with long-term
follow-up to evaluate the relevance of BMM as a prognostic factor for disease
free (DFS) and overall survival (OS) in stage I-III colon cancer patients. In
this prospective multicenter cohort study 144 stage I-III colon cancer patients
underwent bone marrow aspiration from both iliac crests prior to open oncologic
resection. The bone marrow aspirates were stained with the pancytokeratin
antibody A45-B/B3 and analyzed for the presence of epithelial tumor cells. DFS
and OS were analyzed using a Cox proportional hazard model and robust standard
errors to account for clustering in the multicenter setting. Median overall
follow-up was 6.2 years with no losses to follow-up, and 7.3 years in patients
who survived. BMM were found in 55 (38%) patients. In total, 30 (21%) patients
had disease recurrence and 56 (39%) patients died. After adjusting for known
prognostic factors, BMM positive patients had a significantly worse DFS (hazard
ratio [HR] 1.33; 95% confidence interval [95% CI]: 1.02-1.73; P = 0.037) and OS
(HR 1.30; 95% CI: 1.09-1.55; P = 0.003) compared to BMM negative patients. Bone
marrow micro-metastases occur in over one third of stage I-III colon cancer
patients and are a significant, independent negative prognostic factor for DFS
and OS. Future trials should evaluate whether node-negative colon cancer patients
with BMM benefit from adjuvant chemotherapy.
PMID- 28401703
TI - Tacrolimus population pharmacokinetics according to CYP3A5 genotype and clinical
factors in Chinese adult kidney transplant recipients.
AB - WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic
index and a considerable inter- and intraindividual pharmacokinetic variability.
The aim of our study was to develop a population pharmacokinetic model of
tacrolimus in adult kidney transplant of Chinese patients, identify factors
especially CYP3A5*3 genetic polymorphism that explain variability, and determine
dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney
transplant patients treated with tacrolimus were determined using polymerase
chain reaction-restriction fragment length polymorphism analysis. Trough blood
concentration data were collected from all of the patients during the 12 months
of post-transplantation days and were analysed using the nonlinear mixed-effects
modelling program. After building the final model, 1000 bootstraps were performed
to validate the final model. RESULTS AND DISCUSSION: A one-compartment model with
first-order absorption and elimination adequately described the pharmacokinetics
of tacrolimus. In this study, we observed that POD, HCT and CYP3A5*3 genotype
were determinant factors in CL/F and POD related with V/F of tacrolimus
significantly. The final model with the clearance covariates was presented as:
Cl/F=THETA(1)*EXP(THETA(4)*(83/POD))*(39.1/HCT)**THETA(5)*EXP(THETA(6)*CYP3A5),
and the final model with the volume covariates was presented as:
Vd/F=THETA(2)*POD**THETA(3). The Ka was fixed to 4.5 h-1 . WHAT IS NEW AND
CONCLUSION: The HCT, CYP3A5*3 genetic polymorphism and POD contributed to the
interindividual variability of oral tacrolimus in Chinese adult renal transplant
patients.
PMID- 28401705
TI - A 3D virtual reality ophthalmoscopy trainer.
AB - BACKGROUND: Performing eye examinations is an important clinical skill that
medical students often find difficult to become proficient in. This paper
describes the development and evaluation of an innovative 3D virtual reality (VR)
training application to support learning these skills. METHODS: The VR
ophthalmoscope was developed by a clinical team and technologist using the unity
game engine, smartphone and virtual reality headset. It has a series of tasks
that include performing systematic eye examinations, identifying common eye
pathologies and a knowledge quiz. As part of their clinical training, 15 fourth
year medical students were surveyed for their views on this teaching approach.
The Technology Acceptance Model was used to evaluate perceived usefulness and
ease of use. Data were also collected on the usability of the app, together with
the students' written comments about it. RESULTS: Users agreed that the teaching
approach improved their understanding of ophthalmoscopy (n = 14), their ability
to identify landmarks in the eye (n = 14) and their ability to recognise
abnormalities (n = 15). They found the app easy to use (n = 15), the teaching
approach informative (n = 13) and that it would increase students' confidence
when performing these tasks in future (n = 15). Performing eye examinations is an
important clinical skill DISCUSSION: The evaluation showed that a VR app can
successfully simulate the processes involved in performing eye examinations. The
app was highly rated for all elements of perceived usefulness, ease of use and
usability. Medical students stated that they would like to be taught other
medical skills in this way in future.
PMID- 28401706
TI - For what do we stand?
PMID- 28401704
TI - HIF-1alpha binding to AEG-1 promoter induced upregulated AEG-1 expression
associated with metastasis in ovarian cancer.
AB - Ovarian cancer with the highest mortality rate among gynecological malignancies
is one of common cancers among female cancer patients. As reported in recent
years, AEG-1 was associated with the occurrence, development, and metastasis of
ovarian cancer, but the mechanisms remain unclear. In the current study, invasion
capabilities of ovarian cancer OVCAR3 cells were measured by viral infection and
transwell assay. Western blot analysis was used to evaluate the expression levels
of beta-catenin, E-cadherin, MMP2, and MMP9. With qRT-PCR analysis, AEG-1 and HIF
1alpha gene expression were detected. We used luciferase reporter gene to measure
AEG-1 promoter activity under normoxia/hypoxia in OVCAR3 cells. Our work
demonstrated that AEG-1 significantly enhanced invasion capabilities of OVCAR3
cells and the expression levels of beta-catenin, E-cadherin, MMP2, and MMP9
associated with invasion capabilities of OVCAR3 cells were upregulated.
Furthermore, hypoxia enhanced invasion capabilities of OVCAR3 cells and induced
AEG-1 high gene expression, which was reversed by AEG-1 knockdown lentivirus. HIF
1alpha expression upregulation was induced in OVCAR3 cells after hypoxia. HIF
1alpha knockdown lentivirus induced downregulated expression of AEG-1 and
invasion capabilities of OVCAR3 cells were also inhibited. Wild-type AEG-1
promoter activity under hypoxic conditions was significantly higher than that AEG
1 mutation under normoxic conditions in the absence of hypoxia response. Our
results suggested that HIF-1alpha binds to AEG-1 promoter to upregulate its
expression, which was correlated with metastasis in ovarian cancer by inducing
the expression of MMP2 and MMP9 as well as inhibiting expression of E-cadherin
and beta-catenin.
PMID- 28401707
TI - Myxobacteria in high moor and fen: An astonishing diversity in a neglected
extreme habitat.
AB - Increasing antibiotic resistances of numerous pathogens mean that myxobacteria,
well known producers of new antibiotics, are becoming more and more interesting.
More than 100 secondary metabolites, most of them with bioactivity, were
described from the order Myxococcales. Especially new myxobacterial genera and
species turned out to be reliable sources for novel antibiotics and can be
isolated from uncommon neglected habitats like, for example, acidic soils. Almost
nothing is known about the diversity of myxobacteria in moors, except some
information from cultivation studies of the 1970s. Therefore, we evaluated the
myxobacterial community composition of acidic high moor and fen both with
cultivation-independent 16S rRNA clone bank analysis and with cultivation.
Phylogenetic analyses of clone sequences revealed a great potential of
undescribed myxobacteria in high moor and fen, whereby all sequences represent
unknown taxa and were detected exclusively by cultivation-independent analyses.
However, many clones were assigned to sequences from other cultivation
independent studies of eubacterial diversity in acidic habitats. Cultivation
revealed different strains exclusively from the genus Corallococcus. Our study
shows that the neglected habitat moor is a promising source and of high interest
with regard to the cultivation of prospective new bioactive secondary metabolite
producing myxobacteria.
PMID- 28401708
TI - How Veterans Health Administration Suicide Prevention Coordinators Assess Suicide
Risk.
AB - : This cross-sectional study was designed to examine the suicide risk assessment
practices of Suicide Prevention Coordinators (SPCs) within the Veterans Health
Administration. Specifically, this study sought to (1) identify factors SPCs
consider most important in assessing risk and patient priority; (2) measure the
level of consistency and agreement between SPCs in assessing suicide risk and
prioritizing cases; and (3) measure individual SPC consistency between cases.
SPCs (n = 63) responded to online survey questions about imminent and prolonged
risk for suicide in response to 30 fictional vignettes. Combinations of 12 acute
and chronic suicide risk factors were systematically distributed throughout the
30 vignettes using the Fedorov () procedure. The SPCs were also asked to identify
the level of priority for further assessment both disregarding and assuming
current caseloads. Data were analysed using clinical judgement analysis. Suicidal
plan, beta = 1.64; 95% CI (1.45, 1.82), and preparatory behaviour, beta = 1.40;
95% CI (1.23, 1.57), were considered the most important acute or imminent risk
factors by the SPCs. There was less variability across clinicians in the
assessment of risk when alcohol use (p = 0.02) and hopelessness (p = 0.03) were
present. When considering acute or imminent risk factors, there was considerable
variability between clinicians on a vignette-by-vignette basis, median SD = 0.86
(range = 0.47, 1.13), and within individual clinicians across vignettes, median
R2 = 0.80 (0.49, 0.95). These findings provide insight into how this group of
providers think about acute and chronic risk factors contributing to imminent
suicide risk in Veterans. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY
PRACTITIONER MESSAGE: Identifies factors that practitioners consider most
important in suicide risk assessment Discusses how to distinguish between chronic
and acute risk for suicide Identifies factors that lead to more consistent
clinical judgments.
PMID- 28401709
TI - The role of microRNA-93 regulating angiopoietin2 in the formation of malignant
pleural effusion.
AB - The biological roles of miRNAs in the development of malignant pleural effusion
(MPE) are unclear. In this study, the miRNA microarray analysis was performed in
two different prognosis groups of lung adenocarcinoma patients. Expression
profiles of miRNAs in MPEs were identified. With the help of quantification PCR,
we confirmed the expression differences of miRNAs and further analyzed their
biological functions and relative target genes in vitro. The target gene of miR
93 was estimated by online database, and also, the protein was tested. The target
gene and the binding sites of specific miRNA were estimated by online database.
The combining capacity of binding sites was verified by luciferase reporter gene
assay, and the target gene protein was tested by western blot. We detected 107
miRNAs with expression differences (n = 10) and confirmed significant expression
differences in miR-93 and miR-146a in two groups of patients (n = 84). By
manipulating miR-93 expression of human lymphatic endothelial cells (HLEC) and
human umbilical vein endothelial cells (HUVEC), we discovered that high
expression of miR-93 inhibited migration, proliferation, and angiogenesis. And
also, miR-93 increased not only apoptosis, but also G1 phase cell block. By using
luciferase reporter gene assay and western blot, we confirmed that angiopoietin2
(Ang2) was the target of miR-93. The data showed that miR-93 has an inhibiting
effect on pleural effusion. By targeting Ang2, miR-93 regulates angiogenesis and
lymphangiogenesis and plays a role in pathogenetic mechanism of MPE. MiR-93/Ang2
may shed light on potential new targets in cancer treatment.
PMID- 28401710
TI - Threshold value of LIAISON XL anti-HCV screening assay predicting positive
immunoblotting results.
AB - Some international guidelines recommend evaluating the need to confirm positive
anti-hepatitis C virus (HCV) antibody screening results by means of a more
specific antibody or molecular biology test on the basis of a screening threshold
value (such as the sample signal/cut-off ratio) that can predict the positivity
of additional antibody testing in at least 95% of cases. The aim of this study
was to determine the threshold value of the DiaSorin LIAISON XL chemiluminescence
test. Two hundred and twenty-eight routine laboratory samples that were
chemiluminescence positive for anti-HCV antibodies but had different signal/cut
off ratios were assayed using immunoblotting, which indicated that 155 (68.0%)
were positive, 40 (17.5%) were negative, and 33 (14.5%) were indeterminate. When
the samples were divided on the basis of their signal/cut-off ratios, 95.5% of
the samples with a ratio of >=3.5 were positive as against 74.1% of the positive
or indeterminate samples with a ratio of <3.5. Statistical analysis using
Youden's index and a receiver operating characteristic curve showed that the
optimum cut-off value was 3.65. These findings indicate that, when using the
LIAISON XL system for anti-HCV antibody screening, a signal/cut-off ratio of
>=3.65 makes further confirmatory tests unnecessary.
PMID- 28401711
TI - Screening for subclinical subclavian artery stenosis before coronary artery
bypass grafting: Should we do it?
AB - Atherosclerotic subclavian artery disease is detected in about 5% of patients
referred for coronary artery bypass (CABG) surgery. The internal mammary artery,
a branch of the subclavian artery, is the most frequently utilized graft to
restore coronary circulation because of its longevity. Stenosis or occlusion of
the subclavian artery can cause retrograde blood flow in the ipsilateral internal
mammary artery, known as "steal," compromising coronary circulation supplied by
the graft. Steal may be asymptomatic or may result in symptoms of myocardial
ischemia. Symptomatic subclavian artery stenosis post bypass is referred to as
coronary subclavian steal syndrome post-CABG. The incidence is not well defined,
and the benefits of screening patients referred for CABG are not known. Despite
the various modalities available to detect subclavian artery stenosis, current
guidelines fail to provide guidance about screening high-risk patients for this
entity. Detection of subclavian artery disease prior to CABG can reduce
complications posed by post-mammary artery graft cardiac ischemia. This review
discusses the utility of preoperative subclavian artery screening prior to CABG.
PMID- 28401712
TI - Pantoprazole-induced hypomagnesaemia causing cerebellar syndrome and seizures.
PMID- 28401713
TI - Cultural competence and over-investigation.
PMID- 28401714
TI - An audit of patients with mature T-cell non-Hodgkin lymphoma by transplant status
in Tasmania.
AB - This retrospective audit of patients diagnosed with mature T-cell lymphoma across
a 10-year period provides contemporary information on the outcomes and treatment
patterns of an Australian cohort. Forty-two patients diagnosed with mature T-cell
lymphoma were identified from the Tasmanian Cancer Registry and analysed using
medical records and simple statistical analysis. The demographics and outcomes of
patients in this cohort were comparable to large international studies with
treatment patterns in line with the best available evidence.
PMID- 28401715
TI - An appeal to the medical community: the need for laboratory specialist input in
the development of clinical practice guidelines.
PMID- 28401716
TI - Prescribing and medication communication on the post-take ward round.
AB - Gaps in communication between medical officers and poor planning are associated
with prescribing errors and may result in patient harm. This study describes
medication communication on post-take ward rounds (PTWR). Over 6 weeks on 24
PTWR, 130 patients, prescribed 1244 medications, were observed. Of these, 811
(65%) medications were discussed, with 249 discussions (relating to 126
medications) being 'in-depth'. Of 191 planned medication-related actions, 38
(20%) were not implemented by the end of the PTWR and 21 (11%) by time of
discharge from hospital. This study suggests that the level of medication
communication and subsequent actions are suboptimal. Processes to improve this
situation should be explored.
PMID- 28401717
TI - Variation in dispensing of opioid analgesics in Australia.
PMID- 28401718
TI - Compliance to clinical pathways in the management of suspected pulmonary embolus:
are there cost implications?
AB - This study investigated the cost implications of poor compliance to established
guidelines for management of suspected pulmonary embolism (PE) in two NSW public
hospitals. A retrospective audit showed that the prevalence of PE overall was
9.9% (4.3% in the low-risk groups) in 436 patients. An estimated total of $32 454
(14%) was spent on unnecessary tests.
PMID- 28401720
TI - Corrigendum.
PMID- 28401719
TI - Hepatitis A to E: what's new?
AB - Viral hepatitis contributes to significant morbidity and mortality worldwide.
While acute infection may be self-limiting, unrecognised chronic infection and
under-utilisation of guideline-based approaches to therapy contribute to
increasing rates of cirrhosis, hepatocellular carcinoma and death. Our aim was to
review the current evidence for screening, diagnosis and treatment in hepatitis A
to E. Evidence for this review was sourced from international and Australian
guidelines and high-quality clinical trials. MEDLINE was searched using
structured key word strategy and retrieved articles were reviewed methodically to
inform a brief and up-to-date synopsis of hepatitis A to E. We share some of the
recent developments in viral hepatitis, specifically the new therapies for
hepatitis C. Direct-acting antiviral therapies are safe, well-tolerated and
effective. Subsidies allow access for all Australians with most strains of
hepatitis C. We outline evidence underpinning efficacy and safety of treatment
for hepatitis B, while clarifying some of the nuances in the setting of pregnancy
and immunosuppression. We provide a simplified concept to facilitate
understanding of the five phases of hepatitis B; practical for real-world
setting. Hepatitis A to E is a broad topic, not all aspects of these viruses can
be covered in this short review. We provided suggestions for evidence based
guidelines, which are a suitable supplement to this article.
PMID- 28401721
TI - Medical colleges: whose purpose, if any, do they serve? A response.
PMID- 28401722
TI - Double fire tachycardia induced cardiomyopathy: first ever reported case in
Australia.
PMID- 28401723
TI - The clinical academic workforce in Australia and New Zealand: report on the
second binational summit to implement a sustainable training pathway.
AB - There has been a decline in the proportion of clinical academics compared with
full-time clinicians, since 2004. A Working Party was established to help develop
and implement a model for the training of clinical academics. After a highly
successful first summit in 2014 that summarised the challenges faced by clinical
academics in Australia and New Zealand, a second summit was convened late in 2015
to report on progress and to identify key areas for further action. The second
summit provided survey results that identified the varied training pathways
currently offered to clinical academics and the institutions willing to be
involved in developing improved pathways. A literature review also described the
contributions that clinical academics make to the health sector and the
challenges faced by this workforce sector. Current training pathways created for
clinical academics by Australasian institutions were presented as examples of
what can be done. The perspectives of government and research organisations
presented at the summit helped define how key stakeholders can contribute.
Following the summit, there was a strong commitment to continue to work towards
developing a sustainable and defined training pathway for clinical academics. The
need for a coordinated and integrated approach was highlighted. Some key
objectives were agreed upon for the next phase, including identifying and
engaging key advocates within government and leading institutions; publishing and
profiling the contributions of successful clinical academics to healthcare
outcomes; defining the stages of a clinical academic training pathway; and
establishing a mentoring programme for training clinical academics.
PMID- 28401724
TI - Advance Care Planning: is quality end of life care really that simple?
AB - The routine implementation of Advance Care Planning (ACP) is now a prominent
feature of policy directed at improving end of life care in Australia. However,
while complex ACP interventions may modestly reduce medical care at the end of
life and enable more people to die at home or outside of acute hospital settings,
existing legal, organisational, cultural and conceptual barriers limit the
implementation and utility of ACP. We suggest that meaningful improvements in end
of life care will not result from the institutionalisation of ACP but from more
significant changes to the design and delivery of care.
PMID- 28401725
TI - Advance Care Planning and Advance Care Directives: ideas whose time has passed?
PMID- 28401726
TI - The genomic potential of the Aspirin in Reducing Events in the Elderly and
Statins in Reducing Events in the Elderly studies.
AB - Human genetic studies are continuing to increase in size and scale, but the
availability of well-phenotyped longitudinal cohorts remains rare. Significant
infrastructure, investment and effort are required to establish and maintain high
quality cohorts with biobanking, genetic consent and repeated clinical data
measurements. Australia currently has two such cohorts established by Monash
University as part of community-based clinical trials in the elderly. Both
studies involve capture of demographic, mood, cognitive performance, physical
function, neuroimaging, audiometry and various clinical data types over an
average of 5 years. The ASPirin in Reducing Events in the Elderly (ASPREE) cohort
is comprised of 16 703 Australians aged over 70 years and 2411 Americans aged
over 65 years - recruited and randomised to either daily low-dose aspirin or
placebo to examine the preventative benefit of aspirin on a range of clinical
outcomes. The STAtins in Reducing Events in the Elderly (STAREE) study uses a
similar model, and is currently recruiting 10 000 men and women aged over 70
years across Australia randomised to either low-dose statins or placebo. Both
cohorts involve biobanking and consent for genetic research, with recruitment
through a network of general practitioners in the community. A combination of
whole-genome and targeted sequencing approaches will allow gene-phenotype
relationships to be explored within the context of detailed longitudinal data.
Genetic risk factors for late-onset high-burden conditions, such as
cardiovascular disease and dementia will be investigated, plus research into
other areas, such as healthy ageing and disease resilience will be possible due
to unique phenotypes of health.
PMID- 28401727
TI - Plug-assisted retrograde transvenous obliteration of splenorenal shunts for
refractory hepatic encephalopathy.
PMID- 28401728
TI - Developing a guideline for structured content and process in mental health
nursing handover.
AB - The process of handover has received recent attention within Australian health
care, as evidence linking patient safety with the quality of handover emerges.
Such links between clinical handover and patient safety have been reported
elsewhere in the literature, where it is posited that the safe care of patients
relies not only on the expertise and judgment of individual clinicians, teamwork,
and effective management, but hinges to a large extent on the quality of
information transferred from team to team. The present qualitative, descriptive
study used participant observations, focus groups, and interviews to investigate
the nursing handover in two acute mental health inpatient units in New South
Wales, Australia. Data collected as part of that investigation contributed to the
development of a handover guideline that incorporates the key components of
structure, content, and leadership. The research indicated a link between these
components, and further revealed the necessity to have other forums, such as
supervision and clinical review, to ensure that handover serves its intended
purpose in an efficient manner.
PMID- 28401729
TI - Correlation between experimental data of protonation of aromatic compounds at (+)
atmospheric pressure photoionization and theoretically calculated enthalpies.
AB - RATIONALE: The theoretical enthalpy calculated from the overall protonation
reaction (electron transfer plus hydrogen transfer) in positive-mode (+)
atmospheric-pressure photoionization (APPI) was compared with experimental
results for 49 aromatic compounds. A linear relationship was observed between the
calculated DeltaH and the relative abundance of the protonated peak. The
parameter gives reasonable predictions for all the aromatic hydrocarbon compounds
used in this study. METHODS: A parameter is devised by combining experimental MS
data and high-level theoretical calculations. A (+) APPI Q Exactive Orbitrap mass
spectrometer was used to obtain MS data for each solution. B3LYP exchange
correlation functions with the standard 6-311+G(df,2p) basis set was used to
perform density functional theory (DFT) calculations. RESULTS: All the molecules
with DeltaH <0 kcal/mol for the overall protonation reaction with toluene
clusters produced protonated ions, regardless of the desolvation temperature. For
molecules with DeltaH >0, molecular ions were more abundant at typical APPI
desolvation temperatures (300 degrees C), while the protonated ions became
comparable or dominant at higher temperatures (400 degrees C). The toluene
cluster size was an important factor when predicting the ionization behavior of
aromatic hydrocarbon ions in (+) APPI. CONCLUSIONS: The data used in this study
clearly show that the theoretically calculated reaction enthalpy (DeltaH) of
protonation with toluene dimers can be used to predict the protonation behavior
of aromatic compounds. When compounds have a negative DeltaH value, the types of
ions generated for aromatic compounds could be very well predicted based on the
DeltaH value. The DeltaH can explain overall protonation behavior of compounds
with DeltaH values >0. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28401732
TI - Responses of neonicotinoid resistant and susceptible Frankliniella fusca life
stages to multiple insecticide groups in cotton.
AB - BACKGROUND: Detection of neonicotinoid resistance in populations of tobacco
thrips, Frankliniella fusca Hinds, throughout the southeastern USA has motivated
an examination of alternative insecticides to control problematic infestations on
seedling cotton. The objective of this study was to refine understanding of stage
specific mortality and reduced oviposition of several common insecticides
(acephate, abamectin, cyantraniliprole, spinetoram, imidacloprid,
imidacloprid+thiodicarb, thiamethoxam) on neonicotinoid resistant and susceptible
F. fusca populations under laboratory and field conditions. RESULTS: Laboratory
studies revealed that the average number of eggs per female and larval or adult
survivorship responses differed by insecticide and were dependent on the
resistance status of the population. In the presence of neonicotinoids, the
resistant F. fusca populations exhibited lower mortality and higher egg counts
than the susceptible population. In the field study, similar patterns of
oviposition suppression were observed, indicating that some insecticides may
impact reproductive rate. CONCLUSION: This study shows that insecticides have
different effects on F. fusca oviposition events, larval and adult mortality that
are dependent on neonicotinoid resistance status. Because insecticides tested in
this study have varied activity on specific F. fusca life stages (e.g.
oviposition suppression, larvicidal activity, adulticidal activity), knowledge of
stage-specific activity can be used to improve control and enhance long-term
product stewardship. (c) 2017 Society of Chemical Industry.
PMID- 28401730
TI - DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their
decrease with age.
AB - Age-related bone loss in mice results from a decrease in bone formation and an
increase in cortical bone resorption. The former is accounted by a decrease in
the number of postmitotic osteoblasts which synthesize the bone matrix and is
thought to be the consequence of age-dependent changes in mesenchymal osteoblast
progenitors. However, there are no specific markers for these progenitors, and
conclusions rely on results from in vitro cultures of mixed cell populations.
Moreover, the culprits of such changes remain unknown. Here, we have used Osx1
Cre;TdRFP mice in which osteoprogenitors express the TdRFP fluorescent protein.
We report that the number of TdRFP-Osx1 cells, freshly isolated from the bone
marrow, declines by more than 50% between 6 and 24 months of age in both female
and male mice. Moreover, TdRFP-Osx1 cells from old mice exhibited markers of DNA
damage and senescence, such as gammaH2AX foci, G1 cell cycle arrest,
phosphorylation of p53, increased p21CIP1 levels, as well as increased levels of
GATA4 and activation of NF-kappaB - two major stimulators of the senescence
associated secretory phenotype (SASP). Bone marrow stromal cells from old mice
also exhibited elevated expression of SASP genes, including several pro
osteoclastogenic cytokines, and increased capacity to support osteoclast
formation. These changes were greatly attenuated by the senolytic drug ABT263.
Together, these findings suggest that the decline in bone mass with age is the
result of intrinsic defects in osteoprogenitor cells, leading to decreased
osteoblast numbers and increased support of osteoclast formation.
PMID- 28401733
TI - Effects of metals cadmium and chromium alone and in combination on the liver and
kidney tissue of male Spraque-Dawley rats: An ultrastructural and electron-energy
loss spectroscopy investigation.
AB - Heavy metal pollution has increased in the last decades. Water sources are
contaminated and human exposure is often long term exposure to variable amounts
of different metals. In this study, male Sprague-Dawley rats were exposed via
oral gavage for 28 days to cadmium (Cd) and chromium (Cr), alone and in
combination at concentrations 1000 times the human World Health Organization's
acceptable water limits. Rat equivalent dosages were used. Blood markers of liver
and kidney function were measured, changes to cellular morphology was determined
with transmission electron microscopy and the intracellular metal localisation
was determined with the electron energy-loss spectroscopy and energy filtered
transmission electron microscopy analysis. Both Cd and Cr caused changes to the
nuclear and mitochondrial membranes and irregular chromatin condensation of
hepatocytes. Cr exposure caused dilation of the rough endoplasmic reticulum
(rER). The combination caused nuclear and mitochondrial membrane damage as well
as irregular chromatin condensation. In the kidney tissue, Cd caused irregular
chromatin condensation in the cells of the proximal convoluted tubule (PCT). Cr
caused changes to the outer nuclear and mitochondrial membrane and chromatin
structure. The combination group caused membrane damage, irregular chromatin
condensation and rER changes in the PCT. All the metal groups showed damage to
the endothelial cells and pedicles, but not to the mesangial cells. Cd and Cr bio
accumulation was observed in the nucleus, mitochondria and rER of the liver and
kidney and therefore are responsible for the cellular observed damage that can
cause functional changes to the tissues and organs.
PMID- 28401731
TI - Impact of early personal-history characteristics on the Pace of Aging:
implications for clinical trials of therapies to slow aging and extend
healthspan.
AB - Therapies to extend healthspan are poised to move from laboratory animal models
to human clinical trials. Translation from mouse to human will entail challenges,
among them the multifactorial heterogeneity of human aging. To inform clinical
trials about this heterogeneity, we report how humans' pace of biological aging
relates to personal-history characteristics. Because geroprotective therapies
must be delivered by midlife to prevent age-related disease onset, we studied
young-adult members of the Dunedin Study 1972-73 birth cohort (n = 954). Cohort
members' Pace of Aging was measured as coordinated decline in the integrity of
multiple organ systems, by quantifying rate of decline across repeated
measurements of 18 biomarkers assayed when cohort members were ages 26, 32, and
38 years. The childhood personal-history characteristics studied were known
predictors of age-related disease and mortality, and were measured prospectively
during childhood. Personal-history characteristics of familial longevity,
childhood social class, adverse childhood experiences, and childhood health,
intelligence, and self-control all predicted differences in cohort members'
adulthood Pace of Aging. Accumulation of more personal-history risks predicted
faster Pace of Aging. Because trials of anti-aging therapies will need to
ascertain personal histories retrospectively, we replicated results using cohort
members' retrospective personal-history reports made in adulthood. Because many
trials recruit participants from clinical settings, we replicated results in the
cohort subset who had recent health system contact according to electronic
medical records. Quick, inexpensive measures of trial participants' early
personal histories can enable clinical trials to study who volunteers for trials,
who adheres to treatment, and who responds to anti-aging therapies.
PMID- 28401734
TI - Photoswitchable Sn-Cyt c Solid-State Devices.
AB - Electron transfer across proteins plays an important role in many biological
processes, including those relevant for the conversion of solar photons to
chemical energy. Previous studies demonstrated the generation of photocurrents
upon light irradiation in a number of photoactive proteins, such as photosystem I
or bacteriorhodopsin. Here, it is shown that Sn-cytochrome c layers act as
reversible and efficient photoelectrochemical switches upon integration into
large-area solid-state junctions. Photocurrents are observed both in the Soret
band (lambda = 405 nm) and in the Q band (lambda = 535 nm), with current on/off
ratios reaching values of up to 25. The underlying modulation in charge-transfer
rate is attributed to a hole-transport channel created by the photoexcitation of
the Sn-porphyrin.
PMID- 28401735
TI - Training of direct ophthalmoscopy using models.
AB - BACKGROUND: The time spent on ophthalmology training in medical schools has
reduced over the last decades, and the number of doctors unable to solve the most
basic ophthalmic problems has increased. METHODS: We conducted a questionnaire
with non-ophthalmologist doctors in order to assess the confidence level of their
direct ophthalmoscopy examination. This test is very important for the diagnosis
of diseases that could lead to blindness, and should be learned by all medical
students. RESULTS: The results showed that the doctors had difficulty and lacked
confidence in performing the examination. For this reason, we have developed a
new model and teaching method of direct ophthalmoscopy based on neuroscientific
concepts. The number of doctors unable to solve the most basic ophthalmic
problems has increased DISCUSSION: This model provides students with greater
involvement in the learning process as they build their own model, a practice
that shows the concepts of the physics behind direct ophthalmoscopy. IMPLICATION:
This will benefit the population by providing an early diagnosis of diseases that
threaten life and vision.
PMID- 28401736
TI - Microbiome yarns: microbiomology of winter rosy face,,.
PMID- 28401737
TI - Identifying frailty in primary care: A systematic review.
AB - AIM: Identification of frailty in the primary care setting could be improved with
the availability of easily identifiable markers of frailty. The purpose of this
article was to systematically review markers for frailty or risk tools that have
been validated in the ambulatory care setting. METHODS: Medline, PubMed, CIHAHL
and Embase databases were searched up to March 2016 for studies on frailty
markers in community-dwelling individuals 65 years or older. Studies were
included for review if they were carried out in primary care or outpatient
settings, used a validated definition of frailty, compared two or more markers,
and used randomized controlled trial, quasi-experimental or prospective cohort
designs. RESULTS: Of the 3405 titles screened, 12 were retained for review. All
of the studies were prospective cohort designs. Studies most frequently assessed
biological markers, such as immune, inflammation, endocrine biomarkers and
metabolic syndrome markers. Not one specific marker was repeatedly identified as
a definitive marker for frailty. CONCLUSIONS: There is a lack of psychometrically
sound and clinically useful frailty markers. There is a need for further research
to identify highly sensitive, specific and accurate markers that are feasible to
use in the context of busy primary care practice. Geriatr Gerontol Int 2017; 17:
1358-1377.
PMID- 28401738
TI - Clinical comparison of the efficacy of three different bowel preparation methods
on the infectious complications following transrectal ultrasonography-guided
prostate biopsy in nursing practice.
AB - AIMS AND OBJECTIVES: To assess the effects of three different bowel preparation
methods on the incidence of infectious complications in patients who underwent
transrectal ultrasonography-guided prostate biopsy. BACKGROUND: The standard
bowel preparation protocol for prostate biopsy has not been established. DESIGN:
A retrospective study in a single centre. METHODS: From January 2013-December
2015, the clinical records of 1,130 patients who underwent prostate biopsy were,
respectively, reviewed. All the patients received metronidazole prophylaxis
before biopsy. The patients were divided into three groups according to the bowel
preparation methods: patients in Group A (n = 402) received only soapy enema;
patients in Group B (n = 413) received polyethylene glycol; while patients in
Group C (n = 315) received polyethylene glycol plus povidone-iodine enema.
Infectious complications were classified as fever (>37.5 degrees C), urinary
tract infection and sepsis. The postoperative adverse events were also observed.
RESULTS: The overall postbiopsy infectious complications were observed in 48
(4.25%) patients of all the cases, including 23 (5.72%) cases in Group A, 20
(4.84%) cases in Group B and five patients (1.59%) in Group C. There was
significant difference among the groups (p = .018). In detail, these infectious
complications included 22 (1.95%) cases of fever and 26 (2.30%) cases of urinary
tract infection. No sepsis was observed among the total patients. The incidence
of adverse events was 14.43% (58/402) occurred in Group A, 25.91% (107/413) in
Group B and 26.67% (84/315) in Group C. The difference was statistically
significant. CONCLUSIONS: Our study confirmed that combined preparation regimens
of polyethylene glycol with povidone-iodine enema could significantly reduce the
postbiopsy infection rate. Conventional soapy enema is associated with less
adverse events. RELEVANCE TO CLINICAL PRACTICE: Findings of this study provide
useful evidence-based information for healthcare professionals. The application
of combined preparation regimens of polyethylene glycol with povidone-iodine
enema resulted in better improvement in the prevention of postbiopsy infection.
PMID- 28401739
TI - The Social Communication Questionnaire for adults with intellectual disability:
SCQ-AID.
AB - Autism spectrum disorder (ASD) frequently co-occurs with intellectual disability
(ID) and often remains undiagnosed until adulthood. The Social Communication
Questionnaire (SCQ) is a widely used measure to screen for ASD. To improve the
utility of the SCQ for adults with ID, the aim of this study was to develop an ID
specific and adult appropriate algorithm for the SCQ using a core set of valid
items. These items were identified in one sample (N = 226) and further cross
validated in a second, independent sample (N = 225) from Germany, England and the
U.S. The newly developed algorithm has 24 items compared with the 40 items in the
original instrument. The reduced item core set yielded similar diagnostic
validity as the original algorithm with good sensitivity values (0.81-0.89) and
low specificity values (0.62-0.72). Overall, these results suggest that the
removed items may not carry diagnostically relevant information in adults with
ID; thus, excluding these items may result in a more efficient and age
appropriate screening measure for this population. However, due to the low
specificity values, a comprehensive assessment is essential for a final
diagnostic assignment. Autism Res 2017, 10: 1481-1490. (c) 2017 International
Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28401740
TI - A novel HLA-B allele: HLA-B*40:242.
AB - The HLA-B*40:242 allele differs from B*40:54 by 1 nucleotide substitution at
position 190.
PMID- 28401741
TI - Oral alendronate in pediatric chronic recurrent multifocal osteomyelitis.
AB - Chronic recurrent multifocal osteomyelitis (CRMO) primarily affects children and
adolescents, and is characterized by episodic sterile osteomyelitis over several
years. No definitive treatment is available. Non-steroidal anti-inflammatory
drugs (NSAID) are common first-line agents, but provide limited improvement in
bone pain and do not affect disease duration. Several agents are utilized in the
case of non-response to NSAID, including corticosteroids, methotrexate, and tumor
necrosis factor-blocking agents. Bisphosphonates are increasingly being used.
Most case series involve cyclic i.v. pamidronate, but this restricts the social
lives of children and their families. Although oral medication has advantages
over cyclic i.v. infusion because it does not require repeated hospital
admissions, there have been no reports on treatment with oral bisphosphonates,
such as alendronate, in pediatric CRMO patients. This case report describes the
use of oral bisphosphonate as an alternative treatment in CRMO patients in whom
standard therapy has failed.
PMID- 28401742
TI - Encephalopathy and pancreatitis in a 3-year-old girl with Kawasaki disease.
PMID- 28401743
TI - Portosystemic shunt as a cause of congenital hyperinsulinemic hypoglycemia.
AB - Congenital hyperinsulinemic hypoglycemia (CHH) is characterized by the
inappropriate secretion of insulin from pancreatic beta cells in the presence of
hypoglycemia. We herein describe the case of a 5-month-old boy with CHH due to
congenital portosystemic shunt (CPSS). Insulin secreted from pancreatic beta
cells flows into the portal vein and is first metabolized in the liver. First
pass elimination of insulin in the liver leads to great decrease in insulin
concentration by approximately 40-80% in humans. CPSS accounts for a large
quantity of insulin delivery into the systemic circulation due to the lack of
hepatic first-pass elimination. Hypoglycemia can result from consistently high
levels of insulin after reaching normal glucose level. CPSS therefore should be
considered as a rare cause of CHH, especially in the case of post-prandial
hyperinsulinemic hypoglycemia.
PMID- 28401744
TI - FDG-PET in macrophage activation syndrome associated with systemic juvenile
idiopathic arthritis.
AB - We herein describe a case of systemic juvenile idiopathic arthritis (s-JIA)
associated macrophage activation syndrome (MAS) in which the 18F
fluorodeoxyglucose positron emission tomography (18F FDG-PET) findings were
characteristic. The pattern of greater 18F FDG accumulation into the spleen
compared with the liver was more remarkable in this patient compared with s-JIA.
This pattern, however, was also observed in cases of acute leukemia. In the
present patient, serum interleukin (IL)-18 was extremely elevated (255 000
pg/mL), whereas in leukemia patients it is mildly elevated (360-1480 pg/mL). 18F
FDG-PET might be a useful indicator of s-JIA and MAS in patients with fever of
unknown origin. The pattern of 18F FDG accumulation, however, can also be
observed in acute leukemia. The combination of 18F FDG-PET and serum IL-18 might
be useful for the diagnosis of s-JIA and MAS.
PMID- 28401745
TI - Hypocellular acute myeloid leukemia treated with bone marrow transplantation.
AB - Hypocellular acute myeloid leukemia (AML) mainly occurs in elderly patients, and
is extremely rare in childhood. There is still no established treatment for
hypocellular AML. We report the case of an 11-year-old boy with hypocellular AML
who was treated successfully with allogenic bone marrow transplantation (allo
BMT). He presented with fever, pallor and pancytopenia. Bone marrow aspiration
and biopsy confirmed a diagnosis of hypocellular AML. Although low-dose
cytarabine induced reduction of blasts, it did not lead to complete remission. He
subsequently received myeloablative conditioning and allo-BMT. Graft-versus-host
disease (GVHD) prophylaxis included short-course methotrexate and cyclosporine.
Neutrophil engraftment (>5 * 108 /L) and platelet recovery (>10 * 1010 /L) were
achieved on days 13 and 27, respectively. He developed acute GVHD of the skin
(grade 2), which responded well to treatment with prednisolone. He has remained
in complete remission for 5 years since allo-BMT. We consider allo-BMT to be
feasible for children with hypocellular AML.
PMID- 28401746
TI - Resolution of liver disease in transient abnormal myelopoiesis with fish oil
emulsion.
AB - Neonates with Down syndrome are at risk of developing transient abnormal
myelopoiesis (TAM), which is characterized by transient clonal myeloproliferation
of the blast cells. TAM can resolve spontaneously, but some patients die at an
early age due to organ failure. Liver fibrosis in TAM is a life-threatening
condition, but treatment options have not yet been established. Here, we report
on the case of an infant with TAM complicated by liver disease, whose
hyperbilirubinemia was successfully ameliorated with omega-3 fatty acid
(omega3FA) lipid emulsion. Timely omega3FA lipid emulsion may be a feasible
treatment for liver disease in TAM before serious liver damage develops.
PMID- 28401748
TI - The squid insurance plan: female Euprymna scolopes add potentially protective
bacteria to the egg coats of their clutches.
PMID- 28401747
TI - Dynamics of mono- and dual-species biofilm formation and interactions between
Staphylococcus aureus and Gram-negative bacteria.
AB - Microorganisms are not commonly found in the planktonic state but predominantly
form dual- and multispecies biofilms in almost all natural environments. Bacteria
in multispecies biofilms cooperate, compete or have neutral interactions
according to the involved species. Here, the development of mono- and dual
species biofilms formed by Staphylococcus aureus and other foodborne pathogens
such as Salmonella enterica subsp. enterica serovar Enteritidis, potentially
pathogenic Raoultella planticola and non-pathogenic Escherichia coli over the
course of 24, 48 and 72 h was studied. Biofilm formation was evaluated by the
crystal violet assay (CV), enumeration of colony-forming units (CFU cm-2 ) and
visualization using confocal laser scanning microscopy (CLSM) and scanning
electron microscopy (SEM). In general, Gram-negative bacterial species and S.
aureus interacted in a competitive manner. The tested Gram-negative bacteria grew
better in mixed dual-species biofilms than in their mono-species biofilms as
determined using the CV assay, CFU ml-2 enumeration, and CLSM and SEM
visualization. In contrast, the growth of S. aureus biofilms was reduced when
cultured in dual-species biofilms. CLSM images revealed grape-like clusters of S.
aureus and monolayers of Gram-negative bacteria in both mono- and dual-species
biofilms. S. aureus clusters in dual-species biofilms were significantly smaller
than clusters in S. aureus mono-species biofilms.
PMID- 28401749
TI - Amino-Acid-Induced Preferential Orientation of Perovskite Crystals for Enhancing
Interfacial Charge Transfer and Photovoltaic Performance.
AB - Interfacial engineering of perovskite solar cells (PSCs) is attracting intensive
attention owing to the charge transfer efficiency at an interface, which greatly
influences the photovoltaic performance. This study demonstrates the modification
of a TiO2 electron-transporting layer with various amino acids, which affects
charge transfer efficiency at the TiO2 /CH3 NH3 PbI3 interface in PSC, among
which the l-alanine-modified cell exhibits the best power conversion efficiency
with 30% enhancement. This study also shows that the (110) plane of perovskite
crystallites tends to align in the direction perpendicular to the amino-acid
modified TiO2 as observed in grazing-incidence wide-angle X-ray scattering of
thin CH3 NH3 PbI3 perovskite film. Electrochemical impedance spectroscopy reveals
less charge transfer resistance at the TiO2 /CH3 NH3 PbI3 interface after being
modified with amino acids, which is also supported by the lower intensity of
steady-state photoluminescence (PL) and the reduced PL lifetime of perovskite. In
addition, based on the PL measurement with excitation from different side of the
sample, amino-acid-modified samples show less surface trapping effect compared to
the sample without modification, which may also facilitate charge transfer
efficiency at the interface. The results suggest that appropriate orientation of
perovskite crystallites at the interface and trap-passivation are the niche for
better photovoltaic performance.
PMID- 28401751
TI - Down-Regulation of MicroRNA-210 Confers Sensitivity towards 1'S-1'
Acetoxychavicol Acetate (ACA) in Cervical Cancer Cells by Targeting SMAD4.
AB - MicroRNAs (miRNAs) are short non-coding RNAs that regulate genes
posttranscriptionally. Past studies have reported that miR-210 is up-regulated in
many cancers including cervical cancer, and plays a pleiotropic role in
carcinogenesis. However, its role in regulating response towards anti-cancer
agents has not been fully elucidated. We have previously reported that the
natural compound 1'S-1'-acetoxychavicol acetate (ACA) is able to induce
cytotoxicity in various cancer cells including cervical cancer cells. Hence, this
study aims to investigate the mechanistic role of miR-210 in regulating response
towards ACA in cervical cancer cells. In the present study, we found that ACA
down-regulated miR-210 expression in cervical cancer cells, and suppression of
miR-210 expression enhanced sensitivity towards ACA by inhibiting cell
proliferation and promoting apoptosis. Western blot analysis showed increased
expression of mothers against decapentaplegic homolog 4 (SMAD4), which was
predicted as a target of miR-210 by target prediction programs, following
treatment with ACA. Luciferase reporter assay confirmed that miR-210 binds to
sequences in 3'UTR of SMAD4. Furthermore, decreased in SMAD4 protein expression
was observed when miR-210 was overexpressed. Conversely, SMAD4 protein expression
increased when miR-210 expression was suppressed. Lastly, we demonstrated that
overexpression of SMAD4 augmented the anti-proliferative and apoptosis-inducing
effects of ACA. Taken together, our results demonstrated that down-regulation of
miR-210 conferred sensitivity towards ACA in cervical cancer cells by targeting
SMAD4. These findings suggest that combination of miRNAs and natural compounds
could provide new strategies in treating cervical cancer.
PMID- 28401752
TI - Water-Soluble Polythiophene for Two-Photon Excitation Fluorescence Imaging and
Photodynamic Therapy of Cancer.
AB - Positively charged water-soluble polythiophene (PT0) that could self-assemble
into nanoparticles in pure water solution was designed and synthesized. PT0
exhibited high photostabilities and pH stabilities, excellent biocompatibility,
strong 1O2 generation capability, and large two-photon absorption cross sections.
Moreover, we showed that the fluorescence of PT0 was unaffected by the
interference of biomolecules and metal ions. As an example application, PT0 was
demonstrated to be capable of simultaneous cell imaging and photodynamic therapy
under either one-photon or two-photon excitation modes.
PMID- 28401750
TI - The Ciliary Transition Zone: Finding the Pieces and Assembling the Gate.
AB - Eukaryotic cilia are organelles that project from the surface of cells to fulfill
motility and sensory functions. In vertebrates, the functions of both motile and
immotile cilia are critical for embryonic development and adult tissue
homeostasis. Importantly, a multitude of human diseases is caused by abnormal
cilia biogenesis and functions which rely on the compartmentalization of the
cilium and the maintenance of its protein composition. The transition zone (TZ)
is a specialized ciliary domain present at the base of the cilium and is part of
a gate that controls protein entry and exit from this organelle. The relevance of
the TZ is highlighted by the fact that several of its components are coded by
ciliopathy genes. Here we review recent developments in the study of TZ
proteomes, the mapping of individual components to the TZ structure and the
establishment of the TZ as a lipid gate.
PMID- 28401753
TI - Self-Assembly of Complex Multimetal Nanostructures from Perforated Lamellar Block
Copolymer Thin Films.
AB - We introduce a facile and effective fabrication of complex multimetallic
nanostructures through block copolymer self-assembly. Two- and three-dimensional
complex nanostructures, such as "nanomesh," "double-layered nanomeshes," and
"surface parallel cylinders on nanomesh," can be fabricated using the self
assembly of perforated lamellar morphology in block copolymer thin films.
Simultaneous integration of various metallic elements, including Pt, Au, and Co,
into the self-assembled morphologies generates multimetal complex nanostructures
with highly interconnected morphology and a large surface. The resultant metal
nanostructures with a large surface area, robust electrical connectivity, and
well-defined alloy composition demonstrate a high-performance electrochemical
catalysis for hydrogen evolution reaction (current density: 6.27 mA/cm2@0.1 V and
Tafel slope: 43 mV/dec).
PMID- 28401754
TI - Improving Sample Distribution Homogeneity in Three-Dimensional Microfluidic Paper
Based Analytical Devices by Rational Device Design.
AB - Paper-based devices are a portable, user-friendly, and affordable technology that
is one of the best analytical tools for inexpensive diagnostic devices. Three
dimensional microfluidic paper-based analytical devices (3D-MUPADs) are an
evolution of single layer devices and they permit effective sample dispersion,
individual layer treatment, and multiplex analytical assays. Here, we present the
rational design of a wax-printed 3D-MUPAD that enables more homogeneous
permeation of fluids along the cellulose matrix than other existing designs in
the literature. Moreover, we show the importance of the rational design of
channels on these devices using glucose oxidase, peroxidase, and 2,2'-azino-bis(3
ethylbenzothiazoline-6-sulfonic acid) (ABTS) reactions. We present an alternative
method for layer stacking using a magnetic apparatus, which facilitates fluidic
dispersion and improves the reproducibility of tests performed on 3D-MUPADs. We
also provide the optimized designs for printing, facilitating further studies
using 3D-MUPADs.
PMID- 28401755
TI - Structural Characterization of the Early Events in the Nucleation-Condensation
Mechanism in a Protein Folding Process.
AB - The nucleation-condensation mechanism represents a major paradigm to understand
the folding process of many small globular proteins. Although substantial
evidence has been acquired for this mechanism, it has remained very challenging
to characterize the initial events leading to the formation of a folding nucleus.
To achieve this goal, we used a combination of relaxation dispersion NMR
spectroscopy and molecular dynamics simulations to determine ensembles of
conformations corresponding to the denatured, transition, and native states in
the folding of the activation domain of human procarboxypeptidase A2 (ADA2h). We
found that the residues making up the folding nucleus tend to interact in the
denatured state in a transient manner and not simultaneously, thereby forming
incomplete and distorted versions of the folding nucleus. Only when all the
contacts between these key residues are eventually formed can the protein reach
the transition state and continue folding. Overall, our results elucidate the
mechanism of formation of the folding nucleus of a protein and provide insights
into how its folding rate can be modified during evolution by mutations that
modulate the strength of the interactions between the residues forming the
folding nucleus.
PMID- 28401756
TI - GPCR Activation and Endocytosis Induced by a 2D Material Agonist.
AB - Agonist-induced activation and endocytosis of G protein-coupled receptors (GPCRs)
are crucial for a number of physiological and pathological processes. However,
tools that are available for probing GPCR endocytosis have been insufficient.
Here, we developed a two-dimensional (2D) material agonist by supramolecular self
assembly between an endogenous agonist of kappa-opioid receptor (KOR) and 2D
molybdenum disulfide. The 2D material agonist has proven to be amenable for
eliciting GPCR activation and endocytosis in cells stably expressing KOR rather
than in those without KOR expression. Using super-resolution microscopy, we also
show that the 2D material agonist colocalizes well with GFP-fused KOR
intracellularly. Further, the endocytosed 2D material agonist can selectively
produce reactive oxygen species in cells that overly express KOR, as controlled
by light irradiation.
PMID- 28401757
TI - Porous SiO2 Hollow Spheres as a Solar Reflective Pigment for Coatings.
AB - This study starts with the synthesis of silica hollow spheres (HSs) by utilizing
in situ synthesized polystyrene (PS) microspheres as the template for the
deposition of a silica (SiO2) shell, followed by a slow gasification step in air
to remove the PS core. The size of HS and the thickness of the porous SiO2 shell
are tuned by varying the synthesis conditions of the PS latex and those of the
sol-gel deposition, respectively. Various HS powder samples are characterized by
ultraviolet-visible-near infrared (UV-vis-NIR) spectroscopy to determine their
diffuse reflectance. Furthermore, they are used as the filler in an acrylic
polymer matrix for the measurement of solar reflectivity on a solar spectrum
reflectometer. It turns out that both cavity size and the structure of the SiO2
shell are influential in the reflection of NIR and UV-vis light, respectively. In
addition, this study examines the effect on solar reflectivity of a selected
metal oxide with a SiO2 HS. In conclusion, the cavity size of the HS has a strong
impact on the reflectivity to NIR light whereas the shell itself affects the
reflection of UV-blue light.
PMID- 28401758
TI - Curcuminoid Demethylation as an Alternative Metabolism by Human Intestinal
Microbiota.
AB - Curcumin and other curcuminoids from Curcuma longa are important bioactive
compounds exhibiting various pharmacological activities. In addition to the known
reductive metabolism of curcuminoids, an alternative biotransformation of
curcuminoids by human gut microbiota is reported herein. A curcuminoid mixture,
composed of curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3),
was metabolized by the human intestinal bacterium Blautia sp. MRG-PMF1. 1 and 2
were converted to new metabolites by the methyl aryl ether cleavage reaction. Two
metabolites, demethylcurcumin (4) and bisdemethylcurcumin (5), were sequentially
produced from 1, and demethyldemethoxycurcumin (6) was produced from 2. Until
now, sequential reduction of the heptadienone backbone of curcuminoids was the
only known metabolism to occur in the human intestine. In this study, a new
intestinal metabolism of curcuminoids was discovered. Demethylation of
curcuminoids produced three new colonic metabolites that were already known as
promising synthetic curcumin analogues. The results could explain the observed
beneficial effects of turmeric.
PMID- 28401759
TI - Ultralight Cut-Paper-Based Self-Charging Power Unit for Self-Powered Portable
Electronic and Medical Systems.
AB - The development of lightweight, superportable, and sustainable power sources has
become an urgent need for most modern personal electronics. Here, we report a cut
paper-based self-charging power unit (PC-SCPU) that is capable of simultaneously
harvesting and storing energy from body movement by combining a paper-based
triboelectric nanogenerator (TENG) and a supercapacitor (SC), respectively.
Utilizing the paper as the substrate with an assembled cut-paper architecture, an
ultralight rhombic-shaped TENG is achieved with highly specific mass/volume
charge output (82 nC g-1/75 nC cm-3) compared with the traditional acrylic-based
TENG (5.7 nC g-1/5.8 nC cm-3), which can effectively charge the SC (~1 mF) to ~1
V in minutes. This wallet-contained PC-SCPU is then demonstrated as a sustainable
power source for driving wearable and portable electronic devices such as a
wireless remote control, electric watch, or temperature sensor. This study
presents a potential paper-based portable SCPU for practical and medical
applications.
PMID- 28401760
TI - Healable Cotton-Graphene Nanocomposite Conductor for Wearable Electronics.
AB - Electrically conductive materials based on cotton have important implications for
wearable electronics. We have developed flexible and conductive cotton fabrics
(~10 Omega/sq) by impregnation with graphene and thermoplastic polyurethane-based
dispersions. Nanocomposite fabrics display remarkable resilience against weight
pressed severe folding as well as laundry cycles. Folding induced microcracks can
be healed easily by hot-pressing, restoring initial electrical conductivity.
Impregnated cotton fabric conductors demonstrate better mechanical properties
compared to pure cotton and thermoplastic polyurethane maintaining breathability.
They also resist environmental aging such as solar irradiation and high humidity.
PMID- 28401761
TI - Solid Contact Ion-Selective Electrodes for in Situ Measurements at High Pressure.
AB - Solid contact polymeric ion-selective electrodes (SC-ISEs) have been fabricated
using microporous carbon (MUPC) as the ion-to-electron transducer, loaded with a
liquid membrane cocktail containing both ionophore and additive dissolved in
plasticizer. These SC-ISEs were characterized and shown to be suitable for
analysis in aqueous environments at pressures of 100 bar. Potassium ISEs,
prepared in this manner, showed excellent performance at both atmospheric and
elevated pressures, as evaluated by their response slopes and potential
stability. These novel SC-ISEs were shown to be capable of measuring K+ at
pressures under which traditional liquid-filled ISEs fail. Furthermore, the
effect of pressure on the response of these sensors had little or no effect on
potential, sensitivity, or limit of detection. High pressure sensor calibrations
were performed in standard solutions as well as simulated seawater samples to
demonstrate their usefulness as sensors in a deep-sea environment. These novel SC
ISE sensors show promise of providing the ability to make in situ real-time
measurements of ion-fluxes near deep-ocean geothermal vents.
PMID- 28401762
TI - Methane, Black Carbon, and Ethane Emissions from Natural Gas Flares in the Bakken
Shale, North Dakota.
AB - Incomplete combustion during flaring can lead to production of black carbon (BC)
and loss of methane and other pollutants to the atmosphere, impacting climate and
air quality. However, few studies have measured flare efficiency in a real-world
setting. We use airborne data of plume samples from 37 unique flares in the
Bakken region of North Dakota in May 2014 to calculate emission factors for BC,
methane, ethane, and combustion efficiency for methane and ethane. We find no
clear relationship between emission factors and aircraft-level wind speed or
between methane and BC emission factors. Observed median combustion efficiencies
for methane and ethane are close to expected values for typical flares according
to the US EPA (98%). However, we find that the efficiency distribution is skewed,
exhibiting log-normal behavior. This suggests incomplete combustion from flares
contributes almost 1/5 of the total field emissions of methane and ethane
measured in the Bakken shale, more than double the expected value if 98%
efficiency was representative. BC emission factors also have a skewed
distribution, but we find lower emission values than previous studies. The direct
observation for the first time of a heavy-tail emissions distribution from flares
suggests the need to consider skewed distributions when assessing flare impacts
globally.
PMID- 28401763
TI - Mineral Availability as a Key Regulator of Soil Carbon Storage.
AB - Mineral binding is a major mechanism for soil carbon (C) stabilization, and
mineral availability for C binding critically affects C storage. Yet, the
mechanisms regulating mineral availability are poorly understood. Here, we showed
that organic amendments in three long-term (23, 154, and 170 yrs, respectively)
field experiments significantly increased mineral availability, particularly of
short-range-ordered (SRO) phases. Two microcosm studies demonstrated that the
presence of roots significantly increased mineral availability and promoted the
formation of SRO phases. Mineral transformation experiments and isotopic labeling
experiments provided direct evidence that citric acid, a major component of root
exudates, promoted the formation of SRO minerals, and that SRO minerals acted as
"nuclei" for C retention. Together, these findings indicate that soil organic
amendments initialize a positive feedback loop by increasing mineral availability
and promoting the formation of SRO minerals for further C binding, thereby
possibly serving as a management tool for enhancing carbon storage in soils.
PMID- 28401764
TI - Stereoselectivity of Conformationally Restricted Glucosazide Donors.
AB - Glycosylations of 4,6-tethered glucosazide donors with a panel of model acceptors
revealed the effect of acceptor nucleophilicity on the stereoselectivity of these
donors. The differences in reactivity among the donors were evaluated in
competitive glycosylation reactions, and their relative reactivities were found
to be reflected in the stereoselectivity in glycosylations with a set of
fluorinated alcohols as well as carbohydrate acceptors. We found that the 2-azido
2-deoxy moiety is more beta-directing than its C-2-O-benzyl counterpart, as a
consequence of increased destabilization of anomeric charge development by the
electron-withdrawing azide. Additional disarming groups further decreased the
alpha-selectivity of the studied donors, whereas substitution of the 4,6
benzylidene acetal with a 4,6-di-tert-butyl silylidene led to a slight increase
in alpha-selectivity. The C-2-dinitropyridone group was also explored as an
alternative for the nonparticipating azide group, but this protecting group
significantly increased beta-selectivity. All studied donors exhibited the same
acceptor-dependent selectivity trend, and good alpha-selectivity could be
obtained with the weakest acceptors and most reactive donors.
PMID- 28401765
TI - Near-Infrared Fluorescent Proteins, Biosensors, and Optogenetic Tools Engineered
from Phytochromes.
AB - Phytochrome photoreceptors absorb far-red and near-infrared (NIR) light and
regulate light responses in plants, fungi, and bacteria. Their multidomain
structure and autocatalytic incorporation of linear tetrapyrrole chromophores
make phytochromes attractive molecular templates for the development of light
sensing probes. A subclass of bacterial phytochromes (BphPs) utilizes heme
derived biliverdin tetrapyrrole, which is ubiquitous in mammalian tissues, as a
chromophore. Because biliverdin possesses the largest electron-conjugated
chromophore system among linear tetrapyrroles, BphPs exhibit the most NIR-shifted
spectra that reside within the NIR tissue transparency window. Here we analyze
phytochrome structure and photochemistry to describe the molecular mechanisms by
which they function. We then present strategies to engineer BphP-based NIR
fluorescent proteins and review their properties and applications in modern
imaging technologies. We next summarize designs of reporters and biosensors and
describe their use in the detection of protein-protein interactions, proteolytic
activities, and posttranslational modifications. Finally, we provide an overview
of optogenetic tools developed from phytochromes and describe their use in light
controlled cell signaling, gene expression, and protein localization. Our review
provides guidelines for the selection of NIR probes and tools for noninvasive
imaging, sensing, and light-manipulation applications, specifically focusing on
probes developed for use in mammalian cells and in vivo.
PMID- 28401766
TI - Occurrence and In Vitro Bioactivity of Estrogen, Androgen, and Glucocorticoid
Compounds in a Nationwide Screen of United States Stream Waters.
AB - In vitro bioassays are sensitive, effect-based tools used to quantitatively
screen for chemicals with nuclear receptor activity in environmental samples. We
measured in vitro estrogen (ER), androgen (AR), and glucocorticoid receptor (GR)
activity, along with a broad suite of chemical analytes, in streamwater from 35
well-characterized sites (3 reference and 32 impacted) across 24 states and
Puerto Rico. ER agonism was the most frequently detected with nearly all sites
(34/35) displaying activity (range, 0.054-116 ng E2Eq L-1). There was a strong
linear relationship (r2 = 0.917) between in vitro ER activity and concentrations
of steroidal estrogens after correcting for the in vitro potency of each
compound. AR agonism was detected in 5/35 samples (range, 1.6-4.8 ng DHTEq L-1)
but concentrations of androgenic compounds were largely unable to account for the
in vitro activity. Similarly, GR agonism was detected in 9/35 samples (range, 6.0
43 ng DexEq L-1); however, none of the recognized GR-active compounds on the
target-chemical analyte list were detected. The utility of in vitro assays in
water quality monitoring was evident from both the quantitative agreement between
ER activity and estrogen concentrations, as well as the detection of AR and GR
activity for which there were limited or no corresponding target-chemical
detections to explain the bioactivity. Incorporation of in vitro bioassays as
complements to chemical analyses in standard water quality monitoring efforts
would allow for more complete assessment of the chemical mixtures present in many
surface waters.
PMID- 28401768
TI - Primary progressive multiple sclerosis presenting with severe predominant
cognitive impairment and psychiatric symptoms: A challenging case.
AB - Severe cognitive dysfunction is a frequent feature of multiple sclerosis (MS),
normally associated with later stages of the disease in adult population.
Nevertheless, progressive cognitive and neuropsychiatric disturbances might
rarely be the presenting and predominant symptom. In order to better characterize
this peculiar phenotype of MS, we report on the case of a 38-year-old man who
referred to our hospital with the suspect of hereditary leukodystrophy after 5
years of behavioral and mood abnormalities, global cognitive dysfunction,
clumsiness, and very mild pyramidal and cerebellar signs. Brain and spinal
magnetic resonance imaging (MRI) combined with cerebrospinal fluid (CSF) analysis
prompted the diagnosis of MS.
PMID- 28401767
TI - Expanded Target-Chemical Analysis Reveals Extensive Mixed-Organic-Contaminant
Exposure in U.S. Streams.
AB - Surface water from 38 streams nationwide was assessed using 14 target-organic
methods (719 compounds). Designed-bioactive anthropogenic contaminants (biocides,
pharmaceuticals) comprised 57% of 406 organics detected at least once. The 10
most-frequently detected anthropogenic-organics included eight pesticides
(desulfinylfipronil, AMPA, chlorpyrifos, dieldrin, metolachlor, atrazine, CIAT,
glyphosate) and two pharmaceuticals (caffeine, metformin) with detection
frequencies ranging 66-84% of all sites. Detected contaminant concentrations
varied from less than 1 ng L-1 to greater than 10 MUg L-1, with 77 and 278 having
median detected concentrations greater than 100 ng L-1 and 10 ng L-1,
respectively. Cumulative detections and concentrations ranged 4-161 compounds
(median 70) and 8.5-102 847 ng L-1, respectively, and correlated significantly
with wastewater discharge, watershed development, and toxic release inventory
metrics. Log10 concentrations of widely monitored HHCB, triclosan, and
carbamazepine explained 71-82% of the variability in the total number of
compounds detected (linear regression; p-values: < 0.001-0.012), providing a
statistical inference tool for unmonitored contaminants. Due to multiple modes of
action, high bioactivity, biorecalcitrance, and direct environment application
(pesticides), designed-bioactive organics (median 41 per site at MUg L-1
cumulative concentrations) in developed watersheds present aquatic health
concerns, given their acknowledged potential for sublethal effects to sensitive
species and lifecycle stages at low ng L-1.
PMID- 28401769
TI - The diagnostic dilemma of multiple sclerosis presenting with isolated cognitive
and behavioral disorders.
AB - Cognitive and behavioral symptoms are common in multiple sclerosis (MS), even
from the early stages of the disease, but they are considered to be rarely the
inaugural and predominant manifestation of the disease, thus jeopardizing early
and accurate diagnosis. This clinical commentary highlights a number of peculiar
characteristics that should be taken into consideration in case of primary
cognitive/neuropsychiatric dysfunction and white matter lesions of unclear
origin, in order to prompt appropriate diagnostic workup.
PMID- 28401770
TI - Myocardial infarction, periodontitis and depression.
PMID- 28401771
TI - Preoperative Magnetic Resonance Imaging in Patients With Stage I Invasive Ductal
Breast Cancer: A Prospective Randomized Study.
AB - BACKGROUND AND AIMS: Preoperative magnetic resonance imaging has become an
important complementary imaging technique in patients with breast cancer,
providing additional information for preoperative local staging. Magnetic
resonance imaging is recommended selectively in lobular breast cancer and in
patients with dense breast tissue in the case when mammography and ultrasound
fail to fully evaluate the lesion, but the routine use of magnetic resonance
imaging in all patients with invasive ductal carcinoma is controversial. The
purpose of this randomized study was to investigate the diagnostic value of
preoperative magnetic resonance imaging and its impact on short-term surgical
outcome in newly diagnosed unifocal stage I invasive ductal carcinoma. MATERIAL
AND METHODS: A total of 100 patients were randomized to either receive
preoperative breast magnetic resonance imaging or to be scheduled directly to
operation without magnetic resonance imaging on a 1:1 basis. There were 50
patients in both study arms. RESULTS: In 14 patients (28%), breast magnetic
resonance imaging detected an additional finding and seven of them were found to
be malignant. Six additional cancer foci were found in the ipsilateral breast and
one in the contralateral breast. Magnetic resonance imaging findings caused a
change in planned surgical management in 10 patients (20%). Mastectomy was
performed in six patients (12%) in the magnetic resonance imaging group and in
two patients (4%) in the control group ( p = 0.140). The breast reoperation rate
was 14% in the magnetic resonance imaging group and 24% in the control group ( p
= 0.202). The mean interval between referral and first surgical procedure was 34
days in the magnetic resonance imaging group and 21 days in the control group ( p
< 0.001). CONCLUSION: Preoperative magnetic resonance imaging may be beneficial
for some patients with early-stage invasive ductal carcinoma, but its routine use
is not recommended without specific indications.
PMID- 28401772
TI - Fear-based reasons for not engaging in sexual activity during pregnancy:
associations with sexual and relationship well-being.
AB - OBJECTIVE: Pregnant women consistently report fears that sexual activity could
harm their pregnancy. Little is known, however, about the degree to which women
report these fears as reasons for not having sex during pregnancy and whether
these fears relate to women's well-being. The aims of this study were to assess
the importance of women's fears of sexual activity harming the pregnancy in their
decision not to engage in sex during pregnancy, and the associations between
these fears and sexual and relationship well-being. METHODS: Pregnant women (N =
261) were recruited online to complete a survey that included a novel scale of
fear-based reasons for not engaging in sexual activity during pregnancy and
validated measures of sexual functioning, sexual satisfaction, sexual distress
and relationship satisfaction. RESULTS: Over half of the women (58.6%) reported
at least one fear as a reason for not engaging in sexual activity while pregnant,
though total fear scores were low. Greater fear-based reasons for not having sex
were associated with greater sexual distress but were unrelated to sexual
functioning, sexual satisfaction and relationship satisfaction. CONCLUSIONS:
Women who reported higher rates of refraining from sex due to fear that it could
harm their pregnancy reported greater sexual distress, but not lower sexual
functioning or sexual and relationship satisfaction. Results suggest that
interventions focused on minimizing fears of sexual activity during pregnancy may
not be essential for promoting women's broader sexual and relationship well-being
in pregnancy, but may help to reduce women's global feelings of worry and anxiety
about their sexual relationship.
PMID- 28401773
TI - Psychometric properties of the Ndetei-Othieno-Kathuku (NOK) Scale: A mental
health assessment tool for an African setting.
AB - BACKGROUND: Research suggests that psychiatric conditions in children and
adolescents are highly debilitating, with sparse resources for assessment and
treatment in low- and middle-income countries (LMICs). OBJECTIVES: The primary
aim of this study was to evaluate the reliability, validity, and latent factor
structure of an ethnographically-grounded assessment instrument for detecting
common mental health complaints among rural Kenyan children and adolescents.
METHODS: The Ndetei-Othieno-Kathuku Scale (NOK) was delivered to 2 282 children
aged 10 to 18 years old. Exploratory factor analysis identified four latent
factors. This structure was confirmed in subsequent confirmatory factor analyses.
External validity was explored by investigating associations among NOK factors
and Youth Self-Report DSM-oriented scales. RESULTS: Findings suggest the NOK
possesses good internal reliability and a four-factor latent structure
corresponding to depression, anxiety, somatic complaints, and a mixed factor.
Significant associations ranging from small to medium effect sizes were noted
between NOK factors and YSR DSM-oriented scales. CONCLUSIONS: Exploratory
findings suggest that the NOK possesses adequate psychometric properties among
this population. This ethnographically-grounded instrument may be uniquely suited
to screening for mental health complaints among Kenyan children and adolescents.
PMID- 28401774
TI - Effect of Descurainia sophia (L.) Webb ex Prantl on Adult Functional
Constipation: A Prospective Pilot Study.
AB - Chronic constipation is a common gastrointestinal disorder that effects an
estimated 12% to 30% of general population worldwide. Descurainia sophia L. known
commonly as flixweed acts as first-line medical treatment for constipation in
Iranian traditional medicine. The aim of this study was to assess the efficacy
and safety of this remedy for treating functional constipation by standard
assessments. The Rome III criteria for functional constipation were the basis for
diagnosis. All participants underwent a 4-week treatment. The primary end point
was the proportion of patients achieving >=3 complete spontaneous bowel movements
per week. Secondary outcome measures included Patient Assessment of Constipation
Symptom items, Bristol Stool Form Scale, numbers of laxatives/week used by
patients, and reported adverse effects. Thirty-five patients completed the
program with no important adverse effect. Fifty-four (4%) patients had >=3
complete spontaneous bowel movements per week. Descurainia sophia is safe and
effective in the treatment of chronic functional constipation.
PMID- 28401775
TI - Semi-automatic bowel wall thickness measurements on MR enterography in patients
with Crohn's disease.
AB - OBJECTIVE: To evaluate a semi-automatic method for delineation of the bowel wall
and measurement of the wall thickness in patients with Crohn's disease. METHODS:
53 patients with suspected or proven Crohn's disease were selected. Two
radiologists independently supervised the delineation of regions with active
Crohn's disease on MRI, yielding manual annotations (Ano1, Ano2). Three observers
manually measured the maximal bowel wall thickness of each annotated segment. An
active contour segmentation approach semi-automatically delineated the bowel
wall. For each active region, two segmentations (Seg1, Seg2) were obtained by
independent observers, in which the maximum wall thickness was automatically
determined. The overlap between (Seg1, Seg2) was compared with the overlap of
(Ano1, Ano2) using Wilcoxon's signed rank test. The corresponding variances were
compared using the Brown-Forsythe test. The variance of the semi-automatic
thickness measurements was compared with the overall variance of manual
measurements through an F-test. Furthermore, the intraclass correlation
coefficient (ICC) of semi-automatic thickness measurements was compared with the
ICC of manual measurements through a likelihood-ratio test. RESULTS: Patient
demographics: median age, 30 years; interquartile range, 25-38 years; 33 females.
The median overlap of the semi-automatic segmentations (Seg1 vs Seg2: 0.89) was
significantly larger than the median overlap of the manual annotations (Ano1 vs
Ano2: 0.72); p = 1.4 * 10-5. The variance in overlap of the semi-automatic
segmentations was significantly smaller than the variance in overlap of the
manual annotations (p = 1.1 * 10-9). The variance of the semi-automated
measurements (0.46 mm2) was significantly smaller than the variance of the manual
measurements (2.90 mm2, p = 1.1 * 10-7). The ICC of semi-automatic measurement
(0.88) was significantly higher than the ICC of manual measurement (0.45); p =
0.005. CONCLUSION: The semi-automatic technique facilitates reproducible
delineation of regions with active Crohn's disease. The semi-automatic thickness
measurement sustains significantly improved interobserver agreement. Advances in
knowledge: Automation of bowel wall thickness measurements strongly increases
reproducibility of these measurements, which are commonly used in MRI scoring
systems of Crohn's disease activity.
PMID- 28401776
TI - Molecular Characteristics of the Envelope of Vertically Transmitted HIV-1 Strains
from Infants with HIV Infection.
AB - Mother-to-child transmission (MTCT) of HIV offers a good opportunity to study the
dynamics of early viral evolution in the host environment to which the virus has
partially adapted. Such studies would throw light on the unique features of the
infecting viruses, which will subsequently help to design preventive or
therapeutic measures against the newly infecting and evolving strains of HIV.
Therefore, we undertook a study to determine the genetic divergence of proviral
envelope sequences from the HIV-infected infants (<2 years). Detailed analysis
revealed unique features of potential N-linked glycosylation sites (PNGS) and
their frequency of occurrence that built on the difference in length of the V1V2
region of the envelope sequences. Surprisingly, frequency of PNGS in the V5
region was found to revert rapidly, in about 75% of the sequences, which could
surmise a fitness disadvantage in the variant forms. Further, a stable net charge
was observed in the V2 and V3 regions prompting us to speculate on the
established interaction of the transmitted variant with the integrin alpha4beta7
receptor and R5 co-receptor, respectively. In brief, our observations suggest
that differences in the length of the variable regions and variation in the
frequency of PNGS in the envelope of the viruses obtained from very recently
infected individuals in our population could be important characteristics of the
unique quasispecies that is responsible for the spread of HIV in the early stages
of infection in MTCT.
PMID- 28401777
TI - ?
PMID- 28401778
TI - ?
PMID- 28401780
TI - ?
PMID- 28401779
TI - ?
PMID- 28401781
TI - ?
PMID- 28401782
TI - ?
PMID- 28401783
TI - ?
PMID- 28401784
TI - ?
PMID- 28401785
TI - ?
PMID- 28401786
TI - ?
PMID- 28401787
TI - ?
PMID- 28401789
TI - Psoriasis and Cardiovascular Disease: Two Sides of the Same Coin?
PMID- 28401788
TI - Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative
metabolism in sensorimotor regions after stroke.
AB - Individuals with type-2 diabetes mellitus experience poor motor outcomes after
ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts
neuronal integrity and function, yet little work has considered how these
neuronal changes affect sensorimotor outcomes after stroke. Here, we considered
how type-2 diabetes impacted the structural and metabolic function of the
sensorimotor cortex after stroke using volumetric magnetic resonance imaging
(MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the
combination of chronic stroke and type-2 diabetes would negatively impact the
integrity of sensorimotor cortex as compared to individuals with chronic stroke
alone. Compared to stroke alone, individuals with stroke and diabetes had lower
cortical thickness bilaterally in the primary somatosensory cortex, and primary
and secondary motor cortices. Individuals with stroke and diabetes also showed
reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional
primary and secondary motor cortex thicknesses were negatively related to
sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group
such that those with thinner primary and secondary motor cortices had better
motor function. These data suggest that type-2 diabetes alters cerebral energy
metabolism, and is associated with thinning of sensorimotor cortex after stroke.
These factors may influence motor outcomes after stroke.
PMID- 28401791
TI - To Screen, or Not to Screen, That is the Question.
PMID- 28401790
TI - Comparison of Iodixanol and Iopromide in Patients With Renal Insufficiency and
Congestive Heart Failure Undergoing Coronary Angiography by Hemodynamic
Monitoring.
AB - We investigated the impact of contrast media (CM) with different osmolality on
cardiac preload in patients with chronic kidney disease (CKD) and congestive
heart failure (CHF). Patients with CKD and CHF were equally randomized to receive
either iso-osmolar contrast media (IOCM) iodixanol or low-osmolar contrast media
iopromide. We measured cardiac preload indexes by invasive hemodynamic monitoring
before and after CM injection. Major adverse cardiac events postprocedures were
recorded. Increase in extravascular lung water index was only seen in the
iopromide group ( P < .001), while global end diastolic index and central venous
pressure were all significantly increased from baseline in the both groups ( P <
.001, respectively), and the increase in cardiac preload indexes was
significantly greater in the iopromide group than in the iodixanol group ( P <
0.001). The overall incidence of acute heart failure was more frequently observed
in the iopromide group ( P = 0.027). Low-osmolar contrast media iopromide
significantly increased cardiac preload in patients with CKD and CHF undergoing
cardiac catheterization procedures compared with IOCM iodixanol.
PMID- 28401792
TI - Assessment of Long-Term Mate Preferences in Iran.
AB - Previous research suggests that assessment of mate preferences has received
relatively little psychometric attention from researchers, particularly in non
Western cultures. The current research was designed to (1) extend previous
findings on long-term mate preferences by using a qualitative strategy, (2)
develop a psychometrically sound scale for assessment of long-term mate
preferences in men, and (3) develop a sex-neutral scale for assessment of long
term mate preferences. Six dimensions of mate preferences emerged for men: F =
family/domesticity, A = attractiveness/sexuality, K = kindness/dependability, E =
education/intelligence, R = religiosity/chastity, and S = status/resources. These
male-specific dimensions of mate preferences showed satisfactory concurrent and
convergent validity as well as high internal consistency coefficients. We mixed
the female- and male-specific measures of mate preferences and arrived at 20
characteristics without culture- or sex-specific content. We further hypothesized
that the 20-item scale of mate preferences would have a five-factor structure
(i.e., kindness/dependability, attractiveness/sexuality, status/resources,
education/intelligence, religiosity/chastity [KASER]) in men and women and that
this model would replicate sex differences cited in the evolutionary
psychological literature. Measurement invariance was evidenced across sexes and
sex differences accorded with those in the literature. Therefore, the five-factor
model of long-term mate preferences (i.e., KASER model) as measured by the
Iranian Mate Preferences Scale-20 may be used to evaluate long-term mate
preferences in men and women in Iran. Limitations are noted and future directions
are discussed in the light of evolutionary perspective on human mating
psychology.
PMID- 28401793
TI - Developing a Customized Perfusion Bioreactor Prototype with Controlled Positional
Variability in Oxygen Partial Pressure for Bone and Cartilage Tissue Engineering.
AB - Skeletal development is a multistep process that involves the complex interplay
of multiple cell types at different stages of development. Besides biochemical
and physical cues, oxygen tension also plays a pivotal role in influencing cell
fate during skeletal development. At physiological conditions, bone cells
generally reside in a relatively oxygenated environment whereas chondrocytes
reside in a hypoxic environment. However, it is technically challenging to
achieve such defined, yet diverse oxygen distribution on traditional in vitro
cultivation platforms. Instead, engineered osteochondral constructs are commonly
cultivated in a homogeneous, stable environment. In this study, we describe a
customized perfusion bioreactor having stable positional variability in oxygen
tension at defined regions. Further, engineered collagen constructs were coaxed
into adopting the shape and dimensions of defined cultivation platforms that were
precasted in 1.5% agarose bedding. After cultivating murine embryonic stem cells
that were embedded in collagen constructs for 50 days, mineralized constructs of
specific dimensions and a stable structural integrity were achieved. The end
products, specifically constructs cultivated without chondroitin sulfate A (CSA),
showed a significant increase in mechanical stiffness compared with their initial
gel-like constructs. More importantly, the localization of osteochondral cell
types was specific and corresponded to the oxygen tension gradient generated in
the bioreactor. In addition, CSA in complementary with low oxygen tension was
also found to be a potent inducer of chondrogenesis in this system. In summary,
we have demonstrated a customized perfusion bioreactor prototype that is capable
of generating a more dynamic, yet specific cultivation environment that could
support propagation of multiple osteochondral lineages within a single engineered
construct in vitro. Our system opens up new possibilities for in vitro research
on human skeletal development.
PMID- 28401795
TI - Corrigendum.
PMID- 28401794
TI - Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of
Thyroid Remnant.
AB - BACKGROUND: Chinese data on the efficacy of low- and high-dose radioiodine for
thyroid remnant are still absent. The aim of the study was to investigate whether
a low dose of radioiodine is as effective as a high dose for remnant ablation in
Chinese patients. METHODS: Patients presenting for radioiodine ablation in the
authors' department were included. Inclusion criteria were aged >=16 years, total
or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N
stage, and M0. All patients were randomly allocated to either the high-dose group
of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response
to treatment was defined as successful or unsuccessful after a six- to nine-month
interval. Ablation was considered to be successful if patients fulfilled the
following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body
scanning and a negative level of serum thyroglobulin. RESULTS: There were 327
patients enrolled between January 2013 and December 2014. More than 95% had
papillary thyroid cancer. Data could be analyzed for 278 cases (Mage = 44 years;
71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate
of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose
group, and 86.2% in the high-dose group. There was no difference between the two
groups (p = 0.509). CONCLUSIONS: In Chinese patients with differentiated thyroid
carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a
high dose of 3700 MBq for thyroid remnant ablation.
PMID- 28401796
TI - Unicompartmental Knee Arthroplasties are Performed on the Patients with
Radiologically Too Mild Osteoarthritis.
AB - BACKGROUND: Patient selection for either total knee arthroplasty or
unicompartmental knee arthroplasty remains controversial. The latter has several
reported advantages over total knee arthroplasty, but it also appears to have
significant drawbacks in terms of revision rates. AIMS: This study aimed to
determine the influence of the preoperative degree of osteoarthritis on the risk
of reoperation following unicompartmental knee arthroplasty. METHODS: Surgery was
carried out on 294 knees in 241 patients between 2001 and 2012 at a single
institute, using cemented Oxford phase III unicompartmental knee arthroplasty.
The mean age at the time of operation was 67 years, and the mean follow-up time
was 8.7 years. RESULTS AND CONCLUSION: The knees with a preoperative Kellgren
Lawrence grade of 0-2 osteoarthritis had a higher risk of reoperation than those
with a Kellgren-Lawrence grade of 3-4 (odds ratio = 1.89; 95% confidence
interval, 1.03-3.45; p = 0.04). In addition, the knees with a medial joint space
width of more than 1 mm or a high medial/lateral joint space width ratio had an
increased risk of reoperation. In conclusion, we suggest that unicompartmental
knee arthroplasty should only be performed in cases showing severe osteoarthritis
in preoperative radiographs, with medial bone-on-bone contact, and a
medial/lateral ratio of <20%.
PMID- 28401797
TI - The State of Skewed X Chromosome Inactivation is Retained in the Induced
Pluripotent Stem Cells from a Female with Hemophilia B.
AB - Skewed X chromosome inactivation (XCI) is a rare reason for hemophilia B in
females. It is indefinite whether X chromosome reactivation (XCR) would occur
when cells of hemophilia B patients with skewed XCI were reprogrammed into
induced pluripotent stem cells (iPSCs). In this study, we investigated a female
hemophilia B patient with a known F9 gene mutation: c.676C>T, p.Arg226Trp. We
demonstrated that skewed XCI was the pathogenesis of the patient, and we
successfully generated numerous iPSC colonies of the patient from peripheral
blood mononuclear cells (PBMNCs), which was the first time for generating
hemophilia-specific iPSCs from PBMNCs. Then we detected the XCI state of these
iPSCs. Ninety-two iPSC lines were picked for XCI analysis. All of them retained
an inactive X chromosome, which could be proved by amplification of the androgen
receptor gene and XIST (X inactivation-specific transcript), expression of
H3K27me3, and existence of XIST clouds in XIST RNA fluorescence in situ
hybridization (FISH) analysis. We attempted to obtain iPSC lines with the wild
type F9 gene on the active X chromosome for further disease treatment. But it
turned out that the patient's iPSCs were still skewed such as the somatic cells
with 92 iPSC lines having mutant F9 on the active X chromosome. In conclusion,
skewed XCI is one reason for hemophilia in females. PBMNCs are excellent somatic
cell resources for hemophilia patients to do reprogramming. More attentions
should be paid to generate naive iPSCs with two active X chromosomes for further
clinical disease treatment. The state of skewed XCI is retained in the iPSCs from
a female with hemophilia B.
PMID- 28401800
TI - A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic
Nutritional Index.
AB - The prognostic impact of nutritional status in patients with pulmonary embolism
(PE) is poorly understood. A well-accepted nutritional status parameter,
prognostic nutritional index (PNI), which was first demonstrated to be valuable
in patients with cancer and gastrointestinal surgery, was introduced to patients
with PE. Our aim was to evaluate the predictive value of PNI in outcomes of
patients with PE. We evaluated the in-hospital and long-term (53.8 +/- 5.4
months) prognostic impact of PNI on 251 patients with PE. During a median follow
up of 53.8 +/- 5.4 months, 27 (11.6%) patients died in hospital course and 31
(13.4%) died in out-of-hospital course. The patients with lower PNI had
significantly higher in-hospital and long-term mortality. The Cox proportional
hazard analyses showed that PNI was associated with an increased risk of all
cause death for both unadjusted model and adjusted for all covariates. Our study
demonstrated that PNI, calculated based on serum albumin level and lymphocyte
count, is an independent prognostic factor for mortality in patients with PE.
PMID- 28401798
TI - Most Frequently Reported Prescription Medications and Supplements in Couples
Planning Pregnancy: The LIFE Study.
AB - OBJECTIVE: To identify frequently reported prescription medications and
supplements among couples planning pregnancy because there is a lack of
descriptive information on these agents in women and men who are trying to
conceive. METHODS: Five hundred one couples enrolled in the Longitudinal Study of
Infertility and the Environment, which took place between 2005 and 2009.
Participants reported prescription medications as well as prescription and over
the-counter supplements used through interviews at study enrollment and through
daily dairies during the 12-month follow-up. We identified prescription
medications and supplements prospectively reported by >=1% of women and men at
baseline and from daily journal information grouped into 3-month preconception
follow-up intervals while couples tried for pregnancy. RESULTS: The 5 most
reported prescription medications among women were levothyroxine (5.8%),
cetirizine (2.6%), fluticasone (2.4%), escitalopram (1.8%), and fluoxetine (1.8%)
and for men were lisinopril (2.0%), mometasone (2.0%), fexofenadine (1.8%),
atorvastatin (1.6%), and montelukast (1.6%). The most reported supplements were
multivitamins (63.3%, 43.5%) and fish oil (13.2%, 9.4%) for women and men,
respectively, and prenatal vitamins (22.0%) for women. For women during the first
3 months of follow-up, prenatal vitamins (6.0%) and antibiotics (1.2%-2.6%) were
among the most frequently started medications. During the next 3 months,
clomiphene (4.5%) was the most frequently initiated medication. CONCLUSIONS:
Couples trying for pregnancy reported a variety of prescription medications and
supplements, and they differed by gender. Preconception guidance should address
medication and supplement use to avoid potential exposures associated with
adverse reproductive and perinatal outcomes.
PMID- 28401801
TI - Thrombophilia in 153 Patients With Premature Cardiovascular Disease <=Age 45.
AB - We assessed contributions of thrombophilia to premature cardiovascular disease
(CVD) events (<= age 45) in 153 patients. Test results of thrombophilia
hypofibrinolysis were obtained in 153 patients with CVD <= age 45, 110 healthy
normal controls, and 110 patients who had venous thromboembolism (VTE) without
CVD. Of the 153 patients with CVD, 121 (79%) had sustained myocardial infarction,
70 (46%) had coronary artery stenting, and 53 (35%) had coronary artery bypass
grafts. The first CVD events occurred at ages >20 to 35 in 47 patients and at
ages >35 to 45 in 106 patients. At study entry, median low-density lipoprotein
cholesterol was 126 mg/dL, 56 (37%) smoked, 56 (37%) had hypertension, and 56
(37%) were diabetic. Cases differed from normal controls for high factor VIII (10
[22%] of 45 vs 7 of 103 [7%], P = .007), high homocysteine (32 [21%] of 151 vs 5
[5%] of 107, P = .0002), low free protein S (5 [11%] of 44 vs 2 [2%] of 96, P =
.032), high anticardiolipin antibodies (ACLA) IgM (11 [9%] of 129 vs 2 [2%] of
109, P = .024), high lipoprotein (a) [Lp(a)] (46 [30%] of 151 vs 21 [19%] of 110,
P = .038), and the lupus anticoagulant (4 [11%] of 37 vs 2 [2%] of 110, P =
.035). There were no differences ( P > .05) between cases and VTE controls except
free protein S and Lp(a). Free protein S was more often low in VTE controls (24
[28%] of 85 vs 5 [11%] of 44, P = .03) and Lp(a) was more often high in cases (46
[30%] of 151, VTE controls 12 [17%] of 71, P = .032). In 153 patients with
premature CVD <= age 45, thrombophilia was pervasive (high factor VIII,
homocysteine, ACLA IgM, low free protein S, high Lp(a), and lupus anticoagulant),
evidencing thrombotic contribution to premature CVD. Moreover, thrombophilia in
patients with premature CVD was comparable to VTE controls, emphasizing the
pervasive nature of thrombophilia in premature CVD.
PMID- 28401802
TI - The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.
AB - Differences in warfarin maintenance dosages based on the presence of
polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through
dosage adjustment according to routine guidelines. Little is known about whether
routine therapy could provide consensus anticoagulation control for patients with
different genotypes. This study was carried out to compare anticoagulant control
in patients with different genotypes. Six hundred seventy patients using warfarin
according to Chinese guidelines were enrolled. Warfarin dosages and monitored
international normalized ratios (INRs) were recorded. Genotypes of VKORC1
rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms
were determined. Warfarin dosages and INR were compared between genotypes.
Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the
AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR
range. The INR values of patients with AACC*F*F*1*3 were unstable and did not
enter the stable state control phase until after 35 days. The peak INR of
patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some
values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1
or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with
the AACC*F*F*1*1 polymorphism. This study found that routine medication with
warfarin provides significantly different levels of anticoagulant control between
patients with wild-type genotypes and patients with heterozygous polymorphism
genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous
polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with
warfarin to increase efficacy and safety in anticoagulant treatment.
PMID- 28401803
TI - Imaging Advances in Urolithiasis.
AB - The prevalence of urinary stones in the United States has been described as 1 in
11 persons reporting a history of stones. Imaging plays a crucial role in
diagnosis, management, and follow-up for these patients and imaging technology
over the last 100 years has advanced as the disease prevalence has increased. CT
remains the gold standard for imaging urolithiasis and changes in this
technology, with the addition of multidetector CT and dual-energy CT, as well as
the changes in utilization of CT, have decreased the radiation dose encountered
by patients and allowed for improved stone detection. The use of digital
tomography has been introduced for follow-up of recurrent stone formers offering
the potential to lower radiation exposure over the course of a patient's lifelong
treatment. However, there is still a demand for improved imaging techniques to
detect smaller stones and stones in larger patients at lower radiation doses as
well as the continued need for the judicious use of all imaging modalities for
healthcare cost containment and patient safety.
PMID- 28401804
TI - Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial
Clearance in Neonatal Sepsis in Rats.
AB - Sepsis is the main cause of morbidity and mortality in neonates. Mesenchymal
stromal cells (MSCs) are potent immune-modulatory cells. Their effect in neonatal
sepsis has never been explored. We hypothesized that human umbilical cord-derived
MSCs (hUC-MSCs) improve survival in experimental neonatal sepsis. Sepsis was
induced in 3-day-old rats by intravenous injection of Escherichia coli (5 *
105/rat). One hour after infection, rats were treated intravenously with normal
saline, hUC-MSCs, or with interferon-gamma preconditioned hUC-MSCs (107
cells/kg). Eighteen hours after infection, survival, bacterial counts, lung
neutrophil and macrophage influx, phagocytosis and apoptosis of splenocytes
plasma, and LL-37 concentration were evaluated. Animals were observed for
survival for 72 h after E. coli injection. Treatment with either hUC-MSCs or
preconditioned hUC-MSCs significantly increased survival (hUC-MSCs, 81%;
preconditioned hUC-MSCs, 89%; saline, 51%; P < 0.05). Both hUC-MSCs and
preconditioned hUC-MSCs enhanced bacterial clearance. Lung neutrophil influx was
decreased with preconditioned hUC-MSCs. The number of activated macrophages
(CD206+) in the spleen was increased with hUC-MSCs and preconditioned hUC-MSCs;
preconditioned hUC-MSCs increased the phagocytic activity of CD206+ macrophages.
hUC-MSCs and preconditioned hUC-MSCs decreased splenocyte apoptosis in E. coli
infected rats. Finally, LL-37 plasma levels were elevated in neonatal rats
treated with hUC-MSCs or preconditioned hUC-MSCs. hUC-MSCs enhance survival and
bacterial clearance in experimental neonatal sepsis. hUC-MSCs may be an effective
adjunct therapy to reduce neonatal sepsis-related morbidity and mortality.
PMID- 28401805
TI - * An Engineered Multiphase Three-Dimensional Microenvironment to Ensure the
Controlled Delivery of Cyclic Strain and Human Growth Differentiation Factor 5
for the Tenogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells.
AB - At present, injuries or rupture of tendons are treated by surgical repair or
conservative approaches with unpredictable clinical outcome. Alternative
strategies to repair tendon defects without the undesirable side effects
associated with the current options are needed. With this in mind, a tissue
engineering approach has gained considerable attention as a promising strategy.
Here we investigated a synthetic three-dimensional (3D) microenvironment able to
interact with stem cells and inducing, via coupled biochemical and physical
signals, their early commitment toward the tenogenic lineage. This multiphase 3D
construct consisted of a braided hyaluronate elastic band merged with human bone
marrow mesenchymal stem cells (hBMSCs) and poly-lactic-co-glycolic acid
microcarriers loaded with human growth differentiation factor 5 (hGDF-5) by means
of fibrin hydrogel. The multiphase structure allowed hBMSC culture under cyclic
strain within a microenvironment where a controlled amount of hGDF-5 was
regularly delivered. The cooperative biochemical and physical stimuli induced
significantly increased expression of tenogenic markers, such as collagen type I
and III, decorin, scleraxis, and tenascin-C, within only 3 days of dynamic hBMSC
culture. This approach opens exciting perspectives for future development of
engineered tendon tissue substitutes.
PMID- 28401806
TI - Quantification of mycotoxins in vegetable oil by UPLC-MS/MS after magnetic solid
phase extraction.
AB - The detection of mycotoxin contamination in foodstuffs is highly significant for
public health. Herein we report an analytical method based on magnetic solid
phase extraction (MSPE) and UPLC-MS/MS for the simultaneous determination of
mycotoxins, including fumonisins B1 (FB1), zearalenone (ZON) and ochratoxin A
(OTA), in vegetable oil. Magnetic nanoparticles coated with double layers of
silicon dioxide were synthesised and found to be an effective MSPE adsorbent for
mycotoxins. The proposed MSPE procedure serves not only for sample clean-up but
also for mycotoxin enrichment that enhances greatly the assay's sensitivity.
Under the selected MSPE conditions, linear matrix-matched calibration curves were
obtained for mycotoxins in a concentration range from 0.178 to 625 MUg kg-1. The
limits of detection were 0.210 MUg kg-1 for FB1, 0.0800 MUg kg-1 for OTA and 1.03
MUg kg-1 for ZON. The proposed MSPE UPLC-MS/MS method was applied for the
determination of mycotoxins in vegetable oil samples, including maize oil,
rapeseed oil and soybean oil. ZON was detected in a maize oil at 101 MUg kg-1,
which is below the European Union limit of 200 MUg kg-1 in foodstuffs.
PMID- 28401809
TI - Internal Rotation of the Proximal Fibular Fragment Producing Symptomatic
Tibiofibular Impingement after an SER-II Ankle Fracture: A Case Report.
PMID- 28401807
TI - Biophysical Stimulation for Engineering Functional Skeletal Muscle.
AB - Tissue engineering is a promising therapeutic strategy to regenerate skeletal
muscle. However, ex vivo cultivation methods typically result in a low
differentiation efficiency of stem cells as well as grafts that resemble the
native tissues morphologically, but lack contractile function. The application of
biomimetic tensile strain provides a potent stimulus for enhancing myogenic
differentiation and engineering functional skeletal muscle grafts. We reviewed
integrin-dependent mechanisms that potentially link mechanotransduction pathways
to the upregulation of myogenic genes. Yet, gaps in our understanding make it
challenging to use these pathways to theoretically determine optimal ex vivo
strain regimens. A multitude of strain protocols have been applied to in vitro
cultures for the cultivation of myogenic progenitors (adipose- and bone marrow
derived stem cells and satellite cells) and transformed murine myoblasts, C2C12s.
Strain regimens are characterized by orientation, amplitude, and time-dependent
factors (effective frequency, duration, and the rest period between successive
strain cycles). Analysis of published data has identified possible
minimum/maximum values for these parameters and suggests that uniaxial strains
may be more potent than biaxial strains, possibly because they more closely mimic
physiologic strain profiles. The application of these biophysical stimuli for
engineering 3D skeletal muscle grafts is nontrivial and typically requires custom
designed bioreactors used in combination with biomaterial scaffolds.
Consideration of the physical properties of these scaffolds is critical for
effective transmission of the applied strains to encapsulated cells. Taken
together, these studies demonstrate that biomimetic tensile strain generally
results in improved myogenic outcomes in myogenic progenitors and differentiated
myoblasts. However, for 3D systems, the optimization of the strain regimen may
require the entire system including cells, biomaterials, and bioreactor, to be
considered in tandem.
PMID- 28401808
TI - Associations between volume changes and spatial dose metrics for the urinary
bladder during local versus pelvic irradiation for prostate cancer.
AB - BACKGROUND: Inter-fractional variation in urinary bladder volumes during the
course of radiotherapy (RT) for prostate cancer causes deviations between planned
and delivered doses. This study compared planned versus daily cone-beam CT (CBCT)
based spatial bladder dose distributions, for prostate cancer patients receiving
local prostate treatment (local treatment) versus prostate including pelvic lymph
node irradiation (pelvic treatment). MATERIAL AND METHODS: Twenty-seven patients
(N = 15 local treatment; N = 12 pelvic treatment) were treated using daily image
guided RT (1.8 Gy@43-45 fx), adhering to a full bladder/empty rectum protocol.
For each patient, 9-10 CBCTs were registered to the planning CT, using the
clinically applied translations. The urinary bladder was manually segmented on
each CBCT, 3 mm inner shells were generated, and semi and quadrant sectors were
created using axial/coronal cuts. Planned and delivered DVH metrics were compared
across patients and between the two groups of treatment (t-test, p < .05; Holm
Bonferroni correction). Associations between bladder volume variations and the
dose-volume histograms (DVH) of the bladder and its sectors were evaluated
(Spearman's rank correlation coefficient, rs). RESULTS: Bladder volumes varied
considerably during RT (coefficient of variation: 16-58%). The population
averaged planned and delivered DVH metrics were not significantly different at
any dose level. Larger treatment bladder volumes resulted in increased absolute
volume of the posterior/inferior bladder sector receiving intermediate-high
doses, in both groups. The superior bladder sector received less dose with larger
bladder volumes for local treatments (rs +/- SD: -0.47 +/- 0.32), but larger
doses for pelvic treatments (rs +/- SD: 0.74 +/- 0.24). CONCLUSIONS: Substantial
bladder volume changes during the treatment course occurred even though patients
were treated under a full bladder/daily image-guided protocol. Larger bladder
volumes resulted in less bladder wall spared at the posterior-inferior sector,
regardless the treatment received. Contrary, larger bladder volumes meant larger
delivered doses to the superior bladder sector for pelvic RT but smaller doses
for local treatments.
PMID- 28401811
TI - Hooked on a feeling? Exploring desires and 'solutions' in infertility accounts
given by women with 'atypical' sex development.
AB - Sociocultural meanings accorded to infertility, and rapid developments in
assisted reproductive technologies, have long been central concerns in feminist
and social scientific research. However, knowledge is scarce concerning how
individuals make sense of infertility when it is disclosed in adolescence, for
example as the result of an 'atypical' sex development, rather than as a result
of failed conception. This article examines how understandings of desires,
kinship and 'solutions' take shape and are negotiated in the accounts women give
of infertility resulting from 'atypical' sex development. Through a thematic
analysis it demonstrates how the interviewees described their desire for
relationships and connectedness, which they considered to be made possible
through pregnant embodiment, and details how these desires connected to a
preference for medical 'solutions'. Specifically, the article discusses how the
interviewees' accounts exemplifies how biological kinship can be 'done' without
giving precedence to genetics. By addressing the specificities of finding out
about infertility as a result of 'atypical' sex development, it furthermore
highlights gaps in the common medical definition of infertility. These findings
underscore the urgency of examining how definitions of infertility obscure
certain experiences and consequently limit affected individuals' access to
support and treatment. In conclusion, it is suggested that the article
contributes to a more positive discourse on infertility in feminist scholarship
by teasing out the temporal dimensions of how affected individuals 'make active
use' of assisted reproductive technologies to mitigate uncertainty and maintain
hope, while at the same time renegotiating dominant norms of kinship.
PMID- 28401812
TI - "Listen to your body": Participants' alternative to science in online health
discussions.
AB - We present a discursive psychological analysis of how the idiomatic expression
"Listen to Your Body" is deployed in online forum discussions about ADHD
medication and aspartame. The Listen to Your Body device allows participants to
demonstrate to others that they take their health seriously and for that reason
avoid scientific knowledge. They contrast Listen to Your Body with "blindly
following science," presenting Listen to Your Body as the more critical and,
therefore, more rational behavior. Instead of treating the idiomatic expression
as "anyone's knowledge," speakers and recipients compete for the right to own it.
It is discussed what these results mean for the role of and relation between
experiential knowledge ("lay expertise") and scientific expertise in online
discussions about health issues.
PMID- 28401813
TI - Epistemological challenges in contemporary Western healthcare systems exemplified
by people's widespread use of complementary and alternative medicine.
AB - Modern Western public healthcare systems offer predominantly publicly subsidized
healthcare traditionally based on biomedicine as the most important basis to cure
persons who suffer from disorders of somatic or psychiatric nature. To which
extent this epistemological position is suitable for this purpose is under
scientific debate and challenged by some people's personal understandings of
health and illness, their individual illness experiences and their decision
making. Current studies show decreasing levels of patient trust in Western public
healthcare and a widespread patient-initiated use of complementary and
alternative medicine which is often linked to unmet patient-defined healthcare
needs. Patients'/complementary and alternative medicine users' understandings of
their afflictions are often based on elements of biomedical knowledge as well as
embodied and experience-based knowledge. We believe this points to the need for a
phenomenologically and socially based understanding of health and illness. In
this article, we analyze challenges in contemporary healthcare systems,
exemplified by people's widespread use of complementary and alternative medicine
and based on three ways of understanding and relating to unhealth: disease (the
biomedical perspective), illness (the phenomenological perspective), and sickness
(the social perspective). In public healthcare systems aiming at involving
patients in treatment processes, acknowledging the coexistence of differing
epistemologies may be of great importance to define and reach goals of treatment
and compliance.
PMID- 28401814
TI - Public discourse on mental health and psychiatry: Representations in Swedish
newspapers.
AB - Mass media plays a central role in shaping public discourse on health and
illness. In order to examine media representations of mental health and expert
knowledge in this field, two major Swedish daily newspapers from the year 2009
were qualitatively analysed. Drawing on the theory of social representations, the
analysis focused on how issues concerning mental health and different
perspectives are represented. The results show how the concept of mental illness
is used in different and often taken-for-granted ways and how the distinction
between normal and pathological is a central underlying question. Laypersons'
perspectives are supplemented by views of professionals in the newspapers, where
signs of confidence and dependence on expert knowledge are juxtaposed with
critique and expressions of distrust. The newspaper discourse thus has salient
argumentative features and the way that conflicts are made explicit and issues
concerning authoritative knowledge are addressed indicates ambivalence towards
the authoritative role of expert knowledge concerning mental health. In this way,
the newspapers provide a complex epistemic context for everyday sense-making that
can be assumed to have implications for relations between laypersons and
professionals in the field of mental health.
PMID- 28401815
TI - To be or not to be sick and tired: Managing the visibility of HIV and HIV-related
fatigue.
AB - This article takes a new direction in exploring HIV-related fatigue by adopting a
qualitative interactionist approach. We analyse the social meanings attributed to
fatigue among people living with HIV in France, the social gains and losses of
its visibility and the social frames that condition its discursive and physical
expression. The two-part methodology combines grounded theory analysis of 50
transcribed unstructured interviews conducted across France and participant
observations within four HIV-related associations. Results reveal that the
visibility of fatigue is in part dependent on the visibility of this stigmatized
illness. The expression of fatigue is therefore closely linked with disclosure
and concerns about HIV stigma. The degree to which HIV and HIV-related fatigue
are rendered (in)visible also depends on structural factors including gender
prescriptions, as well as context effects such as the type of social or 'care'
relations involved in the social frame of interaction.
PMID- 28401816
TI - Clinical encounter and the logic of relationality: Reconfiguring bodies and
subjectivities in clinical relations.
AB - This article critically examines the significance of relational approaches for
sociological understandings of clinical interactions, relations and practices, by
exploring the ways in which relational theories and concepts have been employed
in the recent sociological accounts of clinical encounters to trouble the
classical dyadic models of clinical interaction and the related atomistic
conceptions of agency and accountability. Reading this work through the
theoretical contributions from feminist science studies scholarship, and
particularly the work of Donna Haraway and Karen Barad, the article proposes an
alternative understanding of clinical interactions, relations and practices,
where relations are conceived as constitutive of individuals (objects/bodies and
their attributes/identities), rather than being constituted by encounters between
individuals. Key for this understanding is the reconceptualisation of clinical
encounter as an apparatus of bodily production through which different agents
(patients, clinicians, diseases and healthcare services) are materialised and
enacted.
PMID- 28401817
TI - Contesting facts about wind farms in Australia and the legitimacy of adverse
health effects.
AB - The development of wind energy in Australia has been subject to ongoing public
debate and has been characterised by concerns over the health impacts of wind
turbines. Using discursive psychology, we examine 'wind turbine syndrome' as a
contested illness and analyse how people build and undermine divergent arguments
about wind-farm health effects. This article explores two facets of the dispute.
First, we consider how participants construct 'facts' about the health effects of
wind farms. We examine rhetorical resources used to construct wind farms as
harmful or benign. Second, we examine the local negotiation of the legitimacy of
health complaints. In the research interviews examined, even though interviewees
treat those who report experiencing symptoms from wind farms as having primary
rights to narrate their own experience, this epistemic primacy does not extend to
the ability to 'correctly' identify symptoms' cause. As a result, the legitimacy
of health complaints is undermined. Wind turbine syndrome is an example of a
contested illness that is politically controversial. We show how stake, interest
and legitimacy are particularly relevant for participants' competing descriptions
about the 'facts' of wind turbine health effects.
PMID- 28401818
TI - [Analysing gait in the GP's consulting room].
AB - Gait disorders are often seen in the general practitioner (GP)'s consulting room.
Orthopaedic or neurological problems may lead to abnormalities in gait. A careful
analysis is important to advice or refer the patient for additional diagnostics
or treatment. Basic gait analysis can be performed on any patient by applying a
systematic stepwise observation. This is illustrated here by three case reports.
This observation starts by looking at parameters such as walking speed, safety,
efficiency etc. Analysis of biomechanical pattern such as step frequency, stride
length and a detailed analysis of the different joint movements during the stance
and swing phase can subsequently be performed. This observation will be helpful
for the GP, guiding further examinations of function level such as mobility,
strength, or balance and resulting in adequate advice to the patient or referral
for additional diagnostics or treatment.
PMID- 28401819
TI - [A plea for selective use of the MammaPrint test].
AB - Recently, the results of the MINDACT study were published in The New England
Journal of Medicine. The authors conclude that the MammaPrint test can prevent
the use of chemotherapy in about 50% of breast cancer patients with a high-risk
clinical profile because of the presence of a genomic low risk MammaPrint. We
believe that the decision to use chemotherapy should not be based solely on the
outcome of the MammaPrint test, as is suggested by the authors, but also on
clinical factors, such as tumour size, nodal status and grade. We demonstrate
that the use of MammaPrint should be limited to those patients in whom the
survival benefit of chemotherapy on the 10-year survival rate is 2-4%, as
calculated with New Adjuvant Online, and assuming that patients consider an
absolute survival benefit of 3% or more due to chemotherapy worthwhile.
PMID- 28401820
TI - [A man with a curved deformity of the hand].
AB - A 63-year-old male was seen at the rheumatology outpatient clinic because of a
curved deformity of his left hand, with fixed flexion of the MCP joints and
hyperextension of the PIP and DIP joints. This so-called striatal hand, a feature
of Parkinson's disease, can easily be confused with rheumatoid arthritis or
Dupuytren's contracture.
PMID- 28401821
TI - [70-Gene signature as an aid to treatment decisions in early-stage breast
cancer].
AB - OBJECTIVE: The 70-gene signature test (MammaPrint) has been shown to improve
prediction of clinical outcome in women with early-stage breast cancer. We sought
to provide prospective evidence of the clinical utility of the addition of the 70
gene signature to standard clinical-pathological criteria in selecting patients
for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we
enrolled 6693 women with early-stage breast cancer and determined their genomic
risk (using the 70-gene signature) and their clinical risk (using a modified
version of Adjuvant! Online). Women at low clinical and genomic risk did not
receive chemotherapy, whereas those at high clinical and genomic risk did receive
such therapy. In patients with discordant risk results, either the genomic risk
or the clinical risk was used to determine the use of chemotherapy. The primary
goal was to assess whether, among patients with high-risk clinical features and a
low-risk gene-expression profile who did not receive chemotherapy, the lower
boundary of the 95% confidence interval for the rate of 5-year survival without
distant metastasis would be 92% (i.e., the noninferiority boundary) or higher.
RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk
and low genomic risk. At 5 years, the rate of survival without distant metastasis
in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not
receiving chemotherapy. The absolute difference in this survival rate between
these patients and those who received chemotherapy was 1.5 percentage points,
with the rate being lower without chemotherapy. Similar rates of survival without
distant metastasis were reported in the subgroup of patients who had estrogen
receptor-positive, human epidermal growth factor receptor 2-negative, and either
node-negative or node-positive disease. CONCLUSIONS: Among women with early-stage
breast cancer who were at high clinical risk and low genomic risk for recurrence,
the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5
year rate of survival without distant metastasis that was 1.5 percentage points
lower than the rate with chemotherapy. Given these findings, approximately 46% of
women with breast cancer who are at high clinical risk might not require
chemotherapy.
PMID- 28401822
TI - ?
AB - - The revised guideline 'Treatment of tobacco addiction and smoking cessation
support' offers health professionals a framework to provide evidence-based care
to patients who smoke, which should aid in reducing smoking prevalence and smoke
related morbidity and mortality.- Four topics of the guideline have been revised:
behavioural interventions, pharmacotherapy, e-health interventions and e
cigarettes. For the other topics, the recommendations from the 2009 version
remain unaltered.- It is important that health professionals offer a made-to
measure smoking cessation advice and apply a fit-for-purpose smoking cessation
intervention.- Nicotine replacement therapy remains the first-line
pharmacotherapy intervention and is most effective when combined with behavioural
intervention.- E-health interventions are particularly effective when they are
personalised and of an interactive nature, and when text messaging is
incorporated.- At present, e-cigarettes are not recommended as an aid to smoking
cessation.
PMID- 28401823
TI - [Socioeconomic differences and smoking: clear connections with implications for
tobacco policy].
AB - - Smoking is more common among people with a lower educational level,
professional qualifications and income. This is a major contributor to
inequalities in health and mortality.- Inequalities in smoking appear to have
their origin in early adolescence. Later in life these inequalities increase due
to differences in smoking cessation between higher and lower socioeconomic status
groups.- The inequalities in smoking cessation have already been explained in
great detail. The close association between smoking and a lower level of
education during adolescence is much less clear.- Evaluation of tobacco control
measures has shown differences in effectiveness between groups of higher and
lower socioeconomic status.- There are possibilities to allow measures to control
tobacco to be more effective in groups of a lower socioeconomic status. Higher
taxes on tobacco products should be accompanied by better access to professional
help to stop smoking.- For the early recognition of unforeseen reactions,
structural control measures should be monitored.
PMID- 28401824
TI - [Biosimilar registered despite the Netherlands opposing vote: greater uncertainty
about authorised drugs in the Netherlands].
AB - On 1 April 2016 the Committee for Medicinal Products for Human Use (CHMP) issued
a positive opinion on a new biological medicine, Flixabi(r), a biosimilar to
infliximab (Remicade(r)); however, in the appendix of the European Public
Assessment Report (EPAR) it appeared that an important minority (14 of 33 votes)
opposed this decision, among them the Netherlands representative. In an original
article, the Dutch Medicines Board (CBG-MEB) explained the reason for this
decision, but still allowed the drug on the market. This commentary states that
the EPAR is a 'snapshot', without the option for an update once the level of
uncertainty has been reduced and the drug is more acceptable. This confronts the
prescribing physician with an uncertain situation: which drugs can be safely
prescribed and which drugs may not be supported by the CBG-MEB?
PMID- 28401825
TI - The need for holistic management of behavioral disturbances in dementia.
AB - Dementia is now the leading cause of admission to residential aged care
facilities (RACF) in the developed world (Van Rensbergen and Nawrot, 2010), with
prevalence rates among residents estimated to be approximately 70% (Zimmerman et
al., 2014). In addition, dementia is now the 4th leading cause of death in high
income countries with this expected to rise to the 3rd leading cause of death by
2030 (World health Organization, 2015). Despite the prevalence of the condition,
the amount of teaching time devoted to dementia in medical school curricula
remains low and does not adequately prepare graduates for their work as doctors
(Tullo and Allan, 2011; Tullo and Gordon, 2013). As a consequence, many general
practitioners feel their level of confidence in managing behavioral and
psychological symptoms of dementia (BPSD) is very low (Buhagiar et al., 2011).
PMID- 28401826
TI - Establishing Theoretical Stability and Treatment Integrity for Motivational
Interviewing.
AB - BACKGROUND: There is increasing evidence claiming the effectiveness of
motivational interviewing (MI) in promoting behavioural change. However, ongoing
changes to MI theory and practice have implications for its transferability,
accessibility and for the validity of previous findings. Lack of practice
consistency may make its effectiveness difficult to evaluate. AIMS: This paper
explores the complexity of MI and issues in the development of evidence-based
practice in delivery, before describing issues related to practitioner
application. METHOD: Theoretical and practice developments over the last 30 years
are reviewed under the headings theory, practice and efficacy. Specifically,
developments across the three editions of the core MI texts are examined.
RESULTS: Findings from the literature suggest a lack of theoretical stability and
practice integrity, with recent fundamental changes to the underpinning structure
of MI. Issues relating to the transferability and acquisition of MI skills,
consistency of delivery and mechanisms underlying change are discussed.
CONCLUSIONS: The authors call for greater theoretical stability, more
transparency over how developments are based on theoretical principles and
empirical outcomes, and clearer guidance about how this informs practice
development and delivery of MI.
PMID- 28401827
TI - Attachment in the context of atypical caregiving.
PMID- 28401828
TI - Preoccupied but not dismissing attachment states of mind are associated with
nonsuicidal self-injury.
AB - In this investigation the factor structure of the Adult Attachment Interview was
studied in a partially at-risk sample of 120 young adults. More specifically, 60
participants had engaged in nonsuicidal self-injury (NSSI; 53 females, M age =
20.38 years), and 60 were non-self-injuring controls matched by age and sex.
Theoretically anticipated differential associations between preoccupied (but not
dismissing) states of mind and NSSI were then examined. Exploratory factor
analyses identified evidence for two weakly correlated state of mind dimensions
(i.e., dismissing and preoccupied) consistently identified in factor analyses of
normative-risk samples. As hypothesized, results further showed that preoccupied
(but not dismissing) states of mind were associated with NSSI behavior. Findings
support existing arguments suggesting that the regulatory strategy adults adopt
when discussing attachment-related experiences with primary caregivers,
particularly passive, angry, or unresolved discourse patterns, is uniquely
correlated with NSSI.
PMID- 28401829
TI - Attachment states of mind and inferred childhood experiences in maltreated and
comparison adolescents from low-income families.
AB - This paper reports the first large-sample investigation of the maltreatment
related correlates of low-income adolescents' narratives about their childhood
experiences with primary caregivers, as assessed with a modified version of the
Adult Attachment Interview (AAI) and based on official reports of abuse and
neglect (maltreated n = 214, nonmaltreated n = 140; M age = 16.7 years). Drawing
on factor-analytic and taxometric evidence indicating that AAI narratives vary
along two state of mind (i.e., dismissing and preoccupied) and two inferred
childhood experience (i.e., maternal and paternal) dimensions, here we
demonstrate that the experience of maltreatment, particularly when chronic, is
associated with increased risk for dismissing and preoccupied states of mind and
more negative inferred childhood experiences. Although such maltreatment-related
associations were generally not specific to any of the four AAI dimensions, the
experience of physical and/or sexual abuse was uniquely associated with
preoccupied states of mind and negative inferred paternal experiences even after
controlling for the other AAI dimensions. More extensive paternal perpetration of
maltreatment also was uniquely related to more negative inferred paternal
experiences.
PMID- 28401830
TI - Childhood abuse and neglect and insecure attachment states of mind in adulthood:
Prospective, longitudinal evidence from a high-risk sample.
AB - The present report used data from the Minnesota Longitudinal Study of Risk and
Adaptation to investigate the factor structure and childhood abuse and/or neglect
related antecedents of adults' attachment states of mind in a high-risk sample.
Adult Attachment Interviews (AAIs) were collected when participants were age 26
years (N = 164) and Current Relationship Interviews (CRIs) were collected from
participants (N = 116) and their romantic partners when target participants were
between ages 20 and 28 years (M = 25.3 years). For both the AAI and the CRI,
exploratory factor analyses revealed that (a) attachment state of mind scales
loaded on two weakly correlated dimensions reflecting dismissing and preoccupied
states of mind and (b) ratings of unresolved discourse loaded on the same factor
as indicators of preoccupied states of mind. Experiencing any subtype of abuse
and/or neglect, especially during multiple developmental periods, and
experiencing multiple subtypes of abuse and/or neglect during childhood were
associated with risk for preoccupied (but not dismissing) AAI states of mind
regarding childhood relationships with caregivers. Analyses focused on the
particular subtypes, and perpetrators indicated that the predictive significance
of childhood abuse/neglect for adult's AAI preoccupied states of mind was
specific to experiences of abuse (but not neglect) perpetrated by primary
caregivers. In addition, experiencing chronic or multiple subtypes of childhood
abuse and/or neglect increased risk for dismissing (but not preoccupied) CRI
states of mind regarding adult romantic partners.
PMID- 28401832
TI - Attachment in young children with incarcerated fathers.
AB - The present study examined young children's attachment behaviors during paternal
incarceration and reported on initial validity of a new measure used to rate
children's attachment-related behaviors and emotions during visits in a
corrections setting. Seventy-seven children, age 2 to 6 years, and their jailed
fathers and current caregivers participated in the home visit portion of the
study, whereas 28 of these children participated in the jail visit. The results
indicated that 27% of children witnessed the father's crime and 22% of children
witnessed the father's arrest, with most children who witnessed these events
exhibiting extreme distress; children who witnessed these events were more likely
to have insecure attachments to their caregivers. Consistent with attachment
theory and research, caregivers who exhibited more sensitivity and responsivity
during interactions with children and those who provided more stimulating,
responsive, learning-oriented home environments had children who were more likely
to have secure attachments (measured with the Attachment Q-Sort). We also found
preliminary evidence for the validity of our new measure, the Jail Prison
Observation Checklist, in that children's attachment-related behaviors and
emotions during the jail visit correlated with their attachment security observed
in the home. Our observations indicate that, in certain contexts, noncontact
visits with incarcerated parents can be stressful for children and that
children's caregivers may play a significant role during these visits.
PMID- 28401831
TI - Attachment states of mind among internationally adoptive and foster parents.
AB - The first aim of the current study was to examine the latent structure of
attachment states of mind as assessed by the Adult Attachment Interview (AAI)
among three groups of parents of children at risk for insecure attachments:
parents who adopted internationally (N = 147), foster parents (N = 300), and
parents living in poverty and involved with Child Protective Services (CPS; N =
284). Confirmatory factor analysis indicated the state of mind rating scales
loaded on two factors reflecting adults' preoccupied and dismissing states of
mind. Taxometric analyses indicated the variation in adults' preoccupied states
of mind was more consistent with a dimensional than a categorical model, whereas
results for dismissing states of mind were indeterminate. The second aim was to
examine the degree to which the attachment states of mind of internationally
adoptive and foster parents differ from those of poverty/CPS-referred parents and
low-risk parents. After controlling for parental age, sex, ethnicity, and
socioeconomic status, (a) internationally adoptive parents had lower scores on
the dismissing dimension than the sample of community parents described by
Haltigan, Leerkes, Supple, and Calkins (2014); (b) foster parents did not differ
from community parents on either the dismissing or the preoccupied AAI dimension;
and (c) both internationally adoptive and foster parents had lower scores on the
preoccupied dimension than poverty/CPS-referred parents. Analyses using the
traditional AAI categories provided convergent evidence that (a) internationally
adoptive parents were more likely to be classified as having an autonomous state
of mind than low-risk North American mothers based on Bakermans-Kranenburg and
van IJzendoorn's (2009) meta-analytic estimates, (b) the rates of autonomous
states of mind did not differ between foster and low-risk parents, and
PMID- 28401833
TI - Atypical dimensions of caregiver-adolescent interaction in an economically
disadvantaged sample.
AB - The Goal-Corrected Partnership Adolescent Coding System (GPACS) has shown promise
in assessing a secure as well as three atypical patterns of parent-adolescent
interaction during a conflict discussion. The current study of 186 economically
disadvantaged families examines the degree to which four GPACS patterns:
secure/collaborative, hostile/punitive, role confused, and disoriented,
prospectively predict adolescents' social competence and maladaptive behavior
(internalizing, externalizing, and risk behaviors) at age 15 years after
controlling for these social behaviors at age 13 years and contemporaneous GPACS
scores. Adolescents from secure/collaborative dyads at age 13 were more likely to
have a secure state of mind in the Adult Attachment Interview at age 15 and
showed higher levels of teachers' ratings of empathy and lower levels of
teachers' ratings of externalizing behaviors at age 15 years. Adolescents in
disoriented dyads showed higher levels of teacher-rated internalizing problems,
while male adolescents in role confused dyads reported higher levels of
involvement in risk behaviors, including unprotected sexual activity and
substance use problems.
PMID- 28401834
TI - A process model of the implications of spillover from coparenting conflicts into
the parent-child attachment relationship in adolescence.
AB - Drawing on a two-wave, multimethod, multi-informant design, this study provides
the first test of a process model of spillover specifying why and how disruptions
in the coparenting relationship influence the parent-adolescent attachment
relationship. One hundred ninety-four families with an adolescent aged 12-14 (M
age = 12.4) were followed for 1 year. Mothers and adolescents participated in two
experimental tasks designed to elicit behavioral expressions of parent and
adolescent functioning within the attachment relationship. Using a novel
observational approach, maternal safe haven, secure base, and harshness (i.e.,
hostility and control) were compared as potential unique mediators of the
association between conflict in the coparenting relationship and adolescent
problems. Path models indicated that, although coparenting conflicts were broadly
associated with maternal parenting difficulties, only secure base explained the
link to adolescent adjustment. Adding further specificity to the process model,
maternal secure base support was uniquely associated with adolescent adjustment
through deficits in adolescents' secure exploration. Results support the
hypothesis that coparenting disagreements undermine adolescent adjustment in
multiple domains specifically by disrupting mothers' ability to provide a
caregiving environment that supports adolescent exploration during a
developmental period in which developing autonomy is a crucial stage-salient
task.
PMID- 28401835
TI - Brain activity and infant attachment history in young men during loss and reward
processing.
AB - There is now ample evidence that the quality of early attachment experiences
shapes expectations for supportive and responsive care and ultimately serves to
scaffold adaptation to the salient tasks of development. Nonetheless, few studies
have identified neural mechanisms that might give rise to these associations.
Using a moderately large sample of low-income male participants recruited during
infancy (N = 171), we studied the predictive significance of attachment
insecurity and disorganization at age 18 months (as measured in the Strange
Situation Procedure) for patterns of neural activation to reward and loss at age
20 years (assessed during a reward-based task as part of a functional magnetic
resonance imaging scan). Results indicated that individuals with a history of
insecure attachment showed hyperactivity in (a) reward- and emotion-related
(e.g., basal ganglia and amygdala) structures and (b) emotion regulation and self
referential processing (cortical midline structures) in response to positive and
negative outcomes (and anticipation of those outcomes). Further, the neural
activation of individuals with a history of disorganized attachment suggested
that they had greater emotional reactivity in anticipation of reward and employed
greater cognitive control when negative outcomes were encountered. Overall,
results suggest that the quality of early attachments has lasting impacts on
brain function and reward processing.
PMID- 28401836
TI - Insensitive parenting may accelerate the development of the amygdala-medial
prefrontal cortex circuit.
AB - This study examined whether the association between age and amygdala-medial
prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old
children is correlated with parental care. Resting-state functional magnetic
resonance imaging scans were acquired from 124 children of the Generation R Study
who at 4 years old had been observed interacting with their parents to assess
maternal and paternal sensitivity. Amygdala functional connectivity was assessed
using a general linear model with the amygdalae time series as explanatory
variables. Higher level analyses assessing Sensitivity * Age as well as
exploratory Sensitivity * Age * Gender interaction effects were performed
restricted to voxels in the mPFC. We found significant Sensitivity * Age
interaction effects on amygdala-mPFC connectivity. Age was related to stronger
amygdala-mPFC connectivity in children with a lower combined parental sensitivity
score (b = 0.11, p = .004, b = 0.06, p = .06, right and left amygdala,
respectively), but not in children with a higher parental sensitivity score, (b =
-0.07, p = .12, b = -0.06, p = .12, right and left amygdala, respectively). A
similar effect was found for maternal sensitivity, with stronger amygdala-mPFC
connectivity in children with less sensitive mothers. Exploratory (parental,
maternal, paternal) Sensitivity * Age * Gender interaction analyses suggested
that this effect was especially pronounced in girls. Amygdala-mPFC resting-state
functional connectivity has been shown to increase from age 10.5 years onward,
implying that the positive association between age and amygdala-mPFC connectivity
in 6- to 10-year-old children of less sensitive parents represents accelerated
development of the amygdala-mPFC circuit.
PMID- 28401837
TI - New insight on intergenerational attachment from a relationship-based analysis.
AB - Research on attachment transmission has focused on variable-centered analyses,
where hypotheses are tested by examining linear associations between variables.
The purpose of this study was to apply a relationship-centered approach to data
analysis, where adult states of mind, maternal sensitivity, and infant attachment
were conceived as being three components of a single, intergenerational
relationship. These variables were assessed in 90 adolescent and 99 adult mother
infant dyads when infants were 12 months old. Initial variable-centered analyses
replicated the frequently observed associations between these three core
attachment variables. Relationship-based, latent class analyses then revealed
that the most common pattern among young mother dyads featured maternal
unresolved trauma, insensitive interactive behavior, and disorganized infant
attachment (61%), whereas the most prevalent adult mother dyad relationship
pattern involved maternal autonomy, sensitive maternal behavior, and secure
infant attachment (59%). Three less prevalent relationship patterns were also
observed. Moderation analyses revealed that the adolescent-adult mother
distinction differentiated between secure and disorganized intergenerational
relationship patterns, whereas experience of traumatic events distinguished
between disorganized and avoidant patterns. Finally, socioeconomic status
distinguished between avoidant and secure patterns. Results emphasize the value
of a relationship-based approach, adding an angle of understanding to the study
of attachment transmission.
PMID- 28401838
TI - Poverty, early care, and stress reactivity in adolescence: Findings from a
prospective, longitudinal study in South Africa.
AB - A considerable body of evidence suggests that early caregiving may affect the
short-term functioning and longer term development of the hypothalamic-pituitary
adrenocortical axis. Despite this, most research to date has been cross-sectional
in nature or restricted to relatively short-term longitudinal follow-ups. More
important, there is a paucity of research on the role of caregiving in low- and
middle-income countries, where the protective effects of high-quality care in
buffering the child's developing stress regulation systems may be crucial. In
this paper, we report findings from a longitudinal study (N = 232) conducted in
an impoverished periurban settlement in Cape Town, South Africa. We measured
caregiving sensitivity and security of attachment in infancy and followed
children up at age 13 years, when we conducted assessments of hypothalamus
pituitary-adrenocortical axis reactivity, as indexed by salivary cortisol during
the Trier Social Stress Test. The findings indicated that insecure attachment was
predictive of reduced cortisol responses to social stress, particularly in boys,
and that attachment status moderated the impact of contextual adversity on stress
responses: secure children in highly adverse circumstances did not show the
blunted cortisol response shown by their insecure counterparts. Some evidence was
found that sensitivity of care in infancy was also associated with cortisol
reactivity, but in this case, insensitivity was associated with heightened
cortisol reactivity, and only for girls. The discussion focuses on the
potentially important role of caregiving in the long-term calibration of the
stress system and the need to better understand the social and biological
mechanisms shaping the stress response across development in low- and middle
income countries.
PMID- 28401840
TI - Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the
associations of FKBP5 genotype and resistant attachment with stress regulation.
AB - The parent-child attachment relationship plays an important role in the
development of the infant's stress regulation system. However, genetic and
epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA
methylation have also been associated with hypothalamus-pituitary-adrenal axis
functioning. In the current study, we examined how parent-child dyadic regulation
works in concert with genetic and epigenetic aspects of stress regulation. We
study the associations of attachment, extreme maternal insensitivity, FKBP5
single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol
reactivity to the Strange Situation Procedure in 298 14-month-old infants. The
results indicate that FKBP5 methylation moderates the associations of FKBP5
genotype and resistant attachment with cortisol reactivity. We conclude that the
inclusion of epigenetics in the field of developmental psychopathology may lead
to a more precise picture of the interplay between genetic makeup and parenting
in shaping stress reactivity.
PMID- 28401839
TI - Caregiver maltreatment causes altered neuronal DNA methylation in female rodents.
AB - Negative experiences with a caregiver during infancy can result in long-term
changes in brain function and behavior, but underlying mechanisms are not well
understood. It is our central hypothesis that brain and behavior changes are
conferred by early childhood adversity through epigenetic changes involving DNA
methylation. Using a rodent model of early-life caregiver maltreatment (involving
exposure to an adverse caregiving environment for postnatal days 1-7), we have
previously demonstrated abnormal methylation of DNA associated with the brain
derived neurotrophic factor (Bdnf) gene in the medial prefrontal cortex (mPFC) of
adult rats. The aim of the current study was to characterize Bdnf DNA methylation
in specific cell populations within the mPFC. In the prefrontal cortex, there is
approximately twice as many neurons as glia, and studies have recently shown
differential and distinctive DNA methylation patterns in neurons versus
nonneurons. Here, we extracted nuclei from the mPFC of adult animals that had
experienced maltreatment and used fluorescence-activated cell sorting to isolate
cell types before performing bisulfite sequencing to estimate methylation of
cytosine-guanine sites. Our data indicate that early-life stress induced
methylation of DNA associated with Bdnf IV in a cell-type and sex-specific
manner. Specifically, females that experienced early-life maltreatment exhibited
greater neuronal cytosine-guanine methylation compared to controls, while no
changes were detected in Bdnf methylation in males regardless of cell type. These
changes localize the specificity of our previous findings to mPFC neurons and
highlight the capacity of maltreatment to cause methylation changes that are
likely to have functional consequences for neuronal function.
PMID- 28401841
TI - Positive valence bias and parent-child relationship security moderate the
association between early institutional caregiving and internalizing symptoms.
AB - Institutional caregiving is associated with significant deviations from species
expected caregiving, altering the normative sequence of attachment formation and
placing children at risk for long-term emotional difficulties. However, little is
known about factors that can promote resilience following early institutional
caregiving. In the current study, we investigated how adaptations in affective
processing (i.e., positive valence bias) and family-level protective factors
(i.e., secure parent-child relationships) moderate risk for internalizing
symptoms in previously institutionalized (PI) youth. Children and adolescents
with and without a history of institutional care performed a laboratory-based
affective processing task and self-reported measures of parent-child relationship
security. PI youth were more likely than comparison youth to show positive
valence biases when interpreting ambiguous facial expressions. Both positive
valence bias and parent-child relationship security moderated the association
between institutional care and parent-reported internalizing symptoms, such that
greater positive valence bias and more secure parent-child relationships
predicted fewer symptoms in PI youth. However, when both factors were tested
concurrently, parent-child relationship security more strongly moderated the link
between PI status and internalizing symptoms. These findings suggest that both
individual-level adaptations in affective processing and family-level factors of
secure parent-child relationships may ameliorate risk for internalizing
psychopathology following early institutional caregiving.
PMID- 28401842
TI - Testing the limits: Extending attachment-based intervention effects to infant
cognitive outcome and parental stress.
AB - Using a sample of 41 infants and toddlers (21 interventions, 20 controls) who
were neglected or at serious risk for neglect, this randomized clinical trial
examined the efficacy of a parent-child attachment-based video-feedback
intervention on parental sensitivity, parental stress, and child
mental/psychomotor development. Results showed that following the 8-week
intervention, scores for maternal sensitivity and child mental and psychomotor
development were higher in the intervention group than in the control group. The
intervention appears to have no effect on self-reports of stress. All parents
report lower levels of stress postintervention; however, when defensive
responding is not considered (i.e., extremely low score of parental stress),
parents in the control group report somewhat lower scores, raising questions as
to the significance of this finding. Considering the small nature of our sample,
replication of the present results is needed. Nevertheless, the present findings
contribute to the burgeoning literature suggesting that the early attachment
relationship provides an important context that influences developmental outcome
in different spheres and raises questions as to how such intervention strategies
may or may not affect the subjective experience of parenting.
PMID- 28401843
TI - Circle of Security-Parenting: A randomized controlled trial in Head Start.
AB - Although evidence shows that attachment insecurity and disorganization increase
risk for the development of psychopathology (Fearon, Bakermans-Kranenburg, van
IJzendoorn, Lapsley, & Roisman, 2010; Groh, Roisman, van IJzendoorn, Bakermans
Kranenburg, & Fearon, 2012), implementation challenges have precluded
dissemination of attachment interventions on the broad scale at which they are
needed. The Circle of Security-Parenting Intervention (COS-P; Cooper, Hoffman, &
Powell, 2009), designed with broad implementation in mind, addresses this gap by
training community service providers to use a manualized, video-based program to
help caregivers provide a secure base and a safe haven for their children. The
present study is a randomized controlled trial of COS-P in a low-income sample of
Head Start enrolled children and their mothers. Mothers (N = 141; 75
intervention, 66 waitlist control) completed a baseline assessment and returned
with their children after the 10-week intervention for the outcome assessment,
which included the Strange Situation. Intent to treat analyses revealed a main
effect for maternal response to child distress, with mothers assigned to COS-P
reporting fewer unsupportive (but not more supportive) responses to distress than
control group mothers, and a main effect for one dimension of child executive
functioning (inhibitory control but not cognitive flexibility when maternal age
and marital status were controlled), with intervention group children showing
greater control. There were, however, no main effects of intervention for child
attachment or behavior problems. Exploratory follow-up analyses suggested
intervention effects were moderated by maternal attachment style or depressive
symptoms, with moderated intervention effects emerging for child attachment
security and disorganization, but not avoidance; for inhibitory control but not
cognitive flexibility; and for child internalizing but not externalizing behavior
problems. This initial randomized controlled trial of the efficacy of COS-P sets
the stage for further exploration of "what works for whom" in attachment
intervention.
PMID- 28401844
TI - Signs of reactive attachment disorder and disinhibited social engagement disorder
at age 12 years: Effects of institutional care history and high-quality foster
care.
AB - Two disorders of attachment have been consistently identified in some young
children following severe deprivation in early life: reactive attachment disorder
and disinhibited social engagement disorder. However, less is known about whether
signs of these disorders persist into adolescence. We examined signs of reactive
attachment disorder and disinhibited social engagement disorder at age 12 years
in 111 children who were abandoned at or shortly after birth and subsequently
randomized to care as usual or to high-quality foster care, as well as in 50
comparison children who were never institutionalized. Consistent with
expectations, those who experienced institutional care in early life had more
signs of reactive attachment disorder and disinhibited social engagement disorder
at age 12 years than children never institutionalized. In addition, using a
conservative intent-to-treat approach, those children randomized to foster care
had significantly fewer signs of reactive attachment disorder and disinhibited
social engagement disorder than those randomized to care as usual. Analyses
within the ever institutionalized group revealed no effects of the age of
placement into foster care, but number of caregiving disruptions experienced and
the percentage of the child's life spent in institutional care were significant
predictors of signs of attachment disorders assessed in early adolescence. These
findings indicate that adverse caregiving environments in early life have
enduring effects on signs of attachment disorders, and provide further evidence
that high-quality caregiving interventions are associated with reductions in both
reactive attachment disorder and disinhibited social engagement disorder.
PMID- 28401845
TI - Parent-child intervention decreases stress and increases maternal brain activity
and connectivity during own baby-cry: An exploratory study.
AB - Parental responses to their children are crucially influenced by stress. However,
brain-based mechanistic understanding of the adverse effects of parenting stress
and benefits of therapeutic interventions is lacking. We studied maternal brain
responses to salient child signals as a function of Mom Power (MP), an attachment
based parenting intervention established to decrease maternal distress. Twenty
nine mothers underwent two functional magnetic resonance imaging brain scans
during a baby-cry task designed to solicit maternal responses to child's or
self's distress signals. Between scans, mothers were pseudorandomly assigned to
either MP (n = 14) or control (n = 15) with groups balanced for depression.
Compared to control, MP decreased parenting stress and increased child-focused
responses in social brain areas highlighted by the precuneus and its functional
connectivity with subgenual anterior cingulate cortex, which are key components
of reflective self-awareness and decision-making neurocircuitry. Furthermore,
over 13 weeks, reduction in parenting stress was related to increasing child-
versus self-focused baby-cry responses in amygdala-temporal pole functional
connectivity, which may mediate maternal ability to take her child's perspective.
Although replication in larger samples is needed, the results of this first
parental-brain intervention study demonstrate robust stress-related brain
circuits for maternal care that can be modulated by psychotherapy.
PMID- 28401846
TI - Proof of concept of a mind-mindedness intervention for mothers hospitalized for
severe mental illness.
AB - Studies 1 and 2 investigated how maternal severe mental illness (SMI) related to
mothers' mind-mindedness (appropriate and nonattuned mind-related comments).
Study 1 showed that mothers with SMI (n = 50) scored lower than psychologically
well mothers for both appropriate and nonattuned comments, whereas mothers with
SMI in Study 2 (n = 22) had elevated levels of nonattuned comments. Study 2 also
tested the efficacy of a single-session video-feedback intervention to facilitate
mind-mindedness in mothers with SMI. The intervention was associated with a
decrease in nonattuned comments, such that on discharge, mothers did not differ
from psychologically well controls. Study 3 assessed infant-mother attachment
security in a small subset of intervention-group mothers from Study 2 (n = 9) and
a separate group of standard care mothers (n = 30) at infant mean age 17.1 months
(SD = 2.1). Infants whose mothers completed the intervention were more likely to
be securely attached and less likely to be classified as insecure-disorganized
than those of mothers who received standard care. We conclude that a single
session of video-feedback to facilitate mind-mindedness in mothers with SMI may
have benefits for mother-infant interaction into the second year of life.
PMID- 28401847
TI - Enhancing executive functioning among toddlers in foster care with an attachment
based intervention.
AB - Young children in foster care often experience adversity, such as maltreatment
and lack of stability in early caregiving relationships. As a result, these
children are at risk for a range of problems, including deficits in executive
functioning. The Attachment and Biobehavioral Catch-up for Toddlers (ABC-T)
intervention was designed to help foster parents behave in ways that promote the
development of young children's emerging self-regulatory capabilities.
Participants included 173 parent-toddler dyads in three groups: foster families
that were randomly assigned to receive either the ABC-T intervention (n = 63) or
a control intervention (n = 58), as well as low-risk parent-toddler dyads from
intact families (n = 52). At a follow-up conducted when children were
approximately 48 months old, children's executive functioning abilities were
assessed with the attention problems scale of the Child Behavior Checklist
(Achenbach & Rescorla, 2000) and a graded version of the Dimensional Change Card
Sort developed for preschoolers (Beck, Schaefer, Pang, & Carlson, 2011). Results
showed that foster children whose parents received the ABC-T intervention and low
risk children never placed in foster care had fewer parent-reported attention
problems and demonstrated greater cognitive flexibility during the Dimensional
Change Card Sort than foster children whose parents received the control
intervention. These results indicate that an attachment-based intervention
implemented among toddlers in foster care is effective in enhancing children's
executive functioning capabilities.
PMID- 28401848
TI - Attachment security mediates the longitudinal association between child-parent
psychotherapy and peer relations for toddlers of depressed mothers.
AB - Numerous investigations have demonstrated that child-parent psychotherapy (CPP)
promotes secure attachment between mothers and offspring. However, the role of
postintervention attachment security as it relates to long-term child outcomes
has never been evaluated. The present study therefore examined postintervention
attachment status as a mediator of the association between CPP for depressed
mothers and their offspring and subsequent peer relations among offspring.
Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or
to a control group (n = 55). A prior investigation with this sample indicated
that offspring who received CPP attained significantly higher rates of secure
attachment postintervention, whereas insecure attachment continued to predominate
for offspring in the control group. The present study examined follow-up data of
teachers' reports on participants' competence with classroom peers when they were
approximately 9 years old. Findings indicated that children who received CPP were
more likely to evidence secure attachments at postintervention, which in turn was
associated with more positive peer relationships at age 9.
PMID- 28401850
TI - Mothering From the Inside Out: Results of a second randomized clinical trial
testing a mentalization-based intervention for mothers in addiction treatment.
AB - Mothers with histories of alcohol and drug addiction have shown greater
difficulty parenting young children than mothers with no history of substance
misuse. This study was the second randomized clinical trial testing the efficacy
of Mothering From the Inside Out (MIO), a 12-week mentalization-based individual
therapy designed to address psychological deficits commonly associated with
chronic substance use that also interfere with the capacity to parent young
children. Eighty-seven mothers caring for a child between 11 and 60 months of age
were randomly assigned to receive 12 sessions of MIO versus 12 sessions of parent
education (PE), a psychoeducation active control comparison. Maternal reflective
functioning, representations of caregiving, mother-child interaction quality, and
child attachment were evaluated at baseline and posttreatment and 3-month follow
up. Mother-child interaction quality was assessed again at 12-month follow-up. In
comparison with PE mothers, MIO mothers demonstrated a higher capacity for
reflective functioning and representational coherence at posttreatment and 3
month follow-up. At 12-month follow-up, compared to PE cohorts, MIO mothers
demonstrated greater sensitivity, their children showed greater involvement, and
MIO dyads showed greater reciprocity. As addiction severity increased, MIO also
appeared to serve as a protective factor for maternal reflective functioning,
quality of mother-child interactions, and child attachment status. Results
demonstrate the promise of mentalization-based interventions provided concomitant
with addiction treatment for mothers and their young children.
PMID- 28401849
TI - Developmental cascade effects of interpersonal psychotherapy for depressed
mothers: Longitudinal associations with toddler attachment, temperament, and
maternal parenting efficacy.
AB - Using a developmental cascades framework, the current study investigated whether
treating maternal depression via interpersonal psychotherapy (IPT) may lead to
more widespread positive adaptation for offspring and mothers including benefits
to toddler attachment and temperament, and maternal parenting self-efficacy. The
participants (N = 125 mother-child dyads; mean mother age at baseline = 25.43
years; 54.4% of mothers were African American; mean offspring age at baseline =
13.23 months) were from a randomized controlled trial of IPT for a sample of
racially and ethnically diverse, socioeconomically disadvantaged mothers of
infants. Mothers were randomized to IPT (n = 97) or an enhanced community
standard control group (n = 28). The results of complier average causal effect
modeling showed that engagement with IPT led to significant decreases in maternal
depressive symptoms at posttreatment. Moreover, reductions in maternal depression
posttreatment were associated with less toddler disorganized attachment
characteristics, more adaptive maternal perceptions of toddler temperament, and
improved maternal parenting efficacy 8 months following the completion of
treatment. Our findings contribute to the emerging literature documenting the
potential benefits to children of successfully treating maternal depression.
Alleviating maternal depression appears to initiate a cascade of positive
adaptation among both mothers and offspring, which may alter the well-documented
risk trajectory for offspring of depressed mothers.
PMID- 28401851
TI - Assessing a change mechanism in a randomized home-visiting trial: Reducing
disrupted maternal communication decreases infant disorganization.
AB - Although randomized interventions trials have been shown to reduce the incidence
of disorganized attachment, no studies to date have identified the mechanisms of
change responsible for such reductions. Maternal sensitivity has been assessed in
various studies and shown to change with intervention, but in the only study to
formally assess mediation, changes in maternal sensitivity did not mediate
changes in infant security of attachment (Cicchetti, Rogosch, & Toth, 2006).
Primary aims of the current randomized controlled intervention trial in a high
risk population were to fill gaps in the literature by assessing whether the
intervention (a) reduced disorganization, (b) reduced disrupted maternal
communication, and (c) whether reductions in disrupted maternal communication
mediated changes in infant disorganization. The results indicated that, compared
to controls (n = 52), both infant disorganization and disrupted maternal
communication were significantly reduced in the intervention group (n = 65) that
received regular home-visiting during pregnancy and the first year of life.
Furthermore, reductions in disrupted maternal communication partially accounted
for the observed reductions in infant disorganization compared to randomized
controls. The results are discussed in relation to the societal cost
effectiveness of early attachment-informed interventions for mothers and infants,
as well as the importance of formally assessing underlying mechanisms of change
in order to improve and appropriately target preventive interventions.
PMID- 28401852
TI - T-helper type 1-T-helper type 2 shift and nasal remodeling after fine particulate
matter exposure in a rat model of allergic rhinitis.
AB - BACKGROUND: Exposure to fine particulate matter (particulate matter <=2.5 MUm
[PM2.5]) increases the risk of allergic rhinitis (AR), but the underlying
mechanisms remains unclear. Thus, we investigated the roles of T-helper (Th)1-Th2
cytokines and nasal remodeling after ambient PM2.5 exposure in a rat model of AR.
METHODS: Female Sprague-Dawley rats were randomized into six groups: a negative
control group, a group of healthy rats exposed to 3000 MUg/m3 PM2.5, an ovalbumin
(OVA) induced AR model, and three PM2.5-exacerbated AR groups exposed to three
different concentrations (200, 1000, and 3000 MUg/m3) of PM2.5 for 30 days via
inhalation. Nasal symptoms, levels of Th1-Th2 cytokines, the degree of
eosinophilia in nasal lavage fluid (NLF), and the messenger RNA (mRNA)
expressions of transcription factors GATA-3 and T-bet in the nasal mucosa were
measured in each individual rat. Hyperplasia of globet cells and collagen
deposition were examined by histology. RESULTS: PM2.5 significantly increased the
number of sneezes and nasal rubs in rats with AR. PM2.5 also significantly
decreased interferon gamma and increased interleukin (IL) 4 and IL-13 expressions
as well as the number of eosinophils in NLF. The mRNA expression of GATA-3 in the
nasal mucosa of rats with AR was upregulated by PM2.5, whereas T-bet was
significantly downregulated. Statistically significant differences in OVA
specific serum immunoglobulin E, goblet cell hyperplasia, collagen deposition,
and transforming growth factor beta 1 levels were observed between the PM2.5
exacerbated AR groups and the AR model group. CONCLUSION: Analysis of our data
indicated that an increase in the immune response with Th2 polarization and the
development of nasal remodeling may be the immunotoxic mechanisms behind the
exacerbation of AR after exposure to PM2.5.
PMID- 28401853
TI - For LV pacing, four is greater than two.
PMID- 28401854
TI - Inappropriate implantable cardioverter-defibrillator shocks in Brugada syndrome:
Pattern in primary and secondary prevention.
AB - BACKGROUND: Inappropriate implantable cardioverter-defibrillator (ICD) shocks is
a common complication in Brugada syndrome. However, the incidence in recipients
of ICD for primary and secondary prevention is unknown. METHOD AND RESULTS: We
compared the rate of inappropriate shocks in patients with Brugada syndrome that
had an ICD for primary and secondary prevention. We studied 51 patients, 86.5% of
whom were males. Their mean age at diagnosis was 47 +/- 11 years. Eighteen (35%)
were asymptomatic, while 25 (49%) experienced syncope prior to implantation.
Eight (16%) patients were resuscitated from ventricular fibrillation before
implantation. During a mean follow-up of 78 +/- 46 months, none of the
asymptomatic patients experienced appropriate therapy, whereas 21.6% of
symptomatic patients had >=1 shock. Inappropriate shock occurred in 7 (13.7%)
patients, with a mean IS of 6.57 +/- 6.94 shocks per patient occurring 16.14 +/-
10.38 months after implantation. There was a trend towards higher incidence of
inappropriate shock in the asymptomatic group (p = 0.09). The interval from
implantation to inappropriate shock occurrence was 13.91 +/- 12.98 months. The
risk of IS at 3 years was 13.7%, which eventually plateaued over the time.
CONCLUSION: Inappropriate shock is common in Brugada syndrome during the early
periods after an ICD implantation, and seems to be more likely in asymptomatic
patients. This finding may warrant a review of the indications for ICD
implantation, especially in the young and apparently healthy population of
patients with Brugada syndrome.
PMID- 28401855
TI - Brugada syndrome and calcium channel mutation in a patient with congenital deaf
mutism.
AB - To the best of our knowledge, for the first time in the literature, we described
a congenitally deaf-mute patient with Brugada syndrome (BrS) in whom a mutation
in L-type Ca+2 channel [CACNA1C (Cav1.2alpha1)] was identified.
PMID- 28401856
TI - Unusual lead helix damage due to 'Selective' Reel syndrome.
AB - Oblivious manipulation of the device by the patient is referred to as
"Twiddler's" syndrome. It is characterized by the coiling of the pacemaker lead
due to the rotation of the pacemaker generator on its long axis. However, the
rotation of the pacemaker generator on its transverse axis with subsequent
coiling of the pacemaker leads around the pulse generator is called as ''Reel
syndrome''. In this case, we present a 69-year-old patient with 'selective' Reel
syndrome and postulate the possible explanation for damaged atrial lead.
PMID- 28401857
TI - Premature complexes and pauses.
PMID- 28401858
TI - Wide QRS tachycardia. What is the mechanism?
PMID- 28401859
TI - Dr. Mark Eric Josephson (1943-2017).
PMID- 28401860
TI - Lead related complications in quadripolar versus bipolar left ventricular leads.
AB - BACKGROUND: Quadripolar left ventricular (LV) leads are capable of pacing from
four different electrodes which allows for easier and more stable intra-operative
lead positioning with optimal pacing parameters. We therefore investigated the
rate of combined intra-operative and post-operative LV lead related events in
quadripolar vs. bipolar LV lead cardiac resynchronization therapy (CRT)
recipients in the real world setting. METHODS: We retrospectively collected data
for N = 1441 patients at our institution implanted with quadripolar (n = 292) or
bipolar (n = 1149) LV leads from 2012 to 2014 and followed them to the primary
end-point of composite lead outcome defined as intra-operative lead implant
failure or post-operative lead dislodgement or deactivations. RESULTS: Patients
implanted with a quadripolar lead were younger (70.6 +/- 11.4 vs 72.5 +/- 11.6, p
= 0.014) and had higher incidence of diabetes (41.8% vs 32.8%, p = 0.004)
compared to those with bipolar leads. All other baseline characteristics were
comparable. Patients implanted with a quadripolar were significantly less likely
to reach the primary endpoint in the first 12 months after LV lead implantation
(Hazard Ratio 0.22, 95% Confidence Interval 0.08-0.60, p = 0.001). There were no
differences between the two groups in rates of hospitalization for any cause or
in mortality. CONCLUSION: In this real world study, quadripolar LV leads have
significantly lower rates of implantation failure and post-operative lead
dislodgement or deactivation. These results have important clinical implications
to CRT recipients.
PMID- 28401861
TI - Does difference in ICD indication result in a difference in inappropriate shock
risk?
PMID- 28401862
TI - Intra-procedural anticoagulation protocols for left-sided cardiac ablations:
Striking a balance between risk and benefit.
PMID- 28401863
TI - Real-life experience with a new anticoagulation regimen for patients undergoing
left-sided ablation procedures.
AB - BACKGROUND: Current guidelines for anticoagulation during left-sided procedures
recommend the administration of unfractionated heparin (UFH) with an initial
bolus of 50-100 U/kg, followed by continuous infusion to maintain an activated
clotting time (ACT) >= 300 s. Our objective was to compare the effectiveness of
this standard regimen (100 U/kg bolus) to a more aggressive approach (200 U/kg
bolus). METHODS: We collected data on a series of consecutive patients undergoing
left sided ablation procedures. Patients with an INR >=2.0 on the day of the
procedure were excluded. Procedural anticoagulation was performed using one of
two UFH regimens: 1) 100 U/kg bolus, followed by 10 U/kg/hour infusion or 2) 200
U/kg bolus, followed by 20 U/kg/hour infusion. ACT was measured 10 min after the
second bolus and then controlled every 20 min. Heparin was titrated throughout
the procedure to maintain an ACT 300-400 s. RESULTS: 145 consecutive patients
were included in the study: 34 received an initial bolus of 100 U/kg and 111
received 200 U/kg. The mean time required to reach an ACT >=300 s was 15.25 min
(95% CI 12.97-17.03) in the 200 U/kg group and 51.23 min (95% CI 40.65-61.81) in
the 100 U/kg group (p < 0.001). There was no difference between groups with
regard to thromboembolic or hemorrhagic complications. CONCLUSION: Current
anticoagulation guidelines for left-sided ablation procedures almost universally
fail to achieve an initial ACT >=300 s. A 200 U/kg heparin bolus is much more
effective to promptly reach the target ACT, with a low rate of overshoot.
PMID- 28401864
TI - Mitral valve surgery: Does it really decrease ventricular arrhythmia in patients
with mitral valve prolapse?
PMID- 28401866
TI - Perspectives in managing recalls of cardiac implantable electronic devices.
PMID- 28401865
TI - The effect of mitral valve surgery on ventricular arrhythmia in patients with
bileaflet mitral valve prolapse.
AB - BACKGROUND: Bileaflet mitral valve prolapse (biMVP) is associated with frequent
ventricular ectopy (VE) and malignant ventricular arrhythmia. We examined the
effect of mitral valve (MV) surgery on VE burden in biMVP patients. METHODS: We
included 32 consecutive patients undergoing MV surgery for mitral regurgitation
secondary to biMVP between 1993 and 2012 at Mayo Clinic who had available pre-
and post-operative Holter monitoring data. Characteristics of patients with a
significant reduction in postoperative VE (group A, defined as >10% reduction in
VE burden compared to baseline) were compared with the rest of study patients
(group B). RESULTS: In the overall cohort, VE burden was unchanged after the
surgery (41 interquartile range [16, 196] pre-surgery vs. 40 interquartile range
[5186] beats/hour [bph] post-surgery; P = 0.34). However, in 17 patients (53.1%),
VE burden decreased by at least 10% after the surgery. These patients (group A)
were younger than the group B (59 +/- 15 vs. 68 +/- 7 years; P = 0.04). Other
characteristics including pre- and postoperative left ventricular function and
size were similar in both groups. Age <60 years was associated with a reduction
in postoperative VE (odds ratio 5.8; 95% confidence interval, 1.1-44.7; P =
0.03). Furthermore, there was a graded relationship between age and odds of VE
reduction with surgery (odds ratio 1.9; 95% confidence interval 1.04-4.3 per 10
year; P = 0.04). CONCLUSIONS: MV surgery does not uniformly reduce VE burden in
patients with biMVP. However, those patients who do have a reduction in VE burden
are younger, perhaps suggesting that early surgical intervention could modify the
underlying electrophysiologic substrate.
PMID- 28401867
TI - Premature battery depletion with St. Jude Medical ICD and CRT-D devices. Indian
Heart Rhythm Society guidelines for physicians.
PMID- 28401868
TI - Venoplasty of a chronic venous occlusion allowing for cardiac device lead
placement: A team approach.
AB - In patients with complete venous occlusion requiring venous access for cardiac
device lead placement, venous revascularization is a viable option. A
percutaneous approach to venous revascularization has gained popularity. This
method reduces patient exposure to more invasive therapies. In this case series,
we describe two cases of a total venous occlusion that were successfully
revascularized using a "wire externalization" technique. This technique requires
the use of antegrade and retrograde access.
PMID- 28401869
TI - Leadless pacemaker implantation in a patient with complex congenital heart
disease and limited vascular access.
AB - Management of rhythm related issues might be particularly challenging in patients
with congenital heart disease due to complex anatomy and restricted vascular
access. The leadless technology appears a suitable and attractive alternative for
this population. We describe a patient with single ventricle physiology who
successfully underwent implantation of a leadless pacemaker.
PMID- 28401871
TI - [Multidisciplinary approach to the diagnosis of lung cancer at Landspitali
[Editorial]].
PMID- 28401870
TI - Response of narrow QRS tachycardia to premature atrial extra. What is the
mechanism?
AB - A 60-year-old woman was referred for radiofrequency catheter ablation of narrow
QRS tachycardia that was terminated with intravenous adenosine. Twelve-lead ECG
showed no baseline preexcitation. Echocardiogram was essentially normal. The
electrophysiological study showed a normal AH interval of 114 ms and HV interval
of 48 ms during sinus rhythm. Anterograde study demonstrated no dual AV nodal
physiology. Atrial pacing protocols easily and reproducibly induced narrow QRS
tachycardia (Fig. 1A & 1B). Premature atrial extra (PAE) stimuli were delivered
during the tachycardia (Fig. 2). What is the mechanism of the tachycardia?
PMID- 28401872
TI - [Doctoral studies at the Faculty of Medicine, University of Iceland[Editorial]].
PMID- 28401874
TI - [Gallbladder carcinoma in Iceland 2004-2013].
AB - INTRODUCTION: Gallbladder carcinoma is about 0.5% of all cancer. The outcome of
patients with gallbladder carcinoma is overall bad and the only potentially
curative treatment is surgery. The aim of this study was to determine the
disease's prevalence in Iceland and outcome of the patients diagnosed in the
study period. PATIENTS AND METHODS: This was a retrospective study of all
diagnosed patients with gallbladder carcinoma during the years 2004-2013. A list
of patients was obtained from the Icelandic Cancer Registry. Information was
gathered from the patient's charts in Landspitali University Hospital and the
Hospital in Akureyri. Descriptive statistics was used to analyze the results.
Median follow-up time was 6 years. RESULTS: Twenty-four patients were diagnosed
with gallbladder carci-noma in Iceland during the study period, 16 women and 8
men. Eighteen patients were diagnosed in Landspitali and six in the Hospital in
Akureyri. The average age at diagnosis was 73 years. Eighteen patients have died,
on average 5 months after the time of diagnosis. Adenocarcinoma was the most
common cancer type (n=19). Three patients (3/24, 12.5%) underwent extended
operation following the diagnosis of the gallbladder carcinoma. Nine patients
(9/24, 37.5%) had advanced disease at the time of diagnosis and died within two
months after being diagnosed with gallbladder carcinoma. CONCLUSION: Gallbladder
carcinoma is a rare cancer type in Iceland and has a bad prognosis. One third of
the patients had no connection with Landspitali University Hospital following the
diagnosis. Extended surgery following the diagnosis was seldom performed. Key
words: gallbladder carcinoma, gastrointestinal cancer, adenocarcinoma, extended
cholecystectomy. Correspondence: Kristin Huld Haraldsdottir,
kristinh@landspitali.is.
PMID- 28401875
TI - [Tumors of unknown origin: Case report].
AB - IgG4 related disease is a recently recognized chronic fibrotic, inflammatory
condition, caused by infiltrating IgG4 positive plasma cells that can cause tumor
like disease in almost any organ in the body. Typical histopathology is
lymphoplasmocytic infiltration of IgG4 positive cells, storiform fibrosis and
obliterative phlebitis. Glucocorticoids alone or in combination with B-cell
depletion with rituximab causes often good, lasting response. We present here a
lady with recurrent lung infiltration that simulated pneumonia and later tumor of
the lung. She was also earlier diagnosed with lump in the breast that was found
to contain similar IgG4 positive plasma cells that was also demonstrated in the
lung biopsy. She responded very well to rituximab given on 2 occasions. Three
years after this treatment she is in total remission. Key words: IgG4 related
disease, rituximab treatment, plasmacytoma of breast, tumor of lung
Correspondence: Arni Jon Geirsson, arnijon@landspitali.is.
PMID- 28401873
TI - [Fast diagnostic track for suspected lung cancer: A patient centered approach].
AB - INTRODUCTION: The aim of this study is to describe the characteristics of
patients who underwent a fast diagnostic track (FDT) due to suspected lung cancer
at Landspitali University Hospital, Iceland. MATERIAL AND METHODS: Hospital
records were reviewed on background characteristics, diagnosis, staging, waiting
times and survival of all 550 patients (mean age 68.1 years, 57% female) that
participated in the FDT from February 1, 2008 to January 31, 2015. Adjusting for
clinical characteristics in a multivariate analysis, overall survival was
compared for patients diagnosed with lung cancer within or outside the FDT in
Iceland in 2014 (n=167, mean age 69.3 years, 61.7% female). RESULTS: Of the 550
FDT patients, 426 were diagnosed with lung cancer (77.5%); 346 of the non-small
cell type (NSCLC) (81.2%). The proportion of patients receiving lung cancer
diagnosis through the FDT increased from 23.3% in 2008 to 47.9% in 2014
(p<0.001). The waiting time from referral to diagnosis was 10 days median and 19
days from diagnosis to initiation of treatment. More patients with advanced
disease were diagnosed outside the FDT (70.1% vs. 37.5%, p<0.05). When ad--
justed for age, sex, histology, stage at diagnosis and therapy, patients
diagnosed with lung cancer outside the FDT had higher risk of all-cause mortality
(HR 1.60; 95% CI: 0.95 - 2.71) although the difference was not statistically
significant. CONCLUSION: An increasing proportion of lung cancer diagnosis in
Iceland is made through a fast diagnostic track with potential benefits for
patients. The waiting time from referral to diagnosis and treatment is in line
with international guidelines. Key words: lung cancer, non-small cell lung
cancer, diagnostic track, waiting times, survival. Correspondence: Hronn
Hardardottir, hronnh@landspitali.is.
PMID- 28401877
TI - Non-close-packed three-dimensional quasicrystals.
AB - Quasicrystals are frequently encountered in condensed matter. They are important
candidates for equilibrium phases from the atomic scale to the nanoscale. Here,
we investigate the computational self-assembly of four quasicrystals in a single
model system of identical particles interacting with a tunable isotropic pair
potential. We reproduce a known icosahedral quasicrystal and report a decagonal
quasicrystal, a dodecagonal quasicrystal, and an octagonal quasicrystal. The
quasicrystals have low coordination number or occur in systems with mesoscale
density variations. We also report a network gel phase.
PMID- 28401876
TI - Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed
patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase
IIIb study.
AB - BACKGROUND: Simplified dosing regimens are important for patients who face
challenges in adhering to HIV-1 therapy. We investigated the safety and
virological efficacy of switching to once-daily abacavir/dolutegravir/lamivudine
(ABC/DTG/3TC). METHODS: The STRIIVING study was a randomized, open-label, Phase
IIIb study in adults with HIV-1 RNA <50 copies/ml on antiretroviral therapy (ART)
at enrolment (ClinicalTrials.gov identifier, NCT02105987). Subjects were randomly
assigned to switch to ABC/DTG/3TC once daily for 48 weeks (early-switch group) or
continue current ART for 24 weeks and then switch to ABC/DTG/3TC (late-switch
group). The primary end point was the proportion of subjects with HIV-1 RNA <50
copies/ml at week 24. RESULTS: Of 553 subjects enrolled, 275 were randomly
assigned to switch immediately to ABC/DTG/3TC and 278 continued on current ART.
At week 24, 85% and 88% of subjects who switched to ABC/DTG/3TC or remained on
current ART, respectively, were virologically suppressed, indicating that
ABC/DTG/3TC was non-inferior (difference in proportion, -3.4%; 95% CI -9.1, 2.4).
At week 48, 83% and 92% were virologically suppressed in the early- and late
switch groups, respectively. Adverse events were reported more frequently with
ABC/DTG/3TC (66%) than with current ART (47%) by week 24, and in the late-switch
group, 60% of subjects reported adverse events post-switch. Pharmacokinetic data
supported immediate switch. HIV Treatment Satisfaction Questionnaire scores
improved in participants switching to ABC/DTG/3TC versus current ART.
CONCLUSIONS: Data demonstrating non-inferiority of switching to ABC/DTG/3TC
versus continuing current ART support ABC/DTG/3TC as an option when considering
switch regimens in HIV-1-infected adults with stable viral suppression.
PMID- 28401878
TI - Negative and positive cross-correlations of current noises in quantum Hall edge
channels at bulk filling factor [Formula: see text].
AB - Cross-correlation noise in electrical currents generated from a series connection
of two quantum point contacts (QPCs), the injector and the detector, is described
for investigating energy relaxation in quantum Hall edge channels at bulk filling
factor [Formula: see text]. We address the importance of tuning the energy bias
across the detector for this purpose. For a long channel with a macroscopic
floating ohmic contact that thermalizes the electrons, the cross-correlation
turns from negative values to the maximally positive value (identical noise in
the two currents) by tuning the effective energy bias to zero. This can be
understood by considering competition between the low-frequency charge
fluctuation generated at the injector, which contributes positive correlation,
and the partition noise at the detector, which gives negative correlation.
Strikingly, even for a short channel without intentional thermalization,
significantly large positive correlation is observed in contrast to negative
values expected for coherent transport between the two QPCs.
PMID- 28401879
TI - Left colon obstruction due to non-reducible Spigelian hernia of the right side.
Report of a case and literature review.
AB - AIM: Describe a rare case of intestinal obstruction due to sigmoid colon
incarceration into a right Spigelian hernia and provide a literature review about
its surgical management. MATERIAL OF STUDY: An 88 year-old man presented with a 3
day history of right lower quadrant pain and abdominal distension. Clinical
examination revealed a not reducible palpable mass on right side of the anterior
abdominal wall. Computed tomography shown signs of intestinal obstruction and a
Spigelian hernia of about 3 cm. RESULTS: Sigmoid colon was incarcerated in the
defect but no signs of intestinal ischemia was found during the surgical
exploration. The hernia content was reduced and the defect was repaired with a
polypropylene mesh placed in the pre-peritoneal space. Postoperative period was
uneventful and the patient was discharged on the fourth postoperative day.
DISCUSSION: Spigelian hernia occurs through congenital or acquired defects in the
Spigelian fascia at the level of the semicircular line. Clinical presentation
depends on the size and the pattern of the hernia defect. In some cases, symptoms
are no specific and uncommon findings have been reported so far. Preoperative
establishment of the hernia content and the location of the sac is mandatory to
plan a correct surgical strategy. Intestinal incarceration often occurs and
suggests a prompt surgical exploration. CONCLUSIONS: Colonic obstruction
secondary to an incarcerated Spigelian hernia is a rare but dangerous occurrence.
Surgical approach is selected based on patient's conditions and surgeon's
expertise. In a non-contaminated surgical field, the use of prosthesis is
recommended. KEY WORDS: Intestinal obstruction, Mesh repair, Spigelian hernia.
PMID- 28401880
TI - Gallstone ileus. A case treated with minilaparotomy and a review of the
literature.
AB - : Gallstone ileus is a rare complication of cholelithiasis which occurs in less
than 1% of patients and is the cause of 1- 4% of cases of small bowel
obstruction. The pathogenesis involves the formation of a bilioenteric fistula.
We report the case of gallstone ileus in an 81-year old woman with typical
abdominal pain, arterial hypertension and coronary artery disease. An abdominal
computed tomography (CT) scan showed pneumobilia, dilated loops of small bowel
and an ectopic gallstone obstructing the intestinal lumen. The patient underwent
enterolithotomy and a 5-cm stone 20 cm from the ileocecal valve was removed. In
the literature enterolithotomy alone is the procedure most frequently used for
gallstone ileus. Enterolithotomy plus cholecystectomy and/or fistulectomy is only
indicated in selected patients. The clinical signs and symptoms depend on the
site of the obstruction and usually include abdominal pain, nausea and vomiting.
The diagnostic test of choice is an abdominal CT scan. KEY WORDS:
Cholecystoenteric fistula, Gallstone ileus, Minilaparotomy.
PMID- 28401881
TI - Classical synchronization indicates persistent entanglement in isolated quantum
systems.
AB - Synchronization and entanglement constitute fundamental collective phenomena in
multi-unit classical and quantum systems, respectively, both equally implying
coordinated system states. Here, we present a direct link for a class of isolated
quantum many-body systems, demonstrating that synchronization emerges as an
intrinsic system feature. Intriguingly, quantum coherence and entanglement arise
persistently through the same transition as synchronization. This direct link
between classical and quantum cooperative phenomena may further our understanding
of strongly correlated quantum systems and can be readily observed in state-of
the-art experiments, for example, with ultracold atoms.
PMID- 28401882
TI - Multiscale structural and electronic control of molybdenum disulfide foam for
highly efficient hydrogen production.
AB - Hydrogen production through water splitting has been considered as a green, pure
and high-efficient technique. As an important half-reaction involved, hydrogen
evolution reaction is a complex electrochemical process involving liquid-solid
gas three-phase interface behaviour. Therefore, new concepts and strategies of
material design are needed to smooth each pivotal step. Here we report a
multiscale structural and electronic control of molybdenum disulfide foam to
synergistically promote the hydrogen evolution process. The optimized three
dimensional molybdenum disulfide foam with uniform mesopores, vertically aligned
two-dimensional layers and cobalt atoms doping demonstrated a high hydrogen
evolution activity and stability. In addition, density functional theory
calculations indicate that molybdenum disulfide with moderate cobalt doping
content possesses the optimal activity. This study demonstrates the validity of
multiscale control in molybdenum disulfide via overall consideration of the mass
transport, and the accessibility, quantity and capability of active sites towards
electrocatalytic hydrogen evolution, which may also be extended to other energy
related processes.
PMID- 28401883
TI - Cognate antigen engagement on parenchymal cells stimulates CD8+ T cell
proliferation in situ.
AB - T-cell responses are initiated upon cognate presentation by professional antigen
presenting cells in lymphoid tissue. T cells then migrate to inflamed tissues,
but further T-cell stimulation in these parenchymal target sites is not well
understood. Here we show that T-cell expansion within inflamed tissues is a
distinct phase that is neither a classical primary nor classical secondary
response. This response, which we term 'the mezzanine response', commences within
days after initial antigen encounter, unlike the secondary response that usually
occurs weeks after priming. A further distinction of this response is that T-cell
proliferation is driven by parenchymal cell antigen presentation, without
requiring professional antigen presenting cells, but with increased dependence on
IL-2. The mezzanine response might, therefore, be a new target for inhibiting T
cell responses in allograft rejection and autoimmunity or for enhancing T-cell
responses in the context of microbial or tumour immunity.
PMID- 28401885
TI - Corrigendum: Fluorescence-tunable Ag-DNA biosensor with tailored cytotoxicity for
live-cell applications.
PMID- 28401884
TI - Anisotropic forces from spatially constrained focal adhesions mediate contact
guidance directed cell migration.
AB - Directed migration by contact guidance is a poorly understood yet vital
phenomenon, particularly for carcinoma cell invasion on aligned collagen fibres.
We demonstrate that for single cells, aligned architectures providing contact
guidance cues induce constrained focal adhesion maturation and associated F-actin
alignment, consequently orchestrating anisotropic traction stresses that drive
cell orientation and directional migration. Consistent with this understanding,
relaxing spatial constraints to adhesion maturation either through reduction in
substrate alignment density or reduction in adhesion size diminishes the contact
guidance response. While such interactions allow single mesenchymal-like cells to
spontaneously 'sense' and follow topographic alignment, intercellular
interactions within epithelial clusters temper anisotropic cell-substratum
forces, resulting in substantially lower directional response. Overall, these
results point to the control of contact guidance by a balance of cell-substratum
and cell-cell interactions, modulated by cell phenotype-specific cytoskeletal
arrangements. Thus, our findings elucidate how phenotypically diverse cells
perceive ECM alignment at the molecular level.
PMID- 28401886
TI - On the discrepancy between observed and CMIP5 multi-model simulated Barents Sea
winter sea ice decline.
AB - This study aims to understand the relative roles of external forcing versus
internal climate variability in causing the observed Barents Sea winter sea ice
extent (SIE) decline since 1979. We identify major discrepancies in the spatial
patterns of winter Northern Hemisphere sea ice concentration trends over the
satellite period between observations and CMIP5 multi-model mean externally
forced response. The CMIP5 externally forced decline in Barents Sea winter SIE is
much weaker than that observed. Across CMIP5 ensemble members, March Barents Sea
SIE trends have little correlation with global mean surface air temperature
trends, but are strongly anti-correlated with trends in Atlantic heat transport
across the Barents Sea Opening (BSO). Further comparison with control simulations
from coupled climate models suggests that enhanced Atlantic heat transport across
the BSO associated with regional internal variability may have played a leading
role in the observed decline in winter Barents Sea SIE since 1979.
PMID- 28401887
TI - Bone marrow mesenchymal stem cells combine with Treated dentin matrix to build
biological root.
AB - Treated dentin matrix (TDM) as a kind of scaffolding material has been proved
odontogenic induction ability on dental-derived stem cells. Given the limited
resources of dental stem cells, it is necessary to seek new seed cell which
easily obtained. Jaw bone marrow mesenchymal stem cell (JBMMSC) as non-dental
derived stem cell relates to the development of teeth and jaws which suggest us
JBMMSCs could act as a new seed cell for tooth tissue engineering. To assess the
odontogenic and osteogenic potential of JBMMSCs, cells were induced by TDM
extraction in vitro and combined with TDM in vivo. Results were analyzed by PCR,
Western Blotting and histology. PCR and Western Blotting showed odontogenic and
osteogenic makers were significantly enhanced in varying degrees after induced by
TDM extraction in vitro. In vivo, JBMMSCs expressed both odontogenic and
osteogenic-related protein, and the latter showed stronger positive expression.
Furthermore, histological examination of the harvested grafts was observed the
formation of bone-like tissue. Therefore, osteogenic differentiation ability of
JBMMSCs were enhanced significantly after being inducted by TDM which illustrates
that non-odontogenic derived stem cells are still promising seed cells in tooth
root tissue engineering.
PMID- 28401889
TI - Proper time regularization and the QCD chiral phase transition.
AB - We study the QCD chiral phase transition at finite temperature and finite quark
chemical potential within the two flavor Nambu-Jona-Lasinio (NJL) model, where a
generalization of the proper-time regularization scheme is motivated and
implemented. We find that in the chiral limit the whole transition line in the
phase diagram is of second order, whereas for finite quark masses a crossover is
observed. Moreover, if we take into account the influence of quark condensate to
the coupling strength (which also provides a possible way of how the effective
coupling varies with temperature and quark chemical potential), it is found that
a CEP may appear. These findings differ substantially from other NJL results
which use alternative regularization schemes, some explanation and discussion are
given at the end. This indicates that the regularization scheme can have a
dramatic impact on the study of the QCD phase transition within the NJL model.
PMID- 28401888
TI - Advances in pancreatic islet monolayer culture on glass surfaces enable super
resolution microscopy and insights into beta cell ciliogenesis and proliferation.
AB - A robust and reproducible method for culturing monolayers of adherent and well
spread primary islet cells on glass coverslips is required for detailed imaging
studies by super-resolution and live-cell microscopy. Guided by an observation
that dispersed islet cells spread and adhere well on glass surfaces in neuronal
co-culture and form a monolayer of connected cells, we demonstrate that in the
absence of neurons, well-defined surface coatings combined with components of
neuronal culture media collectively support robust attachment and growth of
primary human or rat islet cells as monolayers on glass surfaces. The islet cell
monolayer cultures on glass stably maintain distinct mono-hormonal insulin+,
glucagon+, somatostatin+ and PP+ cells and glucose-responsive synchronized
calcium signaling as well as expression of the transcription factors Pdx-1 and
NKX-6.1 in beta cells. This technical advance enabled detailed observation of sub
cellular processes in primary human and rat beta cells by super-resolution
microscopy. The protocol is envisaged to have broad applicability to
sophisticated analyses of pancreatic islet cells that reveal new biological
insights, as demonstrated by the identification of an in vitro protocol that
markedly increases proliferation of primary beta cells and is associated with a
reduction in ciliated, ostensibly proliferation-suppressed beta cells.
PMID- 28401890
TI - Ultra-high open-circuit voltage of perovskite solar cells induced by nucleation
thermodynamics on rough substrates.
AB - To obtain high performance CH3NH3PbI3 perovskite solar cells, it is highly
important to realise a high open-circuit voltage. Calculation results based on a
modified diode model have indicated that a low bare ratio phi of the perovskite
film is the most important factor determining the open-circuit voltage, where phi
is defined as the ratio of the projection of the uncovered area of the perovskite
film to the apparent area of the total substrate surface. To realise a low phi,
we investigate the nucleation behaviour of crystals on rough substrates. The
analysis results predict that, when CH3NH3PbI3 is deposited on conventional
transparent conductive oxide substrates such as fluorine-doped tin oxide,
preferential heterogeneous nucleation will occur on the concave regions of the
substrate; then, depending on the subsequent growth step, full coverage of the
perovskite film at both the macroscopic and microscopic scales is realised. As a
result, an ultra-high open-circuit voltage, i.e., 1.20 V, can be achieved in
devices using the full coverage CH3NH3PbI3 film. The thermodynamics theory of
precipitation nucleation should shed light on solution engineering of thin films.
PMID- 28401891
TI - Genome assembly with in vitro proximity ligation data and whole-genome
triplication in lettuce.
AB - Lettuce (Lactuca sativa) is a major crop and a member of the large, highly
successful Compositae family of flowering plants. Here we present a reference
assembly for the species and family. This was generated using whole-genome
shotgun Illumina reads plus in vitro proximity ligation data to create large
superscaffolds; it was validated genetically and superscaffolds were oriented in
genetic bins ordered along nine chromosomal pseudomolecules. We identify several
genomic features that may have contributed to the success of the family,
including genes encoding Cycloidea-like transcription factors, kinases, enzymes
involved in rubber biosynthesis and disease resistance proteins that are expanded
in the genome. We characterize 21 novel microRNAs, one of which may trigger
phasiRNAs from numerous kinase transcripts. We provide evidence for a whole
genome triplication event specific but basal to the Compositae. We detect 26% of
the genome in triplicated regions containing 30% of all genes that are enriched
for regulatory sequences and depleted for genes involved in defence.
PMID- 28401892
TI - Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to
synergistically activate Cdx2 during specification of the trophectoderm.
AB - The first binary cell fate decision occurs at the morula stage and gives rise to
two distinct types of cells that constitute the trophectoderm (TE) and inner cell
mass (ICM). The cell fate determinant, Cdx2, is induced in TE cells and plays an
essential role in their differentiation and maintenance. Notch and Hippo
signaling cascades are assumed to converge onto regulatory elements of Cdx2,
however, the underlying molecular mechanisms are largely unknown. Here, we show
involvement of Strawberry Notch1 (Sbno1), a novel chromatin factor of the
helicase superfamily 2, during preimplantation development. Sbno1 knockout
embryos die at the preimplantation stage without forming a blastocoel, and Cdx2
is not turned on even though both Yap and Tead4 reside normally in nuclei.
Accordingly, Sbno1 acts on the trophectoderm-enhancer (TEE) of Cdx2, ensuring its
robust and synergistic activation by the Yap/Tead4 and NICD/Rbpj complexes.
Interestingly, this synergism is enhanced when cells are mechanically stretched,
which might reflect that TE cells are continuously stretched by the expanding ICM
and blastocoel cavity. In addition, the histone chaperone, FACT (FAcilitates
Chromatin Transcription) physically interacts with Sbno1. Our data provide new
evidence on TE specification, highlighting unexpected but essential functions of
the highly conserved chromatin factor, Sbno1.
PMID- 28401894
TI - Luminescent manganese-doped CsPbCl3 perovskite quantum dots.
AB - Nanocrystalline cesium lead halide perovskites (CsPbX3, X = Cl, Br, and I) form
an exciting new class of semiconductor materials showing quantum confinement. The
emission color can be tuned over the full visible spectral region making them
promising for light-emitting applications. Further control over the optical and
magnetic properties of quantum dots (QDs) can be achieved through doping of
transition metal (TM) ions such as Mn2+ or Co2+. Here we demonstrate how,
following QD synthesis in the presence of a Mn-precursor, dropwise addition of
silicon tetrachloride (SiCl4) to the QDs in toluene results in the formation of
Mn-doped CsPbCl3 QDs showing bright orange Mn2+ emission around 600 nm. Evidence
for successful doping is provided by excitation spectra of the Mn2+ emission,
with all features of the CsPbCl3 QD absorption spectrum and a decrease of the 410
nm excitonic emission life time with increasing Mn-concentration, giving evidence
for enhanced exciton to Mn2+ energy transfer. As a doping mechanism we propose a
combination of surface etching and reconstruction and diffusion doping. The
presently reported approach provides a promising avenue for doping TM ions into
perovskites QDs enabling a wider control over optical and magnetic properties for
this new class of QDs.
PMID- 28401893
TI - Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of
Clonal Group ST131 in Animal Models of Bacteremia.
AB - Multi-drug resistant (MDR) enteric bacteria are of increasing global concern. A
clonal group, Escherichia coli sequence type (ST) 131, harbors both MDR and a
deadly complement of virulence factors. Patients with an immunocompromised system
are at high risk of infections with these E. coli and there is strong
epidemiologic evidence that the human intestinal tract, as well as household
pets, may be a reservoir. Here, we examine if phages are an effective treatment
strategy against this clonal group in murine models of bacteremia that
recapitulate clinical infections. Bacteriophages isolated from known E. coli
reservoirs lyse a diverse array of MDR ST131 clinical isolates. Phage HP3 reduced
E. coli levels and improved health scores for mice infected with two distinct
ST131 strains. Efficacy was correlated to in vitro lysis ability by the infecting
phage and the level of virulence of the E. coli strain. Importantly, it is also
demonstrated that E. coli bacteremia initiated from translocation across the
intestinal tract in an immunocompromised host is substantially reduced after
phage treatment. This study demonstrates that phage, isolated from the
environment and with little experimental manipulation, can be effective in
combating even the most serious of infections by E. coli "superbugs".
PMID- 28401895
TI - Integrated host and viral transcriptome analyses reveal pathology and
inflammatory response mechanisms to ALV-J injection in SPF chickens.
AB - Avian leukosis virus (ALV) is detrimental to poultry health and causes
substantial economic losses from mortality and decreased performance. Because
tumorigenesis is a complex mechanism, the regulatory architecture of the immune
system is likely to include the added dimensions of modulation by miRNAs and long
noncoding RNA (lncRNA). To characterize the response to ALV challenge, we
developed a novel methodology that combines four datasets: mRNA expression and
the associated regulatory factors of miRNA and lncRNA, and ALV gene expression.
Specific Pathogen-Free (SPF) layer chickens were infected with ALV-J or
maintained as non-injected controls. Spleen samples were collected at 40 days
post injection (dpi), and sequenced. There were 864 genes, 7 miRNAs and 17
lncRNAs differentially expressed between infected and non-infected birds. The
combined analysis of the 4 RNA expression datasets revealed that ALV infection is
detected by pattern-recognition receptors (TLR9 and TLR3) leading to a type-I IFN
mediated innate immune response that is modulated by IRF7 and IRF1. Co-expression
network analysis of mRNA with miRNA, lncRNA and virus genes identified key
elements within the complex networks utilized during ALV response. The
integration of information from the host transcriptomic, epigenetic and virus
response also has the potential to provide deeper insights into other host
pathogen interactions.
PMID- 28401896
TI - Lead exposure, IgE, and the risk of asthma in children.
AB - Lead (Pb) has adverse effects on our nervous system and renal systems. Young
children are more vulnerable to Pb exposure. However, the role of low-level Pb
exposure in the immune system and allergic diseases in children is not well
established. The aims of this study are to investigate the associations between
Pb exposure and allergic diseases; between Pb and immunoglobulin E (IgE) as an
intervening variable; and gender-based differences. We used multistage stratified
random sampling to recruit kindergarten children nationwide in Taiwan.
Information about allergic diseases and environmental exposures was collected by
questionnaire. We compared children with and without allergic diseases for blood
Pb levels measured by inductively coupled plasma mass spectrometry. The
association between blood Pb and allergic diseases was assessed by logistic
regression and those between Pb and IgE by generalized linear models. We also
conducted mediation analysis to evaluate how much risk of allergic diseases
related to Pb exposure is explained by IgE. A total of 930 children completed
specimen collections. There was a positive association between Pb and asthma.
Blood Pb were also positively linked with serum IgE (beta=0.26 kU/l per ln-unit
increase Pb concentration; 95% CI 0.009-0.50 kU/l), after adjusting for potential
confounders. Analyses stratified by gender revealed that blood Pb correlated with
IgE only in boys (beta=0.40 kU/l; 95% CI 0.03-0.76 kU/l). We estimated that 38%
of the total effect of Pb exposure on asthma is mediated by IgE levels. In
conclusion, Pb exposure is associated with both blood IgE and asthma in boys.
Moreover, the effect of Pb exposure on asthma may be mediated by IgE levels.
PMID- 28401897
TI - Label-free volumetric optical imaging of intact murine brains.
AB - A central effort of today's neuroscience is to study the brain's 'wiring
diagram'. The nervous system is believed to be a network of neurons interacting
with each other through synaptic connection between axons and dendrites,
therefore the neuronal connectivity map not only depicts the underlying anatomy,
but also has important behavioral implications. Different approaches have been
utilized to decipher neuronal circuits, including electron microscopy (EM) and
light microscopy (LM). However, these approaches typically demand extensive
sectioning and reconstruction for a brain sample. Recently, tissue clearing
methods have enabled the investigation of a fully assembled biological system
with greatly improved light penetration. Yet, most of these implementations,
still require either genetic or exogenous contrast labeling for light microscopy.
Here we demonstrate a high-speed approach, termed as Clearing Assisted Scattering
Tomography (CAST), where intact brains can be imaged at optical resolution
without labeling by leveraging tissue clearing and the scattering contrast of
optical frequency domain imaging (OFDI).
PMID- 28401898
TI - A unique haplotype of RCCX copy number variation: from the clinics of congenital
adrenal hyperplasia to evolutionary genetics.
AB - There is a difficulty in the molecular diagnosis of congenital adrenal
hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898)
variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic
and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX
copy number variation (CNV) structures, which harbor CYP21A2, was performed. In
total, 389 unrelated Hungarian individuals with European ancestry (164 healthy
subjects, 125 patients with non-functioning adrenal incidentaloma and 100
patients with classical CAH) as well as 34 adrenocortical tumor specimens were
studied using a set of experimental and bioinformatic methods. A unique,
moderately frequent (2%) haplotypic RCCX CNV structure with three repeated
segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in
the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472)
variant in the middle segment occurred in all c.955C>T carriers with normal
steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced
mRNA in the adrenal gland, confirming its functionality and ability to rescue the
carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH
patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived
from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the
middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish
between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in
the studied European population. Therefore, c.*12C>T may be suitable as a marker
to avoid this genetic confound and improve the diagnosis of CAH.
PMID- 28401899
TI - Improved imputation accuracy of rare and low-frequency variants using population
specific high-coverage WGS-based imputation reference panel.
AB - Genetic imputation is a cost-efficient way to improve the power and resolution of
genome-wide association (GWA) studies. Current publicly accessible imputation
reference panels accurately predict genotypes for common variants with minor
allele frequency (MAF)>=5% and low-frequency variants (0.5<=MAF<5%) across
diverse populations, but the imputation of rare variation (MAF<0.5%) is still
rather limited. In the current study, we evaluate imputation accuracy achieved
with reference panels from diverse populations with a population-specific high
coverage (30 *) whole-genome sequencing (WGS) based reference panel, comprising
of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian
specific panel contains fewer haplotypes and variants, the imputation confidence
and accuracy of imputed low-frequency and rare variants was significantly higher.
The results indicate the utility of population-specific reference panels for
human genetic studies.
PMID- 28401900
TI - An efficient and flexible test for rare variant effects.
AB - Since it has been claimed that rare variants with extremely small allele
frequency play a crucial role in complex traits, there is great demand for the
development of a powerful test for detecting these variants. However, due to the
extremely low frequencies of rare variants, common statistical testing methods do
not work well, which has motivated recent extensive research on developing an
efficient testing procedure for rare variant effects. Many studies have suggested
effective testing procedures with reasonably high power under some presumed
assumptions of parametric statistical models. However, if the parametric
assumptions are violated, these tests are possibly under-powered. In this paper,
we develop an optimal, powerful statistical test called the aggregated
conditional score test (ACST) for simultaneously testing M rare variant effects
without restrictive parametric assumptions. The proposed test uses a test
statistic aggregating the conditional score statistics of effect sizes of M rare
variants. In simulation studies, ACST generally performed well compared with the
two most commonly used tests, the optimal sequence kernel association test (SKAT
O) and Kullback-Leibler distance test. Finally, we demonstrate the performance
and practical utility of ACST using the Dallas Heart Study data.
PMID- 28401901
TI - Missing heritability: is the gap closing? An analysis of 32 complex traits in the
Lifelines Cohort Study.
AB - Despite the recent explosive rise in number of genetic markers for complex
disease traits identified in genome-wide association studies, there is still a
large gap between the known heritability of these traits and the part explained
by these markers. To gauge whether this 'heritability gap' is closing, we first
identified genome-wide significant SNPs from the literature and performed
replication analyses for 32 highly relevant traits from five broad disease areas
in 13 436 subjects of the Lifelines Cohort. Next, we calculated the variance
explained by multi-SNP genetic risk scores (GRSs) for each trait, and compared it
to their broad- and narrow-sense heritabilities captured by all common SNPs. The
majority of all previously-associated SNPs (median=75%) were significantly
associated with their respective traits. All GRSs were significant, with
unweighted GRSs generally explaining less phenotypic variance than weighted GRSs,
for which the explained variance was highest for height (15.5%) and varied
between 0.02 and 6.7% for the other traits. Broad-sense common-SNP heritability
estimates were significant for all traits, with the additive effect of common
SNPs explaining 48.9% of the variance for height and between 5.6 and 39.2% for
the other traits. Dominance effects were uniformly small (0-1.5%) and not
significant. On average, the variance explained by the weighted GRSs accounted
for only 10.7% of the common-SNP heritability of the 32 traits. These results
indicate that GRSs may not yet be ready for accurate personalized prediction of
complex disease traits limiting widespread adoption in clinical practice.
PMID- 28401902
TI - A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast
Cancer Patients using Quantitative Ultrasound.
AB - Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour
characteristics. Using a 6-MHz ultrasound system, radiofrequency data were
acquired from 56 locally advanced breast cancer patients prior to their
neoadjuvant chemotherapy (NAC) and QUS texture features were computed from
regions of interest in tumour cores and their margins as potential predictive and
prognostic indicators. Breast tumour molecular features were also collected and
used for analysis. A multiparametric QUS model was constructed, which
demonstrated a response prediction accuracy of 88% and ability to predict patient
5-year survival rates (p = 0.01). QUS features demonstrated superior performance
in comparison to molecular markers and the combination of QUS and molecular
markers did not improve response prediction. This study demonstrates, for the
first time, that non-invasive QUS features in the core and margin of breast
tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and
predict five-year recurrence-free survival.
PMID- 28401904
TI - Intercalant-independent transition temperature in superconducting black
phosphorus.
AB - Research on black phosphorus has been experiencing a renaissance over the last
years, after the demonstration that few-layer crystals exhibit high carrier
mobility and a thickness-dependent bandgap. Black phosphorus is also known to be
a superconductor under high pressure exceeding 10 GPa. The superconductivity is
due to a structural transformation into another allotrope and accompanied by a
semiconductor-metal transition. No superconductivity could be achieved for black
phosphorus in its normal orthorhombic form, despite several reported attempts.
Here we describe its intercalation by several alkali metals (Li, K, Rb and Cs)
and alkali-earth Ca. All the intercalated compounds are found to be
superconducting, exhibiting the same (within experimental accuracy) critical
temperature of 3.8+/-0.1 K and practically identical characteristics in the
superconducting state. Such universal superconductivity, independent of the
chemical composition, is highly unusual. We attribute it to intrinsic
superconductivity of heavily doped individual phosphorene layers, while the
intercalated layers of metal atoms play mostly a role of charge reservoirs.
PMID- 28401903
TI - Impact of metric and sample size on determining malaria hotspot boundaries.
AB - The spatial heterogeneity of malaria suggests that interventions may be targeted
for maximum impact. It is unclear to what extent different metrics lead to
consistent delineation of hotspot boundaries. Using data from a large community
based malaria survey in the western Kenyan highlands, we assessed the agreement
between a model-based geostatistical (MBG) approach to detect hotspots using
Plasmodium falciparum parasite prevalence and serological evidence for exposure.
Malaria transmission was widespread and highly heterogeneous with one third of
the total population living in hotspots regardless of metric tested. Moderate
agreement (Kappa = 0.424) was observed between hotspots defined based on parasite
prevalence by polymerase chain reaction (PCR)- and the prevalence of antibodies
to two P. falciparum antigens (MSP-1, AMA-1). While numerous biologically
plausible hotspots were identified, their detection strongly relied on the
proportion of the population sampled. When only 3% of the population was sampled,
no PCR derived hotspots were reliably detected and at least 21% of the population
was needed for reliable results. Similar results were observed for hotspots of
seroprevalence. Hotspot boundaries are driven by the malaria diagnostic and
sample size used to inform the model. These findings warn against the simplistic
use of spatial analysis on available data to target malaria interventions in
areas where hotspot boundaries are uncertain.
PMID- 28401905
TI - apterous Brain Neurons Control Receptivity to Male Courtship in Drosophila
Melanogaster Females.
AB - Courtship behaviours allow animals to interact and display their qualities before
committing to reproduction. In fly courtship, the female decides whether or not
to mate and is thought to display receptivity by slowing down to accept the male.
Very little is known on the neuronal brain circuitry controlling female
receptivity. Here we use genetic manipulation and behavioural studies to identify
a novel set of neurons in the brain that controls sexual receptivity in the
female without triggering the postmating response. We show that these neurons,
defined by the expression of the transcription factor apterous, affect the
modulation of female walking speed during courtship. Interestingly, we found that
the apterous neurons required for female receptivity are neither doublesex nor
fruitless positive suggesting that apterous neurons are not specified by the sex
determination cascade. Overall, these findings identify a neuronal substrate
underlying female response to courtship and highlight the central role of walking
speed in the receptivity behaviour.
PMID- 28401906
TI - Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat:
involvement of alpha-synuclein aggregation and programmed cell death.
AB - Clinical studies report significant increases in acrolein (an alpha,beta
unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's
disease (PD). In the present study, acrolein-induced neurotoxicity in the
nigrostriatal dopaminergic system was investigated by local infusion of acrolein
(15, 50, 150 nmoles/0.5 MUl) in the SN of Sprague-Dawley rats. Acrolein-induced
neurodegeneration of nigrostriatal dopaminergic system was delineated by
reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and
TH-positive neurons in the infused SN as well as in striatal dopamine content. At
the same time, apomorphine-induced turning behavior was evident in rats subjected
to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by
increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein
conjugated with proteins at lysine residue and induced alpha-synuclein
aggregation in the infused SN. Acrolein was pro-inflammatory by activating
astrocytes and microglia. In addition, acrolein activated caspase 1 in the
infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic
mechanisms underlying acrolein-induced neurotoxicity involved programmed cell
death, including apoptosis and necroptosis. Compared with well-known Parkinsonian
neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone
which do not exist in the SN of PD patients, our in vivo study shows that
acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic
system of rat brain.
PMID- 28401907
TI - Protective efficacy of Zika vaccine in AG129 mouse model.
AB - Zika virus (ZIKV) is a mosquito-borne flavivirus that causes asymptomatic
infection or presents only mild symptoms in majority of those infected. However,
vaccination for ZIKV is a public health priority due to serious congenital and
neuropathological abnormalities observed as a sequelae of the virus infection in
the recent epidemics. We have developed an inactivated virus vaccine with the
African MR 766 strain. Here we show that two doses of the vaccine provided 100%
efficacy against mortality and disease following challenge with homotypic MR 766
and the heterotypic FSS 13025 ZIKV strains in the Type I and Type II interferon
deficient AG129 mice. Two doses of the vaccine elicited high titer of
neutralizing antibodies in Balb/c mice, and the vaccine antisera conferred
protection against virus challenge in passively immunized mice. The studies were
useful to rationalize vaccine doses for protective efficacy. Furthermore, the
vaccine antisera neutralized the homotypic and heterotypic ZIKV strains in vitro
with equivalent efficiency. Our study suggests a single ZIKV serotype, and that
the development of an effective vaccine may not be limited by the choice of virus
strain.
PMID- 28401908
TI - Regulation of miR163 and its targets in defense against Pseudomonas syringae in
Arabidopsis thaliana.
AB - Small RNAs are important regulators for a variety of biological processes,
including leaf development, flowering-time, embryogenesis and defense responses.
miR163 is a non-conserved miRNA and its locus has evolved recently through
inverted duplication of its target genes to which they belong to the SABATH
family of related small-molecule methyltransferases (MTs). In Arabidopsis
thaliana, previous study demonstrated that miR163 accumulation was induced by
alamethicin treatment, suggesting its roles in defense response pathways.
Enhanced resistance against Pseudomonas syringae pv. tomato (Pst) was observed in
the mir163 mutant, whereas transgenic lines overexpressing miR163 showed increase
sensitivity to Pst, suggesting that miR163 is a negative regulator of defense
response. Elevated level of miR163 and its targets in A. thaliana were observed
upon Pst treatment, suggesting a modulating relationship between miR163 and its
targets. In addition, miR163 and histone deacetylase were found to act
cooperatively in mediating defense against Pst. Transgenic plants overexpressing
miR163-resistant targets suggested their different contributions in defense.
Results from this study revealed that the stress-inducible miR163 and its targets
act in concert to modulate defense responses against bacterial pathogen in A.
thaliana.
PMID- 28401909
TI - An Intrathermocline Eddy and a tropical cyclone in the Bay of Bengal.
AB - The Bay of Bengal, subjected to monsoonal forcing and tropical cyclones, displays
a complex field of ocean eddies. On 5 December 2013 a sub-surface vortex or
Intrathermocline Eddy (ITE) composed of water characteristic of the Andaman Sea
was observed within the thermocline of the western Bay of Bengal. We propose that
the ITE was the product of Tropical Cyclone Lehar interaction on 27 November 2013
with a westward propagating surface eddy from the eastern Bay of Bengal. While
Lehar's interaction with the ocean initially removes heat from the upper layers
of the eddy, air-sea flux is limited as the deeper portions of the eddy was
subducted into the stratified thermocline, inhibiting further interaction with
the atmosphere. The ITE core from 30 to 150 m is thus isolated from local air-sea
fluxes by strong stratification at the mixed layer base, and its periphery is
stable to shear instability, suggestive of longevity and the ability to carry
water far distances with minimal modification.
PMID- 28401910
TI - Smelting Magnesium Metal using a Microwave Pidgeon Method.
AB - Magnesium (Mg) is a lightweight metal with applications in transportation and
sustainable battery technologies, but its current production through ore
reduction using the conventional Pidgeon process emits large amounts of CO2 and
particulate matter (PM2.5). In this work, a novel Pidgeon process driven by
microwaves has been developed to produce Mg metal with less energy consumption
and no direct CO2 emission. An antenna structure consisting of dolomite as the Mg
source and a ferrosilicon antenna as the reducing material was used to confine
microwave energy emitted from a magnetron installed in a microwave oven to
produce a practical amount of pure Mg metal. This microwave Pidgeon process with
an antenna configuration made it possible to produce Mg with an energy
consumption of 58.6 GJ/t, corresponding to a 68.6% reduction when compared to the
conventional method.
PMID- 28401911
TI - Electrically driven cation exchange for in situ fabrication of individual
nanostructures.
AB - Cation exchange (CE) has been recognized as a particularly powerful tool for the
synthesis of heterogeneous nanocrystals. At present, CE can be divided into two
categories, namely ion solvation-driven CE reaction and thermally activated CE
reaction. Here we report an electrically driven CE reaction to prepare individual
nanostructures inside a transmission electron microscope. During the process, Cd
is eliminated due to Ohmic heating, whereas Cu+ migrates into the crystal driven
by the electrical field force. Contrast experiments reveal that the feasibility
of electrically driven CE is determined by the structural similarity of the
sulfur sublattices between the initial and final phases, and the standard
electrode potentials of the active electrodes. Our experimental results
demonstrate a strategy for the selective growth of individual nanocrystals and
provide crucial insights into understanding of the microscopic pathways leading
to the formation of heterogeneous structures.
PMID- 28401912
TI - Quantum-Dot Light-Emitting Diodes with Nitrogen-Doped Carbon Nanodot Hole
Transport and Electronic Energy Transfer Layer.
AB - Electroluminescence efficiency is crucial for the application of quantum-dot
light-emitting diodes (QD-LEDs) in practical devices. We demonstrate that
nitrogen-doped carbon nanodot (N-CD) interlayer improves electrical and
luminescent properties of QD-LEDs. The N-CDs were prepared by solution-based
bottom up synthesis and were inserted as a hole transport layer (HTL) between
other multilayer HTL heterojunction and the red-QD layer. The QD-LEDs with N-CD
interlayer represented superior electrical rectification and electroluminescent
efficiency than those without the N-CD interlayer. The insertion of N-CD layer
was found to provoke the Forster resonance energy transfer (FRET) from N-CD to QD
layer, as confirmed by time-integrated and -resolved photoluminescence
spectroscopy. Moreover, hole-only devices (HODs) with N-CD interlayer presented
high hole transport capability, and ultraviolet photoelectron spectroscopy also
revealed that the N-CD interlayer reduced the highest hole barrier height. Thus,
more balanced carrier injection with sufficient hole carrier transport feasibly
lead to the superior electrical and electroluminescent properties of the QD-LEDs
with N-CD interlayer. We further studied effect of N-CD interlayer thickness on
electrical and luminescent performances for high-brightness QD-LEDs. The ability
of the N-CD interlayer to improve both the electrical and luminescent
characteristics of the QD-LEDs would be readily exploited as an emerging
photoactive material for high-efficiency optoelectronic devices.
PMID- 28401913
TI - Influence of parental care on offspring hippocampal volume in young adults varies
as a function of overprotection.
AB - Parental care results in increased hippocampal volumes through adaptive stress
responses in developing animals. However, human studies have not yet provided
consistent findings analogous to the animal literature, possibly because parental
care in humans is likely intermingled with parental overprotection, as suggested
by the optimal parenting theory. Here, we tested the hypothesis that the effect
of parental care on offspring hippocampal volume varies as a function of parental
overprotection with a large cohort of young adult participants (N = 257).
Consistent with some previous human studies, we found that parental care in
childhood alone had little association with the hippocampal volume in adulthood.
However, when parental overprotection was low, parental care was positively
correlated with offspring hippocampal volume, whereas there was no association
between parental care and offspring hippocampal volume when parental
overprotection was high. Thus, an interaction exists between parental care and
overprotection in human's hippocampal development, which contributes to the
elucidation of the complex relationship between brain structure and environmental
factors.
PMID- 28401914
TI - A 3D-engineered porous conduit for peripheral nerve repair.
AB - End-to-end neurorrhaphy is the most commonly used method for treating peripheral
nerve injury. However, only 50% of patients can regain useful function after
treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit
to promote the function recovery of the transected peripheral nerve after
neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by
molding with 3D-printed moulds. Due to its porous structure and excellent
mechanical properties, this conduit could be collapsed by the mechanical force
and resumed its original shape after absorption of normal saline. This shape
memory property allowed a simply surgery process for installing the conduits.
Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts
and reduce the risk of scar tissue, which could provide an advantageous
environment for nerve regeneration. The efficiency of the conduits in assisting
peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic
nerve transected model. Results indicated that conduits significantly benefitted
the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on
the static sciatic index (SSI), electrophysiological results and the re
innervation of the gastrocnemius muscle. This work demonstrates a biodegradable
nerve conduit that has potentially clinical application in promoting the
neurorrhaphy.
PMID- 28401915
TI - Substrate Induced Strain Field in FeRh Epilayers Grown on Single Crystal MgO
(001) Substrates.
AB - Equi-atomic FeRh is highly unusual in that it undergoes a first order meta
magnetic phase transition from an antiferromagnet to a ferromagnet above room
temperature (Tr ~ 370 K). This behavior opens new possibilities for creating
multifunctional magnetic and spintronic devices which can utilise both thermal
and applied field energy to change state and functionalise composites. A key
requirement in realising multifunctional devices is the need to understand and
control the properties of FeRh in the extreme thin film limit (tFeRh < 10 nm)
where interfaces are crucial. Here we determine the properties of FeRh films in
the thickness range 2.5-10 nm grown directly on MgO substrates. Our magnetometry
and structural measurements show that a perpendicular strain field exists in
these thin films which results in an increase in the phase transition temperature
as thickness is reduced. Modelling using a spin dynamics approach supports the
experimental observations demonstrating the critical role of the atomic layers
close to the MgO interface.
PMID- 28401916
TI - Stereopsis deficits in patients with schizophrenia in a Han Chinese population.
AB - Although cognitive and sensory deficits have been identified as a core feature of
schizophrenia, only a small portion of visual sensorium has been explored. To
date, studies on visual system of three-dimensional percepts based on two
dimensional information still are limited. This study is the first to examine the
integrity of stereopsis of schizophrenia in a Han Chinese population, and to
further investigate the correlation of stereopsis with clinical symptoms. 100
patients with schizophrenia and 80 healthy controls were recruited. We assessed
stereoacuity using the Titmus Stereopsis Test and clinical symptoms using Chinese
versions of the Scales for the Assessment of Positive and Negative Symptoms (SAPS
and SANS). There was a significant difference in log seconds of arc between two
groups (p < 0.0001). The percentage of patients with correct stereopsis detection
was significantly reduced at 400, 200, 140, 100, 80, 60, 50, and 40 seconds of
arc than healthy controls (all, p < 0.01). Log seconds of arc in patients was not
correlated with total scores and subscores of SAPS and SANS (all, p > 0.05). Our
findings support that patients with schizophrenia have a marked deficit of
stereopsis in a Han Chinese population. However, clinical symptoms do not
influence stereopsis of schizophrenia.
PMID- 28401917
TI - Cooperative roles of the suprachiasmatic nucleus central clock and the adrenal
clock in controlling circadian glucocorticoid rhythm.
AB - The mammalian circadian timing system consists of the central clock in the
hypothalamic suprachiasmatic nucleus (SCN) and subsidiary peripheral clocks in
other tissues. Glucocorticoids (GCs) are adrenal steroid hormones with widespread
physiological effects that undergo daily oscillations. We previously demonstrated
that the adrenal peripheral clock plays a pivotal role in circadian GC rhythm by
driving cyclic GC biosynthesis. Here, we show that the daily rhythm in
circulating GC levels is controlled by bimodal actions of central and adrenal
clockwork. When mice were subjected to daytime restricted feeding to uncouple
central and peripheral rhythms, adrenal GC contents and steroidogenic acute
regulatory protein expression peaked around zeitgeber time 00 (ZT00), consistent
with shifted adrenal clock gene expression. However, restricted feeding produced
two distinct peaks in plasma GC levels: one related to adrenal GC content and the
other around ZT12, which required an intact SCN. Light pulse-evoked activation of
the SCN increased circulating GC levels in both wild-type and adrenal clock
disrupted mutant mice without marked induction of GC biosynthesis. In conclusion,
we demonstrate that adrenal clock-dependent steroidogenesis and a SCN-driven
central mechanism regulating GC release cooperate to produce daily circulatory GC
rhythm.
PMID- 28401918
TI - Crystallisation-enhanced bulk hole mobility in phenothiazine-based organic
semiconductors.
AB - A series of three novel donor-acceptor systems based on C(3)-malononitrile
substituted phenothiazines was synthesised in good overall yields and their
thermal, spectroscopic, and electrochemical properties were characterised. The
compounds were prepared through a sequence of Ullmann-coupling, Vilsmeier-Haack
formylation and Knoevenagel-condensation, followed by Suzuki-coupling reactions
for introduction of aryl substitutents at C(7) position of the phenothiazine. The
introduction of a donor unit at the C(7) position exhibited a weak impact on the
optical and electrochemical characteristics of the compounds and led to amorphous
films with bulk hole mobilities in the typical range reported for phenothiazines,
despite the higher charge delocalisation as attested by computational studies. In
contrast, highly ordered films were formed when using the C(7)-unsubstituted 3
malononitrile phenothiazine, exhibiting an outstanding mobility of 1 * 10-3 cm2 V
1 s-1, the highest reported for this class of compounds. Computational
conformational analysis of the new phenothizanes suggested that free rotation of
the substitutents at the C(7) position suppresses the ordering of the system,
thereby hampering suitable packing of the new materials needed for high charge
carrier mobility.
PMID- 28401920
TI - Occurrence of fibrates and their metabolites in source and drinking water in
Shanghai and Zhejiang, China.
AB - Fibrates, which are widely used lipidaemic-modulating drugs, are emerging
environmental pollutants. However, fibrate concentrations in the environment have
not been thoroughly surveyed. Here, we determined concentrations of the most
commonly used fibrates and their metabolites in source water and drinking water
samples from ten drinking water treatment plants in Shanghai and Zhejiang, China,
using solid-phase extraction and liquid chromatography-tandem mass spectrometry.
All the target compounds were detected in at least some of the source water
samples, at concentrations ranging from 0.04 ng/L (fenofibrate) to 1.53 ng/L
(gemfibrozil). All the compounds except fenofibrate were also detected in at
least some of the drinking water samples, at recoveries ranging from 35.5% to
91.7%, suggesting that these compounds are poorly removed by typical drinking
water treatment processes. In a peroxisome proliferator-activated receptor alpha
agonistic activity assay, the target compounds showed no significant activity at
nanogram per litre concentrations; therefore, our results suggest that the
fibrate concentrations in drinking water in Shanghai and Zhejiang, China do not
significantly affect human health. However, because of the increasing
westernization of the Chinese diet, fibrate use may increase, and thus monitoring
fibrate concentrations in aquatic environments and drinking water in China will
become increasingly important.
PMID- 28401919
TI - Mutations in PMR1 stimulate xylose isomerase activity and anaerobic growth on
xylose of engineered Saccharomyces cerevisiae by influencing manganese
homeostasis.
AB - Combined overexpression of xylulokinase, pentose-phosphate-pathway enzymes and a
heterologous xylose isomerase (XI) is required but insufficient for anaerobic
growth of Saccharomyces cerevisiae on d-xylose. Single-step Cas9-assisted
implementation of these modifications yielded a yeast strain expressing Piromyces
XI that showed fast aerobic growth on d-xylose. However, anaerobic growth
required a 12-day adaptation period. Xylose-adapted cultures carried mutations in
PMR1, encoding a Golgi Ca2+/Mn2+ ATPase. Deleting PMR1 in the parental XI
expressing strain enabled instantaneous anaerobic growth on d-xylose. In pmr1
strains, intracellular Mn2+ concentrations were much higher than in the parental
strain. XI activity assays in cell extracts and reconstitution experiments with
purified XI apoenzyme showed superior enzyme kinetics with Mn2+ relative to other
divalent metal ions. This study indicates engineering of metal homeostasis as a
relevant approach for optimization of metabolic pathways involving metal
dependent enzymes. Specifically, it identifies metal interactions of heterologous
XIs as an underexplored aspect of engineering xylose metabolism in yeast.
PMID- 28401921
TI - Distinct Soil Microbial Communities in habitats of differing soil water balance
on the Tibetan Plateau.
AB - Global change may be a severe threat to natural and agricultural systems, partly
through its effects in altering soil biota and processes, due to changes in water
balance. We studied the potential influence of changing soil water balance on
soil biota by comparing existing sites along a natural water balance gradient in
the Qinghai-Tibetan Plateau. In this study, the community structure of bacteria,
archaea and eukaryotes differed between the different soil water conditions. Soil
moisture was the strongest predictor of bacterial and eukaryotic community
structure, whereas C/N ratio was the key factor predicting variation in the
archaeal community. Bacterial and eukaryotic diversity was quite stable among
different soil water availability, but archaeal diversity was dramatically
different between the habitats. The auxotype of methanogens also varied
significantly among different habitats. The co-varying soil properties among
habitats shaped the community structure of soil microbes, with archaea being
particularly sensitive in terms of community composition, diversity and
functional groups. Bacterial and archaeal phylogenetic community turnover was
mainly driven by deterministic processes while stochastic processes had stronger
effects on eukaryotic phylogenetic community turnover. Our work provides insight
into microbial community, functional group and phylogenetic turnover under
different soil conditions in low-latitude alpine ecosystem.
PMID- 28401922
TI - The Phosphatidylcholine Transfer Protein Stard7 is Required for Mitochondrial and
Epithelial Cell Homeostasis.
AB - Mitochondria synthesize select phospholipids but lack the machinery for synthesis
of the most abundant mitochondrial phospholipid, phosphatidylcholine (PC).
Although the phospholipid transfer protein Stard7 promotes uptake of PC by
mitochondria, the importance of this pathway for mitochondrial and cellular
homeostasis represents a significant knowledge gap. Haploinsufficiency for Stard7
is associated with significant exacerbation of allergic airway disease in mice,
including an increase in epithelial barrier permeability. To test the hypothesis
that Stard7 deficiency leads to altered barrier structure/function downstream of
mitochondrial dysfunction, Stard7 expression was knocked down in a bronchiolar
epithelial cell line (BEAS-2B) and specifically deleted in lung epithelial cells
of mice (Stard7epi?/?). Stard7 deficiency was associated with altered
mitochondrial size and membrane organization both in vitro and in vivo. Altered
mitochondrial structure was accompanied by disruption of mitochondrial
homeostasis, including decreased aerobic respiration, increased oxidant stress,
and mitochondrial DNA damage that, in turn, was linked to altered barrier
integrity and function. Both mitochondrial and barrier defects were largely
corrected by targeting Stard7 to mitochondria or treating epithelial cells with a
mitochondrial-targeted antioxidant. These studies suggest that Stard7-mediated
transfer of PC is crucial for mitochondrial homeostasis and that mitochondrial
dysfunction contributes to altered barrier permeability in Stard7-deficient mice.
PMID- 28401923
TI - The Prevalence of Depression and Depressive Symptoms among Eye Disease Patients:
A Systematic Review and Meta-analysis.
AB - The prevalence of depression among different eye disease patients varies across
studies and has not been systematically reviewed. This study is to provide a
summary of the prevalence of depression among eye disease patients. PubMed,
Medline, Embase and Cochrane Library were searched from January, 1990 to
December, 2015 to identify studies with information on the prevalence of
depression among ophthalmic patients. A random/fixed-effects meta-analysis was
used to estimate the pooled prevalence of depression among eye disease patients.
Heterogeneity was assessed with the I2 test. 28 studies were selected from 3162
references. The overall pooled prevalence of depression or depressive symptoms
with eye disease was 25% (1502/6589 individuals, 95% CI, 0.20-0.30) ranging from
5.4% to 57.0%. Regarding different disease categories, the highest prevalence was
revealed for dry eye disease (DED) with 29%, followed by 25% for glaucoma
patients, 24% for age-related macular degeneration (AMD) patients, 23% for
cataract patients. The increased pooled prevalence of depression was identified
in those with eye diseases compared with healthy controls (OR, 1.59; 95% CI, 1.40
1.81; I2 = 68.5%). Substantial heterogeneity was identified across most estimates
(I2 > 75%). Further research is needed to identify effective strategies for
preventing and treating depression among eye disease patients.
PMID- 28401925
TI - Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine
Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron
Excitability.
AB - Understanding why the quit rate among smokers of menthol cigarettes is lower than
non-menthol smokers requires identifying the neurons that are altered by
nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral
tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using
mouse models, we show that menthol enhances nicotine-induced changes in nicotinic
acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus
nicotine upregulates nAChR number and function on midbrain DA neurons more than
nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron
excitability. In a conditioned place preference (CPP) assay, we observed that
menthol plus nicotine produces greater reward-related behavior than nicotine
alone. Our results connect changes in midbrain DA neurons to menthol-induced
enhancements of nicotine reward-related behavior and may help explain how smokers
of menthol cigarettes exhibit reduced cessation rates.
PMID- 28401924
TI - The Human Coparental Bond Implicates Distinct Corticostriatal Pathways:
Longitudinal Impact on Family Formation and Child Well-Being.
AB - Alloparental care, the cooperative care of offspring by group members other than
the biological mother, has been widely practiced since early hominin evolution to
increase infant survival and thriving. The coparental bond-a relationship of
solidarity and commitment between two adults who join their effort to care for
children-is a central contributor to children's well-being and sociality; yet,
the neural basis of coparenting has not been studied in humans. Here, we followed
84 first-time co-parents (42 couples) across the first 6 years of family
formation, including opposite-sex and same-sex couples, measured brain response
to coparental stimuli, observed collaborative and undermining coparental
behaviors in infancy and preschool, assayed oxytocin (OT) and vasopressin (AVP),
and measured coparenting and child behavior problems at 6 years. Across family
types, coparental stimuli activated the striatum, specifically the ventral
striatum and caudate, striatal nodes implicated in motivational goal-directed
social behavior. Psychophysiological interaction analysis indicated that both
nodes were functionally coupled with the vmPFC in support of the human coparental
bond and this connectivity was stronger as collaborative coparental behavior
increased. Furthermore, caudate functional connectivity patterns differentiated
distinct corticostriatal pathways associated with two stable coparental
behavioral styles; stronger caudate-vmPFC connectivity was associated with more
collaborative coparenting and was linked to OT, whereas a stronger caudate-dACC
connectivity was associated with increase in undermining coparenting and was
related to AVP. Finally, dyadic path-analysis model indicated that the parental
caudate-vmPFC connectivity in infancy predicted lower child externalizing
symptoms at 6 years as mediated by collaborative coparenting in preschool.
Findings indicate that the coparental bond is underpinned by striatal activations
and corticostriatal connectivity similar to other human affiliative bonds;
highlight specific corticostriatal pathways as defining distinct coparental
orientations that underpin family life; chart brain-hormone-behavior
constellations for the mature, child-orientated coparental bond; and demonstrate
the flexibility of this bond across family constellations and its unique
contribution to child well-being.
PMID- 28401926
TI - Association between Cockroach-specific Immunoglobulin E and periodontitis in
Korean male adults Based on Korean National Health and Nutrition Examination
Survey.
AB - Periodontitis is an inflammatory disease affecting the tooth supporting tissues
(periodontium) and associated with chronic diseases such as cardiovascular
disease and insulin resistance. However, there has been no nation-wide population
based epidemiologic study regarding any association between periodontitis and
serum IgE. Among the 8,958 participants in the 2010 Korean National Health and
Nutrition Examination Survey (KNHANES V-1), 1,731 adults aged 19 to 64 who had
measured serum IgE were included in the analysis. Dentists examined the
periodontal status of the participants. Multiple logistic regression analyses
were used to evaluate the odds ratio of periodontitis in association with total
IgE and specific IgE to cockroach and house dust mite. In males, total IgE showed
a positive correlation with the presence of periodontitis. The participants in
the highest tertile of cockroach specific IgE (T3, >31.6 kU/L) had a
significantly increased risk of periodontitis (OR = 2.108; 95% CI, 1.233-3.606).
In females, the inverse association occurred between total IgE and periodontitis
(OR = 0.409; 95% CI, 0.200-0.839). The present study firstly demonstrated the
association between periodontitis and serum IgE, using the Korean nationwide,
population-based, cross-sectional health examination and survey. This study
suggested a positive correlation between periodontitis and cockroach-specific IgE
in Korean male adults.
PMID- 28401927
TI - Stimuli-controlled self-assembly of diverse tubular aggregates from one single
small monomer.
AB - The design and synthesis of new stimuli-responsive hydrogen-bonding monomers that
display a diversity of self-assembly pathways is of central importance in
supramolecular chemistry. Here we describe the aggregation properties of a
simple, intrinsically C2-symmetric enantiopure bicyclic cavity compound bearing a
terminally unsubstituted ureidopyrimidinone fragment fused with a pyrrole moiety
in different solvents and in the absence and presence of C60 and C70 guests. The
tetrameric cyclic aggregate is selectively obtained in chlorinated solvents,
where only part of the available hydrogen bonding sites are utilized, whereas in
toluene or upon addition of C70 guests, further aggregation into tubular
supramolecular polymers is achieved. The open-end cyclic assemblies rearrange
into a closed-shell capsule upon introduction of C60 with an accompanied symmetry
breaking of the monomer. Our study demonstrates that a C60 switch can be used to
simultaneously control the topology and occupancy of tubular assemblies resulting
from the aggregation of small monomers.
PMID- 28401928
TI - Molecular evolutionary mechanisms driving functional diversification of alpha
glucosidase in Lepidoptera.
AB - The digestive tract of lepidopteran insects is unique given its highly alkaline
pH. The adaptive plasticity of digestive enzymes in this environment is crucial
to the highly-efficient nutritional absorption in Lepidoptera. However, little is
known about the molecular adaptation of digestive enzymes to this environment.
Here, we show that lepidopteran alpha-glucosidase, a pivotal digestive enzyme,
diverged into sucrose hydrolase (SUH) and other maltase subfamilies. SUH, which
is specific for sucrose, was only detected in Lepidoptera. It suggests that
lepidopteran insects have evolved an enhanced ability to hydrolyse sucrose, their
major energy source. Gene duplications and exon-shuffling produced multiple
copies of alpha-glucosidase in different microsyntenic regions. Furthermore, SUH
showed significant functional divergence (FD) compared with maltase, which was
affected by positive selection at specific lineages and codons. Nine sites, which
were involved in both FD and positive selection, were located around the ligand
binding groove of SUH. These sites could be responsible for the ligand-binding
preference and hydrolytic specificity of SUH for sucrose, and contribute to its
conformational stability. Overall, our study demonstrated that positive selection
is an important evolutionary force for the adaptive diversification of alpha
glucosidase, and for the exclusive presence of membrane-associated SUHs in the
unique lepidopteran digestive tract.
PMID- 28401929
TI - The effect of L-PRF membranes on bone healing in rabbit tibiae bone defects:
micro-CT and biomarker results.
AB - More insight into the biological fundamentals of leukocyte platelet-rich fibrin
(L-PRF) guided healing is necessary to recommend its application, in particular
in deficient bone sites that need to support implants. This study investigated
the short-term bone healing effect of L-PRF treatment in cylindrical non-critical
sized bone defects with 3 mm diameter and 6 mm depth in tibiae of 18 adult male
New Zealand White rabbits. After a randomization process, 96 bone defects were
prepared and half of them were filled with a L-PRF membrane, while untreated
defects in the opposite tibia served as control group. The rabbits were
euthanized after 7, 14 or 28 days of healing. The bone healing of the cortical
and medullary areas was investigated by micro-CT, while the expression of
molecular markers (RUNX2, VEGFA, COL1A2 and BMP2) was assessed by qRT-PCR.
Treatment with L-PRF did not affect the micro-structural bone characteristics of
the repaired bone tissue, except for a decrease in the trabecular connectivity at
the cortical level after 14 days of healing. At this time, RUNX2 and VEGFA mRNA
levels were significantly lower in the treated defects. L-PRF membranes thus had
a temporary negative influence on the bone microarchitecture (Tb.Pf) and on the
RUNX2 and VEGFA expression during early bone healing. Overall, L-PRF treatment
did not enhance bone regeneration in these non-critical size defects after 28
days.
PMID- 28401930
TI - Nanomechanics of individual aerographite tetrapods.
AB - Carbon-based three-dimensional aerographite networks, built from interconnected
hollow tubular tetrapods of multilayer graphene, are ultra-lightweight materials
recently discovered and ideal for advanced multifunctional applications. In order
to predict the bulk mechanical behaviour of networks it is very important to
understand the mechanics of their individual building blocks. Here we
characterize the mechanical response of single aerographite tetrapods via in situ
scanning electron and atomic force microscopy measurements. To understand the
acquired results, which show that the overall behaviour of the tetrapod is
governed by the buckling of the central joint, a mechanical nonlinear model was
developed, introducing the concept of the buckling hinge. Finite element method
simulations elucidate the governing buckling phenomena. The results are then
generalized for tetrapods of different size-scales and shapes. These basic
findings will permit better understanding of the mechanical response of the
related networks and the design of similar aerogels based on graphene and other
two-dimensional materials.
PMID- 28401931
TI - Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.
AB - Alzheimer's disease (AD), pathologically characterized by amyloid-beta peptide
(Abeta) accumulation, neurofibrillary tangle formation, and neurodegeneration, is
thought to involve early-onset neurovascular abnormalities. Hitherto studies on
AD-associated neurovascular injury have used animal models that exhibit only a
subset of AD-like pathologies and demonstrated some Abeta-dependent vascular
dysfunction and destabilization of neuronal network. The present work focuses on
the early stage of disease progression and uses TgF344-AD rats that recapitulate
a broader repertoire of AD-like pathologies to investigate the cerebrovascular
and neuronal network functioning using in situ two-photon fluorescence microscopy
and laminar array recordings of local field potentials, followed by pathological
analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid
plaques. Concomitant to widespread amyloid deposition and tau
hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in
cortical penetrating arterioles and venules of TgF344-AD rats in comparison to
those in non-transgenic littermates. Blood flow elevation to hypercapnia was
abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the
neuronal network was impaired, evidenced by decreased modulation of theta band
phase on gamma band amplitude. These results demonstrate significant
neurovascular network dysfunction at an early stage of AD-like pathology. Our
study identifies early markers of pathology progression and call for development
of combinatorial treatment plans.
PMID- 28401933
TI - Bcl-xL mediates RIPK3-dependent necrosis in M. tuberculosis-infected macrophages.
AB - Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mphi, which
is essential for successful pathogenesis in tuberculosis. Here we demonstrate
that necrosis of Mtb-infected Mphi is dependent on the action of the cytosolic
Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family
member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mphi are
able to better control bacterial growth in vitro and in vivo. Mechanistically,
cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and
blocks caspase 8-activation and apoptosis via Bcl-xL. Furthermore, necrosis is
associated with stabilization of hexokinase II on the mitochondria as well as
cyclophilin D-dependent mitochondrial permeability transition. Collectively,
these events upregulate the level of reactive oxygen species to induce necrosis.
Thus, in Mtb-infected Mphi, mitochondria are an essential platform for induction
of necrosis by activating RIPK3 function and preventing caspase 8-activation.
PMID- 28401934
TI - Vaginal lactic acid elicits an anti-inflammatory response from human
cervicovaginal epithelial cells and inhibits production of pro-inflammatory
mediators associated with HIV acquisition.
AB - Inflammation in the female reproductive tract (FRT) is associated with increased
HIV transmission. Lactobacillus spp. dominate the vaginal microbiota of many
women and their presence is associated with reduced HIV acquisition. Here we
demonstrate that lactic acid (LA), a major organic acid metabolite produced by
lactobacilli, mediates anti-inflammatory effects on human cervicovaginal
epithelial cells. Treatment of human vaginal and cervical epithelial cell lines
with LA (pH 3.9) elicited significant increases in the production of the anti
inflammatory cytokine IL-1RA. When added simultaneously or prior to stimulation,
LA inhibited the Toll-like receptor agonist-elicited production of inflammatory
mediators IL-6, IL-8, TNFalpha, RANTES, and MIP3alpha from epithelial cell lines
and prevented IL-6 and IL-8 production by seminal plasma. The anti-inflammatory
effect of LA was mediated by the protonated form present at pH<=3.86 and was
observed with both L- and D-isomers. A similar anti-inflammatory effect of LA was
observed in primary cervicovaginal cells and in an organotypic epithelial tissue
model. These findings identify a novel property of LA that acts directly on
epithelial cells to inhibit FRT inflammation and highlights the potential use of
LA-containing agents in the lower FRT as adjuncts to female-initiated strategies
to reduce HIV acquisition.
PMID- 28401932
TI - Inflammasomes and intestinal inflammation.
AB - The inflammasome is a cytosolic multi-protein innate immune rheostat, sensing a
variety of endogenous and environmental stimuli, and regulating homeostasis or
damage control. In the gastrointestinal tract, inflammasomes orchestrate immune
tolerance to microbial and potentially food-related signals or drive the
initiation of inflammatory responses to invading pathogens. When inadequately
regulated, intestinal inflammasome activation leads to a perpetuated inflammatory
response leading to immune pathology and tissue damage. In this review, we
present the main features of the predominant types of inflammasomes participating
in intestinal homeostasis and inflammation. We then discuss current controversies
and open questions related to their functions and implications in disease,
highlighting how pathological inflammasome over-activation or impaired function
impact gut homeostasis, the microbiome ecosystem, and the propensity to develop
gut-associated diseases. Collectively, understanding of the molecular basis of
intestinal inflammasome signaling may be translated into clinical manipulation of
this fundamental pathway as a potential immune modulatory therapeutic
intervention.
PMID- 28401935
TI - Unique invariant natural killer T cells promote intestinal polyps by suppressing
TH1 immunity and promoting regulatory T cells.
AB - CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early
regulatory cells of immune responses. Besides the established roles in the
regulation of inflammation and autoimmune disease, studies have shown that iNKT
cells have important roles in tumor surveillance and the control of tumor
metastasis. Here we found that the absence of iNKT cells markedly decreased the
total number of intestinal polyps in APCMin/+ mice, a model for colorectal
cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17
producing cells, showed a distinct phenotype being CD4+, NK1.1- CD44int, and PD
1lo, and they were negative for the NKT cell transcription factor promyelocytic
leukemia zinc-finger. The absence of iNKT cells was associated with a reduced
frequency of regulatory T (Tregs) cells and lower expression levels of FoxP3
protein and transcript uniquely in the polyps, and a switch to an inflammatory
macrophage phenotype. Moreover, in iNKT cell-deficient APCMin/+ mice, expression
of T-helper (TH) 1-associated genes, such as IFN-gamma and Nos2, was increased in
polyps, concomitantly with elevated frequencies of conventional CD4+ and CD8+ T
cells in this tissue. The results suggest that a population of regulatory iNKT
cells locally promote intestinal polyp formation by enhancing Treg cells and
immunosuppression of antitumor TH1 immunity.
PMID- 28401937
TI - Progesterone-based compounds affect immune responses and susceptibility to
infections at diverse mucosal sites.
AB - Over 100 million women worldwide are currently on progesterone-based
contraceptives to improve their health outcomes through reduced maternal
mortality and family planning. In addition to their role in reproduction,
progesterone-based compounds modulate immune responses throughout the body,
particularly at mucosal sites. By binding to receptors located in immune cells,
including natural killer cells, macrophages, dendritic cells, and T cells, as
well in non-immune cells, such as epithelial and endothelial cells, progesterone
based compounds alter cellular signaling and activity to affect the outcome of
infections at diverse mucosal sites, including the genital, gastrointestinal, and
respiratory tracts. As the use of progesterone-based compounds, in the form of
contraceptives and hormone-based therapies, continue to increase worldwide,
greater consideration should be given to how the immunomodulatory effects these
compounds alter the outcome of diseases at mucosal sites beyond the reproductive
tract, which has profound implications for women's health.
PMID- 28401938
TI - Novel protective mechanism for interleukin-33 at the mucosal barrier during
influenza-associated bacterial superinfection.
AB - Influenza A is a highly contagious respiratory virus that causes seasonal
epidemics and occasional worldwide pandemics. The primary cause of influenza
related mortality is bacterial superinfection. There are numerous mechanisms by
which preceding influenza infection attenuates host defense, allowing for
increased susceptibility to bacterial pneumonia. Herein, we demonstrate that
influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL
33). Restoration of IL-33 during influenza A and methicillin-resistant S. aureus
superinfection enhanced bacterial clearance and improved mortality. Innate
lymphoid Type 2 cells and alternatively activated macrophages are not required
for IL-33-mediated protection during superinfection. We show that IL-33 treatment
resulted in neutrophil recruitment to the lung, associated with improved
bacterial clearance. These findings identify a novel role for IL-33 in
antibacterial host defense at the mucosal barrier.
PMID- 28401936
TI - BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes.
AB - Patients with asthma experience circadian variations in their symptoms. However
it remains unclear how specific aspects of this common airway disease relate to
clock genes, which are critical to the generation of circadian rhythms in
mammals. Here, we used a viral model of acute and chronic airway disease to
examine how circadian clock disruption affects asthmatic lung phenotypes.
Deletion of the core clock gene bmal1 or environmental disruption of circadian
function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus
(SeV) and influenza A virus in mice. Post-natal deletion of bmal1 was sufficient
to trigger increased SeV susceptibility and correlated with impaired control of
viral replication. Importantly, bmal1-/- mice developed much more extensive
asthma-like airway changes post infection, including mucus production and
increased airway resistance. In human airway samples from two asthma cohorts, we
observed altered expression patterns of multiple clock genes. Our results suggest
a role for bmal1 in the development of asthmatic airway disease via the
regulation of lung antiviral responses to common viral triggers of asthma.
PMID- 28401940
TI - Optical nonlinearity enhancement with graphene-decorated silicon waveguides.
AB - Broadband on-chip optical frequency combs (OFCs) are important for expanding the
functionality of photonic integrated circuits. Here, we demonstrate a huge local
optical nonlinearity enhancement using graphene. A waveguide is decorated with
graphene by precisely manipulating graphene's area and position. Our approach
simultaneously achieves both an extremely efficient supercontinuum and ultra
short pulse generation. With our graphene-decorated silicon waveguide (G-SWG), we
have achieved enhanced spectral broadening of femtosecond pump pulses, along with
an eightfold increase in the output optical intensity at a wavelength
approximately 200 nm shorter than that of the pump pulses. We also found that
this huge nonlinearity works as a compressor that effectively compresses pulse
width from 80 to 15.7 fs. Our results clearly show the potential for our G-SWG to
greatly boost the speed and capacity of future communications with lower power
consumption, and our method will further decrease the required pump laser power
because it can be applied to decorate various kinds of waveguides with various
two-dimensional materials.
PMID- 28401939
TI - MDR1 deficiency impairs mitochondrial homeostasis and promotes intestinal
inflammation.
AB - The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux
transporter that is highly expressed in the colon. In mice, loss of MDR1 function
results in colitis with similarities to human inflammatory bowel diseases (IBD).
Here, we show that MDR1 has an unexpected protective role for the mitochondria
where MDR1 deficiency results in mitochondrial dysfunction with increased
mitochondrial reactive oxygen species (mROS) driving the development of colitis.
Exogenous induction of mROS accelerates, while inhibition attenuates colitis in
vivo; these effects are amplified in MDR1 deficiency. In human IBD, MDR1 is
negatively correlated to SOD2 gene expression required for mROS detoxification.
To provide direct evidential support, we deleted intestinal SOD2 gene in mice and
showed an increased susceptibility to colitis. We exploited the genome-wide
association data sets and found many (~5%) of IBD susceptibility genes with
direct roles in regulating mitochondria homeostasis. As MDR1 primarily protects
against xenotoxins via its efflux function, our findings implicate a distinct
mitochondrial toxin+genetic susceptibility interaction leading to mitochondrial
dysfunction, a novel pathogenic mechanism that could offer many new therapeutic
opportunities for IBD.
PMID- 28401941
TI - A comparative study of efficiency droop and internal electric field for InGaN
blue lighting-emitting diodes on silicon and sapphire substrates.
AB - We investigated the efficiency droop and polarization-induced internal electric
field of InGaN blue light-emitting diodes (LEDs) grown on silicon(111) and c
plane sapphire substrates. The efficiency droop of the LED sample grown on
silicon substrates was considerably lower than that of the identically fabricated
LED sample grown on sapphire substrates. Consequently, the LED on silicon showed
higher efficiency at a sufficiently high injection current despite the lower peak
efficiency caused by the poorer crystal quality. The reduced efficiency droop for
the LED on silicon was attributed to its lower internal electric field, which was
confirmed by reverse-bias electro-reflectance measurements and numerical
simulations. The internal electric field of the multiple quantum wells (MQWs) on
silicon was found to be reduced by more than 40% compared to that of the MQWs on
sapphire, which resulted in a more homogenous carrier distribution in InGaN MQWs,
lower Auger recombination rates, and consequently reduced efficiency droop for
the LEDs grown on the silicon substrates. Owing to its greatly reduced efficiency
droop, the InGaN blue LED on silicon substrates is expected to be a good cost
effective solution for future lighting technology.
PMID- 28401942
TI - Probing the symmetry of the potential of localized surface plasmon resonances
with phase-shaped electron beams.
AB - Plasmonics, the science and technology of the interaction of light with metallic
objects, is fundamentally changing the way we can detect, generate and manipulate
light. Although the field is progressing swiftly, thanks to the availability of
nanoscale manufacturing and analysis methods, fundamental properties such as the
plasmonic excitations' symmetries cannot be accessed directly, leading to a
partial, sometimes incorrect, understanding of their properties. Here we overcome
this limitation by deliberately shaping the wave function of an electron beam to
match a plasmonic excitations' symmetry in a modified transmission electron
microscope. We show experimentally and theoretically that this offers selective
detection of specific plasmon modes within metallic nanoparticles, while
excluding modes with other symmetries. This method resembles the widespread use
of polarized light for the selective excitation of plasmon modes with the
advantage of locally probing the response of individual plasmonic objects and a
far wider range of symmetry selection criteria.
PMID- 28401943
TI - Signal coverage approach to the detection probability of hypothetical
extraterrestrial emitters in the Milky Way.
AB - The lack of evidence for the existence of extraterrestrial life, even the
simplest forms of animal life, makes it is difficult to decide whether the search
for extraterrestrial intelligence (SETI) is more a high-risk, high-payoff
endeavor than a futile attempt. Here we insist that even if extraterrestrial
civilizations do exist and communicate, the likelihood of detecting their signals
crucially depends on whether the Earth lies within a region of the galaxy covered
by such signals. By considering possible populations of independent emitters in
the galaxy, we build a statistical model of the domain covered by hypothetical
extraterrestrial signals to derive the detection probability that the Earth is
within such a domain. We show that for general distributions of the signal
longevity and directionality, the mean number of detectable emitters is less than
one even for detection probabilities as large as 50%, regardless of the number of
emitters in the galaxy.
PMID- 28401944
TI - Lignin-graft-Polyoxazoline Conjugated Triazole a Novel Anti-Infective Ointment to
Control Persistent Inflammation.
AB - Lignin, one of the most abundant renewable feedstock, is used to develop a
biocompatible hydrogel as anti-infective ointment. A hydrophilic polyoxazoline
chain is grafted through ring opening polymerization, possess homogeneous
spherical nanoparticles of 10-15 nm. The copolymer was covalently modified with
triazole moiety to fortify the antimicrobial and antibiofilm activities. The
hydrogel was capable of down regulating the expression level of IL-1beta in LPS
induced macrophage cells, and to cause significant reduction of iNOS production.
It supported cellular anti-inflammatory activity which was confirmed with
luciferase assay, western blot, and NF-kappaB analysis. This novel lignin-based
hydrogel tested in-vivo has shown the abilities to prevent infection of burn
wound, aid healing, and an anti-inflammatory dressing material. The hydrogel
reported here provides a new material platform to introduce a cost-effective and
efficient ointment option after undertaking further work to look at its use in
the area of clinical practice.
PMID- 28401945
TI - A Study on Fast Gates for Large-Scale Quantum Simulation with Trapped Ions.
AB - Large-scale digital quantum simulations require thousands of fundamental
entangling gates to construct the simulated dynamics. Despite success in a
variety of small-scale simulations, quantum information processing platforms have
hitherto failed to demonstrate the combination of precise control and scalability
required to systematically outmatch classical simulators. We analyse how fast
gates could enable trapped-ion quantum processors to achieve the requisite
scalability to outperform classical computers without error correction. We
analyze the performance of a large-scale digital simulator, and find that
fidelity of around 70% is realizable for pi-pulse infidelities below 10-5 in
traps subject to realistic rates of heating and dephasing. This scalability
relies on fast gates: entangling gates faster than the trap period.
PMID- 28401947
TI - Increasing large scale windstorm damage in Western, Central and Northern European
forests, 1951-2010.
AB - Using reports of forest losses caused directly by large scale windstorms (or
primary damage, PD) from the European forest institute database (comprising 276
PD reports from 1951-2010), total growing stock (TGS) statistics of European
forests and the daily North Atlantic Oscillation (NAO) index, we identify a
statistically significant change in storm intensity in Western, Central and
Northern Europe (17 countries). Using the validated set of storms, we found that
the year 1990 represents a change-point at which the average intensity of the
most destructive storms indicated by PD/TGS > 0.08% increased by more than a
factor of three. A likelihood ratio test provides strong evidence that the change
point represents a real shift in the statistical behaviour of the time series.
All but one of the seven catastrophic storms (PD/TGS > 0.2%) occurred since 1990.
Additionally, we detected a related decrease in September-November PD/TGS and an
increase in December-February PD/TGS. Our analyses point to the possibility that
the impact of climate change on the North Atlantic storms hitting Europe has
started during the last two and half decades.
PMID- 28401946
TI - Feasibility of placenta-derived mesenchymal stem cells as a tool for studying
pregnancy-related disorders.
AB - The cellular and molecular mechanisms responsible for pregnancy-related disorders
remain unclear. We investigated the feasibility of using placenta-derived
mesenchymal stem cells (MSCs) as a tool to study such pregnancy-related
disorders. We isolated and expanded adequate numbers of cells with characteristic
features of MSCs from the chorionic plate (CP-MSCs), chorionic villi (CV-MSCs),
and decidua basalis (DB-MSCs) of human term placental tissues. All placenta
derived MSCs expressed pregnancy-associated C14MC microRNA (miRNA) (miR-323-3p).
Interestingly, the placenta-specific C19MC miRNAs (miR-518b and miR517a) were
clearly expressed in CP-MSCs and CV-MSCs of foetal origin, but were barely
expressed in DB-MSCs of maternal origin. Furthermore, expression levels of
placenta-specific C19MC miRNAs in CV-MSCs remained stable during the ex vivo
expansion process and across different pregnancy phases (first trimester versus
third trimester). High-efficiency siRNA transfection was confirmed in twice
passaged CV-MSCs with little toxicity, and microarray analysis was used to screen
for miR-518b target genes. Placenta-derived MSCs, especially CV-MSCs, are a
potential tool for investigating the role of placental miRNAs in pregnancy
related disorders.
PMID- 28401948
TI - Development and validation of a method for precise dating of female puberty in
laboratory rodents: The puberty ovarian maturation score (Pub-Score).
AB - Puberty is a key developmental event whose primary regulatory mechanisms remain
poorly understood. Precise dating of puberty is crucial for experimental
(preclinical) studies on its complex neuroendocrine controlling networks. In
female laboratory rodents, external signs of puberty, such as vaginal opening
(VO) and epithelial cell cornification (i.e., first vaginal estrus, FE), are
indirectly related to the maturational state of the ovary and first ovulation,
which is the unequivocal marker of puberty. Whereas in rats, VO and FE are almost
simultaneous with the first ovulation, these events are not so closely associated
in mice. Moreover, external signs of puberty can be uncoupled with first
ovulation in both species under certain experimental conditions. We propose
herein the Pubertal Ovarian Maturation Score (Pub-score), as novel, reliable
method to assess peripubertal ovarian maturation in rats and mice. This method is
founded on histological evaluation of pre-pubertal ovarian maturation, based on
antral follicle development, and the precise timing of first ovulation, by
retrospective dating of maturational and regressive changes in corpora lutea.
This approach allows exact timing of puberty within a time-window of at least two
weeks after VO in both species, thus facilitating the identification and precise
dating of advanced or delayed puberty under various experimental conditions.
PMID- 28401949
TI - Inverting polar domains via electrical pulsing in metallic germanium telluride.
AB - Germanium telluride (GeTe) is both polar and metallic, an unusual combination of
properties in any material system. The large concentration of free-carriers in
GeTe precludes the coupling of external electric field with internal
polarization, rendering it ineffective for conventional ferroelectric
applications and polarization switching. Here we investigate alternate ways of
coupling the polar domains in GeTe to external electrical stimuli through optical
second harmonic generation polarimetry and in situ TEM electrical testing on
single-crystalline GeTe nanowires. We show that anti-phase boundaries, created
from current pulses (heat shocks), invert the polarization of selective domains
resulting in reorganization of certain 71o domain boundaries into 109o
boundaries. These boundaries subsequently interact and evolve with the partial
dislocations, which migrate from domain to domain with the carrier-wind force
(electrical current). This work suggests that current pulses and carrier-wind
force could be external stimuli for domain engineering in ferroelectrics with
significant current leakage.
PMID- 28401950
TI - Auditory conditioned stimulus presentation during NREM sleep impairs fear memory
in mice.
AB - Externally manipulating memories by presenting conditioned stimuli (CS) during
sleep is a new approach to investigating memory processing during sleep. However,
whether presenting a CS during REM or NREM sleep enhances or extinguishes fear
memory has not been clearly delineated. In this study, mice underwent trace fear
conditioning consisting of an auditory CS paired with a foot shock, and the
auditory CS was re-presented during subsequent REM or NREM sleep. Mice that
received auditory cueing during NREM but not REM sleep showed impaired fear
memory upon later presentation of the auditory CS. These findings have
implications for the use of cueing during sleep and advance our understanding of
the role of REM and NREM sleep in memory consolidation.
PMID- 28401951
TI - Magnetically-driven colossal supercurrent enhancement in InAs nanowire Josephson
junctions.
AB - The Josephson effect is a fundamental quantum phenomenon where a dissipationless
supercurrent is introduced in a weak link between two superconducting electrodes
by Andreev reflections. The physical details and topology of the junction
drastically modify the properties of the supercurrent and a strong enhancement of
the critical supercurrent is expected to occur when the topology of the junction
allows an emergence of Majorana bound states. Here we report charge transport
measurements in mesoscopic Josephson junctions formed by InAs nanowires and Ti/Al
superconducting leads. Our main observation is a colossal enhancement of the
critical supercurrent induced by an external magnetic field applied perpendicular
to the substrate. This striking and anomalous supercurrent enhancement cannot be
described by any known conventional phenomenon of Josephson junctions. We
consider these results in the context of topological superconductivity, and show
that the observed critical supercurrent enhancement is compatible with a magnetic
field-induced topological transition.
PMID- 28401952
TI - Correlations in the degeneracy of structurally controllable topologies for
networks.
AB - Many dynamic systems display complex emergent phenomena. By directly controlling
a subset of system components (nodes) via external intervention it is possible to
indirectly control every other component in the system. When the system is linear
or can be approximated sufficiently well by a linear model, methods exist to
identify the number and connectivity of a minimum set of external inputs
(constituting a so-called minimal control topology, or MCT). In general, many
MCTs exist for a given network; here we characterize a broad ensemble of
empirical networks in terms of the fraction of nodes and edges that are always,
sometimes, or never a part of an MCT. We study the relationships between the
measures, and apply the methodology to the T-LGL leukemia signaling network as a
case study. We show that the properties introduced in this report can be used to
predict key components of biological networks, with potentially broad
applications to network medicine.
PMID- 28401954
TI - Prostate cancer: Twist and Skp2 castration resistance.
PMID- 28401953
TI - Overexpression of heparanase enhances T lymphocyte activities and intensifies the
inflammatory response in a model of murine rheumatoid arthritis.
AB - Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The
enzyme is expressed at a low level in normal organs; however, elevated expression
of heparanase has been detected in several inflammatory conditions, e.g. in the
synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied
the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing
human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced
animals developed clinical symptoms, i.e. swelling of joints, and there were no
differences between the Hpa-tg and WT mice in the incidence of disease. However,
Hpa-tg mice displayed an earlier response and developed more severe symptoms.
Examination of cells from thymus, spleen and lymph nodes revealed increased
innate and adaptive immune responses of the Hpa-tg mice, reflected by increased
proportions of macrophages, antigen presenting cells and plasmacytoid dendritic
cells as well as Helios-positive CD4+ and CD8+ T cells. Furthermore, splenic
lymphocytes from Hpa-tg mice showed higher proliferation activity. Our results
suggest that elevated expression of heparanase augmented both the innate and
adaptive immune system and propagated inflammatory reactions in the murine RA
model.
PMID- 28401956
TI - Prostate cancer: Peptidomimetics have potential.
PMID- 28401955
TI - Incontinence in the elderly, 'normal' ageing, or unaddressed pathology?
AB - The prevalence of urinary incontinence and other lower urinary tract symptoms
(LUTS) increases in association with increasing age. This effect is more
noticeable in men after the seventh decade of life and, in women,
postmenopausally. However, the changes in the lower urinary tract, peripheral
nervous system and central nervous system that underpin this observation are both
multifactorial and inadequately understood; much debate exists regarding whether
these observed changes are pathological or are a part of the 'normal' ageing
process; with both health professionals and older people often holding the view
that incontinence is an expected part of normal ageing. Here we aim to summarize
the current level of knowledge regarding the physiological and hormonal changes
that take place during the ageing process and discuss whether the occurrence of
urinary incontinence or other LUTS in later life better reflect part of the
'normal' ageing process or the presence of unaddressed pathology.
PMID- 28401957
TI - Contemporary management of patients with penile cancer and lymph node metastasis.
AB - Penile cancer is a rare disease that causes considerable physical and
psychological patient morbidity, especially at advanced stages. Patients with low
stage nodal metastasis can achieve durable survival with surgery alone, but those
with extensive locoregional metastasis have overall low survival. Contemporary
management strategies for lymph node involvement in penile cancer aim to minimize
the morbidity associated with traditional radical inguinal lymphadenectomy
through appropriate risk stratification while optimizing oncological outcomes.
Modified (or superficial) inguinal lymph node dissection and dynamic sentinel
lymph node biopsy are diagnostic modalities that have been recommended in
patients with high-risk primary penile tumours and nonpalpable inguinal lymph
nodes. In addition, advances in minimally invasive and robot-assisted
lymphadenectomy techniques are being investigated in patients with penile cancer
and might further decrease lymphadenectomy-related adverse effects. The
management of patients with advanced disease has evolved to include multimodal
treatment with systemic chemotherapy before surgical intervention and can include
adjuvant chemotherapy after pelvic lymphadenectomy. The role of radiotherapy in
the neoadjuvant or adjuvant setting remains largely unclear, owing to a lack of
high-level evidence of possible benefits. New targeted therapies have shown
efficacy in squamous cell carcinomas of other sites and might also prove
effective in patients with penile cancer.
PMID- 28401958
TI - Replacing Sanger with Next Generation Sequencing to improve coverage and quality
of reference DNA barcodes for plants.
AB - We estimate the global BOLD Systems database holds core DNA barcodes (rbcL +
matK) for about 15% of land plant species and that comprehensive species coverage
is still many decades away. Interim performance of the resource is compromised by
variable sequence overlap and modest information content within each barcode. Our
model predicts that the proportion of species-unique barcodes reduces as the
database grows and that 'false' species-unique barcodes remain >5% until the
database is almost complete. We conclude the current rbcL + matK barcode is unfit
for purpose. Genome skimming and supplementary barcodes could improve diagnostic
power but would slow new barcode acquisition. We therefore present two novel Next
Generation Sequencing protocols (with freeware) capable of accurate, massively
parallel de novo assembly of high quality DNA barcodes of >1400 bp. We explore
how these capabilities could enhance species diagnosis in the coming decades.
PMID- 28401959
TI - Prenatal stress from trawl capture affects mothers and neonates: a case study
using the southern fiddler ray (Trygonorrhina dumerilii).
AB - Assessing fishing effects on chondrichthyan populations has predominantly focused
on quantifying mortality rates. Consequently, sub-lethal effects of capture
stress on the reproductive capacity of chondrichthyans are largely unknown. We
investigated the reproductive consequences of capture on pregnant southern
fiddler rays (Trygonorrhina dumerilii) collected from Swan Bay, Australia, in
response to laboratory-simulated trawl capture (8 h) followed immediately by air
exposure (30 min). Immediately prior to, and for up to 28 days post trawling, all
females were measured for body mass (BM), sex steroid concentrations (17-beta
estradiol, progesterone, testosterone) and granulocyte to lymphocyte (G:L) ratio.
At parturition, neonates were measured for total length (TL), BM and G:L ratio.
Trawling reduced maternal BM and elevated the G:L ratio for up to 28 days.
Trawling did not significantly affect any sex steroid concentrations relative to
controls. Neonates from trawled mothers were significantly lower in BM and TL
than control animals, and had an elevated G:L ratio. Our results show that
capture of pregnant T. dumerilii can influence their reproductive potential and
affect the fitness of neonates. We suggest other viviparous species are likely to
be similarly affected. Sub-lethal effects of capture, particularly on
reproduction, require further study to improve fisheries management and
conservation of chondrichthyans.
PMID- 28401962
TI - Diamond-like carbon coating under oleic acid lubrication: Evidence for graphene
oxide formation in superlow friction.
AB - The achievement of the superlubricity regime, with a friction coefficient below
0.01, is the Holy Grail of many tribological applications, with the potential to
have a remarkable impact on economic and environmental issues. Based on a
combined high-resolution photoemission and soft X-ray absorption study, we report
that superlubricity can be realized for engineering applications in bearing steel
coated with ultra-smooth tetrahedral amorphous carbon (ta-C) under oleic acid
lubrication. The results show that tribochemical reactions promoted by the oil
lubrication generate strong structural changes in the carbon hybridization of the
ta-C hydrogen-free carbon, with initially high sp3 content. Interestingly, the
macroscopic superlow friction regime of moving mechanical assemblies coated with
ta-C can be attributed to a few partially oxidized graphene-like sheets, with a
thickness of not more than 1 nm, formed at the surface inside the wear scar. The
sp2 planar carbon and oxygen-derived species are the hallmark of these mesoscopic
surface structures created on top of colliding asperities as a result of the
tribochemical reactions induced by the oleic acid lubrication. Atomistic
simulations elucidate the tribo-formation of such graphene-like structures,
providing the link between the overall atomistic mechanism and the macroscopic
experimental observations of green superlubricity in the investigated ta-C/oleic
acid tribological systems.
PMID- 28401963
TI - Mapping cell behavior across a wide range of vertical silicon nanocolumn
densities.
AB - Over the past decade, vertical nanostructures have provided novel approaches for
biomedical applications such as intracellular delivery/detection, specific cell
capture, membrane potential measurement, and cellular activity regulation.
Although the feasibility of the vertical nanostructures as a new biological tool
has been thoroughly demonstrated, a better understanding of cell behavior on
vertical nanostructures, in particular the effects of geometry, is essential for
advanced applications. To investigate the cell behavior according to the
variation of the spacing between vertical nanostructures, we have interfaced
fibroblasts (NIH3T3) with density-controlled vertical silicon nanocolumn arrays
(vSNAs). Over a wide range of vSNA densities, we observe three distinct cell
settling regimes and investigate both overall cell behavior (adhesions,
morphology, and mobility) and detailed biomacromolecule variance (F-actin and
focal adhesion) across these regimes. We expect that these systematic
observations could serve as a guide for improved nanostructure array design for
the desired cell manipulation.
PMID- 28401961
TI - Development and validation of a prognostic model for predicting 30-day mortality
risk in medical patients in emergency department (ED).
AB - The primary aim of this prospective study is to develop and validate a new
prognostic model for predicting the risk of mortality in Emergency Department
(ED) patients. The study involved 1765 patients in the development cohort and
1728 in the validation cohort. The main outcome was mortality up to 30 days after
admission. Potential risk factors included clinical characteristics, vital signs,
and routine haematological and biochemistry tests. The Bayesian Model Averaging
method within the Cox's regression model was used to identify independent risk
factors for mortality. In the development cohort, the incidence of 30-day
mortality was 9.8%, and the following factors were associated with a greater risk
of mortality: male gender, increased respiratory rate and serum urea, decreased
peripheral oxygen saturation and serum albumin, lower Glasgow Coma Score, and
admission to intensive care unit. The area under the receiver operating
characteristic curve for the model with the listed factors was 0.871 (95% CI,
0.844-0.898) in the development cohort and 0.783 (95% CI, 0.743-0.823) in the
validation cohort. Calibration analysis found a close agreement between predicted
and observed mortality risk. We conclude that the risk of mortality among ED
patients could be accurately predicted by using common clinical signs and
biochemical tests.
PMID- 28401964
TI - Water and catalytic isomerization of linear allylic alcohols by [RuCp(H2O
kappaO)(PTA)2]+ (PTA = 1,3,5-triaza-7-phosphaadamantane).
AB - A new water soluble complex [RuCp(H2O-kappaO)(PTA)2]+ (1) (PTA = 1,3,5-triaza-7
phosphaadamantane) has been synthesized and fully characterized by NMR and IR.
The crystal structure of 1(CF3SO3).3.5H2O was characterized by single crystal X
ray determination. The catalytic activity of this complex was evaluated for the
isomerisation of linear allylic alcohols from 3-buten-2-ol to 1-octen-3-ol into
the correspondent ketones under both an inert atmosphere and in air, using as
solvents: water, the substrate, mixtures of water/substrate, MeOH and mixtures of
MeOH/water. An isomerization experiment on a mixture of all the studied allylic
alcohols was also carried out.
PMID- 28401966
TI - Stereodivergent synthesis of right- and left-handed iminoxylitol heterodimers and
monomers. Study of their impact on beta-glucocerebrosidase activity.
AB - A library of dimers and heterodimers of both enantiomers of 2-O-alkylated
iminoxylitol derivatives has been synthesised and evaluated on beta
glucocerebrosidase (GCase), the enzyme responsible for Gaucher disease (GD).
Although the objective was to target simultaneously the active site and a
secondary binding site of the glucosidase, the (-)-2-iminoxylitol moiety seemed
detrimental for imiglucerase inhibition and no significant enhancement was
obtained in G202R, N370S and L444P fibroblasts. However, all compounds having at
least one (+)-2-O-alkyl iminoxylitol are GCase inhibitors in the nano molar range
and are significant GCase activity enhancers in G202R fibroblats, as confirmed by
a decrease of glucosylceramide levels and by co-localization studies.
PMID- 28401960
TI - Sperm whale long-range echolocation sounds revealed by ANTARES, a deep-sea
neutrino telescope.
AB - Despite dedicated research has been carried out to adequately map the
distribution of the sperm whale in the Mediterranean Sea, unlike other regions of
the world, the species population status is still presently uncertain. The
analysis of two years of continuous acoustic data provided by the ANTARES
neutrino telescope revealed the year-round presence of sperm whales in the
Ligurian Sea, probably associated with the availability of cephalopods in the
region. The presence of the Ligurian Sea sperm whales was demonstrated through
the real-time analysis of audio data streamed from a cabled-to-shore deep-sea
observatory that allowed the hourly tracking of their long-range echolocation
behaviour on the Internet. Interestingly, the same acoustic analysis indicated
that the occurrence of surface shipping noise would apparently not condition the
foraging behaviour of the sperm whale in the area, since shipping noise was
almost always present when sperm whales were acoustically detected. The
continuous presence of the sperm whale in the region confirms the ecological
value of the Ligurian sea and the importance of ANTARES to help monitoring its
ecosystems.
PMID- 28401967
TI - PtCl4-catalyzed skeleton rearrangement-cyclization of tertiary indolyl-3
alkynols.
AB - An unexpected PtCl4-catalyzed cyclization reaction of tertiary indol-2-yl-3
alkynols occurred smoothly in toluene to form various poly-substituted carbazole
derivatives efficiently. A possible mechanism involving the formation of a spiro
tricyclic intermediate via indole C-2 attack, highly selective ring expansion and
then 1,2-migration has been proposed for the formation of carbazoles.
PMID- 28401968
TI - Tight binding of heme to Staphylococcus aureus IsdG and IsdI precludes design of
a competitive inhibitor.
AB - The micromolar equilibrium constants for heme dissociation from IsdG and IsdI
reported in the literature call into question whether these enzymes are actually
members of the iron-regulated surface determinant system of Staphylococcus
aureus, which harvests heme iron from a host during infection. In order to
address this question, the heme dissociation constants for IsdG and IsdI were
reevaluated using three approaches. The heme dissociation equilibrium constants
were measured using a UV/Vis absorption-detected assay analyzed with an
assumption-free model, and using a newly developed fluorescence-detected assay.
The heme dissociation rate constants were estimated using apomyoglobin
competition assays. Analyses of the UV/Vis absorption data revealed a critical
flaw in the previous measurements; heme is 99.9% protein-bound at the micromolar
concentrations needed for UV/Vis absorption spectroscopy, which renders accurate
equilibrium constant measurement nearly impossible. However, fluorescence can be
measured for more dilute samples, and analyses of these data resulted in
dissociation equilibrium constants of 1.4 +/- 0.6 nM and 12.9 +/- 1.3 nM for IsdG
and IsdI, respectively. Analyses of the kinetic data obtained from apomyoglobin
competition assays estimated heme dissociation rate constants of 0.022 +/- 0.002
s-1 for IsdG and 0.092 +/- 0.008 s-1 for IsdI. Based upon these data, and what is
known regarding the post-translational regulation of IsdG and IsdI, it is
proposed that only IsdG is a member of the heme iron acquisition pathway and IsdI
regulates heme homeostasis. Furthermore, the nanomolar dissociation constants
mean that heme is bound tightly by IsdG and indicates that competitive inhibition
of this protein will be difficult. Instead, uncompetitive inhibition based upon a
detailed understanding of enzyme mechanism is a more promising antibiotic
development strategy.
PMID- 28401969
TI - Organomagnesium amide catalyzed cross-dehydrocoupling of organosilanes with
amines.
AB - The synthesis of novel heteroleptic organomagnesium(ii) amide complexes
[IMesMg(Ar){N(SiMe3)2}]; (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2
ylidene), Ar = 2,6-Me2C6H3 (Xyl) (1) and 2,4,6-Me3C6H2 (Mes) (2) is reported.
Both compounds 1 and 2 were confirmed by multinuclear (1H, 13C and 29Si) magnetic
resonance spectroscopy, elemental analysis and single crystal X-ray structural
analysis. Furthermore, the organomagnesium amide pre-catalyzed cross
dehydrogenative coupling of organosilanes with amines has been investigated.
PMID- 28401970
TI - Integrating multiple omics data for the discovery of potential Beclin-1
interactions in breast cancer.
AB - Breast cancer has been reported as one of the most frequently diagnosed malignant
diseases and the leading cause of cancer death in women all around the world.
Furthermore, this complicated cancer is divided into multiple subtypes which
present different clinical symptoms and need correspondingly directed therapy. We
took BECN1, a core gene in autophagy performing a tumor inhibitory effect, as a
starting point. The study in this paper aims to identify genes related to breast
cancer and its multiple subtypes by integrating multiple omics data using the
least absolute shrinkage and selection operator (LASSO), which is a statistical
method that can integrate more than two types of omics data. All the data is
obtained from The Cancer Genome Atlas (TCGA) platform which stores clinical and
molecular tumor data. The model constructed is based on three kinds of data
including mRNA-gene expression with a dependent variable level, DNA methylation
and copy number alterations as independent variables. Finally, we propose four
subnets of four subtypes of breast cancer, and consider as a result of microarray
analysis that AFF3 is associated with BECN1 in breast cancer, and may be a
potential therapeutic target. This finding may provide some potential targeted
therapeutics for the four different subtypes of breast cancer at the genetic
level. In conclusion, finding out the major role Beclin-1 plays in breast cancer
subtypes is of great value. The results obtained are instructive for further
research and may provide excellent results in clinical applications, as well as
testing in animal experiments, and may also indicate a new method to perform
bioinformatics analysis.
PMID- 28401971
TI - Imaging metals in biology: pictures of metals in health and disease.
PMID- 28401972
TI - Metal-like electrical conductivity in LaxSr2-xTiMoO6 oxides for high temperature
thermoelectric power generation.
AB - Increasing electrical conductivity in oxides, which are inherently insulators,
can be a potential route in developing oxide-based thermoelectric power
generators with higher energy conversion efficiency. In the present work,
environmentally friendly non-toxic double perovskite LaxSr2-xTiMoO6 (LSTM)
ceramics were synthesized using a solid-state reaction route by optimizing the
sintering temperature and atmosphere for high temperature thermoelectric
applications. Rietveld refinement of XRD data confirmed a single-phase solid
solution with a cubic structure in these double perovskites with the space-group
Pm3[combining macron]m. SEM studies showed a highly dense microstructure in these
ceramics. High electrical conductivity on the order of 105 S m-1 and large
carrier concentration (~1022 cm-3) were obtained in these materials. The
temperature-dependent electrical conductivity measurement showed that the LSTM
ceramics exhibit a semiconductor to metal transition. Thermopower (S)
measurements demonstrated the conductivity switching from a p-type to n-type
behavior at higher temperature. A temperature dependent Seebeck coefficient was
further explained using a model for coexistence of both types of charge carriers
in these oxides. A conductivity mechanism of these double perovskites was found
to be governed by a small polaron hopping model.
PMID- 28401973
TI - One-pot synthesis of thiazino[2,3,4-hi]indole derivatives through a tandem
oxidative coupling/heteroannulation process.
AB - A novel and expedient one-pot synthesis of thiazino[2,3,4-hi]indole derivatives
from o-haloaryl enamines and o-bromothiophenols has been developed. The tandem
oxidative coupling/heteroannulation reactions exhibit high selectivity and good
efficiency. The polycyclic heterocyclic products obtained might be useful in
medicinal chemistry and materials science.
PMID- 28401974
TI - Promoting power density by cleaving LiCoO2 into nano-flake structure for high
performance supercapacitor.
AB - LiCoO2 (LCO) usually can deliver high energy density but low power density in Li
ion batteries (LIBs). Whether LCO could be used as electrode material for high
performance supercapacitors is dependent on promoting its power density. Owing to
Faradaic redox reactions taking place on its surfaces or inside crystals through
ion intercalation/deintercalation from the surfaces, increasing the specific area
of LCO is a key factor to promote its rate capability. Herein, we report a facile
strategy to prepare LCO nano-flakes with high specific area exceeding that of
currently used micro-scale particles in LIBs. LCO as a nano-flake structure is
expected to have a high fraction of Li atom exposure, which benefits fast redox
reactions taking place on the surfaces. An LCO-based electrode exhibits an
excellent specific capacitance of 581.3 F g-1 at 0.5 A g-1, high power density of
2262 W kg-1 at an energy density of 41.0 Wh kg-1, and good cycling stability
(83.9% capacitance retention at 6 A g-1 after 2000 cycles) in LiCl aqueous
electrolyte. Faradaic redox behaviors have been analyzed, indicating an ideal
diffusion-controlled process. Moreover, a full solid-state symmetric
supercapacitor is assembled using LCO nano-flake-based electrodes, which presents
good performance with light weight and flexibility. Impressively, three charged
supercapacitors in series can light 100 green light emitting diodes for 14 min.
LCO in nano-flake structure form with high power density could be an excellent
material for superior supercapacitors.
PMID- 28401976
TI - Frontiers of supramolecular chemistry at solid surfaces.
AB - The application of supramolecular chemistry on solid surfaces represents an
exciting field of research that continues to develop in new and unexpected
directions. This review highlights recent advances in the field which range from
the fundamental aspects of the thermodynamics of self-assembly through to the
development of new materials with potential application as new materials. The
unique aspects of working on solid surfaces are highlighted and advances in the
assembly of many component systems and highly complex fractal-like and
quasicrystalline systems discussed. The unique features of working in the surface
based environment and the utilisation of scanning probe microscopies as a primary
characterisation tool are highlighted.
PMID- 28401975
TI - Imidazolium-labeled glycosides as probes to harness glycosyltransferase activity
in human breast milk.
AB - Imidazolium-labeled (ITag-) glycosides are used to harness the
glycosyltransferase activity directly from human breast milk. The covalently
attached ionic labels provide a bifunctional chemical handle that is used to
monitor reaction progress by MS, as well as aid in product purification from
complex mixtures. The technology is exemplified in the synthesis of biologically
relevant oligosaccharide analogs, LacNAc-ITag, ITag-Lewisx and ITag-Lewisa, in a
matter of days from human breast milk without having to isolate specific enzymes.
PMID- 28401977
TI - Benzylene-linked [PNP] scaffolds and their cyclometalated zirconium and hafnium
complexes.
AB - The benzylene-linked [PNP] scaffolds HN(CH2-o-C6H4PPh2)2 ([A]H) and HN(C6H4-o
CH2PPh2)2 ([B]H) have been used for the synthesis of zirconium and hafnium
complexes. For both ligands, the dimethylamides [A]M(NMe2)3 ([A]1-M) and
[B]M(NMe2)3 ([B]1-M) were prepared and converted to the iodides [A]MI3 ([A]2-M)
and [B]MI3 ([B]2-M) (M = Zr, Hf). Starting from these iodides, the corresponding
benzyl derivatives [A]MBn3 ([A]3-M) and [B]MBn3 ([B]3-M) (M = Zr, Hf) were
obtained via reaction with Bn2Mg(OEt2)2. For zirconium, the benzylic ligand
positions in [A]3-Zr and [B]3-Zr were found to cyclometalate readily, which led
to the corresponding kappa4-[PCNP]ZrBn2 complexes [A]4-Zr and [B]4-Zr. As these
complexes failed to hydrogenate cleanly, cyclometalated derivatives with only one
alkyl substituent were targeted and the mixed benzyl chlorides kappa4-[PCNP]MBnCl
([B]5-M, M = Zr, Hf) were obtained in the case of ligand [B]. Upon hydrogenation
of [B]5-Zr, the eta6-tolyl complex [B]Zr(eta6-C7H8)Cl ([B]6-Zr) was generated
cleanly, but the corresponding hafnium complex [B]5-Hf was found to decompose
unselectively in the presence of H2. Using a closely related carbazole-based
[PNP] ligand, Gade and co-workers have shown recently that zirconium eta6-arene
complexes similar to [B]6-Zr may serve as zirconium(ii) synthons, namely when
reacted with 2,6-Dipp-NC (L) or pyridine (py). Both these substrates were shown
to react cleanly with [B]6-Zr, which led to the formation of the bis-isocyanide
complex [B]ZrCl(L)2 ([B]7-Zr) and the 2,2'-bipyridine derivative [B]ZrCl(bipy)
([B]8-Zr), respectively. Upon reaction of [B]Zr(eta6-C7H8)Cl ([B]6-Zr) with
NaBEt3H, the cyclometalated derivative kappa4-[PCNP]Zr(eta6-C7H8) ([B]9-Zr) was
isolated. In an attempt to synthesise terminal hydrides, complexes [A]MI3 ([A]2
M) were treated with KBEt3H, which led to the isolation of the cyclometalated
hydrido complexes kappa4-[PCNP]M(H)(kappa3-Et3BH) ([A]10-M; M = Zr, Hf) featuring
a kappa3-bound triethyl borohydride moiety.
PMID- 28401978
TI - Cobalt-catalysed Markovnikov selective hydroboration of vinylarenes.
AB - A bipyridiyl-oxazoline cobalt catalyst tBuBPOCoCl2 has been developed for the
Markovnikov selective hydroboration of alkenes using pinacolborane and NaOtBu as
the in situ activator with up to >98 : 2 branched : linear selectivity (24
examples, 45-92% isolated yield).
PMID- 28401979
TI - Cryogenic luminescent thermometers based on multinuclear Eu3+/Tb3+ mixed
lanthanide polyoxometalates.
AB - Here, the excellent thermal sensing capability of a multinuclear lanthanide
polyoxometalate in the cryogenic region (<100 K) is presented for the first time.
Up till now, no lanthanide polyoxometalates have been studied for their use as
ratiometric luminescent thermometers. The investigated Tb3+ polyoxometalate
cluster is doped with 1.6% (P1) and 8.4% (P2) of Eu3+ ions. When excited into the
Mo-O charge transfer bands, at room temperature only the emission of the Eu3+
ions is observed suggesting a very efficient energy transfer between Mo-O->Tb3+
>Eu3+. Only in the cryogenic region the emission of Tb3+ is also witnessed.
PMID- 28401980
TI - The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal
model of epilepsy.
AB - OBJECTIVE: Nonadherence to prescribed dosing regimens is a significant problem in
the treatment of pediatric and adult chronic epilepsy, and can result in severe
consequences to patient outcomes. In this first-of-kind preclinical study, the
impact of nonadherence on seizure control was studied by simulating human
patterns of nonadherence in an animal epilepsy model. METHODS: In study 1, three
different patterns of nonadherence were modeled in newly diagnosed epileptic rats
treated with carbamazepine: perfect adherence (100% of pellets contained
carbamazepine), variable nonadherence (50% of pellets contained carbamazepine
with different dosing patterns between animals), and complete nonadherence (0% of
pellets contained carbamazepine). In study 2, a cohort of newly diagnosed
epileptic rats were subjected to a "drug holiday" nonadherence paradigm, that is,
a 2-week on (100%), 2-week off (0%), and 2-week on (100%) carbamazepine paradigm.
RESULTS: In the first experiment, the 100% (0.3 +/- 0.2 SD convulsive seizures
per day) adherent cohort demonstrated better seizure control than either the 0%
(1.1 +/- 0.8 SD) or 50% (0.8 +/- 0.6 SD) adherent cohorts, which had similar
levels of seizure control. In the second study, poor seizure control was
exhibited during the second 2 weeks; that is, the drug holiday epoch; however,
this did not negatively affect restoration of seizure control upon reinstatement
of CBZ. SIGNIFICANCE: The results from this pilot investigation suggest that
nonadherence to carbamazepine is associated with significant negative but
reversible effects on seizure control in an animal model of epilepsy.
Furthermore, these results demonstrate that animal studies of nonadherence can
yield potentially important and translatable insights into the consequences of
nonadherence on seizure control.
PMID- 28401981
TI - Changes in richness and community composition of ectomycorrhizal fungi among
altitudinal vegetation types on Mount Kinabalu in Borneo.
AB - The distribution patterns of tropical ectomycorrhizal (ECM) fungi along
altitudinal gradients remain largely unknown. Furthermore, despite being an
iconic site for biodiversity research, virtually nothing is known about the
diversity and spatial patterns of fungi on Mt Kinabalu and neighbouring mountain
ranges. We carried out deep DNA sequencing of soil samples collected between 425
and 4000 m above sea level to compare richness and community composition of ECM
fungi among altitudinal forest types in Borneo. In addition, we tested whether
the observed patterns are driven by habitat or by geometric effect of overlapping
ranges of species (mid-domain effect). Community composition of ECM fungi was
strongly correlated with elevation. In most genera, richness peaked in the mid
elevation montane forest zone, with the exception of tomentelloid fungi, which
showed monotonal decrease in richness with increasing altitude. Richness in lower
mid- and mid-elevations was significantly greater than predicted under the mid
domain effect model. We provide the first insight into the composition of ECM
fungal communities and their strong altitudinal turnover in Borneo. The high
richness and restricted distribution of many ECM fungi in the montane forests
suggest that mid-elevation peak richness is primarily driven by environmental
characteristics of this habitat and not by the mid-domain effect.
PMID- 28401982
TI - Consequences of divergence and introgression for speciation in Andean cloud
forest birds.
AB - Divergence with gene flow is well documented and reveals the influence of
ecological adaptation on speciation. Yet, it remains intuitive that gene exchange
inhibits speciation in many scenarios, particularly among ecologically similar
populations. The influence of gene flow on the divergence of populations facing
similar selection pressures has received less empirical attention than scenarios
where differentiation is coupled with local environmental adaptation. I used a
paired study design to test the influence of genomic divergence and introgression
on plumage differentiation between ecologically similar allopatric replacements
of Andean cloud forest birds. Through analyses of short-read genome-wide
sequences from over 160 individuals in 16 codistributed lineages, I found that
plumage divergence is associated with deep genetic divergence, implicating a
prominent role of geographic isolation in speciation. By contrast, lineages that
lack plumage divergence across the same geographic barrier are more recently
isolated or exhibit a signature of secondary genetic introgression, indicating a
negative relationship between gene flow and divergence in phenotypic traits
important to speciation. My results suggest that the evolutionary outcomes of
cycles of isolation and divergence in this important theatre of biotic
diversification are sensitive to time spent in the absence of gene flow.
PMID- 28401983
TI - Using confirmatory factor analysis to validate the Chamberlin affective
instrument for mathematical problem solving with academically advanced students.
AB - BACKGROUND: Student affect plays a considerable role in mathematical problem
solving performance, yet is rarely formally assessed. In this manuscript, an
instrument and its properties are discussed to enable educational psychologists
the opportunity to assess student affect. AIMS: The study was conducted to norm
the CAIMPS (instrument) with gifted students. In so doing, educational
psychologists are informed of the process and the instrument's properties.
SAMPLE: The sample was comprised of 160 middle-grade (7 and 8) students,
identified as gifted, in the United States. METHODS: After completing one of four
model-eliciting activities (MEAs), all participants completed the CAIMPS
(Chamberlin Affective Instrument for Mathematical Problem Solving). Data were
analysed using confirmatory factor analysis to ascertain the number of factors in
the instrument. The normed fit index (0.6939), non-normed fit index (0.8072), and
root mean square error approximation (.076) were at or near the acceptable
levels. Alpha levels for factors were also robust (.637-.923). RESULTS AND
CONCLUSION: Data suggest that the instrument was a good fit for use with
mathematics students in middle grades when solving problems. Perhaps the most
impressive characteristic of the instrument was that the four factors (AVI:
anxiety, value, and interest), SS (self-efficacy and self-esteem), ASP
(aspiration), and ANX (anxiety) did not correlate highly with one another, which
defies previous hypotheses in educational psychology.
PMID- 28401984
TI - The Methuselah of plant diaspores: Sphagnum spores can survive in nature for
centuries.
PMID- 28401985
TI - Alcohol Demand, Future Orientation, and Craving Mediate the Relation Between
Depressive and Stress Symptoms and Alcohol Problems.
AB - BACKGROUND: Elevated depression and stress have been linked to greater levels of
alcohol problems among young adults even after taking into account drinking
level. This study attempts to elucidate variables that might mediate the relation
between symptoms of depression and stress and alcohol problems, including alcohol
demand, future time orientation, and craving. METHODS: Participants were 393
undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2
binge-drinking episodes (4/5+ drinks for women/men, respectively) in the previous
month. Participants completed self-report measures of stress and depression,
alcohol demand, future time orientation, craving, and alcohol problems. RESULTS:
In separate mediation models that accounted for gender, race, and weekly alcohol
consumption, future orientation and craving significantly mediated the relation
between depressive symptoms and alcohol problems. Alcohol demand, future
orientation, and craving significantly mediated the relation between stress
symptoms and alcohol problems. CONCLUSIONS: Heavy-drinking young adults who
experience stress or depression are likely to experience alcohol problems, and
this is due in part to elevations in craving and alcohol demand, and less
sensitivity to future outcomes. Interventions targeting alcohol misuse in young
adults with elevated levels of depression and stress should attempt to increase
future orientation and decrease craving and alcohol reward value.
PMID- 28401987
TI - Discrimination of Saccharides by a Simple Array.
AB - We report the development of a two-component probe system as fluorescence turn-on
assay of simple saccharides. The quenching of an anionic conjugated water-soluble
polymer by a cationic quencher has been reported previously. Three different
boronic acid functionalized benzyl viologens and three conjugated polymers of the
poly(aryleneethynylene) type form nine non-fluorescent complexes. This small
library discriminates nine different simple saccharides in aqueous solutions by
fluorescence turn-on in a displacement assay. The saccharides can be
discriminated and identified with this simple system.
PMID- 28401986
TI - Auditory processing following infantile spasms: An event-related potential study.
AB - OBJECTIVES: To investigate acoustic auditory processing in patients with recent
infantile spasms (IS). METHODS: Patients (n = 22; 12 female; median age 8 months;
range 5-11 months) had normal preceding development, brain magnetic resonance
imaging (MRI), and neurometabolic testing (West syndrome of unknown cause, uWS).
Controls were healthy babies (n = 22; 11 female; median age 6 months; range 3-12
months). Event-related potentials (ERPs) and psychometry (Bayley Scales of Infant
Development, Second Edition, BSID-II) took place at a month following IS
remission. RESULTS: Following a repeated pure tone, uWS patients showed less
suppression of the N100 at the mid-temporal electrodes (p = 0.006), and a
prolonged response latency (p = 0.019). Their novelty P300 amplitude over the mid
temporal electrodes was halved (p = 0.001). The peak of the novelty P300 to
environmental broadband sounds emerged later over the left temporal lobe in
patients (p = 0.015), the lag correlating with duration of spasms (r = 0.547, p =
0.015). BSID-II scores were lower in patients (p < 0.001), with no correlation to
ERP. SIGNIFICANCE: Complex acoustic information is processed poorly following IS.
This would impair language. Treatment did not reverse this phenomenon, but may
have limited its severity. The data are most consistent with altered connectivity
of the cortical acoustic processing areas induced by IS.
PMID- 28401988
TI - A rapid nuclear staining test using cationic dyes contributes to efficient STR
analysis of telogen hair roots.
AB - Telogen hairs presented in the crime scene are commonly encountered as trace
evidence. However, short tandem repeat (STR) profiling of the hairs currently
have low and limited use due to poor success rate. To increase the success rate
of STR profiling of telogen hairs, we developed a rapid and cost-effective method
to estimate the number of nuclei in the hair roots. Five cationic dyes, Methyl
green (MG), Harris hematoxylin (HH), Methylene blue (MB), Toluidine blue (TB),
and Safranin O (SO) were evaluated in this study. We conducted a screening test
based on microscopy and the percentage of loss with nuclear DNA, in order to
select the best dye. MG was selected based on its specific nuclei staining and
low adverse effect on the hair-associated nuclear DNA. We examined 330 scalp and
100 pubic telogen hairs with MG. Stained hairs were classified into five groups
and analyzed by STR. The fast staining method revealed 70% (head hair) and 33.4%
(pubic hair) of full (30 alleles) and high partial (18-29 alleles) STR profiling
proportion from the lowest nuclei count group (one to ten nuclei). The results of
this study demonstrated a rapid, specific, nondestructive, and high yield DNA
profiling method applicable for screening telogen hairs.
PMID- 28401989
TI - Cross-lagged relations between teacher and parent ratings of children's task
avoidance and different literacy skills.
AB - BACKGROUND: Task avoidance is a significant predictor of literacy skills.
However, it remains unclear whether the relation between the two is reciprocal
and whether it is affected by the type of literacy outcome, who is rating
children's task avoidance, and the children's gender. AIM: The purpose of this
longitudinal study was to examine the cross-lagged relations between teacher and
parent ratings of children's task avoidance and different literacy skills.
SAMPLE: One hundred and seventy-two Greek children (91 girls, 81 boys) were
followed from Grade 1 to Grade 3. METHODS: Children were assessed on reading
accuracy, reading fluency, and spelling to dictation. Parents and teachers rated
the children's task-avoidant behaviour. RESULTS: Results of structural equation
modelling showed that the cross-lagged relations varied as a function of the
literacy outcome, who rated the children's task avoidance, and children's gender.
Earlier reading and spelling performance predicted subsequent parent-rated task
avoidance, but parent-rated task avoidance did not predict subsequent reading and
spelling performance (with the exception of spelling in Grade 3). Teacher-rated
task avoidance and reading fluency/spelling had a reciprocal relationship over
time. In addition, the effects of teacher-rated task avoidance on future spelling
were significantly stronger in boys than in girls. CONCLUSIONS: This suggests
that poor reading and spelling performance can lead to subsequent task avoidance
in both classroom and home situations. The fact that task avoidance permeates
across different learning environments is alarming and calls for joint action
from both parents and teachers to mitigate its negative impact on learning.
PMID- 28401990
TI - Sediment toxicity identification evaluation (TIE phases I and II) based on
microscale bioassays for diagnosing causes of toxicity in coastal areas affected
by domestic sewage.
AB - Domestic sewage is a major problem in highly urbanized coastal areas worldwide.
In the present study, toxicity identification evaluation (TIE) phases I and II
were applied to sediment interstitial water from 2 locations along the Sao Paulo
coast in southeastern Brazil: the sewage outfalls from the city of Santos, a
densely urbanized area, and the city of Bertioga, a less urbanized area. An
adapted microscale sea urchin embryo-larval development bioassay was employed.
Phase TIE-I manipulations were 1) ethylenediamine tetraacetic acid (EDTA)
addition, 2) aeration at modified pH, 3) C18 solid-phase extraction (SPE), and 4)
addition of Na2 S2 O3 . The results of the Santos TIE-I indicated toxicity by
sulfides and substances with affinity to C18 resin. In Bertioga, toxicity was the
result of NH3 , metals, and arsenic, as well as substances with affinity to C18
resin. Phase TIE-II aimed to specify the causes of toxicity by testing the
toxicity of eluates of the sublation and C18 SPE manipulation. The results
reinforced the role of both surfactants and nonpolar compounds as causative
agents of toxicity in both Santos and Bertioga. Chemical analyses of sediment
interstitial water or whole sediment ruled out the influence of polycyclic
aromatic hydrocarbons (PAHs) or polychlorinated biphenyls (PCBs) in the toxicity
of both sampling sites. Other hydrophobic substances may play a role in the
toxicity of Santos and Bertioga effluents. Efforts to remove such substances from
sanitary effluents must be prioritized. Environ Toxicol Chem 2017;36:1820-1832.
(c) 2017 SETAC.
PMID- 28401992
TI - "Operating without a firm knowledge of anatomy leads directly to increased
morbidity and mortality".
PMID- 28401991
TI - Supramolecular Amino Acid Based Hydrogels: Probing the Contribution of Additive
Molecules using NMR Spectroscopy.
AB - Supramolecular hydrogels are composed of self-assembled solid networks that
restrict the flow of water. l-Phenylalanine is the smallest molecule reported to
date to form gel networks in water, and it is of particular interest due to its
crystalline gel state. Single and multi-component hydrogels of l-phenylalanine
are used herein as model materials to develop an NMR-based analytical approach to
gain insight into the mechanisms of supramolecular gelation. Structure and
composition of the gel fibres were probed using PXRD, solid-state NMR experiments
and microscopic techniques. Solution-state NMR studies probed the properties of
free gelator molecules in an equilibrium with bound molecules. The dynamics of
exchange at the gel/solution interfaces was investigated further using high
resolution magic angle spinning (HR-MAS) and saturation transfer difference (STD)
NMR experiments. This approach allowed the identification of which additive
molecules contributed in modifying the material properties.
PMID- 28401993
TI - Synthesis of N-Propargylsulfoximines by Copper-Catalyzed A3 -Couplings.
AB - An efficient synthesis of N-propargylsulfoximines was developed through a copper
catalyzed coupling of aldehydes, alkynes, and NH-sulfoximines. The reaction
requires no co-catalyst or ligand and shows a wide substrate scope with moderate
to good yields.
PMID- 28401994
TI - Particulate matter chemical component concentrations and sources in settings of
household solid fuel use.
AB - Particulate matter (PM) air pollution derives from combustion and non-combustion
sources and consists of various chemical species that may differentially impact
human health and climate. Previous reviews of PM chemical component
concentrations and sources focus on high-income urban settings, which likely
differ from the low- and middle-income settings where solid fuel (ie, coal,
biomass) is commonly burned for cooking and heating. We aimed to summarize the
concentrations of PM chemical components and their contributing sources in
settings where solid fuel is burned. We searched the literature for studies that
reported PM component concentrations from homes, personal exposures, and direct
stove emissions under uncontrolled, real-world conditions. We calculated weighted
mean daily concentrations for select PM components and compared sources of PM
determined by source apportionment. Our search criteria yielded 48 studies
conducted in 12 countries. Weighted mean daily cooking area concentrations of
elemental carbon, organic carbon, and benzo(a)pyrene were 18.8 MUg m-3 , 74.0 MUg
m-3 , and 155 ng m-3 , respectively. Solid fuel combustion explained 29%-48% of
principal component/factor analysis variance and 41%-87% of PM mass determined by
positive matrix factorization. Multiple indoor and outdoor sources impacted PM
concentrations and composition in these settings, including solid fuel burning,
mobile emissions, dust, and solid waste burning.
PMID- 28401996
TI - Exploration and performance evaluation of microwave-induced plasma with different
discharge gases for ambient desorption/ionization mass spectrometry.
AB - RATIONALE: Microwave-induced plasma (MIP) with different discharge gases of argon
or helium provides significant plasma-based ambient desorption/ionization
sources, which have potential applicability in direct analysis of complex samples
without any sample pre-treatment. In this study, experiments were conducted to
better understand microwave-induced plasma desorption/ionization (MIPDI) sources
and the corresponding ionization mechanisms. METHODS: Emission spectra of
microwave-induced argon (MIP-Ar) and helium (MIP-He) plasmas were obtained from
the plasma tail flame of a MIP source. Compounds including L-phenylalanine, L
serine, L-valine, urea, 4-acetaminophen, gallic acid and L-ascorbic acid were
analyzed using both sources. Polyethylene glycol 400 (PEG400) oligomers were
detected by MIP-Ar and MIP-He mass spectrometry at different microwave powers.
Mass spectra of higher molecular weight PEGs (including PEG800, PEG1000 and
PEG2000) were also acquired using both sources. RESULTS: In the emission spectra,
N2 , H-I and O-I species were observed by MIP-Ar/He. In addition, SiO2 , Na-I, Si
I and Si-II species were generated by MIP-He. In the mass spectra of compounds,
[M+H]+ , [2M+H]+ , [M+O+H]+ , [M+2O-H]+ and fragment ions were observed. In the
mass spectra of PEG400 obtained by MIP-Ar/He at different microwave powers,
higher molecular weight oligomers could only be observed with higher microwave
power. PEGs with molecular weights as high as 1000 Da were also successfully
analyzed by MIPDI. CONCLUSIONS: According to the different natures of the
samples, either MIP-Ar or MIP-He can be chosen as a working ion source for mass
spectrometry. The MIPDI source is potentially applicable to the analysis of
compounds with high molecular weights, especially polymers with high degree of
polymerization (such as PEG2000), which is a challenging issue for the
traditional ambient ionization sources. Copyright (c) 2017 John Wiley & Sons,
Ltd.
PMID- 28401995
TI - Orthostatic dizziness in Parkinson's disease is attributed to cerebral
hypoperfusion: A transcranial doppler study.
AB - OBJECTIVES: Orthostatic hypotension (OH) is controversially regarded as the cause
of orthostatic dizziness in Parkinson's disease (PD). We sought to evaluate
whether cerebral autoregulation is an alternative cause for orthostatic dizziness
in PD patients, using transcranial Doppler monitoring during head-up tilting.
METHODS: Forty-five PD patients with dizziness, 13 PD patients without dizziness,
and 10 age-matched healthy controls were enrolled. Participants were divided into
the following four groups: patients with dizziness and OH (group 1, n = 22),
patients with dizziness but no OH (n = 23, group 2), patients without dizziness
(n = 11, group 3), and age-matched healthy controls (n = 10, group 4). All
participants underwent transcranial Doppler and blood pressure monitoring for 10
minutes during the head-up tilt test. Changes in the cerebral blood flow velocity
(CBFV) in the middle cerebral artery and the mean blood pressure (mBP) within 3
minutes after head-up tilting were compared between groups. RESULTS: Group 1
showed a significantly higher change in mBP (-16.3 +/- 10.8 mmHg) than groups 2 (
2.6 +/- 4.9), 3 (-2.2 +/- 3.6), or 4 (1.8 +/- 6.0) (p < 0.001). However, groups 3
(4.6 +/- 3.0 cm/s) and 4 (-4.2 +/- 2.5) showed a significantly smaller change in
CBFV than groups 1 (-9.0 +/- 4.2) and 2 (-8.1 +/- 5.1) (p < 0.01). CONCLUSIONS:
Our results suggest that cerebral hypoperfusion contributes to dizziness in PD
patients despite a lack of OH. Transcranial Doppler monitoring during head-up
tilting may be a useful tool for evaluating dizziness in PD patients with or
without OH. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:337-342, 2017.
PMID- 28401997
TI - Neuroprotective effects of phloretin and its glycosylated derivative on rotenone
induced toxicity in human SH-SY5Y neuronal-like cells.
AB - Phloretin and phlorizin are the two strong natural antioxidants whose biological
and pharmacological applications are rapidly growing in different human
pathological conditions. The neuroprotective activity of the two flavonoids has
been analyzed on cell culture of neuroblastoma cells. The neuroprotective
activity of the two flavonoids has been analyzed on cell culture of neuroblastoma
cells and evaluated by testing cell vitality, mitochondrial transmembrane
potential and ROS production, antioxidant enzymes detection, activation of
caspase 3, DNA damage, protein carbonylation, lipid peroxidation, and superoxide
anion scavenging activity. Incubation of cells with rotenone caused cell death
and significant increase in intracellular reactive oxygen species, activation of
caspase 3, and variation in mitochondrial transmembrane potential. Although,
rotenone exposure caused a significant increase of antioxidant enzymes, high
levels of lipid peroxidation were also observed. Phloretin or phlorizin, at
micromolar concentration, reduced rotenone-induced cell death by scavenging
ability against superoxide anion radical, one of the main effectors of rotenone
toxicity at level of mitochondrial respiratory chain complex I. Under our
experimental conditions, a reduction of the intracellular ROS levels with
consequent normalization of the aforementioned antioxidant enzymes occurred.
Concomitantly, we observed the inhibition of caspase 3 activity and DNA damage.
This study shows the promising neuroprotective ability of the two
dihydrochalcones able to protect human differentiated neuroblastoma cells
(commonly used as model of Parkinson's disease) from injury induced by rotenone,
actively scavenging ROS, normalizing mitochondrial transmembrane potential and
consequently avoiding energy depletion. (c) 2017 BioFactors, 43(4):549-557, 2017.
PMID- 28401999
TI - Effects of aflatoxin B1 on mitochondrial respiration, ROS generation and
apoptosis in broiler cardiomyocytes.
AB - Aflatoxin B1 (AFB1) develops various toxic effects in the liver by impairing
mitochondrial function, inducing cell apoptosis. However, little is focused on
its toxicity to broiler cardiomyocytes (BCMs). Here, the mitochondrial membrane
potential (MMP), reactive oxygen species (ROS) generation, cardiac troponin T
(cTnT) location, apoptosis induced by AFB1, and antioxidative genes were
investigated in BCMs. It was found that AFB1 evoked intracellular ROS generation,
and induced apoptosis in BCMs. AFB1 treatment resulted in increased percentage of
apoptotic cells, increased location range of cTnT in cytoplasm, upregulated
messenger RNA (mRNA) expression of nuclear factor erythroid 2-related factor 2
(Nrf2) and downregulated mRNA expressions of Mn-superoxide dismutase in BCMs.
These findings suggested AFB1 treatment caused significant cardiomyocyte damage
and cardiotoxicity, impairment of mitochondrial functions, activated ROS
generation, and induced apoptosis, and probably was involved in the Nrf2 signal
pathway in BCMs.
PMID- 28401998
TI - Early discontinuation of antiseizure medications in neonates with hypoxic
ischemic encephalopathy.
AB - OBJECTIVE: Neonates with hypoxic-ischemic encephalopathy (HIE) managed with
therapeutic hypothermia (TH) often experience acute symptomatic seizures,
prompting treatment with antiseizure medications (ASMs). Because the risk of
seizure occurrence after hospital discharge is unknown, the optimal ASM treatment
duration is unclear. We aimed to determine the risk of seizure occurrence after
hospital discharge and the impact of ASM treatment duration on this outcome.
METHODS: We performed a single-center, retrospective study of consecutive
neonates with HIE managed with TH who received ASMs for acute symptomatic
seizures from June 2010 through December 2014. Neonates were monitored with
continuous electroencephalography (EEG) during TH. RESULTS: Follow-up data were
available for 59 (82%) of 72 neonates who survived to discharge, with a median
follow-up period of 19 months (interquartile range [IQR] 11-25). Acute
symptomatic seizures occurred in 35 neonates (59%), including electrographic
seizures in 21 neonates (36%). ASMs were continued upon discharge in 17 (49%) of
35 neonates. Seizures occurred in follow-up in four neonates (11%). No patient
for whom ASMs were discontinued prior to discharge experienced seizures during
the follow-up period. SIGNIFICANCE: Among neonates with HIE, seizures after
hospital discharge were rare in those with acute symptomatic seizures and did not
occur in neonates without acute symptomatic seizures. ASM discontinuation prior
to discharge did not increase the risk of seizures during the follow-up period,
suggesting that ASMs may be discontinued in many neonates prior to discharge.
PMID- 28402000
TI - X chromosome drive in a widespread Palearctic woodland fly, Drosophila testacea.
AB - Selfish genes that bias their own transmission during meiosis can spread rapidly
in populations, even if they contribute negatively to the fitness of their host.
Driving X chromosomes provide a clear example of this type of selfish
propagation. These chromosomes have important evolutionary and ecological
consequences, and can be found in a broad range of taxa including plants, mammals
and insects. Here, we report a new case of X chromosome drive (X drive) in a
widespread woodland fly, Drosophila testacea. We show that males carrying the
driving X (SR males) sire 80-100% female offspring and possess a diagnostic X
chromosome haplotype that is perfectly associated with the sex ratio distortion
phenotype. We find that the majority of sons produced by SR males are sterile and
appear to lack a Y chromosome, suggesting that meiotic defects involving the Y
chromosome may underlie X drive in this species. Abnormalities in sperm cysts of
SR males reflect that some spermatids are failing to develop properly, confirming
that drive is acting during gametogenesis. By screening wild-caught flies using
progeny sex ratios and a diagnostic marker, we demonstrate that the driving X is
present in wild populations at a frequency of ~ 10% and that suppressors of drive
are segregating in the same population. The testacea species group appears to be
a hot spot for X drive, and D. testacea is a promising model to compare driving X
chromosomes in closely related species, some of which may even be younger than
the chromosomes themselves.
PMID- 28402001
TI - Synthesis, Structures, and Photophysical Properties of Alternating Donor-Acceptor
Cycloparaphenylenes.
AB - The synthesis of alternating donor-acceptor [12] and [16]cycloparaphenylenes
(CPPs) has been achieved by the rhodium-catalyzed intermolecular cross
cyclotrimerization followed by imidation and/or aromatization. These alternating
donor-acceptor CPPs showed positive solvatofluorochromic properties and smaller
HOMO-LUMO gaps compared with nonfunctionalized CPPs, which was confirmed by the
theoretical study.
PMID- 28402002
TI - Mental health and associated factors among young offenders in Chile: a cross
sectional study.
AB - BACKGROUND: Few studies in Latin America have explored mental disorder among
young offenders, or variables associated with it. AIMS: Our aim was to test for
associations between childhood adversity or substance misuse and psychiatric
disorders among young offenders. METHODS: Sentenced adolescent offenders were
recruited from young offenders' institutions or community centres provided by the
Chilean National Service for Minors. Psychiatric disorders were assessed using
the Mini International Neuropsychiatric Interview, conducted by trained
psychologists. A trained sociologist used an ad hoc interview to collect
information about childhood experiences, including parenting, trauma, education
and substance misuse. Multivariable logistic regressions were used to analyse
data. RESULTS: The most prevalent psychiatric disorders among the 935
participants were marijuana dependence disorder, major depressive disorder, and
anxiety disorders. Substance use disorders were less frequent among young
offenders who were serving their sentence in young offenders' institutions than
among those serving in community centres and more frequent among those who
started to use marijuana at an earlier age. Among other variables, childhood
maltreatment was related to major depressive disorder, and maternal death to
anxiety disorders. Higher educational status was related to a lower frequency of
depressive and anxiety disorders. CONCLUSIONS: Our findings suggest that greater
efforts must be made to identify vulnerable young people much earlier. Few of
these young offenders with mental health problems had been well adjusted in
health, education or socially before this period of detention. (c) 2017 The
Authors. Criminal Behaviour and Mental Health Published by John Wiley & Sons Ltd.
PMID- 28402003
TI - Bronchoalveolar lavage fluid in an infant with perinatal lethal Gaucher disease.
PMID- 28402004
TI - The VEGF gene polymorphism impacts brain volume and arterial blood volume.
AB - Vascular endothelial growth factor (VEGF) plays a critical role in the
angiogenesis and proliferation of various types of cells such as neurons,
astroglia, and endothelial cells in the brain. A common polymorphism in the VEGF
gene (-2578 C/A) is associated with circulating VEGF levels, cancers and
Alzheimer's disease. Nonetheless, the effects of this polymorphism on normal
human brain volume, arterial blood volume, and blood supply remain unclear. In
this study, the effects of this polymorphism on the total gray matter volume
(TGMV) and total white matter volume (TWMV) using T1-weighted structural images
and the total arterial blood volume (TABV) and mean cerebral blood flow (mCBF)
during rest using arterial spin labeling (ASL) in 765 young adult humans were
investigated. Voxel-by-voxel whole-brain analyses of these measures were also
performed. Multiple regression analyses with age and sex as covariates revealed
that the VEGF genotype (number of C alleles) was significantly and positively
correlated with TGMV, TWMV, and TABV as well as with regional gray and white
matter volumes in widespread areas and regional arterial blood volume in some
areas with high arterial blood volume. However, these regional associations were
not seen when the corresponding global signal was included as a covariate in the
multiple regression analyses, indicating that we failed to obtain evidence of
region-specific associations between these brain measures and the genotype. The
results suggest that the VEGF-2578C allele, is associated with changes in the
vascular system that lead to increased blood volume and larger brain volume. Hum
Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28402005
TI - Prevalence and risk factors for red blood cell alloimmunization in 175 children
with sickle cell disease in a French university hospital reference centre.
AB - Patients with sickle cell disease (SCD) show a high prevalence of red blood cell
(RBC) alloimmunization, but few studies have focused on children. We aimed to
study the prevalence and risk factors of RBC alloimmunization in SCD children. We
retrospectively analysed the medical and transfusion files for 245 SCD children
hospitalized in our centre in 2014 and included 175 patients who had received at
least one RBC unit in their lifetime. The main clinical and immuno-haematological
characteristics of alloimmunized and non-alloimmunized patients were compared.
The prevalence of alloimmunization was 13.7% [95% confidence interval (CI) (8.6
18.6)], and 7.4% [95% CI (3.5-11.3)] after excluding the probable irregular
natural antibodies (anti-M, anti-Lea , anti-Leb , anti-Lex ). Main risk factors
for alloimmunization were increased number of RBC units received (median of 65
vs. 10 units per patient; P = 0.01) and the presence of one or more red cell
autoantibodies (46.2% vs. 4.7%; P < 0.0001). The alloimmunization rate was higher
for episodically transfused than chronically transfused patients (1.43 vs.
0.24/100 units received; P < 0.001). The presence of red cell autoantibodies
appears to be a major risk factor for alloimmunization in SCD children and could
justify specific transfusion guidelines.
PMID- 28402006
TI - Virus myocarditis in a 1-month-old boy presenting as two types of paroxysmal
supraventricular tachycardia.
AB - Herein we describe the case of a 1-month-old boy with acute viral myocarditis,
who presented with two kinds of paroxysmal supraventricular tachycardia, and who
was cured after medical treatment. He was brought to the emergency room with poor
feeding due to fever. On the third day of hospitalization, a narrow QRS
tachycardia (180-200 beats/min) was detected. Echocardiography showed a high
echoic area at the atrial septum around the atrioventricular node. The patient
was clinically diagnosed with acute myocarditis. The narrow QRS tachycardia was
diagnosed as incessant junctional ectopic tachycardia. The patient was treated
with propranolol and landiolol. The frequency of the tachycardia decreased, but a
different narrow QRS tachycardia was detected on the 15th day of hospitalization
on electrocardiogram (220 beats/min), which was ascribed to atrioventricular
nodal re-entrant tachycardia. Atenolol was effective for the tachycardia. At 2
years follow up, cardiac function was normal and tachycardia had not recurred.
PMID- 28402007
TI - Interactions of bovine oocytes with follicular elements with respect to lipid
metabolism.
AB - Among many factors, lipid metabolism within the follicular environment emerges as
an important indicator of oocyte quality. In the literature a crucial
significance is described concerning follicular fluid (FF) composition as well as
messenger RNA (mRNA) expression in follicular cells. The aim of this study was to
describe the relationship between oocyte, FF and follicular cells with regard to
lipid metabolism. The set of data originating from individual follicles
comprised: lipid droplets (LD) number in oocytes (BODIPY staining), mRNA
expression of seven genes in cumulus and granulosa cells (SCD, FADS2, ELOVL2,
ELOVL5, GLUT1, GLUT3, GLUT8; real time polymerase chain reaction) and fatty acid
(FA) composition in FF (gas chromatography). Obtained results demonstrate
significant correlation between oocyte lipid droplets number and FA composition
in FF. However, gene expression studies show significant correlation between LD
number and GLUT1 gene only. Moreover, the present experiment revealed
correlations between FA content in FF and expression of several genes (SCD,
FADS2, ELOVL5, GLUT8) in granulosa cells, whereas only the SCD gene in cumulus
cells. We suggest that the results of our experiment indicate the importance of
glucose : lipid metabolism balance, which contributes to better understanding of
energy metabolism conversion between oocytes and the maternal environment.
PMID- 28402008
TI - Genome-wide association studies reveal additional related loci for fatty acid
composition in a Duroc pig multigenerational population.
AB - The aim of the present study was to detect quantitative trait loci affecting
fatty acid composition in back fat and intramuscular fat in a Duroc pig
population comprising seventh-generation pedigrees using genome-wide association
studies (GWAS). In total, 305 animals were genotyped using single nucleotide
polymorphisms (SNPs) array and five selected SNPs from regions containing known
candidate genes related to fatty acid synthesis or metabolism. In total, 24
genome-wide significant SNP regions were detected in 12 traits, and 76 genome
wide suggestive SNP regions were detected in 33 traits. The Sus scrofa chromosome
(SSC) 7 at 10.3 Mb was significantly associated with C17:0 in intramuscular fat,
while the SSC9 at 13.6 Mb was significantly associated with C14:0 in
intramuscular fat. The SSC12 at 1.0 Mb was significantly associated with C14:0 in
back fat and the SSC14 at 121.0 Mb was significantly associated with C18:0 in
intramuscular fat. These regions not only replicated previously reported loci
containing some candidate genes involved in fatty acid composition (fatty acid
synthase and stearoyl-CoA desaturase) but also included several additional
related loci.
PMID- 28402009
TI - Genetic relationships between temperament of calves at auction and carcass traits
in Japanese Black cattle.
AB - Correlations of calves' temperament with carcass traits were estimated to clarify
the genetic relationships between them in Japanese Black cattle. The temperament
records for 3128 calves during auction at a calf market were scored on a scale of
1 (calm) to 5 (nervous) as temperament score (TS), and the TS were divided into
two groups (TSG): TS 1 and 2 comprised TSG 1, and 3 to 5 constituted TSG 2.
Carcass data were obtained from 33 552 fattened cattle. A threshold animal model
was used for analyzing the underlying liability for TSG, whereas a linear one was
used for TS and carcass traits. The heritability estimates for TS and TSG were
0.12 and 0.11, respectively. On the other hand, moderate to high heritability
estimates were obtained for carcass traits (0.40 to 0.68). The temperament scores
were negatively correlated with carcass weight, rib thickness and subcutaneous
fat thickness (-0.13 to -0.59). In contrast, weak to moderate positive
correlations were found between the temperament scores and rib eye area or yield
estimate (0.16 to 0.45). The temperament scores and beef marbling score had no
correlation. These results showed that it is possible to improve temperament and
carcass traits simultaneously.
PMID- 28402010
TI - Shape-Shifting Patchy Particles.
AB - A facile method to synthesize shape-shifting patchy particles on the colloidal
scale is described. The design is based on the solvent-induced shifting of the
patch shape between concave and convex features. The initial concave patchy
particles were synthesized in a water suspension by a swelling-induced buckling
process. Upon exposure to different solvents, the patches were tuned reversibly
to be either concave or convex. These particles can be assembled into chained,
branched, zigzag, and cyclic colloidal superstructures in a highly site-specific
manner by surface-liquid capillary bridging. The biphasic nature of the particles
also enables site-selective surface functionalization.
PMID- 28402012
TI - Stable NiII Porphyrin meso-Oxy Radical with a Quartet Ground State.
AB - 10,15,20-Tris(pentafluorophenyl)-substituted NiII -porphyrin meso-oxy radical
bearing two coordinating pyridines was synthesized as a stable radical with a
quartet ground state (S=3/2). X-ray structural analysis revealed that the NiII
porphyrin moiety is fairly planar and the Ni-N bond lengths are considerably
longer, indicating the high-spin state of the NiII center. The radical exhibited
a quartet ground state, indicating the ferromagnetic interaction between the high
spin NiII center (S=1) and the porphyrin meso-oxy radical (S=1/2).
PMID- 28402013
TI - The relevance of context in understanding health literacy skills: Findings from a
qualitative study.
AB - BACKGROUND: Conceptualizing health literacy as a relational concept, which
involves how individuals interact with complex health and social systems,
requires a greater understanding of the context of people's health experiences.
OBJECTIVES: To describe individuals' experiences of accessing, understanding,
appraising and applying health information; explore the barriers and facilitators
to using these skills; and to describe the experience of information exchange in
health consultations. DESIGN: A longitudinal qualitative methodology with
thematic analysis of interviews was used. Health literacy levels were assessed
using the HLS-EU-47-Item Questionnaire. Findings are presented from the first
round of data collection. SETTING AND PARTICIPANTS: Twenty-six participants
purposefully selected from a CVD risk reduction programme at three separate time
points. RESULTS: Four key themes identified: using health literacy capacities for
managing health; psychological and structural factors that impact on these
capacities; and the relationship quality with the health-care provider (HCP).
Although limited health literacy was prevalent across the sample (65%), all
individuals were very proactive in attempting to utilize health literacy skills.
Findings emphasize the importance of contextual factors such as the quality of
communication with the health-care provider, perceptions of control, attitudes to
family medical history, navigating structural barriers and being supported in
managing treatment and medication side-effects. DISCUSSION AND CONCLUSION:
Findings are relevant for health-care providers in order to enhance the patient
provider relationship and to ensure optimum health outcomes for all individuals
regardless of health literacy levels.
PMID- 28402014
TI - Advanced treatment technique for swine wastewater using two agents: Thermally
polymerized amorphous silica and hydrated lime for color and phosphorus removal
and sulfur for nitrogen removal.
AB - The efficacy of advanced treatment of swine wastewater using thermally
polymerized, modified amorphous silica and hydrated lime (M-CSH-lime) for color
and phosphorus removal and sulfur for nitrogen removal was examined with a
demonstration-scale treatment plant. The color removal rate was approximately 78%
at M-CSH-lime addition rates of > 0.055 wt/v%. The PO43--P removal rate exceeded
99.9% with > 0.023 wt/v%. pH of the effluent from the M-CSH-lime reactor
increased with the addition rate till a maximum value of 12.7, which was
effective in disinfection. The recovered M-CSH-lime would be suitable as a
phosphorus fertilizer because the total P2 O5 content was approximately 10%. The
nitrogen oxide (NOx-N) removal rate by sulfur denitrification increased to
approximately 80% when the NOx-N loading rate was around 0.1 kg-N/ton-S/day. It
was suggested that the combination of the two processes would be effective in the
advanced treatment of swine wastewater.
PMID- 28402015
TI - Synthesis and Bowl-in-Bowl Assembly of a Geodesic Phenylene Bowl.
AB - A phenylene multiring with a corannulenoidal skeleton was synthesized. Geodesic
constraints over 20 phenylene panels resulted in its nanometer-sized, bowl-shaped
molecular structure, which was unequivocally revealed by crystallographic
analysis. The crystal structure also showed the presence of a bowl-in-bowl
dimeric assembly, which was driven by entropic factors in solution.
PMID- 28402016
TI - A Vicinal Electrophilic Diborylation Reaction Furnishes Doubly Boron-Doped
Polycyclic Aromatic Hydrocarbons.
AB - Ten examples of unsymmetrically benzannulated, boron-doped polycyclic aromatic
hydrocarbons (B-PAHs) were prepared by a one-pot protocol using 4,5-dichloro-1,2
bis(trimethylsilyl)benzene (1), BBr3 , and selected PAHs-among them anthracene,
benzo[a]pyrene, biphenylene, and fluoranthene. After mesitylation at the boron
centers, the resulting air- and water-stable products were investigated by 1 H/11
B{1 H}/13 C{1 H} NMR spectroscopy, X-ray crystallography, cyclic voltammetry, and
UV/Vis absorption/emission spectroscopy. The experiments were augmented by DFT
calculations. Most of the B-PAHs are brightly luminescent (PhiPL up to 90 %) and
undergo reversible reduction at moderate half-wave potentials. The two chloro
substituents of 1 are not only mandatory for accomplishing efficient
diborylation, but can subsequently be used for Stille-type coupling reactions to
introduce 2-thienyl moieties. Alternatively, Cl/H exchange is achievable with
HSiEt3 in a quantitative, Pd-catalyzed transformation.
PMID- 28402017
TI - Asthma education for school staff.
AB - BACKGROUND: Teachers and school staff should be competent in managing asthma in
schools. Demonstrated low levels of asthma knowledge mean that staff may not know
how best to protect a child with asthma in their care, or may fail to take
appropriate action in the event of a serious attack. Education about asthma could
help to improve this knowledge and lead to better asthma outcomes for children.
OBJECTIVES: To assess the effectiveness and safety of asthma education programmes
for school staff, and to identify content and attributes underpinning them.
SEARCH METHODS: We conducted the most recent searches on 29 November 2016.
SELECTION CRITERIA: We included randomised controlled trials comparing an
intervention to educate school staff about asthma versus a control group. We
included studies reported as full text, those published as abstract only and
unpublished data. DATA COLLECTION AND ANALYSIS: At least two review authors
screened the searches, extracted outcome data and intervention characteristics
from included studies and assessed risk of bias. Primary outcomes for the
quantitative synthesis were emergency department (ED) or hospital visits,
mortality and asthma control; we graded the main results and presented evidence
in a 'Summary of findings' table. We planned a qualitative synthesis of
intervention characteristics, but study authors were unable to provide the
necessary information.We analysed dichotomous data as odds ratios, and continuous
data as mean differences or standardised mean differences, all with a random
effects model. We assessed clinical, methodological and statistical heterogeneity
when performing meta-analyses, and we narratively described skewed data. MAIN
RESULTS: Five cluster-RCTs of 111 schools met the review eligibility criteria.
Investigators measured outcomes in participating staff and often in children or
parents, most often at between 1 and 12 months.All interventions were educational
programmes but duration, content and delivery varied; some involved elements of
training for pupils or primary care providers. We noted risk of selection,
performance, detection and attrition biases, although to a differing extent
across studies and outcomes.Quanitative and qualitative analyses were limited.
Only one study reported visits to the ED or hospital and provided data that were
too skewed for analysis. No studies reported any deaths or adverse events.
Studies did not report asthma control consistently, but results showed no
difference between groups on the paediatric asthma quality of life questionnaire
(mean difference (MD) 0.14, 95% confidence interval (CI) -0.03 to 0.31; 1005
participants; we downgraded the quality of evidence to low for risk of bias and
indirectness). Data for symptom days, night-time awakenings, restricted
activities of daily living and school absences were skewed or could not be
analysed; some mean scores were better in the trained group, but most differences
between groups were small and did not persist to 24 months.Schools that received
asthma education were more adherent to asthma policies, and staff were better
prepared; more schools that had received staff asthma training had written asthma
policies compared with control schools, more intervention schools showed
improvement in measures taken to prevent or manage exercise-induced asthma
attacks and more staff at intervention schools reported that they felt able to
administer salbutamol via a spacer. However, the quality of the evidence was low;
results show imbalances at baseline, and confidence in the evidence was limited
by risk of bias and imprecision. Staff knowledge was higher in groups that had
received asthma education, although results were inconsistent and difficult to
interpret owing to differences between scales (low quality).Available information
about the interventions was insufficient for review authors to conduct a
meaningful qualitative synthesis of the content that led to a successful
intervention, or of the resources required to replicate results accurately.
AUTHORS' CONCLUSIONS: Asthma education for school staff increases asthma
knowledge and preparedness, but studies vary and all available evidence is of low
quality. Studies have not yet captured whether this improvement in knowledge has
led to appreciable benefits over the short term or the longer term for the safety
and health of children with asthma in school. Randomised evidence does not
contribute to our knowledge of content or attributes of interventions that lead
to the best outcomes, or of resources required for successful
implementation.Complete reporting of the content and resources of educational
interventions is essential for assessment of their effectiveness and feasibility
for implementation. This applies to both randomised and non-randomised studies,
although the latter may be better placed to observe important clinical outcomes
such as exacerbations and mortality in the longer term.
PMID- 28402018
TI - Phloretin attenuates hyperuricemia-induced endothelial dysfunction through co
inhibiting inflammation and GLUT9-mediated uric acid uptake.
AB - Hyperuricemia is an important risk factor for cardiovascular and renal diseases.
Phloretin had shown antioxidant and anti-inflammatory properties, but its role in
endothelial injury is rarely reported. In this study, we aimed to investigate the
protective effect of phloretin on UA-induced injury in human umbilical vein
endothelial cells. The effects of UA and phloretin on cell viability,
inflammation, THP-1 monocyte adhesion, endothelial cell tube formation, GLUT9
expression and UA uptake in human umbilical vein endothelial cells were
evaluated. The changes of nuclear factor-kappa B/extracellular regulated protein
kinases signalling were also analysed. Our results showed that UA reduced cell
viability and tube formation, and increased inflammation and monocytes adhesion
in human umbilical vein endothelial cells in a dose-dependent manner. In
contrast, phloretin significantly attenuated pro-inflammatory factors expression
and endothelial injury induced by UA. Phloretin inhibited the activation of
extracellular regulated protein kinases/nuclear factor-kappa B pathway, and
reduced GLUT9 and it mediated UA uptake in human umbilical vein endothelial
cells. These results indicated that phloretin attenuated UA-induced endothelial
injury via a synergic mechanism including direct anti-inflammatory effect and
lowering cellular UA uptake. Our study suggested that phloretin might be a
promising therapy for hyperuricemia-related cardiovascular diseases.
PMID- 28402020
TI - Synthesis of Aromatic Sulfones from SO2 and Organosilanes Under Metal-free
Conditions.
AB - The conversion of SO2 into arylsulfones under metal-free conditions was achieved
for the first time by reacting SO2 with (hetero)arylsilanes and alkylhalides in
the presence of a fluoride source. The mechanism of this transformation was
elucidated based on DFT calculations, which highlight the influence of SO2 in
promoting C-Si bond cleavage.
PMID- 28402019
TI - Epigallocatechin gallate inhibits Streptococcus pneumoniae virulence by
simultaneously targeting pneumolysin and sortase A.
AB - Streptococcus pneumoniae (pneumococcus), the causative agent of several human
diseases, possesses numerous virulence factors associated with pneumococcal
infection and pathogenesis. Pneumolysin (PLY), an important virulence factor, is
a member of the cholesterol-dependent cytolysin family and has cytolytic
activity. Sortase A (SrtA), another crucial pneumococcal virulence determinate,
contributes greatly to the anchoring of many virulence-associated surface
proteins to the cell wall. In this study, epigallocatechin gallate (EGCG), a
natural compound with little known antipneumococcal activity, was shown to
directly inhibit PLY-mediated haemolysis and cytolysis by blocking the
oligomerization of PLY and simultaneously reduce the peptidase activity of SrtA.
The biofilm formation, production of neuraminidase A (NanA, the pneumococcal
surface protein anchored by SrtA), and bacterial adhesion to human epithelial
cells (Hep2) were inhibited effectively when S. pneumoniae D39 was cocultured
with EGCG. The results from molecular dynamics simulations and mutational
analysis confirmed the interaction of EGCG with PLY and SrtA, and EGCG binds to
Glu277, Tyr358, and Arg359 in PLY and Thr169, Lys171, and Phe239 in SrtA. In vivo
studies further demonstrated that EGCG protected mice against S. pneumoniae
pneumonia. Our results imply that EGCG is an effective inhibitor of both PLY and
SrtA and that an antivirulence strategy that directly targets PLY and SrtA using
EGCG is a promising therapeutic option for S. pneumoniae pneumonia.
PMID- 28402021
TI - Validation of non-invasive haemodynamic methods in patients with liver disease:
the Finometer and the Task Force Monitor.
AB - Patients with advanced cirrhosis often present a hyperdynamic circulation
characterized by a decrease in systolic and diastolic blood pressure (SBP and
DBP), and an increase in heart rate (HR) and cardiac output (CO). Accurate
assessment of the altered circulation can be performed invasively; however, due
to the disadvantages of this approach, non-invasive methods are warranted. The
purpose of this study was to compare continuous non-invasive measurements of
haemodynamic variables by the Finometer and the Task Force Monitor with
simultaneous invasive measurements. In 25 patients with cirrhosis, SBP, DBP and
HR were measured non-invasively and by femoral artery catheterization. CO was
measured non-invasively and by indicator dilution technique. The non-invasive
pressure monitoring was considered acceptable with a bias (accuracy) and a SD
(precision) not exceeding 5 and 8 mmHg, respectively, as recommended by the
Association for the Advancement of Medical Instrumentation. The accuracy and
precision of the Finometer and the Task Force Monitor were as follows: SBP: -3.6
+/- 17.9 and -8.9 +/- 17.5 mmHg, respectively; DBP: 4.2 +/- 9.6 and 1.9 +/- 8.6
mmHg, respectively; HR: 2.0 +/- 6.9 and 2.2 +/- 6.2 bpm, respectively; and CO:
0.1 +/- 1.6 and -1.0 +/- 2.0 L min-1 , respectively. The study demonstrates that
the overall performances of the Finometer and the Task Force Monitor in
estimating absolute values of SBP, DBP, HR and CO in patients with cirrhosis are
not equivalent to the gold standard, but may have an acceptable performance with
repeated measurements.
PMID- 28402022
TI - Steroidogenic Acute Regulatory Protein (StAR) Overexpression Reduces Inflammation
and Insulin Resistance in Obese Mice.
AB - Steroidogenic acute regulatory protein (StAR), a mitochondrial cholesterol
delivery protein, plays a beneficial role in hyperlipidemia, NAFLD, and
endothelial inflammation. Elevated circulating fatty acids and low grade
inflammation are known as key risk factors of insulin resistance and type 2
diabetes. In the present study, C57BL/6J mice were fed with HFD and infected with
recombinant adenovirus expressing StAR by tail-vein injection. Intraperitoneal
glucose/insulin tolerance test was performed to assess the insulin sensitivity.
Morphological analysis and intramuscular lipid determination were used to
illustrate the adipose hypertrophy and ectopic fat accumulation in skeletal
muscle. The levels of inflammatory factor and nitric oxide were determined by
ELISA and classic Griess reagent methods, respectively. The fatty acids
composition was analysis using gas chromatography-mass spectrometry (GC-MS). The
expression of genes associated with inflammation and insulin resistance were
determined by Western blotting and qPCR to elucidate the underlying mechanism. We
demonstrated that StAR overexpression ameliorated insulin resistance and systemic
inflammatory response with the reduction of adipose hypertrophy and intramuscular
lipid in HFD-fed mice. In addition, StAR overexpression increased serum
unsaturated fatty acids (UFAs) and PPARgamma expression in muscle and adipose
tissue of obese mice. In conclusion, StAR may activate PPARgamma by increasing
UFAs, which leads to a protective role in systemic inflammation and insulin
resistance in obese mice. J. Cell. Biochem. 118: 3932-3942, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28402023
TI - Heart rate recovery improvement in patients following acute myocardial
infarction: exercise training, beta-blocker therapy or both.
AB - Heart rate recovery (HRR) is a strong mortality predictor. Exercise training (ET)
and beta-blocker therapy have significant impact on the HRR of patients following
myocardial infarction (MI). However, the combination of ET and beta-blocker
therapy, as well as its effectiveness in patients with a more compromised HRR
(<=12 bpm), has been under-studied. Male patients (n = 64) post-MI were divided:
Training + beta-blocker (n = 19), Training (n = 15), beta-blocker (n = 11) and
Control (n = 19). Participants performed an ergometric test before and after 3
months of intervention. HRR was obtained during 5 min of recovery and corrected
by the cardiac reserve (HRRcorrCR ). Compared to pre-intervention, HRRcorrCR was
significantly increased during the 1st and 2nd minutes of recovery in the
Training + beta-blocker group (70.5% and 37.5%, respectively; P<0.05). A
significant improvement, lasting from the 1st to the 4th minute of recovery, was
also observed in the Training group (47%, 50%, 25% and 8.7%, respectively;
P<0.05). In contrast, the beta-blocker group showed a reduction in HRRcorrCR
during the 2nd and 3rd minutes of recovery (-21.2% and -16.3%, respectively;
P<0.05). In addition, interventions involving ET (Training + betab, Training)
were significantly more effective in patients with a pre-intervention HRR <= 12
bpm than for patients with HRR > 12 bpm. Combination of beta-blocker therapy with
ET does not compromise the effect of training and instead promotes HRR and
aerobic capacity improvement. In addition, this combination is particularly
beneficial for individuals presenting with a more compromised HRR. However,
chronic administration of beta-blocker therapy alone did not promote improvement
in HRR or aerobic capacity.
PMID- 28402024
TI - Marburg virus-like particles produced in insect cells induce neutralizing
antibodies in rhesus macaques.
AB - Marburg virus (MARV), which is one of the most virulent agents in the world,
causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a
mortality rate of up to 90%. Currently, there is no effective treatment or
approved vaccine for MARV for human use to control disease outbreak and spread.
Virus-like particles (VLPs), which are morphologically identical to the native
infectious virus particle, are efficacious as vaccines against many viruses,
including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and
hepatitis B virus (HBV). In this study, we generated MARV virus-like particles
(VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the
baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed
with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG
titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320.
MARV VLPs also elicited interferon-gamma (IFN-gamma) and interleukin-4 (IL-4)
secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)
mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays.
These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent
immunogenicity in rhesus macaques and may be a promising candidate vaccine
against MARV.
PMID- 28402025
TI - A Fully Phosphane-Substituted Disilene.
AB - There is growing interest in compounds containing functionalized E=E multiple
bonds (E=Si, Ge, Sn, Pb) because of their potential to exhibit novel physical and
chemical properties. However, compounds containing multiple functionalizations
are rare, with scarcity increasing with increasing degree of substitution. The
first ditetrelene R2 E=ER2 in which the E=E bond is substituted by four
heteroatoms (other than Si) is described. The tetraphosphadisilene {(Mes)2 P}2
Si=Si{P(Mes)2 }2 (7) is readily isolated from the reaction between SiBr4 and
[(Mes)2 P]Li, the latter of which acts as a sacrificial reducing agent. The
structure of 7 is presented, while the bonding in, and stability of 7 were probed
using DFT calculations.
PMID- 28402026
TI - Influence of riders' skill on plasma cortisol levels of horses walking on forest
and field trekking courses.
AB - The aim of this study was to evaluate the influence of rider's skill on the
plasma cortisol levels of trekking horses on two courses, walking on field and
forest courses (about 4.5 to 5.1 km each). Three riders of different skills did
horse trekking (HT) in a tandem line under a fixed order: advanced-leading,
beginner-second and intermediate-last. A total of six horses were used and they
experienced all positions in both courses; a total of 12 experiments were done.
Blood samples were obtained before HT, immediately after and 2 h after HT. As a
control, additional blood samples were obtained from the same horses on non
riding days. Irrespective of the course and the rider's skill, the cortisol level
before HT was higher than that of control (P < 0.05). In both courses, the
cortisol levels immediately after HT ridden by the advanced rider were higher
than that of control (P < 0.05). However, in every case, the cortisol level 2 h
after HT was closely similar to the level of the control. Thus, we concluded the
stress of trekking horse was not sufficient to disturb the circadian rhythm of
the cortisol level, irrespective of the course and the rider's skill.
PMID- 28402027
TI - Simultaneous determination of difenoconazole, trifloxystrobin and its metabolite
trifloxystrobin acid residues in watermelon under field conditions by GC-MS/MS.
AB - An optimized quick, easy, cheap, effective, rugged and safe method for the
simultaneous determination of difenoconazole, trifloxystrobin and its metabolite
trifloxystrobin acid residues in watermelon and soil was developed and validated
by gas chromatography with tandem mass spectrometry. The samples were extracted
with acetonitrile (1% formic acid) and cleaned up by dispersive solid-phase
extraction with octadecylsilane sorbent. The limit of quantification of the
method was 0.01 mg/kg, and the limit of detection was 0.003 mg/kg for all three
analytes. The recoveries of the fungicides in watermelon, pulp and soil were
72.32-99.20% for difenoconazole, 74.68-87.72% for trifloxystrobin and 78.59
92.66% for trifloxystrobin acid with relative standard deviations of 1.34-14.04%.
The dissipation dynamics of difenoconazole and trifloxystrobin in watermelon and
soil followed the first-order kinetics with half-lives of 3.2-8.8 days in both
locations. The final residue levels of difenoconazole and trifloxystrobin were
below 0.1 mg/kg (maximum residue level [MRL] set by China) and 0.2 mg/kg (MRL set
by European Union), respectively, in pulp samples collected 14 days after the
last application. These results could help Chinese authorities to establish MRL
of trifloxystrobin in watermelon and provide guidance for the safe and proper
application of both fungicides on watermelon.
PMID- 28402028
TI - Ten guiding principles for youth mental health services.
AB - AIMS: Guiding principles are arguably central to the development of any health
service. The aim of this article is to report on the outcomes of a youth mental
health (YMH) community of practice (CoP), which identified a range of guiding
principles that provide a clear point of comparison for the only other set of
principles for YMH service delivery proposed to date. METHODS: A YMH CoP was
established in 2010 as part of the Victorian State Government approach to
improving YMH care. An initial literature search was undertaken to locate
articles on YMH service delivery. A number of common themes were identified,
which the YMH community of practice (YMHCoP) members then elaborated upon by
drawing from their collective experience of the YMH sector. The resultant themes
were then refined through subsequent group discussions to derive a definitive set
of guiding principles. These principles were then augmented by a second
literature search conducted in July 2015. RESULTS: Fifteen key themes were
derived from the initial literature search and YMH CoP discussions. These were
refined by the YMH CoP to produce 10 guiding principles for YMH service
development. These are discussed through reference to the relevant literature,
using the only other article on principles of YMH service delivery as a notable
point of comparison. CONCLUSION: The 10 principles identified may be useful for
quality improvement and are likely to have international relevance. We suggest
the timely pursuit of an international consensus on guiding principles for
service delivery under the auspices of a peak body for YMH.
PMID- 28402029
TI - Magnetic solid-phase extraction based on carbon nanotubes for the determination
of polyether antibiotic and s-triazine drug residues in animal food with LC
MS/MS.
AB - Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide
nanoparticles and carbon nanotubes, were prepared through a simple one-step
synthesis method and subsequently applied to magnetic solid-phase extraction for
the determination of polyether antibiotic and s-triazine drug residues in animal
food coupled with liquid chromatography with tandem mass spectrometry. The
nanocomposites were characterized by transmission electron microscopy, X-ray
diffraction, and vibrating sample magnetometry. The components within the
nanocomposites endowed the material with high extraction performance and
manipulative convenience. Compared with carbon nanotubes, the as-prepared carbon
nanotubes-magnetic nanoparticles showed better extraction and separation
efficiencies for polyether antibiotics and s-triazine drugs thanks to the
contribution of the iron-containing magnetic nanoparticles. Various experimental
parameters affecting the extraction efficiency had been investigated in detail.
Under the optimal conditions, the good linearity ranging from 1 to 200 MUg/kg for
diclazuril, toltrazuril, toltrazuril sulfone, lasalocid, monensin, salinomycin,
narasin, nanchangmycin, and maduramicin, low limits of detection ranging from 1
to 5 MUg/kg, and satisfactory spiked recoveries (77.1-91.2%, with the inter
relative standard deviation values from 4.0 to 12.2%) were shown. It was
confirmed that this novel method was an efficient pretreatment and enrichment
procedure and could be successfully applied for extraction and determination of
polyether and s-triazine drug residues in complex matrices.
PMID- 28402030
TI - Cyclic peptide *CRRETAWAC* attenuates fibronectin-induced cytokine secretion of
human airway smooth muscle cells by inhibiting FAK and p38 MAPK.
AB - alpha5beta1 integrin is highly expressed in airway smooth muscle cells and
mediate the adhesion of airway smooth muscle cells to fibronectin to regulate
airway remodelling in asthma. This study aimed to investigate the effects of
synthetic cyclic peptide *CRRETAWAC* on fibronectin-induced cytokine secretion of
airway smooth muscle cells and the underlying mechanism. Human airway smooth
muscle cells were isolated and treated with fibronectin, IL-13, *CRRETAWAC*
peptide, alpha5beta1 integrin-blocking antibody, FAK inhibitor or p38 MAPK
inhibitor. The transcription and secretion of eotaxin-1 and RANTES were detected
by real-time PCR and ELISA, respectively. The phosphorylation of FAK and MAPKs
including p38, ERK1/2 and JNK1/2 was detected by Western blot analysis. The
transcription and secretion of eotaxin-1 and RANTES increased in airway smooth
muscle cells cultured in fibronectin-coated plates. However, alpha5beta1 integrin
blocking antibody, *CRRETAWAC* peptide, FAK inhibitor or p38 MAPK inhibitor
significantly reduced mRNA levels and the secretion of eotaxin-1 and RANTES in
airway smooth muscle cells cultured in fibronectin-coated plates. In addition,
the phosphorylation of FAK and p38 MAPK was significantly increased in airway
smooth muscle cells cultured in fibronectin-coated plates compared to the cells
cultured in uncoated plates and was significantly reduced in airway smooth muscle
cells treated with *CRRETAWAC* peptide. Fibronectin induces cytokine synthesis
and secretion of airway smooth muscle cells. Peptide *CRRETAWAC* antagonizes
fibronectin-induced cytokine synthesis and secretion of airway smooth muscle
cells via the inhibition of FAK and p38 MAPK, and is a potential agent for the
therapy of asthma.
PMID- 28402031
TI - Evaluation of osseous-associated cervical spondylomyelopathy in dogs using
kinematic magnetic resonance imaging.
AB - Osseous-associated cervical spondylomyelopathy in dogs is characterized by both
static and dynamic spinal cord compression; however, standard MRI methods only
assess static compression. In humans with cervical spondylotic myelopathy,
kinematic MRI is commonly used to diagnose dynamic spinal cord compressions. The
purpose of this prospective, analytical study was to evaluate kinematic MRI as a
method for characterizing the dynamic component of osseous-associated cervical
spondylomyelopathy in dogs. We hypothesized that kinematic MRI would allow
visualization of spinal cord compressions that were not identified with standard
imaging. Twelve client-owned dogs with osseous-associated cervical
spondylomyelopathy were enrolled. After standard MRI confirmed a diagnosis of
osseous-associated cervical spondylomyelopathy, a positioning device was used to
perform additional MRI sequences with the cervical vertebral column flexed and
extended. Morphologic and morphometric (spinal cord height, intervertebral disc
width, spinal cord width, vertebral canal height, and spinal cord area)
assessments were recorded for images acquired with neutral, flexion, and
extension imaging. A total of 25 compressions were seen with neutral positioning,
while extension identified 32 compressions. There was a significant association
between extension positioning and presence of a compressive lesion at C4-C5 (p =
0.02). Extension was also associated with a change in the most severe site of
compression in four out of 12 (33%) dogs. None of the patients deteriorated
neurologically after kinematic imaging. We concluded that kinematic MRI is a
feasible method for evaluating dogs with osseous-associated cervical
spondylomyelopathy, and can reveal new compressions not seen with neutral
positioning.
PMID- 28402032
TI - Furosemide loading test in a case of homozygous solute carrier family 12, member
1 (SLC12A1) mutation (g.62382825G>A, p.Pro372Leu) in Japanese Black cattle.
AB - Hydrallantois is the excessive accumulation of fluid in the allantoic cavity in a
pregnant animal and is associated with fetal death. We recently identified a
recessive missense mutation in the solute carrier family 12, member 1 (SLC12A1)
gene (g.62382825G>A, p.Pro372Leu) that is associated with hydrallantois in
Japanese Black cattle. Unexpectedly, we found a case of the homozygous risk
allele for SLC12A1 in a calf, using a PCR-based direct DNA sequencing test. The
homozygote was outwardly healthy up to 3 months of age and the mother did not
exhibit any clinical symptoms of hydrallantois. In order to validate these
observations, we performed confirmation tests for the genotype and a diuretic
loading test using furosemide, which inhibits the transporter activity of the
SLC12A1 protein. The results showed that the calf was really homozygous for the
risk-allele. In the homozygous calf, administration of furosemide did not alter
urinary Na+ or Cl- levels, in contrast to the heterozygote and wild-type calves
in which these were significantly increased. These results demonstrate that the
SLC12A1 (g.62382825G>A, p.Pro372Leu) is a hypomorphic or loss-of-function
mutation and the hydrallantois with this mutation shows incomplete penetrance in
Japanese Black cattle.
PMID- 28402033
TI - Metabolic syndrome in antipsychotic naive African patients with severe mental
illness in usual care.
AB - BACKGROUND: To determine the prevalence and incidence of metabolic syndrome in
individuals with a first episode of severe mental illness from South Africa.
METHODS: Antipsychotic naive study subjects with a first episode of severe mental
illness and control subjects were recruited at baseline for a prospective study.
Individuals without metabolic syndrome at baseline were followed up for 12 months
after antipsychotic medication was initiated. Metabolic syndrome was determined
at baseline and at the 12-month follow-up using the Joint Interim Statement
criteria. RESULTS: At baseline, the 67 study (M:F; 48:19) and 67 control subjects
(M:F; 48:19) had a mean age of 22.8 (+/-3.7) and 23.3 (+/-2.6) years (P = .4),
respectively. The majority were of black African ethnicity (97%) and 82% were
diagnosed with schizophrenia. There was no difference in the prevalence of
metabolic syndrome (4.5%) or any of the individual components between the study
and control group prior to the initiation of antipsychotics. Of the 64 study
subjects without metabolic syndrome at baseline, only 36 (M:F; 25:11) completed
the 12-month follow-up (response rate 56.3%) and 2 subjects developed metabolic
syndrome .The incidence of metabolic syndrome was 5.5% with a significant
increase in the elevated waist circumference criterion after 1 year of
antipsychotic treatment (P = .02). CONCLUSIONS: There was a low prevalence and
incidence of metabolic syndrome in this group of patients with a first episode of
severe mental illness.
PMID- 28402034
TI - Measurement of blood pressure to detect elusive kidney disease.
PMID- 28402035
TI - Screening and investigation Lactobacillius spp. to improve Secale cereale silage
quality.
AB - Silage is a high-moisture-content forage that is used to feed livestock. Using
silage as feed is economically feasible and suitable for cattle management.
Secale cereale is considered as a high-quality forage plant. After the heading
stage the biomass of S. cereale increases by up to 30%; however, lignification in
the cell wall causes low fermentation efficiency and coefficient digestibility,
and it may also be contaminated by mycotoxin-producing fungi and can impair the
quality of the silage. Therefore, the aim of this study was to screen beneficial
Lactobacillius spp. for S. cereale silage to reduce fungi contamination and to
increase fibrinolytic ability in the silage. Up to 100 days fermentation period
and total 180 lactic acid bacteria were isolated and only a single isolate, R4
26, showed strong acidification ability and antifungal activities against
mycotoxin-producing fungus. According to quantitative RT-PCR results, the
mycotoxin-producing fungal contamination was significantly reduced in the S.
cereale silage containing the R4-26 isolate. In enzymatic assays, only a single
isolate, R48-27 demonstrated cellulase, xylanase, chitinase and esterase
activities. In conclusion, the beneficial Lactobacillius spp. strains have the
ability to reduce mycotoxigenic fungi contamination and increase fibrinolytic
activity to improve quality of the S. cereale silage.
PMID- 28402036
TI - Switch in Catalyst State: Single Bifunctional Bi-state Catalyst for Two Different
Reactions.
AB - Disclosed here is a molecular switch which responds to acid-base stimuli and
serves as a bi-state catalyst for two different reactions. The two states of the
switch serve as a highly active and poorly active catalyst for two catalytic
reactions (namely a hydrogenation and a dehydrogenative coupling) but in a
complementary manner. The system was used in an assisted tandem catalysis set-up
involving dehydrogenative coupling of an amine and then hydrogenation of the
resulting imine product by switching between the respective states of the
catalyst.
PMID- 28402038
TI - Delays in postremission chemotherapy for Philadelphia chromosome negative acute
lymphoblastic leukemia are associated with inferior outcomes in patients who
undergo allogeneic transplant: An analysis from ECOG 2993/MRC UK ALLXII.
PMID- 28402039
TI - 2017 Clinical trials update: Innovations in hemophilia therapy.
PMID- 28402037
TI - Atrial electrophysiological and molecular remodelling induced by obstructive
sleep apnoea.
AB - Obstructive sleep apnoea (OSA) affects 9-24% of the adult population. OSA is
associated with atrial disease, including atrial enlargement, fibrosis and
arrhythmias. Despite the link between OSA and cardiac disease, the molecular
changes in the heart which occur with OSA remain elusive. To study OSA-induced
cardiac changes, we utilized a recently developed rat model which closely
recapitulates the characteristics of OSA. Male Sprague Dawley rats, aged 50-70
days, received surgically implanted tracheal balloons which were inflated to
cause transient airway obstructions. Rats were given 60 apnoeas per hour of
either 13 sec. (moderate apnoea) or 23 sec. (severe apnoea), 8 hrs per day for 2
weeks. Controls received implants, but no inflations were made. Pulse oximetry
measurements were taken at regular intervals, and post-apnoea ECGs were recorded.
Rats had longer P wave durations and increased T wave amplitudes following
chronic OSA. Proteomic analysis of the atrial tissue homogenates revealed that
three of the nine enzymes in glycolysis, and two proteins related to oxidative
phosphorylation, were down regulated in the severe apnoea group. Several
sarcomeric and pro-hypertrophic proteins were also up regulated with OSA. Chronic
OSA causes proteins changes in the atria which suggest impairment of energy
metabolism and enhancement of hypertrophy.
PMID- 28402040
TI - Decision-making and future planning for children with life-limiting conditions: a
qualitative systematic review and thematic synthesis.
AB - BACKGROUND: In the last decade, the number of children with life-limiting and
life-threatening conditions in England has almost doubled, and it is estimated
that worldwide, there are 1.2 million children with palliative care needs.
Families and professionals caring for children with life-limiting conditions are
likely to face a number of difficult treatment decisions and develop plans for
future care over the course of the child's life, but little is known about the
process by which these decisions and plans are made. METHODS: The purpose of this
review is to synthesize findings from qualitative research that has investigated
decision-making and future planning for children with life-limiting conditions. A
systematic search of six online databases was conducted and identified 887 papers
for review; five papers were selected for inclusion, using predefined criteria.
Reference list searching and contacting authors identified a further four papers
for inclusion. RESULTS: Results sections of the papers were coded and synthesized
into themes. Nineteen descriptive themes were identified, and these were further
synthesized into four analytical themes. Analytical themes were 'decision
factors', 'family factors', 'relational factors' and 'system factors'.
CONCLUSIONS: Review findings indicate that decision-making and future planning is
difficult and needs to be individualized for each family. However, deficits in
understanding the dynamic, relational and contextual aspects of decision-making
remain and require further research.
PMID- 28402041
TI - Inactivation of ferric uptake regulator (Fur) attenuates Helicobacter pylori J99
motility by disturbing the flagellar motor switch and autoinducer-2 production.
AB - BACKGROUND: Flagellar motility of Helicobacter pylori has been shown to be
important for the bacteria to establish initial colonization. The ferric uptake
regulator (Fur) is a global regulator that has been identified in H. pylori which
is involved in the processes of iron uptake and establishing colonization.
However, the role of Fur in H. pylori motility is still unclear. MATERIALS AND
METHODS: Motility of the wild-type, fur mutant, and fur revertant J99 were
determined by a soft-agar motility assay and direct video observation. The
bacterial shape and flagellar structure were evaluated by transmission electron
microscopy. Single bacterial motility and flagellar switching were observed by
phase-contrast microscopy. Autoinducer-2 (AI-2) production in bacterial culture
supernatant was analyzed by a bioluminescence assay. RESULTS: The fur mutant
showed impaired motility in the soft-agar assay compared with the wild-type J99
and fur revertant. The numbers and lengths of flagellar filaments on the fur
mutant cells were similar to those of the wild-type and revertant cells.
Phenotypic characterization showed similar swimming speed but reduction in
switching rate in the fur mutant. The AI-2 production of the fur mutant was
dramatically reduced compared with wild-type J99 in log-phase culture medium.
CONCLUSIONS: These results indicate that Fur positively modulates H. pylori J99
motility through interfering with bacterial flagellar switching.
PMID- 28402042
TI - MM1-type sporadic Creutzfeldt-Jakob disease with 1-month total disease duration
and early pathologic indicators.
AB - A 62-year-old man presented with abnormal behavior and cognitive impairment.
Diffusion-weighted images (DWI) obtained on MRI showed extensive hyperintense
regions in the cerebral cortex and striatum. Myoclonus was recognized, and the
patient died 1 month after the onset; his condition did not reach the akinetic
mutism state. The brain weighed 1300 g and showed no apparent atrophy. Extensive
spongiform changes were observed in the cerebral neocortex, striatum, thalamus
and cerebellar cortex, but gliosis was mild or absent. Neuropil rarefaction and
neuron loss were not apparent. Mild proliferation of anti- GFAP-positive
astrocytes was observed in the cerebral cortex, but unaffected regions were
noted. Regions without spongiform changes and GFAP-positive astrocytes included
the hippocampal formation and subiculum. PrP immunostaining showed extensive
diffuse synaptic-type PrP deposition in the gray matter, including the
hippocampal region, but it was also mild. PrP gene analysis revealed no mutation
with methionine homozygosity at polymorphic codon 129. Western blot analysis of
proteinase K-resistant PrP indicated type 1 PrPSc . The clinicopathological
findings of the present case confirm several hypotheses: (i) the earliest
pathologic evidence observed by HE staining in CJD are spongiform changes; (ii)
DWI hyperintense regions indicate these spongiform changes; and (iii) regions
without spongiform changes, gliosis and proliferation of GFAP-positive
astrocytes, but with PrP deposition, exist in the early disease stage.
PMID- 28402043
TI - Near-Infrared Circularly Polarized Light Triggered Enantioselective
Photopolymerization by Using Upconversion Nanophosphors.
AB - Circularly polarized light (CPL) is considered to be a true chiral entity and has
been suggested as an explanation for the introduction of initial chiral biases
into key biomolecular building blocks. CPL used recently asymmetric photochemical
reactions is of wavelengths mainly in the UV and visible regions, whereas natural
CPL observed in star-forming regions of the Orion constellation falls in the IR
region. Whether CPL in the IR or near-IR region could be utilized to trigger
asymmetric photochemical reactions remains to be determined. Herein, it is
demonstrated that enantioselective photopolymerization can be realized by using
lambda=980 nm CPL as the only chiral source. By incorporating NaYF4 nanophosphors
as the antenna species, the enantioselective photopolymerization of achiral
benzaldehyde-substituted diacetylene monomer can be realized based on an
upconversion mechanism upon exposure to lambda=980 nm CPL. The screw direction of
the helical PDA chains can be completely controlled by the handedness of incident
lambda=980 nm CPL.
PMID- 28402044
TI - Reported normal values and weighted means for commonly used echocardiography
pulsed Doppler and tissue Doppler measurements.
AB - Pulsed Doppler (PW) and tissue Doppler imaging (TDI) measurements are part of
every echocardiography examination for evaluation of left ventricular (LV)
diastolic function and filling pressure. The purpose of this study was to
summarize published data on normal values for PW and TDI measurements. A PubMed
search was performed on the 10th of October 2016 to identify relevant articles.
Studies were considered relevant if they included more than 200 healthy
individuals. A total of 13 studies were identified. Of these, 13 studies with
7777 subjects reported PW measurement over the mitral valve, six studies with
4082 subjects reported PW measurement in the pulmonary vein and 10 studies with
5988 subjects reported TDI. We also report weighted mean values for 14 different
variables. As expected, measurements varied with age. There were no major
differences between men and women. In contrast, there was a large difference in
reported values between studies, in corresponding age groups. This review
therefore raises caution about relying on normal values from just one study.
PMID- 28402045
TI - Brachial blood flow under relative levels of blood flow restriction is decreased
in a nonlinear fashion.
AB - INTRODUCTION: Blood flow restriction (BFR), the application of external pressure
to occlude venous return and restrict arterial inflow, has been shown to increase
muscular size and strength when combined with low-load resistance exercise. BFR
in the research setting uses a wide range of pressures, applying a pressure based
upon an individual's systolic pressure or a percentage of occlusion pressure; not
a directly determined reduction in blood flow. The relationship between relative
pressure and blood flow has not been established. PURPOSE: To measure blood flow
in the arm under relative levels of BFR. METHODS: Forty-five people (18-40 years
old) participated. Arterial occlusion pressure in the right arm was measured
using a 5-cm pneumatic cuff. Blood flow in the brachial artery was measured at
rest and at pressures between 10% and 90% of occlusion using ultrasound. RESULTS:
Blood flow decreased in a nonlinear, stepped fashion. Blood flow decreased at 10%
of occlusion and remained constant until decreasing again at 40%, where it
remained until 90% of occlusion. CONCLUSION: The decrease in brachial blood flow
is not proportional to the applied relative pressure. The prescription of blood
flow restriction should take into account the stimulus provided at each relative
level of blood flow.
PMID- 28402046
TI - Social cognition and the course of social functioning in first-episode psychosis.
AB - BACKGROUND: Social functioning deficits greatly affect individuals with psychotic
disorders resulting in decreased ability to maintain relationships, jobs and
pursuit of educational goals. Deficits in social cognition have been hypothesized
to be an important contributor to these deficits in social functioning. In
particular, 5 domains of social cognition have been suggested to be relevant in
the study of psychotic disorders: (1) attributional style, (2) emotion
recognition, (3) social knowledge, (4) social perception and (5) theory of mind.
Yet, to date, no study has simultaneously investigated the association between
these 5 domains of social cognition and social functioning. METHODS: We
investigated the cross-section and longitudinal association between social
cognition and social functioning among 71 individuals with first-episode
psychosis. RESULTS: We found modest cross-sectional associations between social
cognition and social functioning that were often in the unexpected direction (ie,
greater social cognition associated with worse social functioning). Social
cognition at baseline was not associated with the longitudinal course of social
functioning. CONCLUSIONS: These unexpected findings fail to align with previous
research that has documented a more robust relationship between these 2
constructs, and raise critical questions with regard to the nature of the
association between social cognition and social functioning among individuals
with first-episode psychosis.
PMID- 28402048
TI - Sensitivity of Helicobacter pylori detection by Giemsa staining is poor in
comparison with immunohistochemistry and fluorescent in situ hybridization and
strongly depends on inflammatory activity.
AB - BACKGROUND: Conventional stainings (including H&E and special stains like Giemsa)
are the most widely applied histopathologic detection methods of Helicobacter
pylori (HP). MATERIALS AND METHODS: We aimed to compare the diagnostic
performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in
situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and
relate results to histologic alterations in order to find such histopathologic
subgroups in which these methods underperform. All cases were categorized
regarding presence or absence of chronic gastritis, inflammatory activity, and
mucosal structural alterations. RESULTS: Giemsa revealed 687 cases (23.7%), IHC
795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed
significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH
(98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the
nonactive cases. We found that sensitivity of Giemsa strongly depends on HP
density and, accordingly, on the presence of activity. Structural alterations
(intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity
of the three stainings. Both IHC and FISH proved to be equally reliable HP
detecting techniques whose diagnostic performance is minimally influenced by
mucosal inflammatory and structural alterations contrary to conventional
stainings. CONCLUSIONS: We highly recommend immunohistochemistry for clinically
susceptible, nonactive chronic gastritis cases, if the conventional stain-based
HP detection is negative. Moreover, we recommend to use IHC more widely as basic
HP stain. Helicobacter pylori FISH technique is primarily recommended to
determine bacterial clarithromycin resistance. Furthermore, it is another
accurate diagnostic tool for HP.
PMID- 28402049
TI - Efficacy of rhythmic exercise and walking exercise in older adults' exercise
participation rates and physical function outcomes.
AB - AIM: The purpose of the present study was to evaluate the efficacy of two
different exercise types, rhythmic exercise designed from local music and dance
(RE) and walking exercise (WE), in terms of exercise participation and physical
function changes in older adults over a period of 12 weeks. METHODS: Exercise
participation was assessed through the attendance rate and retention rate, and
physical function was evaluated through the Short Physical Performance Battery,
static balance test and gait test. RESULTS: The RE group showed significantly
higher attendance and retention rates; greater improvement in Short Physical
Performance Battery scores; and greater improvement in static balance, as
compared with the WE. No differences were found between the RE and WE groups in
gait parameters. CONCLUSIONS: The results suggest that RE was more effective than
WE in retaining exercise participation and improving physical function in older
adults. Geriatr Gerontol Int 2017; 17: 2311-2318.
PMID- 28402047
TI - Survival of Helicobacter pylori in gastric acidic territory.
AB - BACKGROUND: Helicobacter pylori is well adapted to colonize the epithelial
surface of the human gastric mucosa and can cause persistent infections. In order
to infect the gastric mucosa, it has to survive in the gastric acidic pH. This
organism has well developed mechanisms to neutralize the effects of acidic pH.
OBJECTIVE: This review article was designed to summarize the various functional
and molecular aspects by which the bacterium can combat and survive the gastric
acidic pH in order to establish the persistent infections. METHODS: We used the
keywords (acid acclimation, gastric acidic environment, H. pylori and survival)
in combination or alone for pubmed search of recent scientific literatures. One
hundred and forty one papers published between 1989 and 2016 were sorted out. The
articles published with only abstracts, other than in English language, case
reports and reviews were excluded. RESULTS: Many literatures describing the role
of several factors in acid survival were found. Recently, the role of several
other factors has been claimed to participate in acid survival. CONCLUSION: In
conclusion, this organism has well characterized mechanisms for acid survival.
PMID- 28402050
TI - Effects of dietary supplementation with tribasic zinc sulfate or zinc sulfate on
growth performance, zinc content and expression of zinc transporters in young
pigs.
AB - An experiment was conducted to compare the effects of zinc sulfate (ZS) and
tribasic zinc sulfate (TBZ) as sources of supplemental zinc on growth
performance, serum zinc (Zn) content and messenger RNA (mRNA) expression of Zn
transporters (ZnT1/ZnT2/ZnT5/ZIP4/DMT1) of young growing pigs. A total of 96
Duroc * Landrace * Yorkshire pigs were randomly allotted to two treatments and
were fed a basal diet supplemented with 100 mg/kg Zn from either ZS or TBZ for 28
days. Feed : gain ratio in pigs fed TBZ were lower (P < 0.05) than pigs fed ZS,
and average daily weight gain tended to increase (0.05 <= P <= 0.10) in pigs fed
TBZ. Compared with pigs fed ZS, pigs fed TBZ had a higher CuZn-superoxide
dismutase and Zn content in serum (P < 0.05) while they had a lower Zn content in
feces (P < 0.05). In addition, ZIP4 mRNA expression of zinc transporter in either
duodenum or jejunum of pigs fed TBZ were higher (P < 0.05) than pigs fed ZS.
These results indicate that TBZ is more effective in serum Zn accumulation and
intestinal Zn absorption, and might be a potential substitute for ZS in young
growing pigs.
PMID- 28402051
TI - Silage fermentation and ruminal degradation of stylo prepared with lactic acid
bacteria and cellulase.
AB - In order to improve the silage fermentation of stylo (Stylosanthes guianensis) in
tropical areas, stylo silages were prepared with commercial additives
Lactobacillus plantarum Chikuso-1 (CH1), L. rhamnasus Snow Lact L (SN),
Acremonium cellulase (CE) and their combination as SN+CE or CH1 + CE, and the
fermentation quality, chemical composition and ruminal degradation of these
silages were studied. Stylo silages treated with lactic acid bacteria (LAB) or
cellulase, the pH value and NH3 -N / total-N were significantly (P < 0.05)
decreased while the ruminal degradability of dry matter (DM), crude protein (CP),
neutral detergent fiber (aNDFom) and acid detergent fiber (ADFom) were
significantly (P < 0.05) increased compared to control. Compared to LAB or
cellulase-treated silages, the DM, CP contents and relative feed value (RFV), and
the ruminal degradability in LAB plus cellulase-treated silages were
significantly (P < 0.05) higher, but the aNDFom content was significantly (P <
0.05) lower. CH1 + CE treatment was more effective in silage fermentation and
ruminal degradation than SN+CE treatment. The results confirmed that LAB or LAB
plus cellulase treatment could improve the fermentation quality, chemical
composition and ruminal degradation of stylo silage. Moreover, the combined
treatment with LAB and cellulase may have beneficial synergistic effects on
ruminal degradation.
PMID- 28402053
TI - Pseudoreplication and the usage of biomarkers in ecotoxicological bioassays.
AB - Pseudoreplication is a widely discussed topic in the scientific community. Its
principal critique concerns the lack of independence in flawed experimental
designs and the use of inferential statistics to test the hypothesis of such
experiments. Thirty years after its appearance, it remains misunderstood by many
researchers, including ecotoxicologists. In the present study, we try to clarify
some of its concepts by filling in what seems to be a gap in the terminology of
manipulative experiments. We propose the term "experimental medium" to refer
strictly to the relevant spatial scale of the experiment to preserve the
specificity of the experimental and observational units and to display
pseudoreplication as a kind of misinterpretation and/or misanalysis of
inferential statistics. A classification of the types of experimental designs in
ecotoxicology is offered, and the problems in using inferential statistics in
suboptimal designs are discussed. We hope to shed some light on such a classic
topic for ecotoxicologists. Environ Toxicol Chem 2017;36:2868-2874. (c) 2017
SETAC.
PMID- 28402052
TI - Vasopressin casts light on the suprachiasmatic nucleus.
AB - KEY POINTS: A subpopulation of retinal ganglion cells expresses the neuropeptide
vasopressin. These retinal ganglion cells project predominately to our biological
clock, the suprachiasmatic nucleus (SCN). Light-induced vasopressin release
enhances the responses of SCN neurons to light. It also enhances expression of
genes involved in photo-entrainment of biological rhythms. ABSTRACT: In all
animals, the transition between night and day engages a host of physiological and
behavioural rhythms. These rhythms depend not on the rods and cones of the
retina, but on retinal ganglion cells (RGCs) that detect the ambient light level
in the environment. These project to the suprachiasmatic nucleus (SCN) of the
hypothalamus to entrain circadian rhythms that are generated within the SCN. The
neuropeptide vasopressin has an important role in this entrainment. Many SCN
neurons express vasopressin, and it has been assumed that the role of vasopressin
in the SCN reflects the activity of these cells. Here we show that vasopressin is
also expressed in many retinal cells that project to the SCN. Light-evoked
vasopressin release contributes to the responses of SCN neurons to light, and
enhances expression of the immediate early gene c-fos in the SCN, which is
involved in photic entrainment of circadian rhythms.
PMID- 28402054
TI - No evidence of contemporary interploidy gene flow between the closely related
European woodland violets Viola reichenbachiana and V. riviniana (sect. Viola,
Violaceae).
AB - Viola reichenbachiana (2n = 4x = 20) and V. riviniana (2n = 8x = 40) are closely
related species widely distributed in Europe, often sharing the same habitat
throughout their overlapping ranges. It has been suggested in numerous studies
that their high intraspecific morphological variability and plasticity might have
been further increased by interspecific hybridisation in contact zones, given the
sympatry of the species and the incomplete sterility of their hybrid. The aims of
this study were to: (i) confirm that V. reichenbachiana and V. riviniana have one
4x genome in common, and (ii) determine the impact of hybridisation and
introgression on genetic variation of these two species in selected European
populations. For our study, we used 31 Viola populations from four European
countries, which were analysed using AFLP and sequencing of a variable plastid
intergenic spacer, trnH-psbA. Our analysis revealed that V. reichenbachiana
exhibited larger haplotype diversity, having three species-specific haplotypes
versus one in V. riviniana. The relationships among haplotypes suggest transfer
of common haplotypes into V. riviniana from both V. reichenbachiana and
hypothetically the other, now extinct, parental species. AFLP analysis showed low
overall genetic diversity of both species, with V. riviniana showing higher among
population diversity. None of the morphologically designated hybrid populations
had additive AFLP polymorphisms that would have indicated recent hybridisation.
Also, kinship coefficients between both species did not indicate gene flow. V.
riviniana showed significant population subdivision and significant isolation by
distance, in contrast to V. reichenbachiana. The results indicate lack of gene
flow between species, high influence of selfing on genetic variability, as well
as probably only localised introgression toward V. riviniana.
PMID- 28402055
TI - Effects of regular water- and land-based exercise on physical function after 5
years: A long-term study on the well-being of older Japanese adults.
AB - AIM: To investigate the effects of 5 years of physical exercise on functional
parameters among older Japanese adults who carried out water- or land-based
exercise. METHODS: We retrospectively investigated data from 5707 medical
examinations and enrolled 77 older adults into the study. Eligible participants
had to be aged >=60 years, and engaged in water-based exercise (n = 38) or a
combination of water- and land-based exercise (n = 39) for at least 80% of their
total exercise time for over 5 years at our fitness center. In statistical
analysis, a two-way repeated-measures analysis of variance was carried out to
examine the effects over time and by exercise type, and the changes in each
parameter over 5 years were also compared between the two groups. RESULTS: We
found significant main effects and an interaction between time and exercise type
for gait speed, with an early decline in the combined exercise group, as well as
significant main effects of time, showing a functional decline in grip strength,
one-leg standing time and step/height ratio in both exercise types at the 5-year
follow up. The 5-year changes in each parameter did not differ between the two
groups despite the frequency of exercise, even though we found a negative
correlation between changes in one-leg standing time and total amount of water
based exercise. CONCLUSION: Contrary to expectations, these results suggest that
regular engagement in water-based exercise, even combined with land-based
exercise, might have poor long-term benefits for maintaining physical performance
in older adults. Geriatr Gerontol Int 2017; 17: 2116-2123.
PMID- 28402056
TI - Prostaglandin synthesis enzymes' gene transcription in bitches with endometritis.
AB - Endometritis is a major cause of infertility in many domestic species. However,
until now the pathogenesis of the endometritis in the bitch is unclear. The aim
of this study was to evaluate the gene transcription pattern of prostaglandin
(PG) synthesis enzymes (cyclooxygenase [COX2], PTGES-1 and PGFS) in the
endometrium of bitches with or without endometritis. Thirty mixed breed bitches
in dioestrus, aged between 1 and 5 years, and weighing between 10 and 30 kg were
used. After ovariohysterectomy (OVX), uterine biopsy samples were collected from
the middle part of both horns. Then, endometrial epithelium was collected using
the cytobrush method and mRNA analysis was performed by real-time RT-PCR. Data
were analysed with Kruskal-Wallis anova using the sas(r) software. Uterine
condition was identified by endometrial biopsies (normal endometria [n = 11; NE],
acute endometritis [n = 10; AE] and chronic endometritis [n = 9; CE]). The COX2,
PTGES-1 and PGFS/AKR1C3 mRNA expression in bitches with and without endometritis
was similar. Except for PGFS/AKR1C3, gene transcription of COX2 and PTGES-1 was
significantly increased in AE compared with CE. In addition, COX2 gene
transcription was significantly increased in AE compared with NE. In contrast, no
differences were found for COX2, PTGES-1 and PGFS/AKR1C3 mRNA expression in the
samples of NE compared with CE.
PMID- 28402059
TI - Molecular markers of putative spermatogonial stem cells in the domestic cat.
AB - Spermatogonial stem cells (SSCs) are an important tool for fertility preservation
and species conservation. The ability to expand SSCs by in vitro culture is a
crucial premise for their use in assisted reproduction. Because SSCs represent a
small proportion of the germ cells in the adult testis, culture success is aided
by pre-enrichment through sorting techniques based on cell surface-specific
markers. Given the importance of the domestic cat as a model for conservation of
endangered wild felids, herein we sought to examine culture conditions as well as
molecular markers for cat SSCs. Using a cell culture medium for mouse SSCs
supplemented with glial cell-derived neurotrophic factor (GDNF), germ cells from
prepuberal cat testes remained viable in culture for up to 43 days.
Immunohistochemistry for promyelocytic leukaemia zinc finger (PLZF) protein on
foetal, prepuberal and adult testis sections revealed a pattern of expression
consistent with the labelling of undifferentiated spermatogonia. Fluorescence
activated cell sorting (FACS) with an antibody against epithelial cell adhesion
molecule (EPCAM) was used to sort live cells. Then, the gene expression profile
of EPCAM-sorted cells was investigated through RT-qPCR. Notably, EPCAM (+) cells
expressed relatively high levels of CKIT (CD117), a surface protein typically
expressed in differentiating germ cells but not SSCs. Conversely, EPCAM (-) cells
expressed relatively high levels of POU domain class 5 transcription factor 1
(POU1F5 or OCT4), clearly a germ line stem cell marker. These results suggest
that cat SSCs would probably be found within the population of EPCAM (-) cells.
Future studies should identify additional surface markers that alone or in
combination can be used to further enrich SSCs from cat germ cells.
PMID- 28402060
TI - Evaluation of different fragment sizes and cryoprotectants for cryopreservation
of feline testicular tissues.
AB - This study aimed to evaluate tissue damage of feline testicles sectioned in two
different sizes (0.3 or 0.5 cm3 ) and submitted to different cryoprotectants
(propanediol or glycerol). Testicles obtained from 12 domestic cats were
sectioned in 0.3 and 0.5 cm3 sized pieces and immediately evaluated by TBARS and
semi-quantitatively by histomorphology. The remaining fragments were placed in
cryotubes with 1 ml Egg yolk Tris Equex STM extender containing 3% glycerol or 3%
propanediol and cryopreserved by fast-freezing technique. Frozen-thawed fragments
were also evaluated by TBARS and histomorphology. Statistical analysis was
performed using one-way ANOVA with Student-Newmann-Keuls post hoc test, with p <
.05. Fresh and cryopreserved tissues generally exhibited a similar morphology
concerning detachment of cells from the basement membrane and observation of
nucleoli, with a great proportion scored as 0 (no alteration). When present,
alterations were slight and the morphology was considered to be good (most
classified in scores 1). Pyknosis was the main anomaly observed as score 2 in
54.6% and 58.4% of 0.3-cm3 fragments cryopreserved in propanediol and glycerol,
respectively (16.7% scored 2 in fresh tissue). In TBARS evaluation, 0.5-cm3
fragments cryopreserved in glycerol produced less free radical compared to the
0.3 cm3 cryopreserved in glycerol or propanediol. Our results showed that
glycerol was more efficient than propanediol to cryopreserve 0.5-cm3 fragments;
this might be attributed to the fact that glycerol molecular weight is larger
than propanediol and so its perfusion in the testicular tissue is slower.
PMID- 28402061
TI - Comparison of the ovarian and uterine reproductive parameters, and the ovarian
mRNA and protein expression of LHR and FSHR between the prepubertal and adult
female cats.
AB - This study aimed to evaluate and compare the ovarian and uterine characteristics
along with the ovarian mRNA and protein expression of LHR and FSHR between the
pre-pubertal and adult female cats. The uterine horns and ovaries were collected
from pre-pubertal and adult female cats at their follicular, luteal and
interoestrous stages of the oestrous cycle (n = 6/group). Endometrial and
myometrial thickness, uterine gland diameter, ovarian weight and type of
follicles were analysed. The mRNA and protein expression of LHR and FSHR was
analysed by IHC and qPCR, respectively. The ovarian weight of pre-pubertal cats
was significantly lower than that of adult cats. No differences were recorded in
the numbers of primordial and primary follicles between the study groups, while
adult luteal cats had significantly lower numbers of antral follicles compared to
pre-pubertal cats. No differences in the ovarian expression of FSHR mRNA, LHR
protein or mRNA were found between the pre-pubertal and adult cats, but
significantly lower FSHR protein expression was found in pre-pubertal cats
compared to adult luteal cats.
PMID- 28402062
TI - Responsiveness of intraovarian dog follicles in vitro to epidermal growth factor
and vascular endothelial growth factor depends on ovarian donor age.
AB - We investigated the influence of epidermal growth factor (EGF) and vascular
endothelial growth factor (VEGF) on in vitro follicle development within ovarian
cortices recovered from pre-pubertal (<=6 months) versus peri-pubertal dogs (>=10
months). Ovarian cortices were cultured for 3 or 7 days in EGF (0 or 10 ng/ml)
and VEGF (0, 0.1 or 1 ng/ml) and subjected to histological and apoptosis
analyses. Fresh cortices from the same dogs served as "non-cultured controls"
(NCC) and were evaluated similarly. The response of ovarian follicles to growth
factors differed between pre-pubertal versus peri-pubertal tissues. For pre
pubertal dogs, percentage of structurally normal follicles in cortices cultured
for 3 days in low VEGF (0.1 ng/ml) and EGF alone was comparable to that of the
NCC. Follicle density declined in all cultured groups even after 3 days. Primary
follicle diameter in all cortices cultured for 7 days, except in low VEGF, was
smaller than that of the NCC, and percentage apoptotic follicles sharply
increased in all treatment groups compared to the NCC. For peri-pubertal donors,
percentages of structurally normal follicles decreased in all culture treatments
at 3 and 7 days of incubation compared to the NCC. However, more normal follicles
were found in cortices cultured in low VEGF and the two VEGF and EGF combinations
than in the absence of growth factors or with EGF alone. Culture reduced the
density of developing follicles, but follicle diameter was similar to that of the
NCC. TUNEL analysis revealed that high-VEGF (1 ng/ml) treatment protected
follicles against apoptosis, with the proportion of apoptotic follicles at Day 7
being comparable to that of the NCC. The findings demonstrate that the response
of ovarian cortices to growth factor supplementation varied between pre-pubertal
versus peri-pubertal donors.
PMID- 28402063
TI - Reproductive performance and pre-weaning mortality: Preliminary analysis of
27,221 purebred female dogs and 204,537 puppies in France.
AB - The objective of this study was to describe efficiency of reproduction of
purebred dogs in field breeding conditions, from mating to weaning in France.
Data were collected between 2010 and 2014 in 5,667 French breeding kennels via a
reproduction management software (Breeding Management System, Royal Canin,
Aimargues, France). Effect of breed size (Mini: adult body weight <10 kg; Medium:
10-25 kg; Maxi: 25-40 kg; Giant: >40 kg), age of dam and male on pregnancy rate,
abortion rate and litter size were evaluated by multivariable models. Data on
45,913 heats (all with mating), from 27,221 bitches from 248 breeds, were
analysed. At mating, mean age (+/-SD) was 3.1 +/- 1.8 years for bitches and 3.3
+/- 2.0 for males. Males originated from the same kennel as the females in 88.5%
of the matings. Based on breeder's evaluation of the pregnancy status, pregnancy
rate (number of pregnant females based on breeders declaration/number of heats)
was 87.8% and abortion rate was 6.8%. Finally, 81.9% of the mated females gave
birth to a litter. On 37,946 litters (204,537 puppies), mean litter size was 5.4
+/- 2.8 puppies (range 1-24), which was influenced by breed size and dam age (p <
.0001). Stillbirth rate was 7.4% and puppy mortality rate (stillbirth + mortality
until 2 months of age) was 13.4%. Prolificacy and puppy mortality rates were
affected by breed size and within a breed size, by breed. Despite probable
approximations (as data originate from breeders declaration), this large-scale
analysis provides reference values on reproductive performance in dogs.
PMID- 28402064
TI - Use of Psychotropic Medications and Visits to Psychiatrists and Psychologists
among Individuals with Nonsyndromic Oral Clefts: A Population-Based Cohort Study.
AB - BACKGROUND: Oral clefts (OCs) are among the most common congenital malformations
and can have a large impact on the life of the affected individual. Research
findings regarding the psychological and psychosocial consequences of OC are
inconclusive. METHODS: Using Danish nationwide registers, we investigated
redeemed prescriptions of psychotropic medication during 1996 to 2012 and visits
to psychiatrists and psychologists during 1996 to 2011 among individuals born
with nonsyndromic OC in Denmark between 1936 and 2009 and a comparison cohort of
individuals without OC. This includes 8244 individuals with OC and 82,665
individuals without OC. RESULTS: The Cox regression analysis revealed 12% (95%
confidence interval [CI], 7 to 16%) increased risk of using any psychotropic
medication for individuals with OC. When examining by cleft type, higher risks
for medication use were observed in individuals with cleft lip and palate (CLP)
or cleft palate (CP) only. The largest increased relative risk was found for use
of antipsychotics and stimulants for individuals with CP followed by use of
antipsychotics for individuals with CLP. We found increased risk of visits to
psychiatrists for individuals with CP and no increased risk for visits to
psychologists for either group. CONCLUSIONS: This study indicates that a small
group of individuals with nonsyndromic OC, in particular those with palatal
involvement, have greater risk of using psychotropic medications. However,
elevated use was also observed among younger individuals with cleft lip (CL)
only. There seems to be only a modest increase in visits to health professionals
for psychological reasons. Undiagnosed syndromes (e.g., 22q11 deletion syndrome),
may, however, contribute to an overestimation of the associations. Birth Defects
Research 109:824-835, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28402066
TI - Redox-Neutral Dual Functionalization of Electron-Deficient Alkenes.
AB - Visible-light photoredox catalysis has been utilized in a new multicomponent
reaction forming beta-functionalized delta-diketones under mild conditions in an
operationally convenient manner. Single-electron reduction of in situ generated
carboxylic acid derivatives forms acyl radicals that react further via 1,2
acylalkylation of olefins in an intermolecular, three-components cascade
reaction, giving valuable synthetic entities from readily available starting
materials. A diverse set of substrates has been used, demonstrating robust
methodology with broad substrate scope.
PMID- 28402067
TI - Altered Reward Reactivity as a Behavioural Endophenotype in Eating Disorders: A
Pilot Investigation in Twins.
AB - Altered reward reactivity is a potential risk endophenotype for eating disorders
(EDs). The aim of this study was to examine reward reactivity in female twins
with EDs and compare it with a twin control group. A sample of 112 twins [n = 51
met lifetime DSM-IV ED criteria (anorexia nervosa n = 26; bulimic disorders n =
24), n = 19 unaffected cotwins and n = 42 control twins] was administered
measures assessing reward reactivity, including the Game of Dice Task, the
Behavioural Inhibition/Activation (BIS/BAS) Scales and the Appetitive Motivation
Scale (AMS). Within pair, correlations for monozygotic and dizygotic twins were
calculated and generalised estimating equations compared probands with non-ED
cotwins and controls. The BAS and the AMS were reduced in EDs and negatively
associated with restrictive symptoms. In addition, monozygotic twins pairs
demonstrated significant within pair similarity for the BAS and AMS. Conversely,
there was less evidence to support the BIS or risky decision-making as measured
by the Game of Dice Task as an endophenotype in EDs. Copyright (c) 2017 John
Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28402065
TI - Identification of a synergistic interaction between endothelial cells and retinal
pigment epithelium.
AB - The retinal pigment epithelium located between the neurosensory retina and the
choroidal vasculature is critical for the function and maintenance of both the
photoreceptors and underlying capillary endothelium. While the trophic role of
retinal pigment epithelium on choroidal endothelial cells is well recognized, the
existence of a reciprocal regulatory function of endothelial cells on retinal
pigment epithelium cells remained to be fully characterized. Using a
physiological long-term co-culture system, we determined the effect of retinal
pigment epithelium-endothelial cell heterotypic interactions on cell survival,
behaviour and matrix deposition. Human retinal pigment epithelium and endothelial
cells were cultured on opposite sides of polyester transwells for up to 4 weeks
in low serum conditions. Cell viability was quantified using a trypan blue assay.
Cellular morphology was evaluated by H&E staining, S.E.M. and
immunohistochemistry. Retinal pigment epithelium phagocytic function was examined
using a fluorescent bead assay. Gene expression analysis was performed on both
retinal pigment epithelium and endothelial cells by quantitative PCR.
Quantification of extracellular matrix deposition was performed on decellularized
transwells stained for collagen IV, fibronectin and fibrillin. Our results showed
that presence of endothelial cells significantly improves retinal pigment
epithelium maturation and function as indicated by the induction of visual cycle
associated genes, accumulation of a Bruch's membrane-like matrix and increase in
retinal pigment epithelium phagocytic activity. Co-culture conditions led to
increased expression of anti-angiogenic growth factors and receptors in both
retinal pigment epithelium and endothelial cells compared to monoculture. Tube
formation assays confirmed that co-culture with retinal pigment epithelium
significantly decreased the angiogenic phenotype of endothelial cells. These
findings provide evidence of critical interdependent interactions between retinal
pigment epithelium and endothelial cell involved in the maintenance of retinal
homeostasis.
PMID- 28402068
TI - Eating-related Psychopathology and Food Addiction in Adolescent Psychiatric
Inpatients.
AB - OBJECTIVE: Our aims were to investigate the relationship between food addiction
and mental disorders including eating disorders (ED), eating-related
psychopathology and body mass index-standard deviation score in a sample of
adolescent psychiatric inpatients. METHODS: Food addiction was assessed with the
Yale Food Addiction Scale (YFAS). Eating-related psychopathology was measured
with the Three-Factor Eating Questionnaire (TFEQ). Psychiatric diagnoses were
assessed according to the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition. The sample consisted of n = 242 adolescent psychiatric
inpatients, of which n = 37 (15.3%) met criteria for an ED. Multiple regression
analysis was used to examine the association between YFAS symptom count, TFEQ
scales and ED controlling for age and gender. RESULTS: Food addiction frequency
was 16.5%, and the mean YFAS symptom count was 2.39 (SD: 1.60). In patients with
food addiction, TFEQ scale scores were significantly higher than patients without
food addiction. Frequency of ED was 42.9% in patients with and 9.9% in patients
without food addiction. The TFEQ subscales disinhibition and hunger as well as
diagnosis of ED were associated with YFAS symptom count. DISCUSSION: Food
addiction in adolescent psychiatric inpatients occurs with rates higher than
those seen in community samples of children, adolescents and adults. Food
addiction might be associated with eating styles related to susceptibility to
hunger and feelings of loss of control. The implications of high-YFAS scores in
restricting-type anorexia nervosa warrant further investigations to explore which
and how the respective items are interpreted in this ED subgroup. Copyright (c)
2017 John Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28402069
TI - Anorexia Nervosa, Theory and Treatment: Where Are We 35 Years on from Hilde
Bruch's Foundation Lecture?
AB - Hilde Bruch's foundation lecture in 1982 is a milestone from which to survey
current theory and treatment for anorexia nervosa. Bruch described problems in
body perception, emotion processing and interpersonal relationships as core
theoretical aspects of the illness and built her theory of psychopathology on
these aspects, as well as on animal studies on attachment. She also noted that
many psychological problems result as consequence of starvation. In the first
part of this paper, we parse Bruch's clinical descriptions into elements of
psychopathology (disturbances in body perception, attachment, emotion expression,
perception and regulation, social comparison, interpersonal, and family and
therapeutic relationships), in order to assemble and update the theoretical
evidence for a model of the illness. In the second part, we describe and extend
her description of three core targets of treatment: family relationships,
patient's inner confusion and nutritional restoration. Copyright (c) 2017 John
Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28402070
TI - Evaluation of the DSM-5 Severity Indicator for Anorexia Nervosa.
AB - OBJECTIVE: This study tested the new DSM-5 severity criterion for anorexia
nervosa (AN) based on proposed body mass index (BMI) cut-points. METHOD:
Participants were a clinical sample of 201 treatment-seeking patients diagnosed
with DSM-5 AN in Portugal. Participants were categorised based on DSM-5 severity
levels and were compared on demographic and clinical variables assessed with the
Eating Disorder Examination-Questionnaire. RESULTS: Based on DSM-5 severity
definitions for AN, 73 (36.3%) participants were categorised as mild (>=17.0
BMI), 40 (19.9%) as moderate (16-16.99 BMI), 30 (14.9%) as severe (15-15.99 BMI)
and 58 (28.9%) as extreme (<15 BMI). The severity groups did not differ
significantly in age or gender. Analyses comparing the severity groups on
measures of eating-disorder psychopathology revealed no significant differences
on the Eating Disorder Examination-Questionnaire global or subscale scores. The
groups also did not differ significantly on the frequency of binge eating or
purging episodes within the past 28 days. CONCLUSIONS: Our findings, in this
clinical sample of patients with AN in Portugal, provide no evidence for the new
DSM-5 severity ratings based on BMI level. Further research on the validity of
the DSM-5 specifiers is needed and should test additional clinical or functional
variables and especially prognostic utility for course and outcome across eating
disorders. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders
Association.
PMID- 28402071
TI - Successful use of propranolol for congenital hepatic hemangioma with Kasabach
Merritt phenomenon.
PMID- 28402072
TI - Congenital Lung Agenesis: Incidence and Outcome in the North of England.
AB - BACKGROUND: Unilateral lung agenesis is an uncommon congenital abnormality, with
a lack of reported accurate incidence estimates. Prognosis is also uncertain,
with older literature reporting poor outcomes. METHODS: The North of England
register of congenital anomalies (Northern Congenital Abnormality Survey) records
cases of congenital anomalies to mothers' resident in the region. We used the
register to identify all patients with congenital lung agenesis born between 2004
and 2013 to calculate an accurate incidence estimate and report clinical outcomes
with contemporary management. RESULTS: Four patients with congenital lung
agenesis were born during the study period, giving an estimated incidence in the
North of England of 1.22 per 100,000 live births (95% confidence interval, 0.33
3.11). Two patients had associated congenital heart disease requiring corrective
surgery, and one had musculoskeletal anomalies. All four patients are alive and
well without a regular oxygen requirement. CONCLUSION: Contrary to previous
reports, the medium term outcomes in our patients have been good, even when lung
agenesis is associated with other congenital anomalies. Long-term prognosis with
modern management remains unknown, and the potential for the development of
pulmonary hypertension remains a concern. Birth Defects Research 109:857-859,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28402074
TI - Prevalence and risk factors of depression in the empty nest elderly from the
Sichuan Longmenshan fault earthquake.
AB - AIM: There have been few recent studies that have systematically investigated the
risk factors for psychological illnesses caused by earthquakes in the empty nest
elderly. The aim of this study was to determine the prevalence and risk factors
for depression in this special group in the hardest hit areas of the 2008 Sichuan
Longmenshan fault Earthquake. METHODS: A cross-sectional study was conducted in
10 severely damaged counties from Oct 2015 to Jan 2016 on 1,783 empty nesters,
all of whom completed the Geriatric Depression Scale and the Social Support
Rating Scale. Socio-demographic information was also collected in a cross
sectional survey. RESULTS: It was found that 83.1 % of empty nesters had
depression overall, with 94.5 % in females, 95.8 % in the single elderly (widowed
or divorced) and 97.7 % in those who had suffered bereavement because of the
earthquake. The logistic regression analysis showed that being female, of single
status, having poor subjective support, poor support availability and suffering
from bereavement were the main risk factors for depression. CONCLUSIONS: Of the
earthquake affected empty nest elderly, depression was highest in females and the
bereaved. Further poor subjective support was found to be strong indicator of
depression in this special group. To minimize depression in the vulnerable
elderly, measures should be taken to assist empty nesters in the earthquake
stricken areas make full use of social support. Geriatr Gerontol Int 2017; 17:
2143-2149.
PMID- 28402073
TI - Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and
Treatment.
AB - Infantile hemangiomas (IHs) are the most common vascular tumors in infants,
appearing in early infancy and ultimately regressing with time. Clinical
presentation may vary, with a minority of lesions causing impairment of vital
function (e.g., respiratory or visual obstruction), permanent scarring, and/or
disfigurement. The pathogenesis of IH is complex and poorly understood. Risk
factors implicated in their development include preterm birth and placental
anomalies. IH presents a myriad of clinical challenges, including correct
diagnosis and whether or not to pursue treatment. This article is a review of the
current literature regarding pathogenesis, clinical presentation, treatment, and
prognosis of IH. Birth Defects Research 109:809-815, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28402077
TI - Japan Prize: E. Charpentier and J. A. Doudna / Special Award in Synthetic Organic
Chemistry, Japan: K. Sonogashira / CNRS Medals: L. Fensterbank, C. Allain, M.
Raynal, S. Ulrich, S. Cavaliere, C. Matei Ghimbeu, and A. Gautier.
PMID- 28402076
TI - Studies on supplementary desalted mother liquor on digestibility of nutrients,
ruminal fermentation, and energy and nitrogen balance in Thai native cattle.
AB - Four Thai native steers were used to determine the adequate levels of
supplementary desalted mother liquor (DML) for energy and nitrogen balances and
ruminal fermentation. The crude protein and sodium chloride contents of DML were
25.5% and 60.3% on a dry matter (DM) basis, respectively. A 4 * 4 Latin square
design experiment was conducted by adding different amounts of DML to three
experimental diets (T1: 1.1%, T2: 2.2%, T3: 3.4% sodium chloride concentration
with supplementary DML on a DM basis) and comparing their effects with those of a
control diet (C) containing 1.0% commercial salt on a DM basis. The animals were
given the experimental diets and rice straw daily at 1.2% and 0.8% of body
weight, respectively, on a DM basis. No significant differences in the apparent
digestibility of nutrients were observed among treatments. T3 achieved the lowest
nitrogen retention (P < 0.05), followed by C, T2 and T1. The ratios of energy
retention to gross energy were higher in T1 and T3 than T2, and that in C was
lowest (P < 0.05). Supplementary NaCl concentration at 1% and 2% can be replaced
with DML without an adverse effect on the digestibility of nutrients or on the
nitrogen and energy retention.
PMID- 28402078
TI - Total atherosclerotic burden measured by magnetic resonance imaging is related to
five-year decline in cognitive function.
AB - OBJECTIVE: The aim of this study was to explore whether total atherosclerotic
burden is related to future decline in performance on cognitive tests. METHODS:
The total atherosclerotic burden (TAS) was assessed by whole-body magnetic
resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective
Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini-mental state
examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75
and 80 in 190 of those subjects. No subject with a diagnosis of dementia was
included in the sample. RESULTS: MMSE did not change during the 5 years of follow
up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was
significantly related to the individual change in TMT B (P<0.0001) between age 75
and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham
score at age 70. No such relationship was seen for the change in TMT A (P =
0.10). The relationship between TAS and the change in MMSE was of borderline
significance (P = 0.025). CONCLUSION: A relationship was found between the total
atherosclerotic burden and future decline in performance on TMT B, highlighting a
role of global atherosclerosis in the cognitive decline seen during ageing.
PMID- 28402079
TI - Inverse association between size of the lipid-rich necrotic core and
vascularization in human carotid plaques.
AB - PURPOSE: To study the relationship between the size of the lipid-rich necrotic
core measured by MRI (magnetic resonance imaging) and the level of plaque
vascularization measured by contrast-enhanced ultrasound, in human carotid
plaques. Further, to compare the size of lipid-rich necrotic core from MRI to
plaque echogenicity. METHODS: Thirty-one subjects with carotid plaques underwent
standard B-mode ultrasound, contrast-enhanced ultrasound and MRI. The lipid-rich
necrotic core was quantified using MRI. Contrast-enhanced ultrasound was used to
measure carotid plaque vascularization. Standard B-mode ultrasound was used to
measure plaque echogenicity as greyscale median. RESULTS: The amount of lipid
rich necrotic core correlated inversely with the degree of plaque vascularization
(r = -0.40, P = 0.03). There were no correlations between the degree of plaque
vascularization and the amount of fibrous tissue or calcifications. There were no
correlations between greyscale median and the lipid-rich necrotic core, fibrous
tissue or calcifications. CONCLUSIONS: We show that more dense plaque
vascularization is associated with a lower plaque content of lipid-rich necrotic
core. A large lipid-rich necrotic core and high plaque vascularization are both
proposed as predictors of vulnerability, and our finding is therefore odds with
some earlier observations. Our finding can be explained by the fact that the
necrotic core of the plaque contains no viable tissue and therefore less of the
plaque can be vascularized if the lipid-rich necrotic core is large. Our study
suggests that the true relation between plaque vascularization and other indices
of vulnerability is more complex than initially thought.
PMID- 28402081
TI - Doctors and Uxoricide: What Can We Learn From Tragedy?
PMID- 28402080
TI - Application of ischemic postconditioning's algorithms in tissues protection:
response to methodological gaps in preclinical and clinical studies.
AB - Ischaemic postconditioning (IPostC) was introduced for the first time by Zhao et
al. as a feasible method for reduction of myocardial ischaemia-reperfusion (IR)
injury. The cardioprotection by this protocol has been extensively evaluated in
various species. Then, further research revealed that IPostC is a safe and
convenient approach in limiting IR injury of non-myocardial tissues such as lung,
liver, kidney, intestine, skeletal muscle, brain and spinal cord. IPostC has been
conducted with different algorithms, resulting in diverse effects. The possible
important factors leading to these differences are the difference in activation
levels of signalling pathways and protective mediators by any algorithm, presence
or absence of IPostC effectors in each tissue, or intrinsic characteristics of
the tissues as well as the methodological biases. Also, the conflicting results
have been shown with the application of the same algorithm of IPostC in certain
tissues or animal species. The effectiveness of IPostC may depend upon various
parameters including the species and the tissues characteristics. For example,
different heart rates and metabolic rates of the species and unequal amounts of
perfusion and blood flow of the tissues should be considered as the important
determinants of IPostC effectiveness and should be thought about in designing
IPostC algorithms for future studies. Due to these discrepancies, there is still
no optimal single IPostC algorithm applicable to any tissue or any species. This
issue is the main topic of the present article.
PMID- 28402083
TI - Long-chain ionic liquid based mixed hemimicelles and magnetic dispersed solid
phase extraction for the extraction of fluorescent whitening agents in paper
materials.
AB - A novel mixed hemimicelles and magnetic dispersive solid-phase extraction method
based on long-chain ionic liquids for the extraction of five fluorescent
whitening agents was established. The factors influenced on extraction efficiency
were investigated. Under the optimal conditions, namely, the pH of sample
solution at 8.0, the concentration of long chain ionic liquid at 0.5 mmol/L, the
amount of Fe3 O4 nanoparticle at 12 mg, extraction time at 10 min, pH 6.0 of
methanol as eluent, and the desorption time at 1 min, satisfactory results were
obtained. Wide linear ranges (0.02-10 ng/mL) and good linearity were attained
(0.9997-0.9999). The intraday and interday RSDs were 2.1-8.3%. Limits of
detection were 0.004-0.01 ng/mL, which were decreased by almost an order of
magnitude compared to direct detection without extraction. The present method was
applied to extract the fluorescent whitening agents in two kinds of paper
samples, obtaining satisfactory results. All showed results illustrated that the
detection sensitivity was improved and the proposed method was a good choice for
the enriching and monitoring of trace fluorescent whitening agents.
PMID- 28402084
TI - Foreign bodies in the external auditory canal: Influence of age on incidence and
outcomes in a Japanese population.
AB - AIM: Otolaryngologists occasionally observe foreign bodies (FB) in the external
auditory canal (EAC), although relatively few studies have focused on the role of
age in this condition. METHODS: We retrospectively compared the incidences,
outcomes and complications of FB in the EAC in different age groups. RESULTS: The
patients at our center included 24 children (19%), 46 adults (37%) and 56 older
adults (44%). Compared with adults, older adults were significantly more likely
to have FB (peak age 75-79 years), be women (18/46 vs 34/56, P = 0.0461) and be
unaware of their FB (18/46 vs 34/56, P = 0.0461). We observed that all EAC FB
were more common during the summer, and biotic FB were not observed during the
winter. Complications were more common in cases of biotic FB, compared with
abiotic FB (5/27 vs 6/99, P = 0.0421). CONCLUSION: Our findings show that older
adults are particularly susceptible to FB, are frequently unaware of their FB and
can develop complications. These characteristics should be considered before
treating FB in the EAC. Geriatr Gerontol Int 2017; 17: 2131-2135.
PMID- 28402085
TI - Decision aids for people facing health treatment or screening decisions.
AB - BACKGROUND: Decision aids are interventions that support patients by making their
decisions explicit, providing information about options and associated
benefits/harms, and helping clarify congruence between decisions and personal
values. OBJECTIVES: To assess the effects of decision aids in people facing
treatment or screening decisions. SEARCH METHODS: Updated search (2012 to April
2015) in CENTRAL; MEDLINE; Embase; PsycINFO; and grey literature; includes CINAHL
to September 2008. SELECTION CRITERIA: We included published randomized
controlled trials comparing decision aids to usual care and/or alternative
interventions. For this update, we excluded studies comparing detailed versus
simple decision aids. DATA COLLECTION AND ANALYSIS: Two reviewers independently
screened citations for inclusion, extracted data, and assessed risk of bias.
Primary outcomes, based on the International Patient Decision Aid Standards
(IPDAS), were attributes related to the choice made and the decision-making
process.Secondary outcomes were behavioural, health, and health system effects.We
pooled results using mean differences (MDs) and risk ratios (RRs), applying a
random-effects model. We conducted a subgroup analysis of studies that used the
patient decision aid to prepare for the consultation and of those that used it in
the consultation. We used GRADE to assess the strength of the evidence. MAIN
RESULTS: We included 105 studies involving 31,043 participants. This update added
18 studies and removed 28 previously included studies comparing detailed versus
simple decision aids. During the 'Risk of bias' assessment, we rated two items
(selective reporting and blinding of participants/personnel) as mostly unclear
due to inadequate reporting. Twelve of 105 studies were at high risk of bias.With
regard to the attributes of the choice made, decision aids increased
participants' knowledge (MD 13.27/100; 95% confidence interval (CI) 11.32 to
15.23; 52 studies; N = 13,316; high-quality evidence), accuracy of risk
perceptions (RR 2.10; 95% CI 1.66 to 2.66; 17 studies; N = 5096; moderate-quality
evidence), and congruency between informed values and care choices (RR 2.06; 95%
CI 1.46 to 2.91; 10 studies; N = 4626; low-quality evidence) compared to usual
care.Regarding attributes related to the decision-making process and compared to
usual care, decision aids decreased decisional conflict related to feeling
uninformed (MD -9.28/100; 95% CI -12.20 to -6.36; 27 studies; N = 5707; high
quality evidence), indecision about personal values (MD -8.81/100; 95% CI -11.99
to -5.63; 23 studies; N = 5068; high-quality evidence), and the proportion of
people who were passive in decision making (RR 0.68; 95% CI 0.55 to 0.83; 16
studies; N = 3180; moderate-quality evidence).Decision aids reduced the
proportion of undecided participants and appeared to have a positive effect on
patient-clinician communication. Moreover, those exposed to a decision aid were
either equally or more satisfied with their decision, the decision-making
process, and/or the preparation for decision making compared to usual
care.Decision aids also reduced the number of people choosing major elective
invasive surgery in favour of more conservative options (RR 0.86; 95% CI 0.75 to
1.00; 18 studies; N = 3844), but this reduction reached statistical significance
only after removing the study on prophylactic mastectomy for breast cancer gene
carriers (RR 0.84; 95% CI 0.73 to 0.97; 17 studies; N = 3108). Compared to usual
care, decision aids reduced the number of people choosing prostate-specific
antigen screening (RR 0.88; 95% CI 0.80 to 0.98; 10 studies; N = 3996) and
increased those choosing to start new medications for diabetes (RR 1.65; 95% CI
1.06 to 2.56; 4 studies; N = 447). For other testing and screening choices,
mostly there were no differences between decision aids and usual care.The median
effect of decision aids on length of consultation was 2.6 minutes longer (24
versus 21; 7.5% increase). The costs of the decision aid group were lower in two
studies and similar to usual care in four studies. People receiving decision aids
do not appear to differ from those receiving usual care in terms of anxiety,
general health outcomes, and condition-specific health outcomes. Studies did not
report adverse events associated with the use of decision aids.In subgroup
analysis, we compared results for decision aids used in preparation for the
consultation versus during the consultation, finding similar improvements in
pooled analysis for knowledge and accurate risk perception. For other outcomes,
we could not conduct formal subgroup analyses because there were too few studies
in each subgroup. AUTHORS' CONCLUSIONS: Compared to usual care across a wide
variety of decision contexts, people exposed to decision aids feel more
knowledgeable, better informed, and clearer about their values, and they probably
have a more active role in decision making and more accurate risk perceptions.
There is growing evidence that decision aids may improve values-congruent
choices. There are no adverse effects on health outcomes or satisfaction. New for
this updated is evidence indicating improved knowledge and accurate risk
perceptions when decision aids are used either within or in preparation for the
consultation. Further research is needed on the effects on adherence with the
chosen option, cost-effectiveness, and use with lower literacy populations.
PMID- 28402086
TI - The effect of increased microporosity on bone formation within silicate
substituted scaffolds in an ovine posterolateral spinal fusion model.
AB - This study compared the bone forming capacity of the same formulation of silicate
substituted bone graft substitute materials with different microporosity in an
instrumented posterolateral spinal fusion ovine model. Materials with a strut
porosity of (i) 22.5% (SiCaP) or (ii) 36.0% (SiCaP(+)) were packed along either
side of the spine. Bone apposition rates, % new bone formation, % bone-implant
contact, and % graft resorption were quantified at 8, 12, and 24 weeks post
surgery. Computed Tomography (CT) was used to grade the formation of fusion
bridges between vertebrae. Results showed no significant difference in bone
apposition rates, % new bone formation, and % bone-implant contact when the two
materials were compared. However, at 8 weeks, a significantly higher CT score was
obtained in the SiCaP(+) group (0.83 +/- 0.17) when compared with the SiCaP group
(0.17 +/- 0.17; p = 0.027). Significantly less scaffold remained in the SiCaP(+)
group at 12 weeks (p = 0.018). Both SiCaP and SiCaP(+) formulations augmented
bone formation. Increasing the strut porosity did not significantly increase bone
formation however, at 8 weeks it promoted the formation of more highly
mineralized bone resulting in a significantly higher CT score, suggesting the
bone tissue formed was more mature. (c) 2016 Wiley Periodicals, Inc. J Biomed
Mater Res Part B: Appl Biomater, 105B: 805-814, 2017.
PMID- 28402087
TI - Kluyvera ascorbata infection in a neonate.
PMID- 28402088
TI - The Mozart study: a relation between dynamic hyperinflation and physical activity
in patients with chronic obstructive pulmonary disease?
AB - BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD)
experience dyspnoea during exercise, resulting in a reduction of physical
activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea
in COPD. OBJECTIVE: The objective of the current study was to investigate the
relationship between DH, in terms of the amount of DH and the development and
recovery rate of DH in patients with COPD, and PA. METHODS: Thirty-five patients
with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD
III, median age 65). PA was assessed using an accelerometer. Subjects underwent
metronome-paced tachypnoea (MPT) to induce DH. To quantify the amount of DH
during MPT, a decrease in inspiratory capacity (IC) or a change in IC as
percentage of total lung capacity was used. RESULTS: No significant correlations
were found between the parameters describing DH and PA. Secondary correlation
analyses showed a negative correlation between static hyperinflation (SH) and PA
(r = -0.39; P = 0.02). The pattern of breathing during MPT and the test itself
showed high interpatient variability. CONCLUSIONS: The absence of a significant
correlation between DH and PA is contrary to previous studies. SH did show a
correlation with PA. The variety in results and the technical difficulties in
execution of the measurements ask for a new, more reliable, method to detect DH
and investigate its relation with PA in patients with COPD.
PMID- 28402090
TI - Terminal illness: can we prevent suffering?
PMID- 28402089
TI - Perioperative management of obstructive sleep apnea: a systematic review.
AB - INTRODUCTION: Obstructive sleep apnea (OSA) is the leading sleep disordered
breathing condition, with a prevalence rate of moderate to severe OSA of
approximately 10-17% in the general population. EVIDENCE ACQUISITION: We
performed an Ovid-Medline search of all articles published up to August 2016. We
included all articles providing updated evidence on epidemiology,
pathophysiologic mechanisms and perioperative interventions. EVIDENCE SYNTHESIS:
OSA is associated with a number of comorbidities and increased perioperative
risks. Although in-laboratory polysomnography represents the gold-standard for
diagnosis of OSA, it is costly and time-consuming. Anesthesiologists may screen
patients for OSA through one of the available questionnaires, of which the
snoring, tiredness, observed apnea, high blood pressure (STOP)-Body Mass Index,
age, neck circumference and gender (Bang), STOP-bang questionnaire is the most
externally validated. Although its sensitivity for the identification of mild OSA
patients is 83.6%, its specificity is only 56.4%. OSA patients are associated
with a higher risk of both difficult ventilation and intubation. However,
practice guidelines refer to available guidelines for difficult airway
management. Perioperative continuous positive airway pressure use may be of
benefit since it has been reported to be associated with a reduction of both
respiratory and cardiovascular complications and symptom relief. When feasible,
regional anesthesia techniques and a multimodal analgesia approach should be
adopted to reduce intraoperative and postoperative exposure to opioids.
CONCLUSIONS: Preoperative screening of OSA patients is of relevance given the
increased perioperative morbidity of these patients. Further studies are needed
to provide conclusive data on which perioperative interventions are most
effective at reducing this risk.
PMID- 28402091
TI - Thoracic trauma and acute respiratory distress syndrome in polytraumatized
patients: a retrospective analysis.
AB - BACKGROUND: Although thoracic trauma has often been associated with the
development of acute respiratory distress syndrome (ARDS) in general, its impact
on ARDS in combination with severe concomitant injuries has still to be
elucidated. Therefore, the objective of this study was to determine the frequency
of thoracic trauma and ARDS in polytraumatized patients, and to evaluate the
impact of thoracic trauma on the occurrence and the onset of ARDS. METHODS:
Included in this retrospective cohort study were all polytraumatized patients
over 18 years of age, with an injury severity score (ISS) of at least 16, who
were admitted to our level I trauma center over a three-year time period.
RESULTS: Two hundred and eighty-eight patients met the inclusion criteria. 54.9%
suffered from thoracic trauma, 51.7% developed ARDS, 21.5% pneumonia and 0.7%
pulmonary embolism. Independent of the ISS, the presence of thoracic trauma
increased the odds of ARDS occurrence (OR=2.242; 95% CI: 1.381-3.640; P<0.001)
and resulted in a significantly earlier onset of ARDS (median, day 2 vs. day 3;
P<0.01). Of those patients suffering from ARDS, ventilation time and length of
stay at the ICU were longer if a concomitant thoracic injury was present
(P<0.001). In general, ARDS was diagnosed prior to pneumonia and was therefore
identified as its risk factor (OR=11.033; 95% CI: 4.812-25.299; P<0.001).
Finally, an overall mortality rate of 21.2% was observed, which was neither
affected by thoracic trauma nor ARDS. CONCLUSIONS: Thoracic trauma was identified
as major risk factor for ARDS occurrence and earlier onset in polytrauma victims.
PMID- 28402092
TI - Ultrasound-determined landmarks decrease pressure pain at epidural insertion site
in immediate post-partum period.
AB - BACKGROUND: Women have blamed epidurals for their post-partum back pain for
decades. Survey-based studies have shown similar incidence of chronic back pain
between women who delivered with epidurals compared to those who did not.
However, epidural insertion site pain has yet to be evaluated by a quantitative
measure: pressure pain threshold (PPT). Algometer measured PPT has been shown to
be accurate and reproducible in acute, chronic, and postoperative pain studies.
This study determines the effect of ultrasound-based landmarks on the PPT at the
epidural insertion site in the post-partum period. METHODS: Participants were
randomized into either the ultrasound or sham groups. In addition, a non
randomized control group (no epidural) participated. Ultrasound of the lumbar
region was used to mark mid intervertebral levels in the US group but not in the
sham group. Epidural were placed using the marks in the US group or palpated bony
landmarks in the sham group. PPT at each intervertebral space measured before and
after the use of epidural. RESULTS: Epidural placement did significantly
decreased PPT in US (68%) and US sham (79%) groups and less in the control group
(21%). US group showed decreased PPT only at insertion site whereas US sham group
also showed decreased PPT at insertion site and adjacent levels. CONCLUSIONS: We
showed that epidural placed with ultrasound-determined landmarks not only
improves the success of epidural placement but also minimizes the number of
intervertebral levels with decreased PPT.
PMID- 28402093
TI - Extracorporeal CO2 removal in critically ill patients: a systematic review.
AB - INTRODUCTION: The use of extracorporeal CO2 removal (ECCO2R) is increasingly
employed in critically ill patients. However, the clinical evidence supporting
its efficacy remains currently poor. EVIDENCE ACQUISITION: A systematic review
using MEDLINE via PubMed was performed to identify eligible studies (until 30th
September 2016). The amount of CO2 reduction, the effect on the duration of
mechanical ventilation and weaning, the impact on patients' outcome and the
occurrence of complications were evaluated. The quality of evidence was evaluated
according to the GRADE (Grading of Recommendations Assessment, Development and
Evaluation) criteria. EVIDENCE SYNTHESIS: Six studies were included (three
evaluating patients with chronic obstructive pulmonary disease [COPD]; three
evaluating patients with acute respiratory distress syndrome [ARDS]), involving
279 adult patients; 142 treated with ECCO2R and 137 controls. No study on
pediatric population met the inclusion criteria for analysis. The overall quality
of evidence of the two randomized trials and four case-control studies varied
from moderate to very low. PaCO2 was generally reduced by 25-33% within a few
hours following ECCO2R initiation. One ARDS study showed a significant decrease
in the duration of mechanical ventilation, although this result was only found by
post-hoc analysis. The three studies on COPD demonstrated that some patients
supported by ECCO2R devices could avoid endotracheal intubation, however the ICU
LOS and survival was not influenced by ECCO2R when compared to controls.
CONCLUSIONS: In COPD patients, a significantly reduced need for endotracheal
intubation was reported. However, the use of ECCO2R has not shown significant
improvement on the outcome of critically ill patients in the reviewed studies.
Therefore appropriately powered, randomized, controlled studies are urgently
needed.
PMID- 28402094
TI - Effect of anesthesia methods on postoperative major adverse cardiac events and
mortality after non-cardiac surgeries: a systematic review and meta-analysis.
AB - INTRODUCTION: Postoperative major adverse cardiac events (MACEs) are the main
cause of postoperative mortality, and controversies exist regarding the effects
of anesthesia methods on postoperative MACEs and mortality in high-risk cardiac
patients after non-cardiac surgeries. EVIDENCE ACQUISITION: A Meta-analysis about
the effect of anesthesia methods on postoperative MACEs and mortality in high
risk cardiac patients undergoing intermediate- or high-risk non-cardiac surgeries
was conducted; Chinese databases (SinoMed, CNKI, Wanfang, and VIP) and English
databases (Medline, EMBASE, PubMed, Springer, Ovid, the Cochrane Library, and
Google scholar) were searched. EVIDENCE SYNTHESIS: Twenty-seven randomized
controlled trials (RCTs) were included and 35340 patients were involved. The
cardiac troponin I level (cTnI) on postoperative day 1 (MD: -0.39, 95% CI: -0.45-
0.34, P<0.00001) and the incidence of myocardial ischaemia (OR: 0.43, 95% CI:
0.27-0.68, P=0.0004) within 3 postoperative days were significantly lower after
sevoflurane anesthesia than propofol anesthesia. There were no differences in
postoperative MACEs or in mortality within either 30 days or 1 year between
sevoflurane and propofol anesthesia, or between N2O and non-N2O anesthesia. The
cTnI on postoperative day 3 was significantly lower from epidural anesthesia
combined with general anesthesia (GA) than from GA alone (MD: -0.61, 95% CI:
0.75--0.47, P<0.00001). However, there were no differences in myocardial
infarction or mortality between epidural anesthesia combined with GA and GA
alone, or between spinal anesthesia alone and GA alone. CONCLUSIONS: Sevoflurane
anesthesia, or epidural combined with general anesthesia can provide short-term
myocardial protective effect in high-risk cardiac patients undergoing
intermediate- or high-risk non-cardiac surgeries.
PMID- 28402095
TI - Airway management and the unstable cervical spine: it is time to assess outcomes
that matter to patients.
PMID- 28402096
TI - Ecological implications of different antibiotic strategies in the management of
ventilator-associated pneumonia: in medio stat virtus.
PMID- 28402097
TI - The last sigh and the death knell: a view on lung hyperinflation from a
millennium ago.
PMID- 28402098
TI - Novel Multilayer Nanostructured Materials for Recognition of Polycyclic Aromatic
Sulfur Pollutants and Express Analysis of Fuel Quality and Environmental Health
by Surface Enhanced Raman Spectroscopy.
AB - A novel concept of advanced SERS (surface enhanced Raman spectroscopy) planar
sensors is suggested for fast analysis of sulfur-containing hazardous oil
components and persistent pollutants. The main advantage of the proposed sensors
is the utilization of an additional preconcentrating layer of optically
transparent chitosan gel, which is chemically modified with appropriate pi
acceptor compounds to selectively form charge-transfer complexes (CTCs) at the
interface with nanostructured silver coatings. The CTCs shift absorption bands of
polycyclic aromatic sulfur heterocycles (PASHs) and other important analytes in a
controllable way and thus provide a surplus enhancement of vibration modes due to
resonant Raman scattering. This novel indicator system provides multiplex
determination of PASHs in different forms in a small volume of oil without any
tedious sample pretreatment steps. This approach opens new possibilities of
increasing either spectral and concentration sensitivity or specificity of SERS
based sensors, allowing for new developments in the fields of ecology, advanced
fuel analysis, and other prospective applications.
PMID- 28402099
TI - Decreasing the Wettability of Cellulose Nanocrystal Surfaces Using Wrinkle-Based
Alignment.
AB - Cellulose nanocrystals (CNCs) are a particularly appealing format of the natural
biopolymer due to their exceptional strength, nanoscale dimensions, and needle
like shape anisotropy. However, CNCs are hydrophilic and hence their wettability
makes them impractical for many coating applications, with various approaches
using chemical functionalization to overcome this. Here we show that CNC-coated
surfaces can be rendered hydrophobic by alignment of the native CNCs using a
wrinkled template-mediated printing process. We present a novel and simple method
allowing full release of the CNCs from the template and their permanent
adsorption into fine patterns onto the surface, thus preventing CNC repositioning
during wetting. The aligned CNCs induce strong pinning effects that capture and
retain water droplets with high contact angle and large roll-off angles, without
becoming susceptible to oil contamination. The fabrication process for these
coatings could be achieved by large-scale printing, making them a practical and
cost-effective solution to hydrophobic coatings from raw cellulosic materials.
PMID- 28402100
TI - Structural Studies Revealed Active Site Distortions of Human Furin by a Small
Molecule Inhibitor.
AB - Proprotein convertases (PCs) represent highly selective serine proteases that
activate their substrates upon proteolytic cleavage. Their inhibition is a
promising strategy for the treatment of several pathologies including cancer,
atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present
the first experimental complex of furin with a non-substrate-like small molecule
inhibitor, and the X-ray structure of the enzyme complexed to the small molecule
inhibitor 1 at 1.9 A resolution. Two molecules of inhibitor 1 were found to
interact with furin. One is anchored at the S4 pocket of the enzyme and
interferes directly with the conformation and function of the catalytic triade;
the other molecule shows weaker binding and interacts with a distant, less
conserved region of furin. The observed binding modes represent a new inhibition
strategy of furin and imply the possibility to attain specificity among the PCs
providing an innovative starting point of structure guided inhibitor development
for furin.
PMID- 28402101
TI - Synergistically Enhanced Performance of Ultrathin Nanostructured Silicon Solar
Cells Embedded in Plasmonically Assisted, Multispectral Luminescent Waveguides.
AB - Ultrathin silicon solar cells fabricated by anisotropic wet chemical etching of
single-crystalline wafer materials represent an attractive materials platform
that could provide many advantages for realizing high-performance, low-cost
photovoltaics. However, their intrinsically limited photovoltaic performance
arising from insufficient absorption of low-energy photons demands careful design
of light management to maximize the efficiency and preserve the cost
effectiveness of solar cells. Herein we present an integrated flexible solar
module of ultrathin, nanostructured silicon solar cells capable of simultaneously
exploiting spectral upconversion and downshifting in conjunction with
multispectral luminescent waveguides and a nanostructured plasmonic reflector to
compensate for their weak optical absorption and enhance their performance. The 8
MUm-thick silicon solar cells incorporating a hexagonally periodic nanostructured
surface relief are surface-embedded in layered multispectral luminescent media
containing organic dyes and NaYF4:Yb3+,Er3+ nanocrystals as downshifting and
upconverting luminophores, respectively, via printing-enabled deterministic
materials assembly. The ultrathin nanostructured silicon microcells in the
composite luminescent waveguide exhibit strongly augmented photocurrent (~40.1
mA/cm2) and energy conversion efficiency (~12.8%) than devices with only a single
type of luminescent species, owing to the synergistic contributions from optical
downshifting, plasmonically enhanced upconversion, and waveguided photon flux for
optical concentration, where the short-circuit current density increased by ~13.6
mA/cm2 compared with microcells in a nonluminescent medium on a plain silver
reflector under a confined illumination.
PMID- 28402102
TI - High-Performance Piezoresistive Electronic Skin with Bionic Hierarchical
Microstructure and Microcracks.
AB - Electronic skin (E-skin), a popular research topic at present, has achieved
significant progress in a variety of sophisticated applications. However, the
poor sensitivity and stability severely limit the development of its application.
Here, we present a facile, cost-effective, and scalable method for manufacturing
E-skin devices with bionic hierarchical microstructure and microcracks. Our
devices exhibit high sensitivity (10 kPa-1) and excellent durability (10 000
cycles). The synergistic enhancement mechanism of the hierarchical microstructure
and the microcracks on the conductive layers was discovered. Moreover, we carried
out a series of studies on the airflow detection and the noncontact speech
recognition.
PMID- 28402103
TI - Patient-Derived Airway Secretion Dissociation Technique To Isolate and
Concentrate Immune Cells Using Closed-Loop Inertial Microfluidics.
AB - Assessment of airway secretion cells, both for research and clinical purposes, is
a highly desired goal in patients with acute and chronic pulmonary diseases.
However, lack of proper cell isolation and enrichment techniques hinder
downstream evaluation and characterization of cells found in airway secretions.
Here, we demonstrate a novel enrichment method to capture immune-related cells
from clinical airway secretions using closed-loop separation of spiral inertial
microfluidics (C-sep). By recirculating the output focusing stream back to the
input reservoir and running continuously with a high flow processing rate, one
can achieve optimal concentration, recovery and purity of airway immune cells
from a large volume of diluent, which was not readily possible in the single-pass
operation. Our method reproducibly recovers 94.0% of polymorphonuclear leukocytes
(PMNs), with up to 105 PMNs in clear diluted buffer from 50 MUL of airway
secretions obtained from mechanically ventilated patients. We show that C-sep
isolated PMNs show higher neutrophil elastase (NE) release following activation
by phorbol 12-myristate 13-acetate (PMA) than cells isolated by conventional
mucolytic method. By capturing cells without chemically disrupting their
potential function, our method is expected to expand the possibility of clinical
in vitro cell based biological assays for various pulmonary diseases such as
acute respiratory distress syndrome, pneumonia, cystic fibrosis, and
bronchiectasis.
PMID- 28402105
TI - Tin Selenides with Layered Crystal Structures for Li-Ion Batteries: Interesting
Phase Change Mechanisms and Outstanding Electrochemical Behaviors.
AB - Tin selenides with layered crystal structures, SnSe and SnSe2, were synthesized
by a solid-state method and electrochemically tested for use as Li-ion battery
anodes. The phase change mechanisms of these compounds were thoroughly evaluated
by ex situ X-ray diffraction and Se K-edge extended X-ray absorption fine
structure techniques. SnSe showed better electrochemical reversibility of Li
insertion/extraction than SnSe2, which was attributed to remarkable
conversion/recombination reactions of the former compound during
lithiation/delithiation. Additionally, the electrochemical performance of SnSe
was further enhanced by preparing carbon-modified nanocomposites using two
different methods, that is, heat treatment (HT) for producing a carbon coating
using polyvinyl chloride as a precursor and high-energy ball milling (BM) using
carbon black powder. The SnSe/C electrode produced by BM showed a highly
reversible initial capacity of 726 mA h g-1 with a good initial Coulombic
efficiency of ~82%, excellent cycling behavior (626 mA h g-1 after 200 cycles),
and a fast C-rate performance (580 mA h g-1 at 2C rate).
PMID- 28402106
TI - Reply to Comment on "Monitoring Network and Interfacial Healing Processes by
Broadband Dielectric Spectroscopy: A Case Study on Natural Rubber".
PMID- 28402104
TI - Hydrogen/Deuterium Exchange Mass Spectrometry of Human Green Opsin Reveals a
Conserved Pro-Pro Motif in Extracellular Loop 2 of Monostable Visual G Protein
Coupled Receptors.
AB - Opsins comprise the protein component of light sensitive G protein-coupled
receptors (GPCRs) in the retina of the eye that are responsible for the
transduction of light into a biochemical signal. Here, we used hydrogen/deuterium
(H/D) exchange coupled with mass spectrometry to map conformational changes in
green cone opsin upon light activation. We then compared these findings with
those reported for rhodopsin. The extent of H/D exchange in green cone opsin was
greater than in rhodopsin in the dark and bleached states, suggesting a higher
structural heterogeneity for green cone opsin. Further analysis revealed that
green cone opsin exists as a dimer in both dark (inactive) and bleached (active)
states, and that the predicted glycosylation sites at N32 and N34 are indeed
glycosylated. Comparison of deuterium uptake between inactive and active states
of green cone opsin also disclosed a reduced solvent accessibility of the
extracellular N-terminal region and an increased accessibility of the chromophore
binding site. Increased H/D exchange at the extracellular side of transmembrane
helix four (TM4) combined with an analysis of sequence alignments revealed a
conserved Pro-Pro motif in extracellular loop 2 (EL2) of monostable visual GPCRs.
These data present new insights into the locus of chromophore release at the
extracellular side of TM4 and TM5 and provide a foundation for future functional
evaluation.
PMID- 28402107
TI - Robust and Low-Cost Flame-Treated Wood for High-Performance Solar Steam
Generation.
AB - Solar-enabled steam generation has attracted increasing interest in recent years
because of its potential applications in power generation, desalination, and
wastewater treatment, among others. Recent studies have reported many strategies
for promoting the efficiency of steam generation by employing absorbers based on
carbon materials or plasmonic metal nanoparticles with well-defined pores. In
this work, we report that natural wood can be utilized as an ideal solar absorber
after a simple flame treatment. With ultrahigh solar absorbance (~99%), low
thermal conductivity (0.33 W m-1 K-1), and good hydrophilicity, the flame-treated
wood can localize the solar heating at the evaporation surface and enable a solar
thermal efficiency of ~72% under a solar intensity of 1 kW m-2, and it thus
represents a renewable, scalable, low-cost, and robust material for solar steam
applications.
PMID- 28402108
TI - Radical Borylation/Cyclization Cascade of 1,6-Enynes for the Synthesis of Boron
Handled Hetero- and Carbocycles.
AB - A synthetic method to construct boron-handled cyclic molecules was developed
based on a radical borylation/cyclization cascade of 1,6-enynes. The process was
initiated by the chemo- and regio-controlled addition of an N-heterocyclic
carbene-boryl radical to an alkene or alkyne, followed by ring closure to afford
boron-substituted cyclic skeletons. Further molecular transformations of the
cyclic products to synthetically useful building blocks were also demonstrated.
PMID- 28402109
TI - Merging Photoredox with 1,2-Metallate Rearrangements: The Photochemical
Alkylation of Vinyl Boronate Complexes.
AB - Vinyl boronates react with electron-deficient alkyl iodides in the presence of
visible light to give boronic esters in which two new C-C bonds have been
created. The reaction occurs by radical addition of an electron-deficient alkyl
radical to the vinyl boronate followed by electron transfer with another molecule
of alkyl iodide, continuing the chain, and triggering a 1,2-metalate
rearrangement. In a number of cases, the use of a photoredox catalyst enhances
yields significantly. The scope of the radical precursor includes alpha-iodo
ketones, esters, nitriles, primary amides, alpha-fluorinated halo-acetates and
perfluoroalkyl iodides.
PMID- 28402110
TI - A Molecular Perovskite with Switchable Coordination Bonds for High-Temperature
Multiaxial Ferroelectrics.
AB - The underlying phase transitions of ferroelectric mechanisms in molecular
crystals are mainly limited to order-disorder and displacive types that are not
involved in breaking of the chemical bonds. Here, we show that the bond-switching
transition under ambient pressure is designable in molecular crystals, and
demonstrate how to utilize the weaker and switchable coordination bonds in a
novel molecular perovskite, [(CH3)3NOH]2[KFe(CN)6] (TMC-1), to afford a scarce
multiaxial ferroelectrics with a high Curie temperature of 402 K and 24
equivalent ferroelectric directions (more than BaTiO3). The high-quality thin
films of TMC-1 can be easily fabricated by a simple solution process, and to
reveal perfect ferroelectric properties at both macroscopic and microscopic
scales, suggesting TMC-1 as a promising candidate for applications in next
generation flexible electronics. The presented molecular assembly strategy,
together with the achieved bond-switching ferroelectric mechanism, opens a new
avenue for designing advanced ferroelectric materials.
PMID- 28402111
TI - Permeable Self-Assembled Molecular Containers for Catalyst Isolation Enabling Two
Step Cascade Reactions.
AB - Establishment of a general one-pot cascade reaction protocol would dramatically
reduce the effort of multistep organic synthesis. We demonstrate that the unique
structure of M12L24 self-assembled complexes gives them the potential to serve as
catalyst carriers for enabling continuous chemical transformations. A
stereoselective cascade reaction (allylic oxidation followed by Diels-Alder
cyclization) with two intrinsically incompatible catalysts was demonstrated. Our
system is advantageous in terms of availability, scalability, and predictability.
PMID- 28402112
TI - Self-Assembled Upconversion Nanoparticle Clusters for NIR-controlled Drug Release
and Synergistic Therapy after Conjugation with Gold Nanoparticles.
AB - Fabricated three-dimensional (3D) upconversion nanoclusters (abbreviated as
EBSUCNPs) are obtained via an emulsion-based bottom-up self-assembly of
NaGdF4:Yb/Er@NaGdF4 nanoparticles (abbreviated as UCNPs), which comprise a
NaGdF4:Yb/Er core and a NaGdF4 shell. The EBSUCNPs were then coated with a thin
mesoporous amino-functionalized SiO2 shell (resulting in EBSUCNPs@SiO2 precursor)
and further conjugated with gold nanoparticles to give the novel EBSUCNPs@SiO2@Au
material. Finally, EBSUCNPs@SiO2@Au was applied as a biocompatible and efficient
drug carrier for doxorubicin (DOX), thus giving rise to a multifunctional
EBSUCNPs@SiO2-DOX@Au nanocomposite. This final material, EBSUCNPs@SiO2-DOX@Au,
and the precursor nanoparticles, EBSUCNPs@SiO2@Au, were both fully characterized
and their luminescence was investigated in detail. In addition, the drug release
properties and photothermal effects of EBSUCNPs@SiO2-DOX@Au were also discussed.
Interestingly, when under NIR irradiation, an increasing DOX release was achieved
owing to the thermal effect of the Au NPs after absorbing the green light from
the upconversion nanoclusters based on the fluorescence resonance energy transfer
(FRET) effect. Thus, a near-infrared (NIR)-controlled "on-off" pattern of drug
release behavior can be achieved. Moreover, compared with a single therapy
method, the assembled nanocomposites exhibit a good synergistic therapy against
cancer cells that combines chemotherapy with photothermal therapy. In addition,
the in vitro fluorescence microscopy images of EBSUCNPs@SiO2-DOX@Au show a higher
enhancement in the red region due to the loading of DOX molecules with respect to
EBSUCNPs@SiO2@Au. Therefore, this novel multifunctional 3D cluster architecture
can be used in the biomedical field after modification and may pave a new way in
other application areas of UCNPs clusters.
PMID- 28402113
TI - Importance of the Kinetic Energy Density for Band Gap Calculations in Solids with
Density Functional Theory.
AB - Recently, exchange-correlation potentials in density functional theory were
developed with the goal of providing improved band gaps in solids. Among them,
the semilocal potentials are particularly interesting for large systems since
they lead to calculations that are much faster than with hybrid functionals or
methods like GW. We present an exhaustive comparison of semilocal exchange
correlation potentials for band gap calculations on a large test set of solids,
and particular attention is paid to the potential HLE16 proposed by Verma and
Truhlar. It is shown that the most accurate potential is the modified Becke
Johnson potential, which, most noticeably, is much more accurate than all other
semilocal potentials for strongly correlated systems. This can be attributed to
its additional dependence on the kinetic energy density. It is also shown that
the modified Becke-Johnson potential is at least as accurate as the hybrid
functionals and more reliable for solids with large band gaps.
PMID- 28402114
TI - Characterization and Modeling of Polycyclic Aromatic Compound Uptake into Spruce
Tree Wood.
AB - This study highlights the potential of uptake into tree inner wood via direct
transfer through bark, as one contributing mechanism to describe atmospheric
uptake of polycyclic aromatic compounds (PACs) into trees. The uptake of PACs
into blue spruce tree wood was measured, with wood-air partition coefficients
(KWOOD_AIR) determined for five PACs. A correlation between the octanol-air
partition coefficient (KOA) and KWOOD_AIR for these five chemicals was determined
and the KWOOD_AIR for 43 PACs were derived. A ratio of solubility (activity)
difference between tree wood and octanol was also determined for these chemicals
from this correlation. Finally, the derived KWOOD_AIR values were further applied
to calculate an air volume sampled by the inner wood layer (cambium) of a tree
during a one year growth (sampling) period. PACs with a log KWOOD_AIR > 6
remained in the linear sampling phase over one year of sampling. The results
further highlight the important sink that forests provide for atmospheric organic
chemicals which should be considered for emissions monitoring and impact
assessments from destructive events such as forest fires or clear felling of
forests.
PMID- 28402115
TI - Hole Transfer Processes in meta- and para-Conjugated Mixed Valence Compounds:
Unforeseen Effects of Bridge Substituents and Solvent Dynamics.
AB - To address the question whether donor substituents can be utilized to accelerate
the hole transfer (HT) between redox sites attached in para- or in meta-positions
to a central benzene bridge, we investigated three series of mixed valence
compounds based on triarylamine redox centers that are connected to a benzene
bridge via alkyne spacers at para- and meta-positions. The electron density at
the bridge was tuned by substituents with different electron donating or
accepting character. By analyzing optical spectra and by DFT computations we show
that the HT properties are independent of bridge substituents for one of the meta
series, while donor substituents can strongly decrease the intrinsic barrier in
the case of the para-series. In stark contrast, temperature-dependent ESR
measurements demonstrate a dramatic increase of both the apparent barrier and the
rate of HT for strong donor substituents in the para-cases. This is caused by an
unprecedented substituent-dependent change of the HT mechanism from that
described by transition state theory to a regime controlled by solvent dynamics.
For solvents with slow longitudinal relaxation (PhNO2, oDCB), this adds an
additional contribution to the intrinsic barrier via the dielectric relaxation
process. Attaching the donor substituents to the bridge at positions where the
molecular orbital coefficients are large accelerates the HT rate for meta
conjugated compounds just as for the para-series. This effect demonstrates that
the para-meta paradigm no longer holds if appropriate substituents and
substitution patterns are chosen, thereby considerably broadening the
applicability of meta-topologies for optoelectronic applications.
PMID- 28402116
TI - Nickel-Catalyzed Direct Synthesis of Aryl Olefins from Ketones and Organoboron
Reagents under Neutral Conditions.
AB - Nickel-catalyzed addition of arylboron reagents to ketones results in aryl
olefins directly. The neutral condition allows acidic protons of alcohols,
phenols, and malonates to be present, and fragile structures are also tolerated.
PMID- 28402117
TI - Development of a One-Pot Synthetic Method for Multifunctional Oxazole Derivatives
Using Isocyanide Dichloride.
AB - A one-pot synthetic method was developed for multifunctional dihydrooxazole and
oxazole derivatives. New reaction sequences were developed involving the
formation of isocyanide dichloride, an aldol-type reaction with aldehydes, and a
nucleophilic addition-elimination reaction, which efficiently afforded the
dihydrooxazole and oxazole scaffolds.
PMID- 28402118
TI - Ultrafast Plasmon-Enhanced Hot Electron Generation at Ag Nanocluster/Graphite
Heterojunctions.
AB - Hot electron processes at metallic heterojunctions are central to optical-to
chemical or electrical energy transduction. Ultrafast nonlinear photoexcitation
of graphite (Gr) has been shown to create hot thermalized electrons at
temperatures corresponding to the solar photosphere in less than 25 fs. Plasmonic
resonances in metallic nanoparticles are also known to efficiently generate hot
electrons. Here we deposit Ag nanoclusters (NC) on Gr to study the ultrafast hot
electron generation and dynamics in their plasmonic heterojunctions by means of
time-resolved two-photon photoemission (2PP) spectroscopy. By tuning the
wavelength of p-polarized femtosecond excitation pulses, we find an enhancement
of 2PP yields by 2 orders of magnitude, which we attribute to excitation of a
surface-normal Mie plasmon mode of Ag/Gr heterojunctions at 3.6 eV. The 2PP
spectra include contributions from (i) coherent two-photon absorption of an
occupied interface state (IFS) 0.2 eV below the Fermi level, which electronic
structure calculations assign to chemisorption-induced charge transfer, and (ii)
hot electrons in the pi*-band of Gr, which are excited through the coherent
screening response of the substrate. Ultrafast pump-probe measurements show that
the IFS photoemission occurs via virtual intermediate states, whereas the
characteristic lifetimes attribute the hot electrons to population of the pi*
band of Gr via the plasmon dephasing. Our study directly probes the mechanisms
for enhanced hot electron generation and decay in a model plasmonic
heterojunction.
PMID- 28402119
TI - Impact of Electrolyte on Adsorption at the Air-Water Interface for Ternary
Surfactant Mixtures above the Critical Micelle Concentration.
AB - The composition of the air-water adsorbed layer of the ternary surfactant
mixture, octaethylene monododecyl ether, C12E8, sodium dodecyl 6
benzenesulfonate, LAS, and sodium dioxyethylene glycol monododecyl sulfate, SLES,
and of each of the binary mixtures, with varying amounts of electrolyte, has been
studied by neutron reflectivity. The measurements were made above the mixed
critical micelle concentration. In the absence of electrolyte adsorption is
dominated by the nonionic component C12E8 but addition of electrolyte gradually
changes this so that SLES and LAS dominate at higher electrolyte concentrations.
The composition of the adsorbed layer in both binary and ternary mixtures can be
quantitatively described using the pseudo-phase approximation with quadratic and
cubic interactions in the excess free energy of mixing (GE) at both the surface
and in the micelles. A single set of parameters fits all the experimental data. A
similar analysis is effective for a mixture in which SDS replaces SLES. Addition
of electrolyte weakens the synergistic SLES-C12E8 and LAS-C12E8 interactions,
consistent with them being dominated by electrostatic interactions. The SLES-LAS
(and SDS-LAS) interaction is moderately strong at the surface and is little
affected by addition of electrolyte, suggesting that it is controlled by
structural or packing factors. Most of the significant interactions in the
mixtures are unsymmetrical with respect to composition, with the minimum in GE at
the 1:2 or 2:1 composition. There is a small structural contribution to the LAS
C12E8 interaction that leads to a minimum intermediate in composition between 1:2
and 1:1 (LAS:C12E8) and to a significant residual GE in strong electrolyte.
PMID- 28402120
TI - Quantifying Electron Correlation of the Chemical Bond.
AB - The Interacting Quantum Atoms (IQA) method is used to analyze the correlated part
of the Moller-Plesset (MP) perturbation theory two-particle density matrix. Such
an analysis determines the effects of electron correlation within atoms and
between atoms, which covers both bonds and nonbonded through-space atom-atom
interactions within a molecule or molecular complex. Electron correlation lowers
the energy of the atoms at either end of a bond, but for the bond itself, it can
be stabilizing or destabilizing. Bonds are described in a two-dimensional world
of exchange and charge transfer, where covalency is not the opposite of ionicity.
PMID- 28402121
TI - In Situ Underwater Laser-Induced Breakdown Spectroscopy Analysis for Trace Cr(VI)
in Aqueous Solution Supported by Electrosorption Enrichment and a Gas-Assisted
Localized Liquid Discharge Apparatus.
AB - Traditional laser-induced breakdown spectroscopy (LIBS) always fails to directly
detect target in aqueous solution due to rapid quenching of emitted light and
adsorption of pulse energy by surrounding water. A method is proposed for the in
situ underwater LIBS analysis of Cr(VI) in aqueous solution freed from the common
problems mentioned above by combining a gas-assisted localized liquid discharge
apparatus with electrosorption for the first time. In this approach, the
introduction of the gas-assisted localized liquid discharge apparatus provides an
instantaneous gaseous environment for underwater LIBS measurement (that is, the
transfer of sampling matrix is not needed from aqueous solution to dry state).
The preconcentration of Cr(VI) is achieved by electrosorption with a positive
potential applied around adsorbents, which can promote the adsorption of Cr(VI)
and inhibit that of the coexisting cations leading to a good anti-interference.
Amino groups functionalized chitosan-modified graphene oxide (CS-GO) is utilized
for Cr(VI) enrichment, which can be protonated to form NH3+ in acidic condition
promoting the adsorption toward Cr(VI) by electrostatic attraction. The highest
detection sensitivity of 5.15 counts MUg-1 L toward Cr(VI) is found for the
optimized electrosorption potential (EES = 1.5 V) and electrosorption time (tES =
600 s) without interference from coexisting metal ions. A corresponding limit of
detection (LOD) of 12.3 MUg L-1 (3sigma method) is achieved, which is amazingly
improved by 2 or even 3 orders of magnitude compared to the previous reports of
LIBS.
PMID- 28402122
TI - Structure and Spectroscopy of C2HNO Isomers.
AB - Formyl cyanide has been detected toward Sgr B2 making this chemical and its
potential isomers of astrophysical interest. We calculated the precise energies
of the five most stable structural isomers of formyl cyanide and found that
formyl isocyanide and 2H-azirin-2-one are less stable than formyl cyanide by 55
and 125 kJ/mol, respectively. We present our ab initio coupled cluster
predictions of the spectroscopic parameters relevant to their gas-phase
rotational and vibrational spectroscopy. Parameters include ground vibrational
state rotational constants, centrifugal distortion parameters, equilibrium
electric dipole moments, and nuclear quadrupole coupling constants. Anharmonic
vibrational frequencies together with infrared intensities of fundamental and
nonfundamental modes were also calculated. The broader potential energy surface,
including transition states and the minima they connect, were explored for these
isomers at the B3LYP/aug-cc-pVTZ level of theory. Formyl cyanide can dissociate
in an exothermic reaction to form HCN and CO or in an endothermic reaction to
form HNC and CO. The activation energies for both processes are close to 260
kJ/mol. The activation barrier for conversion of formyl cyanide into formyl
isocyanide is ~180 kJ/mol. The energetic barrier for the exothermic decomposition
of formyl isocyanide into HNC and CO is ~210 kJ/mol. The barrier for
transformation of formyl isocyanide into formyl cyanide is ~130 kJ/mol. Formyl
isocyanide seems to be a stable chemical and could potentially survive in a dense
molecular cloud if formed. These data are useful for future identification of
members of this family of molecules in a laboratory or in space.
PMID- 28402123
TI - Iron Isotope Fractionation during Fe(II) Oxidation Mediated by the Oxygen
Producing Marine Cyanobacterium Synechococcus PCC 7002.
AB - In this study, we couple iron isotope analysis to microscopic and mineralogical
investigation of iron speciation during circumneutral Fe(II) oxidation and
Fe(III) precipitation with photosynthetically produced oxygen. In the presence of
the cyanobacterium Synechococcus PCC 7002, aqueous Fe(II) (Fe(II)aq) is oxidized
and precipitated as amorphous Fe(III) oxyhydroxide minerals (iron precipitates,
Feppt), with distinct isotopic fractionation (epsilon56Fe) values determined from
fitting the delta56Fe(II)aq (1.790/00 and 2.150/00) and the delta56Feppt
(2.440/00 and 2.980/00) data trends from two replicate experiments. Additional
Fe(II) and Fe(III) phases were detected using microscopy and chemical extractions
and likely represent Fe(II) and Fe(III) sorbed to minerals and cells. The iron
desorbed with sodium acetate (FeNaAc) yielded heavier delta56Fe compositions than
Fe(II)aq. Modeling of the fractionation during Fe(III) sorption to cells and
Fe(II) sorption to Feppt, combined with equilibration of sorbed iron and with
Fe(II)aq using published fractionation factors, is consistent with our resulting
delta56FeNaAc. The delta56Feppt data trend is inconsistent with complete
equilibrium exchange with Fe(II)aq. Because of this and our detection of
microbially excreted organics (e.g., exopolysaccharides) coating Feppt in our
microscopic analysis, we suggest that electron and atom exchange is partially
suppressed in this system by biologically produced organics. These results
indicate that cyanobacteria influence the fate and composition of iron in sunlit
environments via their role in Fe(II) oxidation through O2 production, the
capacity of their cell surfaces to sorb iron, and the interaction of secreted
organics with Fe(III) minerals.
PMID- 28402124
TI - Percutaneous radiofrequency ablation of hepatocellular carcinoma in cirrhosis:
analysis of complications in a single centre over 20 years.
AB - OBJECTIVE: To report on our 20 years' experience on complications after
radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in patients with
cirrhosis. METHODS: From 1994 to 2014, 1787 RFA procedures were performed
percutaneously in 1162 patients with cirrhosis (852 Child A and 310 Child B) with
HCC nodules (1.2-7 cm), prothrombin time >50%, platelet count of 50.000 mm3 and
total bilirubin ranging from 0.80 to 4.5 mg dl-1. In 67 patients, RFA was
performed on both intraparenchymal HCC nodule and tumour thrombus extended in the
main portal vein and/or its branches. RESULTS: Four patients (0.3%) died after
RFA. 39 patients (3.2%) changed in Child's class: 26 out of 28 Child A patients
with cirrhosis changed to Child B and 2 changed to Child C class; 11 Child B
patients changed to Child C class. On multivariate analysis, the total bilirubin
pre-RFA was the only independent risk factor for impairment of liver function and
death. Complications were hemoperitoneum, abscess and intrahepatic haematoma.
CONCLUSION: RFA of HCC in patients with cirrhosis is safe, even in case of
invasion of the portal venous system. Functional liver reserve should be strictly
monitored, mainly when pre-RFA total bilirubin value is >2.5 mg dl-1. The study
was approved by our institutional review board. Advances in knowledge: The total
bilirubin value >2.5 mg dl-1 represents the main marker of functional liver
reserve that predicts decompensation of liver cirrhosis in patients undergoing
RFA for HCC.
PMID- 28402125
TI - Assessment of radiation dose from abdominal quantitative CT with short scan
length.
AB - OBJECTIVE: To assess radiation dose for patients who received abdominal
quantitative CT and to compare the midpoint dose [DL(0)] at the centre of a 1-cm
scan length with the volume CT dose index (CTDIvol). Although the size-specific
dose estimate (SSDE) proposed in The American Association of Physicists in
Medicine Report No. 204 is not applicable for short-length scans, commercial dose
monitoring software, such as RadimetricsTM Enterprise Platform (Bayer HealthCare,
Whippany, NJ), reports SSDE for all scans. SSDE was herein compared with DL(0).
METHODS: Data were analyzed from 398 abdominal quantitative CT examinations in
165 males and 233 females. The CTDIvol was 4.66 mGy, and the scan length was 1 cm
for all examinations. Radimetrics was used to extract patient diameter and SSDE.
DL(0) was assessed using a previously reported method that takes into account
both patient size and scan length. RESULTS: The mean patient diameter was 28.5 +/
6.3 cm (range, 16.5-46.6 cm); the mean SSDE was 6.22 +/- 1.36 mGy (range, 3.12
9.42 mGy); and the mean DL(0) was 2.97 +/- 0.95 mGy (range, 1.18-5.77 mGy). As
patient diameter increased, the DL(0) to CTDIvol ratio decreased, ranging from
1.24 to 0.25; the DL(0) to SSDE ratio also decreased, ranging from 0.61 to 0.38.
CONCLUSION: The dose to the patients from abdominal quantitative CT may be
largely different from CTDIvol and SSDE. This study demonstrates the necessity of
taking into account not only patient size but also scan length for evaluating the
dose from short-length scans. Advances in knowledge: In CT examinations with 1-cm
scan length, dose evaluation needs to take into account both patient size and
scan length. An omission of either factor can result in an erroneous result.
PMID- 28402127
TI - Plagiarism in Manuscripts Submitted to the AJR: Development of an Optimal
Screening Algorithm and Management Pathways.
PMID- 28402126
TI - Implementation of a Point-of-Care Radiologist-Technologist Communication Tool in
a Quality Assurance Program.
AB - OBJECTIVE: We implemented an Image Quality Reporting and Tracking Solution
(IQuaRTS), directly linked from the PACS, to improve communication between
radiologists and technologists. MATERIALS AND METHODS: IQuaRTS launched in May
2015. We compared MRI issues filed in the period before IQuaRTS implementation
(May-September 2014) using a manual system with MRI issues filed in the IQuaRTS
period (May-September 2015). The unpaired t test was used for analysis. For
assessment of overall results in the IQuaRTS period alone, all issues filed
across all modalities were included. Summary statistics and charts were generated
using Excel and Tableau. RESULTS: For MRI issues, the number of issues filed
during the IQuaRTS period was 498 (2.5% of overall MRI examination volume)
compared with 78 issues filed during the period before IQuaRTS implementation
(0.4% of total examination volume) (p = 0.0001), representing a 625% relative
increase. Tickets that documented excellent work were 8%. Other issues included
images not pushed to PACS (20%), film library issues (19%), and documentation or
labeling (8%). Of the issues filed, 55% were MRI-related and 25% were CT-related.
The issues were stratified across six sites within our institution. Staff
requiring additional training could be readily identified, and 80% of the issues
were resolved within 72 hours. CONCLUSION: IQuaRTS is a cost-effective online
issue reporting tool that enables robust data collection and analytics to be
incorporated into quality improvement programs. One limitation of the system is
that it must be implemented in an environment where staff are receptive to
quality improvement.
PMID- 28402128
TI - Effects of skeletally anchored Class II elastics: A pilot study and new approach
for treating Class II malocclusion.
AB - OBJECTIVE: To evaluate the skeletal, dentoalveolar, and soft tissue effects of
skeletally anchored Class II elastics and compare them with a matched control
group treated by a monobloc appliance for the correction of skeletal Class II
malocclusion due to mandibular retrusion. MATERIALS AND METHODS: Twelve patients
(6 girls, 6 boys) were randomly divided into two groups. In the elastics group,
six patients (12.9 +/- 1.5 years of age; 3 boys, 3 girls) were treated with
skeletally anchored Class II elastics. Two miniplates were placed bilaterally at
the ramus of the mandible and the other two miniplates were placed at the
aperture piriformis area of the maxilla. In the monobloc group (3 boys and 3
girls; mean age, 12.3 +/- 1.6 years), patients used the monobloc appliance. The
changes observed in each phase of treatment were evaluated using the Wilcoxon
matched-pair sign test. Intergroup comparisons at the initial phase of treatment
were analyzed by the Mann-Whitney U test. RESULTS: There were statistically
significant group differences in Co-Gn, B-VRL, U1-PP, U1-VRL, Ls-VRL, with
significant increases in these parameters in the elastics group (P < .05). The
mandibular incisors were protruded in the monobloc group (5.45 +/- 1.23 degrees
), whereas they were retruded in the elastics group (-3.01 +/- 1.66 degrees ; P <
.01). CONCLUSIONS: The undesirable dentoalveolar effects of the monobloc
appliance were eliminated by using miniplate anchorage. Favorable skeletal
outcomes can be achieved by skeletal anchorage therapies which could be an
alternative to treat skeletal Class II patients with mandibular deficiency.
PMID- 28402130
TI - Hallway Conversations in PhysicsMRI Tractography: Mapping White Matter Tracts in
the Brain.
PMID- 28402129
TI - Consistency of Renal Stone Volume Measurements Across CT Scanner Model and
Reconstruction Algorithm Configurations.
AB - OBJECTIVE: The objective of this prospective study is to evaluate the consistency
of renal stone volume estimation using dual-energy CT across scanner model and
reconstruction algorithm configurations. SUBJECTS AND METHODS: Patients underwent
scanning with routine kidney stone composition protocols on both second- and
third-generation dual-source CT scanners. Images were reconstructed using
filtered back projection and iterative reconstruction (IR). In addition, a
modified IR kernel on the third-generation CT scanner was evaluated. Individual
kidney stone volumes were determined and compared. RESULTS: No significant
difference was noted in measured volumes between filtered back-projection data,
IR data from the second-generation scanner, and the modified IR kernel data (p >
0.05). The third-generation commercially available IR kernel yielded lower
volumes than did the other configurations (p < 0.0001). CONCLUSION: With the use
of a modified kernel for the third-generation scanner, patients being monitored
for changes in kidney stone volume can undergo scanning performed with second- or
third-generation dual-energy CT scanners, and the images obtained can be
reconstructed with either filtered back projection or IR without the introduction
of bias into kidney stone volume measurements.
PMID- 28402131
TI - Can Imaging Predict Subclinical Cortisol Secretion in Patients With Adrenal
Adenomas? A CT Predictive Score.
AB - OBJECTIVE: The aim of this study is to determine whether any correlation between
CT findings and functional parameters exists to predict subclinical
glucocorticoid secretion. MATERIALS AND METHODS: This is a retrospective database
study of 55 patients with incidentally discovered adenomas, investigated through
CT with an adrenal protocol, assessing diameters and attenuation values on the
unenhanced and contrast-enhanced phases. Patients underwent blood cortisol and
corticotropin evaluation and overnight dexamethasone suppression test (DST), in
accordance with clinical recommendations. Cortisol levels higher than 50 nmol/L
after DST identified subclinical cortisol secretion. We identified 28 subjects
with lipid-rich nonsecreting adenomas, nine with lipid-rich secreting adenomas,
11 with lipid-poor nonsecreting adenomas, and seven with lipid-poor secreting
adenoma. RESULTS: Cortisol levels after DST were significantly and positively
related to mass diameters. At univariate analysis, maximum and minimum diameters
and attenuation in the delayed phase were significantly related to the presence
of secreting or nonsecreting adenoma; at multivariate analysis, only the minimum
diameter and the attenuation in the venous phase entered the stepwise logistic
regression. Similarly, minimum diameter and attenuation in the venous phase
emerged also at the multivariate stepwise regression between radiologic
parameters and cortisol levels after DST. The formula of the radiologic score
computed by using the coefficients of the multivariate regression was as follows:
(0.1914 * minimum diameter) + (0.0308 * enhanced attenuation). The diagnostic
accuracy of this discriminatory score in differentiating secreting from
nonsecreting adenomas was 84.9%, the sensitivity was 81.3%, and the specificity
was 87.2%. Adenomas with scores greater than 7.59 were considered as secreting
adenomas, and adenomas with scores less than 7.36 were considered as nonsecreting
adenomas. CONCLUSION: This study shows that imaging parameters can predict
subclinical cortisol hypersecretion in patients with adrenal adenomas.
PMID- 28402132
TI - Modic Type 1 Vertebral Endplate Changes: Injury, Inflammation, or Infection?
AB - OBJECTIVE: In the 29 years since the initial description of Modic type 1
vertebral endplate changes there has been ongoing debate regarding their cause.
Studies have attributed Modic type 1 vertebral endplate changes to traumatic
injury to the vertebral endplate, localized action of proinflammatory mediators,
and more recently low-grade bacterial infection. Can we reconcile these
conflicting data about the underlying cause of Modic type 1 vertebral endplate
changes? Are we now in a position to conclude whether Modic type 1 vertebral
endplate changes are secondary to injury, inflammation, or infection? CONCLUSION:
We argue that the processes are not disparate but are in fact closely linked,
each potentially instigating a chain of events leading to the MRI findings of
Modic type 1 vertebral endplate change. A method of delineating which process is
predominantly at play in an individual patient is required so that tailored
treatment options can be offered with huge potential benefit to individuals and
society alike.
PMID- 28402134
TI - Cultivating the Therapeutic Self in China.
AB - Facing intensified market competition and rapid social change, many Chinese are
experiencing increased mental distress. In this article, I examine how
psychological training and interventions play a vital part in cultivating a new
self among urban middle-classes. I ask how the Chinese notion, ziwo (self), is
turned into an object of intense inquiry and how therapeutic techniques are
deployed for self-development. The new forms of the self, however, continue to
intersect with and complicate the existing social nexus, cultural sensibilities,
and notions of personhood. My ethnography explores how this therapeutic work
contributes to intricate forms of subject-making that challenge such conceptual
binaries as the private versus social self, the inner versus outer life, and
psychological versus social problems. Thus, what is emerging is not a usual
"neoliberalism" story of self-advancement, but a more complicated picture based
on assemblages.
PMID- 28402133
TI - JOURNAL CLUB: Structured Feedback From Patients on Actual Radiology Reports: A
Novel Approach to Improve Reporting Practices.
AB - OBJECTIVE: Patient perceptions of radiology reports are largely unknown. The
objective of the present study is to describe our experience receiving structured
feedback from patients on actual radiology reports as a means of improving
reporting practices. MATERIALS AND METHODS: Eight reports (two for radiographs,
two for ultrasound images, two for CT scans, and two for MR images) were randomly
selected from our system for review. For each report, patients were asked to rate
their level of comprehension, identify any problems in the report, and, in the
free-text portion of the feedback form, indicate any questions about the report
that they may have. Potentially confounding factors were also examined. RESULTS:
A total of 104 patients (46 men and 58 women) participated in the study (for a
total of 832 evaluations). The median score for report comprehension was 2.5 (on
a scale of 1-5), with the most common problems affecting comprehension identified
as "unclear or technical language" (mentioned in 59.6% of evaluations) and the
report being "too long" (mentioned in 10.2% of evaluations). A request for an
explanation of the report in lay terms (noted in 20.1% of evaluations) was the
most common request mentioned in the free-text portion of the feedback form. An
inverse relationship existed between report length and patient comprehension (p <
0.001). Patients who had prior experience with their own radiology reports
indicated having greater comprehension than did patients with no prior experience
(p = 0.003). No correlation between the educational status and report
comprehension of the patients was identified (p = 0.488). CONCLUSION: Radiology
reports are not well understood by patients, who identify technical language and
the long length of reports as the most common problems affecting their
comprehension. Longer reports tend to be less well understood.
PMID- 28402135
TI - Careful Words: Nursing, Language, and Emotion in Papua New Guinea.
AB - Papua New Guinean nurses work in a sociomedical system in which cultural and
linguistic diversity are matters of pressing concern. Using data drawn from
ethnographic research with PNG nursing students, I show how nursing education
socializes nurses to take stances toward language and communication that impact
their care practices. I argue that nurses' use of language is shaped by their
ethical commitments as educated Christians and indigenous concerns about the
links between language, emotion, and health. In a resource-poor setting where
health workers risk blame for structural inequalities, this "ethical
metapragmatics" is an important but neglected facet of care work.
PMID- 28402136
TI - Survey of discomfort glare from the headlamps of cars widely used in Iran.
AB - OBJECTIVE: On 2-lane roads, discomfort glare can cause annoyance, discomfort,
inconvenience, stress, and fatigue to drivers, posing a risk of accidents. The
aim of this study is to evaluate discomfort glare from the headlamps of cars
widely used in Iran. METHODS: The discomfort glare of new vehicles including
Pride Saba model GTX, Pride Model 131SL, Samand Soren, Peugeot 405, Megane, and
Peugeot Pars was examined at distances of 5 to 100 m at a background luminance of
50 cd/m2 (late twilight/early dawn lighting) and 1 cd/m2 (nighttime) using
Schmidt-Clausen and Bindels model and de Boer's subjective scale. RESULTS:
According to the de Boer scale, at a background luminance of 50 cd/m2, the
discomfort glare for all studied vehicles was between 1.98 and 4.05 in high-beam
mode and between 3.5 and 5.4 in low-beam mode. At a background luminance of 1
cd/m2, discomfort glare was between 0.41 and 2.48 in high-beam mode and between
1.93 and 3.84 in low-beam mode. In high-beam mode, the average levels of
discomfort glare of these vehicles gradually increased when the distance between
cars was reduced by up to about 20 m. In low-beam mode, there was no discomfort
glare up to a vehicle distance of 40 m. In addition, at an angle of 1.15 degrees
5.73 degrees between the line of sight and light of vehicles in high-beam mode,
the level of discomfort glare was increased, but at an angle of 5.73 degrees
22.9 degrees the level of discomfort glare was reduced. In low-beam mode at an
angle of 2.86 degrees -22.9 degrees , the level of discomfort glare was almost
identical. The results show that in high-beam mode and with a 100-m distance
between vehicles as well as in low-beam mode at intervals of less than 40 m
between cars, discomfort glare is created. CONCLUSION: It can be concluded that
by providing solutions such as installing road lighting system, an increase in
luminance of roads, separating or widening road lanes, increasing the lateral
distance between vehicles, and increasing the angle between lighted vehicles and
drivers can noticeably reduce discomfort glare.
PMID- 28402137
TI - Managing Meanings of Embodied Experiences Theory: Toward a Discursive
Understanding of Becoming Healthier.
AB - We advance a new theoretical approach for interpreting health communication from
an embodied, intersubjective perspective. We propose individuals experience the
world as bodied beings and must make sense of their embodied experiences by
managing meanings of who they are in the world (being), the actions they perform
(doing), and who they want to become (directed becoming). We call this theory
managing meanings of embodied experiences (MMEE). Guided by the philosophies of
phenomenology, pragmatism, and feminism, we provide a three-fold framework for
exploring individuals' management of health meanings during interactions with
others in society. The first layer-being-demonstrates a mutually constituting,
intersubjective presence with others, whereby we attend to our own and another's
embodied expressions accomplished communicatively. The second layer-doing
appreciates experiences directed by personal and social values both perceived and
conceived during the unfolding of coordinated communicative events. The third
layer-directed becoming-highlights our ability to mindfully direct changes to our
identity and actions through critical reflection; it is the transformative
potential of our reflective synthesis of being and doing.
PMID- 28402138
TI - Exploring Differences in Patient-Centered Practices among Healthcare
Professionals in Acute Care Settings.
AB - There is limited evidence of the extent to which Healthcare professionals
implement patient-centered care (PCC) and of the factors influencing their PCC
practices in acute care organizations. This study aimed to (1) examine the
practices reported by health professionals (physicians, nurses, social workers,
other healthcare providers) in relation to three PCC components (holistic,
collaborative, and responsive care), and (2) explore the association of
professionals' characteristics (gender, work experience) and a contextual factor
(caseload), with the professionals' PCC practices. Data were obtained from a
large scale cross-sectional study, conducted in 18 hospitals in Ontario, Canada.
Consenting professionals (n = 382) completed a self-report instrument assessing
the three PCC components and responded to standard questions inquiring about
their characteristics and workload. Small differences were found in the PCC
practices across professional groups: (1) physicians reported higher levels of
enacting the holistic care component; (2) physicians, other healthcare providers,
and social workers reported implementing higher levels of the collaborative care
component; and (3) physicians, nurses, and other healthcare providers reported
higher levels of providing responsive care. Caseload influenced holistic care
practices. Interprofessional education and training strategies are needed to
clarify and address professional differences in valuing and practicing PCC
components. Clinical guidelines can be revised to enable professionals to engage
patients in care-related decisions, customize patient care, and promote
interprofessional collaboration in planning and implementing PCC. Additional
research is warranted to determine the influence of professional, patient, and
other contextual factors on professionals' PCC practices in acute care hospitals.
PMID- 28402139
TI - Long-Term, Open-Label, Safety Study of Edivoxetine Monotherapy in Children and
Adolescents with Attention-Deficit/Hyperactivity Disorder.
AB - OBJECTIVE: The purpose of this study was to assess the long-term safety and
tolerability of edivoxetine, a selective norepinephrine reuptake inhibitor, which
was being developed as monotherapy in pediatric attention-deficit/hyperactivity
disorder (ADHD). METHODS: This was an open-label study of edivoxetine once daily
dosing (0.1-0.3 mg/kg) as treatment for ADHD in children (6-11 years) and
adolescents (12-17 years) to assess safety for up to 5 years. The safety
assessments included the incidence of adverse events, vital signs,
electrocardiograms, laboratory tests, percentile changes in weight, height, and
body mass index, and Tanner staging. Efficacy of treatment with edivoxetine was
also assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale
Version IV-Parent Reported: Investigator Scored (ADHDRS-IV) and Clinical Global
Impressions-ADHD-Severity (CGI-ADHD-S). RESULTS: A total of 267 children and
adolescents were enrolled and 20 completed the 5-year study. Most of the
participants were male (70.4%) and white (67.4%), and the mean age was 11.6
years. Two hundred three participants (76.9%; N = 264) experienced at least one
adverse event. Treatment-emergent adverse events reported in >10% of participants
were headache, vomiting, nausea, and upper respiratory tract infection. Serious
adverse events (SAEs) were reported by seven participants (2.7%) during study
treatment periods, and one participant was diagnosed with suspect epilepsy during
the follow-up period after discontinuation of edivoxetine. CONCLUSION: Long-term
open-label treatment with edivoxetine as monotherapy in children and adolescents
with ADHD revealed a safety profile that was consistent with its pharmacological
effects on norepinephrine transmission and with that reported in short-term
studies of edivoxetine. The study was terminated early due to slow enrollment and
the very low number of 5-year completers. Lilly is not proceeding with further
development of edivoxetine, as announced in 2013.
PMID- 28402140
TI - Reducing behavioural risk factors for cancer: An affect regulation perspective.
AB - Nearly half of all cancer deaths are attributable to preventable causes,
primarily unhealthy behaviours such as tobacco use, alcohol use and overeating.
In this review, we argue that people engage in these behaviours, at least in
part, as a means of regulating their affective states. To better understand why
people engage in these behaviours and how researchers might design interventions
to promote the selection of healthier methods for regulating affect, we propose a
conceptual model of affect regulation. We synthesise research from both the
stress and coping tradition as well as the emotion and emotion regulation
tradition, two literatures that are not typically integrated. In so doing, we
indicate where researchers have made headway in understanding these behaviours as
affect regulation and note how our model could be used to structure future work
in a way that would be particularly advantageous to cancer control efforts.
PMID- 28402141
TI - The Gobbledygook in Online Parent-Focused Information about Child and Adolescent
Mental Health.
AB - Online parent-focused informational resources play a vital step in parent
decision-making about initiating child and adolescent mental health care, but
their usefulness may depend on how easily the resource content can be understood.
The purpose of this cross-sectional study was to examine the readability and
reliability of parent-focused mental health resources provided on Canadian
websites. After meeting inclusion criteria, 50 documents retrieved during the
search in September 2016 from websites using online health information searching
strategies that would be typically employed by parents underwent analysis.
Document readability was assessed using Health Canada recommended instruments:
Simple Measure of Gobbledygook (SMOG), Flesch-Kincaid Grade Level, and the Flesch
Reading-Ease scale. Reliability was assessed using Health on the Net Foundation
Code of Conduct (HONcode). Our analysis revealed that all included documents
exceeded the 8th grade reading level. The mean +/- SD readability scores were
SMOG 11.65 +/- 1.10 and FKGL 10.03 +/- 1.49. Reading-ease scores showed that 42%
(n = 21) of the documents were "Difficult" to read. Factorial ANOVA revealed no
significant difference in readability across mental health topic areas or
organizational sectors (p = > 0.05). Twenty-four percent of documents came from
sites with HONcode certification. Findings suggest that almost all child and
adolescent mental health information that would typically be found online by
parents in Canada had readability scores that were too high for average parents
to read and exceeded Health Canada recommended reading levels. Being able to
locate resources online can be significantly precluded if a parent cannot
understand and use information to mobilize them to accessing mental health care
for their families.
PMID- 28402142
TI - Development of separation technology for the removal of radium-223 from targeted
thorium conjugate formulations. Part II: purification of targeted thorium
conjugates on cation exchange columns.
AB - Tumor targeting pharmaceuticals will play a crucial role in future pharma
pipelines. The targeted thorium conjugate (TTC) therapeutic platform could
provide real benefit to patients, whereby targeting moieties like monoclonal
antibodies are radiolabelled with the alpha-emitting radionuclide thorium-227
(227Th, t1/2 = 18.7 days). A potential problem could be the accumulation of the
long-lived daughter nuclide radium-223 (223Ra, t1/2 = 11.4 days) in the drug
product during manufacturing and distribution. Therefore, the level of 223Ra must
be standardized before administration to the patient. The focus in this study has
been the removal of 223Ra, as the other progenies will have a very limited stay
in the formulation. In this study, the purification of TTCs labeled with decayed
227Th has been explored. Columns packed with a strong cation exchange resin have
been used to sequester 223Ra. The separation of TTC from 223Ra has been evaluated
as influenced by both formulation and process parameters with a design of
experiments (DOE) study; including citrate or acetate buffer, pH, buffer
concentration, presence or absence of pABA + EDTA, resin amount and sodium
chloride concentration. The aim was to achieve a separation with high sorption of
223Ra and accompanying low TTC sorption. The results were analyzed by
multivariate analysis. Four regression models of TTC and 223Ra sorption from
citrate and acetate buffered formulations were developed. The predictive accuracy
of sorption in the four statistical models was given by standard deviations and
confidence intervals. The TTC sorption in citrate and acetate buffered
formulations was affected by the identical variables and the variation in TTC
sorption was comparable for the two models. However, the DOE variables had a
significantly stronger impact on the 223Ra sorption in citrate buffered
formulations than the 223Ra sorption in acetate buffer. An optimal separation
with a TTC sorption below 25% and 223Ra sorption above 90% can be achieved in
both citrate and acetate buffered formulations. Stability studies of
radiochemical purity (RCP) indicated that the measured 227Th values may be partly
due to free 227Th and not TTC, but the results indicate that TTC stability may be
controlled by optimizing formulation parameters. Hence, the sorption data and the
regression models presented must be reviewed and further explored with regard to
what is known about the stability of the TTC in the different buffered
formulations.
PMID- 28402143
TI - A pH-independent instantaneous release of flurbiprofen: a study of the
preparation of complexes, their characterization and in vitro/in vivo evaluation.
AB - In this study, furbiprofen/hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion
complexes were prepared to improve the drug dissolution and facilitate its
application in hydrophilic gels. Inclusion complexes were prepared using a
supercritical fluid processing and a conventional optimized co-lypholization
method was employed as a reference. The entrapment efficacy and drug loading of
both methods were investigated. Evaluation of drug dissolution enhancement was
conducted in deionized water as well as buffer solutions of different pH.
Carbopol 940 gels of both flurbiprofen and flurbiprofen/HPbetaCD inclusion
complexes, with or without penetration enhancers, were prepared and percutaneous
permeation studies were performed using rat abdominal skin samples. Formation of
flurbiprofen/HPbetaCD inclusion complexes was confirmed by Fourier transform
infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and
scanning electron microscopy. The results obtained showed that SCF processing
produced a higher EE (81.91 +/- 1.54%) and DL (6.96 +/- 0.17%) compared with OCL
with values of 69.11 +/- 2.23% and 4.00 +/- 1.01%, respectively. A marked
instantaneous release of flurbiprofen/HPbetaCD inclusion complexes prepared by
SCF processing (103.04 +/- 2.66% cumulative release within 5 min, a 10-fold
increase in comparison with flurbiprofen alone) was observed. In addition, this
improvement in dissolution was shown to be pH-independent (the percentage
cumulative release at pH 1.2, 4.5, 6.8 and 7.4 at 5 min was 95.19 +/- 1.71,
101.75 +/- 1.44, 105.37 +/- 4.58 and 96.84 +/- 0.56, respectively). Percutaneous
permeability of flurbiprofen-in-HPbetaCD-in-gels could be significantly
accelerated by turpentine oil and was related to the water content in the system.
An in vivo pharmacokinetic study showed a 2-fold increase in Cmax and a shortened
Tmax as well as a comparable relative bioavailability when compared with the
commercial flurbiprofen Cataplasms (Zepolas(r)). With their superior dissolution,
these flurbiprofen/HPbetaCD inclusion complexes prepared by SCF processing could
provide improved applications for flurbiprofen.
PMID- 28402144
TI - Expression and localization of Yap and Taz during development of the mandibular
first molar in rats.
AB - Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding
motif (Taz) are two downstream factors in the Hippo signaling pathway. Yap and
Taz participate in regulating organ size, stem cell self-renewal, proliferation
and differentiation. We investigated the spatial-temporal expression and relative
expression levels of Yap and Taz using immunohistochemistry and real-time
polymerase chain reaction. We found Yap and Taz in the oral epithelium and
mesenchyme at embryonic (E) day 14.5 (E14.5) and E16.5. By E18.5, Yap and Taz
were detected in the dental papilla and the entire enamel organ. At postnatal (P)
day 0 (PN0), PN3 and PN7, Yap and Taz expression was localized in ameloblasts,
odontoblasts and stratum intermedium. Yap and Taz were expressed in Hertwig's
epithelial root sheath (HERS) at PN7. At PN3, PN7 and PN14, Yap was detected in
the enamel matrix. From PN21 to PN28, Yap and Taz were absent from differentiated
ameloblasts, but they were expressed in odontoblasts. From PN0 to PN10, the Yap
and Taz mRNA expression increased, then decreased. We found that Yap and Taz may
influence the differentiation of ameloblasts and odontoblasts; they also may
contribute to enamel mineralization, crown morphogenesis and root formation.
PMID- 28402145
TI - The effect of pH, buffer capacity and ionic strength on quetiapine fumarate
release from matrix tablets prepared using two different polymeric blends.
AB - The objective of this study was to investigate the effect of the different
physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity,
and ionic strength) on the in vitro release of the weakly basic BCS class II drug
quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and
F2) developed as potential generic equivalents to Seroquel(r) XR. F1 tablets were
prepared using blends of high and low viscosity grades of hydroxypropyl
methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were
prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol(r) HD5 ATO).
The two formulations attained release profiles of QF over 24 h similar to that of
Seroquel(r) XR using the dissolution medium published by the Food and Drug
Administration (FDA). A series of solubility and in vitro dissolution studies was
then carried out using media that simulate the gastric and intestinal fluids and
cover the physiological pH, buffer capacity and ionic strength range of the GIT.
Solubility studies revealed that QF exhibits a typical weak base pH-dependent
solubility profile and that the solubility of QF increases with increasing the
buffer capacity and ionic strength of the media. The release profiles of QF from
F1, F2 and Seroquel(r) XR tablets were found to be influenced by the pH, buffer
capacity and ionic strength of the dissolution media to varying degrees. Results
highlight the importance of studying the physiological variables along the GIT in
designing controlled release formulations for more predictive in vitro-in vivo
correlations.
PMID- 28402146
TI - Long-term floating control-released intravesical preparation of 5-fluorouracil
for the local treatment of bladder cancer.
AB - In order to overcome the low compliance due to the frequent bladder perfusion of
anti-cancer drugs in the treatment of bladder cancer, a long-term control-release
of the anticancer drug in the bladder, the floating intravesical preparation was
developed. 5-fluorouracil was used as model drug. The floating preparations were
prepared by tableting (mini-tablets) and melting (mini-pellets) method. The
proportion of 5-fluorouracil and glyceryl tristearate (GTS) was altered among
formulations. Dissolution test, differential scanning calorimetry (DSC), X-ray
powder diffraction (XRPD) and scanning electron microscope (SEM) were used to
investigate the in vitro properties of the formulations. The in vivo evaluation
was carried out in beagle dogs. The control-release property of the preparation
was not only related to the content of 5-fluorouracil but also related to the
preparing method. The releasing time of the mini-tablets was nearly several days,
whereas that of the mini-pellets was almost several weeks. DSC and XRPD showed
that GTS had polymorphic conversion in the preparing process, therefore, the
stabilization procedure was necessary at the end of preparing. In vivo evaluation
showed that the prepared long-term floating preparations could maintain an
effective 5-fluorouracil concentration in the bladder for about one month,
furthermore, in this period the 5-fluorouracil concentration in blood was always
far less than that in urine.
PMID- 28402147
TI - Solubility and dissolution rate improvement of the inclusion complex of apigenin
with 2-hydroxypropyl-beta-cyclodextrin prepared using the liquid antisolvent
precipitation and solvent removal combination methods.
AB - Apigenin (AP) has many pharmacological activities. AP has poor solubility in some
solvents. AP is insoluble in water and slightly soluble in ethanol (1.93 mg/ml).
It has limited application and exploitation. Therefore, the liquid antisolvent
precipitation (LAP) method was applied to improve the solubility of AP in ethanol
by changing its crystal form or producing ultra-fine particles. Then, the
inclusion complex of AP with 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is
prepared using the solvent removal method. The effects of various experimental
parameters on the solubility of AP in ethanol were investigated through the
single factor design. Under the optimum conditions, the AP-ethanol solution of
6.19 mg/ml was obtained. The inclusion complex of AP with HP-beta-CD was obtained
by the solvent removal method. The load efficiency (LE) and drug encapsulation
efficiency (EE) of the inclusion complex of AP with HP-beta-CD were 13.98%+/
0.14% and 97.86%+/-1.07%, respectively. SEM, FTIR, 1HNMR, XRD, DSC and TG were
used to analyze the characteristics of the inclusion complex of AP with HP-beta
CD. These results showed that the inclusion complex has significantly different
characteristics with AP. In addition, the dissolution rate and solubility of the
inclusion complex were approximately 15.24 and 68.7 times higher than AP in
artificial gastric juice, and was separately 10.4 times and 40.05 times higher
than AP in artificial intestinal juice. The bioavailability of inclusion complex
increased 3.97 times compared with AP.
PMID- 28402148
TI - Should modulation of p50 be a therapeutic target in the critically ill?
AB - INTRODUCTION: A defining feature of human hemoglobin is its oxygen binding
affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50%
saturated (p50), and the variability of this parameter over a range of
physiological and environmental states. Modulation of this property of hemoglobin
can directly affect the degree of peripheral oxygen offloading and tissue
oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen
affinity in normal and abnormal physiology and discusses the current state of the
literature regarding artificial modulation of p50. Hypoxic tumors, sickle cell
disease, heart failure, and transfusion medicine are discussed in the context of
recent advances in hemoglobin oxygen affinity manipulation. Expert commentary: Of
particular clinical interest is the possibility of maintaining adequate end-organ
oxygen availability in patients with anemia or compromised cardiac function via
an increase in systemic p50. This increase in systemic p50 can be achieved with
small molecule drugs or a packed red blood cell unit processing variant called
rejuvenation, and human trials are needed to better understand the potential
clinical benefits to modulating p50.
PMID- 28402150
TI - Motivational and Parental Mediation Factors Related to Kenyan Adolescents' Intake
of Sexual Radio and TV Content.
AB - Research on the influence of media on youths' sexual behavior in sub-Saharan
Africa has focused almost entirely on the effects of multimedia health
communication campaigns and edutainment programming. Scholarly literature is
nearly silent about the influence of the multiple hours that young people in many
sub-Saharan nations spend immersed in increasingly sex-heavy entertainment
programming. We surveyed a stratified cluster sample of 437 Nairobi public high
school students about motivational and parental mediation factors associated with
their exposure to sexual radio and TV content. Watching sexual content in the
bedroom predicted higher intake of both sexual radio and TV content. Believing
that parents were successful in their efforts to limit media use predicted lower
intake of both sexual radio and TV content. A friend/companion motive for
watching was associated with taking in higher levels of sexual TV content. For
day school students, watching sexual content in the sitting room also predicted
higher levels of exposure to sexual TV content.
PMID- 28402149
TI - A new prenylated flavone from Pleione bulbocodioides.
AB - A new prenylated flavone, 3,5,7,3'-tetrahydroxy-8,4'-dimethoxy-6-(3-methylbut-2-
enyl)flavone (1), together with three known flavone derivatives (2-4), two known
dihydrophenanthrenes (5-6), two known lignin derivatives (7-8), and three known
phenolic glycoside compounds (9-11) were isolated from the n-BuOH extract of
Pleione bulbocodioides. High-resolution electrospray ionization mass spectroscopy
(HRESIMS), FTIR spectroscopy, and NMR techniques were used to elucidate the
structures of these compounds. Biological investigations showed that compound 5,
4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene, exhibited potent anti
inflammatory activity on LPS-stimulated NO production in BV-2 microglial cells,
with IC50 value of 5.44 MUM.
PMID- 28402151
TI - Tanshinone inhibits neuronal cell apoptosis and inflammatory response in cerebral
infarction rat model.
AB - We aimed to investigate the effect and mechanisms of tanshinone (TSN) IIA in
cerebral infarction. The cerebral infarction rat model was established by middle
cerebral artery occlusion (MCAO). After pretreatment with TSN, cerebral infarct
volume, cerebral edema, and neurological deficits score were evaluated, as well
as cell apoptosis in hippocampus and cortex of the brain was examined with
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the
levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C
reactive protein (CRP) were determined by Enzyme-Linked Immunosorbent Assay
(ELISA). In addition, rat primary neuronal cells were isolated and cultured in
oxygen-glucose deprivation (OGD) conditions. After pretreatment with TSN, cell
viability and apoptosis were observed by 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis,
respectively. The expressions of Bax and B-cell lymphoma 2 (Bcl-2) were detected
by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and
western blotting. Compared with untreated cerebral infarction rat, TSN treatment
significantly reduced cerebral infarct volume, cerebral edema, and neurological
deficits score ( P < 0.05). Cell apoptosis as well as the levels of IL-6, TNF
alpha, and CRP in hippocampus and cortex of cerebral infarction rat were
inhibited after pretreatment with TSN ( P < 0.05). Furthermore, TSN remarkably
increased cell viability and inhibited cell apoptosis ratio ( P < 0.05) in OGD
induced rat neuronal cells. Besides, TSN significantly downregulated the
expression of Bax and upregulated Bcl-2 ( P < 0.05). TSN IIA has a preventive
effect on cerebral infarction by inhibiting neuronal cell apoptosis and
inflammatory response in vitro and in vivo.
PMID- 28402152
TI - Daptomycin nonsusceptible vancomycin resistant Enterococcus bloodstream
infections in patients with hematological malignancies: risk factors and
outcomes.
AB - Daptomycin is typically the treatment of choice for vancomycin resistant
Enterococcus (VRE) bloodstream infections (BSI) in patients with hematological
malignancies, but increasingly daptomycin nonsusceptible VRE are being reported.
We reviewed our experience with daptomycin nonsusceptible VRE BSI among patients
with hematological malignancies. We compared risk factors and outcomes of 20
patients with daptomycin nonsusceptible VRE BSI (case patients) with 40 matched
control patients with daptomycin susceptible VRE BSI. Case patients had more
complications (6/20 vs. 2/40, p = .013); all-cause mortality was similar in both
groups. By multivariable analysis, only prior daptomycin exposure within 90 days
was significantly associated with daptomycin nonsusceptible VRE BSI (odds ratio
26.71; p < .0001). In 25% of case patients, all of whose VRE isolates had an
initial minimum inhibitory concentration (MIC) of 4 MUg/mL, nonsusceptibility
developed during treatment, raising the question of whether higher doses of
daptomycin should be used for VRE BSI in hematology patients.
PMID- 28402155
TI - Editors' Note.
PMID- 28402154
TI - Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease
in patients with acute myeloid leukemia.
AB - Invasive fungal diseases (IFD) are still a leading cause of morbidity and
mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate
dehydrogenase is an enzyme that leads to the production of NADPH, required to
destroy microorganisms in the respiratory burst reaction of white blood cells. We
evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML
patients undergoing intensive chemotherapy. In all, 28 patients harbored G6PD
deficiency (G6PD-), whereas 80 were normal (G6PD +). Incidence of IFD was
significantly higher in G6PD- patients compared to G6PD + patients (35.7% vs. 5%,
p = .0002, OR = 10, 95% CI = 2.96-37.5). Higher risk of mold infections (17.9%
vs. 5%, p = .048, OR = 4.1, 95% CI = 1.0-16.6) and Candida sepsis (17.9% vs. 0%,
p = .0009, OR = 37.68, 95% CI =2.0-707.1) was observed in G6PD - patients. The
evaluation of G6PD activity may help to identify AML patients at higher risk of
IFD, allowing to design more intensive surveillance and therapeutic strategies.
PMID- 28402153
TI - Maternal-Fetal Transmission of Zika Virus: Routes and Signals for Infection.
AB - The emerging mosquito-borne virus, Zika virus (ZIKV), has been causally
associated with adverse pregnancy and neonatal outcomes, including miscarriage,
microcephaly, serious brain abnormalities, and other birth defects indicative of
a congenital ZIKV syndrome. In this review, we highlight work from human and
animal studies on routes of infection in pregnancy that lead to adverse fetal and
neonatal outcomes. A number of innate and adaptive immune mechanisms and
signaling molecules that may have key roles in ZIKV infection pathogenesis are
discussed along with putative viral entry pathways. A more granular understanding
of pathogenesis of ZIKV infection during pregnancy is critical for developing
therapeutics and vaccines and mounting a global public health response to limit
ZIKV infections. We also report on new therapeutic interventions that have shown
success in preclinical studies.
PMID- 28402156
TI - Efficacy and Safety of Patiromer in Hyperkalemia: A Systematic Review and Meta
Analysis.
AB - BACKGROUND: Patients at the highest risk of hyperkalemia are those with chronic
kidney disease (CKD) stages 3 and 4. OBJECTIVE: To evaluate the efficacy and
safety of patiromer in hyperkalemia in patients with heart failure or CKD.
METHODS: The Cochrane Renal Group's Specialized Register was searched through
contact with the Trials' Search Coordinator. We aimed at including randomized
controlled trials with patiromer in patients with developed or risks of
developing hyperkalemia, comparing against an active comparator or placebo. Three
studies matched our inclusion and exclusion criteria, which we included in the
meta-analysis. All-cause mortality, reduction in hospitalization, episodes of
hypokalemia or hyperkalemia, and cardiovascular and gastrointestinal adverse
events during the treatment period were our primary outcomes. Serial change in
serum potassium (K+) until end of treatment or follow-up during the trial period
and all other reported adverse reactions during the treatment period were our
secondary outcomes. Meta-analysis (RevMan version 5.3.5) and descriptive
statistics were used. RESULTS: There was a non-significant improvement in all
cause mortality and serious cardiovascular events with patiromer than placebo.
Hospitalization data were unavailable. Although serious gastrointestinal events
were more common with placebo, there was a significant reduction ( P = .02) in
the risk of non-serious gastrointestinal events with placebo. Patiromer lowered
serum K+ more than placebo, and there were more patients developing hyperkalemia
with placebo. High-dose patiromer was associated with better efficacy in some
parameters but with more adverse events. CONCLUSION: Although patiromer seems
promising, more trials with active comparator are essential to finalize its
indication and use in hyperkalemia.
PMID- 28402157
TI - Tradeoff between resistance induced by volatile communication and over-topping
vertical growth.
AB - Plants commonly respond to reliable cues about herbivores by inducing greater
defenses. Defenses are assumed to incur costs for plants when they are not
needed. Sagebrush responds to volatile cues from experimentally clipped neighbors
to induce resistance against chewing herbivores. Rather than experiencing costs,
sagebrush seedlings that responded to dishonest cues were previously found to
have increased survival and established plants that responded produced more
inflorescences and new lateral branches. Here I report that young sagebrush
plants that responded to cues added less vertical growth than controls that were
not presented with volatile cues. This tradeoff between induced resistance and
vertical, overtopping growth may allow agronomists to increase defense without
sacrificing desirable traits. Overtopping growth is often beneficial for wild
plants but often detrimental in agriculture.
PMID- 28402158
TI - Is integrated information management a core clinical skill required for the
doctor-patient encounter?
PMID- 28402159
TI - Population healthcare: designing population-based systems.
PMID- 28402160
TI - Ureteroscopy-Assisted Laparoscopic Segmental Resection of Ureteral Stricture with
a Modified Flank Position: Clinical Experience.
AB - PURPOSE: To share the surgical technique that possesses the advantage of a
perioperative ureteroscope without position change, which allows for a
laparoscopic segmental resection of the ureteral stricture to be performed more
precisely. PATIENTS AND METHODS: Between 2006 January and 2015 December, 10
patients with a ureteral stricture received a laparoscopic segmental resection
and ureteroureterostomy in our clinical institute. The etiology included stone,
endometriosis, crossing vessel, and idiopathic benign ureteral polyp. With the
advance of bilateral lower extremities extended and abducted, 1 assistant used a
ureteroscope as a direct guide to the precise location of the stricture affected
ureter. Thus, the surgeon was able to perform a more specific resection without
an unnecessary excision, which may have compromised the blood supply or increased
the tension at anastomosis. RESULTS: Five patients received the traditional
transperitoneal laparoscopic approach, whereas the other 5 patients received a
ureteroscopy-assisted laparoscopic segmental resection and ureteroureterostomy.
The operating time appears to be no different between the two groups (124 minutes
versus 142 minutes, P = .351), and, thus, no additional time is consumed for the
ureteroscope procedure. After at least 1 year of follow-up, only 1 patient in the
traditional laparoscopic group suffered from recurrence. One patient had a right
ureteral stricture due to stone impaction, where with the advantage of a
ureteroscope guide without change position, the operator was able to make a
limited excision at the affected location. No complications related to the
decubitus and bilateral leg in the extended position were noted. CONCLUSIONS:
Ureteroscopy-assisted laparoscopic segmental resection of the ureter without a
change in position is a feasible and safe procedure when dealing with a
refractory ureter stricture. Although it is convenient, the surgeon should be
aware of possible pressure sores at the dependent part.
PMID- 28402161
TI - EIN2-mediated signaling is involved in pre-invasion defense in Nicotiana
benthamiana against potato late blight pathogen, Phytophthora infestans.
AB - Nicotiana benthamiana ABCG1 and ABCG2 are ABC transporters which are probably
involved in the export of capsidiol, the major phytoalexin of Nicotiana species.
While capsidiol export by these transporters plays an essential role in post
invasion defense against Phytophthora infestans, they also export unidentified
antimicrobial compound(s) involved in pre-invasion defense. In this study,
promoter activity of NbABCG2 (Pabcg2a) was analyzed using a GFP marker.
Expression of GFP under the control of Pabcg2a was significantly increased by co
expression with the INF1 elicitor from P. infestans. Disruption of the ethylene
responsive GCC box in Pabcg2a compromised INF1-induced activation of Pabcg2a.
Consistently, penetration by P. infestans was increased by gene-silencing of
NbEIN2, the key ethylene-signaling component, suggesting the involvement of
ethylene for pre-invasion defense of N. benthamiana.
PMID- 28402162
TI - Barriers preventing the adoption of comprehensive cancer genomic profiling in the
clinic.
AB - INTRODUCTION: Comprehensive cancer genomic profiling provides the opportunity to
expose the various molecular aberrations potentially driving tumor progression.
Consequently, the identity of these genetic drivers can be utilized to match a
patient to the most appropriate targeted therapy, thereby increasing the
probability of improved clinical outcome. Despite its capability of informing
patient care, the adoption of comprehensive cancer genomic profiling in the
clinic has not been widespread. The barriers surrounding its universal acceptance
are attributed to both physician and patient perspectives. Areas covered: The
following report discusses the various obstacles in place, including those
related to clinical utility, education, insurance coverage, and clinical trials,
which can deter physicians and patients from utilizing genomic profiling for
therapeutic decision-making. Expert commentary: The authors review the recent
growth and potential of clinical utility studies over the last two years, provide
a suggestive framework for educational support, and comment on the use of social
media to enhance clinical trial recruitment.
PMID- 28402163
TI - Bortezomib, melphalan, and prednisone in elderly relapsed/refractory multiple
myeloma patients: update of multicenter, open-label Phase 1/2 study.
PMID- 28402164
TI - HiJAKing the epigenome in leukemia and lymphoma.
AB - The Janus kinase (JAK)/signal transducer and activator of transcription (STAT)
pathway is central to signaling by receptors of diverse cytokines, growth
factors, and other related molecules. Many of these receptors transmit anti
apoptosis, proliferation, and differentiation signals that are critical for
normal hematopoiesis and immune response. However, the JAK/STAT signaling pathway
is deregulated in many hematologic malignancies, and as such is co-opted by
malignant cells to promote their survival and proliferation. It has recently come
to light that an alternative mechanism, wherein nuclear JAKs epigenetically
modify the chromatin to increase gene expression independent of STATs, also plays
an important role in the pathogenesis of many hematologic malignancies. In this
review, we will focus on common genetic alterations of the JAK family members in
leukemia and lymphoma, and provide examples in which JAKs regulate gene
expression by targeting the cancer epigenome.
PMID- 28402165
TI - Statistical properties of continuous composite scales and implications for drug
development.
AB - Little research has been conducted on the statistical properties of composite
measures comprising linear combinations of continuous component scales. We
assessed the quantitative relationship between the composites and their
individual components regarding their abilities to detect treatment effects. In
particular, we developed the mathematical derivation of the treatment effect size
of a continuous composite in relation to the treatment effect sizes of its
components and proved multiple properties of the composite. We demonstrated that
the treatment effect size of a composite is greater than the minimum treatment
effect size of its components and that above certain thresholds of correlations
of components and ratios of component effect sizes, the composite may outperform
its components. Examples from Alzheimer's disease (AD) clinical studies of
solanezumab and donepezil using the composite Integrated AD Rating Scale (iADRS)
and its components, the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and AD
Cooperative Study-Activities of Daily Living inventory, instrumental items (ADCS
iADL) were consistent with the theoretical statistical properties. The
understanding of the quantitative relationships between continuous composites and
their components will be useful in clinical trial design and the development of
new scales and composites across therapeutic areas.
PMID- 28402167
TI - Multiinstitutional Analysis of Thyroid Nodule Risk Stratification Using the
American College of Radiology Thyroid Imaging Reporting and Data System.
AB - OBJECTIVE: Guidelines for managing thyroid nodules are highly dependent on risk
stratification based on sonographic findings. The purpose of this study is to
evaluate the risk stratification system used by the American College of Radiology
Thyroid Imaging Reporting and Data System (TIRADS). MATERIALS AND METHODS:
Patients with thyroid nodules who underwent sonography and fine-needle aspiration
were enrolled in a multiinstitutional study. The sonographic nodule features
evaluated in the study were composition, echogenicity, margins, and echogenic
foci. Images were reviewed by two radiologists who were blinded to the results of
cytologic analysis. Nodules were assigned points for each feature, and the points
were totaled to determine the final TIRADS level (TR1-TR5). The risk of cancer
associated with each point total and final TIRADS level was determined. RESULTS:
A total of 3422 nodules, 352 of which were malignant, were studied. The risk of
malignancy was closely associated with the composition, echogenicity, margins,
and echogenic foci of the nodules (p < 0.0001, in all cases). An increased
aggregate risk of nodule malignancy was noted as the TIRADS point level increased
from 0 to 10 (p < 0.0001) and as the final TIRADS level increased from TR1 to TR5
(p < 0.0001). Of the 3422 nodules, 2948 (86.1%) had risk levels that were within
1% of the TIRADS risk thresholds. Of the 474 nodules that were more than 1%
outside these thresholds, 88.0% (417/474) had a risk level that was below the
TIRADS threshold. CONCLUSION: The aggregate risk of malignancy for nodules
associated with each individual TIRADS point level (0-10) and each final TIRADS
level (TR1-TR5) falls within the TIRADS risk stratification thresholds. A total
of 85% of all nodules were within 1% of the specified TIRADS risk thresholds.
PMID- 28402168
TI - Performance Evaluation of Automated Impedance and Optical Fluorescence Platelet
Counts Compared With International Reference Method in Patients With Thalassemia.
AB - CONTEXT: - Spurious platelet counts from automated methods have been reported in
patients with abnormal red blood cells. However, there is no specific study
regarding performance of platelet counts by automated methods in patients with
thalassemia. OBJECTIVE: - To investigate the performance of automated platelet
counts, including impedance (PLT-I) and optical fluorescent (PLT-O and PLT-F)
methods, and compare them with the international reference method (IRM) for
platelet counting in patients with thalassemia. DESIGN: - Two hundred forty-nine
thalassemia specimens from various subtypes were examined. PLT-I, PLT-O, and PLT
F from a Sysmex XN analyzer were evaluated and compared against the IRM.
Demographic data, platelet counts, and red blood cell parameters are shown.
Comparability between evaluated methods and IRM, as well as test characteristics,
is presented. Factors involving inaccurate PLT-I were analyzed. RESULTS: -
Specimens with platelet counts ranging from 31 * 103/MUL to 932 * 103/MUL were
included. Most patients were patients with thalassemia major. Correlation between
PLT-I and IRM was lower than that of the other methods in overall patients. PLT-O
and PLT-F were correlated to IRM when classifying patients according to
clinically significant platelet ranges. All automated methods had acceptable
sensitivities; however, specificity of PLT-I was low for diagnosis of
thrombocytopenia. High RDW-CV (red blood cell distribution width-coefficient of
variation) was an independent factor of inaccurate PLT-I measurement.
CONCLUSIONS: - Among the evaluated methods, PLT-I was the method least correlated
to IRM, with PLT-O and PLT-F comparable to IRM in patients with thalassemia.
Optical platelet counts and careful blood smear examination are recommended
alternative platelet counting methods, depending on the clinical setting.
PMID- 28402169
TI - Delta Check Practices and Outcomes: A Q-Probes Study Involving 49 Health Care
Facilities and 6541 Delta Check Alerts.
AB - CONTEXT: - Delta checks serve as a patient-based quality control tool to detect
testing problems. OBJECTIVE: - To evaluate delta check practices and outcomes.
DESIGN: - Q-Probes participants provided information about delta check policies
and procedures. Information about investigations, problems, and corrective
actions was prospectively collected for up to 100 testing episodes involving
delta check alerts. RESULTS: - Among 4505 testing episodes involving 6541 delta
check alerts, the median frequencies of actions taken among 49 laboratories were
clinical review, 38.0%; retest, 25.0%, or recheck, 20.2%; current specimen,
nothing, 15.4%; analytical check, 5.0%; other; 2%; and retest or check previous
specimen, 0%. Rates of any action taken by analyte ranged from 84 of 179 (46.9%)
for glucose to 748 of 868 (86.2%) for hemoglobin and potassium. Among 4505
testing episodes, nontesting problems included physiologic causes (1472; 32.7%);
treatment causes (1318; 19.2%); and transfusion causes (846; 9.9%). Testing
problems included 77 interference (1.7%), 62 contamination (1.4%), 51 clotting
(1.1%), 27 other (0.6%), 12 mislabeling (0.3%), and 5 analytical (0.1%). Testing
problems by analyte ranged from 13 of 457 (2.8%) for blood urea nitrogen to 12 of
46 (26.1%) for mean corpuscular hemoglobin concentration. Using more delta check
analytes was associated with detecting more testing problems (P = .04). More
delta check alerts per testing episode resulted in more actions taken (P = .001)
and more problems identified (P < .001). The most common outcome among 4500
testing episodes was reporting results without modifications or comments in 2512
(55.8%); results were not reported in 136 (3.0%). CONCLUSIONS: - Actions taken in
response to delta check alerts varied widely, and most testing problems detected
were preanalytical. Using a higher number of different analytes and evaluating
previous specimens may improve delta check practices.
PMID- 28402166
TI - Nrf2 promotes progression of non-small cell lung cancer through activating
autophagy.
AB - The transcription factor, NFE2-related factor 2 (Nrf2) and autophagy have been
implicated in the oxidative-stress response during tumor evolution. However, few
studies focus on crosstalk between Nrf2 and autophagy in cancer progression of
non-small cell lung cancer (NSCLC). Herein, we evaluated the effect of Nrf2 on
autophagy in NSCLC and their role in development of NSCLC. Effect of Nrf2 on
overal survival (OS) of NSCLC patients were evaluated. Cell biological behaviors
in response to Nrf2 were evaluated by MTT, colony formation assay and flow
cytometry. Effect of 3-MA (a classical inhibitor of autophagy) on 95D-Nrf2 cells
was also analyzed using flow cytometry. After up/down-regulating Nrf2 in NSCLC
cell lines, expression of autophagy-related proteins were evaluated with western
blot analysis. The results revealed that Nrf2 was an independent prognositc
factor negtively associated with OS of NSCLC patients. Elevated Nrf2 expression
promotes NSCLC progression, enhancing the escape of tumor cells from apoptosis in
vivo and in vitro. Double staining with Annexin V-APC and 7-AAD showed that the
proportions of apoptotic cells in 95D-Nrf2 cells were gradually increased after
the addition of 3-MA. Importently, Nrf2 induced autophagosome formation and
enhanced autophagic activity, which subsequently inhibits NSCLC cell apoptosis.
In conclusion, our present study demonstrates that Nrf2 promotes progression of
non-small cell lung cancer through activating autophagy. It provides novel
insights into Nrf2-mediated of cell proliferation in NSCLC and may facilitate
therapeutic development against NSCLC.
PMID- 28402170
TI - Control of the cost of medicines and medical supplies to the NHS: Health Service
and Medical Supplies (Costs) Act 2017.
PMID- 28402171
TI - Tethered bone morphogenetic protein-2 onto sulfonated-polyrotaxane based surfaces
promotes osteogenic differentiation of MC3T3-E1 cells.
AB - Sulfonated-polyrotaxane (PRX)-coated surfaces with tethered bone morphogenetic
protein-2 (BMP-2) were designed for inducing osteogenic differentiation of MC3T3
E1 cells (preosteoblasts). Sulfonated-PRX triblock copolymers composed of
sulfopropyl ether-modified alpha-cyclodextrins (alpha-CDs) threaded onto a
poly(ethylene glycol) (PEG) chain as a PRX segment and poly(benzyl methacrylate)
(PBzMA) at both terminals of the PEG as anchoring segments were synthesized by
reversible addition-fragmentation chain transfer (RAFT) polymerization. BMP-2
tethering on the PRX surfaces with a large number of threaded alpha-CDs was
suitable for the proliferation of MC3T3-E1 cells, regardless of the presence or
absence of sulfopropyl groups. However, the differentiation of MC3T3-E1 cells
according to mineralization assays and the gene expression levels of runt-related
transcription factor 2, alkaline phosphatase, and osteocalcin was markedly
enhanced by BMP-2 tethering on the sulfonated-PRX surface. These results suggest
that sulfonated-PRX surfaces can effectively promote the proliferation and induce
the osteogenic differentiation of MC3T3-E1 cells by the number of threaded alpha
CDs and tethered-BMP-2 using electrostatic interactions with sulfopropyl groups.
PMID- 28402172
TI - Rational design and synthesis of affinity matrices based on proteases immobilized
onto cellulose membranes.
AB - Discovery of new protease inhibitors may result in potential therapeutic agents
or useful biotechnological tools. Obtainment of these molecules from natural
sources requires simple, economic, and highly efficient purification protocols.
The aim of this work was the obtainment of affinity matrices by the covalent
immobilization of dipeptidyl peptidase IV (DPP-IV) and papain onto cellulose
membranes, previously activated with formyl (FCM) or glyoxyl groups (GCM). GCM
showed the highest activation grade (10.2 umol aldehyde/cm2). We implemented our
strategy for the rational design of immobilized derivatives (RDID) to optimize
the immobilization. pH 9.0 was the optimum for the immobilization through the
terminal alpha-NH2, configuration predicted as catalytically competent. However,
our data suggest that protein immobilization may occur via clusters of few
reactive groups. DPP-IV-GCM showed the highest maximal immobilized protein load
(2.1 ug/cm2), immobilization percentage (91%), and probability of multipoint
covalent attachment. The four enzyme-support systems were able to bind at least
80% of the reversible competitive inhibitors bacitracin/cystatin, compared with
the available active sites in the immobilized derivatives. Our results show the
potentialities of the synthesized matrices for affinity purification of protease
inhibitors and confirm the robustness of the RDID strategy to optimize protein
immobilization processes with further practical applications.
PMID- 28402174
TI - Paul of Aegina (ca 625-690 ad), Reconstructing Male Gynecomastia.
AB - Paul of Aegina thrived with his innovative operations, practically creating a
kind of a new surgical school. He had deeply believed in human's body perfection
introducing a series of cosmetic operations. Among them stood the male's breasts
reconstruction in the case of pseudo-gynecomastia. His intervention was
replicated by both the western Europeans and the Arabs.
PMID- 28402173
TI - Atherogenic Indices Are Increased in Elderly Patients with Unipolar Depression
Case-Control Analysis.
AB - BACKGROUND: Blood lipids are widely used in monitoring the risk of cardiovascular
diseases; however, atherogenic indices are more precise markers. The aim of the
study was to determine differences in atherogenic indices in elderly patients
with unipolar depression (DEP) compared with nondepressed elderly patients
(nonDEP) using case-control analysis. METHODS: Fasting serum lipid profiles were
measured in 564 (depressed: n = 282, nondepressed: n = 282, 83.7% (n = 236) women
in both groups) Caucasian inpatients aged >=60, with mean age 76.9 years.
Patients from both groups were matched for age and sex. Atherogenic index of
plasma (AIP) was calculated as log10(triglycerides/HDL cholesterol). Castelli
atherogenic indices were calculated as follows: AILDL/HDL is the ratio of low
density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL)
cholesterol and AITC/HDL is the ratio of total cholesterol to HDL cholesterol.
RESULTS: HDL levels were significantly decreased in depressed patients (48.2 +/-
14.4 mg/dL vs. 54.5 +/- 17.7 mg/dL). No other differences in lipid profile were
found. We found that all three analyzed atherogenic indices were increased in
depressed patients (AIP: 0.41 +/- 0.28 vs. 0.33 +/- 0.27, AILDL/HDL: 2.90 +/-
1.41 vs. 2.42 +/- 1.07, AITC/HDL: 4.51 +/- 1.84 vs. 3.79 +/- 1.21). We found
associations between depression severity and reduced level of HDL (beta = -0.02)
or increased AIP (beta = 1.66). CONCLUSIONS: All three atherogenic indices were
increased in elderly patients with depression. Since depression and age are
associated with elevated risk of cardiovascular events, elderly patients with
depression should be carefully monitored for abnormal lipid status to reduce
their cardiovascular risk. The role of lipid abnormalities in the pathogenesis of
depression requires further studies.
PMID- 28402176
TI - Identification of bacterial contaminants from calcium carbonate filler production
lines and an evaluation of biocide based decontamination procedures.
AB - The aim of this study was to analyze the bacterial community in the production
line of a calcium carbonate filler production company and to investigate possible
causes for bacterial presence. Throughout 2012, 24 carbonate slurry and six
groundwater samples were analyzed. Pseudomonas and Microbacterium were the most
frequent contaminants in the slurry, whereas Pseudomonas and Brevundimonas
dominated the groundwater samples. Of the 43 different bacterial strains
isolated, only five were found both in the slurry and the groundwater, indicating
that the latter was not a major source of contamination. The efficacy of 54
commercial biocidal formulations was tested against an artificial bacterial
consortium composed of selected slurry isolates. A formulation containing 7.5-15%
(v v-1) bronopol and 1.0-2.5% (v v-1) [chloroisothiazolinone (CIT) +
methylisothiazolinone (MIT)] exhibited the highest efficacy. Of the possible
causes for bacterial presence, sporogenesis and biocide adsorption to carbonate
particles were found to be less probable compared to bacterial adsorption to
particles, and the acquisition of resistance to biocides.
PMID- 28402175
TI - Development of drug-loaded chitosan hollow nanoparticles for delivery of
paclitaxel to human lung cancer A549 cells.
AB - In this study, biodegradable chitosan hollow nanospheres (CHN) were fabricated
using polystyrene nanospheres (PS) as templates. CHN were applied to increase the
solubility of poorly water-soluble drugs. The lung cancer drug paclitaxel (PTX),
which is used as a model drug, was loaded into CHN by the adsorption equilibrium
method. The drug-loaded sample (PTX-CHN) offered sustained PTX release and good
bioavailability. The state characterization of PTX by differential scanning
calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared
spectroscopy (FTIR) showed that the PTX absorbed into CHN existed in an amorphous
state. An in vitro toxicity experiment indicated that CHN were nontoxic as
carriers of poorly water-soluble drugs. The PTX-CHN produced a marked inhibition
of lung cancer A549 cells proliferation and encouraged apoptosis. A cell uptake
experiment indicated that PTX-CHN was successfully taken up by lung cancer A549
cells. Furthermore, a degradation experiment revealed that CHN were readily
biodegradable. These findings state clearly that CHN can be regarded as promising
biomaterials for lung cancer treatment.
PMID- 28402177
TI - Intersectional harassment and deviant embodiment among Autistic adults:
(dis)ability, gender and sexuality.
AB - Harassment scholarship increasingly attends to the intersectional nature of
harassment and its function within systems of domination. However, little of this
work includes disability. In-depth interviews with 24 adults on the autism
spectrum in the USA demonstrate the intersections of gender, sexuality and
(dis)ability in the construction of deviant embodiments as targets for
harassment. These intersections also shape how participants made sense of these
experiences of violence. Participants' disability characteristics were often read
as gender or sexual variance, with harassers relying on sexist and heterosexist
constructs to frighten, demean or humiliate them for disability characteristics.
Participant experiences demonstrate the cisgender basis of 'able-bodied' identity
as well as the 'able-bodied' basis of cisgender and heterosexual identities and
experiences. The interdependency of gender, sexuality and (dis)ability embodiment
point to how it is critical for scholars and activists to account for the role of
gender and heterosexist harassment in ableist oppression and disability
harassment in (hetero)sexist oppression, as well as the limits of current US law
enforcement structures in providing redress for harassment.
PMID- 28402178
TI - Top 10 Research Questions Related to Youth Aerobic Fitness.
AB - Peak oxygen uptake ([Formula: see text]2) is internationally recognized as the
criterion measure of youth aerobic fitness, but despite pediatric data being
available for almost 80 years, its measurement and interpretation in relation to
growth, maturation, and health remain controversial. The trainability of youth
aerobic fitness continues to be hotly debated, and causal mechanisms of training
induced changes and their modulation by chronological age, biological maturation,
and sex are still to be resolved. The daily physical activity of youth is
characterized by intermittent bouts and rapid changes in intensity, but physical
activity of the intensity and duration required to determine peak [Formula: see
text]2 is rarely (if ever) experienced by most youth. In this context, it may
therefore be the transient kinetics of pulmonary [Formula: see text]2 that best
reflect youth aerobic fitness. There are remarkably few rigorous studies of youth
pulmonary [Formula: see text]2 kinetics at the onset of exercise in different
intensity domains, and the influence of chronological age, biological maturation,
and sex during step changes in exercise intensity are not confidently documented.
Understanding the trainability of the parameters of youth pulmonary [Formula: see
text]2 kinetics is primarily based on a few comparative studies of athletes and
nonathletes. The underlying mechanisms of changes due to training require further
exploration. The aims of the present article are therefore to provide a brief
overview of aerobic fitness during growth and maturation, increase awareness of
current controversies in its assessment and interpretation, identify gaps in
knowledge, raise 10 relevant research questions, and indicate potential areas for
future research.
PMID- 28402179
TI - Antiviral Effect of IDO in Mouse Fibroblast Cells During Influenza Virus
Infection.
AB - While upregulation of 2,3-dioxygenase (IDO) accompanied by degradation of
tryptophan along the kynurenine pathway have been reported to exert antimicrobial
effects against a wide range of infectious agents, its role in the replication of
influenza A virus remains uncertain. We performed experiments using influenza
A/WSN/33 virus infection of mouse fibroblast cell-line (NIH-3T3) to study the
effects of IDO on viral replication. Influenza infection resulted in prominent
elevations of transcripts encoding IDO, interferon (IFN)-beta, and segment 8 of
the virus in NIH-3T3 cells. Introduction of siRNA targeted against IDO followed
by infection resulted in further increased levels of viral RNA without altering
IFN-beta expression. Inhibition of IDO during the infection also resulted in
reduction of virus-driven upregulation of 3-hydroxyanthranilate 3,4-dioxygenase
(HAAO), but not kynurenine 3-monooxygenase (KMO), which are enzymes downstream in
the kynurenine pathway. Thus, induction of IDO appears to contribute to limiting
replication of the WSN/33 strain of influenza A virus in murine NIH-3T3 cells.
PMID- 28402180
TI - Analytical determination of bisphenol A (BPA) and bisphenol analogues in paper
products by GC-MS/MS.
AB - Bisphenol A (BPA; 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol), a suspected
endocrine disruptor with a weak estrogenic activity, is used in a variety of
consumer products, including food-contact materials made of paper and cardboard
products. Due to restrictions on the use of BPA because of its potential health
risks, BPA is gradually being replaced by other bisphenols because no limitations
exist for these substances. This study presents a method for the simultaneous
analysis of BPA, bisphenol AF (BPAF), bisphenol B (BPB), bisphenol E (BPE),
bisphenol F (BPF) and bisphenol S (BPS) in paper and board products using gas
chromatography-tandem mass spectrometry (GC-MS/MS). Paper samples were extracted
by liquid extraction, as well as by Folch extraction, derivatised with N,O
bis(trimethylsilyl)trifluoroacetamide (BSTFA) and the results compared. The
developed method showed good linearity (R2 > 0.9965) and precision, yielding
relative standard deviations (RSDs) of less than 16.6% for reproducibility and
19.8% for repeatability. The limits of detection and limits of quantification for
the different bisphenols ranged from 0.23 to 2.70 ug kg-1 paper and from 0.78 to
9.10 ug kg-1 paper, respectively. Analysis of different paper products (recycled,
virgin fibre) showed that all the analysed bisphenols were present in the
samples, except for BPAF and BPB. A calculation of the 'worst-case' scenario
assuming a maximum potential migration of 100% of the analytes into food showed
that the analysed products can be assumed to be safe regarding the migration of
bisphenols.
PMID- 28402181
TI - Chemical composition of rosehips from different Rosa species: an alternative
source of antioxidants for the food industry.
AB - It is important to explore new sources of natural additives because the demand
for these compounds by consumers is increasing. These products also provide
health benefits and help in food preservation. An unexplored source of nutrients
and antioxidant compounds is rosehip, the fleshy fruit of roses. This work
compares the antioxidant compound (vitamin C, neutral phenols and acidic phenols)
content of four Rosa species rosehips: R. pouzinii, R. corymbifera, R. glauca and
R. canina from different geographical zones. Results show quantitative
variability in ascorbic acids and neutral phenols content, and quantitative and
qualitative differences in acidic phenol content, depending on species. Vitamin C
concentration was highly variable depending on species, R. canina being the one
with the highest concentration and R. pouzinii the one with the lowest content.
Variability was found in total neutral polyphenols concentration and a
correlation between freshness of the rosehips and concentration of neutral
polyphenols was also found. Significant differences were found in the acidic
phenols content among the studied species. Generally antioxidant activity was
higher in the vitamin C fraction.
PMID- 28402182
TI - Analysis of Point Mutations in the pbp2x, pbp2b, and pbp1a Genes of Streptococcus
agalactiae and Their Relation with a Reduced Susceptibility to Cephalosporins.
AB - The emergence of group B Streptococcus (GBS) isolates with reduced penicillin
susceptibility (PRGBS) and their tendency to be nonsusceptible to
fluoroquinolones prompted us to analyze the possible presence of amino acid
mutations in penicillin-binding proteins (PBPs) (PBP2X, PBP1A, and PBP2B) from a
collection of fluoroquinolone-resistant GBS isolates. We analyzed 21 GBS isolates
resistant to levofloxacin. Sequence analysis of genes for PBPs was performed. The
minimal inhibitory concentrations (MICs) for penicillin, ceftibuten, cefaclor,
cefixime, cefotaxime, and ceftizoxime were performed by the Etest method and by
broth microdilution method. The isolates were furthermore characterized by PCR
based capsular typing and analysis of surface protein genes. Genetic relatedness
among the isolates was examined by multilocus sequence typing. Phylogenetic
analysis of PBPs sequences was performed by Molecular Evolutionary Genetics
Analysis software (MEGA7). All isolates were susceptible to penicillin, even if
different mutations were detected in all PBPs in most of the isolates (12/21,
57%). However, we observed a reduced susceptibility to cefixime in seven isolates
and to cefaclor in six isolates. These PSGBS isolates shared an I377V mutation in
PBP2X and a T145A mutation in PBP1A. Most of the isolates belongs to the clonal
complex 1, has serotype III and rib as surface protein. The results of
phylogenetic comparative analysis show that several genetic lineages of our
isolates with reduced susceptibility to cefixime/cefaclor have been independently
emerging through the accumulation of mutations in their pbp genes, especially in
pbp1a. If the MICs of penicillins and cephalosporins for GBS increase, careful
epidemiological surveillance on this issue is recommended.
PMID- 28402183
TI - Halloween Costume Choices: Reflections of Gender Development in Early Childhood.
AB - The author examined whether preschoolers' Halloween costume choices reflect their
gender development. The sample consisted of 110 (53 boys, 57 girls) infant
through preschool-aged participants, and 1 parent of each child. Both
observational methodologies and parent-report surveys were used to assess the
gender-typed nature of children's Halloween costumes, information about the
Halloween costume choice process, and about the children's gender development.
Boys' costumes were more masculine and girls' costumes were more feminine.
Younger children's costumes were consistently less gender typed than the older
children's costumes were. Children whose parents chose their Halloween costumes
for them had Halloween costumes that were less gender typed than did children who
were involved in the Halloween costume decision-making process. Moreover,
children's gender-typed play and desire to wear gender-stereotyped clothes were
related to the gender stereotyped nature of their Halloween costume.
Unexpectedly, gender typicality, a dimension of gender identity, was not related
to children's Halloween costume choices. Overall, the findings support that
children's Halloween costume choice is an indicator of children's gender
development processes.
PMID- 28402184
TI - Root-Knot Nematode Parasitism Suppresses Host RNA Silencing.
AB - Root-knot nematodes damage crops around the world by developing complex feeding
sites from normal root cells of their hosts. The ability to initiate and maintain
this feeding site (composed of individual "giant cells") is essential to their
parasitism process. RNA silencing pathways in plants serve a diverse set of
functions, from directing growth and development to defending against invading
pathogens. Influencing a host's RNA silencing pathways as a pathogenicity
strategy has been well-documented for viral plant pathogens, but recently, it has
become clear that silencing pathways also play an important role in other plant
pathosystems. To determine if RNA silencing pathways play a role in nematode
parasitism, we tested the susceptibility of plants that express a viral
suppressor of RNA silencing. We observed an increase in susceptibility to
nematode parasitism in plants expressing viral suppressors of RNA silencing.
Results from studies utilizing a silenced reporter gene suggest that active
suppression of RNA silencing pathways may be occurring during nematode
parasitism. With these studies, we provide further evidence to the growing body
of plant-biotic interaction research that suppression of RNA silencing is
important in the successful interaction between a plant-parasitic animal and its
host.
PMID- 28402185
TI - Giardiasis Outbreak Associated with Asymptomatic Food Handlers in New York State,
2015.
AB - Giardia duodenalis is a protozoan that causes a gastrointestinal illness called
giardiasis. Giardiasis outbreaks in the United States are most commonly
associated with waterborne transmission and are less commonly associated with
food, person-to-person, and zoonotic transmission. During June to September 2015,
an outbreak of 20 giardiasis cases occurred and were epidemiologically linked to
a local grocery store chain on Long Island, New York. Further investigation
revealed three asymptomatic food handlers were infected with G. duodenalis , and
one food handler and one case were coinfected with Cryptosporidium spp. Although
G. duodenalis was not detected in food samples, Cryptosporidium was identified in
samples of spinach dip and potato salad. The G. duodenalis assemblage and subtype
from one of the food handlers matched two outbreak cases for which genotyping
could be performed. This outbreak highlights the potential role of
asymptomatically infected food handlers in giardiasis outbreaks.
PMID- 28402186
TI - Inhibition of Hafnia alvei H4 Biofilm Formation by the Food Additive
Dihydrocoumarin.
AB - Quorum sensing (QS) is an intercellular signaling and gene regulatory mechanism
that is implicated in food spoilage caused by bacteria. Thus, blocking QS may
suppress QS-controlled phenotypes of these bacteria that are responsible for food
spoilage. Biofilm formation is closely related to bacterial infection, and it is
also a major mechanism responsible for the increased resistance of biofilm
associated bacteria to antimicrobial drugs. Food spoilage and biofilm formation
caused by food-related bacteria have posed a significant problem for the food
industry. Thus, adopting an antibiofilm approach would provide an alternative to
an antibiotic strategy. Dihydrocoumarin is a compound that is derived from
coumarin, a known natural QS inhibitor that has been used as an additive in food.
Hafnia alvei is a spoilage bacterium; H. alvei H4 was isolated from ready-to-eat
sea cucumber. Considering that QS and biofilm are often closely linked, this
research aimed to detect the effect of dihydrocoumarin on the production of
violacein by Chromobacterium violaceum 026 and to evaluate the inhibitory effect
of dihydrocoumarin on the formation of biofilm by H. alvei H4 by using violacein
and crystal violet assays. C. violaceum 026 treated with dihydrocoumarin showed
as much as 70.1% reduction in QS-mediated production of violacein compared with
untreated cells, while exhibiting no significant change in growth. H. alvei H4
treated with dihydrocoumarin displayed 75.8% reduction in swimming motility, and
as much as 89.4% reduction in biofilm formation compared with the nontreated
cells, with the reduction in both cases being dependent on the concentration of
dihydrocoumarin. Scanning electron microscopy showed that dihydrocoumarin could
effectively destroy the biofilm structure of H. alvei H4 and decrease biofilm
density. These findings indicate that dihydrocoumarin can be developed into a new
QS inhibitor or antibiofilm agent for controlling food spoilage and potentially
investigated to increase food safety.
PMID- 28402187
TI - Detection and Isolation of the "Top Seven" Shiga Toxin-Producing Escherichia coli
in Ground Beef: Comparison of RapidFinder Kits to the U.S. Department of
Agriculture Microbiology Laboratory Guidebook Method.
AB - Shiga toxin-producing Escherichia coli (STEC) O157:H7 and serogroups O26, O45,
O103, O111, O121, and O145 are often referred to as the "top seven" STEC, and
these have been declared to be adulterants in beef by the U.S. Department of
Agriculture (USDA) Food Safety and Inspection Service (FSIS). The aim of this
work was to compare the methods described in the USDA FSIS Microbiology
Laboratory Guidebook (MLG) to a two-stage Applied Biosystems RapidFinder STEC
real-time PCR method to test for the top seven STEC in raw ground beef. The
specificity of the RapidFinder workflow that targets non-O157 STEC O-antigen
genes, stx1, stx2, and eae, and E. coli O157-specific targets was determined with
132 top seven STEC strains and 283 exclusion strains. All inclusion strains were
positive, and all exclusion strains gave negative results with the RapidFinder
assay. Strains carrying all of the known variants of stx1 and stx2, including
stx2f and stx2g, were also detected. For RapidFinder analysis, 375-g ground beef
samples spiked with >=4 CFU of representative STEC strains were enriched in 1 L
of tryptic soy broth (TSB) for 10 h at 42 +/- 1 degrees C, and for the MLG
method, 325-g samples were similarly spiked and enriched in 975 mL of modified
TSB for 15 h at 42 +/- 1 degrees C. Following DNA extraction, real-time PCR was
performed using RapidFinder Express software, and for the MLG method, the BAX
Real-Time PCR STEC Suite and the BAX Real-Time E. coli O157:H7 assay were used
with the BAX System Q7 software. Following immunomagnetic separation, presumptive
colonies from modified Rainbow agar O157 plates were confirmed by the real-time
PCR assays. Results of the RapidFinder and BAX assays were similar; all samples
were positive after 10 and 15 h of enrichment, respectively. Isolation and
confirmation of isolates was possible on all samples, except that two O111:NM
strains could not be isolated from a portion of the inoculated samples. Thus, the
RapidFinder system can be used for routine and rapid detection of the top seven
STEC in beef.
PMID- 28402188
TI - Effects of a Worksite Supervised Adapted Physical Activity Program on Trunk
Muscle Endurance, Flexibility, and Pain Sensitivity Among Vineyard Workers.
AB - OBJECTIVES: In viticulture, the prevalence of low back pain is particularly high
among vineyard workers exposed to sustained and awkward postures. One promising
setting for low back pain prevention resides in the implementation of workplace
physical activity. METHODS: This nonrandomized pilot study aims at evaluating the
effects of a worksite supervised adapted physical activity program among 17
vineyard workers volunteered to enter either an intervention group (n = 10) or a
control group (n = 7).The intervention group followed a physical activity program
for 8 weeks involving (1) 15 minutes of warm-up every working day and (2) two
weekly 1-hour adapted physical activity sessions targeting trunk muscle endurance
and flexibility. The control group was advised to continue normal physical
activity. Evaluations were carried out at weeks 0, 4, 8, and 12. Physical
capacity was assessed using flexibility tests for the trunk, along with trunk
muscle flexor and extensor endurance tests. Finally, pain sensitivity was
evaluated by assessing pressure pain thresholds over 14 anatomical locations in
the low back region. RESULTS: For the intervention group, the endurance of the
trunk extensor and flexor significantly increased from baseline to week 8 as well
as the pressure pain thresholds. No change was observed for the control group
over the same period. CONCLUSIONS: These encouraging results in combination with
the high adherence rate set interesting foundations for the promotion of worksite
supervised adapted physical activity and, most likely, offer a new promising
approach to prevent low back pain among vineyard workers.
PMID- 28402189
TI - Going non-viral: the Sleeping Beauty transposon system breaks on through to the
clinical side.
AB - Molecular medicine has entered a high-tech age that provides curative treatments
of complex genetic diseases through genetically engineered cellular medicinal
products. Their clinical implementation requires the ability to stably integrate
genetic information through gene transfer vectors in a safe, effective and
economically viable manner. The latest generation of Sleeping Beauty (SB)
transposon vectors fulfills these requirements, and may overcome limitations
associated with viral gene transfer vectors and transient non-viral gene delivery
approaches that are prevalent in ongoing pre-clinical and translational research.
The SB system enables high-level stable gene transfer and sustained transgene
expression in multiple primary human somatic cell types, thereby representing a
highly attractive gene transfer strategy for clinical use. Here we review several
recent refinements of the system, including the development of optimized
transposons and hyperactive SB variants, the vectorization of transposase and
transposon as mRNA and DNA minicircles (MCs) to enhance performance and
facilitate vector production, as well as a detailed understanding of SB's genomic
integration and biosafety features. This review also provides a perspective on
the regulatory framework for clinical trials of gene delivery with SB, and
illustrates the path to successful clinical implementation by using, as examples,
gene therapy for age-related macular degeneration (AMD) and the engineering of
chimeric antigen receptor (CAR)-modified T cells in cancer immunotherapy.
PMID- 28402190
TI - Perceived Parental Legitimacy as a Moderator of Parent-Child Communication's
Effects on Latina/o Adolescent Substance Use.
AB - Utilizing primary socialization theory (PST) and longitudinal survey data from
381 Latina/o sixth- through eighth-grade students, we hypothesized that four
types of parent anti-substance use messages (i.e., parents' own past substance
use, religious beliefs, respect for family, and peer resistance) would discourage
Latina/o students' substance use, particularly when the students perceived their
parents' anti-substance use messages were legitimate. The results supported
moderation. For Latina/o students who thought that their parents' anti-substance
use messages were legitimate, many of the anti-substance use messages were
negatively related to substance use, but the associations were positive or
nonsignificant for Latina/o students who thought that their parents' anti
substance use messages were not legitimate. The findings extend past work on PST
and anti-substance use parent-child communication, highlighting the importance of
perceived legitimacy and message content.
PMID- 28402191
TI - Sand training: Exercise-induced muscle damage and inflammatory responses to
matched-intensity exercise.
AB - This study compared markers of muscle damage and inflammation elevated by a
matched-intensity interval running session on soft sand and grass surfaces. In a
counterbalanced, repeated-measures and crossover design, 10 well-trained female
athletes completed 2 interval-based running sessions 1 week apart on either a
grass or a sand surface. Exercise heart rate (HR) was fixed at 83-88% of HR
maximum. Venous blood samples were collected pre-, post- and 24 h post-exercise,
and analysed for myoglobin (Mb) and C-reactive protein (CRP). Perceptual ratings
of exertion (RPE) and muscle soreness (DOMS) were recorded immediately post- and
24 h post-exercise. A significant time effect showed that Mb increased from pre-
to post-exercise on grass (p = .008) but not on sand (p = .611). Furthermore,
there was a greater relative increase in Mb on grass compared with that on sand
(p = .026). No differences in CRP were reported between surfaces (p > .05). The
HR, RPE and DOMS scores were not significantly different between conditions (p >
.05). These results suggest that in response to a matched-intensity exercise
bout, markers of post-exercise muscle damage may be reduced by running on softer
ground surfaces. Such training strategy may be used to minimize musculoskeletal
strain while still incurring an equivalent cardiovascular training stimulus.
PMID- 28402192
TI - Farm Safety Practices and Farm Size in New South Wales.
AB - OBJECTIVE: There is some evidence to suggest that safety on small-area farms may
not be high priority due to economic constraints and lack of knowledge. This has
important ramifications for injury and economic burden. The objective of this
research was to conduct a pilot study to investigate whether small- to medium
area farms implement fewer safety practices than large-area farms. METHODS:
Farmers were recruited from farm safety training days, field days, and produce
stores in rural New South Wales (NSW), Australia. Small- and medium-area farms
less than 500 ha (1235 acres) in size were aggregated for analysis and compared
with large-area farms (>=500 ha) for survey items, including safety equipment
owned and used, safety practices protecting children, barriers to improving
safety, and causes of injury. RESULTS: Overall, small/medium-area farms were
found to own less safety equipment and to employ less safety practices than large
area farms. In particular, fewer tractors were fitted with rollover protection
structures, there was less signage, less hearing protection, and fewer machinery
guides. Injury rates were slightly less for small/medium-area farms, particularly
involving vehicles. Small- and medium-area farmers were more likely to report
lack of skills as barriers to making safety improvements. CONCLUSION: This pilot
study found some evidence that small/medium-area farms implement fewer safety
practices than large-area farms. A larger study is warranted to investigate this
further, with particular focus on barriers and ways to overcome them. This could
have important ramifications for government policies supporting struggling
farmers on small/medium-area farms.
PMID- 28402193
TI - Controlled precipitation for enhanced dissolution rate of flurbiprofen:
development of rapidly disintegrating tablets.
AB - OBJECTIVE: The aim of this work was to investigate the potential of controlled
precipitation of flurbiprofen on solid surface, in the presence or absence of
hydrophilic polymers, as a tool for enhanced dissolution rate of the drug. The
work was extended to develop rapidly disintegrated tablets. SIGNIFICANCE: This
strategy provides simple technique for dissolution enhancement of slowly
dissolving drugs with high scaling up potential. METHODS: Aerosil was dispersed
in ethanolic solution of flurbiprofen in the presence and absence of hydrophilic
polymers. Acidified water was added as antisolvent to produce controlled
precipitation. The resultant particles were centrifuged and dried at ambient
temperature before monitoring the dissolution pattern. The particles were also
subjected to FTIR spectroscopic, X-ray diffraction and thermal analyses. RESULTS:
The FTIR spectroscopy excluded any interaction between flurbiprofen and
excipients. The thermal analysis reflected possible change in the crystalline
structure and or crystal size of the drug after controlled precipitation in the
presence of hydrophilic polymers. This was further confirmed by X-ray
diffraction. The modulation in the crystalline structure and size was associated
with a significant enhancement in the dissolution rate of flurbiprofen. Optimum
formulations were successfully formulated as rapidly disintegrating tablet with
subsequent fast dissolution. CONCLUSIONS: Precipitation on a large solid surface
area is a promising strategy for enhanced dissolution rate with the presence of
hydrophilic polymers during precipitation process improving the efficiency.
PMID- 28402195
TI - The Oral Health Needs of Wisconsin Farmers and the Need for Patient Activation: A
Pilot Study.
AB - OBJECTIVES: This study aimed to determine the level of oral health need of
Wisconsin farmers based on sociodemographic variables, perceived oral health, and
actual oral health, and to evaluate the effectiveness of a dental hygiene patient
activation intervention. METHODS: Oral health screenings were administered by
calibrated dental hygienists to 60 Wisconsin farmers attending the 2016 Wisconsin
Farm Technology Days. Study participants self-administered the Oral Health
Inventory Profile-14 survey and participated in an Adult Basic Screening Survey.
Validity and reliability of both instruments have been established in previous
studies. A follow-up phone call for Wisconsin farmers with a moderate- to high
risk oral health condition determined study participants followed the dental
hygiene recommendations signified if study participants followed the dental
hygiene recommendations and if patient activation had been achieved. RESULTS:
Study participants represented Wisconsin farmers (N = 60; n = 32 men, n = 28
women) with an average age range between 50 and 60 years old. The Oral Health
Impact Profile-14 survey results indicated that this group of Wisconsin farmers
did not perceive themselves to have an oral health problem. The Adult Basic
Screening Survey results also indicated that the majority of study participants
did not currently have active oral disease. There were 32% (n = 19) who qualified
for follow-up phone call, with 15% (n = 3) seeking oral health care based on the
dental hygiene recommendation. Significant associations between sociodemographic
variables and actual oral health were not found, and the null hypotheses were not
rejected. CONCLUSIONS: Findings suggest that this group of Wisconsin farmers is
receiving regular oral health care and patient activation despite literature
suggesting that farmers and rural individuals might face unique barriers to
health and oral health care.
PMID- 28402194
TI - Words can hurt: The effects of physical and psychological partner violence on
condom negotiation and condom use among young women.
AB - Physical and psychological intimate partner violence (IPV) are prevalent on
college campuses and may affect young women's condom use behavior. This study
explored condom negotiation as a mediator of the relation of physical and
psychological IPV to condom use among college women. A total of 235 heterosexual
college women were recruited during September 2012-May 2013. Participants
completed online questionnaires assessing lifetime history of IPV, frequency of
condom negotiation, and use of condoms during the last 30 days. Specific forms of
psychological IPV were related to less condom use. This association was mediated
by condom negotiation, such that those who had experienced psychological IPV were
less likely to negotiate condom use, and as a result, less likely to report using
condoms in the past 30 days. Campus-based sexual health efforts should consider
the relation of psychological IPV to condom negotiation and condom use and offer
skills to promote condom negotiation among college women to increase condom use
and reduce their risk of sexually transmitted infections.
PMID- 28402196
TI - Mice Antibody Response to Conserved Nonadjuvanted Multiple Antigenic Peptides
Derived from E1/E2 Regions of Hepatitis C Virus.
AB - Synthetic peptides are one of the hepatitis C virus (HCV)-specific small
molecules that have antiviral activity and represent a target for HCV vaccine.
This study aims to determine the lowest concentration of adjuvanted and non
adjuvanted (multiple antigenic peptide [MAP]) form of three conserved HCV
envelope peptides that can induce murine immunogenic responses and evaluate the
neutralization capacities of the generated antibodies (Abs) against HCV in
cultured Huh7.5 cells. In this study, three HCV synthetic peptides, E1 peptide
(a.a 315-323) and E2 peptides (a.a 412-419 and a.a 516-531) were synthesized.
Female Balb/c mice were immunized with different concentration of either
adjuvanted linear peptides or nonadjuvanted MAP peptides to determine the lowest
dose that generates Ab responses enough to confer viral neutralization in vitro.
The humoral responses targeting these peptides in immunized mice sera were
measured by enzyme-linked immunosorbent assay (ELISA). Viral neutralization
capacities of the generated mice Abs were assessed using Huh7.5 cells infected
with the HCVcc infectious system (J6/JFH-1). The results of this study showed
that the MAPs induce higher Ab titers than adjuvanted linear peptides after 4
weeks of immunization (p = 0.003). The viral neutralization experiments showed
that the immunized mice sera contain anti E1/E2 Abs that blocked HCVcc (J6/JFH-1)
entry into Huh7.5 cells. In conclusion, the three HCV envelope MAP peptides are
more immunogenic and produce higher neutralizing Abs than linear peptides;
therefore, they can be essential components for HCV vaccine.
PMID- 28402197
TI - Minimal residual disease or cure in MPNs? Rationales and perspectives on
combination therapy with interferon-alpha2 and ruxolitinib.
AB - INTRODUCTION: The therapeutic landscape of the Philadelphia-negative
myeloproliferative neoplasms (MPNs) is markedly changing consequent to the
development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with
myelofibrosis (MF) and patients with polycythemia vera (PV) who develop
refractoriness or intolerance to hydroxyurea. The use of Interferon-alpha2 (IFN)
is rapidly expanding in several countries, based upon favourable safety and
efficacy profiles in several single-arm studies during the last 30 years,
displaying complete hematological remissions in a large proportion of patients, a
reduction in the JAK2V617 F and CALR mutational burden and in a subset of
patients with PV with normalisation of the bone marrow after long-term treatment
even being sustained for several years after discontinuation of IFN. To this end
the concept of chronic inflammation as the driving force for MPN disease
progression is being increasingly recognized. This novel concept has initiated
phase II studies in patients with PV and MF of combination therapy with IFN and
RUX. Areas covered and Expert commentary: Herein we highlight the background, the
rationales and perspectives for this novel combinatorial approach which is
foreseen as the most encouraging and promising treatment for patients with MPNs -
hopefully with the potential of cure - at least operational cure - in a subset of
patients.
PMID- 28402198
TI - Ventral longitudinal intraspinal fluid collection: Rare presentation as brachial
amyotrophy and intracranial hypotension.
AB - CONTEXT: Ventral longitudinal intraspinal fluid collection (VLISFC) presenting as
hand amyotrophy has been described only in a few cases and there are no reports
on associated intracranial CSF hypovolemia (ICH). We describe the clinical and
imaging findings of a case with combined brachial amyotrophy and ICH secondary to
VLISFC. FINDINGS: A 31 year old man presented with severe positional neck
discomfort, radiating pain, progressive asymmetrical wasting and weakness of
distal upper limbs. Contrast Magnetic Resonance Imaging (MRI) of the spine
demonstrated a ventral extradural intraspinal fluid collection extending from
upper border of C6 to lower border of T3 vertebra with pockets of dorsal
collection. Three-dimensional constructive interference in steady state (CISS 3D)
used in spinal imaging for identification of CSF leak corroborated with the
extent seen on T2 sagittal sections; however, the site of the leak was not
identified. After a year he developed disturbing postural headache which was
relieved in recumbent position. Follow up MRI of brain was normal while spine
demonstrated significant cervical cord atrophy and bilateral cord white matter
hyperintensities. Conclusion / Clinical Relevance: We report this unusual case
where local compression by VLISFC located at the cervical and upper thoracic
level not only caused distal bi-brachial amyotrophy mimicking Hirayama disease
but also led to secondary intracranial hypotension. An early identification and
intervention could possibly have prevented the onset of ICH.
PMID- 28402199
TI - From Menarche to Menopause: Understanding Multigenerational Reproductive Health
Milestones.
AB - Our study aims at understanding multigenerational communication among
grandmothers, mothers, and daughters experiencing reproductive health transitions
from menarche to menopause. Thirty women, 10 triads of grandmothers, mothers, and
daughters, participated in narrative interviews to recount their menarche and
menopause experiences. Analysis was read using a multilayered approach to
interpret discourse positioned from self, reflexive others, and those stories
informed by societal meanings. Four dialectical themes informed by generational
discursive shifts in talk included (1) covert versus overt talk, (2) recollection
of versus indifference to menarche, (3) bound to versus freedom from
menstruation, and (4) controlling versus managing bodily changes. The theoretical
significance of this piece indicates a slight, transformative change in how
messages about menarche and menstruation are communicated or passed down from one
generation to the next.
PMID- 28402200
TI - Elimination of dioxins in milk by dairy cows after the long-term intake of
contaminated sugar beet pellets.
AB - Dried feed materials, such as sugar beet pellets, may be a source of high levels
of PCDD/Fs. The studies followed up dioxin congener elimination from contaminated
milk (5.02 +/- 1.39 pg WHO PCDD/F-PCBs-TEQ g-1 fat) up to 338 days after
withdrawal of polluted feed ingredient (4.37 +/- 0.25 ng PCDD/F/DL-PCBs-TEQ kg-1
feed). The main objectives of the study were to estimate the length of the time
needed to achieve an acceptable PCDD/F milk level as set by European Union law,
to track the fate of the PCDD/F congeners, and to assess the potential risk for
consumers associated with long-term consumption of contaminated milk. After
approximately 200 days, the PCDD/F levels reached ML (2.5 pg WHO-TEQ g-1 fat),
then decreased to the action level after more than 300 days (1.75 pg WHO-TEQ g-1
fat) for most of cows. The potential risk of PCDD/F/DL-PCBs intake was
characterised by comparing the theoretically calculated weekly and monthly
intakes with the toxicological reference values (TRVs). The dioxin intake for the
average adult and high-milk consumers did not exceed half of any of the TRVs
applied (TWI, PTMI). The consumption of milk by children in the amount
recommended by nutritionists (500 ml day-1) resulted in an exposure equal to 317%
TWI and 275% PTMI.
PMID- 28402201
TI - Bullying and cyberbullying in adulthood and the workplace.
AB - Two studies generated profiles of cyberbullying/cyberincivility and traditional
bullying/incivility in adults, particularly within the workplace. In Study 1, 20%
of 3,699 participants had the majority of cyberbullying victimization and 7.5%
had the majority of traditional bullying victimization occur in adulthood, with
30% saying they were bullied at work. Relationships between bullying and negative
outcomes were found. Because of the clear evidence of bullying and cyberbullying
in the workplace in Study 1, Study 2 addressed the relationship of these
constructs to workplace incivility. Workplace face-to-face incivility and
bullying were related among 321 participants, as were workplace cyberbullying and
cyberincivility. Face-to-face incivility was more common than online incivility,
face-to-face bullying, or online bullying, yet all four behaviors were associated
with negative outcomes. Differences in intentionality, acceptability, and
severity were observed, with workplace face-to-face bullying perceived as the
most severe and having the greatest intentionality to harm. These results
emphasize the importance of studying bullying among adults, and highlight the
conceptual independence of bullying and incivility. Correlates of workplace
aggression are discussed using job demands-resources theory.
PMID- 28402202
TI - Correlations Between MMPs and TIMPs Levels in Aqueous Humor from High Myopia and
Cataract Patients.
AB - PURPOSE: To study the relationships between matrix metalloproteinases (MMP)-2,
MMP-3, and tissue inhibitors of matrix metalloproteinases (TIMP)-1, TIMP-2, and
TIMP-3 aqueous humor levels in patients with high myopia or cataract. MATERIALS
AND METHODS: MMPs and TIMPs protein levels in 65 aqueous humor samples collected
from patients with high myopia or cataract during cataract or clear lens
extraction surgery were measured with the Luminex xMAP Technology. The
relationship between MMPs and TIMPs levels was analyzed with Spearman's
correlation test. RESULTS: MMP-2 levels, but not MMP-3 levels, were increased in
the aqueous humor from high-myopia patients. Levels of TIMP-1, -2, and -3 were
positively and very significantly correlated with the MMP-2 levels (TIMP-1:
r=0.626, p < 0.001; TIMP-2: r = 0.545, p < 0.001; TIMP-3: r = 0.439, p < 0.001).
TIMP-2 and-3 levels did not significantly correlate with MMP-3 levels (TIMP-2: r
= 0.175, p > 0.05; TIMP-3: r = 0.127, p > 0.05) and TIMP-1 levels only marginally
correlated with MMP-3 levels (r = 0.278, 0.01< P < 0.05). CONCLUSIONS: Compared
to the present findings with the relationship of MMPs and TIMPs in other fields
of medicine, our results are consistent with the homeostasis hypothesis that the
increase of TIMPs serves as a compensation reaction to inhibit the excessive
degradation caused by the increase of MMPs and limits the development of myopia.
PMID- 28402203
TI - Hydration and Cooling Practices Among Farmworkers in Oregon and Washington.
AB - OBJECTIVES: Although recommendations for preventing occupational heat-related
illness among farmworkers include hydration and cooling practices, the extent to
which these recommendations are universally practiced is unknown. The objective
of this analysis was to compare hydration and cooling practices between
farmworkers in Oregon and Washington. METHODS: A survey was administered to a
purposive sample of Oregon and Washington farmworkers. Data collected included
demographics, work history and current work practices, hydration practices,
access and use of cooling measures, and headwear and clothing worn. RESULTS:
Oregon farmworkers were more likely than those in Washington to consume beverages
containing sugar and/or caffeine. Workers in Oregon more frequently reported
using various cooling measures compared with workers in Washington. Availability
of cooling measures also varied between the two states. CONCLUSIONS: These
results highlight the large variability between workers in two states regarding
access to and use of methods to stay cool while working in the heat.
PMID- 28402204
TI - Evaluation of the MiStent sustained sirolimus eluting biodegradable polymer
coated stent for the treatment of coronary artery disease: does uniform sustained
abluminal drug release result in earlier strut coverage and better safety
profile?
AB - INTRODUCTION: Treatment of coronary artery disease has made strides over the last
decades. Development of drug eluting stents (DES), coated with a polymer layer
and an anti-proliferative drug to reduce neointimal hyperplasia, has reduced the
incidence of in-stent-restenosis relative to treatment with bare metal stents.
Patients treated with first generation DES more likely suffer from (very) late
events which can be cause by the permanent presence of a polymer. Therefore
second generation DES with more biocompatible coatings, and third generation DES,
with very thin struts coated with biodegradable polymers, were developed. Areas
covered: The MiStent SES is one of these third generation DES and is designed to
limit the duration of polymer exposure, optimize coronary vessel healing and more
precisely and consistently control drug elution to improve safety and clinical
outcomes. This review provides a detailed description of the technique behind the
MiStent SES, and describes the pre-clinical and clinical trials conducted with
this device to date. Expert commentary: Recent clinical trials have shown non
inferiority of very thin strut biodegradable polymer coated DES compared to
durable polymer coated DES, whilst maintaining an excellent safety profile.
Longer follow-up, to see the real potential benefits of these devices, is
mandatory however.
PMID- 28402205
TI - Nonionic surfactant based thymoquinone loaded nanoproniosomal formulation: in
vitro physicochemical evaluation and in vivo hepatoprotective efficacy.
AB - CONTEXT: The present study was carried out to formulate thymoquinone proniosomal
formulation (TQP) and evaluate their efficacy in methotrexate (Mtx) induced
hepatotoxicity in rats. OBJECTIVE: The objective of the study was to explore a
new therapeutic approach focusing on hepatoprotective activity using thymoquinone
proniosomal formulation. MATERIAL AND METHODS: TQP was formulated using span60,
cholesterol and phospholipid by film hydration technique. The animals were
divided into six groups with five animals each receiving different treatments for
7 days. On the 8th day, rats were anesthetized with ether, blood samples were
withdrawn, livers were dissected out for biochemical tests and histopathological
examinations. RESULTS AND DISCUSSION: The size of vesicle was found to be in the
nanometric range with higher entrapment efficiency. The high entrapment
efficiency is probably due to the lipophilic character of TQ. The morphological
structure showed the outline and core of the well-identified spherical vesicle,
and also displaying the retention of sealed vesicular structure. The release of
TQ from developed formulation was found to be significantly higher compared to
control. Mtx treated rats showed significant elevation in ALT, AST, ALP and
TBARs, whereas, TQP treated group showed significant reduction. CONCLUSION: The
developed formulation (TQP) significantly inhibited the elevated levels of serum
marker enzymes and showed improved histopathological deformities.
PMID- 28402206
TI - Second cancers in survivors of plasmacytoma of bone in the U.S.A: a SEER database
analysis.
PMID- 28402208
TI - A dynamic approach for outpatient scheduling.
AB - AIMS: Patient no-show is a recurrent problem in medical centers and, in
conjunction with cancellation of appointments, often results in loss of
productivity and excessive patient time to appointment. The purpose of this study
was to develop a dynamic procedure for scheduling patients within an outpatient
clinic where patients are expected to have multiple appointments, such as
physical therapy, occupational therapy, primary care, and dentistry. METHODS:
This retrospective study involved the year 2014 de-identified patient records
from an outpatient clinic affiliated with a large university hospital. A number
of patient characteristics, appointment data, and historical attendance records
were examined to determine whether they significantly impacted patients who
missed scheduled appointments (no-shows). Patient attendance behaviors over
multiple appointments were examined to determine whether their no-show and
cancellation patterns differed from one appointment to the next. Decision tree
analysis was applied to those predictors that significantly correlated with
patient attendance behavior to assess the likelihood of a patient no-show. A
sample dynamic appointment scheduling procedure that utilized different
overbooking strategies for different appointment numbers was then developed.
Computer simulation was used to assess the effectiveness of the dynamic procedure
versus two other methods consisting of randomly assigned and uniformly assigned
appointments. RESULTS: The dynamic scheduling procedure resulted in increased
scheduling efficiency through overbooking but with less than 5% risk of
appointment conflicts (i.e. two patients showing at the same time), equating to
approximately 0.16 conflicts per clinician per day. It also increased clinic
utilization by about 6.7%. It consistently outperformed the other two methods
with respect to the percentage of appointment conflicts. LIMITATIONS: The study
is limited with respect to potential clinician cost increase resulting from
possible appointment conflicts. A second limitation is that patients experiencing
appointment conflicts might not wait for treatment, resulting in potential loss
of revenue. A third limitation is that the model does not take into account
patient satisfaction, nor the ethics of overbooking patients. CONCLUSIONS: A
dynamic appointment scheduling procedure was developed using actual patient
characteristics. The procedure resulted in creation of more efficient appointment
schedules thereby increasing the clinic utilization.
PMID- 28402209
TI - Culturomics: A New Kid on the Block of OMICS to Enable Personalized Medicine.
AB - This innovation analysis highlights the underestimated and versatile potential of
the new field of culturomics and examines its relation to other OMICS system
sciences such as infectiomics, metabolomics, phenomics, and pharmacomicrobiomics.
The advent of molecular biology, followed by the emergence of various disciplines
of the genomics, and most importantly metagenomics, brought about the sharp
decline of conventional microbiology methods. Emergence of culturomics has a
natural synergy with therapeutic and clinical genomic approaches so as to realize
personalized medicine. Notably, the concept of culturomics expands on that of
phenomics and allows a reintroduction of the culture-based phenotypic
characterization into the 21st century research repertoire, bolstered by robust
technology for automated and massive execution, but its potential is largely
unappreciated at present; the few available references show unenthusiastic
pursuit and in narrow applications. This has not to be so: depending on the
specific brand of culturomics, the scope of applications may extend to medicine,
agriculture, environmental sciences, pharmacomicrobiomics, and biotechnology
innovation. Moreover, culturomics may produce Big Data. This calls for a new
generation of data scientists and innovative ways of harnessing and valorizing
Big Data beyond classical genomics. Much more detailed and objective
classification and identification of microbiota may soon be at hand through
culturomics, thus enabling precision diagnosis toward truly personalized
medicine. Culturomics may both widen the scope of microbiology and improve its
contributions to diagnostics and personalized medicine, characterizing microbes
and determining their associations with health and disease dynamics.
PMID- 28402210
TI - Virulence Structure Within Populations of Pseudoperonospora cubensis in the
United States.
AB - Cucurbit downy mildew (CDM), caused by the obligate oomycete Pseudoperonospora
cubensis, has resurged around the world during the past three decades. A new
pathotype or genetic recombinant of P. cubensis have been suggested as possible
reasons for the resurgence of CDM in the United States in 2004. In total, 22
isolates collected between 2004 and 2014, mainly in the eastern United States,
were tested for their compatibility with a set of 15 cucurbit host types. The
virulence structure within these isolates was evaluated on a set of 12
differential genotypes from eight genera. All isolates were highly compatible
with the susceptible cultivar of Cucumis sativus, whereas the least compatibility
was observed with Luffa cylindrica and Momordica charantia. Based on the
compatibility with the differential host set, five pathotypes (1, 3, 4, 5, and 6)
were identified among the 22 isolates examined. Pathotypes 1 and 3 had not been
previously described in the United States and isolates of these two new
pathotypes were also compatible with 'Poinsett 76', a cultivar of C. sativus
known to be resistant to CDM prior to 2004. Virulence within the pathogen
population was expressed based on virulence factors, virulence phenotypes, and
virulence complexity. The number of virulence factors ranged from two to eight,
indicating a complex virulence structure, with 77% of the isolates having five to
eight virulence factors. Thirteen virulence phenotypes were identified; the mean
number of virulence factors per isolate and mean number of virulence factors per
virulence phenotype was 5.05 and 5.23, respectively, indicating that complex
isolates and phenotypes contributed equally to the complex virulence structure of
P. cubensis. Gleason and Shannon indices of diversity were 3.88 and 2.32,
respectively, indicating a diverse virulence structure of P. cubensis within the
United States population. The diverse virulence and high virulence complexity
within the pathogen population indicate that host resistance alone in available
cucurbit cultivars will not be effective to control CDM. An integrated approach
involving a combination of fungicide application and introduction of cultivars
with new resistance genes will be required for effective management of CDM.
PMID- 28402211
TI - Metabolomic Study of Chardonnay Grapevines Double Stressed with Esca-Associated
Fungi and Drought.
AB - Esca is a complex grapevine trunk disease associated with fungal infection of the
xylem. However, the inconstancy of external symptoms and the ability of esca
associated fungi to inhabit grapevines without causing apparent disease suggests
that abiotic factors might be involved in the disease. Water stress has been
proposed to be one of the factors influencing esca symptom manifestation but the
specific role played by water stress on esca development is unknown. We conducted
a proton nuclear magnetic resonance spectroscopy-based metabolomic study aiming
at unveiling drought-induced modifications in xylem sap composition that could
contribute to esca-related infection progression. Vitis vinifera 'Chardonnay'
plants were inoculated with Phaeomoniella chlamydospora or Phaeoacremonium
minimum and exposed to water stress. Using this approach, 28 metabolites were
identified in xylem sap. The results show that water stress induces a
concentration increase of most metabolites in xylem sap. An average increase
>100% was found for asparagine, isoleucine, leucine, methionine, phenylalanine,
proline, tyrosine, valine, sarcosine, and trigonelline. The increase of these
compounds seems to be also modulated by fungal infection. This study offers
further support to the putative role of drought in esca expression, and opens new
avenues of research by extending the current knowledge about metabolites possibly
involved in esca disease.
PMID- 28402212
TI - High-Efficiency and High-Throughput On-Chip Exchange of the Continuous Phase in
Droplet Microfluidic Systems.
AB - This article describes an integrated platform for the on-chip exchange of the
continuous phase in droplet microfluidic systems. The drops used in this work are
stabilized by amphiphilic nanoparticles. For some characterizations and
applications of these nanoparticle-stabilized drops, including the measurement of
adsorption dynamics of nanoparticles to the droplet surface, it is necessary to
change the composition of the continuous phase from that used during the droplet
generation process. Thus far, no work has reported the exchange of the continuous
phase for a large number (>1 million) of drops in a microfluidic system. This
article describes the design and characterization of a high-efficiency and high
throughput on-chip exchanger of the continuous phase in a continuous-flow droplet
microfluidic system. The efficiency of exchange was higher than 97%. The
throughput was greater than 1 million drops/min, and this can be increased
further by increasing the number of parallel exchangers used. Because drops are
injected into the exchanger in a continuous-flow manner, the method is directly
compatible with automation to further increase its reliability and potential
scale-up.
PMID- 28402214
TI - Eyeing autophagy and macropinocytosis in the corneal/limbal epithelia.
AB - Macroautophagy/autophagy is vital for cellular homeostasis and helps cells
respond to various stress situations. Macropinocytosis enables cells to
nonselectively engulf and take up large volumes of fluid and is known to supply
amino acids to cells. The stem cell-enriched limbal epithelium has the machinery
necessary to carry out both autophagy and macropinocytosis; however, both
processes are relatively understudied in this tissue. We have demonstrated that
these processes are linked via MIR103-MIR107, a microRNA family that is limbal
epithelial-preferred. Loss of MIR103-MIR107 causes the accumulation of large
vacuoles that originate, in part, from a dysregulation in macropinocytosis via
activation of SRC-RAS signaling. We found that these vacuoles were autophagic in
nature and retained in cells due to inappropriate regulation of end-stage
autophagy. Specifically, MIR103-MIR107 regulates diacylglycerol-PRKC/protein
kinase C and CDK5 (cyclin dependent kinase 5) signaling, which enables DNM1
(dynamin 1) to function in vacuole clearance.
PMID- 28402215
TI - Angry faces are tracked more easily than neutral faces during multiple identity
tracking.
AB - We investigated whether and how emotional facial expressions affect sustained
attention in face tracking. In a multiple-identity and object tracking paradigm,
participants tracked multiple target faces that continuously moved around
together with several distractor faces, and subsequently reported where each
target face had moved to. The emotional expression (angry, happy, and neutral) of
the target and distractor faces was manipulated. Tracking performance was better
when the target faces were angry rather than neutral, whereas angry distractor
faces did not affect tracking. The effect persisted when the angry faces were
presented upside-down and when surface features of the faces were irrelevant to
the ongoing task. There was only suggestive and weak evidence for a facilitatory
effect of happy targets and a distraction effect of happy distractors in
comparison to neutral faces. The results show that angry expressions on the
target faces can facilitate sustained attention on the targets via increased
vigilance, yet this effect likely depends on both emotional information and
visual features of the angry faces.
PMID- 28402213
TI - Engineering and expressing circular RNAs via tRNA splicing.
AB - Circular (circ)RNAs have recently become a subject of great biologic interest. It
is now clear that they represent a diverse and abundant class of RNAs with
regulated expression and evolutionarily conserved functions. There are several
mechanisms by which RNA circularization can occur in vivo. Here, we focus on the
biogenesis of tRNA intronic circular RNAs (tricRNAs) in archaea and animals, and
we detail their use as research tools for orthogonal, directed circRNA expression
in vivo.
PMID- 28402216
TI - A novel and efficient immunoglobulin Y extraction method using poloxamer
polyethylene glycol.
AB - Although many IgY extraction methods (such as polyethylene glycol (PEG)
precipitation method, octanoic acid method, water dilution method, etc.) have
been established, there is still industrial drive and real need in developing
scale-up IgY production methods. Some previous studies have reported that
poloxamer degreasing method shows very good result in IgY extraction from egg
yolk with high degreasing speed, harmlessness, simpleness in operation and
minimal effect on antibody titer. In this study, we developed a new method,
poloxamer-PEG method, to obtain functional IgY with high purity and yield. First,
the delipidation solution was added into the diluted yolk samples, and then the
filtrates were collected from the diluted yolk samples after 3 hr in room
temperature. PEG-6000 was added into the collected filtrates and the mixture was
centrifuged after shaking on the roller mixer for 45 min at room temperature.
Last, the precipitates were resuspended in 1 mL phosphate buffered solution (PBS)
buffer and dialyzed overnight. The results showed that the total protein
concentrate of extractive could reach at 30 mg/mL and the purity of the IgY could
reach at 92.71% with the novel method, which was superior to the PEG
precipitation method and water dilution method.
PMID- 28402217
TI - The DASH Pilot Project: Developing Community-Based Nutrition Education for Older
Adults.
AB - Nutrition-related chronic health conditions among older adults are a growing
concern. In this study, nutrition education materials were created for use in
senior centers by graduate nutrition students. After the materials were
presented, focus groups were conducted with participants (n = 62) to obtain
feedback on the content and presentation. Findings related to the participant's
knowledge of nutrition-related information, strategies to improve future class
sessions, and participant recruitment will be discussed. These findings will be
useful to program administrators as they develop nutrition programs for older
adults who are vulnerable to nutrition-related health problems.
PMID- 28402218
TI - RNA in Disease and development.
PMID- 28402219
TI - Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering:
cell stimulation and drug release.
AB - The dipping-drying procedure and cross-linking method were used to make drug
loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66)
composite porous scaffold, endowing the scaffold controlled drug release
functionality. The prefabricated scaffold was immersed into an aqueous drug/CS
solution in a vacuum condition and then crosslinked by vanillin. The structure,
porosity, composition, compressive strength, swelling ratio, drug release and
cytocompatibility of the pristine and coating scaffolds were investigated. After
coating, the scaffold porosity and pore interconnection were slightly decreased.
Cytocompatibility performance was observed through an in vitro experiment based
on cell attachment and the MTT assay by MG63 cells which revealed positive cell
viability and increasing proliferation over the 11-day period in vitro. The drug
could effectively release from the coated scaffold in a controlled fashion and
the release rate was sustained for a long period and highly dependent on coating
swelling, suggesting the possibility of a controlled drug release. Our results
demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used
as a simple technique to render the surfaces of synthetic scaffolds active, thus
enabling them to be a promising high performance biomaterial in bone tissue
engineering.
PMID- 28402220
TI - Implementation of quality by design toward processing of food products.
AB - Quality by design (QbD) is a systematic approach that begins with predefined
objectives and emphasizes product and process understanding and process control.
It is an approach based on principles of sound science and quality risk
management. As the food processing industry continues to embrace the idea of in
line, online, and/or at-line sensors and real-time characterization for process
monitoring and control, the existing gaps with regard to our ability to monitor
multiple parameters/variables associated with the manufacturing process will be
alleviated over time. Investments made for development of tools and approaches
that facilitate high-throughput analytical and process development, process
analytical technology, design of experiments, risk analysis, knowledge
management, and enhancement of process/product understanding would pave way for
operational and economic benefits later in the commercialization process and
across other product pipelines. This article aims to achieve two major
objectives. First, to review the progress that has been made in the recent years
on the topic of QbD implementation in processing of food products and second,
present a case study that illustrates benefits of such QbD implementation.
PMID- 28402221
TI - An update on the use of C. elegans for preclinical drug discovery: screening and
identifying anti-infective drugs.
AB - INTRODUCTION: The emergence of antibiotic-resistant and -tolerant bacteria is a
major threat to human health. Although efforts for drug discovery are ongoing,
conventional bacteria-centered screening strategies have thus far failed to yield
new classes of effective antibiotics. Therefore, new paradigms for discovering
novel antibiotics are of critical importance. Caenorhabditis elegans, a model
organism used for in vivo, offers a promising solution for identification of anti
infective compounds. Areas covered: This review examines the advantages of C.
elegans-based high-throughput screening over conventional, bacteria-centered in
vitro screens. It discusses major anti-infective compounds identified from large
scale C. elegans-based screens and presents the first clinically-approved drugs,
then known bioactive compounds, and finally novel small molecules. Expert
opinion: There are clear advantages of using a C. elegans-infection based
screening method. A C. elegans-based screen produces an enriched pool of non
toxic, efficacious, potential anti-infectives, covering: conventional
antimicrobial agents, immunomodulators, and anti-virulence agents. Although C.
elegans-based screens do not denote the mode of action of hit compounds, this can
be elucidated in secondary studies by comparing the results to target-based
screens, or conducting subsequent target-based screens, including the genetic
knock-down of host or bacterial genes.
PMID- 28402223
TI - LGBTQ+ Young Adults on the Street and on Campus: Identity as a Product of Social
Context.
AB - Lesbian, gay, bisexual, queer, and other sexual and gender minority (LGBTQ+)
young adults face unique identity-related experiences based on their immersion in
distinctive social contexts. The predominant framework of performing separate
analyses on samples of LGBTQ+ young people by their primary social status
obfuscates more holistic understandings of the role of social context. Using 46
in-depth interviews with LGBTQ+ college students and LGBTQ+ homeless young
adults, we ask: How are LGBTQ+ young adults' capacities for "doing" their gender
and sexual identities shaped by their distinctive social contexts? In developing
their identities, both groups of LGBTQ+ young adults navigated their social
environments to seek out resources and support. Most college students described
their educational contexts as conducive to helping them develop their identities,
or "undo" rigid norms of gender and sexuality. Homeless young adults' social
environments, meanwhile, imposed complex barriers to self-expression that
reinforced more normative expectations of "doing" gender and sexual identities.
PMID- 28402222
TI - Influence of calcium compounds as a compression framework on activated sludge
dewaterability and calorific value.
AB - Calcium compounds have been known to be important for enhancing aggregation and
dewaterability of activated sludge. In this study, the effect of calcium
compounds (CaO, Ca(OH)2, CaCl2, CaSO4 and CaCO3, respectively) on sludge
dewaterability and calorific value was investigated. Upon addition of CaO,
Ca(OH)2, CaCl2, CaSO4 and CaCO3 (112 mg/g dry sludge) into activated sludge,
after compressed filtration the moisture content of sludge was found to be 49.7%,
55.7%, 57.1%, 65.3% and 56.5%, respectively. The addition of calcium compounds
altered the structure of sludge by CaCO3 and Ca(OH)2 production, which improved
sludge filterability and provided frameworks and water passages during
compression. Furthermore, sludge conditioned by CaO addition had better
dewaterability than other calcium compounds. The heat generated from the CaO
hydration and high pH might damage flocs' structure and improve dewaterability of
sludge. Moreover, it was found that excess addition of calcium compounds led to
low calorific value in combustion process. The study concluded that CaO is the
optimal additive for sludge further dewatering by compressed filtration.
PMID- 28402224
TI - Temperament and Social-Emotional Difficulties: The Dark Side of Learning
Disabilities.
AB - The authors compared the relations between general psychological difficulties and
dimensions of temperament in children with and without learning disability (LD).
The main aim was to analyze whether and to what extent children's temperament
dimensions contribute to their general psychological difficulties when LD
diagnosis, age, and gender are taken into account. Participants were 52
elementary school children 7-11 years old (M age = 8.61 years, SD = 1.21 years).
Twenty-six of them had been diagnosed with LD. Six teachers rated their pupils
with and without LD in relation to their general psychological difficulties
(Strengths and Difficulties Questionnaire) and temperament dimensions (Italian
Questionnaires of Temperament). In children with LD, the main dimensions of
temperament with the power to predict general psychological difficulties (i.e.,
emotionality and social orientation) concern these students' relationships with
others (teachers and peers). The findings of the current study draw educators'
and practitioners' attention to the fact that children's temperamental
characteristics may affect how they experience their LD, with significant
implications for their later social adjustment.
PMID- 28402225
TI - The role of attitudinal motivations and collective efficacy on Chinese consumers'
intentions to engage in personal behaviors to mitigate climate change.
AB - The Chinese government has recently pledged to reduce its CO2 emissions by 2030.
Industrial use of energy, however, is just one source of greenhouse gas
emissions. Chinese consumers' more affluent lifestyles also lead to increased
consumption of energy, which can result in greenhouse gas emissions. Based on a
survey of 516 Chinese consumers, the present investigation examined whether their
attitudinal motivations and collective efficacy are related to their intentions
to engage in personal actions that may help reduce greenhouse gas emissions.
Results show that the utilitarian motivation related to the effectiveness of
personal actions to alleviate climate change, motivation to express their moral
values, self-esteem maintenance motivation, and collective efficacy predicted
their attitudes toward these personal actions. Collective efficacy was in turn
predicted by future orientation, norms, and the utilitarian motivation. Finally,
attitudes and collective efficacy were two major considerations that predicted
behavioral intentions. Implications for programs to promote low-carbon actions
and lifestyles among Chinese consumers are discussed.
PMID- 28402226
TI - The first Greek case of heterozygous cerebral autosomal recessive arteriopathy
with subcortical infarcts and leukoencephalopathy: An atypical clinico
radiological presentation.
AB - Cerebral autosomal recessive arteriopathy with subcortical infarcts and
leukoencephalopathy (CARASIL) was previously considered a rare, early-onset
recessive form of small-vessel disease (SVD) caused by biallelic mutations in the
serine protease gene HTRA1 with subsequent loss of its activity. However, very
recently, there is growing interest of research showing heterozygous HTRA1
mutations as causes of SVD with a dominant inheritance pattern. This first Greek
heterozygous CARASIL case with unusual clinico-radiological presentation extends
our very recent knowledge on how heterozygous CARASIL mutations may be associated
with cerebral SVD. Our findings highlight heterozygous HTRA1 mutations as an
important cause of familial SVD, and that screening of HTRA1 should be considered
in all patients with a hereditary SVD of unknown aetiology.
PMID- 28402227
TI - Developing the Cyber Victimization Experiences and Cyberbullying Behaviors
Scales.
AB - The reported prevalence rates of cyber victimization experiences and
cyberbullying behaviors vary. Part of this variation is likely due to the diverse
definitions and operationalizations of the constructs adopted in previous
research and the lack of psychometrically robust measures. Through 2 studies, the
authors developed (Study 1) and evaluated (Study 2) the cyber victimization
experiences and cyberbullying behaviors scales. Participants in Study 1 were 393
(122 boys, 171 girls) and in Study 2 were 345 (153 boys, 192 girls) 11-15-year
olds who completed measures of cyber victimization experiences, cyberbullying
behaviors, face-to-face victimization experiences, face-to-face bullying
behaviors, and social desirability. The 3-factor cyber victimization experiences
scale comprised threat, shared images, and personal attack. The 3-factor
cyberbullying behaviors scale comprised sharing images, gossip, and personal
attack. Both scales demonstrated acceptable internal consistency and convergent
validity.
PMID- 28402229
TI - "People Who Have Something Better To Do Don't Suffer As Much".
PMID- 28402228
TI - Complement Components Are Expressed by Infiltrating Macrophages/Activated
Microglia Early Following Viral Infection.
AB - The individual innate immune components, interleukin-6 and complement component
C3, play a role in the development of acute seizures in the Theiler's murine
encephalomyelitis virus-induced seizure model. We examined the mRNA expression of
various other complement components, cytokines, chemokines, and major
histocompatibility complex antigens both within brain and in isolated ramified
microglial and infiltrating macrophage/activated microglial cell populations over
a time course covering the first 3 days postinfection. We found that complement
component C3 showed the greatest increase in expression in brain of all of the
complement components assayed and its level of expression was higher in
infiltrating macrophages/activated microglia than in ramified microglial cells.
PMID- 28402230
TI - Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and
enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating
miR-125a.
AB - Increasing evidence demonstrated that long non-coding RNA ANRIL serves as a fatal
oncogene in many cancers, including nasopharyngeal carcinoma (NPC). However,
little is known whether ANRIL regulated NPC cell radioresistance. Quantitative
real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA ANRIL
and miR-125a in NPC tissues and cell lines. MTT assay was conducted to measure
the cell viability of CNE2 and HONE1 cells. The apoptotic rate of CNE2 and HONE1
cells was determined by flow cytometry analysis. Colony survival was determined
by clonogenic assay. Luciferase reporter assay was performed to verity the direct
target of miR-125a. LncRNA ANRIL was evidently elevated in NPC tissues and cell
lines. ANRIL inhibition suppressed proliferation, induced apoptosis, and enhanced
radiosensitivity in NPC. Moreover, ANRIL could negatively modulate miR-125a
expression. Furethermore, ANRIL upregulation reserved the inhibited
proliferation, induced apoptosis, and enhanced radiosensitivity triggered by miR
125a overexpression. The expression of lncRNA ANRIL was upregulated in NPC
tissues and cells. Moreover, knockdown of ANRIL repressed proliferation, promoted
apoptosis, and improved radiosensitivity in NPC via functioning as a miR-125a
sponge.
PMID- 28402231
TI - A Comparison of Interventional Approaches for Increasing Power Take-off Shielding
on New York Farms.
AB - OBJECTIVE: Power take-off (PTO) driveline entanglements are a primary source of
injury on US farms. As with many farm injury concerns, hazard control technology
is widely available for mitigating the risk of these entanglements. Despite the
availability of hazard control technology, PTO shields are damaged or missing on
approximately 57% of PTO driveline implements in New York. Given the catastrophic
nature of entanglements and the ready access to safety technology, a better
understanding of what motivates farmers to install or replace PTO shields is
warranted. METHODS: To examine this question, agricultural health and safety
researchers in New York State conducted an initial comparison of PTO shield sales
on farms receiving one of three different interventional approaches. These
included PTO shield audits, a social marketing campaign, and on-farm safety
services. PTO shield purchases were tracked from January 2011 through June 2016
on farms receiving these interventions and on other farms that were not exposed
to interventional strategies. RESULTS: Results indicate that a significantly
higher number of PTO shields were purchased on farms that requested and received
on-farm safety services versus farms that were exposed to PTO shield audits, the
social marketing campaign, or the control group. PTO shield sales were slightly
elevated on farms receiving driveline audits, as compared with control farms
(although these differences were not significant). CONCLUSIONS: No marked
differences in sales were noted between control farms and farms exposed to the
social marketing campaign. Only one of the three interventional strategies (on
farm safety services) approached the number of PTO shield sales necessary to
prevent an entanglement.
PMID- 28402232
TI - Combined exposures of whole-body vibration and awkward posture: a cross sectional
investigation among occupational drivers by means of simultaneous field
measurements.
AB - OBJECTIVE: Multifactorial workloads such as whole-body vibration (WBV), awkward
posture and heavy lifting are potential predictors for low back pain (LBP). In
this study, we investigate the association between LBP and these exposures among
102 professional drivers. METHODS: The combined exposures of WBV and posture are
measured at different workplaces. Health and personal data as well as information
about lifting tasks are collected by a questionnaire. RESULTS: The daily
vibration exposure value (odds ratio 1.69) and an index for awkward posture (odds
ratio 1.63) show significant association with the occurence of LBP. Awkward
posture and heavy lifting appear to be more strongly associated with sick leave
than WBV exposure. Furthermore, a combination of the measurement results of WBV
and awkward posture into one quantity also shows significant correlation to LBP.
CONCLUSION: The combined exposure of WBV and awkward posture can be described in
terms of the daily vibration exposure and the index for awkward posture. This
facilitates work place assessments and future research in this area. Practitioner
Summary: For the first time, quantitative measures combining whole-body vibration
and awkward posture exposures have shown to correlate with the occurrence of low
back pain significantly. This validates the proposed quantities and measurement
methods, which facilitate workplace assessments and assist in the design of
further studies which are necessary to establish a causal exposure-response
relationship.
PMID- 28402233
TI - Torpor Patterns in Desert Hedgehogs (Paraechinus aethiopicus) Represent Another
New Point along a Thermoregulatory Continuum.
AB - Documenting variation in thermoregulatory patterns across phylogenetically and
geographically diverse taxa is key to understanding the evolution of endothermy
and heterothermy in birds and mammals. We recorded body temperature (Tb) in free
ranging desert hedgehogs (Paraechinus aethiopicus) across three seasons in the
deserts of Saudi Arabia. Modal Tb's (35 degrees -36.5 degrees C) were slightly
below normal for mammals but still warmer than those of other hedgehogs. The
single maximum Tb recorded was 39.2 degrees C, which is cooler than maximum Tb's
recorded in most desert mammals. Desert hedgehogs commonly used torpor during
winter and spring but never during summer. Torpor bouts occurred frequently but
irregularly, and most lasted less than 24 h. Unlike daily heterotherms, desert
hedgehogs did occasionally remain torpid for more than 24 h, including one bout
of 101 h. Body temperatures during torpor were often within 2 degrees -3 degrees
C of ambient temperature; however, we never recorded repeated bouts of long,
predictable torpor punctuated by brief arousal periods similar to those common
among seasonal hibernators. Thus, desert hedgehogs can be included on the ever
growing list of species that display torpor patterns intermediate to
traditionally defined hibernators and daily heterotherms. Extant hedgehogs are a
recent radiation within an ancient family, and the intermediate thermoregulatory
pattern displayed by desert hedgehogs is unlike the deeper and more regular
torpor seen in other hedgehogs, suggesting that this may be a derived-as opposed
to ancestral-trait in this subfamily. We suggest that this family (Erinaceidae)
and order (Eulipotyphla) may be important for understanding the evolution of
thermoregulatory patterns among Laurasiatheria and mammals in general.
PMID- 28402235
TI - Intraspecific Variation in and Environment-Dependent Resource Allocation to
Embryonic Development Time in Common Terns.
AB - Embryonic development time is thought to impact life histories through trade-offs
against life-history traits later in life, yet the inference is based on
interspecific comparative analyses only. It is largely unclear whether
intraspecific variation in embryonic development time that is not caused by
environmental differences occurs, which would be required to detect life-history
trade-offs. Here we performed a classical common-garden experiment by incubating
fresh eggs of free-living common terns (Sterna hirundo) in a controlled
incubation environment at two different temperatures. Hatching success was high
but was slightly lower at the lower temperature. While correcting for effects of
year, incubation temperature, and laying order, we found significant variation in
the incubation time embryos required until hatching and in their heart rate.
Embryonic heart rate was significantly positively correlated within clutches, and
a similar tendency was found for incubation time, suggesting that intrinsic
differences in embryonic development rate between offspring of different parents
exist. Incubation time and embryonic heart rate were strongly correlated: embryos
with faster heart rates required shorter incubation time. However, after
correction for heart rate, embryos still required more time for development at
the lower incubation temperature. This suggests that processes other than
development require a greater share of resources in a suboptimal environment and
that relative resource allocation to development is, therefore, environment
dependent. We conclude that there is opportunity to detect intraspecific life
history trade-offs with embryonic development time and that the resolution of
trade-offs may differ between embryonic environments.
PMID- 28402234
TI - Apple Snail Perivitellin Precursor Properties Help Explain Predators' Feeding
Behavior.
AB - In contrast with vitellogenin maturation, it is unknown whether gastropod
perivitellin precursors are subject to large structural changes. The gastropod
reproductive tract includes an accessory organ, the albumen gland (AG), that
produces and secretes perivitelline fluid. In the apple snail Pomacea
canaliculata, the large, reddish-pink AG provides eggs with perivitellins that
are defensive against predators. Although the AG makes a considerable
contribution to apple snail biomass, field observations indicate that it is
rejected by avian and mammalian predators, although the underlying reason remains
unknown. By analyzing the structure-function properties of P. canaliculata
perivitellin precursors, we provide insight into perivitellin maturation and its
relationship with apple snail predator feeding behavior. Structural analysis
using small-angle X-ray scattering, absorption and fluorescence spectroscopy,
circular dichroism, electrophoresis, chromatography, and partial proteolysis
showed that the size, shape, and structure of perivitellin precursors resemble
those of egg mature forms. Functional analysis indicates that the precursors of
the defensive perivitellins ovorubin (PcOvo) and perivitellin-2 (PcPV2) are
highly stable and antinutritive, withstanding proteinase digestion and displaying
structural stability of their quaternary structure under a wide pH range (4.0
10.0). Furthermore, AG extracts limit a predator's ability to digest nutrients
and are toxic to mice (median lethal concentration 96 h after administration: 5.9
mg/kg). Treated mice displayed neurologic signs similar to those produced by egg
PcPV2. Results indicate that apple snails store active precursors of egg proteins
inside the AG, providing evidence that gastropod perivitellin precursors do not
experience the large structural processing of invertebrate vitellogenin
maturation. These defensive proteins provide the apple snail AG with neurotoxic,
antinutritive, and antidigestive activity, a likely explanation for the
predators' feeding behavior.
PMID- 28402236
TI - Zika Virus Infection and Associated Neurologic Disorders in Brazil.
PMID- 28402238
TI - Data Authorship as an Incentive to Data Sharing.
PMID- 28402237
TI - Bioresorbable Scaffolds versus Metallic Stents in Routine PCI.
AB - BACKGROUND: Bioresorbable vascular scaffolds were developed to overcome the
shortcomings of drug-eluting stents in percutaneous coronary intervention (PCI).
We performed an investigator-initiated, randomized trial to compare an everolimus
eluting bioresorbable scaffold with an everolimus-eluting metallic stent in the
context of routine clinical practice. METHODS: We randomly assigned 1845 patients
undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients)
or a metallic stent (921 patients). The primary end point was target-vessel
failure (a composite of cardiac death, target-vessel myocardial infarction, or
target-vessel revascularization). The data and safety monitoring board
recommended early reporting of the study results because of safety concerns. This
report provides descriptive information on end-point events. RESULTS: The median
follow-up was 707 days. Target-vessel failure occurred in 105 patients in the
scaffold group and in 94 patients in the stent group (2-year cumulative event
rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval
[CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan-Meier estimates in
time-to-event analyses. Cardiac death occurred in 18 patients in the scaffold
group and in 23 patients in the stent group (2-year cumulative event rates, 2.0%
and 2.7%, respectively), target-vessel myocardial infarction occurred in 48
patients in the scaffold group and in 30 patients in the stent group (2-year
cumulative event rates, 5.5% and 3.2%), and target-vessel revascularization
occurred in 76 patients in the scaffold group and in 65 patients in the stent
group (2-year cumulative event rates, 8.7% and 7.5%). Definite or probable device
thrombosis occurred in 31 patients in the scaffold group as compared with 8
patients in the stent group (2-year cumulative event rates, 3.5% vs. 0.9%; hazard
ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS: In this preliminary
report of a trial involving patients undergoing PCI, there was no significant
difference in the rate of target-vessel failure between the patients who received
a bioresorbable scaffold and the patients who received a metallic stent. The
bioresorbable scaffold was associated with a higher incidence of device
thrombosis than the metallic stent through 2 years of follow-up. (Funded by
Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077 .).
PMID- 28402239
TI - Device Thrombosis with Bioresorbable Scaffolds.
PMID- 28402240
TI - Scientific Drought, Golden Eggs, and Global Leadership - Why Trump's NIH Funding
Cuts Would Be a Disaster.
PMID- 28402241
TI - An FDA Commissioner for the 21st Century.
PMID- 28402242
TI - Scott Gottlieb and the Credibility of U.S. Therapeutics.
PMID- 28402243
TI - Use of the National Heart, Lung, and Blood Institute Data Repository.
AB - BACKGROUND: Research on data sharing from clinical trials has focused on
elucidating perceptions, barriers, and attitudes among trialists and study
participants with respect to sharing data. However, little information exists
regarding utilization or associated publication of articles once clinical trial
data have been widely shared. METHODS: We analyzed administrative records of
investigator requests for data access, linked publications, and bibliometrics to
describe the use of the National Heart, Lung, and Blood Institute data
repository. RESULTS: From January 2000 through May 2016, a total of 370
investigators requested data from 1 or more clinical trials. Requests for trial
data have been increasing, with 195 investigators (53%) initiating requests
during the last 4.4 years of the study period. The predominant reason for
requesting data was post hoc secondary analysis of new questions (72%), followed
by analytic or statistical approaches to clinical trials (9%) and meta-analyses
or pooled study research (7%). Of 172 requests with online project descriptions,
only 2 requests were initiated for reanalysis of primary-outcome findings. Data
from 88 of 100 available clinical trials were requested at least once, and the
median time from repository availability to first request was 235 days. A total
of 277 articles were published on the basis of data from 47 trials. Citation
metrics from 224 articles indicated that half of the publications have cumulative
citations that rank in the top 34% normalized for subject category and year of
publication. CONCLUSIONS: Demand for trial data for secondary analysis has been
increasing. Requesting data for the a priori purpose of reanalysis or
verification of original findings was rare.
PMID- 28402244
TI - Medical Liability - Prospects for Federal Reform.
PMID- 28402246
TI - Resident Duty Hours and Medical Education Policy - Raising the Evidence Bar.
PMID- 28402247
TI - The Future of Transgender Coverage.
PMID- 28402245
TI - Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.
AB - BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is
controversial. We aimed to determine whether levothyroxine provided clinical
benefits in older persons with this condition. METHODS: We conducted a double
blind, randomized, placebo-controlled, parallel-group trial involving 737 adults
who were at least 65 years of age and who had persisting subclinical
hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine
level within the reference range). A total of 368 patients were assigned to
receive levothyroxine (at a starting dose of 50 MUg daily, or 25 MUg if the body
weight was <50 kg or the patient had coronary heart disease), with dose
adjustment according to the thyrotropin level; 369 patients were assigned to
receive placebo with mock dose adjustment. The two primary outcomes were the
change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related
quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with
higher scores indicating more symptoms or tiredness, respectively; minimum
clinically important difference, 9 points). RESULTS: The mean age of the patients
was 74.4 years, and 396 patients (53.7%) were women. The mean (+/-SD) thyrotropin
level was 6.40+/-2.01 mIU per liter at baseline; at 1 year, this level had
decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU
per liter in the levothyroxine group (P<0.001), at a median dose of 50 MUg. We
found no differences in the mean change at 1 year in the Hypothyroid Symptoms
score (0.2+/-15.3 in the placebo group and 0.2+/-14.4 in the levothyroxine group;
between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the
Tiredness score (3.2+/-17.7 and 3.8+/-18.4, respectively; between-group
difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine
were seen on secondary-outcome measures. There was no significant excess of
serious adverse events prespecified as being of special interest. CONCLUSIONS:
Levothyroxine provided no apparent benefits in older persons with subclinical
hypothyroidism. (Funded by European Union FP7 and others; TRUST
ClinicalTrials.gov number, NCT01660126 .).
PMID- 28402249
TI - The Art of Repeal - Republicans' Health Care Reform Muddle.
PMID- 28402248
TI - Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.
AB - BACKGROUND: A protein that is expressed on capillary endothelial cells, called
GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding
protein 1), binds lipoprotein lipase and shuttles it to its site of action in the
capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from
reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma
levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides,
and severe hypertriglyceridemia (chylomicronemia). During the characterization of
a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma
samples (both from patients with chylomicronemia) that contained an interfering
substance that made it impossible to measure GPIHBP1. That finding raised the
possibility that those samples might contain GPIHBP1 autoantibodies. METHODS:
Using a combination of immunoassays, Western blot analyses, and
immunocytochemical studies, we tested the two plasma samples (as well as samples
from other patients with chylomicronemia) for the presence of GPIHBP1
autoantibodies. We also tested the ability of GPIHBP1 autoantibodies to block the
binding of lipoprotein lipase to GPIHBP1. RESULTS: We identified GPIHBP1
autoantibodies in six patients with chylomicronemia and found that these
autoantibodies blocked the binding of lipoprotein lipase to GPIHBP1. As in
patients with GPIHBP1 deficiency, those with GPIHBP1 autoantibodies had low
plasma levels of lipoprotein lipase. Three of the six patients had systemic lupus
erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a
baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had
severe but transient chylomicronemia. Two of the patients with chylomicronemia
and GPIHBP1 autoantibodies had a response to treatment with immunosuppressive
agents. CONCLUSIONS: In six patients with chylomicronemia, GPIHBP1 autoantibodies
blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby
interfering with lipoprotein lipase-mediated processing of triglyceride-rich
lipoproteins and causing severe hypertriglyceridemia. (Funded by the National
Heart, Lung, and Blood Institute and the Leducq Foundation.).
PMID- 28402250
TI - Zoonotic Cutaneous Leishmaniasis Prevalence Among Farmers in Central Tunisia,
2014.
AB - OBJECTIVE: Zoonotic cutaneous leishmaniasis (ZCL) is endemic in central Tunisia
and is more prevalent in rural agricultural areas. The aim of this work was to
determine ZCL prevalence among farmers and to test their availability to take
ownership of the problem and participate actively to fight and address the
disease. METHODS: A sample of farmers from Sidi Bouzid, central Tunisia, was
selected randomly. Farmers were interviewed using a standardized questionnaire
about ZCL lesion occurrence, its date of onset among family members, and the
farmers' availability to contribute to fighting this disease. RESULTS: ZCL
occurred in at least one of the family members of 38.5% interviewed farmers. The
disease was endemic with recurrent epidemics every 4 or 5 years. ZCL among
farmers was associated with irrigation management. With regard to ZCL preventive
measures, the majority of farmers agreed and expressed willingness to collaborate
(93.1%), to follow health care facilities instructions (73.1%), and to join the
nongovernmental organization (NGO) (56.9%). However, they did not agree to reduce
irrigation activities mainly at night, to live far from their irrigated fields,
or to sleep out of their houses at night. CONCLUSIONS: ZCL is more prevalent in
farmers engaged in irrigation activities. Farmers are not agreeable to reducing
their activity to avoid exposure to the sand fly bites. Thus, population
involvement and commitment is required to implement effective control measures to
fight and address ZCL.
PMID- 28402251
TI - Do rats see like we see?
AB - Like primates, the rat brain areas thought to be involved in visual object
recognition are arranged in a hierarchy.
PMID- 28402253
TI - Immunoregulatory role of B lymphocytes in alloresponse to kidney transplant.
AB - B cells are a group of diverse phenotype and function subsets, which can both
stimulate and inhibit the immune response to an allograft. They participate in
the rejection process by influencing differentiation, proliferation and effector
functions of T lymphocytes. B cells injure the graft via the ADCC (antibody
dependent cellular cytotoxicity) reaction and humoral rejection through
plasmocyte production of donor-specific antibodies. A converse, suppressive mode
of B cells can attribute to the development of tolerance and protect the graft
from rejection. This function is provided by the regulatory B cells, which
negatively control the immune response by producing suppressor cytokines (IL-10,
IL-35, TGF-beta), natural antibodies and through cellular interactions. In effect
they inhibit the development of Th1 and Th17 effector cells, and induce
differentiation of regulatory T cells. Operational immune tolerance in human
kidney transplant recipients was associated with increased number of naive and
transitional B cells of regulatory function, and increased gene expression for
differentiation of B cells. However, in chronic alloantibody transplant rejection
the distorted distribution and function of regulatory B cells was found, which
implies their pivotal role in graft tolerance. Currently, the immunosuppressive
regimens unselectively inhibit the activity of T and B cells, by interfering with
their effector and immunoregulatory functions. They do not fully control the
chronic rejection reaction, which is the major cause of graft loss. Comprehension
of the mechanisms of immunologic homeostasis dependent on B cells can help
develop immunosuppressive protocols targeted at tolerance.
PMID- 28402252
TI - Constitutive activation of kappa opioid receptors at ventral tegmental area
inhibitory synapses following acute stress.
AB - Stressful experiences potently activate kappa opioid receptors (kappaORs).
kappaORs in the ventral tegmental area regulate multiple aspects of dopaminergic
and non-dopaminergic cell function. Here we show that at GABAergic synapses on
rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress
induces prolonged activation of kappaORs. This is mediated by activation of the
receptor during the stressor followed by a persistent, ligand-independent
constitutive activation of the kappaOR itself. This lasting change in function is
not seen at kappaORs at neighboring excitatory synapses, suggesting distinct time
courses and mechanisms of regulation of different subsets of kappaORs. We also
provide evidence that constitutive activity of kappaORs governs the prolonged
reinstatement to cocaine-seeking observed after cold water swim stress. Together,
our studies indicate that stress-induced constitutive activation is a novel
mechanism of kappaOR regulation that plays a critical role in reinstatement of
drug seeking.
PMID- 28402254
TI - Vegetables and fruit, as a source of bioactive substances, and impact on memory
and cognitive function of elderly.
AB - The phenomenon of population aging is not only associated with an increase in the
number and proportion of older people in society, but also with an increase in
the incidence of cognitive impairment. This can impair the functioning of the
elderly in everyday life, work and social life participation and impair their
quality of life. Hence, it is important to identify the protective factors.
Neurodegenerative changes are closely linked to inflammatory processes and
oxidative stress. Diet is of great importance, with particular attention being
paid to the adequate intake of fruits and vegetables, due to their proven health
benefits. This may be correlated to the protective effect of the bioactive
substances that are present in fruits and vegetables, in particular flavonoids
and carotenoids. The elderly who consume 5 servings a day of fruits and
vegetables have a higher antioxidant capacity of blood serum, while the risk of
chronic diseases, including neurodegenerative and mortality rates are lower. The
analysis included the results of 16 published epidemiological studies, including
people aged 65+. Their results are discussed in 4 fields of the effects on
cognitive function (1) fruit and vegetable intake; (2) flavonoids intake; (3)
carotenoid nutritional status; (4) mechanism of action of plant bioactive
substances. It has been found that the positive effects of consumption of fruits
and vegetables may be associated with cognitive functions in the three possible
areas, ie.: (1) improvement in cognitive testing; (2) delaying or preventing age
related deterioration of cognitive decline; (3) reducing the risk of
neurodegenerative diseases.
PMID- 28402255
TI - Chemotherapy and plasma adipokines level in patients with colorectal cancer.
AB - Adipokines are molecules produced and secreted by adipose tissue and are linked
to multiple malignancies. Adipokines can suppress or promote particular cell
behaviors in different types of cancer. The aim of this study was to investigate
the impact of chemotherapy on select adipokines in patients with colorectal
cancer (CRC). Blood samples were collected from 42 patients with pathologically
documented advanced CRC, who required palliative chemotherapy. Leptin,
adiponectin, resistin and visfatin levels were measured by ELISA before and 3
months after the administration of chemotherapy. Among the 42 patients evaluated,
18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8
patients experienced disease progression (PD). We found that 5-fluorouracil-based
chemotherapy regimens significantly increased plasma levels of leptin and
adiponectin and decreased plasma levels of resistin and visfatin in PR and SD
patients, whereas the plasma levels of these molecules were not affected in PD
patients. Furthermore, the mean plasma levels of leptin were significantly lower,
and the mean plasma levels of resistin and visfatin were significantly greater in
patients with PD compared with PR and SD both before and after chemotherapy
treatment. We conclude that palliative chemotherapy in CRC patients, in addition
to providing clinical benefits, positively affects cytokine production and
secretion in PR and SD patients. Specifically, we found that palliative
chemotherapy increased plasma levels of the anti-inflammatory adipokine
adiponectin and decreased the plasma levels of visfatin and resistin, molecules
known to promote angiogenesis and cancer cell proliferation in PR and SD
patients. Moreover, the baseline values of leptin, visfatin and resistin might
serve as prognostic indicators of a poor response to chemotherapy.
PMID- 28402256
TI - A potential anti-tumor effect of leukotriene C4 through the induction of 15
hydroxyprostaglandin dehydrogenase expression in colon cancer cells.
AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths
worldwide. Cyclooxygenase-2, which plays a key role in the biosynthesis of
prostaglandin E2 (PGE2), is often up-regulated in CRC and in other types of
cancer. PGE2 induces angiogenesis and tumor cell survival, proliferation and
migration. The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH)
is a key enzyme in PGE2 catabolism, converting it into its inactive metabolite 15
keto-PGE2, and is often down-regulated in cancer. Interestingly, CRC patients
expressing high levels of the cysteinyl leukotriene 2 (CysLT2) receptor have a
good prognosis; therefore, we investigated a potential link between CysLT2
signaling and the tumor suppressor 15-PGDH in colon cancer cells.We observed a
significant up-regulation of 15-PGDH after treatment with LTC4, a CysLT2 ligand,
in colon cancer cells at both the mRNA and protein levels, which could be reduced
by a CysLT2 antagonist or a JNK inhibitor. LTC4 induced 15-PGDH promoter activity
via JNK/AP-1 phosphorylation. Furthermore, we also observed that LTC4, via the
CysLT2/JNK signaling pathway, increased the expression of the differentiation
markers sucrase-isomaltase and mucin-2 in colon cancer cells and that down
regulation of 15-PGDH totally abolished the observed increase in these markers.In
conclusion, the restoration of 15-PGDH expression through CysLT2 signaling
promotes the differentiation of colon cancer cells, indicating an anti-tumor
effect of CysLT2 signaling.
PMID- 28402258
TI - CD200Fc reduces LPS-induced IL-1beta activation in human cervical cancer cells by
modulating TLR4-NF-kappaB and NLRP3 inflammasome pathway.
AB - Chronic inflammation plays an important role in tumorigenesis of cervical cancer.
CD200Fc, a CD200R1 agonist, has been found to have anti-inflammatory effects in
autoimmune diseases and neuro-degeneration. However, the anti-inflammatory effect
of CD200Fc on cervical cancer has not yet to be completely understood. This study
investigated the anti-inflammatory effects and mechanisms of CD200Fc in LPS
induced human SiHa cells and Caski cells. SiHa cells and Caski cells were
stimulated with 40 MUg/ml LPS under different concentrations of CD200Fc for 90
min or 12 hours. The mRNA and protein levels of pro-IL-1beta, cleaved-IL-1beta
and NLRP3, as well as the protein level of cleaved caspase-1, were significantly
increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not
change ASC and pro-caspase-1 expression. CD200Fc down-regulated protein
expression of cleaved caspase-1 and mRNA and protein expression of pro-IL-1beta,
cleaved-IL-1beta and NLRP3. In addition, the protein levels of TLR4, p-P65 and p
IkappaB, as well as the translocation of P65 to nucleus, were significantly
increased in LPS-induced SiHa cells and Caski cells. LPS stimulation did not
change t-P65 and t-IkappaB on protein levels, which were components of TLR-NF
kappaB pathway. CD200Fc down-regulated protein expression of TLR4, p-P65 and p
IkappaB and inhibited the translocation of P65 to nucleus in LPS-induced SiHa
cells and Caski cells. These results indicated that CD200Fc appeared to suppress
the inflammatory activity of TLR4-NF-kappaB and NLRP3 inflammasome pathway in LPS
induced SiHa cells and Caski cells. It provided novel mechanistic insights into
the potential therapeutic uses of CD200Fc for cervical cancer.
PMID- 28402257
TI - (DEAD)-box RNA helicase 3 modulates NF-kappaB signal pathway by controlling the
phosphorylation of PP2A-C subunit.
AB - Asp-Glu-Ala-Asp (DEAD)-box RNA helicase 3 (DDX3), an ATP-dependent RNA helicase,
is associated with RNA splicing, mRNA export, transcription, translation, and RNA
decay. Recent studies revealed that DDX3 participates in innate immune response
during virus infection by interacting with TBK1 and regulating the production of
IFN-beta. In our studies, we demonstrated that DDX3 regulated NF-kappaB signal
pathway. We found that DDX3 knockdown reduced the phosphorylation of p65 and IKK
beta and ultimately attenuated the production of inflammatory cytokines induced
by poly(I:C) or TNF-alpha stimulation. The regulatory effect of DDX3 on NF-kappaB
signal pathway was not affected by the loss of its ATPase or helicase activity.
We further identified PP2A C subunit (PP2A-C) as an interaction partner of DDX3
by co-immunoprecipitation and mass spectrum analysis. We confirmed that DDX3
formed the complex with PP2A-C/IKK-beta and regulated the interaction between IKK
beta and PP2A-C. Furthermore, we demonstrated that DDX3 modulated the activity of
PP2A by controlling the phosphorylation of PP2A-C, which might enable PP2A-C to
regulate NF-kappaB signal pathway by dephosphorylating IKK-beta. All these
findings suggested DDX3 plays multiple roles in modulating innate immune system.
PMID- 28402259
TI - The design of novel inhibitors for treating cancer by targeting CDC25B through
disruption of CDC25B-CDK2/Cyclin A interaction using computational approaches.
AB - Cell division cycle 25B is a key cell cycle regulator and widely considered as
potent clinical drug target for cancers. This research focused on identifying
potential compounds in theory which are able to disrupt transient interactions
between CDC25B and its CDK2/Cyclin A substrate.By using the method of ZDOCK and
RDOCK, the most optimized 3D structure of CDK2/Cyclin A in complex with CDC25B
was constructed and validated using two methods: 1) the superimposition of
proteins; 2) analysis of the hydrogen bond distances of Arg 488(N1)-Asp 206(OD1),
Arg 492(NE)-Asp 206(OD1), Arg 492(N1)-Asp 206(OD2) and Tyr 497(NE)-Asp 210(OD1).
A series of new compounds was gained through searching the fragment database
derived from ZINC based on the known inhibitor-compound 7 by the means of
"replace fragment" technique. The compounds acquired via meeting the requirements
of the absorption, distribution, metabolism, and excretion (ADME) predictions.
Finally, 12 compounds with better binding affinity were identified. The comp#1,
as a representative, was selected to be synthesized and assayed for their CDC25B
inhibitory activities. The comp#1 exhibited mild inhibitory activities against
human CDC25B with IC50 values at about 39.02 MUM. Molecular Dynamic (MD)
simulation revealed that the new inhibitor-comp#1 had favorable conformations for
binding to CDC25B and disturbing the interactions between CDC25B and CDK2/Cyclin
A.
PMID- 28402260
TI - DNA plasmid vaccine carrying Chlamydia trachomatis (Ct) major outer membrane and
human papillomavirus 16L2 proteins for anti-Ct infection.
AB - Chlamydia trachomatis (Ct) is one of the most frequently encountered sexual
infection all over the world, yielding tremendous reproductive problems (e.g.
infertility and ectopic pregnancy) in the women. This work described the design
of a plasmid vaccine that protect mice from Ct infection, and reduce productive
tract damage by generating effective antibody and cytotoxic T cell immunity. The
vaccine, s was composed of MOMP multi-epitope and HPV16L2 genes carried in pcDNA
plasmid (i.e. pcDNA3.1/MOMP/HPV16L). In transfection, the vaccine expressed the
chimeric genes (i.e. MOMP and HPV16L2), as demonstrated via western blot, RT-PCR
and fluorescence imaging. In vitro, the vaccine transfected COS-7 cells and
expressed the proteins corresponding to the genes carried in the vaccine. Through
intramuscular immunization in BALB/c mice, the vaccine induced higher levels of
anti-Ct IgG titer, anti-HPV16L2 IgG titer in serum and IgA titer in local mucosal
secretions, compared to plasmid vaccines that carry only Ct MOMP multi-epitope or
HPV16L2 chimeric component only. In mice intravaginally challenged with Ct, the
vaccines pcDNA3.1/MOMP/HPV16L2 generated a higher level of genital protection
compared to other vaccine formulations. Additionally, histochemical staining
indicated that pcDNA3.1/MOMP/HPV16L2 eliminated mouse genital tract tissue
pathologies induced by Ct infection. This work demonstrated that
pcDNA/MOMP/HPV16L2 vaccine can protect against Ct infection by regulating
antibody production, cytotoxic T cell killing functions and reducing pathological
damage in mice genital tract. This work can potentially offer us a new vaccine
platform against Ct infection.
PMID- 28402261
TI - Association of CKIP-1 P21A polymorphism with risk of chronic heart failure in a
Chinese population.
AB - Pathological cardiac hypertrophy is an independent risk factor for chronic heart
failure. Casein kinase-2 interacting protein-1 (CKIP-1) can inhibit pathological
cardiac hypertrophy. Therefore, we investigated whether CKIP-1 nonsynonymous
polymorphism rs2306235 (Pro21Ala) contributes to risk and prognosis of chronic
heart failure in a Chinese population.A total of 923 adult patients with chronic
heart failure and 1020 age- and gender-matched healthy controls were recruited.
CKIP-1 rs2306235 polymorphism was genotyped using PCR-restriction fragment length
polymorphism. Additional follow-up data for 140 chronic heart failure patients
was evaluated. The rs2306235 G allele was associated with an increased risk of
chronic heart failure (OR = 1.38, 95% CI = 1.09-1.75, p = 0.007), especially in
patients with hypertension (OR = 1.45, 95% CI = 1.09-1.75, p = 0.006) and
coronary heart disease (OR = 1.41, 95% CI = 1.09-1.83, p = 0.010) after
adjustment for multiple cardiovascular risk factors. However, rs2306235
polymorphism was not associated with cardiovascular mortality in chronic heart
failure (p = 0.875). CKIP-1 rs2306235 polymorphism may be a risk factor for
chronic heart failure in a Chinese Han population.
PMID- 28402262
TI - Roles of differential expression of microRNA-21-3p and microRNA-433 in FSH
regulation in rat anterior pituitary cells.
AB - Follicle-stimulating hormone (FSH) secreted by adenohypophyseal cells plays an
important role in the regulation of reproduction, but whether microRNAs (miRNAs)
regulate the secretion of FSH remains unclear. In the present study, we predicted
and screened miRNAs that might act on the follicle-stimulating hormone beta
subunit (FSHb) gene of rats using the TargetScan program and luciferase reporter
assays, and the results identified two miRNAs, miR-21-3p and miR-433. We then
transfected these miRNAs into rat anterior adenohypophyseal cells and assessed
the FSHb expression levels in and FSH secretion by the transfected cells through
quantitative PCR and ELISA. The results showed that both miR-21-3p and miR-433
down-regulated the expression levels of FSHb and resulted in the decrease of the
secretion of FSH compared with the control group, and treatment with miR-21-3p
and miR-433 inhibitors up-regulated the expression levels of FSHb and resulted in
the increase of the secretion of FSH. Taken together, our results indicate that
miR-21-3p and miR-433 can down-regulate the expression of FSHb by directly
targeting the FSHb 3'UTR in rat primary pituitary cells. Our findings provide
evidence that miRNAs can regulate FSHb expression and further affect the
secretion of FSH and might contribute to the use of miRNAs for the regulation of
animal reproduction.
PMID- 28402263
TI - Post-pulmonary metastasectomy prognosis after curative resection for colorectal
cancer.
AB - PURPOSE: We aimed to compare disease-free survival after pulmonary metastasectomy
to that after hepatic metastasectomy, and to identify prognostic factors after
pulmonary metastasectomy. RESULTS: Between 2005 and 2015, 129 patients underwent
resection of isolated metachronous lung metastases from colorectal cancer. Three
year DFS after pulmonary metastasectomy was similar to that after hepatic
metastasectomy (50.7% vs. 45.5%, respectively; p=0.58). Rectal cancer (hazard
ratio [HR]: 2.04, 95% confidence interval [CI]: 1.09-3.79; p=0.03) and >=2
metastases (HR: 2.17, 95% CI: 1.28-3.68; p=0.004) were independent adverse risk
factors associated with disease-free survival after pulmonary metastasectomy on
multivariate analysis. Three-year DFS for colon vs. rectal cancer patients was
72.5% vs. 42.6%, respectively (p=0.04). The number of lung metastases was an
independent risk factor for DFS after pulmonary metastasectomy in rectal cancer
patients. PATIENTS AND METHODS: Patients who underwent lung metastasectomy after
curative resection of colorectal cancers were investigated. Disease-free survival
(DFS) after pulmonary metastasectomy was compared to that after hepatic
metastasectomy, which has a relatively well-known prognosis. Multivariate Cox
proportional hazards analysis was performed to identify clinical variables
predictive of survival after pulmonary metastasectomy. CONCLUSIONS: Disease-free
survival rates after resection of lung vs. liver metastases arising from
colorectal cancers are similar. However, lung metastases specifically from rectal
cancers produce poorer DFS rates. Primary tumor location must be considered for
pulmonary metastasis treatment and follow-up in colorectal cancer patients.
PMID- 28402264
TI - FHL2 interacts with iASPP and impacts the biological functions of leukemia cells.
AB - iASPP is an inhibitory member of apoptosis-stimulating proteins of p53 (ASPP)
family, which inhibits p53-dependent apoptosis. iASPP was highly expressed in
acute leukemia, inhibited leukemia cells apoptosis and promoted leukemogenesis.
In order to clarify its mechanism, a yeast two-hybrid screen was performed and
FHL2 was identified for the first time as one of the binding proteins of iASPP.
FHL2 was highly expressed in K562 and Kasumi-1 cells. FHL2 and iASPP interacted
with each other and co-localized in both nucleus and cytoplasm. Either FHL2 or
iASPP silenced could reduce cell proliferation, induce cell cycle arrest at G0/G1
phase, and increase cell apoptosis. Western blot analysis showed that the level
of p21 and p27 increased, CDK4, E2F1, Cyclin E and anti-apoptotic proteins Bcl-2
and Bcl-xL reduced. Interestingly, when FHL2 was knocked down, the protein
expression level of iASPP also decreased. Similarly, the expression of FHL2 would
reduce when iASPP was silenced. These results indicated that FHL2 might be a
novel potential target for acute myelocytic leukemia treatment.
PMID- 28402265
TI - Systematic comparison of biologically active foreign ions-codoped calcium
phosphate microparticles on osteogenic differentiation in rat osteoporotic and
normal mesenchymal stem cells.
AB - Osteoporosis is a disease characterized by structural deterioration of bone
tissue, leading to skeletal fragility with increased fracture risk. Calcium
phosphates (CaPs) are widely used in bone tissue engineering strategies as they
have similarities to bone apatite except for the absence of trace elements (TEs)
in the CaPs. Bioactive glasses (BGs) have also been used successfully in clinic
for craniomaxillofacial and dental applications during the last two decades due
to their excellent potential for bonding with bone and inducing osteoblastic
differentiation. In this study, we evaluated the osteogenic effects of the ionic
dissolution products of the quaternary Si-Sr-Zn-Mg-codoped CaP (TEs-CaP) or 45S5
Bioglass(r) (45S5 BG), both as mixtures and separately, on rat bone marrow
derived mesenchymal stem cells (rOMSCs & rMSCs) from osteoporotic and normal
animals, using an MTT test and Alizarin Red S staining. The materials enhanced
cell proliferation and osteogenic differentiation, especially the combination of
the BG and TEs-CaP. Analysis by quantitative PCR and ELISA indicated that the
expression of osteogenic-specific genes and proteins were elevated. These
investigations suggest that the TEs-CaP and 45S5 BG operate synergistically to
create an extracellular environment that promotes proliferation and terminal
osteogenic differentiation of both osteoporotic and normal rMSCs.
PMID- 28402266
TI - Expression signatures of HOX cluster genes in cervical cancer pathogenesis:
Impact of human papillomavirus type 16 oncoprotein E7.
AB - The Homeobox (HOX) genes encode important transcription factors showing
deregulated expression in several cancers. However, their role in cervical cancer
pathogenesis, remains largely unexplored. Herein, we studied their association
with Human Papillomavirus type 16 (HPV16) mediated cervical cancers. Our
previously published gene expression microarray data revealed a significant
alteration of 12 out of 39 HOX cluster members among cervical cancer cases, in
comparison to the histopathologically normal controls. Of these, we validated
seven (HOXA10, HOXA13, HOXB13, HOXC8, HOXC9, HOXC11 and HOXD10) by quantitative
real-time PCR. We identified decreased HOXA10 expression as opposed to the
increased expression of the rest. Such decrease was independent of the
integration status of HPV16 genome, but correlated negatively with E7 expression
in clinical samples, that was confirmed in vitro. HOXA10 and HOXB13 revealed
association with Epithelial-Mesenchymal Transition (EMT). While HOXA10 expression
correlated positively with E-Cadherin and negatively with Vimentin expression,
HOXB13 showed the reverse trend. Chromatin immunoprecipitation study in vitro
revealed the ability of E7 to increase HOX gene expression by epigenetic
regulation, affecting the H3K4me3 and H3K27me3 status of their promoters,
resulting from a loss of PRC2-LSD1 complex activity. Thus, besides identifying
the deregulated expression of HOX cluster members in HPV16 positive cervical
cancer and their association with EMT, our study highlighted the mechanism of
HPV16 E7-mediated epigenetic regulation of HOX genes in such cancers, potentially
serving as bedrock for functional studies in the future.
PMID- 28402267
TI - Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude
mice after irradiation with sub-threshold focused ultrasound for tumor ablation.
AB - We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors
after irradiation with sub-threshold focused ultrasound (FUS) ablation in
pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were
divided into three groups: Group A received sham irradiation, Group B received a
moderate-acoustic energy dose (sub-threshold), and Group C received a high
acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and
dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and
after irradiation. After irradiation, tumor growth was inhibited in Group B, and
the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In
Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of
contrast agent into and out of tumors before irradiation. After irradiation, CEUS
revealed contrast agent perfusion only at the tumor periphery and irregular, un
perfused volumes of contrast agent within the tumors. DCE-US perfusion
parameters, including peak intensity (PI) and area under the curve (AUC), had
decreased 24 hours after irradiation. PI and AUC were increased 48 hours and
2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours
after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS
is thus an effective method for early evaluation after irradiation with sub
threshold FUS.
PMID- 28402268
TI - Suppression of radiation-induced migration of non-small cell lung cancer through
inhibition of Nrf2-Notch Axis.
AB - Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor that is
associated with tumor growth and resistance to radiation. The canonical Notch
signaling pathway is also crucial for maintaining non-small cell lung cancer
(NSCLC). Aberrant Nrf2 and Notch signaling has repeatedly been showed to
facilitate metastasis of NSCLC. Here, we show that radiation induce Nrf2 and
Notch1 expression in NSCLC. Knockdown of Nrf2 enhanced radiosensitivity of NSCLC
and reduced epithelial-to-mesenchymal transition. Importantly, we found that
knockdown of Nrf2 dramatically decreased radiation-induced NSCLC invasion and
significantly increased E-cadherin, but reduced N-cadherin and matrix
metalloproteinase (MMP)-2/9 expression. We found that Notch1 knockdown also
upregulated E-cadherin and suppressed N-cadherin expression. Nrf2 contributes to
NSCLC cell metastatic properties and this inhibition correlated with reduced
Notch1 expression. These results establish that Nrf2 and Notch1 downregulation
synergistically inhibit radiation-induced migratory and invasive properties of
NSCLC cells.
PMID- 28402269
TI - Long term storage in liquid nitrogen leads to only minor phenotypic and gene
expression changes in the mammary carcinoma model cell line BT474.
AB - BACKGROUND/AIM: Cancer cell lines are indispensible surrogate models in cancer
research, as they can be used off-the-shelf, expanded to the desired extent,
easily modified and exchanged between research groups for affirmation,
reproduction or follow-up experiments.As malignant cells are prone to genomic
instability, phenotypical changes may occur after certain passages in culture.
Thus, cell lines have to be regularly authenticated to ensure data quality. In
between experiments these cell lines are often stored in liquid nitrogen for
extended time periods.Although freezing of cells is a necessary evil, little
research is performed on how long-term storage affects cancer cell lines.
Therefore, this study investigated the effects of a 28-year long liquid nitrogen
storage period on BT474 cells with regard to phenotypical changes, differences in
cell-surface receptor expression as well as cytokine and gene expressional
variations. METHODS: Two batches of BT474 cells, one frozen in 1986, the other
directly purchased from ATCC were investigated by light microscopy, cell growth
analysis, flow cytometry and cytokine as well as whole-transcriptome expression
profiling. RESULTS: The cell lines were morphologically indifferent and showed
similar growth rates and similar cell-surface receptor expression. Transcriptome
analysis revealed significant differences in only 26 of 40,716 investigated
RefSeq transcripts with 4 of them being up-regulated and 22 down-regulated.
CONCLUSION: This study demonstrates that even after very long periods of storage
in liquid nitrogen, cancer cell lines display only minimal changes in their gene
expression profiles. However, also such minor changes should be carefully
assessed before continuation of experiments, especially if phenotypic alterations
can be additionally observed.
PMID- 28402270
TI - AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK
signaling.
AB - BACKGROUND: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be
significantly induced in the cells of various cancers such as breast cancer.
However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer
remain unclear. In the present study, we demonstrated the potential role and
mechanism of AKR1B10 in the invasion and migration of breast cancer cells.
METHODS: The expression level of AKR1B10 in breast carcinoma, para-carcinoma and
cancer tissues were detected by immunohistochemical evaluation and real-time
polymerase chain reaction (RT-PCR), and the correlationships between AKR1B10
expression and clinicopathological features in breast cancer patients (n=131)
were investigated. AKR1B10 was ectopically expressed in MCF-7 cells or silenced
in BT-20 cells. The roles of AKR1B10 expression in the migration and invasion of
MCF-7 cells and BT-20 cells were explored by wound healing assay, transwell
migration assay and transwell matrigel invasion assay, and finally the activation
level of extracellular signal-regulated kinase 1/2 (EKR1/2) activation and the
expression level of matrix metalloproteinase-2 (MMP2) and vimentin in MCF-7 and
BT-20 cells were measured by western blot. RESULTS: We found that AKR1B10
expression was increased in malignant tissues, which was correlated positively
with tumor size, lymph node metastasis (p<0.05). MCF-7/AKR1B10 cells displayed a
higher ability of migration (43.57+/-1.04%) compared with MCF-7/vector cells
(29.12+/-1.34%) in wound healing assay, and the migrated cell number of MCF
7/AKR1B10 was more (418.43+/-9.62) than that of MCF-7/vector (222.43+/-17.75) in
transwell migration assay without matrigel. We furtherly confirmed MCF-7/AKR1B10
cells invaded faster compared with MCF-7/vector cells by transwell matrigel
invasion assay. Finally, we found AKR1B10 induced the migration and invasion of
MCF-7 and BT-20 cells by activating EKR signaling, which promoted the expressions
of MMP2 and vimentin. PD98059, a specific inhibitor of the activation of MEK,
blocked the migration and invasion by inhibiting the expression of MMP2 and
vimentin. CONCLUSIONS: AKR1B10 is overexpressed in breast cancer, and promotes
the migration and invasion of MCF-7 and BT-20 cells by activating ERK signaling
pathway.
PMID- 28402271
TI - Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and
cancer cells in glioblastoma: An in vitro boron neutron capture therapy study.
AB - The efficacy of boron neutron capture therapy depends on the selective delivery
of 10B to the target. Integrins alphavbeta3 are transmembrane receptors over
expressed in both glioblastoma cells and its neovasculature. In this study, a
novel approach to dual-target glioblastoma vasculature and tumor cells was
investigated. Liposomes (124 nm) were conjugated with a alphavbeta3 ligand,
cyclic arginine-glycine-aspartic acid-tyrosine-cysteine peptide (c(RGDyC)-LP) (1%
molar ratio) through thiol-maleimide coupling. Expression of alphavbeta3 in
glioblastoma cells (U87) and human umbilical vein endothelial cells (HUVEC),
representing tumor angiogenesis, was determined using Western Blotting with other
cells as references. The results showed that both U87 and HUVEC had stronger
expression of alphavbeta3 than other cell types, and the degree of cellular
uptake of c(RGDyC)-LP correlated with the alphavbeta3-expression levels of the
cells. In contrast, control liposomes without c(RGDyC) showed little cellular
uptake, regardless of cell type. In an in vitro boron neutron capture therapy
study, the c(RGDyC)-LP containing sodium borocaptate generated more rapid and
significant lethal effects to both U87 and HUVEC than the control liposomes and
drug solution. Interestingly, neutron irradiated U87 and HUVEC showed different
types of subsequent cell death. In conclusion, this study has demonstrated the
potential of a new dual-targeting strategy using c(RGDyC)-LP to improve boron
neutron capture therapy for glioblastoma.
PMID- 28402272
TI - Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO
sumoylation and NF-kappaB activity.
AB - Ginkgolic acids (GA), a group of alkyl phenols found in crude extracts of Ginkgo
biloba leaves, are known to have anticancer activity, but their mode of action is
not well understood. Our aim in this study was to investigate the anti-migratory
activity of seven GA against breast cancer cells and to determine the molecular
mechanism behind this activity. All seven GA and their mixture inhibited wound
healing in MCF-7 and MDA-MB 231 breast cancer cells. None of the compounds nor
the mixture showed cytotoxicity towards the two cell lines, if tested by the
resazurin assay. C13:0 inhibited NF-kappaB activity in the HEK Blue Null 1
reporter cell line. Furthermore, C13:0 inhibited degradation of nuclear factor of
kappa-light polypeptide gene enhancer in B-cells inhibitor alpha (IkappaBalpha).
Sumoylation assay revealed that GA inhibited sumoylation of NF-kappaB essential
modulator (NEMO). Molecular docking on SUMO-activating enzyme E1 showed that the
seven GA bound to the active adenylation site with high calculated affinities
ranging from -10.28 to -12.27 kcal/mol. Quantitative RT-PCR using C15:0, C13:0
and the mixture showed a significant down-regulation of urokinase plasminogen
activator (uPA), plasminogen activator inhibitor-1 (PAI-1), C-X-C chemokine
receptor type 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9). We conclude that
GA revealed considerable anti-migratory activity at non-cytotoxic concentrations,
indicating anti-metastatic activity with low toxicity. This effect can be
explained by the inhibition of NEMO sumoylation leading to inhibition of
IkappaBalpha degradation and consequently a reduction of NF-kappaB activity,
leading to the down-regulation of metastasis related genes including uPA, PAI-1,
CXCR4, and MMP-9.
PMID- 28402273
TI - Serum IL-33 level is a predictor of progression-free survival after chemotherapy.
AB - This study aimed to evaluate the association between of serum IL-33 (sIL-33)
level in gastric cancer (GC) patients and progression-free survival (PFS). A
total of 62 patients with advanced GC and 32 healthy subjects were enrolled. sIL
33 level was detected in pre-chemotherapy patients, post-chemotherapy patients
and healthy subjects, respectively. sIL-33 levels were 131.9 (95% CI 105.9-184.9)
pg/mL, 95.1 (95% CI 70.8-140.2) pg/mL and 95.7 (95% CI 73.3-114.3) pg/mL in pre
chemotherapy patients, post-chemotherapy patients and controls, respectively. The
sIL-33 level in pre-chemotherapy patients was significantly higher than that in
both post-chemotherapy patients and controls (P < 0.001 and P < 0.001,
respectively). There was no statistically significant difference between the sIL
33 levels in post-chemotherapy patients and controls (P > 0.05). PFS in patients
with the decline extent > 30.1% (median PFS not reached) was statistically
significant longer than that (median PFS 7 months, 95% CI 1.569 - 12.431) in
patients with the decline extent <= 30.1% (P = 0.003). The decline extent of sIL
33 level (> 30.1%) was associated with longer PFS (P = 0.006). Distant metastasis
was associated with the decline extent of sIL-33 level (P = 0.034). The decline
extent of sIL-33 after chemoresistance could be regarded as a predictor of the
PFS of GC patients.
PMID- 28402274
TI - Magnesium isoglycyrrhizinate shows hepatoprotective effects in a cyclophosphamide
induced model of hepatic injury.
AB - The purpose of the current study was to investigate the effect of Magnesium
Isoglycyrrhizinate (GM) on cyclophosphamide (CP)-induced hepatic injury in vivo
and in vitro. The results demonstrated that GM exerted a protective effect on CP
induced acute liver injury, as evidenced by the alleviations of hepatic
pathological damage and serum transaminase activities. Meantime, GM attenuated
serum and HepG2 cell supernatant levels of TNF-alpha, IL-6, IL-1beta, SOD and
MDA. Western blot results presented that GM down-regulated the expressions of the
microtubule associated protein 1A/1B-light chain 3 (LC3), Lysosome associated
membrane protein-1 (LAMP-1), p-phosphatidylinositol 3-kinase (PI3K), p-protein
Kinase B(Akt), p-mechanistic target of rapamycin(mTOR), p-ribosomal protein S6
kinase 70 kDa (p70S6K), p-4E binding protein 1(4EBP1), p- inhibitor of NF
kappaB(IkappaB)alpha and p-nuclear factor kappa B(NF-kappaB)p65 in CP-stimulated
hepatic tissue and HepG2 cells. Taken together, our results suggested that GM
showed beneficial effect on CP-induced liver injury through NF-kappaB-mediated
inflammation and PI3K/Akt/mTOR/p70S6K/4EBP1 axis-mediated autophagy in vivo and
in vitro.
PMID- 28402275
TI - The value of FATS expression in predicting sensitivity to radiotherapy in breast
cancer.
AB - PURPOSE: The fragile-site associated tumor suppressor (FATS) is a newly
identified tumor suppressor involved in radiation-induced tumorigenesis. The
purpose of this study was to characterize FATS expression in breast cancers about
radiotherapy benefit, patient characteristics, and prognosis. RESULTS: The
expression of FATS mRNA was silent or downregulated in 95.2% of breast cancer
samples compared with paired normal controls (P < .0001). Negative status of FATS
was correlated with higher nuclear grade (P = .01) and shorter disease-free
survival (DFS) of breast cancer (P = .036). In a multivariate analysis, FATS
expression showed favorable prognostic value for DFS (odds ratio, 0.532; 95%
confidence interval, 0.299 to 0.947; (P = .032). Furthermore, improved survival
time was seen in FATS-positive patients receiving radiotherapy (P = .006). The
results of multivariate analysis revealed independent prognostic value of FATS
expression in predicting longer DFS (odds ratio, 0.377; 95% confidence interval,
0.176 to 0.809; P = 0.012) for patients receiving adjuvant radiotherapy. In
support of this, reduction of FATS expression in breast cancer cell lines, FATS
positive group significantly sensitized than Knock-down of FATS group. MATERIALS
AND METHODS: Tissue samples from 156 breast cancer patients and 42 controls in
tumor bank were studied. FATS gene expression was evaluated using quantitative
reverse transcription polymerase chain reaction (qRT-PCR). FATS function was
examined in breast cancer cell lines using siRNA knock-downs and colony forming
assays after irradiation. CONCLUSIONS: FATS status is a biomarker in breast
cancer to identify individuals likely to benefit from radiotherapy.
PMID- 28402276
TI - Cell cycle protein Bora serves as a novel poor prognostic factor in multiple
adenocarcinomas.
AB - Cell cycle protein Bora has been identified to integrate the functions of three
major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora
A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic
instability. However, the clinical relevance of Bora in cancer remains unclear.
In this study, we examined the expression of Bora and its association with
clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77)
adenocarcinomas. We found that Bora was overexpressed in primary breast cancer
tissues compared to paired non-cancerous tissues. Bora overexpression was
observed at a higher proportion in triple-negative breast cancer (TNBC, 77.63%)
compared with non-TNBC subtypes (42.76%, P < 0.0001). Kaplan-Meier survival
analysis indicated that Bora overexpression was associated with unfavourable
overall survival (OS, P < 0.0001) and disease-free survival (DFS, P = 0.007) in
breast cancer. In addition, Bora subclassified patients with distinct clinical
outcomes in both stages (II/III) and subtypes (HR+, HER2+) of breast cancer.
Consistently, Bora was associated with adverse prognosis in lung (P = 0.005 for
OS and DFS P = 0.001 for DFS) and gastric adenocarcinomas (P < 0.0001 for OS, and
P < 0.0001 for DFS). Moreover, Bora was positively correlated with proliferation
index Ki67 in breast and gastric cancer (P < 0.001, P = 0.005, respectively).
Multivariate analyses further revealed that Bora was an independent prognostic
parameter for OS and DFS in all three types of adenocarcinomas. In conclusion,
our findings demonstrated that Bora was overexpressed and served as an
independent biomarker for poor prognosis in multiple adenocarcinomas.
PMID- 28402277
TI - The influence of tumor necrosis factor-alpha on the tumorigenic Wnt-signaling
pathway in human mammary tissue from obese women.
AB - Epidemiological studies have convincingly suggested that obesity is an important
risk factor for postmenopausal breast cancer, but the mechanisms responsible for
this relationship are still not fully understood. We hypothesize that obesity
creates a low-grade inflammatory microenvironment, which stimulates Wnt-signaling
and thereby promotes the development of breast cancer. To test this hypothesis,
we evaluated the correlations between expression of multiple inflammatory
cytokines and Wnt pathway downstream genes in mammary tissues from women (age >=
50) undergoing reduction mammoplasty. Moreover, we specifically examined the role
of tumor necrosis factor-alpha (TNF-alpha), an important proinflammatory cytokine
associated with obesity and a possible modulator of the Wnt pathway. The
regulatory effects of TNF-alpha on Wnt pathway targets were measured in an ex
vivo culture of breast tissue treated with anti-TNF-alpha antibody or TNF-alpha
recombinant protein. We found that BMI was positively associated with the
secretion of inflammatory cytokines IL-1beta, IL-6 and TNF-alpha, all of which
were negatively correlated with the expression of SFRP1. The transcriptional
expression of Wnt-signaling targets, AXIN2 and CYCLIN D1, were higher in mammary
tissue from women with BMI >= 30 compared to those with BMI < 30. Our ex vivo
work confirmed that TNF-alpha is causally linked to the up-regulation of active
beta-CATENIN, a key component in the Wnt pathway, and several Wnt-signaling
target genes (i.e. CYCLIN D1, AXIN2, P53 and COX-2). Collectively, these findings
indicate that obesity-driven inflammation elevates Wnt-signaling in mammary
tissue and thereby creates a microenvironment conducive to the development of
breast cancer.
PMID- 28402278
TI - Correlated high expression of FXR and Sp1 in cancer cells confers a poor
prognosis for pancreatic cancer: A study based on TCGA and tissue microarray.
AB - Bile acids (BAs) was critical in the initiation and progression of various
tumors. However, their prognostic significance in pancreatic cancer was still
illusive. In the present study, the expression and biological significance of
FXR, a major receptor of BAs, in the lethal disease were evaluated in mRNA and
protein levels. We found that FXR protein was elevated in the cancerous tissues,
which was significantly higher than the adjacent tissues (p < 0.05). Meanwhile,
our data showed that FXR was positively correlated with primary tumor location (p
= 0.04) and poor survival (p = 0.002). Finally, COX regression model indicated
that FXR protein was an independent prognostic factor (p = 0.01; HR = 2.15; 95%
CI 1.27-3.63). Consistently, we also found a significant difference of FXR
expression between the high and low groups in mRNA level (p < 0.001), and that
high FXR expression confers a poor prognosis (p < 0.001). More importantly, the
correlation assay showed that FXR was positively correlated Sp1 in both protein
(r = 0.351, p = 0.008) and mRNA levels (r = 0.263, p < 0.01), with the
simultaneously high expression indicated the worst prognosis on protein (p <
0.001) and mRNA levels (p < 0.001). Additionally, we also showed that FXR was
elevated in the pancreatic cancer cells responsible for proliferation and
migration. Overall, the data suggested co-high expression of the two factors was
an independent prognostic factor (p < 0.001; HR = 3.27; 95% CI 1.86-5.76). Based
on these data, we proposed a model to link FXR to Sp1, which included triggered
FXR, p38/MAPK and/or PI3K/AKT signaling and phosphorylated Sp1, to illustrate the
potential crosstalk between the two factors.
PMID- 28402279
TI - Intensity modulated radiotherapy with fixed collimator jaws for locoregional left
sided breast cancer irradiation.
AB - The purpose of this study is to evaluate the intensity modulated radiotherapy
(IMRT) with the fixed collimator jaws technique (FJT) for the left breast and
regional lymph node. The targeted breast tissue and the lymph nodes, and the
normal tissues were contoured for 16 left-sided breast cancer patients previously
treated with radiotherapy after lumpectomy. For each patient, treatment plans
using different planning techniques, i.e., volumetric modulated arc therapy
(VMAT), tangential IMRT (tangential-IMRT), and IMRT with FJT (FJT-IMRT) were
developed for dosimetric comparisons. A dose of 50Gy was prescribed to the
planning target volume. The dose-volume histograms were generated, and the paired
t-test was used to analyze the dose differences. FJT-IMRT had similar mean heart
volume receiving 30Gy (V30 Gy) with tangential-IMRT (1.5% and 1.6%, p = 0.41),
but inferior to the VMAT (0.8%, p < 0.001). In the average heart mean dose
comparison, FJT-IMRT had the lowest value, and it was 0.6Gy lower than that for
the VMAT plans (p < 0.01). A significant dose increase in the contralateral
breast and lung was observed in VMAT plans. Compared with tangential-IMRT and
VMAT plans, FJT-IMRT reduced the mean dose of thyroid, humeral head and cervical
esophageal by 47.6% (p < 0.01) and 45.7% (p < 0.01), 74.3% (p =< 0.01) and 73% (p
=< 0.01), and 26.7% (p =< 0.01) and 29.2% (p =< 0.01). In conclusion, compared
with tangential-IMRT and VMAT, FJT-IMRT plan has the lowest thyroid, humeral head
and cervical esophageal mean dose and it can be a reasonable treatment option for
a certain subgroup of patients, such as young left-breast cancer patients and/or
patients with previous thyroid disease.
PMID- 28402281
TI - New species of Aberrapex Jensen, 2001 (Cestoda: Lecanicephalidea) from eagle rays
of the genus Myliobatis Cuvier (Myliobatiformes: Myliobatidae) from off
Argentina.
AB - Three new species of Aberrapex Jensen, 2001 (Cestoda: Lecanicephalidea) have been
collected from species of Myliobatis Cuvier along the coast of Argentina.
Aberrapex ludmilae sp. n. parasitises M. goodei Garman in the San Matias Gulf.
This species is unique in a combination of features including the shape and
extent of the uterus, scolex size, testis distribution, and by lacking an
external seminal vesicle and postovarian vitelline follicles. Aberrapex
sanmartini sp. n. from M. goodei in San Blas Bay and A. vitalemuttiorum sp. n.
from M. ridens Ruocco, Lucifora, Diaz de Astarloa, Mabragana et Delpiani in
coastal waters off Buenos Aires Province, are distinguished from all other
congeners by the microthrix pattern on the scolex surface, uterus shape and
extension, position of the connection of the uterine duct to the uterus, presence
and extension of an external seminal vesicle, and its overall size and number of
proglottids. The specimens of M. goodei and M. ridens show locally distinct
cestode faunas, which are correlated with well-defined biogeographic regions.
Some of these areas correspond with mating and nursery zones for species of
Myliobatis.
PMID- 28402282
TI - Two new species of nematode parasites, Cucullanus epinepheli sp. n.
(Cucullanidae) and Procamallanus (Spirocamallanus) sinespinis sp. n.
(Camallanidae), from marine serranid and haemulid fishes off New Caledonia.
AB - Based on light and scanning electron microscopical studies, two new species of
parasitic nematodes are described from marine perciform fishes off New Caledonia:
Cucullanus epinepheli sp. n. (Cucullanidae) from the intestine of the
brownspotted grouper Epinephelus chlorostigma (Valenciennes) (Serranidae) and
Procamallanus (Spirocamallanus) sinespinis sp. n. from the intestine of the
silver grunt Pomadasys argenteus (Forsskal) (Haemulidae). Cucullanus epinepheli
sp. n. differs from its congeners mainly in possessing a unique structure of the
anterior, elevated cloacal lip with a large posterior outgrowth covering the
cloacal aperture and in the presence of cervical alae and two small preanal
papillae on the median dome-shaped precloacal elevation. This is the second known
nominal species of this genus parasitising fishes of the family Serranidae and
the second representative of Cucullanus Muller, 1777 recorded from fishes in New
Caledonian waters. Procamallanus (Spirocamallanus) sinespinis sp. n. is mainly
characterised by 10-12 spiral ridges in the buccal capsule, the presence of wide
caudal alae, three pairs of pedunculate preanal papillae, two unequally long
spicules (465-525 um and 218-231 um) and by the tail tip with a knob-like
structure in the male, and the broad, rounded tail with a terminal digit-like
protrusion without cuticular spikes in the female. This is the fifth nominal
species of the subgenus Spirocamallanus Olsen, 1952 reported from fishes in New
Caledonian waters.
PMID- 28402280
TI - Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal
inflammation and esophageal carcinoma.
AB - Esophagitis and Barrett's esophagus are linked to esophageal squamous cell
carcinoma and adenocarcinoma, respectively. However, the underlying mechanisms
are still unclear. This study analyzed the expression levels of and correlation
between PLCE1 and PRKCA in human esophagitis, carcinogen NMBA-induced rat
esophagus, PLCE1 genetic deficient mouse esophageal epithelial tissues and human
esophageal cancer cell line, integrated with Online oncology data sets. We found
that the expression levels of both PLCE1 and PRKCA were significantly elevated in
human esophagitis, esophageal squamous cell carcinoma, Barrett's esophagus,
esophageal adenocarcinoma and in NMBA-treated rat esophageal epithelia. However,
PRKCA and cytokines were significantly downregulated in PLCE1-deficient mouse
esophageal epithelia, and knockdown of PLCE1 in human esophageal cancer cells led
to reduction of PRKCA and cytokines. Finally, high expression of both PLCE1 and
PRKCA is significantly associated with poor outcomes of the patients with
esophageal cancers. In conclusion, this study defined the initiation and
progression of esophageal inflammation and malignant transformation, in which the
positive correlation of PLCE1 and PRKCA exhibits critical clinical significance.
PMID- 28402283
TI - Some nematodes, including two new species, from freshwater fishes in the Sudan
and Ethiopia.
AB - Fourteen species (twelve adult and two larval) of nematodes belonging to the
Ascaridoidea, Camallanoidea, Cosmocercoidea, Habronematoidea, Oxyuroidea,
Seuratoidea and Trichinelloidea were collected from fishes in the Sudan (River
Nile and Atbara Dam Lake), whereas only four species (one adult and three larval)
of the Ascaridoidea, Camallanoidea, Dioctophymatoidea and Trichinelloideafrom
fishes in Ethiopia (Lake Tana). The Sudanese material also contained two
previously unknown species, Cucullanus mormyri sp. n. from Mormyrus caschive
Linnaeus (type host), Mormyrus sp. and Marcusenius cyprinoides (Linnaeus) (all
Mormyridae), and Procamallanus (Spirocamallanus) pseudospiralis sp. n. from
Synodontis schall (Bloch et Schneider) (type host), S. frontosus Vaillant and S.
nigrita Valenciennes (all Mochokidae), which are described based on light and
scanning electron microscopical studies. Cucullanus baylisi Campana-Rouget, 1961,
a little-known parasite of Synodontis spp., is redescribed in detail. A key to
Procamallanus (Spirocamallanus) spp. from African inland fishes is provided.
Falcaustra guiersi Vassiliades, 1973 is considered a junior synonym of F.
hexapapillata (Khalil, 1962). The findings represent several new host and
geographical records. Cucullanus baylisi Lakshmi, 2000 (= a homonym to C. baylisi
Campana-Rouget, 1961) is re-named as C. dubius nom. n. and is considered a
species inquirenda.
PMID- 28402284
TI - Three new genera of rhinebothriidean cestodes from stingrays in Southeast Asia.
AB - Three genera of rhinebothriideans, previously referred to as New genus 1, New
genus 2 and New genus 4, are erected in the the Anthocephaliidae. New genus 1 is
established as Divaricobothrium gen. n., with Divaricobothrium tribelum sp. n. as
its type species; Echeneibothrium trifidum Shipley et Hornell, 1906 is
transferred to the genus as Divaricobothrium trifidum (Shipley et Hornell, 1906)
comb. n. This genus is unique among rhinebothriidean genera in bearing bothridia
that are posteriorly deeply divided into two lobes with facial loculi but no
apical sucker, and a vagina that extends to near the anterior margin of the
proglottid. Its species parasitise Indo-Pacific members of the genera Brevitrygon
Last, Naylor et Manjaji-Matsumoto, Maculabatis Last, Naylor et Manjaji-Matsumoto
and Pateobatis Last, Naylor et Manjaji-Matsumoto. New genus 2 is established as
Barbeaucestus gen. n., with Barbeaucestus jockuschae sp. n. as its type species;
Barbeaucestus ralickiae sp. n. is also described. Anthobothrium sexorchidum
Williams, 1964 and Rhinebothrium shipleyi Southwell, 1912 are transferred to the
genus as Barbeaucestus sexorchidus (Williams, 1964) comb. n. and Barbeaucestus
shipleyi (Southwell, 1912) comb. n., respectively. This genus is unique among
rhinebothriidean genera in that its bothridia are substantially wider than long,
bear an apical sucker and at least one row of two or more facial loculi in their
anterior half. Its species parasitise the genera Neotrygon Castelnau and Taeniura
Muller et Henle. New genus 4 is established as Sungaicestus gen. n. with transfer
of Rhinebothrium kinabatanganensis Healy, 2006, as Sungaicestus kinabatanganensis
(Healy, 2006) comb. n., as its type species. Among the genera of its order, this
genus most closely resembles Rhinebothrium Linton, 1890, however, despite the
original description, the bothridia were found to bear, rather than lack, apical
suckers. This monotypic genus is known only from the freshwater stingray
Urogymnus polylepis (Muller et Henle). The familial diagnosis of the
Anthocephaliidae Ruhnke, Caira et Cox, 2015 is emended. The family now houses
five genera.
PMID- 28402285
TI - Doping of graphene induced by boron/silicon substrate.
AB - In this work, we show the doping of graphene most likely from heteroatoms induced
by the substrate using Raman spectra, x-ray photoelectron spectroscopy, energy
dispersive x-ray spectroscopy and ab initio molecular dynamics (MD) simulations.
The doping of graphene on a highly boron-doped silicon substrate was achieved by
an annealing at 400 K for about 3 h in an oven with air flow. With the same
annealing, only the Raman features similar to that from the pristine graphene
were observed in the freestanding graphene and the graphene on a typical Si/SiO2
wafer. Ab initio MD simulations were performed for defected graphene on boron
doped silicon substrate at several temperatures. All vacancy sites in the
graphene are occupied either with B atoms or Si atoms resulting in the mixed
boron-silicon doping of the graphene. The MD simulations validated the
experimetal finding of graphene doped behavior observed by Raman spectrum. The
electronic structure analysis indicated the p-type nature of doped graphene. The
observed doping by the possible incorporation of heteroatoms into the graphene,
simply only using 400 K annealing the boron-doped Si substrate, could provide a
new approach to synthesize doped graphene in a more economic way.
PMID- 28402287
TI - Regularization parameter selection for penalized-likelihood list-mode image
reconstruction in PET.
AB - Penalized likelihood (PL) reconstruction has demonstrated potential to improve
image quality of positron emission tomography (PET) over unregularized ordered
subsets expectation-maximization (OSEM) algorithm. However, selecting proper
regularization parameters in PL reconstruction has been challenging due to the
lack of ground truth and variation of penalty functions. Here we present a method
to choose regularization parameters using a cross-validation log-likelihood
(CVLL) function. This new method does not require any knowledge of the true image
and is directly applicable to list-mode PET data. We performed statistical
analysis of the mean and variance of the CVLL. The results show that the CVLL
provides an unbiased estimate of the log-likelihood function calculated using the
noise free data. The predicted variance can be used to verify the statistical
significance of the difference between CVLL values. The proposed method was
validated using simulation studies and also applied to real patient data. The
reconstructed images using optimum parameters selected by the proposed method
show good image quality visually.
PMID- 28402286
TI - Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant
chemotherapy.
AB - We measure tissue blood flow markers in breast tumors during neoadjuvant
chemotherapy and investigate their correlation to pathologic complete response in
a pilot longitudinal patient study (n = 4). Tumor blood flow is quantified
optically by diffuse correlation spectroscopy (DCS), and tissue optical
properties, blood oxygen saturation, and total hemoglobin concentration are
derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study
represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in
humans over the entire course of treatment; it therefore offers a first
correlation between DCS flow indices and pathologic complete response. The use of
absolute optical properties measured by DOSI facilitates significant improvement
of DCS blood flow calculation, which typically assumes optical properties based
on literature values. Additionally, the combination of the DCS blood flow index
and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen
metabolism. Pilot results from four patients suggest that lower blood flow in the
lesion-bearing breast is correlated with pathologic complete response. Both
absolute lesion blood flow and lesion flow relative to the contralateral breast
exhibit potential for characterization of pathological response. This initial
demonstration of the combined optical approach for chemotherapy monitoring
provides incentive for more comprehensive studies in the future and can help
power those investigations.
PMID- 28402288
TI - Efficient near-infrared light-emitting diodes based on liquid PbSe quantum dots.
AB - Recently, near-infrared light-emitting diodes (NIR LEDs) based on PbSe quantum
dots (QDs) have attracted considerable attention due to their facilely tunable
emission wavelength, as well as high quantum yield. However, the low external
quantum efficiency (EQE) of these LEDs has restricted their actual applications
because of the non-radiative recombination caused by the aggregation in the solid
state QD films. Therefore, we proposed in this work to employ the liquid-type
structure in NIR LEDs base on PbSe QDs, which exhibited the main advantages
relying on the fact that the liquid structure could prevent the active layer from
self-aggregation and improve the device stability. The emission intensity of
these NIR LEDs was optimized by tuning the concentration of PbSe QDs. Besides,
the radiation power of PbSe QD-based devices with different emission wavelengths
was analyzed under different biases, and the maximum EQE of NIR LEDs was
confirmed to be 5.3%. This result represents the highest record among the
reported NIR QD-LEDs, indicating this kind of liquid-type NIR LEDs is promising
for commercial applications.
PMID- 28402289
TI - A gas scintillator detector for 2D dose profile monitoring in pencil beam
scanning and pulsed beam proton radiotherapy treatments.
AB - In order to address dosimetry demands during proton therapy treatments utilizing
pencil beam scanning and/or pulsed beam accelerators, we have developed a xenon
filled gas scintillation detector (GSD) that can monitor delivered dose and 2D
beam centroid position pulse-by-pulse in real time, with high response linearity
up to high instantaneous dose rates. We present design considerations for the GSD
and results of beam tests carried out at operating proton therapy clinics. In
addition to demonstrating spatial resolution with sigma of a few hundred microns
in each transverse dimension and relative dose precision better than 1% over
large treatment areas, the test beam results also reveal the dependence of the
GSD dose normalization on dose rate, beam energy, and gas impurities. The results
demonstrate the promise of the GSD technology to provide an important addition to
dosimetry approaches for next-generation ion beam therapy.
PMID- 28402290
TI - Improved UV response of ZnO nanotubes by resonant coupling of anchored plasmonic
silver nanoparticles.
AB - In this study, plasmonic silver (Ag) nanoparticle-(NP) anchored ZnO nanorods
(NRs) and nanotube-(NT) based UV photodetectors are demonstrated. Here, Ag NPs
are synthesized and anchored by using a room-temperature photochemical method by
exposing the precursor solution in UV radiation. In order to achieve a stronger
surface plasmon resonance (SPR) and minimum agglomeration, the photochemical
method is optimized with a precursor concentration of 5 mmol, a UV intensity of
0.4 mW . cm-2, and an exposure time of 30 min. An asymmetry around 380 nm in the
absorption spectra of the NP solution indicates the presence of plasmonic
resonance in that region. Upon anchoring the Ag NPs, ZnO NRs show enhanced band
edge emission (380-400 nm) and the emission is further significantly increased in
Ag NP-anchored ZnO NTs. The on/off ratio and photoresponse properties of the UV
photodetectors are enhanced significantly after anchoring Ag NPs on the ZnO
nanostructures. It is believed that the near-field coupling of SPR causes an
optical enhancement of ZnO, whereas the bridging effect and hot-electron transfer
to the conduction band of ZnO by plasmonic Ag NPs, anchored in close proximity,
gives rise to a faster response of the photodetectors.
PMID- 28402291
TI - Multi-pulse flash light sintering of bimodal Cu nanoparticle-ink for highly
conductive printed Cu electrodes.
AB - In this work, bimodal Cu nano-inks composed of two different sizes of Cu
nanoparticles (NPs) (40 and 100 nm in diameter) were successfully sintered with a
multi-pulse flashlight sintering technique. Bimodal Cu nano-inks were fabricated
and printed with various mixing ratios and subsequently sintered by a flash light
sintering method. The effects of the flashlight sintering conditions, including
irradiation energy and pulse number, were investigated to optimize the sintering
conditions. A detailed mechanism of the sintering of bimodal Cu nano-ink was also
studied via real-time resistance measurement during the sintering process. The
sintered Cu nano-ink films were characterized using x-ray photoelectron
spectroscopy and scanning electron microscopy. From these results, it was found
that the optimal ratio of 40-100 nm NPs was found to be 25:75 wt%, and the
optimal multi-pulse flash light sintering condition (irradiation energy: 6 J cm
2, and pulse duration: 1 ms, off-time: 4 ms, and pulse number: 5) was found. The
optimally sintered Cu nano-ink film exhibited the lowest resistivity of 5.68
MUOmega cm and 5B adhesion level.
PMID- 28402292
TI - Preparation of Fe3O4/TiO2 magnetic mesoporous composites for photocatalytic
degradation of organic pollutants.
AB - Fe3O4/TiO2 magnetic mesoporous composites were synthesized through a sol-gel
method with tetra-n-butyl titanate as precursor and surfactant P123 as template.
The as-prepared Fe3O4/TiO2 composites were characterized by X-ray diffraction,
diffuse reflectance spectroscopy, nitrogen adsorption-desorption isotherm and
pore size distribution. The as-synthesized products were applied as
photocatalysis for the degradation of Acid Black ATT and tannery wastewater under
UV lamp irradiation. Fe3O4/TiO2-8 composites containing Fe3O4 of 8 wt% were
selected as model catalysts. The optimal catalyst dosage was 3 g/L in this
photocalytic system. The magnetic Fe3O4/TiO2 composites possessed good
photocatalytic stability and durability. This approach may provide a platform to
prepare a magnetic composite to optimize the catalytic ability.
PMID- 28402293
TI - Influence of relative air/water flow velocity on oxygen mass transfer in gravity
sewers.
AB - Problems related to hydrogen sulfide may be serious for both network stakeholders
and the public in terms of health, sustainability of the sewer structure and
urban comfort. H2S emission models are generally theoretical and simplified in
terms of environmental conditions. Although air transport characteristics in
sewers must play a role in the fate of hydrogen sulfide, only a limited number of
studies have investigated this issue. The aim of this study was to better
understand H2S liquid to gas transfer by highlighting the link between the mass
transfer coefficient and the turbulence in the air flow and the water flow. For
experimental safety reasons, O2 was taken as a model compound. The oxygen mass
transfer coefficients were obtained using a mass balance in plug flow. The mass
transfer coefficient was not impacted by the range of the interface air-flow
velocity values tested (0.55-2.28 m.s-1) or the water velocity values (0.06-0.55
m.s-1). Using the ratio between kL,O2 to kL,H2S, the H2S mass transfer behavior
in a gravity pipe in the same hydraulic conditions can be predicted.
PMID- 28402294
TI - Synthesis and characterization of a novel magnetic biochar from sewage sludge and
its effectiveness in the removal of methyl orange from aqueous solution.
AB - A novel magnetic biochar from sewage sludge (MSBC) using SrFe12O19 as magnetic
substrate was successfully synthesized under high-temperature and oxygen-free
conditions. Several techniques and methodologies (X-ray diffraction, Fourier
transform infrared spectroscopy and vibrating sample magnetometer) were used to
determine the surface functional groups and physicochemical properties of MSBC,
which showed that the MSBC combined the features of both SrFe12O19 and sludge
biochar (SBC). And then the adsorption behavior of methyl orange (MO) from
aqueous solution onto the MSBC was investigated. And the influence of variables
including pH, initial concentration of MO, adsorbent dosage and contact time was
studied in detail. The optimal adsorption amount of MO (149.18 mg.g-1) was
obtained with 600 MO mg.L-1, 2 MSBC g.L-1, at pH of 5 for 40 min. The equilibrium
data were evaluated using Langmuir and Freundlich isotherms. The Langmuir model
better described the absorption of MO. Besides, the kinetic data were analyzed
using pseudo-first-order and pseudo-second-order equations, and the pseudo-second
order exhibited the better fit for the kinetic studies (R2 = 0.9982). This study
showed that MSBC could be utilized as an efficient, magnetically separable
adsorbent for the environmental cleanup.
PMID- 28402295
TI - Kinetics and mechanism of desilication reaction in sodium chromate solution using
sodium aluminate.
AB - It is essential to control silica levels in sodium chromate solution during the
process of electrolytic synthesis of sodium dichromate. On the basis of previous
work, the desilication conditions were systematically studied and pH was found to
have the most serious impact on the desilication process. The desilication rate
under optimal conditions obtained from the orthogonal experiment results was up
to 99.3%. Kinetic experiments showed that the desilication reaction was first
order in SiO2 concentration and the apparent activation energy was calculated to
be 22 kJ mol-1, which is far less than the reported values. The morphology and
structure of the desilication reaction product (DSP) were studied by scanning
electron microscope (SEM) and X-ray diffraction (XRD). SEM showed that DSP had a
loose etched structure. The pattern of XRD illustrated the crystallinity of DSP
increased along the duration of the experiment. The phase of DSP was mainly
Na6(AlSiO4)6. Based on the experimental data, the desilication mechanism has been
discussed. The hexameric aluminosilicate ions were produced by the reaction of
monomeric aluminosilicate ion, through hydrogen bond interaction, which was
formed by SiO2(OH)22- and Al(OH)4-.
PMID- 28402296
TI - Design of fine-bubble aeration systems for municipal WWTPs with high sea salt
concentrations.
AB - The impact of sea salt on the aeration coefficient kLa of fine-bubble aeration
systems was investigated in clean water and in a model substance for simulating
activated sludge. The investigations were carried out at laboratory and pilot
scale. Sea salt was dosed in the form of artificial seawater, real seawater or
simplified, by adding NaCl. The investigated media showed an increase of kLa with
rising sea salt concentrations up to 10 g/L. The ratio between kLa and sea salt
concentration is impaired by the air flow rate and the type of applied diffusers.
Literature data show that the favourable effect of sea salt on kLa can also be
found in the activated sludge of conventional municipal wastewater treatment
plants. The results of this study allow the derivation of salt correction
equations to be used in the design of fine-bubble aeration systems for taking
into account the favourable impact of sea salt on kLa. By that means, a more
precise design of respective systems will be enabled.
PMID- 28402297
TI - Functionalized carbon nanotubes based filters for chromium removal from aqueous
solutions.
AB - This investigation examines the filtration efficiency of chromium from aqueous
solution using two types of commercial multiwalled carbon nanotubes (MWCNTs)
(Taunit-M (TM) and Taunit-MD (TMD)). These MWCNTs were modified using two
complementary treatments, purification (using a mixture of hydrochloric acid and
hydrogen peroxide) and functionalization (using nitric acid). The effect of these
treatments on the morphology of MWCNT Taunit filters was characterized by
scanning electron microscopy and energy dispersive X-ray spectroscopy to estimate
the outer diameter distribution and element content deposited on filters. Effects
of different parameters, i.e., carbon nanotube filter mass, concentration of
chromium in aqueous solution, and pH of aqueous solution, on removal of this
heavy metal were determined. From these investigations, the removal efficiency of
chromium could reach 97% for modified TM and 70% for modified TMD at
concentration of 10 ppm, suggesting that modified TM is an excellent adsorbent
for chromium removal from aqueous solutions and more efficient than modified TMD.
A significant increase in chromium removal by modified TM at pH = 2 has been
observed compared with higher pH values. It was found that modified TM filters
can be reused through many cycles of regeneration with high performance. Modified
TM filters may be a promising candidate for heavy metal ion removal from
industrial wastewater.
PMID- 28402298
TI - Bioremediation of methylene blue dye using Bacillus subtilis MTCC 441.
AB - Methylene blue (MB) commonly found in the textile industry effluent has been
chosen as a model dye to investigate bioremediation using Bacillus subtilis MTCC
441. Both free cells and calcium alginate immobilized cells have been used to
remove MB from the effluent. The operating variables of initial concentration of
dye (20-60 mg/L), inoculum size (4-8%) and temperature (25-35 degrees C) have
been varied judiciously during the kinetic study in a batch contactor. A maximum
removal of 91.68% is obtained when 20 mg/L MB solution was inoculated with 8%
inoculum and cultured for 6 h at 30 degrees C. Continuous removal of MB has been
studied in a fixed bed contactor using immobilized cells as packing materials.
Influent concentration (10-30 mg/L) was varied and breakthrough parameters have
been determined. With increase in influent concentration from 10 mg/L to 30 mg/L,
percentage removal of dye decreases from 72.44% to 49.62%.
PMID- 28402299
TI - Influences of rainfall variables and antecedent discharge on urban effluent
concentrations and loads in wet weather.
AB - For storm drainages inappropriately connected with sewage, wet weather discharge
is a major factor that adversely affects receiving waters. A study of the wet
weather influences of rainfall-discharge variables on storm drainages connected
with sewage was conducted in the downtown Shanghai area (374 ha). Two indicators,
event mean concentration (EMC) and event pollutant load per unit area (EPL), were
used to describe the pollution discharge during 20 rain events. The study showed
that the total rainfall and discharge volume were important factors that affect
the EMCs and EPLs of the chemical oxygen demand, total phosphorus, and especially
those of NH4+-N. The pollutant concentrations at the beginning of the discharge
and the discharge period were also major factors that influence the EMCs of these
three pollutants. Regression relationships between the rainfall-discharge
variables and discharge volume/ EPLs (R2 = 0.824-0.981) were stronger than the
relationships between the rainfall-discharge variables and EMCs. These regression
equations can be considered reliable in the system, with a relative validation
error of less than +/-10% for the discharge volume, and less than +/-20% for the
EPLs. The results presented in this paper provide guidance for effectively
controlling pollution in similar storm drainages.
PMID- 28402300
TI - Studies on the adsorption of amoxicillin on multi-wall carbon nanotubes.
AB - This study examined the feasibility of removing amoxicillin (AMO) from aqueous
solutions using multi-wall carbon nanotubes. The equilibrium adsorption data were
analyzed using four widely applied isotherms: Langmuir, Freundlich, Temkin, and
Dubinin-Radushkevich. The results showed that the Langmuir isotherm model fits
well the obtained experimental data. The adsorption process followed the pseudo
second-order model. The activation energy was found to be 19 kJ/mol. The Standard
free energy changes, DeltaG0, values were negative; the standard enthalpy change
(DeltaH0), and standard entropy change (DeltaS0) values of the process were 4
kJ/mol and 36 J/mol.K. Results suggested that the AMO adsorption on carbon
nanotubes was a spontaneous process.
PMID- 28402301
TI - Comparison of the methane production potential and biodegradability of kitchen
waste from different sources under mesophilic and thermophilic conditions.
AB - The methane production potential of kitchen waste (KW) obtained from different
sources was compared through mesophilic and thermophilic anaerobic digestion. The
methane yields (MYs) obtained with the same KW sample under different
temperatures were similar, whereas the MYs obtained with different samples
differed significantly. The highest MY obtained in S7 was 54%-60% higher than the
lowest MY in S3. The modified Gompertz model was utilized to simulate the methane
production process. The maximum production rate of methane under thermophilic
conditions was 2%-86% higher than that under mesophilic conditions. The
characteristics of different KW samples were studied. In the distribution of
total chemical oxygen demand, the diversity of organic compounds of KW was the
most dominant factor that affected the potential MYs of KW. The effect of the C/N
and C/P ratios or the concentration of metal ions was insignificant. Two typical
methods to calculate the theoretical MY (TMY) were compared, the organic
composition method can simulate methane production more precisely than the
elemental analysis method. Significant linear correlations were found between
TMYorg and MYs under mesophilic and thermophilic conditions. The organic
composition method can thus be utilized as a fast technique to predict the
methane production potential of KW.
PMID- 28402302
TI - Odorous volatile organic compound (VOC) emissions from ageing anaerobically
stabilised biosolids.
AB - Opportunities for the beneficial re-use of biosolids are limited by nuisance
odour emissions. Volatile organic compounds (VOCs) from anaerobically stabilised
biosolids were measured to identify compounds that could contribute to the
overall odour character of nuisance emissions. Flux hood sampling and chemical
analysis were used to identify VOCs emitted from biosolids as they were stored in
ambient conditions. Compounds emitted varied as the biosolid cakes were stored
for a period of 50 days. VOCs detected in the biosolids are likely to occur from
catchment sources as well as abiotic and biotic generation in the wastewater
processing and the biosolids as they are stored. Odour activity values (OAVs)
were used to compare odorants. Trimethylamine was the only VOC detected that
exceeded the sulfur compounds in terms of OAVs. Other compounds such as limonene,
ethyl methyl benzene and acetic acid were detected at concentrations exceeding
their olfactory detection limits, however at lower OAVs than sulfur compounds.
PMID- 28402303
TI - Ferrrate(VI) and freeze-thaw treatment for oxidation of hormones and inactivation
of fecal coliforms in sludge.
AB - This study examined the individual and combined effects of potassium ferrate(VI)
additions and freeze-thaw conditioning for the treatment and dewatering of
wastewater sludge in cold climates, with particular focus on the inactivation of
fecal coliforms and oxidation of estrogens, androgens, and progestogens. The
first phase of the study evaluated the effects of potassium ferrate(VI) pre
treatment followed by freeze-thaw at -20 degrees C using a low (0.5 g/L) and
high (5.0 g/L) dose of potassium ferrate(VI). The results showed that pre
treatment of anaerobically digested sludge with 5 g/L of potassium ferrate(VI)
reduced the concentration of fecal coliforms in the sludge cake to below 100
MPN/g DS. The second phase evaluated the ability of ferrate(VI) to oxidise
selected hormones in sludge. Anaerobically digested sludge samples were spiked
with 10 different hormones: estrone (E1), 17alpha-estradiol, 17beta-estradiol
(E2), estriol (E3), 17alpha-ethinylestradiol (EE2), equilin, mestranol,
testosterone, norethindrone and norgestrel in two groups of low (3-75 ng/mL) and
high (12-300 ng/L) concentration ranges of hormones. The samples were treated
with either 0.5 or 1.0 g/L of potassium ferrate(VI), and hormone concentrations
were measured again after treatment. Potassium ferrate(VI) additions as low as
1.0 g/L reduced the concentration of estrogens in sludge. Potassium ferrate(VI)
additions of 0.5 and 1.0 g/L were less effective at reducing the concentrations
of androgens and progestogens. Increasing ferrate(VI) dose would likely result in
more substantial decreases in the concentrations of fecal coliforms and hormones.
The results of this study indicate that the combined use of freeze-thaw and
ferrate(VI) has the potential to provide a complete sludge treatment solution in
cold regions.
PMID- 28402304
TI - Adsorption of methyl orange from aqueous solution using chitosan/diatomite
composite.
AB - A novel chitosan/diatomite composite was prepared by a simple mixture in the mass
ratio to remove methyl orange (MO) from aqueous media in this study. The
composite adsorbent was characterized by Fourier transform infrared spectroscopy
and scanning electron microscopy analysis. The parameters to influence the
adsorption of MO were studied under such conditions as kinetics, adsorption
isotherm, pH effect, and thermodynamics. The results revealed that adsorption of
MO was initially rapid and the equilibrium time was reached after 40 min. The
optimal value of the pH was 5.0 for better adsorption. The equilibrium data were
well fitted to the Langmuir isotherm compared to the Freundlich isotherm, and
exhibited the highest capacity and a removal rate of 88.37% under an initial dye
concentration of 50 mg/L. The kinetic data were well described by the pseudo
second order model. The thermodynamic calculations revealed that the sorption was
viable, spontaneous, and exothermic under the conditions studied. In addition,
the chitosan/diatomite composite had good adsorption and desorption performance
with respect to reusability after six cycles. These results showed that the
chitosan/diatomite could be considered as a potential adsorbent for the removal
of MO in aqueous solution.
PMID- 28402305
TI - The binding of metal ions to molecularly-imprinted polymers.
AB - Imprinting polymerization is a flexible method to make resins specific for
different compounds. Imprinting polymerization involves the polymerization of the
resin in the presence of a template, here cadmium ions or arsenate. The template
is then removed by washing, leaving specific binding sites in the resin. In water
treatment, the removal of toxic metal ions is difficult due to the limited
affinity of these ions to ion exchange resins. Imprinting polymerization of ion
exchange resins is used to develop resins with high capacity and some selectivity
for cadmium ions or arsenate for water treatment that still function as general
ion-exchange resins. A minimum binding capacity of 325 meq/g was achieved for
cadmium ions. Competition experiments elucidate the type of bonds present in the
imprinting complex. The capacity and bond types for the cadmium ions and arsenate
were contrasted. In the case of cadmium, metal-ligand bonds provide significant
specificity of binding, although significant binding also occurs to non-specific
surface sites. Arsenate ions are larger than cadmium ions and can only bind via
ionic and hydrogen bonds, which are weaker than metal-ligand bonds. This results
in lower specificity for arsenate. Additionally, diffusion into the resin is a
limiting factor due to the larger size of the arsenate ion. These data elucidate
the bonds formed between metal ions and the imprinting sites as well as other
parameters that increase the capacity for heavy metals and arsenate.
PMID- 28402306
TI - Adsorptive removal of Rhodamine B from aqueous solution by nanoporous
polydivinylbenzene.
AB - Nanoporous polydivinylbenzene (PDVB) material has been successfully prepared via
the copolymerization of divinylbenzene monomers. The nanoporous PDVB was
characterized through N2 adsorption/desorption isotherms, Fourier transform
infrared spectroscopy, scanning electron microscopy, and thermogravimetric
analysis. The nanoporous PDVB as an adsorbent was applied for the removal of
Rhodamine B (RhB). The adsorption behavior of PDVB for the removal of RhB showed
that the isotherm data followed the Langmuir isotherm model and the kinetic
adsorption obeyed the pseudo-second-order model. Thermodynamic parameters
illustrated that the adsorption process was spontaneous and exothermic.
Interestingly, the spent nanoporous PDVB has excellent regenerative performance
through treating it with ethanol. These results revealed that PDVB might be an
excellent adsorbent for the removal of RhB from wastewater.
PMID- 28402307
TI - Potential of resource recovery in UASB/trickling filter systems treating domestic
sewage in developing countries.
AB - This paper aims to present perspectives for energy (thermal and electric) and
nutrient (N and S) recovery in domestic sewage treatment systems comprised of
upflow anaerobic sludge blanket (UASB) reactors followed by sponge-bed trickling
filters (SBTF) in developing countries. The resource recovery potential was
characterized, taking into account 114 countries and a corresponding population
of 968.9 million inhabitants living in the tropical world, which were grouped
into three desired ranges in terms of cities' size. For each of these clusters, a
technological arrangement flow-sheet was proposed, depending on their technical
and economic viability from our best experience. Considering the population
living in cities over 100, 000 inhabitants, the potential of energy and nutrient
recovery via the sewage treatment scheme would be sufficient to generate
electricity for approximately 3.2 million residents, as well as thermal energy
for drying purposes that could result in a 24% volume reduction of sludge to be
transported and disposed of in landfills. The results show that UASB/SBTF systems
can play a very important role in the sanitation and environmental sector towards
more sustainable sewage treatment plants.
PMID- 28402308
TI - Phyto-dewatering of sewage sludge using Panicum repens L.
AB - Experiments in the field environment have been conducted to study the growth of
Panicum repens L., an aquatic plant, in the sewage sludge matrix. The experiments
were also carried out to investigate the ability of this plant to dewater sewage
sludge to increase the capacity of conventional drying beds. In addition, the
ability of Panicum repens L. to reduce the sludge contents of certain elements
(copper (Cu), Iron (Fe), Sodium (Na), lead (Pb), and Zinc (Zn)) was also
investigated. All experiments were carried out in batch reactors. Different plant
coverage densities were tested (0.00 to 27.3 kg/m2). The liquid sewage sludge was
collected from a wastewater treatment plant in Helwan city, Cairo Governorate,
Egypt. The collected sludge represents a mixture of the primary sludge and waste
activated sludge before discharging into drying beds.
PMID- 28402309
TI - Cadmium ion adsorption by amine-modified activated carbon.
AB - Cadmium (Cd) is one of the most toxic metals found in water and sediments. In the
effort to develop an effective adsorbent for aqueous Cd removal, activated carbon
(AC) was modified with an amino-terminated organosilicon (3
aminopropyltrimethoxysilane, APS). Response surface methodology was used to
optimize selected operational parameters of adsorption of aqueous Cd by
considering a central composite design with three input variables, temperature of
the mixture solution, the contact time and feed ratio (APS/AC), on the surface
modification. Results demonstrated that the strong Cd-binding amine ligands were
effectively introduced onto the AC surfaces through the silanol reaction between
carbon surface functional groups (-COOH, -COH) and APS molecules. The optimized
preparation condition is 77 degrees C, 4 h and 2.1 ratio. The adsorbent
presented a favorable adsorption of the aqueous Cd(II).
PMID- 28402310
TI - Treatment of urea manufacturing facility effluent by Hopea odorata and Khaya
ivorensis.
AB - Phytoremediation is an environmentally friendly and sustainable alternative for
treatment of nitrogen-enriched wastewaters. In this study, Ta-khian (Hopea
odorata) and Lagos mahogany (Khaya ivorensis), two tropical timber plants, were
investigated for their performances in treatment of urea manufacturing factory
effluent with high nitrogen (N) content. Plant seedlings received four
concentrations of N (190, 240, 290 and 340 mg/L N) in laboratory-scale
constructed wetlands every 4 days for a duration of 8 weeks. The solution volumes
supplied to each container, amount of N recovered by plants and plant growth
characteristics were measured throughout the experiment. Results showed that Ta
khian plants were highly effective at reducing N concentration and volume of
water. A maximum of 63.05% N recovery was obtained by Ta-khian plants grown in
290 mg/L N, which was assimilated in the chlorophyll molecule structure and shoot
biomass. Significant positive correlations have been shown between N recovery
percentages and plant growth parameters. Ta-Khian plants can be applied as
suitable phytoremediators for mitigating N pollution in water sources.
PMID- 28402311
TI - Polishing of municipal secondary effluent using native microalgae consortia.
AB - This work evaluates the use of native microalgae consortia for a dual role:
polishing treatment of municipal wastewater effluents and microalgae biomass
feedstock potential for biodiesel or biofertilizer production. An initial
screening was undertaken to test N and P removal from secondary effluents and
biomass production by 12 consortia. A subsequent treatment was performed by
selected consortia (01 and 12) under three operational conditions: stirring (S),
S + 12 h of daily aeration (S + A) and S + A enriched with CO2 (S + AC). All
treatments resulted in compliance with environmental regulations (e.g. Directive
91/271/EEC) and high removal efficiency of nutrients: 64-79% and 80-94% of total
N and PO43--P respectively. During the experiments it was shown that pH
alkalinization due to microalgae growth benefits the chemical removal of ammonia
and phosphorus. Moreover, advantages of pH increase could be accomplished by
intermittent CO2 addition which in this research (treatment S + AC) promoted
higher yield and lipid concentration. The resulting dry biomass analysis showed a
low lipid content (0.5-4.3%) not ideal for biodiesel production. Moreover, the
high rate of ash (29.3-53.0%) suggests that biomass could be readily recycled as
a biofertilizer due to mineral supply and organic constituents formed by C, N and
P (e.g. carbohydrate, protein, and lipids).
PMID- 28402312
TI - Release of hydrogen sulfide in a sewer system under intermittent flow conditions:
the Eiceira case study, in Portugal.
AB - The presence and fate of hydrogen sulfide in wastewater systems were studied in
two stretches of an intercepting sewer system located in a coastal village, in
Portugal. A range of hydraulic parameters were obtained and liquid and gas phase
measurements were carried out, both continuously and through intensive sampling
campaigns. Upstream, where flow rates were relatively low, dissolved sulfide
concentrations around 12 mg S L-1 and hydrogen sulfide gas concentrations above
250 ppm were observed, along with limited corrosion damage. It is believed this
is due to the low relative humidity detected along the atmosphere of the studied
sewer system. Downstream, gas concentrations were always below 40 ppm. Despite
that, high signs of corrosion were detected, particularly in manholes with drop
structures. It is thought that condensation of spray produced by the fall is the
main cause of the phenomenon. Another relevant observation was the rapid decline
in dissolved sulfide contents along gravity trunk sewers following the discharge
of rising mains, with loss rates as high as 40 mg S L-1 h-1. Air-flow velocities
corresponded to 15-50% of wastewater flows, an observation which agrees with
other authors' publications addressing relatively small pipes and moderate water
flows.
PMID- 28402313
TI - Effects of carbon sources, COD/NO2--N ratios and temperature on the nitrogen
removal performance of the simultaneous partial nitrification, anammox and
denitrification (SNAD) biofilm.
AB - The aim of the present work was to evaluate the effects of carbon sources and
chemical oxygen demand (COD)/NO2--N ratios on the anammox-denitrification
coupling process of the simultaneous partial nitrification, anammox and
denitrification (SNAD) biofilm. Also, the anammox activities of the SNAD biofilm
were investigated under different temperature. Kaldnes rings taken from the SNAD
biofilm reactor were operated in batch tests to determine the nitrogen removal
rates. As a result, with the carbon source of sodium acetate, the appropriate
COD/NO2--N ratios for the anammox-denitrification coupling process were 1 and 2.
With the COD/NO2--N ratios of 1, 2, 3, 4 and 5, the corresponding NO2--N
consumption via anammox was 87.1%, 52.2%, 29.3%, 23.7% and 16.3%, respectively.
However, with the carbon source of sodium propionate and glucose, the anammox
bacteria was found to perform higher nitrite competitive ability than
denitrifiers at the COD/NO2--N ratio of 5. Also, the SNAD biofilm could perform
anammox activity at 15 degrees C with the nitrogen removal rate of 0.071 kg
total inorganic nitrogen per kg volatile suspended solids per day. These results
indicated that the SNAD biofilm process might be feasible for the treatment of
municipal wastewater at normal temperature.
PMID- 28402314
TI - Semicentralized greywater and blackwater treatment for fast growing cities: how
uncertain influent characteristics might affect the treatment processes.
AB - The SEMIZENTRAL infrastructure approach has been developed for fast growing
cities, to meet their challenges regarding water supply as well as biowaste and
wastewater (WW) treatment. The world's first full-scale SEMIZENTRAL Resource
Recovery reference plant has been implemented in Qingdao (PR China). Greywater
(GW) and blackwater (BW) are collected and treated separately. Measurement of
influent concentrations revealed significant differences, compared with the
design values. Values from the literature for GW and BW characteristics vary more
markedly than for municipal WW; recommended design values are still lacking.
Moreover, cross-connections between GW and BW can influence the influent
characteristics considerably. Consequences for the design of GW and BW treatment
are evaluated for boundary conditions, which require high effluent quality for
both treatment modules. Model calculations illustrate the significant influence
of uncertain WW characteristics on the required aeration basin volume and oxygen
demand for GW and BW treatment; however, uncertainties are considerably reduced
for the combination of these modules. Thus, a flexible design of the treatment
plant is required. A possible concept for such a design is presented.
PMID- 28402315
TI - Simultaneous use of iron and copper anodes in photoelectro-Fenton process:
concurrent removals of dye and cadmium.
AB - Photoelectro-Fenton (PEF) was carried out for concurrent removals of inorganic
and organic pollutants with simultaneous applications of two different anodes
(iron and copper). Cadmium and Direct Orange 26 (DO26) were selected as samples
of the contaminants of textile wastewater and influential parameters (pH, current
density, H2O2 dosage and electrolysis time) of PEF were evaluated on Cd and DO26
removals. Both mechanisms of coagulation and oxidation affected the removal of
both pollutants. Optimal conditions were achieved with pH = 4.0, current density
of 5 mA/cm2, 3 mM H2O2 and 40 min electrolysis time, and under these conditions,
the dye was completely removed and the Cd removal efficiency was about 80%.
Unlike H2O2, persulfate had no scavenging effect in high dosages. The effects of
different anions and two matrixes (tap water and wastewater) on Cd and dye
removals were investigated. The results showed that decolorization was reduced by
the phosphate and nitrate ions while chloride ion accelerated the decolorization
rate. In terms of Cd removal, no significant change was observed in the presence
of the anions except for phosphate ion. The sludge of PEF was assessed by Fourier
transform infrared, field emission scanning electron microscope and energy
dispersive X-ray spectroscopy.
PMID- 28402316
TI - Effect of anaerobic digestion and liming on plant availability of phosphorus in
iron- and aluminium-precipitated sewage sludge from primary wastewater treatment
plants.
AB - More efficient plant utilisation of the phosphorus (P) in sewage sludge is
required because rock phosphate is a limited resource. To meet environmental
legislation thresholds for P removal from wastewater (WW), primary treatment with
iron (Fe) or aluminium (Al) coagulants is effective. There is also a growing
trend for WW treatment plants (WWTPs) to be coupled to a biogas process, in order
to co-generate energy. The sludge produced, when stabilised, is used as a soil
amendment in many countries. This study examined the effects of anaerobic
digestion (AD), with or without liming as a post-treatment, on P release from Fe-
and Al-precipitated sludges originating from primary WWTPs. Plant uptake of P
from Fe- and Al-precipitated sludge after lime treatment but without AD was also
compared. Chemical characterisation with sequential extraction of P and a
greenhouse experiment with barley (Hordeum vulgare) were performed to assess the
treatment effects on plant-available P. Liming increased the P-labile fraction in
all cases. Plant P uptake increased from 18.5 mg pot-1 to 53 mg P pot-1 with
liming of Fe-precipitated sludge and to 35 mg P pot-1 with liming of the
digestate, while it increased from 18.7 mg pot-1 to 39 and 29 mg P pot-1 for the
Al-precipitated substrate and digestate, respectively. Thus, liming of untreated
Fe-precipitated sludge and its digestate resulted in higher P uptake than liming
its Al-precipitated counterparts. AD had a negative impact on P mobility for both
sludges.
PMID- 28402317
TI - Simultaneous and quantitative monitoring of co-cultured Pseudomonas aeruginosa
and Staphylococcus aureus with antibiotics on a diffusometric platform.
AB - Successful treatments against bacterial infections depend on antimicrobial
susceptibility testing (AST). However, conventional AST requires more than 24 h
to obtain an outcome, thereby contributing to high patient mortality. An
antibiotic therapy based on experiences is therefore necessary for saving lives
and escalating the emergence of multidrug-resistant pathogens. Accordingly, a
fast and effective drug screen is necessary for the appropriate administration of
antibiotics. The mixed pathogenic nature of infectious diseases emphasizes the
need to develop an assay system for polymicrobial infections. On this basis, we
present a novel technique for simultaneous and quantitative monitoring of co
cultured microorganisms by coupling optical diffusometry with bead-based
immunoassays. This simple integration simultaneously achieves a rapid AST
analysis for two pathogens. Triple color particles were simultaneously recorded
and subsequently analyzed by functionalizing different fluorescent color
particles with dissimilar pathogen-specific antibodies. Results suggested that
the effect of the antibiotic, gentamicin, on co-cultured Pseudomonas aeruginosa
and Staphylococcus aureus was effectively distinguished by the proposed
technique. This study revealed a multiplexed and time-saving (within 2 h)
platform with a small sample volume (~0.5 MUL) and a low initial bacterial count
(50 CFU per droplet, ~105 CFU/mL) for continuously monitoring the growth of co
cultured microorganisms. This technique provides insights into timely therapies
against polymicrobial diseases in the near future.
PMID- 28402319
TI - Pressure-induced structural and spin transitions of Fe3S4.
AB - Greigite (Fe3S4), isostructural with Fe3O4 has recently attracted great
scientific interests from material science to geology due to its complicated
structure and electronic and magnetic configurations. Here, an investigation into
the structural, magnetic and electronic properties of Fe3S4 under high pressure
has been conducted by first-principle calculations based on density functional
theory. The results show that a first-order phase transition of Fe3S4 would occur
from the inverse spinel (SP) structure to the Cr3S4-type (CS) structure at 3.4
GPa, accompanied by a collapse of 9.7% in the volume, a redistribution of iron
cations, and a half-metal to metal transition. In the CS-Fe3S4, Fe2+ located at
octahedral environment firstly undergoes a transition from high-spin (HS) state
to low-spin (LS) state at 8.5 GPa and Fe3+ subsequently does at 17 GPa. The
Equation of State for different phases of Fe3S4 are also determined. Our results
not only give some clues to explore novel materials by utilizing Fe3S4 but also
shed light on the fundamental information of Fe3O4, as well as those of other SP
AB2X4 compounds.
PMID- 28402318
TI - Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for
the treatment of Alzheimer's disease.
AB - Memory loss characterizes several neurodegenerative disorders, including
Alzheimer's disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and
elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising
therapeutic approach to treat cognitive deficits. However, PDE4 exists in several
isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here,
we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both
in vitro and in vivo using biochemical, electrophysiological and behavioural
analyses. GEBR-32a efficiently enhances cAMP in neuronal cultures and hippocampal
slices. In vivo pharmacokinetic analysis shows that GEBR-32a is rapidly
distributed within the central nervous system with a very favourable brain/blood
ratio. Specific behavioural tests (object location and Y-maze continuous
alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance
memory in AD transgenic mice and concomitantly rescues their hippocampal long
term potentiation deficit. Of great relevance, our preliminary toxicological
analysis indicates that GEBR-32a is not cytotoxic and genotoxic, and does not
seem to possess emetic-like side effects. In conclusion, GEBR-32a could represent
a very promising cognitive-enhancing drug with a great potential for the
treatment of Alzheimer's disease.
PMID- 28402320
TI - Prevalence of Modic changes in the lumbar vertebrae and their associations with
workload, smoking and weight in northern China.
AB - The distribution of Modic changes (MCs) in the lumbar endplates and the
evaluation of the relationships between MCs and risk factors are vital for
research into MCs. The T1-weighted and T2-weighted sagittal MRI scans of 210
patients who exhibited lumbar intervertebral disc degeneration were
retrospectively reviewed. The patients' weights, genders, smoking statuses,
physical activity levels and specific types of MC were recorded. The associations
between MCs and risk factors, such as physical work, smoking and body mass index,
were also analysed. MCs were observed in 47 patients (22.4%), including 16 males
and 31 females. Among all patients, the L5/S1 lumbar level was most likely to
suffer MCs. The MCs were predominantly type II. MCs occurred more often in obese
patients than in normal and overweight patients (P < 0.05). Patients whose jobs
required heavy labour were more likely to develop MCs (P < 0.05). Heavy work and
obesity were related to type III MCs more strongly than the other types (P >
0.05). Smoking seemed not to be correlated with the incidence of MCs (P > 0.05).
Gender, obesity and heavy work were strongly associated with MCs. Biomechanical
factors may play a critical role in the development of MCs.
PMID- 28402321
TI - Origin of high strength, low modulus superelasticity in nanowire-shape memory
alloy composites.
AB - An open question is the underlying mechanisms for a recent discovered
nanocomposite, which composed of shape memory alloy (SMA) matrix with embedded
metallic nanowires (NWs), demonstrating novel mechanical properties, such as
large quasi-linear elastic strain, low Young's modulus and high yield strength.
We use finite element simulations to investigate the interplay between the
superelasticity of SMA matrix and the elastic-plastic deformation of embedded
NWs. Our results show that stress transfer plays a dominated role in determining
the quasi-linear behavior of the nanocomposite. The corresponding microstructure
evolution indicate that the transfer is due to the coupling between plastic
deformation within the NWs and martensitic transformation in the matrix, i.e.,
the martensitic transformation of the SMA matrix promotes local plastic
deformation nearby, and the high plastic strain region of NWs retains
considerable martensite in the surrounding SMA matrix, thus facilitating
continues martensitic transformation in subsequent loading. Based on these
findings, we propose a general criterion for achieving quasi-linear elasticity.
PMID- 28402322
TI - Nutritional status in patients with phenylketonuria using glycomacropeptide as
their major protein source.
AB - BACKGROUND/OBJECTIVES: Low phenylalanine (PHE), glycomacropeptide-based protein
substitute (GMP) is an alternative to traditional L-amino acid supplements (AA)
used in the dietary management of phenylketonuria (PKU). In a retrospective,
longitudinal study, we report the nutritional status of PKU patients taking AA
and GMP. SUBJECTS/METHODS: Eleven PKU patients aged 27+/-10 years (1 HPA, 4 mild
and 6 classical PKU) on dietary treatment were evaluated (anthropometry, body
composition, blood pressure measurements, biochemical markers including vitamin,
mineral, lipids, carbohydrates and protein status/metabolism, and nutritional
intake assessment) at two different annual reviews. The mean time taking AA was
13+/-5 months and GMP 13+/-7 months. Blood phenylalanine (PHE) and tyrosine (TYR)
were analysed before and after GMP introduction. RESULTS: Both GMP and AA protein
substitutes provided similar protein equivalent intake (0.85 vs 0.75 g/kg/day,
P=0.182). In the GMP group, it contributed 57% (27-100%) of the protein
substitute intake (with AA delivering the rest of protein substitute intake),
providing an additional 34+/-12 mg/day PHE. Nutritional intake, anthropometry and
body composition measurements were similar in both the groups. Median blood PHE
did not change (P=0.594), although values within target range improved (36 vs
46%), but this was not statistically significant. Mean blood TYR increased
(52.0+/-19.2 vs 63.2+/-25.6 MUmol/l, P=0.033), and all biochemical markers
remained stable, except for a lower A1C haemoglobin (P=0.011). CONCLUSIONS:
Partial GMP contribution to total protein substitute intake did not affect
nutritional status in patients with PKU. Blood PHE control was not adversely
affected. The increased blood TYR after GMP introduction necessitates further
study.
PMID- 28402323
TI - Is it time to update body mass index standards in the elderly or embrace
measurements of body composition?
PMID- 28402324
TI - Vitamin B12 status in pregnant women and their infants in South India.
AB - BACKGROUND/OBJECTIVES: Vitamin B12 deficiency during pregnancy has been
associated with increased risk of adverse perinatal outcomes. However, few
studies have investigated the burden and determinants of vitamin B12 status in
young infants. This study was conducted to determine the associations between
maternal and infant vitamin B12 status. SUBJECTS/METHODS: Pregnant women
participating in a vitamin B12 supplementation trial in Bangalore, India, were
randomized to receive vitamin B12 (50 MUg) or placebo supplementation daily
during pregnancy through 6 weeks postpartum. All women received 60 mg of iron and
500 MUg of folic acid daily during pregnancy, as per standard of care. This
prospective analysis was conducted to determine the associations between maternal
vitamin B12 biomarkers (that is, plasma vitamin B12, methylmalonic acid (MMA) and
tHcy) during each trimester with infant vitamin B12 status (n=77) at 6 weeks of
age. RESULTS: At baseline (?14 weeks of gestation), 51% of mothers were vitamin
B12 deficient (vitamin B12<150 pmol/l) and 43% had impaired vitamin B12 status
(vitamin B12<150 pmol/l and MMA>0.26 MUmol/l); 44% of infants were vitamin B12
deficient at 6 weeks of age. After adjusting for vitamin B12 supplementation,
higher vitamin B12 concentrations in each trimester were associated with
increased infant vitamin B12 concentrations and lower risk of vitamin B12
deficiency in infants (P<0.05). After adjusting for vitamin B12 supplementation,
infants born to women with vitamin B12 deficiency had a twofold greater risk of
vitamin B12 deficiency (P<0.01). Higher maternal folate concentrations also
predicted lower risk of vitamin B12 deficiency in infants (P<0.05). Impaired
maternal vitamin B12 status, which combined both circulating and functional
biomarkers, was the single best predictor of infant vitamin B12 status.
CONCLUSIONS: Impaired maternal vitamin B12 status throughout pregnancy predicted
higher risk of vitamin B12 deficiency in infants, after adjusting for vitamin B12
supplementation. Future interventions are needed to improve vitamin B12 status
periconceptionally, and to ensure optimal vitamin B12 status and health outcomes
in pregnant women and their children.
PMID- 28402325
TI - The bioenergetics of inflammation: insights into obesity and type 2 diabetes.
AB - Diabetes mellitus is one of the most common chronic metabolic disorders
worldwide, and its incidence in Asian countries is alarmingly high. Type 2
diabetes (T2DM) is closely associated with obesity, and the staggering rise in
obesity is one of the primary factors related to the increased frequency of T2DM.
Low-grade chronic inflammation is also accepted as an integral metabolic adaption
in obesity and T2DM, and is believed to be a major player in the onset of insulin
resistance. However, the exact mechanism(s) that cause a persistent chronic low
grade infiltration of leukocytes into insulin-target tissues such as adipose,
skeletal muscle and liver are not entirely known. Recent developments in the
understanding of leukocyte metabolism have revealed that the inflammatory
polarization of immune cells, and consequently their immunological function, are
strongly connected to their metabolic profile. Therefore, it is hypothesized that
dysfunctional immune cell metabolism is a central cellular mechanism that
prevents the resolution of inflammation in chronic metabolic conditions such as
that observed in obesity and T2DM. The purpose of this review is to explore the
metabolic demands of different immune cell types, and identify the molecular
switches that control immune cell metabolism and ultimately function.
Understanding of these concepts may allow the development of interventions that
can correct immune function and may possibly decrease chronic low-grade
inflammation in humans suffering from obesity and T2DM. We also review the latest
clinical techniques used to measure metabolic flux in primary leukocytes isolated
from obese and T2DM patients.
PMID- 28402326
TI - Chocolate intake and diabetes risk in postmenopausal American women.
AB - BACKGROUND/OBJECTIVES: Recent long-term prospective cohort studies found inverse
associations between chocolate consumption and the risk of type 2 diabetes, but
provided conflicting evidence on the nature of the association among women. To
assess this association in a large cohort of American women. SUBJECTS/METHODS:
Multivariable Cox regression was used with the data from 92 678 postmenopausal
women in the prospective Women's Health Initiative study. Chocolate intake was
assessed by food frequency questionnaire. Incidence of type 2 diabetes was
determined by self-report of the first treatment with oral medication or insulin.
RESULTS: Among women free of diabetes at baseline, there were 10 804 cases,
representing an incidence rate of 11.7% during 13.1 years and 1 164 498 person
years of follow-up. There was no significant linear association between long-term
chocolate intake and type 2 diabetes risk, but there was significantly reduced
risk at moderate levels of intake. Compared to women who ate 1 oz. of chocolate
<1 time per month, those who ate this amount 1-<1.5 times per month, 1.5-<3.5
times per month, 3.5 times per month to <3 times per week and ?3 times per week
had hazard ratios of 0.97 (95% confidence interval: 0.92, 1.04), 0.92 (0.87,
0.98), 0.93 (0.88, 0.98) and 0.98 (0.92, 1.04) (P for linear trend=0.79). There
was only evidence of such inverse associations for women with below-median
physical activity (P for interaction <0.0001) and those with age<65 years
(P=0.01). CONCLUSIONS: We only found an inverse association between chocolate
consumption and type 2 diabetes at moderate levels of consumption in two
subgroups of postmenopausal women in the Women's Health initiative cohort.
PMID- 28402327
TI - Conserved G-matrices of morphological and life-history traits among continental
and island blue tit populations.
AB - The genetic variance-covariance matrix (G-matrix) summarizes the genetic
architecture of multiple traits. It has a central role in the understanding of
phenotypic divergence and the quantification of the evolutionary potential of
populations. Laboratory experiments have shown that G-matrices can vary rapidly
under divergent selective pressures. However, because of the demanding nature of
G-matrix estimation and comparison in wild populations, the extent of its spatial
variability remains largely unknown. In this study, we investigate spatial
variation in G-matrices for morphological and life-history traits using long-term
data sets from one continental and three island populations of blue tit
(Cyanistes caeruleus) that have experienced contrasting population history and
selective environment. We found no evidence for differences in G-matrices among
populations. Interestingly, the phenotypic variance-covariance matrices (P) were
divergent across populations, suggesting that using P as a substitute for G may
be inadequate. These analyses also provide the first evidence in wild populations
for additive genetic variation in the incubation period (that is, the period
between last egg laid and hatching) in all four populations. Altogether, our
results suggest that G-matrices may be stable across populations inhabiting
contrasted environments, therefore challenging the results of previous simulation
studies and laboratory experiments.
PMID- 28402328
TI - The phenotypic correlates and quantitative genetics of masculinization in the
rodent, Octodon degus.
AB - In some mammals, female characteristics have been shown to depend, in part, on
the intrauterine position during development of female fetuses relative to male
fetuses. Females developing in close proximity to males show behavioral,
physiological and life history characteristics that are masculinized. With the
exception of one inconclusive study, nothing is known of the genetic basis of
this phenomenon. In this paper, we reported an analysis of the quantitative
genetic basis of masculinization, as indicated by the anogenital distance (AGD)
at birth and weaning, in the rodent Octodon degus. Because AGD is related to
weight, we included a genetic analysis of pup weight at birth and weaning.
Pairwise correlations showed that AGD at birth varied negatively with litter size
and parturition number but positively with weaning AGD, birth weight, dam AGD and
percentage of males in the litter. AGD at weaning varied similarly except that it
tended to vary positively with litter size. Genetic (co)variances of AGD at birth
and weight at birth differed in females and males. In females, the best genetic
model included substantial effects of direct additive, additive maternal and a
negative additive genetic covariance between these two. In males, variances were
small and there was difficulty in discriminating between additive maternal and
common environmental variances. By weaning, genetic (co)variances had somewhat
declined in weight and were not statistically significant in AGD in either sex.
This paper showed the occurrence of both phenotypic and genetic components in
masculinization with effects being greater in females.
PMID- 28402329
TI - No evidence for loss of short-wavelength sensitive cone photoreceptors in normal
ageing of the primate retina.
AB - In old world primates including humans, cone photoreceptors are classified
according to their maximal sensitivity at either short (S, blue), middle (M,
green) or long (L, red) wavelengths. Colour discrimination studies show that the
S-cone pathway is selectively affected by age and disease, and psychophysical
models implicate their loss. Photoreceptors have high metabolic demand and are
susceptible to age or disease-related losses in oxygen and nutrient supply. Hence
30% of rods are lost over life. While comparable losses are not seen in cones, S
cones comprise less than 10% of the cone population, so significant loss would be
undetected in total counts. Here we examine young and aged primate retinae
stained to distinguish S from M/L-cones. We show there is no age-related cone
loss in either cone type and that S-cones are as regularly distributed in old as
young primates. We propose that S-cone metabolism is less flexible than in their
M/L counterparts, making them more susceptible to deficits in normal cellular
function. Hypoxia is a feature of the ageing retina as extracellular debris
accumulates between photoreceptors and their blood supply which likely impacts S
cone function. However, that these cells remain in the ageing retina suggests the
potential for functional restoration.
PMID- 28402330
TI - Injection-modulated polarity conversion by charge carrier density control via a
self-assembled monolayer for all-solution-processed organic field-effect
transistors.
AB - We demonstrated modulation of charge carrier densities in all-solution-processed
organic field-effect transistors (OFETs) by modifying the injection properties
with self-assembled monolayers (SAMs). The all-solution-processed OFETs based on
an n-type polymer with inkjet-printed Ag electrodes were fabricated as a test
platform, and the injection properties were modified by the SAMs. Two types of
SAMs with different dipole direction, thiophenol (TP) and pentafluorobenzene
thiol (PFBT) were employed, modifying the work function of the inkjet-printed Ag
(4.9 eV) to 4.66 eV and 5.24 eV with TP and PFBT treatments, respectively. The
charge carrier densities were controlled by the SAM treatment in both dominant
and non-dominant carrier-channel regimes. This work demonstrates that control of
the charge carrier densities can be efficiently achieved by modifying the
injection property with SAM treatment; thus, this approach can achieve polarity
conversion of the OFETs.
PMID- 28402331
TI - Performances of the hybrid between CyCa nucleocytplasmic hybrid fish and
scattered mirror carp in different culture environments.
AB - To improve the performance of growth traits and survival in common carp, CyCa
nucleocytoplasmic hybrid fish (C) was used as parental fish for hybridization
with Russian scattered mirror carp (R). Performances in morphological characters,
growth traits and survival rate were compared among the purebreds (CC &RR) and
crossbreds (RC &CR) at different time period in solitary and communal rearing
system, respectively. The results demonstrated that both RC and CR crossbreds
inherited the grey skin color type from the mirror carp, and got the full-scale
pattern from the CyCa nucleocytoplasmic hybrid fish, which suggested that the
grey color dominated to red color and full-scale dominated to scattered scale.
With respect to yield, the RC crossbreds perform quite great compared to the RR
and CC purebreds because they have quite high growth and survival rate. In
contrast to RC crossbreds, the CR crossbreds performed poorly in growth traits,
together with that crosses where scattered mirror carp was used as mother (RC and
RR) achieved the greatest performance for all growth traits, suggested that the
maternal influence also displayed an important role in growth traits. These
results indicated that the RC crossbreds will be a potential carp variety for
commercial production.
PMID- 28402332
TI - Deep Learning for Flow Sculpting: Insights into Efficient Learning using
Scientific Simulation Data.
AB - A new technique for shaping microfluid flow, known as flow sculpting, offers an
unprecedented level of passive fluid flow control, with potential breakthrough
applications in advancing manufacturing, biology, and chemistry research at the
microscale. However, efficiently solving the inverse problem of designing a flow
sculpting device for a desired fluid flow shape remains a challenge. Current
approaches struggle with the many-to-one design space, requiring substantial user
interaction and the necessity of building intuition, all of which are time and
resource intensive. Deep learning has emerged as an efficient function
approximation technique for high-dimensional spaces, and presents a fast solution
to the inverse problem, yet the science of its implementation in similarly
defined problems remains largely unexplored. We propose that deep learning
methods can completely outpace current approaches for scientific inverse problems
while delivering comparable designs. To this end, we show how intelligent
sampling of the design space inputs can make deep learning methods more
competitive in accuracy, while illustrating their generalization capability to
out-of-sample predictions.
PMID- 28402333
TI - MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory
neuroendocrine prostate cancer cells.
AB - Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate.
An understanding of decision-making between these two pathways is in its infancy.
Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in
psychiatric research. Emerging reports showed that overexpression MAOA is
associated with prostate cancer (PCa). Here, we show that MAOA is involved in
mediating neuroendocrine differentiation of PCa cells, a feature associated with
hormone-refractory PCa (HRPC), a lethal type of disease. Following recent reports
showing that NED of PCa requires down-regulation of repressor element-1 silencing
transcription factor (REST) and activation of autophagy; we observe that MAOA is
a novel direct target gene of REST. Reactive oxygen species (ROS) produced by
overexpressed MAOA plays an essential role in inhibiting apoptosis and activating
autophagy in NED PCa cells. MAOA inhibitors significantly reduced NED and
autophagy activation of PCa cells. Our results here show MAOA as a new decision
maker for activating autophagy and MAOA inhibitors may be useful as a potential
therapy for neuroendocrine tumors.
PMID- 28402335
TI - Elephants know when their bodies are obstacles to success in a novel transfer
task.
AB - The capacity to recognise oneself as separate from other individuals and objects
is difficult to investigate in non-human animals. The hallmark empirical
assessment, the mirror self-recognition test, focuses on an animal's ability to
recognise itself in a mirror and success has thus far been demonstrated in only a
small number of species with a keen interest in their own visual reflection.
Adapting a recent study done with children, we designed a new body-awareness
paradigm for testing an animal's understanding of its place in its environment.
In this task, Asian elephants (Elephas maximus) were required to step onto a mat
and pick up a stick attached to it by rope, and then pass the stick forward to an
experimenter. In order to do the latter, the elephants had to see their body as
an obstacle to success and first remove their weight from the mat before
attempting to transfer the stick. The elephants got off the mat in the test
significantly more often than in controls, where getting off the mat was
unnecessary. This task helps level the playing field for non-visual species
tested on cognition tasks and may help better define the continuum on which body-
and self-awareness lie.
PMID- 28402334
TI - Characterization of c-Maf+Foxp3- Regulatory T Cells Induced by Repeated
Stimulation of Antigen-Presenting B Cells.
AB - The role of B cells in the development of CD4+ regulatory T cells has been
emphasized recently. Our previous studies have demonstrated that the antigen
presenting splenic B cells converted naive CD4+CD25- T cells into CD4+CD25+Foxp3-
T cells without additional cytokines or chemicals with regulatory activity and
that referred to as Treg-of-B cells. The present study further showed that Treg
of-B cells increased the IL-10-producing population, and the expression of c-Maf,
inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte
associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell
contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and
CTLA4-mediated antigen-specific suppressive activity; moreover, the single
antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In
conclusion, these results suggest that repeated stimulation of B cells induced IL
10-producing CD4+Foxp3- regulatory T cells in a contact-dependent manner and
these Treg-of-B cells possess IL-10 and CTLA4-dependent suppressive function.
PMID- 28402336
TI - Lock-picks: fungal infection facilitates the intrusion of strangers into ant
colonies.
AB - Studies investigating host-parasite systems rarely deal with multispecies
interactions, and mostly explore impacts on hosts as individuals. Much less is
known about the effects at colony level, when parasitism involves host organisms
that form societies. We surveyed the effect of an ectoparasitic fungus, Rickia
wasmannii, on kin-discrimination abilities of its host ant, Myrmica scabrinodis,
identifying potential consequences at social level and subsequent changes in
colony infiltration success of other organisms. Analyses of cuticular
hydrocarbons (CHCs), known to be involved in insects' discrimination processes,
revealed variations in chemical profiles correlated with the infection status of
the ants, that could not be explained by genetic variation tested by
microsatellites. In behavioural assays, fungus-infected workers were less
aggressive towards both non-nestmates and unrelated queens, enhancing the
probability of polygyny. Likewise, parasitic larvae of Maculinea butterflies had
a higher chance of adoption by infected colonies. Our study indicates that
pathogens can modify host recognition abilities, making the society more prone to
accept both conspecific and allospecific organisms.
PMID- 28402337
TI - Bone Marrow Adipose Tissue Deficiency Increases Disuse-Induced Bone Loss in Male
Mice.
AB - Bone marrow adipose tissue (MAT) is negatively associated with bone mass. Since
osteoblasts and adipocytes are derived from the same precursor cells, adipocyte
differentiation may occur at the expense of osteoblast differentiation. We used
MAT-deficient KitW/W-v (MAT-) mice to determine if absence of MAT reduced bone
loss in hindlimb-unloaded (HU) mice. Male MAT- and wild-type (WT) mice were
randomly assigned to a baseline, control or HU group (n = 10 mice/group) within
each genotype and HU groups unloaded for 2 weeks. Femurs were evaluated using
micro-computed tomography, histomorphometry and targeted gene profiling. MAT-
mice had a greater reduction in bone volume fraction after HU than did WT mice.
HU MAT- mice had elevated cancellous bone formation and resorption compared to
other treatment groups as well as a unique profile of differentially expressed
genes. Adoptive transfer of WT bone marrow-derived hematopoietic stem cells
reconstituted c-kit but not MAT in KitW/W-v mice. The MAT- WT -> KitW/W-v mice
lost cancellous bone following 2 weeks of HU. In summary, results from this study
suggest that MAT deficiency was not protective, and was associated with
exaggerated disuse-induced cancellous bone loss.
PMID- 28402339
TI - Rapid crystallization during recycling of basaltic andesite tephra: timescales
determined by reheating experiments.
AB - Microcrystalline inclusions within microlite-poor matrix are surprisingly common
in low intensity eruptions around the world, yet their origin is poorly
understood. Inclusions are commonly interpreted as evidence of crystallization
along conduit margins. Alternatively, these clasts may be recycled from low level
eruptions where they recrystallize by heating within the vent. We conducted a
series of experiments heating basaltic andesite lapilli from temperatures below
the glass transition (~690 degrees C) to above inferred eruption temperatures
(>1150 degrees C) for durations of 2 to >60 minutes. At 690 degrees C < T < 800
degrees C, crystallization is evident after heating for ~20 minutes; at T > 800
degrees C, crystallization occurs in <5 minutes. At T >= 900 degrees C, all
samples recrystallize extensively in 2-10 minutes, with pyroxenes, Fe-oxides, and
plagioclase. Experimental crystallization textures closely resemble those
observed in natural microcrystalline inclusions. Comparison of inclusion textures
in lapilli from the active submarine volcano NW Rota-1, Mariana arc and subaerial
volcano Stromboli suggest that characteristic signatures of clast recycling are
different in the two environments. Specifically, chlorine assimilation provides
key evidence of recycling in submarine samples, while bands of oxides bordering
microcrystalline inclusions are unique to subaerial environments. Correct
identification of recycling at basaltic vents will improve (lower) estimates of
mass eruption rate and help to refine interpretations of eruption dynamics.
PMID- 28402338
TI - Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau
mice, a model of Alzheimer's disease-like tau pathology.
AB - Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary
tangles is one of the two neuropathological hallmarks of Alzheimer's disease
(AD). The majority of AD cases are sporadic with numerous environmental,
biological and genetic risks factors. Interestingly, insulin dysfunction and
hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia
and insulin dysfunction affect tau pathology, is not well understood. In this
study, we examined the effects of insulin deficiency on tau pathology in
transgenic hTau mice by injecting different doses of streptozotocin (STZ), a
toxin that destroys insulin-producing cells in the pancreas. One high dose of STZ
resulted in marked diabetes, and five low doses led to a milder diabetes. Both
groups exhibited brain tau hyperphosphorylation but no increased aggregation. Tau
hyperphosphorylation correlated with inhibition of Protein Phosphatase 2A (PP2A),
the main tau phosphatase. Interestingly, insulin injection 30 minutes before
sacrifice partially restored tau phosphorylation to control levels in both STZ
injected groups. Our results confirm a link between insulin homeostasis and tau
phosphorylation, which could explain, at least in part, a higher incidence of AD
in diabetic patients.
PMID- 28402340
TI - Windscapes and olfactory foraging in a large carnivore.
AB - The theoretical optimal olfactory search strategy is to move cross-wind.
Empirical evidence supporting wind-associated directionality among carnivores,
however, is sparse. We examined satellite-linked telemetry movement data of adult
female polar bears (Ursus maritimus) from Hudson Bay, Canada, in relation to
modelled winds, in an effort to understand olfactory search for prey. In our
results, the predicted cross-wind movement occurred most frequently at night
during winter, the time when most hunting occurs, while downwind movement
dominated during fast winds, which impede olfaction. Migration during sea ice
freeze-up and break-up was also correlated with wind. A lack of orientation
during summer, a period with few food resources, likely reflected reduced cross
wind search. Our findings represent the first quantitative description of
anemotaxis, orientation to wind, for cross-wind search in a large carnivore. The
methods are widely applicable to olfactory predators and their prey. We suggest
windscapes be included as a habitat feature in habitat selection models for
olfactory animals when evaluating what is considered available habitat.
PMID- 28402341
TI - A Novel Approach to Bone Reconstruction: The Wafer Technique.
AB - This study presents a novel technique based on guided bone regeneration and onlay
grafts for three-dimensional bone augmentation. This two-stage technique uses an
autogenous cortical bone plate and collagen membranes to form a barrier
containing a mixture of deproteinized bovine bone matrix, autologous blood, and
bone grafted from intraoral sites. Five patients were treated. At 6 months
postsurgery, a mean increase in bone volume of 1,062 mm3 was shown. Mean maximum
linear augmentation was 3.65 mm. Histologic analysis of the regenerated areas
revealed the presence of compact newly formed bone with no sign of inflammation.
A total of 13 implants were placed. The patients were satisfied, and
complications were not observed.
PMID- 28402342
TI - Survival Rates and Bone and Soft Tissue Level Changes Around One-Piece Dental
Implants Placed with a Flapless or Flap Protocol: 8.5-Year Results.
AB - The purpose of the current study was to determine the survival rates and to
measure marginal bone changes and peri-implant conditions 8.5 years after
placement of one-piece implants with an anodically oxidized surface (AOS). A
total of 52 subjects who received a one-piece implant with an AOS using a
flapless or flap protocol and completed a previous randomized clinical trial were
contacted for a recall visit 8.5 years after implant placement (T8.5). Implant
success and survival rates, probing pocket depth (PPD), presence of bleeding on
probing (BoP), papilla level, and incidence of complications and peri-implant
disease were assessed by a single, blinded examiner. A second blinded examiner
evaluated marginal bone level changes. Results for 8.5 years were compared to
those at the time of implant placement, implant loading (0.5 year), and 1 and 1.5
years follow-up. The results based on 28 patients who attended the follow-up
visit (half had flapless and half a flap protocol) showed a 100% implant survival
rate and a 96.4% implant success rate 8.5 years after implant placement using one
piece implants, with no difference in survival and success rates between the
flapless and the flap protocol. During the same follow-up period, a significant
increase in crestal bone height from 1.5 to 8.5 years was observed. Analysis
suggested decreasing mean levels of bone loss with time (P < .001). Moreover,
there was 0.8 to 1.0 mm of bone loss through year 1.5, which decreased to 0.3 mm
at 8.5 years (P < .05). There was no statistically significant difference in PPD
or BoP over time. Similar mean levels of PPD were found in flap and flapless
groups (mean [SD] = 2.4 [0.3] and 2.2 [0.4] mm, respectively [P = .18]), as well
as similar rates of BoP (22.8% vs 17.9%, respectively). Papilla levels increased
during the first year after implant loading. However, there was little additional
change between 1.5 and 8.5 years. A total of eight fractured porcelain crowns and
three crown loosenings were reported. One-piece implants with an AOS showed high
survival rates and stable marginal bone and periimplant soft tissue levels
regardless of whether a flapless or flap protocol was used.
PMID- 28402343
TI - Use of Allograft with Platelet Concentrate in the Treatment of Multiple Miller
Class III Gingival Recession Defects: Report of Three Cases.
AB - Three patients with multiple Miller Class III recession defects with substantial
bone loss were treated with hard tissue augmentation with the goal to prevent
future recessions. The surgery involved a full-thickness mucoperiosteal coronally
advanced flap, bone grafting, and primary flap closure. Freeze-dried bone
allograft (FDBA) in combination with plasma rich in growth factors (PRGF) was
grafted during the procedure. After more than 6 months, the treated sites showed
soft tissue maturation and esthetic tissue blending. Clinically, an increase in
convexity of alveolar ridge and soft tissue was observed, as well as a marked
reduction in recession depth and gain in width of keratinized mucosa. Cone beam
computed tomography showed a gain in buccal bone thickness. The use of FDBA in
combination with PRGF appears to have potential for the treatment of Miller Class
III defects by providing improved hard and soft tissue profiles.
PMID- 28402344
TI - Radiopacity of Luting Cements as a Potential Factor in Peri-implantitis: An In
Vitro Comparative Study.
AB - The aim of this study was to establish the radiopacity of cements used in implant
retained fixed partial dentures with respect to implant material, enamel, and
dentin. A sample of 10 specimens of 13 different cements, implants, enamel, and
dentin were prepared. Radiographs of the specimens and aluminum step wedges were
acquired. Mean gray values of specimens were measured using digital imaging
software. Kolmogorov-Smirnov and Shapiro-Wilk normality tests and independent t
test were used (P = .05). Implantlink Semi, Premier, and Dentotemp had the lowest
radiopacity values; GC FujiTemp LT, Multilink Implant, Poly-F Plus, Cavex
Temporary, and Panavia SA showed the highest. Within the limitations of the
study, cements containing zinc oxide and ytterbium-trifluoride can be recommended
for cementation of implant-retained restorations.
PMID- 28402345
TI - Mandibular Regional Anatomical Landmarks and Clinical Implications for Ridge
Augmentation.
AB - Mandibular ridge augmentation via guided bone regeneration in the atrophic
mandible is considered one of the most challenging scenarios for implant
supported oral rehabilitation. Uneventful wound healing has clearly demonstrated
its impact on the final regenerative outcome. Soft tissue management must be
precise and adequate to attain flap-free wound closure. Accordingly, it demands
exhaustive insight and expertise to avoid damaging the neighboring structures.
The cadaver study described herein discusses the mandibular morphologic landmarks
(ie, musculature, vascularization, innervation, and salivary glands) necessary to
safely perform regenerative procedures in the atrophic mandibular ridge, such as
vertical ridge augmentation and dental implant surgery. The potential
intraoperative complications are presented, as well as clinical implications of
which the clinician must be aware to prevent adverse surgical events during
regenerative surgery and implant placement in this anatomical region.
PMID- 28402346
TI - Tissue Engineering Therapy for Atrophic Maxilla Using Minimally Manipulated CD90
and CD105 Bone Marrow Stem Cells: A Case Report.
AB - Bone deficiencies in the jaws of edentulous patients limit the possibility of
successful placement and osseointegration of endosseous implants. Bone resorption
is defined as a vertical and horizontal loss of quality and quantity in the
residual bone ridges; lack of bone structure requires bone grafting procedures to
enable implant placement and to improve the function, predictability, and
longevity of implants. The objective of this case study was to demonstrate the
feasibility of a novel cell therapy treatment for localized jaw bone defects with
tissue repair cells composed of a mixture of bone marrow-derived cells, including
CD90+ mesenchymal stem cells and CD105+ monocytes/macrophages, and xenograft
blocks, in what would be a safe and efficacious approach to the regeneration of
localized craniofacial bone defects. The use of stem cells represents an
alternative that could offer improved results, better quality histologically, and
greater quantity in millimeters of tissue in bone regeneration.
PMID- 28402347
TI - Use of the Modified Apically Repositioned Flap Technique to Create Attached
Gingiva in Areas of No Keratinized Tissue: A Clinical and Histologic Evaluation.
AB - The complete absence of keratinized attached gingiva on the buccal surface of a
tooth can make the area more susceptible to gingival recession. The modified
apically repositioned flap (MARF) technique is an effective procedure to increase
the dimensions of attached gingiva in areas that present with some existing
keratinized tissue. The objective of this case report is to present long-term
clinical and histologic evidence that the MARF technique can be used to create
attached gingiva in areas that lack keratinized tissue.
PMID- 28402348
TI - Accuracy of Bone Sounding in Assessing Facial Osseous-Gingival Tissue
Relationship in Maxillary Anterior Teeth.
AB - The aim of this study was to evaluate the accuracy of bone sounding (BS) in
assessing the facial osseous-gingival tissue relationship (FOGTR) of failing
maxillary anterior teeth. Dental records of patients who received immediate
implant placement (IIP) at the maxillary anterior area were screened. Mid-FOGTR
prior to extraction (BS), and immediately after flapless extraction (direct bone
level [DBL] measurement) were analyzed. A total of 160 patients with 190
maxillary anterior teeth were included. The mean FOGTR obtained from BS and DBL
were 3.19 +/- 0.71 mm and 3.47 +/- 1.29 mm, respectively (P = .004). The two
measurements were identical 83.2% of the time, within 1-mm discrepancy 4.7% of
the time, and > +/- 1 mm discrepancy 12.1% of the time. When discrepancy was
observed, BS underestimated DBL 14.2% of the time and overestimated 2.6% of the
time. Though statistically significant, the correlation was weak (Pearson
correlation coefficient r = .238, P = .0018). BS is an acceptably accurate and
minimally invasive diagnostic tool for measuring FOGTR. However, while the mean
difference between BS and DBL measurement is small (0.28 mm), the large range of
difference can be alarming. Therefore, clinicians should always prepare
alternative treatment options for IIP prior to extraction.
PMID- 28402349
TI - Partial Extraction Therapies (PET) Part 2: Procedures and Technical Aspects.
AB - Part 1 of this series introduced the partial extraction therapies as a group of
techniques for ridge preservation at immediate implant placement and beneath
pontic sites. The concept proposes a paradigm shift away from extract and augment
toward partly retaining the tooth root to preserve the ridge and prevent
buccopalatal collapse. The revolutionary socket-shield technique was introduced
in 2010; however, there has been no follow-up literature to guide the clinician
in terms of procedural steps. While root submergence is well established, the
socket-shield and pontic shield are still in their clinical infancy and require
long-term clinical data before they can be proposed as routine in everyday
implant dentistry. Yet without sound knowledge on how to carry out the partial
extraction therapies, a global dental community cannot participate in their
application or contribute to the growing knowledge base. In this, the second part
of the series, the procedures for root submergence, socket-shield, and pontic
shield are addressed, step by step, supplemented with applicable guidelines as
the first such publication guiding the clinician to apply these root- and ridge
preservation techniques. Technical aspects and complication management are also
addressed.
PMID- 28402350
TI - Various Tip Applications and Temperature Changes of Er,Cr:YSGG-Laser Irradiated
Implants In Vitro.
AB - The impact of the laser tip on implant temperature when irradiating implants with
lasers to treat peri-implantitis has received little attention. The present study
was designed to assess the influence of two laser tips (sapphire chisel [MC3] and
radial firing perio [RFP]) on temperature change of an implant irradiated with an
Er,Cr:YSGG laser in vitro under various operational conditions. The results
suggest that Er,Cr:YSGG irradiation using either tip with supplemental cooling
can be a thermally safe approach to implant decontamination. However, use of the
RFP tip consistently resulted in a greater temperature rise. The MC3 tip thus may
be preferable to the RFP tip for open-flap implant debridement.
PMID- 28402351
TI - Dimensional Evaluation of Different Ridge Preservation Techniques: A Randomized
Clinical Study.
AB - The objective of this study was to quantitatively determine ridge contour changes
after different alveolar ridge preservation techniques. An initial total of 40
patients provided a final total of 35 single-gap extraction sites. After tooth
removal, the socket was subjected to one of four treatment modalities: placement
of a deproteinized bovine bone mineral (DBBM; Endobon) covered with a soft tissue
punch from the palate (Tx1); placement of DBBM without soft tissue punch (Tx2);
placement of an adsorbable collagen membrane (Osseoguard) covering the DBBM
(Tx3); and no additional treatment (control). Silicone impressions were obtained
before and 6 months after tooth extraction for quantitative-volumetric evaluation
on stone cast models. Bone quality and need for further bone augmentation were
also noted. Tx1 and Tx3 resulted in significantly less bucco-oral tissue loss
when compared to Tx2 and the control group. Premolar teeth and teeth extracted
for traumatic reasons revealed significantly less tissue loss. Using barrier
membranes or soft tissue punches in addition to placement of DBBM seems to be
advantageous to limit bucco-oral tissue atrophy. The clinical benefit, however,
is still questionable.
PMID- 28402352
TI - Peri-implantitis Induced by Stainless Steel Ligature in Beagle Dogs.
AB - The purpose of this study was to develop a new method for a peri-implantitis
model in beagle dogs in which a stainless steel ligature (SSL) was used
independently. A total of 36 Straumann dental implants were placed in six beagle
dogs 1 month after all mandibular premolars were extracted. After 3 months, SSLs
were placed in a submarginal position on the implants to induce peri-implantitis
and were not replaced during the 12-week tissue breakdown period. Inducing peri
implantitis in the beagles with an SSL is a rapid, effective, and simple method.
PMID- 28402353
TI - Peri-implant Soft Tissue Stability After Single Implant Restorations Using Either
Guided Bone Regeneration or a Connective Tissue Graft: A Randomized Clinical
Trial.
AB - The purpose of the present study was to compare two different surgical
procedures, connective tissue graft and guided bone regeneration, when applied in
conjunction with implant placement. Probing pocket depth and the recession depth
were recorded at the implant site after crown placement (T1) and at the 1-year
follow-up (T2), while the keratinized tissue height and the buccal mucosa
thickness were recorded at three different time points: at the time of implant
surgery (T0), after crown placement, and at the 1-year follow-up. No
statistically significant differences in peri-implant mucosa thickness,
recession, or other periodontal parameters were recorded at adjacent teeth.
PMID- 28402354
TI - Simultaneous Ridge Augmentation and Accelerated Molar Uprighting for Implant Site
Development: Two Case Reports with a Split-Mouth Design.
AB - Well-coordinated interdisciplinary dental treatments provide the best esthetic,
functional, and long-term results for patients. However, the length of such
treatment, which may involve orthodontics, ridge augmentation, and dental
implants, often deters patients from pursuing them. The two case reports
presented here aim to present the advantage of simultaneous orthodontic molar
uprighting and ridge augmentation procedures for future implant site development.
Selective decortication of the alveolar bone, performed simultaneously with bone
grafting, can accelerate the tooth uprighting process and synergistically reduce
treatment duration. Two cases with bilaterally missing mandibular first molars
were treated with this approach. In both patients, surgically accelerated
uprighting of molars occurred 1.6 times faster than the contralateral site, where
no surgery was performed. Additionally, ridge augmentation was successfully
achieved with 2.5 to 5 mm of horizontal bone gain during the molar uprighting
process.
PMID- 28402355
TI - Digitally Milled Metal Framework for Fixed Complete Denture with Metal Occlusal
Surfaces: A Design Concept.
AB - Implant-supported fixed complete dentures, often referred to as hybrid
prostheses, have been associated with high implant survival rates but also with a
high incidence of mechanical prosthetic complications. The most frequent of these
complications have been fracture and wear of the veneering material. The proposed
design concept incorporates the occlusal surfaces of the posterior teeth as part
of a digital milled metal framework by designing the posterior first molars in
full contour as part of the framework. The framework can be designed, scanned,
and milled from a titanium blank using a milling machine. Acrylic resin teeth can
then be placed on the framework by conventional protocol. The metal occlusal
surfaces of the titanium-countered molars will be at centric occlusion. It is
hypothesized that metal occlusal surfaces in the posterior region may reduce
occlusal wear in these types of prostheses. When the proposed design protocol is
followed, the connection between the metal frame and the cantilever part of the
prosthesis is reinforced, which may lead to fewer fractures of the metal
framework.
PMID- 28402356
TI - Patient-Based Comparison of Traditional Instruments and Piezoelectric Bone
Surgery in Osseous Resective Surgery.
AB - Osseous resective surgery has been widely advocated in the treatment of
periodontitis. The treatment traditionally has been done with rotary and manual
instruments, but piezoelectric devices recently have also been used. A total of
20 adult patients diagnosed with moderate to severe chronic periodontitis were
selected. A split-mouth study design was conducted such that one sextant was
operated using piezoelectric bone surgery (test) and one with traditional
instruments (control) in two separate sessions. Patients were asked to evaluate
their perception of cold sensitivity, spontaneous pain, bleeding, swelling, and
chewing discomfort. Piezoelectric bone surgery seems to be tolerated slightly
better than conventional rotary instruments.
PMID- 28402357
TI - Immediate Functional Loading of One-Piece Zirconia Implants in a Full-Arch
Maxillary Restoration: A Five-Year Case Report.
AB - Immediate loading has proven to be a predictable modality for restorations with
titanium dental implants. An increasing number of articles indicate that zirconia
implants might osseointegrate to a similar extent in this context. This 5-year
case report describes an outpatient maxillary restoration with eight immediately
loaded zirconia implants. Implantation followed extensive bone augmentation. At
the 5-year follow-up, all implants were still well osseointegrated clinically and
radiologically. No major bone loss or peri-implantitis had occurred in spite of
temporary insufficient patient compliance. More research and studies are needed
to confirm these results.
PMID- 28402358
TI - Surgical Treatment of a Peripheral Ossifying Fibroma and Reconstruction with a
Porcine Collagen Matrix: A Case Report.
AB - A 35-year-old woman was referred to the Department of Oral Medicine and Orofacial
Surgery after several recurrences of an ossifying fibroma (OF) that affected the
free and attached gingiva of the maxillary right central incisor. Surgery was
performed with a complete excision of the lesion together with the surrounding
healthy tissue up to the bone. To guide the healing of the anterior esthetic
framework and the excised tissues, a porcine collagen matrix as an alternative to
connective tissue graft was used. After an 18-month follow-up, the lesion had not
recurred and keratinized gingiva had formed around the area.
PMID- 28402359
TI - [HL2][P(1,2-O2C6Cl4)3] (L = THF, DMF): Bronsted acid initiators for the
polymerization of n-butyl vinyl ether and p-methoxystyrene.
AB - The development of solid, weighable Bronsted acids featuring the hexacoordinated
phosphorous(v) anion [TRISPHAT]- are reported. H(DMF)2[1] and H(THF)2[1] {[1]- =
[P(1,2-O2C6Cl4)3]-} were synthesized and fully characterized by 1H, 31P, 13C and
2D-NOESY NMR spectroscopy, X-ray crystallography, mass spectrometry and elemental
analysis. Both, H(DMF)2[1] and H(THF)2[1] are found to be suitable initiators for
the polymerization of n-butyl vinyl ether and p-methoxystyrene. Optimal
polymerization results for these single-component initiators were generally
obtained at -50 degrees C where high molecular weight polymers were isolated in
high yield. 1H NMR spectroscopic analysis and dynamic light scattering of
solutions of the isolated polymers provide evidence for a branched structure
which presumably arises from chain transfer.
PMID- 28402363
TI - On the validity of linear response approximations regarding the solvation
dynamics of polyatomic solutes.
AB - The time-dependent fluorescence of a chromophore can be calculated from either
nonequilibrium simulations, or, as long as linear response theory holds true,
from equilibrium solvent fluctuations in the ground or excited state if the
perturbation inflicted by the chromophore is small. The assumption of Gaussian
statistics, in contrast, links the nonequilibrium dynamics to solvent
fluctuations solely in the excited state, as long as the energy gap distribution
is Gaussian throughout the process. The validity of linear response theories on
the ground and excited state surface as well as Gaussian statistics is thoroughly
tested in this study by calculating the time-dependent Stokes shift of different
benzene-like solutes. The effect of the size of change in partial charges of the
solute, the multipolar order of charge distribution, the direction of change, as
well as the influence of different solvents on the validity of linear response
theory is examined by simulating 54 different systems. Calculation of the
Gaussian character of the energy distribution in equilibrium, as well as the time
evolution of the peak width in the nonequilibrium simulation sheds light on the
validity of Gaussian statistics in a nonstationary regime. We observed that a
large intermediate broadening of the width of the energy distribution correlates
with a failure of correlation functions to describe the nonequilibrium event.
These results are accompanied by analysis of higher order correlation functions,
as well as the structure of the solvents water, acetonitrile and methanol around
the solute, to yield a comprehensive view, as well as general guidelines, on when
and why equilibrium solvent fluctuations can correctly depict solvation dynamics.
PMID- 28402361
TI - Electronic characterization of Geobacter sulfurreducens pilins in self-assembled
monolayers unmasks tunnelling and hopping conduction pathways.
AB - The metal-reducing bacterium Geobacter sulfurreducens produces protein nanowires
(pili) for fast discharge of respiratory electrons to extracellular electron
acceptors such as iron oxides and uranium. Charge transport along the pili
requires aromatic residues, which cluster once the peptide subunits (pilins)
assemble keeping inter-aromic distances and geometries optimal for multistep
hopping. The presence of intramolecular aromatic contacts and the predominantly
alpha-helical conformation of the pilins has been proposed to contribute to
charge transport and rectification. To test this, we self-assembled recombinant,
thiolated pilins as a monolayer on gold electrodes and demonstrated their
conductivity by conductive probe atomic force microscopy. The studies unmasked a
crossover from exponential to weak distance dependence of conductivity and shifts
in the mechanical properties of the film that are consistent with a transition
from interchain tunneling in the upper, aromatic-free regions of the helices to
intramolecular hopping via aromatic residues at the amino terminus. Furthermore,
the mechanistic stratification effectively "doped" the pilins at the amino
terminus, favoring electron flow in the direction opposite to the helix dipole.
However, the effect of aromatic dopants on rectification is voltage-dependent and
observed only at the low (100 mV) voltages that operate in biological systems.
The results thus provide evidence for a peptide environment optimized for
electron transfer at biological voltages and in the direction needed for the
respiration of external electron acceptors. The implications of these results for
the development of hybrid devices that harness the natural abilities of the
pilins to bind and reduce metals are discussed.
PMID- 28402365
TI - Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal
stem cells for cancer therapy.
AB - A new platform constituted by engineered responsive nanoparticles transported by
human mesenchymal stem cells is here presented as a proof of concept. Ultrasound
responsive mesoporous silica nanoparticles are coated with polyethylenimine to
favor their effective uptake by decidua-derived mesenchymal stem cells. The
responsive-release ability of the designed nanoparticles is confirmed, both in
vial and in vivo. In addition, this capability is maintained inside the cells
used as carriers. The migration capacity of the nanoparticle-cell platform
towards mammary tumors is assessed in vitro. The efficacy of this platform for
anticancer therapy is shown against mammary tumor cells by inducing the release
of doxorubicin only when the cell vehicles are exposed to ultrasound.
PMID- 28402371
TI - Ligand-free nickel-catalyzed semihydrogenation of alkynes with sodium
borohydride: a highly efficient and selective process for cis-alkenes under
ambient conditions.
AB - We report a low-cost and efficient catalytic system, involving in situ generated
ligand-free Ni NPs, methanol and sodium borohydride, for the semihydrogenation of
alkynes under ambient conditions. This catalytic system exhibits remarkably high
activity, satisfactory cis-selectivity for internal alkynes, good stability and
general applicability.
PMID- 28402369
TI - Structural studies of the bond-orientational order and hexatic-smectic transition
in liquid crystals of various compositions.
AB - We report on the X-ray studies of freely suspended hexatic films of three
different liquid crystal compounds. By applying angular X-ray cross-correlation
analysis (XCCA) to the measured diffraction patterns the parameters of the bond
orientational (BO) order in the hexatic phase were directly determined. The
temperature evolution of the BO order parameters was analyzed on the basis of the
multicritical scaling theory (MCST). Our results confirmed the validity of the
MCST in the whole temperature range of the existence of the hexatic phase for all
three compounds. The temperature dependence of the BO order parameters in the
vicinity of the hexatic-smectic transition was fitted by a conventional power law
with a critical exponent beta ~ 0.1 of extremely small value. We found that the
temperature dependence of higher order harmonics of the BO order scales as the
powers of the first harmonic, with an exponent equal to the harmonic number. This
indicates a nonlinear coupling of the BO order parameters of different order. We
demonstrate that compounds of various compositions, possessing different phase
sequences at low temperatures, display the same thermodynamic behavior in the
hexatic phase and in the vicinity of the smectic-hexatic phase transition.
PMID- 28402372
TI - Bronsted acid-catalyzed, enantioselective synthesis of 1,4-dihydroquinoline-3
carboxylates via in situ generated ortho-quinone methide imines.
AB - A straightforward, catalytic, enantioselective approach toward the synthesis of a
broad range of 1,4-dihydroquinoline-3-carboxylates is described. Under phosphoric
acid catalysis in situ-generated ortho-quinone methide imines reacted with beta
keto esters to form the nitrogen heterocycles with good yields and
enantioselectivities in just one synthetic step under ambient reactions
conditions.
PMID- 28402373
TI - Depletion and double layer forces acting between charged particles in solutions
of like-charged polyelectrolytes and monovalent salts.
AB - Interaction forces between silica particles were measured in aqueous solutions of
the sodium salt of poly(styrene sulphonate) (PSS) and NaCl using the colloidal
probe technique based on an atomic force microscope (AFM). The observed forces
can be rationalized through a superposition of damped oscillatory forces and
double layer forces quantitatively. The double layer forces are modeled using
Poisson-Boltzmann (PB) theory for a mixture of a monovalent symmetric electrolyte
and a highly asymmetric electrolyte, whereby the multivalent coions represent the
polyelectrolyte chains. The effective charge of the polyelectrolyte is found to
be smaller than the bare number of charged groups residing on one polyelectrolyte
molecule. This effect can be explained by counterion condensation. The interplay
between depletion and double layer forces can be further used to predict the
phase of the depletion force oscillations. However, this picture holds only at
not too elevated concentrations of the polyelectrolyte and salt. At higher salt
concentrations, attractive van der Waals forces become important, while at higher
polyelectrolyte concentrations, the macromolecules adsorb onto the like-charged
silica interface.
PMID- 28402374
TI - Unveiling the effects of the in situ generated arene anion radical and imine
radical on catecholase like activity: a DFT supported experimental investigation.
AB - Two new dinuclear nickel(ii) complexes namely [Ni2(L1)2(OAc)2(H2O)2].CH3CN (1)
and [Ni2(L2)2(SCN)2(CH3OH)2].CH3OH (2) have been synthesized from the designed
Schiff-base ligand 4-bromo-2-[(2-hydroxy-1,1-dimethyl-ethylimino)-methyl]-phenol
(HL1) and its reduced analogue 4-bromo-2-[(2-hydroxy-1,1-dimethyl-ethylamino)
methyl]-phenol (HL2), respectively. Both 1 and 2 have been characterised by usual
physicochemical techniques (UV-Vis, FT-IR, ESI-MS study and single crystal XRD)
and their variable temperature magnetic study has been performed. The nickel(ii)
centres in the dinuclear complexes 1 and 2 are antiferromagnetically coupled
through participation of the bridging phenoxyl oxygen. In acetonitrile solution
both 1 and 2 retain their dinuclear structural integrity as is evident from the
ESI-MS study. The catecholase-like activity of 1 and 2 has been performed in
acetonitrile medium using 3,5-di-tert-butylcatechol (3,5-DTBC) as a model
substrate. Complex 1 shows a higher catalytic activity than that of complex 2.
The ESI-MS study suggests that dinuclear species undergo cleaving into a
mononuclear entity in the presence of 3,5-DTBC and that mononuclear species are
supposed to act as active catalysts in the catalytic cycle. The EPR study of
catalytic reactions confirms that organic radicals have been generated during
catalysis in both cases. However, in the case of complex 1 catalyzed reaction a
single isotropic signal at g = 1.97 is obtained which is most likely due to imine
radical formation. On the other hand, for complex 2 catalyzed reaction the
spectrum shows a signal with hyperfine splitting (g = 2.11, 2.05 and 1.9),
thereby suggesting the generation of a new radical i.e. an arene anion radical in
this study on catecholase activity. Extensive DFT calculations have been
performed to support the experimental observation and thus to put forward the
most probable mechanistic pathways operating in the two cases. The higher
efficiency of the imine radical pathway over the arene anion radical has been
rationalized by DFT calculations.
PMID- 28402376
TI - Effect of low water content in protic ionic liquid on ions electrosorption in
porous carbon: application to electrochemical capacitors.
AB - The effect of low water content (<20, 150, 1000, 10 000 ppm) in triethylammonium
bis[(trifluoromethyl)sulfonyl]imide - [(C2H5)3N+H][TFSI-] - protic ionic liquid
(PIL) on the performance of activated carbon (AC) electrodes as well as AC/AC
electrochemical capacitors (ECs) is reported. Under negative polarization,
hydrogen electrosorption onto carbon is enhanced along with the increase of water
content in PIL, whereas the resulting desorption peaks are shifted to lower
potential values, evidencing lower sorption energy when hydrogen is stored from
moisture containing PIL. Cyclic voltammetry (CV) investigations on PIL-based ECs
demonstrated that the evolution of the Stern layer nanostructure at positive and
negative potentials is asymmetrical. The results revealed comparable
electrochemical performance for PIL containing 150 and 1000 ppm of H2O, due to
similar operation of the positive electrode, where [TFSI-] anions are adsorbed in
the outer Helmholtz plane, and the negative one, where hydrogen is stored through
the reduction of the intermediate hydronium cation. By contrast, a cell with
"dry" PIL (<20 ppm of water) displayed a distinctive operation due to hydrogen
electrosorption directly through reduction of the protonated cation, and
selective adsorption of [TFSI-] anions, which occurs thanks to the high
polarizability and image force (IF) created by their induced charge.
Galvanostatic cycling with potential limitation (GCPL) showed comparable
capacitance values whatever the water content in PILs up to 1000 ppm, yet
electrochemical impedance spectroscopy (EIS) revealed higher capacitance as well
as better retention at higher frequencies with the PIL containing 150 ppm of
water. Hence, 150 ppm is reasoned to be an optimal value for diffusion and
adsorption of ions. The nature of current collectors (aluminum or stainless
steel) has a determining role in their polarization behavior, and consequently
the potential range of electrodes as well as ion diffusion into the activated
carbon porosity, influencing the observed capacitance values (CEIS/2.0V: 170 vs.
128 F g-1, for Al and SSt, respectively).
PMID- 28402377
TI - Interrelationship between TiO2 nanoparticle size and kind/size of dyes in the
mechanism and conversion efficiency of dye sensitized solar cells.
AB - In order to provide a comprehensive investigation of TiO2 nanoparticle size in
relation with different dye types in DSSCs, three sizes of TiO2 nanoparticles and
two different dye types including a porphyrin dye (T2) and a ruthenium dye (N3)
were synthesized. Steady state current-voltage (J-V) characteristics were
investigated for the fabricated DSSCs and the results demonstrated that the
optimum TiO2 nanoparticle size changed with the dye type. The obtained J-V data
were interpreted by cyclic voltammetry, UV-visible absorption spectroscopy, BET
measurement, DFT calculation, IPCE measurement and impedance spectroscopy. The
results for the N3 dye show that the surface area of the TiO2 nanoparticles is a
key factor for the N3 cells, which is restricted by TiO2 pore diameter and
surface state traps. In contrast, the density of localized states of the TiO2
film under the LUMO state of the porphyrin dyes is the dominating factor for the
performance of the solar cells, which is restricted by the surface area of the
TiO2 nanoparticles. These obtained results represent a significant advance in the
development of porphyrin, ruthenium and even solid electrolyte DSSCs.
PMID- 28402378
TI - Buckling behaviour of composites with double walled nanotubes from carbon and
phosphorus.
AB - Due to weak interactions among phosphorus atoms in black phosphorene, a nanotube
obtained by curling single-layer black phosphorus is not as stable as a carbon
nanotube (CNT) at finite temperature. In the present work, we recommend a new 1D
composite material with a double-walled nanotube (DWNT) from a black phosphorus
nanotube (BPNT) and a CNT. The dynamic response of the composite DWNTs is
simulated using a molecular dynamics approach. Effects of the factors including
temperature, slenderness and configurations of DWNTs on dynamic behavior of the
composite are discussed. Compared with a single-walled BPNT, the composite DWNTs
under uniaxial compression show some unique properties. When a BPNT is embedded
in a CNT which will not only isolate the BPNT from the ambient conditions, but
also improve the capability of axial deformation of the BPNT, the system will not
collapse rapidly even if the BPNT has been buckled.
PMID- 28402381
TI - Correction: High magnetisation, monodisperse and water-dispersible CoFe@Pt
core/shell nanoparticles.
AB - Correction for 'High magnetisation, monodisperse and water-dispersible CoFe@Pt
core/shell nanoparticles' by Ngo T. Dung et al., Nanoscale, 2017, DOI:
10.1039/c6nr09325f.
PMID- 28402382
TI - The electrochemical discrimination of pinene enantiomers by a cyclodextrin metal
organic framework.
AB - Pinene is a family of bicyclic monoterpenes found in nature, which exhibits
important applications in chemical industry and biomedicine; however, the
discrimination methods used for pinene enantiomers are still rare. The alpha- and
beta-pinene enantiomers were recognized and discriminated via an electrochemical
method for the first time based on a cyclodextrin metal-organic framework (CD
MOF) as an electrochemical chiral sensor.
PMID- 28402383
TI - Loss channels in triplet-triplet annihilation photon upconversion: importance of
annihilator singlet and triplet surface shapes.
AB - Triplet-triplet annihilation photon upconversion (TTA-UC) can, through a number
of energy transfer processes, efficiently combine two low frequency photons into
one photon of higher frequency. TTA-UC systems consist of one absorbing species
(the sensitizer) and one emitting species (the annihilator). Herein, we show that
the structurally similar annihilators, 9,10-diphenylanthracene (DPA, 1), 9-(4
phenylethynyl)-10-phenylanthracene (2) and 9,10-bis(phenylethynyl)anthracene
(BPEA, 3) have very different upconversion efficiencies, 15.2 +/- 2.8%, 15.9 +/-
1.3% and 1.6 +/- 0.8%, respectively (of a maximum of 50%). We show that these
results can be understood in terms of a loss channel, previously unaccounted for,
originating from the difference between the BPEA singlet and triplet surface
shapes. The difference between the two surfaces results in a fraction of the
triplet state population having geometries not energetically capable of forming
the first singlet excited state. This is supported by TD-DFT calculations of the
annihilator excited state surfaces as a function of phenyl group rotation. We
thereby highlight that the commonly used "spin-statistical factor" should be used
with caution when explaining TTA-efficiencies. Furthermore, we show that the
precious metal free zinc octaethylporphyrin (ZnOEP) can be used for efficient
sensitization and that the upconversion quantum yield is maximized when
sensitizer-annihilator spectral overlap is minimized (ZnOEP with 2).
PMID- 28402386
TI - StrandScript: evaluation of Illumina genotyping array design and strand
correction.
AB - Summary: After the introduction of high-throughput sequencing, genotyping arrays
continue to be a viable source for conducting large-scale genetic studies.
Currently, Illumina is one of the largest genotyping array manufacturers. One
technical issue that has always plagued the post-processing of Illumina
genotyping array data is the strand definition. Against convention, Illumina uses
their own definition of strand, which is inconsistent with the standard reference
forward and reverse definition. This issue has been a major obstacle in the
consistency of reporting, meta-analysis and correct interpretation of phenotype
association results. To date, the strand issue has not been adequately addressed,
prompting us to develop StrandScript, a tool that can convert all genotyping data
generated from Illumina genotyping arrays to the reference forward strand.
StrandScript works independently of the Illumina array version and is future
proof for newer Illumina array designs. Furthermore, StrandScript can examine an
Illumina genotyping array manifest file and can detect all problematic SNPs,
including SNPs with wrong RS ID and SNPs with mismatched probe sequences. Here,
we introduce StrandScript's design and development, and demonstrate its
effectiveness using real genotyping data. Availability and Implementation:
https://github.com/seasky002002/Strandscript. Contact: yan.guo.1@vanderbilt.edu.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28402385
TI - Does Choice of Influenza Vaccine Type Change Disease Burden and Cost
Effectiveness in the United States? An Agent-Based Modeling Study.
AB - Offering a choice of influenza vaccine type may increase vaccine coverage and
reduce disease burden, but it is more costly. This study calculated the public
health impact and cost-effectiveness of 4 strategies: no choice, pediatric
choice, adult choice, or choice for both age groups. Using agent-based modeling,
individuals were simulated as they interacted with others, and influenza was
tracked as it spread through a population in Washington, DC. Influenza
vaccination coverage derived from data from the Centers for Disease Control and
Prevention was increased by 6.5% (range, 3.25%-11.25%), reflecting changes due to
vaccine choice. With moderate influenza infectivity, the number of cases averaged
1,117,285 for no choice, 1,083,126 for pediatric choice, 1,009,026 for adult
choice, and 975,818 for choice for both age groups. Averted cases increased with
increased coverage and were highest for the choice-for-both-age-groups strategy;
adult choice also reduced cases in children. In cost-effectiveness analysis,
choice for both age groups was dominant when choice increased vaccine coverage by
>=3.25%. Offering a choice of influenza vaccines, with reasonable resultant
increases in coverage, decreased influenza cases by >100,000 with a favorable
cost-effectiveness profile. Clinical trials testing the predictions made based on
these simulation results and deliberation of policies and procedures to
facilitate choice should be considered.
PMID- 28402387
TI - Intensive Blood Pressure Control Improves Cognitive Performance: Pushing the
Envelope cum Judicia.
PMID- 28402389
TI - Impacts of the Psyllid Arytinnis hakani (Homoptera: Psyllidae) on Invasive French
Broom in Relation to Plant Size and Psyllid Density.
AB - The impacts of weed biological control agents may vary with plant ontogeny. As
plants grow, structural and chemical changes can alter plant resistance, which
may reduce herbivory via chemical or structural defenses, and plant tolerance,
which may enable plants to maintain fitness despite attack. Resistance and
tolerance generally increase as plants grow. Nonetheless, prerelease tests of
agent efficacy often overlook plant ontogeny. Here, we assess the performance and
impacts of a candidate biocontrol agent, the psyllid Arytinnis hakani (Loginova),
in relation to the age of its host plant, the invasive shrub French broom,
Genista monspessulana. We also examined whether the psyllid can consistently kill
plants when its densities are sufficiently high. Survival of psyllids to
adulthood and the timing of adult emergence did not differ between plant sizes,
indicating that performance of nymphs was not influenced by plant size. However,
adult psyllid survival was reduced on small plants, suggesting that nymphs and
adults responded differently to ontogenetic changes in plant quality. Psyllids
affected the growth of small and large plants similarly; all measured plant
growth parameters were lower in the presence of psyllids regardless of plant
size. In a separate experiment, effects on plant survival depended on psyllid
density, as higher realized densities of ~9 psyllids per cm stem length were
necessary to consistently kill plants. Thus, results suggest that the psyllid
would be equally effective on a range of plant sizes, particularly at high
densities, and show the potential of the psyllid to help control French broom in
California.
PMID- 28402388
TI - Cognitive Associates of Current and More Intensive Control of Hypertension:
Findings From the Hispanic Community Health Study/Study of Latinos.
AB - BACKGROUND: Hypertension control in Hispanics/Latinos lag behind general US
trends by 10-15%. Intensive systolic blood pressure (SBP) management <120 mm Hg
may significantly reduce morbidity/mortality risk in adults with hypertension;
less is known about cognition. We investigated cross-sectional associations of
cognition with observed hypertension control at currently recommended (SBP < 140
mm Hg) and more intensive (SBP < 120 mm Hg) levels using baseline data from the
Hispanic Community Health Study/Study of Latinos. METHODS: From this multicenter
cohort study, we focused on 1,735 Hispanic/Latino men and women ages 45-74 years
with hypertension and verified antihypertensive use. Verbal fluency, information
processing speed, learning, and memory were tested in Spanish or English.
RESULTS: Separate linear regressions revealed that being on 1 vs. >1
antihypertensive medication was not associated with cognition; however,
individuals with SBP controlled to currently recommended levels outperformed
individuals with uncontrolled SBP on verbal fluency [Beta = 1.44 (0.52), P <
0.01] and information processing speed [Beta = 3.01 (0.89), P < 0.001] in age
adjusted regression analyses; only information processing speed remained
significant (P < 0.05) after additional adjustments including acculturation,
health insurance, and other cardiovascular disease risk factors. When regrouping
individuals based on more intensive SBP control, individuals with levels <120 mm
Hg outperformed individuals with higher SBP on verbal fluency regardless of
adjustments (P < 0.01). More intensive rather than currently recommended levels
of control associated with higher verbal fluency performance regardless of
adjustments (P < 0.05). CONCLUSIONS: Individual cognitive test scores related to
distinct SBP management with more intensive management appearing more robust
against confounders. While cognitive associations with hypertension in
Hispanics/Latinos may be multifactorial, different levels of SBP control should
be considered in future prospective intervention studies.
PMID- 28402390
TI - Hybridization drives evolution of apomicts in Rubus subgenus Rubus: evidence from
microsatellite markers.
AB - Background and Aims: Rubus subgenus Rubus is a group of mostly apomictic and
polyploid species with a complicated taxonomy and history of ongoing
hybridization. The only polyploid series with prevailing sexuality is the series
Glandulosi , although the apomictic series Discolores and Radula also retain a
high degree of sexuality, which is influenced by environmental conditions and/or
pollen donors. The aim of this study is to detect sources of genetic variability,
determine the origin of apomictic taxa and validate microsatellite markers by
cloning and sequencing. Methods: A total of 206 individuals from two central
European regions were genotyped for 11 nuclear microsatellite loci and the
chloroplast trn L- trn F region. Microsatellite alleles were further sequenced in
order to determine the exact repeat number and to detect size homoplasy due to
insertions/deletions in flanking regions. Key Results: The results confirm that
apomictic microspecies of ser. Radula are derived from crosses between sexual
series Glandulosi and apomictic series Discolores , whereby the apomict acts as
pollen donor. Each apomictic microspecies is derived from a single distinct
genotype differing from the parental taxa, suggesting stabilized clonal
reproduction. Intraspecific variation within apomicts is considerably low
compared with sexual series Glandulosi , and reflects somatic mutation
accumulation. While facultative apomicts produce clonal offspring, sexual species
are the conduits of origin for new genetically different apomictic lineages.
Conclusions: One of the main driving forces of evolution and speciation in the
highly apomictic subgenus Rubus in central Europe is sexuality in the series
Glandulosi . Palaeovegetation data suggest that initial hybridizations took place
over different time periods in the two studied regions, and that the successful
origin and spread of apomictic microspecies of the series Radula took place over
several millennia. Additionally, the cloning and sequencing show that standard
evaluations of microsatellite repeat numbers underestimate genetic variability
considering homoplasy in allele size.
PMID- 28402393
TI - MetCirc: navigating mass spectral similarity in high-resolution MS/MS
metabolomics data.
AB - Summary: Among the main challenges in metabolomics are the rapid dereplication of
previously characterized metabolites across a range of biological samples and the
structural prediction of unknowns from MS/MS data. Here, we developed MetCirc to
comprehensively align and calculate pairwise similarity scores among MS/MS
spectral data and visualize these across a range of biological samples. MetCirc
comprises functionalities to interactively organize these data according to
compound familial groupings and to accelerate the discovery of shared metabolites
and hypothesis formulation for unknowns. As such, MetCirc provides a significant
advance to address biological questions in areas where chemodiversity plays a
role. Availability and Implementation: MetCirc , implemented in the open-source R
language, together with its vignette are available in the Bioconductor project
and at https://github.com/PlantDefenseMetabolism/MetCirc . Contact:
thomasnaake@googlemail.com or emmanuel.gaquerel@cos.uni-heidelberg.de.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28402391
TI - The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials
on Gametocyte Carriage and Transmission of Plasmodium falciparum: A Systematic
Review and Meta-analysis.
AB - Background: Artemisinin-based combination therapies (ACTs) have been widely
adopted as first-line agents to treat uncomplicated falciparum malaria due to
their activity against multidrug resistant parasites. ACTs may also disrupt
transmission through a direct antigametocyte effect, but the extent of this
effect is uncertain. We assessed the evidence for and estimated the effects of
the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs
on gametocyte clearance and transmission interruption. Methods: We searched
electronic databases for randomized controlled trials comparing AL to non-ACTs
that reported gametocyte counts or results of mosquito-feeding assays. Two
authors working independently assessed eligibility, extracted data, and evaluated
the risk of bias. We conducted meta-analyses using a random-effects model.
Results: We identified 22 eligible trials. The pooled odds of gametocytemia at 1
week were lower in AL- compared to non-ACT-treated participants (odds ratio [OR]
0.09; 95% confidence interval [CI], 0.06-0.15; I2 = 0.60, P < .01; 15 trials).
The odds of transmission to mosquitoes were also lower in AL treatment groups (OR
0.06; 95% CI, 0.00-0.47, P < .01 at 7 days post-treatment; 1 trial; OR 0.56; 95%
CI, 0.36-0.88, P = .01 at 14 days post-treatment; 1 trial). Conclusion: AL is
superior to non-ACTs in reducing gametocytemia, and, based on limited evidence,
abating transmission to mosquitoes. The transmission-limiting benefit of AL has
relevance for policymakers planning optimal utilization of control strategies,
including use of ACTs for malaria treatment and chemoprevention.
PMID- 28402392
TI - Caveolae-localized L-type Ca2+ channels do not contribute to function or
hypertrophic signalling in the mouse heart.
AB - Aims: L-type Ca2+ channels (LTCCs) in adult cardiomyocytes are localized to t
tubules where they initiate excitation-contraction coupling. Our recent work has
shown that a subpopulation of LTCCs found at the surface sarcolemma in caveolae
of adult feline cardiomyocytes can also generate a Ca2+ microdomain that
activates nuclear factor of activated T-cells signaling and cardiac hypertrophy,
although the relevance of this paradigm to hypertrophy regulation in vivo has not
been examined. Methods and results: Here we generated heart-specific transgenic
mice with a putative caveolae-targeted LTCC activator protein that was
ineffective in initiating or enhancing cardiac hypertrophy in vivo. We also
generated transgenic mice with cardiac-specific overexpression of a putative
caveolae-targeted inhibitor of LTCCs, and while this protein inhibited caveolae
localized LTCCs without effects on global Ca2+ handling, it similarly had no
effect on cardiac hypertrophy in vivo. Cardiac hypertrophy was elicited by
pressure overload for 2 or 12 weeks or with neurohumoral agonist infusion.
Caveolae-specific LTCC activator or inhibitor transgenic mice showed no greater
change in nuclear factor of activated T-cells activity after 2 weeks of pressure
overload stimulation compared with control mice. Conclusion: Our results indicate
that LTCCs in the caveolae microdomain do not affect cardiac function and are not
necessary for the regulation of hypertrophic signaling in the adult mouse heart.
PMID- 28402394
TI - Autophagy and TrkC/NT-3 signaling joined forces boost the hypoxic glioblastoma
cell survival.
AB - Glioblastoma multiform (GBM), the most common and aggressive primary brain tumor,
is characterized by a high degree of hypoxia and resistance to therapy because of
its adaptation capacities, including autophagy and growth factors signaling. In
this study, we show an efficient hypoxia-induced survival autophagy in four
different GBM cell lines (U87MG, M059K, M059J and LN-18) and an activation of a
particular neurotrophin signaling pathway. Indeed, the enhancement of both TrkC
and NT-3 was followed by downstream p38MAPK phosphorylation, suggesting the
occurrence of a survival autocrine loop. Autophagy inhibition increased the
hypoxia-induced expression of TrkC and its phosphorylated form as well as the
phosphorylation of p38, suggesting a complementary effect of the two processes,
leading to cell survival. Alone, autophagy inhibition reduced cellular growth
without inducing cell death. However, the double inhibition of autophagy and TrkC
signaling was necessary to bring cells to death as shown by PARP cleavage,
particularly important in hypoxia. Moreover, a very high expression of TrkC and
NT-3 was found in tumor sections from GBM patients, highlighting the importance
of neurotrophic signaling in GBM tumor cell survival. These data suggest that a
combined treatment targeting these two pathways could be considered in order to
induce the death of GBM cells.
PMID- 28402395
TI - mzML2ISA & nmrML2ISA: generating enriched ISA-Tab metadata files from
metabolomics XML data.
AB - Summary: Submission to the MetaboLights repository for metabolomics data
currently places the burden of reporting instrument and acquisition parameters in
ISA-Tab format on users, who have to do it manually, a process that is time
consuming and prone to user input error. Since the large majority of these
parameters are embedded in instrument raw data files, an opportunity exists to
capture this metadata more accurately. Here we report a set of Python packages
that can automatically generate ISA-Tab metadata file stubs from raw XML
metabolomics data files. The parsing packages are separated into mzML2ISA
(encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall,
the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata
substantially (capturing 90% of metadata on assay and sample levels), is much
less prone to user input errors, improves compliance with minimum information
reporting guidelines and facilitates more finely grained data exploration and
querying of datasets. Availability and Implementation: mzML2ISA & nmrML2ISA are
available under version 3 of the GNU General Public Licence at
https://github.com/ISA-tools. Documentation is available from
http://2isa.readthedocs.io/en/latest/. Contact: reza.salek@ebi.ac.uk or
isatools@googlegroups.com. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28402396
TI - Comparing the Efficacy of Drug Regimens for Pulmonary Tuberculosis: Meta-analysis
of Endpoints in Early-Phase Clinical Trials.
AB - Background: A systematic review of early clinical outcomes in tuberculosis was
undertaken to determine ranking of efficacy of drugs and combinations, define
variability of these measures on different endpoints, and to establish the
relationships between them. Methods: Studies were identified by searching PubMed,
Medline, Embase, LILACS (Latin American and Caribbean Health Sciences
Literature), and reference lists of included studies. Outcomes were early
bactericidal activity results over 2, 7, and 14 days, and the proportion of
patients with negative culture at 8 weeks. Results: One hundred thirty-three
trials reporting phase 2A (early bactericidal activity) and phase 2B (culture
conversion at 2 months) outcomes were identified. Only 9 drug combinations were
assessed on >1 phase 2A endpoint and only 3 were assessed in both phase 2A and 2B
trials. Conclusions: The existing evidence base supporting phase 2 methodology in
tuberculosis is highly incomplete. In future, a broader range of drugs and
combinations should be more consistently studied across a greater range of phase
2 endpoints.
PMID- 28402397
TI - Convergence and contrast in the community structure of Bacteria, Fungi and
Archaea along a tropical elevation-climate gradient.
AB - Changes in species richness along climatological gradients have been instrumental
in developing theories about the general drivers of biodiversity. Previous
studies on microbial communities along climate gradients on mountainsides have
revealed positive, negative and neutral richness trends. We examined changes in
richness and composition of Fungi, Bacteria and Archaea in soil along a 50-1000 m
elevation, 280-3280 mm/yr precipitation gradient in Hawai'i. Soil properties and
their drivers are exceptionally well understood along this gradient. All three
microbial groups responded strongly to the gradient, with community ordinations
being similar along axes of environmental conditions (pH, rainfall) and resource
availability (nitrogen, phosphorus). However, the form of the richness-climate
relationship varied between Fungi (positive linear), Bacteria (unimodal) and
Archaea (negative linear). These differences were related to resource-ecology and
limiting conditions for each group, with fungal richness increasing most strongly
with soil carbon, ammonia-oxidizing Archaea increasing with nitrogen
mineralization rate, and Bacteria increasing with both carbon and pH. Reponses to
the gradient became increasingly variable at finer taxonomic scales and within
any taxonomic group most individual OTUs occurred in narrow climate-elevation
ranges. These results show that microbial responses to climate gradients are
heterogeneous due to complexity of underlying environmental changes and the
diverse ecologies of microbial taxa.
PMID- 28402398
TI - The Health System and Policy Implications of Changing Epidemiology for Oral
Cavity and Oropharyngeal Cancers in the United States From 1995 to 2016.
AB - Oral cavity and oropharyngeal cancers are typically grouped under the general
term, "oral cancer." Yet, the incidence of oropharyngeal cancers is increasing in
the United States, while the incidence of oral cavity cancers has declined. These
2 distinct but conflated groups of oral cancers are attributed to different risk
factors. Incidence and survival trends were examined across US population groups
and by anatomical subsite. Disparities in incidence and survival by sex,
race/ethnicity, and subsite were identified. Risk factors are complex,
interactive, and not fully identified. Cancer control research illustrates health
disparities in access to care and patient outcomes. Database and supplemental
searches yielded 433 articles published between 1995 and 2016 characterizing
aspects of oral cancer epidemiology relating to incidence, survival, risk,
disparities, and cancer control. Oral cavity cancer survival in black men remains
the most intractable burden. Although understanding of oral cancer etiology is
improving, application to policy is limited. Cancer control efforts are diverse,
sporadic, limited in scope, and generally lacking in success, and they need
stratification by oral cavity cancers/oropharyngeal cancers. Further intervention
and epidemiologic research, improved workforce capacity, and integrated care
delivery are identified as important directions for public health policy.
Sustained, multilevel campaigns modeled on tobacco control success are suggested.
PMID- 28402399
TI - Reappraisal and new observations on atrial tachycardia ablated from the non
coronary aortic sinus of Valsalva.
PMID- 28402400
TI - Unplanned cardiac reoperations and interventions during long-term follow-up after
the Norwood procedure?.
AB - OBJECTIVES: Patients with hypoplastic left heart syndrome or related
malformations are predominantly treated with a 3-stage palliation. Anatomic or
physiologic problems can lead to unplanned additional surgical or catheter
interventions during single ventricle palliation. Changes in operative technique
may have an impact on the reoperation rate. METHODS: Between 1997 and 2014, 317
Norwood procedures were performed at our centre. A retrospective single centre
investigation was carried out concerning incidence, timing, indication and type
of unplanned interstage cardiac reoperations and catheter interventions during
follow-up of Norwood patients. Patients were followed from birth until the end of
2015. Cardiac procedures taking place at the time of the bidirectional Glenn or
Fontan procedure or heart transplantation were not included. RESULTS: Sixty-five
of the Norwood patients (20.5%) had at least one additional surgical cardiac
procedure. Nine patients (2.8%) needed open procedures prior to the Norwood
operations, 11.0% had procedures in the interstage I, 3.5% in the interstage II
and 9.1% of the Fontan patients had cardiac reoperations afterwards. Main
indications for unplanned surgery were insufficient pulmonary perfusion and
tricuspid regurgitation. Eighty-one patients (25.6%) had at least one interstage
catheter intervention during follow-up mainly addressing stenosis of the
pulmonary arteries, aortic arch stenosis or aortopulmonary collaterals.
CONCLUSIONS: The number of unplanned reoperations and interventions during staged
palliation is remarkably high showing surgical peaks in the interstage I and
after the Fontan procedure and an interventional peak in the interstage II.
Thorough early information of the parents about possibly anticipated additional
procedures is necessary.
PMID- 28402401
TI - A benchmarking project on the quality of previous guidelines about the management
of malignant pleural effusion from the European Society of Thoracic Surgeons
(ESTS) Pleural Diseases Working Group.
AB - OBJECTIVES: In the European Society of Thoracic Surgeons (ESTS) survey about
management of malignant pleural effusions (MPE), 56% of respondents are not
informed of any relevant clinical guidelines and 52%, who are aware of the
existence of guidelines, declared that they are in need of updating or revision.
The ESTS Pleural Diseases Working Group developed a benchmarking project on
quality of previous guidelines on the management of MPE. METHODS: The Appraisal
of Guidelines for Research and Evaluation (AGREE) II instrument was used to
assess each guideline. Each item was scored on a 7-point scale. Scores for each
domain were calculated. Economic data for the nations which have issued the
guidelines were collected from the Organisation for Economic Cooperation and
Development health statistics database. RESULTS: Six guidelines fitted the
inclusion criteria and were assessed. Five out of 6 guidelines were produced by a
multinational collaboration. Observers would recommend only 2 guidelines with
minimal modification. Two areas that received the best score were clarity of
presentation and scope and purpose (objectives and health questions target
population). The applicability of guideline domain had the lowest score.
Multivariate analysis demonstrated that clarity of presentation, international
guidelines and publication through medical journal were related to improved
scores. A strong correlation was observed between the measures of economic
status. CONCLUSIONS: The quality of guidelines assessed by the AGREE II criteria
was found to be extremely variable. Guidelines achieving higher AGREE II scores
were more likely to come from the European Union with the direct involvement of
scientific societies in their development. It was also recognized that some
fundamental unanswered questions remain about the management of MPE.
PMID- 28402403
TI - Preoperative stenting in oesophageal cancer has no effect on survival: a
propensity-matched case-control study.
AB - OBJECTIVES: Previous studies have shown a link between oesophageal stenting
before oesophagectomy and worse oncological outcomes. Our objective was to
determine the effect of preoperative self-expanding covered metallic stent (SEMS)
on survival, progression-free survival (PFS), operative time and complication
rates in oesophageal cancer (EC). METHODS: This study included EC patients
undergoing surgery between January 2006 and January 2014 with a cT2 tumour or
higher ( n = 174; 135 adenocarcinomas and 39 squamous cell carcinomas). We
propensity matched 1:1 a preoperative SEMS group ( n = 30) to a control group.
Despite the propensity matching, statistically non-significant residual covariate
imbalances persisted. Median follow-up time was 33 months (range: 0-118 months).
We performed Kaplan-Meier survival analysis for OS and PFS, the Student's t -test
for operative time and the chi-squared test for complication rates. RESULTS:
Median survival in the SEMS group was 28.5 months (range: 0-116 months) vs 34
months (4-118 months) in the control group and median PFS was 22 months (0-111
months) vs 27 (4-113 months) ( P = 0.748 and P = 0.764, respectively). Mean
operative times between groups were 436 min vs 375 min ( P = 0.017). No
differences emerged in intraoperative (23.3% vs 10%, P = 0.299), early (50.0% vs
46.7%, P = 1) or late complication rates (53.3% vs 43.3%, P = 0.606).
CONCLUSIONS: SEMS application has no significant effect on survival, PFS or
complications. Mean operative time was significantly higher in the SEMS insertion
group. We therefore conclude that preoperative SEMS insertion makes the operation
more challenging by increasing operative time, but is otherwise a feasible and
safe strategy in experienced centres as a bridge to surgery.
PMID- 28402402
TI - Evaluation of the Effectiveness and Cost-Effectiveness of Personalized
Surveillance After Colorectal Adenomatous Polypectomy.
AB - Lifetime risk of developing colorectal cancer is 5%, and 5-year survival at early
stage is 92%. Individuals with precancerous lesions removed at primary screening
are typically recommended surveillance colonoscopy. Because greater benefits are
anticipated for those with higher risk of colorectal cancer, scope for risk
specific surveillance recommendations exists. This review assesses published cost
effectiveness estimates of postpolypectomy surveillance to consider the potential
for personalized recommendations by risk group. Meta-analyses of incidence of
advanced neoplasia postpolypectomy for low-risk cases were comparable to those
without adenoma, with both rates under the lifetime risk of 5%. This group may
not benefit from intensive surveillance, which risks unnecessary harm and
inefficient use of often scarce colonoscopy capacity. Therefore, greater
personalization through deintensified strategies for low-risk individuals could
be beneficial. The potential for noninvasive testing, such as fecal
immunochemical tests, combined with primary prevention or chemoprevention may
reserve colonoscopy for targeted use in personalized risk-stratified
surveillance. This review appraised evidence supporting a program of personalized
surveillance in patients with colorectal adenoma according to risk group and
compared the effectiveness of surveillance colonoscopy with alternative
prevention strategies. It assessed trade-offs among costs, benefits, and adverse
effects that must be considered in a decision to adopt or reject personalized
surveillance.
PMID- 28402404
TI - Long-term outcome of surgical cryoablation for refractory ventricular tachycardia
in patients with non-ischemic cardiomyopathy.
AB - Aims: Limited data exist on the long-term outcome of patients (pts) with non
ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to
conventional therapies undergoing surgical ablation (SA). We aimed to investigate
the long-term survival and VT recurrence in NICM pts with VT refractory to
radiofrequency catheter ablation (RFCA) who underwent SA. Methods and results:
Consecutive pts with NICM and VT refractory to RFCA who underwent SA were
included. VT substrate was characterized in the electrophysiology lab and
targeted by RFCA. During SA, previous RFCA lesions/scars were identified and
targeted with cryoablation (CA; 3 min/lesion; target -150 degrees C). Follow-up
comprised office visits, ICD interrogations and the social security death index.
Twenty consecutive patients with NICM who underwent SA (age 53 +/- 16 years, 18
males, LVEF 41 +/- 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3,
hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied.
Percutaneous mapping/ablation in the electrophysiology lab was performed in 18
and 2 pts had primary SA. During surgery, 4.9 +/- 4.0 CA lesions/pt were
delivered to the endocardium (2) and epicardium (11) or both (7). VT-free
survival was 72.5% at 1 year and over 43 +/- 31 months (mos) (range 1-83mos),
there was only one arrhythmia-related death. There was a significant reduction in
ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 +/- 4.9
vs. 2.3 +/- 4.3 shocks/pt, P = 0.001). Conclusion: In select pts with NICM and VT
refractory to RFCA, SA guided by pre-operative electrophysiological mapping and
ablation may be a therapeutic option.
PMID- 28402405
TI - Sexual Networks, Dyadic Characteristics, and HIV Acquisition and Transmission
Behaviors Among Black Men Who Have Sex With Men in 6 US Cities.
AB - The role of sexual networks in the epidemiology of human immunodeficiency virus
(HIV) among black men who have sex with men (MSM) is poorly understood. Using
data from 1,306 black MSM in the BROTHERS Study (2009-2010) in the United States,
we examined the relationships between multiple sexual dyadic characteristics and
serodiscordant/serostatus-unknown condomless sex (SDCS). HIV-infected
participants had higher odds of SDCS when having sex at least weekly (odds ratio
(OR) = 2.41, 95% confidence interval (CI): 1.37, 4.23) or monthly (OR = 1.94, 95%
CI: 1.17, 3.24) versus once to a few times a year. HIV-uninfected participants
had higher odds of SDCS with partners met offline at sex-focused venues (OR =
1.79, 95% CI: 1.15, 2.78) versus partners met online. In addition, having sex
upon first meeting was associated with higher odds of SDCS (OR = 1.49, 95% CI:
1.21, 1.83) than was not having sex on first meeting, while living/continued
communication with sexual partner(s) was associated with lower odds of SDCS
(weekly: OR = 0.64, 95% CI: 0.47, 0.85; monthly: OR = 0.60, 95% CI: 0.44, 0.81;
yearly: OR = 0.58, 95% CI: 0.39, 0.85) versus discontinued communication. Persons
with primary/steady nonprimary partners versus commercial partners had lower odds
of SDCS regardless of HIV serostatus. This suggests the need for culturally
relevant HIV prevention efforts for black MSM that facilitate communication with
sexual partners especially about risk reduction strategies, including preexposure
prophylaxis.
PMID- 28402406
TI - Induction chemotherapy for T3N0M0 non-small-cell lung cancer increases the rate
of complete resection but does not confer improved survival.
AB - OBJECTIVES: The objective of this study was to evaluate outcomes of induction
therapy prior to an operation in patients with cT3 non-small-cell lung cancer
(NSCLC). METHODS: Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the
National Cancer Database who were treated with lobectomy or pneumonectomy were
stratified by treatment strategy: an operation first versus induction
chemotherapy. Propensity scores were developed and matched cohorts were
generated. Short-term outcomes included margin status, 30- and 90-day mortality
rates, readmission and length of stay. Survival analyses using Kaplan-Meier
methods were performed on both the unadjusted and propensity matched cohorts.
RESULTS: A total of 3791 cT3N0M0 patients were identified for inclusion, of which
580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients
treated with induction chemotherapy were younger, had a higher comorbidity burden
and were more likely to have private insurance (all P < 0.001). Following
matching, patients receiving induction chemotherapy were more likely to
subsequently undergo an open procedure (87.3 vs 77.8%, P = 0.005). These
patients were more likely to obtain R0 resection (93.1% vs 90.0%, P = 0.04) and
were thereby less likely to have positive margins at the time of resection (6.9%
vs 10.0%, P = 0.03). Patients who received induction therapy had higher rates of
90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival
between the groups. CONCLUSIONS : Despite yielding increased rates of R0
resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with
improved survival and should not be considered routinely. Further studies are
warranted to elucidate cohorts that may benefit from induction therapy.
PMID- 28402407
TI - Commentary on: CD30+ T Cells in Late Seroma May Not Be Diagnostic of Breast
Implant-Associated Anaplastic Large Cell Lymphoma.
PMID- 28402409
TI - Corrigendum to: '2016 ESC Guidelines for the diagnosis and treatment of acute and
chronic heart failure'.
PMID- 28402410
TI - The relationship between physical activity and self-rated health status in
European adolescents: Results of the EURO-URHIS 2 survey.
AB - Background: Engaging in regular physical activity has a beneficial impact on both
physical health and on subjective health indicators. The aims of this study were
(i) to assess the association between physical activity levels and self-reported
health status in European adolescents and (ii) to identify any differences in the
distribution of adolescents reporting good health between active and inactive
subjects across urban areas. The study sample comprised 13 783 15-year olds from
21 urban areas across Europe who participated in the European Urban Health
Indicators System Part 2 youth survey in 2010/11. Data collected on physical
activity levels, self-rated health status and covariates including gender, BMI,
socioeconomic status and sedentary behaviour were analyzed in a multivariable
logistic regression model. High levels of physical activity (OR: 1.607, 95% CI:
1.245-2.074, P < 0.001) were associated with self-rated 'good health' across the
cohort as a whole. All cities except Iasi showed a positive association between
high levels of physical activity and good health. This was significant in four
cases: Amsterdam, Cardiff, Greater Manchester and Merseyside ( P = 0.035, 0.016,
0.010 and 0.049, respectively). Only 13.3% of the cohort met the current WHO
physical activity level recommendations. High levels of physical activity are
positively associated with self-rated 'good health' status in European
adolescents. Alarming levels of physical inactivity make it a priority to
encourage greater engagement in physical activity. Promotion of physical activity
should be specifically tailored to each urban area.
PMID- 28402408
TI - Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic
Exposure: A Randomized Controlled Trial.
AB - Background: Antibiotic exposure can alter the gut microbiome. We evaluate the
effects of azithromycin on the gut microbiome diversity of children from an
antibiotic-naive community in Niger. Methods: A population-based sample of 80
children aged 1-60 months in the Dosso region of Niger was randomized to receive
a single dose of either oral azithromycin or placebo. Fecal samples were
collected immediately before treatment and 5 days after treatment for 16S rRNA
gene sequencing. The prespecified outcome was alpha-diversity (inverse Simpson's
alpha-diversity index), with secondary outcomes of beta and gamma Simpson's and
Shannon's diversities. Results: At 5 days after treatment, 40 children aged 1-60
months were analyzed in the azithromycin-treated group and 40 children in the
placebo-treated group. Diversity of the gut microbiome was significantly lower in
the treated group (inverse Simpson's alpha-diversity, 5.03; 95% confidence
interval [CI], 4.08-6.14) than in the placebo group (6.91; 95% CI, 5.82-8.21; P =
.03). Similarly, the Shannon's alpha-diversity was lower in the treated group
(10.60; 95% CI, 8.82-12.36) than the placebo group (15.42; 95% CI, 13.24-17.80; P
= .004). Simpson's community-level (gamma) diversity decreased with azithromycin
exposure from 17.72 (95% CI, 13.80-20.21) to 10.10 (95% CI, 7.80-11.40; P =
.00008), although beta-diversity was not significantly reduced (2.56, 95% CI,
1.88-3.12; to 2.01, 95% CI, 1.46-2.51; P = .26). Conclusions: Oral administration
of azithromycin definitively decreases the diversity of the gut microbiome of
children in an antibiotic-naive community. Clinical Trials Registration:
NCT02048007.
PMID- 28402411
TI - Impact of acute hypertension transients on diastolic function in patients with
heart failure with preserved ejection fraction.
AB - Aim: To address the mechanisms responsible for the increase in LV filling
pressures induced by acute hypertension transients in patients with heart failure
with preserved ejection fraction (HFpEF). Methods and results: Multiple-beat
pressure-volume loops were recorded during inferior vena cava occlusion in 39
HFpEF patients and 20 controls during handgrip and atrial pacing. We measured the
contribution of relaxation, elastic recoil, and stiffness to instantaneous
diastolic pressure using a novel processing method. Fibrosis was quantified from
endomyocardial biopsies. HFpEF patients showed higher diastolic pressures and
stiffness constant than controls (P < 0.05 for all). As opposed to controls, all
intrinsic global diastolic properties were sensitive to acute changes in systolic
pressure in the HFpEF group. In fact, the stiffness constant increased by more
than 50% during handgrip in HFpEF patients (P < 0.05), tightly related to changes
in systolic pressure (fixed-effect = 0.26 mm Hg per mm Hg [95% CI = 0.15-0.37]; P
< 0.0001). Incomplete relaxation contributed to increasing pressure before atrial
contraction, but changes in end-diastolic pressure was mostly caused by the
increase in stiffness. The degree of pressure-sensitivity of stiffness correlated
with myocardial collagen volume and crosslinking (R = 0.40 to 0.82 for all).
Conclusion: Acute chamber stiffening is the main mechanism responsible for rising
late-diastolic pressures when HFpEF patients undergo hypertension transients.
This stiffening behaviour is related to impaired dynamic systolic-diastolic
interactions and correlates with matrix remodelling. Ventricular-vascular
relationships are a promising target in HFpEF and should be taken into account
when assessing diastolic function.
PMID- 28402412
TI - Effects of neutral salts and pH on the activity and stability of human RNase H2.
AB - Ribonuclease H (RNase H) specifically degrades the RNA of RNA/DNA hybrid. Recent
study has shown that a single ribonucleotide is embedded in DNA double strand at
every few thousand base pairs in human genome, and human RNase H2 is involved in
its removal. Here, we examined the effects of neutral salts and pH on the
activity and stability of human RNase H2. NaCl, KCl, RbCl and NaBr increased the
activity to 170-390% at 10-60 mM, while LiCl, LiBr and CsCl inhibited it,
suggesting that species of cation, but not anion, is responsible for the effect
on activity. NaCl and KCl increased the stability by decreasing the first-order
rate constant of the inactivation to 50-60% at 60-80 mM. The activity at 25-35
degrees C exhibited a narrow bell-shaped pH-dependence with the acidic and
alkaline pKe (pKe1 and pKe2) values of 7.3 - 7.6 and 8.1 - 8.8, respectively.
Enthalpy changes (DeltaH degrees ) of deprotonation were 5 +/- 21 kJ mol-1 for
pKe1 and 68 +/- 25 kJ mol-1 for pKe2. These results suggest that the ionizable
groups responsible for pKe1 may be two out of Asp34, Glu35 and Asp141 of DEDD
motif, and that for pKe2 may be Lys69 of DSK motif.
PMID- 28402413
TI - Regulation of heat-shock genes in bacteria: from signal sensing to gene
expression output.
AB - The heat-shock response is a mechanism of cellular protection against sudden
adverse environmental growth conditions and results in the prompt production of
various heat-shock proteins. In bacteria, specific sensory biomolecules sense
temperature fluctuations and transduce intercellular signals that coordinate gene
expression outputs. Sensory biomolecules, also known as thermosensors, include
nucleic acids (DNA or RNA) and proteins. Once a stress signal is perceived, it is
transduced to invoke specific molecular mechanisms controlling transcription of
genes coding for heat-shock proteins. Transcriptional regulation of heat-shock
genes can be under either positive or negative control mediated by dedicated
regulatory proteins. Positive regulation exploits specific alternative sigma
factors to redirect the RNA polymerase enzyme to a subset of selected promoters,
while negative regulation is mediated by transcriptional repressors.
Interestingly, while various bacteria adopt either exclusively positive or
negative mechanisms, in some microorganisms these two opposite strategies
coexist, establishing complex networks regulating heat-shock genes. Here, we
comprehensively summarize molecular mechanisms that microorganisms have adopted
to finely control transcription of heat-shock genes.
PMID- 28402414
TI - Inter-sectoral Transfer of the Food for Life Settings Framework in England.
AB - Organisational settings such as schools, workplaces and hospitals are well
recognised as key environments for health promotion. Whilst there is extensive
literature on specific types of settings, little empirical research has
investigated the transfer of frameworks between sectors. This study analyses Food
for Life, an England-wide healthy and sustainable food programme that evolved in
schools and is being adapted for children's centres, universities, care homes,
and hospital settings. Following a case study design, we interviewed 85
stakeholders in nine settings. Food for Life's systemic framework of 'food
education, skills and experience' 'food and catering quality', 'community and
partnerships' and 'leadership' carried salience in all types of settings. These
were perceived to act both as principles and operational priorities for driving
systemic change. However, each setting type differed in terms of the mix of
facilitating factors and appropriate indicators for change. Barriers in common
included the level of culture-shift required, cost perceptions and organisational
complexity. For settings based health promotion practice, this study points to
the importance of 'frame-working' (the systematic activity of scoping and
categorising the field of change) alongside the development and application of
benchmarks to stimulate change. These processes are critical in the transfer of
learning from between sectors in a form that balances commonality with sufficient
flexibility to adapt to specific settings. Synergy between types of settings is
an under-recognised, but critical, part of action to address complex issues such
as those emerging from the intersection between food, health and sustainability.
PMID- 28402415
TI - Single versus repeat doses of misoprostol for treatment of early pregnancy loss-a
randomized clinical trial.
AB - STUDY QUESTION: Does repeat administration of misoprostol for early pregnancy
loss increase the treatment success rate? SUMMARY ANSWER: Repeat administration
of misoprostol does not increase the treatment success rate, and is associated
with more analgesics use. WHAT IS KNOWN ALREADY: Misoprostol reduces the need for
surgical evacuation and shortens the time to complete expulsion in patients with
early pregnancy loss. However, the impact of repeat doses of misoprostol is not
clear. STUDY DESIGN, SIZE, DURATION: A randomized clinical trial was conducted in
a single tertiary hospital, recruiting women with early pregnancy loss (<12
weeks), seeking medical treatment, between August 2015 and June 2016. A sample
size of 160 patients was sufficient to detect a 30% decrease in treatment
success. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants received 800 MUg
of misoprostol vaginally on Day 1, and were then randomly assigned into two
groups: Patients in the single-dose group were evaluated on Day 8. Patients in
the repeat-dose group were evaluated on Day 4, when they were given a repeat dose
if required, and scheduled for re-evaluation on Day 8. If complete expulsion was
not achieved on Day 8 (endometrial thickness >15 mm or the presence of
gestational sac on transvaginal sonography), participants underwent surgical
evacuation. The primary outcome was treatment success, defined as no need for
surgical intervention up to Day 8. MAIN RESULTS AND THE ROLE OF CHANCE: Final
analysis included 87 participants in the single-dose group and 84 participants in
the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment
succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in
the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the
repeat-dose group reported more use of over the counter analgesics (82.1% versus
69.0%, P = 0.04). LIMITATIONS, REASONS FOR CAUTION: The study was not blinded and
our definition of complete expulsion may be debated. Follow-up time was not equal
in all participants, since some had a complete expulsion on Day 4 and some
underwent emergent D&C before Day 8. This, however, should not affect the primary
outcome. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a single
dose protocol is superior to a repeat-dose protocol due to a comparable success
rate and more favorable outcomes regarding the need for analgesic drugs. STUDY
FUNDING/COMPETING INTEREST(S): We did not receive funding for this study and we
declare no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
(NCT02515604). TRIAL REGISTRATION DATE: 2 August 2015. DATE OF FIRST PATIENT'S
ENROLMENT: 19 August 2015.
PMID- 28402416
TI - ReGaTE: Registration of Galaxy Tools in Elixir.
AB - Background: Bioinformaticians routinely use multiple software tools and data
sources in their day-to-day work and have been guided in their choices by a
number of cataloguing initiatives. The ELIXIR Tools and Data Services Registry
(bio.tools) aims to provide a central information point, independent of any
specific scientific scope within bioinformatics or technological implementation.
Meanwhile, efforts to integrate bioinformatics software in workbench and workflow
environments have accelerated to enable the design, automation, and
reproducibility of bioinformatics experiments. One such popular environment is
the Galaxy framework, with currently more than 80 publicly available Galaxy
servers around the world. In the context of a generic registry for bioinformatics
software, such as bio.tools, Galaxy instances constitute a major source of
valuable content. Yet there has been, to date, no convenient mechanism to
register such services en masse. We present ReGaTE (Registration of Galaxy Tools
in Elixir), a software utility that automates the process of registering the
services available in a Galaxy instance. This utility uses the BioBlend
application program interface to extract service metadata from a Galaxy server,
enhance the metadata with the scientific information required by bio.tools, and
push it to the registry. ReGaTE provides a fast and convenient way to publish
Galaxy services in bio.tools. By doing so, service providers may increase the
visibility of their services while enriching the software discovery function that
bio.tools provides for its users. The source code of ReGaTE is freely available
on Github at https://github.com/C3BI-pasteur-fr/ReGaTE .
PMID- 28402417
TI - Grandmaternal smoke exposure reduces female fertility in a murine model, with
great-grandmaternal smoke exposure unlikely to have an effect.
AB - STUDY QUESTION: What effect does multigenerational (F2) and transgenerational
(F3) cigarette smoke exposure have on female fertility in mice? SUMMARY ANSWER:
Cigarette smoking has a multigenerational effect on female fertility. WHAT IS
KNOWN ALREADY: It has been well established that cigarette smoking decreases
female fertility. Furthermore, a growing body of evidence suggests that smoking
during pregnancy decreases the fertility of daughters and increases cancer and
asthma incidence in grandchildren and great-grandchildren. STUDY DESIGN, SIZE,
DURATION: Six-week-old C57BL/6 female mice were exposed nasally to cigarette
smoke or room air (controls) for 5 weeks prior to being housed with males.
Females continued to be exposed to smoke throughout pregnancy and lactation until
pups were weaned. A subset of F1 female pups born to these smoke and non-smoke
exposed females were bred to create the F2 grandmaternal exposed generation
(multigenerational). Finally, a subset of F2 females were bred to create the F3
great-grandmaternal exposed generation (transgenerational). The reproductive
health of F2 and F3 females was examined at 8 weeks and 9 months.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian and oocyte quality was examined
in smoke exposed and control animals. A small-scale fertility trial was performed
before ovarian changes were examined using ovarian histology and
immunofluorescence and/or immunoblotting analysis of markers of apoptosis (TUNEL)
and proliferation (proliferating cell nuclear antigen (PCNA) and anti-Mullerian
hormone (AMH)). Oocyte quality was examined using immunocytochemistry to analyze
the metaphase II spindle and ploidy status. Parthenogenetic activation of oocytes
was used to investigate meiosis II timing and preimplantation embryo development.
Finally, diestrus hormone serum levels (FSH and LH) were quantified. MAIN RESULTS
AND THE ROLE OF CHANCE: F2 smoke exposed females had no detectable change in
ovarian follicle quality at 8 weeks, although by 9 months ovarian somatic cell
proliferation was reduced (P = 0.0197) compared with non-smoke exposed control.
Further investigation revealed changes between control and smoke exposed F2
oocyte quality, including altered meiosis II timing at 8 weeks (P = 0.0337) and
decreased spindle pole to pole length at 9 months (P = 0.0109). However, no
change in preimplantation embryo development was observed following
parthenogenetic activation. The most noticeable effect of cigarette smoke
exposure was related to the subfertility of F2 females; F2 smoke exposed females
displayed significantly increased time to conception (P = 0.0042) and
significantly increased lag time between pregnancies (P = 0.0274) compared with
non-smoke exposed F2 females. Conversely, F3 smoke exposed females displayed
negligible oocyte and follicle changes up to 9 months of age, and normal
preimplantation embryo development. LARGE SCALE DATA: None. LIMITATIONS, REASONS
FOR CAUTION: This study focused solely on a mouse model of cigarette smoke
exposure to simulate human exposure. WIDER IMPLICATIONS OF THE FINDINGS: Our
results demonstrate that grandmaternal cigarette smoke exposure reduces female
fertility in mice, highlighting the clinical need to promote cessation of
cigarette smoking in pregnant women. STUDY FUNDING/COMPETING INTEREST(S): This
study was funded by the Australian Research Council, National Health and Medical
Research Council, Hunter Medical Research Institute, Newcastle Permanent Building
Society Charitable Trust, and the University of Newcastle Priory Research Centers
in Chemical Biology, Healthy Lungs and Grow Up Well. The authors declare no
conflict of interest.
PMID- 28402418
TI - An alternative cardiopulmonary bypass strategy for intracaval baffle repair of
scimitar syndrome.
AB - Intracaval buffle repair of scimitar syndrome is classically performed under deep
hypothermic circulatory arrest or using low-flow modalities of cardiopulmonary
bypass with peripheral cannulation. We propose an alternative perfusion approach
to the procedure using total intrapericardial cannulation under full-flow
normothermic cardiopulmonary bypass.
PMID- 28402419
TI - A Systematic Review of Sexual Assaults in Nursing Homes.
AB - Purpose of the Study: The dramatic growth in the older adults (65 years+) has
created an equivalent increase in the number of nursing home (NH) residents. NH
residents often lack physical and cognitive abilities, making them particularly
vulnerable to assault. Although sexual assault is among one of the most shocking
types of assault, it is also the least acknowledged, detected, and reported type
of assault against NH residents. This systematic review examines
victim/perpetrator sociodemographic and relationship characteristics as well as
the forensic characteristics of sexual assaults occurring in NH. Design and
Methods: A 7 database systematic search of studies published between January 1,
1949 and October 26, 2015 was conducted that examined sexual assaults in NH.
Articles reporting on sexual assault in NH and other institutional settings were
eligible. Community-dwelling populations and studies not describing sexual
assault or physical aspects of sexual assault were excluded. Sexual assault was
not restricted to a single definition, study method, or country. Results: Fifteen
studies met inclusion criteria. Sexual assault was the least reported type of
assault in NH. Victims of sexual assault were likely to be females with cognitive
or physical impairments. Perpetrators were likely to be male residents, although
staff members were also substantiated. Forensic characteristics and investigative
data were limited. Study limitation included inconsistencies between study
purposes and small sample sizes. Implications: This review highlights a gap in
knowledge regarding sexual assaults in NH and demonstrates a need for better
staff training in detecting, examining, and managing sexual assaults in NH.
PMID- 28402421
TI - Changes over time in the health and functioning of older people moving into care
homes: analysis of data from the English Longitudinal Study of Ageing.
AB - Background: the number of people requiring care home support is projected to rise
in future years, but little information is available on the needs of new care
home residents. Objective: to measure the health and functioning of people moving
into care homes and how they have changed between 2002 and 2015. Setting: English
Longitudinal Study of Ageing. Participants: two hundred fifty-four of the 313
(1.99%) individuals who moved from the community into a care home, and were
interviewed in the survey wave prior to entry. Main outcome measures: changes
over time for number of health conditions and functional deficits (deficits in
activities of daily living (ADL), and instrumental ADLs (IADLs)), assessed in the
survey wave prior to admission. Results: over time there were significant
increases in the total number of health conditions and functional deficits
amongst soon to be care home entrants (P = 0.0011), the proportion with high
blood pressure (OR 1.37, 95% CI: 1.17-1.62, P < 0.0001), memory problems (OR
1.33, 95% CI: 1.11-1.61, P = 0.0021) or total number of IADL deficits (P =
0.008). Non-significant increases were observed in the proportion of care home
entrants with cancer (OR 1.23, 95% CI: 0.93-1.65, P = 0.15), lung disease (OR
1.21, 95% CI: 0.85-1.75), heart disease (OR 1.12, 95% CI: 0.95-1.30) and
arthritis (OR 1.11, 95% CI: 0.95-1.30). Stroke and ADL deficits did not increase.
No differential ageing effect was observed. Conclusions: the support needs of
care home entrants in England appear to be increasing over time. This has
important implications for the provision and funding of care home places and
community services.
PMID- 28402422
TI - Introduction and assessment of orthognathic information clinic.
AB - Background/Objectives: Orthognathic treatment is routine practice to rehabilitate
severe malocclusions and dentofacial deformities. Because orthognathic treatment
is elective, patient's involvement in deciding whether to proceed with treatment
is vital. Interaction and communication between patient and treating team plays a
key role in achieving post-treatment satisfaction. To achieve satisfaction, an
orthognathic 'information clinic' for prospective orthognathic patients was
established at Oral and Maxillofacial Unit, Tampere University Hospital, Finland.
'Information clinic' includes short talks with power-point presentation given by
orthodontist, oral hygienist, oral and maxillofacial surgeon, psychologist, and
previous patient. Aim of the study was to set up an 'information clinic' and,
more specifically, 1. to assess patients' opinions on the 'clinic' during pilot
phase (2013-14) and 2. to analyse general statistics during the first 3 years
(2013-16). Methods: During the pilot phase, patient opinions, based on voluntary
questionnaire, were obtained from 85 people. General data were collected for the
clinics run in 2013-16. Results: Seventy-two per cent of respondents reported the
information provided to help in their decision-making to proceed/not proceed with
treatment. Majority considered the information about the surgical aspects and
meeting patient who had undergone orthognathic treatment to be the most important
part of the clinic. Between March 2013 and 2016, 290 prospective orthognathic
patients were invited to 29 'information clinics'. One hundred and ninety-four
patients attended, of whom 137 were female and 57 male (age range 15-67 years).
Conclusions: The questionnaire and verbal feedback from the patients was
positive; hence, the 'information clinic' is now offered as a routine process to
all prospective orthognathic patients in our clinic.
PMID- 28402420
TI - The effect of health insurance and health facility-upgrades on hospital
deliveries in rural Nigeria: a controlled interrupted time-series study.
AB - Background: Access to quality obstetric care is considered essential to reducing
maternal and new-born mortality. We evaluated the effect of the introduction of a
multifaceted voluntary health insurance programme on hospital deliveries in rural
Nigeria. Methods: We used an interrupted time-series design, including a control
group. The intervention consisted of providing voluntary health insurance
covering primary and secondary healthcare, including antenatal and obstetric
care, combined with improving the quality of healthcare facilities. We compared
changes in hospital deliveries from 1 May 2005 to 30 April 2013 between the
programme area and control area in a difference-in-differences analysis with
multiple time periods, adjusting for observed confounders. Data were collected
through household surveys. Eligible households ( n = 1500) were selected from a
stratified probability sample of enumeration areas. All deliveries during the 4
year baseline period ( n = 460) and 4-year follow-up period ( n = 380) were
included. Findings: Insurance coverage increased from 0% before the insurance was
introduced to 70.2% in April 2013 in the programme area. In the control area
insurance coverage remained 0% between May 2005 and April 2013. Although hospital
deliveries followed a common stable trend over the 4 pre-programme years ( P =
0.89), the increase in hospital deliveries during the 4-year follow-up period in
the programme area was 29.3 percentage points (95% CI: 16.1 to 42.6; P < 0.001)
greater than the change in the control area (intention-to-treat impact),
corresponding to a relative increase in hospital deliveries of 62%. Women who did
not enroll in health insurance but who could make use of the upgraded care
delivered significantly more often in a hospital during the follow-up period than
women living in the control area ( P = 0.04). Conclusions: Voluntary health
insurance combined with quality healthcare services is highly effective in
increasing hospital deliveries in rural Nigeria, by improving access to
healthcare for insured and uninsured women in the programme area.
PMID- 28402424
TI - Response to the comment: Variable selection should be blinded to the outcome.
PMID- 28402423
TI - DeCoSTAR: Reconstructing the Ancestral Organization of Genes or Genomes Using
Reconciled Phylogenies.
AB - Availability: http://pbil.univ-lyon1.fr/software/DeCoSTAR (Last accessed April
24, 2017).
PMID- 28402425
TI - Therapeutic approaches for Long QT syndrome type 3: an update.
PMID- 28402426
TI - Commentary on: CD30+ T Cells in Late Seroma May Not Be Diagnostic of Breast
Implant-Associated Anaplastic Large Cell Lymphoma.
PMID- 28402428
TI - Bayesian Mapping Reveals That Attention Boosts Neural Responses to Predicted and
Unpredicted Stimuli.
AB - Predictive coding posits that the human brain continually monitors the
environment for regularities and detects inconsistencies. It is unclear, however,
what effect attention has on expectation processes, as there have been relatively
few studies and the results of these have yielded contradictory findings. Here,
we employed Bayesian model comparison to adjudicate between 2 alternative
computational models. The "Opposition" model states that attention boosts neural
responses equally to predicted and unpredicted stimuli, whereas the "Interaction"
model assumes that attentional boosting of neural signals depends on the level of
predictability. We designed a novel, audiospatial attention task that
orthogonally manipulated attention and prediction by playing oddball sequences in
either the attended or unattended ear. We observed sensory prediction error
responses, with electroencephalography, across all attentional manipulations.
Crucially, posterior probability maps revealed that, overall, the Opposition
model better explained scalp and source data, suggesting that attention boosts
responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic
Causal Modeling showed that these Opposition effects were expressed in plastic
changes within the mismatch negativity network. Our findings provide empirical
evidence for a computational model of the opposing interplay of attention and
expectation in the brain.
PMID- 28402427
TI - BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis
exposure and host susceptibility interaction.
AB - Cannabis abuse in adolescence is associated with increased risk of psychotic
disorders. Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive
component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver
for major mental illness by influencing neurodevelopmental processes. Here,
utilizing a unique mouse model based on host (DISC1) X environment (THC
administration) interaction, we aimed at studying the pathobiological basis
through which THC exposure elicits psychiatric manifestations. Wild-Type and
dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or
vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests
were conducted to assess exploratory activity (open field test, light-dark box
test) and cognitive function (novel object recognition test).
Electrophysiological effect of THC was evaluated using acute hippocampal slices,
and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor
(BDNF) protein levels were measured. Our results indicate that THC exposure
elicits deficits in exploratory activity and recognition memory, together with
reduced short-term synaptic facilitation and loss of BDNF surge in the
hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF
in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in
recognition memory. The results of this study imply that induction of BDNF
following adolescence THC exposure may serve as a homeostatic response geared to
maintain proper cognitive function against exogenous insult. The BDNF surge in
response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1
may be a useful probe to identify biological cascades involved in the
neurochemical, electrophysiological, and behavioral effects of cannabis related
psychiatric manifestations.
PMID- 28402430
TI - ST segment depression on 24-hour electrocardiography predicts incident atrial
fibrillation in two population-based cohorts.
AB - Aims: ST-depression at 24hECG has not been studied in relation to atrial
fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was
associated with incident AF in two Swedish population-based cohorts - a sub
cohort of the Malmo Diet and Cancer study (MDCS), and the cohort 'Men born in
1914', and to determine whether 24hECG could be used to predict AF development.
Methods and results: There were 378 acceptable 24hECG recordings in the MDCS
(mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in
1914' (mean age 68.8 years). Incidence of AF was monitored using national
registers of hospitalizations and outpatient visits in Sweden. Mean follow-up +/-
SD (cumulative incidence) was 10.4 +/- 2 years (11.3%) in MDCS, and 10.9 +/- 4
years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated
with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28
(1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood
pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR
(in MDCS)]. AF incidence was substantially lower in individuals who had neither
ST-depressions or high supraventricular activity (SVA, negative predictive value
0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men
and women. Conclusion: ST-depression at 24h-ECG is independently associated with
incident AF, and incidence is substantially lower in individuals with neither ST
depression or high SVA. 24hECG can be used not only to diagnose AF but also to
identify individuals at high and low AF risk.
PMID- 28402429
TI - A high quality Arabidopsis transcriptome for accurate transcript-level analysis
of alternative splicing.
AB - Alternative splicing generates multiple transcript and protein isoforms from the
same gene and thus is important in gene expression regulation. To date, RNA
sequencing (RNA-seq) is the standard method for quantifying changes in
alternative splicing on a genome-wide scale. Understanding the current
limitations of RNA-seq is crucial for reliable analysis and the lack of high
quality, comprehensive transcriptomes for most species, including model organisms
such as Arabidopsis, is a major constraint in accurate quantification of
transcript isoforms. To address this, we designed a novel pipeline with stringent
filters and assembled a comprehensive Reference Transcript Dataset for
Arabidopsis (AtRTD2) containing 82,190 non-redundant transcripts from 34 212
genes. Extensive experimental validation showed that AtRTD2 and its modified
version, AtRTD2-QUASI, for use in Quantification of Alternatively Spliced
Isoforms, outperform other available transcriptomes in RNA-seq analysis. This
strategy can be implemented in other species to build a pipeline for transcript
level expression and alternative splicing analyses.
PMID- 28402431
TI - Geographic Disparities in Access to Syringe Services Programs Among Young Persons
With Hepatitis C Virus Infection in the United States.
AB - Using commercial laboratory data, we found 80% of 29382 young persons currently
infected with hepatitis C virus lived >10 miles from a syringe services program.
The median distance was 37 miles, with greater distances in rural areas and
Southern and Midwestern states. Strategies to improve access to preventive
services are warranted.
PMID- 28402432
TI - Educational outcomes of a medical physicist program over the past 10 years in
Japan.
AB - The promotion plan for the Platform of Human Resource Development for Cancer
(Ganpro) was initiated by the Ministry of Education, Culture, Sports, Science and
Technology of Japan in 2007, establishing a curriculum for medical physicists. In
this study, we surveyed the educational outcomes of the medical physicist program
over the past 10 years since the initiation of Ganpro. The Japan Society of
Medical Physics mailing list was used to announce this survey. The questionnaire
was created by members of the Japanese Board for Medical Physicist Qualification,
and was intended for the collection of information regarding the characteristics
and career paths of medical physics students. Students who participated in the
medical physics program from 2007 to 2016 were enrolled. Thirty-one universities
(17 accredited and 14 non-accredited) were represented in the survey. In total,
491, 105 and 6 students were enrolled in the Master's, Doctorate and Residency
programs, respectively. Most students held a Bachelor's degree in radiological
technology (Master's program, 87%; Doctorate program, 72%). A large number of
students with a Master's degree worked as radiological technologists (67%),
whereas only 9% (n = 32) worked as medical physicists. In contrast, 53% (n = 28)
of the students with a Doctorate degree worked as medical physicists. In total,
602 students (from 31 universities) completed the survey. Overall, although the
number of the graduates who worked as medical physicists was small, this number
increased annually. It thus seems that medical institutions in Japan are
recognizing the necessity of licensed medical physicists in the radiotherapy
community.
PMID- 28402433
TI - H3K4 demethylase KDM5B regulates global dynamics of transcription elongation and
alternative splicing in embryonic stem cells.
AB - Epigenetic regulation of chromatin plays a critical role in controlling embryonic
stem (ES) cell self-renewal and pluripotency. However, the roles of histone
demethylases and activating histone modifications such as trimethylated histone 3
lysine 4 (H3K4me3) in transcriptional events such as RNA polymerase II (RNAPII)
elongation and alternative splicing are largely unknown. In this study, we show
that KDM5B, which demethylates H3K4me3, plays an integral role in regulating
RNAPII occupancy, transcriptional initiation and elongation, and alternative
splicing events in ES cells. Depletion of KDM5B leads to altered RNAPII promoter
occupancy, and decreased RNAPII initiation and elongation rates at active genes
and at genes marked with broad H3K4me3 domains. Moreover, our results demonstrate
that spreading of H3K4me3 from promoter to gene body regions, which is mediated
by depletion of KDM5B, modulates RNAPII elongation rates and RNA splicing in ES
cells. We further show that KDM5B is enriched nearby alternatively spliced exons,
and depletion of KDM5B leads to altered levels of H3K4 methylation in
alternatively spliced exon regions, which is accompanied by differential
expression of these alternatively splice exons. Altogether, our data indicate an
epigenetic role for KDM5B in regulating RNAPII elongation and alternative
splicing, which may support the diverse mRNA repertoire in ES cells.
PMID- 28402434
TI - Healthy Lifestyle and Blood Pressure Variability in Young Adults.
AB - BACKGROUND: The aim of this study was to assess the relationships between healthy
lifestyle metrics and blood pressure variability (BPV) in young and healthy
adults. METHODS: A population-based sample of 1,999 individuals aged 25-41 years
was investigated. A lifestyle-score from 0 (most unhealthy) to 7 (most healthy)
was calculated by giving one point for each of the following components: never
smoking cigarettes, adhering to a healthy diet, performing moderate or intense
physical activity, having a body mass index <25 kg/m2, a total cholesterol <200
mg/dl, a glycated hemoglobin <5.7%, or a conventional BP <120/80 mm Hg.
Standardized ambulatory 24-hour BP measurements were obtained in all individuals.
BPV was defined as the SD of all individual ambulatory BP recordings. We
constructed multivariable linear regression models to assess the relationships
between the lifestyle-score and BPV. None of the results were adjusted for
multiple testing. RESULTS: Median age was 37 years and 46.8% were men. With
increasing lifestyle-score, systolic and diastolic BPV is decreasing linearly (P
for trend <0.0001), even after multivariable adjustment. Per 1-point increase in
lifestyle-score, the beta-coefficient (95% confidence interval) for systolic and
diastolic 24-hour BPV was -0.03 (-0.03; -0.02) and -0.04 (-0.05; -0.03),
respectively, both P for trend <0.0001. These relationships were attenuated but
remained statistically significant after additional adjustment for mean
individual BP. CONCLUSION: In this study of young and healthy adults, adopting a
healthy lifestyle was associated with a lower BPV. These associations were
independent of mean BP levels.
PMID- 28402435
TI - Comparative Effect of Three Neurotoxic Insecticides With Different Modes of
Action on Adult Males and Females of Three Tortricid Moth Pests.
AB - Insecticides are the dominant pest management method in fruit and vegetable crops
worldwide owing to their quick effect, low cost, and relatively easy application,
but they bear negative effects on human health and the environment. Insecticide
mode of action (MoA), target species, and sex are variables that could affect
insecticide-induced mortality. We recorded the mortality caused by three
neurotoxic insecticides with different modes of action (chlorpyrifos
[organophosphate, acetylcholinesterase inhibitor], lambda-cyhalothrin
[pyrethroid, sodium channel modulator], and thiacloprid [neonicotinoid, nicotinic
acetylcholinesterase receptor agonist]) applied topically to adult males and
females of three economically important tortricid species [Cydia pomonella (L.),
Grapholita molesta (Busck), and Lobesia botrana (Denis & Schiffermuller)] that
strongly depend on insecticide use for their control. Concentration and dose
mortality curves were recorded at 24 and 48 h postapplication. Large mortality
differences between insecticides (maximum 7,800-fold for LD50) were followed by
much lower, yet important, differences between species (maximum 115-fold), and
sexes (maximum 41.5-fold). Significant interactions between the three factors
indicate that they are not independent from each other. Interestingly, with the
organophosphate chlorpyrifos, males of the three species were less susceptible
than females, which was unexpected, as females are larger than males. Higher
female sensitivity to organophosphates has been reported previously but only in
G. molesta, not in other moth species. Our results highlight the importance of
taking into account sex in dose-mortality studies with adult moths.
PMID- 28402436
TI - Repellency of 29 Synthetic and Natural Commercial Topical Insect Repellents
Against Aedes aegypti (Diptera: Culicidae) in Central Mexico.
AB - In Mexico, the use of repellents to prevent insects from landing and biting is a
common practice. However, variation in the efficiency of natural and synthetic
repellents has been observed. In this study, we evaluated the repellency and
protection time of 16 synthetic and 13 natural-based commercial products against
Aedes aegypti (L.) from an endemic dengue area (Jojutla, Morelos) in Central
Mexico. The "arm exposure" cage test was used to assess the efficacy of the
repellents. Tests were conducted by three adult volunteers. Results showed that
DEET (N, N-Diethyl-3-methylbenzamide) repellents provided the highest protection
and duration times against Ae. aegypti. However, low repellency and short-time
protection was observed (when compared with the manufacturers' protection times).
Natural-based products did not repel (either landing or biting) mosquitoes for
>30 min. These results show that most of the repellent products did not provide
satisfactory levels of personal protection against mosquito bites. Frequent
reapplication of repellents (synthetic and natural-based) may compensate for
their short duration of action. Repellent efficacy data must be integrated into
the decision-making process for an optimal response to the local (or specific
region) situation.
PMID- 28402437
TI - Policy ideals and everyday politics in the Partnership for Maternal, Newborn and
Child Health-the role of ethnography.
PMID- 28402438
TI - Cardiac investigation for prognosis in coronary artery disease: where negative is
positive.
PMID- 28402439
TI - Chromodomain protein CDYL is required for transmission/restoration of repressive
histone marks.
AB - Faithful transmission or restoration of epigenetic information such as repressive
histone modifications through generations is critical for the maintenance of cell
identity. We report here that chromodomain Y-like protein (CDYL), a chromodomain
containing transcription corepressor, is physically associated with chromatin
assembly factor 1 (CAF-1) and the replicative helicase MCM complex. We showed
that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition
during DNA replication. We demonstrated that CDYL recruits histone-modifying
enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of
H3K9me2/3 and H3K27me2/3 on newly deposited histone H3. Significantly, depletion
of CDYL impedes early S phase progression and sensitizes cells to DNA damage. Our
data indicate that CDYL plays an important role in the transmission/restoration
of repressive histone marks, thereby preserving the epigenetic landscape for the
maintenance of cell identity.
PMID- 28402441
TI - Mining prokaryotes for antimicrobial compounds: from diversity to function.
AB - The bacterial kingdom provides a major source of antimicrobials that can either
be directly applied or used as scaffolds to further improve their functionality
in the host. The rapidly increasing amount of bacterial genomic, metabolomic and
transcriptomic data offers unique opportunities to apply a variety of approaches
to mine for existing and novel antimicrobials. Here, we discuss several powerful
mining approaches to identify novel molecules with antimicrobial activity across
structurally diverse natural products, including ribosomally synthesized and
posttranslationally modified peptides, nonribosomal peptides and polyketides. We
not only discuss the direct mining of genomes based on identification of
biosynthetic gene clusters, but also describe more advanced and integrative
approaches in ecology-based mining, functionality-based mining and mode-of-action
based mining. These efforts are likely to accelerate the discovery and
development of novel antimicrobial drugs.
PMID- 28402440
TI - A Prospective Study of Urinary Prostaglandin E2 Metabolite, Helicobacter pylori
Antibodies, and Gastric Cancer Risk.
AB - Background: Previous studies suggest that a stable end-product of prostaglandin
E2, the urinary metabolite PGE-M, is associated with colorectal cancer, and 1
study of relatively small sample size found an association with gastric cancer
among women. In the present study we further investigate the PGE-M, Helicobacter
pylori, and gastric cancer association. Methods: The present analysis included
359 prospectively ascertained gastric cancer cases and 700 individually matched
controls from the Shanghai Women's and Men's Health Studies. Urinary PGE-M was
measured by a liquid chromatography/tandem mass spectrometric method.
Seropositivity to 15 H. pylori recombinantly expressed fusion proteins was
detected by H. pylori multiplex serology. Results: Adjusting for H. pylori,
increasing PGE-M was associated with higher risk of gastric cancer (quartile 4 vs
1: odds ratio [OR], 1.76 [95% confidence interval {CI}, 1.17-2.66], Ptrend =
.004). This association remained after excluding those diagnosed within 2 years
from sample collection (OR, 1.73 [95% CI, 1.12-2.65], Ptrend = .007). However it
was no longer present among individuals with 10 or more years of follow-up (2-4.9
years: OR, 3.15 [95% CI, 1.11-8.91]; 5-9.9 years: OR, 2.23 [95% CI, 1.22-4.06];
>=10 years: OR, 0.73 [95% CI, .31-1.70]). Compared to H. pylori-negative
individuals with below-median PGE-M levels, H. pylori-positive individuals with
above-median PGE-M levels had a 5-fold increase in the odds of gastric cancer
(OR, 5.08 [95% CI, 2.47-10.43]). Conclusions: In China, higher PGE-M levels may
indicate an increased risk of gastric cancer independent of the risk conferred by
H. pylori infection status, particularly for cancers diagnosed within 10 years of
sample collection.
PMID- 28402442
TI - Risk of heterosexual HIV transmission attributable to sexually transmitted
infections and non-specific genital inflammation in Zambian discordant couples,
1994-2012.
AB - Background: Studies have demonstrated the role of ulcerative and non-ulcerative
sexually transmitted infections (STI) in HIV transmission/acquisition risk; less
is understood about the role of non-specific inflammatory genital abnormalities.
Methods: HIV-discordant heterosexual Zambian couples were enrolled into
longitudinal follow-up (1994-2012). Multivariable models estimated the effect of
genital ulcers and inflammation in both partners on time-to-HIV transmission
within the couple. Population-attributable fractions (PAFs) were calculated.
Results: A total of 207 linked infections in women occurred over 2756 couple
years (7.5/100 CY) and 171 in men over 3216 CY (5.3/100 CY). Incident HIV among
women was associated with a woman's non-STI genital inflammation (adjusted hazard
ratio (aHR) = 1.55; PAF = 8%), bilateral inguinal adenopathy (BIA; aHR = 2.33;
PAF = 8%), genital ulceration (aHR = 2.08; PAF = 7%) and the man's STI genital
inflammation (aHR = 3.33; PAF = 5%), BIA (aHR = 3.35; PAF = 33%) and genital
ulceration (aHR = 1.49; PAF = 9%). Infection among men was associated with a
man's BIA (aHR = 4.11; PAF = 22%) and genital ulceration (aHR = 3.44; PAF = 15%)
as well as with the woman's non-STI genital inflammation (aHR = 1.92; PAF = 13%)
and BIA (aHR = 2.76; PAF = 14%). In HIV-M+F- couples, the man being
uncircumcised. with foreskin smegma. was associated with the woman's
seroconversion (aHR = 3.16) relative to being circumcised. In F+M- couples,
uncircumcised men with BIA had an increased hazard of seroconversion (aHR = 13.03
with smegma and 4.95 without) relative to being circumcised. Self-reporting of
symptoms was low for ulcerative and non-ulcerative STIs. Conclusions: Our
findings confirm the role of STIs and highlight the contribution of non-specific
genital inflammation to both male-to-female and female-to-male HIV
transmission/acquisition risk. Studies are needed to characterize pathogenesis of
non-specific inflammation including inguinal adenopathy. A better understanding
of genital practices could inform interventions.
PMID- 28402443
TI - Effect of radiation-induced endothelial cell injury on platelet regeneration by
megakaryocytes.
AB - Thrombocytopenia is an important cause of hemorrhage and death after radiation
injury, but the pathogenesis of radiation-induced thrombocytopenia has not been
fully characterized. Here, we investigated the influence of radiation-induced
endothelial cell injury on platelet regeneration. We found that human umbilical
vein endothelial cells (HUVECs) underwent a high rate of apoptosis, accompanied
by a significant reduction in the expression of vascular endothelial growth
factor (VEGF) at 96 h after radiation. Subsequent investigations revealed that
radiation injury lowered the ability of HUVECs to attract migrating
megakaryocytes (MKs). Moreover, the adhesion of MKs to HUVECs was markedly
reduced when HUVECs were exposed to radiation, accompanied by a decreased
production of platelets by MKs. In vivo study showed that VEGF treatment
significantly promoted the migration of MKs into the vascular niche and
accelerated platelet recovery in irradiated mice. Our studies demonstrate that
endothelial cell injury contributes to the slow recovery of platelets after
radiation, which provides a deeper insight into the pathogenesis of
thrombocytopenia induced by radiation.
PMID- 28402445
TI - De novo p.T362R mutation in MORC2 causes early onset cerebellar ataxia, axonal
polyneuropathy and nocturnal hypoventilation.
PMID- 28402444
TI - Stepwise assembly of the earliest precursors of large ribosomal subunits in
yeast.
AB - Small ribosomal subunits are co-transcriptionally assembled on the nascent
precursor rRNA in Saccharomyces cerevisiae. It is unknown how the highly
intertwined structure of 60S large ribosomal subunits is initially formed. Here,
we affinity purified and analyzed a series of pre-60S particles assembled in vivo
on plasmid-encoded pre-rRNA fragments of increasing lengths, revealing a
spatiotemporal assembly map for 34 trans-acting assembly factors (AFs), 30
ribosomal proteins and 5S rRNA. The gradual association of AFs and ribosomal
proteins with the pre-rRNA fragments strongly supports that the pre-60S is co
transcriptionally, rather than post-transcriptionally, assembled. The internal
and external transcribed spacers ITS1, ITS2 and 3? ETS in pre-rRNA must be
processed in pre-60S. We show that the processing machineries for ITS1 and ITS2
are primarily recruited by the 5? and 3? halves of pre-27S RNA, respectively.
Nevertheless, processing of both ITS1 and ITS2 requires a complete 25S region.
The 3? ETS plays a minor role in ribosome assembly, but is important for
efficient rRNA processing and ribosome maturation. We also identified a distinct
pre-60S state occurring before ITS2 processing. Our data reveal the elusive co
transcriptional assembly pathway of large ribosomal subunit.
PMID- 28402446
TI - Adiponectin and Its Receptors in Diabetic Kidney Disease: Molecular Mechanisms
and Clinical Potential.
AB - Diabetic kidney disease (DKD) is a major complication for diabetic patients.
Adiponectin is an insulin sensitizer and anti-inflammatory adipokine and is
mainly secreted by adipocytes. Two types of adiponectin receptors, AdipoR1 and
AdipoR2, have been identified. In both type 1 and type 2 diabetes (T2D) patients
with DKD, elevated adiponectin serum levels have been observed, and adiponectin
serum level is a prognostic factor of end-stage renal disease. Renal
insufficiency and tubular injury possibly play a contributory role in increases
in serum and urinary adiponectin levels in diabetic nephropathy by either
increasing biodegradation or elimination of adiponectin in the kidneys, or
enhancing production of adiponectin in adipose tissue. Increases in adiponectin
levels resulted in amelioration of albuminuria, glomerular hypertrophy, and
reduction of inflammatory response in kidney tissue. The renoprotection of
adiponectin is associated with improvement of the endothelial dysfunction,
reduction of oxidative stress, and upregulation of endothelial nitric oxide
synthase expression through activation of adenosine 5'-monophosphate-activated
protein kinase by AdipoR1 and activation of peroxisome proliferator-activated
receptor (PPAR)-alpha signaling pathway by AdipoR2. Several single nucleotide
polymorphisms in the AdipoQ gene, including the promoter, are associated with
increased risk of the development of T2D and DKD. Renin-angiotensin-aldosterone
system blockers, adiponectin receptor agonists, and PPAR agonists (e.g.,
tesaglitazar, thiazolidinediones, fenofibrate), which increase plasma adiponectin
levels and adiponectin receptors expression, may be potential therapeutic drugs
for the treatment of DKD.
PMID- 28402448
TI - Catherine L. Thompson. Patient Expectations: How Economics, Religion, and
Malpractice Shaped Therapeutics in Early America.
PMID- 28402447
TI - Infectious Disease Dynamics Inferred from Genetic Data via Sequential Monte
Carlo.
AB - Genetic sequences from pathogens can provide information about infectious disease
dynamics that may supplement or replace information from other epidemiological
observations. Most currently available methods first estimate phylogenetic trees
from sequence data, then estimate a transmission model conditional on these
phylogenies. Outside limited classes of models, existing methods are unable to
enforce logical consistency between the model of transmission and that underlying
the phylogenetic reconstruction. Such conflicts in assumptions can lead to bias
in the resulting inferences. Here, we develop a general, statistically efficient,
plug-and-play method to jointly estimate both disease transmission and phylogeny
using genetic data and, if desired, other epidemiological observations. This
method explicitly connects the model of transmission and the model of phylogeny
so as to avoid the aforementioned inconsistency. We demonstrate the feasibility
of our approach through simulation and apply it to estimate stage-specific
infectiousness in a subepidemic of human immunodeficiency virus in Detroit,
Michigan. In a supplement, we prove that our approach is a valid sequential Monte
Carlo algorithm. While we focus on how these methods may be applied to population
level models of infectious disease, their scope is more general. These methods
may be applied in other biological systems where one seeks to infer population
dynamics from genetic sequences, and they may also find application for
evolutionary models with phenotypic rather than genotypic data.
PMID- 28402450
TI - Sudden cardiac death in adults with congenital heart disease: does QRS-complex
fragmentation discriminate in structurally abnormal hearts?
AB - Aims: Sudden cardiac death (SCD) causes a large portion of all mortality in adult
congenital heart disease (ACHD) patients. However, identification of high-risk
patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for
SCD in patients with acquired heart disease but data in ACHD patients are
lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in
ACHD patients. Methods and results: From a multicentre cohort of 25 790 ACHD
patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266)
matched by age, gender, congenital defect and (surgical) intervention. fQRS was
defined as >=1 discontinuous deflection in narrow QRS-complexes, and >=2 in wide
QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios
(OR) using univariable and multivariable conditional logistic regression models
correcting for impaired systemic ventricular function, heart failure and QRS
duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years)
and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of
controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently
associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was
tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs.
43% of controls (OR for SCD 2.8, P = 0.03). Conclusions: fQRS was independently
associated with SCD in ACHD patients in a cohort of SCD patients and matched
controls. fQRS may therefore contribute to the decision when evaluating ACHD
patients for primary prevention of SCD.
PMID- 28402451
TI - Right ventricular lead malposition.
PMID- 28402449
TI - Enhancement of trophoblast differentiation and survival by low molecular weight
heparin requires heparin-binding EGF-like growth factor.
AB - STUDY QUESTION: Does low molecular weight heparin (LMWH) require heparin-binding
epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce
extravillous trophoblast differentiation and decrease apoptosis during oxidative
stress? SUMMARY ANSWER: LMWH increased HBEGF expression and secretion, and HBEGF
signaling was required to stimulate trophoblast extravillous differentiation,
increase invasion in vitro and reduce trophoblast apoptosis during oxidative
stress. WHAT IS KNOWN ALREADY: Abnormal trophoblast differentiation and survival
contribute to placental insufficiency syndromes, including preeclampsia and
intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic
state, with unsuccessful transformation of the spiral arteries that reduces
oxygen supply and can produce placental infarction. LMWH improves placental
function by increasing blood flow. Recent data suggest that the actions of LMWH
transcend its anti-coagulative properties, but the molecular mechanism is
unknown. There is evidence that LMWH alters the expression of human HBEGF in
trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF,
itself, is capable of increasing trophoblast survival and invasiveness. STUDY
DESIGN, SIZE, DURATION: First-trimester placental explants and the HTR-8/SVneo
cell line, established using extravillous trophoblast outgrowths from first
trimester villous explants, were treated in vitro with LMWH to examine the
effects on HBEGF signaling and trophoblast function under normal physiological
and pathological conditions. A highly specific antagonist of HBEGF and other
inhibitors of HBEGF downstream signaling were used to determine the relationship
between LMWH treatment and HBEGF. PARTICIPANTS/MATERIALS, SETTING, METHODS:
Placental tissues (n = 5) were obtained with IRB approval and patient consent
from first-trimester terminations. Placental explants and HTR-8/SVneo cells were
cultured on plastic or MatrigelTM and treated with a therapeutic dose of LMWH
(Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine
Kinase (ERBB) inhibitor, anti-ERBB1 or ERBB4 blocking antibodies, or pretreatment
of cells with heparitinase I. Extravillous differentiation was assessed by
immunocytochemistry to determine the relative levels of integrins alpha6beta4 and
alpha1beta1. Trophoblast invasiveness was assessed in villous explants by
measuring outgrowth from villous tips cultured on Matrigel, and by invasion
assays with HTR-8/SVneo cells cultured on Matrigel-coated transwell insert.
Placental explants and HTR-8/SVneo cells were exposed to oxidative stress in a
hypoxia-reoxygenation (H-R) model, measuring cell death by TUNEL assay, caspase 3
cleavage, and BCL-2alpha expression. MAIN RESULTS AND THE ROLE OF CHANCE: LMWH
induced extravillous differentiation, according to trophoblast invasion assays
and integrin (alpha6beta4-alpha1beta1) switching. Treatment with LMWH rescued
cytotrophoblasts and HTR-8/SVneo cells from apoptosis during exposure to
reoxygenation injury, based on TUNEL, caspase 3 cleavage and BCL-2alpha
expression. Experiments using CRM197, ERBB1 and ERBB4 blocking antibodies, pan
ERBB inhibitor and removal of cell surface heparin demonstrated that the effects
of LMWH on trophoblast invasion and survival were dependent upon HBEGF signaling.
LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The primary limitation
of this study was the use of only in vitro experiments. Patient demographics from
elective terminations were not available. WIDER IMPLICATIONS OF THE FINDINGS:
These data provide new insights into the non-coagulation-related aspects of
perinatal LMWH treatment in the management of placental insufficiency disorders.
STUDY FUNDING/COMPETING INTEREST(S): This research was supported by grants from
the National Institutes of Health (HD071408 and HL128628), the March of Dimes,
and the W. K. Kellogg Foundation. There were no conflicts or competing interests.
PMID- 28402452
TI - Prepatellar subcutaneous calcifications in systemic sclerosis.
PMID- 28402453
TI - Medina(r) Embolization Device for the Treatment of Intracranial Aneurysms: Safety
and Angiographic Effectiveness at 6 Months.
AB - BACKGROUND: The Medina Embolization Device (MED) is a new concept device that
combines the design of a detachable coil and the one of an intrasaccular flow
disruption device. OBJECTIVE: To evaluate the feasibility, safety, and 6- to 9-mo
effectiveness of this new device for the treatment of intracranial wide-necked
aneurysms. METHODS: Twelve patients (10 females, mean age = 56 yr) with 13 wide
necked intracranial aneurysms (3 ruptured; 10 unruptured) were treated by means
of the MED from January 2015 to October 2015. In 15% of the cases, MEDs were used
in a standalone fashion; in 85% of the cases, additional regular coils were used.
Adjunctive compliant balloon was used in 4 of 13 cases (31%). Procedure-related
complications were systematically recorded; discharge and 6- to 9-mo follow-up
modified Rankin Scale was assessed. Angiographic follow-up was performed with a
mean delay of 5.5 +/- 1.7 mo. Occlusion rate was evaluated in postprocedure and
at midterm follow-up using the Roy-Raymond scale. RESULTS: The deployment of the
MED was feasible in all cases. No perforation was recorded. One case of
thromboembolic complication was observed in a ruptured anterior communicating
artery aneurysm, without any clinical consequence at follow-up. Grade A occlusion
rate was 61.5% in postprocedure and 83% at 6-mo follow-up. Two cases (17%) of
recanalization were documented angiographically. CONCLUSION: The MED is a new
generation device combining the design of a detachable coil and an intrasaccular
flow disruption device. According to our early experience, this device is safe
and provides a satisfactory occlusion rate at angiographic follow-up of 6 mo.
PMID- 28402454
TI - Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease
Recurrence. A GETECCU Randomised Trial.
AB - Background and Aims: Postoperative recurrence of Crohn's disease [POR-CD] is
almost certain if no prophylaxis is administered. Evidence for optimal treatment
is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and
azathioprine [AZA] in this setting. Methods: We performed a phase 3, 52-week,
multicentre, randomised, superiority study [APPRECIA], in which patients with
ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously
[SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary
endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as
evaluated by a blinded central reader. Results: We recruited 91 patients [median
age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous
resections]. The study drugs were administered to 84 patients. Treatment was
discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was
significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%]
(dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat
analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45
patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61
patients with centrally evaluable images], recurrence was recorded in 8/24
[33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No
statistically significant differences between the groups were found for
recurrence in magnetic resonance images, biological markers of activity, surgical
procedures, or hospital admissions. Conclusions: ADA has not demonstrated a
better efficacy than AZA [both associated with metronidazole] for prophylaxis of
POR-CD in an unselected population, although tolerance to ADA is significantly
better. ClinicalTrials.gov NCT01564823.
PMID- 28402456
TI - Smoking Cessation and the Reduction of Disability Progression in Multiple
Sclerosis: A Cohort Study.
AB - Background: Smoking is associated with a more severe disease course in people
with multiple sclerosis (MS). The magnitude of effect of smoking cessation on MS
progression is unknown. The aim of this study was to quantify the impact of
smoking cessation on reaching MS disability milestones. Aims and Methods: This is
a cross-sectional study with retrospective reports. A comprehensive smoking
questionnaire was sent to 1270 patients with MS registered between 1994 and 2013
in the Nottingham University Hospital MS Clinics database. Demographic and
clinical data were extracted from the clinical database. Cox proportional hazard
regression was used to estimate effects of smoke-free years on the time to
Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0. MS Impact Scale 29
and Patient Determined Disease Steps were used to assess the physical and
psychological impact of smoking. Results: Each "smoke-free year" was associated
with 0.96 (95% confidence interval: 0.95 to 0.97) times decreased risk of
reaching EDSS 4.0 and 0.97 (95% confidence interval: 0.95 to 0.98) times
decreased risk of reaching EDSS 6.0. Nonsmokers showed a significantly lower
level of disability in all the self-reported outcomes compared with current
smokers. Conclusions: The reduction in the risk of disability progression after
smoking cessation is significant and time dependent. The earlier the patients
quit, the stronger the reduction in the risk of reaching disability milestones.
The quantitative estimates of the impact of smoking cessation on reaching
disability milestones in MS can be used in interventional trials. Implications:
This study provides for the first time quantitative estimates of the effects of
smoking cessation in MS, essential for informing smoking cessation trials. The
clear effect of smoking cessation on MS progression suggests the need to consider
adjusting for smoking cessation when assessing for treatment effects in clinical
trials of treatments for MS. Smoking cessation should be an early intervention in
people with MS.
PMID- 28402455
TI - Stage I non-small-cell lung cancer: long-term results of lobectomy versus
sublobar resection from the Polish National Lung Cancer Registry.
AB - OBJECTIVES: Anatomical lobar resection and mediastinal lymphadenectomy remain the
standard for the treatment of early stage non-small-cell lung cancer (NSCLC) and
are preferred over procedures such as segmentectomy or wedge resection. However,
there is an ongoing debate concerning the influence of the extent of the
resection on overall survival. The aim of this article was to assess the overall
survival for different types of resection for Stage I NSCLC. METHODS: We
performed a retrospective analysis of the results of the surgical treatment of
Stage I NSCLC. Between 1 January 2007 and 31 December 2013, the data from 6905
patients who underwent Stage I NSCLC operations were collected in the Polish
National Lung Cancer Registry (PNLCR) and overall survival was assessed. A
propensity score-matched analysis was used to compare 3 groups of patients, each
consisting of 231 patients who underwent lobectomy, segmentectomy, or wedge
resection. RESULTS: In the unmatched and matched patient groups, lobectomy and
segmentectomy were associated with a significant benefit compared to wedge
resection regarding overall survival (log-rank P < 0.001 and P = 0.001). The
Cox proportional hazard ratio comparing segmentectomy and lobectomy to wedge
resection was 0.54 [95% confidence interval (CI): 0.37-0.77) and 0.44 (95% CI:
0.38-0.50), respectively, indicating a significant improvement in survival. There
was no difference in the 5-year survival of patients after lobectomy (79.1%; 95%
CI: 77.7-80.4%) or segmentectomy (78.3%; 95% CI: 70.6-86.0%). The 30-day
mortality rate was 1.6, 2.6 and 1.4% for lobectomy, segmentectomy and wedge
resection, respectively. Wedge resection was associated with a significantly
lower 5-year survival rate (58.1%; 95% CI: 53.6-62.5%) compared to segmentectomy
(78.3%; 95% CI: 70.6-86.0%) and lobectomy (79.1%; 95% CI: 77.7-80.5%). The
propensity score matched analysis confirmed most of the results of the
comparisons of unmatched study groups. CONCLUSIONS: Wedge resection was
associated with significantly lower 3-year and 5-year survival rates compared to
the other methods of resection. There was no significant difference in 3-year or
5-year survival rates between lobectomy and segmentectomy. Segmentectomy, but not
wedge resection, could be considered an alternative to lobectomy in the treatment
of patients with Stage I NSCLC.
PMID- 28402457
TI - Analysis of Cost Variation in Craniotomy for Tumor Using 2 National Databases.
AB - BACKGROUND: There is a significant increase and large variation in craniotomy
costs. However, the causes of cost differences in craniotomies remain poorly
understood. OBJECTIVE: To examine the patient and hospital factors that underlie
the cost variation in tumor craniotomies using 2 national databases: the National
Inpatient Sample (NIS) and Vizient, Inc. (Irving, Texas). METHODS: For 41 483
patients who underwent primary surgery for supratentorial brain tumors from 2001
to 2013 in the NIS, we created univariate and multivariate models to evaluate the
effect of several patient factors and hospital factors on total hospital cost.
Similarly, we performed multivariate analysis with 15 087 cases in the Vizient
2012 to 2015 database. RESULTS: In the NIS, the mean inflation-adjusted cost per
tumor craniotomy increased 30%, from $23 021 in 2001 to $29 971 in 2013. In 2001,
the highest cost region was the Northeast ($24 486 +/- $1184), and by 2013 the
western United States was the highest cost region ($36 058 +/- $1684).
Multivariate analyses with NIS data showed that male gender, white race, private
insurance, higher mortality risk, higher severity of illness, longer length of
stay, elective admissions, higher wage index, urban teaching hospitals, and
hospitals in the western United States were associated with higher tumor
craniotomy costs (all P < .05). Multivariate analyses with Vizient data confirmed
that longer length of stay and the western United States were significantly
associated with higher costs (P < .001). CONCLUSION: After controlling for
patient/clinical factors, hospital type, bed size, and wage index, hospitals in
the western United States had higher costs than those in other parts of the
country, based on analyses from 2 separate national databases.
PMID- 28402458
TI - The Influence of Pelvic Incidence and Lumbar Lordosis Mismatch on Development of
Symptomatic Adjacent Level Disease Following Single-Level Transforaminal Lumbar
Interbody Fusion.
AB - BACKGROUND: Annual incidence of symptomatic adjacent level disease (ALD)
following lumbar fusion surgery ranges from 0.6% to 3.9% per year. Sagittal
malalignment may contribute to the development of ALD. OBJECTIVE: To describe the
relationship between pelvic incidence-lumbar lordosis (PI-LL) mismatch and the
development of symptomatic ALD requiring revision surgery following single-level
transforaminal lumbar interbody fusion for degenerative lumbar spondylosis and/or
low-grade spondylolisthesis. METHODS: All patients who underwent a single-level
transforaminal lumbar interbody fusion at either L4/5 or L5/S1 between July 2006
and December 2012 were analyzed for pre- and postoperative spinopelvic
parameters. Using univariate and logistic regression analysis, we compared the
spinopelvic parameters of those patients who required revision surgery against
those patients who did not develop symptomatic ALD. We calculated the predictive
value of PI-LL mismatch. RESULTS: One hundred fifty-nine patients met the
inclusion criteria. The results noted that, for a 1 degrees increase in PI-LL
mismatch (preop and postop), the odds of developing ALD requiring surgery
increased by 1.3 and 1.4 fold, respectively, which were statistically significant
increases. Based on our analysis, a PI-LL mismatch of >11 degrees had a positive
predictive value of 75% for the development of symptomatic ALD requiring revision
surgery. CONCLUSIONS: A high PI-LL mismatch is strongly associated with the
development of symptomatic ALD requiring revision lumbar spine surgery. The
development of ALD may represent a global disease process as opposed to a focal
condition. Spine surgeons may wish to consider assessment of spinopelvic
parameters in the evaluation of degenerative lumbar spine pathology.
PMID- 28402459
TI - Spine Topographical Distribution of Skin alpha-Synuclein Deposits in Idiopathic
Parkinson Disease.
AB - Phosphorylated alpha-synuclein (p-syn) in skin nerves mainly in the proximal
sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease
(IPD). However, the p-syn spine distribution particularly in patients with
unilateral motor dysfunctions remains undefined. This study aimed to investigate
in IPD p-syn differences between left and right cervical spine sites in patients
with prevalent unilateral motor symptoms, and cervical and thoracic spine sites
in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling
clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and
cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by
DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients
underwent skin biopsy searching for intraneural p-syn deposits: skin samples were
taken from C7 paravertebral left and right sites in unilateral patients and from
cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral
patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the
affected motor site, 60% in both sites and 20% only in the non-affected site. P
syn was found in all patients in C7 but in only 62% of patients in Th12. Our data
showed that cervical p-syn deposits displayed a uniform distribution between both
sides not following the motor dysfunction in unilateral patients, and skin nerve
p-syn deposits demonstrated a spine gradient with the cervical site expressing
the highest positivity.
PMID- 28402460
TI - Letter: Carotid Artery Angioplasty and Stenting Without Distal Embolic Protection
Devices.
PMID- 28402461
TI - Left atrial appendage empirical electrical isolation for persistent atrial
fibrillation: time for a change in practice.
PMID- 28402462
TI - Omicseq: a web-based search engine for exploring omics datasets.
AB - The development and application of high-throughput genomics technologies has
resulted in massive quantities of diverse omics data that continue to accumulate
rapidly. These rich datasets offer unprecedented and exciting opportunities to
address long standing questions in biomedical research. However, our ability to
explore and query the content of diverse omics data is very limited. Existing
dataset search tools rely almost exclusively on the metadata. A text-based query
for gene name(s) does not work well on datasets wherein the vast majority of
their content is numeric. To overcome this barrier, we have developed Omicseq, a
novel web-based platform that facilitates the easy interrogation of omics
datasets holistically to improve 'findability' of relevant data. The core
component of Omicseq is trackRank, a novel algorithm for ranking omics datasets
that fully uses the numerical content of the dataset to determine relevance to
the query entity. The Omicseq system is supported by a scalable and elastic,
NoSQL database that hosts a large collection of processed omics datasets. In the
front end, a simple, web-based interface allows users to enter queries and
instantly receive search results as a list of ranked datasets deemed to be the
most relevant. Omicseq is freely available at http://www.omicseq.org.
PMID- 28402463
TI - Dynamics of insertion sequence element IS629 inactivation of verotoxin 2 genes in
Escherichia coli O157:H7.
AB - There are several anecdotal reports of insertion sequence (IS) element
inactivation of verotoxin genes among enterohaemorrhagic Escherichia coli of the
serotype O157:H7, a pathogen causing severe gastrointestinal disease in infected
humans. These insertions can be expected to drastically reduce the virulence of
the bacteria. IS element inactivation has been shown to be reversible in model
systems, suggesting the possibility of spontaneous restoration of virulence. In
this study, traditional and high-throughput sequencing was used to characterise
three patterns of IS629 inactivation of verotoxin 2 genes in EHEC O157:H7, caused
by insertion or insertion followed by partial deletion. At least one of the
patterns of inactivation appears to have persisted several years among cattle
O157:H7, indicating it has no major effect on fitness in the animal reservoir.
Digital PCR was used to directly quantify the reversal rates of the insertional
inactivation of a selected isolate under laboratory conditions. Inserts were
found to be absent from in the order of 1/105 of individual genomes, with
significantly higher loss frequencies observed in cultures under nutrient-poor
conditions. We conclude that strains with this type of inactivation found in food
or animal samples should be considered a threat to human health, and may pose a
challenge for PCR-based detection methods.
PMID- 28402465
TI - Hospital Length of Stay and Readmission Rate for Neurosurgical Patients.
AB - BACKGROUND: Hospital readmission rate has become a major indicator of quality of
care, with penalties given to hospitals with high rates of readmission. At the
same time, insurers are increasing pressure for greater efficiency and reduced
costs, including decreasing hospital lengths of stay (LOS). OBJECTIVE: To analyze
the authors' service to determine if there is a relationship between LOS and
readmission rates. METHODS: Records of patients admitted to the authors'
institution from October 2007 through June 2014 were analyzed for several data
points, including initial LOS, readmission occurrence, admitting and secondary
diagnoses, and discharge disposition. RESULTS: Out of 9409 patient encounters,
there were 925 readmissions. Average LOS was 6 d. Univariate analysis indicated a
higher readmission rate with more diagnoses upon admission (P < .001) and an
association between insurance type and readmission (P < .001), as well as
decreasing average yearly LOS (P = .0045). Multivariate analysis indicated
statistically significant associations between longer LOS (P = .03) and
government insurance (P < .01). CONCLUSION: A decreasing LOS over time has been
associated with an increasing readmission rate at the population level. However,
at the individual level, a prolonged LOS was associated with a higher risk of
readmission. This was attributed to patient comorbidities. However, this
increasing readmission rate may represent many factors including patients'
overall health status. Thus, the rate of readmission may represent a burden of
illness rather than a valid metric for quality of care.
PMID- 28402464
TI - Economic Downturns, Retirement and Long-Term Cognitive Function Among Older
Americans.
AB - Objective: Workers approaching retirement may be particularly vulnerable to
economic downturns. This study assesses whether exposure to economic downturns
around retirement age leads to poorer cognitive function in later life. Method:
Longitudinal data for 13,577 individuals in the Health and Retirement Study were
linked to unemployment rates in state of residence. Random- and fixed-effect
models were used to examine whether downturns at 55-64 years of age were
associated with cognitive functioning levels and decline at >=65 years, measured
by the Wechsler Adult Intelligence Scale-Revised. Results: Longer exposure to
downturns at 55-64 years of age was associated with lower levels of cognitive
function at >=65 years. Compared to individuals experiencing only up to 1 year in
a downturn at 55-64 years of age, individuals experiencing two downturns at these
ages had 0.09 point (95% Confidence Interval [CI, -0.17, -0.02]) lower cognitive
functioning scores at >=65 years (3 years: b = -0.17, 95%CI [-0.29, -0.06]; 4
years: b = -0.14, 95%CI [-0.25, -0.02]; >=5 years: b = -0.22, 95%CI [-0.38,
0.06]). Downturns at 55-64 years of age were not associated with rates of
cognitive decline. Discussion: Exposure to downturns around retirement is
associated with a long-lasting decline in cognitive function in later life.
Policies mitigating the impact of downturns on older workers may help to maintain
cognitive function in later life.
PMID- 28402466
TI - Efficacy of Nootka Oil as a Biopesticide for Management of Imported Fire Ants
(Hymenoptera: Formicidae).
AB - Recent concerns regarding the impact of traditional synthetic pesticides on
nontarget organisms have generated demand for alternative products with lower
environmental impact. This demand has led to increasing focus on plant essential
oils as sources of new biopesticides. In this study, we demonstrate that the
essential oil of the Alaskan yellow cedar, Cupressus nootkatensis (D. Don) Spach,
has activity against hybrid imported fire ant workers, Solenopsis invicta Buren *
Solenopsis richteri Forel. In digging assays, ants were repelled by nootka oil
and digging continued to be suppressed by nearly 50% in nootka oil-treated sand
aged 6 mo in the laboratory. Higher worker mortality was also observed in contact
and fumigation assays compared to control checks. In a field drench test,
mortality of mounds treated with nootka oil lagged behind mounds treated with
bifenthrin treatment for 7 wk, but both nootka oil and bifenthrin had higher
mortality than the untreated check at the end of the 12-wk evaluation period. In
a band application evaluation, nootka oil plots maintained a 90-95% reduction in
fire ant mounds from the 2nd to 17th wk, when new mounds began to intrude on the
field plots. The quarantine-approved bifenthrin band treatment maintained 100%
control from the 2nd to 24th wk. Although the formulation tested here did not
perform to Federal Imported Fire Ant Quarantine standards, other formulations may
enable this product to reach 100% control. In addition, nootka oil could be
beneficial in situations where ant suppression rather than complete quarantine
elimination is the management goal.
PMID- 28402467
TI - Natural History and Risk Factor of Recurrent Hemorrhage in Hemorrhagic Adult
Moyamoya Disease.
AB - BACKGROUND: Recurrent hemorrhage is a serious neurosurgical problem in adult
moyamoya disease (MMD) patients. OBJECTIVE: To find the natural history and risk
factors of recurrent hemorrhage in cases of adult hemorrhagic MMD. METHODS: One
hundred seventy-six adult MMD patients presenting with hemorrhage were enrolled.
Patients' medical records and radiological images were retrospectively reviewed.
Clinical and radiological features of recurrent hemorrhage, and related risk
factors were analyzed. Poor neurological outcome was defined as a score on the
modified Rankin Scale of 4 to 6. The hemisphere in which the initial hemorrhage
occurred was considered as the affected one. The mean follow-up duration was 83
months. RESULTS: The overall estimated rate of recurrent hemorrhage was
16.9%/person (95% confidence interval, 11.3%-24.8%) at 5 years and 26.3%/person
(95% confidence interval, 18.5%-36.4%) at 10 years after the initial episode of
hemorrhage. The affected hemisphere showed a higher recurrent hemorrhagic rate
(11.7% vs 8.3%/hemisphere at 5 years, P = .09) after conservative treatment. As a
result of recurrent hemorrhages, the number of patients with poor neurological
outcome increased (first episode: 13.8%, second: 37.5%, third: 40.0%, fourth:
100%). The presence of intraventricular hemorrhage ( P = .05, hazard ratio =
3.32) and bilateral MMD ( P = .05, hazard ratio = 4.15) had a marginal
significance for recurrent hemorrhage. Eight ischemic strokes (4.5%) including 4
postoperative infarctions were identified, and all ischemic strokes were minor
stroke. CONCLUSION: During the follow-up period, recurrent hemorrhagic events
continued to increase and deteriorated the patients' neurological conditions. The
presence of intraventricular hemorrhage was a significant risk factor of
recurrent hemorrhage.
PMID- 28402468
TI - Xylem adjustment of sessile oak at its southern distribution limits.
AB - Drought is a key limiting factor for tree growth in the Mediterranean Basin.
However, the variability in acclimation via xylem traits is largely unknown. We
studied tree growth and vessel features of Quercus petraea (Matt.) Lieb. in five
marginal stands across southern Europe. Tree-ring width (TRW), mean earlywood
vessel area (MVA) and number of earlywood vessels (NV) as well as theoretical
hydraulic conductivity (Kh) chronologies were developed for the period 1963-2012.
Summer drought signals were consistent among TRW chronologies; however, climatic
responses of vessel features differed considerably among sites. At the three
xeric sites, previous year's summer drought had a negative effect on MVA and a
positive effect on NV. In contrast, at the two mesic sites, current year's spring
drought negatively affected NV, while exerting a positive influence on MVA. In
both cases, Kh was not altered by this xylem adjustment. All variables revealed
identical east-west geographical patterns in growth and anatomical features.
Sessile oak copes with drought in different ways: at xeric sites and after
unfavourable previous summer conditions more but smaller vessels are built,
lowering vulnerability to cavitation, whereas at mesic sites, dry springs partly
lead to tree-rings with wider but fewer vessels. The variability of vessel
related features displays a similar geographical dipole in the Mediterranean
Basin previously described for tree growth by other studies.
PMID- 28402469
TI - Health system functionality in a low-income country in the midst of conflict: the
case of Yemen.
AB - Background: Although the literature on effects of armed conflict on population
health is extensive, detailed assessments of effects on public health 'systems'
are few. This article aims to help address this deficit through the medium of a
case study on Yemen, describing health system and health outcome performance
prior to the internationalisation of the conflict there in March 2015, before
assessing the impact of war on health system functionality since that time.
Method : Review of peer- and non-peer reviewed literature from 2005 to 2016 from
academic sources, multilateral organizations, donors and governmental and non
governmental organizations, augmented by secondary data analysis. Results :
Despite significant health system weaknesses and structural vulnerabilities pre
conflict, there were important improvements in selected health outcome measures
in Yemen up to early 2015 (life expectancy, and infant and maternal mortality,
e.g.), partly driven by a fragile health sector that was heavily reliant on out
of-pocket expenditure, and hampered by weak service penetration especially in
rural areas. High intensity conflict has resulted in rising mortality and injury
rates since March 2015, the first decline in life expectancy and increase in
child and maternal mortality in Yemen for some years, and worsening levels of
malnutrition. Service delivery has become increasingly challenging in the context
of a funding crisis, destruction of health facilities, widespread shortages of
essential medicines and equipment across the country, and governance
fragmentation. Conclusion : Conflict in Yemen has resulted in humanitarian
disaster on a wide scale in a short period of time, and crippled an already weak
health system. Important areas of uncertainty remain, however, including the
scale of health worker flight, and the extent to which alternative providers have
stepped in to fill widening service gaps as the conflict has unfolded. Planning
for longer-term health system reconstruction should begin as soon as possible.
PMID- 28402470
TI - Proper authentication of ancient DNA is essential, yes; but so are undogmatic
approaches.
PMID- 28402471
TI - Non-specific effects of BCG vaccination on morbidity among children in Greenland
an answer to a relevant question.
PMID- 28402472
TI - Direct sternal administration of Vancomycin and Gentamicin during closure
prevents wound infection.
AB - OBJECTIVES: Deep sternal wound infection is still a major complication in
patients undergoing cardiac surgery. We previously identified mammary artery
harvesting as a risk factor for decreased antibiotic tissue penetration. In
addition, other risk factors including diabetes may inhibit sufficient tissue
penetration of perioperative antibiotic prophylaxis. A novel closure protocol
applying 2 topical antibiotics and further recommendations for sternal wiring was
introduced at our department to decrease the incidence of sternal wound
infections. METHODS: A 12-month period prior to (March 2013-February 2014) and
after (July 2014-June 2015) the introduction of a novel sternal closure protocol
was studied. All sternal wound infections resulting from an operation during this
period were analysed. The closure protocol consisted of the intra-sternal
application of vancomycin and the subcutaneous application of gentamicin.
Furthermore, we increased the number of sternal wires for more uniform
distribution of lateral forces. RESULTS: Patients in both groups were comparable
regarding demographic data and risk factors. Fifty-three out of 919 patients
operated prior to the protocol change developed an infection (5.8%). The
introduction of the novel sternal closure protocol reduced this number to 19 out
of 932 patients (2.0%; P < 0.001). A binary regression including common risk
factors revealed a strong independent risk reduction by the novel protocol (OR
0.322, P < 0.001). The number of sternal wires was not significant in this
analysis. CONCLUSIONS: The topical application of 2 antibiotic agents
significantly reduced sternal wound infection. However, the results of this trial
should be confirmed in a randomized trial.
PMID- 28402473
TI - Cavernous Malformation Associated With Arterialized Developmental Venous Anomaly:
A Case Report.
AB - BACKGROUND AND IMPORTANCE: Formation of cavernous malformations (CMs) has been
recognized to be associated with developmental venous anomaly (DVA) by many
authors. Hemodynamic stress due to venous outflow restriction could be
hypothesized as a cause. On the other hand, a rare subgroup of DVA with an
arterial component has been reported as likely to hemorrhage or be symptomatic.
Cases of arterialized DVAs reported previously have not been associated with the
presence of CM. CLINICAL PRESENTATION: We present herein a case report of
arterialized DVA in the brainstem with repeated cerebellar hemorrhage. The 49
year-old patient was treated with surgical evacuation of hematoma. A surgical
specimen from the hematoma cavity demonstrated CMs on histological examination.
CONCLUSION: To the best of our knowledge, this represents the first report of CM
associated with an arterialized DVA. In addition to venous congestion due to
outflow obstruction, bleeding from the arterial component of the DVA might be
considered as a cause of CM formation.
PMID- 28402474
TI - The Nursing Home Physical Performance Test: A Secondary Data Analysis of Women in
Long-Term Care Using Item Response Theory.
AB - Background and Objectives: The Nursing Home Physical Performance Test (NHPPT) was
developed to measure function among nursing home residents using sit-to-stand,
scooping applesauce, face washing, dialing phone, putting on sweater, and
ambulating tasks. Using item response theory, we explore its measurement
characteristics at item level and opportunities for improvements. Research Design
and Methods: We used data from long-term care women. We fitted a graded response
model, estimated parameters, and constructed probability and information curves.
We identified items to be targeted toward lower and higher functioning persons to
increase the range of abilities to which the instrument is applicable. We revised
the scoring by making sit-to-stand and sweater items harder and dialing phone
easier. We examined changes to concurrent validity with activities of daily
living (ADL), frailty, and cognitive function. Results: Participants were 86
years old, had more than three comorbidities, and a NHPPT of 19.4. All items had
high discrimination and were targeted toward the lower middle range of
performance continuum. After revision, sit-to-stand and sweater items
demonstrated greater discrimination among the higher functioning and/or greater
spread of thresholds for response categories. The overall test showed
discrimination over a wider range of individuals. Concurrent validity correlation
improved from 0.60 to 0.68 for instrumental ADL and explained variability (R2)
from 22% to 36% for frailty. Discussion and Implications: NHPPT has good
measurement characteristics at the item level. NHPPT can be improved, implemented
in computerized adaptive testing, and combined with self-report for greater
utility, but a definitive study is needed.
PMID- 28402475
TI - ReFOLD: a server for the refinement of 3D protein models guided by accurate
quality estimates.
AB - ReFOLD is a novel hybrid refinement server with integrated high performance
global and local Accuracy Self Estimates (ASEs). The server attempts to identify
and to fix likely errors in user supplied 3D models of proteins via successive
rounds of refinement. The server is unique in providing output for multiple
alternative refined models in a way that allows users to quickly visualize the
key residue locations, which are likely to have been improved. This is important,
as global refinement of a full chain model may not always be possible, whereas
local regions, or individual domains, can often be much improved. Thus, users may
easily compare the specific regions of the alternative refined models in which
they are most interested e.g. key interaction sites or domains. ReFOLD was used
to generate hundreds of alternative refined models for the CASP12 experiment,
boosting our group's performance in the main tertiary structure prediction
category. Our successful refinement of initial server models combined with our
built-in ASEs were instrumental to our second place ranking on Template Based
Modeling (TBM) and Free Modeling (FM)/TBM targets. The ReFOLD server is freely
available at: http://www.reading.ac.uk/bioinf/ReFOLD/.
PMID- 28402476
TI - Silent atrial fibrillation in pacemaker early post-implantation period: an
unintentionally provoked situation?
AB - Aims: Atrial high-rate episodes (AHREs) compatible with silent AF detected in
pacemakers (PM) are related to an increased risk of stroke and silent ischaemic
brain lesions (IBL) on CT scan. AHREs soon after PM implantation could be related
with the procedure itself and the prognosis might be different. Methods and
results: We analysed the incidence of AHREs >5 min and the presence of silent IBL
in 110 patients (56% men, aged 75 +/- 9 year-old) with PM and no history of AF,
in relation to time from implantation (<=3 months vs. >3 months) and the atrial
lead fixation (LF) (active vs. passive). Mean CHADS2 and CHA2DS2VASc scores were
1.9 +/- 1.2 and 3.5 +/- 1.5, respectively. Time from implantation was <=3 months
in 88 patients (80%). Active LF was used in 55 patients (50%). After 24 +/- 9
months, AHREs were present in 40 patients (36.4%). CT-scan showed silent IBL in
26 patients (23.6%). The presence of AHREs at 3 months was more frequent in the
patients with recent PM implantation (17% vs. 4.5%, P = 0.09) and significantly
related to active LF (OR 5.36, 1.43-20.07; P < 0.05). The presence of silent IBL
was related to the detection of AHREs during follow up (OR 3.12, 1.29-7.97; P <
0.05) but not with AHREs at first 3 months (OR 1.58, 0.49-5.05; P = 0.44).
Conclusions: AHREs occur frequently during the first 3 months after PM
implantation and could be related with procedure itself and the use of active LF.
AHREs in this period might not be related to worse outcomes and should be
interpreted cautiously.
PMID- 28402477
TI - Coercive and legitimate authority impact tax honesty: evidence from behavioral
and ERP experiments.
AB - Cooperation in social systems such as tax honesty is of central importance in our
modern societies. However, we know little about cognitive and neural processes
driving decisions to evade or pay taxes. This study focuses on the impact of
perceived tax authority and examines the mental chronometry mirrored in ERP data
allowing a deeper understanding about why humans cooperate in tax systems. We
experimentally manipulated coercive and legitimate authority and studied its
impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal
(experiment 2) processes. Experiment 1 showed that in a condition of coercive
authority, tax payments are lower, decisions are faster and participants report
more rational reasoning and enforced compliance, however, less voluntary
cooperation than in a condition of legitimate authority. Experiment 2 confirmed
most results, but did not find a difference in payments or self-reported rational
reasoning. Moreover, legitimate authority led to heightened cognitive control
(expressed by increased MFN amplitudes) and disrupted attention processing
(expressed by decreased P300 amplitudes) compared to coercive authority. To
conclude, the neuronal data surprisingly revealed that legitimate authority may
led to higher decision conflict and thus to higher cognitive demands in tax
decisions than coercive authority.
PMID- 28402478
TI - The neural basis of emotions varies over time: different regions go with onset-
and offset-bound processes underlying emotion intensity.
AB - According to theories of emotion dynamics, emotions unfold across two phases in
which different types of processes come to the fore: emotion onset and emotion
offset. Differences in onset-bound processes are reflected by the degree of
explosiveness or steepness of the response at onset, and differences in offset
bound processes by the degree of accumulation or intensification of the
subsequent response. Whether onset- and offset-bound processes have distinctive
neural correlates and, hence, whether the neural basis of emotions varies over
time, still remains unknown. In the present fMRI study, we address this question
using a recently developed paradigm that allows to disentangle explosiveness and
accumulation. Thirty-one participants were exposed to neutral and negative social
feedback, and asked to reflect on its contents. Emotional intensity while reading
and thinking about the feedback was measured with an intensity profile tracking
approach. Using non-negative matrix factorization, the resulting profile data
were decomposed in explosiveness and accumulation components, which were
subsequently entered as continuous regressors of the BOLD response. It was found
that the neural basis of emotion intensity shifts as emotions unfold over time
with emotion explosiveness and accumulation having distinctive neural correlates.
PMID- 28402479
TI - Perception of social synchrony induces mother-child gamma coupling in the social
brain.
AB - The recent call to move from focus on one brain's functioning to two-brain
communication initiated a search for mechanisms that enable two humans to
coordinate brain response during social interactions. Here, we utilized the
mother-child context as a developmentally salient setting to study two-brain
coupling. Mothers and their 9-year-old children were videotaped at home in
positive and conflictual interactions. Positive interactions were microcoded for
social synchrony and conflicts for overall dialogical style. Following, mother
and child underwent magnetoencephalography while observing the positive
vignettes. Episodes of behavioral synchrony, compared to non-synchrony, increased
gamma-band power in the superior temporal sulcus (STS), hub of social cognition,
mirroring and mentalizing. This neural pattern was coupled between mother and
child. Brain-to-brain coordination was anchored in behavioral synchrony; only
during episodes of behavioral synchrony, but not during non-synchronous moments,
mother's and child's STS gamma power was coupled. Importantly, neural synchrony
was not found during observation of unfamiliar mother-child interaction Maternal
empathic/dialogical conflict style predicted mothers' STS activations whereas
child withdrawal predicted attenuated STS response in both partners. Results
define a novel neural marker for brain-to-brain synchrony, highlight the role of
rapid bottom-up oscillatory mechanisms for neural coupling and indicate that
behavior-based processes may drive synchrony between two brains during social
interactions.
PMID- 28402480
TI - Cognitive benefit and cost of acute stress is differentially modulated by
individual brain state.
AB - Acute stress is associated with beneficial as well as detrimental effects on
cognition in different individuals. However, it is not yet known how stress can
have such opposing effects. Stroop-like tasks typically show this dissociation:
stress diminishes speed, but improves accuracy. We investigated accuracy and
speed during a stroop-like task of 120 healthy male subjects after an
experimental stress induction or control condition in a randomized, counter
balanced cross-over design; we assessed brain-behavior associations and
determined the influence of individual brain connectivity patterns on these
associations, which may moderate the effect and help identify stress resilience
factors. In the mean, stress was associated to increase in accuracy, but decrease
in speed. Accuracy was associated to brain activation in a distributed set of
brain regions overlapping with the executive control network (ECN) and speed to
temporo-parietal activation. In line with a stress-related large-scale network
reconfiguration, individuals showing an upregulation of the salience and down
regulation of the executive-control network under stress displayed increased
speed, but decreased performance. In contrast, individuals who upregulate their
ECN under stress show improved performance. Our results indicate that the
individual large-scale brain network balance under acute stress moderates
cognitive consequences of threat.
PMID- 28402481
TI - Identification and functional analyses of novel antioxidant peptides and
antimicrobial peptides from skin secretions of four East Asian frog species.
AB - In the present study, we identified 50 peptides that are classified into 21
peptide families with antioxidant and/or antimicrobial activity from Amolops
daiyunensis, Pelophylax hubeiensis, Hylarana maosuoensis and Nanorana pleskei,
which belong to four different genera in the Ranidae and Dicroglossidae families.
These four frog species were found for the first time to express antioxidant
peptides (AOPs) and antimicrobial peptides (AMPs). These peptides include seven
newly discovered families daiyunin-1, daiyunin-2, daiyunin-3, maosonensis-1MS1,
pleskein-1, pleskein-2, and pleskein-3. Antioxidant and antimicrobial activity
assays showed that some of these peptides have good biological activities. For
example, at a concentration of 50 MUM, nigroain-B-MS1, and nigroain-C-MS1 both
exhibited relatively strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'
azinobis-(3-ethylbenzothiazoline-6-sulfonicacid) (ABTS) free radical scavenging
ability, with eradication rates of 99.7% and 68.3% (nigroain-B-MS1), and 99.8%
and 58.3% (nigroain-C-MS1), respectively. These peptides are potential candidates
for the development of novel antioxidant or AMP preparations.
PMID- 28402483
TI - Variable selection should be blinded to the outcome.
PMID- 28402482
TI - Are Prescription Opioids Driving the Opioid Crisis? Assumptions vs Facts.
AB - Objective: Sharp increases in opioid prescriptions, and associated increases in
overdose deaths in the 2000s, evoked widespread calls to change perceptions of
opioid analgesics. Medical literature discussions of opioid analgesics began
emphasizing patient and public health hazards. Repetitive exposure to this
information may influence physician assumptions. While highly consequential to
patients with pain whose function and quality of life may benefit from opioid
analgesics, current assumptions about prescription opioid analgesics, including
their role in the ongoing opioid overdose epidemic, have not been scrutinized.
Methods: Information was obtained by searching PubMed, governmental agency
websites, and conference proceedings. Results: Opioid analgesic prescribing and
associated overdose deaths both peaked around 2011 and are in long-term decline;
the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and
heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co
ingested benzodiazepines, alcohol, or other central nervous system/respiratory
depressants, are infrequent. Within five years of initial prescription opioid
misuse, 3.6% initiate heroin use. The United States consumes 80% of the world
opioid supply, but opioid access is nonexistent for 80% and severely restricted
for 4.1% of the global population. Conclusions: Many current assumptions about
opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid
prescribing, now fuel the current opioid overdose epidemic. National discussion
has often neglected the potentially devastating effects of uncontrolled chronic
pain. Opioid analgesic prescribing and related overdoses are in decline, at great
cost to patients with pain who have benefited or may benefit from, but cannot
access, opioid analgesic therapy.
PMID- 28402484
TI - Location of Disease on Imaging may Predict Radiation Exposure During Endoscopic
Retrograde Cholangiopancreatography.
AB - Endoscopic retrograde cholangiopancreatography (ERCP) is performed for various
diseases. The aim of this study is to evaluate the difference of dose-area
product (DAP) during the ERCP procedures according to location of the lesion. We
performed a retrospective study of consecutive 217 therapeutic ERCP examinations
performed between November 2014 and April 2015 at a tertiary care center. ERCP
procedures divided into two groups according to location of the lesion identified
on imaging: lesions in the common hepatic duct (CHD) or the common bile duct
(CBD) and lesions in the hepatic hilum or the intrahepatic duct (IHD). The mean
DAP of the hilum-IHD group (48.7 Gy cm2) was significantly higher than that of
the CBD-CHD group (34.9 Gy cm2) (P = 0.003). Radiation exposure during ERCP was
significantly different according to location of bile duct lesion.
PMID- 28402485
TI - Evolution of Sagittal Imbalance Following Corrective Surgery for Sagittal Plane
Deformity.
AB - BACKGROUND: Sagittal balance in adult spinal deformity is a major predictor of
quality of life. A temporary loss of paraspinal muscle force and somatic pain
following spine surgery may limit a patient's ability to maintain posture.
OBJECTIVE: To assess the evolution of sagittal balance and clinical outcomes
during recovery from adult spinal deformity surgery. METHODS: Retrospective
review of a prospective observational database identified a consecutive series of
patients with sagittal vertical axis (SVA) > 40 mm undergoing adult deformity
surgery. Radiographic parameters and clinical outcomes were measured out to 2 yr
after surgery. RESULTS: A total of 113 consecutive patients met inclusion
criteria. Mean preoperative SVA was 90.3 mm, increased to 104.6 mm in the first
week, then gradually reduced at each follow-up interval to 59.2 mm at 6 wk, 45.0
mm at 3 mo, 38.6 mm at 6 mo, and 34.1 mm at 1 yr (all P < .05). SVA did not
change between 1 and 2 yr. Pelvic incidence-lumbar lordosis (PI-LL) corrected
immediately from 25.3 degrees to 8.5 degrees (16.8 degrees change; P < .01)
and a decreased pelvic tilt from 27.6 degrees to 17.6 degrees (10 degrees
change; P < .01). No further change was noted in PI-LL. Pelvic tilt increased to
20.2 degrees ( P = .01) at 6 wk and held steady through 2 yr. Mean Visual Analog
Scale, Oswestry Disability Index, and Short Form-36 scores all improved; pain
rapidly improved, whereas disability measures improved as SVA improved.
CONCLUSION: Radiographic assessment of global sagittal alignment did not fully
reflect surgical correction of sagittal balance until 6 mo after adult deformity
surgery. Sagittal balance initially worsened then steadily improved at each
interval over the first year postoperatively. At 1 yr, all clinical and
radiographic measures outcomes were significantly improved.
PMID- 28402486
TI - The iterative nature of person construal: Evidence from event-related potentials.
AB - Recently, a dynamic-interactive model of person construal (DI model) has been
proposed, whereby the social categories a person represents are determined on the
basis of an iterative integration of bottom-up and top-down influences. The
current study sought to test this model by leveraging the high temporal
resolution of event-related brain potentials (ERPs) as 65 participants viewed
male faces that varied by race (White vs Black), fixating either between the eyes
or on the forehead. Within face presentations, the effect of fixation, meant to
vary bottom-up visual input, initially was large but decreased across early
latency neural responses identified by a principal components analysis (PCA). In
contrast, the effect of race, reflecting a combination of top-down and bottom-up
factors, initially was small but increased across early latency principal
components. These patterns support the DI model prediction that bottom-up and top
down processes are iteratively integrated to arrive at a stable construal within
230 ms. Additionally, exploratory multilevel modeling of single trial ERP
responses representing a component linked to outgroup categorization (the P2)
suggests change in effects of the manipulations over the course of the
experiment. Implications of the findings for the DI model are considered.
PMID- 28402487
TI - Circulating Klotho Associates With Cardiovascular Morbidity and Mortality During
Hemodialysis.
AB - Background: Klotho gene was identified as an aging suppressor. In animals, klotho
overexpression extends life span, and defective klotho results in rapid aging and
early death. The kidney is the main contributor to circulating klotho levels,
and, during chronic kidney disease, renal klotho gene expression is drastically
reduced in animals and humans as well. Objective: We aimed to determine the
consequences of a serum klotho (seKL) defect on cardiovascular morbidity and
mortality during chronic dialysis. Design: The ARNOGENE study was designed to
prospectively follow a cohort of hemodialysis patients for 2 years without
specific intervention. A total of 769 patients was recruited and followed from
the end of 2008 until January 2011. A total of 238 patients was analyzed due to a
technical sample conservation issue with other samples. Results: The median seKL
was markedly reduced, 360.4 ng/L (interquartile range 176.5) as compared with
nondialysis chronic kidney disease patients or healthy volunteers. Patients with
a seKL above the first quartile (>=280 ng/L) had a significantly reduced
occurrence of outcome combining cardiovascular events and cardiovascular death
[odds ratio (OR) = 0.39; 0.19 to 0.78, P = 0.008] compared with patient with
klotho <280 ng/L. This effect persisted (OR = 0.86; 0.76 to 0.99, P = 0.03) after
adjustment on age, sex, diabetes, cardiac insufficiency, dialysis vintage, and
serum hemoglobin, albumin, fibroblast growth factor-23, phosphate, and calcium.
Conclusions: These results suggest that, during chronic hemodialysis,
conservation of seKL >280 ng/L is associated with a better 2-year cardiovascular
protection. Thus, a preserved klotho function supports cardiovascular protection
and may represent a prognostic tool and therapeutic target for cardiovascular
disease.
PMID- 28402488
TI - Evaluation of the 24-Hour Recall as a Reference Instrument for Calibrating Other
Self-Report Instruments in Nutritional Cohort Studies: Evidence From the
Validation Studies Pooling Project.
AB - Calibrating dietary self-report instruments is recommended as a way to adjust for
measurement error when estimating diet-disease associations. Because biomarkers
available for calibration are limited, most investigators use self-reports (e.g.,
24-hour recalls (24HRs)) as the reference instrument. We evaluated the
performance of 24HRs as reference instruments for calibrating food frequency
questionnaires (FFQs), using data from the Validation Studies Pooling Project,
comprising 5 large validation studies using recovery biomarkers. Using 24HRs as
reference instruments, we estimated attenuation factors, correlations with truth,
and calibration equations for FFQ-reported intakes of energy and for protein,
potassium, and sodium and their densities, and we compared them with values
derived using biomarkers. Based on 24HRs, FFQ attenuation factors were
substantially overestimated for energy and sodium intakes, less for protein and
potassium, and minimally for nutrient densities. FFQ correlations with truth,
based on 24HRs, were substantially overestimated for all dietary components.
Calibration equations did not capture dependencies on body mass index. We also
compared predicted bias in estimated relative risks adjusted using 24HRs as
reference instruments with bias when making no adjustment. In disease models with
energy and 1 or more nutrient intakes, predicted bias in estimated nutrient
relative risks was reduced on average, but bias in the energy risk coefficient
was unchanged.
PMID- 28402489
TI - Social and asocial prefrontal cortex neurons: a new look at social facilitation
and the social brain.
AB - A fundamental aspect of behavior in many animal species is 'social facilitation',
the positive effect of the mere presence of conspecifics on performance. To date,
the neuronal counterpart of this ubiquitous phenomenon is unknown. We recorded
the activity of single neurons from two prefrontal cortex regions, the
dorsolateral part and the anterior cingulate cortex in monkeys as they performed
a visuomotor task, either in the presence of a conspecific (Presence condition)
or alone. Monkeys performed better in the presence condition than alone (social
facilitation), and analyses of outcome-related activity of 342 prefrontal neurons
revealed that most of them (86%) were sensitive to the performance context. Two
populations of neurons were discovered: 'social neurons', preferentially active
under social presence and 'asocial neurons', preferentially active under social
isolation. The activity of these neurons correlated positively with performance
only in their preferred context (social neurons under social presence; asocial
neurons under social isolation), thereby providing a potential neuronal mechanism
of social facilitation. More generally, the fact that identical tasks recruited
either social or asocial neurons depending on the presence or absence of a
conspecific also brings a new look at the social brain hypothesis.
PMID- 28402491
TI - Matched Comparison of Flow Diversion and Coiling in Small, Noncomplex
Intracranial Aneurysms.
AB - BACKGROUND: Flow diversion is typically reserved for large, giant, or
morphologically complex aneurysms. Coiling remains a first-line treatment for
small, morphologically simple aneurysms. OBJECTIVE: To compare coiling and flow
diversion in small, uncomplicated intracranial aneurysms (typically amenable to
coiling). METHODS: Forty patients treated with the pipeline embolization device
(PED) for small (<10 mm), morphologically simple aneurysms that would have also
been amenable to coiling were identified. These patients were matched in a 1:1
fashion with 40 patients with comparable aneurysms treated with coiling. Matching
was based on age, gender, aneurysm size, and aneurysm morphology. RESULTS: The 2
groups were comparable with regard to baseline characteristics including age,
gender, and aneurysm size. The complication rate did not differ between the 2
groups (2.5% with coiling vs 5% with PED; P = .6). Multivariate analysis did not
identify any predictor of complications. Complete occlusion (100%) at follow-up
was significantly higher in patients treated with PED (70%) than coiling (47.5%,
P = .04). In multivariate analysis, treatment with PED predicted aneurysm
obliteration ( P = .04). A significantly higher proportion of coiled patients
(32.5%) required retreatment compared with flow diversion (5%, P = .003). In
multivariate analysis, coiling predicted retreatment ( P = .006). All patients
achieved a favorable outcome (modified Rankin Scale: 0-2) regardless of group.
CONCLUSION: This matched analysis suggests that flow diversion provides higher
occlusion rates, lower retreatment rates, and no additional morbidity compared
with coiling in small, simple aneurysms amenable to both techniques. These
results suggest a potential benefit for flow diversion over coiling even in
small, uncomplicated aneurysms.
PMID- 28402490
TI - Attraction of Cerambycid Beetles to Their Aggregation-Sex Pheromones Is
Influenced by Volatiles From Host Plants of Their Larvae.
AB - Here, we describe a field experiment that tested for attraction of cerambycid
beetles to odors from angiosperm hosts, and whether plant volatiles also serve to
enhance attraction of beetles to their aggregation-sex pheromones. Traps were
baited with a blend of synthesized chemicals that are common pheromone components
of species in the subfamilies Cerambycinae and Lamiinae. The source of plant
volatiles was chipped wood from trees of three angiosperm species, as well as
from one nonhost, gymnosperm species. Bioassays were conducted in wooded areas of
east-central Illinois. Traps were baited with the pheromone blend alone, the
blend + wood chips from one tree species, wood chips alone, or a solvent control
lure. Seven species of cerambycids were significantly attracted to the pheromone
blend, with or without wood chips. In two cases, wood chips from angiosperms
appeared to enhance attraction to pheromones, whereas they inhibited attraction
in another three cases. Pine chips did not strongly influence attraction of any
species. Overall, our results suggest that host plant volatiles from wood chips
may improve trap catch with synthesized pheromones for some cerambycid species,
but the effect is not general, necessitating case-by-case testing to determine
how individual target species are affected.
PMID- 28402492
TI - Predicting Transport of 3,5,6-Trichloro-2-Pyridinol Into Saliva Using a
Combination Experimental and Computational Approach.
AB - A combination experimental and computational approach was developed to predict
chemical transport into saliva. A serous-acinar chemical transport assay was
established to measure chemical transport with nonphysiological (standard cell
culture medium) and physiological (using surrogate plasma and saliva medium)
conditions using 3,5,6-trichloro-2-pyridinol (TCPy) a metabolite of the pesticide
chlorpyrifos. High levels of TCPy protein binding were observed in cell culture
medium and rat plasma resulting in different TCPy transport behaviors in the 2
experimental conditions. In the nonphysiological transport experiment, TCPy
reached equilibrium at equivalent concentrations in apical and basolateral
chambers. At higher TCPy doses, increased unbound TCPy was observed, and TCPy
concentrations in apical and basolateral chambers reached equilibrium faster than
lower doses, suggesting only unbound TCPy is able to cross the cellular
monolayer. In the physiological experiment, TCPy transport was slower than
nonphysiological conditions, and equilibrium was achieved at different
concentrations in apical and basolateral chambers at a comparable ratio (0.034)
to what was previously measured in rats dosed with TCPy (saliva:blood ratio:
0.049). A cellular transport computational model was developed based on TCPy
protein binding kinetics and simulated all transport experiments reasonably well
using different permeability coefficients for the 2 experimental conditions (1.14
vs 0.4 cm/h for nonphysiological and physiological experiments, respectively).
The computational model was integrated into a physiologically based
pharmacokinetic model and accurately predicted TCPy concentrations in saliva of
rats dosed with TCPy. Overall, this study demonstrates an approach to predict
chemical transport in saliva, potentially increasing the utility of salivary
biomonitoring in the future.
PMID- 28402493
TI - CD30+ T Cells in Late Seroma May Not Be Diagnostic of Breast Implant-Associated
Anaplastic Large Cell Lymphoma.
AB - : The objective was to analyze and discuss the implications of a nonmalignant
CD30+ late seroma. Methods included collection of seroma fluid and peripheral
blood from a patient with a late seroma 22 years after initial breast
reconstruction. A panel of 24 monoclonal antibodies was used to detect T-cell
receptor Vbeta regions present on ~70% of normal human peripheral blood T
lymphocytes. Flow cytometry gated on CD3+ and CD30+ activated T lymphocytes.
Cytospins were used to inspect the morphology of the T lymphocytes. Results from
the seroma fluid cytology revealed a spectrum of activated T lymphocytes as seen
in the blood of patients with immune disorders such as infectious mononucleosis.
Cells were judged to be nonmalignant by routine pathology. Flow cytometry
revealed >23% of CD3+ T lymphocytes belonged to an expanded T-cell family
expressing TCRVbeta13.2. Most Vbeta13.2 cells expressed T-cell activation antigen
CD30 indicating that CD30 is not restricted to anaplastic large cell lymphoma
(ALCL) in seroma fluids. A smaller expanded population of CD30+ T lymphocytes
expressing TCRVbeta 13.2 was detected in the blood. In conclusion, in this index
case, an expanded population of CD30+ activated T lymphocytes was detected in
seroma fluid surrounding a textured breast implant as well as in peripheral
blood, consistent with a local and systemic immune response. The demonstration of
an expanded CD30+ T-cell population in a polyclonal background suggests a
possible role for bacterial superantigens as a pathogenic factor. These data
further suggest that breast implant-associated anaplastic large cell lymphoma
(BIA-ALCL) may be the end stage of a CD30+ T-cell lymphoproliferative disorder.
LEVEL OF EVIDENCE: 5.
PMID- 28402494
TI - School Self-Concept in Adolescents With Chronic Pain.
AB - Objective: This study investigated school self-efficacy and sense of school
membership (collectively "school self-concept") as potential influences on
impaired school function among adolescents with chronic pain, including
comparison of adolescents with primary pain to those with disease-based pain and
pain-free peers. Methods: In all, 264 adolescents (12-17 years old) with primary
pain conditions, juvenile idiopathic arthritis, or no pain completed measures of
functional disability, school functioning, pain characteristics, and school self
concept, the Self-Efficacy Questionnaire for School Situations (SEQ-SS), and
Psychological Sense of School Membership (PSSM). Results: Both the SEQ-SS and
PSSM demonstrated reliability and some validity, with the SEQ-SS more strongly
supported. As a group, adolescents with primary pain conditions reported poorer
school self-concept. School self-efficacy, but not school belongingness,
predicted school functioning later in the school year. Conclusions: School self
concept, especially as assessed with the SEQ-SS, is relevant and important to
assess when addressing school functioning in youth with chronic pain.
PMID- 28402495
TI - Analysis of aneuploid lines of bread wheat to map chromosomal locations of genes
controlling root hair length.
AB - Background and Aims: Long root hairs enable the efficient uptake of poorly mobile
nutrients such as phosphorus. Mapping the chromosomal locations of genes that
control root hair length can help exploit the natural variation within crops to
develop improved cultivars. Genetic stocks of the wheat cultivar 'Chinese Spring'
were used to map genes that control root hair length. Methods: Aneuploid stocks
of 'Chinese Spring' were screened using a rapid method based on rhizosheath size
and then selected lines were assayed for root hair length to identify chromosomes
harbouring genes controlling root hair length. A series of lines with various
fractional deletions of candidate chromosomes were then screened to map the root
hair loci more accurately. A line with a deletion in chromosome 5A was analysed
with a 90 000 single nucleotide polymorphism (SNP) array. The phosphorus
acquisition efficiency (PAE) of one deletion line was compared with that of
euploid 'Chinese Spring' by growing the seedlings in pots at low and luxury
phosphorus supplies. Key Results: Chromosomes 1A, 1D and 5A were found to harbour
genes controlling root hair length. The 90 000 SNP array identified two candidate
genes controlling root hair length located on chromosome 5A. The line with a
deletion in chromosome 5A had root hairs that were approx. 20 % shorter than
euploid 'Chinese Spring', but this was insufficient to reduce its PAE.
Conclusions: A rapid screen for rhizosheath size enabled chromosomal regions
controlling root hair length to be mapped in the wheat cultivar 'Chinese Spring'
and subsequent analysis with an SNP array identified candidate genes controlling
root hair length. The difference in root hair length between euploid 'Chinese
Spring' and a deletion line identified in the rapid screen was still apparent,
albeit attenuated, when the seedlings were grown on a fully fertilized soil.
PMID- 28402497
TI - Systematic Review of Safety and Cost-Effectiveness of Venous Thromboembolism
Prophylaxis Strategies in Patients Undergoing Craniotomy for Brain Tumor.
AB - BACKGROUND: Studies have evaluated various strategies to prevent venous
thromboembolism (VTE) in neuro-oncology patients, without consensus. OBJECTIVE:
To perform a systematic review with cost-effectiveness analysis (CEA) of various
prophylaxis strategies in tumor patients undergoing craniotomy to determine the
safest and most cost-effective prophylaxis regimen. METHODS: A literature search
was conducted for VTE prophylaxis in brain tumor patients. Articles reporting the
type of surgery, choice of VTE prophylaxis, and outcomes were included. Safety of
prophylaxis strategies was determined by measuring rates of VTE and intracranial
hemorrhage. Cost estimates were collected based on institutional data and
existing literature. CEA was performed at 30 d after craniotomy, comparing the
following strategies: mechanical prophylaxis (MP), low molecular weight heparin
with MP (MP+LMWH), and unfractionated heparin with MP (MP+UFH) to prevent
symptomatic VTE. All costs were reported in 2016 US dollars. RESULTS: A total of
34 studies were reviewed (8 studies evaluated LMWH, 12 for MP, and 7 for UFH
individually or in combination; 4 studies used LMWH and UFH preoperatively).
Overall probability of VTE was 1.49% (95% confidence interval (CI) 0.42-3.72) for
MP+UFH, 2.72% [95% CI 1.23-5.15] for MP+LMWH, and 2.59% (95% CI 1.31-4.58) for
MP, which were not statistically significant. Compared to a control of MP alone,
the number needed to treat for MP+UFH is 91 and 769 for MP+LMWH. The risk of
intracranial hemorrhage was 0.26% (95% CI 0.01-1.34) for MP, 0.74% (95% CI 0.09
2.61) for MP+UFH, and 2.72% (95% CI 1.23-5.15) for MP+LMWH, which were also not
statistically significant. Compared to MP, the number needed to harm for MP+UFH
was 208 and for MP+LMWH was 41. Fifteen studies were included in the final CEA.
The estimated cost of treatment was $127.47 for MP, $142.20 for MP+UFH, and
$169.40 for MP+LMWH. The average cost per quality-adjusted life-year for
different strategies was $284.14 for MP+UFH, $338.39 for MP, and $722.87 for
MP+LMWH. CONCLUSION: Although MP+LMWH is frequently considered the optimal
prophylaxis for VTE risk reduction, our model suggests that MP+UFH is the safest
and most cost-effective measure to balance VTE and hemorrhage risks in brain
tumor patients at lower risk of hemorrhage. MP+LMWH may be more effective for
patients at higher risk of VTE.
PMID- 28402496
TI - Mortality selection in a genetic sample and implications for association studies.
AB - Background: Mortality selection occurs when a non-random subset of a population
of interest has died before data collection and is unobserved in the data.
Mortality selection is of general concern in the social and health sciences, but
has received little attention in genetic epidemiology. We tested the hypothesis
that mortality selection may bias genetic association estimates, using data from
the US-based Health and Retirement Study (HRS). Methods: We tested mortality
selection into the HRS genetic database by comparing HRS respondents who survive
until genetic data collection in 2006 with those who do not. We next modelled
mortality selection on demographic, health and social characteristics to
calculate mortality selection probability weights. We analysed polygenic score
associations with several traits before and after applying inverse-probability
weighting to account for mortality selection. We tested simple associations and
time-varying genetic associations (i.e. gene-by-cohort interactions). Results: We
observed mortality selection into the HRS genetic database on demographic, health
and social characteristics. Correction for mortality selection using inverse
probability weighting methods did not change simple association estimates.
However, using these methods did change estimates of gene-by-cohort interaction
effects. Correction for mortality selection changed gene-by-cohort interaction
estimates in the opposite direction from increased mortality selection based on
analysis of HRS respondents surviving through 2012. Conclusions: Mortality
selection may bias estimates of gene-by-cohort interaction effects. Analyses of
HRS data can adjust for mortality selection associated with observables by
including probability weights. Mortality selection is a potential confounder of
genetic association studies, but the magnitude of confounding varies by trait.
PMID- 28402498
TI - Oviposition Strategies of Florida Culex (Melanoconion) Mosquitoes.
AB - In the genus Culex, oviposition is often generalized as laying floating egg rafts
directly on the surface of the water, as reported for arbovirus vectors Culex
pipiens L. and Culex tarsalis Coquillett, both members of subgenus Culex. The
current work reports on investigations of exceptions to this strategy by species
of Melanoconion, a diverse and mostly tropical subgenus of Culex, with many
arbovirus vectors. Wild gravid females from Vero Beach, FL, were introduced into
outdoor cages with open water, partially covered water, and emergent solid
structures for oviposition. Three species, Culex cedecei Stone and Hair, Culex
iolambdis Dyar, and Culex pilosus Dyar and Knab laid vast majorities (80-100%) of
egg clusters attached to solid surfaces, although at different heights and
angles, while Culex atratus Theobald laid floating egg clusters (100%) directly
on the water. When offered mud, open water, and woody material, Cx. iolambdis
laid 86% of clusters on nearly vertical surfaces of mangrove rootlets. Culex
iolambdis eggs laid on solid surfaces hatched within 3-4 d or dried up without
hatching. Results suggest that Melanoconion species utilize a variety of
oviposition strategies, yet most species studied oviposit out of water. For some
species, such as Cx. pilosus, this is a strategy for diapause and desiccation
resistance, while for others, such as Cx. iolambdis, ovipositing above water may
protect eggs from predators or being flushed from larval habitat. A summary of
oviposition strategies in genus Culex shows that above-water oviposition is
widespread and that the Culex egg raft paradigm needs reassessment.
PMID- 28402499
TI - Structural basis for the D-stereoselectivity of human DNA polymerase beta.
AB - Nucleoside reverse transcriptase inhibitors (NRTIs) with L-stereochemistry have
long been an effective treatment for viral infections because of the strong D
stereoselectivity exhibited by human DNA polymerases relative to viral reverse
transcriptases. The D-stereoselectivity of DNA polymerases has only recently been
explored structurally and all three DNA polymerases studied to date have
demonstrated unique stereochemical selection mechanisms. Here, we have solved
structures of human DNA polymerase beta (hPolbeta), in complex with single
nucleotide gapped DNA and L-nucleotides and performed pre-steady-state kinetic
analysis to determine the D-stereoselectivity mechanism of hPolbeta. Beyond a
similar 180 degrees rotation of the L-nucleotide ribose ring seen in other
studies, the pre-catalytic ternary crystal structures of hPolbeta, DNA and L-dCTP
or the triphosphate forms of antiviral drugs lamivudine ((-)3TC-TP) and
emtricitabine ((-)FTC-TP) provide little structural evidence to suggest that
hPolbeta follows the previously characterized mechanisms of D-stereoselectivity.
Instead, hPolbeta discriminates against L-stereochemistry through accumulation of
several active site rearrangements that lead to a decreased nucleotide binding
affinity and incorporation rate. The two NRTIs escape some of the active site
selection through the base and sugar modifications but are selected against
through the inability of hPolbeta to complete thumb domain closure.
PMID- 28402500
TI - Evaluation of the AID carbapenemase line probe assay for rapid detection and
identification of carbapenemase genes in Gram-negative bacilli.
AB - Objectives: This study evaluated the AID carbapenemase line probe assay (LPA) for
the detection and identification of carbapenem resistance genes in
Enterobacteriaceae and other Gram-negative bacilli (GNB) using bacterial cultures
and DNA extracts directly from patient urine samples. Methods: The AID
carbapenemase LPA detects 13 different carbapenemase genes. Test probe accuracy
was verified for using clinical Enterobacteriaceae isolates harbouring bla KPC ,
bla VIM , bla NDM , bla GIM , bla AIM , bla SPM , bla IMP and bla OXA-48 and a
well-characterized set of Escherichia coli DH5alpha strains transformed with the
vector plasmid pUC57- kan harbouring bla BIC , bla SIM , bla DIM , bla IMI-3 ,
bla IMI-1 and bla NMC-A . Sensitivity and specificity was determined by testing
151 clinical GNB strains previously characterized for the production of
carbapenemase activity and carbapenemase genes. Direct detection of carbapenemase
genes using the LPA was determined using 299 clinical urine specimens. Analytical
sensitivity for detection in urine was determined by testing serial dilutions of
bla KPC and bla NDM in clinical Klebsiella pneumoniae strains. Results: All
carbapenemase gene probes showed 100% accuracy without cross-reactions.
Sensitivity and specificity of the LPA using clinical isolates was 100% for each.
Analytical sensitivity for detection of bla KPC and bla NDM in urine was 10 1 -10
2 cfu. The LPA detected carbapenemase genes in 20 urines, which were confirmed in
12 samples by conventional multiplex PCR. Remarkably, 0 of the 20 urines grew
carbapenemase-suspicious GNB applying EUCAST recommendations. Conclusions: The
AID carbapenemase LPA is an accurate, sensitive and easy-to-use test for the
detection and identification of carbapenemase genes, which can readily be
implemented in any diagnostic laboratory.
PMID- 28402501
TI - The Use of a Binary Composite Endpoint and Sample Size Requirement: Influence of
Endpoints Overlap.
AB - Although composite endpoints (CE) are common in clinical trials, the impact of
the relationship between the components of a binary CE on the sample size
requirement (SSR) has not been addressed. We performed a computational study
considering 2 treatments and a CE with 2 components: the relevant endpoint (RE)
and the additional endpoint (AE). We assessed the strength of the components'
interrelation by the degree of relative overlap between them, which was
stratified into 5 groups. Within each stratum, SSR was computed for multiple
scenarios by varying the events proportion and the effect of the therapy. A lower
SSR using CE was defined as the best scenario for using the CE. In 25 of 66
scenarios the degree of relative overlap determined the benefit of using CE
instead of the RE. Adding an AE with greater effect than the RE leads to lower
SSR using the CE regardless of the AE proportion and the relative overlap. The
influence of overlapping decreases when the effect on RE increases. Adding an AE
with lower effect than the RE constitutes the most uncertain situation. In
summary, the interrelationship between CE components, assessed by the relative
overlap, can help to define the SSR in specific situations and it should be
considered for SSR computation.
PMID- 28402502
TI - Evaluation of human body irradiation caused by radionuclides deposited in the
filtration unit of gas mask.
AB - Radioactive aerosol particles represent a serious risk for people facing the
consequences of nuclear accident of any kind. The first responders to emergency
situation need to be protected by personal protective equipment which includes
radiation protection suit supplemented with gas mask. The purpose of this work is
to estimate the dose to the organs of responder's body as a result of
radionuclide deposition in the filtration unit of the gas mask. The problem was
analyzed using Monte Carlo simulations. The dose absorbed by different organs for
five representative radionuclides and the dose distribution over the responder's
body are presented in this paper. Based on presented MC simulations, we suggest a
method of evaluating the irradiation of the responder by the radionuclides
deposited in the filtration unit of the gas mask.
PMID- 28402504
TI - Erratum to: Improved 5-year prediction of all-cause mortality by coronary CT
angiography applying the CONFIRM score.
PMID- 28402503
TI - Poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in
human 18S rRNA maturation.
AB - The poly-A specific ribonuclease (PARN), initially characterized for its role in
mRNA catabolism, supports the processing of different types of non-coding RNAs
including telomerase RNA. Mutations in PARN are linked to dyskeratosis congenita
and pulmonary fibrosis. Here, we show that PARN is part of the enzymatic
machinery that matures the human 18S ribosomal RNA (rRNA). Consistent with its
nucleolar steady-state localization, PARN is required for 40S ribosomal subunit
production and co-purifies with 40S subunit precursors. Depletion of PARN or
expression of a catalytically-compromised PARN mutant results in accumulation of
3? extended 18S rRNA precursors. Analysis of these processing intermediates
reveals a defect in 3? to 5? trimming of the internal transcribed spacer 1 (ITS1)
region, subsequent to endonucleolytic cleavage at site E. Consistent with a
function of PARN in exonucleolytic trimming of 18S-E pre-rRNA, recombinant PARN
can process the corresponding ITS1 RNA fragment in vitro. Trimming of 18S-E pre
rRNA by PARN occurs in the nucleus, upstream of the final endonucleolytic
cleavage by the endonuclease NOB1 in the cytoplasm. These results identify PARN
as a new component of the ribosome biogenesis machinery in human cells. Defects
in ribosome biogenesis could therefore underlie the pathologies linked to
mutations in PARN.
PMID- 28402505
TI - DICER and ZRF1 contribute to chromatin decondensation during nucleotide excision
repair.
AB - Repair of damaged DNA relies on the recruitment of DNA repair factors in a well
orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by
chromatin remodelers to allow for binding of repair factors and for DNA repair to
occur. Recent studies have implicated members of the SWI/SNF and INO80 families
as well as PARP1 in nucleotide excision repair (NER). In this study, we report
that the endonuclease DICER is implicated in chromatin decondensation during NER.
In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated
manner. The H2A-ubiquitin binding protein ZRF1 and DICER together impact on the
chromatin conformation via PARP1. Moreover, DICER-mediated chromatin
decondensation is independent of its catalytic activity. Taken together, we
describe a novel function of DICER at chromatin and its interaction with the
ubiquitin signalling cascade during GG-NER.
PMID- 28402506
TI - Social identity shapes social valuation: evidence from prosocial behavior and
vicarious reward.
AB - People frequently engage in more prosocial behavior toward members of their own
groups, as compared to other groups. Such group-based prosociality may reflect
either strategic considerations concerning one's own future outcomes or intrinsic
value placed on the outcomes of in-group members. In a functional magnetic
resonance imaging experiment, we examined vicarious reward responses to
witnessing the monetary gains of in-group and out-group members, as well as
prosocial behavior towards both types of individuals. We found that individuals'
investment in their group-a motivational component of social identification
tracked the intensity of their responses in ventral striatum to in-group (vs out
group) members' rewards, as well as their tendency towards group-based
prosociality. Individuals with strong motivational investment in their group
preferred rewards for an in-group member, whereas individuals with low investment
preferred rewards for an out-group member. These findings suggest that the
motivational importance of social identity-beyond mere similarity to group
members-influences vicarious reward and prosocial behavior. More broadly, these
findings support a theoretical framework in which salient social identities can
influence neural representations of subjective value, and suggest that social
preferences can best be understood by examining the identity contexts in which
they unfold.
PMID- 28402507
TI - Thoughts About Disordered Thinking: Measuring and Quantifying the Laws of Order
and Disorder.
PMID- 28402508
TI - Preserved endothelial progenitor cell angiogenic activity in African American
essential hypertensive patients.
AB - Background: African American (AA) subjects with essential hypertension (EH) have
greater inflammation and cardiovascular complications than Caucasian EH. An
impaired endogenous cellular repair system may exacerbate vascular injury in
hypertension, yet whether these differ between AA EH and Caucasian EH remains
unknown. Vascular repair by circulating endothelial progenitor cells (EPCs) is
controlled by regulators of EPC mobilization, homing, adhesion and new vessel
formation, but can be hindered by various cytokines. We hypothesized that EPC
levels and function would be impaired in AA EH compared with Caucasian EH, in
association with increased levels of inflammatory mediators and EPC regulators.
Methods: CD34+/KDR+ EPCs were isolated from inferior vena cava and renal vein
blood samples of AA EH and Caucasian EH patients (n = 18 each) and from
peripheral veins of 17 healthy volunteers (HVs) and enumerated using fluorescence
activated cell sorting. Angiogenic function of late-outgrowth endothelial cells
expanded from these samples for 3 weeks was tested in vitro. Levels of
inflammatory mediators, angiogenic factors and EPC regulators were measured by
Luminex. Results: EPC levels were decreased in both AA and Caucasian EH compared
with HVs, whereas their late-outgrowth endothelial cell angiogenic function was
comparable. Levels of several inflammatory mediators were elevated in AA EH
compared with Caucasian EH and HVs. Contrarily, vascular endothelial growth
factor and its receptor-2 were lower. EPC levels inversely correlated with blood
pressure in all hypertensive patients and estimated glomerular filtration rate
with inflammatory mediators only in AA EH. Conclusions: Despite lower EPC
numbers, decreased vascular endothelial growth factor signaling and inflammation,
EPC function is preserved in AA EH compared with Caucasian EH and HVs, suggesting
compensatory mechanisms for vascular repair.
PMID- 28402509
TI - Identification of IS1R and IS10R elements inserted into ompk36 porin gene of two
multidrug-resistant Klebsiella pneumoniae hospital strains.
AB - Hospital Klebsiella pneumoniae strains (n = 196) were collected in 2012-16 from
the patients of a Moscow neurosurgical intensive care unit. Klebsiella pneumoniae
strains were multidrug-resistant and carried beta-lactamase genes blaSHV (97.4%
of strains), blaCTX-M (84.7%), blaTEM (56.1%), blaOXA-48-like (49.0%) and blaNDM
1 (one strain), class 1 integrons (43.4% of strains) and porin protein ompK36
gene (100% of strains). The ompK36 porin protein gene disruption by insertion
sequence (IS) elements and OmpK36 production loss in two strains were detected in
this study. Outer membrane proteins were isolated according to Carlone et al.
(Rapid microprocedure for isolating detergent-insoluble outer membrane proteins
from Haemophilus species. J Clin Microbiol 1986;24:330-2). The IS10R element
belonging to the IS4 family, IS10 group was detected at the position of the 41st
nucleotide of the ompK36 gene in K. pneumoniae strain KPB-2304K/15 (the first
report for a certain IS element in K. pneumoniae). The IS1R element belonging to
the IS1 family was identified at the position of the 86th nucleotide of the
ompK36 gene in the K. pneumoniae strain KPB-367K/15 (novel insertion site for IS1
element into ompK36 gene). DNA transfer of the intact ompK36 gene into the strain
KPB-367K/15 by vector plasmid restored OmpK36 porin protein production and
resulted in a decrease of imipenem minimal inhibitory concentration. Such data
confirm the importance of IS elements in ongoing multidrug-resistant evolution in
hospital Klebsiella.
PMID- 28402510
TI - Growth patterns of pulmonary metastases: should we adjust resection techniques to
primary histology and size?
AB - OBJECTIVES: Safety margins in pulmonary metastasectomy are not yet well defined.
We hypothesize that histological subtype, size of the lesion and local growth
characteristics must be taken into consideration during metastasectomy. This
study was conducted to examine and classify growth patterns at resection margins
and define the relationships between aggressive local growth, metastasis size and
local recurrence to direct metastasectomy. METHODS: Histologic sections of
pulmonary metastases were prospectively collected and haematoxylin-eosin stains
were systematically evaluated and classified by their pattern of lung tissue
infiltration. Logistic regression was used to model the association between the
subgroups of colorectal, renal cell and epithelial cancers and melanomas and
sarcomas. RESULTS: From 183 patients, 412 lung specimens were removed, which
contained 459 pulmonary metastases. We found that 58% of all lesions had
microscopic signs of aggressive local dissemination. The metastases showed
histology-specific patterns of local growth: sarcoma was associated with pleural
infiltration; colorectal metastases with interstitial spread and aerogenous
spread of floating cancer cell clusters; and melanoma with perivascular growth
and with lymph vessel involvement. Aggressive patterns of growth had an
increasing probability of around 3% for each additional millimetre of metastasis
diameter. Local intrapulmonary recurrence was significantly more common in
association with interstitial growth and pleural penetration as well as safety
margins <7 mm. CONCLUSIONS: Approximately 40% of all lung metastases have a
smooth surface and might be resected with small margins. Growth characteristics
within the lung differ with the histologic subtype and safety margins should
generally increase with the size of the metastasis.
PMID- 28402511
TI - Serotonergic modulation as a pharmacological modality in the treatment of Dravet
syndrome.
PMID- 28402512
TI - Defective trophoblast invasion underlies fetal growth restriction and
preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.
AB - STUDY QUESTION: What is the impact of chronic hypertension on placental
development, fetal growth and maternal outcome in the stroke-prone spontaneously
hypertensive rat (SHRSP)? SUMMARY ANSWER: SHRSP showed an impaired remodeling of
the spiral arteries and abnormal pattern of trophoblast invasion during
placentation, which were associated with subsequent maternal glomerular injury
and increased baseline hypertension as well as placental insufficiency and
asymmetric fetal growth restriction (FGR). WHAT IS KNOWN ALREADY: A hallmark in
the pathogenesis of preeclampsia (PE) is abnormal placentation with defective
remodeling of the spiral arteries preceding the onset of the maternal syndrome.
Pregnancies affected by chronic hypertension display an increased risk for PE,
often associated with poor maternal and fetal outcomes. However, the impact of
chronic hypertension on the placentation process as well as the nature of the
factors promoting the development of PE in pregnant hypertensive women remain
elusive. STUDY DESIGN, SIZE, DURATION: Timed pregnancies [n = 5] were established
by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls)
females with congenic males. Maternal systolic blood pressures (SBPs) were
recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail
cuff method. On selected dates, 24 h urine- and blood samples were collected, and
animals were euthanized for isolation of implantation sites and kidneys for
morphometrical analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 24 h
proteinuria and the albumin:creatinine ratio were used for evaluation of maternal
renal function. Renal injury was assessed on periodic acid Schiff, Masson's
trichrome and Sirius red stainings. Placental and fetal weights were recorded on
gestation day (GD)18 and GD20, followed by determination of fetal cephalization
indexes and developmental stage, according to the Witschi scale. Morphometric
analyses of placental development were conducted on hematoxylin-eosin stained
tissue sections collected on GD14 and GD18, and complemented with
immunohistochemical evaluation of isolectin B4 binding for assessment of
placental vascularization. Analyses of vascular wall alpha actin content,
perforin-positive natural killer (NK) cells and cytokeratin expression by
immunohistochemistry were used for evaluation of spiral artery remodeling and
trophoblast invasion. MAIN RESULTS AND THE ROLE OF CHANCE: SHRSP females
presented significantly increased SBP records from GD13 to GD17 (SBPGD13 = 183.9
+/- 3.9 mmHg, P < 0.005 versus baseline) and increased proteinuria at GD18 (P <
0.01 versus WKY). Histological examination of GD18 kidneys revealed glomerular
enlargement and mesangial matrix expansion, which were not evident in pregnant
WKY or age-matched virgin SHRSP. At GD20, SHRSP displayed a significant reduction
of placental mass (P < 0.01 versus WKY) and signs of placental insufficiency
(i.e. hypertrophy and reduced branching morphogenesis of the labyrinth layer),
associated with decreased offspring weights and increased cephalization index
(both P < 0.001 versus WKY) indicating asymmetric FGR. Notably, SHRSP placentas
displayed an incomplete remodeling of spiral arteries starting as early as GD14,
with luminal narrowing and reduced densities of perivascular NK cells followed by
decreased infiltration of endovascular trophoblasts at GD18. LARGE SCALE DATA:
n/a. LIMITATIONS, REASONS FOR CAUTION: A pitfall of the present study is the
differences in the blood pressure profiles between rats and humans (i.e. unlike
pregnancies affected by PE, blood pressure in SHRSP and other hypertensive rat
models decreases pre-delivery), which limits extrapolation of the results. WIDER
IMPLICATIONS OF THE FINDINGS: Our findings provide new insights on the role of
chronic hypertension as a risk factor for PE by interfering with early events
during the placentation process. The SHRSP strain represents an attractive model
for further studies aimed at addressing the relative contribution of intrinsic
(i.e. placental) and extrinsic (i.e. decidual/vascular) factors to defective
spiral artery remodeling in pregnancies affected by PE. STUDY FUNDING AND
COMPETING INTEREST(S): This work was supported by research grants from Fundacion
Florencio Fiorini to G.B., from Charite Stiftung to S.M.B. and University of
Buenos Aires (UBACyt) to J.T. The authors have no competing interests to declare.
PMID- 28402513
TI - INTERCOMPARISON ON THE MEASUREMENT OF THE QUANTITY PERSONAL DOSE EQUIVALENT
HP(10) IN PHOTON FIELDS. LINEARITY DEPENDENCE, LOWER LIMIT OF DETECTION AND
UNCERTAINTY IN MEASUREMENT OF DOSIMETRY SYSTEMS OF INDIVIDUAL MONITORING SERVICES
IN GABON AND GHANA.
AB - An inter-comparison study was conducted to assess the capability of dosimetry
systems of individual monitoring services (IMSs) in Gabon and Ghana to measure
personal dose equivalent Hp(10) in photon fields. The performance indicators
assessed were the lower limit of detection, linearity and uncertainty in
measurement. Monthly and quarterly recording levels were proposed with
corresponding values of 0.08 and 0.025 mSv, and 0.05 and 0.15 mSv for the TLD and
OSL systems, respectively. The linearity dependence of the dosimetry systems was
performed following the requirement given in the Standard IEC 62387 of the
International Electrotechnical Commission (IEC). The results obtained for the two
systems were satisfactory. The procedure followed for the uncertainty assessment
is the one given in the IEC technical report TR62461. The maximum relative
overall uncertainties, in absolute value, expressed in terms of Hp(10), for the
TL dosimetry system Harshaw 6600, are 44. 35% for true doses below 0.40 mSv and
36.33% for true doses >=0.40 mSv. For the OSL dosimetry system microStar, the
maximum relative overall uncertainties, in absolute value, are 52.17% for true
doses below 0.40 mSv and 37.43% for true doses >=0.40 mSv. These results are in
good agreement with the requirements for accuracy of the International Commission
on Radiological protection. When expressing the uncertainties in terms of
response, comparison with the IAEA requirements for overall accuracy showed that
the uncertainty results were also acceptable. The values of Hp(10) directly
measured by the two dosimetry systems showed a significant underestimation for
the Harshaw 6600 system, and a slight overestimation for the microStar system.
After correction for linearity of the measured doses, the two dosimetry systems
gave better and comparable results.
PMID- 28402514
TI - TAREAN: a computational tool for identification and characterization of satellite
DNA from unassembled short reads.
AB - Satellite DNA is one of the major classes of repetitive DNA, characterized by
tandemly arranged repeat copies that form contiguous arrays up to megabases in
length. This type of genomic organization makes satellite DNA difficult to
assemble, which hampers characterization of satellite sequences by computational
analysis of genomic contigs. Here, we present tandem repeat analyzer (TAREAN), a
novel computational pipeline that circumvents this problem by detecting satellite
repeats directly from unassembled short reads. The pipeline first employs graph
based sequence clustering to identify groups of reads that represent repetitive
elements. Putative satellite repeats are subsequently detected by the presence of
circular structures in their cluster graphs. Consensus sequences of repeat
monomers are then reconstructed from the most frequent k-mers obtained by
decomposing read sequences from corresponding clusters. The pipeline performance
was successfully validated by analyzing low-pass genome sequencing data from five
plant species where satellite DNA was previously experimentally characterized.
Moreover, novel satellite repeats were predicted for the genome of Vicia faba and
three of these repeats were verified by detecting their sequences on metaphase
chromosomes using fluorescence in situ hybridization.
PMID- 28402515
TI - Oxytocin differentially modulates pavlovian cue and context fear acquisition.
AB - Fear acquisition and extinction have been demonstrated as core mechanisms for the
development and maintenance of mental disorders, with different contributions of
processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a
prominent role in this context, as it has been shown to affect fear learning.
However, investigations have focused on cue conditioning, and fear extinction.
Its differential role for cue and context fear acquisition is still not known. In
a randomized, double-blind, placebo (PLC)-controlled design, we administered an
intranasal dose of OXT or PLC before the acquisition of cue and context fear
conditioning in healthy individuals (n = 52), and assessed brain responses, skin
conductance responses and self-reports (valence/arousal/contingency). OXT
compared with PLC significantly induced decreased responses in the nucleus
accumbens during early cue and context acquisition, and decreased responses of
the anterior cingulate cortex and insula during early as well as increased
hippocampal response during late context, but not cue acquisition. The OXT group
additionally showed significantly higher arousal in late cue and context
acquisition. OXT modulates various aspects of cue and context conditioning, which
is relevant from a mechanism-based perspective and might have implications for
the treatment of fear and anxiety.
PMID- 28402517
TI - Posterior Inferior Cerebellar Artery/Vertebral Artery Subarachnoid Hemorrhage: A
Comparison of Saccular vs Dissecting Aneurysms.
AB - BACKGROUND: Two distinct categories of aneurysms are described in relation to the
posterior inferior cerebellar artery (PICA) and vertebral artery (VA): saccular
(SA) and dissecting (DA) types. This distinction is often unrecognized because
abnormalities here are uncommon and most studies are small. OBJECTIVE: To
determine if there are any differences in the clinical presentation, in-hospital
course, or outcomes in patients with DA vs SA of the PICA or VA. METHODS: Thirty
eight patients with a VA or PICA aneurysm were identified from a departmental
subarachnoid hemorrhage database and categorized into DA or SA types.
Prospectively collected demographic and outcome data (length of stay, discharge
Glasgow Outcome Score) were supplemented by abstracting records for procedural
data (extraventricular drain [EVD], ventriculoperitoneal [VP] shunt,
tracheostomy, and nasogastric feeding). Univariate, binary logistic regression,
and Cox regression analysis was used to compare patients with SA vs DA. RESULTS:
Three aneurysms related to arteriovenous malformation were excluded. Five
patients were conservatively managed. Of the 30 treated cases, more patients with
a DA presented in poor grade (6/13 vs 2/17 SA; P = .035). More DA patients
required an EVD (85% vs 29%; P = .003), VP shunt (54% vs 6%; P = .003),
tracheostomy (46% vs 6%; P < .01), and nasogastric feeding (85% vs 35%; P =
.007). The median length of stay (41 vs 17 d, P < .001) was longer, and the age
and injury severity adjusted odds of discharge home were significantly lower in
the DA group (P = .008). Thirty-day mortality was not significantly different
(23% of DA vs 24% of SA; P = .2). CONCLUSION: The presentation, clinical course,
and outcomes differ in patients with DA vs SA of the PICA and VA.
PMID- 28402516
TI - Surgical Performance in Minimally Invasive Surgery Plus Recombinant Tissue
Plasminogen Activator for Intracerebral Hemorrhage Evacuation Phase III Clinical
Trial.
AB - BACKGROUND: Minimally invasive thrombolytic evacuation of intracerebral hematoma
is being investigated in the ongoing phase III clinical trial of Minimally
Invasive Surgery plus recombinant Tissue plasminogen activator for Intracerebral
hemorrhage Evacuation (MISTIE III). OBJECTIVE: To assess the accuracy of catheter
placement and efficacy of hematoma evacuation in relation to surgical approach
and surgeon experience. METHODS: We performed a trial midpoint interim assessment
of 123 cases that underwent the surgical procedure. Accuracy of catheter
placement was prospectively assessed by the trial Surgical Center based on
prearticulated criteria. Hematoma evacuation efficacy was evaluated based on
absolute volume reduction, percentage hematoma evacuation, and reaching the
target end-of-treatment volume of <15 mL. One of 3 surgical trajectories was
used: anterior (A), posterior (B), and lobar (C). Surgeons were classified based
on experience with the MISTIE procedure as prequalified, qualified with
probation, and fully qualified. RESULTS: The average hematoma volume was 49.7 mL
(range 20.0-124), and the mean evacuation rate was 71% (range 18.4%-99.8%). First
placed catheters were 58% in good position, 28% suboptimal (but suitable to
dose), and 14% poor (requiring repositioning). Posterior trajectory (B) was
associated with significantly higher rates of poor placement (35%, P = .01).
There was no significant difference in catheter placement accuracy among surgeons
of varying experience. Hematoma evacuation efficacy was not significantly
different among the 3 surgical approaches or different surgeons' experience.
CONCLUSION: Ongoing surgical education and quality monitoring in MISTIE III have
resulted in consistent rates of hematoma evacuation despite technical challenges
with the surgical approaches and among surgeons of varying experience.
PMID- 28402518
TI - Influence of coronary microcirculatory dysfunction on FFR calculation based on
computational fluid dynamics.
PMID- 28402519
TI - Response to the Commentary on Maes et al. "A Genetic Epidemiological Mega
Analysis of Smoking Initiation in Adolescents."
PMID- 28402521
TI - Efficiency of piezosurgery technique in miniscrew supported en-masse retraction:
a single-centre, randomized controlled trial.
AB - Background: Piezoelectric surgery is a newly introduced technique for rapid tooth
movement. However, the efficiency of this technique has not been investigated on
en-masse retraction cases yet. Objective: To investigate the efficiency of
piezosurgery technique in accelerating miniscrew supported en-masse retraction
and study the biological tissue response. In addition, to show if this technique
induces a difference in dental, skeletal and soft tissue changes on lateral
cephalograms, and in canine and molar rotations, besides intercanine and
intermolar widths on dental casts. Design, setting, participants: We conducted a
randomized, single-centred, parallel-group, controlled trial, requiring upper
right and left first premolar extractions on 30 patients above the minimum age of
14 years at the beginning of retraction. Interventions: Piezosurgery-assisted
versus conventional en-masse retraction anchored from miniscrews placed between
second premolars and first molars, bilaterally. Outcomes: The main outcome was
the en-masse retraction rate. Secondary outcomes were gingival crevicular fluid
(GCF) volume and GCF content of receptor activator of nuclear factor kappabeta
ligand (RANKL), changes regarding cephalometric and dental cast variables, and
miniscrew success rates. Randomization: Accomplished with opaque, sealed
envelopes. Blinding: Applicable for data assessment only. Recruitment: Commenced
in February 2013 and ended in October 2014. Results: Thirty-one patients were
included in the study and divided into 2 groups of piezosurgery (n = 16) and
control (n = 15). After 9.3 months of follow-up, no statistically significant
difference was observed between groups for neither retraction rates (P = 0.958)
nor GCF parameters (P > 0.05). Changes in lateral cephalometric and dental cast
variables, and miniscrew success rates did not show significant differences
either. Conclusion: Based on the results of this study, piezosurgery technique
was found to be ineffective in accelerating en-masse retraction, and promoting a
difference in the studied GCF parameters, skeletal and dental variables.
Registration: The trial was not registered. Protocol: The full protocol of this
PhD thesis study can be accessed from tez.yok.gov.tr. Funding: This work was
supported by Baskent University Research Fund. No conflict of interest was
declared.
PMID- 28402520
TI - A non-canonical multisubunit RNA polymerase encoded by the AR9 phage recognizes
the template strand of its uracil-containing promoters.
AB - AR9 is a giant Bacillus subtilis phage whose uracil-containing double-stranded
DNA genome encodes distant homologs of beta and beta' subunits of bacterial RNA
polymerase (RNAP). The products of these genes are thought to assemble into two
non-canonical multisubunit RNAPs - a virion RNAP (vRNAP) that is injected into
the host along with phage DNA to transcribe early phage genes, and a non-virion
RNAP (nvRNAP), which is synthesized during the infection and transcribes late
phage genes. We purified the AR9 nvRNAP from infected B. subtilis cells and
characterized its transcription activity in vitro. The AR9 nvRNAP requires
uracils rather than thymines at specific conserved positions of late viral
promoters. Uniquely, the nvRNAP recognizes the template strand of its promoters
and is capable of specific initiation of transcription from both double- and
single-stranded DNA. While the AR9 nvRNAP does not contain homologs of bacterial
RNAP alpha subunits, it contains, in addition to the beta and beta'-like
subunits, a phage protein gp226. The AR9 nvRNAP lacking gp226 is catalytically
active but unable to bind to promoter DNA. Thus, gp226 is required for promoter
recognition by the AR9 nvRNAP and may represent a new group of transcription
initiation factors.
PMID- 28402522
TI - Gene expression profiling of acute type A aortic dissection combined with in
vitro assessment.
AB - OBJECTIVES: The mechanisms underlying aortic dissection remain to be fully
elucidated. We aimed to identify key molecules driving dissection through gene
expression profiling achieved by microarray analysis and subsequent in vitro
experiments using human aortic endothelial cells (HAECs) and aortic vascular
smooth muscle cells (AoSMCs). METHODS: Total RNA, including microRNA (miRNA), was
isolated from the intima-media layer of dissected ascending aorta obtained
intraoperatively from acute type A aortic dissection (ATAAD) patients without
familial thoracic aortic disease (n = 8) and that of non-dissected ascending
aorta obtained from transplant donors (n = 9). Gene expression profiling was
performed with mRNA and miRNA microarrays, and results were confirmed by
quantitative polymerase chain reaction (qPCR). Target genes and miRNA were
identified by gene ontology analysis and a literature search. To reproduce the in
silico results, HAECs and AoSMCs were stimulated in vitro by upstream cytokines,
and expression of target genes was assessed by qPCR. RESULTS: Microarray analysis
revealed 1536 genes (3.6%, 1536/42 545 probes) and 41 miRNAs (3.0%, 41/1368
probes) that were differentially expressed in the ATAAD group (versus donor
group). The top 15 related pathways included regulation of inflammatory response,
growth factor activity and extracellular matrix. Gene ontology analysis
identified JAK2 (regulation of inflammatory response), PDGFA, TGFB1, VEGFA
(growth factor activity) and TIMP3, TIMP4, SERPINE1 (extracellular matrix) as the
target genes and miR-21-5p, a TIMP3 repressor, as target miRNA that interacts
with the target genes. Validation qPCR confirmed the altered expression of all 7
target genes and miR-21-5p in dissected aorta specimens (all genes, P < 0.05).
Ingenuity pathway analysis showed TNF-alpha and TGF-beta to be upstream cytokines
for the target genes. In vitro experiments showed these cytokines inhibit TIMP3
expression (P < 0.05) and enhance VEGFA expression (P < 0.01) in AoSMCs but not
HAECs. miR-21-5p expression increases in AoSMCs under TNF-alpha and TGF-beta
stimulation (fold change: 1.36; P = 0.011). CONCLUSIONS: Results of our novel
approach, integrating in vitro assessment into gene expression profiling,
implicated chronic inflammation characterized by MMP-TIMP dysregulation,
increased VEGFA expression, and TGF-beta signalling in the development of
dissection. Further investigation may reveal novel diagnostic biomarkers and
uncover the mechanism(s) underlying ATAAD.
PMID- 28402523
TI - Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and
mucosal protection and healing.
AB - Short-chain fatty acids (SCFAs), mainly acetate, propionate, and butyrate,
produced by microbial fermentation of undigested food substances are believed to
play a beneficial role in human gut health. Short-chain fatty acids influence
colonic health through various mechanisms. In vitro and ex vivo studies show that
SCFAs have anti-inflammatory and anticarcinogenic effects, play an important role
in maintaining metabolic homeostasis in colonocytes, and protect colonocytes from
external harm. Animal studies have found substantial positive effects of SCFAs or
dietary fiber on colonic disease, but convincing evidence in humans is lacking.
Most human intervention trials have been conducted in the context of inflammatory
bowel disease. Only a limited number of those trials are of high quality, showing
little or no favorable effect of SCFA treatment over placebo. Opportunities for
future research include exploring the use of combination therapies with anti
inflammatory drugs, prebiotics, or probiotics; the use of prodrugs in the setting
of carcinogenesis; or the direct application of SCFAs to improve mucosal healing
after colonic surgery.
PMID- 28402524
TI - The Effectiveness of an Intensive Interdisciplinary Pain Rehabilitation Program
in the Treatment of Post-Laminectomy Syndrome in Patients Who Have Failed Spinal
Cord Stimulation.
AB - Introduction: Post-laminectomy syndrome (PLS) patients who have previously
undergone spinal cord stimulation and failed to have significant improvement
create a unique challenge for ongoing pain management. We hypothesize that,
following successful completion of intensive, interdisciplinary pain
rehabilitation (IPR), this patient population can achieve a significant reduction
in pain, improvement in mood, functional levels, and self-efficacy. Materials and
methods: A retrospective chart review was conducted comparing the following for
patients prior to enrollment in the IPR program and upon completion: numeric
rating scale (NRS) pain scores; functional status via the six-minute walk test;
mood via the Center for Epidemiologic Studies Depression Scale (CES-D),
Multidimensional Pain Inventory (MPI) Life control scores and MPI Interference,
and the Pain Catastrophizing Scale (PCS); and self-efficacy via the Pain Self
Efficacy Questionnaire (PSEQ). Results: Forty-three patients met inclusion
criteria, with 17 males and 26 females and a mean age of 64 years. Patients
demonstrated a statistically significant increase in six-minute walk test
distance of 104 m, a decrease in average NRS pain score of 1.4 points, an
increase in average MPI life control by 8.3 points, a decrease average MPI
interference by 5.3 points, an increase in average Short Form-36 by 6.5 points,
an increase in average PCS by 4.4 points, and an increase in average PSEQ score
of 18.1. Their average mood via CES-D improved by 4.2 points. Conclusions:
Intensive, interdisciplinary pain rehabilitation provides an effective
therapeutic modality for patients with post-laminectomy syndrome who have failed
spinal cord stimulation by decreasing pain levels and by increasing functional
status and self-efficacy.
PMID- 28402525
TI - Antifungal mechanism of [RuIII(NH3)4catechol]+ complex on fluconazole-resistant
Candida tropicalis.
AB - Candidiasis, a major opportunistic mycosis caused by Candida sp., may comprise
life-threatening systemic infections. The incidence of non-albicans species is
rising, particularly in South America and they are frequently drug resistant,
causing unresponsive cases. Thus, novel antimycotic agents are required. Here we
tested the antifungal activity of [RuIII(NH3)4catechol]+ complex (RuCat),
approaching possible action mechanisms on fluconazole-resistant Candida
tropicalis. RuCat significantly (P < 0.05) inhibited the growth and viability of
C. tropicalis dose-dependently (IC50 20.3 MUM). Cytotoxicity of RuCat upon murine
splenocytes was lower (Selectivity Index = 16). Scanning electron microscopy
analysis showed pseudohyphae formation, yeast aggregation and surface damage.
RuCat-treated samples investigated by transmission electron microscopy showed
melanin granule trafficking to cell surfaces and extracellular milieu. Surface
adherent membrane fragments and extracellular debris were also observed. RuCat
treatment produced intense H2DCFDA labeling, indicating reactive oxygen species
(ROS) production which caused increased lipoperoxidation. ROS are involved in the
fungicidal effect as N-acetyl-L-cysteine completely restored cell viability.
Calcofluor White chitin staining suggests that 70 or 140 MUM RuCat treatment for
2 h affected cell-wall structure. PI labeling indicated necrotic cell death. The
present data indicate that RuCat triggers ROS production, lipoperoxidation and
cell surface damage, culminating in selective necrotic death of drug-resistant C.
tropicalis.
PMID- 28402526
TI - Diagnostic opportunism in BAH.
PMID- 28402527
TI - The relationship between selection, network connectivity, and regulatory
variation within a population of Capsella grandiora.
AB - Interactions between genes can have important consequences for how selection
shapes sequence variation at these genes. Specifically, genes that have
pleiotropic effects by affecting the expression level of many other genes may be
under stronger selective constraint. We used coexpression networks to measure
connectivity between genes and investigated the relationship between gene
connectivity and selection in a natural population of the plant Capsella
grandiora. We observed that network connectivity was negatively correlated with
genetic divergence due to stronger negative selection on highly-connected genes
even when controlling for variation in gene expression level. However, the
presence of local regulatory variation for a gene's expression level was also
associated with reduced negative selection and lower gene connectivity. While it
is difficult to disentangle the causal relationships between these factors, our
results show that both connectivity and local regulatory variation are important
factors for explaining variation in selection between genes.
PMID- 28402528
TI - Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an
Anteromedial Vertebrobasilar Artery Transposition Technique.
AB - BACKGROUND: Tortuous and dolichoectatic vertebrobasilar arteries can impinge on
the brainstem and cranial nerves to cause compression syndromes. Transposition
techniques are often required to decompress the brainstem with dolichoectatic
pathology. We describe our evolution of an anteromedial transposition technique
and its efficacy in decompressing the brainstem and relieving symptoms.
OBJECTIVE: To present the anteromedial vertebrobasilar artery transposition
technique for macrovascular decompression of the brainstem and cranial nerves.
METHODS: All patients who underwent vertebrobasilar artery transposition were
identified from the prospectively maintained database of the Vascular
Neurosurgery service, and their medical records were reviewed retrospectively.
The extent of arterial displacement was measured pre- and postoperatively on
imaging. RESULTS: Vertebrobasilar arterial transposition and macrovascular
decompression was performed in 12 patients. Evolution in technique was
characterized by gradual preference for the far-lateral approach, use of a sling
technique with muslin wrap, and an anteromedial direction of pull on the
vertebrobasilar artery with clip-assisted tethering to the clival dura. With this
technique, mean lateral displacement decreased from 6.6 mm in the first half of
the series to 3.8 mm in the last half of the series, and mean anterior
displacement increased from 0.8 to 2.5 mm, with corresponding increases in
satisfaction and relief of symptoms. CONCLUSION: Compressive dolichoectatic
pathology directed laterally into cranial nerves and posteriorly into the
brainstem can be corrected with anteromedial transposition towards the clivus.
Our technique accomplishes this anteromedial transposition from an inferolateral
surgical approach through the vagoaccessory triangle, with sling fixation to
clival dura using aneurysm clips.
PMID- 28402529
TI - Efficacy and safety of the second generation cryoballoon ablation for the
treatment of paroxysmal atrial fibrillation in patients over 75 years: a
comparison with a younger cohort.
AB - Aims: In this double centre, retrospective study, we aimed to analyse the 1-year
efficacy and safety of cryoballoon ablation (CB-A) in patients older than 75
years compared with those younger than 75-years old. Methods and results: Fifty
three consecutive patients aged 75 years or older with drug-resistant paroxysmal
AF (PAF) who underwent pulmonary vein isolation (PVI) by the means of second
generation CB-A, were compared with 106 patients aged <75 years. The mean age in
the study group (>75 years) was 78.19 +/- 2.7 years and 58.97 +/- 8.5 in the
control group. At 1-year follow-up the global success rate was 83.6% and did not
significantly differ between older (10/53) and younger patients (16/106) (81.1
vs. 84.9%, P = 0.54). Transient phrenic nerve palsy was the most common
complication which occurred in eight patients in the younger group and in three
in the older group (7.5 vs. 5.7%, respectively, P = 0.66). Conclusions: The
results of our study showed that CB-A for the treatment of PAF is a feasible and
safe procedure in elderly patients, with similar success and complications rates
when compared with a younger population.
PMID- 28402531
TI - Setting Tuberculosis Regimen Development on a Firm Foundation.
PMID- 28402530
TI - Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome.
AB - Context: Pituitary stalk interruption syndrome (PSIS) is characterized by a thin
or absent pituitary stalk usually in association with an ectopic posterior
pituitary and hypoplasia/aplasia of the anterior pituitary. Associated phenotypes
include varied ocular anomalies, hypoglycemia, micropenis/cryptorchidism, growth
failure, or combined pituitary hormone deficiencies. Although genetic causes have
been identified, they explain only around 5% of PSIS cases. Objective: To
identify genetic causes of PSIS by exome sequencing. Design: Exon enrichment was
performed using the Agilent SureSelect Human All Exon V4. Paired-end sequencing
was performed on the Illumina HiSeq2000 platform with an average sequencing
coverage of *50. Patients: Patients with unexplained PSIS were included in the
study. Results: In five cases of unexplained PSIS including two familial cases,
we identified a novel heterozygous frameshift and nonsense and missense mutations
in the ROBO1 gene (p.Ala977Glnfs*40, two affected sibs; p.Tyr1114Ter, sporadic
case, and p.Cys240Ser, affected child and paternal aunt) that controls embryonic
axon guidance, and branching in the nervous system. Interestingly, four of the
five cases of PSIS also presented with ocular anomalies, including hypermetropia
with strabismus as well as ptosis. Conclusions: These data suggest that mutations
in ROBO1 contribute to PSIS and associated ocular anomalies.
PMID- 28402532
TI - Strain-specific inhibition of the adherence of uropathogenic bacteria to bladder
cells by probiotic Lactobacillus spp.
AB - Urinary tract infections (UTIs), one of most common infections worldwide, face
high recurrence rates and increasing antimicrobial resistance. Probiotic
bacteria, especially of the genus Lactobacillus, are considered a promising
preventive and/or treatment therapy against UTIs. In order to elucidate the
mechanisms involved in these beneficial effects, we studied the impact of
different Lactobacillus strains (Lactobacillus salivarius UCM572, L. plantarum
CLC17 and L. acidophilus 01) in the adherence of reference and clinical
uropathogenic strains (Escherichia coli ATCC(r) 53503, E. coli 10791,
Enterococcus faecalis 04-1, En. faecalis 08-1 and Staphylococcus epidermidis 08
3) to T24 epithelial bladder cells. In general, the Lactobacillus strains with
previous in vivo evidence of beneficial effects against UTIs (L. salivarius
UCM572 and L. acidophilus 01) significantly inhibited the adherence of the five
uropathogens to T24 cells, displaying percentages of inhibition ranging between
22.2% and 43.9%, and between 16.5% and 53.7%, respectively. On the other hand, L.
plantarum CLC17, a strain with no expected effects on UTIs, showed almost
negligible anti-adherence effects.Therefore, these in vitro results suggest that
inhibition of the adherence of uropathogens to epithelial bladder cells may be
one of the mechanisms involved in the potential beneficial effects of probiotics
against UTIs in vivo.
PMID- 28402533
TI - Caregiver Perspectives About Using Antipsychotics and Other Medications for
Symptoms of Dementia.
AB - Background and Objectives: To avoid "chemical restraints," policies and
guidelines have been implemented to curb the use of medications for behavioral
and psychological symptoms of dementia (BPSD). Antipsychotics have been
particularly targeted because of their rare severe side effects. Consequently,
caregiver directed non-pharmacologic therapies have increased while medication
use for BPSD has diminished. Despite such initiatives, however, antipsychotics
continue to be prescribed "off-label" for roughly 20% of nursing home patients.
How caregivers impact management approaches and prescribing decisions for BPSD,
including antipsychotic use, is poorly understood. Aim: assesses experiences and
perceptions of family and nursing caregivers regarding factors influencing
medication decisions for BPSD. Research Design and Methods: Semi-structured
interviews, analyzed via template, immersion and crystallization, and thematic
development. Thirty-two participants from Northwestern Virginia representing five
groups of caregivers for dementia patients were interviewed: families of
community-dwelling, assisted living, and nursing home patients, and nurses from
the same assisted living/nursing home facilities. Results: Caregivers described
three major themes regarding medications: (a) Systemic barriers exist for non
pharmacologic BPSD therapies. (b) Medications have few barriers, and seem
generally effective and safe. (c) When non-pharmacologic measures fail,
medications, including antipsychotics, may be necessary and appropriate for
palliation of patient distress. Discussion and Implications: To further reduce
medications for BPSD, obstacles to services and alternative therapies must be
mitigated. Caregiver perceptions that medications are generally safe and
effective contribute to their continued use. Guidelines and policies for BPSD
management should incorporate the caregiver position that medications, including
antipsychotics, are sometimes justified and required to alleviate patient
suffering.
PMID- 28402535
TI - Sugar and artificially sweetened beverages linked to obesity: a systematic review
and meta-analysis.
AB - Background/Objectives: Artificial sweeteners are used widely to replace caloric
sugar as one of the strategies to lessen caloric intake. However, the association
between the risk of obesity and artificially sweetened soda consumption is
controversial. The objective of this meta-analysis aimed to assess the
association between consumption of sugar and artificially sweetened soda and
obesity. Methods: A literature search was performed using MEDLINE, EMBASE,
Cochrane Database of Systematic Reviews, and Cochrane Central Register of
Controlled Trials from inception through May 2015. Studies that reported relative
risks, odd ratios, or hazard ratios comparing the risk of obesity in patients
consuming either sugar or artificially sweetened soda vs. those who did not
consume soda were included. Pooled risk ratios (RRs) and 95% CI were calculated
using a random-effect, generic inverse variance method. Results: Eleven studies
were included in our analysis to assess the association between consumption of
sugar-sweetened soda and obesity. The pooled RR of obesity in patients consuming
sugar-sweetened soda was 1.18 (95% CI, 1.10-1.27). Three studies were included to
assess the association between consumption of artificially sweetened soda and
obesity. The pooled RR of obesity in patients consuming artificially sweetened
soda was 1.59 (95% CI, 1.22-2.08). Conclusions: Our study demonstrated a
significant association between sugar and artificially sweetened soda consumption
and obesity. This finding raises awareness and question of negative clinical
impact on both sugar and artificially sweetened soda and the risk of obesity.
PMID- 28402534
TI - An unpleasant emotional state reduces working memory capacity:
electrophysiological evidence.
AB - Emotional states can guide the actions and decisions we make in our everyday life
through their influence on cognitive processes such as working memory (WM). We
investigated the long-lasting interference that an unpleasant emotional state had
on goal-relevant WM representations from an electrophysiological perspective.
Participants performed a change detection task that was preceded by the
presentation of unpleasant or neutral task-irrelevant pictures in a blocked
fashion. We focused on the contralateral delay activity (CDA), an event-related
potential that is sensitive to the number of task-relevant items stored in WM. We
found that the asymptotic limit for the CDA amplitude was lower during the
unpleasant emotional state than during the neutral one; that is, an emotional
state was capable of reducing how many task-relevant items the participants could
hold in WM. Furthermore, both the individuals who experienced more intrusive
thoughts and those who were dispositionally anxious were more susceptible to the
influence of the emotional state. We provide evidence that an unpleasant
emotional state diminished visual WM for task-relevant items, particularly in
susceptible individuals. These results open new avenues to uncover the emotional
cognitive processing that underlies maladaptive WM representations and the role
of such processing in the development of mental illness.
PMID- 28402537
TI - Performance Assessment and Translation of Physiologically Based Pharmacokinetic
Models From acslX to Berkeley Madonna, MATLAB, and R Language: Oxytetracycline
and Gold Nanoparticles As Case Examples.
AB - Many physiologically based pharmacokinetic (PBPK) models for environmental
chemicals, drugs, and nanomaterials have been developed to aid risk and safety
assessments using acslX. However, acslX has been rendered sunset since November
2015. Alternative modeling tools and tutorials are needed for future PBPK
applications. This forum article aimed to: (1) demonstrate the performance of 4
PBPK modeling software packages (acslX, Berkeley Madonna, MATLAB, and R language)
tested using 2 existing models (oxytetracycline and gold nanoparticles); (2)
provide a tutorial of PBPK model code conversion from acslX to Berkeley Madonna,
MATLAB, and R language; (3) discuss the advantages and disadvantages of each
software package in the implementation of PBPK models in toxicology, and (4)
share our perspective about future direction in this field. Simulation results of
plasma/tissue concentrations/amounts of oxytetracycline and gold from different
models were compared visually and statistically with linear regression analyses.
Simulation results from the original models were correlated well with results
from the recoded models, with time-concentration/amount curves nearly
superimposable and determination coefficients of 0.86-1.00. Step-by-step
explanations of the recoding of the models in different software programs are
provided in the Supplementary Data. In summary, this article presents a tutorial
of PBPK model code conversion for a small molecule and a nanoparticle among 4
software packages, and a performance comparison of these software packages in
PBPK model implementation. This tutorial helps beginners learn PBPK modeling,
provides suggestions for selecting a suitable tool for future projects, and may
lead to the transition from acslX to alternative modeling tools.
PMID- 28402538
TI - Overall and abdominal obesity and incident aortic valve stenosis: two prospective
cohort studies.
AB - Aims: The aim of this study was to examine the association of overall and
abdominal obesity with aortic valve stenosis (AVS) incidence in two prospective
cohorts. Methods and results: We used data from the Cohort of Swedish Men and the
Swedish Mammography Cohort, involving 71 817 men and women who were free of
cardiovascular disease and had reported their anthropometric measures in 1997.
Aortic valve stenosis cases were ascertained through linkage with nationwide
registers on hospitalization and causes of death. Data were analysed using Cox
proportional hazards regression. During a mean follow-up of 15.3 years, 1297
incident AVS cases (771 in men; 526 in women) were ascertained. Both overall and
abdominal obesity, measured as body mass index (BMI) and waist circumference,
respectively, was associated with AVS incidence, with similar associations in men
and women. Compared with BMI 18.5-22.5 kg/m2, the multivariable hazard ratios
were 1.24 (95% confidence interval [CI] 1.05-1.48) for overweight (BMI 25.0-29.9
kg/m2) and 1.81 (95% CI 1.47-2.23) for obesity (BMI >=30 kg/m2). The hazard ratio
for substantially increased waist circumference (men: >=102 cm; women: >=88 cm)
compared with normal waist circumference (men: <94 cm; women: <80 cm) was 1.30
(95% CI 1.12-1.51). The proportion of AVS cases estimated to be attributed to
overweight and obesity combined (BMI >=25 kg/m2) was 10.8% (95% CI 5.2-16.4%).
Conclusion: These findings indicate that obesity is associated with an increased
risk of AVS and that a large proportion of the cases may be prevented if the
population maintained a healthy BMI.
PMID- 28402536
TI - The effect of constraining eye-contact during dynamic emotional face perception
an fMRI study.
AB - Eye-contact modifies how we perceive emotions and modulates activity in the
social brain network. Here, using fMRI, we demonstrate that adding a fixation
cross in the eye region of dynamic facial emotional stimuli significantly
increases activation in the social brain of healthy, neurotypical participants
when compared with activation for the exact same stimuli observed in a free
viewing mode. In addition, using PPI analysis, we show that the degree of
amygdala connectivity with the rest of the brain is enhanced for the constrained
view for all emotions tested except for fear, and that anxiety and alexithymia
modulate the strength of amygdala connectivity for each emotion differently.
Finally, we show that autistic traits have opposite effects on amygdala
connectivity for fearful and angry emotional expressions, suggesting that these
emotions should be treated separately in studies investigating facial emotion
processing.
PMID- 28402539
TI - Associating resting-state connectivity with trait impulsivity.
AB - Psychometric research has identified stable traits that predict inter-individual
differences in appetitive motivation and approach behavior. Behavioral Inhibition
System/Behavioral Activation System (BIS/BAS) scales have been developed to
quantitatively assess these traits. However, neural mechanisms corresponding to
the proposed constructs reflected in BIS/BAS are still poorly defined. The
ventral striatum (VS) and orbitofrontal cortex (OFC) are implicated in subserving
reward-related functions that are also associated with the BAS. In this study, we
examined whether functional connectivity between these regions predicts
components of these scales. We employed resting-state functional connectivity and
BIS/BAS scores assessed by a personality questionnaire. Participants completed a
resting state run and the Behavioral Inhibition and Activation Systems (BIS/BAS)
Questionnaire. Using resting-state BOLD, we assessed correlations between two
basal ganglia ROIs (caudate and putamen) and bilateral OFC ROIs, establishing
single subject connectivity summary scores. Summary scores were correlated with
components of BIS/BAS scores. Results demonstrate a novel correlation between BAS
fun seeking and resting-state connectivity between middle OFC and putamen,
implying that spontaneous synchrony between reward-processing regions may play a
role in defining personality characteristics related to impulsivity.
PMID- 28402540
TI - The Hepatic Protection Effects of Hepassocin in Hyperglycemic Crisis.
AB - Context: High glucose generates reactive oxygen species (ROS) and contributes to
glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional
damage to the liver. However, only a mild hepatic dysfunction was observed in
subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic
protective effect. Hepassocin is a hepatokine that modulates the proliferation
and metabolism of hepatocytes and also exerts protective activity in liver
injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction
remains unknown. Objective: To investigate the possible hepatic protection
effects of hepassocin in hyperglycemic crisis. Design, Setting, and Patients:
Plasma hepassocin concentrations and routine biochemistry were measured in 21
patients with hyperglycemic crisis before and after standard treatments. The
effects of hepassocin on hepatic functions were evaluated in streptozotocin
induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the
possible mechanisms regulating hepassocin expression. Results: Plasma hepassocin
concentrations decreased significantly in subjects with hyperglycemic crisis
after standard treatment accompanied by improved hepatic functions. Correction of
hyperglycemia in STZ mice also decreased the hepatic hepassocin expression.
Injection of recombinant hepassocin improved hepatic functions and histologic
changes and increased the expression of antioxidative stress proteins, including
superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin
expression through signal transducer and activator of transcription 3 and
hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin
increased SOD1 expression through an extracellular signal-regulated kinase 1/2
nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate
induced ROS production and improving cell viability. Conclusions: Increased
hepassocin secretion in hyperglycemic crisis might offset the deleterious effects
of hyperglycemia on hepatocytes.
PMID- 28402541
TI - A gene cluster at an unusual chromosomal location responsible for the novel O
antigen synthesis in Escherichia coli O62 by the ABC transporter-dependent
pathway.
AB - The O-antigen is a part of the outer membrane of Gram-negative bacteria and is
related to bacterial virulence. It is one of the most variable cell constituents,
and its structural diversity is almost entirely due to genetic variation of the O
antigen gene cluster. In this study, the O-antigen structure of Escherichia coli
O62 was elucidated by chemical analysis and nuclear magnetic resonance
spectroscopy, but showing not consistent with the O-antigen gene cluster between
conserved genes galF and gnd reported earlier. The complete genome of E. coli O62
was then sequenced and analyzed, and another O-antigen gene cluster was found and
characterized that correlated perfectly with the established O-antigen structure.
A deletion and complementation experiment confirmed the functionality of the
novel gene cluster and demonstrated that the O62-antigen is synthesized by the
ABC transporter-dependent system. To our knowledge, this is the first report that
the O-antigen gene cluster is positioned at a novel locus in E. coli. Comparative
analysis indicated that E. coli O62 likely originated from E. coli O68 via an IS
event resulting in the repression of the O68-antigen synthesis, followed by the
acquisition of a novel O-antigen gene cluster from Enterobacter aerogenes.
PMID- 28402543
TI - Courtney Q. Shah. Sex Ed, Segregated: The Quest for Sexual Knowledge in
Progressive-Era America.
PMID- 28402544
TI - Angiotensin-(1-7) in human follicular fluid correlates with oocyte maturation.
AB - STUDY QUESTION: Do angiotensin (Ang)-(1-7) levels in human ovarian follicular
fluid (FF) correlate with the number and proportion of mature oocytes obtained
for IVF? SUMMARY ANSWER: The present study shows for the first time that Ang-(1
7) levels in human FF correlate with the proportion of mature oocytes collected
upon ovarian stimulation for IVF. WHAT IS KNOWN ALREADY: Ang-(1-7) is an active
peptide of the renin-angiotensin system that stimulates oocyte maturation in
isolated rabbit and rat ovaries. However, its role in human ovulation remains
unexplored. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study
including 64 participants from a single IVF center. Sample size was calculated to
achieve a statistical power of 80% in detecting 20% differences in the proportion
of mature oocytes between groups. The participants were enrolled in the study
during six consecutive months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Plasma
samples were obtained from all subjects at Day 21 of the last menstrual cycle
before starting pituitary blockade and controlled ovarian stimulation (COS).
Plasma and FF samples were quickly mixed with a protease inhibitor cocktail and
stored at -80 degrees C. Ang-(1-7) was quantified in plasma and FF samples by a
highly sensitive and specific radioimmunoassay, which was preceded by solid phase
extraction, speed vacuum concentration and sample reconstitution in assay buffer.
FF Ang-(1-7) levels were stratified into tertiles and the patients of each
tertile were compared for COS/IVF outcomes using Kruskal-Wallis ANOVA. Multiple
regression analysis was used to adjust correlations for potential confounders.
The mRNA encoding for Mas, a receptor for Ang-(1-7), was investigated by real
time PCR in luteinized granulosa cells purified from the FF. MAIN RESULTS AND THE
ROLE OF CHANCE: There was a four-fold increase in plasma Ang-(1-7) after
ovulation induction (median 160.9 vs 41.4 pg/ml, P < 0.0001). FF Ang-(1-7) levels
were similar to (169.9 pg/ml) but did not correlate with plasma Ang-(1-7) levels
(r = -0.05, P = 0.665). Patients at the highest FF Ang-(1-7) tertile had a higher
proportion of mature oocytes compared to patients at the lower FF Ang-(1-7)
tertile (median 100% vs 70%, P < 0.01). There was a linear correlation between FF
Ang-(1-7) and the proportion of mature oocytes (r = 0.380, P < 0.01), which
remained significant after adjustment for age and duration of infertility (r =
0.447, P < 0.001). The luteinized granulosa cells expressed Mas receptor mRNA,
which was positively correlated to the number of mature oocytes in women with
more than three mature oocytes retrieved (r = 0.42, P < 0.01). LIMITATIONS,
REASONS FOR CAUTION: This is an observational study, therefore, no causal
relationship can be established between Ang-(1-7) and human oocyte maturation.
Mas protein expression was not quantified due to limited availability of
granulosa cells. WIDER IMPLICATIONS OF THE FINDINGS: Since this peptide promotes
oocyte maturation in other species, it deserves further investigation as a
potential maturation factor to human oocytes. STUDY FUNDING AND COMPETING
INTEREST(S): Research supported by Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de
Minas Gerais (FAPEMIG). The authors have nothing to disclose.
PMID- 28402542
TI - Positive affect predicts cerebral glucose metabolism in late middle-aged adults.
AB - Positive affect is associated with a number of health benefits; however, few
studies have examined the relationship between positive affect and cerebral
glucose metabolism, a key energy source for neuronal function and a possible
index of brain health. We sought to determine if positive affect was associated
with cerebral glucose metabolism in late middle-aged adults (n = 133).
Participants completed the positive affect subscale of the Center for
Epidemiological Studies Depression Scale at two time points over a two-year
period and underwent 18F-fluorodeoxyglucose-positron emission tomography
scanning. After controlling for age, sex, perceived health status, depressive
symptoms, anti-depressant use, family history of Alzheimer's disease, APOE
epsilon4 status and interval between visits, positive affect was associated with
greater cerebral glucose metabolism across para-/limbic, frontal, temporal and
parietal regions. Our findings provide evidence that positive affect in late
midlife is associated with greater brain health in regions involved in affective
processing and also known to be susceptible to early neuropathological processes.
The current findings may have implications for interventions aimed at increasing
positive affect to attenuate early neuropathological changes in at-risk
individuals.
PMID- 28402545
TI - ORIO (Online Resource for Integrative Omics): a web-based platform for rapid
integration of next generation sequencing data.
AB - Established and emerging next generation sequencing (NGS)-based technologies
allow for genome-wide interrogation of diverse biological processes. However,
accessibility of NGS data remains a problem, and few user-friendly resources
exist for integrative analysis of NGS data from different sources and
experimental techniques. Here, we present Online Resource for Integrative Omics
(ORIO; https://orio.niehs.nih.gov/), a web-based resource with an intuitive user
interface for rapid analysis and integration of NGS data. To use ORIO, the user
specifies NGS data of interest along with a list of genomic coordinates. Genomic
coordinates may be biologically relevant features from a variety of sources, such
as ChIP-seq peaks for a given protein or transcription start sites from known
gene models. ORIO first iteratively finds read coverage values at each genomic
feature for each NGS dataset. Data are then integrated using clustering-based
approaches, giving hierarchical relationships across NGS datasets and separating
individual genomic features into groups. In focusing its analysis on read
coverage, ORIO makes limited assumptions about the analyzed data; this allows the
tool to be applied across data from a variety of experiments and techniques.
Results from analysis are presented in dynamic displays alongside user-controlled
statistical tests, supporting rapid statistical validation of observed results.
We emphasize the versatility of ORIO through diverse examples, ranging from NGS
data quality control to characterization of enhancer regions and integration of
gene expression information. Easily accessible on a public web server, we
anticipate wide use of ORIO in genome-wide investigations by life scientists.
PMID- 28402546
TI - Aedes aegypti (Diptera: Culicidae) Abundance Model Improved With Relative
Humidity and Precipitation-Driven Egg Hatching.
AB - We propose an improved Aedes aegypti (L.) abundance model that takes into account
the effect of relative humidity (RH) on adult survival, as well as rainfall
triggered egg hatching. The model uses temperature-dependent development rates
described in the literature as well as documented estimates for mosquito survival
in environments with high RH, and for egg desiccation. We show that combining the
two additional components leads to better agreement with surveillance trap data
and with dengue incidence reports in various municipalities of Puerto Rico than
incorporating either alone or neither. Capitalizing on the positive association
between disease incidence and vector abundance, this improved model is therefore
useful to estimate incidence of Ae. aegypti-borne diseases in locations where the
vector is abundant year-round.
PMID- 28402547
TI - Perfluorododecanoic Acid Induces Cognitive Deficit in Adult Rats.
AB - The brain level of perfluorododecanoic acid (PFDoA) was compared with those of
perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in rats 9 days
after a single oral dose (50 mg/kg). The PFDoA level in the brain was 44.0 +/-
2.0 ug/g, which was higher than that in the serum (24.4 +/- 1.0 ug/ml). In
contrast, the concentrations of PFOA and PFDA in the brain were low (<0.8 and 4.7
+/- 0.4 ug/g, respectively), and less than one-tenth of those in the serum. Next,
to investigate the effects on brain function, the cognitive function alterations
of PFOA, PFDA, and PFDoA were estimated by the novel object recognition test 5-6
days after dosing. A significant decrease in the discrimination index was
observed in PFDoA-treated rats while no significant alteration was observed in
PFDA- and PFOA-treated rats. The effects of PFDoA were further assessed by other
behavioral tests. PFDoA-associated alteration was observed in the elevated-plus
maze test, but not in the Y-maze test, open-field test, and forced swim test. A
decrease in the discrimination index of the novel object recognition test was
dependent on the PFDoA dose and the PFDoA concentration in the brain. PFDoA
concentration in the brain was 28.6 +/- 2.6 ug/g 30 days after dosing, and a
decrease in discrimination index was observed. Taken together, these results
suggest that PFDoA distributes in the brain easier than PFOA and PFDA and causes
cognitive deficit.
PMID- 28402548
TI - The Acylated/Unacylated Ghrelin Ratio Is Similar in Patients With Acromegaly
During Different Treatment Regimens.
AB - Background: Data on plasma acylated ghrelin (AG) and unacylated ghrelin (UAG)
levels in acromegaly are limited. High AG/UAG ratios are linked with type 2
diabetes, obesity, and hyperphagia (e.g., in Prader-Willi syndrome). Objective:
To assess fasting plasma AG and UAG levels, and the AG/UAG ratio in acromegaly
patients receiving combination treatment of long-acting somatostatin analogs (LA
SSAs) and pegvisomant (PEGV; n = 60). We used as controls acromegaly patients
whose disease was controlled with PEGV monotherapy and medically naive patients
with active acromegaly. Methods: Fasting venous blood samples were collected and
directly stabilized to inhibit deacylation of AG. Plasma AG and UAG levels were
determined by double-antibody sandwich enzyme immunoassay, and the AG/UAG ratio
was calculated. Results: Plasma AG and UAG levels were significantly lower in
patients with acromegaly receiving combination treatment [median, interquartile
range (IQR): AG: 8.5 pg/mL, 2.9 to 21.1 pg/mL; UAG: 26.9 pg/mL, 11.2 to 42.1
pg/mL] compared with patients using PEGV alone [AG: 60.5 pg/mL (IQR, 58.8 to 77.4
pg/mL); UAG: 153.7 pg/mL (IQR, 127.3 to 196.0 pg/mL)] and medically naive
patients with acromegaly [AG: 24.0 pg/mL (IQR, 12.6 to 49.7 pg/mL); UAG: 56.3
pg/mL (IQR, 43.4 to 61.5 pg/mL)]. However, AG/UAG ratios were similar in all
groups. Conclusions: Although plasma AG and UAG are suppressed during combination
treatment with LA-SSAs and PEGV, the AG/UAG ratio remained similar. This shows
that SSAs decrease both AG and UAG levels, which suggests that they do not alter
metabolism significantly in acromegaly patients.
PMID- 28402549
TI - The link between perceived characteristics of neighbourhood green spaces and
adults' physical activity in UK cities: analysis of the EURO-URHIS 2 Study.
AB - Background: Urban dwellers represent half the world's population and are
increasing worldwide. Their health and behaviours are affected by the built
environment and green areas may play a major role in promoting physical activity,
thus decreasing the burden of chronic diseases, overweight and inactivity.
However, the availability of green areas may not guarantee healthy levels of
physical activity among the urban dwellers. It is therefore necessary to study
how the perceived characteristics of green areas affect physical activity.
Methods: Data from the EURO-URHIS 2 survey of residents of 13 cities across the
UK were analyzed and a multivariable model was created in order to assess the
association between their perceptions of the green areas in their neighbourhood
and their engagement in physical activity. Results were adjusted for age, gender
and other potential confounders. Results: Those who felt unable to engage in
active recreational activities in their local green spaces were significantly
less likely to carry out moderate physical exercise for at least 60 min per week
(adjusted OR: 0.50; 95% 0.37-0.68). Availability of green areas within walking
distance did not affect engagement in physical activity. Other characteristics
such as accessibility and safety may play an important role. Conclusion: This
study showed that the presence of green space may not itself encourage the
necessary preventative health behaviours to tackle physical inactivity in urban
populations. Development of more appropriate green spaces may be required.
Further research is needed to shed light on the types green spaces that are most
effective.
PMID- 28402550
TI - The Impact of Temperature and Body Size on Fundamental Flight Tone Variation in
the Mosquito Vector Aedes aegypti (Diptera: Culicidae): Implications for Acoustic
Lures.
AB - Aedes aegypti (L.) males use female flight tone as a means of mate localization.
By playing the sound of a flying female, males can be attracted to a trap to
monitor mosquito populations and the progress of transgenic male releases.
However, the female flight tone used to attract males needs to be optimized to
maximize trap effectiveness. The fundamental frequency of female flight tone
could be influenced by both body size and ambient temperature. However, no
analysis yet has considered both the effect of body size and temperature on
female flight tone of Ae. aegypti. Here, we present results for both these
factors by recording the sounds of free-flying and tethered females across
multiple temperature environments and with females reared for small, medium, and
large body sizes. We demonstrate that female fundamental frequency is highly
dependent on the environmental temperature, increasing ~8-13 Hz with each
degrees C gain. Body size and whether a female was tethered or free-flying did
not impact the relationship between frequency and temperature, although further
analysis is warranted. Our study highlights the importance of understanding the
relationship between flight tone and temperature, and will inform the design of
male mosquito traps.
PMID- 28402551
TI - A risk prediction score for acute kidney injury in the intensive care unit.
AB - Background: Acute kidney injury (AKI) is common in critically ill patients and is
associated with high morbidity and mortality. Early identification of high-risk
patients provides an opportunity to develop strategies for prevention, early
diagnosis and treatment of AKI. Methods: We undertook this multicenter
prospective cohort study to develop and validate a risk score for predicting AKI
in patients admitted to an intensive care unit (ICU). Patients were screened for
predictor variables within 48 h of ICU admission. Baseline and acute risk factors
were recorded at the time of screening and serum creatinine was measured daily
for up to 7 days. A risk score model for AKI was developed with multivariate
regression analysis combining baseline and acute risk factors in the development
cohort (573 patients) and the model was further evaluated on a test cohort (144
patients). Validation was performed on an independent prospective cohort of 1300
patients. The discriminative ability of the risk model was assessed by the area
under the receiver operating characteristic curve (AUROC) and model calibration
was evaluated by Hosmer-Lemeshow statistic. AKI was defined by the Kidney
Disease: Improving Global Outcomes criteria (absolute change of 0.3 mg/dL or
relative change of 50% from baseline serum creatinine in 48 h to 7 days,
respectively). Results: AKI developed in 754 (37.2%) patients. In the
multivariate model, chronic kidney disease, chronic liver disease, congestive
heart failure, hypertension, atherosclerotic coronary vascular disease, pH <=
7.30, nephrotoxin exposure, sepsis, mechanical ventilation and anemia were
identified as independent predictors of AKI and the AUROC for the model in the
test cohort was 0.79 [95% confidence interval (CI) 0.70-0.89]. On the external
validation cohort, the AUROC value was 0.81 (95% CI 0.78-0.83). The risk model
demonstrated good calibration in both cohorts. Positive and negative predictive
values for the optimal cutoff value of >= 5 points in test and validation cohorts
were 22.7 and 96.1% and 31.8 and 95.4%, respectively. Conclusions: A risk score
model integrating chronic comorbidities and acute events at ICU admission can
identify patients at high risk to develop AKI. This risk assessment tool could
help clinicians to stratify patients for primary prevention, surveillance and
early therapeutic intervention to improve care and outcomes of ICU patients.
PMID- 28402553
TI - In Reply: Surfer's Myelopathy: A Rare Form of Spinal Cord Infarction in Novice
Surfers: A Systematic Review.
PMID- 28402552
TI - Induced abortion.
AB - Abortion is common. Data on abortion rates are inexact but can be used to explore
trends. Globally, the estimated rate in the period 2010-2014 was 35 abortions per
1000 women (aged 15-44 years), five points less than the rate of 40 for the
period 1990-1994. Abortion laws vary around the world but are generally more
restrictive in developing countries. Restrictive laws do not necessarily deter
women from seeking abortion but often lead to unsafe practice with significant
mortality and morbidity. While a legal framework for abortion is a prerequisite
for availability, many laws, which are not evidence based, restrict availability
and delay access. Abortion should be available in the interests of public health
and any legal framework should be as permissive as possible in order to promote
access. In the absence of legal access, harm reduction strategies are needed to
reduce abortion-related mortality and morbidity. Abortion can be performed
surgically (in the first trimester, by manual or electric vacuum aspiration) or
with medication: both are safe and effective. Cervical priming facilitates
surgery and reduces the risk of incomplete abortion. Diagnosis of incomplete
abortion should be made on clinical grounds, not by ultrasound. Septic abortion
is a common cause of maternal death almost always following unsafe abortion and
thus largely preventable. While routine follow-up after abortion is unnecessary,
all women should be offered a contraceptive method immediately after the
abortion. This, together with improved education and other interventions, may
succeed in reducing unintended pregnancy.
PMID- 28402554
TI - Does how the patient feels matter? A prospective observational study of the
outcome of acutely ill medical patients who feel their condition has improved on
their first re-assessment after admission to hospital.
AB - Background: Although asking how a patient feels is the first enquiry most
clinicians make the value of the answer has never been examined in acutely ill
patients. Methods: Prospective observational study that compared the predictive
value of how well acutely ill medical patients felt after admission to a resource
poor sub-Saharan hospital with their mental alertness, mobility and vital signs.
Results: In total, 403 patients were studied. Patients who felt better when re
assessed 18.0 SD 9.1 h after admission to hospital were less likely to die in
hospital (OR 0.18 95% CI 0.08-0.43, P = 0.00001) and more likely to be
independent of others at discharge (OR 5.64 95% CI 3.04-10.47, P = 0.00001).
Feeling better was an independent predictor of in-hospital death along with vital
sign changes and gait stability, and an independent predictor of independence at
discharge along with vital sign changes, gait stability and female gender.
Conclusion: In this patient cohort a subjective feeling of improvement at the
first re-assessment after admission to hospital is a powerful independent
predictor of reduced in-hospital mortality.
PMID- 28402556
TI - Letter: Implications of Duty Hour Regulations From the Neurosurgery Resident
Perspective: Eliminate "Post-call" From Your Vocabulary.
PMID- 28402555
TI - Deregulation of the endometrial stromal cell secretome precedes embryo
implantation failure.
AB - STUDY QUESTION: Is implantation failure following ART associated with a perturbed
decidual response in endometrial stromal cells (EnSCs)? SUMMARY ANSWER: Dynamic
changes in the secretome of decidualizing EnSCs underpin the transition of a
hostile to a supportive endometrial microenvironment for embryo implantation;
perturbation in this transitional pathway prior to ART is associated with
implantation failure. WHAT IS KNOWN ALREADY: Implantation is the rate-limiting
step in ART, although the contribution of an aberrant endometrial
microenvironment in IVF failure remains ill defined. STUDY DESIGN, SIZE,
DURATION: In vitro characterization of the temporal changes in the decidual
response of primary EnSCs isolated prior to a successful or failed ART cycle. An
analysis of embryo responses to secreted cues from undifferentiated and
decidualizing EnSCs was performed. The primary clinical outcome of the study was
a positive urinary pregnancy test 14 days after embryo transfer.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary EnSCs were isolated from
endometrial biopsies obtained prior to IVF treatment and cryopreserved. EnSCs
from 10 pregnant and 10 non-pregnant patients were then thawed, expanded in
culture, subjected to clonogenic assays, and decidualized for either 2 or 8 days.
Transcript levels of decidual marker gene [prolactin (PRL), insulin-like growth
factor binding protein 1 (IGFBP1) and 11beta-hydroxysteroid dehydrogenase
(HSD11B1)] were analysed using real-time quantitative PCR and temporal secretome
changes of 45 cytokines, chemokines and growth factors were measured by multiplex
suspension bead immunoassay. The impact of the EnSC secretome on human blastocyst
development was scored morphologically; and embryo secretions in response to EnSC
cues analyzed by multiplex suspension bead immunoassay. MAIN RESULTS AND THE ROLE
OF CHANCE: Clonogenicity and induction of decidual marker genes were comparable
between EnSC cultures from pregnant and non-pregnant group groups (P > 0.05).
Analysis of 23 secreted factors revealed that successful implantation was
associated with co-ordinated secretome changes in decidualizing EnSCs, which were
most pronounced on Day 2 of differentiation: 17 differentially secreted proteins
on Day 2 of decidualization relative to undifferentiated (Day 0) EnSCs (P <
0.05); 11 differentially secreted proteins on Day 8 relative to Day 2 (P < 0.05);
and eight differentially secreted proteins on Day 8 relative to Day 0 (P < 0.05).
By contrast, failed implantation was associated with a disordered secretome
response. Blastocyst development was compromised when cultured for 24 h in medium
conditioned by undifferentiated EnSCs when compared to decidualizing EnSCs.
Analysis of the embryo microdroplets revealed that human blastocysts mount a
secretory cytokine response to soluble decidual factors produced during the early
(Day 2) but not late phase (Day 8) of differentiation. The embryo responses to
secreted factors from decidualizing EnSCs were comparable between the pregnant
and non-pregnant group (P > 0.05). LARGE SCALE DATA: Not applicable. LIMITATIONS,
REASONS FOR CAUTION: Although this study uses primary EnSCs and human embryos,
caution is warranted when extrapolating the results to the in vivo situation
because of the correlative nature of the study and limited sample size. WIDER
IMPLICATIONS OF THE FINDINGS: Our finding raises the prospect that endometrial
analysis prior to ART could minimize the risk of treatment failure. STUDY FUNDING
AND COMPETING INTEREST(S): This work was supported by funds from the Biomedical
Research Unit in Reproductive Health, a joint initiative of the University
Hospitals Coventry & Warwickshire NHS Trust and Warwick Medical School, the
University of Nottingham and Nurture Fertility, and the National Medical Research
Council, Singapore (NMRC/BNIG14NOV023), the "Instituut voor Innovatie door
Wetenschap en Technologie" (IWT, Flanders, Belgium), the "Fonds voor
Wetenschappelijk Onderzoek" (FWO, Flanders, Belgium) and the "Wetenschappelijk
Fonds Willy Gepts" (WFWG, UZ Brussel). The authors have declared that no conflict
of interest exists.
PMID- 28402557
TI - Effect of parathyroidectomy and cinacalcet on quality of life in patients with
end-stage renal disease-related hyperparathyroidism: a systematic review.
AB - Background: Patients with end-stage renal disease (ESRD) have a decreased quality
of life (QoL), which is attributable in part to ESRD-related hyperparathyroidism
(HPT). Both cinacalcet and parathyroidectomy (PTx) are treatments for advanced
HPT, but their effects on QoL are unclear. We performed a systematic review to
evaluate the impact of cinacalcet and PTx on QoL. Methods: A systematic
literature search was performed using PubMed and EMBASE databases to identify
relevant articles. The search was based on the following keywords:
'parathyroidectomy' or 'cinacalcet', 'secondary hyperparathyroidism' or 'renal
hyperparathyroidism' combined with 'quality of life' or 'SF-36' or
'symptomatology'. Only studies reporting on QoL at baseline and during follow-up
were included. QoL scores were extracted from the selected manuscripts and
weighted means were calculated. Due to a lack of available data on QoL
improvement in patients using cinacalcet, a meta-analysis could not be performed.
Results: In all, eight articles reached our inclusion criteria. Of this, five
articles reported the effect of PTx on QoL. All PTx studies were observational
and non-controlled. The physical component scores of the 36-item Medical Outcomes
Study Short-Form Health Survey increased significantly with a weighted mean of
35.5% (P < 0.05). Mental component scores increased with 13.7% (P < 0.05).
Parathyroidectomy assessment of symptom scores improved from 561 preoperatively
to 302 postoperatively (-259 points; -46.2%). Visual analogue scale scores
decreased significantly for skin itching (46.6%), joint pain (30.4%) and muscle
weakness (28.7%) (P < 0.05). Three studies on the effect of cinacalcet on QoL
were included, including one randomized controlled trial. None of these studies
showed significant improvement of physical component and mental component scores.
Conclusions: PTx improved QoL in patients treated for ESRD-related HPT, whereas
cinacalcet did not. The difference in impact between PTx and cinacalcet on QoL
has not been compared directly.
PMID- 28402558
TI - Effect of cadexomer iodine on the microbial load and diversity of chronic non
healing diabetic foot ulcers complicated by biofilm in vivo.
AB - Objectives: The performance of cadexomer iodine was determined against microbial
populations from chronic non-healing diabetic foot ulcers (DFUs) complicated by
biofilm in vivo , using molecular, microscopy and zymography methods. Methods:
Chronic non-healing DFUs due to suspected biofilm involvement were eligible for
enrolment. DNA sequencing and real-time quantitative PCR was used to determine
the microbial load and diversity of tissue punch biopsies obtained pre- and post
treatment. Scanning electron microscopy and/or fluorescence in situ hybridization
confirmed the presence or absence of biofilm. Zymography was used to determine
levels of wound proteases. Results: Seventeen participants were recruited over a
6 month period. Scanning electron microscopy and or fluorescence in situ
hybridization confirmed the presence of biofilm in all samples. Eleven
participants exhibited log 10 reductions in microbial load after treatment (range
1-2 log 10 ) in comparison with six patients who experienced <1 log 10 reduction
( P = 0.04). Samples were tested for levels of wound proteases pre- and post
treatment. Reductions in the microbial load correlated to reductions in wound
proteases pre- and post-treatment ( P = 0.03). Conclusions: To the best of our
knowledge, this study represents the first in vivo evidence, employing a range of
molecular and microscopy techniques, of the ability of cadexomer iodine to reduce
the microbial load of chronic non-healing DFUs complicated by biofilm. Further
analyses correlating log reductions to optimal duration of therapy and
improvements in clinical parameters of wound healing in a larger cohort are
required.
PMID- 28402559
TI - Occipital Nerve Stimulation Attenuates Neuronal Firing Response to Mechanical
Stimuli in the Ventral Posteromedial Thalamus of a Rodent Model of Chronic
Migraine.
AB - BACKGROUND: Chronic migraine (CM) is a highly debilitating disease, and many
patients remain refractory to medicinal therapy. Given the convergent nature of
neuronal networks in the ventral posteromedial nucleus (VPM) and the evidence of
sensitization of pain circuitry in this disease, we hypothesize CM rats will have
increased VPM neuronal firing, which can be attenuated using occipital nerve
stimulation (ONS). OBJECTIVE: To determine whether VPM firing frequency differs
between CM and sham rats, and whether ONS significantly alters firing rates
during the application of mechanical stimuli. METHODS: Fourteen male Sprague
Dawley rats were infused with inflammatory media once daily through an epidural
cannula for 2 wk to induce a CM state. Sham animals (n = 6) underwent cannula
surgery but received no inflammatory media. ONS electrodes were implanted
bilaterally and single-unit recordings were performed in the VPM of anesthetized
rats during mechanical stimulation of the face and forepaw in the presence and
absence of ONS. RESULTS: CM rats had significantly higher neuronal firing rates
(P < .001) and bursting activity (P < .01) in response to mechanical stimuli when
compared to shams. ONS significantly reduced neuronal firing in the VPM of CM
rats during the application of 0.8 g (P = .04), 4.0 g (P = .04), and 15.0 g (P =
.02) Von Frey filaments. ONS reduced bursting activity in CM rats during the 4.0
and 15 g filaments (P < .05). No significant changes in bursting activity or
firing frequency were noted in sham animals during ONS. CONCLUSION: We
demonstrate that neuronal spike frequencies and bursting activity in the VPM are
increased in an animal model of CM compared to shams. Our results suggest that
the mechanism of ONS may involve attenuation of neurons in the VPM of CM rats
during the application of mechanical stimuli.
PMID- 28402560
TI - Acute kidney injury electronic alerts in primary care - findings from a large
population cohort.
AB - Background: Electronic reporting of AKI has been used to aid early AKI
recognition although its relevance to CA-AKI and primary care has not been
described. Aims: We described the characteristics and clinical outcomes of
patients with CA-AKI, and AKI identified in primary care (PC-AKI) through AKI e
Alerts. Design: A prospective national cohort study was undertaken to collect
data on all e-alerts representing adult CA-AKI. Method: The study utilized the
biochemistry based AKI electronic (e)-alert system that is established across the
Welsh National Health Service. Results: 28.8% of the 22 723 CA-AKI e-alerts were
classified as PC-AKI. Ninety-day mortality was 24.0% and lower for PC-AKI vs. non
primary care (non-PC) CA-AKI. Hospitalization was 22.3% for PC-AKI and associated
with greater disease severity, higher mortality, but better renal outcomes (non
recovery: 18.1% vs. 21.6%; progression of pre-existing CKD: 40.5% vs. 58.3%).
49.1% of PC-AKI had a repeat test within 7 days, 42.5% between 7 and 90 days, and
8.4% was not repeated within 90 days. There was significantly more non-recovery
(24.0% vs. 17.9%) and progression of pre-existing CKD (63.3% vs. 47.0%) in
patients with late repeated measurement of renal function compared to those with
early repeated measurement of renal function. Conclusion: The data demonstrate
the clinical utility of AKI e-alerts in primary care. We recommend that a
clinical review, or referral together with a repeat measurement of renal function
within 7 days should be considered an appropriate response to AKI e-alerts in
primary care.
PMID- 28402562
TI - Medical Tourism, Medical Migration, and Global Justice: Implications for
Biosecurity in a Globalized World.
AB - We live in the age of globalization. In medicine, that globalization has brought
many benefits such as the diffusion of technology and the spread of health care
training, but it has also brought threats to biosecurity. This article examines
how medical tourism and medical migration pose risks to biosecurity. It also
argues that designing legal responses to these risks requires not only technical
competence but also a theory of global justice to guide that design.
PMID- 28402561
TI - The role of the default mode network in component processes underlying the
wandering mind.
AB - Experiences such as mind-wandering illustrate that cognition is not always
tethered to events in the here-and-now. Although converging evidence emphasises
the default mode network (DMN) in mind-wandering, its precise contribution
remains unclear. The DMN comprises cortical regions that are maximally distant
from primary sensory and motor cortex, a topological location that may support
the stimulus-independence of mind-wandering. The DMN is functionally
heterogeneous, comprising regions engaged by memory, social cognition and
planning; processes relevant to mind-wandering content. Our study examined the
relationships between: (i) individual differences in resting-state DMN
connectivity, (ii) performance on memory, social and planning tasks and (iii)
variability in spontaneous thought, to investigate whether the DMN is critical to
mind-wandering because it supports stimulus-independent cognition, memory
retrieval, or both. Individual variation in task performance modulated the
functional organization of the DMN: poor external engagement was linked to
stronger coupling between medial and dorsal subsystems, while decoupling of the
core from the cerebellum predicted reports of detailed memory retrieval. Both
patterns predicted off-task future thoughts. Consistent with predictions from
component process accounts of mind-wandering, our study suggests a 2-fold
involvement of the DMN: (i) it supports experiences that are unrelated to the
environment through strong coupling between its sub-systems; (ii) it allows
memory representations to form the basis of conscious experience.
PMID- 28402563
TI - In Reply: Guidelines for the Management of Severe Traumatic Brain Injury, Fourth
Edition.
PMID- 28402564
TI - Three decades of occupational individual monitoring at the University of Sao
Paulo.
AB - As the ionizing radiation to which workers are exposed is related to possible
harmful biological effect, its dose evaluation gains relevance. Although the
effects of low doses are still controversial, the radiation protection
authorities assume that any dose of ionizing radiation is potentially harmful to
the human health and adopt the linear non-threshold model for the dose-effect
relation. The Dosimetry Laboratory of the Institute of Physics of the University
of Sao Paulo performs the external individual monitoring of workers exposed to X-
and gamma-rays since 1981, with the technique of thermoluminescence. Currently,
~500 badges are provided to the university professionals mostly working in
research laboratories and hospitals. Data of individual annual dose equivalent
collected from 1995 to 2015 and the performance of the monitoring service are
presented in this paper.
PMID- 28402566
TI - Kartagener syndrome.
PMID- 28402565
TI - Impulsive-antisocial psychopathic traits linked to increased volume and
functional connectivity within prefrontal cortex.
AB - Psychopathy is a personality disorder characterized by callous lack of empathy,
impulsive antisocial behavior, and criminal recidivism. Studies of brain
structure and function in psychopathy have frequently identified abnormalities in
the prefrontal cortex. However, findings have not yet converged to yield a clear
relationship between specific subregions of prefrontal cortex and particular
psychopathic traits. We performed a multimodal neuroimaging study of prefrontal
cortex volume and functional connectivity in psychopathy, using a sample of adult
male prison inmates (N = 124). We conducted volumetric analyses in prefrontal
subregions, and subsequently assessed resting-state functional connectivity in
areas where volume was related to psychopathy severity. We found that overall
psychopathy severity and Factor 2 scores (which index the impulsive/antisocial
traits of psychopathy) were associated with larger prefrontal subregion volumes,
particularly in the medial orbitofrontal cortex and dorsolateral prefrontal
cortex. Furthermore, Factor 2 scores were also positively correlated with
functional connectivity between several areas of the prefrontal cortex. The
results were not attributable to age, race, IQ, substance use history, or brain
volume. Collectively, these findings provide evidence for co-localized increases
in prefrontal cortex volume and intra-prefrontal functional connectivity in
relation to impulsive/antisocial psychopathic traits.
PMID- 28402567
TI - Nonsense-mediated mRNA decay in Tetrahymena is EJC independent and requires a
protozoa-specific nuclease.
AB - Nonsense-mediated mRNA decay (NMD) is essential for removing premature
termination codon-containing transcripts from cells. Studying the NMD pathway in
model organisms can help to elucidate the NMD mechanism in humans and improve our
understanding of how this biologically important process has evolved. Ciliates
are among the earliest branching eukaryotes; their NMD mechanism is poorly
understood and may be primordial. We demonstrate that highly conserved Upf
proteins (Upf1a, Upf2 and Upf3) are involved in the NMD pathway of the ciliate,
Tetrahymena thermophila. We further show that a novel protozoa-specific nuclease,
Smg6L, is responsible for destroying many NMD-targeted transcripts. Transcriptome
wide identification and characterization of NMD-targeted transcripts in
vegetative Tetrahymena cells showed that many have exon-exon junctions downstream
of the termination codon. However, Tetrahymena may lack a functional exon
junction complex (EJC), and the Tetrahymena ortholog of an EJC core component,
Mago nashi (Mag1), is dispensable for NMD. Therefore, NMD is EJC independent in
this early branching eukaryote.
PMID- 28402569
TI - In Reply: Occipitocervical fixation: A single surgeon's experience with 120
patients.
PMID- 28402568
TI - How real-life health messages engage our brains: Shared processing of effective
anti-alcohol videos.
AB - Health communication via mass media is an important strategy when targeting risky
drinking, but many questions remain about how health messages are processed and
how they unfold their effects within receivers. Here we examine how the brains of
young adults-a key target group for alcohol prevention-'tune in' to real-life
health prevention messages about risky alcohol use. In a first study, a large
sample of authentic public service announcements (PSAs) targeting the risks of
alcohol was characterized using established measures of message effectiveness. In
the main study, we used inter-subject correlation analysis of fMRI data to
examine brain responses to more and less effective PSAs in a sample of young
adults. We find that more effective messages command more similar responses
within widespread brain regions, including the dorsomedial prefrontal cortex,
insulae and precuneus. In previous research, these regions have been related to
processing narratives, emotional stimuli, self-relevance and attention towards
salient stimuli. The present study thus suggests that more effective health
prevention messages have greater 'neural reach', i.e. they engage the brains of
audience members' more widely. This work outlines a promising strategy for
assessing the effects of health communication at a neural level.
PMID- 28402570
TI - Prescription Opioid Access Patterns and Factors Associated with Increasing Number
of Prescribers, Pharmacies, and Dispensings: An Observational Study Using
Pharmaceutical Claims.
AB - Objective: To examine associations between patient factors and increasing opioid
access measured by three metrics: number of unique prescribers, pharmacies, and
dispensings in 12 months. Methods: We used pharmaceutical claims for a random 10%
sample of Australians age 18 years or older initiating or reinitiating strong
opioid treatment (>=90 days of no strong opioid dispensing) between July 2010 and
December 2012. We report the distribution of opioid access by metric. We used
three separate zero-truncated negative binomial regressions to explore
associations. We censored individuals 365 days after index date or at death,
whichever occurred first. Results: Approximately 69,088 persons initiated or
reinitiated strong opioid treatment; they were predominantly female (59.7%) with
a median age of 71 years (interquartile range [IQR] = 58-81). Over one year,
persons visited a median of two prescribers (IQR = 1-3), visited one dispensing
pharmacy (IQR = 1-2), and had four opioid dispensings (IQR = 2-10). Three percent
of people were in the top decile of opioid access distribution for all three
metrics (four or more prescribers, three or more dispensing pharmacies, and 20 or
more dispensings). Increasing opioid access was strongly associated with male
sex, history of pain treatment (3 to 12 months prior to index date), malignancy
treatment, or treatment for three or more other medical conditions. Conclusions:
Delineating legitimate from extramedical opioid use based on pharmaceutical
claims is imprecise. We demonstrated that "high" levels of access, defined in
previous research, may reflect routine care for complex patients. Pharmaceutical
claims have utility in examining population norms of prescription drug use and
access patterns, and flagging persons at the extreme end of access, for at least
one measure, who may warrant further investigation.
PMID- 28402572
TI - Acute mesenteric venous thrombosis.
PMID- 28402571
TI - Neural correlates of emotion acceptance vs worry or suppression in generalized
anxiety disorder.
AB - Recent emotion dysregulation models of generalized anxiety disorder (GAD) propose
chronic worry in GAD functions as a maladaptive attempt to regulate anxiety
related to uncertain or unpredictable outcomes. Emotion acceptance is an adaptive
emotion regulation strategy increasingly incorporated into newer cognitive
behavioral therapy (CBT) approaches to GAD to counter chronic worry. The current
study explores the mechanisms of emotion acceptance as an alternate emotion
regulation strategy to worry or emotion suppression using functional magnetic
resonance imaging. Twenty-one female participants diagnosed with GAD followed
counterbalanced instructions to regulate responses to personally relevant worry
statements by engaging in either emotion acceptance, worry or emotion
suppression. Emotion acceptance resulted in lower ratings of distress than worry
and was associated with increased dorsal anterior cingulate cortex (dACC)
activation and increased ventrolateral prefrontal cortex (VLPFC)-amygdala
functional connectivity. In contrast, worry showed significantly greater distress
ratings than acceptance or suppression and was associated with increased
precuneus, VLPFC, amygdala and hippocampal activation. Suppression did not
significantly differ from acceptance in distress ratings or amygdala recruitment,
but resulted in significantly greater insula and VLPFC activation and decreased
VLPFC-amygdala functional connectivity. Emotion acceptance closely aligned with
activation and connectivity patterns reported in studies of contextual extinction
learning and mindful awareness.
PMID- 28402573
TI - Humor drawings evoked temporal and spectral EEG processes.
AB - The study aimed to explore the humor processing elicited through the manipulation
of artistic drawings. Using the Comprehension-Elaboration Theory of humor as the
main research background, the experiment manipulated the head portraits of
celebrities based on the independent variables of facial deformation
(large/small) and addition of affective features (positive/negative). A 64
channel electroencephalography was recorded in 30 participants while viewing the
incongruous drawings of celebrities. The electroencephalography temporal and
spectral responses were measured during the three stages of humor which included
incongruity detection, incongruity comprehension and elaboration of humor.
Analysis of event-related potentials indicated that for humorous vs non-humorous
drawings, facial deformation and the addition of affective features significantly
affected the degree of humor elicited, specifically: large > small deformation;
negative > positive affective features. The N170, N270, N400, N600-800 and N900
1200 components showed significant differences, particularly in the right
prefrontal and frontal regions. Analysis of event-related spectral perturbation
showed significant differences in the theta band evoked in the anterior cingulate
cortex, parietal region and posterior cingulate cortex; and in the alpha and beta
bands in the motor areas. These regions are involved in emotional processing,
memory retrieval, and laughter and feelings of amusement induced by elaboration
of the situation.
PMID- 28402576
TI - Finding the Right Balance.
AB - Since the 1980s, concerns about resident fatigue have caused lawmakers and
medical policymakers to pull back on resident duty hours. In 2003 and again in
2011, the Accreditation Council for Graduate Medical Education (ACGME) shortened
resident hours. In March, ACGME modified those hours again. The latest rule
change has reignited a long-running debate among physicians.
PMID- 28402574
TI - Hard to look on the bright side: neural correlates of impaired emotion regulation
in depressed youth.
AB - The cognitive regulation of emotion is impaired in major depressive disorder and
has been linked to an imbalance of pre-frontal-subcortical brain activity.
Despite suggestions that this relationship represents a neurodevelopmental marker
of depression, few studies have examined the neural correlates of emotion
regulation in depressed youth. We combined a 'cognitive reappraisal' paradigm
with functional magnetic resonance imaging to study the neural correlates of
emotional regulation in a large sample of non-medicated depressed adolescents and
young adults (n = 53) and healthy controls (n = 64). As compared with healthy
controls, young people with depression were less able to reduce negative affect
during reappraisal, which corresponded to blunted modulation of amygdala
activity. While in healthy individuals amygdala activation was modulated by age,
no such relationship was observed in depressed individuals. Heightened activation
of the ventromedial pre-frontal cortex (vmPFC) and reduced activation of the
dorsal midline cortex was also found for the depressed group. Overall, these
findings suggest that brain systems that support cognitive reappraisal are
functionally altered in youth depression. We argue that excessive engagement of
the vmPFC in particular, may be central to understanding how the process of
putting a 'positive spin' on negative emotional material may be altered in
depressed youth.
PMID- 28402575
TI - From the Cover: ImpairedProliferation and Differentiation of the Conducting
Airway Epithelium Associated With Bronchiolitis Obliterans After Sulfur Mustard
Inhalation Injury in Rats.
AB - : Sulfur mustard (SM) is a chemical warfare agent that causes chronic airway
remodeling. This study's objective was to assess for changes to the bronchiolar
epithelium after SM exposure to explain its contribution to chronic airway
remodeling. Materials and methods: Adult male rats were exposed to a sublethal
dose of SM inhalation (1.0-1.2 mg/kg) for 50 min. Histological sections of the
bronchiolar epithelium were analyzed for changes using hematoxylin and eosin,
trichrome, and immunofluorescent staining for acetylated tubulin (AT) and club
cell secretory protein (CCSP). CCSP in bronchoalveolar lavage fluid was assessed
using western blot. A bromodeoxyuridine (BRDU) assay was used to assess for
epithelial proliferation, and real-time PCR measured changes in Notch mRNA
expression. Results: SM caused significant proximal bronchiolar epithelial injury
with epithelial denudation, loss of acetylated tubulin and CCSP staining, and
reduced bronchoalveolar lavage fluid CCSP levels. bromodeoxyuridine (BRDU) +
staining of proximal bronchiolar epithelial cells was not increased, but staining
was increased in the distal bronchiolar epithelium. One month after injury, the
proximal bronchiolar epithelium was not fully repaired. Significant collagen
deposition surrounded proximal bronchioles with luminal obstruction, consistent
with bronchiolitis obliterans. These changes corresponded with a downregulation
of Notch1, Notch3, and Hes1 mRNA expressions. Conclusions: This study
demonstrates that SM exposure resulted in severe proximal airway epithelial
injury, persistent morphological changes, impaired epithelial proliferation and,
ultimately, bronchiolitis obliterans. These changes occurred at the same time
that the Notch signaling genes were downregulated. Thus, the lung epithelium and
the Notch signaling pathway may be worthy targets for the prevention of chronic
airway remodeling after SM inhalation injury.
PMID- 28402577
TI - A Second Shot at HPV.
AB - HPV vaccination rates remain stubbornly low, and some studies show physician
hesitancy about promoting the vaccine is the single biggest problem. TMA's HPV
Work Group plans to coordinate with like-minded state and national organizations
and agencies to come up with an action plan to improve HPV vaccination rates.
PMID- 28402578
TI - Relation of Mental Health to Alcohol and Substance Use Among Texas College
Students.
AB - We examined the effect of mental health problems and difficulties on alcohol,
tobacco, and other drug (ATOD) use among college students by using the 2013 Texas
College Survey of Substance Use (n=11,216), which includes the K6 screening scale
for severe mental illness (SMI). Students' K6 scores were used to classify them
into 3 groups: those likely to have SMI (9% with scores >= 13), those with some
mental health problems (36%), and those without mental health issues (55% with
scores <= 4). Questions regarding ATOD use were analyzed using these 3 groups.
Alcohol use was not significantly associated with K6 scores, although problematic
alcohol behaviors as measured by the CAGE test were. Higher cigarette use was
significantly associated with higher K6 scores. Finally, both higher marijuana
and higher drug use (across 9 other individual drugs) were significantly
associated with higher K6 scores. Although higher K6 scores were associated with
higher rates of drug use, most students with high K6 scores did not use drugs.
However, given the higher level of risk, drug and alcohol interventions should be
made available for those students who receive mental health counseling.
PMID- 28402579
TI - Glitch in the Switch.
AB - Migrating patient records from one electronic health record system to another can
be a nightmare. A La Porte pediatrician's experience provides a cautionary tale
for all physicians.
PMID- 28402580
TI - Change Around the Block?
AB - Proponents of a block grant or per-capita cap trumpet them as vehicles for the
federal government to give the states a capped amount of funding for Medicaid
that legislatures would effectively distribute how they see fit. Questions abound
as to what capped Medicaid funding would look like, and what effect it would have
on the current Medicaid-eligible population, covered services, and physician
payments.
PMID- 28402581
TI - Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed
or refractory chronic lymphocytic leukemia: Results from the N1087 alliance
study.
AB - Akt is a downstream target of B cell receptor signaling and is a central
regulator of CLL cell survival. We aim to investigate the safety and efficacy of
the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in
relapsed and/or refractory CLL in a phase I/II study. A standard phase I design
was used with cohorts of three plus three patients to determine the maximum
tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single
agent MK-2206 (weekly dosed) was administered one-week in advance before BR on
cycle 1 and subsequently was given with BR at the same time for cycle 2-6. Phase
II employed the MTD of MK-2206 with BR to evaluate safety and efficacy of this
study combination. Thirteen relapsed/refractory CLL were treated for maximal 6
cycle of therapy. The maximum tolerated dose of MK-2206 was 90 mg by mouth once
weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile
neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%).
Overall response rate was 92% with a median progression free survival and
treatment free survival of 16 and 24 months, respectively. Five patients (38%)
achieved complete remission or complete remission with incomplete count recovery,
two of whom were MRD negative. The efficacy and tolerability of this combination
indicates that Akt inhibition combined with chemoimmunotherapy is a promising
novel treatment combination in CLL and deserves further prospective clinical
trial.
PMID- 28402582
TI - Mechanical and structural characterization of whey protein
concentrate/montmorillonite/lycopene films.
AB - BACKGROUND: The production/characterization of nanocomposites based on whey
protein concentrate (WPC) and montmorillonite (MMT) with lycopene as functional
substance is presented and their potential use as alternative biomaterials in
foodstuff applications is discussed. A full factorial design with varying levels
of MMT (0 and 20 g kg-1 ) and lycopene (0, 60 and 120 g kg-1 ) was used. The
mechanical properties (tensile and puncture tests), thermal stability, Fourier
transform infrared vibrational spectra and film morphology of the resulting
materials were evaluated. RESULTS: Lycopene and MMT nanoparticles could be
successfully included in WPC films using the casting/evaporation method. The
films were flexible and homogeneous and a uniform dispersion of the components
was achieved. CONCLUSION: Inclusion of 20 g kg-1 of MMT in the polymeric matrix
improved both mechanical and thermal properties. Lycopene at the tested
concentrations, besides its red coloring ability, did not promote any detectable
interference in the structural or physical properties. These findings are
important in devising applications and open a new perspective on the use of these
materials in bioactive packaging processing. (c) 2017 Society of Chemical
Industry.
PMID- 28402583
TI - The potential indirect effects among plants via shared hummingbird pollinators
are structured by phenotypic similarity.
AB - Plant species within communities may overlap in pollinators' use and influence
visitation patterns of shared pollinators, potentially engaging in indirect
interactions (e.g., facilitation or competition). While several studies have
explored the mechanisms regulating insect-pollination networks, there is a lack
of studies on bird-pollination systems, particularly in species-rich tropical
areas. Here, we evaluated if phenotypic similarity, resource availability (floral
abundance), evolutionary relatedness and flowering phenology affect the potential
for indirect effects via shared pollinators in hummingbird-pollinated plant
species within four communities in the Brazilian Atlantic forest. Among the
evaluated factors, phenotypic similarity (corolla length and anther height) was
the most important variable, while resource availability (floral abundance) had a
secondary importance. On the other hand, evolutionary relatedness and flowering
phenology were less important, which altogether highlights the relevance of
convergent evolution and that the contribution of a plant to the diet of the
pollinators of another plant is independent of the level of temporal overlap in
flowering in this tropical system. Interestingly, our findings contrast with
results from multiple insect-pollinated plant communities, mostly from temperate
regions, in which floral abundance was the most important driver, followed by
evolutionary relatedness and phenotypic similarity. We propose that these
contrasting results are due to high level of specialization inherent to tropical
hummingbird-pollination systems. Moreover, our results demonstrated that factors
defining linkage rules of plant-hummingbird networks also determinate plant-plant
potential indirect effects. Future studies are needed to test if these findings
can be generalized to other highly specialized systems. Overall, our results have
important implications for the understanding of ecological processes due resource
sharing in mutualistic systems.
PMID- 28402584
TI - Pregnancy Complications and Women's Long-Term Health: Challenges for Research and
Care.
PMID- 28402585
TI - On the arguments between Dr Shinichi Watanabe and Drs Tsunemi and Hiruma
concerning the efficacy of the Dermatophyte Test Strip.
PMID- 28402586
TI - Shifts in community size structure drive temperature invariance of secondary
production in a stream-warming experiment.
AB - A central question at the interface of food-web and climate change research is
how secondary production, or the formation of heterotroph biomass over time, will
respond to rising temperatures. The metabolic theory of ecology (MTE)
hypothesizes the temperature-invariance of secondary production, driven by
matched and opposed forces that reduce biomass of heterotrophs while increasing
their biomass turnover rate (production : biomass, or P:B) with warming. To test
this prediction at the whole community level, we used a geothermal heat exchanger
to experimentally warm a stream in southwest Iceland by 3.8 degrees C for two
years. We quantified invertebrate community biomass, production, and P : B in the
experimental stream and a reference stream for one year prior to warming and two
years during warming. As predicted, warming had a neutral effect on community
production, but this result was not driven by opposing effects on community
biomass and P:B. Instead, warming had a positive effect on both the biomass and
production of larger-bodied, slower-growing taxa (e.g., larval black flies,
dipteran predators, snails) and a negative effect on small-bodied taxa with
relatively high growth rates (e.g., ostracods, larval chironomids). We attribute
these divergent responses to differences in thermal preference between small- vs.
large-bodied taxa. Although metabolic demand vs. resource supply must ultimately
constrain community production, our results highlight the potential for
idiosyncratic community responses to warming, driven by variation in thermal
preference and body size within regional species pools.
PMID- 28402588
TI - The Reactivity of Benzyl Lithium Species is Regulated by Intermediate Structures.
AB - The reaction of benzyl lithiums is an important aspect in organic and
organometallic synthesis. Reported herein are detailed insights into the
reactivity of benzyl lithiums as regulated by intermediate structures. By
discussing the carbometalation of allylamines and the reaction of the formed
benzyl-lithium compounds with electrophiles, the influence of the metal as well
as the solvent on the electronic structure of the intermediate is described. This
molecular structure strongly influences the reactivity of these intermediates. By
choosing the appropriate reaction conditions, the regioselectivity of reactions
with electrophiles can be regulated. With trimethylchlorosilane in n-pentane a
selective reaction at the para-position takes place. In contrast, selective
reaction at the benzylic position, with trimethylchlorostannane in
tetrahydrofuran (THF) as a solvent, is accomplished.
PMID- 28402587
TI - Methotraxate-Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit
Atherosclerosis Progression in ApoE-/- Mice.
AB - Atherosclerosis is an inflammatory disorder characterized by the progressive
thickening of blood vessel walls eventually resulting in acute vascular
syndromes. Here, intravenously injectable hybrid nanoconstructs are synthesized
for tempering immune cell inflammation locally and systemically. Lipid and
polymer chains are nanoprecipitated to form 100 nm spherical polymeric
nanoconstructs (SPNs), loaded with methotrexate (MTX) and subsequently labeled
with Cu64 and fluorescent probes for combined nuclear/optical imaging. Upon
engulfment into macrophages, MTX SPNs intracellularly release their anti
inflammatory cargo significantly lowering the production of proinflammatory
cytokine (interleukin 6 and tumor necrosis factor alpha) already at 0.06 mg mL-1
of MTX. In ApoE-/- mice, fed with high-fat diet up to 17 weeks, nuclear and
optical imaging demonstrates specific accumulation of SPNs within lipid-rich
plaques along the arterial tree. Histological analyses confirm SPN uptake into
macrophages residing within atherosclerotic plaques. A 4-week treatment with
biweekly administration of MTX SPNs is sufficient to reduce the plaque burden in
ApoE-/- mice by 50%, kept on high-fat diet for 10 weeks. Systemic delivery of MTX
to macrophages via multifunctional, hybrid nanoconstructs constitutes an
effective strategy to inhibit atherosclerosis progression and induce,
potentially, the resorption of vascular lesions.
PMID- 28402589
TI - Carbonate clumped isotope analyses with the long-integration dual-inlet (LIDI)
workflow: scratching at the lower sample weight boundaries.
AB - RATIONALE: Clumped isotope analyses (Delta47 ) of carbonates by dual inlet (DI)
mass spectrometry require long integration times to reach the necessary high
precision due to the low abundance of the rare isotopologue 13 C18 O16 O.
Traditional DI protocols reach this only with large amounts of sample and/or a
large number of replicates as a large portion of the analyte gas is wasted. We
tested an improved analytical workflow that significantly reduces the sample
sizes and total analysis time per sample while preserving precision and accuracy.
METHODS: We implemented the LIDI (long-integration dual-inlet) protocol to
measure carbonates in micro-volume mode using a Kiel IV carbonate device coupled
to a Thermo Scientific 253 Plus isotope ratio mass spectrometer without the new
1013 ohm amplifier technology. The LIDI protocol includes a single measurement of
the sample gas (600 s integration) followed by a single measurement of the
working gas (WG) with the same integration time. RESULTS: The Delta47
measurements of four calcite standards over a period of 5 weeks demonstrate
excellent long-term stability with a standard deviation of +/-0.021 to +/-0.025
0/00 for the final values of the individual aliquots. The Delta47 analyses of a
coral, four foraminifera and a calcite precipitated in the laboratory demonstrate
that 14 replicates of 90 to 120 MUg are sufficient to achieve an external
precision of +/-0.007 0/00 (1SE) or of +/-0.013 0/00 at the 95% confidence level.
CONCLUSIONS: This study demonstrates that by using a Kiel IV-253 Plus system with
LIDI it is possible to achieve the same analytical precision as conventional DI
measurements with at least a factor of 40 less sample material. With the new 1013
ohm resistor technology there is the potential to reduce the required sample
material even more. This opens new avenues of research in paleoceanography,
paleoclimatology, low-temperature diagenesis and other currently sample size
limited applications. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28402590
TI - Non-Thermal Plasma Activation of Gold-Based Catalysts for Low-Temperature Water
Gas Shift Catalysis.
AB - Non-thermal plasma activation has been used to enable low-temperature water-gas
shift over a Au/CeZrO4 catalyst. The activity obtained was comparable with that
attained by heating the catalyst to 180 degrees C providing an opportunity for
the hydrogen production to be obtained under conditions where the thermodynamic
limitations are minimal. Using in situ diffuse reflectance infrared Fourier
transform spectroscopy (DRIFTS), structural changes associated with the gold
nanoparticles in the catalyst have been observed which are not found under
thermal activation indicating a weakening of the Au-CO bond and a change in the
mechanism of deactivation.
PMID- 28402591
TI - An Ion-Responsive Pincer-Crown Ether Catalyst System for Rapid and Switchable
Olefin Isomerization.
AB - Rapid, selective, and highly controllable iridium-catalyzed allylbenzene
isomerization is described, enabled by tunable hemilability based on alkali metal
cation binding with a macrocyclic "pincer-crown ether" ligand. An inactive
chloride-ligated complex can be activated by halide abstraction with sodium
salts, with the resulting catalyst [kappa5 -(15c5 NCOPiPr )Ir(H)]+ exhibiting
modest activity. Addition of Li+ provides a further boost in activity, with up to
1000-fold rate enhancement. Ethers and chloride salts dampen or turn off
reactivity, leading to three distinct catalyst states with activity spanning
several orders of magnitude. Mechanistic studies suggest that the large rate
enhancement and high degree of tunability stem from control over substrate
binding.
PMID- 28402592
TI - Photo- and Electronically Switchable Spin-Crossover Iron(II) Metal-Organic
Frameworks Based on a Tetrathiafulvalene Ligand.
AB - A major challenge is the development of multifunctional metal-organic frameworks
(MOFs), wherein magnetic and electronic functionality can be controlled
simultaneously. Herein, we rationally construct two 3D MOFs by introducing the
redox active ligand tetra(4-pyridyl)tetrathiafulvalene (TTF(py)4 ) and spin
crossover FeII centers. The materials exhibit redox activity, in addition to
thermally and photo-induced spin crossover (SCO). A crystal-to-crystal
transformation induced by I2 doping has also been observed and the resulting
intercalated structure determined. The conductivity could be significantly
enhanced (up to 3 orders of magnitude) by modulating the electronic state of the
framework via oxidative doping; SCO behavior was also modified and the photo
magnetic behavior was switched off. This work provides a new strategy to tune the
spin state and conductivity of framework materials through guest-induced redox
state switching.
PMID- 28402593
TI - A new method for the production of sterile colonies of Lucilia sericata.
AB - Maggot debridement therapy (MDT) refers to the use of blowfly larvae to clean or
debride an infected wound. Most commonly, larvae of Lucilia sericata (Meigen)
(Diptera: Calliphoridae) are used, and are sterilized prior to use to ensure no
further bacterial infections are introduced during treatment. Current methods
sterilize eggs from laboratory-reared blowfly colonies, after which sterile early
second instar maggots can be provided to hospitals for use in treatment. Maggots
not required for treatment are used for colony regeneration, in which sterility
is not maintained. The ability to maintain sterility beyond this would allow
further research into fly-bacteria interactions and the effects of different
bacteria on the blowfly lifecycle. This study aimed to produce a colony of
sterile adults, using current egg sterilization practice, but maintaining
sterility through to pupation and emergence. The production of a sterile colony
allows further research into the impact of bacteria on fly development and
survival. Eggs were placed on a sterile food source within autoclaved plant
tissue culture containers to allow growth under sterile conditions. Nutrient agar
plating of sterilized and non-sterilized eggs, larvae and adults (post
emergence), as well as the pupation medium and feed source in nutrient broth
confirmed the aerobic sterility of all samples involved. The lifecycle of L.
sericata was successfully completed through pupation to emergence with no effects
on lifespan or oviposition by the newly emerged, sterile adult colony.
PMID- 28402594
TI - Tumor Microenvironment-Triggered Aggregation of Antiphagocytosis 99m Tc-Labeled
Fe3 O4 Nanoprobes for Enhanced Tumor Imaging In Vivo.
AB - A tumor microenvironment responsive nanoprobe is developed for enhanced tumor
imaging through in situ crosslinking of the Fe3 O4 nanoparticles modified with a
responsive peptide sequence in which a tumor-specific Arg-Gly-Asp peptide for
tumor targeting and a self-peptide as a "mark of self" are linked through a
disulfide bond. Positioning the self-peptide at the outmost layer is aimed at
delaying the clearance of the nanoparticles from the bloodstream. After the self
peptide is cleaved by glutathione within tumor microenvironment, the exposed
thiol groups react with the remaining maleimide moieties from adjacent particles
to crosslink the particles in situ. Both in vitro and in vivo experiments
demonstrate that the aggregation substantially improves the magnetic resonance
imaging (MRI) contrast enhancement performance of Fe3 O4 particles. By labeling
the responsive particle probe with 99m Tc, single-photon emission computed
tomography is enabled not only for verifying the enhanced imaging capacity of the
crosslinked Fe3 O4 particles, but also for achieving sensitive dual modality
imaging of tumors in vivo. The novelty of the current probe lies in the
combination of tumor microenvironment-triggered aggregation of Fe3 O4
nanoparticles for boosting the T2 MRI effect, with antiphagocytosis surface
coating, active targeting, and dual-modality imaging, which is never reported
before.
PMID- 28402595
TI - Recent Advances in Atomic Metal Doping of Carbon-based Nanomaterials for Energy
Conversion.
AB - Nanostructured metal-contained catalysts are one of the most widely used types of
catalysts applied to facilitate some of sluggish electrochemical reactions.
However, the high activity of these catalysts cannot be sustained over a variety
of pH ranges. In an effort to develop highly active and stable metal-contained
catalysts, various approaches have been pursued with an emphasis on metal
particle size reduction and doping on carbon-based supports. These techniques
enhances the metal-support interactions, originating from the chemical bonding
effect between the metal dopants and carbon support and the associated interface,
as well as the charge transfer between the atomic metal species and carbon
framework. This provides an opportunity to tune the well-defined metal active
centers and optimize their activity, selectivity and stability of this type of
(electro)catalyst. Herein, recent advances in synthesis strategies,
characterization and catalytic performance of single atom metal dopants on carbon
based nanomaterials are highlighted with attempts to understand the electronic
structure and spatial arrangement of individual atoms as well as their
interaction with the supports. Applications of these new materials in a wide
range of potential electrocatalytic processes in renewable energy conversion
systems are also discussed with emphasis on future directions in this active
field of research.
PMID- 28402596
TI - From Two- to Three-Dimensional Structures of a Supertetrahedral Boran Using
Density Functional Calculations.
AB - With help of the DFT calculations and imposing of periodic boundary conditions
the geometrical and electronic structures were investigated of two- and three
dimensional boron systems designed on the basis of graphane and diamond lattices
in which carbons were replaced with boron tetrahedrons. The consequent studies of
two- and three-layer systems resulted in the construction of a three-dimensional
supertetrahedral borane crystal structure. The two-dimensional supertetrahedral
borane structures with less than seven layers are dynamically unstable. At the
same time the three-dimensional superborane systems were found to be dynamically
stable. Lack of the forbidden electronic zone for the studied boron systems
testifies that these structures can behave as good conductors. The low density of
the supertetrahedral borane crystal structures (0.9 g cm-3 ) is close to that of
water, which offers the perspective for their application as aerospace and cosmic
materials.
PMID- 28402598
TI - Development of Simple QSPR Models for the Prediction of the Heat of Decomposition
of Organic Peroxides.
AB - Quantitative structure-property relationships represent alternative method to
experiments to access the estimation of physico-chemical properties of chemicals
for screening purpose at R&D level but also to gather missing data in regulatory
context. In particular, such predictions were encouraged by the REACH regulation
for the collection of data, provided that they are developed respecting the
rigorous principles of validation proposed by OECD. In this context, a series of
organic peroxides, unstable chemicals which can easily decompose and may lead to
explosion, were investigated to develop simple QSPR models that can be used in a
regulatory framework. Only constitutional and topological descriptors were
employed to achieve QSPR models predicting the heat of decomposition, which could
be used without any time consuming preliminary structure calculations at quantum
chemical level. To validate the models, the original experimental dataset was
divided into a training and a validation set according to two methods of
partitioning, one based on the property value and the other based on the
structure of the molecules by the mean of PCA. Four QSPR models were developed
upon the type of descriptors and the methods of partitioning. The 2 models
issuing from the PCA based method were highlighted as they presented good
predictive power and they are easier to apply than our previous quantum chemical
based model, since they do not need any preliminary calculations.
PMID- 28402597
TI - Gene-gene interaction of single nucleotide polymorphisms in 16p13.3 may
contribute to the risk of non-syndromic cleft lip with or without cleft palate in
Chinese case-parent trios.
AB - Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth
defect with a complex and heterogeneous etiology. A recent genome-wide
association study (GWAS) among Chinese populations has identified a new region at
16p13.3 as being associated with NSCL/P, which requires further replication.
Here, we attempted to replicate and further clarify the genetic association
between this region and NSCL/P, as well as testing for potential gene-gene (G *
G) and gene-environment (G * E) interactions. We conducted transmission
disequilibrium tests on 69 single nucleotide polymorphisms (SNPs) mapping to
16p13.3 among 806 Chinese case-parent trios ascertained through an international
consortium where a GWAS of oral clefts was conducted. G * G, as well as G * E
interactions involving maternal environmental tobacco smoke (ETS) and
multivitamin supplementation, were explored using conditional logistic regression
model. We applied Cordell's method as implemented in the R package TRIO to test
for possible interactions. While no SNPs showed evidence of linkage and
association with NSCL/P after Bonferroni correction, we found signals of G * G
interactions between SNPs in 16p13.3. Nine pairs of SNP-SNP interactions attained
significance after Bonferroni correction, among which the most significant
interaction was found between rs2072346 (ADCY9) and rs11646137 (intergenic
region, P = 7.2 * 10-5 ). Linkage disequilibrium (LD) analysis revealed only low
level of LD between these SNPs. This study failed to confirm the significant
association between SNPs within 16p13.3 and the risk of NSCL/P, but underlined
the importance of taking into account potential G * G interactions for the
genetic association analysis of NSCL/P.
PMID- 28402599
TI - Obtention and characterization of dried gels prepared with whey proteins, honey
and hydrocolloids mixture.
AB - BACKGROUND: Large amounts of honey and liquid whey derived from the dairy
industry are produced in Argentina. Honey is exported in bulk and whey is
transformed into whey protein concentrates and isolates. The objective of this
work was to investigate the effect of pH, composition and storage time on the
properties of dried gels with honey, whey proteins and hydrocolloids. RESULTS:
Color properties varied according to pH and composition. The fracture stress of
dried gels prepared with corn starch was higher than that of gels prepared with
guar gum in all conditions assayed. Young's modulus was higher at pH 7 for both
compositions and increased with storage time. Rubbery characteristics were found
in dried gels with guar gum, while both corn starch and guar gum made the
microstructure rougher. Multivariate analysis showed that samples could be
grouped by pH. Panelists preferred pH 7 products over acidic ones, and no
significant differences in sensory properties were found using either corn starch
or guar gum in the formulation. CONCLUSION: The results demonstrated that it is
possible to generate a new product, which may open new applications for honey and
whey in food formulations. (c) 2017 Society of Chemical Industry.
PMID- 28402600
TI - Magneto-Adaptive Surfactants Showing Anti-Curie Behavior and Tunable Surface
Tension as Porogens for Mesoporous Particles with 12-Fold Symmetry.
AB - Gaining external control over self-organization is of vital importance for future
smart materials. Surfactants are extremely valuable for the synthesis of diverse
nanomaterials. Their self-assembly is dictated by microphase separation, the
hydrophobic effect, and head-group repulsion. It is desirable to supplement
surfactants with an added mode of long-range and directional interaction.
Magnetic forces are ideal, as they are not shielded in water. We report on
surfactants with heads containing tightly bound transition-metal centers. The
magnetic moment of the head was varied systematically while keeping shape and
charge constant. Changes in the magnetic moment of the head led to notable
differences in surface tension, aggregate size, and contact angle, which could
also be altered by an external magnetic field. The most astonishing result was
that the use of magnetic surfactants as structure-directing agents enabled the
formation of porous solids with 12-fold rotational symmetry.
PMID- 28402601
TI - Complementary Lock-and-Key Ligand Binding of a Triplet Transmitter to a
Nanocrystal Photosensitizer.
AB - Owing to the difficulty in comprehensively characterizing nanocrystal (NC)
surfaces, clear guidance for ligand design is lacking. In this work, a series of
bidentate bis(pyridine) anthracene isomers (2,3-PyAn, 3,3-PyAn, 2,2-PyAn) that
differ in their binding geometries were designed to find the best complementary
fit to the NC surface. The efficiency of triplet energy transfer (TET) from the
CdSe NC donor to a diphenylanthracene (DPA) acceptor mediated by these isomers
was used as a proxy for the efficacy of orbital overlap and therefore ligand
binding. 2,3-PyAn, with an intramolecular N-N distance of 8.2 A, provided the
best match to the surface of CdSe NCs. When serving as a transmitter for photon
upconversion, 2,3-PyAn yielded the highest upconversion quantum yield (QY) of
12.1+/-1.3 %, followed by 3,3-PyAn and 2,2-PyAn. The TET quantum efficiencies
determined by ultrafast transient absorption measurements showed the same trend.
PMID- 28402602
TI - A Plastic-Crystal Electrolyte Interphase for All-Solid-State Sodium Batteries.
AB - The development of all-solid-state rechargeable batteries is plagued by a large
interfacial resistance between a solid cathode and a solid electrolyte that
increases with each charge-discharge cycle. The introduction of a plastic-crystal
electrolyte interphase between a solid electrolyte and solid cathode particles
reduces the interfacial resistance, increases the cycle life, and allows a high
rate performance. Comparison of solid-state sodium cells with 1) solid
electrolyte Na3 Zr2 (Si2 PO4 ) particles versus 2) plastic-crystal electrolyte in
the cathode composites shows that the former suffers from a huge irreversible
capacity loss on cycling whereas the latter exhibits a dramatically improved
electrochemical performance with retention of capacity for over 100 cycles and
cycling at 5 C rate. The application of a plastic-crystal electrolyte interphase
between a solid electrolyte and a solid cathode may be extended to other all
solid-state battery cells.
PMID- 28402603
TI - An electrospray ionization mass spectrometry study of azidoacetic acid/transition
metal complexes.
AB - RATIONALE: The complexation behavior of transition metals with organic azides by
electrospray ionization (ESI) tandem mass spectrometry (MS/MS) is not completely
understood. In this study, fragmentation patterns of complex ions having
azidoacetic acid coordinated to Ni/Co/Fe were elucidated. The role of transition
metals in the mediation of ligand rearrangements in gas phase is experimentally
supported. METHODS: The complexation of some transition metals, nickel, cobalt
and iron, by azidoacetic acid was studied by means of ESI and MS/MS.
Fragmentation patterns were discerned via consecutive MS/MS experiments on an ion
trap mass spectrometer and confirmed by high-resolution (HR) Fourier transform
ion cyclotron resonance MS. Density functional theory (DFT) calculations were
used to characterize the major ions observed in MS. RESULTS: Only singly
positively charged complex ions were detected presenting various stoichiometries.
MS/MS and theoretical calculations allowed us to confirm assignments and
coordination sites. Structural evidence suggested that the azidoacetic acid can
behave as monodentate and/or bidentate and coordination through the oxygen and
nitrogen atoms are both possible. Experimental evidence strongly points to a role
of Ni/Co/Fe, in oxidative state (I), in mediating C-C bond activation in the gas
phase. CONCLUSIONS: MS/MS and HRMS experiments were able to elucidate azidoacetic
acid complexation with Ni/Co/Fe and several gas-phase processes involving metal
reduction and rearrangements. The definition of the coordination pattern dictated
by the competition between the nitrogen and the oxygen atoms is also dependent on
the metal centre in a very dynamic process. Copyright (c) 2017 John Wiley & Sons,
Ltd.
PMID- 28402604
TI - Isolated Single Iron Atoms Anchored on N-Doped Porous Carbon as an Efficient
Electrocatalyst for the Oxygen Reduction Reaction.
AB - The development of low-cost, efficient, and stable electrocatalysts for the
oxygen reduction reaction (ORR) is desirable but remains a great challenge.
Herein, we made a highly reactive and stable isolated single-atom Fe/N-doped
porous carbon (ISA Fe/CN) catalyst with Fe loading up to 2.16 wt %. The catalyst
showed excellent ORR performance with a half-wave potential (E1/2 ) of 0.900 V,
which outperformed commercial Pt/C and most non-precious-metal catalysts reported
to date. Besides exceptionally high kinetic current density (Jk ) of 37.83 mV cm
2 at 0.85 V, it also had a good methanol tolerance and outstanding stability.
Experiments demonstrated that maintaining the Fe as isolated atoms and
incorporating nitrogen was essential to deliver the high performance. First
principle calculations further attributed the high reactivity to the high
efficiency of the single Fe atoms in transporting electrons to the adsorbed OH
species.
PMID- 28402605
TI - Biotin-thiamine responsive basal ganglia disease: Identification of a pyruvate
peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of
prevalence based on allele frequencies from aggregated next-generation sequencing
data.
AB - Biotin-thiamine responsive basal ganglia disease is an inborn error of metabolism
caused by mutations in SLC19A3, encoding a transporter of thiamine across the
plasma membrane. We report a novel mutation identified in the homozygous state in
a patient with typical brain MRI changes. In addition, this patient had markedly
elevated CSF pyruvate, a low lactate-to-pyruvate molar ratio, and an abnormal
pyruvate peak at 2.4 ppm on brain magnetic resonance spectroscopy. Using
aggregated exome sequencing data, we calculate the carrier frequency of mutations
in SLC19A3 as 1 in 232 individuals in the general population, for an estimated
prevalence of the disease of approximately 1 in 215,000 individuals. The disease
is thus more frequent than previously recognized, and the presence of a pyruvate
peak on spectroscopy could serve as an important diagnostic clue.
PMID- 28402607
TI - Frustrated Lewis Pair Chemistry: Searching for New Reactions.
AB - Frustrated Lewis pair chemistry has taken a steep development in the recent
years. It offers possibilities of developing new variants of known reactions and
of finding new chemical transformations. This is demonstrated and described by
the recently developed FLP-formylborane chemistry, which has led to the formation
of the unique (eta2 -formylborane)FLP adducts and opened a way of preparing a
genuine formylborane compound, which shows an interesting follow-up chemistry.
FLPs have helped finding phosphorus analogues of the enamine Stork reaction and
the Claisen reaction. These reactions lead to new organophosphorus compounds and
they make new phosphane/borane systems available. P/B FLPs add to a variety of
small main group element oxides. They undergo 1,2-addition reactions to CO2 , SO2
and other heterocumulenes and they feature unique 1,1-addition reactions to
carbon monoxide, to isonitriles and even to nitric oxide (NO), the latter
yielding examples of a new class of persistent nitroxide radicals, the FLPNO
nitroxyls. Eventually, some remarkable radical reactions of FLPs and related
compounds are briefly mentioned.
PMID- 28402608
TI - A Fast Algorithm to Compute Conical Pockets in Proteins. Application to the
Structural Characterization of gamma-Carbonic Anhydrases.
AB - Some major proteins families, such as carbonic anhydrases (CAs), have a conical
cavity at the active site. No algorithm was available to compute conical
cavities, so we needed to design one. The fast algorithm we designed let us show
on a set of 717 CAs extracted from the PDB database that gamma-CAs are
characterized by active site cavity cone angles significantly larger than those
of alpha-CAs and beta-CAs: the generatrix-axis angles are greater than 60 degrees
for the gamma-CAs while they are smaller than 50 degrees for the other CAs.
Free binaries of the CONICA software implementing the algorithm are available
through a software repository at
http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.html.
PMID- 28402606
TI - Timing of paclitaxel treatment in pre-operative or post-operative does not affect
survival in breast cancer patients.
AB - BACKGROUND: Two epirubicin and paclitaxel-based neoadjuvant chemotherapy regimens
were compared in breast cancer patients. METHODS: We enrolled 309 breast cancer
patients who received two types of regimens: cyclophosphamide + epirubicin dose
dense neoadjuvant chemotherapy followed by sequential postoperative paclitaxel
single-drug medication, and paclitaxel + epirubicin standard neoadjuvant
chemotherapy followed by two cycles of the same chemotherapy after surgery. The
primary endpoint was a pathological complete response (pCR) and the secondary
endpoints were disease-free and overall survival. RESULTS: The median follow-up
time was 65 months. The overall pCRs for pathological efficacy and efficacy of
primary lesions were 14.4% and 29.3%, respectively (P < 0.001). The pCR of the
paclitaxel + epirubicin group was significantly higher than in the
cyclophosphamide + epirubicin group (17.3% vs. 9.2%; P = 0.0345), but the five
year disease-free survival rates in both groups were not significantly different
(82.9% vs. 75.3%; P = 0.916). CONCLUSIONS: The results of our study indicated
that the timing of paclitaxel therapy, either preoperative or postoperative, does
not affect survival times in breast cancer patients.
PMID- 28402609
TI - Evans and Blandy, Dentists and Men of Mystery in Paris and London in the 19th
Century.
AB - This article was originally presented as the annual Orland lecture at the 65th
American Academy of the History of Dentistry meeting in London, UK.
PMID- 28402610
TI - Historical Perspectives IV: Creative Management of Fractured Teeth.
AB - Various contemporary efforts have been advocated to strengthen root-treated teeth
to prevent fracture; or to manage teeth that exhibit fractures. These efforts
have favored the use of newer, adhesive materials, incorporating horizontally
transfixed fiberglass posts to stabilize the fractured segments. Results have
been encouraging, as teeth tested have exhibited fracture resistance similar to
that found with onlays. However, this concept is not new and in spite of not
having the advantages of adhesive dental materials, including the fiberglass
posts, efforts that were made close to 100 years ago to stabilize and retain
fractured teeth were reasonably successful.
PMID- 28402611
TI - Categorizing Children Dental Patients, Circa 1927.
PMID- 28402612
TI - Origins of Dental Education and Training in the USA and UK.
AB - This paper is based on a talk given at a dinner hosted by the American Academy of
the History of Dentistry. It examines some early efforts towards dental education
and training on both sides of the Atlantic. For British attendees I dealt (and
thus in this paper) especially with the roles of Horace Hayden and Chapin Harris
in developing formal dental training in the United States of America. For
Americans, I contrast those developments with how dentistry arose in the United
Kingdom. Major figures such as John Tomes were involved, with close links to
surgery. The first qualifications in the USA were degrees whereas in the UK they
were Royal College of Surgeons diplomas, degrees only being awarded from 1906.
PMID- 28402614
TI - From the Archives: Vol. 6, Nos. 1 & 2.
PMID- 28402613
TI - Tushmaker's Tooth Puller: The Beginning of Dentistry's Technological Revolution?
PMID- 28402621
TI - Specific Imaging of Intracellular Lipid Droplets Using a Benzothiadiazole
Derivative with Solvatochromic Properties.
AB - Altered lipid metabolism and extensive lipid storage in cells have been
associated with various medical disorders, including cancer. The development of
fluorescent probes that specifically accumulate in lipid deposits is therefore of
great interest in order to study pathological processes that are linked to
dysregulated lipogenesis. In the present study, we present a small fluorescent
benzothiadiazole dye that specifically stains lipid droplets in living and
fixated cells. The photophysical characterization of the probe revealed strong
solvatochromic behavior, large Stokes shifts, and high fluorescent quantum yields
in hydrophobic solvents. In addition, the fluorophore exhibits a nontoxic profile
and a high signal-to-noise ratio in cells (i.e., lipid droplets vs cytosol),
which make it an excellent candidate for studying lipid biology using confocal
fluorescent microscopy.
PMID- 28402622
TI - Broken Symmetry Induced Strong Nonlinear Optical Effects in Spiral WS2
Nanosheets.
AB - Transition metal dichalcogenides (TMDs) have provided a fundamental stage to
study light-matter interactions and optical applications at the atomic scale due
to their ultrathin thickness and their appropriate band gap in the visible
region. Here, we report the strong nonlinear optical effects, including second
harmonic generation (SHG) and third-harmonic generation (THG) in spiral WS2
structures. SHG intensity quadratically increases with layer numbers, other than
diminishing the oscillation of 2H stacking TMDs. The contrary SHG behavior is
attributed to the broken symmetry from twisted screw structures, revealed by
aberration-corrected transmission electronic microscope observation. Furthermore,
the twist angle of the screw structure (5 degrees) was obtained by high
resolution transmission microscope measurements and confirmed by polarization
tests of SHG output. Moreover, we roughly estimate the effective second-order
nonlinear susceptibility. The discovery and understanding of the accumulation of
nonlinear susceptibility of spiral structures with increasing thickness will
extend the nonlinear applications of TMDs.
PMID- 28402623
TI - Growth Termination and Multiple Nucleation of Single-Wall Carbon Nanotubes
Evidenced by in Situ Transmission Electron Microscopy.
AB - In order to controllably grow single-wall carbon nanotubes (SWCNTs), a better
understanding of the growth processes and how they are influenced by external
parameters such as catalyst and gaseous environment is required. Here, we present
direct evidence of growth termination of individual SWCNTs and successive growth
of additional SWCNTs on Co catalyst particles supported on MgO by means of
environmental transmission electron microscopy. Such in situ observations reveal
the plethora of solid carbon formations at the local scale while it is happening
and thereby elucidate the multitude of configurations resulting from identical
external synthesis conditions, which should be considered in the quest for
controlled SWCNT growth. Using CO and a mixture of CO and H2 as carbon sources,
we show that the growth of SWCNTs terminates with a reduced tube-catalyst
adhesion strength. Two main reasons for the cessation are proposed: insufficient
active carbon species and a certain amount of stress exerted at the tube-catalyst
interface. Interestingly, it was observed that catalyst particles stayed active
in terms of nucleating additional solid carbon structures after growth
termination of the first SWCNT. These observations elucidate the importance of an
in-depth understanding of the role of catalysts and carbon sources in the
continued growth of SWCNTs. Furthermore, it serves as a guide for further control
of carbon nanostructure synthesis via catalyst engineering and synthesis
optimization.
PMID- 28402624
TI - Near-Infrared Photochemoimmunotherapy by Photoactivatable Bifunctional Antibody
Drug Conjugates Targeting Human Epidermal Growth Factor Receptor 2 Positive
Cancer.
AB - Near-infrared photoimmunotherapy (NIR-PIT) is a new class of molecular targeted
cancer therapy based on antibody-photoabsorber conjugates and NIR light
irradiation. Recent studies have shown effective tumor control, including that of
human epidermal growth factor receptor 2 (HER2)-positive cancer, by selective
molecular targeting with NIR-PIT. However, the depth of NIR light penetration
limits its use. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate
consisting of the monoclonal antibody trastuzumab linked to the cytotoxic agent
maytansinoid DM1. Here, we developed bifunctional antibody-drug-photoabsorber
conjugates, T-DM1-IR700, that can work as both NIR-PIT and chemoimmunotherapy
agents. We evaluated the feasibility of T-DM1-IR700-mediated NIR light
irradiation by comparing the in vitro and in vivo cytotoxic efficacy of
trastuzumab-IR700 (T-IR700)-mediated NIR light irradiation in HER2-expressing
cells. T-IR700 and T-DM1-IR700 showed almost identical binding to HER2 in vitro
and in vivo. Owing to the presence of internalized DM1 in the target cells, NIR
PIT using T-DM1-IR700 tended to induce greater cytotoxicity than that of NIR-PIT
using T-IR700 in vitro. In vivo NIR-PIT using T-DM1-IR700 did not show a superior
antitumor effect to NIR-PIT using T-IR700 in subcutaneous small-tumor models,
which could receive sufficient NIR light. In contrast, NIR-PIT using T-DM1-IR700
tended to reduce the tumor volume and showed significant prolonged survival
compared to NIR-PIT using T-IR700 in large-tumor models that could not receive
sufficient NIR light. We successfully developed a T-DM1-IR700 conjugate that has
a similar immunoreactivity to the parental antibody with increased cytotoxicity
due to DM1 and potential as a new NIR-PIT agent for targeting tumors that are
large and inaccessible to sufficient NIR light irradiation to activate the
photoabsorber IR700.
PMID- 28402625
TI - Interplay of Internal Structure and Interfaces on the Emitting Properties of
Hybrid ZnO Hierarchical Particles.
AB - The design of hybrid organic/inorganic nanostructures with controlled assembly
drives the development of materials with new or improved properties and superior
performances. In this paper, the surface and internal structure of hybrid ZnO
poly-N-vinylpyrrolidone (ZnO/PVP) mesocrystals are investigated in detail and
correlated with their emitting properties. A photoluminescence study at room
temperature reveals that the as-synthesized particles show a remarkable
ultraviolet (UV) emission, whereas an emission from defects in the visible region
is not observed. On the other hand, a visible emission is achieved upon
calcination of the hybrid ZnO/PVP particles in air, and its intensity is found to
increase with the calcination temperature and, in some cases, to overwhelm the UV
emission. A molecular description is proposed for the absence of a visible
emission from defects in the as-synthesized ZnO/PVP mesocrystals on the basis of
Fourier transform infrared (FTIR) and solid-state 13C NMR (SSNMR) spectroscopy.
An in-depth electron microscopy study sheds light on the internal organization of
mesocrystals and reveals the formation of nanoreactors, that is, particles with
enclosed porosity, upon thermal treatment.
PMID- 28402626
TI - A Combination of Boron Nitride Nanotubes and Cellulose Nanofibers for the
Preparation of a Nanocomposite with High Thermal Conductivity.
AB - With the current development of modern electronics toward miniaturization, high
degree integration and multifunctionalization, considerable heat is accumulated,
which results in the thermal failure or even explosion of modern electronics. The
thermal conductivity of materials has thus attracted much attention in modern
electronics. Although polymer composites with enhanced thermal conductivity are
expected to address this issue, achieving higher thermal conductivity (above 10 W
m-1 K-1) at filler loadings below 50.0 wt % remains challenging. Here, we report
a nanocomposite consisting of boron nitride nanotubes and cellulose nanofibers
that exhibits high thermal conductivity (21.39 W m-1 K-1) at 25.0 wt % boron
nitride nanotubes. Such high thermal conductivity is attributed to the high
intrinsic thermal conductivity of boron nitride nanotubes and cellulose
nanofibers, the one-dimensional structure of boron nitride nanotubes, and the
reduced interfacial thermal resistance due to the strong interaction between the
boron nitride nanotubes and cellulose nanofibers. Using the as-prepared
nanocomposite as a flexible printed circuit board, we demonstrate its potential
usefulness in electronic device-cooling applications. This thermally conductive
nanocomposite has promising applications in thermal interface materials, printed
circuit boards or organic substrates in electronics and could supplement
conventional polymer-based materials.
PMID- 28402627
TI - Strategy for the Quantitation of a Protein Conjugate via Hybrid Immunocapture
Liquid Chromatography with Sequential HRMS and SRM-Based LC-MS/MS Analyses.
AB - With the development of modern instrumentation and technologies, mass
spectrometry based assays have played an important role in protein bioanalysis.
We have developed a novel strategy by combining the "bottom-up" and "top-down"
approaches using both high-resolution (HRMS) and selected reaction monitoring
(SRM) based mass spectrometric detection to quantify a positron emission
tomography (PET) detection tracer for an oncology marker. Monkey plasma samples
were processed by immunocapture purification, followed by liquid chromatography
(LC) with HRMS full scan analysis. Summed multiple charge states and multiple
isotopes per charge state of the analyte were used during quantitation for
optimized sensitivity. After the HRMS analysis, the remaining samples were
digested by trypsin, followed by SRM detection. The HRMS approach provided the
solution to a unique problem related to stability of the protein conjugate by
quantifying the intact protein. The SRM method only measured a signature peptide
generated from enzymatic digestion, but had a lower quantitation limit to meet
the sensitivity requirement to assess the pharmacokinetics in a toxicology study.
Both methods demonstrated good sensitivity, accuracy, precision and robustness,
and the results revealed that there was no significant difference between the
data sets obtained from both methods, indicating no in vivo or ex vivo
degradation occurred in the incurred samples after dosing. This workflow not only
provided the quantitative results for pharmacokinetic evaluation, but also
revealed valuable in vivo stability information on the intact protein level.
PMID- 28402628
TI - Influences of Normalization Method on Biomarker Discovery in Gas Chromatography
Mass Spectrometry-Based Untargeted Metabolomics: What Should Be Considered?
AB - Data reduction techniques in gas chromatography-mass spectrometry-based
untargeted metabolomics has made the following workflow of data analysis more
lucid. However, the normalization process still perplexes researchers, and its
effects are always ignored. In order to reveal the influences of normalization
method, five representative normalization methods (mass spectrometry total useful
signal, median, probabilistic quotient normalization, remove unwanted variation
random, and systematic ratio normalization) were compared in three real data sets
with different types. First, data reduction techniques were used to refine the
original data. Then, quality control samples and relative log abundance plots
were utilized to evaluate the unwanted variations and the efficiencies of
normalization process. Furthermore, the potential biomarkers which were screened
out by the Mann-Whitney U test, receiver operating characteristic curve analysis,
random forest, and feature selection algorithm Boruta in different normalized
data sets were compared. The results indicated the determination of the
normalization method was difficult because the commonly accepted rules were easy
to fulfill but different normalization methods had unforeseen influences on both
the kind and number of potential biomarkers. Lastly, an integrated strategy for
normalization method selection was recommended.
PMID- 28402629
TI - Binding of Thioflavin-T to Amyloid Fibrils Leads to Fluorescence Self-Quenching
and Fibril Compaction.
AB - Thioflavin-T binds to and detects amyloid fibrils via fluorescence enhancement.
Using a combination of linear dichroism and fluorescence spectroscopies, we
report that the relation between the emission intensity and binding of thioflavin
T to insulin fibrils is nonlinear and discuss this in relation to its use in
kinetic assays. We demonstrate, from fluorescence lifetime recordings, that the
nonlinearity is due to thioflavin-T being sensitive to self-quenching. In
addition, thioflavin-T can induce fibril compaction but not alter fibril
structure. Our work underscores the photophysical complexity of thioflavin-T and
the necessity of calibrating the linear range of its emission response for
quantitative in vitro studies.
PMID- 28402631
TI - Remote Mutations Induce Functional Changes in Active Site Residues of Human DNA
Polymerase beta.
AB - With the formidable growth in the volume of genetic information, it has become
essential to identify and characterize mutations in macromolecules not only to
predict contributions to disease processes but also to guide the design of
therapeutic strategies. While mutations of certain residues have a predictable
phenotype based on their chemical nature and known structural position, many
types of mutations evade prediction based on current information. Described in
this work are the crystal structures of two cancer variants located in the palm
domain of DNA polymerase beta (pol beta), S229L and G231D, whose biological
phenotype was not readily linked to a predictable structural implication.
Structural results demonstrate that the mutations elicit their effect through
subtle influences on secondary interactions with a residue neighboring the active
site. Residues 229 and 231 are 7.5 and 12.5 A, respectively, from the nearest
active site residue, with a beta-strand between them. A residue on this
intervening strand, M236, appears to transmit fine structural perturbations to
the catalytic metal-coordinating residue D256, affecting its conformational
stability.
PMID- 28402632
TI - AgPd Nanoparticles Deposited on WO2.72 Nanorods as an Efficient Catalyst for One
Pot Conversion of Nitrophenol/Nitroacetophenone into Benzoxazole/Quinazoline.
AB - We report a seed-mediated growth of 2.3 nm AgPd nanoparticles (NPs) in the
presence of 40 * 5 nm WO2.72 nanorods (NRs) for the synthesis of AgPd/WO2.72
composites. The strong interactions between AgPd NPs and WO2.72 NRs make the
composites, especially the Ag48Pd52/WO2.72, catalytically active for
dehydrogenation of formic acid (TOF = 1718 h-1 and Ea = 31 kJ/mol) and one-pot
reactions of formic acid, 2-nitrophenol, and aldehydes into benzoxazoles in near
quantitative yields under mild conditions. The catalysis can also be extended to
the one-pot reactions of ammonium formate, 2-nitroacetophenone, and aldehyde for
high yield syntheses of quinazolines. Our studies demonstrate a new catalyst
design to achieve a green chemistry approach to one-pot reactions for the
syntheses of benzoxazoles and quinazolines.
PMID- 28402630
TI - Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and
TAF1/TAF1L Bromodomains.
AB - Bromodomains (BD) are readers of lysine acetylation marks present in numerous
proteins associated with chromatin. Here we describe a dual inhibitor of the
bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding
protein-associated factors TAF1 and TAF1L. These proteins are found in large
chromatin complexes and play important roles in transcription regulation. The
substituted benzoisoquinolinedione series was identified by high-throughput
screening, and subsequent structure-activity relationship optimization allowed
generation of low nanomolar BRPF2 BD inhibitors with strong selectivity against
BRPF1 and BRPF3 BDs. In addition, a strong inhibition of TAF1/TAF1L BD2 was
measured for most derivatives. The best compound of the series was BAY-299, which
is a very potent, dual inhibitor with an IC50 of 67 nM for BRPF2 BD, 8 nM for
TAF1 BD2, and 106 nM for TAF1L BD2. Importantly, no activity was measured for
BRD4 BDs. Furthermore, cellular activity was evidenced using a BRPF2- or TAF1
histone H3.3 or H4 interaction assay.
PMID- 28402633
TI - Determination of the Absolute Configuration of Khellactone Esters from Peucedanum
japonicum Roots.
AB - Sixteen new angular dihydropyranocoumarins (1-16) and 24 known compounds were
isolated from the roots of Peucedanum japonicum Thunb. The absolute configuration
of diacylkhellactone was established by partial hydrolysis, the Mosher method,
and X-ray crystallography. In addition, ECD spectroscopy was used to assign the
absolute configurations of several of the angular dihydropyranocoumarins.
Enantiomers were detected by RP-HPLC using MTPA esters while acyl migration of
the substituents was observed in cis-monoacylkhellactones.
PMID- 28402634
TI - Synthesis and Biological Evaluation of Bile Acid Analogues Inhibitory to
Clostridium difficile Spore Germination.
AB - Standard antibiotic-based strategies for the treatment of Clostridium difficile
infections disrupt indigenous microbiota and commonly fail to eradicate bacterial
spores, two key factors that allow recurrence of infection. As an alternative
approach to controlling C. difficile infection, a series of bile acid derivatives
have been prepared that inhibit taurocholate-induced spore germination. These
analogues have been evaluated in a highly virulent NAP1 strain using optical
density and phase-contrast microscopy assays. Heterocycle substitutions at C24
were well-tolerated and several tetrazole-containing derivatives were highly
potent inhibitors in both assays, with complete inhibition of spore germination
observed at 10-25 MUM. To limit intestinal absorption, C7-sulfated analogues
designed to avoid active and passive transport pathways were prepared. One of
these derivatives, compound 21b, was found to be a potent inhibitor of C.
difficile spore germination and poorly permeable in a Caco-2 model of intestinal
epithelial absorption, suggesting that it is likely to be gut-restricted.
PMID- 28402636
TI - An Efficient Analytic Approach for Calculation of Multi-Dimensional Franck-Condon
Factors and Associated Photoelectron Spectra.
AB - The implementation, optimization, and performance of a generalized analytic
treatment of multidimensional Franck-Condon Factors (FCF) within the harmonic
oscillator approximation and associated photoelectron spectra (PES) for N
dimensional systems, including consideration of Eckart conditions in the
displacement minimization and Cartesian coordinate handedness for evaluation of
the Duschinsky Effect, is carried out in this work. A new efficient strategy for
algorithmic efficiency for high dimensional systems is introduced, and
demonstrated for 3-, 15-, and 30-dimensional systems. Determination of the
photoelectron spectra for H2O+ (B2B2), vinyl alcohol, and C6H6+ (X2E1g) validates
the capabilities with a high degree of accuracy with respect to experiment.
PMID- 28402635
TI - Hydrogenation and Hydrosilylation of Nitrous Oxide Homogeneously Catalyzed by a
Metal Complex.
AB - Due to its significant contribution to stratospheric ozone depletion and its
potent greenhouse effect, nitrous oxide has stimulated much research interest
regarding its reactivity modes and its transformations, which can lead to its
abatement. We report the homogeneously catalyzed reaction of nitrous oxide (N2O)
with H2. The reaction is catalyzed by a PNP pincer ruthenium complex, generating
efficiently only dinitrogen and water, under mild conditions, thus providing a
green, mild methodology for removal of nitrous oxide. The reaction proceeds
through a sequence of dihydrogen activation, "O"-atom transfer, and dehydration,
in which metal-ligand cooperation plays a central role. This approach was further
developed to catalytic O-transfer from N2O to Si-H bonds.
PMID- 28402637
TI - Conformational Changes of a Surface-Tethered Polymer during Radical Growth Probed
with Second-Harmonic Generation.
AB - The surface-induced polymerization of a chromophore-functionalized monomer was
probed in situ for the first time using a nonlinear optical technique, second
harmonic generation. During the first hours of the polymerization reaction,
dramatic changes in the tilt angle of the chromophore-functionalized side groups
were observed. Following evaluation of the nonlinear optical data with those
obtained from atomic force microscopy and ultraviolet-visible, we conclude that
second-harmonic generation efficiently probes the polymerization reaction and the
conformational changes of the surface-grafted polymer. With polymerization time,
the conformation of the surface-tethered polymer changes from a conformation with
the polymer backbone and its side groups flat on the surface, i.e., a "pancake"
conformation, to a conformation where the polymer backbone is stretched away
combined with tilted side groups or an enlarged tilt angle distribution, i.e., a
"brush-type" conformation.
PMID- 28402638
TI - General Approaches to Structurally Diverse Isocyanoditerpenes.
AB - Since their discovery in the 1970s, the striking architectures and the unusual
isonitrile functional groups of the isocyanoterpenes have attracted the interest
of many organic chemists. The more recent revelation of their potent in vitro
antiplasmodial activity sparked new endeavors to synthesize members of this
family of secondary metabolites. In this Synopsis, we discuss three distinct
strategies that each address multiple structurally different members of the
isocyanoterpenes, ending with some of our group's recent contributions in this
area.
PMID- 28402639
TI - A Simple Approach for Predicting the Spin State of Homoleptic Fe(II) Tris-diimine
Complexes.
AB - We propose a simple method for predicting the spin state of homoleptic complexes
of the Fe(II) d6 ion with chelating diimine ligands. The approach is based on the
analysis of a single metric parameter within a free (noncoordinated) ligand: the
interatomic separation between the N-donor metal-binding sites. An extensive
analysis of existing complexes allows the determination of critical N...N
distances that dictate the regions of stability for the high-spin and low-spin
complexes, as well as the intermediate range in which the magnetic bistability
(spin crossover) can be observed. The prediction has been tested on several
complexes that demonstrate the validity of our method.
PMID- 28402641
TI - Self-Assembled Morphologies of Linear and Miktoarm Star Triblock Copolymer
Monolayers.
AB - Monolayers of linear and miktoarm star ABC triblock copolymers with equal A and C
blocks were investigated using self-consistent field theory. Monolayers of ABC
triblock copolymers were formed between two parallel surfaces that were
attractive to the A and C blocks. The repulsive interaction parameter chiACN
between the A and C blocks was chosen to be weaker than the A/B and B/C
interactions, quantified by chiABN and chiBCN, respectively, such that the B
blocks were confined at the A/C interface, resulting in various B domains with
different geometries and arrangements. It was observed that two variables,
namely, the strength of the surface fields and the film thickness, were dominant
factors controlling the self-assembly of the B blocks into various morphologies.
For the linear triblock copolymers, the morphologies of the B domains included
disks, stripes (parallel cylinders), and hexagonal networks (inverse disks). For
the miktoarm star triblock copolymers, the competition between the tendency to
align the junction points along a straight line and the constraint on their
arrangement from the surface interactions led to richer ordered morphologies. As
a result of the packing of the junction points of the ABC miktoarm star
copolymers, a counterintuitive phase sequence from low-curvature phases to high
curvature phases with increasing length of B block was predicted. The study
indicates that the self-assembly of monolayers of ABC triblock copolymers
provides an interesting platform for engineering novel morphologies.
PMID- 28402642
TI - Pd-Boron-Catalyzed One Carbon Isomerization of Olefins: Water Assisted Process at
Room Temperature.
AB - A palladium-boronate/borane-system -catalyzed isomerization of olefins has been
uncovered. An efficient catalytic combination of [Pd(OAc)2]3-boronate-PCy3
enabled olefin isomerization at 80 degrees C has been investigated. Addition of
water to the reaction showed a remarkable improvement and the isomerization
occurred at ambient temperature. These catalytic systems function efficiently for
the isomerization of functionalized as well as unfunctionalized olefins. The
catalytic conditions demonstrate the involvement of both nonhydride and metal
hydride medium and can be switchable with water as an additive.
PMID- 28402643
TI - Coverage-Dependent Anchoring of 4,4'-Biphenyl Dicarboxylic Acid to CoO(111) Thin
Films.
AB - We investigated the adsorption behavior of 4,4'-biphenhyl dicarboxylic acid (BDA)
on well-ordered CoO(111) films grown on Ir(100) as a function of coverage and
temperature using time-resolved and temperature-programmed infrared reflection
absorption spectroscopy (TR-IRAS, TP-IRAS) in combination with density functional
theory (DFT) and scanning tunneling microscopy (STM) under ultrahigh vacuum (UHV)
conditions. To compare the binding behavior of BDA as a function of the oxide
film thickness, three different CoO(111) film thicknesses were explored: films of
about 20 bilayers (BLs) (approximately 5 nm), 2 BLs, and 1 BL. The two carboxylic
acid groups of BDA offer two potential anchoring points to the oxide surface. At
150 K, intact BDA adsorbs on 20 BL thick oxide films in planar geometry with the
phenyl rings aligned parallel to the surface. With decreasing oxide film
thickness, we observe an increasing tendency for deprotonation and the formation
of flat-lying BDA molecules anchored as dicarboxylates. After saturation of the
first monolayer, intact BDA multilayers grow with molecules aligned parallel to
the surface. The BDA multilayer desorbs at around 360 K. Completely different
growth behavior is observed if BDA is deposited above the multilayer desorption
temperature. Initially, doubly deprotonated dicarboxylates are formed by adopting
a flat-lying orientation. With increasing exposure, however, the adsorbate layer
transforms into upright standing monocarboxylates. A sharp OH stretching band
(3584 cm-1) and a blue-shifted CO stretching band (1759 cm-1) indicate weakly
interacting apical carboxylic acid groups at the vacuum interface. The anchored
monocarboxylate phase slowly desorbs in a temperature range of up to 470 K. At
higher temperature, a flat-lying doubly deprotonated BDA is formed, which desorbs
and decomposes in a temperature range of up to 600 K.
PMID- 28402640
TI - Mutagenic Replication of N2-Deoxyguanosine Benzo[a]pyrene Adducts by Escherichia
coli DNA Polymerase I and Sulfolobus solfataricus DNA Polymerase IV.
AB - Benzo[a]pyrene, a potent human carcinogen, is metabolized in vivo to a diol
epoxide that reacts with the N2-position of guanine to produce N2-BP-dG adducts.
These adducts are mutagenic causing G to T transversions. These adducts block
replicative polymerases but can be bypassed by the Y-family translesion synthesis
polymerases. The mechanisms by which mutagenic bypass occurs is not well-known.
We have evaluated base pairing structures using atomic substitution of the dNTP
with two stereoisomers, 2'-deoxy-N-[(7R,8S,9R,10S)-7,8,9,10-tetrahydro-7,8,9
trihydroxybenzo[a]pyren-10-yl]guanosine and 2'-deoxy-N-[(7S,8R,9S,10R)-7,8,9,10
tetrahydro-7,8,9-trihydroxybenzo[a]pyren-10-yl]guanosine. We have examined the
kinetics of incorporation of 1-deaza-dATP, 7-deaza-dATP, 2'-deoxyinosine
triphosphate, and 7-deaza-dGTP, analogues of dATP and dGTP in which single atoms
are changed. Changes in rate will occur if that atom provided a critical
interaction in the transition state of the reaction. We examined two polymerases,
Escherichia coli DNA polymerase I (Kf) and Sulfolobus solfataricus DNA polymerase
IV (Dpo4), as models of a high fidelity and TLS polymerase, respectively. We
found that with Kf, substitution of the nitrogens on the Watson-Crick face of the
dNTPs resulted in decreased rate of reactions. This result is consistent with a
Hoogsteen base pair in which the template N2-BP-dG flipped from the anti to syn
conformation. With Dpo4, while the substitution did not affect the rate of
reaction, the amplitude of the reaction decreased with all substitutions. This
result suggests that Dpo4 bypasses N2-BP-dG via Hoogsteen base pairs but that the
flipped nucleotide can be either the dNTP or the template.
PMID- 28402644
TI - Investigation of the Halogenate-Hydrogen Peroxide Reactions Using the Electron
Paramagnetic Resonance Spin Trapping Technique.
AB - The differences in the mechanism of the halogenate reactions with the same
oxidizing/reducing agent, such as H2O2 contribute to the better understanding of
versatile halogen chemistry. The reaction between iodate, bromate, and chlorate
with hydrogen peroxide in acidic medium at 60 degrees C is investigated by using
the electron paramagnetic resonance (EPR) spin trapping technique. Essential
differences in the chemistry of iodate, bromate, and chlorate in their reactions
with hydrogen peroxide have been evidenced by finding different radicals as
governing intermediates. The reaction between KIO3 and H2O2 is supposed to be the
source of IO2* radicals. The KBrO3 and H2O2 reaction did not produce any EPR
signal, whereas the KClO3-H2O2 system was found to be a source of HO* radical.
Moreover, KClO3 dissolved in sulfuric acid without hydrogen peroxide produced HO*
radical as well. The minimal-core models explaining the origin of obtained EPR
signals are proposed. Current findings suggested the inclusion of IO2* and HOO*
radicals, and ClO2* and HO* radicals in the particular kinetic models of iodate
hydrogen peroxide and chlorate-hydrogen peroxide systems, as well as possible
exclusion of BrO2* radical from the kinetic scheme of the bromate-hydrogen
peroxide system. Obtained results may pave the way for understanding more
complex, nonlinear reactions of these halogen-containing species.
PMID- 28402645
TI - Copper-Catalyzed Regioselective Synthesis of Multisubstituted Furans by Coupling
between Ketones and Aromatic Olefins.
AB - A regioselective synthesis of multisubstituted furan derivatives has been
developed via Cu(II)-catalyzed intermolecular annulation of aryl ketones with a
wide range of aromatic olefins under ambient air in good yields. This protocol is
applicable to both cyclic and acyclic aryl ketones.
PMID- 28402646
TI - Coulomb-Enhanced Radiative Recombination of Biexcitons in Single Giant-Shell
CdSe/CdS Core/Shell Nanocrystals.
AB - Giant-shell CdSe/CdS core/shell nanocrystals have attracted much attention due to
their unique quasi-type-II band alignment, where a large valence band offset
confines holes strongly to the core but electrons are delocalized due to a small
conduction band offset. Here, we report the observation of the relative
enhancement in the radiative recombination rate of a biexciton compared to that
of an exciton in giant-shell CdSe/CdS nanocrystals. We found a clear correlation
between the shell thickness of the CdSe/CdS nanocrystals and the ratio between
the radiative recombination rates of the biexciton and exciton. Our finding can
be explained by a picture in which the biexciton emission efficiency is enhanced
through electron localization around the core due to the strong Coulomb potential
of the two holes confined in the core.
PMID- 28402647
TI - Recyclable Dirhodium(II) Catalyst Rh2(esp)2 for the Allylic Oxidation of Delta5
Steroids.
AB - The chelating dirhodium(II) catalyst Rh2(esp)2 was shown to efficiently catalyze
the allylic oxidation of Delta5-steroids using T-HYDRO (70% tert-butyl
hydroperoxide in water) as oxidant. Reaction yields were affected by the
coordination ability of the solvent. The noncoordinating solvent n-heptane was
determined to be an optimal solvent. At gram scale, the product, Delta5-en-7-one
steroid, precipitated from the reaction mixture. The Rh2(esp)2 complex did not
undergo catalytic degradation and was recycled using Merrifield-pyridine resin
for further allylic oxidation cycles. The results of ultraviolet/visible spectral
analysis suggested that the Rh2(II,II) species, rather than the Rh2(II,III)
species, was in the catalyst resting state during the reaction, which helps to
explain the high durability of the catalyst.
PMID- 28402648
TI - Copper-Catalyzed Cascade Transformation of Homopropargyl Azides into
Trifluoromethylated Nitriles via C-C Cleavage.
AB - A cascade reaction of homopropargyl azides in the presence of a Cu catalyst was
achieved, affording 3-(trifluoromethyl)but-3-enenitriles with good yields and
excellent regioselectivity. This reaction appears to be the first direct
conversion of homopropargyl azides into trifluoromethylated nitriles. Mechanistic
studies indicate that the transformation proceeds by addition of a CF3 radical to
the alkyne, C-C cleavage by 1,4-aryl radical migration, and nitrile formation.
This protocol provides a novel strategy for transforming azides into nitriles via
C-C cleavage derived from radical migration.
PMID- 28402649
TI - Synthesis of Chainlike ZSM-5 Zeolites: Determination of Synthesis Parameters,
Mechanism of Chainlike Morphology Formation, and Their Performance in Selective
Adsorption of Xylene Isomers.
AB - Chainlike zeolites are advantageous to various applications as a catalyst or an
adsorbent with specific selectivity; however, it is often very difficult to get
desired morphology due to the complexity of zeolite synthesis process. In this
work, appropriate parameters for the synthesis of perfect chainlike ZSM-5
zeolites were well determined, which illustrates that the chain length can be
controlled by the composition of synthesis mixture, the amount of residual
alcohol in the synthesis system, and the crystallization time. Moreover, the
mechanism of chainlike crystal growth was investigated by analyzing the surface
species during the synthesis process, with the help of density functional theory
(DFT) calculation. The results indicate that the formation of disk crystals with
proper dimension and flat surface having abundant hydroxyl groups is crucial to
the growth of chainlike ZSM-5 crystals; the condensation of Si-OH groups on the
(010) facet is energetically more favorable than that on other facets, leading to
the growth of MFI crystals along the b-orientation. Through finely tuning the
multifarious synthesis parameters, chainlike ZSM-5 zeolites with controllable
length in b-orientation are obtained without using any other extra organic
additives except the necessary template agent such as tetrapropylammonium
hydroxide (TPAOH). Owing to the increased tortuosity of pore channels in the
chainlike ZSM-5, the difference between p-xylene and o/m-xylenes in their
adsorption behavior and diffusivity is greatly enhanced. These results help to
clarify the formation mechanism of zeolites with chainlike morphology and then
bring forward an effective approach to get zeolite materials with specific
properties in adsorption and catalysis.
PMID- 28402650
TI - Comprehensive Analytical Approach toward Glycomic Characterization and Profiling
in Urinary Exosomes.
AB - Exosomes are extracellular nanosized vesicles with lipid bilayers encapsulating
nucleic acids and proteins, both with and without glycosylation. While exosomal
nucleic acids and proteins have previously been explored to identify cancer
biomarkers with some promising results, little information has been available
concerning their glycoconjugate content. Exosomes were isolated from normal urine
samples through multistep differential centrifugation. The isolated exosomes have
an average size of 146 nm and a spherical shape, as determined by dynamic light
scattering and transmission electron microscopy, respectively. N-Glycans were
enzymatically released from the isolated vesicles. After being reduced and
permethylated, N-glycans were measured by MALDI mass spectrometry.
Paucimannosidic, high-mannose, and complex type glycans were identified and their
relative abundances were determined. Some detailed structures of these glycans
were revealed through liquid chromatography/tandem mass spectrometry (LC/MS-MS).
The reduced N-glycans, without being permethylated, were also separated and
analyzed by LC/MS-MS, and their structures were further detailed through isomeric
separation on porous graphitized carbon (PGC) packed in long capillaries. Using
microfractionation before LC/MS-MS, minor multiantennary N-glycans were
preconcentrated as based on hydrophobicity or charge. Preconcentration of the
reduced and permethylated glycans on a C18 cartridge revealed numerous large
glycans, whereas fractionation of the reduced N-glycans by ion-exchange
cartridges facilitated detection of sulfated glycans. After removing N-glycans
from the original sample aliquot, O-glycans were chemically released from urinary
exosomes and profiled, revealing some unusual structures.
PMID- 28402651
TI - DNA Bipedal Motor Achieves a Large Number of Steps Due to Operation Using
Microfluidics-Based Interface.
AB - Realization of bioinspired molecular machines that can perform many and diverse
operations in response to external chemical commands is a major goal in
nanotechnology, but current molecular machines respond to only a few sequential
commands. Lack of effective methods for introduction and removal of command
compounds and low efficiencies of the reactions involved are major reasons for
the limited performance. We introduce here a user interface based on a
microfluidics device and single-molecule fluorescence spectroscopy that allows
efficient introduction and removal of chemical commands and enables detailed
study of the reaction mechanisms involved in the operation of synthetic molecular
machines. The microfluidics provided 64 consecutive DNA strand commands to a DNA
based motor system immobilized inside the microfluidics, driving a bipedal walker
to perform 32 steps on a DNA origami track. The microfluidics enabled removal of
redundant strands, resulting in a 6-fold increase in processivity relative to an
identical motor operated without strand removal and significantly more operations
than previously reported for user-controlled DNA nanomachines. In the motor
operated without strand removal, redundant strands interfere with motor operation
and reduce its performance. The microfluidics also enabled computer control of
motor direction and speed. Furthermore, analysis of the reaction kinetics and
motor performance in the absence of redundant strands, made possible by the
microfluidics, enabled accurate modeling of the walker processivity. This enabled
identification of dynamic boundaries and provided an explanation, based on the
"trap state" mechanism, for why the motor did not perform an even larger number
of steps. This understanding is very important for the development of future
motors with significantly improved performance. Our universal interface enables
two-way communication between user and molecular machine and, relying on concepts
similar to that of solid-phase synthesis, removes limitations on the number of
external stimuli. This interface, therefore, is an important step toward
realization of reliable, processive, reproducible, and useful externally
controlled DNA nanomachines.
PMID- 28402652
TI - Regio- and Diastereoselective Cross-Dehydrogenative Coupling of
Tetrahydropyridines with 1,3-Dicarbonyl Compounds.
AB - A regio- and diastereoselective cross-dehydrogenative coupling of N-carbamoyl
tetrahydropyridines with a variety of 1,3-dicarbonyl compounds is described. The
method exhibits good functional group tolerance, diastereoselectively generating
cis-2,6- or cis-2,4-substituted tetrahydropyridines by using different types of
1,3-dicarbonyls. Moreover, a two-step sequence involving diastereoselective cross
dehydrogenative coupling followed by epimerization was also developed, allowing
facile access to trans-2,6-substituted tetrahydropyridines as single isomers.
Applications in natural product synthesis and divergent analogue preparation were
further demonstrated.
PMID- 28402653
TI - Host Cell Protein Profiling by Targeted and Untargeted Analysis of Data
Independent Acquisition Mass Spectrometry Data with Parallel Reaction Monitoring
Verification.
AB - Host cell proteins (HCPs) are process-related impurities of biopharmaceuticals
that remain at trace levels despite multiple stages of downstream purification.
Currently, there is interest in implementing LC-MS in biopharmaceutical HCP
profiling alongside conventional ELISA, because individual species can be
identified and quantitated. Conventional data dependent LC-MS is hampered by the
low concentration of HCP-derived peptides, which are 5-6 orders of magnitude less
abundant than the biopharmaceutical-derived peptides. In this paper, we present a
novel data independent acquisition (DIA)-MS workflow to identify HCP peptides
using automatically combined targeted and untargeted data processing, followed by
verification and quantitation using parallel reaction monitoring (PRM).
Untargeted data processing with DIA-Umpire provided a means of identifying HCPs
not represented in the assay library used for targeted, peptide-centric, data
analysis. An IgG1 monoclonal antibody (mAb) purified by Protein A column elution,
cation exchange chromatography, and ultrafiltration was analyzed using the
workflow with 1D-LC. Five protein standards added at 0.5 to 100 ppm
concentrations were detected in the background of the purified mAb, demonstrating
sensitivity to low ppm levels. A calibration curve was constructed on the basis
of the summed peak areas of the three highest intensity fragment ions from the
highest intensity peptide of each protein standard. Sixteen HCPs were identified
and quantitated on the basis of the calibration curve over the range of low ppm
to over 100 ppm in the purified mAb sample. The developed approach achieves rapid
HCP profiling using 1D-LC and specific identification exploiting the high mass
accuracy and resolution of the mass spectrometer.
PMID- 28402654
TI - Control of Ligand pKa Values Tunes the Electrocatalytic Dihydrogen Evolution
Mechanism in a Redox-Active Aluminum(III) Complex.
AB - Redox-active ligands bring electron- and proton-transfer reactions to main-group
coordination chemistry. In this Forum Article, we demonstrate how ligand pKa
values can be used in the design of a reaction mechanism for a ligand-based
electron- and proton-transfer pathway, where the ligand retains a negative charge
and enables dihydrogen evolution. A bis(pyrazolyl)pyridine ligand, iPrPz2P,
reacts with 2 equiv of AlCl3 to afford [(iPrPz2P)AlCl2(THF)][AlCl4] (1). A
reaction involving two-electron reduction and single-ligand protonation of 1
affords [(iPrHPz2P-)AlCl2] (2), where each of the electron- and proton-transfer
events is ligand-centered. Protonation of 2 would formally close a catalytic
cycle for dihydrogen production. At -1.26 V versus SCE, in a 0.3 M
Bu4NPF6/tetrahydrofuran solution with salicylic acid or (HNEt3)+ as the source of
H+, 1 produced dihydrogen electrocatalytically, according to cyclic voltammetry
and controlled potential electrolysis experiments. The mechanism for the reaction
is most likely two electron-transfer steps followed by two chemical steps based
on the available reactivity information. A comparison of this work with our
previously reported aluminum complexes of the phenyl-substituted
bis(imino)pyridine system (PhI2P) reveals that the pKa values of the N-donor
atoms in iPrPz2P are lower, which facilitates reduction before ligand
protonation. In contrast, the PhI2P ligand complexes of aluminum are protonated
twice before reduction liberates dihydrogen.
PMID- 28402655
TI - Self-Assembly of Extended Head-to-Tail Triangular Pt3 Macrocycles into Nanotubes.
AB - New pyridylsalicylaldimine-based ligands with extended conjugation have been
synthesized. The reaction of these ligands with K2PtCl4 yielded triangular Pt3
macrocycles rather than the anticipated Pt4 macrocycles. The macrocycles have
been analyzed in solution by variable-temperature and variable-concentration 1H
NMR, NOESY, and DOSY spectroscopy studies. These investigations show that the
macrocycles aggregate at room temperature in solution by an entropy-driven
process. In the solid state, matrix-assisted laser desorption/ionization time-of
flight mass spectrometry and transmission electron microscopy studies show that
the macrocycles aggregate into nanotubular structures. Triangular platinum
containing macrocycles with the expanded pyridylsalicylaldimine ligands are
promising for constructing nanotubes and discotic liquid crystals.
PMID- 28402656
TI - Comment on "Terrestrial Scavenging of Marine Mammals: Cross-Ecosystem Contaminant
Transfer and Potential Risks to Endangered California Condors (Gymnogyps
californianus)".
PMID- 28402657
TI - A Functional Zn(II) Metallacycle Formed from an N-Heterocyclic Carbene Precursor:
A Molecular Sensor for Selective Recognition of Fe3+ and IO4- Ions.
AB - We have reported the synthesis and structural characterization of a unique Zn(II)
metallacycle (1) and its utilization as a fluorescent probe for the shape
specific selective recognition (turn-off) of Fe3+ and IO4- ions. The relevant
Stern-Volmer graphs indicate that the recognitions of Fe3+ and IO4- ions are
examples of diphasic and monophasic quenchings, respectively. The title
metallacycle has been prepared by the reaction of a novel N-heterocyclic carbene
precursor, 1,3-bis(2,6-diisopropyl-4-(pyridin-4-yl)phenyl)-1H-imidazol-3-ium
chloride/bromide (L), and zinc(II) chloride salt. Notably, the ligand itself did
not show any type of recognition for any ions. DFT calculations were performed on
L and metallacycle 1 using the geometric parameters, obtained from their single
crystal X-ray diffraction data, to understand the electronic structures of the
ligand and macrocycle. The detection limit for the recognition of the Fe3+ ion
was determined to be 2.5 * 10-6 mol/L, and that for IO4- ion was found to be 6.3
* 10-5 mol/L.
PMID- 28402658
TI - Amplified Photon Upconversion by Photonic Shell of Cholesteric Liquid Crystals.
AB - As an effective platform to exploit triplet-triplet-annihilation-based photon
upconversion (TTA-UC), microcapsules composed of a fluidic UC core and photonic
shell are microfluidically prepared using a triple emulsion as the template. The
photonic shell consists of cholesteric liquid crystals (CLCs) with a periodic
helical structure, exhibiting a photonic band gap. Combined with planar anchoring
at the boundaries, the shell serves as a resonance cavity for TTA-UC emission and
enables spectral tuning of the UC under low-power-density excitation. The CLC
shell can be stabilized by introducing a polymerizable mesogen in the LC host.
Because of the microcapsule spherical symmetry, spontaneous emission of the
delayed fluorescence is omnidirectionally amplified at the edge of the stop band.
These results demonstrate the range of opportunities provided by TTA-UC systems
for the future design of low-threshold photonic devices.
PMID- 28402659
TI - Development of the ABEEMsigmapi Polarization Force Field for Base Pairs with
Amino Acid Residue Complexes.
AB - DNA damage caused by oxidized bases can lead to aging and cancer in living
beings. Luckily, a repair enzyme is able to repair the oxidized bases. The key
step is to accurately recognize the oxidized bases, which mainly rely on complex
hydrogen bond interactions. We have calibrated the charge parameters and
torsional parameters of the ABEEMsigmapi polarization force field (ABEEMsigmapi
PFF) to accurately describe the intermolecular and intramolecular interactions.
Taking the experiment and quantum chemical method as the benchmark, a series of
properties of base pair-amino acid residue systems, DNA and DNA-protein
interaction systems were calculated and compared with those of other force
fields. We have done a tremendous amount of tasks in testing, calibrations, and
analyses. The ABEEMsigmapi PFF not only explicitly gives the position and the
partial charge of lone-pair electrons but also introduces a function kHB to fit
special electrostatic interactions in hydrogen bond interaction regions.
Therefore, it can accurately simulate the polarization effect and charge transfer
of hydrogen bond interactions, especially for charged systems and sulfur
containing systems, such as the binding energy between amino acid and base pairs
(24-28 kcal/mol), which is induced by charge transfer. The RMSD of ABEEMsigmapi
PFF is 1.18 kcal/mol, whereas the RMSD of Amber OL15 is 8.21 kcal/mol. The
relative positions of the amino acid residue have significantly changed, and the
hydrogen bonds were broken when simulated by fixed charge force fields. In
addition, owing to refitting the reasonable torsional parameters, the geometric
structures optimized by ABEEMsigmapi PFF were well consistent with those of the
M06-2X/6-311++G** method, but the simulations by fixed force fields have a large
rotation of methyl and distortion of the plane of the base pair. After extensive
MD simulation with four test DNAs and a DNA-protein system, we conclude that
ABEEMsigmapi PFF shows better agreement when compared to experimental structures,
which illustrates the reliability of our model and the transferability of the
parameters.
PMID- 28402660
TI - Reply to Comment on "Terrestrial Scavenging of Marine Mammals: Cross-Ecosystem
Contaminant Transfer and Potential Risks to Endangered California Condors
(Gymnogyps californianus)".
PMID- 28402661
TI - Tuning Magnetic Anisotropy Through Ligand Substitution in Five-Coordinate Co(II)
Complexes.
AB - Understanding the origin of magnetic anisotropy and having the ability to tune it
are essential needs of the rapidly developing field of molecular magnetism. Such
attempts at determining the origin of magnetic anisotropy and its tuning are
still relatively infrequent. One candidate for such attempts are mononuclear
Co(II) complexes, some of which have recently been shown to possess slow
relaxation of their magnetization. In this contribution we present four different
five-coordinated Co(II) complexes, 1-4, that contain two different "click"
derived tetradentate tripodal ligands and either Cl- or NCS- as an additional,
axial ligand. The geometric structures of all four complexes are very similar.
Despite this, major differences are observed in their electronic structures and
hence in their magnetic properties as well. A combination of temperature
dependent susceptibility measurements and high-frequency and -field EPR (HFEPR)
spectroscopy was used to accurately determine the magnetic properties of these
complexes, expressed through the spin Hamiltonian parameters: g-values and zero
field splitting (ZFS) parameters D and E. A combination of optical d-d absorption
spectra together with ligand field theory was used to determine the B and Dq
values of the complexes. Additionally, state of the art quantum chemical
calculations were applied to obtain bonding parameters and to determine the
origin of magnetic anisotropy in 1-4. This combined approach showed that the D
values in these complexes are in the range from -9 to +9 cm-1. Correlations have
been drawn between the bonding nature of the ligands and the magnitude and sign
of D. These results will thus have consequences for generating novel Co(II)
complexes with tunable magnetic anisotropy and hence contribute to the field of
molecular magnetism.
PMID- 28402662
TI - Dominant Carbons in trans- and cis-Resveratrol Isomerization.
AB - A comprehensive analysis for isomerization of geometric isomers in the case of
resveratrol (R) has been presented. As an important red wine molecule, only one
geometric isomer of resveratrol, i.e., trans-R rather than cis-R, is primarily
associated with health benefit. In the present study, density function theory
(DFT) provides accurate descriptions of isomerization of resveratrol. The nearly
planar trans-R forms a relatively rigid and less flexible conjugate network, but
the nonplanar cis-R favors a more flexible structure with steric through space
interaction. The calculated carbon nuclear magnetic resonance (NMR) chemical
shift indicates that all carbons are different in the isomers; it further reveals
that four carbon sites, i.e., C(6), C(8)?C(9), and C(11), have a significant
response to the geometric isomerization. Here C(6) is related to the steric
effect in cis-R, whereas C(11) may indicate the isomerization proton transfer on
C(9) linking with the resorcinol ring. The excess orbital energy spectrum (EOES)
confirms the NMR "bridge of interest" carbons and reveals that five valence
orbitals of 34a, 35a, 46a, 55a, and 60a respond to the isomerization most
significantly. The highest occupied molecular orbital (HOMO), 60a, of the isomer
pair is further studied using dual space analysis (DSA) for its orbital momentum
distributions, which exhibit p-electron dominance for trans-R but hybridized sp
electron dominance for cis-R. Finally, energy decomposition analysis (EDA)
highlights that trans-R is preferred over cis-R by -4.35 kcal.mol-1, due to small
electrostatic energy enhancement of the attractive orbital energy with respect to
the Pauli repulsive energy.
PMID- 28402663
TI - Reaction Mechanism of 4-Chlorobiphenyl and the NO3 Radical: An Experimental and
Theoretical Study.
AB - Experiment and theoretical chemistry calculations were conducted to elucidate the
mechanism of the reaction between 4-chlorobiphenyl (4-CB) and the NO3 radical.
The degradation of PCBs was investigated mechanistically through transient
absorption spectroscopy technology and high-accuracy theoretical calculation by
using 4-CB as the model. Laser flash photolysis (LFP) experiments were performed
at 355 nm. The main intermediate was analyzed through transient absorption
spectroscopy and identified to be a charge transfer complex (CTC). The final
products were identified through GC-MS analysis. The ground states and excited
states of the reactants were calculated through density functional theory (DFT)
method. The absorption bands at 400 and 700 nm show good agreement with the
experimental results. The ratio of absorbance at 400 and 700 nm is 1.6, and the
experimental value is 1.8. Analysis of the charge population indicated that one
unit charge transfer from 4-CB to NO3. The entire reaction process was divided
into two phases. In the first phase, the CTC intermediate was formed by
electrostatic attraction between 4-CB and the NO3 radical. In the second phase,
the most important channel of subsequent reactions is the sigma-complex as an
intermediate formed by N-C coupling. The final product 4-chloro,2-nitrobiphenyl
was generated with the breakage of BC-H and BN-O, and benzene derivatives were
formed by other channels.
PMID- 28402664
TI - 1,4-Dicarbofunctionalization of 4-Fluoroaryl Grignard and Lithium Reagents with
Disubstituted Malononitriles.
AB - An efficient one-pot 1,4-dicarbofunctionalization of 4-fluoroaryl Grignard or
lithium reagents with 2,2-disubstituted malononitriles is described. The reaction
proceeds by sequential transnitrilation and SNAr reactions. Commercial Grignard
solutions, Grignard reagents prepared in situ by halogen/magnesium exchange with
i-PrMgCl, or aryllithium reagents prepared in situ by bromine/lithium exchange
with n-BuLi are compatible with the reaction conditions. Moreover, 2,2
disubstituted malononitriles of diverse structures are accommodated. The reaction
provides a unique approach to 1,4-dicarbofunctionalization of activated arenes in
a tandem, one-pot transformation.
PMID- 28402665
TI - Kinetic Modeling of the Thermal Destruction of Nitrogen Mustard Gas.
AB - The destruction of stockpiles or unexploded ammunitions of nitrogen mustard
(tris(2-chloroethyl)amine, HN-3) requires the development of safe processes. The
thermal destruction of this kind of compound is one of the most efficient method
of destruction. Because of the high-level of toxicity of this chemical, there is
a considerable lack of knowledge on the chemical kinetics at high temperatures.
In this study, a detailed chemical kinetic model for the pyrolysis of nitrogen
mustard gas is developed based on a large number of thermokinetic parameters
calculated with theoretical chemistry. The thermal decomposition of HN-3 is shown
to mainly proceed through stepwise dechlorination with Cl-atom being the
principal chain carrier. The successive losses of chlorine atom mainly lead to
unsaturated amines without chlorine groups. Theoretical calculations demonstrated
that the thermal decomposition of these compounds ultimately lead to the
formation of pyrrole, which can accumulate at low temperature. At higher
temperatures, pyrrole yields HCN and acetylene. Simulations also predict that
about 52% of the total flux of decomposition of HN-3 leads to the formation of
N,N-diethenyl-2-chloroethylamine (P29), which acts as a chain branching agent
because its unimolecular decomposition is preponderant and produces one chlorine
and one hydrogen atoms. Comparisons with the simulated reactivity of sulfur
mustard gas are also performed and show that HN-3 is more reactive that the
former toxic. The higher number of chlorine atoms in HN-3 compared to sulfur
mustard (3 vs 2) and the formation of the chain branching intermediate P29 during
its decomposition explain this behavior.
PMID- 28402667
TI - Exploring Cation-pi Interaction in the Complexes with B=B Triple Bond: A DFT
Study.
AB - Density functional theory calculations on metal ion-pi interactions in cation-pi
complexes of diboryne and sandwiches of diboryne and benzene formed via metal
ions were performed to understand the strength of interaction in these complexes.
Results suggest that apart from the smaller metal ions (Li+, Be2+), larger ions
(Na+, Mg2+, Ca2+, and Al3+) can also form cation-pi complexes with B=B triple
bond and interaction energies of the complexes with larger metal ions (possessing
same charges) are less than those obtained with smaller ions. Cations with higher
charge lead to stronger interaction with the B=B triple bonds. The calculated
interaction energy further reveals that the sandwiches are more stable than their
corresponding cation-pi complexes. Stability of the complexes is measured in
terms of global hardness (using Koopmans' theorem and DeltaSCF method), and the
values obtained using DeltaSCF method corroborate with the stability trend
predicted by interaction energy values. Negative solvent-phase interaction energy
for most of the chosen complexes indicates their stability in polar solvents too.
PMID- 28402666
TI - BaAu2S2: A Au-Based Intrinsic Photocatalyst for High-Performance Visible-Light
Photocatalysis.
AB - A new Au-based sulfide BaAu2S2 was obtained through solid-state reaction. It
crystallizes in the tetragonal space group I41/amd with unit cell parameters of a
= 6.389 72(2) A, b = 6.389 72(2) A, c = 12.7872(1) A, and Z = 4. Its structure
features [AuS2/2]infinity zigzag chains composed of corner-sharing AuS2 linear
units. With a direct band gap of 2.49 eV, BaAu2S2 is suitable for the visible
light harvesting. Moreover, it exhibits excellent visible-light photocatalytic
activity, which is 1.3 times that of graphitic carbon nitride (g-C3N4) and also
demonstrates excellent circulating stability. On the basis of the crystal and
electronic structure analysis, the electrons are highly delocalized along the
[AuS2/2] chains, and the electron effective mass of BaAu2S2 is only approximately
one-fifth of that of g-C3N4, which may help the separation of the electron/hole
pairs during the photocatalytic process. Additionally, the absorption coefficient
of BaAu2S2 is extremely high, exceeding 1 * 104 cm-1 over the entire absorbable
visible spectrum (hnu > Eg), which is significantly higher than that of g-C3N4.
Such factors may contribute to its outstanding photocatalytic performances.
According to our best knowledge, BaAu2S2 is the first noble metal-based
chalcogenide photocatalyst reported as intrinsic light-harvesting and
electron/hole-generating centers. This study may provide valuable insights for
further research on photocatalytic materials.
PMID- 28402668
TI - Highly Stable Silica-Coated Gold Nanoflowers Supported on Alumina.
AB - Shape-controlled nanocrystals, such as nanowires and nanoflowers, are attractive
because of their potential novel optical and catalytic properties. However, the
dispersion and morphological stabilities of shape-controlled nanocrystals are
easily destroyed by changing the dispersion solvent and temperature. Methods of
support and the silica coating are known to improve the dispersion and
morphological stabilities of metal nanocrystals. The silica-coating method often
causes morphological changes in shape-controlled nanocrystals because the silica
coating is formed in mixed solutions of water and organic solvents such as
ethanol, and this results in aggregation due to changes in the dispersion
solvent. Furthermore, ligand exchange, designed to improve the dispersion
stability in the solvent, often causes morphological changes. This article
introduces a method for the preparation of highly stable silica-coated Au
nanoflowers (AuNFs) supported on Al2O3. The method of support prevents the
aggregation and precipitation of AuNFs when the solvent is changed from water to
water/ethanol. Through stability improvement, silica coating of AuNFs/Al2O3 was
conducted in water/ethanol without ligand exchange that causes morphological
changes. Furthermore, silica-coated AuNFs/Al2O3 exhibit high morphological
stability under high-temperature conditions compared to uncoated AuNFs/Al2O3.
These results are very useful when preparing highly morphologically stable,
silica-coated, shape-controlled nanocrystals without ligand exchange.
PMID- 28402669
TI - N-Trifluoromethylation of Nitrosoarenes with Sodium Triflinate.
AB - A highly efficient N-trifluoromethylation of nitrosoarenes is reported. The
inexpensive and convenient Langlois reagent (sodium triflinate) is employed as a
CF3-radical source in combination with a copper catalyst and an oxidant. N
Trifluoromethylated hydroxylamines are obtained in high yields within 1 h at room
temperature. The addition of hydroquinone was found to be instrumental to prevent
the formation of side products. The method is high-yielding, is scalable, and
displays a high functional group tolerance.
PMID- 28402670
TI - Controllably Manipulating Three-Dimensional Hybrid Nanostructures for Bulk
Nanocomposites with Large Energy Products.
AB - Hybrid nanostructures that comprise two or more nanoscale functional components
are fascinating for applications in electronics, energy conversion devices, and
biotechnologies. Their performances are strongly dependent on the characteristics
of the individual components including the size, morphology, orientation, and
distribution. However, it remains challenging to simultaneously control these
structural properties in a three-dimensional (3D) hybrid nanostructure. Here, we
introduce a robust strategy for concurrently manipulating these characteristics
in a bulk SmCo/Fe(Co) nanocomposite. This method can tune nanocrystals in size
(down to sub-10 nm), morphology (sphere, rod, or disc), and crystallographic
orientation (isotropic or anisotropic). We have therefore achieved the desired
nanostructures: oriented hard magnetic SmCo grains and homogeneously distributed
soft magnetic Fe(Co) grains with high fractions (~26 wt %) and small sizes (~12.5
nm). The resulting anisotropic nanocomposite exhibits an energy product that is
approximately 50% greater than that of its corresponding pure SmCo magnet and 35%
higher than the reported largest value in isotropic SmCo/Fe(Co) systems. Our
findings pave a new way to manipulating 3D hybrid nanostructures in a
controllable manner.
PMID- 28402671
TI - Highly Enantioselective Construction of Hajos-Wiechert Ketone Skeletons via an
Organocatalytic Vinylogous Michael/Stetter Relay Sequence.
AB - A highly enantioselective supramolecular iminium-catalyzed vinylogous Michael
addition/Stetter relay sequence has been developed. This transformation provided
a series of Hajos-Wiechert-type fused bicyclic diones with three continuous
stereogenic centers in good yields with excellent enantioselectivities. The
obtained products can be easily transformed into other structures with potential
synthetic value.
PMID- 28402672
TI - A Modular Implementation for the Simulation of 1D and 2D Solid-State NMR Spectra
of Quadrupolar Nuclei in the Virtual Multifrequency Spectrometer-Draw Graphical
Interface.
AB - We present the implementation of the solid state (SoS)NMR module for the
simulation of several 1D and 2D NMR spectra of all the elements in the periodic
table in the virtual multifrequency spectrometer (VMS). This module is fully
integrated with the graphical user interface of VMS (VMS-Draw) [Licari et al., J.
Comput. Chem. 36, 2015, 321-334], a freeware tool which allows a user-friendly
handling of structures and analyses of advanced spectroscopical properties of
chemical compounds-from model systems to real-world applications. Besides the
numerous modules already available in VMS for the study of electronic, optical,
vibrational, vibronic, and EPR properties, here the simulation of NMR spectra is
presented with a particular emphasis on those techniques usually employed to
investigate solid state systems. The SoSNMR module benefits from its ability to
work under both periodic and nonperiodic conditions, such that small
molecules/molecular clusters can be treated, as well as extended three
dimensional systems enforcing (or not) translational periodicity. These features
allow VMS to simulate spectra resulting from NMR calculations by some popular
quantum chemistry codes, namely Gaussian09/16, Castep, and Quantum Espresso. The
effectiveness of the SoSNMR module of VMS is examined throughout the manuscript,
and applied to simulate 1D static, MAS, and VAS NMR spectra as well as 2D
correlation (90 degrees , MAS) and MQMAS spectra of active NMR nuclei embedded in
different amorphous and crystalline systems of actual interest in chemistry and
material science. Finally, the program is able to simulate the spectra of both
the total ensemble of spin-active nuclei present in the system and of
subensembles differentiated depending on the chemical environment of the first
and second coordination sphere in a very general way applicable to any kind of
systems.
PMID- 28402673
TI - Functionalized Lipid-Polymer Hybrid Nanoparticles Mediated Codelivery of
Methotrexate and Aceclofenac: A Synergistic Effect in Breast Cancer with Improved
Pharmacokinetics Attributes.
AB - The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac
(ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to
achieve target specific and controlled delivery for developing therapeutic
interventions against breast cancer. The effective combination therapy requires
coadministration of drugs to achieve synergistic effect on tumor with minimum
adverse effects. Present study investigates the potential of codelivery of MTX
and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB
231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle
size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL
was calculated as 85-90% and 10-12%, respectively. The coumarin-6 LPHNP
formulations showed rapid internalization within 2 h incubation with MCF-7 and
MDA-MB-231 cells. With 8-10 times, greater bioavailability of drug-loaded LPHNPs
than free MTX and ACL was obtained. Also, antitumor efficacy of MTX- and ACL
loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse
model. This model showed better control over tumor growth with MTX- and ACL
loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs
showed prophylactic and anticancer activity in DMBA-induced mouse model at higher
dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when
administered in combination with MTX. In conclusion, ACL enhances the therapeutic
and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs,
as confirmed by cell viability and serum angiogenesis (IL-6, TNF-alpha, IL-1beta,
COX2, and MMP1) at both transcript and proteome level.
PMID- 28402674
TI - Toward Highly Efficient Electrocatalyst for Li-O2 Batteries Using Biphasic N
Doping Cobalt@Graphene Multiple-Capsule Heterostructures.
AB - For the promotion of lithium-oxygen batteries available for practical
applications, the development of advanced cathode catalysts with low-cost, high
activity, and stable structural properties is demanded. Such development is
rooted on certain intelligent catalyst-electrode design that fundamentally
facilitates electronic and ionic transport and improves oxygen diffusivity in a
porous environment. Here we design a biphasic nitrogen-doped cobalt@graphene
multiple-capsule heterostructure, combined with a flexible, stable porous
electrode architecture, and apply it as promising cathodes for lithium-oxygen
cells. The biphasic nitrogen-doping feature improves the electric conductivity
and catalytic activity; the multiple-nanocapsule configuration makes high/uniform
electroactive zones possible; furthermore, the colander-like porous electrode
facilitates the oxygen diffusion, catalytic reaction, and stable deposition of
discharge products. As a result, the electrode exhibits much improved
electrocatalytic properties associated with unique morphologies of
electrochemically grown lithium peroxides.
PMID- 28402675
TI - Mechanistic Insight into the Molecular TiO2-Mediated Gas Phase Detoxication of
DMMP: A Theoretical Approach.
AB - The detoxication of DMMP (dimethyl methylphosphonate) mediated by molecular TiO2
has been investigated computationally using density functional theory (DFT). From
our previous studies, it is evident that the unimolecular detoxication of OPCs
(organophosphorus compounds) is kinetically unfeasible at room temperature due to
the significantly high activation barrier. Thus, the aim of our work is to find
out whether molecular TiO2 can make any significant impact on the kinetic
feasibility of the detoxication processes or not. Here, we have identified a
total of three detoxication pathways, where in the first step the detoxication
occurs through H-abstraction with the assistance of TiO2, and in the second step,
the titanium complex is separated from the respective phospho-titanium complexes.
The outcomes reveal that the TiO2-mediated detoxication pathways are at least
20.0 kcal/mol more favorable than their respective unimolecular pathways and that
among them, the alpha-H-mediated isomerization is found to be the most feasible
pathway. When the separation of a titanium complex is under consideration, the
double H2O-assisted mechanism is found to be the favored pathway. Overall, the
entire work provides a widespread idea about the efficiency of molecular TiO2
assisted detoxication of DMMP, which can be well applicable to other OPCs also.
PMID- 28402676
TI - Optimizing the Parameters Governing the Fragmentation of Cross-Linked Peptides in
a Tribrid Mass Spectrometer.
AB - We compared the five different ways of fragmentation available on a tribrid mass
spectrometer and optimized their collision energies with regard to optimal
sequence coverage of cross-linked peptides. We created a library of
bis(sulfosuccinimidyl)suberate (BS3/DSS) cross-linked precursors, derived from
the tryptic digests of three model proteins (Human Serum Albumin, creatine
kinase, and myoglobin). This enabled in-depth targeted analysis of the
fragmentation behavior of 1065 cross-linked precursors using the five
fragmentation techniques: collision-induced dissociation (CID), beam-type CID
(HCD), electron-transfer dissociation (ETD), and the combinations ETciD and
EThcD. EThcD gave the best sequence coverage for cross-linked m/z species with
high charge density, while HCD was optimal for all others. We tested the
resulting data-dependent decision tree against collision energy-optimized single
methods on two samples of differing complexity (a mix of eight proteins and a
highly complex ribosomal cellular fraction). For the high complexity sample the
decision tree gave the highest number of identified cross-linked peptide pairs
passing a 5% false discovery rate (on average ~21% more than the second best,
HCD). For the medium complexity sample, the higher speed of HCD proved decisive.
Currently, acquisition speed plays an important role in allowing the detection of
cross-linked peptides against the background of linear peptides. Enrichment of
cross-linked peptides will reduce this role and favor methods that provide
spectra of higher quality. Data are available via ProteomeXchange with identifier
PXD006131.
PMID- 28402677
TI - Multiplex Polymerase Chain Reaction for Identification of Shigellae and Four
Shigella Species Using Novel Genetic Markers Screened by Comparative Genomics.
AB - In the detection of Shigella species using molecular biological methods,
previously known genetic markers for Shigella species were not sufficient to
discriminate between Shigella species and diarrheagenic Escherichia coli. The
purposes of this study were to screen for genetic markers of the Shigella genus
and four Shigella species through comparative genomics and develop a multiplex
polymerase chain reaction (PCR) for the detection of shigellae and Shigella
species. A total of seven genomic DNA sequences from Shigella species were
subjected to comparative genomics for the screening of genetic markers of
shigellae and each Shigella species. The primer sets were designed from the
screened genetic markers and evaluated using PCR with genomic DNAs from Shigella
and other bacterial strains in Enterobacteriaceae. A novel Shigella quintuplex
PCR, designed for the detection of Shigella genus, S. dysenteriae, S. boydii, S.
flexneri, and S. sonnei, was developed from the evaluated primer sets, and its
performance was demonstrated with specifically amplified results from each
Shigella species. This Shigella multiplex PCR is the first to be reported with
novel genetic markers developed through comparative genomics and may be a useful
tool for the accurate detection of the Shigella genus and species from closely
related bacteria in clinical microbiology and food safety.
PMID- 28402678
TI - Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness
of Endometrial Cancer Cells.
AB - Tamoxifen treatment in breast cancer patients is associated with increased risk
of endometrial malignancies. Significantly, higher AGR2 expression was found in
endometrial cancers that developed in women previously treated with tamoxifen
compared to those who had not been exposed to tamoxifen. An association of
elevated AGR2 level with myometrial invasion occurrence and invasion depth was
also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular
proliferation. Although adverse tamoxifen effects on endometrial cells remain
elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent
mechanism of action responsible for increased incidence of endometrial cancer.
PMID- 28402679
TI - Inhibition of osteogenesis surrounding the titanium implant by CGRP deficiency.
AB - Previous studies have suggested one of the neurotransmitters, calcitonin gene
related peptide (CGRP), modulates local regulation of bone metabolism; however,
the regulating signaling pathway is still being explored. The objective of this
study was to determine whether CGRP deficiency affects the osteogenesis
surrounding titanium implants in vivo. Titanium screws were implanted in 72 adult
rats, which were divided into three groups randomly: Sham, inferior alveolar
neurectomy (IAN), and IAN+CGRP. Saline solution containing CGRP (concentration:
100 nmol/L) was injected into the area surrounding the implants in the IAN+CGRP
group every day post operation. According to histological observations and Micro
CT, osteogenesis surrounding the implant was suppressed in the IAN group compared
to that in the Sham and IAN+CGRP groups; the highest degree of osteogenesis was
observed in the Sham group. This effect was also proved via the gene expressions
of osteocalcin and runt-related transcription factor 2 surrounding the implant by
real-time (RT) PCR analysis. In addition, through immunofluorescence staining and
RT-PCR analysis, levels of CGRP and beta-catenin were also reduced in the IAN
group, while the highest expression was observed in the Sham group (p < 0.05).
Our results collectively suggest that the titanium implant bone model established
by IAN exhibited CGRP deficiency and reduced osteogenesis surrounding the
implant. Additionally, the expression analyses suggest that the canonical Wnt
signaling pathway could be involved in this process of bone metabolism in vivo.
PMID- 28402680
TI - Corrigendum.
PMID- 28402681
TI - Characterization of oligonucleotide aptamers targeting the 5'-UTR from dengue
virus.
AB - AIM: The dengue virus is responsible for a high worldwide incidence of
infections, aggravated by late diagnosis, and often confused with other tropical
diseases. Results/methodology: Oligonucleotide aptamers binding to the 5'-UTR
from dengue virus selected after eight rounds by systematic evolution of ligands
by exponential enrichment technology were analyzed by dot-blot assay and in
silico prediction of secondary structures, demonstrating the presence of stem
loops that may have the potential for interaction with the viral genome, which
can lead to loss of their original conformation. CONCLUSION: This is the first
description of RNA aptamers against functional RNA elements of the dengue virus
genome with implications for disease control, which may have potential as tools
in the future of antiviral therapies and for diagnostics.
PMID- 28402682
TI - Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up
observational study.
AB - BACKGROUND: The psychoactive indole alkaloid ibogaine has been associated with
encouraging treatment outcomes for opioid dependence. The legal status of
ibogaine in New Zealand provides a unique opportunity to evaluate durability of
treatment outcomes. OBJECTIVE: To examine longitudinal treatment effects over a
12-month period among individuals receiving legal ibogaine treatment for opioid
dependence. METHOD: This observational study measured addiction severity as the
primary outcome in 14 participants (50% female) over 12 months post-treatment
using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine
treatment by either of two treatment providers. Secondary effects on depression
were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective
Opioid Withdrawal Scale (SOWS) was collected before and immediately after
treatment to measure opioid withdrawal symptoms. RESULTS: Nonparametric
comparisons via Friedman Test between baseline and 12-month follow-up for
participants completing all interviews (n = 8) showed a significant reduction for
the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores
from baseline to 12-month follow-up were also significant (p < 0.001).
Significant reductions in SOWS scores for all participants (n = 14) were also
observed acutely after treatment (p = 0.015). Patients with partial data (n = 4)
also showed reductions in ASI-Lite drug use scores and family/social status
problems. One patient enrolled in the study died during treatment. CONCLUSION: A
single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid
cessation or sustained reduced use in dependent individuals as measured over 12
months. Ibogaine's legal availability in New Zealand may offer improved outcomes
where legislation supports treatment providers to work closely with other health
professionals.
PMID- 28402683
TI - Improving Quality Management in Medicine: Is It "Catch 22" All Over Again?
PMID- 28402685
TI - Extending 'predict first' to the design-make-test cycle in small-molecule drug
discovery.
PMID- 28402684
TI - A Nonsense ALMS1 Mutation Underlies Alstrom Syndrome in an Extended Mennonite
Kindred Settled in North Mexico.
AB - AIM: Alstrom syndrome (AS) is a rare autosomal recessive multisystem disease
caused by biallelic mutations in ALMS1, a gene encoding a widely expressed
centrosomal/basal body protein. Although more than 200 pathogenic mutations in
ALMS1 have been identified to date in AS patients from various ethnic
populations, there are very few reports of ALMS1 founder mutations in isolated
populations. Our aim was to describe the molecular characterization of a cohort
of AS patients from an extended inbred Mennonite kindred settled in Mexico.
METHODS: Genetic study included polymerase chain reaction amplification and
direct nucleotide sequencing of the entire ALMS1 gene in DNA from seven related
AS patients. RESULTS: A homozygous single-nucleotide c.10480C>T substitution in
exon 16, predicting a p.Q3494* nonsense mutation, was identified in all affected
subjects. CONCLUSIONS: To our knowledge, this is the first demonstration of a
high prevalence of AS in Mennonites, a population group maintaining high levels
of consanguineous marriage in their communities. Our findings provide an example
of genetic isolation and consanguinity causing a high prevalence of AS and offer
the opportunity for early clinical interventions and for genetic counseling of at
risk couples in this community.
PMID- 28402686
TI - The creation and implementation of an outpatient pulmonary embolism treatment
protocol.
AB - The ability to rapidly and accurately risk-stratify patients with venous
thromboembolism (VTE), and the availability of direct acting oral anticoagulants
have reduced the need for intravenous anticoagulation for patients with deep vein
thrombosis (DVT) and pulmonary embolism (PE). Emergency physicians are generally
reluctant to discharge patients with VTE without defined and reliable follow up
in place, and VTE patients treated with anticoagulants can be at risk for
complications related to recurrent VTE and bleeding. In addition, screening for
associated diseases (e.g. cancer, hypercoagulable states) may be indicated.
Therefore, the outpatient treatment of low risk VTE requires coordinated effort
and reliable follow up. By leveraging detailed outcome data and collaborative
relationships, we have created a protocol for the safe outpatient treatment of
patients with low risk DVT and PE. Our protocol is data driven and designed to
address barriers to outpatient VTE management. We expect our protocol to result
in improved patient satisfaction, more efficient emergency department (ED)
throughput, and decreased cost. Applied nationally, the outpatient treatment of
select patients with DVT and PE could have major public health and economic
impact.
PMID- 28402688
TI - The potential of irisin as a therapeutic for diabetes.
PMID- 28402687
TI - Seat belt pre-pretensioner effect on child-sized dummies during run-off-road
events.
AB - OBJECTIVE: Run-off-road events occur frequently and can result in severe
consequences. Several potential injury-causing mechanisms can be observed in the
diverse types of run-off-road events. Real-world data show that different types
of environments, such as rough terrain, ditch types, and whether multiple events
occur, may be important contributing factors to occupant injury. Though
countermeasures addressing front seat occupants have been presented, studies on
rear seat occupant retention in situations such as run-off-road events are
lacking. The aim of this study was to investigate the seat belt pre-pretensioner
effect on rear-seated child-sized anthropomorphic test devices (ATDs) during 2
different types of run-off-road events. METHODS: The study was carried out using
2 test setups: a rig test with a vehicle rear seat mounted on a multi-axial robot
simulating a road departure event into a side ditch and an in-vehicle test setup
with a Volvo XC60 entering a side ditch with a grass slope, driving inside the
ditch, and returning back to the road from the ditch. Potential subsequent
rollovers or impacts were not included in the test setups. Three different ATDs
were used. The Q6 and Q10 were seated on an integrated booster cushion and the
Hybrid III (HIII) 5th percentile female was positioned directly on the seat. The
seat belt retractor was equipped with a pre-pretensioner (electrical reversible
retractor) with 3 force level settings. In addition, reference tests with the pre
pretensioner inactivated were run. Kinematics and the shoulder belt position were
analyzed. RESULTS: In rig tests, the left-seated ATD was exposed to rapid inboard
lateral loads relative to the vehicle. The displacement for each ATD was reduced
when the pre-pretensioner was activated compared to tests when it was
inactivated. Maximum inboard displacement occurred earlier in the event for all
ATDs when the pre-pretensioner was activated. Shoulder belt slip-off occurred for
the Q6 and Q10 in tests where the pre-pretensioner was inactivated. During in
vehicle tests, the left-seated ATD was exposed to an inboard movement when
entering the road again after driving in the ditch. The maximum inboard head
displacement was reduced in tests where the pre-pretensioner was activated
compared to tests in which it was inactivated. CONCLUSIONS: During both test
setups, the activation of the pre-pretensioner resulted in reduced lateral
excursion of the Q6, Q10, and HIII 5th percentile female due to the shoulder belt
remaining on the shoulder and supporting the side of the lower torso. The results
provide new insights into the potential benefits of using a pre-pretensioner to
reduce kinematic responses during complex run-off-road events through supporting
the seat belt to remain on the shoulder. This study addresses potential
countermeasures to improve real-world protection of rear-seated children, and it
provides a broader perspective including the influence of precrash kinematics.
PMID- 28402689
TI - The molecular mechanisms of preventing apoptosis of cartilage chondrocyte to
target osteoarthritis.
PMID- 28402690
TI - Reduction of Abdominal Adhesions with Elecrospun Fiber Membranes in Rat Models.
AB - PURPOSE: The aim of this study was to assess the effects three electrospun fiber
membranes on postoperative adhesion formation in rat surgical models. MATERIALS
AND METHODS: The PEG-PHBV (polyethylene glycol and poly-beta-hydroxybutyrate
valerate), PLA(Polylactic acid) and CS-PEG(chitosan and polyethylene glycol) were
used for submicrometric membranes fabrication by electrospinning. A total of 64
SD male rats were randomly divided into 4 groups, one control group and 3
treatment groups, each consisting of 16 rats. The rats were underwent median
laparotomy and standardized abrasion of the cecum. The indicated membranes were
applied intraperitoneally at the end of the surgical procedure in the treatment
groups, while the controls left without treatment. Two and four weeks after
surgery respectively, a relaparotomy was made for adhesion grading and
histopathological examination, Hydroxyproline (Hyp) levels at the adhesion sites
in each group were measured. RESULTS: The electrospun submicrometric membranes
significantly reduced not only the incidence of adhesion but also the adhesion
grading scales (p < 0.05 compared to the control group) at both two weeks and
four weeks after the initial operation. Furthermore, the fibrosis grades were
also higher in control groups as compared with the submicrometric membrane
groups. Hyp levels in the control group was significant higher than the three
experiment groups at both 2 and 4 weeks time points (p < 0.05). There were no
statistical differences between the different treatment groups at either time
points. CONCLUSIONS: Three electrospun submicrometric membranes were soft,
flexible, easy to handle, and effectively reduced adhesion formation in rat
modes.
PMID- 28402691
TI - Arabidopsis aspartic proteases A36 and A39 play roles in plant reproduction.
AB - Aspartic proteases (Aps, EC3.4.23) are one of the 4 major mechanistic classes of
proteolytic enzymes with the conserved motifs Asp-Thr/Ser-Gly (DT/SG) at the
active site and are activated at acidic pH. In Arabidopsis, 69 genes were
identified as coding putative aspartic proteinases. However, little is known
about most of these enzymes. Recently, we characterized 2 novel Arabidopsis Aps
genes, A36 and A39, which encode 2 putative GPI-anchored pollen-high-expressed
Aps. a36 a39 mutants display significant abortion. The pollen grains underwent
apoptosis-like programmed cell death and the degeneration of female gametes was
also appeared in the a36 a39 mutant. Besides, the pollen tube of a36 a39 has
compromised micropylar guidance. A36 and A39 were membrane-anchored protein and
co-localized with a reported GPI-anchored protein COBRA-LIKE 10 (COBL10). In
apical region of a36 a39 pollen tubes cell wall, the abundance of highly
methlyestered homogalacturonans and xyloglucans were significantly increased.
These results indicated that A36 and A39 are vital factors involved in
gametogenesis and pollen guidance in Arabidopsis.
PMID- 28402692
TI - Racial/Ethnic Differences in Women's Experiences of Reproductive Coercion,
Intimate Partner Violence, and Unintended Pregnancy.
AB - OBJECTIVE: To explore racial/ethnic differences in reproductive coercion (RC),
intimate partner violence (IPV), and unintended pregnancy (UIP). MATERIALS AND
METHODS: We analyzed cross-sectional, baseline data from an intervention that was
conducted between August 2008 and March 2009 in five family planning clinics in
the San Francisco, California area, to examine the association of race/ethnicity
with RC, IPV, and UIP among female patients aged 16-29 (n = 1234). RESULTS: RC
was significantly associated with race/ethnicity, p < 0.001, [prevalence
estimates: Black (37.1%), multiracial (29.2%), White (18.0%), Hispanic/Latina
(24.0%), and Asian/Pacific Islander/other (API/other) (18.4%)]. Race/ethnicity
was not associated with IPV. UIP was more prevalent among Black (50.3%) and
multiracial (47.2%) women, with an overall range of 37.1%-50.3% among all
racial/ethnic groups (p < 0.001). In adjusted analyses, factors associated with
UIP were RC [adjusted odds ratio (AOR) = 1.59, 95% confidence interval (95% CI) =
1.26-2.01] and Black (AOR = 1.63, 95% CI = 1.02-2.60) and API/other (AOR = 1.41,
95% CI = 1.15-1.73) race/ethnicity, which remained significant in the presence of
RC. Race-stratified models revealed that RC increased odds of UIP for White (AOR
= 2.06, 95% CI = 1.45-2.93) and Black women (AOR = 1.72, 95% CI = 1.14-2.60).
CONCLUSIONS: Black and multiracial women seeking care in family planning clinics
have a disproportionately high prevalence of RC and UIP. RC may partially explain
differences in UIP prevalence, with the effect of race/ethnicity slightly
attenuated in RC-adjusted models. However, the impact of RC on risk for UIP was
similar for White and Black women. Findings from this study support the need to
understand and prevent RC, particularly among women of color. Results are
foundational in understanding disparities in RC and UIP that may have
implications for refinement of clinical care.
PMID- 28402693
TI - Heparan sulfate proteoglycans regulate autophagy in Drosophila.
AB - Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of
signaling and molecular recognition at the cell surface and in the extracellular
space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have
profound effects on growth, patterning, and cell survival. The Drosophila
neuromuscular junction provides a tractable model for understanding the
activities of HSPGs at a synapse that displays developmental and activity
dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted
the organization of a specialized postsynaptic membrane, the subsynaptic
reticulum (SSR), and affected the number and morphology of mitochondria. We
provide evidence that these changes result from a dysregulation of macroautophagy
(hereafter referred to as autophagy). Cellular and molecular markers of autophagy
are all consistent with an increase in the levels of autophagy in the absence of
normal HS-chain biosynthesis and modification. HS production is also required for
normal levels of autophagy in the fat body, the central energy storage and
nutritional sensing organ in Drosophila. Genetic mosaic analysis indicates that
HS-dependent regulation of autophagy occurs non-cell autonomously, consistent
with HSPGs influencing this cellular process via signaling in the extracellular
space. These findings demonstrate that HS biosynthesis has important regulatory
effects on autophagy and that autophagy is critical for normal assembly of
postsynaptic membrane specializations.
PMID- 28402694
TI - Serum Phosphate and Retinal Microvascular Changes: The Multi-Ethnic Study of
Atherosclerosis and the Beaver Dam Eye Study.
AB - PURPOSE: Higher levels of serum phosphate are strongly linked to increased risk
of cardiovascular disease and therapies aimed to lower serum phosphate are
employed in the management of patients with chronic kidney disease (CKD). Data
are limited, however, on serum phosphate as a risk factor for microvascular
disease in community-based populations. It is important to determine the impact
of novel risk factors, such as phosphate, on the microvasculature. METHODS: We
conducted a prospective study of 3919 individuals in the Multi-Ethnic Study of
Atherosclerosis (MESA) and 3544 individuals in the Beaver Dam Eye Study (BDES) to
test the associations of serum phosphate with retinopathy and retinal vessel
caliber, and change in retinopathy severity and change in retinal vessel caliber.
RESULTS: Mean (standard deviation) serum phosphate was 3.66 (0.52) mg/dl in the
MESA and 3.77 (0.55) mg/dl in the BDES. In multivariable adjusted models,
phosphate was significantly associated with prevalent retinopathy in the MESA
(Odds Ratio [OR] per 1 mg/dl increase in phosphate, 1.22; Confidence Interval
[CI] 1.02-1.47) and the BDES (OR 1.06; CI 1.01-1.11). In stratified analyses,
these relationships were even stronger and only seen in individuals with diabetes
in both the MESA (OR 1.81; CI 1.30-2.53) and the BDES (OR 1.16; CI 1.05-1.29).
Phosphate was not associated with incident or change in retinopathy severity, nor
any retinal caliber outcome. CONCLUSIONS: Among community-living individuals with
low prevalence of CKD, higher serum phosphate was associated with prevalent
retinopathy in individuals with diabetes. Further longitudinal assessments in
patients with diabetes necessitate further investigation.
PMID- 28402696
TI - Chronic cough and an atypical pattern of peripheral pulmonary opacities: A case
report secondary to suspected drug onset.
AB - INTRODUCTION: Chronic eosinophilic pneumonia (CEP) is an idiopathic interstitial
lung disease with nonspecific symptoms that involves a complex inflammatory
cascade. CASE STUDY: A 36-year-old prisoner with a history of psoriasis presented
with progressive worsening dyspnea, chest pain, and cough. His symptoms started 2
months after starting adalimumab, a tumor necrosis factor (TNF)-inhibitor, for
psoriasis treatment. RESULTS: Initial workup revealed 27% eosinophils on complete
blood count, elevated IgE levels on bronchoalveolar lavage, and bilateral
peripheral lung opacities on imaging. The patient's symptoms and eosinophilia
improved markedly after starting corticosteroids. Based on these findings, the
patient was diagnosed with CEP. CONCLUSION: To our knowledge, this is the first
case of asthma and CEP in a patient taking adalimumab. We suspect adalimumab
unmasked the Th2 cell pathway response that was otherwise suppressed by
psoriasis, a primarily Th1 cell pathway disease. The patient's pulmonary changes
can be attributed to an eosinophilic asthma phenotype with adalimumab putatively
indirectly causing CEP.
PMID- 28402695
TI - UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures.
AB - The 5-methylcytosine (5mC) modification regulates multiple cellular processes and
is faithfully maintained following DNA replication. In addition to DNA
methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger
domain-containing protein 1 (UHRF1) plays an important role in the maintenance of
5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality
in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and
domain architecture, but its biologic function is not clear. Here, we have
generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2
knockout mice are viable, but the adult mice develop frequent spontaneous
seizures and display abnormal electrical activities in brain. Despite no global
DNA methylation changes, 5mC levels are decreased at certain genomic loci in the
brains of Uhrf2 knockout mice. Therefore, our study has revealed a unique role of
UHRF2 in the maintenance of local 5mC levels in brain that is distinct from that
of its paralog UHRF1.
PMID- 28402697
TI - The Prenatal Distress Measure: Adaptation of the Postpartum Distress Measure for
a Prenatal Sample.
AB - BACKGROUND: Pregnancy is a significant transition period for women that can be
markedly stressful. The presence of elevated depressed mood and anxiety during
pregnancy places mothers, fetuses, and neonates at greater risk for developing
biological and psychological difficulties. It appears that no general measures of
distress currently exist that can be used to screen for both prenatal anxiety and
mood. MATERIALS AND METHODS: This study explores the applicability of postpartum
distress measure (PDM), a validated general distress postpartum screening tool,
in a prenatal sample. One hundred ninety pregnant women were recruited from
online websites with themes relevant to pregnancy. Women completed a demographics
questionnaire, the Edinburgh Postnatal Depression Scale, The Mood and Anxiety
Symptom Questionnaire, Full Version, Prenatal Distress Measure (Pre-DM), and
Relationship Assessment Scale. RESULTS: An exploratory factor analysis with
Varimax rotation identified two factors: general distress and obsessive
compulsive symptoms. These two factors formed the basis of the 10-item Pre-DM.
The Pre-DM demonstrated very good reliability, with coefficient alphas of 0.85
for the Pre-DM total score, 0.84 for the general distress scale, and 0.80 for the
obsessive-compulsive symptoms scale. Adequate convergent and discriminant
validity with other established measures was also demonstrated. CONCLUSIONS: Ten
total items were selected for the final Pre-DM and are representative of the two
factors that emerged from the exploratory factor analysis: general distress and
obsessive-compulsive symptoms. It appears that before this study, no measure had
been created for the primary purpose of screening for broad psychosocial distress
during pregnancy. It is hoped that with further research, the Pre-DM will serve
as a screening tool for distress during pregnancy and will be used as a companion
measure to the PDM.
PMID- 28402700
TI - Characterizing novel anti-oncogenic triterpenoids from ganoderma.
PMID- 28402698
TI - Hypervirulence and hypermucoviscosity: Two different but complementary Klebsiella
spp. phenotypes?
AB - Since the hypermucoviscous variants of Klebsiella pneumoniae were first reported,
many cases of primary liver abscesses and other invasive infections caused by
this pathogen have been described worldwide. Hypermucoviscosity is a phenotypic
feature characterized by the formation of a viscous filament >=5 mm when a
bacterial colony is stretched by a bacteriological loop; this is the so-called
positive string test. Hypermucoviscosity appears to be associated with this
unusual and aggressive type of infection, and therefore, the causal strains are
considered hypervirulent. Since these first reports, the terms hypermucoviscosity
and hypervirulence have often been used synonymously. However, new evidence has
suggested that hypermucoviscosity and hypervirulence are 2 different phenotypes
that should not be used synonymously. Moreover, it is important to establish that
a negative string test is insufficient in determining whether a strain is or is
not hypervirulent. On the other hand, hypervirulence- and hypermucoviscosity
associated genes must be identified, considering that these phenotypes correspond
to 2 different phenomena, regardless of whether they can act in synergy under
certain circumstances. Therefore, it is essential to quickly identify the genetic
determinants behind the hypervirulent phenotype to develop effective
methodologies that can diagnose in a prompt and effective way these hypervirulent
variants of K. pneumoniae.
PMID- 28402702
TI - Comparison of the Tight Rope Technique and Clavicular Hook Plate for the
Treatment of Rockwood Type III Acromioclavicular Joint Dislocation.
AB - AIM: Acromioclavicular joint dislocation is one of the most common shoulder
problems and may lead to instability or degenerative changes. The aim of this
study was to compare the clinical outcomes of the Tight Rope system and
clavicular hook plate for Rockwood type III acromioclavicular joint dislocation
in adults. MATERIALS AND METHODS: This was a prospective, randomized study in a
hospital setting. From January 2012 to December 2014, 69 patients with type III
injury were reviewed. Patients were randomly divided into two groups: Group A was
treated using the TightRope system and Group B with the clavicular hook plate.
All participants were followed up for 12 months. Clinical outcomes, radiological
results and postoperative complications were recorded. RESULTS: The length of
incision was significantly shorter in Goup A than that in Group B. The blood loss
of surgery was significantly less in the Group A. Significant difference could be
found between the two groups regarding the Visual Analogue Scale scores one day
after surgery, at the 3 and 12 months follow-up. There were no differences
according to the improvement of the Constant-Murley score and the
coracoclavicular distance between the groups. CONCLUSIONS: The two groups have
similar clinical and radiological outcomes. Both treatments could relieve the
pain of dislocation, improve the function of Acromioclavicular joint and rectify
the coracoclavicular distance measured in plain films. However, the TightRope
system exhibited some advantages in terms of length of incision, blood loss of
surgery, the pain postoperatively and no need for a second surgery.
PMID- 28402703
TI - Molecular Detection of Francisella spp. Among Ticks Attached to Camels in Egypt.
AB - This study was conducted to investigate the possible role of camels and attached
ticks in the epidemiology of Francisella spp. including Francisella tularensis.
For this purpose, a total of 319 ticks (248 Hyalomma dromedarii and 71 Amblyomma
spp.) as well as 100 blood and 50 fecal samples collected from camels were
screened for the presence of Francisella spp. by PCR through amplification of
Francisella 16S rRNA gene. Positive samples were then tested for F. tularensis by
PCR. In addition, serum samples from 75 camel abattoir workers were examined for
the presence of IgG antibodies against F. tularensis using enzyme-linked
immunosorbent assay (ELISA). Of the examined ticks, 15 were positive for
Francisella spp. with prevalence of 4.7%, all positive results were recorded in
Hyalomma dromedarii (6%). Neither blood nor fecal samples from camels yielded
Francisella spp. even camels which carried Francisella spp. positive ticks.
Moreover, F. tularensis could not be detected among Francisella-positive ticks.
Phylogenetic analysis of some Francisella 16S rRNA gene sequences obtained in
this study points out that these sequences are closely related to Francisella
like endosymbionts. In contrast, seroprevalence of F. tularensis antibodies among
examined abattoir workers was 9.3% with significantly high prevalence among
workers frequently exposed to tick bites (20.7%) rather than occasionally exposed
workers (2.2%). In conclusion, however, F. tularensis could not be detected in
this study; the high seroprevalence among camel abattoir workers especially those
frequently exposed to tick bites underlines the possible role of ticks attached
to camels in transmission of tularemia to humans.
PMID- 28402699
TI - Inhibition of retrograde transport modulates misfolded protein accumulation and
clearance in motoneuron diseases.
AB - Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic
lateral sclerosis (ALS), are associated with proteins that because of gene
mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic
to cells. To prevent misfolded protein toxicity, cells activate a protein quality
control (PQC) system composed of chaperones and degradative pathways (proteasome
and autophagy). Inefficient activation of the PQC system results in misfolded
protein accumulation that ultimately leads to neuronal cell death, while
efficient macroautophagy/autophagy-mediated degradation of aggregating proteins
is beneficial. The latter relies on an active retrograde transport, mediated by
dynein and specific chaperones, such as the HSPB8-BAG3-HSPA8 complex. Here, using
cellular models expressing aggregate-prone proteins involved in SBMA and ALS, we
demonstrate that inhibition of dynein-mediated retrograde transport, which
impairs the targeting to autophagy of misfolded species, does not increase their
aggregation. Rather, dynein inhibition correlates with a reduced accumulation and
an increased clearance of mutant ARpolyQ, SOD1, truncated TARDBP/TDP-43 and
expanded polyGP C9ORF72 products. The enhanced misfolded protein clearance is
mediated by the proteasome, rather than by autophagy and correlates with the
upregulation of the HSPA8 cochaperone BAG1. In line, overexpression of BAG1
increases the proteasome-mediated clearance of these misfolded proteins. Our data
suggest that when the misfolded proteins cannot be efficiently transported toward
the perinuclear region of the cells, where they are either degraded by autophagy
or stored into the aggresome, the cells activate a compensatory mechanism that
relies on the induction of BAG1 to target the HSPA8-bound cargo to the proteasome
in a dynein-independent manner.
PMID- 28402704
TI - Endoscopic Papillary Large Balloon Dilation Versus Endoscopic Sphincterotomy for
Retrieval of Large Choledocholithiasis: A Prospective Randomized Trial.
AB - BACKGROUND: Endoscopic sphincterotomy (ES) is the standard technique for common
bile duct (CBD) stone removal. Recently, endoscopic papillary large balloon
dilation (EPLBD) has been shown to be a safe and effective technique for the
removal of large CBD stone. The aim of this study was to determine the
therapeutic outcomes and safety of EPLBD compared with ES for large CBD stone
extraction. PATIENTS AND METHODS: One hundred twenty-four patients with large
bile duct stones were randomized into two groups, the first group included 61
patients subjected to EPLBD and the second group included 63 patients who
underwent ES. We compared the success rate of stone removal, frequency of
mechanical lithotripsy requirement, morbidity, and mortality. RESULTS: Baseline
characteristics were not significantly different. The overall ductal clearance
rate was ultimately similar between the EPLBD group (96.7%) and the ES group
(93.7%) (P = .53), the one session ductal clearance rate was significantly
different (86.9% versus 71.4%; P = .01). Requirement of mechanical lithotripsy
was significantly different between the EPLBD and ES group (9.8% versus 17.5%, P
= .04). There were no differences in complication rates between the EPLBD and ES
group; pancreatitis, 4.9% versus 6.3%; minor hemorrhage, 1.6% versus 6.3%; acute
cholangitis, 3.3% versus 1.9%; and recurrent stones, 3.3% versus 3.2%.
CONCLUSIONS: The therapeutic outcomes of EPLBD for removal of large bile duct
stones are better than those of ES with comparable complication rate. EPLBD is
also recommended for removal of large CBD stone in patients with an underlying
coagulopathy or need for anticoagulation following endoscopic retrograde
cholangiopancreaticography.
PMID- 28402707
TI - Physicians, Firearms, and Free Speech - Overturning Florida's Firearm-Safety Gag
Rule.
PMID- 28402705
TI - Interaction of factor H-binding protein of Streptococcus suis with
globotriaosylceramide promotes the development of meningitis.
AB - Streptococcus suis is an important emerging zoonotic agent that causes acute
bacterial meningitis in humans with high mortality and morbidity. Our previous
work showed that factor H-binding protein (Fhb) contributed to virulence of S.
suis, but the role of Fhb in the development of S. suis meningitis remained
unclear. In this study, we demonstrated for the first time that Fhb contributed
to the traversal of S. suis across the human blood-brain barrier by allelic
exchange mutagenesis, complementation and specific antibody blocking studies. We
also showed that globotriaosylceramide (Gb3), the receptor of Fhb, was involved
in this process and affected S. suis infection-induced activation of myosin light
chain 2 through Rho/ROCK signaling in hCMEC/D3 cells. Using a murine model of S.
suis meningitis, we further demonstrated that Gb3-deficiency prevented the mice
from developing severe brain inflammation or injury. Our results demonstrate that
the Fhb-Gb3 interaction plays an important role in the development of S. suis
meningitis and might be a potential therapeutic target against S. suis infection.
PMID- 28402706
TI - Optimum Operating Room Environment for the Prevention of Surgical Site
Infections.
AB - BACKGROUND: Surgical site infections (SSI), whether they be incisional or deep,
can entail major morbidity and death to patients and additional cost to the
healthcare system. A significant amount of effort has gone into optimizing the
surgical patient and the operating room environment to reduce SSI. METHODS:
Relevant guidelines and literature were reviewed. RESULTS: The modern practice of
surgical antisepsis involves the employment of strict sterile techniques inside
the operating room. Extensive guidelines are available regarding the proper
operating room antisepsis as well as pre-operative preparation. The use of pre
operative antimicrobial prophylaxis has become increasingly prevalent, which also
presents the challenge of opportunistic and nosocomial infections. Ongoing
investigative efforts have brought about a greater appreciation of the surgical
patient's endogenous microflora, use of non-bactericidal small molecules, and pre
operative microbial screening. CONCLUSIONS: Systematic protocols exist for
optimizing the surgical sterility of the operating room to prevent SSIs. Ongoing
research efforts aim to improve the precision of peri-operative antisepsis
measures and personalize these measures to tailor the patient's unique microbial
environment.
PMID- 28402708
TI - Diagnosing Sarcopenia in Male Patients With Cirrhosis by Dual-Energy X-Ray
Absorptiometry Estimates of Appendicular Skeletal Muscle Mass.
AB - BACKGROUND: Ascites in cirrhotic patients interfere with accurate assessment of
skeletal muscle when diagnosing sarcopenia. We hypothesized measurement of
appendicular skeletal muscle index (ASMI) with dual-energy x-ray absorptiometry
(DXA) improves the diagnosis of sarcopenia in cirrhotic patients as ASMI does not
include the fluid-filled abdominal compartment. OBJECTIVE: To evaluate if ASMI is
influenced by ascites, lower limb edema (LLE) and predicts mortality alone or
combined with handgrip strength (HGS) in cirrhotic patients. DESIGN: ASMI, HGS,
and 36-month mortality were obtained in 144 men with cirrhosis. ASMI was compared
before and after paracentesis in 20 men with ascites and to results from 20
matched controls. The prognostic value of ASMI alone and with HGS was tested in a
survival. Survival probabilities were obtained for sarcopenia diagnosed by
standard ASMI and HGS European Working Group on Sarcopenia in Older People
(EWGSOP) cutoffs and a new cutoff calculated from our ASMI + HGS tertiles.
RESULTS: ASMI did not change after paracentesis, was lower in patients than in
controls (P < .001), and was not influenced by LLE (D = 0.30 kg/m2, P = .068; R2
= 2.40%). Mortality was influenced by ASMI and HGS (Pinteraction = 0.028).
Sarcopenia diagnosed by EWGSOP was also diagnosed by our new cutoff; both
predicted mortality with the latter more sensitive for mortality risk prediction
(P = .011). CONCLUSIONS: DXA-measured ASMI is not influenced by ascites or LLE in
cirrhotic patients; can diagnose low skeletal muscle/sarcopenia; and predicts
mortality, particularly when combined with HGS.
PMID- 28402709
TI - How Can We Effectively Engage Physicians in the Deprescribing Process?
PMID- 28402710
TI - When Is Enough?
PMID- 28402711
TI - Prevalence and incidence of drug use among college students: an 8-year
longitudinal analysis.
AB - BACKGROUND: Drug use among college students is associated with adverse academic
and health outcomes and risks to personal safety. OBJECTIVES: This study utilized
data from a longitudinal study to estimate annual prevalence, cumulative lifetime
prevalence, and incidence of ten types of drug use during the eight years after
college entry and the average age of onset of each drug used. METHODS:
Participants (N = 1,253; 52% female) were young adults who were originally
enrolled as first-time, first-year students at a university in the mid-Atlantic
US. Annual personal interviews gathered data about the use of seven illicit drugs
and three prescription drugs used nonmedically. Annual follow-up rates ranged
from 76 to 91%. RESULTS: Marijuana was the most commonly used drug in every year
of the study, with the highest annual prevalence estimates in Year 3 (47%wt). In
Year 8, when the modal age of participants was 25, 29%wt used marijuana during
the past year. Nonmedical use of prescription drugs was more prevalent during
college than in the later years of the study. Although the prevalence of cocaine
and ecstasy use was low (cumulative prevalence estimates of 17%wt and 13%wt,
respectively), incidence for these drugs was particularly high in the later years
of the study. CONCLUSION: Drug use is prevalent among college students, and drug
use persists among young adults, even after many have graduated college. More
attention should be directed at identifying and intervening with students at risk
for drug use to mitigate possible academic, health, and safety consequences.
PMID- 28402712
TI - Investigation of a Staphylococcal Food Poisoning Outbreak from a Chantilly Cream
Dessert, in Umbria (Italy).
AB - On August 28, 2015, a staphylococcal food poisoning outbreak occurred in Umbria,
Italy, affecting 24 of the 42 customers who had dinner at a local restaurant.
About 3 h after ingesting a variety of foods, the customers manifested
gastrointestinal symptoms. Within 24 h of notification from the hospital
emergency department, Sanitary Inspectors of the local Public Health Unit
performed an epidemiological investigation. A retrospective cohort study was
conducted among the customers. Food and environmental samples were collected. Due
to the rapid onset of symptoms (vomiting, diarrhea), the food samples were
analyzed for the presence of toxigenic bacteria and their toxins; nasopharyngeal
swabs were collected from the waiters and cooks. Among the food tested, high
levels of coagulase-positive staphylococci (CPS) (3.4 * 108 CFU/g) and
staphylococcal enterotoxins (2.12 ng SEA/g) were only detected in the Chantilly
cream dessert. CPS were also detected on the surface of a kitchen table (10
CFU/swab), and five food handlers were positive for Staphylococcus aureus. In
total, five enterotoxigenic S. aureus isolates were recovered from three food
handlers, a kitchen surface, and the Chantilly cream dessert. These isolates were
further characterized by biotyping, pulsed-field gel electrophoresis, and
multiplex polymerase chain reaction assays for the detection of eleven
enterotoxin encoding genes (sea, seb, sec, sed, see, seg, seh, sei, sej, sep, and
ser) and three genes involved in antibiotic resistance (mecA, mecC, and mupA).
Three sea-positive strains, isolated from the dessert, environment, and one of
the cooks, had the same pulsed-field gel electrophoresis profile and belonged to
the human biotype, suggesting that the contamination causing the outbreak most
likely originated from a food handler. Moreover, improper storage of the dessert,
at room temperature for about 5 h, permitted microbial growth and SEA production.
This study underlines the importance of both laboratory evidence and
epidemiological data for outbreak investigation.
PMID- 28402713
TI - Optical Biometry Derived Axial Length Measurements Following Intravitreal Anti
Vascular Endothelial Growth Factor Treatment for Macular Edema.
AB - PURPOSE: To evaluate axial length (AL) alterations in patients with macular
disease over the course of intravitreal anti-vascular endothelial growth factor
(anti-VEGF) treatment. METHODS: In this prospective, comparative study, 33
patients with macular edema underwent unilaterally intravitreal anti-VEGF therapy
and were followed for two months; the contralateral eyes were considered as
controls. Central retinal thickness (CRT) was measured with spectral-domain
optical coherence tomography and AL with an IOL-Master optical biometer. RESULTS:
CRT of the treated eyes decreased by 35.33 +/- 65.59 MUm (range, -222.00-67 MUm),
while AL increased by 0.008 +/- 0.062 mm (range, -0.11-0.18 mm). CRT of the
control group decreased by 9.82 +/- 65.40 MUm (range, -203-182 MUm), and AL
increased by 0.011 +/- 0.129 mm (range, -0.20-0.67 mm). No significant
correlation was detected between CRT and AL parameters (rhos=0.026, P=0.882).
CONCLUSIONS: Anti-VEGF administration has no significant impact on optical
biometry-derived AL measurements.
PMID- 28402714
TI - 3D dental image registration using exhaustive deformable models: a comparative
study.
AB - OBJECTIVES: Image registration is commonly used in dental applications for
aligning imaging data sets, which is particularly useful when assessing the
progression or regression of particular pathomorphic conditions. However, due to
the nature of the processed data or the data acquisition process itself, rigid
body registration may be insufficient to accurately align the processed data
sets. In such cases, deformable models are employed. This study presents a
comparison of four well-established deformable models for aligning CBCT volumes.
METHODS: The compared models include the original Demons algorithm, symmetric
forces Demons, diffeomorphic Demons and level-set motion. The compared techniques
are incorporated into a general image registration scheme featuring two distinct
stages: a common, fast, rigid-based alignment for pre-registering the data and a
finer elastic registration phase, based on the four compared deformation models.
RESULTS: The proposed framework was applied to a total of 40 CBCT volume pairs
with known and unknown initial differences. CONCLUSIONS: After both qualitative
and quantitative assessment of the produced aligned data, it was concluded that
the level-set motion method outperformed all other techniques for data pairs with
both unknown initial differences, as well as with known elastic deviations based
on fixed sinusoidal models and B-splines.
PMID- 28402715
TI - Protective Effect of Cordycepin on Experimental Testicular Ischemia/Reperfusion
Injury in Rats.
AB - OBJECTIVE: To investigate the role of cordycepin in testicular
ischemia/reperfusion injury in rats. MATERIALS AND METHODS: Forty Wistar albino
rats were randomly divided into four groups, as follows: group one, control (C);
group two, torsion and ischemia (I); group three: detorsion with ischemia
reperfusion (IR); and group four, detorsion/cordycepin. The rats were then
analyzed macromorphologically and histopathologically, and blood tests were
performed. Specifically, the total oxidant status (TOS) and total antioxidant
status (TAS) were determined, and malondialdehyde (MDA), tumor necrosis factor
(TNF)-alpha, interleukin (IL)-6, and IL-1beta levels were analyzed. In addition,
pyknotic nuclei, spermatozoa, edema, and hemorrhage were assessed. RESULTS: When
the IR and cordycepin groups were compared with the other groups, there was a
statistically significant decrease in TNF-alpha and MDA levels (p < 0.05).
Increased TAS levels were observed in the cordycepin group compared with the
control group. TOS levels were significantly increased in the I and IR groups,
but decreased in the cordycepin group (p < 0.05). Similar effects were observed
in tissue biochemistry analysis. Histopathological evaluations revealed that the
spermatozoa count was decreased in the I and IR groups. However, there was an
increase in the cordycepin group, as well as a statistically significant
difference between the IR and cordycepin groups (p < 0.01). Finally, edema and
inflammation were increased in the I and IR groups, but decreased in the
cordycepin group. CONCLUSIONS: Histological and biochemical findings revealed
that cordycepin protected against IR-induced testicular injury.
PMID- 28402716
TI - Preclinical advances in nasopharyngeal carcinoma treatment.
PMID- 28402718
TI - Prions on the run: How extracellular vesicles serve as delivery vehicles for self
templating protein aggregates.
AB - Extracellular vesicles (EVs) are actively secreted, membrane-bound communication
vehicles that exchange biomolecules between cells. EVs also serve as
dissemination vehicles for pathogens, including prions, proteinaceous infectious
agents that cause transmissible spongiform encephalopathies (TSEs) in mammals.
Increasing evidence accumulates that diverse protein aggregates associated with
common neurodegenerative diseases are packaged into EVs as well. Vesicle-mediated
intercellular transmission of protein aggregates can induce aggregation of
homotypic proteins in acceptor cells and might thereby contribute to disease
progression. Our knowledge of how protein aggregates are sorted into EVs and how
these vesicles adhere to and fuse with target cells is limited. Here we review
how TSE prions exploit EVs for intercellular transmission and compare this to the
transmission behavior of self-templating cytosolic protein aggregates derived
from the yeast prion domain Sup 35 NM. Artificial NM prions are non-toxic to
mammalian cell cultures and do not cause loss-of-function phenotypes.
Importantly, NM particles are also secreted in association with exosomes that
horizontally transmit the prion phenotype to naive bystander cells, a process
that can be monitored with high accuracy by automated high throughput confocal
microscopy. The high abundance of mammalian proteins with amino acid stretches
compositionally similar to yeast prion domains makes the NM cell model an
attractive model to study self-templating and dissemination properties of
proteins with prion-like domains in the mammalian context.
PMID- 28402719
TI - OsPRA2 fine-tunes rice brassinosteroid receptor.
AB - Brassinosteroids (BRs) are a kind of plant hormones that regulate many important
agronomic traits. Although the framework of the BR signaling pathway has been
outlined, detailed working mechanisms at several steps of this pathway,
especially at the BR receptor level, need to be further elucidated. Recently we
have reported that a rice small G protein, OsPRA2, bound to the BR receptor
OsBRI1 at the plasma membrane (PM) and inhibited its kinase activity and its
interaction with the co-receptor OsBAK1, leading to a lower sensitivity to BR
treatment and dephosphorylation of OsBZR1. In this follow-up study, we identified
an OsPRA2-interacting protein through yeast 2 hybrid system, which is annotated
as a C2-domain containing GTPase activating protein (OsGAP1). Overexpression of
OsGAP1 in Arabidopsis resulted in a phenotype mimic to BR-deficiency, implying
that the GTPase activity of OsPRA2 is also involved in regulating BR signaling.
In addition, we observed that, besides colocalizing at the PM, OsPRA2 was also
colocalized with OsBRI1 in small granules near PM, suggesting that the function
of OsPRA2 in vesicle traffic may contribute to the regulation of OsBRI1.
PMID- 28402720
TI - Insulin-Like Growth Factor Binding Protein-Related Protein 1 Inhibit Retinal
Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.
AB - PURPOSE: To explore the inhibitory effect of insulin-like growth factor binding
protein-related protein 1 (IGFBP-rP1) on retinal angiogenesis and its underlying
molecular mechanisms in the mouse model of oxygen-induced retinopathy (OIR).
METHODS: C57BL/6J mice were classified into three groups as control group, OIR
nonintervention group, and OIR intervention group. Postnatal day 12 (P12) mice in
OIR intervention group were received recombinant mouse IGFBP-rP1 (50, 100, and
200 ng/mL) intravitreal injection. Five days later, the proliferative neovascular
responses were estimated by quantifying the new vessel areas in flattening
retinal tissues stained by high molecular fluorescein isothiocyanate-dextran and
counting the numbers of neovascular cell nuclei breaking through the internal
limiting membrane in cross sections. Expressions of phospho-extracellular signal
regulated kinase 1/2 (p-ERK1/2), ERK1/2, and vascular endothelial growth factor
(VEGF) proteins in retinal tissues were assessed by western blot analysis.
RESULTS: Irregular neovascularization, nonperfusion region, and fluorescence
leakage were observed in OIR models. The expression of retinal p-ERK1/2 and VEGF
proteins were significantly upregulated in OIR nonintervention group compared
with control group. The area ratio of retinal new vessels and the number of
neovascular cell nuclei in OIR intervention group both decreased significantly,
following the downregulation of retinal p-ERK1/2 protein expression and VEGF
protein expression in a dose-dependent manner. Moreover, there was no significant
difference in retinal ERK1/2 protein expression. CONCLUSIONS: IGFBP-rP1 inhibits
retinal angiogenesis by blocking ERK signaling pathway and downregulating VEGF
expression in the mouse model of OIR. It highlights the potential importance of
IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization in
the future.
PMID- 28402721
TI - Electronic Surveillance of Surgical Site Infections.
AB - BACKGROUND: Electronic health and administrative data are increasingly being used
for identifying surgical site infections (SSI). We found an unexpectedly high
number of patients who could not be classified definitively as having an
infection or not. To further explore this, we present an electronic
classification algorithm for conservative case finding and identify alterations
that would adapt the method for other purposes. METHODS: Two computer algorithms
were created to identify SSI. One model used a strict National Healthcare Safety
Network (NHSN) based SSI algorithm, which was applied to all discharges from
443,284 all discharges from four hospitals in Manhattan, NY, 2009 through 2012.
The second model used discharges that only had NHSN-defined SSI procedures during
the same period. RESULTS: The strict SSI algorithm was able to classify SSI
status for 27.3% of discharges; there was a high number of indeterminate cases.
In contrast, the modified, less strict model, classified 97.2% of discharges with
NHSN-approved SSI procedures. CONCLUSION: Electronic records provide several
options for aiding with the identification of infections in healthcare settings
and can be tailored to suit specific uses. While algorithms for SSI
classification should reflect the NHSN definition, our research emphasizes how
variations of model building can affect the number of indeterminate cases that
may necessitate manual review.
PMID- 28402722
TI - Prevalence of Diabetic Retinopathy in Urban Slums: The Aditya Jyot Diabetic
Retinopathy in Urban Mumbai Slums Study-Report 2.
AB - OBJECTIVES: The aims of the study were to estimate the prevalence of diabetic
retinopathy (DR) and enumerate history-based risk factors in the urban slums of
Western India. METHODS: The population-based study was conducted in seven wards
of Mumbai urban slums, where we screened 6569 subjects of >= 40 years age, with a
response rate of 98.4%, for type 2 diabetes mellitus (T2DM) based on American
Diabetes Association criteria. All subjects with T2DM underwent dilated 30
degrees seven-field stereo-fundus-photography for DR severity grading based on
modified Airlie House classification. A multivariate logistic regression model
was used to assess the correlation of DR with the history-based risk factors.
RESULTS: The prevalence of DR in the general population of Mumbai urban slums was
1.41% (95% CI 0.59-2.23) and in the T2DM population it was 15.37% (95% CI 8.87
21.87). The positive associations with DR were the longer duration of DM (>= 11
years: OR, 12.77; 95% CI 2.93-55.61) and male gender (OR, 2.05; 95% CI 1.08
3.89); increasing severity of retinopathy was also significantly associated with
longer duration of DM (p < 0.001). However, history of hypertension, family
history of DM, consanguineous marriage and migration status were not associated
with DR in the study population. CONCLUSIONS: The prevalence of DR in the general
population and T2DM subjects were 1.41% and 15.37% respectively in Mumbai urban
slums. Duration of DM and male gender were significantly associated with DR. The
slums in Western India show the trends of urban lifestyle influences similar to
the rest of urban India.
PMID- 28402723
TI - Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.
AB - BACKGROUND: Neuroblastoma (NB) is a common and often lethal cancer of early
childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in
infancy and then rapidly declines, with less than 5% of cases diagnosed in
children and adolescents >= 10 y. There is increasing evidence that NB has unique
biology and an chronic disease course in older children and adolescents, but
ultimately dismal survival. METHODS: We describe a rare constitutional 3p26.3
terminal microdeletion which occurred in an adolescent with NB, with apparently
normal phenotype without neurocognitive defects. We evaluated the association of
expression of genes involved in the microdeletion with NB patient outcomes using
R2 platform. We screened NB patient's tumor cells for CHL1 protein expression
using immunofluorescence. RESULTS: Constitutional and tumor DNA were tested by
array-comparative genomic hybridization and single nucleotide-polymorphism-array
analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb
sub-microscopic constitutional terminal 3p deletion that extended to band p26.3.
The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1
genes were hemizygously deleted, each of these genes encode neuronal cell
adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB
patients, whereas low CHL1 expression characterized 417 NB patients having worse
overall survival. CHL1 protein expression on tumor cells from the patient was
weaker than positive control. CONCLUSION: This is the first report of a
constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p,
indicative of the presence of one or more tumor suppressor genes in this region,
occur frequently in neuroblastoma, our results pave the way to the identification
of one putative NB suppressor genes mapping in 3p26.3.
PMID- 28402724
TI - Carbapenem-resistant Enterobacteriaceae: What we know and what we need to know.
PMID- 28402725
TI - Visualization of PML nuclear import complexes reveals FG-repeat nucleoporins at
cargo retrieval sites.
AB - Selective nuclear import in eukaryotic cells involves sequential interactions
between nuclear import receptors and phenylalanine-glycine (FG)-repeat
nucleoporins. Traditionally, binding of cargoes to import receptors is perceived
as a nuclear pore complex independent event, while interactions between import
complexes and nucleoporins are thought to take place at the nuclear pores.
However, studies have shown that nucleoporins are mobile and not static within
the nuclear pores, suggesting that they may become engaged in nuclear import
before nuclear pore entry. Here we have studied post-mitotic nuclear import of
the tumor suppressor protein PML. Since this protein forms nuclear compartments
called PML bodies that persist during mitosis, the assembly of putative PML
import complexes can be visualized on the surface of these protein aggregates as
the cell progress from an import inactive state in mitosis to an import active
state in G1. We show that these post-mitotic cytoplasmic PML bodies incorporate a
multitude of peripheral nucleoporins, but not scaffold or nuclear basket
nucleoporins, in a manner that depends on FG-repeats, the KPNB1 import receptor,
and the PML nuclear localization signal. The study suggests that nucleoporins
have the ability to target certain nuclear cargo proteins in a nuclear pore
uncoupled state, before nuclear pore entry.
PMID- 28402726
TI - DETECTION AND REPORTING OF RANAVIRUS IN AMPHIBIANS: EVALUATION OF THE ROLES OF
THE WORLD ORGANISATION FOR ANIMAL HEALTH AND THE PUBLISHED LITERATURE.
AB - Pathogens of wildlife can have direct impacts on human and livestock health as
well as on biodiversity, as causative factors in population declines and
extinctions. The World Organization for Animal Health (OIE) seeks to facilitate
rapid sharing of information about animal diseases to enable up-to-date risk
assessments of translocations of animals and animal products. The OIE also
produces manuals of recommended methods to standardize diagnostic testing.
Ranaviruses are important amphibian pathogens that may have spread through
international trade, and infections became notifiable to OIE in 2009. We surveyed
and reviewed published literature for data on sampling, diagnostic testing, and
reporting of ranavirus during 2009-14. We also investigated attitudes and
awareness of the OIE and its recommendations for best practice. We found that
sampling effort is uneven and concentrated in the northern hemisphere. We also
identified citizen science projects that have the potential to improve the
quantity and quality of data on the incidence of ranavirus infection and the
circumstances surrounding disease outbreaks. We found reporting of infection to
be inconsistent: reporting was split between the published literature (where it
was subject to a 2-yr lag) and the OIE with little overlap, results of negative
diagnostic tests were underreported, and scientific researchers lacked awareness
of the role of the OIE. Approaches to diagnostic screening were poorly harmonized
and heavily reliant on molecular methods. These flaws in the mechanisms of
ranavirus detection and reporting hamper the construction of a comprehensive
disease information database.
PMID- 28402727
TI - Seroprevalence and Risk Factors of Toxoplasma gondii in Slaughter Pigs in Shaanxi
Province, Northwestern China.
AB - Toxoplasma gondii is an important food-borne zoonotic protozoan parasite, which
can infect endothermic animals, including pigs. However, data on T. gondii in
slaughter pigs in Shaanxi Province were still lacking. To detect the
seroprevalence and analyze the risk factors of T. gondii infection in slaughter
pigs in Shaanxi Province, Northwestern China, a total of 784 serum samples were
collected from four administrative regions and detected by indirect
hemagglutination test for T. gondii infection. Antibodies to T. gondii were found
in 19.9% (156/784) slaughter pigs. Moreover, the seropositive rate was different
among rearing systems (31% in nonintensive pig farms and 6.7% in intensive pig
farms), genders (19.8% in male and 20.0% in female), and regions (ranging from
6.7% in Shenmu to 38.2% in Zhouzhi). Rearing system and region were identified as
risk factors for T. gondii infection. These results showed that T. gondii is
highly prevalent in slaughter pigs in Shaanxi Province, and it could cause a
serious risk to public health. This study provided fundamental information for
the prevention and control of T. gondii infection in slaughter pigs in China.
PMID- 28402728
TI - Cost and Consequences of Surgical Site Infections: A Call to Arms.
AB - Despite decades of attention and advances in medical treatments, surgical site
infections (SSI) remain a significant problem to our patients. Surprisingly, the
reported incidence of SSI has not changed appreciably in the past five decades,
although not surprisingly the timing to diagnosis (inpatient vs. outpatient) has
changed. Although the patient consequences have not escaped our notice, until
recently the costs associated with SSI have been difficult to ascertain. In this
review, we discuss the relevant history of SSI monitoring, the incidence as well
as the costs and consequences associated with this complication.
PMID- 28402729
TI - Differential Regulation of chTLR3 by Infectious Bursal Disease Viruses with
Different Virulence In Vitro and In Vivo.
AB - Toll-like receptor 3 (TLR3) is one of the TLRs whose ligand is double-stranded
RNA (dsRNA). Infectious bursal disease virus (IBDV) is a dsRNA virus that could
be recognized by TLR3. The purpose of this study was to determine the role of the
virulence of IBDV on the expression of chicken TLR3 (chTLR3). For this purpose,
the levels of chTLR3 expression and its downstream effectors, Interferon beta
(IFN-beta) and Interleukin 8 (IL-8), were detected and analyzed after infection
of IBDV field isolates with differential virulence in vitro (chicken embryo
fibroblast and/or chicken peripheral blood mononuclear cells) and in vivo
(commercial Three-Yellow chicken). The results showed that chTLR3 was activated
by IBDV, resulting in the expression of antiviral IFN-beta and chemokine IL-8.
The expression of chTLR3, IFN-beta, and IL-8 correlated well with the virulence
of IBDV as the more virulent the IBDV strain that was used, the more pronounced
was the expression of chTLR3, IFN-beta, and IL-8. These results suggest that
chTLR3 is involved in the pathogenesis of IBDV in commercial chickens and its
downstream effectors (IFN-beta and IL-8) might play an important role in this
process.
PMID- 28402730
TI - Light-emitting Diode Beam Profile and Spectral Output Influence on the Degree of
Conversion of Bulk Fill Composites.
AB - OBJECTIVES: To evaluate the beam profile and the spectral output of monowave and
polywave light-emitting diodes (LEDs) and their influence on the degree of
conversion (DC) of bulk fill composites. METHODS: A monowave LED (Smartlite
Focus, Dentsply) and a polywave LED (Valo Cordless, Ultradent) were characterized
using a resin calibrator and a laser beam profile analyzer. Two bulk fill
composites, Sonic Fill 2 (SF) containing camphorquinone (CQ) and Tetric EvoCeram
Bulk Fill (TEB) containing CQ associated with alternative photoinitiators, were
placed in custom-designed molds (n=3) and photoactivated by the monowave or
polywave LED with 20 J/cm2. To map the DC, longitudinal cross sections (0.5 mm
thick) from the center of the restoration were evaluated using FT-NIR microscopy.
SF and TEB light transmittances (n=3) through 4-mm-thick specimens were evaluated
during curing. Data were analyzed using a split-plot analysis of variance and
Tukey test (alpha=0.05; beta=0.2). RESULTS: The monowave LED had a radiant
emittance of 20 +/- 0.5 J/cm2 over 420-495 nm, and the polywave LED had an
emittance of 15.5 +/- 0.4 J/cm2 over 420-495 nm and of 4.5 +/- 0.2 J/cm2 over 380
420 nm. The total radiant exposure at the bottom of TEB was 2.2 +/- 0.2 J/cm2
with the monowave LED and 1.6 +/- 0.3 J/cm2 with the polywave LED, and for SF it
was 0.4 +/- 0.1 J/cm2 for both LEDs. There were no differences in the curing
profiles produced either by the monowave or the polywave LED (p=0.9), according
to the regions under influence of blue and/or violet emission at the same depth.
There was no statistical difference in the DC for SF using the monowave or
polywave LED at any depth (p=0.29). TEB had a higher DC at up to 2 mm in depth
when the polywave LED was used (p<0.004), but no differences were found when
starting at 2.5 mm. CONCLUSIONS: Monowave and polywave LEDs emitted
nonhomogeneous light beams, but this did not affect the DC homogeneity of bulk
fill composites. For composites containing CQ associated with alternative
photoinitiators, polywave LEDs had a higher DC, but only at the top part of the
restoration; lower wavelength absorption photoinitiators were ineffective in
deeper areas.
PMID- 28402731
TI - Characterization of Inorganic Filler Content, Mechanical Properties, and Light
Transmission of Bulk-fill Resin Composites.
AB - OBJECTIVES: The aims of this study were to characterize inorganic content (IC),
light transmission (LT), biaxial flexural strength (BFS), and flexural modulus
(FM) of one conventional (layered) and four bulk-fill composites at different
depths. METHODS: Bulk-fill composites tested were Surefil SDR flow (SDR), Filtek
Bulk Fill (FBF), Tetric EvoCeram Bulk Fill (TEC), and EverX Posterior (EXP).
Herculite Classic (HER) was used as a control. Energy dispersive x-ray analysis
and scanning electron microscopy were used to characterize filler particle
composition and morphology. The LT through different composite thicknesses (1, 2,
3, and 4 mm) was measured using a laboratory-grade spectral radiometer system
(n=5). For the BFS and FM tests, sets of eight stacked composite discs (0.5-mm
thick) were prepared simulating bulk filling of a 4-mm-thick increment (n=8).
RESULTS: SDR demonstrated larger, irregular particles than those observed in TEC
or HER. Filler particles in FBF were spherical, while those in EXP were composed
of fiberglass strands. The LT decreased with increased composite thickness for
all materials. Bulk-fill composites allowed higher LT than the HER. Furthermore,
HER proved to be the unique material, having lower BFS values at deeper regions.
SDR, FBF, and TEC bulk-fill composites presented reduced FM with increasing
composite depth. CONCLUSIONS: The bulk-fill composites investigated exhibited
higher LT, independent of different filler content and characteristics. Although
an increase in composite thickness reduced LT, the BFS of bulk-fill composites at
deeper layers was not compromised.
PMID- 28402732
TI - Different Methods for Inlay Production: Effect on Internal and Marginal
Adaptation, Adjustment Time, and Contact Point.
AB - The aim of this study was to evaluate the effect of different production methods
of resin and ceramic inlays on marginal and internal adaptation, adjustment time,
and proximal contacts. Forty premolars were selected, embedded (their roots), and
prepared to receive inlays that were made as follows (n=10): LaRe-digital
impression with a Lava C.O.S. scanner, followed by milling of Lava Ultimate block
(composite resin) in a milling center; CeRe-digital impression with a Cerec 3D
Bluecam scanner, followed by milling of Lava Ultimate block in Cerec; CeDis
digital impression with a Cerec 3D Bluecam scanner, followed by milling of IPS
e.max CAD block (lithium disilicate) in Cerec; and PresDis-impression with
polyvinyl siloxane, inlay made using the lost wax technique and IPS e.max Press
pressed ceramic (lithium disilicate). Marginal and internal adaptations were
measured using the replica technique. The inlay adjustments were performed using
diamond burs in a contra-angle hand piece, and the time for adjustment was
recorded using a timer, in seconds. The tightness of the proximal contact was
measured using standardized metal blades. The statistical analyses for marginal
fit data showed that at the cervical edge, CeDis (177.8 MUm) had greater misfit
than CeRe (116.7 MUm), while all the groups had similar adaptation at the
occlusal edge. The groups had similar internal fit at the pulpal wall, while LaRe
(104.7 MUm) > CeDis (66.7 MUm) = CeRe (76.7 MUm) at the axial wall. The groups
restored with lithium disilicate ceramic took more time for adjustment when
compared to the resin restorative material. The lowest proximal contact, in
micrometers, was seen in the CeRe group (8.8 MUm).
PMID- 28402733
TI - Effect of Surface Treatment, Silane, and Universal Adhesive on Microshear Bond
Strength of Nanofilled Composite Repairs.
AB - PURPOSE: The aim of this study was to evaluate the effect of surface treatment
and universal adhesive on the microshear bond strength of nanoparticle composite
repairs. METHODS: One hundred and forty-four specimens were built with a
nanofilled composite (Filtek Supreme Ultra, 3M ESPE). The surfaces of all the
specimens were polished with SiC paper and stored in distilled water at 37
degrees C for 14 days. Half of the specimens were then air abraded with Al2O3
particles and cleaned with phosphoric acid. Polished specimens (P) and polished
and air-abraded specimens (A), respectively, were randomly divided into two sets
of six groups (n=12) according to the following treatments: hydrophobic adhesive
only (PH and AH, respectively), silane and hydrophobic adhesive (PCH, ACH),
methacryloyloxydecyl dihydrogen phosphate (MDP)-containing silane and hydrophobic
adhesive (PMH, AMH), universal adhesive only (PU, AU), silane and universal
adhesive (PCU, ACU), and MDP-containing silane and universal adhesive (PMU, AMU).
A cylinder with the same composite resin (1.1-mm diameter) was bonded to the
treated surfaces to simulate the repair. After 48 hours, the specimens were
subjected to microshear testing in a universal testing machine. The failure area
was analyzed under an optical microscope at 50* magnification to identify the
failure type, and the data were analyzed by three-way analysis of variance and
the Games-Howell test (alpha=0.05). RESULTS: The variables "surface treatment"
and "adhesive" showed statistically significant differences for p<0.05. The
highest mean shear bond strength was found in the ACU group but was not
statistically different from the means for the other air-abraded groups except
AH. All the polished groups except PU showed statistically significant
differences compared with the air-abraded groups. The PU group had the highest
mean among the polished groups. Cohesive failure was the most frequent failure
mode in the air-abraded specimens, while mixed failure was the most common mode
in the polished specimens. CONCLUSIONS: While air abrasion with Al2O3 particles
increased the repair bond strength of the nanoparticle composite, the use of MDP
containing silane did not lead to a statistically significant increase in bond
strength. Silane-containing universal adhesive on its own was as effective as any
combination of silane and adhesive, particularly when applied on air-abraded
surfaces.
PMID- 28402734
TI - Masking Colored Substrates Using Monolithic and Bilayer CAD-CAM Ceramic
Structures.
AB - OBJECTIVE: To evaluate the masking ability and translucency of monolithic and
bilayer CAD-CAM ceramic structures. METHODS: Discs of high translucency (HT) and
low translucency (LT) lithium disilicate-based ceramic (IPS e.max CAD) with
different thicknesses (0.7, 1, 1.5, and 2 mm) were evaluated as a monolithic
structure or combined (bilayer) with a 0.5-mm-thick zirconia framework (IPS e.max
ZirCAD). The masking ability and translucency were calculated based on CIE L*a*b*
color coordinates measured with a spectrophotometer (SP60, X-Rite). The
translucency parameter (TP) was calculated using color coordinates measured over
standard white-and-black backgrounds. The masking ability was calculated by
CIEDE2000 color difference metric (DeltaE00) for each specimen measured over a
tooth-colored substrate (shade A2) compared to three darker backgrounds (shade C4
and two metal substrates). Confidence intervals (CI) for the means (95% CI) were
calculated for TP and DeltaE00. The Pearson correlation between DeltaE00 and TP
was investigated for monolithic and bilayer structures over all backgrounds.
RESULTS: The thinner the lithium disilicate layer, the greater the translucency
and the higher the DeltaE00 values. The effect of ceramic thickness on both
translucency and masking ability was more pronounced for the monolithic
structures. In addition, monolayers always presented a greater color variation
than their bilayer counterparts. The metallic background produced greater
DeltaE00 than the C4-shaded substrate. CONCLUSION: Monolithic veneers were able
to mask C4-shaded background but did not mask metallic backgrounds. Bilayer
structures showed greater shade masking ability than monolithic structures.
PMID- 28402735
TI - Microhardness and Roughness of Infiltrated White Spot Lesions Submitted to
Different Challenges.
AB - A white spot lesion is the first clinical sign of a caries lesion and represents
mineral loss from the enamel subsurface. The purpose of this study was to
evaluate the microhardness and surface roughness of white spot lesions after
application of a resin infiltrant and subjection to different challenges. Caries
like lesions were induced in bovine enamel discs (n=50), and the specimens were
randomly divided into five study groups (n=10): demineralized enamel (negative
control, G1), infiltrated enamel (G2), infiltrated enamel submitted to brushing
(G3), infiltrated enamel submitted to pH cycling (G4), and infiltrated enamel
submitted to artificial aging (G5). Half of each enamel surface was used as its
own positive control. Roughness data were analyzed using the Kruskal-Wallis test
followed by the Dunn test. Results from microhardness were analyzed by two-way
analysis of variance, followed by the Tukey test for multiple comparisons. The
level of significance was set at 5%. Microhardness and roughness values obtained
from the test side of the specimens were significantly lower compared with the
sound enamel for all groups. Microhardness values obtained for G2, G3, and G5
were not significantly different. Values found for G1 were significantly lower
compared with those for G2, G3, and G5. The lowest microhardness values were
observed for G4, which was significantly different from the other groups. Surface
roughness was not significantly different between G2 and G3. The resin infiltrant
presented superiority over the unprotected white spot lesions, as they were more
resistant to mechanical and aging challenges. However, resin infiltration was not
able to reestablish the properties of sound enamel and was not resistant to a new
cariogenic challenge.
PMID- 28402736
TI - Characterization of a Diamond Ground Y-TZP and Reversion of the Tetragonal to
Monoclinic Transformation.
AB - PURPOSE: To characterize the surface of an yttria-stabilized zirconia (Y-TZP)
ceramic after diamond grinding in terms of its crystalline phase, morphology,
mean roughness (Ra), and wettability as well as to determine a thermal treatment
to reverse the resulting tetragonal to monoclinic (t-m) transformation. METHODS
AND MATERIALS: Y-TZP specimens were distributed into different groups according
to the actions (or no action) of grinding and irrigation. Grinding was
accomplished using a diamond stone at a low speed. The samples were characterized
by x-ray diffraction (XRD), scanning electron microscopy, goniometry, and
profilometry. In situ high-temperature XRD was used to determine an annealing
temperature to reverse the t-m transformation. Ra was submitted to the Kruskal
Wallis test, followed by the Dunn test (alpha=0.05). The volume fraction of the
monoclinic phase and contact angle were submitted to one-way analysis of
variance, followed by the Tukey test (alpha=0.05). RESULTS: Monoclinic zirconia
was observed on the surface of samples after dry and wet grinding with a diamond
stone. The volume fraction of the monoclinic phase was smaller on the dry ground
samples (3.6%+/-0.3%) than on the wet ground samples (5.6%+/-0.3%). High
temperature XRD showed reversion of the t-m phase transformation, which started
at 700 degrees C and completed at 800 degrees C in a conventional oven.
CONCLUSIONS: Grinding with a diamond stone partially transformed the crystalline
phase on the surface of a Y-TZP ceramic from tetragonal to monoclinic zirconia
while simultaneously increasing the surface roughness and wettability. The t-m
transformation could be reversed by heat treatment at 800 degrees C or 900
degrees C for 60 minutes or 1000 degrees C for 30 minutes.
PMID- 28402737
TI - Comparison of Polymerization Shrinkage, Physical Properties, and Marginal
Adaptation of Flowable and Restorative Bulk Fill Resin-Based Composites.
AB - PURPOSE: The purpose of this study was to compare the marginal adaptation of two
flowable bulk fill resin-based composites (FB-RBCs), two restorative bulk fill
resin-based composites (RB-RBCs), and one regular incremental-fill RBC in MOD
cavities in vitro. Additionally, the influence of linear polymerization
shrinkage, shrinkage force, flexural modulus, and bottom/top surface hardness
ratio on the marginal adaptation was evaluated. METHODS: A Class II MOD cavity
was prepared in 40 extracted sound lower molars. In group 1 (control group), the
preparation was filled with Filtek Z350 (Z3, 3M ESPE, St Paul, MN, USA) using the
incremental filling technique. The FB-RBCs, SDR (SD, group 2) (Dentsply Caulk,
Milford, DE, USA) and Venus Bulk Fill (VB, group 3) (Heraeus Kulzer, Dormagen,
Germany), were placed in the core portion of the cavity first, and Z350 was
filled in the remaining cavity. The RB-RBCs, Tetric N-Ceram Bulkfill (TB, group
4) (Ivoclar Vivadent, Schaan, Liechtenstein) and SonicFill (SF, Group 5) (Kerr,
West Collins, Orange, CA, USA), were bulk filled into the preparation. Images of
the magnified marginal area were captured under 100* magnification before and
after thermomechanical loading, and the percentage ratio of the imperfect margin
(%IMwhole) was calculated. Gaps, cracks in the enamel layer, and chipping of
composite, enamel, or dentin were all considered to be imperfect margins. Linear
polymerization shrinkage, polymerization shrinkage force, flexural strength,
flexural modulus, and bottom/top surface hardness ratio of were measured. Eight
specimens were allocated for each material for each test. One-way analysis of
variance with the Scheffe test was used to compare the groups at a 95% confidence
level. RESULTS: Before thermomechanical loading, %IMwhole was in the order of
group 3 <= groups 2 and 5 <= groups 1 and 4 (p=0.011), whereas after loading, it
was in the order of group 4 <= group 5 <= group 1 <= groups 2 and 3 (p<0.001).
The order of materials were Z3 < TB and SF < SD and VB (p<0.001) in
polymerization shrinkage; SF <= TB <= Z3 < SD < VB (p<0.001) in polymerization
shrinkage force; VB < SD < TB <= Z3 <= SF (p<0.001) in flexural modulus; SD, VB,
and TB < Z3 and SF (p<0.001) in flexural strtength; and SF< Z3 < TB < VB and SD
(p<0.001) in bottom/top surface hardness ratio. The Pearson correlation constant
between %IMwhole and polymerization shrinkage, shrinkage force, elastic modulus,
and bottom/top surface hardness ratio was 0.697, 0.708, -0.373, and 0.353,
respectively, after thermomechanical loading. CONCLUSION: Within the limitations
of this study, RB-RBCs showed better marginal adaptation than FB- RBCs. The lower
level of polymerization shrinkage and polymerization shrinkage stress in RB-RBCs
seems to contribute to this finding because it would induce less polymerization
shrinkage force at the margin. FB-RBCs with lower flexural modulus may not
provide an effective buffer to occlusal stress when they are capped with regular
RBCs.
PMID- 28402738
TI - Ferrule-Effect Dominates Over Use of a Fiber Post When Restoring Endodontically
Treated Incisors: An In Vitro Study.
AB - OBJECTIVES: The aim of this study was to investigate the restoration of broken
down endodontically treated incisors with the ferrule effect using glass ceramic
crowns bonded to composite resin core buildups with or without a fiber post. A no
ferrule group with post was also included for comparison. METHODS AND MATERIALS:
Thirty decoronated endodontically treated bovine incisors with a 2-mm ferrule
were restored with a direct buildup using a nanohybrid direct composite resin
(Miris 2 and Optibond FL) with or without a glass-fiber-reinforced post. An
additional group of 15 teeth without a ferrule were restored with buildup and a
fiber post. All teeth were prepared to receive bonded glass ceramic crowns (e.max
CAD luted with Variolink Esthetic DC) and were subjected to accelerated fatigue
testing. Cyclic isometric loading was applied to the incisal edge at an angle of
30 degrees and a frequency of 5 Hz, beginning with a load of 100 N (*5000
cycles). A 100 N load increase was applied each 15,000 cycles. Specimens were
loaded until failure or to a maximum of 1000 N (*140,000 cycles). Groups were
compared using the Kaplan Meier survival analysis (log rank test at p=0.05).
RESULTS: None of the tested specimens withstood all 140,000 load cycles.
Specimens with posts but without a ferrule were affected by an initial failure
phenomenon (wide gap at the lingual margin between the buildup/crown assembly and
the root). There was a significant difference in mean survived cycles between the
ferrule groups (Fp=73,332* and FNp=73,244*) and the no-ferrule group (50,121*;
p=0.001). The addition of a fiber post was not significant in the presence of the
ferrule (p=0.884). In both groups with posts, 100% of failures were unrestorable.
The no-post group had 47% of restorable and possibly restorable failures.
CONCLUSIONS: The survival of broken-down nonvital incisors was improved by the
presence of the ferrule but not by the fiber-reinforced post. Fiber posts were
always detrimental to the failure mode and were not able to compensate for the
absence of a ferrule.
PMID- 28402739
TI - Remembering Judith Bradford and Why Populations Matter.
PMID- 28402740
TI - Patients at High-Risk for Surgical Site Infection.
AB - BACKGROUND: Surgical site infections (SSIs) are a significant healthcare quality
issue, resulting in increased morbidity, disability, length of stay, resource
utilization, and costs. Identification of high-risk patients may improve pre
operative counseling, inform resource utilization, and allow modifications in
peri-operative management to optimize outcomes. METHODS: Review of the pertinent
English-language literature. RESULTS: High-risk surgical patients may be
identified on the basis of individual risk factors or combinations of factors. In
particular, statistical models and risk calculators may be useful in predicting
infectious risks, both in general and for SSIs. These models differ in the number
of variables; inclusion of pre-operative, intra-operative, or post-operative
variables; ease of calculation; and specificity for particular procedures.
Furthermore, the models differ in their accuracy in stratifying risk. Biomarkers
may be a promising way to identify patients at high risk of infectious
complications. CONCLUSIONS: Although multiple strategies exist for identifying
surgical patients at high risk for SSIs, no one strategy is superior for all
patients. Further efforts are necessary to determine if risk stratification in
combination with risk modification can reduce SSIs in these patient populations.
PMID- 28402742
TI - Vertebrate Ticks Distribution and Their Role as Vectors in Relation to Road Edges
and Underpasses.
AB - Roads fragment vertebrate populations and affect the dynamics and dispersal
patterns of vertebrate parasites. We evaluated how vertebrate ticks distribute
near roads and road underpasses in human-caused road-fragmented landscapes in
Seville, SW Spain. We sampled 49 stations with 93 individualized sampling points
and assessed tick abundance. We explored the relationship between tick presence
and abundance and distance to the nearest road and underpass (drainage culverts
and other passages used by vertebrates), and landscape features through
categorical regression and nonparametric statistics. The presence of the tick
borne pathogens Borrelia sp. and Bartonella sp. was also analyzed by PCR. We
found preliminary evidence of high relative tick abundance next to roads and in
the vicinity of road underpasses. Plant cover type was related to tick presence
in this road context. Implications of road permeability and edge effect in
patterns of vertebrate-tick relationships in road fragmentation contexts are
discussed. Both Borrelia sp. and Bartonella sp. were detected in the ticks
analyzed. This is the first report of these bacteria in ticks from Seville. The
results confirm the potential risk of acquiring Lyme disease and bartonellosis in
this area.
PMID- 28402743
TI - Generation and Application of Monoclonal Antibody Against Lycopene.
AB - A monoclonal antibody (Mab) against lycopene was developed from hybridoma clones
obtained from BALB/c mice immunized with trans-isomer of lycopene (t-lycopene, t
LC) conjugated with colloidal gold particles. An alternating immunization
schedule which included injection of both formulations of immunogen (without and
with Freund's adjuvant) was most effective in the elucidation of a measurable
immune response to the t-Lycopene conjugate. Selected hybridoma clones were able
to produce an Mab positive in competition assay. In particular, preincubation of
6B9 Mabs with t-LC abolished the ability of 6B9 Mabs to bind LC in the
competition assay. Mabs produced by other clones (4F10, 4A3, and 3B12) worked
similarly. Analysis of antigen specificity showed that 6B9 Mab raised against t
LC did not recognize other carotenoids such as lutein and carotene. Mab 6B9 was
shown to recognize lycopene on a glass surface and in the settings of indirect
immunofluorescence experiments performed in cultured hepatocytes and alveolar
macrophages incubated with and without lycopene, as well as in sebum and
corneocyte specimens from the skin of volunteers supplemented with nutraceutical
formulation of lycopene. Newly generated Mabs against lycopene may provide a
valuable tool for different analytical assays of lycopene content in various
biological, agricultural, and food products.
PMID- 28402744
TI - Single-Incision Versus Three-Port Laparoscopic Appendectomy: Short- and Long-Term
Outcomes.
AB - AIM: To compare the outcome of patients who had undergone single-incision
laparoscopic appendectomy (SILA) with others who had undergone three-port
laparoscopic appendectomy (3-PORT). MATERIALS AND METHODS: Data from all adults
with uncomplicated appendicitis treated by laparoscopic appendectomy between June
2012 and December 2015 were prospectively collected. Patients with chronic pain,
appendix malignancy, at least two previous laparotomies, and those undergoing
concomitant surgery for different condition were excluded from analysis.
Postoperative pain was assessed by a visual analog scale (VAS). Patients were
reviewed postoperatively at 7 days and 1 month in the outpatient clinic. Late
complications were assessed with a telephonic interview. RESULTS: A total of 91
patients were included (46 SILA; 45 3-PORT). There were 16 males and 30 females
in the SILA group (mean age = 26.76 +/- 10.58 years) and 18 males and 27 females
in the 3-PORT group (mean age = 26.84 +/- 10.79 years). The mean operative time
for SILA was 48.54 +/- 12.80 min, for the 3-PORT group the mean operative time
was 46.33 +/- 15.54 min (P = 0.46). No case required conversion. Mean
postoperative hospital length of stay was 1.87 +/- 0.69 days for SILA and 2.38 +/
1.11 days for 3-PORT (P = 0.01). VAS value of 3.91 +/- 1.96 and mean ketorolac
usage of 0.38 +/- 0.65 in 3-PORT group and SILA patients reported 3.70 +/- 1.58
and 0.39 +/- 0.58, respectively (P = 0.91). Our mean follow-up in SILA group was
25.75 +/- 10.82 months, for 3-PORT group the mean follow-up was 26.9 +/- 11.8
months. Eleven patients missed long-term follow-up. No incisional hernia was
found. There is a statistically significant difference in cosmetic evaluation in
favor of SILA (P < 0.005). CONCLUSIONS: There was no difference in operative
time, early complications, postoperative pain, analgesia requirement between SILA
and 3-PORT laparoscopic appendectomy, but after SILA procedure discharge was
quicker and long-term cosmetic satisfaction was superior.
PMID- 28402746
TI - Single-Incision, Gasless, Endoscopic Trans-Axillary Total Thyroidectomy: A
Feasible and Oncologic Safe Surgery in Patients with Papillary Thyroid Carcinoma.
AB - BACKGROUND: The aim of this study is to compare the feasibility and oncologic
safety of Single-incision, gasless, Endoscopic trans-axillary bilateral Total
thyroidectomy (SET) with open cervical total thyroidectomy in patients with
papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: From March 2008 to
December 2012, PTC patients underwent bilateral total thyroidectomy.
Conventional, open surgery was performed on 538 patients (Group O) and endoscopic
surgery was performed on 200 patients (Group E). We analyzed the patient's
clinicopathologic, postoperative complications, and surgical completeness.
RESULTS: The mean ages of the patients were 48.9 +/- 0.5 (range = 24-77) in Group
O and 39.5 +/- 0.8 (range = 17-73) in Group E with statistical significance (P <
.001). Percentage of female patients were 74.3% in Group O and 96.0% in Group E
with statistical significance (P < .001). The postoperative hospital stay in
Group O was significantly longer than Group E (4.60 +/- 0.05 versus 3.30 +/-
0.05; P < .001). The operation time in Group E was significantly longer than
Group O (93.9 +/- 1.3 versus 142.6 +/- 3.3; P < .001). More transient
hypocalcemia was found in Group O compared to Group E with statistical
significance (28.1% versus 22.4%; P < .001). There were no significant
differences with respect to permanent hypocalcemia, permanent recurrent laryngeal
nerve palsy, seroma, and hematoma. The mean 1 year-stimulated sTg was 0.23 +/-
0.03 and 0.18 +/- 0.02 in Group O and E, respectively. Tumor recurrence during
short-term follow-up at neck ultrasonography (1 year) was detected in 4 patients
in Group O. CONCLUSION: SET is safe and effective, not only for low-risk patients
with early-detected cancer, but also for selected cases of advanced cancer.
PMID- 28402745
TI - Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure.
AB - BACKGROUND: In patients with acute heart failure, early intervention with an
intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac
wall stress and, potentially, myocardial injury, thereby favorably affecting
patients' long-term prognosis. METHODS: In this double-blind trial, we randomly
assigned 2157 patients with acute heart failure to receive a continuous
intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body
weight per minute or matching placebo for 48 hours, in addition to accepted
therapy. Treatment was initiated a median of 6 hours after the initial clinical
evaluation. The coprimary outcomes were death from cardiovascular causes during a
median follow-up of 15 months and a hierarchical composite end point that
evaluated the initial 48-hour clinical course. RESULTS: Death from cardiovascular
causes occurred in 236 patients in the ularitide group and 225 patients in the
placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85
to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant
between-group difference with respect to the hierarchical composite outcome. The
ularitide group had greater reductions in systolic blood pressure and in levels
of N-terminal pro-brain natriuretic peptide than the placebo group. However,
changes in cardiac troponin T levels during the infusion did not differ between
the two groups in the 55% of patients with paired data. CONCLUSIONS: In patients
with acute heart failure, ularitide exerted favorable physiological effects
(without affecting cardiac troponin levels), but short-term treatment did not
affect a clinical composite end point or reduce long-term cardiovascular
mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number,
NCT01661634 .).
PMID- 28402747
TI - Randomized Phase II Study Investigating Pazopanib Versus Weekly Paclitaxel in
Relapsed or Progressive Urothelial Cancer.
AB - Purpose Two previous single-arm trials have drawn conflicting conclusions
regarding the activity of pazopanib in urothelial cancers after failure of
platinum-based chemotherapy. Patients and Methods This randomized (1:1) open
label phase II trial compared the efficacy of pazopanib 800 mg orally with
paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in the second-line setting.
The primary end point was overall survival (OS). Results Between August 2012 and
October 2014, 131 patients, out of 140 planned, were randomly assigned. The study
was terminated early on the recommendation of the independent data monitoring
committee because of futility. Final analysis after the preplanned number of
deaths (n = 110) occurred after a median follow-up of 18 months. One hundred
fifteen deaths had occurred at the final data extract presented here. Median OS
was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for
pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for
baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P =
.89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0
to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09;
80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred
in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. Conclusion
Pazopanib did not have greater efficacy than paclitaxel in the second-line
treatment of urothelial cancers. There was a trend toward superior OS for
paclitaxel.
PMID- 28402749
TI - Mental Health Concerns and Insurance Denials Among Transgender Adolescents.
AB - PURPOSE: Transgender youth are at high risk for mental health morbidities. Based
on treatment guidelines, puberty blockers and gender-affirming hormone therapy
should be considered to alleviate distress due to discordance between an
individual's assigned sex and gender identity. The goals of this study were to
examine the: (1) prevalence of mental health diagnoses, self-injurious behaviors,
and school victimization and (2) rates of insurance coverage for hormone therapy,
among a cohort of transgender adolescents at a large pediatric gender program, to
understand access to recommended therapy. METHODS: An IRB-approved retrospective
medical record review (2014-2016) was conducted of patients with ICD 9/10 codes
for gender dysphoria referred to pediatric endocrinology within a large
multidisciplinary gender program. Researchers extracted the following details:
demographics, age, assigned sex, identified gender, insurance provider/coverage,
mental health diagnoses, self-injurious behavior, and school victimization.
RESULTS: Seventy-nine records (51 transgender males, 28 transgender females) met
inclusion criteria (median age: 15 years, range: 9-18). Seventy-three subjects
(92.4%) were diagnosed with one or more of the following conditions: depression,
anxiety, post-traumatic stress disorder, eating disorders, autism spectrum
disorder, and bipolar disorder. Fifty-nine (74.7%) reported suicidal ideation, 44
(55.7%) exhibited self-harm, and 24 (30.4%) had one or more suicide attempts.
Forty-six (58.2%) subjects reported school victimization. Of the 27 patients
prescribed gonadotropin-releasing hormone analogues, only 8 (29.6%) received
insurance coverage. CONCLUSION: Transgender youth face significant barriers in
accessing appropriate hormone therapy. Given the high rates of mental health
concerns, self-injurious behavior, and school victimization among this vulnerable
population, healthcare professionals must work alongside policy makers toward
insurance coverage reform.
PMID- 28402748
TI - Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for
Early-Stage Breast Cancer.
AB - Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing
use of multiple-gene panels that can yield uncertain results. However, little is
known about the context of such testing or its impact on treatment. Methods A
population-based sample of patients with breast cancer diagnosed in 2014 to 2015
and identified by two SEER registries (Georgia and Los Angeles) were surveyed
about genetic testing experiences (N = 3,672; response rate, 68%). Responses were
merged with SEER data. A patient subgroup at higher pretest risk of pathogenic
mutation carriage was defined according to genetic testing guidelines. Patients'
attending surgeons were surveyed about genetic testing and results management. We
examined patterns and correlates of genetic counseling and testing and the impact
of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six
patients reported genetic testing. Although two thirds of patients were tested
before surgical treatment, patients without private insurance more often
experienced delays. Approximately half of patients (57% at higher pretest risk,
42% at average risk) discussed results with a genetic counselor. Patients with
pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM
(higher risk, 80%; average risk, 85%); however, BLM was also common among
patients with genetic variants of uncertain significance (VUS; higher risk, 43%;
average risk, 51%). Surgeons' confidence in discussing testing increased with
volume of patients with breast cancer, but many surgeons (higher volume, 24%;
lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with
BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are
tested without ever seeing a genetic counselor. Half of average-risk patients
with VUS undergo BLM, suggesting a limited understanding of results that some
surgeons share. These findings emphasize the need to address challenges in
personalized communication about genetic testing.
PMID- 28402750
TI - An Efficient Nurse Practitioner-Led Community-Based Service Model for Delivering
Coordinated Care to Persons With Serious Mental Illness at Risk for Homelessness
[Formula: see text].
AB - BACKGROUND: Access to mental health care is a struggle for those with serious
mental illness (SMI). About 25% of homeless suffer from SMI, compared with 4.2%
of the general population. OBJECTIVE: From 2003 to 2012, St. Paul's Center (SPC)
operated a unique model to provide quality care to the homeless and those at risk
for homelessness, incarceration, and unnecessary hospitalization because of SMI.
Data were available for analysis for the years 2008 to 2010. DESIGN: The SPC was
developed, managed, and staffed by board-certified psychiatric/mental health
nurse practitioners, offering comprehensive mental health services and
coordinated interventions. RESULTS: All clients were housed and none
incarcerated. From 2008 to 2010, only 3% of clients were hospitalized, compared
with 7.5% of adults with SMI. Clinical, academic, and community partnerships
increased value, but Medicaid reimbursement was not available. CONCLUSION: Mental
health provisions in the recently passed 21st Century Cures Act support community
mental health specialty treatment. The SPC provides a template for similar nurse
practitioner-led models.
PMID- 28402751
TI - Economic Disparities and Syphilis Incidence in Massachusetts, 2001-2013.
AB - OBJECTIVES: We used area-level indicators of poverty to describe economic
disparities in the incidence rate of infectious syphilis in Massachusetts to (1)
determine whether methods developed in earlier AIDS analyses in Massachusetts
could be applied to syphilis and (2) characterize syphilis trends during a time
of increased rates of syphilis incidence. METHODS: Using census tract data and
population counts from the US Census Bureau and Massachusetts data on syphilis,
we analyzed the incidence rate of syphilis infection from 2001 to 2013 by the
poverty level of the census tract in which people with syphilis resided,
stratified by age, sex, and race/ethnicity. RESULTS: The syphilis incidence rate
increased in all census tract groups in Massachusetts from 2001 to 2013, and
disparities in incidence rates by area poverty level persisted over time. The
overall incidence rate of syphilis increased 6.9-fold from 2001 to 2013 in all
census tract poverty-level groupings (from 1.5 to 10.3 per 100 000 population),
but the rise in rate was especially high in the poorest census tracts (from 5.6
to 31.0 per 100 000 population) and among men (from 2.2 to 19.4 per 100 000
population). The highest syphilis incidence rate was among non-Hispanic black
people. The largest changes in incidence rate occurred after 2010. One region had
a disproportionate increase in incidence rates and a disproportionate impact on
the statewide trend. CONCLUSIONS: Census tract poverty analyses can inform the
targeting of interventions that make progress toward reducing disparities in
rates of syphilis incidence possible.
PMID- 28402753
TI - Author's response: smoking cessation treatment in substance use disorder
settings.
PMID- 28402752
TI - The MicroRNA miR-210 Is Expressed by Cancer Cells but Also by the Tumor
Microenvironment in Triple-Negative Breast Cancer.
AB - The triple-negative breast cancer (TNBC) subtype occurs in about 15% of breast
cancer and is an aggressive subtype of breast cancer with poor outcome.
Furthermore, treatment of patients with TNBC is more challenging due to the
heterogeneity of the disease and the absence of well-defined molecular targets.
Microribonucleic acid (RNA) represents a new class of biomarkers that are
frequently dysregulated in cancer. It has been described that the microRNA miR
210 is highly expressed in TNBC, and its overexpression had been linked to poor
prognosis. TNBC are often infiltrated by immune cells that play a key role in
cancer progression. The techniques traditionally used to analyze miR-210
expression such as next generation sequencing or quantitative real-time
polymerase chain reaction (PCR) do not allow the precise identification of the
cellular subtype expressing the microRNA. In this study, we have analyzed miR-210
expression by in situ hybridization in TNBC. The miR-210 signal was detected in
tumor cells, but also in the tumor microenvironment, in a region positive for the
pan-leucocyte marker CD45-LCA. Taken together, our results demonstrate that miR
210 is expressed in tumor cells but also in the tumor microenvironment. Our
results also highlight the utility of using complementary approaches to take into
account the cellular context of microRNA expression.
PMID- 28402754
TI - Disease Modification in Acute Decompensated Heart Failure.
PMID- 28402755
TI - Distribution of FcRn Across Species and Tissues.
AB - The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I
type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and
albumin, thereby protecting them from lysosomal degradation. Therefore, besides
the knowledge of FcRn affinity, FcRn protein expression is critical in
understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such
as monoclonal antibodies. The goal of this investigation was to achieve for the
first time a comparative assessment of FcRn distribution across a variety of
tissues and species. FcRn was mapped in about 20 tissues including placenta from
human and the most frequently used species in non-clinical safety testing of
monoclonal antibodies (mouse, rat, cynomolgus monkey). In addition, the FcRn
expression pattern was characterized in two humanized transgenic mouse lines
(Tg32 and Tg276) expressing human FcRn under different promoters, and in the
severe combined immunodeficient (SCID) mouse. Consecutive sections were stained
with specific markers, namely, anti-CD68 for macrophages and anti-von Willebrand
Factor for endothelial cells. Overall, the FcRn expression pattern was comparable
across species and tissues with consistent expression of FcRn in endothelial
cells and interstitial macrophages, Kupffer cells, alveolar macrophages,
enterocytes, and choroid plexus epithelium. The human FcRn transgenic mouse Tg276
showed a different and much more widespread staining pattern of FcRn. In
addition, immunodeficiency and lack of IgG in SCID mice had no negative effect on
FcRn expression compared with wild-type mice.
PMID- 28402756
TI - Effectiveness of Manual Therapy and Stretching for Baseball Players With Shoulder
Range of Motion Deficits.
AB - BACKGROUND: Baseball players displaying deficits in shoulder range of motion
(ROM) are at increased risk of arm injury. Currently, there is a lack of
consensus regarding the best available treatment options to restore shoulder ROM.
HYPOTHESIS: Instrumented manual therapy with self-stretching will result in
clinically significant deficit reductions when compared with self-stretching
alone. STUDY DESIGN: Controlled laboratory study. METHODS: Shoulder ROM and
humeral torsion were assessed in 60 active baseball players (mean age, 19 +/- 2
years) with ROM deficits (nondominant - dominant, >=15 degrees ). Athletes were
randomly assigned to receive a single treatment of instrumented manual therapy
plus self-stretching (n = 30) or self-stretching only (n = 30). Deficits in
internal rotation, horizontal adduction, and total arc of motion were compared
between groups immediately before and after a single treatment session. Treatment
effectiveness was determined by mean comparison data, and a number-needed-to
treat (NNT) analysis was used for assessing the presence of ROM risk factors.
RESULTS: Prior to intervention, players displayed significant ( P < 0.001)
dominant-sided deficits in internal rotation (-26 degrees ), total arc of motion
(-18 degrees ), and horizontal adduction (-17 degrees ). After the intervention,
both groups displayed significant improvements in ROM, with the instrumented
manual therapy plus self-stretching group displaying greater increases in
internal rotation (+5 degrees , P = 0.010), total arc of motion (+6 degrees , P =
0.010), and horizontal adduction (+7 degrees , P = 0.004) compared with self
stretching alone. For horizontal adduction deficits, the added use of
instrumented manual therapy with self-stretching decreased the NNT to 2.2 (95%
CI, 2.1-2.4; P = 0.010). CONCLUSION: Instrumented manual therapy with self
stretching significantly reduces ROM risk factors in baseball players with motion
deficits when compared with stretching alone. CLINICAL RELEVANCE: The added
benefits of manual therapy may help to reduce ROM deficits in clinical scenarios
where stretching alone is ineffective.
PMID- 28402757
TI - Partners in Public Health: Public Health Collaborations With Schools of Pharmacy,
2015.
AB - To collect data on public health collaborations with schools of pharmacy, we sent
a short electronic survey to accredited and preaccredited pharmacy programs in
2015. We categorized public health collaborations as working or partnering with
local and/or state public health departments, local and/or state public health
organizations, academic schools or programs of public health, and other public
health collaborations. Of 134 schools, 65 responded (49% response rate). Forty
six (71%) responding institutions indicated collaborations with local and/or
state public health departments, 34 (52%) with schools or programs of public
health, and 24 (37%) with local and/or state public health organizations. Common
themes of collaborations included educational programs, community outreach,
research, and teaching in areas such as tobacco control, emergency preparedness,
chronic disease, drug abuse, immunizations, and medication therapy management.
Interdisciplinary public health collaborations with schools of pharmacy provide
additional resources for ensuring the health of communities and expose student
pharmacists to opportunities to use their training and abilities to affect public
health. Examples of these partnerships may stimulate additional ideas for
possible collaborations between public health organizations and schools of
pharmacy.
PMID- 28402758
TI - The Graft Bending Angle Can Affect Early Graft Healing After Anterior Cruciate
Ligament Reconstruction: In Vivo Analysis With 2 Years' Follow-up.
AB - BACKGROUND: A high graft bending angle (GBA) after anterior cruciate ligament
(ACL) reconstruction has been suggested to cause stress on the graft.
Nevertheless, evidence about its effect on graft healing in vivo is limited.
HYPOTHESIS: The signal intensity on magnetic resonance imaging (MRI) would be
higher in the proximal region of the ACL graft, and higher signals would be
correlated to a higher GBA. STUDY DESIGN: Descriptive laboratory study. METHODS:
Anatomic single-bundle ACL reconstruction was performed on 24 patients (mean age,
20 +/- 4 years) using the transportal technique. A quadriceps tendon autograft
with a bone plug was harvested. To evaluate graft healing, the signal/noise
quotient (SNQ) was measured in 3 regions of interest (ROIs) of the proximal,
midsubstance, and distal ACL graft using high-resolution MRI (0.45 * 0.45 * 0.70
mm), with decreased signals suggesting improved healing. Dynamic knee motion was
examined during treadmill walking and running to assess the in vivo GBA. The GBA
was calculated from the 3-dimensional angle between the graft and femoral tunnel
vectors at each motion frame, based on tibiofemoral kinematics determined from
dynamic stereo X-ray analysis. Graft healing and GBAs were assessed at 6 and 24
months postoperatively. Repeated-measures analysis of variance was used to
compare the SNQ in the 3 ROIs at 2 time points. Pearson correlations were used to
analyze the relationship between the SNQ and mean GBA during 0% to 15% of the
gait cycle. RESULTS: The SNQ of the ACL graft in the proximal region was
significantly higher than in the midsubstance ( P = .022) and distal regions ( P
< .001) at 6 months. The SNQ in the proximal region was highly correlated with
the GBA during standing ( R = 0.64, P < .001), walking ( R = 0.65, P = .002), and
running ( R = 0.54, P = .015) but not in the other regions. At 24 months, signals
in the proximal and midsubstance regions decreased significantly compared with 6
months ( P < .001 and P = .008, respectively), with no difference across the
graft area. CONCLUSION: The signal intensity was highest in the proximal region
and lowest in the distal region of the reconstructed graft at 6 months
postoperatively. A steep GBA was significantly correlated with high signal
intensities of the proximal graft in this early period. A steep GBA may
negatively affect proximal graft healing after ACL reconstruction.
PMID- 28402759
TI - Medial Posterior Capsular Plication Reduces Anterior Shoulder Instability Similar
to Remplissage Without Restricting Motion in the Setting of an Engaging Hill
Sachs Defect.
AB - BACKGROUND: Numerous surgical options for the management of engaging Hill-Sachs
lesions exist, of which remplissage has emerged as one of the most popular
arthroscopic techniques. Remplissage is not without disadvantages, however, and
has been demonstrated to potentially result in a loss of external rotation (ER)
due to nonanatomic tethering of the infraspinatus tendon and a potential decrease
in infraspinatus strength clinically. PURPOSE: The efficacy of posterior medial
capsular plication in addition to Bankart repair was examined as an arthroscopic
management strategy for an engaging Hill-Sachs defect. STUDY DESIGN: Controlled
laboratory study. METHODS: Eight fresh-frozen human cadaveric shoulders were
utilized for the study. After testing baseline translation and motion, 30% Hill
Sachs lesions were created in each specimen. Three experimental groups were
assembled: (1) isolated Bankart repair (HSD), (2) Bankart repair with remplissage
(RM), and (3) Bankart repair with posterior medial capsular plication (PL).
Biomechanical testing was performed to determine anterior translation, range of
motion, and Hill-Sachs engagement. Translation and motion measurements were
normalized to the baseline laxity values for each specimen. RESULTS: A
significant reduction in anterior translation was noted at 60 degrees of
abduction and 60 degrees of ER for both the PL and RM groups compared with the
HSD group throughout most of the joint loads tested ( P < .05), but no
significant differences were noted between the PL and RM groups at any load. The
RM group had significantly less normalized ER at 60 degrees of abduction
compared with the HSD and PL groups ( P < .05). There were no differences in
internal rotation between the groups. All 8 specimens in the HSD group engaged,
while no specimens in the RM and PL groups engaged ( P < .001). CONCLUSION: In a
cadaveric model, medial posterior capsular plication as an adjunct to Bankart
repair offers similar resistance to anterior translation and Hill-Sachs
engagement as compared with remplissage in the setting of an engaging Hill-Sachs
defect. Medial posterior capsular plication results in less restriction of ER
compared with remplissage without any significant limitation of internal
rotation. CLINICAL RELEVANCE: Posterior medial capsular plication reduces
translation and engagement similarly to remplissage, without any restriction in
motion.
PMID- 28402761
TI - Dyskeratosis Congenita.
PMID- 28402762
TI - Ticagrelor versus Clopidogrel in Peripheral Artery Disease.
PMID- 28402763
TI - Ticagrelor versus Clopidogrel in Peripheral Artery Disease.
PMID- 28402764
TI - Ensuring Access to Injectable Generic Drugs - The Case of Intravesical BCG for
Bladder Cancer.
PMID- 28402765
TI - Case 11-2017 - A 61-Year-Old Woman with Leg Swelling, Back Pain, and
Hydronephrosis.
PMID- 28402766
TI - Increase in the Incidence of Diabetes and Its Implications.
PMID- 28402767
TI - Who Decides When a Patient Can't? Statutes on Alternate Decision Makers.
PMID- 28402768
TI - Primary Hyperoxaluria.
PMID- 28402769
TI - Arrhythmogenic Right Ventricular Cardiomyopathy.
PMID- 28402770
TI - Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes.
AB - BACKGROUND: Long-term trends in excess risk of death and cardiovascular outcomes
have not been extensively studied in persons with type 1 diabetes or type 2
diabetes. METHODS: We included patients registered in the Swedish National
Diabetes Register from 1998 through 2012 and followed them through 2014. Trends
in deaths and cardiovascular events were estimated with Cox regression and
standardized incidence rates. For each patient, controls who were matched for
age, sex, and county were randomly selected from the general population. RESULTS:
Among patients with type 1 diabetes, absolute changes during the study period in
the incidence rates of sentinel outcomes per 10,000 person-years were as follows:
death from any cause, -31.4 (95% confidence interval [CI], -56.1 to -6.7); death
from cardiovascular disease, -26.0 (95% CI, -42.6 to -9.4); death from coronary
heart disease, -21.7 (95% CI, -37.1 to -6.4); and hospitalization for
cardiovascular disease, -45.7 (95% CI, -71.4 to -20.1). Absolute changes per
10,000 person-years among patients with type 2 diabetes were as follows: death
from any cause, -69.6 (95% CI, -95.9 to -43.2); death from cardiovascular
disease, -110.0 (95% CI, -128.9 to -91.1); death from coronary heart disease,
91.9 (95% CI, -108.9 to -75.0); and hospitalization for cardiovascular disease,
203.6 (95% CI, -230.9 to -176.3). Patients with type 1 diabetes had roughly 40%
greater reduction in cardiovascular outcomes than controls, and patients with
type 2 diabetes had roughly 20% greater reduction than controls. Reductions in
fatal outcomes were similar in patients with type 1 diabetes and controls,
whereas patients with type 2 diabetes had smaller reductions in fatal outcomes
than controls. CONCLUSIONS: In Sweden from 1998 through 2014, mortality and the
incidence of cardiovascular outcomes declined substantially among persons with
diabetes, although fatal outcomes declined less among those with type 2 diabetes
than among controls. (Funded by the Swedish Association of Local Authorities and
Regions and others.).
PMID- 28402771
TI - Autochthonous Japanese Encephalitis with Yellow Fever Coinfection in Africa.
PMID- 28402772
TI - Delays in Emergency Care and Mortality during Major U.S. Marathons.
AB - BACKGROUND: Large marathons frequently involve widespread road closures and
infrastructure disruptions, which may create delays in emergency care for
nonparticipants with acute medical conditions who live in proximity to marathon
routes. METHODS: We analyzed Medicare data on hospitalizations for acute
myocardial infarction or cardiac arrest among Medicare beneficiaries (>=65 years
of age) in 11 U.S. cities that were hosting major marathons during the period
from 2002 through 2012 and compared 30-day mortality among the beneficiaries who
were hospitalized on the date of a marathon, those who were hospitalized on the
same day of the week as the day of the marathon in the 5 weeks before or the 5
weeks after the marathon, and those who were hospitalized on the same day as the
marathon but in surrounding ZIP Code areas unaffected by the marathon. We also
analyzed data from a national registry of ambulance transports and investigated
whether ambulance transports occurring before noon in marathon-affected areas
(when road closures are likely) had longer scene-to-hospital transport times than
on nonmarathon dates. We also compared transport times on marathon dates with
those on nonmarathon dates in these same areas during evenings (when roads were
reopened) and in areas unaffected by the marathon. RESULTS: The daily frequency
of hospitalizations was similar on marathon and nonmarathon dates (mean number of
hospitalizations per city, 10.6 and 10.5, respectively; P=0.71); the
characteristics of the beneficiaries hospitalized on marathon and nonmarathon
dates were also similar. Unadjusted 30-day mortality in marathon-affected areas
on marathon dates was 28.2% (323 deaths in 1145 hospitalizations) as compared
with 24.9% (2757 deaths in 11,074 hospitalizations) on nonmarathon dates
(absolute risk difference, 3.3 percentage points; 95% confidence interval, 0.7 to
6.0; P=0.01; relative risk difference, 13.3%). This pattern persisted after
adjustment for covariates and in an analysis that included beneficiaries who had
five or more chronic medical conditions (a group that is unlikely to be
hospitalized because of marathon participation). No significant differences were
found with respect to where patients were hospitalized or the treatments they
received in the hospital. Ambulance scene-to-hospital transport times for pickups
before noon were 4.4 minutes longer on marathon dates than on nonmarathon dates
(relative difference, 32.1%; P=0.005). No delays were found in evenings or in
marathon-unaffected areas. CONCLUSIONS: Medicare beneficiaries who were admitted
to marathon-affected hospitals with acute myocardial infarction or cardiac arrest
on marathon dates had longer ambulance transport times before noon (4.4 minutes
longer) and higher 30-day mortality than beneficiaries who were hospitalized on
nonmarathon dates. (Funded by the National Institutes of Health.).
PMID- 28402774
TI - Changes in France's Deferral of Blood Donation by Men Who Have Sex with Men.
PMID- 28402776
TI - Lessons from Standing Rock - Of Water, Racism, and Solidarity.
PMID- 28402775
TI - The Blood Supply and Men Who Have Sex with Men.
PMID- 28402773
TI - Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012.
AB - BACKGROUND: Diagnoses of type 1 and type 2 diabetes in youths present a
substantial clinical and public health burden. The prevalence of these diseases
increased in the 2001-2009 period, but data on recent incidence trends are
lacking. METHODS: We ascertained cases of type 1 and type 2 diabetes mellitus at
five study centers in the United States. Denominators (4.9 million youths
annually) were obtained from the U.S. Census or health-plan member counts. After
the calculation of annual incidence rates for the 2002-2012 period, we analyzed
trends using generalized autoregressive moving-average models with 2-year moving
averages. RESULTS: A total of 11,245 youths with type 1 diabetes (0 to 19 years
of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified.
Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4%
annually (from 19.5 cases per 100,000 youths per year in 2002-2003 to 21.7 cases
per 100,000 youths per year in 2011-2012, P=0.03). In adjusted pairwise
comparisons, the annual rate of increase was greater among Hispanics than among
non-Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates
of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths
per year in 2002-2003 to 12.5 cases per 100,000 youths per year in 2011-2012,
P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted
pairwise comparisons showed that the relative annual increase in the incidence of
type 2 diabetes among non-Hispanic whites (0.6%) was lower than that among non
Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for
all comparisons) and that the annual rate of increase among Hispanics differed
significantly from that among Native Americans (3.1% vs. 8.9%, P=0.01). After
adjustment for age, sex, and race or ethnic group, the relative annual increase
in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2
diabetes was 4.8% (P<0.001). CONCLUSIONS: The incidences of both type 1 and type
2 diabetes among youths increased significantly in the 2002-2012 period,
particularly among youths of minority racial and ethnic groups. (Funded by the
National Institute of Diabetes and Digestive and Kidney Diseases and the Centers
for Disease Control and Prevention.).
PMID- 28402777
TI - Netting Insights into Fibrosis.
PMID- 28402778
TI - Mechanisms, Pathophysiology, and Management of Obesity.
PMID- 28402779
TI - Mechanisms, Pathophysiology, and Management of Obesity.
PMID- 28402780
TI - Mechanisms, Pathophysiology, and Management of Obesity.
PMID- 28402781
TI - Diagnosis and Differential Diagnosis of Cushing's Syndrome.
PMID- 28402782
TI - Ecology and pathology of Phytophthora ITS clade 3 species in forests in western
Oregon, USA.
AB - Phytophthora species are widespread and diverse in forest ecosystems, but little
is known about their ecology. We explore ecological attributes of the closely
related clade 3 species that occur sympatrically in western North American
forests. We address the population structure, pathology, and epidemiology of P.
ilicis, P. nemorosa, P. pluvialis, P. pseudosyringae, and P. psychrophila.
Phytophthora species were isolated from plant tissues, rainwater falling through
the forest canopy, streams, and soils in forests in western Oregon. Species
identifications were based on morphology in culture with molecular confirmation
using COX spacer and internal transcribed spacer (ITS) sequences. All five clade
3 Phytophthora species are present in western Oregon forests, although P. ilicis
(only 1 forest isolate) and P. psychrophila (only 12 isolates) are apparently
rare. P. ilicis is known only from holly in horticultural situations and once
from a naturalized seedling in an urban forest. The known distribution of P.
nemorosa in forest settings coincides with the ranges of its principle hosts,
tanoak and myrtlewood, in Oregon and California. Although it is regularly
identified from streams within the tanoak range, it has not been recovered from
streams beyond that range. P. pluvialis is primarily associated with Douglas-fir
canopies. It was identified from scattered locations throughout western Oregon in
rain traps beneath Douglas-fir plantations and from diseased needles. P.
pseudosyringae is also isolated from tanoak and myrtlewood in southwest Oregon
and California, but its distribution, in streams at least, extends throughout
much of western Oregon. P. psychrophila in Oregon is known only from rain traps
beneath tanoak trees. Little intraspecific variation was detected in the nuclear
rDNA ITS of clade 3 species. Variation in the mitochondrial COX spacer region was
more frequent, with 2 to 10 haplotypes identified in the clade 3 species, for
which we had multiple isolates.
PMID- 28402783
TI - Taxonomic divergence of the green naked-stipe members of the genus Microglossum
(Helotiales).
AB - Four new species of the Ascomycete genus Microglossum are recognized, based on
morphological characters and DNA sequences of nuc rDNA (ITS region and 28S gene)
and the second largest subunit of RNA polymerase II (RPB2). They differ from
Microglossum nudipes by the color of the ascocarps and the sizes and shapes of
ascospores, asci, and paraphyses. A lectotype is proposed, and an emended
description is provided for M. nudipes. Descriptions of new species Microglossum
clavatum, M. truncatum, M. pretense, and M. tenebrosum are provided. Other
closely related species in the group of green earth tongues include Microglossum
viride, M. rickii, and M. griseoviride. An identification key to green
Microglossum species is presented.
PMID- 28402784
TI - Defining the pathways of symbiotic Epichloe colonization in grass embryos with
confocal microscopy.
AB - Asexual cool-season grass endophytes of the genus Epichloe (Ascomycota:
Clavicipitaceae) are strictly vertically disseminated. The hosts of these
mutualistic fungi express no symptoms during the fungal lifecycle that takes
place entirely within the plant, while their hosts receive beneficial outcomes.
These fungi are distributed in two major locations within the mature seeds of
their hosts; namely, within the embryo (including the scutellum, coleoptile,
plumule, radicle, and coleorhiza tissues) and between the aleurone and pericarp
layers, with the latter hyphae playing no role in transmission of the fungus to
the next plant generation. Conflicting evidence remains in the literature on the
timing of embryo colonization. In a detailed investigation, utilizing confocal
microscopy to observe the distribution of Epichloe coenophiala strain AR601 in
tall fescue (Lolium arundinaceum), we tracked endophyte hyphal colonization in
the ovary (pre-fertilization) through to the fully mature seed stage. Confocal
microscopy images revealed that at the early and mature developmental stages of
the embryo sac, before host grass fertilization, there were large quantities of
endophyte mycelium present, especially around the antipodal cells, indicating
that this endophyte enters the embryo sac before the fertilization stage. After
host fertilization, fungal hyphae could be seen in the true embryo and early
nonstarchy endosperm. Understanding the mechanisms of transmission to the seed is
important for commercial seed producers and end users.
PMID- 28402785
TI - Erratum.
PMID- 28402788
TI - Ustilago maydis, the corn smut fungus, has an unusual diploid mitotic stage.
AB - Ustilago maydis causes common smut disease in maize. Although pathogenic diploid
strains of the fungus have been known for many years, the normal life cycle was
thought to involve an extended dikaryotic stage, with nuclear fusion occurring in
immature teliospores. However, microscopic examination of both living and fixed
tumor material showed that nuclei fuse long before sporulation begins and that
tumors are filled with uninucleate cells undergoing mitosis. Quantification of
DNA in the nuclei confirmed these observations. Additionally, fungal cells from
tumor material placed on nutrient agar produced colonies of diploid budding
cells. Time-lapse observations showed that at least some of these colonies arose
from thin-walled fungal cells rather than from immature spores. Ultrastructural
examination of developing teliospores from tumors confirmed that they were
uninucleate. Condensed chromatin and other structures characteristic of nuclei in
prophase I of meiosis were observed. These observations support revising the U.
maydis life cycle to include a diploid mitotic stage that corresponds with rapid
tumor enlargement and conversion of plant to fungal biomass. Because mitotic
division of diploid nuclei is so unusual as a life cycle feature in the fungi, it
will be interesting to explore the consequences of its presence in U. maydis.
PMID- 28402787
TI - Structural character evolution in Pucciniomycotina: mitosis, septa, and hyphal
branch initiation in two Helicogloea species.
AB - Early diverging taxa of Ascomycota and Basidiomycota share similarities in
subcellular characters of the spindle pole body (SPB), nuclear division, and
septal pore apparatus, but our understanding of character evolution is incomplete
because of the limited number of structural studies within the earliest diverging
subphyla of Dikarya, Taphrinomycotina and Pucciniomycotina. Two species of
Helicogloea (Atractiellomycetes) were analyzed for these characters and provide
data on SPB and nuclear division for an additional class of Pucciniomycotina. A
detailed analysis of septal pore apparatus for the Helicogloea species permits
comparisons with those of other Pucciniomycotina and Ascomycota. The endogenous
origin of hyphal branches is shown to occur in a third class of Pucciniomycotina.
The full set of characters supports a close relationship between
Atractiellomycetes and Pucciniomycetes.
PMID- 28402786
TI - Atractiella rhizophila, sp. nov., an endorrhizal fungus isolated from the Populus
root microbiome.
AB - Among fungi isolated from healthy root mycobiomes of Populus, we discovered a new
endorrhizal fungal species belonging to the rust lineage Pucciniomycotina,
described here as Atractiella rhizophila. We characterized this species by
transmission electron microscopy (TEM), phylogenetic analysis, and plant bioassay
experiments. Phylogenetic sequence analysis of isolates and available
environmental and reference sequences indicates that this new species, A.
rhizophila, has a broad geographic and host range. Atractiella rhizophila appears
to be present in North America, Australia, Asia, and Africa and is associated
with trees, orchids, and other agriculturally important species, including
soybean, corn, and rice. Despite the large geographic and host range of this
species sampling, A. rhizophila appears to have exceptionally low sequence
variation within nuclear rDNA markers examined. With inoculation studies, we
demonstrate that A. rhizophila is nonpathogenic, asymptomatically colonizes plant
roots, and appears to foster plant growth and elevated photosynthesis rates.
PMID- 28402789
TI - Rust fungi on Panicum.
AB - Rusts are economically important diseases of switchgrass (Panicum virgatum) and
other Paniceae grasses. Phylogenetic analyses based on sequences of the nuc rDNA
5.8S internal transcribed spacer 2 region (ITS2), partial 28S region, and
intergenic spacer region (IGS) of nuc rDNA showed that species of rust fungi
infecting switchgrass are closely related within Puccinia. Variation among rbcLa
sequences for the associated hosts sampled concurred with the original
identifications. Five species infecting switchgrass were recognized: Puccinia
graminicola (= Uromyces graminicola), P. pammelii (= P. panici), and the proposed
new species P. amari, P. novopanici, and P. pascua. These species were distinct
from P. emaculata, the species previously considered the principal rust pathogen
infecting switchgrass but that was found exclusively on witchgrass (Panicum
capillare) in this study. Rust fungi on switchgrass previously identified as P.
emaculata were identified as the morphologically similar species P. amari, P.
novopanici, and P. pammelii. The morphological species Puccinia graminicola was
found to comprise three species, P. graminicola and the proposed new species P.
pascua on switchgrass and P. cumminsii on Panicum sp.
PMID- 28402790
TI - Plant diversity and plant identity influence Fusarium communities in soil.
AB - Fusarium communities play important functional roles in soil and in plants as
pathogens, endophytes, and saprotrophs. This study tests how rhizosphere Fusarium
communities may vary with plant species, changes in the diversity of the
surrounding plant community, and soil physiochemical characteristics. Fusarium
communities in soil associated with the roots of two perennial prairie plant
species maintained as monocultures or growing within polyculture plant
communities were characterized using targeted metagenomics. Amplicon libraries
targeting the RPB2 locus were generated from rhizosphere soil DNAs and sequenced
using pyrosequencing. Sequences were clustered into operational taxonomic units
(OTUs) and assigned a taxonomy using the Evolutionary Placement Algorithm.
Fusarium community composition was differentiated between monoculture and
polyculture plant communities, and by plant species in monoculture, but not in
polyculture. Taxonomic classification of the Fusarium OTUs showed a predominance
of F. tricinctum and F. oxysporum as well of the presence of a clade previously
only found in the Southern Hemisphere. Total Fusarium richness was not affected
by changes in plant community richness or correlated with soil physiochemical
characteristics. However, OTU richness within two predominant phylogenetic
lineages within the genus was positively or negatively correlated with soil
physiochemical characteristics among samples within each lineage. This work shows
that plant species, plant community richness, and soil physiochemical
characteristics may all influence the composition and richness of Fusarium
communities in soil.
PMID- 28402791
TI - Survey of corticioid fungi in North American pinaceous forests reveals
hyperdiversity, underpopulated sequence databases, and species that are
potentially ectomycorrhizal.
AB - The corticioid fungi are commonly encountered, highly diverse, ecologically
important, and understudied. We collected specimens in 60 pine and spruce forests
across North America to survey corticioid fungal frequency and distribution and
to compile an internal transcribed spacer (ITS) database for the group. Sanger
sequences from the ITS region of vouchered specimens were compared with sequences
on GenBank and UNITE, and with high-throughput sequence data from soil and roots
taken at the same sites. Out of 425 high-quality Sanger sequences from vouchered
specimens, we recovered 223 distinct operational taxonomic units (OTUs), the
majority of which could not be assigned to species by matching to the BLAST
database. Corticioid fungi were found to be hyperdiverse, as supported by the
observations that nearly two-thirds of our OTUs were represented by single
collections and species estimator curves showed steep slopes with no plateaus. We
estimate that 14.8-24.7% of our voucher-based OTUs are likely to be
ectomycorrhizal (EM). Corticioid fungi recovered from the soil formed a different
community assemblage, with EM taxa accounting for 40.5-58.6% of OTUs. We compared
basidioma sequences with EM root tips from our data, GenBank, or UNITE, and with
this approach, we reiterate existing speculations that Trechispora stellulata is
EM. We found that corticioid fungi have a significant distance-decay pattern,
adding to the literature supporting fungi as having geographically structured
communities. This study provides a first view of the diversity of this important
group across North American pine forests, but much of the biology and taxonomy of
these diverse, important, and widespread fungi remains unknown.
PMID- 28402792
TI - Erratum.
PMID- 28402793
TI - Lichenomphalia altoandina, a new species of Hygrophoraceae from the Chilean
Altiplano.
AB - Lichenomphalia is a lichenized agaric genus characterized by its omphalinoid
basidiomes. Lichenomphalia species are associated with unicellular green algae in
the genus Coccomyxa and are mainly distributed in polar and alpine habitats. The
aim of this work is to describe L. altoandina, a new species from northern Chile
that grows among cushion plants over 3000 m above sea level in the Andes
Mountains. The species is remarkable for living in highly saline environments, in
some cases virtually on salt crusts. Lichenomphalia altoandina differs from other
known species and particularly from L. aurantiaca, the most morphologically
similar species, in its smooth and broader stipe and its slightly larger spores.
Lichenomphalia altoandina is also morphologicaly and ecologically more similar to
the core Lichenomphalia clade. Our phylogenetic study based on nuclear rDNA ITS
and partial 28S sequences shows that L. altoandina belongs to the
Protolichenomphalia clade and is sister to an unknown lineage, L. aff.
umbellifera, from New Zealand.
PMID- 28402794
TI - Increased phylogenetic resolution within the ecologically important Rhizopogon
subgenus Amylopogon using 10 anonymous nuclear loci.
AB - Rhizopogon species are ecologically significant ectomycorrhizal fungi in conifer
ecosystems. The importance of this system merits the development and utilization
of a more robust set of molecular markers specifically designed to evaluate their
evolutionary ecology. Anonymous nuclear loci (ANL) were developed for R. subgenus
Amylopogon. Members of this subgenus occur throughout the United States and are
exclusive fungal symbionts associated with Pterospora andromedea, a threatened
mycoheterotrophic plant endemic to disjunct eastern and western regions of North
America. Candidate ANL were developed from 454 shotgun pyrosequencing and
assessed for positive amplification across targeted species, sequencing success,
and recovery of phylogenetically informative sites. Ten ANL were successfully
developed and were subsequently used to sequence representative taxa, herbaria
holotype and paratype specimens in R. subgenus Amylopogon. Phylogenetic
reconstructions were performed on individual and concatenated data sets by
Bayesian inference and maximum likelihood methods. Phylogenetic analyses of these
10 ANL were compared with a phylogeny traditionally constructed using the
universal fungal barcode nuc rDNA ITS1-5.8S-ITS2 region (ITS). The resulting ANL
phylogeny was consistent with most of the species designations delineated by ITS.
However, the ANL phylogeny provided much greater phylogenetic resolution,
yielding new evidence for cryptic species within previously defined species of R.
subgenus Amylopogon. Additionally, the rooted ANL phylogeny provided an alternate
topology to the ITS phylogeny, which inferred a novel set of evolutionary
relationships not identified in prior phylogenetic studies.
PMID- 28402795
TI - Global diversity and phylogeny of Onnia (Hymenochaetaceae) species on
gymnosperms.
AB - Onnia includes white rotting polypores with annual basidiocarps, a duplex
context, monomitic hyphal structure, hymenial setae, and hyaline, thin-walled,
smooth basidiospores. Specimens of Onnia, originating mainly from East Asia,
Europe, and North America, were studied using both morphology and phylogenetic
analyses. Our concatenated data set was derived from 25 collections and included
(i) 25 nuc rDNA internal transcribed spacer region sequences (ITS1-5.8S-ITS2 =
ITS), 17 generated in this study; and (ii) 14 nuc rDNA 28S rDNA sequences,
including the D1-D2 domains, 11 of them generated in this study. The resulting
maximum likelihood and Bayesian phylogenies recovered all sampled collections of
Onnia as a well-supported clade. In this clade, three previously accepted
species, viz., Onnia leporina, O. tomentosa, and O. triquetra, received strong
support, whereas three additional lineages with strong support represent the new
species described in this paper, O. subtriquetra, O. microspora, and O. tibetica.
Of the six Onnia species occurring on gymnosperms, O. tomentosa and O. leporina
grow mainly on Picea and have circumboreal distribution in the Northern
Hemisphere. In contrast, other species that mostly grow on Pinus are
geographically restricted to limited regions, viz., O. triquetra in Europe, O.
subtriquetra in North America, and O. microspora and O. tibetica in Asia.
PMID- 28402796
TI - Insights into the phylogeny of Northern Hemisphere Armillaria: Neighbor-net and
Bayesian analyses of translation elongation factor 1-alpha gene sequences.
AB - Armillaria possesses several intriguing characteristics that have inspired wide
interest in understanding phylogenetic relationships within and among species of
this genus. Nuclear ribosomal DNA sequence-based analyses of Armillaria provide
only limited information for phylogenetic studies among widely divergent taxa.
More recent studies have shown that translation elongation factor 1-alpha (tef1)
sequences are highly informative for phylogenetic analysis of Armillaria species
within diverse global regions. This study used Neighbor-net and coalescence-based
Bayesian analyses to examine phylogenetic relationships of newly determined and
existing tef1 sequences derived from diverse Armillaria species from across the
Northern Hemisphere, with Southern Hemisphere Armillaria species included for
reference. Based on the Bayesian analysis of tef1 sequences, Armillaria species
from the Northern Hemisphere are generally contained within the following four
superclades, which are named according to the specific epithet of the most
frequently cited species within the superclade: (i) Socialis/Tabescens
(exannulate) superclade including Eurasian A. ectypa, North American A. socialis
(A. tabescens), and Eurasian A. socialis (A. tabescens) clades; (ii) Mellea
superclade including undescribed annulate North American Armillaria sp. (Mexico)
and four separate clades of A. mellea (Europe and Iran, eastern Asia, and two
groups from North America); (iii) Gallica superclade including Armillaria Nag E
(Japan), multiple clades of A. gallica (Asia and Europe), A. calvescens (eastern
North America), A. cepistipes (North America), A. altimontana (western USA), A.
nabsnona (North America and Japan), and at least two A. gallica clades (North
America); and (iv) Solidipes/Ostoyae superclade including two A.
solidipes/ostoyae clades (North America), A. gemina (eastern USA), A.
solidipes/ostoyae (Eurasia), A. cepistipes (Europe and Japan), A. sinapina (North
America and Japan), and A. borealis (Eurasia) clade 2. Of note is that A.
borealis (Eurasia) clade 1 appears basal to the Solidipes/Ostoyae and Gallica
superclades. The Neighbor-net analysis showed similar phylogenetic relationships.
This study further demonstrates the utility of tef1 for global phylogenetic
studies of Armillaria species and provides critical insights into multiple
taxonomic issues that warrant further study.
PMID- 28402798
TI - Morphological and molecular evidence for three new species of Coltricia
(Hymenochaetaceae, Basidiomycota) from southern China.
AB - Three new species of Coltricia from southern China are described on the basis of
morphological characters and molecular analyses. Phylogenetic analyses based on
nuc rDNA ITS1-5.8S-ITS2 and partial 28S rDNA, and partial sequences of genes for
RNA polymerase II subunits 1 and 2 confirmed the generic placement of the three
new species. Coltricia lateralis is characterized by small, laterally stipitate
basidiocarps, obtuse pileus margin, cinnamon-buff to honey yellow pore surface,
and broadly ellipsoid basidiospores that measure 7-8 * 5-6 um. Coltricia rigida
is characterized by large, woody-hard fan-shaped basidiocarps, small pores (7-8
per mm), presence of septate sclerified hyphae, and subglobose to globose
basidiospores that measure 6-7 * 5-6.5 MUm. Coltricia wenshanensis is
characterized by centrally stipitate basidiocarps, a distinctly concentrically
zonate and sulcate pileal surface, large pores (0.5-2 per mm), and broadly
ellipsoid to subglobose basidiospores that measure 7.5-8 * 6-7 um.
PMID- 28402797
TI - Three new species of Calocybe (Agaricales, Basidiomycota) from northeastern China
are supported by morphological and molecular data.
AB - Three new species, Calocybe aurantiaca, C. convexa, and C. decolorata, are
described based on collections made in Shenyang City, Liaoning Province, China.
The main characters of C. aurantiaca are its orange-yellow sporocarps and small
and smooth basidiospores. Calocybe convexa is characterized by its orange-buff
pileus, very small basidiospores, and tortuous stipe, whereas C. decolorata is
mainly characterized by its gills that turn blue when bruised. The sequences of
nuc rDNA ITS1-5.8S-ITS2 (ITS) and the 28S D1-D5 region of the Calocybe species
were analyzed, and the results indicated that the three new species belonged to
the genus Calocybe and differed from other species of Calocybe. The morphological
similarities of the new species to other Calocybe species and the classification
system within the genus Calocybe based on molecular data are also discussed. A
key is provided for the Calocybe species as reported from China in order to
facilitate future studies of the genus.
PMID- 28402799
TI - Implementation of an integrated primary care cardiometabolic risk prevention and
management network in Montreal: does greater coordination of care with primary
care physicians have an impact on health outcomes?
AB - INTRODUCTION: Chronic disease management requires substantial services
integration. A cardiometabolic risk management program inspired by the Chronic
Care Model was implemented in Montreal for patients with diabetes or
hypertension. One of this study's objectives was to assess the impact of care
coordination between the interdisciplinary teams and physicians on patient
participation in the program, lifestyle improvements and disease control.
METHODS: We obtained data on health outcomes from a register of clinical data,
questionnaires completed by patients upon entry into the program and at the 12
month mark, and we drew information on the program's characteristics from the
implementation analysis. We conducted multiple regression analyses, controlling
for patient sociodemographic and health characteristics, to measure the
association between interdisciplinary team coordination with primary care
physicians and various health outcomes. RESULTS: A total of 1689 patients took
part in the study (60.1% participation rate). Approximately 40% of patients
withdrew from the program during the first year. At the 12-month follow-up (n =
992), we observed a significant increase in the proportion of patients achieving
the various clinical targets. The perception by the interdisciplinary team of
greater care coordination with primary care physicians was associated with
increased participation in the program and the achievement of better clinical
results. CONCLUSION: Greater coordination of patient services between
interdisciplinary teams and primary care physicians translates into benefits for
patients.
PMID- 28402802
TI - Positive Mental Health Surveillance Indicator Framework: Quick Stats, Youth (12
to 17 years of age), Canada, 2017 Edition.
PMID- 28402801
TI - Measuring positive mental health in Canada: construct validation of the Mental
Health Continuum-Short Form.
AB - INTRODUCTION: Positive mental health is increasingly recognized as an important
focus for public health policies and programs. In Canada, the Mental Health
Continuum-Short Form (MHC-SF) was identified as a promising measure to include on
population surveys to measure positive mental health. It proposes to measure a
three-factor model of positive mental health including emotional, social and
psychological well-being. The purpose of this study was to examine whether the
MHC-SF is an adequate measure of positive mental health for Canadian adults.
METHODS: We conducted confirmatory factor analysis (CFA) using data from the 2012
Canadian Community Health Survey (CCHS)-Mental Health Component (CCHS-MH), and
cross-validated the model using data from the CCHS 2011-2012 annual cycle. We
examined criterion-related validity through correlations of MHC-SF subscale
scores with positively and negatively associated concepts (e.g. life satisfaction
and psychological distress, respectively). RESULTS: We confirmed the validity of
the three-factor model of emotional, social and psychological well-being through
CFA on two independent samples, once four correlated errors between items on the
social well-being scale were added. We observed significant correlations in the
anticipated direction between emotional, psychological and social well-being
scores and related concepts. Cronbach's alpha for both emotional and
psychological well-being subscales was 0.82; for social well-being it was 0.77.
CONCLUSION: Our study suggests that the MHC-SF measures a three-factor model of
positive mental health in the Canadian population. However, caution is warranted
when using the social well-being scale, which did not function as well as the
other factors, as evidenced by the need to add several correlated error terms to
obtain adequate model fit, a higher level of missing data on these questions and
weaker correlations with related constructs. Social well-being is important in a
comprehensive measure of positive mental health, and further research is
recommended.
PMID- 28402800
TI - Assessment of dysglycemia risk in the Kitikmeot region of Nunavut: using the
CANRISK tool.
AB - INTRODUCTION: The Public Health Agency of Canada adapted a Finnish diabetes
screening tool (FINDRISC) to create a tool (CANRISK) tailored to Canada's multi
ethnic population. CANRISK was developed using data collected in seven Canadian
provinces. In an effort to extend the applicability of CANRISK to northern
territorial populations, we completed a study with the mainly Inuit population in
the Kitikmeot region of Nunavut. METHODS: We obtained CANRISK questionnaires,
physical measures and blood samples from participants in five Nunavut communities
in Kitikmeot. We used logistic regression to test model fit using the original
CANRISK risk factors for dysglycemia (prediabetes and diabetes). Dysglycemia was
assessed using fasting plasma glucose (FPG) alone and/or oral glucose tolerance
test. We generated participants' CANRISK scores to test the functioning of this
tool in the Inuit population. RESULTS: A total of 303 individuals participated in
the study. Half were aged less than 45 years, two-thirds were female and 84% were
Inuit. A total of 18% had prediabetes, and an additional 4% had undiagnosed
diabetes. The odds of having dysglycemia rose exponentially with age, while the
relationship with BMI was U-shaped. Compared with lab test results, using a cut
off point of 32 the CANRISK tool achieved a sensitivity of 61%, a specificity of
66%, a positive predictive value of 34% and an accuracy rate of 65%. CONCLUSION:
The CANRISK tool achieved a similar accuracy in detecting dysglycemia in this
mainly Inuit population as it did in a multi-ethnic sample of Canadians. We found
the CANRISK tool to be adaptable to the Kitikmeot region, and more generally to
Nunavut.
PMID- 28402803
TI - America, all things not being equal.
PMID- 28402804
TI - Urbanisation, inequality, and health in Asia and the Pacific.
PMID- 28402805
TI - Physician burnout: let's talk.
PMID- 28402806
TI - An agenda to fight inequality.
PMID- 28402807
TI - Urgent action needed on health inequities among American Indians and Alaska
Natives.
PMID- 28402808
TI - Eliminating maternal and neonatal tetanus and closing the immunity gap.
PMID- 28402809
TI - The Lancet Child & Adolescent Health: a call for papers for a new journal.
PMID- 28402810
TI - Offline: Science and the defeat of fear.
PMID- 28402811
TI - Life in limbo for millions of stateless people worldwide.
PMID- 28402812
TI - David Himmelstein and Steffie Woolhandler: advocates for an equitable US health
system.
PMID- 28402813
TI - Sexual abuse and injury during incarceration reveal the need for re-entry trauma
screening.
PMID- 28402814
TI - Dana-Farber Cancer Institute holds fundraiser at Trump estate.
PMID- 28402815
TI - White individuals' risk of premature mortality in context.
PMID- 28402816
TI - Whole brain radiotherapy for non-small cell lung cancer.
PMID- 28402817
TI - Whole brain radiotherapy for non-small cell lung cancer.
PMID- 28402818
TI - Whole brain radiotherapy for non-small cell lung cancer - Authors' reply.
PMID- 28402819
TI - Cutaneous adverse events related to FreeStyle Libre device.
PMID- 28402820
TI - Cutaneous adverse events related to FreeStyle Libre device - Authors' reply.
PMID- 28402821
TI - Physician burnout is better conceptualised as depression.
PMID- 28402823
TI - Department of Error.
PMID- 28402822
TI - Department of Error.
PMID- 28402824
TI - Physician burnout is better conceptualised as depression - Authors' reply.
PMID- 28402825
TI - Inequality and the health-care system in the USA.
AB - Widening economic inequality in the USA has been accompanied by increasing
disparities in health outcomes. The life expectancy of the wealthiest Americans
now exceeds that of the poorest by 10-15 years. This report, part of a Series on
health and inequality in the USA, focuses on how the health-care system, which
could reduce income-based disparities in health, instead often exacerbates them.
Other articles in this Series address population health inequalities, and the
health effects of racism, mass incarceration, and the Affordable Care Act (ACA).
Poor Americans have worse access to care than do wealthy Americans, partly
because many remain uninsured despite coverage expansions since 2010 due to the
ACA. For individuals with private insurance, rising premiums and cost sharing
have undermined wage gains and driven many households into debt and even
bankruptcy. Meanwhile, the share of health-care resources devoted to care of the
wealthy has risen. Additional reforms that move forward, rather than backward,
from the ACA are sorely needed to mitigate health and health-care inequalities
and reduce the financial burdens of medical care borne by non-wealthy Americans.
PMID- 28402826
TI - The Affordable Care Act: implications for health-care equity.
AB - Inequalities in medical care are endemic in the USA. The Affordable Care Act
(ACA), passed in 2010 and fully implemented in 2014, was intended to expand
coverage and bring about a new era of health-care access. In this review, we
evaluate the legislation's impact on health-care equity. We consider the law's
coverage expansion, insurance market reforms, cost and affordability provisions,
and delivery-system reforms. Although the ACA improved coverage and access
particularly for poorer Americans, women, and minorities-its overall impact was
modest in comparison with the gaps present before the law's implementation.
Today, 29 million people in the USA remain uninsured, and substantial
inequalities in access along economic, gender, and racial lines persist. Although
most Americans agree that further reform is needed, the proper direction for
reform-especially following the 2016 presidential election-is highly contentious.
We discuss proposals for change from opposite sides of the political spectrum,
together with their potential impact on health equity.
PMID- 28402827
TI - Structural racism and health inequities in the USA: evidence and interventions.
AB - Despite growing interest in understanding how social factors drive poor health
outcomes, many academics, policy makers, scientists, elected officials,
journalists, and others responsible for defining and responding to the public
discourse remain reluctant to identify racism as a root cause of racial health
inequities. In this conceptual report, the third in a Series on equity and
equality in health in the USA, we use a contemporary and historical perspective
to discuss research and interventions that grapple with the implications of what
is known as structural racism on population health and health inequities.
Structural racism refers to the totality of ways in which societies foster racial
discrimination through mutually reinforcing systems of housing, education,
employment, earnings, benefits, credit, media, health care, and criminal justice.
These patterns and practices in turn reinforce discriminatory beliefs, values,
and distribution of resources. We argue that a focus on structural racism offers
a concrete, feasible, and promising approach towards advancing health equity and
improving population health.
PMID- 28402828
TI - Mass incarceration, public health, and widening inequality in the USA.
AB - In this Series paper, we examine how mass incarceration shapes inequality in
health. The USA is the world leader in incarceration, which disproportionately
affects black populations. Nearly one in three black men will ever be imprisoned,
and nearly half of black women currently have a family member or extended family
member who is in prison. However, until recently the public health implications
of mass incarceration were unclear. Most research in this area has focused on the
health of current and former inmates, with findings suggesting that incarceration
could produce some short-term improvements in physical health during imprisonment
but has profoundly harmful effects on physical and mental health after release.
The emerging literature on the family and community effects of mass incarceration
points to negative health impacts on the female partners and children of
incarcerated men, and raises concerns that excessive incarceration could harm
entire communities and thus might partly underlie health disparities both in the
USA and between the USA and other developed countries. Research into
interventions, policies, and practices that could mitigate the harms of
incarceration and the post-incarceration period is urgently needed, particularly
studies using rigorous experimental or quasi-experimental designs.
PMID- 28402829
TI - Population health in an era of rising income inequality: USA, 1980-2015.
AB - Income inequality in the USA has increased over the past four decades.
Socioeconomic gaps in survival have also increased. Life expectancy has risen
among middle-income and high-income Americans whereas it has stagnated among poor
Americans and even declined in some demographic groups. Although the increase in
income inequality since 1980 has been driven largely by soaring top incomes, the
widening of survival inequalities has occurred lower in the distribution-ie,
between the poor and upper-middle class. Growing survival gaps across income
percentiles since 2001 reflect falling real incomes among poor Americans as well
as an increasingly strong association between low income and poor health. Changes
in individual risk factors such as smoking, obesity, and substance abuse play a
part but do not fully explain the steeper gradient. Distal factors correlated
with rising inequality including unequal access to technological innovations,
increased geographical segregation by income, reduced economic mobility, mass
incarceration, and increased exposure to the costs of medical care might have
reduced access to salutary determinants of health among low-income Americans.
Having missed out on decades of income growth and longevity gains, low-income
Americans are increasingly left behind. Without interventions to decouple income
and health, or to reduce inequalities in income, we might see the emergence of a
21st century health-poverty trap and the further widening and hardening of
socioeconomic inequalities in health.
PMID- 28402831
TI - Department of Error.
PMID- 28402830
TI - Department of Error.
PMID- 28402832
TI - Early developmental exposure to pentachlorophenol causes alterations on mRNA
expressions of caspase protease family in zebrafish embryos.
AB - Caspase proteases play an essential role in cell apoptosis and inflammation, thus
matter greatly in animal development and other biological processes. As a
ubiquitous environmental pollutant, pentachlorophenol (PCP) is considered to have
adverse effects on animal apoptosis during embryonic development, yet the
evidence that PCP interfere with caspase genes was seldom reported. To uncover
the effects of PCP on caspases expression in early embryos of zebrafish, two
concentrations of PCP (5 MUg/L and 200 MUg/L) were chosen and 14 types of caspase
genes at two different developmental stages, 8 h post-fertilization (hpf) and 24
hpf were analyzed. Lower survival and hatching rates, distinct developmental
delay and morphological deformities of head and tail were observed. PCP,
especially in the high concentration, significantly altered the expressions of
most caspase genes. At 8 hpf, PCP had the most significant inductive effects on
gene casp8l2 with fold changes (FCs) of 6.87 at 5 MUg/L and 4.48 at 200 MUg/L,
and casp6l1 (with FCs of 3.15/3.69), and inhibitory effects on caspa (with FCs of
0.93/0.53) and caspb (with FCs of 0.99/0.57). At 24 hpf, PCP had the most
significant effects on casp6l2, casp9, and caspc. PCP exposure possibly disrupted
intrinsic apoptosis pathway considering its effects on casp9 expression. In
addition, most caspase genes exhibited higher levels at 24 hpf than 8 hpf except
caspc. Our results suggested that PCP had different effects on varied caspase
genes, which probably resulting in a profound impact on caspase proteins and
apoptosis processes and, ultimately, developmental abnormality.
PMID- 28402833
TI - Understanding the similarities and differences between ozone and peroxone in the
degradation of naphthenic acids: Comparative performance for potential treatment.
AB - Ozonation at high doses is a costly treatment for oil sands process-affected
water (OSPW) naphthenic acids (NAs) degradation. To decrease costs and limit
doses, different peroxone (hydrogen peroxide/ozone; H2O2:O3) processes using mild
ozone doses of 30 and 50 mg/L were investigated. The degradation efficiency of Ox
NAs (classical (O2-NAs) + oxidized NAs) improved from 58% at 30 mg/L ozone to
59%, 63% and 76% at peroxone (1:1), 50 mg/L ozone, and peroxone (1:2),
respectively. Suppressing the hydroxyl radical (*OH) pathway by adding tert-butyl
alcohol did significantly reduce the degradation in all treatments, while
molecular ozone contribution was around 50% and 34% for O2-NAs and Ox-NAs,
respectively. Structure reactivity toward degradation was observed with
degradation increase for both O2-NAs and Ox-NAs with increase of both carbon (n)
and hydrogen deficiency/or |-Z| numbers in all treatments. However, the combined
effect of n and Z showed specific insights and differences between ozone and
peroxone treatments. The degradation pathway for |-Z|>=10 isomers in ozone
treatments through molecular ozone was significant compared to *OH. Though
peroxone (1:2) highly reduced the fluorophore organics and toxicity to Vibrio
fischeri, the best oxidant utilization in the degradation of O2-NAs (mg/L) per
ozone dose (mg/L) was observed in the peroxone (1:1) (0.91) and 30 mg/L ozone
treatments (0.92). At n = 9-11, peroxone (1:1) had similar or enhanced effect on
the O2-NAs degradation compared to 50 mg/L ozone. Enhancing *OH pathway through
peroxone versus ozone may be an effective OSPW treatment that will allow its safe
release into receiving environments with marginal cost addition.
PMID- 28402834
TI - Long-term outcome of refractory status epilepticus in adults: A retrospective
population-based study.
AB - PURPOSE: Refractory status epilepticus (RSE) is a neurological emergency with
significant morbidity and mortality. We aimed to analyze the long-term outcome of
intensive care unit (ICU)-treated RSE and super-refractory status epilepticus
(SRSE) patients in a population based cohort. METHODS: A retrospective study of
ICU- and anesthesia-treated RSE patients in Kuopio University Hospital's (KUH)
special responsibility area hospitals in the central and eastern part of Finland
from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH's catchment area consists
of five hospitals-one university hospital and four central hospitals-and covers a
population of 840 000. We included all consecutive adult (16 years or older) RSE
patients admitted in the participating ICUs during the 3-year period and excluded
patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a
long-term (1-year) outcome measure: good (mRS 0-3, recovered to baseline
function) or poor (mRS 4-6, major functional deficit or death). KEY FINDINGS: We
identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an
annual incidence of 3.0 (95% confidence interval (CI) 2.4-3.8). 21% of the
patients were classified as SRSE, with the annual incidence being 0.6/100 000
(95% CI 0.4-1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7%
(95% CI 1.2%-12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%-32.5%)
(n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed
neurological deficit at 1year. Poor outcome (mRS 4-6) was recorded for 52% (n=39)
of the patients. Older age was associated with poorer outcome at 1year (p=0.03).
For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3)
(95%CI 0%-38.2%). SIGNIFICANCE: During 1-year follow-up, nearly 50% of the ICU
treated RSE patients recovered to baseline function, whereas 30% showed new
functional defects and 20% died. SRSE does not have a necessarily poorer outcome.
The outcome is worse in older patients and in patients with progressive or fatal
etiologies. SE should be treated with generalized anesthesia only in refractory
cases after failure of adequately used first- and second-line antiepileptic
drugs.
PMID- 28402835
TI - iPSC-Derived Retina Transplants Improve Vision in rd1 End-Stage Retinal
Degeneration Mice.
PMID- 28402836
TI - Reproducibility and diagnostic performance of shear wave elastography in
evaluating breast solid mass.
AB - Shear wave elastography (SWE) was performed independently by two radiologists in
264 solid breast masses. The images were reviewed for color overlay pattern (COP)
classification by the two radiologists, double blinded to any information. The
interobserver agreement of the COP was almost perfect (kappa=0.908) and high in
Emax (ICC=0.89). The AUC value of the COP (0.954) was significantly higher than
that of Emax (0.915) (p=0.002) but not significantly different from that of Emax
combined with COP (0.957) (p=0.098). The SWE color overlay pattern and Emax of
breast masses were highly reproducible. The COP had better diagnostic ability
than Emax, suggesting that COP may be a more reliable parameter for solid breast
mass evaluation.
PMID- 28402837
TI - A critical examination of the possible application of zinc stable isotope ratios
in bivalve mollusks and suspended particulate matter to trace zinc pollution in a
tropical estuary.
AB - The application of zinc (Zn) isotopes in bivalve tissues to identify zinc sources
in estuaries was critically assessed. We determined the zinc isotope composition
of mollusks (Crassostrea brasiliana and Perna perna) and suspended particulate
matter (SPM) in a tropical estuary (Sepetiba Bay, Brazil) historically impacted
by metallurgical activities. The zinc isotope systematics of the SPM was in line
with mixing of zinc derived from fluvial material and from metallurgical
activities. In contrast, source mixing alone cannot account for the isotope
ratios observed in the bivalves, which are significantly lighter in the
contaminated metallurgical zone (delta66ZnJMC = +0.49 +/- 0.060/00, 2sigma, n =
3) compared to sampling locations outside (delta66ZnJMC = +0.83 +/- 0.100/00,
2sigma, n = 22). This observation suggests that additional factors such as
speciation, bioavailability and bioaccumulation pathways (via solution or
particulate matter) influence the zinc isotope composition of bivalves.
PMID- 28402838
TI - Exposure of honey bees (Apis mellifera) to different classes of insecticides
exhibit distinct molecular effect patterns at concentrations that mimic
environmental contamination.
AB - Pesticides are implicated in the decline of honey bee populations. Many
insecticides are neurotoxic and act by different modes of actions. Although a
link between insecticide exposure and changed behaviour has been made, molecular
effects underlying these effects are poorly understood. Here we elucidated
molecular effects at environmental realistic concentrations of two
organophosphates, chlorpyrifos and malathion, the pyrethroid cypermethrin, and
the ryanodine receptor activator, chlorantraniliprole. We assessed
transcriptional alterations of selected genes at three exposure times (24 h, 48
h, 72 h) in caged honey bees exposed to different concentrations of these
compounds. Our targeted gene expression concept focused on several transcripts,
including nicotinic acetylcholine receptor alpha 1 and alpha 2 (nAChRalpha1,
nAChRalpha2) subunits, the multifunctional gene vitellogenin, immune system
related genes of three immune system pathways, genes belonging to the
detoxification system and ER stress genes. Our data indicate a dynamic pattern of
expressional changes at different exposure times. All four insecticides induced
strong alterations in the expression of immune system related genes suggesting
negative implications for honey bee health, as well as cytochrome P450 enzyme
transcripts suggesting an interference with metabolism. Exposure to neurotoxic
chlorpyrifos, malathion and cypermethrin resulted in up-regulation of nAChRalpha1
and nAChRalpha2. Moreover, alterations in the expression of vitellogenin
occurred, which suggests implications on foraging activity. Chlorantraniliprole
induced ER stress which may be related to toxicity. The comparison of all
transcriptional changes indicated that the expression pattern is rather compound
specific and related to its mode of action, but clusters of common
transcriptional changes between different compounds occurred. As transcriptional
alterations occurred at environmental concentrations our data provide a molecular
basis for observed adverse effects of these insecticides to bees.
PMID- 28402839
TI - Borderline personality disorder symptoms and criminal justice system involvement:
The roles of emotion-driven difficulties controlling impulsive behaviors and
physical Aggression.
AB - OBJECTIVE: Borderline personality disorder (BPD) is associated with elevated risk
for a variety of risky behaviors, including criminal behaviors. Yet, limited
research has examined the relation of BPD to criminal justice (CJ) involvement,
or the mechanisms underlying this relation. PROCEDURES: This study examined the
role of two mechanisms, emotion-driven difficulties controlling impulsive
behaviors and physical aggression, in the relation between BPD symptom severity
and CJ involvement among 118 patients in residential substance abuse treatment
(76% male; 62% African-American). Participants completed measures of BPD symptom
severity, CJ contact, diversity of CJ charges, emotion-driven impulse control
difficulties, physical aggression, and covariates (substance use severity and
antisocial personality disorder symptoms). RESULTS: BPD symptom severity was
associated with CJ contact through emotion-driven difficulties controlling
impulsive behaviors, and with diversity of CJ charges through emotion-driven
difficulties controlling impulsive behaviors and physical aggression; however,
the indirect relations to diversity of CJ charges became non-significant when
covariates were included. CONCLUSIONS: Results highlight the important role of
emotion-driven difficulties controlling impulsive behaviors in criminal behaviors
among individuals with BPD symptoms, as well as the potential clinical utility of
targeting this mechanism to prevent CJ involvement and/or recidivism.
PMID- 28402840
TI - High molecular weight components containing N-linked oligosaccharides of Ascaris
suum extract inhibit the dendritic cells activation through DC-SIGN and MR.
AB - Helminths, as well as their secretory/excretory products, induce a tolerogenic
immune microenvironment. High molecular weight components (PI) from Ascaris suum
extract down-modulate the immune response against ovalbumin (OVA). The PI exerts
direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule
and, thus, decreases the T lymphocytes response. Here, we studied the
glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and
MR, in the modulation of DCs activity. Our data showed the presence of
glycoconjugates with high mannose- and complex-type N-linked oligosaccharide
chains and phosphorylcholine residues on PI. In addition, these N-linked
glycoconjugates inhibited the DCs maturation induced by LPS. The binding and
internalization of PI-Alexa were decreased on DCs previously incubated with
mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the
incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished
the down-modulatory effect of PI on these cells. It was also observed that the
blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in
in vitro T cells proliferation. Therefore, our data show the involvement of DC
SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated
components of PI on DCs.
PMID- 28402841
TI - Identification and biochemical characterization of a novel alpha-1,3
mannosyltransferase WfcD from Escherichia coli O141.
AB - Glycosyltransferases (GTs) catalyze the formation of regio- and stereospecific
glycosidic linkages between specific sugar donors and recipients. In this study,
the function of the wfcD gene from the Escherichia coli O141 O-antigen gene
cluster encoding an alpha-1,3-mannosyltransferase that catalyzed the formation of
the linkage Man(alpha1-3)-GlcNAc was biochemically characterized. WfcD was
expressed in E. coli BL21 (DE3), and the enzymatic product was identified by
liquid chromatography-mass spectrometry (LC-MS), collision-induced dissociation
electrospray ionization ion trap multiple tandem MS (CID-ESI-IT-MSn) and
glycosidase digestion using the donor substrate GDP-Man and the synthetic
acceptor substrate decyl diphosphate 2-acetamido-2-deoxy-alpha-D-glucopyranose
(GlcNAc-PP-De). The kinetic and physiochemical properties and the substrate
specificity of WfcD were investigated. WfcD is the first characterized bacterial
mannosyltransferase that acts on the Man(alpha1-3)-GlcNAc linkage. This study
enhances our knowledge of the diverse functions of GTs.
PMID- 28402842
TI - Dendrimer functional hydroxyapatite nanoparticles generated by functionalization
with siloxane-cored PAMAM dendrons.
AB - The surface modification of nano-hydroxyapatite with polyamidoamine (PAMAM)
dendrimer has potential for biomedical applications due to their unique and well
defined secondary structures. This paper presents a facile method to synthesize
siloxane-cored PAMAM dendrons modified Hydroxyapatite nanoparticles. Firstly, the
siloxane-cored PAMAM dendrons with different generations (G1 to G5, respectively)
were synthesized using repetitive reactions between Michael addition and
amidation starting from 3-aminopropyltriethoxysilane. Then, hydroxyapatite
nanoparticles were synthesized by hydrothermal crystallization method and
functionalized with siloxane-cored PAMAM dendrons. These synthesized materials
were characterized by using Fourier-transform infrared spectroscopy (FTIR), X-ray
diffraction (XRD), Scanning electron microscopy (SEM) and Thermogravimetric
analysis (TGA). The results showed that the PAMAM dendrimer functionalization was
carried out successfully and these materials may be applicable in biocomposite
material and/or bone tissue engineering.
PMID- 28402843
TI - Effect of methane-sugar interaction on the solubility of methane in an aqueous
solution.
AB - In this study, the effect of methane-sugar interaction on the solubility of
methane in an aqueous solution at ambient pressure was investigated. Various
sugars, such as fructose, glucose, sucrose, maltose, and raffinose, were used,
and depending on the type and concentration of sugar, the methane solubility
increased from 21.72mg/L (in pure water) to 24.86mg/L. Sugars with a low hydrogen
bonding number between the water and sugar molecules exhibited a large
enhancement in methane solubility. The solute partitioning model and molecular
dynamics simulations were employed to verify the results obtained for the
experimental solubility of methane in aqueous sugar solutions.
PMID- 28402844
TI - A robust, superhydrophobic graphene aerogel as a recyclable sorbent for oils and
organic solvents at various temperatures.
AB - To address oil spillage and organic contaminant problems, the preparation of
efficient sorbent materials is of great importance for global environment and
water source protection. Despite extensive studies, sorbents with both high
efficiency and recyclability are still desired, particularly with the outstanding
sorption performance for different temperature environmental conditions. Herein,
we report a robust reduced graphene aerogel (rGA) as an efficient and recyclable
sorbent for oils and organic solvents, which shows highly efficient absorption of
various oils and organic solvents (up to 19-26 times of its own weight) and
excellent recyclability (>5 times) by heat treatment. Moreover, the absorption
ability of rGA can be maintained over a wide temperature range of -40 degrees C
to 240 degrees C, which can be attributed to the inherent excellent thermal
stability of graphene and goodheat dispersal of three dimensional network
structure. Based on these excellent properties, the rGA is considered to be an
ideal material can be employed for separation and absorption of waste oil and
organic contaminants from the water surface at various temperatures.
PMID- 28402845
TI - Adsorptive removal of antibiotic sulfonamide by UiO-66 and ZIF-67 for wastewater
treatment.
AB - Adsorptive removal of a toxic sulfonamide antibiotic, sulfachloropyradazine
(SCP), from aqueous solution was studied on several metal organic frameworks, UiO
66 and ZIF-67, for the first time. UiO-66 exhibited a much higher adsorption
capacity than ZIF-67, fast kinetics, and easy regeneration for reuse,
demonstrating as a promising adsorbent in wastewater treatment processes. The
batch adsorption shows an adsorption capacity of SCP at 417mg/g on UiO-66. The
kinetic adsorption of SCP on UiO-66 reached equilibrium just in 10min and the
kinetics fits accurately with a pseudo 2nd order model. A plausible mechanism was
proposed based on pH effect, pKa value of the adsorbate and Zeta potential of UiO
66. The high adsorption is mainly contributed to hydrophobicity and pi-pi
interactions along with electrostatic interactions. Thermodynamic studies show
the spontaneous adsorption and exothermic process. The easy regeneration and high
adsorption capacity confirms structural stability of the robust UiO-66 in
wastewater treatment processes, making it suitable for a large scale application.
PMID- 28402846
TI - Structural disjoining pressure induced solid particle removal from solid
substrates using nanofluids.
AB - Nanofluids comprising nanoparticle suspensions in liquids have significant
industrial applications. Prior work performed in our laboratory on the spreading
of a nanofluid on a solid substrate has revealed that the structural disjoining
pressure gradient caused by the layering of the nanoparticles normal to the
confining plane of the film with the wedge profile is a new mechanism for oily
soil detachment from the solid substrate. In the present work, we explore the
application of this new mechanism for the solid particle detachment using latex
particles on glass and a copper-coated wafer substrate using nanofluids. In the
experiment, we employed the nanofluids to observe the detachment of the latex
particles adhered to the glass substrate. We found that the structural disjoining
pressure exerted by the nanoparticles can detach the solid particles on the glass
substrate. A video depicting this mechanism is provided. Our results showed that
the detachment of the particulate solid particles on the solid substrate was
clearly enhanced by the nanofluids, compared to using only pure liquids (such as
water). The detachment efficiency was increased with the increase in the
nanoparticle volume fraction. Our nanofluids also showed a greater detachment
efficiency for the particulate soil removal from the copper-coated wafer
substrates compared to that of pure liquids. We found that the detachment
efficiency is well correlated with the calculated structural disjoining energy.
Our findings in this paper provide new insights for the novel application of the
structural disjoining energy mechanism for cleaning hard surfaces.
PMID- 28402847
TI - IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge.
AB - In concert with their phagocytic activity, macrophages are thought to regulate
the host immunometabolic responses primarily via their ability to produce
specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2
like macrophages secrete IGF1, a hormone previously thought to be exclusively
produced from liver. Ablation of IGF1 receptors from myeloid cells reduced
phagocytosis, increased macrophages in adipose tissue, elevated adiposity,
lowered energy expenditure, and led to insulin resistance in mice fed a high-fat
diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R
knockout (MIKO) mice revealed a reduction in transcripts associated with M2-like
macrophage activation. Furthermore, the MIKO mice infected with helminth
Nippostrongylus brasiliensis displayed delayed resolution from infection with
normal insulin sensitivity. Surprisingly, cold challenge did not trigger an overt
M2-like state and failed to induce tyrosine hydroxylase expression in adipose
tissue macrophages of control or MIKO mice. These results show that IGF1
signaling shapes the macrophage-activation phenotype.
PMID- 28402848
TI - The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus.
AB - Adaptation of influenza A viruses to new hosts are rare events but are the basis
for emergence of new influenza pandemics in the human population. Thus,
understanding the processes involved in such events is critical for anticipating
potential pandemic threats. In 2013, the first case of human infection by an
avian H10N8 virus was reported, yet the H10 hemagglutinin (HA) maintains avian
receptor specificity. However, the 150-loop of H10 HA, as well as related H7 and
H15 subtypes, contains a two-residue insert that can potentially block human
receptor binding. Mutation of the 150-loop on the background of Q226L and G228S
mutations, which arose in the receptor-binding site of human pandemic H2 and H3
viruses, resulted in acquisition of human-type receptor specificity. Crystal
structures of H10 HA mutants with human and avian receptor analogs, receptor
binding studies, and tissue staining experiments illustrate the important role of
the 150-loop in H10 receptor specificity.
PMID- 28402849
TI - Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that
Contribute to Airway Maintenance and Post-injury Repair.
AB - There is evidence that certain club cells (CCs) in the murine airways associated
with neuroepithelial bodies (NEBs) and terminal bronchioles are resistant to the
xenobiotic naphthalene (Nap) and repopulate the airways after Nap injury. The
identity and significance of these progenitors (variant CCs, v-CCs) have remained
elusive. A recent screen for CC markers identified rare Uroplakin3a (Upk3a)
expressing cells (U-CCs) with a v-CC-like distribution. Here, we employ lineage
analysis in the uninjured and chemically injured lungs to investigate the role of
U-CCs as epithelial progenitors. U-CCs proliferate and generate CCs and ciliated
cells in uninjured airways long-term and, like v-CCs, after Nap. U-CCs have a
higher propensity to generate ciliated cells than non-U-CCs. Although U-CCs do
not contribute to alveolar maintenance long-term, they generate alveolar type I
and type II cells after Bleomycin (Bleo)-induced alveolar injury. Finally, we
report that Upk3a+ cells exist in the NEB microenvironment of the human lung and
are aberrantly expanded in conditions associated with neuroendocrine
hyperplasias.
PMID- 28402851
TI - IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6
trans-Signaling.
AB - Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find
that central application of IL-6 in mice suppresses feeding and improves glucose
tolerance. In contrast to leptin, whose action is attenuated in obesity, the
ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses
feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in
hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit
increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans
signaling in the CNS abrogates the ability of IL-6 to suppress feeding.
Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the
hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the
beneficial central IL-6 effects on metabolism. Collectively, these experiments
indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing
IL-6 to exert its beneficial metabolic effects even under conditions of leptin
resistance.
PMID- 28402850
TI - FAD Regulates CRYPTOCHROME Protein Stability and Circadian Clock in Mice.
AB - The circadian clock generates biological rhythms of metabolic and physiological
processes, including the sleep-wake cycle. We previously identified a missense
mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2
(CRY2), a clock protein that causes human advanced sleep phase. This prompted us
to examine the role of FAD as a mediator of the clock and metabolism. FAD
stabilized CRY proteins, leading to increased protein levels. In contrast,
knockdown of Riboflavin kinase (Rfk), an FAD biosynthetic enzyme, enhanced CRY
degradation. RFK protein levels and FAD concentrations oscillate in the nucleus,
suggesting that they are subject to circadian control. Knockdown of Rfk combined
with a riboflavin-deficient diet altered the CRY levels in mouse liver and the
expression profiles of clock and clock-controlled genes (especially those related
to metabolism including glucose homeostasis). We conclude that light-independent
mechanisms of FAD regulate CRY and contribute to proper circadian oscillation of
metabolic genes in mammals.
PMID- 28402852
TI - An Activating STAT3 Mutation Causes Neonatal Diabetes through Premature Induction
of Pancreatic Differentiation.
AB - Activating germline mutations in STAT3 were recently identified as a cause of
neonatal diabetes mellitus associated with beta-cell autoimmunity. We have
investigated the effect of an activating mutation, STAT3K392R, on pancreatic
development using induced pluripotent stem cells (iPSCs) derived from a patient
with neonatal diabetes and pancreatic hypoplasia. Early pancreatic endoderm
differentiated similarly from STAT3K392R and healthy-control cells, but in later
stages, NEUROG3 expression was upregulated prematurely in STAT3K392R cells
together with insulin (INS) and glucagon (GCG). RNA sequencing (RNA-seq) showed
robust NEUROG3 downstream targets upregulation. STAT3 mutation correction with
CRISPR/Cas9 reversed completely the disease phenotype. STAT3K392R-activating
properties were not explained fully by altered DNA-binding affinity or increased
phosphorylation. Instead, reporter assays demonstrated NEUROG3 promoter
activation by STAT3 in pancreatic cells. Furthermore, proteomic and
immunocytochemical analyses revealed increased nuclear translocation of
STAT3K392R. Collectively, our results demonstrate that the STAT3K392R mutation
causes premature endocrine differentiation through direct induction of NEUROG3
expression.
PMID- 28402853
TI - Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage
Specification.
AB - The role of chromatin structure in lineage commitment of multipotent
hematopoietic progenitors (HPCs) is presently unclear. We show here that CD34+
HPCs possess a post-replicative chromatin globally devoid of the repressive
histone mark H3K27me3. This H3K27-unmodified chromatin is required for
recruitment of lineage-determining transcription factors (TFs) C/EBPalpha, PU.1,
and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or
erythroid commitment. Blocking DNA replication or increasing H3K27me3 levels
prevents recruitment of these TFs to DNA and suppresses cytokine-induced
erythroid or myeloid differentiation. However, H3K27me3 is rapidly associated
with nascent DNA in more primitive human and murine HPCs. Treatment of these
cells with instructive cytokines leads to a significant delay in accumulation of
H3K27me3 in nascent chromatin due to activity of the H3K27me3 demethylase UTX.
Thus, HPCs utilize special mechanisms of chromatin modification for recruitment
of specific TFs to DNA during early stages of lineage specification.
PMID- 28402854
TI - In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory
Cells to Hair Cells in Adult Mice.
AB - Hearing loss is widespread and persistent because mature mammalian auditory hair
cells (HCs) are nonregenerative. In mice, the ability to regenerate HCs from
surrounding supporting cells (SCs) declines abruptly after postnatal maturation.
We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts
this age-related decline, leading to conversion of SCs to HCs in mature mouse
cochleae and after noise damage. p27Kip1 deletion, independent of canonical
effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is
lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted
conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted
mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates
auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional
therapeutic targets for ATOH1-mediated HC regeneration.
PMID- 28402855
TI - STIM1 Ca2+ Sensor Control of L-type Ca2+-Channel-Dependent Dendritic Spine
Structural Plasticity and Nuclear Signaling.
AB - Potentiation of synaptic strength relies on postsynaptic Ca2+ signals,
modification of dendritic spine structure, and changes in gene expression. One
Ca2+ signaling pathway supporting these processes routes through L-type Ca2+
channels (LTCC), whose activity is subject to tuning by multiple mechanisms.
Here, we show in hippocampal neurons that LTCC inhibition by the endoplasmic
reticulum (ER) Ca2+ sensor, stromal interaction molecule 1 (STIM1), is engaged by
the neurotransmitter glutamate, resulting in regulation of spine ER structure and
nuclear signaling by the NFATc3 transcription factor. In this mechanism,
depolarization by glutamate activates LTCC Ca2+ influx, releases Ca2+ from the
ER, and consequently drives STIM1 aggregation and an inhibitory interaction with
LTCCs that increases spine ER content but decreases NFATc3 nuclear translocation.
These findings of negative feedback control of LTCC signaling by STIM1 reveal
interplay between Ca2+ influx and release from stores that controls both
postsynaptic structural plasticity and downstream nuclear signaling.
PMID- 28402857
TI - The Retinal Pigment Epithelium Is a Notch Signaling Niche in the Mouse Retina.
AB - Notch signaling in neural progenitor cell is triggered by ligands expressed in
adjacent cells. To identify the sources of active Notch ligands in the mouse
retina, we negatively regulated Notch ligand activity in various neighbors of
retinal progenitor cells (RPCs) by eliminating mindbomb E3 ubiquitin protein
ligase 1 (Mib1). Mib1-deficient retinal cells failed to induce Notch activation
in intra-lineage RPCs, which prematurely differentiated into neurons; however,
Mib1 in post-mitotic retinal ganglion cells was not important. Interestingly,
Mib1 in the retinal pigment epithelium (RPE) also contributed to Notch activation
in adjacent RPCs by supporting the localization of active Notch ligands at RPE
RPC contacts. Combining this RPE-driven Notch signaling and intra-retinal Notch
signaling, we propose a model in which one RPC daughter receives extra Notch
signals from the RPE to become an RPC, whereas its sister cell receives only a
subthreshold level of intra-retinal Notch signal and differentiates into a
neuron.
PMID- 28402856
TI - Chd8 Mutation Leads to Autistic-like Behaviors and Impaired Striatal Circuits.
AB - Autism spectrum disorder (ASD) is a heterogeneous disease, but genetically
defined models can provide an entry point to studying the molecular underpinnings
of this disorder. We generated germline mutant mice with loss-of-function
mutations in Chd8, a de novo mutation strongly associated with ASD, and
demonstrate that these mice display hallmark ASD behaviors, macrocephaly, and
craniofacial abnormalities similar to patient phenotypes. Chd8+/- mice display a
broad, brain-region-specific dysregulation of major regulatory and cellular
processes, most notably histone and chromatin modification, mRNA and protein
processing, Wnt signaling, and cell-cycle regulation. We also find altered
synaptic physiology in medium spiny neurons of the nucleus accumbens.
Perturbation of Chd8 in adult mice recapitulates improved acquired motor learning
behavior found in Chd8+/- animals, suggesting a role for CHD8 in adult striatal
circuits. These results support a mechanism linking chromatin modification to
striatal dysfunction and the molecular pathology of ASD.
PMID- 28402858
TI - Sequential Response to Multiple Developmental Network Circuits Encoded in an
Intronic cis-Regulatory Module of Sea Urchin hox11/13b.
AB - Gene expression in different spatial domains is often controlled by separate cis
regulatory modules (CRMs), but regulatory states determining CRM activity are not
only distinct in space, they also change continuously during developmental time.
Here, we systematically analyzed the regulatory sequences controlling hox11/13b
expression and identified a single CRM required throughout embryonic gut
development. We show that within this CRM, distinct sets of binding sites
recognizing Ets, Tcf, and homeodomain transcription factors control the dynamic
spatial expression of hox11/13b in each developmental phase. Several binding
sites execute multiple, sometimes contradictory, regulatory functions, depending
on the temporal and spatial regulatory context. In addition, we identified a
nearby second CRM operating in inter-modular AND logic with the first CRM to
control hox11/13b expression in hindgut endoderm. Our results suggest a mechanism
for continuous gene expression in response to changing developmental network
functions that depends on sequential combinatorial regulation of individual CRMs.
PMID- 28402859
TI - Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis
through the CXCL13-CXCR5 Pathway.
AB - PKCepsilon, an oncogenic member of the PKC family, is aberrantly overexpressed in
epithelial cancers. To date, little is known about functional interactions of
PKCepsilon with other genetic alterations, as well as the effectors contributing
to its tumorigenic and metastatic phenotype. Here, we demonstrate that PKCepsilon
cooperates with the loss of the tumor suppressor Pten for the development of
prostate cancer in a mouse model. Mechanistic analysis revealed that PKCepsilon
overexpression and Pten loss individually and synergistically upregulate the
production of the chemokine CXCL13, which involves the transcriptional activation
of the CXCL13 gene via the non-canonical nuclear factor kappaB (NF-kappaB)
pathway. Notably, targeted disruption of CXCL13 or its receptor, CXCR5, in
prostate cancer cells impaired their migratory and tumorigenic properties. In
addition to providing evidence for an autonomous vicious cycle driven by
PKCepsilon, our studies identified a compelling rationale for targeting the
CXCL13-CXCR5 axis for prostate cancer treatment.
PMID- 28402860
TI - IDH1 Mutation Promotes Tumorigenesis by Inhibiting JNK Activation and Apoptosis
Induced by Serum Starvation.
AB - Two hallmarks of cancer cells are their resistance to apoptosis and ability to
thrive despite reduced levels of vital serum components. c-jun N-terminal kinase
(JNK) activation is crucial for apoptosis triggered by serum starvation (SS), and
isocitrate dehydrogenase 1 (IDH1) mutations are tumorigenic, in part, because
they produce the abnormal metabolite 2-hydroxyglutarate (2-HG). However, it is
unknown whether 2-HG-induced tumorigenesis is partially due to JNK inhibition and
thus defective SS-induced apoptosis. We show here, using IDH1-R132Q knockin
mutant mouse cells, that 2-HG inhibits JNK activation induced only by SS and not
by UV or doxorubicin, and thus can block apoptosis. Upon SS, Cdc42 normally
disrupts mixed lineage kinase 3's (MLK3's) auto-inhibition, triggering the MLK3
MKK4/7-JNK-Bim apoptotic cascade. 2-HG binds to Cdc42 and abolishes its
association with MLK3, inactivating MLK3 and apoptosis. Allograft tumor assays in
mice demonstrate that this mechanism contributes to tumorigenesis driven by
mutant IDH1, a result confirmed by detection of JNK inactivation in human gliomas
harboring IDH1-R132H mutations.
PMID- 28402861
TI - TRPV1 Regulates Stress Responses through HDAC2.
AB - Stress causes changes in neurotransmission in the brain, thereby influencing
stress-induced behaviors. However, it is unclear how neurotransmission systems
orchestrate stress responses at the molecular and cellular levels. Transient
receptor potential vanilloid 1 (TRPV1), a non-selective cation channel involved
mainly in pain sensation, affects mood and neuroplasticity in the brain, where
its role is poorly understood. Here, we show that Trpv1-deficient (Trpv1-/-) mice
are more stress resilient than control mice after chronic unpredictable stress.
We also found that glucocorticoid receptor (GR)-mediated histone deacetylase 2
(HDAC) 2 expression and activity are reduced in the Trpv1-/- mice and that HDAC2
regulated, cell-cycle- and neuroplasticity-related molecules are altered.
Hippocampal knockdown of TRPV1 had similar effects, and its behavioral effects
were blocked by HDAC2 overexpression. Collectively, our findings indicate that
HDAC2 is a molecular link between TRPV1 activity and stress responses.
PMID- 28402862
TI - Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus.
AB - Drug combinations are synergistic when their combined efficacy exceeds the sum of
the individual actions, but they rarely include ineffective drugs that become
effective only in combination. We identified several "enabling pairs" of
neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose
combination exhibited new functional profiles, including transforming a non
neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of
antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC50 >1 MUM) to
exhibit potent neutralization (IC50 1-10 nM). While FVM09 or m8C4 alone failed to
protect Ebola-virus-infected mice, a combination of the two antibodies provided
100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially
enhanced the potency of two neutralizing antibodies against both Ebola and Sudan
viruses. We identified a hotspot for the binding of these enabling antibody pairs
near the interface of the glycan cap and GP2. Enabling cooperativity may be an
underappreciated phenomenon for viruses, with implications for the design and
development of immunotherapeutics and vaccines.
PMID- 28402863
TI - Biotagging of Specific Cell Populations in Zebrafish Reveals Gene Regulatory
Logic Encoded in the Nuclear Transcriptome.
AB - Interrogation of gene regulatory circuits in complex organisms requires precise
tools for the selection of individual cell types and robust methods for
biochemical profiling of target proteins. We have developed a versatile, tissue
specific binary in vivo biotinylation system in zebrafish termed biotagging that
uses genetically encoded components to biotinylate target proteins, enabling in
depth genome-wide analyses of their molecular interactions. Using tissue-specific
drivers and cell-compartment-specific effector lines, we demonstrate the
specificity of the biotagging toolkit at the biochemical, cellular, and
transcriptional levels. We use biotagging to characterize the in vivo
transcriptional landscape of migratory neural crest and myocardial cells in
different cellular compartments (ribosomes and nucleus). These analyses reveal a
comprehensive network of coding and non-coding RNAs and cis-regulatory modules,
demonstrating that tissue-specific identity is embedded in the nuclear
transcriptomes. By eliminating background inherent to complex embryonic
environments, biotagging allows analyses of molecular interactions at high
resolution.
PMID- 28402864
TI - Meta-analysis on anticoagulation and prevention of thrombosis and mortality among
patients with lung cancer.
AB - BACKGROUND: Venous thromboembolism (Wickham et al., 2012 [1]) is a leading cause
of morbidity and mortality among patients with cancer; however, primary
thromboprophylaxis is not routinely recommended. We performed a systematic review
and meta-analysis of randomized control trials (RCTs) to measure the impact of
primary VTE prevention and its effect on mortality among patients with lung
cancer. METHODS: With assistance from a master librarian, we searched Ovid,
Scopus, DARE, CINAHL, MEDLINE, EMBASE, EBM reviews-Cochrane database of
systematic reviews, EBM reviews-ACP journal, and EBM Reviews-Databases for
relevant studies following the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) guidelines. We included articles addressing the role
of anticoagulation in patients with lung cancer for primary VTE prevention for
outpatients. The clinical outcomes were VTE occurrence, all-cause mortality,
major and clinically relevant non-major bleeding. The results are presented as
odds ratio (OR) and data were analyzed using R and R META package (Version 0.8-2,
Author: Guido Schwarzer). RESULTS: Eleven studies with 5107 patients were
included for the final analysis. We found 50% lower VTE occurrence in the
prophylaxis group with low molecular weight heparin (LMWH) (OR: 0.50; 95%
Confidence Interval (CI): 0.38-0.66; I2: 0%) without an increased bleeding risk
(OR: 2.03; 95% CI: 0.78-5.25; I2: 71.1%). We found a mortality benefit when we
grouped all VTE prevention modalities [LMWH, Warfarin, unfractionated heparin
(UFH)] (OR: 0.75; 95% CI: 0.58-0.96; I2: 18.4%), but no significant difference
when LMWH (OR: 0.74; 95% CI: 0.49-1.11; I2: 56.9%) and warfarin were analyzed
individually (OR: 0.75; 95% CI: 0.47-1.21; I2: 0%). We found higher odds of
bleeding combining all treatment modalities (OR: 3.06; 95% CI: 1.64-5.72; I2:
64.4%) with the greatest occurrence in the warfarin group (OR: 5.42; 95% CI: 3.48
8.45; I2: 45.7%). CONCLUSION: Primary VTE prophylaxis with LMWH reduces the
occurrence of VTE among ambulatory patients with lung cancer, without apparent
increase in bleeding risk. There is a measurable mortality benefit of
anticoagulation strategies that remains elusive when the analysis is restricted
to a single agent.
PMID- 28402866
TI - A randomized trial of aerobic exercise on cognitive control in major depression.
AB - OBJECTIVE: The aim of this study was to examine the effects of an 8-week moderate
intensity aerobic exercise training intervention on cognitive control in
individuals with major depressive disorder (MDD). METHODS: Participants with a
current diagnosis of MDD (n=30; 21.1+/-2.0years) were stratified by depressive
symptoms and randomized to an 8-week intervention of aerobic exercise (AE) or
placebo exercise (PE). AE consisted of three sessions/week of moderate-intensity
exercise training while PE consisted of three sessions/week of light-intensity
stretching. Cognitive control was assessed pre- and post-treatment using
behavioral performance (i.e., reaction time and accuracy) and event-related
potentials (i.e., N2 amplitude). Depressive symptoms and rumination were also
assessed before and after the intervention. RESULTS: Compared with PE, the AE
treatment arm was associated with an increase in N2 amplitude to incongruent
flanker task trials, reflecting an increase in cognitive control processes.
Symptoms of depression also decreased after AE although the treatments did not
differ in their effects on rumination. Exploratory mediation analysis indicated
that changes in N2 amplitude did not mediate pre-to-post treatment reductions in
depressive symptoms. CONCLUSIONS: An 8-week moderate-intensity AE program is
associated with improved neural indices of conflict monitoring and reduced
depressive symptoms among individuals with MDD. SIGNIFICANCE: Future research
examining the influence of exercise in combination with behavioral and
pharmacological treatments for neurocognitive function in MDD is warranted.
PMID- 28402867
TI - Functional connectivity and network analysis during hypoactive delirium and
recovery from anesthesia.
AB - OBJECTIVE: To gain insight in the underlying mechanism of reduced levels of
consciousness due to hypoactive delirium versus recovery from anesthesia, we
studied functional connectivity and network topology using electroencephalography
(EEG). METHODS: EEG recordings were performed in age and sex-matched patients
with hypoactive delirium (n=18), patients recovering from anesthesia (n=20), and
non-delirious control patients (n=20), all after cardiac surgery. Functional and
directed connectivity were studied with phase lag index and directed phase
transfer entropy. Network topology was characterized using the minimum spanning
tree (MST). A random forest classifier was calculated based on all measures to
obtain discriminative ability between the three groups. RESULTS: Non-delirious
control subjects showed a back-to-front information flow, which was lost during
hypoactive delirium (p=0.01) and recovery from anesthesia (p<0.01). The recovery
from anesthesia group had more integrated network in the delta band compared to
non-delirious controls. In contrast, hypoactive delirium showed a less integrated
network in the alpha band. High accuracy for discrimination between hypoactive
delirious patients and controls (86%) and recovery from anesthesia and controls
(95%) were found. Accuracy for discrimination between hypoactive delirium and
recovery from anesthesia was 73%. CONCLUSION: Loss of functional and directed
connectivity were observed in both hypoactive delirium and recovery from
anesthesia, which might be related to the reduced level of consciousness in both
states. These states could be distinguished in topology, which was a less
integrated network during hypoactive delirium. SIGNIFICANCE: Functional and
directed connectivity are similarly disturbed during a reduced level of
consciousness due to hypoactive delirium and sedatives, however topology was
differently affected.
PMID- 28402865
TI - Inhibition versus facilitation of contralesional motor cortices in stroke:
Deriving a model to tailor brain stimulation.
AB - OBJECTIVE: The standard approach to brain stimulation in stroke is based on the
premise that ipsilesional M1 (iM1) is important for motor function of the paretic
upper limb, while contralesional cortices compete with iM1. Therefore, the
approach typically advocates facilitating iM1 and/or inhibiting contralesional M1
(cM1). But, this approach fails to elicit much improvement in severely affected
patients, who on account of extensive damage to ipsilesional pathways, cannot
rely on iM1. These patients are believed to instead rely on the undamaged
cortices, especially the contralesional dorsal premotor cortex (cPMd), for
support of function of the paretic limb. Here, we tested for the first time
whether facilitation of cPMd could improve paretic limb function in severely
affected patients, and if a cut-off could be identified to separate responders to
cPMd from responders to the standard approach to stimulation. METHODS: In a
randomized, sham-controlled crossover study, fifteen patients received the
standard approach of stimulation involving inhibition of cM1 and a new approach
involving facilitation of cPMd using repetitive transcranial magnetic stimulation
(rTMS). Patients also received rTMS to control areas. At baseline, impairment
[Upper Extremity Fugl-Meyer (UEFMPROXIMAL, max=36)] and damage to pathways
[fractional anisotropy (FA)] was measured. We measured changes in time to perform
proximal paretic limb reaching, and neurophysiology using TMS. RESULTS:
Facilitation of cPMd generated more improvement in severely affected patients,
who had experienced greater damage and impairment than a cut-off value of FA
(0.5) and UEFMPROXIMAL (26-28). The standard approach instead generated more
improvement in mildly affected patients. Responders to cPMd showed alleviation of
interhemispheric competition imposed on iM1, while responders to the standard
approach showed gains in ipsilesional excitability in association with
improvement. CONCLUSIONS: A preliminary cut-off level of severity separated
responders for standard approach vs. facilitation of cPMd. SIGNIFICANCE: Cut-offs
identified here could help select candidates for tailored stimulation in future
studies so patients in all ranges of severity could potentially achieve maximum
benefit in function of the paretic upper limb.
PMID- 28402868
TI - Age-related differences in twitch properties and muscle activation of the first
dorsal interosseous.
AB - OBJECTIVE: To examine twitch force potentiation and twitch contraction duration,
as well as electromyographic amplitude (EMGRMS) and motor unit mean firing rates
(MFR) at targeted forces between young and old individuals in the first dorsal
interosseous (FDI). Ultrasonography was used to assess muscle quality. METHODS:
Twenty-two young (YG) (age=22.6+/-2.7years) and 14 older (OD) (age=62.1+/
4.7years) individuals completed conditioning contractions at 10% and 50% maximal
voluntary contraction, (MVC) during which EMGRMS and MFRs were assessed. Evoked
twitches preceded and followed the conditioning contractions. Ultrasound images
were taken to quantify muscle quality (cross-sectional area [CSA] and echo
intensity [EI]). RESULTS: No differences were found between young and old for
CSA, pre-conditioning contraction twitch force, or MFRs (P>0.05). However, OD
individuals exhibited greater EI and contraction duration (P<0.05), and EMGRMS
(YG=35.4+/-8.7%, OD=43.4+/-13.2%; P=0.034). Twitch force potentiation was lower
for OD (0.311+/-0.15N) than YG (0.619+/-0.26N) from pre- to post-50% conditioning
contraction (P<0.001). CONCLUSIONS: Lower levels of potentiation with elongated
contraction durations likely contributed to greater muscle activation during the
conditioning contractions in the OD rather than altered MFRs. Ultrasonography
suggested age-related changes in muscle structure contributed to altered
contractile properties in the OD. SIGNIFICANCE: Greater muscle activation
requirements can have negative implications on fatigue resistance at low to
moderate intensities in older individuals.
PMID- 28402869
TI - The use of composite pulses for improving DEER signal at 94GHz.
AB - The sensitivity of pulsed electron paramagnetic resonance (EPR) measurements on
broad-line paramagnetic centers is often limited by the available excitation
bandwidth. One way to increase excitation bandwidth is through the use of chirp
or composite pulses. However, performance can be limited by cavity or detection
bandwidth, which in commercial systems is typically 100-200MHz. Here we
demonstrate in a 94GHz spectrometer, with >800MHz system bandwidth, an increase
in signal and modulation depth in a 4-pulse DEER experiment through use of
composite rather than rectangular pi pulses. We show that this leads to an
increase in sensitivity by a factor of 3, in line with theoretical predictions,
although gains are more limited in nitroxide-nitroxide DEER measurements.
PMID- 28402870
TI - Long-chain fatty acid feeding frequency in anaerobic codigestion impacts
syntrophic community structure and biokinetics.
AB - This study investigated the impacts of long-chain fatty acid (LCFA) feeding
frequencies on microbial community structure, bioconversion kinetics, and process
stability during anaerobic codigestion. Parallel laboratory-scale anaerobic
codigesters fed with dairy cattle manure were either pulse-fed every two days or
continuously-fed daily, respectively, with oleate (C18:1) in incremental step
increases over 200 days up to 64% of the influent chemical oxygen demand (COD).
The effluent acetate concentration exceeded 3000 mg/L in the continuous-fed
codigester at the highest oleate loading rate, but remained below 100 mg/L in the
pulse-fed codigester at the end of its 48-hr oleate feed cycle. Maximum substrate
conversion rates of oleate (qmax, oleate) and acetate (qmax, acetate) were
significantly higher in the pulse-fed codigester compared to the continuous-fed
codigester. 16S rRNA gene amplicon sequencing showed that Bacteria and Archaea
community profiles diverged based on the codigester LCFA feeding pattern and
loading rate. LCFA-degrading Syntrophomonas bacteria were significantly enriched
in both LCFA codigesters relative to the control digester. The pulse-fed
codigester had the highest community fraction of Syntrophomonas 16S rRNA genes by
the end of the experiment with 43% of Bacteria amplicon sequences. qmax, oleate
and qmax, acetate values were both significantly correlated to absolute
concentrations of Syntrophomonas and Methanosaeta 16S rRNA genes, respectively.
Multiple-linear regression models based on the absolute abundance of
Syntrophomonas and Methanosaeta taxa provided improved predictions of oleate and
acetate bioconversion kinetics, respectively. These results collectively suggest
that pulse feeding rather than continuous feeding LCFA during anaerobic
codigestion selected for higher microbial bioconversion kinetics and functional
stability, which were related to changes in the physiological diversity and
adaptive capacity of syntrophic and methanogenic communities.
PMID- 28402871
TI - Mind the Line Tension: New Criteria for Nanodomains in Biological Membranes.
PMID- 28402872
TI - Forces, Flows, Fluorescence, and MUFluidics.
PMID- 28402873
TI - SAXS-Oriented Ensemble Refinement of Flexible Biomolecules.
AB - The conformational flexibility of a biomolecule may play a crucial role in its
biological function. Small-angle x-ray scattering (SAXS) is a very popular
technique for characterizing biomolecule flexibility. It can be used to determine
a possible structural ensemble of the biomolecule in solution with the aid of a
computer simulation. In this article, we present a tool written in Python, which
iteratively runs multiple independent enhanced sampling simulations such as
amplified collective motions and accelerated molecular dynamics, and an ensemble
optimization method to drive the biomolecule toward an ensemble that fits the
SAXS data well. The tool has been validated with a protein and an RNA system,
i.e., the tandem WW domains of formin-binding protein 21 and the aptamer domain
of SAM-1 riboswitch, respectively. These Python scripts are user-friendly and can
be easily modified if a different simulation engine is preferred.
PMID- 28402874
TI - A Molecular View of the Dynamics of dsDNA Packing Inside Viral Capsids in the
Presence of Ions.
AB - Genome packing in viruses and prokaryotes relies on positively charged ions to
reduce electrostatic repulsions, and induce attractions that can facilitate DNA
condensation. Here we present molecular dynamics simulations spanning several
microseconds of dsDNA packing inside nanometer-sized viral capsids. We use a
detailed molecular model of DNA that accounts for molecular structure,
basepairing, and explicit counterions. The size and shape of the capsids studied
here are based on the 30-nanometer-diameter gene transfer agents of bacterium
Rhodobacter capsulatus that transfer random 4.5-kbp (1.5 MUm) DNA segments
between bacterial cells. Multivalent cations such as spermidine and magnesium
induce attraction between packaged DNA sites that can lead to DNA condensation.
At high concentrations of spermidine, this condensation significantly increases
the shear stresses on the packaged DNA while also reducing the pressure inside
the capsid. These effects result in an increase in the packing velocity and the
total amount of DNA that can be packaged inside the nanometer-sized capsids. In
the simulation results presented here, high concentrations of spermidine3+ did
not produce the premature stalling observed in experiments. However, a small
increase in the heterogeneity of packing velocities was observed in the systems
with magnesium and spermidine ions compared to the system with only salt. The
results presented here indicate that the effect of multivalent cations and of
spermidine, in particular, on the dynamics of DNA packing, increases with
decreasing packing velocities.
PMID- 28402875
TI - Tracking Low-Copy Transcription Factors in Living Bacteria: The Case of the lac
Repressor.
AB - Transcription factors control the expression of genes by binding to specific
sites in DNA and repressing or activating transcription in response to stimuli.
The lac repressor (LacI) is a well characterized transcription factor that
regulates the ability of bacterial cells to uptake and metabolize lactose. Here,
we study the intracellular mobility and spatial distribution of LacI in live
bacteria using photoactivated localization microscopy combined with single
particle tracking. Since we track single LacI molecules in live cells by
stochastically photoactivating and observing fluorescent proteins individually,
there are no limitations on the copy number of the protein under study; as a
result, we were able to study the behavior of LacI in bacterial strains
containing the natural copy numbers (~40 monomers), as well as in strains with
much higher copy numbers due to LacI overexpression. Our results allowed us to
determine the relative abundance of specific, near-specific, and non-specific DNA
binding modes of LacI in vivo, showing that all these modes are operational
inside living cells. Further, we examined the spatial distribution of LacI in
live cells, confirming its specific binding to lac operator regions on the
chromosome; we also showed that mobile LacI molecules explore the bacterial
nucleoid in a way similar to exploration by other DNA-binding proteins. Our work
also provides an example of applying tracking photoactivated localization
microscopy to studies of low-copy-number proteins in living bacteria.
PMID- 28402876
TI - Mechanistic Models Fit to Variable Temperature Calorimetric Data Provide Insights
into Cooperativity.
AB - Allostery pervades macromolecular function and drives cooperative binding of
ligands to macromolecules. To decipher the mechanisms of cooperative ligand
binding it is necessary to define at a microscopic level the structural and
thermodynamic consequences of binding of each ligand to its allosterically
coupled site(s). However, dynamic sampling of alternative conformations
(microstates) in allosteric molecules complicates interpretation of both
structural and thermodynamic data. Isothermal titration calorimetry has the
potential to directly quantify the thermodynamics of allosteric interactions, but
usually falls short of enabling mechanistic insight. This is because 1) its
measurements reflect the sum of overlapping caloric processes involving binding
linked population shifts within and between microstates, and 2) data are
generally fit with phenomenological binding polynomials that are underdetermined.
Nevertheless, temperature-dependent binding data have the potential to resolve
overlapping thermodynamic processes, while mechanistically constrained models
enable hypothesis testing and identification of informative parameters. We
globally fit temperature-dependent isothermal titration calorimetry data for
binding of 11 tryptophan ligands to the homo-undecameric trp RNA-binding
Attenuation Protein from Bacillus stearothermophilus using nearest-neighbor
statistical thermodynamic models. This approach allowed us to distinguish
alternative nearest-neighbor interaction models, and quantifies the thermodynamic
contribution of neighboring ligands to individual binding sites. We also perform
conventional Hill equation modeling and illustrate how comparatively limited it
is in quantitative or mechanistic value. This work illustrates the potential of
mechanistically constrained global fitting of binding data to yield the
microscopic thermodynamic parameters essential for deciphering mechanisms of
cooperativity in a wide range of ligand-regulated homo-oligomeric assemblies.
PMID- 28402877
TI - Structural Basis for the 14-3-3 Protein-Dependent Inhibition of Phosducin
Function.
AB - Phosducin (Pdc) is a conserved phosphoprotein that, when unphosphorylated, binds
with high affinity to the complex of betagamma-subunits of G protein transducin
(Gtbetagamma). The ability of Pdc to bind to Gtbetagamma is inhibited through its
phosphorylation at S54 and S73 within the N-terminal domain (Pdc-ND) followed by
association with the scaffolding protein 14-3-3. However, the molecular basis for
the 14-3-3-dependent inhibition of Pdc binding to Gtbetagamma is unclear. By
using small-angle x-ray scattering, high-resolution NMR spectroscopy, and limited
proteolysis coupled with mass spectrometry, we show that phosphorylated Pdc and
14-3-3 form a complex in which the Pdc-ND region 45-80, which forms a part of
Pdc's Gtbetagamma binding surface and contains both phosphorylation sites, is
restrained within the central channel of the 14-3-3 dimer, with both 14-3-3
binding motifs simultaneously participating in protein association. The N
terminal part of Pdc-ND is likely located outside the central channel of the 14-3
3 dimer, but Pdc residues 20-30, which are also involved in Gtbetagamma binding,
are positioned close to the surface of the 14-3-3 dimer. The C-terminal domain of
Pdc is located outside the central channel and its structure is unaffected by the
complex formation. These results indicate that the 14-3-3 protein-mediated
inhibition of Pdc binding to Gtbetagamma is based on steric occlusion of Pdc's
Gtbetagamma binding surface.
PMID- 28402878
TI - The Role of Evolutionary Selection in the Dynamics of Protein Structure
Evolution.
AB - Homology modeling is a powerful tool for predicting a protein's structure. This
approach is successful because proteins whose sequences are only 30% identical
still adopt the same structure, while structure similarity rapidly deteriorates
beyond the 30% threshold. By studying the divergence of protein structure as
sequence evolves in real proteins and in evolutionary simulations, we show that
this nonlinear sequence-structure relationship emerges as a result of selection
for protein folding stability in divergent evolution. Fitness constraints prevent
the emergence of unstable protein evolutionary intermediates, thereby enforcing
evolutionary paths that preserve protein structure despite broad sequence
divergence. However, on longer timescales, evolution is punctuated by rare events
where the fitness barriers obstructing structure evolution are overcome and
discovery of new structures occurs. We outline biophysical and evolutionary
rationale for broad variation in protein family sizes, prevalence of compact
structures among ancient proteins, and more rapid structure evolution of proteins
with lower packing density.
PMID- 28402879
TI - Fragment-Based NMR Study of the Conformational Dynamics in the bHLH Transcription
Factor Ascl1.
AB - The Achaete-scute homolog 1 (Ascl1) protein regulates a large subset of genes
that leads neuronal progenitor cells to distinctive differentiation pathways
during human brain development. Although it is well known that Ascl1 binds DNA as
a homo- or heterodimer via its basic helix-loop-helix (bHLH) motif, little is
known about the conformational sampling properties of the DNA-free full-length
protein, and in particular about the bHLH domain-flanking N- and C-terminal
segments, which are predicted to be highly disordered in solution. The structural
heterogeneity, low solubility, and high aggregation propensity of Ascl1 in
aqueous buffer solutions make high-resolution studies of this protein a
challenging task. Here, we have adopted a fragment-based strategy that allowed us
to obtain high-quality NMR data providing, to our knowledge, the first
comprehensive high-resolution information on the structural propensities and
conformational dynamics of Ascl1. The emerging picture is that of an overall
extended and highly dynamic polypeptide chain comprising three helical segments
and lacking persistent long-range interactions. We also show that the C-terminal
helix of the bHLH domain is involved in intermolecular interactions, even in the
absence of DNA. Our results contribute to a better understanding of the
mechanisms of action that govern the regulation of proneural transcription
factors.
PMID- 28402880
TI - Sedimentation of Reversibly Interacting Macromolecules with Changes in
Fluorescence Quantum Yield.
AB - Sedimentation velocity analytical ultracentrifugation with fluorescence detection
has emerged as a powerful method for the study of interacting systems of
macromolecules. It combines picomolar sensitivity with high hydrodynamic
resolution, and can be carried out with photoswitchable fluorophores for
multicomponent discrimination, to determine the stoichiometry, affinity, and
shape of macromolecular complexes with dissociation equilibrium constants from
picomolar to micromolar. A popular approach for data interpretation is the
determination of the binding affinity by isotherms of weight-average
sedimentation coefficients sw. A prevailing dogma in sedimentation analysis is
that the weight-average sedimentation coefficient from the transport method
corresponds to the signal- and population-weighted average of all species. We
show that this does not always hold true for systems that exhibit significant
signal changes with complex formation-properties that may be readily encountered
in practice, e.g., from a change in fluorescence quantum yield. Coupled transport
in the reaction boundary of rapidly reversible systems can make significant
contributions to the observed migration in a way that cannot be accounted for in
the standard population-based average. Effective particle theory provides a
simple physical picture for the reaction-coupled migration process. On this
basis, we develop a more general binding model that converges to the well-known
form of sw with constant signals, but can account simultaneously for hydrodynamic
cotransport in the presence of changes in fluorescence quantum yield. We believe
this will be useful when studying interacting systems exhibiting fluorescence
quenching, enhancement, or Forster resonance energy transfer with transport
methods.
PMID- 28402881
TI - Stability and Conformation of a Chemoreceptor HAMP Domain Chimera Correlates with
Signaling Properties.
AB - HAMP domains are dimeric, four-helix bundles that transduce conformational
signals in bacterial receptors. Genetic studies of the Escherichia coli serine
receptor (Tsr) provide an opportunity to understand HAMP conformational behavior
in terms of functional output. To increase its stability, the Tsr HAMP domain was
spliced into a poly-HAMP unit from the Pseudomonas aeruginosa Aer2 receptor.
Within the chimera, the Tsr HAMP undergoes a thermal melting transition at a
temperature much lower than that of the Aer2 HAMP domains. Pulse-dipolar electron
spin resonance spectroscopy and site-specific spin-labeling confirm that the Tsr
HAMP maintains a four-helix bundle. Pulse-dipolar electron spin resonance
spectroscopy was also used to study three well-characterized HAMP mutational
phenotypes: those that cause flagella rotation that is counterclockwise (CCW) A
and kinase-off; CCW B and also kinase-off; and, clockwise (CW) and kinase-on.
Conformational properties of the three HAMP variants support a biphasic model of
dynamic bundle stability, but also indicate distinct conformational changes
within the helix bundle. Functional kinase-on (CW) and kinase-off (CCW A) states
differ by concerted changes in the positions of spin-label sites at the base of
the bundle. Opposite shifts in the subunit separation distances of neighboring
residues at the C-termini of the alpha1 and alpha2 helices are consistent with a
helix scissors motion or a gearbox rotational model of HAMP activation. In the
drastic kinase-off lesion of CCW B, the alpha1 helices unfold and the alpha2
helices form a tight two-helix coiled-coil. The substitution of a critical
residue in the Tsr N-terminal linker or control cable reduces conformational
heterogeneity at the N-terminus of alpha1 but does not affect structure at the C
terminus of alpha2. Overall, the data suggest that transitions from on- to off
states involve decreased motional amplitudes of the Tsr HAMP coupled with helix
rotations and movements toward a two-helix packing mode.
PMID- 28402882
TI - Gating Charge Calculations by Computational Electrophysiology Simulations.
AB - Electrical cell signaling requires adjustment of ion channel, receptor, or
transporter function in response to changes in membrane potential. For the
majority of such membrane proteins, the molecular details of voltage sensing
remain insufficiently understood. Here, we present a molecular dynamics
simulation-based method to determine the underlying charge movement across the
membrane-the gating charge-by measuring electrical capacitor properties of
membrane-embedded proteins. We illustrate the approach by calculating the charge
transfer upon membrane insertion of the HIV gp41 fusion peptide, and validate the
method on two prototypical voltage-dependent proteins, the Kv1.2 K+ channel and
the voltage sensor of the Ciona intestinalis voltage-sensitive phosphatase,
against experimental data. We then use the gating charge analysis to study how
the T1 domain modifies voltage sensing in Kv1.2 channels and to investigate the
voltage dependence of the initial binding of two Na+ ions in Na+-coupled
glutamate transporters. Our simulation approach quantifies various mechanisms of
voltage sensing, enables direct comparison with experiments, and supports
mechanistic interpretation of voltage sensitivity by fractional amino acid
contributions.
PMID- 28402883
TI - A Role of BK Channel in Regulation of Ca2+ Channel in Ventricular Myocytes by
Substrate Stiffness.
AB - Substrate stiffness is crucial for diverse cell functions, but the mechanisms
conferring cells with mechanosensitivity are still elusive. By tailoring
substrate stiffness with 10-fold difference, we showed that L-type voltage-gated
Ca2+ channel current density was greater in chick ventricular myocytes cultured
on the stiff substrate than on the soft substrate. Blockage of the BK channel
increased the Ca2+ current density on the soft substrate and consequently
eliminated substrate stiffness regulation of the Ca2+ channel. The expression of
the BK channel, including the STREX-containing alpha-subunit that forms stretch
activated BK channel in myocytes and the BK channel function in myocytes (and
also in HEK293 cells heterologously expressing STREX-containing alpha- and beta1
subunits) was reduced in cells cultured on the stiff substrate. Furthermore, in
HEK293 cells coexpressing the cardiac CaV1.2 channel and STREX-containing BK
channel, the Ca2+ current density was greater in cells on the stiff substrate,
which was not observed in cells expressing the CaV1.2 channel alone or
coexpressing with the STREX-deleted BK channel. These results provide strong
evidence to show that the stretch-activated BK channel plays a key role in
functional regulation of cardiac voltage-gated Ca2+ channel by substrate
stiffness, revealing, to our knowledge, a novel mechanosensing mechanism in
ventricular myocytes.
PMID- 28402884
TI - Interdigitation between Triglycerides and Lipids Modulates Surface Properties of
Lipid Droplets.
AB - Intracellular lipid droplets (LDs) are the main cellular site of metabolic energy
storage. Their structure is unique inside the cell, with a core of esterified
fatty acids and sterols, mainly triglycerides and sterol esters, surrounded by a
single monolayer of phospholipids. Numerous peripheral proteins, including
several that were previously associated with intracellular compartments
surrounded by a lipid bilayer, have been recently shown to target the surface of
LDs, but how they are able to selectively target this organelle remains largely
unknown. Here, we use atomistic and coarse-grained molecular dynamics simulations
to investigate the molecular properties of the LD surface and to characterize how
it differs from that of a lipid bilayer. Our data suggest that although several
surface properties are remarkably similar between the two structures, key
differences originate from the interdigitation between surface phospholipids and
core neutral lipids that occurs in LDs. This property is extremely sensitive to
membrane undulations, unlike in lipid bilayers, and it strongly affects both
lipid-packing defects and the lateral pressure profile. We observed a marked
change in overall surface properties for surface tensions >10 mN/m, indicative of
a bimodal behavior. Our simulations provide a comprehensive molecular
characterization of the unique surface properties of LDs and suggest how the
molecular properties of the surface lipid monolayer can be modulated by the
underlying neutral lipids.
PMID- 28402885
TI - Line Tension Controls Liquid-Disordered + Liquid-Ordered Domain Size Transition
in Lipid Bilayers.
AB - To better understand animal cell plasma membranes, we studied simplified models,
namely four-component lipid bilayer mixtures. Here we describe the domain size
transition in the region of coexisting liquid-disordered (Ld) + liquid-ordered
(Lo) phases. This transition occurs abruptly in composition space with domains
increasing in size by two orders of magnitude, from tens of nanometers to
microns. We measured the line tension between coexisting Ld and Lo domains close
to the domain size transition for a variety of lipid mixtures, finding that in
every case the transition occurs at a line tension of ~0.3 pN. A computational
model incorporating line tension and dipole repulsion indicated that even small
changes in line tension can result in domains growing in size by several orders
of magnitude, consistent with experimental observations. We find that other
properties of the coexisting Ld and Lo phases do not change significantly in the
vicinity of the abrupt domain size transition.
PMID- 28402886
TI - Three-Dimensional Super-Resolution in Eukaryotic Cells Using the Double-Helix
Point Spread Function.
AB - Single-molecule localization microscopy, typically based on total internal
reflection illumination, has taken our understanding of protein organization and
dynamics in cells beyond the diffraction limit. However, biological systems exist
in a complicated three-dimensional environment, which has required the
development of new techniques, including the double-helix point spread function
(DHPSF), to accurately visualize biological processes. The application of the
DHPSF approach has so far been limited to the study of relatively small
prokaryotic cells. By matching the refractive index of the objective lens
immersion liquid to that of the sample media, we demonstrate DHPSF imaging of up
to 15-MUm-thick whole eukaryotic cell volumes in three to five imaging planes. We
illustrate the capabilities of the DHPSF by exploring large-scale membrane
reorganization in human T cells after receptor triggering, and by using single
particle tracking to image several mammalian proteins, including membrane,
cytoplasmic, and nuclear proteins in T cells and embryonic stem cells.
PMID- 28402887
TI - The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal
Muscle.
AB - Muscle contraction is powered by actin-myosin interaction controlled by Ca2+ via
the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated
with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical
strand that runs along the whole ~1 MUm length of a thin filament. In the absence
of Ca2+, Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in
the blocked, or B, state, where Tpm shields actin from the binding of myosin
heads. Ca2+ binding to Tn releases the Tpm from actin so that it moves
azimuthally around the filament axis to a closed, or C, state, where actin is
partially available for weak binding of myosin heads. Upon transition of the weak
actin-myosin bond into a strong, stereo-specific complex, the myosin heads push
Tpm strand to the open, or O, state allowing myosin binding sites on several
neighboring actin monomers to become open for myosin binding. We used low-angle x
ray diffraction at the European Synchrotron Radiation Facility to check whether
the O- to C-state transition in fully activated fibers of fast skeletal muscle of
the rabbit occurs during transition from isometric contraction to shortening
under low load. No decrease in the intensity of the second actin layer line at
reciprocal radii in the range of 0.15-0.275 nm-1 was observed during shortening
suggesting that an azimuthal Tpm movement from the O- to C-state does not occur,
although during shortening muscle stiffness is reduced compared to the isometric
state, and the intensities of other actin layer lines demonstrate a ~2-fold
decrease in the fraction of myosin heads strongly bound to actin. The data show
that a small fraction of actin-bound myosin heads is sufficient for supporting
the O-state and, therefore the C-state is not occupied in fully activated
skeletal muscle that produces mechanical work at low load.
PMID- 28402888
TI - Influence of Physical Effects on the Swarming Motility of Pseudomonas aeruginosa.
AB - Many species of bacteria can spread over a moist surface via a particular form of
collective motion known as "surface swarming". This form of motility is typically
studied by inoculating bacteria on a gel formed by 0.4-1.5% agar, which contains
essential nutrients for their growth and proliferation. Using Pseudomonas
aeruginosa and its pili-less mutant, DeltaPilA, we investigate physical factors
that either facilitate or restrict the swarming motility, measured by the rate of
increase in area covered by a spreading bacterial colony, i.e., a swarm. The wild
type colony spreads over the agar surface in highly branched structures. The pili
less mutant fills up the area more fully as it spreads, but it also produces
numerous and fragmented branches, or tendrils, at the swarm front. Whereas
additional surfactants enhance swarming, increasing the agar percentage, adding
extra salt or sugar or incorporating viscous agents in the agar matrix all
decrease swarming, supporting the conclusion that swarming motility is restricted
by the surface tension at the swarm front and swarm growth is limited by the rate
of water supply from within the agar gel. The physical basis elaborated through
this study provides a useful framework for understanding the swarming behavior of
numerous species of bacteria.
PMID- 28402889
TI - Unbiased High-Precision Cell Mechanical Measurements with Microconstrictions.
AB - We describe a quantitative, high-precision, high-throughput method for measuring
the mechanical properties of cells in suspension with a microfluidic device, and
for relating cell mechanical responses to protein expression levels. Using a high
speed (750 fps) charge-coupled device camera, we measure the driving pressure
Deltap, maximum cell deformation epsilonmax, and entry time tentry of cells in an
array of microconstrictions. From these measurements, we estimate population
averages of elastic modulus E and fluidity beta (the power-law exponent of the
cell deformation in response to a step change in pressure). We find that cell
elasticity increases with increasing strain epsilonmax according to E ~
epsilonmax, and with increasing pressure according to E ~ Deltap. Variable cell
stress due to driving pressure fluctuations and variable cell strain due to cell
size fluctuations therefore cause significant variability between measurements.
To reduce measurement variability, we use a histogram matching method that
selects and analyzes only those cells from different measurements that have
experienced the same pressure and strain. With this method, we investigate the
influence of measurement parameters on the resulting cell elastic modulus and
fluidity. We find a small but significant softening of cells with increasing time
after cell harvesting. Cells harvested from confluent cultures are softer
compared to cells harvested from subconfluent cultures. Moreover, cell elastic
modulus increases with decreasing concentration of the adhesion-reducing
surfactant pluronic. Lastly, we simultaneously measure cell mechanics and
fluorescence signals of cells that overexpress the GFP-tagged nuclear envelope
protein lamin A. We find a dose-dependent increase in cell elastic modulus and
decrease in cell fluidity with increasing lamin A levels. Together, our findings
demonstrate that histogram matching of pressure, strain, and protein expression
levels greatly reduces the variability between measurements and enables us to
reproducibly detect small differences in cell mechanics.
PMID- 28402890
TI - Cholesterol Regulates Monocyte Rolling through CD44 Distribution.
AB - Cholesterol is an important risk factor of atherosclerosis, due to its active
uptake by monocytes/macrophages. Monocyte recruitment from flowing blood to
atherosclerotic foci is the key first step in the development of atherosclerosis.
Cholesterol content alters cell membrane stiffness, and lateral lipid and protein
diffusion. We hypothesized that cholesterol content will modulate the recruitment
of monocytes to inflamed endothelial surface by altering the dynamics of adhesion
receptors. We depleted or enriched the cellular cholesterol levels using methyl
beta-cyclodextran in freshly isolated human monocytes. We investigated the effect
of these changes on the mechanics of monocyte rolling on E-selectin surfaces at 1
dyn/cm2 in microchannels. Using imaging flow cytometry and atomic force
microscopy, we characterized the distribution of lipid rafts and the E-selectin
counterreceptor CD44 on the monocyte surface. We observed that lower levels of
cholesterol resulted in the uniform, CD44-mediated rolling of monocytes on the E
selectin-coated surfaces. We also observed that cells depleted of cholesterol had
higher membrane fluidity, and more uniform distribution of CD44 counterreceptor,
which resulted in smooth motion of the cells compared to cells enriched with
cholesterol. This work demonstrates that cholesterol can modulate monocyte
adhesion by regulating the receptor mobility, and our results provide insights
into the biophysical regulation of inflammation for the better understanding of
diseases like atherosclerosis and hypercholesterolemia.
PMID- 28402891
TI - Brownian Ratchet Mechanism for Faithful Segregation of Low-Copy-Number Plasmids.
AB - Bacterial plasmids are extrachromosomal DNA that provides selective advantages
for bacterial survival. Plasmid partitioning can be remarkably robust. For high
copy-number plasmids, diffusion ensures that both daughter cells inherit plasmids
after cell division. In contrast, most low-copy-number plasmids need to be
actively partitioned by a conserved tripartite ParA-type system. ParA is an
ATPase that binds to chromosomal DNA; ParB is the stimulator of the ParA ATPase
and specifically binds to the plasmid at a centromere-like site, parS. ParB
stimulation of the ParA ATPase releases ParA from the bacterial chromosome, after
which it takes a long time to reset its DNA-binding affinity. We previously
demonstrated in vitro that the ParA system can exploit this biochemical asymmetry
for directed cargo transport. Multiple ParA-ParB bonds can bridge a parS-coated
cargo to a DNA carpet, and they can work collectively as a Brownian ratchet that
directs persistent cargo movement with a ParA-depletion zone trailing behind. By
extending this model, we suggest that a similar Brownian ratchet mechanism
recapitulates the full range of actively segregated plasmid motilities observed
in vivo. We demonstrate that plasmid motility is tuned as the replenishment rate
of the ParA-depletion zone progressively increases relative to the cargo speed,
evolving from diffusion to pole-to-pole oscillation, local excursions, and,
finally, immobility. When the plasmid replicates, the daughters largely display
motilities similar to that of their mother, except that when the single-focus
progenitor is locally excursive, the daughter foci undergo directed segregation.
We show that directed segregation maximizes the fidelity of plasmid partition.
Given that local excursion and directed segregation are the most commonly
observed modes of plasmid motility in vivo, we suggest that the operation of the
ParA-type partition system has been shaped by evolution for high fidelity of
plasmid segregation.
PMID- 28402893
TI - Magnetic Resonance Relaxation Anisotropy: Physical Principles and Uses in
Microstructure Imaging.
AB - Magnetic resonance imaging (MRI) provides an excellent means of studying tissue
microstructure noninvasively since the microscopic tissue environment is
imprinted on the MRI signal even at macroscopic voxel level. Mesoscopic
variations in magnetic field, created by microstructure, influence the transverse
relaxation time (T2) in an orientation-dependent fashion (T2 is anisotropic).
However, predicting the effects of microstructure upon MRI observables is
challenging and requires theoretical insight. We provide a formalism for
calculating the effects upon T2 of tissue microstructure, using a model of
cylindrical magnetic field perturbers. In a cohort of clinically healthy adults,
we show that the angular information in spin-echo T2 is consistent with this
model. We show that T2 in brain white matter of nondemented volunteers follows a
U-shaped trajectory with age, passing its minimum at an age of ~30 but that this
depends on the particular white matter tract. The anisotropy of T2 also interacts
with age and declines with increasing age. Late-myelinating white matter is more
susceptible to age-related change than early-myelinating white matter, consistent
with the retrogenesis hypothesis. T2 mapping may therefore be incorporated into
microstructural imaging.
PMID- 28402892
TI - Geometric Asymmetry Induces Upper Limit of Mitotic Spindle Size.
AB - Proper organelle size is critical for many cell functions. However, how cells
sense and control their organelle size remains elusive. Here, we develop a
general model to study the size control of mitotic spindles by considering both
extrinsic and intrinsic factors, such as the limited number of building blocks of
the spindle, the interaction between the spindle and cell boundary, the DNA
content, the forces generated by various molecular motors, and the dynamics of
microtubules. We show that multiple pairs of chromatids, two centrosomes, and
microtubules can self-assemble to form a mitotic spindle robustly. We also show
that the boundary-sensing and volume-sensing mechanisms coexist in small cells,
but both break down in large cells. Strikingly, we find that the upper limit of
spindle length naturally arises from the geometric asymmetry of the spindle
structure. Thus, our findings reveal, to our knowledge, a novel intrinsic
mechanism that limits the organelle size.
PMID- 28402894
TI - Reductive dechlorination of carbon tetrachloride by bioreduction of nontronite.
AB - Reductive dechlorination of carbon tetrachloride (CT) was investigated during
bioreduction of iron-containing clay mineral (i.e., nontronite) by iron-reducing
bacteria (Shewanella putrefaciens CN32 (CN32)). In the absence of CT, the
production of Fe(II) significantly increased in nontronite suspension with CN32
in 124 d (11.1% of Fe(III) reduction), resulting in formation of new secondary
Fe(II) mineral phase (i.e., vivianite (FeII3(PO4)2.8H2O)). In the presence of CT,
an acceleration of CT dechlorination was observed after 13 d and it reached
almost 68% of removal efficiency at 32 d in nontronite suspension with CN32,
which was 1.8 times higher than that by CN32 alone (37%). Significant amounts of
formate (30.1%) and CO (2.4%) were measured during the CT dechlorination in the
nontronite suspension with CN32. Results obtained from Fe(II) measurement and X
ray diffraction (XRD) showed the acceleration of Fe(II) production after 13 d and
the formation of vivianite in the range of 13-25 d, suggesting that the biogenic
vivianite enhanced the CT dechlorination in this study. Experimental results from
batch kinetic tests, Fe(II) measurements, XRD analysis, and by-product study
suggested that the formation of vivianite can play a crucial role for the
enhanced reductive dechlorination of CT in phosphorous enriched subsurface
environments with iron-containing clay minerals.
PMID- 28402895
TI - Explosion hazards of LPG-air mixtures in vented enclosure with obstacles.
AB - Numerical simulations were performed to study explosion characteristics of
liquefied petroleum gas (LPG) explosion in enclosure with a vent. Unlike
explosion overpressure and dynamic pressure, explosion temperature of the LPG-air
mixture at a given concentration in a vented enclosure has very little variation
with obstacle numbers for a given blockage ratio. For an enclosure without
obstacle, explosion overpressures for the stoichiometric mixtures and the fuel
lean mixtures reach their maximum within the vent and that for fuel-rich mixture
reaches its maximum beyond and near the vent. Dynamic pressures produced by an
indoor LPG explosion reach their maximum always beyond the vent no matter
obstacles are present or not in the enclosure. A LPG explosion in a vented
enclosure with built-in obstacles is strong enough to make the brick and mortar
wall with a thickness of 370mm damaged. If there is no obstacle in the enclosure,
the lower explosion pressure of several kPa can not break the brick and mortar
wall with a thickness of 370mm. For a LPG explosion produced in an enclosure with
a vent, main hazards, within the vent, are overpressure and high temperature.
However main hazards are dynamic pressure, blast wind, and high temperature
beyond the vent.
PMID- 28402896
TI - Biodegradation of isopropanol and acetone under denitrifying conditions by
Thauera sp. TK001 for nitrate-mediated microbially enhanced oil recovery.
AB - Amendment of reservoir fluid with injected substrates can enhance the growth and
activity of microbes. The present study used isopropyl alcohol (IPA) or acetone
to enhance the indigenous anaerobic nitrate-reducing bacterium Thauera sp. TK001.
The strain was able to grow on IPA or acetone and nitrate. To monitor effects of
strain TK001 on oil recovery, sand-packed columns containing heavy oil were
flooded with minimal medium at atmospheric or high (400psi) pressure. Bioreactors
were then inoculated with 0.5 pore volume (PV) of minimal medium containing
Thauera sp. TK001 with 25mM of acetone or 22.2mM of IPA with or without 80mM
nitrate. Incubation without flow for two weeks and subsequent injection with
minimal medium gave an additional 17.0+/-6.7% of residual oil in place (ROIP)
from low-pressure bioreactors and an additional 18.3% of ROIP from the high
pressure bioreactors. These results indicate that acetone or IPA, which are
commonly used organic solvents, are good substrates for nitrate-mediated
microbial enhanced oil recovery (MEOR), comparable to glucose, acetate or
molasses, tested previously. This technology may be used for coupling
biodegradation of IPA and/or acetone in waste streams to MEOR where these waste
streams are generated in close proximity to an oil field.
PMID- 28402897
TI - Green synthesis of a magnetic hybrid adsorbent (CoFe2O4/NOM): Removal of chromium
from industrial effluent and evaluation of the catalytic potential of recovered
chromium ions.
AB - This work describes the removal of chromium ions from industrial effluent using a
hybrid magnetic adsorbent, CoFe2O4/NOM, synthesized using water rich in natural
organic matter. The hybrid obtained at ambient temperature (HbAmb) was calcined
at 200, 400, and 800 degrees C for 2h, and formation of the cobalt ferrite phase
was confirmed by XRD, which indicated the presence of NOM in the structure of the
material. Removal tests showed that HbAmb provided efficient removal of chromium
at the natural pH of the effluent, while the other materials were effective at pH
6. Evaluation of the kinetics showed excellent performance of the process, with
70-87% removal in 20min, which provided a high degree of flexibility. The hybrid
showed high removal during five reuse cycles, ranging from 96% in the first cycle
to 82% in the final. The matrices containing the saturated adsorbent (HbAmb_Sat)
and recovered chromium ions (CrD) showed high performance in the catalytic
reduction of 4-nitrophenol, with conversion rates of 99.9% in short periods of
time, as well as excellent potential for reuse in three cycles. The results
demonstrated that the production of a technological material and its use for
remediation could be achieved in an ecologically sustainable manner.
PMID- 28402898
TI - Predicting potential release of dissolved organic matter from biochars derived
from agricultural residues using fluorescence and ultraviolet absorbance.
AB - A combination of fluorescence excitation-emission (EEM) spectrophotometry with
parallel factor analysis (PARAFAC) and UV-vis spectroscopy was used to assess
dissolved organic matter (DOM) release by the wheat straw-derived biochar in
various environmental conditions. The results showed that the concentration of
dissolved organic carbon (DOC) extracted from the biochar ranged from 435 to
5000mgkg-1, and the high DOM release would occur under the high temperature and
alkaline environmental conditions. Four humic acid-like substances (C1, C2, C4
and C5), one fulvic acid-like substance (C3) and one tryptophan-like substance
(C6) were identified by PARAFAC model. The distribution of the PARAFAC components
in DOM was distinctively different among various extracts, and mainly composed of
humic acid-like and fulvic acid-like material (accounting 55-78% and 10-37%). The
high temperature enhanced the high release of humic acid-like DOM from the
biochar. Humification index (HIX) of DOM released from the biochar in various
extracts at the temperature of 20 degrees C (0.99-1.09) was lower than that at
the temperature of 60 degrees C (1.31-1.92). The results obtained in the present
study would be beneficial to understand biochar's effects and processes in the
possible environmental applications.
PMID- 28402899
TI - Detection of cyanide ions in aqueous solutions using cost effective colorimetric
sensor.
AB - Cyanide (CN) is one of the most toxic material to the human and environment. It
is very important to develop the diagnostic tools for the detection of CN ions.
Moreover, detection of the ions in an aqueous medium is a challenging task as
water molecules interfere with the sensing mechanism. In this context, we
prepared chemical sensor, S1, having anthraquinone as a signaling unit and
thiourea as a binding site. This sensor exhibited distinct visual color and
spectral changes in response to CN ion over other testing anions in 50% aq. DMSO
solution. However, in 20% aq. DMSO solution, S1 exhibited obvious spectral and
color changes in response to CN, fluoride (F), acetate (Ac) and benzoate (Bz).
Another sensor, S2, having a same signaling unit with that of S1, but a different
binding site of urea group. In contrast to S1, S2 exhibited obvious spectral and
color changes to F in 2.5% aq. DMSO solution. NMR titration results suggested
that the spectral and colorimetric responses were due to the formation of host
guest complex and deprotonation events. Finally, economically viable paper-based
colorimetric "test stripes" of S1 were fabricated to detect the CN ions in 100%
aqueous solution.
PMID- 28402900
TI - Determination of mole fractions of ethyl-cellulose-containing monomers by NMR.
AB - Three samples of ethyl cellulose (EC) with different degrees of substitution (DS)
0.51, 1.41, and 2.28-were prepared by a slurry method using ethyl bromide as the
etherification reagent. 1H-13C HSQC and HSQC-TOCSY NMR spectral analysis allowed
for complete assignment of the 1H and 13C chemical shifts, respectively, of eight
anhydroglucose units (AGUs) comprising EC chains-un-, 2-mono-, 3-mono-, 6-mono-,
2,3-di-, 2,6-di-, 3,6-di-, and 2,3,6-tri-substituted AGUs. In addition, the
lineshape of the quantitative 13C NMR spectra of the three EC samples provided
change in the mole fractions of these AGUs against DS, making it possible to
estimate the reaction mechanism for the production of EC, elucidating
reactivities of the hydroxyl groups at the 2, 3, and 6 positions of cellulose and
interactions between the substituent groups within the same AGU and vicinal AGUs.
PMID- 28402901
TI - A brief screening measure for binge eating in primary care.
AB - OBJECTIVE: Binge eating disorder (BED) is associated with medical and psychiatric
issues commonly seen and managed in primary care; however, the disorder typically
goes undetected as there are no assessment tools feasible for use in primary
care. The objective was to examine the validity of the VA Binge Eating Screener
(VA-BES), a single-item screening measure for binge eating. METHOD: The sample
consisted of 116 veterans referred to a primary care-based weight management
program. Participants had a mean age of 61.66years (SD=8.73) and average BMI of
37.90 (SD=7.35). Frequency of binge eating ranged from zero to 21 episodes per
week. The prevalence of BED was 7.76%. All participants completed the
Questionnaire of Eating and Weight Patterns - Revised (QEWP-R) to assess for BED.
They also completed the VA-BES, and measures of disordered eating and depressive
symptoms. RESULTS: The VA-BES was compared to the QEWP-R to determine the
sensitivity, specificity, positive predictive value, and negative predictive
value for each cutpoint. Analyses revealed one cutpoint (>=2 binge eating
episodes per week) maximized these values, demonstrated excellent agreement with
the QEWP-R (chi2=24.79, p<0.001), and had significant associations with other
variables commonly associated with binge eating. DISCUSSION: This study
demonstrates the utility and validity of a single-item measure to screen for
binge eating in primary care. The item can quickly and easily identify binge
eating, thus facilitating referral to treatment and potentially subsequent
improvements in related medical and mental health comorbidities treated in
primary care.
PMID- 28402902
TI - Cardiovascular outcome studies with incretin-based therapies: Comparison between
DPP-4 inhibitors and GLP-1 receptor agonists.
AB - Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor
agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies
used for the treatment of type 2 diabetes. Non-inferiority versus placebo was
shown in large prospective cardiovascular outcome trials in patients with high
cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS
(sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6
(semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP
4is were non confirmed as no cardiovascular protection could be evidenced.
However, LEADER showed a significant reduction in major cardiovascular events,
myocardial infarction, cardiovascular and all-cause mortality in patients treated
by liraglutide compared to placebo. These positive results contrasted with the
non-inferiority results with lixisenatide in ELIXA. They were partially confirmed
with semaglutide in SUSTAIN 6 despite the absence of reduction in cardiovascular
mortality. Hospitalisation for heart failure was not increased except with
saxagliptin in SAVOR-TIMI 53. The reasons for different outcomes between trials
remain largely unknown as well as the precise underlying mechanisms explaining
the cardiovascular protection by liraglutide. The clinical relevance of results
with DPP-4is and GLP-1RAs is discussed. Ongoing trials with linagliptin and
several once-weekly GLP-1RAs should provide new insights into remaining
fundamental questions.
PMID- 28402903
TI - Nutritional anti-inflammatories in the treatment and prevention of type 2
diabetes mellitus and the metabolic syndrome.
AB - AIMS: Obesity-fuelled metabolic syndrome and diabetes is now a global epidemic.
There is increasing evidence that these and other chronic conditions have common
inflammatory antecedents. There is an interest in nutritionally based anti
inflammatory treatments for type 2 diabetes and metabolic syndrome. The aim of
this review is to examine the evidence from a 5-year period; 2011-2016, for
nutritionally based anti-inflammatory treatments for the Metabolic Syndrome and
Type 2 Diabetes Mellitus. METHODS: A literature search produced a total number of
1377 records, of which 26 papers were evaluated. RESULTS: Literature was analysed
and tabulated according to date, outcome measures and results. CONCLUSION: The
evidence is strong for use of polyphenolic compounds, fish oils and vitamins in
reducing inflammation biomarkers, however the impact on metabolic control is less
evident.
PMID- 28402904
TI - Longitudinal relations between adolescents' self-esteem and prosocial behavior
toward strangers, friends and family.
AB - The present study examined age-trends and longitudinal bidirectional relations in
self-esteem and prosocial behavior toward strangers, friends, and family over a
four-year time period (age 11 to 14). A total of 681 adolescents were recruited
in the United States (51% girls, 28% single parent families). A longitudinal
panel model was conducted and the results showed that adolescent self-esteem was
associated longitudinally with subsequent prosocial behavior toward strangers,
and earlier prosocial behavior toward strangers promoted subsequent self-esteem.
There were no such bidirectional relations between self-esteem and prosocial
behavior toward friends and family. Findings also highlight the complexity of
adolescent development of selfesteem and the multidimensional nature of prosocial
behavior. Discussion focuses on understanding the dynamic interplay between
adolescent selfesteem and prosocial behavior.
PMID- 28402905
TI - Acceptable health and priority weighting: Discussing a reference-level approach
using sufficientarian reasoning.
AB - Health care systems are challenged in allocating scarce health care resources,
which are typically insufficient to fulfil all health care wants and needs. One
criterion for priority setting may be the 'acceptable health' approach, which
suggests that society may want to assign higher priority to health benefits in
people with "unacceptable" than in people with "acceptable" health. A level of
acceptable health then serves as a reference point for priority setting.
Empirical research has indicated that people may be able and willing to define
health states as "unacceptable" or "acceptable", but little attention has been
given to the normative implications of evaluating health benefits in relation to
a reference level of acceptable health. The current paper aims to address this
gap by relating insights from the distributive justice literature, i.e. the
sufficientarian literature, to the acceptable health approach, as we argue that
these approaches are related. We specifically focus on the implications of an
'acceptability' approach for priority weighting of health benefits, derived from
sufficientarian reasoning and debates, and assess the moral implications of such
weighting.
PMID- 28402906
TI - Applying fermentation liquid of food waste as carbon source to a pilot-scale
anoxic/oxic-membrane bioreactor for enhancing nitrogen removal: Microbial
communities and membrane fouling behaviour.
AB - Fermentation liquid of food waste (FLFW) was applied as an external carbon source
in a pilot-scale anoxic/oxic-membrane bioreactor (A/O-MBR) system to enhance
nitrogen removal for treating low COD/TN ratio domestic wastewater. Results
showed that, with the FLFW addition, total nitrogen removal increased from lower
than 20% to 44-67% during the 150days of operation. The bacterial metabolic
activities were obviously enhanced, and the significant change in microbial
community structure promoted pollutants removal and favored membrane fouling
mitigation. By monitoring transmembrane pressure and characterizing typical
membrane foulants, such as extracellular polymeric substances (EPS), dissolved
organic matter (DOM), and inorganics and biopolymers in the cake layer, it was
confirmed that FLFW addition did not bring about any additional accumulation of
membrane foulants, acceleration of fouling rate, or obvious irreversible membrane
fouling in the whole operation period. Therefore, FLFW is a promising alternative
carbon source to enhance nitrogen removal for the A/O-MBR system.
PMID- 28402907
TI - Strategies for enhanced deammonification performance and reduced nitrous oxide
emissions.
AB - Deammonification's performance and associated nitrous oxide emissions (N2O)
depend on operational conditions. While studies have investigated factors for
high performances and low emissions separately, this study investigated
optimizing deammonification performance while simultaneously reducing N2O
emissions. Using a design of experiment (DoE) method, two models were developed
for the prediction of the nitrogen removal rate and N2O emissions during single
stage deammonification considering three operational factors (i.e., pH value,
feeding and aeration strategy). The emission factor varied between 0.7+/-0.5% and
4.1+/-1.2% at different DoE-conditions. The nitrogen removal rate was predicted
to be maximized at settings of pH 7.46, intermittent feeding and aeration.
Conversely, emissions were predicted to be minimized at the design edges at pH
7.80, single feeding, and continuous aeration. Results suggested a weak positive
correlation between the nitrogen removal rate and N2O emissions, thus, a single
optimizing operational set-point for maximized performance and minimized
emissions did not exist.
PMID- 28402908
TI - Current treatment trends and the need for better predictive tools in the
management of ductal carcinoma in situ of the breast.
AB - Ductal carcinoma in situ (DCIS) of the breast represents a group of heterogeneous
non-invasive lesions the incidence of which has risen dramatically since the
advent of mammography screening. In this review we summarise current treatment
trends and up-to-date results from clinical trials studying surgery and adjuvant
therapy alternatives, including the recent consensus on excision margin width and
its role in decision-making for post-excision radiotherapy. The main challenge in
the clinical management of DCIS continues to be the tailoring of treatment to
individual risk, in order to avoid the over-treatment of low-risk lesions or
under-treatment of DCIS with higher risk of recurring or progressing into
invasion. While studies estimate that only about 40% of DCIS would become
invasive if untreated, heterogeneity and complex natural history have prevented
adequate identification of these higher-risk lesions. Here we discuss attempts to
develop prognostic tools for the risk stratification of DCIS lesions and their
limitations. Early results of a UK-wide audit of DCIS management (the Sloane
Project) have also demonstrated a lack of consistency in treatment. In this
review we offer up-to-date perspectives on current treatment and prediction of
DCIS, highlighting the pressing clinical need for better prognostic indices.
Tools integrating both clinical and histopathological factors together with
molecular biomarkers may hold potential for adequate stratification of DCIS
according to risk. This could help develop standardised practices for optimal
management of patients with DCIS, improving clinical outcomes while providing
only the amount of therapy required for each individual patient.
PMID- 28402909
TI - Seedless synthesis of nanocomposites, optical properties, and effects of
additives on their surface resonance plasmon bands.
AB - The work describes an easy seedless competitive chemical reduction method for the
synthesis of Ag@Au/Ag bimetallic nanoparticles by mixing AgNO3, HAuCl4 and
cysteine. Transmission electron microscope (TEM) images show that the large
number of irregular, cross-linking, and aggregated Ag@Au/Ag are formed in a
reaction mixture (HAuCl4+AgNO3+cysteine), whereas flower-like nanocomposites are
obtained in presence of cetyltrimethylammonium bromide (CTAB), which acted as a
shape-directing agent. Optical images reveal that the initially reaction proceeds
through formation of purple color, which changes into dark brown color with the
reaction time, indicating the formation of Ag@Au/Ag nanocomposites. The Ag+ has
strong tendency to form complex with cysteine. Firstly, the reduction of Ag+ ions
to Ag0 occurred by the HS group of the cysteine-Ag complex. Secondly, AuCl4- ions
adsorbed on the positive surface of Ag0, which undergoes reduction by potential
deposition, and leads to the formation of Ag@Au/Ag bimetallic nanoparticles.
Inorganic electrolytes (NaCl, NaBr, NaNO3 and Na2SO4) have significant impact on
the stability and aggregation of Ag@Au/Ag nanocomposites.
PMID- 28402910
TI - Skin-nipple-sparing mastectomy: The first approach in primary myxoid
chondrosarcoma of the breast.
AB - The primary mammary chondrosarcoma corresponds to less than 0,5% of the mammary
malignancies. For the period ranging from 1967 to 2014, only 18 cases were
reported in the literature. A 41year old woman found a hard nodule on her
external right superior quadrant/axillary prolongation through breast self
examination. The vacuum-assisted core biopsy (VACB) revealed "high grade extra
skeletal myxoid chondrosarcoma". A skin-nipple-sparing mastectomy with the
insertion of a mammary expander was performed. A protocol of adjuvant
radiotherapy was also indicated. Until 2013, the gold standard was the radical
mastectomy. By 2014, there were two cases of conservative approach to
quadrantectomy. To our knowledge, this represents the first case in the
literature in which a skin-nipple-sparing mastectomy has been performed on a
primitive mesenchymal neoplasm of the breast. Such an oncoplastic approach was
performed considering the young age of the woman, to assure the surgical
radicality and a better quality of life to the patient.
PMID- 28402911
TI - Hassab's operation for Joubert syndrome with congenital hepatic fibrosis: A case
report.
AB - INTRODUCTION: Joubert syndrome is characterized by psychomotor developmental
delay, hypotonia, oculomotor abnormalities, occasional retinal dystrophy and
cystic kidneys, and frequent and often, striking breathing abnormalities,
especially in the neonatal period, with panting tachypnea followed by apnea. We
report a case of Joubert syndrome with hepatic fibrosis, portal hypertension, and
pancytopenia treated by Hassab's operation. PRESENTATION OF CASE: Our patient was
a 27-year-old woman with a history of tachypnea, muscle hypotonia, and
psychomotor retardation shortly after birth and a diagnosis of Joubert syndrome
at 2 years of age. At 19 years of age, she was diagnosed with progressive
pancytopenia. At 27 years of age, she visited her local doctor for sudden-onset
hematemesis. Endoscopy revealed esophageal varices exhibiting the red color sign
and no evidence of recent bleeding. Splenomegaly and development of portal
collateral circulation were observed on computed tomography scans. The patient
was referred to our hospital, where she was diagnosed with Joubert syndrome and
hepatic fibrosis, portal hypertension, and hypersplenism. After performing
Hassab's operation, the pancytopenia improved, but anticoagulant therapy was
required for splenic vein thrombosis. The patient was discharged on postoperative
day 25. Two years following surgery, the gastroesophageal varices were
controlled, and no progression of the splenic vein thrombosis or hepatic failure
was evident. CONCLUSION: This is the first case report of Hassab's operation for
congenital hepatic fibrosis in a patient with Joubert syndrome, a rare congenital
condition. We achieved a favorable clinical outcome.
PMID- 28402912
TI - Changes in growth and physiological parameters of spring barley and common radish
under the influence of 1-butyl-2,3-dimethylimidazolium tetrafluoroborate.
AB - Ionic liquids (ILs) constitute a large group of chemical substances, which,
thanks to their desirable properties, still attract attention of scientists and
representatives of the industry. This may lead to a greater commercial use of
these compounds, which will undoubtedly lead to the contamination of soils,
constituting the basis of plant vegetation, with these substances. This paper
presents effect of 1-butyl-2,3-dimethylimidazolium tetrafluoroborate [BMMIM][BF4]
on the growth and development of spring barley and common radish and on the
physiological and biochemical changes in these plants. The used IL was
characterized by relatively high toxicity for the monocotyledonous plant, which
was exhibited by shortening of the plant length and their root length, decreasing
the fresh weight yield. Moreover, [BMMIM][BF4] led to the decrease in the content
of all photosynthetic pigments in spring barley seedlings, reflecting the
decrease in the fresh yield. Furthermore, the increase of malondialdehyde (MDA)
level and changes in contents of hydrogen peroxide (H2O2) and the activity of
antioxidant enzymes, that is, superoxide dismutase (SOD), catalase (CAT), and
peroxidase (POD) may suggest the occurrence of oxidative stress in spring barley.
The decrease in the content of photosynthetic pigment and the increase of POD
activity constitute the most reliable markers of oxidative stress and, at the
same time, the signs of early aging of spring barley plants. Common radish was
the plant with a very high tolerance for the used IL, which can be indicated by,
that is, EC50 values, determined based on inhibition of root length, plant
length, and fresh weight yield.
PMID- 28402913
TI - The impacts of decision uncertainty on municipal solid waste management.
AB - Municipal solid waste treatment options are not necessarily pragmatic if the
stakeholders in the system don't mutually agree on their shares of liabilities.
Stakeholders will select an option if their benefits are maximized and costs are
minimized. A decision support framework is required to assess various waste
treatment options and predict the optimal decision, considering multiple criteria
and conflicting preferences of multiple stakeholders. Because of the inherent
complexity, uncertainty is unavoidable and should be acknowledged to enhance the
reliability in the decision-making process. Uncertainties in the cost and benefit
estimates, and stakeholders' ability in verbalizing their preferences and their
knowledge about each other's priorities can impact the outcome of such
environmental management problem. In this study, uncertainty assessment methods
such as sensitivity analysis, fuzzy Analytical Hierarchy Process, and Bayesian
games have been explored. A case study in Vancouver (BC, Canada) has been used as
a proof of concept.
PMID- 28402914
TI - Potential interaction between transport and stream networks over the lowland
rivers in Eastern India.
AB - Extension of transport networks supports good accessibility and associated with
the development of a region. However, transport lines have fragmented the
regional landscape and disturbed the natural interplay between rivers and their
floodplains. Spatial analysis using multiple buffers provides information about
the potential interaction between road and stream networks and their impact on
channel morphology of a small watershed in the Lower Gangetic Plain. Present
study is tried to understand the lateral and longitudinal disconnection in
headwater stream by rural roads with the integration of geoinformatics and field
survey. Significant (p < 0.001) growth of total road length and number of road
stream crossing in the last five decades (1970s-2010s) contribute to making
longitudinal and lateral disconnection in the fluvial system of Kunur River
Basin. Channel geometry from ten road-stream crossings shows significant (p =
0.01) differences between upstream and downstream of crossing structure and
created problems like downstream scouring, increased drop height at outlet,
formation of stable bars, severe bank erosion, and make barriers for river biota.
The hydro-geomorphic processes are also adversely affected due to lateral
disconnection and input of fine to coarse sediments from the river side growth of
unpaved road (1922%). Limited streamside development, delineation of stream
corridor, regular monitoring and engineering efficiency for the construction of
road and road-stream crossing might be effective in managing river geomorphology
and riverine landscape.
PMID- 28402915
TI - Removal of chromium (VI) from water using nanoscale zerovalent iron particles
supported on herb-residue biochar.
AB - A composite material consisting of nanoscale zerovalent iron particles supported
on herb-residue biochar (nZVI/BC) was synthesized and used for treatment of
Cr(VI)-contaminated water. The effects of initial pH, chromium concentration,
contact time, and competition with coexisting anions and natural organic matter
(NOM) were also investigated. nZVI/BC was characterized by X-ray diffraction
(XRD), transmission electron microscopy (TEM), and scanning electron microscopy
analysis (SEM), and the Brunauer-Emmett-Teller surface area was measured. TEM and
X-ray photoelectron spectroscopy (XPS) analysis before and after reaction with
Cr(VI) showed that reduction and coprecipitation occurred during hexavalent
chromium adsorption. The removal of Cr(VI) was highly pH-dependent and the
adsorption kinetics data agreed well with the pseudo-second-order model. The
presence of SO42- and humic acid promoted Cr(VI) removal at both low and high
concentrations, while the HCO3- inhibited the reaction. These results prove that
nZVI/BC can be an effective reagent for removal of Cr(VI) from solutions.
PMID- 28402916
TI - Potential of chopped heath biomass and spent growth media to replace wood chips
as bulking agent for composting high N-containing residues.
AB - We investigated the potential of C-rich byproducts to replace wood chips as
bulking agent (BA) during composting. The impact of these alternatives on the
composting process and on compost stability and characteristics was assessed.
Three BA (chopped heath biomass and spent growth media used in strawberry and
tomato cultivation) were used for processing leek residues in windrow composting.
All BA resulted in stable composts with an organic matter (OM) content suitable
for use as soil amendment. Using chopped heath biomass led to high pile
temperatures and OM degradation and a nutrient-poor compost with high C/P ratio
appropriate for increasing soil organic carbon content in P-rich soils. Spent
substrates can replace wood chips, however, due to their dense structure and
lower biodegradation potential, adding a more coarse BA is required. Generally,
the nutrient content of the composts with growth media was higher than the
composts with wood chips and chopped heath biomass.
PMID- 28402917
TI - Towards the integration of orbital space use in Life Cycle Impact Assessment.
AB - A rising sustainability concern is occurring in the space sector: 29,000 human
made objects, larger than 10cm are orbiting the Earth but only 6% are operational
spacecrafts. Today, space debris is today a significant and constant danger to
all space missions. Consequently, it becomes compelled to design new space
missions considering End-of-Life requirements in order to ensure the sustainable
use of space orbits. Furthermore, Life Cycle Assessment (LCA) has been identified
by the European Space Agency as an adequate tool to measure the environmental
impact of spacecraft missions. Hence, our challenge is to integrate orbital space
use into Life Cycle Impact Assessment (LCIA) to broaden the scope of LCA for
space systems. The generation of debris in the near-Earth's orbital regions leads
to a decrease in volume availability. The Area-of-Protection (AoP) 'resources'
seems to be the most relevant reflection of this depletion. To address orbital
space use in a comprehensive way, we propose a first attempt at establishing an
impact pathway linking outer space use to resources. This framework will be the
basis for defining new indicator(s) related to orbital space use.
PMID- 28402918
TI - Improvement of wheat straw anaerobic digestion through alkali pre-treatment:
Carbohydrates bioavailability evaluation and economic feasibility.
AB - Lignocellulosic biomasses such as wheat straw are widely used as a feedstock for
biogas production. However, these biomasses are mainly composed of a compact
fibre structure and therefore, it is recommended to treat them prior to its usage
for biogas production in order to improve their bioavailability. The aim of this
work is to evaluate, in terms of performance stability, methane yield and
economic feasibility, two different scenarios: a mesophilic codigestion of wheat
straw and animal manure with or without a low-energy demand alkaline pre
treatment (0.08gKOHgTS-1of wheat straw, for 24h and at 25 degrees C). Besides
this, said pre-treatment was also analysed based on the improvement of the
bioavailable carbohydrate content in the untreated versus the pre-treated wheat
straw. The results pointed out that pre-treated wheat straw prompted a more
stable performance (in terms of pH and alkalinity) and an improved methane yield
(128% increment) of the mesophilic codigestion process, in comparison to the
"untreated" scenario. The pre-treatment increased the content of cellulose,
hemicellulose and other compounds (waxes, pectin, oil, etc.) in the liquid
fraction, from 5% to 60%, from 11.5% to 39.1% TS and from 57% to 79% of the TS in
the liquid fraction for the untreated and pre-treated wheat straws, respectively.
Finally, the pre-treated scenario gained an energy surplus of a factor 13.5 and
achieved a positive net benefit of 90.4?tVS-WS-1d-1, being a favourable case for
an eventual scale-up of the combined process.
PMID- 28402919
TI - Inhibition of miR-363 protects cardiomyocytes against hypoxia-induced apoptosis
through regulation of Notch signaling.
AB - Cardiomyocyte apoptosis contributes to the pathological process of ischemic heart
diseases, such as myocardial infarction. Emerging evidence suggests that
microRNAs (miRNAs) play critical roles in the pathological process of myocardial
infarction by regulating cardiomyocyte apoptosis. Previous studies have reported
that miR-363 is an apoptosis-related miRNA. However, whether miR-363 is involved
in regulating cardiomyocyte apoptosis remains unclear. This study aimed to
investigate the potential role of miR-363 in the regulation of hypoxia-induced
cardiomyocyte apoptosis. We found that miR-363 expression was significantly
increased in hypoxic cardiomyocytes and that inhibition of miR-363 effectively
protected cardiomyocytes against hypoxia-induced apoptosis. Bioinformatics
analysis predicted that Notch1 is a potential target gene of miR-363. This
finding was validated by dual-luciferase reporter assay, real-time quantitative
polymerase chain reaction, and Western blot analysis. miR-363 inhibition
significantly promoted the activation of Notch signaling in hypoxic
cardiomyocytes. However, knockdown of Notch1 markedly reversed the protective
effects induced by miR-363 inhibition. Furthermore, blocking the Notch signaling
also significantly abrogated the protective effects of miR-363 inhibition.
Overall, these findings suggest that inhibition of miR-363 protects
cardiomyocytes against hypoxia-induced apoptosis through promotion of Notch1
expression and activation of Notch signaling. Our study provides a novel
understanding of the molecular basis of hypoxia-induced cardiomyocyte apoptosis
and suggests a potential therapeutic target for myocardial infarction.
PMID- 28402920
TI - miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest
and targeting P21.
AB - Esophageal squamous cancer is one of the most fatal malignancies and often suffer
recurrence after radiotherapy. Downregulation of miRNA-200c is associated with
radiotolerance. We aim to investigate the role of miRNA-200c in radiosensitivity
and develop a systemic treatment strategy for esophageal squamous cancer.
Overexpression of miRNA-200c by transfection was determined by RT-PCR.
Radiosensitizing effect of miRNA-200c on esophageal squamous cancer cells was
determined by clonogenic assay and xenograft model. Cell cycle was analyzed by
flow cytometry. The levels of Cyclin B1, cyclin D1, cyclin E1, CDK2, CDK4, Cdc2
and P21 protein expressions were detected by western blotting. The results of our
study revealed that miRNA-200c enhanced the radiosensitivity significantly in
esophageal squamous cancer cell line in vitro and in vivo. miRNA-200c induced
G2/M and sub-G1 phase arrest and reduced S phase rate of the irradiated Eca-109
cells and downregulated expression levels of Cyclin B1, cdc2 and upregulated P21
expression level. Present results demonstrate that downregulation of miRNA-200c
is associated with radiotolerance. miRNA-200c increases radiosensitivity by G2/M
and sub-G1 phase arrest through modulating Cyclin B1, cdc2 and P21 expression
levels.
PMID- 28402921
TI - MiR-155 promotes cell proliferation and inhibits apoptosis by PTEN signaling
pathway in the psoriasis.
AB - MicroRNAs (miRNAs) have been demonstrated to contribute to malignant progression
in psoriasis development. The purposes of the study was to evaluated the effects
of miRNA-155 on cell proliferation, migration and apoptosis in psoriasis
development via PTEN singaling pathway and identify its direct target protein.
Quantitative real-time RT-PCR (qRT-PCR) was performed to examine the level of miR
155 in psoriasis cells, miR-155 was downregulated in a psoriasis cell line Hacat
by transfected with small interfering RNA (siRNA), respectively. Cell survival
was detected by the MTT assay and colony formation assay. Cell migration and
invasion were measured via wound-healing assayand transwell assay. In addition,
cell cycle and apoptosis about psoriasis cells was measured by flow cytometry. In
this study, qRT-PCR assay showed that the expressions of miR-155 mRNA in
psoriasis tissues were significantly higher than that in normal tissues. The
assays about cell growth and proliferation showed that miR-155 knockdown led to a
significant decrease in cell proliferation which was determined by MTT assay and
colony formation assay compared to those of Lv-NC cells. Flow cytometry analysis
showed that depletion of miR-155 could cause cell cycle change and the number of
apoptotic cells was significantly increased in Lv-miR155 cells compared with
control cells. In addition, the expression of several apoptosis-related factors
were dramatically changed, such as PTEN, PIP3, AKT, p-AKT, Bax and Bcl-2. Our
findings indicate that down-regulation of miR-155 significantly inhibits
proliferation, migration, invasion and promotes apoptosis through PTEN singaling
pathway in psoriasis cells. miR-155 might function as an oncogene miRNA in the
progress of psoriasis.
PMID- 28402922
TI - Toxicity of triptolide and the molecular mechanisms involved.
AB - Triptolide (TP), a major active and toxic ingredient isolated from the
traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF). A widespread
application of TP raises the question on the safety of its use in clinical
settings. The metabolism of TP is mediated by hepatic cytochrome P450s, and a
strong correlation exists between TP toxicity and CPY3A. Toxicity of TP and the
molecular mechanisms of its toxic effects have been studied in recent years.
Studies have demonstrated that TP exposure results in injury of various organs,
including the liver, kidney, testes, ovary, and heart in animals and even in
humans, according to clinical case reports. Moreover, on the cellular level, TP
has been reported to be associated with diverse toxic effects, encompassing
membrane damage, mitochondrial disruption, metabolism dysfunction, endoplasmic
reticulum stress, oxidative stress, apoptosis and autophagy. This review presents
an overview of the current findings related to TP toxicity with an emphasis on
biological targets and the molecular mechanisms that may be involved, thus
providing a systematic understanding of the mechanisms by which TP affects cells
and tissues in vitro and in vivo.
PMID- 28402923
TI - Effect of the treatment with Euterpe oleracea Mart. oil in rats with Triton
induced dyslipidemia.
AB - OBJECTIVES: Dyslipidemias are defined as changes in lipid metabolism that have
abnormal concentrations of lipids or lipoproteins in the bloodstream. Chronic
increase in triglyceride and low-density lipoprotein (LDL-c) levels are known as
risk factors for the atherogenesis process as well as other cardiovascular
diseases (CVDs). The magnitude of the problems caused by dyslipidemias impels
research by new agents that act in the prevention and control. Thus, products
from the Amazonian biodiversity, such as Euterpe oleracea oil (OFEO), rich in
unsaturated fatty acids (UFAs), constitutes a study source for the treatment of
alterations in lipid metabolism. METHODS: The present study aims to investigate
the effect of OFEO treatment in rats with Triton-induced dyslipidemia (Tyloxapol
WR1339). RESULTS: The physicochemical and chromatographic results confirmed the
chemical composition of OFEO with a predominance of UFAs (67.83%), with Oleic
acid being the majority (54.32%). At Triton-induced dyslipidemia, the animals
treated with OFEO and Simvastatin showed a significant reduction in total
cholesterol levels, with values of 121.7+/-29.5 (p<0.01) and 96.6+/-17.6mg/dL
(p<0.001), respectively. OFEO also significantly reduced LDL-c levels (p<0.01)
and triglycerides (p<0.001). OFEO and Simvastatin improved the lipid profile by
significantly increasing (p<0.05) the high-density lipoprotein (HDL) values.
CONCLUSIONS: Therefore, it is concluded that the OFEO treatment used in the
conditions of this study had a beneficial effect on dyslipidemia, acting as
antihypercholesterolemic and antihypertriglyceridemic, thus possibly contributing
as a preventive agent for CVDs.
PMID- 28402924
TI - Remote tele-mentored ultrasound for non-physician learners using FaceTime: A
feasibility study in a low-income country.
AB - PURPOSE: Ultrasound (US) is a burgeoning diagnostic tool and is often the only
available imaging modality in low- and middle-income countries (LMICs). However,
bedside providers often lack training to acquire or interpret US images. We
conducted a study to determine if a remote tele-intensivist could mentor
geographically removed LMIC providers to obtain quality and clinically useful US
images. MATERIALS AND METHODS: Nine Haitian non-physician health care workers
received a 20-minute training on basic US techniques. A volunteer was connected
to an intensivist located in the USA via FaceTime. The intensivist remotely
instructed the non-physicians to ultrasound five anatomic sites. The tele
intensivist evaluated the image quality and clinical utility of performing tele
ultrasound in a LMIC. RESULTS: The intensivist agreed (defined as "agree" or
"strongly agree" on a five-point Likert scale) that 90% (57/63) of the FaceTime
images were high quality. The intensivist felt comfortable making clinical
decisions using FaceTime images 89% (56/63) of the time. CONCLUSIONS: Non
physicians can feasibly obtain high-quality and clinically relevant US images
using video chat software in LMICs. Commercially available software can connect
providers in institutions in LMICs to geographically removed intensivists at a
relatively low cost and without the need for extensive training of local
providers.
PMID- 28402925
TI - Time delays associated with vasoactive medication preparation and delivery in
simulated patients at risk of cardiac arrest.
AB - PURPOSE: To compare, quantify, and describe the time-delays associated with four
common methods of adrenaline administration in the simulated setting of impending
cardiac arrest. METHODS: Using sham medication and a high-fidelity simulator,
experienced Nurses prepared, then delivered, adrenaline by: i) bolus, ii) lower
concentration infusion iii) higher-concentration infusion, and iv) higher
concentration infusion plus carrier-line. We recorded medication preparation and
delivery time, plus administration errors and self-reported competence. RESULTS:
Median total delay was i) 120s for bolus (95% CI 112-128s); ii) 179s for lower
concentration infusion (95% CI 172-186s); iii) 296s for higher concentration
infusion (95% CI 285-307s); and iv) 411s for higher concentration infusion plus
carrier line (95% CI 399-423s). Time to prepare/deliver a bolus was less than any
infusion (p<0.001). Time to prepare/deliver a lower-concentration infusion was
less than either higher-concentration infusion (p<0.001). No substantial
equipment failures or medication errors were observed. Participants reported high
competence. The majority of delay was from drug preparation not delivery.
CONCLUSIONS: We highlight potentially dangerous delays with administration of
life-saving medications by all four methods. We should prioritize boluses, and
focus on improving drug preparation times and human performance, more than drug
delivery and equipment.
PMID- 28402927
TI - Hepatitis C Virus, Inflammation, and Cellular Aging: Turning Back Time.
AB - There is evidence that hepatitis C virus (HCV) infection, like HIV infection, may
be associated with chronic inflammation, immune activation, and immune
senescence, which contribute to increased risks for cardiometabolic or other
diseases outside the liver, as well as to ongoing damage in the liver. These
effects may persist after a sustained virologic response (SVR) is achieved with
HCV therapy. Such findings support initiation of treatment for HCV-infected
individuals before damage to the liver is apparent and monitoring of individuals
for complications even after an SVR is achieved. Fibrosis is not always
reversible after SVR is achieved, and this should serve as an argument against
waiting until fibrosis develops before initiating treatment for HCV-infected
individuals. This article summarizes a presentation by Susanna Naggie, MD, MHS,
at the IAS-USA continuing education program, Management of Hepatitis C Virus in
the New Era: Small Molecules Bring Big Changes, in New York, New York, in
September 2015.
PMID- 28402926
TI - Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2
mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.
AB - Although curcumin shows anti-proliferative and anti-inflammatory activities in
various cancers, the effect of curcumin on cellular migration in endometrial
adenocarcinoma cells remains to be understood. The current investigation was
aimed to explore the anti-proliferative and anti-migratory effects of curcumin
and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo
experimental studies showed that curcumin inhibited the proliferation of
endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft
mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells.
Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed
by scratch wound assay. In transwell migration studies, knock down of Slit-2
reversed the anti-migratory effect of curcumin in these cell lines. Curcumin
significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and
primary endometrial cancer cells while it down-regulated the expression of
stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the
expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the
migration of endometrial cancer cells. In summary, we have demonstrated that
curcumin has inhibitory effect on cellular migration via Slit-2 mediated down
regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These
findings helped explore the role of Slit-2 in endometrial cancer cells.
PMID- 28402928
TI - Management of Advanced Fibrosis in the Context of Hepatitis C Virus Infection.
AB - Advanced fibrosis may be present in a substantial proportion of individuals with
asymptomatic, chronic hepatitis C virus (HCV) infection, including those who have
been newly diagnosed. HCV treatment improves all-cause and liver-related
mortality in individuals with advanced fibrosis, and there is some evidence that
reversal of decompensated liver disease may occur in those with a sustained
virologic response. HCV treatment is also crucial for individuals undergoing
liver transplantation, as recurrent HCV infection posttransplantation is
associated with accelerated fibrosis progression and increased risk of poor
outcomes. This article summarizes a presentation by Elizabeth C. Verna, MD, at
the IAS-USA continuing education program, Management of Hepatitis C Virus in the
New Era: Small Molecules Bring Big Changes, held in New York, New York, in
September 2015.
PMID- 28402929
TI - Kidney Disease and HIV Infection.
AB - The risk of acute and chronic kidney disease remains higher in HIV-infected
persons than in the general population, and kidney disease in HIV-infected
persons is associated with poor outcomes, including increased mortality. HIV
associated nephropathy occurs less frequently in the era of antiretroviral
therapy. HIV immune complex kidney disease is being diagnosed more frequently,
but the term is currently used to refer to a heterogeneous group of kidney
diseases. Comorbid chronic kidney disease poses a growing burden in HIV-infected
persons due to an overrepresentation of risk factors such as black race,
diabetes, hypertension, and coinfection with hepatitis C virus. Drug-induced
kidney toxicity also remains a concern. This article summarizes a presentation by
Christina M. Wyatt, MD, at the Ryan White HIV/AIDS Program Clinical Care
Conference held in New Orleans, Louisiana, in December 2015.
PMID- 28402930
TI - HIV Treatment and Prevention: An Overview of Recommendations From the IAS-USA
Antiretroviral Guidelines Panel.
AB - Updated recommendations from the IAS-USA Antiretroviral Guidelines Panel on
antiretroviral therapy for the treatment and prevention of HIV infection in
adults were published in the Journal of the American Medical Association in 2016.
The updated, evidence-based recommendations address when to initiate
antiretroviral therapy, recommended initial antiretroviral regimens, including
integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens
for persons in whom an InSTI is not an option, and special treatment
considerations. The interface between antiretroviral therapy and opportunistic
infections, when and how to switch antiretroviral therapy, laboratory monitoring,
engagement in care, adherence to antiretroviral therapy, and use of
antiretroviral therapy as HIV prevention are also discussed, as well as future
directions in HIV treatment. This article summarizes an IAS-USA continuing
education webinar presented by Paul A. Volberding, MD, in August 2016.
PMID- 28402931
TI - HABP2 p.G534E variant in patients with family history of thyroid and breast
cancer.
AB - Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary
predisposition cancer syndrome associated with mutations in candidate genes
including HABP2. Two of 20 probands from families with history of PTC and breast
carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2
p.G534E. Sanger sequencing was used to confirm the involvement of this variant in
three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister
(with no malignant tumor so far) from F1 were homozygous for the variant whereas
one relative with PTC from F2 was negative for the variant. Although the proband
of the F3 with PTC was HABP2 wild type, three relatives presented the variant.
Five of 170 healthy Brazilian individuals with no family history of BC or PTC and
three of 50 sporadic PTC presented the p.G534E. These findings suggested no
association of this variant with our familial PTC cases. Genes potentially
associated with deregulation of the extracellular matrix organization pathway
(CTSB, TNXB, COL4A3, COL16A1, COL24A1, COL5A2, NID1, LOXL2, MMP11, TRIM24 and
MUSK) and DNA repair function (NBN and MSH2) were detected by WES, suggesting
that other cancer-associated genes have pathogenic effects in the risk of
familial PTC development.
PMID- 28402932
TI - The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel
resistance of lung adenocarcinoma A549 cells.
AB - Long non-coding RNAs (lncRNAs) are a family of non-protein-coding RNAs that might
affect Lung adenocarcinoma (LAD) chemo-resistance and most of them could be used
as biomarkers and therapy targets. However, the potential function of lncRNA
ANRIL contributed paclitaxel chemo-resistance in LAD is still unknown. This study
aimed to observe the expression of ANRIL in LAD, evaluate its biological role in
the resistance of LAD cells to paclitaxel and explore the apoptosis role in the
ANRIL associated mechanism. Our results showed that ANRIL functioning as a
potential oncogene was up-regulated in LAD, and promoted the acquisition of chemo
resistance in paclitaxel partly through the mitochondrial pathway by modulating
the expression of apoptosis-related protein cleaved-PARP and Bcl-2. These
findings might improve LAD patients' paclitaxel treatment and made ANRIL to be a
new target for paclitaxel-based chemotherapy in LAD.
PMID- 28402933
TI - PDK1 inhibitor GSK2334470 exerts antitumor activity in multiple myeloma and forms
a novel multitargeted combination with dual mTORC1/C2 inhibitor PP242.
AB - A deeper understanding of the complex pathogenesis of multiple myeloma (MM)
continues to lead to novel therapeutic approaches. Prior studies suggest that 3
phosphoinositide-dependent kinase 1 (PDK1) is expressed and active, acting as a
crucial regulator of molecules that are essential for myelomagenesis. In the
present study, we show that GSK2334470 (GSK-470), a novel and highly specific
inhibitor of PDK1, induces potent cytotoxicity in MM cell lines including
Dexamethasone-resistant cell line, but not in human normal cells. Insulin-like
growth factor-1 could not rescue GSK-470-induced cell death. Moreover, GSK-470
down-modulates phosphor-PDK1, thereby inhibiting downstream phosphor-AKT at
Thr308 and mTOR complex 1 (mTORC1) activity. However, GSK-470 could not affect
mTORC2 activity and phosphor-AKT at Ser473. RPMI 8226 and OPM-2 cells with low
expression of PTEN show relative resistant to GSK-470. Knockout of PTEN by shRNA
resulted in a partial reversion of GSK-470-mediated growth inhibition, whereas
overexpression of PTEN enhanced myeloma cell sensitivity to GSK-470, suggesting
that the sensitivity to GSK-470 is correlated with PTEN expression statue in MM
cells. Combining PP242, a dual mTORC1/C2 inhibitor, with GSK-470, had greater
antimyeloma activity than either one alone in vitro and in MM xenograft model
established in immunodeficient mice. In particular, this combination was able to
result in a complete inhibition of mTORC1/C2 and full activity of AKT. Together,
these findings raise the possibility that combining PDK1 antagonist GSK-470 with
mTORC1/C2 inhibitors may represent a novel strategy against MM including drug
resistant myeloma, regardless of PTEN expression status.
PMID- 28402934
TI - Anti-cancer activity of Annexin V in murine melanoma model by suppressing tumor
angiogenesis.
AB - Annexin V, a protein with high affinity to phosphatidylserine (PS) in a calcium
dependent manner, has been widely used to probe apoptosis. Annexin V in
inhibiting engulfment of apoptotic cells by macrophages had been reported to
increase the immunogenicity of tumor cells undergoing apoptosis. However, far
less is known about its multiple properties, especially in cancer therapies. Here
we found that Annexin V had a good anti-tumor activity in murine
melanomaxenograft model. Treatment with Annexin V showed significant reduction in
tumor size and remarkable tumor necrosis areas. The serum level of VEGF was
downregualted by Annexin V both in normal mice and mice bearing tumor, suggesting
that its new role on impeding tumor angiogenesis. In Silico analysis using
Oncomine database, we also found the negative correlation of AnnexinV and VEGF
both in skin and melanoma. The decreased Annexin V expression shows linearity
relation with the elevated VEGF expression. These data provided a possibility
that Annexin V can be used as a novel angiogenesis inhibitor in tumor therapy.
PMID- 28402935
TI - MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing.
AB - Deregulation of miRNAs has been observed virtually in all major types of cancer,
whereas the miRNA signature in GIST is not well characterized yet. In this study
the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal
tissue samples was performed using small RNA-seq approach and differentially
expressed miRNAs as well as isomiRNAs were defined. Highly significantly
deregulated miRNAs were selected for validation by Taq-Man low-density array in
replication group of 40 paired samples. Validated miRNAs were further subjected
to enrichment analysis, which revealed significantly enriched KEGG pathways in
the main GIST associated pathways. Further, we used an integrated analysis of
miRNA-mRNA correlations for KIT and PDGFRA target genes and found a significant
correlation between all of the enriched miRNAs and their target gene KIT. Results
of the phenotype analysis showed miR-509-3p to be up-regulated in epithelioid and
mixed cell types compared to spindle type, whereas miR-215-5p showed negative
correlation with risk grade of GIST. These data reveal a detailed miRNA profile
of GIST and highlight new candidates that may be important in the development of
malignant disease.
PMID- 28402936
TI - Lysophosphatidic acid (LPA) as a pro-fibrotic and pro-oncogenic factor: a pivotal
target to improve the radiotherapy therapeutic index.
AB - Radiation-induced fibrosis is widely considered as a common but forsaken
phenomenon that can lead to clinical sequela and possibly vital impairments.
Lysophosphatidic acid is a bioactive lipid involved in fibrosis and probably in
radiation-induced fibrosis as suggested in recent studies. Lysophosphatidic acid
is also a well-described pro-oncogenic factor, involved in carcinogenesis
processes (proliferation, survival, angiogenesis, invasion, migration). The
present review highlights and summarizes the links between lysophosphatidic acid
and radiation-induced fibrosis, lysophosphatidic acid and radioresistance, and
proposes lysophosphatidic acid as a potential central actor of the radiotherapy
therapeutic index. Besides, we hypothesize that following radiotherapy, the newly
formed tumour micro-environment, with increased extracellular matrix and
increased lysophosphatidic acid levels, is a favourable ground to metastasis
development. Lysophosphatidic acid could therefore be an exciting therapeutic
target, minimizing radio-toxicities and radio-resistance effects.
PMID- 28402937
TI - Breaking the crosstalk of the cellular tumorigenic network: Hypothesis for
addressing resistances to targeted therapies in advanced NSCLC.
AB - In the light of current treatment developments for non-small cell lung cancer
(NSCLC), the idea of a plastic cellular tumorigenic network bound by key
paracrine signaling pathways mediating resistances to targeted therapies is
brought forward. Based on a review of available preclinical and clinical data in
NSCLC combinational approaches to address drivers of this network with marketed
drugs are discussed. Five criteria for selecting drug combination regimens aiming
at its disruption and thereby overcoming resistances are postulated.
PMID- 28402938
TI - Cathepsins in digestive cancers.
AB - Cathepsins are lysosomal peptidases belonging to the papain family, and based on
their catalytic sites, these enzymes can be divided into serine, cysteine and
aspartic proteases. The studies conducted to date have identified, 15 types of
cathepsins that are widely distributed in intracellular and extracellular spaces.
These proteases participate in various pathological activities, including the
occurrence and development of human cancers. Several recent studies suggest that
cathepsins, particularly cathepsins B, D, E and L, contribute to digestive
tumorigenesis. Cathepsins were found to promote the development of most digestive
cancers except liver cancer, in which they might have the opposite effects. Due
to their important roles in digestive tumors, cathepsins might be therapeutic
targets for the treatment of digestive cancers.
PMID- 28402939
TI - Distinct functions of dynamin isoforms in tumorigenesis and their potential as
therapeutic targets in cancer.
AB - Dynamins and their related proteins participate in the regulation of
neurotransmission, antigen presentation, receptor internalization, growth factor
signalling, nutrient uptake, and pathogen infection. Recently, emerging findings
have shown dynamin proteins can also contribute to the genesis of cancer. This up
to-date review herein focuses on the functionality of dynamin in cancer
development. Dynamin 1 and 2 both enhance cancer cell proliferation, tumor
invasion and metastasis, whereas dynamin 3 has tumor suppression role. Antisense
RNAs encoded on the DNA strand opposite a dynamin gene regulate the function of
dynamin, and manipulate oncogenes and tumor suppressor genes. Certain dynamin
related proteins are also upregulated in distinct cancer conditions, resulting in
apoptotic resistance, cell migration and poor prognosis. Altogether, dynamins are
potential biomarkers as well as representing promising novel therapeutic targets
for cancer treatment. This study also summarizes the current available dynamin
targeted therapeutics and suggests the potential strategy based on signalling
pathways involved, providing important information to aid the future development
of novel cancer therapeutics by targeting these dynamin family members.
PMID- 28402940
TI - Prognostic role of microRNAs in human gastrointestinal cancer: A systematic
review and meta-analysis.
AB - BACKGROUND: Gastrointestinal cancers (GICs) mainly including esophageal, gastric
and colorectal cancer, are the most common cause of cancer-related death and lead
into high mortality worldwide. We performed this systematic review and meta
analysis to elucidate relationship between multiple microRNAs (miRs) expression
and survival of GIC patients. METHODS: We searched a wide range of database.
Fixed-effects and random-effects models were used to calculate the pooled hazard
ratio values of overall survival and disease free survival. In addition, funnel
plots were used to qualitatively analyze the publication bias and verified by
Begg's test while it seems asymmetry. RESULTS: 60 studies involving a total of
6225 patients (1271 with esophageal cancer, 3467 with gastric cancer and 1517
with colorectal cancer) were included in our meta-analysis. The pooled hazard
ratio values of overall survival related to different miRs expression in
esophageal, gastric, colorectal and gastrointestinal cancer were 2.10 (1.78
2.49), 2.02 (1.83-2.23), 2.54 (2.14-3.02) and 2.15 (1.99-2.31), respectively. We
have identified a total of 59 miRs including 23 significantly up-regulated
expression miRs (miR-214, miR-17, miR-20a, miR-200c, miR-107, miR-27a, etc.) and
36 significantly down-regulated expression miRs (miR-433, let-7g, miR-125a-5p,
miR-760, miR-206, miR-26a, miR-200b, miR-185, etc.) correlated with poor
prognosis in GIC patients. Moreover, 35 of them revealed mechanisms. CONCLUSION:
Overall, specific miRs are significantly associated with the prognosis of GIC
patients and potentially eligible for the prediction of patients survival. It
also provides a potential value for clinical decision-making development and may
serve as a promising miR-based target therapy waiting for further elucidation.
PMID- 28402942
TI - Mesenchymal stem cells and their therapeutic applications in inflammatory bowel
disease.
AB - Mesenchymal stem or stromal cells (MSCs) are non-hematopoietic stem cells that
facilitate tissue regeneration through mechanisms involving self-renewal and
differentiation, supporting angiogenesis and tissue cell survival, and limiting
inflammation. MSCs were originally identified and expanded in long-term cultures
of cells from bone marrow and other organs; and their native identity was
recently confined into pericytes and adventitial cells in vascularized tissue.
The multipotency, as well as the trophic and immunosuppressive effects, of MSCs
have prompted the rapid development of clinical applications for many diseases
involving tissue inflammation and immune disorders, including inflammatory bowel
disease. Although standard criteria have been established to define MSCs, their
therapeutic efficacy has varied significantly among studies due to their natural
heterogenicity. Thus, understanding the biological and immunological features of
MSCs is critical to standardize and optimize MSCs-based therapy. In this review,
we highlight the cellular and molecular mechanisms involved in MSCs-mediated
tissue repair and immunosuppression. We also provide an update on the current
development of MSCs-based clinical trials, with a detailed discussion of MSC
based cell therapy in inflammatory bowel disease.
PMID- 28402943
TI - Expression of wild-type p53-induced phosphatase 1 in diabetic epiretinal
membranes.
AB - OBJECTIVE: The aims of the present study were to investigate the expression and
distribution of Wild-type p53-induced phosphatase 1 (Wip1) in diabetic patients
with proliferative diabetic retinopathy (PDR) with epiretinal membranes (ERMs)
meanwhile analyze the colocalization of Wip1 and nuclear factor kappa-B (NF
kappaB) p65 in ERMs. METHODS: ERMs samples were collected from patients with PDR
(PDR group) or non-diabetic patients with idiopathic epiretinal membranes (iERMs)
(control group) during pars plana vitrectomy. Real-Time PCR analysis was carried
out to examine the mRNA expression of Wip1 in ERMs. Immunohistochemical analysis
and Immunofluorescent analysis were performed to detect the protein expression of
Wip1 in ERMs. Double immunofluorescent staining was performed to detect the
colocalization of Wip1 and glial fibrillary acidic protein (GFAP) (retinal glial
cells marker), also Wip1 and NF-kappaB. RESULTS: ERMs were obtained from 17 eyes
of 17 patients with PDR (the PDR group) and 9 eyes of 9 nondiabetic patients (the
control group) with iERMs. Our results showed high expression levels of Wip1
mRNAs in ERMs after PDR, but low in iERMs. In addition, both immunohistochemistry
and immunofluorescence assay showed strong immunoreactivity for Wip1 in PDR ERMs.
Furthermore, Wip1 and GFAP were coexpressed in PDR membranes. Finally, the
expression of Wip1 was paralleled with NF-kappaB. CONCLUSION: These data support
the notion that Wip1 contributes to the formation of the ERMs in PDR membranes
via NF-kappaB signaling.
PMID- 28402946
TI - DLC1: a tumor suppressor that regulates Rho signaling.
PMID- 28402944
TI - Exosome: emerging biomarker in breast cancer.
AB - Exosomes are nano-sized membrane vesicles released by a variety of cell types,
and are thought to play important roles in intercellular communications. In
breast cancer, through horizontal transfer of various bioactive molecules, such
as proteins and mRNAs, exosomes are emerging as local and systemic cell-to-cell
mediators of oncogenic information and play an important role on cancer
progression. This review outlines the current knowledge and concepts concerning
the exosomes involvement in breast cancer pathogenesis (including tumor
initiation, invasion and metastasis, angiogenesis, immune system modulation and
tumor microenvironment) and cancer therapy resistance. Moreover, the potential
use of exosomes as promising diagnostic and therapeutic biomarkers in breast
cancer are also discussed.
PMID- 28402945
TI - A prospective, open-label, multicenter, observational study to evaluate the
efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for
autologous stem cell transplantation-ineligible patients with multiple myeloma.
AB - Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first
line treatment for transplantation-ineligible multiple myeloma (MM). This study
investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM
patients received 9 cycles of VMP in this prospective, multicenter, observational
study. The primary endpoint was 2-year progression-free survival (PFS).Thirty
nine (22%) patients were aged >= 75 years and 83 (47.4%) patients had
International Staging System stage III. A median of 5 cycles were delivered.
Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%.
With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS
and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was
not reached. PFS was significantly different depending on performance status
(Eastern Cooperative Oncology Group < 2 vs. >= 2; p = 0.0002), beta2
microglobulin level (< 5.5 vs. >= 5.5 mg/L; p = 0.0481), and cumulative dose of
bortezomib (< 35.1 vs. >= 35.1 mg/m2; p < 0001). The common adverse events (AEs)
were in line with the well-known toxicity profiles associated with VMP.In
conclusion, VMP is a feasible and effective front-line treatment for transplant
ineligible older patients with MM in Korea. Continuing therapy with prompt
adjustment of treatment according to AEs may be important to improve outcomes of
elderly patients.
PMID- 28402947
TI - Overexpression of the transcription factor ATF3 with a regulatory molecular
signature associates with the pathogenic development of colorectal cancer.
AB - The identification of novel biomarkers of cancer is important for improved
diagnosis and prognosis. With an abundant amount of resources in the publicly
available database, such as the Cancer Genome Atlas (TCGA) database, an
integrative strategy is used to systematically characterize the aberrant patterns
of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation
sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular
signatures. The expression of the transcription factor ATF3 was elevated in human
CRC specimens in a TMA by immunochemistry analysis compared to the adjacent
normal tissues. In addition, ATF3 overexpression associated with a regulatory
molecular signature, and its functions are related to the pathogenic development
of CRC. Furthermore, putative ATF3 regulatory elements were identified within the
promoters of ATF3 target genes and were confirmed by ChIP-Seq. Critically, in
higher ATF3 expression cell lines (HCT116 and RKO) with CRISPR/Cas9 mediated ATF3
knock out, we are able to show that ATF3 target genes such as CEACAM1, DUSP14,
HDC, HLF and ULBP2, are required for invasion and proliferation, and they are
robustly linked with poor prognosis in CRC. Our findings have important
implications for CRC tumorigenesis and may be exploited for diagnostic and
therapeutic purposes.
PMID- 28402948
TI - C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the
treatment of brain glioma.
AB - Chemotherapy of brain glioma faces a major obstacle owing to the inability of
drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in
brain glioma site result in a rapid infiltration, making complete surgical
removal virtually impossible. Herein, we reported a novel kind of C-type
natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring
drug across the BBB, and for treating brain glioma along with disrupting
neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro
and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified
vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the
brain glioma, and destroy neovasculatures effectively. The above mechanisms could
be associated with the following aspects, namely, long circulation in the blood;
drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated
transcytosis; elimination of brain glioma cells and disruption of neovasculatures
by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid
vesicles could induce apoptosis of the glioma cells. The mechanisms could be
related to the activations of caspase 8, caspase 3, p53, and reactive oxygen
species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles
could be used as a carrier material for treating brain glioma and disabling
glioma neovasculatures.
PMID- 28402949
TI - Revisit 18F-fluorodeoxyglucose oncology positron emission tomography: "systems
molecular imaging" of glucose metabolism.
AB - 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography has become an
important tool for detection, staging and management of many types of cancer.
Oncology application of 18F-FDG bases on the knowledge that increase in glucose
demand and utilization is a fundamental features of cancer. Pasteur effect,
Warburg effect and reverse Warburg effect have been used to explain glucose
metabolism in cancer. 18F-FDG accumulation in cancer is reportedly
microenvironment-dependent, 18F-FDG avidly accumulates in poorly proliferating
and hypoxic cancer cells, but low in well perfused (and proliferating) cancer
cells. Cancer is a heterogeneous and complex "organ" containing multiple
components, therefore, cancer needs to be investigated from systems biology point
of view, we proposed the concept of "systems molecular imaging" for much better
understanding systems biology of cancer.This article revisits 18F-FDG uptake
mechanisms, its oncology applications and the role of 18F-FDG PET for "systems
molecular imaging".
PMID- 28402950
TI - Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in
murine macrophages.
AB - Degradation of lysosomal lipids requires lysosomal acid lipase (LAL), the only
intracellular lipase known to be active at acidic pH. We found LAL to be
expressed in murine immune cells with highest mRNA expression in macrophages and
neutrophils. Furthermore, we observed that loss of LAL in mice caused lipid
accumulation in white blood cells in the peripheral circulation, which increased
in response to an acute inflammatory stimulus. Lal-deficient (-/-) macrophages
accumulate neutral lipids, mainly cholesteryl esters, within lysosomes. The
cholesteryl ester fraction is particularly enriched in the PUFAs 18:2 and 20:4,
important precursor molecules for lipid mediator synthesis. To investigate
whether loss of LAL activity affects the generation of lipid mediators and to
eliminate potential systemic effects from other cells and tissues involved in the
pronounced phenotype of Lal-/- mice, we treated macrophages from Wt mice with the
LAL-specific inhibitor LAListat-2. Acute inhibition of LAL resulted in reduced
release of 18:2- and 20:4-derived mediators from macrophages, indicating that
lipid hydrolysis by LAL is an important source for lipid mediator synthesis in
macrophages. We conclude that lysosomes should be considered as organelles that
provide precursor molecules for lipid mediators such as eicosanoids.
PMID- 28402951
TI - Characterization of a secreted macrophage migration inhibitory factor homologue
of the parasitic nematode Haemonchus Contortus acting at the parasite-host cell
interface.
AB - Modulation and suppression of the immune response of the host by nematode
parasites have been reported extensively and the migration inhibitory factor
(MIF) is identified as one of the major immunomodulator. In the present study, we
cloned and produced recombinant MIF protein from the small ruminant's nematode
parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory
effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed
tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF
1 protein was predominantly localized at the body surface and internal surface of
the worm's gut. We demonstrated that rHCMIF-1 could be distinguished by antisera
from goats experimentally infected with H. contortus and could bind by goat
monocytes. The immunomodulatory effects of HCMIF-1 on cytokine secretion, MHC
molecule expression, NO production and phagocytosis were observed by co
incubation of rHCMIF-1 with goat monocytes. The results showed that the
interaction of rHCMIF-1 decreased the production of TNF-alpha, IL-1beta and IL
12p40, where as, it significantly increased the secretion of IL-10 and TGF beta
in goat monocytes. After rHCMIF-1 exposure, the expression of MHC-II on goat
monocytes was inhibited. Moreover, rHCMIF-1 could down-regulate the LPS induced
NO production of goat monocytes. Phagocytotic assay by FITC-dextran
internalization showed that rHCMIF-1 could inhibit the phagocytosis of goat
monocytes. Our findings provided potential targetas immunoregulator, and will be
helpful to elucidate the molecular basis of host-parasite interactions and search
for new potential protein as vaccine and drug target candidate.
PMID- 28402952
TI - Caveolin-1 scaffolding domain peptides enhance anti-inflammatory effect of heme
oxygenase-1 through interrupting its interact with caveolin-1.
AB - Caveolin-1(Cav-1) scaffolding domain (CSD) peptides compete with the plasma
membrane Cav-1, inhibit the interaction of the proteins and Cav-1, and re-store
the functions of Cav-1 binding proteins. Heme oxygenase-1 (HO-1) binds to Cav-1
and its enzymatic activity was inhibited. In this study, we investigated the
effect of CSD peptides on interaction between HO-1 and Cav-1, and on the HO-1
activity in vitro and in vivo. Our data showed that CSD peptides decreased the
compartmentalization of HO-1 and Cav-1, and increased the HO-1 activity both in
LPS-treated alveolar macrophages and in mice. Meanwhile, CSD peptides obviously
ameliorated the pathology changes in mice and lowered the following injury
indexes: the wet/dry ratio of lung tissues, total cell numbers in bronchoalveolar
lavage fluid and lactate dehydrogenase activity in the serum. Mechanistically, it
was firstly found that CSD peptides promoted alveolar macrophages polarization to
M2 phenotype and inhibited the IkappaB degeneration. Furthermore, CSD peptides
down-regulated the expression of IL-1beta, IL-6, TNF-alpha, MCP-1, and iNOS in
alveolar macrophages and in lung tissue. However, the protective role of CSD
peptides on LPS-induced acute lung injury in mice could be abolished by zinc
protoporphyrin IX (ZnPP, a HO-1 activity inhibitor). In summary, CSD peptides
have beneficial anti-inflammatory effects by restoring the HO-1 activity
suppressed by Cav-1 on plasma membrane.
PMID- 28402954
TI - Chaperone-mediated autophagy compensates for impaired macroautophagy in the
cirrhotic liver to promote hepatocellular carcinoma.
AB - Macroautophagy and chaperone-mediated autophagy (CMA) represent two major
lysosomal degradation processes and often compensate for one another to
facilitate cell survival. The aim of this study was to determine whether these
autophagy pathways could compensate for one another to promote HCC cell survival
in the cirrhotic liver. Analysis of normal liver tissue showed no expression of
glypican-3 or p62 proteins, suggesting that macroautophagy is the major
contributor to autophagic flux under non-pathological conditions. Of 46 cirrhotic
livers with HCC examined, 39 (84%) of HCCs showed increased expression of p62,
and 36 (78%) showed increased expression of glypican-3, while adjacent non
tumorous hepatocytes were negative for expression of p62 and glypican-3, similar
to normal liver tissue. These results suggest that macroautophagy flux is
impaired in HCC. Furthermore, more than 95% of HCCs showed altered expression of
LAMP-2A compared to the surrounding non-tumorous cirrhotic liver, consistent with
induction of CMA in HCC. Elevated expression of glucose-regulated protein 78
(GRP78) and heat shock cognate protein (Hsc70) were detected in 100% of HCC and
adjacent non-tumorous cirrhotic livers, suggesting that unresolved ER-stress is
associated with HCC risk in liver cirrhosis. Interestingly, inhibition of
lysosomal degradation using hydroxychloroquine (HCQ) induced expression of the
tumor suppressor p53, promoted apoptosis, and inhibited HCC growth, whereas
activation of autophagy using an mTOR inhibitor (Torin1) promoted HCC growth.
Results of this study suggest that induction of CMA compensates for the
impairment of macroautophagy to promote HCC survival in the cirrhotic liver.
PMID- 28402955
TI - Antiproliferative effect of somatostatin analogs in advanced gastro-entero
pancreatic neuroendocrine tumors: a systematic review and meta-analysis.
AB - A meta-analysis has systematically investigated the antineoplastic efficacy and
safety of somatostatin analogs (SSAs) in advanced gastro-entero-pancreatic
neuroendocrine tumors (GEP-NETs). Randomized controlled trials (RCTs) reporting
the hazard ratio (HR) for disease progression (DP) were evaluated. Response rate
and risk ratio (RR) for adverse events were also analyzed. A total of 289
patients (143 receiving SSAs vs. 146 placebo) were evaluated from two RCTs. A
significant benefit from SSAs in terms of disease control was observed (HR 0.41,
95% CI: 0.29 to 0.58, P < 0.01; I20%), response rate being 58.0% vs. 32.2%,
respectively.The occurrence of adverse events significantly differed from the
placebo arm only in terms of biliary stones (RR 3.79, 95% CI: 1.28 to 11.17, P =
0.02; I20%). In conclusion, SSAs showed an antiproliferative effect in advanced
GEP-NETs, with a good safety profile.
PMID- 28402953
TI - Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin
lymphoma: a summary of immunohistochemical studies.
AB - Immune checkpoint blockade therapeutics, notably antibodies targeting the
programmed death 1 (PD-1) receptor and its PD-L1 and PD-L2 ligands, are currently
revolutionizing the treatment of cancer. For a sizeable fraction of patients with
melanoma, lung, kidney and several other solid cancers, monoclonal antibodies
that neutralize the interactions of the PD-1/PD-L1 complex allow the
reconstitution of long-lasting antitumor immunity. In hematological malignancies
this novel therapeutic strategy is far less documented, although promising
clinical responses have been seen in refractory and relapsed Hodgkin lymphoma
patients. This review describes our current knowledge of PD-1 and PD-L1
expression, as reported by immunohistochemical staining in both non-Hodgkin
lymphoma cells and their surrounding immune cells. Here, we discuss the multiple
intrinsic and extrinsic mechanisms by which both T and B cell lymphomas up
regulate the PD-1/PD-L1 axis, and review current knowledge about the prognostic
significance of its immunohistochemical detection. This body of literature
establishes the cell surface expression of PD-1/PD-L1 as a critical determinant
for the identification of non-Hodgkin lymphoma patients eligible for immune
checkpoint blockade therapies.
PMID- 28402956
TI - Elevated dietary magnesium during pregnancy and postnatal life prevents ectopic
mineralization in Enpp1asj mice, a model for generalized arterial calcification
of infancy.
AB - Generalized arterial calcification of infancy (GACI) is an autosomal recessive
disorder caused by mutations in the ENPP1 gene. It is characterized by
mineralization of the arterial blood vessels, often diagnosed prenatally, and
associated with death in early childhood. There is no effective treatment for
this devastating disorder. We previously characterized the Enpp1asjmutant mouse
as a model of GACI, and we have now explored the effect of elevated dietary
magnesium (five-fold) in pregnant mothers and continuing for the first 14 weeks
of postnatal life. The mothers were kept on either control diet or experimental
diet supplemented with magnesium. Upon weaning at 4 weeks of age the pups were
placed either on control diet or high magnesium diet. The degree of
mineralization was assessed at 14 weeks of age by histopathology and a chemical
calcium assay in muzzle skin, kidney and aorta. Mice placed on high magnesium
diet showed little, if any, evidence of mineralization when their corresponding
mothers were also placed on diet enriched with magnesium during pregnancy and
nursing. The reduced ectopic mineralization in these mice was accompanied by
increased calcium and magnesium content in the urine, suggesting that magnesium
competes calcium-phosphate binding thereby preventing the mineral deposition.
These results have implications for dietary management of pregnancies in which
the fetus is suspected of having GACI. Moreover, augmenting a diet with high
magnesium may be beneficial for other ectopic mineralization diseases, including
nephrocalcinosis.
PMID- 28402957
TI - Chromatin state dynamics during NK cell activation.
AB - Studies of Natural Killer (NK) cell cytotoxicity have mainly focused on the
balance of activating and inhibitory receptors, signaling transduction, calcium
influx, formation of immune synapse, and cytolytic degranulation. However, little
is known about the chromatin state of NK cells and the impact of its changes
during target recognition. In this study, we investigate the contribution of
chromatin state dynamics during NK cell activation by comprehensively analyzing a
set of microarray data and two sets of Chromatin Immunoprecipitation-Sequencing
(ChIP-seq) data. We find that the expression of several histone demethylases and
methyltransferases was influenced upon stimulation. Furthermore, we notice that a
series of genes, including PI3KCA, NFATC1and TNFSF9, which play important roles
during NK cell activation, were at 'poised' state prior to activation, and that
modifications of H3K4me3 and H3K27me3 on these promotors were sensitive to
stimulation with Phorbol Myristate Acetate (PMA) and Ionomycin (Iono) in the
NK92MI cell line. Finally, we demonstrate that a series of small molecule
inhibitors, which are specific to H3K4 and H3K27 modification, enhance
degranulation or the expression levels of IFN-gamma and TNF-alpha. Our results
suggest that the histone modification state has a profound impact on NK cell
activation, and provide novel insights into the regulation of NK cellular
cytotoxicity and immunoregulatory function by chromatin state dynamics.
PMID- 28402958
TI - Thalidomide combined with transcatheter artierial chemoembolzation for primary
hepatocellular carcinoma: a systematic review and meta-analysis.
AB - OBJECTIVE: Transcatheter arterial chemoembolization (TACE) and thalidomide have
been used for treating primary hepatocellular carcinoma(HCC). This study aims to
evaluate the clinical efficacy and safety of thalidomide and TACE in primary HCC.
METHODS: Randomized controlled trials(RCTs) about efficacy and safety of
thalidomide combined with TACE for primary HCC were identified from the Cochrane
Library, Pubmed, Embase, CNKI, and Wan Fang until August, 2016. The retrieved
trials were reviewed and the data were extracted by two reviewers, independently.
Combined analyses of survival rates, overall response rate(ORR), disease control
rate(DCR), changes of KPS, parameters of cellular immunity and vascular
endothelial growth factor(VEGF), and adverse events were performed using RevMan
5.3 software. RESULTS: A total of 23 RCTs involving 1836 patients were included.
The results showed that thalidomide plus TACE was significantly superior in
increasing 6-month survival rate(OR=1.79, 95% CI:1.02-3.15, P=0.04), 1-year
survival rate(OR=1.76, 95% CI:1.38-2.24, P<0.0001), 1.5-year survival
rate(OR=4.72, 95% CI:2.64-8.43, P<0.001), 2-year survival rate(OR=1.78, 95%
CI:1.37-2.30, P<0.001), ORR(OR=1.89, 95% CI:1.48-2.42, P<0.0001), DCR(OR=2.62,
95% CI:1.90-3.63, P<0.001), improvement in cellular immunity(MD=0.63, 95% CI:0.45
0.80, P<0.0001), and reduction of VEGF(MD=-119.71, 95% CI:-135.75-103.68,
P<0.0001), when compared with TACE group. The incidences of gastrointestinal
reactions, myelosuppression, and liver dysfunction were similar between
combination group and TACE group(P>0.05). However, compared to TACE, the
combination of thalidomide and TACE had a higher incidence of drug rash(OR=6.35,
95% CI:2.75-14.68, P<0.0001). CONCLUSION: Our findings suggest that thalidomide
combined with TACE shows better clinical efficacy and tolerable adverse events in
patients with primary HCC when compared with TACE alone.
PMID- 28402959
TI - Meta-analysis of the association between variants in MAPT and neurodegenerative
diseases.
AB - Microtubule-associated protein tau (MAPT) gene is compelling among the
susceptibility genes of neurodegenerative diseases which include Alzheimer's
disease (AD), Parkinson's disease (PD), progressive supranuclear palsy (PSP),
corticobasal degeneration (CBD), frontotemporal dementia (FTD) and amyotrophic
lateral sclerosis (ALS). Our meta-analysis aimed to find the association between
MAPT and the risk of these diseases. Published literatures were retrieved from
MEDLINE and other databases, and 82 case-control studies were recruited. Six
haplotype tagging single-nucleotide polymorphisms (rs1467967, rs242557,
rs3785883, rs2471738, del-In9 and rs7521) and haplotypes (H2 and H1c) were
significantly associated with the above diseases. The odds ratios (ORs) and 95 %
confidence intervals (CIs) were evaluated by comparison in minor and major allele
frequency using the R software. This study demonstrated that different variants
in MAPT were associated with AD (rs2471738: OR= 1.04, 95%CI = 1.00 - 1.09; H2: OR
= 0.94, 95% CI = 0.91 - 0.97), PD (H2: OR = 0.76, 95% CI = 0.74 - 0.79), PSP
(rs242557: OR = 1. 96, 95% CI = 1. 71 - 2.25; rs2471738: OR = 1. 85, 95% CI = 1.
48 - 2.31; H2: OR = 0.20, 95% CI = 0.18 - 0.23), CBD (rs242557: OR = 2.51, 95%CI
= 1. 66 -3.78; rs2471738: OR = 2.07, 95%CI = 1. 32 -3.23; H2: OR = OR = 0.30, 95%
CI = 0.23 - 0.41) and ALS (H2: OR = 0.92, 95% CI = 0.86 - 0.98) instead of FTD
(H2: OR = 1.02, 95% CI = 0.78 - 1.32). In conclusion, MAPT is associated with
risk of neurodegenerative diseases, suggesting crucial roles of tau in
neurodegenerative processes.
PMID- 28402962
TI - Regeneration of cervical reserve cell-like cells from human induced pluripotent
stem cells (iPSCs): A new approach to finding targets for cervical cancer stem
cell treatment.
AB - Cervical reserve cells are epithelial progenitor cells that are pathologically
evident as the origin of cervical cancer. Thus, investigating the characteristics
of cervical reserve cells could yield insight into the features of cervical
cancer stem cells (CSCs). In this study, we established a method for the
regeneration of cervical reserve cell-like properties from human induced
pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like
cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell
markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2,
CD63, MMP7 and GDA. While iRCs expressed neither ERalpha nor ERbeta, they
expressed CA125. These data indicated that iRCs possessed characteristics of
cervical epithelial progenitor cells. iRCs secreted higher levels of several
inflammatory cytokines such as macrophage migration inhibitory factor (MIF),
soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10
(CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed
human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for
immune tolerance and carcinogenesis. Together with the fact that cervical CSCs
can originate from reserve cells, our data suggested that iRCs were potent immune
modulators that might favor cervical cancer cell survival. In conclusion, by
generating reserve cell-like properties from iPSCs, we provide a new approach
that may yield new insight into cervical cancer stem cells and help find new
oncogenic targets.
PMID- 28402963
TI - Identification of serum inflammatory markers as classifiers of lung cancer
mortality for stage I adenocarcinoma.
AB - BACKGROUND: Lung cancer is the leading cause of cancer-related mortality
worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung
cancer individuals in the USA. LDCT has resulted in increased detection of stage
I lung cancer for which the current standard of care is surgery alone. However,
approximately 30% of these patients develop recurrence and therefore are in need
of further treatment upon diagnosis. This study aims to explore blood-based
inflammatory biomarkers to identify patients at high-risk of mortality for which
additional treatment modalities can be offered at time of diagnosis. PATIENTS AND
METHODS: Recent work on a small panel of circulating cytokines identified
elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor
survival for lung cancer patients. To reflect the broader role of inflammation in
lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of
129 lung cancer patients selected from the National Cancer Institute-Maryland
case-control study. To reduce heterogeneity, we specifically focused our study on
stage I lung adenocarcinoma patients. RESULTS: We replicated the previous
observations that IL-6 is associated with prognosis of lung cancer and extended
its utility to prognosis in this highly-selected population of stage I lung
adenocarcinoma patients. In addition, we developed a multi-marker, combined
prognostic classifier that includes the pro-inflammatory Th-17 cell effector
cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly
adverse survival compared with patients with low levels (P for trend <0.0001).
Patients in the high risk group, with high levels of both proteins had a 5-year
survival rate of 46% in comparison to 93% for those with low levels of both
markers. Furthermore, we validated the same trends for the IL-6 and IL-17A
prognostic signature in an independent data set. CONCLUSIONS: The results
identified here justify further investigation of this novel, combined cytokine
prognostic classifier for the identification of high-risk stage I lung
adenocarcinoma patients. This classifier has the much-needed potential to
identify patients at high risk of recurrence and thus prospectively identify the
subset of patients requiring more aggressive treatment regimens at the time of
diagnosis.
PMID- 28402964
TI - SET mediates TCE-induced liver cell apoptosis through dephosphorylation and
upregulation of nucleolin.
AB - Trichloroethylene (TCE) is an occupational and environmental chemical that can
cause severe hepatotoxicity. While our previous studies showed that the
phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis,
the molecular mechanisms remain elusive. Using quantitative phosphoproteomic
analysis, we report here that nucleolin is a SET-regulated phosphoprotein in
human liver HL-7702 cells. Functional analysis suggested that SET promoted
dephosphorylation of nucleolin, decreased its binding to its transcriptional
activator, c-myc, and upregulated nucleolin expression in TCE-treated cells.
Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when
nucleolin was downregulated with specific siRNAs. These findings indicate that
TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and
overexpression of nucleolin.
PMID- 28402965
TI - Curcumin enhances the effects of irinotecan on colorectal cancer cells through
the generation of reactive oxygen species and activation of the endoplasmic
reticulum stress pathway.
AB - Although initially effective against metastatic colorectal cancer (CRC),
irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin
is well known for its anti-cancer effects in many cancers, including CRC. Here,
we describe reactive oxygen species (ROS) generation and endoplasmic reticulum
(ER) stress as important mechanisms by which curcumin enhances irinotecan's
effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan
for 24 h, and then evaluated using cell proliferation assays, cell apoptosis
assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements
and immunoblotting for key ER stress-related proteins. We found that cell
viability was inhibited and apoptosis was increased, accompanied by ROS
generation and ER stress activation in CRC cells treated with curcumin alone or
in combination with irinotecan. Blocking ROS production attenuated the expression
of two markers of ER stress: binding of immunoglobulin protein (BIP) and
CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP
expression using RNA interference also inhibited ROS generation. These results
demonstrated that curcumin could enhance the effects of irinotecan on CRC cells
by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and
that these effects may be mediated, in part, by ROS generation and activation of
the ER stress pathway.
PMID- 28402967
TI - Surface curvature in triply-periodic minimal surface architectures as a distinct
design parameter in preparing advanced tissue engineering scaffolds.
AB - Reproduction of the anatomical structures and functions of tissues using cells
and designed 3D scaffolds is an ongoing challenge. For this, scaffolds with
appropriate biomorphic surfaces promoting cell attachment, proliferation and
differentiation are needed. In this study, eight triply-periodic minimal surface
(TPMS)-based scaffolds were designed using specific trigonometric equations,
providing the same porosity and the same number of unit cells, while presenting
different surface curvatures. The scaffolds were fabricated by stereolithography
using a photocurable resin based on the biocompatible, biodegradable and rubber
like material, poly(trimethylene carbonate) (PTMC). A numerical approach was
developed to calculate the surface curvature distributions of the TPMS
architectures. Moreover, the scaffolds were characterized by scanning electron
microscopy, micro-computed tomography and water permeability measurements. These
original scaffold architectures will be helpful to decipher the biofunctional
role of the surface curvature of scaffolds intended for tissue engineering
applications.
PMID- 28402966
TI - An injectable nucleus pulposus cell-modified decellularized scaffold:
biocompatible material for prevention of disc degeneration.
AB - We developed a nucleus pulposus cell (NPC)-modulated decellularized small
intestinal submucosa (SIS) scaffold, and assessed the ability of this material to
prevent Intervertebral disc degeneration (IVD) degeneration. Decellularized
porcine SIS was squashed into particles and the biological safety and efficiency
of these particles were evaluated. Next, SIS particles were seeded with rabbit
NPCs, cultured for two months in vitro, decellularized again and suspended for
intervertebral injection. We demonstrated that use of the decellularization
protocol resulted in the removal of cellular components with maximal retention of
extracellular matrix. The xenogeneic decellularized SIS did not display
cytotoxicity in vitro and its application prevented NPC degradation. Furthermore,
the xenogeneic SIS microparticles were effective in preventing IVD progression in
vivo in a rabbit disc degeneration model. In conclusion, our study describes an
optimized method for decellularized SIS preparation and demonstrated that the
material is safe and effective for treating IVD degeneration.
PMID- 28402968
TI - A cell-printing approach for obtaining hASC-laden scaffolds by using a
collagen/polyphenol bioink.
AB - In the cell-printing process, bioink has been considered as an extremely
important component for successful fabrication of macroscale cell-laden
structures. Bioink should be non-toxic, biocompatible, and printable. To date,
alginate has been widely used as a whole or partial component of bioink because
it is non-toxic to embedded cells and even it can provide good printability with
rapid gelation under calcium ions. However, alginate bioinks do not possess cell
activating ability. To overcome the shortcomings of alginate-based bioinks, a new
collagen bioink, which was mixed with human adipose stem cells (hASCs) and
crosslinked with a polyphenol (tannic acid), was proposed. The feasibility of the
bioink was demonstrated using several in vitro assessments for comparison of the
macroscale porous cell-laden collagen/polyphenol structure containing the hASCs
with the conventional alginate-based cell-laden structure. The levels of the
metabolic activity, including the cell viability and cell proliferation, of the
cell-laden collagen structure were significantly higher than those of the control
(alginate-based cell-laden structure). The results show that the newly designed
bioink and cell-laden structure are potentially new outstanding components for
regeneration of various tissues.
PMID- 28402969
TI - Cytogenetic Characterization of Brown Howler Monkeys, Alouatta guariba clamitans
(Atelidae, Platyrrhini): Meiotic Confirmation of an X1X1X2X2X3X3/X1X2X3Y1Y2 Sex
Chromosome System.
AB - For brown howler monkeys (Alouatta guariba clamitans), diploid chromosome numbers
varying from 2n = 45 to 2n = 52, with XX/XY, X1X1X2X2/X1X2Y, and
X1X1X2X2X3X3/X1X2X3Y1Y2 sex chromosome systems have been described by mitotic
studies but still await confirmation by meiotic analyses. We analyzed 3 male
individuals sampled in the wild (in the municipality of Santa Maria, RS, Brazil)
as well as 1 male and 1 female individual in captivity at the Sao Braz breeding
center. Peripheral blood samples and testicular biopsies were taken. We found
different diploid numbers for both sexes in somatic cells, 2n = 45,X1X2X3Y1Y2 in
males and 2n = 46,X1X1X2X2X3X3 in females, with 4 metacentric (9-12), 7
submetacentric (1-6, 8), and 9 acrocentric autosomal chromosome pairs (13-20,
22). X1 and X2 were submetacentric chromosomes, while X3, Y1, and Y2 were
acrocentric ones. Spermatocyte microspreads were examined for synaptonemal
complexes. Pachytene spermatocyte analysis was done to verify the chromosome
number and morphologies observed in mitotic karyotypes. Immunodetection was
performed using anti-SMC3 and anti-CREST antibodies. The presence of a sex
chromosome pentavalent X1X2X3Y1Y2 in the males was confirmed by C-banding in
metaphase I and by immunodetection in prophase I by the clear identification of 5
centromeres. The G-banded karyotype corresponded to that previously described for
A. g. clamitans in the south of Brazil (Curitiba, Parana State, and Blumenau,
Santa Catarina State) and for the Misiones Province, Argentina.
PMID- 28402970
TI - The Genotyping Resistance Profile of the Pol Gene Detected in Blood of Newly
Diagnosed HIV-Positive Men Is Durably Archived in the Gut Whatever the Time of
Initiation of cART.
AB - OBJECTIVE: To evaluate the mutational patterns on the pol gene of the main HIV-1
strain archived in cell genome of 10 chronically infected men according to their
clinical and therapeutic history. The genotyping resistance profiles were
compared between the first blood plasma available at the time of HIV diagnosis
and rectal biopsies and PBMC sampled 1-5 years after the initiation of combined
antiretroviral therapy (cART). METHODS: HIV-1 RNA and cell-associated HIV-1 DNA
were quantified by Abbott Real-Time HIV-1 and Generic HIV(r) DNA cell
(Biocentric) assays. The mutations in protease and reverse transcriptase genes
were assessed by the Trugene(r) assay (Siemens). The C2V3 region was amplified to
determine the viral tropism. RESULTS: In 9 patients, slight or no differences
were observed between the 3 resistance profiles. Those mostly detected were
related to the resistance to nucleos(t)ide (D67N, L210W, T215A, T69D) and
nonnucleoside (K103N, V106I, V179I) inhibitors. In 1 rilpivirine-treated patient,
the M230I mutation was detected in PBMC. No change of viral tropism was observed
between samples. CONCLUSION: These data suggest that resistance mutations
harbored by the main HIV strain in plasma at the time of diagnosis are durably
archived in DNA cells whatever the delay between infection and initiation of
therapy in patients well controlled by cART.
PMID- 28402971
TI - Implicating Receptor Activator of NF-kappaB (RANK)/RANK Ligand Signalling in
Microglial Responses to Toll-Like Receptor Stimuli.
AB - Inflammation in the perinatal brain caused by maternal or intrauterine fetal
infection is now well established as an important contributor to the development
of perinatal brain injury. Exposure to inflammatory products can impair perinatal
brain development and act as a risk factor for neurological dysfunction,
cognitive disorders, cerebral palsy, or preterm birth. Pre-exposure to
inflammation significantly exacerbates brain injury caused by hypoxic/ischaemic
insult. Tumour necrosis factor (TNF) is a family of cytokines largely involved in
inflammation signalling. In our previous study, we identified the importance of
TNF-related apoptosis-inducing ligand (TRAIL) signalling in the development of
perinatal brain injury. We observed a significant increase in the expression
levels of a soluble decoy receptor for TRAIL, osteoprotegerin (OPG). Besides
TRAIL, OPG is able to bind the receptor activator of the NF-kappaB (RANK) ligand
(RANKL) and inhibit its signalling. The function of the RANK/RANKL/OPG system in
the brain has not come under much scrutiny. The aim of this research study was to
elucidate the role of RANK, RANKL, and OPG in microglial responses to the
proinflammatory stimuli lipopolysaccharide (LPS) and polyinosinic-polycytidylic
acid (Poly I:C). Here, we show that RANK signalling is important for regulating
the activation of the BV2 microglial cell line. We found that LPS treatment
causes a significant decrease in the expression of RANK in the BV2 cell line
while significantly increasing the expression of OPG, Toll-like receptor (TLR)3,
and the adaptor proteins MyD88 and TRIF. We found that pretreatment of BV2 cells
with RANKL for 24 h before the LPS or Poly I:C exposure decreases the expression
of inflammatory markers such as inducible nitric oxide synthase and
cyclooxygenase. This is accompanied by a decreased expression of the TLR adaptor
proteins MyD88 and TRIF, which we observed after RANKL treatment. Similar results
were obtained in our experiments with primary mouse microglia. Using recently
developed CRISPR/Cas9 technology, we generated a BV2 cell line lacking RANK (RANK
/- BV2). We showed that most effects of RANKL pretreatment were abolished,
thereby proving the specificity of this effect. Taken together, these findings
suggest that RANK signalling is important for modulating the inflammatory
activation of microglial cells to a moderate level, and that RANK attenuates
TLR3/TLR4 signalling.
PMID- 28402972
TI - EEG - A Valuable Biomarker of Brain Injury in Preterm Infants.
AB - This review focuses on the role of electroencephalography (EEG) in monitoring
abnormalities of preterm brain function. EEG features of the most common
developmental brain injuries in preterm infants, including intraventricular
haemorrhage, periventricular leukomalacia, and perinatal asphyxia, are described.
We outline the most common EEG biomarkers associated with these injuries, namely
seizures, positive rolandic sharp waves, EEG suppression/increased interburst
intervals, mechanical delta brush activity, and other deformed EEG waveforms,
asymmetries, and asynchronies. The increasing survival rate of preterm infants,
in particular those that are very and extremely preterm, has led to a growing
demand for a specific and shared characterization of the patterns related to
adverse outcome in this unique population. This review includes abundant high
quality images of the EEG patterns seen in premature infants and will provide a
valuable resource for everyone working in developmental neuroscience.
PMID- 28402973
TI - Low Risk of Developing Chronic Hepatitis E in Heart Transplant Recipients: A
Prospective 2-Year Follow-Up Study.
PMID- 28402974
TI - Cardiac Changes and Their Association with Fetuin-A and Fibroblast Growth Factor
23 in Children with Chronic Kidney Disease.
AB - AIMS: In children with chronic kidney disease (CKD), fetuin-A and fibroblast
growth factor-23 (FGF-23) have been implicated in the mechanism and progression
of several cardiac changes. This study aimed to determine the types and rates of
cardiac changes in children with CKD and their association with fetuin-A, FGF-23,
and other cardiovascular risk factors (CVRFs). METHODS: This comparative cross
sectional study recruited 88 children (5-18 years): 27 CKD I with a glomerular
filtration rate (GFR) >90 mL/min/1.73 m2 and 61 with a GFR of <90 mL/min/1.73 m2
(29 CKD II-IV, 32 CKD V-dialysis). Each patient had a short demographic and
clinical history taken along with a physical examination. Blood was taken and
sent for routine tests and for fetuin-A and FGF-23 assay. All patients had an
echocardiogram to evaluate cardiac structure and function. RESULTS: The
distribution of left atrial diameter (LAD) and left ventricular (LV) mass
differed significantly (p < 0.05) across the different CKD groups. Abnormal LAD
was seen in 10% of patients; LV hypertrophy (LVH) in 27%; LV systolic dysfunction
in 6% and diastolic dysfunction in 1 patient. Fetuin-A was the only independent
predictor for abnormal LAD; mean arterial pressure was independently associated
with concentric LVH, and age and hypoalbuminemia with eccentric LVH. Overall, the
dialysis group had the highest rate of cardiac changes and associated risk
factors. CONCLUSION: Though not common, the importance of left atrial changes in
children with CKD is highlighted along with the need to address modifiable CVRFs
such as hypertension and hypoalbuminemia.
PMID- 28402975
TI - Frequent pUL27 Variations in HIV-Infected Patients.
AB - OBJECTIVE: Drug-resistant isolates of human cytomegalovirus (HCMV) have led to
the development of new anti-HCMV drugs. Maribavir (MBV) is a novel inhibitor of
the HCMV viral kinase. Resistance to MBV is mapped to gene UL27, a viral nuclear
protein. In this study, we investigated UL27 polymorphisms in MBV-naive HIV
positive and HCMV congenitally infected clinical samples. METHODS: DNA was
extracted from 20 CMV-positive HIV (9/20) and congenitally infected (11/20)
patients and used for UL27 polymerase chain reaction amplification. Sanger
sequencing and multiple sequence alignment of products was performed. RESULTS:
K90 was the most prevalent polymorphism in both HIV-positive and congenitally
infected patients. Polymorphisms Q54, D123, and R107 (10%) were seen in more than
one sample. There were significantly more polymorphisms in the HIV-positive
samples (p = 0.038). CONCLUSION: HCMV pUL27 is highly variable in adult
immunocompromised HIV-positive patients.
PMID- 28402976
TI - Apelin-13 Protects against Ischemic Blood-Brain Barrier Damage through the
Effects of Aquaporin-4.
AB - BACKGROUND: Apelin-13 has been found to have protective effects on many
neurological diseases, including cerebral ischemia. However, whether Apelin-13
acts on blood-brain barrier (BBB) disruption following cerebral ischemia is
largely unknown. Aquaporin-4 (AQP4) has a close link with BBB due to the high
concentration in astrocyte foot processes and regulation of astrocytes function.
Here, we aimed to test Apelin-13's effects on ischemic BBB injury and examine
whether the effects were dependent on AQP4. METHODS: We detected the expression
of AQP4 induced by Apelin-13 injection at 1, 3, and 7 days after middle cerebral
artery occlusion. Meanwhile, we examined the effects of Apelin-13 on neurological
function, infarct volume, and BBB disruption owing to cerebral ischemia in wild
type mice, and tested whether such effects were AQP4 dependent by using AQP4
knock-out mice. Furthermore, we assessed the possible signal transduction
pathways activated by Apelin-13 to regulate AQP4 expression via astrocyte
cultures. RESULTS: It was found that Apelin-13 highly increased AQP4 expression
as well as reduced neurological scores and infarct volume. Importantly, Apelin-13
played a role of BBB protection in both types of mice by reducing BBB
permeability, increased vascular endothelial growth factor, upregulated
endothelial nitric oxide synthase, and downregulated inducible NOS. In
morphology, we demonstrated Apelin-13 suppressed tight junction opening and
endothelial cell swelling via electron microscopy detection. Meanwhile, Apelin-13
also alleviated apoptosis of astrocytes and promoted angiogenesis. Interestingly,
effects of AQP4 on neurological function and infarct volume varied with time
course, while AQP4 elicited protective effects on BBB at all time points.
Statistical analysis of 2-way analysis of variance with replication indicated
that AQP4 was required for these effects. In addition, Apelin-13 upregulated
phosphorylation of extracellular signal-regulated kinase (ERK) and Akt as well as
AQP4 protein in cultured astrocytes. The latter was inhibited by ERK and
phosphatidylinositol 3'-kinase (PI3K) inhibitors. CONCLUSION: Our data suggest
that Apelin-13 protects BBB from disruption after cerebral ischemia both
morphologically and functionally, which is highly associated with the increased
levels of AQP4, possibly through the activation of ERK and PI3K/Akt pathways.
This study provides double targets to protection of ischemic BBB damage, which
can present new insights to drugs development.
PMID- 28402977
TI - Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis.
AB - In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic
vascular resistance and portal blood flow. Significant vasodilation in the
arterial splanchnic district is crucial for an increase in portal flow. In this
pathological condition, increased levels of circulating endogenous vasodilators,
including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids,
glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular
response to vasoconstrictors are the main mechanisms underlying splanchnic
vasodilation. In this review, the molecular pathways leading to splanchnic
vasodilation will be discussed in detail.
PMID- 28402978
TI - Telecommunications Network Measurements of Online Gambling Behavior in
Switzerland: A Feasibility Study.
AB - BACKGROUND: Methodological shortcomings of gambling studies relying on self
report or on data sets derived from gambling operators tend to result in biased
conclusions. The aim of this study was to analyze online gambling behavior using
a novel network database approach. METHODS: From October 13 to October 26, 2014,
telecommunications network data from a major telecommunications provider in
Switzerland were analyzed. Netflows between mobile devices and a poker operator
were quantified to measure the gambling duration and session number. RESULTS:
Time spent gambling during night and working hours was compared between devices
with longest (red group), intermediate (orange group), and shortest gambling time
(green group). Online gambling behavior differed depending on overall gambling
time, F (2, 3,143). Night and working hours gambling was the highest in the red
group (53%), compared to the orange (50.1%) and the green groups (41.5%). Post
hoc analyses indicated significant differences between the orange and green
groups (p < 0.05). No differences were observed between the red and orange groups
(p = 0.850), and the red and green groups (p = 0.053). CONCLUSIONS: On mobile
devices, distinct gambling patterns were observed depending on the overall
gambling time. This methodology could also be used to investigate online gaming,
social media use, and online pornography.
PMID- 28402979
TI - The Inhibitory Effect of Eplerenone on Cell Proliferation in the Contralateral
Kidneys of Rats with Unilateral Ureteral Obstruction.
AB - BACKGROUND: The unilateral ureteral obstruction (UUO) model not only induces
renal interstitial fibrosis in the obstructed kidney but also induces injury in
the contralateral kidney. We hypothesized that activation of the
mineralocorticoid receptor (MR) may induce fibrosis in the early stage of UUO.
METHODS: Thirty male Sprague-Dawley rats weighting 200 +/- 10 g were used in this
study and randomly divided into 3 groups: a UUO group, a UUO and eplerenone
group, and a sham group. The contralateral kidney and plasma were harvested for
further study 10 days after surgery. RESULTS: The level of plasma aldosterone
(869.95 +/- 55.851 pg/mL) was significantly higher in the UUO group than that in
the sham group (478.581 +/- 36.186 pg/mL vs. UUO, p < 0.05). The infiltrated
inflammatory cells (F4/80) and deposited collagens were increased significantly
in the contralateral kidneys in the UUO group compared to those in the sham
group, which were decreased by eplerenone. However, proliferating cell nuclear
antigen was increased 2.47 times in the UUO group compared to the sham group in
the contralateral kidney (p < 0.01), and those changes are attenuated by
eplerenone. The expression of SGK-1 protein and mRNA was upregulated in the
contralateral kidney in the UUO group, which is suppressed by eplerenone
treatment. NF-kappaB pathway effecters were also changed markedly in the
contralateral kidney in the UUO group and partly reversed by eplerenone.
CONCLUSION: Aldosterone induces inflammatory cell proliferation via the MR/SGK-1
and NF-kappaB pathways and eventually leads to fibrosis in the contralateral
kidney.
PMID- 28402980
TI - ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasia:
Peptide Receptor Radionuclide Therapy with Radiolabeled Somatostatin Analogues.
PMID- 28402981
TI - Prenatal Nonvisualization of the Gallbladder: A Diagnostic and Prognostic
Dilemma.
AB - INTRODUCTION: Nonvisualization of the fetal gallbladder has been associated with
benign conditions such as isolated gallbladder agenesis or severe diseases such
as biliary atresia (BA). Recently, gamma-glutamyl transpeptidase (GGTP) fetal
blood levels were reported as useful after 22 weeks. OBJECTIVE: To determine the
contribution of fetal blood GGTP levels after 22 weeks, based on 2 cases. Case 1:
20+4-week secundipara, with subcutaneous edema and pleural effusion. At 24+4
weeks, the gallbladder could not be visualized. Progressive hydrops deterioration
was observed. 32+2-week magnetic resonance imaging (MRI) confirmed
nonvisualization of the gallbladder. BA was suspected. The patient decided to
terminate the pregnancy and fetal blood sample was obtained at feticide. GGTP was
573 IU/L. Fetal necropsy confirmed BA. Case 2: At the 22+6- and 24+0-week
ultrasound scan, the gallbladder could not be visualized. Amniocentesis was
offered, but declined by the patient. MRI at 35+0 weeks failed also to visualize
it. Fetal cord blood sample at delivery was obtained, and GGTP was 129 IU/L.
Ultrasound confirmed gallbladder agenesis with normal extra- and intrahepatic
bile ducts. CONCLUSION: Cases of nonvisualized gallbladder after 22 weeks have
rarely been reported in the literature. Until now, no standard management has
been proposed. Our cases support the potential usefulness of fetal blood
digestive enzymes.
PMID- 28402982
TI - Delayed Dispersal and Immigration in Equatorial Sakis (Pithecia aequatorialis):
Factors in the Transition from Pair- to Group-Living.
AB - Saki monkeys (Pithecia spp.) live in pairs and small groups, sometimes with more
than 1 same-sex adult. Previous studies have not been able to distinguish
additional, unrelated adults from adult-sized offspring, but both can influence
social relationships and mating strategies, albeit in different ways. In this
study, we documented the immigration of an adult male equatorial saki (P.
aequatorialis) into a group following the departure of the previous resident
male. At immigration, the group contained an adult female, her 5-year-old (adult
age) and 1.5-year-old daughters, and her 1-month-old infant. We used nearest
neighbor, approach, grooming, playing, aggression, and copulation data to
describe the social dynamics between the immigrant male and the 2 adult females.
In the 12 months following his arrival, the immigrant male tended to be closer to
and groom the adult daughter more than the mother, but he mated with both
females. Both females interacted more with the immigrant male than with each
other, and both females eventually reproduced. These observations provide
evidence that in equatorial sakis, adult offspring may delay dispersal and
reproduce within their natal group, thus transitioning from groups of
reproductive pairs to groups with more than 1 reproductive adult of the same sex.
PMID- 28402983
TI - Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept
for Typical Neovascular Age-Related Macular Degeneration.
AB - PURPOSE: The aim of this study was to clarify the 1-year outcomes of pro re nata
(PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical
neovascular age-related macular degeneration (tAMD) after the initial 3 monthly
IVA. METHODS: We conducted a prospective, interventional study. Fifty-eight
treatment-naive patients with tAMD were randomly assigned to the PRN (30
patients) or the bimonthly (28 patients) treatment group. Both groups initially
received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT),
and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis
was performed to identify factors associated with the best-corrected visual
acuity (BCVA). RESULTS: BCVA was significantly improved only in the bimonthly
group at 12 months. CRT and CCT were significantly decreased in both groups.
Subanalysis showed that the only factor associated with BCVA improvement at 12
months was the existence of pigment epithelial detachment at baseline.
CONCLUSIONS: BCVA showed significant improvement only in the bimonthly group but
not in the PRN group at 12 months.
PMID- 28402984
TI - Contribution of Hormonal Cytology in Girls and Adolescents to Reproductive
Health: A Traditional Technique Monitoring Recent Problems.
AB - OBJECTIVE: To study the contribution of hormonal cytology in contemporary
disturbances of fertility. DESIGN: Over a 10-year period (2006-2015), 6,688
vaginal fornix cytologies of 2,350 patients were investigated. For a more
detailed analysis, a 3-year period from 2013 to 2015 was chosen. Four hundred and
fifty-two patients were investigated, many of them several times and for a period
longer than the 3 years analyzed. RESULTS: The main disorders examined and
treated via a gentle hormonal medication support and life style corrections by a
pediatric gynecologist were: pubertas praecox - thelarche praecox and early
menarche; dysfunctional juvenile metrorrhagia; central and peripheral endocrine
disorders; eating disorders - anorexia mentalis and bulimia; obesity; excessive
sport activities; autoimmune disorders, and others. Normalization of the
menstrual cycle was achieved while monitoring progress with a series of hormonal
cytologies in a majority of patients. CONCLUSIONS: Hormonal cytology is a non
invasive and economical method, illustrating the direct effect of steroid on
target cells. It contributes to reproductive health support by: (a) indicating
the possible need and type of steroid therapy; (b) monitoring the normalization
of cycle disturbances; (c) ruling out or indicating the need for more detailed
steroid metabolism investigation. Thus, it represents a basic but valuable means
of examination in child and adolescent gynecology.
PMID- 28402985
TI - The past, present, and future of ventilation during cardiopulmonary
resuscitation.
AB - PURPOSE OF REVIEW: To evaluate the past and present literature on ventilation
during out of hospital cardiac arrest, highlighting research that has informed
current guidelines. RECENT FINDINGS: Previous studies have studied what are
optimal compression-to-ventilation ratios, ventilation rates, and methods of
ventilation. Continuous chest compression cardiopulmonary resuscitation (CPR) has
not shown to provide a significant survival benefit over the traditional 30 : 2
CPR. The optimal ventilation rate is recommended at 8 to 10 breaths per minute.
Methods such as capnography and thoracic impedance are being used to evaluate
ventilation in research studies. SUMMARY: Future out of hospital cardiac arrest
studies are still exploring how to optimize the delivery of ventilation during
the initial stages of resuscitation. More prospective studies focusing on
ventilation are needed to inform guidelines.
PMID- 28402986
TI - No small matter: pediatric resuscitation.
AB - PURPOSE OF REVIEW: To present advancements in pediatric cardiac arrest research,
highlighting articles most relevant to clinical practice published since the
latest international guidelines for cardiopulmonary resuscitation (CPR). RECENT
FINDINGS: Clinical trials examining targeted temperature management in children
support avoidance of hyperthermia for both pediatric in-hospital cardiac arrest
(PIHCA) and out-of-hospital cardiac arrest (POHCA), but no statistically
significant outcome differences were confirmed comparing 33 and 36 degrees C in
the limited populations studied. Retrospective analyses of population-based POHCA
registries revealed several associations: both bystander CPR and public-access
defibrillation were associated with improved POHCA outcomes; conflicting results
overshadow the benefits of conventional versus compression-only CPR;
extracorporeal CPR was associated with improved PIHCA outcomes regardless of
cause; intubation in PIHCA was associated with decreased survival, whereas there
were no significant differences in outcomes between advanced airway management
and bag-valve-mask ventilation in POHCA; and early epinephrine delivery in
nonshockable rhythms during PIHCA was associated with improved outcomes. Length,
age, and weight-based dosing systems can reduce time to medication delivery,
quantitative errors, and anxiety among care providers. SUMMARY: Mounting evidence
continues to align management priorities for resuscitation of children and
adults.
PMID- 28402988
TI - Incidence and Factors Predictive of Dysphagia and Dysphonia After Anterior
Operation With Multilevel Cervical Spondylotic Myelopathy.
AB - STUDY DESIGN: Retrospective database analysis. OBJECTIVE OF THE STUDY: The
objective of the study was to quantify the incidence of dysphagia and dysphonia
and assess the associated risk factors after multilevel cervical anterior
operation. SUMMARY OF BACKGROUND DATA: Anterior approach for multilevel cervical
spondylotic myelopathy has been developed and obtained favorable outcomes. As
number of fused levels increased, the operation difficulty, invasiveness and
operative risks are higher. Meanwhile, the 2 most common postoperative
complications described in the literature are dysphonia and dysphagia. MATERIALS
AND METHODS: Two hundred thirty-six multilevel cervical spondylotic myelopathy
patients between October 2004 and June 2012 were included in the study. All
patients undergoing anterior operation, and incidences of dysphagia were
identified. Risk factors were assessed using logistic regression. RESULTS: At a
minimum of 1 year after operation, 70.6% (n=156) were 3-level anterior operation
and 29.4% (n=65) were 4-level anterior operation. The overall dysphagia rate was
23.1% (51 patients). The overall dysphonia rate was 28.5% (63 patients). Logistic
regression analysis demonstrated that risk factors for dysphagia included age,
operation time and lack of tracheal traction exercise. Age, operation time were 2
factors significantly related to dysphonia. CONCLUSIONS: The incidence of
postoperative dysphagia and dysphonia is relative higher after multilevel
anterior operation. Age and operation time carry a greater risk of postoperative
dysphagia and dysphonia. Tracheal traction exercise might help patients reduce
postoperative dysphagia. Sufficient preoperative preparation and evaluation
combining with proficient and precise operation technique are suggested when
multilevel anterior fusion is performed.
PMID- 28402991
TI - Widening the spectrum of inflammatory disorders of the central nervous system.
PMID- 28402989
TI - Serial assessment of bioresorbable-polymer sirolimus-eluting stent by coronary
angioscopy and optical coherence tomography.
PMID- 28402992
TI - Editorial: introducing the new Co-Editors-in-Chief of Current Opinion in
Neurology.
PMID- 28402987
TI - New insights into redox homeostasis as a therapeutic target in B-cell
malignancies.
AB - PURPOSE OF REVIEW: The goal of this review is to summarize recent advances in our
understanding of the regulation of redox homeostasis and the subtype-specific
role of antioxidant enzymes in B-cell-derived malignancies. Furthermore, it
presents selected prooxidative therapeutic strategies against B-cell neoplasms.
RECENT FINDINGS: Recent reports have shown that the disturbed redox homeostasis
in B-cell malignancies is regulated by cancer-specific signaling pathways and
therefore varies between the individual subtypes. For instance, in a subtype of
diffuse large B-cell lymphoma with increased oxidative phosphorylation, elevated
reactive oxygen species are accompanied by higher levels of thioredoxin and
glutathione and inhibition of either of these systems is selectively toxic to
this subtype. In addition, growing number of small molecule inhibitors targeting
antioxidant enzymes, such as auranofin, SK053, adenanthin, or decreasing
glutathione level, such as imexon, buthionine sulfoximine, and L-cysteinase,
trigger specific cytotoxic effects against B-cell malignancies. Lastly, attention
is drawn to recent reports of effective treatment modalities involving
prooxidative agents and interfering with redox homeostasis provided by stromal
cells. SUMMARY: Recent findings reveal important differences in redox homeostasis
within the distinct subsets of B-cell-derived malignancies that can be
therapeutically exploited to improve existing treatment and to overcome drug
resistance.
PMID- 28402993
TI - Volumetric laser endomicroscopy in the management of Barrett's esophagus.
AB - PURPOSE OF REVIEW: The incidence of esophageal adenocarcinoma is on the rise
despite widespread appreciation that the precursor lesion is Barrett's esophagus.
Studies have shown that some patients known to have Barrett's esophagus develop
cancer despite their enrollment in conventional endoscopic surveillance programs.
This highlights the need for advanced endoscopic imaging to help identify early
neoplasia and prevent its progression to esophageal cancer. Recently, a wide
field, second-generation optical coherence tomography endoscopic platform called
volumetric laser endomicroscopy (VLE) was cleared by the Food and Drug
Administration and made commercially available for advanced imaging in Barrett's
esophagus. RECENT FINDINGS: The current review discusses current literature on
VLE imaging in Barrett's esophagus. Based on ex-vivo studies, criteria have been
established for identifying Barrett's esophagus-associated neoplasia. In
addition, recent studies, case series, and case reports have demonstrated that
VLE is well tolerated, efficacious, and can target neoplasia. SUMMARY: VLE is a
new advanced imaging platform for Barrett's esophagus with considerable promise
to target Barrett's esophagus-associated neoplasia. The following are needed to
establish VLE's clinical role: studies showing incremental yield of dysplasia
detection using VLE, studies to determine VLE's in-vivo diagnostic accuracy for
identifying and classifying Barrett's esophagus-associated neoplasia, and studies
on the cost-efficacy of VLE.
PMID- 28402995
TI - Etiopathogenesis of inflammatory bowel disease: today and tomorrow.
AB - PURPOSE OF REVIEW: Crohn's disease and ulcerative colitis, the two major forms of
inflammatory bowel disease (IBD), represent chronic diseases of unknown cause,
and they are regarded as prototypical complex diseases. Despite all the recent
advances, a complete appreciation of the pathogenesis of IBD is still limited. In
this review, we present recent information contributing to a better understanding
of mechanisms underlying IBD. RECENT FINDINGS: Here, we attempt to highlight
novel environmental triggers, data on the gut microbiota, its interaction with
the host, and the potential influence of diet and food components. We discuss
recent findings on defective signaling pathways and the potential effects on the
immune response, and we present new data on epigenetic changes, inflammasome, and
damage-associated molecular patterns associated with IBD. SUMMARY: The continuing
identification of several epigenetic, transcriptomic, proteomic, and metabolomic
alterations in patients with IBD reflects the complex nature of the disease and
suggests the need for innovative approaches such as systems biology for
identifying novel relevant targets in IBD.
PMID- 28402996
TI - Lars Vistnes, MD, 1927-2016.
PMID- 28402998
TI - The Gaza Hand Board.
AB - This article describes an economical, versatile hand board that was conceived in
Gaza during a surgical mission in the absence of commercially available hand
holding devices. It was initially created to allow access and immobilization of
the hand when addressing volar digital burn contractures. It has been applied
subsequently during 5 further missions and now forms a standard part of our
surgical kit. We present it to provide others with an easy solution should they
need to release complex hand contractures and not have any assistant or
instrument to immobilize the hand.
PMID- 28402994
TI - Intestinal fibrosis: ready to be reversed.
AB - PURPOSE OF REVIEW: Intestinal fibrosis is a common complication of several
enteropathies, with inflammatory bowel disease (IBD) being the major cause.
Intestinal fibrosis affects both ulcerative colitis and Crohn's disease, and no
specific antifibrotic therapy exists. This review highlights recent developments
in this area. RECENT FINDINGS: The pathophysiology of intestinal stricture
formation includes inflammation-dependent and inflammation-independent
mechanisms. A better understanding of the mechanisms of intestinal fibrogenesis
and the availability of compounds for other nonintestinal fibrotic diseases bring
clincial trials in stricturing Crohn's disease within reach. SUMMARY: Improved
understanding of its mechanisms and ongoing development of clinical trial
endpoints for intestinal fibrosis will allow the testing of novel antifibrotic
compounds in IBD.
PMID- 28402999
TI - Clinical Application and the Free Posterior Thigh Perforator Flap.
AB - OBJECTIVE: The posterior thigh region has been neglected as a donor site for free
perforator flaps, likely due to difficulties in positioning the patient during
surgery. This study describes the clinical application of the posterior thigh
perforator flap based on the third perforating artery of the profunda femoris
artery (PFA). METHODS: The free posterior thigh perforator flap based on the
third perforating artery of the PFA was used for reconstruction of soft tissue
defects in nine patients between February 2010 and May 2014. RESULTS: Flap sizes
ranged from 12 * 7 cm to 20 * 13 cm. The length of the vascular pedicle averaged
10.28 cm, and the mean diameters of the third perforating artery and venae
comitantes were 1.68 and 1.14 mm, respectively. All of the perforators originated
from the PFA. Of the 9 free flaps used in 9 patients, 7 flaps survived
completely. There were no early complications in these flaps. During the follow
up period, no patient experienced cold intolerance, scar contracture, or scar
pain. There were no functional impairments at the donor or recipient sites.
CONCLUSIONS: The posterior thigh flap based on the third perforating artery of
the PFA is an excellent option for reconstructing soft tissue defects. The
anatomical location of the third perforating artery is relatively consistent. The
vascular pedicle is relatively longer and has large caliber vessels. The scar at
the donor site can be well concealed with low morbidity. The skin color and
texture of this flap show satisfactory results.
PMID- 28403000
TI - The Combined Use of a Neurocutaneous Flap and the Ilizarov Technique for
Reconstruction of Large Soft Tissue Defects and Bone Loss in the Tibia.
AB - BACKGROUND: Management of posttraumatic large soft tissue defects and bone loss
remains a therapeutic and surgical challenge for orthopedic surgeons. We assessed
the use of a neurocutaneous flap and the Ilizarov technique in the reconstruction
of severe composite defects in the tibia. METHODS: We retrospectively reviewed 18
consecutive patients with trauma-related soft tissue defects and bone loss. The
size of the soft tissue defect ranges from 8 * 9 cm to 14 * 18 cm. The mean size
of bone loss was 4.5 cm. A great saphenous neurocutaneous flap or sural
neurocutaneous flap was created to reconstruct the soft tissue defect. The
Ilizarov external fixator was applied to reconstruct bony loss by means of
distraction osteogenesis. RESULTS: The mean follow-up period was 38.8 months. All
transferred flaps survived completely. The area covered ranged from 9 * 10 cm to
15 * 20 cm. The mean distraction length and duration of use of the external
fixator were 6 cm and 11.4 months, respectively. All patients achieved final
union. Complications of superficial pin-tract infections and mild Achilles tendon
contracture were observed, but these were resolved over time. All patients were
satisfied with the outcome of the surgery. CONCLUSIONS: A well-vascularized
neurocutaneous flap is a safe and effective option in lower extremity
reconstruction under a stable mechanical environment, which can be created using
the Ilizarov technique. It is a good option for reconstructing severe complex
defects in the lower limb.
PMID- 28403001
TI - Lateral Thoracodorsal Flap or Lateral Intercostal Artery Perforator Flap: What Is
in the Name?
PMID- 28403002
TI - Lateral Intercostal Perforator Flap Letter Response.
PMID- 28403003
TI - Levels of Evidence in Medical Research: "Bigger Is Not Always Better".
PMID- 28403004
TI - The Hidden Value of Narrative Comments for Assessment: A Quantitative Reliability
Analysis of Qualitative Data.
AB - PURPOSE: In-training evaluation reports (ITERs) are ubiquitous in internal
medicine (IM) residency. Written comments can provide a rich data source, yet are
often overlooked. This study determined the reliability of using variable amounts
of commentary to discriminate between residents. METHOD: ITER comments from two
cohorts of PGY-1s in IM at the University of Toronto (graduating 2010 and 2011; n
= 46-48) were put into sets containing 15 to 16 residents. Parallel sets were
created: one with comments from the full year and one with comments from only the
first three assessments. Each set was rank-ordered by four internists external to
the program between April 2014 and May 2015 (n = 24). Generalizability analyses
and a decision study were performed. RESULTS: For the full year of comments,
reliability coefficients averaged across four rankers were G = 0.85 and G = 0.91
for the two cohorts. For a single ranker, G = 0.60 and G = 0.73. Using only the
first three assessments, reliabilities remained high at G = 0.66 and G = 0.60 for
a single ranker. In a decision study, if two internists ranked the first three
assessments, reliability would be G = 0.80 and G = 0.75 for the two cohorts.
CONCLUSIONS: Using written comments to discriminate between residents can be
extremely reliable even after only several reports are collected. This suggests a
way to identify residents early on who may require attention. These findings
contribute evidence to support the validity argument for using qualitative data
for assessment.
PMID- 28403005
TI - Impact of Patient Affect on Physician Estimate of Probability of Serious Illness
and Test Ordering.
AB - PURPOSE: The authors hypothesize patient facial affect may influence clinician
pretest probability (PTP) estimate of cardiopulmonary emergency (CPE) and desire
to order a computerized tomographic pulmonary angiogram (CTPA). METHOD: This
prospective study was conducted at three Indiana University-affiliated hospitals
in two parts: collecting videos of patients undergoing CTPA for suspected acute
pulmonary embolism watching a humorous video (August 2014-April 2015) and
presenting the medical histories and videos to clinicians to determine the impact
of patient facial affect on physicians' PTP estimate of CPE and desire to order a
CTPA (June-November 2015). Patient outcomes were adjudicated as CPE+ or CPE- by
three independent reviewers. Physicians completed a standardized test of facial
affect recognition, read standardized medical histories, then viewed videos of
the patients' faces. Clinicians marked their PTP estimate of CPE and desire for a
CTPA before and after seeing the video on a visual analog scale (VAS). RESULTS:
Fifty physicians completed all 73 videos. Seeing the patient's face produced a >
10% absolute change in PTP estimate of CPE in 1,204/3,650 (33%) cases and desire
for a CTPA in 1,095/3,650 (30%) cases. The mean area under the receiver operating
characteristic curve for CPE estimate was 0.55 +/- 0.15, and the change in CPE
VAS was negatively correlated with physicians' standardized test scores (r =
0.23). CONCLUSIONS: Clinicians may use patients' faces to make clinically
important inferences about presence of serious illness and need for diagnostic
testing. However, these inferences may fail to align with actual patient
outcomes.
PMID- 28403007
TI - Evidence-Based Scar Management: How to Improve Results with Technique and
Technology.
PMID- 28403008
TI - A New Design for Reconstruction of Nasal Dimensions during the Primary Repair of
Unilateral Cleft Lip.
PMID- 28403009
TI - Obstructive Sleep Apnea in Adults: The Role of Upper Airway and Facial Skeletal
Surgery.
PMID- 28403010
TI - Prevention of metabolic diseases: fruits (including fruit sugars) vs. vegetables.
AB - PURPOSE OF REVIEW: To discuss recent evidence from observational and intervention
studies on the relationship between fruit and vegetable (F&V) consumption and
metabolic disease. RECENT FINDINGS: Observational studies have consistently
demonstrated a modest inverse association between the intake of fruit and leafy
green vegetables, but not total vegetables, and biomarkers of metabolic disease
as well as incident type 2 diabetes mellitus. This is in contrast to limited
evidence from recently published randomized controlled dietary intervention
trials, which - in sum - suggests little to no impact of increased F&V
consumption on biomarkers of metabolic disease. SUMMARY: Evidence from
observational studies that fruit and leafy green vegetable intake is associated
with lower type 2 diabetes risk and better metabolic health could not be
confirmed by dietary intervention trials. It is unclear whether this discrepancy
is because of limitations inherent in observational studies (e.g., subjective
dietary assessment methods, residual confounding) or due to limitations in the
few available intervention studies (e.g., short duration of follow-up,
interventions combining whole fruit and fruit juice, or lack of compliance).
Future studies that attempt to address these limitations are needed to provide
more conclusive insight into the impact of F&V consumption on metabolic health.
PMID- 28403011
TI - Emerging roles of lipid metabolism in cancer progression.
AB - PURPOSE OF REVIEW: Lipid metabolism in cancer cells and tumor-associated stromal
cells was recently identified to contribute to disease progression particularly
in response to changes in tumor microenvironment such as acidosis and hypoxia.
RECENT FINDINGS: New molecular mechanisms driving lipid metabolism in various
cancers were elicited through genetic silencing, pharmacological inhibition of
key metabolic enzymes, including those involved in fatty acid oxidation and
synthesis, and modulation of diet composition. SUMMARY: To proliferate,
metastasize, or resist stress conditions imposed by the microenvironment, many
cancer cells rely on fatty acid beta-oxidation to generate acetyl-CoA and fuel
the TCA cycle, and on fatty acid synthesis to produce building blocks. These
processes are fine-tuned through regulation of acetyl-CoA carboxylases expression
and activity. Stromal cells including lymphocytes, (lymphatic) endothelial cells
and adipocytes also participate through either fatty acid transfer or lipid-based
signaling to cancer disease progression. Altogether, these data identify critical
nodes in the orchestration of lipid metabolism in cancer that may facilitate the
design of synthetic-lethal treatments.
PMID- 28403012
TI - Can Vertical Integration Reduce Hospital Readmissions? A Difference-in
Differences Approach.
AB - BACKGROUND: Vertical integration is expected to improve communication and
coordination between inpatient care and care after discharge. Despite being used
across health systems worldwide, evidence about its impact on readmissions is
sparse and contradictory. OBJECTIVE: To assess the impact of vertical integration
on hospital readmissions. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Using
difference-in-differences we compared readmissions before and after vertical
integration in 6 Portuguese hospitals for years 2004-2013. A control group with 6
similar hospitals not integrated was utilized. Considered outcome was 30-day
unplanned readmission. We used logistic regression at the admission level and
accounted for patients' risk factors using claims data. Analyses for each
hospital and selected conditions were also run. RESULTS: Our results suggest that
readmissions decreased overall after vertical integration [odds ratio (OR)=0.900;
95% confidence interval (CI), 0.812-0.997]. Hospital analysis indicated that
there was no impact for 2 hospitals (OR=0.960; 95% CI, 0.848-1.087 and OR=0.944;
95% CI, 0.857-1.038), and a positive effect in 4 hospitals (greatest effect:
OR=0.811; 95% CI, 0.736-0.894). A positive evolution was observed for a limited
number of conditions, with better results for diabetes with complications
(OR=0.689; 95% CI, 0.525-0.904), but no impact regarding congestive heart failure
(OR=1.067; 95% CI, 0.827-1.377). CONCLUSIONS: Merging acute and primary care
providers was associated with reduced readmissions, even though improvements were
not found for all institutions or condition-specific groups. There are still
challenges to be addressed regarding the success of vertical integration in
reducing 30-day hospital readmissions.
PMID- 28403013
TI - Vasopressin and diabetic nephropathy.
AB - PURPOSE OF REVIEW: The prevalence of diabetic kidney disease (DKD) is increasing
worldwide. Despite major therapeutic advances in the last decades in DKD, the
current standard of care let many people progress to severe stages. Vasopressin
secretion is increased in diabetes, and its potential role in the onset and
progression of DKD is being re-investigated. RECENT FINDINGS: Recently,
observational studies evidenced an association between surrogates of vasopressin
secretion (daily fluid intake or urine volume, and plasma copeptin concentration)
and chronic kidney disease in the community, but also specifically in type 1 and
in type 2 diabetes. Causality is strongly supported by a series of studies in
rats conducted more than a decade ago, and by additional recent experimental
data. The mechanism underlying these adverse effects likely involves the
hyperfiltration induced indirectly as a consequence of the tubular effects of the
hormone mediated by the V2 receptor. SUMMARY: If chronic vasopressin action on
the kidney is detrimental in diabetes as suggested so far, intervention studies
should be designed. Available tools include V2 receptor blockade, and changes in
daily water intake in vulnerable patients. Safety and effectiveness should be
tested, as it is currently done in patients with CKD (NCT01766687).
PMID- 28403014
TI - Occupational exposures and genetic susceptibility to urinary tract cancers: a
systematic review and meta-analysis.
AB - This study aims to summarize the current knowledge on the relationship between
genetic polymorphisms, occupational exposures, and urinary tract cancers. We
searched MEDLINE, ISI Web of science, and SCOPUS online databases for all
articles published in English language up to September 2016. A meta-analysis was
performed to provide summary estimates for the association between a certain
genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney
cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed
eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07
[95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07
(95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed
to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR
of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of
2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide
exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1
present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype
and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1
active genotypes. This meta-analysis indicates a possible association between the
variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to
aromatic amines or PAHs, and development of BC. Our results suggest that
polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC
in individuals occupationally exposed to pesticides.
PMID- 28403015
TI - HR-HPV E6/E7 mRNA In Situ Hybridization: Validation Against PCR, DNA In Situ
Hybridization, and p16 Immunohistochemistry in 102 Samples of Cervical, Vulvar,
Anal, and Head and Neck Neoplasia.
AB - Dysregulated expression of oncogenic types of E6 and E7 is necessary for human
papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ
hybridization (ISH) assay covering 18 common high-risk types ("HR-RISH," aka HR
HPV RNA18 ISH) has not been extensively studied in the anogenital tract or
validated on automated technology. We herein compare HR-RISH to DNA polymerase
chain reaction (PCR), p16 immunohistochemistry, and a previously available HPV
DNA ISH assay in HPV-related anogenital and head and neck (H&N) neoplasia. A
total of 102 squamous intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3,
9 VIN3)/invasive squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well
as 10 normal and 15 reactive cervix samples were collected. HR-RISH, DNA ISH, and
p16 immunohistochemistry were performed on whole formalin-fixed, paraffin
embedded sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed.
RNA and DNA ISH assays used automated systems. HR-HPV PCR was performed on
morphology-directed formalin-fixed, paraffin-embedded punches. HR-RISH was >=97%
sensitive for PCR+ and p16+ neoplasia, as well as morphologically defined
anogenital high grade squamous intraepithelial lesion/invasive squamous cell
carcinoma. HR-RISH was also positive in 78% of anogenital low grade squamous
intraepithelial lesion, including 81% of CIN1. Furthermore, a subset of PCR
negative/invalid and p16-negative lesions was positive for HR-RISH. Only 1
problematic reactive cervix sample and no normal cervix samples stained. These
results demonstrate that HR-RISH is a robust method for the detection of HR-HPV
related neoplasia and provides insight into HPV pathobiology. Performance meets
or exceeds that of existing assays in anogenital and H&N lesions and may play a
role in resolving diagnostically challenging CIN1 versus reactive cases.
PMID- 28403016
TI - Green Collar Workers: An Emerging Workforce in the Environmental Sector.
AB - OBJECTIVE: We describe the socio-demographic, occupational, and health
characteristics of "green collar" workers, a vital and emerging workforce in
energy-efficiency and sustainability. METHODS: We linked data from the 2004 to
2012 National Health Interview Surveys (NHIS) and US Occupational Information
Network (O*NET). Descriptive and logistic regression analyses were conducted
using green collar worker status as the outcome (n = 143,346). RESULTS: Green
collar workers are more likely than non-green workers to be men, age 25 to 64
years, obese, and with less than or equal to high school (HS) education. They are
less likely to be racial/ethnic minorities and employed in small companies or
government jobs. CONCLUSIONS: Green collar workers have a distinct socio
demographic and occupational profile, and this workforce deserves active
surveillance to protect its workers' safety. The NHIS-O*NET linkage represents a
valuable resource to further identify the unique exposures and characteristics of
this occupational sector.
PMID- 28403017
TI - Effects of different fresh gas flows with or without a heat and moisture
exchanger on inhaled gas humidity in adults undergoing general anaesthesia: A
systematic review and meta-analysis of randomised controlled trials.
AB - BACKGROUND: The minimum inhaled gas absolute humidity level is 20 mgH2O l for
short-duration use in general anaesthesia and 30 mgH2O l for long-duration use in
intensive care to avoid respiratory tract dehydration. OBJECTIVE: The aim is to
compare the effects of different fresh gas flows (FGFs) through a circle
rebreathing system with or without a heat and moisture exchanger (HME) on inhaled
gas absolute humidity in adults undergoing general anaesthesia. DESIGN:
Systematic review and meta-analyses of randomised controlled trials. We defined
FGF (l min) as minimal (0.25 to 0.5), low (0.6 to 1.0) or high (>=2). We
extracted the inhaled gas absolute humidity data at 60 and 120 min after
connection of the patient to the breathing circuit. The effect size is expressed
as the mean differences and corresponding 95% confidence intervals (CI). DATA
SOURCES: PubMed, EMBASE, SciELO, LILACS and CENTRAL until January 2017. RESULTS:
We included 10 studies. The inhaled gas absolute humidity was higher with minimal
flow compared with low flow at 120 min [mean differences 2.51 (95%CI: 0.32 to
4.70); P = 0.02] but not at 60 min [mean differences 2.95 (95%CI: -0.95 to 6.84);
P = 0.14], and higher with low flow compared with high flow at 120 min [mean
differences 7.19 (95%CI: 4.53 to 9.86); P < 0.001]. An inhaled gas absolute
humidity minimum of 20 mgH2O l was attained with minimal flow at all times but
not with low or high flows. An HME increased the inhaled gas absolute humidity:
with minimal flow at 120 min [mean differences 8.49 (95%CI: 1.15 to 15.84); P =
0.02]; with low flow at 60 min [mean differences 9.87 (95%CI: 3.18 to 16.57); P =
0.04] and 120 min [mean differences 7.19 (95%CI: 3.29 to 11.10); P = 0.003]; and
with high flow of 2 l min at 60 min [mean differences 6.46 (95%CI: 4.05 to 8.86);
P < 0.001] and of 3 l min at 120 min [mean differences 12.18 (95%CI: 6.89 to
17.47); P < 0.001]. The inhaled gas absolute humidity data attained or were near
30 mgH2O l when an HME was used at all FGFs and times. CONCLUSION: All intubated
patients should receive a HME with low or high flows. With minimal flow, a HME
adds cost and is not needed to achieve an appropriate inhaled gas absolute
humidity.
PMID- 28403018
TI - Prophylactic atropine administration attenuates the negative haemodynamic effects
of induction of anaesthesia with propofol and high-dose remifentanil: A
randomised controlled trial.
AB - BACKGROUND: Induction of anaesthesia with propofol and remifentanil often induces
unwanted bradycardia and hypotension, raising concerns regarding tissue
oxygenation. The electrophysiological cardiac effects of remifentanil can be
reversed by atropine. OBJECTIVE: To investigate if prophylactic administration of
atropine can attenuate the negative haemodynamic effects of propofol and a high
dose of remifentanil during induction of anaesthesia. DESIGN: A double-blind,
randomised controlled trial. SETTING: Single-centre, University Medical Center
Groningen, The Netherlands. PATIENTS: Sixty euvolaemic patients scheduled for
surgery under general anaesthesia. INTERVENTIONS: Anaesthesia was induced and
maintained with a target-controlled infusion of propofol with a target effect
site concentration (Ce) of 2.5 MUg ml, remifentanil (target-controlled infusion),
(Ce 8 ng ml) and cis-atracurium. Methylatropine (500 MUg) or 0.9% saline was
administered at immediately before induction of anaesthesia. MAIN OUTCOME
MEASURES: The changes (Delta) in mean arterial pressure (MAP), heart rate (HR),
cardiac index (CI), rate pressure product, cerebral tissue oxygenation and
peripheral tissue oxygenation between induction of anaesthesia (T0) and 10 min
later (T10). RESULTS: Atropine significantly attenuated the changes in the
outcome measures between T0 and T10. Median (inter-quartile range) changes were
MAP, Delta = -24 (-40 to -21) vs. Delta = -37 mmHg (-41 to -31) (P = 0.02); HR,
Delta = 0 +/- 13 vs. -19 +/- 11 bpm (P < 0.01); CI, Delta = -0.4 +/- 0.7 vs. -0.9
+/- 0.6l min m (P < 0.01) and rate pressure product, Delta = -3241 (-5015 to
613) vs. Delta = -5712 mmHg min (-6715 to -3917) (P < 0.01). Cerebral tissue
oxygenation and peripheral tissue oxygenation did not change in either group.
Maximum HR after atropine was 102 (86 to 116) vs. 85 bpm (76 to 95). CONCLUSION:
Administration of atropine, before induction of anaesthesia with propofol and
high-dose remifentanil, can significantly reduce the decreases in HR, MAP and CI.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01871922.
PMID- 28403019
TI - Food labeling issues in patients with severe food allergies: solving a hamlet
like doubt.
AB - PURPOSE OF REVIEW: We review the laws on labeling in the international community,
the difficulties they pose to the food manufacturers to prepare the food labels
and the methodologies to determine the concentration of potential allergens in
foods. RECENT FINDINGS: European Food Safety Authority and International Life
Sciences Institute Europe are evaluating strategies to identify the threshold
level of allergen that can trigger a reaction in individuals. The most used
techniques to detect the presence of protein in food are Enzyme-linked
immunosorbent assay, polymerase chain reaction and real time polymerase chain
reaction. Researchers are now trying to apply proteomics to estimate the amount
of protein within the food.In order to protect the health of consumers, the Codex
Alimentarius Commission updates constantly the list of allergens. In response to
these regulations, some industries have also added some precautionary allergen
labeling (PAL). It was generally agreed that PAL statements needed to be visible,
simple, and safe. It was suggested that PAL be standardized, an action that would
occur if the 'Voluntary Incidental Trace Allergen Labelling' process was made
mandatory. SUMMARY: So far, no laboratory technique is able to reassure the
consumers about the composition of foods found on the packaging. International
authorities produced increasingly stringent laws, but more is still to do.
PMID- 28403020
TI - Understanding the Impact of Preservation Methods on the Integrity and
Functionality of Placental Allografts.
AB - INTRODUCTION: Human placental membranes (hPMs) have a long history in treating
burns and wounds. The composition of hPMs includes structural matrix, growth
factors, and neonatal cells, all of which contribute to their regenerative
potential. However, most hPM products are devitalized after dehydration and
irradiation. We compared the functionality of single-layer viable cryopreserved
human amniotic membrane (vCHAM) with multilayer devitalized dehydrated human
amnion/chorion membrane (dHACM) in wound-relevant models to determine the effect
of different processing methods on hPMs. METHODS: Viable cryopreserved human
amniotic membrane and dHACM were compared with fresh hPM for structural integrity
and viability. Viable cell persistence in vCHAM over time was evaluated in vitro
and in vivo in a diabetic chronic wound mouse model. Proliferation of cells
within fresh hPM and vCHAM was evaluated with bromodeoxyuridine and Ki-67
staining, and proliferation of isolated cells in culture was evaluated. Growth
factor release over time and in vitro response to chronic wound stimuli (tumor
necrosis factor alpha, lipopolysaccharide, and hypoxia) were used to compare the
functionality of vCHAM and dHACM. RESULTS: The structure and thickness of fresh
hPM were retained in vCHAM but were compromised in dHACM. Similar to fresh hPM,
vCHAM contained viable cells, whereas dHACM did not. Cells in vCHAM remained
viable after 4 and 7 days in culture and in an in vitro chronic wound environment
and after 4 and 8 days in vivo after application to a mouse chronic wound.
Staining for bromodeoxyuridine and Ki-67 did not reveal proliferative cells
within fresh hPM and vCHAM. However, isolated cells proliferated in culture.
Viable cryopreserved human amniotic membrane increased platelet-derived growth
factor BB, hepatocyte growth factor, and epidermal growth factor levels over time
and responded to chronic wound stimuli in vitro by significantly increasing
levels of vascular endothelial growth factor and prostaglandin E2. Dehydrated
human amnion/chorion membrane showed no significant accumulation of growth
factors and did not respond to chronic wound stimuli. CONCLUSIONS: These results
indicate that vCHAM retains intact, native matrix, and viable, active cells and
responds to chronic wound stimuli in vitro. The inclusion of multiple layers of
hPM does not compensate for structural degradation and loss of viability caused
by dehydration as evidenced by a lack of functional response by dHACM. The
clinical significance of these results remains to be answered.
PMID- 28403021
TI - Distally Based Medial Hemisoleus Muscle Flap: Anatomic and Angiographic Study of
18 Lower Limbs.
AB - BACKGROUND: The distally based medial hemisoleus (MHS) flap was found useful for
repairing soft-tissue defects of the lower third of the leg; however, its
reliability is controversial. We used a combination of static and dynamic
techniques to investigate the vascular supply of distally based MHS muscle flaps
to better establish their use in repair of lower-third leg defects. METHODS: We
performed an anatomic study of 18 cadaver legs. For 6 legs, we performed dynamic
angiography, which allowed for obtaining MHS muscle radiographs after pulsed
injection of contrast medium in distal pedicles. RESULTS: The mean length of MHS
muscle was 25.4 cm, the mean width was 6.9 cm, and the mean surface area was 87.5
cm. A mean of 3 distal posterior tibial vascular pedicles was directly connected
to this medial subunit. These pedicles were present in all 18 cadaver legs. We
observed complete opacification of the 6 MHS muscles through distal pedicles.
Radiography revealed opacification of a vascular path from 1 distal pedicle to 1
proximal vascular pedicle of the MHS muscle. The mean level of this main distal
pedicle was 14.5 cm to the tip of the medial malleolus. The level was at 38.2%,
on average, from the bottom of the entire tibia. CONCLUSIONS: The distally based
MHS muscle flap has constant blood supply, so it could be a useful flap to repair
soft-tissue defects of the lower third of the leg. Moreover, knowledge of the
average location of the main distal pedicle can help in increasing the use of the
distally based MHS flap.
PMID- 28403022
TI - The Sternum-Nipple Distance is Double the Nipple-Inframammary Fold Distance in
Macromastia.
AB - BACKGROUND: Reduction mammaplasty is one of the most commonly performed plastic
surgery operations. For a majority of techniques, the most common long-term
complication is pseudoptosis. It has previously been proposed that upper breast
suspensory ligaments (SL) are weaker than lower breast SL. We tested this
hypothesis through anthropometry of the proxies for upper and lower SL strength:
the sternal notch-nipple (SN-N) distance and the nipple-inframammary fold (N-IMF)
distance, respectively. METHODS: An institutional review board-approved
retrospective review of patients undergoing reduction mammoplasty in an academic
faculty practice between 2008 and 2015 was conducted. Patient demographics
included age, race, and body mass index (BMI); patient comorbidities included
smoking status, diabetes, and hypertension. Breast anthropometric measurements
included SN-N and N-IMF. Sternal notch-nipple was used as the primary metric of
the upper SL strength, whereas N-IMF was used as the primary metric of the lower
SL strength. Intraoperative details included reduction technique and resection
mass. Postoperative complications were recorded, including nipple areola complex
necrosis and hematoma. Linear regression analysis was performed with the primary
endpoint of the relationship between SN-N and N-IMF distance in macromastia.
RESULTS: Data from 208 patients, totaling 400 individual breast measurements,
were collected. The mean SN-N length was 35.1 cm, mean N-IMF length was 16.0 cm,
and mean resection weight was 1094 g. Linear regression found that N-IMF distance
could be predicted as 45% of the SN-N distance (N-IMF = 0.454 * SN-N). This was a
strong relationship, demonstrated by univariate analysis of SN-N and N-IMF (R,
0.624; P < 0.001). A Wise pattern was used in 89.9% of cases; an inferior pedicle
was used in 83.7% of cases. Nipple areola complex necrosis occurred in 15 breasts
(3.75%). Sternal notch-nipple (R, 0.127; P = 0.011) and N-IMF (R, 0.119; P =
0.017) were both predictive of nipple areola complex necrosis (Table 4).
CONCLUSIONS: In our series, the N-IMF distance increased 0.45 cm for every 1 cm
increase in the SN-N distance. This relationship strengthens our primary
hypothesis that the lower pole ligaments stretch at a significantly slower rate
than the upper pole ligaments. Taking this into consideration, we suggest that
surgeons seeking to minimize pseudoptosis rates should favor techniques that
minimally disrupt the lower SL.
PMID- 28403024
TI - Multimodal Hyperspectroscopic Imaging for Detection of High-Grade Cervical
Intraepithelial Neoplasia.
AB - OBJECTIVE: Numerous new alternative digital colposcopy techniques have been
developed, of which multimodal hyperspectroscopy (MHS) showed a high sensitivity
in previous studies. The objective of this prospective single-center cohort study
was to evaluate the clinical value of MHS for detecting high-grade cervical
intraepithelial neoplasia in a colposcopy referral population and colposcopy
follow-up population, to assess whether MHS could be safely used to improve care
for women at risk for high-grade cervical intraepithelial neoplasia. MATERIALS
AND METHODS: A total of 125 women from a colposcopy referral population and
colposcopy follow-up population were evaluated with MHS and tested for the
presence of high-risk human papillomavirus (HPV) with HPV-16/18 genotyping.
Spectroscopic measurements of the cervix were taken and compared with an end
point based on histology, high-risk HPV, and cytology. Evaluable data for
analysis were collected from 102 of the subjects. Sensitivity, specificity, and
predictive values were calculated for MHS and colposcopic impression based on
conventional colposcopic examination. RESULTS: From the total study population of
the 102 patients, 47 were enrolled in the colposcopy referral group and 55 in the
colposcopy follow-up group. The MHS yielded a sensitivity of 93.6% (95% CI = 78.6
99.2), with a corresponding specificity of 42.3% (95% CI = 30.6-54.6) in the
group with a composite end point. No adverse effects occurred, and patient
acceptability was high. CONCLUSIONS: Multimodal hyperspectroscopy is a digital
colposcopy technique that offers an easy, rapid, well-tolerated point-of-care
assessment with a high sensitivity for the presence of high-grade cervical
intraepithelial lesions, however, with a low specificity, resulting in limited
clinical value.
PMID- 28403025
TI - p16INK4a, Cytokeratin 7, and Ki-67 as Potential Markers for Low-Grade Cervical
Intraepithelial Neoplasia Progression.
AB - OBJECTIVE: The aim of this study was to evaluate p16, cytokeratin 7 (CK7), and Ki
67 immunoexpressions in low-grade squamous intraepithelial lesion (LSIL), looking
for differences among cases that progress to high-grade squamous intraepithelial
lesion, maintain LSIL, or regress. MATERIALS AND METHODS: Sixty-six LSIL biopsies
were studied. In the follow-up, a second biopsy showed 28.7% regression, 37.9%
LSIL, and 33.4% progressed to high-grade squamous intraepithelial lesion.
Immunostaining for these markers were performed in the first biopsy. A
qualitative evaluation method was used, as well as histomorphometry, using ImageJ
software. Pearson chi, Mann-Whitney, Kruskal-Wallis, and Fisher tests were used
to compare the groups (P <= .05). A cutoff point was assessed through receiver
operating characteristic curve positive cell ratio, for each marker, as
progression predictors. RESULTS: The mean age of patients with and without
progression was 33 and 27 years (P = .006), respectively. The qualitative
evaluation indicated a tendency of progression, but without statistical
significance. However, through histomorphometry, the receiver operating
characteristic curve analysis showed cutoff points of 0.396, 0.345, and 0.026 for
p16, CK7, and Ki-67 ratios, respectively, as predictors of progression (P = .003,
.03, and .002, respectively). In a logistic regression analysis, p16, CK7, and Ki
67 positive cell ratio showed a significant correlation with progression (P =
.036, .012, and .006, respectively). CONCLUSIONS: p16, CK7, and Ki-67 may
represent useful biomarkers that can identify LSIL lesions that need particular
attention.
PMID- 28403026
TI - Candidates for inclusion in a universal antiretroviral regimen: are lamivudine
and emtricitabine interchangeable?
AB - PURPOSE OF REVIEW: Lamivudine (3TC) and emtricitabine (FTC) are the most widely
used antiretroviral medications worldwide and are considered by the WHO to be
interchangeable. This article reviews evidence supporting interchangeability of
3TC and FTC and considerations for future use. RECENT FINDINGS: Three randomized
trials have directly compared the safety and efficacy of 3TC and FTC against
identical backbone regimens. Each of these trials reported a nonsignificant
difference in virological suppression, and when results were pooled the overall
difference was nonsignificant (relative risk 1.03, 95% confidence interval 0.96
1.10). These findings of equivalence are further supported by indirect evidence
from nine randomized trials comparing 3TC and FTC against a similar backbone
regimen of two different nucleoside reverse transcriptase inhibitors (relative
risk of virological suppression 0.99, 95% confidence interval 0.96-1.01). Data
from observational studies is mixed. Overall, reported differences between 3TC
and FTC in observational studies are often associated with differences in the
baseline characteristics of the treatment groups, notably with respect to
immunological and virological status, comorbidity, substance misuse, and pill
burden. SUMMARY: The totality of evidence to date, from pharmacological data to
observational studies to direct and indirect comparisons in randomized trials,
suggests that 3TC and FTC can be considered to be therapeutically interchangeable
and that if there are any differences, these are likely to be very small and not
of major clinical importance.
PMID- 28403027
TI - Candidates for inclusion in a universal antiretroviral regimen: tenofovir
alafenamide.
AB - PURPOSE OF REVIEW: Tenofovir disoproxil fumarate (TDF) is a standard first-line
therapy for HIV. Recently, tenofovir alafenamide (TAF), a different prodrug for
the same active moiety, has been approved. In this review, we have conducted a
meta-analysis comparing efficacy and safety data for TDF and TAF, to inform a
discussion of which drug would be best for a proposed 'universal antiretroviral
(ARV) regimen'. RECENT FINDINGS: We identified 10 randomized controlled trials
comparing TDF with TAF (6969 patients, 8043 patient-years of follow-up). Meta
analysis found no difference in treatment efficacy, resistance, or adverse
events. There were significant differences favouring TAF in bone mineral density
measures and renal function measures, but no significant difference in bone
fracture events or discontinuations because of bone toxicity or renal toxicity.
TAF arms showed higher lipid levels, and were associated with a slightly greater
risk of being started on lipid-lowering therapy. SUMMARY: TAF has lesser
detrimental effects on renal and bone markers, but no difference in adverse
events. Data are unavailable for TAF safety in pregnancy, tuberculosis
coinfection, and low CD4 count. Data for these groups, and an affordable price,
will be required before it can be recommended as part of a 'universal ARV
regimen'.
PMID- 28403028
TI - Compatibility of next-generation first-line antiretrovirals with rifampicin-based
antituberculosis therapy in resource limited settings.
AB - PURPOSE OF REVIEW: Reduced dose efavirenz, dolutegravir, and/or tenofovir
alafenamide (TAF) are likely to be used in the next generation of first-line
antiretroviral therapy in resource limited settings, where HIV-associated
tuberculosis is common. Rifampicin, which is a key component of first-line
antituberculosis therapy, is a potent inducer of many drug transporters and
metabolising enzymes. We reviewed the literature for potential or actual drug-
drug interactions between these antiretrovirals and rifampicin. RECENT FINDINGS:
Dose adjustments of standard dose efavirenz are not necessary with rifampicin,
because auto-induction of CYP2B6 by efavirenz counteracts the induction of
rifampicin. However, patients with extensive metabolizer CYP2B6 genotypes have
lower efavirenz concentrations and may have less auto-induction of CYP2B6; the
additive inducing effects of rifampicin on CYP2B6 could result in clinically
significant reductions of efavirenz concentrations. Doubling the dose of
dolutegravir overcomes induction by rifampicin. TAF is more prone to be the
victim in drug--drug interactions than tenofovir disoproxil fumarate.
Interactions between TAF and rifampicin have not been studied, but there is
likely to be significant interaction. SUMMARY: Further research on drug--drug
interactions between rifampicin and the next generation of first-line
antiretrovirals will be needed before they can be recommended in patients with
HIV-associated tuberculosis.
PMID- 28403029
TI - Secular Trends in the Physical Fitness of United States Army Recruits on Entry to
Service, 1975-2013.
AB - Knapik, JJ, Sharp, MA, and Steelman, RA. Secular trends in the physical fitness
of United States Army recruits on entry to service, 1975-2013. J Strength Cond
Res 31(7): 2030-2052, 2017-A systematic literature search was conducted to
identify and analyze articles that reported on physical fitness of new US Army
recruits. The National Library of Medicine's PubMed and the Defense Technical
Information Center were searched using the keywords (military personnel OR
trainee OR recruit OR soldier) AND (physical fitness OR strength OR endurance OR
flexibility OR balance OR coordination OR muscle contraction OR running OR
exercise OR physical conditioning). Reference lists of obtained articles and
contact with authors enhanced the search. Studies were selected if they involved
recruits in Basic Combat Training or One-Station Unit Training, provided a
quantitative assessment of at least one fitness measure, and the fitness
measure(s) were obtained early in training. Average values for each fitness
measure were obtained, plotted by the year of data collection, and fitted to
linear regression models (fitness measure * year). Fifty-three articles met the
review criteria. Regression analysis indicated little temporal change in height,
but body weight, body mass index, body fat, and fat-free mass increased over
time. Limited V[Combining Dot Above]O2max data suggested no temporal change in
male recruits, but those in female recruits V[Combining Dot Above]O2max seem to
have slightly improved. Apparently contradicting the V[Combining Dot Above]O2max
findings, performance on endurance runs (1- and 2-mile) declined, possibly
because of the increase in body weight. Muscular endurance (push-ups, sit-ups)
demonstrated little systematic change over time. Limited but multiple measures of
muscular strength suggest a temporal increase in strength. Specific components of
US Army recruit fitness seem to have changed over time.
PMID- 28403030
TI - Keep Screening! Maternal Gonococcal Infection and Adverse Birth Outcomes.
PMID- 28403031
TI - The Sobel Distinguished Scholar in Coronary Artery Disease.
PMID- 28403032
TI - Effect of alirocumab dose increase on LDL-lowering and lipid goal attainment: is
treatment to goal the way to go?
PMID- 28403033
TI - The mechanism of microvascular obstruction in patients with acute ST-segment
elevation myocardial infarction: new light from optical coherence tomography.
PMID- 28403034
TI - National Study of Off-label Proton Pump Inhibitor Use Among New Zealand Infants
in the First Year of Life (2005-2012).
AB - OBJECTIVES: Off-label prescribing of proton pump inhibitors (PPIs) to infants to
treat symptoms attributed to gastroesophageal reflux disease (GERD) is widely
reported, despite evidence that PPIs are no more effective than placebo in
relieving those symptoms. To initiate discussion about appropriate prescribing of
these drugs for infants, we describe the characteristics of PPI use among infants
in New Zealand. METHODS: In this population-based study we used routinely
collected dispensing data to identify all children born between 2005 and 2012 who
were dispensed a government-subsidized PPI (omeprazole, lansoprazole,
pantoprazole) before their first birthday. Unique patient identifiers were used
to link administrative datasets containing patient-level demographic, dispensing,
and health information. RESULTS: In total, 22,643 children were dispensed a study
PPI before their first birthday. The prevalence of infant PPI use as a proportion
of all live births increased from 2.4% for children born in 2005 to 5.2% for
children born in 2012. Overall, 71.6% of infants were dispensed a PPI by 3 months
of age, and 8.7% received a PPI within the first month of life. Before PPI
initiation, only 7.0% of infants had a hospital-based diagnosis of GERD (with or
without esophagitis), and 4.7% of infants had a hospital-based diagnosis of one
or more known or suspected GERD risk factors. CONCLUSIONS: Off-label prescribing
of PPIs to New Zealand infants was relatively common and increased over the study
period. The appropriateness of PPI treatment should be questioned, as the
majority of infants who received these drugs were not diagnosed with severe GERD.
PMID- 28403035
TI - Characterizing and Defining "Infantile Liver Failure".
PMID- 28403037
TI - Characteristics of Submacular Hemorrhages in Age-Related Macular Degeneration.
AB - PURPOSE: The aims of this research are to report the incidence and
characteristics of submacular hemorrhage secondary to neovascular age-related
macular degeneration (AMD) and to compare the detailed morphologic features of
hemorrhages between typical neovascular AMD and polypoidal choroidal vasculopathy
(PCV). METHODS: This retrospective observational study included 791 eyes of 791
patients who had newly diagnosed neovascular AMD at a single institution. The
incidence and extent of submacular hemorrhage of one disc area or greater were
estimated and compared between typical neovascular AMD and PCV. In addition,
submacular hemorrhages were classified into groups according to location
(location of fovea at the center of the hemorrhage versus at the periphery of the
hemorrhage) and morphology (circular versus irregular margin). The proportion of
each subtype of neovascular AMD was evaluated according to the aforementioned
classification. RESULTS: Among those included, 129 (16.3%) eyes exhibited
submacular hemorrhage at initial presentation. Among the 627 eyes with available
indocyanine green angiography findings, the incidence of submacular hemorrhage
was greater in PCV (23.6%, 78 of 330 eyes) than in typical neovascular AMD (9.4%,
28 of 297 eyes; chi test, P < .001). When divided into four groups according to
hemorrhage shape and location (central and circular, central and irregular,
peripheral and circular, and peripheral irregular), the proportion of eyes in
these groups was significantly different between the two disease groups (chi
test, P = .018). CONCLUSIONS: The incidence of submacular hemorrhage was greater
in PCV than in typical neovascular AMD. The morphology and location of submacular
hemorrhage may provide useful clues to differentiate PCV from typical neovascular
AMD.
PMID- 28403039
TI - Pneumotoxicity associated with immune checkpoint inhibitor therapies.
AB - PURPOSE OF REVIEW: Immune checkpoint inhibitor therapies represent a new paradigm
in cancer therapeutics, in which the targets are not the cancer cells, but the
body's own immune system. Harnessing the immune system to better fight cancer has
generated a unique spectrum of immune-related adverse events (IrAEs) that effect
virtually every major organ system. Although lung involvement is less common than
other forms of IrAEs, its consequences are potentially lethal. This review
focuses on the evolving spectrum of lung toxicities associated with the two major
classes of immune checkpoint inhibitor therapies, cytotoxic T-cell ligand-4, and
programed cell death-1 (PDL-1). RECENT FINDINGS: Lung injury was not reported in
the earliest clinical trials of immune checkpoint inhibitors. More recent
studies, however, have described unique radiographic and clinical toxicity
profiles that differ significantly from lung injury patterns associated with
conventional cytotoxic therapies. The pathophysiologic mechanisms of immune
related lung injury, its radiographic and clinical disease spectrum, associated
risk factors, and optimal treatment strategies remain poorly understood. SUMMARY:
Adverse immune-mediated lung events are increasingly recognized as unique and
potentially life-threatening sequelae of checkpoint inhibitor therapies. Early
recognition of symptoms and radiographic abnormalities is essential to proper
management and successful outcome.
PMID- 28403040
TI - Playing the odds: lung cancer surveillance after curative surgery.
AB - PURPOSE OF REVIEW: After 'curative' resection, many patients are still at risk
for further lung cancer, either as a recurrence or a new metachronous primary. In
theory, close follow-up should improve survival by catching relapse early - but
in reality, many experts feel that surveillance for recurrence is of uncertain
value. In this article, we explore the reasons behind the controversy, what the
current guidelines recommend, and what future solutions are in development that
may ultimately resolve this debate. RECENT FINDINGS: Although postoperative
surveillance for a new lung cancer may impart a survival advantage, this benefit
does not appear to extend to the phenomenon of recurrence. Nevertheless, close
radiographic follow-up after curative resection is still recommended by most
professional societies, with more frequent scanning in the first 2 years, and
then annual screening thereafter. Given the radiation risk, however, low-dose and
minimal-dose computed tomography options are under investigation, as well as
timing scans around expected peaks of recurrence rather than a set schedule.
SUMMARY: Applying the same surveillance algorithm to all lung cancer patients
after curative resection may not be cost-effective or reasonable, especially if
there is no demonstrable mortality benefit. Therefore, future research should
focus on finding safer nonradiographic screening options, such as blood or breath
biomarkers, or developing nomograms for predicting which patients will relapse
and require closer follow-up. Ultimately, however, better tools for surveillance
may be moot until we develop better treatment options for lung cancer recurrence.
PMID- 28403038
TI - Lung carcinogenesis and fibrosis taken together: just coincidence?
AB - PURPOSE OF REVIEW: The pathogenesis of lung cancer and pulmonary fibrotic
disorders partially overlaps. This review focuses on the common features of the
two disease categories, aimed at advancing our translational understanding of
their pathobiology and at fostering the development of new therapies. RECENT
FINDINGS: Both malignant and collagen-producing lung cells display enhanced
cellular proliferation, increased resistance to apoptosis, a propensity for
invading and distorting the lung parenchyma, as well as stemness potential. These
characteristics are reinforced by the tissue microenvironment and inflammation
seems to play an important adjuvant role in both types of disorders. SUMMARY:
Unraveling the thread of the common and distinct characteristics of lung fibrosis
and cancer might contribute to a more comprehensive approach of the pathobiology
of both diseases and to a pathfinder for novel and personalized therapeutic
strategies.
PMID- 28403041
TI - Sex differences in time trends of blood pressure among Swedish septuagenarians
examined three decades apart: a longitudinal population study.
AB - OBJECTIVE: The aim of this study was to analyze the influence of birth cohort,
sex and age on the trajectories of SBP and DBP in two birth cohorts of 70-year
olds, examined 3 decades apart and followed up at ages 75 and 79-80 years.
METHODS: Two population samples of 70-year-olds from Gothenburg, Sweden, were
examined. The first, born in 1901-1902, was examined in 1971-1972 (n = 973). The
second, born in 1930, was examined in 2000 (n = 509). Both samples were re
examined at ages 75 and 79-80 years. RESULTS: We found that SBP and DBP were
considerably lower in septuagenarian men and women born 1930 compared with those
born 1901-1902, also when adjusting for antihypertensive treatment in different
ways. The decline was especially pronounced in women. Blood pressure was higher
in women than in men in the 1970s, whereas there were no sex differences in the
2000s. The age-related decline in SBP started earlier and was more accentuated in
those born in 1930 than in those born in 1901-1902. CONCLUSION: Blood pressure
decreased, and the age-related decline in SBP started earlier in septuagenarians
examined in the 2000s compared with those examined in the 1970s. The decrease was
especially pronounced in women and diminished the sex differences.
Antihypertensive treatment only partly explained our findings, suggesting that
other mostly unknown factors played an important role.
PMID- 28403042
TI - Altered mitochondrial function, capacitative calcium entry and contractions in
the aorta of hypertensive rats.
AB - OBJECTIVE: It has been suggested that Ca entry through store-operated Ca channels
(SOCs) is regulated by a dynamic interplay between the endoplasmic reticulum Ca
stores and the mitochondria. These relationships drive the activation and
inactivation of SOCs, yet it remains unclear whether this regulation of SOCs by
mitochondria is altered in the aorta of spontaneously hypertensive rats (SHRs).
METHODS: We performed a thorough study of the mitochondrial membrane potential,
the ability of mitochondria to deal with cytosolic Ca, capacitative Ca entry
(CCE), and stromal interaction molecule 1 (STIM1) and calcium release-activated
calcium modulator 1 (orai1) protein expression, as well as the contractile
capacity of aortic rings, in normotensive Wistar Kyoto rats (WKYs) and SHRs.
RESULTS: Changes were observed in aortic tissue and cultured vascular smooth
muscle cells isolated from SHRs relative to WKYs, including more depolarized
mitochondria, stronger CCE upon the addition of Ca, larger cytosolic Ca
transients (cytosolic Ca concentration) or aortic ring contraction elicited by
endoplasmic reticulum depletion and a significant increase in STIM1 protein
expression but not of orai1. CONCLUSION: These results suggest that the impaired
Ca buffering capacity of partially depolarized mitochondria dysregulates CCE,
leading to overfilling of the endoplasmic reticulum Ca store through enhanced
STIM1/orai1 interactions and an increase in aorta contractions in SHRs. Thus,
understanding the implications of the alterations to STIM1/orai1, and their
relationship to mitochondria, may aid drug development and therapeutic strategies
to treat hypertension, as well as its long-term sequelae in poorly controlled
patients.
PMID- 28403043
TI - Plasma galectin-3 concentrations in patients with primary aldosteronism.
AB - BACKGROUND: The incidence of cardiovascular events is higher in patients with
primary aldosteronism than in patients with essential hypertension (EHT), despite
similar blood pressure levels. This suggests detrimental cardiovascular effects
of aldosterone. Amongst others, it has been suggested that galectin-3 (Gal-3) is
a key mediator in aldosterone-induced myocardial fibrosis. OBJECTIVE: We studied
whether patients with primary aldosteronism have higher plasma Gal-3
concentrations than patients with EHT and evaluated its reversibility after
adrenalectomy. METHODS: In a retrospective cohort from our tertiary referral
centre, we measured plasma Gal-3 concentrations in 78 patients with primary
aldosteronism, 39 cured primary aldosteronism patients after adrenalectomy and 56
patients with EHT. Paired samples were available in 11 patients (preadrenalectomy
and postadrenalectomy). We compared plasma Gal-3 levels by univariate analysis of
covariance with correction for cardiovascular risk factors, plasma creatinine
concentration, plasma potassium levels and alcohol intake. RESULTS: Adjusted
plasma Gal-3 concentrations in patients with primary aldosteronism, patients
after adrenalectomy and patients with EHT were 11.39 +/- 0.60, 11.64 +/- 0.81 and
11.41 +/- 0.73 ng/ml, respectively (mean +/- SD; P = 0.95). In 11 patients of
whom paired samples were available, mean Gal-3 concentrations increased from
10.03 +/- 1.67 ng/ml preadrenalectomy to 14.36 +/- 2.07 ng/ml postadrenalectomy
(P < 0.01). CONCLUSION: In patients with primary aldosteronism, plasma Gal-3
concentrations are not elevated when compared with patients with EHT, and levels
do not decrease after adrenalectomy. These results are in contrast to previous
studies and do not support a pathophysiological role of plasma Gal-3 in the
increased cardiovascular risk in patients with primary aldosteronism.
PMID- 28403044
TI - Comparing First- and Second-year Palivizumab Prophylaxis in Patients With
Hemodynamically Significant Congenital Heart Disease in the CARESS Database (2005
2015).
AB - BACKGROUND: Respiratory syncytial virus hospitalization (RSVH) rates in children
<2 years of age with hemodynamically significant congenital heart disease (HSCHD)
are 2- to 4-fold higher compared with healthy term infants. Pediatric
recommendations differ as to whether palivizumab is beneficial beyond 1 year of
age. The objective of this study was to determine whether differences exist in
respiratory-related illness hospitalization (RIH) and RSVH in HSCHD infants
receiving palivizumab during the first year versus second year of life in the
Canadian Registry of Palivizumab. METHODS: The Canadian Registry of Palivizumab
is a prospective database of infants who received >=1 dose of palivizumab in 32
hospitals from 2005 to 2015. Demographic data were collected at enrollment and
RIH events recorded monthly. Infants <24 months of age with HSCHD were recruited.
RESULTS: Of 1909 HSCHD infants, 1380 (72.3%) in the first year (mean age, 4.2
months) and 529 (27.7%) in the second year of life (mean age, 17.8 months)
received prophylaxis. Baseline demographics for day-care attendance, multiple
births, enrollment age and weight differed between the groups (all P < 0.05).
Additionally, second year infants had a more complicated neonatal course, with
significantly longer length of stay (51.2 vs. 24.9 days) compared with those in
the first year. The RIH and RSVH rates in the first year were 11.2% and 2.3% and
in the second year were 10.6% and 1.7%. Cox regression analysis showed similar
hazard for RIH [hazard ratio, 1.9; 95% confidence interval: 0.7-4.6; P = 0.18]
and RSVH [hazard ratio, 2.0; 95% confidence interval: 0.2-16.5; P = 0.52].
CONCLUSIONS: Infants in the first and second year of life had a similar RSVH
hazard. These findings suggest that infants in the second year with HSCHD, who
remain unstable, are equally at risk for RSVH and merit prophylaxis.
PMID- 28403045
TI - Polymorphisms of Mannose-binding Lectin and Toll-like Receptors 2, 3, 4, 7 and 8
and the Risk of Respiratory Infections and Acute Otitis Media in Children.
AB - BACKGROUND: Mannose-binding lectin (MBL) and toll-like receptors (TLRs) are
important components of the innate immune system. We assessed the susceptibility
of children with genetic variants in these factors to respiratory infections,
rhinovirus infections and acute otitis media. METHODS: In a prospective cohort
study, blood samples from 381 Finnish children were analyzed for polymorphisms in
MBL2 at codons 52, 54 and 57, TLR2 Arg753Gln, TLR3 Leu412Phe, TLR4 Asp299Gly,
TLR7 Gln11Leu and TLR8 Leu651Leu. Children were followed up for respiratory
infections until 24 months of age with daily diaries. Polymerase chain reaction
and antigen tests were used for detection of respiratory viruses from nasal
swabs. RESULTS: Children with MBL variant genotype had a mean of 59 days with
symptoms of respiratory infection per year, compared with 49 days in those with
wild-type (P = 0.01). TLR8 polymorphisms were associated with an increased risk
and TLR7 polymorphisms with a decreased risk of recurrent rhinovirus infections
(P = 0.02 for both). TLR2 polymorphisms were associated with recurrent acute
otitis media (P = 0.02). MBL polymorphisms were associated with an increased and
TLR7 polymorphisms with a decreased risk of rhinovirus-associated acute otitis
media (P = 0.03 and P = 0.006, respectively). CONCLUSIONS: Genetic polymorphisms
in MBL and TLRs promote susceptibility to or protection against respiratory
infections. In addition to environmental factors, genetic variations may explain
why some children are more prone to respiratory infections.
PMID- 28403046
TI - Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving
the German Surveillance Unit for Rare Diseases in Childhood.
AB - BACKGROUND: Although bacterial osteomyelitis (BO) is a commonly recognized
diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial
osteitis (NBO). The goal of our study was to distinguish between the 2 disease
entities and better define NBO. METHODS: Using the German Surveillance Unit for
Rare Diseases in Childhood (Erhebungseinheit fur Seltene Paediatrische
Erkrankungen in Deutschland), this prospective study during a 5-year period
captured 657 patients at first diagnosis of either BO (n = 378) or NBO (n = 279)
while analyzing epidemiologic, clinical and radiologic data. RESULTS: BO was
reported in 1.2 per 100,000 children with a higher prevalence in younger male
patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients
tended to present with fevers (68%), elevated inflammation markers (82%) and
local swelling (62%) but a shorter course of symptoms than NBO patients. NBO
patients presented in good general health (86%) and were more likely to have
multifocal lesions (66%). Staphylococcus aureus was the most prominent pathogen
(83%), with only one methicillin-resistant S. aureus reported. Complications
ranged from arthritis adjacent to the lesion to hyperostosis and vertebral
fractures. CONCLUSIONS: BO and NBO can be distinguished based on symptoms,
associated diseases and inflammation markers. NBO should always be considered in
pediatric patients presenting with bone lesions and pain, especially in young
female patients presenting with good general health, minimal inflammation markers
and multifocal lesions in the vertebrae, clavicle and sternum.
PMID- 28403047
TI - Risk Factors in Children Older Than 5 Years With Pneumococcal Meningitis: Data
From a National Network.
AB - BACKGROUND: The occurrence of meningitis in children >5 years old may be
associated with specific predisposing factors that can be anatomic, such as
cerebrospinal fluid fistula or breach, or related to genetic susceptibility or N
inborn or acquired immunologic defect. This study aimed to assess the anatomical
and immunologic risk factors in children >5 years old with pneumococcal
meningitis and prospectively enrolled in the French national meningitis network.
METHODS: We analyzed all data for children who were 5-15 years old with a
diagnosis of pneumococcal meningitis between 2001 and 2013. We describe the
frequency and typology of the anatomic or immunologic risk factors, the clinical
features and the pneumococcal serotypes. RESULTS: Among the 316 patients with
pneumococcal meningitis, the mortality rate was 9.5% and 23.1% of cases presented
complications (abscess, coma, hemodynamic failure, thrombophlebitis cerebral or
deafness). In total, 108 children (34%) showed risk factors, the most frequent
being anatomic: 70 cases (22.8%) were related to a cerebrospinal fluid breach or
fistula and 55 (17.9%) to immunodeficiency, primary or acquired. Serotype data
were available for 207 pneumococcal isolates (65.5%). The most frequent serotypes
were as follows: 3, 18C, 19A and 19F between 2001 and 2009 and 19F, 3, 19A, 12F,
22F, 17F and 24F after 2009. CONCLUSIONS: We describe the largest cohort of
children >5 years old with pneumococcal meningitis. One third of the children had
risk factors justifying a complete immunologic and radiologic work-up.
PMID- 28403048
TI - Prevalence of Mycoplasma pneumoniae Infection in Malagasy Children.
AB - BACKGROUND: Childhood community-acquired pneumonia is a leading cause of
childhood morbidity in low-income countries. The etiologic agents are usually
Staphylococcus aureus, Streptococcus pneumoniae and Mycoplasma pneumoniae. M.
pneumoniae was recognized as a cofactor in asthmatic disease. High asthma
prevalence was reported in Madagascar. Our aim was to clarify the prevalence of
M. pneumoniae infection in this country and its relationship with asthma.
METHODS: A prospective study was conducted in 351 children (from 2 to 16 years of
age) from January 2012 to December 2014. According to the clinical symptoms,
children were enrolled in 3 groups: "control group" (CG, n = 106), "asthma group"
(n = 129) and "pneumonia group" (n = 116). The IgG and IgM M. pneumoniae status
was evaluated by an enzyme-linked immunosorbent assay. Clinical signs of
infection, socioeconomic data and antimicrobial treatment were recorded. RESULTS:
The overall prevalence of M. pneumoniae infection was 18.2%. The multivariate
analysis demonstrated that M. pneumoniae infection was significantly more
frequent in the CG [pneumonia group vs. CG: odds ratio = 0.45 (0.21-0.91), P =
0.037 and asthma group vs. CG: odds ratio = 0.39 (0.18-0.87), P = 0.021]. The C
reactive protein value was significantly higher in children with M. pneumonia
positive serology (85 vs. 61 mg/L, P = 0.03). Of note, 99 (41%) children received
antibiotics before attending. CONCLUSIONS: We report a prevalence of 18.2% for M.
pneumoniae infection in children in Madagascar. The prevalence of M. pneumoniae
infection was higher in the control patients than in asthmatic ones.
PMID- 28403049
TI - Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low
Birth Weight Infants: Opportunities for Antibiotic Stewardship.
AB - BACKGROUND: Most very low birth weight (VLBW, birth weight <1500 g) infants
receive empiric antibiotics for risk of early-onset sepsis (EOS). The objective
of this study was to determine the characteristics of VLBW infants with culture
confirmed EOS at a single center during 25 years and to identify opportunities
for antibiotic stewardship. METHODS: Retrospective cohort study includes VLBW
infants admitted from 1990 to 2015. EOS was defined as isolation of a pathogen in
blood or cerebrospinal fluid culture obtained at <72 hours of age. Clinical and
microbiologic characteristics of EOS case infants were obtained by review of
medical, laboratory and administrative records. Blood culture, antibiotic
initiation and maternal discharge code data were available for all VLBW infants
born between 1999 and 2013. RESULT: One-hundred nine EOS cases (20.5/1000 VLBW
births) occurred during the study period. Preterm labor, preterm rupture of
membranes and/or the obstetrical diagnosis of chorioamnionitis were present in
106/109 cases (97%). Obligate anaerobic organisms accounted for 16% of cases.
Time to culture positivity was 36 hours for 88% and 48 hours for 98% of cases.
From 1999 to 2013, 97% of VLBW infants were evaluated for EOS and 90%
administered empiric antibiotics; 22% of these infants were born by cesarean
section to mothers with preeclampsia and without preterm labor or
chorioamnionitis and had a 12-fold lower incidence of EOS compared with the
remaining infants. CONCLUSION: Decisions to initiate and discontinue empiric
antibiotics among VLBW infants can be informed by the delivery characteristics of
infected infants and by local microbiologic data.
PMID- 28403050
TI - Ceftaroline Activity Tested Against Bacterial Isolates Causing Community-acquired
Respiratory Tract Infections and Skin and Skin Structure Infections in Pediatric
Patients From United States Hospitals: 2012-2014.
AB - Ceftaroline fosamil has recently received US Food and Drug Administration
approval for treatment of acute bacterial skin/skin structure infections (SSSIs),
including those caused by methicillin-resistant Staphylococcus aureus and
community-acquired bacterial pneumonia for pediatric patients >=2 months old. We
evaluated the potency and spectrum of ceftaroline and comparators when tested
against community-acquired respiratory tract infection (CARTI) and SSSI pathogens
from pediatric patients. A total of 3141 consecutive, unique pediatric patient
isolates of clinical significance (1460 CARTI and 1681 SSSI isolates) were
collected from 29 US medical centers and tested for susceptibility to ceftaroline
and comparators by broth microdilution methods. The organism collection included
Streptococcus pneumoniae (n = 754), Haemophilus influenzae (487), S. aureus
(1399), beta-hemolytic streptococci (214), Enterobacteriaceae (112), Pseudomonas
aeruginosa (58), Klebsiella spp. (39), Escherichia coli (26) and miscellaneous
other bacteria (52). Susceptibility results were analyzed according to patient
age as follows: <=1, 2-5, 6-12 and 13-17 years old. Overall, 99%-100% of Gram
positive isolates and H. influenzae were susceptible to ceftaroline according to
Clinical and Laboratory Standards Institute clinical breakpoint criteria.
Ceftaroline exhibited potent in vitro activity against bacterial pathogens from
CARTI and SSSI recently (2012-2014) collected from pediatric patients in US
medical centers. Ceftaroline was particularly active against methicillin
resistant S. aureus from SSSI ([minimum inhibitory concentration for 50% and 90%
of isolates (MIC50/90,)] and ceftriaxone-nonsusceptible isolates of S. pneumoniae
from CARTI (MIC50/90, 0.25/0.5 MUg/mL; 98.3% susceptible).
PMID- 28403052
TI - Second- and Third-line Antiretroviral Therapy for Children and Adolescents: A
Scoping Review.
AB - BACKGROUND: The World Health Organization identified a need for evidence to
inform revision of second- and third-line antiretroviral therapy (ART) options in
children failing ART. We performed an in-depth scoping review of all available
literature on second-line and subsequent ART regimens in children younger than 18
years. METHODS: We comprehensively searched, without language or date
limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE,
the World Health Organization's International Clinical Trials Registry Platform
and ClinicalTrials.gov. RESULTS: The search retrieved 1982 records. Eighteen
studies provided efficacy data: 1 randomized controlled trial, 7 phase II trials,
5 prospective and 5 retrospective cohorts. Five studies evaluated regimens in
children failing first-line ART, 4 in children with multidrug resistance and 9 in
children with variable treatment experience. Only 10/18 studies reported week 48
or month 12 outcomes. The overall proportion of children with virologic
suppression defined by study at week 48 was 61.8%. Although the randomized
controlled trial had low risk of bias, outcomes were similar between groups
because of highly active optimized background regimens. All phase II and
prospective studies were judged to have moderate to high risk of bias. No study
compared currently recommended lopinavir-based second-line regimens for
nonnucleoside reverse transcriptase inhibitor failures to other non-nonnucleoside
reverse transcriptase inhibitor regimens head-to-head. CONCLUSIONS: We found no
evidence comparing current World Health Organization-recommended second- and
third-line ART regimens with regimens including drugs of interest: raltegravir,
darunavir, etravirine and atazanavir. Randomized controlled trials or prospective
cohort studies with comparator arms, and bridging studies, ideally conducted in
resource-limited settings, are required to guide future recommendations.
PMID- 28403051
TI - Modelling CD4 T Cell Recovery in Hepatitis C and HIV Co-infected Children
Receiving Antiretroviral Therapy.
AB - BACKGROUND: The effect of hepatitis C virus (HCV) coinfection on CD4 T cell
recovery in treated HIV-infected children is poorly understood. OBJECTIVE: To
compare CD4 T cell recovery in HIV/HCV coinfected children with recovery in HIV
monoinfected children. METHOD: We studied 355 HIV monoinfected and 46 HIV/HCV
coinfected children receiving antiretroviral therapy (ART) during a median follow
up period of 4.2 years (interquartile range: 2.7-5.3 years). Our dataset came
from the Ukraine pediatric HIV Cohort and the HIV/HCV coinfection study within
the European Pregnancy and Paediatric HIV Cohort Collaboration. We fitted an
asymptotic nonlinear mixed-effects model of CD4 T cell reconstitution to age
standardized CD4 counts in all 401 children and investigated factors predicting
the speed and extent of recovery. RESULTS: We found no significant impact of HCV
coinfection on either pre-ART or long-term age-adjusted CD4 counts (z scores).
However, the rate of increase in CD4 z score was slower in HIV/HCV coinfected
children when compared with their monoinfected counterparts (P < 0.001). Both
monoinfected and coinfected children starting ART at younger ages had higher pre
ART (P < 0.001) and long-term (P < 0.001) CD4 z scores than those who started
when they were older. CONCLUSIONS: HIV/HCV coinfected children receiving ART had
slower CD4 T cell recovery than HIV monoinfected children. HIV/HCV coinfection
had no impact on pre-ART or long-term CD4 z scores. Early treatment of HIV/HCV
coinfected children with ART should be encouraged.
PMID- 28403053
TI - Zika Virus Infection Associated With Congenital Birth Defects in a HIV-infected
Pregnant Woman.
AB - We describe a case of Zika virus infection acquired during the first trimester in
a HIV-infected pregnant woman that led to multiple fetal malformations and fetal
demise in Rio de Janeiro, Brazil.
PMID- 28403054
TI - Prevalence of Cryptosporidium Carriage and Disease in Children With Primary
Immune Deficiencies Undergoing Hematopoietic Stem Cell Transplant in Northern
Europe.
AB - A prospective cohort study of children with primary immunodeficiencies undergoing
hematopoietic stem cell transplant in the United Kingdom investigated the extent
and significance of Cryptosporidium carriage in this high risk group. Three of 42
children recruited were infected with Cryptosporidium, a lower proportion than
previously described. One had serious disease. The underlying immunodeficiency
likely had a bearing on the clinical presentation and possible outcome of
infection.
PMID- 28403055
TI - Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus
influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With
Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open,
Controlled Study.
AB - BACKGROUND: Immunogenicity, safety and reactogenicity of the 10-valent
pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD
CV) were evaluated in children with sickle cell disease (SCD), who are at
increased risk for infections. METHODS: In this phase III, open-label, single
center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or
without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age
(<6 months; <6S and <6NS groups) received 3 primary doses and a booster dose of
PHiD-CV coadministered with routine childhood vaccines; children 7-11 months of
age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD
CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up
doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F
inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic
activity. Responses to other antigens were measured by enzyme-linked
immunosorbent assay. Adverse events were recorded. RESULTS: One month postprimary
vaccination, for each vaccine serotype >=98% of infants in the <6S and <6NS
groups had antibody concentrations >=0.2 ug/mL, except for 6B (>=85%) and 23F
(>=89%). Immune responses to PHiD-CV after age-appropriate vaccination in
children <2 years did not appear influenced by SCD. All infants were
seroprotected/seropositive for diphtheria, tetanus and Bordetella pertussis
antigens postprimary and booster vaccination. Safety and reactogenicity profiles
were similar in children with or without SCD. CONCLUSIONS: PHiD-CV was
immunogenic with an acceptable safety profile in children with and without SCD
starting vaccination at 8 weeks to 23 months of age.
PMID- 28403056
TI - Risk of Pertussis in Relation to Degree of Prematurity in Children Less Than 2
Years of Age.
AB - BACKGROUND: A few previous studies reported increased risk of pertussis in
children with birth weight less than 2500 g. The risk of pertussis by degree of
prematurity has not been determined in a cohort study. The vaccine effectiveness
(VE) against reported pertussis in preterm infants is unknown. METHODS: Data were
obtained from the Medical Birth Registry of Norway (1998-2010) and linked to
other national registries. In total, 713,166 children were included in our study
and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence
intervals (CIs) were estimated with Poisson regression. RESULTS: We identified
999 reported cases of pertussis. We observed a higher rate of reported pertussis
in preterm than in full-term infants, IRR = 1.65 (95% CI: 1.32-2.07). Compared to
full-term infants, the risk of reported pertussis in infants born at gestational
age (GA) 35-36, 32-34 and 23-27 weeks were higher [IRRs = 1.49 (95% CI: 1.11
2.01), 1.63 (95% CI: 1.06-2.51) and 4.49 (95% CI: 2.33-8.67), respectively].
Moreover, preterm infants had a higher rate of pertussis-related hospitalization
than full-term infants [IRR = 1.99 (95% CI: 1.47-2.71)]. The VE against reported
pertussis for the third dose was 88.8% (95% CI: 84.3-92.0) in full-term infants
and 93.0% (95% CI: 85.8-96.5) in preterm infants. CONCLUSIONS: In this cohort
study, preterm infants including those born at GA 35 and 36 weeks had increased
risk of reported pertussis. The VE was similar in preterm and full-term infants.
PMID- 28403057
TI - Fever in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Pediatric
Cases: Laboratory Work-up and Antibiotic Therapy.
AB - Fever is a symptom that often accompanies skin eruptions, especially in children.
It can be a sign of an infectious condition presenting with exanthems or it may
precede an exanthematous eruption. Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) are severe reactions affecting skin and mucosa with
blisters and erosions. High fever occurs in these conditions, frequently before
the skin and/or mucosa is affected.
PMID- 28403058
TI - Multiorgan Involvement Confounding the Diagnosis of Bartonella henselae Infective
Endocarditis in Children With Congenital Heart Disease.
AB - Two children with congenital heart disease status post surgical correction
presented with prolonged constitutional symptoms, hepatosplenomegaly and
pancytopenia. Concern for malignancy prompted bone marrow biopsies that were
without evidence thereof. In case 1, echocardiography identified a multilobulated
vegetation on the conduit valve. In case 2, transthoracic, transesophageal and
intracardiac echocardiography were performed and were without evidence of cardiac
vegetations; however, pulmonic emboli raised concern for infective endocarditis.
Both patients underwent surgical resection of the infected material and had
histopathologic evidence of infective endocarditis. Further diagnostics
identified elevated cytoplasmic antineutrophil cytoplasmic antibodies and
antiproteinase 3 antibodies in addition to acute kidney injury with crescentic
glomerulonephritis on renal biopsy. Serologic evidence of infection with
Bartonella henselae was observed in both patients. These 2 cases highlight the
potential multiorgan involvement that may confound the diagnosis of culture
negative infective endocarditis caused by B. henselae.
PMID- 28403059
TI - Mycobacterium gordonae Skin Infection in an Immunocompetent Child.
AB - Mycobacterium gordonae is a slow growing, pigmented, nontuberculous
mycobacterium. It is commonly associated with environmental contamination of
clinical specimens, but it is also a recognized pathogen in immunocompromised
hosts. We describe an immunocompetent child with a spontaneously occurring skin
ulcer on the face caused by M. gordonae infection.
PMID- 28403060
TI - The Risk of Mycobacterium tuberculosis Transmission from Pediatric Index Cases to
School Pupils.
AB - This study is the largest report on Mycobacterium tuberculosis transmission rate
(TR) from children with pulmonary tuberculosis to school pupils. Higher TR
(around 21.6%) was observed in contacts of smear-positive children. TR from
pediatric smear-negative index cases was around 0. If our data are confirmed,
school contacts of a smear-negative index case could be screened only by clinical
evaluation and tuberculin skin test, avoiding the routine use of chest
radiographs in children less than 5 years of age as well.
PMID- 28403061
TI - Microcephaly Case Fatality Rate Associated with Zika Virus Infection in Brazil:
Current Estimates.
AB - Considering the currently confirmed cases of microcephaly and related deaths
associated with Zika virus in Brazil, the estimated case fatality rate is 8.3%
(95% confidence interval: 7.2-9.6). However, a third of the reported cases remain
under investigation. If the confirmation rates of cases and deaths are the same
in the future, the estimated case fatality rate will be as high as 10.5% (95%
confidence interval: 9.5-11.7).
PMID- 28403062
TI - Twelve-year-old With Chronic Chest and Abdominal Pain.
PMID- 28403063
TI - Leishmaniasis Recidivans in Pediatric Patients.
PMID- 28403065
TI - Denouement.
PMID- 28403064
TI - Perinatally Acquired Chikungunya Infection: Reports From the Western Hemisphere.
PMID- 28403068
TI - Malignant Melanoma in African-Americans: A Population-Based Clinical Outcomes
Study Involving 1106 African-American Patients from the Surveillance,
Epidemiology, and End Result (SEER) Database (1988-2011).
AB - Malignant melanoma accounts for 75% of all skin cancer deaths and is potentially
curable if identified early. Although melanoma is rare in African-Americans (AA),
it is associated with a worse prognosis than in Caucasians. This study examines
the demographic, pathologic, and clinical factors impacting AA melanoma
outcomes.Data for 1106 AA and 212,721 Caucasian cutaneous melanoma patients were
abstracted from the Surveillance, Epidemiology, and End Result (SEER) database
(1988-2011). Data were grouped on the basis of histological subtypes:
"Superficial Spreading" (SS), "Nodular" (NM), "Lentigo Maligna" (LM), "Acral
Lentiginous" (AL), and "Not otherwise specified" (NOS).Cutaneous malignant
melanoma occurs most commonly in the sixth and seventh decade of life. Caucasian
patients presented most commonly with trunk melanomas (34.5%), while lower
extremity melanomas were more common in AAs (56.1%), P < 0.001. AAs presented
with deeper tumors, more advanced stage of disease, and higher rates of
ulceration and lymph node positivity than Caucasians. Cancer-specific mortality
was significantly higher, while 5-year cancer-specific survival was significantly
lower among AAs for NM and AL subtypes. Multivariate analysis identified male
gender, regional and distant stage, NM and AL subtypes as independently
associated with increased mortality among both ethnic groups.AAs present most
often with AL melanoma on the lower extremities, and with deeper and more
advanced stage lesions. AAs have higher cancer-specific mortality for NM and LM
than Caucasians. Melanoma education for AA patients and health care providers is
needed to increase disease awareness, facilitate early detection, and promote
access to effective treatment.
PMID- 28403069
TI - Using a pedicle pectoralis major musculocutaneous flap in head and neck
reconstruction after modified radical mastectomy: A case report.
AB - RATIONALE: A pedicle pectoralis major musculocutaneous (PMMC) flap is one of the
strategies for head and neck reconstruction. Seldom studies reported the case in
which the skin area of previous modified radical mastectomy (MRM) had been used
as a PMMC flap in head and neck reconstruction. PATIENT CONCERNS: An 84-year-old
female who had suffered from left breast cancer and undergone a left modified
radical mastectomy (MRM) more than 20 years earlier. DIAGNOSES: She had squamous
cell carcinoma of the tongue and had undergone partial glossection and left
modified radial neck dissection. Four months later, a left submandibular mass was
noted with progressive enlargement and the biopsy revealed recurrent carcinoma.
INTERVENTIONS: Left marginal mandibulectomy with radical neck dissection was
performed and the neck area was reconstructed by a left pedicle PMMC flap
harvested from the left chest wall which had the previous MRM scar. OUTCOMES: The
post-operative course was uneventful with complete survival of the flap. The
patient received post-operative adjuvant radiotherapy at the left neck and no
delayed wound disruption or flap necrosis was noted six months after surgery.
LESSONS: A pedicle PMMC flap may be harvested to achieve a functionally as well
as an aesthetically pleasing outcome without compromising its viability despite
the previous MRM.
PMID- 28403070
TI - Genetic association of aromatic hydrocarbon receptor and its repressor gene
polymorphisms with risk of rheumatoid arthritis in Han Chinese populations.
AB - The goal of this study was to evaluate the potential relationship among
polymorphisms of aromatic hydrocarbon receptor, aromatic hydrocarbon receptor
repressor, and rheumatoid arthritis (RA) susceptibility as well as the
association among the polymorphisms of aromatic hydrocarbon receptor, aromatic
hydrocarbon receptor repressor, and their expression.We performed a hospital
based, case-control study of 400 patients with RA and 726 healthy controls in Han
Chinese populations. Two single-nucleotide polymorphisms were selected for
genotyping including aromatic hydrocarbon receptor (rs2066853) and aromatic
hydrocarbon receptor repressor (rs2292596).To single-nucleotide polymorphism
rs2292596, a statistically significantly increased risk of RA was found to be
associated with the G allele of rs2292596; the odds ratio was 2.170 (95%
confidence interval: 1.820-2.587). Unfortunately, no significant differences
exhibited in the allelic and the genotype frequencies of rs2066853 between 2
groups. We failed to find any association between rs2066853, rs2292596 genotypes
and their expression of patients, respectively. No statistical relationship was
found between aromatic hydrocarbon receptor, aromatic hydrocarbon receptor
repressor at messenger Ribonucleic acid levels and clinical data, either.This
study demonstrated that the polymorphisms of rs2292596 was significant with
genetic susceptibility to RA patients; furthermore, it suggests the G allele of
rs2292596 might be associated with a dangerous effect on RA in Han Chinese
populations.
PMID- 28403071
TI - The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with
diffuse large B-cell lymphoma.
AB - Latest study showed that a novel translocation between programmed cell death
ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can
be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct
overexpression in tumor cells at RNA level. However, the expressed pattern of
these 2 genes at protein level in DLBCL remains largely unknown, and the clinical
relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues
from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD
1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1,
and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves
with log rank test, and Cox's proportional hazards regression model.PD-1 was
mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD
L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in
nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly
associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL
with PD-L1 or TP63 expression in tumor cells showed low International Prognostic
Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged
overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression
was associated with worse clinical outcome of patients (P = 0.049).
Immunoreactivity of TP63 was not correlated with patients' survival time.
Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were
significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic
significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD
L1/TP63 blockade may be a potential therapeutic strategy for some patients.
PMID- 28403073
TI - Quantitative Analysis of Immunohistochemistry in Melanoma Tumors.
AB - Identification of positive staining is often qualitative and subjective. This is
particularly troublesome in pigmented melanoma lesions, because melanin is
difficult to distinguish from the brown stain resulting from immunohistochemistry
(IHC) using horse radish peroxidase developed with 3,3'-Diaminobenzidine (HRP
DAB). We sought to identify and quantify positive staining, particularly in
melanoma lesions. We visualized G-protein coupled estrogen receptor (GPER)
expression developed with HRP-DAB and counterstained with Azure B (stains
melanin) in melanoma tissue sections (n = 3). Matched sections (n = 3), along
with 22 unmatched sections, were stained only with Azure B as a control. Breast
tissue (n = 1) was used as a positive HRP-DAB control. Images of the stained
tissues were generated using a Nuance Spectral Imaging Camera. Analysis of the
images was performed using the Nuance Spectral Imaging software and SlideBook.
Data was analyzed using a Kruskal-Wallis one way analysis of variance (ANOVA). We
showed that a pigmented melanoma tissue doubly stained with anti-GPER HRP-DAB and
Azure B can be unmixed using spectra derived from a matched, Azure B-only
section, and an anti-GPER HRP-DAB control. We unmixed each of the melanoma
lesions using each of the Azure B spectra, evaluated the mean intensity of
positive staining, and examined the distribution of the mean intensities (P =
.73; Kruskal-Wallis). These results suggest that this method does not require a
matched Azure B-only stained control tissue for every melanoma lesion, allowing
precious tissues to be conserved for other studies. Importantly, this
quantification method reduces the subjectivity of protein expression analysis,
and provides a valuable tool for accurate evaluation, particularly for pigmented
tissues.
PMID- 28403072
TI - Retinal microvascular alterations related to diabetes assessed by optical
coherence tomography angiography: A cross-sectional analysis.
AB - Fluorescein angiography has been so far the gold-standard test to assess diabetic
macular ischemia (DMI), a cause of irreversible visual impairment in diabetic
patients. The aim of this study was to investigate foveal avascular zone (FAZ)
and perifoveal microcirculation changes in eyes with nonproliferative diabetic
retinopathy (NPDR) using optical coherence tomography angiography (OCTA), a new
and noninvasive vascular imaging technique.Cross-sectional study including eyes
of diabetic patients with NPDR.All patients underwent medical history, best
corrected visual acuity (BCVA) measurement, slit-lamp and fundus examination,
multicolor imaging, SD-OCT, and swept-source OCT. OCTA was performed in order to
assess macular superficial and deep capillary plexus, and swept-source OCT was
performed to evaluate the central choroidal thickness.Fifty-eight eyes of 35
patients with a mean age of 61.8 years (+/-12.1) with mean HbA1C level of 7.6%
(+/-1.5) were included in this study. Among them, 19 eyes had mild NPDR, 24 eyes
had moderate NPDR, and 15 eyes had severe NPDR. There was a significant
progression between NPDR stages for FAZ grade (P < 0.0001), surface (P = 0.0036)
and perimeter (P = 0.0001), and for superficial capillary plexus nonperfusion
index (NPI) (P = 0.0009). Moreover, a significant correlation was found between
NPI and BCVA (P = 0.007).OCT angiography is a useful noninvasive tool to explore
early phases of diabetic retinopathy, which are not routinely explore with
fluorescein angiography and not precisely enough with color photographs. NPI and
foveal avascular zone parameters are correlated with glycated hemoglobin in
patients with NPDR. If confirmed by further studies, these results could
represent a mean to sensibilize diabetic patients to their disease.
PMID- 28403074
TI - Anxiety level and correlates in methamphetamine-dependent patients during acute
withdrawal.
AB - Anxiety is often a core element of withdrawal symptoms; however, risk factors
associated with anxiety symptoms during the early stage of withdrawal in
methamphetamine (METH) users are not well understood. Two hundred ten METH
dependent subjects who had been abstinent for 1 to 7 days were recruited. We used
a set of self-administrative questionnaires eliciting information on
sociodemographics, detailed drug use history and anxiety. Beck Anxiety Inventory
(BAI) was used to measure anxiety symptoms. METH users had a mean BAI score of
6.9; 72 (34.3%) of the study sample had anxiety symptoms during acute METH
withdrawal, including 42 (20.0%) with mild anxiety, 25 (11.9%) with moderate
anxiety, and 5 (2.4%) with severe anxiety. In addition, gender (female), higher
frequency of drug use, and history of polysubstance use were significantly
correlated with anxiety symptoms during acute METH withdrawal. Anxiety symptoms
appear to be common during the first week of METH abstinence, and several risk
factors are identified.
PMID- 28403075
TI - Gabapentin can decrease acute pain and morphine consumption in spinal surgery
patients: A meta-analysis of randomized controlled trials.
AB - BACKGROUND: Approximately 80% of patients who underwent spinal surgeries
experience moderate to extreme postoperative pain. Gabapentin was used as an
adjunct for the management of acute pain in approximately half of enhanced
recovery programs. This meta-analysis aimed to illustrate the efficacy and safety
of gabapentin for pain management following spinal surgery. METHODS: In January
2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of
Science, Cochrane Database of Systematic Reviews, and Google database. Data on
patients prepared for spine surgery in studies that compared gabapentin versus
placebo were retrieved. The primary endpoint was the visual analog scale (VAS) at
12 hours and 24 hours and total morphine consumption. The secondary outcomes were
complications that included nausea, dizziness, somnolence, headache, pruritus,
urine retention, and vomiting. After testing for publication bias and
heterogeneity between studies, data were aggregated for random-effects models
when necessary. RESULTS: Seven clinical studies with 581 patients (gabapentin
group=383, control group=198) were ultimately included in the meta-analysis.
Gabapentin was associated with reduced pain scores at 12 hours and 24 hours,
corresponding to a reduction of 11.18 points (95% CI, -13.85 to -8.52 points) at
12 hours and 9.94 points (95% CI, -13.99 to -5.89 points) at 24 hours on a 100
point VAS. Similarly, gabapentin was associated with a reduction in total
morphine consumption (-2.04, 95% CI -2.71, -1.37). Furthermore, gabapentin can
reduce the occurrence of vomiting (risk ratio [RR] 0.46, 95% CI 0.27, 0.78, P =
0.004), urine retention (RR = 0.57, 95% CI 0.34, 0.98, P = 0.041, NNT = 11.9) and
pruritus (RR = 0.38, 95% CI 0.22, 0.66, P = 0.001, NNT = 5.6) and the number
needed to treat (NNT = 20.1). There were no significant differences in the
occurrence of nausea, dizziness, somnolence, or headache. CONCLUSIONS: Gabapentin
was efficacious in the reduction of postoperative pain, total morphine
consumption, and morphine-related complications following spine surgery. In
addition, a high dose (>=900 mg/d) of gabapentin is more effective than a low
dose (<900 mg/d). The number of included studies is limited, and more studies are
needed to verify the effects of gabapentin in spinal surgery patients.
PMID- 28403076
TI - Diffuse melanosis cutis related to dermal micrometastases as the first clinical
symptom of distant metastatic malignant melanoma: Case report.
AB - RATIONALE: Diffuse melanosis cutis (DMC) is a very rare sign of malignant
melanoma progression. The condition usually develops after approximately one year
from melanoma diagnosis in a patient with metastatic tumors and after anticancer
treatment with cytostatic medications. PATIENT CONCERNS: A 72-year old Caucasian
man was admitted to the Department of Dermatology with DMC for 4 months and the
history of two melanomas treated surgically 30 years and 9 months before present
hospitalization. DIAGNOSIS: Histological and immunohistochemical examinations of
DMC biopsy indicated melanoma metastatic cells as well as free deposits of
melanin and melanophage presence in the dermis. INTERVENTIONS: The patient
refused to the treatment. OUTCOMES: The patient died eight months after DMC
appeared. LESSONS: DMC is a rare presentation of advanced MM and is a bad
prognostic factor. The pathomechanisms of the discoloration of the skin are not
fully explained. The role of micrometastases, as well as melanin precursors,
released during lysis of MM metastases, and growth factors may play a role in the
development of the symptom.
PMID- 28403077
TI - High expression of CD8 predicts favorable prognosis in patients with lung
adenocarcinoma: A cohort study.
AB - Lung carcinoma is the most common cause of malignant death worldwide. CD8 T
cells, as critical elements in antitumor immunity, could function as good
prognostic indicators in various kinds of cancers such as renal cell carcinoma
and colorectal cancer, but its prognostic role in lung adenocarcinoma is still
unclear. The objective of this study was to explore the prognostic role of CD8
expression in lung adenocarcinoma.Paired tumor and adjacent noncancerous tissues
were obtained from 102 patients with lung adenocarcinoma, and CD8 expression of
these samples was examined by immunohistochemistry. We evaluated the
relationships between the expression of CD8 and pathological grade, TNM stage,
clinical stage, as well as overall survival (OS).Expression of CD8 was
significantly increased in lung adenocarcinoma compared with that in adjacent
lung adenocarcinoma (P < .001). CD8 expression was negatively correlated with
pathological grade (r = -0.216, P = .022) and N stage (r = -0.372, P < .001),
while no statistical correlation with T stage, or clinical stage. Importantly, OS
was numerically increased in patients with high expression of CD8 than the group
of intermediate and low CD8 expression (P = .12). Furthermore, CD8 could
significantly increase OS (P = .043, HR: .713, 95%CI: .515-.989) by univariate
Cox's proportional hazards regression analysis.Our data indicated that expression
of CD8, as a protective factor, is correlated with the outcome of patients with
lung adenocarcinoma. Furthermore, CD8 might be a novel prognostic biological
marker for patients with lung adenocarcinoma.
PMID- 28403078
TI - Renal dysplasia characterized by prominent cartilaginous metaplasia lesions in
VACTERL association: A case report.
AB - BACKGROUND: Renal dysplasia is the most important cause of end-stage renal
disease in children. The histopathological characteristic of dysplasia is
primitive tubules with fibromuscular disorganization. Renal dysplasia often
includes metaplastic cartilage. Metaplastic cartilage in renal dysplasia has been
explained as occurring secondary to vesicoureteral reflux (VUR). Additionally,
renal dysplasia is observed in renal dysplasia-associated syndromes, which are
combinations of multiple developmental malformations and include VACTERL
association. CASE PRESENTATION: We observed the following multiple developmental
malformations in a 108-day-old male infant during a nephrectomy: a nonfunctioning
right kidney with VUR, hemidiaphragmatic eventration, a ventricular septal defect
(VSD) with tetralogy of Fallot in the heart, cryptorchidism, and hyperdactylia.
These developmental anomalies satisfied the diagnostic criteria for VACTERL
association. A surgical specimen of the right nonfunctioning kidney revealed
prominent cartilaginous metaplasia in the renal dysplasia with VUR. The densities
of the ectopic cartilaginous lesions in this nonfunctioning kidney were
extraordinarily high compared with other renal dysplasia cases. Giemsa banding of
his genome produced normal results. The patient has not undergone further
detailed genomic investigation. CONCLUSION: This case might be a novel type of
VACTERL association, that is, renal dysplasia combined with prominent
cartilaginous metaplasia, tetralogy of Fallot and VSD of the heart,
hemidiaphragmatic eventration, and hyperdactylia.
PMID- 28403079
TI - Toward a mediation model for nurses' well-being and psychological distress
effects of quality of leadership and social support at work.
AB - Given the lack of active nurses in industrialized countries throughout the world,
in combination with demographic changes, it is of utmost importance to protect
nurses' well-being and to prevent psychological distress, because of their strong
association with premature occupational leave. The aim of this study was to
investigate the effects of quality of leadership and social support at work on
well-being and psychological distress of nurses and to determine whether nurses'
overcommitment mediates the relationship between the abovementioned determinants
and the outcomes. A cross-sectional survey design was used to gather our data.
This study utilized part of the database of the Nurses' Early Exit Study. A total
of 34,771 nurses (covering all nurse qualifications) working in hospitals,
nursing homes, and home-care institutions in 8 European countries filled out a
questionnaire (response rate = 51.4%). For all model variables (job satisfaction,
satisfaction with salary, positive affectivity, personal burnout, negative
affectivity, quality of leadership, social support from immediate supervisor,
social support from near colleagues, and overcommitment), psychometrically sound,
that is, valid and reliable measures were used. Outcomes from testing a
structural equation mediation model indicated that, respectively, positive and
negative influences of leadership quality and social support from supervisor and
colleagues on nurses' well-being and psychological distress are partially
mediated, that is, reduced, by nurses' overcommitment. Social work environment is
highly important in relation to nurses' well-being and psychological distress.
PMID- 28403080
TI - Characteristics of diurnal ventricular premature complex variation in right
ventricular outflow tract arrhythmias after catheter ablation.
AB - Diurnal variations in ventricular tachyarrhythmias (VAs) have been demonstrated
in idiopathic arrhythmogenic heart disease. The electrophysiological
characteristics of diurnal variations in idiopathic right ventricular outflow
tract (RVOT) VA have not previously been elucidated. Sixty-two consecutive
patients undergoing catheter ablation for idiopathic RVOT VA (mean age: 42.8 +/-
12.3 years, 35 females) were enrolled. The diurnal variation type (group 1, n =
36) was defined as those patients who had most ventricular premature contractions
(VPCs) during the night hours by preprocedure Holter recordings. Group 2 (n = 26)
was defined as those patients who did not have significant VPC variations. The
baseline characteristics and electrophysiological properties were collected and
analyzed, and the rates of recurrence after catheter ablation were compared
between the 2 groups. In this study, heart rate variability analysis demonstrated
lower low frequency/high frequency ratios in group 1 than in group 2 (3.95 +/-
3.08 vs 6.26 +/- 5.33; P = 0.042). There were no significant differences in
baseline characteristics, echocardiography and electrophysiological
characteristics between the 2 groups. During a mean follow-up period of 13.5 +/-
11.0 months, a total of 16 patients had VA recurrences, including 13 patients
from group 1 and 3 patients from group 2 (36.1% vs 12.5%, P = 0.039). This study
demonstrated the effect of the autonomic nervous system in idiopathic RVOT VAs
and that the diurnal variation type leads to a higher recurrence rate after
catheter ablation.
PMID- 28403081
TI - Evaluation of extrapancreatic inflammation on abdominal computed tomography as an
early predictor of organ failure in acute pancreatitis as defined by the revised
Atlanta classification.
AB - The aim of the study was to determine whether extrapancreatic inflammation on
computed tomography (EPIC) is helpful in predicting organ failure in the early
phase of acute pancreatitis (AP) as defined by the 2012 revised Atlanta
classification.Patients (n = 208) who underwent abdominal computed tomography
(CT) within 24 hours after AP onset and admission were retrospectively
identified. Each patient's EPIC score, Balthazar score, bedside index of severity
in acute pancreatitis (BISAP), and systemic inflammatory response syndrome (SIRS)
score were obtained. Primary endpoints were organ failure occurrence and death.
Scores were evaluated by receiver operator characteristic (ROC) curve and area
under the curve (AUC) analysis.Median age was 45 years (range: 18-83 years).
Forty-seven patients (22.6%) developed organ failure, and 5 patients (2.4%)
developed infection and underwent surgery. Two patients died. The median EPIC
score was 2 (range: 0-7). EPIC score accuracy (AUC = 0.724) in predicting organ
failure was similar to that of BISAP (0.773) and SIRS (0.801) scores, whereas
Balthazar scoring was not significant (P = .293). An EPIC score of 3 or greater
had a sensitivity and specificity of 80.65% and 63.16%, respectively. EPIC scores
correlated moderately with organ failure severity (Spearman r = 0.321) and number
of failed organs (r = 0.343).The EPIC scoring system can be useful in predicting
the occurrence of organ failure, but it does not differentiate severity and
number of failed organs in early phase AP.
PMID- 28403082
TI - Metronomic oral cyclosphosphamide as third-line systemic treatment or beyond in
patients with inoperable locoregionally advanced recurrent or metastatic
nasopharyngeal carcinoma.
AB - There is no standard third-line or further systemic treatment for patients with
inoperable locoregionally advanced recurrent or metastatic nasopharyngeal
carcinoma (NPC). Metronomic oral cyclophosphamide provides an acceptable and
cheap option for these heavily pretreated patients who had limited choices. We
conducted a prospective phase II single-arm open-label study of metronomic oral
cyclophosphamide. Patients with locoregionally advanced recurrent inoperable
(rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had Eastern Cooperative Oncology
Group (ECOG) performance status (PS) (0-2) and had progressed after at least 2
lines of palliative systemic chemotherapy were eligible. They received oral
cyclophosphamide between 50 and 150 mg once daily until progressive disease or
unacceptable toxicity. Objective response rate (ORR), disease control rate (DCR),
biochemical response (two consecutive declines of plasma EBV DNA after
treatment), progression-free survival (PFS), overall survival (OS), and safety
profiles were evaluated. A total of 56 patients were recruited. Thirty-three, 13,
6, 3, and 1 patients received cyclophosphamide as 3rd, 4th, 5th, 6th, and 7th
line of therapy respectively. After a median follow-up of 9.95 months (range 1.76
59.51 months), the ORR was 8.9% and the DCR was 57.1%. The median PFS and OS were
4.47 and 9.20 months, respectively. Those with PS 1 had longer median PFS (5.49
months) compared to those with PS 2 (3.75 months, P = .011). Besides, those who
had locoregionally recurrent disease had better PFS (8.97 months, 95% CI, 0.53
17.41 months) compared to those who had distant metastases (4.14 months, 95% CI,
2.53-5.75 months, P = .020). Multivariable analysis revealed that PS 1 (vs 2) (P
= .020) and locoregional recurrence (vs metastasis) (P = .029) were the only
significant independent prognostic factors of PFS. Around 16 (28.6%) patients
developed grade >=3 adverse events, including malaise (5.4%), hematological
(8.9%), gastrointestinal (3.6%), feverish (3.6%), and hemorrhagic (1.8%) events.
The median cost of the whole drug treatment was 51.65 US dollars (USD) (range
4.15-142.75 USD) (1 USD = 7.8 HK dollars [HKD]). Metronomic oral cyclophosphamide
is an acceptable third-line or beyond systemic therapy for locoregionally
advanced recurrent or metastatic NPC with acceptable toxicity and limited
financial burden.
PMID- 28403083
TI - Subclinical hypothyroidism and the risk of chronic kidney disease in T2D
subjects: A case-control and dose-response analysis.
AB - Evidence indicated a positive association between subclinical hypothyroidism
(SCH) and cardiovascular diseases. But the relationship between SCH and chronic
kidney diseases (CKD) remains unclear. A case-control study was performed to
ascertain this relationship followed by a meta-analysis. In this hospital-based,
case-control study, we recruited 3270 type 2 diabetic patients with euthyroidism
and 545 type 2 diabetic patients with SCH. All English studies were searched upon
the relationship between SCH and CKD up to October 2016. Meta-analysis was
performed using STATA 13.0 software. Our case-control study indicated an
association between SCH and CKD in patients with type 2 diabetes [OR (95% CI):
1.22 (1.09-1.36)]. Five observational studies reporting risk of CKD in SCH
individuals were enrolled. A significant relationship between SCH and CKD was
shown [pooled OR 1.80, (95% CI) 1.38-2.35]. Among normal TSH range, individuals
with TSH >=3.0 MUIU/ml had a significantly higher rate of CKD (Fisher exact test,
P = 0.027). Dose-response linear increase of CKD events was explored [pooled OR
1.09 (95% CI): 1.03-1.16 per1 mIU/L increase of TSH]. The present evidence
suggests that SCH is probably a significant risk factor of CKD in T2D. Linear
trend is shown between TSH elevation and CKD in T2D. This relationship between
serum TSH and renal impairment in type 2 diabetic patients needs further studies
to investigate.
PMID- 28403084
TI - The comparative preemptive analgesic efficacy of addition of vitamin B complex to
gabapentin versus gabapentin alone in women undergoing cesarean section under
spinal anesthesia: A prospective randomized double-blind study.
AB - BACKGROUND: Development of new multimodal analgesic regimens have led to
substantial improvement in postoperative pain relief. We designed this study to
compare the effect of combined vitamin B complex-gabapentin versus gabapentin
alone on postoperative pain in women undergoing cesarean section under spinal
anesthesia. METHODS: One hundred twenty-eight women who underwent cesarean
section under spinal anesthesia were randomized to receive orally 300 mg
gabapentin (group G) or 300 mg of gabapentin plus 2 vitamin B complex (group GB)
tablets 30 minutes before surgery. Postoperative pain intensity and total
analgesic consumption during 12 hours after surgery, vomiting, and drowsiness
during recovery were assessed. RESULTS: The pain intensity in the gabapentin plus
vitamin B complex group was lower than gabapentin group during 12 hours after
surgery (95% CI: 1.4-2.2; P < .001). Meanwhile, the total analgesic consumption
in this group was less than gabapentin alone (95% CI: 1.07-1.24; P = 0.034). The
incidence of vomiting in patients who receive combined gabapentin-vitamin B
complex group was similar to gabapentin alone (P = .206). The difference of the
distribution of the relative frequency of sedation according to Ramsay sedation
scores in patients between 2 groups were insignificant (P = .82). All newborns in
our study were free of any adverse effects. CONCLUSION: Addition of vitamin B
complex to gabapentin reduced intensity of postoperative pain and also the total
amount of analgesic consumption within the first 12 hours postoperative following
cesarean section.
PMID- 28403085
TI - Is rotavirus still a major cause for diarrheal illness in hospitalized pediatric
patients after rotavirus vaccine introduction in the Saudi national immunization
program?
AB - Previous studies in Jeddah, western Saudi Arabia, showed rotavirus (RV)
prevalence around 40% in pediatric inpatients with gastroenteritis (GE) with a
maximum level during cooler months. Currently, there are no data on impact of
rotavirus vaccine (RVV) on RV-GE in Saudi Arabia. Therefore, this study was
conducted to assess impact of RVV on incidence and severity of RV-GE in
hospitalized pediatric patients; 3 years after introduction of RVV in Saudi
immunization program (SIP) in January, 2013.This cross-sectional observational
study included GE cases under 5 years of age admitted to 2 tertiary hospitals, in
Jeddah, from October to December, 2015. All included GE-cases had RV antigen
detection in stool by immunochromatographic assay, complete data collection
including RVV status and severity assessment (Vesikari score) in initial
admission.During study period, a total of 359 GE cases in children under 5 years
of age were hospitalized with 14 (3.9%) RV-GE confirmed cases. Mean age of RV-GE
patients was 13.10 +/- 5.70 months. All RV cases had severe GE and 1 case
received RVV. Among other 345 GE cases, 35.7% did not receive RVV and 46.1% had
severe GE. Severe GE (Vesikari score > 11) was more significantly identified
among RV-GE cases than in other all-cause GE (P < .001). During same period of
this study in 2012, 369 RV-GE out of 1193 total GE cases (31%) were hospitalized
at 2 hospitals, so, number of hospitalized pediatric patients for all-cause and
RV-GE in children under 5 years of age decreased significantly in 2015 RV season
(compared to 2015 RV season, odds ratio for RV-GE in 2012: 11.04, 95% CI: 6.38
19.09).Logistic regression analysis of variables of this cross-sectional,
hospital-based study in Jeddah, Saudi Arabia, 3 years after introduction of RVV
in SIP, showed that among the studied variables, RVV was associated with
remarkable reduction of hazard of all-cause and RV-GE in vaccinated and even in
unvaccinated children under 5 years of age possibly by RVV herd effect. However,
RV was still associated with severe GE-related hospitalizations in unvaccinated
children against RV who were younger than 2 years and particularly in the 1st
year of life, indicating need for more optimum rate of RVV coverage. Hopefully,
further improvement in RVV coverage rate may make RV-GE a disease of the past in
Saudi children.
PMID- 28403086
TI - A case report of apatinib in treating osteosarcoma with pulmonary metastases.
AB - RATIONALE: Osteosarcoma is the most common malignant bone tumor in children and
adolescents. Pulmonary metastases lead to a significantly increased risk of
death. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor
targeting the intracellular domain of vascular endothelial growth factor receptor
2 (VEGFR-2), shows survival benefits in treating advanced or metastatic gastric
adenocarcinoma, non-squamous non-small cell lung cancer and metastatic breast
cancer. However, its efficacy in metastatic osteosarcoma has not been reported
yet. PATIENT CONCERNS: Herein, we presented a 50-year-old man patient who visited
hospital due to local bone pain in the left leg. DIAGNOSES: He was initially
diagnosed with osteoblastic osteosarcoma. INTERVENTIONS: The patient suffered
repeated resection surgeries but developed multiple lung metastases. Positive
staining for CD31, CD34, and VEGFR-2 were detected in the tumor section. As he
refused to receive chemotherapy due to concerns regarding the chemotherapy
toxicities and sorafenib due to high cost, apatinib was given at a dose of 500 mg
daily. OUTCOMES: Eleven months following apatinib administration, the patient
achieved a partial response according to the RECIST 1.1 standard. No severe
toxicity or drug-related side effect was observed during the treatment. LESSONS:
Therefore, apatinib could be a new option for the treatment of metastatic
osteosarcoma. Clinical trials are required to further confirm the efficacy and
safety of apatinib in treating pulmonary metastases from osteosarcoma.
PMID- 28403087
TI - Increased BDNF may not be associated with cognitive impairment in heroin
dependent patients.
AB - A growing number of evidence suggests that brain-derived neurotrophic factor
(BDNF) plays an important part in modulating the activities on the basis of
hippocampus neural plasticity, such as learning and memory. Heroin addiction has
a series of cognitive impairments that may be associated with BDNF. In this
study, we explored the association of BDNF with cognitive function in heroin
dependent patients.We enrolled 86 heroin-dependent patients and 238 normal
control subjects and examined their cognition by the repeatable battery for the
assessment of neuropsychological status (RBANS) and serum BDNF levels in 2
groups.BDNF levels were significantly higher in patients than controls (P <
.001). Cognitive scores of the RBANS showed that attention and language index (P
< .05) were significantly lower in heroin-dependent patients than control groups.
Unfortunately, we found no positive association between BDNF and cognitive
function in patients, except that BDNF was positively associated with
visuospatial/constructional index in control groups.Our findings suggest that
BDNF may not be involved in the pathophysiology of heroin dependence, but more
studies about cognitive impairment in heroin addiction are needed.
PMID- 28403088
TI - Changes of transforming growth factor beta 1 in patients with type 2 diabetes and
diabetic nephropathy: A PRISMA-compliant systematic review and meta-analysis.
AB - BACKGROUND: The existing evidence indicates increased levels of transforming
growth factor beta 1 (TGF-beta1) in patients with type 2 diabetes mellitus (T2DM)
and those with type 2 diabetic nephropathy (T2DN); yet no meta-analysis displays
a reliable result. Here we conducted a meta-analysis to evaluate characteristic
changes of TGF-beta1 in T2DM and diabetic nephropathy. METHODS: A systematic
search was conducted for eligible studies, which reported the association of TGF
beta1 withT2DM and T2DN patients, in PubMed, Wangfang, Chinese-Cqvip, and China
National Knowledge Infrastructure database, from February 1, 1991 to December 15,
2015. The association of serum and urine TGF-beta1 in T2DM and T2DN patients
should be evaluated in case-control studies. The Newcastle-Ottawa Scale was used
to access the quality of the included studies, and pooling data were synthesized
as standard mean difference (SMD) and 95% confidence interval (CI). The collected
data were synthesized according to Cochrane Handbook for Systematic Reviews
criteria. Subgroup analysis was conducted by albuminuria and ethnicity.
Regression analysis and sensitivity analysis were used to explore the sources of
heterogeneity. Publication bias was judged by the Egger test. RESULTS: Sixty
three case-control studies of 364 T2DM patients (1604 T2DN patients) and 2100
healthy controls were included for meta-analysis. Compared with the controls, the
cases had increased TGF-beta1 levels in both serum (T2DM: SMD 1.78 MUg/L; 95% CI
0.98-2.59, P < .001; T2DN: SMD 4.70 MUg/L, 95% CI 3.55-5.85, P < .001) and urine
samples (T2DM: SMD 1.27 pg/mg.creatinine, 95% CI 0.16-2.38, P < .001; SMD 1.19
ng/L, 95% CI 0.77-1.62, P < .001; T2DN: SMD 3.14 pg/mg.creatinine, 95% CI 2.15
4.13, P < .001; SMD 4.50 ng/L, 95% CI 3.16-5.83, P < .001). The increase of serum
TGF-beta1 persisted in patients with either microalbuminuria or macroalbuminuria
(all P < .001) in Chinese and non-Chinese population. High heterogeneity exists
in some comparisons and small-sample studies. CONCLUSIONS: Patients with T2DM and
those with albuminuria, Chinese or non-Chinese, had increased serum and urine TGF
beta1 levels.
PMID- 28403089
TI - Clinicopathological characteristics and treatment strategies for patients with
low-grade endometrial stromal sarcoma.
AB - To investigate and evaluate the clinicopathological characteristics and treatment
strategies for patients with low-grade endometrial stromal sarcoma (LG-ESS).The
medical records of LG-ESS patients who were treated at 2 cancer referral centers
from January 2005 to December 2015 were retrospectively reviewed.Twenty patients
with LG-ESS met the inclusion criteria and were included in this analysis.
Hysterectomy with bilateral salpingo-oophorectomy was the mainstay of surgery.
Lymphadenectomy was performed in 12 (60%) cases, and no positive nodes were
identified. CD10 was the most commonly used immunohistochemistry marker, followed
by smooth muscle actin (SMA), estrogen receptor (ER), desmin, progesterone
receptor (PR), and S-100; the positivity rates of these markers were 88.2%,
66.7%, 75.0%, 16.7%, 88.9%, and 0, respectively. Postoperative chemotherapy,
radiotherapy, and hormonal treatment were provided alone or in combination in 10
(50%) patients, 4 (20%) patients, and 1 (5%) patient, respectively. One patient
developed lung metastasis at initial diagnosis, and 2 (10%) patients had
recurrence with distant metastasis. They all underwent complete or incomplete
resection followed by hormonal treatment. The overall survival time of these
patients was 66, 89, and 109 months at last contact, respectively. The 5-year and
10-year disease-free survival rates for the entire cohort were 90% and 72%,
respectively. No patients died of the disease.CD10/SMA/ER/PR in combination with
desmin/S-100 might improve the diagnostic accuracy. Surgical resection is the
foremost treatment for LG-ESS patients with recurrence or distant metastasis.
Hormonal treatment may be beneficial for unresectable or residual tumors.
PMID- 28403090
TI - Anemia, bilirubin, and cardiovascular autonomic neuropathy in patients with type
2 diabetes.
AB - To investigate the relationship among anemia, physiological serum bilirubin
levels, and cardiovascular autonomic neuropathy (CAN) in subjects with type 2
diabetes. In total, 2230 subjects with type 2 diabetes were evaluated in this
cross-sectional study. CAN was diagnosed with a cardiovascular reflex test. The
prevalence of anemia was greater in subjects with CAN. In multivariable analysis,
the relationship between anemia and CAN remained statistically significant after
adjusting for the risk factors (odds ratio [OR] 1.39; 95% confidence interval
[CI] 1.07-1.80, P = .015). Additional adjustment for serum bilirubin
concentrations abolished this relationship (OR 1.20, 95% CI 0.91-1.58, P = .189).
Anemia is positively associated with the prevalence of CAN in subjects with type
2 diabetes. In addition, our results suggest that the putative increased CAN risk
associated with anemia might be mediated by a correlated decrease in serum
bilirubin levels.
PMID- 28403091
TI - Effects of preoperative chronic hypoxemia on geriatrics outcomes after hip
arthroplasty: A hospital-based retrospective analysis study.
AB - The partial pressure of oxygen decreases as altitude increases, the preoperative
chronic hypoxemia (CH) may have a plausible clinical impact. Risk factors for
postoperative serious adverse events (pSAEs) in patients living in high altitudes
during primary hip arthroplasty (HA) are not clear.This is an observational study
embracing patients from January 1, 2011 to December 31, 2015 at Yan'an Hospital
of Kunming City, a 1338-bed municipal teaching hospital of Kunming Medical
University. Univariate analysis revealed that significant differences between
patients with and without preoperative CH occurred in intraoperative hypotension
(77 [33%] vs 34 [47%], P = .040) and that significant differences between
patients with and without pSAEs occurred in following variables: preoperative CH
(32 [57%] vs 199 [80%], P < .001), intraoperative hypotension (37 [66%] vs 74
[30%], P < .001), highest noradrenaline support (.09 [.01-.21] vs .03 [.01-.05]
MUg/kg/min, P < .001), higher application of general anesthesia (15 [27%] vs 29
[12%], P = .004), and lower of combined-spinal epidural anesthesia (CSEA) (21
[37%] vs 165 [66%], P < .001). The general anesthesia and intraoperative
hypotension remained the independent risk factors for pSAEs (P < .05), while the
preoperative CH presented by decreasing its risk (P < .05).This study suggests
that various intraoperative events including general anesthesia, hypotension were
risk factors for the development of pSAEs. Preoperative CH, presenting with
decreased incidence of intensive care unit (ICU) admission and pSAEs, may mimic
hypoxic preconditioning in organic protection, for which further study is needed
to uncover the underlying mechanisms.
PMID- 28403092
TI - Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper
gastrointestinal hemorrhage or valproate side effect?: Case report and literature
review.
AB - RATIONALE: Postoperative coma is not uncommon in patients after craniotomy. It
generally presents as mental state changes and is usually caused by intracranial
hematoma, brain edema, or swelling. Hyperammonemia can also result in
postoperative coma; however, it is rarely recognized as a potential cause in coma
patients. Hyperammonemic coma is determined through a complicated differential
diagnosis, and although it can also be induced as a side effect of valproate
(VPA), this cause is frequently unrecognized or confused with upper
gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein
present a case of valproate-induced hyperammonemic encephalopathy (VHE) to
illustrate the rarity of such cases and emphasize the importance of correct
diagnosis and proper treatment. PATIENT CONCERNS AND DIAGNOSES: A 61-year-old
woman with meningioma was admitted into our hospital. Radical resection of the
tumor was performed, and the patient recovered well as expected. After
administration of valproate for 7 days, the patient was suddenly found in a deep
coma, and her mental state deteriorated rapidly. The diagnoses of hepatic
encephalopathy was confirmed. However, whether it origins from upper
gastrointestinal hemorrhage or valproate side effect is uncertain. INTERVENTIONS
AND OUTCOMES: The patient's condition fluctuated without improvement during the
subsequent 3 days under the treatment of reducing ammonia. With the
discontinuation of valproate treatment, the patient regained complete
consciousness within 48 hours, and her blood ammonia decreased to the normal
range within 4 days. LESSONS SUBSECTIONS: VHE is a rare but serious complication
in patients after craniotomy and is diagnosed by mental state changes and
elevated blood ammonia. Thus, the regular perioperative administration of VPA,
which is frequently neglected as a cause of VHE, should be emphasized. In
addition, excluding UGH prior to providing a diagnosis and immediately
discontinuing VPA administration are recommended.
PMID- 28403093
TI - Jejunojejunal intussusception after Roux-en-Y gastric bypass in a situs inversus
totalis patient: A case report.
AB - INTRODUCTION: Situs inversus totalis (SIT) is an uncommon clinical manifestation.
Patients with SIT typically have malformation in the thorax and abdomen. The
incidence of SIT ranges from 1/10,000 to 1/20,000 (Al-Jumaily and Hoche. J
Laparoendosc Adv Surg Tech A 2001;11:229). Jejunojejunal intussusception is a
rare complication after Roux-en-Y gastric bypass. Intussusception in adult cases
accounts for 5% of adult intestinal obstruction cases, while in children, the
occurrence is high and the majority of them are idiopathic cases. CASE REPORT:
Here, we present an uncommon case of jejunojejunal intussusception after Roux-en
Y gastric bypass in an SIT patient. We performed reduction at the beginning and
resection was done finally. DISCUSSION: We explore the potential causes and
discuss the diagnosis and therapy. CONCLUSION: Intussusception in an SIT patient
is an uncommon case. The symptoms are vague, and it is difficult to diagnose.
Clinicians should be vigilant postoperatively, especially when abdominal pain
after gastrointestinal surgery occurs. It is a rare case worth learning.
PMID- 28403094
TI - Less invasive management of deep neck infection and descending necrotizing
mediastinitis: A single-center retrospective study.
AB - By a 7-year retrospective review, we reported our experience in management of
descending necrotizing mediastinitis (DNM) and deep neck infection (DNI). A
retrospective design was used to reveal the clinical characteristics of DNI and
DNM. The clinical outcome was analyzed to validate less invasive management. We
reviewed 82 patients between 2009 and 2016, 12 of which were diagnosed as DNM by
clinical and computed tomography findings. A total of 35 patients had relevant
systemic conditions, mainly diabetes mellitus (19 patients). Most cases were
secondary to oropharyngeal or dental infections. All patients underwent
transcervical drainage, and 10 DNM patients were treated with additional closed
thoracic drainage simultaneously. Twenty patients accepted more than 1 operation.
Seven patients died as a result of sepsis and/or multiple organ failure. The
mortality rate in our study was similar to that in other studies. In our opinion,
less invasive therapies are useful to most patients. Transcervical drainage alone
is optimal management for all DNI cases and some DNM cases. Additional closed
thoracic drainage is enough for type I and IIA DNM with pleural effusion or
empyema.
PMID- 28403095
TI - Effects of prostaglandin E1 on reperfusion injury patients: A meta-analysis of
randomized controlled trials.
AB - BACKGROUND: Prostaglandin E1 (PGE1) is widely used as a pretreatment for
myocardial reperfusion injury in animal experiments. However, the
cardioprotective effects of PGE1 in patients have not been established. We
performed a meta-analysis to investigate whether PGE1 is cardioprotective, based
on the reduction of correlative reperfusion injury events (CRIE), major adverse
cardiac events (MACE), and biomarker release in patients with ischemia
reperfusion injury. METHODS: The Medline, EMBASE, and Cochrane databases were
searched for randomized clinical trials confirming the effects of PGE1. Two
investigators independently selected suitable trials, assessed trial quality, and
extracted data. RESULTS: Six studies in patients undergoing percutaneous coronary
intervention (4 studies) and cardiac surgery (2 studies), comprising a total of
445 patients, were included in this review. The results showed that PGE1 reduced
the incidence of CRIE (relative ratio 0.4 [95% confidence interval 0.43, 0.95]),
the incidence of MACE (0.35 [0.17, 0.70]), and the level of troponin T
(standardized mean difference 20.28 [20.47, 20.09]), creatine kinase-MB (-1.74 [
3.21, - 0.27]), interleukin-6 (-1.37 [-2.69, - 0.04]), and interleukin-8 (-2.05 [
2.75, - 1.34]). CONCLUSION: PGE1 may have beneficial effects on myocardial
reperfusion injury in the clinic.
PMID- 28403096
TI - The efficiency and safety of fascia iliaca block for pain control after total
joint arthroplasty: A meta-analysis.
AB - BACKGROUND: This meta-analysis aimed to perform a meta-analysis including
randomized controlled trials (RCTs) to assess the efficiency and safety of fascia
iliaca block (FIB) for pain control in patients undergoing total joint
arthroplasty (TJA). METHODS: A systematic search was performed in Medline (1966
2017.03), PubMed (1966-2017.03), Embase (1980-2017.03), ScienceDirect (1985
2017.03) and the Cochrane Library. Study evaluated the efficiency and safety of
FIB in TJA was selected. Meta-analysis was performed using Stata 11.0 software.
RESULTS: Five randomized controlled trials (RCTs) including 270 patients met the
inclusion criteria. The present meta-analysis indicated that there were
significant differences between groups in terms of visual analog scale (VAS)
score at 12 hours (SMD = -0.544, 95% CI: -0.806 to -0.281, P = .000) and 24 hours
(SMD = -0.519, 95% CI: -0.764 to -0.273, P = .000), morphine equivalent
consumption at 12 hours (SMD = -0.895, 95% CI: -1.164 to -0.626, P = .000) and 24
hours (SMD = -0.548, 95% CI:-0.793 to -0.303, P = .000). In addition, fewer
adverse side effect was identified in FIB groups (RD = -0.139, 95% CI: -0.243 to
0.034, P = .009). CONCLUSION: The application of fascia iliaca block could
significantly reduce VAS scores and morphine consumption at 12 and 24 hours
following total knee and hip arthroplasty. In addition, there were fewer adverse
effects in FIB groups. Due to the limited quality of the evidence currently
available, higher quality RCTs are required.
PMID- 28403097
TI - Predictive factors for surgical outcome in anterior clinoidal meningiomas:
Analysis of 59 consecutive surgically treated cases.
AB - Despite the advances in the microsurgical technique and anatomical understanding
of the anterior and middle skull base, anterior clinoidal meningiomas are still
challenging lesions to resect completely and safely due to their intimate
relationship with vital neurovascular structures. We report predictive factors
for tumor recurrence and postoperative complications based on surgical outcome of
patients with anterior clinoidal meningiomas treated at our institution.Fifty
nine consecutive patients with anterior clinoidal meningioma who were surgically
treated between March, 1993, and July, 2015, were reviewed retrospectively. For
microsurgical tumor removal, orbitocranial or orbitozygomatic (78.0%), extended
pterional (15.3%) and subfrontal approach (6.8%) were performed.The median follow
up duration was 54.1 months. Gross total resection (GTR, Simpson's grade I or II)
was achieved in 38 patients (64.4%). The overall recurrence rate (new lesion in
GTR cases and re-growth in non-GTR cases) was 18.6%. GTR (Hazard ratio [HR]
0.014, 95% confidence interval [CI] 0.001-0.256; P = .004), absence of internal
feeder (HR 0.058, 95% CI 0.004-0.759; P = .030) and benign pathology (WHO grade
I, HR 0.056, 95% CI 0.005-0.674; P = .023) were independent prognostic factors
for recurrence-free. Fourteen patients (23.7%) developed permanent complications.
The most common complication was cranial nerve injury (n = 6; 10.2%), followed by
postoperative hemorrhage/infarction, hydrocephalus and infection. Larger size (>=
40 mm) was significant as an independent predictive factor for permanent
complication (HR 0.139, 95% CI 0.030-0.653; P = .012). Old age (>=60 years, P =
.056) and peritumoral edema (thickness >= 5 mm, P = .303) did not reach
statistical significance in multivariate analysis.In surgical resection of
anterior clinoidal meningiomas, various clinicoradiological factors were related
with resection degree, complication, and progression rate. Although our results
showed acceptable resection degree and morbidity, mortality, and recurrence rate,
compared to the results of past, anterior clinoidal meningioma remain as
neurosurgical challenges because of their close contact to critical vascular and
neural structures.
PMID- 28403098
TI - The effects of body mass index on spirometry tests among adults in Xi'an, China.
AB - Obese people have higher risk of respiratory symptoms. The relationship between
obesity and lung function varies with age, race, and geographical region. The
objective of this study is to examine the effects of body mass index on
spirometric tests among adults in Xi'an city.This is a cross-sectional study.
Pulmonary function testing was conducted on participants recruited from Xi'an,
China between July and August 2012. Force expiratory volume in first second
(FEV1), force vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and
forced expiratory flow at 25-75% (FEF25-75) were measured by portable Spirometer.
Lung function was analyzed according to Chinese standard of general obesity.A
total of 770 subjects were analyzed in this study, of whom 299 were males and 471
were females. FVC% (P = .037) decreased significantly in obese subjects than in
nonobese subjects. FVC% (P = .02) declined significantly in overweight subjects
than in normal subjects. For smoker, FEV1% (P = .03) and FVC% (P = .02) were
lower notably in overweight subjects than in normal subjects. FEV1% (P = .0008),
FVC% (P = .0004), and PEF% (P < .0001) were higher significantly in normal
subjects than in underweight subjects.FVC notably decreased in obese people, not
FEV1, FEV1/FVC, PEF, and FEF25-75. FEV1, FVC, and PEF were higher significantly
in normal subjects than in underweight subjects. FVC is affected by BMI in
diphasic change.
PMID- 28403099
TI - US-guided percutaneous laser ablation of refractory metastatic retroperitoneal
lesions: A care-compliant case report.
AB - RATIONALE: Retroperitoneal metastatic lymph node is rare but severe, which has
important structures like the gastrointestinal tract and large blood vessels
around and may challenge excision, inducing serious complications like
hemorrhage, intestinal adhesion, and even death after injury. PATIENT CONCERNS:
We described the case of a 60-year-old man with a history of right liver
resection in 2010, pulmonary wedge resection in 2012, and transarterial
chemoembolization twice in 2014, in which the postoperative pathology suggested
the mixed liver cancer, and poorly differentiated lung cancer from liver
metastasis. DIAGNOSES: Preoperative magnetic resonance (MR) imaging scan showed a
refractory retroperitoneal metastatic lymph node. INTERVENTIONS: Then this
patient repeatedly received 4 ablations with US-guided laser ablation within a
month. OUTCOMES: After 4 ablations due to residual tumor, MR, and CT images of 5
month follow-up showed the partial response. No obvious side effects were
discovered in this case during these procedures. LESSONS: This suggested US
guided laser ablation appears to be a useful technique for retroperitoneal
metastatic lymph node with poor general condition or those refusing surgical
therapy.
PMID- 28403100
TI - Delayed bilateral vocal cord paresis after a continuous interscalene brachial
plexus block and endotracheal intubation: A lesson why we should use low
concentrated local anesthetics for continuous blocks.
AB - RATIONALE: Recurrent laryngeal nerve block is an uncommon complication that can
occur after an interscalene brachial plexus block (ISB), which may lead to vocal
cord palsy or paresis. However, if the recurrent laryngeal nerve is blocked in
patients with a preexisting contralateral vocal cord palsy following neck
surgery, this may lead to devastating acute respiratory failure. Thus, ISB is
contraindicated in patients with contralateral vocal cord lesion. To the best of
our knowledge, there are no reports of bilateral vocal cord paresis, which
occurred after a continuous ISB and endotracheal intubation in a patient with no
history of vocal cord injury or surgery of the neck. PATIENT CONCERNS: A 59 year
old woman was planned for open acromioplasty and rotator cuff repair under
general anesthesia. General anesthesia was induced following an ISB using 0.2%
ropivacaine and catheter insertion for postoperative pain control. DIAGNOSES:
While recovering in the postanesthesia care unit (PACU), however, the patient
complained of a sore throat and hoarseness without respiratory insufficiency. On
the morning of the first postoperative day, she still complained of mild dyspnea,
dysphonia, and slight aspiration. She was subsequently diagnosed with bilateral
vocal cord paresis following an endoscopic laryngoscopy examination.
INTERVENTIONS: The continuous ISB catheter was immediately removed and the
dyspnea and hoarseness symptoms improved, although mild aspiration during
drinking water was still present. OUTCOMES: On the 4th postoperative day, a
laryngoscopy examination revealed that the right vocal cord movement had returned
to normal but that the left vocal cord paresis still remained. LESSONS: When ISB
is planned, a detailed history-taking and examination of the airway are essential
for patient safety and we recommend that any local anesthetics be carefully
injected under ultrasound guidance. We also recommend the use of low
concentration of local anesthetics to avoid possible paralysis of the vocal cord.
PMID- 28403101
TI - Prognostic value of histological subtype in intraductal papillary mucinous
neoplasm of the pancreas: A retrospective analysis of outcome from one single
center.
AB - We sought to retrospectively analyze the outcomes of patients with intraductal
papillary mucinous neoplasm (IPMN) at our pancreatic surgery center, and to
evaluate the prognostic value of histological subtype.The clinical data of 121
IPMNs treated in our center between 2005 and 2014 were retrospectively analyzed.
Pathological slides were thoroughly reviewed by 2 specialized pathologists.Of the
121 patients, 48, 57, and 16 had main-duct, branch-duct, and mixed type IPMNs,
respectively. Forty-one patients had invasive IPMNs. Histological subtypes
consisted of 35 intestinal (28.9%), 56 gastric (46.3%), 29 pancreatobiliary
(24.0%), and 1 oncocytic type (0.8%). Histological subtype was associated with
radiological type, T stage, and degree of dysplasia (P < .05). No significant
difference in overall survival was observed among the 4 histological subtypes,
regardless of whether we considered all IPMNs (P = .106), or invasive IPMNs only
(P = .828). However, the overall survival was associated with radiological type,
T stage, degree of dysplasia, lymph-node status, and nerve invasion. For invasive
IPMNs, the overall survival was associated with nerve invasion and lymph-node
status; however, the association between nerve invasion and overall survival lost
statistical significance after multivariate analysis.Histological subtype had
limited prognostic value in patients with IPMNs, and the main prognostic factor
for patients with invasive IPMNs was the lymph-node status.
PMID- 28403103
TI - Primary bone lymphoma of radius and tibia: A case report and review of
literature.
AB - RATIONALE: Primary bone lymphoma (PBL) is a rare malignant entity. There is a
better survival of PBL than any other malignant bone tumors and extranodal
lymphomas. PATIENT CONCERNS: We report a rare case of PBL involving radius and
tibia. The patient was a 14-year-old girl with left forearm pain and swelling
after trauma. Six months later after the last chemotherapy and radiotherapy, pain
and swelling of left knee was presented. DIAGNOSES: Radiological imaging revealed
a lytic destruction, periosteal reaction, and pathological fracture of radius and
tibia with soft tissue mass. Surgical biopsy was performed, and the result of
histopathological diagnosis was diffused large B-cell lymphoma (stage IV, group
A). INTERVENTION: Chemotherapy combined with radiotherapy was applied before
curation. LESSONS: Due to its uncommon presentation, PBL should be taken into
consideration if differential diagnosis from other bone tumors is necessary in
clinic.
PMID- 28403102
TI - Mandibular regeneration after immediate load dental implant in a periodontitis
patient: A clinical and ultrastructural case report.
AB - RATIONALE: In this case study, we characterized from radiographic, morphological
and elemental point of view the mandibular reconstruction that occur in patients
affects by periodontitis after application of endosseous titanium implants. In
particular, we verified that the bone load applied by titanium implant was able
to induce the mandibular osteogenic reconstruction. PATIENT CONCERN: A 57-year
old female active smoker with no contraindications for dental implants and 3
unstable dental prostheses, underwent open surgery for the application of
endosseous titanium implants (BANP IMPLANT S.R.L., Milan, MI, Italy) with
Immediate load dental implant technique. At the time of presentation, patient was
under treatment beta- beta-adrenergic agents. DIAGNOSES: Patient was affected by
grade II periodontitis according to Armitage classification. INTERVENTATION:
Patient underwent open surgery for the application of endosseous titanium
implants (BANP IMPLANT S.R.L., Milan, MI, Italy) with Immediate load dental
implant technique. Implant placement was performed under local anesthesia after
premedication with diazepam (0.2 mg/kg), given orally 30 minutes before surgery.
After crestal incision, a meticulous cleaning of the oral cavity was carried out.
We removed necrotic tissues and all inflammatory residues. Then, the bone cavity
was extended gradually, according to the intended implant diameter. Inserted
titanium implants were placed 8-12 mm subcrestally. OUTCOMES: We demonstrated
that the bone load applied by titanium implant was able to induce the mandibular
osteogenic reconstruction in a periodontitis patient. LESSONS: This case study
can lay the foundation to improve understanding of the relationship between the
immediate load dental implant and the mandibular regeneration.
PMID- 28403104
TI - Effect of bipolar pulsed radiofrequency on refractory chronic cervical radicular
pain: A report of two cases.
AB - RATIONALE: Despite undergoing transforaminal epidural steroid injection (TFESI),
many patients complain of persisting cervical radicular pain. For the management
of chronic cervical radicular pain, clinicians are widely applying pulsed
radiofrequency (PRF) stimulation to dorsal root ganglions (DRGs). To enhance the
effect of PRF stimulation, we conducted bipolar PRF stimulation in 2 patients
with chronic cervical radicular pain that was refractory to monopolar PRF and
repeated TFESIs. PATIENT CONCERNS: Patients 1 and 2 presented with a numeric
rating scale (NRS) score of 7 and 6 for chronic cervical radicular pain,
respectively, despite undergoing monopolar PRF and 2 TFESIs. DIAGNOSES: On
cervical magnetic resonance imaging, foraminal stenosis at the right C6-7 and
right central to right foraminal disc protrusion on C6-7 were observed in
patients 1 and 2, respectively. Two patients showed a positive response on
diagnostic right C7 selective nerve root block with 0.5 mL of 1% lidocaine.
INTERVENTIONS: Bipolar PRF stimulation was performed under C-arm fluoroscopy. Two
parallel RF cannulas (less than 1 cm apart) were used for DRG stimulation. The
PRF treatment was administered at 5 Hz and a 5-ms pulsed width for 360 seconds at
45 V with the constraint that the electrode tip temperature did not exceed 42
degrees C. OUTCOMES: At the 2-week and 1-month follow-up, after undergoing
bipolar PRF, the pain of patient 1 was completely relieved, and at 2, 3, and 6
months, the pain was scored as NRS 2. In patient 2, at the 2-week follow-up after
undergoing bipolar PRF, pain severity was reduced from NRS 6 to 2. The effect of
bipolar PRF on patient 2 lasted for at least 6 months. No adverse effects were
observed in either patient. LESSONS: Application of bipolar PRF to DRGs seems to
be an effective and safe technique for treating refractory chronic cervical
radicular pain.
PMID- 28403106
TI - Baseline serum albumin and other common clinical markers are prognostic factors
in colorectal carcinoma: A retrospective cohort study.
AB - The aim of the present study was to define the prognostic role of baseline serum
albumin (BSA) in colorectal cancer (CRC) across tumor-node-metastasis (TNM)
stages and other well defined prognostic factors. Many prognostic models in
medicine employ BSA to define or refine treatments in very specific settings; in
CRC, BSA has been found to be a prognostic factor as well. A retrospective cohort
study of consecutive patients with CRC demonstrated by biopsy, who attended a
cancer center during a 7-year period. Multivariate analysis was utilized to
define prognostic factors associated with overall survival (OS) employing the Cox
model. In this retrospective cohort study, 1465 patients were included; 46.6%
were females and 53.4% males (mean age, 59.1 years). Mean BSA was inversely
correlated with TNM stages. By multivariate analysis, it was an independent
explanatory variable. TNM stages, "R" classification, age, lymphocyte count,
neutrophil/platelet ratio, neutrophil/lymphocyte ratio, platelet/lymphocyte
ratio, postoperative morbidity, and BSA were independently associated with OS.
Morbidities, surgery type, chemotherapy, and radiotherapy were considered
confounders after adjusting by TNM stages. BSA is a significant and independent
prognostic factor in patients with CRC, and its effect is maintained across TNM
strata and other well known clinical prognostic factors. It can be easily used in
prognostic models and should be employed to stratify prognosis in therapeutic
randomized clinical trials.
PMID- 28403105
TI - Optimizing stage of single large hepatocellular carcinoma: A study with subgroup
analysis by tumor diameter.
AB - This study aims to refine the designation for single hepatocellular carcinoma
(HCC) >5 cm by comparing the postresection prognosis of these patients with those
who have a single-tumor <=5 cm and those with stage B.Patients with a single
tumor were classified into subgroups based on diameter. Of the 1132 patients
analyzed, 426 had a single-tumor >2 and <=5 cm; 229, a single-tumor >5 and <=8
cm; 52, a single-tumor >8 and < 10 cm; 150, a single-tumor >=10 cm; and 275,
stage B.Hospital mortality and complications increased with tumor size among the
single-tumor subgroups and median survival decreased with increasing of tumor
size. Overall survival (OS) among patients with a single-tumor >5 cm was
significantly lower than among patients with a single-tumor >2 and <=5 cm (P <=
.001), but significantly higher than among patients with clearly stage B (P <=
.001). Patients with a single-tumor >5 and <=8 cm showed lower OS than patients
with a single-tumor >2 and <=5 cm (P < .001). Patients with a single-tumor >8 and
<10 cm or a single-tumor >=10 cm showed lower OS than patients with a single
tumor >5 and <=8 cm (P = .033 and .006), and similar OS to patients with stage B
(P = .323).Patients with a single-tumor >5 and <=8 cm may be assigned to a new
stage between early and intermediate. Patients with a single-tumor >8 cm may be
assigned to intermediate stage.
PMID- 28403107
TI - Reference interval for the disc-macula distance to disc diameter ratio in a large
population of healthy Japanese adults: A prospective, observational study.
AB - This study presents the calculated reference interval for the disc-to-macula
distance to disc diameter ratio (DM:DD) based on a large population of healthy
Japanese adults.A total of 308 consecutive, healthy Japanese adults were examined
in this prospective observational study. Eighteen subjects were also excluded
because of poor quality of the fundus photograph of one or both eyes; 290 (161
men and 129 women) were included in this study. For each subject, a color fundus
photograph of one eye, either the right or left, was randomly selected and used
for analysis. On the photograph, the distances between the fovea and the nearest
temporal margin of the optic disc (Dft), and the two kinds of disc diameters (D1
and D2), which bisected at right angles and one of which was directed to the
fovea (D1), were measured. DM:DD was estimated using the formula: (2Dft + D1)/(D1
+ D2).The mean +/- standard deviation of DM:DD was 2.91 +/- 0.49 for men and 2.96
+/- 0.54 for women; there was no sex difference (P = .78, Mann-Whitney U test).
Also, almost no relationship was found between DM:DD and age (rho = -.12, P =
.04, Spearman's rank correlation coefficient). The data did not fit a normal
distribution (P < .001, Kolmogorov-Smirnov test). The estimated reference
interval for DM:DD corresponding to the 2.5th and 97.5th percentiles was 2.12 to
4.18.Using a nonparametric approach, the reference interval for DM:DD of a large
population of healthy Japanese adults was calculated to be 2.12 to 4.18,
regardless of age or sex.
PMID- 28403108
TI - Analyses and treatments of postoperative nasal complications after endonasal
transsphenoidal resection of pituitary neoplasms.
AB - In this study, we analyze and discuss the treatments of postoperative nasal
complications after endonasal transsphenoidal resection of pituitary neoplasms
(PNs). We performed 129 endonasal transsphenoidal resections of PNs and analyzed
and treated cases with nasal complications. After endonasal transsphenoidal
resection of PNs, there were 26 cases of postoperative nasal complications
(20.1%), including nasal hemorrhage (4.8%), cerebrospinal fluid rhinorrhea
(6.9%), sphenoid sinusitis (2.3%), atrophic rhinitis (1.6%), olfactory disorder
(1.6%), perforation of nasal septum (0.8%), and nasal adhesion (2.3%). All
patients clinically recovered after therapy, which included treatment of the
cavity through nasal endoscopy, intranasal corticosteroids, and nasal irrigation.
We propose that regular nasal endoscopic review, specific nasal medications, and
regular nasal irrigation can effectively clear nasal mucosal hyperemia-induced
edema and nasal/nasoantral secretions, as well as promote regeneration of nasal
mucosa, prevent nasal adhesion, maintain the sinus cavity drainage, and
accelerate the recovery of the physiological function of the paranasal sinus.
Timely treatment of patients with nasal complications after endonasal
transsphenoidal resections of PNs could greatly relieve the clinical symptoms.
Nasal cleaning is very beneficial to patients after surgery recovery.
PMID- 28403109
TI - Low serum levels of uric acid and albumin in patients with Guillain-Barre
syndrome.
AB - Free radical toxicity due to poorly maintained cellular redox levels is crucial
events that have been associated with the pathogenesis of Guillain-Barre syndrome
(GBS) patients. Uric acid (UA) and albumin correlate with oxidative stress in
some degree. We aimed to evaluate the relationship between GBS and serum levels
of UA and albumin in the present study.The serum levels of UA and albumin were
determined in 203 individuals including 88 patients with GBS and 153 healthy
controls (HC).We found that serum levels of UA and albumin in patients with GBS
were significantly lower than those in HC group. Besides, similar phenomenon was
observed when the male and female subgroups were estimated, respectively.
Additionally, we found that there is no statistic difference among subgroups of
GBS regarding UA and albumin. The univariate analysis revealed that both the high
UA and high albumin were protective factors for patients with GBS (odds ratio
[OR] 0.140; 95% confidence interval [CI]: 0.074-0.264; P < .001 and OR 0.016; 95%
CI: 0.006-0.038; P < .001, respectively). It was further confirmed by the
multivariable logistic regression analysis after adjusting for other potential
confounding factors (OR 0.168; 95% CI: 0.055-0.514; P = .002 and OR 0.027; 95%
CI: 0.011-0.071; P < .001, respectively).In conclusion, we found that patients
with GBS had significantly low serum UA and albumin levels. Moreover, we
demonstrated that both the high UA and high albumin were protective factors for
patients with GBS.
PMID- 28403110
TI - A feasibility study of digital single-operator cholangioscopy for diagnostic and
therapeutic procedure (with videos).
AB - Recently, the novel SpyGlass DS Direct Visualization system (SPY DS) has become
available. This system offers several advantages over the conventional SPYGlass
system. This study evaluated the clinical feasibility and efficacy of diagnostic
and therapeutic procedures for biliary disorder using SPY DS.In this
retrospective study, consecutive patients who had biliary disorder were enrolled
between November 2015 and February 2016. All patients could not be diagnosed or
treated by standard endoscopic retrograde cholangiopancreatography in our
hospital or at another hospital.A total of 28 consecutive patients (21 men and 7
women; median age, 73 years; age range, 55-87 years) were retrospectively
enrolled in this study. Among them, diagnostic procedure was performed in 20
patients, and 8 patients underwent therapeutic procedures. The technical success
rate for diagnostic procedures was 100% (20/20). Diagnostic accuracy was 100%
(19/19). The technical success rate for therapeutic procedures was 88% (7/8).
Among these 8 patients, 4 patients with common bile duct stones underwent
electrohydraulic lithotripsy. One patient successfully underwent guidewire
insertion to remove a migrated plastic stent. The 3 remaining patients underwent
SPY DS to insert a guidewire for left bile duct obstruction and for posterior
bile duct branch. In the patient who underwent guidewire insertion for left
hepatic bile duct obstruction cause by primary sclerosing cholangitis, we could
not advance the guidewire into the left hepatic bile duct. No adverse events were
seen. Median SPY DS insertion time was 21 min (range, 8-32 min).Single-operator
cholangioscopy using SPY DS was feasible and had a marked clinical impact in
patients with biliary disease. Additional case reports and prospective studies
are needed to examine further applications of this system.
PMID- 28403112
TI - Footwear used by older people and a history of hyperkeratotic lesions on the
foot: A prospective observational study.
AB - Inadequate footwear, painful and hyperkeratotic lesions (HL) are an extremely
common problems amongst older people. Such problems increase the risk of falls,
hamper mobility, reduction of quality of life, dignity, and ability to remain
independent. The etiology of painful and feet conditions is poorly understood.To
discover footwear preferences of older people, pain tolerance may favor presence
of HL for the use of inadequate footwear in old age.A sample of 100 participants
with a mean age of 74.90 +/- 7.01 years attended an outpatient clinic where self
reported demographic data, frequency with which they checked their feet were
recorded and measurements were taken of foot sensitivity. Additionally, all
participants' shoes were allocated into optimal, adequate, and dangerous
categories based on design, structural and safety features, and materials.Only
12% of the sample population checked their feet every day, 37% revealed symptoms
of neuropathy, 14% used optimal shoes, and 61% presented HL. In a bivariate
analysis, no significant differences were observed.HL are associated with
inadequate footwear, loss of sensitivity, and low frequency of foot health
checks.
PMID- 28403111
TI - Extracorporeal shock wave therapy is effective in treating chronic plantar
fasciitis: A meta-analysis of RCTs.
AB - BACKGROUND: Plantar fasciitis (PF) is the most common reason for heel pain. The
efficacy of extracorporeal shock wave therapy (ESWT) as an ideal alternative to
conservative treatments and surgery is controversial, and almost all previous
articles compared general ESWT with placebo without indicating the kind of shock
wave. We undertook a meta-analysis to compare the efficacy of general ESWT,
focused shock wave (FSW), and radial shock wave (RSW) with placebo, to assess
their effectiveness in chronic PF. METHODS: The PubMed, Medline, EmBase, Web of
Science, and Cochrane library databases were searched for studies comparing FSW
or RSW therapy with placebo in chronic PF. Clinical outcomes included the odds
ratios (ORs) of pain relief, pain reduction, and complications. Relevant data
were analyzed using RevMan v5.3. RESULTS: Nine studies involving 935 patients
were included. ESWT had higher improvement rates than the placebo group (OR 2.58,
95% confidence interval [CI] 1.97-3.39, P < .00001). ESWT had markedly lower
standardized mean difference than placebo, with heterogeneity observed
(standardized mean difference 1.01, 95% CI -0.01 to 2.03, P = .05, I = 96%, P <
.00001). FSW and RSW therapies had greater therapeutic success in pain relief
than the placebo group (OR 2.17, 95% CI 1.49-3.16, P < .0001; OR 4.63, 95% CI
1.30-16.46, P = .02), but significant heterogeneity was observed in RSW therapy
versus placebo (I = 81%, P = .005). CONCLUSION: This meta-analysis suggested that
FSW therapy can relieve pain in chronic PF as an ideal alternative option;
meanwhile, no firm conclusions of general ESWT and RSW effectiveness can be
drawn. Due to variations in the included studies, additional trials are needed to
validate these conclusions.
PMID- 28403113
TI - Incidence of persistent postoperative pain after hepatectomies with 2 regimes of
perioperative analgesia containing ketamine.
AB - Studies designed to assess persistent postoperative pain (PPP) incidence after
hepatectomies are lacking. Our aim was to assess PPP incidence 6 months after
hepatectomies with intravenous (IV) or epidural (EPI) analgesia containing
ketamine.Prospective observational comparative study between 2 cohorts of
patients submitted to hepatectomy. Patients received 1 of 2 analgesic regimes
containing ketamine: EPI group or IV group. Visual analog scale (VAS),
Neuropathic Pain Symptom Inventory (NPSI), Pain Catastrophizing Scale (PCS), and
quantitative sensorial testing (QST: to determine area of hyperalgesia/allodynia)
were assessed preoperatively and postoperatively at 2 h, 24 h, 7 days, 1 month,
and 6 months. VAS >= 1 at 1 and 6 months was considered indicative of PPP and VAS
> 3 was considered as not controlled pain. Side effects and complications were
registered.Forty-four patients were included: 23 in EPI group and 21 in IV group.
Patients in IV group were older and had more comorbidities. No patient presented
VAS > 3 at 1 or 6 months. VAS >= 1 at 1 and 6 months was 36.4% and 22.7%,
respectively. No differences in VAS, NPSI, or PCS were found between groups.
Allodynia/hyperalgesia area did not differ between groups and was infrequent and
slight. Pain pressure threshold in the wound vertical component was significantly
higher in EPI group after 7 days. IV group showed more cognitive side
effects.Incidence of PPP at 6 months after open hepatectomies with EPI or IV
analgesia containing ketamine was lower than previously reported for other
abdominal surgeries.Ketamine influence on low PPP incidence and hyperalgesia
cannot be discarded.
PMID- 28403114
TI - Prevalence of inappropriate antibiotic prescriptions after the great east Japan
earthquake, 2011.
AB - Few studies have investigated the appropriateness of antibiotic use in
postdisaster settings. We retrospectively evaluated clinical databases on health
care delivered at clinics near shelters set up after the Great East Japan
Earthquake, 2011. We defined appropriate, acceptable, and inappropriate
antibiotic use for each diagnostic category, by applying and adopting precedent
studies and clinical guidelines. From March to July, 2011, a total of 23,704
clinic visits occurred at 98 shelters with 7934 residents. Oral antibiotics were
prescribed a total of 2253 times. The median age of the patients was 48.5 years
old (range 0-97), and 43.7% were male. Of 2253 antibiotic prescriptions, 1944
were judged to be inappropriate (86.3% 95% CI 84.8%-87.7%). The most prescribed
antibiotic was clarithromycin (646 times, 28.7%), followed by cefcapene pivoxil
(644 times, 28.6%), levofloxacin (380, 16.9%), cefdinir (194, 8.6%), and
cefditren pivoxil (98, 4.4%). The most frequent diagnosis for which antibiotics
were prescribed was upper respiratory infection (URI, 1040 visits, 46.2%),
followed by acute bronchitis (369, 16.4%), pharyngitis (298, 13.2%), traumatic
injuries (194, 8.6%), acute gastroenteritis (136, 6.0%), urinary tract infections
(UTIs, 123, 5.5%), and allergic rhinitis (5.1%). The majority of antibiotics
prescribed at clinics after the Great East Japan Earthquake was inappropriate.
Significant improvement of the use of antibiotics in postdisaster settings should
be sought immediately in Japan.
PMID- 28403115
TI - Predicted patient demand for a new delivery system for glaucoma medicine.
AB - Sustained-release drug delivery systems that replace the need for daily glaucoma
medications will improve outcomes for those who are nonadherent and reduce the
inconvenience of having to take medications on a recurring basis.The objective is
to estimate uptake (i.e., demand) for a new technology that delivers sustained
release glaucoma medication and to investigate how uptake varies by product
attributes, physician recommendations, peer adoption (i.e., percentage of
patients seen in a clinic using the new technology), and patient
characteristics.In a web-enabled discrete-choice experiment survey, glaucoma
patients in the United States were asked to choose between continuing eye drop
use or purchasing the new delivery system. In a cross-sectional web-enabled
survey, ophthalmologists were asked their likelihood of recommending the new
technology based on product and patient characteristics.Study participants were
500 glaucoma patients who were on topical administration of daily eye drops and
155 ophthalmologists who practice in the US.Main outcomes were predicted uptake
for patients and likelihood of recommending a new drug delivery system for
ophthalmologists. Logistic models were used to analyze the choice data.Uptake was
estimated to be 18% at an annual cost of $1000 and to be 24% when the cost was
$500. A physician's recommendation increased uptake by 6% to 12%, whereas an
increase in peer adoption from 5% to 50% increased uptake by 3% to 7%. Patients
aged >= 65 and those with lower income were more likely to remain on eye drops.
Physicians were more likely to recommend a product if the interval between
administrations is 6 months or longer and when long-term safety and efficacy data
are available. They were less likely to recommend it to patients with lower
income and no adherence problems.Results suggest a significant interest in an
injectable solution or other sustained-release alternatives to daily eye drops.
However, in this survey, patient uptake was greatly influenced by out-of-pocket
cost and the interval between treatment administrations. Few physicians were
willing to recommend sustained-release technology if the treatment interval was
less than 3 months.
PMID- 28403116
TI - Influence of occupation and education level on breast cancer stage at diagnosis,
and treatment options in China: A nationwide, multicenter 10-year epidemiological
study.
AB - The objective of this study was to evaluate the impact of occupation and
education level of Chinese female breast cancer patients on their cancer staging
at diagnosis, clinical and pathological features, rate of implementation, and
selection of treatment.The medical charts of 4211 confirmed female breast cancer
cases diagnosed between 1999 and 2008, from 7 breast cancer centers spread across
the whole of China, were reviewed. Data including information on the patient's
sociodemographic status, clinical and pathological characteristics,
implementation of clinical examination and treatment modalities were analyzed. In
parallel, the associations between different occupations and level of educational
attainment were analyzed in relation to tumor stage through TNM staging, clinical
and pathological characteristics, implementation of clinical examination, and
treatment patterns. Multivariate logistic regression was used to identify whether
the occupation and education level of patients are independent factors of TNM
staging at diagnosis.There were significant differences among different
occupation groups and the education level of patients in regards to pathological
characteristics and treatment choice. Both the occupation and education level of
patients were independent factors of TNM staging at diagnosis. For patients
within the lower-income occupation or lower educational attainment group, the
tumor stage was later, the rates of implementation of relevant investigations
were lower, as were the rates of radiotherapy, chemotherapy, and endocrine
therapy.This study suggests that strategies should work toward developing more
accurate and effective breast cancer prevention and treatment strategies aimed
specifically at patients with lower educational attainment levels and at specific
occupation groups.
PMID- 28403117
TI - Association of the ACE, GSTM1, IL-6, NOS3, and CYP1A1 polymorphisms with
susceptibility of mycoplasma pneumoniae pneumonia in Chinese children.
AB - Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) and
the clinical presentation of mycoplasma pneumoniae pneumonia (MPP) varies widely.
Genetic variability affecting the host response may also influence the
susceptibility to MPP. Several studies have investigated the association between
single nucleotide polymorphism (SNP) of some genes and the risks of CAP; however,
the results were inconsistent. Here, we investigated the association of 5
functional genes and the risks of MPP, including ACE (rs4340), GSTM1 (Ins/del),
IL-6 (rs1800795), NOS3 (rs1799983), and CYP1A1 (rs2606345) in a total of 715
subjects (415 cases, 300 controls) by using tetra-primer allele-specific
polymerase chain reaction (PCR) and Sanger sequencing. The gene-gene interactions
were analyzed using the Multifactor Dimensionality Reduction and cumulative
genetic risk score approaches. Our results showed that 3 SNPs of ACE rs4340, IL-6
rs1800795, and NOS3 rs1799983 were significantly associated with the risks of
MPP, while no differences were observed in genotype frequencies of GSTM1
(Ins/del) and CYP1A1 rs2606345 between both groups. The combinations of ACE
rs4340D/NOS3 rs1799983T/CYP1A1 rs2606345G and ACE rs4340D/NOS3 rs1799983T
contribute to the genetic susceptibility of MPP in Chinese children.
PMID- 28403118
TI - Validation of Intensive Care and Mechanical Ventilation Codes in Medicare Data.
AB - OBJECTIVES: To assess the reliability of codes relevant to critically ill
patients in administrative data. DESIGN: Retrospective cohort study linking data
from Acute Physiology and Chronic Health Evaluation Outcomes, a clinical database
of ICU patients with data from Medicare Provider Analysis and Review. We linked
data based on matching for sex, date of birth, hospital, and date of admission to
hospital. SETTING: Forty-six hospitals in the United States participating in
Acute Physiology and Chronic Health Evaluation Outcomes. PATIENTS: All patients
in Acute Physiology and Chronic Health Evaluation Outcomes greater than or equal
to 65 years old who could be linked with hospitalization records in Medicare
Provider Analysis and Review from January 1, 2009, through September 30, 2012.
MEASUREMENTS AND MAIN RESULTS: Of 62,451 patients in the Acute Physiology and
Chronic Health Evaluation Outcomes dataset, 80.1% were matched with data in
Medicare Provider Analysis and Review. All but 2.7% of Acute Physiology and
Chronic Health Evaluation Outcomes ICU patients had either an ICU or coronary
care unit charge in Medicare Provider Analysis and Review. In Acute Physiology
and Chronic Health Evaluation Outcomes, 37.0% received mechanical ventilation
during the ICU stay versus 24.1% in Medicare Provider Analysis and Review. The
Medicare Provider Analysis and Review procedure codes for mechanical ventilation
had high specificity (96.0%; 95% CI, 95.8-96.2), but only moderate sensitivity
(58.4%; 95% CI, 57.7-59.1), with a positive predictive value of 89.6% (95% CI,
89.1-90.1) and negative predictive value of 79.7% (95% CI, 79.4-80.1). For
patients with mechanical ventilation codes, Medicare Provider Analysis and Review
overestimated the percentage with a duration greater than 96 hours (36.6% vs
27.3% in Acute Physiology and Chronic Health Evaluation Outcomes). There was
discordance in the hospital discharge status (alive or dead) for only 0.47% of
all linked records (kappa = 1.00). CONCLUSIONS: Medicare Provider Analysis and
Review data contain robust information on hospital mortality for patients
admitted to the ICU but have limited ability to identify all patients who
received mechanical ventilation during a critical illness. Estimates of use of
mechanical ventilation in the United States should likely be revised upward.
PMID- 28403120
TI - Detection of Pulmonary Embolism During Cardiac Arrest-Ultrasonographic Findings
Should Be Interpreted With Caution.
AB - OBJECTIVES: The aim of this study was to test the hypothesis that the right
ventricle is more dilated during resuscitation from cardiac arrest caused by
pulmonary embolism, compared with hypoxia and primary arrhythmia. DESIGN: Twenty
four pigs were anesthetized and cardiac arrest was induced using three different
methods. Pigs were resuscitated after 7 minutes of untreated cardiac arrest.
Ultrasonographic images were obtained and the right ventricular diameter was
measured. SETTING: University hospital animal laboratory. SUBJECTS: Female
crossbred Landrace/Yorkshire/Duroc pigs (27-32 kg). INTERVENTIONS: Pigs were
randomly assigned to cardiac arrest induced by pulmonary embolism, hypoxia, or
primary arrhythmia. MEASUREMENTS AND MAIN RESULTS: There was no difference at
baseline. During induction of cardiac arrest, the right ventricle dilated in all
groups (p < 0.01 for all). The primary endpoint was right ventricle diameter at
the third rhythm analysis: 32 mm (95% CI, 29-36) for pulmonary embolism which was
significantly larger than both hypoxia: 23 mm (95% CI, 20-27) and primary
arrhythmia: 25 mm (95% CI, 22-28)-the absolute difference was 7-9 mm. Physicians
with basic training in focused cardiac ultrasonography were able to detect a
difference in right ventricle diameter of approximately 10 mm with a sensitivity
of 79% (95% CI, 64-94) and a specificity of 68% (95% CI, 56-80). CONCLUSIONS: The
right ventricle was more dilated during resuscitation when cardiac arrest was
caused by pulmonary embolism compared with hypoxia and primary arrhythmia.
However, the right ventricle was dilated, irrespective of the cause of arrest,
and diagnostic accuracy by physicians with basic training in focused cardiac
ultrasonography was modest. These findings challenge the paradigm that right
ventricular dilatation on ultrasound during cardiopulmonary resuscitation is
particularly associated with pulmonary embolism.
PMID- 28403119
TI - Combined Measurement of Soluble ST2 and Amino-Terminal Pro-B-Type Natriuretic
Peptide Provides Early Assessment of Severity in Cardiogenic Shock Complicating
Acute Coronary Syndrome.
AB - OBJECTIVES: Mortality in cardiogenic shock complicating acute coronary syndrome
is high, and objective risk stratification is needed for rational use of advanced
therapies such as mechanical circulatory support. Traditionally, clinical
variables have been used to judge risk in cardiogenic shock. The aim of this
study was to assess the added value of serial measurement of soluble ST2 and
amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk
stratification in cardiogenic shock. DESIGN: CardShock (www.clinicaltrials.gov
NCT01374867) is a prospective European multinational study of cardiogenic shock.
The main study introduced CardShock risk score, which is calculated from seven
clinical variables at baseline, and was associated with short-term mortality.
SETTING: Nine tertiary care university hospitals. PATIENTS: Patients with
cardiogenic shock caused by acute coronary syndrome (n=145). INTERVENTIONS: In
this substudy, plasma samples from the study patients were analyzed at eight time
points during the ICU or cardiac care unit stay. Additional prognostic value of
the biomarkers was assessed with incremental discrimination improvement.
MEASUREMENTS AND MAIN RESULTS: The combination of soluble ST2 and amino-terminal
pro-B-type natriuretic peptide showed excellent discrimination for 30-day
mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after
cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated
(soluble ST2, >= 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, >=
4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or
neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined
measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at
12 hours added value to CardShock risk score, correctly reclassifying 11% of
patients. CONCLUSIONS: The combination of results for soluble ST2 and amino
terminal pro-B-type natriuretic peptide provides early risk assessment beyond
clinical variables in patients with acute coronary syndrome-related cardiogenic
shock and may help therapeutic decision making in these patients.
PMID- 28403121
TI - Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With
Emphasis on Rescue Extracorporeal Membrane Oxygenation.
AB - OBJECTIVES: To describe the characteristics, management, and outcome of patients
admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter
retrospective study. SETTING: Fifteen university and nonuniversity ICUs in
France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis.
INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a
median age of 46 years (40-54 yr); 65% were males. At admission, the median
Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified
Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction
was consistently decreased with a median value of 30% (15-40%). Mechanical
ventilation was required in 23 patients, mainly because of congestive heart
failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement
therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as
a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33
of 34 patients. When assayed, urinary metanephrine and catecholamine levels were
consistently elevated. Five patients underwent urgent surgery, including two
during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34),
and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not
significantly different between patients managed with versus without
extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher
severity scores at admission in the extracorporeal membrane oxygenation group.
CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering
this diagnosis and performing abdominal CT in patients with unexplained
cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane
oxygenation and adrenalectomy should be considered as a therapeutic in most
severe cases.
PMID- 28403122
TI - Editorial.
PMID- 28403123
TI - Influence of genetic variations in the SOD1 gene on the development of ascites
and spontaneous bacterial peritonitis in decompensated liver cirrhosis.
AB - BACKGROUND: The balance between generation and elimination of reactive oxygen
species by superoxide dismutase (SOD) is crucially involved in the
pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and
induce inflammation/fibrosis, but also play a critical role in immune defense
from pathogens. As both processes are involved in the development of liver
cirrhosis and its complications, genetic variation of the SOD1 gene was
investigated. PATIENTS AND METHODS: Two SOD1 single nucleotide polymorphisms
(rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver
transplantation. In addition, 344 cirrhotic patients with ascites were analyzed
in a cohort of 521 individuals in terms of the relationship of these
polymorphisms with spontaneous bacterial peritonitis (SBP). RESULTS: Although
rs3844942 showed no associations with complications of cirrhosis, we observed a
significant association between rs1041740 and the presence of ascites and SBP in
the discovery cohort of patients with cirrhosis. Importantly, the association
with SBP was not confirmed in the validation cohort of patients with ascites. By
contrast, a trend toward lower SBP rates was observed in carriers of rs1041740.
In this cohort, rs1041740 was not associated with survival. CONCLUSION: These
data suggest a complex role of SOD1 in different processes leading to
complications of liver cirrhosis. rs1041740 might be associated with the
development of ascites and possibly plays a role in SBP once ascites has
developed.
PMID- 28403124
TI - Association between oral hygiene and ultrasound-confirmed gallstone disease in US
population.
PMID- 28403125
TI - Low vs. high fidelity: the importance of 'realism' in the simulation of a stone
treatment procedure.
AB - PURPOSE OF REVIEW: Simulation training for stone surgery is now increasingly used
as part of training curricula worldwide. A combination of low and high fidelity
simulators has been used with varying degrees of 'realism' provided by them. In
this review, we discuss low and high fidelity simulators used for ureteroscopy
(URS) and percutaneous nephrolithotomy (PCNL) stone procedures with their
advantages, disadvantages and future direction for endourological simulation
surgery. The final goal will be to understand whether or not 'realism' has to be
considered as a critical element in simulation for this field. RECENT FINDINGS:
There is a wide range of simulators available for URS and PCNL training ranging
from basic bench-type model to advanced virtual reality and cadaveric models, all
providing various levels of realism. Although basic models might be more useful
to novices, advanced models allow for complex and more realistic simulation
training. SUMMARY: With a wide variety of simulators now available and given the
latest novelties in modular training curriculums, combination of low and high
fidelity simulators that provide a realistic and cost-effective option seems to
be the way forward. It is unavoidable that simulators will play an increasing
role in endourological training.
PMID- 28403126
TI - Effector Antitumor and Regulatory T Cell Responses Influence the Development of
Nonmelanoma Skin Cancer in Kidney Transplant Patients.
AB - BACKGROUND: Chronic immunosuppression promotes nonmelanocytic squamous cell
carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a
key role controlling tumor growth and are influenced by different
immunosuppressive agents. We hypothesized that functional impairment of tumor
specific T cell responses due to calcineurin inhibitors (CNI) could contribute to
SCC development, whereas conversion to mammalian target of rapamycin inhibitors
(mTOR-i) could recover this protective immune response. METHODS: Peripheral tumor
specific T cell responses against main SCC-derived antigens using the IFN-gamma
enzyme-linked immunospot assay and intratumor (IT) and circulating immune
phenotypes (CD4 + T, CD8 + T, CD20 + B, CD56 + NK, FOXP3 + regulatory T [Treg]
cells) were explored in a cross-sectional analysis in 59 kidney transplant
patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants
developing SCC (NoKT-SCC) and 6 healthy controls. Moreover, 25 KT-CNI-SCC were
switched to mTOR-i and evaluated after 12 months. RESULTS: Kidney transplant
patients showed lower IT infiltrates and tumor-specific T cell responses than
NoKT-SCC, and intratumoral and circulating FOXP3 + Treg cells were higher in KT
mTORi-SCC (P < 0.05). Tumor-specific T cell responses were significantly lower in
KT-CNI-SCC than KT-mTORi-SCC and NoKT-SCC and predicted SCC relapses (area under
the curve = 0.837; P < 0.05). One-year after mTOR-i conversion, a significant
increase in FOXP3 + Treg cell numbers and tumor-specific T cell responses were
observed, reaching similar levels than KT-mTORi-SCC and NoKT-SCC patients.
CONCLUSIONS: Tumor-specific T cell responses are strongly impaired in CNI-treated
patients but recover after mTOR-i conversion, reducing SCC relapses.
PMID- 28403127
TI - A Randomized Controlled Clinical Trial Comparing Belatacept With Tacrolimus After
De Novo Kidney Transplantation.
AB - BACKGROUND: Belatacept, an inhibitor of the CD28-CD80/86 costimulatory pathway,
allows for calcineurin-inhibitor free immunosuppressive therapy in kidney
transplantation but is associated with a higher acute rejection risk than
ciclosporin. Thus far, no biomarker for belatacept-resistant rejection has been
validated. In this randomized-controlled trial, acute rejection rate was compared
between belatacept- and tacrolimus-treated patients and immunological biomarkers
for acute rejection were investigated. METHODS: Forty kidney transplant
recipients were 1:1 randomized to belatacept or tacrolimus combined with
basiliximab, mycophenolate mofetil, and prednisolone. The 1-year incidence of
biopsy-proven acute rejection was monitored. Potential biomarkers, namely,
CD8CD28, CD4CD57PD1, and CD8CD28 end-stage terminally differentiated memory T
cells were measured pretransplantation and posttransplantation and correlated to
rejection. Pharmacodynamic monitoring of belatacept was performed by measuring
free CD86 on monocytes. RESULTS: The rejection incidence was higher in belatacept
treated than tacrolimus-treated patients: 55% versus 10% (P = 0.006). All 3 graft
losses, due to rejection, occurred in the belatacept group. Although 4 of 5
belatacept-treated patients with greater than 35 cells CD8CD28 end-stage
terminally differentiated memory T cells/MUL rejected, median pretransplant
values of the biomarkers did not differ between belatacept-treated rejectors and
nonrejectors. In univariable Cox regressions, the studied cell subsets were not
associated with rejection-risk. CD86 molecules on circulating monocytes in
belatacept-treated patients were saturated at all timepoints. CONCLUSIONS:
Belatacept-based immunosuppressive therapy resulted in higher and more severe
acute rejection compared with tacrolimus-based therapy. This trial did not
identify cellular biomarkers predictive of rejection. In addition, the CD28
CD80/86 costimulatory pathway appeared to be sufficiently blocked by belatacept
and did not predict rejection.
PMID- 28403129
TI - Singing a New SONG: Outcomes for Clinical Trials.
PMID- 28403128
TI - An Oxygenated and Transportable Machine Perfusion System Fully Rescues Liver
Grafts Exposed to Lethal Ischemic Damage in a Pig Model of DCD Liver
Transplantation.
AB - BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after
circulatory death (DCD) would significantly increase the donor pool for liver
transplantation. We aimed to determine whether a novel, oxygenated and
hypothermic machine perfusion device (HMP Airdrive system) improves the quality
of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest
was induced in female large white pigs by intravenous injection of potassium
chloride. After 60 minutes of WI, livers were flushed in situ with histidine
tryptophan-ketoglutarate and subsequently preserved either by simple cold storage
(WI-SCS group) or HMP (WI-HMP group) using Belzer-MPS solution. Liver grafts
procured from heart-beating donors and preserved by SCS served as controls. After
4 hours of preservation, all livers were transplanted. RESULTS: All recipients in
WI-SCS group died within 6 hours after transplantation. In contrast, the HMP
device fully protected the liver against lethal ischemia/reperfusion injury,
allowing 100% survival rate. A postreperfusion syndrome was observed in all
animals of the WI-SCS group but none of the control or WI-HMP groups. After
reperfusion, HMP-preserved livers functioned better and showed less
hepatocellular and endothelial cell injury, in agreement with better-preserved
liver histology relative to WI-SCS group. In addition to improved energy
metabolism, this protective effect was associated with an attenuation of
inflammatory response, oxidative load, endoplasmic reticulum stress,
mitochondrial damage, and apoptosis. CONCLUSIONS: This study demonstrates for the
first time the efficacy of the HMP Airdrive system to protect liver grafts from
lethal ischemic damage before transplantation in a clinically relevant DCD model.
PMID- 28403130
TI - Primary Ectopic Ethmoidal Craniopharyngioma.
AB - Craniopharyngiomas are benign but aggressive epithelial tumors usually
originating in the anterior lobe of the pituitary gland from squamous remnants of
an incompletely involuted craniopharingeal duct developing from the Rathke pouch.
To the authors' knowledge only 1 patient of a primary isolated ethmoidal
craniopharyngioma has been reported in the literature.The authors report the case
of a 17-year-old boy with a primary extracranial ethmoidal craniopharyngioma. An
endoscopic endonasal approach was employed to resect the tumor. After 2 years of
clinical and radiological follow-up no recurrence of disease was observed.Primary
ethmoidal craniopharyngiomas are rare entities and biopsy is necessary for
diagnosis. However, a preoperative assessment by means of nasal endoscopy,
computed tomography scan, and enhanced magnetic resonance imaging is mandatory to
better evaluate the extension and characteristics of the tumor. The endoscopic
endonasal technique is a safe and effective approach for the treatment of these
lesions.
PMID- 28403131
TI - Olfactory Bulb Volume Changes in Patients With Nasal Septal Deviation.
AB - OBJECTIVES: The olfactory bulb (OB) plays a pivotal role in the processing of
olfactory information. The aim of this study was to investigate the OB volume
changes and its possible associations with nasal septal deviation. STUDY DESIGN:
Cross-sectional study. SETTING: Otolaryngology Department of Bozok University
School of Medicine and Neurology Department of Yozgat State Hospital. SUBJECTS
AND METHODS: Ninety patient's cranial magnetic resonance imaging (MRI) studies
(46 males and 44 females, mean age 36 +/- 13.4 years; range 18-56 years) with
isolated nasal septal deviations were recruited for the study. Olfactory bulb
volumes in all study subjects were evaluated in T2-weighted coronal MRI images by
planimetric manual contouring. RESULTS: Nasal septal deviation angles were found
to range between 5 degrees and 23.21 degrees (mean 13.6 degrees +/- 3.58
degrees ). The right-sided deviations included 17 mild (<9 degrees , Group I), 20
moderate (9 degrees -15 degrees , Group II), and 16 severe (15 degrees and up,
Group III) patients. The left-sided deviations included 14 mild (<9 degrees ,
Group I), 13 moderate (9 degrees -15 degrees , Group II), and 10 severe (15
degrees and up, Group III) subjects. Olfactory bulb volumes were calculated in
both right- and left-sided deviation groups. In the patients with left-sided
septal deviations of Groups I, II, and III, the left OB volumes of Groups I, II,
and III were 46.49 +/- 3.87, 47.46 +/- 3.36, and 60.68 +/- 5.65 mm and the right
OB volumes were 53.37 +/- 3.76, 56.47 +/- 4.43, and 76.69 +/- 6.84 mm,
respectively. The statistical evaluation of the right OB volumes did not produce
significant difference between Groups I and II (P = 0.73). The authors
demonstrated statistically significant differences in comparison of Groups I to
III and Groups II to III (P = 0.002 and P = 0.016, respectively). In the right
septal deviation group for Groups I, II, and III, mean volumes of right OB
volumes were 45.59 +/- 4.46, 48.63 +/- 3.78, and 61.35 +/- 5.84 mm, respectively,
and the left OB volumes were 54.67 +/- 4.73, 57.65 +/- 4.53, and 75.84 +/- 7.67
mm, respectively. There was no statistically significant difference between
Groups I and II (P = 0.95) left OB volumes in the right-sided deviation group,
but statistically significant difference was demonstrated in Groups I to III and
Groups II to III compartments (P = 0.002 and P = 0.003). CONCLUSION: In our
study, while mild and moderate septal deviations lacked any significant affect on
OB volumes, severe deviations were found to have significant impact on these
parameter. Additionally the contralateral OB volumes in the severe septum
deviation group were significantly bigger when compared to the ipsilateral OB
volumes. Further multidisciplinary studies are required to evaluate the clinical
significance of OB volume changes in diagnosis and follow-up of several
otolaryngologic or nonotolaryngologic diseases.
PMID- 28403133
TI - Three Skin Zones in the Asian Upper Eyelid Pertaining to the Asian
Blepharoplasty.
AB - BACKGROUND: Natural looking double fold is an essential and aesthetically
pleasing masterpiece in Asian blepharoplasty. This study aims to emphasize the 3
skin zone concept in the Asian upper blepharoplasty. METHODS: The authors
examined the anterior lamella of each skin zone microscopically by performing 31
double-eyelid surgeries and 11 infrabrow lifts. Characteristics of dermal
components, subcutaneous tissue, and outer fascia of OOM (OFOOM) at each skin
zone were documented. The authors evaluated the vertical scales of each skin zone
in young and aged Asian patients who visited the first author's clinic for the
primary or secondary upper blepharoplasty with *3.5 magnifying surgical loupe.
RESULTS: The thickness of OOM had no difference among zones 1, 2, and 3. The skin
and subdermal tissue had varying characteristics according to its skin zone. At
zone 1, it seemed that only thin skin was on the OOM. The anterior lamella of
zone 2 seemed to consist of skin, white fascia (OFOOM) including a venous
network, and OOM in a gross field. At zone 3, thick skin, thick subcutaneous
fatty layer, and OOM were magnified. The OFOOM of zone 3 was not significantly
identified due to a sticky adherence with OOM. At the point of vertical scales of
skin zone, good eyelids have lower zone 3 ratio and higher zones 1 and 2 ratio
with qualified topographic condition. CONCLUSION: The authors classified the
Asian upper eyelid as with 3 skin zones. Based on its anatomical investigation,
the authors can afford anthropometric data and supplemental theory for the
creation of aesthetic folds.
PMID- 28403134
TI - Early, Computer-Aided Design/Computer-Aided Modeling Planned, Le Fort I
Advancement With Internal Distractors to Treat Severe Maxillary Hypoplasia in
Cleft Lip and Palate.
AB - Traditionally, maxillary hypoplasia in the setting of cleft lip and palate is
treated via orthognathic surgery at skeletal maturity, which condemns these
patients to abnormal facial proportions during adolescence. The authors sought to
determine the safety profile of computer-aided design/computer-aided modeling
(CAD/CAM) planned, Le Fort I distraction osteogenesis with internal distractors
in select patients presenting at a young age with severe maxillary retrusion. The
authors retrospectively reviewed our "early" Le Fort I distraction osteogenesis
experience-patients performed for severe maxillary retrusion (>=12 mm underjet),
after canine eruption but prior to skeletal maturity-at a single institution.
Patient demographics, cleft characteristics, CAD/CAM operative plans, surgical
complications, postoperative imaging, and outcomes were analyzed. Four patients
were reviewed, with a median age of 12.8 years at surgery (range 8.6-16.1 years).
Overall mean advancement was 17.95 + 2.9 mm (range 13.7-19.9 mm) with mean SNA
improved 18.4 degrees to 87.4 +/- 5.7 degrees . Similarly, ANB improved 17.7
degrees to a postoperative mean of 2.4 +/- 3.1 degrees . Mean follow-up was
100.7 weeks, with 3 of 4 patients in a Class I occlusion with moderate-term
follow-up; 1 of 4 will need an additional maxillary advancement due to pseudo
relapse. In conclusion, Le Fort I distraction osteogenesis with internal
distractors is a safe procedure to treat severe maxillary hypoplasia after canine
eruption but before skeletal maturity. Short-term follow-up demonstrates safety
of the procedure and relative stability of the advancement. Pseudo-relapse is a
risk of the procedure that must be discussed at length with patients and
families.
PMID- 28403135
TI - Evaluation of Impacting Factors on Facial Bone Thickness in the Anterior
Maxillary Region.
AB - BACKGROUND: The goal of the current study was to measure the width of the labial
alveolar bone of the overlying maxillary anterior teeth, based on cone-beam
computed tomography (CBCT) images, and the distance between cementoenamel
junction (CEJ) and bone crest in adult patients. METHODS: A cross-sectional study
was performed using a sample of 132 tomographic scans. Intact maxillary anterior
with healthy periodontium and teeth was randomly selected and afterwards assessed
by 2 calibrated and independent reviewers. RESULT: The average bone thickness at
2 mm from the CEJ of the maxillary right central incisors was 0.63 +/- 0.69 mm
and over the maxillary left central incisors was 0.59 +/- 0.71 mm. Moreover on
the right and left lateral maxillary incisors, the crestal bone width averaged
0.64 +/- 0.81 and 0.61 +/- 0.7 mm, respectively. Concerning the maxillary canine
region on both sides, the crestal bone thickness averaged 0.72 +/- 0.9 and 0.66
+/- 0.69 mm, in the maxillary right and left the canine regions, respectively.
Furthermore, according to the gender and systemic disease, there were some
recognizable differences in the facial bone thickness between the left and the
right side. CONCLUSIONS: The current study has advocated the outcome of a mostly
thin buccal bone overlying the maxillary anterior teeth; hence, clinicians should
always consider the thickness of the facial cortical plate of the extraction site
and the positioning of the implant placement in the socket.
PMID- 28403136
TI - Influence of CYP2C9 and COX-2 Genetic Polymorphisms on Clinical Efficacy of Non
Steroidal Anti-Inflammatory Drugs in Treatment of Ankylosing Spondylitis.
AB - BACKGROUND The aim of this study was to evaluate the relationships of CYP2C9 and
COX-2 genetic polymorphisms with therapeutic efficacy of non-steroidal anti
inflammatory drugs (NSAIDs) in treatment of ankylosing spondylitis (AS). MATERIAL
AND METHODS We enrolled 130 AS inpatients and outpatients in the Arthritis and
Rheumatism Department of Peking University First Hospital and 106 healthy people
getting routine check-ups between September 2013 and July 2014. CYP2C9 and COX-2
genetic polymorphisms were detected by PCR-RFLP. All AS patients underwent
medical treatment and 12-week follow-up treatment. Score differences of BASDAI,
ASAS20, ASAS50, and ASAS70 for AS patients with different genotypes before and
after treatment were compared. RESULTS In terms of COX-2-1290A/G and -1195G/A
gene polymorphism genotype and allele frequency, the case group and control group
were obviously different (all P<0.05), but CYP2C9*3 polymorphism genotype and
allele frequency were not statistically different between the 2 groups (P>0.05).
AS patients had improved BASDAI, ASAS20, ASAS50, and ASAS70 scores after they
received NSAID treatment (all P<0.05). Furthermore, the efficacy of NSAID in
treatment of AS and COX-2 gene -1290A/G and -1195G/A polymorphism were associated
(all P<0.05), but it is not associated with CYP2C9 *3 polymorphism (all P>0.05).
CONCLUSIONS COX-2-1290A/G and -1195G/A polymorphism may increase AS risk and they
both can be considered as biological indicators for prediction of efficacy of
NSAIDs in treatment of AS.
PMID- 28403137
TI - Topological defects control collective dynamics in neural progenitor cell
cultures.
AB - Cultured stem cells have become a standard platform not only for regenerative
medicine and developmental biology but also for biophysical studies. Yet, the
characterization of cultured stem cells at the level of morphology and of the
macroscopic patterns resulting from cell-to-cell interactions remains largely
qualitative. Here we report on the collective dynamics of cultured murine neural
progenitor cells (NPCs), which are multipotent stem cells that give rise to cells
in the central nervous system. At low densities, NPCs moved randomly in an amoeba
like fashion. However, NPCs at high density elongated and aligned their shapes
with one another, gliding at relatively high velocities. Although the direction
of motion of individual cells reversed stochastically along the axes of
alignment, the cells were capable of forming an aligned pattern up to length
scales similar to that of the migratory stream observed in the adult brain. The
two-dimensional order of alignment within the culture showed a liquid-crystalline
pattern containing interspersed topological defects with winding numbers of +1/2
and -1/2 (half-integer due to the nematic feature that arises from the head-tail
symmetry of cell-to-cell interaction). We identified rapid cell accumulation at
+1/2 defects and the formation of three-dimensional mounds. Imaging at the single
cell level around the defects allowed us to quantify the velocity field and the
evolving cell density; cells not only concentrate at +1/2 defects, but also
escape from -1/2 defects. We propose a generic mechanism for the instability in
cell density around the defects that arises from the interplay between the
anisotropic friction and the active force field.
PMID- 28403138
TI - Bordetella bronchiseptica exploits the complex life cycle of Dictyostelium
discoideum as an amplifying transmission vector.
AB - Multiple lines of evidence suggest that Bordetella species have a significant
life stage outside of the mammalian respiratory tract that has yet to be defined.
The Bordetella virulence gene (BvgAS) two-component system, a paradigm for a
global virulence regulon, controls the expression of many "virulence factors"
expressed in the Bvg positive (Bvg+) phase that are necessary for successful
respiratory tract infection. A similarly large set of highly conserved genes are
expressed under Bvg negative (Bvg-) phase growth conditions; however, these
appear to be primarily expressed outside of the host and are thus hypothesized to
be important in an undefined extrahost reservoir. Here, we show that Bvg- phase
genes are involved in the ability of Bordetella bronchiseptica to grow and
disseminate via the complex life cycle of the amoeba Dictyostelium discoideum.
Unlike bacteria that serve as an amoeba food source, B. bronchiseptica evades
amoeba predation, survives within the amoeba for extended periods of time,
incorporates itself into the amoeba sori, and disseminates along with the amoeba.
Remarkably, B. bronchiseptica continues to be transferred with the amoeba for
months, through multiple life cycles of amoebae grown on the lawns of other
bacteria, thus demonstrating a stable relationship that allows B. bronchiseptica
to expand and disperse geographically via the D. discoideum life cycle.
Furthermore, B. bronchiseptica within the sori can efficiently infect mice,
indicating that amoebae may represent an environmental vector within which
pathogenic bordetellae expand and disseminate to encounter new mammalian hosts.
These data identify amoebae as potential environmental reservoirs as well as
amplifying and disseminating vectors for B. bronchiseptica and reveal an
important role for the Bvg- phase in these interactions.
PMID- 28403140
TI - A general approach for predicting the behavior of the Supreme Court of the United
States.
AB - Building on developments in machine learning and prior work in the science of
judicial prediction, we construct a model designed to predict the behavior of the
Supreme Court of the United States in a generalized, out-of-sample context. To do
so, we develop a time-evolving random forest classifier that leverages unique
feature engineering to predict more than 240,000 justice votes and 28,000 cases
outcomes over nearly two centuries (1816-2015). Using only data available prior
to decision, our model outperforms null (baseline) models at both the justice and
case level under both parametric and non-parametric tests. Over nearly two
centuries, we achieve 70.2% accuracy at the case outcome level and 71.9% at the
justice vote level. More recently, over the past century, we outperform an in
sample optimized null model by nearly 5%. Our performance is consistent with, and
improves on the general level of prediction demonstrated by prior work; however,
our model is distinctive because it can be applied out-of-sample to the entire
past and future of the Court, not a single term. Our results represent an
important advance for the science of quantitative legal prediction and portend a
range of other potential applications.
PMID- 28403139
TI - Increased decision thresholds enhance information gathering performance in
juvenile Obsessive-Compulsive Disorder (OCD).
AB - Patients with obsessive-compulsive disorder (OCD) can be described as cautious
and hesitant, manifesting an excessive indecisiveness that hinders efficient
decision making. However, excess caution in decision making may also lead to
better performance in specific situations where the cost of extended deliberation
is small. We compared 16 juvenile OCD patients with 16 matched healthy controls
whilst they performed a sequential information gathering task under different
external cost conditions. We found that patients with OCD outperformed healthy
controls, winning significantly more points. The groups also differed in the
number of draws required prior to committing to a decision, but not in decision
accuracy. A novel Bayesian computational model revealed that subjective sampling
costs arose as a non-linear function of sampling, closely resembling an
escalating urgency signal. Group difference in performance was best explained by
a later emergence of these subjective costs in the OCD group, also evident in an
increased decision threshold. Our findings present a novel computational model
and suggest that enhanced information gathering in OCD can be accounted for by a
higher decision threshold arising out of an altered perception of costs that, in
some specific contexts, may be advantageous.
PMID- 28403141
TI - VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers
with the plasma membrane.
AB - The cellular machinery required for the fusion of constitutive secretory vesicles
with the plasma membrane in metazoans remains poorly defined. To address this
problem we have developed a powerful, quantitative assay for measuring secretion
and used it in combination with combinatorial gene depletion studies in
Drosophila cells. This has allowed us to identify at least three SNARE complexes
mediating Golgi to PM transport (STX1, SNAP24/29 and Syb; STX1, SNAP24/29 and
YKT6; STX4, SNAP24 and Syb). RNAi mediated depletion of YKT6 and VAMP3 in
mammalian cells also blocks constitutive secretion suggesting that YKT6 has an
evolutionarily conserved role in this process. The unexpected role of YKT6 in
plasma membrane fusion may in part explain why RNAi and gene disruption studies
have failed to produce the expected phenotypes in higher eukaryotes.
PMID- 28403142
TI - Melatonin protects rats from radiotherapy-induced small intestine toxicity.
AB - Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting
toxicities following radiotherapy. Prevention of radiation enteropathy requires
protection of the small intestine. However, despite the prevalence and burden of
this pathology, there are currently no effective treatments for radiotherapy
induced gut toxicity, and this pathology remains unclear. The present study aimed
to investigate the changes induced in the rat small intestine after external
irradiation of the tongue, and to explore the potential radio-protective effects
of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues
with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5
days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin
gel or vehicle, by local application into their mouths. Our results showed that
mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3
inflammasome activation were involved in the development of radiotherapy-induced
gut toxicity. Oral treatment with melatonin gel had a protective effect in the
small intestine, which was associated with mitochondrial protection and,
consequently, with a reduced inflammatory response, blunting the NF-kappaB/NLRP3
inflammasome signaling activation. Thus, rats treated with melatonin gel showed
reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating
intestinal mucosa recovery. Our findings suggest that oral treatment with
melatonin gel may be a potential preventive therapy for radiotherapy-induced gut
toxicity in cancer patients.
PMID- 28403143
TI - A novel mechanism of cone photoreceptor adaptation.
AB - An animal's ability to survive depends on its sensory systems being able to adapt
to a wide range of environmental conditions, by maximizing the information
extracted and reducing the noise transmitted. The visual system does this by
adapting to luminance and contrast. While luminance adaptation can begin at the
retinal photoreceptors, contrast adaptation has been shown to start at later
stages in the retina. Photoreceptors adapt to changes in luminance over multiple
time scales ranging from tens of milliseconds to minutes, with the adaptive
changes arising from processes within the phototransduction cascade. Here we show
a new form of adaptation in cones that is independent of the phototransduction
process. Rather, it is mediated by voltage-gated ion channels in the cone
membrane and acts by changing the frequency response of cones such that their
responses speed up as the membrane potential modulation depth increases and slow
down as the membrane potential modulation depth decreases. This mechanism is
effectively activated by high-contrast stimuli dominated by low frequencies such
as natural stimuli. However, the more generally used Gaussian white noise stimuli
were not effective since they did not modulate the cone membrane potential to the
same extent. This new adaptive process had a time constant of less than a second.
A critical component of the underlying mechanism is the hyperpolarization
activated current, Ih, as pharmacologically blocking it prevented the long- and
mid- wavelength sensitive cone photoreceptors (L- and M-cones) from adapting.
Consistent with this, short- wavelength sensitive cone photoreceptors (S-cones)
did not show the adaptive response, and we found they also lacked a prominent Ih.
The adaptive filtering mechanism identified here improves the information flow by
removing higher-frequency noise during lower signal-to-noise ratio conditions, as
occurs when contrast levels are low. Although this new adaptive mechanism can be
driven by contrast, it is not a contrast adaptation mechanism in its strictest
sense, as will be argued in the Discussion.
PMID- 28403144
TI - Unhealthy habits persist: The ongoing presence of modifiable risk factors for
disease in women.
AB - OBJECTIVES: Vascular disease remains a leading cause of death. There are several
vascular risk factors identified that can mitigate development of disease in
ageing. We examine reported rates of modifiable risk factors in women responding
to an online health questionnaire advertised by popular media. METHODS: A sample
of 26 620 women aged over 18 was examined in 2015 with a cross-sectional health
questionnaire. The questionnaire included self-reported health, mood, lifestyle
and vascular risk factors. RESULTS: There remains high rates of modifiable risk
factors present in women. The vast majority of women (80%) reported not eating
enough fruit and vegetables. Compared to the guidelines for health, the majority
did not perform enough weekly physical activity (70%) and more than half the
participants were overweight (54%). Sufficient fruit, vegetables, fish, legumes
and physical activity were reported in less than 30% of women! CONCLUSIONS: Women
continue to report low rates of physical activity, fruit and vegetable intake and
higher BMI than recommended for good health, despite worldwide health promotion
activities aimed at changing these lifestyle factors. Programs to support healthy
living need to be reviewed and revised to reduce the burden of vascular disease
and dementia in women. Previous guidelines are not having the important impact
they should, particularly in women.
PMID- 28403146
TI - Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra
finch.
AB - Previous studies on a limited number of birds suggested that the IgD-encoding
gene was absent in birds. However, one of our recent studies showed that the gene
was definitely expressed in the ostrich and emu. Interestingly, we also
identified subclass diversification of IgM and IgY in these two birds. To better
understand immunoglobulin genes in birds, in this study, we analyzed the
immunoglobulin heavy chain genes in the zebra finch (Taeniopygia guttata) and
Gentoo penguin (Pygoscelis papua), belonging respectively to the order
Passeriformes, the most successful bird order in terms of species diversity and
numbers, and Sphenisciformes, a relatively primitive avian order. Similar to the
results obtained in chickens and ducks, only three genes encoding immunoglobulin
heavy chain isotypes, IgM, IgA and IgY, were identified in both species. Besides,
we detected a transcript encoding a short membrane-bound IgA lacking the last two
CH exons in the Gentoo penguin. We did not find any evidence supporting the
presence of IgD gene or subclass diversification of IgM/IgY in penguin or zebra
finch. The obtained data in our study provide more insights into the
immunoglobulin heavy chain genes in birds and may help to better understand the
evolution of immunoglobulin genes in tetrapods.
PMID- 28403145
TI - The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral
entry and infection.
AB - Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in
endosome maturation that emerged from a haploid genetic screen as being required
for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a
PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2
clinical trials, for its effects on entry and infection of EBOV and Marburg virus
(MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7,
Vero E6 and primary human macrophage cells, with notable potency in the
macrophages (IC50, 10 nM). We next observed that similar doses of apilimod block
EBOV-glycoprotein-virus like particle (VLP) entry and transcription-replication
competent VLP infection, suggesting that the primary mode of action of apilimod
is as an entry inhibitor, preventing release of the viral genome into the
cytoplasm to initiate replication. After providing evidence that the anti-EBOV
action of apilimod is via PIKfyve, we showed that it blocks trafficking of EBOV
VLPs to endolysosomes containing Niemann-Pick C1 (NPC1), the intracellular
receptor for EBOV. Concurrently apilimod caused VLPs to accumulate in early
endosome antigen 1-positive endosomes. We did not detect any effects of apilimod
on bulk endosome acidification, on the activity of cathepsins B and L, or on
cholesterol export from endolysosomes. Hence by antagonizing PIKfyve, apilimod
appears to block EBOV trafficking to its site of fusion and entry into the
cytoplasm. Given the drug's observed anti-filoviral activity, relatively
unexplored mechanism of entry inhibition, and reported tolerability in humans, we
propose that apilimod be further explored as part of a therapeutic regimen to
treat filoviral infections.
PMID- 28403147
TI - Cryptosporidium spp. and Giardia spp. in feces and water and the associated
exposure factors on dairy farms.
AB - The aims of this study were to verify the prevalence of Cryptosporidium spp. and
Giardia spp. in animal feces and drinking water on dairy farms and to identify a
possible relation between the exposure factors and the presence of these
parasites. Fecal samples from cattle and humans and water samples were collected
on dairy farms in Parana, Brazil. Analysis of (oo)cysts in the feces was
performed by the modified Ziehl-Neelsen staining and centrifugal flotation in
zinc sulfate. Test-positive samples were subjected to nested PCR amplification of
the 18SSU ribosomal RNA gene for identification of Cryptosporidium and Giardia
and of the gp60 gene for subtyping of Cryptosporidium. Microbiological analysis
of water was carried out by the multiple-tube method and by means of a
chromogenic substrate, and parasitological analysis was performed on 31 samples
by direct immunofluorescence and nested PCR of the genes mentioned above.
Identification of the species of Cryptosporidium was performed by sequencing and
PCR with analysis of restriction fragment length polymorphisms. The prevalence of
Giardia and Cryptosporidium was higher in calves than in adults. Among the
samples of cattle feces, Cryptosporidium parvum was identified in 41 (64%), C.
ryanae in eight (12.5%), C. bovis in four (6.3%), C. andersoni in five (7.8%),
and a mixed infection in 20 samples (31.3%). These parasites were not identified
in the samples of human feces. Thermotolerant coliform bacteria were identified
in 25 samples of water (45.5%). Giardia duodenalis and C. parvum were identified
in three water samples. The gp60 gene analysis of C. parvum isolates revealed the
presence of two strains (IIaA20G1R1 and IIaA17G2R2) in the fecal samples and one
(IIaA17G2R1) in the water samples. The presence of coliforms was associated with
the water source, structure and degradation of springs, rain, and turbidity. The
prevalence of protozoa was higher in calves up to six months of age. C. parvum
and G. duodenalis were identified in the water of dairy farms, as were
thermotolerant coliforms; these findings point to the need for guidance on
handling of animals, preservation of water sources, and water treatment.
PMID- 28403148
TI - Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and
hepatocyte apoptosis.
AB - BACKGROUND AND AIMS: Neutrophil infiltration of the liver is a typical feature of
alcoholic liver injury. Human neutrophil peptide (HNP)-1 is an antimicrobial
peptide secreted by neutrophils. The aim of this study was to determine if HNP-1
affects ethanol-induced liver injury and to examine the mechanism of liver injury
induced by HNP-1. METHODS: Transgenic (TG) mice expressing HNP-1 under the
control of a beta-actin-based promoter were established. Ethanol was orally
administered to HNP-1 TG or wild-type C57BL/6N (WT) mice. SK-Hep1 hepatocellular
carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in
vitro. RESULTS: After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte
apoptosis were significantly more severe in TG mice than in WT mice. Levels of
CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice.
Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and
cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1,
phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG
mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver
was significantly lower in TG mice than in WT mice. Analysis of microRNAs in
liver tissue showed that miR-34a-5p expression was significantly higher in TG
mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased
the apoptosis with the decreased level of Bcl2 in a concentration-dependent
manner in vitro. CONCLUSIONS: HNP-1 secreted by neutrophils may exacerbate
alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2
expression and an increase in miR-34a-5p expression.
PMID- 28403149
TI - A protocol for identifying suitable biomarkers to assess fish health: A
systematic review.
AB - BACKGROUND: Biomarkers have been used extensively to provide the connection
between external levels of contaminant exposure, internal levels of tissue
contamination, and early adverse effects in organisms. OBJECTIVES: To present a
three-step protocol for identifying suitable biomarkers to assess fish health in
coastal and marine ecosystems, using Gladstone Harbour (Australia) as a case
study. METHODS: Prior to applying our protocol, clear working definitions for
biomarkers were developed to ensure consistency with the global literature on
fish health assessment. First, contaminants of concern were identified based on
the presence of point and diffuse sources of pollution and available monitoring
data for the ecosystem of interest. Second, suitable fish species were identified
using fisheries dependent and independent data, and prioritised based on
potential pathways of exposure to the contaminants of concern. Finally, a
systematic and critical literature review was conducted on the use of biomarkers
to assess the health of fish exposed to the contaminants of concern.
RESULTS/DISCUSSION: We present clear working definitions for bioaccumulation
markers, biomarkers of exposure, biomarkers of effect and biomarkers of
susceptibility. Based on emission and concentration information, seven metals
were identified as contaminants of concern for Gladstone Harbour. Twenty out of
232 fish species were abundant enough to be potentially suitable for biomarker
studies; five of these were prioritised based on potential pathways of exposure
and susceptibility to metals. The literature search on biomarkers yielded 5,035
articles, of which 151met the inclusion criteria. Based on our review, the most
suitable biomarkers include bioaccumulation markers, biomarkers of exposure
(CYP1A, EROD, SOD, LPOX, HSP, MT, DNA strand breaks, micronuclei, apoptosis), and
biomarkers of effect (histopathology, TAG:ST). CONCLUSION: Our protocol outlines
a clear pathway to identify suitable biomarkers to assess fish health in coastal
and marine ecosystems, which can be applied to biomarker studies in aquatic
ecosystems around the world.
PMID- 28403150
TI - PEDF increases the tumoricidal activity of macrophages towards prostate cancer
cells in vitro.
AB - BACKGROUND: Although inflammation and prostate cancer (PCa) have been linked, the
molecular interactions between macrophages and PCa cells are poorly explored.
Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor
factor. We previously showed that PEDF induces macrophages recruitment in vitro,
correlates with macrophages density in human prostate, and stimulates macrophages
polarization towards the classically activated pathway. Here, we demonstrate that
PEDF modulates the interaction between macrophages and PCa cells through a
bidirectional signalling leading to tumor cell apoptosis and phagocytosis.
METHODS: RAW 264.7 and THP-1 cells, and BMDMs were grown in vitro as mono- or co
cultures with PC3 or CL1 tumor cells. The effects of PEDF and its derived P18
peptide were measured on macrophages differentiation, migration, and superoxide
production, and tumor cell apoptosis and phagocytosis. PEDF receptors (ATP5B,
PNPLA2, and LRP6) and CD47 mRNA and protein expression were quantified in
macrophages and tumor cells by quantitative RT-PCR, western blot,
immunofluorescence and flow cytometry. RESULTS: We found that PEDF induced the
migration of macrophages towards tumor 3D spheroids and 2D cultures. In co
culture, PEDF increased PCa cells phagocytosis through an indirect apoptosis
dependent mechanism. Moreover, PEDF stimulated the production of superoxide by
macrophages. Conditioned media from macrophages exposed to PEDF induced tumor
cells apoptosis in contrast to control conditioned media suggesting that ROS may
be involved in tumor cells apoptosis. ATP5B and PNPLA2 PEDF receptors on
macrophages and CD47 on tumor cells were respectively up- and down-regulated by
PEDF. As PEDF, blocking CD47 induced phagocytosis. Inhibiting ATP5B reduced
phagocytosis. Inversely, PNPLA2 inhibition blocks differentiation but maintains
phagocytosis. CD47-induced phagocytosis was partially reverted by ATP5B
inhibition suggesting a complementary action. Similar effects were observed with
P18 PEDF-derived peptide. CONCLUSIONS: These data established that modulating the
molecular interactions between macrophages and PCa cells using PEDF may be a
promising strategy for PCa treatment.
PMID- 28403151
TI - Physical Activity on Prescription (PAP), in patients with metabolic risk factors.
A 6-month follow-up study in primary health care.
AB - There is strong evidence that inadequate physical activity (PA) leads to an
increased risk of lifestyle-related diseases and premature mortality. Physical
activity on prescription (PAP) is a method to increase the level of PA of
patients in primary care, but needs further evaluation. The aim of this
observational study was to explore the association between PAP-treatment and the
PA level of patients with metabolic risk factors and the relationship between
changes in the PA level and health outcomes at the 6 month follow-up. This study
included 444 patients in primary care, aged 27-85 years (56% females), who were
physically inactive with at least one component of metabolic syndrome. The PAP
treatment model included: individualized dialogue concerning PA, prescribed PA,
and a structured follow-up. A total of 368 patients (83%) completed the 6 months
of follow-up. Of these patients, 73% increased their PA level and 42% moved from
an inadequate PA level to sufficient, according to public health recommendations.
There were significant improvements (p<= 0.05) in the following metabolic risk
factors: body mass index, waist circumference, systolic blood pressure, fasting
plasma glucose, cholesterol, and low density lipoprotein. There were also
significant improvements regarding health-related quality of life, assessed by
the Short Form 36, in: general health, vitality, social function, mental health,
role limitation-physical/emotional, mental component summary, and physical
component summary. Regression analysis showed a significant association between
changes in the PA level and health outcomes. During the first 6-month period, the
caregiver provided PAP support 1-2 times. This study indicates that an individual
based model of PAP-treatment has the potential to change people's PA behavior
with improved metabolic risk factors and self-reported quality of life at the 6
month follow-up. Thus, PAP seems to be feasible in a clinical primary care
practice, with minimum effort from healthcare professionals.
PMID- 28403152
TI - Linking phenological events in migratory passerines with a changing climate: 50
years in the Laurel Highlands of Pennsylvania.
AB - Advanced timing of both seasonal migration and reproduction in birds has been
strongly associated with a warming climate for many bird species. Phenological
responses to climate linking these stages may ultimately impact fitness. We
analyzed five decades of banding data from 17 migratory bird species to
investigate 1) how spring arrival related to timing of breeding, 2) if the
interval between arrival and breeding has changed with increasing spring
temperatures, and 3) whether arrival timing or breeding timing best predicted
local productivity. Four of 17 species, all mid- to long-distance migrants,
hatched young earlier in years when migrants arrived earlier to the breeding
grounds (~1:1 day advancement). The interval between arrival on breeding grounds
and appearance of juveniles shortened with warmer spring temperatures for 12
species (1-6 days for every 1 degrees C increase) and over time for seven species
(1-8 days per decade), suggesting that some migratory passerines adapt to climate
change by laying more quickly after arrival or reducing the time from laying to
fledging. We found more support for the former, that the rate of reproductive
advancement was higher than that for arrival in warm years. Timing of spring
arrival and breeding were both poor predictors of avian productivity for most
migrants analyzed. Nevertheless, we found evidence that fitness benefits may
occur from shifts to earlier spring arrival for the multi-brooded Song Sparrow.
Our results uniquely demonstrate that co-occurring avian species are
phenologically plastic in their response to climate change on their breeding
grounds. If migrants continue to show a weaker response to temperatures during
migration than breeding, and the window between arrival and optimal breeding
shortens further, biological constraints to plasticity may limit the ability of
species to adapt successfully to future warming.
PMID- 28403153
TI - Epidemiological analysis of Leishmania tropica strains and giemsa-stained smears
from Syrian and Turkish leishmaniasis patients using multilocus microsatellite
typing (MLMT).
AB - Turkey is located in an important geographical location, in terms of the
epidemiology of vector-borne diseases, linking Asia and Europe. Cutaneous
leishmaniasis (CL) is one of the endemic diseases in a Turkey and according to
the Ministry Health of Turkey, 45% of CL patients originate from Sanliurfa
province located in southeastern Turkey. Herein, the epidemiological status of
CL, caused by L. tropica, in Turkey was examined using multilocus microsatellite
typing (MLMT) of strains obtained from Turkish and Syrian patients. A total of 38
cryopreserved strains and 20 Giemsa-stained smears were included in the present
study. MLMT was performed using 12 highly specific microsatellite markers. Delta
K (DeltaK) calculation and Bayesian statistics were used to determine the
population structure. Three main populations (POP A, B and C) were identified and
further examination revealed the presence of three subpopulations for POP B and
C. Combined analysis was performed using the data of previously typed L. tropica
strains and Mediterranean and Sanliurfa populations were identified. This finding
suggests that the epidemiological status of L. tropica is more complicated than
expected when compared to previous studies. A new population, comprised of Syrian
L. tropica samples, was reported for the first time in Turkey, and the data
presented here will provide new epidemiological information for further studies.
PMID- 28403154
TI - Effect of transdermal magnesium cream on serum and urinary magnesium levels in
humans: A pilot study.
AB - BACKGROUND: Oral magnesium supplementation is commonly used to support a low
magnesium diet. This investigation set out to determine whether magnesium in a
cream could be absorbed transdermally in humans to improve magnesium status.
METHODS AND FINDINGS: In this single blind, parallel designed pilot study, n = 25
participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) were
randomly assigned to either a 56mg/day magnesium cream or placebo cream group for
two weeks. Magnesium serum and 24hour urinary excretion were measured at baseline
and at 14 days intervention. Food diaries were recorded for 8 days during this
period. Mg test and placebo groups' serum and urinary Mg did not differ at
baseline. After the Mg2+ cream intervention there was a clinically relevant
increase in serum magnesium (0.82 to 0.89 mmol/l,p = 0.29) that was not seen in
the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant
(p = 0.02)) in a subgroup of non-athletes. Magnesium urinary excretion increased
from baseline slightly in the Mg2+ group but with no statistical significance (p
= 0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1%
increase in urinary Mg2+ while these figures for the placebo group were smaller,
i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both
serum and urine concentrations showed no statistically significant change after
the application of the placebo cream. CONCLUSION: No previous studies have looked
at transdermal absorbency of Mg2+ in human subjects. In this pilot study,
transdermal delivery of 56 mg Mg/day (a low dose compared with commercial
transdermal Mg2+ products available) showed a larger percentage rise in both
serum and urinary markers from pre to post intervention compared with subjects
using the placebo cream, but statistical significance was achieved only for serum
Mg2+ in a subgroup of non-athletes. Future studies should look at higher dosage
of magnesium cream for longer durations. TRIAL REGISTRATION: ISRCTN registry ID
No. ISRTN15136969.
PMID- 28403155
TI - Fruit consumption and physical activity in relation to all-cause and
cardiovascular mortality among 70,000 Chinese adults with pre-existing vascular
disease.
AB - OBJECTIVES: To assess the associations of fresh fruit consumption and total
physical activity with all-cause and cardiovascular mortality among Chinese
adults who have been diagnosed with cardiovascular disease (CVD) or hypertension.
METHODS: During 2004-08, the China Kadoorie Biobank study recruited 70,047
adults, aged 30-79 years, with physician-diagnosed stroke or transient ischaemic
attack, ischemic heart disease, or hypertension. Information on diet and physical
activity was collected using an interviewer-administered electronic
questionnaire. Cox regression was used to yield hazard ratios (HRs) for the
independent and joint associations of fresh fruit consumption and total physical
activity with mortality. RESULTS: At baseline, 32.9% of participants consumed
fresh fruit regularly (i.e. >3 days/week) and the mean total physical activity
were 15.8 (SD = 11.8) MET-hr/day. During ~7-years follow-up, 6569 deaths occurred
with 3563 from CVD. Compared to participants with <1 day/week fruit consumption,
regular consumers had HR (95% CI) of 0.84 (0.79-0.89) for all-cause mortality and
0.79 (0.73-0.86) for CVD mortality. The HRs for the top vs bottom tertile of
physical activity were 0.68 (0.64-0.72) and 0.65 (0.60-0.71), respectively, with
no clear evidence of reverse causality. After correcting for regression dilution,
each 100 g/day usual consumption of fresh fruit or 10 MET-hr/day usual levels of
physical activity was associated with 23-29% lower mortality. The combination of
regular fruit consumption with top 3rd of physical activity (>16.53 MET-hr/day)
was associated with about 40% lower mortality. CONCLUSION: Among Chinese adults
with pre-existing vascular disease, higher physical activity and fruit
consumption were both independently and jointly associated with lower mortality.
PMID- 28403156
TI - Direct fluorescence detection of VirE2 secretion by Agrobacterium tumefaciens.
AB - VirE2 is a ssDNA binding protein essential for virulence in Agrobacterium
tumefaciens. A tetracysteine mutant (VirE2-TC) was prepared for in vitro and in
vivo fluorescence imaging based on the ReAsH reagent. VirE2-TC was found to be
biochemically active as it binds both ssDNA and the acidic secretion chaperone
VirE1. It was also biologically functional in complementing virE2 null strains
transforming Arabidopsis thaliana roots and Nicotiana tabacum leaves. In vitro
experiments demonstrated a two-color fluorescent complex using VirE2-TC/ReAsH and
Alexa Fluor 488 labeled ssDNA. In vivo, fluorescent VirE2-TC/ReAsH was detected
in bacteria and in plant cells at time frames relevant to transformation.
PMID- 28403158
TI - What can we learn from corporate sustainability reporting? Deriving propositions
for research and practice from over 9,500 corporate sustainability reports
published between 1999 and 2015 using topic modelling technique.
AB - Organizations are increasingly using sustainability reports to inform their
stakeholders and the public about their sustainability practices. We apply topic
modelling to 9,514 sustainability reports published between 1999 and 2015 in
order to identify common topics and, thus, the most common practices described in
these reports. In particular, we identify forty-two topics that reflect
sustainability and focus on the coverage and trends of economic, environmental,
and social sustainability topics. Among the first to analyse such a large amount
of data on organizations' sustainability reporting, the paper serves as an
example of how to apply natural language processing as a strategy of inquiry in
sustainability research. The paper also derives from the data analysis ten
propositions for future research and practice that are of immediate value for
organizations and researchers.
PMID- 28403157
TI - Effects of age and nutritional state on the expression of gustatory receptors in
the honeybee (Apis mellifera).
AB - Gustatory receptors (Grs) expressed in insect taste neurons signal the presence
of carbohydrates, sugar alcohols, CO2, bitter compounds and oviposition
stimulants. The honeybee (Apis mellifera) has one of the smallest Gr gene sets
(12 Gr genes) of any insect whose genome has been sequenced. Honeybees live in
eusocial colonies with a division of labour and perform age-dependent behavioural
tasks, primarily food collection. Here, we used RT-qPCR to quantify Gr mRNA in
honeybees at two ages (newly-emerged and foraging-age adults) to examine the
relationship between age-related physiology and expression of Gr genes. We
measured the Gr mRNAs in the taste organs and also the brain and gut. The mRNA of
all Gr genes was detected in all tissues analysed but showed plasticity in
relative expression across tissues and in relation to age. Overall, Gr gene
expression was higher in the taste organs than in the internal tissues but did
not show an overall age-dependent difference. In contrast Gr gene expression in
brain was generally higher in foragers, which may indicate greater reliance on
internal nutrient sensing. Expression of the candidate sugar receptors AmGr1,
AmGr2 and AmGr3 in forager brain was affected by the types of sugars bees fed on.
The levels of expression in the brain were greater for AmGr1 but lower for AmGr2
and AmGr3 when bees were fed with glucose and fructose compared with sucrose.
Additionally, AmGr3 mRNA was increased in starved bees compared to bees provided
ad libitum sucrose. Thus, expression of these Grs in forager brain reflects both
the satiety state of the bee (AmGr3) and the type of sugar on which the bee has
fed.
PMID- 28403159
TI - Improved supervised classification of accelerometry data to distinguish behaviors
of soaring birds.
AB - Soaring birds can balance the energetic costs of movement by switching between
flapping, soaring and gliding flight. Accelerometers can allow quantification of
flight behavior and thus a context to interpret these energetic costs. However,
models to interpret accelerometry data are still being developed, rarely trained
with supervised datasets, and difficult to apply. We collected accelerometry data
at 140Hz from a trained golden eagle (Aquila chrysaetos) whose flight we recorded
with video that we used to characterize behavior. We applied two forms of
supervised classifications, random forest (RF) models and K-nearest neighbor
(KNN) models. The KNN model was substantially easier to implement than the RF
approach but both were highly accurate in classifying basic behaviors such as
flapping (85.5% and 83.6% accurate, respectively), soaring (92.8% and 87.6%) and
sitting (84.1% and 88.9%) with overall accuracies of 86.6% and 92.3%
respectively. More detailed classification schemes, with specific behaviors such
as banking and straight flights were well classified only by the KNN model
(91.24% accurate; RF = 61.64% accurate). The RF model maintained its accuracy of
classifying basic behavior classification accuracy of basic behaviors at sampling
frequencies as low as 10Hz, the KNN at sampling frequencies as low as 20Hz.
Classification of accelerometer data collected from free ranging birds
demonstrated a strong dependence of predicted behavior on the type of
classification model used. Our analyses demonstrate the consequence of different
approaches to classification of accelerometry data, the potential to optimize
classification algorithms with validated flight behaviors to improve
classification accuracy, ideal sampling frequencies for different classification
algorithms, and a number of ways to improve commonly used analytical techniques
and best practices for classification of accelerometry data.
PMID- 28403160
TI - Determinants of diabetic nephropathy in Ayder Referral Hospital, Northern
Ethiopia: A case-control study.
AB - BACKGROUND: Diabetic nephropathy is the most serious complication of diabetes
which leads to end-stage renal failure and other complication of diabetes
mellitus. Determinants of Diabetic nephropathy are not consistent in different
studies and associated factors to chronic complications of diabetes are not
specific and there are limited studies specific to diabetic nephropathy. Thus,
the aim of this study is to identify determinants of diabetic nephropathy in
Ayder Referral Hospital, Northern Ethiopia. METHODS: A case-control study was
conducted from February 14 to May 8 2016. Diabetic patients who developed
nephropathy in the last two years were the cases and diabetic patients free of
nephropathy were controls. Cases and controls were identified detailed review of
the chronic care follow up chart. Then simple random sampling was used to select
sample of 420 (with control to case ratio of 4:1) resulting in 84 cases and 336
controls. Record review and interviewer administered questionnaire were used to
collect data. Data was coded and entered in to Epi-Data version 3.1 and then
exported to STATA 12 for analysis. Variables with P-values< 0.25 in Bivariate
logistic regression were selected for multiple logistic regressions to determine
independent determinants of diabetic nephropathy. OR was calculated with 95% CI
to show strength of association. RESULT: The mean age (+/-Standard deviation) for
the cases and the controls were 52(SD: +/-1.34) and 42.4(SD: +/-0.8)
respectively. In multiple logistic regressions age of patient (AOR: 1.037 95%CI:
1.01-1.064), duration of diabetes after diagnosis (AOR for one year increase:
1.09 95%CI: 1.036-1.15), not-adhered to blood glucose measurement at home (AOR:
6.81 95%CI: 1.15-40.24), having Systolic Hypertension (AOR;2.13 (1.002-4.51),
poor glycemic control (AOR;2.71 95%CI: (1.49-4.95), being overweight(AOR;2.7(1.47
4.96) were the independent predictors of diabetic nephropathy. CONCLUSION: In the
light of these findings, targeted interventions should be designed at the follow
up clinic to address the risk of developing diabetic nephropathy among the risk
groups.
PMID- 28403161
TI - Age-related effects of body mass on fertility and litter size in roe deer.
AB - We analysed effects of females' body mass and age on reproductive capacity of
European roe deer (Capreolus capreolus) in a large sample set of 1312 females
(305 yearlings and 1007 adults), hunted throughout Slovenia, central Europe, in
the period 2013-2015. Body mass positively affected probability of ovulation and
potential litter size (number of corpora lutea), although its effect was more
pronounced in yearlings than in adults. Between age groups, we found clear
differences in responses of both reproductive parameters to body mass which
influences primarily reproductive performance of younger, and in particular,
lighter individuals: at the same body mass yearlings would at average have
smaller litters than adults, and at lower body mass also young to middle-aged
adults would have smaller litters than old ones. In addition, while yearlings
have to reach a critical threshold body mass to attain reproductive maturity,
adult females are fertile (produce ova) even at low body mass. However, at higher
body mass also younger individuals shift their efforts into the reproduction, and
after reaching an age-specific threshold the body mass does not have any further
effects on the reproductive output of roe deer females. Increased reproductive
capacity at more advanced age, combined with declining body mass suggests that
old does allocate more of their resources in reproduction than in body condition.
PMID- 28403162
TI - Maintaining extensivity in evolutionary multiplex networks.
AB - In this paper, we explore the role of network topology on maintaining the
extensive property of entropy. We study analytically and numerically how the
topology contributes to maintaining extensivity of entropy in multiplex networks,
i.e. networks of subnetworks (layers), by means of the sum of the positive
Lyapunov exponents, HKS, a quantity related to entropy. We show that extensivity
relies not only on the interplay between the coupling strengths of the dynamics
associated to the intra (short-range) and inter (long-range) interactions, but
also on the sum of the intra-degrees of the nodes of the layers. For the
analytically treated networks of size N, among several other results, we show
that if the sum of the intra-degrees (and the sum of inter-degrees) scales as
Ntheta+1, theta > 0, extensivity can be maintained if the intra-coupling (and the
inter-coupling) strength scales as N-theta, when evolution is driven by the
maximisation of HKS. We then verify our analytical results by performing
numerical simulations in multiplex networks formed by electrically and chemically
coupled neurons.
PMID- 28403163
TI - Impact of human monocyte and macrophage polarization on NLR expression and NLRP3
inflammasome activation.
AB - Inflammasomes are multiprotein complexes nucleating around an NLR (Nucleotide
binding domain and Leucine-rich Repeat containing protein), which regulate the
secretion of the pro-inflammatory interleukin (IL)-1beta and IL-18 cytokines.
Monocytes and macrophages, the main cells expressing the inflammasome genes,
adapt to their surrounding microenvironment by a phenotypic polarization towards
a pro-inflammatory M1 phenotype that promotes inflammation or an anti
inflammatory M2 phenotype important for resolution of inflammation. Despite the
importance of inflammasomes in health and disease, little is known about
inflammasome gene expression in relevant human cells and the impact of monocyte
and macrophage polarization in inflammasome gene expression. We examined the
expression of several members of the NLR, caspase and cytokine family, and we
studied the activation of the well-described NLRP3 inflammasome in an
experimental model of polarized human primary monocytes and monocyte-derived
macrophages (M1/M2 phenotypes) before and after activation with LPS, a well
characterized microbial pattern used in inflammasome activation studies. Our
results show that the differentiation of monocytes to macrophages alters NLR
expression. Polarization using IFN-gamma (M1 phenotype), induces among the NLRs
studied, only the expression of NOD2. One of the key results of our study is that
the induction of NLRP3 expression by LPS is inhibited in the presence of IL-4+IL
13 (M2 phenotype) at both mRNA and protein level in monocytes and macrophages.
Unlike caspase-3, the expression of inflammasome-related CASP1 (encodes caspase
1) and CASP4 (encodes caspase-4) is up-regulated in M1 but not in M2 cells.
Interestingly, the presence of LPS marginally influenced IL18 mRNA expression and
secretion, unlike its impact on IL1B. Our data provide the basis for a better
understanding of the role of different inflammasomes within a given environment
(M1 and M2) in human cells and their impact in the pathophysiology of several
important inflammatory disorders.
PMID- 28403164
TI - Characterising the latent structure and organisation of self-reported thoughts,
feelings and behaviours in adolescents and young adults.
AB - Little is known about the underlying relationships between self-reported mental
health items measuring both positive and negative emotional and behavioural
symptoms at the population level in young people. Improved measurement of the
full range of mental well-being and mental illness may aid in understanding the
aetiological substrates underlying the development of both mental wellness as
well as specific psychiatric diagnoses. A general population sample aged 14 to 24
years completed self-report questionnaires on anxiety, depression, psychotic-like
symptoms, obsessionality and well-being. Exploratory and confirmatory factor
models for categorical data and latent profile analyses were used to evaluate the
structure of both mental wellness and illness items. First order, second order
and bifactor structures were evaluated on 118 self-reported items obtained from
2228 participants. A bifactor solution was the best fitting latent variable model
with one general latent factor termed 'distress' and five 'distress independent'
specific factors defined as self-confidence, antisocial behaviour, worry,
aberrant thinking, and mood. Next, six distinct subgroups were derived from a
person-centred latent profile analysis of the factor scores. Finally, concurrent
validity was assessed using information on hazardous behaviours (alcohol use,
substance misuse, self-harm) and treatment for mental ill health: both
discriminated between the latent traits and latent profile subgroups. The
findings suggest a complex, multidimensional mental health structure in the youth
population rather than the previously assumed first or second order factor
structure. Additionally, the analysis revealed a low hazardous behaviour/low
mental illness risk subgroup not previously described. Population sub-groups show
greater validity over single variable factors in revealing mental illness risks.
In conclusion, our findings indicate that the structure of self reported mental
health is multidimensional in nature and uniquely finds improved prediction to
mental illness risk within person-centred subgroups derived from the
multidimensional latent traits.
PMID- 28403165
TI - Triploid atlantic salmon (Salmo salar L.) post-smolts accumulate prevalence more
slowly than diploid salmon following bath challenge with salmonid alphavirus
subtype 3.
AB - Triploid Atlantic salmon (Salmo salar L.) may play an important role in the
sustainable expansion of the Norwegian aquaculture industry. Therefore, the
susceptibility of triploid salmon to common infections such as salmonid
alphavirus (SAV), the causative agent of pancreas disease (PD), requires
investigation. In this study, shortly after seawater transfer, diploid and
triploid post-smolts were exposed to SAV type 3 (SAV3) using a bath challenge
model where the infectious dose was 48 TCID50 ml-1 of tank water. Copy number
analysis of SAV3 RNA in heart tissue showed that there was no difference in viral
loads between the diploids and triploids. Prevalence reached 100% by the end of
the 35-day experimental period in both infected groups. However, prevalence
accumulated more slowly in the triploid group reaching 19% and 56% at 14 and 21
days post exposure (dpe) respectively. Whereas prevalence in the diploid group
was 82% and 100% at the same time points indicating some differences between
diploid and triploid fish. Both heart and pancreas from infected groups at 14 dpe
showed typical histopathological changes associated with pancreas disease.
Observation of this slower accumulation of prevalence following a natural
infection route was possible due to the early sampling points and the exposure to
a relatively low dose of virus. The triploid salmon in this study were not more
susceptible to SAV3 than diploid salmon indicating that they could be used
commercially to reduce the environmental impact of escaped farmed fish
interbreeding with wild salmon. This is important information regarding the
future use of triploid fish in large scale aquaculture where SAV3 is a financial
threat to increased production.
PMID- 28403166
TI - Functional decay in tree community within tropical fragmented landscapes: Effects
of landscape-scale forest cover.
AB - As tropical rainforests are cleared, forest remnants are increasingly isolated
within agricultural landscapes. Understanding how forest loss impacts on species
diversity can, therefore, contribute to identifying the minimum amount of habitat
required for biodiversity maintenance in human-modified landscapes. Here, we
evaluate how the amount of forest cover, at the landscape scale, affects patterns
of species richness, abundance, key functional traits and common taxonomic
families of adult trees in twenty Brazilian Atlantic rainforest landscapes. We
found that as forest cover decreases, both tree community richness and abundance
decline, without exhibiting a threshold. At the family-level, species richness
and abundance of the Myrtaceae and Sapotaceae were also negatively impacted by
the percent forest remaining at the landscape scale. For functional traits, we
found a reduction in shade-tolerant, animal-dispersed and small-seeded species
following a decrease in the amount of forest retained in landscapes. These
results suggest that the amount of forest in a landscape is driving non-random
losses in phylogenetic and functional tree diversity in Brazil's remaining
Atlantic rainforests. Our study highlights potential restraints on the
conservation value of Atlantic rainforest remnants in deforested landscapes in
the future.
PMID- 28403167
TI - Wireless multihop backhauls for rural areas: A preliminary study.
AB - Rural areas have very low revenue potential. The major issue in providing low
cost broadband to rural areas is to provide reliable backhaul connections that
spread over tens or even hundreds of miles, connecting villages to the nearest
service provider. Along with aerial networks of Google and Facebook, there has
been a considerable amount of research toward long-distance terrestrial WiFi
links. As a comparison, WiFi routers are easier to be deployed and maintained by
non-technical people from the local communities, whereas the aerial networks
require professional support to operate. Moreover, they are still in the
experimentation phase. However, the long distance WiFi links require high-gain
directional antennas and very expensive tall towers for high data rates. On the
other hand, multihop paths with stronger links may provide better data rates
without the need of tall towers. In this paper, we evaluated the concept of using
such multihop WiFi links for long backhaul connections. Our simulation results
show that these networks can possibly be a cost-effective and practical solution
for rural connectivity. These initial results can serve as a first step to
understand the comprehensive feasibility of using multihop WiFi networks for
backhaul connections in rural area.
PMID- 28403168
TI - From body scale ontogeny to species ontogeny: Histological and morphological
assessment of the Late Devonian acanthodian Triazeugacanthus affinis from
Miguasha, Canada.
AB - Growth series of Palaeozoic fishes are rare because of the fragility of larval
and juvenile specimens owing to their weak mineralisation and the scarcity of
articulated specimens. This rarity makes it difficult to describe early
vertebrate growth patterns and processes in extinct taxa. Indeed, only a few
growth series of complete Palaeozoic fishes are available; however, they allow
the growth of isolated elements to be described and individual growth from these
isolated elements to be inferred. In addition, isolated and in situ scales are
generally abundant and well-preserved, and bring information on (1) their
morphology and structure relevant to phylogenetic relationships and (2)
individual growth patterns and processes relative to species ontogeny. The Late
Devonian acanthodian Triazeugacanthus affinis from the Miguasha Fossil
Lagerstatte preserves one of the best known fossilised ontogenies of early
vertebrates because of the exceptional preservation, the large size range, and
the abundance of complete specimens. Here, we present morphological,
histological, and chemical data on scales from juvenile and adult specimens
(scales not being formed in larvae). Histologically, Triazeugacanthus scales are
composed of a basal layer of acellular bone housing Sharpey's fibers, a mid-layer
of mesodentine, and a superficial layer of ganoine. Developmentally, scales grow
first through concentric addition of mesodentine and bone around a central
primordium and then through superposition of ganoine layers. Ontogenetically,
scales form first in the region below the dorsal fin spine, then squamation
spreads anteriorly and posteriorly, and on fin webs. Phylogenetically,
Triazeugacanthus scales show similarities with acanthodians (e.g. "box-in-box"
growth), chondrichthyans (e.g. squamation pattern), and actinopterygians (e.g.
ganoine). Scale histology and growth are interpreted in the light of a new
phylogenetic analysis of gnathostomes supporting acanthodians as stem
chondrichthyans.
PMID- 28403170
TI - Are fundamental niches larger than the realized? Testing a 50-year-old prediction
by Hutchinson.
AB - For more than 50 years ecological niches have been defined as combinations of
multidimensional environmental conditions permitting a species to survive and
reproduce. A fundamental niche (NF) is defined as the set of conditions within
which a species can live in the absence of competitors, and a realized niche (NR)
is a NF hypothetically reduced by competitive interactions (and some other
limiting factors). This definition implies that NF is "larger" than NR, something
that has been nearly universally accepted by ecologists. However, there have been
few attempts at empirical tests. Here, we present a novel quantitative test using
one-dimensional estimates of NF for 105 species of reptiles and amphibians, and
estimates of NR obtained from ~1.4 x 104 field observations. To specify our test,
we operationalize the original classification of niche types. Our results
predominantly support the hypothesis that NF 'is larger' than NR and we highlight
the theoretical and practical importance of quantifying niches.
PMID- 28403169
TI - Osteopontin activates the diabetes-associated potassium channel TALK-1 in
pancreatic beta-cells.
AB - Glucose-stimulated insulin secretion (GSIS) relies on beta-cell Ca2+ influx,
which is modulated by the two-pore-domain K+ (K2P) channel, TALK-1. A gain-of
function polymorphism in KCNK16, the gene encoding TALK-1, increases risk for
developing type-2 diabetes. While TALK-1 serves an important role in modulating
GSIS, the regulatory mechanism(s) that control beta-cell TALK-1 channels are
unknown. Therefore, we employed a membrane-specific yeast two-hybrid (MYTH) assay
to identify TALK-1-interacting proteins in human islets, which will assist in
determining signaling modalities that modulate TALK-1 function. Twenty-one
proteins from a human islet cDNA library interacted with TALK-1. Some of these
interactions increased TALK-1 activity, including intracellular osteopontin
(iOPN). Intracellular OPN is highly expressed in beta-cells and is upregulated
under pre-diabetic conditions to help maintain normal beta-cell function;
however, the functional role of iOPN in beta-cells is poorly understood. We found
that iOPN colocalized with TALK-1 in pancreatic sections and coimmunoprecipitated
with human islet TALK-1 channels. As human beta-cells express two K+ channel
forming variants of TALK-1, regulation of these TALK-1 variants by iOPN was
assessed. At physiological voltages iOPN activated TALK-1 transcript variant 3
channels but not TALK-1 transcript variant 2 channels. Activation of TALK-1
channels by iOPN also hyperpolarized resting membrane potential (Vm) in HEK293
cells and in primary mouse beta-cells. Intracellular OPN was also knocked down in
beta-cells to test its effect on beta-cell TALK-1 channel activity. Reducing beta
cell iOPN significantly decreased TALK-1 K+ currents and increased glucose
stimulated Ca2+ influx. Importantly, iOPN did not affect the function of other
K2P channels or alter Ca2+ influx into TALK-1 deficient beta-cells. These results
reveal the first protein interactions with the TALK-1 channel and found that an
interaction with iOPN increased beta-cell TALK-1 K+ currents. The TALK-1/iOPN
complex caused Vm hyperpolarization and reduced beta-cell glucose-stimulated Ca2+
influx, which is predicted to inhibit GSIS.
PMID- 28403171
TI - Bacterial biofilm under flow: First a physical struggle to stay, then a matter of
breathing.
AB - Bacterial communities attached to surfaces under fluid flow represent a
widespread lifestyle of the microbial world. Through shear stress generation and
molecular transport regulation, hydrodynamics conveys effects that are very
different by nature but strongly coupled. To decipher the influence of these
levers on bacterial biofilms immersed in moving fluids, we quantitatively and
simultaneously investigated physicochemical and biological properties of the
biofilm. We designed a millifluidic setup allowing to control hydrodynamic
conditions and to monitor biofilm development in real time using microscope
imaging. We also conducted a transcriptomic analysis to detect a potential
physiological response to hydrodynamics. We discovered that a threshold value of
shear stress determined biofilm settlement, with sub-piconewton forces sufficient
to prevent biofilm initiation. As a consequence, distinct hydrodynamic
conditions, which set spatial distribution of shear stress, promoted distinct
colonization patterns with consequences on the growth mode. However, no direct
impact of mechanical forces on biofilm growth rate was observed. Consistently, no
mechanosensing gene emerged from our differential transcriptomic analysis
comparing distinct hydrodynamic conditions. Instead, we found that hydrodynamic
molecular transport crucially impacts biofilm growth by controlling oxygen
availability. Our results shed light on biofilm response to hydrodynamics and
open new avenues to achieve informed design of fluidic setups for investigating,
engineering or fighting adherent communities.
PMID- 28403172
TI - A first estimate of the structure and density of the populations of pet cats and
dogs across Great Britain.
AB - Policy development, implementation, and effective contingency response rely on a
strong evidence base to ensure success and cost-effectiveness. Where this
includes preventing the establishment or spread of zoonotic or veterinary
diseases infecting companion cats and dogs, descriptions of the structure and
density of the populations of these pets are useful. Similarly, such descriptions
may help in supporting diverse fields of study such as; evidence-based veterinary
practice, veterinary epidemiology, public health and ecology. As well as maps of
where pets are, estimates of how many may rarely, or never, be seen by
veterinarians and might not be appropriately managed in the event of a disease
outbreak are also important. Unfortunately both sources of evidence are absent
from the scientific and regulatory literatures. We make this first estimate of
the structure and density of pet populations by using the most recent national
population estimates of cats and dogs across Great Britain and subdividing these
spatially, and categorically across ownership classes. For the spatial model we
used the location and size of veterinary practises across GB to predict the local
density of pets, using client travel time to define catchments around practises,
and combined this with residential address data to estimate the rate of
ownership. For the estimates of pets which may provoke problems in managing a
veterinary or zoonotic disease we reviewed the literature and defined a
comprehensive suite of ownership classes for cats and dogs, collated estimates of
the sub-populations for each ownership class as well as their rates of
interaction and produced a coherent scaled description of the structure of the
national population. The predicted density of pets varied substantially, with the
lowest densities in rural areas, and the highest in the centres of large cities
where each species could exceed 2500 animals.km-2. Conversely, the number of pets
per household showed the opposite relationship. Both qualitative and quantitative
validation support key assumptions in the model structure and suggest the model
is useful at predicting the populations of cats at geographical scales important
for decision-making, although it also indicates where further research may
improve model performance. In the event of an animal health crisis, it appears
that almost all dogs could be brought under control rapidly. For cats, a
substantial and unknown number might never be bought under control and would be
less likely to receive veterinary support to facilitate surveillance and disease
management; we estimate this to be at least 1.5 million cats. In addition, the
lack of spare capacity to care for unowned cats in welfare organisations suggests
that any increase in their rate of acquisition of cats, or any decrease in the
rate of re-homing might provoke problems during a period of crisis.
PMID- 28403173
TI - Reference values of brachial-ankle pulse wave velocity according to age and blood
pressure in a central Asia population.
AB - BACKGROUND: Brachial-ankle pulse wave velocity (baPWV), a direct measure of
aortic stiffness, has increasingly become an important assessment for
cardiovascular risk. The present study established the reference and normal
values of baPWV in a Central Asia population in Xinjiang, China. METHODS: We
recruited participants from a central Asia population in Xinjiang, China. We
performed multiple regression analysis to investigate the determinants of baPWV.
The median and 10th-90th percentiles were calculated to establish the reference
and normal values based on these categories. RESULTS: In total, 5,757 Han
participants aged 15-88 years were included in the present study. Spearman
correlation analysis showed that age (r = 0.587, p < 0.001) and mean blood
pressure (MBP, r = 0.599, p <0.001) were the major factors influencing the values
of baPWV in the reference population. Furthermore, in the multiple linear
regression analysis, the standardized regression coefficients of age (0.445) and
MBP (0.460) were much higher than those of body mass index, triglyceride, and
glycemia (-0.054, 0.035, and 0.033, respectively). In the covariance analysis,
after adjustment for age and MBP, only diabetes was the significant independent
determinant of baPWV (p = 0.009). Thus, participants with diabetes were excluded
from the reference value population. The reference values ranged from 14.3 to
25.2 m/s, and the normal values ranged from 13.9 to 21.2 m/s. CONCLUSIONS: This
is the first study that has established the reference and normal values for baPWV
according to age and blood pressure in a Central Asia population.
PMID- 28403174
TI - Exercise in vivo marks human myotubes in vitro: Training-induced increase in
lipid metabolism.
AB - BACKGROUND AND AIMS: Physical activity has preventive as well as therapeutic
benefits for overweight subjects. In this study we aimed to examine effects of in
vivo exercise on in vitro metabolic adaptations by studying energy metabolism in
cultured myotubes isolated from biopsies taken before and after 12 weeks of
extensive endurance and strength training, from healthy sedentary normal weight
and overweight men. METHODS: Healthy sedentary men, aged 40-62 years, with normal
weight (body mass index (BMI) < 25 kg/m2) or overweight (BMI >= 25 kg/m2) were
included. Fatty acid and glucose metabolism were studied in myotubes using
[14C]oleic acid and [14C]glucose, respectively. Gene and protein expressions, as
well as DNA methylation were measured for selected genes. RESULTS: The 12-week
training intervention improved endurance, strength and insulin sensitivity in
vivo, and reduced the participants' body weight. Biopsy-derived cultured human
myotubes after exercise showed increased total cellular oleic acid uptake (30%),
oxidation (46%) and lipid accumulation (34%), as well as increased fractional
glucose oxidation (14%) compared to cultures established prior to exercise. Most
of these exercise-induced increases were significant in the overweight group,
whereas the normal weight group showed no change in oleic acid or glucose
metabolism. CONCLUSIONS: 12 weeks of combined endurance and strength training
promoted increased lipid and glucose metabolism in biopsy-derived cultured human
myotubes, showing that training in vivo are able to induce changes in human
myotubes that are discernible in vitro.
PMID- 28403175
TI - Altered cortical and subcortical connectivity due to infrasound administered near
the hearing threshold - Evidence from fMRI.
AB - In the present study, the brain's response towards near- and supra-threshold
infrasound (IS) stimulation (sound frequency < 20 Hz) was investigated under
resting-state fMRI conditions. The study involved two consecutive sessions. In
the first session, 14 healthy participants underwent a hearing threshold-as well
as a categorical loudness scaling measurement in which the individual loudness
perception for IS was assessed across different sound pressure levels (SPL). In
the second session, these participants underwent three resting-state
acquisitions, one without auditory stimulation (no-tone), one with a monaurally
presented 12-Hz IS tone (near-threshold) and one with a similar tone above the
individual hearing threshold corresponding to a 'medium loud' hearing sensation
(supra-threshold). Data analysis mainly focused on local connectivity measures by
means of regional homogeneity (ReHo), but also involved independent component
analysis (ICA) to investigate inter-regional connectivity. ReHo analysis revealed
significantly higher local connectivity in right superior temporal gyrus (STG)
adjacent to primary auditory cortex, in anterior cingulate cortex (ACC) and, when
allowing smaller cluster sizes, also in the right amygdala (rAmyg) during the
near-threshold, compared to both the supra-threshold and the no-tone condition.
Additional independent component analysis (ICA) revealed large-scale changes of
functional connectivity, reflected in a stronger activation of the right amygdala
(rAmyg) in the opposite contrast (no-tone > near-threshold) as well as the right
superior frontal gyrus (rSFG) during the near-threshold condition. In summary,
this study is the first to demonstrate that infrasound near the hearing threshold
may induce changes of neural activity across several brain regions, some of which
are known to be involved in auditory processing, while others are regarded as
keyplayers in emotional and autonomic control. These findings thus allow us to
speculate on how continuous exposure to (sub-)liminal IS could exert a pathogenic
influence on the organism, yet further (especially longitudinal) studies are
required in order to substantialize these findings.
PMID- 28403176
TI - Faster flux of neurotransmitter glutamate during seizure - Evidence from 13C
enrichment of extracellular glutamate in kainate rat model.
AB - The objective is to examine how the flux of neurotransmitter glutamate from
neurons to the extracellular fluid, as measured by the rate of 13C enrichment of
extracellular glutamate (GLUECF), changes in response to seizures in the kainate
induced rat model of temporal-lobe epilepsy. Following unilateral
intrahippocampal injection of kainate, GLUECF was collected by microdialysis from
the CA1/CA3 region of awake rats, in combination with EEG recording of chronic
phase recurrent seizures and intravenous infusion of [2,5-13C]glucose. The 13C
enrichment of GLUECF C5 at ~ 10 picomol level was measured by gas-chromatography
mass-spectrometry. The rate of 13C enrichment, expressed as the increase of the
fractional enrichment/min, was 0.0029 +/- 0.0001/min in frequently seizing rats
(n = 4); this was significantly higher (p < 0.01) than in the control (0.00167 +/
0.0001/min; n = 6) or in rats with infrequent seizures (0.00172 +/- 0.0001/min;
n = 6). This result strongly suggests that the flux of the excitatory
neurotransmitter from neurons to the extracellular fluid is significantly
increased by frequent seizures. The extracellular [12C + 13C]glutamate
concentration increased progressively in frequently seizing rats. Taken together,
these results strongly suggest that the observed seizure-induced high flux of
glutamate overstimulated glutamate receptors, which triggered a chain reaction of
excitation in the CA3 recurrent glutamatergic networks. The rate of 13C
enrichment of extracellular glutamine (GLNECF) at C5 was 0.00299 +/- 0.00027/min
in frequently seizing rats, which was higher (p < 0.05) than in controls (0.00227
+/- 0.00008/min). For the first time in vivo, this study examined the effects of
epileptic seizures on fluxes of the neurotransmitter glutamate and its precursor
glutamine in the extracellular fluid of the hippocampus. The advantages,
limitations and the potential for improvement of this approach for pre-clinical
and clinical studies of temporal-lobe epilepsy are discussed.
PMID- 28403177
TI - Genetic diversity and population structure of native maize populations in Latin
America and the Caribbean.
AB - This study describes the genetic diversity and population structure of 194 native
maize populations from 23 countries of Latin America and the Caribbean. The
germplasm, representing 131 distinct landraces, was genetically characterized as
population bulks using 28 SSR markers. Three main groups of maize germplasm were
identified. The first, the Mexico and Southern Andes group, highlights the Pre
Columbian and modern exchange of germplasm between North and South America. The
second group, Mesoamerica lowland, supports the hypothesis that two separate
human migration events could have contributed to Caribbean maize germplasm. The
third, the Andean group, displayed early introduction of maize into the Andes,
with little mixing since then, other than a regional interchange zone active in
the past. Events and activities in the pre- and post-Columbian Americas including
the development and expansion of pre-Columbian cultures and the arrival of
Europeans to the Americas are discussed in relation to the history of maize
migration from its point of domestication in Mesoamerica to South America and the
Caribbean through sea and land routes.
PMID- 28403178
TI - Relationship between epithelial cell adhesion molecule (EpCAM) overexpression and
gastric cancer patients: A systematic review and meta-analysis.
AB - OBJECTIVES: The epithelial cell adhesion molecule (EpCAM) is one of the most
commonly used markers of cancer stem cells (CSCs), but the clinical and
prognostic significance of EpCAM in gastric cancer (GC) remains disputable.
Motivated by heterogeneous and inconclusive results, we conducted a systematic
review and meta-analysis to systematically summarize and elucidate the
association between EpCAM overexpression and GC patients. METHODS: The PubMed,
Cochrane Library, Medline, Web of Knowledge and the China National Knowledge
Infrastructure (CNKI) databases were searched to identify relevant studies. The
RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random
effects models were applied depending on the presence of heterogeneity. The
pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to
estimate the associations between EpCAM and gastric cancer. For the significant
heterogeneity studies, sensitivity analyses were applied based on the population
to test the robustness of the pooled results and identify possible sources of
heterogeneity. RESULTS: A total of 11 studies including 1960 GC patients met our
inclusion criteria. The results of the meta-analyses revealed that there were
significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95%
CI: 2.13~4.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI:
29.21~220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.23~6.27,
P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95%
CI:0.29~0.99, P = 0.05). No significant associations were identified between
EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.66~1.19, P = 0.43), age (OR
= 1.13, 95% CI: 0.58~2.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.79~6.45,
P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.20~22.69, P = 0.52), TNM
stage (OR = 5.14, 95% CI: 0.77~34.37, P = 0.09), Lauren type (OR = 1.18, 95% CI:
0.08~16.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24).
However, due to significant heterogeneity in tumor stage, lymph node metastasis,
TNM stage, differentiation and Lauren type, these results should be taken
carefully. CONCLUSIONS: The meta-analysis demonstrated that the expression of
EpCAM in the gastric cancer group was greater than that in the control group.
Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode
metastasis and worse prognosis in gastric cancer. Due to significant
heterogeneity, the sensitivity analysis suggests that population factor may be an
important source of heterogeneity, and these results should be treated with
caution. EpCAM may be useful as a novel prognostic factor, and large-scale and
well-designed studies are needed to validate our results in the future.
PMID- 28403179
TI - New route for self-assembly of alpha-lactalbumin nanotubes and their use as
templates to grow silver nanotubes.
AB - Nanotubes are formed by self-assembly of alpha-lactalbumin milk protein following
a different route than established for the hydrolysis which involves V8 enzyme,
phosphate buffer and appropriate amounts of calcium at neutral pH. The resulting
nanotubes are used as templates for the growth of conductive silver nanotubes.
TEM, SEM-EDS, AFM and FTIR are used for characterization.
PMID- 28403180
TI - Amplification of a transgene within a long array of replication origins favors
higher gene expression in animal cells.
AB - Plasmids with both a mammalian replication initiation region (IR) and a matrix
attachment region (MAR) are spontaneously amplified in transfected cells, and
generate extrachromosomal double minute (DM) or chromosomal homogeneously
staining region (HSR). We previously isolated the shortest core IR (G5) required
for gene amplification. In this study, we ligated the G5 DNA to create direct or
inverted repeats, mixed the repeats with an expression plasmid, and transfected
the mixture into human COLO 320DM or hamster CHO DG44 cells. Consequently, we
found that the transfected sequence generated DMs or HSR where, surprisingly, the
plasmid sequence was embedded within a long stretch of G5 sequences. The
amplified structure from the direct G5 repeats was stable, whereas that from the
inverted repeats was not. The amplification might be explained by the efficient
replication/multimerization of the G5 repeat and recombination with the co
transfected plasmid in an extrachromosomal context. The product might then be
integrated into a chromosome arm to generate a HSR. The expression from the
plasmid within the long G5 array was much higher than that from a simple plasmid
repeat. Because G5 is a core IR that favors gene expression, a long array of G5
provides an excellent environment for gene expression from the embedded plasmid.
PMID- 28403181
TI - Mutational spectrum of Chinese LGMD patients by targeted next-generation
sequencing.
AB - This study aimed to study the diagnostic value of targeted next-generation
sequencing (NGS) in limb-girdle muscular dystrophies (LGMDs), and investigate the
mutational spectrum of Chinese LGMD patients. We performed targeted NGS covering
420 genes in 180 patients who were consecutively suspected of LGMDs and underwent
muscle biopsies from January 2013 to May 2015. The association between genotype
and myopathological profiles was analyzed in the genetically confirmed LGMD
patients. With targeted NGS, one or more rare variants were detected in 138
patients, of whom 113 had causative mutations, 10 sporadic patients had one
pathogenic heterozygous mutation related to a recessive pattern of LGMDs, and 15
had variants of uncertain significance. No disease-causing mutation was found in
the remaining 42 patients. Combined with the myopathological findings, we
achieved a positive genetic diagnostic rate as 68.3% (123/180). Totally 105
patients were diagnosed as LGMDs with genetic basis. Among these 105 patients,
the most common subtypes were LGMD2B in 52 (49.5%), LGMD2A in 26 (24.8%) and LGMD
2D in eight (7.6%), followed by LGMD1B in seven (6.7%), LGMD1E in four (3.8%),
LGMD2I in three (2.9%), and LGMD2E, 2F, 2H, 2K, 2L in one patient (1.0%),
respectively. Although some characteristic pathological changes may suggest
certain LGMD subtypes, both heterogeneous findings in a certain subtype and
overlapping presentations among different subtypes were not uncommon. The
application of NGS, together with thorough clinical and myopathological
evaluation, can substantially improve the molecular diagnostic rate in LGMDs.
Confirming the genetic diagnosis in LGMD patients can help improve our
understanding of their myopathological changes.
PMID- 28403182
TI - Functional analysis of the GmESR1 gene associated with soybean regeneration.
AB - Plant regeneration can occur via in vitro tissue culture through somatic
embryogenesis or de novo shoot organogenesis. Transformation of soybean (Glycine
max) is difficult, hence optimization of the transformation system for soybean
regeneration is required. This study investigated ENHANCER OF SHOOT REGENERATION
1 (GmESR1), a soybean transcription factor that targets regeneration-associated
genes. Sequence analysis showed that GmESR1 contained a conserved 57 amino acid
APETALA 2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) DNA-binding domain. The relative
expression level of GmESR1 was highest in young embryos, flowers and stems in the
soybean cultivar 'Dongnong 50'. To examine the function of GmESR1, transgenic
Arabidopsis (Arabidopsis thaliana) and soybean plants overexpressing GmESR1 were
generated. In Arabidopsis, overexpression of GmESR1 resulted in accelerated seed
germination, and seedling shoot and root elongation. In soybean overexpression of
GmESR1 also led to faster seed germination, and shoot and root elongation. GmESR1
specifically bound to the GCC-box. The results provide a foundation for the
establishment of an efficient and stable transformation system for soybean.
PMID- 28403183
TI - Aquatic environmental DNA detects seasonal fish abundance and habitat preference
in an urban estuary.
AB - The difficulty of censusing marine animal populations hampers effective ocean
management. Analyzing water for DNA traces shed by organisms may aid assessment.
Here we tested aquatic environmental DNA (eDNA) as an indicator of fish presence
in the lower Hudson River estuary. A checklist of local marine fish and their
relative abundance was prepared by compiling 12 traditional surveys conducted
between 1988-2015. To improve eDNA identification success, 31 specimens
representing 18 marine fish species were sequenced for two mitochondrial gene
regions, boosting coverage of the 12S eDNA target sequence to 80% of local taxa.
We collected 76 one-liter shoreline surface water samples at two contrasting
estuary locations over six months beginning in January 2016. eDNA was amplified
with vertebrate-specific 12S primers. Bioinformatic analysis of amplified DNA,
using a reference library of GenBank and our newly generated 12S sequences,
detected most (81%) locally abundant or common species and relatively few (23%)
uncommon taxa, and corresponded to seasonal presence and habitat preference as
determined by traditional surveys. Approximately 2% of fish reads were commonly
consumed species that are rare or absent in local waters, consistent with
wastewater input. Freshwater species were rarely detected despite Hudson River
inflow. These results support further exploration and suggest eDNA will
facilitate fine-scale geographic and temporal mapping of marine fish populations
at relatively low cost.
PMID- 28403184
TI - Low prevalence of human enteropathogenic Yersinia spp. in brown rats (Rattus
norvegicus) in Flanders.
AB - Brown rats (Rattus norvegicus) have been identified as potential carriers of
Yersinia enterocolitica and Y. pseudotuberculosis, the etiological agents of
yersiniosis, the third most reported bacterial zoonosis in Europe.
Enteropathogenic Yersinia spp. are most often isolated from rats during
yersiniosis cases in animals and humans, and from rats inhabiting farms and
slaughterhouses. Information is however lacking regarding the extent to which
rats act as carriers of these Yersinia spp.. In 2013, 1088 brown rats across
Flanders, Belgium, were tested for the presence of Yersinia species by isolation
method. Identification was performed using MALDI-TOF MS, PCR on chromosomal- and
plasmid-borne virulence genes, biotyping and serotyping. Yersinia spp. were
isolated from 38.4% of the rats. Of these, 53.4% were designated Y.
enterocolitica, 0.7% Y. pseudotuberculosis and 49.0% other Yersinia species. Two
Y. enterocolitica possessing the virF-, ail- and ystA-gene were isolated.
Additionally, the ystB-gene was identified in 94.1% of the other Y.
enterocolitica isolates, suggestive for biotype 1A. Three of these latter
isolates simultaneously possessed the ail-virulence gene. Significantly more Y.
enterocolitica were isolated during winter and spring compared to summer. Based
on our findings we can conclude that brown rats are frequent carriers for various
Yersinia spp., including Y. pseudotuberculosis and (human pathogenic) Y.
enterocolitica which are more often isolated during winter and spring.
PMID- 28403185
TI - Correlation of choroidal thickness and ametropiain young adolescence.
AB - Choroid has been proposed to participate in the regulation of light refraction by
changing its thickness. The present study aims to analyze the characteristics of
choroidal thickness (CT), and its correlation with refractive error, axial length
and age in young ametropia. A total of 51 subjects (102 eyes), aged from 5 to 18
years old (mean age 10.04 +/-2.78 years), with ametropia were included in the
study. Choroidal imaging was obtained by enhanced depth imaging (EDI) of spectral
domain Optical Coherence Tomography (OCT). CT was horizontally measured at 5
locations in across fovea with 1mm interval. We found that the spherical
equivalent refractive diopter was from -7.25D to 1.6D (mean, -1.61D+/-1.82D), the
mean axial length was 24.14mm+/-1.14mm. The closer to the optic disc the thinner
the choroid is. CT between fovea and disc showed better correlation with
refractive error (p< 0,01), axial length (p<0.01) and age (P<0.05) than those
temporal to fovea. Our results indicated that the choroid is least thick around
the optic disc. Thickness between fovea and optic disc is significantly
associated with refractive error, axial length and age in growing adolescences.
This result may help us understand the function of choroid during ametropic
progression.
PMID- 28403186
TI - Binding of interferon reduces the force of unfolding for interferon receptor 1.
AB - Differential signaling of the type I interferon receptor (IFNAR) has been
correlated with the ability of its subunit, IFNAR1, to differentially recognize a
large spectrum of different ligands, which involves intricate conformational re
arrangements of multiple interacting domains. To shed light onto the structural
determinants governing ligand recognition, we compared the force-induced
unfolding of the IFNAR1 ectodomain when bound to interferon and when free, using
the atomic force microscope and steered molecular dynamics simulations.
Unexpectedly, we find that IFNAR1 is easier to mechanically unfold when bound to
interferon than when free. Analysis of the structures indicated that the origin
of the reduction in unfolding forces is a conformational change in IFNAR1 induced
by ligand binding.
PMID- 28403187
TI - Effectiveness of advertising availability of prenatal ultrasound on uptake of
antenatal care in rural Uganda: A cluster randomized trial.
AB - In rural Uganda pregnant women often lack access to health services, do not
attend antenatal care, and tend to utilize traditional healers/birth attendants.
We hypothesized that receiving a message advertising that "you will be able to
see your baby by ultrasound" would motivate rural Ugandan women who otherwise
might use a traditional birth attendant to attend antenatal care, and that those
women would subsequently be more satisfied with care. A cluster randomized trial
was conducted across eight rural sub-counties in southwestern Uganda. Sub
counties were randomized to a control arm, with advertisement of antenatal care
with no mention of portable obstetric ultrasound (four communities, n = 59), or
an intervention arm, with advertisement of portable obstetric ultrasound.
Advertisement of portable obstetric ultrasound was further divided into
intervention A) word of mouth advertisement of portable obstetric ultrasound and
antenatal care (one communitity, n = 16), B) radio advertisement of only
antenatal care and word of mouth advertisement of antenatal care and portable
obstetric ultrasound (one community, n = 7), or C) word of mouth + radio
advertisement of both antenatal care and portable obstetric ultrasound (two
communities, n = 75). The primary outcome was attendance to antenatal care. 159
women presented to antenatal care across eight sub-counties. The rate of
attendance was 65.1 (per 1000 pregnant women, 95% CI 38.3-110.4) where portable
obstetric ultrasound was advertised by radio and word of mouth, as compared to a
rate of 11.1 (95% CI 6.1-20.1) in control communities (rate ratio 5.9, 95% CI 2.6
13.0, p<0.0001). Attendance was also improved in women who had previously seen a
traditional healer (13.0, 95% CI 5.4-31.2) compared to control (1.5, 95% CI 0.5
5.0, rate ratio 8.7, 95% CI 2.0-38.1, p = 0.004). By advertising antenatal care
and portable obstetric ultrasound by radio attendance was significantly improved.
This study suggests that women can be motivated to attend antenatal care when
offered the concrete incentive of seeing their baby.
PMID- 28403188
TI - Molecular pathways associated with blood pressure and hexadecanedioate levels.
AB - The dicarboxylic acid hexadecanedioate is associated with increased blood
pressure (BP) and mortality in humans and feeding it to rats raises BP. Here we
aim to characterise the molecular pathways that influence levels of
hexadecanedioate linked to BP regulation, using genetic and transcriptomic
studies. The top associations for hexadecanedioate in a genome-wide association
scan (GWAS) conducted on 6447 individuals from the TwinsUK and KORA cohorts were
tested for association with BP and hypertension in the International Consortium
for BP and in a GWAS of BP extremes. Transcriptomic analyses correlating
hexadecanedioate with gene expression levels in adipose tissue in 740 TwinsUK
participants were further performed. GWAS showed 242 SNPs mapping to two
independent loci achieving genome-wide significance. In rs414056 in the SCLO1B1
gene (Beta(SE) = -0.088(0.006)P = 1.65 x 10-51, P < 1 x 10-51), the allele
previously associated with increased risk of statin associated myopathy is
associated with higher hexadecanedioate levels. However this SNP did not show
association with BP or hypertension. The top SNP in the second locus rs6663731
mapped to the intronic region of CYP4Z2P on chromosome 1 (0.045(0.007), P =
5.49x10-11). Hexadecanedioate levels also correlate with adipose tissue gene
expression of the 3 out of 4 CYP4 probes (P<0.05) and of alcohol dehydrogenase
probes (Beta(SE) = 0.12(0.02); P = 6.04x10-11). High circulating levels of
hexadecanedioate determine a significant effect of alcohol intake on BP (SBP:
1.12(0.34), P = 0.001; DBP: 0.70(0.22), P = 0.002), while no effect is seen in
the lower hexadecanedioate level group. In conclusion, levels in fat of ADH1A,
ADH1B and CYP4 encoding enzymes in the omega oxidation pathway, are correlated
with hexadecanedioate levels. Hexadecanedioate appears to regulate the effect of
alcohol on BP.
PMID- 28403189
TI - Rapid forest clearing in a Myanmar proposed national park threatens two newly
discovered species of geckos (Gekkonidae: Cyrtodactylus).
AB - Myanmar's recent transition from military rule towards a more democratic
government has largely ended decades of political and economic isolation.
Although Myanmar remains heavily forested, increased development in recent years
has been accompanied by exceptionally high rates of forest loss. In this study,
we document the rapid progression of deforestation in and around the proposed
Lenya National Park, which includes some of the largest remaining areas of
lowland evergreen rainforest in mainland Southeast Asia. The globally unique
forests in this area are rich in biodiversity and remain a critical stronghold
for many threatened and endangered species, including large charismatic fauna
such as tiger and Asian elephant. We also conducted a rapid assessment survey of
the herpetofauna of the proposed national park, which resulted in the discovery
of two new species of bent-toed geckos, genus Cyrtodactylus. We describe these
new species, C. lenya sp. nov. and C. payarhtanensis sp. nov., which were found
in association with karst (i.e., limestone) rock formations within mature lowland
wet evergreen forest. The two species were discovered less than 35 km apart and
are each known from only a single locality. Because of the isolated nature of the
karst formations in the proposed Lenya National Park, these geckos likely have
geographical ranges restricted to the proposed protected area and are threatened
by approaching deforestation. Although lowland evergreen rainforest has vanished
from most of continental Southeast Asia, Myanmar can still take decisive action
to preserve one of the most biodiverse places on Earth.
PMID- 28403190
TI - Prevalence and genotype distribution of hepatitis delta virus among chronic
hepatitis B carriers in Central Vietnam.
AB - Hepatitis D virus (HDV) infection plays an important role in liver diseases.
However, the molecular epidemiology and impact of HDV infection in chronic
hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed
to investigate the prevalence and genotype distribution of HDV among HBsAg
positive patients in Central Vietnam. 250 CHB patients were tested for HDV using
newly established HDV-specific RT-PCR techniques. HDV genotypes were determined
by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV
viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%).
Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients
with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected
patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings
indicate that HDV infection is highly prevalent and HDV-2 is predominant in
Central Vietnam. The data will add new information to the management of HBsAg
positive patients in a highly HBV endemic region to in- or exclude HDV infection
in terms of diagnostic and treatment options.
PMID- 28403192
TI - A novel Meloidogyne graminicola effector, MgGPP, is secreted into host cells and
undergoes glycosylation in concert with proteolysis to suppress plant defenses
and promote parasitism.
AB - Plant pathogen effectors can recruit the host post-translational machinery to
mediate their post-translational modification (PTM) and regulate their activity
to facilitate parasitism, but few studies have focused on this phenomenon in the
field of plant-parasitic nematodes. In this study, we show that the plant
parasitic nematode Meloidogyne graminicola has evolved a novel effector, MgGPP,
that is exclusively expressed within the nematode subventral esophageal gland
cells and up-regulated in the early parasitic stage of M. graminicola. The
effector MgGPP plays a role in nematode parasitism. Transgenic rice lines
expressing MgGPP become significantly more susceptible to M. graminicola
infection than wild-type control plants, and conversely, in planta, the silencing
of MgGPP through RNAi technology substantially increases the resistance of rice
to M. graminicola. Significantly, we show that MgGPP is secreted into host plants
and targeted to the ER, where the N-glycosylation and C-terminal proteolysis of
MgGPP occur. C-terminal proteolysis promotes MgGPP to leave the ER, after which
it is transported to the nucleus. In addition, N-glycosylation of MgGPP is
required for suppressing the host response. The research data provide an
intriguing example of in planta glycosylation in concert with proteolysis of a
pathogen effector, which depict a novel mechanism by which parasitic nematodes
could subjugate plant immunity and promote parasitism and may present a promising
target for developing new strategies against nematode infections.
PMID- 28403193
TI - Sexual function and satisfaction among heterosexual and sexual minority U.S.
adults: A cross-sectional survey.
AB - BACKGROUND: Despite known health disparities for sexual minorities, few studies
have described sexual function by sexual orientation using a robust approach to
measurement of sexual function. We compared recent sexual function and
satisfaction by sexual orientation among English-speaking US adults. METHODS AND
FINDINGS: Cross-sectional surveys were administered by KnowledgePanel(r) (GfK),
an online panel that uses address-based probability sampling and is
representative of the civilian, noninstitutionalized US population. Data were
collected in 2013 from the general population (n = 3314, 35% response rate) and
in 2014 from self-identified lesbian, gay, and bisexual adults (n = 1011, 50%
response rate). Sexual function and satisfaction were measured using the Patient
Reported Outcomes Measurement Information System(r) Sexual Function and
Satisfaction measure version 2.0 (PROMIS SexFS v2). The PROMIS SexFS v2 is a
comprehensive, customizable measurement system with evidence for validity in
diverse populations. A score of 50 (SD 10) on each domain corresponds to the
average for US adults sexually active in the past 30 days. We adjusted all
statistics for the complex sample designs and report differences within each sex
where the 95% CIs do not overlap, corresponding to p<0.01. Among US men who
reported any sexual activity in the past 30 days, there were no differences in
erectile function or orgasm-ability. Compared to heterosexual men, sexual
minority men reported higher oral dryness and lower orgasm-pleasure and
satisfaction. Compared to heterosexual men, gay men reported lower interest,
higher anal discomfort and higher oral discomfort. Among sexually active women,
there were no differences in the domains of vulvar discomfort-clitoral, orgasm
pleasure, or satisfaction. Compared to heterosexual women, sexual minority women
reported higher oral dryness. Lesbian women reported lower vaginal discomfort
than other women; lesbian women reported higher lubrication and orgasm-ability
than heterosexual women. Bisexual women reported higher interest, higher vulvar
discomfort-labial and higher anal discomfort than other women, as well as higher
oral discomfort compared to heterosexual women. CONCLUSIONS: Recent sexual
function and satisfaction differed by sexual orientation among US adults. Sexual
minority men and women had decrements in domains of sexual function that have not
traditionally been included in multi-dimensional self-report measures. Clinicians
should make themselves aware of their patients' sexual concerns and recognize
that sexual minority patients may be more vulnerable to certain sexual
difficulties than heterosexual patients.
PMID- 28403191
TI - Visceral adipose tissue but not subcutaneous adipose tissue is associated with
urine and serum metabolites.
AB - Obesity is a complex multifactorial phenotype that influences several metabolic
pathways. Yet, few studies have examined the relations of different body fat
compartments to urinary and serum metabolites. Anthropometric phenotypes
(visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the ratio
between VAT and SAT (VSR), body mass index (BMI), waist circumference (WC)) and
urinary and serum metabolite concentrations measured by nuclear magnetic
resonance spectroscopy were measured in a population-based sample of 228 healthy
adults. Multivariable linear and logistic regression models, corrected for
multiple testing using the false discovery rate, were used to associate
anthropometric phenotypes with metabolites. We adjusted for potential confounding
variables: age, sex, smoking, physical activity, menopausal status, estimated
glomerular filtration rate (eGFR), urinary glucose, and fasting status. In a
fully adjusted logistic regression model dichotomized for the absence or presence
of quantifiable metabolite amounts, VAT, BMI and WC were inversely related to
urinary choline (beta = -0.18, p = 2.73*10-3), glycolic acid (beta = -0.20,
0.02), and guanidinoacetic acid (beta = -0.12, p = 0.04), and positively related
to ethanolamine (beta = 0.18, p = 0.02) and dimethylamine (beta = 0.32, p =
0.02). BMI and WC were additionally inversely related to urinary glutamine and
lactic acid. Moreover, WC was inversely associated with the detection of serine.
VAT, but none of the other anthropometric parameters, was related to serum
essential amino acids, such as valine, isoleucine, and phenylalanine among men.
Compared to other adiposity measures, VAT demonstrated the strongest and most
significant relations to urinary and serum metabolites. The distinct relations of
VAT, SAT, VSR, BMI, and WC to metabolites emphasize the importance of accurately
differentiating between body fat compartments when evaluating the potential role
of metabolic regulation in the development of obesity-related diseases, such as
insulin resistance, type 2 diabetes, and cardiovascular disease.
PMID- 28403194
TI - Calculations of actual corneal astigmatism using total corneal refractive power
before and after myopic keratorefractive surgery.
AB - PURPOSE: To calculate actual corneal astigmatism using the total corneal
refractive astigmatism for the 4-mm apex zone of the Pentacam (TCRP4astig) and
keratometric astigmatism (Kastig) before and after photorefractive keratectomy or
laser in situ keratomileusis. METHODS: Uncomplicated 56 eyes after more than 6
months from the surgery were recruited by chart review. Various corneal
astigmatisms were measured using the Pentacam and autokeratometer before and
after surgery. Three eyes were excluded and 53 eyes of 38 subjects with with-the
rule astigmatism (WTR) were finally included. The astigmatisms were investigated
using polar value analysis. When TCRP4astig was set as an actual astigmatism, the
efficacy of arithmetic or coefficient adjustment of Kastig was evaluated using
bivariate analysis. RESULTS: The difference between the simulated keratometer
astigmatism of the Pentacam (SimKastig) and Kastig was strongly correlated with
the difference between TCRP4astig and Kastig. TCRP4astig was different from
Kastig in magnitude rather than meridian before and after surgery; the
preoperative difference was due to the posterior cornea only; however, the
postoperative difference was observed in both anterior and posterior parts. For
arithmetic adjustment, 0.28 D and 0.27 D were subtracted from the preoperative
and postoperative magnitudes of Kastig, respectively. For coefficient adjustment,
the preoperative and postoperative magnitudes of Kastig were multiplied by 0.80
and 0.66, respectively. By arithmetic or coefficient adjustment, the difference
between TCRP4astig and adjusted Kastig would be less than 0.75 D in magnitude for
95% of cases. CONCLUSIONS: Kastig was successfully adjusted to TCPR4astig before
and after myopic keratorefractive surgery in cases of WTR. For use of TCRP4astig
directly, SimKastig and Kastig should be matched.
PMID- 28403195
TI - Does ought imply can?
AB - Most philosophers believe that a person can have an obligation only insofar as
she is able to fulfil it, a principle generally referred to as "Ought Implies
Can". Arguably, this principle reflects something basic about the ordinary
concept of obligation. However, in a paper published recently in this journal,
Wesley Buckwalter and John Turri presented evidence for the conclusion that
ordinary people in fact reject that principle. With a series of studies, they
claimed to have demonstrated that, in people's judgements, obligations persist
irrespective of whether those who hold them have the ability to fulfil them. We
argue in this paper that due to some problems in their design, Buckwalter &
Turri's conclusions may not be warranted. We present the results of a series of
studies demonstrating the problems with their design and showing that, with an
improved design, people judge that obligation depends on ability after all.
PMID- 28403196
TI - Validation of automatic measurement of QT interval variability.
AB - BACKGROUND: Increased variability of beat-to-beat QT-interval durations on the
electrocardiogram (ECG) has been associated with increased risk for fatal and non
fatal cardiac events. However, techniques for the measurement of QT variability
(QTV) have not been validated since a gold standard is not available. In this
study, we propose a validation method and illustrate its use for the validation
of two automatic QTV measurement techniques. METHODS: Our method generates
artificial standard 12-lead ECGs based on the averaged P-QRS-T complexes from a
variety of existing ECG signals, with simulated intrinsic (QT interval) and
extrinsic (noise, baseline wander, signal length) variations. We quantified QTV
by a commonly used measure, short-term QT variability (STV). Using 28,800
simulated ECGs, we assessed the performance of a conventional QTV measurement
algorithm, resembling a manual QTV measurement approach, and a more advanced
algorithm based on fiducial segment averaging (FSA). RESULTS: The results for the
conventional algorithm show considerable median absolute differences between the
simulated and estimated STV. For the highest noise level, median differences were
4-6 ms in the absence of QTV. Increasing signal length generally yields more
accurate STV estimates, but the difference in performance between 30 or 60 beats
is small. The FSA algorithm proved to be very accurate, with most median absolute
differences less than 0.5 ms, even for the highest levels of disturbance.
CONCLUSIONS: Artificially constructed ECGs with a variety of disturbances allow
validation of QTV measurement procedures. The FSA algorithm provides highly
accurate STV estimates under varying signal conditions, and performs much better
than traditional beat-by-beat analysis. The fully automatic operation of the FSA
algorithm enables STV measurement in large sets of ECGs.
PMID- 28403197
TI - Correction: Discriminating between HuR and TTP binding sites using the k-spectrum
kernel method.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174052.].
PMID- 28403198
TI - Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis.
AB - OBJECTIVES: This study aimed to (1) compare outcome assessments in normal and
osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline
osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled,
crossover design. METHODS: Twenty cats were included after clinical examination,
blood work and full body radiographs were performed. In Phase 1, outcome
assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic
and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated
twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg)
orally for 19 days, with a 3-month washout period between treatments. Evaluations
were performed in normal and OA cats at baseline and consisted of: 1) peak
vertical force (PVF) after staircase exercise; 2) telemetered night-time motor
activity (NMA); and 3) response to mechanical temporal summation (RMTS). After
treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were
analysed with mixed model methods with an alpha-threshold of 5%. RESULTS: Phase
1: 1) PVF (% of body weight; mean +/- SD) was higher in normal (59 +/- 10.5) than
in OA cats (50.6 +/- 5.7) (p = 0.005); 2) NMA (no unit) was not different between
groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5
(23.5-30)] than in OA cats [14 (8.5-28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS
presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively).
No clinically important adverse-effects were observed. CONCLUSION: Outcome
assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS)
are discriminant of OA status. Mobility measured by NMA was not discriminant of
OA status, however it increased in OA cats with tramadol treatment. Nociceptive
hypersensitivity quantified by RMTS was evident in OA cats and was responsive to
tramadol treatment.
PMID- 28403199
TI - The plastoquinone pool of Nannochloropsis oceanica is not completely reduced
during bright light pulses.
AB - The lipid-producing model alga Nannochloropsis oceanica has a distinct
photosynthetic machinery. This organism possesses chlorophyll a as its only
chlorophyll species, and has a high ratio of PSI to PSII. This high ratio of PSI
to PSII may affect the redox state of the plastoquinone pool during exposure to
light, and consequently may play a role in activating photoprotection mechanisms.
We utilized pulse-amplitude modulated fluorometry to investigate the redox state
of the plastoquinone pool during and after bright light pulses. Our data indicate
that even very intense (5910 MUmol photons s-1m-2 of blue light having a
wavelength of 440 nm) light pulses of 0.8 second duration are not sufficient to
completely reduce the plastoquinone pool in Nannochloropsis. In order to achieve
extensive reduction of the plastoquinone pool by bright light pulses, anaerobic
conditions or an inhibitor of the photosynthetic electron transport chain has to
be utilized. The implication of this finding for the application of the widely
used saturating pulse method in algae is discussed.
PMID- 28403200
TI - Identification of potential biomarkers in donor cows for in vitro embryo
production by granulosa cell transcriptomics.
AB - The Ovum Pick Up-In vitro Production (OPU-IVP) of embryos is an advanced
reproductive technology used in cattle production but the complex biological
mechanisms behind IVP outcomes are not fully understood. In this study we
sequenced RNA of granulosa cells collected from Holstein cows at oocyte
aspiration prior to IVP, to identify candidate genes and biological mechanisms
for favourable IVP-related traits in donor cows where IVP was performed
separately for each animal. We identified 56 genes significantly associated with
IVP scores (BL rate, kinetic and morphology). Among these, BEX2, HEY2, RGN,
TNFAIP6 and TXNDC11 were negatively associated while Mx1 and STC1 were positively
associated with all IVP scores. Functional analysis highlighted a wide range of
biological mechanisms including apoptosis, cell development and proliferation and
four key upstream regulators (COX2, IL1, PRL, TRIM24) involved in these
mechanisms. We found a range of evidence that good IVP outcome is positively
correlated with early follicular atresia. Furthermore we showed that high genetic
index bulls can be used in breeding without reducing the IVP performances. These
findings can contribute to the development of biomarkers from follicular fluid
content and to improving Genomic Selection (GS) methods that utilize functional
information in cattle breeding, allowing a widespread large scale application of
GS-IVP.
PMID- 28403201
TI - Serum endotrophin, a type VI collagen cleavage product, is associated with
increased mortality in chronic kidney disease.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk of
end-stage renal disease (ESRD) and early mortality. The underlying
pathophysiological processes are not entirely understood but may include
dysregulation of extracellular matrix formation with accelerated systemic and
renal fibrosis. We assessed the relationship between endotrophin (ETP), a marker
of collagen type VI formation, and adverse outcomes in a cohort of patients with
CKD. METHODS: We measured serum ETP levels in 500 patients from the Renal
Impairment in Secondary Care (RIISC) study, a prospective observational study of
patients with high-risk CKD. Patients were followed up until death or progression
to ESRD. Cox regression analysis was used to assess the relationship between ETP
and risk of adverse outcomes. RESULTS: During a median follow-up time of 37
months, 104 participants progressed to ESRD and 66 died. ETP level was
significantly associated with progression to ESRD (HR 1.79 [95% CI 1.59-2.02] per
10 ng/mL increase; HR 11.05 [4.98-24.52] for highest vs lowest quartile; both
P<0.0001). ETP level was also significantly associated with mortality (HR 1.60
[1.35-1.89] per 10 ng/mL increase; HR 12.14 [4.26-34.54] for highest vs lowest
quartile; both P<0.0001). After adjustment for confounding variables, ETP was no
longer significantly associated with progression to ESRD but remained
independently associated with mortality (HR 1.51 [1.07-2.12] per 10 ng/mL
increase, P = 0.019). CONCLUSIONS: Serum ETP level is independently associated
with mortality in CKD. This study provides the basis for further exploratory work
to establish whether collagen type VI formation is mechanistically involved in
the increased mortality risk associated with CKD.
PMID- 28403202
TI - Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-alpha as a key for
entry.
AB - Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry
as ligands for host cell receptors and by promoting fusion of viral envelopes
with cellular membranes. Human cytomegalovirus (HCMV) has two alternative gH/gL
complexes, gH/gL/gO and gH/gL/UL128,130,131A which both shape the HCMV tropism.
By studying binding of HCMV particles to fibroblasts, we could for the first time
show that virion gH/gL/gO binds to platelet-derived growth factor-alpha (PDGFR
alpha) on the surface of fibroblasts and that gH/gL/gO either directly or
indirectly recruits gB to this complex. PDGFR-alpha functions as an entry
receptor for HCMV expressing gH/gL/gO, but not for HCMV mutants lacking the
gH/gL/gO complex. PDGFR-alpha-dependent entry is not dependent on activation of
PDGFR-alpha. We could also show that the gH/gL/gO-PDGFR-alpha interaction starts
the predominant entry pathway for infection of fibroblasts with free virus. Cell
associated virus spread is either driven by gH/gL/gO interacting with PDGFR-alpha
or by the gH/gL/UL128,130,131A complex. PDGFR-alpha-positive cells may thus be
preferred first target cells for infections with free virus which might have
implications for the design of future HCMV vaccines or anti-HCMV drugs.
PMID- 28403203
TI - Dynamics of triacylglycerol and EPA production in Phaeodactylum tricornutum under
nitrogen starvation at different light intensities.
AB - Lipid production in microalgae is highly dependent on the applied light
intensity. However, for the EPA producing model-diatom Phaeodactylum tricornutum,
clear consensus on the impact of incident light intensity on lipid productivity
is still lacking. This study quantifies the impact of different incident light
intensities on the biomass, TAG and EPA yield on light in nitrogen starved batch
cultures of P. tricornutum. The maximum biomass concentration and maximum TAG and
EPA contents were found to be independent of the applied light intensity. The
lipid yield on light was reduced at elevated light intensities (>100 MUmol m-2 s
1). The highest TAG yield on light (112 mg TAG molph-1) was found at the lowest
light intensity tested (60 MUmol m-2 s-1), which is still relatively low to
values reported in literature for other algae. Furthermore, mass balance analysis
showed that the EPA fraction in TAG may originate from photosynthetic membrane
lipids.
PMID- 28403204
TI - Improving specificity of Bordetella pertussis detection using a four target real
time PCR.
AB - The incidence of whooping cough, a contagious respiratory disease caused by
Bordetella pertussis, is on the rise despite existing vaccination programmes.
Similar, though usually milder, respiratory symptoms may be caused by other
members of the Bordetella genus: B. parapertussis, B. holmesii, and B.
bronchiseptica. Pertussis diagnosis is mostly done using PCR, but the use of
multiple targets is necessary in order to differentiate the different Bordetella
spp. with sufficient sensitivity and specificity. In this study we evaluate a
multiplex PCR assay for the differentiation of B. pertussis from other Bordetella
spp., using the targets IS481, IS1001, IS1002, and recA. Moreover, we
retrospectively explore the epidemiology of Bordetella spp. infections in
Belgium, using the aforementioned assay over a three-year period, from 2013 until
2015.
PMID- 28403205
TI - Spontaneous diseases in captive ratites (Struthioniformes) in northwestern
Germany: A retrospective study.
AB - A retrospective study was carried out to define the spectrum of spontaneous
diseases in ostriches and few other captive ratites, order Struthioniformes, in
northwestern Germany. The investigation included 71 ratites necropsied between
1968 and 2014. They consisted of 54 ostriches, 5 emus, and 12 rheas with 37
adults, 23 juveniles and 11 neonates and embryonated eggs. Necropsy reports were
reviewed, histologic preparations were re-examined and additional histochemical
and immunohistochemical stains were carried out in selected cases. In many
animals more than one morphologic diagnosis attributable to different disease
processes was found. In adult animals (n = 37), the most commonly altered organ
systems were the musculoskeletal system (49%), the digestive system (46%), and
the cardiovascular system (46%) affected by traumatic lesions, inflammatory and
degenerative changes, respectively. A spongy degeneration was found in the brain
(35%); however, immunohistochemistry and western blotting failed to detect
pathological prion protein. In juvenile animals (n = 23), the musculoskeletal
(44%) and the digestive system (43%) were mainly affected by traumatic and
inflammatory lesions, respectively. In embryonated eggs and neonates (n = 11) the
major cause of death was circulatory failure associated with generalized
subcutaneous edema as described for improper incubation conditions (64%).
Summarized, most of the findings observed in adult and juvenile ratites in
northwestern Germany are related to trauma, inflammatory and degenerative
disorders, whereas death in embryonated eggs and neonates was most likely related
to breeding conditions. A spongy encephalopathy awaits further studies to
elucidate cause and pathogenesis.
PMID- 28403206
TI - Persistent weight loss with a non-invasive novel medical device to change eating
behaviour in obese individuals with high-risk cardiovascular risk profile.
AB - : In evidence-based weight-loss programs weight regain is common after an initial
weight reduction. Eating slowly significantly lowers meal energy intake and
hunger ratings. Despite this knowledge, obese individuals do not implement this
behaviour. We, thus tested the hypothesis of changing eating behaviour with an
intra-oral medical device leading to constant weight reduction in overweight and
obesity. Six obese patients (6 men, age 56 +/- 14, BMI 29 +/- 2 kg / m2) with
increased CVRF profile were included in this prospective study. All patients had
been treated for obesity during the last 10 years in a single centre and had at
least 3 frustrate evidence-based diets. Patients received a novel non-invasive
intra-oral medical device to slow eating time. Further advice included not to
count calories, to avoid any other form of diet, to take their time with their
meals, and to eat whatever they liked. This device was used only during meals for
the first 4 to 8 weeks for a total of 88 [20-160] hours. Follow-up period was 23
[15-38] months. During this period, patients lost 11% [5-20%] (p<0.001) of their
initial weight. At 12 months, all patients had lost >5%, and 67% (4/6) achieved a
>10% bodyweight loss. In the course of the study, altered eating patterns were
observed. There were no complications with the medical device. Of note, all
patients continued to lose weight after the initial intervention period (p<0.001)
and none of them had weight regain. With this medical device, overweight and
obese patients with a history of previously frustrating attempts to lose weight
achieved a significant and sustained weight loss over two years. These results
warrant the ongoing prospective randomised controlled trial to prove concept and
mechanism of action. TRIAL REGISTRATION: German Clinical Trials Register
DRKS00011357.
PMID- 28403207
TI - Biosecurity messages are lost in translation to citizens: Implications for
devolving management to citizens.
AB - The increasing focus of marine biosecurity agencies on transferring management
responsibilities to citizens and industry begs the question whether devolved
responsibility is a viable option for creating biosecurity outcomes. We examined
recreational marine users' self-declared awareness of non-indigenous marine
species (NIMS) at six locations in Tasmania, Australia and evaluated the accuracy
of their awareness through recognition of four well-known NIMS with active
awareness campaigns. We also investigated whether the activities of recreational
marine users influence the accuracy of their NIMS recognition skills. We
generally found that respondents declare NIMS awareness (70.45%), yet we found
their recognition accuracy was variable ranging from low to fair (<10% to 54.95%)
and recreational activity did not influence accuracy. Based on our results, we
conclude that marine users' awareness does not predict accuracy and therefore
devolved management of biosecurity without additional resources may pose a risky
biosecurity management strategy.
PMID- 28403208
TI - Analogosedation during flexible bronchoscopy using a combination of midazolam,
propofol and fentanyl - A retrospective analysis.
AB - BACKGROUND: According to current guidelines flexible bronchoscopy is usually
performed under sedation. Previously it has been demonstrated that combined
sedation with e. g. the combination of midazolam and propofol or an opioid might
have several advantages over sedation with just one sedative drug. However,
little is known about the efficacy and safety of combined sedation with
midazolam, fentanyl and propofol (MFP) compared to sedation with midazolam and
fentanyl (MF) or midazolam and propofol (MP). METHODS: We carried out a
retrospective analysis of bronchoscopies performed under triple (MFP) or double
sedation (MF and MP) in an academic hospital. 1392 procedures were analyzed (MFP:
n = 824; MF: n = 272; MP: n = 296). In particular, we compared the occurrence of
complications and the dosage of administered sedative drugs between the groups.
RESULTS: The occurrence of adverse events (MFP vs. MF: odds ratio (OR) 1.116 [95%
CI 0.7741 to 1.604]; MFP vs. MP: OR 0.8296 [95% CI 0.5939 to 1.16] and severe
adverse events (MFP vs. MF: OR 1.581 [95% CI 0.5594 to 4.336]; MFP vs. MP: OR
3.47 [95% CI 0.908 to 15.15]; all p>0.05) was similar in all groups. The dosage
of midazolam was lower in the MFP compared to the MF or MP group (MFP vs. MF:
Cohen's d 0.075; MFP vs. MP: Cohen's d 0.225; all p<0.001). In addition patients
in the MFP group received significantly less propofol compared to the MP group
(Cohen's d 1.22; p<0.001). CONCLUSIONS: In summary we were able to demonstrate
that triple sedation can safely be administered during flexible bronchoscopy and
is associated with a reduced dosage of midazolam and propofol.
PMID- 28403209
TI - Correction: How Much Can the USA Reduce Health Care Costs by Reducing Smoking?
AB - [This corrects the article DOI: 10.1371/journal.pmed.1002021.].
PMID- 28403210
TI - Molecular adsorbent recirculating system (MARS) in acute liver injury and graft
dysfunction: Results from a case-control study.
AB - BACKGROUND: The primary therapeutic goals in the treatment of liver injury are to
support liver regeneration or bridge the gap to liver transplantation (LT).
Molecular adsorbent recirculating system (MARS) therapy has shown beneficial
effects for specific symptoms of liver failure; however, general survival
advantages have not yet been demonstrated. AIM: We studied the effects of MARS
therapy compared to standard medical treatment (SMT) in two patient cohorts: in
patients with an acute liver injury and in those with graft dysfunction (GD).
METHODS: We report on our experience over a 6.5-year period with 73 patients
treated with SMT or with SMT and MARS (MARS group). In total, 53 patients
suffered from acute liver injury in their native liver without a preexisting
liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD
after LT (SMT: n = 10, MARS: n = 10). RESULTS: The entire cohort was
predominantly characterized by hemodynamically and respiratorily stable patients
with a low hepatic encephalopathy (HE) grade and a model of end-stage liver
disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS
group, the median number of extracorporeal therapy sessions was four (range = 3-5
sessions). Independent of the underlying etiology, MARS improved the patients'
bilirubin values in the short term compared to SMT alone. In patients with acute
liver injury, this response was sustained even after the end of MARS therapy. By
contrast, the majority of patients with GD and an initial response to MARS
therapy experienced worsened hyperbilirubinemia. No differences in 28-day
mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0
15.3); SMT 3.3% (95% CI: 0-9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0-44.7),
SMT 11.1% (95% CI: 0-31.7), p = 0.478). CONCLUSIONS: Although it did not improve
28-day mortality, MARS therapy improved the short-term response in patients with
acute liver injury as well as in those with GD. In cases of acute hepatic injury,
the use of MARS therapy resulted in the sustained stabilization of liver function
and improved liver regeneration. A short-term response to MARS may predict the
future course of the disease.
PMID- 28403211
TI - The potential impact and cost of focusing HIV prevention on young women and men:
A modeling analysis in western Kenya.
AB - OBJECTIVE: We compared the impact and costs of HIV prevention strategies focusing
on youth (15-24 year-old persons) versus on adults (15+ year-old persons), in a
high-HIV burden context of a large generalized epidemic. DESIGN: Compartmental
age-structured mathematical model of HIV transmission in Nyanza, Kenya.
INTERVENTIONS: The interventions focused on youth were high coverage HIV testing
(80% of youth), treatment at diagnosis (TasP, i.e., immediate start of
antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive
diagnosed youth, male circumcision for HIV-negative young men, pre-exposure
prophylaxis (PrEP) for high-risk HIV-negative females (ages 20-24 years), and
cash transfer for in-school HIV-negative girls (ages 15-19 years). Permutations
of these were compared to adult-focused HIV testing coverage with condoms and
TasP. RESULTS: The youth-focused strategy with ART treatment at diagnosis and
condom use without adding interventions for HIV-negative youth performed better
than the adult-focused strategy with adult testing reaching 50-60% coverage and
TasP/condoms. Over the long term, the youth-focused strategy approached the
performance of 70% adult testing and TasP/condoms. When high coverage male
circumcision also is added to the youth-focused strategy, the combined
intervention outperformed the adult-focused strategy with 70% testing, for at
least 35 years by averting 94,000 more infections, averting 5.0 million more
disability-adjusted life years (DALYs), and saving US$46.0 million over this
period. The addition of prevention interventions beyond circumcision to the youth
focused strategy would be more beneficial if HIV care costs are high, or when
program delivery costs are relatively high for programs encompassing HIV testing
coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to
combination prevention programs among youth. CONCLUSION: For at least the next
three decades, focusing in high burden settings on high coverage HIV testing, ART
treatment upon diagnosis, condoms and male circumcision among youth may
outperform adult-focused ART treatment upon diagnosis programs, unless the adult
testing coverage in these programs reaches very high levels (>70% of all adults
reached) at similar program costs. Our results indicate the potential importance
of age-targeting for HIV prevention in the current era of 'test and start, ending
AIDS' goals to ameliorate the HIV epidemic globally.
PMID- 28403212
TI - Longitudinal monitoring of Gaussia and Nano luciferase activities to concurrently
assess ER calcium homeostasis and ER stress in vivo.
AB - The endoplasmic reticulum (ER) is essential to many cellular processes including
protein processing, lipid metabolism and calcium storage. The ability to
longitudinally monitor ER homeostasis in the same organism would offer insight
into progressive molecular and cellular adaptations to physiologic or pathologic
states, but has been challenging. We recently described the creation of a Gaussia
luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc
SERCaMP) to longitudinally monitor ER calcium homeostasis. Here we describe a
complementary tool to measure the unfolded protein response (UPR), utilizing a
UPRE-driven secreted Nano luciferase (UPRE-secNLuc) to examine the activating
transcription factor-6 (ATF6) and inositol-requiring enzyme 1 (IRE1) pathways of
the UPR. We observed an upregulation of endogenous ATF6- and XBP1-regulated genes
following pharmacologically-induced ER stress that was consistent with
responsiveness of the UPRE sensor. Both GLuc and NLuc-based reporters have
favorable properties for in vivo studies, however, they are not easily used in
combination due to overlapping substrate activities. We describe a method to
measure the enzymatic activities of both reporters from a single sample and
validated the approach using culture medium and rat blood samples to measure GLuc
SERCaMP and UPRE-secNLuc. Measuring GLuc and NLuc activities from the same sample
allows for the robust and quantitative measurement of two cellular events or cell
populations from a single biological sample. This study is the first to describe
the in vivo measurement of UPRE activation by sampling blood, using an approach
that allows concurrent interrogation of two components of ER homeostasis.
PMID- 28403213
TI - M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting
the secretory pathway in neoplastic mast cells.
AB - Gain-of-function mutations in Kit receptor tyrosine kinase result in the
development of a variety of cancers, such as mast cell tumours, gastrointestinal
stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug
imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit
positive cancers. However, mutations in the Kit kinase domain, which are
frequently found in neoplastic mast cells, confer an imatinib resistance, and
cancers expressing the mutants can proliferate in the presence of imatinib.
Recently, we showed that in neoplastic mast cells that endogenously express an
imatinib-resistant Kit mutant, Kit causes oncogenic activation of the
phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer
and activator of transcription 5 (STAT5) but only on endolysosomes and on the
endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition
of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2
methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA
treated cells, Kit localization in the ER is significantly increased, whereas
endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic
transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation
without affecting the association of Kit with PI3K, indicating that ER-localized
Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib
suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic
Akt activation. Results of our M-COPA treatment assay show that Kit can activate
Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570,
Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that
these five tyrosine residues are all phosphorylated before mutant Kit reaches the
plasma membrane (PM). Our study provides evidence that Kit is tyrosine
phosphorylated soon after synthesis on the ER but is unable to activate Akt and
also demonstrates that M-COPA is efficacious for growth suppression of neoplastic
mast cells.
PMID- 28403214
TI - Antibody-independent capture of circulating tumor cells of non-epithelial origin
with the ApoStream(r) system.
AB - Circulating tumor cells (CTCs) are increasingly employed for research and
clinical monitoring of cancer, though most current methods do not permit the
isolation of non-epithelial tumor cells. Furthermore, CTCs isolated with antibody
dependent methods are not suitable for downstream experimental uses, including in
vitro culturing and implantation in vivo. In the present study, we describe the
development, validation, and transfer across laboratories of a new antibody
independent device for the enrichment of CTCs from blood samples of patients with
various cancer diagnoses. The ApoStream(r) device uses dielectrophoresis (DEP)
field-flow assist to separate non-hematopoietic cells from the peripheral blood
mononuclear fraction by exposing cells in a laminar flow stream to a critical
alternating current frequency. The ApoStream(r) device was calibrated and
validated in a formal cross-laboratory protocol using 3 different cancer cell
lines spanning a range of distinct phenotypes (A549, MDA-MB-231, and ASPS-1). In
spike-recovery experiments, cancer cell recovery efficiencies appeared
independent of spiking level and averaged between 68% and 55%, depending on the
cell line. No inter-run carryover was detected in control samples. Moreover, the
clinical-readiness of the device in the context of non-epithelial cancers was
evaluated with blood specimens from fifteen patients with metastatic sarcoma. The
ApoStream(r) device successfully isolated CTCs from all patients with sarcomas
examined, and the phenotypic heterogeneity of the enriched cells was demonstrated
by fluorescence in situ hybridization or with multiplex immunophenotyping panels.
Therefore, the ApoStream(r) technology expands the clinical utility of CTC
evaluation to mesenchymal cancers.
PMID- 28403215
TI - Rv3634c from Mycobacterium tuberculosis H37Rv encodes an enzyme with UDP-Gal/Glc
and UDP-GalNAc 4-epimerase activities.
AB - A bioinformatics study revealed that Mycobacterium tuberculosis H37Rv (Mtb)
contains sequence homologs of Campylobacter jejuni protein glycosylation enzymes.
The ORF Rv3634c from Mtb was identified as a sequence homolog of C. jejuni UDP
Gal/GalNAc 4-epimerase. This study reports the cloning of Rv3634c and its
expression as an N-terminal His-tagged protein. The recombinant protein was shown
to have UDP-Gal/Glc 4-epimerase activity by GOD-POD assay and by reverse phase
HPLC. This enzyme was shown to have UDP-GalNAc 4-epimerase activity also.
Residues Ser121, Tyr146 and Lys150 were shown by site-directed mutagenesis to be
important for enzyme activity. Mutation of Ser121 and Tyr146 to Ala and Phe,
respectively, led to complete loss of activity whereas mutation of Lys150 to Arg
led to partial loss of activity. There were no gross changes in the secondary
structures of any of these three mutants. These results suggest that Ser121 and
Tyr146 are essential for epimerase activity of Rv3634c. UDP-Gal/Glc 4-epimerases
from other organisms also have a catalytic triad consisting of Ser, Tyr and Lys.
The triad carries out proton transfer from nucleotide sugar to NAD+ and back,
thus effecting the epimerization of the substrate. Addition of NAD+ to Lys150
significantly abrogates the loss of activity, suggesting that, as in other
epimerases, NAD+ is associated with Rv3634c.
PMID- 28403216
TI - Efficacy and safety of aspirin in patients with peripheral vascular disease: An
updated systematic review and meta-analysis of randomized controlled trials.
AB - BACKGROUND: Although considered a cornerstone therapy, the efficacy and safety of
aspirin for prevention of ischemic events in patients with peripheral vascular
disease (PVD) remains uncertain. Thus, we aimed to evaluate aspirin use in both
symptomatic and asymptomatic patients with PVD. METHODS: An electronic search of
databases was conducted from inception until January 2017 for all randomized
trials comparing aspirin with either placebo or control (no aspirin) in patients
with PVD. The primary efficacy outcome was all-cause mortality, and the primary
safety outcome was major bleeding. Other outcomes of interest were major adverse
cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), stroke
and intracranial hemorrhage. Random-effects summary risk ratios (RR) were
calculated using Der-Simonian and Liard model. The quality of evidence was
assessed by GRADE tool and Cochrane risk of bias assessment tool. RESULTS: A
total of 6,560 patients from 11 trials were included. Only two trials were
considered to have low risk of bias. Compared with control, aspirin was
associated with similar incidence of all-cause mortality (RR = 0.93, 95%
confidence interval [CI] 0.8-1.1), MACCE (RR = 1.0, 95% CI 0.83-1.20), MI (RR =
0.91, 95% CI 0.67-1.23) and stroke (RR = 0.72, 95% CI 0.43-1.22), major bleeding
(RR = 1.59, 95% CI 0.96-2.62) and intracranial hemorrhage (RR = 1.38, 95% CI 0.59
3.21). CONCLUSIONS: Aspirin use in PVD might not be associated with improved
cardiovascular outcomes or worse bleeding outcomes. Larger randomized trials
assessing the efficacy and safety of aspirin in the contemporary era are
mandatory to confirm the current findings. Guideline recommendations regarding
the use of aspirin among patients with PVD need to be updated.
PMID- 28403217
TI - Embryonic loss of human females with partial trisomy 19 identifies region
critical for the single active X.
AB - To compensate for the sex difference in the number of X chromosomes, human
females, like human males have only one active X. The other X chromosomes in
cells of both sexes are silenced in utero by XIST, the Inactive X Specific
Transcript gene, that is present on all X chromosomes. To investigate the means
by which the human active X is protected from silencing by XIST, we updated the
search for a key dosage sensitive XIST repressor using new cytogenetic data with
more precise resolution. Here, based on a previously unknown sex bias in copy
number variations, we identify a unique region in our genome, and propose
candidate genes that lie within, as they could inactivate XIST. Unlike males, the
females who duplicate this region of chromosome 19 (partial 19 trisomy) do not
survive embryogenesis; this preimplantation loss of females may be one reason
that more human males are born than females.
PMID- 28403218
TI - Association of arginase I or nitric oxide-related factors with job strain in
healthy workers.
AB - This study evaluated the associations between job strain and arginase I in 378
healthy Japanese factory workers by a cross-sectional study measuring nitric
oxide (NO)-related parameters (arginase I, L-arginine, exhaled nitric oxide
(FeNO), and NOx), clinical parameters, and job strain using a Japanese version of
the Job Content Questionnaire by Karasek. Arginase I and FEV1% were negatively
correlated with job strain and positively correlated with job control and social
support. FeNO and hs-CRP were negatively correlated with job strain. Multiple
regression analysis showed negative association of arginase I with job strain and
positive association with job control and social support in females. It is
concluded that serum levels of arginase I may be useful biomarkers for the
diagnosis of job stress in healthy female workers, although many factors can be
influencing the data.
PMID- 28403219
TI - Incidental hepatocellular carcinoma after liver transplantation: Prevalence,
histopathological features and prognostic impact.
AB - BACKGROUND: Incidental hepatocellular carcinoma (iHCC) is a histological finding
after liver transplantation (LT) which relevance has been scarcely studied. AIMS:
to describe the histopathological features of iHCC and to determine its
prognostic impact in terms of tumor recurrence and overall survival. METHODS:
Observational study including 451 consecutive adult LT patients (2000-2013).
Patients aged<18, retransplanted or with early postoperative death were excluded.
Median follow-up after LT was 58 months. Multiple Cox's regression was used to
assess the prognostic impact of iHCC on tumor recurrence and mortality while
controlling for potential confounders. RESULTS: 141 patients had known HCC before
LT (31.3%). Among the remaining 310 patients, the prevalence of iHCC was 8.7% (n
= 27). In the explanted liver, 36.2% of patients with known HCC and 25.9% of
patients with iHCC trespassed Milan criteria (p = 0.30). Patients with known and
iHCC had similar rates of multinodular disease (50.4% vs 55.6%; p = 0.62),
macrovascular invasion (6.5% vs 3.7%; p = 0.58), microvascular invasion (12.9% vs
14.8%; p = 0.76) and moderate-poor tumor differentiation (53.9% vs 70.4%; p =
0.09). In the multivariate analysis, iHCC and known HCC had identical recurrence
free survival after controlling for histological features (RR = 1.06, 95%CI 0.36
3.14; p = 0.90). Cumulative 5-year overall survival rates were similar between
patients with known and iHCC (65% vs 52.8% respectively; log rank p = 0.44), but
significantly inferior as compared with patients without HCC (77.8%) (p = 0.002
and p = 0.007 respectively). Indeed, in the overall cohort, iHCC was an
independent predictor of mortality (RR = 3.02; 95%CI 1.62-5.65; p = 0.001).
CONCLUSION: The risk of tumor recurrence after LT is similar in patients with
iHCC and known HCC. A close imaging surveillance is strongly recommended for
patients awaiting LT in order to detect HCC prior to LT, thus allowing for an
adequate selection of candidates, prioritization and indication of bridging
therapies.
PMID- 28403221
TI - Correction: Thermal stability and structural changes in bacterial toxins
responsible for food poisoning.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172445.].
PMID- 28403220
TI - A derivative of platelet-derived growth factor receptor alpha binds to the trimer
of human cytomegalovirus and inhibits entry into fibroblasts and endothelial
cells.
AB - Human cytomegalovirus (HCMV) is a widely distributed herpesvirus that causes
significant morbidity in immunocompromised hosts. Inhibitors of viral DNA
replication are available, but adverse effects limit their use. Alternative
antiviral strategies may include inhibition of entry. We show that soluble
derivatives of the platelet-derived growth factor receptor alpha (PDGFR-alpha), a
putative receptor of HCMV, can inhibit HCMV infection of various cell types. A
PDGFR-alpha-Fc fusion protein binds to and neutralizes cell-free virus particles
at an EC50 of 10-30 ng/ml. Treatment of particles reduced both attachment to and
fusion with cells. In line with the latter, PDGFR-alpha-Fc was also effective
when applied postattachment. A peptide scan of the extracellular domain of PDGFR
alpha identified a 40mer peptide that inhibits infection at an EC50 of 1-2
nmol/ml. Both, peptide and fusion protein, were effective against various HCMV
strains and are hence promising candidates for the development of novel anti-HCMV
therapies.
PMID- 28403222
TI - Comorbidity and dementia: A nationwide survey in Taiwan.
AB - BACKGROUND: Comorbid medical diseases are highly prevalent in the geriatric
population, imposing hardship on healthcare services for demented individuals.
Dementia also complicates clinical care for other co-existing medical conditions.
This study investigated the comorbidities associated with dementia in the elderly
population aged 65 years and over in Taiwan. METHODS: We conducted a nationwide,
population-based, cross-sectional survey; participants were selected by
computerized random sampling from all 19 Taiwan counties between December 2011
and March 2013. After exclusion of incomplete or erroneous data, 8,456 subjects
were enrolled. Of them, 6,183 were cognitively normal (control group), 1,576 had
mild cognitive impairment (MCI), and 697 had dementia. We collected information
about types of comorbidities (i.e., vascular risk factors, lung diseases, liver
diseases, gastrointestinal diseases, and cancers), Charlson comorbidity index
score, and demographic variables to compare subjects with normal cognition, MCI,
and dementia. RESULTS: Regardless of the cognitive condition, over 60% of the
individuals in each group had at least one comorbid disease. The proportion of
subjects possessing at least three comorbidities was higher in those with
cognitive impairment (MCI 20.9%, dementia 27.3%) than in control group (15%).
Hypertension and diabetes mellitus were the most common comorbidities. The mean
number of comorbidities and Charlson comorbidity index score were greater in MCI
and dementia groups than in control group. Logistic regression demonstrated that
the comorbidities significantly associated with MCI and dementia were
cerebrovascular disease (OR 3.35, CI 2.62-4.28), cirrhosis (OR 3.29, CI 1.29
8.41), asthma (OR 1.56, CI 1.07-2.27), and diabetes mellitus (OR 1.24, CI 1.07
1.44). CONCLUSION: Multiple medical comorbid diseases are common in older adults,
especially in those with cognitive impairment. Cerebrovascular disease,
cirrhosis, asthma, and diabetes mellitus are important contributors to cognitive
deterioration in the elderly. Efforts to lower cumulative medical burden in the
geriatric population may benefit cognitive function.
PMID- 28403224
TI - HSTLBO: A hybrid algorithm based on Harmony Search and Teaching-Learning-Based
Optimization for complex high-dimensional optimization problems.
AB - Harmony Search (HS) and Teaching-Learning-Based Optimization (TLBO) as new swarm
intelligent optimization algorithms have received much attention in recent years.
Both of them have shown outstanding performance for solving NP-Hard optimization
problems. However, they also suffer dramatic performance degradation for some
complex high-dimensional optimization problems. Through a lot of experiments, we
find that the HS and TLBO have strong complementarity each other. The HS has
strong global exploration power but low convergence speed. Reversely, the TLBO
has much fast convergence speed but it is easily trapped into local search. In
this work, we propose a hybrid search algorithm named HSTLBO that merges the two
algorithms together for synergistically solving complex optimization problems
using a self-adaptive selection strategy. In the HSTLBO, both HS and TLBO are
modified with the aim of balancing the global exploration and exploitation
abilities, where the HS aims mainly to explore the unknown regions and the TLBO
aims to rapidly exploit high-precision solutions in the known regions. Our
experimental results demonstrate better performance and faster speed than five
state-of-the-art HS variants and show better exploration power than five good
TLBO variants with similar run time, which illustrates that our method is
promising in solving complex high-dimensional optimization problems. The
experiment on portfolio optimization problems also demonstrate that the HSTLBO is
effective in solving complex read-world application.
PMID- 28403223
TI - Vascular endothelial growth factor A amplification in colorectal cancer is
associated with reduced M1 and M2 macrophages and diminished PD-1-expressing
lymphocytes.
AB - VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA
amplification, as well as by macrophages and lymphocytes in the tumor
microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD
1-positive lymphocytes and PD-L1 tumoral and stromal expression in colorectal
cancers harboring VEGFA amplification or chromosome 6 polysomy. 38 CRCs of which
13 harbored VEGFA amplification, 6 with Chr6 polysomy and 19 with neutral VEGFA
copy number were assessed by immunohistochemistry for CD68 (marker for M1/M2
macrophages), CD163 (M2 macrophages), programmed death 1(PD-1)- tumor
infiltrating and stromal lymphocytes as well as tumoral and stromal PD-1 ligand
(PD-L1) expression. CRCs with VEGFA amplification or Chr6 polysomy were
associated with decreased M1/M2 macrophages, reduced PD-1-expressing lymphocyte
infiltration, as well as reduced stromal expression of PD-L1 at the tumor front.
Compared to intermediate-grade CRCs, high-grade CRCs were associated with
increased M1/M2 macrophages and increased tumoral expression of PD-L1. Our
results suggest that VEGFA amplification or Chr6 polysomy is associated with an
altered tumor immune microenvironment.
PMID- 28403225
TI - Association of vitamin D deficiency, season of the year, and latent tuberculosis
infection among household contacts.
AB - OBJECTIVES: Vitamin D (VD) enhances the immune response against Mycobacterium
tuberculosis in vitro, and VD deficiency has been described in patients with
active tuberculosis (TB). However, the role of hypovitaminosis D in the
pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate
the association of VD deficiency, season of the year, and latent TB infection in
household contacts (HHC), given that this is a potentially modifiable condition
often related to nutritional deficiencies and lack of sun exposure. METHODS: We
prospectively enrolled new pulmonary TB cases (n = 107) and their HHC (n = 144)
over a 2-year period in Santiago, Chile. We compared plasma 25
hydroxycholecalciferol (25OHD) levels and examined the influence of season,
ethnic background, living conditions, and country of origin. RESULTS: Over 77% of
TB cases and 62.6% of HHC had VD deficiency (<20 ng/ml). Median 25OHD
concentration was significantly lower in TB cases than in HHC (11.7 vs. 18.2
ng/ml, p<0.0001). Migrants HHC had lower 25OHD levels than non-migrants (14.6 vs.
19.0 ng/ml, p = 0.026), and a trend towards a higher burden of latent TB
infection (52.9% vs. 35.2%, p = 0.066). Multivariate analysis found VD deficiency
in HHC was strongly associated with being sampled in winter/spring (adOR 25.68,
95%CI 7.35-89.7), corresponding to the seasons with lowest solar radiation
exposure. Spring enrollment-compared with other seasons-was the chief risk factor
for latent TB infection in HHC (adOR 3.14, 95%CI 1.28-7.69). CONCLUSIONS:
Hypovitaminosis D was highly prevalent in TB cases and also in HHC. A marked
seasonality was found for both VD levels and latent TB in HHC, with winter being
the season with lowest VD levels and spring the season with the highest risk of
latent TB infection.
PMID- 28403227
TI - Wolbachia density changes seasonally amongst populations of the pale grass blue
butterfly, Zizeeria maha (Lepidoptera: Lycaenidae).
AB - Previous studies showed that the survival rate of Wolbachia decreases under high
temperature in incubators. It is also known that a high density of Wolbachia in
the host body reduces the host emergence rate, while low densities fail to change
reproduction rates. However, few studies have examined the density of Wolbachia
in hosts in the field. Here, we focus on Wolbachia infection of the pale grass
blue butterfly, Zizeeria maha (Lepidoptera: Lycaenidae), which is distributed
throughout the Japanese islands. We examined the rate and density of Wolbachia
infection in the bodies of butterflies at thirteen locations in Japan. At seven
of these places, we collected butterflies in different seasons to determine
seasonal differences in the infection rate and density and found that Wolbachia
density has seasonal differences within the same population. Moreover, to
determine whether Wolbachia density has a geographical cline, we compared the
infection density of Wolbachia amongst all geographical populations. In addition,
we determined the sequences of Wolbachia wsp and host mtDNA CO1 haplotypes of all
populations. The results showed that Wolbachia density increased in early summer
and decreased in autumn. Further, the density of Wolbachia infecting the same
strain of Z. maha varied amongst populations, although no tendency in
geographical cline was observed.
PMID- 28403229
TI - Correction: Interferon beta-1a for the treatment of Ebola virus disease: A
historically controlled, single-arm proof-of-concept trial.
AB - [This corrects the article DOI: 10.1371/journal.pone.0169255.].
PMID- 28403226
TI - Function of translationally controlled tumor protein (TCTP) in Eudrilus eugeniae
regeneration.
AB - TCTP (Translationally Controlled Tumour Protein) is a multifunctional protein
that plays a role in the development, immune system, tumour reversion, and
maintenance of stem cells. The mRNA of the Tpt1 gene is over-expressed during
liver regeneration. But, the function of the protein in regeneration is not
known. To study the role of the protein in regeneration, the earthworm Eudrilus
eugeniae was chosen. First, the full length cDNA of the Tpt1 gene was sequenced.
The size of the cDNA is 504 bp and the protein has 167 amino acids. The highest
level of TCTP expression was documented in the worm after three days of
regeneration. The protein was found to be expressed specifically in the
epithelial layer of the skin. During regeneration, the protein expression was
found to be the highest at the tip of blastema. The pharmacological suppression
of TCTP using nutlin-3 and TCTP RNAi experiments resulted in the failure of the
regeneration process. The suppression of TCTP caused the arrest of proliferation
in posterior amputated worms. The severe cell death was documented in the
amputated region of nutlin-3 injected worm. The silencing of TCTP has blocked the
modification of clitellar segments. The experiments confirm that TCTP has major
functions in the upstream signalling of cell proliferation in the early
regeneration process in E. eugeniae.
PMID- 28403228
TI - Refining particle positions using circular symmetry.
AB - Particle and object tracking is gaining attention in industrial applications and
is commonly applied in: colloidal, biophysical, ecological, and micro-fluidic
research. Reliable tracking information is heavily dependent on the system under
study and algorithms that correctly determine particle position between images.
However, in a real environmental context with the presence of noise including
particular or dissolved matter in water, and low and fluctuating light
conditions, many algorithms fail to obtain reliable information. We propose a new
algorithm, the Circular Symmetry algorithm (C-Sym), for detecting the position of
a circular particle with high accuracy and precision in noisy conditions. The
algorithm takes advantage of the spatial symmetry of the particle allowing for
subpixel accuracy. We compare the proposed algorithm with four different methods
using both synthetic and experimental datasets. The results show that C-Sym is
the most accurate and precise algorithm when tracking micro-particles in all
tested conditions and it has the potential for use in applications including
tracking biota in their environment.
PMID- 28403230
TI - Isoflurane anesthesia promotes cognitive impairment by inducing expression of
beta-amyloid protein-related factors in the hippocampus of aged rats.
AB - Isoflurane anesthesia has been shown to be responsible for cognitive impairment
in Alzheimer's disease (AD) and development of AD in the older age groups.
However, the pathogenesis of AD-related cognitive impairments induced by
isoflurane anesthesia remains elusive. Thus, this study was designed to
investigate the mechanism by which isoflurane anesthesia caused AD-related
cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n =
12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO
0.5D, ISO 1D, ISO 3D and ISO 7D). The CONT group inhaled 30% O2 for 2 h without
any anesthesia. ISO groups were placed under anesthesia with 3% isoflurane and
then exposed to 1.5% isoflurane delivered in 30% O2 for 2 h. Rats in each ISO
group were then analyzed immediately (ISO 0) or at various time points (0.5, 1, 3
or 7 day) after this exposure. Cognitive function was assessed using the Morris
water maze test. Protein levels of amyloid precursor protein (APP), beta-site APP
cleavage enzyme-1 (BACE-1) and Abeta42 peptide were analyzed in hippocampal
samples by Western blot. beta-Amyloid (Abeta) plaques were detected in
hippocampal sections by Congo red staining. Compared with controls, all ISO
groups showed increased escape latency and impaired spatial memory. Isoflurane
increased APP mRNA expression and APP protein depletion, promoting Abeta42
overproduction, oligomerization and accumulation. However, isoflurane did not
affect BACE-1 expression. Abeta plaques were observed only in those ISO groups
sacrificed at 3 or 7 d. Our data indicate that aged rats exposed to isoflurane
had increased APP mRNA expression and APP protein depletion, with Abeta42 peptide
overproduction and oligomerization, resulting in formation of Abeta plaques in
the hippocampus. Such effects might have contributed to cognitive impairments,
including in spatial memory, observed in these rats after isoflurane anesthesia.
PMID- 28403231
TI - Media effects on suicide methods: A case study on Hong Kong 1998-2005.
AB - BACKGROUND: Previous studies have suggested that mass media's reports of new
suicide methods will increase suicides using the same method. The same pattern
seems not to apply to a conventional suicide method, unless it was used by a
celebrity. OBJECTIVE: 1) to examine media effects on both new and non-new suicide
methods during 1998 and 2005 in Hong Kong (HK), when a new method by burning
charcoal (CB suicide) was spreading in the region. 2) to examine how CB competed
with non-CB methods in terms of media coverage and "recruiting" suicidal persons
in the socio-economic context. METHODS: A self- and mutual- exciting process
model was fitted to the data, adjusting for divorce rate, unemployment rate, and
property price index. Breaking the whole period into onset, peak, and post-peak
stages, the model was fitted again to examine the differences. RESULTS:
Comparable copycat effects were found on both CB and non-CB suicide news. The
only cross-method media effects were found in the onset stage when non-CB suicide
news showed suppressing effect on CB suicides. CB suicides reported a significant
self-excitation effect. A higher divorce rate and lower property price index were
associated with significantly more suicides incidences and more suicide news.
CONCLUSIONS: The emerging of CB suicide method did not substitute media coverage
of non-CB suicide in HK. Media effects in this case were not limited to new
suicide method or celebrity suicide. The effects were further fueled by adverse
socio-economic conditions.
PMID- 28403232
TI - An oil containing EPA and DHA from transgenic Camelina sativa to replace marine
fish oil in feeds for Atlantic salmon (Salmo salar L.): Effects on intestinal
transcriptome, histology, tissue fatty acid profiles and plasma biochemistry.
AB - New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC
PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain
adequate levels of the beneficial fatty acids, eicosapentaenoic and
docosahexaenoic (EPA and DHA, respectively). The present study investigated the
use of an EPA+DHA oil derived from transgenic Camelina sativa in Atlantic salmon
(Salmo salar) feeds containing low levels of fishmeal (35%) and fish oil (10%),
reflecting current commercial formulations, to determine the impacts on tissue
fatty acid profile, intestinal transcriptome, and health of farmed salmon. Post
smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets
containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil
(WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did
not affect any of the fish performance or health parameters studied. Analyses of
the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh
of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than
fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds
offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels
comparable to those found a decade ago.
PMID- 28403233
TI - Cost-effectiveness of cetuximab and panitumumab for chemotherapy-refractory
metastatic colorectal cancer.
AB - BACKGROUND: Cetuximab and panitumumab are monoclonal antibodies targeting the
epidermal growth factor receptor. Both drugs are active against RAS wild type
metastatic colorectal cancer after chemotherapy failure, with similar efficacy
and toxicity profiles. However, their cost and limited survival benefits may
compromise incorporation in the Brazilian public healthcare system, the Unified
Heath System (Sistema Unico de Saude) (SUS). METHODS: A cost-effectiveness
analysis was conducted using a Markov model from the Brazilian Public health
perspective and a lifetime horizon in patients with RAS -wt mCRC. Transition
probabilities and mortality rates were extracted from randomized studies.
Treatment costs were obtained from price tables regulated by the Brazilian Health
Ministry. The World Health Organization recommendation of three times GDP per
capita was used to define the cost-effectiveness threshold. RESULTS: The use of
cetuximab or panitumumab for chemotherapy-refractory mCRC patients resulted in
0.22 additional life-years relative to BSC, with incremental cost-effectiveness
ratios (ICERs) of $58,240 and $52,772 per LY, respectively. That exceeds the pre
specified threshold for cost-effectiveness. Acquisition of biological agents was
the major driver of increased costs. CONCLUSIONS: Our economic evaluation
demonstrates that both cetuximab and panitumumab are not a cost-effective
approach in RAS-wt mCRC patients. Discussion about drug price should be
prioritized to enable incorporation of these monoclonal antibodies in the SUS.
PMID- 28403235
TI - Correction: Altered regulation and expression of genes by BET family of proteins
in COPD patients.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173115.].
PMID- 28403234
TI - Transcriptional repression of frequency by the IEC-1-INO80 complex is required
for normal Neurospora circadian clock function.
AB - Rhythmic activation and repression of the frequency (frq) gene are essential for
normal function of the Neurospora circadian clock. WHITE COLLAR (WC) complex, the
positive element of the Neurospora circadian system, is responsible for
stimulation of frq transcription. We report that a C2H2 finger domain-containing
protein IEC-1 and its associated chromatin remodeling complex INO80 play
important roles in normal Neurospora circadian clock function. In iec-1KO
strains, circadian rhythms are abolished, and the frq transcript levels are
increased compared to that of the wild-type strain. Similar results are observed
in mutant strains of the INO80 subunits. Furthermore, ChIP data show that
recruitment of the INO80 complex to the frq promoter is IEC-1-dependent. WC
mediated transcription of frq contributes to the rhythmic binding of the INO80
complex at the frq promoter. As demonstrated by ChIP analysis, the INO80 complex
is required for the re-establishment of the dense chromatin environment at the
frq promoter. In addition, WC-independent frq transcription is present in ino80
mutants. Altogether, our data indicate that the INO80 complex suppresses frq
transcription by re-assembling the suppressive mechanisms at the frq promoter
after transcription of frq.
PMID- 28403236
TI - Correction: Long-Term Stable and Tightly Controlled Expression of Recombinant
Proteins in Antibiotics-Free Conditions.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166890.].
PMID- 28403238
TI - Mobile Genome Express (MGE): A comprehensive automatic genetic analyses pipeline
with a mobile device.
AB - The development of next-generation sequencing (NGS) technology allows to sequence
whole exomes or genome. However, data analysis is still the biggest bottleneck
for its wide implementation. Most laboratories still depend on manual procedures
for data handling and analyses, which translates into a delay and decreased
efficiency in the delivery of NGS results to doctors and patients. Thus, there is
high demand for developing an automatic and an easy-to-use NGS data analyses
system. We developed comprehensive, automatic genetic analyses controller named
Mobile Genome Express (MGE) that works in smartphones or other mobile devices.
MGE can handle all the steps for genetic analyses, such as: sample information
submission, sequencing run quality check from the sequencer, secured data
transfer and results review. We sequenced an Actrometrix control DNA containing
multiple proven human mutations using a targeted sequencing panel, and the whole
analysis was managed by MGE, and its data reviewing program called ELECTRO. All
steps were processed automatically except for the final sequencing review
procedure with ELECTRO to confirm mutations. The data analysis process was
completed within several hours. We confirmed the mutations that we have
identified were consistent with our previous results obtained by using multi
step, manual pipelines.
PMID- 28403237
TI - Evidence of neurofibromatosis type 1 in a multi-morbid Inca child mummy: A
paleoradiological investigation using computed tomography.
AB - OBJECTIVE: In this study, an Inca bundle was examined using computed tomography
(CT). The primary aim was to determine the preservation status of bony and soft
tissues, the sex, the age at the time of death, possible indicators for disease
or even the cause of death, as well as the kind of mummification. A secondary aim
was to obtain a brief overview of the wrapping in order to gain additional
information on the cultural background. MATERIALS AND METHODS: The bundle belongs
to the Museum of Cultures in Basel, Switzerland, and was bought in Munich,
Germany, in 1921. Radiocarbon dating of the superficial textile yielded a
calibrated age between 1480 and 1650 AD. The mummy was investigated using multi
slice CT with slice thickness of 0.75 mm and 110 kilovolt. For standardized
assessment of soft tissue preservation, a recently developed checklist was
applied. RESULTS: CT revealed the mummy of a seven to nine year old boy with
superior preservation of bony and soft tissues allowing detailed assessment.
Indicators of neurofibromatosis type 1 (paravertebral and cutaneous
neurofibromas, a breast neurofibroma, sphenoid wing dysplasia), Chagas disease
(dilatation of the esophagus, stomach, rectum, and large amounts of feces), and
lung infection (pleural adherence, calcifications), probably due to tuberculosis,
were found. Furthermore, signs of peri-mortem violence (transection of the chest
and a defect in the abdominal wall) were detected. CT images revealed a carefully
performed wrapping. CONCLUSION: CT examination of the Inca bundle proved to be an
important non-destructive examination method. Standardized assessment, especially
of the soft tissue structures, allowed for diagnoses of several diseases,
indicating a multi-morbid child at the time of death. The careful wrapping
pointed to a ceremonial burial. Within the cultural background, the signs of
fatal violence were discussed as a possible result of war, murder, accident, or
human sacrifice.
PMID- 28403239
TI - Simulated blast overpressure induces specific astrocyte injury in an ex vivo
brain slice model.
AB - Exposure to explosive blasts can produce functional debilitation in the absence
of brain pathology detectable at the scale of current diagnostic imaging.
Transient (ms) overpressure components of the primary blast wave are considered
to be potentially damaging to the brain. Astrocytes participate in neuronal
metabolic maintenance, blood-brain barrier, regulation of homeostatic
environment, and tissue remodeling. Damage to astrocytes via direct physical
forces has the potential to disrupt local and global functioning of neuronal
tissue. Using an ex vivo brain slice model, we tested the hypothesis that viable
astrocytes within the slice could be injured simply by transit of a single blast
wave consisting of overpressure alone. A polymer split Hopkinson pressure bar
(PSHPB) system was adapted to impart a single positive pressure transient with a
comparable magnitude to those that might be present inside the head. A custom
built test chamber housing the brain tissue slice incorporated revised design
elements to reduce fluid space and promote transit of a uniform planar waveform.
Confocal microscopy, stereology, and morphometry of glial fibrillary acidic
protein (GFAP) immunoreactivity revealed that two distinct astrocyte injury
profiles were identified across a 4 hr post-test survival interval: (a) presumed
conventional astrogliosis characterized by enhanced GFAP immunofluorescence
intensity without significant change in tissue area fraction and (b) a process
comparable to clasmatodendrosis, an autophagic degradation of distal processes
that has not been previously associated with blast induced neurotrauma. Analysis
of astrocyte branching revealed early, sustained, and progressive differences
distinct from the effects of slice incubation absent overpressure testing.
Astrocyte vulnerability to overpressure transients indicates a potential for
significant involvement in brain blast pathology and emergent dysfunction. The
testing platform can isolate overpressure injury phenomena to provide novel
insight on physical and biological mechanisms.
PMID- 28403240
TI - SnoVault and encodeD: A novel object-based storage system and applications to
ENCODE metadata.
AB - The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative
effort to create a comprehensive catalog of functional elements initiated shortly
after the completion of the Human Genome Project. The current database exceeds
6500 experiments across more than 450 cell lines and tissues using a wide array
of experimental techniques to study the chromatin structure, regulatory and
transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE
experimental data, metadata, and associated computational analyses are submitted
to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage,
unified processing, and distribution to community resources and the scientific
community. As the volume of data increases, the identification and organization
of experimental details becomes increasingly intricate and demands careful
curation. The ENCODE DCC has created a general purpose software system, known as
SnoVault, that supports metadata and file submission, a database used for
metadata storage, web pages for displaying the metadata and a robust API for
querying the metadata. The software is fully open-source, code and installation
instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the
generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data
in the manner of ENCODE. The core database engine, SnoVault (which is completely
independent of ENCODE, genomic data, or bioinformatic data) has been released as
a separate Python package.
PMID- 28403241
TI - Characterization of a novel HIV-1 unique recombinant form between CRF07_BC and
CRF55_01B in men who have sex with men in Guangzhou, China.
AB - Here, we report the genetic diversity of HIV-1 and emergence of novel HIV-1
unique recombinant forms (URF) in both HIV-infected intravenous drug users (IDU)
and men who have sex with men (MSM) in Guangzhou, China. We further characterized
a novel URF strain isolated from an HIV-infected MSM, GD698. Near full-length
genome (NFLG) phylogenic analysis showed that this novel URF was composed of
CRF07_BC and CRF55_01B, with two recombinant breakpoints (nt 6,003 and 8,251
relative to the HXB2 genome) in the vpu/env and env genes, respectively. Twenty
six percent of the genome is classified as CRF55_01B, spanning part of vpu and
most of the env gene. The remaining 74% of the genome is classified as CRF07_BC.
Both the backbone CRF07_BC sequence and CRF55_01B fragment were clustered with
the HIV-1 isolates found in MSM. The emergence of the novel HIV-1 recombinant
indicates the ongoing recombinants derived from the CRF07_BC and CRF55_01B
isolates, and provides critical insights into our understanding of the dynamics
and complexity of the HIV-1 epidemic in China.
PMID- 28403242
TI - Brain metabolomic profiling of eastern honey bee (Apis cerana) infested with the
mite Varroa destructor.
AB - The mite Varroa destructor is currently the greatest threat to apiculture as it
is causing a global decrease in honey bee colonies. However, it rarely causes
serious damage to its native hosts, the eastern honey bees Apis cerana. To better
understand the mechanism of resistance of A. cerana against the V. destructor
mite, we profiled the metabolic changes that occur in the honey bee brain during
V. destructor infestation. Brain samples were collected from infested and control
honey bees and then measured using an untargeted liquid chromatography-tandem
mass spectrometry (LC-MS/MS)-based global metabolomics method, in which 7918 and
7462 ions in ESI+ and ESI- mode, respectively, were successfully identified.
Multivariate statistical analyses were applied, and 64 dysregulated metabolites,
including fatty acids, amino acids, carboxylic acid, and phospholipids, amongst
others, were identified. Pathway analysis further revealed that linoleic acid
metabolism; propanoate metabolism; and glycine, serine, and threonine metabolism
were acutely perturbed. The data obtained in this study offer insight into the
defense mechanisms of A. cerana against V. destructor mites and provide a better
method for understanding the synergistic effects of parasitism on honey bee
colonies.
PMID- 28403243
TI - Within-season variability of fighting behaviour in an Australian alpine
grasshopper.
AB - Throughout the breeding season, changing environmental and biological conditions
can lead to variation in the reproductive landscape of many species. In alpine
environments temperature is a key driver of behaviour for small ectotherms such
as insects, but variable biotic factors such as mate quality and availability can
also influence behaviour. Kosicuscola tristis is a small semelparous grasshopper
of the Australian alpine region. In a rare behaviour among grasshoppers, K.
tristis males engage in vigorous fights over access to females, involving
mandible displays, kicking, biting and grappling. In this study we describe the
variation in fighting behaviour of K. tristis throughout the breeding season and
test several hypotheses related to temperature, body size, mating behaviour, and
female quality. We show that K. tristis males are more aggressive toward each
other at the end of the breeding season than at the beginning. This increased
aggression is associated with decreased daily average temperatures (from ~20
degrees C to ~9 degrees C), decreased mating activity, increased female
fecundity, and an unexpected trend toward an increase in female-to-male
aggression. These results suggest that K. tristis is likely under increased
selective pressure to time key life cycle events with favourable biological and
climatic conditions. The stochastic nature of alpine environments combined with a
relatively short life span and breeding season, as well as limited mating
opportunities toward the end of the season may have contributed to the evolution
of this extraordinary mating system.
PMID- 28403244
TI - Wild inside: Urban wild boar select natural, not anthropogenic food resources.
AB - Most wildlife species are urban avoiders, but some became urban utilizers and
dwellers successfully living in cities. Often, they are assumed to be attracted
into urban areas by easily accessible and highly energetic anthropogenic food
sources. We macroscopically analysed stomachs of 247 wild boar (Sus scrofa,
hereafter WB) from urban areas of Berlin and from the surrounding rural areas.
From the stomach contents we determined as predictors of food quality modulus of
fineness (MOF,), percentage of acid insoluble ash (AIA) and macronutrients such
as amount of energy and percentage of protein, fat, fibre and starch. We run
linear mixed models to test: (1) differences in the proportion of landscape
variables, (2) differences of nutrients consumed in urban vs. rural WB and (3)
the impact of landscape variables on gathered nutrients. We found only few cases
of anthropogenic food in the qualitative macroscopic analysis. We categorized the
WB into five stomach content categories but found no significant difference in
the frequency of those categories between urban and rural WB. The amount of
energy was higher in stomachs of urban WB than in rural WB. The analysis of
landscape variables revealed that the energy of urban WB increased with
increasing percentage of sealing, while an increased human density resulted in
poor food quality for urban and rural WB. Although the percentage of protein
decreased in areas with a high percentage of coniferous forests, the food quality
increased. High percentage of grassland decreased the percentage of consumed fat
and starch and increased the percentage of fibre, while a high percentage of
agricultural areas increased the percentage of consumed starch. Anthropogenic
food such as garbage might serve as fallback food when access to natural
resources is limited. We infer that urban WB forage abundant, natural resources
in urban areas. Urban WB might use anthropogenic resources (e.g. garbage) if
those are easier to exploit and more abundant than natural resources. This study
shows that access to natural resources still is mandatory and drives the amount
of protein, starch, fat or fibre in wild boar stomachs in urban as well as rural
environments.
PMID- 28403245
TI - Author-paper affiliation network architecture influences the methodological
quality of systematic reviews and meta-analyses of psoriasis.
AB - Moderate-to-severe psoriasis is associated with significant comorbidity, an
impaired quality of life, and increased medical costs, including those associated
with treatments. Systematic reviews (SRs) and meta-analyses (MAs) of randomized
clinical trials are considered two of the best approaches to the summarization of
high-quality evidence. However, methodological bias can reduce the validity of
conclusions from these types of studies and subsequently impair the quality of
decision making. As co-authorship is among the most well-documented forms of
research collaboration, the present study aimed to explore whether authors'
collaboration methods might influence the methodological quality of SRs and MAs
of psoriasis. Methodological quality was assessed by two raters who extracted
information from full articles. After calculating total and per-item Assessment
of Multiple Systematic Reviews (AMSTAR) scores, reviews were classified as low (0
4), medium (5-8), or high (9-11) quality. Article metadata and journal-related
bibliometric indices were also obtained. A total of 741 authors from 520
different institutions and 32 countries published 220 reviews that were
classified as high (17.2%), moderate (55%), or low (27.7%) methodological
quality. The high methodological quality subnetwork was larger but had a lower
connection density than the low and moderate methodological quality subnetworks;
specifically, the former contained relatively fewer nodes (authors and reviews),
reviews by authors, and collaborators per author. Furthermore, the high
methodological quality subnetwork was highly compartmentalized, with several
modules representing few poorly interconnected communities. In conclusion,
structural differences in author-paper affiliation network may influence the
methodological quality of SRs and MAs on psoriasis. As the author-paper
affiliation network structure affects study quality in this research field,
authors who maintain an appropriate balance between scientific quality and
productivity are more likely to develop higher quality reviews.
PMID- 28403246
TI - Retraction: Rtt107 Phosphorylation Promotes Localisation to DNA Double-Stranded
Breaks (DSBs) and Recombinational Repair between Sister Chromatids.
PMID- 28403248
TI - Effect of Buccal Implant Inclination on Stresses Around Two-Implant-Retained
Overdentures with Resilient Stud Attachments.
AB - PURPOSE: This study aimed to evaluate the effect of buccal implant inclination on
stresses around two-implant-retained overdentures with resilient stud
attachments. MATERIALS AND METHODS: Four acrylic models representing a mandibular
edentulous ridge were constructed. For each model, two implants were placed at
canine areas. Models were classified into four types according to the degree of
buccal implant inclination: Group I (GI, 0 degrees), Group II (GII, 10 degrees),
Group III (GIII, 20 degrees), and Group IV (GIV, 30 degrees). Overdentures were
connected to the implants with Locator attachments. Regular light-retention
inserts were used for all groups, and extended range inserts were also used for
GIV (GIVext), making a fifth comparison group. Four strain gauges were bonded at
the buccal, lingual, mesial, and distal surfaces of each implant to monitor the
stresses during bilateral and unilateral load application. RESULTS: Tensile
stresses were recorded at distal and lingual gauges, and compressive stresses
were recorded at mesial and buccal gauges for all groups. GIV recorded the
highest stresses, followed by GIII, GII, GIVext, and GI. Distal position recorded
the highest stresses, followed by lingual, mesial, and buccal. Nonloading side
was associated with significantly higher stresses than loading side. CONCLUSION:
The peri-implant stresses increase as the buccal implant inclination increases
when resilient stud attachments are used for implant overdentures. Therefore, it
is recommended to insert the implants parallel to each other to decrease peri
implant stresses. However, when buccal inclination is inevitable due to
anatomical limitations, it should be limited to 10 degrees for standard nylon
inserts, or extended range inserts are recommended.
PMID- 28403247
TI - Early Complications of Immediate Loading in Edentulous Full-Arch Restorations: A
Retrospective Analysis of 88 Cases.
AB - PURPOSE: To describe the clinical outcomes and complications related to
provisional prostheses after full-arch implant-supported rehabilitation by means
of an immediate loading protocol. MATERIALS AND METHODS: This retrospective
cohort study included patients who were consecutively treated with full-arch
implant-supported restorations with a minimum of four implants (Replace Select
Tapered TiUnite, Nobel Biocare AB) per arch and conical abutments (multi-unit,
Nobel Biocare AB) by means of an immediate loading protocol. The surgical
procedures were performed between May 2006 and June 2014 by a single oral
surgeon. Demographic, surgical, and prosthetic variables were collected, and
biologic and mechanical complications were registered. RESULTS: A total of 61
maxillae (57%) and 46 mandibles (43%) were treated in 88 patients (40 men and 48
women) with a mean age of 62.4 years. A total of 558 implants were placed, 295 in
postextraction sockets. A total of 331 implants (59.3%) were placed in the
maxilla and 227 (40.7%) in the mandible. Within a 9-month period, 18 prostheses
(16.8%) fractured (15 maxillary and 3 mandibular); in nine of these patients the
opposing dentition was a full-arch, implant-supported restoration, and in the
remaining nine patients, it was natural dentition. Six (1.1%) maxillary and three
(0.5%) mandibular implants failed. CONCLUSIONS: A high implant survival rate is
expected in the short term following this immediate loading protocol. Fracture of
the provisional prosthesis is a common finding, affecting 17% of patients, and is
significantly more prevalent in patients with bruxism and in maxillary
prostheses.
PMID- 28403249
TI - Accuracy of Cone Beam Computed Tomography Grayscale Density in Determining Bone
Architecture in the Posterior Mandible: An In Vivo Study with Microcomputed
Tomography Validation.
AB - PURPOSE: The aim of this study was to analyze the reliability of cone beam
computed tomography (CBCT) in assessing the grayscale density (GSD) of bone by
comparing it with microcomputed tomography (MU-CT) data. MATERIALS AND METHODS: A
total of 50 subjects with lost mandibular molars were included in the study. To
assess the bone GSD, a previously fabricated template made of acrylic resin with
a 2-mm-diameter metal rod was positioned, and CBCT was performed. The bone
biopsies for MU-CT analysis were then obtained during implant surgery. The
relationship between GSD assessed by CBCT and data from MU-CT analysis was
studied using Spearman's rank correlation. RESULTS: A total of 38 biopsies were
available for MU-CT analysis. Positive correlations were identified between GSD
and bone volumetric fraction (BV/TV) (r = 0.835, P < .001), bone volume (BV) (r =
0.353, P = .030), trabecular spacing (Tb.Sp) (r = -0.535, P = .001), and mean
total volume (TV) (r = 0.470, P = .003). There was a clear positive linear
correlation between normal values of GSD (< 700) and BV (r = 0.545). CONCLUSION:
This study demonstrated the correlation between GSD assessed by CBCT and bone
density assessed by MU-CT in the posterior mandible. For areas of typical bone
density, there seems to be a positive linear correlation between GSD assessed by
CBCT and bone density assessed by MU-CT.
PMID- 28403262
TI - Combination of In-Office Chemical Peels With a Topical Comprehensive Pigmentation
Control Product in Skin of Color Subjects With Facial Hyperpigmentation.
AB - Dyschromia is one of the primary complaints for patients with skin of color.
Treatments need to achieve a balance between tolerability and efficacy to address
existing hyperpigmentation without causing additional damage that could trigger
post-inflammatory hyperpigmentation (PIH). An open-label, single-center study was
conducted to assess the efficacy of a novel comprehensive pigmentation control
serum (LYT2) combined with a series of three very superficial chemical peels (VP)
in skin of color subjects. Seventeen female and male subjects aged 36 to 69 years
with Fitzpatrick Skin Types III-VI and moderate to severe facial
hyperpigmentation were enrolled in the 12-week clinical study. Subjects
identified as Asian, Hispanic, African American, or Caucasian ethnicities.
Subjects received a series of 3 VP treatments every 4 weeks. LYT2 was applied
twice-daily in between VP treatments. Investigator assessments for overall
hyperpigmentation, overall photodamage, and skin tone unevenness, as well as
standardized digital photography and subject self-assessment questionnaires were
conducted at all visits (baseline and weeks 4, 8, and 12). In vivo reflectance
confocal microscopy (RCM) of a target lesion was conducted (in a subset of
subjects) at baseline and week 12. Fourteen subjects completed the study. The
treatment regimen provided statistically significant improvements in all efficacy
parameters at weeks 8 and 12 (all P less than equal to 0.03, student's t-test).
Standardized digital photography and RCM images support the improvements in
overall hyperpigmentation observed by the investigator. At the end of treatment,
the regimen was highly rated by subjects with 100% of subjects (strongly
agree/agree) that the combination "decreased the appearance of uneven skin tone
and discolorations" and "reduced the appearance of sun damage." In addition to
this clinical study, independent case studies with this combination treatment
regimen at a separate study site were also conducted with results that
corroborate the formal clinical study findings. The comprehensive results from
these studies suggest that the combination of a comprehensive pigmentation
control serum with a series of 3 very superficial chemical peels may provide an
effective treatment approach for hyperpigmentation in skin of color patients.
J Drugs Dermatol. 2017;16(4):301-306.
.
PMID- 28403263
TI - Microneedling in All Skin Types: A Review.
AB - INTRODUCTION: Microneedling procedures are growing in popularity for a wide
variety of skin conditions. This paper comprehensively reviews the medical
literature regarding skin needling efficacy and safety in all skin types and in
multiple dermatologic conditions.
METHODS: A PubMed literature search was
conducted in all languages without restriction and bibliographies of relevant
articles reviewed. Search terms included: "microneedling," "percutaneous collagen
induction," "needling," "skin needling," and "dermaroller."
RESULTS:
Microneedling is most commonly used for acne scars and cosmetic rejuvenation,
however, treatment benefit has also been seen in varicella scars, burn scars,
keloids, acne, alopecia, and periorbital melanosis, and has improved flap and
graft survival, and enhanced transdermal delivery of topical products. Side
effects were mild and self-limited, with few reports of post-inflammatory
hyperpigmentation, and isolated reports of tram tracking, facial allergic
granuloma, and systemic hypersensitivity.
DISCUSS: Microneedling
represents a safe, cost-effective, and efficacious treatment option for a variety
of dermatologic conditions in all skin types. More double-blinded, randomized,
controlled trials are required to make more definitive conclusions.
J
Drugs Dermatol. 2017;16(4):308-314.
.
PMID- 28403264
TI - A Retrospective Review of Treatment Results for Patients With Central Centrifugal
Cicatrical Alopecia.
AB - INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of
scarring alopecia primarily affecting women of African descent on the crown of
the scalp. Limited data exists regarding evidence-based treatment for CCCA.
OBJECTIVE: To examine photos of subjects with CCCA before and after treatment
in order to evaluate results of treatment and compare results of different
treatment regimens.
METHODS: Photographs of 15 subjects with CCCA before
and after treatment were evaluated by two blinded investigators who assigned
disease severity scores to photographs based on a published scale: Central Scalp
Alopecia Photographic Scale in African American Women.
RESUTLS: Median
change in severity score (post-treatment severity score - pre-treatment severity
score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8
intralesional steroid injections along with topical steroids (Class I/II) +/-
minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after
treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P
= 0.38) and subjects receiving anti-dandruff shampoo versus those who did not
(0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in
pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had
decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15
(13.3%) had no change in severity scores.
CONCLUSIONS: Although no
statistically significant difference was found in pre- versus post-treatment
disease severity, this may indicate intralesional steroid injections and topical
steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease
progression.
J Drugs Dermatol. 2017;16(4):317-320.
.
PMID- 28403265
TI - Improvement of Atrophic Acne Scars in Skin of Color Using Topical Synthetic
Epidermal Growth Factor (EGF) Serum: A Pilot Study.
AB - BACKGROUND: Atrophic scarring in skin of color is a common, permanent, and
distressing result of uncontrolled acne vulgaris. Ablative lasers and chemical
peels are frequently used to improve the appearance of atrophic scars, primarily
through the stimulation of collagen and elastin; however, these treatment
modalities are associated with risks, such as dyspigmentation and hypertrophic
scarring, especially in patients with darker skin.
OBJECTIVE: We evaluated
the efficacy of topically applied synthetic epidermal growth factor (EGF) serum
in reducing the appearance of atrophic acne scars in skin of color.
METHODS: A single-center clinical trial was performed on twelve healthy men
and women (average age 32.5) with Fitzpatrick Type IV-V skin and evidence of
facial grade II-IV atrophic acne scars. Subjects applied topical EGF serum to the
full-face twice daily for 12 weeks. Scar improvement was investigated at each
visit using an Investigator Global Assessment (IGA), a Goodman grade, clinical
photography, and patient self-assessment.
RESULTS: Eleven subjects
completed the trial. Compared to baseline, there was an improvement in mean IGA
score from 3.36 (SEM = 0.15) to 2.18 (SEM = 0.33). Mean Goodman grade was reduced
from 2.73 (SEM = 0.19) to 2.55 (SEM = 0.21). Of the eleven pairs of before and
after photographs, nine were correctly chosen as the post-treatment image by a
blind investigator. On self-assessment, 81% reported a "good" to "excellent"
improvement in their scars compared to baseline (P = 0.004).
CONCLUSION:
Topical EGF may improve the appearance of atrophic acne scars in skin of color.
Additional, larger studies should be conducted to better characterize
improvement.
J Drugs Dermatol. 2017;16(4):322-326.
.
PMID- 28403266
TI - Laser-Assisted Photodynamic Therapy: Two Novel Protocols for Enhanced Treatment
Results.
AB - Photodynamic therapy (PDT) uses a topical photosensitizing agent which is
activated by a light source to cause destruction of specific cells. Commonly used
for the treatment of actinic keratoses and photodamage, PDT can also be used for
other conditions including acne and sebaceous hyperplasia. Here we report our
experience with two treatment protocols. The first protocol utilizes laser
assisted delivery of topical 5-aminolevulinic acid for enhanced efficacy of blue
light photodynamic therapy in the treatment of actinic keratoses and photodamage.
The second protocol utilizes red light photodynamic therapy followed by pulsed
dye laser to effectively target sebaceous glands in patients with extensive
sebaceous hyperplasia.
J Drugs Dermatol. 2017;16(4):329-331.
.
PMID- 28403267
TI - The Current State of Dermatologists' Familiarity and Perspectives of Biosimilars
for the Treatment of Psoriasis: A Global Cross-Sectional Survey.
AB - BACKGROUND: Biologic patent expiration, accelerated approval pathways, and
business interests of third party payers and the biopharmaceutical industry are
driving the development of biosimilars to treat immune-mediated disorders like
psoriasis. No studies have investigated dermatologists' familiarity and
perspectives of biosimilars.
OBJECTIVES: To assess: (1) dermatologists'
familiarity with biosimilars and interchangeability and (2) their perspectives
toward biosimilar properties, including interchangeability, indication
extrapolation, and immunogenicity risk.
METHODS: For this prospective
survey study, we distributed electronic and paper questionnaires to
dermatologists from selected societies and attendees at the 73rd annual American
Academy of Dermatology meeting between March 20, 2015 and May 30, 2015. Primary
outcome was dermatologists' familiarity with biosimilars. Secondary aims included
dermatologists' confidence in biosimilar efficacy and safety, familiarity
concerning the concept of interchangeability and perspectives regarding
indication extrapolation, interchangeability, and immunogenicity risk.
RESULTS: Of the 116 total dermatologists who completed the questionnaire, 73
(62.9%) were slightly to very unfamiliar with biosimilars. On a 5-point Likert
scale, dermatologists were somewhat to very concerned with the practice of
interchangeability (3.4+/-1.1) and slightly uncomfortable to fairly comfortable
in prescribing biosimilars for an extrapolated indication (3.3+/-1.0).
CONCLSUIONS: Our survey identified that the majority of dermatologists were
unfamiliar with biosimilars. Dermatologists were consistently concerned regarding
safety issues surrounding the practice of interchangeability without provider
knowledge.
J Drugs Dermatol. 2017;16(4):336-343.
.
PMID- 28403268
TI - Quality of Life in a Vitiligo Support Group.
AB - : BACKGROUND: No study has examined the impact of vitiligo support group
membership on vitiligo patient quality of life (QoL).
OBJECTIVE: We sought
to examine the QoL impact of vitiligo support groups by comparing QoL and
associated patient characteristics between vitiligo patients who are and are not
members of a vitiligo support group.
METHODS: Members of a Henry Ford
Hospital-sponsored, Southeast Michigan Vitiligo Support Group were compared to
non-member vitiligo patients recruited from a previous study cohort.17 Eligible
patients were asked to complete the Dermatology Life Quality Index (DLQI) and a
study-specific questionnaire designed to collect relevant patient
characteristics.
RESULTS: The mean DLQI scores for the support group
members and non-members were similar (7.1 +/- 5.4 and 6.0 +/- 6.5, respectively;
P-value 0.2), despite the support group members reporting more severe overall
disease and increased disease severity in exposed portions of the body. The
African-American: Caucasian ratio and the prevalence of unemployment were both
significantly higher among the support group participants. LIMITATIONS: Small
sample size may have limited the study's ability to demonstrate the differences
between the support group participants and the controls.
CONCLUSIONS: The
similar QoL despite an increased prevalence of poorer QoL indicators among the
support group participants suggests a protective effect of support group
membership.
J Drugs Dermatol. 2017;16(4):344-350.
.
PMID- 28403269
TI - Mid-Face Volumization With Hyaluronic Acid: Injection Technique and Safety
Aspects from a Controlled, Randomized, Double-Blind Clinical Study.
AB - : BACKGROUND: Injection of hyaluronic acid (HA) volumizing fillers in the
malar area is intended for rejuvenation of the mid-face. The choice of products,
depth, and technique of injection depends on the desired level of volume
enhancement and practitioners' preferences.
OBJECTIVE: To describe a
volumizing injection technique in the scope of a controlled, randomized, double
blind, single-center, split-face clinical study. MATERIALS & METHODS: A total of
45 subjects with bilateral symmetrical moderate to severe volume loss in the
malar area received a single 2 mL injection of CPM(r)-26 (Cohesive Polydensified
Matrix(r)) on one side and VYC(r)-20 (VYCROSS(r)) on the contralateral side of
the face. The same injection technique was applied for both sides of the face.
Use of anesthetics, overcorrection, and touch-ups were not permitted. The
investigator completed a product satisfaction questionnaire. Adverse events (AE)
and injection-site reactions (ISRs) were reported during the study.
RESULTS: The products were placed at the epiperiosteal depth in 88.9% (n=40),
at the subdermal depth in 8.9% (n=4) and at both levels in 2.2% (n=1) of
subjects. Fanning technique using cannulae was applied in most cases (97.8%,
n=44). Results of the investigator satisfaction questionnaire allowed to
characterize CPM-26 in comparison to other volumizing gels. Both study products
were generally well tolerated. Local reactions were transient and of mild to
moderate intensity, with the most frequent ones being redness, pain, and
swelling.
CONCLUSION: Adequate injection technique in volumizing
treatments is essential to create a natural aesthetic rejuvenation while
respecting the safety aspect of the procedures. A 22G blunt cannula used with CPM
26 was preferred due to an easier and a more homogeneous distribution of the
product. The investigator also appreciated CPM-26 for its ease of injection,
positioning, lifting, and volumizing capacity.
J Drugs Dermatol.
2017;16(4):351-357.
.
PMID- 28403270
TI - Evidence for Anti-Aging South Korean Cosmeceuticals.
AB - As the market for South Korean skin care products grows in the U.S. and
worldwide, consumers will increasingly seek advice from dermatologists regarding
their efficacy. In this paper, the evidence behind the anti-aging and skin
whitening activity of ingredients in the most popular South Korean skin care
products was reviewed and critically evaluated. Industry profit data from
Euromonitor was obtained to identify the top cosmeceutical brands by retail value
in South Korea. The top selling products and their ingredients were then
identified from individual brand websites. A comprehensive literature search was
conducted using Pubmed to identify and grade the anti-aging and whitening
efficacy for nine popular ingredients: licorice, niacinamide, beta-glucan, snail
mucus, ginkgo biloba, ginseng, green tea, pomegranate, and soy. Of the various
ingredients reviewed, niacinamide, green tea, licorice, and soy have the most
published data for anti-aging and whitening activity. Although the literature
shows modest results, small sample sizes limit interpretation. High-level
evidence to support the use of South Korean skin care products in anti-aging and
skin whitening is lacking.
J Drugs Dermatol. 2017;16(4):358
364.
.
PMID- 28403271
TI - Clinical Assessment of Immediate and Long-Term Effects of a Two-Step Topical
Hyaluronic Acid Lip Treatment.
AB - Key features of lip aging include loss of volume, color, and definition as
well as increases in lines/wrinkles and uneven skin texture. A single-center,
open-label clinical study was conducted to assess the efficacy and tolerability
of a novel, topical two-step lip treatment (HA5 LS) in female subjects presenting
with mild to moderate lip dryness and mild to severe lip condition. Subjects were
instructed to apply HA5 LS at least three times a day to ensure coverage 8 hours
a day for four weeks. Clinical assessments for efficacy and tolerability were
conducted at baseline, baseline post-application, week 2, and week 4.
Standardized digital photography, subject self-assessment questionnaires, and
instrumentation measurements for skin hydration (corneometer) and lip plumpness
(digital caliper) were also conducted. Thirty-six female subjects aged 22-40
years enrolled in the study. HA5 LS provided instant and long term effects,
achieving significant improvements in all clinical grading parameters including
lip texture, color, definition/contour, scaling, cupping, lines/wrinkles, lip
plumpness, and overall lip condition from baseline post-application to week 4
(all P less than equal to .001; Wilcoxon signed-rank test). Instrumentation
measurements for hydration and digital caliper at weeks 2 and 4 were also
significant (all P less than equal to .032; paired t-test). HA5 LS was also well
tolerated and highly-rated by subjects throughout the study duration. Results
from this study suggest that HA5 LS addresses the key features of lip aging,
providing both instant and long-term benefits.
J Drugs Dermatol.
2017;16(4):366-371.
.
PMID- 28403272
TI - Examining HIV Viral Load in a Matched Cohort of HIV Positive Individuals With and
Without Psoriasis.
AB - BACKGROUND: HIV-associated psoriasis is well-documented. Genetic, cellular,
and cytokine profiles have been used as evidence to suggest psoriasis activates
antiviral pathways. There has been a lack of epidemiologic evidence investigating
whether psoriasis patients have lower HIV viral counts compared to non-psoriasis
patients.
OBJECTIVE: Compare the viral load set point of HIV positive
patients with and without psoriasis.
METHODS: A retrospective matched
cohort study of HIV positive patients with and without psoriasis using the Kaiser
Permanente Southern California Health Plan database.
RESULTS: We
identified 101 HIV-positive psoriasis cases; 19 met inclusion criteria and were
matched with 3-5 control patients; 94 total patients were analyzed. The mean age
was 41.4 (12.07) years and 83% were male. Overall, the median log of the viral
load of cases was slightly higher than controls (4.3 vs 4.2; P less than
0.01).
CONCLUSIONS: The serum viral load set point of patients with HIV
and psoriasis was slightly higher than the viral load set point of HIV patients
without psoriasis.
J Drugs Dermatol. 2017;16(4):372-377.
.
PMID- 28403274
TI - The Transposition Flap for the Reconstruction of Lower Cutaneous Lip Defects.
AB - The lower cutaneous lip is a highly visible and functionally sensitive unit,
and numerous factors must be considered when deciding on the optimal repair for
defects in this area. The transposition flap represents an excellent option in
the reconstruction of larger lower cutaneous lip defects. We describe the use of
random pattern transposition flaps for the repair of lower lateral cutaneous lip
defects.
J Drugs Dermatol. 2017;16(4):385-387.
.
PMID- 28403273
TI - The Mechanisms and Potential Impact of Stem Cell Activation in Skin Rejuvenation:
An Evidence-Based Analysis.
AB - Stem cells can propagate indefinitely in an undifferentiated state; or, with
appropriate signals, differentiate into various types of mature cells. Strong
interest in stem cell therapies for degenerative diseases has extended to skin
aging, itself a degenerative process. This article reviews mechanisms of skin
aging, and enables an evidence-based approach to topical skin rejuvenation -
specifically, to formulations labeled as stem cell products.
J Drugs
Dermatol. 2017;16(4):378-384.
.
PMID- 28403275
TI - A Difference in Cutaneous Pigmentary Response to LED Versus Halogen Incandescent
Visible Light: A Case Report from a Single Center, Investigational Clinical Trial
Determining a Minimal Pigmentary Visible Light Dose.
AB - BACKGROUND: While most of the attention regarding skin pigmentation has
focused on the effects on ultraviolet radiation, the cutaneous effects of visible
light (400 to 700nm) are rarely reported. In this report, we describe a case of
painful erythema and induration that resulted from direct irradiation of UV-naive
skin with visible LED light in a patient with Fitzpatrick type II skin.
METHODS AND RESULTS: A 24-year-old healthy woman with Fitzpatrick type II skin
presented to our department to participate in a clinical study. As part of the
study, the subject underwent visible light irradiation with an LED and halogen
incandescent visible light source. After 5 minutes of exposure, the patient
complained of appreciable pain at the LED exposed site. Evaluation demonstrated
erythema and mild induration. There were no subjective or objective findings at
the halogen incandescent irradiated site, which received equivalent fluence (0.55
Watts / cm2). The study was halted as the subject was unable to tolerate the full
duration of visible light irradiation.
CONCLUSION: This case illustrates
the importance of recognizing the effects of visible light on skin. While the
vast majority of investigational research has focused on ultraviolet light, the
effects of visible light have been largely overlooked and must be taken into
consideration, in all Fitzpatrick skin types.
J Drugs Dermatol.
2017;16(4):388-392.
.
PMID- 28403276
TI - [Simultaneity of risk factors for chronic non-communicable diseases in the
elderly in Pelotas, Rio Grande do Sul State, Brazil].
AB - This study aimed to describe the simultaneity of risk factors for chronic non
communicable diseases among the elderly (<= 60 years) in a city in Southern
Brazil. This was a cross-sectional, population-based study of 1,451 elderly in
2013. Cluster analysis was applied to selected risk factors (smoking, alcohol
consumption, excess weight, and physical inactivity). Logistic regression was
used to assess the association between simultaneity of risk factors and socio
demographic variables. The most frequent cluster in men (18.1%) and women (30.7%)
was physical inactivity + excess weight. The cluster alcohol consumption + excess
weight exceeded the expected level in men (O/E = 1.27; 95%CI: 1.01; 1.59) and
women (O/E = 1.72; 95%CI: 1.35; 2.20). The presence of two or more risk factors
in the elderly population (88.1%) points to the need for specific interventions
for this population to fight risk factors simultaneously rather than separately.
PMID- 28403277
TI - User satisfaction with the care of nurses.
AB - Objective: To evaluate user satisfaction with the care of nurses. Methods: Cross
sectional study with a quantitative approach, performed in the medical clinic of
the University Hospital of UFMA/HU/UFMA, with 150 users in the period from
October 2013 to August 2014, through an identification form the and Patient
Satisfaction Instrument. In the data analysis, Student t test, Kruskal Wallis and
Spearman Linear Correlation were used. Results: Users have reported high levels
of satisfaction with all items and domains, with the highest average satisfaction
related to technical and professional domain, followed by the domain trust,
resulting in satisfactory internal consistency in all areas. Gender and level of
education had a positive influence on patient satisfaction. Conclusion: The study
showed that the satisfaction of users admitted to the medical clinic is
correlated with technical skills, scientific knowledge and the individualization
of care provided by nurses.
PMID- 28403278
TI - Patient safety: characterization of YouTube videos.
AB - Objective: To describe how patient safety is addressed in YouTube videos.
Methods: descriptive study with a quantitative approach. Data was collected in
May 2015, at YouTube's search field, with descriptor "patient safety". The sample
included 92 videos, which were analyzed using descriptive statistics. Results:
The videos showed a positive concept of patient safety, based on a systemic
vision that attempts to eliminate the traditional punitive culture by promoting a
culture of safety. Conclusions: The use of videos containing high quality
information may improve the training process of health students and
professionals, as well as raise the individuals' awareness of the importance of
their participation in safety issues.
PMID- 28403279
TI - Acoustic analysis of speech intonation pattern of individuals with Autism
Spectrum Disorders.
AB - Purpose: This study aimed to analyze prosodic elements of speech segments of
students with Autism Spectrum Disorders (ASD) and compare with the control group,
using an acoustic analysis. Methods: Speech recordings were performed with a
sample of individuals with ASD (n = 19) and with typical development (n = 19) of
the male gender, age range: 8-33 years. The prosody questionnaire ALIB (Brazilian
Linguistic Atlas) was used as script, which contains interrogative, affirmative
and imperative sentences. Data were analyzed using the PRAAT software and
forwarded to statistical analysis in order to verify possible significant
differences between the two groups studied in each prosodic parameter evaluated
(fundamental frequency, intensity and duration) and its respective variables.
Results: There were significant differences for the variables tessitura, melodic
amplitude of tonic vowel, melodic amplitude of pretonic vowel, maximum intensity,
minimum intensity, tonic vowel duration, pretonic vowel duration and phrase
duration. Conclusion: Individuals with ASD present significant differences in
prosody compared to those with typical development. It is noteworthy, however,
the necessity of additional studies on the characterization of prosodic aspects
of speech of individuals with ASD with a larger sample and a more restricted age
group.
PMID- 28403280
TI - Electropalatography and its correlation to tongue movement ultrasonography in
speech analysis.
AB - Purpose: To analyze the use of electropalatography and ultrasonography regarding
speech therapy through literature narrative review. Research strategies: A
literature review was conducted at PubMed and Scielo databases, using descriptors
as electropalatography, electropalatography AND evaluation, electropalatography
AND therapy, electropalatography AND ultrasonography, electropalatography AND
speech. Selection criteria: The research criteria selected in the database were:
studies in the past five years and studies in humans. In the pre-selection,
studies that were duplicate, not fully available, and have shown no direct
relation with electropalatography in speech-language therapy were discarded. Data
analysis: Data analysis was performed descriptively, following subdivisions:
title, area, year, subject, implementation, and conclusion of the study. Results:
Twenty one papers were selected, eight of them using the term
electropalatography, two with the keywords electropalatography AND evaluation,
six with the keywords electropalatography AND therapy, three of them with the
keywords electropalatography AND ultrasonography, and two papers with the
keywords electropalatography AND speech. Conclusion: Different types of research
involving the use of electropalatography in the field of speech-language therapy
were found and analyzed. Few researches have concomitantly used
electropalatography and ultrasonography.
PMID- 28403281
TI - Brazilian method for the development terminological subsets of ICNP(r): limits
and potentialities.
AB - Reflection on the limits and potentialities of a Brazilian method for the
development of terminological subsets of ICNP(r),(International Classification
for Nursing Practice) based on the correlation between this method and
international methods. This issue has been debated by the International Council
of Nurses (ICN). Although the council propose a guideline for elaboration, they
encourage and reinforce the use of various perspectives and processes in the
development of subsets. Brazilian Nursing needs to propose a method and deepen
reflections on the use of terminological subsets of ICNP(r) in the reality of the
country. The development of subsets in Brazil is considered incipient and the
proposed method needs to be used and deepened in order to spread the use of
terminology through the application of subsets.
PMID- 28403282
TI - Tuberculosis among prison staff in Rio Grande do Sul.
AB - OBJECTIVE: to evaluate the risk of infection and illness caused by Mycobacterium
tuberculosis among health care and security staff in prisons in two regions of
Rio Grande do Sul (RS). METHOD: cross-sectional study involving prison staff. An
interview and sputum smear microscopy and culture were performed. Latent
infection was evaluated according to the result of the tuberculin test (TT), self
referred. RESULTS: among staff who had a TT, 10 (83.3%) in the central region and
2 (16.7%) in the southern region were considered reactors. Length of employment
among prison officers who reacted to TT was 15.3 years, and among health care
workers, 4.1 years (p = 0.01). No cases of active tuberculosis (TB) were
identified. CONCLUSION: prevalence of latent TB was 27.9%. Length of employment
between different professional categories and their working regions was
considered a risk factor for latent TB.
PMID- 28403283
TI - Nursing care in early childhood: contributions from intersubjective recognition.
AB - OBJECTIVE: to understand the elements composing intersubjective recognition that
are relevant for nursing care in early childhood in favor of comprehensive child
development. METHOD: reflexive study based on the Honnethian concept of
intersubjective recognition in the dimensions of affection, defense of rights,
and social esteem. RESULTS: nursing knowledge and practices, permeated by the
intersubjective recognition in the mentioned dimensions, contribute to the
dynamism of interpersonal relations, the production of co-responsibility, and
shared construction of health care in early childhood, with benefits to
comprehensive development. CONCLUSION: a successful coordination of the three
intersubjective dimensions enables the expansion of the understanding on
childhood and nursing care in child health in the field of human development
promotion, covering affection, defense of rights, and social esteem in the
established relationships with future positive individual and social
possibilities.
PMID- 28403284
TI - Unna's boot: experience of care of people with venous ulcers.
AB - OBJECTIVE: to understand the experience of care of people with venous ulcers
using an Unna's boot. METHOD: a qualitative study, based on the social
phenomenology by Alfred Schutz, was carried out with 12 adults interviewed in
2015. The statements were analyzed and organized in thematic categories. RESULTS:
the following categories emerged: "Unna's boot annoyance versus wound
improvement", "Difficulties for accessing care with the Unna's boot", "Care for
healing and preventing recurrence", and "Receiving more attention from the
healthcare professional". CONCLUSION: the experience of care of people using an
Unna's boot revealed the annoyance caused by this device, which was overcome due
to the wound improvement. However, access to care was compromised by the lack of
structure at the service, frustrating the patients' expectations regarding wound
healing. The issues of these people's intersubjective universe should be
considered in the management of care of venous ulcers.
PMID- 28403285
TI - Spanish version of the scale of attitudes toward alcohol, alcoholism and
alcoholics: content validation.
AB - : ABSTACT Objective: to describe the process of translation and cultural
adaptation of the scale of attitudes towards alcohol, alcoholism and alcoholics
into the Spanish language. METHODS: this was a methodological study, which
followed the international guidelines for translation and adaptation of
measurement scales. RESULTS: During the process of translation and cultural
adaptation of scale of attitudes towards alcohol, alcoholism and alcoholics to
the Spanish language, the items were adjusted based on semantic, idiomatic and
conceptual equivalence of the expressions contained in the scale of attitudes
towards alcohol, alcoholism and alcoholics. Content validation indicated
satisfactory validity indexes, with Intraclass Correlation Coefficient (ICC)
(0.97), Content Validity Index (CVI) (0.92), and the Prevalence Adjusted Bias
Adjusted Kappa (PABAK) (0.80). CONCLUSION: the scale of attitudes towards
alcohol, alcoholism and alcoholics, adapted and translated into the Spanish
language, presented content validity with satisfactory indexes, which affirmed
that the instrument was adapted for the Colombian context. The next step will be
evaluation of its psychometric properties in order to guarantee reliability for
its use in Hispanic populations.
PMID- 28403286
TI - Nursing care protocol for patients with a ventricular assist device.
AB - OBJECTIVE: to develop and validate a nursing care protocol for patients with a
ventricular assist device (VAD). METHOD: descriptive study, with a quantitative
approach, for an instrument's methodological validation. Three stages were
conducted: development of the instrument; protocol content validation according
to the Delphi technique, and agreement among experts and the scientific
literature. RESULTS: based on the content validation, a care protocol for
patients with a VAD was created and assessed by Spanish experts. Of the 15 items
evaluated by means of the content validity index (CVI), 10 presented solid
evidence of validation, with Kappa ranging between 0.87 and 1. CONCLUSION: the
method enabled the validation of interventions that will contribute to qualified
and standardized care for patients with a VAD.
PMID- 28403287
TI - Nasoenteral tube: factors associated with delay between indication and use in
emergency services.
AB - OBJECTIVE: to know the time between indication and use of a nasoenteral tube
(NET) and factors associated with delays. METHOD: A prospective cohort study that
followed adults in a Brazilian emergency department, since the indication of the
use of a NET, evaluating clinical variables and the work process. The Generalized
Estimated Equations model was adopted to identify factors associated with the
delays in each stage of the process. RESULTS: the time between indication and use
of NET was 573 (IQR: 3601,093) minutes, in 150 insertions of NET. Insertions in
patients who previously did not use it; delays in the medical, nutrition, and
nursing care routine; use of mechanical ventilation; noradrenaline; and fasting
were factors for longer time before the use of the tube. CONCLUSION: the time
between indication and use of NET was high, exceeding 10 hours in half of the
cases. Factors related to the clinical condition of the patient and to the care
management would contribute to delays.
PMID- 28403288
TI - Prevalence of Metabolic Syndrome in individuals with Type 2 Diabetes Mellitus.
AB - OBJECTIVE: to identify the prevalence of Metabolic Syndrome and its components in
a population of patients with type 2 Diabetes Mellitus. METHOD: a cross-sectional
study was conducted with 201 diabetic patients. A descriptive analysis and Chi
square and Fisher's exact tests ( p <0.05) were performed. RESULTS: the majority
of participants were females and overweight, with a mean age of 63.1 years and a
low level of education, and categorized as physically inactive. Of all
individuals investigated, 50.7% were diagnosed with Metabolic Syndrome and 92%
had at least one of the syndrome components with values beyond those recommended.
CONCLUSION: it is essential to take preventive actions and develop studies that
help to identify the factors associated with this syndrome.
PMID- 28403289
TI - Hand hygiene as a caring practice: a reflection on professional responsibility.
AB - Hand hygiene represents a fundamental nursing care practice and is traditionally
considered the most important and effective measure in the prevention and control
of healthcare-related infections. However, studies indicate that adherence to the
procedure is unsatisfactory throughout the world, and show low adherence rates.
In a context in which patient safety stands out as a priority, this text submits
refl ections about professional responsibility when not adhering to hand hygiene
practices, and ethical aspects related to this conduct.
PMID- 28403290
TI - Non-pharmacological measures in preterm newborns submitted to arterial puncture.
AB - OBJECTIVE: to assess pain in preterm newborns and to compare the neonatal and
therapeutic variables with the total scores of the Neonatal Facial Coding System
of preterm newborns submitted to arterial puncture exposed to music and 25% oral
glucose. METHOD: a comparative study with 48 recordings of preterm newborns -
Group 1, music (26); Group 2, glucose 25% (22) - individually analyzed by three
trained nurses, after Kappa of at least 80%. RESULTS: the variables and the pain
scores of the groups did not present statistical significance (p < 0.05)
according to the Neonatal Facial Coding System. 80.8% of the preterm infants in
Group 1 had a higher quantitative score >= 3 in the neonatal variables (gender,
type of delivery), and therapeutic variables (type of oxygen therapy, place of
hospitalization, type of puncture). CONCLUSION: There was no difference when
comparing the music and glucose 25% groups and the variables studied.
PMID- 28403291
TI - Impact of home visits on the functional capacity of patients with venous ulcers.
AB - OBJECTIVE: to compare the impact of home visits, before and after instructions,
on the functional capacity of adult and elderly patients with venous ulcers, by
means of the KATZ-EIAVD Scale. METHOD: experimental, clinical, randomized, non
blind and controlled study, developed with 32 patients (case and control groups).
The research settings were the Wound Care Clinic of the University Hospital
Antonio Pedro, and the homes of patients assisted in this clinic. Data collection
took place from February to June 2014, by means of a health unit evaluation tool,
the KATZ-EIAVD Scale, and a script of instructions to be given to the research
subjects that had received a home visit. RESULTS: the studied population present
excellent independence for activities of daily living, with no significant
variation among them. CONCLUSION: the studied groups have functional capacity
with similar progress.
PMID- 28403292
TI - Semiotics and semiology of Nursing: evaluation of undergraduate students'
knowledge on procedures.
AB - OBJECTIVE: to assess the knowledge of scholars on Nursing regarding simple hands
hygiene (SHH), blood pressure measurement (BP), peripheral venipuncture (PV) with
venous catheter and male urethral catheterization delay (UCD) procedures. METHOD:
quantitative study carried out between February and May 2014, with 186
undergraduate Nursing students from 5th to 9th period of a public university of
Rio Grande do Norte, with application of four questionnaires. One carried out
descriptive and analytic analysis. RESULTS: the students presented low average
percentage of right answers, especially in blood pressure measurement (55.5%);
SHH's average was higher than 70%. The average of correct answers was the highest
in SHH (8.6), followed by UCD (7.8), PV (7.4) and BP (6.7). The questions
regarding the topic "concepts" showed less correct answers when comparing it to
the topic "technique steps". CONCLUSION: it is necessary to establish knowledge
monitoring strategies, in order to stimulate the constant improvement.
PMID- 28403293
TI - Viral hepatitis: a challenge for nursig.
PMID- 28403294
TI - The family in face of the elderly's reality of living alone.
AB - OBJECTIVE: to understand the family dynamics in face of the reality of the
elderly living alone. METHOD: study of qualitative approach with theoretical
reference of symbolic interactionism that involved interviews with families. Data
were analyzed by thematic analysis. RESULTS: six families participated in the
study. The discourse analysis originated the following categories: The family
respecting their decision making; The family organizing itself to the process of
living alone after the age of 80 years; The family experiencing the freedom of
living alone. CONCLUSION: in this study, it was possible to identify the
facilitation of the possibility of living alone with preparation and agreements
between the family during the family life cycle, leading to the feeling of
freedom and quality of life of all members. Nursing, as a science responsible for
elaborating care strategies, should work together with families to assist in the
planning of care plans based on the individual social reality of the family.
PMID- 28403295
TI - Systematization of nursing care and the formation of professional identity.
AB - The aim of this study is to explore arguments that broaden the understanding of
possible links between the organization of nursing care and the structuring of
professional identity. For that purpose, some aspects related to these themes are
addressed, highlighting issues regarding differences in the concepts of the
organization of nursing care and the nursing process, as well as the performance
of this activity and its possible impact on the establishment of its relationship
with the professional identity. Emphasis is given to the need to stimulate the
debate on the subject by nursing professionals involved in the training of human
resources and the provision of care, as well as in class entities, in order to
deepen understanding of these concepts as significant elements for strengthening
our professional identity.
PMID- 28403296
TI - Moral suffering among nurse educators of technical courses in nursing.
AB - OBJECTIVE: to understand situations of moral suffering experienced at work by
nurse educators of technical courses in nursing. METHOD: a qualitative study with
discursive textual analysis by means of semi-structured interviews with ten nurse
educators at two professional educational institutions in southern Brazil.
RESULTS: two categories were established: lack of commitment on the part of
students to the future profession, expressed through disrespect and disregard for
the work of nurse educators, with inappropriate behaviors and attitudes; and lack
of commitment to the learning-teaching process, expressed by indifference to the
professional profile and lack of interest in lessons and care practices
associated with learning gaps. CONCLUSION: these situations have an impact on
experiences of moral suffering by nurse educators, and show a need for rethinking
their practice, relationships, and educational spaces, and implementing
strategies to favor the confrontation of dilemmas and conflicts experienced in
educational practice in technical courses in nursing.
PMID- 28403297
TI - Knowledge of the nursing team on pressure ulcer prevention.
AB - OBJECTIVE: describe and analyze the nursing team's knowledge about
classification, evaluation and measures to prevent pressure ulcers (PU) in
patients hospitalized in the ICU of a teaching hospital in the city of Manaus.
METHOD: a descriptive and exploratory study was conducted after approval by a
research ethics committee. Data were collected using a validated instrument. The
study sample was made up of 40 nursing staff members, of whom 14 were nurses and
26 were nursing technicians/aides. Data were analyzed through descriptive
statistics and Student's t-test, with value of p<0.05. RESULTS: the overall mean
of hits was 63.4% for technicians/aides and 51.4% for nurses, with statistically
significant differences between the groups only for the PU prevention category
(p<0.001). CONCLUSION: a deficit of knowledge on PU prevention was found among
nurses and nursing technicians/aides, demanding the training of these
professionals.
PMID- 28403298
TI - Portable bathtub: technology for bed bath in bedridden patients.
AB - OBJECTIVE: determine the benefits of the Portable Bathtub as technology for bed
bath in bedridden patients. METHOD: qualitative research of exploratory
descriptive character, whose data were collected by means of 30 interviews with
patients, family members and professionals directly involved in bed bath, carried
out with Portable Bathtub, in bedridden patients of a medical clinic, from July
to December 2015. RESULTS: from the data encoded by thematic content analysis
resulted two categories: Portable Bathtub: from morphine to the patient's
rekindled eyes; From mechanized practice to unique, transforming care.
CONCLUSION: we concluded that the Portable Bathtub constitutes enhancing
technology, as it enables clinical improvement of the patient's general condition
and transcends traditional mechanized practices by the reach of advanced nursing
care practices.
PMID- 28403299
TI - Religious and spiritual coping in people living with HIV/Aids.
AB - OBJECTIVE: evaluate the religiosity and the religious/spiritual coping of people
living with HIV/Aids. METHOD: descriptive, cross-sectional study with
quantitative approach, conducted in a reference HIV/Aids outpatient clinic in a
university hospital of Recife-PE, Brazil, from June to November 2015. At total of
52 people living with HIV/Aids (PLWHA) participated in the research, which
employed own questionnaire, the Duke University Religion Index (DUREL), and the
Religious/Spiritual Coping Scale (RCOPE). RESULTS: the sample presented high
indices of organizational religiosity (4.23+/-1.66), non-organizational
religiosity (4.63+/-1.50), and intrinsic religiosity (13.13+/-2.84). Positive
RCOPE was used in high mean scores (3.66+/-0.88), and negative RCOPE had low use
(2.12 +/- 0.74). In total, use of RCOPE was high (3.77+/-0.74), having
predominated the positive RCOPE (NegRCOPE/PosRCOPE ratio=0.65+/-0.46).
CONCLUSION: it is evident the importance of encouraging religious activity and
RCOPE strategies, seen in the past as inappropriate interventions in clinical
practice.
PMID- 28403300
TI - Multi-professional team's perception of nurses' competences in liver
transplantations.
AB - : Objective describe the multi-professional team's perception of nurses'
competences in liver transplantation programs. METHOD: descriptive study with a
qualitative approach. Data were collected through a questionnaire. Participants
were 12 professionals of the liver transplantation team of a reference hospital.
For result interpretation, the thematic analysis technique was employed. RESULTS:
the professionals assessed the competences employed by nurses as proactive,
autonomous, creative, humanized, capable of teamwork, decision-making and
conflict management. CONCLUSION: this study made it possible to demonstrate that
members of the multi-professional team perceived nurses as professionals capable
of coordinating and integrating the skills "knowing, doing, being and co
existing", enabling quality care for candidates and receivers of liver
transplants, as well as for their families and/or caregivers in all perioperative
phases.
PMID- 28403301
TI - Conformity of nurse prescribing to care needs: nurses' understanding.
AB - OBJECTIVE: investigate the understanding of nurses on nurse prescribing
conformity to the care needs of hospitalized patients and factors associated with
that conformity. METHOD: a descriptive study, with a quantitative approach, was
conducted at 20 in-patient units of a teaching hospital in the state of Sao
Paulo. The participants (N=139) answered a semi-structured questionnaire.
RESULTS: For 43 (30.9%) nurses, nurse prescribing is always in line with
patients' care needs. The fields of body care and elimination, skin and mucosa
care and investigation and monitoring were the most frequently addressed.
CONCLUSION: in the perception of most nurses, nurse prescribing does not conform
with patients' health heeds. The establishment of strategies to improve
prescribing quality is recommended, as well as the development of permanent
qualification programs and the systematic use of instruments for assessment of
patients' care demands regarding nursing.
PMID- 28403302
TI - Moral sensitivity in Primary Health Care nurses.
AB - OBJECTIVE: to characterize the profile and describe the moral sensitivity of
primary health care nurses. METHOD: this is a quantitative, transversal,
exploratory, descriptive study. The data were collected through the Moral
Sensitivity Questionnaire translated and adapted to Brazil. 100 primary health
care nurses participated, from Rio Grande do Sul, Brazil. The data collection
took place during the months of March and July 2016, in an online form. The
analysis of the data occurred through descriptive statistical analysis. RESULTS:
the nurses had an average moral sensitivity of 4.5 (out of 7). The dimensions
with the greatest moral sensitivity were: interpersonal orientation, professional
knowledge, moral conflict and moral meaning. CONCLUSION: the nurses of Rio Grande
do Sul have a moderate moral sensitivity, which may contribute to a lower quality
in Primary Health Care.
PMID- 28403303
TI - The game as strategy for approach to sexuality with adolescents: theoretical
methodological reflections.
AB - OBJECTIVE: To describe the Papo Reto [Straight Talk] game and reflect on its
theoretical-methodological basis. METHOD: Analytical study on the process of
elaboration of the Papo Reto online game, destined to adolescents aged 15-18
years, with access to the Game between 2014 and 2015. RESULTS: the interactions
of 60 adolescents from Belo Horizonte and Sao Paulo constituted examples of the
potentialities of the Game to favor the approach to sexuality with adolescents
through simulation of reality, invention and interaction. Based on those
potentialities, four thinking categories were discussed: the game as pedagogic
device; the game as simulation of realities; the game as device for inventive
learning; and the game empowering the interaction. CONCLUSION: By permitting that
the adolescents take risks on new ways, the Game allows them to become creative
and active in the production of senses, in the creation of their discourses and
in the ways of thinking, feeling and acting in the sexuality field.
PMID- 28403304
TI - Dimensioning the instrumentation: Exploratory or confirmatory factor analysis?
PMID- 28403305
TI - Satisfaction and dissatisfaction in the work of recyclable solid waste
segregators: convergent-care research.
AB - OBJECTIVES: describe elements that promote satisfaction and dissatisfaction in
the work of recyclable solid waste segregators and conduct a nursing action
focused on these elements. METHOD: qualitative research, convergent-care,
conducted with members of the cooperative. Data production occurred during 2015
through participation observation, semi-structured interviews, and a convergence
group. Analysis comprised the phases Apprehension, Synthesis, Theorization, and
Transference. RESULTS: four categories emerged. They showed satisfaction and
dissatisfaction related to identification with tasks and work content, material
and personal gains obtained from solid waste segregation, prejudice, lack of
appreciation, and difficulties in interpersonal relationships. This last item,
due to its importance, received a nursing action. CONCLUSION: the study
contributed to the advancement of knowledge and the association of possibilities
between the research performance and nursing care for workers.
PMID- 28403306
TI - Quality of life of patients who undergone myocardial revascularization surgery.
AB - OBJECTIVE: to evaluate the quality of life of patients who underwent
revascularization surgery. METHOD: a descriptive, cross sectional study, with
quantitative approach carried out with 75 patients. The questionnaire WHOQOL-Bref
was used to evaluate the quality of life (QOL). RESULTS: patients' QOL evaluation
presented a moderate result, with need of improvement of all domains. Low income
patients had the worst evaluation of QOL in the domain environment (p=0,021), and
the ones from Recife/metropolitan area, in the domain social relationship
(p=0,021). Smoker (p=0,047), diabetic (p=0,002) and alcohol consumption (p=0,035)
patients presented the worst evaluation of the physical domain. Renal patients
presented the worst evaluation of QOL in the physical (P=0,037), psychological
(p=0,008), social relationship (p=0,006) domains and total score (p=0,009).
CONCLUSION: the improvement of QOL depends on the individual's process of
behavioral change and the participation of health professionals is essential to
formulate strategies to approach these patients, especially concerning health
education.
PMID- 28403307
TI - Direct cost of monitoring conventional hemodialysis conducted by nursing
professionals.
AB - OBJECTIVE: to analyze the mean direct cost of conventional hemodialysis monitored
by nursing professionals in three public teaching and research hospitals in the
state of Sao Paulo, Brazil. METHOD: this was a quantitative, explorative and
descriptive investigation, based on a multiple case study approach. The mean
direct cost was calculated by multiplying (clocked) time spent per procedure by
the unit cost of direct labor. Values were calculated in Brazilian real (BRL).
RESULTS: Hospital C presented the highest mean direct cost (BRL 184.52), 5.23
times greater than the value for Hospital A (BRL 35.29) and 3.91 times greater
than Hospital B (BRL 47.22). CONCLUSION: the costing method used in this study
can be reproduced at other dialysis centers to inform strategies aimed at
efficient allocation of necessary human resources to successfully monitor
conventional hemodialysis.
PMID- 28403308
TI - Patient with stroke: hospital discharge planning, functionality and quality of
life.
AB - : Stroke still causes high levels of human inability and suffering, and it is one
of the main causes of death in developed countries, including Portugal.
OBJECTIVE: analyze the strategies of hospital discharge planning for these
patients, increasing the knowledge related to hospitalhome transition, discharge
planning processes and the main impact on the quality of life and functionality.
METHOD: integrative literature review using the PICOD criteria, with database
research. RESULTS: 19 articles were obtained, using several approaches and
contexts. For quality of life, the factors related to the patient satisfaction
with care and the psychoemotional aspects linked with functionality are the most
significant. CONCLUSION: during the hospitalization period, a careful hospital
discharge planning and comprehensive care to patients and caregivers - in
particular the functional and psychoemotional aspects - tend to have an impact on
the quality of life of patients.
PMID- 28403309
TI - Self-esteem and health-related quality of life in ostomized patients.
AB - OBJECTIVE: to assess self-esteem (SE) and health-related quality of life (HRQoL)
in ostomized patients due to colorectal cancer. METHOD: cross sectional research
with a quantitative approach. Three instruments were used for data collection:
one instrument containing sociodemographic and clinical data, Rosenberg's Self
Esteem Scale, and the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire. RESULTS: SE and HRQoL were considered
satisfactory. Significant statistical difference was found in the social function
domain and marital status, ostomy duration, location, and time; global health
scale and ostomy type; cognitive function and pain in the ostomy site. There was
a correlation between self-esteem and all the functional scales and the global
health scale. CONCLUSION: knowing SE and HRQoL levels, in addition to the
variables that influence them, supports ostomized patients' care planning,
rehabilitation, and social autonomy.
PMID- 28403310
TI - The elderly recognizing themselves as vulnerable to falls in the concreteness of
the femoral fracture.
AB - OBJECTIVES: understand the experience of the elderly with falls followed by
femoral fracture and elaborate theoretical model of this process of lived
experience. METHOD: qualitative research with theoretical saturation through
analysis of the ninth nondirected interview of elderly who underwent such
experience. Interviews were recorded, transcribed, and analyzed according to
Grounded Theory. RESULTS: three categories emerged (sub-processes): evaluating
signs and symptoms of fracture after the fall; feeling sad and insecure with the
new condition; and finding oneself susceptible to fractures. From realignment of
these categories (sub-processes) we could abstract the central category
(process), recognizing oneself as vulnerable to falls in the concreteness of the
fracture. CONCLUSION: the theoretical model considering the Symbolic
Interactionism signals the implementation of continued program for fall
prevention, with teaching strategies that encourage the elderly to reflect on the
concreteness of contexts in which there is risk of occurring injury to their
health.
PMID- 28403311
TI - Focus group on qualitative research: experience report.
AB - OBJECTIVE: to report the experience of applying the focus group technique for
production of data in qualitative research. METHOD: four group sessions were held
from May to June 2015, with the participation of professionals from the public
sector of PHC and from specialized service. RESULTS: the way focus group was
developed is described in steps: planning, recruitment, ambience, group sessions,
and evaluation. CONCLUSION: we highlight that the focus group, as a technique to
produce data in collective space, can contribute not only to the construction of
knowledge in Nursing, but also to the research approach with the assistance
practice.
PMID- 28403312
TI - Nursing throughout war times: political propaganda and professional valorization
(1942-1945).
AB - OBJECTIVE: to discuss the symbolic effects of the publication on written press of
institutional rites related to the courses promoted by the Brazilian Federal
District's Schools of Nursing during the Second World War. METHOD: exploratory
and documentary study, whose sources were treated by historical method. RESULTS:
one noticed, in the news reports analyzed, that the Brazilian Estado Novo has
used nurses images to divulge within the society the woman's acting altruistic
model in service to the country, through the systematic diffusion by the press of
her honorable acting during the war, what assured the amplification of the
visibility and acknowledgment of the Nursing profession in that context.
CONCLUSION: the diffusion by press of emergency nurses graduations magnified
their apparition in public spaces, occasion on which the institutional rite was
strategically used to transmit to the society the urgency of the new profession,
in order to support the political causes in vigor in the country.
PMID- 28403313
TI - Educational action research on Facebook(r): combining leisure and learning.
AB - Objective: To analyse the path of dialogical education in leisure and mental
health in social media. Method: Action research based on the theoretical
methodological framework of Paulo Freire, conducted with 11 nursing students of a
public university in the state of Parana, Brazil, during seven days of June 2015,
in a closed group on Facebook(r). The dialogues were called, 'Virtual Culture
Circles' and preceded by self-administered questionnaires that addressed the
relationship between leisure and mental health. The data were analysed in an
interpretive way, using the encoding and decoding proposed by Freire. Results:
The students related leisure to pleasurable activities and quality of life;
however, it is not widely or critically practiced in their personal lives or
education. Conclusions: The Virtual Culture Circles provided emancipatory
dialogues and a critical analysis of the subject matter, with possible
repercussions on the personal and professional lives of the subjects.
PMID- 28403314
TI - Implementation of care practices to prevent and repair perineal trauma in
childbirth.
AB - Objective: To implement care practices for perineal trauma prevention and
repairing in normal birth. Method: Quasi-experimental study conducted at Hospital
da Mulher Mae-Luzia, in Macapa, AP, Brazil. Seventy-four (74) nurses and
obstetricians and 70 post-partum women were interviewed and the records of 555
patients were analyzed. The study was conducted in three stages: pre-audit and
baseline audit (phase 1); educational intervention and implementation of best
practices (phase 2); post-implementation audit (phase 3). Data was analyzed by
comparison of the results of phases 1 and 3. Results: Following the educational
intervention, a lower number of health professionals encouraged directed pushing,
performed episiotomies and repaired first-degree lacerations; more women reported
lithotomy position; more patient records indicated the use of VicrylTM to suture
the perineal mucosa and skin. Conclusion: The educational intervention improved
birth care and perineal outcomes. Nevertheless, gaps were identified in the
implementation of evidence, as well as inappropriate perineal care management.
PMID- 28403315
TI - Home intervention as a tool for nursing care: evaluation of the satisfaction of
the elderly.
AB - Objective: To evaluate the results of home nursing interventions according to the
satisfaction of the elderly users. Methods: Ex-post facto evaluative, qualitative
and descriptive research, conducted from November 2015 to January 2016 with 12
dependent elderly individuals accompanied by an extension project in the city of
Maringa, PR, Brazil. Data were collected after home interventions based on the
Single-User Treatment Project, by means of semi-structured interviews subjected
to content analysis and the theoretical framework of Donabedian. Results: The
following thematic categories emerged: "home nursing intervention: synonymous
with joy, distraction and bonding" and" home nursing intervention: health and
lifestyle transformations". Conclusion: The home nursing interventions had
positive results that signal the quality of the provided care.
PMID- 28403316
TI - Educational video as a healthcare education resource for people with colostomy
and their families.
AB - Objective: To know the perceptions of participants in a support group for people
with colostomy on the use of video as a resource for health education. Method:
Qualitative research with 16 participants in a support group for people with
colostomy in Santa Maria, Rio Grande do Sul, Brazil. Data were collected in April
and May of 2016, through a focus group, and subjected to the thematic analysis
proposed by Minayo. Results: The results led to three categories: care and self
care are learned alone: the lived reality; health education and learning through
educational video: perceived opportunities; the singularities of the educational
video from the viewpoint of people with colostomy and their families. Conclusion:
The scarcity of guidelines retards independence and hinders autonomy in care and
self-care. The audio-visual technology applied in this study complements the
educational guidelines, and can enable changes and the opportunity to rethink
pedagogical nursing practices.
PMID- 28403317
TI - Attention, memory, visuoconstructive, and executive task performance in
adolescents with anxiety disorders: a case-control community study.
AB - Objective:: The aim of the present study was to assess children and adolescents
with mild and severe anxiety disorders for their performance in attention, verbal
episodic memory, working memory, visuoconstructive skills, executive functions,
and cognitive global functioning and conduct comparative analyses with the
performance of children free from anxiety disorders. Methods:: Our sample
comprised 68 children and adolescents aged 10 to 17 years (41 with current
diagnoses of anxiety disorders and 27 controls) selected from a larger cross
sectional community sample of adolescents. Children and adolescents with anxiety
disorders were categorized into two groups on the basis of anxiety severity (mild
or severe). All participants underwent a neuropsychological assessment battery to
evaluate attention, verbal episodic memory, working memory, visuoconstructive
skills, and executive and cognitive functions. Results:: No differences were
found in any neuropsychological tests, with the single exception that the group
with mild anxiety had better performance on the Digit Span backward test compared
to subjects with severe anxiety and to controls (p = 0.041; eta2 = 0.11).
Conclusions:: Not only might anxiety disorders spare main cognitive functions
during adolescence, they may even enhance certain working memory processes.
PMID- 28403318
TI - Screening for symptoms of anxiety and depression in patients admitted to a
university hospital with acute coronary syndrome.
AB - Objective:: To investigate the prevalence of anxiety and depression in patients
admitted for acute coronary syndrome to a university hospital and to examine
associations with use of psychotropic drugs. Methods:: Ninety-one patients who
had had an acute coronary event were enrolled on this cross-sectional prevalence
study. Characteristics of the study population and the prevalence rates of
depression and anxiety in the sample were assessed using the Hospital Sao Lucas
da Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) psychiatric
consultation protocol, which includes clinical and sociodemographic data, and the
Hospital Anxiety and Depression Scale (HADS). Results:: The prevalence of
symptoms of anxiety was 48.4% (44 patients) and the prevalence of depressive
symptoms was 26.4% (24 patients). Of these, 19 patients (20.9% of the whole
sample) had scores indicative of both types of symptoms concomitantly.
Considering the whole sample, just 17 patients (18.7%) were receiving treatment
for anxiety or depression with benzodiazepines and/or antidepressants.
Conclusions:: Anxiety and depression are disorders that are more prevalent among
patients with acute coronary syndrome than in the general population, but they
are generally under-diagnosed and under-treated. Patients with anxiety and
depression simultaneously had higher scores on the HADS for anxiety and
depression and therefore require more intensive care.
PMID- 28403319
TI - Assessment of factors related to smokers' adherence to a short-term support group
for smoking cessation: a longitudinal study in a developing country.
AB - Objective:: The aim of this study was to determine which individual
characteristics of smokers are associated with their adherence to a support group
for smoking cessation. Methods:: Smokers from Porto Alegre, Brazil, were invited
to participate in a support group for smoking cessation consisting of four weekly
sessions. Demographic data, smoking history, presence of tobacco-related
diseases, severity of nicotine dependence, stage of motivation, and symptoms of
anxiety and depression were evaluated at baseline. Adherence was defined as
attendance at group sessions and was measured at the second and fourth sessions
of the program. Results:: The study recruited 167 smokers who attended the first
meeting and met criteria for admission to the study. One hundred and two of the
participants returned to the second session and only 55 of those who attended the
first meeting completed the four-week program. For immediate adherence (second
session), adult smokers over the age of 35 were more likely to adhere to the
treatment (p = 0.004), whereas smoking higher numbers of cigarettes per day was
associated with lower adherence to attendance at group meetings (p = 0.031). For
final adherence (fourth session), only minimal level symptoms of anxiety were
associated with a higher likelihood of adherence (p = 0.02). Conclusions:: Older
smokers, those who smoked fewer cigarettes per day, and those with lower levels
of anxiety exhibited higher rates of adherence to a smoking cessation support
group.
PMID- 28403320
TI - A proposal for a new Brazilian six-item version of the Edinburgh Postnatal
Depression Scale.
AB - Introduction:: Factor analysis of the Edinburgh Postnatal Depression Scale (EPDS)
could result in a shorter and easier to handle screening tool. Therefore, the aim
of this study was to check and compare the metrics of two different 6-item EPDS
subscales. Methods:: We administered the EPDS to a total of 3,891 women who had
given birth between 1 and 3 months previously. We conducted confirmatory and
exploratory factor analyses and plotted receiver-operating characteristics (ROC)
curves to, respectively, determine construct validity, scale items' fit to the
data, and ideal cutoff scores for the short versions. Results:: A previously
defined 6-item scale did not exhibit construct validity for our sample.
Nevertheless, we used exploratory factor analysis to derive a new 6-item scale
with very good construct validity. The area under the ROC curve of the new 6-item
scale was 0.986 and the ideal cutoff score was >= 6. Conclusions:: The new 6-item
scale has adequate psychometric properties and similar ROC curve values to the10
item version and offers a means of reducing the cost and time taken to administer
the instrument.
PMID- 28403321
TI - Depression, anxiety, hopelessness and quality of life in users of cocaine/crack
in outpatient treatment.
AB - Objective:: To identify symptoms of anxiety, depression, and feelings of
hopelessness in patients in outpatient treatment for substance dependency and to
test for correlations with various aspects of their quality of life. Methods:: A
cross-sectional study of a sample of 25 men in recuperation from substance
dependency, selected by convenience. We assessed symptoms of depression (Beck
Depression Inventory-II), anxiety (Beck Anxiety Inventory), hopelessness (Beck
Hopelessness Scale), and quality of life (World Health Organization Quality of
Life instrument-Abbreviated version [WHOQOL-Bref]), and also analyzed
sociodemographic profile, substance abuse, and family history. Categorical
variables were expressed as frequencies and percentages and quantitative
variables as means and standard deviations or as medians and interquartile
ranges. We also analyzed Spearman correlations to a 5% significance level.
Results:: The study revealed prevalence rates of 32% for depression, 24% for
anxiety, and 12% for hopelessness, at a moderate/severe level. Correlations
between Beck scales and WHOQOL-Bref were significant; but impacts differed in the
four areas evaluated. Conclusions:: Overall, we observe global negative impacts
on subjects' lives, affecting their psychiatric symptoms and quality of life and
their relationships and occupational factors to a similar degree. The results
show that the lower the scores on these scales, the better the quality of life in
some areas, indicating that there is a negative correlation between psychiatric
symptoms and quality of life.
PMID- 28403323
TI - A critical review of trials of transcranial direct current stimulation and
trigeminal nerve stimulation for depression: the issue of treatment-emergent
mania.
AB - Objective:: This study is a critical review analyzing occurrence of treatment
emergent mania (TEM) related to transcranial direct current stimulation (tDCS)
and trigeminal nerve stimulation (TNS). Method:: We present a systematic review
of the literature on TEM related to tDCS and TNS treatment for major depressive
disorder (MDD), conducted in accordance with the recommendations from Cochrane
Group and the PRISMA guidelines. Results:: Our search identified few reported
episodes of TEM in the literature. In fact, we found 11 trials focused on
treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three
open label and one controlled). We highlight the need for safety assessment in
clinical research settings to establish with precision and in larger samples the
risks inherent to the technique under investigation. Conclusion:: Safety
assessment is of fundamental importance in clinical research. TEM is a very
important safety issue in MDD trials. Further and larger controlled trials will
help to clarify both the safety and the clinical effects of combinations of
pharmacotherapy and tDCS or TNS in daily clinical practice.
PMID- 28403322
TI - Serum concentrations of brain-derived neurotrophic factor in patients diagnosed
with gender dysphoria undergoing sex reassignment surgery.
AB - Introduction:: Transsexualism (ICD-10) is a condition characterized by a strong
and persistent dissociation with one's assigned gender. Sex reassignment surgery
(SRS) and hormone therapy provide a means of allowing transsexual individuals to
feel more congruent with their gender and have played a major role in treatment
over the past 70 years. Brain-derived neurotrophic factor (BDNF) appears to play
a key role in recovery from acute surgical trauma and environmentally mediated
vulnerability to psychopathology. We hypothesize that BDNF may be a biomarker of
alleviation of gender incongruence suffering. Objectives:: To measure
preoperative and postoperative serum BDNF levels in transsexual individuals as a
biomarker of alleviation of stress related to gender incongruence after SRS.
Methods:: Thirty-two male-to-female transsexual people who underwent both surgery
and hormonal treatment were selected from our initial sample. BDNF serum levels
were assessed before and after SRS with sandwich enzyme linked immunosorbent
assay (ELISA). The time elapsed between the pre-SRS and post-SRS blood
collections was also measured. Results:: No significant difference was found in
pre-SRS or post-SRS BDNF levels or with relation to the time elapsed after SRS
when BDNF levels were measured. Conclusion:: Alleviation of the suffering related
to gender incongruence after SRS cannot be assessed by BDNF alone. Surgical
solutions may not provide a quick fix for psychological distress associated with
transsexualism and SRS may serve as one step toward, rather than as the
conclusion of, construction of a person's gender identity.
PMID- 28403324
TI - Screening and diagnosing postpartum depression: when and how?
AB - Introduction:: Prevalence rates of postpartum depression (PPD) vary widely,
depending on the methodological parameters used in studies: differences in study
populations, diagnostic methods, and postpartum time frame. There is also no
consensus on the ideal time to perform screening, on whether PPD can only be
diagnosed in the early postnatal period, or on how soon after a delivery
depression may be related to it. Objective:: To review which instruments have
been used over recent years to screen and diagnose PPD and the prevailing periods
of diagnosis. Methods:: Only articles published within 5 years and related
exclusively to screening and diagnosis were selected. The sample comprised 22
articles. Results:: The Edinburgh Posnatal Depression Scale (EPDS) was the most
common screening tool, used in 68% of the sample (15 articles), followed by the
Beck Depression Inventory (BDI-II) (27%, 6 articles), and the Patient Health
Questionnaire-9 (PHQ-9) (18%, 4 articles). Screening time frame was reported in
21/22 articles: 0 to 3 months postpartum in 9 (43%), up to 6 months in 4 (19%),
and up to 12 months or more in 8 (38%). In short, 13 articles screened during the
first 6 months (59%) while only 8 (36%) screened up to 1 year. Conclusion:: The
most frequent PPD diagnosis tool was the EPDS, but other scales were also used.
The most common period for diagnosis was up to 3 months postpartum. However, some
researchers diagnosed PPD 12 months or more postpartum. Greater standardization
of parameters for investigation of this disease is needed.
PMID- 28403325
TI - Bitemporal ultra-brief pulse electroconvulsive therapy for the treatment of
neuroleptic malignant syndrome in a first psychotic episode: a case report.
PMID- 28403327
TI - Internal control for real-time polymerase chain reaction based on MS2
bacteriophage for RNA viruses diagnostics.
AB - BACKGROUND: Real-time reverse transcription polymerase chain reaction (RT-PCR) is
routinely used to detect viral infections. In Brazil, it is mandatory the use of
nucleic acid tests to detect hepatitis C virus (HCV), hepatitis B virus and human
immunodeficiency virus in blood banks because of the immunological window. The
use of an internal control (IC) is necessary to differentiate the true negative
results from those consequent from a failure in some step of the nucleic acid
test. OBJECTIVES: The aim of this study was the construction of virus-modified
particles, based on MS2 bacteriophage, to be used as IC for the diagnosis of RNA
viruses. METHODS: The MS2 genome was cloned into the pET47b(+) plasmid,
generating pET47b(+)-MS2. MS2-like particles were produced through the synthesis
of MS2 RNA genome by T7 RNA polymerase. These particles were used as non
competitive IC in assays for RNA virus diagnostics. In addition, a competitive
control for HCV diagnosis was developed by cloning a mutated HCV sequence into
the MS2 replicase gene of pET47b(+)-MS2, which produces a non-propagating MS2
particle. The utility of MS2-like particles as IC was evaluated in a one-step
format multiplex real-time RT-PCR for HCV detection. FINDINGS: We demonstrated
that both competitive and non-competitive IC could be successfully used to
monitor the HCV amplification performance, including the extraction, reverse
transcription, amplification and detection steps, without compromising the
detection of samples with low target concentrations. In conclusion, MS2-like
particles generated by this strategy proved to be useful IC for RNA virus
diagnosis, with advantage that they are produced by a low cost protocol. An
attractive feature of this system is that it allows the construction of a
multicontrol by the insertion of sequences from more than one pathogen,
increasing its applicability for diagnosing different RNA viruses.
PMID- 28403329
TI - Longevity of metal-ceramic crowns cemented with self-adhesive resin cement: a
prospective clinical study
AB - Resin cements are often used for single crown cementation due to their physical
properties. Self-adhesive resin cements gained widespread due to their simplified
technique compared to regular resin cement. However, there is lacking clinical
evidence about the long-term behavior of this material. The aim of this
prospective clinical trial was to assess the survival rates of metal-ceramic
crowns cemented with self-adhesive resin cement up to six years. One hundred and
twenty-nine subjects received 152 metal-ceramic crowns. The cementation
procedures were standardized and performed by previously trained operators. The
crowns were assessed as to primary outcome (debonding) and FDI criteria.
Statistical analysis was performed using Kaplan-Meier statistics and descriptive
analysis. Three failures occurred (debonding), resulting in a 97.6% survival
rate. FDI criteria assessment resulted in scores 1 and 2 (acceptable clinical
evaluation) for all surviving crowns. The use of self-adhesive resin cement is a
feasible alternative for metal-ceramic crowns cementation, achieving high and
adequate survival rates.
PMID- 28403330
TI - Dental Management Survey Brazil (DMS-BR): creation and validation of a management
instrument
AB - Questionnaires for the assessment of knowledge and self-perception can be useful
to diagnose what a dentist knows about management and administration. The aim of
the present study was to create and validate the Dental Management Survey Brazil
(DMS-BR) scale, based on meetings with experts in the field. After having
elaborated the first version, 10 audits were performed in dental offices in order
to produce the final version, which included nine dimensions: location, patient,
finance, marketing, competition, quality, staff, career, and productivity. The
accuracy of the instrument was measured by intrarater and interrater reliability.
In the validation phase, 247 Brazilian dentists answered a web-based
questionnaire. The data were processed using Stata 13.0 and the significance
level was set at 95%. The instrument had intrarater and interrater reliability
(ICC-0.93 and 0.94). The overall average of respondents for the DMS-BR scale was
3.77 (SD = 0.45). Skewness and kurtosis were below absolute values 3 and 7,
respectively. Internal validity measured by Cronbach's alpha was 0.925 and the
correlation of each dimension with the final result of the DMS-BR ranged between
0.606 and 0.810. Correlation with the job satisfaction scale was 0.661. The SEM
data ranged between 0.80 and 0.56. The questionnaire presented satisfactory
indicators of dentists' self-perception about management and administration
activities.
PMID- 28403331
TI - Effects of avocado/soybean unsaponifiables (ASU) on the treatment of ligature
induced periodontitis in rats
AB - The purpose of this study is to evaluate the effect of the avocado/soybean
unsaponifiables (ASU) on the treatment of induced periodontitis in rats.
Periodontitis was induced in 84 rats via ligature placement around the second
upper molar, which was removed after 7 days, and scaling and root planning (SRP)
was performed at this time. Subsequently, the rats were randomly allocated to
four groups with 21 animals each: One SRP group in which saline solution was
administered (SS), and three groups in which ASU was administered (0.6 g/kg/day),
beginning either 7 days before the induction of periodontitis (SRP/ASU-7), on the
day of periodontitis induction (SRP/ASU0), or on the day of treatment
(SRP/ASU+7). ASU and SS were administered daily by gavage until the sacrifice of
the animals (7, 15, and 30 days after SRP). The % bone in the furcation area was
evaluated by histomorphometry and micro-CT. The expression of proteins (TRAP,
RANKL, and alkaline phosphatase) and mRNA (IL-1beta, TNF-alpha, IL-6, RANKL, and
alkaline phosphatase) were evaluated by immunohistochemistry and qPCR. The
SRP/ASU+7 group presented a higher percentage of bone fill in the furcation area
and higher expression of alkaline phosphatase than in the SRP group (at 7 and 30
days, respectively). The SRP/ASU0 and SRP/ASU+7 groups presented lower expression
levels of RANKL mRNA than the SRP and SRP/ASU-7 groups at 15 days. ASU
administration on the day of the SRP treatment of the ligature-induced
periodontitis promoted subtle beneficial effects on periodontal repair following
the treatment of induced periodontitis within the experimental period of 7 days.
PMID- 28403332
TI - Influence of root dentin treatment on the push-out bond strength of fibre
reinforced posts
AB - This study evaluates the influence of root dentin treatment with NaOCl alone and
combined with EDTA, with and without ultrasound activation, on the push-out bond
strength (BS) of fiber-reinforced posts in weakened roots, cemented with RelyX or
Panavia. The root canals of 42 maxillary canines were instrumented with Reciproc
and 2.5% NaOCl. In the coronal 12mm of all canals, experimental weakening of the
roots was produced by reducing dentin thickness with 2.44mm diameter diamond
burs. The roots were assigned to 3 groups (n = 14) according to root dentin
treatment: 2.5% NaOCl; 2.5% NaOCl + 17% EDTA; and 2.5% NaOCl + 17% EDTA, with
solutions agitated using passive ultrasonic irrigation. After cementation of the
fiber-reinforced posts the roots were divided in thirds. The first slice of each
third was used for the push-out BS test, the second slice for confocal laser
scanning microscopy and dentin microhardness (Knoop) analysis. Data were analysed
by a two-way ANOVA and Tukey test (a = 0.05). NaOCl + EDTA provided highest BS
values than NaOCl (p < 0.0001). Specimens cemented with Panavia presented
significantly higher BS than those with RelyX in the three root thirds (p <
0.0001). The highest BS values occurred in the cervical third (p < 0.001).
Ultrasound-activated NaOCl + EDTA promoted the greatest reduction in dentin
microhardness, followed by NaOCl/EDTA and NaOCl. Ultrasonic activation of NaOCl
and EDTA reduced root dentin microhardness, but did not improve the push-out BS
of resin-based cements. Panavia presented higher BS than RelyX. RelyX was not
influenced by the root dentin treatment protocols.
PMID- 28403333
TI - Assessment of risk of falls in elderly living at home.
AB - Objective: to assess the risk of falls in elderly, by comparing the
sociodemographic and cognitive factors, history of falls and self-reported
comorbidities. Method: cross-sectional and quantitative study with 240 elderly.
Data were collected based on the social profile, through the instrument of risk
of falls and assessment of falls, by univariate analysis, bivariate and multiple
logistic regression. The Statistical Package for the Social Sciences (SPSS)
version 19 was used for statistical analysis. Results: there was a significant
association of the risk of falls, as measured by the Fall Risk Score, with sex
(<0.001), age (0.054), cognitive status (<0.001) and history of falls (<0.001).
All variables were statistically significant and contributed to the occurrence of
falls. In logistic regression, the variables that showed association with risk of
falls were: fall, with whom they live, hypertension and visual impairment.
Conclusion: female gender, older elderly (over 80 years old), with low cognitive
status and occurrence of previous falls in the last six months are factors that
increase the prevalence of falls. In logistic regression, the variables that were
associated with risk of falls were: fall, with whom they live, visual impairment
and rheumatologic diseases.
PMID- 28403334
TI - Patient Safety Incidents and Nursing Workload.
AB - Objective: to identify the relationship between the workload of the nursing team
and the occurrence of patient safety incidents linked to nursing care in a public
hospital in Chile. Method: quantitative, analytical, cross-sectional research
through review of medical records. The estimation of workload in Intensive Care
Units (ICUs) was performed using the Therapeutic Interventions Scoring System
(TISS-28) and for the other services, we used the nurse/patient and nursing
assistant/patient ratios. Descriptive univariate and multivariate analysis were
performed. For the multivariate analysis we used principal component analysis and
Pearson correlation. Results: 879 post-discharge clinical records and the
workload of 85 nurses and 157 nursing assistants were analyzed. The overall
incident rate was 71.1%. It was found a high positive correlation between
variables workload (r = 0.9611 to r = 0.9919) and rate of falls (r = 0.8770). The
medication error rates, mechanical containment incidents and self-removal of
invasive devices were not correlated with the workload. Conclusions: the workload
was high in all units except the intermediate care unit. Only the rate of falls
was associated with the workload.
PMID- 28403335
TI - Auriculotherapy to reduce anxiety and pain in nursing professionals: a randomized
clinical trial.
AB - Objectives:: to evaluate the effectiveness of the auricular protocol (APPA) in
reducing pain and anxiety and improving the quality of life of the nursing staff
of a hospital. Method:: randomized clinical trial with an initial sample of 180
professionals divided into 4 groups Control (G1), Seed (G2), Needle (G3) and Tape
(G4). The evaluation instruments were the State-Trait Anxiety Inventory, Pain
Visual Analog Scale and Quality of Life instrument, applied at the start and
after five and 10 sessions (five weeks). Descriptive statistics, analysis of
variance (ANOVA) and Cohen's d Index were used in the analysis. Results:: there
was a statistical difference (p < 0.05) for anxiety according to the repeated
measures ANOVA, with better results for the G3 in the final assessment (Cohen's d
index 1.08/17% reduction). There was a reduction of pain of 36% in G3 and 24% in
G2 and a 13% increase in the mental aspect of quality of life for the G3,
although without statistical significance. Conclusion:: the APPA protocol reduced
the anxiety levels of nursing staff after 10 sessions. Further studies are,
however, suggested with new populations and in different contexts so that the
results can be confirmed. RBR-5pc43m. Objetivos:: avaliar a efetividade do
protocolo auricular para reducao de ansiedade, dor (APPA) e melhoria de qualidade
de vida em equipe de Enfermagem de um hospital. Metodo:: ensaio clinico
randomizado com amostra inicial de 180 profissionais divididos em 4 grupos
Controle (G1), Semente (G2), Agulha (G3) e Fita Adesiva (G4). Os instrumentos de
avaliacao foram o Inventario de Ansiedade Traco-Estado, Escala Visual Analogica
de dor e instrumento de Qualidade de Vida, aplicados no inicio, depois de cinco e
10 sessoes (cinco semanas). Na analise utilizou-se a estatistica descritiva, a
analise de variancia (ANOVA) e o Indice d de Cohen. Resultados:: houve diferenca
estatistica (p < 0,05) para a ansiedade segundo ANOVA de medidas repetidas, com
melhores resultados para o G3 na ultima avaliacao (indice d de Cohen 1,08/17% de
reducao). Houve reducao de 36% no G3, 24% no G2 para a dor e 13% de aumento no
nivel mental de qualidade de vida para o G3, embora sem diferencas estatisticas.
Conclusao:: o protocolo APPA reduziu os niveis de ansiedade em equipe de
enfermagem depois de 10 sessoes. Mas, sugerem-se mais estudos com novas
populacoes e em diferentes contextos para que os resultados se confirmem. RBR
5pc43m. Objetivos:: evaluar la efectividad del protocolo auricular para reduccion
de ansiedad, dolor (APPA) y mejoria de calidad de vida, en equipo de enfermeria
de un hospital. Metodo:: ensayo clinico aleatorizado con muestra inicial de 180
profesionales divididos en 4 grupos: Control (G1), Semilla (G2), Aguja (G3) y
Cinta Adhesiva (G4). Los instrumentos de evaluacion fueron el Inventario de
Ansiedad Rasgo-Estado, la Escala Visual Analogica de Dolor y el instrumento de
Calidad de Vida, aplicados en el inicio, y despues de cinco y 10 sesiones (cinco
semanas). En el analisis se utilizo la estadistica descriptiva, la analisis de
variancia (ANOVA) y el Indice d de Cohen. Resultados:: hubo diferencia
estadistica (p < 0,05) para la ansiedad segun ANOVA de medidas repetidas, con
mejores resultados para el G3 en la ultima evaluacion (indice d de Cohen 1,08/17%
de reduccion). Hubo reduccion de 36% en el G3, 24% en el G2 para el dolor y 13%
de aumento en el nivel mental de calidad de vida para el G3, a pesar de que sin
diferencias estadisticas. Conclusion:: el protocolo APPA redujo los niveles de
ansiedad en el equipo de enfermeria despues de 10 sesiones. Se sugiere realizar
mas estudios con nuevas poblaciones y en diferentes contextos para que los
resultados puedan ser confirmados. RBR-5pc43m.
PMID- 28403336
TI - Attitude and knowledge about foot health: a spanish view.
AB - Objective:: to explore attitudes towards patients' self-reported data about foot
health-related beliefs from a behavioural and attitudinal perspective. Methods::
a sample of 282 participants of a mean age of 39.46 +/- 16.026 came to a health
centre where self-reported demographic, clinical characteristics and beliefs
relating to foot health data were registered, informants' completed all the
stages of the research process. Results:: the results of the analysis revealed an
8-factor factorial structure based on (1) podiatric behaviours, (2) the intention
to carry out protective behaviour, (3) attitudinal beliefs, (4) normative
beliefs, (5) needs, (6) apathy, (7) self-care, and (8) the general perception of
foot health. They all explained 62.78% of the variance, and were considered as
independent variables in a regression analysis to determine which provided the
best explanations for the importance attributed to foot health. Conclusions:: the
participants in the study revealed a positive attitude in relation to foot health
care and responsible behaviour. Objetivo:: explorar as atitudes em relacao aos
dados auto-relatados dos pacientes sobre crencas relacionadas a saude do pe,
desde uma perspectiva comportamental e atitudinal. Metodos:: uma amostra de 282
participantes com idade media de 39,46 +/- 16,026 chegaram a um centro de saude
onde foram registradas caracteristicas demograficas, clinicas e crencas auto
relatadas referentes a dados de saude do pe, os quais completaram todas as fases
do processo de pesquisa. Resultados:: os resultados da analise revelaram uma
estrutura fatorial de 8 fatores baseada em (1) comportamentos podiatricos, (2) a
intencao de realizar comportamentos protetores, (3) crencas atitudinais, (4)
crencas normativas, (6) apatia, (7) autocuidado, e (8) a percepcao geral da saude
do pe. Todos eles explicaram 62,78% da variancia e foram considerados como
variaveis independentes em uma analise de regressao para determinar quais
forneceram as melhores explicacoes para a importancia atribuida a saude do pe.
Conclusoes:: os participantes do estudo revelaram uma atitude positiva em relacao
a saude do pe e comportamento responsavel. Objetivo:: explorar las actitudes
relacionadas con datos autoinformados sobre las creencias de la salud del pie
desde una perspectiva actitudinal. Metodo:: una muestra de 282 participantes edad
media 39.46 +/- 16.026 acudieron a un centro de salud donde se registraron datos
autoinformados de las caracteristicas demograficas, caracteristicas clinicas y
creencias relacionadas con la salud del pie, completandose todas las etapas del
proceso de investigacion. Resultados:: los resultados del analisis revelaron una
estructura factorial de 8 factores basado en (1) conductas podologicas, (2) la
intencion de llevar a cabo una conducta de proteccion, (3) las creencias
actitudinales, (4) las creencias normativas, (5) las necesidades, (6) la apatia,
(7) el autocuidado, y (8) la percepcion general de salud podal. Todos ellos
explicaron un 62,78% de la varianza, y fueron considerados como variables
independientes en una ecuacion de regresion para determinar cuales de ellos
explicaban mejor la importancia atribuida a la salud del pie. Conclusiones:: los
participantes en el estudio revelaron una actitud positiva en relacion al cuidado
de la salud del pie y al comportamiento responsable.
PMID- 28403337
TI - Assessment of the nursing care product (APROCENF): a reliability and construct
validity study.
AB - Objectives: to verify the reliability and construct validity estimates of the
"Assessment of nursing care product" scale (APROCENF) and its applicability.
Methods: this validation study included a sample of 40 (inter-rater reliability)
and 172 (construct validity) assessments performed by nurses at the end of the
work shift at nine inpatient services of a teaching hospital in the Brazilian
Southeast. The data were collected between February and September/2014 with
interruptions. Cronbach's alpha and Spearman's correlation coefficients were
calculated, as well as the intraclass correlation and the weighted kappa index
(inter-rater reliability). Exploratory factor analysis was used with principal
component extraction and varimax rotation (construct validity). Results: the
internal consistency revealed an alpha coefficient of 0.85, item-item correlation
ranging between 0.13 and 0.61 and item-total correlation between 0.43 and 0.69.
Inter-rater equivalence was obtained and all items evidenced significant factor
loadings. Conclusion: this research evidenced the reliability and construct
validity of the scale to assess the nursing care product. Its application in
nursing practice permits identifying improvements needed in the production
process, contributing to management and care decisions.
PMID- 28403338
TI - Needs of family caregivers in home care for older adults.
AB - Objective: to reveal the felt and normative needs of primary family caregivers
when providing instrumental support to older adults enrolled in a Home Care
Program in a Primary Health Service in the South of Brazil. Methods: using
Bradshaw's taxonomy of needs to explore the caregiver's felt needs (stated needs)
and normative needs (defined by professionals), a mixed exploratory study was
conducted in three steps: Descriptive quantitative phase with 39 older adults and
their caregiver, using a data sheet based on patient records; Qualitative
exploratory phase that included 21 caregiver interviews, analyzed by content
analysis; Systematic observation, using an observation guide with 16 caregivers,
analyzed by descriptive statistics. Results: the felt needs were related to
information about instrumental support activities and subjective aspects of care.
Caregivers presented more normative needs related to medications care.
Conclusion: understanding caregivers' needs allows nurses to plan interventions
based on their particularities.
PMID- 28403339
TI - Effective Universal Coverage of Diabetes Mellitus Type 2 in Chile.
AB - Objective: determine the prevalence of Effective Universal Coverage of Diabetes
Mellitus Type 2 in Chile and its relation with the variables: Health Care
Coverage of Diabetes Mellitus Type 2; Average of diabetics with metabolic control
in 2011-2013; Mortality Rate for Diabetes Mellitus; and Percentage of nurses
participating in the Cardiovascular Health Program. Method: cross-sectional
descriptive study with ecological components that uses documentary sources of the
Ministry of Health. It was established that there is correlation between the
Universal Effective Coverage of Diabetes Mellitus Type 2 and the independent
variables; it was applied the Pearson Coefficient, being significant at the 0.05
level. Results: in Chile Universal Health Care Coverage of Diabetes Mellitus Type
2 (HbA1c<7% estimated population) is less than 20%; this is related with
Mortality Rate for Diabetes Mellitus and Percentage of nurses participating in
the Cardiovascular Health Program, being significant at the 0.01 level.
Conclusion: effective prevalence of Universal Health Coverage of Diabetes
Mellitus Type 2 is low, even though some regions stand out in this research and
in the metabolic control of patients who participate in health control program;
its relation with percentage of nurses participating in the Cardiovascular Health
Program represents a challenge and an opportunity for the health system.
PMID- 28403340
TI - Fertility rates and perinatal outcomes of adolescent pregnancies: a retrospective
population-based study.
AB - Objective: analyze trends in fertility rates and associations with perinatal
outcomes for adolescents in Santa Catarina, Brazil. Methods: a population-based
study covering 2006 to 2013 was carried out to evaluate associations between
perinatal outcomes and age groups, using odds ratios, and Chi-squared tests.
Results: differences in the fertility rate among female adolescents across
regions and time period were observed, ranging from 40.9 to 72.0 per 1,000 in
mothers aged 15-19 years. Adolescents had fewer prenatal care appointments than
mothers >=20 years, and a higher proportion had no partner. Mothers aged 15-19
years were more likely to experience preterm birth (OR:1.1; CI:1.08-1.13;
p<0.001), have an infant with low birthweight (OR:1.1; CI:1.10-1.15; p<0.001) and
low Apgar score at 5 minutes (OR:1.4; CI:1.34-1.45; p<0.001) than mothers >=20
years, with the odds for adverse outcomes greater for those aged 10-14 years.
Conclusion: this study provides evidence of fertility rates among adolescents
remaining higher in regions of social and economic deprivation. Adolescent
mothers and their infants more likely to experience adverse perinatal outcomes.
Nurses, public health practitioners, health and social care professionals and
educators need to work collaboratively to better target strategies for
adolescents at greater risk; to help reduce fertility rates and improve outcomes.
PMID- 28403341
TI - Anatomo-radiological correlation using 18-FDG-PET in abdominal sepsis model in
rats. A preliminary study.
AB - Purpose:: To examine a correlation of micro-PET images with photographic images
of the digestive organs in abdominal sepsis model. Methods:: Male Wistar rats
weighing 265+/-18g were used. Abdominal sepsis was induced by ligature and cecal
puncture. Micro-PET Images from abdominal cavity septic foci were obtained using
18-Fluoro-deoxyglucose, looking for a correlation with photographic images of
abdominal cavity organs. Pearson's correlation test was used. Results:: The mean
standard uptake values (SUV) and lesion areas were 2.58+/-0.63SUVbwg/ml and
546.87+/-300.95mm2, respectively. There was a strong positive correlation between
the two variables (r=0.863, p=0.137), which resulted in a coefficient of
determination r2?0.75, meaning that 75% of SUV variation is explained by the
lesion areas of digestive organs. Conclusion: : Micro-PET allows high throughput
assessment of lesion count and volume in pre-clinical rat model of CPL abdominal
sepsis.
PMID- 28403342
TI - Tissue sulfomucin and sialomucin content in colon mucosa without intestinal
transit subjected to intervention with Curcuma longa (curcumin).
AB - Purpose:: To measure the tissue sulfomucin and sialomucin content of the colon
mucosa without fecal flow, subjected to intervention with curcumin, and the
influence of the concentration used and the intervention time. Methods:: Thirty
six rats were subjected to proximal right colostomy and distal mucous fistula.
They were divided into two groups according to whether sacrifice was performed
two or four weeks after the intervention. Each group was divided into three
subgroups according to the enema applied daily: saline alone; curcumin at 50
mg/kg/day or curcumin at 200 mg/kg/day. Acid mucins were diagnosed using the
Alcian blue technique. The mucin content was quantified by means of computer
assisted image analysis. The significance level of 5% was used throughout (p <
0.05). Results:: There were dose-related increases in the quantities of
sulfomucins in the animals subjected to interventions with curcumin, both after
two weeks (p < 0.00001) and after four weeks (p < 0.00001). There were increases
in sialomucin quantity that were concentration-related (p < 0.00001) and time
related (p < 0.00001). Conclusion:: Curcumin enemas increase the quantity of acid
mucins in the intestinal flow in the excluded colon, with dose and time
dependency.
PMID- 28403343
TI - Lycopene and resveratrol pretreatment did not interfere with the liver of
hepatectomized rats.
AB - Purpose:: To investigate the effects of lycopene and resveratrol pretreatment on
hepatic hyperplasia in partially hepatectomized rats. Methods:: The lycopene
group and the resveratrol group received 40 mg/kg/day of lycopene or resveratrol,
respectively (dissolved in olive oil or in saline solution, respectively) and
administered via a gastric tube for 30 days. The partially hepatectomzed (PH)
control groups received saline or olive oil via a gastric tube for 30 days,
respectively, and the normal control group received no treatment. Liver tissue
and intracardiac blood samples were obtained 24, 36 or 48 h after PH. Results::
No areas of fibrosis were detected. No significant changes in mitotic index, in
the number of apoptosis events or in aspartate aminotransferase and alanine
aminotransferase levels were observed. Conclusions:: Lycopene and resveratrol
pretreatment did not interfere on hepatic hyperplasia in partially hepatectomized
rats.
PMID- 28403344
TI - Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion
induced renal injury in transiently hyperglycemic rats.
AB - Purpose:: To investigate the effects of cyclosporine A on renal ischemia
reperfusion injury during transient hyperglycemia in rats. Methods: : In a model
of ischemia-reperfusion-induced renal injury and transiently induced
hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats
were anesthetized with either isoflurane or propofol and received intravenous
cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups
were isoflurane and propofol sham groups and isoflurane and propofol ischemia
reperfusion-induced renal injury. Renal tubular cell viability was quantitatively
assessed by flow cytometry after cell culture and classified as early apoptosis,
necrotic cells, and intact cells. Results: : Early apoptosis was significantly
higher in isoflurane and propofol anesthetized animals subjected to renal
ischemia-reperfusion injury when compared to both cyclosporine A treated and sham
groups. Necrosis percentage was significantly higher in propofol-anesthetized
animals subjected to renal ischemia-reperfusion injury. The percentage of intact
cells was lower in both, isoflurane and propofol anesthetized animals subjected
to renal ischemia-reperfusion injury. Conclusion: : In a model of ischemia
reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five
minutes before renal reperfusion in rats with acute-induced hyperglycemia under
either isoflurano or propofol anesthesia, attenuated early apoptosis and
preserved viability in renal tubular cells, regardless of the anesthetic used.
PMID- 28403345
TI - Effects of hypertonic saline solution associated to remote ischemic
perconditioning in kidney ischemia/reperfusion injury in rats.
AB - Purpose: : To evaluate the effects of hypertonic saline solution associated to
remote ischemic perconditioning in renal ischemia/reperfusion injury in rats.
Methods: : Twenty five male rats (Wistar) underwent right nephrectomy and were
distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R)
with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per)
with three cycles of 10 minutes of I/R performed during kidney ischemia;
Hypertonic saline solution group (HSS) treated with hypertonic saline solution
(4ml/kg); remote ischemic perconditioning + Hypertonic saline solution group
(Per+HSS) with both treatments. After reperfusion, blood samples were collected
for BUN and creatinine serum levels analyzes. TBARS were evaluated in plasma and
renal tissue to assess oxidative stress. Kidney histopathological examination
were performed. Results: : Per+HSS group showed a lower degree of renal
dysfunction in relation to I/R group, whereas the technique of remote ischemic
perconditioning isolated or associated with saline solution significantly reduced
oxidative stress and histological damage. Conclusion: : Remote ischemic
perconditioning associated or not to saline solution promoted reduction of acute
renal injury induced by ischemia/reperfusion.
PMID- 28403346
TI - The effects of ozone on bacterial growth and thiol-disulphide homeostasis in
vascular graft infection caused by MRSA in rats.
AB - Purpose:: To investigate the microbiological, inflammatory and oxidant effects of
adjuvant ozone administration in experimental rat vascular graft infection model
which has not been previously investigated. Methods:: Forty adult Wistar rats
were divided into Sham, Control, Vancomycin, Ozone, Vancomycin+Ozone groups.
Grafts were inoculated with Methicillin-resistant Staphylococcus aureus (MRSA)
strain and implanted subcutaneously. Rats were treated intraperitoneally with
ozone and /or intramuscularly with vancomycin for 10 days. Grafts were evaluated
by quantitative bacterial cultures. Blood samples were harvested for
determination of thiol-disulphide and cytokine profiles. Results:: There was no
significant difference in bacterial counts between Control and Ozone Groups. In
the Ozone Group median colony count was significantly higher than the Vancomycin
and Vancomycin+Ozone Groups. Total thiol and disulphide levels increased and
disulphide/native thiol and disulphide/total thiol ratios decreased in Ozone
Group significantly. Albumin levels decreased significantly in Vancomycin and
Vancomycin+Ozone Groups compared to the Sham Group. IL-1 and TNF-alpha levels
significantly increased in infected rats. Decreased levels of VEGF due to
infection reversed by ozone therapy in control and vancomycin groups.
Conclusions:: We didn't observe any benefit of the agent on MRSA elimination in
our model. Likewise, effects of ozone on thiol-disulphide homeostasis and
inflammatory cytokines were contradictory.
PMID- 28403347
TI - Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative
stress in kidney ischemia/reperfusion injury in rats.
AB - Purpose: : To evaluate the effects of tramadol hydrochloride associated to remote
ischemic perconditioning on oxidative stress. Methods: : Twenty five male rats
(Wistar) underwent right nephrectomy and were distributed into five groups: Sham
group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia;
Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of
I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol
hydrochloride (40mg/kg); remote ischemic perconditioning + Tramadol group (Per+T)
with both treatments. Oxidative stress was assessed after 24 hours of
reperfusion. Results: : Statistical differences were observed in MDA levels
between I/R group with all groups (p<0.01), in addition there was difference
between Tramadol with Sham, Per and Per+T groups (p<0.05), both in plasma and
renal tissue. Conclusion: : Remote ischemic perconditioning was more effective
reducing renal ischemia-reperfusion injury than administration of tramadol or
association of both treatments.
PMID- 28403348
TI - Neonatal necrotizing enterocolitis rat model attenuated by a remote ischemic
preconditioning in the pregnant.
AB - Purpose:: To evaluate the effect of remote ischemic preconditioning (r-IPC)
administered to pregnant rats, in the ileum of newborn rats subjected to hypoxia
and reoxygenation. Methods: : We used three pregnant rats and their newborn rats
distributed in three groups: 1) Control (C) - Newborn rats born from a pregnant
rat which did not undergo any intervention; 2) Hypoxia-Reoxygenation (H/R) -
Newborn rats born from a pregnant rat which did not undergo any intervention, and
were subjected to hypoxia-reoxygenation; 3) Remote Ischemic Preconditioning (r
IPC) - newborn rats born from a pregnant rat which was subjected to remote
ischemic preconditioning twenty-four hours before giving birth and the newborn
rats were subjected to hypoxia-reoxygenation. Segments of ileum were prepared for
histological analysis by HE and immunohistochemistry by the Ki67 to evaluate cell
proliferation, crypt depth and villus height and evaluation of apoptosis by
cleaved caspase-3. Results: : The intensity of the lesions was lower in the r-IPC
than in the H/R group, showing significant difference (p<0.01). The r-IPC group
showed a higher proliferative activity compared to the H/R group (p<0.01), with
deeper crypts (r-IPC > H/R - p < 0.05), and higher villi, showing significant
difference (r-IPC > H/R - (p <0.01). The occurrence of apoptosis in the H/R group
was lower in comparison to groups C and r-IPC, with significant difference (H/R <
r-IPC; p<0.05). Conclusion:: The remote ischemic preconditioning applied to the
pregnant rat protected the ileum of newborn rats subjected to hypoxia and
reoxygenation, with decreased intensity of the lesions in the ileum mucosa and
preservation of proliferative activity, keeping the villus height and crypt depth
similar to group C.
PMID- 28403349
TI - Analysis of gene expression EGFR and KRAS, microRNA-21 and microRNA-203 in
patients with colon and rectal cancer and correlation with clinical outcome and
prognostic factors.
AB - Purpose:: To evaluate the expression of EGFR, KRAS genes, microRNAs-21 and 203 in
colon and rectal cancer samples, correlated with their age at diagnosis,
histological subtype, value of pretreatment CEA, TNM staging and clinical
outcome. Methods: : Expression of genes and microRNAs by real time PCR in tumor
and non-tumor samples obtained from surgical treatment of 50 patients. Results: :
An increased expression of microRNAs-21 and 203 in tumor samples in relation to
non-tumor samples was found. There was no statistically significant difference
between the expression of these genes and microRNAs when compared to age at
diagnosis and histological subtype. The EGFR gene showed higher expression in
relation to the value of CEA diagnosis. The expression of microRNA-203 was
progressively lower in relation to the TNM staging and was higher in the patient
group in clinical remission. Conclusions: : The therapy of colon and rectum
tumors based on microRNAs remains under investigation reserving huge potential
for future applications and clinical interventions in conjunction with existing
therapies. We expect, based on the exposed data, to stimulate the development of
new therapeutic possibilities, making the treatment of these tumors more
effective.
PMID- 28403350
TI - Improving reproducibility and external validity. The role of standardization and
data reporting of laboratory rat husbandry and housing.
AB - Purpose: : To identify the most relevant flaws in standardization in husbandry
practices and lack of transparency to report them. This review proposes some
measures in order to improve transparency, reproducibility and eventually
external validity in experimental surgery experiments with rat model. Methods: :
We performed a search of scientific articles in PUBMED data base. The survey was
conducted from august 2016 to January 2017. The keywords used were
"reproducibility", "external validity", "rat model", "rat husbandry", "rat
housing", and the time frame was up to January 2017. Articles discarded were the
ones which the abstract or the key words did not imply that the authors would
discuss any relationship of husbandry and housing with the reproducibility and
transparency of reporting animal experiment. Reviews and papers that discussed
specifically reproducibility and data reporting transparency were laboriously
explored, including references for other articles that could fulfil the inclusion
criteria. A total of 246 articles were initially found but only 44 were selected.
Results: : Lack of transparency is the rule and not the exception when reporting
results with rat model. This results in poor reproducibility and low external
validity with the consequence of considerable loss of time and financial
resources. There are still much to be done to improve compliance and adherence of
researchers, editors and reviewers to adopt guidelines to mitigate some of the
challenges that can impair reproducibility and external validity. Conclusions: :
Authors and reviewers should avoid pitfalls of absent, insufficient or inaccurate
description of relevant information the rat model used. This information should
be correctly published or reported on another source easily available for
readers. Environmental conditions are well known by laboratory animal personnel
and are well controlled in housing facilities, but usually neglected in
experimental laboratories when the rat model is a novelty for the researcher.
PMID- 28403351
TI - Short-term transcutaneous electrical nerve stimulation reduces pain and improves
the masticatory muscle activity in temporomandibular disorder patients: a
randomized controlled trial.
AB - Objective: To investigate the short-term effect of transcutaneous electrical
nerve stimulation (TENS) by examining pain intensity, pressure pain threshold
(PPT) and electromyography (EMG) activity in patients with temporomandibular
disorder (TMD). Material and Methods: Forty patients with myofascial TMD were
enrolled in this randomized placebo-controlled trial and were divided into two
groups: active (n=20) and placebo (n=20) TENS. Outcome variables assessed at
baseline (T0), immediately after (T2) and 48 hours after treatment (T1) were:
pain intensity with the aid of a visual analogue scale (VAS); PPT of masticatory
and cervical structures; EMG activity during mandibular rest position (MR),
maximal voluntary contraction (MVC) and habitual chewing (HC). Two-way ANOVA for
repeated measures was applied to the data and the significance level was set at
5%. Results: There was a decrease in the VAS values at T1 and T2 when compared
with T0 values in the active TENS group (p<0.050). The PPT between-group
differences were significant at T1 assessment of the anterior temporalis and
sternocleidomastoid (SCM) and T2 for the masseter and the SCM (p<0.050). A
significant EMG activity reduction of the masseter and anterior temporalis was
presented in the active TENS during MR at T1 assessment when compared with T0
(p<0.050). The EMG activity of the anterior temporalis was significantly higher
in the active TENS during MVC at T1 and T2 when compared with placebo (p<0.050).
The EMG activity of the masseter and anterior temporalis muscle was significantly
higher in the active TENS during HC at T1 when compared with placebo (p<0.050).
Conclusions: The short-term therapeutic effects of TENS are superior to those of
the placebo, because of reported facial pain, deep pain sensitivity and
masticatory muscle EMG activity improvement.
PMID- 28403352
TI - Effects of grape seed extract on periodontal disease: an experimental study in
rats.
AB - Objective: This study aimed to demonstrate the effect of grape seed extract (GSE)
on periodontitis. Material and Methods: Ligature induced periodontitis was
created in 40 rats and they were assigned to four equal groups. One group was fed
laboratory diet (group A) while three groups received GSE additionally. Silk
ligatures were placed around the cervical area of the mandibular first molars for
four weeks to induce periodontitis. The GSE groups were reallocated regarding GSE
consumption as: for two weeks before ligation (group B; totally eight weeks),
from ligation to two weeks after removal of the ligature (group C; totally six
weeks), and for two weeks from ligature removal (group D; totally two weeks).
Sections were assessed histologically and immunohistochemically. Inflammatory
cell number (ICN), connective tissue attachment level (CAL), osteoclast density
(OD), IL-10 and TGF-beta stainings in gingival epithelium (GE), connective tissue
(GC), and periodontal ligament (PL) were used as the study parameters. Results:
Lower ICN, higher CAL, and lower OD were observed in the GSE groups (p<0.05). IL
10 was more intensive in the GSE groups and in the GEs (p<0.05). Group B showed
the highest IL-10 for PL (p<0.05). TGF-beta was higher in the GEs of all groups
(p<0.017). Conclusions: The results suggest anti-inflammatory activities of GSE,
but further investigations are needed for clarification of these activities.
PMID- 28403353
TI - Periodontitis and type 2 diabetes among women with previous gestational diabetes:
epidemiological and immunological aspects in a follow-up of three years.
AB - Objective: The aim of this study was to verify the incidence on the development
of type 2 diabetes in women with previous gestational diabetes with and without
periodontitis after a three-year time interval. Material and Methods: Initial
sample of this follow-up study consisted of 90 women diagnosed with gestational
diabetes who underwent periodontal examination. After three years, 49 women were
subjected to new periodontal examination and biological, behavioral, and social
data of interest were collected. Additionally, the quantification of the C
reactive protein in blood samples was performed. Fasting glucose and glycated
hemoglobin levels were requested. Saliva samples were collected for
quantification of interleukin 6 and 10, tumor necrosis factor alpha, matrix
metalloproteinase 2 and 9. Results: The incidence of type 2 diabetes mellitus was
18.4% and of periodontitis was 10.2%. There was no significant difference in the
incidence of type 2 diabetes mellitus among women with and without periodontitis.
It was observed impact of C-reactive protein in the development of type 2
diabetes mellitus. However, it was not observed impact of periodontitis on the
development of type 2 diabetes mellitus among women with previous gestational
diabetes. Conclusions: It was not observed impact of periodontitis on the
development of type 2 diabetes among women with previous gestational diabetes.
The impact of C-reactive protein in the development of type 2 diabetes mellitus
highlights the importance of an inflammatory process in the diabetes
pathogenesis.
PMID- 28403354
TI - Effects of radiant exposure values using second and third generation light curing
units on the degree of conversion of a lucirin-based resin composite.
AB - Objective: Using Fourier transform infrared analysis (FTIR) in vitro, the effects
of varying radiant exposure (RE) values generated by second and third generation
LED LCUs on the degree of conversion (DC) and maximum rate of polymerization
(Rpmax) of an experimental Lucirin TPO-based RC were evaluated. Material and
Methods: 1 mm or 2 mm thick silicon molds were positioned on a horizontal
attenuated total reflectance (ATR) unit attached to an infrared spectroscope. The
RC was inserted into the molds and exposed to varying REs (18, 36 and 56 J/cm2)
using second (Radii Plus, SDI) and third generation LED LCUs (Bluephase
G2/Ivoclar Vivadent) or a quartz tungsten based LCU (Optilux 501/SDS Kerr). FTIR
spectra (n=7) were recorded for 10 min (1 spectrum/s, 16 scans/spectrum,
resolution 4 cm-1) immediately after their application to the ATR. The DC was
calculated using standard techniques for observing changes in aliphatic to
aromatic peak ratios both prior to, and 10 min after curing, as well as during
each 1 second interval. DC and Rpmax data were analyzed using 3-way ANOVA and
Tukey's post-hoc test (p=0.05). Results: No significant difference in DC or Rpmax
was observed between the 1 mm or 2 mm thick specimens when RE values were
delivered by Optilux 501 or when the 1 mm thick composites were exposed to light
emitted by Bluephase G2, which in turn promoted a lower DC when 18 J/cm2 (13 s)
were delivered to the 2 mm thick specimens. Radii Plus promoted DC and Rpmax
values close to zero under most conditions, while the delivery of 56 J/cm2 (40 s)
resulted in low DC values. Conclusions: The third generation LCU provided an
optimal polymerization of Lucirin TPO-based RC under most tested conditions,
whereas the second generation LED-curing unit was useless regardless of the RE.
PMID- 28403355
TI - Human DNA extraction from whole saliva that was fresh or stored for 3, 6 or 12
months using five different protocols.
AB - Objective and Material and Methods: This study aimed to compare the quantity and
quality of human DNA extracted from saliva that was fresh or frozen for three,
six and twelve months using five different DNA extraction protocols: protocol 1 -
OrageneTM commercial kit, protocol 2 - QIAamp DNA mini kit, protocol 3 - DNA
extraction using ammonium acetate, protocol 4 - InstageneTM Matrix and protocol 5
- InstageneTM Matrix diluted 1:1 using proteinase K and 1% SDS. Briefly, DNA was
analyzed using spectrophotometry, electrophoresis and PCR. Results: Results
indicated that time spent in storage typically decreased the DNA quantity with
the exception of protocol 1. The purity of DNA was generally not affected by
storage times for the commercial based protocols, while the purity of the DNA
samples extracted by the noncommercial protocols typically decreased when the
saliva was stored longer. Only protocol 1 consistently extracted unfragmented DNA
samples. In general, DNA samples extracted through protocols 1, 2, 3 and 4,
regardless of storage time, were amplified by human specific primers whereas
protocol 5 produced almost no samples that were able to be amplified by human
specific primers. Depending on the protocol used, it was possible to extract DNA
in high quantities and of good quality using whole saliva, and furthermore, for
the purposes of DNA extraction, saliva can be reliably stored for relatively long
time periods. Conclusions: In summary, a complicated picture emerges when taking
into account the extracted DNA's quantity, purity and quality; depending on a
given researchers needs, one protocol's particular strengths and costs might be
the deciding factor for its employment.
PMID- 28403356
TI - Fluoxetine effects on periodontogenesis: histomorphometrical and
immunohistochemical analyses in rats.
AB - Objective: This study aimed to assess the effects of fluoxetine, a selective
serotonin reuptake inhibitor, on the formation of the periodontal ligament during
pregnancy and lactation in rat pups. Material and Methods: Twelve pregnant rats
of Wistar lineage were divided into four study groups. In the control group, 0.9%
sodium chloride solution was administered orally, throughout the entire period of
the 21 days of pregnancy (CG group) and in the CGL group, it was administrated
during pregnancy and lactation (from day 1 of pregnancy to the 21st day after
birth). Fluoxetine was administered orally at the dose of 20 mg/kg in a group
treated during pregnancy only (FG group), and during pregnancy and lactation (FGL
group). Histometrical, histochemical and immunohistochemical analysis of the
maxillary first molar periodontium region of the 24 rat pups was made under light
microscopy, and periodontal ligament collagen was qualitatively evaluated under a
polarizing light microscope. Results: The quantity of fibroblasts (p=0.006),
osteoblasts (p=0.027) and cementoblasts (p=0.001) was reduced in pups from the
rats that received fluoxetine during pregnancy and lactation. No alterations were
seen in the collagen fibers. Conclusion: These findings suggest that periodontal
tissue may be sensitive to fluoxetine, and its interference in reducing
periodontal cells depends on exposure time during lactation.
PMID- 28403357
TI - Local application of statins in the treatment of experimental periodontal disease
in rats.
AB - Objective: The objective of this study was to evaluate the local effects of
statins as adjuvants for treatment by scaling and root planing (SRP) of
periodontal disease induced in rats. Material and Methods: Ninety rats were used
in the present experiment. Periodontal disease was induced in all animals using a
cotton thread placed in the left first mandibular molar. After 7 days of
induction, the bandage was removed and the animals were divided into three
groups: 1) NT group (n=30), no treatment; 2) SRP group (n=30): SRP and irrigation
with control gel; 3) S group (n=30) - SRP and irrigation with Simvastatin. Ten
animals from each group were euthanized at 7, 15 and 30 days after treatment.
Gingival biopsy specimens were processed to analyze the expression of matrix
metalloproteinase 8 (MMP-8). The mandibles were removed and submitted to
radiographic and laboratory processing for histometric analysis. Results: The S
group showed a significantly lower expression of MMP-8 compared to NT and SRP
groups in all experimental periods. In the radiographic and histometric analyses
between the groups, S group showed a significantly lower bone loss (BL) compared
to NT and SRP groups in all experimental periods. Conclusions: Within the limits
of this study, it can be concluded that locally applied statin was effective as
an adjuvant treatment for SRP in rats with induced periodontal disease.
PMID- 28403359
TI - Oral mucosa: an alternative epidermic cell source to develop autologous dermal
epidermal substitutes from diabetic subjects.
AB - Objective: The aim of this study was to obtain autologous dermal-epidermal skin
substitutes from oral mucosa from diabetic subjects as a first step towards a
possible clinical application for cases of diabetic foot. Material and Methods:
Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group).
Epidermal cells were isolated and cultured using autologous fibrin to develop
dermal-epidermal in vitro substitutes by the air-liquid technique with autologous
human serum as a supplement media. Substitutes were immunocharacterized with
collagen IV and cytokeratin 5-14 as specific markers. A Student's t- test was
performed to assess the differences between both groups. Results: It was possible
to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects
and develop autologous dermal-epidermal skin substitutes using autologous serum
as a supplement. Differences in the expression of specific markers were observed
and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and
the collagen IV expression was higher in the diabetic substitutes when compared
with the healthy group, showing a significant difference. Conclusion: Cells from
oral mucosa could be an alternative and less invasive source for skin substitutes
and wound healing. A difference in collagen production of diabetic cells suggests
diabetic substitutes could improve diabetic wound healing. More research is
needed to determine the crosstalk between components of these skin substitutes
and damaged tissues.
PMID- 28403358
TI - Enhanced bioactive properties of BiodentineTM modified with bioactive glass
nanoparticles.
AB - Objective: To prepare nanocomposite cements based on the incorporation of
bioactive glass nanoparticles (nBGs) into BiodentineTM (BD, Septodent, Saint-Maur
des-Fosses Cedex, France) and to assess their bioactive properties. Material and
Methods: nBGs were synthesised by the sol-gel method. BD nanocomposites (nBG/BD)
were prepared with 1 and 2% nBGs by weight; unmodified BD and GC Fuji IX (GIC, GC
Corporation, Tokyo, Japan) were used as references. The in vitro ability of the
materials to induce apatite formation was assessed in SBF by X-ray diffraction
(XRD), attenuated total reflectance with Fourier transform infrared spectroscopy
(ATR-FTIR), and scanning electron microscopy (SEM) with energy dispersive X-ray
(EDX) analysis. BD and nBG/BD were also applied to dentine discs for seven days;
the morphology and elemental composition of the dentine-cement interface were
analysed using SEM-EDX. Results: One and two percent nBG/BD composites
accelerated apatite formation on the disc surface after short-term immersion in
SBF. Apatite was detected on the nBG/BD nanocomposites after three days, compared
with seven days for unmodified BD. No apatite formation was detected on the GIC
surface. nBG/BD formed a wider interfacial area with dentine than BD, showing
blockage of dentine tubules and Si incorporation, suggesting intratubular
precipitation. Conclusions: The incorporation of nBGs into BD improves its in
vitro bioactivity, accelerating the formation of a crystalline apatite layer on
its surface after immersion in SBF. Compared with unmodified BD, nBG/BD showed a
wider interfacial area with greater Si incorporation and intratubular
precipitation of deposits when immersed in SBF.
PMID- 28403360
TI - Influence of resin-modified glass ionomer and topical fluoride on levels of
Streptococcus mutans in saliva and biofilm adjacent to metallic brackets.
AB - Decalcification of enamel during fixed orthodontic appliance treatment remains a
problem. White spot lesions are observed in nearly 50% of patients undergoing
orthodontic treatment. The use of fluoride-containing orthodontic materials has
shown inconclusive results on their ability to reduce decalcification. The aims
of this investigation were to compare the levels of Streptococcus mutans (SM) in
saliva and biofilm adjacent to orthodontic brackets retained with a resin
modified glass ionomer cement (RMGIC) (Fuji ORTHO LC) and a light cured composite
resin (Transbond XT), and to analyze the influence of topical application of the
1.23% acidulated phosphate fluoride (APF) on SM counts. In a parallel study
design, two groups (n=14/15) were used with random allocation and high salivary
SM counts before treatment. Biofilm was collected from areas adjacent to the
brackets on teeth 13, 22, 33, and 41. Both saliva and biofilm were collected on
the 7th, 21st, 35th, and 49th days after appliance placement. Topical fluoride
application was carried out on the 35th day. Bonding with RMGIC did not alter SM
counts in saliva or biofilm adjacent to the brackets. On the other hand, the
biofilm adjacent to brackets retained with composite resin showed a significant
increase in SM counts along the trial period. Topical application of 1.23% APF
did not reduce salivary or biofilm SM counts regardless of the bonding material.
In conclusion, fluoride topical application did not show efficacy in reducing SM.
The use of RMGIC as bonding materials allowed a better control of SM cfu counts
in dental biofilm hindering the significant increase of these microorganisms
along the trial period, which was observed in the biofilm adjacent to the
composite material.
PMID- 28403361
TI - Effect of different composite core materials on fracture resistance of
endodontically treated teeth restored with FRC posts.
AB - Objective: This study evaluated the fracture resistance of endodontically treated
teeth restored with fiber reinforced composite posts, using three resin composite
core build-up materials, (Clearfil Photo Core (CPC), MultiCore Flow (MCF), and
LuxaCore Z-Dual (LCZ)), and a nanohybrid composite, (Tetric N-Ceram (TNC)).
Material and Methods: Forty endodontically treated lower first premolars were
restored with quartz fiber posts (D.T. Light-Post) cemented with resin cement
(Panavia F2.0). Samples were randomly divided into four groups (n=10). Each group
was built-up with one of the four core materials following its manufacturers'
instructions. The teeth were embedded in acrylic resin blocks. Nickel-Chromium
crowns were fixed on the specimens with resin cement. The fracture resistance was
determined using a universal testing machine with a crosshead speed of 1 mm/min
at 1350 to the tooth axis until failure occurred. All core materials used in the
study were subjected to test for the flexural modulus according to ISO 4049:2009.
Results: One-way ANOVA and Bonferroni multiple comparisons test indicated that
the fracture resistance was higher in the groups with CPC and MCF, which
presented no statistically significant difference (p>0.05), but was significantly
higher than in those with LCZ and TNC (p<0.05). In terms of the flexural modulus,
the ranking from the highest values of the materials was aligned with the same
tendency of fracture loads. Conclusion: Among the cores used in this study, the
composite core with high filler content tended to enhance fracture thresholds of
teeth restored with fiber posts more than others.
PMID- 28403362
TI - Effects of hyaluronic acid on bleeding following third molar extraction.
AB - Objective: To explore the effects of hyaluronic acid (HA) on bleeding and
associated outcomes after third molar extraction. Methods: Forty patients who had
undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA
was applied to the HA group (n=20) whereas a control group (n=20) was not
treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum
interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the
swelling extent were compared between the two groups. Results: HA did not
significantly affect gingival TF levels. Salivary TF levels increased
significantly 1 week after HA application but not in the control group. Neither
the VAS pain level nor MIO differed significantly between the two groups. The
swelling extent on day 3 and the bleeding time were greater in the HA group than
in the control group. Conclusions: Local injection of HA at 0.8% prolonged the
bleeding time, and increased hemorrhage and swelling in the early postoperative
period after third molar extractions.
PMID- 28403363
TI - Microbiological, lipid and immunological profiles in children with gingivitis and
type 1 diabetes mellitus.
AB - Objective: The aim of this study was to compare the prevalence of periodontal
pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes
children (DM) with those observed in children without diabetes (NDM), both with
gingivitis. Material and methods: Twenty-four DM children and twenty-seven NDM
controls were evaluated. The periodontal status, glycemic and lipid profiles were
determined for both groups. Subgingival samples of periodontal sites were
collected to determine the prevalence of periodontal microorganisms by PCR. Blood
samples were collected for IL-1-beta, TNF-alpha and IL-6 analysis using ELISA
kits. Results: Periodontal conditions of DM and NDM patients were similar,
without statistical differences in periodontal indices. When considering patients
with gingivitis, all lipid parameters evaluated were highest in the DM group;
Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the
periodontal sites of DM children. "Red complex" bacteria were detected in few
sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were
frequently found in both groups. Similar levels of IL-1-beta, TNF-alpha and IL-6
were detected in DM and NDM children. Conclusion: Clinical and immunological
profiles are similar between DM and NDM children. The presence of Capnocytophaga
sputigena and Capnocytophaga ochracea were associated with gingivitis in DM
children.
PMID- 28403364
TI - Diagnosis of alveolar and root fractures: an in vitro study comparing CBCT
imaging with periapical radiographs.
AB - Objective: To compare periapical radiograph (PR) and cone-beam computed
tomography (CBCT) in the diagnosis of alveolar and root fractures. Material and
Methods: Sixty incisor teeth (20 higid and 40 with root fracture) from dogs were
inserted in 60 anterior alveolar sockets (40 higid and 20 with alveolar fracture)
of 15 macerated canine maxillae. Each fractured socket had a root fractured tooth
inserted in it. Afterwards, each maxilla was submitted to PR in two different
vertical angulation incidences, and to CBCT imaging with a small field of view
(FOV) and high-definition protocol. Images were randomized and posteriorly
analyzed by two oral and maxillofacial radiologists two times, with a two-week
interval between observations. Results: Sensitivity and specificity values were
good for root fractures for PR and CBCT. For alveolar fractures, sensitivity
ranged from 0.10 to 0.90 for PR and from 0.50 to 0.65 for CBCT. Specificity for
alveolar fractures showed lower results than for root fractures for PR and CBCT.
Areas under the ROC curve showed good results for both PR and CBCT for root
fractures. However, results were fair for both PR and CBCT for alveolar
fractures. When submitted to repeated measures ANOVA tests, there was a
statistically significant difference between PR and CBCT for root fractures. Root
fracture intraobserver agreement ranged from 0.90 to 0.93, and alveolar fracture
intraobserver agreement ranged from 0.30 to 0.57. Interobserver agreement results
were substantial for root fractures and poor/fair for alveolar fractures (0.11
for PR and 0.30 for CBCT). Conclusion: Periapical radiograph with two different
vertical angulations may be considered an accurate method to detect root
fractures. However, PR showed poorer results than CBCT for the diagnosis of
alveolar fractures. When no fractures are diagnosed in PR and the patient
describes pain symptoms, the subsequent exam of choice is CBCT.
PMID- 28403366
TI - Nurses' knowledge and practices regarding pain management in newborns.
AB - OBJECTIVE: To analyze nurses' knowledge and practices regarding pain management
of newborns admitted to Neonatal Intensive Care Units. METHOD: A descriptive and
cross-sectional study. Data were collected from 51 nurses based on an adapted
questionnaire aimed at evaluating knowledge and practices regarding the
management of neonatal pain in six hospitals in Curitiba and its Metropolitan
Region. RESULTS: For most nurses (86.0%), neonates feel pain. A total of 34.7% of
the nurses reported never using pain assessment scales. Pain management was
recorded by 84.3% of the nurses. Administered pharmacological measures were
Paracetamol and Fentanyl (47.1%) and Morphine (17.6%); while non-pharmacological
measures adopted were sweetened solution (68.6%), non-nutritive sucking (58.8%)
and positioning (56.9%). CONCLUSION: Nurses considered neonatal pain a real
event; however, they do not perform pain assessment or treatment of newborns in a
systematized way.It is necessary to implement knowledge translation strategiesin
order to improve pain management in newborns. OBJETIVO: Verificar o conhecimento
e as praticasdos enfermeiros sobreo manejo da dor de recem-nascidos admitidos em
Unidades de Tratamento Intensivo Neonatal. METODO: Estudo descritivo e
transversal. Os dados foram coletados com 51 enfermeiros, a partir de um
questionario adaptado que visa avaliar o conhecimento e as praticas sobre o
manejo da dor neonatal, em seis hospitais de Curitiba e Regiao Metropolitana.
RESULTADOS: Para a maioria dos enfermeiros(86,0%), os neonatos sentem dor. Um
total de 34,7% afirmaramnunca utilizar escalas de avaliacaoda dor. O registro do
manejo da dor foi realizado por 84,3% dos enfermeiros. As medidas farmacologicas
realizadas foram Paracetamol e Fentanil (47,1%) e Morfina (17,6%);as nao
farmacologicas adotadas foram solucao adocicada (68,6%), succao nao nutritiva
(58,8%) e posicionamento (56,9%). CONCLUSAO: Os enfermeiros consideraram a dor
neonatal como um evento real, porem nao realizavam avaliacao ou tratamento da dor
no recem-nascido de modosistematizado. E necessario implementarestrategias de
traducao do conhecimento paraaprimorar o manejo da dor de recem-nascidos.
PMID- 28403365
TI - Crown discoloration promoted by materials used in regenerative endodontic
procedures and effect of dental bleaching: spectrophotometric analysis.
AB - Objectives: To assess tooth crown's color after intracanal treatment with triple
antibiotic paste (TAP) or calcium hydroxide (CH); cervical sealing with glass
ionomer cement (GIC) or mineral trioxide aggregate (MTA); and bleaching with
carbamide peroxide. Material and Methods: After pulp removal and color
spectrophotometer measurement, 50 bovine incisors were divided into 4
experimental groups and one control (untreated). Experiments were performed in
phases (Ph). Ph1: TAP (ciprofloxacin, metronidazole, minocycline), TAPM
(ciprofloxacin, metronidazole, amoxicillin), DAP (ciprofloxacin, metronidazole),
or CH treatment groups. After 1 and 3 days (d); 1, 2, 3 weeks (w); and 1, 2, 3
and 4 months (m), color was measured and medications were removed. Ph2: GIC or
MTA cervical sealing, each using half of the specimens from each group. Color was
assessed after 1d, 3d; 1w, 2w, 3w; 1m and 2m. Ph3: Two bleaching sessions, each
followed by color measurement. Data were analyzed with ANOVA and post-hoc Holm
Sidak method. Results: Ph1: Specimens of TAP group presented higher color
alteration (DeltaE) mean than those of TAPM group. No significant difference was
found among TAP or TAPM and CH, DAP or Control groups. Ph2: cervical sealing
materials showed no influence on color alteration. Ph3: Different DeltaE means
(from different groups), prior to bleaching, became equivalent after one
bleaching session. Conclusions: TAP induces higher color alteration than TAPM;
color alteration increases over time; cervical sealing material has no influence
on color alteration; and, dental bleaching was able to recover, at least
partially, the tooth crown's color.
PMID- 28403367
TI - Discourses of healthcare professionals about health surveillance actions for
Tuberculosis control.
AB - OBJECTIVE: To analyze the meanings produced in the Health Surveillance actions
for tuberculosis control, carried out by healthcare professionals in Mozambique.
METHOD: Qualitative study using the theoretical and methodological framework of
the French Discourse Analysis. RESULTS: A total of 15 healthcare professionals
with more than one year of experience in disease control actions participated in
the study. Four discursive blocks have emerged from the analysis: tuberculosis
diagnosis process; meeting, communication and discussion of treatment; local
strategies for tuberculosis control; involvement of family and community leaders
in the tuberculosis control. CONCLUSION: The statements of the healthcare
professionals suggest, as Health Surveillance actions, practices that include
collecting sputum in the patient's home and sending it to the laboratory;
deployment of the medical team with a microscope for tuberculosis testing; and
testing for diseases that may be associated with tuberculosis. In this context,
the actions of Health Surveillance for tuberculosis control involve valuing all
actors: family, community leaders, patients and health professionals. OBJETIVO:
Analisar os sentidos produzidos sobre as acoes de Vigilancia em Saude no controle
da tuberculose desenvolvidas por profissionais de saude em Mocambique. METODO:
Estudo qualitativo que tem como referencial teorico-metodologico a Analise de
Discurso de matriz francesa. RESULTADOS: Participaram do estudo 15 profissionais
de saude, com mais de 1 ano de experiencia em acoes de controle da doenca. Da
analise, emergiram quatro blocos discursivos: processo do diagnostico da
tuberculose; reuniao, comunicacao e discussao do tratamento; estrategias locais
para o controle da tuberculose; envolvimento da familia e dos lideres
comunitarios no controle da tuberculose. CONCLUSAO: Os dizeres dos profissionais
de saude sugerem, como acoes de Vigilancia em Saude, praticas que incluem a
coleta de escarro na residencia do paciente e seu encaminhamento ao laboratorio;
o deslocamento da equipe medica com microscopio para a testagem da tuberculose; e
a testagem das doencas que podem estar associadas a tuberculose. Nesse contexto,
as acoes de Vigilancia em Saude no controle da tuberculose envolvem a valorizacao
de todos os atores: familia, lideres comunitarios, pacientes e profissionais de
saude.
PMID- 28403368
TI - Women's pelvic floor muscle strength and urinary and anal incontinence after
childbirth: a cross-sectional study.
AB - OBJECTIVE: To analyse pelvic floor muscle strength (PFMS) and urinary and anal
incontinence (UI and AI) in the postpartum period. METHOD: Cross-sectional study
carried out with women in their first seven months after child birth. Data were
collected through interviews, perineometry (PeritronTM), and the International
Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS: 128
women participated in the study. The PFMS mean was 33.1 (SD=16.0) cmH2O and the
prevalence of UI and AI was 7.8% and 5.5%, respectively. In the multiple
analyses, the variables associated with PFMS were type of birth and cohabitation
with a partner. Newborn's weight, previous pregnancy, UI during pregnancy, and
sexual activity showed an association with UI after child birth. Only AI prior to
pregnancy was associated with AI after childbirth. CONCLUSION: Vaginal birth
predisposes to the reduction of PFMS, and caesarean section had a protective
effect to its reduction. The occurrence of UI during pregnancy is a predictor of
UI after childbirth, and women with previous pregnancies and newborns with higher
weights are more likely to have UI after childbirth.AI prior to pregnancy is the
only risk factor for its occurrence after childbirth. Associations between PFMS
and cohabitation with a partner, and between UI and sexual activity do not make
possible to conclude that these variables are directly associated. OBJETIVO:
Analisar a forca dos musculos do assoalho pelvico e a incontinencia urinaria e
anal no periodo pos-parto. METODO: Estudo transversal realizado com mulheres nos
primeiros 7 meses apos o parto. Os dados foram coletados por meio de entrevista,
da perineometria (PeritronTM) e do International Consultation on Incontinence
Questionnaire-Short Form (ICIQ-SF). RESULTADOS: Participaram do estudo 128
mulheres. A media da forca dos musculos do assoalho pelvico foi 33,1 (d.p.=16,0)
cmH2O e a prevalencia de incontinencia urinaria e incontinencia anal foi de 7,8%
e 5,5%, respectivamente. Na analise multipla, as variaveis associadas a forca dos
musculos do assoalho pelvico foram tipo de parto atual e coabitacao com o
parceiro. Peso do recem-nascido, gestacao anterior, incontinencia urinaria na
gestacao e atividade sexual mostraram associacao. Apenas a incontinencia anal
previa a gestacao associou-se a incontinencia anal apos o parto. CONCLUSAO: O
parto vaginal predispoe a reducao da forca dos musculos do assoalho pelvico, e a
cesariana exerce funcao protetora a sua reducao. A ocorrencia de incontinencia
urinaria na gestacao e preditora da incontinencia urinaria apos o parto, e as
mulheres com gestacao anterior e recem-nascido de maior peso tem maior propensao
em apresentar incontinencia urinaria apos o parto. Incontinencia anal previa a
gestacao e o unico fator de risco para sua ocorrencia apos o parto. As
associacoes entre forca dos musculos do assoalho pelvico e coabitacao com o
parceiro e entre incontinencia urinaria e atividade sexual nao permitem concluir
que essas variaveis estejam diretamente relacionadas.
PMID- 28403370
TI - Adherence and factors related to acceptance of alcohol for antiseptic hand
rubbing among nursing professionals.
AB - OBJECTIVE: Identify rates of adhesion and related factors to acceptance of an
alcohol based preparation to hands antiseptic friction among nursing
professionals in a unit of intensive therapy. METHOD: A cross-sectional study,
which involved direct observation of hand hygiene opportunities and nursing
professionals' completion of questionnaires, was conducted at a university
hospital between January and July 2015. Descriptive and univariate analyses were
performed, with a 5% significance level. RESULTS: It was observed 956
opportunities of hand hygiene among 46 nursing professionals. The rate of
adhesion to alcohol-based handrub (ABH) was 34.8% and about 87.0% preferred
handwashing. Nurses used ABH more frequently than nursing technicians (p <0.001),
and the report of feeling of clean hands after using the alcohol product was
directly related to higher rates of adherence to antiseptic friction through
observation (P <0.05). CONCLUSION: The finding indicating low ABH usage
highlights the need for greater institutional investment in strategies that help
health professionals to recognize the advantages of this type of HH with respect
to time spent, ease of access to dispensers, effectiveness in eliminating
microorganisms, and maintaining skin moisturization.
PMID- 28403369
TI - Fear of falling in older adults living at home: associated factors.
AB - OBJECTIVE: To identify the factors associated with the fear of falling in the
older adultliving at home. METHOD: Cross-sectional study with probabilistic
sampling of older adultenrolled in two Family Health Strategies (FHS). The fear
of falling was measured by the Brazilian version of the Falls Efficacy Scale
International and by a household questionnairethat contained the explanatory
variables. Multiple Linear Regression using the stepwise selection technique and
the Generalized Linear Models were used in the statistical analyses. RESULTS: A
total of170 older adultsparticipated in the research, 85 from each FHS. The
majority (57.1%) aged between 60 and 69; 67.6% were female; 46.1% fell once in
the last year. The majority of the older adults(66.5%) had highfear of falling.
In the final multiple linear regression model, it was identified that a higher
number of previous falls, female gender, older age, and worse health self
assessment explained 37% of the fear of falling among the older adult.
CONCLUSION: The findings reinforce the need to assess the fear of falling among
the older adultliving at home, in conjunction with the development and use
ofstrategies based on modifiable factors by professionalsto reduce falls and
improve health status, which may contribute to the reduction of the fear of
falling among the older adult. OBJETIVO: Identificar os fatores associados ao
medo de cair em idosos residentes no domicilio. METODOS: Estudo transversal com
amostragem probabilistica de idosos cadastrados em duas Estrategias Saude da
Familia (ESF). O medo de cair foi avaliado pela versao brasileira da escala Falls
Efficacy Scale International e por um inquerito domiciliar que continha as
variaveis explicativas.A Regressao Linear Multipla por meio da tecnica stepwise
selectione osModelos Lineares Generalizados foram utilizados nas analises
estatisticas. RESULTADOS: Participaram da pesquisa170 idosos, 85 de cada ESF. A
maioria (57,1%) tinha entre 60 e 69 anos de idade; 67,6% eram do sexo feminino;
46,1% tiveram queda no ultimo ano. A maioria dos idosos (66,5%) tinha elevado
medo de cair. No modelo final de regressao multivariada, identificou-se que maior
numero de quedas anteriores, sexo feminino, idade mais avancada, e pior
autoavaliacao de saude explicaram 37% do medo de cair entre os idosos. CONCLUSAO:
Os achados reforcam a necessidade da avaliacao do medo de cair entre os idosos
que residem no proprio domicilio, assim como o desenvolvimento e a utilizacao de
estrategias pelos profissionais voltadas para os fatores modificaveis,de modo a
reduzir as quedas e melhorar o estado de saude, o que pode contribuir para a
diminuicao do medo de cair entre os idosos.
PMID- 28403371
TI - Development of a theoretical-practical script for clinical simulation.
AB - OBJECTIVE: To develop a theoretical-practical script based on the opinion of
experts to be used in simulated clinical activities. METHOD: Qualitative study
through analysis of content of interviews with experts on the theme in order to
develop the proposed script. Of the 24 invited experts, 12 specialists from
educational institutions in Brazil and abroad participated in the study in
compliance with the ethical precepts. The experts responded to questions on the
characterization of their study attributes and described the items required for
the development of a simulated scenario. In view of the responses obtained, data
content was analyzed and classified into units and subunits of significance.
RESULTS: The items mentioned for the development of the script generated seven
units of significance. The units and subunits of significance were gathered in
three stages of the main components of the simulated scenario: prior,
preparation, and finals. CONCLUSION: This study enables an innovative,
stimulating teaching experience, making it easier for professors to use the
simulation resource as a learning process in an effective and objective manner,
as a guide to professors and researchers in the area of clinical simulation.
OBJETIVO: Construir, com base na opiniao de peritos, roteiro teorico-pratico para
uso em atividade clinica simulada. METODO: Trata-se de um estudo qualitativo por
meio de analise de conteudo de entrevistas de peritos no assunto para construcao
do roteiro proposto. Seguido os preceitos eticos, entre os 24 peritos convidados
pertencentes a instituicoes de ensino do Brasil e do exterior. Os peritos
responderam a questoes sobre a caracterizacao dos seus atributos de estudo e
descreveram os itens imprescindiveis a construcao de um cenario simulado. Diante
das respostas obtidas, os dados foram analisados em relacao ao seu conteudo e
organizados em unidades e subunidades de significancia. RESULTADOS: Participaram
12 especialistas. Os itens mencionados para construcao do roteiro originaram sete
unidades de significancia. As unidades e suas subunidades de significancia foram
ainda reunidas em tres fases dos componentes principais do cenario simulado:
previos, preparo e finais. CONCLUSAO: Este estudo permite um ensino inovador,
estimulante e possibilita a facilidade ao professor, quanto a utilizacao do
recurso de simulacao, como processo de aprendizagem de maneira eficiente e
objetiva, sendo um norteador aos docentes e pesquisadores na area de simulacao
clinica.
PMID- 28403372
TI - Editorial.
PMID- 28403373
TI - Different inoculum loads of Toxoplasma gondii induce reduction of myenteric
neurons of the rat colon.
AB - Toxoplasmosis, a disease caused by Toxoplasma gondii, is an important health
problem, especially in immunocompromised hosts. T. gondii uses the gut wall as an
infection gateway, with tropism for muscular and nervous tissues causing
intestinal alterations, including some in the enteric nervous system. This study
aims at investigating the colon of rats infected by T. gondii in order to
understand how the amount of oocysts influences in myenteric neuronal changes.
Sixty Wistar rats (Rattus norvegicus) were divided into six groups. One group
remained as a control and the others received inocula of 10, 50, 100, 500 or
5,000 oocysts of T. gondii. The animals were euthanized after 30 days of
infection. The total neuronal population and the nitrergic subpopulation in the
colon myenteric plexus of each animal was counted. The data were statistically
analyzed showing less weight gain in rats with 10, 500 and 5,000 oocysts. A
decrease in the number of total neurons with 50, 100 or 5,000 oocysts and an
increase in the nitrergic population with 10, 100, 500 or 5,000 oocysts were
verified. These results show that neuronal alterations are more significant when
the infection is induced by larger inocula and reinforces the suspicion that
neuronal loss is directed at cholinergic neurons.
PMID- 28403374
TI - rROP2 from Toxoplasma gondii as a potential vaccine against oocyst shedding in
domestic cats.
AB - The aim of the present study was to evaluate oocyst shedding in cats immunized by
nasal route with T. gondii proteins ROP2. Twelve short hair cats (Felis catus)
were divided in three groups G1, G2 and G3 (n=4). Animals from G1 received 100
MUg of rROP2 proteins plus 20 MUg of Quil-A, G2 received 100 MUg of BSA plus 20
MUg of Quil-A, and the G3 only saline solution (control group). All treatments
were done by intranasal route at days 0, 21, 42, and 63. The challenge was
performed in all groups on day 70 with ? 800 tissue cysts of ME-49 strain by oral
route. Animals from G1 shed less oocysts (86.7%) than control groups. ELISA was
used to detect anti-rROP2 IgG and IgA, however, there were no correlation between
number of oocyst shedding by either IgG or IgA antibody levels. In the present
work, in spite of lesser oocysts production in immunized group than control
groups, it was not possible to associate the use of rROP2 via nostrils with
protection against oocyst shedding. For the future, the use of either other
recombinant proteins or DNA vaccine, in combination with rROP2 could be tested to
try improving the efficacy of this kind of vaccine.
PMID- 28403375
TI - Helminth fauna of Leptodactylus syphax (Anura: Leptodactylidae) from Caatinga
biome, northeastern Brazil.
AB - Leptodactylus syphax is distributed in central, southeastern and northeastern
Brazil, eastern Bolivia and southern Paraguay, occupying open areas and rock
outcrops, in rock cavities and termite burrows. We collected 21 frogs from the
Caatinga region of the state of Ceara, northeastern Brazil, and 7,021 helminths
were recovered from 18 of these hosts (overall prevalence = 85.7%). Six helminth
taxa were recovered, as follows: Aplectana membranosa (n = 3,756); Schrankiana
formosula (n = 3,176); larvae of Physaloptera sp. (n = 43); unidentified nematode
larvae (n = 7); digenean metacercariae of Lophosicyadiplostomum sp. (n = 2); and
cystacanths of Acanthocephala (n = 37). The similarity of helminth composition
between L. syphax from the Caatinga and other species of the L. fuscus group
showed that some anurans were clustered according to parasite species and others
according to geographic locality. This study presents new helminth records for
the Neotropical region, thus helping in understanding the pattern of species
distribution, and it increases the knowledge of parasites associated with
amphibians.
PMID- 28403376
TI - Eruption of Yellow-Brown and Red-Brown Papules in a Young Adult With Polydipsia
and Polyuria.
PMID- 28403377
TI - Use of Targeted Therapy in the Treatment of Advanced Cutaneous Cancers.
PMID- 28403378
TI - Inaccurate Claims About VA Surgical Quality Might Mislead Veterans.
PMID- 28403380
TI - Developing the health informatics workforce of the future: academic and industry
partners.
PMID- 28403379
TI - Effect of Resveratrol on Walking Performance in Older People With Peripheral
Artery Disease: The RESTORE Randomized Clinical Trial.
AB - Importance: Research shows that resveratrol, a sirtuin activator in red wine,
improves exercise endurance and skeletal-muscle oxidative metabolism in animals
and may enhance vascular function in humans. Resveratrol supplement sales exceed
$30 million annually in the United States, but few data are available regarding
its efficacy in humans. Objective: To determine whether resveratrol, 125 mg/d or
500 mg/d, improves the 6-minute walk performance in patients with peripheral
artery disease (PAD). Design, Setting, and Participants: This parallel-design,
double-blind, randomized clinical trial, called Resveratrol to Improve Outcomes
in Older People With PAD (RESTORE), was conducted at Northwestern University.
Sixty-six participants 65 years or older with PAD were randomized to receive a
daily capsule of resveratrol, 125 mg or 500 mg, or placebo for 6 months.
Participants were randomized using a randomly permuted block method stratified by
baseline 6-minute walk test performance. This trial was conducted between January
1, 2015, and August 5, 2016, and data analyses were performed according to the
intention-to-treat concept. Interventions: Administration of resveratrol, 125 or
500 mg/d, or placebo once daily. Main Outcomes and Measures: The primary outcome
measure was the change in 6-minute walk distance at the 6-month follow-up. One of
the secondary outcomes was change in maximal treadmill walking time. Because of
the preliminary nature of the trial, the a priori power calculation used a 1
sided test with a significance level of P < .10. Results: The 66 participants
were predominantly men (45 [68%]), had a mean (SD) age of 74.4 (6.6) years, and
had a mean (SD) ankle brachial index of 0.67 (0.18). Sixty-four (97%) completed
follow-up. Six-month mean (SE) changes in 6-minute walk distance were 4.6 (8.1) m
for the 125-mg resveratrol group, -12.8 (7.5) m for the 500-mg resveratrol group,
and -12.3 (7.9) m for the placebo group (P = .07 for the 125-mg resveratrol group
vs placebo; P = .96 for the 500-mg resveratrol group vs placebo). Six-month mean
(SE) changes in maximal treadmill walking time were 0.5 (2.3) minutes for the 125
mg resveratrol group, -0.6 (2.1) minutes for the 500-mg resveratrol group, and
0.4 (2.1) minutes for the placebo group (P = .18 for the 125-mg resveratrol group
vs placebo; P = .12 for the 500-mg resveratrol group vs placebo). Conclusions and
Relevance: The RESTORE trial found no consistent evidence that resveratrol
improves walking performance in patients 65 years or older with PAD. Trial
Registration: clinicaltrials.gov Identifier: NCT02246660.
PMID- 28403381
TI - Advancing healthcare and biomedical research via new data-driven approaches.
PMID- 28403382
TI - Molecular Profiling of Multiple Primary Merkel Cell Carcinoma to Distinguish
Genetically Distinct Tumors From Clonally Related Metastases.
AB - Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine
carcinoma. In rare cases, the development of an additional cutaneous MCC tumor is
clinically consistent with a second primary MCC tumor rather than a cutaneous
metastasis, which has important treatment and prognostic implications. Objective:
To evaluate genetic relatedness in 4 cases with the clinical diagnosis of
multiple primary MCCs. Design, Setting, and Participants: In this case series, 7
cases of clinically designated multiple primary MCC were identified; 4 cases met
inclusion criteria for next-generation sequencing (NGS) analysis. Mutations, copy
number alterations, and Merkel cell polyomavirus (MCPyV) sequence were analyzed
and compared between clinically designated multiple primary tumors to
characterize genetic relatedness and hence assess clonality. Patients with
clinically designated multiple primary MCC were identified from the
multidisciplinary MCC Program at the University of Michigan, a tertiary care
center. Main Outcomes and Measures: Four cases of clinically designated multiple
primary MCC were characterized by tumor sequencing and targeted MCPyV sequencing
to distinguish independent primary tumors from related metastases. Results:
Overall, 4 patients in their 70s or 80s were included and analyzed. Cases 1 and 4
were verified as genetically distinct primary tumors and did not harbor similar
copy number alterations or demonstrate significant mutational overlap. Cases 2
and 3 were designated as clonally related based on overlapping copy number
alterations. In clonally related tumors, chromosomal copy number changes were
more reliable than mutations for demonstrating clonality. Regardless of
clonality, we found that MCPyV status was concordant for all tumor pairs and
MCPyV positive tumors harbored predominatly subclonal mutations. Conclusions and
Relevance: Our findings suggest that patients with MCC may develop a second
genetically distinct primary tumor; in this case, the subsequent tumor is likely
to develop through similar mechanisms of pathogenesis, either MCPyV-mediated or
ultraviolet light-mediated. Next-generation sequencing analysis of chromosomal
copy number changes and mutations is useful in distinguishing multiple primary
MCCs from progression of MCC clinically resembling multiple primaries, allowing
appropriate staging of the patient.
PMID- 28403384
TI - Sex Hormones and Hair Loss in Men From the General Population of Northeastern
Germany.
PMID- 28403385
TI - Targeting Surgical Site Infection-Reducing Bundles Selectively to At-Risk Colon
Cancer Surgery Populations: Achieving Value in a MACRA World?
PMID- 28403386
TI - Correction of Axis Labels in 3 Figures.
PMID- 28403383
TI - Neural Signatures of Cognitive Flexibility and Reward Sensitivity Following
Nicotinic Receptor Stimulation in Dependent Smokers: A Randomized Trial.
AB - Importance: Withdrawal from nicotine is an important contributor to smoking
relapse. Understanding how reward-based decision making is affected by abstinence
and by pharmacotherapies such as nicotine replacement therapy and varenicline
tartrate may aid cessation treatment. Objective: To independently assess the
effects of nicotine dependence and stimulation of the nicotinic acetylcholine
receptor on the ability to interpret valence information (reward sensitivity) and
subsequently alter behavior as reward contingencies change (cognitive
flexibility) in a probabilistic reversal learning task. Design, Setting, and
Participants: Nicotine-dependent smokers and nonsmokers completed a probabilistic
reversal learning task during acquisition of functional magnetic resonance
imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design
conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent
from cigarette smoking for 12 hours for all sessions. In a fully Latin square
fashion, participants in both groups underwent MRI twice while receiving
varenicline and twice while receiving a placebo pill, wearing either a nicotine
or a placebo patch. Imaging analysis was performed from June 15, 2015, to August
10, 2016. Main Outcome and Measures: A well-established computational model
captured effects of smoking status and administration of nicotine and varenicline
on probabilistic reversal learning choice behavior. Neural effects of smoking
status, nicotine, and varenicline were tested for on MRI contrasts that captured
reward sensitivity and cognitive flexibility. Results: The study included 24
nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years)
and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years).
Computational modeling indicated that abstinent smokers were biased toward
response shifting and that their decisions were less sensitive to the available
evidence, suggesting increased impulsivity during withdrawal. These behavioral
impairments were mitigated with nicotine and varenicline. Similarly, decreased
mesocorticolimbic activity associated with cognitive flexibility in abstinent
smokers was restored to the level of nonsmokers following stimulation of
nicotinic acetylcholine receptors (familywise error-corrected P < .05).
Conversely, neural signatures of decreased reward sensitivity in smokers (vs
nonsmokers; familywise error-corrected P < .05) in the dorsal striatum and
anterior cingulate cortex were not mitigated by nicotine or varenicline.
Conclusions and Relevance: There was a double dissociation between the effects of
chronic nicotine dependence on neural representations of reward sensitivity and
acute effects of stimulation of nicotinic acetylcholine receptors on behavioral
and neural signatures of cognitive flexibility in smokers. These chronic and
acute pharmacologic effects were observed in overlapping mesocorticolimbic
regions, suggesting that available pharmacotherapies may alleviate deficits in
the same circuitry for certain mental computations but not for others. Trial
Registration: clinicaltrials.gov Identifier: NCT00830739.
PMID- 28403388
TI - Negative Psychosis Prevention Trials.
PMID- 28403389
TI - Safety for the Surgical Patient-What Will "Move the Needle?": The 2016 National
Surgical Patient Safety Summit.
PMID- 28403387
TI - Skin Conductance Responses and Neural Activations During Fear Conditioning and
Extinction Recall Across Anxiety Disorders.
AB - Importance: The fear conditioning and extinction neurocircuitry has been
extensively studied in healthy and clinical populations, with a particular focus
on posttraumatic stress disorder. Despite significant overlap of symptoms between
posttraumatic stress disorder and anxiety disorders, the latter has received less
attention. Given that dysregulated fear levels characterize anxiety disorders,
examining the neural correlates of fear and extinction learning may shed light on
the pathogenesis of underlying anxiety disorders. Objectives: To investigate the
psychophysiological and neural correlates of fear conditioning and extinction
recall in anxiety disorders and to document how these features differ as a
function of multiple diagnoses or anxiety severity. Design, Setting, and
Participants: This investigation was a cross-sectional, case-control, functional
magnetic resonance imaging study at an academic medical center. Participants were
healthy controls and individuals with at least 1 of the following anxiety
disorders: generalized anxiety disorder, social anxiety disorder, specific
phobia, and panic disorder. The study dates were between March 2013 and May 2015.
Exposures: Two-day fear conditioning and extinction paradigm. Main Outcomes and
Measures: Skin conductance responses, blood oxygenation level-dependent
responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait
Form, and functional connectivity. Results: This study included 21 healthy
controls (10 women) and 61 individuals with anxiety disorders (36 women). P
values reported for the neuroimaging results are all familywise error corrected.
Skin conductance responses during extinction recall did not differ between
individuals with anxiety disorders and healthy controls (etap2 = 0.001, P = .79),
where etap2 is partial eta squared. The anxiety group had lower activation of the
ventromedial prefrontal cortex (vmPFC) during extinction recall (etap2 = 0.178, P
= .02). A similar hypoactive pattern was found during early conditioning (etap2 =
0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom
severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for
extinction recall) and the number of co-occuring anxiety disorders diagnosed
(etap2 = 0.137, P = .009 for conditioning and etap2 = 0.227, P = .004 for
extinction recall). Psychophysiological interaction analyses revealed that the
fear network connectivity differed between healthy controls and the anxiety group
during fear learning (etap2 range between 0.088 and 0.176 and P range between
0.02 and 0.003) and extinction recall (etap2 range between 0.111 and 0.235 and P
range between 0.02 and 0.002). Conclusions and Relevance: Despite no skin
conductance response group differences during extinction recall, brain activation
patterns between anxious and healthy individuals differed. These findings
encourage future studies to examine the conditions longitudinally and in the
context of treatment trials to improve and guide therapeutics via advanced
neurobiological understanding of each disorder.
PMID- 28403390
TI - Outcomes Associated With Subcutaneous Implantable Cardioverter Defibrillators.
PMID- 28403391
TI - Outcomes Associated With Subcutaneous Implantable Cardioverter Defibrillators
Reply.
PMID- 28403392
TI - Association of Central Nervous System Depression With Topical Brimonidine When
Used for Hemostasis: A Serious Adverse Event.
AB - Importance: Minor bleeding is the most common complication of dermatologic
surgery. Topical brimonidine, 0.33%, gel has been reported for the use of
hemostasis in dermatologic surgery. The safety profile and risk of systemic toxic
effects when brimonidine is used topically for hemostasis is unknown. Objective:
To determine the risk of systemic toxic effects of topical brimonidine, 0.33%,
gel when used for hemostasis. Design, Setting, and Participants: In this case
series from a private practice (Hollywood Dermatology), 2 patients presented for
dermatologic procedures, complicated by persistent bleeding. Interventions:
Patients were treated with 10 g of brimonidine, 0.33%, gel applied under
occlusion for hemostasis. Main Outcomes and Measures: Mental status,
cardiopulmonary function. Results: Both patients experienced deterioration of
mental status, respiratory depression, and somnolence. Results from cardiac
testing, laboratory workup, and imaging were negative for cardiac or neurologic
etiology. Both patients improved in less than 24 hours. Conclusions and
Relevance: Topical brimonidine, 0.33%, gel can result in systemic central nervous
system toxic effects when used as a hemostatic agent. At present, it is not
possible to define a quantity with which brimonidine can be used safely, nor can
a safe wound size be defined. We, therefore, urge against the use of topical
brimonidine as a hemostatic agent until its safety is further investigated.
PMID- 28403393
TI - Estimated Cost of Emergency Sunburn Visits-Reply.
PMID- 28403394
TI - National audits in the UK: fancy acronyms or real patient benefit?
PMID- 28403396
TI - Theory and context: putting the science into improvement.
PMID- 28403395
TI - Individual patient data analysis of tidal volumes used in three large randomized
control trials involving patients with acute respiratory distress syndrome.
AB - Background.: The acute respiratory distress syndrome (ARDS) is a condition with a
high mortality and morbidity. Mechanical ventilation prevents immediate mortality
but may further damage patients' lungs. Low tidal volume lung-protective
strategies have been shown to increase survival by reducing this iatrogenic
damage. Current guidelines recommend tidal volumes of 6-8 ml kg -1 of predicted
body weight. We used data from three large randomized controlled trials of
treatments for ARDS to determine compliance with these recommendations. Methods.:
We used the tidal volume recorded at randomization for all patients in the OSCAR,
HARP-2, and BALTI-2 studies. In addition, we used the ventilation data for
control arm patients in OSCAR and all patients in HARP-2 at days 1 and 7 after
randomization. Results.: The three trials enrolled 1660 patients, with tidal
volume data available at least at one time point in 1412 patients. Compliance
with the 6-8 ml kg -1 recommendation for tidal volume ranged from 20 to 39% of
patients across all time points in all three trials. Conclusion.: Poor compliance
with the guidelines for tidal volume in patients with ARDS has been demonstrated
before in case series, but not in clinical trials where the patient population is
specifically selected against standard ARDS diagnostic criteria and the
investigators were encouraged to use low tidal volumes. This study may indicate a
need to improve implementation and compliance with protective lung ventilation.
PMID- 28403397
TI - Complications of robotic-assisted laparoscopic surgery distant from the surgical
site.
AB - With the ever-increasing popularity of robotic-assisted laparoscopic surgery over
the past decades, the literature reporting complications distant from the
surgical site involving the use of this technology has also grown. The goal of
this non-systematic review is to summarise these reports with a systems-based
presentation of these complications. The most commonly observed complications
were related to the peripheral nervous system and the most devastating occurring
in cardiac and ophthalmic systems. There were no reports of patient complications
directly related to the robot itself. While several of the reported complications
are not unique to robotic surgery, they are included to maintain awareness of
their possibility. The limitation of surgical time, judicious fluid
administration, and constant vigilance of patient positioning are all recommended
as possible preventative measures.
PMID- 28403398
TI - Systematic review of the systemic concentrations of local anaesthetic after
transversus abdominis plane block and rectus sheath block.
AB - Background.: Safe and efficacious modalities of perioperative analgesia are
essential for enhanced recovery after surgery. Truncal nerve blocks are one
potential adjunct for analgesia of the abdominal wall, and in recent years their
popularity has increased. Transversus abdominis plane block (TAPB) and rectus
sheath block (RSB) have been shown to reduce morphine consumption and improve
pain relief after abdominal surgery. These blocks typically require large volumes
of local anaesthetic (LA). We aimed to synthesize studies evaluating systemic
concentrations of LA after perioperative TAP and RSB to enhance our understanding
of systemic LA absorption and the risk of systemic toxicity. Methods.: An
independent literature review was performed in accordance with the methods
outlined in the Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA) statement. An electronic search of four databases (MEDLINE,
EMBASE, Cochrane Central Register of Controlled Trials, and PubMed) was
conducted. Primary articles measuring systemic concentrations of LA after single
shot bolus TAPB or RSB were included. Results.: Fifteen studies met the inclusion
criteria. Rapid systemic LA absorption was observed in all studies. Of a total of
381 patients, mean peak concentrations of LA exceeded toxic thresholds in 33
patients, of whom three reported mild adverse effects. The addition of
epinephrine reduced systemic absorption of LA. No instances of seizure or cardiac
instability were observed. Conclusions.: Local anaesthetic in TAPB and RSB can
lead to detectable systemic concentrations that exceed commonly accepted
thresholds of LA systemic toxicity. Our study highlights that these techniques
are relatively safe with regard to LA systemic toxicity.
PMID- 28403399
TI - The role of microglia in the pathobiology of neuropathic pain development: what
do we know?
AB - Neuropathic pain, a maladaptive and chronic condition that can develop after a
lesion or disease affecting the somatosensory system, is characterized by
allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep
deprivation, depression and anxiety. The activation of microglial cells in
response to nerve injury has been implicated in the development of neuropathic
pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9,
The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after
nerve injury and are involved in the activation of microglial cells. These
activated cells in turn release factors that increase the excitation and decrease
the inhibition of interneurons. Microglial cells release factors such as
interleukin (IL)-6, IL-1beta and tumour necrosis factor-alpha (TNF-alpha) that
cause the painful symptoms. It is becoming increasingly apparent that an
intricate network of cytokines and cellular signalling mechanisms underpin the
complex relationship between microglia and various cell types including neurones,
astrocytes, oligodendrocytes, mast cells and T-cells. Although the precise
mechanism of action of microglial cells in producing neuropathic pain has not
been completely elucidated, research into these different activating factors and
cytokines is providing further insight into the role of microglial cells in the
development and maintenance of neuropathic pain. Further studies also are
required to elucidate how "pain" mediators act on neurones and how the
interactions between these mediators, or between neurones and glia in the
presence of these mediators occur, in order to develop effective therapies for
the management of neuropathic pain.
PMID- 28403400
TI - Association of intraoperative cerebral and muscular tissue oxygen saturation with
postoperative complications and length of hospital stay after major spine
surgery: an observational study.
AB - Background.: Compromised tissue oxygenation is one of the root causes of
dysfunction of various organs and postoperative complications. Oxygenation of
different tissue beds may follow different patterns of change during
physiological derangement. Methods.: Patients undergoing elective major posterior
spine surgery participated in this prospective observational study. Cerebral
tissue oxygen saturation (SctO 2 ) was monitored on the upper forehead and
muscular tissue oxygen saturation (SmtO 2 ) on the lower leg. The associations of
various oxygenation indices with postoperative composite complications and length
of hospital stay (LOH) were investigated. Results.: The number of composite
complications per patient was 3 (2) while the LOH was 6 (3) days (n = 102).
Multiple SmtO 2 indices (maximum, minimum, mean, median, and area under curve
(AUC)) were associated with composite complications (univariate analysis, P <
0.05). No SctO 2 indices were associated with complications. Multiple SmtO 2
indices (maximum, mean, median, and AUC) showed differences ( P < 0.05) between
patients with composite complications <=3 and >3, respectively. SmtO 2 standard
deviation, AUC, and AUC weighted, and SctO 2 standard deviation, were associated
with LOH (univariate analysis, P < 0.05). Two SmtO 2 indices (AUC and AUC
weighted), showed differences ( P < 0.05) between the patients with an LOH <=6
and >6 days, respectively. SmtO 2 , but not SctO 2 , indices improved the
adjusted R 2 for composite complications (+54.0%, P = 0.0001) and LOH (+19.0%, P
= 0.02) based on multiple linear models. Conclusions.: Muscular tissue
oxygenation has a stronger association with postoperative complications and
length of hospital stay than cerebral tissue oxygenation after major spine
surgery.
PMID- 28403401
TI - Determining the probability of a foreign body aspiration from history, symptoms
and clinical findings in children.
PMID- 28403402
TI - Feasibility and efficiency of a preoperative anaemia walk-in clinic: secondary
data from a prospective observational trial.
PMID- 28403403
TI - Objective model using only gender, age and medication list predicts in-hospital
morbidity after elective surgery.
AB - Background.: Most current surgical risk models contain many variables: some of
which may be esoteric, require a physician's assessment or must be obtained
intraoperatively. Early preoperative risk stratification is essential to identify
high risk, elective surgical patients for medical optimization and care
coordination across the perioperative period. We sought to create a simple,
patient-driven scoring system using: gender, age and list of medications to
predict in-hospital postoperative morbidity. We hypothesized that certain
medications would elevate risk, as indices of underlying conditions. Methods.:
Two Logistic regression models were created based on patient's gender, age, and
medications: GAMMA (Gender, age and type of medications to predict in-hospital
morbidity) and GAMMA-N (Gender, age and number of medications to predict in
hospital morbidity). A logistic regression models predicting in-hospital
morbidity based on ASA score alone was also created (ASA-M). The predictive
performance of these models was tested in a large surgical patient database.
Results.: Our GAMMA model predicts postoperative morbidity after perioperative
care with high accuracy (c-statistic 0.819, Brier score 0.034). This result is
similar to a model using only the ASA score (c-statistic 0.827, Brier score
0.033) and better than our GAMMA-N model (c-statistic 0.795, Brier score 0.050).
Conclusions.: The combination of a patient's gender, age, and medication list
provided reliable prediction of postoperative morbidity. Our model has the added
benefit of increased objectivity, can be conducted preoperatively, and is
amenable to patient-use as it requires only limited medical knowledge.
PMID- 28403404
TI - Hospital outcomes and long-term survival after referral to a specialized weaning
unit.
AB - Background.: Prolonged invasive mechanical ventilation (IMV) is a frequent
challenge, and an increasing number of patients are transferred from intensive
care units to long-term acute care hospitals or specialized weaning units. There
are few published data for discharge home rates, use of noninvasive ventilation
(NIV), or long-term survival. Methods.: A case-note and database review was
conducted of patients admitted to a UK national specialized weaning unit for
weaning from IMV between 1992 and 2012. Patients were grouped into diagnostic
categories according to the predominant cause of weaning failure. Weaning
outcomes and long-term survival were assessed according to diagnostic group and
mode of ventilation on discharge. Results.: Four hundred and fifty-eight patients
were transferred for weaning from IMV. Four hundred and seventeen (91%) survived
to hospital discharge, of whom at least 343 (82%) were ultimately discharged to
their own home. Three hundred and thirty (72%) weaned from IMV, of whom 142
weaned from all ventilation and 188 weaned to nocturnal NIV. Weaning success was
highest for patients with chronic obstructive pulmonary disease and chest wall
disorders. Median survival from unit discharge was 25 months (interquartile range
5-74), with the longest survival seen for patients discharged with nocturnal NIV
[37 (12-81) months]. Conclusions.: These results confirm successful weaning
outcomes for patients transferred to a specialized weaning and long-term
ventilation service. In contrast to other service models, most patients achieved
discharge to their own home.
PMID- 28403405
TI - Taking two steps at a time does not necessarily bring you forward! Monitoring
peripheral tissue perfusion with near-infrared spectroscopy.
PMID- 28403406
TI - Comparison of effectiveness of two commonly used two-handed mask ventilation
techniques on unconscious apnoeic obese adults.
AB - Background.: Mask ventilation and tracheal intubation are basic techniques for
airway management and mutually inclusive rescue measures to restore ventilation.
The aim of this study was to compare the effectiveness of mask ventilation
between two commonly used techniques of two-handed mask ventilation in obese
unconscious apnoeic adults. Methods.: Eighty-one obese adults received mask
ventilation after induction using C-E clamp and modified V-E clamp techniques in
a randomized crossover manner. Mechanical ventilation was provided using a
pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory
time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H 2 O. The
primary outcome was expired tidal volume. Results.: The BMI for the subjects was
37 ( sd 4.9) kg m -2 . The failure rates for mask ventilation (tidal
volume<=anatomical dead space) were 44% for the C-E technique and 0% for the V-E
technique ( P <0.001). Tidal volume was significantly lower for the C-E than the
V-E technique [371 ( sd 345) vs 720 (244) ml, P <0.001]. The peak airway
pressures were 21 ( sd 1.5) cm H 2 O for the C-E technique and 21 (1.3) cm H 2 O
for the V-E technique. Conclusions.: Mask ventilation using the modified V-E
technique is more effective than with the C-E technique in unconscious obese
apnoeic adults. Subjects who fail ventilation with the C-E technique can be
ventilated effectively with the V-E technique. Clinical trial registration.:
NCT02580526.
PMID- 28403407
TI - Apnoeic oxygenation in adults under general anaesthesia using Transnasal
Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) - a physiological
study.
AB - Background.: Apnoeic oxygenation during anaesthesia has traditionally been
limited by the rapid increase in carbon dioxide and subsequent decrease in pH.
Using a Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE)
technique a slower increase in carbon dioxide than earlier studies was seen.
Notably, apnoeic oxygenation using THRIVE has not been systematically evaluated
with arterial blood gases or in patients undergoing laryngeal surgery. The
primary aim of this study was to characterize changes in arterial P O 2 , P CO 2
and pH during apnoeic oxygenation using THRIVE under general anaesthesia.
Methods.: Adult patients, (ASA I-II), undergoing shorter laryngeal surgery under
general anaesthesia, were oxygenated during apnoea using THRIVE, 100% oxygen, 40
70 litres min - 1 . A cohort was randomized to hyperventilate during pre
oxygenation. Vital parameters and blood gases were monitored. Results.: Thirty
one patients, age 51 (34-76) yr, BMI 25 (4) were included. Mean apnoea time was
22.5 (4.5) min. Patients were well oxygenated, S pO 2 was never below 91%. The
increase in P aCO 2 and end-tidal CO 2 during apnoea was 0.24 (0.05) and 0.12
(0.04) kPa min -1 , respectively. Hyperventilation during pre-oxygenation
generated no difference in P aCO 2 at the end of apnoea compared with
normoventilation. Conclusions.: This physiological study of apnoeic oxygenation
using THRIVE during laryngeal surgery shows that this technique is able to keep
patients with mild systemic disease and a BMI <30 well oxygenated for a period of
up to 30 min. The THRIVE concept makes it possible to extend the apnoeic window
but monitoring of CO 2 and/or pH is recommended. Clinical trial registration.:
NCT02706431.
PMID- 28403408
TI - Systemic lidocaine fails to improve postoperative morphine consumption,
postoperative recovery and quality of life in patients undergoing posterior
spinal arthrodesis. A double-blind, randomized, placebo-controlled trial.
AB - Background.: It is inconclusive whether the perioperative administration of
systemic lidocaine provides effective postoperative analgesia and enhances
recovery in major orthopaedic surgery. We hypothesised that in adolescent and
adult patients undergoing posterior spinal arthrodesis, a perioperative lidocaine
infusion would reduce opioid requirements during the first 24 postoperative h.
Methods.: 70 patients undergoing posterior arthrodesis were enrolled in this
prospective, randomised, double-blind, placebo-controlled clinical trial.
Patients received total i.v. anaesthesia with propofol and remifentanil and were
randomized to an adjuvant therapy with either lidocaine [i.v.-bolus injection of
1.5 mg kg -1 at induction of anaesthesia, followed by an infusion of 1.5 mg kg -1
h -1 which was continued until six h after arrival at the post-anaesthesia care
unit] or placebo (equal volumes of saline). Postoperative pain was treated with
patient-controlled i.v. morphine. Primary endpoints of this study were morphine
requirements in the first postoperative 24 h. Results.: Systemic lidocaine did
not decrease morphine requirements in the first 24 postoperative h [lidocaine
group: 48 (23) mg (mean( sd )) vs placebo-group: 51(19) mg, P = 0.22]. Likewise,
groups were not different with respect to the severity of postoperative pain,
morphine consumption after 48 and 72 h, incidence of postoperative nausea and
vomiting, perioperative inflammation, time to recovery of intestinal function,
hospital length of stay, and quality of life (assessed preoperatively and one
month postoperatively using the SF-12 physical and mental composite scores).
Conclusions.: In our study, systemic lidocaine had no analgesic benefits in
posterior arthrodesis when added to an opioid-based anaesthetic regimen. Clinical
trial registration.: Eudra CT 2012-005264-98.
PMID- 28403409
TI - What do people expect of general anaesthesia?
PMID- 28403410
TI - Assessing the pathogenicity of RYR1 variants in malignant hyperthermia.
AB - Background: . Missense variants in the ryanodine receptor 1 gene ( RYR1 ) are
associated with malignant hyperthermia but only a minority of these have met the
criteria for use in predictive DNA diagnosis. We examined the utility of a
simplified method of segregation analysis and a functional assay for determining
the pathogenicity of recurrent RYR1 variants associated with malignant
hyperthermia. Methods: . We identified previously uncharacterised RYR1 variants
found in four or more malignant hyperthermia families and conducted simplified
segregation analyses. An efficient cloning and mutagenesis strategy was used to
express ryanodine receptor protein containing one of six RYR1 variants in HEK293
cells. Caffeine-induced calcium release, measured using a fluorescent calcium
indicator, was compared in cells expressing each variant to that in cells
expressing wild type ryanodine receptor protein. Results.: We identified 43
malignant hyperthermia families carrying one of the six RYR1 variants. There was
segregation of genotype with the malignant hyperthermia susceptibility phenotype
in families carrying the p.E3104K and p.D3986E variants, but the number of
informative meioses limited the statistical significance of the associations.
HEK293 functional assays demonstrated an increased sensitivity of RyR1 channels
containing the p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I compared with
wild type, but cells expressing p.D3986E had a similar caffeine sensitivity to
cells expressing wild type RyR1. Conclusions: . Segregation analysis is of
limited value in assessing pathogenicity of RYR1 variants in malignant
hyperthermia. Functional analyses in HEK293 cells provided evidence to support
the use of p.R2336H, p.R2355W, p.E3104K, p.G3990V and p.V4849I for diagnostic
purposes but not p.D3986E.
PMID- 28403411
TI - Comparison of bioreactance and echocardiographic non-invasive cardiac output
monitoring and myocardial function assessment in primagravida women.
AB - Background.: Non-invasive cardiac output monitoring (NICOM) using bioreactance
(BRT) in pregnancy is gaining interest but lacks validation. We compared
simultaneous cardiac output (CO) measurements obtained using the NICOM (r) (BRT
CO) and echocardiography (echo-CO), and assessed the relationship between
maternal characteristics and myocardial performance. Methods.: Paired stroke
volume (SV) and CO readings were obtained using NICOM (r) and echocardiography,
in a group of healthy nulliparous women throughout a 15 min period. Agreement
between NICOM (r) and echocardiography was assessed using Bland-Altman analysis
and the intraclass correlation coefficient (ICC). Left ventricular (LV) function
was assessed using systolic strain and tissue Doppler velocities (S', E', and A'
waves). Results.: Thirty-five women with a median [interquartile range] age,
weight, and gestation of 29 [26-34] yr, 71 [64-79] kg, and 28 [21-29] weeks,
respectively, were enrolled. There was good agreement between NICOM (r) -measured
and echocardiographically measured SV [mean bias 6 ml (limits of agreement -18 to
29); ICC 0.8 (95% confidence interval 0.6-0.9), P <0.001] and CO [mean bias 0.2
litres (limits of agreement -1.3-1.7); ICC 0.8 (95% confidence interval 0.7-0.9),
P <0.001; mean percentage error +/-26%; coefficient of error (precision)=3.4%].
The mean ( sd ) LV S' was 9.7 (2.3) cm s -1 . The mean ( sd ) LV strain was -18.6
(2.6)%. There was a negative relationship between BMI and LV diastolic function
measured using the E':A' ratio ( r = -0.51, P <0.01). Conclusions.: Stroke
volume and CO measurements obtained using NICOM (r) were comparable to those
obtained using echocardiography, with acceptable limits of agreement. Increased
maternal BMI negatively impacts LV diastolic function measured using tissue
Doppler imaging.
PMID- 28403412
TI - Reduced hemidiaphragmatic paresis with extrafascial compared with conventional
intrafascial tip placement for continuous interscalene brachial plexus block: a
randomized, controlled, double-blind trial.
AB - Background.: The incidence of hemidiaphragmatic paresis with continuous
interscalene brachial plexus block (CISB) can approach 100%. We tested the
hypothesis that extrafascial placement of the catheter tip reduces the rate of
hemidiaphragmatic paresis compared with intrafascial tip placement for CISB while
providing effective analgesia. Methods.: Seventy patients undergoing elective
major shoulder surgery under general anaesthesia were randomized to receive an
ultrasound-guided CISB plexus block for analgesia with the catheter tip placed
either within (intrafascial group) or immediately outside (extrafascial group)
the brachial plexus sheath midway between the levels of C5 and C6. Catheters were
bolus dosed with ropivacaine 0.5% 20 ml before surgery, followed by an infusion
of ropivacaine 0.2% at 4 ml h -1 for the first 2 days after surgery. The primary
outcome was hemidiaphragmatic paresis measured by M-mode ultrasonography on
postoperative day (POD) 1. Secondary outcomes included forced vital capacity,
forced expiratory volume in 1 s, and rest pain scores. Results.: The incidence of
hemidiaphragmatic paresis on POD 1 was significantly reduced in the extrafascial
group {intrafascial, 41% [95% confidence interval (CI) 25-59%]; extrafascial, 15%
(95% CI 5-32%); P =0.01}. We were unable to detect a difference between groups in
any of the functional respiratory outcomes or in rest pain scores [numerical
rating scale (1-10): intrafascial, 3 (95% CI 2-3); extrafascial, 3 (95% CI: 2-4);
P =0.93] on POD 1. Conclusions.: Placement of the catheter tip immediately
outside of the brachial plexus sheath reduced the incidence of hemidiaphragmatic
paresis on POD 1 associated with ultrasound-guided CISB while providing effective
analgesia after major shoulder surgery. Our results do not support the routine
placement of the catheter tip within the brachial plexus sheath for CISB.
Clinical trial registration.: NCT02433561.
PMID- 28403413
TI - Can tongue thickness measured by ultrasonography predict difficult tracheal
intubation?
AB - Background.: Increased tongue thickness is likely to be associated with difficult
airways. However, no methods to evaluate tongue thickness were available.
Currently, tongue thickness can be measured by ultrasonography. The present study
investigated the predictive value of tongue thickness to predict difficult
tracheal intubation. Methods.: Adult patients undergoing tracheal intubation and
general anaesthesia were enrolled in the study. Tongue thickness was assessed
using submental ultrasonography in the median sagittal plane before anaesthesia.
Airway assessments were conducted. Ratios of tongue thickness to thyromental
distance were calculated to investigate the potential predictive value of their
combination. The primary outcome was difficult tracheal intubation. A
multivariable logistic regression and receiver operating characteristic curve
analysis were used. Results.: In total, 2254 patients were analysed. One hundred
and forty-two (6.3%) patients experienced difficult laryngoscopy, and 51 (2.3%)
patients experienced difficult tracheal intubation. Increased tongue thickness
(>6.1 cm) was an independent predictor for difficult tracheal intubation
[sensitivity 0.75, 95% confidence interval (CI) 0.60-0.86; specificity 0.72, 95%
CI 0.70-0.74]. An area under the curve of 0.78 (95% CI 0.77-0.80) for predicting
difficult tracheal intubation was calculated. Increased ratios of tongue
thickness to thyromental distance (>0.87) presented a considerable area under the
curve (0.86, 95% CI 0.84-0.87), sensitivity (0.84, 95% CI 0.71-0.93), and
specificity (0.79, 95% CI 0.77-0.81). Conclusions.: Tongue thickness measured by
ultrasonography and its ratio to thyromental distance present significant
capacities to predict difficult tracheal intubation. Clinical trial
registration.: ChiCTR-RCS-14004539.
PMID- 28403414
TI - A national survey of videolaryngoscopy in the United Kingdom.
AB - Background.: There are increasing numbers of videolaryngoscopes marketed and
increasing interest in the technology. The Difficult Airway Society's 2015
guidelines recommend that videolaryngoscopes should be immediately available at
all times and that all anaesthetists should be trained and skilled in their use.
Methods.: An electronic survey was sent to all UK National Health Service
hospitals to examine availability, use, and attitudes to videolaryngoscopy, and
closed in January 2014. Results.: The return rate was 67%. Videolaryngoscopy was
available in 91% of operating theatres, ~50% of intensive care units (ICUs) and
obstetric theatres, with lower availability in emergency departments (EDs),
paediatric anaesthesia, and independent sector hospitals. The most widely
available devices were the Airtraq, the GlideScope, and C-MAC. Approximately one
in seven respondents reported availability of videolaryngoscopy in all clinical
areas. Most departments imposed restrictions on videolaryngoscopy use, especially
the ICU and ED. Device selection was only infrequently based on published
literature or formal trial. Structured introduction of videolaryngoscopy into
practice was uncommon. Penetration of videolaryngoscopy was highly variable;
fewer than a third reported widespread use or enthusiasm, although this increased
where the C-MAC and GlideScope were widely available. Conclusions.:
Videolaryngoscopy is available in most hospitals' main operating departments, but
in fewer than half of other locations. There is marked variation in device,
methods of introduction, usage, and clinical adoption. Most hospitals need to
change practice to comply with current guidelines. Selection and implementation
vary widely.
PMID- 28403415
TI - Enhanced recovery after surgery for hip and knee arthroplasty: where is the
evidence?
PMID- 28403416
TI - Comparison of video-based learning and lecture-based learning for training of
ultrasound-guided central venous catheterization: a randomized controlled trial.
PMID- 28403417
TI - Administration of blood products to prevent bleeding complications associated
with central venous catheter insertion in patients at risk: a systematic review.
PMID- 28403418
TI - Pain assessment in conscious healthy volunteers: a crossover study evaluating the
analgesia/nociception index.
PMID- 28403419
TI - Evaluation of non-specific symptoms after anaesthesia.
PMID- 28403420
TI - Ice pops in the recovery room: effects on postoperative nausea and vomiting.
PMID- 28403421
TI - Reply: allostatic load as an approach to support the theoretical assumptions of
the Brief Measure of Emotional Preoperative Stress (B-MEPS).
PMID- 28403422
TI - Hypoglycaemia after accidental ocular insulin injection.
PMID- 28403423
TI - Rainbow after the storm.
PMID- 28403424
TI - Maternal convulsion during high-dose sevoflurane anaesthesia for open foetal
surgery.
PMID- 28403425
TI - Lights! Oxygen! Action! Hollywood anaesthesia is coming to a theatre near you.
PMID- 28403426
TI - High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in
Heteroplasmic Leber's Hereditary Optic Neuropathy (LHON).
AB - Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease
that typically causes bilateral blindness in young men. It is characterized by as
yet undisclosed genetic and environmental factors affecting the incomplete
penetrance. Methods: We identified 27 LHON subjects who possess heteroplasmic
primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
Results: The presence of centrocecal scotoma, an edematous, hyperemic optic nerve
head, and vascular tortuosity, as well as telangiectasia was recognized in
affected subjects. We found higher cellular mtDNA content in peripheral blood
cells of unaffected heteroplasmic mutation carriers with respect to the affected.
Conclusions: The increase of cellular mtDNA content prevents complete loss of
vision despite the presence of a heteroplasmic state of LHON primary mutation,
suggesting that it is a key factor responsible for penetrance of LHON.
PMID- 28403427
TI - New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults.
AB - Importance: Despite increased focus on reducing opioid prescribing for long-term
pain, little is known regarding the incidence and risk factors for persistent
opioid use after surgery. Objective: To determine the incidence of new persistent
opioid use after minor and major surgical procedures. Design, Setting, and
Participants: Using a nationwide insurance claims data set from 2013 to 2014, we
identified US adults aged 18 to 64 years without opioid use in the year prior to
surgery (ie, no opioid prescription fulfillments from 12 months to 1 month prior
to the procedure). For patients filling a perioperative opioid prescription, we
calculated the incidence of persistent opioid use for more than 90 days among
opioid-naive patients after both minor surgical procedures (ie, varicose vein
removal, laparoscopic cholecystectomy, laparoscopic appendectomy,
hemorrhoidectomy, thyroidectomy, transurethral prostate surgery,
parathyroidectomy, and carpal tunnel) and major surgical procedures (ie, ventral
incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and
hysterectomy). We then assessed data for patient-level predictors of persistent
opioid use. Main Outcomes and Measures: The primary outcome was defined a priori
prior to data extraction. The primary outcome was new persistent opioid use,
which was defined as an opioid prescription fulfillment between 90 and 180 days
after the surgical procedure. Results: A total of 36 177 patients met the
inclusion criteria, with 29 068 (80.3%) receiving minor surgical procedures and
7109 (19.7%) receiving major procedures. The cohort had a mean (SD) age of 44.6
(11.9) years and was predominately female (23 913 [66.1%]) and white (26 091
[72.1%]). The rates of new persistent opioid use were similar between the 2
groups, ranging from 5.9% to 6.5%. By comparison, the incidence in the
nonoperative control cohort was only 0.4%. Risk factors independently associated
with new persistent opioid use included preoperative tobacco use (adjusted odds
ratio [aOR], 1.35; 95% CI, 1.21-1.49), alcohol and substance abuse disorders
(aOR, 1.34; 95% CI, 1.05-1.72), mood disorders (aOR, 1.15; 95% CI, 1.01-1.30),
anxiety (aOR, 1.25; 95% CI, 1.10-1.42), and preoperative pain disorders (back
pain: aOR, 1.57; 95% CI, 1.42-1.75; neck pain: aOR, 1.22; 95% CI, 1.07-1.39;
arthritis: aOR, 1.56; 95% CI, 1.40-1.73; and centralized pain: aOR, 1.39; 95% CI,
1.26-1.54). Conclusions and Relevance: New persistent opioid use after surgery is
common and is not significantly different between minor and major surgical
procedures but rather associated with behavioral and pain disorders. This
suggests its use is not due to surgical pain but addressable patient-level
predictors. New persistent opioid use represents a common but previously
underappreciated surgical complication that warrants increased awareness.
PMID- 28403428
TI - Maternal and Fetal Outcomes of Admission for Delivery in Women With Congenital
Heart Disease.
AB - Background: Women with congenital heart disease (CHD) may be at increased risk
for adverse events during pregnancy and delivery. Objective: To compare delivery
outcomes between women with and without CHD. Design, Setting, and Participants:
This retrospective study of inpatient delivery admissions in the Healthcare Cost
and Utilization Project's California State Inpatient Database compared maternal
and fetal outcomes between women with and without CHD by using multivariate
logistic regression. Female patients with codes for delivery from the
International Classification of Diseases, Ninth Revision, from January 1, 2005,
through December 31, 2011, were included. The association of CHD with readmission
was assessed to 7 years after delivery. Cardiovascular morbidity and mortality
were hypothesized to be higher among women with CHD. Data were analyzed from
April 4, 2014, through January 23, 2017. Exposures: Noncomplex and complex CHD.
Main Outcomes and Measures: Maternal outcomes included in-hospital arrhythmias,
eclampsia or preeclampsia, congestive heart failure (CHF), length of stay,
preterm labor, anemia complicating pregnancy, placental abnormalities, infection
during labor, maternal readmission at 1 year, and in-hospital mortality. Fetal
outcomes included growth restriction, distress, and death. Results: Among 3 642
041 identified delivery admissions, 3189 women had noncomplex CHD (mean [SD] age,
28.6 [7.6] years) and 262 had complex CHD (mean [SD] age, 26.5 [6.8] years).
Women with CHD were more likely to undergo cesarean delivery (1357 [39.3%] vs 1
164 509 women without CHD [32.0%]; P < .001). Incident CHF, atrial arrhythmias,
ventricular arrhythmias, and maternal mortality were uncommon during
hospitalization, with each occurring in fewer than 10 women with noncomplex or
complex CHD (<0.5% each). After multivariate adjustment, noncomplex CHD (odds
ratio [OR], 9.7; 95% CI, 4.7-20.0) and complex CHD (OR, 56.6; 95% CI, 17.6-182.5)
were associated with greater odds of incident CHF. Similar odds were found for
atrial arrhythmias in noncomplex (OR, 8.2; 95% CI, 3.0-22.7) and complex (OR,
31.8; 95% CI, 4.3-236.3) CHD, for fetal growth restriction in noncomplex (OR,
1.6; 95% CI, 1.3-2.0) and complex (OR, 3.5; 95% CI, 2.1-6.1) CHD, and for
hospital readmission in both CHD groups combined (OR, 3.6; 95% CI, 3.3-4.0).
Complex CHD was associated with greater adjusted odds of serious ventricular
arrhythmias (OR, 31.8; 95% CI, 4.3-236.3) and maternal in-hospital mortality (OR,
79.1; 95% CI, 23.9-261.8). Conclusions and Relevance: In this study of hospital
admissions for delivery in California, CHD was associated with incident CHF,
atrial arrhythmias, and fetal growth restriction and complex CHD was associated
with ventricular arrhythmias and maternal in-hospital mortality, although these
outcomes were rare, even in women with complex CHD. These findings may guide
monitoring decisions and risk assessment for pregnant women with CHD at the time
of delivery.
PMID- 28403429
TI - The Use of High-Resolution Metabolomics in Occupational Exposure and Health
Research.
PMID- 28403430
TI - Corrigendum.
PMID- 28403431
TI - Differences Between Women With Traumatic and Idiopathic Chronic Neck Pain and
Women Without Neck Pain: Interrelationships Among Disability, Cognitive Deficits,
and Central Sensitization.
AB - Background: To date, a clear differentiation of disability, cognitive deficits,
and central sensitization between chronic neck pain of a traumatic nature and
that of a nontraumatic nature is lacking. Objective: This study aimed to examine
differences in disability, cognitive deficits, and central sensitization between
women with traumatic and idiopathic (nontraumatic) chronic neck pain and women
who were healthy. In addition, interrelationships among these variables were
investigated. Design: This was a case-control study. Methods: Ninety-five women
(28 women who were healthy [controls], 35 women with chronic idiopathic neck pain
[CINP], and 32 women with chronic whiplash-associated disorders [CWAD]
[traumatic]) were enrolled in the study. First, all participants completed
standardized questionnaires to investigate pain-related disability and health
related quality of life. Next, cognitive performance was assessed. Finally,
pressure pain thresholds and conditioned pain modulation were examined to
investigate central sensitization. Results: Pain-related disability, reduced
health-related quality of life, and cognitive deficits were present in
participants with CWAD and, to a significantly lesser extent, in participants
with CINP. Local hyperalgesia was demonstrated in participants with CWAD and CINP
but not in women who were healthy. However, distant hyperalgesia and decreased
conditioned pain modulation efficacy were shown only in participants with CWAD;
this result is indicative of the presence of central sensitization. Moderate to
strong Spearman correlations (rho=.456-.701) among disability, cognitive
deficits, and hyperalgesia (local and distant) were observed in participants with
CWAD. In participants with CINP, only local hyperalgesia and subjective cognitive
deficits were moderately (rho=.463) correlated. Limitations: No conclusions about
the causality of the observed correlations can be drawn. Conclusions: This
innovative research revealed important differences between women with CWAD and
women with CINP and thus provided evidence of the clinical importance of
distinguishing the assessment and rehabilitation approaches for both pain
conditions.
PMID- 28403432
TI - Physical Therapy and the Global HIV/AIDS Pandemic.
PMID- 28403433
TI - Negative Psychosis Prevention Trials.
PMID- 28403435
TI - Hospital Admissions for Myocardial Infarction and Stroke Before and After the
Trans-Fatty Acid Restrictions in New York.
AB - Importance: Trans-fatty acids (TFAs) have deleterious cardiovascular effects.
Restrictions on their use were initiated in 11 New York State (NYS) counties
between 2007 and 2011. The US Food and Drug Administration plans a nationwide
restriction in 2018. Public health implications of TFA restrictions are not well
understood. Objective: To determine whether TFA restrictions in NYS counties were
associated with fewer hospital admissions for myocardial infarction (MI) and
stroke compared with NYS counties without restrictions. Design, Setting, and
Participants: We conducted a retrospective observational pre-post study of
residents in counties with TFA restrictions vs counties without restrictions from
2002 to 2013 using NYS Department of Health's Statewide Planning and Research
Cooperative System and census population estimates. In this natural experiment,
we included those residents who were hospitalized for MI or stroke. The data
analysis was conducted from December 2014 through July 2016. Exposure: Residing
in a county where TFAs were restricted. Main Outcomes and Measures: The primary
outcome was a composite of MI and stroke events based on primary discharge
diagnostic codes from hospital admissions in NYS. Admission rates were calculated
by year, age, sex, and county of residence. A difference-in-differences
regression design was used to compare admission rates in populations with and
without TFA restrictions. Restrictions were only implemented in highly urban
counties, based on US Department of Agriculture Economic Research Service Urban
Influence Codes. Nonrestriction counties of similar urbanicity were chosen to
make a comparison population. Temporal trends and county characteristics were
accounted for using fixed effects by county and year, as well as linear time
trends by county. We adjusted for age, sex, and commuting between restriction and
nonrestriction counties. Results: In 2006, the year before the first restrictions
were implemented, there were 8.4 million adults (53.6% female) in highly urban
counties with TFA restrictions and 3.3 million adults (52.3% female) in highly
urban counties without restrictions. Twenty-five counties were included in the
nonrestriction population and 11 in the restriction population. Three or more
years after restriction implementation, the population with TFA restrictions
experienced significant additional decline beyond temporal trends in MI and
stroke events combined (-6.2%; 95% CI, -9.2% to -3.2%; P < .001) and MI (-7.8%;
95% CI, -12.7% to -2.8%; P = .002) and a nonsignificant decline in stroke (-3.6%;
95% CI, -7.6% to 0.4%; P = .08) compared with the nonrestriction populations.
Conclusions and Relevance: The NYS populations with TFA restrictions experienced
fewer cardiovascular events, beyond temporal trends, compared with those without
restrictions.
PMID- 28403434
TI - Expanding the Genotypic Spectrum of Bathing Suit Ichthyosis.
AB - Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of
keratinization characterized by restriction of scale to sites of relatively
higher temperature such as the trunk, with cooler areas remaining unaffected.
Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis
is caused by recessive, temperature-sensitive mutations in the transglutaminase-1
gene (TGM1). Clear genotype-phenotype correlations have been difficult to
establish because several of the same TGM1 mutations have been reported in BSI
and other forms of congenital ichthyosis. We identify novel and recurrent
mutations in 16 participants with BSI. Objective: To expand the genotypic
spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to
use BSI genotypes to draw inferences about the temperature sensitivity of TGM1
mutations. Design, Setting, and Participants: A total of 16 participants with BSI
from 13 kindreds were identified from 6 academic medical centers. A detailed
clinical history was obtained from each participant, including phenotypic
presentation at birth and disease course. Each participant underwent targeted
sequencing of TGM1. Main Outcomes and Measures: Phenotypic and genotypic
characteristics in these patients from birth onward. Results: Of the 16
participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39
years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8
TGM1 missense mutations that to our knowledge have not been previously reported
in BSI: 5 have been previously described in non-temperature-sensitive forms of
congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and
Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations.
Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating
that these mutations are temperature sensitive. Seven of 10 probands with a
compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315,
providing evidence that mutations at these sites are temperature sensitive and
highlighting the importance of these residues in the pathogenesis of BSI.
Conclusions and Relevance: Our findings expand the genotypic spectrum of BSI and
the understanding of temperature sensitivity of TGM1 mutations. Increased
awareness of temperature-sensitive TGM1 genotypes should aid in genetic
counseling and provide insights into the pathophysiology of TGM1 ichthyoses,
transglutaminase-1 enzymatic activity, and potential therapeutic approaches.
PMID- 28403436
TI - Acute Large-Bowel Obstruction in an Institutionalized Man.
PMID- 28403439
TI - Advances in Vector Control Science: Rear-and-Release Strategies Show Promise...
but Don't Forget the Basics.
AB - Both chikungunya and Zika viruses have recently swept from Africa across the
Pacific to the Americas, causing major outbreaks of disease in humans. In the
meantime, dengue epidemics continue throughout the tropics. Traditional vector
control programs based on strategies from 1950s and 1960s have been relatively
ineffective in combating recent epidemics. In response, new methods involving the
rearing and releasing of large numbers of mosquitoes to eliminate or modify local
Aedes populations are being developed, with several currently conducting field
releases in high-risk countries. These advances, include the release of Wolbachia
infected Aedes aegypti and Aedes albopictus, for either its virus-blocking
capabilities, sterilization by cytoplasmic incompatibility, or both; the release
of Aedes carrying dominant lethal genes, such as the OX513A strain of A. aegypti;
and other emerging techniques, such as advancing gene-drive technologies, are
summarized, as well as current stages of development and primary operational and
regulatory hurdles. Although these technologies show great promise, none are
ready for widespread rollout for cities of millions of people. Thus, efforts
should be made to avoid methods such as space sprays that have failed and improve
existing technologies to increase their efficacy.
PMID- 28403438
TI - Current Status of Dengue Therapeutics Research and Development.
AB - Dengue is a significant global health problem. Even though a vaccine against
dengue is now available, which is a notable achievement, its long-term protective
efficacy against each of the 4 dengue virus serotypes remains to be definitively
determined. Consequently, drugs directed at the viral targets or critical host
mechanisms that can be used safely as prophylaxis or treatment to effectively
ameliorate disease or reduce disease severity and fatalities are still needed to
reduce the burden of dengue. This review will provide a brief account of the
status of therapeutics research and development for dengue.
PMID- 28403437
TI - Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness
Caused by Mutations in the GUCY2D Gene.
AB - Purpose: To examine how severe congenital blindness resulting from mutations of
the GUCY2D gene alters brain structure and function, and to relate these findings
to the notable preservation of retinal architecture in this form of Leber
congenital amaurosis (LCA). Methods: Six GUCY2D-LCA patients (ages 20-46) were
studied with optical coherence tomography of the retina and multimodal magnetic
resonance imaging (MRI) of the brain. Measurements from this group were compared
to those obtained from populations of normally sighted controls and people with
congenital blindness of a variety of causes. Results: Patients with GUCY2D-LCA
had preservation of the photoreceptors, ganglion cells, and nerve fiber layer.
Despite this, visual function in these patients ranged from 20/160 acuity to no
light perception, and functional MRI responses to light stimulation were
attenuated and restricted. This severe visual impairment was reflected in
substantial thickening of the gray matter layer of area V1, accompanied by an
alteration of resting-state correlations within the occipital lobe, similar to a
comparison group of congenitally blind people with structural damage to the
retina. In contrast to the comparison blind population, however, the GUCY2D-LCA
group had preservation of the size of the optic chiasm, and the fractional
anisotropy of the optic radiations as measured with diffusion tensor imaging was
also normal. Conclusions: These results identify dissociable effects of blindness
upon the visual pathway. Further, the relatively intact postgeniculate white
matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of
visual function with gene augmentation therapy.
PMID- 28403441
TI - Clinical and Laboratory Diagnosis of Dengue Virus Infection.
AB - Infection with any of the 4 dengue virus serotypes results in a diverse range of
symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever
and shock. Given that dengue virus infection elicits such a broad range of
clinical symptoms, early and accurate laboratory diagnosis is essential for
appropriate patient management. Virus detection and serological conversion have
been the main targets of diagnostic assessment for many years, however cross
reactivity of antibody responses among the flaviviruses has been a confounding
issue in providing a differential diagnosis. Furthermore, there is no single,
definitive diagnostic biomarker that is present across the entire period of
patient presentation, particularly in those experiencing a secondary dengue
infection. Nevertheless, the development and commercialization of point-of-care
combination tests capable of detecting markers of infection present during
different stages of infection (viral nonstructural protein 1 and immunoglobulin
M) has greatly simplified laboratory-based dengue diagnosis. Despite these
advances, significant challenges remain in the clinical management of dengue
infected patients, especially in the absence of reliable biomarkers that provide
an effective prognostic indicator of severe disease progression. This review
briefly summarizes some of the complexities and issues surrounding clinical
dengue diagnosis and the laboratory diagnostic options currently available.
PMID- 28403443
TI - The Use of Ivy in Dermatology.
PMID- 28403440
TI - Case Management of Dengue: Lessons Learned.
AB - The global burden of dengue and its geographic distribution have increased over
the past several decades. The introduction of dengue in new areas has often been
accompanied by high case-fatality rates. Drawing on the experience in managing
dengue cases at the Queen Sirikit National Institute of Child Health in Bangkok,
Thailand, this article provides the authors' perspectives on key clinical lessons
to improve dengue-related outcomes. Parallels between this clinical experience
and outcomes reported in randomized controlled trials, results of efforts to
disseminate practice recommendations, and suggestions for areas for further
research are also discussed.
PMID- 28403444
TI - Wicked Cures for the Warty-A Historical Perspective.
PMID- 28403445
TI - Oribasius-Pediatric Skin Eruptions and the Origins of the Allergic Reaction to
Breast Milk.
PMID- 28403446
TI - Beauty Patches.
PMID- 28403448
TI - Pregnancy in Adult Congenital Heart Disease: Special Delivery.
PMID- 28403449
TI - Inaccurate Claims About VA Surgical Quality Might Mislead Veterans-Reply.
PMID- 28403450
TI - Estimated Cost of Emergency Sunburn Visits-Validation of ICD-9-CM Search
Criteria.
PMID- 28403452
TI - Negative Psychosis Prevention Trials-Reply.
PMID- 28403451
TI - The Lung Microbiome: Key to Respiratory Ills?
PMID- 28403453
TI - Profile of Maternal Smokers Who Quit During Pregnancy: A Population-Based Cohort
Study of Tasmanian Women, 2011-2013.
AB - Introduction: Smoking remains the single-most significant preventable cause of
poor pregnancy outcomes, yet around 12% of Australian women smoke during
pregnancy. Many women are motivated to quit when they find out they are pregnant,
yet few are successful. While previous studies have examined the profile of the
maternal smoker compared to her nonsmoking counterpart (Aim 1), little is known
about what differentiates women who quit during pregnancy to those who do not
(Aim 2). Here, we present results from a study investigating the characteristics
of women who were able to quit during pregnancy. Methods: Data were drawn from
the Tasmanian Population Health database of women who had received antenatal care
between 2011 and 2013 (n = 14300). Data collected included age, relationship
status and ethnicity of expectant mothers, antenatal details, mental health
conditions, and drug use. Independent samples t tests were used to compare
differences between women who had, and those who had not, quit during pregnancy.
The 19.4% of women who self-reported as smoking in the first half (first 20
weeks) of their pregnancy were further grouped and analyzed comparing those who
reported still smoking in the second half of their pregnancy (smokers: n = 2570,
92.4%) to those who quit (quitters: n = 211, 7.6%). Results: Quitters (57.8%)
were more likely to be in a relationship than their non-quitting counterparts
(49.6%, p = .022) and were less likely to suffer from postnatal depression (2.4%
vs. 6.0%, p = .029). No other differences between quitters and smokers were
observed. Conclusions: Determining the profile of women who are able to quit
during pregnancy may be important to improve the relatively poor cessation rates
among maternal smokers and may assist in more effectively targeting at-risk
women. Implications: Smoking cessation interventions have traditionally targeted
socially disadvantaged women, for good reason: the majority of smoking pregnant
women fall into this category. However, despite the significant attention and
resources dedicated to antenatal smoking cessation interventions, most are
ineffective with only 7.6% of the present sample quitting smoking during
pregnancy. This paper may assist in developing more effective antenatal smoking
cessation interventions by more clearly describing the profile of maternal
smokers who successfully quit during pregnancy. Specifically, this paper
highlights the need to acknowledge and address women's relationship status and
mental health in order to promote smoking cessation in pregnancy.
PMID- 28403454
TI - Correlates of Electronic Cigarettes Use Before and During Pregnancy.
AB - Introduction: Electronic cigarette use is rapidly gaining in popularity. However,
little is known about correlates and reasons for electronic cigarette use by
women of reproductive age, a group for which the safety and efficacy of
electronic cigarette use is of particular interest. Methods: As part of a
clinical trial for smoking cessation, we surveyed pregnant smokers about their
lifetime use of electronic cigarettes, previous use of any adjunctive treatments
for smoking cessation, and use of electronic cigarettes during pregnancy. We
examined associations between electronic cigarette use and participant
characteristics. Results: Fifty-three percent (55/103) of participants had
previously tried electronic cigarettes. Ever users smoked more cigarettes per day
before pregnancy (p = .049), had a greater number of previous quit attempts (p =
.033), and were more likely to identify as being Hispanic or non-Hispanic white
than never users (p = .027). Fifteen percent of participants (15/103) reported
previous use of electronic cigarettes for smoking cessation, which was more
common than the use of any specific FDA-approved smoking cessation medication.
Fourteen percent of participants (14/103) reported electronic cigarette use
during pregnancy, most commonly to quit smoking. A history of substance abuse (p
= .043) and more previous quit attempts (p = .018) were associated with
electronic cigarette use during pregnancy. Conclusions: Use of electronic
cigarettes to quit smoking may be common in women of reproductive age, including
those who are pregnant. More research is needed to determine the risks and
benefits of electronic cigarette use in this population of smokers. Implications:
This study shows that electronic cigarettes are used by women of reproductive
age, including pregnant smokers. The implications of this finding are that there
is an urgent need to examine the risks and benefits of electronic cigarette use,
especially by pregnant women. The study also shows that electronic cigarettes are
commonly used as a smoking cessation aid in women of reproductive age. The
greater likelihood of electronic cigarette use compared to proven adjunctive
smoking treatments suggests that electronic cigarettes should be examined as a
potential aid to cessation in this population.
PMID- 28403455
TI - Maternal Active Smoking During Pregnancy and Low Birth Weight in the Americas: A
Systematic Review and Meta-analysis.
AB - Introduction: Smoking during pregnancy may negatively impact newborn birth
weight. This study investigates the relationship between maternal active smoking
during pregnancy and low birth weight in the Americas through systematic review
and meta-analysis. Methods: A literature search was conducted through indexed
databases and the grey literature. Case-control and cohort studies published
between 1984 and 2016 conducted within the Americas were included without
restriction regarding publication language. The article selection process and
data extraction were performed by two independent investigators. A meta-analysis
of random effects was conducted, and possible causes of between-study
heterogeneity were evaluated by meta-regressions and subgroup analyses.
Publication bias was assessed by visual inspection of Begg's funnel plot and by
Egger's regression test. Results: The literature search yielded 848 articles from
which 34 studies were selected for systematic review and 30 for meta-analysis.
Active maternal smoking was associated with low birth weight, OR = 2.00 (95% CI:
1.77-2.26; I2 = 66.3%). The funnel plot and Egger's test (p = .14) indicated no
publication bias. Meta-regression revealed that sample size, study quality, and
the number of confounders in the original studies did not account for the between
study heterogeneity. Subgroup analysis indicated no significant differences when
studies were compared by design, sample size, and regions of the Americas.
Conclusion: Low birth weight is associated with maternal active smoking during
pregnancy regardless of the region in the Americas or the studies' methodological
aspects. Implications: A previous search of the major electronic databases
revealed that no studies appear to have been conducted to summarize the
association between maternal active smoking during pregnancy and low birth weight
within the Americas. Therefore, this systematic review may help to fill the
information gap. The region of the Americas contains some of the most populous
countries in the world; therefore, this study may provide useful data from this
massive segment of the world's population.
PMID- 28403456
TI - National Survey of Smoking and Smoking Cessation Education Within UK Midwifery
School Curricula.
AB - Introduction: Smoking in pregnancy in the United Kingdom remains prevalent (11%).
To encourage and support pregnant smokers to quit, midwives must be adequately
trained to do so. Substantial curricular gaps have been identified in the smoking
cessation training of medical, nursing, and optometry schools. This study aimed
to identify the extent of smoking cessation training and assessment in UK
midwifery schools. Methods: All UK undergraduate midwifery schools (n = 53) were
invited to complete a web-based survey of their curricular coverage and
assessment related to smoking cessation, and perceived barriers to delivering
smoking cessation training. Results: Twenty-nine (55%) midwifery schools
responded. Most teaching was completed in the initial year of study. All reported
teaching the harmful effects of tobacco use. The majority of respondents (83%)
reported training students in brief intervention delivery and ways to assist quit
attempts. Only 24% of schools in this study included relapse prevention in their
curriculum. The most frequently reported barriers to teaching smoking cessation
were "lack of knowledge amongst staff" (17%), "no space in a crowded curriculum"
(17%), and "administrative problems" (13%). Conclusions: Midwifery schools are
teaching the harmful effects of smoking and providing training on brief
interventions. However, in some schools student midwives are not being
sufficiently trained on relapse prevention or assessed in the practical skills
necessary for delivering evidence-based interventions. Implications: Midwifery
schools should revise the content and delivery of smoking cessation training to
ensure midwives are equipped with the necessary knowledge and skills to
contribute to the challenge of smoking cessation in pregnancy.
PMID- 28403457
TI - Smoking Cessation Support by Text Message During Pregnancy: A Qualitative Study
of Views and Experiences of the MiQuit Intervention.
AB - Introduction: SMS text messaging is increasingly used for delivering smoking
cessation support and pilot studies suggest this may also be useful in pregnancy.
This study explores the views of women who received a tailored text messaging
cessation intervention (MiQuit) during pregnancy, focusing on acceptability,
perceived impact, and suggestions for improvements. Methods: Semi-structured
interviews were undertaken with 15 purposively sampled women who had received the
MiQuit intervention during pregnancy as part of a randomized controlled trial.
Data were analyzed thematically. Results: Three main themes were identified:
"impact", "approach," and "optimization." Participants described an immediate,
yet often short-lived, impact from the texts that distracted and delayed them
from smoking and they perceived that texts focusing on the development of and
risk to the baby generated more enduring emotional impacts. Most women found
receiving support by text preferable to face-to-face cessation support, with
participants citing the greater regularity, convenience, and non-judgmental style
as particular advantages. Participants would have preferred a longer support
program with increased tailoring, greater customization of text timings and
consideration of cutting down as an alternative/precursor to quitting.
Conclusion: Pregnancy-specific cessation support by text message was well
received and participants considered the support increased their motivation to
stop smoking. The focus on the developing baby, the regularity of contact and the
provision of gentle, encouraging messages were highlighted as particularly
important elements of the program. Implications: This study adds further evidence
to the acceptability and perceived positive impact of text-messaging programs in
aiding smoking cessation in pregnancy. The findings indicate that for some women,
this type of support is preferable to face-to-face methods and could be utilized
by health professionals, either in addition to current methods or as an
alternative. This study is also relevant to researchers developing health-related
text programs to consider participants' desire for greater tailoring. Further
research is required into adapting and continuing text support for women
postpartum.
PMID- 28403458
TI - Cognitive and Behavioral Predictors of Quit Attempts and Biochemically-Validated
Abstinence During Pregnancy.
AB - Introduction: Initiating a quit attempt and achieving abstinence are distinct
behaviors that have distinct correlates in general smokers. Studies predicting
prenatal smoking have not addressed this. Methods: Pregnant smokers (N = 207),
recruited to a cessation intervention trial, were used as an observational
cohort. Women completed measures at baseline and 12-week follow-up (mid-late
pregnancy). Outcomes were having made at least one quit attempt since baseline,
and cotinine-validated 7-day abstinence at follow-up in attempters. Baseline
predictors included demographics (age, deprivation, partner's smoking), smoking
behaviors (nicotine dependence, quit attempt history, previous prenatal smoking),
and smoking beliefs (self-efficacy, determination, intention to quit, nonsmoker
identity, social support, pregnancy-outcome beliefs). For each outcome, variables
reaching p < .1 in logistic regression analyses were entered into a multivariate
model controlling for trial arm. A complete case analysis was undertaken, with
missing data assumptions tested in sensitivity analyses. Results: One hundred
seventy-five women (85%) completed follow-up. Intention and determination to quit
(p < .001), self-efficacy, nonsmoker identity, and not having previously smoked
in pregnancy (p < .05) were univariate predictors of making a quit attempt, with
stronger intention to quit the only independent predictor (multivariate odds
ratio [OR] = 2.41, 95% confidence interval [CI] 1.19-4.87). Only nicotine
dependence predicted validated abstinence among those who made a quit attempt
(multivariate OR = 0.25, 95% CI 0.10-0.60). Conclusions: Initiating a quit
attempt and achieving abstinence during pregnancy were found to have different
correlates. For women yet to make a quit attempt in their pregnancy, smoking
beliefs may be important intervention targets, but once they are engaged in
quitting, nicotine dependence appears of prime importance. Implications: This
study suggests that cognitive, particularly motivational, variables predict
whether pregnant smokers will make a quit attempt, but they do not predict
successful abstinence in those who attempt to quit, where nicotine dependence
dominates. Interventions should facilitate quit attempts by targeting
motivational variables among pregnant women who continue to smoke, but should
focus on managing withdrawal once a woman initiates a quit attempt.
PMID- 28403459
TI - The Influence of Smoking on Breast feeding Among Women Who Quit Smoking During
Pregnancy.
AB - Introduction: Understanding factors related to breast-feeding intention,
initiation, duration, and weaning among women who quit smoking as a result of
pregnancy may inform interventions to increase breast-feeding rates among women
who smoke. Methods: Women (N = 300) who quit smoking as a result of pregnancy and
enrolled in a postpartum relapse prevention trial were interviewed about breast
feeding intention prior to delivery. Breast-feeding initiation, duration, reasons
for weaning, and relapse to smoking were assessed at 12-weeks postpartum.
Results: The majority of pregnant former smokers intended to breastfeed (68%),
and actual rates of breast feeding were higher (74%). Among women who initiated
breast feeding, weaning before 2 months was common (41%). For most women (69%),
smoking had no effect on breast-feeding decisions. Among the 31% of women who
reported that smoking influenced their feeding decisions, 83% indicated that they
did not smoke or decreased smoking frequency in order to breastfeed while 17% did
not breastfeed or quit breast feeding in order to smoke. Women who decided to
forgo breast feeding to smoke were significantly more likely to have a high
school education or less (p < .001) and to be African American (p < .0001) than
those who had other reasons not to breastfeed. Conclusions: Most women who quit
smoking during pregnancy initiate breast feeding, and the majority report smoking
did not influence feeding decisions. Importantly, among women for whom smoking
did influence feeding decisions, most reported changing smoking behavior to
enable breast feeding. Interventions to increase breast-feeding initiation and
duration may decrease postpartum relapse and improve maternal and infant health.
Implications: This study extends the literature on women's perception of the
influence of smoking on breast feeding by assessing breast-feeding intent,
initiation, duration, and reasons for weaning longitudinally among women who quit
smoking as a result of pregnancy. The results support a need for additional
research to determine the effectiveness of breast feeding supports as a component
of interventions to reduce postpartum smoking relapse.
PMID- 28403460
TI - Factors Associated With Quitting Among Smoking Pregnant Women From Small Town and
Rural Areas in Poland.
AB - Introduction: Smoking rates among women in Poland are high, and access to
specialized smoking cessation services in rural areas are limited. The aim of
this study was to assess factors related to quitting among pregnant women who
smoke in rural areas of Poland. Methods: Data were collected during interviews
conducted by midwives among 4512 women at various stages of their pregnancy. The
interviews took place in small towns with populations having less than 8000
residents, located within 12 out of 16 voivodships (provinces). We used exhaled
carbon monoxide to verify self-reported smoking status. Results: Overall, 38% of
women interviewed (n = 1578) smoked before they found out they were pregnant.
Among these women, 33% quit just after they had become aware of their pregnancy.
The main predictors of early quitting were: higher educational attainment among
pregnant women (adjusted odds ratio [AOR] 3.21; 95% confidence interval [CI] =
1.81-5.68), secondary educational attainment among their partners (AOR 1.63; 95%
CI = 1.06-2.48), and not having children (AOR 1.71; 95% CI = 1.31-2.24). The main
barriers to early quitting were: living with at least one current smoker (AOR
0.55, 95% CI = 0.39-0.76), being single (AOR 0.45; 95% CI = 0.29-0.71), and
having both parents smoke cigarettes (AOR 0.67; 95% CI = 0.46-0.97). Conclusions:
A modest proportion of women included in this study quit after they became aware
of their pregnancy. However, women faced multiple barriers to quitting, including
the smoking status of their family members. The factors identified in the study
can inform the design of tailored interventions for pregnant women in rural
areas. Implications: Smoking rates among women in Poland are high, and access to
specialized smoking cessation services in rural areas are limited. This study
found that women were motivated to quit smoking, and many quit after they had
become aware of their pregnancy. However, women faced multiple barriers to
quitting, including the smoking status of their family members. The factors
identified in the study can inform the design of tailored interventions for
pregnant women in rural areas.
PMID- 28403461
TI - Toward Enhancing Treatment for Pregnant Smokers: Laying the Groundwork for the
Use of Complementary and Alternative Medicine Approaches.
AB - Introduction: Although effective treatments exist, most women who smoke during
pregnancy neither seek nor receive treatment. Complementary and alternative
medicine (CAM) treatments (eg, mindfulness, yoga, and acupuncture) may be
attractive, low-cost options that can be used to assist a large proportion of
pregnant women with smoking cessation. Methods: This study examined participant
characteristics and treatment utilization among pregnant smokers in the National
Survey on Drug Use and Health (NSDUH) and the National Health Interview Survey
(NHIS) in order to explore the prevalence and predictors of CAM use for any
purpose within this population. Results: Results indicated that a considerable
proportion (6.9%-29.1%) of pregnant smokers are already accessing CAM,
particularly Whites and those of greater socioeconomic status. Use of yoga,
meditation, and massage increased across study waves. NSDUH participants were
most likely to report seeking chiropractic or massage therapy; NHIS participants
most frequently reported use of herbs/supplements, deep breathing, and
meditation. Conclusions: Up to roughly a quarter of women endorsed
traditional/conventional and CAM treatment use, suggesting that some pregnant
smokers are open to trying a variety of approaches to promote health. Further
research is needed to validate CAM treatments for smoking cessation and to guide
safety and treatment recommendations during pregnancy. Implications: CAM
treatments may be an attractive treatment alternative for pregnant smokers.
However, no previous investigations have examined whether pregnant smokers seek
out these treatments. Using nationally representative survey data, the present
study aimed to explore whether pregnant smokers use CAM treatments. We found that
approximately 7%-29% of pregnant smokers reported using a variety of CAM methods,
suggesting the need for further investigation into the efficacy and dissemination
of CAM for smoking in pregnancy.
PMID- 28403462
TI - Medicaid Coverage of Smoking Cessation Counseling and Medication Is Underutilized
for Pregnant Women.
AB - Introduction: Policies to promote smoking cessation among Medicaid-insured
pregnant women have the potential to assist a significant proportion of pregnant
smokers. In 2010, Kansas Medicaid began covering smoking cessation counseling for
pregnant smokers. Our aim was to evaluate the use of smoking cessation benefits
provided to pregnant women as a result of the Kansas Medicaid policy change that
provided reimbursement for physician-provided smoking cessation counseling.
Methods: We examined Kansas Medicaid claims data to estimate rates of delivery of
smoking cessation treatment to Medicaid-insured pregnant women in Kansas from
fiscal year 2010 through 2013. We analyzed the number of pregnant women who
received physician-provided smoking cessation counseling indicated by procedure
billing codes (ie, G0436 and G0437) and medication (ie, nicotine replacement
therapy, bupropion, or varenicline) located in outpatient managed care encounter
and fee-for-service claims data. We estimated the number of Medicaid-insured
pregnant smokers using the national smoking prevalence (14%) in this population
and the number of live births reported in Kansas. Results: Annually from 2010 to
2013, approximately 27.2%-31.6% of pregnant smokers had claims for nicotine
replacement therapy, bupropion, or varenicline. Excluding claims for bupropion, a
medication commonly prescribed to treat depression, claims ranged from 9.3% to
11.1%. Following implementation of Medicaid coverage for smoking cessation
counseling, less than 1% of estimated smokers had claims for counseling.
Conclusions: This low claims rate suggests that simply changing policy is not
sufficient to ensure use of newly implemented benefits, and that there probably
remain critical gaps in smoking cessation treatment. Implications: This study
evaluates the use of Medicaid reimbursement for smoking cessation counseling
among low-income pregnant women in Kansas. We describe the Medicaid claims rates
of physician-provided smoking cessation counseling for pregnant women, an
evidence-based and universally recommended treatment approach for smoking
cessation in this population. Our findings show that claims rates for smoking
cessation benefits in this population are very low, even after policy changes to
support provision of cessation assistance were implemented. Additional studies
are needed to determine whether reimbursement is functioning as intended and
identify potential gaps between policy and implementation of evidence-based
smoking cessation treatment.
PMID- 28403463
TI - Facilitators and Barriers to Cigarette Smoking While Pregnant for Women With
Substance Use Disorders.
AB - Introduction: Cigarette smoking among pregnant women diagnosed with substance use
disorders (SUD) is four times higher than smoking among pregnant women without
SUD. However, much of the literature on pregnancy and smoking has centered on the
latter group. This study used the Health Belief Model as a framework to explore
smoking cessation in pregnant women with SUD. Methods: Four 60-minute focus
groups were conducted with a semistructured moderator guide. Participants (N =
21) were women who smoked during pregnancy, gave birth within the past year, and
were residing at a women's SUD treatment center. A directed content analysis
approach was utilized for examining focus group data. Results: Similar to women
without SUD, barriers to smoking cessation were smoking behaviors of partners and
using cigarettes to cope with stress; reasons to stop included the child's
health. Participants reported that having children gave them a sense of purpose
and their guilt about smoking became stronger once the child was born. Smoking
also provided them with a sense of freedom. Women's triggers for smoking were
interconnected with those of other addictive substances. Women identified
behaviors that helped and hindered them. Conclusions: Lack of internalization of
the negative effects of smoking was a barrier to stopping, indicating a need for
health literacy. Furthermore, women struggled with the perception of tobacco as a
drug as compared with other addictive substances. Exploring facilitators and
barriers to smoking cessation among pregnant women with SUD is critical to the
health and well-being of this vulnerable population. Implications: This study
adds to the literature by identifying childbirth as an opportunity to address
smoking for women with SUD. Furthermore, it supports the interconnectedness of
triggers for smoking with those of other addictive substances, and the perceptual
barrier tobacco is often not viewed as a drug by women with SUD. Findings
demonstrate a need for increased health literacy and enhanced external supports
around smoking cessation for this population.
PMID- 28403464
TI - Supporting Aboriginal Women to Quit Smoking: Antenatal and Postnatal Care
Providers' Confidence, Attitudes, and Practices.
AB - Introduction: Tobacco use during pregnancy is substantially higher among
Aboriginal women compared to non-Aboriginal women in Australia. However, no
studies have investigated the amount or type of smoking cessation care that staff
from Aboriginal antenatal and postnatal services provide to clients who smoke or
staff confidence to do so. This study examined Aboriginal antenatal and postnatal
staff confidence, perceived role and delivery of smoking cessation care to
Aboriginal women and characteristics associated with provision of such care.
Methods: Staff from 11 Aboriginal Maternal and Infant Health Services and eight
Aboriginal Child and Family Health services in the Hunter New England Local
Health District in Australia completed a cross-sectional self-reported survey (n
= 67, response rate = 97.1%). Results: Most staff reported they assessed clients'
smoking status most or all of the time (92.2%). However, only a minority reported
they offered a quitline referral (42.2%), provided follow-up support (28.6%) or
provided nicotine replacement therapy (4.7%) to most or all clients who smoked.
Few staff felt confident in motivating clients to quit smoking (19.7%) and
advising clients about using nicotine replacement therapy (15.6%). Staff
confident with talking to clients about how smoking affected their health had
significantly higher odds of offering a quitline referral [OR = 4.9 (1.7-14.5)]
and quitting assistance [OR = 3.9 (1.3-11.6)] to clients who smoke. Conclusions:
Antenatal and postnatal staff delivery of smoking cessation care to pregnant
Aboriginal women or mothers with young Aboriginal children could be improved.
Programs that support Aboriginal antenatal and postnatal providers to deliver
smoking cessation care to clients are needed. Implications: Aboriginal antenatal
and postnatal service staff have multiple opportunities to assist Aboriginal
women to quit smoking during pregnancy and postpartum. However, staff confidence
and practices of offering various forms of smoking cessation support to pregnant
Aboriginal women is unexplored. This is the first study to examine the amount and
type of smoking cessation support Aboriginal antenatal and postnatal service
staff provide to Aboriginal women, staff confidence and their perceived role in
delivering smoking cessation care. This information is valuable for developing
strategies that assist antenatal and postnatal staff to improve their delivery of
smoking cessation care to Aboriginal women.
PMID- 28403465
TI - Smoking in Pregnancy Among Indigenous Women in High-Income Countries: A Narrative
Review.
AB - Introduction: Pregnant women in socioeconomically disadvantaged circumstances,
such as Indigenous women, have a high prevalence of smoking. Tobacco smoking is
the most significant reversible risk factor for the health of Indigenous pregnant
women and their babies. Methods: As researchers working in this specialized area,
we conducted a narrative review of the literature on smoking among Indigenous
pregnant women in the United States, Canada, New Zealand, and Australia. We
summarize prevalence and factors influencing tobacco use, interventions, and
evidence gaps for tobacco control and smoking cessation. Recommendations are made
for future interventions, policy changes, and much-needed research. Results:
Common themes emerging across the four countries reveal opportunities for cross
cultural collaborative studies and trials. These include the social-normative use
of tobacco as barriers to quitting in pregnancy and the need for evaluations of
interventions at the family and community level. Socioeconomic disparities
underscore the importance of enhancing the implementation and reach of strategies
to prevent and reduce prenatal tobacco smoking among Indigenous women. Elders and
community health care providers as role models for nontobacco use could be
explored. Qualitative work is needed to understand the barriers and
opportunities, such as cultural strengths supporting quitting tobacco to develop
more effective approaches. Conclusions: Although a high-priority group, there
remains a dearth of research on Indigenous women's smoking in pregnancy. Studies
have assessed knowledge and attitudes to smoking in pregnancy, and small
feasibility studies and a few empirical trials have been conducted.
Recommendations for promising culturally appropriate cessation interventions have
been made. Larger trials are warranted. Implications: Strategies to support
quitting among pregnant Indigenous women need to be multifactorial and take
account of the social determinants of smoking including historical antecedents,
community norms, cultural strengths, and recognition of individual and community
needs. Cross-country research collaborations have the potential to leverage
funding, share expertise, and strengthen approaches to tackle an important and
poorly attended health disparity that has a profound impact on the entire life
course for Indigenous peoples.
PMID- 28403467
TI - Development of Social and Demographic Differences in Maternal Smoking Between
1999 and 2014 in Norway.
AB - Introduction: The Medical Birth Registry of Norway provides national coverage of
all births in Norway. In this study trends of smoking at the beginning of
pregnancy and the variation of these trends across different sociodemographic
groups are analyzed. This knowledge is important for planning interventions both
in the general population and specifically among pregnant women. Methods: All
births registered in Medical Birth Registry of Norway 1999-2014 with information
on mothers' smoking status were included in the overall analyses of the smoking
trends (806 298). Records from 210 268 births in two time periods 1999-2000 and
2013-2014 were selected, and for the multivariate analyses we used general linear
models to provide adjusted risk ratios. Results: The prevalence of maternal
smoking at the beginning of pregnancy decreased from 25% to 8% over the 15-year
period. Mothers with low, medium, and high education, respectively, had a 46% (RR
0.54, CI 0.52-0.55), 62% (RR 0.38, CI 0.37-0.40), and 80% (RR 0.20, CI 0.19-0.22)
reduction in maternal smoking between the two time periods. Similarly, the
decline in smoking was greater for mothers who were married or living together
(64%; RR 0.36, CI 0.35-0.37) than for single mothers (39%; RR 0.61, CI 0.58
0.64). Immigrants had a lower smoking prevalence than Norwegians in the entire
period 1999-2014. Conclusion: The prevalence of smoking during pregnancy in
Norway decreased in all population groups, but the relative differences between
the educational groups increased from 1999-2000 to 2013-2014. This is a public
health concern and a strong contributor to health disparities. Implications:
Women with low and medium education level and single mothers had the highest
smoking prevalence and the lowest decline over the two time periods. These groups
constitute 45% of our study population, the relatively high maternal smoking in
these groups continues to be of public health concern for maternal and child
health.
PMID- 28403466
TI - The Role of Maternal Adverse Childhood Experiences and Race in Intergenerational
High-Risk Smoking Behaviors.
AB - Introduction: A history of adversity in childhood is associated with cigarette
smoking in adulthood, but there is less evidence for prenatal and next-generation
offspring smoking. We investigated the association between maternal history of
childhood adversity, pregnancy smoking, and early initiation of smoking in
offspring, overall and by maternal race/ethnicity. Methods: Data on maternal
childhood exposure to physical abuse, household alcohol abuse, and household
mental illness, prenatal smoking behaviors, and offspring age of smoking
initiation were analyzed from the US National Longitudinal Survey of Youth 1979
(NLSY79, n = 2999 mothers) and the NLSY79 Children and Young Adults Survey
(NLSYCYA, n = 6596 children). Adjusted risk ratios were estimated using log
linear regression models. We assessed multiplicative interaction by
race/ethnicity for all associations and a three-way interaction by maternal
exposure to adversity and race/ethnicity for the association between prenatal and
child smoking. Results: Maternal exposure to childhood physical abuse was
significantly associated with 39% and 20% increased risks of prenatal smoking and
child smoking, respectively. Household alcohol abuse was associated with
significantly increased risks of 20% for prenatal smoking and 17% for child
smoking. The prenatal smoking-child smoking relationship was modified by maternal
exposure to household alcohol abuse and race. There were increased risks for
Hispanic and white/other mothers as compared to the lowest risk group: black
mothers who did not experience childhood household alcohol abuse. Conclusions:
Mothers in this national sample who experienced adversity in childhood are more
likely to smoke during pregnancy and their offspring are more likely to initiate
smoking before age 18. Findings varied by type of adversity and race/ethnicity.
Implications: These findings support the importance of a life-course approach to
understanding prenatal and intergenerational smoking, and suggest that maternal
early-life history is a potentially important risk factor that could be targeted
with screening and interventions to reduce smoking in pregnant women and their
children.
PMID- 28403468
TI - Serious Psychological Distress and Smoking During Pregnancy in the United States:
2008-2014.
AB - Introduction: The current study examined the relationship between acute (past 30
day) and recent (past year but not past 30 day) serious psychological distress
(SPD) and smoking during pregnancy among women in the United States overall,
stratified by demographic characteristics, and described the change in the
prevalence of prenatal smoking among women with and without SPD, from 2008 to
2014. Methods: Data were drawn from the National Survey on Drug Use and Health
(NSDUH), an annual cross-sectional study of US persons aged 12 and over. SPD and
smoking in the past 30 days among pregnant women, aged 18 and older, were
examined using logistic regression models. Heterogeneity in this association by
demographic characteristics, trends over time, and level of cigarette consumption
was also examined. Results: Prenatal smoking was common. Almost 40% of pregnant
women with acute SPD reported smoking, 23% of pregnant women with recent SPD
smoked, and 11.7% of pregnant women without recent SPD smoked. No significant
change was found in the prevalence of prenatal smoking from 2008 to 2014 in any
of these groups. Robust relationships were found between acute (OR = 5.05 [3.64
6.99]) and recent SPD (OR = 2.37 [1.74-3.24]) and smoking; these findings
remained after adjusting for demographics. Conclusions: SPD and smoking during
pregnancy are strongly associated; this relationship is present across all
sociodemographic groups and the prevalence of smoking in pregnancy has remained
relatively unchanged over the past decade both in the presence and absence of
SPD. Implications: SPD and smoking in pregnancy are robustly linked; the
prevalence of smoking in pregnancy is extremely high in women with SPD. Screening
women with mental health problems for prenatal smoking, as well as screening
pregnant smokers for mental health problems, seems warranted and may assist more
women in seeking and utilizing treatment options. Efforts to reduce the
prevalence of smoking during pregnancy might specifically target women with SPD,
where the potential for impact is substantial.
PMID- 28403469
TI - Opportunities Missed: A Cross-Sectional Survey of the Provision of Smoking
Cessation Care to Pregnant Women by Australian General Practitioners and
Obstetricians.
AB - Introduction: Similar to other high-income countries, smoking rates in pregnancy
can be high in specific vulnerable groups in Australia. Several clinical
guidelines exist, including the 5A's (Ask, Advice, Assess, Assist, and Arrange),
ABCD (Ask, Brief advice, Cessation, and Discuss), and AAR (Ask, Advice, and
Refer). There is lack of data on provision of smoking cessation care (SCC) of
Australian General Practitioners (GPs) and Obstetricians. Methods: A cross
sectional survey explored the provision of SCC, barriers and enablers using the
Theoretical Domains Framework, and the associations between them. Two samples
were invited: (1) GPs and Obstetricians from a college database (n = 5571); (2)
GPs from a special interest group for Indigenous health (n = 500). Dimension
reduction for the Theoretical Domains Framework was achieved with factor
analysis. Logistic regression was carried out for performing all the 5A's and the
AAR. Results: Performing all of the 5A's, ABCD, and AAR "often and always" was
reported by 19.9%, 15.6%, and 49.2% respectively. "Internal influences" (such as
confidence in counselling) were associated with higher performance of the 5A's
(Adjusted OR 2.69 (95% CI 1.5, 4.8), p < .001), whereas "External influences"
(such as workplace routine) were associated with higher performance of AAR
(Adjusted OR 1.7 (95% CI 1, 2.8), p = .035). Conclusions: Performance in
providing SCC to pregnant women is low among Australian GPs and Obstetricians.
Training clinicians should focus on improving internal influences such as
confidence and optimism. The AAR may be easier to implement, and interventions at
the service level should focus on ensuring easy, effective, and acceptable
referral mechanisms are in place. Implications: Improving provision of the 5A's
approach should focus on the individual level, including better training for GPs
and Obstetricians, designed to improve specific "internal" barriers such as
confidence in counselling and optimism. The AAR may be easier to implement in
view of the higher overall performance of this approach. Interventions on a more
systemic level need to ensure easy, effective, and acceptable referral mechanisms
are in place. More research is needed specifically on the acceptability of the
Quitline for pregnant women, both Indigenous and non-Indigenous.
PMID- 28403470
TI - Perinatal Biochemical Confirmation of Smoking Status by Trimester.
AB - Introduction: Tobacco use during pregnancy is the most modifiable risk factor
associated with poor pregnancy outcomes. Self-reported tobacco use has been
demonstrated to have high misclassification rates. The aims were to examine
misclassification rates of perinatal tobacco use during each trimester of
pregnancy and 8 weeks postpartum, and to evaluate characteristics associated with
misclassification of tobacco use status. Methods: This is secondary analysis of a
prospective, multicenter trial of pregnant women, and it includes participants
who were biochemically identified as tobacco users during their first trimester
(N = 103). Each trimester and once postpartum, tobacco use was assessed via self
report and validated using a cutoff of 100 ng/mL for urine cotinine via NicAlert
test strips to indicate current use. Those who self-reported as nonusers but were
identified as users via urine cotinine were considered misclassified;
misclassification rates were determined for each time period. Logistic regression
assessed maternal factors associated with misclassification status. Results:
Misclassification rates declined from 35.0% at first trimester to 31.9% and 26.6%
at the second and third; the postpartum rate was 30.4%. These rates did not
differ significantly from each other at the 0.05 level. Race/ethnicity was
associated with misclassification status; white/non-Hispanic women were 87% less
likely to be misclassified (p < .001). Conclusion: Misclassification of prenatal
smoking status decreases as pregnancy progresses, though the observed rate change
was not significant. Minority women may be at particular risk for non-disclosure
of tobacco use. Biochemical validation should be considered when assessing
perinatal tobacco use via self-report, given high misclassification rates
throughout the perinatal period. Implications: These results demonstrate that
regardless of trimester, more than one-quarter of tobacco-using pregnant women
may not disclose tobacco use throughout pregnancy and early postpartum. Although
the rate of misclassification decreased from first to third trimester and then
increased in the immediate postpartum, these changes in misclassification rates
were not significant. Minority groups may be at particular risk of
misclassification compared with white/non-Hispanic women. Biochemical validation
is warranted throughout pregnancy to encourage cessation as tobacco use is one of
the most easily-modified risk factors for poor birth outcomes.
PMID- 28403471
TI - Do Psychiatric Disorders or Measures of Distress Moderate Response to Postpartum
Relapse Prevention Interventions?
AB - Introduction: Most women who quit smoking during pregnancy will relapse
postpartum. Interventions for sustained postpartum abstinence can benefit from
understanding prenatal characteristics associated with treatment response. Given
that individuals with psychiatric disorders or elevated depressive symptoms have
difficulty quitting smoking and that increases in depressive symptoms prenatally
are common, we examined the relevance of psychiatric diagnoses, prenatal
depressive symptoms, and stress to postpartum relapse prevention intervention
response. Methods: Pregnant women (N = 300) who quit smoking during pregnancy
received intervention (with specialized focus on mood, weight, and stress
[STARTS] or a comparison [SUPPORT]) to prevent postpartum relapse. As previously
published, nearly one-third and one-quarter of women achieved biochemically
confirmed sustained abstinence at 24- and 52-weeks postpartum, with no difference
in abstinence rates between the interventions. Women completed psychiatric
interviews and questionnaires during pregnancy. Smoking was assessed in
pregnancy, and 24- and 52-weeks postpartum. Results: Psychiatric disorders did
not predict sustained abstinence or treatment response. However, treatment
response was moderated by end-of-pregnancy depressive symptoms (chi2 = 9.98, p =
.002) and stress (chi2 = 6.90, p = .01) at 24- and 52-weeks postpartum and
remained significant after including covariates. Women with low distress achieved
higher abstinence rates in SUPPORT than in STARTS (37% vs. 19% for depressive
symptoms; 36% vs. 19% for stress), with no difference for women with high
symptoms. Conclusions: Prenatal depressive symptoms and stress predicted
differential treatment efficacy in women with low symptoms, not in women with
high symptoms. Diagnostic history did not predict treatment differences. Future
research to address prenatal distress may help tailor postpartum relapse
prevention interventions. Implications: We examined prenatal history of
psychiatric disorders and psychiatric distress as moderators of response to
postpartum smoking relapse prevention intervention that either included or did
not include added content on mood, stress, and weight concerns. For women with
lower psychiatric distress, the added focus is not necessary, as these women
achieved greater sustained abstinence in the less-intensive treatment.
Understanding which women need which level of care to sustain abstinence can help
allocate resources for all postpartum former smokers. These findings underscore
the importance of perinatal symptom monitoring and promoting behavioral health
more broadly in pregnant and postpartum women.
PMID- 28403472
TI - Smoking Cessation for Pregnant Smokers: Development and Pilot Test of an Emotion
Regulation Treatment Supplement to Standard Smoking Cessation for Negative Affect
Smokers.
AB - Introduction: Negative affect has been identified as a factor influencing
continued smoking during pregnancy. In this study, a multi-component emotion
regulation intervention was developed to address negative emotional smoking
triggers and pilot-tested among low-income pregnant smokers. Treatment
feasibility and acceptability, cotinine-verified rates of smoking cessation, and
self-report of mean cigarettes smoked were assessed. Methods: Pregnant smokers
who self-reported smoking in response to negative affect (N = 70) were randomly
assigned to receive one of two 8-session interventions: (1) emotion regulation
treatment combined with standard cognitive-behavioral smoking cessation (ERT +
CBT) or (2) a health and lifestyle plus standard smoking cessation active control
(HLS + CBT). Outcomes for the 4-month period following the quit date are
reported. Results: Treatment attendance and subjective ratings provide evidence
for the feasibility and acceptability of the ERT + CBT intervention. Compared
with the HLS + CBT control condition, the ERT + CBT condition demonstrated higher
abstinence rates at 2 months (ERT + CBT = 23% vs. HLS + CBT = 0%, OR = 13.51; 95%
CI = 0.70-261.59) and 4 months (ERT = 18% vs. HLS = 5%; OR = 2.98; 95% CI = 0.39
22.72) post-quit. Mean number of cigarettes per day was significantly lower in
ERT + CBT at 2 months (ERT + CBT = 2.73 (3.35) vs. HLS + CBT = 5.84 (6.24); p =
.05) but not at 4 months (ERT + CBT = 2.15 (3.17) vs. HLS + CBT = 5.18 (2.88); p
= .06) post-quit. Conclusions: The development and initial test of the ERT + CBT
intervention supports its feasibility and acceptability in this difficult-to
treat population. Further development and testing in a Stage II randomized
clinical trial are warranted. Implications: Negative affect has been identified
as a motivator for continued smoking during pregnancy. To date, smoking cessation
interventions for pregnant smokers have not specifically addressed the role of
negative affect as a smoking trigger. This treatment development pilot study
provides support for the feasibility and acceptability of a multi-component ERT +
CBT for low-income pregnant smokers who self-report smoking in response to
negative affect. Study findings support further testing in a fully-powered Stage
II efficacy trial powered to assess mediators and moderators of treatment
effects.
PMID- 28403473
TI - Maternal Smoking During Pregnancy and the Risk of Psychiatric Morbidity in
Singleton Sibling Pairs.
AB - Introduction: Maternal smoking during pregnancy has been associated with an
increased risk for psychiatric morbidity. We further studied this with Finnish
siblings to control for genetic/familial factors. Methods: From the Finnish
Medical Birth Register, sibling pairs were selected as the first two children
born 1987-1995 to the same mother (n = 150 168 pairs), along with information on
maternal smoking (no smoking/smoking). Information on the children's psychiatric
diagnoses related to outpatient care visits (1998-2013) and inpatient care (1987
2013), and the mothers' psychiatric morbidity (1969-2013) was derived from the
Finnish Hospital Discharge Register. The first pair analysis compared siblings of
mothers who only smoked in the first pregnancy (Quitters, 4.7%) and mothers who
smoked in both pregnancies (Smokers, 9.6%); the second analysis included mothers
who smoked only in the second pregnancy (Starters, 3.3%) and mothers who did not
smoke in either pregnancy (Nonsmokers, 77.5%). Smoking information was missing
for 5.0% of pairs. Psychiatric morbidity of the siblings and mother was included
in the statistical analyses. Results: The risk of psychiatric diagnoses was
significantly lower for the second child of quitters (adjusted OR 0.77, 95% CI
0.72-0.83) compared to the risk among smokers. A higher risk for psychiatric
diagnoses was found for the second child of starters (1.39, 1.30-1.49) compared
to the risk among nonsmokers. The effect of smoking was more robust for
externalizing diagnoses. Conclusions: Maternal smoking was independently
associated with a higher risk for psychiatric morbidity in children, even when
controlling thoroughly for genetic and familial factors. Implications: Maternal
smoking during pregnancy has an independent effect on the risk of psychiatric
morbidity in children, even after controlling for non-measurable genetic/familial
factors by using a sibling pair design. The effect of maternal smoking was robust
for externalizing diagnoses. Maternal smoking during pregnancy had an effect on
diagnoses both in outpatient and inpatient care.
PMID- 28403474
TI - Smoking in Pregnancy and Fetal Growth: The Case for More Intensive Assessment.
AB - Introduction: Many studies on prenatal tobacco exposure (PTE) effects have relied
on single item retrospective measures of PTE. However, it is unclear how these
single item measures may relate to more intensive maternal self-reports and to
biological markers of maternal use and/or fetal exposure. It is also unclear
whether these measures may be more valid predictors of fetal growth (gestational
age, birthweight, head circumference, and birth length). Methods: Data were
obtained from 258 women during their pregnancy. PTE was assessed by four methods:
a single item question, a calendar-based self-report measure from each trimester
of pregnancy, maternal salivary cotinine assays, and nicotine and metabolites in
infant meconium. We hypothesized that the more intensive measures and biological
assays would account for additional variance in birth outcomes, above and beyond
the single item measure. Results: The single item self-report measure was not
related to fetal growth. However, the more intensive calendar based self-report
measure and the biological assays of PTE (ie, maternal salivary assays and infant
meconium) were significant predictors of poor fetal growth, even with the single
item measure in the model. Conclusions: The negative effects of PTE on important
child outcomes may be greatly underestimated in the literature as many studies
use single item self-report measures to ascertain PTE. Whereas more intensive
self-report measures or biological assays may be cost prohibitive in large scale
epidemiological studies, using a combination of measures when possible should be
considered given their superiority both identifying prenatal smokers and
predicting poor fetal growth. Implications: The present work underscores the
importance of measurement issues when assessing associations between PTE and
fetal growth. Results suggest that we may be greatly underestimating the negative
effects of prenatal smoking on fetal growth and other important child outcomes if
we rely solely on restricted single item self-report measures of prenatal
smoking. Researchers should consider more intensive prospective self-report
measures and biological assays as viable and superior alternatives to single item
self-report measures.
PMID- 28403476
TI - Smoking in Pregnancy: An Ongoing Challenge.
PMID- 28403475
TI - Cigarette Smoking During Pregnancy: Do Complete Abstinence and Low Level
Cigarette Smoking Have Similar Impact on Birth Weight?
AB - Objectives: Despite awareness of negative health outcomes associated with
smoking, pregnant smokers might reduce their tobacco consumption thinking that a
low smoking rate reduces smoking-related negative birth outcomes. We aimed to
assess in a clinical sample whether there is a smoking rate that would not impact
on birth weight (BW). Methods: Pregnant smokers >=18 years, gestational age of 9
20 weeks of amenorrhea, motivated to quit smoking, smoking >=5 cigarettes/day
(cpd) and their newborns (381 singleton, live births) were included in this
secondary analysis of a French smoking cessation trial. Results: The mean BW when
the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd,
3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking
>=10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged
from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when
the mother quit. In the multivariable analysis, adjusted for all significant
confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228
g; when smoking 5-9 cpd, 251 g; and when smoking >=10 cpd, 262 g (all p <= .02)
compared to newborns' BW of mothers who stopped smoking since quit date.
Conclusions: Even low cigarette consumption during pregnancy is associated with
BW loss. All efforts should be made to help pregnant smokers quit completely
during their pregnancy. Implications: As an alternative to quitting smoking,
pregnant smokers reduce their smoking rate thinking that this diminishes smoking
related negative health outcomes. No study has established whether low smoking
rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to
abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns
of mothers who smoked even less than 5 cpd was significantly lower than of those
whose mothers quit; effect sizes of different consumption levels on BW ranged
from moderate (>0<5 cpd) to large (>=10 cpd). Even low smoking rate is associated
with reduced BW compared to complete maternal smoking abstinence.
PMID- 28403477
TI - Risk Stratification for Surgical Site Infections in Colon Cancer.
AB - Importance: Surgical site infections (SSIs) feature prominently in surgical
quality improvement and pay-for-performance measures. Multiple approaches are
used to prevent or reduce SSIs, prompted by the heavy toll they take on patients
and health care budgets. Surgery for colon cancer is not an exception. Objective:
To identify a risk stratification score based on baseline and operative
characteristics. Design, Setting, and Participants: This retrospective cohort
study included all patients treated surgically for colon cancer at Massachusetts
General Hospital from 2004 through 2014 (n = 1481). Main Outcomes and Measures:
The incidence of SSI stratified over baseline and perioperative factors was
compared and compounded in a risk score. Results: Among the 1481 participants, 90
(6.1%) had SSI. Median (IQR) age was 66.9 (55.9-78.1) years. Surgical site
infection rates were significantly higher among people who smoked (7.4% vs 4.8%;
P = .04), people who abused alcohol (10.6% vs 5.7%; P = .04), people with type 2
diabetics (8.8% vs 5.5%; P = .046), and obese patients (11.7% vs 4.0%; P < .001).
Surgical site infection rates were also higher among patients with an operation
duration longer than 140 minutes (7.5% vs 5.0%; P = .05) and in nonlaparoscopic
approaches (clinically significant only, 6.7% vs 4.1%; P = .07). These risk
factors were also associated with an increase in SSI rates as a compounded score
(P < .001). Patients with 1 or fewer risk factors (n = 427) had an SSI rate of
2.3%, equivalent to a relative risk of 0.4 (95% CI, 0.16-0.57; P < .001);
patients with 2 risk factors (n = 445) had a 5.2% SSI rate (relative risk, 0.78;
95% CI, 0.49-1.22; P = .27); patients with 3 factors (n = 384) had a 7.8% SSI
rate (relative risk, 1.38; 95% CI, 0.91-2.11; P = .13); and patients with 4 or
more risk factors (n = 198) had a 13.6% SSI rate (relative risk, 2.71; 95% CI,
1.77-4.12; P < .001). Conclusions and Relevance: This SSI risk assessment factor
provides a simple tool using readily available characteristics to stratify
patients by SSI risk and identify patients at risk during their postoperative
admission. Thereby, it can be used to potentially focus frequent monitoring and
more aggressive preventive efforts on high-risk patients.
PMID- 28403478
TI - Non-animal approaches for toxicokinetics in risk evaluations of food chemicals.
AB - The objective of the present work was to review the availability and predictive
value of non-animal toxicokinetic approaches and to evaluate their current use in
European risk evaluations of food contaminants, additives and food contact
materials, as well as pesticides and medicines. Results revealed little use of
quantitative animal or human kinetic data in risk evaluations of food chemicals,
compared with pesticides and medicines. Risk evaluations of medicines provided
sufficient in vivo kinetic data from different species to evaluate the predictive
value of animal kinetic data for humans. These data showed a relatively poor
correlation between the in vivo bioavailability in rats and dogs versus that in
humans. In contrast, in vitro (human) kinetic data have been demonstrated to
provide adequate predictions of the fate of compounds in humans, using
appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data
with in silico kinetic modelling. Even though in vitro kinetic data were found to
be occasionally included within risk evaluations of food chemicals, particularly
results from Caco-2 absorption experiments and in vitro data on gut-microbial
conversions, only minor use of in vitro methods for metabolism and quantitative
in vitro-in vivo extrapolation methods was identified. Yet, such quantitative
predictions are essential in the development of alternatives to animal testing as
well as to increase human relevance of toxicological risk evaluations. Future
research should aim at further improving and validating quantitative alternative
methods for kinetics, thereby increasing regulatory acceptance of non-animal
kinetic data.
PMID- 28403479
TI - Adaptation of the KeratinoSensTM skin sensitization test to animal-product-free
cell culture
AB - Skin sensitization is the process by which a substance induces an allergic
reaction following skin contact. The process has been described as an adverse
outcome pathway (AOP), including several key events, from skin penetration and
covalent protein binding, to keratinocyte activation, dendritic cell activation
and T-lymphocyte proliferation. The in vitro assay KeratinoSensTM measures the
activation of keratinocytes. It is fully accepted at a regulatory level (OECD TG
442d) and complies with a range of legislation including the EU Cosmetics
Regulation, REACH, and the CLP Regulation. Currently, many in vitro methods use
animal-derived components in their cell culture systems. Many stakeholders in the
cosmetics industry have both scientific and ethical concerns relating to this
issue and have stated a strong preference for fully human in vitro test systems.
We have adapted the KeratinoSensTM method to animal product-free condi-tions, and
carried out an in-house validation with 21 reference substances, including those
listed in the Performance Standards associated with OECD TG442d. The modified
method was shown to be equivalent to the Validated Ref-erence Method (VRM), with
comparable values for accuracy (85.7%), sensitivity (84.6%) and specificity
(87.5%), and all acceptance criteria being met. In Europe, data generated by the
adapted method may be used in REACH submissions, and we are now seeking approval
to list the adaptation in OECD TG 442d, enabling formal compliance with a range
of global regulations.
PMID- 28403480
TI - Box Lesion with Single Radiofrequency Clamp.
AB - We introduce a maneuver to perform the box lesion as a part of Cox maze IV
procedure with single radiofrequency clamp. The maneuver entails engaging the
right pulmonary veins with the clamp, then advancing the clamp jaws underneath
the superior vena cava through the transverse sinus to include the roof and the
left pulmonary veins in the clamp. We regularly use this technique for box lesion
with desirable transmurality.
PMID- 28403482
TI - ?
PMID- 28403481
TI - Do Flow and Pulsatility Index within the Accepted Ranges Predict Long-Term
Outcomes after Coronary Artery Bypass Grafting?
AB - Background Transit-time flow measurement (TTFM) is the gold standard for
intraoperative detection of graft failure. Several reports show that TTFM and
distal coronary bed quality (DCBQ) may also be useful for midterm detection of
graft failure. Nonetheless, there are no data regarding their predictive role on
long-term outcomes. Methods Patients with three-vessel disease who underwent
isolated coronary artery bypass grafting (CABG) in 2006 and received at least one
graft to the left anterior descending artery (LAD) or to the first obtuse
marginal (OM1) or posterior descending artery (PDA) were included. Baseline
characteristics, mean graft flow, pulsatility index, and subjective impression of
DCBQ for each coronary territory were collected. Long-term cardiovascular (CV)
and overall survival, operative mortality, and new percutaneous coronary
intervention (PCI) were evaluated. Results A total of 177 patients underwent
isolated CABG. The OM1 was grafted in 131 patients, the LAD in 169 patients, and
the PDA in 100 patients. Neither DQCB nor TTFM were predictors for new PCI.
Independent predictors for overall survival were age, previous acute myocardial
infarction (AMI), and DQCB of OM1 (odds ratio [OR] = 2.97; 95% confidence
interval [CI]: 1.15-7.71). Age, previous AMI, and DCBQ of OM1 (OR = 2.5; 95% CI:
1.39-4.81) were independent predictors for CV survival. Conclusions TTFM on
patients with functioning grafts does not predict long-term survival or
performance of new PCI. Subjective evaluation of distal coronary bed, especially
of the OM1, has a strong impact on long-term outcomes.
PMID- 28403483
TI - ?
PMID- 28403484
TI - ?
PMID- 28403485
TI - ?
PMID- 28403486
TI - ?
PMID- 28403487
TI - ?
PMID- 28403488
TI - ?
PMID- 28403489
TI - ?
PMID- 28403490
TI - ?
PMID- 28403491
TI - ?
PMID- 28403492
TI - [Surgical Management of Acute Scrotum].
AB - Acute scrotum is a challenging emergency situation in children, adolescents and
adults with a variety of underlying conditions and causes. In cases with a
clinical suspicion of torsion of the spermatic cord, immediate surgical
exploration is mandatory. This article details the surgical management of this
condition. Any delay in restoring testicular blood supply may cause irreversible
loss of vital testicular tissue.
PMID- 28403493
TI - [Acute Idiopathic Scrotal Oedema - Differential Diagnosis of the Acute Scrotum].
AB - Acute idiopathic scrotal edema (AISE) is regarded as a rare cause of scrotal
pain, swelling and erythema. Testicular torsion, torsion of the appendage,
epididymitis, hernia and hydrocele are the most common causes of acute scrotum.
The clinical symptoms of AISE are usually mild and the characteristic Doppler
sonography findings make it a valuable differential diagnosis, which can help to
avoid unnecessary exploration.
PMID- 28403494
TI - [Macrohaematuria in Children].
AB - Urethritis posterior is a possible cause of asymptomatic haematuria in
prepubescent boys. It is a benign lesion of the posterior urethra and its
cardinal symptoms are blood spots in the underwear without any laboratory or
radiologic findings. Urethrocystoscopy is the only way to confirm the diagnosis,
but has been subject to criticism as it is associated with a high risk of
strictures. It is advisable to adopt a "wait and see" strategy because urethritis
posterior usually heals spontaneously over time. This condition is most likely
caused by detrusor-sphincter dyssynergia, since behavioural intervention with
biofeedback therapy offers good treatment results.
PMID- 28403495
TI - [Diagnosis and Therapeutic Management in Kidney, Ureter and Bladder Trauma].
AB - Trauma refers to the destruction of tissues or organs by external forces and it
is the most common cause of mortality and morbidity in children (1, 2). Injuries
of the genitourinary tract may be the result of blunt (falls, sport injuries,
motor vehicle accidents and sexual abuse) or penetrating (stab wounds, gun shots,
falling onto sharp objects) injuries. The genitourinary tract is significantly
injured in 2.9% of paediatric trauma patients 4.In the paediatric population, the
kidney is the most affected organ in the genitourinary tract (>60% of all
genitourinary tract injuries) 4. Blunt renal trauma is the most common type of
injury representing 80-90% 4. The paediatric kidney is more susceptible due to
less abdominal and retroperitoneal fat, weaker trunk and abdominal muscles and a
lower position in the abdomen. Preexisting renal abnormalities such as UPJ
obstruction, hydronephrosis, horseshoe kidney or ectopic kidney make the kidney
more vulnerable. Spiral computed tomography is the gold standard method for
radiological assessment. Surgical intervention is needed only in the minority of
children. Isolated ureteral injury due to trauma is very rare in children.
Penetrating ureteral trauma is more common than blunt trauma in the paediatric
population. Among all urological trauma cases, the incidence of ureteral injury
is lower than 1% [4]. Ureteral injuries include contusion, laceration and
avulsion. Because of their hyperextensible vertebral column, children are more
likely to sustain deceleration injuries. Delayed films of IVP and CT are the main
diagnostic tools whereas the gold standard is retrograde ureteropyelography.
Ureteral injury treatment options depend on the location of injury. The bladder
in children is a more abdominal organ than in adults. Lying in an exposed
position above the pelvis, the bladder is more vulnerable in this age group as it
is less well protected due to the less developed abdominal fat and rectus
muscles. Here, too, the most common type of trauma is blunt injury. High
percentages of bladder injuries are associated with pelvic fractures (70-90%) 4.
The average rate of bladder injury in patients with pelvic fractures is 4% in the
paediatric age group 4. Conventional or CT cystography is the gold standard
method of imaging.
PMID- 28403496
TI - [Interdisciplinary Recommendations for the Treatment of Metastatic Renal Cell
Carcinoma].
AB - Thanks to the use of targeted therapies, the prognosis of patients with
metastatic renal cell carcinoma (mRCC) has improved significantly. A median
overall survival of more than 2 years is a realistic claim. These improvements
are also reflected in recent discussions about 3 and more lines of
therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon
alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib
and pazopanib are also approved for second-line therapy, which, for pazopanib, is
confined to the use after cytokine failure. Everolimus (after tyrosine kinase
inhibitor (TKI) treatment), sorafenib (after cytokines) and axitinib (after
treatment with sunitinib or cytokines) are other compounds available for second
line therapy.3 new substances have recently been approved for second-line
therapy: Nivolumab, cabozantinib, and lenvatinib combined with everolimus can be
used after VEGF-targeted treatment has failed. It is for the first time that
targeted immunotherapy and a combination of targeted substances are available for
the treatment of mRCC.There is no new insight as to an optimal sequence therapy.
Study results from a phase III trial suggest that the sequences sorafenib
sunitinib and sunitinib-sorafenib are equally effective.The purpose of an
interdisciplinary expert meeting on RCC was to work out joint treatment
recommendations based on current data and clinical experience and to integrate
them into clinical routine practice. The results are presented in this
publication.
PMID- 28403497
TI - ?
PMID- 28403498
TI - [Mental Health Services for Refugees].
PMID- 28403499
TI - ?
AB - Psycho-mental stressors and increased perceived stress in workplace settings may
determine the onset and course of stress-related mental and psychosomatic
disorders. For the description of psycho-mental stressors three distinct models
have widely been used in the analyses of the matter: the Demand-Control-Model by
Karasek and Theorell, the Effort-Reward-Imbalance Model by Siegrist, and the
Model of Organisational Justice.The interactional or social dimension in work
place settings can be seen as a cross-sectional dimension to the above mentioned
models. Here, social conflicts and mobbing, as specific forms of interactional
problems, are of importance.Besides measures of primary prevention which can be
derived from applying the above mentioned models, attention is paid increasingly
to secondary and tertiary preventive measures in work-place settings. Concepts
such as the psychosomatic consultation-hour within the context of workplace
showed to be effective measures for the early detection of people at risk or
early stages of e. g. stress-related psychosomatic disorders.Furthermore, step
wise reintegration of members of the work-force play an important role within the
effort to retain the ability to work and the workplace of individuals who
suffered from stress-related mental disorders, as it has to be stressed that
working and social interactions at the workplace may well be a resource that
enhances and stipulates psycho-mental well-being and mental health.This CME
Article describes the above mentioned models and discusses selected perspectives
of preventive measures to avoid stress-related mental disorders in members of the
work-force.
PMID- 28403500
TI - NIR Spectroscopy of Actaea racemosa L. rhizome - En Route to Fast and Low-Cost
Quality Assessment.
AB - Rhizomes of Actaea racemosa L. (formerly Cimicifuga racemosa) gained increasing
interest as a plant-derived drug due to its hormone-like activity and the absence
of estrogenic activity. According to the Current Good Manufacturing Practices
guidelines and pharmacopeial standards, quality assessment of herbal starting
materials includes tests on identity and substitution, as well as quantification
of secondary metabolites, usually by HPTLC and LC methods. To reduce the
laboratory effort, we investigated near-infrared spectroscopy for rapid species
authentication and quantification of metabolites of interest.Near-infrared
spectroscopy analysis is carried out directly on the milled raw plant material.
Spectra were correlated with reference data of polyphenols and triterpene
glycosides determined by LC/diode array detection and LC/evaporative light
scattering detection, respectively. Quantification models were built and
validated by cross-validation procedures. Clone plants, derived by vegetative
propagation, and plants of a collection from different geographical origins
cultivated in Berlin were analysed together with mixed batches from wild harvests
purchased at wholesalers.Generally, good to excellent correlations were found for
the overall content of polyphenols with coefficients of determination of R2 >
0.93. For individual polyphenols such as fukinolic acid, only models containing
clone plants succeeded (R2 > 0.92). For the total content of triterpene
glycosides, results were generally worse in comparison to polyphenols and were
observed only for the mixed batches (R2 = 0.93).Next to quantitative analysis,
near-infrared spectroscopy was proven as a rapid alternative to other, more
laborious methods for species authentication. Near-infrared spectroscopy was able
to distinguish different Actaea spp. such as the North American Actaea cordifolia
and the Asian Actaea cimicifuga, Actaea dahurica, Actaea heracleifolia, and
Actaea simplex.
PMID- 28403502
TI - [Innovative E-Health Approaches for Comorbid Depression in Patients with Obesity:
Patient and Expert Perspectives on User Acceptance].
AB - Objective Patients with chronic somatic diseases such as obesity often suffer
from comorbid depressive disorders and present a great challenge for the medical
health care system. The study aims to investigate the user acceptance of an
internet-based self-management program regarding depression (using the example of
MoodGYM) from two different perspectives: (A) the perspective of patients as well
as (B) the perspective of experts based on Rogers' 5 stages model of the
innovation-decision process (2003). Methods This study is following a qualitative
design including qualitative patient interviews (N = 7) and a focus group with
medical experts (N = 12). Results Internet-based self-management programs
represent a complementary treatment approach for patients and experts. Both
groups see the need for combining the topics overweight, activity, depression and
social interchange. Conclusion Patient and expert judgement showed a high degree
of user acceptance for internet-based self-management programs regarding
depression. The implementation of such programs within the medical care system of
patients with obesity should take physical and social aspects of the illness into
account.
PMID- 28403501
TI - Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation
of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata
Extracts.
AB - Boswellic acids constitute a group of unique pentacyclic triterpene acids from
Boswellia serrata with multiple pharmacological activities that confer them anti
inflammatory and anti-tumoral properties. A subgroup of boswellic acids,
characterized by an 11-keto group, elevates intracellular Ca2+ concentrations
[Ca2+]i and causes moderate aggregation of human platelets. How different BAs and
their mixtures in pharmacological preparations affect these parameters in
activated platelets has not been addressed, so far. Here, we show that boswellic
acids either antagonize or induce Ca2+ mobilization and platelet aggregation
depending on defined structural determinants with inductive effects predominating
for a B. serrata gum resin extract. 3-O-Acetyl-11-keto-beta-boswellic acid
potently suppressed Ca2+ mobilization (IC50 = 6 uM) and aggregation (IC50 = 1 uM)
when platelets were activated by collagen or the thromboxane A2 receptor agonist
U-46619, but not upon thrombin. In contrast, beta-boswellic acid and 3-O-acetyl
beta-boswellic acid, which lack the 11-keto moiety, were weak inhibitors of
agonist-induced platelet responses, but instead they elicited elevation of
[Ca2+]i and aggregation of platelets (>= 3 uM). 11-Keto-beta-boswellic acid, the
structural intermediate between 3-O-acetyl-11-keto-beta-boswellic acid and beta
boswellic acid, was essentially inactive independent of the experimental
conditions. Together, our study unravels the complex agonizing and antagonizing
properties of boswellic acids on human platelets in pharmacologically relevant
preparations of B. serrata gum extracts and prompts for careful evaluation of the
safety of such extracts as herbal medicine in cardiovascular risk patients.
PMID- 28403503
TI - [Psychiatry in East Germany (GDR) Between Awakening and Stagnation: The
Brandenburg Proposition to the "Therapeutic Community" (1974/76)].
AB - Inspired by the concept of the English psychiatrist Maxwell Jones, the
Brandenburg proposition or thesis towards the "Therapeutic Community" was
formulated in 1974. Its objective was to transform the therapeutic environment in
psychiatric hospitals of the German Democratic Republic (GDR). Based on sources
from the Federal Archive in Berlin and for the first time from the Historical
Archive of the Asklepios Hospital in Brandenburg, the motivation, implementation
and effect of the so-called Brandenburg proposition will be analysed within its
socio-political context. Although it was not able to exert a broader influence on
the provision of psychiatric care, important impulses for the development of
social psychiatry and psychotherapy in the GDR were nonetheless given. The
discussions on the concept of "therapeutic community" illustrated that this
concept was supposed to coincide with the socio-political objectives of the
Socialist Unity Party of Germany (SED) and their principles of collective
education.
PMID- 28403504
TI - Extracorporeal shock wave lithotripsy is safe and effective for pediatric
patients with chronic pancreatitis.
AB - Background and aims Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is
recommended as the first-line treatment for pancreatic stones. However, how well
P-ESWL performs in pediatric patients remains unclear. We aimed to evaluate the
safety and efficacy of P-ESWL for pediatric patients with chronic pancreatitis.
Methods This prospective observational study was conducted in patients with
painful chronic pancreatitis who underwent P-ESWL. Patients aged under 18 years
were included in the pediatric group; patients aged over 18 years who underwent P
ESWL in the same period were assigned to the control group. For investigation of
long-term follow-up, the pediatric group were matched with patients from the
control group in a 1:1 ratio. The primary outcomes were P-ESWL complications and
pain relief. The secondary outcomes included: stone clearance, physical and
mental health, quality of life score, and growth and developmental state. Results
From March 2011 to March 2015, P-ESWL was performed in 1135 patients (72 in the
pediatric group, 1063 in the control group). No significant differences were
observed in the occurrence of P-ESWL complications between the two groups (11.1 %
vs. 12.8 %; P = 0.68). Among the 67 pediatric patients (93.1 %) who underwent
follow-up for 3.0 years (range 1.3 - 5.2), complete pain relief was achieved in
52 patients (52 /67; 77.6 %); this value was not significantly different from
that of the matched controls (55 /69; 79.7 %; P = 0.94). Conclusions P-ESWL is
safe and effective for pediatric patients with chronic pancreatitis. It can
promote significant pain relief and stone clearance, and can benefit growth and
development.
PMID- 28403505
TI - The Role of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis of
Biliary Atresia: 14 Years' Experience.
AB - INTRODUCTION: Biliary atresia (BA) is a rare destructive inflammatory
obliterative cholangiopathy of neonates. Early diagnosis is important in disease
management. The aim was to evaluate the role of endoscopic retrograde
cholangiopancreatography (ERCP) in diagnosing BA in a large cohort. In addition,
we evaluated whether parameters such as bile trace, GGT, bilirubin, and
laboratory values in combination can be used to develop a risk score that could
indicate the referral to specialized centers. MATERIALS AND METHODS: All infants
with neonatal cholestasis (2000-2014) who presented to our endoscopy unit for
suspected BA were included. Demographics, laboratory parameters, ultrasound
findings, liver biopsy results, ERCP diagnosis, and surgical outcome were
collected. Value and safety of ERCP and risk factors for BA were retrospectively
analyzed. RESULTS: We included 251 infants in our cohort (55% males, median age:
53 days). BA was intraoperatively diagnosed in 155 (83.4%) patients and was
excluded in 30 (16.2%). Fifty-six cases were not operated due to the ERCP
findings. ERCP was successful in 224/251 patients (89.2%) with no procedure
related complications. The operative and endoscopic diagnosis matched in 96.6% of
the patients (positive predictive value: 92.2%, negative predictive value:
97.1%). In comparison to cases with excluded BA, the ones with this disease were
significantly associated with absence of duodenal bile traces (98.4 vs. 1.6%, p <
0.001), higher bilirubin (p < 0.001, cutoff 7.3 mg/dL), and higher GGT (p <
0.001, cutoff 250 U/L). CONCLUSION: ERCP is safe and accurate in the hands of
experts in diagnosing BA if the cause of cholestasis is unclear. While evaluating
the role of ERCP for diagnosing this disease, we found that the secondary
parameters GGT > 250 U/L, bilirubin > 7.3 mg/dL (125 MUmol/L), and the absence of
bile traces are risk factors.
PMID- 28403506
TI - Parasite responses to large mammal loss in an African savanna.
AB - Biodiversity loss can alter disease transmission; however, the magnitude and
direction of these effects vary widely across ecosystems, scales, and pathogens.
Here we experimentally examine the effects of one of the most globally pervasive
patterns of biodiversity decline, the selective loss of large wildlife, on
infection probability, intensity and population size of a group of common rodent
borne parasites - macroparasitic helminths. Consistent with previous work on
vector-borne pathogens, we found that large wildlife removal causes strong and
systematic increases of rodent-borne parasites, largely due to increases in
rodent density, as rodents are released from competition with larger herbivores.
Although we predicted that increased host density would also increase per capita
infection among all directly transmitted parasites, this additional amplification
occurred for only two of three examined parasites. Furthermore, the actual
effects of large mammal loss on per capita infection were mediated by the complex
suite of abiotic and biotic factors that regulate parasite transmission. Thus,
while these results strongly suggest that large wildlife loss will cause
systematic increases in rodent parasite populations, they also underscore the
difficulty of making more specific predictions for a given parasite based on
simple attributes such as transmission mode or life history strategy. Instead,
detailed information on the ecology of each parasite species would be necessary
to make more accurate predictions of how biodiversity loss will affect infection.
PMID- 28403507
TI - Endothelial dysfunction and mechanobiology in pathological cutaneous scarring:
lessons learned from soft tissue fibrosis.
AB - Hypertrophic scars/keloids are pathogenic scars that are characterized by
collagen and fibroblast accumulation. The endothelia in the lesions are
mechanosensitive and participate actively in the pathogenesis of these scars. The
present review summarizes how endothelium responds to mechanical stimuli such as
shear, stretch and hydrostatic pressure. It also shows that in heart, liver,
kidney and lung fibrosis, endothelial dysfunctions (EDs) associate with changes
in vascular tone, endothelial permeability, coagulation and vasomodulation that
result in inflammation, hypertension and coagulation. Pathological scars exhibit
similar EDs during their development and progression. Mechanopharmaceutical or
mechanotherapeutic interventions that rescue EDs may be useful scar treatments.
PMID- 28403508
TI - Impact of Transitional Care Services for Chronically Ill Older Patients: A
Systematic Evidence Review.
AB - Transitions in care from hospital to primary care for older patients with chronic
diseases (CD) are complex and lead to increased mortality and service use. In
response to these challenges, transitional care (TC) interventions are being
widely implemented. They encompass education on self-management, discharge
planning, structured follow-up and coordination among the different healthcare
professionals. We conducted a systematic review to determine the effectiveness of
interventions targeting transitions from hospital to the primary care setting for
chronically ill older patients.. Randomized controlled trials were identified
through Medline, CINHAL, PsycInfo, EMBASE (1995-2015). Two independent reviewers
performed the study selection, data extraction and assessment of study quality
(Cochrane "Risk of Bias"). Risk differences (RD) and number needed to treat (NNT)
or mean differences (MD) were calculated using a random-effects model. From
10,234 references, 92 studies were included. Compared to usual care,
significantly better outcomes were observed: a lower mortality at 3 (RD: -0.02 [
0.05, 0.00]; NNT: 50), 6, 12 and 18 months post-discharge, a lower rate of ED
visits at 3 months (RD: -0.08 [-0.15, -0.01]; NNT: 13), a lower rate of
readmissions at 3 (RD: -0.08 [-0.14, -0.03]; NNT: 7), 6, 12 and 18 months and a
lower mean of readmission days at 3 (MD: -1.33; [-2.15, -0.52]), 6, 12 and 18
months. No significant differences were observed in quality of life. In
conclusion, TC improves transitions for older patients and should be included in
the reorganization of healthcare services.
PMID- 28403509
TI - Uterine Rupture: What We Can Learn from an Ecological Study.
PMID- 28403511
TI - Decrease in serum IL-32 level in patients with atopic dermatitis after
cyclosporine treatment.
PMID- 28403512
TI - Mitotic figure in the peripheral blood smear.
PMID- 28403513
TI - A new negative and positive gas ion source for isotope ratio mass spectrometry.
AB - RATIONALE: The goal of this research was to construct an effective gas ion source
for isotope ratio mass spectrometry, which generates sufficiently strong and
stable ion beams for multiple isotope ratio analysis of sulfur and oxygen from
readily available gases such as SO2 , CO2 , CO, O2 and chlorine from CH3 Cl gas.
METHODS: By means of a 60 degrees sector mass spectrometer equipped with a new
type of sensitive ion source and with a dual-inlet system and triple collector
assembly, we have measured 34 S/32 S and challenging 36 S/32 S isotope ratios
using positive sulfur ions generated from SO2 gas. The new ion source differs
from the Nier-type ones by the electron beam being replaced with a tungsten
filament. The obtained isotope signals of 32 S+ , 34 S+ and 36 S+ were from 1 to
5 V (depending on the pressure of admitted gas) on high-ohm resistors of 200
MOmega, 5 GOmega and 500 GOmega, respectively. The variable 33 S peak was not
recorded as useful due to interference from H32 S+ ions. RESULTS: Although the
ionizing electrons in the new ion source have significant energy dispersion the
obtained peak profiles are flat-topped and they lead to good resolving power for
the mass spectrometer (M/?M ~ 100). The achieved precision of delta34 S and
delta36 S determination was better than +/-0.01 and +/-0.10/00, respectively. The
determination of 37 Cl/35 Cl in a volatile organic compound CH2 Cl2 was easily
achieved on Cl- negative ions with a precision of +/-0.0050/00. CONCLUSIONS: The
new ion source has great potential in the quantitative analysis of gases on
positive ion mass spectra as well as, in the case of gases with high electron
affinity such as CH3 Cl, CH3 Br, SF6 , SiF4 , on negative ones. It usefulness was
demonstrated on an example of multiple sulfur isotope analysis and 37 Cl/35 Cl
ratio determination with great precision. A negative ion source of this type will
probably be useful in a more complicated instruments used in SIMS or AMS.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28403510
TI - 'New to me': changing patient understanding of psoriasis and identifying
mechanisms of change. The Pso Well(r) patient materials mixed-methods feasibility
study.
AB - BACKGROUND: Psoriasis is an inflammatory long-term condition involving
comorbidities, unhealthy lifestyle and significant life impact. Patients'
understanding of psoriasis is limited and support lacking. The Common-Sense Model
of Self-Regulation of Health and Illness emphasizes the role of illness and
treatment beliefs on coping and self-management. New 'Pso Well(r) ' patient
materials informed by the model, addressed psoriasis as a long-term condition,
medication management and lifestyle behaviours. OBJECTIVES: To investigate
whether Pso Well(r) materials (i) broaden understanding of psoriasis without
increasing anxiety; (ii) are acceptable; and (iii) comprise features that appear
to effect change. METHODS: The Revised Illness Perceptions Questionnaire (IPQ-R
modified) and the Hospital Anxiety and Depression Scale (HADS) were administered
in patients before and after intervention. Numerical rating scales assessed
perceptions of change in understanding and anxiety resulting from engagement with
the materials. Qualitative interviews explored acceptability and perceived
'active ingredients'. RESULTS: Fifty-five patients completed pre- and
postintervention questionnaires (56% female; median age 59 years).
Postintervention, a large effect size was indicated in two IPQ-R domains -
illness coherence [t(55) = -3.48, P = 0.001 (two-tailed), eta2 = 0.19] and
personal control [t(55) = -2.98, P = 0.004 (two-tailed), eta2 = 0.14] - and a
medium effect in one, treatment control [t(55) = -2.08, P = 0.042 (two-tailed),
eta2 = 0.08]. HADS scores did not change. For numerical rating scales, 80% of
participants reported increased understanding of psoriasis and none reported
increased anxiety. Interviews with 19 patients indicated the materials were
acceptable and usable. Factors reported to broaden understanding and promote
engagement with self-management included linking of related disease aspects,
personally relevant content and high-quality design. CONCLUSIONS: High-quality,
theory-based psoriasis materials are acceptable to patients and can improve
understanding and sense of control without increasing anxiety.
PMID- 28403514
TI - The Precautionary Principle Has Not Been Shown to Be Incoherent: A Reply to
Peterson.
AB - In this journal, I have objected to Peterson's 2006 claim that the precautionary
principle is an incoherent decision rule. I defend my objections to Peterson's
recent replies, and I still claim that the precautionary principle has not been
shown to be incoherent.
PMID- 28403515
TI - An aggressive multifocal primary CNS histiocytosis with PTPN11 (Shp2) mutation.
PMID- 28403516
TI - Anisotropic Polymer Nanoparticles with Tunable Emission Wavelengths by
Intersegmental Chain Packing.
AB - The shape of nanoparticles is decisive for their self-assembly properties, as
well as for the behavior of individual particles in many instances. The
introduction and control of anisotropy is well-known for inorganic nanocrystals
but a largely unresolved problem for polymer nanoparticles, especially for
conjugated polymers. Here, we report a reproducible preparation method using
heterophase polymerization for a range of stable dispersions of ellipsoidal
conjugated polymer nanoparticles with sizes in the range of 50 to 180 nm and
narrow size and shape distributions. The nanoparticles show a bright fluorescence
with tunable emission wavelengths and quantum yields as high as phi=78 %.
Structural investigations reveal the nanoparticles to be composed of a highly
ordered beta- and alpha'-phase within a nematic matrix. Preliminary studies on
the origin of particle anisotropy suggest a concerted mechanism in which
anisotropic shape evolves from intersegmental packing that occurs along with
progressing chain formation by polymerization.
PMID- 28403517
TI - Reflectance confocal microscopy of vulvar epithelial neoplasia: a pilot study.
PMID- 28403518
TI - Formation of the IGF1R/CAV1/SRC tri-complex antagonizes TRAIL-induced apoptosis
in gastric cancer cells.
AB - Lipid rafts provide a biological platform for apoptosis induced by tumor necrosis
factor-related apoptosis-inducing ligand (TRAIL). We previously reported that
insulin-like growth factor 1 receptor (IGF1R) translocation into lipid rafts
helped to explain TRAIL resistance. However, it was not clear whether TRAIL
resistance was caused by the interaction of IGF1R with caveolin-1 (CAV1) and the
non-receptor tyrosine kinase SRC in lipid rafts of gastric cancer cells. Here, we
observed high IGF1R expression in TRAIL-resistant gastric cancer cells, and
showed that IGF1R combined with both CAV1 and SRC in a native complex. TRAIL was
shown to promote the formation of the IGF1R/CAV1/SRC tri-complex and the
activation of these three molecules. Knockdown of IGF1R or CAV1 or inhibition of
SRC activity reduced the formation of this tri-complex and enhanced TRAIL-induced
apoptosis. Furthermore, the overexpression of microRNA-194 reversed TRAIL
resistance by reducing IGF1R expression. In summary, TRAIL increased formation of
the IGF1R/CAV1/SRC tri-complex and the activation of downstream survival
pathways, leading to TRAIL resistance in gastric cancer cells.
PMID- 28403519
TI - Decadal declines in avian herbivore reproduction: density-dependent nutrition and
phenological mismatch in the Arctic.
AB - A full understanding of population dynamics depends not only on estimation of
mechanistic contributions of recruitment and survival, but also knowledge about
the ecological processes that drive each of these vital rates. The process of
recruitment in particular may be protracted over several years, and can depend on
numerous ecological complexities until sexually mature adulthood is attained. We
addressed long-term declines (23 breeding seasons, 1992-2014) in the per capita
production of young by both Ross's Geese (Chen rossii) and Lesser Snow Geese
(Chen caerulescens caerulescens) nesting at Karrak Lake in Canada's central
Arctic. During this period, there was a contemporaneous increase from 0.4 to 1.1
million adults nesting at this colony. We evaluated whether (1) density-dependent
nutritional deficiencies of pre-breeding females or (2) phenological mismatch
between peak gosling hatch and peak forage quality, inferred from NDVI on the
brood-rearing areas, may have been behind decadal declines in the per capita
production of goslings. We found that, in years when pre-breeding females arrived
to the nesting grounds with diminished nutrient reserves, the proportional
composition of young during brood-rearing was reduced for both species.
Furthermore, increased mismatch between peak gosling hatch and peak forage
quality contributed additively to further declines in gosling production, in
addition to declines caused by delayed nesting with associated subsequent
negative effects on clutch size and nest success. The degree of mismatch
increased over the course of our study because of advanced vegetation phenology
without a corresponding advance in Goose nesting phenology. Vegetation phenology
was significantly earlier in years with warm surface air temperatures measured in
spring (i.e., 25 May-30 June). We suggest that both increased phenological
mismatch and reduced nutritional condition of arriving females were behind
declines in population-level recruitment, leading to the recent attenuation in
population growth of Snow Geese.
PMID- 28403520
TI - Study of gene expression alteration in male androgenetic alopecia: evidence of
predominant molecular signalling pathways.
AB - BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss
in men. It is characterized by a distinct pattern of progressive hair loss
starting from the frontal area and the vertex of the scalp. Although several
genetic risk loci have been identified, relevant genes for AGA remain to be
defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS:
Molecular biomarkers associated with premature AGA were identified through gene
expression analysis using cDNA generated from scalp vertex biopsies of hairless
or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric
study reveals that genes encoding mast cell granule enzymes, inflammatory
mediators and immunoglobulin-associated immune mediators were significantly
overexpressed in AGA. In contrast, underexpressed genes appear to be associated
with the Wnt/beta-catenin and bone morphogenic protein/transforming growth factor
beta signalling pathways. Although involvement of these pathways in hair follicle
regeneration is well described, functional interpretation of the transcriptomic
data highlights different events that account for their inhibition. In
particular, one of these events depends on the dysregulated expression of
proopiomelanocortin, as confirmed by polymerase chain reaction and
immunohistochemistry. In addition, lower expression of CYP27B1 in patients with
AGA supports the notion that changes in vitamin D metabolism contributes to hair
loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular
events contributing to alopecia that may pave the way for new therapeutic
approaches.
PMID- 28403521
TI - Understanding management and support for domestic violence and abuse within
emergency departments: A systematic literature review from 2000-2015.
AB - AIMS AND OBJECTIVES: To identify, review and critically evaluate published
empirical studies concerned with the prevalence, management and support for
survivors of domestic violence and abuse who present at emergency department.
BACKGROUND: Domestic violence and abuse is a global phenomenon with a wealth of
studies that explore the different aspects of the issue including the economic,
social and health effects on survivors and on society as a whole. Emergency
department is widely recognised as one healthcare facility where domestic
violence and abuse survivors will often disclose domestic violence and abuse. In
the UK, National Institute of Clinical Excellence produced guidelines in 2014
requiring all sectors of health care and those they work alongside to recognise
support and manage survivors of domestic violence and abuse. Whilst there is an
increasing body of research on domestic violence and abuse, limited synthesised
work has been conducted in the context of domestic violence and abuse within
emergency department. DESIGN: This review encompasses empirical studies conducted
in emergency department for screening interventions, management and support for
domestic violence and abuse patients including prevalence. This review included
studies that included emergency department staff, emergency department service
users and domestic violence and abuse survivors. METHODS: A systematic approach
across five electronic bibliographic databases found 35 studies meeting the
inclusion criteria published between 2000-2015. RESULTS: From the 35 studies,
four descriptive overarching themes were identified (i) prevalence of domestic
violence and abuse in emergency department, (ii) use of domestic violence and
abuse screening tools and emergency department interventions, (iii) current
obstacles for staff working in emergency department and (iv) emergency department
users and survivor perspectives. CONCLUSIONS: Having knowledgeable and supportive
emergency department staff can have a positive benefit for the longer-term health
of the domestic violence and abuse survivor who seeks help. The physical
characteristics of domestic violence and abuse are often easier to identify and
manage, but emotional and psychological aspects of domestic violence and abuse
are often more complex and difficult for staff to identify. This therefore raises
questions as to what approaches can be used, within these busy settings, when
often survivors do not want to disclose. RELEVANCE TO CLINICAL PRACTICE: Domestic
violence and abuse has been shown to have a direct impact on the health and well
being of survivors who will often access emergency department services with
direct injuries and associated medical conditions. This article is relevant to
those working in the emergency department in raising awareness in a number of
areas of practice for example the prevalence of male intimate partner violence
survivors. Furthermore, patients do not always disclose domestic violence and
abuse even in cases where there is clear sustained injury thus requiring staff to
be vigilant to repeat attendees and patient history. This requires a well
maintained and effective reporting system for instances of suspected and
disclosed domestic violence and abuse in order that staff can provide the
appropriate care and support. Emergency department staff often deal with complex
cases, this includes different aspects of domestic violence and abuse including
physical, emotional and psychological abuse. Continual support and guidance,
including educational interventions, would assist emergency department clinical
staff to manage and discuss instances of domestic violence and abuse in their
workplace and their interactions with domestic violence and abuse patients.
Whilst training for emergency department staff is welcomed, there also needs to
be a greater awareness of the potential complexity of domestic violence and abuse
presentations beyond physical injury in order for staff to remain observant
throughout consultations. It is also suggested that clear domestic violence and
abuse assessment and referral mechanisms should be embedded into clinical
practice, including emergency department, as described in the UK National
Institute of Clinical Excellence guidelines (2014). Overall improvements in
reporting mechanisms in emergency department for the identification, management
and support for domestic violence and abuse survivors would add to the collective
and growing body of evidence surrounding domestic violence and abuse and their
presentations within healthcare settings. Such measures would enable those
working in emergency department to support disclosure of domestic violence and
abuse more effectively.
PMID- 28403522
TI - Structure-Activity Relationship Studies, SPR Affinity Characterization, and
Conformational Analysis of Peptides That Mimic the HNK-1 Carbohydrate Epitope.
AB - The design of molecules that mimic biologically relevant glycans is a significant
goal for understanding important biological processes and may lead to new
therapeutic and diagnostic agents. In this study we focused our attention on the
trisaccharide human natural killer cell-1 (HNK-1), considered the antigenic
determinant of myelin-associated glycoprotein and the target of clinically
relevant auto-antibodies in autoimmune neurological disorders such as IgM
monoclonal gammopathy and demyelinating polyneuropathy. We describe a structure
activity relationship study based on surface plasmon resonance binding affinities
aimed at the optimization of a peptide that mimics the HNK-1 minimal epitope. We
developed a cyclic heptapeptide that shows an affinity of 1.09*10-7 m for a
commercial anti-HNK1 mouse monoclonal antibody. Detailed conformational analysis
gave possible explanations for the good affinity displayed by this novel
analogue, which was subsequently used as an immunological probe. However,
preliminary screening indicates that patients' sera do not specifically recognize
this peptide, showing that murine monoclonal antibodies cannot be used as a guide
to select immunological probes for the detection of clinically relevant human
auto-antibodies.
PMID- 28403523
TI - Autologous cell suspension grafting in segmental vitiligo and piebaldism: a
randomized controlled trial comparing full surface and fractional CO2 laser
recipient-site preparations.
AB - BACKGROUND: Autologous noncultured cell suspension transplantation is an
effective treatment for repigmentation in segmental vitiligo and piebaldism. Full
surface laser ablation is frequently used to prepare the recipient site before
cell suspension transplantation, even though the optimal laser settings and
ablation depth are unknown. OBJECTIVES: To assess the efficacy and safety of less
invasive recipient-site preparations. METHODS: In a randomized, observer-blinded,
controlled trial we compared different recipient-site preparations before cell
suspension transplantation in segmental vitiligo and piebaldism. In each patient,
we randomly allocated three CO2 laser recipient-site preparations (209 and 144
MUm full surface, and fractional) and a control (no treatment) to four
depigmentations. After 6 months we assessed repigmentation and side-effects.
RESULTS: We included 10 patients with vitiligo (n = 3) and piebaldism (n = 7).
Compared with the control site, we found more repigmentation after full surface
ablation at 209 MUm (median 68.7%, P = 0.01) and 144 MUm (median 58.3%, P =
0.007), but no repigmentation after fractional ablation (median 0.0%, P = 0.14).
CONCLUSIONS: Superficial full surface ablation with a depth of 144 MUm is an
effective recipient-site preparation before cell suspension transplantation,
while fractional CO2 laser is not.
PMID- 28403524
TI - Human mesenchymal stem cells promote CD34+ hematopoietic stem cell proliferation
with preserved red blood cell differentiation capacity.
AB - Studies showed that co-transplantation of mesenchymal stem cells (MSCs) and cord
blood-derived CD34+ hematopoietic stem cells (HSCs) offered greater therapeutic
effects but little is known regarding the effects of human Wharton's jelly
derived MSCs on HSC expansion and red blood cell (RBC) generation in vitro. This
study aimed to investigate the effects of MSCs on HSC expansion and
differentiation. HSCs were co-cultured with MSCs or with 10% MSCs-derived
conditioned medium, with HSCs cultured under standard medium served as a control.
Cell expansion rates, number of mononuclear cell post-expansion and number of
enucleated cells post-differentiation were evaluated. HSCs showed superior
proliferation in the presence of MSC with mean expansion rate of 3.5 * 108 +/-
1.8 * 107 after day 7 compared to the conditioned medium and the control group
(8.9 * 107 +/- 1.1 * 108 and 7.0 * 107 +/- 3.3 * 106 respectively, P < 0.001).
Although no significant differences in RBC differentiation were observed between
groups at passage IV, the number of enucleated cell was greater compared to
earlier passages, indicating successful RBC differentiation. Cord blood-derived
CD34+ HSCs can be greatly expanded by co-culturing with MSCs without affecting
the RBC differentiation capability, suggesting the importance of direct MSC-HSCs
contact in HSC expansion and RBC differentiation.
PMID- 28403525
TI - Cyanomargarita gen. nov. (Nostocales, Cyanobacteria): convergent evolution
resulting in a cryptic genus.
AB - Two populations of Rivularia-like cyanobacteria were isolated from ecologically
distinct and biogeographically distant sites. One population was from an
unpolluted stream in the Kola Peninsula of Russia, whereas the other was from a
wet wall in the Grand Staircase-Escalante National Monument, a desert park-land
in Utah. Though both were virtually indistinguishable from Rivularia in field and
cultured material, they were both phylogenetically distant from Rivularia and the
Rivulariaceae based on both 16S rRNA and rbcLX phylogenies. We here name the new
cryptic genus Cyanomargarita gen. nov., with type species C. melechinii sp. nov.,
and additional species C. calcarea sp. nov. We also name a new family for these
taxa, the Cyanomargaritaceae.
PMID- 28403526
TI - CD105 expression in early erythroid precursors.
PMID- 28403527
TI - Basal cell carcinoma: CD56 and cytokeratin 5/6 staining patterns in the
differential diagnosis with Merkel cell carcinoma.
AB - BACKGROUND: Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC)
on histopathological examination and while CK20 is a useful marker in this
differential, it is occasionally negative in MCC. CD56, a sensitive marker of
neuroendocrine differentiation, is sometimes used to identify MCC, but has been
reportedly variably positive in BCC as well. In contrast, CK5/6 consistently
labels BCC but is not expressed in neuroendocrine tumors. METHODS: We evaluated
20 cases of BCC for the pattern of CD56 and cytokeratin 5/6 (CK5/6) staining,
hypothesizing that these 2 stains could differentiate BCC from MCC in difficult
cases. Seventeen cases of MCC previously stained with CD56 were also examined.
RESULTS: All BCCs showed patchy expression of CD56 except for 2 cases, which
showed staining of greater than 70% of tumor. CK5/6 was diffusely positive in all
cases of BCC. Fifteen of 17 MCCs were diffusely positive for CD56. The difference
in the pattern of CD56 expression between MCC and BCC (diffuse vs patchy,
respectively) was statistically significant (P < .05). CONCLUSION: BCC typically
shows patchy CD56 expression and diffuse CK5/6 positivity. These 2 markers can be
used to distinguish between BCC and MCC in challenging cases.
PMID- 28403528
TI - Superficial black onychomycosis due to Neoscytalidium dimidiatum.
PMID- 28403529
TI - New hydrocolloid-based emulsions for replacing fat in panna cottas: a structural
and sensory study.
AB - BACKGROUND: Dairy desserts are popular traditional products, but because of their
high calorie or fat content, they can be unsuitable for people who have certain
dietary requirements. The aim of this study was to design panna cottas with
similar organoleptic and textural properties to the traditional ones but with a
lower fat content, by replacing part of the cream with new emulsions prepared
with hydrocolloids (cellulose ethers), namely methylcellulose (MC) and
hydroxypropyl methylcellulose (HPMC). RESULTS: Incorporating the MC and HPMC
emulsions modified the textural properties (firmness and stiffness) of the panna
cottas. Regarding the sensory results, the panna cottas prepared with the MC and
HPMC emulsions were considered lumpy and soft respectively. CONCLUSION:
Considering the results as a whole, the cellulose type and the amount of cream
are factors to take into account. Although the texture and taste of the control
panna cotta are better than those of the panna cottas prepared with the MC and
HPMC emulsions, it is possible to replace 75% of the cream in traditional panna
cottas with HPMC emulsion and obtain good consumer acceptance and purchase
intention. The panna cottas with 75% substitution by HPMC emulsion were described
as creamy, with smooth appearance and moist mouth feel. (c) 2017 Society of
Chemical Industry.
PMID- 28403530
TI - Sociotechnical Resilience: A Preliminary Concept.
AB - This article presents the concept of sociotechnical resilience by employing an
interdisciplinary perspective derived from the fields of science and technology
studies, human factors, safety science, organizational studies, and systems
engineering. Highlighting the hybrid nature of sociotechnical systems, we
identify three main constituents that characterize sociotechnical resilience:
informational relations, sociomaterial structures, and anticipatory practices.
Further, we frame sociotechnical resilience as undergirded by the notion of
transformability with an emphasis on intentional activities, focusing on the
ability of sociotechnical systems to shift from one form to another in the
aftermath of shock and disturbance. We propose that the triad of relations,
structures, and practices are fundamental aspects required to comprehend the
resilience of sociotechnical systems during times of crisis.
PMID- 28403531
TI - Short-term effects of extracorporeal graft rinse versus circulatory graft rinse
in living donor liver transplantation. A prospective randomized controlled trial.
AB - Living donor liver transplantation has shorter cold ischemia time, less
preservative volume, and lower metabolic load compared to transplantation from
deceased donors. We investigated the impact of rinsing the graft contents into
the systemic circulation on operative course and postoperative outcomes. Donors
had right hepatectomy, and grafts were preserved with cold histidine-tryptophan
ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by
patient's portal blood either through incompletely anastomosed hepatic vein
(extracorporeal rinse group, EcRg, n = 40) or into systemic circulation
(circulatory rinse group, CRg, n = 40). The primary outcome objective was the
lowest mean arterial blood pressure within 5 min after portal unclamping as a
marker for postreperfusion syndrome (PRS). Secondary objectives included
hemodynamics and early graft's and patient's outcomes. Within 5 min
postreperfusion, mean arterial blood pressure was significantly lower in the CRg
compared to the EcRg, yet this was clinically insignificant. Postoperative graft
functions, early biliary and vascular complications, and three-month survival
were comparable in both groups. Rinsing the graft into the circulation increased
the incidence of PRS without significant impact on early graft or patient outcome
in relatively healthy recipients.
PMID- 28403533
TI - Towards satisfying performance of an O/W cosmetic emulsion: screening of
reformulation factors on textural and rheological properties using general
experimental design.
AB - OBJECTIVE: Consumers' demand for improved products' performance, alongside with
the obligation of meeting the safety and efficacy goals, presents a key reason
for the reformulation, as well as a challenging task for formulators. Any change
of the formulation, whether it is wanted - in order to innovate the product (new
actives and raw materials) or necessary - due to, for example legislative changes
(restriction of ingredients), ingredients market unavailability, new
manufacturing equipment, may have a number of consequences, desired or otherwise.
The aim of the study was to evaluate the influence of multiple factors -
variations of the composition, manufacturing conditions and their interactions,
on emulsion textural and rheological characteristics, applying the general
experimental factorial design and, subsequently, to establish the approach that
could replace, to some extent, certain expensive and time-consuming tests (e.g.
certain sensory analysis), often required, partly or completely, after the
reformulation. METHODS: An experimental design strategy was utilized to reveal
the influence of reformulation factors (addition of new actives, preparation
method change) on textural and rheological properties of cosmetic emulsions,
especially those linked to certain sensorial attributes, and droplet size.
RESULTS: The general experimental factorial design revealed a significant direct
effect of each factor, as well as their interaction effects, on certain
characteristics of the system and provided some valuable information necessary
for fine-tuning reformulation conditions. Upon addition of STEM-liposomes,
consistency, index of viscosity, firmness and cohesiveness were decreased, as
along with certain rheology parameters (elastic and viscous modulus), whereas
maximal and minimal apparent viscosities and droplet size were increased. The
presence of an emollient (squalene) affected all the investigated parameters in a
concentration-dependent manner. Modification of the preparation method (using
Ultra Turrax instead of a propeller stirrer) produced emulsions with higher
firmness and maximal apparent viscosity, but led to a decrease in minimal
apparent viscosity, hysteresis loop area, all monitored parameters of oscillatory
rheology and droplet size. CONCLUSION: The study showed that the established
approach which combines a general experimental design and instrumental,
rheological and textural measurements could be appropriate, more objective,
repeatable and time and money-saving step towards developing cosmetic emulsions
with satisfying, improved or unchanged, consumer-acceptable performance during
the reformulation.
PMID- 28403532
TI - Temozolomide increases MHC-I expression via NF-kappaB signaling in glioma stem
cells.
AB - Gliomas are the most common and primary tumors of the central nervous system in
adults. Temozolomide (TMZ) is the main drug used to treat glioma; however,
prognosis remains poor for most patients. Glioma stem cells (GSCs) are thought to
enable glioma initiation and evasion from immune surveillance; their
immunogenicity can be determined by expression of major histocompatibility
complex (MHC)-I. The present study investigated the effect of TMZ on MHC-I
expression in GSCs. Glioma spheres were cultured in serum-free medium containing
epidermal growth factor, basic fibroblast growth factor, and B27; MHC-I
expression was detected by immunocytochemistry, quantitative real-time PCR, and
flow cytometry. Nuclear factor (NF)-kappaB expression in glioma stem cells was
detected by Western blot. TMZ enhanced MHC-I expression in GSCs, and NF-kappaB
was activated. TMZ treatment increased MHC-I expression via modulation of NF
kappaB signaling in GSCs. In addition to being a chemotherapeutic agent, TMZ may
also serve as an immunomodulatory agent in the treatment of glioma patients.
PMID- 28403534
TI - The consistency of a species' response to press perturbations with high food web
uncertainty.
AB - Predicting species responses to perturbations is a fundamental challenge in
ecology. Decision makers must often identify management perturbations that are
the most likely to deliver a desirable management outcome despite incomplete
information on the pattern and strength of food web links. Motivated by a current
fishery decline in inland lakes of the Midwestern United States, we evaluate
consistency of the responses of a target species (walleye [Sander vitreus]) to
press perturbations. We represented food web uncertainty with 193 plausible
topological models and applied four perturbations to each one. Frequently the
direction of the focal predator response to the same perturbation is not
consistent across food web topologies. Simultaneous application of management
perturbations led to less consistent outcomes compared to the best single
perturbation. However, direct manipulation of the adult focal predator produced a
desirable outcome in 77% of 193 plausible topologies. Identifying perturbations
that produce consistent outcomes in the face of food web uncertainty can have
important implications for natural resource conservation and management efforts.
PMID- 28403536
TI - Enantiomeric NMR signal separation behavior and mechanism of samarium(III) and
neodymium(III) complexes with (S,S)-ethylenediamine-N,N'-disuccinate.
AB - Enantiomeric 1 H and 13 C NMR signal separation behaviors of various alpha-amino
acids and DL-tartarate were investigated by using the samarium(III) and
neodymium(III) complexes with (S,S)-ethylenediamine-N,N'-disuccinate as chiral
shift reagents. A relatively smaller concentration ratio of the lanthanide(III)
complex to substrates was suitable for the neodymium(III) complex compared with
the samarium(III) one, striking a balance between relatively greater signal
separation and broadening. To clarify the difference in the signal separation
behavior, the chemical shifts of beta-protons for fully bound D- and L-alanine
(deltab (D) and deltab (L)) and their adduct formation constants (Ks) were
obtained for both metal complexes. Preference for D-alanine was similarly
observed for both complexes, while it was revealed that the difference between
the deltab (D) and deltab (L) values is the significant factor to determine the
enantiomeric signal separation. The neodymium(III) and samarium(III) complexes
can be used complementarily for higher and smaller concentration ranges of
substrates, respectively, because the neodymium(III) complex gives the larger
difference between the deltab (D) and deltab (L) values with greater signal
broadening compared to the samarium(III) complex.
PMID- 28403535
TI - Assembly and comparison of two closely related Brassica napus genomes.
AB - As an increasing number of plant genome sequences become available, it is clear
that gene content varies between individuals, and the challenge arises to predict
the gene content of a species. However, genome comparison is often confounded by
variation in assembly and annotation. Differentiating between true gene absence
and variation in assembly or annotation is essential for the accurate
identification of conserved and variable genes in a species. Here, we present the
de novo assembly of the B. napus cultivar Tapidor and comparison with an improved
assembly of the Brassica napus cultivar Darmor-bzh. Both cultivars were annotated
using the same method to allow comparison of gene content. We identified genes
unique to each cultivar and differentiate these from artefacts due to variation
in the assembly and annotation. We demonstrate that using a common annotation
pipeline can result in different gene predictions, even for closely related
cultivars, and repeat regions which collapse during assembly impact whole genome
comparison. After accounting for differences in assembly and annotation, we
demonstrate that the genome of Darmor-bzh contains a greater number of genes than
the genome of Tapidor. Our results are the first step towards comparison of the
true differences between B. napus genomes and highlight the potential sources of
error in future production of a B. napus pangenome.
PMID- 28403537
TI - CDSpecTech: A single software suite for multiple chiroptical spectroscopic
analyses.
AB - The program CDSpecTech was developed to facilitate the analysis of chiroptical
spectra, which include the following: vibrational circular dichroism (VCD) and
corresponding vibrational absorption (VA) spectra; vibrational Raman optical
activity (VROA) and corresponding vibrational Raman spectra; electronic circular
dichroism (ECD) and corresponding electronic absorption (EA) spectra. In
addition, the program allows for generating optical rotatory dispersion (ORD) as
the Kramers-Kronig transform of ECD spectra. The simulation of theoretical
spectra from transition strengths can be achieved using different bandshape
profiles. The experimental and simulated theoretical spectra can be visually
compared by displaying them together. A unique feature of CDSpecTech is
performing spectral analysis using the ratio spectra; i.e., the dimensionless
dissymmetry factor (DF) spectrum, which is the ratio of CD to absorption spectra,
and the dimensionless circular intensity difference (CID) spectrum, which is the
ratio of VROA to vibrational Raman spectra. The quantitative agreement between
experimental and simulated theoretical spectra can also be assessed from the
numerical similarity overlap between them. Two different similarity overlap
methods are available. The program uses a graphical user interface which allows
for ease of use and facilitates the analysis. All these features make CDSpecTech
a valuable tool for the analysis of chiroptical spectra. The program is freely
available on the World Wide Web.
PMID- 28403538
TI - Human papillomavirus, Epstein-Barr virus, and methylation status of p16ink4a in
penile cancer.
AB - Little is known about penile carcinogenesis. The aim of this study was to
evaluate the prevalence of HPV and EBV, and the methylation status of p16ink4a in
penile cancer samples, and to contribute to the understanding of the mechanisms
responsible for penile cancer development. HPV DNA was detected in 63.6% of 122
cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%,
with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in
27.3% of the cases. Hypermethylation in p16ink4a was detected in 64.5% of 110
tested cases. An association between the absence of HPV absence and p16ink4a
hypermethylation was also found. Death and/or progressive disease was associated
with grade (P = 0.001), T stage (P < 0.0001), and N stage (P < 0.0001). In the
multivariable model, grade and N stage were independent risk factors for disease
free survival (P = 0.008 and P < 0.001, respectively). Patients without viral
infection had a median age significantly lower than that of the HPV-infected
patients. We suggest at least two pathways for penile carcinogenesis, one HPV
independent linked to epigenetic events, probably via p16ink4a inactivation; and
another, dependent on HPV infection.
PMID- 28403539
TI - Guanosine-5'-Monophosphate Polyamine Hybrid Hydrogels: Enhanced Gel Strength
Probed by z-Spectroscopy.
AB - The self-assembling tendencies of guanosine-5'-monophosphate (GMP) can be
drastically increased using polyamines, with potential applications in the
production of biocompatible smart materials, as well as for the design of
antitumor drugs based on G-quadruplex stabilization. Results from scanning
electron microscopy (SEM), wide angle X-ray scattering (WAXS), rheology, and
nuclear magnetic resonance (NMR) z-spectroscopy studies are presented.
PMID- 28403540
TI - Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all-cause
mortality in hemodialysis patients: A prospective cohort study.
AB - INTRODUCTION: Patients with chronic kidney disease, especially those with end
stage renal disease, have an increased risk of death. Previous studies have
suggested neutrophil/lymphocyte ratio (NLR) was related to worse outcome in
patients undergoing hemodialysis (HD). However, monocyte/lymphocyte ratio (MLR)
has not been evaluated in HD patients. In this study, we prospectively studied
the predictive value of MLR for all-cause and cardiovascular mortality in HD
patients and compared it with NLR. METHODS: Patients who had been on a HD
treatment for at least 6 months were enrolled. MLR was calculated by dividing the
monocyte count by the lymphocyte count. Survival outcomes were estimated using
the Kaplan-Meier method and compared by the log-rank test. Univariate and
multivariate analyses were performed to evaluate the prognostic impact of MLR and
other clinical factors on all-cause and cardiovascular mortality. RESULTS:
Mortality rates for the lowest, middle, and highest MLR tertile group were 3.65,
7.02, and 11.15, respectively per 100 patient-years. The Kaplan-Meier analysis
revealed that survival rates were significantly different among three MLR groups
(P < 0.001). In multivariate Cox regression analyses, MLR was independently
associated with all-cause mortality (HR 4.842; 95% CI, 2.091-11.214; P < 0.001)
and cardiovascular mortality (HR 6.985, 95% CI 1.943-25.115, P = 0.003) as
continuous variables. NLR was not an independent predictor of all-cause nor
cardiovascular mortality after adjusted with MLR. CONCLUSIONS: The main finding
of the study suggest that higher MLR was a strong and independent predictor of
all-cause and cardiovascular mortality and overwhelmed NLR among HD patients.
PMID- 28403541
TI - Histopathological evaluation of pretransplant donor biopsies in expanded criteria
donors with high kidney donor profile index: a retrospective observational cohort
study.
AB - There is no consensus on the allocation of renal transplants from expanded
criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the
need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on
Remuzzi Score (RS) allows identification of those marginal kidneys in the highest
calculated KDPI risk group (>91%) that appropriate for single transplantation. A
retrospective study was conducted of 485 consecutive kidneys procured from a
single center and transplanted if the RS was <=4. We compared 5-year kidney and
patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI
group. The median KDPI (interquartile range) was 71 (66-76) for KDPI <80% (n =
77), 86 (81-90) for KDPI 81-90% (n = 82), and 97 (94-100) for KDPI >91% (n =
205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and
death-censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively
for each KDPI group. In >91% calculated KDPI group, there were no differences in
graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of
PTDB based on RS used for allocation of organs with the highest KDPI range could
support to the acceptance of suitable organs for single transplantation with good
patient and graft survival rate.
PMID- 28403542
TI - Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid
chromatography with tandem mass spectrometric detection after precolumn chiral
derivatization.
AB - Ammuxetine (AMT), a novel chiral antidepressant candidate compound, exhibits
better antidepression effects than duloxetine in different animal models. In this
article, a chiral derivatization method, combined with online solid phase
extraction (online SPE) and liquid chromatography-tandem mass spectrometry (LC
MS/MS), was developed for the chiral separation of AMT enantiomers after
administration of racemic AMT to dogs. The derivatization reaction employed
2,3,4,6-tetra-O-acetyl-b-glucopyr-anosyl isothiocyanate (GITC) as a precolumn
chiral derivatization reagent. A SPE column Retain PEP Javelin (10 * 2.1 mm) was
used to remove proteins and other impurities in plasma samples. The enantiomeric
derivatives were separated on a ZORBAX SB-C18 column (50 * 2.1 mm * 3.5 MUm) with
an isocratic elution procedure. The selected multiple reaction monitoring mode of
the positive ion was performed and the parent to the product transitions m/z
681.0/543.1 and m/z 687.4/543.1 were used to measure the derivatives of AMT and
duloxetine (internal standard) with electrospray ionization. The method was
validated in terms of specificity, linearity, sensitivity, precision, accuracy,
matrix effect, and stability. The method was applied to a pharmacokinetics study
of AMT racemate in dogs. The results suggested that the pharmacokinetic of AMT
enantiomers might be stereoselective in dogs.
PMID- 28403543
TI - Responses of plant phenology, growth, defense, and reproduction to interactive
effects of warming and insect herbivory.
AB - Climate warming can modify plant reproductive fitness through direct and indirect
pathways. Direct effects include temperature-driven impacts on growth,
reproduction, and secondary metabolites. Indirect effects may manifest through
altered species interactions, including herbivory, although studies comparing the
interactive effects of warming and herbivory are few. We used experimental
warming combined with herbivore exclusion cages to assess the interactive effects
of climate warming and herbivory by Popillia japonica, the Japanese beetle, on
flowering phenology, growth, defense, and lifetime reproduction of a biennial
herb, Oenothera biennis. Regardless of temperature, herbivory delayed flowering
phenology and, surprisingly, led to decreased levels of foliar defenses. At
ambient temperatures, plants were able to compensate for herbivory by producing
smaller seeds and increasing total seed production, leading to similar investment
in seed biomass for plants exposed to and protected from herbivores. At elevated
temperatures, plants had elevated total seed production, but herbivory had
negligible impacts on flower and fruit production, and total lifetime seed
biomass was highest in plants exposed to herbivores in warmed conditions. We
speculate that warming induced a stress response in O. biennis resulting from low
soil moisture, which in turn led to an increase in seed number at the expense of
maternal investment in each seed. Plant-insect interactions might therefore shift
appreciably under future climates, and ecologists must consider both temperature
and herbivory when attempting to assess the ramifications of climate warming on
plant populations.
PMID- 28403544
TI - Spider (Arachnida, Araneae) diversity in secondary and old-growth southern
Atlantic forests of Parana state, Brazil.
AB - The data presented here have been collected in the southern part of the Atlantic
Forest (Mata Atlantica) in the state of Parana, Brazil within a bilateral
scientific project (SOLOBIOMA). The project aimed to assess the quality of
secondary forests of different regeneration stages in comparison with old-growth
forests with regard to diversity of soil animals and related functions. The
Atlantic Forest is a hotspot of biological diversity with an exceptionally high
degree of endemic species, extending over a range of 3,500 km along the coast of
Brazil. The anthropogenic pressure in the region is very high with three of the
biggest cities of Brazil (Sao Paulo, Rio de Janeiro, and Curitiba) lying in its
extension. An evaluation of the value of secondary forests for biodiversity
conservation is becoming more and more important due to the complete
disappearance of primary forests. In 2005, we sampled spiders in 12 sites of
three successional stages (5-8, 10-15, 35-50 yr old, three replicates of each
forest stage) and old-growth forests (> 100 yr untouched, also three replicates).
All sites were inside a private nature reserve (Rio Cachoeira Nature Reserve). We
repeated the sampling design and procedure in 2007 in a second private reserve
(Itaqui Nature Reserve). The two nature reserves are within about 25 km of each
other within a well preserved region of the Mata Atlantica, where the matrix of
the landscape mosaic is still forest. A widely accepted standard protocol was
used in a replicated sampling design to apply statistical analyses to the
resulting data set and allow for comparison with other studies in Brazil. Spiders
were sorted to family level and counted; the adult spiders further identified to
species if possible or classified as morphospecies with the help of several
spider specialists.
PMID- 28403545
TI - Phenotypic spectrum of autosomal recessive congenital ichthyosis due to PNPLA1
mutation.
PMID- 28403546
TI - Downregulation of delta-aminolevulinate dehydratase is associated with poor
prognosis in patients with breast cancer.
AB - Delta-aminolevulinate dehydratase (ALAD) catalyzes the second step in the
biosynthesis of heme and is also an endogenous inhibitor of the 26S proteasome.
The role of ALAD in breast cancer progression is still unclear. In this study, we
found that the expression of ALAD was downregulated in breast cancer tissues
compared with adjacent normal breast tissues. Enhanced ALAD expression was
associated with a favorable outcome in patients with breast cancer.
Overexpression of ALAD suppresses breast cancer cell proliferation and invasion
and inhibits the epithelial-mesenchymal transition phenotype. Furthermore, we
found that ALAD regulates transforming growth factor-beta-mediated breast cancer
progression. This finding suggests that ALAD might be a potential biomarker for
breast cancer that suppresses breast cancer progression by regulating
transforming growth factor-beta-mediated epithelial-mesenchymal transition.
PMID- 28403547
TI - Retracted: Effects of dietary supplementation with a probiotic (Enterococcus
faecium DSM 7134) on growth performance, nutrient digestibility, and gut health
status in weaning pigs.
PMID- 28403548
TI - Protein-arginine deiminase 2 suppresses proliferation of colon cancer cells
through protein citrullination.
AB - Expression of the gene for protein-arginine deiminase 2 (PADI2) has been shown to
be downregulated in colon cancer, with such downregulation being indicative of a
poor prognosis in individuals with this disease. We have now examined the
expression of PADI2 in matched colon cancer and normal colon tissue specimens as
well as in colon cancer cell lines. We found that isoform 1 of PADI2 is the
predominant isoform in colon tissue and is downregulated during colon
carcinogenesis. Immunohistochemical analysis showed that PADI2 is expressed in
normal colonic epithelial cells. Overexpression of PADI2 isoform 1 suppressed the
proliferation of colon cancer cells in vitro in association with increased
protein citrullination. Expression of a catalytically inactive mutant (C647A) of
PADI2 or of PADI2 isoform 2 did not induce such effects, indicating that the
protein citrullination activity of PADI2 is required for inhibition of cell
growth. The growth defect induced by PADI2 was not attributable to increased
apoptosis but rather was accompanied by arrest of cell cycle progression in G1
phase. Finally, we detected citrullinated proteins in normal colon tissue by
immunoblot analysis. Our data thus suggest that PADI2 suppresses the
proliferation of colonic epithelial cells through catalysis of protein
citrullination, and that downregulation of PADI2 expression might therefore
contribute to colon carcinogenesis.
PMID- 28403549
TI - Chaotropic heat treatment resolves native-like aggregation of a heterologously
produced hyperthermostable laminarinase.
AB - Production of hyperthermostable enzymes in mesophilic hosts frequently causes
undesired aggregation of these proteins. During production of Pyrococcus furiosus
endo-beta-1,3 glucanase (LamA) in Escherichia coli, soluble and insoluble species
form. Here, the authors address the composition of this mixture, including the
nature of LamA conformers, and establish a method to increase the yield of native
monomer. With gel electrophoresis, size-exclusion chromatography, light
scattering, circular dichroism and enzyme kinetics the authors show that
approximately 50 % of heterologously produced LamA is soluble, and that 40 % of
this fraction constitutes native-like oligomers and non-native monomers. Soluble
oligomers display, like native LamA monomer, substrate inhibition, although with
poor activity. Treatment of soluble oligomers with 3 M guanidinium hydrochloride
at 80 degrees C yields up to 75 % properly active monomer. Non-native monomer
shows low specific activity without substrate inhibition. Incubating non-native
monomer with 3 M guanidinium hydrochloride at 80 degrees C causes formation of
25 % native LamA. Also, a large amount of insoluble LamA aggregates can be
converted into soluble native monomer by application of this procedure. Thus,
chaotropic heat treatment can improve the yield and quality of hyperthermostable
proteins that form aberrant species during production in E. coli.
PMID- 28403550
TI - Density functional theory study on structure and stability of BeBn+ clusters.
AB - RATIONALE: Boride compounds hold promise for broad applications in the field of
optoelectronics due to their high-temperature resistant, corrosion resistant and
antioxidant properties. In order to reveal the formation mechanism of alkali and
alkaline earth metal doped boron clusters, theoretical studies of these systems
are required. METHODS: All the possible geometrical structures of BeBn+ clusters
(n = 1-8) were optimized at the B3LYP/6-311+G(d) level; the harmonic vibration
frequencies were obtained to examine the true stability and give the zero-point
vibration energy at that theoretical level. The single point energies of all the
structures were computed at the CCSD(T)/aug-cc-pVDZ level. For the most stable
structures, the average binding energy (Eb ), the fragmentation energy (EF ) and
second-order difference of total energy (Delta2 E) were used to evaluate the
relative stability of clusters. RESULTS: Most of the BeBn+ clusters are planar in
structure; the B atoms tend to aggregate to form a boron ring, and the
coordinating Be atoms are on the periphery of the clusters. The fragmentation
energy and second-order difference of total energy show that there is an obvious
odd-even alteration as n increases, and local-maxima when n is odd. CONCLUSIONS:
A systematic theoretical investigation on the geometries, stabilities and
electronic properties of BeBn+ clusters has been carried out where n = 1-8. The
results provide a useful reference for understanding the formation mechanism and
stability of these clusters, as well as guidance for finding larger size
clusters.
PMID- 28403551
TI - Cyclic electron flow, NPQ and photorespiration are crucial for the establishment
of young plants of Ricinus communis and Jatropha curcas exposed to drought.
AB - Although plant physiological responses to drought have been widely studied, the
interaction between photoprotection, photorespiration and antioxidant metabolism
in water-stressed plants is scarcely addressed. This study aimed to evaluate the
physiological adjustments preserving photosynthesis and growth in two plant
species with different tolerance to drought: Jatropha curcas and Ricinus
communis. We measured stress indicators, gas exchange, photochemistry of PSII and
PSI, antioxidant enzymes, cyclic electron flow and photorespiration.
Physiological stress indicators associated with reduction in growth confirmed R.
communis as sensitive and J. curcas as tolerant to drought. Drought induced loss
of photosynthesis in R. communis, whereas J. curcas maintained higher leaf gas
exchange and photochemistry under drought. In addition, J. curcas showed higher
dissipation of excess energy and presented higher cyclic electron flow when
exposed to drought. Although none of these mechanisms have been triggered in R.
communis, this species showed increases in photorespiration. R. communis
displayed loss of Rubisco content while the Rubisco relative abundance did not
change in J. curcas under drought. Accordingly, the in vivo maximum Rubisco
carboxylation rate (Vcmax ) and the maximum photosynthetic electron transport
rate driving RuBP regeneration (Jmax ) were less affected in J. curcas. Both
species displayed an efficient antioxidant mechanism by increasing activities of
ascorbate peroxidase (APX) and superoxide dismutase (SOD). Overall, we suggest
that the modulation of different photoprotective mechanisms is crucial to
mitigate the effects caused by excess energy, maintaining photosynthetic
apparatus efficiency and promoting the establishment of young plants of these two
species under drought.
PMID- 28403552
TI - Rapid mass spectrometry analysis of a rectilinear ion trap by continuous secular
frequency scanning.
AB - RATIONALE: Secular frequency scanning is a mass spectrometry (MS) analysis method
in which the frequency of the auxiliary alternating current (AC) signal is
scanned. It has low requirements for radio-frequency (RF) power, which is
beneficial for the miniaturization of the mass spectrometer. In this study, the
MS performance in the reverse secular frequency scanning (RSFS) mode is optimized
for a rectilinear ion trap (RIT), and a method for rapid MS analysis using
continuous secular frequency scanning (CSFS) is proposed. METHODS: A RIT mass
spectrometer with an auxiliary AC frequency scanning function was built. The
resolution, tandem mass spectrometry (MS/MS) and quantitation capability in the
RSFS mode were characterized and optimized. Operation in the CSFS mode was then
performed by scanning the frequency of the auxiliary AC signal continuously and
periodically while maintaining the RF signal and the front Z electrode in the ion
injection state, so that the ion injection and cooling were performed at the same
time as the mass analysis. RESULTS: With this system, the RSFS mode achieved unit
mass resolution at 332 Th, and the MS/MS analysis was completed without changing
the RF amplitude at q = 0.4583 for reserpine. The limit of quantitation for
imatinib was about 250 ng/mL with the determination coefficient R2 = 0.9981. In
the CSFS mode, a single analysis cycle of less than 20 ms could be achieved,
which is 14 times faster than the traditional sweep modes. In addition, 100% ion
utilization can theoretically be achieved in the CSFS mode. CONCLUSIONS: The CSFS
mode is different from the traditional phased sequential operation mode of an ion
trap mass spectrometer. By periodic scanning of the auxiliary AC frequency while
maintaining ion injection, it is possible to improve the analysis efficiency of
the mass spectrometer, which has the prospect of useful application in the field
of rapid MS monitoring. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28403553
TI - Highly enantioselective asymmetric direct aldol reaction promoted by aziridine
amides constructed on chiral terpene scaffold.
AB - Optically pure, diastereomeric aziridine amides built on the chiral skeletons of
camphor, fenchone, and menthone have proven to be highly efficient ligands for
enantioselective asymmetric direct aldol reaction in the presence of water and
zinc triflate. Desired products were formed in moderate to high chemical yields
(up to 95%) and with enantiomeric excess up to 99%. The influence of the
stereogenic centers located at the aziridine subunit on the stereochemical course
of the reaction is discussed.
PMID- 28403554
TI - Continuous Veno-Venous Hemofiltration Improves Survival of Patients With
Congestive Heart Failure and Cardiorenal Syndrome Compared to Slow Continuous
Ultrafiltration.
AB - Continuous veno-venous hemofiltration (CVVH) could modulate the inflammatory
response by removal of circulating cytokines and therefore improve cardiac
function in patients with heart failure (HF). We hypothesized that patients with
developed cardiorenal syndrome and treated with CVVH have lower risk for
mortality than other patients treated with slow continuous ultrafiltration
(SCUF). This was a prospective, longitudinal follow-up study for 24 months
duration. In total, 120 patients were recruited from the intensive care units.
Only patients with cardiorenal syndrome type 1 and 2 were enrolled. 54 CVVH and
23 SCUF patients survived. Mean survival time was longer in CVVH group with
cardiomyopathy than in the SCUF group. When we compared patients with
cardiomyopathy and hourly urine output <10 mL/h, mean survival time was
significantly longer in patients treated with CVVH. This is the first study to
analyze the impact of different CRRT modalities (CVVH vs. SCUF) on survival of
patients with HF and who developed cardiorenal syndrome. Better survival in
patients treated with CVVH, which is mostly pronounced in patients with
cardiomyopathy, is a consequence of a better preserved hourly urine output.
Longer survival in patients with cardiomyopathy is most probably related to
cytokine removal by CVVH with smaller UF rates and longer duration of each
treatment. Slow continuous ultrafiltration remains the method of choice in
patients with HF and preserved renal function but in cases of developed
cardiorenal syndrome is much inferior to CVVH.
PMID- 28403555
TI - Seasonal fecundity and costs to lambda are more strongly affected by direct than
indirect predation effects across species.
AB - Increased perceived predation risk can cause behavioral and physiological
responses to reduce direct predation mortality, but these responses can also
cause demographic costs through reduced reproductive output. Such indirect costs
of predation risk have received increased attention in recent years, but the
relative importance of direct vs. indirect predation costs to population growth
(lambda) across species remains unclear. We measured direct nest predation rates
as well as indirect benefits (i.e., reduced predation rates) and costs (i.e.,
decreased reproductive output) arising from parental responses to perceived
offspring predation risk for 10 songbird species breeding along natural gradients
in nest predation risk. We show that reductions in seasonal fecundity from
behavioral responses to perceived predation risk represent significant
demographic costs for six of the 10 species. However, demographic costs from
these indirect predation effects on seasonal fecundity comprised only 12% of
cumulative predation costs averaged across species. In contrast, costs from
direct predation mortality comprised 88% of cumulative predation costs averaged
across species. Demographic costs from direct offspring predation were relatively
more important for species with higher within-season residual-reproductive value
(i.e., multiple-brooded species) than for species with lower residual
reproductive value (i.e., single-brooded species). Costs from indirect predation
effects were significant across single- but not multiple-brooded species.
Ultimately, demographic costs from behavioral responses to offspring predation
risk differed among species as a function of their life-history strategies. Yet
direct predation mortality generally wielded a stronger influence than indirect
effects on seasonal fecundity and projected lambda across species.
PMID- 28403556
TI - Assessment of endogenous 25-hydroxyvitamin D serum concentrations by liquid
chromatography-tandem mass spectrometry in various animal species.
AB - BACKGROUND: Mass spectrometry (MS) has become the preferential method for the
analysis of vitamin D in the clinic, yet no single platform is utilized for
preclinical species in drug development studies. For vitamin D, the MS platform
can provide certain benefits such as applicability of a single assay for multiple
species, low cost, and high specificity. OBJECTIVES: A quantitative liquid
chromatography-tandem MS (LC-MS/MS) assay for 25-hydroxyvitamin D3 (25OHD3 ) and
D2 (25OHD2 ) was validated for rat, dog, mouse, and monkey, and suitability for
drug development studies was assessed. METHODS: Standards were used to determine
intra- and inter-assay accuracy and precision for LC-MS/MS. Extraction recovery
and carryover due to instrumentation were determined. Repeat analyses of pooled
serum samples from rat, dog, mouse, and monkey were assessed for precision, and
other serum samples were used to determine the normal range in each species and
detect biologically relevant changes. RESULTS: For both 25OHD3 and 25OHD2 ,
inaccuracy was <= 6%, and imprecision was <= 13%. Extraction recovery was 75% for
25OHD3 and 72% for 25OHD2 , and carryover was <= 0.1%. Measurable concentrations
of 25OHD3 were recorded in serum samples from all species tested, but no 25OHD2
as diets were only fortified with 25OHD3 . This dataset provides preliminary
information for the determination of RIs for 25OHD3 in rat, dog, mouse, and
monkey with the LC-MS/MS platform. CONCLUSIONS: The LC-MS/MS assay was accurate
and precise for determination of endogenous concentrations of 25OHD3 in serum
samples from drug development studies in rat, dog, mouse, and monkey.
PMID- 28403557
TI - Research funding: do you get what you pay for?
PMID- 28403558
TI - Glutathione biosynthesis and activity of dependent enzymes in food grade lactic
acid bacteria harboring multidomain bifunctional fusion gene (gshF).
AB - AIMS: To assess glutathione (GSH) biosynthesis ability and activity of dependent
enzymes in food grade lactic acid bacteria and correlating with genomic
information on glutathione system in LAB. METHODS AND RESULTS: Whole genome
sequences of twenty-six food grade LAB were screened for presence/absence of set
of genes involved in de novo glutathione system. Multiple strains of S.
thermophilus (37), Lb. casei (37), Lb. rhamnosus (4), Lb. paracasei (8) Lb.
plantarum (23) & Lb. fermentum (22) were screened for biochemical evidence of GSH
system. Multiple sequence analysis of GshF sequences was carried out for
comparing the genomic signatures between GSH producing and non-producing species.
CONCLUSIONS: Streptococcus thermophilus was found to have de novo glutathione
biosynthesis as well as import ability. Lactobacillus spp. were negative for GSH
synthesis but could import it from the medium. All the species exhibited prolific
glutathione reductase and peroxidase activity. Sequence analysis revealed absence
of key amino acid residues as well as a truncated N-terminal region in
lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides a
comprehensive view on status of an important antioxidative system (the
glutathione system) in LAB and is expected to serve as a primer for future work
on mechanistic role of GSH in the group. This article is protected by copyright.
All rights reserved.
PMID- 28403560
TI - Icons in paediatrics: Rolf Kostmann (1909-1982).
PMID- 28403559
TI - An Integrin-Targeting RGDK-Tagged Nanocarrier: Anticancer Efficacy of Loaded
Curcumin.
AB - Herein we report the design and development of alpha5 beta1 integrin-specific
noncovalent RGDK-lipopeptide-functionalized single-walled carbon nanotubes
(SWNTs) that selectively deliver the anticancer drug curcumin to tumor cells.
RGDK tetrapeptide-tagged amphiphiles were synthesized that efficiently disperse
SWNTs with a suspension stability index of >80 % in cell culture media. 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)- and lactate
dehydrogenase (LDH)-based cell viability assays in tumor (B16F10 melanoma) and
noncancerous (NIH3T3 mouse fibroblast) cells revealed the non-cytotoxic nature of
these RGDK-lipopeptide-SWNT conjugates. Cellular uptake experiments with
monoclonal antibodies against alphav beta3 , alphav beta5 , and alpha5 beta1
integrins showed that these SWNT nanovectors deliver their cargo (Cy3-labeled
oligonucleotides, Cy3-oligo) to B16F10 cells selectively via alpha5 beta1
integrin. Notably, the nanovectors failed to deliver the Cy3-oligo to NIH3T3
cells. The RGDK-SWNT is capable of delivering the anticancer drug curcumin to
B16F10 cells more efficiently than NIH3T3 cells, leading to selective killing of
B16F10 cells. Results of Annexin V binding based flow cytometry experiments are
consistent with selective killing of tumor cells through the late apoptotic
pathway. Biodistribution studies in melanoma (B16F10)-bearing C57BL/6J mice
showed tumor-selective accumulation of curcumin intravenously administered via
RGDK-lipopeptide-SWNT nanovectors.
PMID- 28403561
TI - Iron deficiency anemia in chronic kidney disease: Uncertainties and cautions.
AB - Anemia in chronic kidney disease is common and iron deficiency is an important
cause. To repair iron-deficiency anemia, replacement of iron is needed. Iron can
be replaced either by the oral route or by the intravenous route. In a meta
analysis, 5 of the 6 trials were short-term, 1 to 3 months, and compared to oral
iron, the mean increase in hemoglobin with intravenous iron was only 0.31 g/dL.
However, one of the studies included in this meta-analysis was 6 months long and
had a mean decline in hemoglobin of 0.52 g/dL associated with intravenous iron
administration. Given the short duration of most of the clinical trials comparing
oral with intravenous administration of iron the long-term safety of these modes
of administration of supplemental iron could not be assessed. Replacement of iron
by the oral route is associated with mostly minor complications such as black
stools, constipation, and abdominal discomfort. In contrast, intravenous
administration of iron may lead to severe adverse events such as anaphylaxis and,
as a more recent randomized trial has suggested, delayed complications such as
infections and cardiovascular disease. Delayed complications of repeated
intravenous iron use are difficult to recognize at an individual level therefore
inpatients who have had recent cardiovascular events or are infected, intravenous
iron should probably be avoided. Balancing safety and efficacy would require
clinical judgment because 1 size may not fit all till we have better data to
support the liberal use of parenteral iron.
PMID- 28403562
TI - Feasibility, safety, and efficacy of transcatheter aortic valve replacement
without balloon predilation: A systematic review and meta-analysis.
AB - OBJECTIVES: To evaluate the feasibility, safety, and efficacy of direct
transcatheter aortic valve replacement (TAVR), that is, TAVR without balloon
predilation (BPD), by performing a systematic review and meta-analysis of
available evidence. BACKGROUND: Avoiding BPD during TAVR was shown to be feasible
in previous studies but the risks and benefits of this technique are unknown
owing to the limited number of patients included in these studies. METHODS: We
performed a systematic search for studies comparing direct TAVR vs TAVR performed
with BPD. Crude risk ratios (RRs) or mean differences and 95% confidence
intervals (CI) for each endpoint were calculated using random effects models.
RESULTS: Twenty studies including 3586 patients (1606 undergoing direct TAVR)
were selected for the analysis. Mean device success with direct TAVR was 88% with
<5% of bail-out techniques. There were no differences between direct and BPD-TAVR
in short-term (in-hospital or 30-day) mortality (RR: 1.06; 95% CI: 0.78-1.43) or
cerebrovascular events (RR: 0.92; 95% CI: 0.58-1.46). Direct TAVR associated with
reduced moderate or severe paravalvular leak post-TAVR (RR: 0.59; 95% CI: 0.36
0.98) but not with a reduced risk of permanent pacemaker implantation (RR: 0.85,
95% CI: 0.71-1.02). A slight increase in postdilation was observed in direct
transfemoral-TAVR recipients (RR: 1.2; 95% CI: 1.00-1.44). CONCLUSION: Direct
TAVR is feasible and safe. However, given the unadjusted nature of our results,
uncertainties remain regarding the independent effect of direct TAVR on outcomes
post-TAVR. Randomized studies are warranted to determine the potential benefits
of direct TAVR. (c) 2017 Wiley Periodicals, Inc.
PMID- 28403563
TI - The impact of infections on delisting patients from the liver transplantation
waiting list.
AB - Approximately 20% of the patients listed for liver transplantation die before
transplantation can be accomplished. Understanding risk factors for waiting list
mortality may help to improve survival and organ allocation. Infections are very
common in patients with cirrhosis and are associated with significant morbidity
and mortality. This study analysed the frequency and characteristics of
infections in patients awaiting liver transplantation, identified risk factors
for withdrawal from the waiting list and evaluated the impact of infections on
the clinical outcome. A retrospective analysis of consecutive patients listed for
liver transplantation in Rotterdam, the Netherlands from 2007 to 2014 was
conducted. Infections occurred in 144 of 327 studied patients (44%). In this
cohort, 23.4% of the patients on the liver transplantation waiting list were
delisted or died before transplantation. Patients with an infection were 5.2
times more likely to become delisted than noninfected patients. In the 30 days
after the first infection, patients were 33.8 times more likely to become
delisted compared to noninfected patients. High age, high MELD score, refractory
ascites and inappropriate antibiotic therapy were independent predictors for
delisting due to infection. Infections occur frequently in patients on the liver
transplantation waiting list. Emphasis on appropriate and timely antimicrobial
therapy is required.
PMID- 28403564
TI - Location of residual viable tumor cells after neoadjuvant chemotherapy: A new
concept with high prognostic performance in osteosarcoma.
AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to establish a new
concept for evaluating responses to neoadjuvant chemotherapy in osteosarcoma.
METHODS: A total of 56 high-grade extremity osteosarcoma patients were
retrospectively reviewed. A new conceptual method was derived from locations of
residual viable tumor cells (LRVTC) after chemotherapy, whether
extracompartmental or intracompartmental, rather than quantitative measurements
of necrosis rates of tumor cells. RESULTS: LRVTC after chemotherapy was
independently associated with overall survival ([OS]hazard ratio [HR] = 6.502, P
= 0.008) after adjustment for Huvos grade (HR = 3.694, P = 0.045), alkaline
phosphatase ([ALP] HR = 2.140, P = 0.226), size (HR = 0.318, P = 0.133), joint
extension (HR = 2.309, P = 0.162), and metastasis at diagnosis (HR = 8.228, P =
0.009). LRVTC was also independently associated with metastasis (HR = 5.096, P =
0.002) after adjustment for Huvos grade (HR = 2.261, P = 0.101), ALP (HR = 2.558,
P = 0.053), size (HR = 1.280, P = 0.641), and joint extension (HR = 1.800, P =
0.254). AUC values of LRVTC for OS and metastasis were superior to those of Huvos
grade: AUCs for OS (LRVTC: 0.757, Confidence Interval [CI] = 0.618 to 0.865 vs
Huvos grade: 0.590, [CI] = 0.445 to 0.725; AUC = 0.167, P = 0.086) and metastasis
(LRVTC: 0.769, CI = 0.631 to 0.874 vs Huvos grade: 0.606, [CI] = 0.461 to 0.739;
AUC = 0.163, P = 0.046). CONCLUSIONS: LRVTC after chemotherapy may be useful as a
new method with high performance for evaluating chemo-responses in osteosarcoma.
PMID- 28403565
TI - Inhibitory effect of Thymus vulgaris and Origanum vulgare essential oils on
virulence factors of phytopathogenic Pseudomonas syringae strains.
AB - Pseudomonas syringae is a phytopathogenic bacterium that causes lesions in leaves
during the colonisation process. The damage is associated with production of many
virulence factors, such as biofilm and phytotoxins. The essential oils of Thymus
vulgaris (thyme) and Origanum vulgare (oregano) have been demonstrated to inhibit
P. syringae. The aim of this study was to investigate the effects of T. vulgaris
and O. vulgare essential oils on production of virulence factors of
phytopathogenic P. syringae strains, including anti-biofilm and anti-toxins
activities. The broth microdilution method was used for determination of MIC and
biofilm inhibition assays. Coronatine, syringomycin and tabtoxin were pheno- and
genotypically evaluated. Both oils showed good inhibitory activity against P.
syringae, with MIC values from 1.43 to 11.5 mg.ml-1 for thyme and 5.8 to 11.6
mg.ml-1 for oregano. Biofilm formation, production of coronatine, syringomycin
and tabtoxin were inhibited by thyme and oregano essential oil in most strains.
The results presented here are promising, demonstrating the bactericidal activity
and reduction of virulence factor production after treatment with thyme and
oregano oil, providing insight into how they exert their antibacterial activity.
These natural products could be considered in the future for the control of
diseases caused by P. syringae.
PMID- 28403567
TI - How to Design Rating Schemes of Risk Matrices: A Sequential Updating Approach.
AB - Risk matrices have been widely used as a risk evaluation tool in many fields due
to their simplicity and intuitive nature. Designing a rating scheme, i.e.,
determining the number of ratings used in a risk matrix and assigning different
ratings to different cells, is an essential part of risk matrix construction.
However, most of the related literature has focused on applying a risk matrix to
various fields, instead of researching how to design risk matrices. Based on the
analysis of several current rules, we propose a new approach, namely, the
sequential updating approach (SUA), to design the rating scheme of a risk matrix
in a reliable way. In this article, we propose three principles and a rating
algorithm based on these principles. The three principles, namely, adjusted weak
consistency, consistent internality, and continuous screening, characterize a
good rating scheme. The resulting rating scheme has been proven to be unique. A
global rating algorithm is then proposed to create the design that satisfies the
three principles. We then explore the performance of the SUA. An illustrative
application is first given to explain the feasibility of our approach. The
sensitivity analysis shows that our method captures a resolution-reliability
tradeoff for decisionmakers in choosing an appropriate rating scheme for a risk
matrix. Finally, we compare the designs based on the SUA and Cox's axioms,
highlighting the advantages of the SUA.
PMID- 28403566
TI - Outcomes and risk stratification for late antibody-mediated rejection in
recipients of ABO-incompatible kidney transplants: a retrospective study.
AB - The required intensity of monitoring for antibody-mediated rejection (AMR) after
of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We
retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi)
kidney transplant recipients, of which 32% were also HLA incompatible (ABOi/HLAi)
with their donors. We used an adjusted negative binomial model to evaluate risk
factors for late AMR. Using this model, we risk-stratified patients into high-
and low-risk groups for the development of late AMR; 26% of patients had at least
one AMR episode; 49% of AMR episodes occurred within 30-days after transplant and
were considered early AMR. Patients with an early AMR episode had a 5.5-fold
greater incidence of developing late AMR [IRR = 5.5, (95% CI: 1.5-19.3), P =
0.01]. ABOi/HLAi recipients trended toward increased late AMR risk [IRR = 1.9,
(95% CI: 0.5-6.6), P = 0.3]. High-risk recipients (those with an early AMR or
those who were ABOi/HLAi) had a sixfold increased incidence of late AMR [IRR =
6.3, (95% CI: 1.6-24.6), P = 0.008] versus low-risk recipients. The overall
incidence of late AMR was 20.8% vs. 1.5% in low-risk recipients. Changes in anti
A/B titer did not correlate with late AMR (IRR = 0.9 per log titer increase, P =
0.7). This risk-stratification scheme uses information available within 30 days
of ABOi transplantation to determine risk for late AMR and can help direct
longitudinal follow-up for individual patients.
PMID- 28403568
TI - Preparative chiral separation and absolute configuration of the synthetic
pterocarpanquinone LQB-118.
AB - The racemic pterocarpanquinone LQB-118 is active, in mice and hamsters, against
tegumentary and visceral leishmaniasis. This compound also presents
antiinflammatory and antineoplastic activity in mice. The low level of toxicity
observed in these studies makes LQB-118 a promising drug candidate. In order to
conduct further biological testing to investigate enantioselectivity in the above
mentioned activities, a multimilligram amount of each enantiomer of LQB-118 was
produced. Furthermore, vibrational circular dichroism (VCD) and Density
Functional Theory (DFT) calculations were used to determine unambiguously their
absolute configurations. The comparison of experimental and calculated VCD data
led to the assignment of (-)-LQB-118 as 7aR,12aR and, consequently, (+)-LQB-118
as 7aS12aS.
PMID- 28403570
TI - TNF as marker of oral candidiasis, HSV infection, and mucositis onset during
chemotherapy in leukemia patients.
AB - OBJECTIVE: To assess changes in the salivary expression of IL-1alpha, IL-1beta,
IL-2, IL-6, IL-10, IL-17, and TNF in acute leukemia (AL) patients before and
during chemotherapy, and its association with HSV infection, oral candidiasis
(OC), and oral mucositis (OM) onset. METHODS: Cohort study in AL patients >15
years starting induction chemotherapy at a Mexican oncological center (2013
2014). Onset of oral lesions (OLs) was assessed during follow-up, and saliva was
obtained at baseline, at visit 2 (days 4-12), and at visit 3 (days 13-21) after
chemotherapy, treated with a protease inhibitor and stored at -70 degrees C. An
enzyme-linked immunosorbent assay was performed. Cox proportional hazards
regression models were constructed to estimate hazard ratios and its 95% CI (HR,
95% CI) for OL development. RESULTS: Forty-one patients were followed up, and 17
(41.5%) developed OLs. OL patients had higher baseline salivary IL-1alpha than
those without lesions (p = 0.040). During visit 2, OL patients had higher levels
of IL-1alpha (p = 0.033), IL-1beta (p = 0.016), IL-6 (p = 0.035), and TNF (p =
0.019) than those who did not develop OLs. Patients with HSV infection, OC, and
OM showed higher salivary TNF levels during follow-up (HR: 3.52, 95% CI: 1.35
9.14, p = 0.010). CONCLUSION: AL patients undergoing chemotherapy with high
salivary TNF levels were more likely to develop HSV infection, OC, and OM.
PMID- 28403569
TI - Assessment of a short hypnosis in a paediatric operating room in reducing
postoperative pain and anxiety: A randomised study.
AB - AIMS AND OBJECTIVES: To assess the impact of a short hypnotic session on
postoperative anxiety and pain in major orthopaedic surgery. BACKGROUND: Despite
specific information given before a scheduled paediatric surgery, perioperative
anxiety can become important. DESIGN: Randomised Clinical Study. METHODS: The
study is an open single-centre randomised clinical study comparing a "control"
group versus a "hypnosis" group receiving a short hypnosis pre-induction session
as additional experimental analgesic procedure. The primary endpoint was the
postoperative anxiety, blindly assessed using a visual analogue scale. RESULTS:
The study involved 120 children (age 10-18 years). The results showed no
difference between control group versus hypnosis group. Twenty-four hours after
surgery (Day+1), the patient's anxiety score was not different between control
and hypnosis groups (median [Q1-Q3]: 1 [0; 3] vs. 0 [0; 3], respectively, p =
.17). Each group experienced a significant decrease in anxiety level between the
day before surgery (Day-1) and the day after surgery (Day+1) (median ([Q1-Q3])
difference of the anxiety score: 2 [4; 0] and 2 [4; 0], respectively, p < .0001
in each group). The postoperative pain scores were low and not different between
groups (median [Q1-Q3]: 2 [0; 3] in control group vs. 3 [1; 3] in hypnosis group,
p = .57). CONCLUSION: This randomised study on a short hypnosis session performed
in the operating room prior to a major surgery showed no difference in
postoperative anxiety and pain levels. The decrease in anxiety and pain levels
may be due to the addition of nurse pre-operative interviews and optimisation in
communication in the operating room. RELEVANCE TO CLINICAL PRACTICE: As
postoperative anxiety level was low in both control and hypnosis groups, nurse
pre-operative interviews and nurse training in hypnosis may contribute to the
optimisation of global management and decrease the postoperative anxiety level.
PMID- 28403571
TI - Novel autoantibody against the beta2-glycoprotein I/human leucocyte antigen-DR
complex in patients with refractory cutaneous ulcers.
PMID- 28403572
TI - Development and Application of a Probabilistic Risk-Benefit Assessment Model for
Infant Feeding Integrating Microbiological, Nutritional, and Chemical Components.
AB - A probabilistic and interdisciplinary risk-benefit assessment (RBA) model
integrating microbiological, nutritional, and chemical components was developed
for infant milk, with the objective of predicting the health impact of different
scenarios of consumption. Infant feeding is a particular concern of interest in
RBA as breast milk and powder infant formula have both been associated with risks
and benefits related to chemicals, bacteria, and nutrients, hence the model
considers these three facets. Cronobacter sakazakii, dioxin-like polychlorinated
biphenyls (dl-PCB), and docosahexaenoic acid (DHA) were three risk/benefit
factors selected as key issues in microbiology, chemistry, and nutrition,
respectively. The present model was probabilistic with variability and
uncertainty separated using a second-order Monte Carlo simulation process. In
this study, advantages and limitations of undertaking probabilistic and
interdisciplinary RBA are discussed. In particular, the probabilistic technique
was found to be powerful in dealing with missing data and to translate
assumptions into quantitative inputs while taking uncertainty into account. In
addition, separation of variability and uncertainty strengthened the
interpretation of the model outputs by enabling better consideration and
distinction of natural heterogeneity from lack of knowledge. Interdisciplinary
RBA is necessary to give more structured conclusions and avoid contradictory
messages to policymakers and also to consumers, leading to more decisive food
recommendations. This assessment provides a conceptual development of the RBA
methodology and is a robust basis on which to build upon.
PMID- 28403573
TI - Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report
of 3 challenging cases.
AB - Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors
(MPNST) reveal histological and immunohistochemical similarities, including S100
positivity and negative staining for conventional melanocytic markers. We present
3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in
which first findings led to initial misdiagnoses as cutaneous MPNST and benign
peripheral sheath nerve tumor (neurofibroma). The identification of adjacent
atypical melanocytic hyperplasia in the overlying skin along with tumor cell
proliferation, also in the superficial dermis, the neurotropic component and the
absence of any relationship between the tumor and a major nerve, pre-existing
neural benign tumor or the existence of stigmata suggestive of neurofibromatosis
raised consideration of a DM. Careful attention should be paid to the presence of
a firm dermal nodule and atypical scar lesions especially in sun-exposed areas
(mainly head and neck region) in elderly patients associated with S100-positive
spindle cell proliferation, solar elastosis and adjacent atypical melanocytic
proliferation. In such cases, the possibility of a DM should be excluded with
caution, especially if the tumor reveals a paucicellular morphology resembling
various non-melanocytic neoplasms including malignant or benign peripheral sheath
nerve tumors.
PMID- 28403574
TI - Determination of artemisitene in rat plasma by ultra-performance liquid
chromatography/tandem mass spectrometry and its application in pharmacokinetics.
AB - RATIONALE: Artemisitene shows a wide variety of pharmacological activities, such
as antioxidant protection in vitro and in vivo. It has been identified as a novel
Nrf2 inducer. However, there is no report on an ultra-performance liquid
chromatography/tandem mass spectrometry (UPLC/MS/MS) method to quantitate
artemisitene in rat plasma and its application to a pharmacokinetic profile
study. METHODS: An ACQUITY UPLCTM BEH Symmetry Shield RP18 column (1.7 MUm, 2.1
mm * 100 mm) was used at a flow rate of 0.3 mL.min-1 . Mass detection was
performed by electrospray ionization tandem mass spectrometry via multiple
reaction monitoring (MRM) in positive mode. Plasma samples were pre-treated by a
single-step extraction with 0.1% formic acid aqueous solutions-acetonitrile, and
tolbutamide was used as internal standard. RESULTS: The calibration curve was
from 0.98 to 1000 ng?mL-1 (r2 = 0.995). The extraction recoveries were 61.5
79.4% and 81.7-94.6% for artemisitene and tolbutamide, respectively. The lower
limit of quantification (LLOQ) was 0.98 ng?mL-1 . The absolute bioavailability of
artemisitene was 3.7% after intravenous and oral administration in rats.
CONCLUSIONS: The UPLC/MS/MS assay was validated for linearity, accuracy,
stability, extraction recovery, matrix effects, and intra-day and inter-day
precision. The method, for the first time, achieved some pharmacokinetic
parameters and was successfully applied to a pharmacokinetic study Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28403575
TI - Comparison of two equivalent model for end-stage liver disease scores for
hepatocellular carcinoma patients using data from the United Network for Organ
Sharing liver transplant waiting list registry.
AB - Patients with hepatocellular carcinoma (HCC) have been advantaged on the liver
transplant waiting list within the United States, and a 6-month delay and
exception point cap have recently been implemented to address this disparity. An
alternative approach to prioritization is an HCC-specific scoring model such as
the MELD Equivalent (MELDEQ ) and the mixed new deMELD. Using data on adult
patients added to the UNOS waitlist between 30 September 2009 and 30 June 2014,
we compared projected dropout and transplant probabilities for patients with HCC
under these two models. Both scores matched actual non-HCC dropout in groups with
scores <22 and improved equity with non-HCC transplant probabilities overall.
However, neither score matched non-HCC dropout accurately for scores of 25-40 and
projected dropout increased beyond non-HCC probabilities for scores <16. The main
differences between the two scores were as follows: (i) the MELDEQ assigns 6.85
more points after 6 months on the waitlist and (ii) the deMELD gives greater
weight to tumor size and laboratory MELD. Post-transplant survival was lower for
patients with scores in the 22-30 range compared with those with scores <16 (P =
0.007, MELDEQ ; P = 0.015, deMELD). While both scores result in better equity of
waitlist outcomes compared with scheduled progression, continued development and
calibration is recommended.
PMID- 28403576
TI - No Pharmacokinetic Drug-Drug Interaction Between Prasugrel and Vorapaxar
Following Multiple-Dose Administration in Healthy Volunteers.
AB - Vorapaxar is a first-in-class antagonist of the protease-activated receptor-1,
the primary thrombin receptor on human platelets, which mediates the downstream
effects of thrombin in hemostasis and thrombosis. Prasugrel is a platelet
inhibitor that acts as a P2Y12 receptor antagonist through an active metabolite,
R-138727. This study investigated the interaction of these 2 platelet antagonists
when coadministered. This was a randomized, open-label, multiple-dose study in 54
healthy volunteers consisting of a fixed-sequence crossover and a parallel group
design. In sequence 1, 36 subjects received prasugrel 60 mg on day 1 and then
prasugrel 10 mg once daily on days 2 to 7, followed by vorapaxar 40 mg and
prasugrel 10 mg on day 8 and then vorapaxar 2.5 mg and prasugrel 10 mg orally
once daily on days 9 to 28. In sequence 2, 18 subjects received vorapaxar 40 mg
on day 1 and then vorapaxar 2.5 mg once daily on days 2 to 21. The geometric mean
ratios (90% confidence intervals) for AUCtau and Cmax of
coadministration/monotherapy for vorapaxar (0.93 ng.h/mL[0.85-1.02 ng.h/mL] and
0.95 ng/mL [0.86-1.05 ng/mL]) and R-138727 (0.91 ng.h/mL [0.85- 0.99 ng.h/mL] and
1.02 ng/mL [0.89-1.17 ng/mL]) were within prespecified bounds, demonstrating the
absence of a pharmacokinetic interaction between vorapaxar and prasugrel. There
was no specific safety or tolerability risk associated with multiple-dose
coadministration of vorapaxar and prasugrel. In conclusion, in this study in
healthy volunteers, there was no pharmacokinetic drug-drug interaction between
vorapaxar and prasugrel. Multiple-dose coadministration of the 2 drugs was
generally well tolerated.
PMID- 28403577
TI - Battle-axe fold: surgical technique for in-the-bag implantation of an artificial
iris implant.
PMID- 28403578
TI - Correction: Dehydroandrographolide, an iNOS inhibitor, extracted from
Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer
cells.
PMID- 28403579
TI - Correction: Pinin interacts with C-terminal binding proteins for RNA alternative
splicing and epithelial cell identity of human ovarian cancer cells.
PMID- 28403580
TI - Correction: Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a
candidate immunotherapeutic target for uterine tumors.
PMID- 28403581
TI - Correction: miR-509-3p is clinically significant and strongly attenuates cellular
migration and multi-cellular spheroids in ovarian cancer.
PMID- 28403582
TI - Effects of Post-Deposition Annealing on ZrO2/n-GaN MOS Capacitors with H2O and O3
as the Oxidizers.
AB - GaN-based metal-oxide-semiconductor capacitors with ZrO2 as the dielectric layer
have been prepared by atomic layer deposition. The accumulation and depletion
regions can be clearly distinguished when the voltage was swept from -4 to 4 V.
Post-annealing results suggested that the capacitance in accumulation region went
up gradually as the annealing temperature increased from 300 to 500 degrees C. A
minimum leakage current density of 3 * 10-9 A/cm2 at 1 V was obtained when O3 was
used for the growth of ZrO2. Leakage analysis revealed that Schottky emission and
Fowler-Nordheim tunneling were the main leakage mechanisms.
PMID- 28403583
TI - Control of the Singlet-Triplet Energy Gap in a Thermally Activated Delayed
Fluorescence Emitter by Using a Polar Host Matrix.
AB - The photoluminescence properties of a thermally activated delayed fluorescence
emitter, 1,2-bis(carbazol-9-yl)-4,5-dicyanobenzene (2CzPN), doped in a host
matrix consisting of 1,3-bis(9-carbazolyl)benzene and a polar inert molecule,
camphoric anhydride (CA), in various concentrations have been investigated. It is
found that the addition of CA stabilizes only the lowest singlet excited state
(S1) of 2CzPN without changing the energy level of the lowest triplet excited
state (T1), leading to a reduction in the energy gap between S1 and T1. The
maximum reduction of energy gap achieved in this work has been determined to be
around 65 meV from the shift of the fluorescence spectrum and the temperature
dependence of the photoluminescence decay rate.
PMID- 28403585
TI - The role of nutraceuticals and phytotherapy in the management of urinary tract
infections: What we need to know?
AB - Urinary Tract Infections (UTIs) are amongst the most common infectious diseases
and carry a significant impact on patient quality of life and health care costs.
Despite that, there is no well-established recommendation for a "standard"
prophylactic antibiotic management to prevent UTI recurrences. The majority of
patients undergoes long-term antibiotic treatment that severely impairs the
normal microbiota and increases the risk of development of multidrugresistant
microorganisms. In this scenario, the use of phytotherapy to both alleviate
symptoms related to UTI and decrease the rate of symptomatic recurrences is an
attractive alternative. Several recently published papers report conflicting
findings and cannot give confident recommendations for the everyday clinical
practice. A new approach to the management of patients with recurrent UTI might
be to use nutraceuticals or phytotherapy after an accurate assessment of the
patient's risk factors. No single compound or mixture has been identified so far
as the best preventive approach in patients with recurrent UTI. We reviewed our
non-antibiotic approach to the management of recurrent UTI patients in order to
clarify the evidence-base for the commonly used substances, understand their
pharmacokinetics and pharmacodynamics in order to tailor the best way to improve
patient's quality of life and reduce the rate of antibiotic resistance. Lack of a
gold-standard recommendation and the risk of increasing antibiotic resistance is
the reason why we need alternatives to antibiotics in the management of urinary
tract infections (UTIs). A tailored approach according to bacterial
characteristics and the patient risk factors profile is a promising option.
PMID- 28403586
TI - Urethroplasty with dorsal buccal mucosa graft. Is it still the method of choice
in long term urethral stenosis?
AB - The aim of our work was to evaluate the long-term changes in symptoms (median 42
months) and to analyze data for any negative predictive factors for the
application of the procedure, in patients who underwent to urethroplasty with
dorsal buccal mucosa graft. During the period from 2010 to 2015 27 patients were
examined. Than they underwent urethroplasty using dorsal buccal mucosa graft
(graft of 4 x 2.5 cm). The evaluation of symptoms has been addressed through the
application of the IPSS Quality of Life Questionnaire (International Prostatic
Symptoms Score) and the evaluation of urinary flow has been carried out by a
comparative analysis between the pre- and post-operative uroflowmetry. As our
study has shown, data obtained by the screening tests in the post-operative
follow-up indicate that there is an increase in the maximum flow of urine until 1
month after surgery. The results in the long-term follow-up are different because
they show a partial reduction of the maximum flow although it is maintained
around an average value of 23 ml/s being still higher than the maximum flow in
the pre-operative period. According to our results it follows that there is a low
failure rate of the procedure after a median of 42 months. Only in patients with
urethral stenosis longer than 2 cm, a lower long term success is achieved. From
what we could observe, this length of the stenosis seems to be the only negative
predictive factor for long-term maintenance of a good Quality of Life in patients
undergoing the procedure. The results obtained from our study confirm literature
data according to which, the gold standard for 2-cm long bulbar urethral
stricture whose lumen is well preserved with circumferential spongiofibrosis
limited to 1-2 mm is the dorsal graft urethroplasty with buccal mucosa that in
our study showed success rates higher of 80% after a median follow up of 42
months and a percentage of relapse-free patients of 82.1% ( median 3.5 years).
PMID- 28403587
TI - Tadalafil once daily: Narrative review of a treatment option for female sexual
dysfunctions (FSD) in midlife and older women.
AB - Female Sexual Disorders (FSD) include a complex, multidimensional, individual
experience that can change as an individual age, suggesting that these problems
are caused by multiple factors including psychosocial factors, personal
relationships, pathologic changes caused by diseases, and pharmacologic
influences. Menopause is an important time for middle aged women and
postmenopausal physiological changes could have a significant role in the
development of FSD. Few is still known about their correct definition and
treatment. Their incidence, prevalence and risk factors are difficult to define
because of a high level of overlap in the experience of problems with desire,
arousal, and orgasm. Little evidences are known about the best therapeutic
approach, and both non-pharmacological and pharmacological treatment options have
been described. Among these, phosphodiesterase type 5 inhibitors could be an
effective option for many subtypes of female sexual disorders, with an
improvement in different aspects of sexual function, such as desire, arousal,
orgasm and sexual satisfaction. In this paper authors reviewed what is already
known about the use of these vasoactive agents, particularly tadalafil, as a
treatment option for female sexual disturbances.
PMID- 28403588
TI - Daidzein plus isolase associated with zinc improves clinical symptoms and quality
of life in patients with LUTS due to benign prostatic hyperplasia: Results from a
phase I-II study.
AB - OBJECTIVE: In the last years there is a growing interest in nutraceutical
substances that seems able to improve clinical symptoms in patients with lower
urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). In this
paper, we evaluated both efficacy and safety of a combination of daidzein with
isolase and zinc in patients with LUTS due to BPH. MATERIALS AND METHODS: In a
phase I-II study clinical trial we enrolled patients with clinical and
instrumental diagnosis of LUTS associated to BPH that received a six-month
treatment with a combination of daidzein with isolase and zinc (1 tablet/day).
Clinical, laboratory and instrumental analyses were carried out at the time of
admission (T0) and 6 months after the ending of the treatment (T1). The Italian
version of International Prostatic Symptom Score (IPSS), International Index of
Erectile Function (IIEF-5) and Quality of Well-Being (QoL) questionnaires were
used. The development of adverse drug reactions (ADRs) and drug interactions
(DDIs) were recorded using the Naranjo scale and drug interaction probability
scale. Student's t test and Anova test were used for statistical analysis, and
the threshold of statistical significance was set at P < 0.05. RESULTS: We
enrolled 71 patients, 62 (87.3%) completed the follow-up and we documented a
significant differences between T0 and T1 in terms of IPSS [21.5 +/- 1.2 vs 16.2
+/- 1.5; (-4.8); p < 0.001], Cmax [9.7 +/- 3.7 vs 15.3 +/- 2.5; (+5.6); p <
0.001] and QoL [0.56 +/- 0.15 vs 0.84 +/- 0.19; (+0.28); p < 0.001]. In contrast,
no significant difference were recorded in terms of IIEF-5 [p = 0.50] and PSA [p
= 0.67]. Finally, we did not record any significant ADRs or DDIs during the
study. CONCLUSIONS: In this study, we documented that a combination of daidzein
with isolase and zinc, reduces the clinical symptoms of LUTS and improves the
quality of life in patients with BPH, without the development of ADRs or DDIs.
PMID- 28403589
TI - The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in
patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized
clinical trial.
AB - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a
complex condition, characterized by uncertain etiology and by limited response to
therapy. The definition of CP/CPPS includes genitourinary pain with or without
voiding symptoms in the absence of uropathogenic bacteria, as detected by
standard microbiological methods, or another identifiable cause such as
malignancy. The efficacy of various medical therapies, has been evaluated in
clinical studies, but evidence is lacking or conflicting. We compared Serenoa
Repens in monotherapy versus Palmitoylethanolamide (PEA) in combination with
Alpha-lipoic acid (ALA) and evaluated the efficacy of these treatments in
patients with CP/CPPS. METHODS: We conducted a randomized, single-blind trial. 44
patients diagnosed with CP/CPPS (mean age 41.32 +/- 1.686 years) were randomly
assigned to treatment with Palmitoylethanolamide 300 mg plus Alpha-lipoic acid
300 mg (Peanase(r)), or Serenoa Repens at 320 mg. Three questionnaires (NIH-CPSI,
IPSS and IIEF5) were administered at baseline and after 12 weeks of treatment in
each group. RESULTS: 12 week treatment with Peanase significantly improved the
IPSS score compared to the same period of treatment with Serenoa Repens, and
significantly reduced NIH-CPSI score. Similar results were observed in the
different NIH-CPSI subscores break down. However, the same treatment did not
result in significant improvement of the IIEF5 score. Both treatments did not
produce undesired effects. CONCLUSIONS: The present results document the efficacy
of an association of Palmitoylethanolamide (PEA) and Alpha-lipoic acid (ALA)
administered for 12 weeks for treating patients with CP/CPPS, compared with
Serenoa Repens monotherapy.
PMID- 28403590
TI - Efficacy of pollen extract in association with group B vitamins for pain relief
in chronic prostatitis/chronic pelvic pain syndrome: A survey of urologists'
knowledge about its clinical application.
AB - INTRODUCTION AND AIM OF THE STUDY: Chronic prostatitis/chronic pelvic pain
syndrome (CP/CPSS) is a pathology of high prevalence in Italian male population,
difficult to diagnose and to treat and with poor response to conventional
therapy. Aim of this study was to review the evidence of the literature about the
therapeutic effects of a plant product containing flower pollen extracts and
group B vitamins on symptoms resolution and amelioration of CP/CPPS patients'
quality of life and to investigate the knowledge among practicing urologists
about the clinical application of this product. MATERIALS AND METHODS: A group of
38 urologists was submitted to an investigational survey of the knowledge of the
clinical applications of a plant product containing flower pollen extracts and
group B vitamins Results: 71% of the urologists interviewed prescribed the plant
product for CBP and CP/CPPS at least one time in a month and 11% prescribed it
more than 5 times; 67% had evidence of clear ameliorations in pain relief and on
patient's quality of life and 47% reported that the effectiveness is comparable
to NSAIDs; 39% also reported a significant effect for the improvement of the
urinary symptoms of patients. No gastric or general side effects have been
noticed during the administration period of this plant product. Finally, the cost
of the product has always reported to be sustainable for the patients.
CONCLUSIONS: From the results of this investigational survey, we can state that
the plant product containing flower pollen extracts and group B vitamins is well
known and demonstrated beneficial effects on symptoms resolution and amelioration
of quality of life in patients with chronic prostatitis/chronic pelvic pain
syndrome.
PMID- 28403591
TI - Comparison of the clinical parameters of benign prostate hyperplasia in diabetic
and non diabetic patients.
AB - OBJECTIVE: We evaluated the correlation between benign prostate hyperplasia (BPH)
measures and diabetes mellitus in men with benign prostate hyperplasia in a
prospective study. MATERIALS AND METHODS: Between 2008-2012, 100 diabetic and 200
non diabetic patients undergoing surgery due to benign prostate hyperplasia were
enrolled in the study. The parameters evaluated for each patients included
prostate volume, fasting blood glucose, HbA1c, total testosterone, total
prostatic specific antigen (T-PSA), triglicerides, total cholesterol and body
mass index (BMI). A questionnaire including international prostate symptom score
(IPSS) was sdministered and uroflow test measuring the peak urinary flow rate was
performed to appreciate the complaints of the patients objectively. RESULTS:
Diabetic patients are more likely to have larger prostate volume. The symptom
score evaluated by IPSS and post micturition residual volume were also
significantly higher in diabetic groups. The other statistically significant
different parameter between two groups was total testosterone that diabetic
patients tend to have lower levels. Diabetic counterparts were established to
have higher BMI. No statistically significant differentiation was observed about
trigliceryde and total cholesterol levels and uroflow rates. CONCLUSIONS: Our
study suggests a positive correlation between high prostate volume and diagnosis
of diabetes mellitus in patients with benign prostatic hyperplasia. We also
observed a positive correlation between symptom scores and post micturion
residual volumes and diagnosis of diabetes mellitus suggesting that the presence
of diabetes is related to both static and dynamic components of benign prostate
hyperplasia. Additionally testosterone levels were lower in diabetic patients.
Further studies need to confirm these relationship in a larger population.
PMID- 28403592
TI - Comparison of transurethral incision of the prostate and silodosin in patients
having benign prostatic obstruction in terms of retrograde ejaculation.
AB - BACKGROUND: To compare the functional outcomes and retrograde ejaculation (RE)
after transurethral incision of the prostate (TUIP) or silodosin in bladder
outlet obstruction (BOO) secondary to a small prostate. METHODS: Prospectively
collected data from December 2011 through December 2014 of 192 LUTS patients
having fertility concerns with prostate volume smaller than 40 ml receiving
either TUIP or silodosin treatment were prospectively reviewed. The treatment
outcomes were evaluated and compared. RESULTS: TUIP was performed in 96 cases and
silodosin 8 mg was prescribed in 96 cases. At 12th months after TUIP or
continuous silodosin treatment, the decrease in mean International Prostate
Symptom Score (IPSS) and postvoiding residual urine (PVR) and the improvement of
mean maximal flow rate (Qmax) were significant (p = 0.000). The improvement in
IPPS and Qmax was significantly higher in TUIP group compared to silodosin group
(p = 0.005, p = 0.000) with a lower rate of retrograde ejaculation (RE) in TUIP
group. (11/96 vs 33/96) (p = 0.000) Conclusions: Both TUIP and silodosin ensures
comparable improvement in PVR, IPSS and Qmax with a lower rate of RE on the TUIP
group in prostates weighing less than 40 grams suggesting that TUIP is a better
choice in younger patiens seeking preservation of ejaculation with fertility
concerns.
PMID- 28403593
TI - Influence of secondary diagnoses in the development of urinary incontinence after
radical prostatectomy.
AB - OBJECTIVE: To study whether there are factors related to secondary diagnoses
(SDg) present in patients with prostate cancer that influence the development of
urinary incontinence after radical prostatectomy (RP). MATERIALS AND METHODS: A
retrospective multicenter observational study was performed reviewing the medical
records of 430 men who underwent RP due to organ-confined prostate cancer in 9
different hospitals. Two study groups were distinguished: Group A (GA): Patients
without urinary incontinence after RP; Group B (GB): patients with any degree of
post-surgical urinary incontinence. RESULTS: Average age at surgery was 63.42
years (range 45-73). 258 patients were continent after surgery and 172 patients
complaint of any degree of incontinence after RP. A higher percentage of healthy
patients was found in group A (continent after surgery) than in group B (p =
0.001). The most common SDg prior to surgery were hypertension, lower urinary
tract symptoms, dyslipidemia, diabetes mellitus and erectile dysfunction, but
none did show a greater trend towards post-surgical incontinence. CONCLUSIONS: A
better health status prior to surgery is associated to a lower incidence of new
onset urinary incontinence after radical prostatectomy. However, no correlation
was found between the most common medical disorders and the development of post
surgical urinary incontinence.
PMID- 28403594
TI - The effect of surgical technique on hemodynamics, arterial oxygenation and
pulmonary mechanics in radical prostatectomy operations.
AB - OBJECTIVE: The effects of surgical technique on respiratory mechanics, arterial
oxygenation and hemodynamics in radical prostatectomy operation were
investigated. METHODS: The study was planned on ASA II-III, 40-65 years old,
fourty patients scheduled for radical prostatectomy under general anesthesia.
They were divided into two groups: perineal and suprapubic (Group P, n = 20;
Group S, n = 20). Heart rate, mean arterial blood pressure, arterial oxygen
saturation (SpO2), partial pressure of end-tidal carbon dioxide (PEtCO2), Peak
inspiratory pressure (PIP), plato pressure (Pplato), partial pressure of oxygen
in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood
(PaCO2) values were evaluated at 10 minutes after induction. After the position
applied for surgery in the 30.60 and 90th minutes, the Alveolar-arterial oxygen
pressure gradient (P(A-a) O2), the ratio of physiologic dead space over tidal
volume (VD/VT), arterial to end tidal CO2 gradient (P(a-et) CO2), static
compliance (CS), dynamic compliance (CD) were assessed. RESULTS: In the
assessment of groups, there were not statistical differences about mean blood
pressure, heart rate, SpO2, PetCO2, PaO2, plateau pressure, and P (A-a) values (p
> 0.05). Peak inspiratory pressure was higher in Group P. Peak inspiratory
pressure and plateau pressure increased with CO2 insufflation in Group P. PaCO2
and P(a-et) CO2 were higher statistically significantly in Group 0. There was no
difference in terms of the PetCO2 values. VD/VT ratios were statistically
significantly lower in the Group P. CONCLUSIONS: Suprapubic surgery was shown to
improve oxygenation and respiratory mechanics without causing any hemodynamic
side effect in radical prostatectomy operation.
PMID- 28403595
TI - Factors affecting surgical margin positivity in robotic assisted radical
prostatectomy.
AB - OBJECTIVES: After radical prostatectomy, surgical margin positivity is an
important indicator of biochemical recurrence and progression. In our study we
want to compare the surgical margin positivity rates for retropubic radical
prostatectomy (RRP) and robotic assisted radical prostatectomy (RALP) and
investigate the factors affecting surgical margin positivity in RALP. MATERIALS
AND METHODS: Data from 78 RRP and 62 RALP patients operated from 2011 May to 2016
March were retrospectively screened. Patients in both groups were compared in
terms of age, postop hematocrit reduction, hospital stay, duration of follow-up,
surgical margin positivity, biochemical recurrence and oncologic parameters. In
RALP group it was searched the relationship between the surgical margin
positivity and prostate specific antigen (PSA), positive biopsy core, biopsy
Gleason scoring, pathologic stage and Gleason scoring, lymph node positivity,
lymphovascular and perineural invasion, extracapsular extension, seminal vesicle
invasion, prostate weight. RESULTS: Patients in the RALP group had lower postop
hematocrit reduction and shorter hospital stay (p < 0.001). There was no
difference in surgical margin positivity between RALP and RRP groups (37.1% vs.
29.5%, p = 0.341). In RALP group there was a correlation between surgical margin
positivity and positive biopsy core number (p = 0.011), pathologic stage (p <
0.001) and Gleason score (p < 0.001), EAU risk classification (p = 0.001),
seminal vesicle invasion (p = 0.045), extraprostatic extension (p < 0.001). There
was no correlation between prostate weight (p = 0.896), PSA (p = 0.220), biopsy
Gleason score (p = 0.266), lymph node positivity (p = 0.140), perineural (p =
0.103) and lymphovascular invasion (p = 0.92) with surgical margin positivity.
CONCLUSIONS: Positive biopsy core number, pathological stage and Gleason score,
EAU risk classification, seminal vesicle invasion and extraprostatic extension
are correlated with surgical margin positivity in RALP.
PMID- 28403596
TI - Blue light cystoscopy with hexylaminolevulinate: Our 7 years experience.
AB - AIM: The objective of the present study is to evaluate the diagnostic accuracy of
hexylaminolevulinate (HAL) blue light cystoscopy compared with standard white
light cystoscopy (WLC) in daily practice. MATERIALS AND METHODS: An
observational, comparative, controlled (within patient) study was carried out at
our Center. 61 consecutive patients with suspected or confirmed bladder cancer
were recruited for the study from January 2008 until January 2015. Patients with
suspected bladder cancer (positive cytology with negative WLC) or history of
previous high-grade NMIBC or CIS were included in the study. Biopsies/resection
of each positive lesion/suspicious areas were always taken after the bladder was
inspected under WLC and BLC. Diagnoses of bladder tumor or CIS were considered as
positive results, and the presence of normal urothelium in the biopsy specimen as
negative result. RESULTS: 61 BLC were performed. 15/61 (24.5%) with suspected
initial diagnosis of NMIBC and 46/61 (75.5%) with a history of high-risk non
muscle invasive bladder cancer (NMIBC). We performed a total of 173
biopsies/TURBT of suspicious areas: 129 positive only to the BLC and 44 both
positive to WLC and BLC. 84/173 biopsies/TURBT were positive for cancer. All 84
NMIBC were positive to the BLC, while 35/84 were positive to the WLC with a
sensitivity of BLC and WLC respectively of 100% and 41.7%. Sensitivity of WLC for
highgrade NMIBC and CIS was 34.1% and 39% respectively while sensitivity of BLC
for high-grade NMIBC and CIS was 100%. The specificity of the WLC was 79.9%
compared to 48.5% of the BLC. The positive predictive value of BLC and WLC were
respectively 48% (95% CI: 0.447-0.523) and 79% (95% CI: 0.856-0.734).
CONCLUSIONS: Our data confirm those reported in the literature: BLC increases the
detection rate of NMIBC particularly in high risk patients (history of CIS or
high grade). BLC is a powerful diagnostic tool in the diagnosis of bladder cancer
if malignancy is suspected (positive urine cytology) and if conventional WLC is
negative.
PMID- 28403597
TI - A retrospective comparison between transrectal and transperineal prostate biopsy
in the detection of prostate cancer.
AB - BACKGROUND: The aim of this study was to analyze the differences between
TRUSguided transrectal prostate biopsy (TR) and transperineal prostate biopsy
(TP) in the diagnosis of prostate cancer. The two biopsy methods were evaluated
in terms of diagnostic sensitivity and of early and late complications. METHODS:
This retrospective study was realized through the review of clinical records of
219 men that received a prostate biopsy between 2004 and 2014. The biopsy was
performed because of elevated prostate-specific antigen (PSA), abnormal digital
rectal examination findings (DRE), abnormal transrectal ultrasound (TRUS)
findings and symptoms due to prostate diseases. The cohort study was subdivided
in two groups: 108 patients received a transrectal biopsy between 2004 and 2006
and 111 received a transperineal biopsy between 2007 and 2014. In both groups,
first biopsy was performed with 12 cores scheme whereas second or third biopsy
were performed with 18 cores scheme; in this study we excluded patients who
underwent to biopsies with different number cores to reduce the bias. Both groups
were evaluated on the basis of age, total PSA, PSA ratio (F/T), DRE/TRUS
findings, presence/absence of low urinary tracts symptoms (LUTS),
presence/absence of benign prostatic hyperplasia (BPH), histologic findings of
biopsy cores and immediate/postoperative complications. Then, it was evaluated
the overall cancer detection rate and the stratified cancer rate on the basis of
the previous reported parameters. Finally, we analyzed the early and late
complication rate in both groups. U Mann-Whitney test was used to evaluate the
quantitative variables and chi2-test or Fisher exact test for qualitative
variables. p < 0.05 was considered statistically significant. RESULTS: 66 cancers
were detected in 219 patients of the study; 29 cancers were detected in the TP
group and 37 in the TR group. There were no statistically significant differences
in the overall cancer rate detected in both groups (26.13% e 34.26% respectively;
p = 0.190). However, TP biopsy detected more cancers at first biopsy than TR
biopsy (89.7% vs 78.4% respectively; p = 0.021). Moreover, TP biopsy detected
more cancers in those patients with low cancer suspect (PSA < 4 ng/ml, F/T > 15%,
negative TRUS), instead TR biopsy had more sensitivity in detecting cancer in
those patients with high cancer suspect (PSA > 10 ng/ml, F/T < 15%, TRUS with
abnormal lesions). The presence of BPH did not influence sensitivity in both
cases. There were no significant differences in the early complication rate
whereas a statistically significant difference was observed in the late
complication rate (4% vs 11% in TP and TR biopsy, respectively; p = 0.019).
CONCLUSIONS: No statistically significant differences in sensitivity were
observed between TP and TR biopsy, but TP biopsy detected more cancers at first
time biopsy. Complications rate was lower in the TP group. Therefore, we conclude
that the Urologist has the final choice in deciding the most appropriate biopsy
technique, considering sensitivity and complications.
PMID- 28403598
TI - Prospective study to compare antibiosis versus the association of N
acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing
urinary tract infections in patients submitted to urodynamic investigation.
AB - BACKGROUND: The abuse of antimicrobical drugs has increased the resistance of
microorganisms to treatments, thus to make urinary tract infections (UTIs) more
difficult to eradicate. Among natural substances used to prevent UTI, literature
has provided preliminary data of the beneficial effects of D-mannose, N
acetylcysteine, and Morinda citrifolia fruit extract, due to their complementary
mechanism of action which contributes respectively to limit bacteria adhesion to
the urothelium, to destroy bacterial pathogenic biofilm, and to the anti
inflammatory and analgesic activity. The purpose of this study was to compare the
administration of an association of D-mannose, N-acetylcysteine (NAC) and Morinda
citrifolia extract versus antibiotic therapy in the prophylaxis of UTIs
potentially associated with urological mini-invasive diagnostics procedures, in
clinical model of the urodynamic investigation. METHODS: 80 patients eligible for
urodynamic examination, 42 men and 38 women, have been prospectively enrolled in
the study and randomised in two groups (A and B) of 40 individuals. Patients of
group A followed antibiotic therapy with Prulifloxacine, by mouth 400 mg/day for
5 days, while patients of the group B followed the association of mannose and NAC
therapy, two vials/day for 7 days. Ten days after the urodynamic study, the
patients were submitted to urine examination and urine culture. RESULTS: The
follow up assessment didn't show statistical significant difference between the
two groups regarding the incidence of UTI. CONCLUSIONS: The association of
mannose and NAC therapy resulted similar to the antibiotic therapy in preventing
UTIs in patients submitted to urodynamic examination. This result leads to
consider the possible use of these nutraceutical agents as a good alternative in
the prophylaxis of the UTI afterwards urological procedures in urodynamics.
PMID- 28403599
TI - Renal extracapsular hypoechoic rim and kidney cortical thickness.
AB - OBJECTIVES: A renal extracapsular hypoechoic rim was previously recognized and
interpreted as a typical sonographic finding of renal failure. Subsequently it
was hypothesized that the hypoechoic rim could be produced by a state of sodium
retention and oedema caused by nephropathy but not necessarily associated with
renal failure. In order to get this cleared we performed a retrospective analysis
of 80 renal ultrasound examinations, carried out at our center, in 41 of which it
was found a renal extracapsular hypoechoic rim. MATERIALS AND METHODS: For each
patient we recorded the glomerular filtration rate, the diameters in the
longitudinal axis, the resistive indexes and the cortical thickness of each
kidney, the possible presence and thickness of the hypoechoic rim and yet the
possible coexistence of diabetes mellitus, proteinuria and clinical signs of
fluid overload as peripheral oedema, distended jugular veins, ascites, increased
caliber and reduced respiratory excursion of the vena cava. RESULTS: The F value
calculated to assess the weight/influence on the hypoechoic rim of each of the
variables showed as all variables, except the sex, significantly weighed on the
hypoechoic rim although the greatest weight was reached by a glomerular
filtration rate < 60 ml/min/1.73 m2 and a renal cortical thickness between 7 and
12 mm. The hypoechoic rim was found only when cortical thickness was between 7
and 12 mm while it was absent if the cortical thickness was less than 7 or
greater than 12 mm. We also found numerous cases of sidedness of the hypoechoic
rim. CONCLUSIONS: It is our opinion that in case of unilateral finding of an
hypoechoic rim, the association between the hypoechoic rim and the cortical
thinning is consistent and therefore more accurate than the correlation between
the presence of the hypoechoic rim and the reduction of the glomerular filtration
rate.
PMID- 28403600
TI - Blood platelet activity in men with vasculogenic erectile dysfunction.
AB - OBJECTIVE: The aim of this study was to investigate the platelet activity in
patients with vasculogenic erectile dysfunction (ED). MATERIALS AND METHODS: The
total blood count, including hemoglobin (Hgb), white blood cell (WBC), red blood
cell (RBC), platelet (PLT) and mean platelet volume (MPV) parameters were
measured in the patient (n = 70) and control groups (n = 50). RESULTS: The
average age was 48.1 +/- 11.7 and 47.6 +/- 12.3 in the patient and control groups
(p = 0.8217), respectively. MPV was higher in the patient group and there was a
statistically significant difference between two groups (11.27 +/- 0.56 and 9.8
+/- 0.91, p < 0.0001). PLT counts were lower in the patient group but there was
not a statistically significant difference (196.23 +/- 37.01 and 209.07 +/-
36.71, p = 0.0626). In terms of haemoglobin, WBC and RBC values, there was no
difference in the patient and control groups. CONCLUSIONS: Finding high MPV,
which reflects the platelet activity, in the patient group shows that platelets
also have a role in the VED etiopathogenesis. In the case of the confirmation of
this result with additional studies, the efficiency of anti-platelet therapy in
the vasculogenic ED should also be researched.
PMID- 28403601
TI - Urinary symptoms and sexual dysfunction among Italian men: The results of the
#Controllati survey.
AB - OBJECTIVE: Prevention may improve the quality of life and sexual and reproductive
health. To improve prevention require a comprehensive research approach that
examines the frequency and risk factors for urologic conditions. In June 2016 the
Italian Urologic Society coordinated a preventive initiative : the 1st Week of
Male Urologic Prevention "#Controllati". MATERIAL AND METHODS: During the 1st
Week of Male Urologic Prevention "#Controllati", men aged 18 years or more were
invited to attend participating urologic centers for a free of charge visit for
counseling about urologic or andrologic conditions. Each participating man
underwent a physical examination. Further he was asked about his a medical
history and about his urologic symptoms, sexual activity and possible related
problems. RESULTS: Data were collected in 81 centers: 2380 men answered the
questionnaire. A total of 1226 subjects participating in the study reported one
or more urinary symptom [51.5% (IC 95% 48.9%-54.5%)]. The risk of any urinary
symptoms increased with age: in comparison with men aged < = 30 years or less the
risk of any urinary symptoms was 2.31, 2.92, 5.12, 7.82 and 17.02 respectively in
the class age 31-40, 41-50, 51-60, 61-70 and > = 71. Overweight/obese men were at
increased risk of any urinary symptoms [OR1.35 (95% CI 1.12-1.64)]. 27.2% (IC 95%
overall 25.2% -29.3%) of the subjects had at least a sexual disorder (erectile
dysfunction, premature ejaculation, hypoactive sexual desire). The erectile
dysfunction and hypoactive sexual desire increased with age, but premature
ejaculation tended to be higher among younger aged men aged 40 years or more.
Current any urinary symptoms [OR 1.85 (CI 1.40-2.43)], hypertension [OR 1.66 (95%
CI 1.21-2.26) and diabetes (OR 2.37 (95% CI 1.45-3.88)] increased the risk of
erectile dysfunction. CONCLUSIONS: This large survey gives a picture of the
burden of the more frequent urologic conditions offering useful information in
order to focus preventive campaign.
PMID- 28403602
TI - Nonabsorbable polymer clip as a cause of chronic perineal pain after radical
prostatectomy: Description of a case treated by transperineal approach.
AB - The occurrence of persistent perineal pain caused by surgical clips has rarely
been described after radical prostatectomy (RP). We describe the case of a
patient complaining of chronic perineal pain occurred soon after robotic RP,
refractory to conventional medical therapy and exacerbated by the sitting
position. Pain was related to a nonabsorbable polymer clip used to secure lateral
pedicles. A transpeerineal approach was used to perform an hydrodissection of the
rectovesical space at the level of the surgical clip combined with local
injection of mepivacaine and betametasone. The patient experienced a clinically
significant reduction of pain that remained stable at three months' follow-up.
PMID- 28403603
TI - B-lymphocytic infiltration of the prostate to a patient with chronic lymphocytic
leukemia. A case report.
AB - Involvement of the prostate gland, as an early extra-nodal manifestation of a
hematologic disease, or as a secondary infiltration is rare. Even rarer is the
acute urinary retention due to infiltration by lymphocytes and simultaneously
enlarged prostate. We present a case of a 61 years old male patient with a
history of chronic lymphocytic leukemia, who was under oncological follow-up with
no active treatment and had typical lower urinary tract symptoms due to benign
prostatic hyperplasia and was receiving 5-alpha reductase inhibitor. After an
acute urinary retention episode which was managed with a suprapubic catheter due
to urethral catheter insertion failure, the patient was submitted to a
transurethral prostatectomy. Histological examination revealed lymphocytic
infiltration of the prostatic parenchyma by mostly small B cells. B-lymphocytic
infiltration of the prostate gland, causes symptoms similar to benign prostatic
hyperplasia. Acute urinary retention due to B-lymphocytic infiltration of the
prostate is rare and the diagnosis is always histological and an oncological re
evaluation is necessary. The prognosis of these patients is related to the
generalized disease rather than to the prostatic involvement.
PMID- 28403604
TI - Ultrasound findings of ruptured Peyronie's plaque: Case report and review of the
literature.
AB - We present here a rare case of rupture of tunica albuginea and corpus cavernosum,
in the site of a Peyronie's plaque, which happened in a 61- year-old man during a
vacuum cleaner masturbation. Ultrasound study showed an irregular hyperechoic
defect at the cavernosal rupture site in correspondence of the Peyronie's plaque.
The hematoma was evacuated, partially plaque excised, and the tear repaired.
Ultrasonography is an ideal technique for evaluating patients with penile trauma
and can be routinely used in an emergency. It is a non-invasive method that gives
faster results than cavernosography and Magnetic Resonance Imaging.
PMID- 28403605
TI - Sequential Gas-Phase Activation of Carbon Dioxide and Methane by [Re(CO)2]+: The
Sequence of Events Matters!
AB - The potential of carbonyl rhenium complexes in activating and coupling carbon
dioxide and methane has been explored by using a combination of gas-phase
experiments (FT-ICR mass spectrometry) and high-level quantum chemical
calculations. While the complexes [Re(CO)x]+ (x = 0, 1, 3) are thermally
unreactive toward CO2, [Re(CO)2]+ abstracts one oxygen atom from this substrate
spontaneously at ambient conditions. Based on 13C and 18O labeling experiments,
the newly generated CO ligand is preferentially eliminated, and two mechanistic
scenarios are considered to account for this unexpected finding. The oxo complex
[ORe(CO)2]+ reacts further with CH4 to produce the dihydridomethylene complex
[ORe(CO)(CH2)(H)2]+. However, coupling of the CO and CH2 ligands to form CH2?C?O
does not take place. Further, the complexes [Re(CO)x(CH2)]+ (x = 1, 2), generated
in the thermal reaction of [Re(CO)x]+ (x = 1, 2) with CH4, are inert toward CO2.
Mechanistic insight on the origin of this remarkable reactivity pattern has been
derived from detailed quantum chemical calculations.
PMID- 28403606
TI - Halogenated Organic Compounds Identified in Hydraulic Fracturing Wastewaters
Using Ultrahigh Resolution Mass Spectrometry.
AB - Large volumes of water return to the surface following hydraulic fracturing of
deep shale formations to retrieve oil and natural gas. Current understanding of
the specific organic constituents in these hydraulic fracturing wastewaters is
limited to hydrocarbons and a fraction of known chemical additives. In this
study, we analyzed hydraulic fracturing wastewater samples using ultrahigh
resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR
MS) as a nontargeted technique to assign unambiguous molecular formulas to singly
charged molecular ions. Halogenated molecular formulas were identified and
confirmed using isotopic simulation and MS-MS fragmentation spectra. The
abundance of halogenated organic compounds in flowback fluids rather than older
wastewaters suggested that the observed molecular ions might have been related to
hydraulic fracturing additives and related subsurface reactions, such as through
the reaction of shale-extracted chloride, bromide, and iodide with strong oxidant
additives (e.g., hypochlorite, persulfate, hydrogen peroxide) and subsequently
with diverse dissolved organic matter. Some molecular ions matched the exact
masses of known disinfection byproducts including diiodoacetic acid,
dibromobenzoic acid, and diiodobenzoic acid. The identified halogenated organic
compounds, particularly iodinated organic molecules, are absent from inland
natural systems and these compounds could therefore play an important role as
environmental tracers.
PMID- 28403607
TI - Copper-Catalyzed Dicarbofunctionalization of Unactivated Olefins by Tandem
Cyclization/Cross-Coupling.
AB - We present a strategy that difunctionalizes unactivated olefins in 1,2-positions
with two carbon-based entities. This method utilizes alkyl/arylzinc reagents
derived from olefin-tethered alkyl/aryl halides that undergo radical cyclization
to generate C(sp3)-Cu complexes in situ, which are intercepted with aryl and
heteroaryl iodides. A variety of (arylmethyl)carbo- and heterocycles (N, O) can
be synthesized with this new method.
PMID- 28403608
TI - Immobilization of a Cutinase from Fusarium oxysporum and Application in Pineapple
Flavor Synthesis.
AB - In the present study, the immobilization of a cutinase from Fusarium oxysporum
was carried out as cross-linked enzyme aggregates. Under optimal immobilization
conditions, acetonitrile was selected as precipitant, utilizing 9.4 mg protein/mL
and 10 mM glutaraldehyde as cross-linker. The immobilized cutinase (imFocut5a)
was tested in isooctane for the synthesis of short-chain butyrate esters,
displaying enhanced thermostability compared to the free enzyme. Pineapple flavor
(butyl butyrate) synthesis was optimized, leading to a conversion yield of >99%
after 6 h, with an initial reaction rate of 18.2 mmol/L/h. Optimal reaction
conditions were found to be 50 degrees C, a vinyl butyrate/butanol molar ratio
of 3:1, vinyl butyrate concentration of 100 mM, and enzyme loading of 11 U.
Reusability studies of imFocut5a showed that after four consecutive runs, the
reaction yield reaches 54% of the maximum. The efficient bioconversion offers a
sustainable and environmentally friendly process for the production of "natural"
aroma compounds essential for the food industry.
PMID- 28403609
TI - Solid State NMR Characterization of Ibuprofen:Nicotinamide Cocrystals and New
Idea for Controlling Release of Drugs Embedded into Mesoporous Silica Particles.
AB - Grinding and melting methods were employed for synthesis of pharmaceutical
cocrystals formed by racemic (R/S) and entiomeric (S) ibuprofen (IBU) and
nicotinamide (NA) as coformer. Obtained (R/S)-IBU:NA and (S)-IBU:NA cocrystals
were fully characterized by means of advanced one- and two-dimensional solid
state nuclear magnetic resonance (SS NMR) techniques with very fast magic angle
spinning (MAS) at 60 kHz. The distinction in molecular packing and specific
hydrogen bonding pattern was clearly recognized by analysis of 1H, 13C, and 15N
spectra. It is concluded from these studies that both methods (grinding and
melting) provide exactly the same, specific forms of cocrystals. Thermal solvent
free (TSF) approach was used for loading of (R/S)-IBU:NA and (S)-IBU:NA into the
pores of MCM-41 mesoporous silica particle (MSP). The progress and efficiency of
this process was analyzed by NMR spectroscopy. It has been confirmed that TSF
method is an effective and safe technique of filling the MSP pores with active
pharmaceutical ingredients (APIs). By analyzing the NMR results, it has been
further proved that excess of IBU and NA components, which are not embedded into
the pores during melting and cooling, crystallize on the MCM-41 walls preserving
very specific arrangement, characteristic for crystalline samples. By
investigating kinetic of release for (R/S)-IBU/MCM-41, (S)-IBU:NA/MCM-41, and
(R/S)-IBU:NA/MCM-41 samples containing active components exclusively inside of
the pores, it was revealed that release of IBU is much faster for the first of
the samples compared to those containing IBU and NA inside the pores. The
hypothesis that the rate of release of API can be controlled by specific
composition of cocrystal embedded into the MSP pore was further supported by
study of (R/S)-IBU:BA/MCM-41 sample with benzoic acid (BA) as coformer.
PMID- 28403610
TI - Confinement Effects on an Electron Transfer Reaction in Nanoporous Carbon
Electrodes.
AB - Nanoconfinement generally leads to a drastic effect on the physical and chemical
properties of ionic liquids. Here we investigate how the electrochemical
reactivity in such media may be impacted inside of nanoporous carbon electrodes.
To this end, we study a simple electron transfer reaction using molecular
dynamics simulations. The electrodes are held at constant electric potential by
allowing the atomic charges on the carbon atoms to fluctuate. We show that the
Fe3+/Fe2+ couple dissolved in an ionic liquid exhibits a deviation with respect
to Marcus theory. This behavior is rationalized by the stabilization of a
solvation state of the Fe3+ cation in the disordered nanoporous electrode that is
not observed in the bulk. The simulation results are fitted with a recently
proposed two solvation state model, which allows us to estimate the effect of
such a deviation on the kinetics of electron transfer inside of nanoporous
electrodes.
PMID- 28403611
TI - Potassium tert-Butoxide-Catalyzed Dehydrogenative C-H Silylation of
Heteroaromatics: A Combined Experimental and Computational Mechanistic Study.
AB - We recently reported a new method for the direct dehydrogenative C-H silylation
of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we
report a systematic experimental and computational mechanistic investigation of
this transformation. Our experimental results are consistent with a radical chain
mechanism. A trialkylsilyl radical may be initially generated by homolytic
cleavage of a weakened Si-H bond of a hypercoordinated silicon species as
detected by IR, or by traces of oxygen which can generate a reactive peroxide by
reaction with [KOt-Bu]4 as indicated by density functional theory (DFT)
calculations. Radical clock and kinetic isotope experiments support a mechanism
in which the C-Si bond is formed through silyl radical addition to the
heterocycle followed by subsequent beta-hydrogen scission. DFT calculations
reveal a reasonable energy profile for a radical mechanism and support the
experimentally observed regioselectivity. The silylation reaction is shown to be
reversible, with an equilibrium favoring products due to the generation of H2
gas. In situ NMR experiments with deuterated substrates show that H2 is formed by
a cross-dehydrogenative mechanism. The stereochemical course at the silicon
center was investigated utilizing a 2H-labeled silolane probe; complete
scrambling at the silicon center was observed, consistent with a number of
possible radical intermediates or hypercoordinate silicates.
PMID- 28403612
TI - Polymer-Coated Ultrastable and Biofunctionalizable Lanthanide Nanoparticles.
AB - Lanthanide-containing nanoparticles (LnNPs), for example, NaYF4, are considered
to be one of the most promising platforms for biological and material
applications due to their unique and unusual magnetic and upconversion
fluorescent properties. However, limited water dispersity, low long-term
colloidal stability, and difficulty in further functionalization greatly narrow
the scope of their application in the real world. Herein, we report a facile
strategy to counter the aforementioned barriers to the expanding use of LnNPs
that involves surface-coating the LnNPs with poly(ethylene glycol)-b
poly(pentafluorophenyl methacrylate)/phosphonic acid and subsequently shell cross
linking with NH2-PEG-NH2. The cross-linked PEG layer provided good water
dispersity, nonfouling characteristics, and excellent long-term colloidal
stability in phosphate-buffered saline in the range of 25-60 degrees C, whereas
the high reactivity of the pentafluorophenyl ester with the amino group brought
about ease of incorporation of functional moieties into LnNPs. Particularly, it
was found for the first time that LnNPs with surface coating could endure the
freeze-drying process without any sign of aggregation, which would not only
greatly decrease the weight and storage and shipping room but also increase the
storage shelf life with the preservation of their inherent properties, especially
for LnNPs with some fragile bioconjugates while in solution.
PMID- 28403613
TI - Thermal Transport at Solid-Liquid Interfaces: High Pressure Facilitates Heat Flow
through Nonlocal Liquid Structuring.
AB - The integration of three-dimensional microelectronics is hampered by overheating
issues inherent to state-of-the-art integrated circuits. Fundamental
understanding of heat transfer across soft-solid interfaces is important for
developing efficient heat dissipation capabilities. At the microscopic scale, the
formation of a dense liquid layer at the solid-liquid interface decreases the
interfacial heat resistance. We show through molecular dynamics simulations of n
perfluorohexane on a generic wettable surface that enhancement of the liquid
structure beyond a single adsorbed layer drastically enhances interfacial heat
conductance. Pressure is used to control the extent of the liquid layer
structure. The interfacial thermal conductance increases with pressure values up
to 16.2 MPa at room temperature. Furthermore, it is shown that liquid structuring
enhances the heat-transfer rate of high-energy lattice waves by broadening the
transmission peaks in the heat flux spectrum. Our results show that pressure is
an important external parameter that may be used to control interfacial heat
conductance at solid-soft interfaces.
PMID- 28403614
TI - Synthesis of Enantiomerically Pure (8S,9S,10R,6Z)-Trihydroxyoctadec-6-enoic Acid.
AB - We have accomplished the asymmetric synthesis of (8S,9S,10R,6Z)-trihydroxyoctadec
6-enoic acid in optically pure form and determined the absolute configuration of
the natural product on the basis of the stereodetermined chiral building block 7,
which was prepared by the catalytic enantioselective allylic oxidation of 4,5
epoxycyclohex-1-ene using an S-configured N,N-bidentate ligand-copper catalyst.
PMID- 28403615
TI - Students and Co-workers of Mark S. Gordon.
PMID- 28403617
TI - Publications of Mark S. Gordon.
PMID- 28403616
TI - Preface: Mark S. Gordon.
PMID- 28403618
TI - Poly(N-isopropyl acrylamide)-coated surfaces: Investigation of the mechanism of
cell detachment.
AB - Although there is a great deal of research focused on cell sheet engineering from
polymers such as poly(N-isopropyl acrylamide) (pNIPAM), the biocompatibility of
pNIPAM surfaces and the nature of cellular detachment from this polymer is still
unclear. The most extensive study of the mechanism of detachment proposed a two
step process, with a first (passive) phase involving hydration of pNIPAM chains,
and the second (active) phase involving cellular metabolism. However, a number of
studies performed successful cell sheet detachment from pNIPAM-grafted surfaces
at low temperatures which calls this hypothesis into question. Furthermore,
although it has been demonstrated that low-temperature cell sheet detachment
using pNIPAM-grafted surfaces is less destructive than other methods of
detachment, it has not been investigated if cell sheet detachment removes a
portion of pNIPAM from the surfaces as well. It is essential to know if any
fragments of the polymer are removed along with the cells, as small polymer
fragments could have cytotoxic effects on the cells. This is especially important
if these cells are used for the generation of tissues used for transplantation.
In this work, the mechanism of cell detachment from pNIPAM coated surfaces is
investigated by testing how temperature and presence of an adenosine
triphosephase inhibitor affect cellular detachment. Surface initiated atom
transfer polymerization (ATRP) was utilized to synthesize thermoresponsive
atrpNIPAM surfaces. pNIPAM surfaces were labeled to assess whether cell sheet
detachment from pNIPAM is accompanied by the removal of pNIPAM from the substrate
itself. Using a semipermeable superstrate, cell sheets were transferred to a
secondary culture dish to assess whether cell detachment resulted in any pNIPAM
removal. In addition, the function of the transplanted bovine aortic endothelial
cells was assessed by determining whether they would proliferate and grow on a
new secondary substrate.
PMID- 28403620
TI - Altered mental status predicts mortality in cardiogenic shock - results from the
CardShock study.
AB - BACKGROUND: Altered mental status is among the signs of hypoperfusion in
cardiogenic shock, the most severe form of acute heart failure. The aim of this
study was to investigate the prevalence of altered mental status, to identify
factors associating with it, and to assess the prognostic significance of altered
mental status in cardiogenic shock. METHODS: Mental status was assessed at
presentation of shock in 215 adult cardiogenic shock patients in a multinational,
prospective, observational study. Clinical picture, biochemical variables, and
short-term mortality were compared between patients presenting with altered and
normal mental status. RESULTS: Altered mental status was detected in 147 (68%)
patients, whereas 68 (32%) patients had normal mental status. Patients with
altered mental status were older (68 vs. 64 years, p=0.04) and more likely to
have an acute coronary syndrome than those with normal mental status (85% vs.
74%, p=0.04). Altered mental status was associated with lower systolic blood
pressure (76 vs. 80 mmHg, p=0.03) and lower arterial pH (7.27 vs. 7.35, p<0.001)
as well as higher levels of blood lactate (3.4 vs. 2.3 mmol/l, p<0.001) and blood
glucose (11.4 vs. 9.0 mmol/l, p=0.01). Low arterial pH (adjusted odds ratio 1.6
(1.1-2.2), p=0.02) was the only factor independently associated with altered
mental status. Ninety-day mortality was significantly higher (51% vs. 22%,
p<0.001) among patients with altered mental status. CONCLUSIONS: Altered mental
status is a common clinical sign of systemic hypoperfusion in cardiogenic shock
and is associated with poor outcome. It is also associated with several
biochemical findings that reflect inadequate tissue perfusion, of which low
arterial pH is independently associated with altered mental status.
PMID- 28403619
TI - Insulin-Like Growth Factor Is Associated with Changes in Body Composition with
Antiretroviral Therapy Initiation.
AB - Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have
been associated with body composition changes among HIV-infected persons with
wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with
antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS
Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource
Limited Settings (PEARLS) study was a prospective, randomized clinical trial of
ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus
lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals
from resource-diverse settings. IGF-1 was measured from baseline, week 48, and
week 96 stored serum samples. Multivariate models were constructed. 415
participants were included: 170 (41%) were randomized to FTC/TDF+EFV and 245
(59%) to 3TC/ZDV+EFV. The mean age was 35 years, 60% were black, 42% women. The
mean IGF-1 level did not change significantly from baseline to week 96 (-0.65
ng/ml; 95% confidence interval (CI) -5.18-3.87), p = .78 and there were no
differences by treatment arm at week 96, p = .74. Lower baseline IGF-1 was
associated with age, non-white race, greater waist-hip ratio (WHR), low CD4
count, and lower baseline albumin (all p < .01) but not plasma HIV-1 RNA, body
mass index, or treatment arm. Greater change in IGF-1 from baseline to 96 weeks
was associated with female sex, smaller WHR change, lower baseline albumin, and
higher baseline HIV-1 RNA (all p < .01). ART initiation with either ZDV or TDF
did not significantly impact overall IGF-1 levels. Baseline and on-treatment
changes in IGF-1 with ART initiation may be related to the body composition
changes that occur after ART initiation.
PMID- 28403621
TI - Examining Factors Affecting Caregiver Burden: A Comparison of Frontotemporal
Dementia and Alzheimer's Disease.
AB - This study was conducted to compare the caregiver burden with regard to
Alzheimer's disease (AD) and frontotemporal dementia (FTD) and to determine the
factors affecting the caregiver burden of patients with AD and FTD. A comparative
descriptive study design was used. The sample consisted of 90 patients with AD
and 44 patients with FTD and their caregivers. Sociodemographic questionnaire,
Mini-Mental State Examination (MMSE), the Caregiver Burden Inventory (CBI),
Neuropsychiatric Inventory (NPI), and Functional Activities Questionnaire (FAQ)
were used. Descriptive statistics, t tests, chi2 test, and multinominal
regression were used for analysis. No difference was found with subscales and the
total score of the CBI, except time dependency scale. The total NPI and FAQ
scores correlated significantly, and the MMSE score did not show a significant
correlation with the AD and FTD caregiver burden. The presence and frequency of
neuropsychological symptoms differ among patients with FTD and AD, and different
symptoms affect the caregiver burdens in both groups.
PMID- 28403623
TI - Lithium: A classic drug-Frequently discussed, but, sadly, seldom prescribed!
AB - OBJECTIVE: Distinguished authors in the field have repeatedly alerted
psychiatrists of the alarming trends in the treatment of bipolar disorders:
decline of lithium use, paralleled by the increase of prescribing anticonvulsants
and second-generation antipsychotic drugs. Research has been conducted in order
to explore the factors that led to this development and to provide arguments for
the need to reverse this trend. METHOD: This paper represents a narrative review
of the literature containing retrieved research articles focusing on the efficacy
of lithium. The papers included in this overview were published prior to June
2016; additional papers were identified by searching the reference lists of
reviewed articles. Taking into account the amount of literature available, no
search can be exhaustive; on the other hand, the studies consulted, all of which
explore the effectiveness of various compounds, may have their own limitations as
well. RESULTS: The evidence of the effectiveness of lithium in the treatment of
acute mania, acute bipolar depression and the prevention of manic and depressive
episodes is compelling. Lithium is the most effective augmentation agent in
treatment-resistant depression. Its anti-suicidal effects are well established.
The neuroprotective effects of lithium have been demonstrated in case-control
studies and in population-based research. It has been established that starting
lithium early in the course of the disorder reduces the rates of treatment non
response. CONCLUSIONS: Despite abundant evidence regarding the efficacy of
lithium and its effectiveness in the treatment of bipolar disorders, its use is
declining at the beginning of the 21st century. It is of paramount importance to
keep reminding psychiatrists and educating physicians about the unique properties
of lithium and about monitoring patients treated with lithium, since it has been
suggested that lithium should once again become the first-line treatment for
bipolar disorders.
PMID- 28403622
TI - Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in
Nondemented Community-Dwelling Older Adults.
AB - Little research exists examining the relationship between beta-amyloid neuritic
plaque density via [18F]flutemetamol binding and cognition; consequently, the
purpose of the current study was to compare cognitive performances among
individuals having either increased amyloid deposition (Flute+) or minimal
amyloid deposition (Flute-). Twenty-seven nondemented community-dwelling adults
over the age of 65 underwent [18F]flutemetamol amyloid-positron emission
tomography imaging, along with cognitive testing using the Repeatable Battery for
the Assessment of Neuropsychological Status (RBANS) and select behavioral
measures. Analysis of variance was used to identify the differences among the
cognitive and behavioral measures between Flute+/Flute- groups. Flute+
participants performed significantly worse than Flute- participants on RBANS
indexes of immediate memory, language, delayed memory, and total scale score, but
no significant group differences in the endorsed level of depression or
subjective report of cognitive difficulties were observed. Although these results
are preliminary, [18F]flutemetamol accurately tracks cognition in a nondemented
elderly sample, which may allow for better prediction of cognitive decline in
late life.
PMID- 28403624
TI - Intact endobronchial hydatid cyst: an unexpected bronchoscopic challenge.
AB - We describe a rare case of intact endobronchial hydatid cyst that posed a
diagnostic challenge because of an unusual imaging manifestation (atelectasis)
and unexpected bronchoscopic findings. Although the role of bronchoscopy in the
management of pulmonary hydatid cyst is still controversial, 6 cases of
complicated pulmonary hydatid cyst removed completely by suction through a
fiberoptic bronchoscope have been reported so far. To the best of our knowledge,
this is the first nonsurgically treated case of intact endobronchial hydatid cyst
with an uneventful long-term follow-up.
PMID- 28403625
TI - Development and validation of a prediction algorithm for the onset of common
mental disorders in a working population.
AB - OBJECTIVE: Common mental disorders are the most common reason for long-term
sickness absence in most developed countries. Prediction algorithms for the onset
of common mental disorders may help target indicated work-based prevention
interventions. We aimed to develop and validate a risk algorithm to predict the
onset of common mental disorders at 12 months in a working population. METHODS:
We conducted a secondary analysis of the Household, Income and Labour Dynamics in
Australia Survey, a longitudinal, nationally representative household panel in
Australia. Data from the 6189 working participants who did not meet the criteria
for a common mental disorders at baseline were non-randomly split into training
and validation databases, based on state of residence. Common mental disorders
were assessed with the mental component score of 36-Item Short Form Health Survey
questionnaire (score ?45). Risk algorithms were constructed following
recommendations made by the Transparent Reporting of a multivariable prediction
model for Prevention Or Diagnosis statement. RESULTS: Different risk factors were
identified among women and men for the final risk algorithms. In the training
data, the model for women had a C-index of 0.73 and effect size (Hedges' g) of
0.91. In men, the C-index was 0.76 and the effect size was 1.06. In the
validation data, the C-index was 0.66 for women and 0.73 for men, with positive
predictive values of 0.28 and 0.26, respectively Conclusion: It is possible to
develop an algorithm with good discrimination for the onset identifying overall
and modifiable risks of common mental disorders among working men. Such models
have the potential to change the way that prevention of common mental disorders
at the workplace is conducted, but different models may be required for women.
PMID- 28403626
TI - Direct factor IXa inhibition with the RNA-aptamer pegnivacogin reduces platelet
reactivity in vitro and residual platelet aggregation in patients with acute
coronary syndromes.
AB - BACKGROUND: Residual platelet reactivity is a predictor of poor prognosis in
patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary
intervention. Thrombin is a major platelet activator and upon initiation of the
coagulation cascade, it is subsequently produced downstream of factor IXa, which
itself is known to be increased in ACS. Pegnivacogin is a novel RNA-aptamer based
factor IXa inhibitor featuring a reversal agent, anivamersen. We hypothesized
that pegnivacogin could reduce platelet reactivity. METHODS: Whole blood samples
from healthy volunteers were incubated in vitro in the presence and absence of
pegnivacogin and platelet reactivity was analysed. In addition, platelet
aggregometry was performed in blood samples from ACS patients in the RADAR trial
featuring the intravenous administration of pegnivacogin as well as reversal by
anivamersen. RESULTS: In vitro, pegnivacogin significantly reduced adenosine
diphosphate-induced CD62P-expression (100% vs. 89.79+/-4.04%, p=0.027, n=9) and
PAC-1 binding (100% vs. 83.02+/-4.08%, p=0.010, n=11). Platelet aggregation was
reduced (97.71+/-5.30% vs. 66.53+/-9.92%, p=0.013, n=10) as evaluated by light
transmission aggregometry. In the presence of the RNA-aptamer reversal agent
anivamersen, neither CD62P-expression nor platelet aggregation was attenuated. In
patients with ACS treated with aspirin and clopidogrel, residual platelet
aggregation was significantly reduced 20 min after intravenous bolus of 1 mg/kg
pegnivacogin (100% versus 43.21+/-8.23%, p=0.020). CONCLUSION: Inhibition of
factor IXa by pegnivacogin decreases platelet activation and aggregation in
vitro. This effect was negated by anivamersen. In ACS patients, platelet
aggregation was significantly reduced after intravenous pegnivacogin. An aptamer
based anticoagulant inhibiting factor IXa therefore might be a promising
antithrombotic strategy in ACS patients.
PMID- 28403627
TI - Short Communication: Resolution of Tenofovir Disoproxil Fumarate Induced Fanconi
Syndrome with Switch to Tenofovir Alafenamide Fumarate in a HIV-1 and Hepatitis B
Coinfected Patient.
AB - Fanconi syndrome is a rare adverse effect of tenofovir disoproxil fumarate (TDF).
Tenofovir alafenamide fumarate (TAF) is a novel prodrug with less nephrotoxicity.
We report resolution of Fanconi syndrome in a HIV and hepatitis B coinfected
patient switched from TDF to TAF.
PMID- 28403628
TI - Integrated Care Pathways and Care Bundles for Dementia in Acute Care: Concept
Versus Evidence.
AB - Caring for people with dementia in acute settings is challenging and confounded
by multiple comorbidities and difficulties transitioning between community and
acute care. Recently, there has been an increase in the development and use of
integrated care pathways (ICPs) and care bundles for defined illnesses and
medical procedures, and these are now being promoted for use in dementia care in
acute settings. We present a review of the literature on ICPs and/or care bundles
for dementia care in the acute sector. This includes a literature overview
including "gray literature" such as relevant websites, reports, and government
publications. Taken together, there is clearly a growing interest in and clinical
use of ICPs and care bundles for dementia. However, there is currently
insufficient evidence to support the effectiveness of ICPs for dementia care in
acute settings and limited evidence for care bundles for dementia in this
setting.
PMID- 28403629
TI - Methylation of SLFN11 is a marker of poor prognosis and cisplatin resistance in
colorectal cancer.
AB - AIM: The expression of human SLFN11 was reported to sensitize cancer cells to DNA
damaging agents. This study is to explore the epigenetic change and the function
of SLFN11 in human colorectal cancer (CRC). MATERIALS & METHODS: Six CRC cell
lines and 128 primary CRC samples were used. RESULTS: SLFN11 was methylated in
55.47% (71/128) of primary CRC. The expression of SLFN11 was regulated by
promoter region methylation. Methylation of SLFN11 was significantly associated
with age, poor 5-year overall survival and 5-year relapse-free survival (all p <
0.05). SLFN11 suppressed CRC cell growth both in vitro and in vivo and sensitized
CRC cells to cisplatin. CONCLUSION: SLFN11 is frequently methylated in human CRC,
and the expression of SLFN11 is regulated by promoter region methylation.
Methylation of SLFN11 reduced the sensitivity of CRC cells to cisplatin.
PMID- 28403630
TI - Metastatic internal mammary lymph nodes or mimickers on parasternal
ultrasonography: focusing on their distribution and depth.
AB - Background Ultrasonography (US) is an important tool to evaluate the status of
internal mammary lymph node (IMN). US features of metastatic IMNs could help
determine when biopsy should be performed. Purpose To compare US features of
metastatic IMNs to those of benign entities. Material and Methods In women with
suspected IMN metastasis on US, their intercostal space (ICS) abnormalities were
classified into metastatic IMN, benign IMN, and lymph node (LN) mimickers. US
features, distribution, and depth of abnormalities in one ICS and involved ICS
level were analyzed. Results Among 66 ICS abnormalities in 53 women, 46 were
metastatic IMNs, ten were benign IMNs, and ten were LN mimickers. For metastatic
IMNs, the second ICS was the most commonly involved ICS (n = 22), followed by the
first (n = 13), the third (n = 8), and the fourth (n = 3). ICS level distribution
of metastatic IMNs was not significantly ( P = 0.5407) different from that of non
metastatic lesions. Metastatic IMNs were predominantly seen in the posterior
layer of ICS, significantly ( P < 0.0001) different from LN mimickers. Both
metastatic IMNs and non-metastatic lesions were evenly distributed over the
upper, middle, and lower part (in craniocaudal direction) of one ICS. Conclusion
Metastatic IMNs are more likely to be found in the posterior layer of ICS. This
can help distinguish them from LN mimickers. Any part (upper, middle, or lower)
of one ICS in craniocaudal direction could be involved. The second ICS was the
most commonly involved level.
PMID- 28403631
TI - Identification and evaluation of antibacterial agents present in lipophilic
fractions isolated from sub-products of Phoenix dactilyfera.
AB - In this study, the dried powder of seeds and pollen of Phoenix dactylifera was
extracted using Soxhlet extractor and biochemical composition of lipophilic
extracts was analysed by GCMS. Then, we have tested the antibacterial effect of
fatty acids and volatile compounds found in these sub-products. The results
revealed that the main fatty acids found in Deglet Nour seeds is are oleic acid
(42.06%) followed by capric acid (24.16%), Takerbucht seeds extract contains
mostly oleic acid (40.59%) and palmitic acid (20.19%), while Bent Kbala seed
extract is rich in cis-vaccenic acid (52.09%) followed by capric acid (16.71%).
Pollen extract have shown for the first time the richness in 14-methyl palmitic
acid (33.31%), linoleic acid (31.16%) and linolenic acid (25.78%). Some of these
elements seem to have a significant effect against some pathogenic bacteria.
PMID- 28403632
TI - Developmental Screening and Referrals: Assessing the Influence of Provider
Specialty, Training, and Interagency Communication.
AB - Previous studies have shown that different provider approaches, amount of
familiarity with the referral and screening process, and level of interagency
communication can increase or decrease the likelihood of caregivers completing a
recommended referral to early intervention (EI). We surveyed 60 family
practitioners and pediatricians at 2 primary care clinics to assess these
factors. Pediatricians were more likely than family practitioners to report
using, evaluating, and discussing the results of developmental screens. Providers
with more experience and recent training expressed more confidence in their
ability to describe the EI system to families. Most providers expressed a lack of
confidence in their own agency to complete referrals or EI to provide follow-up.
The knowledge gaps and communication problems identified in this study could
serve as a basis for future interventional work.
PMID- 28403633
TI - Radiographic Outcomes of Dorsal Distraction Distal Radius Plating for Fractures
With Dorsal Marginal Impaction.
AB - BACKGROUND: The purpose of this study is to compare radiographic outcomes of
patients treated with dorsal spanning plates with previously reported normal
values of radiographic distal radius anatomy and compare the results with prior
publications for both external fixation and internal fixation with volar locked
plates. METHODS: Patients with complex distal radius fractures including dorsal
marginal impaction pattern necessitating dorsal distraction plating at the
discretion of the senior authors (M.A.T. and M.A.I.) from May 30, 2013, to
December 29, 2015, were identified and included in the study. Retrospective chart
and radiograph review was performed on 19 patients, 11 male and 8 female, with
mean age of 47.83 years (22-82). No patients were excluded from the study.
RESULTS: All fractures united prior to plate removal. The average time the plate
was in place was 80.5 days (49-129). Follow-up radiographs showed average radial
inclination of 20.5 degrees (13.2 degrees -25.5 degrees ), radial height of 10.7
mm (7.5-14 mm), ulnar variance of -0.3 mm (-2.1 to 3.1 mm), and volar tilt of 7.9
degrees (-3 degrees to 15 degrees ). One patient had intra-articular step-off
greater than 2 mm. CONCLUSIONS: Dorsal distraction plating of complex distal
radius fractures yields good radiographic results with minimal complications. In
cases of complex distal radius fractures including dorsal marginal impaction
where volar plating is not considered adequate, a dorsal distraction plate should
be considered as an alternative to external fixation due to reduced risk for
infection and better control of volar tilt.
PMID- 28403634
TI - Potential use of secondary products of the agri-food industry for topical
formulations and comparative analysis of antioxidant activity of grape leaf
polyphenols.
AB - The aim of the present study was to develop a phytocosmetic using Vitis waste by
products, for use as a topical formulation for skin protection against
ultraviolet radiation damage. The study also evaluates the free radical scavenger
activity of the crude extracts of dried leaves of Vitis vinifera and Vitis
labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds.
Next, release and permeation studies of hydrogels were performed using Franz-type
diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes
antioxidant assays, whereas anthocyanins had higher antioxidant activity in
hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released
from hydrogels, and the flavonoid retention in porcine ear skin after eight hours
of permeation was below of limit of quantification for this compound. The
polyphenols present in Vitis are capable of absorbing UV and visible light,
justifying their potential as sunscreens for the development of a phytocosmetic.
PMID- 28403635
TI - One-domain approach for studying multiphase transport phenomena in biofilm
growing systems.
AB - The one-domain approach (ODA) was used as an alternative to solve fluid-biofilm
interfacial behavior in a 2-D model for diffusion-reaction-convection coupled
with prediction of irregular growth of biofilms via a cellular automaton
strategy. The simulations exhibited errors of <7% compared with the porosity of a
previously reported capillary experimental system. Additionally, biofilm surface
geometrical aspects were satisfactorily compared with reports of experimental and
similar rigorously simulated benchmark systems. The method developed was applied
to simulate typical biofilm systems predicting recirculation flow patterns,
interface concentration profiles, and clogging of the inlet section of the
capillary tube, which are phenomena that affect the efficiency of diverse
biotechnological applications, including membrane bioreactors and biofilters. The
ODA method applied to the governing equations of momentum and mass transfer
combined with a cellular automaton algorithm is a suitable and straightforward
approach for modeling solid-state fermentation at different sophistication
levels.
PMID- 28403636
TI - A content analysis of chronic fatigue syndrome and myalgic encephalomyelitis in
the news from 1987 to 2013.
AB - Objectives The aim of this study was to analyze the content of American newspaper
articles ( n=214) from 1987 to 2013, in order to understand how the public
digests information related to Chronic Fatigue syndrome, a controversial and
misunderstood illness. Methods A novel codebook derived from the scientific
literature was applied to 214 newspaper articles collected from Lexis Nexis
Academic(r). These articles were coded quantitatively and frequency tables were
created to delineate the variables as they appeared in the articles. Results The
etiology was portrayed as organic in 64.5% ( n=138) of the articles, and there
was no mention of case definitions or diagnostic criteria in 56.1% ( n=120) of
the articles. The most common comorbidity was depression, appearing in 22.9% (
n=49) of the articles. In 55.6% ( n=119) of the articles, there was no mention of
prevalence rates. In 50.9% ( n=109) of the articles, there was no mention of any
form of treatment for the illness. A total of 19.4% ( n=42) of the headlines
mislabeled the name of the illness. Discussion Based on descriptive statistics of
all 214 coded articles, media communicated mixed messages for salient variables
such as the name of the illness, its etiology and treatment.
PMID- 28403637
TI - Monitor Polyimide Production from Diamine and Dianhydride Reactions Using a
Combination of In Situ Infrared and Raman Spectroscopy.
AB - A two-step synthesis of polyimide reaction from dianhydride and diamine was
followed by both infrared (IR) and Raman spectroscopy in situ in this case study.
In the first step, the two reactants form poly(amide acid), which resulted in
substantial spectral changes easily detected by both spectroscopic techniques.
The reaction was found to occur rapidly and reached completion within tens of
minutes at room temperature. In the second step, trimethylamine (catalyst) and
acetic anhydride (dehydration agent) were added to form the five-member imide
ring. Interestingly, different spectral changes were observed using IR and Raman
spectroscopic methods due to their different responses toward the various
functional groups involved. Conclusive evidence was also obtained based on the
Raman results to demonstrate a long-lived intermediate species, which was harder
to observe in the IR results. This work provides a good case study of the
combined use of different vibrational spectroscopy techniques to extract maximum
information from a reaction system.
PMID- 28403639
TI - A new cycloartane triterpenoid glycoside from Souliea vaginata.
AB - One new cycloartane triterpenoid glycoside, soulieoside Q (1), together with four
known compounds (2-5) were isolated from the ethanolic extract of the rhizomes of
Souliea vaginata Maxim. The structure of the new compound was determined by
extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, as well as
chemical methods. Compound 1 was evaluated for its cytotoxic activities against
HepG2 and A549 cancer cell lines.
PMID- 28403640
TI - A kaempferol triglycoside from Tephrosia preussii Taub. (Fabaceae).
AB - A phytochemical investigation of the MeOH extract of twigs and leaves of
Tephrosia preussi was carried out to give a new kaempferol triglycoside, named
tephrokaempferoside (1), together with five known compounds: tephrosin (2),
betulinic acid (3), lupeol (4), beta-sitosterol (5) and 3-O-beta-d
glucopyranoside of beta-sitosterol (6). The structure of the new compound was
characterised by analyses of NMR (1D and 2D) and MS data, and chemical
conversion. Tephrokaempferoside (1) had weak antibacterial activity against
Klebsiella pneumoniae with an MIC value of 150 MUg/mL.
PMID- 28403641
TI - Two new cytochalasan derivatives from Chaetomium globosum SNSHI-5, a fungus
derived from extreme environment.
AB - Two new cytochalasan derivatives, isochaetoglobosin Db (1) and cytoglobosin Ab
(2), were isolated from an ethyl acetate extract of Chaetomium globosum SNSHI-5,
a fungus derived from extreme environment. The structures of the new compounds
were comprehensively characterized by HR-ESI-MS, 1H NMR, 13C NMR and 2D-NMR.
Cytotoxic activity against H292 human lung cancer cell of the new compounds was
tested. Isochaetoglobosin Db (1) showed potent cytotoxicity with IC50 of 3.5 MUM,
while cytoglobosin Ab was inactive (IC50 > 10 MUM).
PMID- 28403645
TI - Classification: The key to understanding facial pain.
AB - It is indisputable that the global scientific advances in headache research, be
it bench or bedside, have benefited enormously from the operational diagnostic
criteria published in 1988. Today, this classification system is indispensable.
The reason for this success is a low inter-rater variability. In general,
orofacial pain conditions are less well characterised - with the noticeable
exemption of temporomandibular disorder pain. Tremendous work has been put into
changing this, and significant progress has been achieved - in particular, in
terms of the clinical implications and overriding conceptual models for oro
facial pain. Scientific classifications have only one goal: To provide a
scientific agreement about the main features of an object of research and a
scientific consensus regarding the name. The main significance is not the fact
that a good classification offers a detailed and accurate image of the reality.
If we want to overcome the obstacles of different competing classification
systems, we need to overcome specialisation borders. The key to success is to
understand that such a definition does not mirror all possible clinical facets of
a given pain condition but is simply a convention - that is, a consensus on a
word used for a pain condition. Simply speaking, a classification creates a
common language to be used by more than one profession. It will be crucial to
define any given pain condition as precisely and rigid as possible, in order to
ensure a homogenous population. Only this ensures a low inter-rater variability,
which consequently allows combining and comparing research on a population across
different professional settings. This is not easy for chronic facial pain without
verifiable morphological cause or structural lesions, as these syndromes are
often rather featureless. The new IASP classification of chronic pain is a big
step forward to a better characterisation of such conditions, and will trigger
future work on a new and operationalised classification of oro-facial pain.
PMID- 28403644
TI - The effect of basal insulin glargine on the fibrinolytic system and von
Willebrand factor in people with dysglycaemia and high risk for cardiovascular
events: Swedish substudy of the Outcome Reduction with an Initial Glargine
Intervention trial.
AB - INTRODUCTION: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue
plasminogen activator, tissue plasminogen activator/plasminogen activator-complex
and the haemostatic factor von Willebrand factor are known markers of
cardiovascular disease. Their plasma levels are adversely affected in patients
with dysglycaemia, and glucose normalization with insulin glargine might improve
the levels of these factors. METHODS: Prespecified Swedish substudy of the
Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov
number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen
activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen
activator/plasminogen activator inhibitor-1 complex and von Willebrand factor
were analysed at study start, after 2 years and at the end of the study (median
follow-up of 6.2 years). RESULTS: Of 129 patients (mean age of 64 +/- 7 years,
females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and
standard care group, respectively. Allocation to insulin glargine did not
significantly affect the studied fibrinolytic markers or von Willebrand factor
compared to standard care. Likewise, there were no significant differences in
plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von
Willebrand factor. During the whole study period, the within-group analysis
revealed a curvilinear pattern and significant changes for tissue plasminogen
activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator
antigen and von Willebrand factor in the insulin glargine but not in the standard
care group. CONCLUSION: In people with dysglycaemia and other cardiovascular risk
factors, basal insulin does not improve the levels of markers of fibrinolysis or
von Willebrand factor compared to standard glucose-lowering treatments.
PMID- 28403646
TI - Neuropathic orofacial pain: Facts and fiction.
AB - Definition and taxonomy This review deals with neuropathic pain of traumatic
origin affecting the trigeminal nerve, i.e. painful post-traumatic trigeminal
neuropathy (PTTN). Symptomatology The clinical characteristics of PTTN vary
considerably, partly due to the type and extent of injury. Symptoms involve
combinations of spontaneous and evoked pain and of positive and negative
somatosensory signs. These patients are at risk of going through unnecessary
dental/surgical procedures in the attempt to eradicate the cause of the pain, due
to the fact that most dentists only rarely encounter PTTN. Epidemiology Overall,
approximately 3% of patients with trigeminal nerve injuries develop PTTN.
Patients are most often female above the age of 45 years, and both physical and
psychological comorbidities are common. Pathophysiology PTTN shares many
pathophysiological mechanisms with other peripheral neuropathic pain conditions.
Diagnostic considerations PTTN may be confused with one of the regional
neuralgias or other orofacial pain conditions. For intraoral PTTN, early stages
are often misdiagnosed as odontogenic pain. Pain management Management of PTTN
generally follows recommendations for peripheral neuropathic pain. Expert opinion
International consensus on classification and taxonomy is urgently needed in
order to advance the field related to this condition.
PMID- 28403647
TI - Parathyroid Hormone-Related Peptide: A Novel Endocrine Cardioprotective
"Conditioning Mimetic".
AB - An as-yet limited body of evidence suggests that calcium-regulating endocrine
hormones-in particular, parathyroid hormone-related peptide (PTHrP)-may have
unappreciated cardioprotective effects. The current review focuses on the concept
that PTHrP may, via modulation of classic cardioprotective signaling pathways,
provide a novel strategy to attenuate myocardial ischemia-reperfusion injury.
PMID- 28403648
TI - Consumption of apple-boysenberry beverage decreases salivary Actinomyces
naeslundii and their adhesion in a multi-species biofilm model.
AB - We hypothesised that consumption of beverage rich in both fibre and polyphenols,
rather than each bioactive alone, will modulate populations of selected salivary
bacteria, and their adhesion characteristics and that some of these effects may
be due to the anti-microbial activity of the beverage bioactives. We investigated
the effect of 4 weeks' consumption of beverages, rich in apple fibre, boysenberry
polyphenols, or both on salivary bacteria in healthy subjects. In this placebo
controlled crossover study, saliva samples were collected at the beginning and
end of each treatment period, and used for qPCR quantitation of Lactobacillus
spp., Actinomyces naeslundii and Streptococcus mutans. The counts of salivary A.
naeslundii decreased after the consumption of the apple-boysenberry beverage
(P<0.05, Student's t-test). We also examined the effect of the subjects' saliva
on bacterial adhesion using a mixed species biofilm model. The salivary pellicles
prepared before and after each treatment were inoculated with laboratory strains
of A. naeslundii, Lactobacillus rhamnosus and S. mutans and tested for biofilm
formation. The post appleboysenberry beverage salivary pellicle significantly
decreased the adhesion of A. naeslundii at the end of both 3 and 24 h, in the in
vitro biofilm. A 1/16 dilution of the apple-boysenberry beverage itself decreased
the proliferation of test strains of A. naeslundii and S. mutans by 51 and 55%,
respectively (P<0.005), indicating the antimicrobial activity of its bioactives.
This study demonstrated that consumption of apple-boysenberry beverage, rather
than apple or the boysenberry beverage alone or the placebo, decreased salivary
A. naeslundii and their adhesion under laboratory conditions. These changes are
factors that influence oral microecology and potentially oral health.
PMID- 28403649
TI - A survey of probiotic use practices among patients at a tertiary medical centre.
AB - Probiotic use has skyrocketed in recent years. Little is known, however, about
patient knowledge and practices regarding probiotic use, especially in the
context of antibiotic use. An invitation to complete a short, anonymous,
electronic survey was sent by email to 965 patients at a tertiary medical centre
in California who had agreed to be contacted for participation in research
studies. Questions were asked about both probiotic and antibiotic use in the
prior three months. Of 333 survey respondents, 55% had recently used probiotics,
including food products and/or supplements (90 and 60% of probiotic users,
respectively). Women were more likely than men to have used probiotics (odds
ratio (OR): 1.99; 95% confidence interval (CI): 1.2-3.4). Health care providers
(HCP) had prescribed antibiotics to 79 (24%) respondents in the preceding three
months. Among antibiotic users, 33% had initiated or changed probiotics at the
time of antibiotic use, usually without a recommendation from their prescribing
HCP (72%). Only 12% of those who took probiotics with antibiotics had received a
specific recommendation from their HCP. Most patients chose to take probiotic
mixtures (56%), with few selecting evidence-based strains, such as Lactobacillus
rhamnosus GG (11%). Regular probiotic use among patients is common. Typically,
these probiotics are not recommended by a HCP, even in conjunction with
antibiotic prescriptions. While a growing body of evidence supports specific
probiotic strains for the prevention of antibiotic-associated diarrhoea, patients
are often not receiving a specific recommendation from their HCP and appear to be
taking strains without guidance from supporting evidence.
PMID- 28403650
TI - A new contribution to the history of probiotics.
PMID- 28403651
TI - Phytochemical components, total phenol and mineral contents and antioxidant
activity of six major medicinal plants from Rayen, Iran.
AB - The aim of this work was to evaluate the phytochemical components, minerals, the
antioxidant activity and total phenol contents of the essential oil from aerial
parts of six major medicinal plants in Rayen, Iran. The plants included
Ranunculus arvensis, Teucrium polium, Dracocephalum polychaetum, Kelussia
odoratissima, Artemisia sieberi and Thymus kotschyanus. Total phenol content
ranged from 0.03 to 0.158 mg/mL. A. sieberi showed the highest radical scavenging
ability (IC50 = 94 MUg/mL). The amount of minerals ranged as follows: P (0.23
29%), K (1.08-4.76%), Ca (0.78-2.35%), Mg (0.24-0.94%), Cu (8.3-15 mg/kg), Cd
(0.7-1.1 mg/kg), Pb (2-11.7 mg/kg) and Fe (250-1280 mg/kg). A total of 79
compounds were identified across all plants. The main components studied in the
plants were l-perillaldehyde, biosol, carvacrol, 1,8-cineol, terpinyl acetate and
1,2,3,6,7,7 a-hexahydro-5 h-inden 5-one.
PMID- 28403652
TI - A contribution to pharmaceutical biology of freshwater sponges.
AB - In vitro anti-tumour and anti-radical activities of the acetone extract of the
freshwater sponge Ochridaspongia rotunda were the subject of this study. The
extract was found to be highly cytotoxic to human lung tumour cell line A-549
reaching IC50 value of 5.01 +/- 0.21 MUg/mL. Indeed, it displayed only 2-fold
less anti-tumour activity than doxorubicin (IC50 value 2.42 +/- 0.13 MUg/mL) used
as a positive control. The same extract was also found to be almost 37-fold more
selective against A-549 vs. MRC-5 (normal) lung cells, in difference to weak
selectivity of doxorubicin (less than 3-fold). Its profound anti-DPPH radical
activity comparable to that of quercetin (IC50 values 3.68 +/- 0.19 and 3.14 +/-
0.09 MUg/mL, respectively) coupled with no signs of genotoxicity in the comet
assay (MRC-5 cell line, vs. doxorubicin) has actually implicated the importance
of this animal bioresource in searching for pharmaceutically useful bioactive
compounds of natural origin.
PMID- 28403653
TI - Congenital Pseudoarthrosis of the Distal Radius Treated With Physeal-Sparing
Double-Barrel Vascularized Free Fibula Transfer: A Case Report.
AB - BACKGROUND: Neurofibromatosis type 1 is a hereditary disease that can lead to
pseudoarthrosis of various long bones. Rarely, pseudoarthrosis affects the
forearm, and to the best of our knowledge, this is the first reported case of
pseudarthrosis of the distal radius treated by this unique method. METHODS: We
present a case of a 7-year-old male who underwent multiple operations to treat
pseudoarthrosis of the distal radius. RESULTS: After failed conservative and
operative fixation augmented with autologous iliac crest bone grafting, the
patient underwent a successful double-barrel vascularized free fibula graft while
preserving the physis of the distal radius. CONCLUSION: Double-barrel
vascularized free fibula bone graft can be successfully used as the definitive
treatment in refractory cases of distal forearm pseudarthrosis and we believe
that our technique can be applied to all cases of pseudarthrosis in other
patients with a similar presentation and lesion location.
PMID- 28403654
TI - Babyboy/Babygirl: A National Survey on the Use of Temporary, Nondistinct Naming
Conventions for Newborns in Neonatal Intensive Care Units.
PMID- 28403655
TI - Prevalence, Mortality, and Health Care Use among Patients with Cluster B
Personality Disorders Clinically Diagnosed in Quebec: A Provincial Cohort Study,
2001-2012.
AB - BACKGROUND: Cluster B personality disorders (PDs) are prevalent mental health
conditions in the general population (1%-6% depending on the subtype and study).
Affected patients are known to be heavier users of both mental and medical health
care systems than patients with other clinical conditions such as depression.
METHODS: Several rates were estimated using data from the integrated monitoring
system for chronic diseases in the province of Quebec, Canada. It provides a
profile of annual and period prevalence rates, mortality rates, and years of lost
life as well as health care utilisation rates for Quebec residents. All Quebec
residents are covered by a universal publicly managed care health plan. It is
estimated that the monitoring system includes 99% of Quebec's 8 million
inhabitants. RESULTS: Quebec residents aged 14 years and older were included in
the study. The lifetime prevalence of cluster B PDs was 2.6%. The mean years of
lost life expectancy were 13 for men and 9 for women compared to the provincial
population. The 3 most important causes of death are suicide (20.4%),
cardiovascular diseases (19.1%), and cancers (18.6%). In 2011 to 2012, 78% had
consulted a general practitioner and 62% a psychiatrist, 44% were admitted to an
emergency department, and 22% were hospitalised. CONCLUSIONS: Considering
mortality, cluster B personality disorder is a severe condition, is highly
prevalent in the population, and is associated with heavy health care services
utilisation, especially in emergency settings.
PMID- 28403656
TI - Online Training in Mind-Body Therapies: Different Doses, Long-term Outcomes.
AB - BACKGROUND: There is a high rate of burnout among health professionals, driving
diverse attempts to promote resilience and well-being to counter this trend. The
purpose of this project was to assess the dose-response relationship between the
number of hours of online mind-body skills training for health professionals and
relevant outcomes a year later. METHODS: Among 1438 registrants for online
training (including up to 12 hours of training on mind-body practices) between
December 2013 and November 2015, we analyzed responses from the first 10% who
responded to an anonymous online survey between December 1, 2015 and February 1,
2016. Questions included the type and frequency of mind-body practice in the past
30 days and whether the online training had any impact on personal life or
professional practice. Standardized measures were used to assess stress,
mindfulness, confidence in providing compassionate care, and burnout. RESULTS:
The 149 respondents represented a variety of ages and health professions; 55%
completed one or more mind-body training modules an average of 14 months
previously. Most (78%) engaged in one or more mind-body practices in the 30 days
before the survey; 79% reported changes in self-care and 71% reported changes in
the care of others as a result of participating. Increasing number of hours of
training were significantly associated with practicing mind-body skills more
frequently; increasing practice frequency was associated with less stress and
burnout, which were associated with missing less work. Greater practice frequency
was also associated with improvements in stress, mindfulness, and resilience,
which were associated with increased confidence in providing compassionate care.
CONCLUSION: Online training in mind-body therapies is associated with changes in
self-reported behavior one year later; increasing doses of training are
associated with more frequent practice which is associated with less stress,
burnout, and missing work, and higher levels of mindfulness, resilience, and
confidence in providing compassionate care. Additional studies are needed to
compare mind-body skills training with other interventions designed to improve
resilience and compassion while decreasing burnout in health professionals.
PMID- 28403658
TI - In vitro growth inhibition and cytotoxicity of Euphorbia caducifolia against four
human cancer cell lines and its phytochemical characterisation.
AB - Several Euphorbia species have been used in folklore as cancer remedies, however,
scientific studies on the cytotoxicity (in vitro studies) of Euphorbia
caducifolia are lacking. In present study, anticancer potential of E. caducifolia
aerial parts ethanol extract and its fractions were evaluated against human lung
(NCI-H460), breast (MCF-7), prostate (PC-3) and cervical (HeLa) cancer cell
lines, using sulphorhodamine-B in vitro cytotoxicity (in vitro studies) assay.
The ethanol extract demonstrated growth inhibitory effect against all
aforementioned cancer cell lines with IC50, 19-135 MUg/mL and LC50, ~220 MUg/mL,
and its petroleum ether fraction obtained on bioactivity guided fraction showed
highest activity with IC50, 28-70 MUg/mL and LC50, 71 MUg/mL against NCI-H460 and
MCF-7 cell lines. Its phytochemicals were analysed by gas chromatography-mass
spectrometry (GC-MS). The present study provides scientific justification for its
traditional use against cancer.
PMID- 28403659
TI - Immunizing Children: A Qualitative Analysis of Future Parental Decision Making.
AB - Vaccinations are considered one of public health's greatest accomplishments.
Despite evidence for vaccine effectiveness, uptake levels are still well below
the Centers for Disease Control and Prevention's guidelines. The immunization
decision-making process for parents is complex and depends on factors associated
with knowledge and experiences. This qualitative study sought to expand on a
previous decision-making model for immunizations by examining how individuals
receive vaccination information, determining the role of experience in
influencing decisions, and understanding how young adults might locate
vaccination information in the future. Three focus groups were conducted with 29
undergraduate students without children. Results suggest that young adults
exhibit an awareness of information regarding vaccine use and effectiveness,
value doctor opinions and recommendations, and desire more robust research on
vaccinations. Implications of these results include the importance of (1)
disseminating vaccination education to young adults, (2) enhancing
consistency/trust between medical professionals and youth, and (3) expanding
public policy to increase vaccine uptake.
PMID- 28403661
TI - Pediatric Cheerleading Injuries Treated in Emergency Departments in the United
States.
AB - This study investigates the epidemiology of cheerleading injuries to children in
the United States. Data were analyzed from the National Electronic Injury
Surveillance System for children 5 through 18 years of age treated in US
emergency departments for cheerleading injuries from 1990 through 2012. An
estimated 497 095 children ages 5 to 18 years were treated in US emergency
departments for a cheerleading injury during the 23-year study period, averaging
21 613 injured children per year. From 1990 to 2012, the annual cheerleading
injury rate increased significantly by 189.1%; and from 2001 to 2012, the annual
rate of cheerleading-related concussion/closed head injury increased
significantly by 290.9%. Falls were the most common mechanism of injury (29.4%)
and were more likely to lead to hospitalization (relative risk = 2.47; 95%
confidence interval = 1.67-3.68) compared with other injury mechanisms. The
rising number and rate of pediatric cheerleading injuries underscore the need for
increased efforts to prevent these injuries.
PMID- 28403660
TI - Value-based choice: An integrative, neuroscience-informed model of health goals.
AB - OBJECTIVE: Traditional models of health behaviour focus on the roles of
cognitive, personality and social-cognitive constructs (e.g. executive function,
grit, self-efficacy), and give less attention to the process by which these
constructs interact in the moment that a health-relevant choice is made. Health
psychology needs a process-focused account of how various factors are integrated
to produce the decisions that determine health behaviour. DESIGN: I present an
integrative value-based choice model of health behaviour, which characterises the
mechanism by which a variety of factors come together to determine behaviour.
This model imports knowledge from research on behavioural economics and
neuroscience about how choices are made to the study of health behaviour, and
uses that knowledge to generate novel predictions about how to change health
behaviour. I describe anomalies in value-based choice that can be exploited for
health promotion, and review neuroimaging evidence about the involvement of
midline dopamine structures in tracking and integrating value-related information
during choice. I highlight how this knowledge can bring insights to health
psychology using illustrative case of healthy eating. CONCLUSION: Value-based
choice is a viable model for health behaviour and opens new avenues for mechanism
focused intervention.
PMID- 28403662
TI - Diagnostic Efficacy of Serum Amyloid A Protein and Soluble Intercellular Adhesion
Molecule 1 in Pediatric Ventilator-Associated Pneumonia.
AB - OBJECTIVES: Study of inflammatory biomarkers which may aid in early detection of
ventilator-associated pneumonia (VAP) in children and predicting their outcome.
PATIENTS: Thirty-five children, aged 2 months to 13 years, needed mechanical
ventilation (MV) for more than 48 hours due to causes other than pneumonia.
METHODS: Measurement of serum amyloid A (SAA) protein, soluble intercellular
adhesion molecule 1 (sICAM-1), and C-reactive protein (CRP), modified clinical
pulmonary infection score (CPIS) and performing culture of endotracheal aspirate
at the start and on the third day of MV. RESULTS: Ventilator-associated pneumonia
was diagnosed by CPIS in 6 (17.1%) of 35 patients. On the third day of MV, there
was a significant increase in serum mean levels of SAA, sICAM-1, and CRP in
comparison to the start of MV ( P = .005, .004, and .01, respectively). Three
(50%) of 6 patients with VAP died, while 4 (14.28%) of 28 patients without VAP
died. The sensitivity of serum SAA, sICAM-1, and CPIS were 100% for predicting
VAP, while specificity was highest for CPIS (96.55%) followed by SAA (93.1%).
Combination of CPIS and SAA increased the specificity to 100%. For predicting
nonsurvival, serum SAA and sICAM-1 had a sensitivity of 100% and a specificity of
92.86% and 89.29%, respectively. CONCLUSION: Serum amyloid A and sICAM-1 may be
considered as reliable markers for detection of VAP. Combination of serum SAA
with CPIS increased the specificity to 100%. Measurement of SAA in patients with
VAP also had a good predictive value for nonsurvival in such patients.
PMID- 28403663
TI - Rapidly Expanding Giant Left Atrial Pseudoaneurysm in the Fetus.
PMID- 28403664
TI - Milk Options Observation (MOO): A Mixed-Methods Study of Chocolate Milk Removal
on Beverage Consumption and Student/Staff Behaviors in a Rural Elementary School.
AB - Providing flavored milk in school lunches is controversial, with conflicting
evidence on its impact on nutritional intake versus added sugar consumption and
excess weight gain. Nonindustry-sponsored studies using individual-level analyses
are needed. Therefore, we conducted this mixed-methods study of flavored milk
removal at a rural primary school between May and June 2012. We measured beverage
selection/consumption pre- and post-chocolate milk removal and collected
observation field notes. We used linear and logistic mixed models to assess
beverage waste and identified themes in staff and student reactions. Our analysis
of data from 315 unique students and 1,820 beverages choices indicated that
average added sugar intake decreased by 2.8 g postremoval, while average
reductions in calcium and protein consumption were negligible (12.2 mg and 0.3 g,
respectively). Five thematic findings emerged, including concerns expressed by
adult staff about student rebellion following removal, which did not come to
fruition. Removing flavored milk from school-provided lunches may lower students'
daily added sugar consumption without considerably decreasing calcium and protein
intake and may promote healthy weight.
PMID- 28403665
TI - Oregon School-Based Health Centers and Sexual and Contraceptive Behaviors Among
Adolescents.
AB - This study investigated the association between school-based health centers
(SBHCs) and sexual behavior and contraceptive use among 11th graders. The sample
included 134 high schools (27 schools with SBHCs) and 11,840 students who
participated in the 2015 Oregon Healthy Teens Survey. Multilevel logistic
regressions found positive associations between SBHC presence and healthy sexual
behavior ( OR = 1.23, p < .05) and contraceptive use ( OR = 1.31, p < .01).
Associations were stronger at schools with at least 50% of students receiving
free or reduced price lunch. Among SBHC schools, prescribing and dispensing
contraceptives onsite was positively related to contraceptive use among students
who had sex within the past 3 months ( OR = 1.77, p < .01). Findings suggest that
exposure to SBHCs in general, and availability of specific reproductive health
services, may be effective population-based strategies to support healthy sexual
behaviors among youth.
PMID- 28403666
TI - Enhanced acyclovir delivery using w/o type microemulsion: preclinical assessment
of antiviral activity using murine model of zosteriform cutaneous HSV-1
infection.
AB - The present study was aimed to develop and evaluate a microemulsion-based dermal
drug delivery of an antiviral agent, acyclovir. A water-in-oil microemulsion was
prepared using isopropyl myristate, Tween 20, Span 20, water and
dimethylsulphoxide. It was characterized for drug content, stability, globule
size, pH, viscosity and ex vivo permeation through mice skin. In vivo antiviral
efficacy of optimized formulation was assessed in female Balb/c mice against
herpes simplex virus-I (HSV-I)-induced infection. It was observed that optimized
formulation when applied 24-h post-infection could completely inhibit the
development of cutaneous herpetic lesions vis-a-vis marketed cream.
PMID- 28403667
TI - A computational model for predicting transmembrane regions of retroviruses.
AB - Transmembrane region (TR) is a conserved region of transmembrane (TM) subunit in
envelope (env) glycoprotein of retrovirus. Evidences have shown that TR is
responsible for anchoring the env glycoprotein on the lipid bilayer and
substitution of the TR for a covalently linked lipid anchor abrogates fusion.
However, universal software could not achieve sufficient accuracy as TM in env
also has several motifs such as signal peptide, fusion peptide and
immunosuppressive domain composed largely of hydrophobic residues. In this paper,
a support vector machine-based (SVM) model is proposed to identify TRs in
retroviruses. Firstly, physicochemical and evolutionary information properties
were extracted as original features. And then, the feature importance was
analyzed by minimum Redundancy Maximum Relevance (mRMR) feature selection
criterion. Our model achieved an Sn of 0.955, Sp of 0.998, ACC of 0.995, MCC of
0.954 using 10-fold cross-validation on the training dataset. These results
suggest that the proposed model can be used to predict TRs in non-annotation
retroviruses and 11917, 3344, 2, 289 and 6 new putative TRs were found in HERV,
HIV, HTLV, SIV, MLV, respectively.
PMID- 28403668
TI - NEAT-FLEX: Predicting the conformational flexibility of amino acids using
neuroevolution of augmenting topologies.
AB - The development of computational methods to accurately model three-dimensional
protein structures from sequences of amino acid residues is becoming increasingly
important to the structural biology field. This paper addresses the challenge of
predicting the tertiary structure of a given amino acid sequence, which has been
reported to belong to the NP-Complete class of problems. We present a new method,
namely NEAT-FLEX, based on NeuroEvolution of Augmenting Topologies (NEAT) to
extract structural features from (ABS) proteins that are determined
experimentally. The proposed method manipulates structural information from the
Protein Data Bank (PDB) and predicts the conformational flexibility (FLEX) of
residues of a target amino acid sequence. This information may be used in three
dimensional structure prediction approaches as a way to reduce the conformational
search space. The proposed method was tested with 24 different amino acid
sequences. Evolving neural networks were compared against a traditional error
back-propagation algorithm; results show that the proposed method is a powerful
way to extract and represent structural information from protein molecules that
are determined experimentally.
PMID- 28403669
TI - Use of videoconferencing for physical therapy in people with musculoskeletal
conditions: A systematic review.
AB - Background Physical therapists are key players in the management of
musculoskeletal conditions, which are common in rural and remote communities.
There are few physical therapists in rural regions compared to potential need, so
care is either not provided or must be sought in urban centers, requiring travel
and time away from work and family to access services. Telerehabilitation
strategies, such as real-time videoconferencing, are emerging as possible
solutions to address shortages in rural physical therapy services. Objectives
This review will: (1) determine the validity and the reliability of secure
videoconferencing for physical therapy management of musculoskeletal conditions;
(2) determine the health, system, and process outcomes when using secure
videoconferencing for physical therapy management of musculoskeletal conditions.
Methods A protocol-driven systematic review of four databases was carried out by
two independent reviewers. Study criteria included English language articles from
January 2003 to December 2016, on physical therapy management using secure
videoconferencing, pertaining to adults 18-80 years with chronic musculoskeletal
disorders. Randomized controlled trials, pre-experimental studies, and case
control studies were included. Quality analysis was performed utilizing
standardized tools specific for the study designs. Results and conclusions
Validity and reliability studies were identified as having high risk of bias.
Intervention studies were of moderate quality, and found positive impact on
health outcomes and satisfaction. Two studies evaluated costs, with evidence of
cost savings in one study. More robust research is required to evaluate long-term
effects of telerehabilitation for physical therapy management of musculoskeletal
disorders, including cost-benefit analyses.
PMID- 28403671
TI - Erratum.
PMID- 28403670
TI - Genetic variants in FH are associated with renal histopathologic subtypes of
lupus nephritis: a large cohort study from China.
AB - Objective Genetic variants in FH (complement factor H) were reported to associate
with susceptibility to systemic lupus erythematosus (SLE). This study proposed
that the genetic defects of FH in the susceptibility and in the development of
lupus nephritis might be different. Methods This study enrolled 334 lupus
nephritis patients, 269 SLE patients without clinical renal involvement and 350
controls. Two-step genotyping was performed. First, all the exons of the FH gene
were fully sequenced in 100 lupus nephritis patients and 100 healthy controls.
Second, genotyping of three common variants reported to be functional, rs1061170,
rs800292 and rs6677604, was conducted in all the recruited individuals. Further,
analysis of their associations with SLE/lupus nephritis susceptibility and the
clinico-pathological parameters in the lupus nephritis group was performed.
Results No significant differences were observed in allele and genotype
frequencies of the three single nucleotide polymorphisms between lupus patients
and controls. There was a significantly higher ratio of CC/CT genotypes of
rs1061170 in lupus nephritis patients with class III than in the other two
classes (class III vs. class IV vs. class V: 21.0% vs. 9.7% vs. 9.4%; P = .044).
The rs6677604-GG genotype was observed to be associated with the absence of anti
ds DNA antibody ( P = .021), and the rs800292-TT genotype was associated with a
higher level of circulating C3 ( P = 0.20) in lupus nephritis. Conclusion In an
independent cohort, this is the first genetic association analysis focusing on FH
genetic variants in Chinese lupus nephritis patients. It was found that the
variants in the FH gene might affect the histopathologic subtypes and some
clinical features of the disease.
PMID- 28403672
TI - Toxic megacolon as a rare complication following atropine therapy due to
organophosphate poisoning: A case report.
AB - The main therapeutic basis for a case of organophosphate poisoning is a
combination therapy which includes atropine as an anticholinergic drug and
pralidoxime. If the poisoning is severe, a high dose of this combination of
medicines may be needed, but this may cause serious side effects: paralytic ileus
or even megacolon; however, these gastrointestinal events are very rare. Here, we
report a case of organophosphate poisoning where atropine therapy was given and
led to drug-associated toxic megacolon.
PMID- 28403674
TI - Haemoglobin site-specifically modified with ferulic acid to suppress the
autoxidation.
AB - Haemoglobin site-specifically modified with ferulic acid (FA-Hb), was
synthesized. The effects on the characteristic absorption and the oxygen
saturation curve of FA-Hb were investigated by UV-Vis spectrophotometry and
oxygen analyzer. Furthermore, the autoxidation rates of Hb and FA-Hb were also
discussed with or without sodium azide in the system. The results showed that
there was no obvious transformation of the heme structure of FA-Hb. It was also
demonstrated that the oxygen-carrying capacity of FA-Hb was similar to the
natural Hb, but the autoxidation rate of FA-Hb was much lower than Hb in
different systems.
PMID- 28403673
TI - Mechanisms Mediating Functional Hyperemia in the Brain.
AB - Neuronal activity within the brain evokes local increases in blood flow, a
response termed functional hyperemia. This response ensures that active neurons
receive sufficient oxygen and nutrients to maintain tissue function and health.
In this review, we discuss the functions of functional hyperemia, the types of
vessels that generate the response, and the signaling mechanisms that mediate
neurovascular coupling, the communication between neurons and blood vessels.
Neurovascular coupling signaling is mediated primarily by the vasoactive
metabolites of arachidonic acid (AA), by nitric oxide, and by K+. While much is
known about these pathways, many contentious issues remain. We highlight two
controversies, the role of glial cell Ca2+ signaling in mediating neurovascular
coupling and the importance of capillaries in generating functional hyperemia. We
propose signaling pathways that resolve these controversies. In this scheme,
capillary dilations are generated by Ca2+ increases in astrocyte endfeet, leading
to production of AA metabolites. In contrast, arteriole dilations are generated
by Ca2+ increases in neurons, resulting in production of nitric oxide and AA
metabolites. Arachidonic acid from neurons also diffuses into astrocyte endfeet
where it is converted into additional vasoactive metabolites. While this scheme
resolves several discrepancies in the field, many unresolved challenges remain
and are discussed in the final section of the review.
PMID- 28403675
TI - Advances in the use of surgery and multimodality treatment for N2 non-small cell
lung cancer.
AB - INTRODUCTION: Stage IIIA-N2 non-small cell lung cancer (NSCLC) represents a
heterogeneous group of bronchogenic carcinomas with locoregional involvement.
Different categories of N2 disease exist, ranging from unexpectedly encountered
N2 involvement after detailed preoperative staging or 'surprise' N2, to
potentially resectable disease treated within a combined modality setting, and
finally, bulky N2 involvement treated by chemoradiation. Areas covered: Large
randomised controlled trials and meta-analyses on stage IIIA-N2 NSCLC have been
published but their implications for treatment remain a matter of debate. No
definite recommendations can be provided as diagnostic and therapeutic algorithms
vary according to local, national or international guidelines. Expert commentary:
From the literature, it is clear that patients with stage IIIA-N2 NSCLC should be
treated by combined modality therapy including chemotherapy, radiotherapy and
surgery. The relative contribution of each modality has not been firmly
established. For patients undergoing induction therapy, adequate restaging is
important as only down-staged patients will clearly benefit from surgical
resection. Each patient should be discussed within a multidisciplinary team to
determine the best diagnostic and therapeutic approach according to the specific
local expertise. In the near future, it might be expected that targeted therapies
and immunotherapy will be incorporated as possible therapeutic options.
PMID- 28403676
TI - An overview application of silver nanoparticles in inhibition of herpes simplex
virus.
AB - Nanoscale particles and molecules are a potential different for the treatment of
disease because they have distinctive biologic property based on their structure
and size, which is different from traditional small-molecule drugs. The
antimicrobial mechanisms of silver nanoparticles include the formation of free
radicals damaging the bacterial membranes, interactions with DNA, adhesion to
cell surface altering the membrane properties, and enzyme damage. In this review,
we focus on applications of silver nanoparticles in inhibition of herpes simplex
virus.
PMID- 28403677
TI - Spatial/Temporal Variations of Crime: A Routine Activity Theory Perspective.
AB - Temporal and spatial patterns of crime in Campinas, Brazil, are analyzed
considering the relevance of routine activity theory in a Latin American context.
We use geo-referenced criminal event data, 2010-2013, analyzing spatial patterns
using census tracts and temporal patterns considering seasons, months, days, and
hours. Our analyses include difference in means tests, count-based regression
models, and Kulldorff's scan test. We find that crime in Campinas, Brazil,
exhibits both temporal and spatial-temporal patterns. However, the presence of
these patterns at the different temporal scales varies by crime type.
Specifically, not all crime types have statistically significant temporal
patterns at all scales of analysis. As such, routine activity theory works well
to explain temporal and spatial-temporal patterns of crime in Campinas, Brazil.
However, local knowledge of Brazilian culture is necessary for understanding a
portion of these crime patterns.
PMID- 28403678
TI - 37th International Congress of the European Association of Poisons Centres and
Clinical Toxicologists (EAPCCT) 16-19 May 2017, Basel, Switzerland.
PMID- 28403679
TI - Levofloxacin-Induced Acute Immune-Mediated Thrombocytopenia of Rapid-Onset.
AB - Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient
has been receiving the implicated drug for at least 1 week, due to newly forming
drug-dependent antibodies ("typical-onset" D-ITP). A "rapid-onset" form of D-ITP
can occur when previous sensitization has occurred, where antibodies have thus
already been formed, and a precipitous platelet count fall occurs upon
reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the
rapid-onset form with a well-documented previous exposure has not been described.
We report a 76-year-old male treated with levofloxacin for acute exacerbation of
chronic obstructive pulmonary disease. After a single 750 mg oral dose of
levofloxacin, his platelet count fell from 187 to 5 * 109/L (nadir) over 4 days.
Other causes of thrombocytopenia were ruled out. He had received a previous
course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and
treatment with intravenous immunoglobulin and dexamethasone resulted in platelet
count recovery. Levofloxacin-dependent antibodies were not detectable, consistent
with the known low sensitivity of laboratory tests for drug-dependent antibodies,
presumably indicating antibodies against levofloxacin metabolites, as is
indirectly supported by the abrupt but relatively slow platelet count decline
observed. This case illustrates a rapid-onset presentation of levofloxacin
induced D-ITP in the setting of previous drug exposure.
PMID- 28403680
TI - Examining the relationship between child maltreatment and school performance in
public schools in Saudi Arabia: A pilot study.
AB - AIMS: The aim of this study was to examine the relationship between child
maltreatment (CM) and school performance among adolescents in Saudi Arabia.
METHODS: A cross-sectional study was conducted in Riyadh, Saudi Arabia, in 2014.
The enrolment criteria included both male and female Saudi students ( n=674;
52.7% male) aged 12-19 years ( Mage=15.6+/-1.6 years), attending intermediate and
secondary schools belonging to the Ministry of National Guard. A self
administered questionnaire was used to gather information on different forms of
abuse that had occurred in the past or were currently occurring. RESULTS: Poor
school performance was more likely in students who lived among substance-use
family members or guardians compared with those who did not (33.3% vs. 11.4%;
p<0.01), those with an imprisoned family member compared with those without
(26.5% vs. 11.2%; p<0.01), those who were psychologically abused compared with
those who were not abused (21.0% vs. 10.1%; p<0.01), those who were physically
abused compared with those who were not abused (18.9% vs. 9.3%; p<0.01), and
those suffering multiple forms of abuse compared with those not abused (23.4% vs.
9.7%; p<0.01). Logistic regression analysis showed that household dysfunction was
the most predisposing factor to poor performance in school, and included living
among substance-use family members or guardians (odds ratio=4.0; 95% confidence
interval=1.7-9.5) and living with imprisoned family member (odds ratio=3.1, 95%
confidence interval=1.5-6.3). CONCLUSIONS: CM, along with family structure and
dynamics, has an adverse relationship with students' school performance. These
findings highlight the importance of increasing awareness of the impact of CM on
school performance among families, schools and the community.
PMID- 28403681
TI - Atrophy, ultra-structural disorders, severe atrophy and degeneration of
denervated human muscle in SCI and Aging. Implications for their recovery by
Functional Electrical Stimulation, updated 2017.
AB - OBJECTIVES: Long-term lower motor neuron denervation of skeletal muscle is known
to result in degeneration of muscle with replacement by adipose and fibrotic
tissues. However, long-term survival of a subset of skeletal myofibers also
occurs. METHODS: We performed transverse and longitudinal studies of patients
with spinal cord injury (SCI), patients specifically complete Conus and Cauda
Equina Syndrome and also of active and sedentary seniors which included analyses
of muscle biopsies from the quadriceps m. RESULTS: Surprisingly, we discovered
that human denervated myofibers survive years of denervation after full and
irreversible disconnection from their motor neurons. We found that atrophic
myofibers could be rescued by home-based Functional Electrical Stimulation (h
bFES), using purpose developed stimulators and electrodes. Although denervated
myofibers quickly lose the ability to sustain high-frequency contractions, they
respond to very long impulses that are able to allow for re-emergence of tetanic
contractions. A description of the early muscle changes in humans are hampered by
a paucity of patients suffering complete Conus and Cauda Equina Syndrome, but the
cohort enrolled in the EU RISE Project has shown that even five years after SCI,
severe atrophic myofibers with a peculiar cluster reorganization of myonuclei are
present in human muscles and respond to h-bFES. CONCLUSIONS: Human myofibers
survive permanent denervation longer than generally accepted and they respond to
h-bFES beyond the stage of simple atrophy. Furthermore, long-term
denervation/reinnervation events occur in elderly people and are part of the
mechanisms responsible for muscle aging and again h-bFES was beneficial in
delaying aging decay.
PMID- 28403682
TI - The Ububele Baby Mat Service - A primary preventative mental health intervention
in a culturally diverse setting.
AB - The Ububele Baby Mat Service is a community-based, parent-infant mental health
intervention offered at five primary health care clinics in Alexandra Township,
in Johannesburg. The aim of the intervention is to promote healthy caregiver
infant attachments. There has been a steady increase in the number of mother-baby
dyads making use of the service. This paper aims to explore how the Baby Mat
Service and Baby Mat practitioners position and locate themselves in a culturally
diverse community setting where multiple meaning systems are drawn on for making
sense of health concerns. Two key components of the Baby Mat Service are
discussed: i) the presence of an inter-racial therapeutic couple on the mat; and
ii) the stance adopted by the Baby Mat practitioners in relation to culturally
diverse understandings of a presenting problem. The therapeutic couple engages
with culturally-informed frames of reference in an attitude of wondering and
tentative thinking ("mhlawumbe" in isiZulu). When a respectfully curious stance
was taken by practitioners, it was found to help those accessing the mat to find
symbolic meaning in the presenting problem and integrate this with cultural
understandings.
PMID- 28403683
TI - Whole-genome sequencing of Klebsiella pneumoniae MDR strain isolated in a Syrian
refugee.
PMID- 28403684
TI - Mangiferin prevents corticosterone-induced behavioural deficits via alleviation
of oxido-nitrosative stress and down-regulation of indoleamine 2,3-dioxygenase
(IDO) activity.
AB - BACKGROUND: In recent years, a substantial amount of experimental studies have
demonstrated that exogenous administration of corticosterone causes anxiety and
depressive-like behaviour in rodents which involves hypothalamic-pituitary
adrenal axis dysregulation. Our present study aimed to explore the
neuroprotective potential of mangiferin against corticosterone-induced anxiety
and depressive-like behaviour. METHODS: Corticosterone (40 mg/kg; subcutaneously)
was administered once daily in swiss albino mice for 21 days. Mice were treated
simultaneously with mangiferin (40 mg/kg; p.o.), 30 min prior to the
corticosterone injection. RESULTS: Chronic administration of corticosterone
caused anxiety and depressive-like behaviour in mice which was significantly
alleviated by mangiferin treatment. Biochemical analysis revealed that mangiferin
treatment significantly attenuated corticosterone-induced oxido-nitrosative
stress and neuroinflammation in the hippocampus region. Furthermore, concomitant
treatment with mangiferin significantly enhanced the hippocampal brain-derived
neurotrophic factor (BDNF) level and decreased the serum corticosterone level in
the corticosterone-treated animals. Western blotting analysis revealed that
corticosterone administration significantly up-regulated the indoleamine 2,3
dioxygenase (IDO) protein expression level in the hippocampus which was
significantly reduced by mangiferin treatment. CONCLUSION: Taken together, our
results suggest that mangiferin exerts anti-anxiety and antidepressant effect in
corticosterone-treated rats, which is probably mediated through up-regulation of
BDNF level along with inhibition of oxido-nitrosative stress, neuroinflammation
and IDO up-regulation in the hippocampus region.
PMID- 28403685
TI - Salivary Cortisol Responses and Session Ratings of Perceived Exertion to a Rugby
Match and Fatigue Test.
AB - This study compared the effects of an official rugby match and a fatigue test on
the salivary cortisol responses of 13 rugby players. We also examined the
relationship between this cortisol response and session ratings of perceived
exertion (session-RPE). We collected saliva before and after the match and
fatigue test and assessed physical effort intensity via session-RPE using a CR-10
scale. We measured cortisol concentration by enzyme-linked immunosorbent assays.
Results were greater session-RPE and cortisol concentrations for the rugby match,
compared with the fatigue test. There was a significant difference between
cortisol concentrations obtained pre- and postmatch ( p < .022) and significant
correlations between cortisol response and session-RPE sampling in both the rugby
match ( r = .81; p < .001) and fatigue test ( r = .91; p < .001). This study
provides evidence of greater perceived effort and higher cortisol concentrations
in actual competition versus a fatigue test. Our data further support session-RPE
as a relatively inexpensive close correlate of a stress biomarker (cortisol
response). Thus, session-RPE can be used by coaches as a valid indication of
training loads and adequate recovery time after exertion.
PMID- 28403686
TI - Swimming training induces liver adaptations to oxidative stress and insulin
sensitivity in rats submitted to high-fat diet.
AB - Oxidative stress, physical inactivity and high-fat (FAT) diets are associated
with hepatic disorders such as metabolic syndrome (MS). The therapeutic effects
of physical training (PT) were evaluated in rats with MS induced by FAT diet for
13 weeks, on oxidative stress and insulin signaling in the liver, during the last
6 weeks. FAT-sedentary (SED) rats increased body mass, retroperitoneal fat, mean
arterial pressure (MAP) and heart rate (HR), and total cholesterol, serum alanine
aminotransferase, glucose and insulin. Livers of FAT-SED rats increased
superoxide dismutase activity, thiobarbituric acid-reactive substances, protein
carbonyl and oxidized glutathione (GSSG); and decreased catalase activity,
reduced glutathione/GSSG ratio, and the mRNA expression of insulin receptor
substrate 1 (IRS-1) and serine/threonine kinase 2. FAT-PT rats improved in
fitness and reduced their body mass, retroperitoneal fat, and glucose, insulin,
total cholesterol, MAP and HR; and their livers increased superoxide dismutase
and catalase activities, the reduced glutathione/GSSG ratio and the expression of
peroxisome proliferator-activated receptor gamma and insulin receptor compared to
FAT-SED rats. These findings indicated adaptive responses to PT by restoring the
oxidative balance and insulin signaling in the liver and certain biometric and
biochemical parameters as well as MAP in MS rats.
PMID- 28403687
TI - Mechanochemical endovenous ablation of saphenous veins using the ClariVein: A
systematic review.
AB - Objective To systematically review all available English literature on
mechanochemical endovenous ablation and to report on the anatomical, technical,
and clinical success. Methods A systematic literature search was performed in
PubMed, EMBASE, and the Cochrane Library on mechanochemical endovenous ablation
for the treatment of insufficient great and/or small saphenous vein.
Methodological quality of the included studies was evaluated using the MINORS
score. The primary outcome measure was anatomical success, defined as closure of
the treated vein on follow-up duplex ultrasound imaging. Secondary outcomes were
technical and clinical success, and major complications defined as deep venous
thrombosis, pulmonary embolisms or paresthesia. Results The literature search
identified 759 records, of which 13 were included, describing 10 unique cohorts.
A total of 1521 veins (1267 great saphenous vein and 254 small saphenous vein)
were included, with cohort sizes ranging from 30 to 570 veins. The pooled
anatomical success rate after short-term follow up was 92% (95% CI 90-94%) ( n =
1314 veins). After 6 and 12 months these numbers were 92% (95% CI 88-95%) ( n =
284) and 91% (95% CI 86-94%) ( n = 228), respectively. The long-term anatomical
success rates at 2 and 3 years were 91% (95% CI 85-95%) ( n = 136) and 87% (95%
CI 75-94%) ( n = 48), respectively. Major complications and especially nerve
injury were very rare (<= 0.2%). All studies were of moderate or good quality
using the MINORS scoring scale. Conclusions Mechanochemical endovenous ablation
using the ClariVein in combination with liquid sclerosant is associated with an
anatomical success rate ranging from 87% to 92% and good clinical success. To
date, no randomized controlled trials are available studying the anatomical
success after mechanochemical ablation, compared to the endothermal ablation. The
risk of major complications is very low after the procedure.
PMID- 28403688
TI - Quantification of early cutaneous manifestations of chronic venous insufficiency
by automated analysis of photographic images: Feasibility and technical
considerations.
AB - We postulate that blue telangiectasia and brownish pigmentation at ankle level,
early markers of chronic venous insufficiency, can be quantified for longitudinal
studies of chronic venous disease in Caucasian people. Objectives and methods To
describe a photographic technique specially developed for this purpose. The
pictures were acquired using a dedicated photo stand to position the foot in a
reproducible way, with a normalized lighting and acquisition protocol. The image
analysis was performed with a tool developed using algorithms optimized to detect
and quantify blue telangiectasia and brownish pigmentation and their relative
surface in the region of interest. To test the short-term reproducibility of the
measures. Results The quantification of the blue telangiectasia and of the
brownish pigmentation using an automated digital photo analysis is feasible. The
short-term reproducibility is good for blue telangiectasia quantification. It is
a less accurate for the brownish pigmentation. Conclusion The blue telangiectasia
of the corona phlebectatica and the ankle flare can be assessed using a
clinimetric approach based on the automated digital photo analysis.
PMID- 28403689
TI - Limits, excesses and pleasures: practices and discourses of sex work in a Mexican
rural community.
AB - In Tomatlan, a small city on the Mexican Pacific Coast there is a tolerance zone
in which a group of sex workers, separated from the rest of the city by a garbage
dump, offer their services to local men. The women present themselves materially
and symbolically as agents of regulation with respect to male sexuality, itself
constructed as overwhelming and insatiable, which, were it not for services
provided by the sex workers, would threaten the family-based social order.
Through in-depth interviews with 19 sex workers and 5 municipal officials, this
paper discusses how the sex gender system results in a series of borders that are
both geographical and subjective. Such borders have to do with periphery and
control, body and intimacy, and the boundaries of animality.
PMID- 28403690
TI - Exploring the relationship between victims and witnesses of aggression and anger
expression in Thai adolescents.
AB - OBJECTIVE: Young people who are victims of, or witnesses to, aggression are at
increased risk of developing a psychological disorder and behaving aggressively
themselves. The aim of this study was to report the prevalence of exposure to
aggression in a sample of 1 770 students, aged 15-26 years recruited from
technical colleges in Thailand. METHOD: Self-report questionnaires were used to
assess the prevalence rates for both experiencing aggression as a victim and for
witnessing an aggressive incident. Logistic regression methods were then used to
examine the possible association between acting aggressively and being a victim
of, or a witness to, aggression. RESULTS: In the previous six months, over half
of all students reported being yelled at and had witnessed friends being hit.
Those students who reported 'being pushed' or 'being hit' themselves had higher
levels of anger expression. Being an indirect victim and witnessing aggression
were only weakly associated with anger expression. CONCLUSIONS: Adolescents in
Thailand experience high rates of victimisation and commonly witness aggression.
Being personally victimised was shown to be significantly related to a subsequent
expression of anger, suggesting that interventions to prevent direct
confrontation may help to reduce the likelihood of victims becoming perpetrators.
PMID- 28403691
TI - Novel NLRC4 Mutation Causes a Syndrome of Perinatal Autoinflammation With
Hemophagocytic Lymphohistiocytosis, Hepatosplenomegaly, Fetal Thrombotic
Vasculopathy, and Congenital Anemia and Ascites.
AB - Autoinflammatory diseases are caused by pathologic activation of the innate
immune system. Primary hemophagocytic lymphohistiocytosis (HLH) is an aggressive
syndrome of excessive immune activation caused by monogenic mutations resulting
in cytotoxic cell defects and subsequent failure to eliminate activated
macrophages. Secondary HLH is often diagnosed in cases without a known Mendelian
inheritance. However, some cases of "secondary" HLH have been shown to harbor
mutations with partial dysfunction of the cytotoxic system. Recently, macrophage
intrinsic abnormalities caused by NLRC4 inflammasome mutations have been linked
to autoinflammation and recurrent macrophage activation syndromes resembling a
primary HLH. We report a case of a former 28-week preterm infant with congenital
anemia, ascites, and a heavy edematous placenta with fetal thrombotic
vasculopathy, who developed hepatosplenomegaly and unexplained systemic
inflammation with laboratory features of HLH in the early postnatal course and
died at 2 months of age. Postmortem examination confirmed the hepatosplenomegaly
with marked sinusoidal hemophagocytosis, along with striking hemophagocytosis in
the bone marrow and lymph nodes. There was extensive acute and chronic ischemic
bowel disease with matted bowel loops, fibrous adhesions, and patchy necrotizing
enterocolitis features. Whole exome sequencing analysis demonstrated a novel
mosaic heterozygous NLRC4 512 C> T (p.Ser171Phe) de novo mutation predicated to
cause a dominant, gain-of-function mutation resulting in a constitutively active
protein. The assembly of NLRC4-containing inflammasomes via an induced self
propagation mechanism likely enables a perpetuating process of systemic
macrophage activation, presumed to be initiated in utero in this patient.
PMID- 28403692
TI - Severe hypokalemia due to a possible drug-drug interaction between vinblastine
and antiretrovirals in a HIV-infected patient with Hodgkin's lymphoma.
AB - A 60-year-old HIV-1 infected woman on antiretroviral therapy
(emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's
lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and
dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia.
Hypokalemia was considered as part of a proximal tubular renal dysfunction, and
other causes of hypokalemia were excluded. Due to suspicion of drug--drug
interactions between antiretrovirals and vinblastine, ritonavir-boosted
atazanavir was switched to dolutegravir and the patient continued
emtricitabine/tenofovir. In the subsequent ABVD cycles, no neutropenia or
hypokalemia were observed. Vinblastine is metabolized by the hepatic P450
cytochrome isoenzyme CYP3A4, therefore, concomitant administration with protease
inhibitors may increase plasma levels of vinblastine. Vinblastine is also a
substrate and inhibitor of multidrug resistance-associated protein 2 (MRP2)
transporter in the proximal renal tubule. Inhibition of this renal transporter
could increase tenofovir renal toxicity. Our hypothesis is that the hypokalemia
could be a result of a tenofovir-mediated tubular damage triggered by the
increased vinblastine serum levels secondary to a CYP3A4 inhibition by ritonavir.
To the best of our knowledge, this is the first report of severe hypokalemia and
proximal tubular renal dysfunction as a result of a possible drug-drug
interaction between vinblastine, tenofovir and ritonavir-boosted atazanavir.
PMID- 28403693
TI - Anterior retropharyngeal plate screw fixation with bilateral anterior
transarticular screws for odontoid fractures ... a new comprehensive technique.
AB - INTRODUCTION: A certain group of odontoid fractures (Anderson and D' Alonzo Type
2) are usually offered surgical treatment. Common surgical option is an anterior
odontoid screw. Some of the fractures are not suitable for anterior odontoid
screw (anterior oblique, displaced distal fragments and those with atlantoaxial
instability) and these are usually offered posterior transarticular screws
(Magerl's) or posterior atlantoaxial screw rod/plate fixation (Goel-Harms
technique). Posterior surgery involves atlantoaxial fixation with an indirect
attempt to reduce and fuse the fracture . Posterior surgery has a risk of injury
to the vertebral arteries, hemorrhage from the paravertebral venous plexus and
the C2 root ganglion. METHODS: A direct anterior submandibular retropharyangeal
approach with open reduction and fixation (ORIF) using a customized variable
screw placement (VSP) plate was used to realign and fix the fracture fragments in
compression mode under direct vision. Twenty patients of type-II odontoid
fractures (unsuitable for anterior odontoid screw) underwent an anterior
retropharyngeal approach with anterior variable screw position (VSP) plate and
screw fixation and eight amongst them, who had associated atlantoaxial
instability underwent additional bilateral anterior transarticular screws.
RESULTS: All patients treated by this technique had 100% fracture site bone union
without any implant failure. Longest follow-up has been for 3 years. CONCLUSION:
Anterior retropharyangeal approach allows direct fracture fragment realignment
under vision with an opportunity to fix in compression mode using the VSP plate,
which ensures early fusion across the type-II odontoid fracture. Any associated
instability can be treated by additional bilateral anterior transarticular
screws. The approach is simple and safe without any risk to the vertebral
arteries and biomechanically appealing.
PMID- 28403694
TI - Resilient memory for melodies: The number of intervening melodies does not
influence novel melody recognition.
AB - In many memory domains, a decrease in recognition performance between the first
and second presentation of an object is observed as the number of intervening
items increases. However, this effect is not universal. Within the auditory
domain, this form of interference has been demonstrated in word and single-note
recognition, but has yet to be substantiated using relatively complex musical
material such as a melody. Indeed, it is becoming clear that music shows
intriguing properties when it comes to memory. This study investigated how the
number of intervening items influences memory for melodies. In Experiments 1, 2
and 3, one melody was presented per trial in a continuous recognition paradigm.
After each melody, participants indicated whether they had heard the melody in
the experiment before by responding "old" or "new." In Experiment 4, participants
rated perceived familiarity for every melody without being told that melodies
reoccur. In four experiments using two corpora of music, two different memory
tasks, transposed and untransposed melodies and up to 195 intervening melodies,
no sign of a disruptive effect from the number of intervening melodies beyond the
first was observed. We propose a new "regenerative multiple representations"
conjecture to explain why intervening items increase interference in recognition
memory for most domains but not music. This conjecture makes several testable
predictions and has the potential to strengthen our understanding of domain
specificity in human memory, while moving one step closer to explaining the
"paradox" that is memory for melody.
PMID- 28403695
TI - Leprosy case detection campaign (LCDC) for active surveillance.
PMID- 28403696
TI - Congenital transmesenteric strangulated hernia in a neonate: a case report.
PMID- 28403697
TI - Cutaneous schistosomiasis: an uncommon location of a common disease.
PMID- 28403699
TI - Whistle Blowing and Ethics in Health and Social Care Ash Angie Whistle Blowing
and Ethics in Health and Social Care 184pp L17.99 Jessica Kingsley 9781849056328
1849056323 [Formula: see text].
AB - In view of recent high-profile cases of whistle blowing in the UK, this book is
valuable for novice and experienced practitioners.
PMID- 28403698
TI - High-risk neuroblastoma in a sub-Saharan African country: telling it like it is.
AB - Neuroblastoma is uncommon in Africa, but when seen usually presents as high-risk
disease with a poor prognosis. This aggressive biology of the tumour is
frequently augmented by delayed presentation. Current treatment depends upon
technologies and skills that are scarce in developing countries and the cost
involved is generally beyond the means of healthcare providers who are faced with
a myriad more pressing healthcare issues. The presentation, treatment and outcome
of 45 African children with neuroblastoma are described. Due to a lack of
resources precise risk stratification was impossible but visceral or bone
metastases were present in 73% of patients at diagnosis. In 91% the primary
tumour was intra-abdominal. Three children (7%) were paraplegic on admission. A
localised tumour was seen in one child (2%). Fifteen children (33%) underwent a
surgical procedure, with intent to cure in five among whom resection was
incomplete in three. For all other children, treatment was palliative using
chemotherapy with judicious use of radiotherapy. Thirteen children (29%) survived
longer than six months. Overall survival at three years was 4%.
PMID- 28403700
TI - Rapid Adult Nursing May Andree le Rapid Adult Nursing 136pp L20.99 Wiley
Blackwell 9781119117117 1119117119 [Formula: see text].
AB - Each chapter of this book on the clinical practice of nursing is well written and
to the point, making it accessible for nurses at all levels.
PMID- 28403702
TI - Bell's palsy: excluding serious illness in urgent and emergency care settings.
AB - Bell's palsy is a relatively benign condition that affects about 20 in every
100,000 patients a year, and in most cases the signs and symptoms resolve fully
within around six months. The defining characteristic of the condition is a
unilateral facial palsy, but this is also apparent in other conditions with a
more serious prognosis, including strokes, some viral infections and tumours.
This article reviews the literature on recognition of Bell's palsy, examines the
underlying pathology, and compares it with other conditions associated with
facial palsy. The article critically analyses the evidence and guidelines to
identify best practice, and considers areas for improvement. Finally, it
discusses how this information can be incorporated into practice, and provides
guidance for clinicians on differentiating between conditions in which patients
present with facial palsy to ensure they are managed appropriately.
PMID- 28403701
TI - Education must evolve to equip students for reality.
AB - Any emergency nurse (EN) will tell you that their learning truly began the day
they first started work in an emergency department (ED). Despite all the training
during a nursing degree course, it is only when an EN is exposed to the waiting
room or the ambulance bay of the ED that they can start relating clinical theory
to the reality of injured and sick adults and children at their most vulnerable.
PMID- 28403703
TI - 'Treat patients like family'.
AB - Why did you become an emergency nurse? I used to work as a healthcare assistant
and did bank shifts in the emergency department (ED). While there, I was drawn to
the unpredictable nature of the work, the challenge of delivering high-quality
care in a chaotic environment. No matter what your role is, you are an important
component of the emergency team. The resourcefulness of the nursing staff
impressed me and I thought 'I want to do that'.
PMID- 28403705
TI - Learning is everyone's responsibility.
AB - With the pressures of delivering high-quality care to the increasing number of
patients accessing emergency and urgent care, it is often difficult to ensure
that we continue to learn and develop.
PMID- 28403704
TI - Nursing management of reflex anoxic seizures in children.
AB - Children who present with transient loss of consciousness (T-LOC) are often first
seen in emergency departments (EDs). Reflex anoxic seizure (RAS), vasovagal
syncope and prolonged respiratory apnoea are benign, syncopal events that can be
generally managed by explanation and reassurance. RAS is a short, paroxysmal,
self-reverting episode of asystole that is triggered by pain, fear or anxiety and
is caused by increased vagal response. It is an important differential diagnosis
in pre-school age children who present with T-LOC, but is often underdiagnosed
and can sometimes be misdiagnosed as epilepsy. Nurses working in EDs are among
the first healthcare professionals to see children in acute settings and should
therefore be aware of RAS, the presenting features and management options. This
article discusses the epidemiology, pathophysiology and management of RAS,
includes an illustrative case study and discusses the role of ED nurses.
PMID- 28403707
TI - From twitter.
AB - Nurses on Twitter.
PMID- 28403706
TI - Is there a fairer way to evaluate capability?
AB - The objective structured clinical examination (OSCE) is a popular form of
assessment in clinical practice and higher education.
PMID- 28403708
TI - New standards set for young people.
AB - New standards have been set to address the rising number of children and young
people attending emergency departments.
PMID- 28403709
TI - Is credentialing a solution to the workforce crisis?
AB - With the number of patient attendances increasing, we need to address the
challenges facing the emergency care workforce, particularly how the system can
survive the shortage of doctors. It is a strategic priority for Health Education
England (HEE) to ensure an emergency care workforce with the right numbers,
skills and behaviours, that can respond to the changing patterns of service.
PMID- 28403710
TI - NICE Guidance.
AB - Healthcare professionals can now access guidance from the National Institute for
Health and Care Excellence (NICE) from smart devices.
PMID- 28403713
TI - Correction.
AB - In March's Emergency Nurse, the article on pre-hospital assessment of a child
under one year old with fever advised the administration of glucose if children
are 'very unwell or unconscious'. This should read 'check blood glucose'. We
apologise for the error and any inconvenience it has caused. A corrected version
is available online here .
PMID- 28403715
TI - Job satisfaction low in ambulance trusts.
AB - Staff at ambulance trusts have painted a bleak picture of their work experiences,
revealing high dissatisfaction over pay, staffing levels and the incidence of
work-related injuries.
PMID- 28403716
TI - Students teach children to stay safe at home.
AB - Primary school children in Greater Manchester have been learning accident
prevention skills with the help of nursing students from the University of
Salford.
PMID- 28403717
TI - Figuring out emergency care provision.
AB - Essential facts [Figure: see text] A national system to improve the recording of
how and what urgent and emergency care is provided is being introduced later this
year.
PMID- 28403718
TI - Early recognition of encephalitis in acute settings.
AB - Encephalitis is a life-threatening condition in which inflammation of the brain
tissue occurs. Although it is relatively rare, misdiagnosis or delays in
recognition and treatment can have devastating consequences for patients, and
there is a high mortality rate. People who survive are often left with
neuropsychological impairment. This article describes the pathophysiology of the
condition, as well as clinical presentation and treatment, and explains why it
can be easily missed. It includes a case study that describes a situation in
which the condition was not considered initially as a differential diagnosis, and
considers implications for practice.
PMID- 28403719
TI - Setting the bar.
AB - Amy Cawthorne, an advanced clinical practitioner in emergency care in Leeds, is
one of the first emergency nurses in the country to reach a national standard for
her role.
PMID- 28403720
TI - Call for return to four-hour target.
AB - Getting emergency care back on track was the first of four 'real priorities'
highlighted by the health secretary last month at the chief nursing officer for
England's summit.
PMID- 28403721
TI - NHS England promises to prioritise emergency care.
AB - Emergency care has been identified as one of four priorities by NHS England chief
executive Simon Stevens. The others are cancer care, general practice and mental
health care.
PMID- 28403722
TI - New formula to help staff reckon weight of patients.
AB - Researchers have proposed a simple formula for calculating the weight of adults
and adolescents in the emergency department (ED).
PMID- 28403724
TI - Emergency department doctors underestimate distress and pain.
AB - Children's pain is more accurately assessed by parents and the children
themselves than by emergency department (ED) doctors, who underestimate distress
levels, a Norwegian study concludes.
PMID- 28403725
TI - Clock ticking again on four-hour target.
AB - Emergency departments (EDs) in England have been told they need to start hitting
the four-hour target again by March 2018. Health secretary Jeremy Hunt has set
the deadline following the announcement of extra money in the Budget.
PMID- 28403726
TI - Gastrocnemius recession: A cadaveric study of surgical safety and effectiveness.
AB - Background and purpose - Many methods of gastrocnemius lengthening have been
described, with different surgical challenges, outcomes, and risks to the sural
nerve. Our aims were (1) to locate the gastrocnemius muscular-tendinous junction
in relation to the mid-length of the fibula (from here on designated the mid
fibula), (2) to compare the dorsiflexion achieved with dorsal recession or
ventral recession, and (3) to determine the risk of injury to the sural nerve
during gastrocnemius recession. Methods - In 10 pairs of fresh-frozen adult
cadaveric lower extremities transected above the knee, we measured dorsiflexion,
performed dorsal or ventral gastrocnemius recession at the mid-fibula, and then
measured the increase in dorsiflexion and fasciotomy gap. We noted the course of
the sural nerve and whether the gastrocnemius muscle provided it with enough
muscular coverage to protect it during recession. Results - Dorsal and ventral
recession produced statistically (p < 0.05) and clinically significant mean
increases in dorsiflexion with extended knee from 12 degrees to 19 degrees , but
they were not statistically significantly different from each other in this
measure or in fasciotomy gap size. At the mid-fibula, the sural nerve coursed
superficially between both heads of the gastrocnemius muscle in 14 of 20
specimens. Sufficient gastrocnemius muscle coverage to protect the sural nerve
was provided by the medial head in 18 of 20 specimens and by the lateral head in
only 5 of 20 specimens. Interpretation - A ventral gastrocnemius recession
proximal to the mid-fibula level poses less risk to the sural nerve than a
recession at the mid-fibula. This procedure provides adequate lengthening (1-3
cm) and increased dorsiflexion (compared with baseline), with less risk to the
sural nerve than is incurred with recession at the mid-fibular reference line.
PMID- 28403727
TI - High-risk human papillomavirus types in HIV-infected and HIV-uninfected young
women in KwaZulu-Natal, South Africa: implications for vaccination.
AB - BACKGROUND: High-risk human papillomavirus (hr-HPV) infections and low-grade
squamous intraepithelial lesions occur frequently in young women. The available
vaccines cover up to seven hr-HPV genotypes (HPV16, HPV18, HPV31, HPV33, HPV45,
HPV52 and HPV58) and two low-risk HPV types (HPV6 and HPV11). The objective of
this study was to describe the hr-HPV genotypes present among HIV-uninfected and
HIV-infected young women in rural high schools. METHODS: Cervicovaginal lavages
were obtained from sexually active young women recruited from high schools in
KwaZulu-Natal (n = 1223). HPV testing was done by the polymerase chain reaction
using GP5+/GP6 + primers and enzyme immunoassay. HIV testing was done using rapid
test kits. RESULTS: Of the 1223 cervicovaginal lavages, 301 (25%) were positive
for hr-HPV. The HPV prevalence was higher in HIV infected (32.20%, 95% CI: 0.27
0.38) than in HIV-uninfected women (22.50%, 95% CI: 0.21-0.26), (p = .001).
Similarly, multiple infections were slightly more common in HIV infected (59.32%)
than in HIV-uninfected women (53.51%), (p = .37). The nine predominant genotypes
in descending order were HPV types 16 (n = 99, 22.10%), 51 (n = 58, 12.91%), 18
(n = 56, 12.50%), 35 (n = 50, 11.10%), 33 (n = 47, 10.82%), 56 (n = 42, 9.31%),
45 (n = 34, 7.60%), 52 (n = 32, 7.14%) and 59 (n = 31, 6.91%). HPV 35, 51, 56 and
59 (40.62%), which are not covered by any vaccine, were among the most prevalent
in the schools of KwaZulu-Natal. CONCLUSION: Four of the most predominant high
risk HPV types in this region are not covered by the new nine-valent HPV vaccine.
PMID- 28403728
TI - Analysis of the implementation of a personalized care model in diabetes mellitus
as an example of chronic disease with information and communication technology
support.
AB - INTRODUCTION: Diabetes mellitus affects 13.8% of the adult population in Spain,
representing some 8.2% of total Spanish health spending, which may be reduced by
optimizing treatment and disease monitoring. Areas covered: This perspective
article aims to evaluate the possible clinical and economic outcomes of
implementing a theoretical personalized care model in diabetes supported by
information and communications technology in Spain vs. conventional care.
Moreover, we assessed the value of emminens(r) eConecta, a solution designed to
support the operational implementation of this model, which enables the
connection and participation of patients and health professionals, facilitates
patient education, decision-making, access to information, and data analysis. We
carried out a review of the available evidence, consultations with experts and a
clinical and cost estimation. Expert commentary: The experts consulted considered
that the proposed model is consistent with Spanish strategies on chronicity,
supports the management of chronicity/diabetes, and may improve the most
important aspects of disease management. In the literature, this type of care
models improved or provided equal disease control compared with conventional
care, potentiated self-management strategies and reduced the high use of
resources. Cost estimation showed a reduction of -12% in total direct costs and
around -34% in the costs of outpatient visits.
PMID- 28403733
TI - Health and Safety at the Dawn of the Trump Administration.
PMID- 28403729
TI - Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in
Brazil; findings and implications.
AB - INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4,
indicated for the treatment of type 2 diabetes mellitus, combined or not with
metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in
the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and
CRD, six studies were selected for the economic models. This study utilised cost
data in the Brazilian health system to provide the context. Expert commentary:
Type 2 diabetes mellitus is an epidemic disease and represents a challenge for
all health care systems. Although guidelines clearly define first-line treatment,
there are several other promising treatments. Vildagliptin is one of them,
resulting in a mean lifetime increase of 0.31 years compared to metformin alone
and 1.19 more life years compared to other metformin combinations. Considering
observational data, life years with dual vildagliptin-containing treatments were
0.37 more compared to other dual treatments. However, its high cost versus
generic metformin and its unclear safety profile weakens its subsequent cost
effectiveness. Consequently, the incorporation of vildagliptin or its combination
with metformin is currently not recommended for the Brazilian Health Care System.
This may change as more data becomes available.
PMID- 28403734
TI - Steve B. Wing.
PMID- 28403735
TI - Undergraduate Environmental Public Health Education.
AB - Environmental, occupational, and public health in the United States are practiced
across a fragmented system that makes work across those areas more difficult. A
large proportion of currently active environmental and occupational health
professionals, advocates, policy makers, and activists are nearing retirement
age, while some of our major health challenges are heavily influenced by aspects
of environment. Concurrently, programs that educate undergraduate college
students in environmental health are faced with multiple, often competing demands
which can impede progressive movement toward dynamic curricula for the needs of
the twenty-first century. We describe our use of developmental evaluation to
negotiate these challenges in our specific undergraduate education program, with
the dual aims of drawing attention to developmental evaluation as a useful tool
for people involved in environmental and occupational health advocacy, policy
making, activism, research, or education for change, as well as to promote
discussion about how best to educate the next generation of environmental public
health students.
PMID- 28403736
TI - Make Health and Safety a Part of Global Struggles Against Imperialism, Racism,
and Other Oppressions.
AB - Deborah "Deeg" Gold was presented in November 2016 with the Alice Hamilton Award
of the Occupational Health and Safety Section of the American Public Health
Association. Deeg worked for more than 20 years for the California Division of
Occupational Safety and Health (Cal/OSHA) as a field compliance officer, senior
industrial hygienist, and then became the agency's Deputy Chief for Health. Prior
to joining Cal/OSHA, Deeg Gold was a rank-and-file worker health and safety
activist in her union. She is also an activist on many social justice issues,
including opposing the death penalty and is a queer activist. This article is
Deeg's award acceptance speech.
PMID- 28403737
TI - Comparing Online and In-Person Delivery Formats of the OSHA 10-Hour General
Industry Health and Safety Training for Young Workers.
AB - Seven school districts or comprehensive high schools were enrolled in online OSHA
10-hour General Industry or Construction health and safety training via
CareerSafe to determine the feasibility of online training for students, given
limited resources for in-person trainings. A two-campus school district was
analyzed comparing OSHA 10 for General Industry across in-person, supervisor
level teachers as authorized trainers, and online course formats. The online
training courses were completed by 86 of 91 students, while another 53 of 57
students completed in-person training. Both groups completed identical OSHA
approved quizzes for "Introduction to OSHA," the initial 2-h module consistently
provided in OSHA 10 courses across topics and formats. Results indicated teacher
supervision was critical, and girls had higher online course completion rates,
overall quiz scores, and never failed. Though both cohorts passed, in-person had
significantly higher scores than online; both struggled with two questions.
Online OSHA 10 for General Industry can be an efficient learning tool for
students when limited resources prevent widespread availability of in-person
courses.
PMID- 28403738
TI - A Critique of Risk Disclosure as the Solution for Minimizing Toxic Exposures in
Pregnancy.
AB - The issue of pregnant women's exposures to everyday chemicals and the
implications for the health of future children are receiving increased attention
in popular media and in the academic press. In response, health profession
organizations are developing clinical practice guidelines for warning pregnant
women about the risks associated with exposures to certain toxics. We evaluate
different sides of a risk-avoidance approach for pregnant women in the context of
a hypothetical case study involving phthalates and women who work in nail salons.
We consider the ubiquitous nature of low-dose exposures and both the positive
aspects and limitations of promoting avoidance measures with respect to phthalate
exposures. We conclude that a risk-disclosure approach has both practical
limitations and equity dimensions which must be factored in to public health
guidelines and messaging and the development of clinical practice guidelines.
Upstream solutions including regulatory action on chemicals and heightened
attention to environmental justice would result in optimal management of this
issue.
PMID- 28403739
TI - Hydrogen Peroxide and Lipopolysaccharide Differentially Affect the Expression of
MicroRNAs 10a, 33a, 21, 221 in Endothelial Cells Before and After Coculture With
Monocytes.
AB - Inflammation and oxidative stress are important risk factors affecting various
cells in the formation of atherosclerosis. MicroRNAs (miRs) are regulators of
inflammation and atherogenesis. The expressions of endothelial cell (EC)-specific
miR-10a and miR-21 and monocyte-specific miR-33a and miR-221 were investigated
using coculture of the ECs and monocytes upon exposure to H2O2 as an oxidative
stressor, and endotoxin/lipopolysaccharide (LPS) as a microbial stressor. Human
umbilical endothelial cells (HUVECs) and peripheral blood mononuclear cells (or
monocytes) were cocultured in M199 complete medium and were incubated with LPS
(20 ng/mL) or H2O2 (1%) for 8 hours at 37 degrees C. The HUVECs and monocytes
were then separated from the cellular mix using a magnetic bead negative
selection technique. The relative expression of miRs was determined by real-time
polymerase chain reaction. In both cell types, H2O2 induced miR10a ( P = 0.05)
and LPS induced miR21 ( P = 0.0003) compared to the untreated controls. Coculture
increased miR-10a and miR-21 expression in monocytes ( P = 0.0008 and <0.0001);
however when cultured alone, HUVECs expressed higher levels of miR-10a and miR-21
( P < 0.0001 and <0.0001). Coculture decreased the expression of miR-33a in
monocytes ( P < 0.0001) while increasing miR221 in HUVECs and monocytes ( P <
0.0001 and <0.0001). The expression pattern of miRs in HUVECs and monocytes
changes in the coculture compared to culturing alone in response to oxidative and
microbial toxic compounds. Moreover, different cellular stressors induce
different athero-miRs, which may affect the course of inflammation.
PMID- 28403740
TI - Bisphenol A Induces Oxidative Stress in Bone Marrow Cells, Lymphocytes, and
Reproductive Organs of Holtzman Rats.
AB - Bisphenol A (BPA) is an estrogenic chemical used in the production of
polycarbonate plastics and epoxy resins. Our earlier studies have demonstrated
that BPA is a potent reproductive and genotoxic agent and affects the normal
physiological functions. The objective of this study was to evaluate whether
exposure to BPA induces oxidative stress. The male Holtzman rats were orally
gavaged with BPA (0.01 mg and 5.0 mg/kg/bw) over the period of 6 days. Animals
were euthanized by cervical dislocation at the end of the treatments; bone marrow
cells and blood lymphocytes were aspirated; testis and epididymis were collected,
immediately frozen in liquid nitrogen, and stored at -80 degrees C. These samples
were utilized for the determination of lipid peroxidation and various antioxidant
enzymes such as superoxide dismutase, catalase, and nonenzymatic reduced
glutathione. The results demonstrated that BPA caused an increase in lipid
peroxidation and a decrease in activity of various enzymatic and nonenzymatic
antioxidants in bone marrow cells, blood lymphocytes, and testicular and
epididymal tissues. The findings of the current study suggest that BPA exposure
induced oxidative stress, which could be one of the possible mechanisms causing
reproductive and genetic toxicity.
PMID- 28403741
TI - Impact of Acrylamide on Calcium Signaling and Cytoskeletal Filaments in Testes
From F344 Rat.
AB - Acrylamide (AA) at high exposure levels is neurotoxic, induces testicular
toxicity, and increases dominant lethal mutations in rats. RNA-sequencing in
testes was used to identify differentially expressed genes (DEG), explore AA
induced pathway perturbations that could contribute to AA-induced testicular
toxicity and then used to derive a benchmark dose (BMD). Male F344/DuCrl rats
were administered 0.0, 0.5, 1.5, 3.0, 6.0, or 12.0 mg AA/kg bw/d in drinking
water for 5, 15, or 31 days. The experimental design used exposure levels that
spanned and exceeded the exposure levels used in the rat dominant lethal, 2
generation reproductive toxicology, and cancer bioassays. The time of sample
collection was based on previous studies that developed gene expression-based
BMD. At 12.0 mg/kg, there were 38, 33, and 65 DEG ( P value <.005; fold change
>1.5) in the testes after 5, 15, or 31 days of exposure, respectively. At 31
days, there was a dose-dependent increase in the number of DEG, and at 12.0
mg/kg/d the top three functional clusters affected by AA exposure were actin
filament organization, response to calcium ion, and regulation of cell
proliferation. The BMD lower 95% confidence limit using DEG ranged from 1.8 to
6.8 mg/kg compared to a no-observed-adverse-effect-level of 2.0 mg/kg/d for male
reproductive toxicity. These results are consistent with the known effects of AA
on calcium signaling and cytoskeletal actin filaments leading to neurotoxicity
and suggest that AA can cause rat dominant lethal mutations by these same
mechanisms leading to impaired chromosome segregation during cell division.
PMID- 28403742
TI - Editor's Note.
PMID- 28403743
TI - Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.
AB - BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor
tissue to enable more complete and precise surgical resection. It is composed of
a chlorotoxin peptide covalently bound to the near-infrared fluorophore
indocyanine green. BLZ-100 is in clinical development for intraoperative
visualization of human tumors. The nonclinical safety and pharmacokinetic (PK)
profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates
(NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and
no adverse changes were observed in cardiovascular safety pharmacology, PK, and
toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect
levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP,
corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area
under-the-curve exposure values of 130 000 and 1 240 000 h.ng/mL, respectively.
Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and
monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies
(lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not
dose related. In a follow-up study in dogs, plasma histamine concentrations were
increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of
hypersensitivity, supporting the conclusion that the reactions were histamine
based. Hypersensitivity reactions were not observed in other species or in BLZ
100 human clinical studies conducted to date. The combined imaging, safety
pharmacology, PK, and toxicology studies contributed to an extensive initial
nonclinical profile for BLZ-100, supporting first-in-human clinical trials.
PMID- 28403746
TI - Feed-Forwardness of Spinal Networks in Posture and Locomotion.
AB - We present a new perspective on the concept of feed-forward compared to feedback
mechanisms for motor control. We propose that conceptually all sensory
information in real time provided to the brain and spinal cord can be viewed as a
feed-forward phenomenon. We also propose that the spinal cord continually adapts
to a broad array of ongoing sensory information that is used to adjust the
probability of making timely and predictable decisions of selected networks that
will execute a given response. One interpretation of the term feedback
historically entails responses with short delays. We propose that feed-forward
mechanisms, however, range in timeframes of milliseconds to an evolutionary
perspective, that is, "evolutionary learning." Continuously adapting events
enable a high level of automaticity within the sensorimotor networks that mediate
"planned" motor tasks. We emphasize that either a very small or a very large
proportion of motor responses can be under some level of conscious vs automatic
control. Furthermore, we make a case that a major component of automaticity of
the neural control of movement in vertebrates is located within spinal cord
networks. Even without brain input, the spinal cord routinely uses feed-forward
processing of sensory information, particularly proprioceptive and cutaneous, to
continuously make fundamental decisions that define motor responses. In effect,
these spinal networks may be largely responsible for executing coordinated
sensorimotor tasks, even those under normal "conscious" control.
PMID- 28403747
TI - Prevalence and predictors of suicidal ideations and attempts among homeless
children and adolescents in Ghana.
AB - OBJECTIVE: This study aimed to determine the prevalence and risk factors
associated with suicidal ideations and attempts among a sample of homeless street
children and adolescents found in Accra, Ghana. METHODS: A cross-sectional survey
of a convenience sample of 227 (122 male and 105 female) homeless youth was
conducted in Ghana. An interviewer-administered questionnaire was used to collect
data due to a low level of literacy among the study population. Bivariate and
multivariate logistic regressions were fitted to analyse the data. RESULTS: The
results indicated that 26.4% and 26.0% of the participants had attempted suicide
and reported suicidal ideations respectively. The multivariate logistic
regression showed that smoking, past and present use of alcohol, use of
marijuana, and engagement in prostitution, were associated with suicidal
ideations and suicide attempts. Suicidal ideations were associated with having
been physically beaten, robbed, and assaulted with a weapon; while a suicide
attempt was predicted by having been robbed and physically beaten. CONCLUSION:
This study increased our understanding of the determinants of suicidal ideations
and attempts among homeless youth. These findings suggest urgency to up-skill
mental health workers to assess for risk factors and offer pathways to care for
this vulnerable group.
PMID- 28403748
TI - An Effective Method of Atelocollagen Type 1/3 Isolation from Human Placenta and
Its In Vitro Characterization in Two-Dimesional and Three-Dimensional Cell
Culture Applications.
AB - Pepsin-solubilized atelocollagen can be used to form highly complex three
dimensional matrices for a broad spectrum of tissue engineering applications.
Moreover, it has a long history as a favorable biomaterial in pharmaceutical and
medical industries. So far, the main sources for these approaches are collagens
from xenogenic sources. Yet, these nonhuman collagens carry a risk of provoking
immune reactions in patients. Here we describe an effective method of isolating
atelocollagen type 1/3 (COL1/3) from human placenta. By combining a single pepsin
digestion step with tangential flow filtration and further precipitation steps,
we could purify COL1/3 within only 4 days of processing. The resulting COL1/3 was
biochemically characterized by determining residual DNA content, proving the
absence of impurities by sodium dodecyl sulfate/polyacrylamide gel
electrophoresis (SDS-PAGE) analysis combined with total amino acid
quantification, identifying the isolated collagen types by Western blot analysis,
and analyzing the spontaneous formation of fibrous structures on freeze-drying
via scanning electron microscopy. Finally, the cytocompatibility of the isolated
collagen was demonstrated in two dimensional using primary rat hepatocytes and in
three dimensional by a sprouting assay of human umbilical vein endothelial cell.
The isolation method described not only fulfills demands for cost-efficient
bioengineering using a human waste material but also potentially increases
overall safety for patients by use of homologous products.
PMID- 28403749
TI - Cluster success: fMRI inferences for spatial extent have acceptable false
positive rates.
AB - In an editorial (this issue), I argued that Eklund, Nichols, and Knutsson's 'null
data' reflected resting-state/default network activity that inflated their false
positive rates. Commentaries on that paper were received by Nichols, Eklund, and
Knutsson (this issue), Hopfinger (this issue), and Cunningham and Koscik (this
issue). In this author response, I consider these commentaries. Many issues
stemming from Nichols et al. are identified including: (1) Nichols et al. did not
provide convincing arguments that resting-state fMRI data reflect null data. (2)
Eklund et al. presented one-sample t-test results in the main body of their paper
showing that their permutation method was acceptable, while their supplementary
results showed that this method produced false-positive rates that were similar
to other methods. (3) Eklund et al. used the same event protocol for all the
participants, which artifactually inflated the one-sample t-test false-positive
rates. (4) At p < .001, using two-sample t-tests (which corrected for the flawed
analysis), all the methods employed to correct for multiple comparisons had
acceptable false-positive rates. (5) Eklund et al. contrasted resting-state
periods, which produced many significant clusters of activity, while null data
should arguably be associated with few, if any, significant activations. Eklund
et al.'s entire set of results show that commonly employed methods to correct for
multiple comparisons have acceptable false-positive rates. Following Hopfinger
along with Cunningham and Koscik, it is also highlighted that rather than
focusing on only type I error, type I error and type II error should be balanced
in fMRI analysis.
PMID- 28403750
TI - Improvement of the classification quality in detection of Hashimoto's disease
with a combined classifier approach.
AB - The purpose of the study was to construct an efficient classifier that, along
with a given reduced set of discriminant features, could be used as a part of the
computer system in automatic identification and classification of ultrasound
images of the thyroid gland, which is aimed to detect cases affected by
Hashimoto's thyroiditis. A total of 10 supervised learning techniques and a
majority vote for the combined classifier were used. Two models were proposed as
a result of the classifier's construction. The first one is based on the K
nearest neighbours method (for K = 7). It uses three discriminant features and
affords sensitivity equal to 88.1%, specificity of 66.7% and classification error
at a level of 21.8%. The second model is a combined classifier, which was
constructed using three-component classifiers. They are based on the K-nearest
neighbours method (for K = 7), linear discriminant analysis and a boosting
algorithm. The combined classifier is based on 48 discriminant features. It
allows to achieve the classification sensitivity equal to 88.1%, specificity of
69.4% and classification error at a level of 20.5%. The combined classifier
allows to improve the classification quality compared to the single model. The
models, built as a part of the automatic computer system, may support the
physician, especially in first-contact hospitals, in diagnosis of cases that are
difficult to recognise based on ultrasound images. The high sensitivity of
constructed classification models indicates high detection accuracy of the sick
cases, and this is beneficial to the patients from a medical point of view.
PMID- 28403751
TI - Management of dengue in Australian travellers: a retrospective multicentre
analysis.
AB - OBJECTIVES: To describe the epidemiology, clinical and laboratory features and
outcomes of dengue in returned Australian travellers, applying the revised WHO
dengue classification (2009) to this population. DESIGN, SETTING AND
PARTICIPANTS: Retrospective case series analysis of confirmed dengue cases
hospitalised at one of four Australian tertiary hospitals, January 2012 - May
2015. MAIN OUTCOME MEASURES: Clinical features, laboratory findings and outcomes
of patients with dengue; dengue classification according to 2009 WHO guidelines.
RESULTS: 208 hospitalised patients (median age, 32 years; range, 4-76 years) were
included in the study. Dengue was most frequently acquired in Indonesia (94
patients, 45%) and Thailand (40, 19%). The most common clinical features were
fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO
criteria for dengue with warning signs, and one the criteria for severe dengue;
the most common warning signs were mucosal bleeding (44 patients, 21%) and
abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133,
64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory
findings. 46 patients (22%) had serological evidence of previous exposure to
dengue virus. WHO guidelines were documented as a management benchmark in ten
cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs
(NSAIDs). CONCLUSIONS: A significant proportion of returning Australian
travellers hospitalised for dengue have unrecognised warning signs of severe
disease. Many received NSAIDs, which can increase the risk of haemorrhage in
dengue. As travel to Asia from Australia continues to increase, it is vital for
averting serious outcomes that clinicians can recognise and manage dengue.
PMID- 28403753
TI - Australasian Society for Infectious Diseases: low value interventions.
PMID- 28403754
TI - Is Australia prepared for the next pandemic?
PMID- 28403755
TI - Translating our microbiome into medicine.
PMID- 28403757
TI - Is it human?
PMID- 28403758
TI - Leaving my father.
PMID- 28403756
TI - First confirmed case of transfusion-transmitted hepatitis E in Australia.
PMID- 28403759
TI - Death from an untreatable infection may signal the start of the post-antibiotic
era.
PMID- 28403760
TI - Dengue and travellers: implications for doctors in Australia.
PMID- 28403761
TI - Trends in the prevalence of hepatitis B infection among women giving birth in New
South Wales.
AB - OBJECTIVES: To evaluate the effect of targeted and catch-up hepatitis B virus
(HBV) vaccination programs in New South Wales on HBV prevalence among women
giving birth for the first time. DESIGN: Observational study linking data from
the NSW Perinatal Data Collection for women giving birth during 2000-2012 with
HBV notifications in the NSW Notifiable Conditions Information Management System.
MAIN OUTCOME MEASURES: HBV prevalence in Indigenous Australian, non-Indigenous
Australian-born, and overseas-born women giving birth. RESULTS: Of 482 944 women
who gave birth to their first child, 3383 (0.70%) were linked to an HBV
notification. HBV prevalence was 1.95% (95% CI, 1.88-2.02%) among overseas-born
women, 0.79% (95% CI, 0.63-0.95%) among Indigenous Australian women, and 0.11%
(95% CI, 0.09-0.12%) among non-Indigenous Australian-born women. In Indigenous
Australian women, prevalence was significantly lower for those who had been
eligible for inclusion in the targeted at-risk newborn or universal school-based
vaccination programs (maternal year of birth, 1992-1999: 0.15%) than for those
who were not (born <= 1981: 1.31%; for trend, P < 0.001). There was no
statistically significant downward trend among non-Indigenous Australian-born or
overseas-born women. HBV prevalence was higher among Indigenous women residing in
regional and remote areas than those in major cities (adjusted odds ratio [aOR],
2.23; 95% CI, 1.40-3.57), but lower for non-Indigenous (aOR, 0.39; 95% CI, 0.28
0.55) and overseas-born women (aOR, 0.61; 95% CI, 0.49-0.77). CONCLUSION: Among
women giving birth, there was a significant reduction in HBV prevalence in
Indigenous women associated with the introduction of the HBV vaccination program
in NSW, although prevalence remains higher than among non-Indigenous Australian
born women, and it also varies by region of residence. Continuing evaluation is
needed to ensure that the prevalence of HBV infections continues to fall in
Australia.
PMID- 28403762
TI - Treatment of latent tuberculosis infections in the Darwin region.
PMID- 28403763
TI - The microbiology of crocodile attacks in Far North Queensland: implications for
empirical antimicrobial therapy.
PMID- 28403764
TI - Clinical experience of patients with hepatitis C virus infection among Australian
GP trainees.
PMID- 28403765
TI - The Australasian Society for Infectious Diseases and Refugee Health Network of
Australia recommendations for health assessment for people from refugee-like
backgrounds: an abridged outline.
AB - INTRODUCTION: In 2009, the Australasian Society of Infectious Diseases published
guidelines on the post-arrival health assessment of recently arrived refugees.
Since then, the number of refugees and asylum seekers reaching Australia has
increased substantially (17 555 refugees in 2015-16) and the countries of origin
have changed. These groups are likely to have had poor access to health care pre
arrival and, consequently, are at risk of a range of chronic and infectious
diseases. We established an advisory group that included infectious diseases
physicians, general practitioners, public health specialists, paediatricians and
refugee health nurses to update the 2009 guidelines.Main recommendations: All
people from refugee-like backgrounds, including children, should be offered a
tailored comprehensive health assessment and management plan, ideally within 1
month of arrival in Australia. This can be offered at any time if initial contact
with a GP or clinic is delayed. Recommended screening depends on history,
examination and previous investigations, and is tailored based on age, gender,
countries of origin and transit and risk profile. The full version of the
guidelines is available at http://www.asid.net.au/documents/item/1225.Changes in
management as a result of this guideline: These guidelines apply to all people
from refugee-like backgrounds, including asylum seekers. They provide more
information about non-communicable diseases and consider Asia and the Middle East
as regions of origin as well as Africa. Key changes include an emphasis on person
centred care; risk-based rather than universal screening for hepatitis C virus,
malaria, schistosomiasis and sexually transmissible infections; updated
immunisation guidelines; and new recommendations for other problems, such as
nutritional deficiencies, women's health and mental health.
PMID- 28403766
TI - Controversies in diagnosis and management of community-acquired pneumonia.
AB - Community-acquired pneumonia (CAP) is a common condition; however, it appears to
be overdiagnosed. Diagnosing CAP too frequently may be adding to the problems of
overuse of antibiotics, such as bacterial resistance in the community and greater
costs and complications in individuals. Data support that most patients with non
severe CAP can be treated for 3-5 days; however, most patients with CAP are
receiving much longer courses of therapy. Macrolides such as azithromycin have
the potential to prolong the QT interval, although large population studies show
that this does not appear to result in excess cardiac mortality. CAP is
associated with an increase in a variety of cardiac complications, most notably
infarctions and worsening cardiac failure, so clinicians should be vigilant for
signs and symptoms of these complications, particularly in patients with a
history of ischaemic cardiac disease or the presence of cardiac risk factors.
Cardiac risk factors should be assessed and managed in patients with CAP over 40
years of age, although there are yet to be data to show that this approach
reduces deaths. Corticosteroids may have a slight effect on reducing deaths in
patients with severe CAP, but this must be balanced against the significant
potential for side effects.
PMID- 28403767
TI - Tick-borne infectious diseases in Australia.
AB - Tick bites in Australia can lead to a variety of illnesses in patients. These
include infection, allergies, paralysis, autoimmune disease, post-infection
fatigue and Australian multisystem disorder. Rickettsial (Rickettsia spp.)
infections (Queensland tick typhus, Flinders Island spotted fever and Australian
spotted fever) and Q fever (Coxiella burnetii) are the only systemic bacterial
infections that are known to be transmitted by tick bites in Australia. Three
species of local ticks transmit bacterial infection following a tick bite: the
paralysis tick (Ixodes holocyclus) is endemic on the east coast of Australia and
causes Queensland tick typhus due to R. australis and Q fever due to C. burnetii;
the ornate kangaroo tick (Amblyomma triguttatum) occurs throughout much of
northern, central and western Australia and causes Q fever; and the southern
reptile tick (Bothriocroton hydrosauri) is found mainly in south-eastern
Australia and causes Flinders Island spotted fever due to R. honei. Much about
Australian ticks and the medical outcomes following tick bites remains unknown.
Further research is required to increase understanding of these areas.
PMID- 28403768
TI - Australian transplant recipients are at risk of chronic hepatitis E.
PMID- 28403769
TI - Legionnaires' disease cluster investigation in Sydney.
PMID- 28403770
TI - Adaptation of a biobank certification program for Australia.
PMID- 28403771
TI - Factors affecting general practitioner charges and Medicare bulk-billing: results
of a survey of Australians - erratum.
PMID- 28403773
TI - Progress of CDK4/6 Inhibitor Palbociclib in the Treatment of Cancer.
AB - The cyclin-dependent kinases (CDKs) and their cyclin partners are key regulators
of the cell cycle. These kinases are closely related to oncogenesis and have been
proved to be attractive targets for designing novel anticancer agents. The CDK
inhibitors can effectively suppress the excessive proliferation of tumor cells by
inducing cell cycle arrest. In recent years, a large number of CDK inhibitors
have entered pre-clinical and/or clinical trials. Among these compounds, the
selective CDK4/6 inhibitor Palbociclib has been approved by FDA for breast cancer
treatment. Moreover, Palbociclib demonstrated promising antitumor potential as
monotherapy or combined therapy in numerous clinical trials. Herein, we provide a
brief review focused on the recent progress of clinical studies about
Palbociclib.
PMID- 28403774
TI - Pharmacogenetics of Aromatase Inhibitors in Endocrine Responsive Breast Cancer:
Lessons Learnt from Tamoxifen and CYP2D6 Genotyping.
AB - BACKGROUND: Genetics play a significant role in drug metabolism of endocrine
therapy of breast cancer. These aspects have been studied extensively in patients
on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less
established. In contrast to the protective effect of tamoxifen, aromatase
inhibitors are linked with an increased risk for bone loss and fractures.
OBJECTIVE: This review outlines key issues in the implementation of
pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of
aromatase inhibitors in postmenopausal women with estrogen receptor positive
breast cancer. METHODS: Lessons learnt from the association between tamoxifen and
CYP2D6 genotyping were applied to identify polymorphisms with the potential to
change clinical decision-making in patients on aromatase inhibitors. The ability
of next generation sequencing to supersede single-gene analysis was furthermore
evaluated in a subset of breast cancer patients on aromatase inhibitors selected
from a central genomics database. RESULTS: Methodological flaws in major
randomised controlled trials and continued referral to incorrect results in
expert consensus statements are important factors delaying the implementation of
CYP2D6 pharmacogenetics in tamoxifen treatment. This highlighted the importance
of a clinical pipeline including comprehensive genotyping, to define the target
population most likely to benefit from aromatase inhibitor pharmacogenetics.
CONCLUSION: The clinical utility of CYP2D6 genotyping is well-established in
patients at increased risk of tamoxifen resistance due to cumulative risk. The
pharmacogenetics of CYP19A1 requires further clarification in terms of bone risk
assessment for appropriate use in the treatment algorithm of high-risk patients
at the onset of aromatase inhibitors.
PMID- 28403775
TI - Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2
one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors.
AB - BACKGROUND: Alkynes are fundamental building blocks in synthetic chemistry with
high pharmaceutical applications. Among the bioactive acetylenic molecules,
propargylic alcohol is most important as almost all the marketed drugs contains
quaternary centered propargylic alcohol functionality. OBJECTIVE: In this study
we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives
for in vitro cytotoxic activity. METHOD: An expeditious method for direct
alkynylation of isatins (ketones) has been developed using tetrabutylammonium
fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free
conditions. Furthermore, this method is an economically viable process that also
compliments green aspects like being a ligand/metal free process under ambient
conditions. This reaction tolerated a wide range of substrates with good to
excellent yields (80-94%). RESULTS: The results showed that the synthesized
compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with
IC50 values ranging from 7.7 to 9.8 uM. CONCLUSION: All the 3-hydroxy-3
ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity
on five different cancer cell lines. Further, the synthesized compounds (4m, 4n
and 4p) were evaluated for their ability to inhibit Akt kinase activity and
exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 uM..
PMID- 28403776
TI - Eco-friendly Synthesis of Pyrido[2,3-d]pyrimidine Analogs and Their Anticancer
and Tyrosine Kinase Inhibition Activities.
AB - BACKGROUND: One of the promising scaffolds in drug discovery is the fused
pyrimidine derivatives. OBJECTIVE AND METHOD: Efficient synthesis of a novel
series of 18 new 1,8-naphthyridine-3-carbonitrile, 2-amino pyrido[2,3
d]pyrimidine derivatives via multi-component reactions of aromatic aldehydes,
active methylene, and an aromatic amine under microwave irradiation and
evaluation of their anticancer activity and possible mechanisms. RESULTS: Only
compounds 5 (a-c) had a significant antiproliferative activity in hepatic HepG2
cells at submicromolar concentration (7.5-10 uM). Similarly, only compound 11 (a
c) had a significant activity in breast MCF7 cells at (4-7 uM). Derivatives with
one methoxyphenyl substitution (5a and 11a) were not different from derivatives
having dimethoxyphenyl substitution (5b and 11b). However, thiophene substitution
(5c and 11c) enhanced the anticancer activity in both cells lines examined by 25%
in HepG2 and by ~45% in MCF7 cells compared to a and b derivatives. All compounds
were safe to both normal human lung cells (WI-38) and RBCs at concentrations up
to 40 mM. The antiproliferative activity of compounds 5 (a-c) in HepG2 could be
attributed to an induction of intrinsic apoptotic pathway as evidenced from the
induction of initiator caspase 9 by ~ 4 folds. While, the activity of compounds
11 (a-c) could be attributed to their potential to inhibit tyrosine kinases (TK)
by up to 85%. The IC50 of derivative 11c against TK was at 173 nM. CONCLUSION:
The present study reported that derivatives 5 and 11 have merit for further
investigation as anticancer and TK inhibitors.
PMID- 28403777
TI - Potential Molecular Targets of Ampelopsin in Prevention and Treatment of Cancers.
AB - Cancers have increased threat to human health due to the limited treatment
efficacy of chemotherapy and radiotherapy with a series of toxicity and side
effects; therefore, the development and utilization of natural products with
potential preventive and therapeutic efficacy, and less toxicity and side effects
will be beneficial to promote the health of cancer patients. In this article, the
activity of ampelopsin as a natural flavonoid and its underlying molecular
mechanisms for the prevention and treatments of hepatic carcinoma, breast cancer,
prostate cancer and melanoma through inhibiting cell proliferation, accelerating
apoptosis, inducing reactive oxygen species (ROS) generation and endoplasmic
reticulum (ER) stress, suppressing angiogenesis, invasion and metastasis, and
synergizing the efficacy of other anti-cancer drugs have been summarized. This
study will provide a reference for the development and utilization of other
natural products.
PMID- 28403778
TI - Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of
Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.
AB - BACKGROUND: Myc (c-Myc) alone activates the embryonic stem cell-like
transcriptional module in both normal and transformed cells. Its dysregulation
might lead to increased cancer stem cells (CSCs) population in some tumor cells.
OBJECTIVE: In order to investigate the potential of Myc decoy
oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells
(mESCs) were used in this study as a model of CSCs. To our best of knowledge this
is the first report outlining the application of Myc decoy in transcription
factor decoy "TFD" strategy for inducing differentiation in mESCs. METHODS: A 20
mer double-stranded Myc transcription factor decoy and scrambled
oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility
shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i)
condition. Further investigations were carried out using fluorescence and
confocal microscopy, cell proliferation and apoptosis analysis, alkaline
phosphatase and embryoid body formation assay, real-time PCR and western
blotting. RESULTS: EMSA data showed that Myc decoy ODNs bound specifically to c
Myc protein. They were found to be localized in both cytoplasm and nucleus of
mESCs. Our results revealed the potential capability of Myc decoy ODNs to
decrease cell viability by (16.1+/-2%), to increase the number of cells arrested
in G0/G1 phases and apoptosis by (14.2+/-3.1%) and (12.1+/-3.2%), respectively
regarding the controls. Myc decoy could also modulate differentiation in mESCs
despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our
medium. CONCLUSION: The optimized Myc decoy ODNs approach might be considered as
a promising alternative strategy for differentiation therapy investigations.
PMID- 28403779
TI - Design, Synthesis and Biological Evaluation of Betulinic Acid Derivatives as New
Antitumor Agents for Leukemia.
AB - BACKGROUND: Chronic myeloid leukemia (CML) is currently treated with imatinib, a
Bcr-Abl inhibitor. However, resistance to this drug usually develops over time.
Triptolide, a diterpenoid triepoxide, has been shown active against CML cells
resistant to imatinib, acting mainly on the level of Bcr-Abl transcription
inhibition. OBJECTIVE: Here, we used the triterpene betulinic acid, a known
proteasome inhibitor with potential antileukemic activity, as a scaffold for the
generation of analogues with predicted triptolide biological activity. METHOD:
Betulinic acid derivatives were designed based on the structure-activity
relationship of triptolide and evaluated for their cytotoxic effects in CML
cells, lymphocytes and human keratinocytes (HaCaT), as well as against the
proteasome complex. The main modification performed on betulinic acid was
fluorination at C-28 and epoxidation, both of which are responsible for enhancing
activity of triptolide. A total of 10 compounds were obtained: 6 previously
described and 4 novel compounds. The cytotoxic activity over a CML cell line
(K562) was assessed using flow cytometry and compared to lymphocytes and HaCaT.
RESULT: The results show that betulinic acid was the most cytotoxic compound
against CML cells, showing a good selectivity index for cancer over normal cells.
The most important trend for the activity in betulinic acid derivatives is the
presence of a free hydroxyl group at C-3 and a carboxyl group at C-28. Results
also indicated that the epoxide is important for enhancing the activity, while
modification at C-28 worsens the activity. CONCLUSION: Proteasome inhibition
assays suggest that proteasome is the main target for betulinic acid and its
derivatives.
PMID- 28403780
TI - Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological
Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents.
AB - OBJECTIVE AND METHOD: A new series of benzothiazole-piperazine derivatives was
synthesized and a complete chemical characterization of the novel compounds was
provided. In vitro cytotoxic activities were screened against colorectal (HCT
116), breast (MCF-7) and hepatocellular (Huh7) cancer cell lines by
Sulforhodamine B assay. RESULT AND DISCUSSION: All compounds showed cytotoxic
activity against hepatocellular (Huh7) and breast (MCF-7) cancer cell lines.
Dihalo substituted benzylpiperazine derivatives (2a, 2e) had the highest
cytotoxic activities in all the tested cell lines. In addition,
acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory
activities of synthesized compounds were investigated by in vitro Ellman's
method. Compound 2j led to moderate and selective inhibition against AChE.
Docking study was utilized to understand the binding mode of compound 2j in
comparision with donepezil on AChE. The other tested compounds showed weak or no
inhibition against AChE as promising anticancer agents.
PMID- 28403781
TI - Design, Synthesis and Biological Evaluation of Novel 1, 3- thiazolidine-2, 4
diones as Anti-prostate Cancer Agents.
AB - BACKGROUND: Androgen receptor is an attractive target for the treatment of
prostate cancer. The 1,3- thiazolidine-2,4-diones possess a wide diversity of
important biochemical effects and interesting pharmacological properties.
OBJECTIVE: The aim of the study is to find the experimental and computational
methods to investigate the interference of 1,3-thiazolidine-2,4-diones with
androgen receptor against prostate cancer. METHOD: Structural modification and
molecular docking-based virtual screening approaches were imposed to identify the
novel 1,3-thiazolidine-2,4-diones by using Schrodinger (Maestro 9.5). The best
fit molecules (3-12 & 23-31) were synthesized and characterized using
spectroscopic techniques, then in vitro antioxidant and antiprostate cancer
activities were evaluated. Further, the structure of the intermediate (18) was
confirmed by single crystal XRD analysis. The mechanism studies were performed
through the gene expression for the compounds, 29, 30, and 31, the standards,
dihydrotestosterone and R-bicalutamide. RESULTS: The compounds, 29, 30 and 31
showed comparatively significant antioxidant activity and better
antiproliferative activity against PC-3 and LNCaP cell lines. Also, very low
cytotoxicity was observed in the noncancerous cell (3T3). The compounds, 29, 30
and 31 significantly decreased the mRNA expression of ARstimulated genes, PSA and
TMPRSS2, which demonstrated their anti-prostate cancer activities. ADME/T
properties prediction of the compounds (3-12 and23-31) showed the promising drug
likeness and pharmacokinetic parameters without toxicity. Moreover, DFT
calculations apparently confirmed the stable conformer of the compound, 31.
CONCLUSION: These findings may provide the essential information for the
development of anti-prostate cancer agents.
PMID- 28403782
TI - Synthesis, Cytotoxicity and Antimicrobial Activity of New Enmein-type Kauranoid
Diterpenoid Derivatives.
AB - BACKGROUND: Recently, we devoted to disclosing the antibacterial activities of
enmein-type 6,7-seco-ent-kauranoid derivatives. OBJECTIVE: Eleven new enmein-type
diterpenoid derivatives with different substituents and drug-like properties were
designed and synthesized. METHOD: The antimicrobial activities against E. coli,
S. aureus, B. subtilis and M. albicans were disclosed. The antiproliferative
activities against human cancer Bel-7402, K562, MGC-803 and CaEs-17 cells and non
cancerous L-02 cells were also measured by MTT method. RESULTS: The results
revealed that enmein-type diterpenoids showed more promising activities against
tested gram-positive bacteria than gram-negative bacterium and fungus. Compound 9
with R of 2-quinolyl group exhibited the strongest antimicrobial activities with
MIC values of 7.81 ug/ml and 0.98 ug/ml against S. aureus and B. subtilis,
respectively. All the target derivatives exhibited superior cytotoxic activities
to compounds 1 and 2 against tumor cells, and slight selectivity between
cancerous cells and normal liver cells. Compound 12 with R of 3-(2-chloropyridyl)
group and IC50 values of 0.7 uM, 0.9 uM, 0.8 uM and 2.0 uM agaist four tumor
cells, respectively, was selected for further mechanism study in Bel-7402 cell
line. CONCLUSION: Compound 12 could induce S phase cell cycle arrest and
apoptosis at low concentrations via mitochondria-related pathways. The effects of
compound 12 on some apoptosis related proteins showed that CDK2 was up regulated
and ATM and cyclin A1 were down-regulated which confirmed the apoptosis and cell
cycle effects.
PMID- 28403783
TI - Synthesis and Evaluation of 2-Naphthaleno trans-Stilbenes and Cyanostilbenes as
Anticancer Agents.
AB - BACKGROUND: Naphthalene is a good structural replacement for the isovanillin
moiety (i.e. the 3- hydroxy-4-methoxyphenyl unit) in the combretastatin A-4
molecule, a natural product structurally related to resveratrol, which
consistently led to the generation of highly cytotoxic naphthalene analogues when
combined with a 3,4,5-trimethoxyphenyl or related aromatic system. Also, the
naphthalene ring system is present in many current drug molecules that are
utilized for anti-tumor, anti-arrhythmia and antioxidant therapy. OBJECTIVE: In
our continuing quest to improve the potencies of naturally occurring anti-cancer
molecules through chemical modification, we have now synthesized a small library
of 2-naphthaleno trans- stilbenes and cyanostilbenes that are structurally
related to both resveratrol and DMU-212, and have evaluated these novel analogs
against a panel of 54 human tumor cell lines. METHOD: A series of 2-naphthaleno
containing trans-stilbenes 3a-3h (Scheme 1) were synthesized by Wittig reaction
of a variety of aromatic substituted benzyl-triphenylphosphonium bromide
reactants with 2- naphthaldehyde using n-BuLi as a base in THF. A second series
of 2-naphthaleno trans-cyanostilbenes analogs 5a-5h was synthesized by reaction
of 2-naphthaldehyde (2; 1 mmol) with an appropriately substituted 2-
phenylacrylonitrile 4a-4h; 1 mmol) in 5% sodium methoxide/methanol. The reaction
mixture was stirred at room temperature for 2-3 hours and the reaction allowed to
go to completion (TLC monitoring), during which time the desired product
precipitated out of the solution as a solid. The resulting precipitate was
filtered off, washed with water and dried to yield the desired compound in yields
ranging from 70-95% (Scheme 2). RESULTS: The percentage growth inhibition of 54
human cancer cell lines in a primary NCI screen after exposure to compounds 3a,
3d, 5b and 5c was carried out. The results showed that only compounds 5b and 5c
met the criteria for subsequent testing to determine growth inhibition values
(GI50) in dose-response studies. At 10-5 M concentration, compounds 5b and 5c
exhibited cytotoxic activity against leukemia cell lines HL-60(TB) and SR, lung
cancer cell line NCI-H522, colon cancer cell lines COLO 205 and HCT-116, CNS
cancer cell line SF-539, melanoma cell line MDA-MB-435, and breast cancer cell
line BT-549. The naphthalene trans-stilbene analogue 3a, exhibited significant
growth inhibition against only one cell line, melanoma cell line MDA-MB-435 (96 %
growth inhibition). Compound 3d was inactive in the 10-5 M single dose screen.
CONCLUSION: We have synthesized a small set of novel 2-naphthaleno stilbenes and
cyanostilbenes and evaluated several of these compounds for their anticancer
properties against a panel of 54 human tumor cell lines. The most active analogs,
5b and 5c, showed significantly improved growth inhibition against the human
cancer cells in the NCI panel when compared to DMU-212. Of these compounds,
analog 5c was found to be the most potent anticancer agent and exhibited
significant growth inhibitory effects against COLO 205, CNS SF 539 and melanoma
SK-MEL 5 and MDA-MB-435 cell lines with GI50 values <= 25 nM. Analog 5b also
exhibited GI50 values in the range 25-41 nM against CNS SF 295 and melanoma MDA
MB-435 and UACC-62 cell lines. Compounds 5b and 5c were also cytotoxic towards
the MV4-11 leukemia cell line with LD50 value of 450 nM and 200 nM, respectively,
and demonstrated >50% inhibition of tubulin polymerization at concentrations
below their LD50 values in these cells. In silico docking studies suggest that
compounds 5b and 5c bind favorably at the colchicine- binding pocket of the
tubulin dimer, indicating that both 5b and 5c may inhibit tubulin polymerization
through a mechanism similar to that exhibited by colchicine. Derivative 5c
demonstrated more favorable binding based on the docking score and buried surface
area, as compared to compound 5b, in agreement with the higher observed potency
of 5c against a broader range of tumor cell lines. Based on these results, analog
5c is considered to be a lead compound for further optimization as a clinical
candidate for treating a variety of cancers.
PMID- 28403784
TI - Synthesis, Characterization of 4-Anilino-6,7-Dimethoxy Quinazoline Derivatives as
Potential Anti-Angiogenic Agents.
AB - BACKGROUND: Quinazolines are a big family of heterocyclic compounds with anti
cancer properties. OBJECTIVE: The latest investigation was on synthesis,
characterization of novel 4-anilinoquinazoline derivatives for their anti
angiogenic effect. METHOD: A series of novel 4-anilino-6,7-dimethoxy quinazoline
derivatives were synthesized and characterized using 1H, 13C NMR, FT-IR and LC-MS
techniques. Cytotoxicity assays were performed for all compounds against
different cell lines such as Human colon carcinoma (HCT116), Human chronic
myeloid leukemia (K562) and Human breast cancer (SKBR3) cell lines using 3-(4,5
Dimethylthiazol-2-yl)-2,5-Diphenyl tetrazolium Bromide (MTT), Trypan blue and
Lactose dehydrogenase release assay. The selected compounds were evaluated for
their anti-tumor and anti-angiogenic effect on EAC tumor model. The molecular
docking studies were drawn using maestro 2D sketcher and energy minimize was
compounded by OPLS 2005. RESULTS: Among all compounds, RB4 and RB7 showed
moderate activity whereas RB1 showed most potent activity comparable with that of
the standard drug cisplatin against all three cell lines. RB1 also inhibited the
proliferation of tumor cells in three different cell lines. Further, in-vivo
studies revealed that RB1 significantly reduced secretion of ascites, tumor cell
proliferation and increased the life span of tumor bearing mice. The
antiangiogenic effect of RB1 was revealed from the reduced vessel sprouting in
the peritoneum region of treated mice and induced avascular zone in
chorioallantoic membrane (CAM) model. The insilco molecular docking studies
clearly demonstrate the dual inhibitory potential of RB1 against VEGFR-2 and EGFR
from binding to the active site of its receptors. CONCLUSION: However these
studies clearly show that RB1 might be a potent antitumor and anti-angiogenic
agent representing a promising lead for further optimization and elucidation of
the mechanism of action.
PMID- 28403785
TI - Apoptotic Effects of Some Tetrahydronaphthalene Derivatives on K562 Human Chronic
Myelogenous Leukemia Cell Line.
AB - BACKGROUND: Retinoids which are vitamin A (Retinol) derivatives have been
suggested to mediate the inhibition of cancer cell growth and apoptosis. It has
been reported that all trans retinoic acid (ATRA) exhibited suppressive effects
on different types of leukemia including chronic myelogenous leukemia. OBJECTIVE:
In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8
pentamethyl-5,6,7,8- tetrahydronaphthalene-2-yl)-carboxamide derivatives
(compound 6-12) on cell viability and apoptotic pathways in K562 human chronic
myelogenous leukemia cell line. METHODS: Cell viability and apoptosis were
examined by spectrophotometric thiazolyl blue tetrazolium bromide (MTT) and
caspase-3 assay, western blot, RT-PCR and flow cytometry. RESULTS: Our results
indicated that compound 6 (5-(1,2-Dithiolan-3-yl)-N-(3,5,5,8,8-pentamethyl
5,6,7,8- tetrahydronaphthalen-2-yl)pentanamide), 8 (4-(3,4-Dimethoxyphenyl)-N
(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)butanamide) and 11 (E-3
(4-Hydroxy-3-methoxyphenyl)-N-(3,5,5,8,8-pentamethyl- 5,6,7,8
tetrahydronaphthalen-2-yl)acrylamide) exhibited apoptotic effects in K562 human
chronic myelogenous leukemia cell line and induced caspase 3, PARP cleavage,
Bax/Bcl-2 ratio, Bad and Bim gene expressions. CONCLUSION: Some retinoid
derivatives tested in this study induced apoptosis of K562 cells which suggest
that these compounds may serve as potential agents in the treatment of chronic
myelogenous leukemia.
PMID- 28403786
TI - Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue.
AB - Although survival of patients with different types of cancer has improved,
cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac
dysfunction after treatment with anthracyclines has historically been a major
problem. However, also targeted therapies and biological molecules can induce
reversible and irreversible cardiac dysfunction. Over the last years, cancer
immunotherapies haverevolutionized the clinical management of a wide spectrum of
solid and hematopoietic malignancies previously endowed with poor prognosis.
Immune checkpoint inhibitors are at the forefront of immunotherapy: the two most
prominent are the targeting of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-
4) and of programmed cell death 1 (PD-1) and its ligand PD-L1. Ipilimumab (anti
CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking
monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1
(atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed.
Inhibitors of CTLA-4 and PD-1/PD-L1 pathway can unleash anti-tumor immunity and
mediate cancer regressions. Although CTLA-4 inhibitors and PD-1 and PD-L1
blocking agents are frequently associated with a wide spectrum of immune-related
adverse events, cardiac toxicity has been underestimated. However, early animal
studies have demonstrated that after CTLA-4 inhibition and PD-1 deletion
autoimmune myocarditis can occur. Moreover, PD-1 and PD-L1 can be expressed in
rodent and human cardiomyocytes. During the last years several cases of fatal
heart failure have been documented in melanoma patients treated with checkpoint
inhibitors. The recent experience with cardiovascular toxic effects associated
with checkpoint inhibitors introduces important concepts biologically and
clinically relevant for future oncology trials and clinical practice.
PMID- 28403787
TI - Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis
in the Pathogenesis of Diabetic Retinopathy.
AB - Diabetic retinopathy (DR) is a major diabetes complication and the leading cause
for vision loss and blindness in the adult human population. Diabetes, being an
endocrinological disorder dysregulates a number of hormonal systems including the
renin angiotensin system (RAS), which thereby may damage both vascular and
neuronal cells in the retina. Angiotensin II (Ang II), an active component of the
RAS is increased in diabetic retina, and may play a significant role in
neurovascular damage leading to the progression of DR. In this review article, we
highlight the role of Ang II in the pathogenesis of retinal damage in diabetes
and discuss a newly identified mechanism involving tissue chymase and angiotensin
(1-12) [Ang-(1-12)] pathways. We also discuss the therapeutic effects of
potential RAS inhibitors targeting blockade of cellular Ang II formation to
prevent/ protect the retinal damage. Thus, a better understanding of Ang II
formation pathways in the diabetic retina will elucidate early molecular
mechanism of vision loss. These concepts may provide a novel strategy for
preventing and/or treating diabetic retinopathy, a leading cause of blindness
worldwide.
PMID- 28403789
TI - Metaflammation: Tissue-Specific Alterations of the NLRP3 Inflammasome Platform in
Metabolic Syndrome.
AB - In the last decades, the extension of life expectancy and the increased
consumption of foods rich in saturated fats and added sugars have exposed the
general population to emerging health problems. The prevalence of metabolic
syndrome (MS), composed of a cluster of factors as obesity, dyslipidemia,
hyperglycemia, and hypertension, is rapidly increasing in industrialized and
developing countries leading to precocious onset of age-related diseases. Indeed,
oxidative stress, accumulation of advanced glycation endproducts, and a chronic
low-grade inflammation are common features of MS and physiological ageing. In
particular, the entire set of MS factors contributes to the development of an
inflammatory status named metaflammation, which has been associated with
activation of early innate immune response through the assembling of the
multiprotein complex inflammasome. The most investigated family of inflammasome
platforms is the NOD-like receptor pyridine containing (NLRP) 3, which is
activated by several exogenous and endogenous stimuli, leading to the sequential
cleavage of caspase-1 and IL-1beta, followed by secretion of active IL-1beta. We
here collect the most recent findings on NLRP3 activation in MS providing
evidence of its central role in disease progression and organ dysfunction in
target tissues of metaflammation, in particular in cardiovascular, hepatic and
renal complications, with a focus on oxidative stress and advanced glycation
endproducts. A wide overview of the most promising strategies for the modulation
of NLRP3 activation and related metabolic repercussions is also provided, since
the finding of specific pharmacological tools is an urgent requirement to reduce
the social and economic burden of MS- and elderly-associated diseases.
PMID- 28403788
TI - Effect of Metformin and Statin Use on Survival in Pancreatic Cancer Patients: a
Systematic Literature Review and Meta-analysis.
AB - BACKGROUND AND OBJECTIVE: Current epidemiological studies report conflicting
results for the effect of statin or metformin on pancreatic cancer overall
survival. This literature review and meta-analysis summarize the studies
reporting an association between statin or metformin use and overall survival of
pancreatic cancer patients. METHODS: We systematically searched for studies about
the association between statin or metformin use and pancreatic cancer overall
survival in electronic databases (PubMed, ISI Web of Science, MEDLINE, Cochrane,
Scopus, Google Scholar). A meta-analysis based on hazard ratios (HRs) and 95%
confidence intervals (CIs) was performed using random effect models.
Heterogeneity between the studies was examined using I2 statistics, and
sensitivity analyses were conducted to assess the robustness of the findings.
RESULTS: Of 116 statin-related articles identified, 6 retrospective cohort
studies representing 12,057 patients were included. There was significant
heterogeneity between studies. Statin use was associated with improved survival
among pancreatic cancer patients (meta-HR = 0.75; 95% CI: 0.59, 0.90; P < 0.001).
Of 311 metformin-related articles, 8 retrospective cohort studies and 2
randomized clinical trials, representing 3,042 patients were identified.
Metformin use was associated with better overall survival among pancreatic cancer
patients (meta-HR = 0.79; 95% CI: 0.70, 0.92, P < 0.001), and significant
heterogeneity was observed between studies. CONCLUSION: Our findings suggest that
the improved survival time of pancreatic cancer patients are associated with
statin or metformin use. Due to the multiple sources of heterogeneity of the
original studies, these findings should be considered cautiously, and confirmed
with larger prospective individual-level studies.
PMID- 28403790
TI - Molecular Design and Medicinal Applications of Nano-Nitric Oxide Delivery
Systems.
AB - BACKGROUND: Nitric oxide (NO) plays important regulatory roles in a plethora of
biological functions and thus holds tremendous potential to be exploited for
clinical uses. However, the chemistries in the molecular design of nano-nitric
oxide delivery systems is currently lacking. OBJECTIVE: The overarching aim of
this review is to provide the readers with the fundamentals that relate to the
design of NO release molecules (NORMs), loading and releasing mechanism, as well
as delivery of NORMs for nanotherapeutics. METHODS: We conducted a thorough
literature search on the design and synthesis of NORMs, as well as the current
state-of-the-art NO compatible delivery platforms to address various clinical
needs. RESULTS: N-diazeniumdiolate and S-nitrosothiol based NO molecules are
among the most widely used NORMs for anti-cancer and anti-microbial applications.
The innovative integration of these NORMs with cytocompatible organic and
inorganic nanocarriers enabled controlled spatiotemporal delivery and release of
NO at the targeted diseased sites. CONCLUSION: We have provided a comprehensive
summary of the fundamental chemistries underpinning the molecular design of the
NORMs and critically assessed the recent advancements of nano-NO delivery systems
for advanced biomedical applications.
PMID- 28403791
TI - Multimeric System of RGD-Grafted PMMA-Nanoparticles as a Targeted Drug- Delivery
System for Paclitaxel.
AB - BACKGROUND: Polymer-based nanoparticles as drug-delivery systems offer new
therapeutic opportunities. Among them, ligand-mediated targeting, which increases
selectivity and efficacy, allows controllable drug delivery. The aim of the this
research was to prepare and characterize poly(methyl methacrylate) (PMMA)
nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide
sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed
at the sites of integrin receptor overexpression. METHODS: Nanoparticles were
characterized by FT-IR and Raman spectroscopy, dynamic light scattering, zeta
potential and transmission electron microscopy. RESULTS: RGD-PMMA-PTX size
distribution was 17.58 +/- 7.45 nm with a zeta potential of -38.73 +/- 5.62 mV.
According to the boxLucas Model, PTX was incorporated into nanoparticles with an
entrapment efficiency of 100% (evaluated by HPLC analysis). In vitro sustained
release was determined, with the maximum release of 55% and 40% after 21 days at
pH 5.3 and 7.4, respectively. The highest inhibition on cell proliferation was
found with RGD-PMMA-PTX nanoparticles (90 %). CONCLUSION: The obtained results
showed that RGD-PMMA-PTX represents an attractive and suitable therapeutic
approach for targeting overexpressed integrins in the cancer cells.
PMID- 28403792
TI - Nanocarriers in Improving Chemotherapy of Multidrug Resistant Tumors: Key
Developments and Perspectives.
AB - The multidrug resistance (MDR) of tumor cells significantly reduces the
efficiency of traditional anticancer therapy. Tumor MDR is complex and involves
several mechanisms such as decreased drug uptake, increased drug efflux, enhanced
drug exocytosis, increased drug detoxification and inactivation by
drugmetabolizing enzymes, altered drug targets due to genetic and epigenetic
modifications, altered DNA repair, and impaired apoptotic pathways.
Implementation of nanoparticles can markedly improve drug delivery through
increased stability in the plasma, prolonged half-life, enhanced specificity of
transfer, and advanced drug accumulation and retention in the tumor cells. So
far, many various types of nanocarriers have been used for the delivery of
anticancer agents. These carriers greatly increase anti-tumor effects of
cytotoxic agents since drug-carrying nanoparticles are able to reverse MDR. The
promising integrative approach in cancer nanotherapy assumes the development of
multifunctional delivery systems simultaneously transmitting various agents such
as drugs, genes, imaging agents, and targeting ligands in order to enhance anti
tumor toxicity and nanoparticle tracking.
PMID- 28403793
TI - More than Just Size: Challenges and Opportunities of Hybrid Dendritic
Nanocarriers.
AB - BACKGROUND: Dendrimers and hyperbranched polymers are emerging polymer
architectures that attract increasing attention due to their unique topological
structure and interesting physicochemical properties. Their enormous potential
makes them particularly attractive to form new and fascinating nanometric drug
delivery systems, solving several typical shortcomings encountered in
nanomedicine. OBJECTIVE: In this context, the recent developments of dendritic
and hyperbranched based systems, together with their application as nanocarriers,
have been comprehensively reviewed. CONCLUSION: This review highlights how the
structural complexity can be taken as an evolution parameter of these
nanosystems, starting with hyperbranched polymers and evolving to more complex
structures such as hybrid dendritic- inorganic nanoparticles and dendronized nano
objects hierarchically designed. Finally, future directions and perspectives in
this promising field are briefly discussed.
PMID- 28403794
TI - Ultrasound Assisted Synthesis of Quinoline Derivatives in the Presence of
SnCl2.2H2O as a Precatalyst in Water: Evaluation of their Antibacterial
Activities.
AB - BACKGROUND: SnCl2.2H2O has been used as a convenient precatalyst for the one-pot
and rapid synthesis of 2-substituted quinolines under ultrasound irradiation in
water. The reaction involved a 3-component reaction of aniline, aldehydes, and
ethyl 3,3-diethoxypropionate in the presence of aerial oxygen to give the desired
products in good yields. CONCLUSION: Several of these compounds showed
antibacterial activities when tested against gram-positive and gram-negative
species. One compound i.e. 4b showed promising activities across both the
species.
PMID- 28403796
TI - Riboswitches as Potential Targets for the Development of Anti-Biofilm Drugs.
AB - In nature, bacteria can exist as single motile cells or as sessile cellular
community, known as microbial biofilms. Bacteria within biofilms are embedded in
a self-produced extracellular matrix that makes them more resistant to antibiotic
treatment and responses of the host immune system. Microbial biofilms are very
important in medicine since they are associated with several human diseases such
as dental caries, periodontitis, otitis media, infective endocarditis, infectious
kidney stones, osteomyelitis or prostatitis. In addition, biofilms formed on the
surface of clinical devices such as pacemakers, implants and catheters are
difficult to treat, which underlines the clinical relevance of biofilm formation.
At the molecular level, the switch from the planktonic state to biofilm formation
is regulated primarily by bis- (3'-5)-cyclic dimeric guanosine monophosphate (c
di-GMP). C-di-GMP performs its function by binding to a wide variety of proteins,
but also to riboswitches. C-di-GMP riboswitches are RNA regulatory elements
located in the 5'-untranslated regions (5'-UTRs) of RNA messengers (mRNA) from
genes involved in virulence, motility and biofilm formation, which are regulated
by changes in the intracellular concentration of c-di-GMP. This review discusses
the role of c-di-GMP responsive riboswitches as potential targets for the design
of anti-biofilm agents.
PMID- 28403795
TI - Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair.
AB - INTRODUCTION: Transplantation of autologous mesenchymal stem cells (MSCs) has
been shown to attenuate renal injury and dysfunction in several animal models,
and its efficacy is currently being tested in clinical trials for patients with
renal disease. Accumulating evidence indicates that MSCs release extracellular
vesicles (EVs) that deliver genes, microRNAs and proteins to recipient cells,
acting as mediators of MSC paracrine actions. In this context, it is critical to
characterize the MSC-derived EV cargo to elucidate their potential contribution
to renal repair. In recent years, researchers have performed high-throughput
sequencing and proteomic analysis to detect and identify genes, microRNAs, and
proteins enriched in MSC-derived EVs. CONCLUSION: The present review summarizes
the current knowledge of the MSC-derived EV secretome to shed light into the
mechanisms mediating MSC renal repair, and discusses preclinical and clinical
studies testing the efficacy of MSC-derived EVs for treating renal disease.
PMID- 28403797
TI - Is the Treatment with Biological or Non-biological DMARDS a Modifier of
Periodontal Condition in Patients with Rheumatoid Arthritis?
AB - BACKGROUND AND OBJECTIVE: Experimental models suggest the use of different
therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal
condition. This study evaluated the effects of conventional drug treatment and
anti-TNF therapy in patients with RA on microbiological and periodontal
condition, establishing the association of markers of periodontal infection with
indexes of rheumatic activity. MATERIALS AND METHODS: One hundred seventy nine
individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs).
The periodontal evaluation included plaque and gingival indexes, bleeding on
probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival
plaque samples for microbiological analysis. Rheumatologic evaluations included a
clinical examination, rheumatoid factor (RF), antibodies against cyclic
citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive
C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). RESULTS: Anti
TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T.
denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher
extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was
associated with a lower extension of CAL (p=0.05). The use of corticosteroids
exerted a protective effect on the number of teeth (p=0.027). The type of DMARD
affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs
titers were associated with the presence of red complex periodontal pathogens
(p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05),
and ESR was associated with a greater PD (p=0.044) and presence of red complex
(p=0.030). CONCLUSION: Different pharmacological treatments for RA affect the
clinical condition and subgingival microbiota.
PMID- 28403798
TI - Treating Older HIV-1-infected Subjects With Cobicistat-boosted Darunavir in a 48
week Phase 3 Trial.
AB - BACKGROUND: An aging HIV-1-infected population warrants examination of the
acceptability of individual antiretroviral regimens. In a previous study of
ritonavir-boosted darunavir (ARTEMIS), similar safety/efficacy profiles were
observed in younger (<=45 years) and older (>45 years) HIV-1-infected subjects.
OBJECTIVE: To evaluate safety and efficacy outcomes in HIV-1-infected younger
versus older subjects treated with cobicistat-boosted darunavir. METHOD: In a 48
week, phase 3b, open-label trial, HIV-1-infected adults were administered
darunavir 800 mg and cobicistat 150 mg once-daily with 2 nucleos(t)ide reverse
transcriptase inhibitors (N[t]RTIs). Post hoc analyses examined safety and
efficacy outcomes in subjects <=45 and >45 years. RESULTS: Of 313 subjects, 76%
were <=45 years (median [range] age, 31 [18-45]) and 24% were >45 years (49 [46
72]). Baseline median (range) viral loads were 4.75 (2.6-6.8) and 4.83 (2.7-7.0)
log10 copies/mL, and CD4+ counts were 379.0 (5-1473) and 310.5 (6-757) cells/mm3
in younger and older subjects, respectively. Through Week 48, similar proportions
of younger and older subjects had >=1 adverse event (AE; 93% vs 88%), >=1 grade 2
4 AE possibly related to study drug (13% vs 15%), and discontinued study due to
AE (3% vs 3%). At Week 48, 82% of younger and 78% of older subjects had viral
load <50 copies/mL (95% CI of the difference: -7.4% to 13.8%). A higher
proportion of older versus younger subjects took >4 concomitant medications
during the study (69% vs 57%). CONCLUSION: Safety and efficacy profiles of
cobicistat-boosted darunavir with 2 N(t)RTIs were similar in HIV-1-infected
subjects <=45 and >45 years.
PMID- 28403799
TI - Descriptive Analysis of Mortality Predictors in H1n1 Influenza in South Indian
Patients.
AB - BACKGROUND: H1N1 (hemagglutinin-H-neuroaminidase-N) influenza infection is
associated with high morbidity and mortality because of associated complications
and related factors. Predictors of mortality in H1N1 patients are studied with
very few without seasonal/pandemic declaration. This study was carried out to
describe the clinical features, complications and different risk factors that
affect the outcome in the patients with confirmed H1N1influenza infection.
METHODS: A retrospective study was done in Kasturba Medical College Hospital,
Manipal, India by analyzing the medical records of 141 patients admitted from
January, 2011 to June, 2015. RESULTS: Of the 141 patients in the study, 51.1% of
the patients were female with a mean age of 32+/-16.2 years. Fever with headache
was observed in 92.9% patients while cough in 78.7% patients and breathlessness
in 54.6% patients. On the basis of disease severity, 53.2% of the patients were
put on mechanical ventilation. For all the patients, treatment for influenza
management began with oseltemivir. Diuretics, antianxiety and corticosteroids
were given as supportive and symptomatic care which contributed to high mortality
in hospitalized patients. Mean hospitalization period was 8.5 days. During the
hospitalization, patients developed different complications i.e. 31.20% patients
developed respiratory tract infections, while 17.7% patients developed ARDS and
14.4% patients developed sepsis. The mortality rate of this study population was
found to be 29.1 %. CONCLUSION: It was observed that low oxygen saturation during
admission, high blood urea level, use of diuretics, corticosteroids, anti-anxiety
drugs and complications like ARDS, sepsis influence the mortality rate of
patients with H1N1 infection.
PMID- 28403800
TI - Elevated C-reactive Protein Levels in Women with Bipolar Disorder may be
Explained by a History of Childhood Trauma, Especially Sexual Abuse, Body Mass
Index and Age.
AB - OBJECTIVE AND BACKGROUND: To evaluate whether increased levels of high
sensitivity C- reactive protein (hs-CRP) observed in individuals with bipolar
disorder (BD) compared to healthy controls (HCs) could be influenced by a
previous exposure to early life stress (ELS) independently from other explanatory
or background variables, including age, body mass index (BMI), and the presence
of cooccurring mental disorders. METHOD: In this case-control study, we included
142 healthy controls and 92 bipolar I and II patients. The Childhood Trauma
Questionnaire was administered in a subset of 30 female patients with BD and 31
female HCs, and plasma hs-CRP was measured in all subjects. Multivariable models
adjusted the data for the possible confounding variables. RESULTS: Serum hs-CRP
levels were significantly higher in patients with BD compared to HCs. However,
after controlling for BMI, these differences were no longer significant. Around
55% of the variance in hs-CRP was explained by cumulative and independent effects
of age, BMI and childhood trauma, especially sexual abuse. CONCLUSION: Our
results show that increased hs-CRP levels in BD patients are more related to
childhood trauma, especially sexual abuse, age and BMI than to a diagnosis of BD
per se. These data suggest that peripheral inflammation may underpin the well
known detrimental effects of childhood maltreatment and obesity in the course of
BD. Hs-CRP data are difficult to interpret if they are not adjusted for effects
of BMI and age.
PMID- 28403801
TI - IgA/IgM Responses to Gram-Negative Bacteria are not Associated with Perinatal
Depression, but with Physio-Somatic Symptoms and Activation of the Tryptophan
Catabolite Pathway at the End of Term and Postnatal Anxiety.
AB - Evidence has implicated the translocation of commensal Gram-negative bacteria
(Gram-B) due to leaky gut in the pathophysiology of depression and physio-somatic
symptoms (e.g. fatigue, pain, irritable bowel syndrome, malaise, etc.). In
addition, the leaky gut may contribute to immune-inflammatory activation and
oxidative stress. This study investigated whether bacterial translocation is
associated with perinatal depression and anxiety scores and with prenatal physio
somatic symptoms and immune-inflammatory biomarkers, including the tryptophan
catabolite (TRYCAT) pathway. Data were collected in pregnant women at the end of
term (T1) and 4-6 weeks after delivery (T2) as well as in non-pregnant controls.
We examined the associations between serum IgM/IgA responses to Gram-B at the end
of term and depression (Edinburgh Postnatal Depression Scale -EPDS) and anxiety
(Spielberger's State Anxiety Inventory -STAI) symptoms. Levels of C-reactive
protein, zinc, haptoglobin, hematocrit and IgA/IgM responses to 9 TRYCATs were
also measured. No significant associations of the IgA/IgM responses to Gram-B
with prenatal depression and anxiety were observed. Increased IgA/IgM responses
to Gram-B predict higher levels of haptoglobin, hematocrit and TRYCATs, in
particular quinolinic acid and the quinolinic acid / kynurenic acid ratio. IgA
responses to Gram-B were significantly lowered in pregnant women compared to age
matched non-pregnant women, while IgM responses were significantly elevated in
participants with alcohol consumption. Physio-somatic symptoms at the end of term
were significantly associated with IgM responses to Klebsiella pneumonia.
Postnatal anxiety was significantly predicted by IgA responses to Pseudomonas
aeruginosa. In conclusion, our findings suggest that pregnancy may protect
against bacterial translocation, while alcohol use may increase bacterial
translocation. The results suggest that end of term mucosa-derived immune
responses to Gram-B contribute to immune activation, physio-somatic symptoms at
the end of term and postnatal anxiety.
PMID- 28403802
TI - Effects of Fenofibrate on the Expression of Small Heterodimer Partner (SHP) and
Cytochrome P450 (CYP) 2D6.
AB - BACKGROUND: Cytochrome P450 (CYP) 2D6 is a major drug-metabolizing enzyme,
responsible for eliminating 25% of marketed drugs. We recently identified SHP as
a negative regulator of CYP2D6 expression and showed that factors that alter SHP
expression influence CYP2D6 expression. Fenofibrate, an agonist of peroxisome
proliferator-activated receptor alpha(PPARalpha), has been previously reported to
upregulate SHP expression in the mouse liver. The objective of this study was to
determine whether fenofibrate decreases CYP2D6 expression via upregulating SHP
expression. METHODS: CYP2D6-humanized transgenic mice were administered with
fenofibrate (100 mg/kg/day intraperitoneally for 5 days) or vehicle control.
Hepatic mRNA and protein expression levels of CYP2D6 and SHP were measured.
RESULTS: Results showed that while mRNA levels of SHP did not differ between the
groups, protein levels of SHP increased by 2-fold in fenofibrate-treated mice.
Despite the increased SHP protein levels, CYP2D6 expression did not decrease at
the mRNA or protein levels. Similar results were observed in human hepatocytes
treated with fenofibrate. Results from transient transfection and promoter
reporter assays indicate that PPARalpha can transactivate CYP2D6 promoter,
suggesting that the lack of CYP2D6 downregulation by fenofibrate may be in part
due to the activation of CYP2D6 promoter by PPARalpha. CONCLUSION: These results
indicate that fenofibrate has minimal effects on CYP2D6 expression despite
increased SHP expression.
PMID- 28403804
TI - PCR'S NEXT WAVE.
AB - New applications are driving the need for faster, higher fidelity PCR. Nathan
Blow looks at some clever modifications taking PCR to the next level.
PMID- 28403803
TI - Metabolic Profile of Flunitrazepam: Clinical and Forensic Toxicological Aspects.
AB - BACKGROUND: Flunitrazepam (FNZ) is a potent hypnotic, sedative, and amnestic drug
used to treat insomnia and as a pre-anesthetic agent. The illicit practice in
drug-facilitated sexual assault led to important clinical and forensic concerns.
OBJECTIVE: In this work the metabolism of FNZ, and pharmacological- and
toxicological-related effects, were fully reviewed. METHODS: FNZ and related
known metabolizing enzymes and metabolites were searched in books and in PubMed
(U.S. National Library of Medicine) without a limiting period. RESULTS: Major
metabolic pathways include N-demethylation, 3-hydroxylation, nitro-reduction, and
further N-acetylation of the amino group, yielding N-desmethylflunitrazepam, 3
hydroxy-flunitrazepam, 7-aminoflunitrazepam, and 7-acetamidoflunitrazepam,
respectively. A combination of these reactions may lead to the formation of 7
amino-N-desmethylflunitrazepam, 7-acetamido-N-desmethylflunitrazepam, 3- hydroxy
7-aminoflunitrazepam, 3-hydroxy-7-acetamidoflunitrazepam, 3-hydroxy-N
desmethylflunitrazepam and glucuronide conjugates. Genotypic variations in
enzymes, interactions with other drugs or stability of FNZ during storage can
result in large interindividual variability in the toxicological results.
CONCLUSION: It is aimed that knowing the metabolism of FNZ may lead to the
development of new analytical strategies for early detection, since this drug is
typically present in very low concentrations in blood and urine when used to
facilitate sexual assault.
PMID- 28403805
TI - ENTERING THE MATRIX.
AB - Animal cells interact with the extracellular matrix to divide, manage shape, and
migrate. Amber Dance looks at new techniques aimed at revealing how this happens.
PMID- 28403806
TI - Two-color fluorescent cytosine extension assay for the determination of global
DNA methylation.
AB - Here, we present a DNA restriction enzyme-based, fluorescent cytosine extension
assay (CEA) to improve normalization and technical variation among sample-to
sample measurements. The assay includes end-labeling of parallel methylation
sensitive and methylation-insensitive DNA restriction enzyme digests along with
co-purification and subsequent co-measurement of incorporated fluorescence. This
non-radioactive, two-color fluorescent CEA (TCF-CEA) was shown to be a relatively
rapid and accurate, with 3-fold greater precision than the one-color CEA. In
addition, TCF-CEA provided an index of global DNA methylation that was sensitive
to differences >5%. TCF-CEA results were highly correlated with LUminometric
Methylation Assay (LUMA) results using human liver cell lines (HepG2, HepaRG, HC
04) as well as a human liver primary cell culture. Hypomethylation was observed
in cells treated with the de-methylating agent 5-aza-2'-deoxycytidine. These
results demonstrate that TCF-CEA provides a simple method for measuring relative
degrees of global DNA methylation that could potentially be scaled up to higher
throughput formats.
PMID- 28403807
TI - Generating stable cell lines with quantifiable protein production using
CRISPR/Cas9-mediated knock-in.
AB - Cell lines expressing foreign genes have been widely used to produce a variety of
recombinant proteins. However, generating recombinant protein-expressing cell
lines is usually a lengthy process and the resulting protein expression levels
are often inconsistent. Here, we describe an efficient method for making stable
cell lines expressing any recombinant protein of interest in a controllable and
quantifiable manner. We integrate transgenes into specific genomic loci using
CRISPR/Cas9 such that transgene expression is driven by endogenous promoters to
ensure consistent and predictable expression of the recombinant protein.
Expression levels can be predetermined by selecting promoters from genes with the
desired level of expression. To quantify recombinant protein expression, a
protein quantitation reporter (PQR) is incorporated between the endogenous and
foreign genes. The PQR allows equimolar production of the endogenous protein, the
recombinant protein, and a fluorescent reporter. As a result, expression levels
of both the endogenous and recombinant proteins can be continuously monitored
using fluorescence.
PMID- 28403808
TI - ImageJ macros for the user-friendly analysis of soft-agar and wound-healing
assays.
AB - Recent advances in biological imaging techniques and the enormous amount of data
they generate call for the development of computational tools for efficient and
reliable high-throughput analysis. Several software applications with this
functionality are available, and one of the most commonly used is ImageJ. Here,
we present two independent macros (WH_NJ and SA_NJ) for automating and
facilitating the analysis of images acquired from two in vitro assays frequently
used in cancer studies and drug screening: the wound-healing and soft-agar
assays. These two algorithms combine, in a single command, the steps required for
the individual analysis of each image using ImageJ. WH_NJ and SA_NJ allow fast,
reproducible data analysis without the experimental bias inherent in manual
analyses, thus guaranteeing the robustness and reliability of the results.
PMID- 28403809
TI - Effective DNA fragmentation technique for simple sequence repeat detection with a
microsatellite-enriched library and high-throughput sequencing.
AB - Two different techniques for genomic DNA fragmentation before microsatellite
enriched library construction-restriction enzyme (NlaIII and MseI) digestion and
sonication-were compared to examine their effects on simple sequence repeat (SSR)
detection using high-throughput sequencing. Tens of thousands of SSR regions from
5 species of the plant family Myrtaceae were detected when the output of
individual samples was >1 million paired-end reads. Comparison of the two DNA
fragmentation techniques showed that restriction enzyme digestion was superior to
sonication for identification of heterozygous genotypes, whereas sonication was
superior for detection of various SSR flanking regions with both species-specific
and common characteristics. Therefore, choosing the most suitable DNA
fragmentation method depends on the type of analysis that is planned.
PMID- 28403810
TI - Transient dominant host-range selection using Chinese hamster ovary cells to
generate marker-free recombinant viral vectors from vaccinia virus.
AB - Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for
vaccine development that are also useful as research tools. Two common methods
for selection during construction of rVACV clones are (i) co-insertion of drug
resistance or reporter protein genes, which requires the use of additional
selection drugs or detection methods, and (ii) dominant host-range selection. The
latter uses VACV variants rendered replication-incompetent in host cell lines by
the deletion of host-range genes. Replicative ability is restored by co-insertion
of the host-range genes, providing for dominant selection of the recombinant
viruses. Here, we describe a new method for the construction of rVACVs using the
cowpox CP77 protein and unmodified VACV as the starting material. Our selection
system will expand the range of tools available for positive selection of rVACV
during vector construction, and it is substantially more high-fidelity than
approaches based on selection for drug resistance.
PMID- 28403811
TI - Estimating the standardized incidence ratio (SIR) with incomplete follow-up data.
AB - BACKGROUND: A standard parameter to compare the disease incidence of a cohort
relative to the population is the standardized incidence ratio (SIR). For
statistical inference is commonly assumed that the denominator, the expected
number of cases, is fixed. If a disease registry is available, incident cases can
sometimes be identified by linkage with the registry, however, registries may not
contain information on migration or death from other causes. A complete follow-up
with a population registry may not be possible. In that case, end-of-follow-up
date and therefore, exact person-years of observation are unknown. METHODS: We
have developed a method to estimate the observation times and to derive the
expected number of cases using population data on mortality and migration rates.
We investigate the impact of the underlying assumptions with a sensitivity
analysis. RESULTS: The method provides a useful estimate of the SIR. We
illustrate the method with a numerical example, a simulation study and with a
study on standardized cancer incidence ratios in a cohort of migrants relative to
the German population. We show that the additional variance induced by the
estimation method is small, so that standard methods for inference can be
applied. CONCLUSIONS: Estimation of the observation time is possible for cohort
studies with incomplete follow-up.
PMID- 28403812
TI - Infections and cancer: the "fifty shades of immunity" hypothesis.
AB - BACKGROUND: Since the beginning of the twentieth century, infection has emerged
as a fundamental aspect of cancer causation with a growing number of pathogens
recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted
considerable interest as possible agents of tumor destruction. DISCUSSION: Lost
in the dichotomy between oncogenic and oncolytic agents, the indirect influence
of infectious organisms on carcinogenesis has been largely unexplored. We
describe the various ways - from functional aspects to evolutionary
considerations such as modernity mismatches - by which infectious organisms could
interfere with oncogenic processes through immunity. Finally, we discuss how
acknowledging these interactions might impact public health approaches and
suggest new guidelines for therapeutic and preventive strategies both at
individual and population levels. Infectious organisms, that are not oncogenic
neither oncolytic, may play a significant role in carcinogenesis, suggesting the
need to increase our knowledge about immune interactions between infections and
cancer.
PMID- 28403813
TI - Beliefs and practices during pregnancy, post-partum and in the first days of an
infant's life in rural Cambodia.
AB - BACKGROUND: The aim of this study was to record the beliefs, practices during
pregnancy, post-partum and in the first few days of an infant's life, held by a
cross section of the community in rural Cambodia to determine beneficial
community interventions to improve early neonatal health. METHODS: Qualitative
study design with data generated from semi structured interviews (SSI) and focus
group discussions (FGD). Data were analysed by thematic content analysis, with an
a priori coding structure developed using available relevant literature. Further
reading of the transcripts permitted additional coding to be performed in vivo.
This study was conducted in two locations, firstly the Angkor Hospital for
Children and secondarily in five villages in Sotnikum, Siem Reap Province,
Cambodia. RESULTS: A total of 20 participants underwent a SSIs (15 in hospital
and five in the community) and six (three in hospital and three in the community;
a total of 58 participants) FGDs were conducted. Harmful practices that occurred
in the past (for example: discarding colostrum and putting mud on the umbilical
stump) were not described as being practiced. Village elders did not enforce
traditional views. Parents could describe signs of illness and felt responsible
to seek care for their child even if other family members disagreed, however
participants were unaware of the signs or danger of neonatal jaundice. Cost of
transportation was the major barrier to healthcare that was identified.
CONCLUSIONS: In the population examined, traditional practices in late pregnancy
and the post-partum period were no longer commonly performed. However, jaundice,
a potentially serious neonatal condition, was not recognised. Community neonatal
interventions should be tailored to the populations existing practice and
knowledge.
PMID- 28403816
TI - Substantial out-of-pocket expenditure on maternity care practitioner
consultations and treatments during pregnancy: estimates from a nationally
representative sample of pregnant women in Australia.
AB - BACKGROUND: A wide range of health care options are utilised by pregnant women in
Australia. The out-of-pocket costs of maternity care in Australia vary depending
on many factors including model of care utilised, health insurance coverage, and
women's decision to access health services outside of conventional maternity care
provision. METHODS: Women from the 1973-78 cohort of the Australian Longitudinal
Study on Women's Health (ALSWH) who identified as pregnant or as recently having
given birth in 2009 were invited to complete a sub-study questionnaire
investigating health service utilisation during their most recent pregnancy.
RESULTS: A total of 1,835 women agreed to participate in the sub-study. The
majority of women (99.8%) consulted with a conventional health care practitioner
during pregnancy, 49.4% consulted with a complementary and alternative medicine
practitioner at least once during pregnancy and 89.6% of the women used a
complementary and alternative medicine product. Women reported an average of
AUD$781.10 in out-of-pocket expenses for consultations with conventional health
care practitioners, AUD$185.40 in out-of-pocket expenses for consultations with
complementary and alternative medicine practitioners and AUD$179.60 in out-of
pocket expenses for complementary and alternative medicine products. From the
study data we estimate Australian pregnant women spend over AUD$337 M on out-of
pocket health services. CONCLUSION: While the majority of pregnant women in
Australia may obtain health services via the publically-funded health care system
and/or private health insurance coverage, our analysis identifies substantial out
of-pocket expenditure for health care by pregnant women - a trend in public
spending for maternity care of importance to policy makers, health
administrators, and health professionals.
PMID- 28403814
TI - Divergent and convergent modes of interaction between wheat and Puccinia graminis
f. sp. tritici isolates revealed by the comparative gene co-expression network
and genome analyses.
AB - BACKGROUND: Two opposing evolutionary constraints exert pressure on plant
pathogens: one to diversify virulence factors in order to evade plant defenses,
and the other to retain virulence factors critical for maintaining a compatible
interaction with the plant host. To better understand how the diversified
arsenals of fungal genes promote interaction with the same compatible wheat line,
we performed a comparative genomic analysis of two North American isolates of
Puccinia graminis f. sp. tritici (Pgt). RESULTS: The patterns of inter-isolate
divergence in the secreted candidate effector genes were compared with the levels
of conservation and divergence of plant-pathogen gene co-expression networks
(GCN) developed for each isolate. Comprative genomic analyses revealed
substantial level of interisolate divergence in effector gene complement and
sequence divergence. Gene Ontology (GO) analyses of the conserved and unique
parts of the isolate-specific GCNs identified a number of conserved host pathways
targeted by both isolates. Interestingly, the degree of inter-isolate sub-network
conservation varied widely for the different host pathways and was positively
associated with the proportion of conserved effector candidates associated with
each sub-network. While different Pgt isolates tended to exploit similar wheat
pathways for infection, the mode of plant-pathogen interaction varied for
different pathways with some pathways being associated with the conserved set of
effectors and others being linked with the diverged or isolate-specific
effectors. CONCLUSIONS: Our data suggest that at the intra-species level pathogen
populations likely maintain divergent sets of effectors capable of targeting the
same plant host pathways. This functional redundancy may play an important role
in the dynamic of the "arms-race" between host and pathogen serving as the basis
for diverse virulence strategies and creating conditions where mutations in
certain effector groups will not have a major effect on the pathogen's ability to
infect the host.
PMID- 28403815
TI - Gamma probe and ultrasound guided fine needle aspiration cytology of the sentinel
node (GULF) trial - overview of the literature, pilot and study protocol.
AB - BACKGROUND: Sentinel node (SN) biopsy (SNB) detects clinically occult metastases
of breast cancer and melanoma in 20-30%. Wound infections, seroma and lymph edema
occur in up to 10%. Targeted ultrasound (US) of the SN, (with fine needle
aspiration cytology (FNAC) if appropriate) has been investigated as a minimally
invasive alternative, but reported sensitivity rates are too low to replace SNB.
Our hypothesis is that the use of a handheld gamma probe concomitant with US may
improve sensitivity. Our aim is to provide an overview of the current literature
on preoperative nodal staging of clinical N0 melanoma patients, report on a
pilot, and present a study protocol for a minimally invasive alternative to the
SNB: Gamma probe and Ultrasound guided Fine needle aspiration cytology of the
sentinel node (GULF trial). METHODS: The GULF trial is a multicenter open single
arm observational trial. Newly diagnosed cT1b-4N0M0 cutaneous melanoma or cT1
3N0M0 breast cancer patients, aged >18 years, presenting for SNB are eligible.
120 patients will be included for preoperative targeted gamma probe guided US and
FNAC of the SN. Afterwards all patients proceed to surgical SNB. Primary endpoint
is the sensitivity of FNAC. Secondary endpoints include SN identification rate
and the histopathological compatibility of Core Needle Biopsy and FNAC vs. SNB.
Secondary endpoints were investigated in a pilot with 10 FNACs and marker
placements, and 10 FNACs combined with Core Needle Biopsy. RESULTS: A pilot in 20
patients showed that SN identification rate was 90%, supporting the feasibility
of this technique. DISCUSSION: There is broad experience with US (in combination
with FNAC) prior to SNB, but sensitivity and specificity are too low to
completely abandon SNB. Promising alternative techniques potentially will replace
SNB in the future but more evidence is needed in the form of prospective studies.
Accurate identification of the SN for US-FNAC has been proven feasible in our
pilot. When adequate sensitivity can be reached, US-FNAC provides a minimally
invasive alternative for the surgical SNB procedure. TRIAL REGISTRATION: The GULF
trial is registered in the Netherlands Trial Registry (NTR), ID: NRT5193 . May
1st 2015.
PMID- 28403817
TI - Homology to peptide pattern for annotation of carbohydrate-active enzymes and
prediction of function.
AB - BACKGROUND: Carbohydrate-active enzymes are found in all organisms and
participate in key biological processes. These enzymes are classified in 274
families in the CAZy database but the sequence diversity within each family makes
it a major task to identify new family members and to provide basis for
prediction of enzyme function. A fast and reliable method for de novo annotation
of genes encoding carbohydrate-active enzymes is to identify conserved peptides
in the curated enzyme families followed by matching of the conserved peptides to
the sequence of interest as demonstrated for the glycosyl hydrolase and the lytic
polysaccharide monooxygenase families. This approach not only assigns the enzymes
to families but also provides functional prediction of the enzymes with high
accuracy. RESULTS: We identified conserved peptides for all enzyme families in
the CAZy database with Peptide Pattern Recognition. The conserved peptides were
matched to protein sequence for de novo annotation and functional prediction of
carbohydrate-active enzymes with the Hotpep method. Annotation of protein
sequences from 12 bacterial and 16 fungal genomes to families with Hotpep had an
accuracy of 0.84 (measured as F1-score) compared to semiautomatic annotation by
the CAZy database whereas the dbCAN HMM-based method had an accuracy of 0.77 with
optimized parameters. Furthermore, Hotpep provided a functional prediction with
86% accuracy for the annotated genes. Hotpep is available as a stand-alone
application for MS Windows. CONCLUSIONS: Hotpep is a state-of-the-art method for
automatic annotation and functional prediction of carbohydrate-active enzymes.
PMID- 28403818
TI - sRNAs as possible regulators of retrotransposon activity in Cryptococcus gattii
VGII.
AB - BACKGROUND: The absence of Argonaute genes in the fungal pathogen Cryptococcus
gattii R265 and other VGII strains indicates that yeasts of this genotype cannot
have a functional RNAi pathway, an evolutionarily conserved gene silencing
mechanism performed by small RNAs. The success of the R265 strain as a pathogen
that caused the Pacific Northwest and Vancouver Island outbreaks may imply that
RNAi machinery loss could be beneficial under certain circumstances during
evolution. As a result, a hypermutant phenotype would be created with high rates
of genome retrotransposition, for instance. This study therefore aimed to
evaluate in silicio the effect of retrotransposons and their control mechanisms
by small RNAs on genomic stability and synteny loss of C. gattii R265 through
retrotransposons sequence comparison and orthology analysis with other 16 C.
gattii genomic sequences available. RESULTS: Retrotransposon mining identified a
higher sequence count to VGI genotype compared to VGII, VGIII, and VGIV. However,
despite the lower retrotransposon number, VGII exhibited increased synteny loss
and genome rearrangement events. RNA-Seq analysis indicated highly expressed
retrotransposons as well as sRNA production. CONCLUSIONS: Genome rearrangement
and synteny loss may suggest a greater retrotransposon mobilization caused by
RNAi pathway absence, but the effective presence of sRNAs that matches
retrotransposon sequences means that an alternative retrotransposon silencing
mechanism could be active in genomic integrity maintenance of C. gattii VGII
strains.
PMID- 28403819
TI - QTL mapping for fruit quality in Citrus using DArTseq markers.
AB - BACKGROUND: Citrus breeding programs have many limitations associated with the
species biology and physiology, requiring the incorporation of new
biotechnological tools to provide new breeding possibilities. Diversity Arrays
Technology (DArT) markers, combined with next-generation sequencing, have wide
applicability in the construction of high-resolution genetic maps and in
quantitative trait locus (QTL) mapping. This study aimed to construct an
integrated genetic map using full-sib progeny derived from Murcott tangor and
Pera sweet orange and DArTseqTM molecular markers and to perform QTL mapping of
twelve fruit quality traits. A controlled Murcott x Pera crossing was conducted
at the Citrus Germplasm Repository at the Sylvio Moreira Citrus Centre of the
Agronomic Institute (IAC) located in Cordeiropolis, SP, in 1997. In 2012, 278 F1
individuals out of a family of 312 confirmed hybrid individuals were analyzed for
fruit traits and genotyped using the DArTseq markers. Using OneMap software to
obtain the integrated genetic map, we considered only the DArT loci that showed
no segregation deviation. The likelihood ratio and the genomic information from
the available Citrus sinensis L. Osbeck genome were used to determine the linkage
groups (LGs). RESULTS: The resulting integrated map contained 661 markers in 13
LGs, with a genomic coverage of 2,774 cM and a mean density of 0.23 markers/cM.
The groups were assigned to the nine Citrus haploid chromosomes; however, some of
the chromosomes were represented by two LGs due the lack of information for a
single integration, as in cases where markers segregated in a 3:1 fashion. A
total of 19 QTLs were identified through composite interval mapping (CIM) of the
12 analyzed fruit characteristics: fruit diameter (cm), height (cm),
height/diameter ratio, weight (g), rind thickness (cm), segments per fruit, total
soluble solids (TSS, %), total titratable acidity (TTA, %), juice content (%),
number of seeds, TSS/TTA ratio and number of fruits per box. The genomic sequence
(pseudochromosomes) of C. sinensis was compared to the genetic map, and synteny
was clearly identified. Further analysis of the map regions with the highest LOD
scores enabled the identification of putative genes that could be associated with
the fruit quality characteristics. CONCLUSION: An integrated linkage map of
Murcott tangor and Pera sweet orange using DArTseqTM molecular markers was
established and it was useful to perform QTL mapping of twelve fruit quality
traits. The next generation sequences data allowed the comparison between the
linkage map and the genomic sequence (pseudochromosomes) of C. sinensis and the
identification of genes that may be responsible for phenotypic traits in Citrus.
The obtained linkage map was used to assign sequences that had not been
previously assigned to a position in the reference genome.
PMID- 28403820
TI - Characterization of genome-wide segmental duplications reveals a common genomic
feature of association with immunity among domestic animals.
AB - BACKGROUND: Segmental duplications (SDs) commonly exist in plant and animal
genomes, playing crucial roles in genomic rearrangement, gene innovation and the
formation of copy number variants. However, they have received little attention
in most livestock species. RESULTS: Aiming at characterizing SDs across the
genomes of diverse livestock species, we mapped genome-wide SDs of horse, rabbit,
goat, sheep and chicken, and also enhanced the existing SD maps of cattle and pig
genomes based on the most updated genome assemblies. We adopted two different
detection strategies, whole genome analysis comparison and whole genome shotgun
sequence detection, to pursue more convincing findings. Accordingly we identified
SDs for each species with the length of from 21.7 Mb to 164.1 Mb, and 807 to
4,560 genes were harboured within the SD regions across different species. More
interestingly, many of these SD-related genes were involved in the process of
immunity and response to external stimuli. We also found the existence of 59
common genes within SD regions in all studied species except goat. These common
genes mainly consisted of both UDP glucuronosyltransferase and Interferon alpha
families, implying the connection between SDs and the evolution of these gene
families. CONCLUSIONS: Our findings provide insights into livestock genome
evolution and offer rich genomic sources for livestock genomic research.
PMID- 28403822
TI - Provider and patient perspectives on opioids and alternative treatments for
managing chronic pain: a qualitative study.
AB - BACKGROUND: Current literature describes the limits and pitfalls of using opioid
pharmacotherapy for chronic pain and the importance of identifying alternatives.
The objective of this study was to identify the practical issues patients and
providers face when accessing alternatives to opioids, and how multiple parties
view these issues. METHODS: Qualitative data were gathered to evaluate the
outcomes of acupuncture and chiropractic (A/C) services for chronic
musculoskeletal pain (CMP) using structured interview guides among patients with
CMP (n = 90) and primary care providers (PCPs) (n = 25) purposively sampled from
a managed care health care system as well as from contracted community A/C
providers (n = 14). Focus groups and interviews were conducted patients with CMP
with varying histories of A/C use. Plan PCPs and contracted A/C providers took
part in individual interviews. All participants were asked about their
experiences managing chronic pain and experience with and/or attitudes about A/C
treatment. Audio recordings were transcribed and thematically coded. A summarized
version of the focus group/interview guides is included in the Additional file 1.
RESULTS: We identified four themes around opioid use: (1) attitudes toward use of
opioids to manage chronic pain; (2) the limited alternative options for chronic
pain management; (3) the potential of A/C care as a tool to help manage pain; and
(4) the complex system around chronic pain management. Despite widespread
dissatisfaction with opioid medications for pain management, many practical
barriers challenged access to other options. Most of the participants' perceived
A/C care as helpful for short term pain relief. We identified that problems with
timing, expectations, and plan coverage limited A/C care potential for pain
relief treatment. CONCLUSIONS: These results suggest that education about
realistic expectations for chronic pain management and therapy options, as well
as making A/C care more easily accessible, might lead to more satisfaction for
patients and providers, and provide important input to policy makers. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01345409 , date of registration 28/4/2011.
PMID- 28403823
TI - Empirical Bayes method for reducing false discovery rates of correlation matrices
with block diagonal structure.
AB - BACKGROUND: Correlation matrices are important in inferring relationships and
networks between regulatory or signalling elements in biological systems. With
currently available technology sample sizes for experiments are typically small,
meaning that these correlations can be difficult to estimate. At a genome-wide
scale estimation of correlation matrices can also be computationally demanding.
RESULTS: We develop an empirical Bayes approach to improve covariance estimates
for gene expression, where we assume the covariance matrix takes a block diagonal
form. Our method shows lower false discovery rates than existing methods on
simulated data. Applied to a real data set from Bacillus subtilis we demonstrate
it's ability to detecting known regulatory units and interactions between them.
CONCLUSIONS: We demonstrate that, compared to existing methods, our method is
able to find significant covariances and also to control false discovery rates,
even when the sample size is small (n=10). The method can be used to find
potential regulatory networks, and it may also be used as a pre-processing step
for methods that calculate, for example, partial correlations, so enabling the
inference of the causal and hierarchical structure of the networks.
PMID- 28403821
TI - Defining the transcriptomic landscape of the developing enteric nervous system
and its cellular environment.
AB - BACKGROUND: Motility and the coordination of moving food through the
gastrointestinal tract rely on a complex network of neurons known as the enteric
nervous system (ENS). Despite its critical function, many of the molecular
mechanisms that direct the development of the ENS and the elaboration of neural
network connections remain unknown. The goal of this study was to
transcriptionally identify molecular pathways and candidate genes that drive
specification, differentiation and the neural circuitry of specific neural
progenitors, the phox2b expressing ENS cell lineage, during normal enteric
nervous system development. Because ENS development is tightly linked to its
environment, the transcriptional landscape of the cellular environment of the
intestine was also analyzed. RESULTS: Thousands of zebrafish intestines were
manually dissected from a transgenic line expressing green fluorescent protein
under the phox2b regulatory elements [Tg(phox2b:EGFP) w37 ]. Fluorescence
activated cell sorting was used to separate GFP-positive phox2b expressing ENS
progenitor and derivatives from GFP-negative intestinal cells. RNA-seq was
performed to obtain accurate, reproducible transcriptional profiles and the
unbiased detection of low level transcripts. Analysis revealed genes and pathways
that may function in ENS cell determination, genes that may be identifiers of
different ENS subtypes, and genes that define the non-neural cellular
microenvironment of the ENS. Differential expression analysis between the two
cell populations revealed the expected neuronal nature of the phox2b expressing
lineage including the enrichment for genes required for neurogenesis and
synaptogenesis, and identified many novel genes not previously associated with
ENS development. Pathway analysis pointed to a high level of G-protein coupled
pathway activation, and identified novel roles for candidate pathways such as the
Nogo/Reticulon axon guidance pathway in ENS development. CONCLUSION: We report
the comprehensive gene expression profiles of a lineage-specific population of
enteric progenitors, their derivatives, and their microenvironment during normal
enteric nervous system development. Our results confirm previously implicated
genes and pathways required for ENS development, and also identify scores of
novel candidate genes and pathways. Thus, our dataset suggests various potential
mechanisms that drive ENS development facilitating characterization and discovery
of novel therapeutic strategies to improve gastrointestinal disorders.
PMID- 28403824
TI - Using a quality improvement model to enhance providers' performance in maternal
and newborn health care: a post-only intervention and comparison design.
AB - BACKGROUND: The Standards Based Management and Recognition (SBM-R(c)) approach to
quality improvement has been implemented in Ethiopia to strengthen routine
maternal and newborn health (MNH) services. This evaluation assessed the effect
of the intervention on MNH providers' performance of routine antenatal care
(ANC), uncomplicated labor and delivery and immediate postnatal care (PNC)
services. METHODS: A post-only evaluation design was conducted at three hospitals
and eight health centers implementing SBM-R and the same number of comparison
health facilities. Structured checklists were used to observe MNH providers'
performance on ANC (236 provider-client interactions), uncomplicated labor and
delivery (226 provider-client interactions), and immediate PNC services in the
six hours after delivery (232 provider-client interactions); observations were
divided equally between intervention and comparison groups. Main outcomes were
provider performance scores, calculated as the percentage of essential tasks in
each service area completed by providers. Multilevel analysis was used to
calculate adjusted mean percentage performance scores and standard errors to
compare intervention and comparison groups. RESULTS: There was no statistically
significant difference between intervention and comparison facilities in overall
mean performance scores for ANC services (63.4% at intervention facilities versus
61.0% at comparison facilities, p = 0.650) or in any specific ANC skill area. MNH
providers' overall mean performance score for uncomplicated labor and delivery
care was 11.9 percentage points higher in the intervention than in the comparison
group (77.5% versus 65.6%; p = 0.002). Overall mean performance scores for
immediate PNC were 22.2 percentage points higher at intervention than at
comparison facilities (72.8% versus 50.6%; p = 0.001); and there was a
significant difference of 22 percentage points between intervention and
comparison facilities for each PNC skill area: care for the newborn and health
check for the mother. CONCLUSIONS: The SBM-R quality improvement intervention
made a significant positive impact on MNH providers' performance during labor and
delivery and immediate PNC services, but not during ANC services. Scaling up the
intervention to other facilities and regions may increase the availability of
good quality MNH services across Ethiopia. The findings will also guide
implementation of the government's five-year (2015-2020) health sector
transformation plan and health care quality strategies needed to meet the
country's MNH goals.
PMID- 28403826
TI - Erratum to: Multidrug resistance protein MdtM adds to the repertoire of
antiporters involved in alkaline pH homeostasis in Escherichia coli.
PMID- 28403825
TI - Disparities in HIV and syphilis prevalence and risk factors between older male
clients with and without steady sex partners in southwestern rural China.
AB - BACKGROUND: Heterosexual intercourse accounted for 93% of reported HIV cases in
Guangxi, and Guangxi had 10% of China's total number of reported HIV cases. Older
men are particularly vulnerable to STIs, for example, 46% of Guangxi's HIV cases
were men over 50 years of age. As this is an under-studied population in China,
effective prevention and control policies have yet to be developed. Thus, the aim
of this study was to use a large-scale cross-sectional survey to understand the
demographic and behavior factors associated with HIV and syphilis infections
among older male clients of female sex workers (FSWs) in a high epidemic area of
rural Guangxi, China. METHODS: A large-scale cross-sectional survey was conducted
in 2012 among older male clients of FSWs in low-cost commercial sex venues.
Questionnaire interviews were administered to collect sociodemographic and sexual
behavior information. Blood samples were collected for HIV and syphilis infection
tests. RESULTS: Of the 3485 participants, 2509 (72.0%) clients had a steady sex
partner and 976 (28.0%) clients had no steady sex partner. The overall prevalence
of HIV and syphilis infection were 3.0% and 3.2%, respectively. Compared to those
with a steady sex partner, clients with no steady partner had higher odds of HIV
infection (AOR: 1.90, 95% CI: 1.27-2.86), syphilis infection (AOR: 1.53, 95% CI:
1.02-2.30), and having factors associated with HIV or syphilis infection,
including non-commercial casual sex encounters in last month (AOR: 3.29, 95% CI:
2.42-4.46), >10 years of commercial sex history (AOR: 1.31, 95% CI: 1.12-1.53),
>2 incidents of commercial sex in last month (AOR: 1.53, 95% CI: 1.19-1.96), and
aphrodisiac use in last month (AOR: 1.40, 95% CI: 1.16-1.70). Clients with no
steady partner had lower odds of having heterosexual intercourse (AOR: 0.66, 95%
CI: 0.56-0.79), awareness and knowledge of HIV/AIDS (AOR: 0.75, 95% CI: 0.64
0.88), and having had HIV tests (AOR: 0.65, 95% CI: 0.44-0.98). CONCLUSION: Older
male clients of low-cost commercial sex venues in rural southwestern China are at
high risk for HIV and syphilis infection, especially those with no steady sex
partner. Improved interventions are urgently needed for this neglected risk
population.
PMID- 28403827
TI - A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure
hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.
AB - BACKGROUND: Pure hair and nail ectodermal dysplasia (PHNED) is a congenital
disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and
dominant inheritance fashion of PHNED occurs. In literature, to date, five
different forms of PHNED have been reported at molecular level, having three
genes known and two loci with no gene yet. METHODS: In this study, a four
generations consanguineous family of Pakistani origin with autosomal recessive
PHNED was investigated. Affected members exhibited PHNED phenotypes with
involvement of complete hair loss and nail dysplasia. To screen for mutation in
the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries
were sequenced. The 3D models of normal and mutated HOXC13 were predicted by
using homology modeling. RESULTS: Through investigating the family to known loci,
the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address
of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C;
p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of
the family. Due to mutation, loss of hydrogen bonding and difference in potential
energy occurs, which may resulting in alteration of protein function. CONCLUSION:
This is the first mutation reported in homeodomain, while 5th mutation reported
in HOXC13 gene causing PHNED.
PMID- 28403828
TI - Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant
women from the state of Para, Brazil.
AB - BACKGROUND: The present study aimed to describe the genetic diversity of HIV-1,
as well as the resistance profile of the viruses identified in HIV-1 infected
pregnant women under antiretroviral therapy in the state of Para, Northern
Brazil. METHODS: Blood samples were collected from 45 HIV-1 infected pregnant to
determine the virus subtypes according to the HIV-1 protease (PR) gene and part
of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of
these regions. Drug resistance mutations and susceptibility to antiretroviral
drugs were analyzed by the Stanford HIV Drug Resistance Database. RESULTS: Out of
45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR
gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes
B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease
inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring
resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%,
while mutations conferring resistance to non-nucleoside reverse transcriptase
inhibitors were found in 3.3%. CONCLUSIONS: These results showed a low frequency
of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F,
and the persistent low transmission of subtype C in pregnant of the state of
Para, Brazil.
PMID- 28403829
TI - Systemic therapy in younger and elderly patients with advanced biliary cancer:
sub-analysis of ABC-02 and twelve other prospective trials.
AB - BACKGROUND: Outcomes in younger (<40 years) and elderly (>=70 years) patients
with advanced biliary cancer (ABC) receiving palliative chemotherapy are unclear.
This study assessed outcomes in those receiving monotherapy or combination
therapy in thirteen prospective systemic-therapy trials. METHODS: Multivariable
analysis explored the impact of therapy on progression-free (PFS) and overall
survival (OS) in two separate age cohort groups: <70 years and >=70 years, and
<40 years and >=40 years. RESULTS: Overall, 1163 patients were recruited (Jan
1997-Dec 2013). Median age of entire cohort: 63 years (range 23-85); 36 (3%) were
<40, 260 (22%); >=70. Combination therapy was platinum-based in nine studies.
Among patients <40 and >=70 years, 23 (64%) and 182 (70%) received combination
therapy, respectively. Median follow-up was 42 months (95%-CI 37-51). Median PFS
for patients <40 and >=40 years was 3.5 and 5.9 months (P = 0.12), and OS was
10.8 and 9.7 months, respectively (P = 0.55). Median PFS for those <70 and >=70
years was 6.0 and 5.0 months (P = 0.53), and OS was 10.2 and 8.8 months,
respectively (P = 0.08). For the entire cohort, PFS and OS were significantly
better in those receiving combination therapy: Hazard Ratio [HR]-0.66, 95%-CI
0.58-0.76, P < 0.0001 and HR-0.72, 95%-CI 0.63-0.82, P < 0.0001, respectively;
and in patients >=70 years: HR-0.54 (95%-CI 0.38-0.77, P = 0.001) and HR-0.60
(95%-CI 0.43-0.85, P = 0.004), respectively. There was no evidence of interaction
between age and treatment for PFS (P = 0.58, P = 0.66) or OS (P = 0.18, P =
0.75). CONCLUSIONS: In ABC, younger patients are rare, and survival in elderly
patients in receipt of systemic therapy for advanced disease, whether monotherapy
or combination therapy, is similar to that of non-elderly patients, therefore age
alone should not influence decisions regarding treatment.
PMID- 28403830
TI - Effectiveness of Progressive Resistive Exercise (PRE) in the context of HIV:
systematic review and meta-analysis using the Cochrane Collaboration protocol.
AB - BACKGROUND: HIV is increasingly considered a chronic illness. More individuals
are living longer and aging with the health-related consequences associated with
HIV and multi-morbidity. Exercise is a self-management approach that can promote
health for people aging with HIV. We examined the safety and effectiveness of
progressive resistive exercise (PRE) interventions on immunological, virological,
cardiorespiratory, strength, weight, body composition, and psychological outcomes
in adults living with HIV. METHODS: We conducted a systematic review using the
Cochrane Collaboration protocol. Searching databases up to April 2013, we
included randomized controlled trials that compared PRE with no exercise or
another intervention performed at least three times per week for at least four
weeks with adults living with HIV. Two reviewers independently determined study
eligibility. We extracted data from included studies and assessed risk of bias
using the Cochrane Collaboration risk of bias tool. Meta-analyses were conducted
using random effects models with Review Manager (RevMan) computer software.
RESULTS: Twenty studies met inclusion criteria (n = 764 participants at study
completion); the majority of participants were men (77%) taking antiretroviral
therapy (14/20 included studies). Exercise interventions included PRE alone (8
studies) or a combination of resistive and aerobic exercise (12 studies) ranging
from 6 to 52 weeks in duration. Thirty-four meta-analyses were performed. Results
demonstrated statistically significant improvements in cardiorespiratory status
(maximum oxygen consumption, exercise time), strength (chest press, knee
flexion), weight, and body composition (arm and thigh girth, leg muscle area)
among exercisers versus non-exercisers. We found no significant differences in
change in CD4 count and viral load. We were unable to perform meta-analyses for
psychological outcomes however results from individual studies demonstrated
improvements in health-related quality of life with exercisers compared with non
exercisers. CONCLUSIONS: Performing progressive resistive exercise (PRE) or a
combination of resistive and aerobic exercise at least three times per week for
at least six weeks is safe and can lead to improvements in cardiorespiratory
fitness, strength, weight, and body composition for adults with HIV. Exercise may
be considered a safe and beneficial for enhancing the health of medically stable
adults aging with HIV.
PMID- 28403831
TI - The role of Tre6P and SnRK1 in maize early kernel development and events leading
to stress-induced kernel abortion.
AB - BACKGROUND: Drought stress during flowering is a major contributor to yield loss
in maize. Genetic and biotechnological improvement in yield sustainability
requires an understanding of the mechanisms underpinning yield loss. Sucrose
starvation has been proposed as the cause for kernel abortion; however, potential
targets for genetic improvement have not been identified. Field and greenhouse
drought studies with maize are expensive and it can be difficult to reproduce
results; therefore, an in vitro kernel culture method is presented as a proxy for
drought stress occurring at the time of flowering in maize (3 days after
pollination). This method is used to focus on the effects of drought on kernel
metabolism, and the role of trehalose 6-phosphate (Tre6P) and the sucrose non
fermenting-1-related kinase (SnRK1) as potential regulators of this response.
RESULTS: A precipitous drop in Tre6P is observed during the first two hours after
removing the kernels from the plant, and the resulting changes in transcript
abundance are indicative of an activation of SnRK1, and an immediate shift from
anabolism to catabolism. Once Tre6P levels are depleted to below 1 nmol?g-1 FW in
the kernel, SnRK1 remained active throughout the 96 h experiment, regardless of
the presence or absence of sucrose in the medium. Recovery on sucrose enriched
medium results in the restoration of sucrose synthesis and glycolysis.
Biosynthetic processes including the citric acid cycle and protein and starch
synthesis are inhibited by excision, and do not recover even after the re
addition of sucrose. It is also observed that excision induces the transcription
of the sugar transporters SUT1 and SWEET1, the sucrose hydrolyzing enzymes CELL
WALL INVERTASE 2 (INCW2) and SUCROSE SYNTHASE 1 (SUSY1), the class II TREHALOSE
PHOSPHATE SYNTHASES (TPS), TREHALASE (TRE), and TREHALOSE PHOSPHATE PHOSPHATASE
(ZmTPPA.3), previously shown to enhance drought tolerance (Nuccio et al., Nat
Biotechnol (October 2014):1-13, 2015). CONCLUSIONS: The impact of kernel excision
from the ear triggers a cascade of events starting with the precipitous drop in
Tre6P levels. It is proposed that the removal of Tre6P suppression of SnRK1
activity results in transcription of putative SnRK1 target genes, and the
metabolic transition from biosynthesis to catabolism. This highlights the
importance of Tre6P in the metabolic response to starvation. We also present
evidence that sugars can mediate the activation of SnRK1. The precipitous drop in
Tre6P corresponds to a large increase in transcription of ZmTPPA.3, indicating
that this specific enzyme may be responsible for the de-phosphorylation of Tre6P.
The high levels of Tre6P in the immature embryo are likely important for
preventing kernel abortion.
PMID- 28403832
TI - Centering and Racial Disparities (CRADLE study): rationale and design of a
randomized controlled trial of centeringpregnancy and birth outcomes.
AB - BACKGROUND: In the United States, preterm birth (PTB) before 37 weeks gestational
age occurs at an unacceptably high rate, and large racial disparities persist. To
date, medical and public health interventions have achieved limited success in
reducing rates of PTB. Innovative changes in healthcare delivery are needed to
improve pregnancy outcomes. One such model is CenteringPregnancy group prenatal
care (GPNC), in which individual physical assessments are combined with
facilitated group education and social support. Most existing studies in the
literature on GPNC are observational. Although the results are promising, they
are not powered to detect differences in PTB, do not address the racial disparity
in PTB, and do not include measures of hypothesized mediators that are
theoretically based and validated. The aims of this randomized controlled trial
(RCT) are to compare birth outcomes as well as maternal behavioral and
psychosocial outcomes by race among pregnant women who participate in GPNC to
their counterparts in individual prenatal care (IPNC) and to investigate whether
improving women's behavioral and psychosocial outcomes will explain the potential
benefits of GPNC on birth outcomes and racial disparities. METHODS/DESIGN: This
is a single site RCT study at Greenville Health System in South Carolina. Women
are eligible if they are between 14-45 years old and enter prenatal care before
20 6/7 weeks of gestational age. Eligible, consenting women will be randomized
1:1 into GPNC group or IPNC group, stratified by race. Women allocated to GPNC
will attend 2-h group prenatal care sessions according to the standard curriculum
provided by the Centering Healthcare Institute, with other women due to deliver
in the same month. Women allocated to IPNC will attend standard, traditional
individual prenatal care according to standard clinical guidelines. Patients in
both groups will be followed up until 12 weeks postpartum. DISCUSSION: Findings
from this project will provide rigorous scientific evidence on the role of GPNC
in reducing the rate of PTB, and specifically in reducing racial disparities in
PTB. Establishing the improved effect of GPNC on pregnancy and birth outcomes can
change the way healthcare is delivered, particularly with populations with higher
rates of PTB. TRIAL REGISTRATION: NCT02640638 Date Registered: 12/20/2015.
PMID- 28403833
TI - Maternal and fetal outcomes of uterine rupture and factors associated with
maternal death secondary to uterine rupture.
AB - BACKGROUND: Maternal mortality and morbidity are the priority agenda for sub
Saharan Africa including Ethiopia. Uterine rupture is the leading cause of
maternal and fetal death in developing countries. Limited evidence is available
on the magnitude of uterine rupture; maternal and fetal outcomes of uterine
rupture and factors associated with maternal death secondary to uterine rupture
in Ethiopia. This study aimed to assess the magnitude of uterine rupture;
maternal and fetal outcome of uterine rupture and factors associated with
maternal death secondary to uterine rupture in Debremarkos Referral Hospital,
Northwest Ethiopia. METHODS: An institutional-based cross-sectional study was
conducted in December 2015 in Debremarkos referral hospital, Northwest Ethiopia.
A total of 242 records of mothers with uterine rupture at Debremarkos referral
Hospital during the year 2011-2014 were included in the study. Secondary data was
collected from the records of mothers admitted for the management of uterine
rupture. Descriptive statistics were performed to characterize the study
population. Bivariate and multivariable logistic regression model was fitted to
identify factors associated with maternal death secondary to uterine rupture.
Odds ratio with 95% confidence interval was computed to determine the level of
significance. RESULTS: A total of 10,379 deliveries were attended A total of 242
uterine rupture cases were included in this study. The magnitude of uterine
rupture was 2.44% (1 in 41 deliveries). Sixteen (6.6%) mothers died from uterine
rupture. Fourteen (5.8%) had experienced Vesico Vaginal Fistula. The majority of
the mothers, 72% (176), admitted for uterine rupture stayed in hospital for 6-10
days. Fetal outcome was grave, 98.3% (238) were stillborn. Place of labor
[Adjusted odds ratio (AOR): 6.92, 95% confidence interval (CI): (1.16, 33.74)],
occurrence of hypo volume shock [AOR: 3.48, 95% CI: (1.01, 11.96)] and
postoperative severe anemia [AOR: 0.092, 95% CI: (0.01, 0.956)] were
significantly associated with maternal death secondary to uterine rupture.
CONCLUSION: The magnitude of uterine rupture was high in the study area.
Initiation of labor at health institutions, early treatment of hypo-volumia and
prevention of postoperative anemia is recommended to decrease maternal death
secondary to uterine rupture.
PMID- 28403834
TI - Genome-wide comparative analysis of NBS-encoding genes in four Gossypium species.
AB - BACKGROUND: Nucleotide binding site (NBS) genes encode a large family of disease
resistance (R) proteins in plants. The availability of genomic data of the two
diploid cotton species, Gossypium arboreum and Gossypium raimondii, and the two
allotetraploid cotton species, Gossypium hirsutum (TM-1) and Gossypium barbadense
allow for a more comprehensive and systematic comparative study of NBS-encoding
genes to elucidate the mechanisms of cotton disease resistance. RESULTS: Based on
the genome assembly data, 246, 365, 588 and 682 NBS-encoding genes were
identified in G. arboreum, G. raimondii, G. hirsutum and G. barbadense,
respectively. The distribution of NBS-encoding genes among the chromosomes was
nonrandom and uneven, and was tended to form clusters. Gene structure analysis
showed that G. arboreum and G. hirsutum possessed a greater proportion of CN,
CNL, and N genes and a lower proportion of NL, TN and TNL genes compared to that
of G. raimondii and G. barbadense, while the percentages of RN and RNL genes
remained relatively unchanged. The percentage changes among them were largest for
TNL genes, about 7 times. Exon statistics showed that the average exon numbers
per NBS gene in G. raimondii and G. barbadense were all greater than that in G.
arboretum and G. hirsutum. Phylogenetic analysis revealed that the TIR-NBS genes
of G. barbadense were closely related with that of G. raimondii. Sequence
similarity analysis showed that diploid cotton G. arboreum possessed a larger
proportion of NBS-encoding genes similar to that of allotetraploid cotton G.
hirsutum, while diploid G. raimondii possessed a larger proportion of NBS
encoding genes similar to that of allotetraploid cotton G. barbadense. The
synteny analysis showed that more NBS genes in G. raimondii and G. arboreum were
syntenic with that in G. barbadense and G. hirsutum, respectively. CONCLUSIONS:
The structural architectures, amino acid sequence similarities and synteny of NBS
encoding genes between G. arboreum and G. hirsutum, and between G. raimondii and
G. barbadense were the highest among comparisons between the diploid and
allotetraploid genomes, indicating that G. hirsutum inherited more NBS-encoding
genes from G. arboreum, while G. barbadense inherited more NBS-encoding genes
from G. raimondii. This asymmetric evolution of NBS-encoding genes may help to
explain why G. raimondii and G. barbadense are more resistant to Verticillium
wilt, whereas G. arboreum and G. hirsutum are more susceptible to Verticillium
wilt. The disease resistances of the allotetraploid cotton were related to their
NBS-encoding genes especially in regard from which diploid progenitor they were
derived, and the TNL genes may have a significant role in disease resistance to
Verticillium wilt in G. raimondii and G. barbadense.
PMID- 28403835
TI - Bacteremia caused by Bergeyella zoohelcum in an infective endocarditis patient:
case report and review of literature.
AB - BACKGROUND: Bergeyella zoohelcum is an aerobic, Gram-negative bacterium that is
frequently isolated from the upper respiratory tract of dogs, cats and other
mammals. Clinically, B. zoohelcum has been reported causing cellulitis,
tenosynovitis, leg abscess and septicemia, which is closely connected with animal
bites. Here we describe a case of bacteremia in an infective endocarditis (IE)
patient caused by B. zoohelcum, in China. CASE PRESENTATION: A 27-year-old
infective endocarditis woman who had no history of dog bite nor other mammal
exposure suffered bacteremia caused by B. zoohelcum. This patient, without
evidence of polymicrobial infection, was treated with cefuroxime and had a good
outcome. CONCLUSIONS: B. zoolhelcum bacteremia is rarely reported in IE patients.
Our report expands the range of known bacterial causes of infective endocarditis.
PMID- 28403836
TI - An adaptive threshold determination method of feature screening for genomic
selection.
AB - BACKGROUND: Although the dimension of the entire genome can be extremely large,
only a parsimonious set of influential SNPs are correlated with a particular
complex trait and are important to the prediction of the trait. Efficiently and
accurately selecting these influential SNPs from millions of candidates is in
high demand, but poses challenges. We propose a backward elimination iterative
distance correlation (BE-IDC) procedure to select the smallest subset of SNPs
that guarantees sufficient prediction accuracy, while also solving the unclear
threshold issue for traditional feature screening approaches. RESULTS: Verified
through six simulations, the adaptive threshold estimated by the BE-IDC performed
uniformly better than fixed threshold methods that have been used in the current
literature. We also applied BE-IDC to an Arabidopsis thaliana genome-wide data.
Out of 216,130 SNPs, BE-IDC selected four influential SNPs, and confirmed the
same FRIGIDA gene that was reported by two other traditional methods.
CONCLUSIONS: BE-IDC accommodates both the prediction accuracy and the
computational speed that are highly demanded in the genomic selection.
PMID- 28403837
TI - Effect of individualized communication skills training on physicians' discussion
of clinical trials in oncology: results from a randomized controlled trial.
AB - BACKGROUND: Discussing randomized clinical trials (RCTs) with cancer patients is
one of the most challenging communication tasks a physician faces. Only two prior
Communication Skills Trainings (CSTs) focused on RCTs in oncology have been
reported. Their results demonstrated the need for further improvement. We
developed and evaluated an enhanced, individually-tailored CST focused on
improving physicians' communication during discussions of RCTs. METHODS: The CST
focused on personal learning goals derived from video pre-assessment that were
addressed in a 1.5-day group workshop and one-on-one coaching sessions. Forty
physicians were recruited and randomly assigned to intervention and control
groups. Video-recorded standardized consultations with actor-patients were
utilized. As a primary outcome (1), training success was evaluated by blinded
raters using a previously developed checklist. Change in checklist items was
evaluated between pre- and post-training assessment and compared against control
group results. As a secondary outcome (2), the physicians' feeling of confidence
was assessed by a questionnaire. RESULTS: (1) Significant improvements in the
intervention group were observed for the score on all items (p = 0.03), for the
subgroup of content-specific items (p = 0.02), and for the global rating of
communication competence (p = 0.04). The improvement observed for the subgroup of
general communication skill items did not achieve significance (p = 0.20). (2)
The feeling of confidence improved in nine out of ten domains. CONCLUSION: While
the individually-tailored CST program significantly improved the physicians'
discussions of RCTs, specifically related to discussion content, what remains
unknown is the influence of such programs in practice on participant recruitment
rates. The study was registered retrospectively in 2010/07/22 under DRKS-ID:
DRKS00000492 .
PMID- 28403838
TI - A Dalbergia odorifera extract improves the survival of endotoxemia model mice by
inhibiting HMGB1 release.
AB - BACKGROUND: Dalbergia odorifera T. Chen (Leguminosae) is an indigenous medicinal
herb that is widely used as a popular remedy in northern and eastern Asia.
However, the cellular mechanisms underlying the biological activity of D.
odorifera are not fully elucidated. METHODS: Anti-inflammatory effect of D.
odorifera extract (DOE) was determined through intraperitoneal injection in a
mouse model of endotoxemia induced by lipopolysaccharide (LPS). RAW 264.7 cells,
a murine macrophage, were also treated with LPS to generate a cellular model of
inflammation, and investigated the anti-inflammatory activity and underlying
mechanisms of DOE and its constituent isoliquiritigenin. RESULTS: DOE dose
dependently inhibited LPS-induced release of high mobility group box 1 (HMGB1), a
late proinflammatory cytokine, and decreased cytosolic translocation of HMGB1 in
RAW264.7 cells. This inhibitory effect of DOE on HMGB1 release was observed in
cells treated with DOE before or after LPS treatment, suggesting that DOE is
effective for both treatment and prevention. In addition, DOE significantly
inhibited LPS-induced formation of nitric oxide (NO) and expression of inducible
NO synthase (iNOS) in a dose-dependent manner. These effects of DOE were
accompanied by suppression of HMGB1 release triggered by LPS, suggesting a
possible mechanism by which DOE modulates HMGB1 release through NO signaling.
Isoriquiritigenin, a constituent of DOE, also attenuated LPS-triggered NO
formation and HMGB1 release in RAW264.7 cells, indicating that isoriquiritigenin
is an indexing molecule for the anti-inflammatory properties of DOE. Furthermore,
c-Jun N-terminal kinase, but not extracellular signal-regulated kinase and p38,
mediated DOE-dependent inhibition of HMGB1 release and NO/iNOS induction in RAW
264.7 cells exposed to LPS. Notably, administration of DOE ameliorated survival
rates in a mouse model of endotoxemia induced by LPS, where decreased level of
circulating HMGB1 was observed. CONCLUSION: These results suggest that DOE
confers resistance to LPS-triggered inflammation through NO-mediated inhibitory
effects on HMGB1 release.
PMID- 28403839
TI - Transfer between hospitals as a predictor of delay in diagnosis and treatment of
patients with Non-Small Cell Lung Cancer - a register based cohort-study.
AB - BACKGROUND: Lung cancer is the second most frequent cancer diagnosis in Denmark.
Although improved during the last decade, the prognosis of lung cancer is still
poor with an overall 5-year survival rate of approximately 12%. Delay in
diagnosis and treatment of lung cancer has been suggested as a potential cause of
the poor prognosis and as consequence, fast track cancer care pathways were
implemented describing maximum acceptable time thresholds from referral to
treatment. In Denmark, patients with lung cancer are often transferred between
hospitals with diagnostic facilities to hospitals with treatment facilities
during the care pathway. We wanted to investigate whether this organizational set
up influenced the time that patients wait for the diagnosis and treatment.
Therefore, the objective of this study was to uncover the impact of transfer
between hospitals on the delay in the diagnosis and treatment of Non-Small Cell
Lung Cancer (NSCLC). METHODS: We performed a historical prospective cohort study
using data from the Danish Lung Cancer Registry (DLCR). All patients diagnosed
with primary NSCLC from January 1st 2008 to December 31st 2012 were included.
Patients with unresolved pathology and incomplete data on the dates of referral,
diagnosis and treatment were excluded. RESULTS: A total of 11 273 patients were
included for further analyses. Transfer patients waited longer for treatment
after the diagnosis, (Hazard ratio (HR) 0.81 (0.68-0.96)) and in total time from
referral to treatment (HR 0.84 (0.77-0.92)), than no-transfer patients. Transfer
patients had lower odds of being diagnosed (Odds Ratio (OR) 0.82 (0.74-0.94) and
treated (OR 0.66 (0.61-0.72) within the acceptable time thresholds described in
the care pathway. CONCLUSION: Fast track cancer care pathways were implemented to
unify and accelerate the diagnosis and treatment of cancer. We found that the
transfer between hospitals during the care pathway might cause delay from
diagnosis to treatment as well as in the total time from referral to treatment in
patients with Non Small-Cell Lung Cancer. The difference between no-transfer and
transfer patients persists after adjusting for known predictors of delay.
PMID- 28403840
TI - Variation in fat content between liver lobes and comparison with
histopathological scores in dairy cows with fatty liver.
AB - BACKGROUND: The assessment of a liver biopsy remains the gold standard for
diagnosing and staging fatty liver in dairy cows, which is often necessary for
diagnostic and research purposes. Accuracy of the diagnosis relays on the quality
of the biopsy, the assumed representativeness of a small tissue sample for a
disease process throughout the liver and accurate human evaluation of histologic
specimens. The objective of the present study was to assess the distribution of
triacylglycerol (TAG) infiltration throughout the parenchyma of livers with
different degrees of fatty liver in dairy cows. In addition, histopathological
scores from the corresponding specimens were compared to a quantitative
measurement of TAG, as well as the agreement between two observers. METHODS:
Thirty livers with different degrees of lipid infiltration were selected and 10
different locations throughout the liver were assessed. The TAG content was
measured enzymatically, calculated in % or mg/g wet weight, and assigned to a
scoring system. Corresponding tissue specimens were stained with hematoxylin
eosin (H&E) and Oil red O (ORO) for histopathological evaluation, using a scoring
system. RESULTS: The difference in TAG content between any locations was less
than 2%. Based on the scoring system the TAG concentration was even distributed
in 79.3% of the livers. Based on kappa statistics the agreement between two
pathologists and staining technique in scoring histological specimens was
moderate to fair. CONCLUSIONS: Overall the distribution of TAG throughout the
liver and the accuracy of human evaluation of liver biopsies may lead to
acceptable diagnoses for clinical purposes. Within the liver lobules a common
pattern of lipid distribution depending on severity could be observed. For the
staging of lipid infiltration for research projects, some degree of variation
needs to be considered.
PMID- 28403841
TI - A systematic review and meta-analysis of trypanosome prevalence in tsetse flies.
AB - BACKGROUND: The optimisation of trypanosomosis control programs warrants a good
knowledge of the main vector of animal and human trypanosomes in sub-Saharan
Africa, the tsetse fly. An important aspect of the tsetse fly population is its
trypanosome infection prevalence, as it determines the intensity of the
transmission of the parasite by the vector. We therefore conducted a systematic
review of published studies documenting trypanosome infection prevalence from
field surveys or from laboratory experiments under controlled conditions.
Publications were screened in the Web of Science, PubMed and Google Scholar
databases. Using the four-stage (identification, screening, eligibility and
inclusion) process in the PRISMA statement the initial screened total of 605
studies were reduced to 72 studies. The microscopic examination of dissected
flies (dissection method) remains the most used method to detect trypanosomes and
thus constituted the main focus of this analysis. Meta-regression was performed
to identify factors responsible for high trypanosome prevalence in the vectors
and a random effects meta-analysis was used to report the sensitivity of
molecular and serological tests using the dissection method as gold standard.
RESULTS: The overall pooled prevalence was 10.3% (95% confidence interval [CI] =
8.1%, 12.4%) and 31.0% (95% CI = 20.0%, 42.0%) for the field survey and
laboratory experiment data respectively. The country and the year of publication
were found to be significantly factors associated with the prevalence of
trypanosome infection in tsetse flies. The alternative diagnostic tools applied
to dissection positive samples were characterised by low sensitivity, and no
information on the specificity was available at all. CONCLUSION: Both temporal
and spatial variation in trypanosome infection prevalence of field collected
tsetse flies exists, but further investigation on real risk factors is needed how
this variation can be explained. Improving the sensitivity and determining the
specificity of these alternative diagnostic tools should be a priority and will
allow to estimate the prevalence of trypanosome infection in tsetse flies in high
throughput.
PMID- 28403843
TI - Knowledge about preventive dentistry versus self-reported competence in providing
preventive oral healthcare - a study among Nepalese dentists.
AB - BACKGROUND: Dentists' and dental healthcare providers' professional knowledge and
attitude towards the prevention of oral diseases may have an impact on the oral
health of the general population. The aim of this study was to describe Nepalese
dentists' competency in giving preventive education and treatment to their
patients, and to assess their level of knowledge about preventive dental health.
METHODS: This was a cross-sectional study of 195 dentists (71 males and 124
females). Knowledge of preventive oral healthcare and self-reported aspects of
preventive oral healthcare were assessed using a close-ended multiple-choice
questionnaire. Statistical evaluation was done using chi-squared test,
independent sample t-test and factor analysis as appropriate. RESULTS: More than
90% of dentists self-reported to be competent in providing preventive treatment
and oral hygiene education to their patients. Female dentists reported being more
competent in giving oral hygiene education than their male counterparts (p =
0.045). Dentists scored a mean of 24.06 +/- 3.8 [range (15-33)] out of 56 on
knowledge based on self-reported awareness of seven different aspects of
preventive dentistry. More than 70% of the dentists had relatively good knowledge
regarding the use of fluoride, whereas the preventive knowledge in other aspects
of dental health such as frequency of sugar consumption, xylitol use, dental
visits, sealant, gingival health, dental and general health was found to be
limited. CONCLUSIONS: The majority of participating dentists reported a high
level of general competency in providing preventive treatment and oral health
education to their patients, whereas their knowledge was found to be limited in
some aspects of preventive dentistry.
PMID- 28403842
TI - Outcomes of autologous bone marrow mononuclear cells for cerebral palsy: an open
label uncontrolled clinical trial.
AB - BACKGROUND: Stem cell therapy has emerged as a promising method for improving
motor function of patients with cerebral palsy. The aim of this study is to
assess the safety and effectiveness of autologous bone marrow mononuclear stem
cell transplantation in patients with cerebral palsy related to oxygen
deprivation. METHODS: An open label uncontrolled clinical trial was carried out
at Vinmec International Hospital. The intervention consisted of two
administrations of stem cells, the first at baseline and the second 3 months
later. Improvement was monitored at 3 months and 6 months after the first
administration of stem cells, using the Gross Motor Function Measure (GMFM) and
Modified Ashworth Score which measures muscle tone. RESULTS: No severe
complications were recorded during the study. After transplantation, 12 patients
encountered fever without infections and 9 patients experienced vomiting which
was easily managed with medications. Gross motor function was markedly improved 3
months or 6 months after stem cell transplantation than at baseline. The post
transplantation GMFM-88 total score, each of its domains and the GMFM-66
percentile were all significantly higher (p-value < 0.001). Muscle spasticity
also reduced significantly after transplantation (p-value < 0.001). The therapy
was equally effective regardless of sex, age and GMFCS level (p-value > 0.05).
CONCLUSION: Autologous bone marrow mononuclear cell transplantation appears to be
a safe and effective therapy for patients with cerebral palsy. TRIAL
REGISTRATION: ClinicalTrials.gov Identifier: NCT02569775 . Retrospectively
registered on October 15, 2015.
PMID- 28403844
TI - Health and legal literacy for migrants: twinned strands woven in the cloth of
social justice and the human right to health care.
AB - BACKGROUND: Based on an analysis of published literature, this paper provides an
over-view of the challenges associated with delivering on the right to access
quality health care for international migrants to industrialized countries, and
asks which group of professionals is best equipped to provide services that
increase health and legal literacy. Both rights and challenges are approached
from a social justice perspective with the aim of identifying opportunities to
promote greater health equity. That is, to go beyond the legal dictates enshrined
in principles of equality, and target as an ethical imperative a situation where
all migrants receive the particular assistance they need to overcome the barriers
that inhibit their equitable access to health care. This assistance is especially
important for migrant groups that are further disadvantaged by differing cultural
constructions of gender. Viewing the topic from this perspective makes evident a
gap in both research literature and policy. The review has found that while
health literacy is debated and enshrined as a policy objective, and consideration
is given to improving legal literacy as a means of challenging social injustice
in developing nations, however, no discussion has been identified that considers
assisting migrants to gain legal literacy as a step toward achieving not only
health literacy and improved health outcomes, but critical participation as
members of their adoptive society. CONCLUSION: Increasing migrant health
literacy, amalgamated with legal literacy, aids migrants to better access their
human right to appropriate care, which in turn demonstrably assists in increasing
social engagement, citizenship and productivity. However what is not evident in
the literature, is which bureaucratic or societal group holds responsibility for
assisting migrants to develop critical citizenship literacy skills. This paper
proposes that a debate is required to determine both who is best placed to
provide services that increase health and legal literacy, and how they should be
resourced, trained and equipped.
PMID- 28403845
TI - Hemosiderin in sputum macrophages may predict infective exacerbations of chronic
obstructive pulmonary disease: a retrospective observational study.
AB - BACKGROUND: Infective exacerbations of COPD are common and are accompanied by
neutrophilic bronchitis in sputum. Increased respiratory iron content has been
associated with respiratory tract infection, though it is unclear if this
represents a predisposing factor for infection or the sequelae of inflammation.
Iron overload, as assessed in the airways, may be an important biomarker for
recurrent infective exacerbations of COPD. The purpose of our study was to
determine if hemosiderin in sputum macrophages is related to infective
exacerbations of COPD. METHODS: We undertook a retrospective observational study
of 54 consecutive patients who presented with an exacerbation of COPD and had
sputum examined including assessment for hemosiderin in alveolar macrophages. The
relation between infective exacerbations in the previous two years and the
percent of hemosiderin-positive macrophages was analyzed with linear regression.
To account for the non-parametric distribution of infective exacerbations,
negative binomial regression modelling was used to account for other covariates.
RESULTS: The percent of hemosiderin positive alveolar macrophages (hemosiderin
index), analyzed parametrically and non-parametrically, demonstrated a
significant correlation with increasing numbers of infective exacerbations in the
previous two years. In a multivariate regression analysis, hemosiderin index was
an independent predictor of infective exacerbations. COPD patients with raised
hemosiderin index (>=20%) had higher levels of sputum IL-6 compared to patients
with lower levels (<20%). CONCLUSIONS: High hemosiderin index in sputum alveolar
macrophages measured at the time of AECOPD may be related to the frequency of
infective exacerbations of COPD.
PMID- 28403846
TI - The new field of 'precision psychiatry'.
AB - BACKGROUND: Precision medicine is a new and important topic in psychiatry.
Psychiatry has not yet benefited from the advanced diagnostic and therapeutic
technologies that form an integral part of other clinical specialties. Thus, the
vision of precision medicine as applied to psychiatry - 'precision psychiatry' -
promises to be even more transformative than in other fields of medicine, which
have already lessened the translational gap. DISCUSSION: Herein, we describe
'precision psychiatry' and how its several implications promise to transform the
psychiatric landscape. We pay particular attention to biomarkers and to how the
development of new technologies now makes their discovery possible and timely.
The adoption of the term 'precision psychiatry' will help propel the field, since
the current term 'precision medicine', as applied to psychiatry, is impractical
and does not appropriately distinguish the field. Naming the field 'precision
psychiatry' will help establish a stronger, unique identity to what promises to
be the most important area in psychiatry in years to come. CONCLUSION: In
summary, we provide a wide-angle lens overview of what this new field is, suggest
how to propel the field forward, and provide a vision of the near future, with
'precision psychiatry' representing a paradigm shift that promises to change the
landscape of how psychiatry is currently conceived.
PMID- 28403847
TI - Erratum to: Brain structure differences among male schizophrenic patients with
history of serious violent acts: an MRI voxel-based morphometric study.
PMID- 28403848
TI - Laparoscopic treatment of abdominal unicentric castleman's disease: a case report
and literature review.
AB - BACKGROUND: Castleman's disease is a rare lymphoproliferative disorder of unknown
etiology that most commonly presents as a mediastinal nodal mass. It is
exceptionally uncommon for Castleman's disease to present in the mesentery and,
only 53 cases have ever been described in the literature. Standard treatment for
this lymphoproliferative disorder involving a single node is a complete "en bloc"
surgical resection which has proven to be a curative approach in almost all cases
without recurrence after 20 years of follow up. All 53 reported cases of
mesenteric Castleman's disease, except one, were treated with laparotomy. CASE
PRESENTATION: We report on a case of mesenteric Castleman's disease localized in
the mesentery which is the second reported case if its kind and was treated by a
laparoscopic-assisted procedure. Our female patient had an uneventful
postoperative course and was discharged in the 5th post-operative day. No signs
of recurrence were present as evidenced by physical examination and total body CT
scan 24 months after the operation. We compare our case with the other reported
cases in which Castleman's disease presented as an isolated mass in the abdomen.
CONCLUSION: Although a rare disease, Unicentric Castleman's disease should always
be considered when a solid asymptomatic abdominal mass is occasionally presented.
The laparoscopic approach (LA) allows for the achievement of better results than
open surgery, including a reduction in postoperative pain and length of hospital
stay. In cases of masses of an uncertain nature, LA must be considered the last
diagnostic tool and the first treatment one.
PMID- 28403849
TI - Real life persistence rate with antimuscarinic treatment in patients with
idiopathic or neurogenic overactive bladder: a prospective cohort study with
solifenacin.
AB - BACKGROUND: Several studies have shown that the antimuscarinic treatment of
overactive bladder is characterized by low long-term persistence rates. We have
investigated the persistence of solifenacin in real life by means of telephonic
interviews in a prospective cohort. We included both patients with idiopathic
overactive bladder as well as neurogenic overactive bladder. METHODS: From June
2009 until July 2012 patients with idiopathic or neurogenic overactive bladder
who were newly prescribed solifenacin were included. In total 123 subjects were
followed prospectively during one year by means of four telephonic interviews,
which included questions about medication use and adverse events. RESULTS: After
one year 40% of all patients included was still using solifenacin, 50%
discontinued and 10% was lost to follow-up. In the neurogenic group 58% was still
using solifenacin versus 32% in the idiopathic group after one year (p < 0,05).
The main reasons to stop solifenacin were lack of efficacy, side effects and a
combination of both. CONCLUSIONS: This prospective cohort study showed a real
life continuation rate of 40% after 12 months. This continuation rate is higher
than found in most other studies. The use of regular telephonic evaluation might
have improved medication persistence. The findings of this study also suggest
that patients with neurogenic overactive bladder have a better persistence with
this method of evaluation compared to patients with idiopathic overactive
bladder. TRIAL REGISTRATION: This study was retrospectively registered on march
17, 2017 at the ISRCTN registry with study ID ISRCTN13129226 .
PMID- 28403851
TI - Making connections across silos: intimate partner violence, mental health, and
substance use.
AB - BACKGROUND: Untold numbers of women worldwide are survivors of intimate partner
violence (IPV) with a substantial number of these experiencing co-occurring
mental health and substance use problems. Despite the complex interconnections
among these problems, funding mechanisms and organizational structures and
mandates have been designed to address just a single, focal problem. One of the
challenges for frontline providers is the lack of effective, evidence-informed
inter-professional education or training to help them identify and appropriately
respond to co-occurring problems. We developed an evidence-informed, competency
based curriculum to address this gap. In this paper we report on its
effectiveness in increasing knowledge, changing beliefs and enhancing skills of
frontline workers from all three sectors. METHODS: The curriculum consists of
multiple elements: a text manual; an interactive, online series of modules; and,
an in-person workshop. Frontline workers (n = 1111) in the violence against women
(VAW) (n = 499), mental health (n = 229), addiction treatment (n = 167), and
associated sectors (n = 149) were recruited to attend the workshop and instructed
to read the manual or complete the online modules before attending. Some failed
to respond (n = 67). Online pre- and post-tests were used to assess changes in
knowledge, beliefs and skills; evaluations of the workshop were also collected.
RESULTS: Matched pre- and post-tests were available for over half of the
participants (n = 624). Results show statistically significant improvements
across all six competency domains from pre to post-test (p <0.0001). Significant
changes in participants' knowledge and stigmatizing beliefs were achieved. There
was no correlation among differences in sector, age, size of organization, years
of experience or prior training. Participant feedback made evident prior
misconceptions about women experiencing co-occurring problems, improved
understanding about the need to bridge silos, as well as the need for enhanced
self-care. CONCLUSIONS: An educational intervention designed to sensitize
frontline workers to the realities of women's experiences of co-occurring
problems, educate about the challenges of accessing help when there are co
occurring problems, and bridge discipline and practice-based silos, can
effectively challenge and alter providers' negative attitudes and stigmatizing
beliefs. Decreasing stigmatizing beliefs and increasing knowledge has the
potential to help survivors access needed help.
PMID- 28403850
TI - Rationale and design of a multicenter placebo-controlled double-blind randomized
trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM
trial.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by systemic
metabolic abnormalities and the development of micro- and macrovascular
complications, resulting in a shortened life expectancy. A recent cardiovascular
(CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a
sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and
all-cause mortality and hospitalization for heart failure in patients with T2DM
and established CV disease (CVD). SGLT2 inhibitors are known to not only decrease
plasma glucose levels, but also favorably modulate a wide range of metabolic and
hemodynamic disorders related to CV pathways. Although some experimental studies
revealed a beneficial effect of SGLT2 inhibitors on atherosclerosis, there is a
paucity of clinical data showing that they can slow the progression of
atherosclerosis in patients with T2DM. Therefore, the EMBLEM trial was designed
to investigate whether empagliflozin treatment can improve endothelial function,
which plays a pivotal role in the pathogenesis of atherosclerosis, in patients
with T2DM and established CVD. METHODS: The EMBLEM trial is an ongoing,
prospective, multicenter, placebo-controlled double-blind randomized,
investigator-initiated clinical trial in Japan. A total of 110 participants with
T2DM (HbA1c range 6.0-10.0%) and with established CVD will be randomized (1:1) to
receive either empagliflozin 10 mg once daily or a placebo. The primary endpoint
of the trial is change in the reactive hyperemia (RH)-peripheral arterial
tonometry-derived RH index at 24 weeks from baseline. For comparison of treatment
effects between the treatment groups, the baseline-adjusted means and their 95%
confidence intervals will be estimated by analysis of covariance adjusted for the
following allocation factors: HbA1c (<7.0 or >=7.0%), age (<65 or >=65 years),
systolic blood pressure (<140 or >=140 mmHg), and current smoking status
(nonsmoker or smoker). Key secondary endpoints include the change from baseline
for other vascular-related markers such as arterial stiffness, sympathetic
nervous activity, and parameters of cardiac and renal function. Importantly,
serious adverse effects independently on the causal relationship to the trial
drugs and protocol will be also evaluated throughout the trial period.
DISCUSSION: EMBLEM is the first trial to assess the effect of empagliflozin on
endothelial function in patients with T2DM and established CVD. Additionally,
mechanisms associating empagliflozin-mediated actions with endothelial function
and other CV markers will be evaluated. Thus, the trial is designed to elucidate
potential mechanisms by which empagliflozin protects CV systems and improves CV
outcomes. Trial registration Unique Trial Number, UMIN000024502 (
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028197 ).
PMID- 28403852
TI - Health workers perceptions and attitude about Ghana's preparedness towards
preventing, containing, and managing Ebola Virus Disease.
AB - BACKGROUND: Ebola virus is highly infectious and the disease can be very fatal.
The World Health Organization has declared the 2014-2015 Ebola Virus Disease
outbreak a Public Health Emergency of International Concern. In response to this,
preparations were made in various health facilities and entry points across
Ghana. This study explored health workers perceptions, and attitude about Ghana's
preparedness towards preventing and containing Ebola Virus Disease. METHODS: We
conducted a qualitative study in five (5) of the ten (10) regions in Ghana. Five
focus group discussions (N = 44) were conducted among nurses; one in each region.
In addition, ten (10) health workers (2 in each region) who are members of
regional Ebola Virus Disease task force were recruited and interviewed. In the
Greater Accra, Volta and Western regions that have ports, six (6) port health
officials: two in each of these regions were also interviewed. The interviews
were recorded digitally and transcribed verbatim. Thematic content analysis was
used to analyze the transcripts with the aid of NVivo 10 software. RESULTS: The
results of this study showed that Ghanaian health workers perceived the screening
at various ports as important and ongoing but felt that the screenings at in-land
ports were being undermined by the use of unapproved routes. Training of health
workers was also being carried out in all the regions, however, there was a
general perception among 33 out of 44 nurses that majority of health workers have
not received training on Ebola Virus Disease prevention and management.
Logistical challenges were also reported as some health facilities did not have
adequate Personal Protective Equipment. In facilities where equipment was
available, they were stored in places which are not easily accessible to health
workers at all times of the day. Human resource preparation was also perceived to
be a challenge as health workers (38/44 of nurses) generally expressed fear and
unwillingness to work in Ebola treatment centres in the event of an outbreak in
Ghana. CONCLUSIONS: Our study concludes that preparatory work for Ebola Virus
Disease prevention and containment in Ghana is perceived as inadequate by health
workers. Ghana needs to strengthen preparation in the area of training of health
workers, provision and accessibility of Personal Protective Equipment and
incentives for health workers to better position her to contain and manage any
Ebola Virus Disease outbreak.
PMID- 28403853
TI - The application of DEA (Data Envelopment Analysis) window analysis in the
assessment of influence on operational efficiencies after the establishment of
branched hospitals.
AB - BACKGROUND: Many large-scaled public hospitals have established branched
hospitals in China. This study is to provide evidence for strategy making on the
management and development of multi-branched hospitals by evaluating and
comparing the operational efficiencies of different hospitals before and after
their establishment of branched hospitals. METHODS: DEA (Data Envelopment
Analysis) window analysis was performed on a 7-year data pool from five public
hospitals provided by health authorities and institutional surveys. RESULTS: The
operational efficiencies of sample hospitals measured in this study (including
technical efficiency, pure technical efficiency and scale efficiency) had overall
trends towards increase during this 7-year period of time, however, a temporary
downturn occurred shortly after the establishment of branched hospitals; pure
technical efficiency contributed more to the improvement of technical efficiency
compared to scale efficiency. CONCLUSIONS: The establishment of branched
hospitals did not lead to a long-term negative effect on hospital operational
efficiencies. Our data indicated the importance of improving scale efficiency via
the optimization of organizational management, as well as the advantage of a
different form of branch-establishment, merging and reorganization. This study
brought an insight into the practical application of DEA window analysis on the
assessment of hospital operational efficiencies.
PMID- 28403854
TI - Gait characterization in golden retriever muscular dystrophy dogs using linear
discriminant analysis.
AB - BACKGROUND: Accelerometric analysis of gait abnormalities in golden retriever
muscular dystrophy (GRMD) dogs is of limited sensitivity, and produces highly
complex data. The use of discriminant analysis may enable simpler and more
sensitive evaluation of treatment benefits in this important preclinical model.
METHODS: Accelerometry was performed twice monthly between the ages of 2 and 12
months on 8 healthy and 20 GRMD dogs. Seven accelerometric parameters were
analysed using linear discriminant analysis (LDA). Manipulation of the dependent
and independent variables produced three distinct models. The ability of each
model to detect gait alterations and their pattern change with age was tested
using a leave-one-out cross-validation approach. RESULTS: Selecting genotype
(healthy or GRMD) as the dependent variable resulted in a model (Model 1)
allowing a good discrimination between the gait phenotype of GRMD and healthy
dogs. However, this model was not sufficiently representative of the disease
progression. In Model 2, age in months was added as a supplementary dependent
variable (GRMD_2 to GRMD_12 and Healthy_2 to Healthy_9.5), resulting in a high
overall misclassification rate (83.2%). To improve accuracy, a third model (Model
3) was created in which age was also included as an explanatory variable. This
resulted in an overall misclassification rate lower than 12%. Model 3 was
evaluated using blinded data pertaining to 81 healthy and GRMD dogs. In all but
one case, the model correctly matched gait phenotype to the actual genotype.
Finally, we used Model 3 to reanalyse data from a previous study regarding the
effects of immunosuppressive treatments on muscular dystrophy in GRMD dogs. Our
model identified significant effect of immunosuppressive treatments on gait
quality, corroborating the original findings, with the added advantages of direct
statistical analysis with greater sensitivity and more comprehensible data
representation. CONCLUSIONS: Gait analysis using LDA allows for improved analysis
of accelerometry data by applying a decision-making analysis approach to the
evaluation of preclinical treatment benefits in GRMD dogs.
PMID- 28403855
TI - Quality of life of breast and cervical cancer survivors.
AB - BACKGROUND: Breast and cervical cancer are the most common cancers affecting
women. The symptom distresses experienced by cancer survivors are critical
factors influencing their quality of life (QOL). This study investigated the QOL
of breast and cervical cancer survivors, their physical, psychological and social
conditions. METHODS: The participants were older than 20 years, had been
diagnosed with breast or cervical cancer for more than 2 years, and had completed
their cancer treatment. The survey incorporated the QOL questionnaires developed
by the European Organization of Research and Treatment for Cancer and a self
designed questionnaire. RESULTS: The mean age at diagnosis was 48.89 +/- 8.53
years for the breast cancer survivors and 49.00 +/- 10.30 years for the cervical
cancer survivors. The corresponding QOL scores were 75.33 +/- 20.25 and 75.56 +/-
17.93. The factors influencing QOL of breast cancer survivors were household
income, number of comorbidities, stage of cancer, type of cancer treatment and
duration of illness, whereas the factor related to QOL of cervical cancer
survivors was only household income. CONCLUSIONS: The QOL of the two groups was
similar. Healthcare providers should demonstrate greater concern toward breast
and cervical cancer survivors.
PMID- 28403856
TI - Anticholangiocarcinoma activity and toxicity of the Kaempferia galanga Linn.
Rhizome ethanolic extract.
AB - BACKGROUND: Cholangiocarcinoma (CCA) is an important public health problem in
several tropical and subtropical parts of the world particularly Thailand.
Chemotherapy of CCA is largely ineffective and discovery and development of
effective alternative drugs is urgently needed. The objective of the study was to
confirm the anti-CCA potential as well as toxicity of the crude extract of
Kaempferia galangal Linn. (rhizome) both in vitro and in animal models. METHODS:
The ethanolic extract of K. galanga Linn. rhizome, ethyl-p-methoxycinnamate
(EPMC) and 5-fluorouracil (5-FU) were evaluated for their cytotoxic activities
against CCA cell line (CL-6) using MTT cell proliferation assay. Acute and
subacute toxicity of the extract were evaluated in ICR (Imprinting Control
Region) mice according to the OECD (International Organization for Economic Co
operation and Development) Guideline. Anti-CCA activity was evaluated in CCA-
xenografted nude mice. RESULTS: Results of cytotoxicity test showed moderate
activity of the extract and EPMC with median (95% confidence interval: 95% CI)
50% inhibitory concentration (IC50) of 64.2 (57.76-72.11) and 49.19 (48.16-52.29)
MUg/ml, respectively. The IC50 of 5-FU was 107.1 (103.53-109.64) MUg/ml. The
selectivity index (SI) values for the extract, EPMC and 5-FU against human normal
cell line (OUMS) and cancer cell line (CL-6) were 2.2, 2.09 and 1.31,
respectively. Toxicity testing revealed no overt toxic effect up to the maximum
single oral dose of 5000 mg/kg body weight and up to daily dose of 1000 mg/kg
body weight for 30 days. The extract at the maximum tolerated dose level of 1000
mg/kg body weight for 30 days exhibited promising anti-CCA activity in CL6
xenografted nude mice as determined by inhibitory activity on tumor growth
(58.41%) and lung metastasis (33.3%), as well as prolongation of survival time
(62 days). CONCLUSION: The K. galangal Linn. rhizome extract and its bioactive
compound EPMC exhibited moderate cytotoxic activity against human CCA tumor (CL
6) cell line. Results of toxicity testing suggest that the extract was well
tolerated up to the maximum single oral dose of 5000 mg/kg body weight and daily
dose of 1000 mg/kg body weight for 30 days. The extract exhibited promising anti
CCA activity in CL6-xenografed nude mice as determined by significant inhibitory
activity on tumor growth and lung metastasis, as well as prolongation of survival
time.
PMID- 28403857
TI - Hypermethylation of CDKN2A exon 2 in tumor, tumor-adjacent and tumor-distant
tissues from breast cancer patients.
AB - BACKGROUND: Breast carcinogenesis is a multistep process involving genetic and
epigenetic changes. Tumor tissues are frequently characterized by gene-specific
hypermethylation and global DNA hypomethylation. Aberrant DNA methylation levels
have, however, not only been found in tumors, but also in tumor-surrounding
tissue appearing histologically normal. This phenomenon is called field
cancerization. Knowledge of the existence of a cancer field and its spread are of
clinical relevance. If the tissue showing pre-neoplastic lesions is not removed
by surgery, it may develop into invasive carcinoma. METHODS: We investigated the
prevalence of gene-specific and global DNA methylation changes in tumor-adjacent
and tumor-distant tissues in comparison to tumor tissues from the same breast
cancer patients (n = 18) and normal breast tissues from healthy women (n = 4).
Methylation-sensitive high resolution melting (MS-HRM) analysis was applied to
determine methylation levels in the promoters of APC, BRCA1, CDKN2A (p16), ESR1,
HER2/neu and PTEN, in CDKN2A exon 2 and in LINE-1, as indicator for the global
DNA methylation extent. The methylation status of the ESR2 promoter was
determined by pyrosequencing. RESULTS: Tumor-adjacent and tumor-distant tissues
frequently showed pre-neoplastic gene-specific and global DNA methylation
changes. The APC promoter (p = 0.003) and exon 2 of CDKN2A (p < 0.001) were
significantly higher methylated in tumors than in normal breast tissues from
healthy women. For both regions, significant differences were also found between
tumor and tumor-adjacent tissues (p = 0.001 and p < 0.001, respectively) and
tumor and tumor-distant tissues (p = 0.001 and p < 0.001, respectively) from
breast cancer patients. In addition, tumor-adjacent (p = 0.002) and tumor-distant
tissues (p = 0.005) showed significantly higher methylation levels of CDKN2A exon
2 than normal breast tissues serving as control. Significant correlations were
found between the proliferative activity and the methylation status of CDKN2A
exon 2 in tumor (r = -0.485, p = 0.041) and tumor-distant tissues (r = -0.498, p
= 0.036). CONCLUSIONS: From our results we can conclude that methylation changes
in CDKN2A exon 2 are associated with breast carcinogenesis. Further
investigations are, however, necessary to confirm that hypermethylation of CDKN2A
exon 2 is associated with tumor proliferative activity.
PMID- 28403858
TI - Contraceptive service provider imposed restrictions to contraceptive access in
urban Nigeria.
AB - BACKGROUND: Health service providers can restrict access to contraceptives
through their own imposed biases about method appropriateness. In this study,
provider biases toward contraceptive service provision among urban Nigerian
providers was assessed. METHODS: Health providers working in health facilities,
as well as pharmacists and patent medical vendors (PMV), in Abuja, Benin City,
Ibadan, Ilorin, Kaduna, and Zaria, were surveyed in 2011 concerning their self
reported biases in service provision based on age, parity, and marital status.
RESULTS: Minimum age bias was the most common bias while minimum parity was the
least common bias reported by providers. Condoms were consistently provided with
the least amount of bias, followed by provision of emergency contraception (EC),
pills, injectables, and IUDs. Experience of in-service training for health
facility providers was associated with decreased prevalence of marital status
bias for the pill, injectable, and IUD; however, training experience did not, or
had the opposite effect on, pharmacists and PMV operator's reports of service
provision bias. CONCLUSIONS: Provider imposed eligibility barriers in urban study
sites in Nigeria were pervasive - the most prevalent restriction across method
and provider type was minimum age. Given the large and growing adolescent
population - interventions aimed at increasing supportive provision of
contraceptives to youth in this context are urgently needed. The results show
that the effect of in-service training on provider biases was limited. Future
efforts to address provider biases in contraceptive service provision, among all
provider types, must find creative ways to address this critical barrier to
increased contraceptive use.
PMID- 28403859
TI - Managing uncertainty - a qualitative study of surgeons' decision-making for one
stage and two-stage revision surgery for prosthetic hip joint infection.
AB - BACKGROUND: Approximately 88,000 primary hip replacements are performed in
England and Wales each year. Around 1% go on to develop deep prosthetic joint
infection. Between one-stage and two-stage revision arthroplasty best treatment
options remain unclear. Our aims were to characterise consultant orthopaedic
surgeons' decisions about performing either one-stage or two-stage revision
surgery for patients with deep prosthetic infection (PJI) after hip arthroplasty,
and to identify whether a randomised trial comparing one-stage with two-stage
revision would be feasible. METHODS: Semi-structured interviews were conducted
with 12 consultant surgeons who perform revision surgery for PJI after hip
arthroplasty at 5 high-volume National Health Service (NHS) orthopaedic
departments in England and Wales. Surgeons were interviewed before the
development of a multicentre randomised controlled trial. Data were analysed
using a thematic approach. RESULTS: There is no single standardised surgical
intervention for the treatment of PJI. Surgeons balance multiple factors when
choosing a surgical strategy which include multiple patient-related factors,
their own knowledge and expertise, available infrastructure and the infecting
organism. Surgeons questioned whether it was appropriate that the two-stage
revision remained the best treatment, and some surgeons' willingness to consider
more one-stage revisions had increased over recent years and were influenced by
growing evidence showing equivalence between surgical techniques, and local
observations of successful one-stage revisions. Custom-made articulating spacers
was a practice that enabled uncertainty to be managed in the absence of
definitive evidence about the superiority of one surgical technique over the
other. Surgeons highlighted the need for research evidence to inform practice and
thought that a randomised trial to compare treatments was needed. Most surgeons
thought that patients who they treated would be eligible for trial participation
in instances where there was uncertainty about the best treatment option.
CONCLUSIONS: Surgeons highlighted the need for evidence to support their choice
of revision. Some surgeons' willingness to consider one-stage revision for
infection had increased over time, largely influenced by evidence of successful
one-stage revisions. Custom-made articulating spacers also enabled surgeons to
manage uncertainty about the superiority of surgical techniques. Surgeons thought
that a prospective randomised controlled trial comparing one-stage with two-stage
joint replacement is needed and that randomisation would be feasible.
PMID- 28403860
TI - The social accountability of doctors: a relationship based framework for
understanding emergent community concepts of caring.
AB - BACKGROUND: Social accountability is defined as the responsibility of
institutions to respond to the health priorities of a community. There is an
international movement towards the education of health professionals who are
accountable to communities. There is little evidence of how communities
experience or articulate this accountability. METHODS: In this grounded theory
study eight community based focus group discussions were conducted in rural and
urban South Africa to explore community members' perceptions of the social
accountability of doctors. The discussions were conducted across one urban and
two rural provinces. Group discussions were recorded and transcribed verbatim.
RESULTS: Initial coding was done and three main themes emerged following data
analysis: the consultation as a place of love and respect (participants have an
expectation of care yet are often engaged with disregard); relationships of
people and systems (participants reflect on their health priorities and the links
with the social determinants of health) and Ubuntu as engagement of the community
(reflected in their expectation of Ubuntu based relationships as well as part of
the education system). These themes were related through a framework which
integrates three levels of relationship: a central community of reciprocal
relationships with the doctor-patient relationship as core; a level in which the
systems of health and education interact and together with social determinants of
health mediate the insertion of communities into a broader discourse. An ubuntu
framing in which the tensions between vulnerability and power interact and
reflect rights and responsibility. The space between these concepts is important
for social accountability. CONCLUSION: Social accountability has been a concept
better articulated by academics and centralized agencies. Communities bring a
richer dimension to social accountability through their understanding of being
human and caring. This study also creates the connection between ubuntu and
social accountability and their mutual transformative capacity as agents for
social justice.
PMID- 28403861
TI - Cardiac shock-wave therapy in the treatment of coronary artery disease:
systematic review and meta-analysis.
AB - AIM: To systematically review currently available cardiac shock-wave therapy
(CSWT) studies in humans and perform meta-analysis regarding anti-anginal
efficacy of CSWT. METHODS: The Cochrane Controlled Trials Register, Medline,
Medscape, Research Gate, Science Direct, and Web of Science databases were
explored. In total 39 studies evaluating the efficacy of CSWT in patients with
stable angina were identified including single arm, non- and randomized trials.
Information on study design, subject's characteristics, clinical data and
endpoints were obtained. Assessment of publication risk of bias was performed and
heterogeneity across the studies was calculated by using random effects model.
RESULTS: Totally, 1189 patients were included in 39 reviewed studies, with 1006
patients treated with CSWT. The largest patient sample of single arm study
consisted of 111 patients. All selected studies demonstrated significant
improvement in subjective measures of angina symptoms and/or quality of life, in
the majority of studies left ventricular function and myocardial perfusion
improved. In 12 controlled studies with 483 patients included (183 controls)
angina class, Seattle Angina Questionnaire (SAQ) score, nitrates consumption were
significantly improved after the treatment. In 593 participants across 22 studies
the exercise capacity was significantly improved after CSWT, as compared with the
baseline values (in meta-analysis standardized mean difference SMD = -0.74; 95%
CI, -0.97 to -0.5; p < 0.001). CONCLUSIONS: Systematic review of CSWT studies in
stable coronary artery disease (CAD) demonstrated consistent improvement of
clinical variables. Meta-analysis showed a moderate improvement of exercise
capacity. Overall, CSWT is a promising non-invasive option for patients with end
stage CAD, but evidence is limited to small sample single-center studies. Multi
center adequately powered randomised double blind studies are warranted.
PMID- 28403862
TI - MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study.
AB - BACKGROUND: Mucin 1 (MUC1) contributes to the growth and metastasis of various
cancers, including lung cancer, and MUC1 gene length polymorphisms are associated
with susceptibility to lung cancer and its prognosis. In contrast, the
association between rs4072037, a single nucleotide polymorphism in MUC1, and lung
cancer has not been well studied. METHODS: In the present study, we determined
the rs4072037 genotype and measured serum KL-6 levels to evaluate the association
between lung adenocarcinoma (ADC) and rs4072037 or serum KL-6 levels. DNA samples
were available for 172 patients and these were included in the genomic analyses.
In addition, 304 patients were included in the serum analyses. Furthermore, 276
healthy volunteers were included in both genomic and serum analyses. RESULTS: The
rs4072037 genotype was not associated with susceptibility to lung ADC or its
prognosis. Interestingly, serum KL-6 levels significantly differed according to
rs4072037 genotype in those with T1 or T2 (P < 0.001), N0 or N1 (P = 0.002) and
M0 (P < 0.001), but not in those with T3 or T4 (P = 0.882), N2 or N3 (P = 0.616)
and M1a or M1b (P = 0.501). Serum KL-6 levels were significantly associated with
the presence of lung ADC, as well as with its progression and prognosis,
indicating the crucial involvement of KL-6/MUC1 in the development of lung cancer
and its progression. CONCLUSION: Based on these findings, we conclude that
rs4072037 does not have a significant impact on the pathogenesis or prognosis of
lung ADC, whereas serum KL-6 levels, which might reflecting the molecular length
of MUC1, are significantly associated with lung ADC.
PMID- 28403863
TI - Laparoscopic resection of gastric duplication cysts in newborns: a report of five
cases.
AB - BACKGROUND: Gastric duplication cysts are rare congenital alimentary tract
anomalies and most cases are recognized during childhood. There were few reports
about gastric duplication cysts in newborns and even fewer reports about
laparoscopic resection of gastric duplication cysts in newborns. CASE
PRESENTATION: We report a series of five newborns with gastric duplication cysts
which were successfully resected by laparoscopy between January 2010 and April
2015. Case 1, a male newborn was admitted because of severe salivation, choking
cough and dyspnea for 30 min after birth. Case 2, a male, was suspected of
duodenal ileus by antenatal examination. Case 3, a female was admitted because of
vomiting for 5 days. Case 4,a female without significant symptoms simply visited
us for the abdominal cyst detected by antenatal examination. Case 5, a male was
admitted because of vomiting for 4 days. All patients were performed with a
surgery after assistant examinations. Case 1 was died of respiratory failure and
the other patients recovered uneventfully. CONCLUSION: Gastric duplication cysts
in newborns are very rare. Laparoscopic surgery play an important role on the
diagnosis and treatment. Our experience and practice indicate that laparoscopic
resection of gastric duplication cysts in newborns is viable and there is also a
need to increase sample size to prove its safety and effectiveness.
PMID- 28403864
TI - Health-related quality of life among Swedish children with Juvenile Idiopathic
Arthritis: parent-child discrepancies, gender differences and comparison with a
European cohort.
AB - BACKGROUND: This study investigates gender differences in self-reports and
between parent and child reports in Health-related Quality of Life (HRQOL),
measured with disease-specific and generic instruments for chronic disease.
Comparison of HRQOL results in this Juvenile Idiopathic Arthritis (JIA) sample to
a European cohort of children with JIA and one of children with other health
conditions are also made. METHODS: Fifty-three children with juvenile idiopathic
arthritis (JIA), aged 8-18 years, and their parents completed the condition
specific DISABKIDS for JIA, and the DISABKIDS generic instrument for chronic
conditions (DCGM-37) in a cross-sectional study. European reference data were
used for comparison of child and parental reports. RESULTS: Child self-reports in
DCGM-37 and DISABKIDS for JIA showed no gender differences. Parental and child
reports of the child's HRQOL differed only in DCGM-37; this was among girls who
scored their independence (p = 0.03), physical limitation (p = 0.01), social
exclusion (p = 0.03), emotions (p <0.01), and general transformed score (p <0.01)
higher than did their parents. Our sample of children with JIA reported more
physical limitation compared to samples of European children with JIA (p = 0.01),
European children with chronic conditions (p < 0.01), and their parents (p = 0.01
and p < 0.01). The Swedish children reported more problem with understanding
compared to the European JIA sample (p = 0.03). Swedish parents perceived their
children's independence significantly lower than did the European parents of JIA
children (p < 0.01), as well as European parents of children with chronic
conditions (p = 0.03). The Swedish parents also perceived their children to have
significantly lower social inclusion (p < 0.05) and general transformed score (p
= 0.04), in comparison to European parents of children with chronic conditions.
CONCLUSIONS: Parent-child differences in assessment of quality of life depend on
the HRQOL instrument used, especially among girls. In comparison to European
cohorts, our sample of children with JIA experienced more physical limitations
and less understanding.
PMID- 28403866
TI - Erratum to: Pre-hospital management of mass casualty civilian shootings: a
systematic literature review.
PMID- 28403865
TI - Implementing 360 degrees Quantified Self for childhood obesity: feasibility
study and experiences from a weight loss camp in Qatar.
AB - BACKGROUND: The explosion of consumer electronics and social media are
facilitating the rise of the Quantified Self (QS) movement where millions of
users are tracking various aspects of their daily life using social media, mobile
technology, and wearable devices. Data from mobile phones, wearables and social
media can facilitate a better understanding of the health behaviors of
individuals. At the same time, there is an unprecedented increase in childhood
obesity rates worldwide. This is a cause for grave concern due to its potential
long-term health consequences (e.g., diabetes or cardiovascular diseases).
Childhood obesity is highly prevalent in Qatar and the Gulf Region. In this study
we examine the feasibility of capturing quantified-self data from social media,
wearables and mobiles within a weight lost camp for overweight children in Qatar.
METHODS: Over 50 children (9-12 years old) and parents used a wide range of
technologies, including wearable sensors (actigraphy), mobile and social media
(WhatsApp and Instagram) to collect data related to physical activity and food,
that was then integrated with physiological data to gain insights about their
health habits. In this paper, we report about the acquired data and visualization
techniques following the 360 degrees Quantified Self (360QS) methodology
(Haddadi et al., ICHI 587-92, 2015). RESULTS: 360QS allows for capturing insights
on the behavioral patterns of children and serves as a mechanism to reinforce
education of their mothers via social media. We also identified human factors,
such as gender and cultural acceptability aspects that can affect the
implementation of this technology beyond a feasibility study. Furthermore,
technical challenges regarding the visualization and integration of heterogeneous
and sparse data sets are described in the paper. CONCLUSIONS: We proved the
feasibility of using 360QS in childhood obesity through this pilot study.
However, in order to fully implement the 360QS technology careful planning and
integration in the health professionals' workflow is needed. TRIAL REGISTRATION:
The trial where this study took place is registered at ClinicalTrials.gov on 14
November 2016 ( NCT02972164 ).
PMID- 28403867
TI - Accelerated triacylglycerol production and altered fatty acid composition in
oleaginous microalga Neochloris oleoabundans by overexpression of diacylglycerol
acyltransferase 2.
AB - BACKGROUND: Microalgae are promising sources of lipid triacylglycerol (TAG) for
biodiesel production. However, to date, microalgal biodiesel is technically
feasible, but not yet economically viable. Increasing TAG content and
productivity are important to achieve economic viability of microalgal biodiesel.
To increase TAG content, oleaginous microalga Neochloris oleoabundans was
genetically engineered with an endogenous key enzyme diacylglycerol
acyltransferase 2 (NeoDGAT2) responsible for TAG biosynthesis. RESULTS: The
integration of NeoDGAT2 expression cassettes in N. oleoabundans transformant was
confirmed by PCR. The neutral lipid accumulation in the transformant detected by
Nile red staining was accelerated and 1.9-fold higher than in wild type; the
lipid bodies in the transformant visualized under fluorescence microscope were
also larger. The NeoDGAT2 transcript was two-fold higher in the transformant than
wild type. Remarkably higher lipid accumulation was found in the transformant
than wild type: total lipid content increased 1.6-to 2.3-fold up to 74.5 +/- 4.0%
dry cell weight (DCW) and total lipid productivity increased 1.6- to 3.2-fold up
to 14.6 +/- 2.0 mg/L/day; while TAG content increased 1.8- to 3.2-fold up to 46.1
+/- 1.6% DCW and TAG productivity increased 1.6- to 4.3-fold up to 8.9 +/- 1.3
mg/L/day. A significantly altered fatty acid composition was detected in the
transformant compared to wild type; the levels of saturated fatty acid C16:0
increased double to 49%, whereas C18:0 was reduced triple to 6%. Long-term
stability was observed in the transformant continuously maintained in solid
medium over 100 generations in a period of about 4 years. CONCLUSIONS: Our
results demonstrate the increased TAG content and productivity in N. oleoabundans
by NeoDGAT2 overexpression that may offer the first step towards making
microalgae an economically feasible source for biodiesel production. The strategy
for genetically improved microalga presented in this study can be applied to
other microalgal species possessing desired characteristics for industrial
biofuel production.
PMID- 28403869
TI - Debulking surgery for venous hemangioma arising from the epicardium: report of a
case.
AB - BACKGROUND: Cardiac hemangiomas are rare benign vascular tumors that can occur in
any cardiac layer: endocardium, myocardium, or epicardium. Histologically,
cardiac hemangiomas may be classified as capillary, cavernous, or arteriovenous;
venous hemangiomas are extremely rare. CASE PRESENTATION: A 46-year-old man
reported experiencing precordial discomfort. Computed tomography revealed a
massive tumor adjacent to the right ventricle. The right coronary artery was
found to be located at the center of the tumor. Cardiovascular angiography showed
that the artery was completely encased by the tumor without any obstruction and
that the right ventricular lumen was compressed by the tumor. Surgical debulking
of the tumor was performed under cardiopulmonary bypass, and the frozen section
led to a diagnosis of benign hemangioma. The tumor was debulked as much as
possible until the right coronary artery appeared. For decompression of the
heart, the pericardium was left open to the thoracic cavity and unsutured.
Histopathologic examination revealed a diagnosis of epicardial venous hemangioma.
CONCLUSIONS: Cardiac hemangioma should be included in the differential diagnosis
of mediastinal tumor in reference to the location and flow of the coronary
artery. Surgical resection, or at least tumor debulking, is required to confirm
the diagnosis and prevent further complications and has a favorable clinical
outcome.
PMID- 28403868
TI - The use of viscoelastic haemostatic assays in goal-directing treatment with
allogeneic blood products - A systematic review and meta-analysis.
AB - BACKGROUND: Management of the critically bleeding patient can be encountered in
many medical and surgical settings. Common for these patients is a high risk of
dying from exsanguination secondary to developing coagulopathy. The purpose of
this meta-analysis was to systematically review and assess randomised controlled
trials (RCTs) performed on patients in acute need for blood transfusions due to
bleeding to evaluate the effect of viscoelastic haemostatic assay (VHA) guidance
on bleeding, transfusion requirements and mortality. METHODS: PubMed and EMBASE
were searched for RCTs that 1) randomised patients into receiving transfusions
based on either a VHA-guided (thromboelastography [TEG] or rotational
thromboelastometry [ROTEM]) algorithm (intervention group) or at the clinician's
discretion and/or based on conventional coagulation tests (control group) and 2)
adequately reported on the outcomes bleeding and/or transfusions and/or
mortality. Data on bleeding, transfusions and mortality were extracted from each
trial and included in a meta-analysis. RESULTS: Fifteen RCTs (n = 1238 patients)
were included. Nine trials referred to cardiothoracic patients, one to liver
transplantation, one to surgical excision of burn wounds and one to trauma. One
trial was conducted with cirrhotic patients, one with patients undergoing
scoliosis surgery while one trial randomised treatment in post-partum females
presenting with bleeding. The amount of transfused red blood cells (RBCs), fresh
frozen plasma (FFP) and bleeding volume was found to be significantly reduced in
the VHA-guided groups, whereas no significant difference was found for platelet
transfusion requirements or mortality.
PMID- 28403870
TI - Noise sensitivity, rather than noise level, predicts the non-auditory effects of
noise in community samples: a population-based survey.
AB - BACKGROUND: Excessive noise affects human health and interferes with daily
activities. Although environmental noise may not directly cause mental illness,
it may accelerate and intensify the development of latent mental disorders. Noise
sensitivity (NS) is considered a moderator of non-auditory noise effects. In the
present study, we aimed to assess whether NS is associated with non-auditory
effects. METHODS: We recruited a community sample of 1836 residents residing in
Ulsan and Seoul, South Korea. From July to November 2015, participants were
interviewed regarding their demographic characteristics, socioeconomic status,
medical history, and NS. The non-auditory effects of noise were assessed using
the Center of Epidemiologic Studies Depression, Insomnia Severity index, State
Trait Anxiety Inventory state subscale, and Stress Response Inventory-Modified
Form. Individual noise levels were recorded from noise maps. A three-model
multivariate logistic regression analysis was performed to identify factors that
might affect psychiatric illnesses. RESULTS: Participants ranged in age from 19
to 91 years (mean: 47.0 +/- 16.1 years), and 37.9% (n = 696) were male.
Participants with high NS were more likely to have been diagnosed with diabetes
and hyperlipidemia and to use psychiatric medication. The multivariable analysis
indicated that even after adjusting for noise-related variables, sociodemographic
factors, medical illness, and duration of residence, subjects in the high NS
group were more than 2 times more likely to experience depression and insomnia
and 1.9 times more likely to have anxiety, compared with those in the low NS
group. Noise exposure level was not identified as an explanatory value.
CONCLUSIONS: NS increases the susceptibility and hence moderates there actions of
individuals to noise. NS, rather than noise itself, is associated with an
elevated susceptibility to non-auditory effects.
PMID- 28403871
TI - A systematic tale of two differing reviews: evaluating the evidence on public and
private sector quality of primary care in low and middle income countries.
AB - Systematic reviews are powerful tools for summarizing vast amounts of data in
controversial areas; but their utility is limited by methodological choices and
assumptions. Two systematic reviews of literature on the quality of private
sector primary care in low and middle income countries (LMIC), published in the
same journal within a year, reached conflicting conclusions. The difference in
findings reflects different review methodologies, but more importantly, a weak
underlying body of literature. A detailed examination of the literature cited in
both reviews shows that only one of the underlying studies met the gold standard
for methodological robustness. Given the current policy momentum on universal
health coverage and primary health care reform across the globe, there is an
urgent need for high quality empirical evidence on the quality of private versus
public sector primary health care in LMIC.
PMID- 28403872
TI - Erratum to: Validation of the German version of two scales (RIS, RCS-HCP) for
measuring regret associated with providing healthcare.
PMID- 28403873
TI - Weight change during chemotherapy in breast cancer patients: a meta-analysis.
AB - BACKGROUND: Weight gain during chemotherapy in women with breast cancer is
commonly reported. However, there are important differences between studies that
examined weight change during chemotherapy; e.g. type of chemotherapy, menopausal
status, time between body weight measurements and sample size. The purpose of
this meta-analysis was to quantify changes in body weight during chemotherapy for
women with breast cancer, taking these differences into account. METHODS: We
identified relevant studies using PubMed, Scopus and Embase databases. The search
was limited to human studies published in English up to and including December
2015. Only studies among women with early stage breast cancer treated with
chemotherapy, with reported body weight before and after chemotherapy and type of
chemotherapy were included. Random-effect models were used, and heterogeneity
between studies was explored through stratified analyses and meta-regression.
Sensitivity analyses were done to explore whether a specific study markedly
affected the results. RESULTS: In total 25 papers were found, including data from
2620 women. Overall, body weight increased during chemotherapy: 2.7 kg (95% CI
2.0, 7.5) with a high degree of heterogeneity (I2 = 94.2%). Stratified analyses
showed weight gain in all strata, but did not substantially reduce heterogeneity.
Univariate meta-regression showed less weight gain in prospective studies
compared to chart review studies (-2.0, 95% CI: -3.1, -0.8). Studies including
cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimes showed a greater
weight gain compared to those that did not (2.2, 95% CI: 1.1, 3.3); and papers
published until the year 2000 showed a greater weight gain compared to those
published after 2000 (1.9, 95% CI:-0.8, 3.1). In the multivariate models only
studies including CMF regimes and studies published until 2000 were associated
with significant weight gain of respectively 1.3 and 1.4 kg. CONCLUSION: Despite
the high heterogeneity, this meta-analysis shows significant weight gain during
chemotherapy for women with breast cancer. Weight gain was more pronounced in
papers published until 2000 and women receiving CMF as chemotherapy regime.
Although weight gain after chemotherapy has decreased over the course of time,
weight gain is still substantial and deserves clinical attention.
PMID- 28403874
TI - Intranasal immunization of pigs with porcine reproductive and respiratory
syndrome virus-like particles plus 2', 3'-cGAMP VacciGradeTM adjuvant exacerbates
viremia after virus challenge.
AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes
reproductive failure in pregnant sows and acute respiratory disease in young
pigs. It is a leading infectious agent of swine respiratory complex, which has
significant negative economic impact on the swine industry. Commercial markets
currently offer both live attenuated and killed vaccines; however, increasing
controversy exists about their efficacy providing complete protection. Virus-like
particles (VLPs) possess many desirable features of a potent vaccine candidate
and have been proven to be highly immunogenic and protective against virus
infections. Here we explored the efficacy of PRRSV VLPs together with the use of
a novel 2', 3'-cGAMP VacciGradeTM adjuvant. METHODS: Animals were immunized twice
intranasally with phosphate buffered saline (PBS), PRRSV VLPs, or PRRSV VLPs plus
2', 3'-cGAMP VacciGradeTM at 2 weeks apart. Animals were challenged with PRRSV
23983 at 2 weeks post the second immunization. PRRSV specific antibody response
and cytokines were measured. Viremia, clinical signs, and histological lesions
were evaluated. RESULTS: PRRSV N protein specific antibody was detected in all
animals at day 10 after challenge, but no significant difference was observed
among the vaccinated and control groups. Surprisingly, a significantly higher
viremia was observed in the VLPs and VLPs plus the adjuvant groups compared to
the control group. The increased viremia is correlated with a higher interferon
alpha induction in the serum of the VLPs and the VLPs plus the adjuvant groups.
CONCLUSIONS: Intranasal immunizations of pigs with PRRSV VLPs and VLPs plus the
2', 3'-cGAMP VacciGradeTM adjuvant exacerbates viremia. A higher level of
interferon-alpha production, but not interferon-gamma and IL-10, is correlated
with enhanced virus replication. Overall, PRRSV VLPs and PRRSV VLPs plus the
adjuvant fail to provide protection against PRRSV challenge. Different dose of
VLPs and alternative route of vaccination such as intramuscular injection should
be explored in the future studies to fully assess the feasibility of such a
vaccine platform for PRRSV control and prevention.
PMID- 28403875
TI - Determining the presence of asthma-related molecules and salivary contamination
in exhaled breath condensate.
AB - BACKGROUND: Researchers investigating lung diseases, such as asthma, have
questioned whether certain compounds previously reported in exhaled breath
condensate (EBC) originate from saliva contamination. Moreover, despite its
increasing use in 'omics profiling studies, the constituents of EBC remain
largely uncharacterized. The present study aims to define the usefulness of EBC
in investigating lung disease by comparing EBC, saliva, and saliva-contaminated
EBC using targeted and untargeted mass spectrometry and the potential of
metabolite loss from adsorption to EBC sample collection tubes. METHODS: Liquid
chromatography mass spectrometry (LC-MS) was used to analyze samples from 133
individuals from three different cohorts. Levels of amino acids and eicosanoids,
two classes of molecules previously reported in EBC and saliva, were measured
using targeted LC-MS. Cohort 1 was used to examine contamination of EBC by
saliva. Samples from Cohort 1 consisted of clean EBC, saliva-contaminated EBC,
and clean saliva from 13 healthy volunteers; samples were analyzed using
untargeted LC-MS. Cohort 2 was used to compare eicosanoid levels from matched EBC
and saliva collected from 107 asthmatic subjects. Samples were analyzed using
both targeted and untargeted LC-MS. Cohort 3 samples consisted of clean-EBC
collected from 13 subjects, including smokers and non-smokers, and were used to
independently confirm findings; samples were analyzed using targeted LC-MS,
untargeted LC-MS, and proteomics. In addition to human samples, an in-house
developed nebulizing system was used to determine the potential for EBC samples
to be contaminated by saliva. RESULTS: Out of the 400 metabolites detected in
both EBC and saliva, 77 were specific to EBC; however, EBC samples were
concentrated 20-fold to achieve this level of sensitivity. Amino acid
concentrations ranged from 196 pg/mL - 4 MUg/mL (clean EBC), 1.98 ng/mL - 6
MUg/mL (saliva-contaminated EBC), and 13.84 ng/mL - 1256 mg/mL (saliva).
Eicosanoid concentration ranges were an order of magnitude lower; 10 pg/mL - 76.5
ng/mL (clean EBC), 10 pg/mL - 898 ng/mL (saliva-contaminated EBC), and 2.54 ng/mL
- 272.9 mg/mL (saliva). Although the sample size of the replication cohort
(Cohort 3) did not allow for statistical comparisons, two proteins and 19
eicosanoids were detected in smoker vs. non-smoker clean-EBC. CONCLUSIONS: We
conclude that metabolites are present and detectable in EBC using LC-MS; however,
a large starting volume of sample is required.
PMID- 28403876
TI - Development of a core outcome set for effectiveness trials aimed at optimising
prescribing in older adults in care homes.
AB - BACKGROUND: Prescribing medicines for older adults in care homes is known to be
sub-optimal. Whilst trials testing interventions to optimise prescribing in this
setting have been published, heterogeneity in outcome reporting has hindered
comparison of interventions, thus limiting evidence synthesis. The aim of this
study was to develop a core outcome set (COS), a list of outcomes which should be
measured and reported, as a minimum, for all effectiveness trials involving
optimising prescribing in care homes. The COS was developed as part of the Care
Homes Independent Pharmacist Prescribing Study (CHIPPS). METHODS: A long-list of
outcomes was identified through a review of published literature and stakeholder
input. Outcomes were reviewed and refined prior to entering a two-round online
Delphi exercise and then distributed via a web link to the CHIPPS Management
Team, a multidisciplinary team including pharmacists, doctors and Patient Public
Involvement representatives (amongst others), who comprised the Delphi panel. The
Delphi panellists (n = 19) rated the importance of outcomes on a 9-point Likert
scale from 1 (not important) to 9 (critically important). Consensus for an
outcome being included in the COS was defined as >=70% participants scoring 7-9
and <15% scoring 1-3. Exclusion was defined as >=70% scoring 1-3 and <15% 7-9.
Individual and group scores were fed back to participants alongside the second
questionnaire round, which included outcomes for which no consensus had been
achieved. RESULTS: A long-list of 63 potential outcomes was identified.
Refinement of this long-list of outcomes resulted in 29 outcomes, which were
included in the Delphi questionnaire (round 1). Following both rounds of the
Delphi exercise, 13 outcomes (organised into seven overarching domains:
medication appropriateness, adverse drug events, prescribing errors, falls,
quality of life, all-cause mortality and admissions to hospital (and associated
costs)) met the criteria for inclusion in the final COS. CONCLUSIONS: We have
developed a COS for effectiveness trials aimed at optimising prescribing in older
adults in care homes using robust methodology. Widespread adoption of this COS
will facilitate evidence synthesis between trials. Future work should focus on
evaluating appropriate tools for these key outcomes to further reduce
heterogeneity in outcome measurement in this context.
PMID- 28403878
TI - Rescue strategy for advanced liver malignancy with retrohepatic inferior vena
cava thrombi: experience to promote surgical oncological benefit.
AB - BACKGROUND: The prognosis of advanced liver malignancy with inferior vena cava
(IVC) thrombi is poor. Many therapeutic policies are challenging for long-term
prognosis. We performed the modified effective technique of transdiaphragmatic
intrapericardial IVC isolation for curative resection of IVC tumors and prolonged
survival time. METHODS: Between 2003 and 2015, 10 patients, sustained liver
malignancy with IVC thrombi, underwent surgical intervention. Liver resection
with thrombectomy under total hepatic vascular exclusion via the
transdiaphragmatic intrapericardial IVC isolation method was performed for these
10 patients. The first 4 patients underwent retrohepatic IVC resection in order
to complete resection, and the other 6 patients preserved the retrohepatic IVC.
The last 3 patients received preoperative locoregional therapies, and all 10
patients received postoperative adjuvant chemotherapies immediately. RESULTS: All
10 patients underwent gross en bloc tumor resections with thrombectomy with R0
resection. There was no surgical mortality. Shortening of operation time and
reduction of both intraoperative blood loss and hospital stay were demonstrated
in the last 6 patients with preserving the retrohepatic IVC. However, similar
time to recurrence and survival time were noted in the first 7 patients. The last
3 patients, who had received preoperative locoregional therapies, have better
disease-free survival time. CONCLUSION: Simplified surgical procedure combined
with preoperative locoregional therapies and rapid postoperative adjuvant
treatment may provide a greater advantage for these patients.
PMID- 28403877
TI - A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile
in patients with type 2 diabetes.
AB - BACKGROUND: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4)
inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different
effects on the lipid profile in patients with type 2 diabetes. We investigated
the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in
patients with type 2 diabetes. METHODS: From January 2013 to December 2015, a
total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor
or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were
consecutively enrolled. We compared the effects of DPP-4 inhibitors and SGLT2
inhibitors on the lipid profile at baseline and after 24 weeks of treatment. To
compare lipid parameters between the two groups, we used the analysis of
covariance (ANCOVA). RESULTS: A total of 184 patients completed follow-up (mean
age: 53.1 +/- 6.9 years, mean duration of diabetes: 7.1 +/- 5.7 years). From
baseline to 24 weeks, HDL-cholesterol (HDL-C) levels were increased by 0.5 (95%
CI, -0.9 to 2.0) mg/dl with a DPP-4 inhibitor and by 5.1 (95% CI, 3.0 to 7.1)
mg/dl with an SGLT2 inhibitor (p = 0.001). LDL-cholesterol (LDL-C) levels were
reduced by 8.4 (95% CI, -14.0 to -2.8) mg/dl with a DPP-4 inhibitor, but
increased by 1.3 (95% CI, -5.1 to 7.6) mg/dl with an SGLT2 inhibitor (p = 0.046).
There was no significant difference in the mean hemoglobin A1c (8.3 +/- 1.1 vs.
8.0 +/- 0.9%, p = 0.110) and in the change of total cholesterol (TC) (p = 0.836),
triglyceride (TG) (p = 0.867), apolipoprotein A (p = 0.726), apolipoprotein B (p
= 0.660), and lipoprotein (a) (p = 0.991) between the DPP-4 inhibitor and the
SGLT2 inhibitor. CONCLUSIONS: The SGLT2 inhibitor was associated with a
significant increase in HDL-C and LDL-C after 24 weeks of SGLT2 inhibitor
treatment in patients with type 2 diabetes compared with those with DPP-4
inhibitor treatment in this study. TRIAL REGISTRATION: This study was conducted
by retrospective medical record review.
PMID- 28403879
TI - Spatial clustering and risk factors of malaria infections in Bata district,
Equatorial Guinea.
AB - BACKGROUND: The transmission of malaria is intense in the majority of the
countries of sub-Saharan Africa, particularly in those that are located along the
Equatorial strip. The present study aimed to describe the current distribution of
malaria prevalence among children and its environment-related factors as well as
to detect malaria spatial clusters in the district of Bata, in Equatorial Guinea.
METHODS: From June to August 2013 a representative cross-sectional survey using a
multistage, stratified, cluster-selected sample was carried out of children in
urban and rural areas of Bata District. All children were tested for malaria
using rapid diagnostic tests (RDTs). Results were linked to each household by
global position system data. Two cluster analysis methods were used: hot spot
analysis using the Getis-Ord Gi statistic, and the SaTScanTM spatial statistic
estimates, based on the assumption of a Poisson distribution to detect spatial
clusters. In addition, univariate associations and Poisson regression model were
used to explore the association between malaria prevalence at household level
with different environmental factors. RESULTS: A total of 1416 children aged 2
months to 15 years living in 417 households were included in this study. Malaria
prevalence by RDTs was 47.53%, being highest in the age group 6-15 years (63.24%,
p < 0.001). Those children living in rural areas were there malaria risk is
greater (65.81%) (p < 0.001). Malaria prevalence was higher in those houses
located <1 km from a river and <3 km to a forest (IRR: 1.31; 95% CI 1.13-1.51 and
IRR: 1.44; 95% CI 1.25-1.66, respectively). Poisson regression analysis also
showed a decrease in malaria prevalence with altitude (IRR: 0.73; 95% CI 0.62
0.86). A significant cluster inland of the district, in rural areas has been
found. CONCLUSIONS: This study reveals a high prevalence of RDT-based malaria
among children in Bata district. Those households situated in inland rural areas,
near to a river, a green area and/or at low altitude were a risk factor for
malaria. Spatial tools can help policy makers to promote new recommendations for
malaria control.
PMID- 28403880
TI - Lower limb function and quality of life after ILP for soft-tissue sarcoma.
AB - BACKGROUND: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) in
combination with complete tumor resection is an effective treatment option for
non-resectable soft-tissue sarcoma of the extremities, with limb salvage rates
greater than 80%. The aim of this study was to assess quality of life (QoL) after
TM-ILP, also with regard to long-term survival. METHODS: We retrospectively
examined 27 patients who had primarily non-resectable soft-tissue sarcoma of the
leg and who had undergone TM-ILP and complete tumor resection (with limb-sparing
intent) during their follow-up examinations using the Quality of Life
Questionnaire (QLQ-C30) and the German Short Musculoskeletal Function Assessment
(SMFA-D). The results from the QLQ-C30 were compared to the reference values for
the general population, to the "all cancer patients" reference values (both
reference values published by the European Organization for Research and
Treatment of Cancer (EORTC)), and to the reference values of a historical
amputation group from the literature. The results of the SMFA were compared with
those from a reference group of healthy individuals. RESULTS: Surprisingly, we
found that the global health status/QoL in the TM-ILP group was not significantly
different from the general population or from patients with amputation, but it
was higher than that of patients with cancer in general. Concerning the SMFA, we
did find functional impairments in patients after TM-ILP compared to the
reference group. With regard to long-term survival, we found no time-dependent
deterioration in QoL for longer time intervals after treatment. CONCLUSIONS:
These results support the use of TM-ILP in limb-sparing multimodal therapy
settings from a quality-of-life perspective, but they also encourage further
research on this matter.
PMID- 28403881
TI - Glucocorticoid receptor represses brain-derived neurotrophic factor expression in
neuron-like cells.
AB - Brain-derived neurotrophic factor (BDNF) is involved in many functions such as
neuronal growth, survival, synaptic plasticity and memorization. Altered
expression levels are associated with many pathological situations such as
depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases.
Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of
glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has
been proposed that GR could be a regulator of BDNF expression, however the
molecular mechanisms involved have not been clearly defined yet. Herein, we
analyzed the effect of a GC agonist dexamethasone (DEX) on BDNF expression in
mouse neuronal primary cultures and in the newly characterized, mouse hippocampal
BZ cell line established by targeted oncogenesis. Mouse Bdnf gene exhibits a
complex genomic structure with 8 untranslated exons (I to VIII) splicing onto one
common and unique coding exon IX. We found that DEX significantly downregulated
total BDNF mRNA expression by around 30%. Expression of the highly expressed exon
IV and VI containing transcripts was also reduced by DEX. The GR antagonist RU486
abolished this effect, which is consistent with specific GR-mediated action.
Transient transfection assays allowed us to define a short 275 bp region within
exon IV promoter responsible for GR-mediated Bdnf repression. Chromatin
immunoprecipitation experiments demonstrated GR recruitment onto this fragment,
through unidentified transcription factor tethering. Altogether, GR downregulates
Bdnf expression through direct binding to Bdnf regulatory sequences. These
findings bring new insights into the crosstalk between GR and BDNF signaling
pathways both playing a major role in physiology and pathology of the central
nervous system.
PMID- 28403882
TI - Pathobiological investigation of naturally infected canine rabies cases from Sri
Lanka.
AB - BACKGROUND: The recommended screening of rabies in 'suspect' animal cases
involves testing fresh brain tissue. The preservation of fresh tissue however can
be difficult under field conditions and formalin fixation provides a simple
alternative that may allow a confirmatory diagnosis. The occurrence and location
of histopathological changes and immunohistochemical (IHC) labelling for rabies
in formalin fixed paraffin embedded (FFPE) canine brain is described in samples
from 57 rabies suspect cases from Sri-Lanka. The presence of Negri bodies and
immunohistochemical detection of rabies virus antigen were evaluated in the
cortex, hippocampus, cerebellum and brainstem. The effect of autolysis and
artefactual degeneration of the tissue was also assessed. RESULTS: Rabies was
confirmed in 53 of 57 (93%) cases by IHC. IHC labelling was statistically more
abundant in the brainstem. Negri bodies were observed in 32 of 53 (60.4%) of the
positive cases. Although tissue degradation had no effect on IHC diagnosis, it
was associated with an inability to detect Negri bodies. In 13 cases, a
confirmatory Polymerase chain reaction (PCR) testing for rabies virus RNA was
undertaken by extracting RNA from fresh frozen tissue, and also attempted using
FFPE samples. PCR detection using fresh frozen samples was in agreement with the
IHC results. The PCR method from FFPE tissues was suitable for control material
but unsuccessful in our field cases. CONCLUSIONS: Histopathological examination
of the brain is essential to define the differential diagnoses of behaviour
modifying conditions in rabies virus negative cases, but it is unreliable as the
sole method for rabies diagnosis, particularly where artefactual change has
occurred. Formalin fixation and paraffin embedding does not prevent detection of
rabies virus via IHC labelling even where artefactual degeneration has occurred.
This could represent a pragmatic secondary assay for rabies diagnosis in the
field because formalin fixation can prevent sample degeneration. The brain stem
was shown to be the site with most viral immunoreactivity; supporting recommended
sampling protocols in favour of improved necropsy safety in the field. PCR
testing of formalin fixed tissue may be successful in certain circumstances as an
alternative test.
PMID- 28403883
TI - DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4
in gastric cancer liver metastasis.
AB - BACKGROUND: Profiling evidences of selectin demonstrate that they play an crucial
role in cancer progression and metastasis. However, DC-SIGNR as a family member
of selectin participates in gastric cancer liver metastasis remains unknown.
METHODS: The serum level of DC-SIGNR was evaluated in gastric cancer patients by
ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was
mediated by lentivirus. Investigation the biological effects of DC-SIGNR were
verified by MTT, wounding and transwell in vitro and experiments on animals to
confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were
employed microarray and bioinformatic analysis. Further to confirm the results
were conducted by qRT-PCR, western blot and by flow cytometry. RESULTS: DC-SIGNR
serum level was significantly increased in gastric cancer patients compared with
healthy group. Additionally, DC-SIGNR level was associated with an advanced
pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the
proliferation, migration and invasion of gastric cancer cells in vitro and
suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted
cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA
was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2
expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the
downstream target gene CXCR4 was downregulated. CONCLUSIONS: DC-SIGNR promoted
gastric cancer liver metastasis mediated with HNRNPKP2 which expression was
regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target
gene CXCR4. These findings indicated potential therapeutic candidates for gastric
cancer liver metastasis.
PMID- 28403884
TI - IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by
pyrosequencing.
AB - BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade
glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other
than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma
(iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically,
poor differentiation and clear cell change are associated with IDH1 mutation in
iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC,
some specific subtypes of HCC might show a higher IDH1 mutation rate than
reported before (0.5-1.5%). METHODS: Forty-six cases of iCC and 48 cases of HCC
(including 20 cases of clear cell type and 13 cases of pseudoglandular pattern)
were tested for IDH1 mutation by pyrosequencing. RESULTS: Three cases in iCC
(6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were
Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation
rate between iCC and HCC demonstrated no significant difference, clear cell HCC
revealed statistically increased mutation rate compared to that of HCC without
clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor
survival in clear cell HCC patients (P = 0.004). CONCLUSIONS: Clear cell HCC
showed higher frequency of IDH1 mutation rate than other variants of HCC. This
result consolidates the assumption that morphological features of tumors reflect
molecular alterations.
PMID- 28403885
TI - Lung structure and function similarities between primary ciliary dyskinesia and
mild cystic fibrosis: a pilot study.
AB - BACKGROUND: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are
increasingly compared. There are no chest magnetic resonance imaging (MRI)
comparative studies of PCD and CF. We assessed clinical, functional,
microbiological and MRI findings in PCD and mild CF patients in order to evaluate
different expression of lung disease. METHODS: Twenty PCD (15.1 years) and 20 CF
subjects with mild respiratory impairment (16 years, 70% with pancreatic
insufficiency) underwent MRI, spirometry, and sputum cultures when clinically
stable. MRI was scored using the modified Helbich system. RESULTS: PCD was
diagnosed later than CF (9.9 versus 0.6 years, p = 0.03), despite earlier
symptoms (0.1 versus 0.6 years, p = 0.02). In the year preceding the study,
patients from both groups underwent two systemic antibiotic courses (p = 0.48).
MRI total scores were 11.6 +/- 0.7 and 9.1 +/- 1 in PCD and CF, respectively.
FEV1 and FVC Z-scores were -1.75 (range, -4.6-0.7) and -0.6 (-3.9-1.8) in PCD,
and -0.9 (range, -5.4-2.3) and -0.3 (-3.4-2.5) in CF, respectively. No difference
was found between lung function or structure, despite a higher MRI subscore of
collapse/consolidation in PCD versus CF (1.6 +/- 0.1 and 0.6 +/- 0.2, p < 0.001).
These findings were confirmed after data-control for diagnostic delay.
Pseudomonas aeruginosa and Staphylococcus aureus were more frequent in CF than in
PCD (p = 0.05 and p = 0.003, respectively). CONCLUSIONS: MRI is a valuable
radiation-free tool for comparative PCD and CF lung disease assessment. Patients
with PCD may exhibit similar MRI and lung function changes as CF subjects with
mild pulmonary disease. Delay in PCD diagnosis is unlikely the only determinant
of similarities.
PMID- 28403886
TI - The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR
200a-dependent HMGB1/RAGE regulation.
AB - BACKGROUND: P73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1,
is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the
development of tumors. However, the exact effects and molecular mechanisms of
TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The
present study is aimed to investigate the detailed functions and the mechanism of
TP73-AS1 in regulation of HCC cell proliferation. METHODS: TP73-AS1 expression in
HCC tissues and cell lines was determined using real-time PCR assays; the
correlation of TP73-AS1 expression with clinicopathological features of HCC was
analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was
evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were
screened using miRcode, miRWalk, miRanda and Target scan, verified using real
time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed
using Luciferase report gene assays. The proten levels of HMGB1 signaling-related
factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition
were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1
mRNA and RAGE mRNA and their correlations in HCC tissues were determined.
RESULTS: TP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1
expression was correlated with worse clinicopathological features, poorer
prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC
proliferation and the expression levels of HMGB1, RAGE and NF-kappaB in HCC
cells. By using online tools, we screened out several candidate upstream miRNAs
of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the
most significantly. By using luciferase assays, we confirmed that miR-200a could
directly bind to TP73-AS1 and the 3'UTR of HMGB1; TP73-AS1 competed with HMGB1
for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF
kappaB expression as well as NF-kappaB regulated cytokines levels, which could be
partially restored by si-TP73-AS1. In HCC tissues, miR-200a was down-regulated
while HMGB1 and RAGE were up-regulated; TP73-AS1 was inversely correlated with
miR-200a, while positively correlated with HMGB1 and RAGE, respectively.
CONCLUSION: Our data indicated that TP73-AS1 might be an oncogenic lncRNA that
promoted proliferation of HCC and could be regarded as a therapeutic target in
human HCC.
PMID- 28403887
TI - Global analysis of H3K27me3 as an epigenetic marker in prostate cancer
progression.
AB - BACKGROUND: H3K27me3 histone marks shape the inhibition of gene transcription. In
prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate
tumor progression. METHODS: We investigated genome-wide H3K27me3 histone
methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K
promoter microarrays to identify differentially-enriched regions in biopsy
samples from prostate cancer patients. H3K27me3 marks were assessed in 34
prostate tumors: 11 with Gleason score > 7 (GS > 7), 10 with Gleason score <= 7
(GS <= 7), and 13 morphologically normal prostate samples. RESULTS: Here,
H3K27me3 profiling identified an average of 386 enriched-genes on promoter
regions in healthy control group versus 545 genes in GS <= 7 and 748 genes in GS
> 7 group. We then ran a factorial discriminant analysis (FDA) and compared the
enriched genes in prostate-tumor biopsies and normal biopsies using ANOVA to
identify significantly differentially-enriched genes. The analysis identified
ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1,
SPATS2, TENM4 and TRA2A genes. These genes are possibly associated with prostate
cancer. Notably, the H3K27me3 histone mark emerged as a novel regulatory
mechanism in poor-prognosis prostate cancer. CONCLUSIONS: Our findings point to
epigenetic mark H3K27me3 as an important event in prostate carcinogenesis and
progression. The results reported here provide new molecular insights into the
pathogenesis of prostate cancer.
PMID- 28403888
TI - The relationship between ethnic composition of the residential environment and
self-reported health among Turks and Moroccans in Amsterdam.
AB - BACKGROUND: Previous studies from the US and UK suggest that neighbourhood ethnic
composition is associated with health, positive or negative, depending on the
health outcome and ethnic group. We examined the association between
neighbourhood ethnic composition and self-reported health in these groups in
Amsterdam, and we aimed to explore whether there is spatial variation in this
association. METHODS: We used micro-scale data to describe the ethnic composition
in buffers around the home location of 2701 Turks and 2661 Moroccans. Multilevel
regression analysis was used to assess the association between three measures of
ethnic composition (% co-ethnics, % other ethnic group, Herfindahl index) and
three measures of self-reported health: self-rated health, Physical and Mental
Component Score (PCS, MCS). We adjusted for socioeconomic position at individual
and area level. We used geographically weighted regression and spatially
stratified regression analyses to explore whether associations differed within
Amsterdam. RESULTS: Ethnic heterogeneity and own ethnic density were not related
to self-rated health for both ethnic groups. Higher density of Turks was
associated with better self-rated health among Moroccans at all buffer sizes,
with the most significant relations for small buffers. Higher heterogeneity was
associated with lower scores on PCS and MCS among Turks (suggesting worse
health). We found spatial variation in the association of the density of the
other ethnic group with self-rated health of Moroccans and Turks. We found a
positive association for both groups, spatially concentrated in the sub-district
Geuzenveld. CONCLUSIONS: Our study showed that the association of ethnic
composition with self-reported health among Turks and Moroccans in Amsterdam
differed between the groups and reveals mainly at small spatial scales. Among
both groups, an association of higher density of the other group with better self
rated health was found in a particular part of Amsterdam, which might be
explained by the presence of a relatively strong sense of community between the
two groups in that area. The study suggests that it is important to pay attention
to other-group density, to use area measurements at small spatial scales and to
examine the spatial variation in these associations. This may help to identify
neighbourhood characteristics contributing to these type of area effects on urban
minority health.
PMID- 28403889
TI - Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis
(JDM).
AB - BACKGROUND: The course of JDM has improved substantially over the last 70 years
with early and aggressive treatments. Yet it remains difficult to detect disease
flares as symptoms may be mild; signs of rash and muscle weakness vary widely and
are often equivocal; laboratory tests of muscle enzyme levels are often normal;
electromyography and muscle biopsy are invasive. Alternative tools are needed to
help decide if more aggressive treatment is needed. Our objective is to determine
the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM
flares, and how an MRI affects physician's decision-making regarding treatment.
METHODS: This study was approved by the Institutional Review Board of Nationwide
Children's Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs
were performed on both lower extremities without contrast sequentially: axial T1,
axial T2 fat saturation, axial and coronal inversion recovery, and axial
diffusion weighted. The physician decision that a JDM patient was in a flare was
considered the gold standard. MRI results were compared with physician's
decisions on whether a relapse had occurred, and if there was a concordance
between the assessment methods. RESULTS: Forty-five JDM patients were studied.
Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail
fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM
generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in
3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating
myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with
differing indications. Three repeat MRI's were abnormal, demonstrating myositis.
There was moderate agreement about flares between MRI findings and physician's
treatment decisions (kappa = 0.59). In each abnormal MRI case the physician
decided to increase treatment (100% probability for flares). MRI was negative for
myositis in 10 patients, by which 7/10 the physicians chose to continue or to
taper the medications (70% probability for non-flares). CONCLUSION: A muscle MRI
would facilitate objective assessments of JDM flares. When an MRI shows myositis,
physicians tend to treat 100% of the time. When an MRI shows no myositis,
physicians continued the same medications or tapered medications 70% of the time.
Further studies would help confirm the utility and cost-effectiveness of MRI to
determine JDM flares.
PMID- 28403891
TI - Foley catheter for cervical priming in induction of labour at University
Obstetrics Unit, Colombo, Sri Lanka: a clinical audit with a patient satisfaction
survey.
AB - BACKGROUND: Intracervical insertion of a Foley catheter (FC) has shown to be a
safe, effective and relatively feasible mechanical method of cervical priming in
induction of labour (IOL). We evaluated indications, effectiveness, patient
acceptability and outcomes of FC use in IOL adhering to the ward protocol in our
unit. METHODS: A clinical audit with a patient satisfaction survey conducted
between July and September 2013 in University Obstetric Unit, Colombo, Sri Lanka.
Patients selected for IOL for obstetric reasons were primed with Foley as per
ward protocol. All had singleton pregnancies with cephalic presentation, intact
membranes and period of gestation of 37 weeks or above. Women with a history of
more than one caesarean section or uterine surgery, low-lying placenta and fetal
growth restriction were excluded. Subjects who had a Modified Bishop Score (MBS)
of less than 3, a 16Fr FC was inserted into cervical canal. Catheter was left
undisturbed until spontaneous expulsion or no longer than 48 h. In women with MBS
of less than 6 at 48 h after FC insertion, 3 mg prostaglandin E2 vaginal tablet
was used subsequently. Artificial membrane rupture with or without oxytocin was
used if MBS of 6 or more and in women not in labour 24 h after prostaglandins.
Patient satisfaction for Foley insertion was assessed with regards to the degree
of comfort using a validated visual analogue scale (0-10). RESULTS: There were a
total of 910 deliveries during the study period. Fifty-six women were primed with
FC. Thirty-two (57%) were nulliparous. During induction of labour, 53(95%)
reported mild or no discomfort. MBS of 6 or more was achieved in 36/56 (64%)
Foley insertions. Twenty needed further intervention with prostaglandins. FC only
group had 5 caesarean sections and 31 vaginal deliveries and Foley/prostaglandin
group had 7 caesarean sections and 13 vaginal deliveries. Of the 24 women who
were induced due to completion of 41 weeks of gestation with otherwise
uncomplicated pregnancies, 17 had MBS >6 post priming with Foley and 20 (83%)
delivered vaginally. Subjects who had Foley only had a lesser chance of having a
caesarean delivery compared to subjects who had Foley followed by prostaglandin
(relative risk = 0.40, 95% CI = 0.15-1.09, P = 0.09). DISCUSSION: FC is a good
choice for pre-induction cervical priming with high patient comfort. FC becomes
more important in IOL cost reduction in our setting. FC alone seems to be an
effective for IOL in women who have completed 41 weeks of gestation with
otherwise uncomplicated pregnancies.
PMID- 28403890
TI - Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma
cells - synergism with autophagy inhibition.
AB - BACKGROUND: Osteosarcoma is the most frequent primary malignant bone tumor.
Although survival has distinctly increased due to neoadjuvant chemotherapy in the
past, patients with metastatic disease and poor response to chemotherapy still
have an adverse prognosis. Hence, development of new therapeutic strategies is
still of utmost importance. METHODS: Anticancer activity of KP46 against
osteosarcoma cell models was evaluated as single agent and in combination
approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay.
Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays.
RESULTS: KP46 exerted exceptional anticancer activity at the nanomolar to low
micromolar range, depending on the assay format, against all osteosarcoma cell
models with minor but significant differences in IC50 values. KP46 treatment of
osteosarcoma cells caused rapid loss of cell adhesion, weak cell cycle
accumulation in S-phase and later signs of apoptotic cell death. Furthermore,
already at sub-cytotoxic concentrations KP46 reduced the migratory potential of
osteosarcoma cells and exerted synergistic effects with cisplatin, a standard
osteosarcoma chemotherapeutic. Moreover, the gallium compound induced signs of
autophagy in osteosarcoma cells. Accordingly, blockade of autophagy by
chloroquine but also by the Bcl-2 inhibitor obatoclax increased the cytotoxic
activity of KP46 treatment significantly, suggesting autophagy induction as a
protective mechanism against KP46. CONCLUSION: Together, our results identify
KP46 as a new promising agent to supplement standard chemotherapy and possible
future targeted therapy in osteosarcoma.
PMID- 28403892
TI - Lipids bearing extruded-spheronized pellets for extended release of poorly
soluble antiemetic agent-Meclizine HCl.
AB - BACKGROUND: Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is
available only in immediate release dosage forms. The approved therapeutic dose
and shorter elimination half-life make Meclizine HCl a potential candidate to be
formulated in extended release dosage form. This study was aimed to develop
extended release Meclizine HCl pellets by extrusion spheronization using natural
and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations
of different lipids on drug release and sphericity of pellets were evaluated.
METHODS: Thirty two formulations were prepared with four different lipids,
Glyceryl monostearate (Geleol(r)), Glyceryl palmitostearate (Precirol(r)),
Glyceryl behenate (Compritol(r)) and Carnauba wax, utilized either alone or in
combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed
at variable pH and release kinetics were analyzed. Fourier transform infrared
spectroscopy was conducted and no drug lipid interaction was found. RESULTS:
Sphericity indicated by shape factor (eR) varied with type and concentration of
lipids: Geleol(r) (eR = 0.891-0.997), Precirol(r) (eR = 0.611-0.743),
Compritol(r) (eR = 0.665-0.729) and Carnauba wax (eR = 0.499-0.551). Highly
spherical pellets were obtained with Geleol(r) (Aspect ratio = 1.005-1.052)
whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio =
1.153-1.309). Drug release was effectively controlled by three different
combinations of lipids: (i) Geleol(r) and Compritol(r), (ii) Geleol(r) and
Carnauba wax and (iii) Geleol(r), Compritol(r) and Carnauba wax. Scanning
electron microscopy of Compritol(r) pellets showed smooth surface with pores,
whereas, irregular rough surface with hollow depressions was observed in Carnauba
wax pellets. Energy dispersive spectroscopy indicated elemental composition of
lipid matrix pellets. Kinetics of (i) Geleol(r) and Compritol(r) pellets,
explained by Korsmeyer-Peppas (R2 = 0.978-0.993) indicated non-Fickian diffusion
(n = 0.519-0.597). Combinations of (ii) Geleol(r) and Carnauba wax and (iii)
Geleol(r), Compritol(r) and Carnauba wax pellets followed Zero-order (R2 = 0.991
0.995). Similarity test was performed using combination of Geleol(r) and
Compritol(r) (i) as a reference. CONCLUSIONS: Matrices for the extended release
of Meclizine HCl from extruded-spheronized pellets were successfully formed by
using three lipids (Geleol(r), Compritol(r) and Carnauba wax) in different
combinations. The encapsulated pellets of Meclizine HCl can be effectively used
for treatment of motion sickness, nausea and vertigo for extended period of time.
PMID- 28403893
TI - Approaches to interpreting and choosing the best treatments in network meta
analyses.
AB - When randomized trials have addressed multiple interventions for the same health
problem, network meta-analyses (NMAs) permit researchers to statistically pool
data from individual studies including evidence from both direct and indirect
comparisons. Grasping the significance of the results of NMAs may be very
challenging. Authors may present the findings from such analyses in several
numerical and graphical ways. In this paper, we discuss ranking strategies and
visual depictions of rank, including the surface under the cumulative ranking
(SUCRA) curve method. We present ranking approaches' merits and limitations and
provide an example of how to apply the results of a NMA to clinical practice.
PMID- 28403894
TI - Antibiotic resistant airborne bacteria and their multidrug resistance pattern at
University teaching referral Hospital in South Ethiopia.
AB - BACKGROUND: Hospitals provide a reservoir of microorganisms, many of which are
multi-resistant to antibiotics. Emergence of multi-drug resistant strains in a
hospital environment, particularly in developing countries is an increasing
problem to infection treatment. This study aims at assessing antibiotic resistant
airborne bacterial isolates. METHODS: A cross-sectional study was conducted at
Wolaita Sodo university teaching and referral Hospital. Indoor air samples were
collected by using passive air sampling method. Sample processing and
antimicrobial susceptibility testing were done following standard bacteriological
techniques. The data was analyzed using SPSS version 20. RESULTS: Medically
important bacterial pathogens, Coagulase negative staphylococci (29.6%),
Staphylococcus aureus (26.3%), Enterococci species, Enterococcus faecalis and
Enterococcus faecium (16.5%), Acinetobacter species (9.5%), Escherichia coli
(5.8%) and Pseudomonas aeruginosa (5.3%) were isolated. Antibiotic resistance
rate ranging from 7.5 to 87.5% was detected for all isolates. Acinetobacter
species showed a high rate of resistance for trimethoprim-sulfamethoxazole,
gentamicin (78.2%) and ciprofloxacin (82.6%), 28 (38.9%) of S. aureus isolates
were meticillin resistant, and 7.5% Enterococci isolates of were vancomycin
resistant. 75.3% of all bacterial pathogen were multi-drug resistant. Among them,
74.6% were gram positive and 84% were gram negative. Multi-drug resistance were
observed among 84.6% of P. aeruginosa, of 82.5% Enterococcii, E. coli 78.6%, S.
aureus 76.6%, and Coagulase negative staphylococci of 73.6%. CONCLUSIONS: Indoor
environment of the hospital was contaminated with airborne microbiotas, which are
common cause of post-surgical site infection in the study area. Bacterial
isolates were highly resistant to commonly used antibiotics with high multi-drug
resistance percentage. So air quality of hospital environment, in restricted
settings deserves attention, and requires long-term surveillance to protect both
patients and healthcare workers.
PMID- 28403895
TI - Electroacupuncture for insomnia disorder: study protocol for a randomized
controlled trial.
AB - BACKGROUND: Insomnia is a common sleep disorder that affects many adults either
transiently or chronically. The societal cost of insomnia is on the rise, while
long-term use of current drug treatments can involve adverse effects. Recently,
electroacupuncture (EA) has been used to treat various conditions including
insomnia. The objective of this study is to provide scientific evidence for the
effect and safety of using EA to treat insomnia. METHODS/DESIGN: In this
multicentre, assessor-blind, three-arm, parallel-design, randomised controlled
trial, 150 participants will be assigned to the EA group, the sham EA (SEA)
group, or the usual care group. The EA and SEA groups will receive the specific
treatments 2-3 times a week for 4 weeks, for a total of 10 sessions, whereas the
usual care group will not receive EA and will continue with usual care during the
same time period. The primary outcome measure will be changes in the Insomnia
Severity Index 5 weeks after randomisation. The secondary outcomes will include
the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, a
sleep diary, the EuroQoL-5 dimension questionnaire, the levels of melatonin and
cortisol, and the Patient Global Impression of Change. Safety will be assessed at
each visit. DISCUSSION: The results of this multicentre randomised controlled
trial will contribute to provide rigorous clinical evidence for the effects and
safety of EA for insomnia disorder. TRIAL REGISTRATION: Korean Clinical Trial
Registry, CRIS, KCT0001685 . Registered on 2 November 2015 (retrospectively
registered). Date of enrolment of the first participant to the trial 13 October
2015.
PMID- 28403896
TI - Gas fermentation: cellular engineering possibilities and scale up.
AB - Low carbon fuels and chemicals can be sourced from renewable materials such as
biomass or from industrial and municipal waste streams. Gasification of these
materials allows all of the carbon to become available for product generation, a
clear advantage over partial biomass conversion into fermentable sugars.
Gasification results into a synthesis stream (syngas) containing carbon monoxide
(CO), carbon dioxide (CO2), hydrogen (H2) and nitrogen (N2). Autotrophy-the
ability to fix carbon such as CO2 is present in all domains of life but
photosynthesis alone is not keeping up with anthropogenic CO2 output. One
strategy is to curtail the gaseous atmospheric release by developing waste and
syngas conversion technologies. Historically microorganisms have contributed to
major, albeit slow, atmospheric composition changes. The current status and
future potential of anaerobic gas-fermenting bacteria with special focus on
acetogens are the focus of this review.
PMID- 28403897
TI - Trypanosoma vivax is the second leading cause of camel trypanosomosis in Sudan
after Trypanosoma evansi.
AB - BACKGROUND: This study was conducted in response to recurring reports from
eastern Sudan of camel trypanosomosis that can no longer be treated by currently
available trypanocidal drugs. One hundred and eighty-nine blood samples were
obtained from camels in different herds and local markets in the western part of
Sudan, and a cross-sectional study was carried out between December 2015 and
February 2016 to identify the causative agents and possible circulating
genotypes. RESULTS: The prevalence of trypanosomes detected using the
conventional parasitological techniques of Giemsa-stained blood smears, wet blood
smears and the microhematocrit centrifugation technique (MHCT) was 7% (13/189),
11% (21/189) and 19% (36/189), respectively. However, a multi-species KIN-PCR
targeting the ITS region revealed that the prevalence of Trypanosoma evansi was
37% (70/189), while that of T. vivax was 25% (47/189). Consequently, we used a T.
evansi-specific PCR (RoTat1.2 VSG gene) to analyse the KIN-PCR-positive samples
and a T. vivax-specific PCR (Cathepsin L-like gene) to analyse all of the
samples. The prevalence of T. evansi was 59% (41/70), while the prevalence of T.
vivax was 31% (59/189). Mixed infections were detected in 18% (34/189) of the
samples. These results were further confirmed by sequencing and a phylogenetic
analysis of the complete internal transcribed spacer (ITS) region of T. evansi
and the TviCatL gene of T. vivax. CONCLUSION: We conclude that T. vivax was newly
introduced to the camel population and that T. evansi is no longer the single
cause of camel trypanosomosis in Sudan. The presence of T. vivax in camels
detected in this study is a challenge in the choice of diagnostic approaches,
particularly serology, and PCRs. However, an analysis of drug resistance should
be performed, and the genotypic variation should be verified. To our knowledge,
this is the first molecular study on T. vivax and mixed-infection with T. vivax
and T. evansi in Sudanese camels.
PMID- 28403898
TI - Health risks associated with the pharmaceuticals in wastewater.
AB - The overwhelming population growth in recent decades and water crisis along with
limited and uneven geographical distribution of fresh water resources is a
growing challenge for the economic and human development. Wastewater reclamation
and use could be an alternative for intact water sources and a promising solution
to water scarcity and unequal distribution. However, wastewater is a double-edged
resource both as an accessible water source for food production and human usage
and concurrently may carry uncharacterized content with unknown toxicological
profile causing acute or long-term health risks. Pharmaceuticals, cosmeceuticals,
nanomaterials and their chemical decomposition derivatives found in wastewater
are not well known in many cases. Their unknown toxicity, teratogenicity and
carcinogenicity profile associated with lack of monitoring and control measures
impose a significant hazard risk on the public health. This paper reviews the
evidence on the health risks associated with the wastewater use for irrigated
food production and the imposed risk on the end consumers mainly from
pharmaceutical industry and related research facilities. Then, we suggest an
applied framework for planning and policy-making to mitigate the health risks and
optimally employ reclaimed wastewater for human purposes.
PMID- 28403899
TI - Hepato-bronchial fistula secondary to perforated sigmoid diverticulitis: a case
report.
AB - BACKGROUND: Patients with diverticulitis are predisposed to hepatic abscesses via
seeding through the portal circulation. Hepatic abscesses are well-documented
sequelae of diverticulitis, however instances of progression to hepato-bronchial
fistulization are rare. We present a case of diverticulitis associated with
hepatic abscess leading to hepato-bronchial fistulization, which represents a
novel disease course not yet reported in the literature. CASE PRESENTATION: A 61
year-old Caucasian man presented with a history of unintentional weight loss and
dyspnea both at rest and with exertion. He had a significant tobacco and alcohol
misuse history. A massive right-sided pleural effusion was found on chest X-ray,
which responded partially to chest tube insertion. A computed tomography scan of
his thorax confirmed the presence of innumerable lung abscesses as well as a
complex pleural effusion. An indeterminate tiny air pocket at the dome of the
liver was also noted. A follow-up computed tomography scan of his abdomen
revealed a decompressed hepatic abscess extending into the right pleural space
and the right lower lobe. A sigmoid-rectal fistula was also revealed with focal
colonic thickening, presumed to be the sequelae of remote or chronic
diverticulitis. An interventional radiologist inserted a percutaneous drain into
the decompressed hepatic abscess and the instillation of contrast revealed
immediate filling of the right pleural space, lung parenchyma, and bronchial
tree, confirming a hepato-bronchial fistula. After two concurrent chest tube
insertions failed to drain the remaining pleural effusion completely, surgical
lung decortication was conducted. Markedly thickened pleura were seen and a
significant amount of gelatinous inflammatory material was debrided from the
lower thoracic cavity. He recovered well and was discharged 10 days post
thoracotomy on oral antibiotics. The percutaneous liver abscess tube was removed
3 weeks post-discharge from hospital after the drain check revealed that the
fistula and abscess had entirely resolved. CONCLUSIONS: Refractory right-sided
pleural effusion combined with constitutional symptoms should alert clinicians to
search for possible hepatic abscess, especially in the context of diverticulitis.
The rupture of an untreated hepatic abscess could lead to death from profound
sepsis or rarely, as in this case, a hepato-bronchial fistula. Timely
investigation and a multidisciplinary treatment approach can lead to improved
patient outcomes.
PMID- 28403900
TI - Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteosarcoma
cells and induced apoptosis in vitro.
AB - BACKGROUND: Ubiquitin specific peptidase 39 (USP39), an essential factor in the
assembly of the mature spliceosome complex, has an aberrant expression in several
cancer. However, its function and the corresponding mechanism on human
osteosarcoma has not been fully explored yet. METHODS: The mRNA and DNA copies of
USP39 were increased in osteosarcoma cancer tissues compared with the one in
human normal tissues according to datasets from the publicly available Oncomine
database. A further western blot analysis also demonstrated an aberrant
endogenous expression of USP39 in three different osteosarcoma cells. Then
lentivirus-mediated short hairpin RNA (shRNA) was designed to silence USP39 in
human osteosarcoma cell line U2OS, which is used to test the impact of USP39
silencing on cellular proliferation, colony formation, cell cycle distribution
and apoptosis. RESULTS: Knockdown of USP39 expression in U2OS cell significantly
decreased cell proliferation, impaired colony formation ability. A further
analysis indicated suppression of USP39 arrested cell cycle progression at G2/M
phase via p21 dependent way. In addition, the results of Annexin V/7-AAD staining
suggested the knockdown of USP39 could promote U2OS cell apoptosis through PARP
cleavage. CONCLUSIONS: These results uncover the critical role of USP39 in
regulating cancer cell mitosis and indicate USP39 is critical for osteosarcoma
tumorigenesis.
PMID- 28403903
TI - Feasibility and safety of whole-body vibration therapy in intensive care
patients.
PMID- 28403902
TI - Phylodynamics of foot-and-mouth disease virus O/PanAsia in Vietnam 2010-2014.
AB - Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays
an important role in livestock trade within Southeast Asia. The large populations
of FMDV-susceptible species in Vietnam are important components of food
production and of the national livelihood. In this study, we investigated the
phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus' ancestral host
species (pig, cattle or buffalo), clinical stage (subclinical carrier or
clinically affected) and geographical location. Phylogenetic divergence time
estimation and character state reconstruction analyses suggest that movement of
viruses between species differ. While inferred transmissions from cattle to
buffalo and pigs and from pigs to cattle are well supported, transmission from
buffalo to other species, and from pigs to buffalo may be less frequent.
Geographical movements of FMDV O/PanAsia virus appears to occur in all directions
within the country, with the South Central Coast and the Northeast regions
playing a more important role in FMDV O/PanAsia spread. Genetic selection of
variants with changes at specific sites within FMDV VP1 coding region was
different depending on host groups analyzed. The overall ratio of non-synonymous
to synonymous nucleotide changes was greater in pigs compared to cattle and
buffalo, whereas a higher number of individual amino acid sites under positive
selection were detected in persistently infected, subclinical animals compared to
viruses collected from clinically diseased animals. These results provide novel
insights to understand FMDV evolution and its association with viral spread
within endemic countries. These findings may support animal health organizations
in their endeavor to design animal disease control strategies in response to
outbreaks.
PMID- 28403901
TI - CD44 and its ligand hyaluronan as potential biomarkers in malignant pleural
mesothelioma: evidence and perspectives.
AB - Malignant pleural mesothelioma (MPM) is a rare and highly drug resistant tumor
arising from the mesothelial surfaces of the lung pleura. The standard method to
confirm MPM is the tedious, time-consuming cytological examination of cancer
biopsy. Biomarkers that are detectable in pleural effusion or patient serum are
reasonable options to provide a faster and noninvasive diagnostic approach. As
yet, the current biomarkers for MPM lack specificity and sensitivity to
discriminate this neoplasm from other lung tumors. CD44, a multifunctional
surface receptor has been implicated in tumor progression in different cancers
including MPM. The interaction of CD44 with its ligand, hyaluronan (HA) has
demonstrated an important role in modulating cell proliferation and invasiveness
in MPM. In particular, the high expression levels of these molecules have shown
diagnostic relevance in MPM. This review will summarize the biology and
diagnostic implication of CD44 and HA as well as the interaction of both
molecules in MPM that will demonstrate their potential as biomarkers.
Augmentation of the current markers in MPM may lead to an earlier diagnosis and
management of this disease.
PMID- 28403904
TI - Pre-existing chronic interstitial pneumonia is a poor prognostic factor of
Goodpasture's syndrome: a case report and review of the literature.
AB - BACKGROUND: Goodpasture's syndrome is a rare disease that is characterized by
rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. CASE
PRESENTATION: A 71-year-old Japanese man who had chronic interstitial pneumonia
was diagnosed as having Goodpasture's syndrome. Both anti-glomerular basement
membrane antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody were
increased. Despite intensive treatments, including mechanical ventilation, he
died from respiratory failure. Pathological findings at autopsy showed rapidly
progressive glomerulonephritis in his kidneys, diffuse alveolar hemorrhage,
hyaline membranes, and fibroblastic foci in his lungs. The cause of death was
diagnosed as respiratory failure as a result of diffuse alveolar damage induced
by a combination of diffuse alveolar hemorrhage and exacerbation of interstitial
pneumonia. CONCLUSIONS: We report a case of Goodpasture's syndrome complicated
with pre-existing chronic interstitial pneumonia and positive myeloperoxidase
anti-neutrophil cytoplasmic antibody. We reviewed six similar cases reported in
the literature and concluded that Goodpasture's syndrome with pre-existing
interstitial pneumonia and myeloperoxidase anti-neutrophil cytoplasmic antibody
is related to a poor prognosis.
PMID- 28403906
TI - An additional k-means clustering step improves the biological features of WGCNA
gene co-expression networks.
AB - BACKGROUND: Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used
R software package for the generation of gene co-expression networks (GCN). WGCNA
generates both a GCN and a derived partitioning of clusters of genes (modules).
We propose k-means clustering as an additional processing step to conventional
WGCNA, which we have implemented in the R package km2gcn (k-means to gene co
expression network, https://github.com/juanbot/km2gcn ). RESULTS: We assessed our
method on networks created from UKBEC data (10 different human brain tissues), on
networks created from GTEx data (42 human tissues, including 13 brain tissues),
and on simulated networks derived from GTEx data. We observed substantially
improved module properties, including: (1) few or zero misplaced genes; (2)
increased counts of replicable clusters in alternate tissues (x3.1 on average);
(3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved
cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate
partitions in simulated data according to a range of similarity indices.
CONCLUSIONS: The results obtained from our investigations indicate that our k
means method, applied as an adjunct to standard WGCNA, results in better network
partitions. These improved partitions enable more fruitful downstream analyses,
as gene modules are more biologically meaningful.
PMID- 28403905
TI - H2A monoubiquitination in Arabidopsis thaliana is generally independent of LHP1
and PRC2 activity.
AB - BACKGROUND: Polycomb group complexes PRC1 and PRC2 repress gene expression at the
chromatin level in eukaryotes. The classic recruitment model of Polycomb group
complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A
monoubiquitination was recently challenged by data showing that PRC1 activity can
also recruit PRC2. However, the prevalence of these two mechanisms is unknown,
especially in plants as H2AK121ub marks were examined at only a handful of
Polycomb group targets. RESULTS: By using genome-wide analyses, we show that
H2AK121ub marks are surprisingly widespread in Arabidopsis thaliana, often co
localizing with H3K27me3 but also occupying a set of transcriptionally active
genes devoid of H3K27me3. Furthermore, by profiling H2AK121ub and H3K27me3 marks
in atbmi1a/b/c, clf/swn, and lhp1 mutants we found that PRC2 activity is not
required for H2AK121ub marking at most genes. In contrast, loss of AtBMI1
function impacts the incorporation of H3K27me3 marks at most Polycomb group
targets. CONCLUSIONS: Our findings show the relationship between H2AK121ub and
H3K27me3 marks across the A. thaliana genome and unveil that ubiquitination by
PRC1 is largely independent of PRC2 activity in plants, while the inverse is true
for H3K27 trimethylation.
PMID- 28403907
TI - Platypnea-orthodeoxia syndrome in the right lateral decubitus position: a case
report.
AB - BACKGROUND: Platypnea-orthodeoxia syndrome is a rare syndrome characterized by
dyspnea and hypoxia when the patient is sitting or standing. Here we report a
case of platypnea-orthodeoxia syndrome caused by a right hemidiaphragmatic
elevation with giant liver cyst that triggered a right-to-left shunt through the
patent foramen ovale. This case report is the first presentation of a case
secondary to hemidiaphragmatic elevation with giant liver cyst. In addition to
this, a malposition of the pacemaker lead could be associated with platypnea
orthodeoxia syndrome in this case. CASE PRESENTATION: A 91-year-old Japanese
woman presented to our hospital with hypoxia of unknown origin. Severe hypoxia
and cyanosis were observed only in the right lateral decubitus position. A chest
X-ray and computed tomography scan revealed right hemidiaphragmatic elevation,
which was probably compressing the right atrium. A transesophageal echocardiogram
showed a compressed right atrium and shunt blood flow in both directions: from
the left to the right atrium and vice versa. The shunt flow was exacerbated by
postural changes from the left to the right lateral decubitus. A transesophageal
echocardiogram also confirmed compression of the right atrium due to giant liver
cyst and a malposition of the pacemaker lead abnormally placed in the left atrium
through patent foramen ovale. We concluded that the cause of hypoxia was
platypnea-orthodeoxia syndrome with right-to-left interatrial shunt through
patent foramen ovale. Surgical closure of patent foramen ovale was not performed
due to the age of our patient, surgical difficulties, and failure to obtain
informed consent. For these reasons she was discharged after receiving medical
advice about her posture. CONCLUSIONS: Platypnea-orthodeoxia syndrome is rare and
difficult to diagnose. The present case suggests that hypoxia due to postural
changes should be considered a differential diagnosis of platypnea-orthodeoxia
syndrome.
PMID- 28403908
TI - Permissiveness of bovine epithelial cells from lung, intestine, placenta and
udder for infection with Coxiella burnetii.
AB - Ruminants are the main source of human infections with the obligate intracellular
bacterium Coxiella (C.) burnetii. Infected animals shed high numbers of C.
burnetii by milk, feces, and birth products. In goats, shedding by the latter
route coincides with C. burnetii replication in epithelial (trophoblast) cells of
the placenta, which led us to hypothesize that epithelial cells are generally
implicated in replication and shedding of C. burnetii. We therefore aimed at
analyzing the interactions of C. burnetii with epithelial cells of the bovine
host (1) at the entry site (lung epithelium) which govern host immune responses
and (2) in epithelial cells of gut, udder and placenta decisive for the quantity
of pathogen excretion. Epithelial cell lines [PS (udder), FKD-R 971 (small
intestine), BCEC (maternal placenta), F3 (fetal placenta), BEL-26 (lung)] were
inoculated with C. burnetii strains Nine Mile I (NMI) and NMII at different
cultivation conditions. The cell lines exhibited different permissiveness for C.
burnetii. While maintaining cell viability, udder cells allowed the highest
replication rates with formation of large cell-filling Coxiella containing
vacuoles. Intestinal cells showed an enhanced susceptibility to invasion but
supported C. burnetii replication only at intermediate levels. Lung and placental
cells also internalized the bacteria but in strikingly smaller numbers. In any of
the epithelial cells, both Coxiella strains failed to trigger a substantial IL
1beta, IL-6 and TNF-alpha response. Epithelial cells, with mammary epithelial
cells in particular, may therefore serve as a niche for C. burnetii replication
in vivo without alerting the host's immune response.
PMID- 28403909
TI - Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a
"two-hit" model.
AB - Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause
of mortality and long-term neurologic disability in survivors. The
pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in
secondary brain injury and neuronal cell death. This begins with primary injury
to the brain caused by the immediate cessation of cerebral blood flow following
CA. Thereafter, the secondary injury of HIBI takes place in the hours and days
following the initial CA and reperfusion. Among factors that may be implicated in
this secondary injury include reperfusion injury, microcirculatory dysfunction,
impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia,
fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the
underlying pathophysiology of HIBI is imperative and has been the focus of
considerable research to identify therapeutic targets. Most notably, targeted
temperature management has been studied rigorously in preventing secondary injury
after HIBI and is associated with improved outcome compared with hyperthermia.
Recent advances point to important roles of anemia, carbon dioxide perturbations,
hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury
after HIBI and adverse outcomes. Furthermore, breakthroughs in the
individualization of perfusion targets for patients with HIBI using cerebral
autoregulation monitoring represent an attractive area of future work with
therapeutic implications.We provide an in-depth review of the pathophysiology of
HIBI to critically evaluate current approaches for the early treatment of HIBI
secondary to CA. Potential therapeutic targets and future research directions are
summarized.
PMID- 28403910
TI - Topical application of Jaungo in atopic dermatitis patients: study protocol for a
randomized, controlled trial.
AB - BACKGROUND: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease
with increasing prevalence. It can manifest with many different clinical
phenotypes; however, in its chronic stage, hyperpigmentation, excoriation,
lichenification, and dryness are the main symptoms. Jaungo comprises two herbs,
Lithospermi radix and Angelica gigantis radix, and three carrier oils, and is an
approved herbal ointment for xerosis cutis in Korea. In past studies, we
demonstrated that Jaungo had anti-inflammatory and antiallergic activity in in
vitro and in vivo AD models; however, there are few relevant randomized
controlled clinical trials on Jaungo in AD. METHODS/DESIGN: A randomized, double
blind, placebo-controlled, single-center, phase IIa clinical trial was designed
to investigate the safety, preliminary efficacy, and dose response of Jaungo in
AD. The study protocol was approved by the Institutional Review Boards of the
Kyung Hee University Korean Medicine Hospital (No. KOMCIRB-160617-HR-027) and the
Korea Food and Drug Administration (No. 30907). The study aims to enroll 34 AD
patients to be randomly distributed among three parallel groups: treatment 1,
treatment 2, and the placebo group. Treatment group 1 applies Jaungo twice a day,
while treatment group 2 applies Jaungo and the placebo ointment once a day,
separately, and the placebo group applies the placebo ointment twice a day, for a
total of 3 weeks each. Participants will be evaluated for eczema before and after
the application of the ointments based on several parameters including the Eczema
Area and Severity Index, the SCORing of Atopic Dermatitis Index, the Dermatology
Life Quality Index, transepidermal water loss, total IgE level, eosinophil count,
and IL-17, IL-22, and IFN-gamma levels. DISCUSSION: The trial is currently
ongoing and the enrollment of subjects has been initiated. There is an urgent
need to develop a drug for the treatment of dry, hyperpigmented, scaly, and
thickened skin in chronic-stage AD. This study will determine the efficacy and
safety of Jaungo in AD, providing evidence for specific AD symptoms treated by
Jaungo. TRIAL REGISTRATION: Clinical Trials.gov, identifier: NCT02900131 .
Registered on 2 September 2016. Korea Clinical Research Information Service,
identifier: KCT0002060 . Registered on 22 July 2016.
PMID- 28403912
TI - Recent Progress in Cell Therapy and Regenerative Medicine for Neurological
Disorders: Introduction to the ASNTR Special Issue From the 2016 Meeting.
PMID- 28403911
TI - PREDOMOS study, impact of a social intervention program for socially isolated
elderly cancer patients: study protocol for a randomized controlled trial.
AB - BACKGROUND: Cancer incidence and social isolation increase along with advanced
age, and social isolation potentiates the relative risk of death by cancer. Once
spotted, social isolation can be averted with the intervention of a
multidisciplinary team. Techniques of automation and remote assistance have
already demonstrated their positive impact on falls prevention and quality of
life (QoL), though little is known about their impact on socially isolated
elderly patients supported for cancer. The primary objective of the PREDOMOS
study is to evaluate the impact of establishing a Program of Social intervention
associated with techniques of Domotic and Remote assistance (PS-DR) on the
improvement of QoL of elderly isolated patients, treated for locally advanced or
metastatic cancer. The secondary objectives include treatment failure, tolerance,
survival, and autonomy. METHODS/DESIGN: This trial is a multicenter, prospective,
randomized, placebo-controlled, open-label, two-parallel group study. The setting
is 10 French oncogeriatric centers. Inclusion criteria are patients aged at least
70 years with a social isolation risk and a histological diagnosis of cancer,
locally advanced or metastatic disease. The groups are (1) the control group,
receiving usual care; (2) the experimental group, receiving usual care
associating with monthly social assistance, domotic, and remote assistance.
Participants are randomized in a 1:1 allocation ratio. Evaluation times involve
inclusion (randomization) and follow-up (12 months). The primary endpoint is QoL
at 3 months (via European Organization for Research and Treatment of Cancer
(EORTC) QLQ C30); secondary endpoints are social isolation, time to treatment
failure, toxicity, dose response-intensity, survival, autonomy, and QoL at 6
months. For the sample size, 320 individuals are required to obtain 90% power to
detect a 10-point difference (standard deviation 25) in QoL score between the two
groups (20% loss to follow-up patients expected). DISCUSSION: The randomized
controlled design is the most appropriate design to demonstrate the efficacy of a
new experimental strategy (Evidence-Based Medicine Working Group classification).
National and international recommendations could be updated based on the findings
of this study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02829762 . Registered
on 29 June 2016.
PMID- 28403913
TI - Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian
Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease.
AB - Parkinson's disease (PD) is a neurodegenerative disorder, characterized by the
loss of dopaminergic neurons in the substantia nigra and their projections to the
striatum. Several processes have been described as potential inducers of the
dopaminergic neuron death, such as inflammation, oxidative stress, and
mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be
multifactorial, and its cause remains unclear. ATP-activating purinergic
receptors influence various physiological functions in the CNS, including
neurotransmission. Purinergic signaling is also involved in pathological
scenarios, where ATP is extensively released and promotes sustained purinergic
P2X7 receptor (P2X7R) activation and consequent induction of cell death. This
effect occurs, among other factors, by oxidative stress and during the
inflammatory response. On the other hand, peroxisome proliferator-activated
receptor-gamma coactivator 1alpha (PGC-1alpha) is involved in energy metabolism
and mitochondrial biogenesis. Expression and activity upregulation of this
protein has been related with reduction of oxidative stress and neuroprotection.
Therefore, P2X7R and PGC-1alpha are potential targets in the treatment of PD.
Here hemiparkinsonism was induced by unilateral stereotactic injection of 6-OHDA
in a rat model. After 7 days, the establishment of PD was confirmed and followed
by treatment with the P2X7R antagonist Brilliant Blue G (BBG) or PGC-1alpha
agonist fenofibrate. BBG, but not fenofibrate, reverted hemiparkinsonian behavior
accompanied by an increase in tyrosine hydroxylase immunoreactivity in the
substantia nigra. Our results suggest that the P2X7R may be a therapeutic target
in Parkinson's disease.
PMID- 28403914
TI - Are primary healthcare services culturally appropriate for Aboriginal people?
Findings from a remote community.
AB - This study explored the views of key stakeholders on cultural appropriateness of
primary health care (PHC) services for Aboriginal people. A total of 78
participants, including healthcare providers, administrative team members (n=24,
~30% of study sample) and Aboriginal community members (n=54, ~70% of study
sample) living in remote North West Queensland participated in the study. Outcome
measures were assessed by administering survey questionnaires comprising
qualitative questions and various subscales (e.g. provider behaviours and
attitudes, communication, physical environment and facilities, and support from
administrative staff). Descriptive statistics were used to present quantitative
findings, whereas inductive thematic analysis was used for qualitative data. In
contrast to the views of PHC providers, a significant number of Aboriginal people
did not perceive that they were receiving culturally appropriate services.
Although PHC providers acknowledged cultural awareness training for familiarising
themselves with Aboriginal culture, they found the training to be general,
superficial and lacking prospective evaluation. PHC providers should understand
that culturally inappropriate clinical encounters generate mistrust and
dissatisfaction. Therefore, a broad approach involving culturally respectful
association between PHC providers, Aboriginal consumers and administrative staff
is required to bring sustainable changes at the practice level to improve the
health of Aboriginal people.
PMID- 28403915
TI - The egg coat zona pellucida 3 glycoprotein - evolution of its putative sperm
binding region in Old World murine rodents (Rodentia: Muridae).
AB - In eutherian mammals, before fertilisation can occur the spermatozoon has to bind
to, and penetrate, the egg coat, the zona pellucida (ZP). In the laboratory mouse
there is good evidence that the primary sperm-binding site is a protein region
encoded by Exon 7 of the ZP3 gene and it has been proposed that binding is
species specific and evolves by sexual selection. In the present study we
investigate these hypotheses by comparing Exon 6 and 7 sequences of ZP3 in 28
species of murine rodents of eight different divisions from Asia, Africa and
Australasia, in which a diverse array of sperm morphologies occurs. We found
considerable nucleotide (and corresponding amino acid) sequence divergence in
Exon 7, but not in Exon 6, across these species, with evidence for positive
selection at five codon positions. This molecular divergence does not appear to
be due to reinforcement to reduce hybridisation, nor does it correlate with
divergence in sperm head morphology or tail length, thus it is unlikely to be
driven by inter-male sperm competition. Other forms of post-copulatory sexual
selection therefore appear to have resulted in the molecular divergence of this
region of ZP3 in this highly speciose group of mammals.
PMID- 28403916
TI - [Conservative management of endometrioma in women undergoing in vitro
fertilization].
AB - Endometriosis is a chronic disease. The pathogenesis is actually still unclear.
Endometriosis is responsible for infertility and/or pelvic pain. One of the most
important features of the disease is the heterogeneity (clinical and anatomical).
Among the different phenotypes of endometriosis, the ovarian endometrioma seems
to most important lesion in the management of endometriosis-related infertility.
Surgical treatment is associated to a decrease of the ovarian reserve and a
potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the
choice between conservative or surgical management of endometrioma before IVF is
actually debated. The advantages and drawback of surgical and conservative
management should be discussed before to plan the treatment. In the present
review, we aimed at assessing the risks of a conservative management of
endometrioma as compared to surgery before IVF.
PMID- 28403917
TI - [Contraception during perimenopause: The spermicides option].
AB - AIM: In perimenopause, the increased cardiovascular and cancer risk and the
increased incidence of gynaecologic disorders have a major impact on the choice
of an appropriate contraceptive method. The aim of this review is to assess the
potential benefit of spermicides at this stage of woman's life. MATERIALS AND
METHODS: This review presents the eligibility criteria of the different
contraceptive methods according to national and international guidelines,
together with a literature review of the efficacy and side-effects of the two
major spermicidal preparations, benzalkonium chloride and nonoxynol-9, with
specific focus on the over-40 age group. RESULTS: The guidelines do not
contraindicate any contraceptive method in women after 40. The efficacy data of
spermicides show high variation between publications, with no age-specific
differences. A special group suitable for spermicide use for contraception is
perimenopausal women, particularly those with contraindications to other
contraceptive methods or unwilling to use them. An additional benefit of some
spermicides could be their lubricant effect. CONCLUSION: The spermicide option
should be included into contraceptive counselling for women aged over 40, with
evidence-based information about their mechanism of action, efficacy and safety.
There is, however, a need for efficacy and acceptability studies on spermicides,
with special reference to this age group.
PMID- 28403918
TI - Trauma and endometriosis. A review. May we explain surgical phenotypes and
natural history of the disease?
AB - OBJECTIVE: The study was performed to evaluate whether trauma is an initial event
of development of endometriosis. METHOD: Using Medline database from January 1960
up to December 2014, a systematic review was made of all published studies using
the keywords trauma, healing, injury, infection, hyperperistaltism, stretch and
endometriosis, adenomyosis and trauma. Studies and review articles written in
French and/or in English related to the topic were included and reviewed
independently by two authors. RESULTS: The role of trauma is well-established for
endometriotic lesions diagnosed in surgical scars. Various traumas including
delivery, uterine curettage or incision, intraperitoneal hemorrhage, or occult
pelvic inflammatory diseases could be involved to explain other localizations of
the disease. Many data suggested that the healing process, particularly growth
factors and the associated estrogen production, may facilitate the implantation
and the growth of ectopic endometrial cells. After the initial, a traumatic
event, the phenotype of the disease would depend on the tissue in which the
endometriotic lesion grows. CONCLUSIONS: The present literature review may
support a potential role of a trauma as an initial event of endometriosis.
PMID- 28403919
TI - Ureterovesical reimplantation for ureteral deep infiltrating endometriosis: A
retrospective study.
AB - INTRODUCTION AND HYPOTHESIS: Symptoms of endometriosis of the urinary tract
consist of nonspecific signs that are often trivialized. However, late diagnosis
may be responsible for an upstream impact. The aim of this study is to describe a
population of patients who received ureterovesical reimplantation for deep
infiltrating endometriosis. We evaluate the preoperative clinical and
radiological symptoms and long-term surgical outcomes. METHODS: All the
endometriotic patients who underwent ureterovesical reimplantation at Lille
university hospital between 2003 and 2013 were included retrospectively. RESULTS:
Seventeen patients were included. Urological symptoms of endometriosis were
present in 53% of patients and 29% had a history of urological surgery. Delay
between diagnosis and ureteral reimplantation was 64+/-65 months on average.
Forty-seven percent of patients had urinary functional symptoms consisting mainly
of lower back pain. The ureteral lesion was known preoperatively and associated
with hydroureteronephrosis in 82% of cases. Thirty-five percent of patients had
renal atrophy and renal function was impaired in 23% of cases. Mean follow-up was
45+/-27 months. Forty-one percent of patients presented at least one immediate
postoperative complication-fistula, postoperative infection or nerve compression.
Also, urinary functional symptoms, dyspareunia and dysmenorrhea were maintained
in 47%. CONCLUSION: Ureterovesical reimplantation in a context of endometriosis
is major surgery with frequent complications. It requires close collaboration
between gynecologists, radiologists and urologists. Prior comprehensive patient
information is essential. Diagnosis and early treatment of ureteral endometriosis
lesions should help reduce the morbidity of this disease.
PMID- 28403920
TI - Psychometric properties of the French version of the Endometriosis Health Profile
30, a health-related quality of life instrument.
AB - INTRODUCTION: The objectives were to evaluate the acceptability, reliability and
validity of the cross-cultural adaptation of the Endometriosis Health Profile-30
instrument into French. METHODS: This cross-sectional study was conducted between
July and October 2015. We created an online link (REDCap platform) with the
questionnaires. An endometriosis patients association spread the link on its
website and with social networks. The translation and cultural adaptation of the
EHP-30 was performed according to guidelines. Psychometric evaluation included
data completeness, score distributions, floor and ceiling effects, factor
analysis, internal consistency, item-total correlations corrected for overlap,
convergent validity and test-retest reliability. RESULTS: The study included 913
women with endometriosis. In our results, data completeness was excellent. No
floor effects were found and one ceiling effect was observed for the
'Infertility' scale. The highest means scores were found for 'Control and
powerlessness' and 'Infertility' scales. Factor analysis confirmed the structure
of the original EHP-30 questionnaire. Internal consistency was good (Cronbach's
alpha range=0.72-0.96). The correlations of similar scale scores between EHP-30
and SF-36 were all significant (Spearman correlation coefficients ranging from
0.52 to -0.75). Test-retest reliability was good (intraclass correlation
coefficients range=0.51-0.98). CONCLUSION: The French version of the EHP-30 is an
acceptable, reliable and valid instrument for measuring health-related quality of
life in women with endometriosis.
PMID- 28403921
TI - Oxidative and antioxidative status in the endometrium of patients with benign
gynecological disorders.
AB - AIM: Oxidative stress and impaired antioxidative system are implicated in the
development of many disease states including gynecological diseases. In the
present study, we aimed to investigate the oxidative-antioxidative status in
endometrium of patients diagnosed with benign gynecological disorders. METHODS:
Samples of endometria and blood were obtained from 65 patients admitted to our
center for abnormal uterine bleeding or postmenopausal bleeding. Endometrial
biopsy was performed for the evaluation of histopathology and oxidative
antioxidative status in endometrial tissue. Based on histological examination,
subjects were divided into groups as follows: normal controls (n=15); patients
with endometrial polyps (n=20); patients with uterine myoma (n=10) patients with
chronic endometritis (n=10), and patients with atrophic endometrium (n=10).
Activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase
(GR) and total antioxidant status (TOS), total oxidant status (TAS) were
assessed. RESULTS: Compared to the normal controls, nonsignificant changes
(decrease or increase) were detected in antioxidant enzyme activities, TAS and
TOS in the examined groups. Additionally, between TAS and TOS, we also found a
strong positive correlation in normal and chronic endomethritis groups and a
moderate positive correlation uterine myoma, endometrial polyps and endometrial
atrophy groups. CONCLUSION: Even though, our results do not allow to conclude how
oxidative and antioxidative status are influenced in benign gynecological
disorders, these findings may provide a basis for the further researches.
PMID- 28403922
TI - Place of ulipristal acetate in the management of uterine fibroids: Preoperative
treatment or sequential treatment?
AB - Symptomatic uterine fibroids affect 25% of women of childbearing potential and
are responsible for various symptoms, mainly menometrorrhagia, pelvic pain and
infertility. No currently available medical treatment is able to eradicate
fibroids. Two treatments are indicated preoperatively to reduce bleeding and
decrease the size of fibroids: GnRH agonists and ulipristal acetate. Ulipristal
acetate, a selective progesterone receptor modulator, exerts an antagonist effect
on fibroid tissue, inducing apoptosis. It rapidly induces amenorrhoea (after an
average of seven days of treatment) and reduces fibroid volume. It causes few
adverse effects and, in particular, is associated with a low rate of hot flashes
compared to GnRH agonists. Due to its partial antagonist effect on endometrial
tissue, endometrial thickening with no glandulocystic atypia is commonly observed
during treatment and is reversible after stopping treatment. These specific
histological changes are called Progesterone receptor modulator-Associated
Endometrial Changes (PAEC). Since February 2012, ulipristal acetate has been
approved in Europe for preoperative treatment of symptomatic fibroids for two
three-month cycles. The use of ulipristal acetate facilitates surgery or allows
modification of the surgical approach (due to a reduction of fibroid volume) and
restores normal preoperative hemoglobin. In some cases, the reduction of
menometrorrhagia induced by treatment can allow surgery to be postponed. Since
May 2015, ulipristal acetate is also indicated as repeated sequential treatment
for moderate-to-severe symptoms due to uterine fibroids.
PMID- 28403923
TI - High abortion rate in Martinique (F.W.I.) in spite of a large contraceptive
availability. What are the determinants?
AB - INTRODUCTION: Despite a similar health insurance coverage and access to
contraception, Martinique F.W.I. has a higher rate of abortion than continental
France (25.6 versus 15.3 per thousand respectively). The reasons are still
largely unknown. A different contraceptive pattern, a lower use of emergency
contraception in Martinique may be involved. We sought to explore the
contraceptive pattern, to evaluate the use of emergency contraception and the
reasons leading to an unwanted pregnancy among women seeking for an abortion.
MATERIAL AND METHODS: An anonymous cross-sectional survey about the contraceptive
use in the year and in the month before abortion, the use of emergency
contraception and the reasons why, to patients' point of view, they became
pregnant albeit not willing it was proposed to women seeking for an abortion in
the dedicated unit of the university hospital of Martinique. RESULTS: Six hundred
patients were included. A total of 83.7% of patients declared having a regular
contraceptive use during the year preceding. Just before abortion, 61.1% of women
had no contraception or a low reliable method (fertility awareness,
withdrawal...). Lack of recognition of pregnancy risk was the main reason leading
to abortion, accounting for 51.1% of cases, explaining a low use of emergency
contraception (13.8%), whereas a difficult access to contraception was rarely
quoted. Emergency contraception was used in 27.8% of relevant situations.
CONCLUSION: Insufficient estimation of pregnancy risk is the main reason leading
to unwanted pregnancy. Availability of emergency contraception does not reduce
the risk.
PMID- 28403924
TI - [Parental project of general medicine residents from Aix-Marseille university:
Theoretical knowledge in reproduction and behavior towards parenting].
AB - OBJECTIVES: Analyze residents' intentions about parenting and knowledge about
fertility, as well as their alleged behavior towards a diagnosis of diminished
ovarian reserve. MATERIALS AND METHODS: Prospective study with distribution of
self-administered questionnaire to residents of Aix-Marseille university from
June to September 2015. The questionnaire was composed of a first descriptive
part including generic and personal informations about the residents and their
intentions towards parenting. The second part was a 9 questions survey aimed at
testing their knowledge about fertility and ovarian reserve and a final question
placing them in a situation of a diminished ovarian reserve diagnosis in order to
analyze their reactions. RESULTS: The overall participation rate was 53.2%,
including 220 women with an average age of 27 years (SD: 1.8 years) and 116 men
with an average age of 27.3 years (SD: 2.2 years). The 11.8% of female residents
(n=26) already had one or more children vs.6.9% of male residents (n=8). Among
the residents without children, 99% of females (n=192) and 91.7% of males (n=99)
said they wanted to have children in the future, planning an average age to have
their first child of 29.6 years (SD: 1.9 years) for females and 30.4 years (SD:
2.2 years) for men. Moreover, 58.3% of female residents (n=112) and 53.5% of male
residents (n=53) reported that they were postponing their plan to have children
after the completion of their medical studies. In a simulation of couples facing
a diagnosis of diminished ovarian reserve, 73.6% of females and 61.2% of males
would be ready to change their life choices and conceive a baby sooner than
originally planned. CONCLUSION: Almost all the general medicine residents have
plannedto have children in the future and more than half of them postpone their
parental plan after the end of their residency, although the decline of female
fertility in relation to aging is widely known among them.
PMID- 28403925
TI - Prevention of infertility induced by ovarian ischemia reperfusion injury by
benidipine in rats: Biochemical, gene expression, histopathological and
immunohistochemical evaluation.
AB - INTRODUCTION: Benidipine has been reported to prevent the ischemia/reperfusion
(I/R) damage in heart tissue and to suppress oxidant and proinflammatory cytokine
production, increased by I/R. However, There was no information about the effects
of benidipine on I/R injury in the ovary and the damage of I/R-induced
infertility. OBJECTIVES: The aim of the study was to investigate the effects of
benidipine on bilateral ovarian I/R injury and whether or not effective in the
treatment of I/R-induced infertility in rats. METHOD: Forty-eight females, albino
Wistar rats were randomly divided into 4 groups: IRC group (ovarian I/R group,
n=12), IRB-2 group (ovarian I/R+2mg/kg benidipine group, n=12), IRB-4 group
(ovarian I/R+4mg/kg benidipine group, n=12) and HG group (healthy group with sham
operation, n=12). In IRB-2 and IRB-4 groups, two hours ischemia and two hours
reperfusion was performed following orally benidipine administration. After this
I/R procedure, 6 rats from each group performed bilateral overectomy. Ovarian
levels of malondialdehyde (MDA) and total glutathione (tGSH), ovarian gene
expressions of interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF
alpha) and also apoptosis were evaluated. The other 6 rats from each group were
put in together with six male rats in separated cages for 2 months in order to
reproduce. During this period, rats which did not become pregnant were accepted
as infertile. RESULTS: MDA levels, expressions of TNF-alpha and IL-1beta in IRC
group were significantly higher than in the SGA group and tGSH was decreased. In
total, 4mg/kg benidipine has better prevented ovaries from the increase of
oxidants and proinflammatory cytokines, the decrease of antioxidants than 2mg/kg
benedipine. In the histopathological examination hemorrhage, congestion, follicle
degeneration, neutrophil infiltration and necrosis were seen in ovarian tissue of
IRC group. Only dilated and congested blood vessels were found in the IRB-2
group. No histopathological finding was encountered in the IRB-4 group. I/R
caused infertility in rats. In total, 4mg/kg benidipine prevented from
infertility better than the dose of 2mg/kg benedipine. CONCLUSION: In total,
4mg/kg benidipine reduced I/R injury and I/R-related infertility more
significantly compared to 2mg/kg benedipine in rat ovaries.
PMID- 28403926
TI - Prenatal microarray comparative genomic hybridization: Experience from the two
first years of activity at the Lyon university-hospital.
AB - OBJECTIVES: This study aims to describe how microarray comparative genomic
hybridization (aCGH) has shifted to become a prenatal diagnosis tool at the Lyon
university-hospital. MATERIALS AND METHODS: This retrospective study included all
patients who were referred in the 3 pluridisciplinary centers for prenatal
diagnosis of the Lyon university-hospital and who received a prenatal aCGH
between June 2013 and June 2015. aCGH was systematically performed in parallel
with a karyotype, using the PreCytoNEM array design. RESULTS: A total of 260
microarrays were performed for the following indications: 249 abnormal
ultrasounds (95.8%), 7 characterizations of chromosomal rearrangements (2.7%),
and 4 twins with no abnormal ultrasounds (1.5%). With a resolution of 1 mega
base, we found 235 normal results (90.4%), 23 abnormal results (8.8%) and 2 non
returns (0.8%). For the chromosomal rearrangements visible on the karyotype, aCGH
identified all of the 12 unbalanced rearrangements and did not identify the 2
balanced rearrangements. Among the fetuses with normal karyotypes, 11 showed
abnormal microarray results, corresponding to unbalanced cryptic chromosomal
rearrangements (4.2%). CONCLUSION: Transferring aCGH to a prenatal diagnosis at
the Lyon university-hospital has increased the detection rate of chromosomal
abnormalities by 4.2% compared to the single karyotype.
PMID- 28403927
TI - Relevance of routine Doppler sampling at the two umbilical arteries in the follow
up of dichorionic twin pregnancies with intrauterine growth-restricted fetuses.
AB - OBJECTIVE: The aim of this study is to assess if the presence of bilateral absent
or reverse end-diastolic velocity (AREDV) indicates a poorer prognosis than
unilateral AREDV in dichorionic-diamniotic twin pregnancies complicated by
intrauterine growth restriction. METHODS: A prospective observational study of 36
dichorionic-diamniotic twin pregnancies complicated by intrauterine growth
restriction. One hundred and fifty seven ultrasound (US) examinations were
performed. The pulsatility indexes (PI) of the two umbilical arteries (UA
perivesical site), the middle cerebral artery (MCA) and the ductus venosus (DV)
were recorded. The fetal hemodynamic status was represented by the existence of a
bilateral positive end-diastolic velocity (PEDV), a unilateral AREDV or a
bilateral AREDV in the umbilical arteries. RESULTS: Bilateral PEDV, unilateral
AREDV and bilateral AREDV represented respectively 66.0%, 10.6% and 23.4% of the
US examinations. Intervals between Doppler examinations and delivery were
significantly longer (P<0.005) in the bilateral PEDV group (26.5 days+/-19.7)
than in the unilateral AREDV group (11.8 days+/-11.7) and in the bilateral AREDV
group (11.0 days+/-8.6). MCA-PI, DV-PI, IFI and early neonatal outcomes did not
differ between the unilateral and bilateral AREDV groups. CONCLUSION: The routine
measurement of the Doppler indices of the two umbilical arteries seems to be no
more relevant than unilateral measurement in fetuses of dichorionic-diamniotic
twin pregnancies complicated by intrauterine growth restriction.
PMID- 28403928
TI - [Prenatal diagnosis of neural tube defects: Correlation between prenatal and
postnatal data].
AB - OBJECTIVES: Neural tube defects (NTD) are congenital anomalies that can cause
significant neurological long-term disabilities. Theses malformations are
accessible to prenatal diagnosis and quite recently, to in utero repair for some
myelomeningoceles. The aim of this study was to analyse the correlation between
prenatal and postnatal examinations. MATERIALS AND METHODS: A descriptive
retrospective monocentric study has been conducted between January 2004 and
December 2014 in a tertiary care maternity. All patients who benefited a prenatal
diagnosis of NTD for their foetus, and for whom postnatal data were available
were included. Prenatal and postnatal data, especially type of dysraphism, levels
of defect and extent, and associated anomalies were compared. RESULTS: Sixty
spinal dysraphisms were diagnosed antenataly. Concerning the type of dysraphism,
ultrasound diagnosis was well correlated with postnatal findings (rho=0.7048).
Prenatal level and extent were correlated with postnatal data (respectively
rho=0.539 and rho=0.562). Vertebral upper level defined by ultrasound agreed with
postnatal constatations in 80.8% of cases within one vertebra, and in 84.6% of
cases within two vertebras. Concerning indirect signs of spina bifida, prenatal
data agreed with postnatal ones for most of them, especially for Arnold Chiari II
malformation. CONCLUSION: There is a high correlation between prenatal and
postnatal data. Prenatal ultrasound seems to be efficient for description of
neural tube defects and to identify foetuses for which the benefit of in utero
surgery exists.
PMID- 28403929
TI - [Conservative placenta percreta management using uterine arterial embolization
procedure: A series of 12 cases].
AB - We report a retrospective series of 12 placentas percreta with bladder invasion
and for which an expected initially multidisciplinary conservative surgical
treatment associated with uterine artery embolization was programmed.
Conservative surgical treatment was only performed in 7 women. Radical surgical
treatment was necessary during the caesarean section and complicated by massive
hemorrhage in three women and secondary in two other women for infectious
diseases. Radical surgical treatment was associated with partial cystectomy
complicated with urinary disorder sequelae in three women. Maternal morbidity of
the placenta percreta bladder remains high despite the establishment of a
multidisciplinary care protocol.
PMID- 28403930
TI - Neonatal pancytopenia in a child, born after maternal exposure to natalizumab
throughout pregnancy.
AB - Natalizumab is a monoclonal antibody indicated for the treatment of patients with
relapsing-remitting multiple sclerosis. Its use is prohibited during pregnancy.
However, natalizumab exposures throughout the gestation period or during the
third trimester, because of intense disease activity, are possible and begin to
be reported. There are enough reassuring arguments against a teratogenicity,
through pregnancy registries; but deleterious effects in the monitoring of
newborn, are not well known. A disorder of hematopoiesis is possible with anemia,
thrombocytopenia or pancytopenia, as discussed by the author through an
observation. These hematological disorders seem to be asymptomatic; they resolve
spontaneously and require a simple biological and clinical monitoring of the
newborn.
PMID- 28403931
TI - Did the prophylactic salpingectomy might replace the tubal ligation?
PMID- 28403932
TI - Response to Dr Nohuz's letter: Could prophylactic salpingectomy replace tubal
ligation?
PMID- 28403933
TI - Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin
signaling/action, decreases adiposity and may alter anxiety behavior.
AB - OBJECTIVE: Protein tyrosine phosphatase 1B (PTP1B) has been extensively
implicated in the regulation of body weight, food intake, and energy expenditure.
The role of PTP1B appears to be cell and brain region dependent. RESULTS: Herein,
we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the
central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking
down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was
sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling
in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and
food intake and also increases energy expenditure, without altering ambulatory
activity. These changes were explained, at least in part, by the improvement of
insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression.
There was a slight decline in fasting blood glucose and serum insulin levels
possibly due to leanness in rats treated with ASO. Surprisingly, the elevated
plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the
CeA. CONCLUSIONS: Thus, the present study highlights the deleterious role that
the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of
PTP1B in the CeA may be a strategy for the treatment of obesity, insulin
resistance and anxiety disorders.
PMID- 28403934
TI - A synthetic Nitraria alkaloid, isonitramine protects pancreatic beta-cell and
attenuates postprandial hyperglycemia.
AB - OBJECTIVE: The extracts of Nitraria genus are composed of Nitraria alkaloids and
have been used traditionally as a hypoglycemic medicine. However, the efficacy
and precise mechanism of Nitraria alkaloids remain largely unknown. METHODS:
Previously, we reported the total synthesis of (+)-isonitramine, one of Nitraria
alkaloids. In this study, we investigated the anti-diabetic potential of
isonitramine in diabetes mellitus and its underlying molecular mechanism in
carbohydrate catabolism in vitro and in vivo. RESULTS: Isonitramine exerted
significant inhibitory effect on alpha-glucosidases but not alpha-amylase in
vitro. In zebrafish, isonitramine alleviated the streptozotocin (STZ)-induced
postprandial hyperglycemia and protected the pancreatic damages against alloxan
induced oxidative stress in vivo. Also, isonitramine induced insulin without any
toxicities and downregulated phosphoenolpyruvate carboxykinase (PEPCK), which
catalyzes the first committed step in gluconeogenesis. CONCLUSION: Taken
together, isonitramine inhibited alpha-glucosidase activity and PEPCK expression,
while increased insulin expression, resulting in attenuating the postprandial
hyperglycemia. Also, isonitramine protected the pancreas from ROS-mediated
toxicities. Therefore, isonitramine may be a new drug candidate for the treatment
of diabetes mellitus.
PMID- 28403935
TI - A prospective study of low fasting glucose with cardiovascular disease events and
all-cause mortality: The Women's Health Initiative.
AB - BACKGROUND: While there is increasing recognition of the risks associated with
hypoglycemia in patients with diabetes, few studies have investigated incident
cause-specific cardiovascular outcomes with regard to low fasting glucose in the
general population. OBJECTIVE: We hypothesized that low fasting glucose would be
associated with cardiovascular disease risk and all-cause mortality in
postmenopausal women. METHODS: To test our hypothesis, we used both continuous
incidence rates and Cox proportional hazards models in 17,287 participants from
the Women's Health Initiative with fasting glucose measured at baseline.
Participants were separated into groups based on fasting glucose level: low
(<80mg/dL), normal/reference (80-99mg/dL), impaired (100-125mg/dL), and diabetic
(>=126mg/dL). RESULTS: Participants were free of cardiovascular disease at
enrollment, had mean age of 62years, and were 52% Caucasian, 24% African
American, 8% Asian, and 12% Hispanic. Median follow-up was 15years. Graphs of
continuous incidence rates compared to fasting glucose distribution exhibited
evidence of a weak J-shaped association with heart failure and mortality that was
predominantly due to participants with treated diabetes. Impaired and diabetic
fasting glucose were positively associated with all outcomes. Associations for
low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98))
significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular
disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or
inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and
not significant. CONCLUSIONS: Fasting glucose at the upper range, but not the
lower range, was significantly associated with incident cardiovascular disease
and all-cause mortality.
PMID- 28403937
TI - Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo.
AB - INTRODUCTION: Brown adipose tissue (BAT) is a thermogenic organ with substantial
metabolic capacity and has important roles in the maintenance of body weight and
metabolism. Regulation of BAT is primarily mediated through the beta-adrenoceptor
(beta-AR) pathway. The in vivo endocrine regulation of this pathway in humans is
unknown. The objective of our study was to assess the in vivo BAT temperature
responses to acute glucocorticoid administration. METHODS: We studied 8 healthy
male volunteers, not pre-selected for BAT presence or activity and without prior
BAT cold-activation, on two occasions, following an infusion with hydrocortisone
(0.2mg.kg-1.min-1 for 14h) and saline, respectively. Infusions were given in a
randomized double-blind order. They underwent assessment of supraclavicular BAT
temperature using infrared thermography following a mixed meal, and during beta
AR stimulation with isoprenaline (25ng.kg fat-free mass-1.min-1 for 60min) in the
fasting state. RESULTS: During hydrocortisone infusion, BAT temperature increased
both under fasting basal conditions and during beta-AR stimulation. We observed a
BAT temperature threshold, which was not exceeded despite maximal beta-AR
activation. We conclude that BAT thermogenesis is present in humans under near
normal conditions. Glucocorticoids modulate BAT function, representing important
physiological endocrine regulation of body temperature at times of acute stress.
PMID- 28403938
TI - MondoA/ChREBP: The usual suspects of transcriptional glucose sensing; Implication
in pathophysiology.
AB - Identification of the Mondo glucose-responsive transcription factors family,
including the MondoA and MondoB/ChREBP paralogs, has shed light on the mechanism
whereby glucose affects gene transcription. They have clearly emerged, in recent
years, as key mediators of glucose sensing by multiple cell types. MondoA and
ChREBP have overlapping yet distinct expression profiles, which underlie their
downstream targets and separate roles in regulating genes involved in glucose
metabolism. MondoA can restrict glucose uptake and influences energy utilization
in skeletal muscle, while ChREBP signals energy storage through de novo
lipogenesis in liver and white adipose tissue. Because Mondo proteins mediate
metabolic adaptations to changing glucose levels, a better understanding of
cellular glucose sensing through Mondo proteins will likely uncover new
therapeutic opportunities in the context of the imbalanced glucose homeostasis
that accompanies metabolic diseases such as type 2 diabetes and cancer. Here, we
provide an overview of structural homologies, transcriptional partners as well as
the nutrient and hormonal mechanisms underlying Mondo proteins regulation. We
next summarize their relative contribution to energy metabolism changes in
physiological states and the evolutionary conservation of these pathways.
Finally, we discuss their possible targeting in human pathologies.
PMID- 28403936
TI - The short-term and long-term effects of bariatric/metabolic surgery on
subcutaneous adipose tissue inflammation in humans.
AB - CONTEXT: The mechanisms mediating the short- and long-term improvements in
glucose homeostasis following bariatric/metabolic surgery remain incompletely
understood. OBJECTIVE: To investigate whether a reduction in adipose tissue
inflammation plays a role in the metabolic improvements seen after
bariatric/metabolic surgery, both in the short-term and longer-term. DESIGN:
Fasting blood and subcutaneous abdominal adipose tissue were obtained before
(n=14), at one month (n=9), and 6-12months (n=14) after bariatric/metabolic
surgery from individuals with obesity who were not on insulin or anti-diabetes
medication. Adipose tissue inflammation was assessed by a combination of whole
tissue gene expression and flow cytometry-based quantification of tissue
leukocytes. RESULTS: One month after surgery, body weight was reduced by 13.5+/
4.4kg (p<0.001), with improvements in glucose tolerance reflected by a decrease
in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105+/
98mmol/L * min; p=0.009) and enhanced pancreatic beta-cell function
(insulinogenic index: +0.8+/-0.9pmol/mmol; p=0.032), but no change in estimated
insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p=0.720).
Furthermore, although biomarkers of systemic inflammation and pro-inflammatory
gene expression in adipose tissue remained unchanged, the number of neutrophils
increased in adipose tissue 15-20 fold (p<0.001), with less substantial increases
in other leukocyte populations. By the 6-12month follow-up visit, body weight was
reduced by 34.8+/-10.8kg (p<0.001) relative to baseline, and glucose tolerance
was further improved (AUC glucose -276+/-229; p<0.001) along with estimated
insulin sensitivity (Matsuda ISI: +4.6+/-3.2; p<0.001). In addition, improvements
in systemic inflammation were reflected by reductions in circulating C-reactive
protein (CRP; -2.0+/-5.3mg/dL; p=0.002), and increased serum adiponectin (+1358+/
1406pg/mL; p=0.003). However, leukocyte infiltration of adipose tissue remained
elevated relative to baseline, with pro-inflammatory cytokine mRNA expression
unchanged, while adiponectin mRNA expression trended downward (p=0.069).
CONCLUSION: Both the short- and longer-term metabolic improvements following
bariatric/metabolic surgery occur without significant reductions in measures of
adipose tissue inflammation, as assessed by measuring the expression of genes
encoding key mediators of inflammation and by flow cytometric immunophenotyping
and quantification of adipose tissue leukocytes.
PMID- 28403939
TI - Melanocortin 4 receptor is not required for estrogenic regulations on energy
homeostasis and reproduction.
AB - BACKGROUND: Brain estrogen receptor-alpha (ERalpha) is essential for estrogenic
regulation of energy homeostasis and reproduction. We previously showed that
ERalpha expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's
effects on food intake, body weight, negative regulation of hypothalamic
pituitary-gonadal axis (HPG axis) and fertility. RESULTS AND CONCLUSIONS: We
report here that global deletion of a key downstream receptor for POMC peptide,
the melanocortin 4 receptor (MC4R), did not affect normal negative feedback
regulation of estrogen on the HPG axis, estrous cyclicity and female fertility.
Furthermore, loss of the MC4R did not influence estrogenic regulation on food
intake and body weight. These results indicate that the MC4R is not required for
estrogen's effects on metabolic and reproductive functions.
PMID- 28403941
TI - Obesity is positively associated with arachidonic acid-derived 5- and 11
hydroxyeicosatetraenoic acid (HETE).
AB - BACKGROUND: Oxylipids are oxygenated polyunsaturated fatty acid (PUFA)
metabolites that are responsible for the onset and resolution of the inflammatory
response. Enzymatic oxygenation through the lipoxygenase (LOX) or cytochrome P450
(CYP) pathways can form oxylipids that have either proinflammatory or
proresolving functions depending on the type of PUFA substrate and degree of
metabolism. The objective of this study was to determine how PUFA substrates and
their corresponding oxylipids are associated with obesity. METHODS: Plasma non
esterified FA and oxylipids were isolated from 123 Caucasian males using solid
phase extraction and quantified using high performance liquid chromatography
tandem mass spectrometry. Statistical analyses included linear regressions and
polytomous logistic regressions, and the responses were body mass index (BMI) and
waist circumference (WC), and serum leptin, total adiponectin, interleukin-6 (IL
6), tumor necrosis factor-alpha (TNF-alpha), and C-peptide. Models were adjusted
for age and smoking, and p-values were corrected for false discovery per
Benjamini-Hochberg and Bonferroni. RESULTS: We report that BMI, WC, and several
serum cytokines were highly associated arachidonic acid (ARA)-derived
hydroxyeicosatetraenoic acids (HETEs), and vicinal diols (i.e., alcohols on
adjacent carbon atoms) derived from several PUFAs. There was a significant linear
relationship between BMI, WC, and serum leptin, and ARA-derived 5-, 11-, and 15
HETE. Specifically, BMI and WC were positively associated with proinflammatory 5-
and 11-hydroxyeicosatetraenoic acid (HETE), even after normalization to ARA
concentrations and false discovery p-value correction. Individuals with 5-HETE
concentrations >5.01nmol/L or 11-HETE concentrations and >0.89nmol/L were over 5
times more likely to be obese compared to those with <=1.86nmol/L and
<=0.39nmol/L, respectively. Vicinal diols from linoleic, eicosapentaenoic, and
docosahexaenoic acid were inversely associated with obesity. Across all
statistical tests, vicinal diols were inversely associated with obesity whether
normalized to parent PUFA concentrations or normalized to precursor epoxides.
Interestingly, the proinflammatory cytokines IL-6 and TNF-alpha were not
associated with any oxylipids. Since 5-HETE is a 5LOX product, 11-HETE is marker
of lipid peroxidation, and vicinal diols are formed through soluble epoxide
hydrolase (sEH) metabolism of CYP epoxygenated PUFAs, therefore, these results
indicate that obesity is likely associated with altered metabolism with distinct
oxygenating pathways. Taken together, our results indicate that obesity is
associated with specific oxylipids indicative of altered PUFA metabolism through
several pathways (i.e., LOX, reactive oxygen species, and sEH and CYP
epoxygenase), rather than attributed solely to altered dietary PUFA intake.
PMID- 28403940
TI - Vitamin D replacement in children, adolescents and pregnant women in the Middle
East and North Africa: A systematic review and meta-analysis of randomized
controlled trials.
AB - INTRODUCTION: Hypovitaminosis D affects one-third to two-thirds of children and
pregnant women from the Middle East and North Africa (MENA) region. OBJECTIVE: To
evaluate in infants, children, adolescents and pregnant women, from the MENA
region, the effect of supplementation with different vitamin D doses on the
change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non
skeletal outcomes. METHODS: This is a systematic review of randomized controlled
trials of vitamin D supplementation conducted in the MENA region. We conducted a
comprehensive literature search in 7 databases, without language or time
restriction, until November 2016. Two reviewers abstracted data from the included
studies, independently and in duplicate. We calculated the mean difference (MD)
and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each
comparison (low (<800IU), intermediate (800-2000IU) or high (>2000IU) daily dose
of vitamin D, or placebo). We pooled data using RevMan version 5.3. RESULTS: We
identified a total of 15 eligible trials: one in infants, 4 in children and
adolescents and 10 in pregnant women. In children and adolescents, an
intermediate vitamin D dose (1901IU/d), resulted in a mean difference in 25(OH)D
level of 13.5 (95% confidence interval (CI) 8.1-18.8) ng/ml, compared to placebo,
favoring the intermediate dose (p<0.001). The proportion of children and
adolescents reaching a 25(OH)D level>= 20ng/ml was 74% in the intermediate dose
group. In pregnant women, four trials started supplementation at 12-16weeks of
gestation and continued until delivery, and six trials started supplementation at
20-28weeks' gestation and stopped it at delivery. The MD in 25(OH)D level reached
was 8.6 (95% CI 5.3-11.9) ng/ml (p<0.001) comparing the high dose (3662IU/d) to
the intermediate dose (1836IU/d), and 12.3 (95% CI 6.4-18.2) ng/ml (p<0.001),
comparing the high dose (3399IU/d) to the low dose (375IU/d). Comparing the
intermediate (1832IU/d) to the low dose (301IU/d), the MD in 25(OH)D level
achieved was 7.8 (95% CI 4.5-10.8) ng/ml (p<0.001). The proportion of pregnant
women reaching a 25(OH)D level>=20ng/ml was 80%-90%, 73% and 27%-43% in the high,
intermediate, and low dose groups, respectively. The risk of bias in the included
studies, for children, adolescents and pregnant women, ranged from low to high
across all doamins. CONCLUSION: In children, adolescents and pregnant women from
the MENA, an intermediate vitamin D dose of 1000-2000IU daily may be necessary to
allow for the majority of the population to reach a desirable 25(OH)D level of
20ng/ml. Further high quality RCTs are required to confirm/refute the beneficial
impact of vitamin D supplementation on various clinically important outcomes.
PMID- 28403942
TI - MR signal-fat-fraction analysis and T2* weighted imaging measure BAT reliably on
humans without cold exposure.
AB - OBJECTIVE: Brown adipose tissue (BAT) is compositionally distinct from white
adipose tissue (WAT) in terms of triglyceride and water content. In adult humans,
the most significant BAT depot is localized in the supraclavicular area. Our aim
is to differentiate brown adipose tissue from white adipose tissue using fat T2*
relaxation time mapping and signal-fat-fraction (SFF) analysis based on a
commercially available modified 2-point-Dixon (mDixon) water-fat separation
method. We hypothesize that magnetic resonance (MR) imaging can reliably measure
BAT regardless of the cold-induced metabolic activation, with BAT having a
significantly higher water and iron content compared to WAT. MATERIAL AND
METHODS: The supraclavicular area of 13 volunteers was studied on 3T PET-MRI
scanner using T2* relaxation time and SFF mapping both during cold exposure and
at ambient temperature; and 18F-FDG PET during cold exposure. Volumes of interest
(VOIs) were defined semiautomatically in the supraclavicular fat depot,
subcutaneous WAT and muscle. RESULTS: The supraclavicular fat depot (assumed to
contain BAT) had a significantly lower SFF and fat T2* relaxation time compared
to subcutaneous WAT. Cold exposure did not significantly affect MR-based
measurements. SFF and T2* values measured during cold exposure and at ambient
temperature correlated inversely with the glucose uptake measured by 18F-FDG PET.
CONCLUSIONS: Human BAT can be reliably and safely assessed using MRI without cold
activation and PET-related radiation exposure.
PMID- 28403944
TI - Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the
EGIR-RISC cohort.
AB - OBJECTIVE: To study whether the shape of the oral glucose tolerance test (OGTT)
glucose curve is a stable trait over time; it is associated with differences in
insulin sensitivity, beta-cell function and risk of impaired fasting glucose
(IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity
and Cardiovascular Disease (RISC) cohort. METHODS: OGTT-glucose curve shape was
classified as monophasic, biphasic, triphasic and anomalous in 915 individuals.
Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI)
and beta-cell function were assessed at baseline and 3years apart. RESULTS: The
OGTT-glucose curve had the same baseline shape after 3years in 540 people (59%;
kappa=0.115; p<0.0001). Seventy percent of the participants presented with
monophasic OGTT-glucose curve shape at baseline and after 3years (percent
positive agreement 0.74). Baseline monophasic shape was associated with
significant increased risk of IFG (OR 1.514; 95% CI 1.084-2.116; p=0.015);
biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310-0.936) and
triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228-1.066; P=0.043)
after 3years. Increased risks of IFG (OR 1.509; 95% CI 1.008-2.260; p=0.05) and
IGT (OR 1.947; 95% CI 1.085-3.494; p=0.02) were found in people who kept stable
monophasic morphology over time and in switchers from biphasic to monophasic
shape (OR of IGT=3.085; 95% CI 1.377-6.912; p=0.001). CONCLUSION: After 3years
follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes
were associated with different OGIS and beta-cell function; persistence over time
of the monophasic shape and switch from biphasic to monophasic shape with
increased risk of impaired glucose metabolism.
PMID- 28403943
TI - Plasma metabolomics in adults with cystic fibrosis during a pulmonary
exacerbation: A pilot randomized study of high-dose vitamin D3 administration.
AB - BACKGROUND: Cystic fibrosis (CF) is a chronic catabolic disease often requiring
hospitalization for acute episodes of worsening pulmonary exacerbations. Limited
data suggest that vitamin D may have beneficial clinical effects, but the impact
of vitamin D on systemic metabolism in this setting is unknown. OBJECTIVE: We
used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin
D status and high-dose vitamin D3 administration on systemic metabolism in adults
with CF with an acute pulmonary exacerbation. DESIGN: Twenty-five hospitalized
adults with CF were enrolled in a randomized trial of high-dose vitamin D3
(250,000IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served
as a reference group for baseline comparisons. Plasma was analyzed with liquid
chromatography/ultra-high resolution mass spectrometry. Using recent HRM
bioinformatics and metabolic pathway enrichment methods, we examined associations
with baseline vitamin D status (sufficient vs. deficient per serum 25
hydroxyvitamin D concentrations) and the 7-day response to vitamin D3
supplementation. RESULTS: Several amino acids and lipid metabolites differed
between CF and healthy control subjects, indicative of an overall catabolic
state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D
status and were enriched within 7 metabolic pathways including fatty acid, amino
acid, and carbohydrate metabolism. A total of 316 metabolites, which showed
enrichment for 15 metabolic pathways-predominantly representing amino acid
pathways-differed between the vitamin D3- and placebo-treated CF subjects over
time (P<0.05). In the placebo group, several tricarboxylic acid cycle
intermediates increased while several amino acid-related metabolites decreased;
in contrast, little change in these metabolites occurred with vitamin D3
treatment. CONCLUSIONS: Numerous metabolic pathways detected by HRM varied in
association with vitamin D status and high-dose vitamin D3 supplementation in
adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data
suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical
setting.
PMID- 28403945
TI - Xanthine oxidoreductase activity is correlated with insulin resistance and
subclinical inflammation in young humans.
AB - BACKGROUND AND AIMS: The enzyme xanthine oxidoreductase (XOR) catalyzes the
formation of uric acid (UA) from hypoxanthine and xanthine, which in turn are
products of purine metabolism starting from ribose-5-phosphate. Besides the
synthesis of UA, basic research has suggested that XOR is involved in the
regulation of reactive oxygen species, adipogenesis, and peroxisome proliferator
activated receptor-gamma (PPAR-gamma). XOR activity has shown to be much lower in
humans than in rodents, which makes its accurate measurement difficult. Recently,
a novel human plasma XOR activity assay has been established using a combination
of liquid chromatography (LC) and triple quadrupole mass spectrometry (TQMS) to
detect [13C2,15N2]UA using [13C2,15N2]xanthine as a substrate. Using this novel
assay, we for the first time determine plasma XOR activity in humans, and
evaluate its association with insulin resistance, high-sensitivity C-reactive
protein (hsCRP) levels, and other parameters. METHODS: Of the 29 volunteers who
wished to participate in the study, 3 were excluded; of the remaining, 11 were
female and 15 were male with a mean age of 25.9+/-3.3years. Blood samples were
collected under fasting conditions in the early morning to measure XOR activity
and other parameters. RESULTS: The natural logarithmic value of XOR activity (ln
XOR) in plasma was 3.4+/-0.8pmol/h/mL. Ln-XOR had a positive correlation with UA
and body mass index (BMI) and a negative correlation with quantitative insulin
sensitivity check index (QUICKI) and adiponectin. In addition, ln-XOR had a
positive correlation with hsCRP levels, which serves as a marker of chronic
inflammation. CONCLUSIONS: The present study has shown that XOR activity is
correlated with serum UA levels in humans. Furthermore, even in young subjects,
XOR activity is correlated with insulin resistance, BMI, and subclinical
inflammation. Thus, XOR activity may be potentially involved in adiposity and
subclinical inflammation in humans.
PMID- 28403946
TI - Vitamin K and osteoporosis: Myth or reality?
AB - Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone
or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or
vitamin K2, is endogenously synthesized by intestinal bacteria and includes
several subtypes that differ in side chain length. Aside from its established
role in blood clotting, several studies now support a critical function of
vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin
carboxylation that in turn regulates bone mineral accretion; it seems to promote
the transition of osteoblasts to osteocytes and also limits the process of
osteoclastogenesis. Several observational and interventional studies have
examined the relationship between vitamin K and bone metabolism, but findings are
conflicting and unclear. This systematic review aims to investigate the impact of
vitamin K (plasma levels, dietary intake, and oral supplementation) on bone
health with a particular interest in bone remodeling, mineral density and
fragility fractures.
PMID- 28403947
TI - Berberine-induced bioactive metabolites of the gut microbiota improve energy
metabolism.
AB - OBJECTIVE: Berberine (BBR) clinically lowers blood lipid and glucose levels via
multi-target mechanisms. One of the possible mechanisms is related to its effect
on the short chain fatty acids (SCFAs) of the gut microbiota. The goal of this
study is to investigate the therapeutic effect and mode of action of BBR working
through SCFAs of the gut microbiota (especially, butyrate). METHODS: Gas
chromatography (GC) was used to detect butyrate and other SCFAs chemically. The
effect of BBR on butyrate production was investigated in vitro as well as in
several animal systems. Microarrays were used to analyze the composition change
in the intestinal bacteria community after treatment with BBR. BBR-induced change
in the energy production and gene regulation of intestinal bacteria was examined
in order to elucidate the underlying molecular mechanisms. RESULTS: We show that
oral administration of BBR in animals promoted the gut microbiota to produce
butyrate, which then enters the blood and reduces blood lipid and glucose levels.
Incubating gut bacterial strains in vitro with BBR increased butyrate production.
Orally treating animals directly with butyrate reduced blood lipid and glucose
levels through a mechanism different from that of BBR. Intraperitoneal BBR
administration did not increase butyrate but reduced blood lipid and glucose
levels, suggesting that BBR has two modes of action: the direct effect of the
circulated BBR and the indirect effect working through butyrate of the gut
microbiota. Pre-treating animals orally with antibiotics abolished the effect of
BBR on butyrate. A mechanism study showed that BBR (given orally) modified mice
intestinal bacterial composition by increasing the abundance of butyrate
producing bacteria. Furthermore, BBR suppressed bacterial ATP production and NADH
levels, resulting in increased butyryl-CoA and, eventually, butyrate production
via upregulating phosphotransbutyrylase/butyrate kinase and butyryl-CoA:acetate
CoA transferase in bacteria. CONCLUSION: Promotion of butyrate (etc) production
in gut microbiota might be one of the important mechanisms of BBR in regulating
energy metabolism.
PMID- 28403948
TI - Association between early pregnancy vitamin D status and changes in serum lipid
profiles throughout pregnancy.
AB - OBJECTIVE: To evaluate the associations between first trimester 25-hydroxyvitamin
D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c),
low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride
(TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We
hypothesized that first trimester 25(OH)D inadequacy is associated with lower
concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios
throughout pregnancy. METHODS: A prospective cohort study with 3 visits at 5-13
(baseline), 20-26, and 30-36 gestational weeks, recruited 194 pregnant women
attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D
concentrations were measured in the first trimester using liquid chromatography
tandem mass spectrometry. 25(OH)D concentrations were classified as adequate
(>=75nmol/L) or inadequate (<75nmol/L). Serum TC, HDL-c, and TG concentrations
were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects
models were employed to evaluate the association between the first trimester
25(OH)D status and changes in serum lipid concentrations throughout pregnancy.
Confounders adjusted for in the multiple analysis were age, homeostatic model
assessment (HOMA), early pregnancy BMI, leisure time physical activity before
pregnancy, energy intake, and gestational age. RESULTS: At baseline, 69% of the
women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had
higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5mg/dL;
P=0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios,
increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for
repeated measures P<0.001). The adjusted models showed direct associations
between the first trimester 25(OH)D status and changes in TC (beta=9.53;
95%CI=1.12-17.94), LDL-c (beta=9.99; 95% CI=3.62-16.36) concentrations, and
TC/HDL-c ratios (beta=0.16; 95% CI=0.01-0.31) throughout pregnancy. CONCLUSIONS:
Inadequate plasma 25(OH)D concentrations during early pregnancy were associated
with more pronounced changes of TC, LDL-c concentrations, and TC/HDL-c ratios
throughout pregnancy. Changes in these cardiovascular markers suggest the
importance of ensuring adequate vitamin D status at the beginning of pregnancy.
PMID- 28403950
TI - The effect of dehydroepiandrosterone (DHEA) supplementation on women with
diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis.
AB - To evaluate the effect of dehydroepiandrosterone (DHEA) therapy on the ovarian
response and pregnancy outcome in patients with diminished ovarian reserve (DOR).
Eligible studies, published before August 31, 2015, were identified from PubMed,
EMBASE, the Cochrane library. Outcome measures were the number of retrieved
oocytes, cancellation rate of IVF cycles, clinical pregnancy rate and miscarriage
rate. We adopted Revman 5.0 software to pool the data from the eligible studies.
A total of 9 studies, four were RCTs, four retrospective studies, one prospective
studies, including 540 cases and 668 controls, were available for analysis. The
pooled analysis showed that the clinical pregnancy rates were increased
significantly in DOR patients who were pre-treated with DHEA (OR=1.47, 95% CI:
1.09-1.99), whereas no differences were found in the number of oocytes retrieved,
the cancellation rate of IVF cycles and the miscarriage rate between the cases
and controls (WMD= -0.69, 95% CI: -2.18-0.81; OR=0.74, 95% CI: 0.51-1.08;
OR=0.34, 95% CI: 0.10-1.24). However, it is worth noting that when data were
restricted to RCTs, there was a non-significant difference in the clinical
pregnancy rate (OR=1.08, 95% CI: 0.67-1.73). We concluded that DHEA
supplementation in DOR patients might improve the pregnancy outcomes. To further
confirm this effect, more randomized controlled trials with large sample sizes
are needed.
PMID- 28403951
TI - Successful use of a Bakri Tamponade Balloon in the treatment of puerperal uterine
inversion during caesarean section.
AB - Acute puerperal inversion of the uterus is a rare life-threatening obstetric
emergency, especially during caesarean section. We present the case of a 30-year
old patient with acute puerperal inversion of the uterus that occurred during
placental removal. After a quick reversion of the uterus, an immediate postpartum
haemorrhage (PPH) due to massive uterine atony was observed. This atony impacted
the whole uterus, with a very thin uterine myometrium. The use of a Bakri
Tamponade Balloon use allowed treating extreme uterine atony, immediately stop
haemorrhage, and prevent a possible risk of immediate recurrence.
PMID- 28403949
TI - Racial differences in circulating levels of the soluble receptor for advanced
glycation endproducts in middle-aged and older adults.
AB - BACKGROUND: Low levels of the soluble receptor for advanced glycation endproducts
(sRAGE) have been implicated in a number of chronic diseases. Previous studies
indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However,
the reasons for these differences are unclear. PURPOSE: We aimed to identify
predictors of circulating sRAGE biomarkers among Black and White adults at high
cardiac risk. METHODS: Serum levels of total sRAGE, endogenous secretory RAGE
(esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were
measured in 99 Blacks and 454 Whites. RESULTS: Blacks had a more adverse
cardiovascular risk profile, as well as lower median levels of total sRAGE (972
vs. 1564pg/ml) and esRAGE (474 vs. 710pg/ml) compared to Whites (p<0.0001). In
addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as
were the CML/total sRAGE (0.89 vs. 0.56ng/pg) and CML/esRAGE (1.72 vs. 1.20ng/pg)
ratios (p<0.0001). Racial differences persisted after adjustment for key
covariates including age, gender, tobacco use, comorbidities, BMI, blood
pressure, glucose, insulin, triglycerides, C-reactive protein, and renal function
(p<0.05). Race alone accounted for nearly half of the variability in total sRAGE
levels (10.6%; model explained 23.9%). In stratified analyses, gender and heart
rate were independently associated with total sRAGE and esRAGE in Whites, while
CML and C-reactive protein were associated with total sRAGE in Blacks.
CONCLUSIONS: We identified several independent predictors of sRAGE biomarkers.
Notably, Black race was associated with an adverse AGE/RAGE profile, including
lower sRAGE and higher CML/sRAGE ratios.
PMID- 28403952
TI - Vaginocutaneous fistula and buttock abscess formation 7 years after polypropylene
transobturator tape insertion.
AB - Surgical treatment for stress urinary incontinence (SUI) using transobturator
tape insertion is widely accepted. However, several postoperative complications
were reported in the literature including infections, abscess and fistula
formation. Here, we report a case of 57-year-old female who presented with
abscess and left vaginocutaneous buttock fistula 7 years after transobturator
polypropylene tape insertion. Treatment included abscess drainage with dissection
of the fistulous tract and removal of the left arm of the transobturator tape
along with antibiotic coverage. Sinus drainage stopped after 3 days. Stress
urinary incontinence did not recur. Suspicion of fistula formation should rise in
patients presenting with bothersome vaginal or cutaneous discharge after
transobturator tape insertion. This case is particular since it describes a
fistula complication with polypropylene tape, which is unusual with this type of
tapes. Treatment of such complication should always consist of surgical removal
of the mesh to allow closure of the fistulous tract.
PMID- 28403953
TI - Risk factors of preterm birth in France in 2010 and changes since 1995: Results
from the French National Perinatal Surveys.
AB - OBJECTIVES: To investigate risk factors of total, spontaneous and induced preterm
birth in 2010 and differences between 1995 and 2010. MATERIAL AND METHODS: The
national perinatal surveys are based on a representative sample of births in
France. We selected live-born singletons (n=14,326 in 2010 and 12,885 in 1995)
and used multiple regression analyses to calculate adjusted odds ratios (aOR) for
maternal sociodemographic characteristics, obstetric history, prenatal care and
smoking. RESULTS: The main risk factors in 2010 were parity 1 compared to parity
2 (aOR=1.9 [95% CI 1.5-1.3]), previous preterm delivery (aOR=6.6 [5.0-8.7]), pre
pregnancy body mass index<18.5 compared to 18.5-24.9kg/m2 (aOR=1.7 [1.4-2.2]),
level of education completed: high school or less, inadequate prenatal care and
cannabis use. Most risk factors of spontaneous and induced preterm births were
similar. Compared to 1995, maternal age>=35 years and previous induced abortion
were no longer associated with preterm birth in 2010. CONCLUSION: Identified risk
factors for preterm birth in France in 2010 agree with the literature. Increases
in baseline rates for maternal age and medically induced abortions may explain
changes in certain preterm birth risk factors.
PMID- 28403954
TI - Effectiveness and safety of induction of labor for term breech presentations.
AB - : In term breech deliveries, vaginal delivery can be safely envisioned in some
conditions (related to patient selection and obstetrician experience). Very few
data are currently available, however, about the possibility of inducing labor in
these situations. OBJECTIVE: To assess the effectiveness and safety of induction
of labor for breech presentations. STUDY DESIGN: Retrospective comparative
hospital-based study of a continuous series of term breech deliveries from 2000
to 2010. The condition of term breech newborns delivered vaginally after
induction of labor was compared to that of their counterparts delivered vaginally
after spontaneous labor. RESULTS: During the study period, 96 women with term
fetuses in breech presentations had labor induced and 501 in spontaneous labor
had attempted vaginal deliveries. Compared with spontaneous labor, induction was
not associated with a significantly higher rate of cesarean delivery during labor
(20.8 vs 14.8%, P=0.14), nor with poorer neonatal condition, defined either as
moderate acidosis (pH<7.15; 21.6 vs 19.8%, P=0.71) or composite neonatal
morbidity (2.1 vs 0.6%, P=0.16). CONCLUSION: Our data indicate that, compared
with spontaneous labor, neither cervical ripening nor oxytocin induction of labor
is associated with either a poorer neonatal prognosis or an excess rate of
obstetric complications in term breech births, and that the success rate of
induction is satisfactory.
PMID- 28403955
TI - French prenatal Vitamin D recommended supplementation: Enough or not?
AB - OBJECTIVE: To determine the impact of current recommended vitamin D prenatal
supplementation on blood cord 25(OH)D level in a French cohort and to determine
population at risk of higher needs. DESIGN AND SETTING: An observational
prospective study was conducted in teaching hospital including two large groups
of newborns, one born after summer and another after winter period. PATIENTS AND
METHODS: Three hundred and ninety-nine mother/newborns pairs were enrolled and
blood cord results were available for 225 newborns in the post-summer group and
174 newborns in the post-winter group. Maternal supplementation during pregnancy
was recorded from medical notes and questionnaires. RESULTS: 25(OH)D level were
generally low with mean at 50.9+/-24.7nM. Vitamin D supplementation was
prescribed in only 37.6% over all the study period. Studying general population,
25(OH)D was significantly higher in the supplemented group, but current
recommended supplementation failed to cover the needs for most subgroups of
newborns. After winter, 25(OH)D cord blood level was in deficiency range for
40.7% of the general population and in the pigmented mothers group the deficiency
rates even rose up to 61.9%. DISCUSSION AND CONCLUSION: Vitamin D cord level is
low in north of France as in other industrial countries. Despite national
guidelines on vitamin D supplementation, the rates are currently insufficient.
Beside, although the recommended 100,000IU single dose helps to limit deficiency
in newborns, it fails to cover infant's needs for optimal status. Actually,
benefit of this substitution is for children below the 10th percentile weight. A
new recommendation with higher rate of vitamin D for all pregnant women after
specific studies seems to be indicated.
PMID- 28403956
TI - Severe perineal morbidity of instrumental deliveries using Thierry's spatulas and
vacuum extraction: A prospective observational cohort study.
AB - OBJECTIVES: To evaluate the risk of severe perineal tear following instrumental
vaginal delivery (IVD) performed with spatulas and vacuum extraction. Secondary
objectives were to estimate the impact of episiotomy on this risk. METHODS: From
December 2008 to October 2012, women who underwent spatulas or vacuum were
prospectively included. Each spontaneous vaginal delivery (SVD) following each
included IVD were included as control cases (1-1 ratio). Careful perineal
examination was systematically performed. Severe perineal tear was defined by the
occurrence of anal sphincter rupture with or without anal mucosa tear. RESULTS: A
total of 761 patients were included in the current study: 248 (64%) spatulas, 137
(36%) vacuums and 381 (49%) SVDs. Severe perineal tear was diagnosed in 19 (2.5%)
cases. Episiotomy had been performed in 276 (36.9%) patients. Only spatulas
extraction was found to significantly increase the risk of severe perineal tear
(AOR=7.66; 95% CI: 2.06-28; P=0.02). Although vacuum extraction seemed to
increase this risk, it was not found to be significant (AOR=3.25; 95% CI: 0.65
16.24; P=0.15). No significant difference was observed between the risk of severe
perineal tear following spatulas and vacuum (AOR=2.36; 95% CI: 0.63-8.82;
P=0.202). Finally, neither foetal macrosomia, nor episiotomy, nor foetal
extraction with the head in the deep pelvis, nor delivery at night had a
significant impact on the probability of severe perineal tear. CONCLUSIONS:
Spatulas extraction is an independent risk factor for severe perineal tear. The
practice of episiotomy was not shown to have any significant impact on this risk.
PMID- 28403957
TI - Effectiveness of elective cervical cerclage according to obstetric history.
AB - OBJECTIVE: To assess the effectiveness of elective history-indicated cervical
cerclage according to obstetrical history. STUDY DESIGN: We analyzed pregnancy
outcome of a retrospective cohort of women who have had history-indicated
McDonald's cerclage. Principal outcome was gestational age (GA) at delivery.
RESULT: Between January 2003 and December 2013, 205 women were included. We
analyzed population in two risk groups: 1- Low-risk (<=2 prior preterm birth
(PTB)/second trimester loss (STL), or prior success of cerclage), 2- High risk
(>=3 prior PTB/STL, or prior failure of cerclage). In the high-risk group, there
was a higher frequency of deliveries before 37 weeks (47.5% vs. 24.5%, P=0.001,
OR=2.79, 95% CI [1.49-5.23]). Fifty percent of women (n=6/12) delivered before 37
weeks in case of three or more prior PTB/STL, and 51% (n=24/47) in case of prior
failure of cervical cerclage. CONCLUSION: Elective cervical cerclage may be
indicated for women with<=2 prior PTB/STL, or prior successful cerclage. For
women with>=3 prior PTB/STL, trachelorraphy or cervico-isthmic cerclage could be
possible alternatives to cervical cerclage.
PMID- 28403958
TI - Practice of pathological examinations in stillbirths: A 10-year retrospective
study.
AB - OBJECTIVES: To describe the practice of fetal and placental pathological
examinations in a large series of spontaneous stillbirths over 10 years.
MATERIALS AND METHODS: Inclusion of cases recorded by the Lower Normandy Regional
Fetal-Infant Mortality Observatory (observatoire regional de mortalite foeto
infantile) from January 1, 2005 to December 31, 2014. The possible cause of death
was coded in accordance with the ReCoDe classification system. RESULTS: Seven
hundred and forty-four cases were recorded. The placental examinations were
conducted in 93.7% of cases (CI95%[91.7-95.3]), increasing over the study period,
and an autopsy was proposed in 87.2% of cases (CI95%[84.8-89.6]). Autopsy was
conducted less frequently during the most recent period, with parental refusal
increasing over time. In multivariate analysis, no factor was associated with a
higher frequency of placental examinations, while autopsy was proposed more often
under certain circumstances: less than 4 pregnancies (P<10-2), birth weight from
1000 to 1500 grams (P=0.05), singleton (P<10-2), clinical context not suggesting
a cause (P<10-3), type 1 or 2 maternity ward (P<10-2), antepartum death (P<10-3).
CONCLUSION: Placental analysis was almost systematically realized, as suggested
by international guidelines. Fetal autopsy was often performed, however only in
some specific circumstances. New practice guidance to realize customized fetal
autopsies appear to be necessary.
PMID- 28403959
TI - Impact of the French 3rd and 4th generation pill scare in women seeking
termination of pregnancy.
AB - INTRODUCTION: The aim of this study was to evaluate changes in the contraceptive
profile of women seeking termination of pregnancy following the debate on 3rd and
4th generation pills in France in 2012. MATERIALS AND METHODS: Single-center case
control study comparing the attitude to contraception before (between 02/15/2012
and 07/16/2012) and after the debate (between 02/25/2013 and 06/24/2013).
RESULTS: A total of 291 patients consulted before and 601 after the debate. We
showed that there were more students (+9.5%), more single women (+8.3%) and fewer
working women (-7.7%) in the cohort after the debate. After the termination
procedure, prescriptions for long-acting reversible contraceptive (LARC) methods
increased (+7.8%, P=0.03), in particular in patients aged 25 or younger,
including nulliparous (+12.6%, P=0.02). CONCLUSION: The media alert about the
pill led to a change in the contraceptive standard in the post-abortion period
and altered patient profiles. An increase was notably observed in certain
vulnerable populations (high school students, unemployed and single women). It
remains to be seen whether these changes are transient or permanent.
PMID- 28403960
TI - Anatomical causes of difficult embryo transfer during in vitro fertilization.
AB - OBJECTIVES: Identify, define and validate through statistical analysis the
anatomical causes of difficult embryo transfers (ET). MATERIALS AND METHODS: This
observational study, carried out in 306 IVF candidates, compared the frequency of
anatomical anomalies of the uterus and cervix in women who underwent an easy ET
with that in women who underwent a difficult ET. Anatomical anomalies were
detected during an assessment of the cervix and uterus including transvaginal
ultrasound, hysteroscopy and a mock transfer. Ease of ET was determined during
the actual transfer procedure. RESULTS: An easy ET was achieved in 151 patients,
whereas difficulties occurred in 155 patients, among whom 55 patients underwent a
"very difficult" ET. The most common anatomical characteristics associated with
difficult ET were abnormal crypts in the cervical canal (86%) and tortuosity of
the cervical canal (68%). Less frequent causes included: internal os contractions
(28%) and pronounced anteversion of the uterus (26%). Very difficult ETs were
associated with the presence of several causes. CONCLUSIONS: ET is the clinical
step that has the most effect on IVF outcome. Difficult transfers are associated
with a fall in pregnancy rates. The anatomical causes of difficult transfer
identified in this study led to major changes in transfer procedure in our
department and to the development of more adapted catheters.
PMID- 28403961
TI - Vascular endothelial growth factor antagonist reduces the early onset and the
severity of ovarian hyperstimulation syndrome.
AB - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is the most serious
complication of controlled ovarian stimulation (COH) during assisted reproductive
technology (ART) protocols. This syndrome is a result of ovarian expression of
vascular endothelial growth factor (VEGF), which increases vascular permeability.
OBJECTIVES: To evaluate the efficiency of prophylactic and therapeutic use of
cabergoline in women with higher risk of developing OHSS. MATERIALS AND METHODS:
In this prospective randomized study, 146 women undergoing in vitro fertilization
(IVF) cycles with GnRH agonist protocols with a higher risk of OHSS diagnosed
during the HCG day administration (more than 18 follicles observed larger than
12mm in diameter during COH and/or estradiol levels of 3000-3500pg/ml, previous
episodes of OHSS). Women were randomly divided in two groups. The first group
included 78 women who received 0.5mg per day of cabergoline (Dostinex(r)) orally
for 7 days starting from hCG administration day. The second group included 68
women who received no medication treatment. Overall, in each group 25 patients
have developed OHSS. This defines subgroup 1 that includes 25 cases of OHSS
obtained in group 1 and subgroup 2 where 25 cases of OHSS obtained in group 2.
Early OHSS was defined as being when the onset of the syndrome was initiated
during the first 9 days after hCG administration and late OHSS was defined as
being when the onset of the syndrome was initiated from 10 days after hCG
administration. Outcome measures of this study were the incidence of moderate and
severe OHSS, early or late OHSS and pregnancy rates. RESULTS: There was no
evidence of a statistically significant reduction in the incidence of OHSS in
cabergoline group (32.05% vs. 36.76%; P>0.05). Late OHSS was observed in 60.6% of
cases in cabergoline group while 39.4% of cases in the other group (P=0.036).
Early OHSS decreased significantly (P<0.05) in the cabergoline group. Severe OHSS
cases were more common within subgroup 2 than subgroup 1 (32% vs. 8%, P=0.000).
There was no difference in clinical pregnancy rates (PR) and miscarriages rates
between the two subgroups. CONCLUSIONS: The cabergoline administration
(Dostinex(r)) for patients with high-risk of OHSS can reduce the rate of early
OHSS and its severity in GnRH agonist IVF cycles, but cannot prevent the
incidence of OHSS.
PMID- 28403962
TI - Management of deep infiltrating endometriosis by laparoscopic route with robotic
assistance: 3-year experience.
AB - OBJECTIVE: To assess the feasibility of deep endometriosis surgery using robotic
assistance, benefits and limits of this approach. METHOD: Case-series study
enrolling patients managed for deep infiltrating endometriosis (DIE) using
robotic assistance in our department between September 2011 and March 2014
(NCT02294825). Self-questionnaires including pain and digestive symptoms were
filled in preoperatively and 1 year after surgery. RESULTS: Thirty-five patients
were enrolled in the series. They represented 54% of patients managed for
gynecological disease by laparoscopic route with robotic assistance during the
study period, and 14% of patients managed for deep endometriosis in our
department. Follow-up averaged 24+/-8 months, and no patient was lost to follow
up. Thirty-two patients had rectal involvement: rectal shaving was performed in
25 patients, disc excision in 3 and colorectal resection in 4. Three patients had
bladder resection. Thirteen patients presented with deep endometriosis of the
ureters: ureterolysis was performed in 11 of them, and resection of the ureter
followed by reimplantation into the bladder in 2 patients. One major complication
(Clavien IIIb) was recorded in a patient presenting with necrosis of the right
ureter on postoperative day 5. Nine patients tried to conceive after surgery and
8 have already become pregnant (88.9%). One year after surgery, self
questionnaires revealed a significant decrease in pain symptoms and significant
improvement in several item values of gastrointestinal standardized
questionnaires. CONCLUSIONS: Surgical management of DIE is feasible using robotic
assistance. However, data available in the literature and our own experience do
not definitively support the hypothesis of the superiority of robotic assistance
in the management of DIE.
PMID- 28403963
TI - The WNT/beta-catenin signaling pathway may be involved in granulosa cell
apoptosis from patients with PCOS in North China.
AB - INTRODUCTION: Investigate the expressions of WNTs in granulosa cells of PCOS in
North China, and explore the possible mechanism. MATERIAL AND METHODS: Patients
with PCOS (n=40) and controls without PCOS (n=20) were enrolled into the study.
The levels of serum sex hormone were detected by chemiluminescent enzyme
immunoassay. RT-qPCR was used to measure mRNA levels of WNT family members (WNT1,
WNT3, WNT4, WNT5, sFRP4 and sFRP5). The levels of Bax and Bcl-2 were measured by
enzyme-linked immunosorbent assay. RESULTS: The levels of PROG, TES and LH/FSH
had difference (p<0.05) on third day of menstrual cycle between PCOS and control
groups. After injection of HCG, the levels of LH, E2 and PROG had significant
difference (p<0.05). The PCOS group had higher transcript levels of WNT1, WNT3
and WNT4 (p<0.05), compared to controls. The level of secreted frizzled-related
protein (sFRP4) was lower level in PCOS patients (p<0.05). In addition, we found
a significant reduction of the beta-catenin as well as the downstream targets
(survivin and BMP4) (p<0.05). The level of Bax was significantly higher in PCOS
group than in the control group (p<0.05). Above all, the WNT/beta-catenin
signaling pathway might be involved into granulosa cell apoptosis, which may
provide a strategy for clinical treatment.
PMID- 28403964
TI - [Can new molecular profiles in epithelial ovarian cancer modify therapeutics?]
AB - Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a
survival of 30% at 5 years. Treatment is based on extensive surgery and
chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition
essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are
described (serous, endometrioid, and mucinous cells to clear), corresponding to
different carcinogenesis and distinct molecular mutations. High-grade serous EOCs
have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a
deficit of repair by homologous recombination of DNA in case of double strand
break, allowing greater sensitivity to platinum salts and the use of PARP
inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP
inhibitors have shown efficacy in patients mutated BRCA but this effectiveness
remains to be demonstrated in patients without congenital mutation, but with
acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having
a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular
definition of BRCAness is still not consensual but is necessary for the use of
PARP inhibitors. Gene expression analyses have identified four subgroups of high
grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive.
These four subtypes, not mutually exclusive, although correlated with prognosis,
are not yet used in clinical routine.
PMID- 28403965
TI - Understanding fetal physiology and second line monitoring during labor.
AB - Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition
and is one of the most common obstetric procedures. Second line methods of fetal
monitoring have been developed in an attempt to reduce unnecessary interventions
due to continuous cardiotocography and to better identify fetuses at risk of
intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal
blood scalp samples, the modification of the myocardial oxygenation by the fetal
ECG ST-segment analysis (STAN) and the autonomic nervous system by the power
spectral analysis of the fetal heart variability. To correctly interpret the
features observed on CTG traces or second line methods, it seems important to
understand normal physiology during labor and the compensatory mechanisms of the
fetus in case of hypoxemia. Therefore, the aim of this review is first to
describe fetal physiology during labor and then to explain the modification of
the second line monitoring during labor.
PMID- 28403966
TI - [Intrauterine blood transfusion: Status report of 4years of practice in France
(2011-2014)].
AB - OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's
(IUT) performed in France, among the French prenatal diagnosis centers in order
to study the etiology of severe anemia requiring IUT. METHODS: We conducted a
national retrospective descriptive study between 2011 and 2014. The data were
collected using a survey sent by email to all French prenatal diagnosis centers.
RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during
the study period. The geographical repartition of these centers was appropriate
for the "Aquitaine Pyrenees" region. Five centers performed 68 % of the national
activity and one center performed 40 % the national activity. Each year, a mean
of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe
fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the
etiologies) with anti-RhD being the most prevalent antibody. The second etiology
was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The
French IUT activity was stable in numbers and indications during the study
period. A national register could be set up in order to better evaluate
prospectively the number of pregnancies concerned by IUT and to study the
prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.
PMID- 28403967
TI - Organization and first results of cervical cancer screening program in Mayotte,
from 2010 to 2014.
AB - OBJECTIVES: Our main goal was to report the organization of individual screening
for uterus cancer in Mayotte, the last French department since 2011, and its
first results. MATERIAL AND METHODS: Epidemiological and observational study
describing the prior situation, the beginning of the screening with pap smears in
2010, the colposcopy consultations and the treatment of the patients by the
Mayotte network for screening of cancers since 2010. RESULTS: The screening
allowed an improvement of the global cover rate from 5% to 24% in 5 years. The
best results concern the woman from 25 to 39 years old, with a rate that rose
from 14 to 46%. CONCLUSION: This study confirms the possibility and the
efficiency of a screening program on this island, which is French by law, by much
closer to developing countries on many other sides.
PMID- 28403968
TI - Inter-observer reliability of 4 fetal heart rate classifications.
AB - OBJECTIVE: Different classification of fetal heart rate (FHR) pattern have been
proposed: FHR classified as either "reassuring" or "non-reassuring", the National
Institute of Child Health and Human Development (NICHD) published in 2008 a 3
tier system, the French College of Gynecology and Obstetrics (CNGOF) recommended
in 2013 a 5-tier system and recently in 2015, the Federation International of
Gynecology and Obstetrics (FIGO) proposed a new classification based on a 3-tier
system. Our objective was to assess the inter-observer reliability of these 4
existing classifications. STUDY DESIGN: Four observers reviewed 100 FHR without
clinical information. FHR were obtained from term singleton pregnancies. Fetal
heart rate patterns were classified by one 2-tier ("reassuring vs. non
reassuring"), two 3-tier (NICHD 2008 and FIGO 2015), and one 5-tier (CNGOF 2013)
fetal heart classifications. RESULTS: The global agreement between observers was
moderate for each classification: 0.58 (0.40-0.74) for the 2-tier, 0.48 (0.37
0.58) for the NICHD 2008, 0.58 (0.53-0.63) for the CNGOF 2013 and 0.59 (0.49
0.67) for the FIGO 2015 classification. When FHR was classified as reassuring, it
was classified as normal in 85.5% for the NICHD 2008 and in 94.5% for the FIGO
2015. For the CNGOF 2013, 65.0% were classified as normal and 32.5% as quasi
normal. There was strong concordance between FIGO category I and "reassuring" FHR
(kappa=0.95). CONCLUSION: Inter-observer agreement of FHR interpretation is
moderate whatever the classification used. To evaluate the superior interest of
one classification, it will be interesting to compare their impact on need of
second line techniques and on neonatal outcome.
PMID- 28403969
TI - SF-36 preoperative interest of predicting improvement of quality of life after
laparoscopic management of minimal endometriosis.
AB - THE PURPOSE OF THE STUDY: To study preoperative thresholds of the SF-36
components above which we can predict a high risk of failure in order to improve
the quality of life after surgery for patients with minimal endometriosis.
MATERIAL AND METHODS: Design: prospective and multicenter observational study
between February 2004 and 2011. PATIENTS: 167 patients with operated minimal
endometriosis. SETTING: for the Physical Component Summary (PCS) or the Mental
Component Summary (MCS) subscales of the SF-36 questionnaire, an improvement
defined by an increase of 5 points. INTERVENTION: evaluation by the SF-36
questionnaire the week before and one year after surgery. MEASUREMENT AND MAIN
RESULTS: Success of surgery measured by an improvement in both components. We
found significantly different initial variables between patients with improvement
and those without: initial MCS score (P=0.0003), initial PCS score (P<0.0001) and
dyspareunia (P=0.004). Multivariate analysis revealed only two significant
variables. Initial MCS higher than 40 (OR=4.6) and initial PCS higher than 50
(OR=10.6) are risk factors for failure of improvement after surgery. CONCLUSION:
Surgery is seldom a good treatment for improving QOL in minimal endometriosis. We
set two thresholds for SF-36, 50 for PCS and 40 for MCS: above there is a very
high risk of failure (86% of failure in our population). Under, the risk of
failure remains high (54.3%). CANADIAN TASK FORCE CLASSIFICATION OF STUDY DESIGN:
Evidence obtained from well-designed cohort or case-control studies, preferably
from more than one center or research group.
PMID- 28403970
TI - Fertility after surgery for deep infiltrating endometriosis.
AB - OBJECTIVES: The population of Reunion Island has a high prevalence of
endometriosis impacting fertility. The aim of this series is to assess the
fertility of women undergoing surgical approach of deep infiltrating
endometriosis and to study the characteristics of the pregnancy outcomes.
MATERIAL AND METHODS: This is a retrospective 2 centers study, including all
women wanting to be pregnant and operated for deep endometriosis in any of the 2
hospitals of the CHU of Reunion Island between January 2012 and May 2013.
RESULTS: Sixty-three women were included. Twenty-four (38%) had more than one
operation and 16 (25.4%) experienced one or more complications. Fifty-eight (92%)
had complete resection of the endometriosis. Twenty-seven (42.9%) women became
pregnant at least once, spontaneously in 44.4%. Average delay for first pregnancy
was 14.2 months. Twenty-two (34.9%) women became pregnant before 24 months. Among
the 34 pregnancies, 20 ended with a live newborn. Premature delivery rate was
35%, cesarean section rate 10% and average birth weight was at 45th percentile.
CONCLUSION: Fertility remains good after surgery for deep infiltrating
endometriosis but the delay between operation and pregnancy is increased when a
surgical complication occurs. Premature delivery rate is high. No pregnancy
occurred in case of incomplete resection or after age of 36.
PMID- 28403971
TI - [Performances of breast magnetic resonance imaging in the context of neoadjuvant
chemotherapy for breast cancer to predict pathological complete response].
AB - PURPOSE: The objective of this work was to estimate the reliability of MRI after
neoadjuvant chemotherapy (NAC) for breast cancer to detect a residual tumour by
comparing the tumoral size measured by MRI with the histological size. We also
estimated the concordance of diagnosis of complete pathological response between
histological examination and MRI. MATERIALS AND METHODS: We included all the
patients who received a neoadjuvant chemotherapy for breast cancer in the
university hospital of Tours from January, 2008 to December 31st, 2012 and in the
comprehensive cancer centre of Rennes from January, 2008 till May 31st 201. We
considered that the pathological response was complete (pCR) when there was no
residual invasive tumour in the mammary surgical specimen. RESULTS: Two hundred
and fifty-one women who received NAC for a non-metastatic breast cancer were
included in the study: 103 in Tours and 148 in Rennes. Two women (0.8%) refused
breast surgery whatever the type. One hundred and twenty-three (49%) women had a
breast conservative surgery. One hundred and fifteen (45.8%) had a mastectomy and
11 (4.4%) had breast conservative surgery followed by mastectomy for positive
margins. A complete pathological response was present in 54 cases (21.5%). We did
not found any significant difference between characteristics of patients with pCR
or not. CONCLUSION: Breast MRI remains the most performing examination to
evaluate the initial tumoral size and the residual tumour after NAC, but does not
add any value at mid or at the end of treatment for the patients to whom a
mastectomy is decided at presentation. The correlation between the breast MRI and
the histology size is not perfect, but at the moment, MRI stills of the most
performing examination to predict the pCR.
PMID- 28403972
TI - Low pressure gynecological laparoscopy (7mmHg) with AirSeal(r) System versus a
standard insufflation (15mmHg): A pilot study in 60 patients.
AB - OBJECTIVES: To evaluate feasibility of performing benign gynecologic pathology
low pressure (7mmHg) laparoscopy (LPL) with AirSeal(r) system and to study
benefits in terms of postoperative pain, when compared to a standard insufflation
group (15mmHg). MATERIALS AND METHODS: In this prospective randomized pilot
study, 60 patients had laparoscopy for gynecologic benign pathology: 30 with
7mmHg and AirSeal system, and 30 with 15mmHg standard insufflator. The primary
endpoint was incidence of shoulder pain. A postoperative questionnaire was
completed by each patient to assess shoulder pain (Numeric Rating Scale [NRS],
from 0 to 10) at H4, H8, H24, and consumption of morphinics was notified. During
each procedure, anesthesia parameters were collected (peak airway pressure,
systolic blood pressure, end tidal CO2). RESULTS: Laparoscopy was performed on 30
patients in AirSeal(r)-LP group without need to increase pressure above 7mmHg,
and no complication was reported. Incidence of shoulder pain was significantly
lower in the AirSeal(r)-LP group (23.3% vs. 73.3%, P<0.001). NRS shoulder pain
was significantly lower in AirSeal(r) LP group at hour 4, 8 and 24. Maximal
values of ETCO2, systolic blood pressure, and peak airway pressure were
significantly lower in AirSeal(r)-LP group. CONCLUSION: LP (7mmHg) laparoscopy
with AirSeal(r) platform allows laparoscopic surgery with less postoperative
shoulder pain. These results could facilitate the development of ambulatory
laparoscopy.
PMID- 28403973
TI - A national snapshot of the surgical management of deep infiltrating endometriosis
of the rectum and colon in France in 2015: A multicenter series of 1135 cases.
AB - OBJECTIVE: To perform a survey on the characteristics of the surgical management
of patients with deep infiltrating endometriosis of the rectum and the sigmoid
colon (DIERS) in France in 2015. METHOD: Case-series study enrolling patients
with DIERS involving muscularis, submucosa or mucosa, operated on from January
1st to December 31st 2015, in 56 healthcare facilities in France. Surgeons filled
in questionnaires concerning the number of patients, deep endometriosis
localizations, surgical route and techniques used on digestive tract, associated
surgical procedures and major complications. Data were pooled in a single
database. RESULTS: A total of 1135 patients from 56 healthcare facilities were
enrolled in the series (33 university hospitals, 4 general hospitals and 19
private hospitals). Deep endometriosis infiltrated only the rectum in 56.8% of
cases, the rectum and the sigmoid colon in 36.3% and only the sigmoid colon in
6.9%. Associated localizations involved the cecum in 6.6% of cases, small bowel
in 4.7%, bladder in 9%, and were responsible for stenosis of the ureters in 13.4%
and for hydronephrosis in 6.8%. Surgery was performed using conventional
laparoscopy in 82.2% of cases, robotic-assisted laparoscopy in 9.7% and open
surgery in 8.1%. Rectal shaving was carried out in 48.1% of cases, disc excision
in 7.3%, colorectal segmental resection in 40.4% and sigmoid colon segmental
resection in 6.4% (2 different procedures could be associated in the same
patient). Ureter resection was carried out in only 4% of cases, representing
29.6% of cases with stenosis of the ureters. Bladder resection was carried out in
6.9%. Vaginal resection and hysterectomy were performed in 33 and 14.7% of cases
respectively, while temporary stoma was used in 19.1%. Anastomotic leakage
occurred in 0.8% of cases, pelvic abscess in 3.4%, rectovaginal fistula in 2.7%,
ureter fistula in 0.7%, while 8.6% of patients either required catheterization
after recovery or had a post-voiding bladder volume superior to 100mL. According
to the surgical procedure used, the risk of rectovaginal fistula was 1.3, 3.6 and
3.9% after shaving, disc excision and segmental resection respectively. Intensive
care was required in 1.1% and blood transfusion in 2.2%. One patient died (0.1%)
after rectal shaving. CONCLUSIONS: Our 2015 survey of a large number of patients
managed for DIERS in France confirms that DIERS is far from being a rare disease.
Even in the setting of complex procedures requiring multidisciplinary teams, a
laparoscopic approach can achieve successful surgical treatment in 9 out of 10
patients with an acceptable risk of major postoperative complications.
PMID- 28403974
TI - Intended and actual use of self-medication and alternative products during
pregnancy by French women.
AB - OBJECTIVES: (i) To identify the proportion of non-pregnant women intending to use
self-medication and self-administered alternative products (dietary supplements,
essential oils and herbal teas) in the event of pregnancy, and the proportion of
pregnant women using these products. (ii) To describe women's risk perception
related to these products and the advice given by health professionals. METHODS:
A cross-sectional study was conducted. One hundred and twenty-eight women (60 non
pregnant and 68 pregnant women) responded to a self-administered questionnaire.
RESULTS: The proportion of pregnant women using self-medication was higher than
the proportion of non-pregnant women intending to use self-medication (72% vs
48%, P=0.01) and lower for the use of herbal teas (29% vs 63%, P<0.01). There
were no differences between the two groups for dietary supplements (25%) and
essential oils (18%). Non-prescribed medications were perceived as a risk by 90%
of all the women. Dietary supplements were considered as a medication by 68% of
pregnant women and 48% of non-pregnant women (P=0.04). Health professionals
provided advice for alternative products to 23% of the pregnant women, and 83% of
the non-pregnant women expressed the wish to receive advice if they became
pregnant. CONCLUSION: Health professionals should inform women, even before
pregnancy, about the safe use of medications and alternative products during
pregnancy.
PMID- 28403975
TI - [Fetoscopic laser coagulation in 200 consecutive monochorionic pregnancies with
twin-twin transfusion syndrome].
AB - OBJECTIVES: To report preoperative data, surgical characteristics, complications
and perinatal outcome of twin-twin transfusion syndrome (TTTS) managed with laser
ablation surgery, to analyze predictors of neonatal survival and to compare the
100 most recent cases with the older 100. MATERIALS AND METHODS: Observational
cohort moncentric study of 200 cases of TTTS consecutively treated with
fetoscopic laser coagulation between January 2004 and December 2014. RESULTS:
There were 49 stage I, 88 stage II, 55 stage III and eight stage IV. Median
gestation at time of laser was 20.1+/-3.0 weeks' gestation (WG) whereas median
gestation at delivery was 31.6+/-5.4 WG. Overall perinatal survival rate was
68.0% and 84.0% have one or more surviving twins. Preterm premature rupture of
membranes occurred in 39 cases with and the median gestational age for this
complication was 28.8+/-4.6 SA. Predictive factors to have at least one living
birth were Quintero stage and gestational age at delivery. In the most recent
period, there were significantly more TTTS Quintero stage I treated with laser,
more coagulation by the Solomon technique and a larger number of coagulated
vessels. CONCLUSION: The neonatal survival of TTTS is improved by fetoscopic
laser coagulation, preferely by using Solomon tecnhique. The use of active
management of stage I is currently on research.
PMID- 28403976
TI - [Fetal scalp pH during labor: Which threshold for intervention?]
AB - OBJECTIVE: In case of abnormal fetal heart rate, there is no consensus on the
decision threshold pH scalp leading to a rapid birth. The objective of this study
was to compare neonatal issues and cesarean rate in two maternity using different
decision thresholds of scalp pH. MATERIAL AND METHODS: A comparative
retrospective study conducted in two level III maternity units between January
2013 and May 2014, one maternity unit used a decision threshold of 7.20
(maternity unit 7,20), and the other one a threshold of 7.25 (maternity unit
7,25). An adverse neonatal outcome was defined by a composite endpoint of
neonatal morbidity. The risk of cesarean was assessed using a multivariate
analysis. RESULTS: One hundred and four patients were included in the maternity
unit 7,20 and 163 patients in the maternity 7,25. Adverse neonatal outcome was
similar in both maternities (25% vs. 30,1%; P=0.4). The average pH at birth was
similar in both maternities, as well as the Apgar score at 5minutes and neonatal
transfer rates. However, BE<-12 was more frequent in maternity using 7,20 scalp
pH threshold (7% vs. 0%; P<0.01). The cesarean rate was higher in maternity 7,25
(adjusted OR=2.23 95% CI [1.17-4.25]). CONCLUSION: It seems that a decisional
threshold fixed to 7,20 could be used reasonably. It could allow to reduce
cesarean rate. Other studies are, however, needed to confirm that such threshold
of 7,20 does not increase the risk of severe acidosis.
PMID- 28403977
TI - New approaches for assessing childbirth positions.
AB - BACKGROUND: An overview of labor based only on epidemiological data cannot
identify or explain the mechanisms involved in childbirth. Data about the
position that women should take in giving birth are discordant. None of the
studies of birth positions adequately define or describe them or their
biomechanical impact (pelvic orientation, position of the back). The measurement
of the effect of one position relative to that of another requires precise
definitions of each position and of their maternal biomechanical consequences, as
well as safe measurement methods. METHODOLOGY: We have developed a system to
analyze the position of labor by quantifying the posture of the woman's body
parts (including thighs, trunk, and pelvis), using an optoelectronic motion
capture device (ViconTM, Oxford Metrics) widely used in human movement analysis
and a system for measuring the lumbar curve (Epionics spine system). A specific
body model has also been created to conduct this biomechanical analysis, which is
based on external markers. With this methodology and model, it should be possible
to define: (1) the hip joint angles (flexion/extension, abduction/adduction,
internal/external rotation); (2) the ante/retroversion of the pelvis; (3) the
lumbar curve. DISCUSSION: This methodology could become a reference for assessing
delivery postures, one that makes it possible to describe the relation between
the postures used in the delivery room and their impact on the pelvis and the
spine in an integrated and comprehensive model. TRIAL REGISTRATION: No. Eudract
2013-A01203-42.
PMID- 28403978
TI - [Pelvic nodules in a young woman: All is not endometriosis!]
AB - Splenosis is a pathology resulting from a rupture of the spleen due to a trauma
or a surgery. We report the case of a patient presenting with a splenosis,
initially diagnosed as endometriosis-related pelvic nodules, the most frequent
cause of pelvic nodules in women. We will describe the imaging strategy that led
to the final diagnosis of splenosis.
PMID- 28403979
TI - Surgical procedure for a late abdominal pregnancy with complete placenta removal.
PMID- 28403981
TI - Management of the multiple symptoms of irritable bowel syndrome.
AB - Irritable bowel syndrome (IBS) is one of the most common functional
gastrointestinal disorders. A stepwise management approach is advocated for
patients with IBS. For a substantial proportion of patients with mild symptoms,
general management principles, including making a confident diagnosis and
offering explanation, reassurance, and dietary and lifestyle advice, are
sufficient. However, many patients continue to have moderate-to-severe symptoms
and are not satisfied solely with this approach. In these patients, use of
pharmacotherapy on the basis of the predominant symptom (constipation, diarrhoea,
pain, or bloating) or combination of symptoms is the next step. For patients with
symptoms that are refractory to these initial treatment options and those who
have comorbid conditions or psychological symptoms, a combination of therapies
should be used, and the use of psychotropic drugs and psychological treatment
alternatives is often effective. Finally, the key to successful treatment of
patients with IBS is a good physician-patient relationship and use of person
centred care principles.
PMID- 28403982
TI - Significance of anti-HBc alone serological status in clinical practice.
AB - Serum samples identified as positive for total anti-HBc, but negative for both
HBsAg and anti-HBs, are referred to as anti-HBc alone. This serological response
is compatible with acute, resolved, and chronic hepatitis B virus (HBV)infection
but might also signify occult HBV infection. Once the anti-HBc alone pattern is
detected, false-positive reactivity should be ruled out and further analyses can
resolve the clinical status of the donor. The identification of anti-HBc
positivity in the absence of HBsAg in organ transplant donors and in candidate
patients for chemotherapy and immunosuppressive therapy requires further
investigation because of the risk of HBV reactivation. False-positive detection,
acute infection during the window phase, and resolved or chronic HBV infection
are all possible and only distinguishable if the additional assays are done and
measures of liver damage are taken into account. Measurement of serum anti-HBs
responses after the administration of HBV vaccination can be useful to
distinguish this serological profile. In view of the low risk of HBV reactivation
in anti-HBc alone patients who are candidates for immunosuppressive treatment,
such patients might not require pre-emptive antiviral therapy, but should be
followed up on a monthly basis for alanine aminotransferase followed by
quantitative HBV DNA testing in those with alanine aminotransferase increase.
According to specific guidelines, nucleoside analogue prophylaxis is recommended
in anti-HBc-positive liver allograft recipients and anti-HBc alone individuals
who receive chemotherapy or biological therapy and should be continued for 6-12
months after discontinuation of such immunosuppressive therapies to protect
against HBV reactivation.
PMID- 28403980
TI - Characteristics, management, and outcomes of patients with hepatocellular
carcinoma in Africa: a multicountry observational study from the Africa Liver
Cancer Consortium.
AB - BACKGROUND: Hepatocellular carcinoma is a leading cause of cancer-related death
in Africa, but there is still no comprehensive description of the current status
of its epidemiology in Africa. We therefore initiated an African hepatocellular
carcinoma consortium aiming to describe the clinical presentation, management,
and outcomes of patients with hepatocellular carcinoma in Africa. METHODS: We did
a multicentre, multicountry, retrospective observational cohort study, inviting
investigators from the African Network for Gastrointestinal and Liver Diseases to
participate in the consortium to develop hepatocellular carcinoma research
databases and biospecimen repositories. Participating institutions were from
Cameroon, Egypt, Ethiopia, Ghana, Ivory Coast, Nigeria, Sudan, Tanzania, and
Uganda. Clinical information-demographic characteristics, cause of disease, liver
related blood tests, tumour characteristics, treatments, last follow-up date, and
survival status-for patients diagnosed with hepatocellular carcinoma between Aug
1, 2006, and April 1, 2016, were extracted from medical records by participating
investigators. Because patients from Egypt showed differences in characteristics
compared with patients from the other countries, we divided patients into two
groups for analysis; Egypt versus other African countries. We undertook a
multifactorial analysis using the Cox proportional hazards model to identify
factors affecting survival (assessed from the time of diagnosis to last known
follow-up or death). FINDINGS: We obtained information for 2566 patients at 21
tertiary referral centres (two in Egypt, nine in Nigeria, four in Ghana, and one
each in the Ivory Coast, Cameroon, Sudan, Ethiopia, Tanzania, and Uganda). 1251
patients were from Egypt and 1315 were from the other African countries (491 from
Ghana, 363 from Nigeria, 277 from Ivory Coast, 59 from Cameroon, 51 from Sudan,
33 from Ethiopia, 21 from Tanzania, and 20 from Uganda). The median age at which
hepatocellular carcinoma was diagnosed significantly later in Egypt than the
other African countries (58 years [IQR 53-63] vs 46 years [36-58]; p<0.0001).
Hepatitis C virus was the leading cause of hepatocellular carcinoma in Egypt
(1054 [84%] of 1251 patients), and hepatitis B virus was the leading cause in the
other African countries (597 [55%] of 1082 patients). Substantially fewer
patients received treatment specifically for hepatocellular carcinoma in the
other African countries than in Egypt (43 [3%] of 1315 vs 956 [76%] of 1251;
p<0.0001). Among patients with survival information (605 [48%] of 1251 in Egypt
and 583 [44%] of 1315 in other African countries), median survival was shorter in
the other African countries than in Egypt (2.5 months [95% CI 2.0-3.1] vs 10.9
months [9.6-12.0]; p<0.0001). Factors independently associated with poor survival
were: being from an African countries other than Egypt (hazard ratio [HR] 1.59
[95% CI 1.13-2.20]; p=0.01), hepatic encephalopathy (2.81 [1.72-4.42]; p=0.0004),
diameter of the largest tumour (1.07 per cm increase [1.04-1.11]; p<0.0001), log
alpha-fetoprotein (1.10 per unit increase [1.02-1.20]; p=0.0188), Eastern
Cooperative Oncology Group performance status 3-4 (2.92 [2.13-3.93]; p<0.0001)
and no treatment (1.79 [1.44-2.22]; p<0.0001). INTERPRETATION: Characteristics of
hepatocellular carcinoma differ between Egypt and other African countries. The
proportion of patients receiving specific treatment in other African countries
was low and their outcomes were extremely poor. Urgent efforts are needed to
develop health policy strategies to decrease the burden of hepatocellular
carcinoma in Africa. FUNDING: None.
PMID- 28403983
TI - The role of the gut microbiota in sepsis.
AB - For decades, the gut was thought to play an important role in sepsis
pathogenesis. Sepsis is defined as life-threatening organ dysfunction caused by a
dysregulated host response to infection. Organ failure assessment for sepsis
focuses on respiratory, cardiovascular, hepatic, renal, neurological, and
haematological systems. Unfortunately, symptoms of gut failure are non-specific
and are therefore not assessed. The composition of the intestinal microbiome,
however, is affected by sepsis, and might contribute to the development of organ
failure. Experimental work underscores the role of the microbiota in maintaining
gut-barrier function, and modulation of the innate and adaptive immune system.
Translation of these preclinical findings into functional characterisations will
be essential to understand how disruption of commensals affects susceptibility
and outcome of sepsis. In this Review, we identify knowledge gaps which, if
addressed, will help researchers understand the role of the microbiota in sepsis,
and provide microbiota-targeted tools to improve sepsis management.
PMID- 28403984
TI - Elastosis perforans serpiginosa in a patient with Wilson's disease.
PMID- 28403985
TI - Pancreatic cancer: how can we tackle the lack of progress?
PMID- 28403986
TI - Direct oral anticoagulants and gastroenterologists.
PMID- 28403987
TI - Terlipressin for hepatorenal syndrome: ready for prime time.
PMID- 28403988
TI - Liver cancer in Africa: untold aspects of an acknowledged scourge.
PMID- 28403989
TI - Hepatitis C treatment and liver cancer recurrence: cause for concern?
PMID- 28403990
TI - A plea for TDM-based optimisation for treatment of Crohn's disease.
PMID- 28403991
TI - A plea for TDM-based optimisation for treatment of Crohn's disease - Authors'
reply.
PMID- 28403994
TI - Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic
review and network meta-analysis.
AB - BACKGROUND: Direct oral anticoagulants are increasingly used for a wide range of
indications. However, data are conflicting about the risk of major
gastrointestinal bleeding with these drugs. We compared the risk of
gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low
molecular-weight heparin. METHODS: For this systematic review and meta-analysis,
we searched MEDLINE and Embase from database inception to April 1, 2016, for
prospective and retrospective studies that reported the risk of gastrointestinal
bleeding with use of a direct oral anticoagulant compared with warfarin or low
molecular-weight heparin for all indications. We also searched the Cochrane
Library for systematic reviews and assessment evaluations, the National Health
Service (UK) Economic Evaluation Database, and ISI Web of Science for conference
abstracts and proceedings (up to April 1, 2016). The primary outcome was the
incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding
as a secondary outcome. We did a Bayesian network meta-analysis to produce
incidence rate ratios (IRRs) with 95% credible intervals (CrIs). FINDINGS: We
identified 38 eligible articles, of which 31 were included in the primary
analysis, including 287 692 patients exposed to 230 090 years of anticoagulant
drugs. The risk of major gastrointestinal bleeding with direct oral
anticoagulants did not differ from that with warfarin or low-molecular-weight
heparin (factor Xa vs warfarin IRR 0.78 [95% CrI 0.47-1.08]; warfarin vs
dabigatran 0.88 [0.59-1.36]; factor Xa vs low-molecular-weight heparin 1.02 [0.42
2.70]; and low-molecular-weight heparin vs dabigatran 0.67 [0.20-1.82]). In the
secondary analysis, factor Xa inhibitors were associated with a reduced risk of
all severities of gastrointestinal bleeding compared with warfarin (0.25 [0.07
0.76]) or dabigatran (0.24 [0.07-0.77]). INTERPRETATION: Our findings show no
increase in risk of major gastrointestinal bleeding with direct oral
anticoagulants compared with warfarin or low-molecular-weight heparin. These
findings support the continued use of direct oral anticoagulants. FUNDING: Leeds
Teaching Hospitals Charitable Foundation.
PMID- 28403996
TI - Perpetuating the sameness of American and British spellings.
PMID- 28403995
TI - Comparative efficacy of pharmacological strategies for management of type 1
hepatorenal syndrome: a systematic review and network meta-analysis.
AB - BACKGROUND: Several drugs have been studied to improve outcomes for patients with
hepatorenal syndrome, but trials have reported variable efficacy. We aimed to
compare the efficacy of different management strategies for type 1 hepatorenal
syndrome. METHODS: For this systematic review and network meta-analysis, we
searched Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE,
Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Scopus, and Web
of Science for papers published up to June 9, 2016. We selected randomised
controlled trials of adults (>18 years) with decompensated cirrhosis and type 1
hepatorenal syndrome that compared the efficacy of active vasoactive drugs
(terlipressin, midodrine, octreotide, noradrenaline, and dopamine; alone or in
combination) with placebo or each other. The primary outcome was reduction in
short-term mortality. Secondary outcomes were reversal of hepatorenal syndrome,
relapse of hepatorenal syndrome after initial reversal, and adverse events. We
did pairwise and network meta-analyses to produce odds ratios (ORs) and 95% CIs.
We used the GRADE criteria to appraise quality of evidence. FINDINGS: We
identified 13 randomised controlled trials done in 739 adults with type 1
hepatorenal syndrome. All participants received supportive therapy with albumin.
Moderate-quality evidence might support the use of terlipressin over placebo for
reduction of short-term mortality (OR 0.65, 95% CI 0.41-1.05), whereas only low
quality evidence supported the use of noradrenaline, midodrine plus octreotide,
and dopamine plus furosemide over placebo to reduce mortality, and no ORs for any
of the comparisons versus placebo were significant. Moderate-quality evidence
supported the use of terlipressin over midodrine plus octreotide (OR 26.25, 95%
CI 3.07-224.21) to reverse hepatorenal syndrome, with low-quality evidence
supporting the use of noradrenaline over placebo (4.17, 1.37-12.50) and over
midodrine plus octreotide (10.00, 1.49-50.00) for this outcome. A median of 16%
(range 5-20) of terlipressin-treated patients, and 33% (range 6-40) noradrenaline
treated patients with reversal of hepatorenal syndrome had recurrence on
discontinuation of therapy. A median of 8% (range 4-22) terlipressin-treated
patients required discontinuation of therapy due to serious adverse events.
INTERPRETATION: Terlipressin with albumin might reduce short-term mortality
compared with placebo in patients with type 1 hepatorenal syndrome. Terlipressin
with albumin and noradrenaline with albumin are both superior to midodrine plus
octreotide with albumin for reversal of hepatorenal syndrome. Pragmatic clinical
trials of terlipressin with albumin are warranted to evaluate real-world
effectiveness and safety in patients with type 1 hepatorenal syndrome. FUNDING:
None.
PMID- 28403997
TI - Circulatory, respiratory and behavioral responses in isoflurane anesthetized
llamas.
AB - OBJECTIVES: To evaluate the circulatory, respiratory and behavioral effects of
isoflurane (ISO) anesthesia in llamas during mechanical ventilation and
spontaneous breathing. DESIGN: Prospective randomised study. ANIMAL: Six adult,
neutered male llamas (10 +/- 1 years [mean +/- SD], 179 +/- 32 kg). MATERIALS AND
METHODS: Animals in which the minimum alveolar concentration (MAC) had been
previously determined were anesthetized with ISO in oxygen. Inspired and end
tidal (ET) ISO were sampled continuously. Arterial blood pH, respiratory and
circulatory variables, and clinical signs of anesthesia were recorded at three
doses (1.0, 1.5 and 2.0 times the individual animal's MAC; mean MAC value 1.13%)
of ISO during spontaneous and controlled ventilation. A series of Latin squares
was used to determine order of dose. Controlled ventilation (CV) (target PaCO2 38
+/- 5 mm Hg [5.0 +/- 0.6 kPa]) preceded spontaneous ventilation (SV) at each
dose. Animals breathed spontaneously for approximately 10 minutes prior to data
collection. Body temperature was maintained at 37 +/- 0.6 degrees C. Circulatory
and respiratory data were analysed with a mixed model, least squares analysis of
variance, for repeated measures taken at equally spaced intervals. p < 0.05.
RESULTS: Dose and mode of ventilation had significant influences on measured
variables. For example, heart rate increased as dose increased; 67 +/- 14 beats
minute-1 at 1.0 MAC-CV versus 77 +/- 6 beats minute-1 at 2 MAC-CV. Conversely,
mean arterial pressure decreased with increasing dose; 82 +/- 13 mm Hg at MAC-CV
versus 52 +/- 15 mm Hg at 2 MAC-CV. Arterial CO2 increased with increasing dose
during SV; 45 +/- 5 mm Hg [6 +/- 0.6 kPa] at MAC versus 53 +/- 4 mmHg [7 +/- 0.5
kPa] at 2 MAC. Reflex activity (e.g. palpebral reflex) and muscle tone (e.g. jaw
tone) decreased while eyelid aperture increased with increasing anesthetic dose.
CONCLUSIONS AND CLINICAL RELEVANCE: The influence of ISO dose and mode of
ventilation on circulatory and respiratory variables in llamas is qualitatively
similar to that reported in other species. Changes in reflex activity and muscle
tone may be used to guide appropriate anesthetic delivery in ISO-induced llamas.
PMID- 28403998
TI - Assessment of ketamine/medetomidine anaesthesia in the New Zealand White rabbit.
AB - OBJECTIVE: To compare the characteristics of anaesthesia induced with four dose
combinations of ketamine/medetomidine. DESIGN: Prospective randomized study.
Animals Five female New Zealand White (NZW) rabbits of approximately 2.3 kg.
METHODS: Rabbits were given one of four drug combinations (25/0.25; 15/0.5;
15/0.25 and 10/0.5 mg kg-1 IM) on four successive occasions with a four day
interval. Response to injection and then arterial blood gas and cardiovascular
parameters were recorded at predetermined time points. Toe and ear pinch reflexes
gave measures of total duration of surgical anaesthesia and total sleep time.
Analyses used repeated measures analysis of variance. RESULTS: Induction was
smooth with little reaction to injection and intubation achieved easily. Two
combinations (15/0.25, 10/0.5) produced moderate hypoxaemia (mean pO2 < 8.0 kPa)
and two (25/0.25, 15/0.5) very marked hypoxaemia (mean pO2 < 5.3 kPa). This was
reversed within 15 minutes of oxygen administration and all rabbits recovered
uneventfully. Heart rates fell in all cases, with only minimal effects on
arterial blood pressure and no cardiac arrhythmias. Mean duration of surgical
anaesthesia was significantly longer for dose groups 25/0.25 (57 +/- 12 minutes)
and 15/0.5 (59 +/- 17 minutes, p = 0.01) compared to dose group 15/0.25 (27 +/- 8
minutes). Only three animals in the 10/0.5 mg kg-1 group achieved surgical
anaesthesia. Mean duration of loss of the ear pinch reflex was similar between
doses, being, respectively, 64 +/- 13, 81 +/- 7, 60 +/- 22 and 62 +/- 24 minutes.
Sleep time was significantly longer for the 15/0.5 dose (112 +/- 10 minutes)
compared to 15/0.25 (86 +/- 22 minutes, p = 0.04). Sleep times for the 25/0.25
and 10/0.5 mg kg-1 doses were, respectively, 103 +/- 23 and 108 +/- 12 minutes.
CONCLUSIONS: Ketamine/medetomidine reliably produces smooth induction and
recovery in the NZW rabbit, but due to the degree of hypoxaemia produced, should
only be used with simultaneous provision of oxygen. CLINICAL RELEVANCE: Currently
recommended dose rates of ketamine/medetomidine for minor procedures such as
ovariohysterectomy in rabbits (25 mg/0.5 mg kg-1) are unnecessarily high; a dose
of 15/0.25 mg kg-1 should be adequate for 15-30 minutes of surgical anaesthesia.
PMID- 28403999
TI - An evaluation of apnea or spontaneous ventilation in early recovery following
mechanical ventilation in the anesthetized horse.
AB - OBJECTIVE: To compare arterial oxygen and carbon dioxide tensions in apneic and
spontaneously ventilating horses recovering from anesthesia. STUDY DESIGN:
Randomized clinical trial. ANIMAL POPULATION: Forty-two healthy horses averaging
466 +/- 106 kg and 6 +/- 5 years of age. METHODS: Anesthetized horses undergoing
a variety of surgical procedures and receiving positive pressure ventilation
(IPPV) were divided into two equal groups. One group was allowed to return to
spontaneous ventilation prior to disconnection from the anesthetic circuit
(weaned). The other group remained apneic during transport to a recovery stall.
Arterial blood gas data were collected at five time points: 20 minutes before
moving to a recovery stall (t = - 20); at the time the anesthetic circuit was
disconncted (t = 0); at 3 and 5 minutes post-disconnection (t = 3 and t = 5) and
at the time of the first spontaneous breath (t = sv). The data were analyzed
using an anova method for repeated measures and paired, two-tailed t-tests.
Significance was assumed when p < 0.05. RESULTS: The apneic group took a mean of
5 minutes 18 seconds (+/- 135 seconds) before starting spontaneous ventilation.
This group maintained significantly higher PaO2 levels at intermediate time
points (t = 0 and t = 3) but no difference was noted after 5 minutes. PaCO2
levels were higher in the weaned group at time 0 minutes, returning to a
comparable level to the apneic group at t = 3 minutes. CONCLUSIONS AND CLINICAL
RELEVANCE: Horses can survive a short period of apnea during transport from the
surgery suite to recovery stall and may benefit from a reduced incidence of
transient hypoxemia compared with spontaneously ventilating horses. This
information has practical implications for the anesthetist evaluating the options
for discontinuing IPPV when horses are moved to a recovery stall.
PMID- 28404000
TI - Pulsed delivery of nitric oxide counteracts hypoxaemia in the anaesthetized
horse.
AB - OBJECTIVE: To study the effect of the pulsed delivery of nitric oxide (NO) on
pulmonary gas exchange in the anaesthetized horses. Design Prospective,
controlled randomized. ANIMALS: Five healthy Standardbred trotters, three
geldings and two mares. METHODS: The horses were anaesthetized with thiopentone
and isoflurane and positioned in dorsal recumbency. Nitric oxide was added as a
pulse to the inspired gas during the first half of each inspiration. In three
horses the effect of NO on the ventilation-perfusion distribution was also
investigated using the multiple inert gas elimination technique. Data were
analysed with repeated measures ANOVA. RESULTS: During spontaneous breathing,
arterial oxygen tension (PaO2) increased with NO inhalation, from 14 +/- 2 to 29
+/- 3 kPa (105 +/- 15 to 218 +/- 23 mm Hg) (p < 0.001). Arterial oxygen tension
also increased, from 17 +/- 3 to 31 +/- 5 kPa (128 +/- 23 to 233 +/- 38 mm Hg) (p
< 0.05) during intermittent positive pressure ventilation. The increase in PaO2
was mainly due to a reduced right to left vascular shunt, but ventilation and
perfusion matching also improved. The beneficial effect of NO inhalation was lost
within 5 minutes of its discontinuation. CONCLUSION: Delivery of NO as a pulse
during inspiration is an effective method for counteracting impaired gas exchange
caused by anaesthesia in horses. Pulsation has to be continuous because of the
transience of NO's therapeutic effect. CLINICAL RELEVANCE: Horses with impaired
pulmonary gas exchange during anaesthesia can be treated with pulsed NO
inhalation.
PMID- 28404001
TI - The effects of maternal plasma dobutamine levels on fetal oxygenation in
anaesthetized sheep.
AB - OBJECTIVE: To measure the effects of dobutamine infusion on fetal oxygenation
during isoflurane anaesthesia in pregnant ewes. STUDY DESIGN: Prospective
randomized experimental study. ANIMALS: Seven clinically normal adult pregnant
Rambouillet-Dorset cross ewes with fetuses of 117-122 days gestational age.
METHODS: The ewes were anaesthetized with ketamine (2 mg kg-1) IM, and isoflurane
(FE'ISO 2.0%) in oxygen. After instrumentation and stabilization, dobutamine was
infused at 4 ug kg-1minute-1 for 60 minutes and 10 ug kg-1minute-1 for 60 minutes
in random order, separated by a 20-minute washout period. Catheters were placed
in the maternal and fetal carotid arteries; these were used for continuous blood
pressure measurement and intermittent blood sampling. RESULTS: Maternal mean
systemic carotid arterial pressure was 60 mm Hg prior to dobutamine infusion.
After 5 minutes of dobutamine infusion, fetal oxygen saturation increased (p <
0.05) from 0.62 (0.17-0.71, minimum-maximum) to 0.72 (0.28-0.78) at a dose of 4
ug kg-1minute-1 and to 0.70 (0.20-0.73) at a dose of 10 ug kg-1minute-1. These
increases were maintained during the infusion and were not significantly
different between doses. Maternal oxygen saturation remained constant at 1.0
before and during all infusions. Although maternal heart rate and blood pressure
increased (p < 0.05) by 90% and 25%, respectively, with dobutamine, this
stimulant effect was not evident in the corresponding fetal variables. Maternal
haemoglobin concentration increased 30% (p < 0.05) with each infusion.
CONCLUSIONS: Dobutamine at 4 ug kg-1minute-1 increases fetal oxygenation that is
not improved by a dose of 10 ug kg-1minute-1. This increase is largely due to an
increase in maternal haemoglobin concentration that, in turn, increases oxygen
delivery to the placenta. CLINICAL RELEVANCE: The use of dobutamine to treat
hypotension in pregnant sheep during isoflurane anaesthesia improves fetal
oxygenation. This may be true in other species.
PMID- 28404002
TI - Comparison of diazepam-ketamine and thiopentone for induction of anaesthesia in
healthy dogs.
AB - OBJECTIVE: To compare the anaesthetic and cardiopulmonary effects of a diazepam
ketamine combination with thiopentone for induction of anaesthesia in dogs.
ANIMAL POPULATION: Twenty healthy dogs of various breeds weighing between 3.8 and
42.6 kg undergoing major orthopaedic or soft tissue surgery. MATERIALS AND
METHODS: Pre-anaesthetic medication in all cases was intramuscular acepromazine
and methadone given 30 minutes before induction of anaesthesia. Each animal was
then randomly assigned to receive either thiopentone or diazepam and ketamine.
Quality of conditions for, and time to tracheal intubation were recorded.
Anaesthesia was maintained with halothane in oxygen and nitrous oxide. Heart
rate, respiratory rate, systolic blood pressure, end tidal carbon dioxide
tensions and oxygen saturation were recorded at 10 minute intervals throughout
surgery. The quality of recovery from anaesthesia was assessed. RESULTS: The
quality of induction in both groups was satisfactory. The total mean time (+/-
SD) to tracheal intubation (162 +/- 84 seconds) was significantly longer in dogs
receiving diazepam and ketamine compared to dogs receiving thiopentone (62 +/- 28
seconds). Heart rate, systolic blood pressure and end tidal carbon dioxide
concentration were not significantly different between groups. Respiratory rate
was significantly higher in the diazepam-ketamine group between 0 and 30 minutes.
The quality of recovery was similar in each group. CONCLUSIONS: There appear to
be fewer differences between the induction agents examined in this study than was
previously believed. No pressor, or other cardiovascular stimulating effects were
detected in the dogs that received diazepam and ketamine. CLINICAL RELEVANCE: The
absence of obvious differences between groups suggests that pre-anaesthetic
medication, inhaled anaesthetics and the physiological effects of surgery itself
probably had a greater effect on the variables studied than the induction agent
used. Further studies are required to determine whether diazepam and ketamine
offers significant advantages over other induction agents in the unhealthy dog.
PMID- 28404003
TI - Sedative-hypnotic effects of midazolam in goats after intravenous and
intramuscular administration.
AB - OBJECTIVE: To examine the effect of dose and route of administration on the
sedative-hypnotic effects of midazolam. DESIGN: Prospective randomized controlled
study ANIMALS: Six indigenous, African bred goats. METHODS: Pilot studies
indicated that the optimum dose of midazolam for producing sedation was 0.6 mg kg
1 for intramuscular (IM) injection, while the optimum intravenous (IV) doses
causing hypnosis without, and with loss of palpebral reflexes were 0.6 mg kg-1
and 1.2 mg kg-1, respectively. These doses and routes of administration were
compared with a saline placebo in a randomized block design in the main
experiment, and the sedative-hypnotic effects evaluated according to pre
determined scales. RESULTS: Intramuscular midazolam produced sedation with or
without sternal recumbency in all animals with the peak effect occurring 20
minutes after administration. The scores for IM sedation with midazolam were
significantly different (p < 0.05) from placebo. Intravenous midazolam at 0.6 mg
kg-1 resulted in hypnosis, and at 1.2 mg kg-1 increased reflex suppression was
observed. The maximum scores for hypnosis at both doses were obtained 5 minutes
after IV injection. The mean (+/- SD) duration of lateral recumbency was 10.8 (+/
3.8) minutes after IV midazolam (0.6 mg kg-1) compared to 20 (+/- 5.2) minutes
after midazolam at 1.2 mg kg-1. Compared to baseline, the heart rate increased
significantly (p < 0.05) after high dose IV midazolam. CONCLUSION: Intramuscular
midazolam (0.6 mg kg-1) produced maximum sedation 20 minutes after injection.
Intravenous injection produced maximum hypnosis within 5 minutes. Increasing the
IV dose from 0.6 to 1.2 mg kg-1 resulted in increased reflex suppression and
duration of hypnosis. CLINICAL RELEVANCE: For a profound effect with rapid onset
midazolam should be given IV in doses between 0.6 and 1.2 mg kg-1.
PMID- 28404004
TI - Cardiac arrhythmias associated with acute major haemorrhage during craniectomy in
a dog.
AB - An estimated 43% of total blood volume was lost during craniectomy in a 32-kg
Labrador retriever. One episode of bradycardia, followed by ventricular
tachycardia occurred during surgery when the rate of haemorrhage exceeded fluid
replacement. Sinus rhythm was re-established with intravenous lidocaine (1.25 mg
kg-1). Twenty-four hours later, premature ventricular complexes appeared followed
by episodes of ventricular tachycardia, some requiring lidocaine treatment.
Myocardial hypoxia resulting either from hypovolaemia and/or air embolism (the
right transverse venous sinus was damaged during surgery) may have caused the
arrhythmias. Mild intracranial hypertension may have aggravated the problem.
PMID- 28404005
TI - Access to HCV treatments: hurdles not barriers.
PMID- 28404008
TI - Surgery versus conservative management for recurrent and ongoing left-sided
diverticulitis (DIRECT trial): an open-label, multicentre, randomised controlled
trial.
AB - BACKGROUND: Patients with recurrent or persisting complaints after an episode of
left-sided diverticulitis are managed with either conservative measures or
elective sigmoidectomy. To date, there are no data from randomised trials. We
aimed to establish which treatment leads to a better quality of life for patients
with diverticulitis. METHODS: We did an open-label, multicentre, randomised
controlled trial (DIRECT trial) in 24 teaching and two academic hospitals in the
Netherlands. Patients aged 18-75 years presenting with either recurrent (three or
more presentations with clinical signs of acute diverticulitis within 2 years) or
persistent abdominal complaints (ongoing lower left abdominal pain or persistent
change in bowel habits for >=3 months) after an episode of left-sided
diverticulitis, confirmed by CT, ultrasound, or endoscopy, were included.
Patients were excluded if they had previous elective or emergency surgery for
acute sigmoid diverticulitis, an absolute operation indication, suspicion of a
colorectal malignancy, with a preoperative or postoperative risk greater than III
(on the American Society of Anesthesiologists classification), or were unable to
complete questionnaire or follow-up. Patients were randomly assigned (3:3) to
receive conservative management or elective (laparoscopic) sigmoidectomy using a
digital randomisation system, stratified by type of disease and centre, with a
block size of six. Patients, physicians, and researchers were not masked to
treatment allocation. Our primary endpoint was health-related quality of life,
measured by the Gastrointestinal Quality of Life Index (GIQLI) at 6 months after
inclusion or surgery, depending on randomisation group. This trial is registered
with trialregister.nl, number NTR1478, and is closed for inclusion. FINDINGS:
Between July 1, 2010, and April 1, 2014, we randomly assigned 109 patients to
receive surgical treatment (resection; n=53) or conservative management (n=56),
after which the Data Safety and Monitoring Board prematurely terminated the trial
because of increasing difficulties in recruitment. 47 (89%) of 53 patients
received surgical treatment and 43 (77%) of 56 patients received conservative
management. The GIQLI score at 6 months' follow-up was significantly higher in
patients randomly assigned to receive surgical treatment (mean 114.4 [SD 22.3])
than conservative management (100.4 [22.7]; mean difference 14.2, 95% CI 7.2
21.1, p<0.0001). 43 (38%) of 109 patients had a severe adverse event in the first
6 months after treatment (18 [34%] of 53 patients in the surgical treatment group
vs 23 [40%] of 57 patients in the conservative treatment group). Seven (15%)
patients who received surgical treatment developed anastomotic leakage. Of the 56
patients assigned to be treated conservatively, 13 (23%) ultimately underwent
elective resection due to ongoing abdominal complaints, with no anastomotic
leakage. We recorded no patient deaths. INTERPRETATION: Elective sigmoidectomy,
despite its inherent risk of complications, results in better quality of life
than conservative management in patients with recurrent and persisting abdominal
complaints after an episode of diverticulitis. FUNDING: Netherlands Organisation
for Health Research and Development.
PMID- 28404009
TI - When is elective resection after acute diverticulitis reasonable?
PMID- 28404011
TI - Cytosponge use in risk stratification of Barrett's oesophagus.
PMID- 28404010
TI - Risk stratification of Barrett's oesophagus using a non-endoscopic sampling
method coupled with a biomarker panel: a cohort study.
AB - BACKGROUND: Barrett's oesophagus predisposes to adenocarcinoma. However, most
patients with Barrett's oesophagus will not progress and endoscopic surveillance
is invasive, expensive, and fraught by issues of sampling bias and the subjective
assessment of dysplasia. We investigated whether a non-endoscopic device, the
Cytosponge, could be coupled with clinical and molecular biomarkers to identify a
group of patients with low risk of progression suitable for non-endoscopic follow
up. METHODS: In this multicentre cohort study (BEST2), patients with Barrett's
oesophagus underwent the Cytosponge test before their surveillance endoscopy. We
collected clinical and demographic data and tested Cytosponge samples for a
molecular biomarker panel including three protein biomarkers (P53, c-Myc, and
Aurora kinase A), two methylation markers (MYOD1 and RUNX3), glandular atypia,
and TP53 mutation status. We used a multivariable logistic regression model to
compute the conditional probability of dysplasia status. We selected a simple
model with high classification accuracy and applied it to an independent
validation cohort. The BEST2 study is registered with ISRCTN, number 12730505.
FINDINGS: The discovery cohort consisted of 468 patients with Barrett's
oesophagus and intestinal metaplasia. Of these, 376 had no dysplasia and 22 had
high-grade dysplasia or intramucosal adenocarcinoma. In the discovery cohort, a
model with high classification accuracy consisted of glandular atypia, P53
abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to
hip ratio, and length of the Barrett's oesophagus segment. 162 (35%) of 468 of
patients fell into the low-risk category and the probability of being a true non
dysplastic patient was 100% (99% CI 96-100) and the probability of having high
grade dysplasia or intramucosal adenocarcinoma was 0% (0-4). 238 (51%) of
participants were classified as of moderate risk; the probability of having high
grade dysplasia was 14% (9-21). 58 (12%) of participants were classified as high
risk; the probability of having non-dysplastic endoscopic biopsies was 13% (5
27), whereas the probability of having high-grade dysplasia or intramucosal
adenocarcinoma was 87% (73-95). In the validation cohort (65 patients), 51 were
non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65
patients were classified as being low-risk, and the probability of being non
dysplastic was 96.0% (99% CI 73.80-99.99). The moderate-risk group comprised 27
non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group
(8% of the cohort) had no non-dysplastic cases and five patients with high-grade
dysplasia. INTERPRETATION: A combination of biomarker assays from a single
Cytosponge sample can be used to determine a group of patients at low risk of
progression, for whom endoscopy could be avoided. This strategy could help to
avoid overdiagnosis and overtreatment in patients with Barrett's oesophagus.
FUNDING: Cancer Research UK.
PMID- 28404013
TI - The microbiome as a potential biomarker for oesophageal adenocarcinoma.
PMID- 28404012
TI - A non-endoscopic device to sample the oesophageal microbiota: a case-control
study.
AB - BACKGROUND: The strongest risk factor for oesophageal adenocarcinoma is reflux
disease, and the rising incidence of this coincides with the eradication of
Helicobacter pylori, both of which might alter the oesophageal microbiota. We
aimed to profile the microbiota at different stages of Barrett's carcinogenesis
and investigate the Cytosponge as a minimally invasive tool for sampling the
oesophageal microbiota. METHODS: In this case-control study, 16S rRNA gene
amplicon sequencing was done on 210 oesophageal samples from 86 patients
representing the Barrett's oesophagus progression sequence (normal squamous
controls [n=20], non-dysplastic [n=24] and dysplastic Barrett's oesophagus
[n=23], and oesophageal adenocarcinoma [n=19]), relevant negative controls, and
replicates on the Illumina MiSeq platform. Samples were taken from patients
enrolled in the BEST2 study at five UK hospitals and the OCCAMS study at six UK
hospitals. We compared fresh frozen tissue, fresh frozen endoscopic brushings,
and the Cytosponge device for microbial DNA yield (qPCR), diversity, and
community composition. FINDINGS: There was decreased microbial diversity in
oesophageal adenocarcinoma tissue compared with tissue from healthy control
patients as measured by the observed operational taxonomic unit (OTU) richness
(p=0.0012), Chao estimated total richness (p=0.0004), and Shannon diversity index
(p=0.0075). Lactobacillus fermentum was enriched in oesophageal adenocarcinoma
(p=0.028), and lactic acid bacteria dominated the microenvironment in seven (47%)
of 15 cases of oesophageal adenocarcinoma. Comparison of oesophageal sampling
methods showed that the Cytosponge yielded more than ten-times higher quantities
of microbial DNA than did endoscopic brushes or biopsies using quantitative PCR
(p<0.0001). The Cytosponge samples contained the majority of taxa detected in
biopsy and brush samples, but were enriched for genera from the oral cavity and
stomach, including Fusobacterium, Megasphaera, Campylobacter, Capnocytophaga, and
Dialister. The Cytosponge detected decreased microbial diversity in patients with
high-grade dysplasia in comparison to control patients, as measured by the
observed OTU richness (p=0.0147), Chao estimated total richness (p=0.023), and
Shannon diversity index (p=0.0085). INTERPRETATION: Alterations in microbial
communities occur in the lower oesophagus in Barrett's carcinogenesis, which can
be detected at the pre-invasive stage of high-grade dysplasia with the novel
Cytosponge device. Our findings are potentially applicable to early disease
detection, and future test development should focus on longitudinal sampling of
the microbiota to monitor for changes in microbial diversity in a larger cohort
of patients. FUNDING: Cancer Research UK, National Institute for Health Research,
Medical Research Council, Wellcome Trust, The Scottish Government (RESAS).
PMID- 28404014
TI - Incidence and enteral feed antecedents of severe neonatal necrotising
enterocolitis across neonatal networks in England, 2012-13: a whole-population
surveillance study.
AB - BACKGROUND: Necrotising enterocolitis is a neonatal gastrointestinal inflammatory
disease with high mortality and severe morbidity. This disorder is growing in
global relevance as birth rates and survival of babies with low gestational age
improve. Population data are scant and pathogenesis is incompletely understood,
but enteral feed exposures are believed to affect risk. We aimed to quantify the
national incidence of severe necrotising enterocolitis, describe variation across
neonatal networks, and investigate enteral feeding-related antecedents of severe
necrotising enterocolitis. METHODS: We undertook a 2-year national surveillance
study (the UK Neonatal Collaborative Necrotising Enterocolitis [UKNC-NEC] Study)
of babies born in England to quantify the burden of severe or fatal necrotising
enterocolitis confirmed by laparotomy, leading to death, or both. Data on all
liveborn babies admitted to neonatal units between Jan 1, 2012, and Dec 31, 2013,
were obtained from the National Neonatal Research Database. In the subgroup of
babies born before a gestational age of 32 weeks, we did a propensity score
analysis of the effect of feeding in the first 14 postnatal days with own
mother's milk, with or without human donor milk and avoidance of bovine-origin
formula, or milk fortifier, on the risk of developing necrotising enterocolitis.
FINDINGS: During the study period, 118 073 babies were admitted to 163 neonatal
units across 23 networks, of whom 14 678 were born before a gestational age of 32
weeks. Overall, 531 (0.4%) babies developed severe necrotising enterocolitis, of
whom 247 (46.5%) died (139 after laparotomy). 462 (3.2%) of 14 678 babies born
before a gestational age of 32 weeks developed severe necrotising enterocolitis,
of whom 222 (48.1%) died. Among babies born before a gestational age of 32 weeks,
the adjusted network incidence of necrotising enterocolitis ranged from 2.51%
(95% CI 1.13-3.60) to 3.85% (2.37-5.33), with no unusual variation from the
adjusted national incidence of 3.13% (2.85-3.42), despite variation in feeding
practices. The absolute risk difference for babies born before a gestational age
of 32 weeks who received their own mother's milk within 7 days of birth was
0.88% (95% CI -1.15 to -0.61; relative risk 0.69, 95% CI 0.60 to 0.78; number
needed to treat to prevent one case of necrotising enterocolitis 114, 95% CI 87
to 136). For babies who received no compared with any bovine-origin products
within 14 days of birth, the absolute risk difference was -0.65% (-1.01 to -0.29;
relative risk 0.61, 0.39 to 0.83; number needed to treat 154, 99 to 345). We were
unable to assess the effect of human donor milk as use was low. INTERPRETATION:
Early feeding of babies with their own mother's milk and avoidance of bovine
origin products might reduce the risk of necrotising enterocolitis, but the
absolute reduction is small. Owing to the rarity of severe necrotising
enterocolitis, international collaborations are needed for adequately powered
preventive trials. FUNDING: National Institute for Health Research.
PMID- 28404016
TI - Necrotising enterocolitis: better data, still many questions.
PMID- 28404015
TI - Management of hepatitis C virus infection in the Asia-Pacific region: an update.
AB - The Asia-Pacific region has disparate hepatitis C virus (HCV) epidemiology, with
prevalence ranging from 0.1% to 4.7%, and a unique genotype distribution.
Genotype 1b dominates in east Asia, whereas in south Asia and southeast Asia
genotype 3 dominates, and in Indochina (Vietnam, Cambodia, and Laos), genotype 6
is most common. Often, availability of all-oral direct-acting antivirals (DAAs)
is delayed because of differing regulatory requirements. Ideally, for genotype 1
infections, sofosbuvir plus ledipasvir, sofosbuvir plus daclatasvir, or
ombitasvir, paritaprevir, and ritonavir plus dasabuvir are suitable. Asunaprevir
plus daclatasvir is appropriate for compensated genotype 1b HCV if baseline NS5A
mutations are absent. For genotype 3 infections, sofosbuvir plus daclatasvir for
24 weeks or sofosbuvir, daclatasvir, and ribavirin for 12 weeks are the optimal
oral therapies, particularly for patients with cirrhosis and those who are
treatment experienced, whereas sofosbuvir, pegylated interferon, and ribavirin
for 12 weeks is an alternative regimen. For genotype 6, sofosbuvir plus pegylated
interferon and ribavirin, sofosbuvir plus ledipasvir, or sofosbuvir plus
ribavirin for 12 weeks are all suitable. Pegylated interferon plus ribavirin has
been replaced by sofosbuvir plus pegylated interferon and ribavirin, and all-oral
therapies where available, but cost and affordability remain a major issue
because of the absence of universal health coverage. Few patients have been
treated because of multiple barriers to accessing care. HCV in the Asia-Pacific
region is challenging because of the disparate epidemiology, poor access to all
oral therapy because of availability, cost, or regulatory licensing. Until these
problems are addressed, the burden of disease is likely to remain high.
PMID- 28404020
TI - Correction to Lancet Gastroenterol Hepatol 2017; 2: 32-42.
PMID- 28404017
TI - DNA testing of pancreatic cyst fluid: is it ready for prime time?
AB - Pancreatic cysts are a clinical quandary in both diagnosis and management.
Although many cysts, such as pseudocysts and serous cystadenomas, are benign and
can be monitored clinically, mucinous cysts, such as intraductal papillary
mucinous neoplasms and mucinous cystic neoplasms, have the potential to progress
to pancreatic cancer. Considering the poor prognosis of pancreatic cancer, the
detection of a pancreatic cyst can be a source of anxiety for both the patient
and physician. This diagnosis in turn can lead to expensive, invasive, and even
harmful surveillance and treatment options. As a consequence, several national
and international guidelines for the management of pancreatic cysts have been
developed over the past decade. However, these guidelines rely on standard
clinical assessment, radiographical imaging, and ancillary fluid studies that
have insufficient sensitivity and specificity. The application of DNA-based
molecular techniques has emerged as an adjunct to the assessment of pancreatic
cysts. The cellular content of pancreatic cyst fluid aspirate is often suboptimal
for analysis, but DNA isolated from lysed or exfoliated cells within the cyst can
be analysed for genetic abnormalities. Moreover, whole exome sequencing and
targeted sequencing of the major pancreatic cysts has identified unique
mutational profiles for cyst type and genetic alterations that coincide with the
development of pancreatic cancer. In this Review, we discuss the major cystic
lesions of the pancreas and their underlying molecular pathology, current
management guidelines for pancreatic cysts, and integration of DNA-based
molecular testing within this field.
PMID- 28404021
TI - Effects of pre-emptive atropine on medetomidine induced bradycardia in dogs.
PMID- 28404022
TI - Comparison of propofol and etomidate for anesthetic induction in bulldogs.
PMID- 28404023
TI - Neuromuscular effects of cisatracurium in anesthetized dogs.
PMID- 28404024
TI - A comparison of the anesthetic effects of propofol, propofol-thiopental, diazepam
ketamine, and etomidate in greyhounds.
PMID- 28404025
TI - The effect of diazepam on isoflurane-fentanyl minimum alveolar concentration
(MAC) in the dog.
PMID- 28404026
TI - Comparative analgesic and cardiopulmonary effects of epidural bupivacaine and
ropivacaine in conscious dogs.
PMID- 28404027
TI - Effect of pre-operative administration of ketoprofen on platelet aggregation,
mucosal bleeding time and hematological indices in dogs after elective
ovariohysterectomy.
PMID- 28404028
TI - Comparison of epidural buprenorphine and morphine for post-operative analgesia in
dogs.
PMID- 28404029
TI - Effect of pre-operative administration of ketoprofen on post-operative pain in
dogs after elective ovariohysterectomy.
PMID- 28404030
TI - Pulmonary function, ventilator management and outcome of the ventilated canine
thoracic trauma patient with pulmonary contusions (1994-98).
PMID- 28404031
TI - The use of pulsed electromagnetic field (PEMF) therapy to provide post-operative
analgesia in the dog.
PMID- 28404032
TI - Evaluation of xylazine and ketamine for maintenance of anesthesia in horses.
PMID- 28404033
TI - Nitroprusside improves tumor perfusion during local 42 degrees C hyperthermia.
PMID- 28404034
TI - Repeated injectable anesthesia in six horses for cobalt therapy.
PMID- 28404035
TI - Cardiopulmonary measurements in six horses with naturally-acquired colic (acute
abdominal crisis).
PMID- 28404036
TI - Cardiovascular effects of desflurane in horses.
PMID- 28404037
TI - Cardiopulmonary function following anesthesia in horses experiencing hydro pool
recovery versus padded stall recovery.
PMID- 28404038
TI - Post-anesthetic ventilatory management in horses.
PMID- 28404039
TI - Analgesic, hemodynamic and respiratory effects of caudal epidurally administered
ropivacaine hydrochloride solution in mares.
PMID- 28404040
TI - Pharmacokinetics and toxicity of intravenously administered lithium chloride in
horses.
PMID- 28404041
TI - Identification of opioid receptors in equine synovial membranes.
PMID- 28404042
TI - Comparative evaluation of the analgesic effects of epidural morphine, alfentanil,
butorphanol, tramadol and U50488H in horses.
PMID- 28404043
TI - Hepatic effects of halothane or isoflurane anesthesia in goats.
PMID- 28404044
TI - Cardiovascular effects of desflurane in calves.
PMID- 28404045
TI - Cardiovascular effects of sevoflurane in Holstein calves.
PMID- 28404046
TI - Fecal corticosterone refects serum corticosterone in Florida Sandhill Cranes.
PMID- 28404047
TI - Cardiopulmonary effects of controlled ventilation in isoflurane-anesthetized
Hispaniolan Amazon Parrots.
PMID- 28404048
TI - Virtual Ventilator: a Win32 application to teach the principles of mechanical
ventilation.
PMID- 28404049
TI - Changes in the equine EEG during surgery: The effect of an intravenous infusion
of thiopentone.
PMID- 28404050
TI - French veterinary attitudes toward pain evaluation and control in dogs and cats.
PMID- 28404051
TI - Assessment of a medetomidine/propofol total intravenous anaesthesia (TIVA) for
clinical anaesthesia in equidae.
PMID- 28404052
TI - Caudal epidural injection of a combination of ketamine and xylazine for perineal
analgesia in horses.
PMID- 28404053
TI - Use of a laryngeal mask for airway maintenance during inhalation anaesthesia in
rabbits.
PMID- 28404054
TI - The effect of intramuscular dexmedetomidine and medetomidine on cardiorespiratory
variables during isoflurane anaesthesia in sheep.
PMID- 28404055
TI - Pre- versus post-operative administration of buprenorphine as part of a
reversible anaesthetic technique in rats.
PMID- 28404056
TI - Erratum.
PMID- 28404057
TI - Antinociceptive effects of intrathecal 5-HT agonists in sheep.
AB - OBJECTIVES: To examine the role of spinal 5-hydroxytryptamine (5-HT) binding
sites in nociceptive processing in conscious sheep and to study the role of 5-HT
agonists in mediating analgesia. STUDY DESIGN: Prospective controlled study.
ANIMALS: Nine adult healthy female sheep (Swaledale, Swaledale-cross or Clun
Forest) weighing 45-65 kg. METHODS: Intrathecal (IT) catheters were implanted at
the cervical (n = 5) or lumbar (n = 4) level of the spinal cord under general
anaesthesia. At least 1 week later, and at 1 week intervals thereafter, the
effects of intrathecal Ringer's solution (control), xylazine (100 MUg), 5-HT
creatinine sulphate (200, 400 and 800 MUg), RU24969 (200 MUg), alpha-Methyl-5-HT
and 1-(3-Chlorophenyl)-biguanide (CPBG) on the mechanical nociceptive threshold
(MT) were studied. Results were plotted as mean variable versus time curves.
Areas under portions of the curves (0-30 and 0-60 minutes) were measured and
expressed as mean +/- standard error. Differences between values for control and
drug trials were examined using the two-tailed Student's t-test. RESULTS:
Baseline values of MT were lower on the hind limbs than on the forelimbs.
Intrathecal Ringer's solution did not alter MT in the cervical or lumbar region.
Xylazine (100 MUg) produced a characteristic elevation in MT between 5 and 60 +
minutes. Lumbar IT injection of 5-HT (800 MUg) raised the MT more than cervical
injection, while cervical injection of RU24969 (200 MUg) raised the MT more than
lumbar administration. Cervical IT injection of alpha-Me-5-HT (500 MUg) produced
a marked and significant increase in MT while lumbar application had no effect.
CPBG (500 MUg) injection caused no significant effect on MT with either cervical
or lumbar applications. CONCLUSIONS: The activation of 5-HT1 and 5-HT2 receptors
particularly at the cervical level appears to be involved in spinal nociceptive
processing in the sheep. CLINICAL RELEVANCE: These effects, which lasted about 60
minutes, may have an implication in the development of new analgesic strategies
for animals.
PMID- 28404058
TI - Effects of thiopentone on the equine electroencephalogram during anaesthesia with
halothane in oxygen.
AB - OBJECTIVE: To characterise the effects of thiopentone on the equine
electroencephalogram during halothane anaesthesia. STUDY DESIGN: Prospective
controlled study. ANIMALS: Eight healthy Welsh mountain pony geldings between 5
and 9 years old and weighing between 270 and 330 kg (mean 301 kg). METHODS:
Anaesthesia was induced with thiopentone and maintained using halothane in
oxygen. End tidal halothane was maintained above 0.75 and below 0.85%. EEG was
recorded continuously and a binaural broad band click stimulus was provided
throughout the experiment at 6.1224 Hz. An infusion of 500 mg thiopentone was
given over 5 minutes. Samples were taken for blood gas analysis and plasma
thiopentone assay (HPLC) 5 minutes prior to the start of the infusion and at 3,
5, 7, 10, 15, 20, 30, 45 and 60 minutes. The median and 95th percentile of the
EEG were calculated using standard statistical techniques and the mid-latency of
the auditory evoked response was generated. The values of EEG variables at each
time point were compared to the average value for the 15 minute period before the
infusion was started. Arterial blood gas values and plasma thiopentone
concentration were compared to the baseline sample taken prior to the start of
the infusion. Comparisons were made using analysis of variance for repeated
measures followed by Dunnett's test if a significant difference was detected.
RESULTS: The peak serum plasma concentration was 14.5 +/- 2.4 MUg mL-1 (mean +/-
SD) occurring 5 minutes after the start of the infusion. The 95% spectral edge
frequency of the EEG decreased by a maximum of 27.4 +/- 18.4% 7 minutes after the
start of the thiopentone infusion. No changes were seen in median frequency of
the EEG or the second differential of the middle latency auditory evoked
response. CONCLUSIONS: These results, coupled with the lack of antinociceptive
action of thiopentone, support the hypothesis that median frequency of the EEG
may be a useful indicator of nociception in anaesthetized animals. CLINICAL
RELEVANCE: If the EEG is to become a useful monitoring technique then it is
important to understand the relative contribution of changing plasma
concentrations of the agents used in anaesthesia.
PMID- 28404059
TI - Evaluation of the analgesic properties of acepromazine maleate, oxymorphone,
medetomidine and a combination of acepromazine-oxymorphone.
AB - OBJECTIVE: To determine the presence and duration of analgesia after oxymorphone,
acepromazine maleate, acepromazine-oxymorphone combination and medetomidine
administration in dogs. STUDY DESIGN: Blinded, controlled study. ANIMALS: Six
adult beagle dogs. METHODS: Each dog participated in five trials receiving
acepromazine maleate (0.2 mg kg-1 IM), oxymorphone (0.2 mg kg-1 IM), acepromazine
oxymorphone drug combination (0.2 mg kg-1 each IM), medetomidine (20 MUg kg-1 IM)
and sterile saline (control). Two specially designed instruments were used for
analgesia determination: a heat device (HD) utilized a linear ramped intensity
incandescent bulb and a pressure device (PD) consisted of a pneumatic cylinder
that protruded a 2.5-cm bolt. The minimum pressure and heat necessary to produce
an avoidance response were determined. Analgesia testing was performed prior to
and at 30-minute intervals for six hours after drug administration. RESULTS:
Oxymorphone, acepromazine-oxymorphone and medetomidine significantly elevated
both pressure and heat response thresholds compared to controls and acepromazine.
Both medetomidine and acepromazine-oxymorphone provided a significantly longer
duration of analgesia than oxymorphone. No adverse effects were observed at any
of the thermal or pressure application sites. CONCLUSIONS: Oxymorphone,
medetomidine and acepromazine-oxymorphone produced significant analgesia with
medetomidine and acepromazine-oxymorphone providing the longest duration of
analgesia.
PMID- 28404060
TI - Sedative effects of hydromorphone or oxymorphone with or without acepromazine in
dogs.
PMID- 28404061
TI - Comparison of three premedication techniques on passage of an endoscope through
the pyloric sphincter in dogs.
PMID- 28404062
TI - Effect of medetomidine on inspiratory occlusion pressure in anesthetized dogs.
PMID- 28404063
TI - Effects of medetomidine premedication on cardiorespiratory responses and cortisol
levels in dogs undergoing ovariohysterectomy.
PMID- 28404064
TI - Influence of acetylpromazine or morphine on urine production in anesthetized
dogs.
PMID- 28404065
TI - Comparison of sedative and cardiorespiratory effects of medetomidine-butorphanol
and medetomidine-ketamine combination in dogs.
PMID- 28404066
TI - The effect of glycopyrrolate on the cardiopulmonary response to high and low dose
romifidine sedation in dogs.
PMID- 28404067
TI - Continuous wound infiltration versus epidural analgesia after hepato-pancreato
biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority
trial.
AB - BACKGROUND: Epidural analgesia is the international standard for pain treatment
in abdominal surgery. Although some studies have advocated continuous wound
infiltration with local anaesthetics, robust evidence is lacking, especially on
patient-reported outcome measures. We aimed to determine the effectiveness of
continuous wound infiltration in hepato-pancreato-biliary surgery. METHODS: In
this randomised controlled, open label, non-inferiority trial (POP-UP), we
enrolled adult patients undergoing hepato-pancreato-biliary surgery by subcostal
or midline laparotomy in two Dutch hospitals. Patients were centrally randomised
(1:1) to receive either pain treatment with continuous wound infiltration using
bupivacaine plus patient-controlled analgesia with morphine or to receive
(patient-controlled) epidural analgesia with bupivacaine and sufentanil. All
patients were treated within an enhanced recovery setting. Randomisation was
stratified by centre and type of incision. The primary outcome was the mean
Overall Benefit of Analgesic Score (OBAS) from day 1-5, a validated composite
endpoint of pain scores, opioid side-effects, and patient satisfaction (range 0
[best] to 28 [worst]). Analysis was per-protocol. The non-inferiority limit of
the mean difference was + 3.0. This trial is registered with the Netherlands
Trial Registry, number NTR4948. FINDINGS: Between Jan 20, 2015, and Sept 16,
2015, we randomly assigned 105 eligible patients: 53 to receive continuous wound
infiltration and 52 to receive epidural analgesia. One patient in the continuous
wound infiltration group discontinued treatment, as did five in the epidural
analgesia group; of these five patients, preoperative placement failed in three
(these patients were treated with continuous wound infiltration instead), one
patient refused an epidural, and data for the primary endpoint was lost for one.
Thus, 55 patients were included in the continuous wound infiltration group and 47
in the epidural analgesia group for the per-protocol analyses. Mean OBAS was 3.8
(SD 2.4) in the continuous wound infiltration group versus 4.4 (2.2) in the
epidural group (mean difference -0.62, 95% CI -1.54 to 0.30). Because the upper
bound of the one-sided 95% CI did not exceed +3.0, non-inferiority was shown.
Four (7%) patients in the continuous wound infiltration group and five (11%) of
those in the epidural group had an adverse event. One patient in the continuous
wound infiltration group had a serious adverse event (temporary hypotension and
arrhythmia after bolus injection); no serious adverse events were noted in the
epidural group. INTERPRETATION: These data suggest that continuous wound
infiltration is non-inferior to epidural analgesia in hepato-pancreato-biliary
surgery within an enhanced recovery setting. Further large-scale trials are
required to make a definitive assessment of non-inferiority. FUNDING: Academic
Medical Centre, Amsterdam, Netherlands.
PMID- 28404068
TI - Association between functional gastrointestinal disorders and migraine in
children and adolescents: a case-control study.
AB - BACKGROUND: Functional gastrointestinal disorders and migraine are both common
causes of medical attention. We have previously shown an association between
migraine and infant colic. In this case-control study, we aimed to establish
whether there is an association between migraine and other functional
gastrointestinal disorders in children and adolescents. METHODS: We included
children and adolescents aged 6-17 years presenting to the emergency department
of four tertiary hospitals in France and Italy. Patients diagnosed with either
migraine or tension-type headache by the hospital's paediatric neurologist were
enrolled as cases. Patients presenting to the emergency department with minor
trauma and no history of recurrent headache were enrolled as controls.
Investigators masked to a patient's group allocation diagnosed functional
gastrointestinal disorders using the Rome III diagnostic criteria. Univariable
and multivariable analyses were done to identify specific disorders and baseline
factors associated with migraines and tension-type headache. FINDINGS: Between
Nov 1, 2014, and Jan 31, 2015, we enrolled 648 controls and 424 cases (257
patients with migraine and 167 with tension-type headache). 83 (32%) children and
adolescents in the migraine group were diagnosed with functional gastrointestinal
disorders compared with 118 (18%) in the control group (p<0.0001). Multivariable
logistic regression showed a significant association between migraine and three
gastrointestinal disorders: functional dyspepsia (odds ratio 10.76, 95% CI 3.52
32.85; p<0.0001), irritable bowel syndrome (3.47, 1.81-6.62; p=0.0002), and
abdominal migraine (5.87, 1.95-17.69; p=0.002). By contrast, there was an inverse
association between migraine and functional constipation (0.34, 0.14-0.84,
p=0.02). 41 (25%) participants with tension-type headache had functional
gastrointestinal disorders, which did not significantly differ from the
prevalence of these disorders in the control group (p=0.07); no significant
association was noted between any functional gastrointestinal disease and tension
type headaches. INTERPRETATION: Three abdominal-pain-related functional
gastrointestinal disorders were associated with migraine in children and
adolescents. These findings are of value to the diagnosis and management of these
common diseases. Future studies should investigate whether antimigraine drugs are
of benefit in functional gastrointestinal disorders. FUNDING: None.
PMID- 28404070
TI - Pathophysiology of irritable bowel syndrome.
AB - Traditionally, irritable bowel syndrome has been considered to be a disorder with
no known underlying structural or biochemical explanation, but this concept is
likely to be outdated. In this Review we challenge the widely accepted view that
irritable bowel syndrome is an unexplained brain-gut disorder. There is
epidemiological evidence that, in a major subset of patients, gastrointestinal
symptoms arise first and only later do incident mood disorders occur.
Additionally, possible mechanisms for gut-brain dysfunction have been identified,
suggesting primary gut disturbances might be the underlying cause in a subgroup.
Underlying mechanisms that could lead to irritable bowel syndrome include genetic
factors (most notably an identified mutation of SCN5A); post-infectious changes,
chronic infections and disturbances in the intestinal microbiota; low-grade
mucosal inflammation, immune activation, and altered intestinal permeability;
disordered bile salt metabolism (in 10-20% of cases with diarrhoea);
abnormalities in serotonin metabolism; and alterations in brain function, which
could be primary or secondary factors. Identical irritable bowel syndrome
symptoms are probably due to different disease processes; grouping patients with
this disorder into either diarrhoea-predominant or constipation-predominant
subtypes promotes heterogeneity. An approach based on the underlying
pathophysiology could help to develop therapies that target causes and ultimately
provide a cure for patients with irritable bowel syndrome.
PMID- 28404069
TI - Patient-reported outcomes with sofosbuvir and velpatasvir with or without
ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory
analysis from the randomised, open-label ASTRAL-4 phase 3 trial.
AB - BACKGROUND: Hepatitis C virus (HCV) treatment regimens with direct-acting
antivirals have not been extensively studied in patients with decompensated
cirrhosis. We assessed patient-reported outcomes (PROs) in patients with
decompensated cirrhosis given a fixed-dose combination of sofosbuvir and
velpatasvir with and without ribavirin. METHODS: This study was an exploratory
analysis of data collected in a randomised, open-label phase 3 trial (ASTRAL-4)
in which patients with HCV-related decompensated cirrhosis were randomly assigned
to an all-oral fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100
mg) once daily for 12 weeks, sofosbuvir and velpatasvir plus oral ribavirin
(weight-based 1000 mg or 1200 mg) for 12 weeks, or sofosbuvir and velpatasvir for
24 weeks. Eligible patients were aged 18 years or older with any HCV genotype and
decompensated cirrhosis at screening. PROs were collected for the intention-to
treat population using four questionnaires, Short Form (36) Health Survey version
2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT
F), the Chronic Liver Disease Questionnaire-HCV Version (CLDQ-HCV), and the Work
Productivity Activity Index:HCV (WPAI), which were given prospectively to
patients before, during, and after treatment. The ASTRAL-4 study is registered
with ClinicalTrials.gov, number NCT02201901. FINDINGS: Patients were enrolled at
47 hepatology outpatient practices in the USA from Aug 19, 2014, to Dec 19, 2014.
267 patients with HCV-related decompensated cirrhosis were included. In patients
given sofosbuvir and velpatasvir for 12 weeks (n=90), clinically significant
improvements in PROs started 4 weeks after treatment initiation (+4.4 to +7.5
points on a 0-100 scale at treatment week 4). By the end of treatment, mean
improvements in PROs of +5.3 to +16.0 points were noted in all PROs except for
role emotional, mental component summary, and social wellbeing scores and work
productivity metrics by WPAI:HCV. Similar end-of-treatment improvements (+3.8 to
+17.0 points) were observed in patients given sofosbuvir and velpatasvir for 24
weeks (n=90). In patients given sofosbuvir and velpatasvir plus ribavirin (n=87),
PRO scores decreased within 4 weeks of treatment (-3.6 to -6.9 points), although
scores returned to the baseline levels by the end of treatment. After treatment
cessation, significant improvements in all PROs were similar between the
treatment groups (all p>0.01) and, by post-treatment week 24, improvements were
between +4.9 and +21.2 points. In multivariate analysis, predictors of PRO
impairment were treatment naivety, anxiety, use of anxiolytics, use of
antidepressants, use of opioids, ribavirin use, the presence of ascites,
encephalopathy, insomnia, and depression. INTERPRETATION: A clinically
significant early (within 4 weeks) and sustained improvement in PROs was observed
in patients with HCV-related decompensated cirrhosis who were given sofosbuvir
and velpatasvir without ribavirin. A similar regimen with ribavirin resulted in a
temporary decrease in PROs, which completely resolved after 8 weeks of treatment.
Accompanied by high efficacy, the favourable effect of treatment on PROs improves
patients' experience in this difficult-to-treat population with HCV. FUNDING:
Gilead Sciences.
PMID- 28404071
TI - Molecular endoscopy for targeted imaging in the digestive tract.
AB - Endoscopy uses optical imaging methods to investigate tissue in a non-destructive
manner with high resolution over a broad range of wavelengths, thus providing a
powerful tool to rapidly visualise mucosal surfaces in the digestive tract.
Molecular imaging is an important advancement that has been clinically
demonstrated for early cancer detection and guidance of therapy. With this
approach, imaging can be used to observe expression patterns of molecular targets
to improve understanding of key biological mechanisms that drive disease
progression. Prototype devices that collect fluorescence for wide-field or
microscopic images have been developed. Several targeting moieties, including
enzyme-activatable probes, antibodies, peptides, and lectins, have been
administered in preclinical and clinical imaging studies in vivo. These emerging
technologies provide useful approaches to study molecular events in different
signalling pathways, producing insights that could lead to improved interventions
to prevent and treat gastrointestinal diseases. In this Review, we introduce the
basic concepts that form the foundation for development of molecular endoscopy
and summarise key results from preclinical and clinical studies.
PMID- 28404072
TI - Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver
disease.
AB - Hepatocellular carcinoma is the fifth most common cancer and the second leading
cause of cancer-related death worldwide. Non-alcoholic fatty liver disease
(NAFLD) and non-alcoholic steatohepatitis have been identified as emergent risk
factors for this primary liver cancer. Incidence of NAFLD is increasing as a
consequence of the epidemic spread of metabolic syndrome, which can result in
progressive liver disease, leading to cirrhosis and its complications. Most data
about the prevalence and incidence of hepatocellular carcinoma in patients with
NAFLD are from a few population and cohort studies; its incidence is increasing
and it is likely to become a leading indication for liver transplantation,
especially in industrialised countries. In patients with NAFLD, hepatocellular
carcinoma can arise in the context of non-cirrhotic liver, suggesting a specific
carcinogenic pathway. Pathology studies have also described steatohepatitic
hepatocellular carcinoma as a specific histological variant. NAFLD is
underdiagnosed as causative liver disease, and patients are often diagnosed with
hepatocellular carcinoma in the advanced stage because of the absence of
efficient surveillance policies in this patient population. Management of
hepatocellular carcinoma in patients with NAFLD is also complicated by
comorbidities, mainly cardiac disease and diabetes, which negatively affect
eligibility for radical treatments, including hepatic resection and, especially,
liver transplantation. Finally, the effect of hepatocellular carcinoma treatments
on postoperative morbidity, mortality, and disease-free survival remains to be
precisely defined.
PMID- 28404074
TI - Gluten: going against the grain?
PMID- 28404073
TI - Optimum timing of treatment for hepatitis C infection relative to liver
transplantation.
AB - The approval of direct-acting antiviral agents that may be given orally in an
interferon-free regimen has greatly changed the landscape of treatment for
hepatitis C virus (HCV) infection, especially for patients with the most severe
disease, who have decompensated cirrhosis, or who are waiting for or have
undergone liver transplantation. Treatment with interferon proved to be
ineffective and poorly tolerated because of high risks of infection and
transplant rejection. The availability of new drugs poses new questions about the
optimum time to give treatment to prevent HCV recurrence, taking into account
efficacy, tolerance, and drug-drug interactions. Treatment is acceptable before
and after transplantation, but the two strategies have subtle differences. In
this Review, we present the available data on the treatment of HCV infection
before and after transplantation, and discuss new challenges for practice.
PMID- 28404075
TI - Hepatitis C: individualised medicine versus one pill fits all.
PMID- 28404076
TI - Perioperative analgesia in hepato-pancreato-biliary surgery.
PMID- 28404077
TI - A specific link between migraine and functional GI disorders.
PMID- 28404078
TI - Patient experience in HCV therapy: what really matters.
PMID- 28404083
TI - The challenge of antimicrobial resistance.
PMID- 28404084
TI - Tenofovir alafenamide for hepatitis B: evolution or revolution?
PMID- 28404085
TI - POLE mutations in colorectal cancer: a new biomarker?
PMID- 28404086
TI - Dynamic outcome prediction for paracetamol-related acute liver failure.
PMID- 28404091
TI - Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of
HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind,
phase 3, non-inferiority trial.
AB - BACKGROUND: Tenofovir alafenamide is a novel prodrug formulated to deliver the
active metabolite to target cells more efficiently than tenofovir disoproxil
fumarate at a lower dose, thereby reducing systemic exposure. In patients with
HIV, tenofovir alafenamide was as efficacious as tenofovir disoproxil fumarate,
with reduced bone and renal toxic effects. We compared the efficacy and safety of
the two drugs in patients with HBeAg-positive chronic hepatitis B virus (HBV)
infection in a non-inferiority study. METHODS: We did this ongoing double-blind,
non-inferiority study in 161 outpatient centres in 19 countries. Patients with
chronic HBV infection who were positive for the hepatitis B e antigen (HBeAg)
were randomly assigned (2:1) to receive either 25 mg tenofovir alafenamide or 300
mg tenofovir disoproxil fumarate with matching placebo. Randomisation was done by
a computer-generated allocation sequence (block size six) stratified by plasma
HBV DNA concentration and previous treatment experience. The primary efficacy
endpoint was the proportion of patients with HBV DNA less than 29 IU/mL at week
48 in all patients who were randomly assigned and received at least one dose of
study drug using a missing-equals-failed approach. The pre-specified non
inferiority margin was 10%. Key prespecified safety endpoints were bone and renal
parameters at week 48. This study is registered with ClinicalTrials.gov, number
NCT01940471. FINDINGS: Of the 1473 patients screened from Sept 11, 2013, to Dec
20, 2014, 875 eligible patients were randomly assigned and 873 received treatment
(581 with tenofovir alafenamide and 292 with tenofovir disoproxil fumarate). 371
(64%) patients receiving tenofovir alafenamide had HBV DNA less than 29 IU/mL at
week 48, which was non-inferior to the 195 (67%) of patients receiving tenofovir
disoproxil fumarate who had HBV DNA less than 29 IU/mL (adjusted difference -3.6%
[95% CI -9.8 to 2.6]; p=0.25). Patients given tenofovir alafenamide had a
significantly smaller decrease in bone mineral density at hip (mean change -0.10%
[95% CI -0.29 to 0.09] vs -1.72% [-2.02 to -1.41]; adjusted difference 1.62 [1.27
to 1.96]; p<0.0001) and at spine (mean change -0.42% [-0.66 to -0.17] vs -2.29% [
2.67 to -1.92]; adjusted difference 1.88 [1.44 to 2.31]; p<0.0001) as well as
smaller mean increases in serum creatinine at week 48 (0.01 mg/dL [0.00-0.02] vs
0.03 mg/dL [0.02-0.04]; p=0.02). The most common adverse events overall were
upper respiratory tract infection (51 [9%] of 581 patients receiving tenofovir
alafenamide vs 22 [8%] of 292 patients receiving tenofovir disoproxil fumarate),
nasopharyngitis (56 [10%] vs 16 [5%]), and headache (42 [7%] vs 22 [8%]). 22 (4%)
patients receiving tenofovir alafenamide and 12 (4%) patients receiving tenofovir
disoproxil fumarate experienced serious adverse events, none of which was deemed
by the investigator to be related to study treatment. 187 (32%) of 581 patients
in the tenofovir alafenamide group and 96 (33%) of 292 patients in the tenofovir
disoproxil fumarate group had grade 3 or 4 laboratory abnormalities, the most
common of which were elevations in ALT (62 [11%] of 577 patients receiving
tenofovir alafenamide and 36 [13%] of 288 patients receiving tenofovir disoproxil
fumarate) and AST (20 [3%] of 577 patients receiving tenofovir alafenamide and 19
[7%] of 288 patients receiving tenofovir disoproxil fumarate). INTERPRETATION: In
patients with HBeAg-positive HBV infection, tenofovir alafenamide was non
inferior to tenofovir disoproxil fumarate, and had improved bone and renal
effects. Longer term follow-up is needed to better understand the clinical impact
of these changes. FUNDING: Gilead Sciences.
PMID- 28404092
TI - Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of
patients with HBeAg-negative chronic hepatitis B virus infection: a randomised,
double-blind, phase 3, non-inferiority trial.
AB - BACKGROUND: The novel prodrug tenofovir alafenamide delivers the nucleotide
reverse transcriptase inhibitor tenofovir to target cells more efficiently at a
lower dose than tenofovir disoproxil fumarate, thereby reducing systemic
exposure. We compared the efficacy and safety of the two drugs in patients with
HBeAg-negative chronic hepatitis B virus (HBV) infection in a non-inferiority
study. METHODS: In this ongoing randomised, double-blind, phase 3, non
inferiority study in 105 centres in 17 countries, patients with HBeAg-negative
chronic HBV were randomly assigned (2:1) by a computer-generated allocation
sequence (block size six), stratified by plasma HBV DNA concentration and
previous treatment status, to receive once-daily oral doses of tenofovir
alafenamide 25 mg or tenofovir disoproxil fumarate 300 mg, each with matching
placebo. Participants, investigators, and those assessing outcomes were masked to
group assignment. Eligible patients were aged at least 18 years with HBeAg
negative chronic HBV infection (with plasma HBV DNA concentrations of >20 000
IU/mL), serum alanine aminotransferase concentrations of greater than 60 U/L in
men or greater than 38 U/L in women and at no more than ten times the upper limit
of normal, and estimated creatinine clearance of at least 50 mL/min (by the
Cockcroft-Gault method). The primary efficacy endpoint was the proportion of
patients who had HBV DNA less than 29 IU/mL at week 48 in those who received at
least one dose of study drug; the study was powered to show non-inferiority with
a 10% efficacy margin of tenofovir alafenamide compared with tenofovir disoproxil
fumarate. Bone and renal safety, and key secondary safety endpoints were assessed
sequentially. The study will be conducted for a total of 3 years as a double
blind comparison to assess the longer term response to treatment. This study is
registered with ClinicalTrials.gov, number NCT01940341. FINDINGS: Between Sept
12, 2013, and Oct 31, 2014, 426 patients were randomly assigned (285 assigned to
tenofovir alafenamide and 141 assigned to tenofovir disoproxil fumarate; one
patient assigned to tenofovir disoproxil fumarate did not receive the treatment.
268 (94%) of 285 patients receiving tenofovir alafenamide had HBV DNA less than
29 IU/mL at week 48 versus 130 (93%) of 140 patients receiving tenofovir
disoproxil fumarate (difference 1.8% [95% CI -3.6 to 7.2]; p=0.47), which
demonstrates non-inferiority. Patients receiving tenofovir alafenamide had
significantly smaller mean percentage declines in bone mineral density than those
receiving tenofovir disoproxil fumarate (hip -0.29% [95% CI -0.55 to -0.03] vs
2.16% [-2.53 to -1.79], adjusted percentage difference 1.87% [95% CI 1.42 to
2.32; p<0.0001]; spine -0.88% [-1.22 to -0.54] vs -2.51% [-3.09 to -1.94],
adjusted percentage difference 1.64% [95% CI 1.01 to 2.27]; p<0.0001). At week
48, mean change in serum creatinine was small in both groups (tenofovir
alafenamide 0.01 mg/dL [95% CI 0.00 to 0.02] vs tenofovir disoproxil fumarate
0.02 mg/dL [0.00 to 0.04], adjusted percentage difference -0.01 mg/dL [95% CI
0.03 to 0.01]; p=0.32), but patients receiving tenofovir alafenamide had a
smaller reduction in creatinine clearance (median change in estimated glomerular
filtration rate -1.8 mL/min [IQR -7.8 to 6.0] vs -4.8 mL/min [-12.0 to 3.0];
p=0.004). Most adverse events were mild to moderate in severity in the two
treatment groups. The most common adverse events overall were headache (tenofovir
alafenamide 40 [14%] patients vs tenofovir disoproxil fumarate 14 [10%]
patients), nasopharyngitis (30 [11%] vs 15 [11%]), and upper respiratory tract
infection (35 [12%] vs ten [7%]). 14 (5%) patients receiving tenofovir
alafenamide and nine (6%) patients receiving tenofovir disoproxil fumarate had
serious adverse events, none of which was deemed by investigators to be related
to study treatment; one patient in the tenofovir disoproxil fumarate group died,
but this was not deemed to be related to study treatment. INTERPRETATION: In
patients with HBeAg-negative chronic HBV, the efficacy of tenofovir alafenamide
was non-inferior to that of tenofovir disoproxil fumarate, and had improved bone
and renal effects. Longer term follow-up is needed to better understand the
clinical impact of these changes. FUNDING: Gilead Sciences.
PMID- 28404093
TI - Somatic POLE proofreading domain mutation, immune response, and prognosis in
colorectal cancer: a retrospective, pooled biomarker study.
AB - BACKGROUND: Precision cancer medicine depends on defining distinct tumour
subgroups using biomarkers that may occur at very modest frequencies. One such
subgroup comprises patients with exceptionally mutated (ultramutated) cancers
caused by mutations that impair DNA polymerase epsilon (POLE) proofreading.
METHODS: We examined the association of POLE proofreading domain mutation with
clinicopathological variables and immune response in colorectal cancers from
clinical trials (VICTOR, QUASAR2, and PETACC-3) and colorectal cancer cohorts
(Leiden University Medical Centre 1 and 2, Oslo 1 and 2, Bern, AMC-AJCC-II, and
Epicolon-1). We subsequently investigated its association with prognosis in stage
II/III colorectal cancer by Cox regression of pooled individual patient data from
more than 4500 cases from these studies. FINDINGS: Pathogenic somatic POLE
mutations were detected in 66 (1.0%) of 6517 colorectal cancers, and were
mutually exclusive with mismatch repair deficiency (MMR-D) in the 6277 cases for
whom both markers were determined (none of 66 vs 833 [13.4%] of 6211; p<0.0001).
Compared with cases with wild-type POLE, cases with POLE mutations were younger
at diagnosis (median 54.5 years vs 67.2 years; p<0.0001), were more frequently
male (50 [75.8%] of 66 vs 3577 [55.5%] of 6445; p=0.0010), more frequently had
right-sided tumour location (44 [68.8%] of 64 vs 2463 [39.8%] of 6193; p<0.0001),
and were diagnosed at an earlier disease stage (p=0.006, chi2 test for trend).
Compared with mismatch repair proficient (MMR-P) POLE wild-type tumours, POLE
mutant colorectal cancers displayed increased CD8+ lymphocyte infiltration and
expression of cytotoxic T-cell markers and effector cytokines, similar in extent
to that observed in immunogenic MMR-D cancers. Both POLE mutation and MMR-D were
associated with significantly reduced risk of recurrence compared with MMR-P
colorectal cancers in multivariable analysis (HR 0.34 [95% CI 0.11-0.76];
p=0.0060 and 0.72 [0.60-0.87]; p=0.00035), although the difference between the
groups was not significant. INTERPRETATION: POLE proofreading domain mutations
identify a subset of immunogenic colorectal cancers with excellent prognosis.
This association underscores the importance of rare biomarkers in precision
cancer medicine, but also raises important questions about how to identify and
implement them in practice. FUNDING: Cancer Research UK, Academy of Medical
Sciences, Health Foundation, EU, ERC, NIHR, Wellcome Trust, Dutch Cancer Society,
Dutch Digestive Foundation.
PMID- 28404094
TI - Development and validation of a dynamic outcome prediction model for paracetamol
induced acute liver failure: a cohort study.
AB - BACKGROUND: Early, accurate prediction of survival is central to management of
patients with paracetamol-induced acute liver failure to identify those needing
emergency liver transplantation. Current prognostic tools are confounded by
recent improvements in outcome independent of emergency liver transplantation,
and constrained by static binary outcome prediction. We aimed to develop a simple
prognostic tool to reflect current outcomes and generate a dynamic updated
estimation of risk of death. METHODS: Patients with paracetamol-induced acute
liver failure managed at intensive care units in the UK (London, Birmingham, and
Edinburgh) and Denmark (Copenhagen) were studied. We developed prognostic models,
excluding patients who underwent transplantation, using Cox proportional hazards
in a derivation dataset, and tested in initial and recent external validation
datasets. Mortality was estimated in patients who had emergency liver
transplantation. Model discrimination was assessed using area under receiver
operating characteristic curve (AUROC) and calibration by root mean square error
(RMSE). Admission (day 1) variables of age, Glasgow coma scale, arterial pH and
lactate, creatinine, international normalised ratio (INR), and cardiovascular
failure were used to derive an initial predictive model, with a second (day 2)
model including additional changes in INR and lactate. FINDINGS: We developed and
validated new high-performance statistical models to support decision making in
patients with paracetamol-induced acute liver failure. Applied to the derivation
dataset (n=350), the AUROC for 30-day survival was 0.92 (95% CI 0.88-0.96) using
the day 1 model and 0.93 (0.88-0.97) using the day 2 model. In the initial
validation dataset (n=150), the AUROC for 30-day survival was 0.89 (0.84-0.95)
using the day 1 model and 0.90 (0.85-0.95) using the day 2 model. Assessment of
calibration using RMSE in prediction of 30-day survival gave values of 0.1642 for
the day 1 model and 0.0626 for the day 2 model. In the external validation
dataset (n=412), the AUROC for 30-day survival was 0.91 (0.87-0.94) using the day
1 model and 0.91 (0.88-0.95) using the day 2 model, and assessment of calibration
using RMSE gave values of 0.079 for the day 1 model and 0.107 for the day 2
model. Applied to patients who underwent emergency liver transplantation (n=116),
median predicted 30-day survival was 51% (95% CI 33-85). INTERPRETATION: The
models developed here show very good discrimination and calibration, confirmed in
independent datasets, and suggest that many patients undergoing transplantation
based on existing criteria might have survived with medical management alone. The
role and indications for emergency liver transplantation in paracetamol-induced
acute liver failure require re-evaluation. FUNDING: Foundation for Liver
Research.
PMID- 28404096
TI - The mesentery: structure, function, and role in disease.
AB - Systematic study of the mesentery is now possible because of clarification of its
structure. Although this area of science is in an early phase, important advances
have already been made and opportunities uncovered. For example, distinctive
anatomical and functional features have been revealed that justify designation of
the mesentery as an organ. Accordingly, the mesentery should be subjected to the
same investigatory focus that is applied to other organs and systems. In this
Review, we summarise the findings of scientific investigations of the mesentery
so far and explore its role in human disease. We aim to provide a platform from
which to direct future scientific investigation of the human mesentery in health
and disease.
PMID- 28404097
TI - Hepatitis B and hepatitis C in southeast and southern Asia: challenges for
governments.
AB - In 2015, the Coalition to Eradicate Viral Hepatitis in Asia Pacific gathered
leading hepatitis experts from Bangladesh, India, Indonesia, Malaysia, Pakistan,
the Philippines, and Thailand to discuss common challenges to the burden posed by
hepatitis B virus (HBV) and hepatitis C virus (HCV), to learn from each other's
experience, and identify sustainable approaches. In this report, we summarise
these discussions. Countries differ in their policy responses to HBV and HCV;
however, substantial systemic, cultural, and financial barriers to achievement of
elimination of these infections persist in all countries. Common challenges to
elimination include limited availability of reliable epidemiological data;
insufficient public awareness of risk factors and modes of transmission, leading
to underdiagnosis; high rates of transmission through infected blood products,
including in medical settings; limited access to care for people who inject
drugs; prevailing stigma and discrimination against people infected with viral
hepatitis; and financial barriers to treatment and care. Despite these
challenges, promising examples of effective programmes, public-private
initiatives, and other innovative approaches are evident in all countries we
studied in Asia Pacific. The draft WHO Global Health Sector Strategy on Viral
Hepatitis 2016-21 provides a solid framework upon which governments can build
their local strategies towards viral hepatitis. However, greater recognition by
national governments and the international community of the urgency to
comprehensively tackle both HBV and HCV are still needed. In all countries,
strategic plans and policy goals need to be translated into resources and
concrete actions, with national governments at the helm, to enable a sustainable
response to the rising burden of hepatitis B and C in all countries.
PMID- 28404095
TI - Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and
pancreatic cancer.
AB - Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia.
Type 2 diabetes, the most prevalent form, is characterised initially by impaired
insulin sensitivity and subsequently by an inadequate compensatory insulin
response. Diabetes can also develop as a direct consequence of other diseases,
including diseases of the exocrine pancreas. Historically, diabetes due to
diseases of the exocrine pancreas was described as pancreatogenic or
pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c
diabetes. It is important to note that type 3c diabetes is not a single entity;
it occurs because of a variety of exocrine pancreatic diseases with varying
mechanisms of hyperglycaemia. The most commonly identified causes of type 3c
diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma,
haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this
Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type
3c diabetes secondary to chronic pancreatitis and pancreatic ductal
adenocarcinoma, and highlight several important knowledge gaps.
PMID- 28404099
TI - Correction.
PMID- 28404098
TI - Screening for liver fibrosis in the general population: a call for action.
AB - Liver cirrhosis is one of the main causes of death and disability-adjusted life
years worldwide. Generally, cirrhosis develops after a long period of liver-cell
injury that leads to the deposition of collagen, leading to progressive fibrosis
and nodule formation in the liver tissue. Most patients are diagnosed in late
stages when liver decompensation or liver cancer develops. The diagnosis is
rarely made in early stages-when liver fibrosis is mild to moderate but cirrhosis
is not yet established-because the disease is asymptomatic. No strategies for
detection of liver fibrosis at these early stages have been developed, but
therapies are more effective in early stages than late stages of chronic liver
diseases, so enabling early detection is an important research topic. Non
invasive methods for assessing liver fibrosis have been developed, of which the
most commonly used are transient elastography-which estimates liver fibrosis by
measuring liver stiffness-and serum biomarkers of fibrosis. Studies have shown
that 6-7% of the adult population without known liver disease have liver
fibrosis, mostly associated with non-alcoholic fatty liver disease. These data
suggest that programmes of screening for liver fibrosis in the general population
should be assessed.
PMID- 28404100
TI - Correction.
PMID- 28404101
TI - The Lancet Gastroenterology & Hepatology: putting the inside out.
PMID- 28404107
TI - Infliximab or ciclosporin for acute severe ulcerative colitis?
PMID- 28404108
TI - Ombitasvir, paritaprevir, and ritonavir plus ribavirin in adults with hepatitis C
virus genotype 4 infection and cirrhosis (AGATE-I): a multicentre, phase 3,
randomised open-label trial.
AB - BACKGROUND: Hepatitis C virus (HCV) genotype 4 infection is most commonly
reported in sub-Saharan Africa and the Middle East; however, prevalence is
increasing worldwide through immigration. HCV genotype 4 accounts for 20% of all
infections, but clinical trial data for treatment remain limited. We assessed the
combination of two direct-acting antivirals, ombitasvir (NS5A inhibitor) and
paritaprevir (NS3/4A protease inhibitor; co-dosed with ritonavir) plus ribavirin
in patients with HCV genotype 4 infection and compensated cirrhosis. METHODS: In
this multicentre, randomised, open-label phase 3 trial (AGATE-I), treatment-naive
and interferon or pegylated interferon and ribavirin treatment-experienced
patients with HCV genotype 4 infection and compensated cirrhosis were recruited
from academic, public, and private hospitals in Austria, Belgium, Canada, France,
Germany, Greece, Italy, and the USA. Key eligibility criteria were age 18 years
or older, with chronic HCV infection assessed by the presence of anti-HCV
antibodies or HCV RNA. Patients were randomly assigned (1:1) to receive 25 mg
ombitasvir, 150 mg paritaprevir, and 100 mg ritonavir once daily, with weight
based ribavirin dosed twice daily for either 12 weeks or 16 weeks. Randomisation
was stratified by HCV treatment history (treatment-experienced vs treatment-naive
patients) and further stratified by type of non-response to previous HCV
treatment (null responders, partial responders, or relapsers) for treatment
experienced patients. Treatments were assigned by an interactive response
technology system with computer-generated randomisation lists prepared by
personnel from the study's funding sponsor who were not involved with the conduct
of the study or with data analysis. The primary outcome was the proportion of
patients with a sustained virological response (HCV RNA <25 IU/mL) at post
treatment week 12 (SVR12) in the intention-to-treat population, with the lower
97.5% CI compared with a clinically relevant threshold (67%; based on SVR
reported for pegylated interferon and ribavirin) to achieve superiority. The
safety population included all patients who received at least one dose of study
drug, and safety analyses were done by the treatment duration received (12 weeks
or 16 weeks). Data presented are from the planned primary interim analysis of
part one of the study when all patients enrolled in part one had reached post
treatment week 12 or prematurely discontinued from the study. This trial is
registered with ClinicalTrials.gov, number NCT02265237, and part two of the trial
is ongoing but closed to new participants. FINDINGS: Between Nov 18, 2014, and
May 19, 2015, we enrolled 120 eligible patients, with 59 patients assigned to
receive 12 weeks of treatment and 61 patients assigned to receive 16 weeks of
treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin. One
patient in the 12-week group experienced virological breakthrough and one
discontinued prematurely after the first day of treatment. One patient missed the
post-treatment week 12 visit in the 16-week group. SVR12 was achieved in 57 (97%;
97.5% CI 86.7-99.2) of 59 patients in the 12-week group and 60 (98%; 89.6-99.8)
of 61 in the 16-week group. Adverse events in more than 10% of all patients were
asthenia (11 [18%] of 60 in the 12-week group; 19 [32%] of 60 in the 16-week
group), fatigue (ten [17%] in the 12-week group; 20 [33%] in the 16-week group),
headache (14 [23%] in the 12-week group; 14 [23%] in the 16-week group), anaemia
(nine [15%] in the 12-week group; 12 [20%] in the 16-week group), pruritus (five
[8%] in the 12-week group; 14 [23%] in the 16-week group), nausea (six [10%] in
the 12-week group; eight [13%] in the 16-week group), and dizziness (four [7%] in
the 12-week group; nine [15%] in the 16-week group). INTERPRETATION: With SVR12
achieved in a high proportion of patients, no post-treatment relapses, and a
similar adverse event profile for the 12-week and 16-week treatment groups,
extending treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin
beyond 12 weeks seems to have no additional benefit for patients with HCV
genotype 4 infection and compensated cirrhosis and might not be necessary for
this patient group. FUNDING: AbbVie.
PMID- 28404109
TI - Genotype 4 and the global challenge of hepatitis C treatment.
PMID- 28404110
TI - Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C
virus genotype 4 infection in Egyptian patients with or without compensated
cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial.
AB - BACKGROUND: In Egypt, chronic hepatitis C virus (HCV) infection occurs in around
10% of the population (about 8 million individuals), and is a leading cause of
liver cirrhosis, hepatocellular carcinoma, and mortality. Although HCV genotype 4
constitutes about 20% of HCV infections worldwide, the prevalence in Egypt is
more than 90%. We assessed the efficacy and safety of the two direct-acting
antiviral drugs ombitasvir, an NS5A inhibitor, and paritaprevir, an NS3/4A
protease inhibitor dosed with ritonavir, plus ribavirin in treatment of chronic
HCV infection in Egypt. METHODS: AGATE-II was a phase 3, open-label, partly
randomised trial in patients with chronic HCV genotype 4 infection recruited from
five academic and hepatology centres in Egypt. Patients were HCV treatment-naive
or treatment-experienced with interferon-based regimens. Eligible patients were
aged 18 years or older, and had been chronically infected with HCV genotype 4 for
at least 6 months with a plasma HCV RNA concentration of more than 1000 IU/mL at
screening. Patients without cirrhosis were assigned to receive 12 weeks of 25 mg
ombitasvir, 150 mg paritaprevir, and 100 mg ritonavir orally once daily plus
weight-based ribavirin. Patients with compensated cirrhosis were randomly
assigned (1:1) to receive the same treatment for either 12 weeks or 24 weeks.
Randomisation was stratified by previous pegylated interferon and ribavirin
treatment experience using a web-based interactive response technology system and
computer-generated schedules prepared by personnel from the funder's statistics
department. Investigators were masked to randomisation schedules and were
informed of each patient's assigned treatment by the interactive response
technology system immediately after allocation. The primary endpoint was the
proportion of patients with a sustained virological response (HCV RNA <15 IU/mL)
12 weeks after the last dose of study drug (SVR12). All patients who received at
least one dose of study drugs were included in the primary and safety analysis.
This study is registered with ClinicalTrials.gov, number NCT02247401. FINDINGS:
Between Nov 4, 2014, and March 16, 2015, we screened 182 patients with HCV
infection, of whom 160 were eligible for inclusion; 100 patients were assessed as
not having cirrhosis and were given 12 weeks of treatment, and 60 patients
assessed as having cirrhosis were randomly assigned to the 12-week treatment
group (n=31) or the 24-week treatment group (n=29). 94 (94%; 95% CI 88-97) of 100
patients in the without cirrhosis group, 30 (97%; 84-99) of 31 patients in the
cirrhosis 12-week treatment group, and 27 (93%; 78-98) of 29 patients in the
cirrhosis 24-week treatment group achieved SVR12. The most common adverse events
in patients without cirrhosis were headache (41 [41%]) and fatigue (35 [35%]).
Fatigue occurred in nine (29%) patients in the cirrhosis 12-week treatment group
and 11 (38%) patients in the cirrhosis 24-week treatment group, and headache
occurred in nine (29%) patients in the cirrhosis 12-week treatment group and in
10 (35%) patients in the cirrhosis 24-week treatment group. Adverse events were
predominantly mild or moderate in severity, and laboratory abnormalities were not
clinically meaningful. No patients discontinued treatment because of an adverse
event. One serious adverse event in the group without cirrhosis was attributed to
study drugs by the investigators; the patient had deep venous thrombosis.
INTERPRETATION: Ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12
weeks achieved SVR12 in a high proportion of patients and was well tolerated in
Egyptian patients with HCV genotype 4 infection with or without compensated
cirrhosis. Extension of treatment to 24 weeks in patients with cirrhosis did not
improve the proportion of patients achieving SVR12. A shorter duration regimen
could be useful to address the significant burden of HCV genotype 4 infection in
patients with compensated cirrhosis. FUNDING: AbbVie.
PMID- 28404111
TI - Global incidence and mortality of pancreatic diseases: a systematic review, meta
analysis, and meta-regression of population-based cohort studies.
AB - BACKGROUND: There is a lack of robust estimates of the worldwide incidence and
mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and
pancreatic cancer in the general population. Our aim was to quantitate and
compare the incidence and mortality of major pancreatic diseases in high-quality
population-based cohort studies. METHODS: Three databases (PubMed, Embase, and
Scopus) were searched independently by two reviewers. Data from eligible studies
were subject to meta-analysis to obtain global estimates. A number of
prespecified subgroup analyses and meta-regression analyses were also done.
FINDINGS: 48 population-based cohort studies (35 on pancreatic cancer, ten on
acute pancreatitis, three on chronic pancreatitis, and none on pancreatic cysts)
were identified, with a total study population of 296 million individuals and 119
000 patients with pancreatic diseases. Global estimates of incidence and
mortality were 8.14 cases (95% CI 6.63-9.98) per 100 000 person-years and 6.92
deaths (95% CI 3.72-12.89) per 100 000 person-years for pancreatic cancer, 33.74
cases (95% CI 23.33-48.81) per 100 000 person-years and 1.60 deaths (95% CI 0.85
1.58) per 100 000 person-years for acute pancreatitis, and 9.62 cases (95% CI
7.86-11.78) per 100 000 person-years and 0.09 deaths (95% CI 0.02-0.47) per 100
000 person-years for chronic pancreatitis. Subgroup analysis based on the WHO
regions showed that the incidences of both pancreatic cancer and acute
pancreatitis, and mortality from pancreatic cancer, were significantly higher in
the American region than in the European and Western Pacific regions, while the
incidence of chronic pancreatitis was significantly higher in the European region
than in the American region. Mortality from pancreatic cancer was lowest in the
Southeast Asian region. The incidence of chronic pancreatitis was twice as high
in men as in women, although there was no difference between sexes for pancreatic
cancer or acute pancreatitis. INTERPRETATION: Globally, acute pancreatitis is the
most common pancreatic disease whilst pancreatic cancer is the most lethal.
However, their burden is not equal across the globe. The epidemiological
estimates reported in this study could inform future high-quality studies.
FUNDING: None.
PMID- 28404112
TI - Assessing the burden of gastrointestinal disease: room for improvement?
PMID- 28404113
TI - Pathogenesis and novel treatment options for non-alcoholic steatohepatitis.
AB - Non-alcoholic fatty liver disease affects 20-40% of the population. Its active
form, non-alcoholic steatohepatitis (NASH), is characterised by hepatocyte
injury, liver inflammation, and progression of fibrosis, and has emerged as one
of the most important causes of liver failure and hepatocellular carcinoma.
Weight reduction of 10% by dietary restriction and regular exercise is sufficient
to reverse NASH in most patients, but in practice this reduction is often not
achieved. Available drugs such as vitamin E, pioglitazone, and pentoxifylline
have borderline efficacy, but are limited by potential side-effects and
toxicities, and do not improve liver fibrosis. However, basic and translational
research has improved our understanding of the pathophysiology of NASH, thereby
identifying several promising new treatment targets. Several drugs are in phase 2
and 3 development and could enter clinical practice in the near future. In this
Review, we discuss the pathogenesis, treatment evaluation, existing therapies,
and potential new treatments for NASH.
PMID- 28404114
TI - Functional gastrointestinal disorders: what's new for Rome IV?
PMID- 28404115
TI - Advances in primary sclerosing cholangitis.
AB - Primary sclerosing cholangitis is a chronic, progressive cholangiopathy that
frequently affects men and is associated with inflammatory bowel disease.
Although the cause of the disease is still debated, a genetic association and
link to immune-mediated disease triggered by environmental factors are thought to
contribute. The disease can present as isolated imaging abnormalities,
biochemical changes, cholangiocarcinoma, or end-stage complications such as
cirrhosis. Symptoms of primary sclerosing cholangitis include fatigue, jaundice,
pruritus, or steatorrhoea. Differentiation of primary sclerosing cholangitis can
be challenging because other chronic cholangiopathies can present similarly;
however, the distinction is necessary to optimise disease surveillance.
Management involves assessment for comorbid inflammatory bowel disease and
exclusion of other associated cholangiopathic disorders. Patients with primary
sclerosing cholangitis have a poor prognosis; progression to liver cirrhosis is
common, and an increased risk of hepatobiliary and colorectal cancers is present
in those with inflammatory bowel disease. Although much research involves
locating an active therapy that can alter the disease course, the only available
treatment is liver transplantation, and risk for disease recurrence remains. Use
of ursodeoxycholic acid can improve alkaline phosphatase and bilirubin
concentrations but does not alter the disease course. In this Review, we
summarise aetiological theories, provide an update on hepatobiliary malignancies
that require surveillance, and discuss exciting areas of investigation for
potential treatment.
PMID- 28404116
TI - Evidence of reducing ethanol content in beverages to reduce harmful use of
alcohol.
AB - Alcohol use is a major contributor to the burden of gastrointestinal disease.
WHO's global strategy to reduce harmful use of alcohol encourages the alcohol
industry to contribute to this effort. However, evidence that alcohol producers
have contributed to the reduction of harmful use of alcohol is scarce. Reduction
of alcoholic strength of beer has been proposed and initiated as one potential
way forward. We examine the evidence base for the success of such an initiative.
Direct evidence from natural experiments or other controlled studies is scarce.
We identified three potential mechanisms for how reduction of alcoholic strength
could affect harmful use of alcohol: by current drinkers replacing standard
alcoholic beverages with similar beverages of lower alcoholic strength, without
increasing the quantity of liquid consumed; by current drinkers switching to no
alcohol alternatives for part of the time, thereby reducing their average amount
of ethanol consumed; and by initiating alcohol use in current abstainers. The
first mechanism seems to be the most promising to potentially reduce harm, but
much will depend on actual implementation, and only an independent assessment
will be able to identify effects on harmful drinking. The potential of alcoholic
strength reduction is independent of initiation by law or by self-initiative of
the industry.
PMID- 28404117
TI - End-stage liver disease in eastern Europe and central Asia: action is needed.
PMID- 28404118
TI - Acute oesophageal necrosis.
PMID- 28404119
TI - Correction.
PMID- 28404120
TI - PPIs: adding (airway) insult to (kidney) injury?
PMID- 28404121
TI - Chronic hepatitis C: less of a problem than first thought?
PMID- 28404122
TI - Peginterferon add-on: an added benefit?
PMID- 28404123
TI - Understanding and management of anxiety and mood disorders in inflammatory bowel
disease.
PMID- 28404124
TI - Hepatitis C virus reinfection-more to come?
PMID- 28404125
TI - Antimicrobial resistance in liver disease: better diagnostics are needed.
PMID- 28404126
TI - Hepatitis E: urgent action needed.
PMID- 28404127
TI - Direct-acting antiviral therapy for hepatitis E virus?
PMID- 28404133
TI - Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to
nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in
patients with HBe antigen-negative chronic hepatitis B and sustained undetectable
plasma hepatitis B virus DNA: a randomised, controlled, open-label trial.
AB - BACKGROUND: Findings from uncontrolled studies suggest that addition of pegylated
interferon in patients with HBe antigen (HBeAg)-negative chronic hepatitis B
receiving nucleos(t)ide analogues with undetectable plasma hepatitis B virus
(HBV) DNA might increase HBs antigen (HBsAg) clearance. We aimed to assess this
strategy. METHODS: In this randomised, controlled, open-label trial, we enrolled
patients aged 18-75 years with HBeAg-negative chronic hepatitis B and documented
negative HBV DNA while on stable nucleos(t)ide analogue regimens for at least 1
year from 30 hepatology tertiary care wards in France. Patients had to have an
alanine aminotransferase concentration of less than or equal to five times the
upper normal range, no hepatocellular carcinoma, and a serum alpha fetoprotein
concentration of less than 50 ng/mL, normal dilated fundus oculi examination, and
a negative pregnancy test in women. Patients with contraindications to pegylated
interferon were not eligible. A centralised randomisation used computer-generated
lists of random permuted blocks of four with stratification by HBsAg titres (< or
>=2.25 log10 IU/mL) to allocate patients (1:1) to receive a 48 week course of
subcutaneous injections of 180 MUg per week of pegylated interferon alfa-2a in
addition to the nucleos(t)ide analogue regimen or to continue to receive
nucleos(t)ide analogues only. The primary endpoint was HBsAg loss at week 96 by
intention-to-treat analysis. This trial is closed and registered with
ClinicalTrials.gov, number NCT01172392. FINDINGS: Between Jan 20, 2011, and July
18, 2012, we randomly allocated 185 patients (92 [50%] to pegylated interferon
and nucleos(t)ide analogues and 93 [50%] to nucleos(t)ide analogues alone). We
excluded two patients from the pegylated interferon plus nucleos(t)ide analogues
group from analyses because of withdrawal of consent (one patient) or violation
of inclusion criteria (one patient). At week 96, loss of HBsAg was reported in
seven (7.8%) of 90 patients in the pegylated interferon plus nucleos(t)ide
analogues group versus three (3.2%) of 93 in the nucleos(t)ide analogues-alone
group (difference 4.6% [95% CI -2.6 to 12.5]; p=0.15). 85 (94%) of 90 patients
started pegylated interferon, three (4%) of whom had a dose reduction and 17
(20%) had an early discontinuation of pegylated interferon (seven [41%] for
serious adverse events). Grade 3 and 4 adverse events were more frequent in the
pegylated interferon plus nucleos(t)ide analogues group (26 [29%] grade 3 adverse
events; 19 [21%] grade 4 adverse events) than in the nucleos(t)ide analogues
alone group (three [3%] grade 3; six [6%] grade 4). INTERPRETATION: Addition of a
48 week course of pegylated interferon to nucleos(t)ide analogue therapy in
patients with HBeAg-negative chronic hepatitis B with undetectable HBV DNA for a
least 1 year was poorly tolerated and did not result in a significant increase of
HBsAg clearance. FUNDING: Institut national de la sante et de la recherche
medicale-Agence nationale de recherches sur le sida et les hepatites virales
(France Recherche Nord&sud Sida-vih Hepatites).
PMID- 28404134
TI - Effect of psychological therapy on disease activity, psychological comorbidity,
and quality of life in inflammatory bowel disease: a systematic review and meta
analysis.
AB - BACKGROUND: Inflammatory bowel disease is associated with psychological
comorbidity and impaired quality of life. Psychological comorbidity could affect
the natural history of inflammatory bowel disease. Psychological therapies might
therefore have beneficial effects on disease activity, mood, and quality of life
in patients with inflammatory bowel disease. We did a systematic review and meta
analysis examining these issues. METHODS: In this systematic review and meta
analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the
Cochrane Central Register of Controlled Trials for articles published between
1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients
with inflammatory bowel disease aged at least 16 years that compared
psychological therapy with a control intervention or usual treatment were
eligible. We pooled dichotomous data to obtain relative risks of induction of
remission in active disease or prevention of relapse of quiescent disease, with
95% CIs. We pooled continuous data to estimate standardised mean differences in
disease activity indices, anxiety, depression, perceived stress, and quality-of
life scores in patients dichotomised into those with clinically active or
quiescent disease, with 95% CIs. We extracted data from published reports and
contacted the original investigators of studies for which the required data were
not available. We pooled all data using a random-effects model. FINDINGS: The
search identified 1824 studies, with 14 RCTs of 1196 patients eligible for
inclusion. The relative risk of relapse of quiescent inflammatory bowel disease
with psychological therapy versus control was 0.98 (95% CI 0.77-1.24; p=0.87;
I2=50%; six trials; 518 patients). We observed a significant difference in
depression scores (standardised mean difference -0.17 [-0.33 to -0.01]; p=0.04;
I2=0%; seven trials; 605 patients) and quality of life (0.30 [0.07-0.52]; p=0.01;
I2=42%; nine trials; 578 patients) with psychological therapy versus control at
the end of therapy for patients with quiescent disease. However, these beneficial
effects were lost at final point of follow-up (depression scores -0.11 [-0.27 to
0.05], p=0.17, I2=0%, eight trials, 593 patients; quality of life 0.15 [-0.05 to
0.34], p=0.14, I2=22%, ten trials, 577 patients). When we assessed the effect of
individual physiological therapies on quality of life, only cognitive behavioural
therapy had any significant beneficial effect (0.37 [0.02-0.72]). We noted no
effect on disease activity indices or other psychological wellbeing scores when
compared with control in patients with quiescent disease. Dichotomous data for
induction of remission and continuous data for change in clinical disease
activity indices, depression, anxiety, and perceived stress scores were only
reported in one RCT of patients with active disease. Quality of life was assessed
in two RCTs of patients with active disease, but was not significantly different
between intervention and control groups (0.27 [-0.05 to 0.59]). INTERPRETATION:
Psychological therapies, and cognitive behavioural therapy in particular, might
have small short-term beneficial effects on depression scores and quality of life
in patients with inflammatory bowel disease. Further RCTs of these interventions
in patients with coexistent psychological distress are required. FUNDING: None.
PMID- 28404136
TI - Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in patients
with HIV.
AB - Liver disease is a leading cause of morbidity and mortality among people with
HIV, and in this era of safer and more effective hepatitis C therapy, non
alcoholic fatty liver disease (NAFLD) could soon emerge as the most common liver
disease in this population. NAFLD is common among patients with HIV, and might be
more likely to progress to non-alcoholic steatohepatitis (NASH) and NAFLD-related
fibrosis or cirrhosis in these patients than in individuals without HIV. Several
mechanisms of NAFLD pathogenesis are postulated to explain the disease severity
in patients with HIV; these mechanisms include the influence of the gut
microbiome, and also metabolic, genetic, and immunological factors. Although
treatment strategies are currently based on modification of NAFLD risk factors,
many new drugs are now in clinical trials, including trials specifically in
patients with HIV. Thus, the identification and risk-stratification of patients
with HIV and NAFLD are becoming increasingly important for accurately counselling
of these patients regarding their prognosis and for establishing the most
appropriate disease-altering therapy.
PMID- 28404135
TI - Incidence, risk factors, and prevention of hepatitis C reinfection: a population
based cohort study.
AB - BACKGROUND: People remain at risk of reinfection with hepatitis C virus (HCV),
even after clearance of the primary infection. We identified factors associated
with HCV reinfection risk in a large population-based cohort study in British
Columbia, Canada, and examined the association of opioid substitution therapy and
mental health counselling with reinfection. METHODS: We obtained data from the
British Columbia Hepatitis Testers Cohort, which includes all individuals tested
for HCV or HIV at the British Columbia Centre for Disease Control Public Health
Laboratory during 1990-2013 (when data were available). We defined cases of HCV
reinfection as individuals with a positive HCV PCR test after either spontaneous
clearance (two consecutive negative HCV PCR tests spaced >=28 days apart without
treatment) or a sustained virological response (SVR; two consecutive negative HCV
PCR tests spaced >=28 days apart 12 weeks after completing interferon-based
treatment). We calculated incidence rates of HCV reinfection (per 100 person
years of follow-up) and corresponding 95% CIs assuming a Poisson distribution,
and used a multivariable Cox proportional hazards model to examine reinfection
risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type,
HIV co-infection, number of mental health counselling visits, levels of material
and social deprivation, and alcohol and injection drug use), and the association
of opioid substitution therapy and mental health counselling with HCV reinfection
among people who inject drugs (PWID). FINDINGS: 5915 individuals with HCV were
included in this study after clearance (3690 after spontaneous clearance and 2225
after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous
clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a
median of 5.4 years (IQR 2.9-8.7), and the median time to reinfection was 3.0
years (1.5-5.4). The overall incidence rate of reinfection was 1.27 (95% CI 1.15
1.39) per 100 person-years of follow-up over a total of 35 672 person-years, with
significantly higher rates in the spontaneous clearance group (1.59, 1.44-1.76)
than in the SVR group (0.48, 0.36-0.63). With the adjusted Cox proportional
hazards model, we noted higher reinfection risks in the spontaneous clearance
group (adjusted hazard ratio [HR] 2.71, 95% CI 2.00-3.68), individuals co
infected with HIV (2.25, 1.78-2.85), and PWID (1.53, 1.21-1.92) than with other
reinfection risk factors. Among the 1604 PWID with a current history of injection
drug use, opioid substitution therapy was significantly associated with a lower
risk of reinfection (adjusted HR 0.73, 95% CI 0.54-0.98), as was engagement with
mental health counselling services (0.71, 0.54-0.92). INTERPRETATION: The
incidence of HCV reinfection was higher among HIV co-infected individuals, those
who spontaneously cleared HCV infection, and PWID. HCV treatment complemented
with opioid substitution therapy and mental health counselling could reduce HCV
reinfection risk among PWID. These findings support policies of post-clearance
follow-up of PWID, and provision of harm-reduction services to minimise HCV
reinfection and transmission. FUNDING: The British Columbia Centre for Disease
Control and the Canadian Institutes of Health Research.
PMID- 28404132
TI - Global prevalence and genotype distribution of hepatitis C virus infection in
2015: a modelling study.
AB - BACKGROUND: The 69th World Health Assembly approved the Global Health Sector
Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become
a reality with the recent launch of direct acting antiviral therapies. Reliable
disease burden estimates are required for national strategies. This analysis
estimates the global prevalence of viraemic HCV at the end of 2015, an update of
and expansion on-the 2014 analysis, which reported 80 million (95% CI 64-103)
viraemic infections in 2013. METHODS: We developed country-level disease burden
models following a systematic review of HCV prevalence (number of studies,
n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process
was used to gain country expert consensus and validate inputs. Published
estimates alone were used for countries where expert panel meetings could not be
scheduled. Global prevalence was estimated using regional averages for countries
without data. FINDINGS: Models were built for 100 countries, 59 of which were
approved by country experts, with the remaining 41 estimated using published data
alone. The remaining countries had insufficient data to create a model. The
global prevalence of viraemic HCV is estimated to be 1.0% (95% uncertainty
interval 0.8-1.1) in 2015, corresponding to 71.1 million (62.5-79.4) viraemic
infections. Genotypes 1 and 3 were the most common cause of infections (44% and
25%, respectively). INTERPRETATION: The global estimate of viraemic infections is
lower than previous estimates, largely due to more recent (lower) prevalence
estimates in Africa. Additionally, increased mortality due to liver-related
causes and an ageing population may have contributed to a reduction in
infections. FUNDING: John C Martin Foundation.
PMID- 28404137
TI - Genetics of inflammatory bowel disease: beyond NOD2.
AB - The study of the genetic underpinnings of inflammatory bowel disease has made
great progress since the identification of NOD2 as a major susceptibility gene.
Novel genotyping and sequencing technologies have led to the discovery of 242
common susceptibility loci, 45 of which have been fine-mapped to statistically
conclusive causal variants; 50 genes associated with very-early-onset
inflammatory disease have been identified. The evolving genetic architecture of
inflammatory bowel disease has deepened our understanding of its pathogenesis
through identification of major disease associated pathways-knowledge that has
the potential to indicate novel drug targets or markers for personalised
medicine. However, many causal variants have yet to be identified, and a large
proportion of missing heritability still needs to be accounted for. In addition,
the medical and scientific communities are probably not yet fully harnessing the
power of these genetic discoveries.
PMID- 28404138
TI - Correction to Lancet Gastroenterol Hepatol 2017; 2: 200-10.
PMID- 28404139
TI - Increasing organ donation rates: is legislation enough?
PMID- 28404140
TI - Acute appendicitis with a mass: the evidence is here.
PMID- 28404141
TI - Colon cancer surgery: is it what you do, or the way you do it that matters?
PMID- 28404142
TI - Colon cancer in Asian patients with ulcerative colitis.
PMID- 28404143
TI - Salvage chemotherapy for advanced gastric cancer: more than a false hope?
PMID- 28404144
TI - The fibrosis benefit index for assessment of therapeutic benefit in non-alcoholic
steatohepatitis.
PMID- 28404145
TI - The role of the mesentery in Crohn's disease.
PMID- 28404146
TI - Refining the anatomy of the mesentery: how can it affect management of colorectal
cancer?
PMID- 28404147
TI - The role of the mesentery in Crohn's disease.
PMID- 28404148
TI - Screening studies of transient elastography and FibroTest in the general
population.
PMID- 28404149
TI - Screening studies of transient elastography and FibroTest in the general
population - Authors' reply.
PMID- 28404150
TI - The effect of trainee research collaboratives in the UK.
PMID- 28404154
TI - Active observation versus interval appendicectomy after successful non-operative
treatment of an appendix mass in children (CHINA study): an open-label,
randomised controlled trial.
AB - BACKGROUND: Despite a scarcity of supporting evidence, most surgeons recommend
routine interval appendicectomy after successful non-operative treatment of an
appendix mass in children. We aimed to compare routine interval appendicectomy
with active observation. METHODS: We enrolled participants in the CHildren's
INterval Appendicectomy (CHINA) study, a multicentre, open-label, randomised
controlled study at 19 specialist paediatric surgery centres, 17 of which were in
the UK, one in Sweden, and one in New Zealand. 106 children aged 3-15 years were
assigned (1:1) by weighted minimisation to interval appendicectomy or active
observation with minimisation for age, trial centre, sex, and presence of a
faecolith on imaging. Eligible children had acute appendicitis with an appendix
mass and were successfully treated without appendicectomy or other surgical
intervention. Children were excluded from the study if they had coexisting
gastrointestinal disease or had a substantial coexisting medical condition or
immune defect. Because of the nature of the interventions, blinding was not
possible. The primary outcome was the proportion of children developing
histologically proven recurrent acute appendicitis or a clinical diagnosis of
recurrent appendix mass within 1 year of enrolment after successful non-operative
treatment of appendix mass (active observation group) and incidence of severe
complications related to interval appendicectomy. Data were analysed on an
intention-to-treat basis. This study is registered with ISRCTN, number 93815412.
FINDINGS: Between Aug 8, 2011, and Dec 31, 2014, we randomly assigned 106
patients, 52 patients to interval appendicectomy and 54 to active observation.
Two children in the interval appendicectomy group were withdrawn due to
withdrawal of consent; two in the active observation group were withdrawn because
they became ineligible after allocation. Six children under active observation
had histologically proven recurrent acute appendicitis. Three children in the
interval appendicectomy group had severe complications. Thus, the proportion of
children with histologically proven recurrent acute appendicitis under active
observation was 12% (95% CI 5-23) and the proportion of children with severe
complications related to interval appendicectomy was 6% (95% CI 1-17).
INTERPRETATION: More than three-quarters of children could avoid appendicectomy
during early follow-up after successful non-operative treatment of an appendix
mass. Although the risk of complications after interval appendicectomy is low,
complications can be severe. Adoption of a wait-and-see approach, reserving
appendicectomy for those who develop recurrence or recurrent symptoms, results in
fewer days in hospital, fewer days away from normal daily activity, and is
cheaper than routine interval appendicectomy. These high-quality data will allow
clinicians, parents, and children to make an evidence-based decision regarding
the justification for interval appendicectomy. FUNDING: BUPA Foundation.
PMID- 28404155
TI - Survival outcomes following laparoscopic versus open D3 dissection for stage II
or III colon cancer (JCOG0404): a phase 3, randomised controlled trial.
AB - BACKGROUND: Although benefits of laparoscopic surgery compared with open surgery
have been suggested, the long-term survival of patients undergoing laparoscopic
surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did
a randomised controlled trial to establish non-inferiority of laparoscopic
surgery to open surgery. METHODS: We did an open-label, multi-institutional,
randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20-75
years who had histologically proven colon cancer; tumours located in the caecum
or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without
involvement of other organs, node stages N0-2, and metastasis stage M0; and
tumour size of 8 cm or smaller were included. Only accredited surgeons did
surgery as an operator or instructor. Patients were randomly assigned (1:1)
preoperatively to undergo D3 resection either by an open route or a laparoscopic
route, via phone call or fax to the Japan Clinical Oncology Group (JCOG) Data
Center. Randomisation used a minimisation method with a biased-coin assignment
according to tumour location (caecum, ascending vs sigmoid, rectosigmoid) and
institution. The primary endpoint was overall survival and was analysed by
intention to treat. The non-inferiority margin for the hazard ratio (HR) was set
at 1.366. This study is registered with UMIN Clinical Trials Registry, number
C000000105, and ClinicalTrials.gov, number NCT00147134. FINDINGS: Between Oct 1,
2004, and March 27, 2009, 1057 patients were randomly assigned to either open
surgery (n=528) or laparoscopic surgery (n=529). 5-year overall survival was
90.4% (95% CI 87.5-92.6) for open surgery and 91.8% (89.1-93.8) for laparoscopic
surgery. Laparoscopic D3 surgery was not non-inferior to open surgery for overall
survival (HR 1.06, 90% CI 0.79-1.41; pnon-inferiority=0.073). 65 (13%) patients
in the open surgery group and 53 (10%) patients in the laparoscopic surgery group
had grade 2-4 adverse events. Grade 2-4 adverse events included diarrhoea (15
[3%] in the open surgery group vs 14 [3%] in the laparoscopic surgery group),
paralytic ileus (six [1%] vs nine [2%]), and small intestine bowel obstruction
(16 [3%] vs 11 [2%]). Two treatment-related deaths occurred in the open surgery
group: one patient died 7 days after surgery (probably due to myocardial
infarction), and one patient died from febrile neutropenia, pneumonia, diarrhoea,
and gastrointestinal haemorrhage during postoperative chemotherapy.
INTERPRETATION: Laparoscopic D3 surgery was not non-inferior to open D3 surgery
in terms of overall survival for patients with stage II or III colon cancer.
However, because overall survival in both groups was similar and better than
expected, laparoscopic D3 surgery could be an acceptable treatment option for
patients with stage II or III colon cancer. FUNDING: National Cancer Center
Research and Development Fund, Grant-in-Aid for Cancer Research, and Health and
Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of
Health, Labour and Welfare of Japan.
PMID- 28404156
TI - Risk of colorectal cancer in Asian patients with ulcerative colitis: a systematic
review and meta-analysis.
AB - BACKGROUND: The increased risk of colorectal cancer in ulcerative colitis is well
known. The risk of sporadic colorectal cancer in Asian populations is considered
low and risk estimates of colorectal cancer related to ulcerative colitis from
Asia vary. This meta-analysis is an Asian perspective on the risk of colorectal
cancer related to ulcerative colitis. METHODS: We searched PubMed and Embase for
terms related to colorectal cancer in ulcerative colitis from inception to July
1, 2016. The search for published articles was done by country for all countries
in Asia. We included studies with information on the prevalence and cumulative
risk of colorectal cancer at various timepoints. A random-effects meta-analysis
was done to calculate the pooled prevalence as well as a cumulative risk at 10
years, 20 years, and 30 years of disease. FINDINGS: Our search identified 2575
articles; of which 44 were eligible for inclusion. Our analysis included a total
of 31 287 patients with ulcerative colitis with a total of 293 reported
colorectal cancers. Using pooled prevalence estimates from various studies, the
overall prevalence was 0.85% (95% CI 0.65-1.04). The risks for colorectal cancer
were 0.02% (95% CI 0.00-0.04) at 10 years, 4.81% (3.26-6.36) at 20 years, and
13.91% (7.09-20.72) at 30 years. Subgroup analysis by stratifying the studies
according to region or period of the study did not reveal any significant
differences. INTERPRETATION: We found the risk of colorectal cancer in Asian
patients with ulcerative colitis was similar to recent estimates in Europe and
North America. Adherence to screening is therefore necessary. Larger population
based, prospective studies are required for better estimates of the risk.
FUNDING: Indo-US Science and Technology Forum.
PMID- 28404157
TI - Nab-paclitaxel versus solvent-based paclitaxel in patients with previously
treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non
inferiority, phase 3 trial.
AB - BACKGROUND: Weekly administration of solvent-based paclitaxel is one of the
standard second-line chemotherapy regimens for advanced gastric cancer.
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) was developed to improve
the solubility of paclitaxel and does not need premedication to avoid infusion
related reactions associated with solvent-based paclitaxel. Additionally, higher
doses of nab-paclitaxel can be administered over a shorter infusion time and at
higher drug concentrations compared with solvent-based paclitaxel. We aimed to
investigate the efficacy and safety of nab-paclitaxel versus solvent-based
paclitaxel in patients with previously treated advanced gastric cancer. METHODS:
We did a randomised, open-label, non-inferiority, phase 3 trial at 72
institutions in Japan. Patients aged 20 years or older with advanced gastric
adenocarcinoma refractory to a fluoropyrimidine-containing first-line
chemotherapy regimen, with progressive disease or a relapse fewer than 24 weeks
after the final dose of adjuvant chemotherapy were randomly assigned (1:1:1) to
receive intravenous nab-paclitaxel (260 mg/m2) every 3 weeks (on day 1 of a 21
day cycle), weekly nab-paclitaxel (100 mg/m2, on days 1, 8, and 15 of a 28-day
cycle), or weekly solvent-based paclitaxel (80 mg/m2, on days 1, 8, and 15 of a
28-day cycle). Randomisation was done with the minimisation method, with
stratification for previous use of docetaxel, presence of peritoneal metastases,
and Eastern Cooperative Oncology Group (ECOG) performance status. The primary
endpoint was overall survival in the full analysis set, which included all
randomly assigned patients who received at least one dose of study drug, with a
non-inferiority margin of 1.25 for the hazard ratio. This trial is registered
with Japan Pharmaceutical Information Center Clinical Trial, number JapicCTI
132059, and has been completed. FINDINGS: Between March 13, 2013, and May 14,
2015, 741 patients were randomly assigned to nab-paclitaxel every 3 weeks
(n=247), weekly nab-paclitaxel (n=246), or weekly solvent-based paclitaxel
(n=248). Median follow-up for overall survival was 9.99 months (IQR 6.05-15.05).
Median overall survival was 10.3 months (95% CI 8.7-11.4) in the group that
received in the nab-paclitaxel every 3 weeks, 11.1 months (9.9-13.0) in the
weekly nab-paclitaxel group, and 10.9 months (9.4-11.8) in the weekly solvent
based paclitaxel group. Weekly nab-paclitaxel was non-inferior to weekly solvent
based paclitaxel (hazard ratio 0.97, 97.5% CI 0.76-1.23; non-inferiority one
sided p=0.0085), whereas nab-paclitaxel every 3 weeks was not non-inferior to
solvent-based paclitaxel (1.06, 95% CI 0.87-1.31; non-inferiority one-sided
p=0.062). The main grade 3 or worse adverse drug reactions were neutropenia (158
[65%] of 244 patients in the group that received nab-paclitaxel every 3 weeks vs
99 [41%] of 241 patients in the weekly nab-paclitaxel group vs 71 [29%] of 243
patients in the weekly solvent-based paclitaxel group), peripheral sensory
neuropathy (49 [20%] vs six [2%] vs six [2%]), and febrile neutropenia (30 [12%]
vs seven [3%] vs two [1%]). Hypersensitivity reactions were less frequent with
nab-paclitaxel every 3 weeks (two [1%] patients) and weekly nab-paclitaxel (three
[1%] patients) than with weekly solvent-based paclitaxel (13 [5%] patients). Four
treatment-related deaths were reported overall (pneumonia in one patient in the
group that received nab-paclitaxel every 3 weeks, febrile neutropenia/pneumonia
in one patient, and septic shock in one patient in the weekly nab-paclitaxel
group, and respiratory disease/interstitial lung disease in one patient in the
weekly solvent-based paclitaxel group). INTERPRETATION: As the trial showed that
weekly nab-paclitaxel was non-inferior to weekly solvent-based paclitaxel in
terms of overall survival, the advantages of the nab-paclitaxel formulation make
it a potential regimen for second-line treatment of gastric cancer. FUNDING:
Taiho Pharmaceutical.
PMID- 28404160
TI - Editorial.
PMID- 28404158
TI - Prevalence of clinically significant liver disease within the general population,
as defined by non-invasive markers of liver fibrosis: a systematic review.
AB - As of 2016, there is no evidence-based pathway to stratify the risk of chronic
liver disease in a general population setting. Non-invasive tests of liver
fibrosis might provide a mechanism for earlier diagnosis. These tests have been
extensively validated in the hospital setting but their performance in a general
population setting is unclear. We did a systematic review of non-invasive tests
used to stratify patients at risk of clinically significant liver disease in a
general population setting and report the prevalence of chronic liver disease as
defined by these tests. We systematically searched Embase, MEDLINE, Web of
Science, reference lists from the original studies identified, and recent
conference proceedings. All study designs were considered. 19 studies were
identified, in which 11 non-invasive tests were used. Only transient elastography
and FibroTest were compared with histological endpoints. The prevalence of liver
fibrosis varied between 0.7% and 25.7%. More focused stratification for advanced
liver fibrosis (0.9-2.0%) or cirrhosis (0.1-1.7%) narrowed the estimates of
prevalence. Investigators from studies targeting patients with risk factors of
liver disease, such as non-alcoholic fatty liver disease, hazardous alcohol use,
or type 2 diabetes, reported higher prevalence of advanced liver fibrosis (0
27.9%) and cirrhosis (2.4-4.0%) than those in the general population. Validated
non-invasive tests for liver fibrosis consistently detected otherwise
unrecognised liver disease in the general population. Reliance on abnormal liver
function tests will miss most patients with significant liver injury. New
pathways to stratify chronic liver disease, with the use of non-invasive markers
of liver fibrosis, are needed in the general population setting.
PMID- 28404159
TI - A microbiota-centric view of diseases of the upper gastrointestinal tract.
AB - The distinctive anatomy and physiology of the upper gastrointestinal tract and
the difficulty of obtaining samples led to the theory that it was bacteria free.
However, multiomics studies are indicating otherwise. Although influenced by both
oral and gastric bacteria, the resident microbial ecosystem in the oesophagus is
dominated by Streptococcus. A shift from Gram-positive to Gram-negative bacteria
occurs in oesophagitis and Barrett's oesophagus, and this shift might be involved
in the pathogenesis of oesophageal adenocarcinoma. The gastric microenvironment
is populated by microbial communities mainly of the Firmicutes, Actinobacteria,
Bacteroidetes, and Proteobacteria phyla and species of the Lactobacillus,
Streptococcus, and Propionibacterium genera. The composition of gastric
microbiota is highly dynamic, and is influenced by acid suppression, gastric
inflammation, and Helicobacter pylori. Duodenal microbes are also implicated in
the onset and outcome of coeliac disease. Bacteria of the genera Bacteroides,
Clostridium, and Staphylococcus dominate the duodenal flora in active coeliac
disease whereas lactobacilli and bifidobacteria decrease. Although knowledge of
the composition of the microbiota of the upper gastrointestinal tract has
advanced substantially, this information is far from being translated to the
clinical setting. In this Review, we assess the data related to the potential
contribution of microbes to the susceptibility for and pathogenesis of upper
gastrointestinal diseases.
PMID- 28404162
TI - Anaesthesia in the fourth dimension. Is biological scaling relevant to veterinary
anaesthesia?
PMID- 28404161
TI - Comparative analgesic and cardiopulmonary effects of bupivacaine and ropivacaine
in the epidural space of the conscious dog.
AB - OBJECTIVE: To compare the cardiopulmonary effects and sensory blockade of
epidural bupivacaine and ropivacaine. STUDY DESIGN: Prospective randomized study.
ANIMALS: Six young adult medium-sized crossbred dogs weighing 25.7 +/- 7.1 kg.
METHOD: Dogs were chronically implanted with a lumbosacral epidural catheter.
Acepromazine sedated dogs received all treatments: 0.5% bupivacaine at 0.14 mL kg
1 (LB5) or 0.22 mL kg-1 (HB5); 0.5% ropivacaine at 0.14 mL kg-1 (LR5) or 0.22 mL
kg-1 (HR5); 0.75% bupivacaine at 0.22 mL kg-1 (HB7.5) or 0.75% ropivacaine at
0.22 mL kg-1 (HR7.5). Loss of sensation was tested at the level of the perineum,
hind toe webs, flank, and caudodorsal rib areas before injection, and post
injection (PI) up to 150 minutes PI. Systemic arterial blood pressure and heart
rate were recorded before injection, and every 10 minutes PI until 150 minutes
PI. Arterial blood gas analyses were performed prior to injection, and at 30, 60
and 150 minutes PI. RESULTS: No statistical differences existed between groups
for the cardiopulmonary data or time to onset of block. Group HR7.5 had lower
systolic (10-70 minutes PI) and diastolic (10-70 minutes PI) blood pressures and
group HR5 had lower mean (10-90 minutes PI) and diastolic (10-90 minutes PI)
blood pressures compared to baseline. Heart rate was lower compared to baseline
in groups LR5 and HB7.5. A significant, but mild metabolic acidosis developed in
groups LR5 and HB7.5 (150 minutes PI). No differences were present for the
duration of block between groups, but duration of block in the dorsocaudal rib
area was shorter in group HR5 compared to HR7.5. CONCLUSION: Epidural ropivacaine
and bupivacaine at the doses used have mild effects on the cardiopulmonary
system, and extent of block are similar. CLINICAL RELEVANCE: The 0.75%
concentration of bupivacaine and ropivacaine at 0.22 mL kg-1 appeared to
contribute to greater success of block (>80%) at dermatomes L5-L7.
PMID- 28404163
TI - Anaesthetic potency of isoflurane in cattle: determination of the minimum
alveolar concentration.
AB - OBJECTIVE: To determine the minimum alveolar concentration (MAC) of isoflurane in
cattle. STUDY DESIGN: Prospective study. ANIMALS: Sixteen healthy adult female
Holstein-Friesian cattle weighing 612 +/- 17 kg (* +/- SEM) and aged 5.7 +/- 0.9
years old. METHODS: The unsedated cattle were restrained in right lateral
recumbency using a rope harness technique. Anaesthesia was induced with
isoflurane (ISO) in oxygen via a face mask connected to a large-animal,
semiclosed anaesthetic circle system. Each cow was intubated with a cuffed
orotracheal tube (25 mm ID). Inspired and end-tidal ISO were monitored using a
calibrated infra red analyser with a methane filter. The MAC of ISO that
prevented gross purposeful movement in response to a tail and dewclaw clamp was
determined. The time from the start of ISO administration to intubation, the time
interval between discontinuance of ISO and the time the animal regained sternal
recumbency, were recorded. Time to standing and quality of recovery were also
recorded. RESULTS: The time from the start of ISO administration to tracheal
intubation was 18.68 +/- 2.77 minutes. The MAC of ISO in these cattle was 1.27 +/
0.03% (1.14 +/- 0.01% corrected to sea level). Time to sternal recumbency after
90 +/- 16 minutes of anaesthesia from intubation was 4.60 +/- 0.58 minutes and
time to standing was 6.70 +/- 1.02 minutes. All cattle were extubated when they
regained sternal recumbency. CONCLUSION: The MAC of isoflurane in these cattle
was 1.27 +/- 0.03% (1.14 +/- 0.01% corrected to sea level). ISO provided a smooth
induction to, and rapid recovery from, anaesthesia. CLINICAL RELEVANCE: Knowledge
of the MAC of ISO in cattle will facilitate its appropriate clinical use.
PMID- 28404164
TI - beta-endorphin immunoreactivity during anaesthesia in equidae.
AB - OBJECTIVE: To determine the effects of surgery, hypoxia, hypercapnia and flunixin
administration on plasma beta-endorphin immunoreactivity (BEI) in anaesthetized
horses. STUDY DESIGN: Prospective crossover study. ANIMALS: Six healthy adult
Welsh Mountain ponies and seven healthy adult Thoroughbreds. METHODS: Ponies were
anaesthetized with thiopentone and halothane or with pentobarbitone and the
horses with guaiphenesin, thiopentone and halothane. Ponies were anaesthetized
for 2 hours and on separate occasions underwent a period of hypoxia, hypercapnia,
anaesthesia only, or were given flunixin at induction. The horses were
anaesthetized for 2 hours and on separate occasions underwent surgery to relocate
one carotid artery subcutaneously or anaesthesia only. Plasma samples were taken
pre-anaesthesia, at 20 minute intervals during, and after anaesthesia for BEI
assay using radio-immunoassay. Analysis of variance of the concentration-time
curve was used for statistical analysis. RESULTS: Pre-anaesthetic beta-endorphin
immunoreactivity (BEI) values ranged between 5.7 and 20.4 pmol L-1. Induction of
anaesthesia caused a five to 10 fold increase in mean plasma BEI in all cases
except the hypercapnia group. Halothane anaesthesia increased BEI in ponies and
horses but there were no significant changes during pentobarbitone anaesthesia.
The increase in BEI in the hypoxic group was greater (peak value 136.8 +/- 32.2
pmol L-1) and sustained for a longer period compared with levels in those given
halothane alone or in those which became hypercapnic. There was marked individual
variation in the flunixin group and changes were not significant. Surgery in the
horses resulted in the highest peak values in the study (182.5 +/- 153.0 pmol L
1) but the AUC was not significantly higher than in the same animals without
surgery, where the peak value was 102.9 +/- 42.1 pmol L-1. CONCLUSIONS: Beta
endorphin appeared to be a sensitive marker of an endocrine stress response but
its physiological role during equine anaesthesia is unknown. CLINICAL RELEVANCE:
Unknown.
PMID- 28404165
TI - Effects of a medetomidine-midazolam-butorphanol combination on renal cortical,
intestinal and muscle microvascular blood flow in isoflurane anaesthetized dogs:
a laser Doppler study.
AB - OBJECTIVE: To obtain renal cortical, ileal, colonic and skeletal muscle
microvascular blood flow measurements in dogs using the laser Doppler technique
and to characterize the effects of medetomidine-midazolam-butorphanol combination
on these flows. STUDY DESIGN: Prospective randomized experimental study. ANIMALS:
Fourteen clinically normal beagles (two groups of seven), aged 1-4 years and
weighing 13.2 +/- 1.8 kg. METHODS: All dogs were anaesthetized with 1.7% end
tidal isoflurane in oxygen. In the treatment group, after instrumentation and
when anaesthesia was considered stable, medetomidine (1 mg m-2 body surface area
(BSA)) was administered intramuscularly (time 0). Midazolam (1 mg kg-1) and
butorphanol (0.1 mg kg-1) were administered intravenously 20 minutes later.
Atipamezole (2.5 mg m-2 BSA) was administered intramuscularly 60 minutes after
medetomidine. In the control group, saline (0.5, 2.5 and 0.25 mL) was
administered at the corresponding times. Heart rate, systolic, diastolic and mean
arterial pressures, body temperature, renal cortical, ileal, colonic and skeletal
muscle microvascular blood flows were measured before time 0, and 5, 15, 25, 40,
60, 65, 70 and 90 minutes thereafter. RESULTS: Heart rate, ileal and skeletal
muscle blood flows decreased in the treatment group, while no changes were
observed in the control group. CONCLUSIONS: Laser Doppler flowmetry allowed the
measurement of microvascular blood flow in different organs. The medetomidine
midazolam-butorphanol combination decreases intestinal and skeletal muscle
microvascular blood flows, while renal cortical blood flow is maintained.
CLINICAL RELEVANCE: Medetomidine-midazolam-butorphanol combination can be used to
induce a short duration anaesthesia in dogs, but it will induce cardiovascular
depression. This depression appears to be accompanied by a redistribution of
blood flow.
PMID- 28404166
TI - The effect of pre-anaesthetic medication on the incidence of cardiac arrhythmias
during halothane anaesthesia in cats.
AB - OBJECTIVE: To compare the incidence of arrhythmias in cats receiving either
acepromazine or diazepam for pre-anaesthetic medication prior to halothane
anaesthesia. STUDY DESIGN: A blinded, randomized clinical study. ANIMALS: Forty
six healthy cats undergoing surgery. METHODS: Animals were allocated to one of
two groups for pre-anaesthetic medication. Group 1 received diazepam (0.2 mg kg
1). Group 2 received acepromazine (0.02 mg kg-1). The trial drug was administered
intramuscularly in combination with buprenorphine (0.01 mg kg-1) 30 minutes prior
to induction of anaesthesia with propofol (approximately 5 mg kg-1). Anaesthesia
was maintained using halothane: delivered concentration was 1-2% carried in
oxygen and nitrous oxide via an endotracheal tube attached to an Ayre's T-piece
(with Jackson-Rees modification) breathing system. The incidence of cardiac
arrhythmias was determined by continuously monitoring the electrocardiogram from
the time of induction until recovery occurred. Demographical group
characteristics were compared using analysis of variance. The incidence of
cardiac arrhythmias was compared by the Chi squared test. Statistical
significance was set at the 5% level. RESULTS: The two groups were similar in
weight, age, length and type of procedure undertaken. The incidence of
arrhythmias was the same in each group (3/23 cases) (p= 1.0). CONCLUSIONS: The
incidence of cardiac arrhythmias in this study did not appear to be influenced by
the nature of pre-anaesthetic medication. CLINICAL RELEVANCE: The incidence of
cardiac arrhythmias under halothane anaesthesia was 13% in this study.
Acepromazine did not appear to exert an anti-arrhythmic effect. This may not be
the case in a larger scale study.
PMID- 28404167
TI - A comparison of the 'Maxima' and the modified Ayre's T-piece breathing systems in
spontaneously breathing cats.
AB - OBJECTIVE: To compare the fresh gas flow requirements of the 'Maxima' and Jackson
Rees modified Ayre's T-piece (JRMATP) in spontaneously breathing anaesthetized in
cats. STUDY DESIGN: Prospective randomized clinical study. ANIMALS OR SAMPLE
POPULATION: Fifteen adult cats (6 male, 9 female, 3.1 +/- 0.4 kg [ x- +/- SD]).
MATERIALS & METHODS: After pre-anaesthetic medication with acepromazine and
pethidine, anaesthesia was induced using thiopentone and the trachea was
intubated with a cuffed endotracheal tube. This was attached to either a 'Maxima'
or a JRMATP breathing system; allocation was randomized. Anaesthesia was
maintained with halothane delivered in a 1 : 1 oxygen : nitrous oxide mixture.
Initial total fresh gas flow (FGF) was set at 600 mL kg-1 min-1. After 20
minutes, FGF was reduced in increments of 200 mL min-1 until rebreathing
(inspired CO2 concentration >0.2%) occurred. At this point, FGF was increased to
600 mL kg-1 and the process was repeated with the other breathing system. The
respiratory rate and airway pressure at the endotracheal tube connector were
monitored throughout anaesthesia. RESULTS: The mean fresh gas flow that prevented
rebreathing with the Maxima system (164 +/- 39 mL kg-1) was significantly less (p
< 0.0001) than that required in the modified T-piece (455 +/- 0.77 mL kg-1).
Respiratory rates and airway pressures at the endotracheal tube connector were
not significantly affected by breathing system employed. CONCLUSIONS: In terms of
the gas flow requirements that prevent rebreathing, the 'Maxima' breathing system
is more efficient than the modified Ayre's T-piece in spontaneously breathing
cats anaesthetised with halothane.
PMID- 28404168
TI - Comparison between isoflurane and sevoflurane anaesthesia in dogs.
PMID- 28404169
TI - Ketamine-guaiphenesin infusion to supplement halothane anaesthesia in horses.
PMID- 28404170
TI - Clinical signs of sevoflurane anaesthesia in spontaneously breathing rats.
PMID- 28404171
TI - Influence of sevoflurane and desflurane anaesthesia on blood biochemical values
in horses.
PMID- 28404172
TI - Effect of dexmedetomidine and medetomidine on isoflurane requirements in sheep
undergoing orthopaedic surgery.
PMID- 28404173
TI - The influence of morphine on the halothane sparing effect of xylazine: II,
xylazine and morphine plasma concentrations.
PMID- 28404174
TI - Cardiopulmonary responses during isoflurane anaesthesia in llamas.
PMID- 28404175
TI - Extradural anaesthesia using lidocaine, ropivacaine, hyperbaric lidocaine and a
combination of lidocaine and ropivacaine in mares.
PMID- 28404176
TI - Effect of fentanyl on minimum alveolar concentration of isoflurane in Rhesus
monkeys.
PMID- 28404177
TI - Clinical responses and plasma drug concentrations associated with different
infusions of xylazine and ketamine in horses.
PMID- 28404178
TI - Development of nociceptive threshold testing devices for evaluation of analgesics
in cats.
PMID- 28404179
TI - Incidence of gastro-oesophageal reflux during anaesthesia, following two
different fasting times in dogs.
PMID- 28404180
TI - Effects of guaiphenesin on the equine electroencephalogram during anaesthesia
with halothane in oxygen.
AB - OBJECTIVE: To identify and characterize the effects of guaiphenesin (GGE) on the
electroencephalogram during halothane anaesthesia. STUDY DESIGN: Prospective
controlled study. ANIMALS: Eight healthy Welsh mountain pony geldings between 5
and 9 years old and weighing between 270 and 330 kg (mean 301 kg). METHODS:
Anaesthesia was induced with thiopentone and maintained using halothane in
oxygen. End tidal halothane was maintained above 0.75 and below 0.85%. The EEG
was recorded continuously and a binaural broad band click stimulus was provided
throughout the experiment at 6.1224 Hz. An infusion of 1500 mg GGE was given over
5 minutes. Samples were taken for blood gas analysis and plasma GGE assay (HPLC)
5 minutes prior to the start of the infusion and at 3, 5, 7, 10, 15, 20, 30, 45
and 60 minutes thereafter. The median and 95th percentile of the EEG were
calculated using standard statistical techniques and the mid-latency of the
auditory evoked response was generated. The values of EEG variables at each time
point were compared to the average value for the 15 minute period before the
infusion was started. Arterial blood gas values and plasma GGE concentration were
compared to the baseline sample taken prior to the start of the infusion.
Comparisons were made using analysis of variance for repeated measures followed
by Dunnett's test if a significant difference was detected. RESULTS: The peak
serum plasma concentration was 49.6 +/- 7.8 MUg mL-1 (mean +/- SD) occurring five
minutes after the start of the infusion. The 95% spectral edge frequency (F95) of
the EEG decreased by a maximum of 5.2 +/- 14.3% 5 minutes after the start of the
GGE infusion. This change did not reach statistical significance (p= 0.07). When
three nonresponders were excluded, the depression in F95 at 5 minutes in the
remaining five animals became 13.0 +/- 12.0% and was statistically significant
(p= 0.02). No changes were seen in median frequency of the EEG or the second
differential of the middle latency auditory evoked potential. CONCLUSIONS: These
results did not demonstrate any statistically significant GGE-induced changes in
the EEG. However, there was some visible depression of F95 in five of the animals
studied even though the dose of GGE used was considerably less than that used in
most clinical circumstances. CLINICAL RELEVANCE: The EEG effects seen in this
study concur with the commonly held view that while GGE has some sedative
effects, it is not a reliable anaesthetic agent.
PMID- 28404181
TI - Propofol protects cell proteins against the oxidation induced by a simultaneous
generation of superoxide anion and nitric oxide.
PMID- 28404182
TI - Assessment of the Komesaroff machine for delivering sevoflurane to dogs.
PMID- 28404183
TI - Diminished platelet aggregation following intravenous propofol in pigs.
PMID- 28404184
TI - Correlation of pulse oximetry and capnometry with arterial blood gas analysis
during spontaneous and controlled ventilation in dogs.
PMID- 28404185
TI - Post-operative analgesia in cats: a comparison of racemic methadone, levo
methadone and dextromoramide.
PMID- 28404186
TI - Transvascular fluid dynamics.
AB - OBJECTIVE: To review the pathophysiology of fluid and macromolecular movement
between the microvascular, interstitial and lymphatic spaces and provide a basis
for logical intravenous colloid therapy. DATABASES USED: Medline (1966 -
present), Commonwealth Agricultural Bureaux abstracts (1973 - present) and
Personal files.
PMID- 28404187
TI - Hepatitis E: a neglected virus.
PMID- 28404188
TI - Postoperative thiopurines in smokers with Crohn's disease.
PMID- 28404189
TI - A new technique to improve surgery for peritoneal colorectal metastases?
PMID- 28404190
TI - Ventral mesh rectopexy for rectal prolapse: level-I evidence.
PMID- 28404191
TI - Tackling cancers of unmet need: the pancreatic cancer pathway.
PMID- 28404197
TI - Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after
surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled
trial.
AB - BACKGROUND: Up to 60% of patients with Crohn's disease need intestinal resection
within the first 10 years of diagnosis, and postoperative recurrence is common.
We investigated whether mercaptopurine can prevent or delay postoperative
clinical recurrence of Crohn's disease. METHODS: We did a randomised, placebo
controlled, double-blind trial at 29 UK secondary and tertiary hospitals of
patients (aged >16 years in Scotland or >18 years in England and Wales) who had a
confirmed diagnosis of Crohn's disease and had undergone intestinal resection.
Patients were randomly assigned (1:1) by a computer-generated web-based
randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight
rounded to the nearest 25 mg or placebo; patients with low thiopurine
methyltransferase activity received half the normal dose. Patients and their
carers and physicians were masked to the treatment allocation. Patients were
followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's
disease (Crohn's Disease Activity Index >150 plus 100-point increase in score)
and the need for anti-inflammatory rescue treatment or primary surgical
intervention. Primary and safety analyses were by intention to treat. Subgroup
analyses by smoking status, previous thiopurines, previous infliximab or
methotrexate, previous surgery, duration of disease, or age at diagnosis were
also done. This trial is registered with the International Standard Randomised
Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials
Database (EudraCT number 2006-005800-15). FINDINGS: Between June 6, 2008, and
April 23, 2012, 240 patients with Crohn's disease were randomly assigned: 128 to
mercaptopurine and 112 to placebo. All patients received at least one dose of
study drug, and no randomly assigned patients were excluded from the analysis. 16
(13%) of patients in the mercaptopurine group versus 26 (23%) patients in the
placebo group had a clinical recurrence of Crohn's disease and needed anti
inflammatory rescue treatment or primary surgical intervention (adjusted hazard
ratio [HR] 0.54, 95% CI 0.27-1.06; p=0.07; unadjusted HR 0.53, 95% CI 0.28-0.99;
p=0.046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine
group and 12 (46%) of 26 in the placebo group had a clinical recurrence that
needed treatment (HR 0.13, 95% CI 0.04-0.46), compared with 13 (13%) of 99 non
smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group
(0.90, 0.42-1.94; pinteraction=0.018). The effect of mercaptopurine did not
significantly differ from placebo for any of the other planned subgroup analyses
(previous thiopurines, previous infliximab or methotrexate, previous surgery,
duration of disease, or age at diagnosis). The incidence and types of adverse
events were similar in the mercaptopurine and placebo groups. One patient on
placebo died of ischaemic heart disease. Adverse events caused discontinuation of
treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%)
of 112 in the placebo group. INTERPRETATION: Mercaptopurine is effective in
preventing postoperative clinical recurrence of Crohn's disease, but only in
patients who are smokers. Thus, in smokers, thiopurine treatment seems to be
justified in the postoperative period, although smoking cessation should be
strongly encouraged given that smoking increases the risk of recurrence. FUNDING:
Medical Research Council.
PMID- 28404198
TI - Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal
origin: a single-centre feasibility study.
AB - BACKGROUND: Optimum cytoreductive surgery combined with hyperthermic
intraperitoneal chemotherapy (HIPEC) is essential for the curative treatment of
peritoneal carcinomatosis of colorectal origin. At present, surgeons depend on
visual inspection and palpation for tumour detection. Improved detection of
tumour tissue using molecular fluorescence-guided surgery could not only help
attain a complete cytoreduction of metastatic lesions, but might also prevent
overtreatment by avoiding resection of benign lesions. METHODS: For this non
randomised, single-centre feasibility study, we enrolled patients with colorectal
peritoneal metastases scheduled for cytoreductive surgery and HIPEC. 2 days
before surgery, 4.5 mg of the near-infrared fluorescent tracer bevacizumab
IRDye800CW was administered intravenously. The primary objectives were to
determine the safety and feasibility of molecular fluorescence-guided surgery
using bevacizumab-IRDye800CW. Molecular fluorescence-guided surgery was deemed
safe if no allergic or anaphylactic reactions were recorded and no serious
adverse events were attributed to bevacizumab-IRDye800CW. The technique was
deemed feasible if bevacizumab-IRDye800CW enabled detection of fluorescence
signals intraoperatively. Secondary objectives were correlation of fluorescence
with histopathology by back-table imaging of the fresh surgical specimen and semi
quantitative ex-vivo analyses of formalin-fixed paraffin embedded (FFPE) tissue
on all peritoneal lesions. Additionally, VEGF-alpha staining and fluorescence
microscopy was done. This study is registered with the Netherlands Trial
Registry, number NTR4632. FINDINGS: Between July 3, 2014, and March 2, 2015,
seven patients were enrolled in the study. One patient developed an abdominal
sepsis 5 days postoperatively and another died from an asystole 4 days
postoperatively, most probably due to a cardiovascular thromboembolic event.
However, both serious adverse events were attributed to the surgical
cytoreductive surgery and HIPEC procedure. No serious adverse events related to
bevacizumab-IRDye800CW occurred in any of the patients. Intraoperatively,
fluorescence was seen in all patients. In two patients, additional tumour tissue
was detected by molecular fluorescence-guided surgery that was initially missed
by the surgeons. During back-table imaging of fresh surgical specimens, a total
of 80 areas were imaged, marked, and analysed. All of the 29 non-fluorescent
areas were found to contain only benign tissue, whereas tumour tissue was
detected in 27 of 51 fluorescent areas (53%). Ex-vivo semi-quantification of 79
FFPE peritoneal lesions showed a tumour-to-normal ratio of 6.92 (SD 2.47).
INTERPRETATION: Molecular fluorescence-guided surgery using the near-infrared
fluorescent tracer bevacizumab-IRDye800CW is safe and feasible. This technique
might be of added value for the treatment of patients with colorectal peritoneal
metastases through improved patient selection and optimisation of cytoreductive
surgery. A subsequent multicentre phase 2 trial is needed to make a definitive
assessment of the diagnostic accuracy and the effect on clinical decision making
of molecular fluorescence-guided surgery. FUNDING: FP-7 Framework Programme
BetaCure and SurgVision BV.
PMID- 28404199
TI - Bowel function after laparoscopic posterior sutured rectopexy versus ventral mesh
rectopexy for rectal prolapse: a double-blind, randomised single-centre study.
AB - BACKGROUND: Laparoscopic ventral mesh rectopexy for rectal prolapse has been
widely used over the past decade to reduce postoperative functional bowel
disorders. We aimed to compare changes in functional outcome 12 months after
laparoscopic ventral mesh rectopexy versus laparoscopic posterior sutured
rectopexy in patients with rectal prolapse. METHODS: In this double-blind,
randomised trial, consecutive patients aged 18 years or older at a single centre
in Denmark with full-thickness rectal prolapse were randomly assigned (1:1) to
either laparoscopic ventral mesh rectopexy or laparoscopic posterior sutured
rectopexy by drawing numbers from opaque envelopes, in blocks of four for
patients with or without preoperative constipation. Functional assessment was
done preoperatively and 12 months postoperatively. The primary outcome was
preoperative-to-postoperative change in obstructed defecation syndrome (ODS)
score. Patients and those assessing the outcomes were masked to the procedure.
The primary analysis was done in the per-protocol population. Safety outcomes
were assessed in the entire cohort. The trial is registered with
ClinicalTrials.gov, number NCT00946205. FINDINGS: From Nov 1, 2006, to Jan 31,
2014, 75 consecutive patients were assigned to laparoscopic posterior sutured
rectopexy (n=37) or laparoscopic ventral mesh rectopexy (n=38). Eight patients
withdrew consent to follow-up, leaving 34 patients in the posterior sutured
rectopexy group and 33 in the ventral mesh rectopexy groups for the primary
analysis. The preoperative-to-postoperative reduction in ODS score was 1.97 (95%
CI 0.01 to 3.93) in patients who received ventral mesh rectopexy and 2.18 (-0.14
to 4.49) in those who received posterior sutured rectopexy (difference -0.21 [
3.19 to 2.78]; p=0.890). Postoperative surgical complications of Clavien-Dindo
grade II or worse were reported in one (3%) of 38 patients in the ventral mesh
rectopexy group (ureteral injury resulting in urine leakage, and a psoas abscess)
and one (3%) of 37 patients in the posterior sutured rectopexy group (haematoma
and pelvic abscess). Two (5%) patients in the posterior sutured rectopexy group
developed recurrence within 12 months compared with none in the ventral mesh
rectopexy group (p=0.305). INTERPRETATION: Functional outcome measured by
preoperative-to-postoperative change in ODS score was not significantly superior
in patients who underwent ventral mesh rectopexy compared with those who had
posterior sutured rectopexy. Additional, large, randomised, multicentre studies
with long-term outcomes are warranted. FUNDING: None.
PMID- 28404200
TI - Symptoms and patient factors associated with diagnostic intervals for pancreatic
cancer (SYMPTOM pancreatic study): a prospective cohort study.
AB - BACKGROUND: Pancreatic cancer is the tenth most common cancer in the UK; however,
outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms
and other clinical and sociodemographic factors associated with pancreatic cancer
diagnosis and diagnostic intervals. METHODS: We did this prospective cohort study
at seven hospitals in two regions in England. We recruited participants aged 40
years or older who were referred for suspicion of pancreatic cancer. Data were
collected by use of a patient questionnaire and primary care and hospital
records. Descriptive and regression analyses were done to examine associations
between symptoms and patient factors with the total diagnostic interval (time
from onset of the first symptom to the date of diagnosis), comprising patient
interval (time from first symptom to first presentation) and health system
interval (time from first presentation to diagnosis). FINDINGS: We recruited 391
participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%)
participants were diagnosed with pancreatic cancer (41 [34%] had metastatic
disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%)
patients had multiple first symptoms whereas 161 (41%) patients had a solitary
first symptom. In this referred population, no initial symptoms were reported
more frequently by patients with cancer than by those with no cancer. Several
subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105
patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer;
p<0.0001), fatigue (48/95 [51%] vs 40/155 [26%]; p=0.0001), change in bowel habit
(36/87 [41%] vs 28/175 [16%]; p<0.0001), weight loss (55/100 [55%] vs 41/184
[22%]; p<0.0001), and decreased appetite (41/86 [48%] vs 41/156 [26%]; p=0.0011).
There was no difference in any interval between patients with pancreatic cancer
and those with no cancer (total diagnostic interval: median 117 days [IQR 57-234]
vs 131 days [IQR 66-284]; p=0.32; patient interval 18 days [0-37] vs 15 days [1
62]; p=0.22; health system interval 76 days [28-161] vs 79 days [30-156];
p=0.68). Total diagnostic intervals were shorter when jaundice (hazard ratio [HR]
1.38, 95% CI 1.07-1.78; p=0.013) and decreased appetite (1.42, 1.11-1.82;
p=0.0058) were reported as symptoms, and longer in patients presenting with
indigestion (0.71, 0.56-0.89; p=0.0033), back pain (0.77, 0.59-0.99; p=0.040),
diabetes (0.71, 0.52-0.97; p=0.029), and self-reported anxiety or depression, or
both (0.67, 0.49-0.91; p=0.011). Health system intervals were likewise longer
with indigestion (0.74, 0.58-0.95; p=0.0018), back pain (0.76, 0.58-0.99;
p=0.044), diabetes (0.63, 0.45-0.89; p=0.0082), and self-reported anxiety or
depression, or both (0.63, 0.46-0.88; p=0.0064), but were shorter with male sex
(1.41, 1.1-1.81; p=0.0072) and decreased appetite (1.56, 1.19-2.06; p=0.0015).
Weight loss was associated with longer patient intervals (HR 0.69, 95% CI 0.54
0.89; p=0.0047). INTERPRETATION: Although we identified no initial symptoms that
differentiated people diagnosed with pancreatic cancer from those without
pancreatic cancer, key additional symptoms might signal the disease. Health-care
professionals should be vigilant to the possibility of pancreatic cancer in
patients with evolving gastrointestinal and systemic symptoms, particularly in
those with diabetes or mental health comorbidities. FUNDING: National Institute
for Health Research and Pancreatic Cancer Action.
PMID- 28404201
TI - Globalisation of inflammatory bowel disease: perspectives from the evolution of
inflammatory bowel disease in the UK and China.
AB - The UK and China provide unique historical perspectives on the evolution of the
incidence of inflammatory bowel disease, which might provide insight into its
pathogenesis. Historical records from the UK document the emergence of ulcerative
colitis during the mid-1800s, which was later followed by the recognition of
Crohn's disease in 1932. During the second half of the 20th century, the
incidence of inflammatory bowel disease rose dramatically in high-income
countries. Globalisation at the turn of the 21st century led to rapid economic
development of newly industrialised countries such as China. In China, the
modernisation of society was accompanied by the recognition of a sharp rise in
the incidence of inflammatory bowel disease. The prevalence of inflammatory bowel
disease is expected to continue to rise in high-income countries and is also
likely to accelerate in the developing world. An understanding of the shared and
different environmental determinants underpinning the pathogenesis of
inflammatory bowel disease in western and eastern countries is essential to
implement interventions that will blunt the rising global burden of inflammatory
bowel disease.
PMID- 28404202
TI - Hepatitis C treatment as prevention: evidence, feasibility, and challenges.
AB - The advent of interferon-free direct-acting antiviral therapy for hepatitis C
virus (HCV) infection has heightened discussion of treatment as prevention. Rapid
scale-up in many settings, and the prospect of further treatment simplification
have extended therapeutic optimism towards HCV elimination. However, questions
remain regarding the feasability of HCV treatment as prevention, including real
world efficacy of direct-acting antiviral therapy, particularly among people who
inject drugs, and whether expanded treatment access will be sufficient to reduce
HCV transmission. HCV re-infection among both people who inject drugs and HIV
infected men who have sex with men might also compromise the benefits of HCV
treatment as prevention. Empirical studies of HCV treatment as prevention are
ongoing, including among community-based people who inject drugs, prisoners, and
HIV-infected individuals. Some national HCV elimination programmes have also been
established. Key requirements to optimise benefits of HCV treatment as prevention
will include enhanced HCV diagnosis and linkage to care, high-coverage harm
reduction, drug price reform, and removal of liver disease and drug use-based
restrictions to treatment access.
PMID- 28404203
TI - Antifibrotics in chronic liver disease: tractable targets and translational
challenges.
AB - Chronic liver disease prevalence is increasing globally. Iterative liver damage,
secondary to any cause of liver injury, results in progressive fibrosis,
disrupted hepatic architecture, and aberrant regeneration, which are defining
characteristics of liver cirrhosis. Liver transplantation is an effective
treatment for end-stage liver disease; however, demand greatly outweighs donor
organ supply, and in many parts of the world liver transplantation is
unavailable. Hence, effective antifibrotic therapies are urgently required. In
the past decade, rapid progress has been made in our understanding of the
pathophysiology of liver fibrosis and a large number of potential cellular and
molecular antifibrotic targets have been identified. This has led to numerous
clinical trials of antifibrotic agents in patients with chronic liver disease.
However, none of these have resulted in a robust and reproducible effect on
fibrosis. It is therefore imperative that the ongoing translational challenges
are addressed, to convert scientific discoveries into potent antifibrotics and
enable bridging of the translational gap between putative therapeutic targets and
effective treatments for patients with chronic liver disease.
PMID- 28404204
TI - Global surgical electives in residency: The impact on training and future
practice.
AB - BACKGROUND: The purpose of this study was to evaluate perceptions regarding the
value of global surgical electives (GSEs) and pursuit of a career in global
surgery amongst residents and surgeons. METHODS: We sent an anonymous
questionnaire to all current and former surgical residents of our tertiary-care,
university-based institution from the years 2000-2013. Questions addressed the
experience and value of practicing surgery in low or middle income countries
(LMIC) in residency and as a career. RESULTS: Twenty-three (40%) graduates (G)
and 36 (84%) surgical residents (R) completed the survey. Thirteen residents
(36%) and 13 (52%) graduates had delivered surgical care in a LMIC. Respondents
stated that their experience positively impacted patient care (G = 80% vs R =
75%) and learning (G = 75% vs R = 90%). Of the 4 graduates still working in a
LMIC, the majority (75%) were providing less than 2 months of care. Logistical
reasons and family obligations were the most common barriers (n = 13).
CONCLUSION: Few graduates are able to incorporate global surgery into their
practice despite interest. For enduring participation, logistical and family
support is needed.
PMID- 28404205
TI - Circumferential pedicled omental flap for protection of portomesenteric venous
reconstruction and gastroduodenal artery stump following pancreatoduodenectomy.
PMID- 28404206
TI - Farming and ranching related injuries in Southern Idaho.
AB - INTRODUCTION: Agriculture is an inherently dangerous industry. We sought injury
data for use with the Idaho Time Sensitive Emergency (TSE) system to formulate
goals and track improvements. METHODS: Registries in southern Idaho were queried
for ICD-9-CM diagnoses related to agriculture in 2014. Injuries known or likely
to have occurred on properties intended for farming, ranching, animal care, or
milk production, and relating to those activities were included. RESULTS: Among
72 patients, injuries were related to horses (31%), machinery (17%), ATVs (17%),
and hay bales/haystacks (13%). Average age was 45 (3-82), 82% male, and mean ISS
of 13 (1-50). Transportation utilized air (31%) and ground (69%) methods, with an
average of 35 min (9-132). There was 1 inhospital death and 4 on-scene
fatalities. CONCLUSIONS: We established baseline transport and injury data for
the Idaho TSE system. These results can help our TSE system track improvements
intended to increase quality of care.
PMID- 28404207
TI - Moral alchemy: How love changes norms.
AB - We discuss a process by which non-moral concerns (that is concerns agreed to be
non-moral within a particular cultural context) can take on moral content. We
refer to this phenomenon as moral alchemy and suggest that it arises because
moral obligations of care entail recursively valuing loved ones' values, thus
allowing propositions with no moral weight in themselves to become morally
charged. Within this framework, we predict that when people believe a loved one
cares about a behavior more than they do themselves, the moral imperative to care
about the loved one's interests will raise the value of that behavior, such that
people will be more likely to infer that third parties will see the behavior as
wrong (Experiment 1) and the behavior itself as more morally important
(Experiment 2) than when the same behaviors are considered outside the context of
a caring relationship. The current study confirmed these predictions.
PMID- 28404208
TI - Predictors of physicians' communication performance in a decision-making
encounter with a simulated advanced-stage cancer patient: A longitudinal study.
AB - OBJECTIVES: Physicians' characteristics that influence their communication
performance (CP) in decision-making encounters have been rarely studied. In this
longitudinal study, predictors of physicians' CP were investigated with a
simulated advanced-stage cancer patient. METHODS: Physicians (n=85) performed a
decision-making encounter with a simulated patient (SP). Their CP was calculated
by analyzing encounter transcripts with validated interaction analysis systems.
Potential specific psychological predictors were physicians' empathy towards the
SP (Jefferson Scale of Physician Empathy, JSPE) and their decisional conflict
about the treatment (Decisional Conflict Scale, DCS). Potential general
psychological predictors were physicians' empathy towards cancer patients (JSPE),
their decisional conflict about cancer patients' treatments (DCS), and their
affective reactions to uncertainty (Physicians' Reactions to Uncertainty, PRU).
RESULTS: Physicians' CP was predicted by their decisional conflict about the SP's
treatment (DCS) (beta=0.41; p< 0.001) and their affective reactions to
uncertainty regarding cancer treatments (PRU) (beta=-0.31; p=0.003). CONCLUSION:
During encounters with advanced-stage cancer patients, physicians' awareness of
uncertainty about which treatments to consider may facilitate their communication
performance, whereas physicians' affective reactions to uncertainty may inhibit
their performance. PRACTICE IMPLICATIONS: Physicians' decisional conflict and
reactions to uncertainty should be addressed in communication skills training
programs.
PMID- 28404209
TI - Investigation of Toxoplasma gondii in semen, testicle and epididymis tissues of
primo-infected cats (Felis catus).
AB - This study aimed to investigate the presence of Toxoplasma gondii in semen,
testicle and epididymis tissues of cats experimentally infected by this
coccidium. A total of 12 male felines without a definite breed that were of
reproductive age and serologically negative for T. gondii were selected and
distributed to the following three experimental groups: GI, inoculated with 600
tissue cysts of the P strain of T. gondii (isolate III); GII, inoculated with
2*105 tachyzoites of the RH strain (isolate I); and GIII, not inoculated (control
group). Prior to inoculation (day -7 and 0) and on post inoculation days (PIDs)
7, 14, 21, 28, 42, 56, and 70, all felines were subjected to assessments of anti
T. gondii IgG by indirect immunofluorescence (IIF) and assessments of
parasitemia. Collection of semen (electroejaculation) was performed on the
specified dates, followed by nested PCR and bioassays in mice to detect T.
gondii. On PID 70, all 12 felines were orchiectomized, and the presence of the
parasite in the testicles and epididymides was evaluated by nested PCR, murine
bioassay, and histopathological and immunohistochemical analyses. All felines
inoculated with T. gondii (GI and GII) seroconverted to the toxoplasmic infection
after PID 14; on PID 7, seroconversion of three felines (P4, RH2 and RH4) could
observed, and all exhibited detectable titers by PID 64. The GII felines
exhibited greater serological titers compared with GI felines. The maximum
serological titer (IgG) was observed in feline RH3 (titer 1024), while in other
experimental felines, a maximum titer of 256 was detected. Parasitemic peaks were
diagnosed in all felines of groups I and II from PIDs 7-42. A total of five
parasitemic peaks were diagnosed in GI and nine in GII. In none of the
experimental time points was the presence of T. gondii diagnosed in seminal
samples collected from the felines or in the testicle or epididymis tissues
collected from these animals. Thus, sexual transmission in domestic cats does not
appear to be a major route of T. gondii infection, possibly demonstrating the
tendency of this protozoan to develop a response directed to the formation and
excretion of oocysts in the feces of these definite hosts, which act as its main
route of perpetuation in the environment.
PMID- 28404211
TI - Intraoperative real-time assessment of blood flow using indocyanine green
angiography after anastomoses in free-flap reconstructions.
PMID- 28404212
TI - Potential of autogenous or fresh-frozen allogeneic bone block grafts for bone
remodelling: a histological, histometrical, and immunohistochemical analysis in
rabbits.
AB - Our aim was to compare the wound healing of autogenous bone grafts with that of
fresh-frozen allogeneic block bone in rabbits. We used 25 animals. One was killed
before the experiment to provide the allogeneic bone, and the remainder were
killed at four time points (n=6 in each group). On histometrical analysis there
was a significant difference between the two groups only at 45days and between 15
and 45days in the intergroup analysis. However, there was significantly more
revascularisation (p<0.05), resorption (p<0.05), and bony replacement (p<0.05) in
the autogenous group in the immunohistochemical analysis. In later periods, the
autogenous bone was replaced by newly-formed bone in all samples, whereas it was
always possible to find regions of devitalised bone in the fresh-frozen
allogeneic bone grafts. Autogenous grafts were completely replaced whereas, in
the fresh- frozen allogeneic grafts, we found acellular tissue that had been
incorporated into the receptor bed interface during the later evaluation times.
PMID- 28404210
TI - Characteristics of epilepsy in patients with Kabuki syndrome with KMT2D
mutations.
AB - BACKGROUND: The characteristics of epilepsy in patients with Kabuki syndrome with
KMT2D mutations (KABUK1) have not yet been well documented. This is the first
review to explore this. MATERIALS & METHODS: We enrolled 14 patients with KABUK1,
whose median age was 13.6years (range=4.1-21.3years). Their medical records from
October 1981 to May 2016 were retrospectively analyzed. RESULTS: Epilepsy was
present in 5 (36%) patients. Four of these patients presented with nonsense
mutations and one with missense mutations. None presented with brain
abnormalities. Four patients presented with annual or monthly focal seizures, of
which three evolved to bilateral convulsive seizures. Median onset age of focal
epilepsy was 11.8years (range=9.5-12.8years). One presented with monthly
myoclonic seizures from age 11.2, whose mother with no other KABUK1 features, had
focal epilepsy. The cumulative incidence of epilepsy related to KABUK1 up until
age 13 was 45%. Interictal electroencephalogram revealed focal paroxysmal
epileptiform discharges (in frontal, central, and parietal regions) in three
patients, diffuse high-voltage spike-and-waves in one patient, and normal sleep
record in one patient. Myoclonic seizures were rapidly controlled by
levetiracetam. In contrast, focal seizures were not controlled in the early
period of antiepileptic therapy. CONCLUSION: This long-term follow-up of patients
with KABUK1 revealed a higher prevalence of epilepsy than previously reported.
The age of epilepsy onset and rate of focal seizures evolving to bilateral
convulsive seizures in KABUK1 were also higher than previously reported in
patients with clinically diagnosed Kabuki syndrome. Although seizure outcome is
reported to be favorable in Kabuki syndrome, focal seizures in patients with
KABUK1 were not immediately responsive to medication.
PMID- 28404213
TI - Comparison of C-MAC, McGrath and Macintosh laryngoscope use in a standardized
airway manikin with immobilized cervical spine by novice intubators.
PMID- 28404214
TI - Comparing performance of Macintosh and Intubrite laryngoscopes for intubation.
PMID- 28404215
TI - Performance of an outpatient stress testing protocol for low risk chest pain
patients presenting to the emergency department.
PMID- 28404216
TI - Lung ultrasonography to diagnose pneumothorax of the newborn.
AB - OBJECTIVE: To explore the reliability and accuracy of lung ultrasound for
diagnosing neonatal pneumothorax. METHODS: This study was divided into two
phases. (1) In the first phase, from January 2013 to June 2015, 40 patients with
confirmed pneumothorax had lung ultrasound examinations performed to identify the
sonographic characteristics of neonatal pneumothorax. (2) In the second phase,
from July 2015 to August 2016, lung ultrasound was undertaken on 50 newborn
infants with severe lung disease who were suspected of having pneumothorax, to
evaluate the sonographic accuracy and reliability to diagnose pneumothorax.
RESULTS: (1) The main ultrasonic manifestations of pneumothorax are as follows: 1
lung sliding disappearance, which was observed in all patients (100%); 2 the
existence of the pleural line and the A-line, which was also observed in all
patients (100%); 3 the lung point, which was found in 75% of the infants with
mild-moderate pneumothorax but not found to exist in 25% of the severe
pneumothorax patients; 4 the absence of B-lines in the area of the pneumothorax
(100% of the pneumothorax patients); and 5 no lung consolidation existed in the
area of the pneumothorax (100% of the pneumothorax patients). (2) The accuracy
and reliability of the lung sonographic signs of lung sliding disappearance as
well as the existence of the pleural line and the A-line in diagnosing
pneumothorax were as follows: 100% sensitivity, 100% specificity, 100% positive
predictive value, and 100% negative predictive value. When the lung point exists,
the diagnosis is mild-moderate pneumothorax, whereas if no lung point exists, the
diagnosis is severe pneumothorax. CONCLUSION: Lung ultrasound is accurate and
reliable in diagnosing and ruling out neonatal pneumothorax and, in our study,
was found to be as accurate as chest X-ray.
PMID- 28404217
TI - Children's expectations about conventional and moral behaviors of ingroup and
outgroup members.
AB - Although children demonstrate robust social preferences for ingroup members early
in ontogeny, it is not yet clear whether these preferences are based on children
generally liking people who are more familiar or on children holding specific
biased beliefs about people in their ingroup as compared with people in their
outgroup. Here, we investigated the origins of humans' propensity to link ingroup
members with positive behaviors and outgroup members with negative behaviors by
asking whether linguistic group membership influences children's expectations of
how people will act. Our findings indicate that the effect of group membership on
children's expectations about other people's actions varies across both domain
(moral and conventional) and age. Whereas all children in our study (3- to 11
year-olds) expected ingroup members to be more likely to conform to social
conventions and expected outgroup members to be more likely to break conventional
rules, only older children (7- to 11-year-olds) used social group membership to
form expectations about which people would be more likely to act morally versus
immorally. Thus, younger children do not automatically form biased character
judgments based on group membership, although they do understand that social
group membership is particularly relevant for reasoning about which people will
be more likely to act in line with social norms.
PMID- 28404218
TI - Association between pediatric blunt splenic injury volume and the splenectomy
rate.
AB - BACKGROUND/PURPOSE: While pediatric trauma centers are shown to have lower
splenectomy rate as compared to adult trauma centers, it remains unknown whether
other institutional factors such as case volumes would have an impact on the
splenectomy rate in pediatric blunt splenic injury (BSI). METHODS: Pediatric
patients who sustained BSI were identified from the National Trauma Data Bank
2007-2014. A hierarchical logistic regression model was built to evaluate
differences in risk-adjusted splenectomy rate and in-hospital mortality in
between trauma centers with different pediatric BSI case volumes. RESULTS: A
total of 7621 children who met criteria were treated at trauma centers with
different pediatric BSI case volumes (0-60, 61-120, 121-180, 181-240 cases during
2007-2014 for Group 1, 2, 3, and 4, respectively). High volume centers were shown
to have decreased splenectomy rates (odds ratios [OR] 0.50 and 0.64, 95%
confidence intervals [CI] 0.30-0.83, 0.44-0.95 for Groups 3 and 4, respectively)
with an additional survival benefit in Group 4 (OR 0.452, 95%CI 0.257-0.793) when
compared to the lowest volume centers (Group 1). CONCLUSIONS: Higher pediatric
BSI case volume was associated with lower splenectomy rate with an additional
survival benefit. Trauma centers' volume in pediatric BSI may be an important
factor for the improved splenic preservation. LEVEL OF EVIDENCE: Retrospective
comparative study, Level III.
PMID- 28404219
TI - Reply to: "In HIV/HCV co-infected patients T regulatory and myeloid derived
suppressor cells persist after successful treatment with directly acting
antivirals".
PMID- 28404220
TI - Agenesis of the retro-hepatic inferior vena cava.
PMID- 28404221
TI - Mantle Cell Lymphoma: Contemporary Diagnostic and Treatment Perspectives in the
Age of Personalized Medicine.
AB - Mantle cell lymphoma is a clinically heterogeneous disease occurring within a
heterogeneous patient population, highlighting a need for personalized therapy to
ensure optimal outcomes. It is therefore critical to understand the benefits and
risks associated with both intensive and deintensified approaches. In the
following review we provide a therapeutic roadmap to strategically guide
treatment for newly diagnosed and relapsed/refractory patients highlighting
pivotal and recently published results involving known and novel therapies.
PMID- 28404222
TI - The effect of different extraction techniques on property and bioactivity of
polysaccharides from Dioscorea hemsleyi.
AB - The rhizoma of Dioscorea hemsleyi (DH) has been used as a treatment of diabetes
in China for hundreds of years. Polysaccharides in DH were extracted by using
ultrasonic-assisted extraction (UAE), cold water extraction (CWE), warm water
extraction (WWE) and hot water extraction (HWE), separately. Then the different
characterizations of four DH polysaccharide (DHP) samples were analyzed by high
performance liquid chromatography (HPLC), high-performance Gel permeation
chromatography (HGPC), ultraviolet-visible spectroscopy(UV), fourier transform
infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Their
activities in vitro of DHP were compared. Experimental results showed that HWE
had the highest yield and large molecular weight. CWE had the highest uronic acid
yield and little molecular weight, and its DPPH, AGI and AAI activity were the
best. The molecular weight of UAE was small, and its RP and FRAP activity were
the best. Four DHP samples had differences in the surface topography, while they
all had the typical IR spectra characteristic of polysaccharides. According the
correlation analysis, it showed that the more uronic acid and the lower molecular
weight was, the higher the antioxidant activity was. The high content of
monosaccharide composition of Xyl, Ara, GlcA and GalA, and little molecular
weight have good effect on antidiabetic activity.
PMID- 28404224
TI - Regarding 'Clinical assessment of subacromial shoulder impingement - Which
factors differ from the asymptomatic population?' authored by Land et al.,
Musculoskeletal Science & Practice 27 (2017), 49-56.
PMID- 28404223
TI - Standardization of biopolymer production from seaweed associative bacteria.
AB - Polyhydroxyalkanoate (PHA) is the biodegradable plastic, which is shown the
similar properties to the synthetic plastic. Production of PHA is expensive when
compared with petrochemical based plastics costs and also hazardous to ecosystem.
In order to overcome these drawbacks, some cheaper commercially available carbon
sources like rice bran, coconut cake, palm jaggary, etc. can be used. The present
study aimed to identify the potential PHA producing bacterial strains from
different seaweeds. Based on PHA production and crotonic acid assay, two
bacterial strains were screened and designated as M3 and S6 which were found to
be efficient PHA producers. Potential PHA producers of M3 and S6 were identified
as Bacillus cereus RBL6 and Pseudomonas pseudoalcaligens RBL7 by 16S rRNA gene
sequencing. The physical and nutritional parameters such as pH, temperature,
incubation period, substrate, carbon and nitrogen concentration have been used
for enhancing PHA production which was served as precursor. The purified PHA had
been chemically characterized by FT-IR, GC-MS and viewed through SEM.
PMID- 28404225
TI - Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its
virion host shutoff protein.
AB - Cholesterol 25-hydroxylase (Ch25h) is an interferon-inducible protein, and recent
studies have demonstrated that it inhibited the replication of many enveloped
viruses. However, in this study, we found that cells infected with wild-type (WT)
HSV-1 reduced the expression of Ch25h, and ectopic expression of Ch25h could not
inhibit the replication of WT-HSV-1. By screening assay, HSV-1 UL41 protein was
found to down-regulate the expression of Ch25h. In addition, UL41 abrogated the
antiviral activity of Ch25h via degrading its mRNA. Furthermore, ectopic
expression of Ch25h inhibited the replication of UL41-null mutant HSV-1 (R2621),
but not WT-HSV-1, and knockdown of Ch25h did not affect the replication of WT-HSV
1, but promoted the replication of the R2621. For the first time, HSV-1 UL41 was
demonstrated to evade the antiviral function of Ch25h via its endonuclease
activity.
PMID- 28404226
TI - Percutaneous balloon pericardiotomy: Treatment of choice in patients with
advanced oncological disease and severe pericardial effusion.
AB - INTRODUCTION AND OBJECTIVES: Malignant pericardial effusion has a high recurrence
rate after pericardiocentesis. We sought to confirm the efficacy and feasibility
of percutaneous balloon pericardiotomy (PBP) as the initial treatment of choice
for these effusions. METHODS: Retrospective analysis of the clinical,
echocardiographic, and follow-up characteristics of a consecutive series of PBP
carried out in a single-center in patients with advanced cancer. RESULTS: Forty
PBPs were performed in 35 patients with a mean age of 61.8years (55% females).
Thirty-four patients had pathologically confirmed metastatic neoplastic disease
(26 patients with tumoral cells in the pericardial liquid), 7 had previously
required pericardiocentesis, and in the remaining patients PBP was the first
treatment for the effusion. All patients had a severe circumferential effusion
(29mm by mean on transthoracic echocardiography [TTE]), and most presented
evidence of hemodynamic compromise on TTE. In all cases, the procedure was
successful, there were no acute complications, and it was well tolerated at the
first attempt. There were no infectious complications during follow-up. One
patient developed a pseudoaneurysm in the right ventricle, even though no further
treatment was required. Eight patients needed a new pericardial procedure: 3 had
elective pericardial window surgeries and 5 had a second PBP. Eighty percent of
patients died during follow-up (57days by mean from the PBP) regarding their
oncological disease. CONCLUSION: PBP is a simple and safe technique that can be
effective in the prevention of recurrence in many patients with severe malignant
pericardial effusion. The characteristics of this procedure make it particularly
useful in this group of patients to avoid more aggressive, poorly tolerated
approaches, since they have a very poor prognosis regarding to their oncological
disease.
PMID- 28404227
TI - Multivessel stent thrombosis with optical coherence tomography (OCT) utilization
for therapeutic guidance.
AB - A 63 year old male presents with anterior ST elevation myocardial infarction. Two
years prior he had PCI with DES to the proximal left anterior descending (LAD)
and circumflex arteries following an abnormal stress test. Clopidogrel was
discontinued several weeks prior to this presentation.
PMID- 28404228
TI - Dynamic light scattering: A fast and reliable method to analyze bacterial growth
during the lag phase.
AB - A comparison between plate counting (PC) and dynamic light scattering (DLS) is
reported. PC is the standard technique to determine bacterial population as a
function of time; however, this method has drawbacks, such as the cumbersome
preparation and handling of samples, as well as the long time required to obtain
results. Alternative methods based on optical density are faster, but do not
distinguish viable from non-viable cells. These inconveniences are overcome by
using DLS. Two different bacteria strains were considered: Escherichia coli and
Staphylococcus aureus. DLS was performed at two different illuminating
conditions: continuous and intermittent. By the increment of particle size as a
function of time, it was possible to observe cell division and the formation of
aggregates containing very few bacteria. The scattered intensity profiles showed
the lag phase and the transition to the exponential phase of growth, providing a
quantity proportional to viable bacteria concentration. The results revealed a
clear and linear correlation in both lag and exponential phase, between the
Log10(colony-forming units/mL) from PC and the Log10 of the scattered intensity
Is from DLS. These correlations provide a good support to use DLS as an
alternative technique to determine bacterial population.
PMID- 28404229
TI - "We don't know. We've never had anybody like you before": Barriers to perinatal
care for women with physical disabilities.
AB - BACKGROUND: While more women with physical disabilities are becoming mothers,
many encounter barriers to perinatal care and experience poor outcomes. Little is
known about the perinatal care experiences and outcomes of women with physical
disabilities in Canada. OBJECTIVE: This qualitative study sought to understand
the perinatal care experiences and outcomes of women with physical disabilities
in one Canadian province, with an emphasis on identifying barriers to care.
METHODS: In-depth interviews were conducted with 13 women with physical
disabilities who had given birth in the last 5 years. Follow-up interviews were
conducted with 10 of the 13 participants. All interviews were audio-recorded and
transcribed verbatim. Data analysis was informed by a constructivist grounded
theory approach. RESULTS: Based on analysis of participants' interviews, five
themes regarding barriers to care were identified: (1) Inaccessible care
settings, (2) Negative attitudes, (3) Lack of knowledge and experience, (4) Lack
of communication and collaboration among providers, and (5) Misunderstandings of
disability and disability-related needs. CONCLUSIONS: Study findings reveal that
the perinatal care system is not set up with women with physical disabilities in
mind and that barriers to perinatal care may contribute to poor outcomes. More
research and training are needed to address barriers to perinatal care for women
with physical disabilities. Collaboration among perinatal and disability-related
providers and meaningful inclusion of women with physical disabilities in
educational initiatives and care plans are vital to improve care experiences and
outcomes.
PMID- 28404230
TI - Birth outcomes among US women with intellectual and developmental disabilities.
AB - BACKGROUND: Women with intellectual and developmental disabilities (IDD) are
bearing children at increasing rates. However, there is very little research
about pregnancy experiences and birth outcomes among women with IDD. No studies
to date have examined birth outcomes with a US population-based sample.
OBJECTIVE: The main objective was to estimate the national occurrence of
deliveries in women with IDD and to compare their birth outcomes to women without
IDD. METHODS: We examined the 2007-2011 Nationwide Inpatient Sample of the
Healthcare Cost and Utilization Project to compare birth outcomes in women with
and without IDD. Birth outcomes included preterm birth, low birth weight, and
stillbirth. Multivariable regression analyses compared birth outcomes between
women with and without IDD controlling for race/ethnicity, maternal age,
household income, health insurance status and type, comorbidity, region and
hospital location, teaching status, ownership, and year. RESULTS: Of an estimated
20.6 million deliveries identified through the HCUP 2007-2011 data 10,275
occurred in women with IDD. In adjusted regression analyses, women with IDD
compared to those without IDD were significantly more likely to have preterm
birth (OR = 1.46; 95%CI: 1.26-1.69, p < 0.001), low birth weight (OR = 1.61,
95%CI: 1.27-2.05, p < 0.001), and stillbirth (OR = 2.40, 95% CI: 1.70-3.40, p <
0.001). CONCLUSION: This study provides a first examination of the birth outcomes
among women with IDD in the United States using a largest population-based
sample. There are significant differences in birth outcomes between women with
and without IDD. Understanding the causes of these differences and addressing
these causes are critical to improving pregnancy outcomes among women with IDD.
PMID- 28404231
TI - Modulation of sensorimotor circuits during retrieval of negative Autobiographical
Memories: Exploring the impact of personality dimensions.
AB - Autobiographical Memory (AM) retrieval refers to recollection of experienced past
events. Previous Transcranial Magnetic Stimulation (TMS) studies have shown that
presentation of emotional negative stimuli affects human motor cortex
excitability resulting in larger motor evoked potentials (MEPs). Up to date no
TMS studies have been carried out in order to investigate the effect of personal
memories with negative emotional value on corticospinal excitability. In this
study we hypothesized that negative AM retrieval will modulate corticomotor
excitability and sensorimotor integration as determined by TMS neurophysiological
parameters. Furthermore, we investigated whether TMS responses during retrieval
of negative AM are associated with specific personality traits. Twelve healthy
subjects were asked to recall either a negative or a neutral AM across two
different days in a randomized order. During this memory retrieval, the following
TMS parameters were recorded: MEPs; Short- interval intracortical inhibition
(SICI) and Intracortical facilitation (ICF); Short-latency afferent inhibition
(SAI) and Long- latency afferent inhibition (LAI). Personality traits were
assessed by using the Big Five scale. Statistical analysis was performed using
factorial ANOVAs and multiple linear regression models. When compared to
retrieval of neutral AM, recollection of negative AM induced a larger increase in
MEP amplitude, an increase in ICF, and a decrease in SAI. The neuroticism
personality trait was a significant predictor of the MEP amplitude increase
during retrieval of negative AM. Altogether these results indicate that cortical
excitability and sensorimotor integration are selectively modulated by the
valence of AM. These results provide the first TMS evidence that the modulatory
effect of the AM retrieval is associated with specific personality traits.
PMID- 28404232
TI - PCR-based molecular characterization of Blastocystis hominis subtypes in
southwest of Iran.
AB - Blastocystis hominis is the most common intestinal parasite found in humans and
many other hosts. Pathogenicity of Blastocystis sp. remains controversial and it
has been suggested that it may be associated with certain subtypes of organism.
The aim of this study was to evaluate the molecular epidemiology of B. hominis
and its subtype distribution in Ahvaz, southwest of Iran. During 2012-2014, a
total of 481 samples were collected from patients referred to the medical
laboratory centers in Ahvaz for stool examination. Samples were examined by wet
mount, and genomic DNA was extracted from 50 positive samples. PCR was performed
using seven primer pairs targeting the SSU rDNA gene and sequenced. 69 (14.35%)
samples were found to be positive for B. hominis and the subtypes of 50 samples
were identified. Five subtypes (STs) were identified, including: ST1 (22%), ST2
(6%), ST3 (40%), ST4 (2%), and ST5 (8%). 11 (22%) mixed infections were found, of
which 5 were a mixture of ST3/ST4. Mixtures of ST1/ST3 and ST1/ST4 were 3,
respectively. In this study people infected with ST3 showed the most
gastrointestinal symptoms. This is the first study in the population of Ahvaz and
indicates the high prevalence of ST3 in this area. The results suggest a possible
association between this subtype and pathogenic potential of parasite.
PMID- 28404234
TI - Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium
tuberculosis isolates from Iranian patients.
AB - OBJECTIVES: Streptomycin (SM) is one of the most effective drugs for the
treatment of multidrug-resistant (MDR) tuberculosis. However, resistance to SM is
increasingly reported, mainly due to mutations in the rpsL and rrs genes. This
study was designed with the aim of determining the nature of SM resistance and
the type and frequency of rpsL and rrs mutations among SM-resistant Mycobacterium
tuberculosis (MTB) isolates from Iran. METHODS: A total of 100 clinical
monoresistant and MDR MTB isolates were subjected to drug susceptibility testing
(DST) for SM. SM-resistant isolates were genotyped by MIRU-VNTR typing. Fragments
of the rpsL and rrs genes were amplified to investigate the most common
mutations, with subsequent sequence analysis. RESULTS: By DST, 32 isolates (32%)
were identified as SM-resistant, of which 50% (16/32) were MDR. By MIRU-VNTR
typing, the SM-resistant isolates were classified into 20 different MIRU types
and 8 clusters, with Beijing (22%) being the most prevalent genotype. Mutations
in the rrs and rpsL genes were identified in 14 (44%) and 10 (31%) of the 32 SM
resistant isolates, respectively. The most common mutations were at rpsL
nucleotide 128 (AAG->AGG, Lys43Arg), found in 7 SM-resistant isolates (22%) and
nucleotide 263 (A->G, Lys88Arg) in 3 SM-resistant isolates (9%). CONCLUSIONS: The
results suggest an association between rpsL mutation and SM-resistant strains of
Beijing genotype. The existence of SM resistance in 25% of isolates without
mutation in rrs and rpsL suggests the occurrence of further mechanisms associated
with SM resistance in these isolates.
PMID- 28404233
TI - Molecular detection of drug resistance to ofloxacin and kanamycin in
Mycobacterium tuberculosis by using multiplex allele-specific PCR.
AB - Drug resistance in tuberculosis (TB) is the biggest global health challenge as it
hinders the tuberculosis control program and makes the disease more worsen.
Molecular methods interrupt the spread of drug resistance by facilitating the
appropriate anti- tuberculosis therapy at correct time through rapid diagnosis of
multi drug resistant (MDR) and extensively drug resistant tuberculosis (XDR-TB).
In this study we standardized and evaluated the diagnostic utility of multiplex
allele specific PCR (MAS-PCR) targeting gyrA D94G and rrs A1401G mutations for
detection of resistance against two key drugs (ofloxacin and kanamycin) of second
line anti tuberculosis treatment. MAS-PCR assays targeting gyrA D94G and rrs
A1401G for ofloxacin (OFL) and kanamycin (KAN) resistance respectively were
carried out on 150 multidrug resistant isolates of Mycobacterium tuberculosis.
The results were compared with phenotypic drug susceptibility test against
ofloxacin and kanamycin by using proportion method on MGIT 960. Of 150 MDR
isolates 50 were resistant to both ofloxacin and kanamycin, 36 were resistant to
ofloxacin only, 8 were resistant to kanamycin only and 56 were susceptible to
both the drugs. MAS-PCR correctly identified gyrA D94G and rrs A1401G mutations
in phenotypically resistant isolates with a specificity of 100%. The sensitivity
of MAS-PCR was 88.66%, 93.55% and 86% for OFL, KAN and XDR-TB respectively. There
was no mutation detected at gyrA D94G region of 12.86% (11 of 86) OFL resistant
isolates while 6.89% (4 of 58) of KAN resistant isolates did not carry rrs A1401G
substitution. MAS-PCR proves to be a rapid tool for detection of drug resistance
which could also be used as an initial marker for screening of XDR-TB.
PMID- 28404235
TI - Anesthetic management in feline renal transplantation.
AB - OBJECTIVE: To document perioperative and anesthetic management of 30 feline renal
transplant recipients (1996-1998). STUDY DESIGN: Retrospective clinical study.
ANIMALS: Thirty adult cats in end-stage renal failure that underwent heterotopic
renal transplantation. MATERIALS AND METHODS: The medical records were reviewed
from 30 feline heterotopic renal transplant recipients. Cases were included only
if they had been treated for hypertension using a beta-adrenergic antagonist, a
calcium channel blocker or hemodialysis. Data regarding signalment, preoperative
management, surgical technique, type and doses of anesthetics administered,
perioperative hemodynamics and intra- and postoperative complications,
postoperative analgesia, morbidity and early mortality were recorded. Data were
expressed as mean +/- SD. RESULTS: Preanesthetic medication included a
combination of an anticholinergic and an opioid (oxymorphone). Anesthesia
induction was performed mostly with isoflurane and oxygen delivered by mask.
Anesthesia maintenance was primarily achieved with isoflurane in 100% oxygen.
Nitrous oxide was often used as part of the anesthetic technique. The mean
duration of anesthesia was 4.6 hours +/- 27 minutes. The mean renal allograft
ischemic time was 60 minutes. During the anesthetic period, the majority of the
recipient cats received either fresh whole blood (FWB) (N = 25, 83%), cross
matched packed red blood cells (PRBC) (N = 3, 10%) or fresh frozen plasma (FFP)
(N = 2, 7%) combined with a balanced electrolyte solution. Blood products
administered averaged 63 +/- 34 mL and crystalloid 94 +/- 62 mL. The most common
treated intraoperative complications were hypotension (N = 14, 47%), hypothermia
(N = 13, 43%), metabolic acidosis (N = 11, 37%), hypocalcemia (N = 5, 17%),
hypoglycemia (N = 4, 13%), hypertension (N = 2, 7%), bradycardia (N = 1, 3%), and
ventricular premature contractions (N = 1, 3%). All cats received opioid
analgesics postoperatively. Complications observed in the first 24 hours
postoperatively were hypertension (N = 20, 67%), hematuria (N = 14, 47%),
electrolyte disturbances (N = 9, 30%), temperature imbalances (N = 5, 17%),
decreased PCV requiring blood transfusion (N = 5, 17%), decreased perfusion of a
foot associated with external iliac anastomosis technique (N = 5, 17%), seizures
associated with hypertension (N = 3, 10%), uroabdomen (N = 2, 7%), acute graft
rejection (N = 1, 3%) and, corneal ulceration (N = 1, 3%). Survival rates in the
perioperative period were 100, 96.7, and 93.4% intraoperatively, at 24 hours, and
7 days following surgery. CONCLUSION: Successful anesthesia can be performed in
critically ill renal transplant recipients. However, for optimal graft function
and patient survival, normothermia, normovolemia, normotension, and normal acid
base and electrolyte balance should be carefully maintained. Successful
anesthetic management requires understanding of the pathophysiology of end-stage
renal disease and the maintenance of homeostasis during the different stages of
the perioperative period.
PMID- 28404236
TI - The anti-nociceptive and cardiopulmonary effects of extradural fentanyl-xylazine
in sheep.
AB - OBJECTIVE: To compare the anti-nociceptive effects of extradural xylazine,
fentanyl and a xylazine-fentanyl combination in sheep, and to measure the
cardiopulmonary effects of the xylazine-fentanyl combination. STUDY DESIGN:
Prospective, randomized study. ANIMALS: Twenty-five half-merino ewes 2-4 years of
age and body mass 54.2 +/- 1.1 kg. METHODS: Six sheep in group 1 received 0.2 mg
kg-1 xylazine by extradural injection, six in group 2 received fentanyl 1.5 MUg
kg-1 and 13 in group 3 received the combination of both treatments. In all
groups, drugs were mixed with saline (0.15 mL kg-1 before injection). Pulmonary
and carotid arterial catheters were placed in seven sheep of group 3 which were
used to evaluate cardiopulmonary effects. Anti-nociception was determined by the
response to electrical stimulation (40 V for 1.5 milliseconds) of the left flank
and by superficial and deep muscular 'pinpricking' stimulation of the pelvic and
thoracic limbs and thoracolumbar region. RESULTS: Lack of response to electrical
stimulation at the left flank was present in 10 +/- 1.1 minutes (mean +/- SEM)
(group 1) and in 4.5 +/- 0.5 minutes in group 3. The duration of lack of response
to electrical stimulation at the left flank was 96 +/- 6 minutes in group 1 and
315 +/- 6 minutes in group 3. Responses persisted in group 3. Significant
decreases (p < 0.05) in cardiac output 30, 45, 60 and 90 minutes after injection,
and in cardiac work at 30 and 45 minutes were observed in the seven animals of
group 3. Arterial blood pH was lowest at 90 minutes, arterial bicarbonate was
lowest at 60 minutes and values for both arterial and mixed venous base excess
increased significantly at 60 and 90 minutes. There was no significant change
from baseline values in heart rate, mean arterial blood pressure, respiratory
rate, body temperature, systemic vascular resistance, arterial and mixed venous
PO2, PCO2, oxygen saturation, blood oxygen content, haemoglobin concentration,
mixed venous blood bicarbonate and pH. CONCLUSIONS: Fentanyl decreases the onset
time and prolongs the duration of anti-nociception produced by xylazine. The
combination decreases cardiac output but is without significant respiratory
effects. CLINICAL RELEVANCE: Further studies are required to show that surgery is
possible in sheep after extradural xylazine-fentanyl injection.
PMID- 28404237
TI - A new brachial plexus block technique in dogs.
AB - OBJECTIVE: To evaluate the feasibility and efficacy of a new technique of
brachial plexus anesthesia in dogs. STUDY DESIGN: Prospective, experimental
study. ANIMALS: Twelve adult mongrel dogs, six males and six females weighing
14.8 +/- 1.75 kg. METHODS: The animals were sedated with acepromazine 0.05 mg kg
1 and anesthetized with propofol (6 mg kg-1, IV bolus) followed by an infusion of
212 MUg kg-1 minute-1. The brachial plexus block technique was performed
utilizing the brachial artery as an anatomic landmark, the needle was inserted
from the axilla and a nerve stimulator was used to ensure the accuracy of needle
placement. Bupivacaine (0.375% with 5 MUg mL-1 epinephrine) was used at a dose
rate of 4 mg kg-1. Dogs underwent mid-diaphyseal osteotomies of the humerus
followed by intramedullary pin fixation. RESULTS: Onset time to motor and sensory
block were 9.70 +/- 5.52 and 26.20 +/- 8.86 minutes, respectively. Analgesia
lasted for 11.11 +/- 0.47 hours. The block was effective in 91.6% of the animals,
being verified by anesthesia of the whole front limb distal to the shoulder. One
animal became hypotensive after the block and did not undergo the surgery at that
time. In the remaining 10 animals the heart and respiratory rates, blood
pressure, blood gas parameters and plasma bicarbonate concentration did not show
any statistically significant alterations during the surgical procedure.
CONCLUSIONS: This brachial plexus block technique is effective in most cases to
provide surgical analgesia for the front limb distal to the shoulder. CLINICAL
RELEVANCE: Various surgical procedures in the front limb can be performed with a
regional anesthetic technique without the use and concomitant risks of general
anesthesia in dogs. Long-lasting analgesia associated with this technique may
also provide a valuable tool for the management of pain in the forelimb.
PMID- 28404238
TI - Intravenous regional anesthesia in isoflurane anesthetized cats: lidocaine plasma
concentrations and cardiovascular effects.
AB - OBJECTIVE: To determine if intravenous regional anesthesia (IVRA) can be used in
cats without resulting in excessive plasma lidocaine concentrations or adverse
cardiovascular effects. STUDY DESIGN: Prospective, blinded crossover study.
ANIMALS: Seven healthy male young adult cats weighing 3.96 +/- 0.63 kg. METHODS:
At 2.3% end-tidal isoflurane concentration, lidocaine (L) 3 mg kg-1 (1%) or
saline (S) was injected in a distal cephalic venous catheter after application of
two tourniquets to that forelimb which remained in place for 20 minutes. Heart
and respiratory rates, arterial blood pressures and ECG were recorded every 5
minutes during tourniquet application and for 20 minutes following tourniquet
removal. Lidocaine plasma concentrations were measured 5 minutes after injection
and 0.5, 1, 2, 4, 8, 20 and 40 minutes after tourniquet removal. End tidal
isoflurane concentrations were reduced to 1.5-2.0% to elicit a response to toe
pinch (RTP) in the contralateral leg. The study was repeated similarly in the
contralateral leg and RTP was graded for 40 minutes. Response was also tested in
the leg previously injected, the differences between the two scores determined
and those differences compared between the L and S treatments. The data were
analyzed using anova for repeated measures comparing values to baseline.
Significance was set at p < 0.005 using the Bonferroni method for multiple
comparisons. RESULTS: There were no significant differences in physiologic
parameters at either isoflurane concentration. Differences in RTP were
significantly larger in the lidocaine treatment. The highest mean lidocaine
concentrations were measured 0.5 minutes after tourniquet removal after both
injections and were 2.79 +/- 1.05 and 3.10 +/- 1.11 MUg mL-1. The highest
individual plasma concentration was 6.46 MUg mL-1. CONCLUSION: No adverse
hemodynamic effects were evident after IVRA lidocaine in any cat. The lidocaine
dose studied inhibited a RTP until 20 minutes after tourniquet removal. Lidocaine
concentrations varied and were measurable prior to tourniquet removal. CLINICAL
RELEVANCE: IVRA may be a suitable technique for cats undergoing surgery of the
distal limbs.
PMID- 28404239
TI - Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca
fascicularis).
AB - OBJECTIVE: To assess the agreement between three measurements of arterial oxygen
saturation (SpO2, SaO2 and ScO2) in anesthetized cynomolgus monkeys. STUDY
DESIGN: Prospective study. ANIMALS: Eleven mature, male cynomolgus monkeys
(Macaca fasicularis). METHODS: Monkeys were anesthetized with intramuscular
ketamine followed by intravenous propofol. The trachea of each was intubated and
the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V
pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were
taken from an indwelling catheter. Inspired oxygen concentration was varied from
12 to 20%, and 88 paired arterial blood samples and saturation measurements were
taken. Arterial oxygen saturation in the blood samples was measured using a
cooximeter. The saturation was also calculated from the arterial oxygen tension
using the Adair equation. The results were compared using Bland and Altman's
method. RESULTS: The pulse oximeter readings were 2.7% higher than that of the
cooximeter, with a limit of agreement of -3.9 to 9.3%. The pulse oximeter
readings were 1.8% higher than the calculated saturation, with a limit of
agreement of -6.5% to 10.1%. The cooximeter readings were 0.9% lower than the
calculated saturation, with a limit of agreement of -5.6% to 3.8%. CONCLUSIONS:
The agreement between SpO2 and other measurements of arterial oxygen saturation
in this study is typical for this technique. The bias and limits of agreement are
consistent with reports in other species. CLINICAL RELEVANCE: The Nonin 8500 V is
a useful pulse oximeter for clinical use in primates.
PMID- 28404240
TI - Determination of the post mortem interval in skeletal remains by the comparative
use of different physico-chemical methods: Are they reliable as an alternative to
14C?
AB - The determination of the post-mortem interval (PMI) of skeletal remains is a
challenging aspect in the forensic field. Previous studies focused their
attention on different macroscopic and morphological aspects but a thorough and
complete evaluation of the potential of chemical and physical analyses in this
field of research has not been performed. In addition to luminol test and Oxford
histology index (OHI) reported in a recent paper, widely spread and accessible
methods based on physical aspect and chemical characteristics of skeletal remains
have been investigated as potential alternatives to dating by determination of
14C. The investigation was performed on a total of 24 archeological and forensic
bone samples with known PMI, with inductively coupled plasma optical emission
spectrometer (ICP-OES), inductively coupled plasma quadruple mass spectrometry
(ICP-MS), Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X
ray analysis (EDX), powder X-ray diffraction analysis (XRPD) and scanning
electron microscopy (SEM). Finally, the feasibility of such alternative methods
was discussed. Some results such as carbonates/phosphates ratio from FT-IR, the
amounts of organic and inorganic matter by EDX, crystallite sizes with XRPD, and
surface morphology obtained by SEM, showed significant trends along with PMI.
Though, from a chemical point of view cut-off values and gold-standard methods
still present challenges, and rather different techniques together can provide
useful information toward the assessment of the PMI of skeletal remains. It is
however clear that in a hypothetical flowchart those methods may be placed
practically at the same level and a choice should always consider the evaluation
of results by each technique, execution times and a costs/benefits relationship.
PMID- 28404241
TI - Discrete morphological variants of human cervical vertebrae: Exploring pattern of
distribution and biological significance.
AB - Studies on discrete traits of the human cervical vertebrae, appearing at certain
intervals during the last century, posed some questions regarding evolutionary
processes that human cervical spine underwent during phylogenesis. To address
questions of significance of these morphological traits we need first a good
knowledge of the extent of their variation in modern humans. The aim of the
current work was to integrate available data on the occurrence of various non
metric traits in the human cervical spine and search for the pattern of their
distribution on intra- and inter-population levels. The study was based on data
from five osteological samples from North America (Terry and Grant collections)
and Russia (mid 20th c. and 18th c.); and data taken from literature. Traits were
categorized into rare (<3%), low frequency (up to 10%), often encountered (10
30%) and characteristic for modern humans (>50% on average). Several traits
showed mild to strong association with each other indicating interrelation
between various spine characteristics. Of the traits analyzed, the following had
consistent pattern of sex-related variability: complete dorsal ponticle, bifid
spinous processes and cervical ribs; and ancestry-related variability: dorsal
ponticle and bifid spinous processes. Each ancestry group (European, African,
Asian and North American) had its specifics regarding the latter two traits which
might be related to genetic isolation. Most of the traits, however, showed
relatively similar pattern of distribution among various populations, including
the pattern of within-spine variability. This suggests a common intraspecific
pattern and a possible link to some fundamental characteristics of the human
vertebral column.
PMID- 28404242
TI - Propofol anaesthesia for surgery in late gestation pony mares.
AB - OBJECTIVE: To characterize propofol anaesthesia in pregnant ponies. ANIMALS:
Fourteen pony mares, at 256 +/- 49 days gestation, undergoing abdominal surgery
to implant fetal and maternal vascular catheters. MATERIALS AND METHODS: Pre
anaesthetic medication with intravenous (IV) acepromazine (20 ug kg-1),
butorphanol (20 ug kg-1) and detomidine (10 ug kg-1) was given 30 minutes before
induction of anaesthesia with detomidine (10 ug kg-1) and ketamine (2 mg kg-1) IV
Maternal arterial blood pressure was recorded (facial artery) throughout
anaesthesia. Arterial blood gas values and plasma concentrations of glucose,
lactate, cortisol and propofol were measured at 20-minute intervals. Anaesthesia
was maintained with propofol infused initially at 200 ug kg-1 minute-1, and at
130-180 ug kg-1 minute-1 after 60 minutes, ventilation was controlled with oxygen
and nitrous oxide to maintain PaCO2 between 5.0 and 6.0 kPa (37.6 and 45.1 mm Hg)
and PaO2 between 13.3 and 20.0 kPa (100 and 150.4 mm Hg). During anaesthesia
flunixin (1 mg kg-1), procaine penicillin (6 IU) and butorphanol 80 ug kg-1 were
given. Lactated Ringer's solution was infused at 10 mL kg-1 hour-1. Simultaneous
fetal and maternal blood samples were withdrawn at 85-95 minutes. Recovery from
anaesthesia was assisted. RESULTS: Arterial blood gas values remained within
intended limits. Plasma propofol levels stabilized after 20 minutes (range 3.5
9.1 ug kg-1); disposition estimates were clearance 6.13 +/- 1.51 L minute-1 (mean
+/- SD) and volume of distribution 117.1 +/- 38.9 L (mean +/- SD). Plasma
cortisol increased from 193 +/- 43 nmol L-1 before anaesthesia to 421 +/- 96 nmol
L-1 60 minutes after anaesthesia. Surgical conditions were excellent. Fetal
umbilical venous pH, PO2 and PCO2 were 7.35 +/- 0.04, 6.5 +/- 0.5 kPa (49 +/- 4
mm Hg) and 6.9 +/- 0.5 kPa (52 +/- 4 mm Hg); fetal arterial pH, PO2 and PCO2 were
7.29 +/- 0.06, 3.3 +/- 0.8 kPa (25 +/- 6 mm Hg) and 8.7 +/- 0.9 kPa (65 +/- 7 mm
Hg), respectively. Recovery to standing occurred at 46 +/- 17 minutes, and was
generally smooth. Ponies regained normal behaviour patterns immediately.
CONCLUSIONS AND CLINICAL RELEVANCE: Propofol anaesthesia was smooth with
satisfactory cardiovascular function in both mare and fetus; we believe this to
be a suitable anaesthetic technique for pregnant ponies.
PMID- 28404243
TI - Pharmacokinetics and selected behavioral responses to butorphanol and its
metabolites in goats following intravenous and intramuscular administration.
AB - OBJECTIVE: To evaluate disposition of a single dose of butorphanol in goats after
intravenous (IV) and intramuscular (IM) administration and to relate behavioral
changes after butorphanol administration with plasma concentrations. DESIGN:
Randomized experimental study. ANIMALS: Six healthy 3-year-old neutered goats
(one male and five female) weighing 46.5 +/- 10.5 kg (mean +/- D). METHODS: Goats
were given IV and IM butorphanol (0.1 mg kg-1) using a randomized cross-over
design with a 1-week interval between treatments. Heparinized blood samples were
collected at fixed intervals for subsequent determination of plasma butorphanol
concentrations using an enzyme linked immunosorbent assay (ELISA).
Pharmacokinetic values (volume of distribution at steady state [VdSS], systemic
clearance [ClTB], extrapolated peak plasma concentration [C0] or estimated peak
plasma concentration [CMAX], time to estimated peak plasma concentration [TMAX],
distribution and elimination half-lives [t1/2], and bioavailability) were
calculated. Behavior was subjectively scored. A two-tailed paired t-test was used
to compare the elimination half-lives after IV and IM administration. Behavioral
scores are reported as median (range). A Friedman Rank Sums test adjusted for
ties was used to analyze the behavioral scores. A logit model was used to
determine the effect of time and concentration on behavior. A value of p < 0.05
was considered significant. RESULTS: Volume of distribution at steady state after
IV administration of butorphanol was 1.27 +/- 0.73 L kg-1, and ClTB was 0.0096 +/
0.0024 L kg-1 minute-1. Extrapolated C0 of butorphanol after IV administration
was 146.5 +/- 49.8 ng mL-1. Estimated CMAX after IM administration of butorphanol
was 54.98 +/- 14.60 ng mL-1, and TMAX was 16.2 +/- 5.2 minutes; bioavailability
was 82 +/- 41%. Elimination half-life of butorphanol was 1.87 +/- 1.49 and 2.75
+/- 1.93 hours for IV and IM administration, respectively. Goats became
hyperactive after butorphanol administration within the first 5 minutes after
administration. Behavioral scores for goats were significantly different from
baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM
administration. Both time and plasma butorphanol concentration were predictors of
behavior. Behavioral scores of all goats had returned to baseline by 120 minutes
after IV administration and by 240 minutes after IM administration. Conclusions
and Clinical Relevance The dose of butorphanol (0.1 mg kg-1, IV or IM) being
used clinically to treat postoperative pain in goats has an elimination half-life
of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited
after IV and IM administration of butorphanol. Clinical trials to validate the
efficacy of butorphanol as an analgesic in goats are needed.
PMID- 28404244
TI - Evaluation of auditory evoked potentials to predict depth of anaesthesia during
fentanyl/fluanisone-midazolam anaesthesia in rats.
AB - OBJECTIVES: To assess a method for monitoring depth of anaesthesia using
components of middle latency auditory evoked potential (AEP) waveforms during
anaesthesia with fentanyl/fluanisone and midazolam. STUDY DESIGN: Prospective
observational study. ANIMALS: Five female Wistar rats weighing between 210 and
250 g. METHODS: Implanted electrodes were used to record AEPs in animals
receiving five doses of anaesthetic. Recordings were made at 5 minutes post
injection (deep anaesthesia; no pedal withdrawal response, PWR) and then at 25
minutes (light anaesthesia; strong PWR). Responses showed five characteristic
peaks occurring at 11, 14, 23, 42 and 68 ms that were measured for latency of
occurrence and peak amplitude. RESULTS: Auditory evoked potential peaks P14, N23
and P42 were increased significantly in latency with successive anaesthetic
injections [avg. F(1,4) = 12.53, p < 0.001; avg. F(1,4) = 10.6, p < 0.001; avg.
F(1,4) = 3.9, p = 0.02, respectively]. Peak N23 showed a significant reduction in
latency during the 20 minute recovery period following both the first and second
anaesthetic injections (t(3) = 7.52, p = 0.005; t(4) = 5.17, p = 0.007,
respectively). Peak P42 occurred significantly earlier 20 minutes following the
second anaesthetic injection (t(4) = 4.75, p = 0.009). The mean overall depth of
anaesthesia assessed using PWR scores was significantly correlated with the mean
latency of peak N23, such that as the strength of PWR increased, N23 occurred
significantly earlier (r = -0.99, p = 0.01). The amplitude difference between
peaks N23 and P42 increased after the second and third drug administrations [avg.
F(1,4) = 10.65, p = 0.031 and avg. F(1,4) = 11.24, p = 0.028, respectively].
CONCLUSION: The characteristics of these peaks, and in particular latency of peak
N23, may provide a useful tool for assessing depth of anaesthesia produced by
this, and possibly other anaesthetic agents.
PMID- 28404245
TI - Low-volume resuscitation with a haemoglobin-based oxygen carrier Hemoglobin
glutamer-200 (bovine) in canine hypovolaemia.
PMID- 28404246
TI - Effects of the haemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine)
on intestinal perfusion and oxygenation in a canine hypovolaemia model.
PMID- 28404247
TI - Pharmacokinetics of intramuscular medetomidine in domestic sheep.
PMID- 28404248
TI - Buprenorphine disposition after buccal administration in cats: preliminary
observations.
PMID- 28404249
TI - Comparison of analgesia and perioperative problems associated with the
preoperative use of ketoprofen and nimesulide in dogs.
PMID- 28404250
TI - Clinical use of atracurium in horses undergoing ophthalmic surgery.
PMID- 28404251
TI - Pitfalls in using modern gas analysers for monitoring closed-system anaesthesia.
PMID- 28404252
TI - Comparison of intramuscular medetomidine for preanaesthetic medication in sheep
undergoing orthopaedic surgery.
PMID- 28404253
TI - Acepromazine modulates cell differentiation: in vitro experiments on monocytes
stimulated by Chlamydia pneumoniae toxins.
PMID- 28404254
TI - The effect of ketamine infusions on the minimum alveolar concentration of
isoflurane in cats.
PMID- 28404255
TI - Comparison of three different medetomidine/ketamine combinations in NMRI mice.
PMID- 28404256
TI - Comparison of the anaesthesia combinations racemic-ketamine/medetomidine and S
Ketamine/medetomidine in syrian golden hamsters (mesocricetus auratus).
PMID- 28404257
TI - Polymerized bovine hemoglobin (Oxyglobin Solution) administration in two river
otters (Lutra canadensis).
AB - Polymerized bovine hemoglobin (Oxyglobin Solution(r)) was successfully
administered to two river otters (Lutra canadensis) that required general
anesthesia and surgery for trap-related injuries. In both animals, blood oxygen
content was maintained at presurgical levels despite a 47-70% decrease in their
hematocrit. Otter 1 received a dose of 19 mL kg-1, given at a rate of 29 mL kg-1
h-1. Otter 2 received a dose of 20 mL kg-1, given at a rate of 5 mL kg-1 h-1. For
many of the uncommon species, there are limited resources in the form of blood
products to treat anemia, blood loss or hypovolemia. Successful use of
polymerized bovine hemoglobin in these two otters suggests that it is useful for
acute treatment of anemia and blood loss in such species.
PMID- 28404258
TI - Continuous infusion of propofol in dogs premedicated with methotrimeprazine.
AB - OBJECTIVE: To evaluate the cardiopulmonary and clinical effects of three
different infusion rates of propofol in dogs premedicated with methotrimeprazine.
STUDY DESIGN: Randomized experimental trial. ANIMALS: Ten healthy adult mixed
breed male and female dogs, weighing from 14 to 20 kg. METHODS: Dogs were
premedicated with methotrimeprazine [1 mg kg-1 intravenously (IV)] followed by
induction of anesthesia with 4.5 mg kg-1 of propofol IV and maintenance with
propofol for 60 minutes as follows: T1, 0.2 mg kg-1 minute-1; T2, 0.3 mg kg
1minute-1; and T3, 0.4 mg kg-1minute-1. Heart rate (HR), respiratory rate (RR),
mean arterial pressure (MAP), end-tidal CO2 (PETCO2), arterial hemoglobin O2
saturation, arterial blood gases, and pedal and cutaneous reflexes were measured
before and 5, 10, 20, 30, 45 and 60 minutes after the beginning of the propofol
infusion. Statistical analysis was performed using an anova. RESULTS: Heart rate
increased during anesthesia in all cases and arterial blood pressure decreased
only in dogs in the T3 category. Respiratory depression was proportional to the
infusion rate of propofol. Muscle relaxation was satisfactory, but analgesia was
inadequate in the three treatments. CONCLUSIONS: The infusion of 0.2-0.4 mg kg-1
minute-1 of propofol produced a dose-dependent respiratory depression. The
presence of a pedal withdrawal reflex and marked cardiovascular responses to this
noxious stimulus suggests that anesthesia may not be of sufficient depth for
surgery to be carried out. CLINICAL RELEVANCE: Although several studies have been
performed using propofol in animals, few studies have investigated the
cardiopulmonary and analgesic effects with different doses. The determination of
an adequate propofol infusion rate is necessary for the routine use of this
intravenous anesthetic for the maintenance of anesthesia during major surgical
procedures in dogs.
PMID- 28404259
TI - Delayed dyspnoea in pigs possibly associated with endotracheal intubation.
PMID- 28404263
TI - The cardiopulmonary effects of romifidine in dogs with and without prior or
concurrent administration of glycopyrrolate.
AB - OBJECTIVE: To determine the electrocardiographic and cardiopulmonary effects of
romifidine with and without prior or concurrent administration of glycopyrrolate.
STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six (three male,
three female) cross-bred dogs weighing 23 +/- 2.4 kg. METHODS: Baseline
cardiopulmonary measurements were obtained in conscious dogs and one of five
treatments was administered. Glycopyrrolate (G) 0.01 mg kg-1, or saline (S) 0.5
mL, were administered IM as premedication (Gp or Sp), or G was administered
concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40
MUg kg-1; T2, Gp + RO (40 MUg kg-1); T3, Sp + RO 120 MUg kg-1; T4, Gp + RO (120
MUg kg-1); T5, Sp + Gc + RO (120 MUg kg-1). Romifidine or RO + Gc was
administered subcutaneously 20 minutes after premedication (time 0), and further
measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main
treatment effect was evaluated using two-way anova for repeated measures,
followed by one-way anova and a post-hoc least squares difference test with a
modified Bonferroni correction (p < 0.02). A Student's t-test was used to compare
the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05).
RESULTS: Both low- and high-dose RO (T1, T3) significantly decreased heart rate
(HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and
increased arterial blood pressure (SAP), systemic vascular resistance (SVR),
pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High
dose RO produced greater increases in SVR and SAP measurements. Neither dose of
RO produced an alteration in blood gas values or the alveolar to arterial oxygen
gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes
between T1/T2 and T3/T4. Increases in SAP were dose related with significant
differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were
highest in animals receiving Gp or Gc. High-dose RO groups (T3, T4) had higher
values for SVR than low-dose RO groups (T1, T2), unrelated to G administration.
There was an increase in PAOP in all treatments. The oxygen extraction ratio was
increased with all treatments: larger increases were observed in T1, T3 and T4
compared with only minimal changes in T2. Concurrent G administration was
associated with an increased frequency of high-grade second-degree
atrioventricular heart block with variable conduction at 10 and 20 minutes.
CONCLUSIONS: Romifidine produced effects consistent with other selective alpha2
adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially
offset the decrease in CI associated with RO administration. Glycopyrrolate
premedication produced an initial tachycardia and added to the increase in SAP
associated with RO. Concurrent G administration was associated with a higher
frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO
sedation did not alter blood gas values. CLINICAL RELEVANCE: It appears likely
that G administration prior to or concurrent with RO produces an increase in
myocardial workload and oxygen demand suggesting that this combination should not
be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen
extraction ratio with T2 suggests that G may be beneficial with lower doses of
RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is
not advised.
PMID- 28404264
TI - Anaesthesia with ketamine/medetomidine in the rabbit: influence of route of
administration and the effect of combination with butorphanol.
AB - OBJECTIVE: To compare the characteristics of anaesthesia induced with
ketamine/medetomidine administered by the subcutaneous and intramuscular routes
and to assess the effects of the addition of butorphanol to this combination.
STUDY DESIGN: Prospective randomised study. ANIMALS: Six female New Zealand White
rabbits. METHODS: Rabbits were given one of four combinations of ketamine and
medetomidine (K/M) either subcutaneously (SC) or intramuscularly (IM) on four
successive occasions with a 7-day interval between treatments. The dose
combinations were; 15/0.25 mg kg-1 SC; 15/0.25 mg kg-1 IM; 15/0.5 mg kg-1 SC, and
15/0.25 mg kg-1 together with 0.4 mg kg-1 butorphanol (K/M/B) SC. The effects of
anaesthesia on arterial blood gas values and cardiovascular variables were
recorded at predetermined time points. Toe and ear pinch reflexes were judged to
determine the duration of surgical anaesthesia. Loss of the righting reflex was
used to measure the duration of sleep time. Analyses used repeated measures
analysis of variance. RESULTS: All groups lost the righting reflex and ear pinch
response. Three animals in the groups that received K/M alone lost their toe
pinch reflex, whereas four lost this reflex when given K/M/B. Time of onset of
loss of the righting, toe and ear pinch reflexes did not differ significantly
among the groups. The higher dose combination of medetomidine with ketamine and
the combination of K/M/B produced a greater duration of loss of the ear pinch
response than the lower dose of K/M administered by either route. No significant
differences were found among the groups in the duration of loss of the toe pinch
reflex. All animals developed a moderate bradycardia (mean heart rate <166 beats
minute-1) and moderate hypoxaemia (mean PaO2 < 6.0 kPa). Animals given
butorphanol showed the greatest reduction in respiratory rate (31 +/- 13 breaths
minute-1, p < 0.05) but this was not reflected in any significant differences in
arterial PCO2, PO2 or pH among the groups. CONCLUSIONS: Administration of K/M by
the SC route produced equivalent effects in comparison to intramuscular
administration. The addition of butorphanol increased the duration of
anaesthesia, but produced a slight increase in the degree of respiratory
depression. All dose rates resulted in hypoxaemia so oxygen should be
administered when these combinations are used in rabbits. CLINICAL RELEVANCE:
Subcutaneous administration is both technically simpler and may cause less
discomfort to the animal than IM injection, and so is preferred. The combination
of K/M with butorphanol has relatively minor effects on the depth and duration of
anaesthesia, so offers little advantage to the use of K/M alone.
PMID- 28404265
TI - Anaesthesia in horses using halothane and intravenous ketamine-guaiphenesin: a
clinical study.
AB - OBJECTIVE: The aim of this study was to define and evaluate a combined inhalation
intravenous anaesthetic protocol for use in equine anaesthesia. STUDY DESIGN:
Prospective, randomized clinical trial. ANIMALS: Twenty-eight horses (body mass
522 +/- 82; 330-700 kg [mean +/- SD; range]) with a mean age of 6 +/- 4 years
(range: 2-18 years) presented to the university hospital for various surgical
procedures requiring general anaesthesia. MATERIALS AND METHODS: Animals were
randomly allocated to one of two treatment groups. Anaesthesia was maintained in
14 horses with halothane alone (H group). The mean end-tidal halothane
concentration was 1.24%. In the second group (n = 14) anaesthesia was maintained
with both halothane (end-tidal concentration 0.61%) and a continuous infusion of
a ketamine-guaiphenesin mixture (HKG group). The two techniques were compared in
terms of qualitative differences and cardiopulmonary effects. RESULTS: The
stability of anaesthesia was significantly greater in group HKG and the need for
dobutamine to maintain blood pressure was significantly less. Recovery times and
quality were acceptable in all cases. There were no significant differences
between the groups. CONCLUSIONS: The infusion of ketamine and guaiphenesin in
horses receiving low inspired concentrations of halothane provides suitable
surgical anaesthesia and lowers the risk of hypotension. CLINICAL RELEVANCE: The
anaesthetic technique described in this study is a useful and practical
alternative to inhalation anaesthesia using halothane alone.
PMID- 28404266
TI - A preliminary investigation comparing pre-operative morphine and buprenorphine
for postoperative analgesia and sedation in cats.
AB - OBJECTIVE: To compare the postoperative analgesic and sedative properties of
buprenorphine and morphine in cats. STUDY DESIGN: Prospective, randomized,
blinded study. ANIMALS: Thirty-two domestic cats undergoing surgery. METHODS:
Cats received pre-anaesthetic medication with acepromazine (0.05 mg kg-1) given
intramuscularly and were randomly allocated to group M and given morphine (0.1 mg
kg-1) intramuscularly (IM) or to group B and given buprenorphine (0.01 mg kg-1)
IM. Anaesthesia was induced with propofol and maintained with halothane in oxygen
and nitrous oxide. Pain and sedation scores using visual analogue scales, and
heart and respiratory rates, were measured immediately before, and 30, 60, 120,
180, 300 and 420 minutes after anaesthesia. RESULTS: Pain scores were
significantly lower at 60, 120 and 180 minutes after anaesthesia in group B.
Group B also had higher heart rates at 30 minutes. There were no other
statistically significant differences between the groups. CLINICAL RELEVANCE:
Buprenorphine (0.01 mg kg-1) appeared to provide better postoperative analgesia
than morphine (0.1 mg kg-1) and may also have a longer duration of action.
PMID- 28404267
TI - A comparison of three combinations of injectable anesthetics in miniature
donkeys.
AB - OBJECTIVE: To compare three combinations of injectable anesthetics in miniature
donkeys for quality of induction, recovery, muscle relaxation, cardiopulmonary
changes during anesthesia and duration of recumbency. Design Prospective,
randomized experimental study. ANIMALS: Six miniature donkeys (< 90 cm in height
at the withers) weighing 92-127 kg were used. MATERIALS AND METHODS: The drug
combinations were: xylazine-butorphanol-ketamine (XBK), xylazine-butorphanol
tiletamine-zolazepam (XBT) and xylazine-propofol (XP). Each miniature donkey was
anesthetized with each combination at 1-week intervals in random order. Heart and
respiratory rates, indirect blood pressure and temperature were measured before
and at 5-minute intervals during recumbency. Arterial blood samples were drawn
for blood-gas analysis before and at 5, 15 and 30 minutes of anesthesia when
samples could be collected. Recumbency time to sternal and time to standing were
recorded and a subjective evaluation of induction, muscle relaxation and recovery
were made. RESULTS: Mean recumbency time +/- SD was 14.7 +/- 9.4, 33.8 +/- 6.3
and 14.6 +/- 1.9 minutes with XBK, XBT and XP, respectively. Mean time to
standing +/- SD was 28.4 +/- 11.3, 43.7 +/- 7.2 and 26.3 +/- 2.9 minutes with
XBK, XBT and XP, respectively. Heart and respiratory rates and blood pressures
varied from baseline but were always within normal ranges. Hemoglobin saturation,
pH and PaO2 tended to be lower with these doses of XBT and XP. CONCLUSIONS AND
CLINICAL RELEVANCE: Overall quality of anesthesia was poor with XBK. At the doses
used this combination did not provide sufficient anesthesia compared with the
combinations of XBT and XP, which appeared to provide acceptable anesthesia of
short duration in miniature donkeys.
PMID- 28404268
TI - Use of a pulsed electromagnetic field for treatment of post-operative pain in
dogs: a pilot study.
AB - OBJECTIVE: To determine if pulsed electromagnetic field (PEMF) therapy reduces
post-operative pain in dogs following ovariohysterectomy, and to evaluate PEMF
interaction with post-operative morphine analgesia. STUDY DESIGN: Randomized
controlled clinical trail. ANIMALS: Sixteen healthy dogs weighing 18 (10-32) kg
[median (range)] and aged 13 (3-36) months. MATERIALS AND METHODS: Anesthesia
consisted of atropine (0.04 mg kg-1, SC), acepromazine (0.02 mg kg-1, SC),
fentanyl (0.01 mg kg-1, SC), thiopental (10-15 mg kg-1, IV) and halothane in
oxygen. Ovariohysterectomies were performed by senior veterinary students. Pain
score (numeric rating scale, 0-28), pulse rate, respiratory rate, indirect mean
arterial pressure (MAP), and body temperature were evaluated prior to anesthetic
premedication, at extubation, 30 minutes after extubation, and then hourly for 6
hours. Following extubation, dogs were randomly divided into four groups: a
control group that received 0.9% NaCl, IV, and no PEMF; a magnet group that
received 0.9% NaCl, IV, and PEMF; a morphine group that received morphine 0.25 mg
kg-1, IV, and no PEMF; and, a magnet/morphine group that received morphine 0.25
mg kg-1, IV, and PEMF. A single observer, blinded to treatment, obtained all
behavioral observations and physiologic data. Data were analyzed using the
Kruskal-Wallis statistical test with a significance of p < 0.05. RESULTS:
Significant differences in MAP (mm Hg) [median (range)] occurred at 300 minutes
[morphine 108 (83-114) and magnet/morphine 90 (83-97) < magnet 135 (113-117)],
and at 360 minutes [magnet/morphine 93 (81-100) < control 127 (111-129) and
magnet 126 (111-129)]. At 30 minutes the total pain score for the magnet/morphine
group [1.5 (0-5)] was significantly less than control [8 (6-13)], but not
different from magnet [5.5 (4-7)] or morphine [4.5 (2-9)]. CONCLUSIONS AND
CLINICAL RELEVANCE: Although no clear benefit was seen in this study, the results
suggest that PEMF may augment morphine analgesia following ovariohysterectomy in
dogs, and that further study of the analgesic effects of PEMF is warranted.
PMID- 28404269
TI - The clinical use of the neuromuscular blocking agent rocuronium in dogs.
AB - OBJECTIVE: The aim of this study was to characterize the onset and duration of
action of the aminosteroid muscle relaxant rocuronium in dogs under clinical
conditions. STUDY DESIGN: Prospective single dose trial. ANIMALS: Twenty-three
dogs aged between 6 months and 12 years, weighing between 5.5 and 61.5 kg
admitted to the University of Liverpool Small Animal Hospital between January and
March 2000, and undergoing elective surgical procedures under general
anaesthesia. MATERIALS AND METHODS: Following induction of general anaesthesia,
neuromuscular function was evaluated using train-of-four (TOF) stimulation. An
initial dose of 0.4 mg kg-1 rocuronium was administered intravenously (IV) and
neuromuscular blockade was monitored by visually assessing the number of
responses (twitches) to TOF stimulation (train-of-four count: TOFC). Incremental
doses of 0.16 mg kg-1 rocuronium were administered as indicated, when at least
two twitches of the TOFC had returned. RESULTS: Rocuronium (0.4 mg kg-1)
abolished all responses to TOF stimulation in all dogs. The mean time to onset of
neuromuscular blockade (complete abolition of all twitches) was 98 +/- 52
seconds. Neuromuscular blockade (absence of all twitches to return of all four)
lasted 32.3 +/- 8.2 minutes. Incremental doses of 0.16 mg kg-1 had a mean
duration of action of 20.8 +/- 4.9 minutes and up to seven increments were shown
to be noncumulative. The effects of rocuronium were readily antagonized with
neostigmine and atropine. Small transient increases in arterial blood pressure,
which occurred in three dogs after the administration of rocuronium, were the
only cardiovascular side-effects observed. CONCLUSIONS: Rocuronium is an
effective nondepolarizing neuromuscular blocking agent in the dog, with a rapid
onset of neuromuscular block after intravenous administration and an intermediate
duration of action. CLINICAL RELEVANCE: Rocuronium produced a neuromuscular block
with similar characteristics to those obtained with vecuronium, thus apparently
offering little advantage over vecuronium. However, its availability in aqueous
solution and a longer shelf-life increases convenience.
PMID- 28404270
TI - Retrospective analysis of detomidine infusion for standing chemical restraint in
51 horses.
AB - OBJECTIVE: To assess the effectiveness of a detomidine infusion technique to
provide standing chemical restraint in the horse. DESIGN: Retrospective study.
ANIMALS: Fifty-one adult horses aged 9.5 +/- 6.9 years (range 1-23 years) and
weighing 575 +/- 290.3 kg. METHODS: Records of horses presented to our clinic
over a 3-year period in which a detomidine infusion was used to provide standing
chemical restraint were reviewed. Information relating to the types of procedure
performed, duration of infusion, drug dosages and adjunct drugs administered was
retrieved. RESULTS: Detomidine was administered as an initial bolus loading dose
(mean +/- SD) of 7.5 +/- 1.87 MUg kg-1. The initial infusion rate was 0.6 MUg kg
1 minute-1, and this was halved every 15 minutes. The duration of the infusion
ranged from 20 to 135 minutes. Twenty horses received additional detomidine or
butorphanol during the procedure. All horses undergoing surgery received local
anesthesia or epidural analgesia in addition to the detomidine infusion. A wide
variety of procedures were performed in these horses. CONCLUSIONS: Detomidine
administered by infusion provides prolonged periods of chemical restraint in
standing horses. Supplemental sedatives or analgesics may be needed in horses
undergoing surgery. CLINICAL RELEVANCE: An effective method that provides
prolonged periods of chemical restraint in standing horses is described. The
infusion alone did not provide sufficient analgesia for surgery and a significant
proportion of animals required supplemental sedatives and analgesics.
PMID- 28404271
TI - Effects of oxymorphone and hydromorphone on isoflurane minimum alveolar
concentration in dogs.
PMID- 28404272
TI - Cardiovascular and subjective evaluations of oxymorphone/diazepam and
hydromorphone/diazepam induction in experimentally induced hypovolemic dogs.
PMID- 28404273
TI - Bispectral index in dogs anesthetized with isoflurane: comparison with
sevoflurane.
PMID- 28404274
TI - Phospholipid-encapsulated bupivacaine and analgesia after onychectomy in cats.
PMID- 28404275
TI - Preliminary evaluation of pain behaviors following neutering in dogs: effect of
acepromazine dose.
PMID- 28404276
TI - Postoperative arterial blood gases in spay/castration dogs: a comparison of
butorphanol versus hydromorphone.
PMID- 28404277
TI - The influence of inhaled anesthetic and body temperature on serum fentanyl
concentrations with transdermally administered fentanyl in anesthetized dogs.
PMID- 28404278
TI - The effect of preoperative oral carprofen on postoperative pain in dogs
undergoing knee surgery.
PMID- 28404279
TI - The analgesic effects of butorphanol and meloxicam after elective
ovariohysterectomy in dogs.
PMID- 28404280
TI - Quantification of dose-dependent respiratory depression in isoflurane
anesthetized horses.
PMID- 28404281
TI - Comparison of the cardiopulmonary effects of isoflurane and sevoflurane in foals.
PMID- 28404282
TI - Comparison of induction and recovery in foals anesthetized with isoflurane or
sevoflurane.
PMID- 28404283
TI - Intracranial and cerebral perfusion pressures in awake versus isoflurane
anesthetized horses.
PMID- 28404284
TI - Anesthesia for laryngoplasty with or without sacculectomy in 85 draft horses:
comparison with 322 Thoroughbreds.
PMID- 28404285
TI - Evaluation of xylazine, butorphanol and propofol for short-term intravenous
anesthesia in horses.
PMID- 28404286
TI - Evaluation of pulse oximeters in horses.
PMID- 28404287
TI - Cardiopulmonary, hematological, serum chemistry and peritoneal fluid alterations
associated with abdominal insufflation with carbon dioxide during standing
laparoscopy in healthy horses sedated with detomidine and butorphanol.
PMID- 28404288
TI - Urinary effects of xylazine and general anesthesia in horses.
PMID- 28404289
TI - Effect of xylazine and detomidine on urine production in horses deprived of food
and water.
PMID- 28404290
TI - Clinical use of atracurium in large animal species.
PMID- 28404291
TI - Airlifting horses by helicopter: sedation requirements.
PMID- 28404292
TI - Epidural administration of tiletamine-zolazepam in horses.
PMID- 28404293
TI - Pharmacokinetics and pharmacodynamics of butorphanol in llamas following
intravenous and intramuscular administration.
PMID- 28404294
TI - Cutaneous analgesic, respiratory and cardiovascular effects, and beta-endorphin
concentration in CSF and plasma of horses after electro-acupuncture.
PMID- 28404295
TI - Comparison of traditional thermal support with the forced-air warmer system in
Hispaniolan Amazon parrots (Amazona ventralis).
PMID- 28404296
TI - The effects of cervical spinal cord injury on the pattern of breathing in the
rat.
PMID- 28404298
TI - Does increasing self-reliant learning in a cardiopulmonary resuscitation
laboratory improve knowledge and confidence acquisition?
PMID- 28404297
TI - Clinical and cardiopulmonary effects of propofol in the spotted bamboo shark
(Chylloscyllium plagiosum).
PMID- 28404300
TI - Cardiovascular effects of sevoflurane in Holstein calves.
AB - OBJECTIVE: The purpose of this study was to determine the cardiovascular effects
of sevoflurane in calves. STUDY DESIGN: Prospective experimental study. ANIMALS:
Six, healthy, 8-12-week-old Holstein calves weighing 80 +/- 4.5 (mean +/- SEM) kg
were studied. METHODS: Anesthesia was induced by face-mask administration of 7%
sevoflurane in O2. Calves tracheae were intubated, placed in right lateral
recumbency, and maintained with 3.7% end-tidal concentration sevoflurane for 30
minutes to allow catheterization of the auricular artery and placement of a Swan
Ganz thermodilution catheter into the pulmonary artery. After instrumentation,
administration of sevoflurane was temporarily discontinued until mean arterial
pressure was > 100 mm Hg. Baseline values were recorded and the vaporizer output
increased to administer 3.7% end-tidal sevoflurane concentration. Ventilation was
controlled to maintain normocapnia. The following were recorded at 5, 10, 15, 30
and 45 minutes after collection of baseline data and expressed as the mean value
(+/- SEM): direct systolic, diastolic, and mean arterial blood pressures; cardiac
output; mean pulmonary arterial pressure; pulmonary arterial occlusion pressure,
heart rate; and pulmonary arterial temperature. Cardiac index and systemic and
pulmonary vascular resistance values were calculated using standard formulae.
Arterial blood gases were analyzed at baseline, and at 15 and 45 minutes.
Differences from baseline values were determined using one-way analysis of
variance for repeated measures with post-hoc differences between mean values
identified using Dunnet's test (p < 0.05). RESULTS: Mean time from beginning
sevoflurane administration to intubation of the trachea was 224 +/- 9 seconds.
The mean end-tidal sevoflurane concentration at baseline was 0.7 (+/- 0.11)%.
Sevoflurane anesthesia was associated with decreased arterial blood pressure at
all sampling times. Mean arterial blood pressure decreased from a baseline value
of 112 +/- 7 mm Hg to a minimum value of 88 +/- 4 mm Hg at 5 minutes. Compared
with baseline, arterial pH was decreased at 15 minutes. Pulmonary arterial blood
temperature was decreased at 15, 30 and 45 minutes. Arterial CO2 tension
increased from a baseline value of 43 +/- 3 to 54 +/- 4 mm Hg (5.7 +/- 0.4 to 7.2
+/- 0.3 kPa) at 15 minutes. Mean pulmonary arterial pressure was increased at 30
and 45 minutes. Pulmonary arterial occlusion pressure increased from a baseline
value of 18 +/- 2 to 23 +/- 2 mm Hg at 45 minutes. There were no significant
changes in other measured variables. All calves recovered from anesthesia
uneventfully. CONCLUSION: We conclude that sevoflurane for induction and
maintenance of anesthesia was effective and reliable in these calves and that
neither hypotension nor decreased cardiac output was a clinical concern. CLINICAL
RELEVANCE: Use of sevoflurane for mask induction and maintenance of anesthesia in
young calves is a suitable alternative to injectable and other inhalant
anesthetics.
PMID- 28404301
TI - Comparison of lidocaine, xylazine, and lidocaine-xylazine for caudal epidural
analgesia in cattle.
AB - OBJECTIVE: To directly compare the time to onset and duration of analgesia
produced by a lidocaine/xylazine combination with that produced by lidocaine and
xylazine administered alone in the caudal epidural space of dairy cattle. Design
Prospective randomized experimental study. ANIMALS: Nine adult (> 4 years of
age) dairy cows (520-613 kg). METHODS: Caudal epidural analgesia was produced in
all cows with 2% lidocaine (0.22 mg kg-1; 5.5 mL 500 kg-1), 10% xylazine (0.05 mg
kg-1 diluted to 5.5 mL 500 kg-1 with sterile water), and 2% lidocaine/10%
xylazine (0.22 mg kg-1/0.05 mg kg-1; total volume of 5.7 mL 500 kg-1), at no
earlier than weekly intervals in a Latin square design. Time to onset, duration
and cranial spread of analgesia were recorded, as were degree of sedation, ataxia
and ptyalism. RESULTS: No significant difference (p > 0.05) was noted for time
(mean +/- SEM) of onset of analgesia between lidocaine (4.8 +/- 1.0 minutes) and
the lidocaine/xylazine combination (5.1 +/- 0.9 minutes) but onset of analgesia
following xylazine was significantly longer (11.7 +/- 1.0 minutes) than either of
the other two treatments. Lidocaine/xylazine (302.8 +/- 11.0 minutes) produced
analgesia of significantly longer duration than that of xylazine (252.9 +/- 18.9
minutes) and both the lidocaine/xylazine combination and xylazine alone produced
analgesia of significantly longer duration than that produced by lidocaine (81.8
+/- 11.8 minutes). In all cattle, xylazine, administered either alone or with
lidocaine, induced mild to moderate sedation and ataxia and cutaneous analgesia
from the coccyx to T13. Mild ataxia was also present in those cattle receiving
lidocaine alone. CONCLUSION: The combination of xylazine and lidocaine produces
analgesia of quicker onset and longer duration than xylazine administered alone
and of longer duration than lidocaine administered alone. CLINICAL RELEVANCE:
Utilizing this combination, long-duration obstetrical and surgical procedures
could commence relatively soon after epidural injection and could be completed
without re-administration of anesthetic agents.
PMID- 28404302
TI - Motor responses to stimulation during isoflurane anaesthesia in pigs.
AB - OBJECTIVE: To investigate motor responses to stimulation during the transition
from 'deep' (burst suppression) to 'light' isoflurane anaesthesia in pigs. STUDY
DESIGN: Prospective, randomized observational study. ANIMALS: Five castrated male
and five female Norwegian landrace pigs, weighing 19-29 kg. MATERIALS AND
METHODS: Anaesthesia was induced with isoflurane and the inspired concentration
gradually increased until a burst suppression electroencephalogram (EEG) was
recorded. End-tidal isoflurane concentration (FE'ISO) was then allowed to
equilibrate for 30 minutes after which the eyelashes, cornea, nasal septum, anus,
interdigital skin fold, periople, tail and claw were stimulated. The motor
response to stimulation at each location was graded from 0 to 5. End-tidal
isoflurane concentration was decreased 0.3% and the areas re-stimulated; this was
repeated three times in each pig. A linear regression analysis using response as
dependent and anaesthetic level as independent variable was performed for each
stimulus in each pig. Using Student's t-statistic a 95% confidence interval for
the mean slope of each stimulus was constructed. RESULTS: No pig responded to
eyelash brushing. The mean slopes for the other stimuli indicated increasing
responses with decreasing FE'ISO. Responses to periople pinching and tail and
claw clamping showed significant increases. No stimuli consistently increased the
magnitude of response in all pigs, and the appearance and absence of a response
was inconsistent between pigs. Motor responses occurred in at least one pig
during isoflurane burst suppression anaesthesia to all stimuli except eyelash
brushing. CONCLUSIONS: All the stimuli investigated may elicit movement responses
during burst suppression anaesthesia with isoflurane except eyelash brushing. No
consistent response pattern between pigs was observed with decreasing isoflurane
concentration. Of the stimuli evaluated, clamping the tail or claw and pinching
the periople appear the most reliable indicators of anaesthetic depth. CLINICAL
RELEVANCE: The absence or presence of single reflexes does not accurately reflect
the degree of isoflurane-induced cortical depression in individual pigs.
PMID- 28404303
TI - Cardiopulmonary effects associated with head-down position in halothane
anesthetized ponies with or without capnoperitoneum.
AB - OBJECTIVE: To compare the cardiopulmonary effects of the head-down position, with
or without capnoperitoneum, in halothane-anesthetized horses. STUDY DESIGN:
Prospective randomized study. ANIMALS: Five ponies (four mares, one stallion;
bodyweight 302 +/- 38.4 kg [mean +/- SD]) were used. METHODS: The ponies were
anesthetized with xylazine, guiafenesin, ketamine, and maintained with
halothane/oxygen and lungs were ventilated to 40 +/- 2 mm Hg (5.3 +/- 0.3 kPa)
end-tidal CO2 tension. After baseline cardiopulmonary measurements, ponies were
kept in horizontal position for 30 minutes, then tilted head-down 30 degrees to
the horizontal position for 60 minutes, and then returned to a horizontal
position for final measurements. Capnoperitoneum (intra-abdominal pressure: 12 mm
Hg [1.6 kPa]) was introduced after baseline cardiopulmonary measurements, until 5
minutes before the final measurements (treatment INS). Ponies in the control
treatment (CON) did not receive capnoperitoneum. Cardiopulmonary data were
collected every 10 minutes following the baseline measurements until recovery.
RESULTS: In the head-down position, in both treatments, significant decreases
were observed in PaO2, and significant increases were observed in PaCO2, right
atrial blood pressure, arterial to end-tidal CO2 gradient, calculated Vd/Vt and
Qs/Qt ratios. During the head-down position, in CON there was decreased cardiac
index, and in INS, there were decreases in arterial plasma pH and increases in
mean systemic arterial and airway pressures. Treatment INS developed ventilation
perfusion mismatch earlier in the study, and had longer recovery times compared
to CON. CONCLUSION: Cardiac index and systemic blood pressure appeared to be
preserved in INS during the head-down position, but ventilation-perfusion
mismatch appeared earlier with head-down position and capnoperitoneum. CLINICAL
RELEVANCE: Healthy ponies tolerate capnoperitoneum at 12 mm Hg (1.6 kPa) intra
abdominal pressure when tilted head down 30 degrees to the horizontal position.
PMID- 28404304
TI - Changes in the EEG in horses during surgery: the effect of an intravenous
infusion of alfentanil.
PMID- 28404305
TI - A laboratory study of horses recovering from desflurane and isoflurane
anaesthesia.
PMID- 28404306
TI - The effects of ventilation on intercranial and cerebral perfusion pressures in
isoflurane-anaesthetized horses.
PMID- 28404307
TI - Suspected malignant hyperthermia in a horse anaesthetized with halothane.
PMID- 28404308
TI - Comparison of romifidine-ketamine-midazolam and romifidine-tiletamine-zolazepam
total intravenous anaesthesia (TIVA) for clinical anaesthesia in horses.
PMID- 28404309
TI - A clinical evaluation of a mini-Lack breathing system in cats: comparison with a
modified Ayre's T-piece.
PMID- 28404310
TI - A prospective clinical trial on the effects of inhaled albuterol on the Pao2 of
hypoxaemic anaesthetized horses.
PMID- 28404311
TI - Correlation of the antinociceptive action and plasma concentration of fentanyl
following intravenous administration in cats.
PMID- 28404312
TI - The effect of lidocaine and ketamine on thermal thresholds in cats.
PMID- 28404313
TI - Onset and duration of the antinociceptive activity of intravenous fentanyl in
cats.
PMID- 28404314
TI - Systemic uptake of buprenorphine after buccal administration in cats.
PMID- 28404315
TI - The use of tiletamine-zolazepam-ketamine-xylazine anesthesia for feral cat
sterilization.
PMID- 28404316
TI - Nitrous oxide does not consistently reduce isoflurane requirement in cats.
PMID- 28404317
TI - Hemodynamic effects of nitrous oxide in isoflurane anesthetized cats.
PMID- 28404318
TI - Evaluation of pulse oximeters in dogs and cats.
PMID- 28404319
TI - Cardiorespiratory effects of intravenous morphine, xylazine and atropine in dogs.
PMID- 28404320
TI - Influence of extrinsic operational parameters on salt diffusion during ultrasound
assisted meat curing.
AB - The present study investigated the effect of geometric parameters of the
ultrasound instrument during meat salting in order to enhance salt diffusion and
salt distribution in pork meat on a lab scale. The effects of probe size (?2.5
and 1.3cm) and of different distances between the transducer and the meat sample
(0.3, 0.5, and 0.8cm) on NaCl diffusion were investigated. Changes in the
moisture content and NaCl gain were used to evaluate salt distribution and
diffusion in the samples, parallel and perpendicular to ultrasound propagation
direction. Results showed that 0.3cm was the most efficient distance between the
probe and the sample to ensure a higher salt diffusion rate. A distance of 0.5cm
was however considered as a trade-off distance to ensure salt diffusion and
maintenance of meat quality parameters. The enhancement of salt diffusion by
ultrasound was observed to decrease with increased horizontal distance from the
probe. This study is of valuable importance for meat processing industries
willing to apply new technologies on a larger scale and with defined operational
standards. The data suggest that the geometric parameters of ultrasound systems
can have strong influence on the efficiency of ultrasonic enhancement of NaCl
uptake in meat and can be a crucial element in determining salt uptake during
meat processing.
PMID- 28404321
TI - County-level racial prejudice and the black-white gap in infant health outcomes.
AB - OBJECTIVE: Black mothers are 60 percent more likely than white mothers to have
preterm births and twice as likely to have a baby with low birth weight. We
examine whether these black-white gaps in birth outcomes are larger in counties
with higher levels of racial prejudice. METHOD: We use data from the restricted
use natality files in the United States, which provide information on birth
weight, gestation, and maternal characteristics for over 31 million births from
2002 to 2012, combined with county-level data measures of both explicit and
implicit racial prejudice from Project Implicit from over a million individuals
who took the Implicit Association Test during this same period. We compare
counties that are one standard deviation above the mean (high prejudice) with
those that are one standard deviation below the mean (low prejudice) in terms of
their average level of racial prejudice. RESULTS: The black-white gap in low
birth weight is 14 percent larger in counties with high implicit racial prejudice
compared to counties with low prejudice. The black-white gap in preterm births is
29 percent larger in the high prejudice counties. The gaps are even larger when
we use explicit measures of racial prejudice with high prejudice counties having
a black-white gap that is 22 percent larger for low birth weight and 36 percent
larger for preterm births. These relationships do not appear to be biased by the
way the prejudice sample is constructed, since the racial gap in birth outcomes
is unrelated to other county-level biases such as those based on gender or sexual
orientation. CONCLUSION: The black-white gap in United States' birth outcomes is
larger in those counties that have the highest levels of racial prejudice. This
is true for both implicit and explicit racial prejudice, though the strength of
the relationship is strongest for explicit racial prejudice.
PMID- 28404322
TI - Postoperative analgesia in dogs receiving epidural morphine and medetomidine.
PMID- 28404323
TI - Effect of acupuncture on electroencephalographic responses to noxious stimuli in
halothane-anesthetized dogs.
PMID- 28404324
TI - Skin burns associated with use of the Quatrode ECG electrode during MRI utilizing
accessory coils.
PMID- 28404325
TI - Disposition of buprenorphine, morphine and meperidine in the cat.
PMID- 28404326
TI - The effect of buprenorphine, morphine and saline on thermal thresholds in cats.
PMID- 28404327
TI - Pharmacokinetics of the transdermal fentanyl patch in a feline ovariohysterectomy
model.
PMID- 28404328
TI - Behavioral changes and pharmacokinetics of butorphanol in goats following
intravenous and intramuscular administration.
PMID- 28404329
TI - The effect of tiletamine-zolazepam on isoflurane minimum alveolar concentration
in goats.
PMID- 28404330
TI - Intraarticular lidocaine and bupivacaine in sheep undergoing stifle arthrotomy.
PMID- 28404331
TI - Plasma colloid osmotic pressure after blood volume repletion with Oxyglobin,
hetastarch, or whole blood in pregnant sheep.
PMID- 28404332
TI - Cardiovascular effects of butorphanol in sevoflurane-anesthetized calves.
PMID- 28404333
TI - Fetal oxygen content is restored with Oxyglobin resuscitation after maternal
hemorrhage.
PMID- 28404334
TI - Effect of breathing a heliox gas mixture on cardiopulmonary function in horses
anesthetized immediately following exercise.
PMID- 28404335
TI - Nitric oxide production in normal, endotoxemic and critically ill colic horses.
PMID- 28404336
TI - Analgesic, hemodynamic and respiratory effects of caudal epidural meperidine HCl
solution in mares.
PMID- 28404337
TI - Effect of an inhaled beta-2 adrenergic receptor agonist on arterial partial
pressure of oxygen in hypoxemic anesthetized horses.
PMID- 28404338
TI - Case-control analysis for determining possible causes of airway complications
during anesthetic recovery in horses.
PMID- 28404339
TI - Evaluation of anesthesia maintained with halothane and epidural xylazine for hind
limb surgery in horses.
PMID- 28404340
TI - Evaluation of anesthetic and cardiorespiratory effects of tiletamine-zolazepam
ketamine-xylazine-butorphanol and medetomidine-butorphanol-ketamine in guinea
pigs.
PMID- 28404341
TI - Cardiopulmonary and anesthetic effects of sevoflurane in the Greater Bush Baby.
PMID- 28404342
TI - Evaluation of oscillometric blood pressure monitoring during immobilization of
free-ranging Baird's tapirs (Tapirus bairdii) in Costa Rica.
PMID- 28404343
TI - Midazolam/butorphanol/ketamine and the clinically effective dose of isoflurane
anesthesia of ostriches (Struthio camelus).
PMID- 28404344
TI - Use of the human patient simulator to teach veterinary medicine students.
PMID- 28404345
TI - Fluid therapy with artificial colloids: complications and controversies.
AB - Objectives To discuss the advantages and disadvantages of colloidal therapy in
veterinary medicine. Databases used MEDLINE (1966-present), Commonwealth
Agricultural Bureau Abstracts (1973-present), personal files.
PMID- 28404346
TI - Analgesic, hemodynamic and respiratory effects of caudal epidurally administered
ropivacaine hydrochloride in mares.
AB - Objective To determine the analgesic, hemodynamic and respiratory effects,
sedation and ataxia in mares of caudal epidural administration of ropivacaine
hydrochloride solution. Study design Prospective, single-dose trial. Animals Ten
healthy mares weighing from 475 to 565 kg. Methods Intravascular catheters and an
epidural needle were placed after infiltration of the skin and subcutaneous
tissues with 2% lidocaine. Ropivacaine (0.5%, 8 or 9 mL) was then injected
epidurally at the fifth sacral or sacrococcygeal vertebrae, respectively.
Analgesia was determined by lack of sensory perception to electrical stimulation
(> 40 milliamps) and absence of response to needle pricks extending from coccyx
to S2 dermatomes. Electrocardiogram, heart and respiratory rates, rectal
temperature, arterial blood pressure, arterial acid-base (pH, standard
bicarbonate and base excess), gas tensions (PO2, PCO2), PCV, oxyhemoglobin and
total solids concentrations, and numerical scores of perineal analgesia, sedation
(head drop), and ataxia (position of pelvic limbs) were determined before and
during a 5-hour testing period. Analysis of variance (anova) with repeated
measures was used to detect significant (p < 0.05) differences of mean values
from baseline. Results Epidurally administered ropivacaine induced variable
analgesia extending bilaterally from coccyx to S2 (three mares), coccyx to S3
(four mares), and coccyx to S4 (three mares), with minimal sedation, ataxia, and
cardiovascular and respiratory disturbances of mares. Perineal analgesia was
attained at 10 +/- 4 minutes and lasted for 196 +/-42 minutes (mean +/- SD). Five
mares demonstrated inadequate perineal analgesia, probably attributable to
deviation of the spinal needle from the midline. They were successfully blocked
with ropivacaine on another occasion. Epidural ropivacaine significantly reduced
repiratory rates of mares and did not change other variables from baseline.
Conclusions and clinical relevance Ropivacaine (0.5%, 8 mL 500 kg-1) can be
administered caudal epidurally to produce prolonged (> 2.5 hours) bilateral
perineal analgesia with minimal sedation, ataxia, and circulatory and respiratory
disturbances in standing mares.
PMID- 28404347
TI - Electrocardiographic and cardiopulmonary effects of intramuscular administration
of glycopyrrolate and romifidine in conscious beagle dogs.
AB - Objective To determine the electrocardiographic and cardiopulmonary effects of IM
administration of romifidine with and without prior administration of
glycopyrrolate in conscious dogs. Study design Prospective randomized study.
Animals Twelve healthy, adult beagles. Materials and methods Dogs were assigned
at random to each of three treatments with glycopyrrolate (six dogs), and to each
of three treatments without glycopyrrolate (six dogs). Baseline data were
recorded, and saline solution or glycopyrrolate (10 ug kg-1) was given IM. After
15 minutes, saline solution (control) or romifidine (20 or 40 ug kg-1) was given
IM. An ECG, heart rate (HR), systemic blood pressures, and respiratory rate (RR)
were recorded before and 2.5, 5, 10, 15, 30, 45, 60, 75, 90, 105 and 120 minutes
after romifidine administration. Rectal temperature (RT), pH, PaCO2, PaO2,
hematocrit and plasma protein were determined before and 15, 30, 60 and 120
minutes after romifidine administration. Data were analyzed using analysis of
variance for repeated measures and Tukey multiple comparison tests. Results
Without glycopyrrolate, HR (beats minute-1) decreased to minimum values (mean +/-
SD) of 52 +/- 7 and 49 +/- 12 (control 89 +/- 20) 45 minutes after administration
of romifidine at doses of 20 and 40 ug kg-1, respectively. Sinus bradycardia (HR
< 60 beats minute-1), which persisted for up to 120 minutes, was observed in five
of six and six of six dogs given romifidine at doses of 20 and 40 ug kg-1,
respectively. With glycopyrrolate, decreases in HR were prevented and mean
arterial pressure (mm Hg) increased to maximum values of 139 +/- 25 and 173 +/-
17 (control 113 +/- 11) 30 minutes after administration of romifidine at doses of
20 and 40 ug kg-1, respectively. With and without glycopyrrolate, RR did not
change appreciably, RT decreased, and pH, PaCO2, PaO2, hematocrit and plasma
protein did not change after administration of romifidine. Conclusions and
clinical relevance In healthy conscious beagles, IM administration of romifidine
at doses of 20 and 40 ug kg-1 causes sinus bradycardia which persists for up to
120 minutes. Administration of glycopyrrolate 15 minutes before administration of
romifidine, prevents sinus bradycardia and induces moderate increases in arterial
pressure.
PMID- 28404348
TI - A comparison of epidural buprenorphine with epidural morphine for postoperative
analgesia following stifle surgery in dogs.
AB - Objective To compare the efficacy of epidural buprenorphine with epidural
morphine for post-operative pain relief in dogs undergoing cranial cruciate
ligament rupture repair. Study design A randomized, double blind clinical trial.
Animals Twenty client-owned dogs with cranial cruciate ligament rupture. Methods
Dogs were randomly assigned to receive either epidural buprenorphine (4 ug kg-1)
or epidural morphine (0.1 mg kg-1) in a total volume of 0.2 mL kg-1. Epidural
injections were performed immediately after induction of anesthesia. End-tidal
halothane and CO2 were recorded every 15 minutes from the time of epidural
administration of drug to extubation. A numerical rating pain score system was
used by a blinded observer to evaluate analgesia beginning at extubation and
continuing at specific intervals for 24 hours after surgery. Heart rate,
respiratory rate, and blood pressure were recorded noninvasively at the same
times. If pain score indicated moderate discomfort, rescue morphine at 1.0 mg kg
1 was administered intramuscularly. Results There were no significant differences
between groups with respect to pain score, heart rate, respiratory rate, indirect
blood pressure, end-tidal halothane or end-tidal CO2 at any time point. Fifty
percent of dogs in the buprenorphine group and 50% of dogs in the morphine group
required rescue analgesic medication. Time of systemic rescue morphine
administration did not differ significantly between the two groups. There were no
clinically observable side-effects from epidural administration of either drug in
any of the dogs of this study. Conclusions Epidural buprenorphine is as effective
as epidural morphine for the relief of postoperative hindlimb orthopedic pain in
dogs. Clinical relevance Buprenorphine appears to be an effective opioid for
epidural use in healthy dogs. Buprenorphine may offer certain advantages over
morphine for epidural use, such as lower abuse potential and, in some clinics,
reduced cost and less wastage of drug.
PMID- 28404349
TI - Echocardiographic evaluation of the cardiac performance in dogs sedated with high
and low dose romifidine with and without glycopyrrolate.
PMID- 28404350
TI - Morphine or lidocaine infusion as a pre-emptive analgesic for intraocular surgery
in dogs.
PMID- 28404351
TI - Lithium chloride dilution as a new method of cardiac output determination in the
dog: effect of lithium chloride dosage on serum lithium concentration.
PMID- 28404352
TI - Comparison of surface and subdermal electrodes for monitoring bispectral index in
anesthetized dogs.
PMID- 28404353
TI - Comparison of isoflurane and sevoflurane chamber induction and recovery in cats.
PMID- 28404354
TI - The systemic and regional hemodynamic effects of dopamine, dobutamine, dopexamine
and 5% dextrose in sevoflurane anesthetized dogs.
PMID- 28404355
TI - Asthma exacerbations among asthmatic children receiving live attenuated versus
inactivated influenza vaccines.
AB - OBJECTIVE: To investigate whether there is a difference in the risk of asthma
exacerbations between children with pre-existing asthma who receive live
attenuated influenza vaccine (LAIV) compared with inactivated influenza vaccine
(IIV). MATERIAL AND METHODS: We identified IIV and LAIV immunizations occurring
between July 1, 2007 and March 31, 2014 among Kaiser Permanente Northern
California members aged 2 to <18years with a history of asthma, and subsequent
asthma exacerbations seen in the inpatient or Emergency Department (ED) setting.
We calculated the ratio of the odds (OR) of an exacerbation being in the risk
interval (1-14days) versus the comparison interval (29-42days) following
immunization, separately for LAIV and IIV, and then examined whether the OR
differed between children receiving LAIV and those receiving IIV ("difference-in
differences"). RESULTS: Among 387,633 immunizations, 85% were IIV and 15% were
LAIV. Children getting LAIV vs. IIV were less likely to have "current or recent,
persistent" asthma (25% vs. 47%), and more likely to have "remote history" of
asthma (47% vs. 25%). Among IIV-vaccinated asthmatic children, the OR of an
inpatient/ED asthma exacerbation was 0.97 (95% CI: 0.82-1.15). Among LAIV
vaccinated asthmatic children the OR was 0.38 (95% CI: 0.17-0.90). In the
difference-in-differences analysis, the odds of asthma exacerbation following
LAIV were less than IIV (Ratio of ORs: 0.40, CI: 0.17-0.95, p value: 0.04).
CONCLUSION: Among children >=2years old with asthma, we found no increased risk
of asthma exacerbation following LAIV or IIV, and a decreased risk following LAIV
compared to IIV.
PMID- 28404356
TI - Physicians' current use and preferences for male HPV vaccine-related patient
education materials.
AB - Understanding physician preferences for educational materials to support male HPV
vaccination is critical to improving vaccine uptake. Pediatric (Peds) and Family
Medicine (FM) physicians in Florida completed a survey from May-August 2014
assessing current use of male-specific HPV vaccination patient education
materials, and preferences for materials to increase HPV vaccination uptake. Peds
and FM responses were compared with chi-squared or nonparametric tests. Most
participants were FM (53.2%), White (66.6%), non-Hispanic (74.1%), and provided
male patients/parents with HPV educational materials (59.1%). More than half
(55.5%) provided a CDC factsheet for parents. Peds were more likely to indicate
they provide educational materials (p<0.0001) than FM. The preferred source was
the CDC (77.8%). Peds preferred using a factsheet as the medium of information
more often than FM (85.6% vs. 68.0%; p<0.0001). When asked about preferences for
targeted materials, 74.8% of providers indicated they would prefer materials
targeted towards patients, 63.2% preferred information targeted towards parents,
and 20.7% indicated they prefer non-targeted materials. Future research should
focus on the development and testing of new HPV vaccine-specific materials and
communication strategies for Peds and FM physicians.
PMID- 28404357
TI - The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic
lupus erythematosus.
AB - OBJECTIVE: This study evaluated the safety and immunogenicity of qHPV vaccine in
SLE. METHODS: Subjects: 34 women ages 19-50years (yrs.) with mild to moderate SLE
& minimally active or inactive SLE received qHPV vaccine at the standard dosing
schedule. EXCLUSION CRITERIA: active SLE disease (SELENA-SLEDAI>2), history of
severe SLE disease, deep venous thrombosis, on >400mg/day of hydroxychloroquine,
on >15mg/day of prednisone, or active infections. Patients were monitored for
adverse events (AE), SLE flare, generation of thrombogenic antibodies and
thrombosis. Antibody (Ab) levels to HPV 6, 11, 16 & 18 were measured by HPV
competitive Luminex Immunoassay and Geometric Mean Titers (GMTs) were calculated
for each HPV type. Seroconversion was assessed for those seronegative at
baseline. RESULTS: The women in the study: African-American (79%), mean
age=38.1years, mean age at diagnosis of SLE=28.6years, 35.3% had a history of
smoking, 91% had 4 or more sexual partners, 50% had a history of sexually
transmitted diseases, and 27.3% used condoms on a regular basis. Vaccine site
reactions (VSRs) occurred in 62%, all mild. Ninety-seven percent experienced at
least 1 non vaccine adverse event (nvAE) with a total of 493 nvAEs in 33
patients, of which 90% were mild and none were related to vaccine or SLE. There
were 9 serious AEs, none were related to vaccine or SLE, all resolved. No patient
experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies.
Seroconversion rate was 100% with mean GMTs comparable to Gardasil(r) package
insert data. CONCLUSION: In this SLE vaccine study, qHPV vaccine was generally
safe, well tolerated, and highly immunogenic. This clinical trial is registered
on Clinical Trials.gov under number, NCT01741012 and was conducted under the FDA
IND BB14113.
PMID- 28404358
TI - Immune response to hepatitis B vaccination among people with inflammatory bowel
diseases: A systematic review and meta-analysis.
AB - INTRODUCTION: The response rate to hepatitis B virus (HBV) vaccination in
patients with inflammatory bowel disease (IBD) is low and varies markedly. We
performed a systematic review and meta-analysis to determine the response rate to
HBV vaccination and identified the factors predictive of an immune response.
METHODS: We searched PubMed, Cochrane Library, and Embase databases, and reviewed
the titles and abstracts of studies on the efficacy of HBV vaccination in IBD
patients performed through July 2016. Anti-HBs levels>10IU/L was considered to be
an effective immune response. The primary outcome measure was the response rate
to HBV vaccination after series completion, and the secondary outcome was
identification of factors at baseline predictive of an immune response. RESULTS:
Thirteen studies including 1688 patients were eligible for inclusion. Based on a
random-effects model, the pooled rate of a response to HBV vaccination among
patients with IBD was 61% (95% confidence interval [CI]: 53-69). Young age (mean
difference [MD]: -5.7; 95% CI: -8.46, -2.95) and vaccination during disease
remission (relative risk [RR]: 1.62; 95% CI: 1.15-2.29) were associated with a
positive response to HBV vaccination. In addition, no immunosuppressive therapy
was predictive of an immune response compared to immunomodulatory (RR: 1.33; 95%
CI: 1.08-1.63) or anti-tumor necrosis factor-alpha (anti-TNF-alpha) (RR: 1.57;
95% CI: 1.19-2.08) therapy. CONCLUSIONS: Based on this meta-analysis, only three
of five IBD patients will show a serological response to HBV vaccination.
Vaccination should be performed at the time of IBD diagnosis, during disease
remission, or before starting immunosuppressive therapy.
PMID- 28404359
TI - Editorial.
PMID- 28404360
TI - The confidential enquiry into perioperative equine fatalities (CEPEF): mortality
results of Phases 1 and 2.
AB - OBJECTIVES: To document the equine perioperative mortality rate and to highlight
any factor associated with an increased risk of death up to 7 days after
anaesthesia. STUDY DESIGN: A prospective observational epidemiological
multicentre study. METHODS: Data were recorded from all equidae undergoing
general anaesthesia in 62 clinics. Power calculations indicated that 45 000 cases
were required to detect the significance of important variables. Details of each
horse, operation, anaesthetic agents and clinic personnel were recorded. Outcome
at 7 days was recorded as: alive, put to sleep (PTS) or dead. Data were analysed
by a standard multilevel logistic regression approach, considering the effects of
clustering at the level of clinic. RESULTS: Data were collected from 41 824 cases
over 6 years. A total of 39 025 (93.3%) were alive on day 7 and 785 were dead
giving an overall death rate of 1.9% (95% CI: 1.8-2.0) and 2014 (4.8%) were PTS.
About 5846 horses undergoing emergency abdominal surgeries ('colics') were
excluded from subsequent analyses. A total of 35 107 'noncolic' horses were alive
at 7 days and 328 dead giving a death rate for noncolics of 0.9% (95% CI: 0.8
1.0). Five hundred and forty-three (1.5%) noncolic horses classified PTS were
excluded from further analyses. There were 109 (33%) deaths from cardiac arrest
or post-operative cardiovascular collapse, with 107 (32%) from fractures and
myopathies. Fracture repair, out of hours surgery, and age below 1 month was
associated with increased risk of dying whereas the use of acepromazine and
intravenous anaesthetic agent maintenance of anaesthesia was associated with
reduced risk. CONCLUSIONS: A number of potential contributors to the high risk of
anaesthetic-related mortality have been identified. Further investigation of the
underlying mechanism for their apparent harmful effects and development of
alternative techniques is merited.
PMID- 28404361
TI - The effects of ephedrine on intramuscular blood flow and other cardiopulmonary
parameters in halothane-anesthetized ponies.
AB - OBJECTIVE: To evaluate the effect of ephedrine on intramuscular blood flow and
hemodynamic parameters during equine anesthesia. STUDY DESIGN: Prospective
experimental study. ANIMALS: Six healthy adult Welsh Mountain ponies (five males,
one female, mean weight: 267 kg, range: 213-347 kg). METHODS: Halothane
anesthetized ponies received an IV bolus of ephedrine (0.1 mg kg-1), followed 30
minutes later by a second IV ephedrine injection (0.2 mg kg-1). Changes in
intramuscular blood flows (IMBF) in upper and lower triceps brachii were measured
by laser Doppler flowmetry. Cardiopulmonary measurements were made at intervals
for 30 minutes following each injection. Results were compared with values from a
control group, similarly anesthetized but given saline in an earlier study.
RESULTS: Ephedrine at either dose increased heart rate, arterial blood pressure
(AP), cardiac index (CI) and intramuscular blood flow (IMBF), the effects on
these parameters being significant and long-lasting following the higher dose.
Systemic vascular resistance remained unchanged, and was significantly lower than
in the control saline group. PaO2 decreased significantly immediately following
the first injection of ephedrine, then remained unchanged for the remainder of
the experiment. PaCO2 increased slowly throughout the anesthetic period. One pony
developed supraventricular premature complexes following the second injection. No
other side effects were seen. CONCLUSION: Ephedrine at dose rates of 0.2 mg kg-1
IV consistently increased in CI, AP, and IMBF in both forelimbs. CLINICAL
RELEVANCE: Ephedrine may be of use to improve AP, CI and IMBF during halothane
anesthesia, although the occurrence of an arrhythmia in one pony is of concern.
PMID- 28404362
TI - The relationship of muscle perfusion and metabolism with cardiovascular variables
before and after detomidine injection during propofol-ketamine anaesthesia in
horses.
AB - OBJECTIVES: To study in horses (1) the relationship between cardiovascular
variables and muscle perfusion during propofol-ketamine anaesthesia, (2) the
physiological effects of a single intravenous (IV) detomidine injection, (3) the
metabolic response of muscle to anaesthesia, and (4) the effects of propofol
ketamine infusion on respiratory function. STUDY DESIGN: Prospective experimental
study. ANIMALS: Seven standardbred trotters, 5-12 years old, 416-581 kg. METHODS:
Anaesthesia was induced with intravenous (IV) guaifenesin and propofol (2 mg kg
1) and maintained with a continuous IV infusion of propofol (0.15 mg kg-1 minute
1) and ketamine (0.05 mg kg-1 minute-1) with horses positioned in left lateral
recumbency. After 1 hour, detomidine (0.01 mg kg-1) was administered IV and 40-50
minutes later anaesthesia was discontinued. Cardiovascular and respiratory
variables (heart rate, cardiac output, systemic and pulmonary artery blood
pressures, respiratory rate, tidal volume, and inspiratory and expiratory O2 and
CO2) and muscle temperature were measured at pre-determined times. Peripheral
perfusion was measured continuously in the gluteal muscles and skin using laser
Doppler flowmetry (LDF). Muscle biopsy samples from the left and right gluteal
muscles were analysed for glycogen, creatine phosphate, creatine, adenine
nucleotides, inosine monophosphate and lactate. Arterial blood was analysed for
PO2, PCO2, pH, oxygen saturation and HCO3. Mixed venous blood was analysed for
PO2, PCO2, pH, oxygen saturation, HCO3, cortisol, lactate, uric acid,
hypoxanthine, xanthine, creatine kinase, creatinine, aspartate aminotransferase,
electrolytes, total protein, haemoglobin, haematocrit and white blood cell count.
RESULTS: Circulatory function was preserved during propofol-ketamine anaesthesia.
Detomidine caused profound hypertension and bradycardia and decreased cardiac
output and muscle perfusion. Ten minutes after detomidine injection muscle
perfusion had recovered to pre-injection levels, although heart rate and cardiac
output had not. No difference in indices of muscle metabolism was found between
dependent and independent muscles. Anaerobic muscle metabolism, indicated by
decreased muscle and creatine phosphate levels was evident after anaesthesia.
CONCLUSION: Muscle perfusion was closely related to cardiac output but not
arterial blood pressure. Total intravenous anaesthesia with propofol-ketamine
deserves further study despite its respiratory depression effects, as the
combination preserves cardiovascular function. Decreases in high-energy phosphate
stores during recovery show that muscle is vulnerable after anaesthesia.
Continued research is required to clarify the course of muscle metabolic events
during recovery.
PMID- 28404363
TI - The pre-emptive effect of epidural ketamine on wound sensitivity in horses tested
by using von Frey filaments.
AB - OBJECTIVE: To evaluate the pre-emptive analgesic effect of pre-incisional
epidural ketamine. STUDY DESIGN: A blinded, randomized experimental study.
ANIMALS: Sixteen mixed breed mares, 7.6 +/- 2.8 years old, weighing 352 +/- 32
kg. METHODS: In a pilot study, an incision was made on one lateral thigh using a
lidocaine block and no further analgesics, and it was verified that the
nociceptive threshold was lower on the incised side than nonincised side (p <=
0.05), and that von Frey filaments evoked a pain response. The 16 animals were
divided into group A (ketamine, n = 9) and B (saline, n = 7). An epidural
catheter was inserted 24 hours before the trials. The thigh was shaved
bilaterally, and the right side was blocked (incised side) using lidocaine.
Twenty-five minutes later, ketamine (A) or saline (B) was administered
epidurally. Five minutes later, a 10-cm skin incision was made on the right side,
and then sutured. Nociceptive threshold was determined with von Frey filaments at
1, 3, and 5 cm around the incision at 15-minute intervals for 2 hours, then at 4,
6, and 8 hours. Behavioral alterations, heart and respiratory rates were
recorded. Nociceptive thresholds from these points were averaged to obtain mean
values at each time, converted to a logarithmic scale, and submitted to a
nonparametric analysis (Mann-Whitney and one-way repeated measures anova test, p
<= 0.05). RESULTS: After 8 hours, the global range score revealed reduced
hyperalgesia (p < 0.01) around the incision in 92% (4.65-4.27) of evaluated
intervals in group A (ketamine). There were no significant changes in behavior,
heart and respiratory rates. CONCLUSIONS: It was concluded that pre-emptive
epidural ketamine reduced post-incisional pain in the horse, and that von Frey
filaments were able to quantify cutaneous sensitivity after tissue damage.
CLINICAL RELEVANCE: Epidural ketamine injection can reduce post-incisional
sensitivity in the horse.
PMID- 28404364
TI - Behavioral responses following eight anesthetic induction protocols in horses.
AB - OBJECTIVE: To compare behavioral characteristics of induction and recovery in
horses anesthetized with eight anesthetic drug protocols. STUDY DESIGN:
Randomized prospective experimental study. ANIMALS: Eight horses, 5.5 +/- 2.4
years (mean +/- SD) of age, and weighing 505 +/- 31 kg. METHODS: After xylazine
pre-medication, each of eight horses was anesthetized on four occasions using one
of eight different anesthetic induction protocols which incorporated various
combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg
kg-1; THIO 6 mg kg-1 + PRO 0.5 mg kg-1; THIO 4 mg kg-1 + PRO 1 mg kg-1; THIO 2 mg
kg-1 + PRO 1.5 mg kg-1; KET 2 mg kg-1; KET 1.5 mg kg-1 + PRO 0.5 mg kg-1; KET 1
mg kg-1 + PRO 1 mg kg-1; KET 0.5 mg kg-1 + PRO 1.5 mg kg-1. Quality of induction
and recovery were scored from 1 (poor) to 5 (excellent), and time taken to
achieve lateral recumbency, first movement, sternal recumbency, and standing were
evaluated. RESULTS: Time taken to achieve lateral recumbency after drug
administration differed significantly (p < 0.0001) among the various
combinations, being shortest in horses receiving THIO-8 (mean +/- SD, 0.5 +/- 0.3
minutes) and longest in horses receiving KET-2 (1.4 +/- 0.2 minutes). The best
scores for induction quality were associated with KET-1.5 + PRO-0.5, and the
worst scores for induction quality were associated with KET-2, although the
difference was not significant. Time to first movement varied significantly among
drug protocols (p = 0.0133), being shortest in horses receiving KET-2 (12.7 +/-
3.6 minutes) and longest in horses receiving THIO-8 (29.9 +/- 1.5 minutes).
Horses receiving THIO-8 made the greatest number of attempts to attain sternal
posture (6.5 +/- 4.7) and to stand (1.6 +/- 0.8). Horses in the THIO-8 treatment
also received the poorest recovery scores (3.3 +/- 1.0 and 3.0 +/- 0.7 for
sternal and standing postures, respectively). The best recovery scores were
associated with combinations comprised mainly of propofol. CONCLUSIONS: Combining
propofol with either ketamine or thiopental modifies behaviors associated with
use of the individual drugs. CLINICAL RELEVANCE: Quality of early anesthesia
recovery in horses may be improved by some combinations of propofol with either
thiopental or ketamine.
PMID- 28404365
TI - Aerosolized salbutamol (albuterol) improves PaO2 in hypoxaemic anaesthetized
horses - a prospective clinical trial in 81 horses.
AB - OBJECTIVE: To compare the arterial pH and blood gas values, heart rate and mean
arterial blood pressure, in hypoxaemic anaesthetized horses, before and after
treatment, with a salbutamol (albuterol) aerosol. ANIMAL POPULATION: Eighty-one
client-owned horses weighing between 114 and 925 kg. Fifty-seven underwent
emergency abdominal surgery and 24 were anaesthetized for elective procedures.
MATERIALS AND METHODS: Pre-anaesthetic medication included xylazine, detomidine,
butorphanol and morphine, alone or in various combinations. Induction of
anaesthesia was achieved with guaifenesin and ketamine, diazepam and ketamine, or
guaifenesin and thiopental. The trachea of all animals was intubated and
anaesthesia maintained with either halothane (33 horses) or isoflurane (48
horses) in oxygen. Heart rate and rhythm were monitored continuously. Arterial
blood pressure was monitored directly, and arterial blood collected for pH and
blood gas analyses. When arterial PaO2 fell below 9.3 kPa (70 mm Hg) and failed
to respond to corrective measures including positive pressure ventilation and
treatment of hypotension (mean arterial blood pressures <70 mm Hg), a salbutamol
aerosol (2 MUg kg-1) was delivered via the endotracheal tube. Twenty minutes
later, a second arterial blood sample was analysed. RESULTS: There were no
significant differences in mean arterial blood pressure, heart rate, arterial pH,
base excess and bicarbonate before and after treatment. Arterial O2 tension
increased significantly from a mean +/- SD of 8.3 +/- 1.7 kPa (62.4 +/- 13.1 mm
Hg) before administration to 15.9 +/- 9.8 kPa (119.4 +/- 57.7 mm Hg) after
treatment. There was a small but significant decrease in PaCO2 from 7.4 +/- 1.5
kPa (55.2 +/- 11.2 mm Hg) to 7.0 +/- 1.3 kPa (52.9 +/- 9.8 mm Hg) between sample
times. No changes in heart rhythm were observed. A high percentage (approximately
70%) of animals sweated following treatment. CONCLUSIONS: Salbutamol administered
at a dose of 2 MUg kg-1 via the endotracheal tube of anaesthetized horses with
PaO2 values less than 9.3 kPa (70 mm Hg) resulted in an almost two-fold increase
in PaO2 values within 20 minutes of treatment. No changes in heart rate or mean
arterial blood pressure were associated with the use of salbutamol in this study.
The improvement in PaO2 may be a result of bronchodilatation and improved
ventilation, increased perfusion secondary to an increase in cardiac output, or a
combination of these two factors. Cardiac output and ventilation-perfusion
distribution were not measured in this study; therefore, the reason for the
increase in PaO2 values cannot be conclusively determined. CLINICAL RELEVANCE:
Administration of a salbutamol aerosol is a simple but effective technique that
can be used to improve PaO2 values in hypoxaemic horses during inhalant
anaesthesia with no apparent detrimental side effects.
PMID- 28404366
TI - Serum concentrations and effects of detomidine delivered orally to horses in
three different mediums.
AB - OBJECTIVE: To compare the effect of orally delivered detomidine on head posture
when administered alone or in combination with two different food items, and to
determine the serum concentrations of detomidine after oral delivery. STUDY
DESIGN: Prospective randomized experimental study. ANIMALS: Fifteen adult grade
mares weighing 328-537 kg. METHODS: The horses were randomly assigned to one of
the three treatment groups (five horses each). The groups were given detomidine
(0.06 mg kg-1): alone; mixed with 3 mL of an apple sauce and gum mixture; or
mixed with 3 mL molasses. Head droop, measured before treatment and at 15, 30,
45, 60, 75, 90, and 105 minutes after treatment, was used to evaluate sedation.
Yohimbine (0.1 mg kg-1 IV) was administered after the 90-minute evaluation. Blood
samples were collected from the detomidine-alone group before treatment and at
15, 30, 45, 60, 75, and 90 minutes after treatment. Sera were analyzed for
detomidine equivalent concentrations by an ELISA. Head droop percentages were
compared using a repeated measures analysis of variance. RESULTS: Significant
mean head droop developed in each treatment group by 30 minutes and persisted
until reversal with yohimbine. After yohimbine administration, head positions
returned to 87-91% of pre-treatment levels. There were no significant differences
among the oral treatment groups at any time. Mean serum detomidine equivalents
increased slowly until 45-minute post-administration, but never exceeded 30 ng mL
1. CONCLUSIONS: Orally administered detomidine results in measurable serum drug
concentrations using any of the delivery mediums investigated, and can be
expected to produce profound head droop in horses approximately 45 minutes after
administration.
PMID- 28404367
TI - Detomidine reduces isoflurane anesthetic requirement (MAC) in horses.
AB - OBJECTIVE: To quantitate the dose- and time-related magnitude of the anesthetic
sparing effect of, and selected physiological responses to detomidine during
isoflurane anesthesia in horses. STUDY DESIGN: Randomized cross-over study.
ANIMALS: Three, healthy, young adult horses weighing 485 +/- 14 kg. METHODS:
Horses were anesthetized on two occasions to determine the minimum alveolar
concentration (MAC) of isoflurane in O2 and then to measure the anesthetic
sparing effect (time-related MAC reduction) following IV detomidine (0.03 and
0.06 mg kg-1). Selected common measures of cardiopulmonary function, blood
glucose and urinary output were also recorded. RESULTS: Isoflurane MAC was 1.44
+/- 0.07% (mean +/- SEM). This was reduced by 42.8 +/- 5.4% and 44.8 +/- 3.0% at
83 +/- 23 and 125 +/- 36 minutes, respectively, following 0.03 and 0.06 mg kg-1,
detomidine. The MAC reduction was detomidine dose- and time-dependent. There was
a tendency for mild cardiovascular and respiratory depression, especially
following the higher detomidine dose. Detomidine increased both blood glucose and
urine flow; the magnitude of these changes was time- and dose-dependent
CONCLUSIONS: Detomidine reduces anesthetic requirement for isoflurane and
increases blood glucose concentration and urine flow in horses. These changes
were dose- and time-related. CLINICAL RELEVANCE: The results imply potent
anesthetic sparing actions by detomidine. The detomidine-related increased urine
flow should be considered in designing anesthetic protocols for individual
horses.
PMID- 28404371
TI - Editorial.
PMID- 28404372
TI - Enantioseparation of novel chiral sulfoxides on chlorinated polysaccharide
stationary phases in supercritical fluid chromatography.
AB - Asymmetric sulfoxides is a particular case of chirality that may be found in
natural as well as synthetic products. Twenty-four original molecules containing
a sulfur atom as a centre of chirality were analyzed in supercritical fluid
chromatography on seven polysaccharide-based chiral stationary phases (CSP) with
carbon dioxide - methanol mobile phases. While all the tested CSP provided
enantioseparation for a large part of the racemates, chlorinated cellulosic
phases proved to be both highly retentive and highly enantioselective towards
these species. Favourable structural features were determined by careful
comparison of the enantioseparation of the probe molecules. Molecular modelling
studies indicate that U-shaped (folded) conformations were most favorable to
achieve high enantioresolution on these CSP, while linear (extended)
conformations were not so clearly discriminated. For a subset of these species
adopting different conformations, a broad range of mobile phase compositions,
ranging from 20 to 100% methanol in carbon dioxide, were investigated. While
retention decreased continuously in this range, enantioseparation varied in a non
monotonous fashion. Abrupt changes in the tendency curves of retention and
selectivity were observed when methanol proportion reaches about 60%, suggesting
that a change in the conformation of the analytes and/or chiral selector is
occurring at this point.
PMID- 28404373
TI - Self-assembly of glutamic acid linked paclitaxel dimers into nanoparticles for
chemotherapy.
AB - In this work, a glutamic acid linked paclitaxel (PTX) dimer (Glu-PTX2) with high
PTX content of 88.9wt% was designed and synthesized. Glu-PTX2 could self-assemble
into nanoparticles (Glu-PTX2 NPs) in aqueous solution to increase the water
solubility of PTX. Glu-PTX2 NPs were characterized by electron microscopy and
dynamic light scattering, exhibiting spherical morphology and favorable
structural stability in aqueous media. Glu-PTX2 NPs could be internalized by
cancer cells as revealed by confocal laser scanning microscopy and exert potent
cytotoxicity. It is envisaged that Glu-PTX2 NPs would be an alternative
formulation for PTX, and such amino acid linked drug dimers could also be applied
to other therapeutic agents.
PMID- 28404376
TI - Watershed spinal cord infarction developing after a hypotensive episode secondary
to massive rectus sheath hematoma.
PMID- 28404375
TI - Synthesis and structure-activity relationship study of pyrazolo[3,4-d]pyrimidines
as tyrosine kinase RET inhibitors.
AB - Three series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and
evaluated as RET kinase inhibitors. Compounds 23a and 23c were identified to show
significant activity both in the biochemical and the BaF3/CCDC6-RET cell assays.
Compound 23c was found to significantly inhibit RET phosphorylation and down
stream signaling in BaF3/CCDC6-RET cells, confirming its potent cellular RET
targeting profile. Different from other RET inhibitors with equal potency against
KDR that associated with severe toxicity, 23c did not show significant KDR
inhibition even at the concentration of 1MUM. These results demonstrated that 23c
is a potent and selective RET inhibitor.
PMID- 28404374
TI - Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by
application of a conformational restriction strategy.
AB - The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases,
especially in the oncology area, has singled it as one of the most explored
therapeutic targets in the last two decades. Many different inhibitor classes
have been developed by the industry and academia with a diverse selectivity
profile within the PI3K family. In the present manuscript we report a further
exploration of our lead PI3K inhibitor ETP-46321 (Martinez Gonzalez et al.,
2012)1 by the application of a conformational restriction strategy. For that
purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine
derivatives as PI3K inhibitors. This new class of compounds had enable the
exploration of the solvent-accessible region within PI3K and resulted in the
identification of molecule 8q with the best selectivity PI3Kalpha/delta isoform
profile in vitro, and promising in vivo PK data.
PMID- 28404380
TI - Evaluation of the side-effects and thermal antinociceptive effects of intravenous
hydromorphone in cats.
PMID- 28404378
TI - Axl molecular targeting counteracts aggressiveness but not platinum-resistance of
ovarian carcinoma cells.
AB - Ovarian carcinoma, the most common gynaecological cancer, is characterized by
high lethality mainly due to late diagnosis and treatment failure. The efficacy
of platinum drug-based therapy in the disease is limited by the occurrence of
drug resistance, a phenomenon often associated with increased metastatic
potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian
carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study
was to examine if Axl inhibition modulates drug resistance and aggressive
features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive
and -resistant cell lines. We found that mRNA and protein levels of Axl were
increased in the platinum-resistant IGROV-1/Pt1 and IGROV-1/OHP cell lines
compared to the parental IGROV-1 cells. IGROV-1/Pt1 cells displayed increased
migratory and invasive capabilities. When Axl was silenced, these cells exhibited
reduced growth and invasive/migratory capabilities compared to control siRNA
transfected cells, associated with decreased p38 and STAT3 phosphorylation. In
keeping with this evidence, pharmacological inhibition of p38 and STAT3 decreased
IGROV-1/Pt1 invasive capability. Molecular inhibition of Axl did not sensitize
IGROV-1/Pt1 cells to cisplatin, but enhanced ErbB3 activation in IGROV-1/Pt1
cells and suppressed the clonogenic capability of various ovarian carcinoma cell
lines. The combination of cisplatin and AZD8931, a small molecule which inhibits
ErbB3, produced a synergistic effect in IGROV-1/Pt1 cells. Thus, Axl targeting
per se reduces invasive capability of drug-resistant cells, but sensitization to
cisplatin requires the concomitant inhibition of additional survival pathways.
PMID- 28404377
TI - H2S-induced S-sulfhydration of lactate dehydrogenase a (LDHA) stimulates cellular
bioenergetics in HCT116 colon cancer cells.
AB - Cystathionine-beta-synthase (CBS) is upregulated and hydrogen sulfide (H2S)
production is increased in colon cancer cells. The functional consequence of this
response is stimulation of cellular bioenergetics and tumor growth and
proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various
colon cancer cells and has been previously implicated in tumor cell bioenergetics
and proliferation. In the present study, we sought to determine the potential
interaction between the H2S pathway and LDH activity in the control of
bioenergetics and proliferation of colon cancer, using the colon cancer line
HCT116. Low concentrations of GYY4137 (a slow-releasing H2S donor) enhanced
mitochondrial function (oxygen consumption, ATP production, and spare respiratory
capacity) and glycolysis in HCT116 cells. SiRNA-mediated transient silencing of
LDHA attenuated the GYY4137-induced stimulation of mitochondrial respiration, but
not of glycolysis. H2S induced the S-sulfhydration of Cys163 in recombinant LDHA,
and stimulated LDHA activity. The H2S-induced stimulation of LDHA activity was
absent in C163A LDHA. As shown in HCT116 cell whole extracts, in addition to LDHA
activation, GYY4137 also stimulated LDHB activity, although to a smaller extent.
Total cellular lactate and pyruvate measurements showed that in HCT116 cells LDHA
catalyzes the conversion of pyruvate to lactate. Total cellular lactate levels
were increased by GYY4137 in wild-type cells (but not in cells with LDHA
silencing). LDHA silencing sensitized HCT116 cells to glucose oxidase (GOx)
induced oxidative stress; this was further exacerbated with GYY4137 treatment.
Treatment with low concentrations of GYY4137 (0.3mM) or GOx (0.01U/ml)
significantly increased the proliferation rate of HCT116 cells; the effect of
GOx, but not the effect of GYY4137 was attenuated by LDHA silencing. The current
report points to the involvement of LDHA in the stimulatory effect of H2S on
mitochondrial respiration in colon cancer cells and characterizes some of the
functional interactions between LDHA and H2S-stimulated bioenergetics under
resting conditions, as well as during oxidative stress.
PMID- 28404379
TI - The effect of four anesthetic protocols on the spleen in dogs.
PMID- 28404381
TI - Comparison of two injectable anesthetic regimes in feral cats at a large-volume
spay clinic.
PMID- 28404382
TI - Comparison between S(+) ketamine-diazepam and S(+) ketamine-midazolam on
anesthetic induction and recovery in dogs.
PMID- 28404383
TI - Cardiovascular effects of propofol alone and in combination with ketamine for
total intravenous anesthesia in healthy cats.
PMID- 28404384
TI - Echocardiographic evaluation of dogs receiving 1:1 thiopental/propofol in a
clinical setting.
PMID- 28404385
TI - Comparison of sevoflurane and isoflurane anesthetic index in unpremedicated dogs.
PMID- 28404386
TI - Effect of pre-medication on gastroduodenoscopy in isoflurane-anesthetized cats.
PMID- 28404387
TI - Effect of intravenous lidocaine on isoflurane MAC in dogs.
PMID- 28404388
TI - Measurement of cardiac output by transesophageal Doppler ultrasonography in
anesthetized dogs: comparison with thermodilution.
PMID- 28404389
TI - Hemodynamic effects of sevoflurane in spontaneously breathing cats.
PMID- 28404390
TI - Inhalant anesthetic requirement in cats is animal-dependent.
PMID- 28404391
TI - Validation of the MAC technique in dogs and rabbits.
PMID- 28404392
TI - Quantitative characteristics of anesthetic induction with and recovery from
isoflurane and sevoflurane in cats.
PMID- 28404393
TI - Effect of 0.1, 0.2, 0.4, and 0.8 mg kg-1 of intravenous butorphanol on thermal
antinociception in cats.
PMID- 28404394
TI - Thermal antinociceptive pharmacodynamics of 0.1 mg kg-1 hydromorphone
administered intramuscularly in cats and effect of concurrent butorphanol
administration.
PMID- 28404395
TI - Comparison of the pharmacokinetics and thermal antinociceptive pharmacodynamics
of 20 MUg kg-1 buprenorphine administered sublingually or intravenously in cats.
PMID- 28404396
TI - Effect of low-dose ketamine on thermal thresholds in cats.
PMID- 28404397
TI - Analgesic effect of pre-operative etodolac and butorphanol administration in dogs
undergoing ovariohysterectomy.
PMID- 28404398
TI - Evaluation of intraperitoneal and subcutaneous lidocaine and bupivacaine for
analgesia following ovariohysterectomy in the dog.
PMID- 28404399
TI - Comparison of carprofen and butorphanol as post-surgical analgesics in cats.
PMID- 28404400
TI - Comparison of opioid and alpha-2 adrenergic receptor location and density in the
horse and dog using radioligand binding.
PMID- 28404401
TI - Cardiorespiratory effects of a cardioselective muscarinic antagonist in
anesthetized horses.
PMID- 28404402
TI - The evaluation of analgesia provided by epidural ketamine in dogs with chemically
induced synovitis.
PMID- 28404403
TI - An ethogram of post-anesthetic recovery behaviors in horses: comparison of pre-
and post-anesthetic behaviors.
PMID- 28404404
TI - Endotracheal intubation in horses: a study of two cuff inflation pressures,
correlation with liquid aspiration, and tracheal wall damage.
PMID- 28404405
TI - Cardiopulmonary effects of diazepam/ketamine/isoflurane or
xylazine/ketamine/isoflurane in foals undergoing abdominal surgery.
PMID- 28404406
TI - A comparison of anesthetic risk factors and outcomes in light and draft horses.
PMID- 28404407
TI - A comparison of two intramuscular doses of xylazine-ketamine combination and
tolazoline reversal in llamas.
PMID- 28404408
TI - Assessment of the Hemocue-b for measuring hemoglobin in horse blood.
PMID- 28404409
TI - Liposome-encapsulated oxymorphone prevents hyperalgesia for 7 days in a rat model
of neuropathic pain.
PMID- 28404410
TI - Urethane anesthesia in adult female rats: preliminary observations.
PMID- 28404411
TI - Liposome-encapsulated oxymorphone provides prolonged relief of post-surgical
visceral pain in rats.
PMID- 28404412
TI - Use of a laryngeal mask airway in rabbits during isoflurane anesthesia.
PMID- 28404413
TI - Effectiveness of passive gas-scavenging canisters attached to isoflurane
anesthesia systems under standard-use conditions in a laboratory animal facility.
PMID- 28404414
TI - Web-based, interactive simulation of an anesthesia machine.
PMID- 28404415
TI - The effect of medetomidine and its antagonism with atipamezole on stress-related
hormones, metabolites, physiologic responses, sedation, and analgesia in goats.
PMID- 28404416
TI - We should be designing better experiments.
PMID- 28404417
TI - The role of the reviewer.
PMID- 28404418
TI - Perineal analgesic actions of epidural clonidine in cattle.
AB - OBJECTIVE: To determine the analgesic, sedative, motor, cardiac and respiratory
effects of epidural clonidine in cattle. STUDY DESIGN: Prospective randomized
study. ANIMAL POPULATION: Six healthy male cattle weighing between 236 and 365
kg. METHODS: To investigate the effect of epidural clonidine, the animals
received 2 and 3 MUg kg-1 of clonidine diluted to 8 mL with 0.9% saline. Two
treatments were utilized as controls. The animals from the first control
treatment received 2% lidocaine (0.4 mg kg-1) and those from the second received
an equal volume of 0.9% saline. Each animal received each treatment in random
order. Evaluations of analgesia, sedation, muscle relaxation, heart rate,
respiratory rate and rectal temperature were obtained at 0 (basal), 2, 5, 10, 15
and 30 minutes after epidural injection, and then at 30-minute intervals until
loss of analgesia occurred. All the animals received a standard noxious stimulus
consisting of needle insertion into the skin and deep muscle; a 4-point scale was
used to score the response. A second scale was used to score sedation and a third
for muscle relaxation. RESULTS: Both doses of clonidine were effective in
producing analgesia of the tail, perineum, and upper hindlimb. Complete analgesia
was present before (mean +/- SE = 9 +/- 4 vs. 19 +/- 9 minutes) and lasted longer
(311 +/- 33 vs. 192 +/- 27 minutes) for the 3 MUg kg-1versus the 2 MUg kg-1 dose,
respectively. A dose-dependent sedative effect of clonidine was also observed,
with a peak effect between 60 and 180 minutes. No effects on heart or respiratory
rates were observed with either dose of clonidine. CONCLUSIONS: Epidural
administration of 2 and 3 MUg kg-1 of clonidine in cattle in this study provided
bilateral perineal analgesia/anesthesia with a dose-dependent onset and duration
of action. CLINICAL RELEVANCE: Further studies are required to determine whether
the analgesia is sufficient for surgery.
PMID- 28404419
TI - Hormonal, metabolic and physiological effects of laparoscopic surgery using a
detomidine-buprenorphine combination in standing horses.
AB - OBJECTIVE: To assess the hormonal, metabolic and physiological effects of
laparascopic surgery performed under a sedative analgesic combination of
detomidine and buprenorphine in standing horses. STUDY DESIGN: Prospective study.
ANIMALS: Eight healthy adult Dutch Warmblood horses and five healthy adult ponies
undergoing laparoscopy were studied. Five healthy adult horses not undergoing
laparoscopy were used as a control group. METHODS: The sedative effect of an
initial detomidine and buprenorphine injection was maintained using a continuous
infusion of detomidine alone. The heart and respiratory rate, arterial blood pH
and arterial oxygen and carbon dioxide tensions were monitored, while blood
samples were taken for the measurement of glucose, lactate, cortisol, insulin and
nonesterified fatty acids (NEFA). The same variables were monitored in a control
group of horses which were sedated, but which did not undergo surgery. At the end
of the sedation period the effects of detomidine were antagonized using
atipamezole. RESULTS: The protocol provided suitable conditions for standing
laparoscopy in horses. Laparoscopy induced obvious metabolic and endocrine
responses which, with the exception of NEFA values, were not significantly
different from changes found in the control group. While atipamezole did not
produce detectable adverse effects, it is possible that anatagonism may not be
essential. CONCLUSIONS: The technique described reliably produces adequate
sedation and analgesia for laparoscopic procedures. The level of
sedation/analgesia was controlled by decreasing or increasing the infusion rate.
Antagonism of the effects of detomidine may not be necessary in all cases.
PMID- 28404420
TI - The cardiopulmonary effects of severe blood loss in anesthetized horses.
AB - OBJECTIVE: To characterize the acute cardiopulmonary effects of severe hemorrhage
in anesthetized horses. STUDY DESIGN: Prospective experimental study. ANIMALS:
Three geldings and six mares, aged 14.4 +/- 2.7 years, weighing 486 +/- 41 kg
(range: 425-550 kg). METHODS: Horses were anesthetized using xylazine,
guaifenesin, ketamine and halothane or isoflurane. Cardiovascular variables,
hematocrit, total solids, capillary refill time (CRT) and color of mucous
membranes were measured as blood was collected from the carotid artery into
sterile plastic bags. Arterial blood gas analysis was also performed. RESULTS:
The average amount of blood collected from these horses was (mean +/- SD) 53 +/-
4.8 mL kg-1 bodyweight (range: 23-32 kg) over 39 +/- 4 minutes. Hematocrit
decreased from 38 +/- 3 to 32 +/- 2% after induction of anesthesia and did not
change significantly over the period of blood loss. Total solids decreased
significantly after induction of anesthesia, and over the period of blood loss.
Systolic, mean, diastolic and pulse pressures decreased as blood was lost. Heart
rate did not change significantly. Capillary refill time increased from 1.6 +/-
0.4 seconds to 4.8 +/- 1.3 seconds as blood loss increased. Mucous membrane color
deteriorated progressively. Arterial PO2 decreased significantly over the period
of blood loss. CONCLUSIONS: Hematocrit and heart rate do not change significantly
during acute severe hemorrhage in the anesthetized horse. Arterial blood
pressure, pulse pressure and PaO2 decrease as blood loss increases. Changes in
mucous membrane color and CRT also occur as blood loss increases. CLINICAL
RELEVANCE: During severe hemorrhage in the inhalant-anesthetized horse, both
heart rate and hematocrit remain unchanged. Blood pressure decreases and changes
in arterial PO2 correlate most strongly with volume of blood lost.
PMID- 28404421
TI - Antinociceptive effect of intrathecally applied alpha2 agonists (xylazine and
detomidine) in sheep and the response to atipamezole.
PMID- 28404422
TI - Do common anaesthetic protocols influence cerebral oxygenation?
PMID- 28404423
TI - Short-term anaesthesia in piglets using a liquid injection, rebreathing, inhaler
device.
PMID- 28404424
TI - The effect of low dose rocuronium bromide on eyeball position, muscle relaxation,
and ventilation in dogs.
PMID- 28404425
TI - A comparison of two different methods for dead space measurements in ventilated
dogs.
PMID- 28404426
TI - Influences of carprofen and the experience of the surgeon on post-castration pain
in lambs and young sheep.
PMID- 28404427
TI - Adaptation of thermal threshold analgesiometry for NSAIDs in cats: effects of
ketoprofen.
PMID- 28404428
TI - The isoflurane sparing effect of a medetomidine constant rate infusion in horses.
PMID- 28404429
TI - Clinical use of mivacurium in the cat.
PMID- 28404430
TI - Ketoprofen reduces the minimum alveolar concentration (MAC) in dogs anaesthetized
with isoflurane and fentanyl.
PMID- 28404431
TI - Blood pressure and electrocardiographic effects of acepromazine in anaesthetized
horses.
PMID- 28404432
TI - Comparative study of the effects of acepromazine and structurally related
compounds on the TNF-a release by monocytes stimulated by Chlamydia pneumoniae.
PMID- 28404433
TI - The effects of pre-anesthetic administration of xylazine on the cardiovascular
responses to dobutamine in halothane anaesthetized horses.
PMID- 28404434
TI - Use of the Anemon Index to evaluate the quality of analgesia during fentanyl and
sevoflurane anaesthesia in pigs.
PMID- 28404435
TI - Preliminary evaluation of subjective scoring systems for assessment of
postoperative pain in horses.
PMID- 28404436
TI - A comparison of the haemodynamic effects of epidurally administered medetomidine
and xylazine in dogs.
PMID- 28404437
TI - Comparative cardiovascular, analgesic, and sedative effects of medetomidine,
medetomidine-hydromorphone, and medetomidine-butorphanol in dogs.
PMID- 28404438
TI - Effects of acepromazine on the incidence of vomiting associated with opioid
administration in dogs.
PMID- 28404440
TI - Proceedings of the Association of Veterinary Anaesthetists Spring Meeting,
Dublin, Ireland, 30-31 May 2002.
PMID- 28404439
TI - Haemodynamic changes during labour: continuous minimally invasive monitoring in
20 healthy parturients.
AB - BACKGROUND: There are few studies on maternal haemodynamic changes during labour.
None have used continuous cardiac output monitoring during all labour stages. In
this observational study, we monitored haemodynamic variables continuously during
the entire course of labour in healthy parturients. METHODS: Continuous
haemodynamic monitoring with the LiDCOplus technique was performed in 20 healthy
parturients during spontaneous labour, vaginal delivery and for 15minutes
postpartum. Cardiac output, stroke volume, heart rate, systemic vascular
resistance, and systolic arterial pressure were measured longitudinally at
baseline (periods between/without contractions) and during contractions in early
and late stage 1, stage 2, during delivery, and postpartum, and were analysed
with marginal linear models. RESULTS: Twenty parturients were included. In early
stage 1, baseline cardiac output was 6.3L/min (95% CI 5.7 to 6.9). Baseline
values were similar across both labour stages and postpartum for all haemodynamic
variables. During stage 2 contractions, cardiac output decreased by 32%, stroke
volume decreased by 44%, heart rate increased by 52%, systemic vascular
resistance increased by 88%, and systolic arterial pressure increased by 36%
compared to baseline. During stage 1 contractions, haemodynamic changes were less
profound and less uniform than during stage 2. CONCLUSION: Progression of labour
had no major effect on haemodynamic baseline values. Haemodynamic stress during
contractions was substantial in both labour stages, yet most pronounced during
the second stage of labour. The absence of an increase in stroke volume and
cardiac output postpartum questions the common belief in an immediate rise in
cardiac output after delivery due to autotransfusion from the contracted uterus.
PMID- 28404441
TI - Intravenous anaesthesia using detomidine, ketamine and guaiphenesin for
laparotomy in pregnant pony mares.
AB - Objective To characterize intravenous anaesthesia with detomidine, ketamine and
guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260-320 days
gestation undergoing abdominal surgery to implant fetal and maternal vascular
catheters. Materials and methods Pre-anaesthetic medication with intravenous (IV)
acepromazine (30 ug kg-1), butorphanol (20 ug kg-1) and detomidine (10 ug kg-1)
preceded induction of anaesthesia with detomidine (10 ug kg-1) and ketamine (2 mg
kg-1) IV Maternal arterial blood pressure was measured directly throughout
anaesthesia and arterial blood samples were taken at 20-minute intervals for
measurement of blood gases and plasma concentrations of cortisol, glucose and
lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL
1), ketamine (4 mg mL-1) and guaiphenesin (100 mg mL-1) (DKG) for 140 minutes.
Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted
to maintain PaCO2 between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO2 was kept
close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and
maternal blood samples were withdrawn at 90 minutes. Recovery quality was
assessed. Results DKG was infused at 0.67 +/- 0.17 mL kg-1 hour-1 for 1 hour then
reduced, reaching 0.28 +/- 0.14 mL kg-1 hour-1 at 140 minutes. Arterial blood gas
values and pH remained within intended limits. During anaesthesia there was no
change in heart rate, but arterial blood pressure decreased by 10%. Plasma
glucose and lactate increased (10-fold and 2-fold, respectively) and cortisol
decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO2 and PCO2 were
7.34 +/- 0.06, 5.8 +/- 0.9 kPa (44 +/- 7 mm Hg) and 6.7 +/- 0.8 kPa (50 +/- 6 mm
Hg); and fetal arterial pH, PO2 and PCO2 were 7.29 +/- 0.06, 4.0 +/- 0.7 kPa (30
+/- 5 mm Hg) and 7.8 +/- 1.7 kPa (59 +/- 13 mm Hg), respectively. Surgical
conditions were good but four ponies required a single additional dose of
ketamine. Ponies took 60 +/- 28 minutes to stand and recovery was good.
Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while
cardiovascular function in mare and fetus was well preserved. This indicates that
DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae.
PMID- 28404442
TI - Electroencephalographic and cardiovascular indicators of nociception during
isoflurane anaesthesia in pigs.
AB - Objective To evaluate electroencephalographic indices, invasive arterial blood
pressure and pulse rate as indicators of nociception during isoflurane
anaesthesia in pigs. Animals Ten Norwegian Landrace pigs, five castrated males
and five females, weighing between 19 and 29 kg. Materials and methods The pigs
were anaesthetized with isoflurane and prepared for the measurement of heart rate
(HR), mean arterial pressure (MAP) and the electroencephalogram (EEG). The
inspired isoflurane concentration (Fi'ISO) was then adjusted until the
suppression ratio (SR) exceeded 20%, after which the corresponding end-expired
concentration (Fe'ISO) was maintained for 30 minutes. The effects of noxious
stimuli, consisting of pinching (nasal septum, interdigital web, anus, periople)
and clamping (tail, claw) on spectral edge frequency 95%, median frequency,
alpha/delta ratio, beta/delta ratio, theta/delta ratio, total power, suppression
ratio, MAP and HR were recorded. Fe'ISO was then decreased by 0.3% and maintained
for 30 minutes after which noxious stimulation was re-applied. This was repeated
twice with Fe'ISO reductions of 0.3% being applied each time. Changes in measured
variables before and after noxious stimulation were then compared at each of four
levels of anaesthesia. Results Noxious stimulation caused significant MAP
increases at the lowest two levels for Fe'ISO. There were no significant changes
in the other variables examined. Conclusion Of the variables examined, mean
arterial blood pressure is the most sensitive indicator of nociception in
isoflurane-anaesthetized pigs. Clinical relevance When evaluating nociception
under isoflurane anaesthesia in pigs mean arterial blood pressure should be
monitored when surgery is performed.
PMID- 28404443
TI - Endocrine, haematological and metabolic responses to sevoflurane anaesthesia in
lambs.
AB - Objective To compare the magnitude and duration of the peri-operative
haematological, endocrine and metabolic effects of surgery performed under
sevoflurane anaesthesia. Study Design Prospective randomized study. Animals Ten,
55-day-old lambs of both sexes, mean weight 20.8 +/- 0.3 kg (range 18.5-23.6 kg).
Methods Animals were randomly allocated to two equal groups. All were
anaesthetized with sevoflurane for 3 hours. Surgery (end-to-end anastomosis of
the right carotid artery and right jugular vein) was performed in animals of
Group 1 only. The electrocardiogram, pulse oximetry, cardiac output and
noninvasive arterial blood pressure (NIBP) were monitored. Venous blood samples
(5 mL) were taken 30 minutes before induction of anaesthesia (T = 0) and 1 (T1),
24 (T2), 48 hours (T3) and 7 days (T4) after anaesthesia in order to measure
plasma cortisol, ACTH, insulin, cyclic adenosine monophosphate (cAMP), glucose,
protein concentrations and haematological variables. Results Sevoflurane
decreased NIBP (minimum mean value: 64 +/- 3 mm Hg) in both groups. Plasma
cortisol and ACTH concentration increased in Group 1 (maximum mean values:
cortisol: 136.2 nmol L-1, ACTH: 54.5 pmol L-1) and Group 2 (maximum mean values:
cortisol: 128.7 nmol L-1, ACTH: 44.0 pmol L-1). Cyclic AMP increased only in
Group 1 (9.3 nmol) 1 hour after anaesthesia. Neutrophilia, lymphopaenia and a
decreased PCV were observed in both groups 1 hour after anaesthesia. Plasma
protein and glucose concentrations did not change. Conclusions Increased ACTH and
cortisol concentrations recorded 1 hour after anaesthesia suggest that
sevoflurane induces a stress response in lambs. Clinical relevance The study did
not identify the mechanism by which sevoflurane induces a stress response
although hypotension is implicated.
PMID- 28404444
TI - Distribution of new methylene blue injected into the dorsolumbar epidural space
in cows.
AB - Objective To describe the effect of injection volume and anatomy on the spread of
new methylene blue (NMB) injected into the epidural space between the first and
second lumbar vertebrae in cows. Study Design Prospective experimental study.
Sample Population Thirteen nonpregnant cows. Methods Cows were randomly assigned
to two groups. Group 1 received 5 mL and Group 2 received 10 mL of 0.12% NMB in
0.9% saline. The injection was made into the first interlumbar epidural space
using a dorsal approach. The extent of cranial and caudal migration of the dye,
as manifested by the staining of the epidural fat and dura mater, was measured.
Results Mean +/- SEM number (range) of stained vertebrae was significantly
greater in the 10-mL group than in the 5-mL group, 4.4 +/- 0.6 (T11 to L5) and
3.0 +/- 0.2 (T12 to L3), respectively (p < 0.05). Linear regression analysis
showed that the volume was significantly correlated with the number of stained
vertebrae (R2 = 0.42, p = 0.016). In the dorsal and lateral aspect of the spinal
cord, there were two types of distribution of NMB along the surface of the
epidural fat: between the periosteum and epidural fat; and between the epidural
fat and dura mater. Migration under the spinal cord occurred along the two
longitudinal epidural veins. Conclusions and Clinical Relevance The larger the
volume of solution injected into the first interlumbar epidural space, the
greater the spread. Intrinsic anatomic factors, such as characteristics of
epidural fat and veins, influence the epidural spread of injected solution and,
consequently, epidural analgesia.
PMID- 28404446
TI - The use of the nondepolarizing neuromuscular blocking drug cis-atracurium in
dogs.
AB - Objective This clinical trial attempted to evaluate the potency, onset and
duration of action of cis-atracurium in dogs. Animals Twenty dogs aged between 1
and 15 years and weighing between 15 and 85 kg admitted for a variety of
elective, surgical procedures under general anaesthesia. Materials and methods
Following induction of general anaesthesia, the effects of an intravenous loading
dose of cis-atracurium (0.1 mg kg-1) were evaluated by counting visual responses
to train of four (TOF) nerve stimulation. Incremental doses of 0.02 or 0.04 mg kg
1 cis-atracurium were administered when the first of four responses to TOF
stimulation was present. Results An initial dose of 0.1 mg kg-1 eliminated all
four TOF responses in 18 out of 20 dogs. The same dose, repeated 10 minutes later
in two animals in which blockade was incomplete, abolished all responses. In dogs
receiving 0.1 mg kg-1 cis-atracurium neuromuscular blockade lasted 27.2 +/- 9.3
minutes. Up to six incremental doses were given in individual animals;
incremental doses appeared to be noncumulative. No untoward side-effects were
observed with the use of this drug. There was considerable variation between
individuals in response to cis-atracurium. Conclusions Cis-atracurium is an
effective neuromuscular blocking agent in the dog, although its potency varies.
Clinical Relevance Further studies are required to determine whether observed
differences in potency are related to age, breed or sex. Cis-atracurium may prove
useful in dogs with impaired renal and or hepatic function.
PMID- 28404445
TI - Comparison of two insulin protocols for diabetic dogs undergoing cataract
surgery.
AB - Objective To evaluate the effectiveness of two insulin doses to maintain an
acceptable range of blood glucose concentrations (70-200 mg dL-1) in the peri
operative period in diabetic dogs. Animals Twenty-four diabetic dogs with a
median weight of 20.6 kg and a median age of 8 years old. Methods The dogs were
randomly assigned to receive either 25 or 100% of their normal insulin dose
subcutaneously on the morning of surgery. The anesthetic and feeding protocols
were standardized. On the day before surgery, venous blood was collected for
measurement of beta-hydroxybutyrate, cholesterol, glucose, glycosylated
hemoglobin, hematocrit, total plasma protein and urea nitrogen. On the day of
surgery, blood glucose concentrations were measured prior to anesthesia, prior to
the start of surgery, 1 and 2 hours after beginning of surgery, 1 hour after
extubation, at 16 : 00 hours and at 20 : 00 hours. beta-hydroxybutyrate
concentrations were measured at 20 : 00 hours that day. At 08 : 00 hours the
following day, beta-hydroxybutyrate and glucose concentrations were measured. The
significance of differences between groups was tested with Wilcoxon's two-tailed
rank-sum test, Chi-square test and Fisher's exact test. Results There were no
differences in insulin treatments, clinical signs, concurrent diseases and most
clinicopathological parameters between the two groups of dogs at entry to the
study. The 25% dose group had blood glucose values of 296 (102-601) mg dL-1 at 16
: 00 hours and 429 (97-595) mg dL-1 at 20 : 00 hours on the day of surgery. The
100% insulin dose group had lower corresponding values of 130 (55-375) mg dL-1 (p
= 0.04) and 185 (51-440) mg dL-1 (p = 0.004). No other differences (p < 0.05)
were detected between the two groups. Conclusions The administration of a full
dose of insulin is only marginally advantageous for reducing glucose to normal
(70-120 mg dL-1) after anesthesia but neither dose consistently induced glycemic
values in an acceptable range (70-200 mg dL-1) or normoketonemia. Clinical
relevance Blood glucose should be measured immediately before anesthesia and
periodically throughout the peri-operative period in all diabetic dogs because
presurgical subcutaneous administration of 25 or 100% of the normal insulin dose
resulted in unpredictable blood glucose concentrations.
PMID- 28404447
TI - The Komesaroff anaesthetic machine for delivering sevoflurane to dogs.
AB - Objective To quantify the vapour output of the Komesaroff machine when using
sevoflurane and to determine its performance for inducing and maintaining
sevoflurane anaesthesia in dogs. Study design Prospective experimental study.
Animals Six clinically normal beagles, aged 3-6 years and weighing 20 +/- 1.65 kg
(mean +/- SEM). Methods The first study was performed using five Komesaroff
vaporizers to measure the sevoflurane concentration delivered at each tap setting
(I to IV) at 5, 10, 15, 20, 25, 30 and 35 minutes. For this study a ventilator
was connected to the Komesaroff machine and set to deliver a tidal volume of 250
mL at 10 cycles minute-1; oxygen flow was 100 mL minute-1. A three-litre
reservoir bag was attached to the Y-piece connector to act as a lung model. In
the second study anaesthesia was induced in dogs with sevoflurane delivered by
face-mask mask and carried in 2 L minute-1 100% oxygen and with the vaporizer set
at the fully open position. The quality and speed of induction were recorded.
After orotracheal intubation, anaesthesia was maintained for 60 minutes with
sevoflurane using an oxygen flow of 100 mL minute-1. The dogs were allowed to
breathe spontaneously. The respiratory rate (RR), heart rate (HR), oesophageal
temperature, systolic (SAP) mean (MAP) and diastolic (DAP) arterial pressure, end
tidal CO2 concentration (Fe'CO2) end-tidal (Fe'SEVO) and peak-inspired (FiSEVO)
percentages of sevoflurane, and vaporizer tap setting were recorded every 5
minutes during anaesthesia. Results The delivery of sevoflurane was constant for
each vaporizer setting. The mean output of sevoflurane was 0.44 +/- 0.01% for
setting I, 2.59 +/- 0.18% for setting II, 3.28 +/- 0.22% for setting III and 3.1
+/- 0.5% for setting IV. In the second study, the mean induction time was 7.72 +/
0.60 minutes and the quality of the induction was good in all dogs. The mean
vaporizer tap setting for the maintenance of anaesthesia was 3.48 +/- 0.12 and
the mean values for Fe'SEVO and FiSEVO were 2.42 +/- 0.04% and 2.87 +/- 0.06%,
respectively. The pedal withdrawal reflex persisted throughout anaesthesia.
Conclusions It proved impossible to produce surgical anaesthesia with sevoflurane
delivered by the Komesaroff machine despite the highest possible sevoflurane
concentration being delivered. Clinical relevance Sevoflurane delivered from the
Komesaroff machine cannot be relied upon to maintain surgical anaesthesia in
spontaneously breathing dogs.
PMID- 28404448
TI - Chemical restraint by medetomidine and medetomidine-midazolam and its reversal by
atipamezole in Japanese macaques (Macaca fuscata).
AB - Objective To evaluate the sedative effects of medetomidine, and a medetomidine
midazolam combination, in Japanese macaques and the antagonism of medetomidine
midazolam with atipamezole. Study design Prospective randomized study. Animals
Thirteen healthy Japanese macaques between 3 and 21 years old and weighing
between 4.3 and 15.1 kg. Methods Medetomidine (120 ug kg-1) alone or a
medetomidine (30 ug kg-1) plus midazolam (0.3 mg kg-1) mixture were injected
intramuscularly in the hind limb of 12 animals (n = 6 for each group) and their
effects, particularly behavioural changes, response to external stimuli, sedative
onset time, time to lateral recumbency and time in lateral recumbency, were
monitored for 120 minutes. Another group (n = 7) were given medetomidine
midazolam and injected 30 minutes later with atipamezole (120 ug kg-1).
Behavioural changes and responses to external stimuli were assessed as before.
Results Animals given medetomidine became sedated but could be aroused by
external stimuli. Despite the lower (25%) dose of medetomidine involved, the
effects of medetomidine-midazolam were more marked. Macaques given this
combination became sedated in 4 +/- 2 minutes (mean +/- SD) and remained
unresponsive to external stimuli for at least 60 minutes. Five out of six
macaques became laterally recumbent for 74 +/- 37 minutes. Intramuscular
atipamezole effectively reversed sedation, shortening the arousal and total
recovery time. The recovery from sedation was rapid and smooth, being completed
19 +/- 11 minutes after antagonism. Conclusions The medetomidine-midazolam
combination described provided useful chemical restraint and may prove useful in
macaques undergoing some experimental, diagnostic or therapeutic procedures. The
use of atipamezole as an antagonist increases the value of this technique in
macaques.
PMID- 28404449
TI - Dr Gordon Jackson Rees mb, chb, frca, frcp, frcpch.
PMID- 28404450
TI - Does lying in the recovery position increase the likelihood of not delivering
cardiopulmonary resuscitation?
AB - BACKGROUND: Resuscitation guidelines endorse unconscious and normally breathing
out-of-hospital victims to be placed in the recovery position to secure airway
patency, but recently a debate has been opened as to whether the recovery
position threatens the cardiac arrest victim's safety assessment and delays the
start of cardiopulmonary resuscitation. AIM: To compare the assessment of the
victim's breathing arrest while placed in the recovery position versus
maintaining an open airway with the continuous head tilt and chin lift technique
to know whether the recovery position delays the cardiac arrest victim's
assessment and the start of cardiopulmonary resuscitation. METHODS: Basic life
support-trained university students were randomly divided into two groups: one
received a standardized cardiopulmonary resuscitation refresher course including
the recovery position and the other received a modified cardiopulmonary
resuscitation course using continuous head tilt and chin lift for unconscious and
spontaneously breathing patients. A human simulation test to evaluate the
victim's breathing assessment was performed a week later. RESULT: In total, 59
participants with an average age of 21.9 years were included. Only 14 of 27
(51.85%) students in the recovery position group versus 23 of 28 (82.14%) in the
head tilt and chin lift group p=0.006 (OR 6.571) detected breathing arrest within
2min. CONCLUSION: The recovery position hindered breathing assessment, delayed
breathing arrest identification and the initiation of cardiac compressions, and
significantly increased the likelihood of not starting cardiopulmonary
resuscitation when compared to the results shown when the continuous head tilt
and chin lift technique was used.
PMID- 28404451
TI - Anandamide and 2-AG are endogenously present within the laterodorsal tegmental
nucleus: Functional implications for a role of eCBs in arousal.
AB - Previously, we presented electrophysiological evidence for presence in mice brain
slices of functional cannabinoid type I receptors (CB1Rs) within the laterodorsal
tegmentum (LDT), a brain stem nucleus critical in control of arousal and rapid
eye movement (REM) sleep. Further, using pharmacological agents, we provided data
suggestive of the endogenous presence of cannabinoids (CBs) acting at LDT CB1Rs.
However, in those studies, identification of the type(s) of CB ligands
endogenously present in the LDT remained outstanding, and this information has
not been provided elsewhere. Accordingly, we used the highly-sensitive liquid
chromatography/mass spectrometry (LC-MS) method to determine whether N
arachidonoylethanolamide (Anandamide or AEA) and 2-arachidonyl glycerol (2-AG),
which are both endogenous CB ligands acting at CB1Rs, are present in the LDT.
Mice brain tissue samples of the LDT were assayed using ion trap LC-MS in
selected ion monitoring mode. Chromatographic analysis and product-ion MS scans
identified presence of the CBs, AEA and 2-AG, from LDT mouse tissue. Data using
the LC-MS method show that AEA and 2-AG are endogenously present within the LDT
and when coupled with our electrophysiological findings, lead to the suggestion
that AEA and 2-AG act at electropharmacologically-demonstrated CB1Rs in this
nucleus. Accordingly, AEA and 2-AG likely play a role in processes governed by
the LDT, including control of states of cortical gamma band activity seen in
alert, aroused states, as well as cortical and motor activity characteristic of
REM sleep.
PMID- 28404452
TI - Agrimonia pilosa leaf extract accelerates skin barrier restoration by activation
of transient receptor potential vanilloid 3.
PMID- 28404453
TI - Wip1 inhibition leads to severe pro-inflammatory phenotype in skin in response to
chemical irritation.
PMID- 28404454
TI - Anacardic acid ameliorates ultraviolet irradiation-induced damage to human skin.
PMID- 28404455
TI - Modulation of iTBS after-effects via concurrent directional TDCS: A proof of
principle study.
AB - BACKGROUND: Polarising currents can modulate membrane potentials in animals,
affecting the after-effect of theta burst stimulation (TBS) on synaptic strength.
OBJECTIVE: We examined whether a similar phenomenon could also be observed in
human motor cortex (M1) using transcranial direct current stimulation (TDCS)
during monophasic intermittent TBS (iTBS). METHODS: TDCS was applied during
posterior-anterior iTBS using three different conditions: posterior-anterior TDCS
(anode 3.5 cm posterior to M1, cathode 3.5 cm anterior to M1), anterior-posterior
TDCS (cathode 3.5 cm posterior to M1, anode 3.5 cm anterior to M1), and sham
TDCS. RESULTS: When the direction of TDCS (posterior-anterior) matched the
direction of the electrical field induced by iTBS, we found a 19% non-significant
increase in excitability changes in comparison with iTBS combined with sham TDCS.
When the TDCS was reversed (anterior-posterior), the excitatory effect of iTBS
was abolished. CONCLUSION: Our findings suggest that excitatory after-effects of
iTBS can be modulated by directionally-specific TDCS.
PMID- 28404456
TI - Biotransformation of anabolic compound methasterone with Macrophomina phaseolina,
Cunninghamella blakesleeana, and Fusarium lini, and TNF-alpha inhibitory effect
of transformed products.
AB - Microbial transformation of methasterone (1) was investigated with Macrophomina
phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of
1 with M. phaseolina yielded metabolite 2, while metabolites 3-7 were obtained
from the incubation of 1 with C. blakesleeana. Metabolites 8-13 were obtained
through biotransformation with F. lini. All metabolites, except 13, were found to
be new. Methasterone (1) and its metabolites 2-6, 9, 10, and 13 were then
evaluated for their immunomodulatory effects against TNF-alpha, NO, and ROS
production. Among all tested compounds, metabolite 6 showed a potent inhibition
of proinflammatory cytokine TNF-alpha (IC50=8.1+/-0.9MUg/mL), as compared to
pentoxifylline used as a standard (IC50=94.8+/-2.1MUg/mL). All metabolites were
also evaluated for the inhibition of NO production at concentration of 25MUg/mL.
Metabolites 6 (86.7+/-2.3%) and 13 (62.5+/-1.5%) were found to be the most potent
inhibitors of NO as compared to the standard NG-monomethyl-l-arginine acetate
(65.6+/-1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and
3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro
inflammatory cytokine TNF-alpha, as well as NO production makes them interesting
leads for further studies.
PMID- 28404457
TI - Nerve injury during anterior cruciate ligament reconstruction: A comparison
between patellar and hamstring tendon grafts harvest.
AB - BACKGROUND: Tendon harvesting for anterior cruciate ligament reconstruction often
injures sensory branches of the saphenous nerve. The reports on the prevalence of
these injuries are scarce, while the implications on patient satisfaction are not
known. Our objective was to compare the prevalence of sensory nerve injuries in
patellar to hamstring autograft harvesting for anterior cruciate ligament
reconstructions and follow up their postoperative course. METHODS: Between 2012
and 2014, patients who had a primary anterior cruciate ligament reconstruction
with bone patellar tendon bone or hamstring autografts were included (n=94). We
evaluated and compared demographic details, level of activity and postoperative
sensation disturbances between both groups. Data was analyzed retrospectively.
RESULTS: The mean postoperative follow-up time was 23months. At the last follow
up 46 (77%) patients of the patellar tendon group and 22 (58%) of the hamstring
tendons group reported on reduced sensation; however, in both groups a quarter of
these patients experienced full recovery within an average of seven to eight
months. There were more patients in the hamstring tendons group that reported on
partial recovery. In most cases midline incisions for patellar tendons harvesting
injured the infrapatellar branch and medial incisions for hamstring tendons
harvesting injured the sartorial branch of the saphenous nerve. CONCLUSIONS:
Harvesting tendon autografts for anterior cruciate ligament reconstructions by
vertical incisions had high prevalence of saphenous nerve branches injury with a
minor possibility for complete recovery within the first year. The loss of
sensation was perceived by patients as a minor complication. LEVEL OF EVIDENCE:
Level IV, therapeutic case series.
PMID- 28404458
TI - A comparison of accurate automatic hippocampal segmentation methods.
AB - The hippocampus is one of the first brain structures affected by Alzheimer's
disease (AD). While many automatic methods for hippocampal segmentation exist,
few studies have compared them on the same data. In this study, we compare four
fully automated hippocampal segmentation methods in terms of their conformity
with manual segmentation and their ability to be used as an AD biomarker in
clinical settings. We also apply error correction to the four automatic
segmentation methods, and complete a comprehensive validation to investigate
differences between the methods. The effect size and classification performance
is measured for AD versus normal control (NC) groups and for stable mild
cognitive impairment (sMCI) versus progressive mild cognitive impairment (pMCI)
groups. Our study shows that the nonlinear patch-based segmentation method with
error correction is the most accurate automatic segmentation method and yields
the most conformity with manual segmentation (kappa=0.894). The largest effect
size between AD versus NC and sMCI versus pMCI is produced by FreeSurfer with
error correction. We further show that, using only hippocampal volume, age, and
sex as features, the area under the receiver operating characteristic curve
reaches up to 0.8813 for AD versus NC and 0.6451 for sMCI versus pMCI. However,
the automatic segmentation methods are not significantly different in their
performance.
PMID- 28404460
TI - Consumption of coffee and tea with add-ins in relation to daily energy, sugar,
and fat intake in US adults, 2001-2012.
PMID- 28404459
TI - Preparation of Pseudomonas aeruginosa alginate-flagellin immunoconjugate.
AB - Mucoid strains of Pseudomonas aeruginosa are closely associated with chronic
pulmonary infections. In this report we describe a straightforward approach to
conjugate high molecular weight alginate to type b-flagellin (FLB) and
investigation of its bioactivity. The conjugation process was performed by using
ADH and EDAC. The endotoxin was eliminated from the candidate vaccine by LPS
removal resin followed by LAL test. The bioconjugate molecules were verified by
simultaneously determination of polysaccharide/protein content followed by gel
filtration chromatography and FTIR spectroscopy. Groups of eight BALB/c mice were
injected intranasally with 5 MUg (per each nostril) of purified alginate, FLB and
conjugated alginate-FLB with two week intervals. The functional activity of the
vaccine was evaluated by ELISA and opsonophagocytosis tests. Vaccination with the
alginate-FLB conjugate induced a significant (P = 0.0033) rise in alginate
specific IgG in mice. At all dilution ranges, the opsonic activity of the
conjugate vaccine antisera was significantly higher than alginate alone (61.9%
vs. 17.3% at 1:4 dilution; P = 0.0067). The alginate-FLB conjugate could elicit
high specific antibodies titer against alginate by improving its immunogenicity.
In addition, the antisera raised against conjugate vaccine act as a suitable
opsonin for phagocytosis of the mucoid strains of P. aeruginosa.
PMID- 28404461
TI - Experiences and perspectives of mothers of the pertussis vaccination programme in
London.
AB - BACKGROUND: In 2012, a pertussis outbreak prompted a national vaccination
programme for pregnant women, which provides passive protection for infants.
Vaccine uptake in London is consistently lower than elsewhere in the UK. There
are few studies looking at the reasons why pregnant women accept or refuse
pertussis vaccination. Therefore, this study aimed to gain a better understanding
of London women's views and experiences, to identify how services might be
improved. STUDY DESIGN: Cross-sectional qualitative semi-structured interviews
study. METHODS: Purposive sampling of four London boroughs was made, taking
boroughs in different geographical locations, with varying levels of deprivation
and pertussis vaccine uptake. Participants were recruited through baby clinics
and interviews conducted covering knowledge about pertussis, the vaccine,
information given during pregnancy, factors influencing decision-making,
experience of vaccination, future intentions in another pregnancy and
recommendations for improving uptake. A thematic analysis approach was used.
RESULTS: A total of 42 interviews were conducted. Five main themes were
identified: (1) lack of discussion about pertussis; (2) desire to protect the
baby; (3) trust in health professionals; (4) convenience of vaccination; and (5)
help navigating 'busyness of pregnancy'. This study found that, if offered, most
women would accept vaccination. Although vaccination through the general
practitioner was convenient, more options for vaccination, such as through
antenatal clinics, might increase uptake. Despite usage of the internet to look
up medical information, women wanted to discuss vaccination with their midwives
or general practitioners. Women wanted a simple pregnancy 'checklist' to help
ensure that they had received all recommended aspects of antenatal care including
vaccination. CONCLUSION: Poor uptake of vaccine is not always due to lack of
demand or active refusals. Service providers have an important role to play in
actively promoting vaccination services, ensuring women have access to the
information they require and in increasing the availability and access to
vaccination programmes.
PMID- 28404462
TI - Trends of lack of health insurance among US adults aged 18-64 years: findings
from the Behavioral Risk Factor Surveillance System, 1993-2014.
AB - OBJECTIVE: To examine the prevalence of lack of health insurance and its changes
over time among adult residents (aged 18-64 years) in 50 states and the District
of Columbia (DC). STUDY DESIGN: Cross-sectional surveys. METHODS: We aggregated
annual state-based Behavioral Risk Factor Surveillance System (BRFSS) data from
1993 through 2014 to provide nationwide and state-based prevalence estimates for
lack of insurance among adults aged 18-64 years. The adjusted prevalence was
estimated using log-linear regression analyses with a robust variance estimator
after controlling for demographic variables. The trend was assessed separately
for the periods 1993-2010 and 2011-2014 due to methodologic changes in the BRFSS.
RESULTS: From 1993 through 2010, the adjusted prevalence of lack of health
insurance increased by 0.54% (P < 0.0001) annually (range: 16.3% in 1995 to 19.1%
in 2005); this prevalence decreased significantly in 2014 (15.1%). In 2014,
Georgia, Mississippi, and Texas had the highest adjusted prevalences (range: 23.0
24.6%) of lack of health insurance, and DC, Massachusetts, and Rhode Island had
the lowest (range: 6.2-10.1%). The changes in the prevalence of lack of insurance
over time varied significantly by state. CONCLUSIONS: The nationwide prevalence
of lack of health insurance decreased significantly in the past few years,
especially in 2014 when about one-seventh of Americans aged 18-64 years reported
lack of health insurance coverage. The huge variations in the prevalence of lack
of health insurance and its changes over time among states suggest continuing
efforts to ensure healthcare access for all Americans are needed to improve the
overall health of the population.
PMID- 28404463
TI - Changes over time in mental well-being, fruit and vegetable consumption and
physical activity in a community-based lifestyle intervention: a before and after
study.
AB - OBJECTIVES: There is a theoretical basis for believing that healthy lifestyle
interventions can improve mental well-being and evidence to show that mental well
being is protective of future health. This study contributes to the evidence base
by examining changes in mental well-being associated with the One Body One Life
(OBOL) healthy lifestyle programme in a community setting in the West Midlands.
STUDY DESIGN: Quantitative, before and after the evaluation. METHODS: We
conducted a before and after study of the lifestyle intervention 'OBOL', a multi
component intervention that includes exercise and healthy eating education.
Mental well-being was measured with the Warwick-Edinburgh Mental Well-being
Scale. Physical activity and fruit and vegetable consumption were self-reported.
Measures were collected before and after the 12-week intervention and three
months post completion. Non-parametric tests were used to assess differences
between groups, and linear mixed models were used to assess change over time.
RESULTS: Four hundred and eighty-one (81% of attendees) adult participants
completed a valid Warwick-Edinburgh Mental Well-being Scale before starting OBOL;
of whom, 63.8% completed the Warwick-Edinburgh Mental Well-being Scale
immediately post intervention and 25.2% at three months. Mental well-being levels
increased significantly (P < 0.001) over the course of the intervention and were
sustained at the three-month follow-up (baseline median Warwick-Edinburgh Mental
Well-being Scale score = 48 [interquartile range 41-55], completion = 53
[interquartile range 46-57], 3-month follow-up = 52 [interquartile range 46-56]).
Change in mental well-being was clinically significant after accounting for age
and gender. Changes in both fruit and vegetable consumption and physical activity
appeared to explain some but not all of the variation in mental well-being.
CONCLUSION: We found significant improvements in mental well-being among
participants directly after the intervention which were sustained at the three
month follow-up. These findings contribute to a growing body of knowledge on the
contribution of lifestyle interventions to promoting and sustaining mental well
being.
PMID- 28404464
TI - Density of day cares in relation to reported pertussis incidence in Philadelphia.
AB - OBJECTIVES: Reported pertussis incidence has increased markedly in recent years.
In addition to the documented increase in under-immunization and waning immunity,
the increase may be related to the more frequent use of child care services by
parents over the last few decades. Additionally, clustering of outbreaks may be
related to neighborhood characteristics not previously identified. STUDY DESIGN:
We conducted a citywide case-control study of children in Philadelphia aged birth
through six years, between 2001 and 2013. Cases were reported as probable
pertussis diagnoses to the Health Department. Controls were sampled from the
city's immunization information system and matched to the cases by date of birth.
METHODS: Multilevel logistic regression was used to isolate the independent
contributions of individual and neighborhood risk factors and the corresponding
relative odds of pertussis. The density of day cares in each neighborhood served
as the main exposure and reported incident cases of confirmed and probable
pertussis was the main outcome. RESULTS: Between 2001 and 2013, 410 cases of
confirmed and probable pertussis were included with four controls matched per
case yielding a final sample of 2050 children from 45 Philadelphia neighborhoods.
There was a 30% increase in the risk of pertussis based solely on the
neighborhood where the children resided (median odds ratio 1.3, 95% credible
interval 1.1, 1.6). The density of day cares in each neighborhood was unrelated
to the distribution of pertussis cases. CONCLUSIONS: Pertussis clustering was
observed at the neighborhood level in Philadelphia, but was unrelated to the
neighborhood's day care density. From a Health Department perspective, the
highest risk neighborhoods should be targeted for vaccine campaigns and further
research to identify the etiologic risk factors.
PMID- 28404465
TI - Tool for decision-making regarding general evacuation during a rapid river flood.
AB - OBJECTIVES: To propose a simple and effective tool for decision-making regarding
general evacuation during a rapid river flood. STUDY DESIGN: Virtual testing of a
tool in a real event. METHOD: A four-component tool was applied to build an
alternative scenario of the catastrophic river flood in Obrenovac, Serbia, on May
2014. The components of this tool are: (1) the amount of precipitation above the
95th percentile of all previous measurements; (2) upstream river discharge above
the 95th percentile of all previous measurements; (3) upstream river level above
the 95th percentile of all previous measurements; and (4) worsening of the
hydrometeorological situation in the following 48 h. RESULTS: In the early
morning of 16 May 2014, a rapid river wave flooded 80% of the Obrenovac
territory. There were 13 deaths due to drowning. Application of the study tool
shows that these lives could have been saved, as the score to recommend general
evacuation was reached 1 day before the flooding. The application of this tool to
two previous great floods in Serbia shows that the score to recommend general
evacuation was reached either 1 day before or on the onset of flash flooding.
CONCLUSIONS: Due to its simplicity, this tool is universally applicable to
facilitate decision-making regarding general evacuation during a rapid river
flood, and it should be further tested in future similar catastrophes.
PMID- 28404466
TI - Factors affecting the quality of life among Chinese rural general residents: a
cross-sectional study.
AB - OBJECTIVES: The brief version of the World Health Organization's Quality of Life
Instrument (WHOQOL-BREF) is widely used for evaluating the personal subjective
quality of life (QOL) of patients and particular populations. However, in the
absence of sufficient studies among the general population, normative data for
WHOQOL-BREF remain scarce. To fill this gap, the present study explored more
sociodemographic and health-related factors affecting the QOL. STUDY DESIGN: In
total, 11,351 participants aged >=35 years in rural areas of Liaoning Province
were screened with a stratified cluster multistage sampling scheme in 2012-2013.
Anthropometric measurements, laboratory examinations, and self-reported
information on disease history were collected by trained personnel. Depression
symptoms were assessed using the Patient Health Questionnaire-9. METHODS:
Stepwise multiple linear regression was used to explore the association between
multiple factors and QOL. RESULTS: Females and single/widowed subjects had lower
QOL scores than males and married/cohabiting subjects, respectively. Total QOL
scores and scores for each domain decreased as age increased, but a positive
correlation was found between age and the environmental domain score.
Participants with higher annual incomes, education levels, and activity levels
had higher QOL scores. In the regression model, the coefficient for stroke was
2.17 (95% confidence interval [CI] -2.64, -1.71) for the total QOL score. For a
one-level increase in depression level, the total QOL score decreased by 5.62
(95% CI -5.83 to -5.42), physical domain score decreased by 1.63 (95% CI -1.69 to
-1.58), and psychological domain score decreased by 1.81 (95% CI -1.87 to -1.75).
CONCLUSIONS: Socio-economic status including marital status is highly related to
QOL. Regarding chronic diseases, stroke is an important factor of QOL and
depressive symptoms have a strong negative relationship with QOL.
PMID- 28404467
TI - Association of perceived physical and social attributes with neighborhood
satisfaction among men and women in disadvantaged communities.
PMID- 28404468
TI - Assessing the impact of a program for late surgical intervention in early-blind
children.
AB - OBJECTIVE: Many blind children in the developing world are unable to obtain
timely treatment due to lack of financial and medical resources. Can public
health programs that identify and treat such children several years after the
onset of blindness enhance their quality of life? The notion that visual
development is subject to an early 'critical period' argues against this
possibility. However, there are inadequate empirical data from humans on this
issue. To address this need, we examined the quality of life of children living
in India and who were treated for early-onset blindness (before one year of age),
due to cataracts or corneal opacities. STUDY DESIGN: Survey study. METHODS: As
part of an ongoing scientific effort named Project Prakash, we screened over
40,000 children in rural northern India to identify those suffering from early
onset blindness. They were provided eye surgeries in a tertiary care ophthalmic
center in New Delhi. We subsequently surveyed 64 Prakash children, ranging in age
from 5 to 22 years and obtained their responses on a multi-dimensional quality of
life questionnaire. RESULTS: Nearly all of the subjects indicated that their
quality of life had improved after treatment. Children reported marked
enhancement in their mobility, independence, and safety, and also in social
integration. Surprisingly, we found no significant correlations between quality
of life metrics and factors such as age at treatment, gender, time since
treatment, and pre-surgery and post-surgery acuity. CONCLUSIONS: A key question
for public health policy makers is whether a program of surgical intervention for
older blind children is likely to be beneficial, or if the resources are better
spent on rehabilitation via vocational training and assistive devices. The marked
improvements in quality of life we find in our data strongly argue for the
provision of surgical care regardless of a child's age.
PMID- 28404469
TI - Hepatitis B virus infection in Aseer Region, south-western Saudi Arabia: a call
for an immediate action against a preventable disease.
AB - OBJECTIVES: The present study was designed as a large-scale cross-sectional study
to cast some light on the magnitude of hepatitis B virus (HBV) infection in Aseer
Region, south-western Saudi Arabia, a region reported to be of the highest
endemicity. METHODS: During the WHO hepatitis day of 2013, an aggressive health
education campaign was launched in all the hospitals and primary health care
centres in Aseer Region. Posters were distributed to encourage the local
population to visit the health facilities to be tested for HBV. They were
interviewed using a structured questionnaire. Detection of hepatitis B surface
antigen (HBsAg) was done using a fourth-generation ELISA kits. RESULTS: The
present study included 10,234 persons. The study revealed an overall
seroprevalence of 5.9% (95% confidence interval [CI] = 5.5-6.4%). A
seroprevalence of 0.8% (95% CI = 0.2-2.1%) was found among persons aged less than
15 years, and a seroprevalence of 1.3% (95% CI = 0.4-2.9%) was found among
persons aged 15-24 years. On the other hand, among persons aged 25 years and over
(who were born before the expanded programme on immunization [EPI]), a
seroprevalence of 6.3% (95% CI = 5.8-6.8%) was found. Pockets of unvaccinated
individuals were identified. CONCLUSION: The present study has documented the
efficacy of vaccination in protecting against HBV infection. It also identified
the presence of pockets of unvaccinated persons requiring further investigations.
Aggressive health education programmes and 'catch-up' mass vaccination of those
aged over 25 years is mandatory.
PMID- 28404470
TI - Use of enhancement drugs amongst athletes and television celebrities and public
interest in androgenic anabolic steroids. Exploring two Peruvian cases with
Google Trends.
PMID- 28404471
TI - Waterpipe tobacco smoking prevalence and illegal underage use in waterpipe
serving premises: a cross-sectional analysis among schoolchildren in Stoke-on
Trent.
AB - OBJECTIVES: Waterpipe tobacco smoking has received little epidemiological and
policy attention in the UK despite reports of increasing prevalence alongside an
anecdotally non-compliant industry. This study aimed to determine how waterpipe
tobacco smoking is changing among young people in the UK, both in terms of
prevalence and sociodemographic correlates of use, and to quantify the extent of
illegal underage use in waterpipe-serving premises in the UK. STUDY DESIGN:
Repeat cross-sectional. METHODS: A secondary analysis of two cross-sectional
surveys (total N = 3376), conducted in 2013 and 2015 among secondary school
students aged 11-16 years in Stoke-on-Trent, measured lifetime (both surveys) and
regular (at least monthly; 2015 survey only) waterpipe tobacco prevalence and
location of usual use. Logistic regression models measured the association
between independent variables (age, sex, ethnicity, presence of free school
meals, cigarette smoking status) with lifetime and regular waterpipe tobacco use,
and with illegal underage use; the latter defined as usually smoking waterpipe
tobacco in a waterpipe-serving premise. RESULTS: Lifetime waterpipe tobacco
prevalence remained similar in 2013 (13.7%, 95% confidence interval [CI] 12.0
15.4%) and 2015 (14.6%, 95% CI 12.8-16.4%), whereas regular use was measured at
2.9% (95% CI 2.1-3.8%) in 2015. Older, non-white, males who concurrently used
cigarettes had higher odds of lifetime waterpipe tobacco use. Illegal underage
use was reported among 27.1% of all regular users, correlates of which included
increasing age and South Asian ethnicity. The presence of free school meals was
not associated with lifetime or regular waterpipe tobacco prevalence, nor illegal
underage use. CONCLUSIONS: Increased monitoring of waterpipe tobacco prevalence
and patterns, including the underage policy compliance of waterpipe-serving
premises, is needed to help inform policy decisions to control waterpipe tobacco
use.
PMID- 28404472
TI - The prevalence of latent tuberculosis infection in rural Jiangsu, China.
AB - OBJECTIVES: Diagnosis and interventional treatment of latent tuberculosis (TB)
infection (LTBI) are important components in tuberculosis control. But systematic
studies regarding the epidemic of LTBI are still rare in China. The objective of
this study was to assess the prevalence and risk factors associated with LTBI
based on the results of a domestic TB-specific gamma interferon (IFN-gamma)
release assay (TB-IGRA) in rural Jiangsu, China. STUDY DESIGN: Cross-sectional
study of subjects registered in eight villages in Jiangsu, China. METHODS: This
study was conducted in 2012 in eight villages. After recruitment, individuals
with active TB or a history of TB were excluded. The TB-IGRA was performed for
diagnosis of LTBI. RESULTS: 2169 of 2185 subjects met the requirement and were
analysed in this study. 524 (24.3%) had a positive result, and positive rate
gradually increased with age (P for trend <0.001). Multivariate analyses showed
that increasing age, male gender and a history of TB exposure were risk factors
associated with LTBI. Bacillus Calmette-Guerin (BCG) vaccination did not reduce
the risk of TB infection in participants (aged >=20 years). CONCLUSIONS: The
findings of this study demonstrate that the prevalence of LTBI in China might be
overestimated by tuberculin skin test compared with IFN-gamma release assay
(IGRA). The degree of TB exposure is related to Mycobacterium tubercuium (MTB)
infection, and BCG vaccination offers little protection against MTB infection in
adults. The early and effective detection and treatment of active TB patients,
and screening and intervention for LTBI patients with a high risk of developing
active TB could be cost-effective methods for TB control in China.
PMID- 28404473
TI - Coding accuracy for Parkinson's disease hospital admissions: implications for
healthcare planning in the UK.
AB - OBJECTIVES: Hospital Episode Statistics data are used for healthcare planning and
hospital reimbursements. Reliability of these data is dependent on the accuracy
of individual hospitals reporting Secondary Uses Service (SUS) which includes
hospitalisation. The number and coding accuracy for Parkinson's disease hospital
admissions at a tertiary centre in Birmingham was assessed. STUDY DESIGN:
Retrospective, routine-data-based study. METHODS: A retrospective electronic
database search for all Parkinson's disease patients admitted to the tertiary
hospital over a 4-year period (2009-2013) was performed on the SUS database using
International Classification of Disease codes, and on the local inpatient
electronic prescription database, Prescription and Information Communications
System, using medication prescriptions. Capture-recapture methods were used to
estimate the number of patients and admissions missed by both databases. RESULTS:
From the two databases, between July 2009 and June 2013, 1068 patients with
Parkinson's disease accounted for 1999 admissions. During these admissions, the
Parkinson's disease was coded as a primary or secondary diagnosis. Ninety-one
percent of these admissions were recorded on the SUS database. Capture-recapture
methods estimated that the number of Parkinson's disease patients admitted during
this period was 1127 patients (95% confidence interval: 1107-1146). A
supplementary search of both SUS and Prescription and Information Communications
System was undertaken using the hospital numbers of these 1068 patients. This
identified another 479 admissions. SUS database under-estimated Parkinson's
disease admissions by 27% during the study period. CONCLUSION: The accuracy of
disease coding is critical for healthcare policy planning and must be improved.
If the under-reporting of Parkinson's disease admissions on the SUS database is
repeated nationally, expenditure on Parkinson's disease admissions in England is
under-estimated by approximately L61 million per year.
PMID- 28404474
TI - Does having a difficult child lead to poor maternal mental health?
AB - OBJECTIVES: Considerable evidence suggests maternal psychopathology influences
that of their offspring. The probability of a reverse causal pathway has been
only rarely considered but is a concern, given around 10% of children manifest
mental impairment during their early years. This study determines the extent to
which child behavior problems at ages 5 and 14 years are associated with mothers'
mental health at 21 years post birth. STUDY DESIGN: Longitudinal study. METHODS:
Data were taken from a sample of 3650 women from Mater and University of
Queensland Study of Pregnancy birth cohort. Women's mental health was measured
using the Mental Disorder Screening Tool at 21 years post birth. The Child
Behavior Check List was used to measure internalizing, combined
social/attention/thought disorder, and aggression at the age of 5 and 14 years.
Logistic regression was used to derive odds ratios and 95% confidence intervals.
A number of confounders were used to test for independence. RESULTS: Following
all adjustments, child internalizing behaviors and combined
social/attention/thought disorder at 5 years, and all measures of child behavior
problem at 14 years were associated with mothers meeting criteria for mental
health impairment at 21 years post birth. Moreover mothers of children with
behavior problems at 14 years were approximately 2-3 times more likely to these
meet these criteria. CONCLUSIONS: Mothers of children with behavior problems at 5
and 14 years of age were more likely to have mental health impairment at 21 years
post birth. Child health professionals should be cognizant of the mother-child
relationship having mutual mental health vulnerability.
PMID- 28404475
TI - Exploring the short-term impact of community water fluoridation cessation on
children's dental caries: a natural experiment in Alberta, Canada.
AB - OBJECTIVES: Dental caries (tooth decay) is common and can be serious. Dental
caries is preventable, and community water fluoridation is one means of
prevention. There is limited current research on the implications of fluoridation
cessation for children's dental caries. Our objective was to explore the short
term impact of community water fluoridation cessation on children's dental
caries, by examining change in caries experience in population-based samples of
schoolchildren in two Canadian cities, one that discontinued community water
fluoridation and one that retained it. STUDY DESIGN: We used a pre-post cross
sectional design. METHODS: We examined dental caries indices (deft [number of
decayed, extracted, or filled primary teeth] and DMFT [number of decayed,
missing, or filled permanent teeth]) among grade 2 schoolchildren in 2004/05 and
2013/14 in two similar cities in the province of Alberta, Canada: Calgary
(cessation of community water fluoridation in 2011) and Edmonton (still
fluoridated). We compared change over time in the two cities. For Calgary only,
we had a third data point from 2009/10, and we considered trends across the three
points. RESULTS: We observed a worsening in primary tooth caries (deft) in
Calgary and Edmonton, but changes in Edmonton were less consistent and smaller.
This effect was robust to adjustment for covariates available in 2013/14 and was
consistent with estimates of total fluoride intake from biomarkers from a
subsample. This finding occurred despite indication that treatment activities
appeared better in Calgary. The worsening was not observed for permanent teeth.
For prevalence estimates only (% with >0 deft or DMFT), the three data points in
Calgary suggest a trend that, though small, appears consistent with an adverse
effect of fluoridation cessation. CONCLUSIONS: Our results suggest an increase in
dental caries in primary teeth during a time period when community fluoridation
was ceased. That we did not observe a worsening for permanent teeth in the
comparative analysis could reflect the limited time since cessation. It is
imperative that efforts to monitor these trends continue.
PMID- 28404476
TI - Body size ideals and dissatisfaction in Ghanaian adolescents: role of media,
lifestyle and well-being.
AB - OBJECTIVES: To inspire effective health promotion campaigns, we tested the
relationship of ideal body size and body size dissatisfaction with (1) the
potential resulting health-influencing factors diet, physical activity and well
being; and (2) with media as a potential influencer of body ideals. STUDY DESIGN:
This is a cross-sectional study in 370 Ghanaian adolescents (aged 11-18 years).
METHODS: Questionnaires included disordered eating (EAT26), diet quality (FFQ),
physical activity (IPAQ), well-being (KINDL) and media influence on appearance
(SATAQ: pressure, internalisation and information). Ideal body size and body size
dissatisfaction were assessed using the Stunkard figure rating scale. Body mass
index (BMI), skinfolds and waist were measured. Linear regressions were adjusted
for gender, age and parental education. Also, mediation was tested: 'can
perceived media influence play a role in the effects of actual body size on body
size dissatisfaction?'. RESULTS: Body size dissatisfaction was associated with
lower well-being and more media influence (pressure and internalisation) but not
with physical activity, diet quality or disordered eating. An underweight body
size ideal might worsen disordered eating but was not significantly related to
the other predictors of interest. Only a partial mediation effect by media
pressure was found: especially overweight adolescents felt media pressure, and
this media pressure was associated with more body size dissatisfaction.
CONCLUSIONS: To prevent disordered eating and low well-being, health messages
should include strategies that reduce body size dissatisfaction and increase body
esteem by not focussing on the thin body ideal. Changing body size ideals in the
media might be an appropriate way since media pressure was a mediator in the BMI
dissatisfaction relation.
PMID- 28404477
TI - Perceptions and attitudes about body weight and adherence to the physical
activity recommendation among adolescents: the moderating role of body mass
index.
AB - OBJECTIVE: We examined the associations between perceptions and attitudes about
body weight and adherence to the physical activity recommendation (PAR) for
adolescents to achieve >=60 min/day of moderate-to-vigorous physical activity and
tested whether body mass index (BMI) was a moderator of these relationships.
STUDY DESIGN: Cross-sectional survey. METHODS: Self-reported data from Canadian
adolescents (n = 4299) who participated in the 2013 Ontario Student Drug Use and
Health Survey were analysed. RESULTS: Dissatisfaction with body weight was
associated with lower odds of adherence to the PAR (odds ratio [OR]: 0.74; 95%
confidence interval [CI]: 0.55-0.99). More specifically, those who perceived
themselves as overweight/obese had lower odds of adherence to the PAR (OR: 0.59;
95% CI: 0.42-0.81) compared with those who think they were about the right
weight. Those who were trying to gain weight were more likely to adhere to the
PAR (OR: 1.92; 95% CI: 1.29-2.86) compared to those who were doing nothing about
their body weight. BMI was a significant moderator of the association between
dissatisfaction with body weight and adherence to the PAR. At low BMI, there were
no differences in the adherence to the PAR between adolescents who were
dissatisfied with their body weight or not. At high BMI, adolescents who were
dissatisfied with their body weight were less likely to adhere to the PAR than
those who were not dissatisfied with their weight. Results were not different
between males and females. CONCLUSIONS: Results suggest that adolescents who are
dissatisfied with their body weight have lower adherence to the PAR, particularly
those who are overweight or obese.
PMID- 28404478
TI - Factors affecting participation decision and amount of physical activity among
urban dwellers in Malaysia.
AB - OBJECTIVES: The rapid rise in the prevalence of physical inactivity-related
diseases has become a serious public health issue worldwide. The objective of the
present study is to examine the factors affecting participation in physical
activity among urban dwellers in Malaysia. STUDY DESIGN: This cross-sectional
study measures physical activity using a rigorous regression model. METHODS: Data
are obtained from the National Health and Morbidity Survey 2011 (NHMS 2011). A
lognormal hurdle model is used to analyse the participation decision and the
amount decision of physical activity. RESULTS: The results show that income,
gender, ethnicity, marital status and employment status are significantly
associated with participation decision and amount decision. However, age,
insurance and self-rated health only affect participation decision, whereas
family size, education and smoking only affect amount decision. CONCLUSIONS: It
can, thus, be concluded that sociodemographic, insurance, lifestyle and health
factors play an important role in determining physical activity behaviour among
urban dwellers. When formulating policies, special attention must be paid to
these factors.
PMID- 28404479
TI - Effectiveness of regionalization of trauma care services: a systematic review.
AB - OBJECTIVES: Improving trauma systems in various forms has always been an
important aspect of health policy. While several papers have reported the
implementation of a structured trauma system of care, research evidence on the
effectiveness of such regionalization for improvement in trauma outcome is
limited. STUDY DESIGN: Systematic review. METHOD: Medline, EMbase, EconLit and
Health Management Information Consortium were searched, using sensitive search
terms, for interventional studies that reported a trauma regionalization system
as their intervention, and compared important outcomes such as mortality and
preventable deaths. At least two authors assessed eligibility for inclusion and
risk of bias, and extracted data from the included studies. As meta-analysis was
not possible for all studies, two controlled before-after studies were included
in the meta-analysis, and a narrative analysis was conducted for the other
studies. RESULTS: After title and abstract sifting, 66 papers were retrieved.
After reading the full texts, a total of 24 studies from the USA, UK, Canada,
Australia, and the Netherlands were included in this review. In spite of
variation in study specifications, most were before-after studies with a high
risk of bias. Although a reduction in mortality was shown in most studies, only
two studies were eligible for meta-analysis, and the results showed a significant
reduction in mortality after implementation of an organized trauma system (odds
ratio 0.840, 95% confidence interval 0.756-0.924; P = 0.00). CONCLUSION:
Correlation was found between a regionalized network of trauma care and a
reduction in trauma-related mortality, based on studies that did not exclude the
effects of other concurrent changes on observed reductions. It is recommended
that more studies with robust research designs should be conducted in a more
diverse range of countries to assess the effectiveness of regionalization.
Despite this limitation, the present findings support the regionalization of
trauma care services.
PMID- 28404480
TI - 2D and 3D FISH of expanded repeat RNAs in human lymphoblasts.
AB - The first methods for visualizing RNAs within cells were designed for simple
imaging of specific transcripts in cells or tissues and since then significant
technical advances have been made in this field. Today, high-resolution images
can be obtained, enabling visualization of single transcript molecules,
quantitative analyses of images, and precise localization of RNAs within cells as
well as co-localization of transcripts with specific proteins or other molecules.
In addition, tracking of RNA dynamics within single cell has become possible. RNA
imaging techniques have been utilized for investigating the role of mutant RNAs
in a number of human disorders caused by simple microsatellite expansions. These
diseases include myotonic dystrophy type 1 and 2, amyotrophic lateral
sclerosis/frontotemporal dementia, fragile X-associated tremor/ataxia syndrome,
and Huntington's disease. Mutant RNAs with expanded repeats tend to aggregate
predominantly within cell nuclei, forming structures called RNA foci. In this
study, we demonstrate methods for fluorescent visualization of RNAs in both fixed
and living cells using the example of RNAs containing various expanded repeat
tracts (CUG, CCUG, GGGGCC, CGG, and CAG) from experiment design to image
analysis. We describe in detail 2D and 3D fluorescence in situ hybridization
(FISH) protocols for imaging expanded repeats RNAs, and we review briefly live
imaging techniques used to characterize RNA foci formed by mutant RNAs. These
methods could be used to image the entire cellular pathway of RNAs, from
transcription to degradation.
PMID- 28404481
TI - Clinical utility and diagnostic accuracy of palm-held, mini-sized
ultrasonocardiographic scanner in congenital heart disease.
AB - BACKGROUND/PURPOSE: To investigate whether a palm-held ultrasonocardiographic
scanner would be useful for screening and follow-up in congenital heart disease
(CHD). METHODS: We retrospectively reviewed the echocardiographic images from
June 1, 2014 to November 1, 2014. All patients underwent two ultrasonographic
examinations including palm-held scanner examination and standard
echocardiography. To compare the quality of the two instruments, we developed a
diagnostic scoring system ranging from 1 point to 10 points, with 10 points
indicating the best quality. Two experienced echocardiographers retrospectively
reviewed all recorded images blindedly and gave each examination a score.
Comparisons of diagnostic score between two equipments were performed. RESULTS: A
total of 262 patients' images were reviewed. All cardiac lesions could be
detected with both instruments. The mean diagnostic score of palm-held scanner
and standard echocardiography were 8.20+/-0.53 versus 9.64+/-0.37 (p<0.05) in
color image and 7.00+/-1.05 versus 8.56+/-1.14 (p<0.05) in gray-scale two
dimensional image, respectively. When we compared the score between the two
instruments in individual CHDs, we found standard echocardiography had better
quality except for detecting muscular ventricular septal defect and pulmonary
regurgitation. CONCLUSION: The diagnostic sensitivity of palm-held scanner in
detecting CHD was very good. Despite both instruments having a high diagnostic
score in detecting CHD, standard echocardiography had better quality. Traditional
echocardiography is still the standard tool for CHD evaluation. However, the palm
held scanner can support physical examination for initial screening and follow
up, and offer cardiologists an opportunity to visualize and listen to the heart
at any time.
PMID- 28404482
TI - Plasmid dynamics in Vibrio parahaemolyticus strains related to shrimp Acute
Hepatopancreatic Necrosis Syndrome (AHPNS).
AB - Vibrio parahaemolyticus is a causative agent of acute hapatopancreatic necrosis
syndrome (AHPNS) which causes early mortality in white shrimp. Emergence of AHPNS
has caused tremendous economic loss for aquaculture industry particularly in Asia
since 2010. Previous studies reported that strains causing AHPNS harbor a 69-kb
plasmid with possession of virulence genes, pirA and pirB. However, genetic
variation of the 69-kb plasmid among AHPNS related strains has not been
investigated. This study aimed to analyze genetic composition and diversity of
the 69-kb plasmid in strains isolated from shrimps affected by AHPNS. Plasmids
recovered from V. parahaemolyticus strain VPE61 which represented typical AHPNS
pathogenicity, strain VP2HP which did not represent AHPNS pathogenicity but was
isolated from AHPNS affected shrimp and other AHPNS V. parahaemolyticus isolates
in Genbank were investigated. Protein coding genes of the 69-kb plasmid from the
strain VPE61 were identical to that of AHPNS strain from Vietnam except the
inverted complement 3.4-kb transposon covering pirA and pirB. The strain VP2HP
possessed remarkable large 183-kb plasmid which shared similar protein coding
genes to those of the 69-kb plasmid from strain VPE61. However, the 3.4-kb
transposon covering pirA and pirB was absent from the 183-kb plasmid in strain
VP2HP. A number of protein coding genes from the 183-kb plasmid were also
detected in other AHPNS strains. In summary, this study identified a novel 183-kb
plasmid that is related to AHPNS causing strains. Homologous recombination of the
69-kb AHPNS plasmid and other naturally occurring plasmids together with loss and
gain of AHPNS virulence genes in V. parahaemolyticus were observed. The outcome
of this research enables understanding of plasmid dynamics that possibly affect
variable degrees of AHPNS pathogenicity.
PMID- 28404483
TI - Anaconda paramyxovirus infection in an adult green anaconda after prolonged
incubation: Pathological characterization and whole genome sequence analysis.
AB - From July 2011 to June 2012, 31 out of 33 green anaconda juveniles from an
oceanarium in Hong Kong died over a 12-month period. These anacondas were progeny
of a female anaconda purchased from Japan and added to the collection in May
2011. The juvenile anacondas were born in July 2011. A novel paramyxovirus, named
anaconda paramyxovirus (AnaPV), was isolated from these affected juvenile
anacondas. In July 2015, one of the remaining two anacondas, that survived the
cluster of fatal infections, died at the age of four. Pathologically, both the
death of the four-year-old anaconda and the previous deaths of the anaconda
juveniles involved multiple, similar organs. However, the organ that was
primarily affected in the juvenile anacondas that died in 2011 was the kidney,
whereas the most remarkable lesions in the four-year-old anaconda involved the
lungs. Granulomas previously observed in the juvenile anacondas with AnaPV
infections were not obvious in the four-year-old anaconda. RT-PCR for the L gene
of AnaPV was positive for the lungs, kidneys, ovary, spleen, liver, tracheal
content and gall bladder of the four-year-old anaconda, with a median viral load
of 1.32*106AnaPVRNAcopies/mg. Complete genome sequencing revealed that there were
only 12-14 nucleotide changes in the AnaPV genome of the four-year old anaconda
compared to those of the AnaPV found in anaconda juveniles in 2011/2012. Among
these nucleotide changes, only four were non-synonymous mutations, with one in
the N gene, one in the M gene and two in the HN gene. Both epidemiological and
molecular data supported that the four-year-old green anaconda probably acquired
the AnaPV from its mother or its siblings that died 3-4years ago, and its death
is a result of an unprecedented extended incubation period or latency of AnaPV
followed by a subsequent manifestation of clinical disease and death.
PMID- 28404484
TI - Health research capacity building in Georgia: a case-based needs assessment.
AB - OBJECTIVES: Research capacity building in the health sciences in low- and middle
income countries (LMICs) has typically focused on bench-science capacity, but
research examining health service delivery and health workforce is equally
necessary to determine the best ways to deliver care. The Republic of Georgia,
formerly a part of the Soviet Union, has multiple issues within its healthcare
system that would benefit from expended research capacity, but the current
research environment needs to be explored prior to examining research-focused
activities. The purpose of this project was to conduct a needs assessment focused
on developing research capacity in the Republic of Georgia with an emphasis on
workforce and network development. STUDY DESIGN: A case study approach guided by
a needs assessment format. METHODS: We conducted in-country, informal, semi
structured interviews in English with key informants and focus groups with
faculty, students, and representatives of local non-governmental organizations.
Purposive and snowball sampling approaches were used to recruit participants,
with key informant interviews scheduled prior to arrival in country. Documents
relevant to research capacity building were also included. Interview results were
coded via content analysis. Final results were organized into a SWOT (strengths,
weaknesses, opportunities, threat) analysis format, with the report shared with
participants. RESULTS: There is widespread interest among students and faculty in
Georgia around building research capacity. Lack of funding was identified by many
informants as a barrier to research. Many critical research skills, such as
proposal development, qualitative research skills, and statistical analysis, were
reported as very limited. Participants expressed concerns about the ethics of
research, with some suggesting that research is undertaken to punish or 'expose'
subjects. However, students and faculty are highly motivated to improve their
skills, are open to a variety of learning modalities, and have research
priorities aligned with Georgian health needs. CONCLUSIONS: This study's findings
indicate that while the Georgian research infrastructure needs further
development, Georgian students and faculty are eager to supplement its gaps by
improving their own skills. These findings are consistent with those seen in
other developing country contexts.
PMID- 28404485
TI - State-level gonorrhea rates and expedited partner therapy laws: insights from
time series analyses.
AB - OBJECTIVE: In this study, we examined state-level monthly gonorrhea morbidity and
assessed the potential impact of existing expedited partner therapy (EPT) laws in
relation to the time that the laws were enacted. STUDY DESIGN: Longitudinal
study. METHODS: We obtained state-level monthly gonorrhea morbidity (number of
cases/100,000 for males, females and total) from the national surveillance data.
We used visual examination (of morbidity trends) and an autoregressive time
series model in a panel format with intervention (interrupted time series)
analysis to assess the impact of state EPT laws based on the months in which the
laws were enacted. RESULTS: For over 84% of the states with EPT laws, the monthly
morbidity trends did not show any noticeable decreases on or after the laws were
enacted. Although we found statistically significant decreases in gonorrhea
morbidity within four of the states with EPT laws (Alaska, Illinois, Minnesota,
and Vermont), there were no significant decreases when the decreases in the four
states were compared contemporaneously with the decreases in states that do not
have the laws. CONCLUSION: We found no impact (decrease in gonorrhea morbidity)
attributable exclusively to the EPT law(s). However, these results do not imply
that the EPT laws themselves were not effective (or failed to reduce gonorrhea
morbidity), because the effectiveness of the EPT law is dependent on necessary
intermediate events/outcomes, including sexually transmitted infection service
providers' awareness and practice, as well as acceptance by patients and their
partners.
PMID- 28404487
TI - Investigation on the role of consumer health orientation in the use of food
labels.
AB - OBJECTIVE: This study explored the relationship between health orientation (i.e.
individual motivation to engage in healthy attitudes, beliefs and behaviours) and
consumers' use of nutritional information on food labels. Specifically, this
study analysed the relationship between a number of direct investments in health
(namely those behaviours that can contribute directly to maintain a good health
status) and use of nutritional information on food labels. STUDY DESIGN: Data for
the analysis were collected through face-to-face interviews with a sample of 540
Italian consumers in charge of their grocery shopping. Forty grocery stores,
including supermarkets and hypermarkets, were selected using a systematic
sampling technique. METHODS: Data were analysed using three equations and
accounting for endogeneity issues. RESULTS: This study found that those consumer
groups with low health orientation (specifically smokers, those who do not
exercise regularly, and those with an unhealthy body weight) show little interest
in nutritional labels. CONCLUSION: Nutritional labels as a tool to promote
healthier food choices have a limited effect on those consumers in greatest need
of pursuing healthier lifestyle habits. Alternative policy intervention should be
undertaken to reach these consumer groups.
PMID- 28404486
TI - Adherence to and effects on physical function parameters of a community-based
standardised exercise programme for overweight or obese patients carried out by
local sports clubs.
AB - OBJECTIVES: To evaluate the adherence to a sports-club-based standardised real
life exercise programme for overweight or obese patients. The effects on physical
function parameters, anthropometry and quality of life were also assessed. STUDY
DESIGN: Within this prospective cohort study data from patients in Austrian
sports-club-based programmes were analysed. METHODS: Sports-club-based programmes
were held twice a week and carried out by local trainers. The target group was
overweight or obese patients. Adherence was determined after 2 and 6 months, and
physical function parameters were evaluated at baseline and after 2 months.
RESULTS: A total of 71 patients (age: 52.0; standard deviation [SD: 12.1] years;
body mass index [BMI]: 37.3 [SD: 8.2] kg/m2) took part in the study. Within the
first 2 months the adherence rate was 62%, while 20% (14/71) participated in
>=75% of all offered sessions. After 6 months, 49% (17/35) of the retained sample
still participated regularly in an exercise class. At baseline, muscle strength
represented only 70% of the age- and sex-specific reference values and could be
increased in a range from +4.0% (1.3 [SD: 3.0] kg; muscular endurance for the
pectoral muscles) to +22.5% (16.1 [SD: 17.5] kg) (muscular endurance for the
lower limb muscles). Concerning endurance capacity, the heart rate for a constant
submaximal workload decreased from 126.4 (SD: 21.7) beats per minute at baseline
to 120.9 (SD: 21.1) after 2 months (P < 0.001). CONCLUSIONS: Sports clubs, as a
non-clinical setting, can offer attractive standardised exercise programmes for a
minority of overweight or obese patients. Long term changes in life-style, that
result in sufficient levels of health enhancing physical activity still remain a
huge public health challenge.
PMID- 28404488
TI - Understanding differences between caregivers and non-caregivers in completer
rates of Chronic Disease Self-Management Program.
AB - OBJECTIVES: The Chronic Disease Self-Management Program (CDSMP) was developed to
advance participants' self-care of chronic illness and may be offered to both
individuals with chronic conditions and their caregivers. Previous studies of
CDSMP have identified multiple resulting health benefits for participants as well
as factors associated with participants' completion rates. This study
investigated differences on these issues between caregiving and non-caregiving
participants. STUDY DESIGN: Secondary analysis using regression analysis to
predict the outcome. METHODS: Baseline data were collected directly from adult
(over 18 years) participants of CDSMP workshops in New York State from 2012 to
2015 (n = 2685). Multi-level logistic regression analysis was used to compare the
difference on completion of workshops (attended four or more of sessions) and
contributing factors with the independent variable of whether participants
provided care/assistance to a family member or friends with long-term illness or
disability. Additional individual-level variables controlled for in the model
were age, gender, race/ethnicity, living arrangement, education, the number of
chronic conditions and disabilities; as were workshop-level characteristics of
class size, language used, workshop leader experience, location urbanity and
delivery site type. RESULTS: Participants who provided care to family or friends
were 28% more likely to complete the workshop compared with those who did not
(odds ratio = 1.279, P < 0.05). Different factors influenced the completion of
CDSMP workshop for caregivers and non-caregivers. CONCLUSIONS: People who provide
care to others appeared to have stronger motivation to complete the workshops
with greater benefits. Agencies offering CDSMP should encourage caregivers to
attend.
PMID- 28404489
TI - The effectiveness of suicide prevention programmes: urban and gender disparity in
age-specific suicide rates in a Taiwanese population.
AB - OBJECTIVE: The effectiveness of suicide prevention programmes is an important
issue worldwide today. The impact of urbanization and gender is controversial in
suicide rates. Hence, this study adjusted on potential risk factors and secular
changes for suicide rates in gender and rural/urban areas. STUDY DESIGN:
Observational study. METHODS: A Suicide Prevention Center was established by the
Executive Yuan in Taiwan in 2005 and tried to carry out suicidal intervention in
the community in every city and town. There were two phases, including the first
phase of the programme from 2005 to 2008, and the second phase of the programme
from 2009 to 2013. The crude suicide rates data from the period of 1991-2013,
which recruited nine urban and 14 rural areas in Taiwan, were extracted from the
Taiwanese national mortality data file. The suicide rates in two areas of Taiwan
(Taipei city and Yilan County) were further used to compare the differences
between urban and rural areas. RESULTS: The results show that unemployment
increased the suicide rate in men aged 45-64 years and in women older than 65
years of age in Taiwan. High divorce and unemployment rates resulted in increased
suicide rates in men in the city, whereas emotional distress was the main cause
of suicides in men in rural areas. The main method of suicide was jumping from a
high building for both sexes in the city, whereas drowning was the most common
method of suicide for men in rural areas. CONCLUSION: Following the intervention
programme, suicide behaviour began to decrease in all urban and rural areas of
Taiwan. This study showed the cumulative effect of the intervention programme in
decreasing the suicide rate in Taiwan. Moreover, the gender-specific suicidal
rate and disparity in suicidal methods in urban and rural areas should be
considered in further preventive strategies in Taiwan.
PMID- 28404490
TI - Social support mediates the relationships between extraversion, neuroticism, and
cognitive function in older adults.
AB - OBJECTIVES: We supplement existing findings on a link between social support and
cognitive function in later life by considering the role of personality as an
antecedent to both, and of social support as a mediator of the link between
personality and cognitive function. STUDY DESIGN: An observational cohort study.
METHODS: We evaluated social support using the Lubben Social Network Scale,
across 624 adults aged over 60 years, and investigated this measure as a mediator
of the relationships between extraversion and neuroticism at baseline 2007-2009,
and cognitive function at follow-up, 2 years later. A half-longitudinal mediation
design, within a structural equation modelling framework, was used. RESULTS:
There was a direct effect of extraversion, such that lower levels were related to
higher scores of cognitive function. There was no significant direct effect of
neuroticism on cognitive function at follow-up. Social support partially mediated
the paths between both extraversion and neuroticism and cognitive function at
follow-up. Decomposing the mediation effects by using social support subscales
(measuring support from friends, relatives and neighbours) showed meaningful
indirect effects for both predictors. CONCLUSION: Results suggest that social
support may offer a target for interventions for cognitively at-risk older adults
and add to the existing empirical evidence describing the link between
personality and cognitive function.
PMID- 28404491
TI - Hypertension and correlates among Montenegrin schoolchildren-a cross-sectional
study.
AB - OBJECTIVES: In one of the few national studies of children in a former Eastern
bloc country emerging as a Western democracy and the first such study ever in
Montenegro, this study establishes the prevalence and correlates of childhood
hypertension (CH). STUDY DESIGN: A cross-sectional national study. METHODS: The
study was conducted with 3254 children aged 7-13 years (50.3% male) from 39
elementary schools. We used a structured questionnaire to gather sociodemographic
information as well as data on factors potentially related to CH. Children's
nutritional status was assessed using the criteria of the International Obesity
Task Force. Waist circumference was also measured. Blood pressure was measured in
schools using an oscillometric monitor. CH was defined as an average systolic
blood pressure and/or diastolic blood pressure greater than or equal to the 95th
percentile for sex, age, and height. RESULTS: The prevalence of CH was 10.4% with
no differences between boys and girls. Multiple regression revealed that the odds
for child hypertension were lowered by 10% for each year of age. On the other
hand, rural environment and child obesity raised the odds of hypertension by 38%
and 68%, respectively. CONCLUSIONS: We found hypertension in one out of ten
Montenegrin schoolchildren, with no gender differences. Obesity and rural areas
may be unfriendly to children's blood pressure.
PMID- 28404492
TI - Overweight and obesity in Indonesia: prevalence and risk factors-a literature
review.
AB - OBJECTIVES: Overweight/obesity is a problem faced by both high- and low- and
middle-income countries. This review aimed to report published data on the
prevalence of overweight and obesity in Indonesian children, adolescents, and
adults, along with the associated risk factors. STUDY DESIGN: Literature review.
METHODS: We conducted a literature search for articles published in English
(through Medline via OvidSP, Scopus, Global Health via OvidSP and Web of Science
electronic databases) and Indonesian languages (several websites, direct contact
with Indonesian public health researchers, practitioners and Ministry of Health
staff) from earliest to March 2016. We screened the results and ensured the
quality of included studies with Loney's tools for critically appraising
prevalence or incidence studies. RESULTS: We included 17 papers on the topic
which were available in full text and passed the critical appraisal process. The
prevalence of overweight/obesity has increased over the past two decades in
Indonesian children, adolescents and adults. Prevalence rates are higher in boys
than girls among children, but higher in females in the adolescent and adult age
groups. The prevalence of overweight/obesity is also higher in those living in
urban areas and with higher income or education. CONCLUSIONS: Overweight/obesity
is a serious public health problem in Indonesia with a continuing increase in its
prevalence. Interventions at the household level and beyond are needed to
successfully lower the prevalence of overweight/obesity in the country.
PMID- 28404493
TI - Relationships between depression, pain and sleep quality with doctor visits among
community-based adults in north-west China.
AB - OBJECTIVES: Previous studies have suggested that the high rates of unmet need for
mental health services in China among depressed people are related to a cultural
tendency to deny mental and emotional symptoms and instead express them
somatically. Such somatization may lead a sufferer to a consultation with a
healthcare professional but rarely leads to appropriate mental health treatment.
This study aimed to elucidate the relationships of depression, sleep quality and
perceived physical pain with doctor visits among community-based adults in China,
and thus to help guide the development of clinical practices aimed at reducing
unmet mental health service need. STUDY DESIGN: Cross-sectional study. METHODS:
In total, 7602 north-west Chinese adults aged >40 years were included in the
survey. The Center for Epidemiologic Studies Depression Scale-Chinese Edition was
used to assess depressive symptoms. Subjective sleep quality was evaluated using
the Pittsburgh Sleep Quality Index. The Brief Pain Inventory-Chinese Version was
used to measure pain severity and pain interference. RESULTS: In this study,
16.2% of people reported physical pain, and 20.0% of those who reported poor
sleep quality had seen a doctor in the past month. Only 14.4% of those with
depression had seen a doctor. The results of the logistic regression analyses
indicated that subjects with pain were significantly more likely to have seen a
doctor than subjects without pain (odds ratio [OR] 1.61; 95% confidence interval
[CI] 1.32-1.97). Poor sleep quality was significantly associated with doctor
visits (OR 1.76, 95% CI 1.40-2.21). Depression was not associated with doctor
visits after adjusting for pain, sleep quality and potentially confounding
factors. CONCLUSION: When attempting to screen for depression and risk of
depression in middle-aged and older adults in China, mental health professionals
should focus on perceived physical pain and poor sleep quality.
PMID- 28404494
TI - Association between preterm birth and its subtypes and maternal sociodemographic
characteristics during the post-transitional phase in a developing country with a
very high human development index.
AB - OBJECTIVES: Chile is a post-transitional country evolving towards a stationary
population pyramid, which may be associated with increasing preterm birth (PTB)
rates. This study aimed to compare maternal sociodemographic characteristics
between the start of the post-transition phase (1994) and an established stage
(2013) and to evaluate associations between these characteristics and PTB. STUDY
DESIGN: An observational analytic design was conducted using national birth
records (n = 4,956,311). METHODS: Variables analysed in the 20 birth cohorts from
1994 to 2013 were: length of gestation (preterm <37 weeks) subdivided by
gestational age (extreme, moderate/severe and late); maternal age (<=19, 20-35
and >35 years); education level (<8, 8-12 and >12 years of education);
employment; marital status; area of residence; and type of birth (singleton,
twins, and triplets or higher order). The prevalence of PTB was expressed as a
percentage, and associations between PTB and predictor variables were analysed
using logistic regression models. RESULTS: Education level, age >35 years,
maternal employment, unmarried status, twin delivery and urban residency rates
increased between 1994 and 2013. According to the adjusted models, age >35 years
and delivery of more than two foetuses were risk factors for all PTB subtypes.
Maternal employment was a risk factor for moderate/severe, late and total PTB,
and a low level of education was a risk factor for late and total PTB. On the
other hand, age <=19 years was protective against all PTB subtypes. CONCLUSIONS:
All maternal characteristics changed between 1994 and 2013. Furthermore, the
prevalence of PTB increased for all predictor variables studied over this period.
PMID- 28404495
TI - Assessing the potential effectiveness of oral health promotion strategies in
primary health care in Brazil.
PMID- 28404496
TI - Association between seroprevalence of measles and various social determinants in
the year following a measles outbreak in Turkey.
AB - OBJECTIVES: Despite an ongoing measles elimination programme, a measles outbreak
occurred in 2013 in Turkey. Population-based seroprevalence studies are needed to
determine seronegativity and explore the reasons for this outbreak. This study
aimed to explore the seroprevalence of measles and its association with various
social determinants in a provincial population in Turkey in the year following a
measles outbreak. STUDY DESIGN: Cross-sectional study. METHODS: This study was
conducted in Manisa Province in 2014 in a sample of 1740 people aged >2 years.
The dependent variable was the seroprevalence of measles. Independent variables
were sex, age, migration, household size, household density, income, education
level, existence of chronic disease and occupational class. Blood samples were
collected from participants at family health centres. The presence of specific
measles antibodies in serum samples was determined using an anti-measles virus
IgG enzyme-linked immunosorbent assay test. Chi-squared test and logistic
regression analysis were performed. RESULTS: Overall, data from 1250 people were
analysed. The seroprevalence of measles in the whole study population was 82.2%
(95% confidence interval 80.0-84.2). Seroprevalence was 55.4% among subjects aged
2-9 years, 48.7% among subjects aged 10-19 years, 74.1% among subjects aged 20-29
years and 93.6% among subjects aged 30-39 years (P < 0.01). Seroprevalence in
subjects aged >40 years was >95%. The lowest seroprevalence was found in primary
school children (40.2%), followed by those below the age for primary education
(69.8%) and secondary school graduates (75.1%). The prevalence of measles
seronegativity was not associated with any of the social determinants when
adjusted for age. CONCLUSIONS: The seroprevalence of measles was lower than
expected in the study population and was particularly low in subjects aged <30
years of age despite previous vaccination. Seroprevalence was not associated with
social determinants of health that confirmed either an even distribution of virus
exposure or fair access to vaccination services. However, the current
seroprevalence cannot be sufficiently effective to reach the measles elimination
targets, suggesting that it may be necessary to re-evaluate the need for an extra
dose of measles vaccine.
PMID- 28404498
TI - Prevalence of e-cigarette use among adolescents in 13 Eastern European towns and
cities.
PMID- 28404497
TI - Magnitude of and gender differences in cardiovascular risk profiles among
community residents in Shenzhen, China.
AB - OBJECTIVES: Understanding the prevalence of cardiovascular disease (CVD) risk
factors has an impact on the public policy for initiating CVD prevention. This
study aimed to examine the prevalence of current smoking, overweight/obesity,
hypertension, diabetes mellitus (DM), and dyslipidemia among Shenzhen residents
and to investigate gender differences in CVD risk profiles to identify the
subgroups at higher risk. STUDY DESIGN: A large cross-sectional study was
conducted between April and May 2015. METHODS: Using multistage cluster random
sampling methods, a total of 1784 residents finished the face-toface interview
survey. Physical examinations and blood tests were performed by qualified
professionals. RESULTS: The prevalence of current smoking, overweight/obesity,
hypertension, DM, and dyslipidemia were 21.8%, 40.6%, 17.6%, 4.8%, and 35.7%,
respectively. Clustering of two or more or three or more of CVD risk factors was
noted in 35.7% and 14.1% of participants. The prevalence of current smoking
(45.0% vs 1.1%, P < 0.001), overweight/obesity (48.5% vs 33.4%, P < 0.001),
hypertension (19.7% vs 15.7%, P < 0.05), and dyslipidemia (46.5% vs 20.5%, P <
0.001) was found higher among male than among female participants. CONCLUSIONS:
This study adds to the evidence suggesting high prevalence rates of CVD risk
factors and composite measures among Shenzhen residents. The higher level of CVD
risk factors in male than in female residents is suggested. Effective population
based intervention programs such as smoking cessation, early detection,
management, and treatment of hypertension, DM, and dyslipidemia should be
initiated and enhanced especially among the males.
PMID- 28404499
TI - The Scottish adolescent e-cigarette user: profiling from the Scottish Schools
Adolescent Lifestyle and Substance Use Survey (SALSUS).
PMID- 28404500
TI - Psychosocial job stressors and thoughts about suicide among males: a cross
sectional study from the first wave of the Ten to Men cohort.
AB - OBJECTIVES: Psychosocial job stressors are known to be associated with poor
mental health. This research seeks to assess the relationship between
psychosocial working conditions and suicidal ideation using a large dataset of
Australian males. STUDY DESIGN: Cross-sectional study. METHODS: Data from wave 1
of the Australian Longitudinal Study on Male Health (Ten to Men) was used to
assess the association between suicidal ideation in the past two weeks and
psychosocial working conditions using logistic regression. The sample included
11,052 working males. The exposures included self-reported low job control, high
job demands, job insecurity and low fairness of pay. We controlled for relevant
confounders. RESULTS: In multivariable analysis, persons who were exposed to low
job control (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26, P =
0.003), job insecurity (OR 1.69, 95% CI 1.44-1.99, P < 0.001) and unfair pay (OR
1.19, 95% CI 1.11-1.27, P < 0.001) reported elevated odds of thoughts about
suicide. Males employed casually or on fixed-term contracts reported higher odds
of suicidal ideation (OR 1.32, 95% CI 1.09-1.61, P = 0.005). CONCLUSION:
Psychosocial job stressors are highly prevalent in the working population and
workplace suicide prevention efforts should aim to address these as possible risk
factors.
PMID- 28404501
TI - Development and validation of measures to evaluate adolescents' knowledge about
human papillomavirus (HPV), involvement in HPV vaccine decision-making, self
efficacy to receive the vaccine and fear and anxiety.
AB - OBJECTIVES: We describe the development and validation of measures of human
papillomavirus (HPV)/HPV vaccination knowledge, fear/anxiety about vaccination,
involvement in HPV vaccine decision-making, and self-efficacy with regard to
getting the vaccine, designed to evaluate the efficacy of an intervention to
affect these domains (collectively termed the HAVIQ: HPV Adolescent Vaccine
Intervention Questionnaire). STUDY DESIGN: Literature search, cognitive
interviews and cross-sectional survey. METHODS: A literature search identified
existing items that were modified for the present measures. Experts reviewed
draft measures for face and content validity. Cognitive interviews with
adolescents were also used to assess content validity. Adolescents completed the
measures and an internal reliability analysis of each measure was performed.
RESULTS: The four experts concurred that the measures had face validity.
Cognitive interviews identified items requiring refinement. Content validity was
examined with ten experts and was deemed acceptable. There were 1800 adolescents
who completed the measures; Cronbach's alpha was >0.6 for three of the four
measures. The four final measures are brief, comprising 25 items in total.
CONCLUSIONS: The measures are robustly developed and validity-tested. The HAVIQ
may be used in research settings to evaluate adolescents' knowledge and
experiences of the process of HPV vaccination in a school-based vaccination
programme.
PMID- 28404502
TI - Modelling adverse treatment outcomes of HIV-infected adolescents attending public
sector HIV clinics in Lusaka.
AB - BACKGROUND: In resource-limited setting, there is scarce evidence comparing
antiretroviral therapy (ART) outcomes among HIV-infected adolescents to that of
other age groups. METHODS AND STUDY DESIGN: We analysed data from 25 ART
facilities in Lusaka District, comparing treatment-naive ART-eligible young
adolescents (10-14 years), older adolescents (15-19) and young adults (20-24
years) initiating first-line ART to those aged 24 years or older. The adjusted
relative risk (RR) of failure to achieve an adequate CD4 response (defined as
failure to increase CD4 count by >= 50 cells/mm3 at 6 months or by >= 100
cells/mm3) at 6 or 12 months after ART initiation was modelled using log-binomial
regression. The effect of age group on mortality and loss to follow-up (LTFUP;
>=60 days since scheduled visit date) was estimated using adjusted Cox
proportional hazards models, respectively. This was a routine retrospective
design using program data. RESULTS: Of the 94,023 patients initiating ART from
May 2004 to February 2011, 1303 (1.4%) were young adolescents, 1440 (1.5%) were
older adolescents and 5825 (6.2%) were young adults. 85,455 (90.9%) were 24 years
or older at the time of ART initiation. Compared with adults, both young
adolescents (RR: 0.88, 95% confidence interval [CI]: 0.76-1.01 at 6 months and
RR: 0.80, 95% CI: 0.69-0.93 at 12 months) and older adolescents (RR: 0.82, 95%
CI: 0.71-0.95 at 6 months) were less likely to achieve adequate CD4 response. No
evidence of a difference in mortality risk was observed among older adolescents
(hazard ratio [HR] 1.20, 95% CI: 0.93-1.56) compared with adults; however, there
was a reduced risk of mortality in young adolescents compared with adults (HR:
0.61, 95% CI: 0.40-0.92). Young adolescents were less likely to be LTFUP
following ART initiation (HR: 0.74, 95% CI: 0.59-0.92), while older adolescents
and young adults were reported to be more likely to drop out of care (HR: 1.54
95% CI: 1.33-1.78; HR: 1.51 95% CI: 1.40-1.63 respectively). CONCLUSION: Older
adolescents and young adults had poorer ART treatment outcomes, including failure
to achieve adequate CD4 recovery and failure to remain in long-term care, when
compared with adults. Interventions are necessary to help increase outcomes and
retention in care.
PMID- 28404503
TI - Physical mobility, physical activity, and obesity among elderly: findings from a
large population-based Swedish survey.
AB - OBJECTIVE: To examine how physical activity and physical mobility are related to
obesity in the elderly. STUDY DESIGN: A cross-sectional study of 2558 men and
women aged 65 years and older who participated in a population survey in 2012 was
conducted in mid-Sweden with an overall response rate of 67%. METHODS: Obesity
(body mass index >=30 kg/m2) was based on self-reported weight and height, and
physical activity and physical mobility on questionnaire data. Chi-squared test
and multiple logistic regressions were used as statistical analyses. RESULTS: The
overall prevalence of obesity was 19% in women and 15% in men and decreased after
the age of 75 years. A strong association between both physical activity and
obesity, and physical mobility and obesity was found. The odds for obesity were
higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence
interval [CI] 2.14-3.75) than for physical inactivity (OR 1.63, 95% CI 1.28-2.08)
when adjusted for gender, age, socio-economic status and fruit and vegetable
intake. However, physical activity was associated with obesity only among elderly
with physical mobility but not among those with impaired physical mobility.
CONCLUSION: It is important to focus on making it easier for elderly with
physical mobility to become or stay physically active, whereas elderly with
impaired physical mobility have a higher prevalence of obesity irrespective of
physical activity.
PMID- 28404504
TI - Burden of asymptomatic malaria among a tribal population in a forested village of
central India: a hidden challenge for malaria control in India.
AB - OBJECTIVE: Chhattisgarh in India is a malaria-endemic state with seven southern
districts that contributes approximately 50-60% of the reported malaria cases in
the state every year. The problem is further complicated due to asymptomatic
malaria cases which are largely responsible for persistent transmission. This
study was undertaken in one of the forested villages of the Keshkal subdistrict
in Kondagaon district to ascertain the proportion of the population harbouring
subclinical malarial infections. STUDY DESIGN: Community-based cross-sectional
study. METHODS: Mass blood surveys were undertaken of the entire population of
the village in the post-monsoon seasons of 2013 and 2014. Fingerprick blood
smears were prepared from individuals of all ages to detect malaria infections in
their blood. Individuals with fever at the time of the survey were tested with
rapid diagnostic tests, and parasitaemia in thick blood smears was confirmed by
microscopy. Malaria-positive cases were treated with anti-malarials in accordance
with the national drug policy. RESULTS: Peripheral blood smears of 134 and 159
individuals, including children, were screened for malaria infection in 2013 and
2014, respectively. Overall, the malaria slide positivity rates were 27.6% and
27.7% in 2013 and 2014, respectively, and the prevalence rates of asymptomatic
malaria were 20% and 22.8%. This study showed that, for two consecutive years,
the prevalence of asymptomatic malaria infection was significantly higher among
children aged <=14 years (34.4% and 34.1% for 2013 and 2014, respectively)
compared with adults (15.2% and 18.2% for 2013 and 2014, respectively; P = 0.023
and 0.04, respectively). CONCLUSION: The number of asymptomatic malaria cases,
especially Plasmodium falciparum, is significant, reinforcing the underlying
challenge facing the malaria elimination programme in India.
PMID- 28404505
TI - Overwork is a silent killer of Chinese doctors: a review of Karoshi in China 2013
2015.
PMID- 28404506
TI - Associations of 24-hour sleep duration and CT-derived measurements of muscle and
bone: The AGES-Reykjavik Study.
AB - BACKGROUND: Although the importance of sleep on preservation of several
physiological functions is well known, the relationship with the two
interconnected tissues - muscle and bone is less understood. OBJECTIVES: This
study aimed to examine the association of 24-hour sleep duration with mid-thigh
muscle composition and proximal femur volumetric bone mineral density (vBMD).
METHODS: 2438 men and 3326 women aged 66 to 96years, residents in the Reykjavik
area, were included in this cross-sectional study. Proximal femur integral vBMD,
mid-thigh muscle area and muscle attenuation were assessed with computed
tomography. Sleep and nap habits were assessed using a questionnaire. RESULTS: We
found that after adjustment for age and BMI long sleep duration (>8h/d) was
negatively associated with thigh lean area in both men (B=-2.21, 95% confidence
interval (CI): -4.01, -0.40) and women (B=-2.39, 95% CI: -3.75, -1.03) and with
muscle attenuation (B=-0.95, 95% CI: -1.47, -0.43) only in women. After
adjustments for age, health and lifestyle factors the association between long
sleep duration and muscle lean area was attenuated and became nonsignificant
while associations with muscle attenuation remained marginally significant (B=
0.51, 95% CI: -1.03, -0.002). Sleep duration was not associated with proximal
femur integral vBMD in the multivariate models. CONCLUSION: Long sleep duration,
particularly in old women, can affect thigh muscle attenuation (increase in
intramuscular fat). Whether optimization of sleep can ameliorate age-associated
intramuscular or intermuscular adipose tissue warrants further studies.
PMID- 28404508
TI - Model-based analyses reveal insular population diversification and cryptic frog
species in the Ischnocnema parva complex in the Atlantic forest of Brazil.
AB - The Atlantic Forest (AF) of Brazil has long been recognized as a biodiversity
conservation hotspot. Despite decades of studies the species inventory of this
biome continues to increase with the discovery of cryptic diversity and the
description of new species. Different diversification mechanisms have been
proposed to explain the diversity in the region, including models of forest
dynamics, barriers to gene flow and dispersal. Also, sea level change is thought
to have influenced coastal diversification and isolated populations on
continental islands. However, the timing and mode of diversification of insular
populations in the AF region were rarely investigated. Here, we analyze the
phylogeography and species diversity of the small-sized direct-developing frog
Ischnocnema parva. These frogs are independent from water bodies but dependent on
forest cover and high humidity, and provide good models to understand forest
dynamics and insular diversification. Our analysis was based on DNA sequences for
one mitochondrial and four nuclear genes of 71 samples from 18 localities
including two islands, Sao Sebastiao, municipality of Ilhabela, and Mar Virado,
municipality of Ubatuba, both in the state of Sao Paulo. We use molecular
taxonomic methods to show that I. parva is composed of six independently evolving
lineages, with the nominal I. parva likely endemic to the type locality. The time
calibrated species tree shows that these lineages have diverged in the Pliocene
and Pleistocene, suggesting the persistence of micro-refuges of forest in the AF.
For the two insular populations we used approximate Bayesian computation to test
different diversification hypotheses. Our findings support isolation with
migration for Sao Sebastiao population, with ~1Mya divergence time, and isolation
without migration for Mar Virado population, with ~13Kya divergence time,
suggesting a combination of different processes for diversification on AF
islands.
PMID- 28404507
TI - Paclitaxel inhibits the activity and membrane localization of PKCalpha and
PKCbetaI/II to elicit a decrease in stimulated calcitonin gene-related peptide
release from cultured sensory neurons.
AB - Peripheral neuropathy is a dose-limiting and debilitating side effect of the
chemotherapeutic drug, paclitaxel. Consequently, elucidating the mechanisms by
which this drug alters sensory neuronal function is essential for the development
of successful therapeutics for peripheral neuropathy. We previously demonstrated
that chronic treatment with paclitaxel (3-5days) reduces neuropeptide release
stimulated by agonists of TRPV1. Because the activity of TRPV1 channels is
modulated by conventional and novel PKC isozymes (c/nPKC), we investigated
whether c/nPKC mediate the loss of neuropeptide release following chronic
treatment with paclitaxel (300nM; 3 and 5days). Release of the neuropeptide,
calcitonin gene-related peptide (CGRP), was measured as an index of neuronal
sensitivity. Following paclitaxel treatment, cultured dorsal root ganglia sensory
neurons were stimulated with a c/nPKC activator, phorbol 12,13-dibutyrate (PDBu),
or a TRPV1 agonist, capsaicin, in the absence and presence of selective
inhibitors of conventional PKCalpha and PKCbetaI/II isozymes (cPKC). Paclitaxel
(300nM; 3days and 5days) attenuated both PDBu- and capsaicin-stimulated release
in a cPKC-dependent manner. Under basal conditions, there were no changes in the
protein expression, phosphorylation or membrane localization of PKC alpha, betaI
or betaII, however, paclitaxel decreased cPKC activity as indicated by a
reduction in the phosphorylation of cPKC substrates. Under stimulatory
conditions, paclitaxel attenuated the membrane translocation of phosphorylated
PKC alpha, betaI and betaII, providing a rationale for the attenuation in PDBu-
and capsaicin-stimulated release. Our findings suggest that a decrease in cPKC
activity and membrane localization are responsible for the reduction in
stimulated peptide release following chronic treatment with paclitaxel in sensory
neurons.
PMID- 28404509
TI - Recycled tetrahedron-like CuCl from waste Cu scraps for lithium ion battery
anode.
AB - The wide applications of metal Cu inevitably resulted in a large quantity of
waste Cu materials. In order to recover the useful Cu under the mild conditions
and reduce the environmental emission, waste Cu scraps were recycled in the form
of CuCl powders with high economic value added (EVA) via the facile hydrothermal
route. The recycled CuCl powders were characterized in terms of scanning electron
microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray
diffraction (XRD). The results suggested that the recycled CuCl powders consisted
of many regular tetrahedron-like micro-particles. Furthermore, in order to reduce
the cost of lithium ion battery (LIB) anode and build the connection of waste Cu
scraps and LIB, the recycled CuCl powders were evaluated as the anode active
material of LIB. As expected, the reversible discharge capacity was about
171.8mAh/g at 2.0C even after 50 cycles, implying the satisfactory cycle
stability. Clearly, the satisfactory results may open a new avenue to develop the
circular economy and the sustainable energy industry, which would be very
important in terms of both the resource recovery and the environmental
protection.
PMID- 28404510
TI - Effects of Fe, Ni, and Fe/Ni metallic nanoparticles on power production and
biosurfactant production from used vegetable oil in the anode chamber of a
microbial fuel cell.
AB - In this study, metallic nanoparticles (Fe, Ni, and Fe/Ni) were used as cathode
catalysts to enhance power production and to improve the anode performance of a
two-chambered microbial fuel cell (MFC). The metallic nanoparticles were rod
shaped and produced by the precipitation/co-precipitation method. A biosurfactant
was produced in the anode chamber of the MFC from used vegetable oil by the
bacteria Serratia sp. Overall cell voltage, power density, bacterial growth, and
biosurfactant production were studied by applying different types of metallic
nanoparticles to the cathode electrode. The influence of various types of
nanoparticles on the impedance of the MFC was also investigated by
electrochemical impedance spectroscopy (EIS), including analyses of anode
impedance, cathode impedance, anode solution resistance, cathode solution
resistance, and membrane resistance. The nanoparticles improved MFC performance
in the following order: Fe>Ni>Fe/Ni. The addition of 1.5mg/cm2 Fe nanoparticles
to the cathode surface enhanced power production by over 500% to 66.4mW/m3,
promoted bacterial growth and biosurfactant production in the anode solution by
132.5% and 32.0%, respectively, and reduced anode impedance, cathode impedance,
and membrane resistance by 26.8%, 81.6%, and 33.8% to 159.00Omega, 7.69Omega, and
261.09Omega, respectively. For the first time, biosurfacant production in the
anode chamber of the MFC was promoted by using the metallic nanoparticles as
cathode catalysts. By improving the cathode properties, this study showed a new
way to manipulated the performance of the anode chamber of the MFC.
PMID- 28404511
TI - Optimization of torrefaction conditions of coffee industry residues using
desirability function approach.
AB - The aim of the present study is to analyze the influence of independent process
variables such as temperature, residence time, and heating rate on the
torrefaction process of coffee chaff (CC) and spent coffee grounds (SCGs).
Response surface methodology and a three-factor and three-level Box-Behnken
design were used in order to evaluate the effects of the process variables on the
weight loss (WL) and the Higher Heating Value (HHV) of the torrefied materials.
Results showed that the effects of the three factors on both responses were
sequenced as follows: temperature>residence time>heating rate. Data obtained from
the experiments were analyzed by analysis of variance (ANOVA) and fitted to
second-order polynomial models by using multiple regression analysis. Predictive
models were determined, able to obtain satisfactory fittings of the experimental
data, with coefficient of determination (R2) values higher than 0.95. An
optimization study using Derringer's desired function methodology was also
carried out and the optimal torrefaction conditions were found: temperature 271.7
degrees C, residence time 20min, heating rate 5 degrees C/min for CC and 256.0
degrees C, 20min, 25 degrees C/min for SCGs. The experimental values closely
agree with the corresponding predicted values.
PMID- 28404512
TI - A new approach for concurrently improving performance of South Korean food waste
valorization and renewable energy recovery via dry anaerobic digestion under
mesophilic and thermophilic conditions.
AB - Dry semicontinuous anaerobic digestion (AD) of South Korean food waste (FW) under
four solid loading rates (SLRs) (2.30-9.21kg total solids (TS)/m3day) and at a
fixed TS content was compared between two digesters, one each under mesophilic
and thermophilic conditions. Biogas production and organic matter reduction in
both digesters followed similar trends, increasing with rising SLR. Inhibitor
(intermediate products of the anaerobic fermentation process) effects on the
digesters' performance were not observed under the studied conditions. In all
cases tested, the digesters' best performance was achieved at the SLR of 9.21kg
TS/m3day, with 74.02% and 80.98% reduction of volatile solids (VS), 0.87 and
0.90m3 biogas/kg VSremoved, and 0.65 (65% CH4) and 0.73 (60.02% CH4) m3 biogas/kg
VSfed, under mesophilic and thermophilic conditions, respectively. Thermophilic
dry AD is recommended for FW treatment in South Korea because it is more
efficient and has higher energy recovery potential when compared to mesophilic
dry AD.
PMID- 28404513
TI - Correlation of diabetes mellitus and body weight of adults above the age of 30
years in a medical facility in Ghana.
AB - BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder characterized by
insufficient insulin production or ineffective pancreatic secretions. In Ghana,
the prevalence of DM was estimated to be 6.3% amongst men and women older than 30
years living in the Greater Accra region. The disease can be determined by
various means including the use of the multistix that assesses the presence of
glucose in urine. MATERIALS AND METHODS: In this study, 100 subjects were sampled
made up of 65% males and 35% females whose urine samples were verified using
multistix. RESULTS: Most (63%) of the subjects diagnosed with the disease fell
within the age ranges of 60-69 years and 70-79 years, thus establishing the fact
that the incidence of the disease increases with increasing age and increasing
body mass index (BMI) over above 25kg/m2. Some (44%) had a family history of
diabetes. Other factors such as the socioeconomic status (SES) categories,
physical activity levels and eating habits of the respondents played different
roles in the occurrence of the disease. CONCLUSION: The sex of the individual,
however, did not have a major impact on the occurrence of the disease. This study
confirmed that overweight body (BMI>=25kg/m2) especially of older ages above 50
years of have very strong link with the prevalence of diabetes mellitus.
PMID- 28404514
TI - Postpartum glucose testing, related factors and progression to abnormal glucose
tolerance in a rural population with a known history of gestational diabetes.
AB - AIMS: Gestational diabetes is a strong risk factor for postpartum progression to
glucose intolerance. The aims of the study were to determine rate of postpartum
glucose testing , its related factors and rate of progression to glucose
intolerance in women who underwent postpartum glucose testing after pregnancy
that complicated by gestational diabetes. MATERIALS: this is a retrospective
study and women with gestational diabetes who received prenatal care during 2005
2015 in 3 rural health centers of Khuramshahr (southwestern of Iran) were
enrolled. Gestational diabetes mellitus diagnosed by FPG test only, 75g OGTT or
GCT. The American Diabetes Association(ADA) criteria applied for definition of
postpartum glucose intolerance (pre-diabetes or diabetes) . RESULTS: Mean
duration of follow-up was 29.7 months. BMI>= 25 was detected in 73.3% and 78.7%
of women during pre-pregnancy and postpartum respectively. Overall 45.8% (60/131)
of women received postpartum glucose testing. Rate of progression to abnormal
glucose tolerance was 23.3% (8.5% pre-diabetes and 15.2% diabetes). Advanced
maternal age was associated with postpartum glucose testing (OR 1.066, CI 1.008
1.128, p=0.02). DISCUSSION: high rate of overweight and obesity, sub optimal rate
of postpartum glucose testing and high prevalence of glucose intolerance,
highlights the importance of postpartum screening with a more sensitive test and
implementation of an intervention program to prevent type 2 diabetes in rural
population particularly older women with prior gestational diabetes.
PMID- 28404515
TI - Assessment of cardiovascular risk via atherogenic indices in patients with
bipolar disorder manic episode and alterations with treatment.
AB - OBJECTIVES: Cardiovascular disease is one of the important cause of mortality
among patients with Bipolar Disorder. Castelli Risk index I and II (CRI-I and
II), Atherogenic Index of Plasma (AIP) and Atherogenic coefficient (AC) are new
parameters in assessing cardiovascular risk. In this study we aimed to explore
the status of cardiovascular risk factors and their alterations with treatment in
manic episode. METHODS: Bipolar Disorder inpatients who were in manic episode and
age-gender matched healthy controls were included in the study. CRI-I, CRI-II,
AIP and AC parameters were calculated before and after treatment. The statistical
significance level was accepted as p<0.05. RESULTS: Sixty-eight male patients and
60 healthy controls were included in the study. CRI-I, CRI-II, AIP and AC
parameters showed an increase after treatment (p<0.001 for all parameters). There
was no significant difference between patients and controls in terms of CRI-I and
CRI-II and AC (p=0.129, p=0.573, p=0.129 respectively). Although mean AIP levels
of patients was significantly lower than control group (p=0.031), the
significance disappeared when we compared the patients and controls according to
being in low, medium, and high risk groups (chi2=0.826, p=0.662). CONCLUSIONS:
Even in short term of treatment, antipsychotics have an important role in
developing dyslipidemia and increasing cardiovascular risk. Manic state may have
positive or at least no additional influences on atherogenic risk.
PMID- 28404516
TI - Risk of diabetes according to the metabolic health status and degree of obesity.
AB - AIM: To determine the progression rates from metabolically healthy or unhealthy
normal weight, overweight and obese phenotype to type 2 diabetes (T2D) in a non
diabetic high risk population in Isfahan, Iran. METHODS: T2D incidence during a
mean (SD) follow-up of 10.1 (2.3) years was examined among 1,982 non-diabetic
first-degree relatives (FDR) of patients with T2D 30-70 years old. Participants
were divided into 6 groups based on body mass index and metabolic syndrome
component, except waist circumference, at baseline: metabolically healthy normal
weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy
obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically
unhealthy overweight (MUOW) and metabolically unhealthy obese (MUO). RESULTS: The
MHO, MUOW, and MUO individuals at baseline were associated with incidence of T2D,
independently of age and gender. MHO were 3 times (OR 2.96; 95% CI 1.07, 8.24)
and MUOW were 2.75 times (95% CI 1.17, 6.45) more likely to develop T2D than
those with MHNW. There was excess risk in MUO than MHO (OR 3.86; 95% CI 1.64,
9.11). CONCLUSIONS: Obesity was a risk factor for T2D, even in the absence of any
metabolic abnormalities. Metabolic abnormalities were a stronger predictor of
incident T2D than obesity.
PMID- 28404517
TI - Dysregulation of microRNA biogenesis in the small intestine after ethanol and
burn injury.
AB - Ethanol exposure at the time of burn injury is a major contributor to post-burn
pathogenesis. Many of the adverse effects associated with ethanol and burn injury
are linked to an impaired intestinal barrier. The combined insult causes
intestinal inflammation, resulting in tissue damage, altered tight junction
expression, and increased intestinal permeability. MicroRNAs play a critical role
in maintaining intestinal homeostasis including intestinal inflammation and
barrier function. Specifically, miR-150 regulates inflammatory mediators which
can contribute to gut barrier disruption. The present study examined whether
ethanol and burn injury alter expression of microRNA processing enzymes (Drosha,
Dicer, and Argonaute-2) and miR-150 in the small intestine. Male mice were
gavaged with ethanol (~2.9g/kg) 4h prior to receiving a ~12.5% total body surface
area full thickness burn. One or three days after injury, mice were euthanized
and small intestinal epithelial cells (IECs) were isolated and analyzed for
expression of microRNA biogenesis components and miR-150. Dicer mRNA and protein
levels were not changed following the combined insult. Drosha and Argonaute-2
mRNA and protein levels were significantly reduced in IECs one day after injury;
which accompanied reduced miR-150 expression. To further determine the role of
miR-150 in intestinal inflammation, young adult mouse colonocytes were
transfected with a miR-150 plasmid and stimulated with LPS (100ng/ml). miR-150
overexpression significantly reduced IL-6 and KC protein levels compared to
vector control cells challenged with LPS. These results suggest that altered
microRNA biogenesis and associated decrease in miR-150 likely contribute to
increased intestinal inflammation following ethanol and burn injury.
PMID- 28404519
TI - Proteasome inhibitors to alleviate aberrant IKBKAP mRNA splicing and low
IKAP/hELP1 synthesis in familial dysautonomia.
AB - FD is a rare neurodegenerative disorder caused by a mutation of the IKBKAP gene,
which induces low expression levels of the Elongator subunit IKAP/hELP1 protein.
A rational strategy for FD treatment could be to identify drugs increasing
IKAP/hELP1 expression levels by blocking protein degradation pathways such as the
26S proteasome. Proteasome inhibitors are promising molecules emerging in cancer
treatment and could thus constitute an enticing pharmaceutical strategy for FD
treatment. Therefore, we tested three proteasome inhibitors on FD human olfactory
ecto-mesenchymal stem cells (hOE-MSCs): two approved by the Food and Drug
Administration (FDA) and European Medicines Agency (EMA), bortezomib and
carfilzomib, as well as epoxomicin. Although all 3 inhibitors demonstrated
activity in correcting IKBKAP mRNA aberrant splicing, carfilzomib was superior in
enhancing IKAP/hELP1 quantity. Moreover, we observed a synergistic effect of
suboptimal doses of carfilzomib on kinetin in improving IKBKAP isoforms ratio and
IKAP/hELP1 expression levels allowing to counterbalance carfilzomib toxicity.
Finally, we identified several dysregulated miRNAs after carfilzomib treatment
that target proteasome-associated mRNAs and determined that IKAP/hELP1 deficiency
in FD pathology is correlated to an overactivity of the 26S proteasome.
Altogether, these results reinforce the rationale for using chemical compounds
inhibiting the 26S proteasome as an innovative option for FD and a promising
therapeutic pathway for many other neurodegenerative diseases.
PMID- 28404518
TI - Nanoparticle fullerol alleviates radiculopathy via NLRP3 inflammasome and
neuropeptides.
AB - The present study aimed to evaluate the analgesic effect of the antioxidant
nanoparticle fullerol in a mouse radiculopathy and a dorsal root ganglion (DRG)
culture models. Intervertebral disk degeneration causes significant hyperalgesia
and nerve inflammation. Pain sensitization and inflammatory reaction were
counteracted by fullerol when disk material was bathed in 10 or 100MUM of
fullerol prior to implantation. Immunohistochemistry showed similar massive IBA1
positive macrophage infiltration surrounding implanted disk material among
groups, but IL-1beta and IL-6 expression was decreased in the fullerol treated
group. In the DRG explant culture, after treatment with TNF-alpha, the expression
of IL-1beta, NLRP3, and caspase 1 was significantly increased but this was
reversed by the addition of fullerol. In addition, fullerol also decreased the
expression of substance P and CGRP in the cultured DRGs. Nanoparticle fullerol
effectively counteracts pain sensitization and the inflammatory cascade caused by
disk degeneration.
PMID- 28404520
TI - Nothing more than a pair of curvatures: A common mechanism for the detection of
both radial and non-radial frequency patterns.
AB - Radial frequency (RF) patterns, which are sinusoidal modulations of a radius in
polar coordinates, are commonly used to study shape perception. Previous studies
have argued that the detection of RF patterns is either achieved globally by a
specialized global shape mechanism, or locally using as cue the maximum tangent
orientation difference between the RF pattern and the circle. Here we challenge
both ideas and suggest instead a model that accounts not only for the detection
of RF patterns but also for line frequency patterns (LF), i.e. contours
sinusoidally modulated around a straight line. The model has two features. The
first is that the detection of both RF and LF patterns is based on curvature
differences along the contour. The second is that this curvature metric is
subject to what we term the Curve Frequency Sensitivity Function, or CFSF, which
is characterized by a flat followed by declining response to curvature as a
function of modulation frequency, analogous to the modulation transfer function
of the eye. The evidence that curvature forms the basis for detection is that at
very low modulation frequencies (1-3 cycles for the RF pattern) there is a
dramatic difference in thresholds between the RF and LF patterns, a difference
however that disappears at medium and high modulation frequencies. The CFSF
feature on the other hand explains why thresholds, rather than continuously
declining with modulation frequency, asymptote at medium and high modulation
frequencies. In summary, our analysis suggests that the detection of shape
modulations is processed by a common curvature-sensitive mechanism that is
subject to a shape-frequency-dependent transfer function. This mechanism is
independent of whether the modulation is applied to a circle or a straight line.
PMID- 28404522
TI - Observations on the relationship between anisometropia, amblyopia and strabismus.
AB - We investigated the potential causal relationships between anisometropia,
amblyopia and strabismus, specifically to determine whether either amblyopia or
strabismus interfered with emmetropization. We analyzed data from non-human
primates that were relevant to the co-existence of anisometropia, amblyopia and
strabismus in children. We relied on interocular comparisons of spatial vision
and refractive development in animals reared with 1) monocular form deprivation;
2) anisometropia optically imposed by either contact lenses or spectacle lenses;
3) organic amblyopia produced by laser ablation of the fovea; and 4) strabismus
that was either optically imposed with prisms or produced by either surgical or
pharmacological manipulation of the extraocular muscles. Hyperopic anisometropia
imposed early in life produced amblyopia in a dose-dependent manner. However,
when potential methodological confounds were taken into account, there was no
support for the hypothesis that the presence of amblyopia interferes with
emmetropization or promotes hyperopia or that the degree of image degradation
determines the direction of eye growth. To the contrary, there was strong
evidence that amblyopic eyes were able to detect the presence of a refractive
error and alter ocular growth to eliminate the ametropia. On the other hand,
early onset strabismus, both optically and surgically imposed, disrupted the
emmetropization process producing anisometropia. In surgical strabismus, the
deviating eyes were typically more hyperopic than their fellow fixating eyes. The
results show that early hyperopic anisometropia is a significant risk factor for
amblyopia. Early esotropia can trigger the onset of both anisometropia and
amblyopia. However, amblyopia, in isolation, does not pose a significant risk for
the development of hyperopia or anisometropia.
PMID- 28404523
TI - Structure, synthesis and biological properties of the pentacyclic guanidinium
alkaloids.
AB - The pentacyclic guanidinium alkaloids (PGAs) are a family of marine natural
products that possess a polycyclic guanidine-containing core and a long alkyl
chain tethered spermidine-derived tail that is rarely observed in other natural
products. These natural products exhibit potent activities on a wide range of
organisms and therefore have attracted the attention of many synthetic chemists;
however, the structure-activity relationships and mechanisms of action of PGAs
remain largely elusive. Herein we summarize the structure, synthesis, toxicity
and mechanisms of action of PGAs and highlight their potential as chemical probes
and/or therapeutic leads.
PMID- 28404524
TI - Concise synthesis of artemisinin from a farnesyl diphosphate analogue.
AB - Artemisinin is one of the most potent anti-malaria drugs and many often-lengthy
routes have been developed for its synthesis. Amorphadiene synthase, a key enzyme
in the biosynthetic pathway of artemisinin, is able to convert an oxygenated
farnesyl diphosphate analogue directly to dihydroartemisinic aldehyde, which can
be converted to artemisinin in only four chemical steps, resulting in an
efficient synthetic route to the anti-malaria drug.
PMID- 28404525
TI - The synthesis and evaluation of new butadiene derivatives as tubulin
polymerization inhibitors.
AB - A series of new butadiene derivatives was synthesized and evaluated as tubulin
polymerization inhibitors for the treatment of cancer. The optimal butadiene
derivative, 9a, exhibited IC50 values of 0.056-0.089MUM for five human cancer
cell lines. This paper included a mechanistic study of the antiproliferative
activity, including a tubulin polymerization assay, an examination of
morphological alterations of cancer cells, an analysis of cell cycle arrest and
an apoptosis assay.
PMID- 28404526
TI - Stereospecific cholinesterase inhibition by O,S-diethylphenylphosphonothioate.
AB - The inhibition kinetics and stereospecificity of the chiral nerve agent
derivative O,S-diethylphenylphosphonothioate (DEPP) were examined for two forms
of acetylcholinesterase (human and eel) and equine butyrylcholinesterase. Both S-
and R-DEPP are poor inhibitors of eel AChE (IC50 150MUM), consistent with a
large, nondiscriminatory binding interaction in the active site of this enzyme.
However, S-DEPP is active against human and equine AChE with low MUM IC50s. DEPP
stereospecificities (S/R) toward these enzymes are moderate (20) relative to
other cholinesterase-organophosphate (OP) systems. Pralidoxime, a common rescue
agent, affects a modest recovery of both hAChE and eqBChE from treatment with S
DEPP. This result is consistent with expected chemical modification by DEPP and
indicates that a measurable amount of the enzyme-phosphonate adduct does not
undergo aging. Kinetic analysis of inhibition of both hAChE and eqBChE by S-DEPP
yields KI values near 8MUM and k2 values of about 0.10min-1. In both cases, the
reaction is practically irreversible. Second order rate constants calculated from
these values are similar to those obtained previously using other thio
substituted OPs with bulky groups. Since BChE has a more accommodating acyl
pocket than AChE, the similar behaviors of both enzymes toward S-DEPP is notable
and is likely a reflection of the weakened potency of DEPP relative to chemical
warfare agents.
PMID- 28404521
TI - Diabetic complications in the cornea.
AB - Diabetic corneal alterations, such as delayed epithelial wound healing, edema,
recurrent erosions, neuropathy/loss of sensitivity, and tear film changes are
frequent but underdiagnosed complications of both type 1 (insulin-dependent) and
type 2 (non-insulin-dependent) diabetes mellitus. The disease affects corneal
epithelium, corneal nerves, tear film, and to a lesser extent, endothelium, and
also conjunctiva. These abnormalities may appear or become exacerbated following
trauma, as well as various surgeries including retinal, cataract or refractive.
The focus of the review is on mechanisms of diabetic corneal abnormalities,
available animal, tissue and organ culture models, and emerging treatments.
Changes of basement membrane structure and wound healing rates, the role of
various proteinases, advanced glycation end products (AGEs), abnormal growth and
motility factors (including opioid, epidermal, and hepatocyte growth factors) are
analyzed. Experimental therapeutics under development, including topical
naltrexone, insulin, inhibitors of aldose reductase, and AGEs, as well as
emerging gene and cell therapies are discussed in detail.
PMID- 28404527
TI - 'When you are homeless, you are not thinking about your medication, but your
food, shelter or heat for the night': behavioural determinants of homeless
patients' adherence to prescribed medicines.
AB - OBJECTIVES: This study aimed to explore behavioural determinants of homeless
patients' adherence to prescribed medicines using Theoretical Domains Framework
(TDF). STUDY DESIGN: A qualitative study using semi-structured, face-to-face
interviews. METHODS: Participants were recruited from a homelessness primary
healthcare centre in Aberdeen, United Kingdom (UK). Face-to-face interviews were
audio-recorded and transcribed verbatim. Thematic analysis of the interview data
was conducted using the Framework Approach based on the Theoretical Domains
Framework. National Health Service ethical and Research and Development (R&D)
approval was obtained. RESULTS: Twenty-five patients were interviewed, at which
point data saturation was achieved. A total of 13 out of 14 Theoretical Domains
Framework domains were identified that explained the determinants of adherence or
non-adherence to prescribed medicines. These included: 'beliefs about
consequences' (e.g. non-adherence leading to poor health); 'goals' of therapy
(e.g. being a 'normal' person with particular reference to methadone adherence);
and 'environmental context and resources' (e.g. stolen medicines and the lack of
secure storage). Obtaining food and shelter was higher priority than access and
adherence to prescribed medicines while being homeless. CONCLUSIONS: Behavioural
determinants of non-adherence identified in this study were mostly related to
participants' homelessness and associated lifestyle. Results are relevant to
developing behaviour change interventions targeting non-adherent homeless
patients and to the education of healthcare professionals serving this vulnerable
population.
PMID- 28404528
TI - Alcohol and healthy ageing: a challenge for alcohol policy.
AB - OBJECTIVES: This paper presents findings of a qualitative study of older people's
use of alcohol during retirement and identifies ways that an improved
understanding of older people's drinking can inform policy approaches to alcohol
and active and healthy ageing. STUDY DESIGN: Qualitative semi-structured
interviews conducted with a self-selecting sample of retired people. METHODS:
Participants were recruited from three geographical locations in the West of
Scotland. A quota sampling design was used to ensure a broad spread of
participants in terms of socio-economic position, age and gender. In total 40
participants were interviewed and the data analysed thematically using Braun and
Clarke's (2006) approach. RESULTS: Amongst those who used alcohol, it was most
often framed in terms of pleasure, relaxation, socialising and as a way to mark
the passage of time. Alcohol was often associated with social occasions and
interactions both in private and in public spaces. There were also many examples
of the use of imposed routines to limit alcohol use and of a decreasing volume of
alcohol being consumed as participants aged. This suggests that older people are
often active in constructing what they regard as 'healthier' routines around
alcohol use. However, processes and circumstances associated with ageing can lead
to risk of social isolation and/or increased alcohol consumption. Such processes
include retirement from paid work and other 'biographical disruptions' such as
caring for a partner, bereavement and/or loss of social networks. CONCLUSIONS:
These findings highlight processes that can result in changes in drinking habits
and routines. Whilst these processes can be associated with a reduction or
cessation of alcohol use as people age, they can also be associated with
increased risk of harmful alcohol consumption. Fractured or disrupted routines,
particularly those associated with bereavement or the burden of caring
responsibilities, through increasing the risk of loneliness and isolation, can
construct increased risk of harmful alcohol consumption. These findings reframe
the pathway of risk between ageing and alcohol-related harm by highlighting the
vulnerability to harmful drinking practices brought by fracture or sudden change
of routine. The findings point to a role for public health in supporting the
reconstruction of routines that provide structure and meaning and can be used to
actively manage the benefits and harms associated with drinking.
PMID- 28404529
TI - Cervical cancer, human papillomavirus and vaccines: assessment of the information
retrieved from general knowledge websites in Chile.
AB - OBJECTIVES: Cervical cancer is the most common gynaecologic malignancy worldwide
and is the sixth cause of cancer death in Chile. Human papillomavirus (HPV) is
responsible for most cervical cancers. Individuals seeking basic information
about HPV frequently turn to health information websites. We hypothesized that
some of their data may be inaccurate. STUDY DESIGN: Comparative analysis of
information. METHODS: We analyze the content of highly accessed websites such as
the Spanish version of Wikipedia and Yahoo Answers through the application of a
questionnaire, as well as a website managed by the Chilean Ministry of Health
(Minsal). The accuracy of each answer was confirmed by comparison with
information retrieved from articles published by indexed journals. RESULTS: The
information provided by the Spanish version of Wikipedia was accurate;
nevertheless a few omissions were detected. The quality of the information
provided by the Spanish version of Yahoo Answers was inaccurate and confusing.
The Minsal website lacked important information on several topics about HPV even
though it is managed and endorsed by the government. CONCLUSIONS: We suggest
periodical content reviews to increase the completeness, transparency and
correctness of the website.
PMID- 28404530
TI - Short-term effects of social encouragement on exercise behavior: insights from
China's Wanbu network.
AB - OBJECTIVES: The objective is to explore the short-term effects of social
encouragement on exercise behavior in China. STUDY DESIGN: A longitudinal
observational study. METHODS: We collected longitudinal data on exercise and
social interactions through public access to the Wanbu network, a large Chinese
social network designed to encourage people to walk more. Our data set consisted
of 5010 subjects who participated in the network between March 14, 2014, and
September 4, 2015, and had at least one social interaction recorded. The data
were analyzed using linear regression models relating the number of steps (NS)
walked per day to the number of comments (NC), number of thumbs-up (NT), and
number of posts (NP) received on the previous day, while adjusting for day of
week, quarter of year, and a fixed or random subject effect, with or without a
lag term (NS on the previous day) to account for serial correlation. RESULTS: We
found that all three social interactions have positive effects on the next day's
exercise level. The estimated effect sizes can be ordered as NT > NC > NP for
each of the four models considered. The results also indicate that the
participants walked less in the first quarter than in the other three quarters
and more on weekdays than on weekends, with Monday being the most active day of a
week. CONCLUSION: Social encouragement has positive short-term effects on
exercise behavior.
PMID- 28404531
TI - An integrated method of therapeutic lifestyle change for older adults with
dyslipidaemia.
AB - OBJECTIVES: To evaluate the effect of therapeutic lifestyle change with a non
pharmacological intervention method in older adults with dyslipidaemia. STUDY
DESIGN: Stratified randomized trial. METHODS: Participants with dyslipidaemia (n
= 214) aged >=60 years were randomized to the conventional guide group, the
educational course (EC) group, the telephone call (PC) group or the PC + EC group
for 24 weeks. Total cholesterol, triglyceride, low-density lipoprotein
cholesterol, high-density lipoprotein cholesterol and the knowledge, attitude and
practice score for serum lipids were measured at baseline (T1), mid-intervention
(week 12, T2) and post-intervention (week 24, T3). RESULTS: Except the
conventional guide group (n = 62), the PC group (n = 56), the EC group (n = 49)
and the PC + EC group (n = 47) showed significant intra-group differences in
serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, high
density lipoprotein cholesterol and knowledge, attitude and practice score after
the intervention. The improvements were most prominent and sustained over time in
the PC + EC group at post-intervention. CONCLUSIONS: The PC + EC method is more
efficient for improving serum lipids and enhancing health awareness than any
single programme in older adults with dyslipidaemia. This overlapped therapeutic
lifestyle change method may serve as a cost-effective adjunct and ensure the
continuity of high-quality health services for patients with dyslipidaemia.
PMID- 28404532
TI - Cost-effectiveness and cost utility of community screening for glaucoma in urban
India.
AB - OBJECTIVES: Population-based screening for glaucoma has been demonstrated to be
cost-effective if targeted at high-risk groups such as older adults and those
with a family history of glaucoma, and through use of a technician for conducting
initial assessment rather than a medical specialist. This study attempts to
investigate the cost-effectiveness of a hypothetical community screening and
subsequent treatment programme for glaucoma in comparison with current practice
(i.e. with no screening programme but with some opportunistic case finding) in
the urban areas of India. STUDY DESIGN: A hypothetical screening programme for
both primary open-angle glaucoma and angle-closure disease was built for a
population aged between 40 and 69 years in the urban areas of India. METHODS:
Screening and treatment costs were obtained from an administrator of a tertiary
eye hospital in India. The probabilities for the screening pathway were derived
from published literature and expert opinion. The glaucoma prevalence rates for
urban areas were adapted from the Chennai Glaucoma Study findings. A decision
analytical model using TreeAge Pro 2015 was built to model events, costs and
treatment pathways. One-way sensitivity analyses were conducted. RESULTS: The
introduction of a community screening programme for glaucoma is likely to be cost
effective, the estimated incremental cost-effectiveness ratio (ICER) values being
10,668.68 when compared with no screening programme and would treat an additional
4443 cases and prevent 1790 person-years of blindness over a 10-year period in
the urban areas of India. Sensitivity analyses revealed that glaucoma prevalence
rates across various age groups, screening uptake rate, follow-up compliance
after screening, treatment costs and utility values of health states associated
with medical and surgical treatment of glaucoma had an impact on the ICER values
of the screening programme. CONCLUSIONS: In comparison with current practice
(i.e. without a screening programme but with some opportunistic case finding),
the introduction of a community screening programme for glaucoma for the 40-69
years age group is likely to be relatively cost-effective if implemented in the
urban areas of India.
PMID- 28404533
TI - Costs of treatment of adult patients with cystic fibrosis in Poland and
internationally.
AB - OBJECTIVES: Despite its low prevalence, cystic fibrosis (CF) may have a
considerable impact on healthcare system expenditures in terms of direct
healthcare costs and lost productivity. This study was aimed at calculation of
costs associated with CF treatment in Poland, as well as at comparison of average
costs of treatment of CF patients in selected countries, taking into account the
purchasing power parity. STUDY DESIGN: Retrospective study. METHODS: The
researchers undertook a retrospective study of adult patients with CF taking into
account the broadest social perspective possible. Medical and non-medical direct
costs as well as indirect costs were calculated. CF costs estimated by
researchers from other countries over the last 15 years were also compared.
RESULTS: Total annual treatment cost per one CF patient in Poland was on average
EUR 19,581.08. Costs of treatment of CF patients over the last 15 years varied
between the countries and ranged from EUR 23,330.82 in Bulgaria to EUR 68,696.42
in the United States. CONCLUSIONS: CF is an international problem. The data in
this study could be the baseline for integrated and harmonised approaches for
periodical assessment of the future impact of new public policies and
interventions for rare diseases at the national and international levels.
PMID- 28404534
TI - Prevalence of female genital tuberculosis, its risk factors and associated
clinical features among the women of Andaman Islands, India: a community-based
study.
AB - OBJECTIVE: There is scarcity of information on the prevalence of female genital
tuberculosis (FGTB) in the community. The present study was carried out to
estimate the prevalence of FGTB, its risk factors and associated clinical
features. STUDY DESIGN: Community-based cross-sectional survey. METHODS: This
study was carried during October 2011 and May 2014 in the Andaman Islands. A
total of 13,300 women aged 20-59 years were primarily screened using a structured
questionnaire. About 721 (5.4%) were found initially eligible for screening for
genital tuberculosis by clinical examination and specimen collection for
laboratory tests but only 460 (63.8%) expressed their willingness. Endometrial
specimens were collected from 405 (88%) subjects. The association of the
potential risk factors with genital tuberculosis was tested by Chi-squared test.
A similar analysis was performed to identify clinical features associated with
genital tuberculosis. RESULTS: The estimated prevalence of FGTB was 45.1 cases
per 100,000 women (95% confidence interval [CI]: 16.6-98.1). Infertility and
oligomenorrhoea were identified as clinical features associated with FGTB. Past
history of tuberculosis and history of close contact with tuberculosis cases were
identified as risk factors. CONCLUSIONS: This study shows the prevalence of FGTB
among the female population of the Andaman Islands. Though the estimated
prevalence was close to the expected prevalence, but as only 63.8% of the
eligible women could be adequately screened, a much higher prevalence of FGTB
could not be ruled out. Infertility, oligomenorrhoea, past history of
tuberculosis and contact with tuberculosis case were identified as factors
associated with genital tuberculosis.
PMID- 28404535
TI - Vaccine wastage at the level of service delivery: a cross-sectional study.
PMID- 28404536
TI - Exploring the perceptions of pregnancy loss between two populations of South
Indian women: a pilot study.
PMID- 28404537
TI - Building a comprehensive syntactic and semantic corpus of Chinese clinical texts.
AB - OBJECTIVE: To build a comprehensive corpus covering syntactic and semantic
annotations of Chinese clinical texts with corresponding annotation guidelines
and methods as well as to develop tools trained on the annotated corpus, which
supplies baselines for research on Chinese texts in the clinical domain.
MATERIALS AND METHODS: An iterative annotation method was proposed to train
annotators and to develop annotation guidelines. Then, by using annotation
quality assurance measures, a comprehensive corpus was built, containing
annotations of part-of-speech (POS) tags, syntactic tags, entities, assertions,
and relations. Inter-annotator agreement (IAA) was calculated to evaluate the
annotation quality and a Chinese clinical text processing and information
extraction system (CCTPIES) was developed based on our annotated corpus. RESULTS:
The syntactic corpus consists of 138 Chinese clinical documents with 47,426
tokens and 2612 full parsing trees, while the semantic corpus includes 992
documents that annotated 39,511 entities with their assertions and 7693
relations. IAA evaluation shows that this comprehensive corpus is of good
quality, and the system modules are effective. DISCUSSION: The annotated corpus
makes a considerable contribution to natural language processing (NLP) research
into Chinese texts in the clinical domain. However, this corpus has a number of
limitations. Some additional types of clinical text should be introduced to
improve corpus coverage and active learning methods should be utilized to promote
annotation efficiency. CONCLUSIONS: In this study, several annotation guidelines
and an annotation method for Chinese clinical texts were proposed, and a
comprehensive corpus with its NLP modules were constructed, providing a
foundation for further study of applying NLP techniques to Chinese texts in the
clinical domain.
PMID- 28404538
TI - Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Patients in
the Black Sea Region of Turkey.
AB - Hematopoietic stem cell transplantation is a promising curative therapy for many
combined primary immunodeficiencies and phagocytic disorders. We retrospectively
reviewed pediatric cases of patients diagnosed with primary immunodeficiencies
and scheduled for hematopoietic stem cell transplantation. We identified 22
patients (median age, 6 months; age range, 1 month to 10 years) with various
diagnoses who received hematopoietic stem cell transplantation. The patient
diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi
syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency
(n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis
(n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22
patients, 7 received human leukocyte antigen-matched related hematopoietic stem
cell transplantation, 12 received haploidentical hematopoietic stem cell
transplantation, and 2 received matched unrelated hematopoietic stem cell
transplantation. The results showed that 5 patients had graft failure. Fourteen
patients survived, yielding an overall survival rate of 67%. Screening newborn
infants for primary immunodeficiency diseases may result in timely administration
of hematopoietic stem cell transplantation.
PMID- 28404539
TI - A National Registry of Thalassemia in Turkey: Demographic and Disease
Characteristics of Patients, Achievements, and Challenges in Prevention.
AB - OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National
Hemoglobinopathy Registry to demonstrate the demographic and disease
characteristics of patients and assess the efficacy of a hemoglobinopathy control
program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046
patients from 27 thalassemia centers were registered, of which 1988 were eligible
for analysis. This cohort mainly comprised patients with beta-thalassemia major
(n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients
were from the coastal areas of Turkey. The high number of patients in
Southeastern Anatolia was due to that area having the highest rates of
consanguineous marriage and fertility. The most common 11 mutations represented
90% of all beta-thalassemia alleles and 47% of those were IVS1-110(G->A)
mutations. The probability of undergoing splenectomy within the first 10 years of
life was 20%, a rate unchanged since the 1980s. Iron chelators were administered
as monotherapy regimens in 95% of patients and deferasirox was prescribed in
81.3% of those cases. Deferasirox administration was the highest (93.6%) in
patients aged <10 years. Of the thalassemia major patients, 5.8% had match
related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac
disease was detected as a major cause of death and did not show a decreasing
trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been
implemented since 2003, the affected births have shown a consistent decrease only
after 2009, being at lowest 34 cases per year. This program failure resulted from
a lack of premarital screening in the majority of cases. Additional problems were
unawareness of the risk and misinformation of the at-risk couples. In addition,
prenatal diagnosis was either not offered to or was not accepted by the at-risk
families. This study indicated that a continuous effort is needed for optimizing
the management of thalassemia and the development of strategies is essential for
further achievements in the HCP in Turkey.
PMID- 28404540
TI - Abnormal mRNA Expression Levels of Telomere-Binding Proteins Represent Biomarkers
in Myelodysplastic Syndromes: A Case-Control Study.
AB - OBJECTIVE: As evidence was shown that abnormal shortening of telomeres begins to
accumulate in myelodysplastic syndrome (MDS) patients, this study was conducted
to determine the relationship between the mRNA expression levels of telomere
binding proteins (TRF1/TRF2/TIN2/TPP1/POT1/RAP1) and the risk level in MDS.
MATERIALS AND METHODS: There were 40 patients with MDS and 40 normal controls in
this study. Methods including telomere content assays and quantitative reverse
transcription-polymerase chain reaction were used to examine the mRNA levels of
TRF1/TRF2/TIN2/TPP1/POT1/RAP1 in patients with MDS. RESULTS: Compared to the
normal group used as a control, the mRNA expression levels of RAP1/POT1/TPP1 of
the patients with MDS were decreased, whereas their levels of TRF1/TRF2 and TIN2
were increased. A positive correlation was found between the TRF1, TRF2, and TIN2
mRNA expression levels and the risk level of the International Prognostic Scoring
System (IPSS) and the World Health Organization Prognostic Scoring System (WPSS)
criteria; however, a negative correlation was found between RAP1/POT1/TPP1 mRNA
expression levels and the risk levels of IPSS and WPSS criteria. CONCLUSION:
Because the reduction of TRF1/TRF2/TIN2 mRNA expression and the increase of
RAP1/POT1/TPP1 mRNA expression are closely related to the risk levels of the IPSS
and WPSS criteria in MDS, it is thought that these telomere-binding proteins
could lead to abnormal telomere length and function, which cause chromosomal
abnormalities in MDS. With this evidence, we suggest that those proteins' mRNA
expressions could be used as biomarkers for the assessment of the risk degree of
MDS patients.
PMID- 28404541
TI - Making Air Pollution Visible: A Tool for Promoting Environmental Health Literacy.
AB - BACKGROUND: Digital maps are instrumental in conveying information about
environmental hazards geographically. For laypersons, computer-based maps can
serve as tools to promote environmental health literacy about invisible traffic
related air pollution and ultrafine particles. Concentrations of these pollutants
are higher near major roadways and increasingly linked to adverse health effects.
Interactive computer maps provide visualizations that can allow users to build
mental models of the spatial distribution of ultrafine particles in a community
and learn about the risk of exposure in a geographic context. OBJECTIVE: The
objective of this work was to develop a new software tool appropriate for
educating members of the Boston Chinatown community (Boston, MA, USA) about the
nature and potential health risks of traffic-related air pollution. The tool, the
Interactive Map of Chinatown Traffic Pollution ("Air Pollution Map" hereafter),
is a prototype that can be adapted for the purpose of educating community members
across a range of socioeconomic contexts. METHODS: We built the educational
visualization tool on the open source Weave software platform. We designed the
tool as the centerpiece of a multimodal and intergenerational educational
intervention about the health risk of traffic-related air pollution. We used a
previously published fine resolution (20 m) hourly land-use regression model of
ultrafine particles as the algorithm for predicting pollution levels and applied
it to one neighborhood, Boston Chinatown. In designing the map, we consulted
community experts to help customize the user interface to communication styles
prevalent in the target community. RESULTS: The product is a map that displays
ultrafine particulate concentrations averaged across census blocks using a color
gradation from white to dark red. The interactive features allow users to explore
and learn how changing meteorological conditions and traffic volume influence
ultrafine particle concentrations. Users can also select from multiple map
layers, such as a street map or satellite view. The map legends and labels are
available in both Chinese and English, and are thus accessible to immigrants and
residents with proficiency in either language. The map can be either Web or
desktop based. CONCLUSIONS: The Air Pollution Map incorporates relevant language
and landmarks to make complex scientific information about ultrafine particles
accessible to members of the Boston Chinatown community. In future work, we will
test the map in an educational intervention that features intergenerational
colearning and the use of supplementary multimedia presentations.
PMID- 28404543
TI - What's the point of happiness research?
PMID- 28404542
TI - Immediate Mood Scaler: Tracking Symptoms of Depression and Anxiety Using a Novel
Mobile Mood Scale.
AB - BACKGROUND: Mood disorders are dynamic disorders characterized by multimodal
symptoms. Clinical assessment of symptoms is currently limited to relatively
sparse, routine clinic visits, requiring retrospective recollection of symptoms
present in the weeks preceding the visit. Novel advances in mobile tools now
support ecological momentary assessment of mood, conducted frequently using
mobile devices, outside the clinical setting. Such mood assessment may help
circumvent problems associated with infrequent reporting and better characterize
the dynamic presentation of mood symptoms, informing the delivery of novel
treatment options. OBJECTIVES: The aim of our study was to validate the Immediate
Mood Scaler (IMS), a newly developed, iPad-deliverable 22-item self-report tool
designed to capture current mood states. METHODS: A total of 110 individuals
completed standardized questionnaires (Patient Health Questionnaire, 9-item [PHQ
9]; generalized anxiety disorder, 7-Item [GAD-7]; and rumination scale) and IMS
at baseline. Of the total, 56 completed at least one additional session of IMS,
and 17 completed one additional administration of PHQ-9 and GAD-7. We conducted
exploratory Principal Axis Factor Analysis to assess dimensionality of IMS, and
computed zero-order correlations to investigate associations between IMS and
standardized scales. Linear Mixed Model (LMM) was used to assess IMS stability
across time and to test predictability of PHQ-9 and GAD-7 score by IMS. RESULTS:
Strong correlations were found between standard mood scales and the IMS at
baseline (r=.57-.59, P<.001). A factor analysis revealed a 12-item IMS ("IMS-12")
with two factors: a "depression" factor and an "anxiety" factor. IMS-12
depression subscale was more strongly correlated with PHQ-9 than with GAD-7
(z=1.88, P=.03), but the reverse pattern was not found for IMS-12 anxiety
subscale. IMS-12 showed less stability over time compared with PHQ-9 and GAD-7
(.65 vs .91), potentially reflecting more sensitivity to mood dynamics. In
addition, IMS-12 ratings indicated that individuals with mild to moderate
depression had greater mood fluctuations compared with individuals with severe
depression (.42 vs .79; P=.04). Finally, IMS-12 significantly contributed to the
prediction of subsequent PHQ-9 (beta=1.03, P=.02) and GAD-7 scores (beta =.93,
P=.01). CONCLUSIONS: Collectively, these data suggest that the 12-item IMS (IMS
12) is a valid tool to assess momentary mood symptoms related to anxiety and
depression. Although IMS-12 shows good correlation with standardized scales, it
further captures mood fluctuations better and significantly adds to the
prediction of the scales. Results are discussed in the context of providing
continuous symptom quantification that may inform novel treatment options and
support personalized treatment plans.
PMID- 28404545
TI - Doxepin inhibits GPVI-dependent platelet Ca2+ signaling and collagen-dependent
thrombus formation.
AB - Platelet adhesion, activation, and aggregation are essential for primary
hemostasis, but are also critically involved in the development of acute arterial
thrombotic occlusion. Stimulation of the collagen receptor glycoprotein VI (GPVI)
leads to phospholipase Cgamma2-dependent inositol triphosphate (IP3) production
with subsequent platelet activation, due to increased intracellular Ca2+
concentration ([Ca2+]i). Although tricyclic antidepressants have been shown to
potentially impair platelet activation, nothing is hitherto known about potential
effects of the tricyclic antidepressant doxepin on platelet Ca2+ signaling and
thrombus formation. As shown in the present study, doxepin significantly
diminished the stimulatory effect of GPVI agonist collagen-related peptide (CRP)
on intracellular Ca2+ release as well as subsequent extracellular Ca2+ influx.
Doxepin was partially effective by impairment of CRP-dependent IP3 production.
Moreover, doxepin abrogated CRP-induced platelet degranulation and integrin
alphaIIbbeta3 activation and aggregation. Finally, doxepin markedly blunted in
vitro platelet adhesion to collagen and thrombus formation under high arterial
shear rates (1,700-s). In conclusion, doxepin is a powerful inhibitor of GPVI
dependent platelet Ca2+ signaling, platelet activation, and thrombus formation.
PMID- 28404547
TI - The role of miR-320a and IL-1beta in human chondrocyte degradation.
AB - OBJECTIVES: This study aimed to explore the role of miR-320a in the pathogenesis
of osteoarthritis (OA). METHODS: Human cartilage cells (C28/I2) were transfected
with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL
1beta. Subsequently the expression of collagen type II alpha 1 (Col2alpha1) and
aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and
matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay,
qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia
Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co
transfected with miR-320a and PBX3 expressing vector, or cells were transfected
with miR-320a and treated with a nuclear factor kappa B (NF-kappaB) antagonist
MG132. The changes in Col2alpha1 and ACAN expression, and in sGAG and MMP-13
concentrations, were measured again. Statistical comparisons were made between
two groups by using the two-tailed paired t-test. RESULTS: Expression of miR-320a
was elevated in OA cartilage tissues and chondrocytes, and in IL-1beta-stimulated
C28/I2 cells (p < 0.05 or p < 0.01). MiR-320a overexpression enhanced IL-1beta
induced down-regulation of Col2alpha1 and ACAN and sGAG, and increased the IL
1beta-induced overexpression of MMP-13 (p < 0.01). PBX3 was a direct target of
miR-320a. PBX3 and MG132 co-transfection attenuated the effects of miR-320a on
the expression of Col2alpha1, ACAN, sGAG and MMP-13(p < 0.01). CONCLUSION:
Overexpression of miR-320a might enhance IL-1beta-induced cartilage degradation
factors. These effects might be via targeting PBX3 and regulating NF-kappaB.Cite
this article: Y. Jin, X. Chen, Z. Y. Gao, K. Liu, Y. Hou, J. Zheng. The role of
miR-320a and IL-1beta in human chondrocyte degradation. Bone Joint Res 2017;6:
203. DOI: 10.1302/2046-3758.64.BJR-2016-0224.R1.
PMID- 28404548
TI - The tip-apex distance in the X-Bolt dynamic plating system.
AB - OBJECTIVES: The Sliding Hip Screw (SHS) is commonly used to treat trochanteric
hip fractures. Fixation failure is a devastating complication requiring complex
revision surgery. One mode of fixation failure is lag screw cut-out which is
greatest in unstable fracture patterns and when the tip-apex distance of the lag
screw is > 25 mm. The X-Bolt Dynamic Hip Plating System (X-Bolt Orthopaedics,
Dublin, Ireland) is a new device which aims to reduce this risk of cut-out.
However, some surgeons have reported difficulty minimising the tip-apex distance
with subsequent concerns that this may lead to an increased risk of cut-out.
PATIENTS AND METHODS: We measured the tip-apex distance from the intra-operative
radiographs of 93 unstable trochanteric hip fractures enrolled in a randomised
controlled trial (Warwick Hip Trauma Evaluation, WHiTE One trial). Participants
were treated with either the sliding hip screw or the X-Bolt dynamic hip plating
system. We also recorded the incidence of cut-out in both groups, at a median
follow-up time of 17 months. RESULTS: There was a significantly increased tip
apex distance with the use of the X-Bolt (mean difference 3.7mm (95% confidence
interval 1.58 to 5.73); SHS mean 17.1 mm, X-Bolt mean 20.8; p = 0.001. However,
this was not associated with an increased incidence of cut-out at a median follow
up time of 17 months, with three cut-outs (6%) in the SHS group and 0 (0%) in the
X-Bolt group. CONCLUSION: The X-Bolt is a safe implant with no increased risk for
cut-out. Concerns about minimising the tip-apex distance may be justified but do
not appear to be clinically important.Cite this article: M. A. Fernandez, A.
Aquilina, J. Achten, N. Parsons, M. L. Costa, X. L. Griffin. The tip-apex
distance in the X-Bolt dynamic plating system. Bone Joint Res 2017;6:-207. DOI:
10.1302/2046-3758.64.BJR-2015-0016.R2.
PMID- 28404549
TI - Doctors can withdraw life support from baby with rare genetic disorder, says
judge.
PMID- 28404550
TI - Pelvic gossypiboma with spontaneous intravesical erosion.
AB - A 23-year-old man presented with chronic lower urinary tract symptoms and right
flank pain. He had undergone ureterolithotomy a few years ago. Ultrasonography
and CT of the abdomen and pelvis showed a right paravesical mass and proximal
hydroureteronephrosis. Cystoscopic examination revealed a part of surgical gauze
embedded in the right lateral wall of the bladder. The surgical gauze was
completely retrieved with grasping forceps without any additional procedures. The
patient experienced prompt relief of his symptoms and at follow-up, imaging
studies revealed resolution of the pelvic mass and non-obstructed clearance of
right-side collecting system. Pelvic gossypiboma with partial intravesical
erosion is an unusual presentation and can be managed successfully by cystoscopic
manipulation.
PMID- 28404551
TI - Endocervical gastric-type adenocarcinoma, an unrelated HPV tumour: difficulties
in screening and diagnosis.
AB - Gastric-type adenocarcinoma of the cervix (GAS) is an uncommon and aggressive
tumour unrelated to human papillomavirus (HPV) infection with distinctive
histological and immunohistochemical characteristics. GAS may be associated with
lobular endocervical glandular hyperplasia (LEGH), another unusual lesion. We
report a case of a 59-year-old woman with screening cytology 'AGC-Neo' and
cervical conisation exhibiting cervical intraepithelial neoplasia grade 1,
extensive LEGH and canal sampling with abundant mucinous cells. Based on the
possible association between LEGH and GAS, a total hysterectomy was performed.
The histological diagnosis revealed a morphological gradient of lesions: LEGH,
minimal deviation adenocarcinoma and GAS with lymphatic invasion.
Immunohistochemistry revealed strong MUC6 expression and no p16 staining. After
pelvic radiotherapy, the patient continues follow-up evaluation. The diagnostic
difficulties of GAS and its relationship with LEGH are discussed. This rare
tumour is important because it is poorly symptomatic and potentially aggressive.
In addition, the methods for cancer control related to HPV do not affect this
tumour.
PMID- 28404552
TI - Priority setting in paediatric preventive care research.
AB - OBJECTIVES: To identify the unanswered research questions in paediatric
preventive care that are most important to parents and clinicians, and to explore
how questions from parents and clinicians may differ. DESIGN: Iterative mixed
methods research priority setting process. SETTING: Toronto, Ontario, Canada.
PARTICIPANTS: Parents of children aged 0-5 years enrolled in a research network
in Toronto, and clinicians practising in Toronto, Ontario, Canada. INTERVENTIONS:
Informed by the James Lind Alliance's methodology, an online questionnaire
collected unanswered research questions in paediatric preventive care from study
participants. Similar submissions were combined and ranked. A consensus workshop
attended by 28 parents and clinicians considered the most highly ranked
submissions and used the nominal group technique to select the 10 most important
unanswered research questions. RESULTS: Forty-two clinicians and 115 parents
submitted 255 and 791 research questions, respectively, which were combined into
79 indicative questions. Most submissions were about nutrition, illness
prevention, parenting and behaviour management. Parents were more likely to ask
questions about screen time (49 parents vs 8 clinicians, p<0.05) and
environmental toxins (18 parents vs 0 clinicians, p<0.05). The top 10 unanswered
questions identified at the workshop related to mental health, parental stress,
physical activity, obesity, childhood development, behaviour management and
screen time. CONCLUSION: The top 10 most important unanswered research questions
in paediatric preventive care from the perspective of parents and clinicians were
identified. These research priorities may be important in advancing preventive
healthcare for children.
PMID- 28404553
TI - Airway emergencies presenting to the paediatric emergency department requiring
advanced management techniques.
AB - BACKGROUND: Airway emergencies presenting to the emergency department (ED) are
usually managed with conventional equipment and techniques. The patient group
managed urgently in the operating room (OR) has not been described. AIMS: This
study aims to describe a case series of children presenting to the ED with airway
emergencies managed urgently in the OR, particularly the anaesthetic equipment
and techniques used and airway findings. METHODS: A retrospective cohort study
undertaken at The Royal Children's Hospital, Melbourne, Australia. All patients
presenting to the ED between 1 January 2012 and 30 July 2015 (42 months) with an
airway emergency who were subsequently managed in the OR were included. Patient
characteristics, anaesthetic equipment and technique and airway findings were
recorded. RESULTS: Twenty-two airway emergencies in 21 patients were included
over the study period, on average one every 2 months. Median age was 18 months
and 43% were male. Inhalational induction was used in 77.3%, combined
inhalational and intravenous induction in 9.1%, and intravenous induction alone
in 13.6%. The most commonly used inhalational induction agent was sevoflurane,
and the most commonly used intravenous induction agents were ketamine and
propofol. Ten airway emergencies did not require intubation, seven for removal of
inhaled foreign body, two with progressive tracheal stenosis requiring emergent
dilatation and one examination under anaesthesia to rule out inhaled foreign
body. Of the 12 airway emergencies that required immediate intubation, direct
laryngoscopy was used in 9 and fibre-optic intubating bronchoscopy in 3. For
intubations performed by direct laryngoscopy, one was difficult (Cormack and
Lehane grade 3). First pass success was 83.3%. Adverse events occurred in 3/22
(13.6%) cases. CONCLUSION: Advanced airway techniques, including inhalational
induction and intubation via fibre-optic intubating bronchoscope, are rarely but
predictably required in the management of patients presenting to the ED.
Institutions caring for children should prepare in advance where such patients
should be managed, by whom, and provide equipment and training for their care.
PMID- 28404555
TI - Simi Move: entry level mobile app to analyse walking and running gait.
PMID- 28404554
TI - Oesophageal eosinophilia in children with coeliac disease.
AB - OBJECTIVES: An association between coeliac disease (CD) and eosinophilic
oesophagitis (EoE)/oesophageal eosinophilia (EE) has been suggested. We sought to
characterise children with CD+EE in-depth and assess the contribution of each
condition to the clinical presentation and treatment response. STUDY DESIGN:
Medical records of children with both CD+EE, or isolated EoE diagnosed between
2000 and 2014, were retrospectively reviewed and compared with patients with
isolated CD or epigastric pain. Frequency of EE was calculated from endoscopy
results of patients with suspected CD or epigastric pain between 2011 and 2014.
Missing data were obtained via a telephone questionnaire. SETTING: Single large,
tertiary paediatric centre. PATIENTS: 17 CD+EE, 46 EoE, 302 isolated CD and 247
epigastric pain. RESULTS: The patients with CD+EE shared characteristics of both
individual conditions. While age at diagnosis, family history of autoimmunity/CD
and anaemia were similar to patients with CD, other characteristics such as male
gender, personal/family history of atopy, peripheral eosinophilia and oesophageal
white papules were more similar to patients with EoE. Combined patients (CD+EE)
tended to present with CD-associated symptoms; the majority (63%) later developed
typical EoE symptoms. Only a minority (21%) of combined patients had EE that
resolved after a gluten-free diet; another 21% had normalisation of EE upon
proton pump inhibitor treatment. The remainder required EoE-specific treatment.
CONCLUSION: Patients with CD found to have EE share characteristics with both
isolated CD and EoE. It appears that these are two coexisting entities presenting
in the same patient rather than eosinophilia associated with CD, and therefore,
interventions separately addressing each condition may be considered.
PMID- 28404556
TI - Recent acute prerace systemic illness in runners increases the risk of not
finishing the race: SAFER study V.
AB - AIM: There are limited data on the negative effects of exercise in athletes with
acute infective illness. The aim of this study was to determine whether a
recently diagnosed prerace acute illness in runners affects the ability to finish
a race. METHODS: Runners were prospectively evaluated in the 3 days before the
race for acute infective illness and then received participation advice using
clinical criteria based on systemic or localised symptoms/signs. We compared the
did-not-start and the did-not-finish frequencies of ill runners (Ill=172:
localised=58.7%; systemic=41.3%) with that of a control group of runners (Con=53
734). RESULTS: Runners with a systemic illness were 10.4% more likely not to
start compared with controls (29.6% vs 19.2%) (p=0.0073). The risk difference of
not starting the race in runners who were advised not to run the race compared
with controls was 37.3% (56.5% vs 19.2%, p<0.0001). Compared with controls,
runners with illness had a significantly (p<0.05) greater risk (any illness (5.2%
vs 1.6%), systemic illness (8.0% vs 1.6%), illness <24 hours before the race
(11.1% vs 1.6%)) and relative risk (prevalence risk ratio) (any illness=3.4,
systemic illness=4.9, systemic illness <24 hours before the race=7.0) of not
finishing the race. CONCLUSIONS: Runners with prerace acute systemic illness, and
particularly those diagnosed <24 hours before race day, are less likely to finish
the race, indicating a reduction in race performance.
PMID- 28404557
TI - Exercise prescription for overhead athletes with shoulder pathology: a systematic
review with best evidence synthesis.
AB - OBJECTIVE: To produce a best evidence synthesis of exercise prescription used
when treating shoulder pathology in the overhead athlete. DESIGN: A systematic
review of exercises used in overhead athletes including case studies and clinical
commentaries. DATA SOURCES: MEDLINE, PubMed, SPORTDiscus and CINAHL from database
inception through July 8, 2016. METHODS: We examined data from randomised
controlled trials and prospective cohort (level I-IV evidence) studies that
addressed exercise intervention in the rehabilitation of the overhead athlete
with shoulder pathology. Case studies and clinical commentaries (level V
evidence) were examined to account for expert opinion-based research. Data were
combined using best evidence synthesis and graded (A-F) recommendations (Centre
for Evidence-Based Medicine). RESULTS: There were 33 unique exercises in six
level I-IV studies that met our inclusion criteria. Most exercises were single
plane, upper extremity exercises performed below 90o of elevation. There were 102
unique exercises in 33 level V studies that met our inclusion criteria. These
exercises emphasised plyometrics, kinetic chain and sport-specific training.
CONCLUSIONS AND RELEVANCE: Overall, evidence for exercise interventions in
overhead athletes with shoulder pathology is dominated by expert opinion (grade
D). There is great variability between exercise approaches suggested by experts
and those investigated in research studies and the overall level of evidence is
low. The strongest available evidence (level B) supports the use of single-plane,
open chain upper extremity exercises performed below 90 degrees of elevation and
closed chain upper extremity exercises. Clinical expert pieces support a more
advanced, global treatment approach consistent with the complex, multidimensional
nature of sport.
PMID- 28404558
TI - Factors associated with participation in resistance training: a systematic
review.
AB - OBJECTIVE: Regular participation in resistance training (RT) is critical to
health and recommended in most international physical activity guidelines. Few
people, however, participate in RT. The purpose of this review was to assess the
demographic, behavioural, intrapersonal, interpersonal and environmental factors
associated with participating in RT. DATA SOURCES: Eligible studies were from
English peer-reviewed published articles that examined correlates or determinants
of RT in adult samples. Searches were performed from August 2015 to April 2016 in
six databases. RESULTS: We identified 51 independent data sets, from nine
countries, primarily of moderate to high quality, and 23 factors related to
participating in RT. Education, perceived health status, quality of life,
affective judgements, self-efficacy, intention, self-regulation behaviours,
subjective norm and programme leadership were associated with RT. CONCLUSION: Low
education levels and poor health status were associated with low participation
rates in RT. Intrapersonal factors including affective judgements, self-efficacy,
and self-regulation behaviours, and interpersonal factors including subjective
norms and programme leadership may be important for promoting RT behaviours.
PMID- 28404559
TI - Surviving murine experimental sepsis affects the function and morphology of the
inner ear.
AB - Severe sepsis is known to result in various neurological long-term deficits in
human. Recently, a link between severe, lethal sepsis and significant hearing
loss with correlating histomorphological inner ear changes in mice (C57BL/6) was
observed. However, if similar observations can be made in severe, non-lethal
sepsis in mice is unclear. This study evaluates mice after severe, non-lethal
sepsis for analogue functional and histomorphological alterations of the inner
ear.A total of 63 C57BL/6 mice were included in the study. All underwent an
initial hearing test with auditory brainstem response on day 1. In 35 mice sepsis
was induced by cecal ligation and puncture (CLP), in 15 sham surgery was
performed and 13 served as healthy control. A second hearing test was performed
on day 7. All mice were sacrificed afterwards for further histomorphological
evaluation of the inner ears. Immunohistochemical analysis with apoptotic markers
Cleaved-caspase 3, BAX and BCL-2 were performed to identify structural inner ear
damage.Of all CLP mice, 21/35 (60.0%) died due to the induced sepsis. Of the
surviving CLP mice, 14/35 (40.0%), post-treatment hearing thresholds differed
significantly from the sham and control mice (P<0.001). Positive immunostaining
at different inner ear structures, like the spiral ligament or the supporting
cells could be observed. The percentage of the immunostained positive area in the
spiral ligament significantly correlated with the grade of hearing loss for BAX
(P=0.027) and Cleaved-caspase 3 (P=0.024) but not for BCL 2 (P>0.05).The present
data suggests that severe, non-lethal sepsis in mice results in significantly
elevated hearing thresholds. A positive labelling for the pro-apoptotic markers
BAX and Cleaved-caspase 3 suggested the induction of apoptosis in inner ear.
PMID- 28404561
TI - Electrical injury.
PMID- 28404562
TI - An important cause of erythroderma.
PMID- 28404560
TI - Statin Eligibility and Outpatient Care Prior to ST-Segment Elevation Myocardial
Infarction.
AB - BACKGROUND: The impact of the 2013 American College of Cardiology/American Heart
Association cholesterol guidelines on statin eligibility in individuals otherwise
destined to experience cardiovascular disease (CVD) events is unclear. METHODS
AND RESULTS: We analyzed a prospective cohort of consecutive ST-segment elevation
myocardial infarction (STEMI) patients from a regional STEMI system with data on
patient demographics, low-density lipoprotein cholesterol levels, CVD risk
factors, medication use, and outpatient visits over the 2 years prior to STEMI.
We determined pre-STEMI eligibility according to American College of
Cardiology/American Heart Association guidelines and the prior Third Report of
the Adult Treatment Panel guidelines. Our sample included 1062 patients with a
mean age of 63.7 (13.0) years (72.5% male), and 761 (71.7%) did not have known
CVD prior to STEMI. Only 62.5% and 19.3% of individuals with and without prior
CVD were taking a statin before STEMI, respectively. In individuals not taking a
statin, median (interquartile range) low-density lipoprotein cholesterol levels
in those with and without known CVD were low (108 [83, 138] mg/dL and 110 [87,
133] mg/dL). For individuals not taking a statin, only 38.7% were statin eligible
by ATP III guidelines. Conversely, 79.0% would have been statin eligible
according to American College of Cardiology/American Heart Association
guidelines. Less than half of individuals with (49.2%) and without (41.1%) prior
CVD had seen a primary care provider during the 2 years prior to STEMI.
CONCLUSIONS: In a large cohort of STEMI patients, application of American College
of Cardiology/American Heart Association guidelines more than doubled pre-STEMI
statin eligibility compared with Third Report of the Adult Treatment Panel
guidelines. However, access to and utilization of health care, a necessity for
guideline implementation, was suboptimal prior to STEMI.
PMID- 28404563
TI - Haemorrhagic cholecystitis in a newly anticoagulated patient.
AB - A 74-year-old man undergoing rehabilitation after pneumonia developed right upper
quadrant abdominal pain. Five days earlier he had been commenced on apixaban for
a new diagnosis of atrial fibrillation. Ultrasound and CT scans revealed an
acalculous grossly thickened gallbladder, with high attenuation non-echogenic
material both within and surrounding the structure. Active contrast extravasation
was seen at the neck. On laparotomy, a perforated internally bleeding gallbladder
containing a single calculus was found, with significant free blood within the
abdomen. After cholecystectomy, the patient recovered slowly in hospital before
nursing home placement.
PMID- 28404564
TI - Truth will out: a rare case of amyloid cardiomyopathy.
PMID- 28404565
TI - WHO condemns suspected use of chemical weapons.
PMID- 28404566
TI - National approach to OTC prescribing is needed.
PMID- 28404567
TI - Accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy.
AB - Hydroxychloroquine is an oral antimalarial medication commonly used off-label for
a variety of rheumatological conditions, including systemic lupus erythematosus,
rheumatoid arthritis, Sjogren's syndrome and dermatomyositis. We present a case
of a 64-year-old woman who presented with acute onset headache, bilateral
tinnitus, and left-sided facial numbness and tingling in the setting of
accidentally overdosing on hydroxychloroquine. By the next morning, the patient
began to experience worsening in the tingling sensation and it eventually spread
to her left arm, thigh and distal extremities. The patient also complained of new
onset blurring of her peripheral vision and feeling 'off balance.' Despite a
complete neurological and ophthalmological work-up with unremarkable imaging and
blood work, the patient has had no improvement in her tinnitus, left-sided
paresthesias, visual disturbance or ataxia. This is a unique case of
hydroxychloroquine overdose resulting in permanent neurotoxic vestibulopathy.
PMID- 28404569
TI - Analysis Suggests Wider Use for PARP Inhibitors.
AB - Researchers have developed a new tool, HRDetect, to pinpoint tumors that display
BRCA deficiency but don't harbor BRCA1/2 mutations. Evaluating their method in
breast, ovarian, and pancreatic cancers, they identified patients whose tumors
were potentially vulnerable to PARP inhibition but who didn't carry these
mutations.
PMID- 28404570
TI - Three design aspects for high quality post-marketing cohort studies.
PMID- 28404572
TI - An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in
Rhesus Macaques.
AB - A goal for HIV prevention programs is to develop safe, effective vaccines that
elicit durable and broadly protective antibodies. Many vaccine programs focus on
the immune responses to critical epitopes in the gp120 portion of HIV envelope
glycoprotein (Env) and seek to improve the quality and quantity of antibodies by
altering the sequence, conformation, oligomerization, or glycosylation of gp120
to activate appropriate germ line B cells and mimic the subsequent maturation
pathways seen in infected individuals. As a complement to these strategies, we
developed dimeric fusion protein immunogens consisting of HIVBaL gp120 monomer
attached to a Gly/Ser linker that is, in turn, fused to one half of the dimeric
Fc domain from rhesus macaque IgG1 (Env-rFc). We envisioned that Env-rFc may
mimic some aspects of immune complexes by binding Fc gamma receptors (FcgammaRs)
on immune cells to increase the strength, breadth, and durability of Env-specific
antibody responses. The Env-rFc retained a capacity to bind both cell surface CD4
and FcgammaRs. In a rhesus macaque immunization study, Env-rFc elicited higher
gp120 binding antibody titers than Env and elicited antibodies that recognize CD4
induced epitopes. Env-rFc also induced antibodies capable of neutralizing tier 1A
HIV pseudotyped viruses and mediating antibody-dependent cellular cytotoxicity,
outcomes not observed with monomeric gp120 in our study. Serum antibodies
produced in Env-rFc-immunized macaques had increased durability compared to that
of Env monomer immunization. Our work suggests that adding IgG1 Fc to Env-based
immunogens may stimulate increased effector capacity in the immune sera and
improve the protective serum antibody response.
PMID- 28404571
TI - Early Detection of Circulating Antigen and IgM-Associated Immune Complexes during
Experimental Mycobacterium bovis Infection in Cattle.
AB - The presence of circulating antigen in cattle experimentally infected with
Mycobacterium bovis was demonstrated using dual-path platform (DPP) technology.
The antigen capture immunoassays employed rabbit polyclonal antibody recognizing
predominantly M. tuberculosis complex-specific epitopes and were able to detect
soluble substances and whole cells of mycobacteria. The antigen found in serum
appeared to be mostly bound to IgM, but not to IgG, within the immune complexes
formed at early stages of M. bovis infection. The antigen was also detected in
bile and urine, indicating possible clearance pathways. The data correlation
analyses supported the idea of the role of IgM responses in antigen persistence
during M. bovis infection. The antigen was detectable in serum months prior to
detectable antibody seroconversion. This proof-of-concept study suggested the
potential for improved immunodiagnostics for bovine tuberculosis.
PMID- 28404573
TI - Cytomegalovirus Virions Shed in Urine Have a Reversible Block to Epithelial Cell
Entry and Are Highly Resistant to Antibody Neutralization.
AB - Cytomegalovirus (CMV) causes sensorineural hearing loss and developmental
disabilities in newborns when infections are acquired in utero Pregnant women may
acquire CMV from oral exposure to CMV in urine or saliva from young children.
Neutralizing antibodies in maternal saliva have the potential to prevent maternal
infection and, in turn, fetal infection. As CMV uses different viral glycoprotein
complexes to enter different cell types, the first cells to be infected in the
oral cavity could determine the type of antibodies needed to disrupt oral
transmission. Antibodies targeting the pentameric complex (PC) should block CMV
entry into epithelial cells but not into fibroblasts or Langerhans cells (which
do not require the PC for entry), while antibodies targeting glycoprotein
complexes gB or gH/gL would be needed to block entry into fibroblasts, Langerhans
cells, or other cell types. To assess the potential for antibodies to disrupt
oral acquisition, CMV from culture-positive urine samples (uCMV) was used to
study cell tropisms and sensitivity to antibody neutralization. uCMV entered
epithelial cells poorly compared with the entry into fibroblasts. CMV-hyperimmune
globulin or monoclonal antibodies targeting gB, gH/gL, or the PC were incapable
of blocking the entry of uCMV into either fibroblasts or epithelial cells. Both
phenotypes were lost after one passage in cultured fibroblasts, suggestive of a
nongenetic mechanism. These results suggest that uCMV virions have a reversible
block to epithelial cell entry. Antibodies may be ineffective in preventing
maternal oral CMV acquisition but may limit viral spread in blood or tissues,
thereby reducing or preventing fetal infection and disease.
PMID- 28404574
TI - Parasitic Infections in Pregnancy Decrease Placental Transfer of Antipneumococcus
Antibodies.
AB - Many factors can influence maternal placental antibody transfer to the fetus,
which confers important immune protection to the newborn infant. However, little
is known about the effect of maternal parasitic infection on placental antibody
transfer. To investigate this, we selected from a parent study of 576 pregnant
Kenyan women four groups of women with term deliveries (>=37 weeks), including
uninfected women (n = 30) and women with solo infections with malaria (n = 30),
hookworm (n = 30), or schistosomiasis (n = 10). Maternal plasma at delivery and
infant cord blood were tested via multiplex fluorescent bead assay for IgG
against 10 pneumococcal serotypes (PnPs 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and
23F), diphtheria toxoid, and Haemophilus influenzae type B. Infants born to
mothers with prenatal malaria, hookworm, or Schistosoma haematobium infections
were associated with a significantly reduced ratio of maternal to infant cord
blood antibody concentration for Streptococcus pneumoniae serotypes 1, 4, 5, 6B,
7F, 9V, and 18C compared to infants of uninfected mothers. Anti-diphtheria toxoid
and anti-H. influenzae type B IgG ratios were not significantly different among
infection groups. Prenatal parasitic infections decrease the transfer of maternal
IgG antibodies to infants for several serotypes of S. pneumoniae.
PMID- 28404575
TI - Dietary protein and bone health: a systematic review and meta-analysis from the
National Osteoporosis Foundation.
AB - Background: Considerable attention has recently focused on dietary protein's role
in the mature skeleton, prompted partly by an interest in nonpharmacologic
approaches to maintain skeletal health in adult life.Objective: The aim was to
conduct a systematic review and meta-analysis evaluating the effects of dietary
protein intake alone and with calcium with or without vitamin D (Ca+/-D) on bone
health measures in adults.Design: Searches across 5 databases were conducted
through October 2016 including randomized controlled trials (RCTs) and
prospective cohort studies examining 1) the effects of "high versus low" protein
intake or 2) dietary protein's synergistic effect with Ca+/-D intake on bone
health outcomes. Two investigators independently conducted abstract and full-text
screenings, data extractions, and risk of bias (ROB) assessments. Strength of
evidence was rated by group consensus. Random-effects meta-analyses for outcomes
with >=4 RCTs were performed.Results: Sixteen RCTs and 20 prospective cohort
studies were included in the systematic review. Overall ROB was medium. Moderate
evidence suggested that higher protein intake may have a protective effect on
lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake
(net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, I2: 0%; n = 5) but no effect
on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers.
Limited evidence did not support an effect of protein with Ca+/-D on LS BMD, TH
BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall
fractures.Conclusions: Current evidence shows no adverse effects of higher
protein intakes. Although there were positive trends on BMD at most bone sites,
only the LS showed moderate evidence to support benefits of higher protein
intake. Studies were heterogeneous, and confounding could not be excluded. High
quality, long-term studies are needed to clarify dietary protein's role in bone
health. This trial was registered at www.crd.york.ac.uk as CRD42015017751.
PMID- 28404576
TI - Whole dairy matrix or single nutrients in assessment of health effects: current
evidence and knowledge gaps.
AB - Foods consist of a large number of different nutrients that are contained in a
complex structure. The nature of the food structure and the nutrients therein
(i.e., the food matrix) will determine the nutrient digestion and absorption,
thereby altering the overall nutritional properties of the food. Thus, the food
matrix may exhibit a different relation with health indicators compared to single
nutrients studied in isolation. The evidence for a dairy matrix effect was
presented and discussed by an expert panel at a closed workshop, and the
following consensus was reached: 1) Current evidence does not support a positive
association between intake of dairy products and risk of cardiovascular disease
(i.e., stroke and coronary heart disease) and type 2 diabetes. In contrast,
fermented dairy products, such as cheese and yogurt, generally show inverse
associations. 2) Intervention studies have indicated that the metabolic effects
of whole dairy may be different than those of single dairy constituents when
considering the effects on body weight, cardiometabolic disease risk, and bone
health. 3) Different dairy products seem to be distinctly linked to health
effects and disease risk markers. 4) Different dairy structures and common
processing methods may enhance interactions between nutrients in the dairy
matrix, which may modify the metabolic effects of dairy consumption. 5) In
conclusion, the nutritional values of dairy products should not be considered
equivalent to their nutrient contents but, rather, be considered on the basis of
the biofunctionality of the nutrients within dairy food structures. 6) Further
research on the health effects of whole dairy foods is warranted alongside the
more traditional approach of studying the health effects of single nutrients.
Future diet assessments and recommendations should carefully consider the
evidence of the effects of whole foods alongside the evidence of the effects of
individual nutrients. Current knowledge gaps and recommendations for priorities
in future research on dairy were identified and presented.
PMID- 28404577
TI - Outpatient treatment of severe acute malnutrition: response to treatment with a
reduced schedule of therapeutic food distribution.
AB - Background: Community-based management of severe acute malnutrition (SAM) has
been shown to be safe and cost-effective, but program coverage remains low.
Treatment models that maintain high levels of clinical effectiveness but allow
for increased coverage are still needed. A reduced schedule of follow-up, in
which children receive clinical follow-up and therapeutic foods on a monthly
rather than weekly basis, may be one alternative.Objective: We aimed to describe
the safety and feasibility of a monthly distribution of ready-to-use therapeutic
food (RUTF) in the treatment of uncomplicated SAM, in terms of clinical response
to treatment and household RUTF use.Design: We conducted a nonrandomized pilot
intervention study in which 115 children eligible for outpatient treatment of SAM
were provided a monthly ration of RUTF. Anthropometric measurements were taken
weekly for 4 wk to monitor treatment response. Unannounced household spot checks
were conducted over 4 wk to assess household use of RUTF and storage
practices.Results: Adequate weight and midupper arm circumference (MUAC) gain
were found throughout the 4-wk follow-up period. Observed mean +/- SD weight gain
from admission was 9.8 +/- 6.8 g . kg-1 . d-1 in week 1 and 4.2 +/- 2.1 g . kg-1
. d-1 by week 4. Unplanned household spot checks found an average surplus of RUTF
sachets compared with the number expected based on the date of distribution and
recommended dosing throughout the 4 wk of follow-up. The frequency at which more
than the recommended dose was used (i.e., deviance of >2 sachets between
available and expected stocks) was 4% and 22% of households visited in week 1 and
week 4, respectively.Conclusion: Adequate treatment response and RUTF use in the
outpatient treatment of SAM was maintained over 4 wk of follow-up with a monthly
schedule of RUTF distribution. This study was registered at clinicaltrials.gov as
NCT02994212.
PMID- 28404578
TI - Dietary calcium intake recommendations for children: are they too high?
PMID- 28404579
TI - Glycemic index, glycemic load, and blood pressure: a systematic review and meta
analysis of randomized controlled trials.
AB - Background: High blood pressure is a strong risk factor for cardiovascular
disease.Objective: The aim of this study was to determine the associations of
dietary glycemic index (GI) and glycemic load (GL) with systolic blood pressure
(SBP) and diastolic blood pressure (DBP) in healthy individuals.Design: A
systematic review and meta-analysis of randomized controlled trials (RCTs) was
carried out. Databases were searched for eligible RCTs in 2 phases. MEDLINE,
Embase, CAB Abstracts, BIOSIS, ISI Web of Science, and the Cochrane Library were
searched from January 1990 to December 2009. An updated search was undertaken
with the use of MEDLINE and Embase from January 2010 to September 2016. Trials
were included if they reported author-defined high- and low-GI or -GL diets and
blood pressure, were of >=6 wk duration, and comprised healthy participants
without chronic conditions. Data were extracted and analyzed with the use of
Stata statistical software. Pooled estimates and 95% CIs were calculated with the
use of weighted mean differences and random-effects models.Results: Data were
extracted from 14 trials comprising 1097 participants. Thirteen trials provided
information on differences in GI between control and intervention arms. A median
reduction in GI of 10 units reduced the overall pooled estimates for SBP and DBP
by 1.1 mm Hg (95% CI: -0.3, 2.5 mm Hg; P = 0.11) and 1.3 mm Hg (95% CI: 0.2 mm
Hg, 2.3; P = 0.02), respectively. Nine trials reported information on differences
in GL between arms. A median reduction in GL of 28 units reduced the overall
pooled estimates for SBP and DBP by 2.0 mm Hg (95% CI: 0.2, 3.8 mm Hg; P = 0.03)
and 1.4 mm Hg (95% CI: 0.1, 2.6 mm Hg; P = 0.03), respectively.Conclusions: This
review of healthy individuals indicated that a lower glycemic diet may lead to
important reductions in blood pressure. However, many of the trials included in
the analysis reported important sources of bias. This trial was registered at
PROSPERO as CRD42016049026.
PMID- 28404580
TI - Effects of face/head and whole body cooling during passive heat stress on human
somatosensory processing.
AB - We herein investigated the effects of face/head and whole body cooling during
passive heat stress on human somatosensory processing recorded by somatosensory
evoked potentials (SEPs) at C4' and Fz electrodes. Fourteen healthy subjects
received a median nerve stimulation at the left wrist. SEPs were recorded at
normothermic baseline (Rest), when esophageal temperature had increased by ~1.2
degrees C (heat stress: HS) during passive heating, face/head cooling during
passive heating (face/head cooling: FHC), and after HS (whole body cooling: WBC).
The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14,
N18, P22, and N30 at Fz were evaluated. Latency indicated speed of the
subcortical and cortical somatosensory processing, while amplitude reflected the
strength of neural activity. Blood flow in the internal and common carotid
arteries (ICA and CCA, respectively) and psychological comfort were recorded in
each session. Increases in esophageal temperature due to HS significantly
decreased the amplitude of N60, psychological comfort, and ICA blood flow in the
HS session, and also shortened the latencies of SEPs (all, P < 0.05). While
esophageal temperature remained elevated, FHC recovered the peak amplitude of
N60, psychological comfort, and ICA blood flow toward preheat baseline levels as
well as WBC. However, the latencies of SEPs did not recover in the FHC and WBC
sessions. These results suggest that impaired neural activity in cortical
somatosensory processing during passive HS was recovered by FHC, whereas
conduction velocity in the ascending somatosensory input was accelerated by
increases in body temperature.
PMID- 28404582
TI - Histone deacetylase activity modulates exercise-induced skeletal muscle
plasticity in zebrafish (Danio rerio).
AB - Aerobic exercise has a positive impact on animals by enhancing skeletal muscle
function and locomotor performance. Responses of skeletal muscle to exercise
involve changes in energy metabolism, calcium handling, and the composition of
contractile protein isoforms, which together influence contractile properties.
Histone deacetylases (HDAC) can cause short-term changes in gene expression and
may thereby mediate plasticity in contractile properties of skeletal muscle in
response to exercise. The aim of this project was to determine (in zebrafish,
Danio rerio) the traits that mediate interindividual differences in sustained and
sprint performance and to determine whether inhibiting class I and II HDACs
mediates exercise-induced changes in these traits. High sustained performers had
greater aerobic metabolic capacity [citrate synthase (CS) activity], calcium
handling capacity [sarco/endoplasmic reticulum ATPase (SERCA) activity], and slow
contractile protein concentration [slow myosin heavy chain (MHC)] compared with
low performers. High sprint performers had lower CS activity and slow MHC
concentrations compared with low performers, but there were no significant
differences in lactate dehydrogenase activity or fast MHC concentrations. Four
weeks of aerobic exercise training increased sustained performance, CS activity,
SERCA activity, and slow MHC concentration. Inhibiting class I and II HDACs
increased slow MHC concentration in untrained fish but not in trained fish.
However, inhibiting HDACs reduced SERCA activity, which was paralleled by a
reduction in sustained and sprint performance. The regulation of muscle
phenotypes by HDACs could be a mechanism underlying the adaptation of sustained
locomotor performance to different environmental conditions, and may therefore be
of therapeutic and ecological significance.
PMID- 28404581
TI - Maternal and postnatal high-fat diet consumption programs energy balance and
hypothalamic melanocortin signaling in nonhuman primate offspring.
AB - Maternal high-fat-diet (HFD) consumption during pregnancy decreased fetal body
weight and impacted development of hypothalamic melanocortin neural circuitry in
nonhuman primate offspring. We investigated whether these impairments during
gestation persisted in juvenile offspring and examined the interaction between
maternal and early postnatal HFD consumption. Adult dams consumed either a
control diet (CTR; 15% calories from fat) or a high-saturated-fat diet (HFD; 37%
calories from fat) during pregnancy. Offspring were weaned onto a CTR or HFD at
~8 mo of age. Offspring from HFD-fed dams displayed early catch-up growth and
elevated body weight at 6 and 13 mo of age. Maternal and postnatal HFD exposure
reduced the amount of agouti-related peptide fibers in the paraventricular
nucleus of the hypothalamus. Postnatal HFD consumption also decreased the amount
of agouti-related peptide fibers in the arcuate nucleus of the hypothalamus.
Postnatal HFD was associated with decreased food intake and increased activity.
These results support and extend our previous findings of maternal diet effects
on fetal development and reveal, for the first time in a nonhuman primate model,
that maternal HFD-induced disturbances in offspring body weight regulation
extended past gestation into the juvenile period. Maternal HFD consumption
increases the risk for offspring developing obesity, with the developmental
timing of HFD exposure differentially impacting the melanocortin system and
energy balance regulation. The present findings provide translational insight
into human clinical populations, suggesting that profound health consequences may
await individuals later in life following intrauterine and postnatal HFD
exposure.
PMID- 28404585
TI - Nita Gandhi Forouhi: Challenging poor choices.
PMID- 28404584
TI - Authors' reply to Fralick and Kesselheim.
PMID- 28404583
TI - Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the
paraventricular nucleus of the hypothalamus: differential role of nitric oxide.
AB - Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and
compensatory increases in breathing, sympathetic outflow, and neuroendocrine
secretions, including increased secretion of AVP, corticotropin-releasing hormone
(CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a
brain stem pathway, including the nucleus tractus solitarius (nTS) and the
rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular
nucleus of the hypothalamus (PVN) contribute to chemoreflex responses.
Experiments evaluated activation of specific cell phenotypes within the PVN
following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats.
Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS)
neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR)
cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR
(~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that
sympathoexcitation during moderate AH is mediated mainly by a pathway that does
not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell
phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH
activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR
neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were
closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external
zone, where vascular NO participates in tanycyte retraction to facilitate
neuropeptide secretion into the pituitary portal circulation. Results are
consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and
an excitatory role of NO on CRH secretion in the PVN and median eminence.
PMID- 28404586
TI - Refractory hypokalaemia in an elderly patient.
PMID- 28404587
TI - CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma.
AB - CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round
cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES).
However, recent clinicopathologic and molecular genetic analyses indicate that
CDS is an independent disease entity from ES. Few ancillary markers have been
used in the differential diagnosis of CDS, and additional CDS-specific biomarkers
are needed for more definitive classification. Here, we report the generation of
an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC)
with human CIC-DUX4 cDNA. Recipient mice transplanted with eMC-expressing CIC
DUX4 rapidly developed an aggressive, undifferentiated sarcoma composed of small
round to short spindle cells. Gene-expression profiles of CDS and eMC revealed
upregulation of CIC-DUX4 downstream genes such as PEA3 family genes, Ccnd2, Crh,
and Zic1 IHC analyses for both mouse and human tumors showed that CCND2 and
MUC5AC are reliable biomarkers to distinguish CDS from ES. Gene silencing of CIC
DUX4 as well as Ccnd2, Ret, and Bcl2 effectively inhibited CDS tumor growth in
vitro The CDK4/6 inhibitor palbociclib and the soft tissue sarcoma drug
trabectedin also blocked the growth of mouse CDS. In summary, our mouse model
provides important biological information about CDS and provides a useful
platform to explore biomarkers and therapeutic agents for CDS. Cancer Res;
77(11); 2927-37. (c)2017 AACR.
PMID- 28404588
TI - Adaptive functional change of the contralateral kidney after partial nephrectomy.
AB - Partial nephrectomy aims to maintain renal function by nephron sparing; however,
functional changes in the contralateral kidney remain unknown. We evaluate the
functional change in the contralateral kidney using a diethylene triamine penta
acetic acid (DTPA) renal scan and determine factors predicting contralateral
kidney function after partial nephrectomy. A total of 699 patients underwent
partial nephrectomy, with a DTPA scan before and after surgery to assess the
separate function of each kidney. Patients were divided into three groups
according to initial contralateral glomerular filtration rate (GFR; group 1: <30
ml.min-1.1.73 m-2, group 2: 30-45 ml.min-1.1.73 m-2, and group 3: >=45 ml.min
1.1.73 m-2). Multiple-regression analysis was used to identify the factors
associated with increased GFR of the contralateral kidney over a 4-yr
postoperative period. Patients in group 1 had a higher mean age and hypertension
history, worse American Society of Anesthesiologists score, and larger tumor size
than in the other two groups. The ipsilateral GFR changes at 4 yr after partial
nephrectomy were -18.9, -3.6, and 3.9% in groups 1, 2, and 3, respectively,
whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [beta:
0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative
contralateral GFR (beta: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were
significant predictive factors for increased GFR of the contralateral kidney
after 4 yr. The contralateral kidney compensated for the functional loss of the
ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent
in younger patients with decreased contralateral renal function.
PMID- 28404589
TI - Autophagy is activated to protect against podocyte injury in adriamycin-induced
nephropathy.
AB - Podocytes are highly differentiated epithelial cells wrapping glomerular
capillaries to form the filtration barrier in kidneys. As such, podocyte injury
or dysfunction is a critical pathogenic event in glomerular disease. Autophagy
plays an important role in the maintenance of the homeostasis and function of
podocytes. However, it is less clear whether and how autophagy contributes to
podocyte injury in glomerular disease. Here, we have examined the role of
autophagy in adriamycin-induced nephropathy, a classic model of glomerular
disease. We show that autophagy was induced by adriamycin in cultured podocytes
in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy
with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas
inhibition of autophagy with chloroquine enhanced podocyte apoptosis during
adriamycin treatment. To determine the role of autophagy in vivo, we established
an inducible podocyte-specific autophagy-related gene 7 knockout mouse model
(Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed
higher levels of podocyte injury, glomerulopathy, and proteinuria during
adriamycin treatment. Together, these observations support an important role of
autophagy in protecting podocytes under the pathological conditions of glomerular
disease, suggesting the therapeutic potential of autophagy induction.
PMID- 28404590
TI - Inflammatory cytokines regulate renal sodium transporters: how, where, and why?
AB - Hypertension is growing in epidemic proportions worldwide and is now the leading
preventable cause of premature death. For over a century, we have known that the
kidney plays a critical role in blood pressure regulation. Specifically,
abnormalities in renal sodium transport appear to be a final common pathway that
gives rise to elevated blood pressure regardless of the nature of the initial
hypertensive stimulus. However, it is only in the past decade that we have come
to realize that inflammatory cytokines secreted by innate and adaptive immune
cells, as well as renal epithelial cells, can modulate the expression and
activity of sodium transporters all along the nephron, leading to alterations in
pressure natriuresis, sodium and water balance, and ultimately hypertension. This
mini-review highlights specific cytokines and the transporters that they regulate
and discusses why inflammatory cytokines may have evolved to serve this function.
PMID- 28404592
TI - Accounting for oxygen in the renal cortex: a computational study of factors that
predispose the cortex to hypoxia.
AB - We develop a pseudo-three-dimensional model of oxygen transport for the renal
cortex of the rat, incorporating both the axial and radial geometry of the
preglomerular circulation and quantitative information regarding the surface
areas and transport from the vasculature and renal corpuscles. The computational
model was validated by simulating four sets of published experimental studies of
renal oxygenation in rats. Under the control conditions, the predicted cortical
tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension
(uPo2) were within +/-1 SE of the mean value observed experimentally. The
predicted [Formula: see text] or uPo2 in response to ischemia-reperfusion injury,
acute hemodilution, blockade of nitric oxide synthase, or uncoupling
mitochondrial respiration, were within +/-2 SE observed experimentally. We
performed a sensitivity analysis of the key model parameters to assess their
individual or combined impact on the predicted [Formula: see text] and uPo2 The
model parameters analyzed were as follows: 1) the major determinants of renal
oxygen delivery ([Formula: see text]) (arterial blood Po2, hemoglobin
concentration, and renal blood flow); 2) the major determinants of renal oxygen
consumption (Vo2) [glomerular filtration rate (GFR) and the efficiency of oxygen
utilization for sodium reabsorption (beta)]; and 3) peritubular capillary surface
area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the
sensitivity of [Formula: see text] and uPo2 to the major the determinants of
[Formula: see text] and Vo2 The increasing likelihood of hypoxia with decreasing
PCSA provides a potential explanation for the increased risk of acute kidney
injury in some experimental animals and for patients with chronic kidney disease.
PMID- 28404591
TI - Intravital imaging of the kidney in a rat model of salt-sensitive hypertension.
AB - Hypertension is one of the most prevalent diseases worldwide and a major risk
factor for renal failure and cardiovascular disease. The role of albuminuria, a
common feature of hypertension and robust predictor of cardiorenal disorders,
remains incompletely understood. The goal of this study was to investigate the
mechanisms leading to albuminuria in the kidney of a rat model of hypertension,
the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the
glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two
photon-based imaging to investigate the complex renal physiological changes that
occur during salt-induced hypertension. Following a high-salt diet, SS rats
exhibited elevated blood pressure, increased glomerular sieving of albumin
(GSCalb = 0.0686), relative permeability to albumin (+Delta16%), and impaired
volume hemodynamics (-Delta14%). Serum albumin but not serum globulins or
creatinine concentration was decreased (-0.54 g/dl), which was concomitant with
increased filtration of albumin (3.7 vs. 0.8 g/day normal diet). Pathologically,
hypertensive animals had significant tubular damage, as indicated by increased
prevalence of granular casts, expansion and necrosis of PT epithelial cells
(+Delta2.20 score/image), progressive augmentation of red blood cell velocity
(+Delta269 um/s) and micro vessel diameter (+Delta4.3 um), and increased vascular
injury (+Delta0.61 leakage/image). Therefore, development of salt-induced
hypertension can be triggered by fast and progressive pathogenic remodeling of PT
epithelia, which can be associated with changes in albumin handling.
Collectively, these results indicate that both the glomerulus and the PT
contribute to albuminuria, and dual treatment of glomerular filtration and
albumin reabsorption may represent an effective treatment of salt-sensitive
hypertension.
PMID- 28404593
TI - Physiopathological implications of P2X1 and P2X7 receptors in regulation of
glomerular hemodynamics in angiotensin II-induced hypertension.
AB - Deleterious effects of purinergic P2X1 and P2X7 receptors (P2XRs) in ANG II
dependent hypertension include increased renal vascular resistance, and impaired
autoregulation and pressure natriuresis. However, their specific effects on the
determinants of glomerular hemodynamics remain incompletely delineated. To
investigate the P2XR contributions to altered glomerular hemodynamics in
hypertension, the effects of acute blockade of P2X1R, P2X7R, and P2X4R with
NF449, A438079, and PSB12054, respectively, were evaluated in ANG II-infused rats
(435 ng.kg-1.min-1). P2X1R or P2X7R blockade reduced afferent (6.85 +/- 1.05 vs.
2.37 +/- 0.20 dyn.s-1.cm-5) and efferent (2.85 +/- 0.38 vs. 0.99 +/- 0.07 dyn.s
1.cm-5) arteriolar resistances, leading to increases in glomerular plasma flow
(75.82 +/- 5.58 vs. 206.7 +/- 16.38 nl/min), ultrafiltration coefficient (0.0198
+/- 0.0024 vs. 0.0512 +/- 0.0046 nl.min-1.mmHg-1), and single-nephron glomerular
filtration rate (22.73 +/- 2.02 vs. 51.56 +/- 3.87 nl/min) to near normal values.
Blockade of P2X4R did not elicit effects in hypertensive rats. In normotensive
sham-operated rats, only the P2X1R antagonist caused an increase plasma flow and
single-nephron glomerular filtration rate, whereas the P2X4R antagonist induced
glomerular vasoconstriction that was consistent with evidence that P2X4R
stimulation increases release of nitric oxide from endothelial cells. Mean
arterial pressure remained unchanged in both hypertensive and normotensive
groups. Western blot analysis showed overexpression of P2X1R, P2X7R, and P2X4R
proteins in hypertensive rats. Whereas it has been generally assumed that the
altered glomerular vascular resistances in ANG II hypertension are due to AT1
receptor-mediated vasoconstriction, these data indicate a predominant P2X1R and
P2X7R control of glomerular hemodynamics in ANG II hypertension.
PMID- 28404594
TI - Health-related quality of life of patients with hypothalamic-pituitary-adrenal
axis dysregulations: a cohort study.
AB - OBJECTIVE: Health-related quality of life (HrQoL) is increasingly considered to
be an important outcome of care for hypothalamic-pituitary-adrenal (HPA) axis
dysregulation. The objective of this study was to assess the influence of type of
HPA axis dysregulation and cortisol status on HrQOL and its evolution with time
and treatment. DESIGN: Prospective cohort study. METHODS: Between September 2007
and April 2014, HrQoL questionnaires were administered during routine management
to all patients with HPA axis dysregulation hospitalized in a single department,
and this was repeated after 6- 12-, 24- and 36-month during standard follow-up.
The Medical Outcomes Study 36-item short-form health survey (SF-36) and the
General Health Questionnaire 12 (GHQ-12) were used simultaneously, with a common
time schedule to measure the impact of HPA axis dysregulation on HrQoL.
Multivariate mixed linear regression models were constructed to adjust for
potential confounders. RESULTS: 343 patients (206 with Cushing's syndrome of
pituitary origin, 91 with Cushing's syndrome of adrenal origin and 46 with
Addison's disease) responded to the questionnaires. Overall, HrQoL scores were
well below population values. Cushing syndrome of pituitary origin was associated
with worse HrQoL, especially in physical dimensions. More than half of the
patients, of all diagnoses and cortisol status, had psychological distress
requiring attention according to the GHQ-12. Hypercortisolism had the greatest
negative influence on HrQoL. CONCLUSIONS: HRQoL appears significantly altered by
all forms of HPA axis dysregulation, and most substantially and broadly by
Cushing's syndrome, notably during periods of hypercortisolism. These effects on
HRQoL deserve further consideration both in clinical practice and research.
PMID- 28404596
TI - Tumor Necrosis Factor-alpha Promotes Phosphoinositide 3-Kinase Enhancer A and AMP
Activated Protein Kinase Interaction to Suppress Lipid Oxidation in Skeletal
Muscle.
AB - Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine that plays a
central role in obesity-induced insulin resistance. It also controls cellular
lipid metabolism, but the underlining mechanism is poorly understood. We report
in this study that phosphoinositide 3-kinase enhancer A (PIKE-A) is a novel
effector of TNF-alpha to facilitate its metabolic modulation in the skeletal
muscle. Depletion of PIKE-A in C2C12 myotubes diminished the inhibitory
activities of TNF-alpha on mitochondrial respiration and lipid oxidation, whereas
PIKE-A overexpression exacerbated these cellular responses. We also found that
TNF-alpha promoted the interaction between PIKE-A and AMP-activated protein
kinase (AMPK) to suppress its kinase activity in vitro and in vivo. As a result,
animals with PIKE ablation in the skeletal muscle per se display an upregulation
of AMPK phosphorylation and a higher preference to use lipid as the energy
production substrate under high-fat diet feeding, which mitigates the development
of diet-induced hyperlipidemia, ectopic lipid accumulation, and muscle insulin
resistance. Hence, our data reveal PIKE-A as a new signaling factor that is
important for TNF-alpha-initiated metabolic changes in skeletal muscle.
PMID- 28404597
TI - Altered miR-29 Expression in Type 2 Diabetes Influences Glucose and Lipid
Metabolism in Skeletal Muscle.
AB - MicroRNAs have emerged as important regulators of glucose and lipid metabolism in
several tissues; however, their role in skeletal muscle remains poorly
characterized. We determined the effects of the miR-29 family on glucose
metabolism, lipid metabolism, and insulin responsiveness in skeletal muscle. We
provide evidence that miR-29a and miR-29c are increased in skeletal muscle from
patients with type 2 diabetes and are decreased following endurance training in
healthy young men and in rats. In primary human skeletal muscle cells, inhibition
and overexpression strategies demonstrate that miR-29a and miR-29c regulate
glucose uptake and insulin-stimulated glucose metabolism. We identified that miR
29 overexpression attenuates insulin signaling and expression of insulin receptor
substrate 1 and phosphoinositide 3-kinase. Moreover, miR-29 overexpression
reduces hexokinase 2 expression and activity. Conversely, overexpression of miR
29 by electroporation of mouse tibialis anterior muscle decreased glucose uptake
and glycogen content in vivo, concomitant with decreased abundance of GLUT4. We
also provide evidence that fatty acid oxidation is negatively regulated by miR-29
overexpression, potentially through the regulation of peroxisome proliferator
activated receptor gamma coactivator-1alpha expression. Collectively, we reveal
that miR-29 acts as an important regulator of insulin-stimulated glucose
metabolism and lipid oxidation, with relevance to human physiology and type 2
diabetes.
PMID- 28404598
TI - Cognitive-behavioural therapy for insomnia is effective, safe and highly
deployable.
PMID- 28404595
TI - NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia
and astrocytes.
AB - Inflammation in the brain accompanies several high-impact neurological diseases
including multiple sclerosis (MS), stroke, and Alzheimer's disease.
Neuroinflammation is sterile, as damage-associated molecular patterns rather than
microbial pathogens elicit the response. The inflammasome, which leads to caspase
1 activation, is implicated in neuroinflammation. In this study, we reveal that
lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and
demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and
astrocytes, which are central players in neuroinflammation. LPC-activated
inflammasome also requires ASC (apoptotic speck containing protein with a CARD),
caspase-1, cathepsin-mediated degradation, calcium mobilization, and potassium
efflux but not caspase-11. To study the physiological relevance, Nlrc4-/- and
Nlrp3-/- mice are studied in the cuprizone model of neuroinflammation and
demyelination. Mice lacking both genes show the most pronounced reduction in
astrogliosis and microglial accumulation accompanied by decreased expression of
the LPC receptor G2A, whereas MS patient samples show increased G2A. These
results reveal that NLRC4 and NLRP3, which normally form distinct inflammasomes,
activate an LPC-induced inflammasome and are important in astrogliosis and
microgliosis.
PMID- 28404599
TI - Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression
in Cancer.
AB - Epigenetic alterations contribute to tumor development, progression, and
therapeutic response. Many epigenetic enzymes use metabolic intermediates as
cofactors to modify chromatin structure. Emerging evidence suggests that
fluctuation in metabolite levels may regulate activities of these chromatin
modifying enzymes. Here, we summarize recent progress in understanding the cross
talk between metabolism and epigenetic control of gene expression in cancer. We
focus on how metabolic changes, due to diet, genetic mutations, or tumor
microenvironment, regulate histone methylation status and, consequently, affect
gene expression profiles to promote tumorigenesis. Importantly, we also suggest
some potential therapeutic approaches to target the oncogenic role of metabolic
alterations and epigenetic modifications in cancer. Clin Cancer Res; 23(15); 4004
9. (c)2017 AACR.
PMID- 28404601
TI - Federal Funding Insulated State Budgets From Increased Spending Related To
Medicaid Expansion.
AB - As states weigh whether to expand Medicaid under the Affordable Care Act (ACA)
and Medicaid reform remains a priority for some federal lawmakers, fiscal
considerations loom large. As part of the ACA's expansion of eligibility for
Medicaid, the federal government paid for 100 percent of the costs for newly
eligible Medicaid enrollees for the period 2014-16. In 2017 states will pay some
of the costs for new enrollees, with each participating state's share rising to
10 percent by 2020. States continue to pay their traditional Medicaid share
(roughly 25-50 percent, depending on the state) for previously eligible
enrollees. We used data for fiscal years 2010-15 from the National Association of
State Budget Officers and a difference-in-differences framework to assess the
effects of the expansion's first two fiscal years. We found that the expansion
led to an 11.7 percent increase in overall spending on Medicaid, which was
accompanied by a 12.2 percent increase in spending from federal funds. There were
no significant increases in spending from state funds as a result of the
expansion, nor any significant reductions in spending on education or other
programs. States' advance budget projections were also reasonably accurate in the
aggregate, with no significant differences between the projected levels of
federal, state, and Medicaid spending and the actual expenses as measured at the
end of the fiscal year.
PMID- 28404600
TI - Qualitative Interviews Exploring Palliative Care Perspectives of Latinos on
Dialysis.
AB - BACKGROUND AND OBJECTIVES: Compared with non-Latino whites with advanced illness,
Latinos are less likely to have an advance directive or to die with hospice
services. To improve palliative care disparities, international ESRD guidelines
call for increased research on culturally responsive communication of advance
care planning (ACP). The objective of our study was to explore the preferences of
Latino patients receiving dialysis regarding symptom management and ACP. DESIGN,
SETTING, PARTICIPANTS, & MEASUREMENTS: Qualitative study design using
semistructured face-to-face interviews of 20 Latinos on hemodialysis between
February and July of 2015. Data were analyzed using thematic analysis. RESULTS:
Four themes were identified: Avoiding harms of medication (fear of addiction and
damage to bodies, effective distractions, reliance on traditional remedies,
fatalism: the sense that one's illness is deserved punishment); barriers and
facilitators to ACP: faith, family, and home (family group decision-making,
family reluctance to have ACP conversations, flexible decision-making
conversations at home with family, ACP conversations incorporating trust and
linguistic congruency, family-first and faith-driven decisions); enhancing
wellbeing day-to-day (supportive relationships, improved understanding of illness
leads to adherence, recognizing new self-value, maintaining a positive outlook);
and distressing aspects of living with their illness (dietary restriction is
culturally isolating and challenging for families, logistic challenges and
socioeconomic disadvantage compounded by health literacy and language barriers,
required rapid adjustments to chronic illness, demanding dialysis schedule).
CONCLUSIONS: Latinos described unique cultural preferences such as avoidance of
medications for symptom alleviation and a preference to have family group
decision-making and ACP conversations at home. Understanding and integrating
cultural values and preferences into palliative care offers the potential to
improve disparities and achieve quality patient-centered care for Latinos with
advanced illness.
PMID- 28404602
TI - Stroke rates vary substantially across cohorts of patients with atrial
fibrillation.
PMID- 28404603
TI - Clinical failure is more common in young children with acute otitis media who
receive a short course of antibiotics compared with standard duration.
PMID- 28404604
TI - Unusual semi-extractability as a hallmark of nuclear body-associated
architectural noncoding RNAs.
AB - NEAT1_2 long noncoding RNA (lncRNA) is the molecular scaffold of paraspeckle
nuclear bodies. Here, we report an improved RNA extraction method: extensive
needle shearing or heating of cell lysate in RNA extraction reagent improved
NEAT1_2 extraction by 20-fold (a property we term "semi-extractability"), whereas
using a conventional method NEAT1_2 was trapped in the protein phase. The
improved extraction method enabled us to estimate that approximately 50 NEAT1_2
molecules are present in a single paraspeckle. Another architectural lncRNA,
IGS16, also exhibited similar semi-extractability. A comparison of RNA-seq data
from needle-sheared and control samples revealed the existence of multiple semi
extractable RNAs, many of which were localized in subnuclear granule-like
structures. The semi-extractability of NEAT1_2 correlated with its association
with paraspeckle proteins and required the prion-like domain of the RNA-binding
protein FUS This observation suggests that tenacious RNA-protein and protein
protein interactions, which drive nuclear body formation, are responsible for
semi-extractability. Our findings provide a foundation for the discovery of the
architectural RNAs that constitute nuclear bodies.
PMID- 28404605
TI - Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as
Inducers of Tube Morphogenesis Defects in Drosophila melanogaster.
AB - Elevated levels of human chitinase-like proteins (CLPs) are associated with
numerous chronic inflammatory diseases and several cancers, often correlating
with poor prognosis. Nevertheless, there is scant knowledge of their function.
The CLPs normally mediate immune responses and wound healing and, when
upregulated, they can promote disease progression by remodeling tissue,
activating signaling cascades, stimulating proliferation and migration, and by
regulating adhesion. We identified Imaginal disc growth factors (Idgfs),
orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis
designed to discover factors that regulate tube morphogenesis in a Drosophila
melanogaster model of tube formation. We implemented a novel approach that uses
magnetic beads to isolate a small population of specialized ovarian cells, cells
that nonautonomously regulate morphogenesis of epithelial tubes that form and
secrete eggshell structures called dorsal appendages (DAs). Differential mass
spectrometry analysis of these cells detected elevated levels of four of the six
Idgf family members (Idgf1, Idgf2, Idgf4, and Idgf6) in flies mutant for
bullwinkle (bwk), which encodes a transcription factor and is a known regulator
of DA-tube morphogenesis. We show that, during oogenesis, dysregulation of Idgfs
(either gain or loss of function) disrupts the formation of the DA tubes.
Previous studies demonstrate roles for Drosophila Idgfs in innate immunity, wound
healing, and cell proliferation and motility in cell culture. Here, we identify a
novel role for Idgfs in both normal and aberrant tubulogenesis processes.
PMID- 28404608
TI - Discerning From the Good, the Bad, and the Ugly.
PMID- 28404607
TI - Interpreting Incidentally Identified Variants in Genes Associated With
Catecholaminergic Polymorphic Ventricular Tachycardia in a Large Cohort of
Clinical Whole-Exome Genetic Test Referrals.
AB - BACKGROUND: The rapid expansion of genetic testing has led to increased
utilization of clinical whole-exome sequencing (WES). Clinicians and genetic
researchers are being faced with assessing risk of disease vulnerability from
incidentally identified genetic variants which is typified by variants found in
genes associated with sudden death-predisposing catecholaminergic polymorphic
ventricular tachycardia (CPVT). We sought to determine whether incidentally
identified variants in genes associated with CPVT from WES clinical testing
represent disease-associated biomarkers. METHODS AND RESULTS: CPVT-associated
genes RYR2 and CASQ2 variants were identified in one of the world's largest
collections of clinical WES referral tests (N=6517, Baylor Miraca Genetics
Laboratories) and compared with a control cohort of ostensibly healthy
individuals (N=60 706) and a case cohort of CPVT cases (N=155). Within the WES
cohort, the rate of rare variants in CPVT-associated genes was 8.8% compared with
6.0% among controls and 60.0% among cases. There was a predominance of variants
of undetermined significance (97.7%). After protein topology mapping, WES
variants colocalized more frequently to residues with variants found in controls
compared with cases. Retrospective clinical evaluation of individuals referred to
our institution with WES-positive variants demonstrated no evidence of clinical
CPVT in individuals with a low pretest clinical suspicion for CPVT. CONCLUSIONS:
The prevalence of incidentally identified CPVT-associated variants is ~9% among
WES tests. Variants of undetermined significances in CPVT-associated genes in WES
genetic testing, in the absence of clinical suspicion for CPVT, are unlikely to
represent markers of CPVT pathogenicity.
PMID- 28404606
TI - Local translation in neuronal compartments: how local is local?
AB - Efficient neuronal function depends on the continued modulation of the local
neuronal proteome. Local protein synthesis plays a central role in tuning the
neuronal proteome at specific neuronal regions. Various aspects of translation
such as the localization of translational machinery, spatial spread of the newly
translated proteins, and their site of action are carried out in specialized
neuronal subcompartments to result in a localized functional outcome. In this
review, we focus on the various aspects of these local translation compartments
such as size, biochemical and organelle composition, structural boundaries, and
temporal dynamics. We also discuss the apparent absence of definitive components
of translation in these local compartments and the emerging state-of-the-art
tools that could help dissecting these conundrums in greater detail in the
future.
PMID- 28404609
TI - Moxibustion versus diclofenac sodium gel for the treatment of knee
osteoarthritis: a study protocol for a double-blinded, double-placebo, randomised
controlled trial.
AB - INTRODUCTION: Knee osteoarthritis is a common form of arthritis in elderly
patients that is characterised by pain and functional limitation. Moxibustion has
been employed to relieve chronic pain as an alternative therapy for knee
osteoarthritis. However, the evidence of its efficacy is equivocal due to the low
methodological quality in most clinical studies. Therefore, we are performing a
double-blinded, double-placebo, randomised controlled trial to evaluate the
efficacy of moxibustion in participants with knee osteoarthritis. METHODS AND
ANALYSIS: This is a multicentre, double-blinded, double-placebo, randomised
controlled clinical trial. 144 eligible participants with knee osteoarthritis
will be randomly assigned to two different groups in a 1:1 ratio. Participants in
the moxibustion group will undergo active moxibustion plus placebo gel, whereas
participants in the control group will receive diclofenac sodium gel plus placebo
moxibustion. Each participant will receive 12 sessions of active/placebo
moxibustion at three acupoints (ST35, ST36 and EX-LE4) as well as 2 months of
follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee will be
applied three times per day for 4 weeks. The primary outcome measure will be the
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
change at the end of the intervention period from baseline. The secondary outcome
measures include changes of other subscales (pain, stiffness and function) of
WOMAC, visual analogue scale and patient globalassessment. The safety of
moxibustion and diclofenac sodium gel will be assessed at every visit. ETHICS AND
DISSEMINATION: This trial has been approved by the Sichuan Regional Ethics Review
Committee (permission number: 2015KL-014). The results of this study are expected
to provide clinical evidence on the efficacy of moxibustion for pain relief and
physical function improvement in patients with knee osteoarthritis. The findings
will be submitted for publication in peer-reviewed medical journals and presented
at relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT02769572.
PMID- 28404610
TI - Hand exercises for patients with rheumatoid arthritis: an extended follow-up of
the SARAH randomised controlled trial.
AB - OBJECTIVES: The Stretching And strengthening for Rheumatoid Arthritis of the Hand
(SARAH) randomised controlled trial evaluated the effectiveness of a hand
exercise programme and demonstrated it was clinically effective and cost
effective at 12 months. The aim of this extended follow-up was to evaluate the
effects of the SARAH programme beyond 12 months. METHODS: Using postal
questionnaires, we collected the Michigan Hand Questionnaire hand function
(primary outcome), activities of daily living and work subscales, pain
troublesomeness, self-efficacy and health-related quality of life. All
participants were asked how often they performed hand exercises for their
rheumatoid arthritis. Mean difference in hand function scores were analysed by a
linear model, adjusted for baseline score. RESULTS: Two-thirds (n=328/490, 67%)
of the original cohort provided data for the extended follow-up. The mean follow
up time was 26 months (range 19-40 months).There was no difference in change in
hand function scores between the two groups at extended follow-up (mean
difference (95% CI) 1.52 (-1.71 to 4.76)). However, exercise group participants
were still significantly improved compared with baseline (p=0.0014) unlike the
best practice usual care group (p=0.1122). Self-reported performance of hand
exercises had reduced substantially. CONCLUSIONS: Participants undertaking the
SARAH exercise programme had improved hand function compared with baseline >2
years after randomisation. This was not the case for the control group. However,
scores were no longer statistically different between the groups indicating the
effect of the programme had diminished over time. This reduction in hand function
compared with earlier follow-up points coincided with a reduction in self
reported performance of hand exercises. Further intervention to promote long-term
adherence may be warranted. TRIAL REGISTRATION NUMBER: ISRCTN89936343; Results.
PMID- 28404611
TI - Linkage into care among newly diagnosed HIV-positive individuals tested through
outreach and facility-based HIV testing models in Mbeya, Tanzania: a prospective
mixed-method cohort study.
AB - OBJECTIVE: Linkage to care is the bridge between HIV testing and HIV treatment,
care and support. In Tanzania, mobile testing aims to address historically low
testing rates. Linkage to care was reported at 14% in 2009 and 28% in 2014. The
study compares linkage to care of HIV-positive individuals tested at
mobile/outreach versus public health facility-based services within the first 6
months of HIV diagnosis. SETTING: Rural communities in four districts of Mbeya
Region, Tanzania. PARTICIPANTS: A total of 1012 newly diagnosed HIV-positive
adults from 16 testing facilities were enrolled into a two-armed cohort and
followed for 6 months between August 2014 and July 2015. 840 (83%) participants
completed the study. MAIN OUTCOME MEASURES: We compared the ratios and time
variance in linkage to care using the Kaplan-Meier estimator and Log rank tests.
Cox proportional hazards regression models to evaluate factors associated with
time variance in linkage. RESULTS: At the end of 6 months, 78% of all respondents
had linked into care, with differences across testing models. 84% (CI 81% to 87%,
n=512) of individuals tested at facility-based site were linked to care compared
to 69% (CI 65% to 74%, n=281) of individuals tested at mobile/outreach. The
median time to linkage was 1 day (IQR: 1-7.5) for facility-based site and 6 days
(IQR: 3-11) for mobile/outreach sites. Participants tested at facility-based site
were 78% more likely to link than those tested at mobile/outreach when other
variables were controlled (AHR=1.78; 95% CI 1.52 to 2.07). HIV status disclosure
to family/relatives was significantly associated with linkage to care (AHR=2.64;
95% CI 2.05 to 3.39). CONCLUSIONS: Linkage to care after testing HIV positive in
rural Tanzania has increased markedly since 2014, across testing models.
Individuals tested at facility-based sites linked in significantly higher
proportion and modestly sooner than mobile/outreach tested individuals.
Mobile/outreach testing models bring HIV testing services closer to people.
Strategies to improve linkage from mobile/outreach models are needed.
PMID- 28404612
TI - Systematic approach to evaluating and confirming the utility of a suite of
national health system performance (HSP) indicators in Canada: a modified Delphi
study.
AB - OBJECTIVES: Evaluating an existing suite of health system performance (HSP)
indicators for continued reporting using a systematic criteria-based assessment
and national consensus conference. DESIGN: Modified Delphi approach with
technical and leadership groups, an online survey of stakeholders and convening a
national consensus conference. SETTING: A national health information steward,
the Canadian Institute for Health Information (CIHI). PARTICIPANTS: A total of 73
participants, comprised 61 conference attendants/stakeholders from across Canada
and 12 national health information steward staff. PRIMARY AND SECONDARY OUTCOME
MEASURES: Indicator dispositions of retention, additional stakeholder
consultation, further redevelopment or retirement. RESULTS: 4 dimensions
(usability, importance, scientific soundness and feasibility) typically used to
select measures for reporting were expanded to 18 criteria grouped under the 4
dimensions through a process of research and testing. Definitions for each
criterion were developed and piloted. Once the definitions were established, 56
of CIHI's publicly reported HSP indicators were evaluated against the criteria
using modified Delphi approaches. Of the 56 HSP indicators evaluated, 9 measures
were ratified for retirement, 7 were identified for additional consultation and 3
for further research and development. A pre-Consensus Conference survey
soliciting feedback from stakeholders on indicator recommendations received 48
responses (response rate of 79%). CONCLUSIONS: A systematic evaluation of HSP
indicators informed the development of objective recommendations for continued
reporting. The evaluation was a fruitful exercise to identify technical
considerations for calculating indicators, furthering our understanding of how
measures are used by stakeholders, as well as harmonising actions that could be
taken to ensure relevancy, reduce indicator chaos and build consensus with
stakeholders.
PMID- 28404613
TI - Risk factors of non-specific neck pain and low back pain in computer-using office
workers in China: a cross-sectional study.
AB - OBJECTIVES: Several studies have found that inappropriate workstations are
associated with musculoskeletal disorders. The present cross-sectional study
aimed to identify the risk factors of non-specific neck pain (NP) and low back
pain (LBP) among computer-using workers. DESIGN: Observational study with a cross
sectional sample. SETTING: This study surveyed 15 companies in Zhejiang province,
China. PARTICIPANTS: After excluding participants with missing variables, 417
office workers, including 163 men and 254 women, were analyzed. OUTCOME MEASURES:
Demographic information was collected by self-report. The standard Northwick Park
Neck Pain Questionnaire and Oswestry Low Back Pain Disability Index, along with
other relevant questions, were used to assess the presence of potential
occupational risk factors and the perceived levels of pain. Multinomial logistic
regression analysis, adjusted for age, sex, body mass index, education, marital
status and neck/low back injury, was performed to identify significant risk
factors. RESULTS: Compared with low-level NP, the computer location (monitor not
in front of the operator, but on the right or left side) was associated with ORs
of 2.6 and 2.9 for medium- and high-level NP, respectively. For LBP, the computer
location (monitor not in front) was associated with an OR of 3.2 for high-level
pain, as compared with low-level pain, in females. Significant associations were
also observed between the office temperature and LBP (OR 5.4 for high vs low),
and between office work duration >=5 years and NP in female office workers (OR
2.7 for medium vs low). CONCLUSIONS: Not having the computer monitor located in
front of the operator was found to be an important risk factor for NP and LBP in
computer-using female workers. This information may not only enable the
development of potential preventive strategies but may also provide new insights
for designing appropriate workstations.
PMID- 28404614
TI - Cohort profile: a data linkage cohort to examine health service profiles of
people with intellectual disability in New South Wales, Australia.
AB - PURPOSE: People with intellectual disability are a minority group who experience
poorer physical and mental health than the general population and have difficulty
accessing healthcare services. There is lack of knowledge about healthcare
service needs and gaps experienced by people with intellectual disability. This
study aims to interrogate a large linked administrative data set containing
hospital admissions, presentations to emergency departments (ED) and mortality
data to provide evidence to inform the development of improved health and mental
health services for this population. PARTICIPANTS: A retrospective cohort of
people with intellectual disability (n=51 452) from New South Wales (NSW),
Australia, to explore health and mental health profiles, mortality, pattern of
health service use and associated costs between 2005 and 2013. The cohort is
drawn from: the Disability Services Minimum Data Set; Admitted Patients Data
Collection; Emergency Department Data Collection, Australian Bureau of Statistics
Death Registry and Registry of Births, Deaths and Marriages. Mental health
service usage among those with intellectual disability will be compared to a
cohort of people who used mental health services (n=1 073 139) and service usage
other than for mental health will be compared with published data from the
general population. FINDINGS TO DATE: The median age of the cohort was 24 at the
time of the last hospital admission and 21 at the last ED presentation. The
cohort has a higher proportion of men than women and accounts for 0.6% of the NSW
population in 2011. Over 70% had up to 5 ED presentations and hospitalisations
between 2005 and 2012. A high proportion of people with intellectual disability
live in the most disadvantaged neighbourhoods. FUTURE PLANS: Results will be used
to inform the development of more responsive healthcare, including improved
interactions between health, social and disability supports. More generally, the
results will assist the development of more inclusive policy frameworks for
people with intellectual disability.
PMID- 28404616
TI - Progress in Pharmacological Sciences in China.
AB - Pharmacology is the science that investigates the interactions between organisms
and drugs and their mechanisms. Pharmacology plays a translational role in modern
medicine, bridging basic research and the clinic. With its economy booming, China
has invested an enormous amount of financial and human resources in
pharmacological research in the recent decade. As a result, major breakthroughs
have been achieved in both basic and clinical research, with the discovery of
many potential drug targets and biomarkers that has made a sizable contribution
to the overall advancement of pharmacological sciences. In this article, we
review recent research efforts and representative scientific achievements and
discuss future challenges and directions for the pharmacological sciences in
China.
PMID- 28404615
TI - Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling.
AB - RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients
suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by
polymorphonuclear neutrophils, accumulates within ischemic myocardium and has
been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role
of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND
RESULTS: In different murine models of myocardial ischemia, myeloperoxidase
deficiency profoundly decreased vulnerability for ventricular tachycardia on
programmed right ventricular and burst stimulation and spontaneously as assessed
by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18
integrin-deficient (CD11b-/-) mice and intravenous myeloperoxidase infusion
revealed that neutrophil infiltration is a prerequisite for myocardial
myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo-/-)
mice showed less pronounced slowing and decreased heterogeneity of electric
conduction in the peri-infarct zone than wild-type mice. Expression of the redox
sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri
infarct area of wild-type compared with Mpo-/- mice. In isolated wild-type
cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2
incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte
networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase
dependent activation of matrix metalloproteinase 7. Moreover, Mpo-/- mice showed
decreased ventricular postischemic fibrosis reflecting reduced accumulation of
myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to
myofibroblast transdifferentiation by activation of p38 mitogen-activated protein
kinases resulting in upregulated collagen generation. In support of our
experimental findings, baseline myeloperoxidase plasma levels were independently
associated with a history of ventricular arrhythmias, sudden cardiac death, or
implantable cardioverter-defibrillator implantation in a cohort of 2622 stable
patients with an ejection fraction >35% undergoing elective diagnostic cardiac
evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of
postischemic myocardial remodeling and may evolve as a novel pharmacological
target for secondary disease prevention after myocardial ischemia.
PMID- 28404617
TI - Short term use of oral corticosteroids and related harms among adults in the
United States: population based cohort study.
AB - Objective To determine the frequency of prescriptions for short term use of oral
corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures)
associated with their use.Design Retrospective cohort study and self controlled
case series.Setting Nationwide dataset of private insurance claims.Participants
Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014.Main
outcome measures Rates of short term use of oral corticosteroids defined as less
than 30 days duration. Incidence rates of adverse events in corticosteroid users
and non-users. Incidence rate ratios for adverse events within 30 day and 31-90
day risk periods after drug initiation.Results Of 1 548 945 adults, 327 452
(21.1%) received at least one outpatient prescription for short term use of oral
corticosteroids over the three year period. Use was more frequent among older
patients, women, and white adults, with significant regional variation (all
P<0.001). The most common indications for use were upper respiratory tract
infections, spinal conditions, and allergies. Prescriptions were provided by a
diverse range of specialties. Within 30 days of drug initiation, there was an
increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval
3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87,
1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased
risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence
rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for
fracture; all P<0.001).Conclusion One in five American adults in a commercially
insured plan were given prescriptions for short term use of oral corticosteroids
during a three year period, with an associated increased risk of adverse events.
PMID- 28404618
TI - How to start a blog.
AB - Blogs that address issues of health and medical education run by clinical and
research teams can have a profound impact on how patients access and navigate
health information. Regularly updated websites are useful tools to facilitate two
way communication with a range of different audiences from patients to the
general public. They provide benefits of supporting patients to learn and self
manage their health, and to educate colleagues and disseminate research. This
article describes how to set up a blog, pointing out some simple style and
formatting considerations, usable methods and appropriate conduct for healthcare
professionals to engage with patients online.
PMID- 28404619
TI - Bilateral optic disc drusen mimicking papilloedema.
PMID- 28404621
TI - Longitudinal Risk of Adverse Events in Patients With Acute Kidney Injury After
Percutaneous Coronary Intervention: Insights From the National Cardiovascular
Data Registry.
AB - BACKGROUND: Acute kidney injury (AKI) remains a common complication after
percutaneous coronary intervention (PCI) and is associated with adverse in
hospital patient outcomes. The incidence of adverse events after hospital
discharge in patients having post-PCI AKI is poorly defined, and the relationship
between AKI and outcomes after hospital discharge remains understudied. METHODS
AND RESULTS: Using the National Cardiovascular Data Registry CathPCI registry, we
assessed the incidence of AKI among Medicare beneficiaries after PCI from 2004 to
2009 and subsequent post-discharge adverse events at 1 year. AKI was defined
using Acute Kidney Injury Network (AKIN) criteria. Adverse events included death,
myocardial infarction, bleeding, and recurrent kidney injury. Using Cox methods,
we determined the relationship between in-hospital AKI and risk of post-discharge
adverse events by AKIN stage. In a cohort of 453 475 elderly patients undergoing
PCI, 39 850 developed AKI (8.8% overall; AKIN stage 1, 85.8%; AKIN 2/3, 14.2%).
Compared with no AKI, in-hospital AKI was associated with higher post-discharge
hazard of death, myocardial infarction, or bleeding (AKIN 1: hazard ratio [HR],
1.53; confidence interval [CI], 1.49-1.56 and AKIN 2/3: HR, 2.13; CI, 2.01-2.26),
recurrent AKI (AKIN 1: HR, 1.70; CI, 1.64-1.76; AKIN 2/3: HR, 2.22; CI, 2.04
2.41), and AKI requiring dialysis (AKIN 1: HR, 2.59; CI, 2.29-2.92; AKIN 2/3: HR,
4.73; CI, 3.73-5.99). For each outcome, the highest incidence was within 30 days.
CONCLUSIONS: Post-PCI AKI is associated with increased risk of death, myocardial
infarction, bleeding, and recurrent renal injury after discharge. Post-PCI AKI
should be recognized as a significant risk factor not only for in-hospital
adverse events but also after hospital discharge.
PMID- 28404620
TI - Accumulation of RNA on chromatin disrupts heterochromatic silencing.
AB - Long noncoding RNAs (lncRNAs) play a conserved role in regulating gene
expression, chromatin dynamics, and cell differentiation. They serve as a
platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA
methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe
that heterochromatin is lost at transcribed regions in the absence of RNA
degradation. We show that heterochromatic RNAs are retained on chromatin, form
DNA:RNA hybrids, and need to be degraded by the Ccr4-Not complex or RNAi to
maintain heterochromatic silencing. The Ccr4-Not complex is localized to
chromatin independently of H3K9me and degrades chromatin-associated transcripts,
which is required for transcriptional silencing. Overexpression of
heterochromatic RNA, but not euchromatic RNA, leads to chromatin localization and
loss of silencing of a distant ade6 reporter in wild-type cells. Our results
demonstrate that chromatin-bound RNAs disrupt heterochromatin organization and
need to be degraded in a process of heterochromatin formation.
PMID- 28404622
TI - Choice of Stent for Percutaneous Coronary Intervention of Saphenous Vein Grafts.
AB - BACKGROUND: There are limited data on comparison of contemporary drug-eluting
stent (DES) platforms, previous generation DES, and bare-metal stents (BMS) for
percutaneous coronary intervention in saphenous vein grafts (SVG). We aimed to
assess clinical outcomes following percutaneous coronary intervention to SVG in
patients receiving bare-metal stents (BMS), first-generation DES, and newer
generation DES in a large unselected national data set from the BCIS (British
Cardiovascular Intervention Society). METHODS AND RESULTS: Patients undergoing
percutaneous coronary intervention to SVG in the United Kingdom from January 2006
to December 2013 were divided into 3 groups according to stent use: BMS, first
generation DES, and newer generation DES group. Study outcomes included in
hospital major adverse cardiovascular events, 30-day mortality, and 1-year
mortality. Patients (n=15 003) underwent percutaneous coronary intervention to
SVG in England and Wales during the study period. Of these, 38% received BMS, 15%
received first-generation DES, and 47% received second-generation DES. The rates
of in-hospital major adverse cardiovascular events were significantly lower in
patients treated with second-generation DES (odds ratio, 0.51; 95% confidence
interval, 0.38-0.68; P<0.001), but not with first-generation DES, compared with
BMS-treated patients. Similarly, 30-day mortality (odds ratio, 0.43; 95%
confidence interval, 0.32-0.59; P<0.001) and 1-year mortality (odds ratio, 0.60;
95% confidence interval, 0.51-0.71; P<0.001) were lower in patients treated with
second-generation DES, but not with first-generation DES, compared with the
patients treated with BMS. CONCLUSIONS: Patients receiving second-generation DES
for the treatment SVG disease have lower rates of in-hospital major adverse
cardiovascular events, 30-day mortality, and 1-year mortality, compared with
those receiving BMS.
PMID- 28404624
TI - Bypass Graft Failure: Changing What We Can, Accepting What We Cannot Change, and
Developing the Science to Know the Difference.
PMID- 28404623
TI - Fractional Flow Reserve-Guided Complete Revascularization Improves the Prognosis
in Patients With ST-Segment-Elevation Myocardial Infarction and Severe Nonculprit
Disease: A DANAMI 3-PRIMULTI Substudy (Primary PCI in Patients With ST-Elevation
Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only
or Complete Revascularization).
AB - BACKGROUND: The impact of disease severity on the outcome after complete
revascularization in patients with ST-segment-elevation myocardial infarction and
multivessel disease is uncertain. The objective of this post hoc study was to
evaluate the impact of number of diseased vessel, lesion location, and severity
of the noninfarct-related stenosis on the effect of fractional flow reserve
guided complete revascularization. METHODS AND RESULTS: In the DANAMI-3-PRIMULTI
study (Primary PCI in Patients With ST-Elevation Myocardial Infarction and
Multivessel Disease: Treatment of Culprit Lesion Only or Complete
Revascularization), we randomized 627 ST-segment-elevation myocardial infarction
patients to fractional flow reserve-guided complete revascularization or infarct
related percutaneous coronary intervention only. In patients with 3-vessel
disease, fractional flow reserve-guided complete revascularization reduced the
primary end point (all-cause mortality, reinfarction, and ischemia-driven
revascularization; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.17
0.64; P=0.001), with no significant effect in patients with 2-vessel disease (HR,
0.77; 95% CI, 0.47-1.26; P=0.29; P for interaction =0.046). A similar effect was
observed in patients with diameter stenosis >=90% of noninfarct-related arteries
(HR, 0.32; 95% CI, 0.18-0.62; P=0.001), but not in patients with less severe
lesions (HR, 0.72; 95% CI, 0.44-1.19; P=0.21; P for interaction =0.06). The
effect was most pronounced in patients with 3-vessel disease and noninfarct
related stenoses >=90%, and in this subgroup, there was a nonsignificant
reduction in the end point of mortality and reinfarction (HR, 0.32; 95% CI, 0.08
1.32; P=0.09). Proximal versus distal location did not influence the benefit from
complete revascularization. CONCLUSIONS: The benefit from fractional flow reserve
guided complete revascularization in ST-segment-elevation myocardial infarction
patients with multivessel disease was dependent on the presence of 3-vessel
disease and noninfarct diameter stenosis >=90% and was particularly pronounced in
patients with both of these angiographic characteristics. CLINICAL TRIAL
REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01960933.
PMID- 28404625
TI - Multivessel Revascularization and ST-Segment-Elevation Myocardial Infarction: Do
We Have the Complete Answer?
PMID- 28404626
TI - Adenosine Formed by CD73 on T Cells Inhibits Cardiac Inflammation and Fibrosis
and Preserves Contractile Function in Transverse Aortic Constriction-Induced
Heart Failure.
AB - BACKGROUND: Structural damage during heart failure development leads to increased
infiltration of leukocytes. Because purinergic signaling on immune cells may
impact on the inflammatory response, we evaluated the role of ecto-5'
nucleotidase (CD73) on the development of heart failure after transverse aortic
constriction (TAC) using global and T-cell-specific CD73-/- mice. METHODS AND
RESULTS: Leukocytes infiltrating the failing heart were analyzed by a multistep
enzymatic procedure over a period of 16 weeks using fluorescence-activated cell
sorting. TAC significantly enhanced the infiltration of leukocytes, especially T
cells. The fraction of CD73 expressing cells increased over time exclusively on
cytotoxic T cells, T-helper cells, and regulatory T cells. Cardiac function
significantly declined in T-cell-specific CD4-Cre+/-CD73flox/flox mice identical
to that observed in global CD73 mutants and was associated with enhanced fibrosis
(collagen, laminin, vimentin, periostin). Expression analysis by quantitative
reverse transcription polymerase chain reaction of extracellular purine degrading
enzymes and P1 and P2 receptors on T cells isolated from the injured heart
revealed profound upregulation of the enzymatic machinery for hydrolysis of
extracellular adenosine triphosphate and nicotinamide adenine dinucleotide, both
pathways converging in the formation of AMP and adenosine via CD73. Among the P1
receptors, only the A2a receptor was significantly upregulated after TAC. T cells
isolated from TAC-treated hearts show enhanced production of proinflammatory
cytokines (interleukin-3, interleukin-6, interleukin-13, interleukin-17,
macrophage inflammatory proteins-1alpha, and macrophage inflammatory proteins
1beta) when CD73 was lacking. CONCLUSIONS: Our data provide first evidence that
CD73 on T cells plays an important anti-inflammatory role in TAC-induced heart
failure, which is associated with antifibrotic activity and reduced production of
proinflammatory cytokines most likely by activation of the adenosine A2a
receptor.
PMID- 28404627
TI - Multiphasic Regulation of Systemic and Peripheral Organ Metabolic Responses to
Cardiac Hypertrophy.
AB - BACKGROUND: Reduced fat oxidation in hypertrophied hearts coincides with a shift
of carnitine palmitoyl transferase I from muscle to increased liver isoforms.
Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has
been shown to recapitulate the reduced fat oxidation and elevated atrial
natriuretic peptide message of cardiac hypertrophy. METHODS AND RESULTS: Because
of the potential for reduced fat oxidation to affect cardiac atrial natriuretic
peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic
metabolism in male C57BL/6 mice model of transverse aortic constriction in which
left ventricular hypertrophy occurred by 2 weeks without functional decline until
16 weeks (ejection fraction, -45.6%; fractional shortening, -22.6%). We report
the first evidence for initially improved glucose tolerance and insulin
sensitivity in response to 2 weeks transverse aortic constriction versus sham,
linked to enhanced insulin signaling in liver and visceral adipose tissue
(epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated
adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with
upregulated oxidative/thermogenic gene expression, and downregulated lipolysis
and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic
constriction, the metabolic profile reversed with impaired insulin sensitivity
and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and
heart, and downregulation of oxidative enzymes in brown adipose tissue and
oxidative and lipogenic genes in inguinal WAT. CONCLUSIONS: Changes in insulin
signaling, circulating natriuretic peptides and adipokines, and varied expression
of adipose genes associated with altered insulin response/glucose handling and
thermogenesis occurred prior to any functional decline in transverse aortic
constriction hearts. The findings demonstrate multiphasic responses in
extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning
providing potential metabolic benefits.
PMID- 28404628
TI - Simultaneous detection of decidual Th1/Th2 and NK1/NK2 immunophenotyping in
unknown recurrent miscarriage using 8-color flow cytometry with FSC/Vt extended
strategy.
AB - Th1/Th2 imbalance is considered as a mechanism for recurrent miscarriage. The
NK1/NK2 paradigm is hypothesised to play an important role in pregnancy. However,
few results showed simultaneous changes of these subsets in vivo in decidual
tissues. The present study aimed to detect the decidual mononuclear cells (dMo),
and the Th1/Th2, and NK1/NK2 paradigm simultaneously using multiparametric flow
cytometry (MFC) in unexplained recurrent miscarriages (URM). Mononuclear cells
were isolated from the decidual tissues of URM cases and early pregnant women.
The mononuclear cell percent was demonstrated by detecting the expression of CD3,
CD4, CD8, CD56, and CD16 extracellular markers, interferon (IFN)-gamma, and
interleukin (IL)-4 intracellular markers in live cells using 8-color flow
cytometry with forward scatter (FSC)/side scatter (SSC) and FSC/viability (Vt)
initial gating strategies, and the ratios of Th1/Th2 and decidual NK1
(dNK1)/decidual NK2 (dNK2) cells were compared between the subject groups. Two
initial gating strategies of the FSC/SSC or FSC/Vt, with central or extended
gating scales, were adapted, and there was no main effect or interaction for the
cell proportions, except for the type 1 and type 2 subsets in the FSC/Vt extended
gating strategy. There was no significant difference of the proportions of the
decidual T, dNK, NKT-like, Th, and Tc cells between the two groups. However, the
Th1/Th2 and dNK1/dNK2 ratios in the URM patients were higher compared with the
normal group when using the FSC/Vt extended gating strategy. The present study
provides means to detect Th1/Th2 and dNK1/dNK2 simultaneously in URM patients for
large sample investigations in the future.
PMID- 28404629
TI - BRaf signaling principles unveiled by large-scale human mutation analysis with a
rapid lentivirus-based gene replacement method.
AB - Rapid advances in genetics are linking mutations on genes to diseases at an
exponential rate, yet characterizing the gene-mutation-cell-behavior
relationships essential for precision medicine remains a daunting task. More than
350 mutations on small GTPase BRaf are associated with various tumors, and ~40
mutations are associated with the neurodevelopmental disorder cardio-facio
cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based
rapid gene replacement method to interrogate the physiopathology of BRaf and ~50
disease-linked BRaf mutants, including all CFC-linked mutants. Analysis of
simultaneous multiple patch-clamp recordings from 6068 pairs of rat neurons with
validation in additional mouse and human neurons and multiple learning tests from
1486 rats identified BRaf as the key missing signaling effector in the common
synaptic NMDA-R-CaMKII-SynGap-Ras-BRaf-MEK-ERK transduction cascade. Moreover,
the analysis creates the original big data unveiling three general features of
BRaf signaling. This study establishes the first efficient procedure that permits
large-scale functional analysis of human disease-linked mutations essential for
precision medicine.
PMID- 28404631
TI - Regulatory functions and chromatin loading dynamics of linker histone H1 during
endoreplication in Drosophila.
AB - Eukaryotic DNA replicates asynchronously, with discrete genomic loci replicating
during different stages of S phase. Drosophila larval tissues undergo
endoreplication without cell division, and the latest replicating regions
occasionally fail to complete endoreplication, resulting in underreplicated
domains of polytene chromosomes. Here we show that linker histone H1 is required
for the underreplication (UR) phenomenon in Drosophila salivary glands. H1
directly interacts with the Suppressor of UR (SUUR) protein and is required for
SUUR binding to chromatin in vivo. These observations implicate H1 as a critical
factor in the formation of underreplicated regions and an upstream effector of
SUUR. We also demonstrate that the localization of H1 in chromatin changes
profoundly during the endocycle. At the onset of endocycle S (endo-S) phase, H1
is heavily and specifically loaded into late replicating genomic regions and is
then redistributed during the course of endoreplication. Our data suggest that
cell cycle-dependent chromosome occupancy of H1 is governed by several
independent processes. In addition to the ubiquitous replication-related
disassembly and reassembly of chromatin, H1 is deposited into chromatin through a
novel pathway that is replication-independent, rapid, and locus-specific. This
cell cycle-directed dynamic localization of H1 in chromatin may play an important
role in the regulation of DNA replication timing.
PMID- 28404630
TI - miR-424(322)/503 is a breast cancer tumor suppressor whose loss promotes
resistance to chemotherapy.
AB - The female mammary gland is a very dynamic organ that undergoes continuous tissue
remodeling during adulthood. Although it is well established that the number of
menstrual cycles and pregnancy (in this case transiently) increase the risk of
breast cancer, the reasons are unclear. Growing clinical and experimental
evidence indicates that improper involution plays a role in the development of
this malignancy. Recently, we described the miR-424(322)/503 cluster as an
important regulator of mammary epithelial involution after pregnancy. Here,
through the analysis of ~3000 primary tumors, we show that miR-424(322)/503 is
commonly lost in a subset of aggressive breast cancers and describe the genetic
aberrations that inactivate its expression. Furthermore, through the use of a
knockout mouse model, we demonstrate for the first time that loss of miR
424(322)/503 promotes breast tumorigenesis in vivo. Remarkably, we found that
loss of miR-424(322)/503 promotes chemoresistance due to the up-regulation of two
of its targets: BCL-2 and insulin-like growth factor-1 receptor (IGF1R).
Importantly, targeted therapies blocking the aberrant activity of these targets
restore sensitivity to chemotherapy. Overall, our studies reveal miR-424(322)/503
as a tumor suppressor in breast cancer and provide a link between mammary
epithelial involution, tumorigenesis, and the phenomenon of chemoresistance.
PMID- 28404632
TI - Transcriptional integration of paternal and maternal factors in the Arabidopsis
zygote.
AB - In many plants, the asymmetric division of the zygote sets up the apical-basal
axis of the embryo. Unlike animals, plant zygotes are transcriptionally active,
implying that plants have evolved specific mechanisms to control transcriptional
activation of patterning genes in the zygote. In Arabidopsis, two pathways have
been found to regulate zygote asymmetry: YODA (YDA) mitogen-activated protein
kinase (MAPK) signaling, which is potentiated by sperm-delivered mRNA of the
SHORT SUSPENSOR (SSP) membrane protein, and up-regulation of the patterning gene
WOX8 by the WRKY2 transcription factor. How SSP/YDA signaling is transduced into
the nucleus and how these pathways are integrated have remained elusive. Here we
show that paternal SSP/YDA signaling directly phosphorylates WRKY2, which in turn
leads to the up-regulation of WOX8 transcription in the zygote. We further
discovered the transcription factors HOMEODOMAIN GLABROUS11/12 (HDG11/12) as
maternal regulators of zygote asymmetry that also directly regulate WOX8
transcription. Our results reveal a framework of how maternal and paternal
factors are integrated in the zygote to regulate embryo patterning.
PMID- 28404633
TI - IL-7Ralpha Expression Regulates Murine Dendritic Cell Sensitivity to Thymic
Stromal Lymphopoietin.
AB - Thymic stromal lymphopoietin (TSLP) and IL-7 are related cytokines that mediate
growth and differentiation events in the immune system. They signal through IL
7Ralpha-containing receptors. Target cells of TSLP in Th2 responses include CD4 T
cells and dendritic cells (DCs). Although it has been reported that expression of
TSLP receptor (TSLPR) on CD4 T cells is required for OVA-induced lung
inflammation, DCs have also been shown to be target cells of TSLP. In this study,
we show that murine ex vivo splenic DCs are unresponsive to TSLP, as they fail to
phosphorylate STAT5, but in vitro overnight culture, especially in presence of IL
4, renders DCs responsive to both TSLP and IL-7. This induced responsiveness is
accompanied by dramatic upregulation of IL-7Ralpha on DCs with little change in
expression of TSLPR or of gammac In splenic DCs, the induction of IL-7Ralpha
occurs mainly in CD8- DCs. In vivo, we found that IL-4 has a differential
regulatory role on expression of IL-7Ralpha depending on the cell type; IL-4
decreases IL-7Ralpha expression on CD4 T cells whereas it upregulates the
expression on DCs. Our results indicate that the induction of IL-7Ralpha
expression on DCs is critical for TSLP responsiveness and that IL-4 can
upregulate IL-7Ralpha on DCs.
PMID- 28404634
TI - Mucosal IgM Antibody with d-Mannose Affinity in Fugu Takifugu rubripes Is
Utilized by a Monogenean Parasite Heterobothrium okamotoi for Host Recognition.
AB - How parasites recognize their definitive hosts is a mystery; however, parasitism
is reportedly initiated by recognition of certain molecules on host surfaces.
Fish ectoparasites make initial contact with their hosts at body surfaces, such
as skin and gills, which are covered with mucosa that are similar to those of
mammalian guts. Fish are among the most primitive vertebrates with immune systems
that are equivalent to those in mammals, and they produce and secrete IgM into
mucus. In this study, we showed that the monogenean parasite Heterobothrium
okamotoi utilizes IgM to recognize its host, fugu Takifugu rubripes Oncomiracidia
are infective larvae of H. okamotoi that shed their cilia and metamorphose into
juveniles when exposed to purified d-mannose-binding fractions from fugu mucus.
Using liquid chromatography-tandem mass spectrometry analysis, proteins contained
in the fraction were identified as d-mannose-specific IgM with two d-mannose
binding lectins. However, although deciliation was significantly induced by IgM
and was inhibited by d-mannose or a specific Ab against fugu IgM, other lectins
had no effect, and IgM without d-mannose affinity induced deciliation to a
limited degree. Subsequent immunofluorescent staining experiments showed that
fugu d-mannose-specific IgM binds ciliated epidermal cells of oncomiracidium.
These observations suggest that deciliation is triggered by binding of fugu IgM
to cell surface Ags via Ag binding sites. Moreover, concentrations of d-mannose
binding IgM in gill mucus were sufficient to induce deciliation in vitro,
indicating that H. okamotoi parasites initially use host Abs to colonize host
gills.
PMID- 28404635
TI - A Novel miR-24-TCF1 Axis in Modulating Effector T Cell Responses.
AB - miR-23~27~24 was recently implicated in restricting Th2 immunity, as well as the
differentiation and function of other effector T cell lineages. Interestingly,
miR-24, unlike other family members, actually promotes Th1 and Th17 responses. In
this article, we show that miR-24 drives the production of IFN-gamma and IL-17 in
T cells at least in part through targeting TCF1, a transcription factor known for
its role in limiting Th1 and Th17 immunity. Surprisingly, whereas TCF1 was
previously shown to promote Th2 responses through inducing GATA3, enforced TCF1
expression in miR-24-overexpressing T cells led to further downregulation of IL-4
and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity
cannot be attributed to TCF1 repression by miR-24. Together, our data demonstrate
a novel miR-24-TCF1 pathway in controlling effector cytokine production by T
cells and further suggest miR-24 could function as a key upstream molecule
regulating TCF1-mediated immune responses.
PMID- 28404637
TI - Surfactant inhibits ATP-induced release of interleukin-1beta via nicotinic
acetylcholine receptors.
AB - Interleukin (IL)-1beta is a potent pro-inflammatory cytokine of innate immunity
involved in host defense. High systemic IL-1beta levels, however, cause life
threatening inflammatory diseases, including systemic inflammatory response
syndrome. In response to various danger signals, the pro-form of IL-1beta is
synthesized and stays in the cytoplasm unless a second signal, such as
extracellular ATP, activates the inflammasome, which enables processing and
release of mature IL-1beta. As pulmonary surfactant is known for its anti
inflammatory properties, we hypothesize that surfactant inhibits ATP-induced
release of IL-1beta. Lipopolysaccharide-primed monocytic U937 cells were
stimulated with an ATP analog in the presence of natural or synthetic surfactant
composed of recombinant surfactant protein (rSP)-C,
palmitoylphosphatidylglycerol, and dipalmitoylphosphatidylcholine (DPPC). Both
surfactant preparations dose-dependently inhibited IL-1beta release from U937
cells. DPPC was the active constituent of surfactant, whereas rSP-C and
palmitoylphosphatidylglycerol were inactive. DPPC was also effective in primary
mononuclear leukocytes isolated from human blood. Experiments with nicotinic
antagonists, siRNA technology, and patch-clamp experiments suggested that
stimulation of nicotinic acetylcholine receptors (nAChRs) containing subunit
alpha9 results in a complete inhibition of the ion channel function of ATP
receptor, P2X7. In conclusion, the surfactant constituent, DPPC, efficiently
inhibits ATP-induced inflammasome activation and maturation of IL-1beta in human
monocytes by a mechanism involving nAChRs.
PMID- 28404636
TI - Antibody Distance from the Cell Membrane Regulates Antibody Effector Mechanisms.
AB - Immunotherapy using mAbs, such as rituximab, is an established means of treating
hematological malignancies. Abs can elicit a number of mechanisms to delete
target cells, including complement-dependent cytotoxicity, Ab-dependent cellular
cytotoxicity, and Ab-dependent cellular phagocytosis. The inherent properties of
the target molecule help to define which of these mechanisms are more important
for efficacy. However, it is often unclear why mAb binding to different epitopes
within the same target elicits different levels of therapeutic activity. To
specifically address whether distance from the target cell membrane influences
the aforementioned effector mechanisms, a panel of fusion proteins consisting of
a CD20 or CD52 epitope attached to various CD137 scaffold molecules was
generated. The CD137 scaffold was modified through the removal or addition of
cysteine-rich extracellular domains to produce a panel of chimeric molecules that
held the target epitope at different distances along the protein. It was shown
that complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity
favored a membrane-proximal epitope, whereas Ab-dependent cellular phagocytosis
favored an epitope positioned further away. These findings were confirmed using
reagents targeting the membrane-proximal or -distal domains of CD137 itself
before investigating these properties in vivo, where a clear difference in the
splenic clearance of transfected tumor cells was observed. Together, this work
demonstrates how altering the position of the Ab epitope is able to change the
effector mechanisms engaged and facilitates the selection of mAbs designed to
delete target cells through specific effector mechanisms and provide more
effective therapeutic agents.
PMID- 28404638
TI - Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free
fatty acids.
AB - Lipid accumulation is a pathological feature of every type of kidney injury.
Despite this striking histological feature, physiological accumulation of lipids
in the kidney is poorly understood. We studied whether the accumulation of lipids
in the fasted kidney are derived from lipoproteins or NEFAs. With overnight
fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and
glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney
uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a beta
adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the
kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose
triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36
mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor,
increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by
inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL
deletion. Despite the increase in CD36 expression with fasting, genetic loss of
CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data
demonstrate that fasting-induced triglyceride accumulation in the kidney
correlates with the plasma concentrations of NEFAs, but is not due to uptake of
lipoprotein lipids and does not involve the fatty acid transporter, CD36.
PMID- 28404639
TI - Cholesterol crystallization within hepatocyte lipid droplets and its role in
murine NASH.
AB - We recently reported that cholesterol crystals form in hepatocyte lipid droplets
(LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned
WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%,
0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led
to cholesterol loading of the liver, but not of adipose tissue, resulting in
fibrosing steatohepatitis at a dietary cholesterol concentration of >=0.5%,
whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic
cholesterol crystals and crown-like structures also developed at a dietary
cholesterol concentration >=0.5%. Crown-like structures consisted of activated
Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which
surrounded and processed cholesterol crystal-containing remnant LDs of dead
hepatocytes. The KCs processed LDs at the center of crown-like structures in the
extracellular space by lysosomal enzymes, ultimately transforming into lipid
laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they
developed cholesterol crystals in LD membranes, which caused activation of THP1
cells (macrophages) grown in coculture; upregulation of TNF-alpha, NLRP3, and
interleukin 1beta (IL1beta) mRNA; and secretion of IL-1beta. In conclusion,
cholesterol crystals form on the LD membrane of hepatocytes and cause activation
and cholesterol loading of KCs that surround and process these LDs by lysosomal
enzymes.
PMID- 28404640
TI - Comprehensive evaluation of the bactericidal activities of free bile acids in the
large intestine of humans and rodents.
AB - In addition to functioning as detergents that aid digestion of dietary lipids in
the intestine, some bile acids have been shown to exhibit antimicrobial activity.
However, detailed information on the bactericidal activities of the diverse
molecular species of bile acid in humans and rodents is largely unknown. Here, we
investigated the toxicity of 14 typical human and rodent free bile acids (FBAs)
by monitoring intracellular pH, membrane integrity, and viability of a human
intestinal bacterium, Bifidobacterium breve Japan Collection of Microorganisms
(JCM) 1192T, upon exposure to these FBAs. Of all FBAs evaluated, deoxycholic acid
(DCA) and chenodeoxycholic acid displayed the highest toxicities. Nine FBAs
common to humans and rodents demonstrated that alpha-hydroxy-type bile acids are
more toxic than their oxo-derivatives and beta-hydroxy-type epimers. In five
rodent-specific FBAs, beta-muricholic acid and hyodeoxycholic acid showed
comparable toxicities at a level close to DCA. Similar trends were observed for
the membrane-damaging effects and bactericidal activities to Blautia coccoides
JCM 1395T and Bacteroides thetaiotaomicron DSM 2079T, commonly represented in the
human and rodent gut microbiota. These findings will help us to determine the
fundamental properties of FBAs and better understand the role of FBAs in the
regulation of gut microbiota composition.
PMID- 28404642
TI - Squeezing out in a "tug of war": The role of myosin in neural stem cell
delamination.
AB - Neural stem cells or neuroblasts in the Drosophila melanogaster embryo delaminate
as single cells from the embryonic epidermis to give rise to the nervous system.
Using this accessible system to examine the molecular mechanisms of cell
ingression at a high temporal and spatial resolution, in this issue, Simoes et
al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608038) reveal that
myosin-driven anisotropic junction loss and apical constriction are the main
drivers of this process.
PMID- 28404641
TI - NLRP3 inflammasome as a novel target for docosahexaenoic acid metabolites to
abrogate glomerular injury.
AB - The nucleotide-binding oligomerization domain-like receptor containing pyrin
domain 3 (NLRP3) inflammasome has been implicated in podocyte injury and
glomerular sclerosis during hyperhomocysteinemia (hHcys). However, it remains
unclear whether the NLRP3 inflammasome can be a therapeutic target for treatment
of hHcys-induced kidney injury. Given that DHA metabolites-resolvins have potent
anti-inflammatory effects, the present study tested whether the prototype,
resolvin D1 (RvD1), and 17S-hydroxy DHA (17S-HDHA), an intermediate product,
abrogate hHcys-induced podocyte injury by targeting the NLRP3 inflammasome. In
vitro, confocal microscopy demonstrated that 17S-HDHA (100 nM) and RvD1 (60 nM)
prevented Hcys-induced formation of NLRP3 inflammasomes, as shown by reduced
colocalization of NLRP3 with apoptosis-associated speck-like protein containing a
caspase recruitment domain (ASC) or caspase-1. Both DHA metabolites inhibited
Hcys-induced caspase-1 activation and interleukin-1beta production. However, DHA
had no significant effect on these Hcys-induced changes in podocytes. In vivo,
DHA lipoxygenase metabolites substantially inhibited podocyte NLRP3 inflammasome
formation and activation and consequent glomerular sclerosis in mice with hHcys.
Mechanistically, RvD1 and 17S-HDHA were shown to suppress Hcys-induced formation
of lipid raft redox signaling platforms and subsequent O2.- production in
podocytes. It is concluded that inhibition of NLRP3 inflammasome activation is
one of the important mechanisms mediating the beneficial action of RvD1 and 17S
HDHA on Hcys-induced podocyte injury and glomerular sclerosis.
PMID- 28404643
TI - The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote
aggrephagy.
AB - Autophagy-dependent clearance of ubiquitinated and aggregated proteins is
critical to protein quality control, but the underlying mechanisms are not well
understood. Here, we report the essential role of the BEACH (beige and Chediak
Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated
proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein
foci, and its loss causes accumulation of Ub proteins and the autophagy cargo
receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins
by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting
regions in the BEACH domain, promoting LC3C recruitment to ubiquitinated
proteins. Inactivation of LC3C or defective autophagy results in accumulation of
Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes
accumulation of p62 bodies in cortical and striatal neurons in the brain. These
data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal
of Ub proteins, and provide important insights into CAMRQ2 syndrome, a WDR81
related developmental disorder.
PMID- 28404645
TI - IRP2 as a potential modulator of cell proliferation, apoptosis and prognosis in
nonsmall cell lung cancer.
AB - IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which is critical
to intracellular iron homeostasis and which relates to the rate of cellular
proliferation. IREB2 lies in a lung cancer susceptibility locus. The aims were to
assess 1) the relationship between iron loading, cell proliferation and IRP2
expression in lung cancer; 2) the potential of iron related pathways as
therapeutic targets; and 3) the relevance of IRP2 in operated lung cancer
patients.Cells of two nonsmall cell cancer (NSCLC) lines and primary bronchial
epithelial cells (PBECs) were cultured with and without iron; and proliferation,
apoptosis and migration were assessed. Reverse transcriptase PCR and Western blot
were used to assess expression of iron homeostasis genes/proteins. Iron chelation
and knockdown of IREB2 were used in vitro to explore therapeutics. A cohort of
operated NSCLC patients was studied for markers of systemic iron status, tumour
IRP2 staining and survival.Iron loading caused cell proliferation in cancer cell
lines, which were less able to regulate IREB2 expression than PBECs. Iron
chelation resulted in a return of proliferation rates to baseline levels;
knockdown of IREB2 had a similar effect. IRP2-positive tumours were larger
(p=0.045) and higher percentage staining related to poorer survival
(p=0.079).Loss of iron regulation represents a poor prognostic marker in lung
cancer.
PMID- 28404644
TI - Preprotein mature domains contain translocase targeting signals that are
essential for secretion.
AB - Secretory proteins are only temporary cytoplasmic residents. They are typically
synthesized as preproteins, carrying signal peptides N-terminally fused to their
mature domains. In bacteria secretion largely occurs posttranslationally through
the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane,
signal peptides are cleaved off and mature domains reach their destinations and
fold. Targeting to the translocase is mediated by signal peptides. The role of
mature domains in targeting and secretion is unclear. We now reveal that mature
domains harbor their own independent targeting signals (mature domain targeting
signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D
hydrophobic stretches that become available because of the unstructured states of
targeting-competent preproteins. Their receptor site on the cytoplasmic face of
the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to
the signal peptide cleft. Both the preprotein MTSs and their receptor site on
SecA are essential for protein secretion. Evidently, mature domains have their
own previously unsuspected distinct roles in preprotein targeting and secretion.
PMID- 28404646
TI - Efficacy of Pseudomonas aeruginosa eradication regimens in bronchiectasis.
PMID- 28404647
TI - Randomised comparison of needle aspiration and chest tube drainage in spontaneous
pneumothorax.
AB - Guidelines on spontaneous pneumothorax are contradictory as to intervention
between needle aspiration (NA) and chest tube drainage (CTD). Studies show poor
adherence to guidelines.Three Norwegian hospitals included patients with primary
(PSP) and secondary (SSP) spontaneous pneumothorax. Patients underwent NA or CTD
as the primary intervention. The main outcome was duration of hospital stay.
Secondary outcomes were immediate- and 1-week success rates and complications.127
patients were included, including 48 patients with SSP. 65 patients underwent NA,
63 patients CTD. Median (interquartile range) hospital stay was significantly
shorter for NA: 2.4 days (1.2-4.7 days), compared with CTD: 4.6 days (2.3-7.8
days) (p<0.001). The corresponding figures for the SSP subgroup were 2.54 days
(1.17-7.79 days) compared with 5.53 days (3.65-9.21 days) (p=0.049) for NA and
CTD, respectively. Immediate success rates were 69% for NA compared with 32% for
CTD (p<0.001). The positive effect of NA remained significant in sub-analyses for
SSP. There was no significant difference in 1-week success rates. Complications
occurred only during the CTD-treatment.Our study shows shorter hospital stay and
higher immediate success rates for NA compared with CTD. Subgroup analyses also
show clear benefits for NA for both PSP and SSP.
PMID- 28404648
TI - Lung volumes predict survival in patients with chronic lung allograft
dysfunction.
AB - Identification of disease phenotypes might improve the understanding of patients
with chronic lung allograft dysfunction (CLAD). The aim of the study was to
assess the impact of pulmonary restriction and air trapping by lung volume
measurements at the onset of CLAD.A total of 396 bilateral lung transplant
recipients were analysed. At onset, CLAD was further categorised based on
plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung
capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an
increased ratio of residual volume to total lung capacity. Outcome was survival
after CLAD onset. Patients with insufficient clinical information were excluded
(n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients
with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse
survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were
associated with increased mortality when controlling for multiple confounding
variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI
1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to
identify patients with combined phenotypes.Measurement of lung volumes in the
long-term follow-up of lung transplant recipients allows the identification of
patients who are at risk for worse outcome and warrant special consideration.
PMID- 28404649
TI - The microbiome in respiratory medicine: current challenges and future
perspectives.
AB - The healthy lung has previously been considered to be a sterile organ because
standard microbiological culture techniques consistently yield negative results.
However, culture-independent techniques report that large numbers of
microorganisms coexist in the lung. There are many unknown aspects in the field,
but available reports show that the lower respiratory tract microbiota: 1) is
similar in healthy subjects to the oropharyngeal microbiota and dominated by
members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows
changes in smokers and well-defined differences in chronic respiratory diseases,
although the temporal and spatial kinetics of these changes are only partially
known; and 3) shows relatively abundant non-cultivable bacteria in chronic
obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and
bronchiectasis, with specific patterns for each disease. In all of these
diseases, a loss of diversity, paralleled by an over-representation of
Proteobacteria (dysbiosis), has been related to disease severity and
exacerbations. However, it is unknown whether dysbiosis is a cause or a
consequence of the damage to bronchoalveolar surfaces.Finally, little is known
about bacterial functionality and the interactions between viruses, fungi and
bacteria. It is expected that future research in bacterial gene expressions,
metagenomics longitudinal analysis and host-microbiome animal models will help to
move towards targeted microbiome interventions in respiratory diseases.
PMID- 28404650
TI - Identification of a novel crizotinib-sensitive BCL11A-ALK gene fusion in a
nonsmall cell lung cancer patient.
PMID- 28404651
TI - Resistance profile of drugs composing the "shorter" regimen for multidrug
resistant tuberculosis in Brazil, 2000-2015.
PMID- 28404652
TI - Obstructive sleep apnoea as a risk factor for osteopenia and osteoporosis in the
male population: further data and comments.
PMID- 28404653
TI - Oropharyngeal dysphagia: when swallowing disorders meet respiratory diseases.
PMID- 28404654
TI - Physiology of chronic lung allograft dysfunction: back to the future?
PMID- 28404655
TI - Spontaneous pneumothorax: stop chest tube as first-line therapy.
PMID- 28404656
TI - The Art of Breathing: Oxygen.
PMID- 28404657
TI - Predicting and Reducing Driving Mishaps Among Drivers With Type 1 Diabetes.
AB - OBJECTIVE: Two aims of this study were to develop and validate A) a metric to
identify drivers with type 1 diabetes at high risk of future driving mishaps and
B) an online intervention to reduce mishaps among high-risk drivers. RESEARCH
DESIGN AND METHODS: To achieve aim A, in study 1, 371 drivers with type 1
diabetes from three U.S. regions completed a series of established questionnaires
about diabetes and driving. They recorded their driving mishaps over the next 12
months. Questionnaire items that uniquely discriminated drivers who did and did
not have subsequent driving mishaps were assembled into the Risk Assessment of
Diabetic Drivers (RADD) scale. In study 2, 1,737 drivers with type 1 diabetes
from all 50 states completed the RADD online. Among these, 118 low-risk (LR) and
372 high-risk (HR) drivers qualified for and consented to participate in a 2
month treatment period followed by 12 monthly recordings of driving mishaps. To
address aim B, HR participants were randomized to receive either routine care
(RC) or the online intervention "DiabetesDriving.com" (DD.com). Half of the
DD.com participants received a motivational interview (MI) at the beginning and
end of the treatment period to boost participation and efficacy. All of the LR
participants were assigned to RC. In both studies, the primary outcome variable
was driving mishaps. RESULTS: Related to aim A, in study 1, the RADD demonstrated
61% sensitivity and 75% specificity. Participants in the upper third of the RADD
distribution (HR), compared with those in the lower third (LR), reported 3.03 vs.
0.87 mishaps/driver/year, respectively (P < 0.001). In study 2, HR and LR
participants receiving RC reported 4.3 and 1.6 mishaps/driver/year, respectively
(P < 0.001). Related to aim B, in study 2, MIs did not enhance participation or
efficacy, so the DD.com and DD.com + MI groups were combined. DD.com participants
reported fewer hypoglycemia-related driving mishaps than HR participants
receiving RC (P = 0.01), but more than LR participants receiving RC, reducing the
difference between the HR and LR participants receiving RC by 63%. HR drivers
differed from LR drivers at baseline across a variety of hypoglycemia and driving
parameters. CONCLUSIONS: The RADD identified higher-risk drivers, and
identification seemed relatively stable across time, samples, and procedures.
This 11-item questionnaire could inform patients at higher risk, and their
clinicians, that they should take preventive steps to reduce driving mishaps,
which was accomplished in aim B using DD.com.
PMID- 28404658
TI - Association of Glycemic Variability in Type 1 Diabetes With Progression of
Microvascular Outcomes in the Diabetes Control and Complications Trial.
AB - OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the
beneficial effects of intensive versus conventional therapy on the development
and progression of microvascular complications of type 1 diabetes. These
beneficial effects were almost completely explained by the difference between
groups in the levels of HbA1c, which in turn were associated with the risk of
these complications. We assessed the association of glucose variability within
and between quarterly 7-point glucose profiles with the development and
progression of retinopathy, nephropathy, and cardiovascular autonomic neuropathy
during the DCCT. RESEARCH DESIGN AND METHODS: Measures of variability included
the within-day and updated mean (over time) of the SD, mean amplitude of glycemic
excursions (MAGE), and M-value, and the longitudinal within-day, between-day, and
total variances. Imputation methods filled in the 16.3% of expected glucose
values that were missing. RESULTS: Cox proportional hazards models assessed the
association of each measure of glycemic variation, as a time-dependent covariate,
with the risk of retinopathy and nephropathy, and a longitudinal logistic
regression model did likewise for cardiovascular autonomic neuropathy. Adjusted
for mean blood glucose, no measure of within-day variability was associated with
any outcome. Only the longitudinal mean M-value (over time) was significantly
associated with microalbuminuria when adjusted for the longitudinal mean blood
glucose and corrected for multiple tests using the Holm procedure. CONCLUSIONS:
Overall, within-day glycemic variability, as determined from quarterly glucose
profiles, does not play an apparent role in the development of microvascular
complications beyond the influence of the mean glucose.
PMID- 28404659
TI - Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular
Events and Mortality: Population-Based Cohort Study of 24,752 Metformin
Initiators.
AB - OBJECTIVE: We investigated the association of early achieved HbA1c level and
magnitude of HbA1c reduction with subsequent risk of cardiovascular events or
death in patients with type 2 diabetes who initiate metformin. RESEARCH DESIGN
AND METHODS: This was a population-based cohort study including all metformin
initiators with HbA1c tests in Northern Denmark, 2000-2012. Six months after
metformin initiation, we classified patients by HbA1c achieved (<6.5% or higher)
and by magnitude of HbA1c change from the pretreatment baseline. We used Cox
regression to examine subsequent rates of acute myocardial infarction, stroke, or
death, controlling for baseline HbA1c and other confounding factors. RESULTS: We
included 24,752 metformin initiators (median age 62.5 years, 55% males) with a
median follow-up of 2.6 years. The risk of a combined outcome event gradually
increased with rising levels of HbA1c achieved compared with a target HbA1c of
<6.5%: adjusted hazard ratio (HR) 1.18 (95% CI 1.07-1.30) for 6.5-6.99%, HR 1.23
(1.09-1.40) for 7.0-7.49%, HR 1.34 (1.14-1.57) for 7.5-7.99%, and HR 1.59 (1.37
1.84) for >=8%. Results were consistent for individual outcome events and robust
by age-group and other patient characteristics. A large absolute HbA1c reduction
from baseline also predicted outcome: adjusted HR 0.80 (0.65-0.97) for Delta =
4, HR 0.98 (0.80-1.20) for Delta = -3, HR 0.92 (0.78-1.08) for Delta = -2, and HR
0.99 (0.89-1.10) for Delta = -1 compared with no HbA1c change (Delta = 0).
CONCLUSIONS: A large initial HbA1c reduction and achievement of low HbA1c levels
within 6 months after metformin initiation are associated with a lower risk of
cardiovascular events and death in patients with type 2 diabetes.
PMID- 28404660
TI - The Genetic Requirements for Pentose Fermentation in Budding Yeast.
AB - Cells grow on a wide range of carbon sources by regulating substrate flow through
the metabolic network. Incoming sugar, for example, can be fermented or respired,
depending on the carbon identity, cell type, or growth conditions. Despite this
genetically-encoded flexibility of carbon metabolism, attempts to exogenously
manipulate central carbon flux by rational design have proven difficult,
suggesting a robust network structure. To examine this robustness, we
characterized the ethanol yield of 411 regulatory and metabolic mutants in
budding yeast. The mutants showed little variation in ethanol productivity when
grown on glucose or galactose, yet diversity was revealed during growth on
xylulose, a rare pentose not widely available in nature. While producing ethanol
at high yield, cells grown on xylulose produced ethanol at high yields, yet
induced expression of respiratory genes, and were dependent on them. Analysis of
mutants that affected ethanol productivity suggested that xylulose fermentation
results from metabolic overflow, whereby the flux through glycolysis is higher
than the maximal flux that can enter respiration. We suggest that this overflow
results from a suboptimal regulatory adjustment of the cells to this unfamiliar
carbon source.
PMID- 28404661
TI - Quantitative Assessment of Fat Levels in Caenorhabditis elegans Using Dark Field
Microscopy.
AB - The roundworm Caenorhabditis elegans is widely used as a model for studying
conserved pathways for fat storage, aging, and metabolism. The most broadly used
methods for imaging fat in C. elegans require fixing and staining the animal.
Here, we show that dark field images acquired through an ordinary light
microscope can be used to estimate fat levels in worms. We define a metric based
on the amount of light scattered per area, and show that this light scattering
metric is strongly correlated with worm fat levels as measured by Oil Red O (ORO)
staining across a wide variety of genetic backgrounds and feeding conditions.
Dark field imaging requires no exogenous agents or chemical fixation, making it
compatible with live worm imaging. Using our method, we track fat storage with
high temporal resolution in developing larvae, and show that fat storage in the
intestine increases in at least one burst during development.
PMID- 28404663
TI - Decoding Acute Myocardial Infarction among Patients on Dialysis.
PMID- 28404662
TI - SLC25 Family Member Genetic Interactions Identify a Role for HEM25 in Yeast
Electron Transport Chain Stability.
AB - The SLC25 family member SLC25A38 (Hem25 in yeast) was recently identified as a
mitochondrial glycine transporter that provides substrate to initiate
heme/hemoglobin synthesis. Mutations in the human SLC25A38 gene cause congenital
sideroblastic anemia. The full extent to which SLC25 family members coregulate
heme synthesis with other mitochondrial functions is not clear. In this study, we
surveyed 29 nonessential SLC25 family members in Saccharomyces cerevisiae for
their ability to support growth in the presence and absence of HEM25 Six SLC25
family members were identified that were required for growth or for heme
synthesis in cells lacking Hem25 function. Importantly, we determined that loss
of function of the SLC25 family member Flx1, which imports FAD into mitochondria,
together with loss of function of Hem25, resulted in inability to grow on media
that required yeast cells to supply energy using mitochondrial respiration. We
report that specific components of complexes of the electron transport chain are
decreased in the absence of Flx1 and Hem25 function. In addition, we show that
mitochondria from flx1Delta hem25Delta cells contain uncharacterized Cox2
containing high molecular weight aggregates. The functions of Flx1 and Hem25
provide a facile explanation for the decrease in heme level, and in specific
electron transport chain complex components.
PMID- 28404664
TI - New Insights into Podocyte Biology in Glomerular Health and Disease.
AB - Podocyte and glomerular research is center stage for the development of improved
preventive and therapeutic strategies for chronic progressive kidney diseases.
Held April 3-6, 2016, the 11th International Podocyte Conference took place in
Haifa and Jerusalem, Israel, where participants from all over the world presented
their work on new developments in podocyte research. In this review, we briefly
highlight the advances made in characterizing the mechanisms involved in podocyte
development, metabolism, acquired injury, and repair, including progress in
determining the roles of genetic variants and microRNA in particular, as well as
the advances made in diagnostic techniques and therapeutics.
PMID- 28404666
TI - Cardiovascular medication and intraocular pressure: results from the Gutenberg
Health Study.
AB - BACKGROUND: Intraocular pressure (IOP) is well known to be associated with blood
pressure and other cardiovascular risk factors. The influence of systemic
cardiovascular, in particular antihypertensive, medication on IOP is still
controversial. This study analyses the association between the use of
cardiovascular medications and IOP in a large European cohort. METHODS: The
Gutenberg Health Study is a population-based, prospective,observational cohort
study in mid-western Germany. IOP was measured using a non-contact tonometer. The
medication classes examined were peripheral vasodilators, diuretics, beta
blockers (overall, selective and non-selective), calcium channel blockers, renin
angiotensin blockers (overall, ACE inhibitors and angiotensin-receptor blockers),
nitrates, other antihypertensive medications, aspirin and statins. Subjects with
missing IOP values, topical IOP-lowering medication or previous ocular surgery
were excluded. In total, 13 527 subjects were enrolled in this study. Association
analyses between medication use and IOP were performed using multivariable linear
regression (p<0.0038). RESULTS: Neither selective nor non-selective systemic beta
blocker intake was associated with statistically significant lower IOP (-0.12 mm
Hg, p=0.054 and -0.70 mm Hg, p=0.037, respectively). IOP was not associated with
the use of ACE inhibitors after adjustment for body mass index, systolic blood
pressure and central corneal thickness (0.11 mm Hg; p=0.07). CONCLUSIONS: None of
the cardiovascular medications, in particular systemic beta-blocking agents,
showed an association with IOP in non-glaucoma subjects. The long-term drift
phenomenon of topical and systemic beta-blocker might explain this result. Our
results suggest that systemic beta-blockers have a negligible effect on IOP
reduction.
PMID- 28404667
TI - Distinct clinical characteristics of atypical optic neuritis with seronegative
aquaporin-4 antibody among Chinese patients.
AB - OBJECTIVE: To evaluate the clinical features and prognosis of atypical optic
neuritis (ON) with seronegative aquaporin-4 (AQP4) antibody in Chinese patients.
METHODS: All patients with first or relapsing ON were recruited from the Neuro
ophthalmology Department of the Chinese People's Liberation Army General Hospital
from January 2013 to December 2014 and assigned to one of three groups based on
diagnosis: atypical ON, typical ON and neuromyelitis optica spectrum disorder
(NMOSD)-ON. RESULTS: A total of 173 patients were included in the cohort. Fifty
patients (28.9%) were AQP4-Ab-positive and diagnosed with NMOSD-ON. Of 123
patients with seronegative AQP4-Ab, 37 (30.1%) patients had atypical ON, with
male predominance (25, 67.6%). The atypical ON group (compared with the typical
ON and NMOSD-ON groups) had a significantly lower female:male ratio (1:2.1 vs
1.8:1 and 9:1, respectively, p=0.001 and p<0.001), an older mean age of onset
(44.8, 13-71 years vs 36.9, 13-73 years and 36.2, 13-66 years, p=0.003 and
p=0.004), a lower rate of good (>=0.5) visual recovery (6.7% vs 79.8% and 30.9%,
p<0.001 and p<0.001) and (compared with the NMOSD-ON group) a lower recurrence
rate during a 2-year follow-up (29.3% vs 60%, p=0.009). However, none developed
to multiple sclerosis or neuromyelitis optica in the atypical ON group.
CONCLUSIONS: Atypical ON with seronegative AQP4-Ab had unique clinical features
in this Chinese cohort, including male predominance, an older age of onset, worse
visual acuity recovery and resistance to corticosteroid therapy. This condition
may be a distinct nosological entity with an unusual clinical and therapeutic
profile.
PMID- 28404668
TI - Nasalised distribution of peripapillary retinal nerve fibre layers in large
discs.
AB - BACKGROUND: To describe the distribution pattern of the peripapillary retinal
nerve fibre layer (RNFL) and major retinal vessel positions in patients with a
large disc. METHODS: The medical records of patients with a large disc and those
of normal controls were reviewed retrospectively. Comprehensive ophthalmic
examinations including Cirrus HD-optical coherence tomography (OCT) and
Heidelberg Retinal Tomography III (HRT III) were performed. We divided patients
into two groups (large disc group and control group) using an HRT-measured disc
size of 2.5 mm2 as a reference point. We extracted RNFL thicknesses at 256 points
with OCT, measured major retinal vessel positions and compared them between the
two groups. RESULTS: In total, 97 eyes of 97 patients were included, with 60
patients in the large disc group and 37 patients in the control group. All
patients were free of any glaucomatous change. We observed nasal shifting of the
second superior and inferior peaks in the large disc group compared with the
controls. The superior major temporal retinal arteries in patients with large
disc also showed significant nasal displacement. CONCLUSIONS: We could observe
nasalisation of the peripapillary RNFL and superior retinal artery in patients
with a large disc. As this phenomenon may lead to false positive results in OCT
based RNFL thickness maps, results from our study may help prevent misdiagnosis
of glaucoma and improve the sensitivity and specificity of glaucoma detection.
PMID- 28404669
TI - Retinopathy of prematurity: screening and treatment in Costa Rica.
AB - AIM: To determine the recent demographic data, risk factors and results of
retinopathy of prematurity (ROP) screening and treatment in Costa Rica. METHODS:
The medical records of all preterm infants meeting ROP screening criteria (<=34
weeks' gestational age (GA) or birth weight (BW) <=1750g, and those determined at
risk by neonatologists) in the national healthcare system, Costa Rica, January
2010-December 2014, were retrospectively reviewed. The numbers and percentages of
infants with ROP, risk factors, percentage of patients treated and treatment
outcomes were determined. Comparison is made with screening criteria and
literature reports of ROP incidence in other countries. RESULTS: The study
population included 3018 preterm infants. Overall, 585 patients (585/3018, 19.4%)
were found to have ROP. Of these, 15.4% (90 patients) required laser treatment,
and 53% of those requiring treatment had BW <1000g. Five babies requiring
treatment were >=32 weeks' GA but with BW <=1750g. Aggressive posterior disease
was found in nine patients, and two infants of those screened (2/3018, 0.07%)
suffered severe visual impairment during the 5-year study period. CONCLUSION: We
provide comprehensive data of ROP care in Costa Rica allowing assessment and
comparison of screening criteria and protocol.
PMID- 28404670
TI - Intravitreal dexamethasone implant in radiation-induced macular oedema.
AB - AIMS: To evaluate the efficacy and duration of activity of a single intravitreal
dexamethasone implant in patients affected by radiation maculopathy. METHODS:
Thirteen consecutive eyes of 13 patients affected by radiation maculopathy
secondary to eye irradiation for a primary uveal melanoma (Iodine-125
brachytherapy) and treated with a single intravitreal 0.7 mg dexamethasone
implant were retrospectively evaluated. Each patient underwent full
ophthalmological examination, including fluorescein angiography and spectral
domain optical coherence tomography (SD-OCT), even in en-face modality. Follow-up
was performed monthly over a 6-month period. RESULTS: At preinjection visit, the
median central subfield thickness (CST) by SD-OCT was 407 um (IQR, 357-524 um)
and the median best-corrected visual acuity (BCVA) was 61 ETDRS score (IQR, 54
67). The median gain of ETDRS letter at 1 month was 6.5 (IQR, 4-15) (p<0.01). The
median CST showed a reduction of 120 um (IQR, 62-134) (p<0.01). Further CST
reduction was reported at 2 months' follow-up, with CST stabilisation at 3 months
and maintenance of BCVA. At 4, 5 and 6 months' follow-up, all patients presented
progressive retinal thickening (p<0.01) and BCVA reduction (p<0.01). No side
effects were documented. CONCLUSION: Intravitreal dexamethasone implant reduces
macular oedema secondary to radiation maculopathy and also improved visual acuity
in a consistent proportion of patients. Signs of macular oedema recurrence may be
detected at a median of 4 months after injection.
PMID- 28404671
TI - Update on Antimicrobial Resistance in Clostridium difficile: Resistance
Mechanisms and Antimicrobial Susceptibility Testing.
AB - Oral antibiotics such as metronidazole, vancomycin and fidaxomicin are therapies
of choice for Clostridium difficile infection. Several important mechanisms for
C. difficile antibiotic resistance have been described, including the acquisition
of antibiotic resistance genes via the transfer of mobile genetic elements,
selective pressure in vivo resulting in gene mutations, altered expression of
redox-active proteins, iron metabolism, and DNA repair, as well as via biofilm
formation. This update summarizes new information published since 2010 on
phenotypic and genotypic resistance mechanisms in C. difficile and addresses
susceptibility test methods and other strategies to counter antibiotic resistance
of C. difficile.
PMID- 28404672
TI - Increased Tuberculosis Patient Mortality Associated with Mycobacterium
tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous
Drugs.
AB - Rapid molecular diagnostics have great potential to limit the spread of multidrug
resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR
TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium
tuberculosis genome that confer phenotypic drug resistance. However, there have
been few data published regarding the relationships between the detected M.
tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our
current ability to exploit the full potential of molecular diagnostics. We
analyzed clinical, microbiological, and sequencing data for 451 patients and
their clinical isolates collected in a multinational, observational cohort study
to determine if there was an association between M. tuberculosis resistance
mutations and patient mortality. The presence of an rrs 1401G mutation was
associated with significantly higher odds of patient mortality (adjusted odds
ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting
for relevant patient clinical characteristics and all other resistance mutations.
Further analysis of mutations, categorized by the associated resistance level,
indicated that the detection of mutations associated with high-level
fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95%
CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds
of patient mortality, even after accounting for clinical site, patient age,
reported smoking history, body mass index (BMI), diabetes, HIV, and all other
resistance mutations. Specific gyrA and rrs resistance mutations, associated with
high-level resistance, were associated with patient mortality as identified in
clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at
three high-burden clinical sites. These results have important implications for
the interpretation of molecular diagnostics, including identifying patients at
increased risk for mortality during treatment. (This study has been registered at
ClinicalTrials.gov under registration no. NCT02170441.).
PMID- 28404673
TI - Update on Malaria Diagnostics and Test Utilization.
AB - Malaria is a potentially life-threatening disease requiring rapid diagnosis and
treatment. Although microscopic examination of thick and thin blood films remains
the gold standard for laboratory diagnosis, rapid antigen tests and nucleic acid
amplification methods may also play a useful role in detection of acute
infection. This review discusses the advantages and disadvantages of the commonly
used diagnostic methods and provides important practice points for optimal
malaria test utilization.
PMID- 28404674
TI - Laboratory Diagnosis of Lassa Fever.
AB - Lassa virus remains an important cause of illness in West Africa and among the
travelers returning from this region with an acute febrile illness. The symptoms
of Lassa fever can be nonspecific and mimic those of other endemic infections,
especially early in illness, making a clinical diagnosis difficult; therefore,
laboratory testing is needed to confirm the diagnosis. An early identification of
Lassa fever is crucial for maximizing the benefit of available antiviral therapy,
as treatment efficacy rapidly decreases following the clinical onset of the
disease. This minireview provides an overview of the currently available
diagnostic tests for Lassa fever and their strengths and weaknesses.
PMID- 28404675
TI - Nucleic Acid Extraction from Residual Aptima Clinical Samples: Evaluation of
Automated Platform To Enhance Workflow.
PMID- 28404676
TI - Multicenter Performance Assessment of Carba NP Test.
AB - Eighty Gram-negative bacilli (54 Enterobacteriaceae and 26 nonfermenting Gram
negative bacilli) obtained from multiple institutions in the United States were
distributed in a blinded manner to seven testing laboratories to compare their
performance of a test for detection of carbapenemase production, the Carba NP
test. The Carba NP test was performed by all laboratories, following the Clinical
and Laboratory Standards Institute (CLSI) procedure. Site-versus-site comparisons
demonstrated a high level of consistency for the Carba NP assay, with just 3/21
site comparisons yielding a difference in sensitivity (P < 0.05). Previously
described limitations with blaOXA-48-like carbapenemases and blaOXA
carbapenemases associated with Acinetobacter baumannii were noted. Based on these
data, we demonstrate that the Carba NP test, when implemented with the
standardized CLSI methodology, provides reproducible results across multiple
sites for detection of carbapenemases.
PMID- 28404677
TI - Comparison of Whole-Genome Sequencing Methods for Analysis of Three Methicillin
Resistant Staphylococcus aureus Outbreaks.
AB - Whole-genome sequencing (WGS) can provide excellent resolution in global and
local epidemiological investigations of Staphylococcus aureus outbreaks. A
variety of sequencing approaches and analytical tools have been used; it is not
clear which is ideal. We compared two WGS strategies and two analytical
approaches to the standard method of SmaI restriction digestion pulsed-field gel
electrophoresis (PFGE) for typing S. aureus Forty-two S. aureus isolates from
three outbreaks and 12 reference isolates were studied. Near-complete genomes,
assembled de novo with paired-end and long-mate-pair (8 kb) libraries were first
assembled and analyzed utilizing an in-house assembly and analytical informatics
pipeline. In addition, paired-end data were assembled and analyzed using a
commercial software package. Single nucleotide variant (SNP) analysis was
performed using the in-house pipeline. Two assembly strategies were used to
generate core genome multilocus sequence typing (cgMLST) data. First, the near
complete genome data generated with the in-house pipeline were imported into the
commercial software and used to perform cgMLST analysis. Second, the commercial
software was used to assemble paired-end data, and resolved assemblies were used
to perform cgMLST. Similar isolate clustering was observed using SNP calling and
cgMLST, regardless of data assembly strategy. All methods provided more
discrimination between outbreaks than did PFGE. Overall, all of the evaluated WGS
strategies yielded statistically similar results for S. aureus typing.
PMID- 28404678
TI - Antifungal Susceptibility Testing of Aspergillus spp. by Using a Composite
Correlation Index (CCI)-Based Matrix-Assisted Laser Desorption Ionization-Time of
Flight Mass Spectrometry Method Appears To Not Offer Benefit over Traditional
Broth Microdilution Testing.
AB - Aspergillus spp. cause serious invasive lung infections, and Aspergillus
fumigatus is the most commonly encountered clinically significant species.
Voriconazole is considered to be the drug of choice for treating A. fumigatus
infections; however, rising resistance rates have been reported. We evaluated a
matrix-assisted laser desorption ionization-time of flight mass spectrometry
(MALDI-TOF MS)-based method for the differentiation between wild-type and non
wild-type isolates of 20 Aspergillus spp. (including 2 isolates of Aspergillus
ustus and 1 of Aspergillus calidoustus that were used as controls due their
intrinsic low azole susceptibility with respect to the in vitro response to
voriconazole). At 30 and 48 h of incubation, there was complete agreement between
Cyp51A sequence analysis, broth microdilution, and MALDI-TOF MS classification of
isolates as wild type or non-wild type. In this proof-of-concept study, we
demonstrated that MALDI-TOF MS can be used to accurately detect A. fumigatus
strains with reduced voriconazole susceptibility. However, rather than proving to
be a rapid and simple method for antifungal susceptibility testing, this
particular MS-based method showed no benefit over conventional testing methods.
PMID- 28404679
TI - Evaluation of a TaqMan Array Card for Detection of Central Nervous System
Infections.
AB - Infections of the central nervous system (CNS) are often acute, with significant
morbidity and mortality. Routine diagnosis of such infections is limited in
developing countries and requires modern equipment in advanced laboratories that
may be unavailable to a number of patients in sub-Saharan Africa. We developed a
TaqMan array card (TAC) that detects multiple pathogens simultaneously from
cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay
includes two parasites (Balamuthia mandrillaris and Acanthamoeba), six bacterial
pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria
meningitidis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Bartonella),
and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus,
mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein
Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also
includes human RNase P as a nucleic acid extraction control and an internal
manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS
TAC assay can test up to eight samples for all 21 agents within 2.5 h following
nucleic acid extraction. The assay was validated for linearity, limit of
detection, sensitivity, and specificity by using either live viruses (dengue,
mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya
viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for
eight different targets, whereas the CNS-TAC assay detected 37 positive samples
across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and
96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak
investigation and surveillance of suspected neurological disease.
PMID- 28404680
TI - Development and Validation of a Lateral Flow Immunoassay for Rapid Detection of
NDM-Producing Enterobacteriaceae.
AB - The global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are
often resistant to most, if not all, classes of antibiotics is a major public
health concern. The NDM-1 carbapenemase is among the most worrisome
carbapenemases given its rapid worldwide spread. We have developed and evaluated
a lateral flow immunoassay (LFIA) (called the NDM LFIA) for the rapid and
reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from
culture colonies. We evaluated the NDM LFIA using 175 reference enterobacterial
isolates with characterized beta-lactamase gene content and 74 nonduplicate
consecutive carbapenem-resistant clinical isolates referred for expertise to the
French National Reference Center (NRC) for Antibiotic Resistance during a 1-week
period (in June 2016). The reference collection included 55 non-carbapenemase
producers and 120 carbapenemase producers, including 27 NDM producers. All 27 NDM
like carbapenemase producers of the reference collection were correctly detected
in less than 15 min by the NDM LFIA, including 22 strains producing NDM-1, 2
producing NDM-4, 1 producing NDM-5, 1 producing NDM-7, and 1 producing NDM-9. All
non-NDM-1 producers gave a negative result with the NDM LFIA. No cross-reaction
was observed with carbapenemases (VIM, IMP, NDM, KPC, and OXA-48-like), extended
spectrum beta-lactamases (ESBLs) (TEM, SHV, and CTX-M), AmpCs (CMY-2, DHA-2, and
ACC-1), and oxacillinases (OXA-1, -2, -9, and -10). Similarly, among the 74
referred nonduplicate consecutive clinical isolates, all 7 NDM-like producers
were identified. Overall, the sensitivity and specificity of the assay were 100%
for NDM-like carbapenemase detection with strains cultured on agar. The NDM LFIA
was efficient, rapid, and easy to implement in the routine workflow of a clinical
microbiology laboratory for the confirmation of NDM-like carbapenemase-producing
Enterobacteriaceae.
PMID- 28404681
TI - Non-pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why
Is That?
AB - Pyrazinamide (PZA) is a key component for the effective treatment of drug
susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB).
pncA gene mutations are usually detected in a clear majority (>90%) of PZA
resistant strains but obviously not in all. Rapid and reliable PZA drug
susceptibility testing (DST) is critical whenever PZA is to be used in a
treatment regimen, not least for the treatment of MDRPZA-S TB. In this study, we
selected 26 PZA-resistant isolates reported to carry a wild-type pncA gene. To
confirm resistance, susceptibility testing was repeated using 100 mg/liter and
200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on
the 18 isolates that remained PZA resistant. Apart from the eight isolates
initially misclassified as PZA resistant, the retests identified three factors
responsible for the phenotype-genotype discrepancy: panD or rpsA mutations
identified by whole-genome sequencing (WGS) (n = 7), heteroresistance (n = 8),
and mixed populations with Mycobacterium avium (n = 3). Additionally, we
performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-R
clinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a
nonsynonymous pncA mutation (Thr87Met), whereas a nonsynonymous rpsA mutation was
found in 17 isolates. None of these isolates carried a nonsynonymous panD
mutation, while all 15 of the MDRPZA-R isolates harbored a nonsynonymous pncA
mutation. Our findings indicate that it is necessary to consider the occurrence
of panD mutations in PZA-resistant isolates, as well as heteroresistance, for the
development and evaluation of new molecular techniques to ensure high-quality DST
performance. The identification of nonsynonymous rpsA mutations in both PZA
susceptible and PZA-resistant isolates also implies that further studies are
needed in order to determine the role of rpsA in PZA resistance.
PMID- 28404682
TI - Comparison of ePlex Respiratory Pathogen Panel with Laboratory-Developed Real
Time PCR Assays for Detection of Respiratory Pathogens.
AB - Infections of the respiratory tract can be caused by a diversity of pathogens,
both viral and bacterial. Rapid microbiological diagnosis ensures appropriate
antimicrobial therapy as well as effective implementation of isolation
precautions. The ePlex respiratory pathogen panel (RP panel) is a novel molecular
biology-based assay, developed by GenMark Diagnostics, Inc. (Carlsbad, CA), to be
performed within a single cartridge for the diagnosis of 25 respiratory pathogens
(viral and bacterial). The objective of this study was to compare the performance
of the RP panel with those of laboratory-developed real-time PCR assays, using a
variety of previously collected clinical respiratory specimens. A total of 343
clinical specimens as well as 29 external quality assessment (EQA) specimens and
2 different Middle East respiratory syndrome coronavirus isolates have been
assessed in this study. The RP panel showed an agreement of 97.4% with the real
time PCR assay regarding 464 pathogens found in the clinical specimens. All
pathogens present in clinical samples and EQA samples with a threshold cycle (CT
) value of <30 were detected correctly using the RP panel. The RP panel detected
17 additional pathogens, 7 of which could be confirmed by discrepant testing. In
conclusion, this study shows excellent performance of the RP panel in comparison
to real-time PCR assays for the detection of respiratory pathogens. The ePlex
system provided a large amount of useful diagnostic data within a short time
frame, with minimal hands-on time, and can therefore potentially be used for
rapid diagnostic sample-to-answer testing, in either a laboratory or a
decentralized setting.
PMID- 28404683
TI - Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome.
AB - Acanthamoeba spp. and Balamuthia mandrillaris are causative agents of
granulomatous amoebic encephalitis (GAE), while Naegleria fowleri causes primary
amoebic meningoencephalitis (PAM). PAM is an acute infection that lasts a few
days, while GAE is a chronic to subacute infection that can last up to several
months. Here, we present a literature review of 86 case reports from 1968 to
2016, in order to explore the affinity of these amoebae for particular sites of
the brain, diagnostic modalities, treatment options, and disease outcomes in a
comparative manner.
PMID- 28404684
TI - The Immaculate Carbapenemase Study.
AB - Carbapenemase-producing organisms, or CPOs, are Gram-negative pathogens that
produce a transmissible carbapenemase and are typically resistant to most
(sometimes all) antibiotics. We now face a global CPO pandemic of high mortality.
In this issue of the Journal of Clinical Microbiology, Karlowsky et al. (J Clin
Microbiol 55:1638-1649, 2017, https://doi.org/10.1128/JCM.02316-16) report the
results of an extensive global surveillance study that provide much-needed
information that enhances our understanding of carbapenemase-producing
Enterobacteriaceae (CPE) and which will be valuable for the development of
improved strategies for CPE control and therapy of infections.
PMID- 28404685
TI - Rising maternal circulating GH during murine pregnancy suggests placental
regulation.
AB - Placenta-derived hormones including growth hormone (GH) in humans contribute to
maternal adaptation to pregnancy, and intermittent maternal GH administration
increases foetal growth in several species. Both patterns and abundance of
circulating GH are important for its activity, but their changes during pregnancy
have only been reported in humans and rats. The aim of the present study was to
characterise circulating profiles and secretory characteristics of GH in non
pregnant female mice and throughout murine pregnancy. Circulating GH
concentrations were measured in whole blood (2 MUL) collected every 10 min for 6
h in non-pregnant diestrus female C57Bl/6J mice (n = 9), and pregnant females at
day 8.5-9.5 (early pregnancy, n = 8), day 12.5-13.5 (mid-pregnancy, n = 7) and
day 17.5 after mating (late pregnancy, n = 7). Kinetics and secretory patterns of
GH secretion were determined by deconvolution analysis, while orderliness and
regularity of serial GH concentrations were calculated by approximate entropy
analysis. Circulating GH was pulsatile in all groups. Mean circulating GH and
total and basal GH secretion rates increased markedly from early to mid
pregnancy, and then remained elevated. Pulse frequency and pulsatile GH secretion
rate were similar between groups. The irregularity of GH pulses was higher in all
pregnant groups than that in non-pregnant mice. Increased circulating GH in
murine pregnancy is consistent with an important role for this hormone in
maternal adaptation to pregnancy and placental development. The timing of
increased basal secretion from mid-pregnancy, concurrent with the formation of
the chorioallantoic placenta and initiation of maternal blood flow through it,
suggests regulation of pituitary secretion by placenta-derived factors.
PMID- 28404686
TI - Propofol Anesthesia Is Reduced in Phospholipase C-Related Inactive Protein Type-1
Knockout Mice.
AB - The GABA type A receptor (GABAA-R) is a major target of intravenous anesthetics.
Phospholipase C-related inactive protein type-1 (PRIP-1) is important in GABAA-R
phosphorylation and membrane trafficking. In this study, we investigated the role
of PRIP-1 in general anesthetic action. The anesthetic effects of propofol,
etomidate, and pentobarbital were evaluated in wild-type and PRIP-1 knockout
(PRIP-1 KO) mice by measuring the latency and duration of loss of righting reflex
(LORR) and loss of tail-pinch withdrawal response (LTWR). The effect of
pretreatment with okadaic acid (OA), a protein phosphatase 1/2A inhibitor, on
propofol- and etomidate-induced LORR was also examined. PRIP-1 deficiency
provided the reduction of LORR and LTWR induced by propofol but not by etomidate
or pentobarbital, indicating that PRIP-1 could determine the potency of the
anesthetic action of propofol. Pretreatment with OA recovered the anesthetic
potency induced by propofol in PRIP-1 KO mice. OA injection enhanced
phosphorylation of cortical the GABAA-R beta3 subunit in PRIP-1 KO mice. These
results suggest that PRIP-1-mediated GABAA-R beta3 subunit phosphorylation might
be involved in the general anesthetic action induced by propofol but not by
etomidate or pentobarbital.
PMID- 28404687
TI - Selective Calcium-Dependent Inhibition of ATP-Gated P2X3 Receptors by
Bisphosphonate-Induced Endogenous ATP Analog ApppI.
AB - Pain is the most unbearable symptom accompanying primary bone cancers and bone
metastases. Bone resorptive disorders are often associated with hypercalcemia,
contributing to the pathologic process. Nitrogen-containing bisphosphonates
(NBPs) are efficiently used to treat bone cancers and metastases. Apart from
their toxic effect on cancer cells, NBPs also provide analgesia via poorly
understood mechanisms. We previously showed that NBPs, by inhibiting the
mevalonate pathway, induced formation of novel ATP analogs such as ApppI [1
adenosin-5'-yl ester 3-(3-methylbut-3-enyl) triphosphoric acid diester], which
can potentially be involved in NBP analgesia. In this study, we used the patch
clamp technique to explore the action of ApppI on native ATP-gated P2X receptors
in rat sensory neurons and rat and human P2X3, P2X2, and P2X7 receptors expressed
in human embryonic kidney cells. We found that although ApppI has weak agonist
activity, it is a potent inhibitor of P2X3 receptors operating in the nanomolar
range. The inhibitory action of ApppI was completely blocked in hypercalcemia
like conditions and was stronger in human than in rat P2X3 receptors. In
contrast, P2X2 and P2X7 receptors were insensitive to ApppI, suggesting a high
selectivity of ApppI for the P2X3 receptor subtype. NBP, metabolite isopentenyl
pyrophosphate, and endogenous AMP did not exert any inhibitory action, indicating
that only intact ApppI has inhibitory activity. Ca2+-dependent inhibition was
stronger in trigeminal neurons preferentially expressing desensitizing P2X3
subunits than in nodose ganglia neurons, which also express nondesensitizing P2X2
subunits. Altogether, we characterized previously unknown purinergic mechanisms
of NBP-induced metabolites and suggest ApppI as the endogenous pain inhibitor
contributing to cancer treatment with NBPs.
PMID- 28404688
TI - Brain Disposition of cis-para-Methyl-4-Methylaminorex (cis-4,4'-DMAR) and Its
Potential Metabolites after Acute and Chronic Treatment in Rats: Correlation with
Central Behavioral Effects.
AB - para-Methyl-4-methylaminorex (4,4'-DMAR) is a phenethylamine derivative with
psychostimulant activity whose abuse has been associated with several deaths and
a wide range of adverse effects. We recently validated a high-performance liquid
chromatography-tandem mass spectrometry method to measure the compound's
concentrations in plasma, and we applied it to describe the pharmacokinetic
properties of 4,4'-DMAR after a single dose in rats. In this study, we
investigated the brain disposition and metabolism of cis-4,4'-DMAR after
intraperitoneal injection as well as its central behavioral effects. Locomotor
activity increased after a single injection of 10 mg/kg, peaking at 2 hours and
disappearing at 5 hours; in these conditions, brain absorption was very rapid,
(tmax = 30-60 minutes) and large (brain-to-plasma ratio = 24); the half-life was
approximately 50 minutes. After 14 daily doses, the compound's effect on
locomotor activity was greater (approximately 20% compared with the effect after
the first dose), but not for pharmacokinetic reasons. Using high-resolution mass
spectrometry, we also identified four metabolites of cis-4,4'-DMAR in the plasma
and brain of treated rats. Semiquantitative analysis indicated low brain
permeability and very low brain concentrations, suggesting that these metabolites
do not contribute to central behavioral effects; however, the metabolite
originating from oxidation of the para-methyl group (M2) persisted in the plasma
longer and at higher concentrations than the parent molecule and could be used to
evaluate drug intake in human consumers. Finally, we describe the rewarding
effect of cis-4,4'-DMAR in the conditioning place preference test, suggesting a
high risk of addiction in humans.
PMID- 28404689
TI - Methoxyluteolin Inhibits Neuropeptide-stimulated Proinflammatory Mediator Release
via mTOR Activation from Human Mast Cells.
AB - Mast cells (MCs) are critical for allergic reactions but are also important in
inflammatory processes. Stimulation by neuropeptides, such as substance P (SP)
and neurotensin (NT), leads to release of preformed molecules stored in numerous
MC secretory granules and newly synthesized proinflammatory mediators, including
tumor necrosis factor, C-X-C motif chemokine ligand 8, and vascular endothelial
growth factor. Here, we investigate the role of mammalian target of rapamycin
(mTOR) signaling in the stimulation of cultured human LAD2 MCs by NT or SP, as
well as the inhibitory effect of the natural flavonoids 3',4',5,7
tetrahydroxyflavone (luteolin) and its novel structural analog 3',4',5,7
tetramethoxyflavone (methoxyluteolin). Stimulation by NT (10 MUM) or SP (1 MUM)
increases (P < 0.0001) gene expression (after 6 hours) and release (after 24
hours) of tumor necrosis factor, C-X-C motif chemokine ligand 8, and vascular
endothelial growth factor. This occurs via activation of both mTOR complexes, as
denoted by the increased phosphorylated (p) protein levels (P < 0.0001) of the
downstream mTORC1 substrate pp70S6KThr389 and mTORC2 component pmTORSer2448.
Pretreatment of human MCs using the mTORC1 inhibitor rapamycin, the mTORC1/mTORC2
inhibitor Torin1, or the two flavonoids decreases both gene expression and
release (P < 0.0001) of all three mediators. Methoxyluteolin is a more potent
human MC inhibitor than luteolin or Torin1, implicating other MC protein targets
in addition to the mTOR complex. These findings indicate that mTOR is partially
involved in the neuropeptide stimulation of MCs, but the novel flavonoid
methoxyluteolin inhibits the response entirely, suggesting that it may be
developed for treatment of allergic and inflammatory diseases.
PMID- 28404690
TI - Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites.
AB - The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein
that regulates the packaging and subsequent release of dopamine and other
monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a
novel compound that selectively inhibits VMAT2, is approved for the treatment of
tardive dyskinesia. Valbenazine is converted to two significant circulating
metabolites in vivo, namely, (+)-alpha-dihydrotetrabenazine (R,R,R-HTBZ) and a
mono-oxy metabolite, NBI-136110. Radioligand-binding studies were conducted to
assess and compare valbenazine, tetrabenazine, and their respective metabolites
in their abilities to selectively and potently inhibit [3H]-HTBZ binding to VMAT2
in rat striatal, rat forebrain, and human platelet homogenates. A broad panel
screen was conducted to evaluate possible off-target interactions of valbenazine,
R,R,R-HTBZ, and NBI-136110 at >80 receptor, transporter, and ion channel sites.
Radioligand binding showed R,R,R-HTBZ to be a potent VMAT2 inhibitor in
homogenates of rat striatum (Ki = 1.0-2.8 nM), rat forebrain (Ki = 4.2 nM), and
human platelets (Ki = 2.6-3.3 nM). Valbenazine (Ki = 110-190 nM) and NBI-136110
(Ki = 160-220 nM) also exhibited inhibitory effects on VMAT2, but with lower
potency than R,R,R-HTBZ. Neither valbenazine, R,R,R-HTBZ, nor NBI-136110 had
significant off-target interactions at serotonin (5-HT1A, 5-HT2A, 5-HT2B) or
dopamine (D1 or D2) receptor sites. In vivo studies measuring ptosis and
prolactin secretion in the rat confirmed the specific and dose-dependent
interactions of tetrabenazine and R,R,R-HTBZ with VMAT2. Evaluations of potency
and selectivity of tetrabenazine and its pharmacologically active metabolites
were also performed. Overall, the pharmacologic characteristics of valbenazine
appear consistent with the favorable efficacy and tolerability findings of recent
clinical studies [KINECT 2 (NCT01733121), KINECT 3 (NCT02274558)].
PMID- 28404692
TI - Are attending physician rotations costing hospitalized patients their lives?
PMID- 28404691
TI - Exemestane and Its Active Metabolite 17-Hydroexemestane Induce UDP
Glucuronosyltransferase (UGT) 2B17 Expression in Breast Cancer Cells.
AB - Exemestane (EXE) is an aromatase inhibitor indicated for endocrine therapy of
breast cancer in postmenopausal women. The primary active metabolite of EXE, 17
hydroexemestane (17-HE), is inactivated via glucuronidation, mainly by UDP
glucuronosyltransferase 2B17 (UGT2B17). UGT2B17 also has a primary role in
inactivation of endogenous androgens testosterone and dihydrotestosterone and may
play an important role in regulation of breast and prostate tumor intracrinology.
We recently reported that UGT2B17 could be induced by both estrogenic and
androgenic ligands in breast cancer cells via binding of the estrogen receptor
alpha (ERalpha) or the androgen receptor (AR) to a complex regulatory unit in the
proximal UGT2B17 promoter. In this study we show that both EXE and 17-HE increase
UGT2B17 mRNA levels in breast cancer MCF-7 and MDA-MB-453 cells, and increase
glucuronidation of UGT2B17 substrates, including 17-HE and androsterone. Using
antagonists of ERalpha and AR as well as inhibition mediated by small interfering
RNA (siRNA) we demonstrate that EXE and 17-HE induce UGT2B17 expression primarily
via the AR. This result is consistent with previous reports that 17-HE can act as
an AR ligand. In vitro studies suggest that multiple steroid-responsive DNA
elements within the proximal promoter are involved in the response to 17-HE
liganded AR. The up-regulation of UGT2B17 by EXE and 17-HE in breast cancer cells
might enhance the local metabolism of 17-HE as well as that of endogenous
androgens, hence impacting potentially on treatment outcomes.
PMID- 28404694
TI - Canadian list of essential medications: Potential and uncertainties.
PMID- 28404695
TI - Using the Upshur principles to discuss medical fitness to drive.
PMID- 28404696
TI - Scotiabank and CFPC: time for a frank talk.
PMID- 28404697
TI - Response.
PMID- 28404698
TI - Choosing Wisely Canada.
PMID- 28404699
TI - No evidence for benefit of medication for obesity.
PMID- 28404700
TI - Fallacy of yes or no choices.
PMID- 28404701
TI - Diagnosis and management of psoriasis.
AB - OBJECTIVE: To provide primary care clinicians with an up-to-date and practical
overview of the diagnosis and management of psoriasis. QUALITY OF EVIDENCE:
PubMed, MEDLINE, EMBASE, and Cochrane databases were searched for relevant meta
analyses, randomized controlled trials, systematic reviews, and observational
studies about the diagnosis and management of psoriasis. MAIN MESSAGE: Psoriasis
is a chronic, multisystem inflammatory disease with predominantly skin and joint
involvement. Beyond the physical dimensions of disease, psoriasis has an
extensive emotional and psychosocial effect on patients, affecting social
functioning and interpersonal relationships. As a disease of systemic
inflammation, psoriasis is associated with multiple comorbidities, including
cardiovascular disease and malignancy. The diagnosis is primarily clinical and a
skin biopsy is seldom required. Depending on the severity of disease, appropriate
treatment can be initiated. For mild to moderate disease, first-line treatment
involves topical therapies including corticosteroids, vitamin D3 analogues, and
combination products. These topical treatments are efficacious and can be safely
initiated and prescribed by primary care physicians. Patients with more severe
and refractory symptoms might require further evaluation by a dermatologist for
systemic therapy. CONCLUSION: Many patients with psoriasis seek initial
evaluation and treatment from their primary care providers. Recognition of
psoriasis, as well as its associated medical and psychiatric comorbidities, would
facilitate timely diagnosis and appropriate management with effective and safe
topical therapies and other medical and psychological interventions, as needed.
More severe and refractory cases might warrant referral to a dermatologist for
further evaluation and possible systemic therapy.
PMID- 28404702
TI - Corticosteroids for renal scar prevention in children with acute pyelonephritis.
AB - Question Acute pyelonephritis in children is of great concern and I usually refer
these patients to a pediatrician or send them to the emergency department owing
to the risk of renal scarring. Are steroids an acceptable treatment to reduce
risk of scarring? Answer Several agents have been studied in an effort to prevent
renal scar formation following acute pyelonephritis in children. Use of
corticosteroids, in conjunction with standard therapy for acute pyelonephritis,
shows promising findings. However, evidence is very limited and steroids should
not be offered on a regular basis as part of treatment.
PMID- 28404703
TI - Olfactory groove and planum sphenoidale meningioma: Dementia masquerade.
PMID- 28404704
TI - Tuberculosis in Canada.
PMID- 28404706
TI - Spinal manipulative therapy for low back pain.
PMID- 28404707
TI - An efficient tool for the primary care management of menopause.
PMID- 28404709
TI - Lost and found.
PMID- 28404708
TI - Practice simulated office orals as a predictor of Certification examination
performance in family medicine.
AB - OBJECTIVE: To determine if performance on practice simulated office orals (SOOs)
conducted during residency training could predict residents' performance on the
SOO component of the College of Family Physicians of Canada's (CFPC's) final
Certification examination. DESIGN: Prospective cohort study. SETTING: University
of Ottawa in Ontario. PARTICIPANTS: Family medicine residents enrolled in the
University of Ottawa's Family Medicine Residency program between July 1, 2012,
and June 30, 2014, who were eligible to write the CFPC Certification examination
in the spring of 2014 and who had participated in all 4 practice SOO examination
sessions; 23 residents met these criteria. MAIN OUTCOME MEASURES: Scores on
practice SOO sessions during fall 2012, spring 2013, fall 2013, and spring 2014;
and the SOO component score on the spring 2014 administration of the CFPC
Certification examination. RESULTS: Weighted least squares regression analysis
using the 4 practice SOO session scores significantly predicted the final
Certification examination SOO score (P < .05), with an adjusted R2 value of 0.29.
Additional analysis revealed that the mean scores for the cohort generated at
each time point were statistically different from each other (P < .001) and that
the relationship over time could be represented by either a linear relationship
or a quadratic relationship. A generalizability study generated a relative
generalizability coefficient of 0.63. CONCLUSION: Our results confirm the
usefulness of practice SOOs as a progress test and demonstrate the feasibility of
using them to predict final scores on the SOO component of the CFPC's
Certification examination.
PMID- 28404710
TI - Honesty, not forgetting, and our fragile world: Linking ecological action and
clinical encounters.
PMID- 28404711
TI - Teaching outside the clinical setting: Twelve steps to feeling more comfortable
and capable with any invitation to teach, based on the Fundamental Teaching
Activities Framework.
PMID- 28404712
TI - Spending wisely.
PMID- 28404715
TI - Doing well and aiming to do better.
PMID- 28404720
TI - Shared Canadian Curriculum in Family Medicine (SHARC-FM): Creating a national
consensus on relevant and practical training for medical students.
AB - PROBLEM ADDRESSED: In 2006, leaders of undergraduate family medicine education
programs faced a series of increasing curriculum mandates in the context of
limited time and financial resources. Additionally, it became apparent that a
hidden curriculum against family medicine as a career choice was active in
medical schools. OBJECTIVE OF PROGRAM: The Shared Canadian Curriculum in Family
Medicine was developed by the Canadian Undergraduate Family Medicine Education
Directors and supported by the College of Family Physicians of Canada as a
national collaborative project to support medical student training in family
medicine clerkship. Its key objective is to enable education leaders to meet
their educational mandates, while at the same time countering the hidden
curriculum and providing a route to scholarship. PROGRAM DESCRIPTION: The Shared
Canadian Curriculum in Family Medicine is an open-access, shared, national
curriculum (www.sharcfm.ca). It contains 23 core clinical topics (determined
through a modified Delphi process) with demonstrable objectives for each. It also
includes low- and medium-fidelity virtual patient cases, point-of-care learning
resources (clinical cards), and assessment tools, all aligned with the core
topics. French translation of the resources is ongoing. CONCLUSION: The core
topics, objectives, and educational resources have been adopted by medical
schools across Canada, according to their needs. The lessons learned from
mounting this multi-institutional collaborative project will help others develop
their own collaborative curricula.
PMID- 28404721
TI - Family medicine residents' training in, knowledge about, and perceptions of
digital rectal examination.
AB - OBJECTIVE: To evaluate family medicine residents' training in, knowledge about,
and perceptions of digital rectal examination (DRE). DESIGN: Descriptive study,
using an online survey that was available in French and English. SETTING: Quebec.
PARTICIPANTS: A total of 217 residents enrolled in a family medicine program.
MAIN OUTCOME MEASURES: Residents' demographic characteristics; the DRE teaching
they received throughout their medical training; their reasons for omitting DRE;
their recognition of DRE indications (strong vs weak) and application of DRE for
10 anorectal complaints; and their perceptions of the overall quality of the DRE
training they received. RESULTS: Of the 879 residents contacted, 217 (25%)
responded to the survey. Throughout their training, one-third of respondents did
not receive any supervision for or feedback on DRE technique. Seventy-one percent
of respondents expressed their inability to identify the nature of abnormal
examination findings at least once during their training. The most frequently
reported reasons to omit DRE were patient refusal, inadequate setting, and lack
of time. CONCLUSION: Most of the residents in this study had omitted DRE at least
once in their clinical work despite recognizing its importance. There was
discordance between recognition of a complaint requiring DRE and execution of
this technique in a clinical setting. Family medicine education programs and
continuing medical education committees should consider including DRE training.
PMID- 28404722
TI - Evaluation of perceived and actual competency in a family medicine objective
structured clinical examination.
AB - OBJECTIVE: To examine the relationship between objective assessment of
performance and self-rated competence immediately before and after participation
in a required summative family medicine clerkship objective structured clinical
examination (OSCE). DESIGN: Learners rated their competence (on a 7-point Likert
scale) before and after an OSCE along 3 dimensions: general, specific, and
professional competencies relevant to family medicine. SETTING: McGill University
in Montreal, Que. PARTICIPANTS: All 168 third-year clinical clerks completing
their mandatory family medicine rotation in 2010 to 2011 were invited to
participate. MAIN OUTCOME MEASURES: Self-ratings of competence and objective
performance scores were compared, and were examined to determine if OSCEs could
be a "corrective" tool for self-rating perceived competence (ie, if the
experience of undergoing an assessment might assist learners in recalibrating
their understanding of their own performance). RESULTS: A total of 140 (83%) of
the third-year clinical clerks participated. Participating in an OSCE decreased
learners' ratings of perceived competence (pre-OSCE score = 4.9, post-OSCE score
= 4.7; F1,3192 = 4.2; P < .05). Learners' mean self-rated competence for all
categories of behaviour (before and after) showed no relationship to OSCE
performance (r < 0.12 and P > .08 for all), nor did ratings of station-relevant
competence (before and after) (r < 0.19 and P > .09 for all). Ratings of
competence before and after the OSCE were correlated for individual students (r >
0.40 and P < .001 for all). CONCLUSION: After the OSCE, students' self-ratings of
perceived competence had decreased, and these ratings had little relationship to
actual performance, regardless of the specificity of the rated competency.
Discordance between perceived and actual competence is neither novel nor unique
to family medicine. However, this discordance is an important consideration for
the development of competency-based curricula.
PMID- 28404727
TI - When less means more: dehydration improves innate immunity in rattlesnakes.
AB - Immune function can vary based on availability of resources, and most studies of
such influences have focused on the co-investment of energy into immune and other
physiological functions. When energy resources are limited, trade-offs exist,
which can compromise immunity for other functions. As with energy, water
limitation can also alter various physiological processes, yet water has received
little consideration for its possible role in modulating immune functions. We
examined the relationship between immunocompetence and hydration state using the
western diamond-backed rattlesnake (Crotalus atrox). This species is known to
undergo substantial seasonal fluctuations in water availability with extreme
limitations during the hot-dry season. We collected blood samples from free
ranging C. atrox to compare osmolality and innate immune function (lysis,
agglutination and bacterial growth inhibition) during the milder and relatively
moister early spring season, the hot-dry season and the hot-wet season. To
isolate effects of dehydration from other possible seasonal influences, we
complemented this field study with a laboratory study in which we withheld food
and water from individually housed adult C. atrox for up to 16 weeks. We
collected blood samples from each snake as it dehydrated and collected a final
sample after the snake was given water ad libitum at the end of the experiment.
Our results demonstrate that C. atrox experience significant dehydration during
the hot-dry season, and that, in general, innate immune function is highly
correlated with osmolality, whether natural or artificially manipulated.
PMID- 28404725
TI - Evolution of the Stomatal Regulation of Plant Water Content.
PMID- 28404728
TI - Costs of immunity and their role in the range expansion of the house sparrow in
Kenya.
AB - There are at least two reasons to study traits that mediate successful range
expansions. First, dispersers will found new populations and thus impact the
distribution and evolution of species. Second, organisms moving into new areas
will influence the fate of resident communities, directly competing with or
indirectly affecting residents by spreading non-native or spilling-back native
parasites. The success of invaders in new areas is likely mediated by a
counterbalancing of costly traits. In new areas where threats are comparatively
rare, individuals that grow rapidly and breed prolifically should be at an
advantage. High investment in defenses should thus be disfavored. In the present
study, we compared the energetic, nutritional and collateral damage costs of an
inflammatory response among Kenyan house sparrow (Passer domesticus) populations
of different ages, asking whether costs were related to traits of individuals
from three different capture sites. Kenya is among the world's most recent range
expansions for this species, and we recently found that the expression of Toll
like receptors (TLRs), leukocyte receptors that instigate inflammatory responses
when bound to microbial elements, was related to the range expansion across the
country. Here, we found (contrary to our expectations) that energetic and
nutritional costs of inflammation were higher, but damage costs were lower, in
range-edge compared with core birds. Moreover, at the individual level, TLR-4
expression was negatively related to commodity costs (energy and a critical amino
acid) of inflammation. Our data thus suggest that costs of inflammation, perhaps
mediated by TLR expression, might mitigate successful range expansions.
PMID- 28404729
TI - Wings as impellers: honey bees co-opt flight system to induce nest ventilation
and disperse pheromones.
AB - Honey bees (Apis mellifera) are remarkable fliers that regularly carry heavy
loads of nectar and pollen, supported by a flight system - the wings, thorax and
flight muscles - that one might assume is optimized for aerial locomotion.
However, honey bees also use this system to perform other crucial tasks that are
unrelated to flight. When ventilating the nest, bees grip the surface of the comb
or nest entrance and fan their wings to drive airflow through the nest, and a
similar wing-fanning behavior is used to disperse volatile pheromones from the
Nasonov gland. In order to understand how the physical demands of these impeller
like behaviors differ from those of flight, we quantified the flapping kinematics
and compared the frequency, amplitude and stroke plane angle during these non
flight behaviors with values reported for hovering honey bees. We also used a
particle-based flow visualization technique to determine the direction and speed
of airflow generated by a bee performing Nasonov scenting behavior. We found that
ventilatory fanning behavior is kinematically distinct from both flight and
scenting behavior. Both impeller-like behaviors drive flow parallel to the
surface to which the bees are clinging, at typical speeds of just under 1 m s-1
We observed that the wings of fanning and scenting bees frequently contact the
ground during the ventral stroke reversal, which may lead to wing wear. Finally,
we observed that bees performing Nasonov scenting behavior sometimes display
'clap-and-fling' motions, in which the wings contact each other during the dorsal
stroke reversal and fling apart at the start of the downstroke. We conclude that
the wings and flight motor of honey bees comprise a multifunctional system, which
may be subject to competing selective pressures because of its frequent use as
both a propeller and an impeller.
PMID- 28404726
TI - Regulation of Strigolactone Biosynthesis by Gibberellin Signaling.
AB - Strigolactones (SLs) are a class of plant hormones that regulate diverse
physiological processes, including shoot branching and root development. They
also act as rhizosphere signaling molecules to stimulate the germination of root
parasitic weeds and the branching of arbuscular mycorrhizal fungi. Although
various types of cross talk between SLs and other hormones have been reported in
physiological analyses, the cross talk between gibberellin (GA) and SLs is poorly
understood. We screened for chemicals that regulate the level of SLs in rice
(Oryza sativa) and identified GA as, to our knowledge, a novel SL-regulating
molecule. The regulation of SL biosynthesis by GA is dependent on the GA receptor
GID1 and F-box protein GID2. GA treatment also reduced the infection of rice
plants by the parasitic plant witchers weed (Striga hermonthica). These data not
only demonstrate, to our knowledge, the novel plant hormone cross talk between SL
and GA, but also suggest that GA can be used to control parasitic weed
infections.
PMID- 28404730
TI - Not flying blind: a comparative study of photoreceptor function in flying and non
flying cockroaches.
AB - Flying is often associated with superior visual performance, as good vision is
crucial for detection and implementation of rapid visually guided aerial
movements. To understand the evolution of insect visual systems it is therefore
important to compare phylogenetically related species with different investments
in flight capability. Here, we describe and compare morphological and
electrophysiological properties of photoreceptors from the habitually flying
green cockroach Panchlora nivea and the American cockroach Periplaneta americana,
which flies only at high ambient temperatures. In contrast to Periplaneta,
ommatidia in Panchlora were characterized by two-tiered rhabdom, which might
facilitate detection of polarized light while flying in the dark. In patch-clamp
experiments, we assessed the absolute sensitivity to light, elementary and
macroscopic light-activated current and voltage responses, voltage-activated
potassium (Kv) conductances, and information transfer. Both species are
nocturnal, and their photoreceptors were similarly sensitive to light. However, a
number of important differences were found, including the presence in Panchlora
of a prominent transient Kv current and a generally low variability in
photoreceptor properties. The maximal information rate in Panchlora was one-third
higher than in Periplaneta, owing to a substantially higher gain and membrane
corner frequency. The differences in performance could not be completely
explained by dissimilarities in the light-activated or Kv conductances; instead,
we suggest that the superior performance of Panchlora photoreceptors mainly
originates from better synchronization of elementary responses. These findings
raise the issue of whether the evolutionary tuning of photoreceptor properties to
visual demands proceeded differently in Blattodea than in Diptera.
PMID- 28404731
TI - Ploidy-dependent changes in the epigenome of symbiotic cells correlate with
specific patterns of gene expression.
AB - The formation of symbiotic nodule cells in Medicago truncatula is driven by
successive endoreduplication cycles and transcriptional reprogramming in
different temporal waves including the activation of more than 600 cysteine-rich
NCR genes expressed only in nodules. We show here that the transcriptional waves
correlate with growing ploidy levels and have investigated how the epigenome
changes during endoreduplication cycles. Differential DNA methylation was found
in only a small subset of symbiotic nodule-specific genes, including more than
half of the NCR genes, whereas in most genes DNA methylation was unaffected by
the ploidy levels and was independent of the genes' active or repressed state. On
the other hand, expression of nodule-specific genes correlated with ploidy
dependent opening of the chromatin as well as, in a subset of tested genes, with
reduced H3K27me3 levels combined with enhanced H3K9ac levels. Our results suggest
that endoreduplication-dependent epigenetic changes contribute to transcriptional
reprogramming in the differentiation of symbiotic cells.
PMID- 28404733
TI - Pressure dependence of viscosity in supercooled water and a unified approach for
thermodynamic and dynamic anomalies of water.
AB - The anomalous decrease of the viscosity of water with applied pressure has been
known for over a century. It occurs concurrently with major structural changes:
The second coordination shell around a molecule collapses onto the first shell.
Viscosity is thus a macroscopic witness of the progressive breaking of the
tetrahedral hydrogen bond network that makes water so peculiar. At low
temperature, water at ambient pressure becomes more tetrahedral and the effect of
pressure becomes stronger. However, surprisingly, no data are available for the
viscosity of supercooled water under pressure, in which dramatic anomalies are
expected based on interpolation between ambient pressure data for supercooled
water and high pressure data for stable water. Here we report measurements with a
time-of-flight viscometer down to [Formula: see text] and up to [Formula: see
text], revealing a reduction of viscosity by pressure by as much as 42%. Inspired
by a previous attempt [Tanaka H (2000) J Chem Phys 112:799-809], we show that a
remarkably simple extension of a two-state model [Holten V, Sengers JV, Anisimov
MA (2014) J Phys Chem Ref Data 43:043101], initially developed to reproduce
thermodynamic properties, is able to accurately describe dynamic properties
(viscosity, self-diffusion coefficient, and rotational correlation time) as well.
Our results support the idea that water is a mixture of a high density, "fragile"
liquid, and a low density, "strong" liquid, the varying proportion of which
explains the anomalies and fragile-to-strong crossover in water.
PMID- 28404732
TI - Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling.
AB - It is widely accepted that the essential role of TRAF6 in vivo is to generate the
Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein
kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is
not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation,
or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63
Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6
mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1,
IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO)
cells, but not in TRAF6 KO or Pellino1/2 double-KO cells. The reexpression of E3
ligase-inactive TRAF6 mutants partially restored IL-1 signaling in TRAF6 KO
cells, but not in TRAF6/Pellino1/Pellino2 triple-KO cells. Pellino1-generated K63
Ub chains activated the TAK1 complex in vitro with similar efficiently to TRAF6
generated K63-Ub chains. The early phase of TLR signaling and the TLR-dependent
secretion of IL-10 (controlled by IRAKs 1 and 2) was only reduced modestly in
primary macrophages from knockin mice expressing the E3 ligase-inactive
TRAF6[L74H] mutant, but the late-phase production of IL-6, IL-12, and TNFalpha
(controlled only by the pseudokinase IRAK2) was abolished. RANKL-induced
signaling in macrophages and the differentiation of bone marrow to osteoclasts
was similar in TRAF6[L74H] and wild-type cells, explaining why the bone structure
and teeth of the TRAF6[L74H] mice was normal, unlike TRAF6 KO mice. We identify
two essential roles of TRAF6 that are independent of its E3 ligase activity.
PMID- 28404734
TI - Physiology in Perspective: The Importance of Integrative Physiology.
PMID- 28404736
TI - The Link Between Adipose Tissue Renin-Angiotensin-Aldosterone System Signaling
and Obesity-Associated Hypertension.
AB - Obese individuals frequently develop hypertension, which is for an important part
attributable to renin-angiotensin-aldosterone system (RAAS) overactivity. This
review summarizes preclinical and clinical evidence on the involvement of
dysfunctional adipose tissue in RAAS activation and on the renal, central, and
vascular mechanisms linking RAAS components to obesity-associated hypertension.
PMID- 28404737
TI - Reprogramming Interferon Regulatory Factor Signaling in Cardiometabolic Diseases.
AB - Interferon regulatory factors (IRFs) are evolutionarily conserved proteins
expressed not only in immune cells but also in other tissues and organs outside
the immune system. In this review, we discuss mechanisms responsible for IRF
mediated innate immune responses and the function and mechanism of IRFs in
cardiometabolic diseases. We focus on the role of IRFs in innate immunity and
cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.
PMID- 28404738
TI - Microbiotal-Host Interactions and Hypertension.
AB - Hypertension, or elevated blood pressure (BP), has been extensively researched
over decades and clearly demonstrated to be caused due to a combination of host
genetic and environmental factors. Although much research remains to be conducted
to pin-point the precise genetic elements on the host genome that control BP, new
lines of evidence are emerging to indicate that, besides the host genome, the
genomes of all indigenous commensal micro-organisms, collectively referred to as
the microbial metagenome or microbiome, are important, but largely understudied,
determinants of BP. Unlike the rigid host genome, the microbiome or the "second
genome" can be altered by diet or microbiotal transplantation in the host. This
possibility is attractive from the perspective of exploiting the microbiotal
composition for clinical management of inherited hypertension. Thus, focusing on
the limited current literature supporting a role for the microbiome in BP
regulation, this review highlights the need to further explore the role of the co
existence of host and the microbiota as an organized biological unit called the
"holobiont" in the context of BP regulation.
PMID- 28404739
TI - Feeding Your Baby In Utero: How the Uteroplacental Circulation Impacts Pregnancy.
AB - The utero-placental circulation links the maternal and fetal circulations during
pregnancy, ensuring adequate gas and nutrient exchange, and consequently fetal
growth. However, our understanding of this circulatory system remains incomplete.
Here, we discuss how the utero-placental circulation is established, how it
changes dynamically during pregnancy, and how this may impact on pregnancy
success, highlighting how we may address knowledge gaps through advances in
imaging and computational modeling approaches.
PMID- 28404735
TI - Pathophysiology of Aortic Valve Stenosis: Is It Both Fibrocalcific and Sex
Specific?
AB - Our understanding of the fundamental biology and identification of efficacious
therapeutic targets in aortic valve stenosis has lagged far behind the fields of
atherosclerosis and heart failure. In this review, we highlight the most
clinically relevant problems facing men and women with fibrocalcific aortic valve
stenosis, discuss the fundamental biology underlying valve calcification and
fibrosis, and identify key molecular points of intersection with sex hormone
signaling.
PMID- 28404741
TI - Avian blastoderm dormancy arrests cells in G2 and suppresses apoptosis.
AB - In most avian species, the early embryo suspends development when the ambient
temperature is too low; the resultant dormant state is called cold torpor.
However, very little is known about dormant avian embryos at the cellular level.
To investigate the molecular processes that occur in the chicken blastoderm
during cold torpor, we performed transcriptome analysis and investigated cellular
responses in dormant embryos. In embryos stored at low temperature, we observed
up-regulation of genes and proteins related to endoplasmic reticulum stress and
stress-activated protein kinase signaling. In addition, the proportion of early
apoptotic cells rose dramatically during torpor, whereas the proportion of late
apoptotic cells was unchanged. Cell cycle analysis revealed that mitotic arrest
occurred at the G2 phase in a DNA damage-independent manner and that the arrest
was alleviated after incubation at 37 degrees C. Our data suggest that the
dormant avian embryo tolerates cold stress by inducing stress-tolerance pathways,
inhibiting late apoptosis, and triggering cell cycle arrest at the G2 phase.-Ko,
M. H., Hwang, Y. S., Rim, J. S., Han, H. J., Han, J. Y. Avian blastoderm dormancy
arrests cells in G2 and suppresses apoptosis.
PMID- 28404742
TI - Autonomic nervous system activation mediates the increase in whole-body glucose
uptake in response to electroacupuncture.
AB - A single bout of low-frequency electroacupuncture (EA) causing muscle
contractions increases whole-body glucose uptake in insulin-resistant rats. We
explored the underlying mechanism of this finding and whether it can be
translated into clinical settings. Changes in glucose infusion rate (GIR) were
measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low
frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS)
and 21 controls matched for age, weight, and body mass index (experiment 1) and
in rats receiving autonomic receptor blockers (experiment 2). GIR was higher
after EA in controls and women with PCOS. Plasma serotonin levels and
homovanillic acid, markers of vagal activity, decreased in both controls and
patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF)
decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in
controls, suggesting increased sympathetic-driven adipose tissue metabolism.
Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the
increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist
also blocked the response but with slower onset. In conclusion, a single bout of
EA increases whole-body glucose uptake by activation of the sympathetic and
partly the parasympathetic nervous systems, which could have important clinical
implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M.,
Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V.,
Jerlhag, E., Sazonova, A., Behre, C. J., Hojlund, K., Thoren, P., Stener
Victorin, E. Autonomic nervous system activation mediates the increase in whole
body glucose uptake in response to electroacupuncture.
PMID- 28404740
TI - In Vitro Models to Study Human Lung Development, Disease and Homeostasis.
AB - The main function of the lung is to support gas exchange, and defects in lung
development or diseases affecting the structure and function of the lung can have
fatal consequences. Most of what we currently understand about human lung
development and disease has come from animal models. However, animal models are
not always fully able to recapitulate human lung development and disease,
highlighting an area where in vitro models of the human lung can compliment
animal models to further understanding of critical developmental and pathological
mechanisms. This review will discuss current advances in generating in vitro
human lung models using primary human tissue, cell lines, and human pluripotent
stem cell derived lung tissue, and will discuss crucial next steps in the field.
PMID- 28404743
TI - Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme
apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant
induced cell death.
AB - Atherosclerotic plaque destabilization is the major determinant of most acute
coronary events. Smooth muscle cell (SMC) death contributes to plaque
destabilization. Here, we describe a novel antiapoptotic mechanism in vascular
SMCs that involves interaction of nuclear glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major
oxidized DNA repair enzyme. GAPDH down-regulation potentiated H2O2-induced DNA
damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage
and protected SMCs against apoptosis. Ape1 down-regulation reversed the
resistance of GAPDH-overexpressing cells to DNA damage and apoptosis, which
indicated that Ape1 is indispensable for GAPDH-dependent protective effects.
GAPDH bound Ape1 in the SMC nucleus, and blocking (or oxidation) of GAPDH active
site cysteines suppressed GAPDH/Ape1 interaction and potentiated apoptosis. GAPDH
up-regulated Ape1 via a transcription factor homeobox protein Hox-A5-dependent
mechanism. GAPDH levels were reduced in atherosclerotic plaque SMCs, and this
effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated
that nuclear GAPDH/Ape1 interaction preserved Ape1 activity, reduced DNA damage,
and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of
nuclear GAPDH/Ape1 interactions may be a novel therapy to increase
atherosclerotic plaque stability.-Hou, X., Snarski, P., Higashi, Y., Yoshida, T.,
Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of glyceraldehyde-3
phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease
I protect smooth muscle cells against oxidant-induced cell death.
PMID- 28404744
TI - The role of CB1 in intestinal permeability and inflammation.
AB - The endocannabinoid system has previously been shown to play a role in the
permeability and inflammatory response of the human gut. The goal of our study
was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl
glycerol (2-AG) on the permeability and inflammatory response of intestinal
epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal
mucosa was modeled using Caco-2 cells. Human tissue was collected from planned
colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting
their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and
JZL184 (a monoacylglycerol lipase inhibitor). Inflammation and ischemia were
simulated with TNF-alpha and IFN-gamma and oxygen deprivation. Permeability
changes were measured by transepithelial electrical resistance. The role of the
CB1 receptor was explored using CB1-knockdown (CB1Kd) intestinal epithelial
cells. Endocannabinoid levels were measured using liquid chromatography-mass
spectrometry. Cytokine secretion was measured using multiplex and ELISA. URB597
and JZL184 caused a concentration-dependent increase in permeability via CB1 (P <
0.0001) and decreased cytokine production. Basolateral application of JZL184
decreased permeability via CB1 (P < 0.0001). URB597 and JZL184 increased the
enhanced (worsened) permeability caused by inflammation and hypoxia (P < 0.0001
and P < 0.05). CB1Kd cells showed reduced permeability response to inflammation
(P < 0.01) but not hypoxia. 2-AG levels were increased in response to
inflammation and hypoxia in Caco-2 cells. In human mucosal tissue, inflammation
increased the secretion of granulocyte macrophage-colony stimulating factor, IL
12, -13, and -15, which was prevented with ex vivo treatment with URB597 and
JZL184, and was inhibited by a CB1 antagonist. The results of this study show
that endogenous AEA and 2-AG production and CB1 activation play a key modulatory
roles in normal intestinal mucosa permeability and in inflammatory and hypoxic
conditions.-Karwad, M. A., Couch, D. G., Theophilidou, E., Sarmad, S., Barrett,
D. A., Larvin, M., Wright, K. L., Lund, J. N., O'Sullivan, S. E. The role of CB1
in intestinal permeability and inflammation.
PMID- 28404746
TI - Wound-induced Ca2+ wave propagates through a simple release and diffusion
mechanism.
AB - Damage-associated molecular patterns (DAMPs) are critical mediators of
information concerning tissue damage from damaged cells to neighboring healthy
cells. ATP acts as an effective DAMP when released into extracellular space from
damaged cells. Extracellular ATP receptors monitor tissue damage and activate a
Ca2+ wave in the surrounding healthy cells. How the Ca2+ wave propagates through
cells after a wound is unclear. Ca2+ wave activation can occur extracellularly
via external receptors or intracellularly through GAP junctions. Three potential
mechanisms to propagate the Ca2+ wave are source and sink, amplifying wave, and
release and diffusion. Both source and sink and amplifying wave regulate ATP
levels using hydrolysis or secretion, respectively, whereas release and diffusion
relies on dilution. Here we systematically test these hypotheses using a
microfluidics assay to mechanically wound an epithelial monolayer in combination
with direct manipulation of ATP hydrolysis and release. We show that a release
and diffusion model sufficiently explains Ca2+-wave propagation after an
epithelial wound. A release and diffusion model combines the benefits of fast
activation at short length scales with a self-limiting response to prevent
unnecessary inflammatory responses harmful to the organism.
PMID- 28404745
TI - Quantitative high-content imaging identifies novel regulators of Neo1 trafficking
at endosomes.
AB - P4-ATPases are a family of putative phospholipid flippases that regulate lipid
membrane asymmetry, which is important for vesicle formation. Two yeast
flippases, Drs2 and Neo1, have nonredundant functions in the recycling of the
synaptobrevin-like v-SNARE Snc1 from early endosomes. Drs2 activity is needed to
form vesicles and regulate its own trafficking, suggesting that flippase activity
and localization are linked. However, the role of Neo1 in endosomal recycling is
not well characterized. To identify novel regulators of Neo1 trafficking and
activity at endosomes, we first identified mutants with impaired recycling of a
Snc1-based reporter and subsequently used high-content microscopy to classify
these mutants based on the localization of Neo1 or its binding partners, Mon2 and
Dop1. This analysis identified a role for Arl1 in stabilizing the Mon2/Dop1
complex and uncovered a new function for Vps13 in early endosome recycling and
Neo1 localization. We further showed that the cargo-selective sorting nexin Snx3
is required for Neo1 trafficking and identified an Snx3 sorting motif in the Neo1
N-terminus. Of importance, the Snx3-dependent sorting of Neo1 was required for
the correct sorting of another Snx3 cargo protein, suggesting that the
incorporation of Neo1 into recycling tubules may influence their formation.
PMID- 28404747
TI - Aep3p-dependent translation of yeast mitochondrial ATP8.
AB - Translation of mitochondrial gene products in Saccharomyces cerevisiae depends on
mRNA-specific activators that bind to the 5' untranslated regions and promote
translation on mitochondrial ribosomes. Here we find that Aep3p, previously shown
to stabilize the bicistronic ATP8-ATP6 mRNA and facilitate initiation of
translation from unformylated methionine, also activates specifically translation
of ATP8 This is supported by several lines of evidence. Temperature-sensitive
aep3 mutants are selectively blocked in incorporating [35S]methionine into Atp8p
at nonpermissive but not at the permissive temperature. This phenotype is not a
consequence of defective transcription or processing of the pre-mRNA. Neither is
it explained by turnover of Aep3p, as evidenced by the failure of aep3 mutants to
express a recoded ARG8m when this normally nuclear gene is substituted for ATP8
in mitochondrial DNA. Finally, translational of ATP8 mRNA in aep3 mutants is
partially rescued by recoded allotopic ATP8 (nATP8) in a high-expression plasmid
or in a CEN plasmid in the presence of recessive mutations in genes involved in
stability and polyadenylation of RNA.
PMID- 28404748
TI - Components of RNA granules affect their localization and dynamics in neuronal
dendrites.
AB - In neurons, RNA transport is important for local protein synthesis. mRNAs are
transported along dendrites as large RNA granules. The localization and dynamics
of Puralpha and Staufen1 (Stau1), major components of RNA transport granules,
were investigated in cultured hippocampal neurons. Puralpha-positive granules
were localized in both the shafts and spines of dendrites. In contrast, Stau1
positive granules tended to be localized mainly in dendritic shafts. More than
90% of Puralpha-positive granules were positive for Stau1 in immature dendrites,
while only half were positive in mature dendrites. Stau1-negative Puralpha
granules tended to be stationary with fewer anterograde and retrograde movements
than Stau1-positive Puralpha granules. After metabotropic glutamate receptor 5
activation, Stau1-positive granules remained in the dendritic shafts, while
Puralpha granules translocated from the shaft to the spine. The translocation of
Puralpha granules was dependent on myosin Va, an actin-based molecular motor
protein. Collectively our findings suggest the possibility that the loss of Stau1
in Puralpha-positive RNA granules might promote their activity-dependent
translocation into dendritic spines, which could underlie the regulation of
protein synthesis in synapses.
PMID- 28404749
TI - Diffusion of lipids and GPI-anchored proteins in actin-free plasma membrane
vesicles measured by STED-FCS.
AB - Diffusion and interaction dynamics of molecules at the plasma membrane play an
important role in cellular signaling and are suggested to be strongly associated
with the actin cytoskeleton. Here we use superresolution STED microscopy combined
with fluorescence correlation spectroscopy (STED-FCS) to access and compare the
diffusion characteristics of fluorescent lipid analogues and GPI-anchored
proteins (GPI-APs) in the live-cell plasma membrane and in actin cytoskeleton
free, cell-derived giant plasma membrane vesicles (GPMVs). Hindered diffusion of
phospholipids and sphingolipids is abolished in the GPMVs, whereas transient
nanodomain incorporation of ganglioside lipid GM1 is apparent in both the live
cell membrane and GPMVs. For GPI-APs, we detect two molecular pools in living
cells; one pool shows high mobility with transient incorporation into
nanodomains, and the other pool forms immobile clusters, both of which disappear
in GPMVs. Our data underline the crucial role of the actin cortex in maintaining
hindered diffusion modes of many but not all of the membrane molecules and
highlight a powerful experimental approach to decipher specific influences on
molecular plasma membrane dynamics.
PMID- 28404750
TI - Human adenine nucleotide translocases physically and functionally interact with
respirasomes.
AB - Members of the adenine nucleotide translocase (ANT) family exchange ADP for ATP
across the mitochondrial inner membrane, an activity that is essential for
oxidative phosphorylation (OXPHOS). Mutations in or dysregulation of ANTs is
associated with progressive external ophthalmoplegia, cardiomyopathy,
nonsyndromic intellectual disability, apoptosis, and the Warburg effect. Binding
partners of human ANTs have not been systematically identified. The absence of
such information has prevented a detailed molecular understanding of the assorted
ANT-associated diseases, including insight into their disparate phenotypic
manifestations. To fill this void, in this study, we define the interactomes of
two human ANT isoforms. Analogous to its yeast counterpart, human ANTs associate
with heterologous partner proteins, including the respiratory supercomplex (RSC)
and other solute carriers. The evolutionarily conserved ANT-RSC association is
particularly noteworthy because the composition, and thereby organization, of
RSCs in yeast and human is different. Surprisingly, absence of the major ANT
isoform only modestly impairs OXPHOS in HEK293 cells, indicating that the low
levels of other isoforms provide functional redundancy. In contrast,
pharmacological inhibition of OXPHOS expression and function inhibits ANT
dependent ADP/ATP exchange. Thus ANTs and the OXPHOS machinery physically
interact and functionally cooperate to enhance ANT transport capacity and
mitochondrial respiration.
PMID- 28404753
TI - Politics as Usual-Not!
PMID- 28404751
TI - Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive
state by nucleoplasmin/nucleophosmin.
AB - The chromosomal passenger complex (CPC) is a conserved, essential regulator of
cell division. As such, significant anti-cancer drug development efforts have
been focused on targeting it, most notably by inhibiting its AURKB kinase
subunit. The CPC is activated by AURKB-catalyzed autophosphorylation on multiple
subunits, but how this regulates CPC interactions with other mitotic proteins
remains unclear. We investigated the hydrodynamic behavior of the CPC in Xenopus
laevis egg cytosol using sucrose gradient sedimentation and in HeLa cells using
fluorescence correlation spectroscopy. We found that autophosphorylation of the
CPC decreases its sedimentation coefficient in egg cytosol and increases its
diffusion coefficient in live cells, indicating a decrease in mass. Using
immunoprecipitation coupled with mass spectrometry and immunoblots, we discovered
that inactive, unphosphorylated CPC interacts with nucleophosmin/nucleoplasmin
proteins, which are known to oligomerize into pentamers and decamers.
Autophosphorylation of the CPC causes it to dissociate from
nucleophosmin/nucleoplasmin. We propose that nucleophosmin/nucleoplasmin
complexes serve as chaperones that negatively regulate the CPC and/or stabilize
its inactive form, preventing CPC autophosphorylation and recruitment to
chromatin and microtubules in mitosis.
PMID- 28404752
TI - Scaling of cytoskeletal organization with cell size in Drosophila.
AB - Spatially organized macromolecular complexes are essential for cell and tissue
function, but the mechanisms that organize micron-scale structures within cells
are not well understood. Microtubule-based structures such as mitotic spindles
scale with cell size, but less is known about the scaling of actin structures
within cells. Actin-rich denticle precursors cover the ventral surface of the
Drosophila embryo and larva and provide templates for cuticular structures
involved in larval locomotion. Using quantitative imaging and statistical
modeling, we demonstrate that denticle number and spacing scale with cell length
over a wide range of cell sizes in embryos and larvae. Denticle number and
spacing are reduced under space-limited conditions, and both features robustly
scale over a 10-fold increase in cell length during larval growth. We show that
the relationship between cell length and denticle spacing can be recapitulated by
specific mathematical equations in embryos and larvae and that accurate denticle
spacing requires an intact microtubule network and the microtubule minus end
binding protein, Patronin. These results identify a novel mechanism of micro
tubule-dependent actin scaling that maintains precise patterns of actin
organization during tissue growth.
PMID- 28404754
TI - Therapeutic Response of Metastatic Colorectal Cancer Harboring a KRAS Missense
Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab.
AB - Over the past decade, subset analyses of retrospective and prospective clinical
studies have determined that KRAS-mutated metastatic colorectal cancers do not
respond effectively to inhibition of epidermal growth factor receptor (EGFR) with
the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the
past few years, the scope of tested variants in the KRAS oncogene has expanded
significantly, and testing of all RAS family genes has become more widely
available in clinical laboratories. Expert consensus guidelines have recommended
not using EGFR inhibitors in patients with KRAS-mutated tumors. However, with
increasing identification of low-prevalence variants, it is conceivable that some
RAS mutations do not provide equivalent resistance to EGFR inhibition compared
with the most prevalent mutations at codons 12, 13, and 61. This report describes
a case of a patient with metastatic colon cancer harboring the p.A59T variant of
KRAS, with objective radiographic response (36% decrease per RECIST 1.1) and
carcinoembryonic antigen biomarker response to panitumumab therapy given with
FOLFIRI chemotherapy. We propose that A59T represents one potential exception to
the guidelines that KRAS mutant tumors fail to respond to therapy with EGFR
inhibitors, altering the paradigm of using this generalized approach.
PMID- 28404755
TI - NCCN Guidelines Insights: Breast Cancer, Version 1.2017.
AB - These NCCN Guidelines Insights highlight the important updates/changes to the
surgical axillary staging, radiation therapy, and systemic therapy
recommendations for hormone receptor-positive disease in the 1.2017 version of
the NCCN Guidelines for Breast Cancer. This report summarizes these updates and
discusses the rationale behind them. Updates on new drug approvals, not available
at press time, can be found in the most recent version of these guidelines at
NCCN.org.
PMID- 28404756
TI - Infusion-Compatible Antibiotic Formulations for Rapid Administration to Improve
Outcomes in Cancer Outpatients With Severe Sepsis and Septic Shock: The Sepsis
STAT Pack.
AB - Background: Patients with cancer are at high risk for severe sepsis and septic
shock (SS/SSh), and a delay in receiving effective antibiotics is strongly
associated with mortality. Delays are due to logistics of clinic flow and drug
delivery. In an era of increasing antimicrobial resistance, combination therapy
may be superior to monotherapy for patients with SS/SSh. Patients and Methods: At
the Seattle Cancer Care Alliance, we implemented the Sepsis STAT Pack (SSP)
program to simplify timely and effective provision of empiric antibiotics and
other resuscitative care to outpatients with cancer with suspected SS/SSh before
hospitalization. Over a 49-month period from January 1, 2008, through January 31,
2012, a total of 162 outpatients with cancer received the intervention. A
retrospective cohort study was conducted to determine outcomes, including
mortality and adverse events associated with the use of a novel care bundle
designed for compatibility of broad-spectrum antibiotics and other supportive
care administered concurrently via rapid infusion at fixed doses. Results: Of 162
sequential patients with cancer and suspected SS/SSh who received the SSP, 71
(44%) were diagnosed with SS/SSh. Median age was 53 years and 65% were men; 141
(87%) had hematologic malignancies, 77 (48%) were transplant recipients, and 80
(49%) were neutropenic. Median time to completion of antibiotics was 111 minutes
(interquartile range, 60-178 minutes). A total of 71 patients (44%) had
bacteremia and 17% of 93 isolates were multidrug-resistant. Possibly related
nephrotoxicity occurred in 7 patients, and 30-day mortality occured in 6 of 160
patients (4%), including 3 of 71 (4%) with SS/SSh. Risk of developing SSh or
death within 30 days increased 18% (95% CI, 4%-34%) for each hour delay to
completion of antibiotics (P=.01). Conclusions: Rapidly administered combination
antibiotics and supportive care delivered emergently to ambulatory patients with
cancer with suspected SS/SSh was well-tolerated and associated with excellent
short-term survival.
PMID- 28404757
TI - Trends in the Incidence and Outcomes of Hospitalized Cancer Patients With
Clostridium difficile Infection: A Nationwide Analysis.
AB - Background: Patients with cancer have several risk factors for Clostridium
difficile infection (CDI), but the impact of CDI on outcomes in this population
needs elucidation. We analyzed the incidence of CDI and its impact on outcomes in
patients with cancer using the National Hospital Discharge Survey (NHDS) database
from 2001 to 2010. Methods: Diagnosis codes were used to identify patients with
cancer and CDI events. Demographics, diagnoses, length of stay (LOS), and
discharge information were abstracted. Multivariate linear and logistic
regression models with weighted analysis were conducted to study CDI incidence
and CDI-associated outcomes. Analyses were performed using SAS version 9.4.
Results: During the 10-year study period, 20.1 million discharges had a cancer
diagnosis. CDI developed in 1.09% of patients with cancer versus 0.77% of
patients without cancer (adjusted odds ratio [aOR], 1.28; 95% CI, 1.28-1.29;
P<.001). The incidence of CDI in patients with cancer increased during the 10
year study period (64.7 per 10,000 discharges in 2001-2002 to 109.1 in 2009-2010;
P<.001). In multivariable analysis, compared with patients with cancer without
CDI, patients with cancer and CDI had a longer mean LOS (5.67 days; 95% CI, 5.39
5.94) and higher rates of in-hospital mortality (aOR, 1.18; 95% CI, 1.16-1.20)
and discharge to a care facility (aOR, 1.74; 95% CI, 1.72-1.75; all P<.001).
Conclusions: In this national database, CDI incidence increased significantly in
patients with cancer over the study period and was associated with prolonged
hospitalization, increased mortality, and discharge to a care facility. Despite
increased attention, CDI remained a serious infection and merits appropriate
prevention and management.
PMID- 28404759
TI - Paving the Way for Dose Banding of Chemotherapy: An Analytical Approach.
AB - Background: In an interdepartmental cooperation, we investigated the feasibility
and benefits of implementing dose banding of chemotherapy at our medical center.
Based on this concept, chemotherapy doses are clustered into bands of similar
dosage levels, thereby allowing the preproduction of frequently used standard
doses of drugs, with sufficient physicochemical stability. Although established
practice in the United Kingdom, there is little published evidence of its
introduction elsewhere. Methods: We performed an analysis of local prescribing
practice (22,310 chemotherapies) and identified gemcitabine, 5-fluorouracil, and
carboplatin, among various others, as cytotoxic drugs suitable for dose banding.
Results: First, we determined the physicochemical stability of the selected
chemotherapy drugs during 12-weeks' storage by performing pH analysis and visual
examination for color change or particles. No relevant changes were identified.
Gemcitabine was selected for quantitative high-performance liquid chromatography
analysis and we were able to show that >=95% remained after 12 weeks' storage, in
accordance with international guidelines. To simulate a worst case scenario, we
performed microbiological stability testing of simulated cytotoxic compounding by
replacing the cytotoxic drug with liquid media. Samples were incubated over
defined storage time points (3, 6, and 12 weeks) and evaluated using the direct
inoculation method. For the container integrity test, we deposited the samples
into highly contaminated broth for 1 hour. Microbiological stability was
demonstrated in both tests for the full storage period. Conclusions: Our data
show that 12-weeks' storage of selected cytotoxic products is feasible from a
microbiological perspective. Sterility of prepared products was maintained under
extreme storage conditions. Gemcitabine content was in accordance with
international guidelines after 12-weeks' storage. These results support the
introduction of dose-banded gemcitabine products with the predicted advantages of
optimized pharmacy workflow and reduced patient waiting times. We highlight the
need for further research and consensus on the performance of purity analyses in
dose-banded drug products.
PMID- 28404758
TI - Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma.
AB - Background: Regional radiation therapy (RT) has been shown to reduce the risk of
regional recurrence with node-positive cutaneous melanoma. However, risk factors
for regional recurrence, especially in the era of sentinel lymph node biopsy
(SLNB), are less clear. Our goals were to identify risk factors associated with
regional recurrence and to determine whether a radiosensitivity index (RSI) gene
expression signature (GES) could identify patients who experience a survival
benefit with regional RT. Methods: A single-institution, Institutional Review
Board-approved study was performed including 410 patients treated with either
SLNB with or without completion lymph node dissection (LND; n=270) or therapeutic
LND (n=91). Postoperative regional RT was delivered to the involved nodal basin
in 83 cases (20.2%), to a median dose of 54 Gy (range, 30-60 Gy) in 27 fractions
(range, 5-30). Primary outcomes were regional control and overall survival by RSI
GES status. Results: Median follow-up was 69 months (range, 13-180).
Postoperative regional RT was associated with a reduced risk of regional
recurrence among all patients on univariate (5-year estimate: 95.0% vs 83.3%;
P=.036) and multivariate analysis (hazard ratio[HR], 0.15; 95% CI, 0.05-0.43;
P<.001). Among higher-risk subgroups, regional RT was associated with a lower
risk of regional recurrence among patients with clinically detected lymph nodes
(n=175; 5-year regional control: 94.1% vs 69.5%; P=.003) and extracapsular
extension (ECE) present (n=138; 5-year regional control: 96.7% vs 62.2%; P<.001).
Among a subset of radiated patients with gene expression data available, a low
RSI GES (radiosensitive) tumor status was associated with improved survival
compared with a high RSI GES (5-year: 75% vs 0%; HR, 10.68; 95% CI, 1.24-92.14).
Conclusions: Regional RT was associated with a reduced risk of regional
recurrence among patients with ECE and clinically detected nodal disease. Gene
expression data show promise for better predicting radiocurable patients in the
future. In the era of increasingly effective systemic therapies, the value of
improved regional control potentially takes on greater significance.
PMID- 28404760
TI - The 21-Gene Recurrence Score Assay for Node-Positive, Early-Stage Breast Cancer
and Impact of RxPONDER Trial on Chemotherapy Decision-Making: Have Clinicians
Already Decided?
AB - Background: The 21-gene recurrence score (RS) assay is retrospectively validated
for assessing prognosis and benefit from chemotherapy in hormone receptor
positive, early-stage breast cancer (EBC) with low RS. We hypothesized that
oncologists have already incorporated the RS assay for decision-making in higher
risk, node-positive disease, despite the lack of prospective data and contrary to
NCCN Guideline recommendations. This study provides the first analysis of trends
and differences in RS use and therapeutic implications in a population-based data
set of patients with node-positive EBC. It also assesses the impact of the
RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node
positive EBC cases diagnosed during 2010 through 2012 and included in the
National Cancer Data Base were used. Multivariate logistic regression was used to
estimate test use and impact on chemotherapy recommendations. Results: The RS
assay was ordered for 16.5% of the 80,405 identified patients. Of all variables,
the RS assay had the strongest association with chemotherapy recommendation, with
adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy
recommendation were significantly lower for the group who received the test (AOR,
0.21; 95% CI, 0.20-0.22). When divided based on the cutoff point of 25 adopted by
the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of
chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR,
0.32; 95% CI, 0.26-0.40). Test use was lower for blacks, community centers,
uninsured/governmentally insured patients, higher tumor grade, larger tumor size,
and more nodes involved. Chemotherapy recommendation was higher for patients of
younger age, with private insurance, and with higher tumor grade, size, and
number of nodes involved. Black patients had significantly higher RS (AOR, 1.37;
95% CI, 1.25-1.79). Conclusions: The RS assay influences clinicians' chemotherapy
recommendation in node-positive EBC. Clinicians are using the inclusion criteria
of the RxPONDER trial before its final release. Black patients have higher RS,
likely representing worse biology. Significant differences exist in test use and
clinical implications based on race, insurance, and facility.
PMID- 28404761
TI - Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in
Oncology.
AB - This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC)
focuses on targeted therapies and immunotherapies for metastatic NSCLC, because
therapeutic recommendations are rapidly changing for metastatic disease. For
example, new recommendations were added for atezolizumab, ceritinib, osimertinib,
and pembrolizumab for the 2017 updates.
PMID- 28404762
TI - Implementation of Systemic Hedgehog Inhibitors in Daily Practice as Neoadjuvant
Therapy.
AB - The most common cancer in both men and women is basal cell carcinoma (BCC).
Although most primary and recurrent BCCs have high cure rates with standard
therapies, advanced BCCs present a greater treatment challenge, especially in
cosmetically and functionally sensitive areas. In patients unable to undergo
surgery or radiation therapy, hedgehog inhibitors can be used neoadjuvantly to
reduce tumor size, decreasing the extent and complexity of any subsequent surgery
and providing either a cure or palliation. The goal of this review is to
summarize the pharmacology, efficacy, and safety of systemic hedgehog inhibitors,
as well as their role in daily practice as neoadjuvant therapy. Relevant English
language literature was identified and evaluated based on results from database
searches of PubMed. Terms searched included, but were not limited to,
"vismodegib," "Erivedge," "sonidegib," "DE225," "BCC," and "neoadjuvant
treatment." Additional literature was identified from the reference lists of
previously identified articles. The authors' personal experience in treating
advanced BCC using hedgehog inhibitors has been incorporated into the
recommendations made herein.
PMID- 28404763
TI - Why a One Size Fits All Approach to RAS Might Not Fit Colorectal Cancer.
PMID- 28404765
TI - NCCN News.
PMID- 28404766
TI - Randomised controlled trial of a sexual risk reduction intervention for STI
prevention among men who have sex with men in the USA.
AB - OBJECTIVES: Novel interventions to address sexual risk taking and slow rates of
STIs are urgently needed, in particular among black men who have sex with men
(MSM) in the USA. Serosorting, or limiting condomless sex acts to partners of the
same HIV status, is commonly practised among MSM, yet can lead to STI and remains
largely unaddressed by public health agencies. METHODS: A two-arm, randomised
controlled trial was conducted from 2012 to 2015. This trial assessed the effects
of a single-session, sexual partner selection and risk decision intervention
(experimental arm) versus a single-session, Centers for Disease Control and
Prevention-based, sexual risk reduction intervention (control arm) on
psychosocial measures, sexual risk taking and STI. RESULTS: At study follow-ups,
multiple beneficial changes were observed on sexual risk beliefs measures (ie,
changes in serosorting and condom use beliefs, and HIV risk perceptions) and
sexual risk taking among the experimental arm relative to the control arm.
Overall main effects, however, of the intervention on STI outcomes on year-long
follow-ups were non-significant. There was evidence for short-term effects on STI
outcomes, and self-report of multiple STIs and STI symptoms demonstrated positive
effects over the follow-up period. CONCLUSIONS: Brief interventions to address
sexual risk taking can result in short-term beneficial outcomes and can be
incorporated into currently existing infrastructure at healthcare agencies.
Additional intervention will be necessary for demonstrating long-term results.
TRIAL REGISTRATION NUMBER: NCT02128594.
PMID- 28404767
TI - A Conversation with Joan Brugge.
PMID- 28404768
TI - DJ-1 overexpression restores ischaemic post-conditioning-mediated
cardioprotection in diabetic rats: role of autophagy.
AB - IPO (ischaemic post-conditioning) is a promising method of alleviating myocardial
IR (ischaemia-reperfusion) injury; however, IPO-mediated cardioprotection is lost
in diabetic hearts via mechanisms that remain largely unclear. We hypothesized
that decreased cardiac expression of DJ-1, a positive modulator of autophagy,
compromises the effectiveness of IPO-induced cardioprotection in diabetic rats.
Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion
followed by 120 min of reperfusion) exhibited more severe myocardial injury, less
cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monophosphate
activated protein kinase)/mTOR (mammalian target of rapamycin) pathway activity
than non-diabetic rats. IPO significantly attenuated myocardial injury and up
regulated cardiac DJ-1 expression, AMPK/mTOR activity and autophagy in non
diabetic rats but not in diabetic rats. AAV9 (adeno-associated virus 9)-mediated
cardiac DJ-1 overexpression as well as pretreatment with the autophagy inducer
rapamycin restored IPO-induced cardioprotection in diabetic rats, an effect
accompanied by AMPK/mTOR activation and autophagy up-regulation. Combining HPO
(hypoxic post-conditioning) with DJ-1 overexpression markedly attenuated HR
(hypoxia-reoxygenation) injury in H9c2 cells with high glucose (HG, 30 mM)
exposure, accompanied by AMPK/mTOR signalling activation and autophagy up
regulation. The DJ-1 overexpression-mediated preservation of HPO-induced
cardioprotection was completely inhibited by the AMPK inhibitor compound C (CC)
and the autophagy inhibitor 3-MA (3-methyladenine). Thus, decreased cardiac DJ-1
expression, which results in impaired AMPK/mTOR signalling and decreased
autophagy, could be a major mechanism underlying the loss of IPO-induced
cardioprotection in diabetes.
PMID- 28404770
TI - Endovascular retrieval of dental needle retained in the internal carotid artery.
AB - Intravascular foreign bodies are a known complication of medical and dental
procedures. Dental anesthetic needles may be broken off and retained in the
oropharynx. These needles have occasionally been reported to migrate through the
oral mucosa in to deeper structures. Here we present the case of a 57-year-old
man who had a retained dental needle that had migrated into his internal carotid
artery. The needle was removed using endovascular techniques. To our knowledge,
this is the first report of a retained dental needle being retrieved using this
method. We review the literature on intravascular foreign bodies, retained dental
needles, and endovascular techniques for retrieval of such foreign bodies.
PMID- 28404769
TI - A decrease in blood pressure is associated with unfavorable outcome in patients
undergoing thrombectomy under general anesthesia.
AB - BACKGROUND: Up to two-thirds of patients are either dependent or dead 3 months
after thrombectomy for acute ischemic stroke (AIS). Loss of cerebral
autoregulation may render patients with AIS vulnerable to decreases in mean
arterial pressure (MAP). OBJECTIVE: To determine whether a fall in MAP during
intervention under general anesthesia (GA) affects functional outcome. METHODS:
This subgroup analysis included patients from the MR CLEAN trial treated with
thrombectomy under GA. The investigated variables were the difference between MAP
at baseline and average MAP during GA (DeltaMAP) as well as the difference
between baseline MAP and the lowest MAP during GA (DeltaLMAP). Their association
with a shift towards better outcome on the modified Rankin Scale (mRS) after 90
days was determined using ordinal logistic regression with adjustment for
prognostic baseline variables. RESULTS: Sixty of the 85 patients treated under GA
in MR CLEAN had sufficient anesthetic information available for the analysis. A
greater DeltaMAP was associated with worse outcome (adjusted common OR (acOR)
0.95 per point mm Hg, 95% CI 0.92 to 0.99). An average MAP during GA 10 mm Hg
lower than baseline MAP constituted a 1.67 times lower odds of a shift towards
good outcome on the mRS. For DeltaLMAP this association was not significant (acOR
0.97 per mm Hg, 95% CI 0.94 to 1.00, p=0.09). CONCLUSIONS: A decrease in MAP
during intervention under GA compared with baseline is associated with worse
outcome. TRIAL REGISTRATION NUMBER: NTR1804; ISRCTN10888758; post-results.
PMID- 28404771
TI - Social foraging and individual consistency in following behaviour: testing the
information centre hypothesis in free-ranging vultures.
AB - Uncertainties regarding food location and quality are among the greatest
challenges faced by foragers and communal roosting may facilitate success through
social foraging. The information centre hypothesis (ICH) suggests that uninformed
individuals at shared roosts benefit from following informed individuals to
previously visited resources. We tested several key prerequisites of the ICH in a
social obligate scavenger, the Eurasian griffon vulture (Gyps fulvus), by
tracking movements and behaviour of sympatric individuals over extended periods
and across relatively large spatial scales, thereby precluding alternative
explanations such as local enhancement. In agreement with the ICH, we found that
'informed' individuals returning to previously visited carcasses were followed by
'uninformed' vultures that consequently got access to these resources. When a
dyad (two individuals that depart from the same roost within 2 min of each other)
included an informed individual, they spent a higher proportion of the flight
time close to each other at a shorter distance between them than otherwise.
Although all individuals occasionally profited from following others, they
differed in their tendencies to be informed or uninformed. This study provides
evidence for 'following behaviour' in natural conditions and demonstrates
differential roles and information states among foragers within a population.
Moreover, demonstrating the possible reliance of vultures on following behaviour
emphasizes that individuals in declining populations may suffer from reduced
foraging efficiency.
PMID- 28404772
TI - Known mutator alleles do not markedly increase mutation rate in clinical
Saccharomyces cerevisiae strains.
AB - Natural selection has the potential to act on all phenotypes, including genomic
mutation rate. Classic evolutionary theory predicts that in asexual populations,
mutator alleles, which cause high mutation rates, can fix due to linkage with
beneficial mutations. This phenomenon has been demonstrated experimentally and
may explain the frequency of mutators found in bacterial pathogens. By contrast,
in sexual populations, recombination decouples mutator alleles from beneficial
mutations, preventing mutator fixation. In the facultatively sexual yeast
Saccharomyces cerevisiae, segregating alleles of MLH1 and PMS1 have been shown to
be incompatible, causing a high mutation rate when combined. These alleles had
never been found together naturally, but were recently discovered in a cluster of
clinical isolates. Here we report that the incompatible mutator allele
combination only marginally elevates mutation rate in these clinical strains.
Genomic and phylogenetic analyses provide no evidence of a historically elevated
mutation rate. We conclude that the effect of the mutator alleles is dampened by
background genetic modifiers. Thus, the relationship between mutation rate and
microbial pathogenicity may be more complex than once thought. Our findings
provide rare observational evidence that supports evolutionary theory suggesting
that sexual organisms are unlikely to harbour alleles that increase their genomic
mutation rate.
PMID- 28404773
TI - Not equal in the face of habitat change: closely related fishes differ in their
ability to use predation-related information in degraded coral.
AB - Coral reefs are biodiversity hotpots that are under significant threat due to the
degradation and death of hard corals. When obligate coral-dwelling species die,
the remaining species must either move or adjust to the altered conditions. Our
goal was to investigate the effect of coral degradation on the ability of coral
reef fishes to assess their risk of predation using alarm cues from injured
conspecifics. Here, we tested the ability of six closely related species of
juvenile damselfish (Pomacentridae) to respond to risk cues in both live coral or
dead-degraded coral environments. Of those six species, two are exclusively
associated with live coral habitats, two are found mostly on dead-degraded coral
rubble, while the last two are found in both habitat types. We found that the two
live coral associates failed to respond appropriately to the cues in water from
degraded habitats. In contrast, the cue response of the two rubble associates was
unaffected in the same degraded habitat. Interestingly, we observed a mixed
response from the species found in both habitat types, with one species
displaying an appropriate cue response while the other did not. Our second
experiment suggested that the lack of responses stemmed from deactivation of the
alarm cues, rather than the inability of the species to smell. Habitat preference
(live coral versus dead coral associates) and phylogeny are good candidates for
future work aimed at predicting which species are affected by coral degradation.
Our results point towards a surprising level of variation in the ability of
congeneric species to fare in altered habitats and hence underscores the
difficulty of predicting community change in degraded habitats.
PMID- 28404774
TI - Changes in the location of biodiversity-ecosystem function hot spots across the
seafloor landscape with increasing sediment nutrient loading.
AB - Declining biodiversity and loss of ecosystem function threatens the ability of
habitats to contribute ecosystem services. However, the form of the relationship
between biodiversity and ecosystem function (BEF) and how relationships change
with environmental change is poorly understood. This limits our ability to
predict the consequences of biodiversity loss on ecosystem function, particularly
in real-world marine ecosystems that are species rich, and where multiple
ecosystem functions are represented by multiple indicators. We investigated
spatial variation in BEF relationships across a 300 000 m2 intertidal sandflat by
nesting experimental manipulations of sediment pore water nitrogen concentration
into sites with contrasting macrobenthic community composition. Our results
highlight the significance of many different elements of biodiversity associated
with environmental characteristics, community structure, functional diversity,
ecological traits or particular species (ecosystem engineers) to important
functions of coastal marine sediments (benthic oxygen consumption, ammonium pore
water concentrations and flux across the sediment-water interface). Using the BEF
relationships developed from our experiment, we demonstrate patchiness across a
landscape in functional performance and the potential for changes in the location
of functional hot and cold spots with increasing nutrient loading that have
important implications for mapping and predicating change in functionality and
the concomitant delivery of ecosystem services.
PMID- 28404775
TI - Stable producer-scrounger dynamics in wild birds: sociability and learning speed
covary with scrounging behaviour.
AB - There has been extensive game-theoretic modelling of conditions leading to
equilibria of producer-scrounger dichotomies in groups. However there is a
surprising paucity of experimental evidence in wild populations. Here, we examine
producer-scrounger games in five subpopulations of birds feeding at a socially
learnt foraging task. Over four weeks, a bimodal distribution of producers and
scroungers emerged in all areas, with pronounced and consistent individual tactic
specialization persisting over 3 years. Tactics were unrelated to exploratory
personality, but correlated with latency to contact and learn the foraging task,
with the late arrivers and slower learners more likely to adopt the scrounging
role. Additionally, the social environment was also important: at the broad
scale, larger subpopulations with a higher social density contained
proportionally more scroungers, while within subpopulations scroungers tended to
be central in the social network and be observed in larger foraging flocks. This
study thus provides a rare example of a stable, dimorphic distribution of
producer-scrounger tactics in a wild population. It further gives support across
multiple scales for a major prediction of social foraging theory; that the
frequency of scroungers increases with group size.
PMID- 28404776
TI - Dry habitats were crucibles of domestication in the evolution of agriculture in
ants.
AB - The evolution of ant agriculture, as practised by the fungus-farming 'attine'
ants, is thought to have arisen in the wet rainforests of South America about 55
65 Ma. Most subsequent attine agricultural evolution, including the domestication
event that produced the ancestor of higher attine cultivars, is likewise
hypothesized to have occurred in South American rainforests. The 'out-of-the
rainforest' hypothesis, while generally accepted, has never been tested in a
phylogenetic context. It also presents a problem for explaining how fungal
domestication might have occurred, given that isolation from free-living
populations is required. Here, we use phylogenomic data from ultra-conserved
element (UCE) loci to reconstruct the evolutionary history of fungus-farming
ants, reduce topological uncertainty, and identify the closest non-fungus-growing
ant relative. Using the phylogeny we infer the history of attine agricultural
systems, habitat preference and biogeography. Our results show that the out-of
the-rainforest hypothesis is correct with regard to the origin of attine ant
agriculture; however, contrary to expectation, we find that the transition from
lower to higher agriculture is very likely to have occurred in a seasonally dry
habitat, inhospitable to the growth of free-living populations of attine fungal
cultivars. We suggest that dry habitats favoured the isolation of attine
cultivars over the evolutionary time spans necessary for domestication to occur.
PMID- 28404778
TI - Correction to 'Adiposity, compared to masculinity, serves as a more valid cue to
immunocompetence in human mate choice'.
PMID- 28404777
TI - Transcriptomics of an extended phenotype: parasite manipulation of wasp social
behaviour shifts expression of caste-related genes.
AB - Parasites can manipulate host behaviour to increase their own transmission and
fitness, but the genomic mechanisms by which parasites manipulate hosts are not
well understood. We investigated the relationship between the social paper wasp,
Polistes dominula, and its parasite, Xenos vesparum (Insecta: Strepsiptera), to
understand the effects of an obligate endoparasitoid on its host's brain
transcriptome. Previous research suggests that X. vesparum shifts aspects of host
social caste-related behaviour and physiology in ways that benefit the
parasitoid. We hypothesized that X. vesparum-infested (stylopized) females would
show a shift in caste-related brain gene expression. Specifically, we predicted
that stylopized females, who would normally be workers, would show gene
expression patterns resembling pre-overwintering queens (gynes), reflecting gyne
like changes in behaviour. We used RNA-sequencing data to characterize patterns
of brain gene expression in stylopized females and compared these with those of
unstylopized workers and gynes. In support of our hypothesis, we found that
stylopized females, despite sharing numerous physiological and life-history
characteristics with members of the worker caste, show gyne-shifted brain
expression patterns. These data suggest that the parasitoid affects its host by
exploiting phenotypic plasticity related to social caste, thus shifting naturally
occurring social behaviour in a way that is beneficial to the parasitoid.
PMID- 28404780
TI - Environmental modification via a quorum sensing molecule influences the social
landscape of siderophore production.
AB - Bacteria produce a wide variety of exoproducts that favourably modify their
environment and increase their fitness. These are often termed 'public goods'
because they are costly for individuals to produce and can be exploited by non
producers (cheats). The outcome of conflict over public goods is dependent upon
the prevailing environment and the phenotype of the individuals in competition.
Many bacterial species use quorum sensing (QS) signalling molecules to regulate
the production of public goods. QS, therefore, determines the cooperative
phenotype of individuals, and influences conflict over public goods. In addition
to their regulatory functions, many QS molecules have additional properties that
directly modify the prevailing environment. This leads to the possibility that QS
molecules could influence conflict over public goods indirectly through non
signalling effects, and the impact of this on social competition has not
previously been explored. The Pseudomonas aeruginosa QS signal molecule PQS is a
powerful chelator of iron which can cause an iron starvation response. Here, we
show that PQS stimulates a concentration-dependent increase in the cooperative
production of iron scavenging siderophores, resulting in an increase in the
relative fitness of non-producing siderophore cheats. This is likely due to an
increased cost of siderophore output by producing cells and a concurrent increase
in the shared benefits, which accrue to both producers and cheats. Although PQS
can be a beneficial signalling molecule for P. aeruginosa, our data suggest that
it can also render a siderophore-producing population vulnerable to competition
from cheating strains. More generally, our results indicate that the production
of one social trait can indirectly affect the costs and benefits of another
social trait.
PMID- 28404779
TI - Open data and digital morphology.
AB - Over the past two decades, the development of methods for visualizing and
analysing specimens digitally, in three and even four dimensions, has transformed
the study of living and fossil organisms. However, the initial promise that the
widespread application of such methods would facilitate access to the underlying
digital data has not been fully achieved. The underlying datasets for many
published studies are not readily or freely available, introducing a barrier to
verification and reproducibility, and the reuse of data. There is no current
agreement or policy on the amount and type of data that should be made available
alongside studies that use, and in some cases are wholly reliant on, digital
morphology. Here, we propose a set of recommendations for minimum standards and
additional best practice for three-dimensional digital data publication, and
review the issues around data storage, management and accessibility.
PMID- 28404781
TI - Climatic niche evolution is faster in sympatric than allopatric lineages of the
butterfly genus Pyrgus.
AB - Understanding how speciation relates to ecological divergence has long fascinated
biologists. It is assumed that ecological divergence is essential to sympatric
speciation, as a mechanism to avoid competition and eventually lead to
reproductive isolation, while divergence in allopatry is not necessarily
associated with niche differentiation. The impact of the spatial context of
divergence on the evolutionary rates of abiotic dimensions of the ecological
niche has rarely been explored for an entire clade. Here, we compare the
magnitude of climatic niche shifts between sympatric versus allopatric divergence
of lineages in butterflies. By combining next-generation sequencing, parametric
biogeography and ecological niche analyses applied to a genus-wide phylogeny of
Palaearctic Pyrgus butterflies, we compare evolutionary rates along eight
climatic dimensions across sister lineages that diverged in large-scale sympatry
versus allopatry. In order to examine the possible effects of the spatial scale
at which sympatry is defined, we considered three sets of biogeographic
assignments, ranging from narrow to broad definition. Our findings suggest higher
rates of niche evolution along all climatic dimensions for sister lineages that
diverge in sympatry, when using a narrow delineation of biogeographic areas. This
result contrasts with significantly lower rates of climatic niche evolution found
in cases of allopatric speciation, despite the biogeographic regions defined here
being characterized by significantly different climates. Higher rates in
allopatry are retrieved when biogeographic areas are too widely defined-in such a
case allopatric events may be recorded as sympatric. Our results reveal the macro
evolutionary significance of abiotic niche differentiation involved in speciation
processes within biogeographic regions, and illustrate the importance of the
spatial scale chosen to define areas when applying parametric biogeographic
analyses.
PMID- 28404782
TI - Signatures of optimal control in pairs of schooling zebrafish.
AB - Animals moving in groups coordinate their motion to remain cohesive. A large
amount of data and analysis of movement coordination has been obtained in several
species, but we are lacking theoretical frameworks that can derive the form of
coordination rules. Here, we examine whether optimal control theory can predict
the rules underlying social interactions from first principles. We find that a
control rule which is designed to minimize the time it would take a pair of
schooling fish to form a cohesively moving unit correctly predicts the
characteristics of social interactions in fish. Our methodology explains why
social attraction is negatively modulated by self-motion velocity and positively
modulated by partner motion velocity, and how the biomechanics of fish swimming
can shape the form of social forces. Crucially, the values of all parameters in
our model can be estimated from independent experiments that need not relate to
measurement of social interactions. We test our theory by showing a good match
with experimentally observed social interaction rules in zebrafish. In addition
to providing a theoretical rationale for observed decision rules, we suggest that
this framework opens new questions about tuning problems and learnability of
collective behaviours.
PMID- 28404783
TI - A faster escape does not enhance survival in zebrafish larvae.
AB - An escape response is a rapid manoeuvre used by prey to evade predators.
Performing this manoeuvre at greater speed, in a favourable direction, or from a
longer distance have been hypothesized to enhance the survival of prey, but these
ideas are difficult to test experimentally. We examined how prey survival depends
on escape kinematics through a novel combination of experimentation and
mathematical modelling. This approach focused on zebrafish (Danio rerio) larvae
under predation by adults and juveniles of the same species. High-speed three
dimensional kinematics were used to track the body position of prey and predator
and to determine the probability of behavioural actions by both fish. These
measurements provided the basis for an agent-based probabilistic model that
simulated the trajectories of the animals. Predictions of survivorship by this
model were found by Monte Carlo simulations to agree with our observations and we
examined how these predictions varied by changing individual model parameters.
Contrary to expectation, we found that survival may not be improved by increasing
the speed or altering the direction of the escape. Rather, zebrafish larvae
operate with sufficiently high locomotor performance due to the relatively slow
approach and limited range of suction feeding by fish predators. We did find that
survival was enhanced when prey responded from a greater distance. This is an
ability that depends on the capacity of the visual and lateral line systems to
detect a looming threat. Therefore, performance in sensing, and not locomotion,
is decisive for improving the survival of larval fish prey. These results offer a
framework for understanding the evolution of predator-prey strategy that may
inform prey survival in a broad diversity of animals.
PMID- 28404784
TI - Correction to 'Early life inflammation, immune response and ageing'.
PMID- 28404785
TI - Moving past the problematisation of tobacco farming: insights from South India.
AB - INTRODUCTION: Tobacco control actors increasingly recognise the importance of
supply-side issues in seeking to address the problem of global tobacco
consumption. However, research in this field often depicts tobacco production as
a problem for farmers and as a malaise of the global industry. This paper the
case of chewing tobacco producers in South India to explore why tobacco remains
so resilient in this region. METHODS: Semi-structured interviews with 68 tobacco
farmers and traders in 38 villages across five districts of Tamil Nadu,
triangulated with informal discussions with over 100 agrarian actors both
connected and unconnected to tobacco, extensive ethnographic field notes, and
interviews with state and NGO actors. Representative sampling was not possible
due to a lack of data on what constituted the 'population'. Therefore interviews
were based on snowballing methods, with the aim being to capture the general
scenario across five districts where tobacco is produced. RESULTS: The case
highlighted the lack of a clear 'industry' which was exploiting farmers. Instead,
tobacco was favoured by producers due to its drought resistance in a region of
water scarcity, and it offered high levels of remuneration in certain
circumstances where farmers are able to cure the leaf. It also afforded increased
bargaining power to farmers in relation to traders as it is able to be stored and
sold in low seasons by some. Finally, where exploitation of farmers by traders
was evident, this was not necessarily unique to tobacco. DISCUSSION: The paper
ultimately advocates further research on locally specific settings to better
understand why tobacco cash crop remains so resilient in the Global South today,
and a move beyond problematisations of the tobacco industry alone when looking at
production.
PMID- 28404786
TI - Causes and consequences of nuclear gene positioning.
AB - The eukaryotic genome is organized in a manner that allows folding of the genetic
material in the confined space of the cell nucleus, while at the same time
enabling its physiological function. A major principle of spatial genome
organization is the non-random position of genomic loci relative to other loci
and to nuclear bodies. The mechanisms that determine the spatial position of a
locus, and how position affects function, are just beginning to be characterized.
Initial results suggest that there are multiple, gene-specific mechanisms and the
involvement of a wide range of cellular machineries. In this Commentary, we
review recent findings from candidate approaches and unbiased screening methods
that provide initial insight into the cellular mechanisms of positioning and
their functional consequences. We highlight several specific mechanisms,
including tethering of genome regions to the nuclear periphery, passage through S
phase and histone modifications, that contribute to gene positioning in yeast,
plants and mammals.
PMID- 28404787
TI - A novel ATP-synthase-independent mechanism coupling mitochondrial activation to
exocytosis in insulin-secreting cells.
AB - Pancreatic beta-cells sense glucose, promoting insulin secretion. Glucose sensing
requires the sequential stimulation of glycolysis, mitochondrial metabolism and
Ca2+ entry. To elucidate how mitochondrial activation in beta-cells contributes
to insulin secretion, we compared the effects of glucose and the mitochondrial
substrate methylsuccinate in the INS-1E insulin-secreting cell line at the
respective concentrations at which they maximally activate mitochondrial
respiration. Both substrates induced insulin secretion with distinct respiratory
profiles, mitochondrial hyperpolarization, NADH production and ATP-to-ADP ratios.
In contrast to glucose, methylsuccinate failed to induce large [Ca2+] rises and
exocytosis proceeded largely independently of mitochondrial ATP synthesis. Both
glucose- and methylsuccinate-induced secretion was blocked by diazoxide,
indicating that Ca2+ is required for exocytosis. Dynamic assessment of the redox
state of mitochondrial thiols revealed a less marked reduction in response to
methylsuccinate than with glucose. Our results demonstrate that insulin
exocytosis can be promoted by two distinct mechanisms one of which is dependent
on mitochondrial ATP synthesis and large Ca2+ transients, and one of which is
independent of mitochondrial ATP synthesis and relies on small Ca2+ signals. We
propose that the combined effects of Ca2+ and redox reactions can trigger insulin
secretion by these two mechanisms.
PMID- 28404788
TI - SNAP-25 gene family members differentially support secretory vesicle fusion.
AB - Neuronal dense-core vesicles (DCVs) transport and secrete neuropeptides necessary
for development, plasticity and survival, but little is known about their fusion
mechanism. We show that Snap-25-null mutant (SNAP-25 KO) neurons, previously
shown to degenerate after 4 days in vitro (DIV), contain fewer DCVs and have
reduced DCV fusion probability in surviving neurons at DIV14. At DIV3, before
degeneration, SNAP-25 KO neurons show normal DCV fusion, but one day later fusion
is significantly reduced. To test if other SNAP homologs support DCV fusion, we
expressed SNAP-23, SNAP-29 or SNAP-47 in SNAP-25 KO neurons. SNAP-23 and SNAP-29
rescued viability and supported DCV fusion in SNAP-25 KO neurons, but SNAP-23 did
so more efficiently. SNAP-23 also rescued synaptic vesicle (SV) fusion while SNAP
29 did not. SNAP-47 failed to rescue viability and did not support DCV or SV
fusion. These data demonstrate a developmental switch, in hippocampal neurons
between DIV3 and DIV4, where DCV fusion becomes SNAP-25 dependent. Furthermore,
SNAP-25 homologs support DCV and SV fusion and neuronal viability to variable
extents - SNAP-23 most effectively, SNAP-29 less so and SNAP-47 ineffectively.
PMID- 28404789
TI - The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis.
AB - PP2A comprising B56 regulatory subunit isoforms (PP2AB56) is a serine/threonine
phosphatase essential for mitosis. At the kinetochore, PP2AB56 both stabilizes
microtubule binding and promotes silencing of the spindle assembly checkpoint
(SAC) through its association with the SAC protein BubR1. Cells depleted of the
B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing
APC/C (APC/CCdc20), which is an essential step for mitotic exit. It has been
hypothesized that this delay arises from increased production of the mitotic
checkpoint complex (MCC), an APC/CCdc20 inhibitor formed at unattached
kinetochores through SAC signaling. In contrast to this prediction, we show that
depletion of B56 subunits does not increase the amount or stability of the MCC.
Rather, delays in APC/CCdc20 activation in B56-depleted cells correlate with
impaired Cdc20 binding to APC/C. Stimulation of APC/CCdc20 assembly does not
require binding between PP2AB56 and BubR1, and thus this contribution of PP2AB56
towards mitotic exit is distinct from its functions at kinetochores. PP2AB56
associates with APC/C constitutively in a BubR1-independent manner. A mitotic
phosphorylation site on Cdc20, known to be a substrate of PP2AB56, modulates
APC/CCdc20 assembly. These results elucidate the contributions of PP2AB56 towards
completion of mitosis.
PMID- 28404791
TI - The effect of organic dust exposure on long-term change in lung function: a
systematic review and meta-analysis.
AB - Lung function is a predictor of morbidity and mortality, and the chronic nature
of lung function decline allows for preventive initiatives. Proinflammatory
constituents of organic dust are considered a possible cause of compromised
respiratory health. The aim of this systematic review was to reveal the impact of
organic dust exposure on long-term change in lung function. The literature search
was performed according to the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) criteria. Predefined criteria concerned study design:
longitudinal, >=1 year follow-up, >=50 exposed; exposure measures: organic dust,
measured or estimated, in different occupational settings; and outcome measures:
change in lung function measured by spirometry. Based on these criteria, 1580
potentially relevant publications were narrowed down to 20 included publications.
Quality was evaluated and discussed based on six objectively defined criteria.
Overall, 14 studies found some type of association between exposure to organic
dust and long-term change in lung function. However, the results were
inconsistent and no specific work exposure showed more clear associations to
change in lung function. Meta-analysis revealed an overall small significant
excess loss in forced expiratory volume in the 1st s for exposed compared with
controls of 4.92 mL/year (95% CI 0.14 to 9.69). No significant association was
seen overall for forced vital capacity. 12 studies revealed a significant
exposure-response relation between organic dust and change in lung function. The
results were inconsistent across varying study design and different exposure
measures and outcomes. We therefore conclude that there is limited evidence of a
causal association between general exposure to organic dust and long-term excess
decline in lung function.
PMID- 28404790
TI - Forest Soil Bacteria: Diversity, Involvement in Ecosystem Processes, and Response
to Global Change.
AB - The ecology of forest soils is an important field of research due to the role of
forests as carbon sinks. Consequently, a significant amount of information has
been accumulated concerning their ecology, especially for temperate and boreal
forests. Although most studies have focused on fungi, forest soil bacteria also
play important roles in this environment. In forest soils, bacteria inhabit
multiple habitats with specific properties, including bulk soil, rhizosphere,
litter, and deadwood habitats, where their communities are shaped by nutrient
availability and biotic interactions. Bacteria contribute to a range of essential
soil processes involved in the cycling of carbon, nitrogen, and phosphorus. They
take part in the decomposition of dead plant biomass and are highly important for
the decomposition of dead fungal mycelia. In rhizospheres of forest trees,
bacteria interact with plant roots and mycorrhizal fungi as commensalists or
mycorrhiza helpers. Bacteria also mediate multiple critical steps in the nitrogen
cycle, including N fixation. Bacterial communities in forest soils respond to the
effects of global change, such as climate warming, increased levels of carbon
dioxide, or anthropogenic nitrogen deposition. This response, however, often
reflects the specificities of each studied forest ecosystem, and it is still
impossible to fully incorporate bacteria into predictive models. The
understanding of bacterial ecology in forest soils has advanced dramatically in
recent years, but it is still incomplete. The exact extent of the contribution of
bacteria to forest ecosystem processes will be recognized only in the future,
when the activities of all soil community members are studied simultaneously.
PMID- 28404793
TI - High Reliability and 'Cargo Cult QI': response to Sutcliffe et al. BMJ Qual Saf
2017;26:248-51.
PMID- 28404794
TI - Neprosin, a Selective Prolyl Endoprotease for Bottom-up Proteomics and Histone
Mapping.
AB - Trypsin dominates bottom-up proteomics, but there are reasons to consider
alternative enzymes. Improving sequence coverage, exposing proteomic "dark
matter," and clustering post-translational modifications in different ways and
with higher-order drive the pursuit of reagents complementary to trypsin.
Additionally, enzymes that are easy to use and generate larger peptides that
capitalize upon newer fragmentation technologies should have a place in
proteomics. We expressed and characterized recombinant neprosin, a novel prolyl
endoprotease of the DUF239 family, which preferentially cleaves C-terminal to
proline residues under highly acidic conditions. Cleavage also occurs C-terminal
to alanine with some frequency, but with an intriguingly high "skipping rate."
Digestion proceeds to a stable end point, resulting in an average peptide mass of
2521 units and a higher dependence upon electron-transfer dissociation for
peptide-spectrum matches. In contrast to most proline-cleaving enzymes, neprosin
effectively degrades proteins of any size. For 1251 HeLa cell proteins identified
in common using trypsin, Lys-C, and neprosin, almost 50% of the neprosin sequence
contribution is unique. The high average peptide mass coupled with cleavage at
residues not usually modified provide new opportunities for profiling clusters of
post-translational modifications. We show that neprosin is a useful reagent for
reading epigenetic marks on histones. It generates peptide 1-38 of histone H3 and
peptide 1-32 of histone H4 in a single digest, permitting the analysis of co
occurring post-translational modifications in these important N-terminal tails.
PMID- 28404795
TI - Dynamics of the Interaction between Cotton Bollworm Helicoverpa armigera and
Nucleopolyhedrovirus as Revealed by Integrated Transcriptomic and Proteomic
Analyses.
AB - Over the past decades, Helicoverpa armigera nucleopolyhedrovirus (HearNPV) has
been widely used for biocontrol of cotton bollworm, which is one of the most
destructive pest insects in agriculture worldwide. However, the molecular
mechanism underlying the interaction between HearNPV and host insects remains
poorly understood. In this study, high-throughput RNA-sequencing was integrated
with label-free quantitative proteomics analysis to examine the dynamics of gene
expression in the fat body of H. armigera larvae in response to challenge with
HearNPV. RNA sequencing-based transcriptomic analysis indicated that host gene
expression was substantially altered, yielding 3,850 differentially expressed
genes (DEGs), whereas no global transcriptional shut-off effects were observed in
the fat body. Among the DEGs, 60 immunity-related genes were down-regulated after
baculovirus infection, a finding that was consistent with the results of
quantitative real-time RT-PCR. Gene ontology and functional classification
demonstrated that the majority of down-regulated genes were enriched in gene
cohorts involved in energy, carbohydrate, and amino acid metabolic pathways.
Proteomics analysis identified differentially expressed proteins in the fat body,
among which 76 were up-regulated, whereas 373 were significantly down-regulated
upon infection. The down-regulated proteins are involved in metabolic pathways
such as energy metabolism, carbohydrate metabolism (CM), and amino acid
metabolism, in agreement with the RNA-sequence data. Furthermore, correlation
analysis suggested a strong association between the mRNA level and protein
abundance in the H. armigera fat body. More importantly, the predicted gene
interaction network indicated that a large subset of metabolic networks was
significantly negatively regulated by viral infection, including CM-related
enzymes such as aldolase, enolase, malate dehydrogenase, and triose-phosphate
isomerase. Taken together, transcriptomic data combined with proteomic data
elucidated that baculovirus established systemic infection of host larvae and
manipulated the host mainly by suppressing the host immune response and down
regulating metabolism to allow viral self-replication and proliferation.
Therefore, this study provided important insights into the mechanism of host
baculovirus interaction.
PMID- 28404792
TI - Toxoplasma Effectors Targeting Host Signaling and Transcription.
AB - Early electron microscopy studies revealed the elaborate cellular features that
define the unique adaptations of apicomplexan parasites. Among these were bulbous
rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are
secreted during invasion of host cells. These early morphological studies were
followed by the exploration of the cellular contents of these secretory
organelles, revealing them to be comprised of highly divergent protein families
with few conserved domains or predicted functions. In parallel, studies on host
pathogen interactions identified many host signaling pathways that were
mysteriously altered by infection. It was only with the advent of forward and
reverse genetic strategies that the connections between individual parasite
effectors and the specific host pathways that they targeted finally became clear.
The current repertoire of parasite effectors includes ROP kinases and
pseudokinases that are secreted during invasion and that block host immune
pathways. Similarly, many secretory GRA proteins alter host gene expression by
activating host transcription factors, through modification of chromatin, or by
inducing small noncoding RNAs. These effectors highlight novel mechanisms by
which T. gondii has learned to harness host signaling to favor intracellular
survival and will guide future studies designed to uncover the additional
complexity of this intricate host-pathogen interaction.
PMID- 28404798
TI - Alterations of functional connectivity of the motor cortex in Fabry disease: An
RS-fMRI study.
AB - OBJECTIVE: To evaluate the presence of functional connectivity (FC) alterations
of the motor circuits in patients with Fabry disease (FD) and their possible
correlation with clinical variables with a resting-state (RS) fMRI analysis.
METHODS: In our cross-sectional study, 32 patients with FD with genetically
confirmed classic diagnosis of FD (12 men, mean age 43.3 +/- 12.2 years) were
enrolled along with 35 healthy controls (HCs) of comparable age and sex (14 men,
mean age 42.1 +/- 14.5 years). RS-fMRI data were analyzed with a seed-based
approach, with 2 different seeds for right and left motor cortex. Patients with
FD underwent a clinical examination for the assessment of different motor
functions. Correlations with clinical variables were probed with the Spearman
correlation coefficient. RESULTS: A reduction of FC was found in patients with FD
compared to HCs between both motor cortices and 2 clusters encompassing, for each
side, the caudate and lenticular nucleus (p < 5 * 10-4 and p < 10-8 for right and
left motor cortex, respectively) and between the left motor cortex and dentate
nuclei (p = 0.01) and Crus 1 in the right cerebellar hemisphere (p = 0.001). No
significant results emerged in tests for possible correlations of FC with
clinical scores. CONCLUSIONS: An alteration of the corticostriatal pathway is
present in FD, in line with the recently suggested subclinical involvement of
motor circuits in this disease. These results shed new light on the pattern of
cerebral involvement in FD.
PMID- 28404797
TI - Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced
immunomodulation against Trichuris muris infection.
AB - Despite the importance of the adjuvant in the immunization process, very few
adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic
vinyl sulfone (OVS) linked to the catalytic region of recombinant
serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis
(rPP2A) was used for intranasal immunization in mice previously infected with
Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a
reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The
immunohistochemical analysis of the intestinal sections showed that in immunized
animals with lipopeptide the mucus was significantly higher than in the other
experimental groups. Also, these animals presented significantly different
chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft
cells did not vary between groups, the intensity of fluorescence per cell was
significant in the group immunized with the rPP2A-OVS. The results of the present
study suggest that mice immunized with the lipopeptide are capable of activating
a combined Th17/Th9 response. This strategy of immunization may be of great
applicability not only in immunotherapy and immunoprophylaxis to control diseases
caused by nematodes but also in pathologies necessitating action at the level of
the Th9 response in the intestinal mucosa.
PMID- 28404796
TI - Tuning cancer fate: the unremitting role of host immunity.
AB - Host immunity plays a central and complex role in dictating tumour progression.
Solid tumours are commonly infiltrated by a large number of immune cells that
dynamically interact with the surrounding microenvironment. At first, innate and
adaptive immune cells successfully cooperate to eradicate microcolonies of
transformed cells. Concomitantly, surviving tumour clones start to proliferate
and harness immune responses by specifically hijacking anti-tumour effector
mechanisms and fostering the accumulation of immunosuppressive immune cell
subsets at the tumour site. This pliable interplay between immune and malignant
cells is a relentless process that has been concisely organized in three
different phases: elimination, equilibrium and escape. In this review, we aim to
depict the distinct immune cell subsets and immune-mediated responses
characterizing the tumour landscape throughout the three interconnected phases.
Importantly, the identification of key immune players and molecules involved in
the dynamic crosstalk between tumour and immune system has been crucial for the
introduction of reliable prognostic factors and effective therapeutic protocols
against cancers.
PMID- 28404799
TI - Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into
effect modifiers.
AB - OBJECTIVE: To examine the efficacy and effect modifiers of folic acid
supplementation in the prevention of stroke in regions without folic acid
fortification based on relevant, up-to-date published randomized trials. METHODS:
Relative risk (RR) was used to measure the effect of folic acid supplementation
on risk of stroke using a fixed effects model. FINDINGS: Overall, folic acid
supplementation significantly reduced the stroke risk by 11% (22 trials, n =
82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater
in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to
high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among
patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77
0.94) compared with those with folic acid fortification (7 trials, n = 14,655;
1.05, 0.90-1.23). In further stratified analyses among trials without folic acid
fortification, a larger beneficial effect was found in those trials that used a
low dosage of folic acid (<=0.8 mg: 0.78, 0.69-0.88) or low baseline vitamin B12
levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the
effect sizes were attenuated and insignificant (p for interaction <0.05 for
both). Although the interaction tests were not significant, there might be a
higher benefit in trials with a low dosage of vitamin B12, a low prevalence of
statin use, but a high prevalence of hypertension. CONCLUSIONS: Folic acid
supplementation could reduce the stroke risk in regions without folic acid
fortification, particularly in trials using a relatively low dosage of folic acid
and with low vitamin B12 levels.
PMID- 28404800
TI - Racial differences in statin adherence following hospital discharge for ischemic
stroke.
AB - OBJECTIVE: To compare nonadherence to statins in older black and white adults
following an ischemic stroke. METHODS: We studied black and white adults >=66
years of age with Medicare fee-for-service insurance coverage hospitalized for
ischemic stroke from 2007 to 2012 who filled a statin prescription within 30 days
following discharge. Nonadherence was defined as a proportion of days covered
<80% in the 365 days following hospital discharge. In addition, we evaluated
factors associated with nonadherence for white and black participants separately.
RESULTS: Overall 2,763 beneficiaries met the inclusion criteria (13.5% black).
Black adults were more likely than white adults to be nonadherent (49.7% vs
41.5%) even after adjustment for demographics, receipt of a low-income subsidy,
and baseline comorbidities (adjusted relative risk [RR] 1.14, 95% confidence
interval [CI] 1.01-1.29). Among white adults, receipt of a low-income subsidy
(adjusted RR 1.13, 95% CI 1.02-1.26), history of coronary heart disease (adjusted
RR 1.15, 95% CI 1.01-1.30), and discharge directly home following stroke
hospitalization (adjusted RR 1.26, 95% CI 1.10-1.44) were associated with a
higher risk of nonadherence. Among black adults, a 1-unit increase in the
Charlson comorbidity index (adjusted RR 1.04, 95% CI 1.01-1.09), history of
carotid artery disease (adjusted RR 2.38, 95% CI 1.08-5.25), and hospitalization
during the 365 days prior to the index stroke (adjusted RR 1.34, 95% CI 1.01
1.78) were associated with nonadherence. CONCLUSIONS: Compared with white adults,
black adults were more likely to be nonadherent to statins following
hospitalization for ischemic stroke.
PMID- 28404801
TI - Serum neurofilament light as a biomarker for mild traumatic brain injury in
contact sports.
AB - OBJECTIVE: To evaluate whether the axonal protein neurofilament light (NFL) in
serum is a sensitive biomarker to detect subtle brain injury or concussion in
contact sports athletes. METHODS: Two prospective cohort studies involving (1) 14
Swedish amateur boxers who underwent fluid biomarker assessments at 7-10 days
after bout and after 3 months of rest from boxing and (2) 35 Swedish professional
hockey players who underwent blood biomarker assessment at 1, 12, 36, and 144
hours after concussion and when the players returned to play were performed.
Fourteen healthy nonathletic controls and 12 athletic controls were also
enrolled. Serum NFL was measured using ultrasensitive single molecule array
technology. RESULTS: Serum NFL concentrations were increased in boxers 7-10 days
after bout as compared to the levels after 3 months rest as well as compared with
controls (p = 0.0007 and p < 0.0001, respectively). NFL decreased following 3
months of rest, but was still higher than in controls (p < 0.0001). Boxers who
received many (>15) hits to the head or were groggy after bout had higher
concentrations of serum NFL as compared to those who received fewer hits to the
head (p = 0.0023). Serum NFL increased over time in hockey players, and the
levels returned to normal at return to play. Importantly, serum NFL could
separate players with rapidly resolving postconcussion symptoms (PCS) from those
with prolonged PCS. CONCLUSIONS: The results from these 2 independent cohort
studies suggest that serum NFL is a highly sensitive biomarker for concussion.
PMID- 28404802
TI - Visual discrimination training improves Humphrey perimetry in chronic cortically
induced blindness.
AB - OBJECTIVE: To assess if visual discrimination training improves performance on
visual perimetry tests in chronic stroke patients with visual cortex involvement.
METHODS: 24-2 and 10-2 Humphrey visual fields were analyzed for 17 chronic
cortically blind stroke patients prior to and following visual discrimination
training, as well as in 5 untrained, cortically blind controls. Trained patients
practiced direction discrimination, orientation discrimination, or both, at
nonoverlapping, blind field locations. All pretraining and posttraining
discrimination performance and Humphrey fields were collected with online eye
tracking, ensuring gaze-contingent stimulus presentation. RESULTS: Trained
patients recovered ~108 degrees2 of vision on average, while untrained patients
spontaneously improved over an area of ~16 degrees2. Improvement was not affected
by patient age, time since lesion, size of initial deficit, or training type, but
was proportional to the amount of training performed. Untrained patients
counterbalanced their improvements with worsening of sensitivity over ~9 degrees2
of their visual field. Worsening was minimal in trained patients. Finally,
although discrimination performance improved at all trained locations, changes in
Humphrey sensitivity occurred both within trained regions and beyond, extending
over a larger area along the blind field border. CONCLUSIONS: In adults with
chronic cortical visual impairment, the blind field border appears to have
enhanced plastic potential, which can be recruited by gaze-controlled visual
discrimination training to expand the visible field. Our findings underscore a
critical need for future studies to measure the effects of vision restoration
approaches on perimetry in larger cohorts of patients.
PMID- 28404804
TI - Isocitrate dehydrogenase mutations: A biomarker for glioma-related excitability
and seizures.
PMID- 28404803
TI - Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer
disease.
AB - OBJECTIVE: To identify regional brain metabolic dysfunctions associated with
neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). METHODS:
We stratified 115 cognitively normal individuals into preclinical AD (both
amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid
or tau pathology present), or healthy controls (no amyloid or tau pathology
present) using [18F]florbetapir PET and CSF phosphorylated tau biomarkers.
Regression and voxel-based regression models evaluated the relationships between
baseline NPS measured by the Neuropsychiatric Inventory (NPI) and baseline and 2
year change in metabolism measured by [18F]fluorodeoxyglucose (FDG) PET. RESULTS:
Individuals with preclinical AD with higher NPI scores had higher [18F]FDG uptake
in the posterior cingulate cortex (PCC), ventromedial prefrontal cortex, and
right anterior insula at baseline. High NPI scores predicted subsequent
hypometabolism in the PCC over 2 years only in individuals with preclinical AD.
Sleep/nighttime behavior disorders and irritability and lability were the
components of the NPI that drove this metabolic dysfunction. CONCLUSIONS: The
magnitude of NPS in preclinical cases, driven by sleep behavior and irritability
domains, is linked to transitory metabolic dysfunctions within limbic networks
vulnerable to the AD process and predicts subsequent PCC hypometabolism. These
findings support an emerging conceptual framework in which NPS constitute an
early clinical manifestation of AD pathophysiology.
PMID- 28404806
TI - A blood test for concussion?
PMID- 28404805
TI - Mutant IDH1 and seizures in patients with glioma.
AB - OBJECTIVE: Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate
dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment
and is structurally similar to the excitatory neurotransmitter glutamate, we
sought to determine whether IDH1mut increases the risk of seizures in patients
with glioma, and whether D2HG increases the electrical activity of neurons.
METHODS: Three WHO grade II-IV glioma cohorts from separate institutions (total N
= 712) were retrospectively assessed for the presence of preoperative seizures
and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat
cortical neurons were grown on microelectrode arrays, and their electrical
activity was measured before and after treatment with exogenous D2HG, in the
presence or absence of the selective NMDA antagonist, AP5. RESULTS: Preoperative
seizures were observed in 18%-34% of IDH1 wild-type (IDH1wt) patients and in 59%
74% of IDH1mut patients (p < 0.001). Multivariable analysis, including WHO grade,
1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an
independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6
3.9, p < 0.001). Exogenous D2HG increased the firing rate of cultured rat
cortical neurons 4- to 6-fold, but was completely blocked by AP5. CONCLUSIONS:
The D2HG product of IDH1mut may increase neuronal activity by mimicking the
activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely
to cause seizures in patients. This has rapid translational implications for the
personalized management of tumor-associated epilepsy, as targeted IDH1mut
inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas.
PMID- 28404808
TI - Use of RS-fMRI in Fabry disease: Do we need it?
PMID- 28404807
TI - Body composition status and the risk of migraine: A meta-analysis.
AB - OBJECTIVE: To evaluate the association between migraine and body composition
status as estimated based on body mass index and WHO physical status categories.
METHODS: Systematic electronic database searches were conducted for relevant
studies. Two independent reviewers performed data extraction and quality
appraisal. Odds ratios (OR) and confidence intervals (CI) were pooled using a
random effects model. Significant values, weighted effect sizes, and tests of
homogeneity of variance were calculated. RESULTS: A total of 12 studies,
encompassing data from 288,981 unique participants, were included. The age- and
sex-adjusted pooled risk of migraine in those with obesity was increased by 27%
compared with those of normal weight (odds ratio [OR] 1.27; 95% confidence
interval [CI] 1.16-1.37, p < 0.001) and remained increased after multivariate
adjustments. Although the age- and sex-adjusted pooled migraine risk was
increased in overweight individuals (OR 1.08; 95% CI 1.04, 1.12, p < 0.001),
significance was lost after multivariate adjustments. The age- and sex-adjusted
pooled risk of migraine in underweight individuals was marginally increased by
13% compared with those of normal weight (OR 1.13; 95% CI 1.02, 1.24, p < 0.001)
and remained increased after multivariate adjustments. CONCLUSIONS: The current
body of evidence shows that the risk of migraine is increased in obese and
underweight individuals. Studies are needed to confirm whether interventions that
modify obesity status decrease the risk of migraine.
PMID- 28404809
TI - Choking on a foreign body: a physiological study of the effectiveness of
abdominal thrust manoeuvres to increase thoracic pressure.
AB - The Heimlich manoeuvre is a well-known intervention for the management of choking
due to foreign body airway occlusion, but the evidence base for guidance on this
topic is limited and guidelines differ. We measured pressures during abdominal
thrusts in healthy volunteers. The angle at which thrusts were performed
(upthrust vs circumferential) did not affect intrathoracic pressure. Self
administered abdominal thrusts produced similar pressures to those performed by
another person. Chair thrusts, where the subject pushed their upper abdomen
against a chair back, produced higher pressures than other manoeuvres. Both
approaches should be included in basic life support teaching.
PMID- 28404810
TI - GABAergic Networks in the Prefrontal Cortex and Working Memory.
PMID- 28404811
TI - Flexible Adaptation of Brain Networks during Stress.
PMID- 28404813
TI - Cycling our way to fit fat.
AB - Adipose tissue is increasingly being recognized as a key regulator of whole body
carbohydrate and lipid metabolism. In conditions of obesity and insulin
resistance mitochondrial content in this tissue is reduced, while treatment with
insulin sensitizing drugs such as thiazolidinediones (TZDs) increase
mitochondrial content. It has been known for decades that exercise increases
mitochondrial content in skeletal muscle and now several laboratories have shown
similar effects in adipose tissue. To date the specific mechanisms mediating this
effect have not been fully identified. In this review we highlight recent work
suggesting that increases in lipolysis and subsequently fatty acid re
esterification trigger the activation of 5' AMP-activated protein kinase (AMP)
activated protein kinase and ultimately the induction of mitochondrial
biogenesis. It is our current view that this pathway could be a unifying
mechanism linking numerous systemic factors (catecholamines, interleukin-6,
meteorin-like) to induction of mitochondrial biogenesis following exercise.
PMID- 28404814
TI - Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death
susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)
driven inflammatory disease.
AB - The X-linked inhibitor of apoptosis (XIAP) protein has been identified as a key
genetic driver of two distinct inflammatory disorders, X-linked
lymphoproliferative syndrome 2 (XLP-2) and very-early-onset inflammatory bowel
disease (VEO-IBD). Molecularly, the role of XIAP mutations in the pathogenesis of
these disorders is unclear. Recent work has consistently shown XIAP to be
critical for signaling downstream of the Crohn's disease susceptibility protein
nucleotide-binding oligomerization domain-containing 2 (NOD2); however, the
reported effects of XLP-2 and VEO-IBD XIAP mutations on cell death have been
inconsistent. In this manuscript, we describe a CRISPR-mediated genetic system
for cells of the myeloid lineage in which XIAP alleles can be replaced with
disease-associated XIAP variants expressed at endogenous levels to simultaneously
study inflammation-related cell death and NOD2 signaling. We show that,
consistent with previous studies, NOD2 signaling is critically dependent on the
BIR2 domain of XIAP. We further used this system to reconcile the aforementioned
inconsistent XIAP cell death data to show that XLP-2 and VEO-IBD XIAP mutations
that exhibit a loss-of-function NOD2 phenotype also lower the threshold for
inflammatory cell death. Last, we identified and studied three novel patient XIAP
mutations and used this system to characterize NOD2 and cell death phenotypes
driven by XIAP. The results of this work support the role of XIAP in mediating
NOD2 signaling while reconciling the role of XLP-2 and VEO-IBD XIAP mutations in
inflammatory cell death and provide a set of tools and framework to rapidly test
newly discovered XIAP variants.
PMID- 28404815
TI - The hepatokine FGF21 is crucial for peroxisome proliferator-activated receptor
alpha agonist-induced amelioration of metabolic disorders in obese mice.
AB - Obesity causes excess fat accumulation in white adipose tissues (WAT) and also in
other insulin-responsive organs such as the skeletal muscle, increasing the risk
for insulin resistance, which can lead to obesity-related metabolic disorders.
Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a master
regulator of fatty acid oxidation whose activator is known to improve
hyperlipidemia. However, the molecular mechanisms underlying PPARalpha activator
mediated reduction in adiposity and improvement of metabolic disorders are
largely unknown. In this study we investigated the effects of PPARalpha agonist
(fenofibrate) on glucose metabolism dysfunction in obese mice. Fenofibrate
treatment reduced adiposity and attenuated obesity-induced dysfunctions of
glucose metabolism in obese mice fed a high-fat diet. However, fenofibrate
treatment did not improve glucose metabolism in lipodystrophic A-Zip/F1 mice,
suggesting that adipose tissue is important for the fenofibrate-mediated
amelioration of glucose metabolism, although skeletal muscle actions could not be
completely excluded. Moreover, we investigated the role of the hepatokine
fibroblast growth factor 21 (FGF21), which regulates energy metabolism in adipose
tissue. In WAT of WT mice, but not of FGF21-deficient mice, fenofibrate enhanced
the expression of genes related to brown adipocyte functions, such as Ucp1,
Pgc1a, and Cpt1b Fenofibrate increased energy expenditure and attenuated obesity,
whole body insulin resistance, and adipocyte dysfunctions in WAT in high-fat-diet
fed WT mice but not in FGF21-deficient mice. These findings indicate that FGF21
is crucial for the fenofibrate-mediated improvement of whole body glucose
metabolism in obese mice via the amelioration of WAT dysfunctions.
PMID- 28404816
TI - The PICK1 Ca2+ sensor modulates N-methyl-d-aspartate (NMDA) receptor-dependent
microRNA-mediated translational repression in neurons.
AB - MicroRNAs (miRNAs) are important regulators of localized mRNA translation in
neuronal dendrites. The presence of RNA-induced silencing complex proteins in
these compartments and the dynamic miRNA expression changes that occur in
response to neuronal stimulation highlight their importance in synaptic
plasticity. Previously, we demonstrated a novel interaction between the major RNA
induced silencing complex component Argounaute-2 (Ago2) and the BAR
(bin/amphiphysin/rvs) domain protein PICK1. PICK1 recruits Ago2 to recycling
endosomes in dendrites, where it inhibits miRNA-mediated translational
repression. Chemical induction of long-term depression via NMDA receptor
activation causes the dissociation of Ago2 from PICK1 and a consequent increase
in dendritic miRNA-mediated gene silencing. The mechanism that underlies the
regulation of PICK1-Ago2 binding is unknown. In this study, we demonstrate that
the PICK1-Ago2 interaction is directly sensitive to Ca2+ ions so that high
[Ca2+]free reduces PICK1 binding to Ago2. Mutating a stretch of C-terminal Ca2+
binding residues in PICK1 results in a complete block of NMDA-induced PICK1-Ago2
disassociation in cortical neurons. Furthermore, the same mutant also blocks NMDA
stimulated miRNA-mediated gene silencing. This study defines a novel mechanism
whereby elevated [Ca2+] induced by NMDA receptor activation modulates Ago2 and
miRNA activity via PICK1. Our work suggests a Ca2+-dependent process to regulate
miRNA activity in neurons in response to the induction of long-term depression.
PMID- 28404817
TI - Hypoxia-inducible factor 1alpha predicts recurrence in high-grade soft tissue
sarcoma of extremities and trunk wall.
AB - BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show
abundant tumour stroma and presence of necrosis. In search for novel biomarkers
for personalised therapy, we determined the prognostic impact of stromal markers,
hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and
pleomorphic undifferentiated sarcoma. METHOD: We evaluated CD163, colony
stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)alpha
using immunohistochemical staining and assessed microvessel density using CD31 in
73 high-grade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the
extremities and the trunk wall. The results were correlated to metastasis-free
and overall survival. RESULTS: Expression of HIF-1alpha was associated with the
presence of necrosis and independently predicted shorter metastasis-free survival
(HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal
markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant
in this series. CONCLUSIONS: There is increasing evidence for the prognostic role
of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF
1alpha expression represents a candidate prognostic biomarker for clinical
application in high-grade leiomyosarcoma and undifferentiated pleomorphic
sarcoma.
PMID- 28404818
TI - Quantitative abilities in a reptile (Podarcis sicula).
AB - The ability to identify the largest amount of prey available is fundamental for
optimizing foraging behaviour in several species. To date, this cognitive skill
has been observed in all vertebrate groups except reptiles. In this study we
investigated the spontaneous ability of ruin lizards to select the larger amount
of food items. In Experiment 1, lizards proved able to select the larger food
item when presented with two alternatives differing in size (0.25, 0.50, 0.67 and
0.75 ratio). In Experiment 2 lizards presented with two groups of food items (1
versus 4, 2 versus 4, 2 versus 3 and 3 versus 4 items) were unable to select the
larger group in any contrast. The lack of discrimination in the presence of
multiple items represents an exception in numerical cognition studies, raising
the question as to whether reptiles' quantitative abilities are different from
those of other vertebrate groups.
PMID- 28404819
TI - Deimatism: a neglected component of antipredator defence.
AB - Deimatic or 'startle' displays cause a receiver to recoil reflexively in response
to a sudden change in sensory input. Deimatism is sometimes implicitly treated as
a form of aposematism (unprofitability associated with a signal). However, the
fundamental difference is, in order to provide protection, deimatism does not
require a predator to have any learned or innate aversion. Instead, deimatism can
confer a survival advantage by exploiting existing neural mechanisms in a way
that releases a reflexive response in the predator. We discuss the differences
among deimatism, aposematism, and forms of mimicry, and their ecological and
evolutionary implications. We highlight outstanding questions critical to
progress in understanding deimatism.
PMID- 28404820
TI - Increased food availability raises eviction rate in a cooperative breeding
mammal.
AB - In group-living mammals, the eviction of subordinate females from breeding groups
by dominants may serve to reduce feeding competition or to reduce breeding
competition. Here, we combined both correlational and experimental approaches to
investigate whether increases in food intake by dominant females reduces their
tendency to evict subordinate females in wild meerkats (Suricata suricatta). We
used 20 years of long-term data to examine the association between foraging
success and eviction rate, and provisioned dominant females during the second
half of their pregnancy, when they most commonly evict subordinates. We show that
rather than reducing the tendency for dominants to evict subordinates, foraging
success of dominant females is positively associated with the probability that
pregnant dominant females will evict subordinate females and that experimental
feeding increased their rates of eviction. Our results suggest that it is
unlikely that the eviction of subordinate females serves to reduce feeding
competition and that its principal function may be to reduce reproductive
competition. The increase in eviction rates following experimental feeding also
suggests that rather than feeding competition, energetic constraints may normally
constrain eviction rates.
PMID- 28404821
TI - A hypervariable mitochondrial protein coding sequence associated with
geographical origin in a cosmopolitan bloom-forming alga, Heterosigma akashiwo.
AB - Geographical distributions of phytoplankton species can be defined by events on
both evolutionary time and shorter scales, e.g. recent climate changes.
Additionally, modern industrial activity, including the transport of live fish
and spat for aquaculture and aquatic microorganisms in ship ballast water, may
aid the spread of phytoplankton. Obtaining a reliable marker is key to gaining
insight into the phylogeographic history of a species. Here, we report a
hypervariable mitochondrial gene in the cosmopolitan bloom-forming alga,
Heterosigma akashiwo We compared the entire mitochondrial genome sequences of
seven H. akashiwo strains from Japanese and North American coastal waters and
identified a hypervariable segment. The region codes for a hypothetical protein
with no defined function, and its variations between Japanese and North American
isolates were prominent, while the sequences were more conserved among Japanese
strains and North American isolates. Comparison of the sequence in isolates
obtained from different geographical points in the Northern Hemisphere revealed
that the sequence variations largely correlated with latitude and longitude (i.e.
Pacific/Atlantic oceans). Our results demonstrate the usefulness of the sequence
in determining the phylogeographic history of H. akashiwo.
PMID- 28404822
TI - Sperm as moderators of environmentally induced paternal effects in a livebearing
fish.
AB - Until recently, paternal effects-the influence of fathers on their offspring due
to environmental factors rather than genes-were largely discarded or assumed to
be confined to species exhibiting paternal care. It is now recognized that
paternal effects can be transmitted through the ejaculate, but unambiguous
evidence for them is scarce, because it is difficult to isolate effects operating
via changes to the ejaculate from maternal effects driven by female mate
assessment. Here, we use artificial insemination to disentangle mate assessment
from fertilization in guppies, and show that paternal effects can be transmitted
to offspring exclusively via ejaculates. We show that males fed reduced diets
produce poor-quality sperm and that offspring sired by such males (via artificial
insemination) exhibit reduced body size at birth. These findings may have
important implications for the many mating systems in which environmentally
induced changes in ejaculate quality have been reported.
PMID- 28404823
TI - Noise affects resource assessment in an invertebrate.
AB - Anthropogenic noise is a global pollutant, affecting animals across taxa.
However, how noise pollution affects resource acquisition is unknown. Hermit
crabs (Pagurus bernhardus) engage in detailed assessment and decision-making when
selecting a critical resource, their shell; this is crucial as individuals in
poor shells suffer lower reproductive success and higher mortality. We
experimentally exposed hermit crabs to anthropogenic noise during shell
selection. When exposed to noise, crabs approached the shell faster, spent less
time investigating it, and entered it faster. Our results demonstrate that
changes in the acoustic environment affect the behaviour of hermit crabs by
modifying the selection process of a vital resource. This is all the more
remarkable given that the known cues used in shell selection involve chemical,
visual and tactile sensory channels. Thus, our study provides rare evidence for a
cross-modal impact of noise pollution.
PMID- 28404824
TI - Glycolytic inhibition by 2-deoxy-d-glucose abolishes both neuronal and network
bursts in an in vitro seizure model.
AB - Neuronal activity is energy demanding and coupled to cellular metabolism. In this
study, we investigated the effects of glycolytic inhibition with 2-deoxy-d
glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and
epileptiform network bursts in hippocampal slices. The effect of glycolytic
inhibition on basal membrane properties was examined in hippocampal CA1 neurons,
which are not ordinarily active spontaneously. Intracellular application of 2-DG
did not significantly alter the membrane input resistance, action-potential
threshold, firing pattern, or input-output relationship of these neurons compared
with simultaneously recorded neighboring neurons without intracellular 2-DG. The
effect of glycolytic inhibition on neuronal firing was tested in spontaneously
active hippocampal neurons (CA3) when synaptic transmission was left intact or
blocked with AMPA, NMDA, and GABAA receptor antagonists (DNQX, APV, and
bicuculline, respectively). Under both conditions (synaptic activity intact or
blocked), bath application of 2-DG (2 mM) blocked spontaneous firing in ~2/3 (67
and 71%, respectively) of CA3 pyramidal neurons. In contrast, neuronal firing of
CA3 neurons persisted when 2-DG was applied intracellularly, suggesting that
glycolytic inhibition of individual neurons is not sufficient to stop neuronal
firing. The effects of 2-DG on epileptiform network bursts in area CA3 were
tested in Mg2+-free medium containing 50 uM 4-aminopyridine. Bath application of
2-DG abolished these epileptiform bursts in a dose-dependent and all-or-none
manner. Taken together, these data suggest that altered glucose metabolism
profoundly affects cellular and network hyperexcitability and that glycolytic
inhibition by 2-DG can effectively abrogate epileptiform activity.NEW &
NOTEWORTHY Neuronal activity is highly energy demanding and coupled to cellular
metabolism. In this study, we demonstrate that glycolytic inhibition with 2-deoxy
d-glucose (2-DG) effectively suppresses spontaneous neuronal firing and
epileptiform bursts in hippocampal slices. These data suggest that an altered
metabolic state can profoundly affect cellular and network excitability, and that
the glycolytic inhibitor 2-DG may hold promise as a novel treatment of drug
resistant epilepsy.
PMID- 28404825
TI - The cerebellum contributes to proprioception during motion.
AB - Proprioception, the sense of limb position and motion, is essential for
generating accurate movements. Limb position sense has typically been studied
under static conditions (i.e., the fixed position of a limb in space), with less
known about dynamic position sense (i.e., limb position during movement). Here we
investigated how a person's estimate of hand position varies when using spatial
or temporal information to judge the unseen hand's location during reaching. We
assessed the acuity of dynamic position sense in two directions, orthogonal to
hand movement, which only requires spatial information, and in line with hand
movement, which has both spatial and temporal components. Our results showed that
people have better proprioceptive acuity in the orthogonal condition where only
spatial information is used. We then assessed whether cerebellar damage impairs
proprioceptive acuity in both tasks during passive and active movement.
Cerebellar patients showed reduced acuity in both tasks and in both movement
conditions relative to age-matched controls. However, patients' deficits were
most apparent when judgments of active movement relied on temporal information.
Furthermore, both cerebellar patient and control performance correlated with the
trial-to-trial variability of their active movements: subjects are worse at the
proprioceptive tasks when movements are variable. Our results suggest that,
during active movements, proprioceptive acuity may be reliant on the motor
system's ability to predict motor output. Therefore, the resultant proprioceptive
deficits occurring after cerebellar damage may be related to a more general
impairment in movement prediction.NEW & NOTEWORTHY We assessed limb position
sense during movement in patients with cerebellar damage and found deficits in
proprioceptive acuity during both passive and active movement. The effect of
cerebellar damage was most apparent when individuals relied on both timing and
spatial information during active movement. Thus proprioceptive acuity during
active movements may be reliant on the motor system's ability to predict motor
output.
PMID- 28404826
TI - Multisensory coding in the multiple-demand regions: vibrotactile task information
is coded in frontoparietal cortex.
AB - At any given moment, our brains receive input from multiple senses. Successful
behavior depends on our ability to prioritize the most important information and
ignore the rest. A multiple-demand (MD) network of frontal and parietal regions
is thought to support this process by adjusting to code information that is
currently relevant (Duncan 2010). Accordingly, the network is proposed to encode
a range of different types of information, including perceptual stimuli, task
rules, and responses, as needed for the current cognitive operation. However,
most MD research has used visual tasks, leaving limited information about whether
these regions encode other sensory domains. We used multivoxel pattern analysis
(MVPA) of functional magnetic resonance imaging (fMRI) data to test whether the
MD regions code the details of somatosensory stimuli, in addition to tactile
motor response transformation rules and button-press responses. Participants
performed a stimulus-response task in which they discriminated between two
possible vibrotactile frequencies and applied a stimulus-response transformation
rule to generate a button-press response. For MD regions, we found significant
coding of tactile stimulus, rule, and response. Primary and secondary
somatosensory regions encoded the tactile stimuli and the button-press responses
but did not represent task rules. Our findings provide evidence that MD regions
can code nonvisual somatosensory task information, commensurate with a domain
general role in cognitive control.NEW & NOTEWORTHY How does the brain encode the
breadth of information from our senses and use this to produce goal-directed
behavior? A network of frontoparietal multiple-demand (MD) regions is implicated
but has been studied almost exclusively in the context of visual tasks. We used
multivariate pattern analysis of fMRI data to show that these regions encode
tactile stimulus information, rules, and responses. This provides evidence for a
domain-general role of the MD network in cognitive control.
PMID- 28404827
TI - New insights into vestibular-saccade interaction based on covert corrective
saccades in patients with unilateral vestibular deficits.
AB - In response to passive high-acceleration head impulses, patients with low
vestibulo-ocular reflex (VOR) gains often produce covert (executed while the head
is still moving) corrective saccades in the direction of deficient slow phases.
Here we examined 23 patients using passive, and 9 also active, head impulses with
acute (< 10 days from onset) unilateral vestibular neuritis and low VOR gains. We
found that when corrective saccades are larger than 10 degrees , the slow-phase
component of the VOR is inhibited, even though inhibition increases further the
time to reacquire the fixation target. We also found that 1) saccades are faster
and more accurate if the residual VOR gain is higher, 2) saccades also compensate
for the head displacement that occurs during the saccade, and 3) the amplitude
peak velocity relationship of the larger corrective saccades deviates from that
of head-fixed saccades of the same size. We propose a mathematical model to
account for these findings hypothesizing that covert saccades are driven by a
desired gaze position signal based on a prediction of head displacement using
vestibular and extravestibular signals, covert saccades are controlled by a gaze
feedback loop, and the VOR command is modulated according to predicted saccade
amplitude. A central and novel feature of the model is that the brain develops
two separate estimates of head rotation, one for generating saccades while the
head is moving and the other for generating slow phases. Furthermore, while the
model was developed for gaze-stabilizing behavior during passively induced head
impulses, it also simulates both active gaze-stabilizing and active gaze-shifting
eye movements.NEW & NOTEWORTHY During active or passive head impulses while
fixating stationary targets, low vestibulo-ocular gain subjects produce
corrective saccades when the head is still moving. The mechanisms driving these
covert saccades are poorly understood. We propose a mathematical model showing
that the brain develops two separate estimates of head rotation: a lower level
one, presumably in the vestibular nuclei, used to generate the slow-phase
component of the response, and a higher level one, within a gaze feedback loop,
used to drive corrective saccades.
PMID- 28404828
TI - Interaction of compass sensing and object-motion detection in the locust central
complex.
AB - Goal-directed behavior is often complicated by unpredictable events, such as the
appearance of a predator during directed locomotion. This situation requires
adaptive responses like evasive maneuvers followed by subsequent reorientation
and course correction. Here we study the possible neural underpinnings of such a
situation in an insect, the desert locust. As in other insects, its sense of
spatial orientation strongly relies on the central complex, a group of midline
brain neuropils. The central complex houses sky compass cells that signal the
polarization plane of skylight and thus indicate the animal's steering direction
relative to the sun. Most of these cells additionally respond to small moving
objects that drive fast sensory-motor circuits for escape. Here we investigate
how the presentation of a moving object influences activity of the neurons during
compass signaling. Cells responded in one of two ways: in some neurons, responses
to the moving object were simply added to the compass response that had adapted
during continuous stimulation by stationary polarized light. By contrast, other
neurons disadapted, i.e., regained their full compass response to polarized
light, when a moving object was presented. We propose that the latter case could
help to prepare for reorientation of the animal after escape. A neuronal network
based on central-complex architecture can explain both responses by slight
changes in the dynamics and amplitudes of adaptation to polarized light in CL
columnar input neurons of the system.NEW & NOTEWORTHY Neurons of the central
complex in several insects signal compass directions through sensitivity to the
sky polarization pattern. In locusts, these neurons also respond to moving
objects. We show here that during polarized-light presentation, responses to
moving objects override their compass signaling or restore adapted inhibitory as
well as excitatory compass responses. A network model is presented to explain the
variations of these responses that likely serve to redirect flight or walking
following evasive maneuvers.
PMID- 28404830
TI - Implications of plan-based generalization in sensorimotor adaptation.
AB - Generalization is a fundamental aspect of behavior, allowing for the transfer of
knowledge from one context to another. The details of this transfer are thought
to reveal how the brain represents what it learns. Generalization has been a
central focus in studies of sensorimotor adaptation, and its pattern has been
well characterized: Learning of new dynamic and kinematic transformations in one
region of space tapers off in a Gaussian-like fashion to neighboring untrained
regions, echoing tuned population codes in the brain. In contrast to common
allusions to generalization in cognitive science, generalization in visually
guided reaching is usually framed as a passive consequence of neural tuning
functions rather than a cognitive feature of learning. While previous research
has presumed that maximum generalization occurs at the instructed task goal or
the actual movement direction, recent work suggests that maximum generalization
may occur at the location of an explicitly accessible movement plan. Here we
provide further support for plan-based generalization, formalize this theory in
an updated model of adaptation, and test several unexpected implications of the
model. First, we employ a generalization paradigm to parameterize the
generalization function and ascertain its maximum point. We then apply the
derived generalization function to our model and successfully simulate and fit
the time course of implicit adaptation across three behavioral experiments. We
find that dynamics predicted by plan-based generalization are borne out in the
data, are contrary to what traditional models predict, and lead to surprising
implications for the behavioral, computational, and neural characteristics of
sensorimotor adaptation.NEW & NOTEWORTHY The pattern of generalization is thought
to reveal how the motor system represents learned actions. Recent work has made
the intriguing suggestion that maximum generalization in sensorimotor adaptation
tasks occurs at the location of the learned movement plan. Here we support this
interpretation, develop a novel model of motor adaptation that incorporates plan
based generalization, and use the model to successfully predict surprising
dynamics in the time course of adaptation across several conditions.
PMID- 28404831
TI - Do Vulnerable Populations Consume Adequate Amounts of Dietary Protein?
PMID- 28404832
TI - Folate Deficiency Is Prevalent in Women of Childbearing Age in Belize and Is
Negatively Affected by Coexisting Vitamin B-12 Deficiency: Belize National
Micronutrient Survey 2011.
AB - Background: Folate deficiency, vitamin B-12 deficiency, and anemia can have
adverse effects on birth outcomes. Also, low vitamin B-12 reduces the formation
of metabolically active folate.Objectives: We sought to establish the baseline
prevalence of and factors associated with folate deficiency and insufficiency,
vitamin B-12 deficiency, and anemia among women of childbearing age (WCBA) in
Belize.Methods: In 2011, a national probability-based survey was completed among
Belizean nonpregnant WCBA aged 15-49 y. Blood samples for determination of
hemoglobin, folate (RBC and serum), and vitamin B-12 (plasma) and
sociodemographic and health information were collected from 937 women. RBC and
serum folate concentrations were measured by microbiologic assay (MBA). Folate
status was defined based on both the WHO-recommended radioproteinbinding assay
and the assay adjusted for the MBA.Results: The national prevalence estimates for
folate deficiency in WCBA, based on serum and RBC folate concentrations by using
the assay-matched cutoffs, were 11.0% (95% CI: 8.6%, 14.0%) and 35.1% (95% CI:
31.3%, 39.2%), respectively. By using the assay-matched compared with the WHO
recommended cutoffs, a substantially higher prevalence of folate deficiency was
observed based on serum (6.9% absolute difference) and RBC folate (28.9% absolute
difference) concentrations. The prevalence for RBC folate insufficiency was 48.9%
(95% CI: 44.8%, 53.1%). Prevalence estimates for vitamin B-12 deficiency and
marginal deficiency and anemia were 17.2% (95% CI: 14.2%, 20.6%), 33.2% (95% CI:
29.6%, 37.1%), and 22.7% (95% CI: 19.5%, 26.2%), respectively. The adjusted
geometric means of the RBC folate concentration increased significantly (P-trend
< 0.001) in WCBA who had normal vitamin B-12 status relative to WCBA who were
vitamin B-12 deficient.Conclusions: In Belize, the prevalence of folate and
vitamin B-12 deficiencies continues to be a public health concern among WCBA.
Furthermore, low folate status co-occurred with low vitamin B-12 status,
underlining the importance of providing adequate vitamin B-12 and folic acid
intake through approaches such as mandatory food fortification.
PMID- 28404829
TI - Neural mechanisms of oculomotor abnormalities in the infantile strabismus
syndrome.
AB - Infantile strabismus is characterized by numerous visual and oculomotor
abnormalities. Recently nonhuman primate models of infantile strabismus have been
established, with characteristics that closely match those observed in human
patients. This has made it possible to study the neural basis for visual and
oculomotor symptoms in infantile strabismus. In this review, we consider the
available evidence for neural abnormalities in structures related to oculomotor
pathways ranging from visual cortex to oculomotor nuclei. These studies provide
compelling evidence that a disturbance of binocular vision during a sensitive
period early in life, whatever the cause, results in a cascade of abnormalities
through numerous brain areas involved in visual functions and eye movements.
PMID- 28404833
TI - Evaluation of Simulation Models that Estimate the Effect of Dietary Strategies on
Nutritional Intake: A Systematic Review.
AB - Background: Dietary simulation modeling can predict dietary strategies that may
improve nutritional or health outcomes.Objectives: The study aims were to
undertake a systematic review of simulation studies that model dietary strategies
aiming to improve nutritional intake, body weight, and related chronic disease,
and to assess the methodologic and reporting quality of these models.Methods: The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided the
search strategy with studies located through electronic searches [Cochrane
Library, Ovid (MEDLINE and Embase), EBSCOhost (CINAHL), and Scopus]. Study
findings were described and dietary modeling methodology and reporting quality
were critiqued by using a set of quality criteria adapted for dietary modeling
from general modeling guidelines.Results: Forty-five studies were included and
categorized as modeling moderation, substitution, reformulation, or promotion
dietary strategies. Moderation and reformulation strategies targeted individual
nutrients or foods to theoretically improve one particular nutrient or health
outcome, estimating small to modest improvements. Substituting unhealthy foods
with healthier choices was estimated to be effective across a range of nutrients,
including an estimated reduction in intake of saturated fatty acids, sodium, and
added sugar. Promotion of fruits and vegetables predicted marginal changes in
intake. Overall, the quality of the studies was moderate to high, with certain
features of the quality criteria consistently reported.Conclusions: Based on the
results of reviewed simulation dietary modeling studies, targeting a variety of
foods rather than individual foods or nutrients theoretically appears most
effective in estimating improvements in nutritional intake, particularly reducing
intake of nutrients commonly consumed in excess. A combination of strategies
could theoretically be used to deliver the best improvement in outcomes. Study
quality was moderate to high. However, given the lack of dietary simulation
reporting guidelines, future work could refine the quality tool to harmonize
consistency in the reporting of subsequent dietary modeling studies.
PMID- 28404835
TI - Coverage and Utilization in Food Fortification Programs: Critical and Neglected
Areas of Evaluation.
AB - The need for evidence to inform nutrition program design and implementation has
long been recognized, yet the generation and use of evidence for program decision
making has lagged. The results of the coverage surveys reported in this
supplement highlight some of the strengths and areas for improvement of current
population-based (i.e., staple foods and condiments) and targeted (e.g., foods
for infants and young children) fortification programs. Among other topics, the
results identify a few striking successful fortification programs whereby the
majority of the food vehicle used is fortifiable and fortified, and coverage is
equitable among those classified as vulnerable and not. Other programs have great
potential based on very high use of a fortifiable food vehicle, including in most
cases among the vulnerable, but that potential is not currently reached because
of low compliance with fortification requirements. Programs were also identified
whereby the food vehicle has limited potential to make public health
contributions to micronutrient intake, given the low proportions of the
population who consume the food vehicle in general or who consume the fortifiable
food vehicle. Four key lessons were learned: 1) the potential for impact of food
fortification depends on the appropriate choice of food fortification vehicle but
also on the proportion of the food vehicle consumed that is fortifiable; 2) the
design of fortification programs should be informed by the magnitude and
distribution of inadequate intake and deficiency and consumption of fortifiable
foods, and part of micronutrient deficiency control strategies to ensure
coordination with other programs; 3) effective quality control of fortification
levels in foods urgently needs strengthening, including the many governance and
other policy factors that influence the capacity, resources, and commitment to do
this; 4) periodic review of the assumptions related to dietary patterns that
underpin food fortification is needed to ensure continual safe and impactful
programs.
PMID- 28404834
TI - Promotion of Orange-Fleshed Sweet Potato Increased Vitamin A Intakes and Reduced
the Odds of Low Retinol-Binding Protein among Postpartum Kenyan Women.
AB - Background: Orange-fleshed sweet potato (OFSP) improves vitamin A (VA) status of
young children; research with pregnant and lactating women is limited.Objective:
We examined the effectiveness of the Mama SASHA (Sweetpotato Action for Security
and Health in Africa) program to improve nutrition knowledge, diets, and
nutritional status of pregnant and lactating women (PLW) in Western
Kenya.Methods: Eight health facilities were allocated to the Mama SASHA
intervention or comparison arms. PLW in intervention facilities received enhanced
nutrition counseling at health clinics, were linked with community-based maternal
support groups, and received vouchers for OFSP vine cuttings. Control PLW
received clinic-based nutrition counseling only. A total of 505 women in early
and midpregnancy, attending their first antenatal care visit, and with no
previous engagement in project activities were enrolled from the 8 facilities.
Nutrition and health-seeking knowledge, food security, dietary patterns, and
anthropometric measurements were collected at 4 time points at <=9 mo postpartum.
VA intakes were assessed with multipass 24-h recalls in a subsample of 206
mothers at 8-10 mo postpartum. VA status was assessed by using serum retinol
binding protein (RBP). Impacts were estimated with multilevel mixed models
adjusted for clustering and differences at enrollment.Results: At enrollment,
22.9% of women had RBP <1.17 MUmol/L. By 9 mo postpartum, intervention women had
significantly higher intakes of VA [adjusted difference = 297.0 retinol activity
equivalent (RAE) units; 95% CI: 82, 513 RAE units; P = 0.01; n = 206], greater
consumption of VA-rich fruit and vegetables in the previous 7 d (difference-in
difference estimate: 0.40 d; 95% CI: 0.23, 0.56 d; P < 0.01), and a 45% reduction
in the odds of RBP <1.17 MUmol/L (OR: 0.55; 95% CI: 0.33, 0.92; P =
0.01).Conclusion: Promotion of OFSP to PLW through health services is a feasible
strategy to improve women's nutrition knowledge, VA intakes, and maternal RBP.
PMID- 28404836
TI - Coverage of Large-Scale Food Fortification of Edible Oil, Wheat Flour, and Maize
Flour Varies Greatly by Vehicle and Country but Is Consistently Lower among the
Most Vulnerable: Results from Coverage Surveys in 8 Countries.
AB - Background: Large-scale food fortification (LSFF) of commonly consumed food
vehicles is widely implemented in low- and middle-income countries. Many programs
have monitoring information gaps and most countries fail to assess program
coverage.Objective: The aim of this work was to present LSFF coverage survey
findings (overall and in vulnerable populations) from 18 programs (7 wheat flour,
4 maize flour, and 7 edible oil programs) conducted in 8 countries between 2013
and 2015.Methods: A Fortification Assessment Coverage Toolkit (FACT) was
developed to standardize the assessments. Three indicators were used to assess
the relations between coverage and vulnerability: 1) poverty, 2) poor dietary
diversity, and 3) rural residence. Three measures of coverage were assessed: 1)
consumption of the vehicle, 2) consumption of a fortifiable vehicle, and 3)
consumption of a fortified vehicle. Individual program performance was assessed
based on the following: 1) achieving overall coverage >=50%, 2) achieving
coverage of >=75% in >=1 vulnerable group, and 3) achieving equity in coverage
for >=1 vulnerable group.Results: Coverage varied widely by food vehicle and
country. Only 2 of the 18 LSFF programs assessed met all 3 program performance
criteria. The 2 main program bottlenecks were a poor choice of vehicle and
failure to fortify a fortifiable vehicle (i.e., absence of
fortification).Conclusions: The results highlight the importance of sound program
design and routine monitoring and evaluation. There is strong evidence of the
impact and cost-effectiveness of LSFF; however, impact can only be achieved when
the necessary activities and processes during program design and implementation
are followed. The FACT approach fills an important gap in the availability of
standardized tools. The LSFF programs assessed here need to be re-evaluated to
determine whether to further invest in the programs, whether other vehicles are
appropriate, and whether other approaches are needed.
PMID- 28404837
TI - Preserving Mother Nature's Best Food for Preterm Infants.
PMID- 28404838
TI - Assessing Coverage of Population-Based and Targeted Fortification Programs with
the Use of the Fortification Assessment Coverage Toolkit (FACT): Background,
Toolkit Development, and Supplement Overview.
AB - Food fortification is a widely used approach to increase micronutrient intake in
the diet. High coverage is essential for achieving impact. Data on coverage is
limited in many countries, and tools to assess coverage of fortification programs
have not been standardized. In 2013, the Global Alliance for Improved Nutrition
developed the Fortification Assessment Coverage Toolkit (FACT) to carry out
coverage assessments in both population-based (i.e., staple foods and/or
condiments) and targeted (e.g., infant and young child) fortification programs.
The toolkit was designed to generate evidence on program coverage and the use of
fortified foods to provide timely and programmatically relevant information for
decision making. This supplement presents results from FACT surveys that assessed
the coverage of population-based and targeted food fortification programs across
14 countries. It then discusses the policy and program implications of the
findings for the potential for impact and program improvement.
PMID- 28404839
TI - Coverage of Nutrition Interventions Intended for Infants and Young Children
Varies Greatly across Programs: Results from Coverage Surveys in 5 Countries.
AB - Background: The efficacy of a number of interventions that include fortified
complementary foods (FCFs) or other products to improve infant and young child
feeding (IYCF) is well established. Programs that provide such products free or
at a subsidized price are implemented in many countries around the world.
Demonstrating the impact at scale of these programs has been challenging, and
rigorous information on coverage and utilization is lacking.Objective: The
objective of this article is to review key findings from 11 coverage surveys of
IYCF programs distributing or selling FCFs or micronutrient powders in 5
countries.Methods: Programs were implemented in Ghana, Cote d'Ivoire, India,
Bangladesh, and Vietnam. Surveys were implemented at different stages of program
implementation between 2013 and 2015. The Fortification Assessment Coverage
Toolkit (FACT) was developed to assess 3 levels of coverage (message: awareness
of the product; contact: use of the product >=1 time; and effective: regular use
aligned with program-specific goals), as well as barriers and factors that
facilitate coverage. Analyses included the coverage estimates, as well as an
assessment of equity of coverage between the poor and nonpoor, and between those
with poor and adequate child feeding practices.Results: Coverage varied greatly
between countries and program models. Message coverage ranged from 29.0% to
99.7%, contact coverage from 22.6% to 94.4%, and effective coverage from 0.8% to
88.3%. Beyond creating awareness, programs that achieved high coverage were those
with effective mechanisms in place to overcome barriers for both supply and
demand.Conclusions: Variability in coverage was likely due to the program design,
delivery model, quality of implementation, and product type. Measuring program
coverage and understanding its determinants is essential for program improvement
and to estimate the potential for impact of programs at scale. Use of the FACT
can help overcome this evidence gap.
PMID- 28404840
TI - Household Coverage with Adequately Iodized Salt Varies Greatly between Countries
and by Residence Type and Socioeconomic Status within Countries: Results from 10
National Coverage Surveys.
AB - Background: Household coverage with iodized salt was assessed in 10 countries
that implemented Universal Salt Iodization (USI).Objective: The objective of this
paper was to summarize household coverage data for iodized salt, including the
relation between coverage and residence type and socioeconomic status
(SES).Methods: A review was conducted of results from cross-sectional multistage
household cluster surveys with the use of stratified probability proportional to
size design in Bangladesh, Ethiopia, Ghana, India, Indonesia, Niger, the
Philippines, Senegal, Tanzania, and Uganda. Salt iodine content was assessed with
quantitative methods in all cases. The primary indicator of coverage was
percentage of households that used adequately iodized salt, with an additional
indicator for salt with some added iodine. Indicators of risk were SES and
residence type. We used 95% CIs to determine significant differences in
coverage.Results: National household coverage of adequately iodized salt varied
from 6.2% in Niger to 97.0% in Uganda. For salt with some added iodine, coverage
varied from 52.4% in the Philippines to 99.5% in Uganda. Coverage with adequately
iodized salt was significantly higher in urban than in rural households in
Bangladesh (68.9% compared with 44.3%, respectively), India (86.4% compared with
69.8%, respectively), Indonesia (59.3% compared with 51.4%, respectively), the
Philippines (31.5% compared with 20.2%, respectively), Senegal (53.3% compared
with 19.0%, respectively), and Tanzania (89.2% compared with 57.6%,
respectively). In 7 of 8 countries with data, household coverage of adequately
iodized salt was significantly higher in high- than in low-SES households in
Bangladesh (58.8% compared with 39.7%, respectively), Ghana (36.2% compared with
21.5%, respectively), India (80.6% compared with 70.5%, respectively), Indonesia
(59.9% compared with 45.6%, respectively), the Philippines (39.4% compared with
17.3%, respectively), Senegal (50.7% compared with 27.6%, respectively) and
Tanzania (80.9% compared with 51.3%, respectively).Conclusions: Uganda has
achieved USI. In other countries, access to iodized salt is inequitable. Quality
control and regulatory enforcement of salt iodization remain challenging. Notable
progress toward USI has been made in Ethiopia and India. Assessing progress
toward USI only through household salt does not account for potentially iodized
salt consumed through processed foods.
PMID- 28404841
TI - MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double
Blind, Placebo-Controlled, Cross-Over Trial.
AB - BACKGROUND AND PURPOSE: This study aimed to assess the efficacy of modafinil, a
wakefulness-promoting agent in alleviating post-stroke fatigue >=3 months after
stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result
in reduced symptoms of fatigue compared with placebo. METHODS: This single-center
phase 2 trial used a randomized, double-blind, placebo-controlled, crossover
design. The key inclusion criterion was a multidimensional fatigue inventory
score of >=60. Patients were randomized to either modafinil or placebo for 6
weeks of therapy, then after a 1 week washout period swapped treatment arms for a
second 6 weeks of therapy. The primary outcome was the multidimensional fatigue
inventory; secondary outcomes included the Montreal cognitive assessment, the
Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of
Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered
questionnaire with a range of 0 to 100. Treatment efficacy was assessed using
linear regression by estimating within-person, baseline-adjusted differences in
mean outcomes after therapy. This trial was registered with the Australian New
Zealand Clinical Trials Registry (ACTRN12615000350527). RESULTS: A total of 232
stroke survivors were screened and 36 were randomized. Participants receiving
modafinil reported a significant decrease in fatigue (multidimensional fatigue
inventory, -7.38; 95% CI, -21.76 to -2.99; P<0.001) and improved quality of life
(SSQoL, 11.81; 95% CI, 2.31 to 21.31; P=0.0148) compared with placebo. Montreal
cognitive assessment and DASS were not significantly improved with modafinil
therapy during the study period (P>0.05). CONCLUSIONS: Stroke survivors with
nonresolving fatigue reported reduced fatigue and improved quality of life after
taking 200 mg daily treatment with modafinil. CLINICAL TRIAL REGISTRATION: URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique
identifier: ACTRN12615000350527.
PMID- 28404842
TI - An Immortalized Human Dorsal Root Ganglion Cell Line Provides a Novel Context To
Study Herpes Simplex Virus 1 Latency and Reactivation.
AB - A defining characteristic of alphaherpesviruses is the establishment of lifelong
latency in host sensory ganglia with occasional reactivation causing recurrent
lytic infections. As an alternative to rodent models, we explored the use of an
immortalized cell line derived from human dorsal root ganglia. HD10.6 cells
proliferate by virtue of a transduced tetracycline-regulated v-myc oncogene. In
the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology
and express sensory neuron-associated markers such as neurotrophin receptors
TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin. Infection of
mature HD10.6 neurons by herpes simplex virus 1 (HSV-1) results in a delayed but
productive infection. However, infection at a low multiplicity of infection (MOI)
in the presence of acyclovir results in a quiescent infection resembling latency
in which viral genomes are retained in a low number of neurons, viral gene
expression is minimal, and infectious virus is not released. At least some of the
quiescent viral genomes retain the capacity to reactivate, resulting in viral DNA
replication and release of infectious virus. Reactivation can be induced by
depletion of nerve growth factor; other commonly used reactivation stimuli have
no significant effect.IMPORTANCE Infections by herpes simplex viruses (HSV) cause
painful cold sores or genital lesions in many people; less often, they affect the
eye or even the brain. After the initial infection, the virus remains inactive or
latent in nerve cells that sense the region where that infection occurred. To
learn how virus maintains and reactivates from latency, studies are done in
neurons taken from rodents or in whole animals to preserve the full context of
infection. However, some cellular mechanisms involved in HSV infection in rodents
are different from those in humans. We describe the use of a human cell line that
has the properties of a sensory neuron. HSV infection in these cultured cells
shows the properties expected for a latent infection, including reactivation to
produce newly infectious virus. Thus, we now have a cell culture model for
latency that is derived from the normal host for this virus.
PMID- 28404843
TI - Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis
after Severe Acute Respiratory Syndrome Coronavirus Infection.
AB - Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic
respiratory virus that causes morbidity and mortality in humans. After infection
with SARS-CoV, the acute lung injury caused by the virus must be repaired to
regain lung function. A dysregulation in this wound healing process leads to
fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF),
with higher prevalence in older patients. Using mouse models of SARS-CoV
pathogenesis, we have identified that the wound repair pathway, controlled by the
epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV
induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice],
we find that SARS-CoV infection causes enhanced lung disease. Importantly, we
show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF
like growth factor (HB-EGF) are upregulated, and exogenous addition of these
ligands during infection leads to enhanced lung disease and altered wound healing
dynamics. Our data demonstrate a key role of EGFR in the host response to SARS
CoV and how it may be implicated in lung disease induced by other highly
pathogenic respiratory viruses.IMPORTANCE PF has many causative triggers,
including severe respiratory viruses such as SARS-CoV. Currently there are no
treatments to prevent the onset or limit the progression of PF, and the molecular
pathways underlying the development of PF are not well understood. In this study,
we identified a role for the balanced control of EGFR signaling as a key factor
in progression to PF. These data demonstrate that therapeutic treatment
modulating EGFR activation could protect against PF development caused by severe
respiratory virus infection.
PMID- 28404844
TI - Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus
1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D
Generates Anti-EHV-1 Immune Responses in Mice.
AB - Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1)
infection, and several different strategies of vaccination have been investigated
and developed over the past few decades. Herein, we report that the live
attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been
shown to be unable to enter into neurons and establish latency in mice, can be
utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD)
and that the intramuscular immunization of mice results in strong antiviral
humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was
constructed by inserting an EHV-1 gD expression cassette under the control of the
cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV
1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through
intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the
commercially available vaccine Vetera EHVXP 1/4 (Vetera; Boehringer Ingelheim
Vetmedica) resulted in the production of neutralizing antibodies, the levels of
which were significantly higher in comparison to those in VC2- and mock
vaccinated animals (P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG
subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated
robust IgG1 and IgG2a antibodies after three vaccinations (P < 0.001).
Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM
than mice in the other groups before and after challenge (P < 0.01 or P < 0.05).
Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses,
characterized by the upregulation of both interferon- and tumor necrosis factor
positive CD4+ T cells and CD8+ T cells. Overall, the data suggest that the HSV-1
VC2 vaccine strain may be used as a viral vector for the vaccination of horses as
well as, potentially, for the vaccination of other economically important
animals.IMPORTANCE A novel virus-vectored VC2-EHV-1-gD vaccine was constructed
using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated
strong humoral and cellular immune responses in mice, suggesting that it could
protect horses against EHV-1 infection.
PMID- 28404845
TI - Molecular Evolution and Emergence of H5N6 Avian Influenza Virus in Central China.
AB - H5N6 avian influenza virus (AIV) has posed a potential threat to public health
since its emergence in China in 2013. To understand the evolution and emergence
of H5N6 AIV in the avian population, we performed molecular surveillance of live
poultry markets (LPMs) in Wugang Prefecture, Hunan Province, in central China,
during 2014 and 2015. Wugang Prefecture is located on the Eastern Asian
Australian migratory bird flyway, and a human death due to an H5N6 virus was
reported in the prefecture on 21 November 2016. In total, we sampled and
sequenced the complete genomes of 175 H5N6 AIVs. Notably, our analysis revealed
that H5N6 AIVs contain at least six genotypes arising from segment reassortment,
including a rare variant that possesses an HA gene derived from H5N1 clade 2.3.2
and a novel NP gene that has its origins with H7N3 viruses. In addition,
phylogenetic analysis revealed that genetically similar H5N6 AIVs tend to cluster
according to their geographic regions of origin. These results help to reveal the
evolutionary behavior of influenza viruses prior to their emergence in
humans.IMPORTANCE The newly emerged H5N6 influenza A virus has caused more than
10 human deaths in China since 2013. In November 2016, a human death due to an
H5N6 virus, in Wugang Prefecture, Hunan Province, was confirmed by the WHO. To
better understand the evolution and emergence of H5N6 viruses, we surveyed live
poultry markets (LPMs) in Wugang Prefecture before the reported human death, with
a focus on revealing the diversity and genomic origins of H5N6 in birds during
2014 and 2015. In general, H5N6 viruses in this region were most closely related
to H5N1 clade 2.3.4.4, with the exception of one virus with an HA gene derived
from clade 2.3.2 such that it represents a novel reassortant. Clearly, the
ongoing surveillance of LPMs is central to monitoring the emergence of pathogenic
influenza viruses.
PMID- 28404846
TI - Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza
Virus by Suppressing Beta Interferon Production.
AB - The high mutation rates of the influenza virus genome facilitate the generation
of viral escape mutants, rendering vaccines and drugs against influenza virus
encoded targets potentially ineffective. Therefore, we identified host cell
determinants dispensable for the host but crucial for virus replication, with the
goal of preventing viral escape and finding effective antivirals. To identify
these host factors, we screened 2,732 human genes using RNA interference and
focused on one of the identified host factors, the double plant homeodomain
fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in
cells infected with influenza virus resulted in decreased expression of viral
proteins and RNA. Furthermore, production of progeny virus was reduced by two
logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was
involved in the replication of seasonal influenza A and B viruses. Because DPF2
plays a crucial role in the noncanonical NF-kappaB pathway, which negatively
regulates type I interferon (IFN) induction, we examined the relationship between
DPF2 and IFN responses during viral infection. The results showed that knockdown
of DPF2 resulted in increased expression of IFN-beta and induced phosphorylation
of STAT1 in infected cells. In addition, high levels of several
cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral
proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we
identified a novel host factor, DPF2, that is required for influenza virus to
evade the host immune response and that may serve as a potential antiviral
target.IMPORTANCE Influenza virus is responsible for seasonal epidemics and
occasional pandemics and is an ongoing threat to public health worldwide.
Influenza virus relies heavily on cellular factors to complete its life cycle.
Here we identified a novel host factor, DPF2, which is involved in influenza
virus infection. Our results showed that DPF2 plays a crucial role in the
replication and propagation of influenza virus. DPF2 functions in the
noncanonical NF-kappaB pathway, which negatively regulates type I IFN induction.
Thus, we investigated the relationship between the IFN response and DPF2 in
influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN
beta induction and expression of cytokines/chemokines and antiviral proteins.
This study provides evidence that influenza virus utilizes DPF2 to escape host
innate immunity.
PMID- 28404847
TI - Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus
Fusion Protein Stabilized in a Noncleaved Prefusion Conformation.
AB - The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a
major target of the neutralizing antibody response to hRSV. This glycoprotein
undergoes a major structural shift from the prefusion (pre-F) to the postfusion
(post-F) state at the time of virus-host cell membrane fusion. Recent evidences
suggest that the pre-F state is a superior target for neutralizing antibodies
compared to the post-F state. Therefore, for vaccine purposes, we have designed
and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in
a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F
conformation, it was compared with a recombinant post-F molecule, called Post-F
XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational
stability different from that of Post-F-XC, as shown by chemical denaturation.
Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like
structure. In contrast, Post-F-XC had a typical elongated conical shape.
Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules
had common rigid folding core and dynamic regions and provided structural insight
for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was
shown to deplete hRSV-neutralizing antibodies from human serum more efficiently
than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly
potent monoclonal antibody specific for the pre-F conformation. In conclusion,
this construct presents several pre-F characteristics, does not switch to the
post-F conformation, and presents antigenic features required for a protective
neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a
promising candidate vaccine antigen.IMPORTANCE Human respiratory syncytial virus
(RSV) is a global leading cause of infant mortality and adult morbidity. The
development of a safe and efficacious RSV vaccine remains an important goal. The
RSV class I fusion (F) glycoprotein is considered one of the most promising
vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state
is a superior target for neutralizing antibodies. Our study presents the
physicochemical characterization of Pre-F-GCN4t, a molecule designed to be
stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F
GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F
conformation. Our results show that Pre-F-GCN4t presents characteristics of a
stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such
an antigen may represent a significant advance in the development of an RSV
vaccine.
PMID- 28404848
TI - Unique Structural Features of Influenza Virus H15 Hemagglutinin.
AB - Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2
hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were
isolated from humans during 2013. The isolation of avian H15 viruses is, however,
quite rare and, until recently, geographically restricted to wild shorebirds and
waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150
loop (loop beginning at position 150) of the receptor-binding site common to this
subgroup and a unique insertion in the 260-loop compared to any other subtype.
Here, we show that the H15 HA has a high preference for avian receptor analogs by
glycan array analyses. The H15 HA crystal structure reveals that it is
structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider
than all other HAs due to a tilt and opening of the HA1 subunits of the head
domain. The extended 150-loop of the H15 HA retains the conserved conformation as
in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA
surface and can contribute to antigenic variation in H15 HAs. Since avian-origin
H15 HA viruses have been shown to cause enhanced disease in mammalian models,
further characterization and immune surveillance of H15 viruses are
warranted.IMPORTANCE In the last 2 decades, an apparent increase has been
reported for cases of human infection by emerging avian influenza A virus
subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other
member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that
also include H7 and H10. H15 viruses have been restricted to Australia, but
recent isolation of H15 viruses in western Siberia suggests that they could be
spread more globally via the avian flyways that converge and emanate from this
region. Here we report on characterization of the three-dimensional structure and
receptor specificity of the H15 hemagglutinin, revealing distinct features and
specificities that can aid in global surveillance of such viruses for potential
spread and emerging threat to the human population.
PMID- 28404850
TI - Stress Hormones Epinephrine and Corticosterone Selectively Modulate Herpes
Simplex Virus 1 (HSV-1) and HSV-2 Productive Infections in Adult Sympathetic, but
Not Sensory, Neurons.
AB - Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect and establish latency in
peripheral neurons, from which they can reactivate to cause recurrent disease
throughout the life of the host. Stress is associated with the exacerbation of
clinical symptoms and the induction of recurrences in humans and animal models.
The viruses preferentially replicate and establish latency in different subtypes
of sensory neurons, as well as in neurons of the autonomic nervous system that
are highly responsive to stress hormones. To determine if stress-related hormones
modulate productive HSV-1 and HSV-2 infections within sensory and autonomic
neurons, we analyzed viral DNA and the production of viral progeny after
treatment of primary adult murine neuronal cultures with the stress hormones
epinephrine and corticosterone. Both sensory trigeminal ganglion (TG) and
sympathetic superior cervical ganglion (SCG) neurons expressed adrenergic
receptors (activated by epinephrine) and the glucocorticoid receptor (activated
by corticosterone). Productive HSV infection colocalized with these receptors in
SCG but not in TG neurons. In productively infected neuronal cultures,
epinephrine treatment significantly increased the levels of HSV-1 DNA replication
and production of viral progeny in SCG neurons, but no significant differences
were found in TG neurons. In contrast, corticosterone significantly decreased the
levels of HSV-2 DNA replication and production of viral progeny in SCG neurons
but not in TG neurons. Thus, the stress-related hormones epinephrine and
corticosterone selectively modulate acute HSV-1 and HSV-2 infections in
autonomic, but not sensory, neurons.IMPORTANCE Stress exacerbates acute disease
symptoms resulting from HSV-1 and HSV-2 infections and is associated with the
appearance of recurrent skin lesions in millions of people. Although stress
hormones are thought to impact HSV-1 and HSV-2 through immune system suppression,
sensory and autonomic neurons that become infected by HSV-1 and HSV-2 express
stress hormone receptors and are responsive to hormone fluctuations. Our results
show that autonomic neurons are more responsive to epinephrine and corticosterone
than are sensory neurons, demonstrating that the autonomic nervous system plays a
substantial role in HSV pathogenesis. Furthermore, these results suggest that
stress responses have the potential to differentially impact HSV-1 and HSV-2 so
as to produce divergent outcomes of infection.
PMID- 28404849
TI - Quantitative Proteomic Analysis of Mosquito C6/36 Cells Reveals Host Proteins
Involved in Zika Virus Infection.
AB - Zika virus (ZIKV) is an emerging arbovirus belonging to the genus Flavivirus of
the family Flaviviridae During replication processes, flavivirus manipulates host
cell systems to facilitate its replication, while the host cells activate
antiviral responses. Identification of host proteins involved in the flavivirus
replication process may lead to the discovery of antiviral targets. The
mosquitoes Aedes aegypti and Aedes albopictus are epidemiologically important
vectors for ZIKV, and effective restrictions of ZIKV replication in mosquitoes
will be vital in controlling the spread of virus. In this study, an iTRAQ-based
quantitative proteomic analysis of ZIKV-infected Aedes albopictus C6/36 cells was
performed to investigate host proteins involved in the ZIKV infection process. A
total of 3,544 host proteins were quantified, with 200 being differentially
regulated, among which CHCHD2 can be upregulated by ZIKV infection in both
mosquito C6/36 and human HeLa cells. Our further study indicated that CHCHD2 can
promote ZIKV replication and inhibit beta interferon (IFN-beta) production in
HeLa cells, suggesting that ZIKV infection may upregulate CHCHD2 to inhibit IFN-I
production and thus promote virus replication. Bioinformatics analysis of
regulated host proteins highlighted several ZIKV infection-regulated biological
processes. Further study indicated that the ubiquitin proteasome system (UPS)
plays roles in the ZIKV entry process and that an FDA-approved inhibitor of the
20S proteasome, bortezomib, can inhibit ZIKV infection in vivo Our study
illustrated how host cells respond to ZIKV infection and also provided a
candidate drug for the control of ZIKV infection in mosquitoes and treatment of
ZIKV infection in patients.IMPORTANCE ZIKV infection poses great threats to human
health, and there is no FDA-approved drug available for the treatment of ZIKV
infection. During replication, ZIKV manipulates host cell systems to facilitate
its replication, while host cells activate antiviral responses. Identification of
host proteins involved in the ZIKV replication process may lead to the discovery
of antiviral targets. In this study, the first quantitative proteomic analysis of
ZIKV-infected cells was performed to investigate host proteins involved in the
ZIKV replication process. Bioinformatics analysis highlighted several ZIKV
infection-regulated biological processes. Further study indicated that the
ubiquitin proteasome system (UPS) plays roles in the ZIKV entry process and that
an FDA-approved inhibitor of the UPS, bortezomib, can inhibit ZIKV infection in
vivo Our study not only illustrated how host cells respond to ZIKV infection but
also provided a candidate drug for the control of ZIKV infection in mosquitoes
and treatment of ZIKV infection in patients.
PMID- 28404851
TI - Membrane Penetration by Bacterial Viruses.
AB - The bacteriophage phi29 infects Gram-positive Bacillus subtilis with a short
noncontractile tail. Recent studies showed that the phi29 tail protein gp9 forms
a hexameric tube with six long loops of membrane-active peptides blocking in the
tube at the distal end of the tail. The long loops exit on genome release and
form a membrane pore for passage of the genome. The membrane penetration
mechanism of the phi29 tail might be common among tailed bacteriophages.
PMID- 28404852
TI - Attachment and Postattachment Receptors Important for Hepatitis C Virus Infection
and Cell-to-Cell Transmission.
AB - Hepatitis C virus (HCV) requires multiple receptors for its attachment to and
entry into cells. Our previous studies found that human syndecan-1 (SDC-1), SDC
2, and T cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) are
HCV attachment receptors. Other cell surface molecules, such as CD81, Claudin-1
(CLDN1), Occludin (OCLN), SR-BI, and low-density lipoprotein receptor (LDLR),
function mainly at postattachment steps and are considered postattachment
receptors. The underlying molecular mechanisms of different receptors in HCV cell
free and cell-to-cell transmission remain elusive. In the present study, we used
a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9
technology, gene-specific small interfering RNAs, and a newly developed
luciferase-based reporter system to quantitatively determine the importance of
individual receptors in HCV cell-free and cell-to-cell transmission. Knockouts of
SDC-1 and SDC-2 resulted in remarkable reductions of HCV infection and cell
attachment, whereas SDC-3 and SDC-4 knockouts did not affect HCV infection.
Defective HCV attachment to SDC-1 and/or SDC-2 knockout cells was completely
restored by SDC-1 and SDC-2 but not SDC-4 expression. Knockout of the attachment
receptors SDC-1, SDC-2, and TIM-1 also modestly decreased HCV cell-to-cell
transmission. In contrast, silencing and knockout of the postattachment receptors
CD81, CLDN1, OCLN, SR-BI, and LDLR greatly impaired both HCV cell-free and cell
to-cell transmission. Additionally, apolipoprotein E was found to be important
for HCV cell-to-cell spread, but very-low-density lipoprotein (VLDL)-containing
mouse serum did not affect HCV cell-to-cell transmission, although it inhibited
cell-free infection. These findings demonstrate that attachment receptors are
essential for initial HCV binding and that postattachment receptors are important
for both HCV cell-free and cell-to-cell transmission.IMPORTANCE The importance
and underlying molecular mechanisms of cell surface receptors in HCV cell-free
and cell-to-cell transmission are poorly understood. The role of some of the HCV
attachment and postattachment receptors in HCV infection and cell-to-cell spread
remains controversial. Using CRISPR-Cas9-mediated knockouts of specific cellular
genes, we demonstrate that both SDC-1 and SDC-2, but not SDC-3 or SDC-4, are bona
fide HCV attachment receptors. We also used a newly developed luciferase-based
reporter system to quantitatively determine the importance of attachment and
postattachment receptors in HCV cell-to-cell transmission. SDC-1, SDC-2, TIM-1,
and SR-BI were found to modestly promote HCV cell-to-cell spread. CD81, CLDN1,
OCLN, and LDLR play more important roles in HCV cell-to-cell transmission.
Likewise, apolipoprotein E (apoE) is critically important for HCV cell-to-cell
spread, unlike VLDL-containing mouse serum, which did not affect HCV cell-to-cell
spread. These findings suggest that the mechanism(s) of HCV cell-to-cell spread
differs from that of cell-free infection.
PMID- 28404854
TI - Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during
Rebound Simian/Human Immunodeficiency Virus Viremia.
AB - Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune
response that impacts the plasma viral load set point and the rate of progression
to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to
undetectable levels that rebound upon cART treatment interruption. Following cART
withdrawal, the memory component of the virus-specific adaptive immune response
may improve viral control compared to primary infection. Here, using primary
infection and treatment interruption data from macaques infected with
simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load
but an unchanged viral set point during viral rebound. The addition of an
autologous stem cell transplant before cART withdrawal alters viral dynamics: we
found a higher rebound set point but similar peak viral loads compared to the
primary infection. Mathematical modeling of the data that accounts for
fundamental immune parameters achieves excellent fit to heterogeneous viral
loads. Analysis of model output suggests that the rapid memory immune response
following treatment interruption does not ultimately lead to better viral
containment. Transplantation decreases the durability of the adaptive immune
response following cART withdrawal and viral rebound. Our model's results
highlight the impact of the endogenous adaptive immune response during primary
SHIV infection. Moreover, because we capture adaptive immune memory and the
impact of transplantation, this model will provide insight into further studies
of cure strategies inspired by the Berlin patient.IMPORTANCE HIV patients who
interrupt combination antiretroviral therapy (cART) eventually experience viral
rebound, the return of viral loads to pretreatment levels. However, the "Berlin
patient" remained free of HIV rebound over a decade after stopping cART. His cure
is attributed to leukemia treatment that included an HIV-resistant stem cell
transplant. Inspired by this case, we studied the impact of stem cell
transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic
mathematical model, we found that while primary infection generates an adaptive
immune memory response, stem cell transplantation disrupts this learned immunity.
The results have implications for HIV cure regimens based on stem cell
transplantation.
PMID- 28404856
TI - A dose-dependent plasma signature of the safety and immunogenicity of the rVSV
Ebola vaccine in Europe and Africa.
AB - The 2014-2015 Ebola epidemic affected several African countries, claiming more
than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective
vaccines could prevent or limit future outbreaks. The recombinant vesicular
stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked
immunogenicity and efficacy in humans but is reactogenic at higher doses. To
understand its effects, we examined plasma samples from 115 healthy volunteers
from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo.
Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to
3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2,
MIP-1beta/CCL4, IL-6, TNF-alpha, IL-1Ra, and IL-10 occurred on day 1. A signature
explaining 68% of cytokine/chemokine vaccine-response variability was identified.
Its score was higher in HD versus LD vaccinees and was associated positively with
vaccine viremia and negatively with cytopenia. It was higher in vaccinees with
injection-site pain, fever, myalgia, chills, and headache; higher scores
reflected increasing severity. In contrast, HD vaccinees who subsequently
developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose
did not influence the signature despite its influence on specific outcomes. The
Geneva-derived signature associated strongly (rho = 0.97) with that of a cohort
of 75 vaccinees from a parallel trial in Lambarene, Gabon. Its score in Geneva HD
vaccinees with subsequent arthritis was significantly lower than that in
Lambarene HD vaccinees, none of whom experienced arthritis. This signature, which
reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across
doses and continents, should prove useful in assessments of other vaccines.
PMID- 28404853
TI - Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the
Eye.
AB - As its name suggests, the host receptor herpesvirus entry mediator (HVEM)
facilitates herpes simplex virus (HSV) entry through interactions with a viral
envelope glycoprotein. HVEM also bridges several signaling networks, binding
ligands from both tumor necrosis factor (TNF) and immunoglobulin (Ig)
superfamilies with diverse, and often opposing, outcomes. While HVEM was first
identified as a viral entry receptor for HSV, it is only recently that HVEM has
emerged as an important host factor in immunopathogenesis of ocular HSV type 1
(HSV-1) infection. Surprisingly, HVEM exacerbates disease development in the eye
independently of entry. HVEM signaling has been shown to play a variety of roles
in modulating immune responses to HSV and other pathogens, and there is
increasing evidence that these effects are responsible for HVEM-mediated
pathogenesis in the eye. Here, we review the dual branches of HVEM function
during HSV infection: entry and immunomodulation. HVEM is broadly expressed;
intersects two important immunologic signaling networks; and impacts
autoimmunity, infection, and inflammation. We hope that by understanding the
complex range of effects mediated by this receptor, we can offer insights
applicable to a wide variety of disease states.
PMID- 28404857
TI - Opening borders for foreign bodies.
AB - Targeting macrophage-specific receptors involved in host immune response against
foreign bodies eliminates the fibrotic processes responsible for failure of many
implantable biomedical devices.
PMID- 28404855
TI - Genome-Wide Screening Uncovers the Significance of N-Sulfation of Heparan Sulfate
as a Host Cell Factor for Chikungunya Virus Infection.
AB - The molecular mechanisms underlying chikungunya virus (CHIKV) infection are
poorly characterized. In this study, we analyzed the host factors involved in
CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which
an exon-trapping vector was introduced, were challenged with a vesicular
stomatitis virus pseudotype bearing the CHIKV E3 to E1 envelope proteins.
Analysis of genes enriched in the cells resistant to the pseudotyped virus
infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the
infectivity of the clinically isolated CHIKV Thai#16856 strain to HAP1 cells.
Knockout of NDST1 that catalyzes N-sulfation of HS greatly decreased the binding
and infectivity of CHIKV Thai#16856 strain but not infectivity of Japanese
encephalitis virus (JEV) and yellow fever virus (YFV). While glycosaminoglycans
were commonly required for the efficient infectivity of CHIKV, JEV, and YFV, as
shown by using B3GAT3 knockout cells, the tropism for N-sulfate was specific to
CHIKV. Expression of chondroitin sulfate (CS) in NDST1-knockout HAP1 cells did
not restore the binding of CHIKV Thai#16856 strain and the infectivity of its
pseudotype but restored the infectivity of authentic CHIKV Thai#16856, suggesting
that CS functions at later steps after CHIKV binding. Among the genes enriched in
this screening, we found that TM9SF2 is critical for N-sulfation of HS and
therefore for CHIKV infection because it is involved in the proper localization
and stability of NDST1. Determination of the significance of and the relevant
proteins to N-sulfation of HS may contribute to understanding mechanisms of CHIKV
propagation, cell tropism, and pathogenesis.IMPORTANCE Recent outbreaks of
chikungunya fever have increased its clinical importance. Chikungunya virus
(CHIKV) utilizes host glycosaminoglycans to bind efficiently to its target cells.
However, the substructure in glycosaminoglycans required for CHIKV infection have
not been characterized. Here, we unveil that N-sulfate in heparan sulfate is
essential for the efficient infection of a clinical CHIKV strain to HAP1 cells
and that chondroitin sulfate does not help the CHIKV binding but does play roles
at the later steps in HAP1 cells. We show, by comparing previous reports using
Chinese hamster ovary cells, along with another observation that enhanced
infectivity of CHIKV bearing Arg82 in envelope E2 does not depend on
glycosaminoglycans in HAP1 cells, that the infection manner of CHIKV varies among
host cells. We also show that TM9SF2 is required for CHIKV infection to HAP1
cells because it is involved in the N-sulfation of heparan sulfate through
ensuring NDST1 activity.
PMID- 28404858
TI - Small spice for big wounds: Can curcumin close the gap?
AB - Nanoformulation of curcumin may be the key to unlocking its wound healing
potential.
PMID- 28404859
TI - Fiber to the rescue?
AB - Fiber supplementation reduces the proinflammatory effects of high-fat, high
calorie meal consumption.
PMID- 28404860
TI - Vitamin C puts the pedal to the metal.
AB - Increased iron in cancer cells drives selective sensitization of tumors to
ascorbate treatment to prolong survival.
PMID- 28404861
TI - Erratum for the Research Article: "Integrated molecular analysis of tumor
biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and
resistance" by W. Roh, P.-L. Chen, A. Reuben, C. N. Spencer, P. A. Prieto, J. P.
Miller, V. Gopalakrishnan, F. Wang, Z. A. Cooper, S. M. Reddy, C. Gumbs, L.
Little, Q. Chang, W.-S.Chen, K. Wani, M. P. De Macedo, E. Chen, J. L. Austin
Breneman, H. Jiang, J. Roszik, M. T. Tetzlaff, M. A. Davies, J. E. Gershenwald,
H. Tawbi, A. J. Lazar, P. Hwu, W.-J. Hwu, A. Diab, I. C. Glitza, S. P. Patel, S.
E. Woodman, R. N. Amaria, V. G. Prieto, J. Hu, P. Sharma, J. P. Allison, L. Chin,
J. Zhang, J. A. Wargo, P. A. Futreal.
PMID- 28404862
TI - Engagement of the medical-technology sector with society.
AB - The medical-technology sector must educate society in an unbiased rational way
about the successes and benefits of biotechnology innovation.
PMID- 28404863
TI - Individuals with progranulin haploinsufficiency exhibit features of neuronal
ceroid lipofuscinosis.
AB - Heterozygous mutations in the GRN gene lead to progranulin (PGRN)
haploinsufficiency and cause frontotemporal dementia (FTD), a neurodegenerative
syndrome of older adults. Homozygous GRN mutations, on the other hand, lead to
complete PGRN loss and cause neuronal ceroid lipofuscinosis (NCL), a lysosomal
storage disease usually seen in children. Given that the predominant clinical and
pathological features of FTD and NCL are distinct, it is controversial whether
the disease mechanisms associated with complete and partial PGRN loss are similar
or distinct. We show that PGRN haploinsufficiency leads to NCL-like features in
humans, some occurring before dementia onset. Noninvasive retinal imaging
revealed preclinical retinal lipofuscinosis in heterozygous GRN mutation
carriers. Increased lipofuscinosis and intracellular NCL-like storage material
also occurred in postmortem cortex of heterozygous GRN mutation carriers.
Lymphoblasts from heterozygous GRN mutation carriers accumulated prominent NCL
like storage material, which could be rescued by normalizing PGRN expression.
Fibroblasts from heterozygous GRN mutation carriers showed impaired lysosomal
protease activity. Our findings indicate that progranulin haploinsufficiency
caused accumulation of NCL-like storage material and early retinal abnormalities
in humans and implicate lysosomal dysfunction as a central disease process in GRN
associated FTD and GRN-associated NCL.
PMID- 28404864
TI - Longitudinal peripheral blood transcriptional analysis of a patient with severe
Ebola virus disease.
AB - The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra
Leone was unprecedented in the number of documented cases, but there have been
few published reports on immune responses in clinical cases and their
relationships with the course of illness and severity of Ebola virus disease.
Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia,
fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although
experimental treatments are in development, there are no current U.S. Food and
Drug Administration-approved vaccines or therapies. We report a detailed study of
host gene expression as measured by microarray in daily peripheral blood samples
collected from a patient with severe Ebola virus disease. This individual was
provided with supportive care without experimental therapies at the National
Institutes of Health Clinical Center from before onset of critical illness to
recovery. Pearson analysis of daily gene expression signatures revealed marked
gene expression changes in peripheral blood leukocytes that correlated with
changes in serum and peripheral blood leukocytes, viral load, antibody responses,
coagulopathy, multiple organ dysfunction, and then recovery. This study revealed
marked shifts in immune and antiviral responses that preceded changes in medical
condition, indicating that clearance of replicating Ebola virus from peripheral
blood leukocytes is likely important for systemic viral clearance.
PMID- 28404865
TI - Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is
enhanced by PD-1 checkpoint blockade.
AB - Pathological angiogenesis is a hallmark of cancer and a therapeutic target.
Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also
known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and
limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a
bispecific antibody (A2V) provided superior therapeutic benefits, as compared to
the single agents, in both genetically engineered and transplant tumor models,
including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor
(RIP1-Tag2), and melanoma. Mechanistically, A2V promoted vascular regression,
tumor necrosis, and antigen presentation by intratumoral phagocytes. A2V also
normalized the remaining blood vessels and facilitated the extravasation and
perivascular accumulation of activated, interferon-gamma (IFNgamma)-expressing
CD8+ cytotoxic T lymphocytes (CTLs). Whereas the antitumoral activity of A2V was,
at least partly, CTL-dependent, perivascular T cells concurrently up-regulated
the expression of the immune checkpoint ligand programmed cell death ligand 1 (PD
L1) in tumor endothelial cells. IFNgamma neutralization blunted this adaptive
response, and PD-1 blockade improved tumor control by A2V in different cancer
models. These findings position immune cells as key effectors of antiangiogenic
therapy and support the rationale for cotargeting angiogenesis and immune
checkpoints in cancer therapy.
PMID- 28404867
TI - Dynamic cellular finite-element method for modelling large-scale cell migration
and proliferation under the control of mechanical and biochemical cues: a study
of re-epithelialization.
AB - Computational modelling of cells can reveal insight into the mechanisms of the
important processes of tissue development. However, current cell models have
limitations and are challenged to model detailed changes in cellular shapes and
physical mechanics when thousands of migrating and interacting cells need to be
modelled. Here we describe a novel dynamic cellular finite-element model
(DyCelFEM), which accounts for changes in cellular shapes and mechanics. It also
models the full range of cell motion, from movements of individual cells to
collective cell migrations. The transmission of mechanical forces regulated by
intercellular adhesions and their ruptures are also accounted for. Intra-cellular
protein signalling networks controlling cell behaviours are embedded in
individual cells. We employ DyCelFEM to examine specific effects of biochemical
and mechanical cues in regulating cell migration and proliferation, and in
controlling tissue patterning using a simplified re-epithelialization model of
wound tissue. Our results suggest that biochemical cues are better at guiding
cell migration with improved directionality and persistence, while mechanical
cues are better at coordinating collective cell migration. Overall, DyCelFEM can
be used to study developmental processes when a large population of migrating
cells under mechanical and biochemical controls experience complex changes in
cell shapes and mechanics.
PMID- 28404868
TI - Collective benefits in traffic during mega events via the use of information
technologies.
AB - Information technologies today can inform each of us about the route with the
shortest time, but they do not contain incentives to manage travellers such that
we all get collective benefits in travel times. To that end we need travel demand
estimates and target strategies to reduce the traffic volume from the congested
roads during peak hours in a feasible way. During large events, the traffic
inconveniences in large cities are unusually high, yet temporary, and the entire
population may be more willing to adopt collective recommendations for collective
benefits in traffic. In this paper, we integrate, for the first time, big data
resources to estimate the impact of events on traffic and propose target
strategies for collective good at the urban scale. In the context of the Olympic
Games in Rio de Janeiro, we first predict the expected increase in traffic. To
that end, we integrate data from mobile phones, Airbnb, Waze and transit
information, with game schedules and expected attendance in each venue. Next, we
evaluate different route choice scenarios for drivers during the peak hours.
Finally, we gather information on the trips that contribute the most to the
global congestion which could be redirected from vehicles to transit.
Interestingly, we show that (i) following new route alternatives during the event
with individual shortest times can save more collective travel time than keeping
the routine routes used before the event, uncovering the positive value of
information technologies during events; (ii) with only a small proportion of
people selected from specific areas switching from driving to public transport,
the collective travel time can be reduced to a great extent. Results are
presented online for evaluation by the public and policymakers (www.flows
rio2016.com (last accessed 3 September 2017)).
PMID- 28404866
TI - Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through
HEV formation.
AB - Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular
endothelial growth factor receptor 2) are commonly used in the clinic, but their
beneficial effects are only observed in a subset of patients and limited by
induction of diverse relapse mechanisms. We describe the up-regulation of an
adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1
(programmed cell death ligand 1), the ligand of the negative immune checkpoint
regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-gamma
expressing T cells in distinct intratumoral cell types in refractory pancreatic,
breast, and brain tumor mouse models. Successful treatment with a combination of
anti-VEGFR2 and anti-PD-L1 antibodies induced high endothelial venules (HEVs) in
PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2
pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs
promoted lymphocyte infiltration and activity through activation of lymphotoxin
beta receptor (LTbetaR) signaling. Further activation of LTbetaR signaling in
tumor vessels using an agonistic antibody enhanced HEV formation, immunity, and
subsequent apoptosis and necrosis in pancreatic and mammary tumors. Finally,
LTbetaR agonists induced HEVs in recalcitrant GBM, enhanced cytotoxic T cell
(CTL) activity, and thereby sensitized tumors to antiangiogenic/anti-PD-L1
therapy. Together, our preclinical studies provide evidence that anti-PD-L1
therapy can sensitize tumors to antiangiogenic therapy and prolong its efficacy,
and conversely, antiangiogenic therapy can improve anti-PD-L1 treatment
specifically when it generates intratumoral HEVs that facilitate enhanced CTL
infiltration, activity, and tumor cell destruction.
PMID- 28404869
TI - Histology-based homogenization analysis of soft tissue: application to prostate
cancer.
AB - It is well known that the changes in tissue microstructure associated with
certain pathophysiological conditions can influence its mechanical properties.
Quantitatively relating the tissue microstructure to the macroscopic mechanical
properties could lead to significant improvements in clinical diagnosis,
especially when the mechanical properties of the tissue are used as diagnostic
indices such as in digital rectal examination and elastography. In this study, a
novel method of imposing periodic boundary conditions in non-periodic finite
element meshes is presented. This method is used to develop quantitative
relationships between tissue microstructure and its apparent mechanical
properties for benign and malignant tissue at various length scales. Finally, the
inter-patient variation in the tissue properties is also investigated. Results
show significant changes in the statistical distribution of the mechanical
properties at different length scales. More importantly the loss of the normal
differentiation of glandular structure of cancerous tissue has been demonstrated
to lead to changes in mechanical properties and anisotropy. The proposed
methodology is not limited to a particular tissue or material and the example
used could help better understand how changes in the tissue microstructure caused
by pathological conditions influence the mechanical properties, ultimately
leading to more sensitive and accurate diagnostic technologies.
PMID- 28404870
TI - Enhancing regenerative approaches with nanoparticles.
AB - In this review, we discuss recent developments in the field of nanoparticles and
their use in tissue regeneration approaches. Owing to their unique chemical
properties and flexibility in design, nanoparticles can be used as drug delivery
systems, to create novel features within materials or as bioimaging agents, or
indeed these properties can be combined to create smart multifunctional
structures. This review aims to provide an overview of this research field where
the focus will be on nanoparticle-based strategies to stimulate bone
regeneration; however, the same principles can be applied for other tissue and
organ regeneration strategies. In the first section, nanoparticle-based methods
for the delivery of drugs, growth factors and genetic material to promote tissue
regeneration are discussed. The second section deals with the addition of
nanoparticles to materials to create nanocomposites. Such materials can improve
several material properties, including mechanical stability, biocompatibility and
biological activity. The third section will deal with the emergence of a
relatively new field of research using nanoparticles in advanced cell imaging and
stem cell tracking approaches. As the development of nanoparticles continues,
incorporation of this technology in the field of regenerative medicine will
ultimately lead to new tools that can diagnose, track and stimulate the growth of
new tissues and organs.
PMID- 28404871
TI - On the biomechanical analysis of the calories expended in a straight boxing jab.
AB - Boxing and related sports activities have become a standard workout regime at
many fitness studios worldwide. Oftentimes, people are interested in the calories
expended during these workouts. This note focuses on determining the calories in
a boxer's jab, using kinematic vector-loop relations and basic work-energy
principles. Numerical simulations are undertaken to illustrate the basic model.
Multi-limb extensions of the model are also discussed.
PMID- 28404872
TI - Synthetic associative learning in engineered multicellular consortia.
AB - Associative learning (AL) is one of the key mechanisms displayed by living
organisms in order to adapt to their changing environments. It was recognized
early as a general trait of complex multicellular organisms but is also found in
'simpler' ones. It has also been explored within synthetic biology using
molecular circuits that are directly inspired in neural network models of
conditioning. These designs involve complex wiring diagrams to be implemented
within one single cell, and the presence of diverse molecular wires become a
challenge that might be very difficult to overcome. Here we present three
alternative circuit designs based on two-cell microbial consortia able to
properly display AL responses to two classes of stimuli and displaying long- and
short-term memory (i.e. the association can be lost with time). These designs
might be a helpful approach for engineering the human gut microbiome or even
synthetic organoids, defining a new class of decision-making biological circuits
capable of memory and adaptation to changing conditions. The potential
implications and extensions are outlined.
PMID- 28404873
TI - Sulfhydration-associated phosphodiesterase 5A dimerization mediates vasorelaxant
effect of hydrogen sulfide.
AB - The study was designed to examine if the vasorelaxant effect of hydrogen sulfide
was mediated by sulfhydration-associated phosphodiesterase (PDE) 5A dimerization.
The thoracic aorta of rat was separated and the vasorelaxant effects were
examined with in vitro vascular perfusion experiments. The dimerization and
sulfhydration of PDE 5A and soluble guanylatecyclase (sGC) were measured. PDE 5A
and protein kinase G (PKG) activities were tested. Intracellular cGMP content was
detected by enzyme-linked immunosorbent assay (ELISA). The results showed that
NaHS relaxed isolated rat vessel rings at an EC50 of (1.79 +/- 0.31)*10-5mol/L,
associated with significantly increased PKG activity and cGMP content in vascular
tissues. Sulfhydration of sGC beta1 was increased, while the levels of sGC
alphabeta1 dimers were apparently decreased after incubation with NaHS in
vascular tissues. Moreover, PDE 5A homodimers were markedly decreased, and
accordingly the PDE 5A activity demonstrated by the content of 5'-GMP was
significantly decreased after incubation with NaHS or GYY4137. Mechanistically,
both NaHS and GYY4137 significantly enhanced the PDE 5A sulfhydration in vascular
tissues. DTT partially abolished the effects of NaHS on PDE 5A activity, cGMP
content and vasorelaxation. Therefore, the present study for the first time
suggested that H2S exerted vasorelaxant effect probably via sulfhydration
associated PDE 5A dimerization.
PMID- 28404874
TI - Identification of JL1037 as a novel, specific, reversible lysine-specific
demethylase 1 inhibitor that induce apoptosis and autophagy of AML cells.
AB - Lysine-specific demethylase 1 (LSD1) has been recognized as a potential
therapeutic target for acute myeloid leukemia (AML). Herein, we identified a
novel LSD1 inhibitor, JL1037, via Computer Aided Drug Design technology. JL1037
is a potent, selective and reversible LSD1 inhibitor with IC50s of 0.1 MUM and
>1.5 MUM for LSD1 and monoamine oxidases A/B (MAO-A/B), respectively. Treatment
of THP-1 and Kasumi-1 cell lines with JL1037 resulted in dose dependent
accumulation of H3K4me1 and H3K4me2, the major substrates of LSD1, as well as
inhibition of cell proliferation, blockade of cell cycle and induction of
apoptosis. Further investigations demonstrated that JL1037 could upregulate cell
cycle-related proteins P21, P57, pro-apoptotic protein Bax and downregulate anti
apoptosis proteins Bcl-2 and Bcl-XL. JL1037 appeared to activate autophage
response in AML cell lines as well as primary cells from AML patients by
increasing LC3-II expression and the formation of autophagosomes and
autolysosomes in cytoplasm. Co-treatment with autophagy inhibitor chloroquine
(CQ) enhanced JL1037-induced cell apoptosis. Moreover, daily intravenous
administration of JL1037 tended to reduce tumor burden and prolong the survival
of t(8;21) leukemia mice. In conclusion, JL1037 exhibited potent anti-leukemia
effect and could be a potential therapeutic agent for AML treatment.
PMID- 28404875
TI - Fhit, a tumor suppressor protein, induces autophagy via 14-3-3tau in non-small
cell lung cancer cells.
AB - Inactivation of the fragile histidine triad (Fhit) gene has been reported in the
majority of human cancers, particularly in lung cancer. The role of Fhit as a
tumor suppressor gene has been well documented, and restoration of Fhit
expression suppresses tumorigenicity in tumor cell lines and in mouse models by
inducing apoptosis and inhibiting proliferation of tumor cells. Autophagy is a
catabolic pathway, whereby cytoplasmic proteins and organelles are sequestered in
vacuoles and delivered to lysosomes for degradation and recycling. Although
autophagy is necessary for cell survival under stress conditions, recent studies
have shown that autophagy can also promote cell death. Due to the fact that both
autophagy induction and Fhit expression are commonly associated with nutrient
starvation, we hypothesized that Fhit expression may be related to autophagy
induction. In the present study, we assessed whether Fhit overexpression by gene
transfer induces autophagy in Fhit-deficient non-small cell lung cancer (NSCLC)
cells. The results of our study indicate that Fhit protein induces autophagy in
NSCLC cells, and that this autophagy prevents apoptotic cell death in vivo and in
vitro in a 14-3-3tau protein-dependent manner. To the best of our knowledge, this
is the first report to describe Fhit-induced autophagy. Suppressing autophagy
might be a promising therapeutic option to enhance the efficacy of Fhit gene
therapy in NSCLC.
PMID- 28404877
TI - Clinical study of the time of repeated computed tomography and replanning for
patients with nasopharyngeal carcinoma.
AB - PURPOSE: To study the necessity of repeat computed tomography (CT) scan and
replanning and know a more accurate time using weekly kilovoltage cone beam
computed tomography (kV-CBCT) scans for patients with nasopharyngeal carcinoma
(NPC) during radiotherapy. METHODS AND MATERIALS: Thirteen NPC patients treated
with IMRT were enrolled into this prospective study. Weekly pretreatment kV-CBCT
scans were performed on the 1st, 6th, 11st, 16th, 21st and 26th radiation time,
respectively. Target delineations were contoured on all fractionated CBCT images,
including the gross tumor volume of the primary nasopharyngeal tumor (GTVnx) and
parotid glands. The volumes of GTVnx and parotid glands were calculated
automatically using the Pinnacle3 8.0 system. Compared to the original GTVnx, the
percentage of shrinking volume (DeltaP) >= 50% was considered significantly.
RESULTS: As the radiation proceeding, the GTVnx had a trend of shrinkage. Of all
13 patients, 11 cases (84.6%) had the volume shrinking >= 50% before the 21st
radiation and 12 cases (92.3%) before the 26th radiation. And the parotid volume
decreased significantly in the first four-week radiation, 6.45 +/- 3.16cm3
(range, 3.06-13.9cm3) for the left parotid gland and 5.78 +/- 2.39cm3 (range,
2.70-11.2cm3) for the right. Furthermore, only a little displacement occurred to
bilateral parotid glands. CONCLUSION: The replanning for NPC patients with IMRT
is necessary, and the time between the 21st to 25th radiations is appropriate.
PMID- 28404876
TI - Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA,
MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated
immune recognition.
AB - Acute myeloid leukemia (AML) is a disease with great morphological and genetic
heterogeneity, which complicates its prognosis and treatment. The hypomethylating
agents azacitidine (Vidaza(r), AZA) and decitabine (Dacogen(r), DAC) have been
approved for the treatment of AML patients, but their mechanisms of action are
poorly understood. Natural killer (NK) cells play an important role in the
recognition of AML blasts through the interaction of the activating NKG2D
receptor with its ligands (NKG2DL: MICA/B and ULBPs1-3). However, soluble NKG2DL
(sNKG2DL) can be released from the cell surface, impairing immune recognition.
Here, we examined whether hypomethylating agents modulate the release of sNKG2DL
from AML cells. Results demonstrated that AZA- and DAC-treated AML cells reduce
the release of sNKG2DL, preventing downregulation of NKG2D receptor on the cell
surface and promoting immune recognition mediated by NKG2D-NKG2DL engagement. We
show that the shedding of MICA, MICB and ULBP2 is inhibited by the increased
expression of TIMP3, an ADAM17 inhibitor, after DAC treatment. The TIMP3 gene is
highly methylated in AML cells lines and in AML patients (25.5%), in which it is
significantly associated with an adverse cytogenetic prognosis of the disease.
Overall, TIMP3 could be a target of the demethylating treatments in AML patients,
leading to a decrease in MICA, MICB and ULBP2 shedding and the enhancement of the
lytic activity of NK cells through the immune recognition mediated by the NKG2D
receptor.
PMID- 28404878
TI - Activation of liver X receptor delayed the retinal degeneration of rd1 mice
through modulation of the immunological function of glia.
AB - Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited
eye disease characterized by progressive degeneration of photoreceptors.
Recently, immune cells, including microglia, Muller cells and astrocytes, in
degenerative retina are demonstrated to play key roles in the development of RD
and can be used as potential therapeutic targets. Liver X receptors (LXRs) are
important immuno-inflammatory response transcription factors that have been
reported to be a new potential therapeutic drug target for neurodegenerative
diseases. However, the potential therapeutic utility of LXRs for RP has not been
evaluated. In the present study, Pde6beta (rd1) mice received intraperitoneal
injections of T0901317 (T0, 50 mg/kg/d) or vehicle (2% DMSO) for 7 days with age
matched C57/BL6 mice as controls. The effect of T0 was examined by quantitating
photoreceptor apoptosis, microglial density and the expression of inflammatory
mediators; the underlying mechanisms were then explored with a microarray assay.
T0 markedly delayed apoptosis of the photoreceptors, partially through
suppressing the activation of microglia and the gliosis of Muller cells, and
decreased the expression levels of IL-6, iNOS, COX-2 and ENG in rd1 mice; as a
result, the visual function of T0-treated rd1 mice measured with
electroretinograms (ERG) was preserved for a longer time than that of vehicle
treated rd1 mice. The microarray assay showed that the Janus kinase/Signal
Transducer and Activator of Transcription (JAK-STAT) signaling pathway was
significantly affected in the retina of rd1 mice with T0 treatment. Our data
suggested that T0 modulated the immunologic function of glia cells in the
degenerative retina through the JAK3/STAT pathway and delayed the apoptosis of
photoreceptors.
PMID- 28404879
TI - Developmental transcriptome profiling of bovine muscle tissue reveals an abundant
GosB that regulates myoblast proliferation and apoptosis.
AB - The formation of bovine skeletal muscle involves complex developmental and
physiological processes that play a vital role in determining the quality of
beef; however, the regulatory mechanisms underlying differences in meat quality
are largely unknown. We conducted transcriptome analysis of bovine muscle tissues
to compare gene expression profiles between embryonic and adult stages. Total
RNAs from skeletal muscle of Qinchuan cattle at fetal and adult stages were used
to construct libraries for Illumina next-generation sequencing using the Ribo
Zero RNA sequencing (RNA-Seq) method. We found a total of 19,695 genes to be
expressed in fetal and adult stages, whereby 3,299 were expressed only in fetal,
and 433 only in adult tissues. We characterized the role of a candidate gene
(GosB), which was highly (but differentially) expressed in embryonic and adult
skeletal muscle tissue. GosB increased the number of myoblasts in the S-phase of
the cell cycle, and decreased the proportion of cells in the G0/G1 phase. GosB
promoted the proliferation of myoblasts and protected them from apoptosis via
regulating Bcl-2 expression and controlling the intracellular calcium
concentration. Modulation of GosB expression in muscle tissue may emerge as a
potential target in breeding strategies attempting to alter myoblast numbers in
cattle.
PMID- 28404880
TI - Serotonergic system antagonists target breast tumor initiating cells and
synergize with chemotherapy to shrink human breast tumor xenografts.
AB - Breast tumors comprise an infrequent tumor cell population, termed breast tumor
initiating cells (BTIC), which sustain tumor growth, seed metastases and resist
cytotoxic therapies. Hence therapies are needed to target BTIC to provide more
durable breast cancer remissions than are currently achieved. We previously
reported that serotonergic system antagonists abrogated the activity of mouse
BTIC resident in the mammary tumors of a HER2-overexpressing model of breast
cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT)
biosynthesis and activity, including US Federal Food and Drug Administration
(FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor
cell lines regardless of their clinical or molecular subtype. Notably, inhibitors
of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non
neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT
receptors compromised BTIC activity as assessed by functional sphere-forming
assays. Consistent with these findings, human breast tumor cells express TPH1, 5
HT and SERT independent of their molecular or clinical subtype. Exposure of
breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake
inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug
treated tumor cells into immune-compromised mice. Moreover, another SSRI
(vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor
xenografts in immune-compromised mice by inhibiting tumor cell proliferation and
inducing their apoptosis. Collectively our data suggest that antidepressants in
combination with cytotoxic anticancer therapies may be an appropriate treatment
regimen for testing in clinical trials.
PMID- 28404881
TI - Tanshinone IIA attenuates renal damage in STZ-induced diabetic rats via
inhibiting oxidative stress and inflammation.
AB - Oxidative stress and inflammation have been demonstrated to be involved in the
onset and promotion of diabetic nephropathy (DN).Tanshinone IIA (Tan) possesses
both antioxidant and anti-inflammatory properties. Here, the aim of the present
study was to explore whether Tan could attenuate renal damage in the rats with
streptozotocin (STZ)-induced diabetes and its potential mechanisms. Tan was
gavaged to STZ-induced diabetic rats at the dose of 10mg/kg once a day for 12
weeks. Tan treatment significantly attenuated albuminuria and renal
histopathology in diabetic rats. Besides, Tan treatment also effectively
inhibited oxidative stress and inflammatory reaction in the kidneys of diabetic
rats. Our study provided evidence that the protective effect of Tan on diabetes
induced renal injury is associated with inhibition of oxidative stress and
inflammation. Tan may be a potential candidate for the treatment of DN.
PMID- 28404882
TI - Prototheca zopfii isolated from bovine mastitis induced oxidative stress and
apoptosis in bovine mammary epithelial cells.
AB - Bovine protothecal mastitis results in considerable economic losses worldwide.
However, Prototheca zopfii induced morphological alterations and oxidative stress
in bovine mammary epithelial cells (bMECs) is not comprehensively studied yet.
Therefore, the aim of this current study was to investigate the P. zopfii induced
pathomorphological changes, oxidative stress and apoptosis in bMECs. Oxidative
stress was assessed by evaluating catalase (CAT), superoxide dismutase (SOD),
glutathione peroxidase (GPx), malondialdehyde (MDA) contents and lactate
dehydrogenase (LDH) activity, while ROS generation and apoptosis was measured by
confocal laser scanning microscopy. The results revealed that infection of P.
zopfii genotype II (GTII) significantly changed bMECs morphology, increased
apoptotic rate and MDA contents at 12 h (p < 0.05) and 24 h (p < 0.01) in
comparison with control group, in time-dependent manner. LDH activity and ROS
generation was also increased (p < 0.01) at 12 h and 24 h. However, SOD and CAT
contents in bMECs infected with GTII were decreased (p < 0.05) at 12 h, while GPx
(p < 0.01), SOD (p < 0.05) and CAT (p < 0.01) levels were reduced at 24 h. In
case of GTI, only CAT and GPx activities were significantly decreased when the
duration prolonged to 24 h but lesser than GTII. This suggested that GTII has
more devastating pathogenic effects in bMECs, and the findings of this study
concluded that GTII induced apoptosis and oxidative stress in bMECs via the
imbalance of oxidant and antioxidant defenses as well as the production of
intracellular ROS.
PMID- 28404883
TI - miR-29a regulates the proliferation and differentiation of retinal progenitors by
targeting Rbm8a.
AB - During development, tight regulation of the expansion of retinal progenitor cells
(RPCs) and their differentiation into neuronal and glial cells is important for
retinal formation and function. Our study demonstrated that microRNA (miR)-29a
modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one
of the factors in the exon junction complex). Particularly, overexpression of miR
29a reduced RPC proliferation but accelerated RPC differentiation. By contrast,
reduction of endogenous miR-29a elicited the opposite effects. Overexpression of
miR-29a repressed the translation of Rbm8a, thus negatively regulating RPC
proliferation and promoting the neuronal and glial differentiation of RPCs, and
knockdown of endogenous Rbm8a phenocopied the observed effects of miR-29a
overexpression. Furthermore, a luciferase reporter assay showed that miR-29a
directly interacted with the Rbm8a mRNA 3'UTR, which indicated that Rbm8a is the
direct target of miR-29a. To further verify the result, co-overexpression of the
Rbm8a 3' UTR-wt (plasmids into which the Rbm8a 3' UTR sequence had been
introduced) and miR-29a in RPCs rescued the phenotype associated with miR-29a
overexpression, reversing the promotion of differentiation and inhibition of
proliferation. These results show a novel mechanism by which miR-29a regulates
the proliferation and differentiation of RPCs through Rbm8a.
PMID- 28404884
TI - DFNA5 promoter methylation a marker for breast tumorigenesis.
AB - BACKGROUND: Identification of methylation markers that are sensitive and specific
for breast cancer may improve early detection. We hypothesize that DFNA5 promoter
methylation can be a valuable epigenetic biomarker, based upon strong indications
for its role as tumor suppressor gene and its function in regulated cell death.
RESULTS: Statistically different levels of methylation were seen, with always
very low levels in healthy breast reduction samples, very high levels in part of
the adenocarcinoma samples and slightly increased levels in part of the normal
tissue samples adjacent the tumor. One of the CpGs (CpG4) showed the best
differentiation. A ROC curve for DFNA5 CpG4 methylation showed a sensitivity of
61.8% for the detection of breast cancer with a specificity of 100%. MATERIALS
AND METHODS: We performed methylation analysis on four CpGs in the DFNA5 promoter
region by bisulfite pyrosequencing on 123 primary breast adenocarcinomas and 24
healthy breast reductions. For 16 primary tumors, corresponding histological
normal tissue adjacent to the tumor was available. CONCLUSIONS: We conclude that
DFNA5 methylation shows strong potential as a biomarker for detection of breast
cancer. Slightly increased methylation in histologically normal breast tissue
surrounding the tumor suggests that it may be a good early detection marker.
PMID- 28404885
TI - Significant association between lncRNA H19 polymorphisms and cancer
susceptibility: a meta-analysis.
AB - Previous epidemiological research suggests polymorphisms in long non-coding RNA
(lncRNA) H19 are associated with an increased risk of cancer, but the results are
inconsistent. We therefore conducted a meta-analysis to more accurately determine
the association between lncRNA H19 polymorphisms and cancer risk. The PubMed,
Embase, and Science Citation Index online databases were searched and 11 relevant
studies involving a total of 33,209 participants were identified. Odds ratios
(ORs) and corresponding 95% confidence interval (CIs) from these studies were
used to detect associations between H19 polymorphisms and cancer risk using five
genetic models. The pooled result suggested that the rs2839698 G>A polymorphism
was associated with digestive cancer risk in all five models. Moreover, a
protective effect against cancer development was observed for the T allele
variant of the rs2107425 C>T polymorphism, especially in Caucasian patient
populations. No significant associations were found between lncRNA H19 rs217727
G>A polymorphism and cancer risk. In summary, the rs2839698 G>A and rs2107425 C>T
polymorphisms in lncRNA H19 may therefore play opposing roles during cancer
development, and their effects may vary depending on cancer type and patient
ethnicity.
PMID- 28404886
TI - Cytokine-induced killer cells/dendritic cells-cytokine induced killer cells
immunotherapy combined with chemotherapy for treatment of colorectal cancer in
China: a meta-analysis of 29 trials involving 2,610 patients.
AB - PURPOSE: To systematically evaluate the efficacy and safety of Cytokine-induced
killer cells/dendritic cells-cytokine induced killer cells (CIK/DC-CIK)
immunotherapy in treating advanced colorectal cancer (CRC) patients. RESULTS: 29
trials including 2,610 CRC patients were evolved. Compared with chemotherapy
alone, the combination of chemotherapy with CIK/DC-CIK immunotherapy
significantly prolonged the overall survival rate (OS) and disease-free survival
rate (DFS) (1-5 year OS, P < 0.01; 1-, 2-, 3- and 5-year DFS, P < 0.01). The
combined therapy also improved patients' overall response, disease control rate
and life quality (P < 0.05). After immunotherapy, lymphocyte subsets percentages
of CD3+, CD3-CD56+, CD3+CD56+ and CD16+CD56+ (P < 0.01) and cytokines levels of
IL-2 and IFN-gamma (P < 0.05) were increased, while CD4+, CD8+ and CD4+CD25+ and
IL-6 and TNF-alpha did not show significant change (P > 0.05). MATERIALS AND
METHODS: Clinical trials reporting response or safety of CIK/DC-CIK immunotherapy
treating advanced CRC patients and published before September 2016 were searched
in Cochrane Library, EMBASE, PubMed, Wanfang and CNKI database. Research quality
and heterogeneity were evaluated before analysis. Pooled analyses were performed
using random or fixed-effect models. CONCLUSIONS: The combination of CIK/DC-CIK
immunotherapy and chemotherapy prolong CRC patients' survival time, enhanced
patients' immune function and alleviates the adverse effects caused by
chemotherapy.
PMID- 28404887
TI - The mutation of Trp64Arg in beta3-adrenoreceptor-encoding gene is significantly
associated with increased hypertension risk and elevated blood pressure: a meta
analysis.
AB - This meta-analysis was implemented to test the association of a missense
mutation, Trp64Arg, in beta3-adrenoreceptor-encoding gene (ADRB3) with both
hypertension risk and blood pressure (BP) changes. A systematic search of three
publicly-available databases was launched to look for articles published as of
December 2016. Qualification appraisal and data extraction were independently
done by two researchers. Pooled estimates were expressed as odds ratio (OR) or
weighted mean difference (WMD), and their 95% confidence intervals (95% CIs).
There were separately 21 (3750/4225 patients/controls) and 17 (6100 subjects)
individual studies for hypertension risk and BP changes. Integral analyses
revealed that Trp64Arg mutation was associated with the significantly increased
risk of hypertension, and particularly, the 64Trp/64Arg heterozygote carriers
were 1.23-times more likely to develop hypertension compared with the 64Trp/64Trp
homozygote carriers (OR = 1.23, 95% CI: 1.02~1.46, P = 0.021). Publication bias
was extremely low for all integral comparisons. In stratified analyses,
significance was spotted in populations of Chinese descent, in retrospective
studies, in hospital-based studies, in age-matched case-control studies, in
studies enrolling patients with mean body mass index < 25 kg/m2 and in studies
with total sample size >= 240. Heterogeneity was improved for most stratified
comparisons. Further in hypertensive patients, the 64Trp/64Arg heterozygote
carriers had significantly higher systolic (WMD = 0.87 mmHg, 95% CI: 0.39~1.35, P
< 0.001) and diastolic (WMD = 0.88 mmHg, 95% CI: 0.59~1.17, P < 0.001) BP than
64Trp/64Trp homozygote carriers. Altogether, ADRB3 gene Trp64Arg mutation was
significantly associated with an increased predisposition toward hypertension and
elevated systolic/diastolic BP in hypertensive patients, suggesting that Trp64Arg
is an important hypertension-susceptibility marker.
PMID- 28404888
TI - Ecto-5'-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem
like cells.
AB - Identification of a specific biomarker for cancer stem cells (CSCs) is of
potential applications in the development of effective therapeutic strategies for
renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and
surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as
spheroids in serum-free medium supplemented with mitogens. This subpopulation
possessed key characteristics defining CSCs. We also identified that surgically
removed ccRCC tissues were heterogenic and there was a subpopulation of cells
that was highly stained with rhodamine-123. Based on membrane-proteomic analyses,
CD73 was identified as a candidate biomarker. We further found that CD73high
cells were highly tumorigenic. As few as 100 CD73high cells were capable of
forming xenograft tumors in non obese diabetic/severe combined immunodeficiency
disease mice, whereas 1 * 105 CD73low cells did not initiate tumor formation.
During successive culture, the CD73high population regenerated both CD73high and
CD73low cells, whereas the CD73low population remained low expression level of
CD73. Furthermore, the CD73high cells were more resistant to radiation and DNA
damaging agents than the CD73low cells, and expressed a panel of 'stemness' genes
at a higher level than the CD73low cells. These findings suggest that a high
level of CD73 expression is a bona fide biomarker of ccRCC stem-like cells.
Future research will aim at the elucidation of the underlying mechanisms of CD73
in RCC development and the distinct aspects of ccRCC stem-like cells from other
tumor types.
PMID- 28404889
TI - Cryptic BCR-ABL fusion gene as variant rearrangement in chronic myeloid leukemia:
molecular cytogenetic characterization and influence on TKIs therapy.
AB - At diagnosis, about 5% of Chronic Myeloid Leukemia (CML) patients lacks
Philadelphia chromosome (Ph), despite the presence of the BCR/ABL rearrangement.
Two mechanisms have been proposed about the occurrence of this rearrangement: the
first one is a cryptic insertion between chromosomes 9 and 22; the second one
involves two sequential translocations: a classic t(9;22) followed by a reverse
translocation, which reconstitutes the normal morphology of the partner
chromosomes. Out of 398 newly diagnosed CML patients, we selected 12 Ph-negative
cases. Six Ph-negative patients treated with tyrosine kinase inhibitors (TKIs)
were characterized, in order to study the mechanisms leading to the rearrangement
and the eventual correlation with prognosis in treatment with TKIs. FISH analysis
revealed cryptic insertion in 5 patients and classic translocation in the last
one. In more detail, we observed 4 different patterns of rearrangement,
suggesting high genetic heterogeneity of these patients. In our cases, the
BCR/ABL rearrangement mapped more frequently on 9q34 region than on 22q11 region,
in contrast to previous reports. Four patients, with low Sokal risk, achieved
Complete Cytogenetic Response and/or Major Molecular Response after TKIs therapy.
Therapy resistance was observed in one patient with duplication of BCR/ABL
rearrangement and in another one with high risk. Even if the number patient is
inevitably low, we can confirm that the rare Ph-negative CML patients do not
constitute a "warning" category, meanwhile the presence of further cytogenetic
abnormalities remains an adverse prognostic factor even in TKI era.
PMID- 28404891
TI - HMGB1 promotes differentiation syndrome by inducing hyperinflammation via MEK/ERK
signaling in acute promyelocytic leukemia cells.
AB - Differentiation therapy based on all-trans-retinoic acid (ATRA) and arsenic
trioxide (ATO) for the treatment of acute promyelocytic leukemia (APL) is
complicated by the development of differentiation syndrome (DS), which can be
fatal. We examined the role of HMGB1 (high-mobility group box 1) in DS using both
in vitro and in vivo models. HMGB1 and the pro-inflammatory cytokines IL-1beta
and TNF-alpha were gradually released from NB4 and HL-60 cells treated with ATRA
and/or ATO. Similarly, higher serum HMGB1 levels positively correlated with the
clinical status of DS patients. Exogenous HMGB1 promoted rapid release of IL
1beta and TNF-alpha as well as elevated expression of ICAM-1, without altering
cell differentiation. Exogenous HMGB1 also enhanced pulmonary infiltration and up
regulated ICAM-1 expression in the ATRA-treated DS mouse. Pharmacological
inhibition or depletion of MEK1/2 reduced the cytokine levels and suppressed
expression of ICAM-1 and the adhesion of HMGB1-treated NB4 cells to endothelial
cells, implicating MEK/ERK signaling in the response to HMGB1 during DS.
Treatment with a HMGB1-neutralizing antibody reduced secretion of TNF-alpha and
IL-1beta, arrested the elevation of ICAM-1 and blunted the activation of ERK1/2
in ATRA-induced NB4 cells. The HMGB1-neutralizing antibody also decreased ICAM-1
expression and reduced mortality in ATRA-treated DS model mice. These findings
demonstrate that released HMGB1 is central to DS, and that targeting HMGB1 may be
of therapeutic value in the treatment of DS.
PMID- 28404892
TI - Gambogic acid suppresses cancer invasion and migration by inhibiting TGFbeta1
induced epithelial-to-mesenchymal transition.
AB - The epithelial-to-mesenchymal transition (EMT) contributes to the disruption of
cell-cell junctions and imbues cancer cells with invasive and migratory
properties. In this study, we investigated the effect of gambogic acid, a
xanthone extracted from the resin of Garciania hanburyi, on transforming growth
factor beta1 (TGFbeta1)-induced EMT. Gambogic acid inhibited the invasion and
migration of TGFbeta1-induced A549 cells in vitro. Gambogic acid also increased
the mRNA and protein expression of E-cadherin, but repressed the mRNA and protein
expression of N-cadherin, vimentin, and transcription factor TWIST1. Further
examination of the mechanism revealed that the nuclear factor kappaB (NF-kappaB)
pathway is involved in this regulation of EMT-related biomarkers. Gambogic acid
inhibited NF-kappaB p65 nuclear translocation and the phosphorylation of the
inhibitor of NF-kappaB (IkappaBalpha) and IkappaBalpha kinase (IKKalpha).
Gambogic acid also suppressed the EMT induced by TGFbeta1 and tumor necrosis
factor alpha by inhibiting the NF-kappaB pathway. Our data also indicate that
gambogic acid inhibited the primary lesion and lung metastasis of orthotopic
model of A549 cells in vivo. We propose that gambogic acid might be developed as
a candidate drug with therapeutic potential for the treatment of cancer invasion
and migration.
PMID- 28404893
TI - A varying-coefficient cox model for the effect of CA19-9 kinetics on overall
survival in patients with advanced pancreatic cancer.
AB - PURPOSE: To evaluate the relationship between serum CA19-9 and overall survival
in patients with advanced pancreatic cancer. METHODS: 109 advanced pancreatic
cancer patients with gemcitabine based first-line chemotherapy were included. The
effect of pretreatment CA19-9 level on overall survival was modeled by Cox
proportional hazard regression. The effect of CA19-9 kinetics on overall survival
was modeled by an extended Cox regression with a time varying coefficient and a
time varying covariate. RESULTS: Univariate analysis indicated that baseline CA19
9 correlated with OS (HR = 1.66, p < 0.01) and this association remained
significant within multivariate analysis (HR = 1.56, P < 0.01). For the analysis
of CA19-9 kinetics, the extended Cox model showed that the effect of CA19-9 on
overall survival changed with time: increased in the first two months and reached
the top at a HR of about 2, then decreased for the next two months to a HR of
about 1.56 and finally tended to be stable. The combination of pretreatment CA19
9 and CA19-9 at 2 month may better evaluate the patients' prognosis compared to
pretreatment CA19-9 alone. CONCLUSION: Pretreatment CA19-9 and CA19-9 kinetics
may serve as a useful serum biomarker in advanced pancreatic cancer.
PMID- 28404894
TI - Induction and characterization of anti-tumor endothelium immunity elicited by
ValloVax therapeutic cancer vaccine.
AB - ValloVax is a placental endothelium derived vaccine which induces tissue
nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate
mechanisms of action, we showed that production of ValloVax, which involves
treating placental endothelial cells with IFN-gamma, results in upregulation of
HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction,
ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from
ValloVax immunized mice was capable of killing in vitro tumor-like endothelium
but not control endothelium. Using defined antigens associated with tumor
endothelial cells, specific molecular entities were identified as being targeted
by ValloVax induced antibodies. Binding of predominantly IgG antibodies to
ValloVax cells was confirmed by flow cytometry. Further suggesting direct killing
of tumor endothelial cells was expression of TUNEL positive cells, as well as,
reduction in tumor oxygenation. Supporting a role for antibody mediated
responses, cell depletion experiments suggested a predominant role of B cells in
maintaining an intact anti-tumor endothelial response. Adoptive transfer
experiments suggested that infusion of CD3+ T cells from immunized mice was
sufficient to transfer tumor protection. Generation of memory T cells selective
to tumor endothelial specific markers was observed. Functional confirmation of
memory responses was observed in tumor rechallenge experiments. Furthermore, we
observed that both PD-1 or CTLA-4 blockade augmented antitumor effects of
ValloVax. These data suggest a T cell induced B cell mediated anti-tumor
endothelial response and set the framework clinical trials through elucidation of
mechanism of action.
PMID- 28404895
TI - Expression of BRCA1 and ERCC1 as predictive clinical outcome after
radiochemotherapy in patients with locoregionally moderate-advanced
nasopharyngeal carcinoma.
AB - In this study, we examined ERCC1 and BRCA1 expression and clinical outcome of 201
phase-III-IV nasopharyngeal carcinoma patients who were treated with cisplatin
based induced chemotherapy and concurrent radiochemotherapy. The chemotherapy
response rate of BRCA1- and BRCA1+ patients was 73.6% and 55.8%, respectively. In
addition, the chemotherapy response rate of ERCC1- and ERCC1+ patients was 76.9%
and 56.6%, respectively. In patients' tissues, ERCC1 expression associated with
BRCA1 expression. The chemotherapy response rate of BRCA1- and ERCC1- patients
was (82.1%) and higher than that of other groups (range 52.4-73.1%). The
radiochemotherapy response rate of BRCA1- and ERCC1- patients was higher than
that BRCA1+ and ERCC1+ patients. BRCA1- and ERCC1- patients showed higher 3-year
overall survival, failure-free survival, locoregional failure-free survival and
distant failure-free survival compared to BRCA1+ or ERCC1+ patients. Moreover,
the 3-year overall survival, failure-free survival and distant failure-free
survival of the BRCA1- and ERCC1- group were higher than that of other groups.
TNM stage, ERCC1 expression and the correlation between BRCA1 and ERCC1
expression seemed significant overall survival factors. In conclusion, in
nasopharyngeal carcinoma patients, ERCC1 and BRCA1 may be a predictor of response
to platinum-based chemotherapy and concurrent radiochemotherapy.
PMID- 28404896
TI - Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells
using the novel modular chimeric antigen receptor platform technology "UniCAR".
AB - New treatment options especially of solid tumors including for metastasized
prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with
chimeric antigen receptors (CARs) underline their impressive therapeutic
potential. However CARs currently applied in the clinics cannot be repeatedly
turned on and off potentially leading to severe life threatening side effects. To
overcome these problems, we recently described a modular CAR technology termed
UniCAR: UniCAR T cells are inert but can be turned on by application of one or
multiple target modules (TMs). Here we present preclinical data summarizing the
retargeting of UniCAR T cells to PCa cells using TMs directed to prostate stem
cell- (PSCA) or/and prostate specific membrane antigen (PSMA). In the presence of
the respective TM(s), we see a highly efficient target-specific and target
dependent activation of UniCAR T cells, secretion of pro-inflammatory cytokines,
and PCa cell lysis both in vitro and experimental mice.
PMID- 28404897
TI - TCF7L2 polymorphisms and the risk of schizophrenia in the Chinese Han population.
AB - Single nucleotide polymorphisms (SNPs) in TCF7L2 (Transcription Factor 7-Like 2)
reportedly affect susceptibility to schizophrenia (SCZ). We examined the
association between TCF7L2 polymorphisms and SCZ susceptibility in a Chinese Han
population. Six SNPs were genotyped in 499 SCZ patients and 500 healthy
individuals, after which their associations with SCZ were evaluated using the Chi
squared test and genetic model analyses. We observed that the allele A of
rs12573128 is associated with an increased SCZ risk (odds ratio [OR] = 1.33, 95%
confidence interval [CI]: 1.08-1.63, P = 0.006, adjusted P = 0.030). The AA
genotype of rs12573128 was associated with a higher SCZ risk than the GG
genotype, before and after adjustment for sex and age (adjusted OR = 2.97, 95%
CI: 1.49-5.92, P = 0.002). In addition, SNP rs12573128 was associated with 1.47
fold, 2.64-fold and 1.50-fold increases in SCZ risk of in dominant, recessive and
additive model, respectively (adjusted OR = 1.47, 95% CI = 1.09-1.99, P = 0.012;
Bonferroni adjusted P = 0.030). adjusted OR = 2.64, 95% CI = 1.34-5.18, P = 0.005
and adjusted OR = 1.50, 95% CI = 1.17-1.93, P = 0.002, respectively). These
results suggest rs12573128 is significantly associated with an increased risk of
SCZ in the Chinese Han population.
PMID- 28404898
TI - NUSAP1 promotes invasion and metastasis of prostate cancer.
AB - We have previously identified nucleolar and spindle associated protein 1 (NUSAP1)
as a prognostic biomarker in early stage prostate cancer. To better understand
the role of NUSAP1 in prostate cancer progression, we tested the effects of
increased and decreased NUSAP1 expression in cell lines, in vivo models, and
patient samples. NUSAP1 promotes invasion, migration, and metastasis, possibly by
modulating family with sequence similarity 101 member B (FAM101B), a transforming
growth factor beta 1 (TGFbeta1) signaling effector involved in the epithelial to
mesenchymal transition. Our findings provide insights into the importance of
NUSAP1 in prostate cancer progression and provide a rationale for further study
of NUSAP1 function, regulation, and clinical utility.
PMID- 28404899
TI - BALB/c mice immunized with a combination of virus-like particles incorporating
Kaposi sarcoma-associated herpesvirus (KSHV) envelope glycoproteins gpK8.1, gB,
and gH/gL induced comparable serum neutralizing antibody activity to UV
inactivated KSHV.
AB - Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is estimated to
account for over 44,000 new cases of Kaposi sarcoma annually, with 84% occurring
in Africa, where the virus is endemic. To date, there is no prophylactic vaccine
against KSHV. KSHV gpK8.1, gB, and gH/gL glycoproteins, implicated in the virus
entry into host cells, are attractive vaccine targets for eliciting potent
neutralizing antibodies (nAbs) against virus infection. We incorporated gpK8.1,
gB, or gH/gL on the surface of virus-like particles (VLPs) and characterized
these VLPs for their composition, size, and functionality. To determine which
viral glycoprotein(s) elicit the most effective serum-nAbs, we immunized BALB/c
mice with gpK8.1, gB, or gH/gL VLPs individually or in combination. Neutralizing
antibody assay revealed that sera from mice immunized with the VLPs inhibited
KSHV infection of HEK-293 cells in a dose-dependent manner. As a single
immunogen, gpK8.1 VLPs stimulated comparable nAb activity to that of UV
inactivated KSHV (UV-KSHV). In contrast, UV-KSHV stimulated higher titers of nAb
compared to gB (p = 0.0316) or gH/gL (p = 0.0486). Mice immunized with the
combination of gB and gH/gL VLPs had a better nAb response than those immunized
with either gB (p = 0.0268), or gH/gL (p = 0.0397) as single VLP immunogens.
Immunization with any VLP combination stimulated comparable nAb activity to UV
KSHV serum. Our data provide the first evidence that KSHV gpK8.1, gB, and gH/gL
glycoproteins can be incorporated onto the surface of VLPs and used as
prophylactic vaccine candidates, with potential to prevent KSHV infection.
PMID- 28404900
TI - 18F-deoxyglucose positron emission tomography/computed tomography to predict
local failure in esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma (ESCC) patients are at risk for local failure
(LF) following treatment. Predicting tumor regions at high risk for local failure
before radiotherapy may increase treatment efficacy by permitting an escalated
radiation dose specifically to those regions critical for tumor control. Forty
one patients with non-resectable locally advanced ESCC underwent 18F-deoxyglucose
positron emission tomography/computed tomography (FDG PET/CT) imaging before
concurrent chemoradiotherapy (CCRT). After CCRT, a second (failure) FDG PET/CT
was performed in cases of relapse. Failure FDG PET/CT scans were fused to pre
treatment scans to identify tumor regions at high risk for LF. Within a median
follow-up time of 26 months, 20 patients (48.8%) had LF. In 19 patients, the
failure occurred within a pre-treatment high FDG uptake region; the failure
occurred outside these regions in only one patient. Pre-treatment metabolic tumor
volume (MTV) was independently associated with LF (P<0.001, HR 1.128, 95% CI:
1.061-1.198). LF was more likely in patients with MTVs >=27 cm3. In initial
PET/CT images, when 50% maximum standardized uptake value (SUVmax) was used as
the threshold, delineated subvolumes overlapped LF regions. These results confirm
that LF occurs most commonly within pre-treatment high FDG uptake regions.
PMID- 28404901
TI - Long non-coding RNA TUG1 promotes endometrial cancer development via inhibiting
miR-299 and miR-34a-5p.
AB - It is generally known that the human genome makes a large amount of noncoding
RNAs compared with coding genes. Long non-coding RNAs (lncRNAs) which composed of
more than 200 nucleotides have been described as the largest subclass of the non
coding transcriptome in human noncoding RNAs. Existing research shows that
lncRNAs exerted biological functions in various tumors via participating in both
oncogenic and tumor suppressing pathways. The previous studies indicated that
lncRNA taurine upregulated 1 (TUG1) play important roles in the initiation and
progression of malignancies. In this study,based on previous research, we
investigated the expression and biological role of the lncRNA-TUG1. We analyzed
the relationship between lncRNA-TUG1and endometrial carcinoma (EC) in a total 104
EC carcinoma specimens, compared with that in normal tissues. We found that
lncRNA-TUG1 expression in cancer tissues was significantly higher than that in
adjacent tissues. Through a series of experiments, the results demonstrated that
lncRNA-TUG1 enhances the evolution and progression of EC through inhibiting miR
299 and miR-34a-5p.
PMID- 28404902
TI - Mechanism of modulation through PI3K-AKT pathway about Nepeta cataria L.'s
extract in non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) is regarded as one of the major intractable
diseases, which was cured mainly by chemotherapeutics in the clinical treatment
at present. But it is still a vital mission for the current medical and
researchers that hunting a natural medicine which have little side effects and
high-efficiency against the NSCLC on account of the shortcomings on current
drugs. Nepeta cataria L. plays an important role in anti-cancer treatment
according to the reports which was recorded in the Chinese Pharmacopoeia of
version 2015 and belongs to one of the Traditional Chinese medicine (TCM).
Microfluidic chip technology is widely used in scientific research field due to
its high-throughput, high sensitivity and low cost with the continuous progress
of science and technology. In this study, we investigate the effect of total
flavonoid extracted from Nepeta cataria L. (TFS) through human lung cancer cell
line A549 based on the microfluidic device and Flow Cytometry. So we detected the
mRNA expression of MicroRNA-126 (miR-126), VEGF, PI3K, PTEN and proteins
expression respectively to explore the partial PI3K-AKT pathway molecular
mechanisms through Quantitative Real-time PCR (qRT-PCR) and Western Blot. The
results showed that TFS can disturb the expression of miR-126 and regulate the
PI3K-AKT signaling pathway to meet the effect of anti-cancer. Taking all these
results into consideration we can draw a conclusion that TFS may be used as a
novel therapeutic agent for NSCLC in the near future.
PMID- 28404903
TI - Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular
interpretation of an old biomarker in gastric cancer.
AB - BACKGROUND: Gastric Cancer is one of the most lethal malignancies worldwide.
Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular
glutathione homeostasis. We aim to explore the clinical value of GGT in gastric
cancer. RESULTS: Among 322 patients enrolled, 65/82 patients were determined as
GGT positive in serum/tumor, respectively. High tumor GGT expression is
significantly associated with lymph node metastasis, histological subtype, and
Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have
shorter overall survival (P log-rank=0.001) and progress-free survival (P log
rank =0.001). Patients with both high tumor and serum GGT have the poorest
prognosis. The multivariable Cox analysis shows that the hazard ratio of overall
survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor
prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47).
These findings were further validated in six online datasets. Gene Sets
Enrichment Analysis showed that GGT promotes cancer progression through EMT,
KRAS, SRC and PKCA pathways. METHODS: Tumor GGT and serum GGT levels were
evaluated with immuno-histochemistry staining and enzymatic assay, respectively.
Kaplan-Meier curve and Cox regression model were used to test the association
between GGT and gastric cancer prognosis. Independent datasets from Gene
Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the
findings and explore the potential mechanisms. CONCLUSION: Both tumor GGT and
serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor
and serum GGT levels require more intense treatment and follow-up.
PMID- 28404904
TI - lambda-Carrageenan improves the antitumor effect of dendritic cellbased vaccine.
AB - In this study, we investigated the effect of lambda-carrageenan on the maturation
and function of dendritic cells (DCs) and its adjuvant effect on DC-based
vaccine. We found that lambda-carrageenan dose-dependently decreased the
endocytosis of DCs, promoted DC maturation and increased cytokine production
through TLR4 mediated signaling pathway. lambda-carrageenan treatment also
enhanced the ability of DCs in the stimulating allogenic splenocyte
proliferation. In TC-1 tumor mouse model, HPV peptides pulsed lambda-carrageenan
DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group.
The frequencies of CD4+ and CD8+ T cells in spleens of tumor mice and their
activation status were significantly increased in HPV-CGN-DC group, but the
frequencies of natural regulatory T cells and CD11b+Gr-1+ cells were
significantly decreased. Further, HPV-CGN-DC induced strong CD8+ T cell
responses, which are negatively correlated with tumor volumes. The results
suggested that lambda-carrageenan promoted DC maturation through TLR4 signaling
pathway and could be used as the adjuvant in DC-based vaccines.
PMID- 28404905
TI - OSR1 is a novel epigenetic silenced tumor suppressor regulating invasion and
proliferation in renal cell carcinoma.
AB - Renal cell carcinoma (RCC) is one of the most malignant tumors in human. Here, we
found that odd-skipped related transcription factor 1 (OSR1) was downregulated in
769-P and 786-O cells due to promoter CpG methylation. OSR1 expression could be
restored by pharmacological demethylation treatment in silenced cell lines.
Knockdown of OSR1 in two normal expressed cell lines- A498 and ACHN promoted cell
invasion and cellular proliferation. RNA-Sequencing analysis showed that
expression profile of genes involved in multiple cancer-related pathways was
changed when OSR1 was downregulated. By quantitative real-time PCR, we confirmed
that depletion of OSR1 repressed the expression of several tumor suppresor genes
involved in p53 pathway, such as p53, p21, p27, p57 and RB in A498 and ACHN.
Moreover, knockdown of OSR1 suppressed the transcriptional activity of p53. Of
note, OSR1 depletion also led to increased expression of a few oncogenic genes.
We further evaluated the clinical significance of OSR1 in primary human RCC
specimens by immunohistochemical staining and found that OSR1 expression was
downregulated in primary RCC and negatively correlated with histological grade.
Thus, our data indicate that OSR1 is a novel tumor suppressor gene in RCC.
Downregulation of OSR1 might represent a potentially prognostic marker and
therapeutic target for RCC.
PMID- 28404906
TI - Interleukin-1beta rs1143627 polymorphism with susceptibility to periodontal
disease.
AB - Association between interleukin-1 beta (IL-1beta) rs1143627 polymorphism and
periodontal disease susceptibility was inconsistent; hence we performed this meta
analysis to explore the precise correlation between them. The degree of
association was appraised through calculating pooled odds ratio (OR) and its 95%
confidence interval (CI). The databases known as PubMed, Embase, and Chinese
National Knowledge Infrastructure were searched up to October 26, 2016. A total
of 8 eligible case-control studies were finally included, which involved 229
aggressive periodontitis patients, 382 chronic periodontitis patients, and 555
healthy controls. All the five genetic models revealed a non-significant
association between IL-1beta rs1143627 polymorphism and periodontal disease
susceptibility (TT vs. CC: OR = 1.22, 95% CI = 0.80-1.87; CT+TT vs. CC: OR =
0.66, 95% CI = 0.44-1.01; TT vs. CT + CC: OR = 1.19, 95% CI = 0.81-1.74; T vs. C:
OR = 0.92, 95% CI = 0.81-1.12; CT vs. CC: OR = 0.92, 95% CI = 0.69-1.23).
Sensitivity analyses indicated that the results were robust and the subgroup
analyses reached similar conclusions. IL-1beta rs1143627 polymorphism is not
related to periodontal disease susceptibility in the overall population based on
the current evidence, but further studies are required in more large scale sample
size with risk factor adjusted.
PMID- 28404907
TI - Investigation of three potential autoantibodies in Sjogren's syndrome and
associated MALT lymphoma.
AB - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease which might
progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of
pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been
frequently reported. In this study, four proteins including cofilin-1, alpha
enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be
over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry,
and the finding was verified by the microarray analysis and western blotting
results. We then developed enzyme-linked immunosorbent assays for autoantibodies
including anti-cofilin-1, anti-alpha-enolase and anti-RGI2 with good quantitative
ability. The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and
anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy
controls. The combination of these three antiantibodies yielded an "area under
the curve" (AUC) value of 0.94 with an 86% sensitivity and 93% specificity in
distinguishing patients with pSS from healthy controls, an AUC value of 0.99 with
a 95% sensitivity and 94% specificity in distinguishing patients with pSS/MALT
from healthy controls and an AUC value of 0.86 with a 75% sensitivity and 94%
specificity in distinguishing pSS/MALT patients from pSS patients. Collectively,
we have successfully identified a panel of potential autoantigens that are
progressively up-regulated during the development of pSS and its progression to
MALT lymphoma. The autoantibody biomarkers may be used to help diagnose pSS and
predict its progression to MALT lymphoma.
PMID- 28404908
TI - Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in
endometrial cancer cells.
AB - Endometrial Carcinoma (EMCA) is the most common gynecologic malignancy and the
fourth most common malignancy in women in the United States. Yes-associated
protein (YAP) is a potent transcription coactivator acting via binding to the
TEAD transcription factor, and plays a critical role in organ size regulation.
Verteporfin (VP), a benzoporphyrin derivative, was identified as an inhibitor of
YAP-TEAD interaction. We investigated the therapeutic efficacy and mechanism of
VP in EMCA. The efficacy of VP on cell viability, cytotoxicity and invasion was
assayed in EMCA cell lines. An organoid model system was also developed to test
the effect of VP on apoptotic markers in an in vitro model system. Treatment with
VP resulted in a decrease in cell viability, invasion and an increase in
cytotoxicity of EMCA cells. These effects occurred as early as 15 minutes
following treatment. Similarly, VP treatment versus vehicle control increased
apoptosis in human organoid model systems. Quantitative RT-PCR, cDNA based RTPCR
array analysis and western blotting were performed to investigate the mechanism
of VP action. The cytotoxic and anti-proliferative effects appeared to be
independent of its effect on YAP. Our results suggest that VP is a promising
chemotherapeutic agent for the treatment of endometrial cancer.
PMID- 28404909
TI - Impact of CCL4 gene polymorphisms and environmental factors on oral cancer
development and clinical characteristics.
AB - In Taiwan, oral cancer has causally been associated with environmental
carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein
with a key role in inflammation and immune-regulation, was implicated in
carcinogenesis by facilitating instability in the tumor environment. The purpose
of this study was to identify gene polymorphisms of CCL4 specific to patients
with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological
characteristics. A total of 2,053 participants, including 1192 healthy people and
861 patients with oral cancer, were recruited for this study. Three single
nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time
PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the
GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated
with oral-cancer susceptibility. In addition, TA haplotype significantly
decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4
polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold
greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers
without the betel-nut chewing habit. Finally, patients with oral cancer who had
A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an
advanced tumor size (> T2) (p=0.046), compared to those patients with AA
homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential
predictive significance in oral carcinogenesis. Gene-environment interactions of
CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121
may be a factor to predict the tumor size in OSCC patients.
PMID- 28404910
TI - Thalidezine, a novel AMPK activator, eliminates apoptosis-resistant cancer cells
through energy-mediated autophagic cell death.
AB - Cancers illustrating resistance towards apoptosis is one of the main factors
causing clinical failure of conventional chemotherapy. Innovative therapeutic
methods which can overcome the non-apoptotic phenotype are needed. The AMP
activated protein kinase (AMPK) is the central regulator of cellular energy
homeostasis, metabolism, and autophagy. Our previous study showed that the
identified natural AMPK activator is able to overcome apoptosis-resistant cancer
via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for
chemoresistant cancers. Here, we unravelled that the bisbenzylisoquinoline
alkaloid thalidezine is a novel direct AMPK activator by using biolayer
interferometry analysis and AMPK kinase assays. The quantification of autophagic
EGFP-LC3 puncta demonstrated that thalidezine increased autophagic flux in HeLa
cancer cells. In addition, metabolic stress assay confirmed that thalidezine
altered the energy status of our cellular model. Remarkably, thalidezine-induced
autophagic cell death in HeLa or apoptosis-resistant DLD-1 BAX-BAK DKO cancer
cells was abolished by addition of autophagy inhibitor (3-MA) and AMPK inhibitor
(compound C). The mechanistic role of autophagic cell death in resistant cancer
cells was further supported through the genetic removal of autophagic gene7
(Atg7). Overall, thalidezine is a novel AMPK activator which has great potential
to be further developed into a safe and effective intervention for apoptosis- or
multidrug-resistant cancers.
PMID- 28404911
TI - Flattened microvessel independently predicts poor prognosis of patients with non
small cell lung cancer.
AB - Angiogenesis plays an essential role in improving tumor progression, whereas, its
value in prognosis predicting remains controversial, especially in non-small cell
lung cancer (NSCLC). Most recently, microvessel pattern has been raised as a
novel prognosis factor. In this study, flattened microvessel, evaluated by tumor
microvessel aspect ratio (TMAR), was conducted as a prognostic factor in NSCLC
patients. A total of 100 patients with NSCLC were retrospectively reviewed.
Microvessel in tumor was visualized by immunochemistry staining and then TMAR was
determined. The prognostic role of TMAR was evaluated by univariate and
multivariate analysis. Most of intratumor microvessels were flattened with a
median TMAR of 3.65 (range, 2.43 - 6.28). Patients were stratified into high TMAR
group (TMAR >= 3.6) and low TMAR group (TMAR < 3.6). Compared with subpopulation
with low TMAR, high TMAR had significantly high risk of cancer-related death
(univariate analysis: HR = 5.06, 95% CI: 2.44-10.47, p<0.001; multivariate
analysis: HR = 4.53, 95% CI: 1.70-12.06, p=0.002).In conclusion, the results of
our study demonstrate that flattened microvessel in tumor tissue is a promising
prognosis predictor of NSCLC patients.
PMID- 28404912
TI - Expression of Rho GTPases family in melanoma cells and its influence on
cytoskeleton and migration.
AB - Rho GTPases family members influenced the filopodia, lamellipodia, stress fiber
and adhesion plaque of melanoma cells through regulating cytoskeleton
recombination. The role of Rho GTPases family in the migration and invasion of
melanoma and its molecular mechanism were explored. The morphological difference
between three types of melanoma cells (M14, A375 and MV3) and human melanocyte
(MC) was observed by the Hoffman microscope. Cells were stained by phalloidin
labeled by rhodamine. The differences between 4 types of cells in filopodia,
lamellipodia, stress fiber and adhesion plaque (microfilament is the main
constituent) were observed under the super-high resolution microscope. The
migration ability of 4 types of cells was detected by Transwell migration assay.
QPCR was used to detect the mRNA transcription level of Rho GTPases family. WB
was adopted to detect the expression of RhoD and DIAPH2 proteins. There were
significant differences in filopodia, lamellipodia, stress fiber and adhesion
plaque between MC and 3 types of melanoma cells (M14, A375 and MV3). MC did not
have stress fiber or adhesion plaque, while M14, A375 and MV3 had stress fiber
and adhesion plaque. All 4 types of cells had thin and short filopodia. MV3 had
fewer but thicker stress fibers than the latter two. Transwell migration test
indicated the followings: M14 and A375 had a similar high migration rate; the
migration rate of MV3 was slightly low; MC did not have the ability of
transmembrane migration. QPCR results of Rho GTPases family in 4 types of cells
showed the change corresponding to immunofluorescence. WB results showed that
RhoD was barely expressed in M14, A375 or MV3. DIAPH2, the downstream effector
molecule of RhoD, had the corresponding change. Rho GTPases influences the
migration and invasion of melanoma cells through regulating filopodia,
lamellipodia, stress fiber and adhesion plaque (microfilament is the main
constituent).
PMID- 28404913
TI - A novel role of CKIP-1 in promoting megakaryocytic differentiation.
AB - Casein kinase 2-interacting protein-1 (CKIP-1) is a known regulator of
cardiomyocytes and macrophage proliferation. In this study, we showed that CKIP-1
was involved in the process of megakaryocytic differentiation. During
megakaryocytic differentiation of K562 cells, CKIP-1 was dramatically upregulated
and this upregulation induced by PMA was mediated through downregulation of
transcription factor GATA-1. By transient transfection, oligonucleotide-directed
mutagenesis and chromatin immunoprecipitation assays, we identified the
transcriptional regulation of CKIP-1 by GATA-1. Overexpression of CKIP-1
initiated events of spontaneous megakaryocytic differentiation in K562 cells.
Conversely, knockdown of CKIP-1 in cell lines suppressed megakaryocytic
differentiation. Mechanistically, overexpression of CKIP-1 changed the expression
levels of transcription factors that have been shown to be critical in erythro
megakaryocytic differentiation such as Fli-1, c-Myb and c-Myc. In vivo analysis
confirmed that CKIP-1-/- mice had decreased number of CD41+ cells harvested from
bone marrow, and lower platelet levels when compared to wild-type littermates.
This is the first direct evidence suggesting that CKIP-1 is a novel regulator of
megakaryocytic differentiation.
PMID- 28404914
TI - The preclinical assessment of XL388, a mTOR kinase inhibitor, as a promising anti
renal cell carcinoma agent.
AB - XL388 is a mammalian target of rapamycin (mTOR) kinase inhibitor. We demonstrated
that XL388 inhibited survival and proliferation of renal cell carcinoma (RCC)
cell lines (786-0 and A549) and primary human RCC cells. XL388 activated caspase
dependent apoptosis in the RCC cells. XL388 blocked mTOR complex 1 (mTORC1) and
mTORC2 activation, and depleted hypoxia-inducible factor 1alpha (HIF1alpha) and
HIF-2alpha expression in RCC cells. Yet, XL388 was ineffective in RCC cells with
mTOR shRNA knockdown or kinase-dead mutation. Notably, XL388 was more efficient
than mTORC1 inhibitors (rapamycin, everolimus and temsirolimus) in killing RCC
cells. Further studies showed that activation of MEK-ERK might be a key
resistance factor of XL388. Pharmacological or shRNA-mediated inhibition of MEK
ERK pathway sensitized XL388-induced cytotoxicity in RCC cells. In vivo, oral
administration of XL388 inhibited in nude mice 786-0 RCC tumor growth, and its
anti-tumor activity was sensitized with co-administration of the MEK-ERK
inhibitor MEK162. Together, these results suggest that concurrent inhibition of
mTORC1/2 by XL388 may represent a fine strategy to inhibit RCC cells.
PMID- 28404915
TI - Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression
in esophageal squamous cell carcinoma.
AB - Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role
in regulating the immune response against cancer. This study investigated the
prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating
immune cells (TILs) in the tumor microenvironment in Chinese patients with
esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin
embedded ESCC samples from treatment-naive patients with ESCC after surgery or by
diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of
PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the
degree of TIL infiltration was evaluated by examining hematoxylin and eosin
stained (H&E) specimens. PD-L1+ as defined as >=1% of tumor cell membranes
showing >=1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+.
In the definitive treatment group (patients who received curative esophagectomy
or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a
significantly shorter DFS and OS. In the palliative chemotherapy group exhibited,
neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1
expression was positively associated with TIL density. In 17 paired tumor tissues
collected before and after treatment, an increase in PD-L1 expression was
associated with disease progression, whereas a decrease in PD-L1 expression was
associated with response to chemotherapy or disease control. So, PD-L1 expression
was associated with a significantly worse prognosis in patients with ESCC. These
observations suggest that PD-L1 may play a critical role in ESCC cancer
progression and provide a rationale for developing PD-L1 inhibitors for treatment
of a subset of ESCC patients.
PMID- 28404916
TI - Expression of HIF-1alpha in medullary thyroid cancer identifies a subgroup with
poor prognosis.
AB - BACKGROUND: Medullary thyroid cancer (MTC) comprises only 4% of all thyroid
cancers and originates from the parafollicular C-cells. HIF-1alpha expression has
been implied as an indicator of worse prognosis in various solid tumors. However,
whether expression of HIF-1alpha is a prognosticator in MTC remained unclear. Our
aim was to evaluate the prognostic value of HIF-1alpha in patients with MTC.
METHODS: All patients with MTC who were operated on between 1988 and 2014 in five
tertiary referral centers in The Netherlands were included. A tissue microarray
was constructed in which 111 primary tumors could be analyzed for expression of
HIF-1alpha, CAIX, Glut-1, VEGF and CD31 and correlated with clinicopathologic
variables and survival. RESULTS: The mean age of patients was 46.3 years (SD
15.6), 59 (53.2%) were male. Of the 111 primary tumors, 49 (44.1%) were HIF
1alpha negative and 62 (55.9%) were HIF-1alpha positive. Positive HIF-1alpha
expression was an independent negative indicator for progression free survival
(PFS) in multivariate cox regression analysis (HR 3.1; 95% CI 1.3 - 7.3). Five
years survival decreased from 94.0% to 65.9% for the HIF-1alpha positive group
(p=0.007). Even within the group of patients with TNM-stage IV disease, HIF
1alpha positivity was associated with a worse prognosis, shown by a decrease in 5
years survival of 88.0% to 49.3% (p=0.020). CONCLUSION: Expression of HIF-1alpha
is strongly correlated with adverse prognosis of MTC. This could open up new ways
for targeted systemic therapy of MTC.
PMID- 28404917
TI - Expression and functional regulation of stemness gene Lgr5 in esophageal squamous
cell carcinoma.
AB - Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated
cells with biological characteristics that include the capacity for self-renewal,
differentiation into various lineages, and tumor initiation. To explore the
mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on
Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene
of the Wnt signaling pathway, which has been identified as a marker of intestinal
stem cells and shown to be overexpressed in several human malignancies. Lgr5
expression was significantly correlated with lymph node metastasis, increased
depth of invasion, increased tumor size, advanced differentiation, higher AJCC
stage and poorer survival. Silencing of Lgr5 expression in the ESCC cell line
KYSE450 by small interfering RNA (siRNA) strongly inhibited cell proliferation,
migration and invasion ability, the expression of CSCs-related genes and Wnt/beta
catenin signaling. In addition, Lgr5 was highly expressed in ESCC spheroid body
cells, which were identified by high expression of CSCs-related genes, and high
tumorigenicity in vivo. Taken together, these results demonstrate that Lgr5
activation of Wnt/beta-catenin signaling is a potential mechanism to promote the
progression of ESCC and ESCC stem cell renewal, and Lgr5 may be used as a
molecular target for the development of treatments for ESCC.
PMID- 28404918
TI - Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.
AB - Glycans containing alpha-L-fucose participate in diverse interactions between
cells and extracellular matrix. High glycan expression on cell surface is often
associated with neoplastic progression. The lysosomal exoenzyme, alpha-L
fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is
down-regulated in highly aggressive and metastatic human tumors. However, the
role of FUCA-1 in tumor progression remains unclear. It is speculated that its
inactivation perturbs glycosylation of proteins involved in cell adhesion and
promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues
assayed by immunohistochemical (IHC) staining was high in normal thyroids and
papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly
differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA
expression from tissue samples and cell lines and protein expression levels and
enzyme activity in thyroid cancer cell lines paralleled those of IHC staining.
Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells
was inhibited by bovine alpha-L-fucosidase or Lewis antigens, thus pointing to an
essential role of fucose residues in the adhesive phenotype of this cancer cell
line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed
a less invasive phenotype versus the parental 8505C. These results demonstrate
that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues
and cell lines. As shown for other human cancers, the down-regulation of FUCA-1
correlates with increased aggressiveness of the cancer type. This is the first
report indicating that the down-regulation of FUCA-1 is related to the increased
aggressiveness of thyroid cancer.
PMID- 28404919
TI - Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK
cell-originated protein kinase.
AB - Excessive exposure to solar UV (SUV) is related with numerous human skin
disorders, such as skin inflammation, photoaging and carcinogenesis. T-LAK cell-
originated protein kinase (TOPK), an upstream of p38 mitogen-activated protein
kinase (p38) and c-Jun N-terminal kinases (JNKs), plays an important role in SUV
induced skin inflammation, and targeting TOPK has already been a strategy to
prevent skin inflammation. In this study, we found that the expression of TOPK,
phosphorylation of p38 or JNKs was increased in human solar dermatitis tissues.
The level of phosphorylation of p38 or JNKs increased in a dose and time
dependent manner in HaCat cells or JB6 Cl41 cells after SUV treatment. Paeonol is
an active component isolated from traditional Chinese herbal medicines, and MTS
(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium) assay
showed that it has no toxicity to cells. Microscale thermophoresis (MST) assay
showed that paeonol can bind TOPK ex vivo. In vitro kinase assay showed paeonol
can inhibit TOPK activity. Ex vivo studies further showed paeonol suppressed SUV
induced phosphorylation level of p38, JNKs, MSK1 and histone H2AX by inhibiting
TOPK activity in a time and dose dependent manner. Paeonol inhibited the
secretion of IL-6 and TNF-alpha in HaCat and JB6 cells ex vivo. In vivo studies
demonstrated that paeonol inhibited SUV-induced increase of TOPK, the
phosphorylation of p38, JNKs and H2AX, and the secretion of IL-6 and TNF-alpha in
Babl/c mouse. In summary, our data indicated a protective role of paeonol against
SUV-induced inflammation by targeting TOPK, and paeonol could be a promising
agent for the treatment of SUV-induced skin inflammation.
PMID- 28404920
TI - Noncanonical Wnt signaling plays an important role in modulating canonical Wnt
regulated stemness, proliferation and terminal differentiation of hepatic
progenitors.
AB - The liver provides vital metabolic, exocrine and endocrine functions in the body
as such pathological conditions of the liver lead to high morbidity and
mortality. The liver is highly regenerative and contains facultative stem cells
that become activated during injury to replicate to fully recover mass and
function. Canonical Wnt/beta-catenin signaling plays an important role in
regulating the proliferation and differentiation of liver progenitor cells during
liver regeneration. However, possible roles of noncanonical Wnts in liver
development and regeneration remain undefined. We previously established a
reversibly-immortalized hepatic progenitor cell line (iHPx), which retains
hepatic differentiation potential. Here, we analyze the expression pattern of the
essential components of both canonical and noncanonical Wnt signaling pathways at
different postnatal stages of mouse liver tissues and iHPx cells. We find that
noncanonical Wnt4, Wnt5a, Wnt9b, Wnt10a and Wnt10b, are highly expressed
concordantly with the high levels of canonical Wnts in late stages of liver
tissues. Wnt5a, Wnt9b, Wnt10a and Wnt10b are able to antagonize Wnt3a-induced
beta-catenin/TCF activity, reduce the stemness of iHPx cells, and promote hepatic
differentiation of liver progenitors. Stem cell implantation assay demonstrates
that Wnt5a, Wnt9b, Wnt10a and Wnt10b can inhibit cell proliferation and promote
hepatic differentiation of the iHPx progenitor cells. Our results strongly
suggest that noncanonical Wnts may play an important role in fine-tuning Wnt/beta
catenin functions during liver development and liver regeneration. Thus,
understanding regulatory mechanisms governing proliferation and differentiation
of liver progenitor cells may hold great promise to facilitate liver regeneration
and/or progenitor cell-based therapies for liver diseases.
PMID- 28404921
TI - Circulating miR-31 as an effective biomarker for detection and prognosis of human
cancer: a meta-analysis.
AB - PURPOSE: Circulating miR-31 was found to be associated with cancers detection and
prognosis. The present meta-analysis aimed to explore the effect of circulating
miR-31 on cancer detection and prognosis. METHOD: The studies were accessed using
multiple databases. RevMan5.3, Meta-DiSc 1.4, and STATA14.0 were used to estimate
the pooled effects, heterogeneity among studies, and publication bias. RESULTS: A
total of 14 studies with 1397 cancer patients and 1039 controls were included.
For the 12 prognostic tests, the adjusted pooled-AUC was 0.79 (95% CI: 0.73-0.86)
as the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative
likelihood ratio (NLR), diagnostic odd ratio (DOR) from 10 tests was 0.79 (95%
CI: 0.76-0.82), 0.79 (95% CI: 0.76-0.82), 3.81 (95% CI: 2.90-5.01), 0.26 (95% CI:
0.20-0.35), and 16.81 (95% CI: 9.67-29.25), respectively. For the 5 prognosis
analyses, the pooled HR (hazard ratio) of overall survival (OS) was 1.55 (95% CI
1.30-1.86) for high versus low circulating miR-31 expression. However, high
expression of circulating miR-31 did not significantly increase the risk of poor
differentiation (pooled OR=1.39, 95% CI: 0.56-3.47) and LNM (pooled OR=3.46, 95%
CI: 0.96-12.42) in lung cancer. CONCLUSION: Circulating miR-31 is an effective
biomarker and could be used as a component of miRs signature for cancer detection
and prognosis surveillance.
PMID- 28404922
TI - Adipophilin as prognostic biomarker in clear cell renal cell carcinoma.
AB - OBJECTIVE: To study the expression of adipophilin (PLIN2), a lipid storage
associated cell protein, in different subtypes of renal cell cancer and to
elucidate its prognostic value. MATERIALS AND METHODS: Two-hundred-seventy-five
patients with renal cell carcinoma (RCC) were included in this study.
Immunohistochemistry with a polyclonal antibody to adipophilin was used on the
tissue microarray (formalin-fixed, paraffin-embedded tissue) for detection of
adipophilin. Median follow-up time was 91 (range 1-159) months in the whole
cohort and 100 (1-159) months for patients with clear-cell RCC. Additional
validation for adipophilin was performed using publicly available gene expression
data for clear cell RCC from The Cancer Genome Atlas (TCGA). RESULTS: Adipophilin
expression was detected in 14.3% of papillary RCC, in 0% of chromophobe RCC and
in 58.7% of clear-cell RCC in the cytoplasm or at the membrane. Only membrane
expression was correlated with other clinical parameters (pT-stage, pN-stage, R
status, sex) and showed a prognostic significance in univariate analysis with
regard to overall survival of patients with clear cell subtype (HR 2.90, 95% CI
1.55-5.42, p=0.001), which failed significance on multivariate analysis. mRNA
expression of PLIN2 on TCGA data using best selected cut-off was prognostically
significant in both univariate (HR 1.76, 95% CI 1.28-2.42, p = 0.0005) and
multivariate analyses (HR 1.46, 95% CI 1.05-2.04, p = 0.0257). CONCLUSIONS:
Adipophilin is a novel and still understudied prognostic biomarker in clear cell
renal cell carcinoma which deserves further study.
PMID- 28404923
TI - Down-regulation of miR-146b-5p by long noncoding RNA MALAT1 in hepatocellular
carcinoma promotes cancer growth and metastasis.
AB - MicroRNAs play an important role in liver cancer genesis and progression. In this
study, we identified down-regulation of miR-146b-5p associated with tumor growth,
metastasis and poor survival in hepatocellular carcinoma (HCC) patients. miR-146b
5p could suppress proliferation, migration, and invasion and induced apoptosis in
vitro and in vivo. Remarkably, TNF receptor associated factor 6 (TRAF6) was
confirmed as a direct target of miR-146b-5p in HCC and miR-146b-5p exerted the
tumor suppression roles through inhibiting the phosphorylation of Akt mediated by
TRAF6. Furthermore, we identified long non-coding RNA MALAT1 as a molecular
sponge of miR-146b-5p to down-regulate its expression in HCC. In general, our
results indicate that miR-146b-5p inhibits tumor growth and metastasis of HCC by
targeting TRAF6 mediated Akt phosphorylation.
PMID- 28404924
TI - Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal
adenocarcinoma.
AB - Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal
adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC
and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro
and in murine xenografts. The CDK9 expression was significantly higher in EAC as
compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4
reduced proliferation by 37% at day 4, increased apoptosis at 48 hours and
induced G1 cell cycle arrest at 48 hours (58.4% vs. 45.8%) compared to controls
SKGT4 cells. SKGT4-shCDK9 cell-derived tumors were significantly smaller than
control SKGT4-derived tumors in xenografts (72.89mm3 vs. 270mm3). Pharmaceutical
inhibition of CDK9 by Flavopiridol (0.1um for 48 hours) and CAN508 (20 and 40um
for 72 hours) induced significant reduction in proliferation and 2-fold increase
in apoptosis in SKGT4, FLO1 and OE33 cells. In xenograft models, CAN508 (60
mg/kg/dayx10 days) and Flavopiridol (4mg/kg/dayx10 days) caused 50.8% and 63.1%
reduction in xenograft tumors as compared to control on post-treatment day 21.
Reduction of MCL-1 and phosphorylated RNA polymerase II was observed with
transient shCDK9 in SKGT4 cells but not with stable shCDK9. CAN508 (20 and 40 um)
and Flavopiridol (0.1, 0.2 and 0.3 um) for 4 hours showed reduction in MCL-1 mRNA
(84% and 96%) and protein. Mcl-1 overexpression conferred resistance to
Flavopiridol (0.2 um or 0.4 um for 48 hours) and CAN 508 (20 or 40um for 72
hours). Chromatin immunoprecipitation demonstrated significant reduction of
binding of transcriptional factor HIF-1alpha to MCL-1 promoter in FLO-1 cells by
CDK9 inhibitors.
PMID- 28404925
TI - MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses
tumor growth, migration and invasion by directly targeting AKT2.
AB - Our previous studies have suggested a protective role for H. pylori infection in
the prognosis of gastric cancer. Based on those findings, we hypothesized that H.
pylori-positive and -negative gastric cancers may exhibit different growth
patterns and pathobiological behaviors, indicating different mechanisms of cancer
progression. By microarray analysis, we studied miRNAs expression profiles in 42
gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori
negative groups. Luciferase reporter assay and western blot were used to examine
the potential target genes of the interested miRNA. In the present study, 53
miRNAs were significantly differentially expressed in H. pylori-positive and
negative gastric cancer tissues. We investigated the expression and function of
one candidate, miR-143-3p, which was the most significantly increased miRNA in H.
pylori-positive gastric cancer tissues. We observed that miR-143-3p expression
was significantly decreased in gastric cancer tissues and cells, which correlated
with late stage and lymph node metastasis. Using gain- and loss-of-function
experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell
growth, apoptosis, migration and invasion. We further characterized AKT2 as a
novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the
effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143
3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration
and invasion through directly targeting AKT2 gene. Further investigation is
warranted to characterize the mechanisms underlying gastric cancer progression
and may eventually contribute to its therapy.
PMID- 28404926
TI - Association of tumor TROP2 expression with prognosis varies among lung cancer
subtypes.
AB - TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers.
Emerging evidence suggests that TROP2-targeting therapies are efficacious and
safe in patients with multiple prior treatments. TROP2 is a promising target for
lung cancer treatment; however, little is known regarding the association of
TROP2 expression with clinicopathological/molecular features, including
prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma,
squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for
the membranous expression of TROP2 using immunohistochemistry. High TROP2
expression was observed in 64% (172/270) of adenocarcinomas, 75% (150/201) of
SqCCs, and 18% (21/115) of HGNETs. Intriguingly, the association of TROP2
expression with mortality was dependent on the lung cancer subtype. High TROP2
expression was associated with higher lung cancer-specific mortality in
adenocarcinomas [univariable hazard ratio (HR) = 1.60, 95% confidence interval
(CI) = 1.07-2.44, P = 0.022)], but not in SqCCs (univariable HR = 0.79, 95% CI =
0.35-1.94, P = 0.79). In HGNETs, high TROP2 expression was associated with lower
lung cancer-specific mortality in both univariable and multivariable analyses
(multivariable HR = 0.13, 95% CI = 0.020-0.44, P = 0.0003). Our results suggest a
differential role for TROP2 in different lung cancer subtypes.
PMID- 28404927
TI - Prognostic role of B7-H4 in patients with non-small cell lung cancer: A meta
analysis.
AB - B7 homolog 4 (B7-H4) has been recently reported to be a prognostic marker in non
small cell lung cancer (NSCLC) in some studies. However, the results remained
conflicting. Thus, we aimed to comprehensively assess the association between B7
H4 expression and prognosis of NSCLC patients by performing a meta-analysis.
Relevant publications were thoroughly searched of PubMed, Embase, Web of Science
and China National Knowledge Infrastructure (CNKI). The pooled odds ratios (ORs)
and hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to
evaluate the effects. A total of 9 studies comprising 1444 patients were included
in this meta-analysis. B7-H4 overexpression was associated with presence of lymph
node metastasis (OR=3.59, 95%CI=2.39-5.38, p<0.001; fixed effect), advanced TNM
stage (OR=2.36, 95%CI=1.2-4.67, p=0.013; random effect), and poor differentiation
(OR=2.11, 95%CI=1.12-3.99, p=0.021; fixed effect). However, B7-H4 had no
significant correlation with gender, age or histology in NSCLC. Furthermore, in a
fixed effects model, the results indicated that B7-H4 overexpression was
significantly associated with poor OS (HR=2.03, 95%CI=1.41-2.92, p<0.001). This
meta-analysis demonstrated that high B7-H4 expression is an unfavorable
prognostic factor in NSCLC. Because few studies were included for meta-analysis
and almost all included studies were performed on Chinese patients, therefore;
large scale prospective studies are needed to verify our results.
PMID- 28404928
TI - Preoperative serum lipids as prognostic predictors in esophageal squamous cell
carcinoma patients with esophagectomy.
AB - This study was to evaluate the prognostic significance of serum lipids in
esophageal squamous cell carcinoma patients who underwent esophagectomy.
Preoperative serum lipids were collected from 214 patients who were diagnosed
with esophageal squamous cell carcinoma. All of the patients received
esophagectomy in Qilu Hospital of Shandong University from January 2007 to
December 2008. The records and data were analyzed retrospectively. We found that
low total cholesterol (for T stage, p = 0.006; for TNM stage, p = 0.039) and low
density lipoprotein cholesterol (for T stage, p = 0.031; for TNM stage, p =
0.035) were associated with advanced T stage and TNM stage. Kaplan-Meier survival
analysis indicated that low total cholesterol and low-density lipoprotein
cholesterol were associated with shorter disease-free survival(for total
cholesterol, p = 0.045; for low-density lipoprotein cholesterol, p < 0.001) and
overall survival (for total cholesterol, p = 0.043; for low-density lipoprotein
cholesterol, p < 0.001). Lower low-density lipoprotein cholesterol/high-density
lipoprotein cholesterol ratio (LHR) indicated poorer disease-free survival and
overall survival (both p < 0.001). In the multivariate analysis, low-density
lipoprotein cholesterol and LHR were independent prognostic factors for disease
free survival and overall survival. In conclusion, our study indicated that
preoperative serum total cholesterol and low-density lipoprotein cholesterol are
prognostic factors for esophageal squamous cell carcinoma patients who underwent
esophagectomy. LHR can serve as a promising serum lipids-based prognostic
indicator.
PMID- 28404929
TI - Hematology oncology practice in the Asia-Pacific APHCON survey results from the
6th international hematologic malignancies conference: bridging the gap 2015,
Beijing, China.
AB - This report serves as a snapshot of the state-of-knowledge in the Asia Pacific
(APAC) Hematology Oncology community, and establishes a baseline for longitudinal
investigations to follow changes in best practices over time. The objective of
this study was to understand the approach to hematologic diseases, common
standards of care and best practices, issues that remain controversial or
debated, and educational or resource gaps that warrant attention. We used mobile
application to disseminate and distribute questionnaires to delegates during the
6th international hematologic malignancies conference hosted by the APAC
Hematology Consortium at Beijing, China. User responses were collected in an
anonymous fashion. We report survey results in two ways: the overall responses,
and responses as stratified between Chinese physicians and "Other" represented
nationalities. Overall geographical concordance in survey responses was positive
and strong. Perhaps more interesting than instances of absolute agreement, these
data provide a unique opportunity to identify topics in which physician knowledge
or opinions diverge. We assigned questions from all modules to broad categories
of: patient information; diagnosis; treatment preference; transplantation; and
general knowledge/opinion. On average, we observed a geographic difference of 15%
for any particular answer choice, and this was fairly constant across survey
modules. These results reveal utility and need for widespread and ongoing
initiatives to assess knowledge and provide evidence-based education in real
time. The data will be made more valuable by longitudinal participation, such
that we can monitor changes in the state of the art over time.
PMID- 28404930
TI - MicroRNA regulation of progesterone receptor in breast cancer.
AB - Hormone receptor status is of significant value when deciding on anti-estrogenic
adjuvant therapy for breast cancer tumors. However, while estrogen receptor (ER)
regulation was intensively studied, the regulation of progesterone receptor (PR)
levels has not been extensively investigated. MicroRNAs (miRNAs, miRs) are post
transcriptional negative regulators of gene expression involved in diverse
cellular processes. The aim of this study was to identify miRNAs that regulate PR
in breast cancer.We mapped potential miRNA binding sites for miR-181a, miR-23a
and miR-26b on PR mRNA and demonstrated a direct regulation of PR by these three
miRNAs by in-vitro Luciferase binding assays. Over-expression of each miRNA in
MCF-7 cells resulted in a reduction in the expression levels of PR mRNA. Then,
expression levels of these miRNAs were measured in Formalin-Fixed, Paraffin
Embedded (FFPE) samples of 29 ER-positive breast cancer tumors and adjacent
normal breast tissues. A significant reciprocal correlation between PR mRNA and
the miRNA levels were identified suggesting a role for miR-181a, miR-23a and miR
26b in PR regulation in breast cancer. Moreover, the average expression fold
changes of the three miRNAs between cancerous and normal tissues displayed an
opposite trend when analyzing according to Immuno-histochemistry(IHC) status.
Furthermore, miR-181a and miR-26b were found to be over-expressed in most tumor
tissues supporting their role in ER-positive breast cancer development. We
conclude that miR-181a, miR-23a and miR-26b act as negative regulators of PR
expression in ER-positive breast cancer. The diagnostic and prognostic potential
of these miRNAs in breast cancer should be further evaluated.
PMID- 28404931
TI - A retrospective analysis of the utility of endocervical curettage in screening
population.
AB - The performance of endocervical curettage (ECC) is a dispute in population
screening programs. Data of 3,460 women referred to colposcopy examination and
had completed pathological results in the Shanxi Province Cervical Cancer
Screening Study I and II were reviewed. Among them, 0.6% and 2.7% women were
identified as the histopathological confirmed high-grade squamous intraepithelial
lesion or worse (HSIL+) by ECC alone or both ECC and quadrants biopsy
respectively. Age, cytology, and colposcopy impression are the impact factors for
the HSIL+ yield of ECC (P<0.05). The age-adjusted odds ratio for cytology and
colposcopic impression were 5.283 (95%CI: 3.989-6.997) and 3.609 (95%CI: 2.910
4.476) respectively. In low-grade squamous intraepithelial lesion cytology and
abnormal colposcopy, no additional HSIL+ was found by ECC. In low-grade squamous
intraepithelial lesion cytology but normal colposcopy, the additional yield was
0.6%, 0.8% and 1.1% for the three age groups respectively. In high-grade squamous
intraepithelial lesion or worse cytology, the additional HSIL+ yield by ECC
ranged between 1.4% and 6.6%. We conclude that the performance of ECC increases
with age, the severity of cytology, and colposcopic impression. For women 35
years and older, ECC should be performed if the cytological finding is high-grade
or worse in cervical cancer screening program.
PMID- 28404932
TI - CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric
cancer and is associated with poor prognosis.
AB - C-terminal binding protein-2 (CtBP2), a transcriptional corepressor, has been
reported to correlate with tumorigenesis and progression and predict a poor
prognosis in several human cancers. However, few studies on CtBP2 in gastric
cancer (GC) have been performed. In this research, we evaluated the correlations
between CtBP2 expression and the clinicopathological characteristics, as well as
prognosis of GC patients. The effects of silencing CtBP2 expression on GC cells
biology activity were also assessed. The results showed that CtBP2 was
overexpressed in GC tissues and closely correlated with poor differentiation,
advanced tumor stage and poor prognosis in GC patients. CtBP2 induced epithelial
to-mesenchymal transition (EMT) and repressed PTEN to increase proliferation
rate, migration, and invasion in GC cells. Silencing CtBP2 inhibited GC growth in
nude mice model. In conclusion, CtBP2 is overexpressed in GC and may accelerate
GC tumorigenesis and metastasis, which could represent an independent prognostic
marker and promising therapeutic target for GC.
PMID- 28404933
TI - Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts
poor prognosis.
AB - BACKGROUND: Definitive radiation therapy (RT) (with or without cisplatin-based
chemotherapy) is one of the most effective treatments for cervical squamous cell
carcinoma (CSCC), but efficacy is limited due to resistance. In the present
study, we investigated the relationship between the expression of Aurora kinase A
(Aurora-A, AURKA)and response to RT in patients with CSCC. METHODS: The
expression of Aurora-A in biopsy specimens of untreated primary tumors in 129
Uyghur patients with CSCC was investigated immunohistochemically. Primary
treatment in these patients was definitive radical RT, which consisted of pelvic
RT plus brachytherapy (total point A dose:70-85 Gy) (with or without cisplatin
based chemotherapy). The prognostic value of tumoral Aurora-A expression and
patients' clinical outcomes were evaluated. RESULTS: Aurora-A expression was
significantly associated with lymph node metastasis (P<0.001), large tumor size
(P<0.001), low hemoglobin (Hb) level (P=0.011) and recurrence (P<0.001), but not
other clinicopathological factors. Definitive RT was unfavorable in patients with
high Aurora-A expression (P < 0.001). In 129 enrolled patients, lymph node
metastasis, large tumor size, low Hb level, and AURKA overexpression were
prognostic factors for both recurrent free survival (RFS) and overall survival
(OS) in univariate analysis. However, only high AURKA expression was an adverse
independent risk factor for both RFS (hazard ratio, 3.953; 95% CI, 1.473-10.638;
P = 0.006) and OS (hazard ratio 9.091; 95%CI 2.597-32.258; P<0.001) in
multivariate analyses. CONCLUSIONS: Aurora-A may serve as a predictive biomarker
of radiation response and a therapeutic target to reverse radiation therapy
resistance.
PMID- 28404934
TI - Increased serum resistin level is associated with coronary heart disease.
AB - To explore the relationship between the serum resistin level and different types
of coronary heart diseases (CHD). Literature was retrieved by formal searching of
PubMed, Web of Science, Google Scholar, the Cochrane Library, Wanfang Data, China
Biological Medicine Database (SinoMed) and China National Knowledge
Infrastructure (CNKI) and by hand searching of reference lists of related
articles. RevMan5.3 statistical software was utilized for processing and
analysis. A total of 22 literatures involving 2070 subjects were included. Meta
analysis showed that the level of serum resistin in the patients with stable
angina (SA), unstable angina(UA) or acute myocardial infarction (AMI) were
significantly higher than those of normal controls, respectively [SMD(95% CI)were
1.97(1.15, 2.79), 2.54(1.76, 3.31), and 3.62(2.62, 4.62), all P<0.00001]. Serum
resistin level in patients with UA or AMI was higher than those in patients with
SA, respectively [SMD=0.90, 95CI(0.28,1.52), P=0.005], [SMD=2.28, 95%CI(0.74,
3.82), P=0.004].The level of serum resistin in patients with AMI was also higher
than those in patients with UA [SMD=1.22, 95%CI(0.58, 1.85), P=0.0002]. The study
demonstrated that increased serum resistin level is significantly associated with
the severity of CHD.
PMID- 28404935
TI - Outcomes of metastatic spinal cord compression secondary to primary
hepatocellular carcinoma with multidisciplinary treatments.
AB - Few studies have reported progression-free survival (PFS) and overall survival
(OS) of Metastatic spinal cord compression (MSCC) patients with primary
hepatocellular carcinoma (HCC) following surgery and adjuvant therapies. Enrolled
in this study were 155 MSCC patients with primary HCC who received surgery and
adjuvant therapies between 2000 and 2015. Kaplan-Meier methods and Cox's
proportional hazards regression mode were performed to investigate the clinical
features and prognostic factors affecting PFS and OS. The median PFS and OS was
7.0 months and 9.7 months, respectively. 92.9% patients responded well to surgery
according to the Visual Analogue Scale, Frankel Score and postoperative
complication occurrences. 68 (43.9%) patients who received circumferential
decompression achieved better PFS than the remaining 87 (56.1%) patients who
received laminectomy. Favorable outcomes were achieved after surgery during the
perioperative period. Circumferential decompression was associated with better
PFS than laminectomy. The postoperative Frankel Score E, Eastern Cooperative
Oncology Group performance score of 1 or 2, no visceral metastasis,
administration of postoperative radiation and the use of Sorafenib were found to
be significant predictors of better PFS and OS. Patients who previously underwent
resection of primary HCC with/without liver transplantation tended to have a
better OS.
PMID- 28404936
TI - Systematic identification and comparison of expressed profiles of lncRNAs and
circRNAs with associated co-expression and ceRNA networks in mouse germline stem
cells.
AB - Accumulating evidence indicates that long noncoding RNAs (lncRNAs) and circular
RNAs (circRNAs) involve in germ cell development. However, little is known about
the functions and mechanisms of lncRNAs and circRNAs in self-renewal and
differentiation of germline stem cells. Therefore, we explored the expression
profiles of mRNAs, lncRNAs, and circRNAs in male and female mouse germline stem
cells by high-throughput sequencing. We identified 18573 novel lncRNAs and 18822
circRNAs in the germline stem cells and further confirmed the existence of these
lncRNAs and circRNAs by RT-PCR. The results showed that male and female germline
stem cells had similar GDNF signaling mechanism. Subsequently, 8115 mRNAs, 3996
lncRNAs, and 921 circRNAs exhibited sex-biased expression that may be associated
with germline stem cell acquisition of the sex-specific properties required for
differentiation into gametes. Gene Ontology (GO) and KEGG pathway enrichment
analyses revealed different functions for these sex-biased lncRNAs and circRNAs.
We further constructed correlated expression networks including coding-noncoding
co-expression and competing endogenous RNAs with bioinformatics. Co-expression
analysis showed hundreds of lncRNAs were correlated with sex differences in mouse
germline stem cells, including lncRNA Gm11851, lncRNA Gm12840, lncRNA
4930405O22Rik, and lncRNA Atp10d. CeRNA network inferred that lncRNA Meg3 and
cirRNA Igf1r could bind competitively with miRNA-15a-5p increasing target gene
Inha, Acsl3, Kif21b, and Igfbp2 expressions. These findings provide novel
perspectives on lncRNAs and circRNAs and lay a foundation for future research
into the regulating mechanisms of lncRNAs and circRNAs in germline stem cells.
PMID- 28404937
TI - Genetic polymorphisms are associated with the risk of gastric and colorectal
cancers in a Han Chinese population.
AB - Here, we genotyped eleven single-nucleotide polymorphisms (SNPs) and evaluated
their association with the risk of developing gastric cancer (GC) or colorectal
cancer (CRC) in 1,790 Han Chinese participants (588 GC patients, 499 CRC
patients, and 703 healthy controls). Statistically analysis showed that the "C"
allele of rs2689154 in MIPEPP2 was associated with a decreased risk of GC (odds
ratio [OR] = 0.81, 95 % confidence interval [CI]: 0.66-0.99, P = 0.041), whereas
the "T" allele of rs12615966 in LOC284998 was associated with a 1.29-fold
increase in the risk of GC (OR = 1.29, 95% CI: 1.03-1.63, P = 0.029).
Additionally, genetic model analyses showed that rs2689154 was associated with a
reduced risk of GC under the recessive model (adjusted OR = 0.46, 95% CI: 0.22
0.98, P = 0.037), and rs12615966 in FOXF1 was associated with an increased risk
of GC in both the dominant and log-additive models after adjusted for age and
gender (adjusted OR = 1.36, 95% CI: 1.02-1.81, P = 0.033; adjusted OR = 1.36, 95%
CI: 1.05-1.75, P = 0.018, respectively). We also observed that rs2178146 in FOXF1
was associated with an increased risk of CRC in the recessive model (adjusted OR
= 1.90, 95% CI: 1.05-3.45, P = 0.034). Our results confirmed that rs2689154 in
MIPEPP2 was significantly decreased GC risk, but rs12615966 in LOC284998 was
significantly increased GC risk, and rs2178146 in FOXF1 was associated with
increased CRC risk in the Han Chinese population.
PMID- 28404938
TI - A meta-analytic review of the relationship of cancer coping self-efficacy with
distress and quality of life.
AB - Self-efficacy for coping with cancer is a specific construct that refers to
behaviors that occur in the course of dealing with a cancer diagnosis, cancer
treatments, and transitioning to survivorship. One of the more widely used
measures of self-efficacy for coping strategies with cancer is the Cancer
Behavior Inventory. The following general questions provide a framework for this
research: 1. Is self-efficacy for coping with cancer related to distress and
quality of life of a cancer patient?. 2. Do self-efficacy for coping with cancer
and the target psychological outcomes (i.e., distress and quality of life) change
in longitudinal studies, with or without intervention? One-hundred eighty studies
cited the different versions of the Cancer Behavior Inventory and 47 used the
scale. Result showed an inverse relationship between self-efficacy for coping
with cancer and distress, and a positive relationship between self-efficacy for
coping with cancer and Quality of Life, both with a large effect size. The strong
relationship of self-efficacy and outcomes, resulted of the specificity of the
instrument, which targets specific coping strategies that are closely aligned
with positive outcomes in adjusting to cancer. However, the results are
consistent with the theory, which states that compared to those with low
efficacy, highly efficacious people demonstrate less anxiety and better
adjustment in stressful situations and consistent with prior results in which
self-efficacy is positively related to quality of life.
PMID- 28404939
TI - delta-Tocotrienol, a natural form of vitamin E, inhibits pancreatic cancer stem
like cells and prevents pancreatic cancer metastasis.
AB - The growth, metastasis, and chemotherapy resistance of pancreatic ductal
adenocarcinoma (PDAC) is characterized by the activation and growth of tumor
initiating cells in distant organs that have stem-like properties. Thus,
inhibiting growth of these cells may prevent PDAC growth and metastases. We have
demonstrated that delta-tocotrienol, a natural form of vitamin E (VEDT), is
bioactive against cancer, delays progression, and prevents metastases in
transgenic mouse models of PDAC. In this report, we provide the first evidence
that VEDT selectively inhibits PDAC stem-like cells. VEDT inhibited the
viability, survival, self-renewal, and expression of Oct4 and Sox2 transcription
factors in 3 models of PDAC stem-like cells. In addition, VEDT inhibited the
migration, invasion, and several biomarkers of epithelial-to-mesenchymal
transition and angiogenesis in PDAC cells and tumors. These processes are
critical for tumor metastases. Furthermore, in the L3.6pl orthotopic model of
PDAC metastases, VEDT significantly inhibited growth and metastases of these
cells. Finally, in an orthotopic xenograft model of human PDAC stem-like cells,
we showed that VEDT significantly retarded the growth and metastases of
gemcitabine-resistant PDAC human stem-like cells. Because VEDT has been shown to
be safe and to reach bioactive levels in humans, this work supports investigating
VEDT for chemoprevention of PDAC metastases.
PMID- 28404940
TI - RNAi-mediated inhibition of Lgr5 leads to decreased angiogenesis in gastric
cancer.
AB - Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel
gastric cancer marker. However, it is unclear whether it can play roles in tumor
angiogenesis. In this study, we aim to investigate the role of Lgr5 on gastric
cancer angiogenesis. Lgr5, VEGF expression levels and microvessel density (MVD)
were detected in tumor tissue. Then, Lgr5 mRNA was downregulated by small
interference RNA technique. Western blotting and real-time quantitative PCR (qRT
PCR) were performed to detect the expression of Lgr5 and VEGF protein and mRNA in
Lgr5 siRNA-transfected gastric cancer cells. The effect of silencing Lgr5 on
angiogenesis was examined by assessing human umbilical vein endothelia cell
(HUVEC) capillary tube formation. The results indicated that Lgr5 expression was
upregulated in gastric cancer and positively correlated with VEGF (r=0.305,
P=0.001) and MVD (r=0.312, P=0.001). Silencing of Lgr5 expression resulted in
suppression of VEGF mRNA and protein (all P=0.001). Moreover, when HUVECs were
stimulated with conditioned medium from Lgr5 siRNA-transfected gastric cancer
cells, tube formation was significantly decreased (2.51 +/- 0.19 mm/mm2) compared
with the treatment with regular cell culture medium (DMEM) (7.34 +/- 0.30 mm/mm2)
or medium from control siRNA-transfected cells (7.18 +/- 0.33 mm/mm2) (all
P=0.001). In conclusion, Lgr5 plays important roles in angiogenesis. Lgr5
specific siRNA could be designed into an effective therapeutic agent to inhibit
gastric cancer angiogenesis.
PMID- 28404941
TI - Citrinin exposure affects oocyte maturation and embryo development by inducing
oxidative stress-mediated apoptosis.
AB - Citrinin is one of the mycotoxins and has been shown to have various toxic
effects in animals and humans. Although previous study showed the toxic effects
of citrinin on the female reproductive system, especially on oocyte maturation,
however, the causes or mechanism of citrinin on oocyte quality is unclear. In
present study we deeply investigated this topic. We found thatcitrinin toxin
exposure inhibited mouse oocyte maturation and early embryo development. Further
investigation showed that the actin distribution in oocytes and embryos was
disrupted, and the reduced expression of actin nucleator ARP2 expression in the
oocyte cortex further confirmed this. We also found that meiotic spindle
morphology was abnormal after citrinin treatment. These results indicated that
citrinin toxin exposure could disrupt cytoskeleton dynamics to affect oocyte
maturation and early embryo development. We also examined the ROS level and early
apoptosis marker Annexin signals, and the results showed that both levels
increased, indicating that citrinin induced oxidative stress and further resulted
in oocyte early apoptosis. Taken together, our results indicated that citrinin
toxin exposure could reduce mouse oocyte maturation and early embryo development
capability by affecting cytoskeletal dynamics, which may be due to the oxidative
stress induced early apoptosis.
PMID- 28404942
TI - A novel bioactive osteogenesis scaffold delivers ascorbic acid, beta
glycerophosphate, and dexamethasone in vivo to promote bone regeneration.
AB - Ascorbic acid, beta-glycerophosphate, and dexamethasone have been used in
osteogenesis differentiation medium for in vitro cell culture, nothing is known
for delivering these three bioactive compounds in vivo. In this study, we
synthesized a novel bioactive scaffold by combining these three compounds with a
lysine diisocyanate-based polyurethane. These bioactive compounds were released
from the scaffold during the degradation process. The cell culture showed that
the sponge-like structure in the scaffold was critical in providing a large
surface area to support cell growth and all degradation products of the polymer
were non-toxic. This bioactive scaffold enhanced the bone regeneration as
evidenced by increasing the expression of three bone-related genes including
collagen type I, Runx-2 and osteocalcin in rabbit bone marrow stem cells (BMSCs)
in vitro and in vivo. The osteogenesis differentiation of BMSCs cultured in this
bioactive scaffold was similar to that in osteogenesis differentiation medium and
more extensive in this bioactive scaffold compared to the scaffold without these
three bioactive compounds. These results indicated that the scaffold containing
three bioactive compounds was a good osteogenesis differentiation promoter to
enhance the osteogenesis differentiation and new bone formation in vivo.
PMID- 28404943
TI - Melatonin protects against blood-brain barrier damage by inhibiting the TLR4/ NF
kappaB signaling pathway after LPS treatment in neonatal rats.
AB - Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain
barrier (BBB) which leads to inflammatory responses and neuronal cell death,
resulting in brain secondary damage. Previous studies showed that melatonin
produced potent neuroprotective effects in neonatal hypoxic-ischaemic models.
However, the relationship between BBB disruption and melatonin in HII was still
unclear. The present study therefore investigated the beneficial effects of
melatonin on BBB after HII and the underlying mechanisms. HII animal model was
conducted by receiving lipopolysaccharide followed by 90 min hypoxia-ischaemia in
postnatal day 2 Sprague-Dawley rat pups. Melatonin was injected intraperitoneally
1 h before lipopolysaccharide injection and then once a day for 1 week to
evaluate the long-term effects. In this study, we demonstrated that melatonin
administration inhibited the disruption of BBB permeability and improved the
white matter recovery in HII model rats. Melatonin significantly attenuated the
degradation of junction proteins and the neuroprotective role was related to the
inhibition of microglial toll-like receptor 4/ nuclear factor-kappa B signaling
pathway both in vivo and in vitro. Taken together, our data demonstrated that
therapeutic strategies targeting inflammation might be suitable for the therapy
of preserving BBB integrity after HII.
PMID- 28404944
TI - Recombinant methioninase effectively targets a Ewing's sarcoma in a patient
derived orthotopic xenograft (PDOX) nude-mouse model.
AB - Methionine dependence is due to the overuse of methionine for aberrant
transmethylation reactions in cancer. Methionine dependence may be the only
general metabolic defect in cancer. In order to exploit methionine dependence for
therapy, our laboratory previously cloned L-methionine alpha-deamino-gamma
mercaptomethane lyase [EC 4.4.1.11]). The cloned methioninase, termed recombinant
methioninase, or rMETase, has been tested in mouse models of human cancer cell
lines. Ewing's sarcoma is recalcitrant disease even though development of
multimodal therapy has improved patients'outcome. Here we report efficacy of
rMETase against Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX)
model. The Ewing's sarcoma was implanted in the right chest wall of nude mice to
establish a PDOX model. Eight Ewing's sarcoma PDOX mice were randomized into
untreated control group (n = 4) and rMETase treatment group (n = 4). rMETase (100
units) was injected intraperitoneally (i.p.) every 24 hours for 14 consecutive
days. All mice were sacrificed on day-15, 24 hours after the last rMETase
administration. rMETase effectively reduced tumor growth compared to untreated
control. The methionine level both of plasma and supernatants derived from
sonicated tumors was lower in the rMETase group. Body weight did not
significantly differ at any time points between the 2 groups. The present study
is the first demonstrating rMETase efficacy in a PDOX model, suggesting potential
clinical development, especially in recalcitrant cancers such as Ewing's sarcoma.
PMID- 28404945
TI - Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces
tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell
carcinoma.
AB - Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and
clinical outcomes. We previously showed that conditioned medium (CM) from CAFs
induces proliferation and motility of esophageal squamous cell carcinoma (ESCC)
cells. Here, we investigated the molecular mechanisms by which the CAF-secreted
proteins induce ESCC development and progression. Using antibody arrays, we
identified urokinase plasminogen activator (uPA) as one of the main proteins
whose release was increased in CAFs compared to normal fibroblasts (NFs).
Immunohistochemical analysis of pathological sections showed that uPA-positive
cells were localized at the boundaries of tumor and stroma tissues, in stroma
between tumor nests, and within the tumors. Increased stromal uPA levels (132/146
cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC
patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell
proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways.
In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These
results suggest that uPA released from stroma, and especially from CAFs, might be
a predictive marker for ESCC diagnosis and prognosis, as well as an effective
therapeutic target.
PMID- 28404946
TI - CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic
microenvironment and treatment response.
AB - Osteosarcoma (OS) is the most common malignant bone tumor in children and
adolescents. The present study investigated the expression of Cytochrome P-450
(CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from
OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post
chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis
and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal
lung tissues were used as control. We also investigated in five OS cell lines the
modulation of CYPs expression by cisplatin, doxorubicin and methotrexate. As
result, the adjacent lung specimens presented CYP1A2 overexpression compared to
the normal lung (p=0.0256). Biopsy specimens presented lower CYP3A4 expression
than normal bone (p=0.0314). The overexpression of both CYP1A2 and CYP3A4 in post
chemotherapy specimens were correlated with better event free-survival (p=0.0244)
and good response (p=0.0484), respectively. Furthermore, in vitro assays revealed
that CYP1A2 was upregulated by doxorubicin (p=0.0034); CYP3A4 was upregulated by
cisplatin, doxorubicin and methotrexate (p=0.0004, p=0.0024, p<0.0001,
respectively); and CYP3A5 was downregulated by doxorubicin (p=0.0285) and
upregulated in time-dependent manner by methotrexate (p=0.0239). In conclusion,
our findings suggest that CYP genes play an important role in OS tumorigenesis,
at primary and metastatic sites, as well in treatment response.
PMID- 28404947
TI - Identification of urine biomarkers associated with lung adenocarcinoma.
AB - Lung adenocarcinoma (LAC) progression is accompanied by changes in protein levels
that may be reflected in body fluids, such as urine. Urine collected from LAC
patients (n=34) and healthy controls (n=36) was analyzed via matrix-assisted
laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)
combined with weak cationic exchange magnetic beads. The results revealed 76
urinary polypeptides significantly different between LAC patients and normal
controls (P<0.05). Twenty-two of these peptides were up-regulated and 54 were
down-regulated. Thirteen peptides had average peak intensities >600. Twelve of
these 13 peptides were successfully identified using nano-liquid chromatography
tandem MS. Receiver operating characteristic analyses identified seven peptides
with superior LAC diagnostic performances. Immunohistochemical staining in 20
paired LAC and adjacent normal tissues showed that IGKC, AAT, SH3BGRL3,
osteopontin and gelsolin levels were higher in LAC tissues than in adjacent
tissuesand were closely associated with LAC. Urinary peptides assessments may
thus provide a novel, noninvasive, repeatable method for detecting and monitoring
LAC. New, low-cost detection methods and bioinformatics tools are therefore
urgently needed for the analysis of low abundance proteins and peptides in body
fluids.
PMID- 28404949
TI - Metabolomics uncovers a link between inositol metabolism and osteosarcoma
metastasis.
AB - Cancer development and progression are characterized by complex molecular events.
The acquisition of these events is primarily believed to result from alterations
in gene and protein expression/function. Recent studies have also suggested the
role of metabolic alterations, or "metabolic reprogramming," that may similarly
contribute to these events. Indeed, our previous investigations in osteosarcoma
(OS) identified metabolic changes uniquely linked to metastasis. Based on those
findings, here we sought to build a more detailed understanding of the specific
alterations in metabolites or metabolic pathways that may be responsible for the
observed metastasis-associated metabolic alterations, suggested by gene
expression data. This was pursued using a combination of high-throughput liquid-
and gas-chromatography-based mass spectrometry (LC/MS and GC/MS) for a global
metabolic profiling/subtraction of four pairs of high/low metastatic OS cell
lines. By comparing the identity and level of the metabolites between high/low
metastatic cells, several metabolic pathways were identified to be differentially
activated, such as arginine, glutathione, inositol and fatty acid metabolic
pathways. To further interrogate these results, we investigated the effects of
inositol pathway dysregulation, through the exposure of metastatic OS cells to
IP6 (inositol hexaphosphate). Although IP6 exposures had modest to minimal
effects on cell proliferation, we observed reduced cellular glycolysis, down
regulation of PI3K/Akt signaling and suppression of OS metastatic progression.
Collectively these data supported further investigation of metabolic
sensitivities as anti-metastatic strategies in a clinical setting as well as
investigation of altered metabolomics associated with metastatic progression.
PMID- 28404950
TI - High expression of PTBP1 promote invasion of colorectal cancer by alternative
splicing of cortactin.
AB - Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of
mRNA regulation including alternative splicing metabolism during tumorigenesis
due to its RNA-binding activity. Initially, we found that high expressed PTBP1
and poor prognosis was interrelated in colorectal cancer (CRC) patients with
stages II and III CRC, which widely different in prognosis and treatment, by
immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In
our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation
and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal
cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many
target genes involving in tumorgenesis in colon cancer cells. We confirmed that
the splicing of cortactin exon 11 which was only contained in cortactin isoform
a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin
isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin
isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking
down cortactin isoform-a significantly decreased cell migration and invasion in
colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1
knockdown effect of cell motility. In summary the study revealed that PTBP1
facilitates colorectal cancer migration and invasion activities by inclusion of
cortactin exon 11.
PMID- 28404951
TI - Search for rare protein altering variants influencing susceptibility to multiple
myeloma.
AB - The genetic basis underlying the inherited risk of developing multiple myeloma
(MM) is largely unknown. To examine the impact of rare protein altering variants
on the risk of developing MM we analyzed high-coverage exome sequencing data on
513 MM cases and 1,569 healthy controls, performing both single variant and gene
burden tests. We did not identify any recurrent coding low-frequency alleles (1
5%) with moderate effect that were statistically associated with MM. In a gene
burden analysis we did however identify a promising relationship between
variation in the marrow kinetochore microtubule stromal gene KIF18A, which plays
a role in control mitotic chromosome positioning dynamics, and risk of MM (P
=3.6x10-6). Further analysis showed KIF18A displays a distinct pattern of
expression across molecular subgroups of MM as well as being associated with
patient survival. Our results inform future study design and provide a resource
for contextualizing the impact of candidate MM susceptibility genes.
PMID- 28404952
TI - High-throughput detection of clinically targetable alterations using next
generation sequencing.
AB - Next-generation sequencing (NGS) has revolutionized the therapeutic care of
patients by allowing high-throughput and parallel sequencing of large numbers of
genes in a single run. However, most of available commercialized cancer panels
target a large number of mutations that do not have direct therapeutic
implications and that are not fully adapted to low quality formalin-fixed,
paraffin-embedded (FFPE) samples. Here, we designed an amplicon-based NGS panel
assay of 16 currently actionable genes according to the most recent
recommendations of the French National Cancer Institute (NCI). We developed a
panel of short amplicons (<150 bp) using dual-strand library preparation. The
clinical validation of this panel was performed on well-characterized controls
and 140 routine diagnostic samples, including highly degraded and cross-linked
genomic DNA extracted from FFPE tumor samples. All mutations were detected with
elevated inter-laboratory and inter-run reproducibility. Importantly, we could
detect clinically actionable alterations in FFPE samples with variant allele
frequencies as low as 1%. In addition, the overall molecular diagnosis rate was
increased from 40.7% with conventional techniques to 59.2% with our NGS panel,
including 41 novel actionable alterations normally not explored by conventional
techniques. Taken together, we believe that this new actionable target panel
represents a relevant, highly scalable and robust tool that is easy to implement
and is fully adapted to daily clinical practice in hospital and academic
laboratories.
PMID- 28404953
TI - Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury
in rats.
AB - To study how hydrogen-rich saline (HS) promotes the recovery of testicular
biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a
right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats.
Animals were divided into four groups: normal group; vehicle group: sham-operated
rats administered saline; hSCI group: subjected to hSCI and administered saline;
HRST group: subjected to hSCI and administered HS. Hind limb neurological
function, testis index, testicular morphology, mean seminiferous tubular diameter
(MSTD) and seminiferous epithelial thickness (MSET), the expression of heme
oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1),
cell ultrastructure, and apoptosis of spermatogenic cells were studied. The
results indicated that hSCI significantly decreased the hind limb neurological
function, testis index, MSTD, and MSET, and induced severe testicular
morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were
overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis
of spermatogenic cells and the ultrastructural damage of cells in the hypophysis
and testis. After HS administration, all these parameters were considerably
improved, and the characteristics of hSCI testes were similar to those of normal
control testes. Taken together, HS administration can promote the recovery of
testicular biological function by anti-oxidative, anti-inflammatory, and anti
apoptotic action. More importantly, HS can inhibit the hSCI-induced
ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of
the hypothalamic-pituitary-testis axis, and thereby promote the recovery of
testicular injury. HS administration also inhibited the hSCI-induced
ultrastructural changes in testicular spermatogenic cells, Sertoli cells and
interstitial cells.
PMID- 28404954
TI - Upregulation of the long non-coding RNA PVT1 promotes esophageal squamous cell
carcinoma progression by acting as a molecular sponge of miR-203 and LASP1.
AB - Long non-coding RNAs are a group of non-coding RNAs longer than 200 nucleotides
and possess diverse functions and exhibit exquisite cell-specific and
developmental dynamic expression patterns. The role of the long non-coding RNA
PVT1 in esophageal squamous cell carcinoma remains unsolved. Here, we showed that
PVT1 expression is significantly up-regulated in ESCC tumor samples compared with
their normal counterparts. Knockdown of PVT1 suppressed tumor growth in vitro and
in vivo. Further studies revealed that silence of PVT1 lead to up-regulation of
miR-203, and vice versa. Moreover, LASP1 was found to be downregulated after
knockdown of PVT1 and overexpression of LASP1 attenuated the tumor-suppressive
roles of PVT1 knockdown. Our results suggest that PVT1 promote ESCC progression
via functioning as a molecular sponge for miR-203 and LASP1 and provide the first
evidence of dysregulated PVT1/miR-203/LASP1 axis in ESCC.
PMID- 28404955
TI - Identification of skin-related lncRNAs as potential biomarkers that involved in
Wnt pathways in keloids.
AB - The long non-coding RNAs (lncRNAs) regulating encoding transcripts/genes involved
in Wnt signalling pathway in keloids is largely unclear. We used a pathway
focused lncRNA microarray to detect the differentiated expression profiles of
both lncRNAs and genes involved in Wnt pathway, thus a total of 116 Wnt-targeted
genes and 69 Wnt-related lncRNAs aberrantly expressed in keloids were initially
identified. A stepwise bioinformatics was further performed to find skin-related
lncRNA/gene pairs in Wnt pathway in keloids. Firstly, an lncRNA/gene co
expression network with clustered functional modules was constructed;
simultaneously, 114 Wnt-genes regarding to dermis were online enriched using
Phenotype Enrichment. Secondly, 17 skin-related keloid-aberrant Wnt-genes were
acquired by overlapping the 114 skin-related Wnt-genes with the 116 keloid
aberrant Wnt-genes. Thirdly, after co-expression coefficient of each lncRNA/gene
profile being ranked respectively, 11 top co-expressed lncRNAs characterized with
the highest co-expression coefficients to the 17 genes were identified. Fourthly,
seven of the 11 top co-expressed lncRNAs exhibiting array-detected aberrant
expression in keloids, together with their 12 most interactive Wnt-genes, were
selected to undergo in-pair intracellularly quantitative PCR validation in
keloids. As a result, four lncRNAs including CACNA1G-AS1, HOXA11-AS, LINC00312
and RP11-91I11.1 with their six paired Wnt-genes undergoing both array-and-qPCR
as well as lncRNA-and-gene double validation were finally identified as skin
related lncRNA/gene pairs that involved in Wnt signalling pathway in keloids. In
conclusion, in-depth exploration on these easily-accessible lncRNAs in keloids
might aid to find the novel target on how to maintain highly recurrent tumours
benign via Wnt-involved network regulation.
PMID- 28404957
TI - Gene methylation as a powerful biomarker for detection and screening of non-small
cell lung cancer in blood.
AB - DNA methylation has been reported to become a potential powerful tool for cancer
detection and diagnosis. However, the possibilities for the application of blood
based gene methylation as a biomarker for non-small cell lung cancer (NSCLC)
detection and screening remain unclear. Hence, we performed this meta-analysis to
evaluate the value of gene methylation detected in blood samples as a noninvasive
biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control
studies. In the genes with more than three studies, we found that the methylation
of P16, RASSF1A, APC, RARbeta, DAPK, CDH13, and MGMT was significantly associated
with risks of NSCLC. The methylation statuses of P16, RASSF1A, APC, RARbeta,
DAPK, CDH13, and MGMT were not linked to age, gender, smoking behavior, and tumor
stage and histology in NSCLC. Therefore, the use of the methylation status of
P16, RASSF1A, APC, RARbeta, DAPK, CDH13, and MGMT could become a promising and
powerful biomarker for the detection and screening of NSCLC in blood in clinical
settings. Further large-scale studies with large sample sizes are necessary to
confirm our findings in the future.
PMID- 28404958
TI - Elevated FOXO6 expression correlates with progression and prognosis in gastric
cancer.
AB - : The FOXO6 correlated with tumor progression in a wide range of carcinomas, yet
little is known in gastric cancer. The expression of FOXO6 and matrix
metallopeptidase 9 (MMP-9) was assessed by immunohistochemistry in 192 gastric
carcinoma specimens. The correlation between FOXO6 expression with MMP-9,
clinicopathological/prognostic value in gastric cancer was examined. FOXO6
overexpression was significantly associated with depth of invasion, lymph node
metastasis and stage of disease. In univariate and multivariate analyses, FOXO6
was an independent prognostic factor for both overall survival (OS) and
recurrence-free survival (RFS). Moreover, FOXO6 over-expression was correlated
with poor prognosis in patients subgroups stratified by tumor size, depth of
invasion and lymph node metastasis. FOXO6 expression was increased in both
prominent serosal invasion group and lymph node metastasis group. In addition,
FOXO6 expression was positively correlated with MMP-9 among 192 gastric cancer
tissues. Patients with FOXO6 over-expression had poor OS and shorter RFS in low
and high invasiveness groups. Furthermore, stratified analysis showed that the
TNM stage I patients with high FOXO6 expression had poor prognosis than those
with low FOXO6 expression. In conclusion, FOXO6 overexpression promotes tumor
aggressiveness and prognosis, and could be a promising target for prognostic
prediction in gastric cancer patients. CONDENSED ABSTRACT: The aim of this study
was to analyze the role of FOXO6 in patients with gastric carcinoma. FOXO6 may
play an important role on tumor invasion, metastasis and prognosis. It may also
serve as a novel target for prognostic prediction.
PMID- 28404959
TI - Inhibition of the prolyl isomerase Pin1 enhances the ability of sorafenib to
induce cell death and inhibit tumor growth in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second
leading cause of cancer deaths, partially due to its heterogeneity and drug
resistance. Sorafenib is the only medical treatment with a proven efficacy
against advanced HCC, but its overall clinical efficacy is still modest.
Therefore, a major challenge is how to improve its therapeutic efficacy. The
unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably,
Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to
HCC tumorigenesis. However, the role of Pin1 in the efficacy of sorafenib against
HCC is unknown. Here we found that sorafenib down-regulated Pin1 mRNA and protein
expression, likely through inhibition of Pin1 transcription by the Rb/E2F
pathway. Importantly, Pin1 knockdown potently enhanced the ability of sorafenib
to induce cell death in HCC, which was further supported by the findings that
Pin1 knockdown led to stabilization of Fbxw7 and destabilization of Mcl-1.
Furthermore, all-trans retinoic acid (ATRA), a known anticancer drug that
inhibits and ultimately induces degradation of active Pin1 in cancer cells, also
potently sensitized HCC cells to sorafenib-induced cell death at least in part
through a caspase-dependent manner. Moreover, ATRA also synergistically enhanced
the ability of sorafenib to reduce Pin1 and inhibit tumor growth of HCC in mouse
xenograft models. Collectively, these results not only demonstrate that Pin1 down
regulation is a key event underlying the anti-tumor effects of sorafenib, but
also uncover that Pin1 inhibitors offer a novel approach to enhance the
therapeutic efficacy of sorafenib against HCC.
PMID- 28404960
TI - Impact of metformin on C-reactive protein levels in women with polycystic ovary
syndrome: a meta-analysis.
AB - The impact of the recommended first-line treatment with metformin on C-reactive
protein (CRP) levels in patients with polycystic ovary syndrome (PCOS) is still
controversial. We conducted a meta-analysis of studies reporting the impact of
metformin on serum CRP levels in women with PCOS. The weighted mean differences
(WMDs) and the corresponding 95% confidence intervals (CIs) were used to assesse
the effects. GRADE approach was used to assesse the quality of the evidence. A
total of 20 studies that included 433 women with PCOS were analyzed. CRP levels
significantly decreased after metformin treatment (WMD = -1.23mg/L, 95%CI: -1.65
to -0.81, I2 = 93% and P < 0.001 for heterogeneity). The decreased levels of CRP
were observed both in lean (BMI<25 kg/m2) and obese (BMI>25 kg/m2) patients.
Interestingly, the degree of decreased CRP levels was not depended on metformin
dosage, but more significantly in patients treated beyond 6 months (WMD>=6months
= -1.47mg/L vs. WMD<6months = -0.94 mg/L). Decreased CRP levels are not
associated with the status of IR and androgen in patients with PCOS. However, the
quality of evidence was very low because of the limitations and inconsistency of
the included studies. Therefore, metformin shows the potential effects on CRP
levels in women with PCOS. However, considering the very low quality of evidence
for the analysis, the effect of metformin on CRP levels are still very uncertain,
and large-scale randomized-controlled study is needed to ascertain the long-term
effects of metformin in PCOS.
PMID- 28404961
TI - Increased platelet-lymphocyte ratio closely relates to inferior clinical features
and worse long-term survival in both resected and metastatic colorectal cancer:
an updated systematic review and meta-analysis of 24 studies.
AB - Colorectal cancer (CRC) is one of the most common cancers worldwide. However, the
prognostic and clinical value of platelet-lymphocyte ratio (PLR) in colorectal
cancer was still unclear, which attracted more and more researchers' considerable
attention. We performed a systematic review and meta-analysis to investigate the
relationship between PLR and survival as well as clinical features of CRC update
to September 2016. The hazard ratio (HR) or odds ratio (OR) with 95% confidence
interval (CI) were calculated to access the association. We included 24 eligible
studies with a total of 13719 patients. Elevated PLR predicted shorter overall
survival (OS) (HR=1.47; 95%CI, 1.28-1.68; p<0.001), poorer disease-free survival
(DFS) (HR=1.51; 95% CI, 1.2-1.91; p=0.001), and worse recurrence-free survival
(RFS) (HR=1.39; 95% CI, 1.03-1.86; p=0.03), but had nothing to do with Cancer
specific survival (CSS) (HR=1.14; 95% CI, 0.92-1.42; p=0.223). After trim and
fill method, the connection between PLR and DFS disappeared (HR=1.143; 95%CI,
0.903-1.447; p=0.267). By subgroup analyze, we found that increased PLR
predicated a worse OS and DFS in patients who underwent surgery, and this
prognostic role also shown both in metastatic and nonmetastatic patients. In
addition, elevated PLR was associated with poorly differentiated tumor (OR=1.51;
95% CI, 1.26-1.81; p<0.001), higher tumor stage (OR=1.25; 95% CI, 1.05-1.49;
p=0.012), lymphovascular invasion (LVI) (OR=1.25; 95% CI, 1.09-1.43; p=0.001),
and the recurrence of CRC (OR=2.78; 95% CI, 1.36-5.68; p=0.005). We indicated
that pretreatment PLR was a good prognostic marker for CRC patients. High PLR was
related to worse OS, RFS and poor clinical characteristics.
PMID- 28404962
TI - Genetic variations of TLR5 gene interacted with Helicobacter pylori infection
among carcinogenesis of gastric cancer.
AB - Gastric cancer (GC) ranks the second prevalent cancer type and the second cancer
related death in China. However, the precise mechanisms of GC development remain
poorly understood. Chronic infection with Helicobacter pylori is the strongest
identified risk factor for GC. Toll-like receptor (TLR) genes, which play
critical roles in Helicobacter pylori induced chronic inflammation, may also be
implicated in GC susceptibility. TLR5 signaling deficiency could deregulate a
cascade of inflammatory events. In current study, we systematically evaluated
genetic variations of TLR5, and their interaction with Helicobacter pylori
infection among carcinogenesis of gastric cancer, using a large case-controls
study among Chinese population. Minor alleles of three SNPS, including rs5744174
(P = 0.001), rs1640827 (P = 0.005), and rs17163737 (P = 0.004), were
significantly associated with increased GC risk (OR ranged from 1.20-1.24).
Significant interactions with Helicobacter pylori infection were also identified
for rs1640827 (P for interaction = 0.009) and rs17163737 (P for interaction =
0.006). These findings suggest that genetic variants in TLR5 may modify the role
of Helicobacter pylori infection in the process of causing GC.
PMID- 28404963
TI - Tumor SOCS3 methylation status predicts the treatment response to TACE and
prognosis in HCC patients.
AB - BACKGROUND: Suppressor of cytokine signaling (SOCS) 1 and 3 methylation have been
associated with clinical features and outcomes of cancer patients. However, their
roles in determining the treatment response to transarterial chemoembolization
(TACE) in patients with hepatocellular carcinoma (HCC) remain unknown. RESULTS:
We found that presence of SOCS3 methylation is significantly associated with the
major clinical features of HCC patients, including tumor stage, lymph node and
vascular invasion. Of note, we observed that the presence of SOCS3 methylation is
closely related to TACE response. In prognosis analyses, HCC patients with SOCS3
methylation presence have a poorer prognosis indicated by lower 3-, and 5-year
survival rates and shorter mean survival period, than those without. Multivariate
COX analysis confirms the prognostic role of the presence of SOCS3 methylation in
HCC patients receiving TACE treatment. MATERIALS AND METHODS: A total of 246 HCC
patients receiving TACE were enrolled in this study. Tumor samples was obtained
from echo-guided fine needle aspiration and genomic DNA from tumor samples was
purified. SOCS1 and SOCS3 methylation status were detected using methylation
specific polymerase chain reaction. The treatment responses to TACE of patients
were evaluated after procedure and all patients were followed for prognosis
analysis. CONCLUSIONS: This finding suggests that the presence of SOCS3
methylation is a marker to predict treatment response and prognosis in HCC
patients receiving TACE therapy.
PMID- 28404964
TI - Identification of serum miR-139-3p as a non-invasive biomarker for colorectal
cancer.
AB - Aberrant levels of circulating microRNAs are potential biomarkers for the early
detection of colorectal cancer. The aim of this study was to study miR-139-3p and
miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We
applied quantitative polymerase chain reaction to determine the levels of miR-139
3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum
samples of 117 patients and 90 control subjects. Our results showed that miR-139
3p was silenced whereas miR-622 was overexpressed in colorectal cancer.
Similarly, serum miR-139-3p level was significantly lower in colorectal cancer
patients than in control subjects whereas miR-622 was more frequently detectable
in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a
sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high
sensitivity and specificity for both early and late stage CRCs and proximal and
distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and
specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped
for late stage patients (72.7%). We also included analyses of the blood CEA level
for comparing the diagnostic performance of these blood-based biomarkers. The
median level in CRC patients (3.6 ng/ml) was significantly higher than that in
control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515.
CEA showed a positive correlation with tumor stage and age of patients and its
level was higher in male. Collectively, serum miR-139-3p has strong potential as
a promising non-invasive biomarker in colorectal cancer detection.
PMID- 28404965
TI - Impact of statins therapy on morphological changes in lipid-rich plaques
stratified by 10-Year framingham risk score: A serial optical coherence
tomography study.
AB - The aim of the study was to investigate the impact of statins therapy on
morphological changes of lipid-rich plaques by OCT (optical coherence tomography)
in patients with known CHD (coronary heart disease), stratified by FRS. Ninety
seven lipid-rich plaques from sixty-nine patients who received statins therapy
and underwent serial OCT images (baseline, 6-month and 12-month) were divided
into 2 groups according to the FRS (framingham risk score): low risk group A
(FRS<10%, N=35, n=45), moderate to high risk group B (FRS>=10%, N=34, n=52).
Fibrous cap thickness (FCT) was measured at its thinnest part 3 times. Baseline
characteristics were not different between the 2 groups. FCT sustained increased
from baseline to 6-month and 12-month follow up in both group A (59.8+/-20.4MUm,
118.3+/-62.5MUm, and 158.8+/-83.4MUm respectively, P<0.001) and group B (62.2+/
16.8MUm, 125.1+/-78.7MUm, 163.8+/-75.5MUm respectively, P<0.001). Lipid index was
significantly decreased in both group A (1862.1+/-1164.5, 1530.3+/-1108.7,
1322.9+/-1080.4, P<0.001) and group B (1646.6+/-958.5, 1535.1+/-1049.1, 1258.6+/
1045, P=0.016). The incidence of TCFA was decreased statistically in both group A
(P <0.001) and group B (P <0.001). The patients with known CHD can equivalently
benefit from statins therapy by stabilizing the lipid-rich plaques. Patients with
moderate to high FRS might benefit more within the first year from event time.
PMID- 28404966
TI - A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid
cancer.
AB - The bispecific antibody is a novel antibody, which can target two different
antigens and mediate specific killing effects by selectively redirecting effector
cells to the target cells. Here, we designed and synthesized a bispecific
antibody (BsAb) that can bind cellular-mesenchymal to epithelial transition
factor (c-MET, overexpressed in several human solid tumor), and programmed death
1 (PD-1, involved in cancer cell immune evasion) with high affinity and
specificity. We found that BsAb can induce the degradation of c-MET protein in
cancer cells, including MKN45, a gastric cancer cell line, and A549, a lung
cancer cell line. BsAb inhibited hepatocyte growth factor (HGF)-mediated
proliferation, migration, and antiapoptosis, and downregulated HGF-stimulated
phosphorylation of c-MET, protein kinase B (AKT), and extracellular signal
regulated kinase (ERK1/2). BsAb can also rescue T cell activation. Furthermore,
xenograft analysis revealed that BsAb markedly inhibits the growth of
subcutaneously implanted tumors and chronic inflammation. On the basis of these
results, we have identified a potential bispecific drug, which can effectively
target c-MET and PD-1 for the treatment of human solid cancers.
PMID- 28404968
TI - Loss of nuclear BAP1 expression is associated with poor prognosis in oral mucosal
melanoma.
AB - Oral mucosal melanoma (OMM) is an aggressive neoplasm with an extremely poor
prognosis. BAP1 is a tumor suppressor that has been associated with the outcome
of melanomas and other malignancies. In this study, we investigated the genetic
alterations in BAP1 and the prognostic potential of BAP1 protein expression in
oral mucosal melanoma. DNA sequence analysis of BAP1 from 12 OMM patient samples
revealed missense mutations in the tissues from four patients. Based on
immunohistochemical staining, loss of nuclear BAP1 expression was associated with
poor overall survival (P < 0.001, Log-rank = 21.308) and distant metastasis (P =
0.034, OR = 0.320). Multivariate analysis showed BAP1 to be an independent
prognostic factor (P = 0.027, HR = 0.479). It thus appears that loss of nuclear
BAP1 expression is an independent prognostic factor of poor overall survival and
associated with distant metastasis in OMM.
PMID- 28404967
TI - GLI1-mediated regulation of side population is responsible for drug resistance in
gastric cancer.
AB - Gastric cancer is the third leading cause of cancer-related mortality worldwide.
Chemotherapy is frequently used for gastric cancer treatment. Most patients with
advanced gastric cancer eventually succumb to the disease despite some patients
responded initially to chemotherapy. Thus, identifying molecular mechanisms
responsible for cancer relapse following chemotherapy will help design new ways
to treat gastric cancer. In this study, we revealed that the residual cancer
cells following treatment with chemotherapeutic reagent cisplatin have elevated
expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog
signaling activation. We showed that GLI1 knockdown sensitized gastric cancer
cells to CDDP whereas ectopic GLI1 expression decreased the sensitivity. Further
analyses indicate elevated GLI1 expression is associated with an increase in
tumor sphere formation, side population and cell surface markers for putative
cancer stem cells. We have evidence to support that GLI1 is critical for
maintenance of putative cancer stem cells through direct regulation of ABCG2. In
fact, GLI1 protein was shown to be associated with the promoter fragment of ABCG2
through a Gli-binding consensus site in gastric cancer cells. Disruption of ABCG2
function, through ectopic expression of an ABCG2 dominant negative construct or a
specific ABCG2 inhibitor, increased drug sensitivity of cancer cells both in
culture and in mice. The relevance of our studies to gastric cancer patient care
is reflected by our discovery that high ABCG2 expression was associated with poor
survival in the gastric cancer patients who underwent chemotherapy. Taken
together, we have identified a molecular mechanism by which gastric cancer cells
gain chemotherapy resistance.
PMID- 28404970
TI - Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by
increasing its cognate gene PHB expression.
AB - Natural antisense transcripts (NATs) as one of the most diverse classes of long
noncoding RNAs (lncRNAs), have been demonstrated involved in fundamental
biological processes in human. Here, we reported that human prohibitin gene
pseudogene 1 (PHBP1) was upregulated in ESCC, and increased PHBP1 expression in
ESCC was associated with clinical advanced stage. Functional experiments showed
that PHBP1 knockdown inhibited ESCC cells proliferation, colony formation and
xenograft tumor growth in vitro and in vivo by causing cell-cycle arrest at the
G1-G0 phase. Mechanisms analysis revealed that PHBP1 transcript as an antisense
transcript of PHB is partially complementary to PHB mRNA and formed an RNA-RNA
hybrid with PHB, consequently inducing an increase of PHB expression at both the
mRNA and protein levels. Furthermore, PHBP1 expression is strongly correlated
with PHB expression in ESCC tissues. Collectively, this study elucidates an
important role of PHBP1 in promoting ESCC partly via increasing PHB expression.
PMID- 28404969
TI - Development of a radiosensitivity gene signature for patients with soft tissue
sarcoma.
AB - Adjuvant radiotherapy is an important clinical treatment option for the majority
of sarcomas. The motivation of current study is to identify a gene signature and
to predict radiosensitive patients who are most likely to benefit from
radiotherapy. Using the public available data of soft tissue sarcoma from The
Cancer Genome Atlas, we developed a cross-validation procedure for identifying a
gene signature and predicting radiosensitive patients through. The result showed
that the predicted radiosensitive patients who received radiotherapy had a
significantly better survival with a reduced rate of new tumor event and disease
progression. Strata analysis showed that the predicted radiosensitive patients
had significantly better survival under radiotherapy independent of histologic
types. A hierarchical cluster analysis was used to validate the gene signature,
and the results showed the predicted sensitivity for each patient well matched
the results from cluster analysis. Together, we demonstrate a radiosensitive
molecular signature that can be potentially used for identifying radiosensitive
patients with sarcoma.
PMID- 28404972
TI - Distribution patterns of 21-gene recurrence score in 980 Chinese estrogen
receptor-positive, HER2-negative early breast cancer patients.
AB - AIM: The current study aimed to explore the distribution patterns of 21-gene
recurrence score (RS) assay in Chinese early breast cancer patients. METHODS:
Nine hundred and eighty consecutive estrogen receptor(ER)-positive, human
epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients
treated at Ruijin Hospital, Shanghai Jiaotong University, School of Medicine from
2009 to 2016 were retrospectively recruited. Reverse transcriptase-polymerase
chain reaction (RT-PCR) assay of 21 genes were conducted in paraffin-embedded
tumor tissue to calculate the RS. Co-relations of RS and clinico-pathologic
factors were evaluated. Concordances of RT-PCR and immunohistochemistry (IHC)
tests were measured. Logistic regression were applied to determine independent
variables associated with RS. RESULTS: The median RS of 980 patients was
23(0~90), and the proportions of patients categorized as having a low,
intermediate, or high risk were 26.1%, 49.3% and 24.6%. The distribution of RS
varied significantly according to different tumor grade, T stage, progesterone
receptor(PR) status, Ki67 index and molecular subtypes (p<0.05). Grade, PR status
and Ki67 index were identified as independent variables associated with RS. The
concordance rates between RT-PCR and IHC test were 98.8% and 88.3% for ER and PR
status, and there were weak to moderate correlation between IHC and RT-PCR tests
for ER, PR expression and Ki67 index. CONCLUSIONS: RS correlated significantly
with grade, T stage, PR status, Ki67 index and molecular subtypes in Chinese
early breast cancer patients. Grade, PR status and Ki67 index could independently
predict RS. ER, PR status and Ki67 index between RT-PCR and IHC test had
remarkable concordance.
PMID- 28404971
TI - Association between tumor architecture derived from generalized Q-space MRI and
survival in glioblastoma.
AB - : While it is recognized that the overall resistance of glioblastoma to treatment
may be related to intra-tumor patterns of structural heterogeneity, imaging
methods to assess such patterns remain rudimentary. METHODS: We utilized a
generalized Q-space imaging (GQI) algorithm to analyze magnetic resonance imaging
(MRI) derived from a rodent model of glioblastoma and 2 clinical datasets to
correlate GQI, histology, and survival. RESULTS: In a rodent glioblastoma model,
GQI demonstrated a poorly coherent core region, consisting of diffusion tracts <5
mm, surrounded by a shell of highly coherent diffusion tracts, 6-25 mm.
Histologically, the core region possessed a high degree of necrosis, whereas the
shell consisted of organized sheets of anaplastic cells with elevated mitotic
index. These attributes define tumor architecture as the macroscopic organization
of variably aligned tumor cells. Applied to MRI data from The Cancer Imaging
Atlas (TCGA), the core-shell diffusion tract-length ratio (c/s ratio) correlated
linearly with necrosis, which, in turn, was inversely associated with survival (p
= 0.00002). We confirmed in an independent cohort of patients (n = 62) that the
c/s ratio correlated inversely with survival (p = 0.0004). CONCLUSIONS: The
analysis of MR images by GQI affords insight into tumor architectural patterns in
glioblastoma that correlate with biological heterogeneity and clinical outcome.
PMID- 28404973
TI - A phase II prospective study of the "Sandwich" protocol, L-asparaginase,
cisplatin, dexamethasone and etoposide chemotherapy combined with concurrent
radiation and cisplatin, in newly diagnosed, I/II stage, nasal type, extranodal
natural killer/T-cell lymphoma.
AB - Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas
with geographic and racial specificity. Up to now, the standard first-line
treatment is still not unified. In our previous report, the "sandwich" protocol
produced good results. Continuing to use the "sandwich" mode, a new chemotherapy
composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus
concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly
diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled.
Overall response rate was 86.4% including 83.3% complete response and 3.0%
partial remission. With the median follow-up of 23.5 months, 3-year overall
survival and 3-year progression-free survival were 70.1% and 67.4%, respectively.
The survival rate in stage II and extra-cavity stage I was significantly less
than that in limited stage I (p < 0.05). Therefore, we thought that the
"sandwich" mode was worthy of being generalized and LVDP combined with CCRT was
an effective protocol for I/II stage ENKTCL. But this regimen was not suitable
for all stage I/II patients and warrants larger sample and layering
investigation. This study was a registered clinical trial with number ChiCTR-TNC
12002353.
PMID- 28404977
TI - Assessment of the cancer risk factors of solitary pulmonary nodules.
AB - There are no large samples or exact prediction models for assessing the cancer
risk factors of solitary pulmonary nodules (SPNs) in the Chinese population. We
retrospectively analyzed the clinical and imaging data of patients with SPNs who
underwent computer tomography guided needle biopsy in our hospital from Jan 1st
of 2011 to March 30th of 2016. These patients were divided into a development
data set and a validation data set. These groups included 1078 and 344 patients,
respectively. A prediction model was developed from the development data set and
was validated with the validation data set using logistic regression. The
predictors of cancer in our model included female gender, age, pack-years of
smoking, a previous history of malignancy, nodule size, lobulated and spiculated
edges, lobulation alone and spiculation alone. The Area Under the Curves,
sensitivity and specificity of our model in the development and validation data
sets were significantly higher than those of the Mayo model and VA model (p <
0.001). We established the largest sampling risk prediction model of SPNs in a
Chinese cohort. This model is particularly applicable to SPNs > 8 mm in size.
SPNs in female patients, as well as SPNs featuring a combination of lobulated and
spiculated edges or lobulated edges alone, should be evaluated carefully due to
the probability that they are malignant.
PMID- 28404976
TI - Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen
receptor-beta.
AB - Epidemiological data demonstrated that hormone replace treatment has protective
effect against colorectal cancer (CRC). Our previous studies showed that this
effect may be associated with DNA mismatch repair. This study aims to investigate
the mechanism of estrogen induction of MLH1, and whether colorectal tumor
proliferation can be inhibited through induction of MLH1 by estrogen signal
pathway. Human CRC cell lines were used to examine the regulation of MLH1
expression by over-expression and depletion of estrogen receptor-alpha (ERalpha)
and estrogen receptor-beta (ERbeta), under the treatment with 17beta-estradiol or
beta-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and
Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation
assays were used to identify the estrogen response elements in the proximal
promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor
growth were determined in vitro and in vivo. We found that mismatch repair
ability and microsatellite stability of cells were enhanced by estrogen via
induction of MLH1 expression, which was mediated by ERbeta, through a
transcriptional activation process. Furthermore, we identified that ERbeta
exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo,
combined with 5-FU, through up-regulation of MLH1 expression. Finally, we
concluded that estrogen enhances mismatch repair ability and tumor inhibition
effect in vitro and in vivo, via induction of MLH1 expression mediated by ERbeta.
PMID- 28404978
TI - Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human
glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway.
AB - We investigated the effects of aquaporin 5 (AQP5) gene silencing on the
proliferation, migration and apoptosis of human glioma cells through regulating
the EGFR/ERK/p38MAPK signaling pathway. qRT-PCR was applied to examine the mRNA
expressions of AQP5 in five human glioma cell lines. U87-MG, U251 and LN229 cells
were selected and assigned into blank, vector, AQP5 siRNA and FlagAQP5 groups.
MTT assay was used to measure cell proliferation. Flow cytometry (FCM) with
AnnexinV-FITC/PI double staining and PI staining were employed to analyze cell
apoptosis and cell cycle respectively. Scratch test was used to detect cell
migration. Western blotting was performed to determine the EGFR/ERK/p38 MAPK
signaling pathway-related proteins. Results showed that the positive expression
of AQP5 in primary glioblastoma was associated with the tumor size and whether
complete excision was performed. The mRNA expressions of AQP5 in cell lines of
U87-MG, U251 and LN229 were significantly higher than in U373 and T98G. The
proliferation rates of U87-MG, U251 and LN229 cells in the AQP5 siRNA group were
lower than in the vector and blank groups. The apoptosis rate increased in the
AQP5 siRNA group compared with the vector group. Scratch test demonstrated that
AQP5 gene silencing could suppress cell migration. Compared with the vector and
blank groups, the AQP5 siRNA group showed decreased expressions of the ERK1/2,
p38 MAPK, p-ERK1/2 and p-p38 MAPK proteins. AQP5 gene silencing could inhibit the
cell proliferation, reduce cell migration and promote the cell apoptosis of U87
MG, U251 and LN229 by suppressing EGFR/ERK/p38 MAPK signaling pathway.
PMID- 28404974
TI - Tumor immunotherapy: drug-induced neoantigens (xenogenization) and immune
checkpoint inhibitors.
AB - More than 40 years ago, we discovered that novel transplantation antigens can be
induced in vivo or in vitro by treating murine leukemia with dacarbazine. Years
later, this phenomenon that we called "Chemical Xenogenization" (CX) and more
recently, "Drug-Induced Xenogenization" (DIX), was reproduced by Thierry Boon
with a mutagenic/carcinogenic compound (i.e. N-methyl-N'-nitro-N
nitrosoguanidine). In both cases, the molecular bases of DIX rely on mutagenesis
induced by methyl adducts to oxygen-6 of DNA guanine. In the present review we
illustrate the main DIX-related immune-pharmacodynamic properties of triazene
compounds of clinical use (i.e. dacarbazine and temozolomide).In recent years,
tumor immunotherapy has come back to the stage with the discovery of immune
checkpoint inhibitors (ICpI) that show an extraordinary immune-enhancing
activity. Here we illustrate the salient biochemical features of some of the most
interesting ICpI and the up-to-day status of their clinical use. Moreover, we
illustrate the literature showing the direct relationship between somatic
mutation burden and susceptibility of cancer cells to host's immune
responses.When DIX was discovered, we were not able to satisfactorily exploit the
possible presence of triazene-induced neoantigens in malignant cells since no
device was available to adequately enhance host's immune responses in clinical
settings. Today, ICpI show unprecedented efficacy in terms of survival times,
especially when elevated mutation load is associated with cancer cells.
Therefore, in the future, mutation-dependent neoantigens obtained by appropriate
pharmacological intervention appear to disclose a novel approach for enhancing
the therapeutic efficacy of ICpI in cancer patients.
PMID- 28404979
TI - In-vivo relation between plasma concentration of sorafenib and its safety in
Chinese patients with metastatic renal cell carcinoma: a single-center clinical
study.
AB - This single-center, observational study analyzed the association between plasma
concentration of sorafenib and its safety and efficacy in Chinese patients with
metastatic renal cell carcinoma (mRCC). Adult patients with RCC (n = 94), treated
with sorafenib were enrolled between January 2014 and January 2015. Sorafenib
plasma concentrations were measured by liquid chromatography-tandem mass
spectrometry. Safety and efficacy variables were evaluated using National Cancer
Institute-Common Toxicity Criteria for Adverse Events and Response Evaluation
Criteria in Solid Tumors criteria. Association of plasma concentration with
safety and efficacy was analyzed. The steady state plasma concentration of
sorafenib after 2 weeks of treatment ranged from 881 to 12,526 ng/mL. Major
adverse reactions (ADRs) included diarrhea (76.5%), hand-foot syndrome (HFS;
68.99%) and fatigue (55.32%). Significant association was reported between plasma
concentration and all the ADRs except rash. At 6 weeks, complete response (CR),
partial response (PR), stable disease (SD) and progressive disease (PD) was
reported in 3.1%, 13.82%, 52.2% and 13.82% patients, respectively. Objective
response and disease control rates were 17.02% and 69.14%. Plasma concentration
of sorafenib was >10,000 ng/mL in patients with severe ADRs, which decreased with
reduction in dose or discontinuation of treatment. After 21.2 weeks follow-up,
median progression free survival was 12.3 months. CR, PR, SD and PD were reported
in 1%, 46%, 33% and 19% patients. In conclusion, plasma concentration of
sorafenib was associated with its safety and efficacy in Chinese patients with
mRCC.
PMID- 28404980
TI - HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated
neurocognitive disorder.
AB - During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory
amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated
levels of extracellular glutamate and, in turn, neuronal apoptosis. We used
immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate
the molecular mechanisms underlying the decreased EAAT-2 expression during HAND
at the tissue and cellular levels. We used simian immunodeficiency virus-human
immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo
model of HAND. Our results show that EAAT-2 expression was decreased in the
cerebral cortex, while AEG-1 expression was increased, and the expression levels
of these proteins were negatively correlated. In vitro analyses showed that HIV-1
Tat inhibited EAAT-2 expression by inducing overexpression of AEG-1. More
specifically, HIV-1 Tat increased AEG-1 expression via the PI3-K signaling
pathway, while increasing EAAT-2 inhibition by YinYan-1 (YY-1) via the NF-kappaB
signaling pathway. These results warrant testing AEG-1 as a potential therapeutic
target for treating HAND.
PMID- 28404982
TI - A microcantilever-based silver ion sensor using DNA-functionalized gold
nanoparticles as a mass amplifier.
AB - Silver ions have been used to sterilize many products, however, it has recently
been demonstrated that silver ions can be toxic. This toxicity has been studied
over many years with the lethal concentration at 10 MUM. Silver ions can
accumulate through the food chain, causing serious health problems in many
species. Hence, there is a need for a commercially available silver ion sensor,
with high detection sensitivity. In this work, we develop an ultra-sensitive
silver ion sensor platform, using cytosine based DNA and gold nanoparticles as
the mass amplifier. We achieve a lower detection limit for silver ions of 10 pM;
this detection limit is one million times lower than the toxic concentration.
Using our sensor platform we examine highly selective characteristics of other
typical ions in water from natural sources. Furthermore, our sensor platform is
able to detect silver ions in a real practical sample of commercially available
drinking water. Our sensor platform, which we have termed a 'MAIS' (mass
amplifier ion sensor), with a simple detection procedure, high sensitivity,
selectivity and real practical applicability has shown potential as an early
toxicity assessment of silver ions in the environment.
PMID- 28404983
TI - Optimized Extraction, Preliminary Characterization, and In Vitro Antioxidant
Activity of Polysaccharides from Glycyrrhiza Uralensis Fisch.
AB - BACKGROUND This study performed optimized extraction, preliminary
characterization, and in vitro antioxidant activities of polysaccharides from
Glycyrrhiza uralensis Fisch. MATERIAL AND METHODS Three parameters (extraction
temperature, ratio of water to raw material, and extraction time) were optimized
for yields of G. uralensis polysaccharides (GUP) using response surface
methodology with Box-Behnken design (BBD). The GUP was purified using DEAE
cellulose 32-column chromatography. The main fraction obtained from G. uralensis
Fisch was GUP-II, which was composed of rhamnose, arabinose, galactose, and
glucose monosaccharide, was screened for antioxidant properties using DP Hand
hydroxyl radical scavenging assays. In addition, immunological activity of GUP-II
was determined by nitric oxide and lymphocyte proliferation assays. RESULTS
Optimization revealed maximum GUP yields with an extraction temperature of 99
degrees C, water: raw material ratio of 15: 1, and extraction duration of 2 h.
GUP-II purified from G. uralensis Fisch had good in vitro DPPH and hydroxyl
radical scavenging abilities. Immunologically, GUP-II significantly stimulated NO
production in RAW 264.7 macrophages, and significantly enhanced LPS-induced
lymphocyte proliferation. CONCLUSIONS Extraction of GUP from G. uralensis Fisch
can be optimized with respect to temperature, extraction period, and ratio of
water to material, using response surface methodology. The purified product (GUP
II) possesses excellent antioxidant and immunological activities.
PMID- 28404984
TI - Giant Iliopsoas Abscess Caused by Morganella Morganii.
AB - BACKGROUND While uncommon, iliopsoas abscesses can become the underlying cause of
a fever of unknown origin. Even in such cases, it is considered rare for an
iliopsoas abscess to extend into the subcutaneous space. CASE REPORT A 74-year
old woman with a history of schizophrenia was referred to our hospital with a
high-grade fever. The patient was unaware of her febrile status prior to
admission. There was no previous hospital admission. Examination revealed a non
tender mass in the lower right back that the patient had been aware of for
approximately 1 month. Initially, we considered a subcutaneous abscess; however,
computed tomography (CT) detected a large mass in the right retroperitoneum,
which extended into the adjacent subcutaneous space. Surgical drainage was
performed. M. morganii was detected in fluid evacuated from the abscess and in a
urine culture. Blood cultures were negative. A repeat enhanced CT revealed a
right renal abscess with staghorn calculus. This iliopsoas abscess was considered
to be due to a renal abscess. The combination of a minimally aggressive bacterial
species and the absence of disease awareness resulted in uncontrolled abscess
growth in this case. Surgical drainage and salvage nephrectomy was subsequently
performed, and she was discharged to a nursing home. CONCLUSIONS M. morganii can
lead to massive abscess formation without an underlying immunocompromised status.
Iliopsoas abscesses can surreptitiously extend into the subcutaneous space;
therefore, not all abscesses observable from the surface are necessarily
subcutaneous in origin.
PMID- 28404985
TI - Culture independent analysis using gnd as a target gene to assess Escherichia
coli diversity and community structure.
AB - Current culture methods to investigate changes in Escherichia coli community
structure are often slow and laborious. Genes such as gnd (6-phosphogluconate
dehydrogenase) have a highly variable nucleotide sequence and may provide a
target for E. coli microbiome analysis using culture-independent methods.
Metabarcoded PCR primers were used to generate separate libraries from calf
faecal samples for high throughput sequencing. Although a total of 348 separate
gnd sequence types (gSTs) were identified, 188 were likely to be due to
sequencing errors. Of the remaining 160 gSTs, 92 did not match those in a
database of 319 separate gnd sequences. 'Animal' was the main determinant of E.
coli diversity with limited impact of sample type or DNA extraction method on
intra-host E. coli community variation from faeces and recto-anal mucosal swab
samples. This culture-independent study has addressed the difficulties of
quantifying bacterial intra-species diversity and revealed that, whilst
individual animals may harbour >50 separate E. coli strains, communities are
dominated by <10 strains alongside a large pool of subdominant strains present at
low abundances. This method will be useful for characterising the diversity and
population structure of E. coli in experimental studies designed to assess the
impact of interventions on the gut microbiome.
PMID- 28404986
TI - Ecology of cold environments: new insights of bacterial metabolic adaptation
through an integrated genomic-phenomic approach.
AB - Cold environments dominate Earth's biosphere, hosting complex microbial
communities with the ability to thrive at low temperatures. However, the
underlying molecular mechanisms and the metabolic pathways involved in bacterial
cold-adaptation mechanisms are still not fully understood. Herein, we assessed
the metabolic features of the Antarctic bacterium Pseudoalteromonas haloplanktis
TAC125 (PhTAC125), a model organism for cold-adaptation, at both 4 degrees C and
15 degrees C, by integrating genomic and phenomic (high-throughput phenotyping)
data and comparing the obtained results to the taxonomically related Antarctic
bacterium Pseudoalteromonas sp. TB41 (PspTB41). Although the genome size of
PspTB41 is considerably larger than PhTAC125, the higher number of genes did not
reflect any higher metabolic versatility at 4 degrees C as compared to PhTAC125.
Remarkably, protein S-thiolation regulated by glutathione and
glutathionylspermidine appeared to be a new possible mechanism for cold
adaptation in PhTAC125. More in general, this study represents an example of how
'multi-omic' information might potentially contribute in filling the gap between
genotypic and phenotypic features related to cold-adaptation mechanisms in
bacteria.
PMID- 28404988
TI - Laser Frequency Noise in Coherent Optical Systems: Spectral Regimes and
Impairments.
AB - Coherent communication networks are based on the ability to use multiple
dimensions of the lightwave together with electrical domain compensation of
transmission impairments. Electrical-domain dispersion compensation (EDC)
provides many advantages such as network flexibility and enhanced fiber
nonlinearity tolerance, but makes the system more susceptible to laser frequency
noise (FN), e.g. to the local oscillator FN in systems with post-reception EDC.
Although this problem has been extensively studied, statistically, for links
assuming lasers with white-FN, many questions remain unanswered. Particularly,
the influence of a realistic non-white FN-spectrum due to e.g., the presence of
1/f-flicker and carrier induced noise remains elusive and a statistical analysis
becomes insufficient. Here we provide an experimentally validated theory for
coherent optical links with lasers having general non-white FN-spectrum and EDC.
The fundamental reason of the increased susceptibility is shown to be FN-induced
symbol displacement that causes timing jitter and/or inter/intra symbol
interference. We establish that different regimes of the laser FN-spectrum cause
a different set of impairments. The influence of the impairments due to some
regimes can be reduced by optimizing the corresponding mitigation algorithms,
while other regimes cause irretrievable impairments. Theoretical boundaries of
these regimes and corresponding criteria applicable to system/laser design are
provided.
PMID- 28404987
TI - Interleukin-33 regulates intestinal inflammation by modulating macrophages in
inflammatory bowel disease.
AB - Interleukin 33 (IL-33) that signals through the ST2 receptor has emerged as a
critical modulator in several inflammatory disorders, including inflammatory
bowel disease (IBD). However, the precise mechanisms by which IL-33 modulates IBD
are controversial. The aim of this study was thus to clarify the role of IL-33 in
IBD. The plasma levels of IL-33 were significantly decreased, but soluble ST2
levels were increased in patients with IBD compared to healthy individuals.
Moreover, IL-33 restored goblet cell numbers and induced macrophage switching
from the M1 to the M2 phenotype. These effects were sufficient to ameliorate
colitis in dextran sodium sulfate, trinitrobenzene sulfonic acid, and peritoneal
cavity cell transfer models. IL-33 facilitated goblet cell restoration via
modulating macrophages toward the M2 phenotype. In addition, wound healing was
significantly faster in IL-33-treated human monocyte-derived macrophages than in
control cells, which could be attributed to increased polarisation into M2
macrophages. We found that patients with IBD show decreased serum levels of IL-33
compared with healthy individuals and that IL-33 can attenuate colitis and aid
tissue repair in mice. The mechanism by which IL-33 exerts these effects appears
to involve the stimulation of differentiation of goblet cells and M2 macrophages.
PMID- 28404989
TI - Gyrator Based on Magneto-elastic Coupling at a Ferromagnetic/Piezoelectric
Interface.
AB - A gyrator is a non-reciprocal two port device with 180 degrees phase shift in
the transmissions between two ports. Though electromagnetic realizations of
gyrators have been well studied, devices based on other forms of interaction are
relatively unexplored. Here we demonstrate a device in which signal is
transmitted via magneto-elastic coupling, can function as a gyrator. The device
is built on a piezoelectric substrate: one port of this device has interdigital
transducers (IDTs) and the other port has a periodic array of nickel/gold lines.
When the magnetizations of Ni lines are excited into precession by magnetic field
generated by passing oscillating current through the gold lines, they emit
phonons in the form of surface acoustic waves (SAW) due to the magneto-elastic
coupling between Ni and substrate. The emitted SAW can be detected at the other
end by the IDTs. Conversely, when SAW is incident on Ni lines from IDTs, the
magnetization undergoes precession and can be inductively detected by Au lines.
The broken time reversal symmetry of the system due to the presence of
ferromagnet gives rise to the non-reciprocal transmission between the two ports.
These devices could function as novel building blocks for phonon based
information processing.
PMID- 28404990
TI - Aseismic transient during the 2010-2014 seismic swarm: evidence for longer
recurrence of M >= 6.5 earthquakes in the Pollino gap (Southern Italy)?
AB - In actively deforming regions, crustal deformation is accommodated by earthquakes
and through a variety of transient aseismic phenomena. Here, we study the 2010
2014 Pollino (Southern Italy) swarm sequence (main shock M W 5.1) located within
the Pollino seismic gap, by analysing the surface deformation derived from Global
Positioning System and Synthetic Aperture Radar data. Inversions of geodetic time
series show that a transient slip, with the same mechanism of the main shock,
started about 3-4 months before the main shock and lasted almost one year,
evolving through time with acceleration phases that correlate with the rate of
seismicity. The moment released by the transient slip is equivalent to M W 5.5,
significantly larger than the seismic moment release revealing therefore that a
significant fraction of the overall deformation is released aseismically. Our
findings suggest that crustal deformation in the Pollino gap is accommodated by
infrequent "large" earthquakes (M W >= 6.5) and by aseismic episodes releasing a
significant fraction of the accrued strain. Lower strain rates, relative to the
adjacent Southern Apennines, and a mixed seismic/aseismic strain release are in
favour of a longer recurrence for large magnitude earthquakes in the Pollino gap.
PMID- 28404992
TI - Impacts of alpine wetland degradation on the composition, diversity and trophic
structure of soil nematodes on the Qinghai-Tibetan Plateau.
AB - Alpine wetlands on the Qinghai-Tibetan Plateau are undergoing degradation.
However, little is known regarding the response of soil nematodes to this
degradation. We conducted investigations in a wet meadow (WM), a grassland meadow
(GM), a moderately degraded meadow (MDM) and a severely degraded meadow (SDM)
from April to October 2011. The nematode community taxonomic composition was
similar in the WM, GM and MDM and differed from that in the SDM. The abundance
declined significantly from the WM to the SDM. The taxonomic richness and Shannon
index were comparable between the WM and MDM but were significantly lower in the
SDM, and the Pielou evenness showed the opposite pattern. The composition,
abundance and diversity in the WM and SDM were relatively stable over time
compared with other habitats. The abundances of all trophic groups, aside from
predators, decreased with degradation. The relative abundances of herbivores,
bacterivores, predators and fungivores were stable, while those of omnivores and
algivores responded negatively to degradation. Changes in the nematode community
were mainly driven by plant species richness and soil available N. Our results
demonstrate that alpine wetland degradation significantly affects the soil
nematode communities, suppressing but not shifting the main energy pathways
through the soil nematode communities.
PMID- 28404991
TI - Intestinal PPARdelta protects against diet-induced obesity, insulin resistance
and dyslipidemia.
AB - Peroxisome proliferator-activated receptor delta (PPARdelta) is a ligand
activated transcription factor that has an important role in lipid metabolism.
Activation of PPARdelta stimulates fatty acid oxidation in adipose tissue and
skeletal muscle and improves dyslipidemia in mice and humans. PPARdelta is highly
expressed in the intestinal tract but its physiological function in this organ is
not known. Using mice with an intestinal epithelial cell-specific deletion of
PPARdelta, we show that intestinal PPARdelta protects against diet-induced
obesity, insulin resistance and dyslipidemia. Furthermore, absence of intestinal
PPARdelta abolished the ability of PPARdelta agonist GW501516 to increase plasma
levels of HDL-cholesterol. Together, our findings show that intestinal PPARdelta
is important in maintaining metabolic homeostasis and suggest that intestinal
specific activation of PPARdelta could be a therapeutic approach for treatment of
the metabolic syndrome and dyslipidemia, while avoiding systemic toxicity.
PMID- 28404993
TI - Impacts of Bisphenol A and Ethinyl Estradiol on Male and Female CD-1 Mouse
Spleen.
AB - The endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17alpha-ethinyl
estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite
ubiquitous human exposure to BPA, and the wide-spread clinical use of EE as oral
contraceptive adjuvant, the impact of these estrogenic endocrine disrupting
chemicals (EDCs) on the immune system is unclear. Here we report results of in
vivo dose response studies that analyzed the histology and microstructural
changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000
MUg/kg/day BPA or 0.02 to 2 MUg/kg/day EE from conception until 12-14 weeks of
age. Results of that analysis indicate that both BPA and EE have dose- and sex
specific impacts on the cellular and microanatomical structures of the spleens
that reveal minor alterations in immunomodulatory and hematopoietic functions.
These findings support previous studies demonstrating the murine immune system as
a sensitive target for estrogens, and that oral exposures to BPA and EE can have
estrogen-like immunomodulatory affects in both sexes.
PMID- 28404994
TI - Global analysis of glycoproteins identifies markers of endotoxin tolerant
monocytes and GPR84 as a modulator of TNFalpha expression.
AB - Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary
insensitivity to subsequent LPS challenges, a cellular state called endotoxin
tolerance. In this study, we investigated the LPS-induced global glycoprotein
expression changes of tolerant human monocytes and THP-1 cells to identify
markers and glycoprotein targets capable to modulate the immunosuppressive state.
Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein
expression changes during a 48 h LPS time course. The cellular snapshots at
different time points identified 1491 glycoproteins expressed by monocytes and
THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting
LPS-induced expression changes of secreted or membrane-anchored glycoproteins
derived from intracellular membrane coated organelles or from the plasma
membrane. Monocytes and THP-1 cells demonstrated marked differences in
glycoproteins differentially expressed in the tolerant state. Among the shared
differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was
identified as being capable of modulating pro-inflammatory TNFalpha mRNA
expression in the tolerant cell state when activated with its ligand Decanoic
acid.
PMID- 28404995
TI - Glucose uptake in Azotobacter vinelandii occurs through a GluP transporter that
is under the control of the CbrA/CbrB and Hfq-Crc systems.
AB - Azotobacter vinelandii, a strict aerobic, nitrogen fixing bacterium in the
Pseudomonadaceae family, exhibits a preferential use of acetate over glucose as a
carbon source. In this study, we show that GluP (Avin04150), annotated as an H+
coupled glucose-galactose symporter, is the glucose transporter in A. vinelandii.
This protein, which is widely distributed in bacteria and archaea, is uncommon in
Pseudomonas species. We found that expression of gluP was under catabolite
repression control thorugh the CbrA/CbrB and Crc/Hfq regulatory systems, which
were functionally conserved between A. vinelandii and Pseudomonas species. While
the histidine kinase CbrA was essential for glucose utilization, over-expression
of the Crc protein arrested cell growth when glucose was the sole carbon source.
Crc and Hfq proteins from either A. vinelandii or P. putida could form a stable
complex with an RNA A-rich Hfq-binding motif present in the leader region of gluP
mRNA. Moreover, in P. putida, the gluP A-rich Hfq-binding motif was functional
and promoted translational inhibition of a lacZ reporter gene. The fact that gluP
is not widely distributed in the Pseudomonas genus but is under control of the
CbrA/CbrB and Crc/Hfq systems demonstrates the relevance of these systems in
regulating metabolism in the Pseudomonadaceae family.
PMID- 28404996
TI - A rapid and non-invasive method for measuring the peak positive pressure of HIFU
fields by a laser beam.
AB - Based on the acousto-optic interaction, we propose a laser deflection method for
rapidly, non-invasively and quantitatively measuring the peak positive pressure
of HIFU fields. In the characterization of HIFU fields, the effect of nonlinear
propagation is considered. The relation between the laser deflection length and
the peak positive pressure is derived. Then the laser deflection method is
assessed by comparing it with the hydrophone method. The experimental results
show that the peak positive pressure measured by laser deflection method is
little higher than that obtained by the hydrophone, confirming that they are in
reasonable agreement. Considering that the peak pressure measured by hydrophones
is always underestimated, the laser deflection method is assumed to be more
accurate than the hydrophone method due to the absence of the errors in
hydrophone spatial-averaging measurement and the influence of waveform distortion
on hydrophone corrections. Moreover, noting that the Lorentz formula still
remains applicable to high-pressure environments, the laser deflection method
exhibits a great potential for measuring HIFU field under high-pressure
amplitude. Additionally, the laser deflection method provides a rapid way for
measuring the peak positive pressure, without the scan time, which is required by
the hydrophones.
PMID- 28404997
TI - Novel Fitc-Labeled Igy Antibody: Fluorescence Imaging Toxoplasma Gondii In Vitro.
AB - Toxoplasmosis is caused by T. gondii and can create serious health problems in
humans and also worldwide economic harm. Because of the clinical and veterinary
importance of toxoplasmosis, its timely and accurate diagnosis has a major impact
on disease-fighting strategies. T. gondii surface antigen 1 (SAG1), an
immunodominant-specific antigen, is often used as a diagnostic tool. Therefore,
the aim of this study was the optimization of novel fluorescein isothiocyanate
(FITC) labeling of the SAG1-specific IgY antibody to show the potential for
immunofluorescence imaging of T. gondii in vitro. The specificity of IgY
antibodies was controlled by an enzyme-linked immunosorbent assay (ELISA), and
the concentration of the IgY antibody was detected using a spectrophotometer. The
optimum incubation time and FITC concentration were determined with a
fluorescence spectrometer. The obtained FITC-labeled IgY was used for marking T.
gondii tachyzoites, which were cultured in vitro and viewed using light
microscopy. The interaction of the fluorescence-labeled antibody and the T.
gondii tachyzoites was examined with a fluorescence microscope. In this study,
for the first time, a FITC-labeled anti-SAG1 IgY antibody was developed according
to ELISA, fluorescence spectrometer, and fluorescence imaging of cell culture. In
the future, the obtained FITC-labeled T. gondii tachyzoites' specific IgY
antibodies may be used as diagnostic tools for the detection of T. gondii
infections in different samples.
PMID- 28404999
TI - Gout: Short telomeres in gout linked with flares and CVD.
PMID- 28404998
TI - A single biochemical activity underlies the pleiotropy of the aging-related
protein CLK-1.
AB - The Caenorhabditis elegans clk-1 gene and the orthologous mouse gene Mclk1 encode
a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone
(UQ). Mutations in these genes produce broadly pleiotropic phenotypes in both
species, including a lengthening of animal lifespan. A number of features of the
C. elegans clk-1 mutants, including a maternal effect, particularly extensive
pleiotropy, as well as unexplained differences between alleles have suggested
that CLK-1/MCLK1 might have additional functions besides that in UQ biosynthesis.
In addition, a recent study suggested that a cryptic nuclear localization signal
could lead to nuclear localization in cultured mammalian cell lines. Here, by
using immunohistochemical techniques in worms and purification techniques in
mammalian cells, we failed to detect any nuclear enrichment of the MCLK1 or CLK-1
proteins and any biological activity of a C. elegans CLK-1 protein devoid of a
mitochondrial localization sequence. In addition, and most importantly, by
pharmacologically restoring UQ biosynthesis in clk-1 null mutants we show that
loss of UQ biosynthesis is responsible for all phenotypes resulting from loss of
CLK-1, including behavioral phenotypes, altered expression of mitochondrial
quality control genes, and lifespan.
PMID- 28405000
TI - Osteoarthritis: Inflammation and fibrosis in adipose tissue of osteoarthritic
joints.
PMID- 28405002
TI - Development of New Carbon Resources: Production of Important Chemicals from Algal
Residue.
AB - Algal biomass has received attention as an alternative carbon resource owing not
only to its high oil production efficiency but also, unlike corn starch, to its
lack of demand in foods. However, algal residue is commonly discarded after the
abstraction of oil. The utilization of the residue to produce chemicals will
therefore increase the value of using algal biomass instead of fossil fuels.
Here, we report the use of algal residue as a new carbon resource to produce
important chemicals. The application of different homogeneous catalysts leads to
the selective production of methyl levulinate or methyl lactate. These results
demonstrate the successful development of new carbon resources as a solution for
the depletion of fossil fuels.
PMID- 28405003
TI - Surpassing light-induced cell damage in vitro with novel cell culture media.
AB - Light is extensively used to study cells in real time (live cell imaging),
separate cells using fluorescence activated cell sorting (FACS) and control
cellular functions with light sensitive proteins (Optogenetics). However, photo
sensitive molecules inside cells and in standard cell culture media generate
toxic by-products that interfere with cellular functions and cell viability when
exposed to light. Here we show that primary cells from the rat central nervous
system respond differently to photo-toxicity, in that astrocytes and microglia
undergo morphological changes, while in developing neurons and oligodendrocyte
progenitor cells (OPCs) it induces cellular death. To prevent photo-toxicity and
to allow for long-term photo-stimulation without causing cellular damage, we
formulated new photo-inert media called MEMO and NEUMO, and an antioxidant rich
and serum free supplement called SOS. These new media reduced the detrimental
effects caused by light and allowed cells to endure up to twenty times more light
exposure without adverse effects, thus bypassing the optical constraints
previously limiting experiments.
PMID- 28405004
TI - Engineered P450 biocatalysts show improved activity and regio-promiscuity in
aromatic nitration.
AB - Nitroaromatics are among the most important and commonly used chemicals but their
production often suffers from multiple unsolved challenges. We have previously
described the development of biocatalytic nitration processes driven by an
engineered P450 TxtE fusion construct. Herein we report the creation of improved
nitration biocatalysts through constructing and characterizing fusion proteins of
TxtE with the reductase domain of CYP102A1 (P450BM3, BM3R). The majority of
constructs contained variable linker length while one was rationally designed for
optimizing protein-protein interactions. Detailed biochemical characterization
identified multiple active chimeras that showed improved nitration activity,
increased coupling efficiency and higher total turnover numbers compared with
TxtE. Substrate promiscuity of the most active chimera was further assessed with
a substrate library. Finally, a biocatalytic nitration process was developed to
nitrate 4-Me-DL-Trp. The production of both 4-Me-5-NO2-L-Trp and 4-Me-7-NO2-L-Trp
uncovered remarkable regio-promiscuity of nitration biocatalysts.
PMID- 28405001
TI - Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?
AB - Today, we are facing a new era of digitization in the health care system, and
with increased access to health care information has come a growing demand for
safe, cost-effective and easy to administer therapies. Dietary habits have a
crucial influence on human health, affecting an individual's risk for
hypertension, heart disease and stroke, as well as influencing the risk of
developing of cancer. Moreover, an individual's lifestyle choices can greatly
influence the progression and manifestation of chronic autoimmune rheumatic
diseases. In light of these effects, it makes sense that the search for
additional therapies to attenuate such diseases would include investigations into
lifestyle modifications. When considering the complex web of factors that
influence autoimmunity, it is not surprising to find that several dietary
elements are involved in disease progression or prevention. In this Review,
several common nutritional components of the human diet are presented, and the
evidence for their effects on rheumatic diseases is discussed.
PMID- 28405005
TI - Carbon-bearing silicate melt at deep mantle conditions.
AB - Knowledge about the incorporation and role of carbon in silicate magmas is
crucial for our understanding of the deep mantle processes. CO2 bearing silicate
melting and its relevance in the upper mantle regime have been extensively
explored. Here we report first-principles molecular dynamics simulations of
MgSiO3 melt containing carbon in three distinct oxidation states - CO2, CO, and C
at conditions relevant for the whole mantle. Our results show that at low
pressures up to 15 GPa, the carbon dioxide speciation is dominated by molecular
form and carbonate ions. At higher pressures, the dominant species are silicon
polyhedral bound carbonates, tetrahedral coordination, and polymerized di
carbonates. Our results also indicate that CO2 component remains soluble in the
melt at high pressures and the solution is nearly ideal. However, the elemental
carbon and CO components show clustering of carbon atoms in the melt at high
pressures, hinting towards possible exsolution of carbon from silicate melt at
reduced oxygen contents. Although carbon lowers the melt density, the effect is
modest at high pressures. Hence, it is likely that silicate melt above and below
the mantle transition zone, and atop the core-mantle boundary could efficiently
sequester significant amounts of carbon without being gravitationally unstable.
PMID- 28405007
TI - Rapid and accurate peripheral nerve imaging by multipoint Raman spectroscopy.
AB - Raman spectroscopy allows label-free, minimally invasive, and accurate detection
of peripheral nerves. However, the conventional Raman imaging technique is time
consuming when measuring a large area of a sample. Establishing a method for
rapidly acquiring spatial distribution of a bundle of peripheral nerve fibers is
an essential step for Raman spectroscopy towards application in clinical surgery.
Here we present a multipoint Raman spectroscopic technique for rapid peripheral
nerve imaging. In only 5 seconds, spectra at 32 points situated on ex vivo rat
peripheral nerve bundles and adjoining connective tissues were acquired.
Principal component regression and discriminant analysis of spectra revealed that
the sensitivity, specificity and accuracy for nerve detection were 85.8%, 96.0%,
and 90.8%, respectively. Of 158 peripheral nerves, 152 (96.2%) showed ratio of
the number of nerve-positive prediction points to the total measurement points
being 0.4 or larger, whereas 119 (99.2%) connective tissues among 120 showed
ratio smaller than 0.4. Based on the ratio and a bright-field image of the
sample, accurate visualization of peripheral nerves was implemented. The results
indicated that the multipoint Raman spectroscopic technique is capable of rapid
and accurate peripheral nerve imaging.
PMID- 28405009
TI - Physical inactivity: a risk factor and target for intervention in renal care.
PMID- 28405006
TI - The adjuvant value of Andrographis paniculata in metastatic esophageal cancer
treatment - from preclinical perspectives.
AB - Esophageal cancer (EC) is the fourth and sixth leading cause of cancer-related
deaths in China and United States, respectively. The dismal prognosis of EC is
mainly attributed to distant metastases, which may not be overcome by
chemotherapy alone. Hence, the use of alternative adjuvant treatments, such as
herbal medicines, for metastatic EC remains a great desire of patients. Our
previous study demonstrated the in vivo anti-tumor and in vitro anti-invasion
activities of Andrographis paniculata (AP) in esophageal cancer. In the present
study, the chemical constituents of absorbed AP components through human
intestinal Caco-2 cell monolayer were verified for the first time. The anti
migratory activities and suppressive effects on metastasis-related factors such
as HER2, MMP2, MMP9, TM4SF3, CXCR4 of the absorbed AP components were revealed in
esophageal cancer cells EC-109. The anti-tumor and anti-metastatic effects of AP
water extract (1600 mg/kg) were further confirmed in metastatic esophageal
xenograft-bearing mice. Besides, AP water extract acted synergistically with
cisplatin plus 5-fluorouracil on inhibiting tumor nodule growth (with combination
index <0.7). Meanwhile, chemotherapeutics-induced side-effects could also be
reduced by AP water extract. The present findings provide evidence on safety and
advantages of the combined use of AP with chemotherapeutics in pre-clinical
setting.
PMID- 28405008
TI - Targeted Enrichment and Sequencing of Recent Endosymbiont-Host Lateral Gene
Transfers.
AB - Lateral gene transfer (LGT) from microbial symbionts to invertebrate animals is
described at an increasing rate, particularly between Wolbachia endosymbionts and
their diverse invertebrate hosts. We sought to assess the use of a capture system
to cost-effectively sequence such LGT from the host genome. The sequencing depth
of Illumina paired end data obtained with a Wolbachia capture system correlated
well with that for an Illumina paired end data set used to detect LGT in
Wolbachia-depleted B. malayi (p-value: <2e-16). Using a sequencing depth
threshold of two or three standard deviations above the mean, 96.9% or 96.7% of
positions, respectively, are predicted in the same manner between the two
datasets, with 24.7% or 42.5% of the known 49.0 kbp of LGT sequence predicted
correctly, respectively. Prior qPCR results for nuwts showed similar correlations
for both datasets supporting our conclusion that oligonucleotide-based capture
methods can be used to obtain sequences from Wolbachia-host LGT. However, at
least 121 positions had a minority of the reads supporting the endosymbiont
reference base call using the capture data, illustrating that sequence reads from
endosymbiont-host LGTs can confound endosymbiont genome projects, erroneously
altering the called consensus genome, a problem that is irrespective to the
sequencing technology or platform.
PMID- 28405012
TI - Accumulation of evidence regarding home blood pressure during pregnancy is
necessary.
PMID- 28405010
TI - Toll-like receptor 7 deficiency protects apolipoprotein E-deficient mice from
diet-induced atherosclerosis.
AB - Toll-like receptor 7 (TLR7) mediates autoantigen and viral RNA-induced cytokine
production. Increased TLR7 expression in human atherosclerotic lesions suggests
its involvement in atherogenesis. Here we demonstrated TLR7 expression in
macrophages, smooth muscle cells (SMCs), and endothelial cells from mouse
atherosclerotic lesions. To test a direct participation of TLR7 in
atherosclerosis, we crossbred TLR7-deficient (Tlr7 -/-) mice with apolipoprotein
E-deficient (Apoe -/-) mice and produced Apoe -/- Tlr7 -/- and Apoe -/- Tlr7 +/+
littermates, followed by feeding them an atherogenic diet to produce
atherosclerosis. Compared to Apoe -/- Tlr7 +/+ mice, Apoe -/- Tlr7 -/- mice
showed reduced aortic arch and sinus lesion areas. Reduced atherosclerosis in
Apoe -/- Tlr7 -/- mice did not affect lesion macrophage-positive area and CD4+ T
cell number per lesion area, but reduced lesion expression of inflammatory
markers major histocompatibility complex-class II and IL6, lesion matrix
degrading proteases cathepsin S and matrix metalloproteinase-9, and systemic
serum amyloid A levels. TLR7 deficiency also reduced aortic arch SMC loss and
lesion intima and media cell apoptosis. However, TLR7 deficiency did not affect
aortic wall elastin fragmentation and collagen contents, or plasma lipoproteins.
Therefore, TLR7 contributes to atherogenesis in Apoe -/- mice by regulating
lesion and systemic inflammation. A TLR7 antagonist may mitigate atherosclerosis.
PMID- 28405011
TI - Plasticity within excitatory and inhibitory pathways of the vestibulo-spinal
circuitry guides changes in motor performance.
AB - Investigations of behaviors with well-characterized circuitry are required to
understand how the brain learns new motor skills and ensures existing behaviors
remain appropriately calibrated over time. Accordingly, here we recorded from
neurons within different sites of the vestibulo-spinal circuitry of behaving
macaque monkeys during temporally precise activation of vestibular afferents.
Behaviorally relevant patterns of vestibular nerve activation generated a rapid
and substantial decrease in the monosynaptic responses recorded at the first
central stage of processing from neurons receiving direct input from vestibular
afferents within minutes, as well as a decrease in the compensatory reflex
response that lasted up to 8 hours. In contrast, afferent responses to this same
stimulation remained constant, indicating that plasticity was not induced at the
level of the periphery but rather at the afferent-central neuron synapse.
Strikingly, the responses of neurons within indirect brainstem pathways also
remained constant, even though the efficacy of their central input was
significantly reduced. Taken together, our results show that rapid plasticity at
the first central stage of vestibulo-spinal pathways can guide changes in motor
performance, and that complementary plasticity on the same millisecond time scale
within inhibitory vestibular nuclei networks contributes to ensuring a relatively
robust behavioral output.
PMID- 28405013
TI - A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in
Oceanic populations.
AB - It has been suggested that a 'thrifty' genotype hypothesis can account for high
prevalence of obesity in the island populations of Oceania. A recent genome-wide
association study revealed that a missense variant, rs373863828-A (p.Arg457Gln),
of the CREBRF gene (encoding CREB3 regulatory factor) was associated with an
excessive increase in body mass index (BMI) in Samoans. In the present study, the
association of rs373863828-A with an increase in BMI was examined in four
Austronesian (AN)-speaking populations in Oceania. We found that rs373863828-A
was frequently observed (frequency of 0.15) in Tongans (Polynesians), and was
strongly associated with higher BMI (P=6.1 * 10-4). A single copy of the
rs373863828-A allele increased BMI by 3.09 kg m-2 after adjustment of age and
sex. No significant association was detected in the other three AN-speaking
populations (Melanesians and Micronesians) living in Solomon Islands. This was
probably due to the low allele frequency (0.02-0.06) of rs373863828-A as well as
small sample size. The rs373863828-A allele was not found in both AN-speaking and
non-AN-speaking Melanesians living in Papua New Guinea. Our results suggest that
rs373863828-A of CREBRF, a promising thrifty variant, arose in recent ancestors
of AN-speaking Polynesians.
PMID- 28405014
TI - Update of the GJB2/DFNB1 mutation spectrum in Russia: a founder Ingush mutation
del(GJB2-D13S175) is the most frequent among other large deletions.
AB - Although mutations in the GJB2 gene sequence make up the majority of variants
causing autosomal-recessive non-syndromic hearing loss, few large deletions have
been shown to contribute to DFNB1 deafness. Currently, genetic testing for DFNB1
hearing loss includes GJB2 sequencing and DFNB1 deletion analysis for two common
large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Here, we report
frequency in Russia, clinical significance and evolutionary origins of a 101 kb
deletion, del(GJB2-D13S175), recently identified by us. In multiethnic cohort of
1104 unrelated hearing loss patients with biallelic mutations at the DFNB1 locus,
the del(GJB2-D13S175) allele frequency of up to 0.5% (11/2208) was determined and
this allele was shown to be predominantly associated with profound sensorineural
hearing loss. Additionally, eight previously unpublished GJB2 mutations were
described in this study. All patients carrying del(GJB2-D13S175) were of the
Ingush ancestry. Among normal hearing individuals, del(GJB2-D13S175) was observed
in Russian Republic of Ingushetia with a carrier rate of ~1% (2/241). Analysis of
haplotypes associated with the deletion revealed a common founder in the
Ingushes, with age of the deletion being ~3000 years old. Since del(GJB2-D13S175)
was missed by standard methods of GJB2 analysis, del(GJB2-D13S175) detection has
been added to our routine testing strategy for DFNB1 hearing loss.
PMID- 28405015
TI - Moderate plasma dilution using artificial plasma expanders shifts the haemostatic
balance to hypercoagulation.
AB - Artificial plasma expanders (PEs) are widely used in modern transfusion medicine.
PEs do not contain components of the coagulation system, so their infusion in
large volumes causes haemodilution and affects haemostasis. However, the existing
information on this effect is contradictory. We studied the effect of the very
process of plasma dilution on coagulation and tested the hypothesis that moderate
dilution with a PE should accelerate clotting owing to a decrease in
concentration of coagulation inhibitors. The standard clotting times, a thrombin
generation test, and the spatial rate of clot growth (test of thrombodynamics)
were used to assess donor plasma diluted in vitro with various PEs. The pH value
and Ca+2 concentration were maintained strictly constant in all samples. The
effect of thrombin inhibitors on dilution-induced hypercoagulation was also
examined. It was shown that coagulation was enhanced in plasma diluted up to 2.0
2.5-fold with any PE. This enhancement was due to the dilution of coagulation
inhibitors in plasma. Their addition to plasma or PE could partially prevent the
hypercoagulation shift.
PMID- 28405016
TI - Influenza-induced lung Trm: not all memories last forever.
AB - In the light of new findings that lung tissue resident memory CD8+ T cells (Trm)
represent major mediators of heterosubtypic immunity against influenza virus, it
is of utmost importance to understand the basic biological mechanisms behind
induction, formation and maintenance of this cell population. Addressing these
important knowledge gaps will potentially inform development of superior, broadly
protective influenza vaccines and new immunization strategies.
PMID- 28405017
TI - Lectin pathway factors in patients suffering from juvenile idiopathic arthritis.
AB - Both complement activation and certain infections (including those with Yersinia
sp.) may contribute to the pathogenesis of juvenile idiopathic arthritis (JIA).
We investigated factors specific for the lectin pathway of complement: mannose
binding lectin (MBL), ficolins and MBL-associated serine protease-2 (MASP-2), in
144 patients and 98 controls. One hundred and six patients had oligoarticular
disease and 38 had polyarticular disease. In 51 patients (out of 133 tested),
Yersinia-reactive antibodies were found (JIA Ye+ group). MBL deficiency was
significantly more frequent in the JIA Ye+ group than in patients without
Yersinia-reactive antibodies or in controls. Median serum ficolin-2 level was
significantly lower (and proportion of values deemed ficolin-2 insufficient
greater) in JIA patients irrespective of their Yersinia antibody status. The
minority (C) allele at -64 of the FCN2 gene was less frequent among JIA patients
than among control subjects. No differences were found in the frequency of FCN3
gene +1637delC or MASP2 +359 A>G mutations nor for median values of serum ficolin
1, ficolin-3 or MASP-2. However, high levels of serum ficolin-3 were under
represented in patients, in contrast to MBL. MBL, ficolin-1, ficolin-2, ficolin-3
and MASP-2 were also readily detectable in synovial fluid samples but at a
considerably lower level than in serum. Our findings suggest a possible role for
the lectin pathway in the pathogenesis of JIA, perhaps secondary to a role in
host defence, and indicate that investigations on the specificity of lectin
pathway recognition molecules towards specific infectious agents in JIA might be
fruitful.
PMID- 28405018
TI - Observation of the frozen charge of a Kondo resonance.
AB - The ability to control electronic states at the nanoscale has contributed to our
modern understanding of condensed matter. In particular, quantum dot circuits
represent model systems for the study of strong electronic correlations,
epitomized by the Kondo effect. We use circuit quantum electrodynamics
architectures to study the internal degrees of freedom of this many-body
phenomenon. Specifically, we couple a quantum dot to a high-quality-factor
microwave cavity to measure with exceptional sensitivity the dot's electronic
compressibility, that is, its ability to accommodate charges. Because electronic
compressibility corresponds solely to the charge response of the electronic
system, it is not equivalent to the conductance, which generally involves other
degrees of freedom such as spin. Here, by performing dual conductance and
compressibility measurements in the Kondo regime, we uncover directly the charge
dynamics of this peculiar mechanism of electron transfer. The Kondo resonance,
visible in transport measurements, is found to be 'transparent' to microwave
photons trapped in the high-quality cavity, thereby revealing that (in such a
many-body resonance) finite conduction is achieved from a charge frozen by
Coulomb interaction. This freezing of charge dynamics is in contrast to the
physics of a free electron gas. We anticipate that the tools of cavity quantum
electrodynamics could be used in other types of mesoscopic circuits with many
body correlations, providing a model system in which to perform quantum
simulation of fermion-boson problems.
PMID- 28405019
TI - Rad51-mediated double-strand break repair and mismatch correction of divergent
substrates.
AB - The Rad51 (also known as RecA) family of recombinases executes the critical step
in homologous recombination: the search for homologous DNA to serve as a template
during the repair of DNA double-strand breaks (DSBs). Although budding yeast
Rad51 has been extensively characterized in vitro, the stringency of its search
and sensitivity to mismatched sequences in vivo remain poorly defined. Here, in
Saccharomyces cerevisiae, we analysed Rad51-dependent break-induced replication
in which the invading DSB end and its donor template share a 108-base-pair
homology region and the donor carries different densities of single-base-pair
mismatches. With every eighth base pair mismatched, repair was about 14% of that
of completely homologous sequences. With every sixth base pair mismatched, repair
was still more than 5%. Thus, completing break-induced replication in vivo
overcomes the apparent requirement for at least 6-8 consecutive paired bases that
has been inferred from in vitro studies. When recombination occurs without a
protruding nonhomologous 3' tail, the mismatch repair protein Msh2 does not
discourage homeologous recombination. However, when the DSB end contains a 3'
protruding nonhomologous tail, Msh2 promotes the rejection of mismatched
substrates. Mismatch correction of strand invasion heteroduplex DNA is strongly
polar, favouring correction close to the DSB end. Nearly all mismatch correction
depends on the proofreading activity of DNA polymerase-delta, although the repair
proteins Msh2, Mlh1 and Exo1 influence the extent of correction.
PMID- 28405020
TI - Neurodegenerative disease: Two-for-one on potential therapies.
PMID- 28405021
TI - Microbiology: Gut microbes augment neurodegeneration.
PMID- 28405022
TI - Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP
43 mice.
AB - Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative
disease that is characterized by motor neuron loss and that leads to paralysis
and death 2-5 years after disease onset. Nearly all patients with ALS have
aggregates of the RNA-binding protein TDP-43 in their brains and spinal cords,
and rare mutations in the gene encoding TDP-43 can cause ALS. There are no
effective TDP-43-directed therapies for ALS or related TDP-43 proteinopathies,
such as frontotemporal dementia. Antisense oligonucleotides (ASOs) and RNA
interference approaches are emerging as attractive therapeutic strategies in
neurological diseases. Indeed, treatment of a rat model of inherited ALS (caused
by a mutation in Sod1) with ASOs against Sod1 has been shown to substantially
slow disease progression. However, as SOD1 mutations account for only around 2-5%
of ALS cases, additional therapeutic strategies are needed. Silencing TDP-43
itself is probably not appropriate, given its critical cellular functions. Here
we present a promising alternative therapeutic strategy for ALS that involves
targeting ataxin-2. A decrease in ataxin-2 suppresses TDP-43 toxicity in yeast
and flies, and intermediate-length polyglutamine expansions in the ataxin-2 gene
increase risk of ALS. We used two independent approaches to test whether
decreasing ataxin-2 levels could mitigate disease in a mouse model of TDP-43
proteinopathy. First, we crossed ataxin-2 knockout mice with TDP-43 (also known
as TARDBP) transgenic mice. The decrease in ataxin-2 reduced aggregation of TDP
43, markedly increased survival and improved motor function. Second, in a more
therapeutically applicable approach, we administered ASOs targeting ataxin-2 to
the central nervous system of TDP-43 transgenic mice. This single treatment
markedly extended survival. Because TDP-43 aggregation is a component of nearly
all cases of ALS, targeting ataxin-2 could represent a broadly effective
therapeutic strategy.
PMID- 28405023
TI - Particle physics: Strangeness in the proton.
PMID- 28405024
TI - Antisense oligonucleotide therapy for spinocerebellar ataxia type 2.
AB - There are no disease-modifying treatments for adult human neurodegenerative
diseases. Here we test RNA-targeted therapies in two mouse models of
spinocerebellar ataxia type 2 (SCA2), an autosomal dominant polyglutamine
disease. Both models recreate the progressive adult-onset dysfunction and
degeneration of a neuronal network that are seen in patients, including decreased
firing frequency of cerebellar Purkinje cells and a decline in motor function. We
developed a potential therapy directed at the ATXN2 gene by screening 152
antisense oligonucleotides (ASOs). The most promising oligonucleotide, ASO7,
downregulated ATXN2 mRNA and protein, which resulted in delayed onset of the SCA2
phenotype. After delivery by intracerebroventricular injection to ATXN2-Q127
mice, ASO7 localized to Purkinje cells, reduced cerebellar ATXN2 expression below
75% for more than 10 weeks without microglial activation, and reduced the levels
of cerebellar ATXN2. Treatment of symptomatic mice with ASO7 improved motor
function compared to saline-treated mice. ASO7 had a similar effect in the BAC
Q72 SCA2 mouse model, and in both mouse models it normalized protein levels of
several SCA2-related proteins expressed in Purkinje cells, including Rgs8, Pcp2,
Pcp4, Homer3, Cep76 and Fam107b. Notably, the firing frequency of Purkinje cells
returned to normal even when treatment was initiated more than 12 weeks after the
onset of the motor phenotype in BAC-Q72 mice. These findings support ASOs as a
promising approach for treating some human neurodegenerative diseases.
PMID- 28405026
TI - The earliest bird-line archosaurs and the assembly of the dinosaur body plan.
AB - The relationship between dinosaurs and other reptiles is well established, but
the sequence of acquisition of dinosaurian features has been obscured by the
scarcity of fossils with transitional morphologies. The closest extinct relatives
of dinosaurs either have highly derived morphologies or are known from poorly
preserved or incomplete material. Here we describe one of the stratigraphically
lowest and phylogenetically earliest members of the avian stem lineage
(Avemetatarsalia), Teleocrater rhadinus gen. et sp. nov., from the Middle
Triassic epoch. The anatomy of T. rhadinus provides key information that unites
several enigmatic taxa from across Pangaea into a previously unrecognized clade,
Aphanosauria. This clade is the sister taxon of Ornithodira (pterosaurs and
birds) and shortens the ghost lineage inferred at the base of Avemetatarsalia. We
demonstrate that several anatomical features long thought to characterize
Dinosauria and dinosauriforms evolved much earlier, soon after the bird
crocodylian split, and that the earliest avemetatarsalians retained the
crocodylian-like ankle morphology and hindlimb proportions of stem archosaurs and
early pseudosuchians. Early avemetatarsalians were substantially more species
rich, widely geographically distributed and morphologically diverse than
previously recognized. Moreover, several early dinosauromorphs that were
previously used as models to understand dinosaur origins may represent
specialized forms rather than the ancestral avemetatarsalian morphology.
PMID- 28405025
TI - High-avidity IgA protects the intestine by enchaining growing bacteria.
AB - Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by
directly neutralizing virulence factors or by poorly defined mechanisms that
physically impede bacterial interactions with the gut tissues ('immune
exclusion'). IgA-mediated cross-linking clumps bacteria in the gut lumen and is
critical for protection against infection by non-typhoidal Salmonella enterica
subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical
agglutination, which was thought to drive this process, is efficient only at high
pathogen densities (>=108 non-motile bacteria per gram). In typical infections,
much lower densities (100-107 colony-forming units per gram) of rapidly dividing
bacteria are present in the gut lumen. Here we show that a different physical
process drives formation of clumps in vivo: IgA-mediated cross-linking enchains
daughter cells, preventing their separation after division, and clumping is
therefore dependent on growth. Enchained growth is effective at all realistic
pathogen densities, and accelerates pathogen clearance from the gut lumen.
Furthermore, IgA enchains plasmid-donor and -recipient clones into separate
clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is
therefore a mechanism by which IgA can disarm and clear potentially invasive
species from the intestinal lumen without requiring high pathogen densities,
inflammation or bacterial killing. Furthermore, our results reveal an untapped
potential for oral vaccines in combating the spread of antimicrobial resistance.
PMID- 28405028
TI - Women's finger pressure sensitivity at rest and recalled body awareness during
partnered sexual activity.
AB - Greater vibrotactile sensitivity has been related to better erectile function in
men, and vibrotactile and pressure tactile sensitivity have been related to
better sexual function in women. Our previous study found that, for both sexes,
greater recalled body awareness during last sexual relation correlated with
greater recalled desire and arousal. Using the same sample of that study (68
women and 48 men, recruited in the Lisbon area, Portugal), we tested if greater
recalled body awareness during last sexual relation correlates with tactile
pressure sensitivity, as assessed by von Frey microfilaments. In simple and
partial correlations controlling for social desirability and smoking before last
sex, the hypothesis was confirmed for women, but not for men. Greater tactile
sensitivity might enhance sexual arousal through greater awareness of the body
during sex, and/or more frequent and pleasant body sensations during sex might
lead to greater tactile sensitivity in nonsexual situations. Pressure sensitivity
might be more closely linked to sexual arousal in women than in men.
PMID- 28405030
TI - Splitting CO2 with a ceria-based redox cycle in a solar-driven thermogravimetric
analyzer.
AB - Thermochemical splitting of CO2 via a ceria-based redox cycle was performed in a
solar-driven thermogravimetric analyzer. Overall reaction rates, including heat
and mass transport, were determined under concentrated irradiation mimicking
realistic operation of solar reactors. Reticulated porous ceramic (RPC)
structures and fibers made of undoped and Zr4+-doped CeO2, were endothermally
reduced under radiative fluxes of 1280 suns in the temperature range 1200-1950 K
and subsequently re-oxidized with CO2 at 950-1400 K. Rapid and uniform heating
was observed for 8 ppi ceria RPC with mm-sized porosity due to its low optical
thickness and volumetric radiative absorption, while ceria fibers with MUm-sized
porosity performed poorly due to its opacity to incident irradiation. The 10 ppi
RPC exhibited higher fuel yield because of its higher sample density. Zr4+-doped
ceria showed increasing reduction extents with dopant concentration but
decreasing specific CO yield due to unfavorable oxidation thermodynamics and
slower kinetics.
PMID- 28405031
TI - Managing acute post-operative pain: Advances, challenges and constraints.
PMID- 28405029
TI - Protein kinase enzymes in the human vagina-relation to key mediators of the
cyclic AMP and cyclic GMP pathways.
AB - Aside from phosphodiesterase (PDE) isoenzymes, protein kinases (cAK=cyclic AMP
binding protein kinase, cGK=cyclic GMP-binding protein kinase) have also been
identified as important receptors for cyclic nucleotides. A significance of
protein kinases in the control of the function of the male and female
reproductive tract has been suggested; however, up until today, only a few
approaches have addressed these enzymes in female genital tissues. The present
study aimed to investigate by means of biochemical and immunohistochemical
methods the expression of cAK and cGK. The distribution of cAK(I) and cGK(I) in
relation to the vasoactive intestinal polypeptide (VIP), calcitonin gene-related
peptide (CGRP) and PDE type 4 (PDE4) was also evaluated. Cytosolic supernatants
prepared from specimens of vaginal wall smooth muscle or epithelium were
subjected to anion exchange chromatography and the activities of cAK and cGK(I)
measured. To evaluate the distribution of cAK(I) and cGK(I) in relation to VIP,
CGRP and PDE4, immunohistochemistry was conducted in sections of the human
vaginal wall (full-wall specimens). Activities representing cGK(I) and cAK(I)
were resolved from the chromatography column. Staining specific for cAK(Ialpha)
was identified in both vascular and non-vascular vaginal smooth musculature,
immunoreactivity for cGK(Ibeta) was observed in the smooth muscle and endothelium
of small arteries interspersing the sections. cAK(Ialpha)-positive vessels were
found innervated by slender varicose nerve fibers presenting the expression of
VIP and CGRP. These arteries also expressed PDE4. Localization of cAK and cGK in
close relation to key mediators of the cyclic AMP (PDE4, VIP) and cyclic GMP
(CGRP) pathways indicate that both signaling systems may synergistically work
together in human vaginal tissue.
PMID- 28405032
TI - Regulatory requirements for clinical trials in India: What academicians need to
know.
AB - The academician forms the backbone of any medical college, hospital or university
and shoulders the quadruple responsibilities of patient care, teaching,
administration and research. Of these, research, though long and difficult, is
extremely fulfilling. Academicians often carry out research that is based on
observations in practice or in response to their patient's needs. These are
called as "Investigator- initiated studies" and these may not have the funding
support of the pharmaceutical industry. Hence, the investigator must make sure
that he/she complies with the country's regulatory requirements. In the past
decade, several changes have dotted the regulatory landscape in the country and
have changed the way in which academic research is carried out. The present
article outlines regulatory requirements for academic research giving their
historical evolution, the key bodies in India that govern or oversee research,
along with "must know" and "good to know" facets for the conduct of clinical
research in the country.
PMID- 28405027
TI - Virus genomes reveal factors that spread and sustained the Ebola epidemic.
AB - The 2013-2016 West African epidemic caused by the Ebola virus was of
unprecedented magnitude, duration and impact. Here we reconstruct the dispersal,
proliferation and decline of Ebola virus throughout the region by analysing 1,610
Ebola virus genomes, which represent over 5% of the known cases. We test the
association of geography, climate and demography with viral movement among
administrative regions, inferring a classic 'gravity' model, with intense
dispersal between larger and closer populations. Despite attenuation of
international dispersal after border closures, cross-border transmission had
already sown the seeds for an international epidemic, rendering these measures
ineffective at curbing the epidemic. We address why the epidemic did not spread
into neighbouring countries, showing that these countries were susceptible to
substantial outbreaks but at lower risk of introductions. Finally, we reveal that
this large epidemic was a heterogeneous and spatially dissociated collection of
transmission clusters of varying size, duration and connectivity. These insights
will help to inform interventions in future epidemics.
PMID- 28405033
TI - Post-caesarean analgesia: What is new?
AB - Adequate post-operative analgesia after caesarean section (CS) is vital as it
impacts the distinct surgical recovery requirements of the parturient. Although
newer analgesic modalities and drugs for post-caesarean analgesia have been
introduced over the recent years, review of the literature suggests suggests that
we are far from achieving the goals of optimum post-operative analgesia. We
conducted a systematic review of recent advances in modalities for post-caesarean
analgesia. After systematic search and quality assessment of studies, we included
a total of 51 randomised controlled trials that evaluated the role of opioids,
transversus abdominis plane (TAP) block, wound infiltration/infusion, ketamine,
gabapentin and ilioinguinal-iliohypogastric nerve block (II-IH NB) for post
caesarean analgesia. Administration of opioids still remains the gold standard
for post-operative analgesia, but the associated troublesome side effects have
led to the mandatory incorporation of non-opioid analgesics in post-CS analgesia
regime. Among the non-opioid techniques, TAP block is the most investigated
modality of the last decade. The analgesic efficacy of TAP block as a part of
multimodal analgesia is established in post-CS cases where intrathecal morphine
is not employed and in CS under general anaesthesia. Among non-steroidal anti
inflammatory drugs, COX-I inhibitors and intravenous paracetamol are found to be
useful in post-operative analgesic regimen. The perioperative use of ketamine is
found useful only in CS done under spinal anaesthesia; no benefit is seen where
general anaesthesia is employed. Wound infiltration with local anaesthetics,
systemic gabapentin and II-IH NB need further trials to assess their efficacy.
PMID- 28405034
TI - A multicentre survey of the current acute post-operative pain management
practices in tertiary care teaching hospitals in Maharashtra.
AB - BACKGROUND AND AIMS: Undertreated pain can have negative consequences on
patients' health as well as the health-care system. The present study was aimed
at identifying the current trends in post-operative pain management and
availability of acute pain services (APS). In addition, it is also an attempt to
assess the availability of analgesia for non-surgical cases, and the attitudes,
beliefs, and perceptions of clinicians regarding acute pain management in the
tertiary hospitals in the state of Maharashtra (India). METHODS: This was a cross
sectional, multicentre questionnaire survey involving the anaesthesiologists and
surgeons. Percentages, median, interquartile ranges were calculated and compared
by employing a Wilcoxon sign rank test. RESULTS: Data from thirty centres
revealed that the surgeons played a major role in treating pain, while most of
the anaesthesiologists treated pain primarily in the operation theatre and
recovery room. An APS was operational in seven hospitals. The most frequently
employed techniques to achieve analgesia were the administration of non-steroidal
anti-inflammatory drugs, opioids and epidural analgesia. The majority of the
centres had no written protocol and dedicated staff for pain management, pain
assessment was not adequately stressed, and only five out of the thirty centres
included in the study provided ongoing pain education to health professionals
even when the hospitals claimed to provide APS. The major hurdles in providing
optimal analgesia and implementing APS were a lack of pain education, equipment
and administrative problems. CONCLUSION: Thus, the tertiary centres in
Maharashtra fall short of providing optimal acute post-operative pain management.
PMID- 28405035
TI - Safety and efficacy of transdermal buprenorphine versus oral tramadol for the
treatment of post-operative pain following surgery for fracture neck of femur: A
prospective, randomised clinical study.
AB - BACKGROUND: Transdermal buprenorphine, which is used in chronic pain management,
has rarely been studied for use in acute pain management. The aim of this study
was to compare the safety and efficacy of transdermal buprenorphine patch to oral
tramadol for post-operative analgesia, following proximal femur surgeries.
METHODOLOGY: Fifty adult patients undergoing surgery for hip fracture under
spinal anaesthesia were included in this study. One group (Group TDB) received
transdermal buprenorphine 10 mcg/h patch applied a day before the surgery and
other group received oral tramadol 50 mg three times a day for analgesia (Group
OT). They were allowed to take diclofenac and paracetamol tablets for rescue
analgesia. Pain scores at rest, on movement, rescue analgesic requirement and
side effects were compared between the groups over 7 days. Chi-square and
independent sample t-test were used for categorical and continuous variables,
respectively. RESULTS: Resting pain scores and pain on movement were
significantly lower in TDB Group on all 7 days starting from 24 h post
operatively. Rescue analgesic requirement was significantly lower in TDB Group
compared to OT Group. All the patients needed rescue analgesic in OT Group
whereas 68% of the patients needed the same in TDB Group. Incidence of vomiting
was less and satisfaction scores were much higher in TDB Group as compared to OT
Group (79% vs. 66%, P < 0.001). CONCLUSION: Transdermal buprenorphine can be
safely used for post-operative analgesia and is more efficacious in reducing post
operative pain after 24 hours, with fewer side effects when compared to oral
tramadol.
PMID- 28405036
TI - Rapidity and efficacy of ultrasonographic sliding lung sign and auscultation in
confirming endotracheal intubation in overweight and obese patients.
AB - BACKGROUND AND AIMS: Obese individuals are predisposed to difficult airway and
intubation. They usually yield confusing or misleading auscultatory findings. We
aimed to assess the rapidity and efficacy of ultrasonographic (USG) sliding lung
sign for confirming endotracheal intubation in normal as well as overweight and
obese surgical patients. METHODS: This prospective, observational study was
performed in forty surgical patients. Twenty patients with body mass index (BMI)
<25 were recruited to Group A, whereas twenty patients with BMI >=25 constituted
Group B. Following induction and intubation, appearance of end-tidal carbon
dioxide waveform was used to confirm endotracheal intubation. Presence of breath
sounds bilaterally was sought by auscultation, and time taken for auscultatory
confirmation was noted. The USG confirmation of air entry to the lung field as
indicated by lung sliding was sought, and the time taken was noted. Chi-square
test, independent t-test and paired t-test were used as applicable. RESULTS:
Auscultatory confirmation was more rapid in Group A as compared to Group B (9.34
+/- 2.43 s vs. 14.35 +/- 5.53 s, P = 0.001). However, there was no significant
difference in USG confirmation time in both the groups (8.57 +/- 2.05 s vs. 8.61
+/- 1.66 s). Four patients in Group B had doubtful breath sounds against none in
Group A. There was no doubtful lung slide with USG in both groups. One case of
endobronchial intubation in Group B was diagnosed with USG which was doubtful by
auscultation. CONCLUSION: Ultrasound directed confirmation of endotracheal tube
placement in overweight and obese patients is superior in speed and accuracy in
comparison to the standard auscultatory method.
PMID- 28405037
TI - The effect of different dose regimens of tranexamic acid in reducing blood loss
during hip surgery.
AB - BACKGROUND AND AIMS: Antifibrinolytics may help bleeding in orthopaedic
surgeries. The present study was undertaken to compare two dose regimens of
tranexamic acid (TA) on perioperative blood loss in patients undergoing hip
surgeries. METHODS: In a prospective, randomised, controlled study, 59 patients
scheduled for hip surgery were divided into Group C: receiving normal saline (n -
20), Group B: receiving single dose of TA (10 mg/kg) (n - 21), and Group I:
receiving a bolus (10 mg/kg) plus infusion (1 mg/kg/h) of TA up to 4 h
postoperatively (n - 18). Blood loss, haemoglobin and allogeneic blood
transfusions were compared between the groups. For parametric data, P was
calculated by ANOVA. Intergroup comparison was done by post hoc analysis with
Bonferroni test. P < 0.05 was considered significant. RESULTS: The intra
operative blood loss was lower in the patients who received TA (525 +/- 150, 456
+/- 156 and 400 +/- 133 ml in Group C, B and I respectively; P = 0.05). The 6th
hourly drain collection in Group I was lower than Group B and C (41 +/- 18, 46 +/
14 and 31 +/- 14 ml in Group C, B, and I respectively; P = 0.018). The blood
loss at 24 h was less in groups receiving TA (146 +/- 32, 120 +/- 76, 107 +/- 37
ml for Group C, B and I, respectively; P = 0.02). The requirement of blood
transfusions was lower in Group I. CONCLUSIONS: A bolus of tranexamic acid
followed by infusion is more useful than a single dose in decreasing
perioperative blood loss in patients undergoing hip surgeries. It reduces
allogenic blood transfusion without increasing risk of thromboembolic events.
PMID- 28405038
TI - Incidence of posterior wall penetration during internal jugular vein cannulation:
A comparison of two techniques using real-time ultrasound.
AB - BACKGROUND AND AIMS: The true incidence of penetration of the posterior wall
(through-and-through puncture) of the internal jugular vein (IJV) during
cannulation is unknown. This may have implications if there is hematoma
formation, penetration and/or inadvertent cannulation of an underlying carotid
artery. This study compared the incidence of posterior wall puncture during IJV
cannulation using ultrasound guidance versus traditional landmarks-guided
technique. METHODS: One hundred and seventy adult patients admitted to a gastro
liver Intensive Care Unit who required central venous lines were randomly divided
into Group A: IJV cannulation using anatomical landmark-guided technique and
Group B: IJV cannulation using real-time ultrasound guidance. In both groups, a
second investigator followed the needle path using real-time ultrasound. The
incidence of posterior wall puncture, number of attempts for successful
cannulation, incidence of inadvertent arterial punctures and occurrence of
complications such as hematoma formation and pneumothorax were recorded. RESULTS:
Significantly more (37/80, 46%) patients in Group A had posterior wall puncture
compared to 19/90 (21%) in Group B. Incidence of arterial puncture was 8/80 (10%)
in Group A, 5/90 (5.5%) in Group B. The number of attempts for venous cannulation
and hematoma formation was significantly less in Group B. CONCLUSION: Real-time
ultrasound-guided IJV cannulation significantly reduces but does not wholly
eliminate the incidence of posterior venous wall penetrations. It also
significantly reduces the incidence of inadvertent arterial punctures and number
of attempts for successful cannulation.
PMID- 28405039
TI - Disinfection of laryngoscopes: A survey of practice.
AB - BACKGROUND AND AIMS: The laryngoscope is a common piece of equipment used by
anaesthesiologists. It has been identified as a potential source of cross
infection. Although guidelines exist regarding appropriate disinfection
practices, recent reviews suggest ineffectiveness of current methods of
disinfection and poor compliance with the established protocols. We conducted a
questionnaire-based survey to study the current disinfection practices being
followed by a cross section of anaesthesiologists. METHODS: A simple
questionnaire containing 13 questions was distributed amongst anaesthesiologists
in an anaesthesia conference. Data were analysed with percentage analysis.
RESULTS: Out of 250 delegates who attended the conference, 150 submitted the
completed questionnaires. Residents constituted 41% and 46% were consultants.
Eighteen (12%) used only tap water for cleaning and 132 (88%) used a chemical
agent after rinsing with water. Out of 132, 76 (51%) used detergent/soap
solution, 29 (19%) would wash and then soak in disinfectant or germicidal agents
(glutaraldehyde, povidone iodine and chlorhexidine) and 18 (12%) would wipe the
blade with an alcohol swab. With respect to disinfection of laryngoscope handles,
70% respondents said they used an alcohol swab, 18% did not use any method, 9%
were not aware of the method being used, while 3% did not respond. CONCLUSION:
Our results indicate wide variation in methods of decontamination of
laryngoscopes. Awareness regarding laryngoscope as a potential source of
infection was high. We need to standardise and implement guidelines on a national
level and make available resources which will help to improve patient safety.
PMID- 28405040
TI - A dose-finding randomised controlled trial of magnesium sulphate as an adjuvant
in ultrasound-guided supraclavicular brachial plexus block.
AB - BACKGROUND AND AIM: Magnesium sulphate (MgSO4) has been used as an adjuvant in
brachial plexus block with encouraging results; however, there is no consensus
regarding its optimal dose. Thereby, we compared the efficacy of two doses of
MgSO4 as an adjuvant in ultrasound (USG) guided supraclavicular brachial plexus
block. METHODS: Ninety patients, aged 20-60 years, belonging to American Society
of Anesthesiologists physical status 1 or 2, were given USG-guided
supraclavicular block. Group B (n = 30) received 20 ml of 0.5%bupivacaine + 5 ml
normal saline (NS), Group BM0.5(n = 30) received 20 ml of 0.5%bupivacaine + 3.75
ml NS and 125 mg MgSO4 (1.25 ml) and Group BM1(n = 30) received 20 ml of
0.5%bupivacaine + 2.5 ml NS and 250 mg MgSO4 (2.5 ml). The primary outcome of
study was the duration of post-operative analgesia. The normally distributed data
were analysed using analysis of variance and categorical data analysed using Chi
square test. RESULTS: Duration of post-operative analgesia was prolonged in
Groups BM1 and BM0.5 (665.13 +/- 97.874, 475.10 +/- 53.294) min respectively as
compared to Group B (272.03 +/- 40.404 min: P = 0.00). The onset times of sensory
and motor block were shorter in Group BM1 (5.17 +/- 2.2 min) as compared to
Groups BM0.5 and B (8.9 +/- 2.3 and 17.7 +/- 5.1 min: P = 0.00) respectively.
Sensory and motor block durations were prolonged in Group BM1 as compared to
BM0.5 and B (P = 0.00). CONCLUSIONS: MgSO4 as adjuvant in brachial plexus block
increases the duration of post-operative analgesia. MgSO4 in the dose of 250mg
has greater efficacy as compared to 125 mg.
PMID- 28405041
TI - Supraclavicular brachial plexus block: Comparison of varying doses of
dexmedetomidine combined with levobupivacaine: A double-blind randomised trial.
AB - BACKGROUND AND AIMS: The ideal dose of dexmedetomidine for brachial plexus block
is a matter of debate. This study was carried out to evaluate 50 MUg or 100 MUg
of dexmedetomidine added to 0.5% levobupivacaine, with regard to the duration of
analgesia. Our study also sought to assess the onset and duration of sensorimotor
blockade, haemodynamic effects, sedation and adverse effects. METHODS: One
hundred adult patients undergoing upper limb surgeries under supraclavicular
brachial plexus block were randomly allocated into two groups. Group LD50
received 29 ml of 0.5% levobupivacaine plus 50 MUg of dexmedetomidine diluted in
1 ml of normal saline. Group LD100 received 29 ml of 0.5% levobupivacaine plus
100 MUg of dexmedetomidine diluted in 1 ml of normal saline. Duration of
analgesia was the primary outcome. Onset and duration of sensorimotor blockade,
haemodynamic variables, sedation score, and adverse effects were secondary
outcomes. The data were analysed with Students' t-test and Chi-square test.
RESULTS: The onset of sensory block and motor block was 14.82 +/- 3.8 min and
19.75 +/- 6.3 min, respectively, in group LD50, while it was 11.15 +/- 1.7 min
and 14.3 +/- 4.2 min, respectively, in group LD100. The duration of analgesia was
significantly prolonged in group LD100 (1033.6 +/- 141.6 vs. 776.4 +/- 138.6 min;
P = 0.001). The incidence of bradycardia and sedation was observed in
significantly more patients in group LD100. Significantly fewer patients in group
LD100 required rescue analgesia. CONCLUSION: The 100 MUg dose of dexmedetomidine
in brachial plexus block hastens the onset and prolongs the duration of
sensorimotor blockade and analgesia, but with higher incidence of bradycardia and
sedation.
PMID- 28405042
TI - Ultrasonographic measurement of optic nerve sheath diameter: A point of care test
helps in prognostication of Intensive Care Unit patients.
AB - Early identification of elevated intracranial pressure (ICP) is critical to
ensuring timely and appropriate management to improve patient outcome.
Measurement of the optic nerve sheath diameter by ultrasound is a well studied
modality for noninvasive assessment of ICP. Recent studies have shown it to
correlate with invasively measured ICP. We utilized this technique in our ICU and
found it to be of great help in guiding patient management and predicting the
prognosis. A case series of four patients is reported illustrating its utility in
ICU patients.
PMID- 28405043
TI - Anaesthetic management of a child with stone man syndrome: Look before you leap!
AB - Stone Man syndrome or fibrodysplasia ossificans progressiva (FOP) is an extremely
rare (1 in 2 million) genetic disorder characterised by ectopic ossification of
the skeletal and connective tissues leading to progressive fusion of axial and
appendicular skeleton. Surgery and anaesthesia-induced trauma can lead to disease
flare-up if due precautions are not taken and disable the patient further.
However, rarity of the disease may lead to its common misdiagnosis and
anaesthesiologist may be caught unaware. There is relative paucity of literature
regarding anaesthetic management of children with FOP. Videolaryngoscopes (VLs)
provide a non-line-of-sight view and require less anterior force to visualise the
glottis, may provide an alternative to fibreoptic intubation for airway
management in such cases. Use of VL has only been reported once in an adult with
FOP for nasotracheal intubation. We describe the successful anaesthetic
management of an 11-year-old child with FOP and anticipated difficult airway.
PMID- 28405044
TI - Salami publishing and ethical dilemmas facing editors.
PMID- 28405045
TI - Alternative use of the ophthalmic drape for anaesthesia procedures.
PMID- 28405046
TI - Is our suction apparatus rightly calibrated?
PMID- 28405047
TI - A fatal case of pulmonary embolism after lumbar spine surgery.
PMID- 28405048
TI - Congenital factor VII deficiency: Multidisciplinary approach is the key to
successful perioperative outcome.
PMID- 28405049
TI - Use of malfunctioning fibre-optic bronchoscope as a rescue bougie!
PMID- 28405050
TI - Another approach for prone positioning under general anaesthesia.
PMID- 28405051
TI - Nasal septal perforation diagnosed intraoperatively by course of nasotracheal
tube from left nostril to right nostril.
PMID- 28405052
TI - Estimating the Enduring Effects of Fertiliser Subsidies on Commercial Fertiliser
Demand and Maize Production: Panel Data Evidence from Malawi.
AB - Most studies of input subsidy programmes confine their analyses to measuring
programme effects over a one-year period. This article estimates the potential
longer-run or enduring effects of fertiliser subsidy programmes on smallholder
farm households' demand for commercial fertiliser and maize production over time.
We use four waves of panel data on 462 farm households in Malawi for whom
fertiliser use can be tracked for eight consecutive seasons between 2003/2004 and
2010/2011. Panel estimation methods are used to control for potential endogeneity
of subsidised fertiliser acquisition. Results indicate that farmers acquiring
subsidised fertiliser in three consecutive prior years are found to purchase
slightly more commercial fertiliser in the next year. This suggests a small
amount of crowding in of commercial fertiliser from the receipt of subsidised
fertiliser in prior years. In addition, acquiring subsidised fertiliser in a
given year has a modest positive impact on increasing maize output in that same
year. However, acquiring subsidised fertiliser in multiple prior years generates
no statistically significant effect on maize output in the current year. These
findings indicate that potential enduring effects of the Malawi fertiliser
subsidy programme on maize production are limited. Additional interventions that
increase soil fertility can make using inorganic fertiliser more profitable and
sustainable for smallholders in sub-Saharan Africa and thereby increase the cost
effectiveness of input subsidy programmes.
PMID- 28405053
TI - Observed strengthening of interbasin exchange via the Indonesian seas due to
rainfall intensification.
AB - A proxy of the Indonesian Throughflow (ITF) transport, developed using in situ
hydrographic measurements along with assimilations, shows a significant
strengthening trend during the past decade. This trend is due to a freshening and
subsequent increase in the halosteric component of the ITF transport associated
with enhanced rainfall over the Maritime Continent over the same period. The
strengthening of the ITF transport leads to a significant change in heat and
freshwater exchange between the Pacific and Indian Oceans and contributes to the
warming and freshening of the eastern Indian Ocean. The combined effect of the
ITF transport of mass and freshwater along with tropical rainfall plays a very
important role in the climate system.
PMID- 28405054
TI - Enhancing the Capacity of Community Organizations to Evaluate HIV/AIDS
Information Outreach: A Pilot Experiment in Expert Consultation.
AB - The National Library of Medicine's AIDS Community Information Outreach Program
(ACIOP) supports and enables access to health information on the Internet by
community-based organizations. A technical assistance (TA) model was developed to
enhance the capacity of ACIOP awardees to plan, evaluate, and report the results
of their funded projects. This consisted of individual Consultation offered by an
experienced evaluator to advise on the suitability of proposed project plans and
objectives, improve measurement analytics, assist in problem resolution and
outcomes reporting, and identify other improvement possibilities. Group webinars
and a moderated blog for the exchange of project-specific information were also
offered. Structured data collections in the form of reports, online surveys, and
key informant telephone interviews provided qualitative feedback on project
progress, satisfaction with the TA, and the perceived impact of the interventions
on evaluation capacity building. The Model was implemented in the 2013 funding
cycle with seven organizations, and the level of reported satisfaction was
uniformly high. One-on-one TA was requested by four awardee organizations, and
was determined to have made a meaningful difference with three. Participation in
the webinars was mandatory and high overall; and was deemed to be a useful means
for delivering evaluation information. In subsequent funding cycles, submission
of a Logic Model will be required of awardees as a new model intervention in the
expectation that it will produce stronger proposals, and enable the evaluation
consultant to identify earlier intervention opportunities leading to project
improvements and evaluation capacity enhancements.
PMID- 28405055
TI - Stability of a Benzyl Amine Based CO2 Capture Adsorbent in View of Regeneration
Strategies.
AB - In this work, the chemical and thermal stability of a primary amine
functionalized ion-exchange resin (Lewatit VP OC 1065) is studied in view of the
potential options of regenerating this sorbent in a CO2 removal application. The
adsorbent was treated continuously in the presence of air, different O2/CO2/N2
mixtures, concentrated CO2, and steam, and then the remaining CO2 adsorption
capacity was measured. Elemental analysis, BET/BJH analysis, Fourier transform
infrared spectroscopy, and thermogravimetric analysis were applied to
characterize adsorbent properties. This material was found to be thermally and
hydrothermally stable at high temperatures. However, significant oxidative
degradation occurred already at moderate temperatures (above 70 degrees C).
Temperatures above 120 degrees C lead to degradation in concentrated dry CO2.
Adding moisture to the concentrated CO2 stream improves the CO2-induced
stability. Adsorbent regeneration with nitrogen stripping is studied with various
parameters, focusing on minimizing the moles of purge gas required per mole of
CO2 desorbed.
PMID- 28405056
TI - Energy-Efficient Routes for the Production of Gasoline from Biogas and Pyrolysis
Oil-Process Design and Life-Cycle Assessment.
AB - Two novel routes for the production of gasoline from pyrolysis oil (from timber
pine) and biogas (from ley grass) are simulated, followed by a cradle-to-gate
life-cycle assessment of the two production routes. The main aim of this work is
to conduct a holistic evaluation of the proposed routes and benchmark them
against the conventional route of producing gasoline from natural gas. A
previously commercialized method of synthesizing gasoline involves conversion of
natural gas to syngas, which is further converted to methanol, and then as a last
step, the methanol is converted to gasoline. In the new proposed routes, the
syngas production step is different; syngas is produced from a mixture of
pyrolysis oil and biogas in the following two ways: (i) autothermal reforming of
pyrolysis oil and biogas, in which there are two reactions in one reactor (ATR)
and (ii) steam reforming of pyrolysis oil and catalytic partial oxidation of
biogas, in which there are separated but thermally coupled reactions and reactors
(CR). The other two steps to produce methanol from syngas, and gasoline from
methanol, remain the same. The purpose of this simulation is to have an ex-ante
comparison of the performance of the new routes against a reference, in terms of
energy and sustainability. Thus, at this stage of simulations, nonrigorous,
equilibrium-based models have been used for reactors, which will give the best
case conversions for each step. For the conventional production route, conversion
and yield data available in the literature have been used, wherever available.The
results of the process design showed that the second method (separate, but
thermally coupled reforming) has a carbon efficiency of 0.53, compared to the
conventional route (0.48), as well as the first route (0.40). The life-cycle
assessment results revealed that the newly proposed processes have a clear
advantage over the conventional process in some categories, particularly the
global warming potential and primary energy demand; but there are also some in
which the conventional route fares better, such as the human toxicity potential
and the categories related to land-use change such as biotic production potential
and the groundwater resistance indicator. The results confirmed that even though
using biomass such as timber pine as raw material does result in reduced
greenhouse gas emissions, the activities associated with biomass, such as
cultivation and harvesting, contribute to the environmental footprint,
particularly the land use change categories. This gives an impetus to investigate
the potential of agricultural, forest, or even food waste, which would be likely
to have a substantially lower impact on the environment. Moreover, it could be
seen that the source of electricity used in the process has a major impact on the
environmental performance.
PMID- 28405057
TI - How to reveal people's preferences: Comparing time consistency and predictive
power of multiple price list risk elicitation methods.
AB - The question of how to measure and classify people's risk preferences is of
substantial importance in the field of economics. Inspired by the multitude of
ways used to elicit risk preferences, we conduct a holistic investigation of the
most prevalent method, the multiple price list (MPL) and its derivations. In our
experiment, we find that revealed preferences differ under various versions of
MPLs as well as yield unstable results within a 30-minute time frame. We
determine the most stable elicitation method with the highest forecast accuracy
by using multiple measures of within-method consistency and by using behavior in
two economically relevant games as benchmarks. A derivation of the well-known
method by Holt and Laury (American Economic Review 92(5):1644-1655, 2002), where
the highest payoff is varied instead of probabilities, emerges as the best MPL
method in both dimensions. As we pinpoint each MPL characteristic's effect on the
revealed preference and its consistency, our results have implications for
preference elicitation procedures in general.
PMID- 28405058
TI - Area-Selective Atomic Layer Deposition of In2O3:H Using a MU-Plasma Printer for
Local Area Activation.
PMID- 28405059
TI - Uniform Atomic Layer Deposition of Al2O3 on Graphene by Reversible Hydrogen
Plasma Functionalization.
AB - A novel method to form ultrathin, uniform Al2O3 layers on graphene using
reversible hydrogen plasma functionalization followed by atomic layer deposition
(ALD) is presented. ALD on pristine graphene is known to be a challenge due to
the absence of dangling bonds, leading to nonuniform film coverage. We show that
hydrogen plasma functionalization of graphene leads to uniform ALD of closed
Al2O3 films down to 8 nm in thickness. Hall measurements and Raman spectroscopy
reveal that the hydrogen plasma functionalization is reversible upon Al2O3 ALD
and subsequent annealing at 400 degrees C and in this way does not deteriorate
the graphene's charge carrier mobility. This is in contrast with oxygen plasma
functionalization, which can lead to a uniform 5 nm thick closed film, but which
is not reversible and leads to a reduction of the charge carrier mobility.
Density functional theory (DFT) calculations attribute the uniform growth on both
H2 and O2 plasma functionalized graphene to the enhanced adsorption of
trimethylaluminum (TMA) on these surfaces. A DFT analysis of the possible
reaction pathways for TMA precursor adsorption on hydrogenated graphene predicts
a binding mechanism that cleans off the hydrogen functionalities from the
surface, which explains the observed reversibility of the hydrogen plasma
functionalization upon Al2O3 ALD.
PMID- 28405060
TI - Personalized treatment of heart failure with biomarker guidance using a novel
disease severity score.
AB - We propose a novel Myocardial Injury Summary Score (MISS) integrating the 4
biomarkers suggested by the 2013 American College of Cardiology/American Heart
Association guidelines for management of heart failure. In this case series, we
examined 4 heart failure patients who received treatment guided by the biomarker
results and 4 patients who received routine clinical management with no
information about the biomarkers. Most of the patients receiving biomarker-guided
management had medications adjusted based on the biomarker values, while no
changes were recommended for patients in the biomarker-blinded category. This
case series suggests that biomarker-guided therapy with serial biomarker values
leads to timely therapeutic adjustment and that biomarker values as a composite
score can be used effectively to measure the severity of heart failure.
PMID- 28405061
TI - Emergency department discharge prescription errors in an academic medical center.
AB - This study described discharge prescription medication errors written for
emergency department patients. This study used content analysis in a cross
sectional design to systematically categorize prescription errors found in a
report of 1000 discharge prescriptions submitted in the electronic medical record
in February 2015. Two pharmacy team members reviewed the discharge prescription
list for errors. Open-ended data were coded by an additional rater for agreement
on coding categories. Coding was based upon majority rule. Descriptive statistics
were used to address the study objective. Categories evaluated were patient age,
provider type, drug class, and type and time of error. The discharge prescription
error rate out of 1000 prescriptions was 13.4%, with "incomplete or inadequate
prescription" being the most commonly detected error (58.2%). The adult and
pediatric error rates were 11.7% and 22.7%, respectively. The antibiotics
reviewed had the highest number of errors. The highest within-class error rates
were with antianginal medications, antiparasitic medications, antacids, appetite
stimulants, and probiotics. Emergency medicine residents wrote the highest
percentage of prescriptions (46.7%) and had an error rate of 9.2%. Residents of
other specialties wrote 340 prescriptions and had an error rate of 20.9%. Errors
occurred most often between 10:00 am and 6:00 pm.
PMID- 28405062
TI - Pre and post hoc analysis of electronic health record implementation on emergency
department metrics.
AB - Longitudinal time-based emergency department (ED) performance measures were
quantified 12 months before and 12 months after (March 2012-February 2014)
implementation of a Meditech 6.0(r) electronic health record (EHR) at a single
urban academic ED. Data assessed were length of stay from door to door, door to
admission, door to bed, bed to provider, provider to disposition, and disposition
to admission, as well as number of patients leaving against medical advice and
number of patients leaving without being seen. Analysis of variance was used to
compare levels before and after EHR implementation for each variable, with
adjustments made for the number of admissions, transfers, and month. No
difference was seen in monthly volume, admissions, or transfers. Implementation
of an EHR resulted in a sustained increase in ED time metrics for mean length of
stay and times from door to door, door to admission, door to bed, and provider to
disposition. Decreased ED time metrics were seen in bed-to-provider and
disposition-to-admit times. The number of patients who left against medical
advice increased after implementation, but the number of patients who left
without being seen was not significantly different. Thus, EHR implementation was
associated with an increase in time with most performance metrics. Although
general times trended back to near preimplementation baselines, most ED time
metrics remained elevated beyond the study length of 12 months. Understanding the
impact of EHR system implementation on the overall performance of an ED can help
departments prepare for potential adverse effects of such systems on overall
efficiency.
PMID- 28405063
TI - Perineal body length and perineal lacerations during delivery in primigravid
patients.
AB - This study assessed the relation between perineal body length and the risk of
perineal laceration extending into the anal sphincter during vaginal delivery in
primigravid patients at an institution with a low utilization of episiotomy. This
was a prospective study of primigravid patients in active labor. Primigravid
women with singleton pregnancies who were in the first stage of labor at 37 weeks
gestation or greater were recruited, and the admitting physician measured the
length of the perineal body. The degree of perineal laceration and other delivery
characteristics were recorded. Data were analyzed using univariate analyses,
receiver-operator curve analyses, and multiple logistic regression for factors
associated with increased severity of vaginal lacerations. The perineal body
length, duration of second stage of labor, type of delivery, and patient age were
associated (P < 0.1) with third- and fourth-degree (severe) perineal lacerations
in primigravid women using receiver-operator curve analysis. Using logistic
regression, only the duration of second stage of labor and length of the perineal
body were significant (P < 0.04) predictors of third- and fourth-degree
lacerations, with odds ratios of 32 (1.3 to 807 as 95% CI) and 24 (1.3 to 456),
respectively. Both a perineal body length of <=3.5 cm and a duration of second
stage of labor >99 minutes were associated with an increased risk of third- and
fourth-degree lacerations in primigravid patients.
PMID- 28405064
TI - Anatomic relation between single-incision slings and the obturator vessels.
AB - The risk of arterial vascular injury within the retropubic space is a potentially
life-threatening complication associated with mid-urethral sling placement for
the treatment of female stress urinary incontinence. To determine the
relationship between the major blood vessels and a single incision sling, these
slings were placed in 12 fresh female cadavers. Following the insertion of each
sling, the retropubic space was dissected and sling placement was observed
relative to the obturator neurovascular bundle bilaterally. The distance between
the most distal aspect of each sling arm, or the point of anchoring, was measured
from the most medial aspect of the obturator vessels bilaterally. The mean
distance between each sling arm and the medial portion of the obturator vessels
was an average of 3.4 cm (range 2.0-6.0 cm) in 24 observations. Placement of the
single incision sling may have a lower risk of injuring major vessels within the
retropubic space compared to full-length mid-urethral slings.
PMID- 28405065
TI - Practical and ethical considerations in the management of pacemaker and
implantable cardiac defibrillator devices in terminally ill patients.
AB - More than 4.5 million people worldwide live with an implanted pacemaker,
including >3 million in the USA alone. Also, >0.8 million people in the USA have
an implantable cardioverter defibrillator (ICD). Knowing the principles of
managing these devices towards the end of life is important, as the interruption
of their function may have serious consequences. This article provides health
care providers who are not specialized in cardiac electrophysiology with an
introduction to the general principles of management of pacemakers or ICD devices
towards the end of life, with a suggested algorithm for approaching this process.
Also discussed are pertinent ethical and practical considerations in deciding on
and implementing a management strategy for these devices during terminal
illnesses.
PMID- 28405066
TI - Relation of left ventricular free wall rupture and/or aneurysm with acute
myocardial infarction in patients with aortic stenosis.
AB - This minireview describes 6 previously reported patients with left ventricular
free wall rupture and/or aneurysm complicating acute myocardial infarction (AMI)
in patients with aortic stenosis. The findings suggest that left ventricular
rupture and/or aneurysm is more frequent in patients with AMI associated with
aortic stenosis than in patients with AMI unassociated with aortic stenosis,
presumably because of retained elevation of the left ventricular peak systolic
pressure after the appearance of the AMI.
PMID- 28405067
TI - Heterogeneity of systematic reviews in oncology.
AB - Systematic reviews synthesize data across multiple studies to answer a research
question, and an important component of the review process is to evaluate the
heterogeneity of primary studies considered for inclusion. Little is known,
however, about the ways that systematic reviewers evaluate heterogeneity,
especially in clinical specialties like oncology. We examined a sample of
systematic reviews from this body of literature to determine how meta-analysts
assessed and reported heterogeneity. A PubMed search of 6 oncology journals was
conducted to locate systematic reviews and meta-analyses. Two coders then
independently evaluated the manuscripts for 10 different elements based on an
abstraction manual. The initial PubMed search yielded 337 systematic reviews from
6 journals. Screening for exclusion criteria (nonsystematic reviews, genetic
studies, individual patient data, etc.) found 155 articles that did not meet the
definition of a systematic review. This left a final sample of 182 systematic
reviews across 4 journals. Of these reviews, 50% (91/182) used varying
combinations of heterogeneity tests, and of those, 16% (15/91) of review authors
noted excessive heterogeneity and opted to not perform a meta-analysis. Of the
studies that measured heterogeneity, 51% (46/91) used a random-effects model, 7%
(8/91) used a fixed-effects model, and 43% (39/91) used both. We conclude that
use of quantitative and qualitative heterogeneity measurement tools are underused
in the 4 oncology journals evaluated. Such assessments should be routinely
applied in meta-analyses.
PMID- 28405068
TI - Hemodialysis failure secondary to hydroxocobalamin exposure.
AB - Hydroxocobalamin is a recently approved antidote for the treatment of cyanide
poisoning. The case presented involves a young patient administered empiric
hydroxocobalamin due to suspected cyanide overdose. Due to the development of
acute kidney injury and severe metabolic derangement, emergent hemodialysis was
initiated. Unfortunately, hemodialysis was confounded by a recurrent "blood leak"
alarm. This unforeseen effect was secondary to interference from
hydroxocobalamin. Hydroxocobalamin causes orange/red discoloration of bodily
fluids and permeates the dialysate. This leads to defraction of light in the
effluent path of the blood leak detector from discolored dialysate, which can
result in activation of the blood leak alarm and an inability to continue
hemodialysis treatment. This case highlights several new and emerging critical
concerns with this medication, including the potential consequence of delayed
initiation of emergent renal replacement therapy with empiric administration, the
need for increased awareness among clinicians of various disciplines, and the
need for multidisciplinary communication.
PMID- 28405069
TI - Acquired 5-oxoproline acidemia successfully treated with N-acetylcysteine.
AB - Acquired 5-oxoprolinemia is increasingly recognized as a cause of anion gap
metabolic acidosis. It predominantly occurs in chronically ill, malnourished
women with impaired renal function and chronic acetaminophen ingestion. Depletion
of glutathione and cysteine stores leads to elevated 5-oxoproline levels. N
acetylcysteine, given its effect in repleting glutathione and cysteine stores,
has been proposed as a potential treatment for 5-oxoprolinemia, though reports of
its successful use are lacking. We present a case of 5-oxoproline metabolic
acidosis that persisted despite discontinuation of acetaminophen. However, the
acidosis rapidly resolved with N-acetylcysteine administration.
PMID- 28405070
TI - Nitrous oxide-induced vitamin B12 deficiency.
AB - Nitrous oxide is a gas that is odorless, colorless, and has a sweet taste at room
temperature. Nitrous oxide has several uses, including in surgery and dentistry
(referred to as "laughing gas"), in automotive racing, and in aerosol spray
propellants. The aerosol spray propellants that typically use nitrous oxide are
whipped cream canisters and cooking sprays. Unfortunately, these over-the-counter
household items are a source of nitrous oxide that can be used for recreational
use. The most popular is the use of industrial-grade canisters having the slang
term "whippets." The nitrous oxide can be extracted by pushing the nozzle down
slightly to the side and catching the released gas with a balloon. The contents
of the balloon can then be directly inhaled, giving an instant feeling of
euphoria. This is not a benign means to achieve a euphoric state but can cause
severe nitrous oxide-induced B12 deficiency, which is presented in this case
report.
PMID- 28405071
TI - Systemic infection and splenic abscess.
AB - Splenic abscess is a rare complication of systemic infection, sometimes
associated with infective endocarditis. Due to its rarity and nonspecific
symptoms, diagnosis is difficult. Antibiotic therapy alone is usually
unsuccessful, and definitive treatment requires splenectomy, although
percutaneous ultrasound-guided drainage has been successful in some patients.
Abdominal computed tomography scans and ultrasound evaluation are usually
diagnostic. We present two patients with treatment-resistant sepsis who were
found at autopsy to have splenic abscess.
PMID- 28405072
TI - Tularemia presenting as pulmonary nodules in an immunocompromised patient.
AB - Tularemia is a zoonotic disease caused by Francisella tularensis that can be
transmitted to humans when they handle rabbits, receive tick bites, consume
contaminated water, or inhale aerosolized particles. We present the case of a 51
year-old white man with rheumatoid arthritis who was taking immunosuppressive
medications and presented with tularemia. Our patient acquired the typhoidal form
of tularemia, which is a severe systemic illness that manifests with fevers,
headaches, myalgias, vomiting, diarrhea, and neurological symptoms, due to his
immunocompromised state. The diagnosis was made through biopsy of a pulmonary
nodule found incidentally on computed tomography scan.
PMID- 28405073
TI - Benign pancreatic hyperenzymemia (Gullo syndrome), histamine intolerance, and
carbohydrate malabsorption.
AB - Benign pancreatic hyperenzymemia (Gullo syndrome) is characterized by a more than
threefold increase of the pancreatic enzymes lipase and amylase in the absence of
a pancreatic disease over a period of more than 1 year, with elevations and
significant undulations of pancreatic enzyme serum concentrations occurring on a
day-to-day basis for 5 consecutive days. Nonspecific abdominal complaints may be
caused by carbohydrate and/or protein malabsorption. We report a patient with
benign pancreatic hyperenzymemia with lactose and histamine malabsorption; the
symptoms of gastrointestinal malabsorption were treated successfully with an
individually tailored lactose- and histamine-free diet.
PMID- 28405074
TI - Pott puffy tumor.
AB - Pott puffy tumor is osteomyelitis of the frontal bone with associated
subperiosteal abscess causing swelling and edema over the forehead and scalp. It
is a complication of frontal sinusitis or trauma. We present the case of an 8
year-old girl with frontal swelling. Imaging evaluation showed frontal
osteomyelitis as a complication of frontal sinusitis with associated epidural and
subperiosteal abscess. The patient was treated surgically and recovered well.
This case highlights the need for high clinical suspicion and early diagnosis and
management to prevent life-threatening complications. Unfortunately, in our case
the patient had to undergo surgery for this complication, which could have been
prevented by earlier diagnosis.
PMID- 28405075
TI - Acquired thrombotic thrombocytopenic purpura and atypical hemolytic uremic
syndrome successfully treated with eculizumab.
AB - Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening
disease with a mortality of up to 90%, if not promptly recognized and treated. We
report a 64-year-old woman with this condition who presented with left-sided
weakness and seizure-like activity preceded by headache and easy bruising. She
did not achieve optimal response to plasma exchange, corticosteroids, rituximab,
and vincristine. We initiated treatment with eculizumab, following which she had
durable remission that continued for 30 months after discontinuation of the drug.
We later found that our patient has homozygous deletion in two closely related
genes, complement factor H-related 1 and complement factor H-related 3.
PMID- 28405076
TI - A rare hemoglobin variant, Hb Belliard.
AB - There are many documented variants of hemoglobin; however, other than a limited
number (such as sickle cell disease), very few are known to have any clinical
significance. As advances in detection and identification continue through gel
electrophoresis, capillary electrophoresis, and DNA sequencing, more rare
variants are identified. Without case reporting, the significance of these
variants will remain unknown or continue to be thought of as insignificant. Here
we report a rare hemoglobin variant, Hb Belliard, which was detected in a 68-year
old Indian immigrant to the United States. He presented with elevated hemoglobin
and was found to have a unique peak on capillary electrophoresis. The specimen
was sent for sequencing and was subsequently found to have Hb Belliard.
Currently, Hb Belliard is thought to be insignificant.
PMID- 28405077
TI - Asian-variant intravascular large B-cell lymphoma.
AB - Intravascular large B-cell lymphoma (IVLBCL) is a rare and deadly malignancy
involving the growth of lymphoma cells within vessel lumina of all organ types.
IVLBCL is further divided into the hemophagocytic Asian variant and a classical
Western variant. Both variants are difficult to diagnose by imaging, and although
diagnostic criteria have been developed to guide workup, histopathological
examination remains imperative. Treatment of IVLBCL remains difficult given the
high mortality of the disease, but rituximab has emerged as a promising
therapeutic option when combined with various cytotoxic regimens. The two main
variants of IVLBCL generally manifest in their respective Asian or Western
populations, and crossover between ethnicities is rare. We present the second
described case of Asian-variant IVLBCL in an African American individual.
PMID- 28405078
TI - Bile duct lymphoma disguised as cholangiocarcinoma.
AB - We present a case of intrabiliary primary B-cell lymphoma masked as a
cholangiocarcinoma in an HIV-positive patient. The two entities have similar
symptoms, laboratory findings, and imaging findings but require very different
treatments. The case highlights the need to confirm the diagnosis by biopsy.
PMID- 28405079
TI - Plasma cell myeloma with lymphoplasmacytic morphology and cyclin D1 expression,
an uncommon variant.
AB - The genetic complexity of multiple myeloma is due in part to the accumulation of
mutations, with primary and secondary events. One such secondary event is the
development of a gene mutation that may result in overexpression of cyclin D1.
The pathway involving cyclin D1 is intricately involved in cell cycle regulation
from the G1 to S phase, and alterations may contribute to tumorigenesis. We
present a case of cyclin D1-positive multiple myeloma with lymphoplasmacytic
morphology and discuss potential diagnostic pitfalls and effects on prognosis.
PMID- 28405080
TI - Myeloid sarcoma causing airway obstruction.
AB - Myeloid sarcoma is an extramedullary collection of blasts of the myeloid series
that partially or totally effaces the architecture of the tissue in which it is
found. These tumors have been described in many sites of the body, but the skin,
lymph nodes, gastrointestinal tract, bone, soft tissue, and testes are most
common. They can arise in a patient following the diagnosis of acute myeloid
leukemia, but they may also be precursors of leukemia and should be considered
diagnostic for acute myeloid leukemia. The differential diagnosis of this
neoplasm includes malignant lymphoma, with which it is often mistaken, leading to
diagnostic and therapeutic delays. We present the case of an 84-year-old African
American man with a history of renal disease secondary to hypertension and
coronary artery disease without any prior history of malignancies who presented
with airway obstruction. He was diagnosed with a myeloid sarcoma of the
mediastinum compressing his trachea.
PMID- 28405081
TI - Diagnosis of sarcoidosis from a biopsy of a dilated mammary duct.
AB - Sarcoidosis is an immunologic disease of unknown etiology that manifests most
frequently within the lungs or associated lymph nodes. Sarcoidosis involving the
breast is seen in <1% of cases and usually is diagnosed in patients with
multisystem disease. The clinical and imaging presentations of sarcoidosis of the
breast can be variable. Though uncommon, sarcoidosis should be considered in the
differential diagnosis of a breast lesion, and given that imaging characteristics
cannot distinguish between sarcoidosis and malignancy, all breast lesions in
patients with sarcoidosis should be biopsied. Our case study demonstrates a
diagnosis of sarcoidosis in an asymptomatic patient presenting with a single
dilated duct and associated filling defect within the right breast.
PMID- 28405082
TI - Primary small-cell carcinoma of the breast.
AB - Early diagnosis of rare breast cancers is expected to occur more frequently as
screening compliance improves and diagnostic modalities become more sensitive.
Well-defined treatment algorithms exist for the management of ductal and lobular
carcinomas; however, less information is available to guide the treatment of
atypical breast cancers. This case report describes a 38-year-old African
American woman with primary small cell carcinoma of the breast and her treatment.
PMID- 28405083
TI - Plasmablastic plasmacytoma of the breast.
AB - Breast plasmacytomas are extremely rare entities that can be seen as primary
malignant neoplasms in the absence of bone involvement or as secondary neoplasms
from disseminated multiple myeloma. Clinicians should be aware of this entity, as
it may mimic benign and malignant lesions in the breast. Microscopically,
immature plasmacytomas may mimic other neoplasms, so caution should be made on
histological examination to ensure the correct diagnosis and corresponding
therapy. Here we present a case of a plasmablastic plasmacytoma of the breast in
a 55-year-old woman that was originally thought to be an angiosarcoma.
PMID- 28405084
TI - Primitive neuroectodermal tumors of the kidney.
AB - Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) rarely occurs as a
primary renal tumor. The disease affects young adults and children and has an
aggressive course. The clinical presentation and imaging of these tumors are
nonspecific, and they often present at an advanced stage. We present the clinical
features, imaging, diagnosis, and treatment of 7 cases of renal PNET (4 men, 3
women; median age, 32 years). Common presenting symptoms were flank or abdominal
pain and a mass in the abdomen. On imaging, a large heterogenous infiltrating
renal mass with areas of calcification, hemorrhage, and necrosis and tumor
thrombus can give a clue to the diagnosis of renal PNET. Immunohistochemistry and
molecular studies are essential to confirm the diagnosis. The prognosis of renal
ES/PNET is generally poor. Radical nephrectomy combined with chemotherapy and
radiotherapy is the standard treatment for renal PNET. An early and accurate
diagnosis is crucial for the proper management of these aggressive tumors.
PMID- 28405085
TI - Giant cystic umbilical cord associated with patent urachus and intrauterine fetal
demise.
AB - True cystic structures within the umbilical cord are rare, and when they persist
into the second and third trimester, they are often associated with an abnormal
karyotype or other developmental abnormalities. Clinically significant
pseudocysts resulting from massive edema of the umbilical cord have been
associated with a congenitally patent urachus. We present a case of intrauterine
fetal demise at 28 weeks' gestation in which cystic dilatation of the umbilical
cord was diagnosed prenatally by ultrasound imaging. At autopsy, a congenitally
patent urachus was contiguous with the massively edematous umbilical cord.
PMID- 28405086
TI - Evaluation and management of an unusual congenital nevus.
AB - Abnormal findings on routine skin exams are common and can be a source of
unnecessary medical workup if a clinician is unfamiliar with the finding.
Sebaceous nevi are rare skin lesions that are most often benign but may be
associated with a multiorgan syndrome or local skin cancer. Dermatologists and
primary care physicians may encounter these on routine exams and thus must be
comfortable with diagnosis and management. We present the clinical
characteristics of a benign sebaceous nevus to help aid in diagnosis of these
lesions and outline suggestions for appropriate management options.
PMID- 28405087
TI - Leukocytoclastic vasculitis drug reaction to certolizumab pegol.
AB - Tumor necrosis factor (TNF)-alpha antagonists are a common treatment modality for
autoimmune disorders, but their use can be associated with many side effects,
including various dermatologic conditions. Certolizumab pegol, a newer TNF
antagonist that lacks the Fc portion of the IgG antibody, has recently been
approved to treat psoriatic arthritis, rheumatoid arthritis, and Crohn's disease.
Though other TNF antagonists have been associated with leukocytoclastic
vasculitis, this finding has not yet been reported with certolizumab pegol. We
present a case report of leukocytoclastic vasculitis caused by certolizumab
pegol.
PMID- 28405088
TI - Dural arteriovenous fistula as a treatable dementia.
AB - Dementia is a chronic loss of neurocognitive function that is progressive and
irreversible. Although rare, dural arteriovenous fistulas (DAVFs) could present
with a rapid decline in neurocognitive function with or without Parkinson-like
symptoms. DAVFs represent a potentially treatable and reversible cause of
dementia. Here, we report the case of an elderly woman diagnosed with a DAVF
after presenting with new-onset seizures, deteriorating neurocognitive function,
and Parkinson-like symptoms.
PMID- 28405089
TI - Right hemispheric reversible cerebral vasoconstriction syndrome in a patient with
left hemispheric partial seizures.
AB - We report a right-handed 19-year-old girl who developed reversible cerebral
vasoconstriction syndrome (RCVS) lateralized to the right hemisphere with
simultaneous new-onset left hemispheric seizures. RCVS, typically more diffuse,
was lateralized to one of the cerebral hemispheres.
PMID- 28405090
TI - Bilateral respiratory epithelial adenomatoid hamartomas originating from the
anterior olfactory clefts.
AB - A respiratory epithelial adenomatoid hamartoma (REAH) is an uncommon benign
lesion often found in the sinonasal tract. We present a case of bilateral REAH
originating from the anterior olfactory cleft treated with endoscopic surgical
resection without recurrence. We highlight the characteristics of REAH and
necessary steps to ensure proper diagnosis and treatment.
PMID- 28405091
TI - Ambulatory extracorporeal membrane oxygenation with subclavian venoarterial
cannulation to increase mobility and recovery in a patient awaiting cardiac
transplantation.
AB - Venoarterial extracorporeal membrane oxygenation (ECMO) can provide temporary
cardiopulmonary support for patients in hemodynamic extremis or refractory heart
failure until more durable therapies-such as cardiac transplantation or a left
ventricular assist device-can be safely implemented. Conventional ECMO
cannulation strategies commonly employ the femoral artery and vein, constraining
the patients to the supine position for the duration of ECMO support. We have
recently adopted a modified cannulation approach to promote patient mobility,
rehabilitation, and faster recovery and to mitigate complications associated with
femoral arterial cannulation, such as limb ischemia and compartment syndrome.
This technique involves cannulation of the subclavian artery and vein. The
current case report details our recent experience with this approach in a
critically ill patient awaiting cardiac transplantation.
PMID- 28405092
TI - Use of a MitraClip for severe mitral regurgitation in a cardiac transplant
patient.
AB - Severe mitral regurgitation (MR) in patients after cardiac transplant has not
been well studied. Traditionally, patients have undergone corrective surgery. We
report a 64-year-old man who presented with new heart failure symptoms 6 months
after cardiac transplantation. He was found to have severe MR and underwent
successful implantation of a MitraClip(r) with reduction of his MR to mild as
well as improvement in his symptoms. Six months later he was still doing well,
and a repeat echocardiogram showed good results. We found two previously reported
cases using the MitraClip to treat severe MR in adult cardiac transplant
patients. The MitraClip is a viable treatment option for MR in cardiac transplant
patients despite their distorted anatomy.
PMID- 28405093
TI - Two causes in one patient for extremely low voltage on the electrocardiogram.
AB - An 80-year-old woman is described with two different causes (pericardial effusion
and cardiac amyloidosis) for low QRS voltage on the electrocardiogram. Total 12
lead QRS voltage (from the peak of the R wave to the nadir of either the Q or the
S wave, whichever is deeper) was only 34 mm (10 mm standard in all leads), the
lowest we have encountered among 331 previously reported patients with 10
different cardiac conditions.
PMID- 28405094
TI - Successful treatment of a cardiac resynchronization therapy nonresponder by
identifying lead malpositioning.
AB - This case describes some of the commonly overlooked device-related issues in
patients who have reportedly failed to respond to cardiac resynchronization
therapy (CRT). The case demonstrates voltage-dependent right ventricular capture
instead of right atrial capture by a subtly malpositioned right atrial lead. CRT
therapy failed to improve symptoms of heart failure and the diagnosis of "CRT
nonresponder" was made. With a detailed fact-finding approach, the mechanism
behind this nonresponse was identified, and the outcome of CRT was significantly
improved with rectification of the problems.
PMID- 28405095
TI - Atrial fibrillation 50 years after acute rheumatic fever as the first
manifestation of rheumatic mitral stenosis.
PMID- 28405096
TI - Cardiac rehabilitation for a skydiver after aortic valve replacement for pure
aortic regurgitation and resection of the ascending aorta complicated by active
infective endocarditis and heart block requiring a pacemaker.
AB - A professional skydiver underwent aortic valve and ascending aorta replacement
complicated by infective endocarditis with root abscess and pacemaker
implantation. He then enrolled in the Baylor Heart and Vascular Hospital cardiac
rehabilitation (CR) program as part of its specificity of testing and exercise
training facility. He performed specific skydiving cardiovascular and muscular
strength tests at the beginning and the end of the CR program. His pacemaker was
interrogated to ascertain any arrhythmias or lead displacement over the course of
the CR program. Daily exercise training was customized to match the physical
demands of skydiving, including two sessions at iFLY Dallas. Upon completion of
the daily exercise sessions, the patient performed a simulated free-fall drop
test. He then performed a true jump at Dallas Skydive Center and subsequently
traveled to Arizona for a skydiving competition, where he performed 35 true jumps
with no adverse events or symptoms. This case illustrates how CR, tailored to a
patient's specific needs, can aid in the return to rigorous activity.
PMID- 28405097
TI - Tribute to Dr. John Hyland.
PMID- 28405099
TI - TBA for OT HHC vs OPC f/u.
PMID- 28405098
TI - From my little black notebook: lessons for young physicians and medical students.
PMID- 28405100
TI - Facts and ideas from anywhere.
PMID- 28405101
TI - The Feasibility Study of a Hybrid Coplanar Arc Technique Versus Hybrid Intensity
modulated Radiotherapy in Treatment of Early-stage Left-sided Breast Cancer with
Simultaneous-integrated Boost.
AB - This study demonstrated the feasibility and advantages of a hybrid, volumetric
arc therapy technique that used two 90 degrees coplanar arcs and two three
dimensional conformal tangential beams in the simultaneous-integrated boost
radiotherapy of left-sided breast cancer after breast-conserving surgery. A total
of nine patients with stage I, left-sided breast cancer who underwent breast
conserving surgery were selected for this retrospective study. For each patient,
a hybrid arc plan was generated and then compared with two hybrid intensity
modulated radiotherapy plans. All plans were optimized using the same objectives
and dose constraints. The prescription dose was 50.4 Gy to the planning target
volume with simultaneous boost to 60 Gy to the expanded gross target volume in 28
fractions. The differences among these hybrid plans were analyzed by the
Kolmogorov-Smirnov test or the Wilcoxon rank sum test. The hybrid arc plans
achieved the clinical requirements of target dose coverage and normal tissue (NT)
dose constraints. It was found that the hybrid arc plans showed advantages in the
conformity index of the expanded gross target volume, the V5 of the heart, the D2
of the left ventricle, and the D2 and V50.4 of NTs. The average beam-on time and
monitor units of the hybrid arc plans were significantly lower (P < 0.001).
PMID- 28405102
TI - Measurement of Total Scatter Factor for Stereotactic Cones with Plastic
Scintillation Detector.
AB - Advanced radiotherapy modalities such as stereotactic radiosurgery (SRS) and
image-guided radiotherapy may employ very small beam apertures for accurate
localized high dose to target. Accurate measurement of small radiation fields is
a well-known challenge for many dosimeters. The purpose of this study was to
measure total scatter factors for stereotactic cones with plastic scintillation
detector and its comparison against diode detector and theoretical estimates.
Measurements were performed on Novalis TxTM linear accelerator for 6MV SRS beam
with stereotactic cones of diameter 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm. The
advantage of plastic scintillator detector is in its energy dependence. The total
scatter factor was measured in water at the depth of dose maximum. Total scatter
factor with plastic scintillation detector was determined by normalizing the
readings to field size of 10 cm * 10 cm. To overcome energy dependence of diode
detector for the determination of scatter factor with diode detector, daisy
chaining method was used. The plastic scintillator detector was calibrated
against the ionization chamber, and the reproducibility in the measured doses was
found to be within +/- 1%. Total scatter factor measured with plastic
scintillation detector was 0.728 +/- 0.3, 0.783 +/- 0.05, 0.866 +/- 0.55, 0.885
+/- 0.5, and 0.910 +/- 0.06 for cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and
15 mm, respectively. Total scatter factor measured with diode detector was 0.733
+/- 0.03, 0.782 +/- 0.02, 0.834 +/- 0.07, 0.854 +/- 0.02, and 0.872 +/- 0.02 for
cone sizes of 6 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm, respectively. The
variation in the measurement of total scatter factor with published Monte Carlo
data was found to be -1.3%, 1.9%, -0.4%, and 0.4% for cone sizes of 7.5 mm, 10
mm, 12.5 mm, and 15 mm, respectively. We conclude that total scatter factor
measurements for stereotactic cones can be adequately carried out with a plastic
scintillation detector. Our results show a high level of consistency within our
data and compared well with published data.
PMID- 28405103
TI - Comparison of Rapid Arc and Intensity-modulated Radiotherapy Plans Using Unified
Dosimetry Index and the Impact of Conformity Index on Unified Dosimetry Index
Evaluation.
AB - The aim of this study was to evaluate the impact of conformity index in the
unified dosimetry index (UDI) score for two different planning techniques namely
intensity-modulated radiotherapy (IMRT) and Rapid Arc. Rapid Arc and IMRT plans
of 57 patients were evaluated and compared using UDI score which incorporates
four indices. To determine the impact of conformity index on the IMRT and Rapid
Arc plans, UDI at conformity index one of all plan (UDIunit_CI) score was
calculated by assuming conformity index is equal to one. Mean and standard
deviations of all indices were calculated. Rapid Arc technique plans of different
treatment sites of all patients scored lesser UDI than IMRT plans, and the
conformity index of Rapid Arc plan was significantly better than IMRT plan. The
average dose gradient, homogeneity, coverage, and conformity index of all sites
with Rapid Arc plans were 0.212 +/- 0.05, 1.123 +/- 0.03, 0.959 +/- 0.03, and
1.056 +/- 0.09; with IMRT plans were 0.190 +/- 0.05, 1.113 +/- 0.04, 0.950 +/-
0.04, and 1.172 +/- 0.16, respectively. UDI score value with actual conformity
index of Rapid Arc and IMRT plans differed significantly (P < 0.001). However,
UDIunit_CI score values with assumed conformity index equal to one did not differ
significantly (P = 0.528). In the comparison of IMRT and Rapid Arc plans using
the UDI score, the impact of conformity index was significant.
PMID- 28405104
TI - Structural Shielding Design of a 6 MV Flattening Filter Free Linear Accelerator:
Indian Scenario.
AB - Detailed structural shielding of primary and secondary barriers for a 6 MV
medical linear accelerator (LINAC) operated with flattening filter (FF) and
flattening filter free (FFF) modes are calculated. The calculations have been
carried out by two methods, one using the approach given in National Council on
Radiation Protection (NCRP) Report No. 151 and the other based on the monitor
units (MUs) delivered in clinical practice. Radiation survey of the installations
was also carried out. NCRP approach suggests that the primary and secondary
barrier thicknesses are higher by 24% and 26%. respectively, for a LINAC operated
in FF mode to that of a LINAC operated in both FF and FFF modes with an
assumption that only 20% of the workload is shared in FFF mode. Primary and
secondary barrier thicknesses calculated from MUs delivered on clinical practice
method also show the same trend and are higher by 20% and 19%, respectively, for
a LINAC operated in FF mode to that of a LINAC operated in both FF and FFF modes.
Overall, the barrier thickness for a LINAC operated in FF mode is higher about
20% to that of a LINAC operated in both FF and FFF modes.
PMID- 28405106
TI - Evaluation of Intensity Modulated Radiation Therapy Delivery System using a
Volumetric Phantom on the Basis of the Task Group 119 Report of American
Association of Physicists in Medicine.
AB - The current work describes the implementation of the American Association of
Physicists in Medicine (AAPM)'s Task Group 119 report on a volumetric phantom
(Delta4, Scandidos, Uppsala, Sweden) following the stated dose goals, to evaluate
the step-and-shoot intensity modulated radiation therapy (IMRT) system. Delta4
consists of diode detectors, lying on two crossed planes, measuring the delivered
dose, and providing two-dimensional dosimetric information. Seven plans of
different goals and complexity were performed, with individual structure sets.
TG199 structure sets and plans were transferred and implemented on the Delta4
phantom taking into account its cylindrical geometry. All plans were delivered
with a 6 MV linear accelerator equipped with multileaf collimator of 1 cm
thickness. Plan results for each test met the recommended dose goals. The
evaluation was performed in terms of dose deviation, distance to agreement, and
gamma index passing rate. In all test cases, the gamma index passing rate was
measured >90%. Delta4 phantom has proven to be fast, applicable, and reliable for
the step-and-shoot IMRT commissioning following TG119's recommended tests.
Although AAPM's TG119 report is referring to the implementation of test plans
that do not correspond to patient plans, it could be used as an evaluation tool
of various IMRT systems, considering the local treatment planning system and the
delivery system.
PMID- 28405105
TI - Hesperidin as Radioprotector against Radiation-induced Lung Damage in Rat: A
Histopathological Study.
AB - Reactive oxygen species (ROS) are generated by ionizing radiation, and one of the
organs commonly affected by ROS is the lung. Radiation-induced lung injury
including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy
(RT) of patients with thorax irradiation. Administration of antioxidants has been
proved to protect against ROS. The present study was aimed to assess the
protective effect of hesperidin (HES) against radiation-induced lung injury of
male rats. Fifty rats were divided into three groups. G1: Received no HES and
radiation (sham). G2: Underwent gamma-irradiation to the thorax. G3: Received HES
and underwent gamma-irradiation. The rats were exposed to a single dose of 18 Gy
using cobalt-60 unit and were administered HES (100 mg/kg) for 7 days before
irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT.
Histopathological results in 24 h showed radiation-induced inflammation and
presence of more inflammatory cells as compared to G1 (P < 0.05). Administration
of HES significantly decreased such an effect when compared to G2 (P < 0.05).
Histopathological evaluation in 8 weeks showed a significant increase in mast
cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness,
pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05). HES
significantly decreased inflammatory response, fibrosis, and mast cells when
compared to G2 (P < 0.05). Administration of HES resulted in decreased radiation
pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study
showed HES to be an efficient radioprotector against radiation-induced damage in
the lung of tissue rats.
PMID- 28405107
TI - Response of Nanodot Optically Stimulated Luminescence Dosimeters to Therapeutic
Electron Beams.
AB - Response of Al2O3:C-based nanoDot optically stimulated luminescence (OSL)
dosimeter was studied for the dosimetry of 6, 9, 12, 16, and 20 MeV therapeutic
electron beams. With reference to ionization chamber, no change in the response
was observed with the change in the energy of electron beams for the field size
from 6 cm * 6 cm to 25 cm * 25 cm, dose rates from 100 MU/min to 600 MU/min, and
the linearity in the response up to 300 cGy. The fading of the transient signal
was higher for 20 MeV electron beam than that of 6 MeV electron beam by about 5%
as compared to value at 20 min after irradiation. The depletion of OSL signal per
readout in 200 successive readouts was also found to change with dose and energy
of electron beam from 6 MeV (9% and 12% per readout at 2 and 10 Gy, respectively)
to 20 MeV (9% and 16% at 2 and 10 Gy, respectively). The OSL sensitivity changed
in the range from 2% to 6% with accumulated doses from 2 to 8 Gy and with
electron energy from 6 to 20 MeV, but the sensitivity could be reset using an
optical annealing treatment. Although negligible fading for postirradiation
storage from 20 min to several months, acceptable precision and linearity in the
desired range, and high reproducibility makes nanoDot dosimeters very attractive
for the dosimetry of therapeutic electron beams, a note should be made for
changes in sensitivity at doses beyond 2 Gy and electron beams energy dependence
in reuse, short-term fading, and signal depletion on repeated readout.
PMID- 28405108
TI - Assessment of Regional Pediatric Computed Tomography Dose Indices in Tamil Nadu.
AB - The aim of this article is to assess Tamil Nadu pediatric computed tomography
(CT) diagnostic reference levels (DRLs) by collecting radiation dose data for the
most commonly performed CT examinations. This work was performed for thirty CT
scanners installed in various parts of the Tamil Nadu region. The patient cohort
was divided into two age groups: <1 year, and 1-5 years. CT dose indices were
measured using a 10 cm3 pencil ion chamber with pediatric head and body
polymethyl methacrylate phantoms. Dose data such as volumetric CT dose index
(CTDIv) and dose length product (DLP) on a minimum of twenty average-sized
pediatric patients in each category were recorded to calculate a mean site CTDIv
and DLP value. The rounded 75th percentile was used to calculate a pediatric DRL
for each hospital, and then region by compiling all results. Data were collected
for 3600 pediatric patients. Pediatric CT DRL for two age groups: <1 year (CTDIv
and DLP of head [20 mGy, 352 mGy.cm], chest [7 mGy, 120 mGy.cm] and abdomen [12
mGy, 252 mGy.cm]), and 1-5 years (CTDIv and DLP of head [38 mGy, 505 mGy.cm],
chest [8 mGy, 132 mGy.cm] and abdomen [14 mGy, 270 mGy.cm]) for select procedures
have been calculated. Proposed pediatric DRLs of CTDIv and DLP for head procedure
were lower, and for chest and abdomen procedures were higher than European
pediatric DRLs for both age groups.
PMID- 28405110
TI - Issue of "In Water Calibration Certificate" for Cobalt-beam Quality at 10 cm
Reference Depth - Is it Admissible Under TRS 398 Protocol?
PMID- 28405109
TI - Bystander Effect and Second Primary Cancers following Radiotherapy: What are its
Significances?
PMID- 28405111
TI - Erratum: Clinical Implications of Eclipse Analytical Anisotropic Algorithm and
Acuros XB Algorithm for the Treatment of Lung Cancer.
AB - [This corrects the article on p. 219 in vol. 41, PMID: 28144113.].
PMID- 28405112
TI - What Does It Take to Get Published?
PMID- 28405113
TI - A New Dawn for Intrauterine Insemination: Efficient and Prudent Practice will
Benefit Patients, the Fertility Industry and the Healthcare Bodies.
AB - This review addresses the misplaced facts about the IUI procedure within a
lucrative fertility industry. Evidence suggests IUI must be a first-line
treatment option for most couples except in cases of bilateral tubal blockage and
severe oligozoospermia. We introduce the concept of using 'consecutive
ejaculation' in men with subfertility and one which can radically alter the male
infertility definition, thereby providing a new approach to examining and
managing male factor infertility. The review also explores various aspects
affecting the IUI procedure, its determinants of success, risks and areas for
future improvements. Areas such as choice of patients, clinical management of
patients, the type of stimulation regime, timing and the management of sperm
usage have significant bearing to whether IUI will succeed. The paper asserts
that IUI should be the first choice of fertility treatment.
PMID- 28405114
TI - Advances in the SUI Surgeries.
AB - Stress urinary incontinence is a condition associated with advancing age and high
parity. Millions of women all over the world have suffered, in silence,
embarrassment and social isolation due to this condition. Over the years, several
operative procedures have evolved for correction of urinary incontinence with
many of them having poor success or high recurrence rates over long-term period.
This mini review covers various surgical procedures evolved over the last couple
of years and recent advances in the management of urinary incontinence.
PMID- 28405115
TI - Acceptance of Contraceptive Methods Among Postpartum Women in a Tertiary Care
Center.
AB - BACKGROUND: In India, a large proportion of women with an unmet need for
contraception are within their first year after childbirth. Therefore,
concentrating efforts to educate postpartum women on the importance of attending
contraceptive clinics could have a proportionally bigger impact on increasing
postpartum contraception usage. METHODS: Hundred and seventy-eight (178) women
were followed up to determine the proportion of postpartum women who attended the
family planning clinics for contraceptive counseling. The reason for non
attendance, choice and effectiveness of contraceptive method selected was
determined. RESULTS: Out of 178 postpartum women who were followed up, only 12
(6.8 %) attended the contraceptive clinic. IUD, POPs and Inj-DMPA are the
preferred contraceptive methods selected by postpartum women. Hundred percent of
the postpartum women who attended contraceptive selected a contraceptive method
as compared to only 44 % of the postpartum women who did not attend a
contraceptive clinic. Only 29.2 % of these postpartum women selected highly
effective contraceptive methods as compared to 83.3 % by the postpartum women who
attended family planning clinics. The common reasons cited for not attending
contraceptive clinic was found to be time constraint (43.9 %) followed by 'stay
far away' (39 %), followed by 'already have information' (9.7 %). CONCLUSIONS:
Family planning service that is scheduled to be delivered at the 6-week
postpartum is rarely attended. The common reason cited by postpartum women for
poor attendance in these family planning clinics was time constraint.
PMID- 28405116
TI - Oral Misoprostol Solution for Induction of Labour.
AB - OBJECTIVE: To determine the effects of oral misoprostol solution for induction of
labour. STUDY DESIGN: This is a prospective observational study. SETTING: This
study was conducted in Government Medical College, Aurangabad. METHOD: Patients
undergoing induction of labour after 36 weeks of pregnancy were allocated by
randomization to induction of labour with oral misoprostol solution administered
2 h apart. Delivery within 24 h after induction with oral misoprostol solution
was the primary outcome on which the sample size was based. The data were
analysed by Statistical Software for Social Sciences software. RESULT: Two
hundred patients were randomly selected for induction with oral misoprostol
solution. There were no significant differences in substantive outcomes. Vaginal
delivery within 24 h was achieved in 80.5 % of patients. The caesarean section
rate was 19.5 %. Uterine hyperactivity occurred in 4 % of patients. The response
to induction of labour in women with unfavourable cervices (modified Bishop's
score <2) was somewhat slower with misoprostol, induction to delivery interval
was more, oxytocin requirement was more, and vaginal delivery rate was less.
CONCLUSION: This new approach to oral misoprostol solution administration was
successful in achieving vaginal delivery rate in 24 h in 80.5 % of patients; rate
of LSCS was less 19.5 %.
PMID- 28405117
TI - Oligoamnios and Perinatal Outcome.
AB - OBJECTIVES: We aimed at evaluating the predictive value of amniotic fluid index
<=5 on perinatal outcome in terms of effect on cardiotocography, mode of
delivery, meconium in liquor, birth weight, fetal distress, APGAR score at birth
and neonatal admission to ICU. METHODS: This is a prospective study of 308
antenatal women admitted to labor ward of MIMS during February 2014-December 2015
with gestational ages between 34 and 41 weeks. All women enrolled were subjected
to history taking, examination, AFI estimation and compared between those with
AFI <=5 from rest. RESULTS: The non-reactive CTG, cesarean section rate due to
fetal distress, low birth weight, APGAR score <7 and NICU admission were
significantly high among those with oligoamnios than the control group.
CONCLUSION: Oligoamnios has a significant correlation with adverse perinatal
outcome.
PMID- 28405118
TI - Estimation of Serum Uric Acid as an Indicator of Severity of Preeclampsia and
Perinatal Outcome.
AB - BACKGROUND: Uric acid is a marker of oxidative stress tissue injury and renal
dysfunction, hence a correlation hypothesized. OBJECTIVES: (1) To evaluate
severity of preeclampsia with raised serum uric acid. (2) To evaluate perinatal
outcome in preeclampsia with raised serum uric ccid. MATERIALS AND METHODS: 50
pregnant women with severe preeclampsia and 50 normotensive women were included
in the study and maternal serum uric acid was estimated in both the groups.
RESULTS: In the study group comprising of 50 cases of preeclampsia, there is a
positive correlation (r = 0.695 & +0.359) between the variables in study group,
and as the SBP or DBP increases, the MSUA concentration also increases. In
control group, there is a negative correlation (r = -0.083 & -0.095). Perinatal
complication was more in study group, 54 % were preterm compared to 4 % in
control group also as MSUA value increased average gestational age decreased.
Mean birth weight in study group was 1.8 kg study group of which 13 (26 %) babies
were VLBW, 28 (56 %) were LBW, and 9 (18 %) babies had normal birth weight, in
control group mean birth weight was 2.99 kg. There were 6 cases of ELBW babies in
study group which were included in VLBW group for statistical calculation. The
difference was found to be statistically significant (p < 0.05). In the study
group, the MSUA concentration is found higher in LBW and VLBW babies compared to
normal birth weight babies. CONCLUSION: There is a positive correlation between
SUA & severity of preeclampsia, and a significant adverse fetal outcome is
observed with raised MSUA in preeclamptic patients.
PMID- 28405119
TI - FIGO's PALM-COEIN Classification of Abnormal Uterine Bleeding: A Clinico
histopathological Correlation in Indian Setting.
AB - INTRODUCTION: Abnormal uterine bleeding (AUB) is the commonest menstrual problem
during perimenopause. The International Federation of Gynaecology and Obstetrics
working group on menstrual disorders has developed a classification system (PALM
COEIN) for causes of the AUB in non-gravid women. The present study was conducted
with the aim to study the two components of this system in clinical practice in
general and to establish a clinico-pathological correlation of AUB with context
of PALM component in particular. MATERIALS AND METHODS: Two hundred and thirty
six perimenopausal women (aged 40 years and above till 1 year beyond menopause)
admitted with complaints of abnormal uterine bleeding were studied. After
thorough history and examination, a clinical diagnosis was made as per PALM-COEIN
classification. Relative contribution of various causes of PALM (structural) and
COEIN (functional) components was analysed. After all indicated investigations,
endometrial sampling and hysterectomy specimen were assessed by histology. A
clinicopathological correlation was analysed statistically. RESULT: PALM and
COEIN components contributed almost equally for AUB when assessed clinically. On
the other hand, the histological examination revealed significantly more cases of
PALM (structural or anatomical) component of AUB, i.e. 50.23 versus 63.98 % (p <=
0.05) The difference was mainly attributed to the detection of more cases of AUB
M (malignancy and hyperplasia) in highly significant proportions (p <= .01) and
coexistent cases of AUB-A;L. AUB-L was the commonest (41.1 %) aetiology overall.
CONCLUSION: The PALM-COEIN classification system should take into account both
the clinical and histopathological diagnoses in women having AUB around
perimenopause as the two diagnostic modalities are complementary to each other
and clinical impression should be placed into proper perspective of this
classification in order to optimise outcome.
PMID- 28405120
TI - Fractionated Palliative Pelvic Radiotherapy as an Effective Modality in the
Management of Recurrent/Refractory Epithelial Ovarian Cancers: An Institutional
Experience.
AB - BACKGROUND: The advent of effective chemotherapeutic agents for ovarian carcinoma
has made radical abdomino-pelvic radiation redundant. Nevertheless, palliative
pelvic radiotherapy still has a role in palliating local symptoms. However, its
effect on progression-free survival (PFS) may be debated. AIMS: To study the
outcome of fractionated palliative pelvic radiotherapy in relapsed ovarian
cancers in terms of symptom control and PFS. METHODS: Twenty-three patients of
ovarian cancers, heavily pretreated with chemotherapy and with recurrent or
residual pelvic masses, were planned for palliative pelvic radiotherapy to the
dose of 46-50 Gy in 23-25 fractions in 4.5-5 weeks. Symptom control and outcomes
have been analyzed. RESULTS: Post-radiotherapy, abdominal pain was controlled in
15 out of 17 patients (88.2 %), bleeding per vaginum in all 5 patients and
vaginal discharge stopped in 4 out of 5 patients (80 %). On follow-up, of 23
patients, 17 (74 %) had progressive disease post-radiation, and median time to
disease progression was 10 months (range 1-49). On univariate analysis, increased
PFS was observed in patients who received radiation late in their course of
disease, those with serous histology, and with lesser disease bulk in pelvis (<=2
cm) prior to radiation initiation. CONCLUSION: Fractionated palliative pelvic
radiotherapy is an efficient method for symptom palliation in relapsed ovarian
cancers. Patients who are heavily pretreated with chemotherapy and have a small
volume pelvic disease may show a prolonged PFS with addition of pelvic
radiotherapy. Indications of radiotherapy, however, need to be defined.
PMID- 28405121
TI - GnRh Agonist Treatment Improves Implantation and Pregnancy Rates of Frozen-Thawed
Embryos Transfer.
AB - OBJECTIVE: To study the effect of GnRh agonist administration prior to estrogen
progesterone preparation of the endometrium on the implantation rate in frozen
thawed embryo transfer (FET) cycles in infertile patients treated with IVF/ICSI.
DESIGN: Prospective controlled study. SETTING: Private center in Alexandria,
Egypt. PATIENTS: Patients undergoing frozen-thawed embryo transfer FET.
INTERVENTIONS: Patients were divided into two groups, A and B. Group A patients
consisted of 110 patients (110 cycles) who received daily subcutaneous injections
of 0.1 mg of the GnRh agonist triptorelin starting from the mid-luteal phase of
the cycle preceding the actual FET cycle. The dose was reduced to 0.05 mg from
the second day of the cycle when daily oral estradiol valerate 6 mg was also
started. Daily vaginal supplementation of micronized progesterone 400 mg b.d. was
started after 12 days when the GnRh agonist was also stopped. Frozen-thawed
embryos were transferred on day + 1 of their chronological age and when the
endometrium reached 12 mm in thickness. Group B consisted of 100 patients (100
cycles) who started daily estradiol valerate 6 mg administration from the second
day of the FET cycle and followed the same regimen but without prior treatment
with triptorelin. MAIN OUTCOME MEASURES: Implantation and pregnancy rates were
compared among the two groups. RESULTS: There was a significant increase in
implantation rate in the GnRh agonist group (group A) compared to the estrogen
and progesterone only group (group B) (44.1 vs. 21.1 %; P = 0.002*). The
pregnancy rate was also significantly higher in group A compared to group B (65.5
vs. 42 %, P = 0.013*). CONCLUSIONS: GnRh agonist administration during
endometrial preparation for FET increases the implantation and pregnancy rates.
PMID- 28405122
TI - Evaluation of Dehydroepiandrosterone Supplementation on Diminished Ovarian
Reserve: A Randomized, Double-Blinded, Placebo-Controlled Study.
AB - INTRODUCTION: We conducted a randomized, double-blinded, placebo-controlled
study, to evaluate the effect of dehydroepiandrosterone (DHEA), on diminished
ovarian reserve (DOR). MATERIALS AND METHODS: Twenty patients with DOR received
DHEA (oral 25 mg three times a day). Post-supplementation 12 weeks, D2/3 age
specific follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH) levels,
and antral follicle count (AFC), were repeated to evaluate response. Spontaneous
pregnancy rates and regularization of menstrual cycles were also studied as
secondary outcome. RESULTS: Predominant risk factors were age >35 years (28 %)
and poor responders to ovarian stimulation (23 %). There was significant
improvement of AMH levels (1.15 +/- 1.49 vs. 1.53 +/- 1.62) found before and
after supplementation in the DHEA group. When the AMH values between DHEA and
placebo group were compared, pre- and post-supplementation, no significant
difference was found. There was decrease in FSH levels and increase in AFC value
post-supplementation in both DHEA and placebo groups which was not statically
significant. DHEA supplementation benefited clinically, as evidenced by the
improvement in the menstrual abnormality spontaneous conception in two cases
each. CONCLUSIONS: A significant improvement in AMH levels pre- and post
supplementation of DHEA was noted. The same was not seen for FSH and AFC values.
PMID- 28405123
TI - Maternal Near-Miss: A Perimortem Caesarean Section Resulting in a Remarkable
Foetomaternal Recovery in a Rural Tertiary Care Centre in Eastern India.
PMID- 28405124
TI - Leiomyoma of Urinary Bladder in Middle-Aged Female.
PMID- 28405125
TI - Panicker's Vacuum Suction Haemostatic Device for Treating Post-Partum
Haemorrhage.
PMID- 28405126
TI - Nutritional, Medicinal and Toxicological Attributes of Star-Fruits (Averrhoa
carambola L.): A Review.
AB - Plants are very complex organisms that produce medicinally important natural
products. The Star-fruit producing plant (Averrhoa carambola L.) is a species of
woody plant in the family Oxalidaceae native to the Philippines, Indonesia,
Malaysia, Vietnam, India, Bangladesh and Sri Lanka; but, cultivated in many parts
of the world. Star-fruits are popular tropical fruits and used commonly in
Ayurvedic and Traditional Chinese Medicines (TCM) in India, China, and Brazil to
relieve ailments such as chronic headache, fever, cough, gastro-enteritis,
diarrhoea, ringworm infections, and skin inflammations. However, this fruit
contains high amount of oxalate, which is hazardous for uremic patients, and
caramboxin (CBX), which is neurotoxic. The aim of this review is to highlight the
nutritional, medicinal and toxicological traits of the star-fruits.
PMID- 28405128
TI - Eminence or Evidence? The Volatility, Uncertainty, Complexity, and Ambiguity in
Healthcare.
PMID- 28405127
TI - Molecular docking analysis of UniProtKB nitrate reductase enzyme with known
natural flavonoids.
AB - The functional inference of UniProtKB nitrate reductase enzyme (UniProtKB -
P0AF33) through structural modeling is of interest in plant biology. Therefore, a
homology model for UniProtKB variant of the enzyme was constructed using
available data with the MODELER software tool. The model was further docked with
five natural flavonoid structures such as hesperetin, naringenin, leucocyanidin,
quercetin and hesperetin triacetate using the AUTODOCK (version 4.2) software
tool. The structure aided molecular interactions of these flavonoids with nitrate
reductase is documented in this study. The binding features (binding energy
(DeltaG) value, H bonds and docking score) hesperetin to the enzyme model is
relatively high, satisfactory and notable. This data provides valuable insights
to the relative binding of several naturally occurring flavonoids to nitrate
reductase enzyme and its relevance in plant biology.
PMID- 28405129
TI - Effect of Addition of Fentanyl and Clonidine to Local Anesthetic Solution in
Peribulbar Block.
AB - OBJECTIVE: To compare the effect of addition of fentanyl and clonidine as
adjuvants to bupivacaine and lignocaine in peribulbar block. METHODS: The study
was conducted on 105 adult patients of either sex, of ASA grade I and II
undergoing ophthalmic surgeries. Patients were randomly divided into 3 groups of
35 each. All the patients were given peribulbuar block with 5ml lignocaine 2% +3
ml bupivacaine 0.5% +1 ml hyaluronidase (250 IU). In addition to this 1 ml normal
saline was added to Group S, 25 MUg fentanyl to Group F and 25 MUg clonidine to
Group C. Onset and duration of globe and lid akinesia, duration of sensory
blockage and analgesia, hemodynamic parameters, number of rescue analgesic and
visual analogue score were recorded. RESULTS: The mean time of onset of globe and
lid akinesia was significantly faster in group F and group C compared to group S,
mean duration of globe and lid akinesia was longer in Group F (207.71 + 13.54 and
143.14 + 7.86 min) and group C (213.52 + 14.52 and 162.06 + 17.1 min) compared to
group S (117.78 + 10.42 and 87.64 + 9.76 min). The mean duration of analgesia was
significantly longer in group F (217.71 + 12.67) and C (258.82 + 14.50 min) as
compared to group S (131.39 + 9.63 min). CONCLUSION: Addition of fentanyl or
clonidine as adjuvant to local anaesthetic in peribulbar block provides faster
onset and prolonged analgesia compared to local anaesthetic alone.
PMID- 28405131
TI - Indocyanine Green-001 (ICG-001) Attenuates Wnt/beta-catenin-induces Myocardial
Injury Following Sepsis.
AB - OBJECTIVE: To investigate the mechanistic pathway of both indocyanine green (ICG)
001 in attenuated endotoxemia-induced cardiac depression through downregulation
cardiac Wnt/ beta-catenin cell signaling. MATERIALS AND METHODS: Adult (4-6
months) male Albino-Webster mice, their weights ranged from 25 to 30 g, were
pretreated with ICG-001 i.p., following cecal ligation and puncture (CLP). Left
ventricle (LV) function was assessed using a microcatheter system. Monocyte
chemoattractant protein-1 (MCP-1) and cytokines mediators in plasma and
myocardium were analyzed by enzyme-linked immunosorbent assay. Further, the
cardiac Wnt protein measured by quantitative real-time polymerase chain reaction
while beta-catenin analysis through Western blotting procedure. The pathological
changes and cells injury in the myocardium were examined using hematoxylin and
eosin staining. RESULTS: CLP mice displayed worse LV function. The exaggerated
cardiac depression in CLP mice was associated with higher levels of MCP-1 and
cytokines in plasma and myocardium together with greater cardiac levels of
cardiac troponin-I and Wnt/beta-catenin. Neutralization of sepsis by either ICG
001resulted in improved LV function and reductions in inflammatory mediators.
CONCLUSION: Taken together, these data showed that ICG-001 improved LV function
following sepsis through downregulation of Wnt/beta-catenin and serve as a
potential mechanistic pathway ICG-001 in therapeutic cardiac endotoxemia in
animal model.
PMID- 28405130
TI - Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney
Failure Mouse Model.
AB - OBJECTIVE: To investigate the relationship between renal function and linezolid
(LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a
chronic renal disease (CRD) mouse model. MATERIALS AND METHODS: CRD was induced
in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy.
After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally
once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and
hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq)
was administrated intravenously to LZD-administered mice to evaluate the
thymidine uptake ability of bone marrow. RESULTS: Platelet counts were
significantly lower in the LZD-administered CRD group than in the LZD
nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes
were not observed in LZD-administered mice with normal renal function, regardless
of the duration of LZD administration. No significant changes were observed in
WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive
levels in bone marrow were not significantly different in each group.
CONCLUSIONS: These results indicate that LZD-induced decreases in platelet counts
were enhanced by renal impairment in vivo, suggesting that LZD-induced
thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression.
PMID- 28405132
TI - Antianginal Efficacy and Tolerability of Ranolazine as an Add-on Drug to
Concomitant Medications Primarily Metoprolol in Chronic Stable Angina Patients: A
Prospective, Open-Label Study.
AB - OBJECTIVE: To evaluate the efficacy and tolerability of ranolazine as an add-on
drug in chronic stable angina patients and the impact of ranolazine on the
quality of life in chronic stable angina patients receiving other antianginal
medications. MATERIALS AND METHODS: It was a prospective, open-label, hospital
based study involving 144 patients with chronic stable angina. First group
received either metoprolol 12.5 or 25 mg/day or other antianginal medications; if
the symptoms persist, the dose of metoprolol was increased to 50 mg/day, and to
the second group, ranolazine 500 mg BD or 1 g OD was added along with metoprolol
or others if the anginal attacks were not subsiding. The patients were followed
up to 6 months with electrocardiography, treadmill test, and quality of life
questionnaire. Adverse events were recorded at each visit during the study.
RESULTS: There was a statistically significant reduction in weekly anginal
frequency (P < 0.001) and improvement in an exercise tolerance in both the
groups, but more in the ranolazine group. Adverse events reported were mild,
infrequent. CONCLUSION: Ranolazine is could be used as an add-on drug in chronic
angina patients not improved with metoprolol or antianginal medications.
PMID- 28405134
TI - Methylcobalamin in Vitamin B12 Deficiency: To Give or not to Give?
PMID- 28405133
TI - Risperidone-Induced Adverse Drug Reactions and Role of DRD2 (-141 C Ins/Del) and
5HTR2C (-759 C>T) Genetic Polymorphisms in Patients with Schizophrenia.
AB - OBJECTIVE: To determine the adverse drug reaction (ADR) profile of risperidone
and their association with dopamine (DRD2 - 141 C Ins/Del/rs1799732) and
serotonin receptor (5HTR2C -759 C>T/rs3813929) gene polymorphisms in patients
with schizophrenia. MATERIALS AND METHODS: The study was conducted among 289
patients who were diagnosed with schizophrenia and were on treatment with
risperidone (4-8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was
carried by real-time quantitative polymerase chain reaction. All the patients
were observed for the occurrences of ADRs during the study. Changes in prolactin
levels and body weight were analyzed for a subgroup of 102 and 97 patients,
respectively. RESULTS: Risperidone-induced extrapyramidal symptoms (EPSs) were
seen in 36.7% of patients. Among them, tremors were the most common symptom
31.8%. Risperidone-induced hyperprolactinemia and weight gain were seen in 87.2%
and 53.6% in subgroup patients. Adverse effects such as sedation,
gastrointestinal effects, and amenorrhea were seen in 9.7% (28/289), 5.1%
(15/289), and 6.1% (7/114), respectively. Occurrence of DRD2 - 141 Ins/Del and
Del/Del polymorphisms were significantly associated with increased prolactin
levels in response to risperidone (odds ratio [OR] = 10.45; 95% confidence
interval = 1.29-84.89, P = 0.004). No such association was observed with 5HTR2C (
759 C>T) polymorphism. Weight gain and EPS were not associated with the above
genetic polymorphisms. CONCLUSION: Hyperprolactinemia, weight gain, and EPSs
(>36.7%) were common adverse effects of risperidone. DRD2 - 141C Ins/Del and
Del/Del polymorphisms were significantly associated with increased prolactin
levels (OR = 10.45) in response to risperidone.
PMID- 28405135
TI - Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of
the Digestive Tract Associated with Leflunomide and Low-dose Methotrexate
Combination Therapy.
AB - A 60-year-old male patient developed hyperpyrexia, cough, expectoration with
blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving
35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate
(MTX) for active rheumatoid arthritis. On admission, routine blood tests showed
severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration
compared with the relatively normal results of 1 month previously during the
first hospitalization. Chest radiography revealed inflammation in both lungs, and
a fecal occult blood test was positive. Given this presentation, severe bone
marrow suppression accompanying pulmonary infection and hemorrhage of the
digestive tract associated with LEF and MTX combination therapy was diagnosed.
After 28 days of symptomatic treatment, the patient's complications subsided
gradually. This case highlighted that bone marrow suppression associated with MTX
and LEF combination therapy could be very serious, even at a normal dose or
especially at the beginning of treatment. MTX and LEF combination therapy should
be used with caution or be limited in those with a history of pulmonary disease,
hemorrhage of the digestive tract, or other relevant diseases.
PMID- 28405136
TI - Ifosfamide-induced Encephalopathy Precipitated by Aprepitant: A Rarely Manifested
Side Effect of Drug Interaction.
AB - Central nervous system (CNS) toxicity has been reported in approximately 10%-30%
of patients receiving intravenous infusions of ifosfamide. Encephalopathy is a
rare but serious CNS adverse reaction in these patients, and although usually
transient and reversible, may cause persistent neurological dysfunction or death.
Clinical features range from fatigue and confusion to coma and death. Ifosfamide
forms backbone of various treatment regimens including curative treatment and
palliative chemotherapy regimen. Precipitation of ifosfamide-induced
encephalopathy (IIE) by aprepitant has been reported in the literature rarely.
Ifosfamide is moderately emetogenic; hence, aprepitant is used to prevent emesis
induced by ifosfamide. We here report a case where a patient of recurrent B-cell
Philadelphia-negative acute lymphoblastic lymphoma was given aprepitant to
prevent ifosfamide-induced emesis. After 24 h of ifosfamide infusion, the patient
developed symptoms of encephalopathy, i.e., headache, vomiting, and one episode
of seizure which was followed by disoriented behavior. After doing all routine
investigations and neuroimaging, the diagnosis of IIE was kept on clinical
grounds, and after looking for the various factors, we came across injection
fosaprepitant as the precipitating factor. On the clinical grounds, the patient
was treated with hydration and injection methylene blue for above complaints, and
the patient recovered without any residual deficit within 48-72 h. Hence, in the
presence of causative agent, i.e., ifosfamide and precipitating agent injection
fosaprepitant with negative imaging and normal laboratory parameters as well as
the early and good response to methylene blue, the diagnosis of IIE precipitated
by aprepitant was confirmed.
PMID- 28405137
TI - Pleural Tuberculosis following Infliximab Therapy for Ankylosing Spondylitis.
AB - We present a case of pleural tuberculosis (TB) in a patient on infliximab for
ankylosing spondylitis. A 36-year-old male presented to our hospital with low
back ache of inflammatory type along with multiple symmetric inflammatory type of
joint pain. Further clinical examination, laboratory and radiological
investigations were suggestive of ankylosing spondylitis. He was initially
treated with nonsteroidal anti-inflammatory drugs but citing poor response it was
decided to initiate biologic therapy using infliximab (antitumor necrosis factor
alpha). Mantoux test and chest radiograph were done before the therapy to rule
out TB. Following three doses of infliximab, patient came with complaints of
fever and cough for 1 week. On investigation, it was found to be a case of
pulmonary TB. This shows the importance of close monitoring of patient for TB
among patients on infliximab even though the screening test has come out to be
negative.
PMID- 28405138
TI - Long term follow-up and outcome of liver transplantation from hepatitis B surface
antigen positive donors.
AB - Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes:
it allows to rescue patients with an HBV-related advanced liver disease,
resulting in a demographical modification of the waiting list for liver
transplant. In an age of patient-tailored treatments, in liver transplantation as
well the aim is to offer the best suitable graft to the patient who can benefit
from it, also expanding the criteria for organ acceptance and allocation. With
the intent of developing strategies to increase the donor pool, we set-up a
multicenter study involving 3 Liver Transplant Centers in Italy: patients
undergoing liver transplantation between March 03, 2004, and May 21, 2010, were
retrospectively evaluated. 1408 patients underwent liver transplantation during
the study period, 28 (2%) received the graft from hepatitis B surface antigen
positive (HBsAg)-positive deceased donors. The average follow-up after liver
transplantation was 63.7 mo [range: 0.1-119.4; SD +/- 35.8]. None Primary non
function, re-liver transplantation, early or late hepatic artery thrombosis
occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%,
82.1%, 78.4%. Our results suggest that the use of HBsAg-positive donors liver
grafts is feasible, since HBV can be controlled without affecting graft
stability. However, the selection of grafts and the postoperative antiviral
therapy should be managed appropriately.
PMID- 28405141
TI - Effect of a poloxamer 407-based thermosensitive gel on minimization of thermal
injury to diaphragm during microwave ablation of the liver.
AB - AIM: To assess the insulating effect of a poloxamer 407 (P407)-based gel during
microwave ablation of liver adjacent to the diaphragm. METHODS: We prepared
serial dilutions of P407, and 22.5% (w/w) concentration was identified as
suitable for ablation procedures. Subsequently, microwave ablations were
performed on the livers of 24 rabbits (gel, saline, control groups, n = 8 in
each). The P407 solution and 0.9% normal saline were injected into the potential
space between the diaphragm and liver in experimental groups. No barriers were
applied to the controls. After microwave ablations, the frequency, size and
degree of thermal injury were compared histologically among the three groups.
Subsequently, another 8 rabbits were injected with the P407 solution and
microwave ablation was performed. The levels of alanine aminotransferase (ALT),
aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr)
in serum were tested at 1 d before microwave ablation and 3 and 7 d after
operation. RESULTS: In vivo ablation thermal injury to the adjacent diaphragm was
evaluated in the control, saline and 22.5% P407 gel groups (P = 0.001-0.040).
However, there was no significant difference in the volume of ablation zone among
the three groups (P > 0.05). Moreover, there were no statistical differences
among the preoperative and postoperative gel groups according to the levels of
ALT, AST, BUN and Cr in serum (all P > 0.05). CONCLUSION: Twenty-two point five
percent P407 gel could be a more effective choice during microwave ablation of
hepatic tumors adjacent to the diaphragm. Further studies for clinical
translation are warranted.
PMID- 28405139
TI - Regulation of intestinal permeability: The role of proteases.
AB - The gastrointestinal barrier is - with approximately 400 m2 - the human body's
largest surface separating the external environment from the internal milieu.
This barrier serves a dual function: permitting the absorption of nutrients,
water and electrolytes on the one hand, while limiting host contact with noxious
luminal antigens on the other hand. To maintain this selective barrier, junction
protein complexes seal the intercellular space between adjacent epithelial cells
and regulate the paracellular transport. Increased intestinal permeability is
associated with and suggested as a player in the pathophysiology of various
gastrointestinal and extra-intestinal diseases such as inflammatory bowel
disease, celiac disease and type 1 diabetes. The gastrointestinal tract is
exposed to high levels of endogenous and exogenous proteases, both in the lumen
and in the mucosa. There is increasing evidence to suggest that a dysregulation
of the protease/antiprotease balance in the gut contributes to epithelial damage
and increased permeability. Excessive proteolysis leads to direct cleavage of
intercellular junction proteins, or to opening of the junction proteins via
activation of protease activated receptors. In addition, proteases regulate the
activity and availability of cytokines and growth factors, which are also known
modulators of intestinal permeability. This review aims at outlining the
mechanisms by which proteases alter the intestinal permeability. More knowledge
on the role of proteases in mucosal homeostasis and gastrointestinal barrier
function will definitely contribute to the identification of new therapeutic
targets for permeability-related diseases.
PMID- 28405142
TI - Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced
airway asthma and beta-lactoglobulin-induced intestinal food allergy mouse
models.
AB - AIM: To determine whether oral administration of Bifidobacterium infantis
CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation
and food allergies in a mouse model. METHODS: Ovalbumin (OVA)-induced allergic
asthma and beta-lactoglobulin-induced food allergy mouse models were used in this
study. Following oral administration of B. infantis CGMCC313-2 during or after
allergen sensitization, histopathologic changes in the lung and intestine were
evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse
model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA
specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar
lavage fluid (BALF) were also assessed. In the food allergy mouse model, the
levels of total IgE and cytokines in serum were measured. RESULTS: Oral
administration of B. infantis CGMCC313-2 during or after allergen sensitization
suppressed allergic inflammation in lung and intestinal tissues, while the
proportion of infiltrating inflammatory cells was significantly decreased in the
BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the
serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1
were also observed in OVA-induced allergic asthma mice. The expression of
interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following
the administration of B. infantis CGMCC313-2, while an effect on serum IL-10
levels was not observed. CONCLUSION: B. infantis CGMCC313-2 inhibits the
secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic
inflammation.
PMID- 28405140
TI - Diet and microbiota in inflammatory bowel disease: The gut in disharmony.
AB - Bacterial colonization of the gut shapes both the local and the systemic immune
response and is implicated in the modulation of immunity in both healthy and
disease states. Recently, quantitative and qualitative changes in the composition
of the gut microbiota have been detected in Crohn's disease and ulcerative
colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism
underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes
have co-existed and co-evolved for a long time in a mutually beneficial symbiotic
association essential for maintaining homeostasis. However, the microbiome is
dynamic, changing with age and in response to environmental modifications. Among
such environmental factors, food and alimentary habits, progressively altered in
modern societies, appear to be critical modulators of the microbiota,
contributing to or co-participating in dysbiosis. In addition, food constituents
such as micronutrients are important regulators of mucosal immunity, with direct
or indirect effects on the gut microbiota. Moreover, food constituents have
recently been shown to modulate epigenetic mechanisms, which can result in
increased risk for the development and progression of IBD. Therefore, it is
likely that a better understanding of the role of different food components in
intestinal homeostasis and the resident microbiota will be essential for
unravelling the complex molecular basis of the epigenetic, genetic and
environment interactions underlying IBD pathogenesis as well as for offering
dietary interventions with minimal side effects.
PMID- 28405144
TI - Miniature magnetically anchored and controlled camera system for trocar-less
laparoscopy.
AB - AIM: To design a miniature magnetically anchored and controlled camera system to
reduce the number of trocars which are required for laparoscopy. METHODS: The
system consists of a miniature magnetically anchored camera with a 30 degrees
downward angle, an external magnetically anchored unit, and a vision output
device. The camera weighs 12 g, measures Phi10.5 mm * 55 mm and has two magnets,
a vision model, a light source, and a metal hexagonal nut. To test the prototype,
the camera was inserted through a 12-mm conventional trocar in an ex vivo real
liver laparoscopic training system. A trocar-less laparoscopic cholecystectomy
was performed 6 times using a 12-mm and a 5-mm conventional trocar. In addition,
the same procedure was performed in four canine models. RESULTS: Both procedures
were successfully performed using only two conventional laparoscopic trocars. The
cholecystectomy was completed without any major complication in 42 min (38-45
min) in vitro and in 50 min (45-53 min) using an animal model. This camera was
anchored and controlled by an external unit magnetically anchored on the
abdominal wall. The camera could generate excellent image. with no instrument
collisions. CONCLUSION: The camera system we designed provides excellent optics
and can be easily maneuvered. The number of conventional trocars is reduced
without adding technical difficulties.
PMID- 28405143
TI - Diagnostic value evaluation of trefoil factors family 3 for the early detection
of colorectal cancer.
AB - AIM: The purpose of this study was to evaluate the diagnostic value of trefoil
factor family 3 (TFF3) for the early detection of colorectal cancer (CC).
METHODS: Serum TFF3 and carcino-embryonic antigen (CEA) were detected in 527
individuals, including 115 healthy control (HC), 198 colorectal adenoma (CA), and
214 CC individuals in the training group. RESULTS: Serum TFF3 showed no
significant correlation with age, gender, or tumor location but showed
significant correlation with the tumor stage. Serum TFF3 in the CC group was
significantly higher than in the HC or CA group. The AUC values of TFF3 for
discriminating between HC and CC and between CA and CC were 0.930 (0.903, 0.958)
and 0.834 (0.796, 0.873). A multivariate model combining TFF3 and CEA was built.
Compared to TFF3 or CEA alone, the multivariate model showed significant
improvement (P < 0.001). For discriminating between HC and CC, HC and early stage
CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and
advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%,
93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%,
93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the
sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the
specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%,
respectively. CONCLUSION: The multivariate diagnostic model that included TFF3
and CEA showed significant improvement over the conventional biomarker CEA and
might provide a potential method for the early detection of CC.
PMID- 28405145
TI - Acanthopanax senticosus polysaccharides-induced intestinal tight junction injury
alleviation via inhibition of NF-kappaB/MLCK pathway in a mouse endotoxemia
model.
AB - AIM: To examine the effects of Acanthopanax senticosus polysaccharides (ASPS) on
intestinal tight junction (TJ) disruption and nuclear factor-kappa B (NF
kappaB)/myosin light chain kinase (MLCK) activation in endotoxemia. METHODS:
BALB/C mice (6-8-weeks-old) received continuous intragastric gavage of ASPS for 7
d before injection of lipopolysaccharide (LPS), or received ASPS once after LPS
injection. Blood and intestinal mucosal samples were collected 6 h after LPS
challenge. Clinical symptoms, histological injury, intestinal permeability, TJ
ultrastructure, and TJ protein expression were determined. RESULTS: Compared with
mice in the LPS group, pretreatment with ASPS improved clinical and histological
scores by 390.9% (P < 0.05) and 57.89% (P < 0.05), respectively, and gut
permeability change in endotoxemic mice was shown by a 61.93% reduction in
reduced leakage of fluorescein isothiocyanate-dextran 6 h after LPS injection (P
< 0.05). ASPS pretreatment also prevented LPS-induced TJ ultrastructure breakdown
supported by increased electron dense materials between adjoining cells,
sustained redistribution and expression of occludin (0.597 +/- 0.027 vs 0.103 +/-
0.009, P < 0.05) and zonula occludens-1 (0.507 +/- 0.032 vs 0.125 +/- 0.019, P <
0.05), and suppressed activation of the NF-kappaB/MLCK pathway indicated by
reduced expression of NF-kappaB, phospho-inhibitor kappa B-alpha, MLCK and
phospho-myosin light-chain-2 by 16.06% (P < 0.05), 54.31% (P < 0.05), 66.10% (P <
0.05) and 64.82% (P < 0.05), respectively. CONCLUSION: ASPS pretreatment may be
associated with inhibition of the NF-kappaB/MLCK pathway and concomitant
amelioration of LPS-induced TJ dysfunction of intestinal epithelium in
endotoxemia.
PMID- 28405146
TI - Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in
patients resected for focal pancreatic mass.
AB - AIM: To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic
resections performed for focal pancreatic enlargement. METHODS: We performed a
retrospective analysis of medical records of all patients who underwent
pancreatic resection for a focal pancreatic enlargement at our tertiary center
from January 2000 to July 2013. The indication for surgery was suspicion of a
tumor based on clinical presentation, imaging findings and laboratory
evaluations. The diagnosis of AIP was based on histology findings. An experienced
pathologist specialized in pancreatic disease reviewed all the cases and
confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The
histological diagnosis of AIP was set according to the international consensus
diagnostic criteria. RESULTS: Two hundred ninety-five pancreatic resections were
performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men
and 3 women) based on histology of the resected specimen. Six of them had AIP
type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was
also present in six patients with AIP (40%), all six were men. Patients with AIP
+ PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely
to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had
experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients
without PC. AIP was not diagnosed in any patients prior to surgery; however, the
diagnostic algorithm was not fully completed in every case. CONCLUSION: The
possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP
does not rule out simultaneous presence of PC.
PMID- 28405147
TI - Endosonographic surveillance of 1-3 cm gastric submucosal tumors originating from
muscularis propria.
AB - AIM: To observe the natural course of 1-3 cm gastric submucosal tumors
originating from the muscularis propria (SMTMPs). METHODS: By reviewing the
computerized medical records over a period of 14 years (2000-2013), patients with
1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound (EUS)
examinations were enrolled. Tumor progression was defined as a >= 1.2 times
enlargement in tumor diameter observed during EUS surveillance. All patients were
divided into stationary and progressive subgroups and further analyzed. We also
reviewed the patients in the progressive subgroup again in 2016. RESULTS: A total
of 88 patients were studied, including 25 in the progressive subgroup. The mean
time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in
the progressive subgroup. Risk factors for tumor progression included larger
tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a
cut-off size for predicting tumor progression. Seventeen patients underwent
surgery, of whom 13 had gastrointestinal stromal tumors (GISTs) and 4 had
leiomyomas. Tumor progression was found only in patients with GISTs. All of the
tumors exhibited benign behaviors without metastasis until 2016. CONCLUSION: Most
1-3 cm gastric SMTMPs (71.6%) are indolent. Tumor progression was found only in
GISTs, and it is a good predictor for differentiating GISTs from leiomyomas.
Predictors of tumor progression include larger tumor size (> 14.0 mm) and
irregular border.
PMID- 28405148
TI - Effect of liver cirrhosis on long-term outcomes after acute respiratory failure:
A population-based study.
AB - AIM: To assessed the effect of liver cirrhosis (LC) on the poorly understood long
term mortality risk after first-ever mechanical ventilation (1-MV) for acute
respiratory failure. METHODS: All patients in Taiwan given a 1-MV between 1997
and 2013 were identified in Taiwan's Longitudinal Health Insurance Database 2000.
Each patient with LC was individually matched, using a propensity-score method,
to two patients without LC. The primary outcome was death after a 1-MV. RESULTS:
A total of 16653 patients were enrolled: 5551 LC-positive (LC[Pos]) patients,
including 1732 with cryptogenic LCs and 11102 LC-negative (LC[Neg]) controls.
LC[Pos] patients had more organ failures and were more likely to be admitted to
medical department than were LC[Neg] controls. LC[Pos] patients had a
significantly lower survival rate (AHR = 1.38, 95%CI: 1.32-1.44). Moreover, the
mortality risk was significantly higher for patients with non-cryptogenic LC than
for patients with cryptogenic LC (AHR = 1.43, 95%CI: 1.32-1.54) and patients
without LC (AHR = 1.56, 95%CI: 1.32-1.54). However, there was no significant
difference between patients with cryptogenic and without LC (HR = 1.05, 95%CI:
0.98-1.12). CONCLUSION: LC, especially non-cryptogenic LC, significantly
increases the risk of death after a 1-MV.
PMID- 28405149
TI - possible role of soluble fibrin monomer complex after gastroenterological
surgery.
AB - AIM: To examine the role of soluble fibrin monomer complex (SFMC) in the
prediction of hypercoagulable state after gastroenterological surgery. METHODS:
We collected data on the clinical risk factors and fibrin-related makers from
patients who underwent gastroenterological surgery at Hiroshima University
Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical
significance of SFMC, which is known to reflect the early plasmatic activation of
coagulation, in the view of these fibrin related markers. RESULTS: A total of 123
patients were included in the present study. There were no patients with
symptomatic VTE. Thirty-five (28%) patients received postoperative anticoagulant
therapy. In the multivariate analysis, a high SFMC level on POD 1 was
independently associated with D-dimer elevation on POD 7 (OR = 4.31, 95%CI: 1.10
18.30, P = 0.03). The cutoff SFMC level was 3.8 MUg/mL (AUC = 0.78, sensitivity,
63%, specificity, 89%). The D-dimer level on POD 7 was significantly reduced in
high-SFMC patients who received anticoagulant therapy in comparison to high-SFMC
patients who did not. CONCLUSION: The SFMC on POD 1 strongly predicted the
hypercoagulable state after gastroenterological surgery than the clinical risk
factors and the other fibrin related markers.
PMID- 28405150
TI - Comparing acid steatocrit and faecal elastase estimations for use in M-ANNHEIM
staging for pancreatitis.
AB - AIM: To compare two tests for exocrine pancreatic function (EPF) for use in M
ANNHEIM staging for pancreatitis. METHODS: One hundred and ninety four
consecutive patients with acute pancreatitis (AP; n = 13), recurrent acute
pancreatitis (RAP; n = 65) and chronic pancreatitis (CP; n = 116) were enrolled.
EPF was assessed by faecal elastase-1 (FE-1) estimation and stool fat excretion
by the acid steatocrit method. Patients were classified as per M-ANNHEIM stages
separately based on the results of the two tests for comparison. Independent
Student's t-test, chi2 test, Kruskal-Wallis test, Mann-Whitney U test and
McNemar's test were used as appropriate. RESULTS: Sixty-one (52.5%) patients with
CP had steatorrhoea when assessed by the acid steatocrit method; 79 (68.1%) with
CP had exocrine insufficiency by the FE-1 test (chi2 test, P < 0.001). The
results of acid steatocrit and FE-1 showed a significant negative correlation
(Spearman's rho = -0.376, P < 0.001). A statistically significant difference was
seen between the M-ANNHEIM stages as classified separately by acid steatocrit and
the FE-1. Thirteen (6.7%), 87 (44.8%), 89 (45.8%) and 5 (2.5%) patients were
placed in M-ANNHEIM stages 0, I, II, and III respectively, with the use of acid
steatocrit as against 13 (6.7%), 85 (43.8%), 75 (38.6%), and 21 (10.8%)
respectively by FE-1 in stages 0, I, II, and III thereby altering the stage in 28
(14.4%) patients (P < 0.001, McNemar's test). CONCLUSION: FE-1 estimation
performed better than the acid steatocrit test for use in the staging of
pancreatitis by the M-ANNHEIM classification since it diagnosed a higher
proportion of patients with exocrine insufficiency.
PMID- 28405151
TI - Systematic review: The placebo effect of psychological interventions in the
treatment of irritable bowel syndrome.
AB - AIM: To determine the placebo response rate associated with different types of
placebo interventions used in psychological intervention studies for irritable
bowel syndrome. METHODS: Randomized controlled trials comparing psychological
interventions (stress management/relaxation therapy (cognitive) behavioral
therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of
adult patients with irritable bowel syndrome (IBS) diagnosed with the Manning or
Rome criteria with an adequate placebo control treatment and reporting data on
IBS symptom severity were identified by searching PubMed, Embase, the Cochrane
Library, CINAHL and PsycINFO databases. Full-text articles that were written in
English and published between 1966 and February 2016 in peer-reviewed journals
were selected for the present review. Placebo interventions were considered to be
adequate if the number of sessions and the amount of time spent with the
therapist were the same as in the active treatment. The placebo response rate
(PRR) was computed for IBS symptom severity (primary outcome measure) as well as
for anxiety, depression and quality of life (secondary outcome measures).
RESULTS: Six studies, with a total of 555 patients met the inclusion criteria.
Four studies used an educational intervention, whereas two studies used a form of
supportive therapy as the placebo intervention. The PRR for IBS symptom severity
ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the
secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for
depression 20% to 125% for quality of life. The PRR associated with
pharmacological treatments, treatment with dietary bran and complementary
medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in
studies on psychological interventions was comparable to that in studies on
pharmacological, dietary and alternative medical interventions. CONCLUSION: The
PRR is probably determined to a larger extent by patient-related factors, such as
expectations and desire for the treatment to be effective, than the content of
the placebo intervention.
PMID- 28405152
TI - Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk:
A meta-analysis.
AB - AIM: To perform a meta-analysis to investigate the association between
cyclooxygenase-2 (COX-2) -1195G>A gene polymorphism and gastrointestinal cancers.
METHODS: Publications related to the COX-2 -1195G>A gene polymorphism and
gastrointestinal cancers published before July 2016 were retrieved from PubMed,
EMBASE, Web of Science, China Biological Medicine Database, China National
Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using
Stata11.0 software. The strength of the association was evaluated by calculating
the combined odds ratios (ORs) and the corresponding 95%CIs. The retrieved
publications were excluded or included one by one for sensitivity analysis. In
addition, the funnel plot, Begg's rank correlation test, and Egger's linear
regression method were applied to analyse whether the included publications had
publication bias. RESULTS: A total of 24 publications related to the COX-2
1195G>A gene polymorphism were included, including 28 studies involving 11043
cases and 18008 controls. The meta-analysis results showed that the COX-2
1195G>A gene polymorphism significantly correlated with an increased risk of
gastrointestinal cancers, particularly gastric cancer (A vs G: OR = 1.35; AA/AG
vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR =
1.35). Compared to the Caucasian population in America and Europe, the COX-2
1195G>A gene polymorphism in the Asian population (A vs G: OR = 1.30; AA/AG vs
GG: OR = 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37)
significantly increased gastrointestinal cancer risk. The sensitivity analysis (P
< 0.05) and the false positive report probability (P < 0.2) confirmed the
reliability of the results. CONCLUSION: The results showed that the COX-2
1195G>A gene polymorphism might be a potential risk factor for gastrointestinal
cancers. Further validation by a large homogeneous study is warranted.
PMID- 28405153
TI - Esophageal squamous papillomas with focal dermal hypoplasia and eosinophilic
esophagitis.
AB - Focal dermal hypoplasia (FDH) is a rare disorder of the mesodermal and ectodermal
tissues. Here we present an eight-year-old female known to have FDH who presents
with poor weight gain and dysphagia. She was diagnosed with multiple esophageal
papillomas and eosinophilic esophagitis. She was successfully treated with argon
plasma coagulation and ingested fluticasone propionate, which has not been
described previously in a child.
PMID- 28405154
TI - Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A
case report.
AB - Breast cancer with stomach metastasis rare with an incidence of 1% or less among
metastatic breast cancer patients. We experienced a case of breast cancer
metastasizing to the stomach in 65-year-old female patient. She experienced
dyspepsia and poor oral intake before visiting the clinic. Diffuse infiltration
with nodular mucosal thickening of the stomach wall was observed, suggesting
advanced gastric cancer based on gross endoscopic finding. Spread of poorly
cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin
stain resembled signet ring cell carcinoma, but diffuse positive staining for
GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast
cancer metastasizing to the stomach. Based on the final diagnosis, systemic
chemotherapy was administered instead of primary surgical resection. After 2
cycles of docetaxel administration, she showed a partial response based on
abdominal computed tomography scan. This case is an unusual presentation of
breast cancer metastasizing to the gastrointestinal tract.
PMID- 28405156
TI - Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?
AB - The manuscript titled "Vacuoles of Candida yeast behave as a specialized niche
for Helicobacter pylori (H. pylori)" not only has not been prepared in a
scientific manner but the methodology used was not adequate, and therefore the
conclusion reached was not correct. First of all, "yeast" is a broad terminology
covering a great number of genera and species of unicellular micro-organisms. The
authors should have defined the organism with its binary scientific name. This
measure would allow experiment reproduction by the scientific community.
Moreover, the criteria established by Robert Koch to identify a specific
microorganism or pathogen was not adopted in the methodology used. Regarding the
methodology applied, use of the chicken egg-yolk (IgY) antibody and PCR of the
apparently tainted yeast population to prove H. pylori existence in the yeast
vacuoles might be main factors for their wrong conclusions. Bacterial tropism
toward yeast extract is a known phenomenon, and yeast extract is one of the main
ingredients in culture media. Their internalization through phagocytosis or
similar pathways does not seem possible or practical because of the thick and
cellulosic yeast wall. While the small size of yeast cells does not support their
ability in harboring several H. pylori, other observations such as inefficiency
of anti-fungal therapy as anti-Helicobacter therapy strongly reject the
conclusion reached by the above-mentioned article.
PMID- 28405155
TI - Multiple clear-cell sarcomas of small intestine with parotid gland metastasis: A
case report.
AB - Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays
melanocytic differentiation with a distinct molecular profile. It is rarely
localized in the gastrointestinal tract. Herein we reported a case of multiple
synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland
metastasis. A 51-year-old male patient presented with a growing painless mass
under the right ear. A preoperative positron emission tomography/computed
tomography showed multiple intestinal masses and a mass in the right parotid with
increased glucose uptake, and he underwent operative treatment with resection of
three tumors in the jejunum and ileum and then received a right parotidectomy.
Postoperative pathological examination showed that cells in the intestinal tumor
were consistent with clear-cell sarcoma of the gastrointestinal tract, and the
malignant cells in the parotid gland were similar to the intestinal tumor.
Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and
S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ
hybridization.
PMID- 28405157
TI - Decitabine reverses TGF-beta1-induced epithelial-mesenchymal transition in non
small-cell lung cancer by regulating miR-200/ZEB axis.
AB - OBJECTIVE: Epithelial-mesenchymal transition (EMT) is a crucial driver of tumor
progression. Tumor growth factor-beta 1 (TGF-beta1) is an important factor in EMT
induction in tumorigenesis. The targeting of EMT may, therefore, represent a
promising approach in anticancer treatment. METHODS: In this study, we determined
the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-beta1-induced
EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed
the involvement of the miR-200/ZEB axis. RESULTS: Decitabine reversed TGF-beta1
induced EMT in PC9 cells, but not in A549 cells. This phenomenon was associated
with epigenetic changes in the miR-200 family, which regulated EMT by altering
the expression of ZEB1 and ZEB2. TGF-beta1 induced aberrant methylation in miR
200 promoters, leading to EMT in PC9 cells. Decitabine attenuated this effect and
inhibited tumor cell migration in vitro and in vivo. In A549 cells, however,
neither TGF-beta1 nor decitabine exhibited an effect on miR-200 promoter
methylation. CONCLUSION: Our findings suggest that epigenetic regulation of the
miR-200/ZEB axis is responsible for EMT induction by TGF-beta1 in PC9 cells.
Decitabine inhibits EMT in NSCLC cell PC9 through its epigenetic-based
therapeutic activity.
PMID- 28405158
TI - Patient experience with intravenous biologic therapies for ankylosing
spondylitis, Crohn's disease, psoriatic arthritis, psoriasis, rheumatoid
arthritis, and ulcerative colitis.
AB - OBJECTIVE: The objective of this study was to describe patient experience with
intravenous (IV) biologics for ankylosing spondylitis, Crohn's disease, psoriatic
arthritis, psoriasis, rheumatoid arthritis, or ulcerative colitis. METHODS: Semi
structured telephone interviews were conducted in 405 patients with these
autoimmune diseases who were receiving an IV biologic to treat their disease.
RESULTS: On a 7-point scale (1= not at all satisfied; 7= very satisfied), mean
satisfaction with IV medication was rated 6.1; 77% of patients rated satisfaction
as 6 or 7. The most frequently perceived benefits of IV therapy were related to
supervision provided by health care professionals. Most patients (82%, n=332)
preferred their IV medication to subcutaneous injection. The three most common
reasons for preferring IV were not wanting to self-inject (43%), less frequent
dosing (34%), and preference for administration by a health care professional
(24%). African-American/black patients had a stronger preference for IV
administration than Caucasian/white patients (97% vs 80%, P<0.05) and a greater
dislike of needles/self-injection (71% vs 40%, P<0.05). Hospital outpatient
departments were not rated as well as physician in-office infusion. Only half
(49%) of the patients reported that both they and their physician equally
influenced the choice to switch from subcutaneous to IV therapy, and only 30%
were given a choice of infusion center. CONCLUSION: Users of IV biologics are
highly satisfied with their medications and perceive the opportunity for health
care provider interaction at their infusion facilities as an advantage of their
regimen. These findings support continued need for IV therapeutic options and
shared decision-making between patients and physicians while selecting biologic
treatments.
PMID- 28405159
TI - Validation of an instrument to measure patients' experiences of medicine use: the
Living with Medicines Questionnaire.
AB - BACKGROUND: Medicine-related burden is an increasingly recognized concept,
stemming from the rising tide of polypharmacy, which may impact on patient
behaviors, including nonadherence. No instruments currently exist which
specifically measure medicine-related burden. The Living with Medicines
Questionnaire (LMQ) was developed for this purpose. OBJECTIVE: This study
validated the LMQ in a sample of adults using regular prescription medicines in
the UK. METHODS: Questionnaires were distributed in community pharmacies and
public places in southeast England or online through UK health websites and
social media. A total of 1,177 were returned: 507 (43.1%) from pharmacy
distribution and 670 (56.9%) online. Construct validity was assessed by principal
components analysis and item reduction undertaken on the original 60-item pool.
Known-groups analysis assessed differences in mean total scores between
participants using different numbers of medicines and between those who did or
did not require assistance with medicine use. Internal consistency was assessed
by Cronbach's alpha. Free-text comments were analyzed thematically to
substantiate underlying dimensions. RESULTS: A 42-item, eight-factor structure
comprising intercorrelated dimensions (patient-doctor relationships and
communication about medicines, patient-pharmacist communication about medicines,
interferences with daily life, practical difficulties, effectiveness, acceptance
of medicine use, autonomy/control over medicines and concerns about medicine use)
was derived, which explained 57.4% of the total variation. Six of the eight
subscales had acceptable internal consistency (alpha>0.7). More positive
experiences were observed among patients using eight or fewer medicines compared
to nine or more, and those independent with managing/using their medicines versus
those requiring assistance. Free-text comments, provided by almost a third of the
respondents, supported the domains identified. CONCLUSION: The resultant LMQ-2 is
a valid and reliable multidimensional measure of prescription medicine use
experiences, which covers more diverse domains than existing questionnaires.
However, further validation work is necessary.
PMID- 28405160
TI - Factors influencing adherence to psychopharmacological medications in psychiatric
patients: a structural equation modeling approach.
AB - PURPOSE: To evaluate pathways through which sociodemographic, clinical,
attitudinal, and perceived health control variables impact psychiatric patients'
adherence to psychopharmacological medications. METHOD: A sample of 966
consecutive psychiatric outpatients was studied. The variables were
sociodemographic (age, gender, and education), clinical (diagnoses, drug
treatment, and treatment duration), attitudinal (attitudes toward
psychopharmacological medication and preferences regarding participation in
decision-making), perception of control over health (health locus of control,
self-efficacy, and psychological reactance), and level of adherence to
psychopharmacological medications. Structural equation modeling was applied to
examine the nonstraightforward relationships and the interactive effects among
the analyzed variables. RESULTS: Structural equation modeling demonstrated that
psychiatric patients' treatment adherence was associated: 1) negatively with
cognitive psychological reactance (adherence decreased as cognitive psychological
reactance increased), 2) positively with patients' trust in their psychiatrists
(doctors' subscale), 3) negatively with patients' belief that they are in control
of their mental health and that their mental health depends on their own actions
(internal subscale), and 4) positively (although weakly) with age. Self-efficacy
indirectly influenced treatment adherence through internal health locus of
control. CONCLUSION: This study provides support for the hypothesis that
perceived health control variables play a relevant role in psychiatric patients'
adherence to psychopharmacological medications. The findings highlight the
importance of considering prospective studies of patients' psychological
reactance and health locus of control as they may be clinically relevant factors
contributing to adherence to psychopharmacological medications.
PMID- 28405161
TI - Mucoactive and antioxidant medicines for COPD: consensus of a group of Chinese
pulmonary physicians.
AB - Airway mucus hypersecretion is a frequent symptom associated with acute and
chronic airway disease. Inhibition of mucus production or promotion of mucolysis
not only relieved symptoms but also improved disease outcomes. There are numerous
available mucoactive medicines for prescription, and how to select them properly
for different diseases is important for clinical practice. So far, there is no
one consensus or guideline reported. A group of Chinese pulmonary physicians
worked together to complete this consensus based on literature review, summarized
mechanism and usage of each classical mucoactive medicine. In general,
antioxidant mucoactive medicines play an important role in chronic airway
disease, including but not limited to airway mucus clearance, reduced acute
exacerbation and improved pulmonary function.
PMID- 28405162
TI - Barriers and enablers of physical activity engagement for patients with COPD in
primary care.
AB - BACKGROUND: Given that physical activity (PA) has a positive impact on COPD
symptoms and prognosis, this study examined the factors that both encourage and
limit participation in PA for individuals with COPD in a primary care setting
from the perspective of social cognitive theory. METHODS: A purposive sample of
26 individuals with a range of COPD severity (age range: 50-89 years; males =15)
were recruited from primary care to participate in one of four focus groups.
Thematic analysis was undertaken to identify key concepts related to their self
efficacy beliefs. RESULTS: Several barriers and enablers closely related to self
efficacy beliefs and symptom severity were identified. The main barriers were
health related (fatigue, mobility problems, breathing issues caused by the
weather), psychological (embarrassment, fear, frustration/disappointment),
attitudinal (feeling in control of their condition, PA perception, older age
perception), and motivational. The main enabling factors were related to
motivation (autonomous or controlled), attitudes, self-regulation, and
performance accomplishments. CLINICAL IMPLICATIONS: When designing interventions
for individuals with COPD, it is important to understand the patient-specific
social cognitive influences on PA participation. This information can then inform
individually tailored management planning.
PMID- 28405163
TI - Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell
penetrating peptide-modified liposomal system.
AB - As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited
to silence critical genes involved in tumor initiation and progression. However,
development of a desirable delivery system is required to overcome the
unfavorable properties of siRNA such as its high degradability, molecular size,
and negative charge to help increase its accumulation in tumor tissues and
promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic
acids. In this study, we developed a new activatable cell-penetrating peptide
(ACPP) that is responsive to an acidic tumor microenvironment, which was then
used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a
cell-penetrating peptide (CPP), an acid-labile linker (hydrazone), and a
polyanionic domain, including glutamic acid and histidine. In the systemic
circulation (pH 7.4), the surface polycationic moieties of the CPP (polyarginine)
are "shielded" by the intramolecular electrostatic interaction of the inhibitory
domain. When exposed to a lower pH, a common property of solid tumors, the ACPP
undergoes acid-catalyzed breakage at the hydrazone site, and the consequent
protonation of histidine residues promotes detachment of the inhibitory peptide.
Subsequently, the unshielded CPP would facilitate the cellular membrane
penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A
series of investigations demonstrated that once exposed to an acidic pH, the ACPP
modified liposomes showed elevated cellular uptake, downregulated expression of
polo-like kinase 1, and augmented cell apoptosis. In addition, favorable siRNA
avoidance of the endosome/lysosome was observed in both MCF-7 and A549 cells,
followed by effective cytoplasmic release. In view of its acid sensitivity and
therapeutic potency, this newly developed pH-responsive and ACPP-mediated
liposome system represents a potential platform for siRNA-based cancer treatment.
PMID- 28405165
TI - Enhancement of physicochemical properties of nanocolloidal carrier loaded with
cyclosporine for topical treatment of psoriasis: in vitro diffusion and in vivo
hydrating action.
AB - Psoriasis is a chronic autoimmune disease that cannot be cured. It can however be
controlled by various forms of treatment, including topical, systemic agents, and
phototherapy. Topical treatment is the first-line treatment and favored by most
physicians, as this form of therapy has more patient compliance. Introducing a
nanoemulsion for transporting cyclosporine as an anti-inflammatory drug to an
itchy site of skin disease would enhance the effectiveness of topical treatment
for psoriasis. The addition of nutmeg and virgin coconut-oil mixture, with their
unique properties, could improve cyclosporine loading and solubility. A high
shear homogenizer was used in formulating a cyclosporine-loaded nanoemulsion. A D
optimal mixture experimental design was used in the optimization of nanoemulsion
compositions, in order to understand the relationships behind the effect of
independent variables (oil, surfactant, xanthan gum, and water content) on
physicochemical response (particle size and polydispersity index) and rheological
response (viscosity and k-value). Investigation of these variables suggests two
optimized formulations with specific oil (15% and 20%), surfactant (15%), xanthan
gum (0.75%), and water content (67.55% and 62.55%), which possessed intended
responses and good stability against separation over 3 months' storage at
different temperatures. Optimized nanoemulsions of pH 4.5 were further studied
with all types of stability analysis: physical stability, coalescence-rate
analysis, Ostwald ripening, and freeze-thaw cycles. In vitro release proved the
efficacy of nanosize emulsions in carrying cyclosporine across rat skin and a
synthetic membrane that best fit the Korsmeyer-Peppas kinetic model. In vivo skin
analysis towards healthy volunteers showed a significant improvement in the
stratum corneum in skin hydration.
PMID- 28405166
TI - EGFR mutation in squamous cell carcinoma of the lung: does it carry the same
connotation as in adenocarcinomas?
AB - BACKGROUND: EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the
outcomes of EGFR mutation-positive adenocarcinomas of the lung. In contrast, the
significance of EGFR mutation in metastatic squamous cell carcinoma (SCC) of the
lung has been debated. METHODS: All patients with metastatic SCC who underwent
EGFR mutation testing at our center from 2010 to 2015 were included for analysis.
EGFR kinase domain mutations were tested using Taqman-based real-time polymerase
chain reaction (PCR). Response assessment was done using Response Evaluation
Criteria In Solid Tumors (RECIST) 1.1. Kaplan-Meier method was used for
calculating progression-free survival (PFS) and overall survival (OS). RESULTS:
EGFR mutation was detected in 29 out of 639 patients with SCC. Furthermore, 19
out of the 29 patients received TKIs at some point during their treatment. TKI
therapy led to a partial response in 5 out of 19 patients and stable disease in 4
out of 19 patients. The median PFS of patients treated with TKIs was 5.0 months.
The median OS of the whole EGFR-positive SCC cohort was 6.6 months. On univariate
analysis, patients having received TKI therapy was the only factor associated
with a significantly better OS of 13.48 months versus 2.58 months (P=0.000). On
multivariate analysis, patients receiving TKI therapy, Eastern Cooperative
Oncology Group-Performance Scale (ECOG-PS) score <2, EGFR exon 19 mutation and
nonsmoking status were associated with significantly better OS. CONCLUSION: EGFR
mutation in SCC of the lung predicts a better outcome if the patient is given
TKI, but it may be inferior to the outcomes seen in EGFR-positive adenocarcinomas
treated with TKI.
PMID- 28405164
TI - A dual-mediated liposomal drug delivery system targeting the brain: rational
construction, integrity evaluation across the blood-brain barrier, and the
transporting mechanism to glioma cells.
AB - As the global population ages, cancer rates increase worldwide, and degenerative
diseases of the central nervous system (CNS), brain tumors, and inflammation
threaten human health more frequently. We designed a dual-mediated (receptor
mediated and adsorption-mediated) liposome, named transferrin-cell penetrating
peptide-sterically stabilized liposome (TF-CPP-SSL), to improve therapy for
gliomas through combining molecular recognition of transferrin receptors (TF-Rs)
on the blood-brain barrier (BBB) and glioma cells with the internalization and
lysosomal escaping ability of CPP. Based on the systematic investigation of
structure-activity relations on the cellular level, we constructed TF-CPP-SSL
rationally by conjugating TF and CPP moieties to the liposomes via PEG3.4K and
PEG2.0K, respectively, and found the optimum densities of TF and CPP were 1.8%
and 4%, respectively. These liposomes had the highest targeting efficacy for
brain microvascular endothelial cell and C6 cell uptake but avoided capture by
normal cells. Fluorescence resonance energy transfer technology and coculture
models of BBB and glioma C6 cells indicated that TF-CPP-SSL was transported
across the BBB without drug leakage, liposome breakup, or cleavage of ligand. TF
CPP-SSL offered advantages for crossing the BBB and entering into glioma C6
cells. Real-time confocal viewing revealed that TF-CPP-SSL was entrapped in
endosomes of glioma C6 cells and then escaped from lysosomes successfully to
release the liposomal contents into the cytosol. Entrapped contents, such as
doxorubicin, could then enter the nucleus to exert pharmacological effects.
PMID- 28405168
TI - The "black evil" affecting patients with diabetes: a case of rhino orbito
cerebral mucormycosis causing Garcin syndrome.
AB - Mucormycosis is a life-threatening infection affecting patients with diabetes. It
is an angioinvasive disease often resistant to treatment with a debilitating
course and high mortality. Here, we report a case of a 45 year old woman with
type 2 diabetes mellitus who presented to us with history of right-sided ptosis
and facial palsy, and subsequently developed loss of vision and palatal palsy.
She was in diabetic ketoacidosis. Nervous system examination revealed involvement
of right second, third, fourth, sixth, seventh, ninth, and tenth cranial nerves,
suggestive of Garcin syndrome. The hard palate had been eroded with formation of
black eschar. Computed tomography of paranasal sinuses revealed right maxillary
and ethmoid sinusitis, with spread of inflammation to infratemporal fossa and
parapharynygeal neck spaces. Debridement of sinus mucosa was done, and culture of
the same yielded growth of rhizopus species. Histopathological examination of the
tissue showed angioinvasion and fungal hyphae suggestive of mucormycosis. She was
treated with amphotericin B, posaconazole, and periodic nasal sinus debridement,
but her general condition worsened after 8 weeks due to secondary sepsis and she
succumbed to death.
PMID- 28405167
TI - Genetic variants and increased risk of meningioma: an updated meta-analysis.
AB - PURPOSE: Various genetic variants have been reported to be linked to an increased
risk of meningioma. However, no confirmed conclusion has been obtained. The
purpose of the study was to investigate potential meningioma-associated gene
polymorphisms, based on published evidence. MATERIALS AND METHODS: An updated
meta-analysis was performed in September 2016. After electronic database
searching and study screening, we selected eligible case-control studies and
extracted data for meta-analysis, using Mantel-Haenszel statistics. P-values,
pooled odds ratios (ORs), and 95% confidence intervals were calculated. RESULTS:
We finally selected eight genes with ten polymorphisms: MLLT10 rs12770228, CASP8
rs1045485, XRCC1 rs1799782, rs25487, MTHFR rs1801133, rs1801131, MTRR rs1801394,
MTR rs1805087, GSTM1 null/present, and GSTT1 null/present. Results of meta
analyses showed that there was increased meningioma risk in case groups under all
models of MLLT10 rs12770228 (all OR >1, P<0.001), compared with control groups.
Similar results were observed under the allele, homozygote, dominant, and
recessive models of MTRR rs1801394 (all OR >1, P<0.05), and the heterozygote and
dominant models of MTHFR rs1801131 in the Caucasian population (all OR >1,
P<0.05). However, no significantly increased meningioma risks were observed for
CASP8 rs1045485, XRCC1 rs25487, rs1799782, MTHFR rs1801133, MTR rs1805087, or
GSTM1/GSTT1 null mutations. CONCLUSION: Our updated meta-analysis provided
statistical evidence for the role of MLLT10 rs12770228, MTRR rs1801394, and MTHFR
rs1801131 in increased susceptibility to meningioma.
PMID- 28405169
TI - Oxidant-induced autophagy and ferritin degradation contribute to epithelial
mesenchymal transition through lysosomal iron.
AB - PURPOSE: Transforming growth factor (TGF)-beta1 triggers epithelial-mesenchymal
transition (EMT) through autophagy, which is partly driven by reactive oxygen
species (ROS). The aim of this study was to determine whether leaking lysosomes
and enhanced degradation of H-ferritin could be involved in EMT and whether it
could be possible to prevent EMT by iron chelation targeting of the lysosome.
MATERIALS AND METHODS: EMT, H-ferritin, and autophagy were evaluated in TGF-beta1
stimulated A549 human lung epithelial cells cultured in vitro using Western
blotting, with the additional morphological assessment of EMT. By using
immunofluorescence and flow cytometry, lysosomes and ROS were assessed by
acridine orange and 6-carboxy-2',7'-dichlorodihydrofluorescein acetate assays,
respectively. RESULTS: TGF-beta1-stimulated cells demonstrated a loss of H
ferritin, which was prevented by the antioxidant N-acetyl-L-cysteine (NAC) and
inhibitors of lysosomal degradation. TGF-beta1 stimulation generated ROS and
autophagosome formation and led to EMT, which was further promoted by the
additional ROS-generating cytokine, tumor necrosis factor-alpha. Lysosomes of TGF
beta1-stimulated cells were sensitized to oxidants but also completely protected
by lysosomal loading with dextran-bound deferoxamine (DFO). Autophagy and EMT
were prevented by NAC, DFO, and inhibitors of autophagy and lysosomal
degradation. CONCLUSION: The findings of this study support the role of enhanced
autophagic degradation of H-ferritin as a mechanism for increasing the
vulnerability of lysosomes to iron-driven oxidant injury that triggers further
autophagy during EMT. This study proposes that lysosomal leakage is a novel
pathway of TGF-beta1-induced EMT that may be prevented by iron-chelating drugs
that target the lysosome.
PMID- 28405171
TI - Estimation of the depth of the thoracic epidural space in children using magnetic
resonance imaging.
AB - BACKGROUND: The estimation of the distance from the skin to the thoracic epidural
space or skin to epidural depth (SED) may increase the success rate and decrease
the incidence of complications during placement of a thoracic epidural catheter.
Magnetic resonance imaging (MRI) is the most comprehensive imaging modality of
the spine, allowing for the accurate determination of tissue spaces and
distances. The present study uses MRI-derived measurements to measure the SED and
define the ratio between the straight and inclined SEDs at two thoracic levels
(T6-7 and T9-10) in children. METHODS: The T2-weighed sagittal MRI images of 109
children, ranging in age from 1 month to 8 years, undergoing radiological
evaluation unrelated to spine pathology were assessed. The SEDs (inclined and
straight) were determined, and a comparison between the SEDs at two thoracic
levels (T6-7 and T9-10) was made. Univariate and multivariate linear regression
models were used to assess the relationship of the inclined thoracic T6-7 and T9
10 SED measurements with age, height, and weight. RESULTS: Body weight
demonstrated a stronger association with the SED than did the age or height with
R2 values of 0.6 for T6-7 and 0.5 for T9-10. The formulae describing the
relationship between the weight and the inclined SED were T6-7 inclined (mm) = 7
+ 0.9 * kg and T9-10 inclined (mm) = 7 + 0.8 * kg. CONCLUSION: The depth of the
pediatric thoracic epidural space shows a stronger correlation with weight than
with age or height. Based on the MRI data, the predictive weight-based formulas
can serve as guide to clinicians for placement of thoracic epidural catheters.
PMID- 28405170
TI - Hepatitis C virus pharmacogenomics in Latin American populations: implications in
the era of direct-acting antivirals.
AB - In recent years, great progress has been made in the field of new therapeutic
options for hepatitis C virus (HCV) infection. The new direct-acting antiviral
agents (DAAs) represent a great hope for millions of chronically infected
individuals because their use may lead to excellent cure rates with fewer side
effects. In Latin America, the high prevalence of HCV genotype 1 infection and
the significant association of Native American ancestry with risk predictive
single-nucleotide polymorphisms (SNPs) in IFNL4 and ITPA genes highlight the need
to implement new treatment regimens in these populations. However, the universal
accessibility to DAAs is still not a reality in the region as their high cost is
one of the major, although not the only, limiting factors for their broad
implementation. Therefore, under these circumstances, could the assessment of
host genetic markers be a useful tool to prioritize DAA treatment until global
access to these new drugs can be achieved? This review will summarize the
scientific evidences and the potential implications of HCV pharmacogenomics in
this rapidly evolving era of anti-HCV drug development.
PMID- 28405172
TI - Mitogen-activated protein kinase phosphatase-3 (MKP-3) in the surgical wound is
necessary for the resolution of postoperative pain in mice.
AB - Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) and its substrates
(extracellular signal-regulated kinase [ERK] and p38) play an important role in
pathophysiological mechanisms of acute postoperative and chronic neuropathic pain
in the spinal cord. This study aimed to understand the role of MKP-3 and its
target MAPKs at the site of surgical incision in nociceptive behavior. Wild-type
(WT) and MKP-3 knockout (KO) mice underwent unilateral plantar hind paw incision.
Mechanical allodynia was assessed by using von Frey filaments. Peripheral ERK-1/2
and p38 phosphorylation were measured by Western blot. Cell infiltration was
determined using hematoxylin and eosin histological staining. Peripheral
phosphorylated ERK-1/2 (p-ERK-1/2) inhibition was performed in MKP-3 KO mice. In
WT mice, mechanical hypersensitivity was observed on postoperative day 1 (0.69+/
0.17 g baseline vs 0.13+/-0.08 g day 1), which resolved normally by postoperative
day 12 (0.46+/-0.08 g, N=6). In MKP-3 KO mice, this hypersensitivity persisted at
least 12 days after surgery (0.19+/-0.06 g; N=6). KO mice displayed higher
numbers of infiltrating cells (51.4+/-6 cells/0.1 mm2) than WT mice (8.7+/-1.2
cells/0.1 mm2) on postoperative day 1 (vs 5-6 cells/0.1 mm2 at baseline) that
returned to baseline 12 days after surgery (10-12 cells/0.1 mm2). In WT mice,
peripheral p-p38 and p-ERK-1/2 expression increased (5- and 3-fold, respectively)
on postoperative days 1 and 5, and returned to basal levels 7-12 days after
surgery (N=3 per group). Peripheral p-p38 levels in MKP-3 KO mice followed a
similar expression pattern as WT mice. Peripheral p-ERK-1/2 levels in MKP-3 KO
mice remained elevated 12 days after surgery (2.5-fold, N=3 per group).
Administration of PD98059 (MEK inhibitor, N=8, vehicle N=9) reduced p-ERK-1/2
expression in the incised tissue and blocked hypersensitivity in MKP-3 KO mice
(N=6). The findings of this study suggest that MKP-3 is pivotal for normal
resolution of acute postoperative allodynia, through the regulation of peripheral
p-ERK-1/2.
PMID- 28405173
TI - Confounding in observational studies based on large health care databases:
problems and potential solutions - a primer for the clinician.
AB - Population-based health care databases are a valuable tool for observational
studies as they reflect daily medical practice for large and representative
populations. A constant challenge in observational designs is, however, to rule
out confounding, and the value of these databases for a given study question
accordingly depends on completeness and validity of the information on
confounding factors. In this article, we describe the types of potential
confounding factors typically lacking in large health care databases and suggest
strategies for confounding control when data on important confounders are
unavailable. Using Danish health care databases as examples, we present the use
of proxy measures for important confounders and the use of external adjustment.
We also briefly discuss the potential value of active comparators, high
dimensional propensity scores, self-controlled designs, pseudorandomization, and
the use of positive or negative controls.
PMID- 28405174
TI - Predicting the occurrence of headache and back pain in young adults by
biopsychological characteristics assessed at childhood or adolescence.
AB - The aim of the current study was to identify predictors of recurrent headache and
back pain in young adults (aged 18-27 years) from data assessed in childhood or
adolescence, i.e., 9 years before the final survey. Our interest was whether
psychological characteristics contribute to the risk of pain prevalence in adult
age when controlling for already empirically supported risk factors such as
parental pain, pediatric pain and sex. The study was part of a five-wave
epidemiological investigation of >5000 families with children aged between 7 and
14 years when addressed first. In a multiple hierarchical regression analysis,
the abovementioned three variables (Block-I variables) were entered first
followed by five psychological trait variables (Block-II variables:
internalizing, anxiety sensitivity, somatosensory amplification, catastrophizing
and dysfunctional stress coping) to find out the extent of model improvement. The
multivariable hierarchical regression analysis confirmed the hypothesis that the
Block-I variables significantly enhance the risk of future pain at young adult
age. None of the psychological variables did so. Thus, the hypothesis of a
significant surplus predictive effect was not confirmed. The amount of total
explained variance differed strongly between headache and back pain. In
particular, a valid prediction of back pain was not possible. When analyzed
separately in simple regression analysis, psychological variables turned out to
be significant predictors, however, of very low effect size. The inclusion of
Block-I variables in the model clearly reduced the impact of the psychological
variables. This risk profile is discussed in the context of the different
trajectories of headache and back pain from childhood to adult age, which were
proposed by various studies. We propose that a biopsychological characteristic
denoted as emotional negativity, especially regarding self-reference, might be a
common factor behind all selected variables. Risk research in recurrent pain is a
field where much more multidisciplinary research is needed before progress can be
expected.
PMID- 28405175
TI - When and Why Parents Prompt Their Children to Apologize: The Roles of
Transgression Type and Parenting Style.
AB - Young children are sensitive to the importance of apologies, yet little is known
about when and why parents prompt apologies from children. We examined these
issues with parents of 3-10-year-old children (N = 483). Parents judged it to be
important for children to apologize following both intentional and accidental
morally-relevant transgressions, and they anticipated prompting apologies in both
contexts, showing an 'outcome bias' (i.e., a concern for the outcomes of
children's transgressions rather than for their underlying intentions). Parents
viewed apologies as less important after children's breaches of social
convention; parents recognized differences between social domains in their
responses to children's transgressions. Irrespective of parenting style, parents
were influenced in similar fashion by particular combinations of transgressions
and victims, though permissive parents were least likely to anticipate prompting
apologies. Parents endorsed different reasons for prompting apologies as a
function of transgression type, suggesting that they attend to key features of
their children's transgressions when deciding when to prompt apologies.
PMID- 28405176
TI - Discrimination, internalized racism, and depression: A comparative study of
African American and Afro-Caribbean adults in the US.
AB - Emerging research suggests that both perceptions of discrimination and
internalized racism (i.e., endorsement of negative stereotypes of one's racial
group) are associated with poor mental health. Yet, no studies to date have
examined their effects on mental health with racial/ethnic minorities in the US
in a single study. The present study examined: (a) the direct effects of everyday
discrimination and internalized racism on risk of DSM-IV criteria of past-year
major depressive disorder (MDD); (b) the interactive effects of everyday
discrimination and internalized racism on risk of past-year MDD; and (c) the
indirect effect of everyday discrimination on risk of past-year MDD via
internalized racism. Further, we examined whether these associations differed by
ethnic group membership. We utilized nationally representative data of Afro
Caribbean (N = 1,418) and African American (N = 3,570) adults from the National
Survey of American Life. Results revealed that experiencing discrimination was
associated with increased odds of past-year MDD among the total sample. Moreover,
for Afro-Caribbeans, but not African Americans, internalized racism was
associated with decreased odds of meeting criteria for past-year MDD. We did not
find an interaction effect for everyday discrimination by internalized racism,
nor an indirect effect of discrimination on risk of past-year MDD through
internalized racism. Collectively, our findings suggest a need to investigate
other potential mechanisms by which discrimination impacts mental health, and
examine further the underlying factors of internalized racism as a potential self
protective strategy. Lastly, our findings point to the need for research that
draws attention to the heterogeneity within the U.S. Black population.
PMID- 28405177
TI - Mapping mitochondrial heteroplasmy in a Leydig tumor by laser capture micro
dissection and cycling temperature capillary electrophoresis.
AB - BACKGROUND: The growth of tumor cells is accompanied by mutations in nuclear and
mitochondrial genomes creating marked genetic heterogeneity. Tumors also contain
non-tumor cells of various origins. An observed somatic mitochondrial mutation
would have occurred in a founding cell and spread through cell division. Micro
anatomical dissection of a tumor coupled with assays for mitochondrial point
mutations permits new insights into this growth process. More generally, the
ability to detect and trace, at a histological level, somatic mitochondrial
mutations in human tissues and tumors, makes these mutations into markers for
lineage tracing. METHOD: A tumor was first sampled by a large punch biopsy and
scanned for any significant degree of heteroplasmy in a set of sequences
containing known mutational hotspots of the mitochondrial genome. A heteroplasmic
tumor was sliced at a 12 MUm thickness and placed on membranes. Laser capture
micro-dissection was used to take 25000 MUm2 subsamples or spots. After DNA
amplification, cycling temperature capillary electrophoresis (CTCE) was used on
the laser captured samples to quantify mitochondrial mutant fractions. RESULTS:
Of six testicular tumors studied, one, a Leydig tumor, was discovered to carry a
detectable degree of heteroplasmy for two separate point mutations: a C -> T
mutation at bp 64 and a T -> C mutation found at bp 152. From this tumor, 381
spots were sampled with laser capture micro-dissection. The ordered distribution
of spots exhibited a wide range of fractions of the mutant sequences from 0 to
100% mutant copies. The two mutations co-distributed in the growing tumor
indicating they were present on the same genome copies in the founding cell.
CONCLUSION: Laser capture microdissection of sliced tumor samples coupled with
CTCE-based point mutation assays provides an effective and practical means to
obtain maps of mitochondrial mutational heteroplasmy within human tumors.
PMID- 28405178
TI - Utilizing BD MAXTM Enteric Bacterial Panel to Detect Stool Pathogens from Rectal
Swabs.
AB - BACKGROUND: The BD MAXTM Enteric Bacterial Panel (BDM-EBP) is designed and FDA
cleared to detect Salmonella, Shigella, Campylobacter, and Shiga toxin genes
stx1/2 from stool samples. However, rectal swabs, which are not FDA-cleared for
clinical testing with the BDM-EBP, are common specimens received from pediatric
patients for enteric pathogen testing. The purpose of this study was to evaluate
the ability of the BDM-EBP to detect stool pathogens from rectal swabs. METHODS:
Routine cultures, Shiga toxin testing, and molecular testing with BDM-EBP were
performed on 272 sequential rectal swabs collected from August 2015 to December
2015. Discrepant test results were resolved using Verigene(r) Enteric Pathogens
Nucleic Acid Test (EP). 36 challenge samples (13 Salmonella spp., 3 Shigella
spp., 10 Campylobacter spp., and 10 Shiga toxin positive Escherichia coli) were
tested using reference strains (American Type Culture Collection) and previous
patient isolates diluted to103-104 cfu/ml in saline then added to Sample Buffer
Tube (SBT) with negative stool matrix delivered via a swab. Limit of detection
testing was performed by serial 10 fold dilutions in saline then added to SBT
with negative stool matrix provided via a swab. RESULTS: A total of 272 rectal
swab specimens were evaluated and 89 were positive by culture and/or MAX EBP. All
discrepant results were BDM-EBP positive and culture negative. 21 of 31 (68%) of
the apparent false positive BDM-EBP discrepant results resolved as positive with
Nanosphere's Verigene(r) EP. After resolution of the discordant results, the
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are as
follows for each target: Salmonella (n = 4) 100%, PPA and 100%, NPA; Shigella (n
= 79) 100%, PPA and 95.3%, NPA; Campylobacter (n = 4) 100%, PPA and 99.6%, NPA;
and Shiga toxin producing organisms (n = 2) 100%, PPA and 100%, NPA. 8.8% of the
patient samples did not initially yield a result on the BDM-System. Upon repeat,
half of the problematic samples resolved, and 4.4% of the total specimen tested
did not yield a result. All organisms in the challenge samples were detected.
Limits of detection for BDM-EBP testing of rectal swabs were as follows (in
cfu/ml in SBT): Salmonella-1.44 * 102; Shigella-5.10 * 100; Campylobacter-1.51 *
101; and Shiga Toxin-1.13 *103. CONCLUSION: Rectal swabs are acceptable samples
for detecting Salmonella, Shigella, Campylobacter, and Shiga toxin using BDM-EBP.
PMID- 28405180
TI - Intraperitoneal Injection Is Not a Suitable Administration Route for Single
Walled Carbon Nanotubes in Biomedical Applications.
AB - Given the extensive application of carbon nanotubes (CNTs) in biomedical fields,
there is increasing concern regarding unintentional health impacts. Research into
safe usage is therefore increasingly necessary. This study investigated the
responses of the mouse brain to single-walled CNTs (SWCNTs) delivered via
intraperitoneal (IP) injection and compared these results with the previous study
where SWCNTs were delivered via intravenous (IV) injection so as to explore which
administration route is potentially better for SWCNTs application. This study
suggests SWCNTs delivered via IP injection can have negative effects on the mouse
brain through oxidative stress and inflammation at high concentration exposure,
but these responses were not consistent and showed no dose-dependent effect. In a
previous study, the results showed that IV-delivered SWCNTs induced a more
consistent and dose-dependent effect. The comparison of the 2 studies suggested
that using SWCNTs at a safe dosage delivered via IV injection may be a better
administration route for SWCNTs in biomedical applications.
PMID- 28405179
TI - A review of studies of the proteomes of circulating microparticles: key roles for
galectin-3-binding protein-expressing microparticles in vascular diseases and
systemic lupus erythematosus.
AB - Subcellular microvesicles (MVs) have attracted increasing interest during the
past decades. While initially considered as inert cellular debris, several
important roles for MVs in physiological homeostasis, cancer, cardiovascular, and
autoimmune diseases have been uncovered. Although still poorly understood, MVs
are involved in trafficking of information from cell-to-cell, and are implicated
in the regulation of immunity, thrombosis, and coagulation. Different subtypes of
extracellular MVs exist. This review focuses on the cell membrane-derived shedded
MVs (ranging in size from 200 to 1000 nm) typically termed microparticles (MPs).
The numbers and particularly the composition of MPs appear to reflect the state
of their parental cells and MPs may therefore carry great potential as clinical
biomarkers which can be elucidated and developed by proteomics in particular.
Determination of the identity of the specific proteins and their quantities, i.e.
the proteome, in complex samples such as MPs enables an in-depth characterization
of the phenotypical changes of the MPs during disease states. At present, only a
limited number of proteomic studies of circulating MPs have been carried out in
healthy individuals and disease populations. Interestingly, these studies
indicate that a small set of MP-proteins, in particular, overexpression of
galectin-3-binding protein (G3BP) distinguish MPs in patients with venous
thromboembolism and the systemic autoimmune disease, systemic lupus erythematosus
(SLE). G3BP is important in cell-cell adhesion, clearance, and intercellular
signaling. MPs overexpressing G3BP may thus be involved in thrombosis and
hemostasis, vascular inflammation, and autoimmunity, further favoring G3BP as a
marker of "pathogenic" MPs. MPs expressing G3BP may also hold a potential as
biomarkers in other conditions such as cancer and chronic viral infections. This
review highlights the methodology and results of the proteome studies behind
these discoveries and places them in a pathophysiological and biomarker
perspective.
PMID- 28405181
TI - Depression, anxiety and panic disorders in chronic obstructive pulmonary disease
patients: correlations with tobacco use, disease severity and quality of life.
AB - BACKGROUND: The objective of this study is to assess anxiety, depression and
panic disorders among patients diagnosed with COPD and to investigate their
correlation with disease severity, quality of life as well as tobacco use.
METHODS: An observational study was performed between January and September 2014
among 60 patients diagnosed with COPD. COPD staging according to GOLD criteria,
while anxiety and depression were assessed using Hospital Anxiety and Depression
Scale and panic attacks were evaluated based on ICD 10 criteria. RESULTS: Almost
40% of the sample were smokers, the medium packs-years was 34.3 and the medium
Fagerstrom score was 7.5. Overall, mean Modified Medical Research Council Dyspnea
Scale (mMRC) was 2.86, mean COPD Assessment Test (CAT) score was 21.75 and study
participants had 1.93 COPD exacerbations/year. Mean distribution of anxiety and
depression symptoms scores among COPD subjects was 10.65 +/- 3.5 and 9.93 +/-
3.8, respectively. Smokers and ex-smokers had similar scores with regard to
anxiety, depression or the presence of panic attacks. The results of the
bivariate correlations indicated associations between anxiety, depression, panic
attacks and disease severity, as well as poor quality of life of patients with
COPD, regardless of their current tobacco use status. CONCLUSIONS: In conclusion,
the results of this study indicate that anxiety, depression and panic attacks
were constant characteristics among COPD patients- regardless of their current
tobacco use.
PMID- 28405182
TI - A Standardized Protocol for Stereotaxic Intrahippocampal Administration of Kainic
Acid Combined with Electroencephalographic Seizure Monitoring in Mice.
AB - Lack of scientific reproducibility is a growing concern and weak experimental
practices may contribute to irreproducibility. Here, we describe an optimized and
versatile protocol for stereotaxic intrahippocampal administration of Kainic Acid
(KA) in mice with a C57Bl6 background. In this protocol, KA administration is
combined with in vivo recording of neuronal activity with wired and wireless
setups. Following our protocol, KA administration results in a robust dose
dependent induction of low-level epileptiform activity or Status Epilepticus (SE)
and induces previously characterized hallmarks of seizure-associated pathology.
The procedure consists of three main steps: Craniotomy, stereotaxic
administration of KA, and placement of recording electrodes in intrahippocampal,
and subdural locations. This protocol offers extended possibilities compared to
the systemic administration of KA, as it allows the researcher to accurately
regulate the local dose of KA and resulting seizure activity, and permits the use
and study of convulsive and non-convulsive KA doses, resulting in higher
reproducibility and lower inter-individual variability and mortality rates.
Caution should be taken when translating this procedure to different strains of
mice as inter-strain sensitivity to KA has been described before. The procedure
can be performed in ~1 h by a trained researcher, while intrahippocampal
administration of KA without placing recording electrodes can be done in 25 min,
and can be easily adapted to the titrated intrahippocampal administration of
other drugs.
PMID- 28405183
TI - Abnormal Size-Dependent Modulation of Motion Perception in Children with Autism
Spectrum Disorder (ASD).
AB - Excitation/Inhibition (E/I) imbalance in neural networks is now considered among
the core neural underpinnings of autism psychopathology. In motion perception at
least two phenomena critically depend on E/I balance in visual cortex: spatial
suppression (SS), and spatial facilitation (SF) corresponding to impoverished or
improved motion perception with increasing stimuli size, respectively. While SS
is dominant at high contrast, SF is evident for low contrast stimuli, due to the
prevalence of inhibitory contextual modulations in the former, and excitatory
ones in the latter case. Only one previous study (Foss-Feig et al., 2013)
investigated SS and SF in Autism Spectrum Disorder (ASD). Our study aimed to
replicate previous findings, and to explore the putative contribution of
deficient inhibitory influences into an enhanced SF index in ASD-a cornerstone
for interpretation proposed by Foss-Feig et al. (2013). The SS and SF were
examined in 40 boys with ASD, broad spectrum of intellectual abilities (63 < IQ <
127) and 44 typically developing (TD) boys, aged 6-15 years. The stimuli of small
(1 degrees ) and large (12 degrees ) radius were presented under high (100%) and
low (1%) contrast conditions. Social Responsiveness Scale and Sensory Profile
Questionnaire were used to assess the autism severity and sensory processing
abnormalities. We found that the SS index was atypically reduced, while SF index
abnormally enhanced in children with ASD. The presence of abnormally enhanced SF
in children with ASD was the only consistent finding between our study and that
of Foss-Feig et al. While the SS and SF indexes were strongly interrelated in TD
participants, this correlation was absent in their peers with ASD. In addition,
the SF index but not the SS index correlated with the severity of autism and the
poor registration abilities. The pattern of results is partially consistent with
the idea of hypofunctional inhibitory transmission in visual areas in ASD.
Nonetheless, the absence of correlation between SF and SS indexes paired with a
strong direct link between abnormally enhanced SF and autism symptoms in our ASD
sample emphasizes the role of the enhanced excitatory influences by themselves in
the observed abnormalities in low-level visual phenomena found in ASD.
PMID- 28405184
TI - Optical Imaging of the Motor Cortex Following Antidromic Activation of the
Corticospinal Tract after Spinal Cord Injury.
AB - Spinal cord injury (SCI) disrupts neuronal networks of ascending and descending
tracts at the site of injury, leading to a loss of motor function. Restoration
and new circuit formation are important components of the recovery process, which
involves collateral sprouting of injured and uninjured fibers. The present study
was conducted to determine cortical responses to antidromic stimulation of the
corticospinal tracts, to compare changes in the reorganization of neural pathways
within normal and spinal cord-injured rats, and to elucidate differences in
spatiotemporal activity patterns of the natural progression and reorganization of
neural pathways in normal and SCI animals using optical imaging. Optical signals
were recorded from the motor cortex in response to electrical stimulation of the
ventral horn of the L1 spinal cord. Motor evoked potentials (MEPs) were evaluated
to demonstrate endogenous recovery of physiological functions after SCI. A
significantly shorter N1 peak latency and broader activation in the MEP optical
recordings were observed at 4 weeks after SCI, compared to 1 week after SCI.
Spatiotemporal patterns in the cerebral cortex differed depending on functional
recovery. In the present study, optical imaging was found to be useful in
revealing functional changes and may reflect conditions of reorganization and/or
changes in surviving neurons after SCI.
PMID- 28405185
TI - Motor Stereotypies: A Pathophysiological Review.
AB - Motor stereotypies are common, repetitive, rhythmic movements with typical onset
in early childhood. While most often described in children with autism spectrum
disorder (ASD) and intellectual disability (ID), stereotypies can also present
without developmental delay and persist into adulthood. Stereotypies are often
disruptive and harmful, both physically and socially, and effective evidence
based treatments are lacking. This can be attributed, in part, to our incomplete
knowledge of the underlying biological and environmental risk. Several studies
implicate various neurotransmitters, brain circuits, anatomical loci, and pre-
and post-natal environmental influences in stereotypy onset and symptom severity.
However, there are few points of convergence among a relatively small number of
studies, indicating that more research is needed to confirm the underlying bases
of risk. Of particular note is the lack of published genetic studies of
stereotypies, despite evidence for Mendelian inheritance patterns in some
families. Focusing future studies on typically-developing children with primary
motor stereotypies may be a useful approach to minimize potential biological,
environmental, and genetic heterogeneity that could theoretically hinder
consistent findings. Ultimately, a deeper understanding of the underlying biology
and risk factors for motor stereotypies will lead us closer to more effective
targeted therapies that will alleviate suffering in affected children.
PMID- 28405186
TI - Color Representation Is Retinotopically Biased but Locally Intermingled in Mouse
V1.
AB - Dichromatic vision is common in many mammals. However, color processing in the
primary visual cortex (V1) of dichromatic mammals is relatively unknown compared
to the trichromatic primates. In this study, we investigated the functional
organization of color processing in mouse V1. The mouse retina has a graded
expression pattern of two opsins along its dorsoventral axis. However, it is not
clear whether and how this expression pattern is reflected in the cortical
representation at local (several hundred microns) and areal (V1) level. Using in
vivo two-photon calcium (Ca2+) imaging and wide-field Ca2+ imaging, we revealed
that V1 neurons responded to S (UV)- and M (green)-opsin isolating stimuli with
slightly biased color preference depending on retinotopic position in V1. This
was consistent with the distribution of retinal opsins. At the cellular level,
preferences for S- and M-opsin isolating stimuli were intermingled in a local
region encompassing several hundred microns. These results suggest that
functional organizations of color information are locally intermingled, but
slightly biased depending on the retinotopic position in mouse V1.
PMID- 28405188
TI - Compound 19e, a Novel Glucokinase Activator, Protects against Cytokine-Induced
Beta-Cell Apoptosis in INS-1 Cells.
AB - Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was
identified as a potent glucokinase activator (GKA) and showed a glucose-lowering
effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were
evaluated in INS-1 pancreatic beta-cells co-treated with TNF-alpha and IL-1beta
to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced
cell death, and the effect was similar to treatment with another GKA or exendin
4. Compound 19e reduced annexin-V stained cells and the expression of cleaved
caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the
expression of B-cell lymphoma-2 protein. Compound 19e inhibited apoptotic
signaling via induction of the ATP content, and the effect was correlated with
the downregulation of nuclear factor-kappaB p65 and inducible nitric oxide
synthase. Further, 19e increased NAD-dependent protein deacetylase sirtuin-1
(SIRT1) deacetylase activity, and the anti-apoptotic effect of 19e was attenuated
by SIRT1 inhibitor or SIRT1 siRNA treatment. Our results demonstrate that the
novel GKA, 19e, prevents cytokine-induced beta-cell apoptosis via SIRT1
activation and has potential as a therapeutic drug for the preservation of
pancreatic beta-cells.
PMID- 28405187
TI - Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon
degus.
AB - The accumulation of redox-active transition metals in the brain and metal
dyshomeostasis are thought to be associated with the etiology and pathogenesis of
several neurodegenerative diseases, and Alzheimer's disease (AD) in particular.
As well, distinct biometal imaging and role of metal uptake transporters are
central to understanding AD pathogenesis and aging but remain elusive, due
inappropriate detection methods. We therefore hypothesized that Octodon degus
develop neuropathological abnormalities in the distribution of redox active
biometals, and this effect may be due to alterations in the expression of
lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs
and ZIPs). Herein, we report the distribution profile of biometals in the aged
brain of the endemic Chilean rodent O. degus-a natural model to investigate the
role of metals on the onset and progression of AD. Using laser ablation
inductively coupled plasma mass spectrometry, our quantitative images of
biometals (Fe, Ca, Zn, Cu, and Al) appear significantly elevated in the aged O.
degus and show an age-dependent rise. The metals Fe, Ca, Zn, and Cu were
specifically enriched in the cortex and hippocampus, which are the regions where
amyloid plaques, tau phosphorylation and glial alterations are most commonly
reported, whilst Al was enriched in the hippocampus alone. Using whole brain
extracts, age-related deregulation of metal trafficking pathways was also
observed in O. degus. More specifically, we observed impaired lysosomal function,
demonstrated by increased cathepsin D protein expression. An age-related
reduction in the expression of subunit B2 of V-ATPase, and significant increases
in amyloid beta peptide 42 (Abeta42), and the metal transporter ATP13a2 were also
observed. Although the protein expression levels of the zinc transporters, ZnT
(1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O. degus,
ZnT10, decreased. Although no significant age-related change was observed for the
major iron/copper regulator IRP2, we did find a significant increase in the
expression of DMT1, a major transporter of divalent metal species, 5'
aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS. Collectively,
our data indicate that transition metals may be enriched with age in the brains
of O. degus, and metal dyshomeostasis in specific brain regions is age-related.
PMID- 28405189
TI - Corrigendum: Brief Report: A Preference for Biological Motion Predicts a
Reduction in Symptom Severity 1 Year Later in Preschoolers with Autism Spectrum
Disorders.
AB - [This corrects the article on p. 143 in vol. 7, PMID: 27605914.].
PMID- 28405191
TI - Cognitive Architecture with Evolutionary Dynamics Solves Insight Problem.
AB - In this paper, we show that a neurally implemented a cognitive architecture with
evolutionary dynamics can solve the four-tree problem. Our model, called
Darwinian Neurodynamics, assumes that the unconscious mechanism of problem
solving during insight tasks is a Darwinian process. It is based on the evolution
of patterns that represent candidate solutions to a problem, and are stored and
reproduced by a population of attractor networks. In our first experiment, we
used human data as a benchmark and showed that the model behaves comparably to
humans: it shows an improvement in performance if it is pretrained and primed
appropriately, just like human participants in Kershaw et al. (2013)'s
experiment. In the second experiment, we further investigated the effects of
pretraining and priming in a two-by-two design and found a beginner's luck type
of effect: solution rate was highest in the condition that was primed, but not
pretrained with patterns relevant for the task. In the third experiment, we
showed that deficits in computational capacity and learning abilities decreased
the performance of the model, as expected. We conclude that Darwinian
Neurodynamics is a promising model of human problem solving that deserves further
investigation.
PMID- 28405190
TI - Abnormal Visual Scanning of Emotionally Evocative Natural Scenes in Huntington's
Disease.
AB - Huntington's disease (HD) is a neurodegenerative movement disorder associated
with deficits in the processing of emotional stimuli, including alterations in
the self-reported subjective experience of emotion when presented with pictures
of emotional scenes. The aim of this study was to determine whether individuals
with HD, compared to unaffected controls, display abnormal visual scanning of
emotionally evocative natural scenes. Using eye-tracking, we recorded eye
movements of 25 HD participants (advanced pre-symptomatic and early symptomatic)
and 25 age-matched unaffected control participants during a picture viewing task.
Participants viewed pictures of natural scenes associated with different
emotions: anger, fear, disgust, happiness, or neutral, and evaluated those
pictures on a valence rating scale. Individuals with HD displayed abnormal visual
scanning patterns, but did not differ from controls with respect to their valence
ratings. Specifically, compared to controls, HD participants spent less time
fixating on the pictures and made longer scan paths. This finding highlights the
importance of taking visual scanning behavior into account when investigating
emotion processing in HD. The visual scanning patterns displayed by HD
participants could reflect a heightened, but possibly unfocussed, search for
information, and might be linked to attentional deficits or to altered subjective
emotional experiences in HD. Another possibility is that HD participants may have
found it more difficult than controls to evaluate the emotional valence of the
scenes, and the heightened search for information was employed as a compensatory
strategy.
PMID- 28405192
TI - Induction of Osteopontin by Dengue Virus-3 Infection in THP-1 Cells: Inhibition
of the Synthesis by Brefelamide and Its Derivative.
AB - Osteopontin (OPN) is a multifunctional matricellular protein produced by a broad
range of cells including osteoclasts, macrophages, T cells, endothelial cells,
and vascular smooth muscle cells. OPN modulates various physiological and
pathological events such as inflammation, wound healing, and bone formation and
remodeling. Dengue virus (DENV) infection causes an increase in plasma OPN
levels, which is correlated with the severity of symptoms and coagulation
abnormalities. DENV infection also induces OPN gene expression in human
macrophages. This study investigated the inhibitory effects of brefelamide and
its methyl ether derivative on DENV-3 by measuring changes in OPN levels in human
THP-1 and 293T cell lines infected at different multiplicities of infection and
post-infection time points. OPN mRNA expression and viral RNA were detected by
reverse transcriptase quantitative real-time PCR, whereas protein level was
determined by enzyme-linked immunosorbent assay. We found that viral copy number
was higher in 293T than in THP-1 cells. However, THP-1 constitutively expressed
higher levels of OPN mRNA and protein, which were enhanced by DENV-3 infection.
Brefelamide and its derivative suppressed OPN production in DENV-3 infected THP-1
cells; the effective doses of these compounds had no effect on uninfected cells,
indicating low cytotoxicity. These results suggest that brefelamide and its
methyl ether derivative have therapeutic effects in preventing inflammation,
coagulopathy, and fibrinolysis caused by OPN upregulation induced by DENV-3
infection.
PMID- 28405193
TI - The Efficacy of Isolated Bacteriophages from Pig Farms against ESBL/AmpC
Producing Escherichia coli from Pig and Turkey Farms.
AB - Extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases are plasmid
(but also chromosomally) encoded enzymes found in Enterobacteriaceae, determining
resistance to a variety of important antibiotics including penicillins,
cephalosporins, and monobactams. In recent decades, the prevalence of ESBL/AmpC
producing bacteria has increased rapidly across the world. Here, we evaluate the
potential use of bacteriophages in terms of a reduction of antibiotic-resistant
bacteria in healthy animals. The aim of our studies was to isolate bacteriophages
capable of destroying ESBL/AmpC-producing Escherichia coli isolated from
livestock habitats. The efficacy of isolated phages against ESBL/AmpC E. coli
strains varies, but creation of a phage cocktail with broad activity spectrum is
possible. This may indicate that the role of phages may not be limited to phage
therapy, but bacterial viruses may also be applied against spread of bacteria
with antibiotic resistance genes in the environment. We also addressed the
hypothesis, that phages, effective for therapeutic purposes may be isolated from
distant places and even from different environments other than the actual
location of the targeted bacteria. This may be beneficial for practical purposes,
as the construction of effective phage preparations does not require access to
disease outbreaks.
PMID- 28405195
TI - Corrigendum: Agonistic Anti-PDGF Receptor Autoantibodies from Patients with
Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In
Vitro.
AB - [This corrects the article on p. 75 in vol. 8, PMID: 28228756.].
PMID- 28405196
TI - Corrigendum: Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a
Murine Model Resembling Human Lupus.
AB - [This corrects the article on p. 396 in vol. 7, PMID: 27746783.].
PMID- 28405194
TI - Modeling Natural Killer Cell Targeted Immunotherapies.
AB - Animal models have extensively contributed to our understanding of human
immunobiology and to uncover the underlying pathological mechanisms occurring in
the development of diseases. However, mouse models do not reproduce the genetic
and molecular complexity inherent in human disease conditions. Human immune
system (HIS) mouse models that are susceptible to human pathogens and can
recapitulate human hematopoiesis and tumor immunobiology provide one means to
bridge the interspecies gap. Natural killer cells are the founding member of the
innate lymphoid cell family. They exert a rapid and strong immune response
against tumor and pathogen-infected cells. Their antitumor features have long
been exploited for therapeutic purposes in the context of cancer. In this review,
we detail the development of highly immunodeficient mouse strains and the models
currently used in cancer research. We summarize the latest improvements in
adoptive natural killer (NK) cell therapies and the development of novel NK cell
sources. Finally, we discuss the advantages of HIS mice to study the interactions
between human NK cells and human cancers and to develop new therapeutic
strategies.
PMID- 28405197
TI - Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites.
AB - Plants play an essential part in global carbon fixing through photosynthesis and
are the primary food and energy source for humans. Understanding them thoroughly
is therefore of highest interest for humanity. Advances in DNA and RNA sequencing
and in protein and metabolite analysis allow the systematic description of plant
composition at the molecular level. With imaging mass spectrometry, we can now
add a spatial level, typically in the micrometer-to-centimeter range, to their
compositions, essential for a detailed molecular understanding. Here we present
an LC-MS based approach for 3D plant imaging, which is scalable and allows the
analysis of entire plants. We applied this approach in a case study to pepper and
tomato plants. Together with MS/MS spectra library matching and spectral
networking, this non-targeted workflow provides the highest sensitivity and
selectivity for the molecular annotations and imaging of plants, laying the
foundation for studies of plant metabolism and plant-environment interactions.
PMID- 28405198
TI - Mapping Water Stress Incidence and Intensity, Optimal Plant Populations, and
Cultivar Duration for African Groundnut Productivity Enhancement.
AB - Groundnut production is limited in Sub-Saharan Africa and water deficit or
"drought," is often considered as the main yield-limiting factor. However, no
comprehensive study has assessed the extent and intensity of "drought"-related
yield decreases, nor has it explored avenues to enhance productivity. Hence, crop
simulation modeling with SSM (Simple Simulation Modeling) was used to address
these issues. To palliate the lack of reliable weather data as input to the
model, the validity of weather data generated by Marksim, a weather generator,
was tested. Marksim provided good weather representation across a large gradient
of rainfall, representative of the region, and although rainfall generated by
Marksim was above observations, run-off from Marksim data was also higher, and
consequently simulations using observed or Marksim weather agreed closely across
this gradient of weather conditions (root mean square of error = 99 g m-2; R2 =
0.81 for pod yield). More importantly, simulation of yield changes upon agronomic
or genetic alterations in the model were equally predicted with Marksim weather.
A 1 degrees * 1 degrees grid of weather data was generated. "Drought"-related
yield reduction were limited to latitudes above 12-13 degrees North in West
Central Africa (WCA) and to the Eastern fringes of Tanzania and Mozambique in
East South Africa (ESA). Simulation and experimental trials also showed that
doubling the sowing density of Spanish cultivars from 20 to 40 plants m-2 would
increase yield dramatically in both WCA and ESA. However, increasing density
would require growers to invest in more seeds and likely additional labor. If
these trade-offs cannot be alleviated, genetic improvement would then need to re
focus on a plant type that is adapted to the current low sowing density, like a
runner rather than a bush plant type, which currently receives most of the
genetic attention. Genetic improvement targeting "drought" adaptation should also
be restricted to areas where water is indeed an issue, i.e., above 12-13 degrees
N latitude in WCA and the Eastern fringes of Tanzania and Mozambique.
PMID- 28405200
TI - Corrigendum: Loop-Mediated Isothermal Amplification Method for the Rapid
Detection of Ralstonia solanacearum Phylotype I Mulberry Strains in China.
AB - [This corrects the article on p. 76 in vol. 8, PMID: 28197157.].
PMID- 28405201
TI - Interleukin 8 (-251 T>A) polymorphism in children and teenagers infected with
Helicobacter pylori.
AB - BACKGROUND: Helicobacter pylori (H. pylori) is a gram-negative bacterium that
colonizes the human stomach and causes a variety of gastric diseases. This study
evaluated the correlations between the -251 (T>A) (rs4073) polymorphism of
interleukin-8 (IL-8), the etiology of gastric disease, and H. pylori infection in
pediatric and adolescent patients. METHODS: DNA samples were obtained from 285
gastric biopsies from pediatric patients. H. pylori was detected by PCR, whereas
PCR-RFLP was used to characterize the -251 (T>A) polymorphism of IL-8. RESULTS:
The histological analysis revealed the presence of gastritis in 158 patients
(55.44%). H. pylori was found in 71 samples (24.9%). The -251 (T>A) polymorphism
revealed that 58 (29.47%) samples were TT, 143 (50.18%) samples were TA, and 84
(20.35%) samples were AA. CONCLUSIONS: Our findings suggest that IL8-251 A allele
may be an important risk factor for the development of gastric disease when
associated with H. pylori infection.
PMID- 28405199
TI - Comparative Analysis of Expression Profiles of Panicle Development among Tolerant
and Sensitive Rice in Response to Drought Stress.
AB - Water deficit caused a serious threat to crops, especially panicle development at
reproductive growth phase. We investigated grain yield components and gene
expression profiles of panicle among tolerant and sensitive rice in response to
drought stress. Panicle morphologies exhibited that secondary branches per
panicle were more severely affected as compared to primary branches per panicle.
Moreover, grain weight per panicle showed significant decrease for both tolerant
and sensitive varieties except for MILT1444. Expression profile analysis revealed
that 783 differentially expressed genes (DEGs) were identified to be drought
induced from young panicles in 2 cm length. Hierarchical clustering indicated
that 76.8% of DEGs were up-regulated for all six rice varieties, and the
percentage of down-regulated genes was higher in sensitive group than tolerant
group. Biological process category revealed that the shared Gene Ontology (GO)
terms were involved in response to abiotic stimulus and stress, whereas the
specific GO terms in tolerant group were identified as regulation of biological
quality, homeostatic process, cell growth, anatomical structure morphogenesis and
development, and the unique terms in sensitive varieties were identified as lipid
metabolic process and secondary metabolic process. Furthermore, the gene-based
association analysis narrowed down list of DEGs, and four genes common to all six
varieties were selected as candidate for breeders. Together, we found several
shared and distinct biological processes between tolerant and sensitive
varieties, and candidate stress-responsive genes. These findings provided insight
into functional mechanisms regulating drought stress response in panicle
development and may also help to crop tolerant improvement.
PMID- 28405202
TI - Diagnosis and treatment of hereditary hemorrhagic telangiectasia in a pediatric
patient with chronic cyanosis.
PMID- 28405203
TI - The chest x-ray in congenital heart disease 7.
PMID- 28405204
TI - Aortic arch tortuosity with PHACE syndrome - a rare case scenario.
AB - PHACE syndrome is a rare neurocutaneous disorder characterised by an association
of infantile haemangiomas with structural anomalies of brain, cerebral
vasculature, eye, aorta and chest wall.1 Coarctation of aorta (COA) is most the
common cardiac anomaly reported in PHACE syndrome. COA or interrupted aortic arch
in PHACE is unique and complex both in location and character compared to the
typical coarctation anatomy. Arterial tortuosity of the cerebral vasculature has
been well described in literature in PHACE syndrome. We present a rare case of
tortuous aortic arch continuing as descending aorta in an infant with PHACE
syndrome.
PMID- 28405205
TI - 3 year old with chronic wet cough: Intralobar Bronchopulmonary sequestration.
PMID- 28405206
TI - Aortic stenting for neonatal coarctation of the aorta - when should this be
considered?
PMID- 28405207
TI - Association of unicuspid unicommissural aortic valve and complex congenital heart
disease depicted by cardiac magnetic resonance.
PMID- 28405208
TI - A case of atypical Kawasaki disease with giant coronary artery aneurysm
containing thrombus.
AB - INTRODUCTION: Kawasaki disease (KD) is an acute febrile, systemic vasculitic
syndrome of unknown etiology, occurring primarily in children younger than 5
years of age. Administration of IVIG within the first 10 days after onset of
fever in combination with high dose aspirin reduces the risk of coronary artery
damage in KD. Though rare, giant aneurysms of the coronary arteries may develop
in untreated cases and prove extremely challenging to manage. CASE PRESENTATION:
A 9-month-old Caucasian boy presented to our paediatric emergency department with
a 4-week history of intermittent pyrexia and irritability. Typical mucocutaneous
signs of Kawasaki Disease were absent upon presentation. A trans-thoracic
echocardiogram identified a giant aneurysm of the left anterior descending artery
with thrombus formation in-situ and the child was managed with intravenous
immunoglobulin, steroids, high dose aspirin therapy and later warfarinisation.
DISCUSSION: Cardiovascular sequelae of Kawasaki disease include giant coronary
artery aneurysms with thrombosis. Enlargement of a coronary aneurysm after the
acute phase of Kawasaki disease is uncommon and the outcome of interventional
approaches poorly studied.
PMID- 28405209
TI - Tuberous sclerosis associated with multiple hepatic lipomatous tumours.
PMID- 28405210
TI - Y Chromosome in Tumer syndrome; a case report.
PMID- 28405211
TI - Low rate of initiation and short duration of breastfeeding in a maternal and
infant home visiting project targeting rural, Southern, African American women.
AB - BACKGROUND: Despite the benefits of breastfeeding for both infant and mother,
rates in the United States remain below Healthy People 2020 breastfeeding
objectives. This paper describes breastfeeding outcomes of the Delta Healthy
Sprouts participants during gestational and postnatal periods. Of specific
interest was whether breastfeeding intent, knowledge, and beliefs changed from
the early to late gestational period. Additionally, analyses were conducted to
test for associations between breastfeeding initiation and breastfeeding intent,
knowledge and beliefs as well as sociodemographic characteristics and other
health measures. METHODS: Eighty-two pregnant women were enrolled in this project
spanning three Mississippi counties. Participants were randomly assigned to one
of two treatment groups. Because both groups received information about
breastfeeding, breastfeeding outcomes were analyzed without regard to treatment
assignment. Hence participants were classified into two groups, those that
initiated breastfeeding and those that did not initiate breastfeeding.
Generalized linear mixed models were used to test for significant group, time,
and group by time effects on breastfeeding outcomes. RESULTS: Breastfeeding
knowledge scores increased significantly from baseline to late gestational period
for both groups. Across time, breastfeeding belief scores were higher for the
group that initiated breastfeeding as compared to the group that did not
breastfeed. Only 39% (21 of 54) of participants initiated breastfeeding. Further,
only one participant breastfed her infant for at least six months. Breastfeeding
intent and beliefs as well as pre-pregnancy weight class significantly predicted
breastfeeding initiation. CONCLUSIONS: Our findings indicate that increasing
knowledge about and addressing barriers for breastfeeding were insufficient to
empower rural, Southern, primarily African American women to initiate or continue
breastfeeding their infants. Improving breastfeeding outcomes for all
socioeconomic groups will require consistent, engaging, culturally relevant
education that positively influences beliefs as well as social and environmental
supports that make breastfeeding the more accepted, convenient, and economical
choice for infant feeding. TRIAL REGISTRATION: clinicaltrials.gov NCT01746394.
Registered 5 December 2012.
PMID- 28405213
TI - Infant feeding knowledge, perceptions and practices among women with and without
HIV in Johannesburg, South Africa: a survey in healthcare facilities.
AB - BACKGROUND: South Africa has a history of low breastfeeding rates among women
with and without Human Immunodeficiency Virus (HIV). In this study, we assessed
infant feeding knowledge, perceptions and practices among pregnant and postpartum
women with and without HIV, in the context of changes in infant feeding and
Prevention of Mother-to-Child Transmission of HIV (PMTCT) guidelines. METHODS:
This was a cross-sectional survey conducted from April 2014 to March 2015 in 10
healthcare facilities in Johannesburg, South Africa. A total of 190 pregnant and
180 postpartum women (74 and 67, respectively, were HIV positive) were
interviewed using a semi-structured questionnaire. Multiple regression analyses
assessed factors associated with an intention to exclusively breastfeed, and
exclusive breastfeeding of infants less than six months of age. RESULTS: Women
with HIV had better overall knowledge on safe infant feeding practices, both in
general and in the context of HIV infection. There were however gaps in knowledge
among women with and without HIV. Information from healthcare facilities was the
main source of information for all groups of women in the study. A greater
percentage of women without HIV 80.9% (93/115), reported an intention to
exclusively breastfeed, compared to 64.9% (48/74) of women with HIV, p = 0.014.
Not having HIV was positively associated with a reported intention to breastfeed,
Adjusted Odds Ratio (AOR) 3.60, 95% CI 1.50, 8.62. Other factors associated with
a reported intention to exclusively breastfeed were prior breastfeeding
experience and higher knowledge scores on safe infant feeding practices in the
context of HIV infection. Among postpartum women, higher scores on general
knowledge of safe infant feeding practices were positively associated with
reported exclusive breastfeeding, AOR 2.18, 95% CI 1.52, 3.12. Most women
perceived that it was difficult to exclusively breastfeed and that cultural
factors were a barrier to exclusive breastfeeding. CONCLUSIONS: While a greater
proportion of women are electing to breastfeed, HIV infection and cultural
factors remain an important influence on safe infant feeding practices.
Healthcare workers are the main source of information, and highlight the need for
accurate and consistent messaging for both women with and without HIV.
PMID- 28405214
TI - A real-time phenotyping framework using machine learning for plant stress
severity rating in soybean.
AB - BACKGROUND: Phenotyping is a critical component of plant research. Accurate and
precise trait collection, when integrated with genetic tools, can greatly
accelerate the rate of genetic gain in crop improvement. However, efficient and
automatic phenotyping of traits across large populations is a challenge; which is
further exacerbated by the necessity of sampling multiple environments and
growing replicated trials. A promising approach is to leverage current advances
in imaging technology, data analytics and machine learning to enable automated
and fast phenotyping and subsequent decision support. In this context, the
workflow for phenotyping (image capture -> data storage and curation -> trait
extraction -> machine learning/classification -> models/apps for decision
support) has to be carefully designed and efficiently executed to minimize
resource usage and maximize utility. We illustrate such an end-to-end phenotyping
workflow for the case of plant stress severity phenotyping in soybean, with a
specific focus on the rapid and automatic assessment of iron deficiency chlorosis
(IDC) severity on thousands of field plots. We showcase this analytics framework
by extracting IDC features from a set of ~4500 unique canopies representing a
diverse germplasm base that have different levels of IDC, and subsequently
training a variety of classification models to predict plant stress severity. The
best classifier is then deployed as a smartphone app for rapid and real time
severity rating in the field. RESULTS: We investigated 10 different
classification approaches, with the best classifier being a hierarchical
classifier with a mean per-class accuracy of ~96%. We construct a phenotypically
meaningful 'population canopy graph', connecting the automatically extracted
canopy trait features with plant stress severity rating. We incorporated this
image capture -> image processing -> classification workflow into a smartphone
app that enables automated real-time evaluation of IDC scores using digital
images of the canopy. CONCLUSION: We expect this high-throughput framework to
help increase the rate of genetic gain by providing a robust extendable framework
for other abiotic and biotic stresses. We further envision this workflow embedded
onto a high throughput phenotyping ground vehicle and unmanned aerial system that
will allow real-time, automated stress trait detection and quantification for
plant research, breeding and stress scouting applications.
PMID- 28405212
TI - Prevalence and determinants of cessation of exclusive breastfeeding in the early
postnatal period in Sydney, Australia.
AB - BACKGROUND: Optimal breastfeeding has benefits for the mother-infant dyads. This
study investigated the prevalence and determinants of cessation of exclusive
breastfeeding (EBF) in the early postnatal period in a culturally and
linguistically diverse population in Sydney, New South Wales, Australia. METHODS:
The study used routinely collected perinatal data on all live births in 2014 (N =
17,564) in public health facilities in two Local Health Districts in Sydney,
Australia. The prevalence of mother's breastfeeding intention, skin-to-skin
contact, EBF at birth, discharge and early postnatal period (1-4 weeks postnatal)
were estimated. Multivariate logistic regression models that adjusted for
confounders were conducted to determine association between cessation of EBF in
the early postnatal period and socio-demographic, psychosocial and health service
factors. RESULTS: Most mothers intended to breastfeed (92%), practiced skin-to
skin contact (81%), exclusively breastfed at delivery (90%) and discharge (89%).
However, the prevalence of EBF declined (by 27%) at the early postnatal period
(62%). Younger mothers (<20 years) and mothers who smoked cigarettes in pregnancy
were more likely to cease EBF in the early postnatal period compared to older
mothers (20-39 years) and those who reported not smoking cigarettes, respectively
[Adjusted Odds Ratio (AOR) =2.7, 95%CI 1.9-3.8, P <0.001 and AOR = 2.5, 95%CI 2.1
3.0, P <0.001, respectively]. Intimate partner violence, assisted delivery, low
socio-economic status, pre-existing maternal health problems and a lack of
partner support were also associated with early cessation of EBF in the postnatal
period. CONCLUSIONS: Our findings suggest that while most mothers intend to
breastfeed, and commence EBF at delivery and at discharge, the maintenance of EBF
in the early postnatal period is sub-optimal. This highlights the need for
efforts to promote breastfeeding in the wider community along with targeted
actions for disadvantaged groups and those identified to be at risk of early
cessation of EBF to maximise impact.
PMID- 28405215
TI - The American Psychosomatic Society - integrating mind, brain, body and social
context in medicine since 1942.
AB - BACKGROUND: The American Psychosomatic Society is one of the oldest and probably
the most influential scientific society in psychosomatic/biopsychosocial research
worldwide. The current article delineates the historical development and current
strategic orientation of the society. METHOD: Review of published literature,
archived materials and current documents of the society. RESULTS: The American
Psychosomatic Society (APS) was founded in 1942, originally named the "American
Society for Research in Psychosomatic Problems ". It originated from the
editorial board of the Journal Psychosomatic Medicine, which had already been
founded in 1939 and has become one of the major journals in the field. As an
organization, APS has developed into a premier international scientific society,
providing an interdisciplinary home for researchers from medicine, psychology and
related areas, gathering under the mission "to advance and integrate the
scientific study of biological, psychological, behavioral and social factors in
health and disease" and dedicated to the goals of Scientific Excellence, Clinical
Relevance, and Vibrant and Diverse Membership. Besides editing Psychosomatic
Medicine, the APS organizes Annual Meetings and specialized events, issues
several scientific awards and scholarships and is engaged in collaborative
efforts to improve the research and funding landscape for biobehavioral research
in the US and translate psychosomatic research findings into medical education
and clinical practice. CONCLUSION: In its 75th anniversary year, the American
Psychosomatic Society has developed into the scientific landscape of the 21st
century, and its current updated strategy addresses contemporary demands in
advancing science and improving holistic patient care.
PMID- 28405216
TI - Effect of a mental health training programme on Nigerian school pupils'
perceptions of mental illness.
AB - BACKGROUND: Stigmatizing attitudes and discriminatory behaviour towards persons
with mental illness are known to start in childhood. In Nigeria, it is not
unusual to see children taunting persons with mental illness. This behaviour
continues into adulthood as evidenced by the day-to-day occurrences in the
community of negative attitudes and social distance from persons with mental
illness. School-based interventions for pupils have been found to increase
knowledge about mental illness. Children are recognised as potential agents of
change bringing in new ways of thinking. This study determined the effect of a 3
day mental health training for school pupils in Southwest Nigeria, on the
perceptions of and social distance towards persons with mental illness. METHODS:
A total of 205 school pupils drawn from two administrative wards were randomly
assigned to control and experimental groups. The mean age of the pupils was 14.91
years (+/-1.3). The pupils in the intervention group received a 5-h mental health
training session spaced out over 3-days. Apart from didactic lectures, case
history presentations and discussions and role-play were part the training.
Outcome measures were rated using a knowledge, attitude and social distance
questionnaire at baseline, immediately following the training for both group and
3-week post intervention for the intervention group. A Student Evaluation Form
was administered to evaluate the pupils' assessment of the training programme.
Frequencies, Chi square statistics, paired t test were used to analyse the data
received. RESULTS: At immediate post-intervention, the intervention group had a
significantly higher mean knowledge score compared to controls, 21.1 vs. 22.0; p
= 0.097 to 26.1 vs 22.0; p < 0.01. Respondents in the intervention group had a
higher mean attitude score of 5.8 compared to 5.6 in the control group although
this was not statistically significant (p < 0.627). Comparisons within the
intervention group from baseline to immediate post-intervention showed a
significant increase in mean knowledge and attitude scores of respondents, 21.0
26.2: p < 0.001 and 4.8-5.8; p = 0.004 respectively. This change was sustained at
3 weeks post intervention. The majority (98.8%) noted that the training was
useful to them. CONCLUSIONS: Multiple contacts and mixed-method training sessions
produced a positive and sustained change in knowledge of and attitude towards
persons with mental illness in school pupils in Nigeria.
PMID- 28405217
TI - Bioprocessing of tea oil fruit hull with acetic acid organosolv pretreatment in
combination with alkaline H2O2.
AB - BACKGROUND: As a natural renewable biomass, the tea oil fruit hull (TOFH) mainly
consists of lignocellulose, together with some bioactive substances. Our earlier
work constructed a two-stage solvent-based process, including one aqueous ethanol
organosolv extraction and an atmospheric glycerol organosolv (AGO) pretreatment,
for bioprocessing of the TOFH into diverse bioproducts. However, the AGO
pretreatment is not as selective as expected in removing the lignin from TOFH,
resulting in the limited delignification and simultaneously high cellulose loss.
RESULTS: In this study, acetic acid organosolv (AAO) pretreatment was optimized
with experimental design to fractionate the TOFH selectively. Alkaline hydrogen
peroxide (AHP) pretreatment was used for further delignification. Results
indicate that the AAO-AHP pretreatment had an extremely good selectivity at
component fractionation, resulting in 92% delignification and 88% hemicellulose
removal, with 87% cellulose retention. The pretreated substrate presented a
remarkable enzymatic hydrolysis of 85% for 48 h at a low cellulase loading of 3
FPU/g dry mass. The hydrolyzability was correlated with the composition and
structure of substrates by using scanning electron microscopy, confocal laser
scanning microscopy, and X-ray diffraction. CONCLUSION: The mild AAO-AHP
pretreatment is an environmentally benign and advantageous scheme for biorefinery
of the agroforestry biomass into value-added bioproducts.
PMID- 28405219
TI - Braided tape is equivalent to modified Mason-Allen multi-strand #2 suture in
subscapularis muscle repair: results of a biomechanical study.
AB - BACKGROUND: To help determine the optimal fixation method for subscapularis
tendon repair in arthroplasty, the present study compares single-passage
transosseous tape (BT) and modified Mason-Allen #2 suture (MA). METHODS: Eighteen
human cadaveric shoulders were randomized to two repair constructs after
arthroplasty preparation. Both techniques included two transosseous passages
through the bicipital groove and then through the tendon at the level of the
anatomical neck. Construct was tested using a traction machine, measuring cyclic
loading and ultimate load to failure. RESULTS: The mean age of our specimens was
71 years. No significant difference was observed between the repair techniques in
both mean ultimate load and cyclic loading. The mean (SD) ultimate load (UL) for
BT was 293 (84) N and 342 (117) N for MA, which was not statistically significant
(p = 0.374). The majority of repairs failed in the tendon. Bone cut-out was
observed with the MA but not for the BT repair. No correlation was found between
bone density and UL for BT (r = -0.09) but there was strong correlation for MA (r
= 0.63). CONCLUSIONS: The MA repair appears to be more dependant on bone mineral
density for ultimate load, indicating that braided-tape might be better suited
for osteoporotic patients to avoid bone cut-out.
PMID- 28405218
TI - Adhesive capsulitis of the shoulder: review of pathophysiology and current
clinical treatments.
AB - Adhesive shoulder capsulitis, or arthrofibrosis, describes a pathological process
in which the body forms excessive scar tissue or adhesions across the
glenohumeral joint, leading to pain, stiffness and dysfunction. It is a
debilitating condition that can occur spontaneously (primary or idiopathic
adhesive capsulitis) or following shoulder surgery or trauma (secondary adhesive
capsulitis). Here, we review the pathophysiology of adhesive shoulder capsulitis,
highlighting its clinical presentation, natural history, risk factors,
pathoanatomy and pathogenesis. Both current non-operative and operative
treatments for adhesive capsulitis are described, and evidence-based studies are
presented in support for or against each corresponding treatment. Finally, the
review also provides an update on the gene expression profile of adhesive
capsulitis and how this new understanding can help facilitate development of
novel pharmacological therapies.
PMID- 28405220
TI - Intraoperative complications during revision shoulder arthroplasty: a study using
the National Joint Registry dataset.
AB - BACKGROUND: The surgical options for revision shoulder arthroplasty and the
number of procedures performed are increasing. However, little is known about the
risk factors for intraoperative complications associated with this complex
surgery. METHODS: The National Joint Registry (NJR) is a surgeon reported
database recording information on major joint replacements including revision
shoulder arthroplasty. Using multivariable binary logistic regression modelling,
we analyzed 1445 revision shoulder arthroplasties reported to the NJR between
April 2012 and 2015. RESULTS: The risk of developing a complication during
revision surgery was greater than primary arthroplasty (5% versus 2.5%). An
intraoperative fracture was the most common complication occurring in 50 (3.5%)
cases. Nerve injuries were recorded for two (0.1%) patients and vascular injuries
for one (0.1%) patient. The incidence of intraoperative fractures was higher in
females than males (relative risk = 3.25; p = 0.005). Periprosthetic fracture as
an indication for revision carried the highest risk for any complication
(relative risk = 3.00, p = 0.06). CONCLUSIONS: This is the largest registry study
to date investigating the incidence and risk factors for intraoperative
complications during revision shoulder arthroplasty. Females have over three
times the risk of intraoperative fractures compared to males. This study will
help inform surgeons to accurately counsel patients.
PMID- 28405221
TI - Assessment of the restriction of arm elevation after intramedullary fixation for
proximal humeral fractures.
AB - BACKGROUND: Nail protrusion is suspected as a reason for the restriction of arm
elevation after antegrade nailing of proximal humeral fractures, although
assessment of the restriction of the glenohumeral joint during arm elevation has
been insufficient. METHODS: In this retrospective study, 30 shoulders with
proximal humeral fractures in 29 cases were treated with Polarus short nails
(Acumed, Beaverton, OR, USA). At a mean final follow-up of 14 months, clinical
outcomes, bony union, alignment including retroversion of the head and entry
points of the nails were evaluated. The ability of a subject to achieve maximum
elevation above the zero position was also evaluated. RESULTS: Constant and
Japanese Shoulder Association scores were a mean (SD) of 54 (12) and 71 (8.9)
points, respectively. Even though all cases achieved bony union without mal
alignment of the head and greater tuberosity height or protrusion of the nail at
its entry point, only six subjects could achieve maximum elevation above the zero
position. CONCLUSIONS: Based on these findings, treatment of proximal humeral
fractures with an antegrade humeral nail inserted from the top of the humeral
head results in restricted arm elevation, even in patients without nail
protrusion or fragment malalignment.
PMID- 28405222
TI - Triceps on approach for total elbow arthroplasty: worth preserving? A review of
approaches for total elbow arthroplasty.
AB - Total elbow arthroplasty can be a rewarding operation and is becoming
increasingly used in the elderly fracture population. Multiple approaches are
represented in the literature and deciding on the best approach is difficult.
This review discusses approaches and their reported outcomes, aiming to allow
surgeons to make an informed choice about which approach to use.
PMID- 28405223
TI - Electromyographic activity of the shoulder muscles during rehabilitation
exercises in subjects with and without subacromial pain syndrome: a systematic
review.
AB - BACKGROUND: Subacromial pain syndrome (SPS) is a common cause of shoulder pain
and muscle activity deficits are postulated to contribute to the development and
progression of the disorder. The purpose of this systematic review was to
definitively determine whether evidence exists of differences in electromyography
(EMG) characteristics between subjects with and without SPS. METHODS: Six key
databases were searched: MEDLINE, EMBASE, CINAHL, SPORTdiscus, PEDro and The
Cochrane Library (inception to May 2016). The search yielded 1414 records using
terms relating to shoulder impingement, EMG, scapular and rotator cuff muscles.
Twenty-two papers remained once duplicates were removed and selection criteria
applied. Data extraction, quality assessment and data synthesis were performed.
Effect sizes and 95% confidence intervals were calculated. RESULTS: There was
limited evidence that serratus anterior has lower amplitude, delayed activation
and earlier termination in SPS participants. For the majority of muscles,
regardless of task, load or arm position, significant differences were not
demonstrated or results were contradictory. CONCLUSIONS: The understanding of SPS
is changing and EMG appears unable to capture the complexities associated with
this condition. Addressing aberrant movement patterns and facilitating balanced
activation of all shoulder muscles may be a more appropriate treatment direction
for the future.
PMID- 28405224
TI - Level of patient-physician agreement in assessment of change following
conservative rehabilitation for shoulder pain.
AB - BACKGROUND: Assessment of health-related status has been shown to vary between
patients and physicians, although the degree of patient-physician discordance in
the assessment of the change in status is unknown. METHODS: Ninety-nine patients
with shoulder dysfunction underwent a standardized physician examination and
completed several self-reported questionnaires. All patients were prescribed the
same physical therapy intervention. Six weeks later, the patients returned to the
physician, when self-report questionnaires were re-assessed and the Global Rating
of Change (GROC) was completed by the patient. The physician completed the GROC
retrospectively. To determine agreement between patient and physician, intra
class correlation (ICC) coefficient and Pearson's r using the 15-point GROC and
weighted kappa using a consolidated three-point GROC were calculated. RESULTS:
Utilizing the 15-point GROC, complete agreement was observed in 37 of 99 patients
(37%). ICC and Pearson's r between patient and physician were 0.62 and 0.63,
respectively. Utilizing a consolidated three-point GROC, complete agreement was
observed in 76 of 99 patients (77%). Weighted kappa was 0.62. CONCLUSIONS:
Assessment of change reported by the patient demonstrates moderate to good
agreement with physician assessment. These findings indicate that the GROC does
reflect and represent similar assessment of change in health status by patients
and physicians. This can aid discussion of both past treatment results and future
treatment plans.
PMID- 28405225
TI - Use of flexible elbow reamers for cement removal in the humerus during revision
shoulder arthroplasty.
AB - Humeral cement removal in revision shoulder arthroplasty can be challenging.
Secondary damage to the bone and neighbouring structures can be extensive and
compromise later reconstruction. We present a technique that employs flexible
reamers from elbow arthroplasty instrumentation, which aids cement removal at the
same time as minimizing the risk of iatrogenic injury.
PMID- 28405226
TI - Assessment and decision making in the unstable elbow: management of simple
dislocations.
AB - Simple elbow dislocations are usually treated conservatively. Radiographs are
negative in simple dislocations. Results are generally good, although a small
percentage of patients may develop chronic instability. Ligamentous repair can be
indicated in high demand patients or if the elbow remains unstable following a
closed reduction. Chronic instability is classified per their direction. Surgery
is often indicated in the chronically unstable elbow.
PMID- 28405228
TI - Normal echocardiographic mitral and aortic valve thickness in children.
AB - OBJECTIVE: We aimed to define the normal range of aortic and mitral valve
thickness in healthy schoolchildren from a high prevalence rheumatic heart
disease (RHD) region, using a standardised protocol for imaging and measurement.
METHODS: Measurements were performed in 288 children without RHD. Anterior mitral
valve leaflet (AMVL) thickness measurements were performed at the midpoint and
tip of the leaflet in the parasternal long axis (PSLA) in diastole, when the AMVL
was approximately parallel to the ventricular septum. Thickness of the aortic
valve was measured from PSLA imaging in systole when the leaflets were at maximum
excursion. The right coronary and non-coronary closure lines of the aortic valve
were measured in diastole in parasternal short axis (PSSA) imaging. Results were
compared with 51 children with RHD classified by World Heart Federation
diagnostic criteria. RESULTS: In normal children, median AMVL tip thickness was
2.0 mm (IQR 1.7-2.4) and median AMVL midpoint thickness 2.0 mm (IQR 1.7-2.4). The
median aortic valve thickness was 1.5 mm (IQR 1.3-1.6) in the PSLA view and 1.4
mm (IQR 1.2-1.6) in the PSSA view. The interclass correlation coefficient for the
AMVL tip was 0.85 (0.71 to 0.92) and for the AMVL midpoint was 0.77 (0.54 to
0.87). CONCLUSIONS: We have described a standardised method for mitral and aortic
valve measurement in children which is objective and reproducible. Normal ranges
of left heart valve thickness in a high prevalence RHD population are
established. These results provide a reference range for school-age children in
high prevalence RHD regions undergoing echocardiographic screening.
PMID- 28405229
TI - Epidemiologic burden of hospitalisation for congestive heart failure among adults
aged >=19 years in the Philippines.
AB - OBJECTIVES: The study determined the prevalence of hospitalisation due to
congestive heart failure (CHF) among adult patients aged 19 years and above in
the Philippines and its 17 regions in 2014. It also determined the demographic
profile of these patients, aetiology and type of CHF, comorbidities, duration of
hospitalisation and the overall in-hospital mortality rate. METHODS: Data
collection was done using the hospitalisation claims database of the Philippine
Health Insurance Corporation (PhilHealth). All patient claims for CHF, that is,
patients who were admitted from 1 January to 31 December 2014, were included.
Descriptive statistics were utilised to obtain the results. RESULTS: The
prevalence rate was 1.6% or 1648 cases of CHF for every 100 000 patient claims
for medical conditions in 2014. The mean age was 52.6+/-15.1 years. There was no
sex predilection. Only 22.67% of the hospitalisation claims for CHF listed
possible specific aetiologies, the most common of which was hypertensive heart
disease (86.7%). There were more cases of systolic compared to diastolic heart
failure. The mean length of hospital stay was 5.9 days (+8.2) days (median 4
days), with an overall in-hospital mortality rate of 8.2%. CONCLUSIONS: There
were 16 cases of heart failure for every 1000 Filipino patients admitted due to a
medical condition in 2014. Hypertension was possibly the most common aetiologic
factor. Compared to western and Asia-Pacific countries, the local mortality rate
was relatively higher.
PMID- 28405230
TI - LoRTE: Detecting transposon-induced genomic variants using low coverage PacBio
long read sequences.
AB - BACKGROUND: Population genomic analysis of transposable elements has greatly
benefited from recent advances of sequencing technologies. However, the short
size of the reads and the propensity of transposable elements to nest in highly
repeated regions of genomes limits the efficiency of bioinformatic tools when
Illumina or 454 technologies are used. Fortunately, long read sequencing
technologies generating read length that may span the entire length of full
transposons are now available. However, existing TE population genomic softwares
were not designed to handle long reads and the development of new dedicated tools
is needed. RESULTS: LoRTE is the first tool able to use PacBio long read
sequences to identify transposon deletions and insertions between a reference
genome and genomes of different strains or populations. Tested against simulated
and genuine Drosophila melanogaster PacBio datasets, LoRTE appears to be a
reliable and broadly applicable tool to study the dynamic and evolutionary impact
of transposable elements using low coverage, long read sequences. CONCLUSIONS:
LoRTE is an efficient and accurate tool to identify structural genomic variants
caused by TE insertion or deletion. LoRTE is available for download at
http://www.egce.cnrs-gif.fr/?p=6422.
PMID- 28405227
TI - Impact of menopause and diabetes on atherogenic lipid profile: is it worth to
analyse lipoprotein subfractions to assess cardiovascular risk in women?
AB - Cardiovascular disease is the leading cause of death in women at advanced age,
who are affected a decade later compared to men. Cardiovascular risk factors in
women are not properly investigated nor treated and events are frequently lethal.
Both menopause and type 2 diabetes substantially increase cardiovascular risk in
the female sex, promoting modifications on lipid metabolism and circulating
lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a
more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels
of both total high density lipoprotein (HDL) and its subfraction HDL2, but also
higher levels of HDL3 and small low-density lipoprotein particles. This review
discusses the impact of diabetes and menopause to the lipid profile, challenges
in lipoprotein subfractions determination and their potential contribution to the
cardiovascular risk assessment in women. It is still unclear whether lipoprotein
subfraction changes are a major driver of cardiometabolic risk and which
modifications are predominant. Prospective trials with larger samples,
methodological standardizations and pharmacological approaches are needed to
clarify the role of lipoprotein subfractions determination on cardiovascular risk
prediction and intervention planning in postmenopausal women, with or without DM.
PMID- 28405231
TI - Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium
longicirrum, (Gastropoda, Heterobranchia, Nudibranchia).
AB - Phyllodesmium longicirrum is the largest aeolidoidean species known to date, and
extremely rich in terpenoid chemistry. Herein we report the isolation of a total
of 19 secondary metabolites from a single specimen of this species, i.e.,
steroids 1-4, cembranoid diterpenes 5-13, complex biscembranoids 14 and 15, and
the chatancin-type diterpenes 16-19. These compounds resemble those from soft
corals of the genus Sarcophyton, of which to date, however, only S.
trocheliophorum is described as a food source for P. longicirrum. Fish feeding
deterrent activity was determined using the tropical puffer fish Canthigaster
solandri, and showed activity for (2S)-isosarcophytoxide (10), cembranoid
bisepoxide 12 and 4-oxochatancin (16). Determining the metabolome of P.
longicirrum and its bioactivity, makes it evident that this seemingly vulnerable
soft bodied animal is well protected from fish by its chemical arsenal.
PMID- 28405232
TI - Contribution of microreactor technology and flow chemistry to the development of
green and sustainable synthesis.
AB - Microreactor technology and flow chemistry could play an important role in the
development of green and sustainable synthetic processes. In this review, some
recent relevant examples in the field of flash chemistry, catalysis, hazardous
chemistry and continuous flow processing are described. Selected examples
highlight the role that flow chemistry could play in the near future for a
sustainable development.
PMID- 28405234
TI - Effect of the ortho-hydroxy group of salicylaldehyde in the A3 coupling reaction:
A metal-catalyst-free synthesis of propargylamine.
AB - The synthesis of propargylamines via A3 coupling mostly under metal-catalyzed
procedures is well known. This work invented an unprecedented effect of
salicylaldehyde, one of the A3 coupling partners, which could lead to the
formation of propargylamine, an important pharmaceutical building block, in the
absence of any metal catalyst and under mild conditions. The role of the hydroxy
group in ortho position of salicylaldehyde has been explored, which presumably
activates the Csp-H bond of the terminal alkyne leading to the formation of
propargylamines in good to excellent yields, thus negating the function of the
metal catalyst. This observation is hitherto unknown, tested for a variety of
salicylaldehyde, amine and acetylene, established as a general protocol, and is
believed to be of interest for synthetic chemists from green chemistry.
PMID- 28405233
TI - Novel beta-cyclodextrin-eosin conjugates.
AB - Eosin B (EoB) and eosin Y (EoY), two xanthene dye derivatives with
photosensitizing ability were prepared in high purity through an improved
synthetic route. The dyes were grafted to a 6-monoamino-beta-cyclodextrin
scaffold under mild reaction conditions through a stable amide linkage using the
coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium
chloride. The molecular conjugates, well soluble in aqueous medium, were
extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry.
Preliminary spectroscopic investigations showed that the beta-cyclodextrin-EoY
conjugate retains both the fluorescence properties and the capability to
photogenerate singlet oxygen of the unbound chromophore. In contrast, the
corresponding beta-cyclodextrin-EoB conjugate did not show either relevant
emission or photosensitizing activity probably due to aggregation in aqueous
medium, which precludes any response to light excitation.
PMID- 28405235
TI - Fast and efficient synthesis of microporous polymer nanomembranes via light
induced click reaction.
AB - Conjugated microporous polymers (CMPs) are materials of low density and high
intrinsic porosity. This is due to the use of rigid building blocks consisting
only of lightweight elements. These materials are usually stable up to
temperatures of 400 degrees C and are chemically inert, since the networks are
highly crosslinked via strong covalent bonds, making them ideal candidates for
demanding applications in hostile environments. However, the high stability and
chemical inertness pose problems in the processing of the CMP materials and their
integration in functional devices. Especially the application of these materials
for membrane separation has been limited due to their insoluble nature when
synthesized as bulk material. To make full use of the beneficial properties of
CMPs for membrane applications, their synthesis and functionalization on surfaces
become increasingly important. In this respect, we recently introduced the solid
liquid interfacial layer-by-layer (LbL) synthesis of CMP-nanomembranes via Cu
catalyzed azide-alkyne cycloaddition (CuAAC). However, this process featured very
long reaction times and limited scalability. Herein we present the synthesis of
surface grown CMP thin films and nanomembranes via light induced thiol-yne click
reaction. Using this reaction, we could greatly enhance the CMP nanomembrane
synthesis and further broaden the variability of the LbL approach.
PMID- 28405236
TI - Pd- and Cu-catalyzed approaches in the syntheses of new cholane
aminoanthraquinone pincer-like ligands.
AB - Cu- and Pd-catalyzed arylation of aminocholanes has been described for the first
time. While this Cu-catalyzed protocol provides high yields in reactions of
aminocholanes with iodoarenes, Pd catalysis was found to be preferable for the
reactions of aminocholanes with dichloroanthraquinones. UV-vis titration of
bis(cholanylamino)anthraquinones with a series of cations demonstrated their high
binding affinity to Cu2+, Al3+, and Cr3+.
PMID- 28405237
TI - Studies directed toward the exploitation of vicinal diols in the synthesis of (+)
nebivolol intermediates.
AB - While the exploitation of the Sharpless asymmetric dihydroxylation as the source
of chirality in the synthesis of acyclic molecules and saturated heterocycles has
been tremendous, its synthetic utility toward chiral benzo-annulated heterocycles
is relatively limited. Thus, in the search for wider applications of Sharpless
asymmetric dihydroxylation-derived diols for the synthesis of benzo-annulated
heterocycles, we report herein our studies in the asymmetric synthesis of (R)-1
((R)-6-fluorochroman-2-yl)ethane-1,2-diol, (R)-1-((S)-6-fluorochroman-2-yl)ethane
1,2-diol and (S)-6-fluoro-2-((R)-oxiran-2-yl)chroman, which have been used as
late-stage intermediates for the asymmetric synthesis of the antihypertensive
drug (S,R,R,R)-nebivolol. Noteworthy is that a large number of racemic and
asymmetric syntheses of nebivolol and their intermediates have been described in
the literature, however, the Sharpless asymmetric dihydroxylation has never been
employed as the sole source of chirality for this purpose.
PMID- 28405238
TI - Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines
leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3
aminides.
AB - Depending on the reaction conditions, N,N',N''-tris(benzylamino)guanidinium salts
can react with carboxylic acid chlorides to form either symmetrical N,N',N''
tris(N-acyl-N-benzylamido)guanidines 6 or mesoionic 4-amino-1,2,4-triazolium-3
hydrazinides 7. The latter were converted into 1,2,4-triazolium salts by
protonation or methylation at the hydrazinide nitrogen atom. Neutral 1,2,4
triazoles 10 were obtained by catalytic hydrogenation of an N-benzyl derivative.
Crystal structure analyses of a 4-benzylamino-1,2,4-triazolium-3-hydrazinide and
of two derived 1,2,4-triazolium salts are presented.
PMID- 28405239
TI - Transition-metal-catalyzed synthesis of phenols and aryl thiols.
AB - Phenols and aryl thiols are fundamental building blocks in organic synthesis and
final products with interesting biological activities. Over the past decades,
substantial progress has been made in transition-metal-catalyzed coupling
reactions, which resulted in the emergence of new methods for the synthesis of
phenols and aryl thiols. Aryl halides have been extensively studied as substrates
for the synthesis of phenols and aryl thiols. In very recent years, C-H
activation represents a powerful strategy for the construction of functionalized
phenols directly from various arenes. However, the synthesis of aryl thiols
through C-H activation has not been reported. In this review, a brief overview is
given of the recent advances in synthetic strategies for both phenols and aryl
thiols.
PMID- 28405242
TI - JOCB Bulletin.
PMID- 28405240
TI - Targeting the ubiquitin-conjugating enzyme E2D4 for cancer drug discovery-a
structure-based approach.
AB - Cancer progression is a global burden. The incidence and mortality now reach 30
million deaths per year. Several pathways of cancer are under investigation for
the discovery of effective therapeutics. The present study highlights the
structural details of the ubiquitin protein 'Ubiquitin-conjugating enzyme E2D4'
(UBE2D4) for the novel lead structure identification in cancer drug discovery
process. The evaluation of 3D structure of UBE2D4 was carried out using homology
modelling techniques. The optimized structure was validated by standard
computational protocols. The active site region of the UBE2D4 was identified
using computational tools like CASTp, Q-site Finder and SiteMap. The hydrophobic
pocket which is responsible for binding with its natural receptor ubiquitin
ligase CHIP (C-terminal of Hsp 70 interacting protein) was identified through
protein-protein docking study. Corroborating the results obtained from active
site prediction tools and protein-protein docking study, the domain of UBE2D4
which is responsible for cancer cell progression is sorted out for further
docking study. Virtual screening with large structural database like CB_Div Set
and Asinex BioDesign small molecular structural database was carried out. The
obtained new ligand molecules that have shown affinity towards UBE2D4 were
considered for ADME prediction studies. The identified new ligand molecules with
acceptable parameters of docking, ADME are considered as potent UBE2D4 enzyme
inhibitors for cancer therapy.
PMID- 28405241
TI - Design and synthesis of a new steroid-macrocyclic derivative with biological
activity.
AB - The aims of this study were to evaluate the positive inotropic effect of a new
macrocyclic derivative (compound 11) and characterize the molecular mechanism
involved in its biological activity. The first step was achieved by synthesis of
a macrocyclic derivative involving a series of reactions for the preparation of
several steroid derivatives such as (a) steroid-pyrimidinone (3 and 4), (b)
steroid-amino (5), (c) steroid-imino (6), (d) ester-steroid (7 and 8), and (e)
amido-steroid (9 and 10). Finally, 11 was prepared by removing the tert
butyldimethylsilane fragment of 10. The biological activity of compounds on
perfusion pressure and vascular resistance was evaluated on isolated rat heart
using the Langendorff model. The inotropic activity of 11 was evaluated in
presence of prazosin, metoprolol, indomethacin, nifedipine, and flutamide to
characterize its molecular mechanism. Theoretical experiments were carried out
with a Docking model, to assess potential interactions of androgen receptor with
11. The results showed that only this macrocyclic derivative exerts changes on
perfusion pressure and vascular resistance translated as the positive inotropic
effect, and this effect was blocked with flutamide; these data indicate that the
positive inotropic activity induced by this macrocyclic derivative was via
androgen receptor activation. The theoretical results indicated that the
interaction of the macrocyclic derivative with the androgen receptor involves
several amino acid residues such as Leu704, Asn705, Met780, Cys784, Met749,
Leu762, Phe764, Ser778, and Met787. In conclusion, all these data suggest that
the positive inotropic activity of the macrocyclic derivative may depend on its
chemical structure.
PMID- 28405243
TI - Transcriptomic responses of the liver and adipose tissues to altered carbohydrate
fat ratio in diet: an isoenergetic study in young rats.
AB - BACKGROUND: To elucidate the effects of altered dietary carbohydrate and fat
balance on liver and adipose tissue transcriptomes, 3-week-old rats were fed
three kinds of diets: low-, moderate-, and high-fat diets (L, M, and H)
containing a different ratio of carbohydrate-fat (C-F) (65:15, 60:20, and 35:45
in energy percent, respectively). METHODS: The rats consumed the diets for 9
weeks and were subjected to biochemical and DNA microarray analyses. RESULTS: The
rats in the H-group exhibited lower serum triacylglycerol (TG) levels but higher
liver TG and cholesterol content than rats in the L-group. The analysis of
differentially expressed genes (DEGs) between each group (L vs M, M vs H, and L
vs H) in the liver revealed about 35% of L vs H DEGs that were regulated in the
same way as M vs H DEGs, and most of the others were L- vs H-specific. Gene
ontology analysis of these L vs H DEGs indicated that those related to fatty acid
synthesis and circadian rhythm were enriched. Interestingly, about 30% of L vs M
DEGs were regulated in a reverse way compared with L vs H and M vs H DEGs. These
reversed liver DEGs included M-up/H-down genes (Sds for gluconeogenesis from
amino acids) and M-down/H-up genes (Gpd2 for gluconeogenesis from glycerol,
Agpat9 for TG synthesis, and Acot1 for beta-oxidation). We also analyzed L vs H
DEGs in white (WAT) and brown (BAT) adipose tissues and found that both oxidation
and synthesis of fatty acids were inhibited in these tissues. CONCLUSIONS: These
results indicate that the alteration of dietary C-F balance differentially
affects the transcriptomes of metabolizing and energy-storing tissues.
PMID- 28405245
TI - Chemical Composition and Microhardness of Human Enamel Treated with Fluoridated
Whintening Agents. A Study in Situ.
AB - BACKGROUND: Dental whitening has been increasingly sought out to improve dental
aesthetics, but may cause chemical and morphological changes in dental enamel
surfaces. OBJECTIVE: Assess in situ the effects of high-concentration hydrogen
peroxide with and without fluoride on human dental enamel using the ion
chromatography test (IC) and the Knoop hardness test (KHN). MATERIAL AND METHODS:
Nineteen enamel specimens were prepared using third human molars. These specimens
were fixed on molars of volunteers and were divided into groups: OP38-Opalescence
Boost PF38%, PO37-Pola Office 37.5% and CO-Control group. For chemical analysis
(n= 3), the dentin layer was removed, keeping only the enamel, which was
subjected to acidic digestion by microwave radiation. It was necessary to perform
sample dilutions for the elements fluorine (F), calcium (Ca) and phosphorus (P)
for quantification using the IC test. The KHN (n= 5) was performed before and
after the treatments. Five indentations were made, separated by 100 um, for each
specimen using a load of 25 gf for 5 seconds in the microdurometer. The data were
analyzed using ANOVA with a 5% significance level. RESULTS: The OP38 group had
the largest concentrations of F, Ca and P ions. The PO37 group showed the lowest
concentrations of F and Ca ions. The average KHN was not significantly different
between the OP38 and PO37 groups. CONCLUSION: Enamel whitened with hydrogen
peroxide containing fluoride had greater concentrations of F, Ca and P ions. The
presence of fluoride in the whitening agent did not influence the enamel
microhardness.
PMID- 28405244
TI - Clusterization in head and neck squamous carcinomas based on lncRNA expression:
molecular and clinical correlates.
AB - BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as key players in a
remarkably variety of biological processes and pathologic conditions, including
cancer. Next-generation sequencing technologies and bioinformatics procedures
predict the existence of tens of thousands of lncRNAs, from which we know the
functions of only a handful of them, and very little is known in cancer types
such as head and neck squamous cell carcinomas (HNSCCs). RESULTS: Here, we use
RNAseq expression data from The Cancer Genome Atlas (TCGA) and various statistic
and software tools in order to get insight about the lncRNome in HNSCC. Based on
lncRNA expression across 426 samples, we discover five distinct tumor clusters
that we compare with reported clusters based on various genomic/genetic features.
Results demonstrate significant associations between lncRNA-based clustering and
DNA methylation, TP53 mutation, and human papillomavirus infection. Using "guilt
by-association" procedures, we infer the possible biological functions of
representative lncRNAs of each cluster. Furthermore, we found that lncRNA
clustering is correlated with some important clinical and pathologic features,
including patient survival after treatment, tumor grade, or sub-anatomical
location. CONCLUSIONS: We present a landscape of lncRNAs in HNSCC and provide
associations with important genotypic and phenotypic features that may help to
understand the disease.
PMID- 28405247
TI - The misrepresentation of high drug costs: Who is looking out for the patient?
PMID- 28405246
TI - Modulation of benzo[a]pyrene-DNA adduct formation by CYP1 inducer and inhibitor.
AB - Benzo[a]pyrene (BaP) is a well-studied pro-carcinogen that is metabolically
activated by cytochrome P450 enzymes. Cytochrome P4501A1 (CYP1A1) has been
considered to play a central role in the activation step, which is essential for
the formation of DNA adducts. This enzyme is strongly induced by many different
chemical agents, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which
binds to the aryl hydrocarbon receptor (AhR). Therefore, AhR activators are
suspected to have the potential to aggravate the toxicity of BaP through the
induction of CYP1A1. Besides, CYP1A1 inhibitors, including its substrates, are
estimated to have preventive effects against BaP toxicity. However, strangely,
increased hepatic BaP-DNA adduct levels have been reported in Cyp1a1 knockout
mice. Moreover, numerous reports describe that concomitant treatment of AhR
activators reduced BaP-DNA adduct formation. In an experiment using several human
cell lines, TCDD had diverse modulatory effects on BaP-DNA adducts, both
enhancing and inhibiting their formation. In this review, we focus on the factors
that could influence the BaP-DNA adduct formation. To interpret these complicated
outcomes, we propose a hypothesis that CYP1A1 is a key enzyme for both generation
and reduction of (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), the
major carcinogenic intermediate of BaP. Conversely, CYP1B1 is thought to
contribute only to the metabolic activation of BaP related to carcinogenesis.
PMID- 28405248
TI - ?
PMID- 28405249
TI - Innovative pharmacy practice: Chloe McMillan.
PMID- 28405250
TI - The management of venous thromboembolism: A practical tool for the front-line
clinician.
PMID- 28405251
TI - Applying the pharmaceutical care model to assess pharmacist services in a primary
care setting.
PMID- 28405252
TI - Patient engagement in pharmacy practice research.
PMID- 28405253
TI - Keeping up with the evidence: Resources used by a busy pharmacist.
PMID- 28405254
TI - Risk of falls associated with antiepileptic drug use in ambulatory elderly
populations: A systematic review.
AB - BACKGROUND: Falls are a major cause of morbidity and mortality in older adults.
About a third of those aged 65 years or older fall at least once each year, which
can result in hospitalizations, hip fractures and nursing home admissions that
incur high costs to individuals, families and society. The objective of this
clinical review was to assess the risk of falls in ambulatory older adults who
take antiepileptic drugs, medications that can increase fall risk and decrease
bone density. METHODS: PubMed, EMBASE, MEDLINE and the Cochrane Library
electronic databases were searched from inception to July 2014. Case-control,
quasi-experimental and observational design studies published in English that
assessed quantifiable fall risk associated with antiepileptic drug use in
ambulatory patient populations with a mean or median age of 65 years or older
were eligible for inclusion. One author screened all titles and abstracts from
the initial search. Two authors independently reviewed and abstracted data from
full-text articles that met eligibility criteria. RESULTS: Searches yielded 399
unique articles, of which 7 met inclusion criteria-4 prospective or longitudinal
cohort studies, 1 cohort study with a nested case-control, 1 cross-sectional
survey and 1 retrospective cross-sectional database analysis. Studies that
calculated the relative risk of falls associated with antiepileptic drug use
reported a range of 1.29 to 1.62. Studies that reported odds ratios of falls
associated with antiepileptic drug use ranged from 1.75 to 6.2 for 1 fall or at
least 1 fall and from 2.56 to 7.1 for more frequent falls. DISCUSSION: Health
care professionals should monitor older adults while they take antiepileptic
drugs to balance the need for such pharmacotherapy against an increased risk of
falling and injuries from falls.
PMID- 28405255
TI - Medication management of chronic pain: A comparison of 2 care delivery models.
AB - BACKGROUND: The prevalence of chronic pain is high and increasing. Medication
management is an important component of chronic pain management. There is a
shortage of physicians who are available and comfortable providing this service.
In Alberta, pharmacists have been granted an advanced scope of practice. Given
this empowerment, their availability, training and skill set, pharmacists are
well positioned to play an expanded role in the medication management of chronic
pain sufferers. OBJECTIVE: To compare the effectiveness and cost of a physician
only vs a pharmacist-physician team model of medication management for chronic
nonmalignant pain sufferers. METHOD: Data was analyzed for 89 patients who had
received exclusively medication management at a rural Alberta multidisciplinary
clinic. 56 were managed by a sole physician. 33 were managed by a team
(pharmacist + physician). In the team model, the physician did the medical
assessment, diagnosis, and established a treatment plan in consultation with the
patient and pharmacist. The pharmacist then provided the ongoing follow-up
including education, dose titration and side effect management and consulted with
the physician as needed. Change in pain (Numerical Rating Scale) and disability
(Pain Interference Questionnaire) over the course of treatment were recorded. The
treatment duration and number of visits were used to calculate cost of care.
RESULTS: Both models of medication management resulted in significant and
comparable improvements in pain, disability and patient perception of medication
effectiveness. Patients in the physician-only group were seen more frequently and
at a greater cost. The pharmacist-physician team approach was markedly more cost
effective, and patients expressed a high level of satisfaction with their
medication management. CONCLUSIONS: The pharmacist-physician team model of
medication management results in significant reductions of pain and disability
for chronic nonmalignant pain sufferers at a reduced cost and is well accepted by
patients.
PMID- 28405256
TI - Dementia: What pharmacists need to know.
PMID- 28405257
TI - A simple remedy for overprecision in judgment.
AB - Overprecision is the most robust type of overconfidence. We present a new method
that significantly reduces this bias and offers insight into its underlying
cause. In three experiments, overprecision was significantly reduced by forcing
participants to consider all possible outcomes of an event. Each participant was
presented with the entire range of possible outcomes divided into intervals, and
estimated each interval's likelihood of including the true answer. The
superiority of this Subjective Probability Interval Estimate (SPIES) method is
robust to range widths and interval grain sizes. Its carryover effects are
observed even in subsequent estimates made using the conventional, 90% confidence
interval method: judges who first made SPIES judgments considered a broader range
of values in subsequent conventional interval estimates as well.
PMID- 28405258
TI - Rapid isolation of blood plasma using a cascaded inertial microfluidic device.
AB - Blood, saliva, mucus, sweat, sputum, and other biological fluids are often
hindered in their ability to be used in point-of-care (POC) diagnostics because
their assays require some form of off-site sample pre-preparation to effectively
separate biomarkers from larger components such as cells. The rapid isolation,
identification, and quantification of proteins and other small molecules
circulating in the blood plasma from larger interfering molecules are therefore
particularly important factors for optical blood diagnostic tests, in particular,
when using optical approaches that incur spectroscopic interference from
hemoglobin-rich red blood cells (RBCs). In this work, a sequential spiral
polydimethylsiloxane (PDMS) microfluidic device for rapid (~1 min) on-chip blood
cell separation is presented. The chip utilizes Dean-force induced migration via
two 5-loop Archimedean spirals in series. The chip was characterized in its
ability to filter solutions containing fluorescent beads and silver nanoparticles
and further using blood solutions doped with a fluorescent protein. Through these
experiments, both cellular and small molecule behaviors in the chip were
assessed. The results exhibit an average RBC separation efficiency of ~99% at a
rate of 5.2 * 106 cells per second while retaining 95% of plasma components. This
chip is uniquely suited for integration within a larger point-of-care diagnostic
system for the testing of blood plasma, and the use of multiple filtering spirals
allows for the tuning of filtering steps, making this device and the underlying
technique applicable for a wide range of separation applications.
PMID- 28405259
TI - A549 and MRC-5 cell aggregation in a microfluidic Lab-on-a-chip system.
AB - In this paper, we present a culture of A549 and MRC-5 spheroids in a microfluidic
system. The aim of our work was to develop a good lung cancer model for the
evaluation of drug cytotoxicity. Our research was focused on determining the
progress of cell aggregation depending on such factors as the depth of culture
microwells in the microdevices, a different flow rate of the introduced cell
suspensions, and the addition of collagen to cell suspensions. We showed that
these factors had a significant influence on spheroid formation. It was found
that both MRC-5 and A549 cells exhibited higher aggregation in 500 MUm
microwells. We also noticed that collagen needs to be added to A549 cells to form
the spheroids. Optimizing the mentioned parameters allowed us to form 3D lung
tissue models in the microfluidic system during the 10-day culture. This study
indicates how important an appropriate selection of the specified parameters is
(e.g., geometry of the microwells in the microsystem) to obtain the spheroids
characterized by high viability in the microfluidic system.
PMID- 28405260
TI - Mindfulness-Based Interventions for Weight Loss and CVD Risk Management.
AB - Obesity affects more than one-third of U.S. adults and is a major cause of
preventable morbidity and mortality, primarily from cardiovascular disease.
Traditional behavioral interventions for weight loss typically focus on diet and
exercise habits and often give little attention to the role of stress and
emotions in the initiation and maintenance of unhealthy behaviors, which may
account for their modest results and considerable variability in outcomes. Stress
eating and emotional eating are increasingly recognized as important targets of
weight loss interventions. Mindfulness-based interventions were specifically
developed to promote greater self-efficacy in coping with stress and negative
emotions, and appear to be effective for a variety of conditions. In recent years
researchers have begun to study mindfulness interventions for weight loss and CVD
risk management. This review describes the rationale for the use of mindfulness
in interventions for weight loss and CVD risk management, summarizes the research
to date, and suggests priorities for future research.
PMID- 28405261
TI - Blocking of the Lymphatic Vessel in Lymphedema.
AB - Objective: In this case report, we present a case wherein we observed a blocking
of lymphatic vessels in indocyanine green lymphography and found a shrunken
lymphatic vessel intraoperatively. Methods: We performed indocyanine green
lymphography and lymphaticovenous anastomosis on a 77-year-old woman. She had
previously undergone right mastectomy and axillary lymph node dissection
accompanied by radiotherapy and chemotherapy for right breast cancer. She noticed
swelling in the right upper limb 22 years after the surgery and consulted our
hospital. Although she started wearing elastic sleeve, there was still stiffness
in the right upper limb, and we decided to perform lymphaticovenous anastomosis 5
months after the first consultation. Results: In the preoperative indocyanine
green lymphography, we observed a linear pattern in the medial side of the right
forearm, which suddenly blocked in the middle of the forearm. At that point, we
observed dilated lymphatic vessels that were suddenly shrunken at the proximal
side intraoperatively. We performed lymphaticovenous anastomosis with the dilated
part of this lymphatic vessel. We also performed 4 additional lymphaticovenous
anastomoses. The operation time was 2 hours 10 minutes, and the amount of
bleeding was minimal. The right upper limb of the patient got softer, and she was
satisfied with the result 3 months after the operation. The average circumference
change at the 5 points in the right upper limb was -1.26 cm (range, -2.3 to -0.3
cm). Conclusions: There was a possibility that the blocking of the lymphatic
vessels was a cause of lymphedema in the upper extremity.
PMID- 28405262
TI - A Psychosocial Analysis of the Effect of Body-Contouring Surgery on Patients
After Weight Loss.
AB - Objectives (Background): Patients are often bothered by excess skin laxity and
redundancy after weight loss. Body-contouring surgery offers a solution. This
study assessed the psychosocial impact of body-contouring surgery on patients
after weight loss. Methods (Settings, Design): In this cross-sectional study, a
specifically designed questionnaire developed in collaboration with psychiatric
department for our research was used for 43 patients who underwent body
contouring surgery. Data were collected during single visit to the plastic
surgery clinic. All the patients had lost 20 kg or less before the surgery and
were interviewed at least 6 months after the surgery. The questionnaire was used
to compare the psychosocial status of the patients before and after surgery. Data
were analyzed appropriately using Statistical Package for the Social Sciences.
Results: The participants' mean age was 34 +/- 10 years; the sample included 24
(55.8%) women and 19 (44.2%) men (total N = 43). The patients' quality of life
improved significantly in the areas of social life (P < .001), job performance (P
< .002), and sexual activity (P < .001). Moreover, while 17 (39.5%) patients
suffered symptoms of depression before surgery, only 1 (2.3%) patient suffered
symptoms of depression after surgery. The overall satisfaction was found to be
62.8%, with mammoplasty being the procedure with the highest satisfaction
(66.6%). Conclusion: Body-contouring surgery after weight loss has shown to
improve both psychological and social aspects of the patients' lives. Recall bias
is the main limitation in our study.
PMID- 28405263
TI - Direct-Contact Low-Frequency Ultrasound Clearance of Biofilm From Metallic
Implant Materials.
AB - Introduction: Biofilms are recognized as a significant deterrent to wound healing
and to the management of exposed or infected surgical implants. Biofilms can be
disrupted by a variety of enzymatic and mechanical interventions. This experiment
was designed to determine whether direct-contact low-frequency ultrasound has the
ability to clear biofilms and what then happens to the released bacteria.
Methods:Staphylococcus epidermidis biofilm was grown on the surfaces of metallic
discs composed of titanium and stainless steel, comparable with the alloys used
in surgical implants. The discs were treated with a control of irrigation and no
ultrasound, followed by the ultrasound for a 10 second of exposure at a mid-level
power setting. The irrigation materials used was either normal saline or
hypochlorous acid. The effluent was cultured to determine colony-forming units,
and the discs were stained with crystal violet to determine whether there was a
residual biofilm. Results: The biofilm was cleared completely from all discs when
treated with direct-contact low-frequency ultrasound. However, the released
bacteria were viable and could be cultured from the effluent when saline was used
as the irrigation medium. When hypochlorous acid was used as the irrigation
medium, there was complete killing of all planktonic bacteria. Conclusion: Direct
contact low-frequency ultrasound is effective when used to clear biofilms from
metallic implant materials. By using hypochlorous acid as the irrigant during
treatment, all of the bacteria released from the biofilm were killed as well. The
implications for clinical application are important and need to be independently
studied.
PMID- 28405264
TI - BLT2 expression improves skin integrity and protects from alterations caused by
hyperglycemia in type 2 diabetes.
AB - Type 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where
chronic high blood sugar produces complications such as delayed wound healing.
Reports have shown that BLT2 activation improves keratinocyte migration and wound
healing, as well as protecting the epidermal barrier through the promotion of
actin polymerization. The goal of this study was to elucidate the role of BLT2
expression in skin epithelial integrity in T2D. For this purpose, we used both
wild type (WT) and BLT2 knockout mice in a model, in which a T2D-like phenotype
was induced by keeping the animals on a high fat (HF) diet over 5 weeks. In a
parallel in vitro approach, we cultured BLT2-transfected HaCaT cells at both low
and high glucose concentrations for 48 h. Structure, transepithelial resistance
(TEER), IL-1beta, IL-8 or CXCL2, MMP9, Filaggrin, Loricrin and Keratin 10 (K10)
were evaluated ex vivo and in vitro. Additionally, wound healing (WH) was studied
in vitro. The skin from T2D and BLT2 knockout mice showed a reduction in TEER and
the expression of IL-1beta, and in increase in CXCL2, MMP9, Filaggrin, Loricrin
and K10 expression. The structure suggested an atrophic epidermis; however, the
skin was dramatically affected in the BLT2 knockout mice kept on a HF diet. HaCaT
BLT2 cells presented as an organized monolayer and showed higher TEER and wound
healing compared with vector only-transfected HaCaT-Mock cells. Likewise,
alterations in the expression of skin inflammatory, matrix degradation and
differentiation markers under low and high glucose conditions were less severe
than in HaCaT-Mock cells. Our results suggest that BLT2 improves epithelial
integrity and function by regulating differentiation markers, cytokines and MMP9.
Furthermore, BLT2 attenuates the damaging effects of high glucose levels, thereby
accelerating wound healing.
PMID- 28405265
TI - Socio-epidemiologic aspects and cutaneous side effects of permanent tattoos in
Germany - Tattoos are not restricted to a specific social phenotype.
AB - Background: More and more people of all age classes have a tattoo. Intriguingly,
there are multiple prejudices in the general population and published data that
concern tattooed persons, such as being criminals, having a low education, being
alcohol or drug abusers, or more risky in their life style. Objective: To obtain
and to evaluate sociodemographic data on tattooed persons, to investigate the
incidence of tattoo-related cutaneous complications and to define personal risk
factors and course of the persons after being tattooed concerning behavior of
personal environment. Patients and Methods: We interviewed 426 participants with
already existing tattoos and 20 participants just before getting a new tattoo by
using an online questionnaire. The participators were asked about socio
epidemiologic aspects of tattoos in general and special aspects of their own
tattoo(s) in particular. There were no exclusion criteria. Results: Tattoos are
interesting for people seeking popular body art, esp. university graduates and
financially-secure individuals. 446 persons participated in this study. Most of
the persons were female with a mean age of 35. Local pruritus around the tattooed
area was the most common cutaneous side effect among the participants. 93.5% of
the participants did not want a tattoo removal. Intriguingly, most of the
participants experienced no career problems related to the tattoo(s).
Limitations: The study population is not representative as we included only
persons being tattooed prior to or getting newly tattooed. Furthermore, there is
a potential selection bias as the participation in this study was voluntary. Only
persons that felt involved by the flyer did answer the questionnaire. Conclusion:
The present data shows that common tattooed persons are not low educated
criminals with any drug or alcohol abuse or with risky life style. Nowadays being
tattooed encompasses a kind of body art and displays a certain kind of lifestyle
habit.
PMID- 28405266
TI - Commercial tanning salons and melanoma risk.
AB - There have been many case-control studies of melanoma and the use of indoor
tanning equipment. A recent meta analysis of 8 credible studies in North America
estimated an overall significant odds ratio of 1.23. Three of these 8 studies
also reported separately on commercial use and home use of indoor tanning
equipment. For home use the overall odds ratio was a significant 1.53 while for
commercial use there was a non significant 1.05.
PMID- 28405267
TI - Reversing the rewiring of cancer.
PMID- 28405268
TI - Revisiting the phylogeny of Wolbachia in Collembola.
AB - The endosymbiont Wolbachia has been detected in a few parthenogenetic
collembolans sampled in Europe and America, including three species of
Poduromorpha, two species of Entomobryomorpha, and two species of Neelipleona.
Based on 16S rRNA and ftsZ gene sequences, most of the Wolbachia infecting
parthenogenetic collembolans were characterized as members of supergroup E and
showed concordant phylogeny with their hosts. However, the two neelipleonan
symbionts form another unique group, indicating that Wolbachia has infected
parthenogenetic collembolans multiple times. In this study, five parthenogenetic
collembolan species were identified as hosts of Wolbachia, and four new Wolbachia
strains were reported for four collembolan species sampled in China,
respectively, including a neelipleonan strain from Megalothorax incertus (wMinc).
Our results demonstrated that the Wolbachia multilocus sequence typing (MLST)
system is superior to the 16S rRNA + ftsZ approach for phylogenetic analyses of
collembolan Wolbachia. The MLST system assigned these Wolbachia of
parthenogenetic collembolans to supergroup E as a unique clade, which included
wMinc, supporting the monophyletic origin of Wolbachia in parthenogenetic
collembolan species. Moreover, our data suggested supergroup E as one of the most
divergent lineages in Wolbachia and revealed the discrepancy between the
phylogenies of Wolbachia from parthenogenetic collembolans and their hosts, which
may result from the high level of genetic divergence between collembolan
Wolbachia, in association with the geographic differentiation of their hosts, or
the possible horizontal transmission of Wolbachia between different collembolan
species.
PMID- 28405269
TI - The trade-off between fecundity and egg size in a polymorphic population of
Arctic charr (Salvelinus alpinus (L.)) in Skogsfjordvatn, subarctic Norway.
AB - Reproductive traits differ between intralacustrine Arctic charr morphs. Here, we
examine three sympatric lacustrine Arctic charr morphs with respect to fecundity,
egg size and spawning time/site to assess reproductive investments and trade
offs, and possible fitness consequences. The littoral omnivore morph (LO-morph)
utilizes the upper water for feeding and reproduction and spawn early in October.
The large profundal piscivore morph (PP-morph) and the small profundal benthivore
morph (PB-morph) utilize the profundal habitat for feeding and reproduction and
spawn in December and November, respectively. Females from all morphs were
sampled for fecundity and egg-size analysis. There were large differences between
the morphs. The PB-morph had the lowest fecundity (mean = 45, SD = 13) and
smallest egg size (mean = 3.2 mm, SD = 0.32 mm). In contrast, the PP-morph had
the highest fecundity (mean = 859.5, SD = 462) and the largest egg size (mean =
4.5 mm, SD = 0.46 mm), whereas the LO-morph had intermediate fecundity (mean =
580, SD = 225) and egg size (mean = 4.3, SD = 0.24 mm). Fecundity increased with
increasing body size within each morph. This was not the case for egg size, which
was independent of body sizes within morph. Different adaptations to feeding and
habitat utilization have apparently led to a difference in the trade-off between
fecundity and egg size among the three different morphs.
PMID- 28405270
TI - Group foraging in Socotra cormorants: A biologging approach to the study of a
complex behavior.
AB - Group foraging contradicts classic ecological theory because intraspecific
competition normally increases with aggregation. Hence, there should be
evolutionary benefits to group foraging. The study of group foraging in the field
remains challenging however, because of the large number of individuals involved
and the remoteness of the interactions to the observer. Biologging represents a
cost-effective solution to these methodological issues. By deploying GPS and
temperature-depth loggers on individuals over a period of several consecutive
days, we investigated intraspecific foraging interactions in the Socotra
cormorant Phalacrocorax nigrogularis, a threatened colonial seabird endemic to
the Arabian Peninsula. In particular, we examined how closely birds from the same
colony associated with each other spatially when they were at sea at the same
time and the distance between foraging dives at different periods of the day.
Results show that the position of different birds overlapped substantially, all
birds targeting the same general foraging grounds throughout the day, likely
following the same school of fish. There were as many as 44,500 birds within the
foraging flock at sea at any time (50% of the colony), and flocking density was
high, with distance between birds ranging from 8 to 1,380 m. Birds adopted a
diving strategy maximizing time spent underwater relative to surface time,
resulting in up to 72% of birds underwater in potential contact with prey at all
times while foraging. Our data suggest that the benefits of group foraging
outweigh the costs of intense aggregation in this seabird. Prey detection and
information transmission are facilitated in large groups. Once discovered,
shoaling prey are concentrated under the effect of the multitude. Fish school
cohesiveness is then disorganized by continuous attacks of diving birds to
facilitate prey capture. Decreasing population size could pose a risk to the
persistence of threatened seabirds where group size is important for foraging
success.
PMID- 28405271
TI - Resemblance profiles as clustering decision criteria: Estimating statistical
power, error, and correspondence for a hypothesis test for multivariate
structure.
AB - Clustering data continues to be a highly active area of data analysis, and
resemblance profiles are being incorporated into ecological methodologies as a
hypothesis testing-based approach to clustering multivariate data. However, these
new clustering techniques have not been rigorously tested to determine the
performance variability based on the algorithm's assumptions or any underlying
data structures. Here, we use simulation studies to estimate the statistical
error rates for the hypothesis test for multivariate structure based on
dissimilarity profiles (DISPROF). We concurrently tested a widely used algorithm
that employs the unweighted pair group method with arithmetic mean (UPGMA) to
estimate the proficiency of clustering with DISPROF as a decision criterion. We
simulated unstructured multivariate data from different probability distributions
with increasing numbers of objects and descriptors, and grouped data with
increasing overlap, overdispersion for ecological data, and correlation among
descriptors within groups. Using simulated data, we measured the resolution and
correspondence of clustering solutions achieved by DISPROF with UPGMA against the
reference grouping partitions used to simulate the structured test datasets. Our
results highlight the dynamic interactions between dataset dimensionality, group
overlap, and the properties of the descriptors within a group (i.e.,
overdispersion or correlation structure) that are relevant to resemblance
profiles as a clustering criterion for multivariate data. These methods are
particularly useful for multivariate ecological datasets that benefit from
distance-based statistical analyses. We propose guidelines for using DISPROF as a
clustering decision tool that will help future users avoid potential pitfalls
during the application of methods and the interpretation of results.
PMID- 28405272
TI - Prey diversity as a driver of resource partitioning between river-dwelling fish
species.
AB - Although food resource partitioning among sympatric species has often been
explored in riverine systems, the potential influence of prey diversity on
resource partitioning is little known. Using empirical data, we modeled food
resource partitioning (assessed as dietary overlap) of coexisting juvenile
Atlantic salmon (Salmo salar) and alpine bullhead (Cottus poecilopus).
Explanatory variables incorporated into the model were fish abundance, benthic
prey diversity and abundance, and several dietary metrics to give a total of
seventeen potential explanatory variables. First, a forward stepwise procedure
based on the Akaike information criterion was used to select explanatory
variables with significant effects on food resource partitioning. Then, linear
mixed-effect models were constructed using the selected explanatory variables and
with sampling site as a random factor. Food resource partitioning between salmon
and bullhead increased significantly with increasing prey diversity, and the
variation in food resource partitioning was best described by the model that
included prey diversity as the only explanatory variable. This study provides
empirical support for the notion that prey diversity is a key driver of resource
partitioning among competing species.
PMID- 28405273
TI - Assortative mating by colored ornaments in blue tits: space and time matter.
AB - Assortative mating is a potential outcome of sexual selection, and estimating its
level is important to better understand local adaptation and underlying trait
evolution. However, assortative mating studies frequently base their conclusions
on small numbers of individuals sampled over short periods of time and limited
spatial scales even though spatiotemporal variation is common. Here, we
characterized assortative mating patterns over 10 years in four populations of
the blue tit (Cyanistes caeruleus), a passerine bird. We focused on two plumage
ornaments-the blue crown and the yellow breast patch. Based on data for 1,657
pairs of birds, we found large interannual variation: assortative mating varied
from positive to negative. To determine whether there was nonetheless a general
trend in the data, we ran a within-study meta-analysis. It revealed that
assortative mating was moderately positive for both ornaments. It also showed
that mating patterns differed among populations and especially between two
neighboring populations that displayed phenotypic divergence. Our results
therefore underscore that long-term studies are needed to draw broad conclusions
about mating patterns in natural populations. They also call for studying the
potential role of assortative mating in local adaptation and evolution of
ornaments in both sexes.
PMID- 28405274
TI - Natal origin affects host preference and larval performance relationships in a
tritrophic system.
AB - Many insects face the challenge to select oviposition sites in heterogeneous
environments where biotic and abiotic factors can change over time. One way to
deal with this complexity is to use sensory experiences made during developmental
stages to locate similar habitats or hosts in which larval development can be
maximized. While various studies have investigated oviposition preference and
larval performance relationships in insects, they have largely overlooked that
sensory experiences made during the larval stage can affect such relationships.
We addressed this issue by determining the role of natal experience on
oviposition preference and larval performance relationships in a tritrophic
system consisting of Galerucella sagittariae, feeding on the two host plants
Potentilla palustris and Lysimachia thyrsiflora, and its larval parasitoid
Asecodes lucens. We firstly determined whether differences in host-derived
olfactory information could lead to divergent host selection, and secondly,
whether host preference could result in higher larval performance based on the
natal origin of the insects. Our results showed that the natal origin and the
quality of the current host are both important aspects in oviposition preference
and larval performance relationships. While we found a positive relationship
between preference and performance for natal Lysimachia beetles, natal Potentilla
larvae showed no such relationship and developed better on L. thyrsiflora.
Additionally, the host selection by the parasitoid was mainly affected by the
natal origin, while its performance was higher on Lysimachia larvae. With this
study, we showed that the relationship between oviposition preference and larval
performance depends on the interplay between the natal origin of the female and
the quality of the current host. However, without incorporating the full
tritrophic context of these interactions, their implication in insect fitness and
potential adaptation cannot be fully understood.
PMID- 28405275
TI - The reproductive potential and importance of key management aspects for
successful Calluna vulgaris rejuvenation on abandoned Continental heaths.
AB - The abandonment of traditional pastoralism as well as the use of heath areas for
military purposes has had a major impact on dry heaths in the Continental
biogeographical region of Europe, causing severe degradation of its key species
Calluna vulgaris (L.) HULL. The reproductive potential of this species in a
Continental climate is assumed to be low, although there is yet no observational
or experimental evidence for this. More knowledge is also needed about cost
effective and sustainable measures to restore abandoned dry heaths in this
biogeographical region, because traditional management options are often too
expensive (e.g., sod-cutting) or restricted due to environmental laws and the
danger of unexploded ammunition (e.g., burning). Using as an example an 800 ha
Continental heathland in Germany that has been abandoned for about two decades,
we studied the reproductive potential (seed production, soil seed bank, and
germination ability) of degenerate C. vulgaris stands. In addition, we conducted
a comprehensive field experiment to test the effects of low-intensity, year-round
grazing by Heck cattle and Konik horses as well as one-time mowing and patchy
exposure of bare soil on the generative rejuvenation (i.e., recruitment and
survival) of degenerate C. vulgaris stands over 3 years. We used generalized
linear mixed models for statistical analyses. Seed production of degenerate C.
vulgaris stands was high as well as the germination ability of their seeds, being
similar to Atlantic heathlands. However, soil seed-bank densities were lower than
those found in managed or abandoned Atlantic heaths. Overall seedling recruitment
in the field was considerably lower in comparison with Atlantic heaths. Low
intensity grazing or one-time mowing did not induce a substantial increase in C.
vulgaris recruitment, whereas an additional one-time creation of bare soil
patches or the one-time creation of bare soil without subsequent management
significantly facilitated seedling recruitment and survival in the first year.
However, from the second year on, the positive effect of the creation of bare
soil without subsequent management was no longer present. In the third year,
survival of juveniles was significantly supported by low-intensity grazing in
combination with shallow soil disturbances as well as in combination with one
time mowing and shallow soil disturbances, whereas mowing alone resulted in
marginally significant lower survival. The extremely low seedling recruitment
requires a careful choice of suitable management measures to promote the survival
of sufficient numbers of Calluna individuals. Therefore, we recommend low
intensity grazing with free-ranging robust breeds and the combination of this
with one-time mowing as an effective means of supporting generative rejuvenation
of C. vulgaris in degraded heaths. However, at the beginning of the restoration
process, the creation of bare soil patches for seedling recruitment is crucial.
For implementation into practice, we present different strategies to enhance the
proportion of bare soil after long-term abandonment of heaths when traditional
management options are no longer feasible.
PMID- 28405276
TI - A simulation approach to assessing environmental risk of sound exposure to marine
mammals.
AB - Intense underwater sounds caused by military sonar, seismic surveys, and pile
driving can harm acoustically sensitive marine mammals. Many jurisdictions
require such activities to undergo marine mammal impact assessments to guide
mitigation. However, the ability to assess impacts in a rigorous, quantitative
way is hindered by large knowledge gaps concerning hearing ability, sensitivity,
and behavioral responses to noise exposure. We describe a simulation-based
framework, called SAFESIMM (Statistical Algorithms For Estimating the Sonar
Influence on Marine Megafauna), that can be used to calculate the numbers of
agents (animals) likely to be affected by intense underwater sounds. We
illustrate the simulation framework using two species that are likely to be
affected by marine renewable energy developments in UK waters: gray seal
(Halichoerus grypus) and harbor porpoise (Phocoena phocoena). We investigate
three sources of uncertainty: How sound energy is perceived by agents with
differing hearing abilities; how agents move in response to noise (i.e., the
strength and directionality of their evasive movements); and the way in which
these responses may interact with longer term constraints on agent movement. The
estimate of received sound exposure level (SEL) is influenced most strongly by
the weighting function used to account for the specie's presumed hearing ability.
Strongly directional movement away from the sound source can cause modest
reductions (~5 dB) in SEL over the short term (periods of less than 10 days).
Beyond 10 days, the way in which agents respond to noise exposure has little or
no effect on SEL, unless their movements are constrained by natural boundaries.
Most experimental studies of noise impacts have been short-term. However, data
are needed on long-term effects because uncertainty about predicted SELs
accumulates over time. Synthesis and applications. Simulation frameworks offer a
powerful way to explore, understand, and estimate effects of cumulative sound
exposure on marine mammals and to quantify associated levels of uncertainty.
However, they can often require subjective decisions that have important
consequences for management recommendations, and the basis for these decisions
must be clearly described.
PMID- 28405277
TI - A hidden Markov movement model for rapidly identifying behavioral states from
animal tracks.
AB - Electronic telemetry is frequently used to document animal movement through time.
Methods that can identify underlying behaviors driving specific movement patterns
can help us understand how and why animals use available space, thereby aiding
conservation and management efforts. For aquatic animal tracking data with
significant measurement error, a Bayesian state-space model called the first
Difference Correlated Random Walk with Switching (DCRWS) has often been used for
this purpose. However, for aquatic animals, highly accurate tracking data are now
becoming more common. We developed a new hidden Markov model (HMM) for
identifying behavioral states from animal tracks with negligible error, called
the hidden Markov movement model (HMMM). We implemented as the basis for the HMMM
the process equation of the DCRWS, but we used the method of maximum likelihood
and the R package TMB for rapid model fitting. The HMMM was compared to a
modified version of the DCRWS for highly accurate tracks, the DCRWSNOME, and to a
common HMM for animal tracks fitted with the R package moveHMM. We show that the
HMMM is both accurate and suitable for multiple species by fitting it to real
tracks from a grey seal, lake trout, and blue shark, as well as to simulated
data. The HMMM is a fast and reliable tool for making meaningful inference from
animal movement data that is ideally suited for ecologists who want to use the
popular DCRWS implementation and have highly accurate tracking data. It
additionally provides a groundwork for development of more complex modeling of
animal movement with TMB. To facilitate its uptake, we make it available through
the R package swim.
PMID- 28405278
TI - Seasonal patterns in reproductive success of temperate-breeding birds:
Experimental tests of the date and quality hypotheses.
AB - For organisms in seasonal environments, individuals that breed earlier in the
season regularly attain higher fitness than their late-breeding counterparts. Two
primary hypotheses have been proposed to explain these patterns: The quality
hypothesis contends that early breeders are of better phenotypic quality or breed
on higher quality territories, whereas the date hypothesis predicts that
seasonally declining reproductive success is a response to a seasonal
deterioration in environmental quality. In birds, food availability is thought to
drive deteriorating environmental conditions, but few experimental studies have
demonstrated its importance while also controlling for parental quality. We
tested predictions of the date hypothesis in tree swallows (Tachycineta bicolor)
over two breeding seasons and in two locations within their breeding range in
Canada. Nests were paired by clutch initiation date to control for parental
quality, and we delayed the hatching date of one nest within each pair.
Subsequently, brood sizes were manipulated to mimic changes in per capita food
abundance, and we examined the effects of manipulations, as well as indices of
environmental and parental quality, on nestling quality, fledging success, and
return rates. Reduced reproductive success of late-breeding individuals was
causally related to a seasonal decline in environmental quality. Declining insect
biomass and enlarged brood sizes resulted in nestlings that were lighter, in
poorer body condition, structurally smaller, had shorter and slower growing
flight feathers and were less likely to survive to fledge. Our results provide
evidence for the importance of food resources in mediating seasonal declines in
offspring quality and survival.
PMID- 28405279
TI - Fine-scale frequency differentiation along a herbivory gradient in the trichome
dimorphism of a wild Arabidopsis.
AB - Geographic variation is commonly observed in plant resistance traits, where plant
species might experience different selection pressure across a heterogeneous
landscape. Arabidopsis halleri subsp. gemmifera is dimorphic for trichome
production, generating two morphs, trichome-producing (hairy) and trichomeless
(glabrous) plants. Trichomes of A. halleri are known to confer resistance against
the white butterfly, cabbage sawfly, and brassica leaf beetle, but not against
flea beetles. We combined leaf damage, microclimate, and microsatellite loci data
of 26 A. halleri populations in central Japan, to explore factors responsible for
fine-scale geographic variation in the morph frequency. We found that hairy
plants were less damaged than glabrous plants within populations, but the among
site variation was the most significant source of variation in the individual
level damage. Fixation index (Gst") of a putative trichome locus exhibited a
significant divergence along population-level damage with an exception of an
outlier population, inferring the local adaptation to herbivory. Notably, this
outlier was a population wherein our previous study reported a balancing role of
the brassica leaf beetle Phaedon brassicae on the morph frequency. This
differentiation of the trichome locus was unrelated to neutral genetic
differentiation (evaluated by Gst" of microsatellite loci) and meteorological
factors (including temperature and solar radiation). The present findings,
combined with those of our previous work, provide suggestive evidence that
herbivore-driven divergence and occasional outbreak of a specific herbivore have
jointly contributed to the ecogeographic pattern in the frequency of two morphs.
PMID- 28405280
TI - Multiple environmental changes drive forest floor vegetation in a temperate
mountain forest.
AB - Human-induced changes of the environment and their possible impacts on temperate
forest understory plant communities have been examined in many studies. However,
the relative contribution of individual environmental factors to these changes in
the herb layer is still unclear. In this study, we used vegetation survey data
covering a time period of 21 years and collected from 143 permanent plots in the
Northern Limestone Alps, Austria. Data on soil chemistry (49 plots), light
condition (51 plots), soil temperature and moisture (four and six plots),
disturbance (all plots), climate (one station in a clearing area), and airborne
sulfur (S) and nitrogen (N) deposition (two forest stands) were available for
analyses. We used these data together with plot mean Ellenberg indicator values
in a path analysis to attribute their relative contributions to observed
vegetation changes. Our analysis reveals a strong directional shift of the forest
understory plant community. We found strong evidence for a recovery of the ground
layer vegetation from acidification as response to decreased S deposition. We did
not observe a community response to atmospheric N deposition, but we found a
response to altered climatic conditions (thermophilization and drying). The path
analysis revealed that changes in the light regime, which were related to small
scale disturbances, had most influence on herb layer community shifts.
Thermophilization and drying were identified as drivers of understory community
changes independent of disturbance events.
PMID- 28405281
TI - Patterns of genetic, phenotypic, and acoustic variation across a chiffchaff
(Phylloscopus collybita abietinus/tristis) hybrid zone.
AB - Characterizing patterns of evolution of genetic and phenotypic divergence between
incipient species is essential to understand how evolution of reproductive
isolation proceeds. Hybrid zones are excellent for studying such processes, as
they provide opportunities to assess trait variation in individuals with mixed
genetic background and to quantify gene flow across different genomic regions.
Here, we combine plumage, song, mtDNA and whole-genome sequence data and analyze
variation across a sympatric zone between the European and the Siberian
chiffchaff (Phylloscopus collybita abietinus/tristis) to study how gene exchange
between the lineages affects trait variation. Our results show that chiffchaff
within the sympatric region show more extensive trait variation than allopatric
birds, with a large proportion of individuals exhibiting intermediate phenotypic
characters. The genomic differentiation between the subspecies is lower in
sympatry than in allopatry and sympatric birds have a mix of genetic ancestry
indicating extensive ongoing and past gene flow. Patterns of phenotypic and
genetic variation also vary between regions within the hybrid zone, potentially
reflecting differences in population densities, age of secondary contact, or
differences in mate recognition or mate preference. The genomic data support the
presence of two distinct genetic clades corresponding to allopatric abietinus and
tristis and that genetic admixture is the force underlying trait variation in the
sympatric region-the previously described subspecies ("fulvescens") from the
region is therefore not likely a distinct taxon. In addition, we conclude that
subspecies identification based on appearance is uncertain as an individual with
an apparently distinct phenotype can have a considerable proportion of the genome
composed of mixed alleles, or even a major part of the genome introgressed from
the other subspecies. Our results provide insights into the dynamics of admixture
across subspecies boundaries and have implications for understanding speciation
processes and for the identification of specific chiffchaff individuals based on
phenotypic characters.
PMID- 28405282
TI - Ecological application of biotic resistance to control the invasion of an
invasive plant, Ageratina altissima.
AB - Biotic resistance is the ability of species in a community to limit the invasion
of other species. However, biotic resistance is not widely used to control
invasive plants. Experimental, functional, and modeling approaches were combined
to investigate the processes of invasion by Ageratina altissima (white
snakeroot), a model invasive species in South Korea. We hypothesized that (1)
functional group identity would be a good predictor of biotic resistance to A.
altissima, whereas a species identity effect would be redundant within a
functional group, and (2) mixtures of species would be more resistant to invasion
than monocultures. We classified 37 species of native plants into three
functional groups based on seven functional traits. The classification of
functional groups was based primarily on differences in life longevity and
woodiness. A competition experiment was conducted based on an additive
competition design with A. altissima and monocultures or mixtures of resident
plants. As an indicator of biotic resistance, we calculated a relative
competition index (RCI avg) based on the average performance of A. altissima in a
competition treatment compared with that of the control where only seeds of A.
altissima were sown. To further explain the effect of diversity, we tested
several diversity-interaction models. In monoculture treatments, RCI avg of
resident plants was significantly different among functional groups but not
within each functional group. Fast-growing annuals (FG1) had the highest RCI avg,
suggesting priority effects (niche pre-emption). RCI avg of resident plants was
significantly greater in a mixture than in a monoculture. According to the
diversity-interaction models, species interaction patterns in mixtures were best
described by interactions between functional groups, which implied niche
partitioning. Functional group identity and diversity of resident plant
communities were good indicators of biotic resistance to invasion by introduced
A. altissima, with the underlying mechanisms likely niche pre-emption and niche
partitioning. This method has most potential in assisted restoration contexts,
where there is a desire to reintroduce natives or boost their population size due
to some previous level of degradation.
PMID- 28405283
TI - Anolis lizards as biocontrol agents in mainland and island agroecosystems.
AB - Our knowledge of ecological interactions that bolster ecosystem function and
productivity has broad applications to the management of agricultural systems.
Studies suggest that the presence of generalist predators in agricultural
landscapes leads to a decrease in the abundance of herbivorous pests, but our
understanding of how these interactions vary across taxa and along gradients of
management intensity and eco-geographic space remains incomplete. In this study,
we assessed the functional response and biocontrol potential of a highly
ubiquitous insectivore (lizards in the genus Anolis) on the world's most
important coffee pest, the coffee berry borer (Hypothalemus hampei). We conducted
field surveys and laboratory experiments to examine the impact of land-use
intensification on species richness and abundance of anoles and the capacity of
anoles to reduce berry borer infestations in mainland and island coffee systems.
Our results show that anoles significantly reduce coffee infestation rates in
laboratory settings (Mexico, p = .03, F = 5.13 df = 1, 35; Puerto Rico, p = .014,
F = 8.82, df = 1, 10) and are capable of consuming coffee berry borers in high
abundance. Additionally, diversified agroecosystems bolster anole abundance,
while high-intensity practices, including the reduction of vegetation complexity
and the application of agrochemicals were associated with reduced anole
abundance. The results of this study provide supporting evidence of the positive
impact of generalist predators on the control of crop pests in agricultural
landscapes, and the role of diversified agroecosystems in sustaining both
functionally diverse communities and crop production in tropical agroecosystems.
PMID- 28405284
TI - Role of breeding and natal movements in lifetime dispersal of a forest-dwelling
rodent.
AB - The lifetime movements of an individual determine the gene flow and invasion
potential of the species. However, sex dependence of dispersal and selective
pressures driving dispersal have gained much more attention than dispersal at
different life and age stages. Natal dispersal is more common than dispersal
between breeding attempts, but breeding dispersal may be promoted by resource
availability and competition. Here, we utilize mark-recapture data on the nest
box population of Siberian flying squirrels to analyze lifetime dispersal
patterns. Natal dispersal means the distance between the natal nest and the nest
used the following year, whereas breeding movements refer to the nest site
changes between breeding attempts. The movement distances observed here were
comparable to distances reported earlier from radio-telemetry studies. Breeding
movements did not contribute to lifetime dispersal distance and were not related
to variation in food abundance or habitat patch size. Breeding movements of males
were negatively, albeit not strongly, related to male population size. In
females, breeding movement activity was low and was not related to previous
breeding success or to competition between females for territories. Natal
philopatry was linked to apparent death of a mother; that is, we did not find
evidence for mothers bequeathing territories for offspring, like observed in some
other rodent species. Our results give an example of a species in which breeding
movements are not driven by environmental variability or nest site quality.
Different evolutionary forces often operate in natal and breeding movements, and
our study supports the view that juveniles are responsible for redistributing
individuals within and between populations. This emphasizes the importance of
knowledge on natal dispersal, if we want to understand consequences of movement
ecology of the species at the population level.
PMID- 28405285
TI - Habitat suitability and demography, a time-dependent relationship.
AB - The habitat suitability index, which reflects spatial variability in species
occurrence probability, has been shown to exhibit various contrasting
relationships with local demographic performances (survival, productivity) in
several species. One proposed explanation for these discrepancies is that the
link between the habitat suitability index and demography is influenced by
density-dependent, temporally variable processes. Based on the survival rates of
more than 3,000 nests monitored over 12 years in the North African Houbara
Bustard, we investigated whether the habitat suitability index computed over the
species breeding range is related to nest survival throughout the breeding
season, accounting for variation in meteorological conditions. We found that the
relationship between the habitat suitability index and nest survival
progressively changes along the breeding season and that this intra-annual
variation is consistent between years. Our results support the hypothesis that
variation in space use occurs intra-annually and that biotic interactions
throughout the breeding season strongly influence the habitat suitability index
demography relationship.
PMID- 28405286
TI - Predicting species establishment using absent species and functional
neighborhoods.
AB - Species establishment within a community depends on their interactions with the
local environment and resident community. Such environmental and biotic filtering
is frequently inferred from functional trait and phylogenetic patterns within
communities; these patterns may also predict which additional species can
establish. However, differentiating between environmental and biotic filtering
can be challenging, which may complicate establishment predictions. Creating a
habitat-specific species pool by identifying which absent species within the
region can establish in the focal habitat allows us to isolate biotic filtering
by modeling dissimilarity between the observed and biotically excluded species
able to pass environmental filters. Similarly, modeling the dissimilarity between
the habitat-specific species pool and the environmentally excluded species within
the region can isolate local environmental filters. Combined, these models
identify potentially successful phenotypes and why certain phenotypes were
unsuccessful. Here, we present a framework that uses the functional dissimilarity
among these groups in logistic models to predict establishment of additional
species. This approach can use multivariate trait distances and phylogenetic
information, but is most powerful when using individual traits and their
interactions. It also requires an appropriate distance-based dissimilarity
measure, yet the two most commonly used indices, nearest neighbor (one species)
and mean pairwise (all species) distances, may inaccurately predict
establishment. By iteratively increasing the number of species used to measure
dissimilarity, a functional neighborhood can be chosen that maximizes the
detection of underlying trait patterns. We tested this framework using two seed
addition experiments in calcareous grasslands. Although the functional
neighborhood size that best fits the community's trait structure depended on the
type of filtering considered, selecting these functional neighborhood sizes
allowed our framework to predict up to 50% of the variation in actual
establishment from seed. These results indicate that the proposed framework may
be a powerful tool for studying and predicting species establishment.
PMID- 28405287
TI - The impact of climate change on the distribution of two threatened Dipterocarp
trees.
AB - Two ecologically and economically important, and threatened Dipterocarp trees Sal
(Shorea robusta) and Garjan (Dipterocarpus turbinatus) form mono-specific
canopies in dry deciduous, moist deciduous, evergreen, and semievergreen forests
across South Asia and continental parts of Southeast Asia. They provide valuable
timber and play an important role in the economy of many Asian countries.
However, both Dipterocarp trees are threatened by continuing forest clearing,
habitat alteration, and global climate change. While climatic regimes in the
Asian tropics are changing, research on climate change-driven shifts in the
distribution of tropical Asian trees is limited. We applied a bioclimatic
modeling approach to these two Dipterocarp trees Sal and Garjan. We used presence
only records for the tree species, five bioclimatic variables, and selected two
climatic scenarios (RCP4.5: an optimistic scenario and RCP8.5: a pessimistic
scenario) and three global climate models (GCMs) to encompass the full range of
variation in the models. We modeled climate space suitability for both species,
projected to 2070, using a climate envelope modeling tool "MaxEnt" (the maximum
entropy algorithm). Annual precipitation was the key bioclimatic variable in all
GCMs for explaining the current and future distributions of Sal and Garjan (Sal:
49.97 +/- 1.33; Garjan: 37.63 +/- 1.19). Our models predict that suitable climate
space for Sal will decline by 24% and 34% (the mean of the three GCMs) by 2070
under RCP4.5 and RCP8.5, respectively. In contrast, the consequences of imminent
climate change appear less severe for Garjan, with a decline of 17% and 27% under
RCP4.5 and RCP8.5, respectively. The findings of this study can be used to set
conservation guidelines for Sal and Garjan by identifying vulnerable habitats in
the region. In addition, the natural habitats of Sal and Garjan can be
categorized as low to high risk under changing climates where artificial
regeneration should be undertaken for forest restoration.
PMID- 28405288
TI - Wood ants produce a potent antimicrobial agent by applying formic acid on tree
collected resin.
AB - Wood ants fight pathogens by incorporating tree resin with antimicrobial
properties into their nests. They also produce large quantities of formic acid in
their venom gland, which they readily spray to defend or disinfect their nest.
Mixing chemicals to produce powerful antibiotics is common practice in human
medicine, yet evidence for the use of such "defensive cocktails" by animals
remains scant. Here, we test the hypothesis that wood ants enhance the antifungal
activity of tree resin by treating it with formic acid. In a series of
experiments, we document that (i) tree resin had much higher inhibitory activity
against the common entomopathogenic fungus Metarhizium brunneum after having been
in contact with ants, while no such effect was detected for other nest materials;
(ii) wood ants applied significant amounts of endogenous formic and succinic acid
on resin and other nest materials; and (iii) the application of synthetic formic
acid greatly increased the antifungal activity of resin, but had no such effect
when applied to inert glass material. Together, these results demonstrate that
wood ants obtain an effective protection against a detrimental microorganism by
mixing endogenous and plant-acquired chemical defenses. In conclusion, the
ability to synergistically combine antimicrobial substances of diverse origins is
not restricted to humans and may play an important role in insect societies.
PMID- 28405289
TI - Oxygen and carbon isoscapes for the Baltic Sea: Testing their applicability in
fish migration studies.
AB - Conventional tags applied to individuals have been used to investigate animal
movement, but these methods require tagged individuals be recaptured. Maps of
regional isotopic variability known as "isoscapes" offer potential for various
applications in migration research without tagging wherein isotope values of
tissues are compared to environmental isotope values. In this study, we present
the spatial variability in oxygen (delta18OH2O) and dissolved inorganic carbon
(delta13 CDIC) isotope values of Baltic Sea water. We also provide an example of
how these isoscapes can reveal locations of individual animal via spatial
probability surface maps, using the high-resolution salmon otolith isotope data
from salmon during their sea-feeding phase in the Baltic Sea. A clear latitudinal
and vertical gradient was found for both delta18OH2O and delta13 CDIC values. The
difference between summer and winter in the Baltic Sea delta18OH2O values was
only slight, whereas delta13 CDIC values exhibited substantial seasonal
variability related to algal productivity. Salmon otolith delta18Ooto and
delta13Coto values showed clear differences between feeding areas and seasons.
Our example demonstrates that dual isotope approach offers great potential for
estimating probable fish habitats once issues in model parameterization have been
resolved.
PMID- 28405290
TI - Reproductive interference by male Drosophila subobscura on female D. persimilis:
A laboratory experiment.
AB - While females often reject courtship attempts by heterospecific males,
reproductive interference by harassment from such males can nonetheless occur,
potentially reducing female fitness. Such effects may be profound following a
range expansion, when males from a new species may suddenly encounter (and
perhaps even become abundant relative to) females of related native species.
Drosophila subobscura recently invaded North America and may impact native
species through reproductive interference and other processes. We test for the
potential for reproductive interference by D. subobscura males on D. persimilis
females in the laboratory. D. subobscura males aggressively copulated with D.
persimilis females, including many females that exhibit rejection behaviors.
Despite females attempting to dismount the males, the heterospecific copulations
are on average longer than conspecific copulations, and females exhibit some
reluctance to remate with conspecific males following this harassment. Females
confined with both conspecific and heterospecific males produce fewer adult
progeny than those with either conspecific males only or with conspecific males
and distantly related D. simulans males that do not engage in female harassment.
Overall, our results illustrate how reproductive interference by an invasive
species can have negative effects on resident natural populations.
PMID- 28405291
TI - Trait dimensionality and population choice alter estimates of phenotypic
dissimilarity.
AB - The ecological niche is a multi-dimensional concept including aspects of resource
use, environmental tolerance, and interspecific interactions, and the degree to
which niches overlap is central to many ecological questions. Plant phenotypic
traits are increasingly used as surrogates of species niches, but we lack an
understanding of how key sampling decisions affect our ability to capture
phenotypic differences among species. Using trait data of ecologically distinct
monkeyflower (Mimulus) congeners, we employed linear discriminant analysis to
determine how (1) dimensionality (the number and type of traits) and (2)
variation within species influence how well measured traits reflect phenotypic
differences among species. We conducted analyses using vegetative and floral
traits in different combinations of up to 13 traits and compared the performance
of commonly used functional traits such as specific leaf area against other
morphological traits. We tested the importance of intraspecific variation by
assessing how population choice changed our ability to discriminate species.
Neither using key functional traits nor sampling across plant functions and
organs maximized species discrimination. When using few traits, vegetative traits
performed better than combinations of vegetative and floral traits or floral
traits alone. Overall, including more traits increased our ability to detect
phenotypic differences among species. Population choice and the number of traits
used had comparable impacts on discriminating species. We addressed
methodological challenges that have undermined cross-study comparability of trait
based approaches. Our results emphasize the importance of sampling among
population trait variation and suggest that a high-dimensional approach may best
capture phenotypic variation among species with distinct niches.
PMID- 28405292
TI - Effects of genetically modified maize events expressing Cry34Ab1, Cry35Ab1,
Cry1F, and CP4 EPSPS proteins on arthropod complex food webs.
AB - Four genetically modified (GM) maize (Zea mays L.) hybrids (coleopteran
resistant, coleopteran and lepidopteran resistant, lepidopteran resistant and
herbicide tolerant, coleopteran and herbicide tolerant) and its non-GM control
maize stands were tested to compare the functional diversity of arthropods and to
determine whether genetic modifications alter the structure of arthropods food
webs. A total number of 399,239 arthropod individuals were used for analyses. The
trophic groups' number and the links between them indicated that neither the
higher magnitude of Bt toxins (included resistance against insect, and against
both insects and glyphosate) nor the extra glyphosate treatment changed the
structure of food webs. However, differences in the average trophic links/trophic
groups were detected between GM and non-GM food webs for herbivore groups and
plants. Also, differences in characteristic path lengths between GM and non-GM
food webs for herbivores were observed. Food webs parameterized based on 2-year
in-field assessments, and their properties can be considered a useful and simple
tool to evaluate the effects of Bt toxins on non-target organisms.
PMID- 28405293
TI - Community assembly in Nothobranchius annual fishes: Nested patterns,
environmental niche and biogeographic history.
AB - The assembly of local communities from regional species pools is shaped by
historical aspects of distribution, environmental conditions, and biotic
interactions. We studied local community assembly patterns in African annual
killifishes of the genus Nothobranchius (Cyprinodontiformes), investigating data
from 168 communities across the entire range of regionally co-existing species.
Nothobranchius are small fishes associated with annually desiccating pools. We
detected a nested pattern of local communities in one region (Southern
Mozambique, with Nothobranchius furzeri as the core and dominant species), but no
nestedness was found in the second region (Central Mozambique, with
Nothobranchius orthonotus being the dominant species). A checkerboard pattern of
local Nothobranchius community assembly was demonstrated in both regions.
Multivariate environmental niche modeling revealed moderate differences in
environmental niche occupancy between three monophyletic clades that largely co
occurred geographically and greater differences between strictly allopatric
species within the clades. Most variation among species was observed along an
altitudinal gradient; N. furzeri and Nothobranchius kadleci were absent from
coastal plains, Nothobranchius pienaari, Nothobranchius rachovii, and
Nothobranchius krysanovi were associated with lower altitude and N. orthonotus
was intermediate and geographically most widespread species. We discuss
implications for ecological and evolutionary research in this taxon.
PMID- 28405294
TI - Dissecting Solidago canadensis-soil feedback in its real invasion.
AB - The importance of plant-soil feedback (PSF) has long been recognized, but the
current knowledge on PSF patterns and the related mechanisms mainly stems from
laboratory experiments. We aimed at addressing PSF effects on community
performance and their determinants using an invasive forb Solidago canadensis. To
do so, we surveyed 81 pairs of invaded versus uninvaded plots, collected soil
samples from these pairwise plots, and performed an experiment with microcosm
plant communities. The magnitudes of conditioning soil abiotic properties and
soil biotic properties by S. canadensis were similar, but the direction was
opposite; altered abiotic and biotic properties influenced the production of
subsequent S. canadensis communities and its abundance similarly. These processes
shaped neutral S. canadensis-soil feedback effects at the community level.
Additionally, the relative dominance of S. canadensis increased with its ability
of competitive suppression in the absence and presence of S. canadensis-soil
feedbacks, and S. canadensis-induced decreases in native plant species did not
alter soil properties directly. These findings provide a basis for understanding
PSF effects and the related mechanisms in the field conditions and also highlight
the importance of considering PSFs holistically.
PMID- 28405295
TI - Flight performance in the altricial zebra finch: Developmental effects and
reproductive consequences.
AB - The environmental conditions animals experience during development can have
sustained effects on morphology, physiology, and behavior. Exposure to elevated
levels of stress hormones (glucocorticoids, GCs) during development is one such
condition that can have long-term effects on animal phenotype. Many of the
phenotypic effects of GC exposure during development (developmental stress)
appear negative. However, there is increasing evidence that developmental stress
can induce adaptive phenotypic changes. This hypothesis can be tested by
examining the effect of developmental stress on fitness-related traits. In birds,
flight performance is an ideal metric to assess the fitness consequences of
developmental stress. As fledglings, mastering takeoff is crucial to avoid bodily
damage and escape predation. As adults, takeoff can contribute to mating and
foraging success as well as escape and, thus, can affect both reproductive
success and survival. We examined the effects of developmental stress on flight
performance across life-history stages in zebra finches (Taeniopygia guttata).
Specifically, we examined the effects of oral administration of corticosterone
(CORT, the dominant avian glucocorticoid) during development on ground-reaction
forces and velocity during takeoff. Additionally, we tested for associations
between flight performance and reproductive success in adult male zebra finches.
Developmental stress had no effect on flight performance at all ages. In
contrast, brood size (an unmanipulated variable) had sustained, negative effects
on takeoff performance across life-history stages with birds from small broods
performing better than birds from large broods. Flight performance at 100 days
posthatching predicted future reproductive success in males; the best fliers had
significantly higher reproductive success. Our results demonstrate that some
environmental factors experienced during development (e.g. clutch size) have
stronger, more sustained effects than others (e.g. GC exposure). Additionally,
our data provide the first link between flight performance and a direct measure
of reproductive success.
PMID- 28405296
TI - Consumptive and nonconsumptive effect ratios depend on interaction between plant
quality and hunting behavior of omnivorous predators.
AB - Predators not only consume prey but exert nonconsumptive effects in form of
scaring, consequently disturbing feeding or reproduction. However, how
alternative food sources and hunting mode interactively affect consumptive and
nonconsumptive effects with implications for prey fitness have not been
addressed, impending functional understanding of such tritrophic interactions.
With a herbivorous beetle, two omnivorous predatory bugs (plant sap as
alternative food, contrasting hunting modes), and four willow genotypes
(contrasting suitability for beetle/omnivore), we investigated direct and
indirect effects of plant quality on the beetles key reproductive traits
(oviposition rate, clutch size). Using combinations of either or both omnivores
on different plant genotypes, we calculated the contribution of consumptive (eggs
predated) and nonconsumptive (fewer eggs laid) effect on beetle fitness,
including a prey density-independent measure (c:nc ratio). We found that larger
clutches increase egg survival in presence of the omnivore not immediately
consuming all eggs. However, rather than lowering mean, the beetles generally
responded with a frequency shift toward smaller clutches. However, female beetles
decreased mean and changed clutch size frequency with decreasing plant quality,
therefore reducing intraspecific exploitative competition among larvae. More
importantly, variation in host plant quality (to omnivore) led to nonconsumptive
effects between one-third and twice as strong as the consumptive effects.
Increased egg consumption on plants less suitable to the omnivore may therefore
be accompanied by less searching and disturbing the beetle, representing a "cost"
to the indirect plant defense in the form of a lower nonconsumptive effect. Many
predators are omnivores and altering c:nc ratios (with egg retention as the most
direct link to prey fitness) via plant quality and hunting behavior should be
fundamental to advance ecological theory and applications. Furthermore, exploring
modulation of fitness traits by bottom-up and top-down effects will help to
explain how and why species aggregate.
PMID- 28405297
TI - Sex change in the subdioecious shrub Eurya japonica (Pentaphylacaceae).
AB - Sex change affects the sex ratios of plant populations and may play an essential
role in the evolutionary shift of sexual systems. Sex change can be a strategy
for increasing fitness over the lifetime of a plant, and plant size,
environmental factors, and growth rate may affect sex change. We described
frequent, repeated sex changes following various patterns in a subdioecious Eurya
japonica population over five successive years. Of the individuals, 27.5% changed
their sex at least once, and these changes were unidirectional or bidirectional.
The sex ratio (females/males/all hermaphrodite types) did not fluctuate over the
5 years. In our study plots, although the current sex ratio among the sexes
appears to be stable, the change in sex ratio may be slowly progressing toward
increasing females and decreasing males. Sex was more likely to change with
higher growth rates and more exposure to light throughout the year. Among
individuals that changed sex, those that were less exposed to light in the leafy
season and had less diameter growth tended to shift from hermaphrodite to a
single sex. Therefore, sex change in E. japonica seemed to be explained by a
response to the internal physiological condition of an individual mediated by
intrinsic and abiotic environmental factors.
PMID- 28405298
TI - Seasonal and temperature-related movement of Colorado River cutthroat trout in a
low-elevation, Rocky Mountain stream.
AB - Mobile species will migrate considerable distances to find habitats suitable for
meeting life history requirements, and stream-dwelling salmonids are no
exception. In April-October 2014, we used radio-telemetry to examine habitat use
and movement of 36 Colorado River cutthroat trout Oncorhynchus clarkii
pleuriticus (CRCT) in a 14.9-km fragment of Milk Creek, a relatively low
elevation stream in the Rocky Mountains (Colorado). We also used a network of
data loggers to track stream temperature across time and space. Our objectives
were to (1) characterize distribution and movement of CRCT, (2) evaluate seasonal
differences in distribution and movement of CRCT, and (3) explore the
relationship between stream temperature and distribution and movement of CRCT.
During the course of our study, median range of CRCT was 4.81 km (range = 0.14
10.94) and median total movement was 5.94 km (range = 0.14-26.02). Median
location of CRCT was significantly further upstream in summer than in spring,
whereas range and movement of CRCT were greater in spring than in summer. Twenty
six of the 27 CRCT tracked through mid-June displayed a potamodromous (freshwater
migratory) life history, migrating 1.8-8.0 km upstream during the spring spawning
season. Four of the seven CRCT tracked through July migrated >1.4 km in summer.
CRCT selected relatively cool reaches during summer months, and early-summer
movement was positively correlated with mean stream temperature. Study fish
occupied stream segments in spring and fall that were thermally unsuitable, if
not lethal, to the species in summer. Although transmitter loss limited the scope
of inference, our findings suggest that preferred habitat is a moving target in
Milk Creek, and that CRCT move to occupy that target. Because mobile organisms
move among complementary habitats and exploit seasonally-unsuitable reaches, we
recommend that spatial and temporal variability be accounted for in delineations
of distributional boundaries.
PMID- 28405299
TI - Multifunctionality is affected by interactions between green roof plant species,
substrate depth, and substrate type.
AB - Green roofs provide ecosystem services through evapotranspiration and nutrient
cycling that depend, among others, on plant species, substrate type, and
substrate depth. However, no study has assessed thoroughly how interactions
between these factors alter ecosystem functions and multifunctionality of green
roofs. We simulated some green roof conditions in a pot experiment. We planted 20
plant species from 10 genera and five families (Asteraceae, Caryophyllaceae,
Crassulaceae, Fabaceae, and Poaceae) on two substrate types (natural vs.
artificial) and two substrate depths (10 cm vs. 30 cm). As indicators of major
ecosystem functions, we measured aboveground and belowground biomasses, foliar
nitrogen and carbon content, foliar transpiration, substrate water retention, and
dissolved organic carbon and nitrates in leachates. Interactions between
substrate type and depth strongly affected ecosystem functions. Biomass
production was increased in the artificial substrate and deeper substrates, as
was water retention in most cases. In contrast, dissolved organic carbon leaching
was higher in the artificial substrates. Except for the Fabaceae species, nitrate
leaching was reduced in deep, natural soils. The highest transpiration rates were
associated with natural soils. All functions were modulated by plant families or
species. Plant effects differed according to the observed function and the type
and depth of the substrate. Fabaceae species grown on natural soils had the most
noticeable patterns, allowing high biomass production and high water retention
but also high nitrate leaching from deep pots. No single combination of factors
enhanced simultaneously all studied ecosystem functions, highlighting that soil
plant interactions induce trade-offs between ecosystem functions. Substrate type
and depth interactions are major drivers for green roof multifunctionality.
PMID- 28405301
TI - Canada lynx use of burned areas: Conservation implications of changing fire
regimes.
AB - A fundamental problem in ecology is forecasting how species will react to major
disturbances. As the climate warms, large, frequent, and severe fires are
restructuring forested landscapes at large spatial scales, with unknown impacts
on imperilled predators. We use the United States federally Threatened Canada
lynx as a case study to examine how predators navigate recent large burns, with
particular focus on habitat features and the spatial configuration (e.g.,
distance to edge) that enabled lynx use of these transformed landscapes. We
coupled GPS location data of lynx in Washington in an area with several recent
large fires and a number of GIS layers of habitat data to develop models of lynx
habitat selection in recent burns. Random Forest habitat models showed lynx
selected islands of forest skipped by large fires, residual vegetation, and areas
where some trees survived to use newly burned areas. Lynx used burned areas as
early as 1 year postfire, which is much earlier than the 2-4 decades postfire
previously thought for this predator. These findings are encouraging for predator
persistence in the face of fires, but increasingly severe fires or management
that reduces postfire residual trees or slow regeneration will likely jeopardize
lynx and other predators. Fire management should change to ensure heterogeneity
is retained within the footprint of large fires to enable viable predator
populations as fire regimes worsen with climate change.
PMID- 28405300
TI - Outlier analyses to test for local adaptation to breeding grounds in a migratory
arctic seabird.
AB - Investigating the extent (or the existence) of local adaptation is crucial to
understanding how populations adapt. When experiments or fitness measurements are
difficult or impossible to perform in natural populations, genomic techniques
allow us to investigate local adaptation through the comparison of allele
frequencies and outlier loci along environmental clines. The thick-billed murre
(Uria lomvia) is a highly philopatric colonial arctic seabird that occupies a
significant environmental gradient, shows marked phenotypic differences among
colonies, and has large effective population sizes. To test whether thick-billed
murres from five colonies along the eastern Canadian Arctic coast show genomic
signatures of local adaptation to their breeding grounds, we analyzed geographic
variation in genome-wide markers mapped to a newly assembled thick-billed murre
reference genome. We used outlier analyses to detect loci putatively under
selection, and clustering analyses to investigate patterns of differentiation
based on 2220 genomewide single nucleotide polymorphisms (SNPs) and 137 outlier
SNPs. We found no evidence of population structure among colonies using all loci
but found population structure based on outliers only, where birds from the two
northernmost colonies (Minarets and Prince Leopold) grouped with birds from the
southernmost colony (Gannet), and birds from Coats and Akpatok were distinct from
all other colonies. Although results from our analyses did not support local
adaptation along the latitudinal cline of breeding colonies, outlier loci grouped
birds from different colonies according to their non-breeding distributions,
suggesting that outliers may be informative about adaptation and/or demographic
connectivity associated with their migration patterns or nonbreeding grounds.
PMID- 28405302
TI - Breeding behavior of female white-tailed deer relative to conception: Evidence
for female mate choice.
AB - Female white-tailed deer (Odocoileus virginianus) are thought to choose between
two behavioral strategies to maximize the quality of potential mates: sit and
wait, characterized by concentrating activity within a restricted area, and
excursive behavior, characterized by increased activity and excursions outside
the home range. As movement patterns may influence conception, our goal was to
examine the patterns of female white-tailed deer movements to evaluate which
breeding strategy was employed. We equipped 36 female white-tailed deer with GPS
collars from August 2013 to December 2015. We found that movement rate and
probability of activity were greatest near the peak of the breeding season, and
we observed increases in both metrics during the 40 days prior to estimated
conception. Peak size of home range and core area occurred in the days
surrounding conception. We found that 11 deer performed an excursion, ranging
from 43 days before until 36 days after conception, with the peak probability of
being outside of an individual home range occurring 1 day prior to conception.
Our results suggest that female white-tailed deer may attempt to maximize the
quality of their mates by advertising availability for breeding through excursive
behaviors just prior to entering estrus.
PMID- 28405303
TI - Evaluating multiple spatial scales to understand the distribution of anuran beta
diversity in the Brazilian Atlantic Forest.
AB - We partitioned the total beta diversity in the species composition of anuran
tadpoles to evaluate if species replacement and nestedness components are
congruent at different spatial resolutions in the Brazilian Atlantic Forest. We
alternated the sampling grain and extent of the study area (among ponds at a
site, among ponds within regions, among sites within regions, and among sites
within regions pooled together) to assess the importance of anuran beta diversity
components. We then performed variation partitioning to evaluate the congruence
of environmental descriptors and geographical distance in explaining the spatial
distribution of the species replacement and nestedness components. We found that
species replacement was the main component of beta diversity, independent of the
sampling grain and extent. Furthermore, when considering the same sampling grain
and increasing the extent, the values of species replacement increased. On the
other hand, when considering the same extent and increasing the sampling grain,
the values of species replacement decreased. At the smallest sampling grain and
extent, the environmental descriptors and geographic distance were not congruent
and alternated in the percentage of variation explaining the spatial distribution
of species replacement and nestedness. At the largest spatial scales (SSs), the
biogeographical regions showed higher values of the percentage explaining the
variation in the beta diversity components. We found high values of species
replacement independently of the spatial resolution, but the processes driving
community assembly seem to be dependent on the SS. At small scales, both
stochastic and deterministic factors might be important processes structuring
anuran tadpole assemblages. On the other hand, at a large spatial grain and
extent, the processes restricting species distributions might be more effective
for drawing inferences regarding the variation in anuran beta diversity in
different regions of the Brazilian Atlantic Forest.
PMID- 28405304
TI - Reduced abundance and earlier collection of bumble bee workers under intensive
cultivation of a mass-flowering prairie crop.
AB - One of the most commonly seeded crops in Canada is canola, a cultivar of oilseed
rape (Brassica napus). As a mass-flowering crop grown intensively throughout the
Canadian Prairies, canola has the potential to influence pollinator success
across tens of thousands of square kilometers of cropland. Bumble bees (Bombus
sp.) are efficient pollinators of many types of native and crop plants. We
measured the influence of this mass-flowering crop on the abundance and phenology
of bumble bees, and on another species of social bee (a sweat bee; Halictus
rubicundus), by continuously deploying traps at different levels of canola
cultivation intensity, spanning the start and end of canola bloom. Queen bumble
bees were more abundant in areas with more canola cover, indicating that this
crop is attractive to queens. However, bumble bee workers were significantly
fewer in these locations later in the season, suggesting reduced colony success.
The median collection dates of workers of three bumble bee species were earlier
near canola fields, suggesting a dynamic response of colonies to the increased
floral resources. Different species experienced this shift to different extents.
The sweat bee was not affected by canola cultivation intensity. Our findings
suggest that mass-flowering crops such as canola are attractive to bumble bee
queens and therefore may lead to higher rates of colony establishment, but also
that colonies established near this crop may be less successful. We propose that
the effect on bumble bees can be mitigated by spacing the crop more evenly with
respect to alternate floral resources.
PMID- 28405305
TI - Metabolic costs of capital energy storage in a small-bodied ectotherm.
AB - Reproduction is energetically financed using strategies that fall along a
continuum from animals that rely on stored energy acquired prior to reproduction
(i.e., capital breeders) to those that rely on energy acquired during
reproduction (i.e., income breeders). Energy storage incurs a metabolic cost.
However, previous studies suggest that this cost may be minimal for small-bodied
ectotherms. Here I test this assumption. I use a laboratory feeding experiment
with the European green crab Carcinus maenas to establish individuals with
different amounts of energy storage. I then demonstrate that differences in
energy storage account for 26% of the variation in basal metabolic costs. The
magnitudes of these costs for any individual crab vary through time depending on
the amount of energy it has stored, as well as on temperature-dependent
metabolism. I use previously established relationships between temperature- and
mass-dependent metabolic rates, combined with a feasible annual pattern of energy
storage in the Gulf of Maine and annual sea surface temperature patterns in this
region, to estimate potential annual metabolic costs expected for mature female
green crabs. Results indicate that energy storage should incur an ~8% increase in
metabolic costs for female crabs, relative to a hypothetical crab that did not
store any energy. Translated into feeding, for a medium-sized mature female (45
mm carapace width), this requires the consumption of an additional ~156 mussels
annually to support the metabolic cost of energy storage. These results indicate,
contrary to previous assumptions, that the cost of energy storage for small
bodied ectotherms may represent a considerable portion of their basic operating
energy budget. An inability to meet these additional costs of energy storage may
help explain the recent decline of green crabs in the Gulf of Maine where reduced
prey availability and increased consumer competition have combined to hamper
green crab foraging success in recent years.
PMID- 28405306
TI - New aspects of grassland recovery in old-fields revealed by trait-based analyses
of perennial-crop-mediated succession.
AB - Classical old-field succession studies focused on vegetation changes after the
abandonment of annual croplands or on succession after the elimination of
cultivated crops. Perennial-crop-mediated succession, where fields are initially
covered by perennial crops, reveals alternative aspects of old-field succession
theories. We tested the validity of classical theories of old-field succession
for perennial-crop-mediated succession. We formulated the following hypotheses:
(1) functional diversity increases with increasing field age; (2) resource
acquisition versus conservation trade-off shifts toward conservation at community
level during the succession; (3) the importance of spatial and temporal seed
dispersal decreases during the succession; and (4) competitiveness and stress
tolerance increases and ruderality decreases at community level during the
succession. We studied functional diversity, trait distributions and plant
strategies in differently aged old-fields using chronosequence method. We found
increasing functional richness and functional divergence, but also unchanged or
decreasing functional evenness. We detected a shift from resource acquisition to
resource conservation strategy of communities during the succession. The role of
spatial and temporal seed dispersal was found to be important not only at the
initial but also at latter successional stages. We found an increasing stress
tolerance and a decreasing ruderality during succession, while the
competitiveness remained unchanged at the community level. Despite the markedly
different starting conditions, we found that classical and perennial-crop
mediated old-field successions have some similarities regarding the changes of
functional diversity, resource acquisition versus conservation trade-off, and
seed dispersal strategies. However, we revealed also the subsequent differences.
The competitive character of communities remained stable during the succession;
hence, the initial stages of perennial-crop-mediated succession can be similar to
the middle stages of classical old-field succession. Moreover, the occupied
functional niche space and differentiation were larger in the older stages, but
resources were not effectively utilized within this space, suggesting that the
stabilization of the vegetation requires more time.
PMID- 28405307
TI - The shift from plant-plant facilitation to competition under severe water deficit
is spatially explicit.
AB - The stress-gradient hypothesis predicts a higher frequency of facilitative
interactions as resource limitation increases. Under severe resource limitation,
it has been suggested that facilitation may revert to competition, and
identifying the presence as well as determining the magnitude of this shift is
important for predicting the effect of climate change on biodiversity and plant
community dynamics. In this study, we perform a meta-analysis to compare temporal
differences of species diversity and productivity under a nurse plant (Retama
sphaerocarpa) with varying annual rainfall quantity to test the effect of water
limitation on facilitation. Furthermore, we assess spatial differences in the
herbaceous community under nurse plants in situ during a year with below-average
rainfall. We found evidence that severe rainfall deficit reduced species
diversity and plant productivity under nurse plants relative to open areas. Our
results indicate that the switch from facilitation to competition in response to
rainfall quantity is nonlinear. The magnitude of this switch depended on the
aspect around the nurse plant. Hotter south aspects under nurse plants resulted
in negative effects on beneficiary species, while the north aspect still showed
facilitation. Combined, these results emphasize the importance of spatial
heterogeneity under nurse plants for mediating species loss under reduced
precipitation, as predicted by future climate change scenarios. However, the
decreased water availability expected under climate change will likely reduce
overall facilitation and limit the role of nurse plants as refugia, amplifying
biodiversity loss.
PMID- 28405308
TI - A gradient of nutrient enrichment reveals nonlinear impacts of fertilization on
Arctic plant diversity and ecosystem function.
AB - Rapid environmental change at high latitudes is predicted to greatly alter the
diversity, structure, and function of plant communities, resulting in changes in
the pools and fluxes of nutrients. In Arctic tundra, increased nitrogen (N) and
phosphorus (P) availability accompanying warming is known to impact plant
diversity and ecosystem function; however, to date, most studies examining Arctic
nutrient enrichment focus on the impact of relatively large (>25x estimated
naturally occurring N enrichment) doses of nutrients on plant community
composition and net primary productivity. To understand the impacts of Arctic
nutrient enrichment, we examined plant community composition and the capacity for
ecosystem function (net ecosystem exchange, ecosystem respiration, and gross
primary production) across a gradient of experimental N and P addition expected
to more closely approximate warming-induced fertilization. In addition, we
compared our measured ecosystem CO 2 flux data to a widely used Arctic ecosystem
exchange model to investigate the ability to predict the capacity for CO 2
exchange with nutrient addition. We observed declines in abundance-weighted plant
diversity at low levels of nutrient enrichment, but species richness and the
capacity for ecosystem carbon uptake did not change until the highest level of
fertilization. When we compared our measured data to the model, we found that the
model explained roughly 30%-50% of the variance in the observed data, depending
on the flux variable, and the relationship weakened at high levels of enrichment.
Our results suggest that while a relatively small amount of nutrient enrichment
impacts plant diversity, only relatively large levels of fertilization-over an
order of magnitude or more than warming-induced rates-significantly alter the
capacity for tundra CO 2 exchange. Overall, our findings highlight the value of
measuring and modeling the impacts of a nutrient enrichment gradient, as warming
related nutrient availability may impact ecosystems differently than single-level
fertilization experiments.
PMID- 28105318
TI - Validation of commercially available sphingosine kinase 2 antibodies for use in
immunoblotting, immunoprecipitation and immunofluorescence.
AB - Sphingosine kinase 2 (SK2) is a ubiquitously expressed lipid kinase that has
important, albeit complex and poorly understood, roles in regulating cell
survival and cell death. In addition to being able to promote cell cycle arrest
and apoptosis under certain conditions, it has recently been shown that SK2 can
promote neoplastic transformation and tumorigenesis in vivo. Therefore, well
validated and reliable tools are required to study and better understand the true
functions of SK2. Here, we compare two commercially available SK2 antibodies: a
rabbit polyclonal antibody from Proteintech that recognizes amino acids 266-618
of human SK2a, and a rabbit polyclonal antibody from ECM Biosciences that
recognizes amino acids 36-52 of human SK2a. We examine the performance of these
antibodies for use in immunoblotting, immunoprecipitation and immunofluorescence
staining of endogenous SK2, using human HEK293 and HeLa cell lines, as well as
mouse embryonic fibroblasts (MEFs). Furthermore, we assess the specificity of
these antibodies to the target protein through the use of siRNA-mediated SK2
knockdown and SK2 knockout ( Sphk2-/-) MEFs. Our results demonstrate that the
Proteintech anti-SK2 antibody reproducibly displayed superior sensitivity and
selectivity towards SK2 in immunoblot analyses, while the ECM Biosciences anti
SK2 antibody was reproducibly superior for SK2 immunoprecipitation and detection
by immunofluorescence staining. Notably, both antibodies produced non-specific
bands and staining in the MEFs, which was not observed with the human cell lines.
Therefore, we conclude that the Proteintech SK2 antibody is a valuable reagent
for use in immunoblot analyses, and the ECM Biosciences SK2 antibody is a useful
tool for SK2 immunoprecipitation and immunofluorescence staining, at least in the
human cell lines employed in this study.
PMID- 28299187
TI - Engaging high school students in neuroscience research -through an e-internship
program.
AB - In this article, we describe the design and implementation of an e-internship
program that BioScience Project offers high school students over the summer.
Project topics are in the areas of behavioral neuroscience and brain disorders.
All research, teaching, and communication is done online using open access
databases and webtools, a learning management system, and Google apps. Students
conduct all aspects of a research project from formulating a question to
collecting and analyzing the data, to presenting their results in the form of a
scientific poster. Results from a pilot study involving fifteen students indicate
that students are capable of successfully completing such a project, and benefit
both intellectually and professionally from participating in the e-internship
program.
PMID- 28163906
TI - An ELISA DYRK1A non-radioactive kinase assay suitable for the characterization of
inhibitors.
AB - The DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) gene
encodes a proline-directed Ser/Thr kinase. Elevated expression and/or altered
distribution of the kinase have been implicated in the neurological impairments
associated with Down syndrome (DS) and Alzheimer's disease (AD). Consequently,
DYRK1A inhibition has been of significant interest as a potential strategy for
therapeutic intervention of DS and AD. Many classes of novel inhibitors have been
described in the past decade. Although non-radioactive methods for analyzing
DYRK1A inhibition have been developed, methods employing radioactive tracers are
still commonly used for quantitative characterization of DYRK1A inhibitors. Here,
we present a non-radioactive ELISA assay based on the detection of DYRK1A
phosphorylated dynamin 1a fragment using a phosphorylation site-specific
antibody. The assay was verified by the use of two well-characterized DYRK1A
inhibitors, epigallocatechin gallate (EGCG) and harmine. The IC 50s for EGCG and
harmine determined by the ELISA method were found to be comparable to those
previously measured by radioactive tracing methods. Furthermore, we determined
the mode of inhibition for EGCG and harmine by a modification of the ELISA assay.
This assay confirms the mode of inhibition of EGCG (non-ATP-competitive) and
harmine (ATP-competitive), as previously determined. We conclude that the ELISA
platform demonstrated here is a viable alternative to the traditional radioactive
tracer assays for analyzing DYRK1A inhibitors.
PMID- 28405312
TI - Barriers and facilitators to infection control at a hospital in northern India: a
qualitative study.
AB - BACKGROUND: Hospital acquired infections occur at higher rates in low- and middle
income countries, like India, than in high-income countries. Effective
implementation of infection control practices is crucial to reducing the
transmission of hospital acquired infections at hospitals worldwide. Yet, no
comprehensive assessments of the barriers to sustained, successful implementation
of hospital interventions have been performed in Indian healthcare settings to
date. The Systems Engineering Initiative for Patient Safety (SEIPS) model
examines problems through the lens of interactions between people and systems. It
is a natural fit for investigating the behavioral and systematic components of
infection control practices. METHODS: We conducted a qualitative study to assess
the facilitators and barriers to infection control practices at a 1250 bed
tertiary care hospital in Haryana, northern India. Twenty semi-structured
interviews of nurses and physicians, selected by convenience sampling, were
conducted in English using an interview guide based on the SEIPS model. All
interview data was subsequently transcribed and coded for themes. RESULTS:
Person, task, and organizational level factors were the primary barriers and
facilitators to infection control at this hospital. Major barriers included a
high rate of nursing staff turnover, time spent training new staff, limitations
in language competency, and heavy clinical workloads. A well developed infection
control team and an institutional climate that prioritizes infection control were
major facilitators. CONCLUSIONS: Institutional support is critical to the
effective implementation of infection control practices. Prioritizing resources
to recruit and retain trained, experienced nursing staff is also essential.
PMID- 28405313
TI - Artificial rearing influences the morphology, permeability and redox state of the
gastrointestinal tract of low and normal birth weight piglets.
AB - BACKGROUND: In this study the physiological implications of artificial rearing
were investigated. Low (LBW) and normal birth weight (NBW) piglets were compared
as they might react differently to stressors caused by artificial rearing. In
total, 42 pairs of LBW and NBW piglets from 16 litters suckled the sow until d19
of age or were artificially reared starting at d3 until d19 of age. Blood and
tissue samples that were collected after euthanasia at 0, 3, 5, 8 and 19 d of
age. Histology, ELISA, and Ussing chamber analysis were used to study proximal
and distal small intestine histo-morphology, proliferation, apoptosis, tight
junction protein expression, and permeability. Furthermore, small intestine,
liver and systemic redox parameters (GSH, GSSG, GSH-Px and MDA) were investigated
using HPLC. RESULTS: LBW and NBW artificially reared piglets weighed respectively
40 and 33% more than LBW and NBW sow-reared piglets at d19 (P < 0.01).
Transferring piglets to a nursery at d3 resulted in villus atrophy, increased
intestinal FD-4 and HRP permeability and elevated GSSG/GSH ratio in the distal
small intestine at d5 (P < 0.05). GSH concentrations in the proximal small
intestine remained stable, while they decreased in the liver (P < 0.05). From d5
until d19, villus width and crypt depth increased, whereas PCNA, caspase-3,
occludin and claudin-3 protein expressions were reduced. GSH, GSSG and
permeability recovered in artificially reared piglets (P < 0.05). CONCLUSION: The
results suggest that artificial rearing altered the morphology, permeability and
redox state without compromising piglet performance. The observed effects were
not depending on birth weight.
PMID- 28405314
TI - Mitochondrial DNA T7719G in tRNA-Lys gene affects litter size in Small-tailed Han
sheep.
AB - BACKGROUND: In farm animals, mitochondrial DNA (mtDNA) effect on economic
performance remains hot-topic for breeding and genetic selection. Here, 53
maternal lineages of Small-tailed Han sheep were used to investigate the
association of mitochondrial DNA variations and the lambing litter size. RESULTS:
Sequence sweeping of the mitochondrial coding regions discovered 31 non
synonymous mutations, and the association study revealed that T7719G in mtDNA
tRNA-Lys gene was associated with litter size (P < 0.05), manifesting 0.29 lambs
per litter between the G and T carriers. Furthermore, using the mixed linear
model, we assayed the potential association of the ovine litter size and
haplogroups and multiple-level mtDNA haplotypes, including general haplotypes,
assembled haplotypes of electron transport chain contained sequences (H-ETC),
mitochondrial respiratory complex contained sequences (H-MRC) and mitochondrial
genes (H-gene, including polypeptide-coding genes, rRNA genes and tRNA genes).
The strategy for assembled mitochondrial haplotypes was proposed for the first
time in mtDNA association analyses on economic traits, although none of the
significant relations could be concluded (P > 0.05). In addition, the nuclear
major gene BMPR1B was significantly correlated with litter size in the flock (P <
0.05), however, did not interact with mtDNA T7719G mutation (P > 0.05).
CONCLUSIONS: Our results highlight mutations of ovine mitochondrial coding genes,
suggesting T7719G in tRNA-Lys gene be a potentially useful marker for selection
of sheep litter size.
PMID- 28405315
TI - Disappearance and appearance of an indigestible marker in feces from growing pigs
as affected by previous- and current-diet composition.
AB - BACKGROUND: Indigestible markers are commonly utilized in digestion studies, but
the complete disappearance or maximum appearance of a marker in feces can be
affected by diet composition, feed intake, or an animal's BW. The objectives of
this study were to determine the impact of previous (Phase 1, P1) and current-
(Phase 2, P2) diet composition on marker disappearance (Cr) and appearance (Ti)
in pigs fed 3 diets differing in NDF content. RESULTS: When pigs were maintained
on the 25.1, 72.5, and 125.0 g/kg NDF diets, it took 5.1, 4.1, and 2.5 d,
respectively, for Cr levels to decrease below the limit of quantitation; or 4.6,
3.7, or 2.8 d, respectively, for Ti to be maximized. These effects were not,
however, independent of the previous diet as indicated by the interaction between
P1 and P2 diets on fecal marker concentrations (P < 0.01). When dietary NDF
increased from P1 to P2, it took less time for fecal Cr to decrease or fecal Ti
to be maximized (an average of 2.5 d), than if NDF decreased from P1 to P2 where
it took longer for fecal Cr to decrease or fecal Ti to be maximized (an average
of 3.4 d). CONCLUSIONS: Because of the wide range in excretion times reported in
the literature and improved laboratory methods for elemental detection, the data
suggests that caution must be taken in considering dietary fiber concentrations
of the past and currently fed diets so that no previous dietary marker addition
remains in the digestive tract or feces such that a small amount of maker is
present to confound subsequent experimental results, and that marker
concentration have stabilized when these samples are collected.
PMID- 28405316
TI - Endoscopic techniques to detect small-bowel neuroendocrine tumors: A literature
review.
AB - BACKGROUND: The diagnosis of small-bowel neuroendocrine tumors (SbNETs) has
improved with the advent of video capsule endoscopy (CE) and double-balloon
enteroscopy (DBE). The data describing the efficacy of CE/DBE in the detection of
SbNETs are scanty. AIM: The aim of this article is to review the current evidence
on the role of DBE and CE in the diagnosis of SbNETs. MATERIAL AND METHODS: A
bibliographical search was performed in PubMed using the following keywords:
"neuroendocrine tumors and enteroscopy/and capsule endoscopy" and "small bowel
neuroendocrine tumors." RESULTS: CE and DBE can be complementary and show a
similar diagnostic yield. The number of false-negative results has not been
established yet because of the "work-up bias" observed in the majority of the
studies. CONCLUSIONS: DBE and CE appear to be both safe and effective procedures
useful in the diagnosis of SbNETs. Further studies are required to clarify their
potential complications and relationship with other techniques, particularly
nuclear imaging.
PMID- 28405317
TI - Changes in gene expression of neo-squamous mucosa after endoscopic treatment for
dysplastic Barrett's esophagus and intramucosal adenocarcinoma.
AB - BACKGROUND: Endoscopic therapy, including by radiofrequency ablation (RFA) or
endoscopic mucosal resection (EMR), is first line treatment for Barrett's
esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC) and
may be appropriate for some patients with low-grade dysplasia (LGD). OBJECTIVE:
The purpose of this study was to investigate the molecular effects of
endotherapy. METHODS: mRNA expression of 16 genes significantly associated with
different BE stages was measured in paired pre-treatment BE tissues and post
treatment neo-squamous biopsies from 36 patients treated by RFA (19 patients, 3
IMC, 4 HGD, 12 LGD) or EMR (17 patients, 4 IMC, 13 HGD). EMR was performed prior
to RFA in eight patients. Normal squamous esophageal tissues were from 20 control
individuals. RESULTS: Endoscopic therapy resulted in significant change towards
the normal squamous expression profile for all genes. The neo-squamous expression
profile was significantly different to the normal control profile for 11 of 16
genes. CONCLUSION: Endotherapy results in marked changes in mRNA expression, with
replacement of the disordered BE dysplasia or IMC profile with a more "normal"
profile. The neo-squamous mucosa was significantly different to the normal
control squamous mucosa for most genes. The significance of this finding is
uncertain but it may support continued endoscopic surveillance after successful
endotherapy.
PMID- 28405318
TI - Argon plasma coagulation compared with stent placement in the palliative
treatment of inoperable oesophageal cancer.
AB - BACKGROUND: Self-expandable metal stents (SEMSs) are the main palliative modality
used in inoperable oesophageal cancer. Other palliative modalities, including
argon plasma coagulation (APC), have also been used. OBJECTIVE: The purpose of
this study was to assess the relative efficacy of SEMS and APC regarding the
survival of patients with inoperable oesophageal cancer, not receiving
chemo/radiotherapy. METHODS: Single centre, retrospective analysis of all
patients (n = 228) with inoperable oesophageal cancer between January 2000 and
July 2014, not receiving chemo-radiotherapy, treated with SEMS (n = 160) or APC
(n = 68) as primary palliation modalities. Cox regression analysis was performed
to identify individual factors affecting survival and Kaplan-Meier curves were
created for patients treated with APC and SEMS for stage III and IV disease.
Survival intervals were compared by the log-rank test. RESULTS: Type of treatment
was the only statistically significant factor affecting survival, after disease
stage stratification (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.13
1.65 of SEMS over APC, p: 0.002). Median survival for patients treated with APC
and SEMS was 257 (interquartile range (IQR): 414, 124) and 151 (IQR: 241, 61)
days respectively in stage III disease. It was 135 (IQR: 238, 43) and 70 (IQR:
148, 32) days respectively in stage IV disease. Both differences were
statistically significant (p = 0.02 and 0.05 respectively). CONCLUSIONS: APC is a
promising palliation modality in inoperable oesophageal cancer, when patients are
not candidates for chemo-radiotherapy. A randomized controlled trial will be
needed to confirm those results.
PMID- 28405319
TI - Family history is an independent risk factor for the progression of gastric
atrophy among patients with Helicobacter pylori infection.
AB - BACKGROUND AND AIM: Risk factors for progression of gastric atrophy have not been
fully elucidated. The aim of this study was to evaluate the risk factors for the
development of atrophic gastritis in patients with Helicobacter pylori (H. pylori
) infection. METHODS: We reviewed 206 H. pylori-infected patients
retrospectively. Endoscopic gastric atrophy was classified into closed- and open
type. We conducted univariate and multivariate logistic regression analyses on
the contribution of age, sex, body mass index, past history of cancer, the first
degree family history of gastric cancer, habitual smoking and alcohol drinking,
and endoscopic findings of gastric ulcer or duodenal ulcer for open-type gastric
atrophy. RESULTS: On multivariate analysis, age (odds ratio = 1.079, 95%
confidence interval = 1.048-1.11, p < 0.001), family history of gastric cancer
(odds ratio = 3.967, 95% confidence interval = 1.414-10.6, p = 0.006) and
duodenal ulcer (odds ratio = 0.834, 95% confidence interval = 0.711-0.977, p =
0.024) were the factors independently associated with open-type gastric atrophy.
CONCLUSIONS: A first-degree family history of gastric cancer, absence of duodenal
ulcer, and old age were independent risk factors for the progression of gastric
atrophy among H. pylori-infected patients. Careful examination with upper
gastrointestinal endoscopy is necessary in patients with such risk factors.
PMID- 28405320
TI - Distinct metaplastic and inflammatory phenotypes in autoimmune and adenocarcinoma
associated chronic atrophic gastritis.
AB - BACKGROUND: Autoimmune gastritis (AIG) and adenocarcinoma-associated chronic
atrophic gastritis (CAG) are both associated with oxyntic atrophy, but AIG
patients demonstrate an increased risk of carcinoid tumors rather than the
elevated risk of adenocarcinoma observed with CAG. We therefore sought to compare
the characteristics of the metaplastic mucosa in AIG and CAG patients. METHODS:
We examined markers for metaplasia (spasmolytic polypeptide expressing metaplasia
(SPEM) and intestinal metaplasia) as well as proliferation (Ki67) and immune cell
populations (neutrophils, macrophages, and eosinophils) in gastric sections from
16 female patients with autoimmune thyroiditis and AIG and 17 patients with CAG
associated with gastric adenocarcinoma. RESULTS: Both AIG and CAG patients
demonstrated prominent SPEM and intestinal metaplasia. However, AIG patients
displayed significantly lower numbers of infiltrating macrophages and
significantly reduced mucosal cell proliferation as compared to CAG patients.
CONCLUSIONS: These findings indicate that, while both AIG and CAG patients
display prominent oxyntic atrophy and metaplasia, the AIG patients do not show
proliferative metaplastic lineages that would predispose to adenocarcinoma.
PMID- 28405321
TI - The expansion of endoscopic submucosal dissection in France: A prospective
nationwide survey.
AB - INTRODUCTION: Early reports of endoscopic submucosal dissection (ESD) in Europe
suggested high complication rates and disappointing outcomes compared to
publications from Japan. Since 2008, we have been conducting a nationwide survey
to monitor the outcomes and complications of ESD over time. MATERIAL AND METHODS:
All consecutive ESD cases from 14 centers in France were prospectively included
in the database. Demographic, procedural, outcome and follow-up data were
recorded. The results obtained over three years were compared to previously
published data covering the 2008-2010 period. RESULTS: Between November 2010 and
June 2013, 319 ESD cases performed in 314 patients (62% male, mean (+/-SD) age
65.4 +/- 12) were analyzed and compared to 188 ESD cases in 188 patients (61%
male, mean (+/-SD) age 64.6 +/- 13) performed between January 2008 and October
2010. The mean (+/-SD) lesion size was 39 +/- 12 mm in 2010-2013 vs 32.1 +/- 21
for 2008-2010 (p = 0.004). En bloc resection improved from 77.1% to 91.7% (p <
0.0001) while R0 en bloc resection remained stable from 72.9% to 71.9% (p = 0.8)
over time. Complication rate dropped from 29.2% between 2008 and 2010 to 14.1%
between 2010 and 2013 (p < 0.0001), with bleeding decreasing from 11.2% to 4.7%
(p = 0.01) and perforations from 18.1% to 8.1% (p = 0.002) over time. No
procedure-related mortality was recorded. CONCLUSIONS: In this multicenter study,
ESD achieved high rates of en bloc resection with a significant trend toward
better outcomes over time. Improvements in lesion delineation and
characterization are still needed to increase R0 resection rates.
PMID- 28405322
TI - Specific dyspeptic symptoms are associated with poor response to therapy in
patients with gastroesophageal reflux disease.
AB - INTRODUCTION: In patients with gastroesophageal reflux disease (GORD), co
existence of functional dyspepsia (FD) is known to be associated with poor
response to proton pump inhibitors (PPIs), but the contribution of specific
dyspepsia symptoms has not yet been systematically investigated. OBJECTIVE: We
aimed to characterize the impact of dyspepsia symptoms on response to PPIs in
patients with GORD. METHODS: The enrolled subjects were consecutive patients with
a diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on
PPI therapy. Patients were divided into two groups, refractory and responders,
according to the persistence of GORD symptoms. A standardized questionnaire for
FD was also administered to assess presence of dyspepsia symptoms. RESULTS: In
the subgroup of refractory patients FD was more prevalent than in responders,
with post-prandial fullness, nausea, vomiting, early satiation and epigastric
pain being significantly prevalent in refractory GORD patients. In the
multivariate analysis only early satiation and vomiting were significantly
associated with poor response to PPIs. CONCLUSION: Co-existence of FD is
associated with refractory GORD. We showed that only early satiation and vomiting
are risk factors for poor response to therapy with PPIs. Our findings suggest
that symptoms of early satiation and vomiting would help to identify the subset
of PPI-refractory GORD patients.
PMID- 28405323
TI - The use of enteral access for continuous delivery of levodopa-carbidopa in
patients with advanced Parkinson's disease.
AB - BACKGROUND: Continuous delivery to the jejunum of levodopa-carbidopa is a
promising therapy in patients with advanced Parkinson's disease, as it reduces
motor fluctuation. Percutaneous endoscopic gastrostomy and jejunal tube (PEG-J)
placement is a suitable option for this. However, studies focused in PEG-J
management are lacking. OBJECTIVES: We report our experience regarding this
technique, including technical success, adverse events and outcomes, in patients
with advanced Parkinson's disease. METHODS: Twenty-seven advanced Parkinson's
disease patients (17 men, median age: 64 years, median disease duration: 11
years) were included in a retrospective study from June 2007 to April 2015. The
median follow-up period was 48 months (1-96). RESULTS: No adverse events were
noted during and after nasojejunal tube insertion (to assess treatment efficacy).
After a good therapeutic response, a PEG-J was placed successfully in all
patients. The PEG tube was inserted according to Ponsky's method. The jejunal
extension was inserted during the same procedure in all patients. Twelve patients
(44%) experienced severe adverse events related to the PEG-J insertion, which
occurred after a median follow-up of 15.5 months. Endoscopy was the main
treatment modality. Patients who experienced severe adverse events had a higher
comorbidity score (p = 0.011) but were not older (p = 0.941) than patients who
did not. CONCLUSIONS: While all patients responded well to levodopa-carbidopa
regarding neurological outcomes, gastro-intestinal severe adverse events were
frequent and related to comorbidities. Endoscopic treatment is the cornerstone
for management of PEG-J related events. In conclusion, clinicians and
endoscopists, as well as patients, should be fully informed of procedure-related
adverse events and patients should be followed in centres experienced in their
management.
PMID- 28405324
TI - 25-OH vitamin D level has no impact on the efficacy of antiviral therapy in naive
genotype 1 HCV-infected patients.
AB - BACKGROUND AND AIM: The impact of 25-OH vitamin D on sustained viral response
(SVR) to antiviral therapy and on fibrosis progression in hepatitis C is debated.
We assessed the impact of 25-OH vitamin D concentration on the efficacy of
antiviral therapy in naive genotype 1 hepatitis C virus (HCV)-infected patients.
METHODS: The study population consisted of treatment-naive genotype 1 patients
enrolled in a randomised controlled trial. A total of 516 patients received
peginterferon alpha-2a 180 ug/week plus ribavirin 800 mg/day for 24 weeks. There
were 349 patients with undetectable HCV RNA (<50 IU/ml) at week 24 (W24) who were
randomised to continue dual therapy (n = 173) or to continue peginterferon alone
(n = 176) until week 48. 25-OH vitamin D concentration was measured at baseline
in frozen serum. RESULTS: A total of 461 patients could be analysed for virologic
response at W24, and 285 (119 non-responders at W24 + 166 responders who
continued dual therapy until W48) for the impact of SVR. There were 487 patients
who could be analysed for fibrosis progression. Metavir fibrosis scores
(centralised analysis) were: F1 30%, F2 34%, F3 27% and F4 9%. Median 25-OH
vitamin D concentrations were similar in virologic responders (13.5 ng/ml) and in
non-responders at W24 (12.6 ng/ml), as well as in patients with SVR (12.8 ng/ml)
and without SVR (12.8 ng/ml, 3.99) at W72. Median 25-OH vitamin D concentrations
were: F1: 14.30 ng/ml, F2: 13.50 ng/ml, F3: 13.30 ng/ml and F4: 12.80 ng/ml.
CONCLUSION: In this study, 25-OH vitamin D level has no impact on the efficacy of
antiviral therapy in naive genotype 1 HCV-infected patients.
PMID- 28405325
TI - Controlled attenuation parameter using the FibroScan(r) XL probe for
quantification of hepatic steatosis for non-alcoholic fatty liver disease in an
Asian population.
AB - BACKGROUND: The FibroScan(r) XL probe reduces failure of liver stiffness
measurement (LSM) and unreliable results in obese patients. OBJECTIVE: The
objective of this article is to evaluate the accuracy of controlled attenuation
parameter (CAP) obtained using the XL probe for the estimation of hepatic
steatosis in patients with non-alcoholic fatty liver disease (NAFLD). METHODS:
Adult NAFLD patients with a liver biopsy within six months were included and were
examined with the FibroScan(r) M and XL probes. Histopathological findings were
reported according to the Non-Alcoholic Steatohepatitis Clinical Research Network
Scoring System. Participants who did not have fatty liver on ultrasonography were
recruited as controls. RESULTS: A total of 57 NAFLD patients and 22 controls were
included. The mean age of the NAFLD patients and controls was 50.1 +/- 10.4 years
and 20.2 +/- 1.3 years, respectively (p = 0.000). The mean body mass index was
30.2 +/- 5.0 kg per m2 and 20.5 +/- 2.4 kg per m2, respectively (p = 0.000). The
distribution of steatosis grades were: S0, 29%; S1, 17%; S2, 35%; S3, 19%. The
AUROC for estimation of steatosis grade >= S1, S2 and S3 was 0.94, 0.80 and 0.69,
respectively, using the M probe, and 0.97, 0.81 and 0.67, respectively, using the
XL probe. CONCLUSION: CAP obtained using the XL probe had similar accuracy as the
M probe for the estimation of hepatic steatosis in NAFLD patients.
PMID- 28405326
TI - Von Willebrand factor and alkaline phosphatase predict re-transplantation-free
survival after the first liver transplantation.
AB - BACKGROUND: After liver transplantation (LT), there are liver-related, infectious
and cardiovascular complications that contribute to reduced graft survival. These
conditions are associated with an increase in the Von Willebrand factor antigen
(VWF-Ag), which was previously correlated with survival in cirrhotic patients.
OBJECTIVE: Evaluate VWF-Ag as a predictive marker of re-transplantation-free
survival in patients after LT. METHODS: We measured VWF-Ag in patients after
first LT and then followed them prospectively with regard to the primary
endpoint, namely re-transplantation-free survival. RESULTS: There were 6 out of
80 patients who died or received re-LT during follow-up. In these patients, the
median VWF-Ag was 510.6%, which was significantly higher (p = 0.001) than in the
patients who were alive at the end of follow-up (with a median VWF-Ag = 186.8%).
At a cut-off of 286.8%, VWF-Ag was significantly correlated with re
transplantation-free survival (p < 0.001). VWF-Ag was independently associated
with re-transplantation-free survival in a multivariate analysis; as was alkaline
phosphatase (ALP), but not the model of end-stage liver disease (MELD) score,
donor age, nor cold ischemia time. A score combining VWF-Ag and ALP showed an
impressive capability in the receiver operating characteristic (ROC) analysis
(with area under the curve (AUC) = 0.958) to distinguish between patients with
regard to the primary endpoint. CONCLUSIONS: VWF-Ag is a non-invasive marker that
can predict outcome in patients after LT. Its diagnostic performance increased
when combined with ALP in a newly developed scoring system.
PMID- 28405327
TI - Iron overload correlates with serum liver fibrotic markers and liver dysfunction:
Potential new methods to predict iron overload-related liver fibrosis in
thalassemia patients.
AB - BACKGROUND: Early detection of liver fibrosis in thalassemia patients and rapid
initiation of treatment to interfere with its progression are extremely
important. OBJECTIVE: This study aimed to find a sensitive, easy-to-detect and
noninvasive method other than liver biopsy for early detection of liver fibrosis
in thalassemia patients. METHODS: A total of 244 Chinese Thalassemia patients
with non-transfusion-dependent thalassemia (NTDT, n = 105) or thalassemia major
(TM, n = 139) and 120 healthy individuals were recruited into the present study,
and blood collagen type IV (C IV), precollagen type III (PIIINPC) and hyaluronic
acid (HA), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
ferritin were measured. Liver iron concentration was determined by MRI. The
correlation of serum markers with liver iron load and liver function was
evaluated. RESULTS: Serum C IV, PIIINPC and HA were significantly elevated in
Chinese patients with NTDT and further elevated in TM patients. Moreover, C IV,
PIIINPC and HA were also positively correlated to serum ferritin and liver iron
concentration and further elevated during the progression to multi-organ damage
in NTDT patients. Finally, serum ferritin and liver iron concentration were
significantly correlated with liver dysfunction determined by AST and ALT.
CONCLUSION: Taken together, our results indicate that monitoring serum C IV,
PIIINPC and HA is a potentially sensitive method to predict the risks for iron
overload-related liver fibrosis in Chinese thalassemia patients.
PMID- 28405328
TI - Photodynamic therapy with polyhematoporphyrin for malignant biliary obstruction:
A nationwide retrospective study of 150 consecutive applications.
AB - BACKGROUND: Photodynamic therapy (PDT) is a palliative treatment for malignant
biliary obstruction. OBJECTIVE: The objective of this article is to assess the
feasibility and safety of this technique. METHODS: In this nationwide,
retrospective study of prospectively collected clinical data, all patients
treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013
were included. Feasibility, adverse events, stent patency and mortality rates
were investigated. RESULTS: Eighty-eight patients (54 male, 34 female, median age
69 years) underwent 150 PDT procedures at seven Austrian referral centers for
biliary endoscopy. The predominant underlying disease was Klatskin tumor (79/88).
All PDT procedures were feasible without technical issues. Cholangitis was the
most frequent adverse event (21/88). Stent patency was 246 days (95% CI 203-289)
median and was significantly longer for metal than for plastic stents (269 vs. 62
days, p < 0.01). The median survival was 12.4 months (95% CI 9.7-14.9 m)
calculated from first PDT and 15.6 months (95% CI 12.3-18.7 m) calculated from
initial diagnosis. In patients suffering from biliary tract cancer, Cox
regression revealed the number of PDT treatment sessions as the only independent
predictor of survival at a multivariate analysis (p = 0.048). CONCLUSION: PDT
using polyhematoporphyrin was feasible and safe in this nationwide analysis.
Survival data suggest a benefit of PDT in this unselected real-life patient
population. Prospective trials comparing PDT to other palliative treatments will
help to define its role in the management of malignant biliary obstruction. The
study is registered at ClinicalTrials.gov number: NCT02504957.
PMID- 28405329
TI - The impact of prophylactic pancreatic stenting on post-ERCP pancreatitis: A
nationwide, register-based study.
AB - BACKGROUND AND OBJECTIVES: The role of prophylactic pancreatic stenting (PS) in
preventing post-endoscopic retrograde cholangio-pancreatography (ERCP)
pancreatitis (PEP) has yet to be determined. Most previous studies show
beneficial effects in reducing PEP when prophylactic pancreatic stents are used,
especially in high-risk ERCP procedures. The present study aimed to address the
use of PS in a nationwide register-based study in which the primary outcome was
the prophylactic effect of PS in reducing PEP. METHODS: All ERCP-procedures
registered in the nationwide Swedish Registry for Gallstone Surgery and ERCP
(GallRiks) between 2006 and 2014 were studied. The primary outcome was PEP but we
also studied other peri- and postoperative complication rates. RESULTS: Data from
43,595 ERCP procedures were analyzed. In the subgroup of patients who received PS
with a total diameter <= 5 Fr, the risk of PEP increased nearly four times
compared to those who received PS with a total diameter of >5 Fr (OR 3.58; 95% CI
1.40-11.07). Furthermore, patients who received PS of >5 Fr and >5 cm had a
significantly lower pancreatitis frequency compared to those with shorter stents
of the same diameter (1.39% vs 15.79%; p = 0.0033). CONCLUSIONS: PS with a
diameter of >5 Fr and a length of >5 cm seems to have a better protective effect
against PEP, compared to shorter and thinner stents. However, in the present
version of GallRiks it is not possible to differentiate the exact type of
pancreatic stent (apart from material, length and diameter) that has been
introduced, so our conclusion must be interpreted with caution.
PMID- 28405331
TI - Gradual stiffness versus magnetic imaging-guided variable stiffness colonoscopes:
A randomized noninferiority trial.
AB - BACKGROUND: Colonoscopes with gradual stiffness have recently been developed to
enhance cecal intubation. OBJECTIVE: We aimed to determine if the performance of
gradual stiffness colonoscopes is noninferior to that of magnetic endoscopic
imaging (MEI)-guided variable stiffness colonoscopes. METHODS: Consecutive
patients were randomized to screening colonoscopy with Fujifilm gradual stiffness
or Olympus MEI-guided variable stiffness colonoscopes. The primary endpoint was
cecal intubation rate (noninferiority limit 5%). Secondary endpoints included
cecal intubation time. We estimated absolute risk differences with 95% confidence
intervals (CIs). RESULTS: We enrolled 475 patients: 222 randomized to the gradual
stiffness instrument, and 253 to the MEI-guided variable stiffness instrument.
Cecal intubation rate was 91.7% in the gradual stiffness group versus 95.6% in
the variable stiffness group. The adjusted absolute risk for cecal intubation
failure was 4.3% higher in the gradual stiffness group than in the variable
stiffness group (upper CI border 8.1%). Median cecal intubation time was 13
minutes in the gradual stiffness group and 10 minutes in the variable stiffness
group (p < 0.001). CONCLUSIONS: The study is inconclusive with regard to
noninferiority because the 95% CI for the difference in cecal intubation rate
between the groups crosses the noninferiority margin. (ClinicalTrials.gov
identifier: NCT01895504).
PMID- 28405330
TI - Middle-term mortality and re-bleeding after initial diverticular bleeding: A
nationwide study of 365 mostly elderly French patients.
AB - BACKGROUND AND AIMS: The aim of this study was to determine the mortality and re
bleeding rates, and the risk factors involved, in a cohort of patients with
previous diverticular bleeding (DB). METHODS: In 2007, data on 2462 patients with
lower gastrointestinal (GI) bleeding were collected prospectively at several
French hospitals. We studied the follow-up of patients with DB retrospectively.
The following data were collected: age, mortality rates and re-bleeding rates,
drug intake, surgery and comorbidities. RESULTS: Data on 365 patients, including
181 women (mean age 83.6 +/- 9.8 years) were available. The median follow-up time
was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among
the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and
three underwent surgical procedures. Anticoagulation and antiplatelet therapy was
discontinued in 70 cases (19.2%). The independent risk factors contributing to
mortality were age > 80 years (HR = 3.18 (2.1-4.9); p < 0.001) and a Charlson
comorbidity score > 2 (1.91 (1.31-2.79); p = 0.003). Discontinuation of therapy
was not significantly associated with a risk of death due to cardiovascular
events. No risk factors responsible for re-bleeding were identified, such as
antiplatelet and anticoagulant therapy in particular. CONCLUSIONS: In this
cohort, the rates of mortality and DB re-bleeding after a median follow-up time
of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths
recorded were not due to re-bleeding.
PMID- 28405333
TI - Potential celiac disease in Indian patients.
PMID- 28405332
TI - Association between diverticulosis and colonic neoplastic lesions in individuals
with a positive faecal immunochemical test.
AB - BACKGROUND: The association between diverticulosis and colonic neoplastic lesions
has been suggested, but data in literature are conflicting. This study aimed to
investigate such a relationship in patients participating in a colorectal cancer
screening program who underwent high-quality colonoscopy. METHODS: Data from
consecutive individuals 50-75 years of age with a positive faecal immunological
test were considered. Diverticulosis was categorised as present or absent. The
prevalence of neoplastic lesions (adenoma, advanced adenoma, and cancer) between
individuals with and those without diverticula was compared. A multivariate
analysis was performed. RESULTS: Overall, data from 970 consecutive individuals
were evaluated, and diverticulosis was detected in 354 (36.5%) cases. At least
one adenoma was detected in 490 (50.5%) people, at least one advanced adenoma in
264 (27.2%), multiple adenoma in 71 (7.3%), whilst a cancer was diagnosed in 48
(4.9%) cases. At univariate analysis, the adenoma detection rate in patients with
diverticula was significantly higher than in controls (55.9% vs 47.4%; p =
0.011). At multivariate analysis, presence of diverticulosis was an independent
risk factor for both adenoma detection rate (OR = 1.58; 95% CI = 1.14-2.18; p =
0.006) and advanced adenoma (OR = 1.57; 95% CI = 1.10-2.24; p = 0.013), but not
for colorectal cancer. CONCLUSIONS: In a colorectal screening setting, the
adenoma detection rate was significantly higher in individuals with
diverticulosis than in controls.
PMID- 28405334
TI - Potential celiac disease in Indian patients: Response.
PMID- 28405335
TI - Young GI Angle: How to apply for a grant.
PMID- 28405336
TI - European Digestive Health Summit: experts call for improved promotion of
prevention and treatment methods for gastrointestinal diseases across the
continent.
PMID- 28405337
TI - Autoimmune hemolytic anemia associated with babesiosis.
AB - BACKGROUND: Babesiosis is endemic in selected areas in North America. Babesia
infection is commonly associated with anemia, thrombocytopenia, hyponatremia and
elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused
by parasitic and viral infections but has not been well characterized. CASE
PRESENTATION: We describe two cases diagnosed with babesiosis triggering severe
AIHA. One case had history of splenectomy, and the other was an elderly patient.
Older, immunocompromised and asplenic patients may be particularly at risk for
post-babesiosis AIHA (PB-AIHA). CONCLUSIONS: The pathogenesis for conventional
AIHA and PB-AIHA appears to be different, since splenectomy is a treatment for
conventional AIHA, whereas PB-AIHA is seen more often in asplenic patients.
Further investigation into this intriguing mechanism of host immune response to
babesiosis may help to elucidate the overall mechanism of infection- triggered
AIHA.
PMID- 28405338
TI - What we have changed our minds about: Part 2. Borderline personality disorder,
epistemic trust and the developmental significance of social communication.
AB - In Part 1 of this paper, we discussed emerging evidence suggesting that a general
psychopathology or 'p' factor underlying the various forms of psychopathology
should be conceptualized in terms of the absence of resilience, that is, the
absence of positive reappraisal mechanisms when faced with adversity. These
impairments in the capacity for positive reappraisal seem to provide a
comprehensive explanation for the association between the p factor and
comorbidity, future caseness, and the 'hard-to-reach' character of many patients
with severe personality pathology, most notably borderline personality disorder
(BPD). In this, the second part of the paper, we trace the development of the
absence of resilience to disruptions in the emergence of human social
communication, based on recent evolutionary and developmental psychopathology
accounts. We argue that BPD and related disorders may be reconceptualized as a
form of social understanding in which epistemic hypervigilance, distrust or
outright epistemic freezing is an adaptive consequence of the social learning
environment. Negative appraisal mechanisms become overriding, particularly in
situations of attachment stress. This constitutes a shift towards a more socially
oriented perspective on personality psychopathology in which the absence of
psychological resilience is seen as a learned response to the transmission of
social knowledge. This shift in our views has also forced us to reconsider the
role of attachment in BPD. The implications for prevention and intervention of
this novel approach are discussed.
PMID- 28405339
TI - Ethiopian patients' perceptions of anti-diabetic medications: implications for
diabetes education.
AB - BACKGROUND: The purpose of this study is to explore medication-related
perceptions of adult patients with type 2 diabetes attending treatment in public
hospitals of urban centers in central Ethiopia. METHODS: Qualitative in-depth
interviews were held with 39 participants selected to represent a range of
treatment experiences and socio-demographic characteristics who were attending
their treatment in 3 public hospitals. Interviews continued until key themes were
saturated. The interview and analysis was guided by Horne's necessity-concerns
model. RESULTS: The findings revealed medication-related perceptions some of
which were similar to those of Western patients and others that seem to be
informed by local socio-cultural contexts. Participants' perceptions focused on
the necessity of and concerns about their anti-diabetic medications, giving more
emphasis to the latter. Concerns were expressed about both perceived and
experienced adverse effects, inconveniences in handling the medications and
access. It was evident that some of these concerns were exaggerated but could
nevertheless negatively affect adherence to prescribed medications including
resistance to initiate insulin with potential impact on health outcomes.
CONCLUSIONS: Understanding patients' perceptions of their medications is critical
for developing a diabetes education program that considers local contexts and
beliefs to enhance adherence. Education programs should consider patients'
concerns about medication adverse effects and reasons for use so as to improve
their adherence and health outcomes.
PMID- 28405340
TI - Association of physiological and psychological health outcomes with physical
activity and sedentary behavior in adults with type 2 diabetes.
AB - PURPOSE: To examine the association between change in moderate-to-vigorous
physical activity (MVPA) and sedentary behavior (SB) over a 6-month period with
physiological and psychological factors in adults with type 2 diabetes (T2D).
METHODS: Participants included 26 middle-aged (mean age=56.1+/-10.8 years; 42%
women), overweight/obese (mean body mass index (BMI) =37.22+/-8.78 kg/m2) adults
who had been diagnosed with T2D within the past 5 years (mean HbA1c=7.81%).
Participants underwent a physical examination, blood tests, and psychological
questionnaires, including a self-report questionnaire that assessed the
consumption of high glycemic and low glycemic load foods. Participants wore an
Actigraph accelerometer for 7 days to assess MVPA and SB. All measures were
collected at baseline and at the 6-month follow-up. Spearman rank correlations
and regression models were conducted to examine the relationship between activity
variables, and the association of activity measures with health outcomes at the 6
month follow-up. RESULTS: Decreases in duration of SB bouts and increases in MVPA
were associated with decreased levels of HbA1c (p<0.05). Over 50% of the variance
in HbA1c levels could be attributed to changes in MVPA and SB. CONCLUSIONS: MVPA
and SB were independently associated with diabetes-related health outcomes.
Results suggest that emphasis should be placed on increasing MVPA while
decreasing SB, particularly duration of SB bouts. This suggests that even small
changes in daily behavior may contribute to improvement in diabetes-related
health outcomes.
PMID- 28405341
TI - Diabetes incidence and glucose intolerance prevalence increase with higher
outdoor temperature.
AB - OBJECTIVE: Rising global temperatures might contribute to the current worldwide
diabetes epidemic, as higher ambient temperature can negatively impact glucose
metabolism via a reduction in brown adipose tissue activity. Therefore, we
examined the association between outdoor temperature and diabetes incidence in
the USA as well as the prevalence of glucose intolerance worldwide. RESEARCH
DESIGN AND METHODS: Using meta-regression, we determined the association between
mean annual temperature and diabetes incidence during 1996-2009 for each US state
separately. Subsequently, results were pooled in a meta-analysis. On a global
scale, we performed a meta-regression analysis to assess the association between
mean annual temperature and the prevalence of glucose intolerance. RESULTS: We
demonstrated that, on average, per 1 degrees C increase in temperature, age
adjusted diabetes incidence increased with 0.314 (95% CI 0.194 to 0.434) per
1000. Similarly, the worldwide prevalence of glucose intolerance increased by
0.170% (95% CI 0.107% to 0.234%) per 1 degrees C rise in temperature. These
associations persisted after adjustment for obesity. CONCLUSIONS: Our findings
indicate that the diabetes incidence rate in the USA and prevalence of glucose
intolerance worldwide increase with higher outdoor temperature.
PMID- 28405342
TI - Association between secondhand smoke and obesity and glucose abnormalities: data
from the National Health and Nutrition Examination Survey (NHANES 1999-2010).
AB - OBJECTIVE: The objective of this study is to investigate the relationship between
cotinine level-confirmed secondhand smoke (SHS) exposure and glycemic parameters
and obesity. RESEARCH DESIGN AND METHODS: We examined a cohort of 6472 adults
from the National Health and Nutrition Examination Surveys, 1999-2010. Serum
cotinine levels and self-reported data on smoking were used to determine smoking
status. The outcome variables were body mass index (BMI) and glycemic status
(HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and
fasting plasma glucose (FPG). Descriptive, bivariate, and multivariate analyses
were conducted. RESULTS: Using cotinine level-confirmed smoking status, 1794
(27.4%) of the sample were current smokers, 1681 (25.0%) were former smokers,
1158 (17.8%) were secondhand smokers, and 1839 (29.8%) were non-smokers. In a
generalized linear model after controlling for potential confounding variables,
secondhand smokers had higher adjusted levels of HOMA-IR, FPG, and BMI compared
with non-smokers (p<0.05). Adjustment for BMI demonstrated that some, but not
all, of the detrimental effects of SHS on glycemic parameters are mediated by the
increased body weight of secondhand smokers. CONCLUSIONS: We conclude that SHS is
associated with obesity and worsening glycemic parameters. More studies are
needed to show a causal relationship between SHS and glycemic parameters and to
understand the mechanisms involved in the association.
PMID- 28405343
TI - Role of depression in diabetes management in an ethnic minority population: a
case of Korean Americans with type 2 diabetes.
AB - BACKGROUND: Comorbid depression and diabetes mellitus (DM) compound challenges to
disease management such as low health literacy, insufficient access to care, and
social or linguistic isolation. Korean Americans (KAs), predominantly first
generation immigrants, suffer from a high prevalence of type 2 DM and depression.
Limited research on KAs has prevented the development of effective interventions.
OBJECTIVES: To compare the prevalence of depression in KAs with DM and all
Americans with/without DM, and to explore correlates of comorbid DM and
depression and strategies to address KAs' DM and depression. METHODS: KAs' data
were from a clinical trial of a community-based self-help intervention to improve
KAs' DM and mental health outcomes. National Health and Nutrition Examination
Survey data sets enabled comparison. Clinical indicators included hemoglobin A1C,
lipid panel, and body mass index. Psychobehavioral indicators included self
efficacy for DM management, quality of life, and depression (Patient Health
Questionnaire-9 (PHQ-9)). RESULTS: More KAs with DM had depression (44.2%) than
did all Americans with DM (28.7%) or without DM (20.1%). Significantly more KAs
with DM had mild (29.3%) or clinical (14.9%) depression than did Americans with
DM (mild, 17.2%; clinical, 11.5%) or without (mild, 13.8%; clinical, 6.3%). One
of six KAs with DM (16.9%) thought of suicide or self-harm (Americans
with/without =5.0%, 2.8%). The self-help intervention reduced the mean PHQ-9 from
5.4 at baseline to 4.1 at 12 months. LIMITATIONS: External validity might be
limited; KAs' data were from one study site. CONCLUSIONS: The prevalence of
depression and DM among KAs warrants the development of efficacious
interventions. TRIAL REGISTRATION NUMBER: NCT01264796.
PMID- 28405344
TI - Successful long-term weight loss among participants with diabetes receiving an
intervention promoting an adapted Mediterranean-style dietary pattern: the Heart
Healthy Lenoir Project.
AB - OBJECTIVE: To examine weight change by diabetes status among participants
receiving a Mediterranean-style diet, physical activity, and weight loss
intervention adapted for delivery in the southeastern USA, where rates of
cardiovascular disease (CVD) are disproportionately high. RESEARCH DESIGN AND
METHODS: The intervention included: Phase I (months 1-6), an individually
tailored intervention promoting a Mediterranean-style dietary pattern and
increased walking; Phase II (months 7-12), option of a 16-week weight loss
intervention for those with BMI>=25 kg/m2 offered as 16 weekly group sessions or
5 group sessions and 10 phone calls, or a lifestyle maintenance intervention; and
Phase III (months 13-24), weight loss maintenance intervention for those losing
>=8 pounds with all others receiving a lifestyle maintenance intervention. Weight
change was assessed at 6, 12, and 24-month follow-up. RESULTS: Baseline
characteristics (n=339): mean age 56, 77% female, 65% African-American, 124 (37%)
with diabetes; mean weight 103 kg for those with diabetes and 95 kg for those
without. Among participants with diabetes, average weight change was -1.2 kg (95%
CI -2.1 to -0.4) at 6 months (n=92), -1.5 kg (95% CI -2.9 to -0.2) at 12 months
(n=96), and -3.7 kg (95% CI -5.2 to -2.1) at 24 months (n=93). Among those
without diabetes, weight change was -0.4 kg (95% CI -1.4 to 0.6) at 24 months
(n=154). CONCLUSIONS: Participants with diabetes experienced sustained weight
loss at 24-month follow-up. High-risk US populations with diabetes may experience
clinically important weight loss from this type of lifestyle intervention. TRIAL
REGISTRATION NUMBER: NCT01433484.
PMID- 28405345
TI - Lower glycemic load meals reduce diurnal glycemic oscillations in women with risk
factors for gestational diabetes.
AB - OBJECTIVE: Maternal glycemia plays a key role in fetal growth. We hypothesized
that lower glycemic load (GL) meals (lower glycemic index, modestly lower
carbohydrate) would substantially reduce day-long glucose variability in women at
risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A
crossover study of 17 women (mean+/-SD age 34.8+/-4 years; gestational weeks
29.3+/-1.3; body mass index 23.8+/-4.7 kg/m2) who consumed a low GL or a high GL
diet in random order, 1-day each, over 2 consecutive days. Diets were energy
matched and fiber-matched with 5 meals per 24 hours. All food was provided.
Continuous glucose monitoring was used to assess diurnal glycemia. RESULTS:
Maternal glucose levels were 51% lower on the low GL day with lower incremental
area under the curve (iAUC+/-SEM 549+/-109 vs 1120+/-198 mmol/L min, p=0.015).
Glycemic variability was significantly lower on the low GL day, as demonstrated
by a lower average SD (0.7+/-0.1 vs 0.9+/-0.1, p<0.001) and lower mean amplitude
of glycemic excursions (2.1+/-0.2 vs 2.7+/-0.2 mmol/L, p<0.001). CONCLUSIONS: A
lower GL meal plan in pregnancy acutely halves day-long maternal glucose levels
and reduces glucose variability, providing further evidence to support the
utility of a low GL diet in pregnancy.
PMID- 28405346
TI - Safety and efficacy of saxagliptin for glycemic control in non-critically ill
hospitalized patients.
AB - OBJECTIVE: To evaluate whether saxagliptin is non-inferior to basal-bolus insulin
therapy for glycemic control in patients with controlled type 2 diabetes mellitus
(T2DM) admitted to hospital with non-critical illnesses. RESEARCH DESIGN AND
METHODS: This was an open-label, randomized controlled clinical trial. Patients
received either saxagliptin or basal-bolus insulin, both with correctional
insulin doses. The main study outcome was the mean daily blood glucose (BG) after
the first day of randomization. RESULTS: Of 66 patients completing the study, 33
(age 69+/-10 years, 40% men) were randomized to saxagliptin and 33 (age 67+/-10
years, 52% men) to basal-bolus insulin therapy. The mean daily BG was 149.8+/
22.0 mg/dL in the saxagliptin group and 146.9+/-30.5 mg/dL in the insulin group
(p=0.59). With an observed group difference of 2.9 mg/dL and an a priori margin
of 20 mg/dL, inferiority of saxagliptin was rejected in favor of non-inferiority
(p=0.007). There was no significant difference in the percentage of high or low
BG values. The insulin group received a higher number of insulin injections
(2.3+/-1.7/day vs 1.2+/-1.9/day; p<0.001) as well as a higher daily insulin dose
(13.3+/-12.9 units/day vs 2.4+/-3.3 units/day; p<0.001) than did the saxagliptin
group. Continuous BG monitoring showed that glycemic variability was lower in the
saxagliptin group as compared to the insulin group. Patient satisfaction scores
were similar in the two groups. CONCLUSIONS: We conclude that saxagliptin use is
non-inferior to basal-bolus insulin in non-critically ill hospitalized patients
with T2DM controlled on 0-2 oral agents without insulin. Saxagliptin use may
decrease glycemic variability in these patients. TRIAL REGISTRATION NUMBER:
NCT02182895.
PMID- 28405348
TI - Mental status assessment of disaster relief personnel by vocal affect display
based on voice emotion recognition.
AB - BACKGROUND: Disaster relief personnel tend to be exposed to excessive stress,
which can be a cause of mental disorders. To prevent from mental disorders,
frequent assessment of mental status is important. This pilot study aimed to
examine feasibility of stress assessment using vocal affect display (VAD) indices
as calculated by our proposed algorithms in a situation of comparison between
different durations of stay in stricken area as disaster relief operation, which
is an environment highly likely to induce stress. METHODS: We used Sensibility
Technology (ST) software to analyze VAD from voices of participants exposed to
extreme stress for either long or short durations, and we proposed algorithms for
indices of low VAD (VAD-L), high VAD (VAD-H), and VAD ratio (VAD-R), calculated
from the intensity of emotions as measured by voice emotion analysis. As a
preliminary validation, 12 members of Japan Self-Defense Forces dispatched
overseas for long (3 months or more) or short (about a week) durations were asked
to record their voices saying 11 phrases repeatedly across 6 days during their
dispatch. RESULTS: In the validation, the two groups showed an inverse
relationship in VAD-L and VAD-H, in that long durations in disaster zones
resulted in higher values of both VAD-L and VAD-R, and lower values of VAD-H,
compared with short durations. Interestingly, phrases produced varied results in
terms of group differences and VAD indices, demonstrating the sensitivity of the
ST. CONCLUSIONS: A comparison of the values obtained for the different groups of
subjects clarified that there were tendencies of the VAD-L, VAD-H, and VAD-R
indices observed for each group of participants. The results suggest the
possibility of using ST software in the measurement of affective aspects related
to mental health from vocal behavior.
PMID- 28405349
TI - Is there a standard for surgical therapy of hepatocellular carcinoma in healthy
and cirrhotic liver? A comparison of eight guidelines.
AB - BACKGROUND AND AIMS: Liver resection (LR) and transplantation are the most
reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare
different guidelines regarding indication for resection and transplantation
because of HCC with and without underlying cirrhosis. METHODS: We compared the
following guidelines published after 1 January 2010: American (American
Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola
de Oncologia Medica (SEOM)), European (European Association for the study of
liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and
European Society for Medical Oncology-European Society of Digestive Oncology
(ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)),
Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana
Oncologia Medica (AIOM)) and German (S3) guidelines. RESULTS: All guidelines
recommend resection as therapy of choice in healthy liver. Guidelines based on
the Barcelona Clinic Liver Cancer staging system recommend resection for single
HCC<2 cm and Child-Pugh A cirrhosis and for HCC<=5 cm with normal bilirubin and
portal pressure, whereas transplantation is recommended for multiple tumours
between Milan criteria and for single tumours <=5 cm and advanced liver
dysfunction. Patients with HCC and Child-Pugh C cirrhosis are not candidates for
transplantation. JSH guidelines recommend LR for patients with Child-Pugh A/B
with HCC without tumour size restriction; APASL guidelines in general exclude
patients with Child-Pugh A from transplantation. In patients with Child-Pugh B,
transplantation is the second-line therapy, if resection is not possible for
patients within Milan criteria. German and Italian guidelines recommend
transplantation for all patients within Milan criteria. CONCLUSIONS: Whereas
resection is the standard therapy of HCC in healthy liver, a standard regarding
the indication for LR and transplantation for HCC in cirrhotic liver does not
exist, although nearly all guidelines claim to be evidence based. Surprisingly,
despite European guidelines, Germany and Italy use their own national guidelines
which partially differ from the European. Possible solutions of the problems are
discussed.
PMID- 28405350
TI - Quantifying the energy stores of capital breeding humpback whales and income
breeding sperm whales using historical whaling records.
AB - Cetacean energy stores are known to vary according to life history, reproductive
status and time of year; however, the opportunity to quantify these relationships
is rare. Using a unique set of historical whaling records from Western Australia
(1952-1963), we investigated energy stores of large cetaceans with differing life
histories, and quantified the relationship between total body lipid and length
for humpback whales (Megaptera novaeangliae) (n = 905) and sperm whales (Physeter
macrocephalus) (n = 1961). We found that total body lipid increased with body
length in both humpback and sperm whales, consistent with size-related energy
stores. Male humpback whales stored 2.49 kl (15.6 barrels) (31.9-74.9%) more
lipid than male sperm whales of equivalent length, to fuel their annual
migration. Relative lipid stores of sperm whales (males) were constant throughout
the year, while those of humpback whales varied with reproductive class and
sampling date. Pregnant female humpback whales had higher relative energy stores
than non-pregnant females and males (26.2% and 37.4%, respectively), to fuel the
energy demands of gestation and lactation. Those that reached the sampling site
later (en route to their breeding grounds) carried higher lipid stores than those
that arrived earlier, possibly reflecting individual variation in residency times
in the Antarctic feeding grounds. Importantly, longer pregnant females had
relatively larger energy stores than the shorter pregnant females, indicating
that the smaller individuals may experience higher levels of energetic stress
during the migration fast. The relationships we developed between body lipid and
length can be used to inform bioenergetics and ecosystem models when such
detailed information is not available.
PMID- 28405347
TI - Friedreich Ataxia: current status and future prospects.
AB - Friedreich ataxia (FA) represents the most frequent type of inherited ataxia.
Most patients carry homozygous GAA expansions in the first intron of the frataxin
gene on chromosome 9. Due to epigenetic alterations, frataxin expression is
significantly reduced. Frataxin is a mitochondrial protein. Its deficiency leads
to mitochondrial iron overload, defective energy supply and generation of
reactive oxygen species. This review gives an overview over clinical and genetic
aspects of FA and discusses current concepts of frataxin biogenesis and function
as well as new therapeutic strategies.
PMID- 28405351
TI - Kea show no evidence of inequity aversion.
AB - It has been suggested that inequity aversion is a mechanism that evolved in
humans to maximize the pay-offs from engaging in cooperative tasks and to foster
long-term cooperative relationships between unrelated individuals. In support of
this, evidence of inequity aversion in nonhuman animals has typically been found
in species that, like humans, live in complex social groups and demonstrate
cooperative behaviours. We examined inequity aversion in the kea (Nestor
notabilis), which lives in social groups but does not appear to demonstrate wild
cooperative behaviours, using a classic token exchange paradigm. We compared the
number of successful exchanges and the number of abandoned trials in each
condition and found no evidence of an aversion to inequitable outcomes when there
was a difference between reward quality or working effort required between actor
and partner. We also found no evidence of inequity aversion when the subject
received no reward while their partner received a low-value reward.
PMID- 28405352
TI - Modelling human perception processes in pedestrian dynamics: a hybrid approach.
AB - In this paper, we present a hybrid mathematical model describing crowd dynamics.
More specifically, our approach is based on the well-established Helbing-like
discrete model, where each pedestrian is individually represented as a
dimensionless point and set to move in order to reach a target destination, with
deviations deriving from both physical and social forces. In particular, physical
forces account for interpersonal collisions, whereas social components include
the individual desire to remain sufficiently far from other walkers (the so
called territorial effect). In this respect, the repulsive behaviour of
pedestrians is here set to be different from traditional Helbing-like methods, as
it is assumed to be largely determined by how they perceive the presence and the
position of neighbouring individuals, i.e. either objectively as
pointwise/localized entities or subjectively as spatially distributed masses. The
resulting modelling environment is then applied to specific scenarios, that first
reproduce a real-world experiment, specifically designed to derive our model
hypothesis. Sets of numerical realizations are also run to analyse in more
details the pedestrian paths resulting from different types of perception of
small groups of static individuals. Finally, analytical investigations formalize
and validate from a mathematical point of view selected simulation outcomes.
PMID- 28405353
TI - Effects of 25 mg oxazepam on emotional mimicry and empathy for pain: a randomized
controlled experiment.
AB - Emotional mimicry and empathy are mechanisms underlying social interaction.
Benzodiazepines have been proposed to inhibit empathy and promote antisocial
behaviour. First, we aimed to investigate the effects of oxazepam on emotional
mimicry and empathy for pain, and second, we aimed to investigate the association
of personality traits to emotional mimicry and empathy. Participants (n=76) were
randomized to 25 mg oxazepam or placebo. Emotional mimicry was examined using
video clips with emotional expressions. Empathy was investigated by pain
stimulating the participant and a confederate. We recorded self-rated experience,
activity in major zygomatic and superciliary corrugator muscles, skin
conductance, and heart rate. In the mimicry experiment, oxazepam inhibited
corrugator activity. In the empathy experiment, oxazepam caused increased self
rated unpleasantness and skin conductance. However, oxazepam specifically
inhibited neither emotional mimicry nor empathy for pain. Responses in both
experiments were associated with self-rated empathic, psychopathic and
alexithymic traits. The present results do not support a specific effect of 25 mg
oxazepam on emotional mimicry or empathy.
PMID- 28405355
TI - Face familiarity promotes stable identity recognition: exploring face perception
using serial dependence.
AB - Studies suggest that familiar faces are processed in a manner distinct from
unfamiliar faces and that familiarity with a face confers an advantage in
identity recognition. Our visual system seems to capitalize on experience to
build stable face representations that are impervious to variation in retinal
input that may occur due to changes in lighting, viewpoint, viewing distance, eye
movements, etc. Emerging evidence also suggests that our visual system maintains
a continuous perception of a face's identity from one moment to the next despite
the retinal input variations through serial dependence. This study investigates
whether interactions occur between face familiarity and serial dependence. In two
experiments, participants used a continuous scale to rate attractiveness of
unfamiliar and familiar faces (either experimentally learned or famous) presented
in rapid sequences. Both experiments revealed robust inter-trial effects in which
attractiveness ratings for a given face depended on the preceding face's
attractiveness. This inter-trial attractiveness effect was most pronounced for
unfamiliar faces. Indeed, when participants were familiar with a given face,
attractiveness ratings showed significantly less serial dependence. These results
represent the first evidence that familiar faces can resist the temporal
integration seen in sequential dependencies and highlight the importance of
familiarity to visual cognition.
PMID- 28405356
TI - Nonlinear growth: an origin of hub organization in complex networks.
AB - Many real-world networks contain highly connected nodes called hubs. Hubs are
often crucial for network function and spreading dynamics. However, classical
models of how hubs originate during network development unrealistically assume
that new nodes attain information about the connectivity (for example the degree)
of existing nodes. Here, we introduce hub formation through nonlinear growth
where the number of nodes generated at each stage increases over time and new
nodes form connections independent of target node features. Our model reproduces
variation in number of connections, hub occurrence time, and rich-club
organization of networks ranging from protein-protein, neuronal and fibre tract
brain networks to airline networks. Moreover, nonlinear growth gives a more
generic representation of these networks compared with previous preferential
attachment or duplication-divergence models. Overall, hub creation through
nonlinear network expansion can serve as a benchmark model for studying the
development of many real-world networks.
PMID- 28405354
TI - The interpretation of mu suppression as an index of mirror neuron activity: past,
present and future.
AB - Mu suppression studies have been widely used to infer the activity of the human
mirror neuron system (MNS) in a number of processes, ranging from action
understanding, language, empathy and the development of autism spectrum disorders
(ASDs). Although mu suppression is enjoying a resurgence of interest, it has a
long history. This review aimed to revisit mu's past, and examine its recent use
to investigate MNS involvement in language, social processes and ASDs. Mu
suppression studies have largely failed to produce robust evidence for the role
of the MNS in these domains. Several key potential shortcomings with the use and
interpretation of mu suppression, documented in the older literature and
highlighted by more recent reports, are explored here.
PMID- 28405357
TI - Nonlinear amplitude dynamics in flagellar beating.
AB - The physical basis of flagellar and ciliary beating is a major problem in biology
which is still far from completely understood. The fundamental cytoskeleton
structure of cilia and flagella is the axoneme, a cylindrical array of
microtubule doublets connected by passive cross-linkers and dynein motor
proteins. The complex interplay of these elements leads to the generation of self
organized bending waves. Although many mathematical models have been proposed to
understand this process, few attempts have been made to assess the role of
dyneins on the nonlinear nature of the axoneme. Here, we investigate the
nonlinear dynamics of flagella by considering an axonemal sliding control
mechanism for dynein activity. This approach unveils the nonlinear selection of
the oscillation amplitudes, which are typically either missed or prescribed in
mathematical models. The explicit set of nonlinear equations are derived and
solved numerically. Our analysis reveals the spatio-temporal dynamics of dynein
populations and flagellum shape for different regimes of motor activity, medium
viscosity and flagellum elasticity. Unstable modes saturate via the coupling of
dynein kinetics and flagellum shape without the need of invoking a nonlinear
axonemal response. Hence, our work reveals a novel mechanism for the saturation
of unstable modes in axonemal beating.
PMID- 28405358
TI - Integrating multiple technologies to understand the foraging behaviour of
Hawaiian monk seals.
AB - The objective of this research was to investigate and describe the foraging
behaviour of monk seals in the main Hawaiian Islands. Specifically, our goal was
to identify a metric to classify foraging behaviour from telemetry instruments.
We deployed accelerometers, seal-mounted cameras and GPS tags on six monk seals
during 2012-2014 on the islands of Molokai, Kauai and Oahu. We used pitch,
calculated from the accelerometer, to identify search events and thus classify
foraging dives. A search event and consequent 'foraging dive' occurred when the
pitch was greater than or equal to 70 degrees at a depth less than or equal to
3 m. By integrating data from the accelerometers with video and GPS, we were able
to ground-truth this classification method and identify environmental variables
associated with each foraging dive. We used Bayesian logistic regression to
identify the variables that influenced search events. Dive depth, body motion
(mean overall dynamic body acceleration during the dive) and proximity to the sea
floor were the best predictors of search events for these seals. Search events
typically occurred on long, deep dives, with more time spent at the bottom (more
than 50% bottom time). We can now identify where monk seals are foraging in the
main Hawaiian Islands (MHI) and what covariates influence foraging behaviour in
this region. This increased understanding will inform management strategies and
supplement outreach and recovery efforts.
PMID- 28405359
TI - Suicides on the Austrian railway network: hotspot analysis and effect of
proximity to psychiatric institutions.
AB - Railway suicide is a significant public health problem. In addition to the loss
of lives, these suicides occur in public space, causing traumatization among
train drivers and passengers, and significant public transport delays. Prevention
efforts depend upon accurate knowledge of clustering phenomena across the railway
network, and spatial risk factors. Factors such as proximity to psychiatric
institutions have been discussed to impact on railway suicides, but analytic
evaluations are scarce and limited. We identify 15 hotspots on the Austrian
railway system while taking case location uncertainties into account. These
hotspots represent 0.9% of the total track length (5916 km/3676 miles) that
account for up to 17% of all railway suicides (N=1130). We model suicide
locations on the network using a smoothed inhomogeneous Poisson process and
validate it using randomization tests. We find that the density of psychiatric
beds is a significant predictor of railway suicide. Further predictors are
population density, multitrack structure and-less consistently-spatial socio
economic factors including total suicide rates. We evaluate the model for the
identified hotspots and show that the actual influence of these variables differs
across individual hotspots. This analysis provides important information for
suicide prevention research and practice. We recommend structural separation of
railway tracks from nearby psychiatric institutions to prevent railway suicide.
PMID- 28405360
TI - Towards an integrated food safety surveillance system: a simulation study to
explore the potential of combining genomic and epidemiological metadata.
AB - Foodborne infection is a result of exposure to complex, dynamic food systems. The
efficiency of foodborne infection is driven by ongoing shifts in genetic
machinery. Next-generation sequencing technologies can provide high-fidelity data
about the genetics of a pathogen. However, food safety surveillance systems do
not currently provide similar high-fidelity epidemiological metadata to associate
with genetic data. As a consequence, it is rarely possible to transform genetic
data into actionable knowledge that can be used to genuinely inform risk
assessment or prevent outbreaks. Big data approaches are touted as a revolution
in decision support, and pose a potentially attractive method for closing the gap
between the fidelity of genetic and epidemiological metadata for food safety
surveillance. We therefore developed a simple food chain model to investigate the
potential benefits of combining 'big' data sources, including both genetic and
high-fidelity epidemiological metadata. Our results suggest that, as for any
surveillance system, the collected data must be relevant and characterize the
important dynamics of a system if we are to properly understand risk: this
suggests the need to carefully consider data curation, rather than the more
ambitious claims of big data proponents that unstructured and unrelated data
sources can be combined to generate consistent insight. Of interest is that the
biggest influencers of foodborne infection risk were contamination load and
processing temperature, not genotype. This suggests that understanding food chain
dynamics would probably more effectively generate insight into foodborne risk
than prescribing the hazard in ever more detail in terms of genotype.
PMID- 28405361
TI - The geometry of structural equilibrium.
AB - Building on a long tradition from Maxwell, Rankine, Klein and others, this paper
puts forward a geometrical description of structural equilibrium which contains a
procedure for the graphic analysis of stress resultants within general three
dimensional frames. The method is a natural generalization of Rankine's
reciprocal diagrams for three-dimensional trusses. The vertices and edges of dual
abstract 4-polytopes are embedded within dual four-dimensional vector spaces,
wherein the oriented area of generalized polygons give all six components (axial
and shear forces with torsion and bending moments) of the stress resultants. The
relevant quantities may be readily calculated using four-dimensional Clifford
algebra. As well as giving access to frame analysis and design, the description
resolves a number of long-standing problems with the incompleteness of Rankine's
description of three-dimensional trusses. Examples are given of how the procedure
may be applied to structures of engineering interest, including an outline of a
two-stage procedure for addressing the equilibrium of loaded gridshell rooves.
PMID- 28405362
TI - Challenges and opportunities associated with waste management in India.
AB - India faces major environmental challenges associated with waste generation and
inadequate waste collection, transport, treatment and disposal. Current systems
in India cannot cope with the volumes of waste generated by an increasing urban
population, and this impacts on the environment and public health. The challenges
and barriers are significant, but so are the opportunities. This paper reports on
an international seminar on 'Sustainable solid waste management for cities:
opportunities in South Asian Association for Regional Cooperation (SAARC)
countries' organized by the Council of Scientific and Industrial Research
National Environmental Engineering Research Institute and the Royal Society. A
priority is to move from reliance on waste dumps that offer no environmental
protection, to waste management systems that retain useful resources within the
economy. Waste segregation at source and use of specialized waste processing
facilities to separate recyclable materials has a key role. Disposal of residual
waste after extraction of material resources needs engineered landfill sites
and/or investment in waste-to-energy facilities. The potential for energy
generation from landfill via methane extraction or thermal treatment is a major
opportunity, but a key barrier is the shortage of qualified engineers and
environmental professionals with the experience to deliver improved waste
management systems in India.
PMID- 28405363
TI - An experimental study of the putative mechanism of a synthetic autonomous rotary
DNA nanomotor.
AB - DNA has been used to construct a wide variety of nanoscale molecular devices.
Inspiration for such synthetic molecular machines is frequently drawn from
protein motors, which are naturally occurring and ubiquitous. However, despite
the fact that rotary motors such as ATP synthase and the bacterial flagellar
motor play extremely important roles in nature, very few rotary devices have been
constructed using DNA. This paper describes an experimental study of the putative
mechanism of a rotary DNA nanomotor, which is based on strand displacement, the
phenomenon that powers many synthetic linear DNA motors. Unlike other examples of
rotary DNA machines, the device described here is designed to be capable of
autonomous operation after it is triggered. The experimental results are
consistent with operation of the motor as expected, and future work on an
enhanced motor design may allow rotation to be observed at the single-molecule
level. The rotary motor concept presented here has potential applications in
molecular processing, DNA computing, biosensing and photonics.
PMID- 28405364
TI - East African origins for Madagascan chickens as indicated by mitochondrial DNA.
AB - The colonization of Madagascar by Austronesian-speaking people during AD 50-500
represents the most westerly point of the greatest diaspora in prehistory. A
range of economically important plants and animals may have accompanied the
Austronesians. Domestic chickens (Gallus gallus) are found in Madagascar, but it
is unclear how they arrived there. Did they accompany the initial Austronesian
speaking populations that reached Madagascar via the Indian Ocean or were they
late arrivals with Arabian and African sea-farers? To address this question, we
investigated the mitochondrial DNA control region diversity of modern chickens
sampled from around the Indian Ocean rim (Southeast Asia, South Asia, the Arabian
Peninsula, East Africa and Madagascar). In contrast to the linguistic and human
genetic evidence indicating dual African and Southeast Asian ancestry of the
Malagasy people, we find that chickens in Madagascar only share a common ancestor
with East Africa, which together are genetically closer to South Asian chickens
than to those in Southeast Asia. This suggests that the earliest expansion of
Austronesian-speaking people across the Indian Ocean did not successfully
introduce chickens to Madagascar. Our results further demonstrate the complexity
of the translocation history of introduced domesticates in Madagascar.
PMID- 28405365
TI - Dynamics of host populations affected by the emerging fungal pathogen
Batrachochytrium salamandrivorans.
AB - Emerging infectious diseases cause extirpation of wildlife populations. We use an
epidemiological model to explore the effects of a recently emerged disease caused
by the salamander-killing chytrid fungus Batrachochytrium salamandrivorans (Bsal)
on host populations, and to evaluate which mitigation measures are most likely to
succeed. As individuals do not recover from Bsal, we used a model with the states
susceptible, latent and infectious, and parametrized the model using data on host
and pathogen taken from the literature and expert opinion. The model suggested
that disease outbreaks can occur at very low host densities (one female per
hectare). This density is far lower than host densities in the wild. Therefore,
all naturally occurring populations are at risk. Bsal can lead to the local
extirpation of the host population within a few months. Disease outbreaks are
likely to fade out quickly. A spatial variant of the model showed that the
pathogen could potentially spread rapidly. As disease mitigation during outbreaks
is unlikely to be successful, control efforts should focus on preventing disease
emergence and transmission between populations. Thus, this emerging wildlife
disease is best controlled through prevention rather than subsequent actions.
PMID- 28405366
TI - Processing political misinformation: comprehending the Trump phenomenon.
AB - This study investigated the cognitive processing of true and false political
information. Specifically, it examined the impact of source credibility on the
assessment of veracity when information comes from a polarizing source
(Experiment 1), and effectiveness of explanations when they come from one's own
political party or an opposition party (Experiment 2). These experiments were
conducted prior to the 2016 Presidential election. Participants rated their
belief in factual and incorrect statements that President Trump made on the
campaign trail; facts were subsequently affirmed and misinformation retracted.
Participants then re-rated their belief immediately or after a delay. Experiment
1 found that (i) if information was attributed to Trump, Republican supporters of
Trump believed it more than if it was presented without attribution, whereas the
opposite was true for Democrats and (ii) although Trump supporters reduced their
belief in misinformation items following a correction, they did not change their
voting preferences. Experiment 2 revealed that the explanation's source had
relatively little impact, and belief updating was more influenced by perceived
credibility of the individual initially purporting the information. These
findings suggest that people use political figures as a heuristic to guide
evaluation of what is true or false, yet do not necessarily insist on veracity as
a prerequisite for supporting political candidates.
PMID- 28405367
TI - Shifts in rotifer life history in response to stable isotope enrichment: testing
theories of isotope effects on organismal growth.
AB - In ecology, stable isotope labelling is commonly used for tracing material
transfer in trophic interactions, nutrient budgets and biogeochemical processes.
The main assumption in this approach is that the enrichment with a heavy isotope
has no effect on the organism growth and metabolism. This assumption is, however,
challenged by theoretical considerations and experimental studies on kinetic
isotope effects in vivo. Here, I demonstrate profound changes in life histories
of the rotifer Brachionus plicatilis fed 15N-enriched algae (0.4-5.0 at%); i.e.
at the enrichment levels commonly used in ecological studies. These findings
support theoretically predicted effects of heavy isotope enrichment on growth,
metabolism and ageing in biological systems and underline the importance of
accounting for such effects when using stable isotope labelling in experimental
studies.
PMID- 28405368
TI - Concurrence in the ability for lipid synthesis between life stages in insects.
AB - The ability to synthesize lipids is critical for an organism's fitness; hence,
metabolic pathways, underlying lipid synthesis, tend to be highly conserved.
Surprisingly, the majority of parasitoids deviate from this general metabolic
model by lacking the ability to convert sugars and other carbohydrates into
lipids. These insects spend the first part of their life feeding and developing
in or on an arthropod host, during which they can carry over a substantial amount
of lipid reserves. While many parasitoid species have been tested for lipogenic
ability at the adult life stage, it has remained unclear whether parasitoid
larvae can synthesize lipids. Here we investigate whether or not several insects
can synthesize lipids during the larval stage using three ectoparasitic wasps
(developing on the outside of the host) and the vinegar fly Drosophila
melanogaster that differ in lipogenic ability in the adult life stage. Using
feeding experiments and stable isotope tracing with gas chromatography/mass
spectrometry, we first confirm lipogenic abilities in the adult life stage. Using
topical application of stable isotopes in developing larvae, we then provide
clear evidence of concurrence in lipogenic ability between larval and adult life
stages in all species tested.
PMID- 28405369
TI - Game-based situation awareness training for child and adult cyclists.
AB - Safe cycling requires situation awareness (SA), which is the basis for
recognizing and anticipating hazards. Children have poorer SA than adults, which
may put them at risk. This study investigates whether cyclists' SA can be trained
with a video-based learning game. The effect of executive working memory on SA
was also studied. Thirty-six children (9-10 years) and 22 adults (21-48 years)
played the game. The game had 30 video clips filmed from a cyclist's perspective.
Each clip was suddenly masked and two or three locations were presented. The
player's task was to choose locations with a potential hazard and feedback was
given for their answers. Working memory capacity (WMC) was tested with a counting
span task. Children's and adults' performance improved while playing the game,
which suggests that playing the game trains SA. Adults performed better than
children, and they also glanced at hazards more while the video was playing.
Children expectedly had a lower WMC than adults, but WMC did not predict
performance within the groups. This indicates that SA does not depend on WMC when
passively viewing videos.
PMID- 28405370
TI - Changeable camouflage: how well can flounder resemble the colour and spatial
scale of substrates in their natural habitats?
AB - Flounder change colour and pattern for camouflage. We used a spectrometer to
measure reflectance spectra and a digital camera to capture body patterns of two
flounder species camouflaged on four natural backgrounds of different spatial
scale (sand, small gravel, large gravel and rocks). We quantified the degree of
spectral match between flounder and background relative to the situation of
perfect camouflage in which flounder and background were assumed to have
identical spectral distribution. Computations were carried out for three
biologically relevant observers: monochromatic squid, dichromatic crab and
trichromatic guitarfish. Our computations present a new approach to analysing
datasets with multiple spectra that have large variance. Furthermore, to
investigate the spatial match between flounder and background, images of flounder
patterns were analysed using a custom program originally developed to study
cuttlefish camouflage. Our results show that all flounder and background spectra
fall within the same colour gamut and that, in terms of different observer visual
systems, flounder matched most substrates in luminance and colour contrast.
Flounder matched the spatial scales of all substrates except for rocks. We
discuss findings in terms of flounder biology; furthermore, we discuss our
methodology in light of hyperspectral technologies that combine high-resolution
spectral and spatial imaging.
PMID- 28405371
TI - Scrounging by foragers can resolve the paradox of enrichment.
AB - Theoretical models of predator-prey systems predict that sufficient enrichment of
prey can generate large amplitude limit cycles, paradoxically causing a high risk
of extinction (the paradox of enrichment). Although real ecological communities
contain many gregarious species, whose foraging behaviour should be influenced by
socially transmitted information, few theoretical studies have examined the
possibility that social foraging might resolve this paradox. I considered a
predator population in which individuals play the producer-scrounger foraging
game in one-prey-one-predator and two-prey-one-predator systems. I analysed the
stability of a coexisting equilibrium point in the one-prey system and that of
non-equilibrium dynamics in the two-prey system. The results revealed that social
foraging could stabilize both systems, and thereby resolve the paradox of
enrichment when scrounging behaviour (i.e. kleptoparasitism) is prevalent in
predators. This suggests a previously neglected mechanism underlying a powerful
effect of group-living animals on the sustainability of ecological communities.
PMID- 28405372
TI - Putative sex-specific human pheromones do not affect gender perception,
attractiveness ratings or unfaithfulness judgements of opposite sex faces.
AB - Debate continues over the existence of human sex pheromones. Two substances,
androstadienone (AND) and estratetraenol (EST), were recently reported to signal
male and female gender, respectively, potentially qualifying them as human sex
pheromones. If AND and EST truly signal gender, then they should affect
reproductively relevant behaviours such as mate perception. To test this
hypothesis, heterosexual, Caucasian human participants completed two computer
based tasks twice, on two consecutive days, exposed to a control scent on one day
and a putative pheromone (AND or EST) on the other. In the first task, 46
participants (24 male, 22 female) indicated the gender (male or female) of five
gender-neutral facial morphs. Exposure to AND or EST had no effect on gender
perception. In the second task, 94 participants (43 male, 51 female) rated
photographs of opposite-sex faces for attractiveness and probable sexual
unfaithfulness. Exposure to the putative pheromones had no effect on either
attractiveness or unfaithfulness ratings. These results are consistent with those
of other experimental studies and reviews that suggest AND and EST are unlikely
to be human pheromones. The double-blind nature of the current study lends
increased support to this conclusion. If human sex pheromones affect our
judgements of gender, attractiveness or unfaithfulness from faces, they are
unlikely to be AND or EST.
PMID- 28405373
TI - Bioinspired polymer microstructures for directional transport of oily liquids.
AB - Nature has always served as an inspiration for scientists, helping them to solve
a large diversity of technical problems. In our case, we are interested in the
directional transport of oily liquids and as a model for this application we used
the flat bug Dysodius lunatus. In this report, we present arrays of drops looking
like polymer microstructures produced by the two-photon polymerization technique
that mimic the micro-ornamentation from the bug's cuticle. A good directionality
of oil transport was achieved, directly controlled by the direction of the
pointed microstructures at the surface. If the tips of the drop-like
microstructures are pointing towards the left side, the liquid front moves to the
right and vice versa. Similar effects could be expected for the transport of oily
lubricants. These results could, therefore, be interesting for applications in
friction and wear reduction.
PMID- 28405374
TI - Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral
(Corallium rubrum).
AB - Sexual reproduction is widespread among eukaryotes, and the sex-determining
processes vary greatly among species. While genetic sex determination (GSD) has
been intensively described in bilaterian species, no example has yet been
recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD
among multicellular species suggests that similar evolutionary forces can promote
this system, and that these forces could occur also in non-bilaterians. Studying
sex determination across the range of Metazoan diversity is indeed important to
understand better the evolution of this mechanism and its lability. We tested the
existence of sex-linked genes in the gonochoric red coral (Corallium rubrum,
Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461
single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations
including 53 that were morphologically sexed. We found a strong association
between the allele frequencies of 472 SNPs and the sex of individuals, suggesting
an XX/XY sex-determination system. This result was confirmed by the
identification of 435 male-specific loci. An independent test confirmed that the
amplification of these loci enabled us to identify males with absolute certainty.
This is the first demonstration of a GSD system among non-bilaterian species and
a new example of its convergence in multicellular eukaryotes.
PMID- 28405375
TI - A modified 'NanoSuit(r)' preserves wet samples in high vacuum: direct
observations on cells and tissues in field-emission scanning electron microscopy.
AB - Although field-emission scanning electron microscopy (FE-SEM) has proven very
useful in biomedical research, the high vacuum required (10-3 to 10-7 Pa)
precludes direct observations of living cells and tissues at high resolution and
often produces unwanted structural changes. We have previously described a method
that allows the investigator to keep a variety of insect larvae alive in the high
vacuum environment of the electron microscope by encasing the organisms in a
thin, vacuum-proof suit, the 'NanoSuit(r)'. However, it was impossible to protect
wet tissues freshly excised from intact organisms or cultured cells. Here we
describe an improved 'NanoSuit' technique to overcome this limitation. We
protected the specimens with a surface shield enhancer (SSE) solution that
consists of glycerine and electrolytes and found that the fine structure of the
SSE-treated specimens is superior to that of conventionally prepared specimens.
The SSE-based NanoSuit affords a much stronger barrier to gas and/or liquid loss
than the previous NanoSuit did and, since it allows more detailed images, it
could significantly help to elucidate the 'real' organization of cells and their
functions.
PMID- 28405376
TI - A test of male infanticide as a reproductive tactic in a cichlid fish.
AB - Infanticide and offspring cannibalism are taxonomically widespread phenomena. In
some group-living species, a new dominant individual taking over a group can
benefit from infanticide if doing so induces potential mates to become
reproductively available sooner. Despite widespread observations of infanticide
(i.e. egg cannibalism) among fishes, no study has investigated whether egg
cannibalism occurs in fishes as a result of group takeovers, or how this type of
cannibalism might be adaptive. Using the cooperatively breeding cichlid,
Neolamprologus pulcher, we tested whether new unrelated males entering the
dominant position in a social group were more likely to cannibalize eggs, and
whether such cannibalism would shorten the interval until the female's next
spawning. Females spawned again sooner if their broods were removed than if they
were cared for. Egg cannibalism occurred frequently after a group takeover event,
and was rarer if the original male remained with the group. While dominant
breeder females were initially highly aggressive towards newcomer males that took
over the group, the degree of resistance depended on relative body size
differences between the new pair and, ultimately, female aggression did not
prevent egg cannibalism. Egg cannibalism, however, did not shorten the duration
until subsequent spawning, or increase fecundity during subsequent breeding in
our laboratory setting. Our results show that infanticide as mediated through
group takeovers is a taxonomically widespread behaviour.
PMID- 28405377
TI - Modulation of leg joint function to produce emulated acceleration during walking
and running in humans.
AB - Understanding how humans adapt gait mechanics for a wide variety of locomotor
tasks is important for inspiring the design of robotic, prosthetic and wearable
assistive devices. We aimed to elicit the mechanical adjustments made to leg
joint functions that are required to generate accelerative walking and running,
using metrics with direct relevance to device design. Twelve healthy male
participants completed constant speed (CS) walking and running and emulated
acceleration (ACC) trials on an instrumented treadmill. External force and motion
capture data were combined in an inverse dynamics analysis. Ankle, knee and hip
joint mechanics were described and compared using angles, moments, powers and
normalized functional indexes that described each joint as relatively more:
spring, motor, damper or strut-like. To accelerate using a walking gait, the
ankle joint was switched from predominantly spring-like to motor-like, while the
hip joint was maintained as a motor, with an increase in hip motor-like function.
Accelerating while running involved no change in the primary function of any leg
joint, but involved high levels of spring and motor-like function at the hip and
ankle joints. Mechanical adjustments for ACC walking were achieved primarily via
altered limb positioning, but ACC running needed greater joint moments.
PMID- 28405378
TI - A unified model of the standard genetic code.
AB - The Rodin-Ohno (RO) and the Delarue models divide the table of the genetic code
into two classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition
from the minor or major groove sides of the tRNA acceptor stem, respectively.
These models are asymmetric but they are biologically meaningful. On the other
hand, the standard genetic code (SGC) can be derived from the primeval RNY code
(R stands for purines, Y for pyrimidines and N any of them). In this work, the RO
model is derived by means of group actions, namely, symmetries represented by
automorphisms, assuming that the SGC originated from a primeval RNY code. It
turns out that the RO-model is symmetric in a six-dimensional (6D) hypercube.
Conversely, using the same automorphisms, we show that the RO-model can lead to
the SGC. In addition, the asymmetric Delarue model becomes symmetric by means of
quotient group operations. We formulate isometric functions that convert the
class aaRS I into the class aaRS II and vice versa. We show that the four polar
requirement categories display a symmetrical arrangement in our 6D hypercube.
Altogether these results cannot be attained, neither in two nor in three
dimensions. We discuss the present unified 6D algebraic model, which is
compatible with both the SGC (based upon the primeval RNY code) and the RO-model.
PMID- 28405379
TI - Human mobility networks and persistence of rapidly mutating pathogens.
AB - Rapidly mutating pathogens may be able to persist in the population and reach an
endemic equilibrium by escaping hosts' acquired immunity. For such diseases,
multiple biological, environmental and population-level mechanisms determine the
dynamics of the outbreak, including pathogen's epidemiological traits (e.g.
transmissibility, infectious period and duration of immunity), seasonality,
interaction with other circulating strains and hosts' mixing and spatial
fragmentation. Here, we study a susceptible-infected-recovered-susceptible model
on a metapopulation where individuals are distributed in sub-populations
connected via a network of mobility flows. Through extensive numerical
simulations, we explore the phase space of pathogen's persistence and map the
dynamical regimes of the pathogen following emergence. Our results show that
spatial fragmentation and mobility play a key role in the persistence of the
disease whose maximum is reached at intermediate mobility values. We describe the
occurrence of different phenomena including local extinction and emergence of
epidemic waves, and assess the conditions for large-scale spreading. Findings are
highlighted in reference to previous studies and to real scenarios. Our work
uncovers the crucial role of hosts' mobility on the ecological dynamics of
rapidly mutating pathogens, opening the path for further studies on disease
ecology in the presence of a complex and heterogeneous environment.
PMID- 28405380
TI - Robust associations between the 20-item prosopagnosia index and the Cambridge
Face Memory Test in the general population.
AB - Developmental prosopagnosia (DP) is a neurodevelopmental condition, characterized
by lifelong face recognition deficits. Leading research groups diagnose the
condition using complementary computer-based tasks and self-report measures. In
an attempt to standardize the reporting of self-report evidence, we recently
developed the 20-item prosopagnosia index (PI20), a short questionnaire measure
of prosopagnosic traits suitable for screening adult samples for DP. Strong
correlations between scores on the PI20 and performance on the Cambridge Face
Memory Test (CFMT) appeared to confirm that individuals possess sufficient
insight into their face recognition ability to complete a self-report measure of
prosopagnosic traits. However, the extent to which people have insight into their
face recognition abilities remains contentious. A lingering concern is that
feedback from formal testing, received prior to administration of the PI20, may
have augmented the self-insight of some respondents in the original validation
study. To determine whether the significant correlation with the CFMT was an
artefact of previously delivered feedback, we sought to replicate the validation
study in individuals with no history of formal testing. We report highly
significant correlations in two independent samples drawn from the general
population, confirming: (i) that a significant relationship exists between PI20
scores and performance on the CFMT, and (ii) that this is not dependent on the
inclusion of individuals who have previously received feedback. These findings
support the view that people have sufficient insight into their face recognition
abilities to complete a self-report measure of prosopagnosic traits.
PMID- 28405381
TI - A model of urban scaling laws based on distance dependent interactions.
AB - Socio-economic related properties of a city grow faster than a linear
relationship with the population, in a log-log plot, the so-called superlinear
scaling. Conversely, the larger a city, the more efficient it is in the use of
its infrastructure, leading to a sublinear scaling on these variables. In this
work, we addressed a simple explanation for those scaling laws in cities based on
the interaction range between the citizens and on the fractal properties of the
cities. To this purpose, we introduced a measure of social potential which
captured the influence of social interaction on the economic performance and the
benefits of amenities in the case of infrastructure offered by the city. We
assumed that the population density depends on the fractal dimension and on the
distance-dependent interactions between individuals. The model suggests that when
the city interacts as a whole, and not just as a set of isolated parts, there is
improvement of the socio-economic indicators. Moreover, the bigger the
interaction range between citizens and amenities, the bigger the improvement of
the socio-economic indicators and the lower the infrastructure costs of the city.
We addressed how public policies could take advantage of these properties to
improve cities development, minimizing negative effects. Furthermore, the model
predicts that the sum of the scaling exponents of social-economic and
infrastructure variables are 2, as observed in the literature. Simulations with
an agent-based model are confronted with the theoretical approach and they are
compatible with the empirical evidences.
PMID- 28405383
TI - A new apparatus to induce lysis of planktonic microbial cells by shock
compression, cavitation and spray.
AB - Experiments were conducted on an aqueous growth medium containing cultures of
Escherichia coli (E. coli) XL1-Blue, to investigate, in a single experiment, the
effect of two types of dynamic mechanical loading on cellular integrity. A
bespoke shock tube was used to subject separate portions of a planktonic
bacterial culture to two different loading sequences: (i) shock compression
followed by cavitation, and (ii) shock compression followed by spray. The
apparatus allows the generation of an adjustable loading shock wave of magnitude
up to 300 MPa in a sterile laboratory environment. Cultures of E. coli were
tested with this apparatus and the spread-plate technique was used to measure the
survivability after mechanical loading. The loading sequence (ii) gave higher
mortality than (i), suggesting that the bacteria are more vulnerable to shear
deformation and cavitation than to hydrostatic compression. We present the
results of preliminary experiments and suggestions for further experimental work;
we discuss the potential applications of this technique to sterilize large
volumes of fluid samples.
PMID- 28405382
TI - Perceived duration of brief visual events is mediated by timing mechanisms at the
global stages of visual processing.
AB - There is a growing body of evidence pointing to the existence of modality
specific timing mechanisms for encoding sub-second durations. For example, the
duration compression effect describes how prior adaptation to a dynamic visual
stimulus results in participants underestimating the duration of a sub-second
test stimulus when it is presented at the adapted location. There is substantial
evidence for the existence of both cortical and pre-cortical visual timing
mechanisms; however, little is known about where in the processing hierarchy the
cortical mechanisms are likely to be located. We carried out a series of
experiments to determine whether or not timing mechanisms are to be found at the
global processing level. We had participants adapt to random dot patterns that
varied in their motion coherence, thus allowing us to probe the visual system at
the level of motion integration. Our first experiment revealed a positive linear
relationship between the motion coherence level of the adaptor stimulus and
duration compression magnitude. However, increasing the motion coherence level in
a stimulus also results in an increase in global speed. To test whether duration
compression effects were driven by global speed or global motion, we repeated the
experiment, but kept global speed fixed while varying motion coherence levels.
The duration compression persisted, but the linear relationship with motion
coherence was absent, suggesting that the effect was driven by adapting global
speed mechanisms. Our results support previous claims that visual timing
mechanisms persist at the level of global processing.
PMID- 28405384
TI - A new low-turbulence wind tunnel for animal and small vehicle flight experiments.
AB - Our understanding of animal flight benefits greatly from specialized wind tunnels
designed for flying animals. Existing facilities can simulate laminar flow during
straight, ascending and descending flight, as well as at different altitudes.
However, the atmosphere in which animals fly is even more complex. Flow can be
laminar and quiet at high altitudes but highly turbulent near the ground, and
gusts can rapidly change wind speed. To study flight in both laminar and
turbulent environments, a multi-purpose wind tunnel for studying animal and small
vehicle flight was built at Stanford University. The tunnel is closed-circuit and
can produce airspeeds up to 50 m s-1 in a rectangular test section that is 1.0 m
wide, 0.82 m tall and 1.73 m long. Seamless honeycomb and screens in the airline
together with a carefully designed contraction reduce centreline turbulence
intensities to less than or equal to 0.030% at all operating speeds. A large
diameter fan and specialized acoustic treatment allow the tunnel to operate at
low noise levels of 76.4 dB at 20 m s-1. To simulate high turbulence, an active
turbulence grid can increase turbulence intensities up to 45%. Finally, an open
jet configuration enables stereo high-speed fluoroscopy for studying
musculoskeletal control in turbulent flow.
PMID- 28405385
TI - Cranial arterial patterns of the alpaca (Camelidae: Vicugna pacos).
AB - Artiodactyl cranial arterial patterns deviate significantly from the standard
mammalian pattern, most notably in the possession of a structure called the
carotid rete (CR)-a subdural arterial meshwork that is housed within the
cavernous venous sinus, replacing the internal carotid artery (ICA). This
relationship between the CR and the cavernous sinus facilitates a suite of unique
physiologies, including selective brain cooling. The CR has been studied in a
number of artiodactyls; however, to my knowledge, only a single study to date
documents a subset of the cranial arteries of New World camelids (llamas,
alpacas, vicugnas and guanacoes). This study is the first complete description of
the cranial arteries of a New World camelid species, the alpaca (Vicugna pacos),
and the first description of near-parturition cranial arterial morphology within
New World camelids. This study finds that the carotid arterial system is
conserved between developmental stages in the alpaca, and differs significantly
from the pattern emphasized in other long-necked ruminant artiodactyls in that a
patent, homologous ICA persists through the animal's life.
PMID- 28405386
TI - The importance of temperature fluctuations in understanding mosquito population
dynamics and malaria risk.
AB - Temperature is a key environmental driver of Anopheles mosquito population
dynamics; understanding its central role is important for these malaria vectors.
Mosquito population responses to temperature fluctuations, though important
across the life history, are poorly understood at a population level. We used
stage-structured, temperature-dependent delay-differential equations to conduct a
detailed exploration of the impacts of diurnal and annual temperature
fluctuations on mosquito population dynamics. The model allows exploration of
temperature-driven temporal changes in adult age structure, giving insights into
the population's capacity to vector malaria parasites. Because of temperature
dependent shifts in age structure, the abundance of potentially infectious
mosquitoes varies temporally, and does not necessarily mirror the dynamics of the
total adult population. In addition to conducting the first comprehensive
theoretical exploration of fluctuating temperatures on mosquito population
dynamics, we analysed observed temperatures at four locations in Africa covering
a range of environmental conditions. We found both temperature and precipitation
are needed to explain the observed malaria season in these locations, enhancing
our understanding of the drivers of malaria seasonality and how temporal disease
risk may shift in response to temperature changes. This approach, tracking both
mosquito abundance and age structure, may be a powerful tool for understanding
current and future malaria risk.
PMID- 28405387
TI - Accuracy of climate-based forecasts of pathogen spread.
AB - Species distribution models (SDMs) are a tool for predicting the eventual
geographical range of an emerging pathogen. Most SDMs, however, rely on an
assumption of equilibrium with the environment, which an emerging pathogen, by
definition, has not reached. To determine if some SDM approaches work better than
others for modelling the spread of emerging, non-equilibrium pathogens, we
studied time-sensitive predictive performance of SDMs for Batrachochytrium
dendrobatidis, a devastating infectious fungus of amphibians, using multiple
methods trained on time-incremented subsets of the available data. We split our
data into timeline-based training and testing sets, and evaluated models on each
set using standard performance criteria, including AUC, kappa, false negative
rate and the Boyce index. Of eight models examined, we found that boosted
regression trees and random forests performed best, closely followed by MaxEnt.
As expected, predictive performance generally improved with the length of time
series used for model training. These results provide information on how quickly
the potential extent of an emerging disease may be determined, and identify which
modelling frameworks are likely to provide useful information during the early
phases of pathogen expansion.
PMID- 28405388
TI - Diet dichotomy between two migrant seabirds breeding near a high Arctic polynya.
AB - High Arctic polynyas are predictable areas of open water, which offer long
distance migrant seabirds a reliable source of food during a period when they
have to replenish and accumulate energy for reproduction. Investigating the
interaction between species nesting sympatrically in the vicinity of polynyas
should provide insights into the role that such oceanographic features play for
pre-breeding seabirds. We used stable isotopes (delta13C and delta15N) to compare
the diet of two ground-nesting seabirds, Sabine's gull (Xema sabini) and Arctic
tern (Sterna paradisaea), nesting on an island adjacent to a recurring polynya in
the Canadian high Arctic in 2008 and 2009. We show that, unlike Arctic terns, the
diet of Sabine's gulls appears to include a non-negligible amount of
terrestrially derived prey during early incubation, and that overall both species
segregate their dietary niche during pre-laying and early incubation.
PMID- 28405389
TI - Mixing of porpoise ecotypes in southwestern UK waters revealed by genetic
profiling.
AB - Contact zones between ecotypes are windows for understanding how species may
react to climate changes. Here, we analysed the fine-scale genetic and
morphological variation in harbour porpoises (Phocoena phocoena) around the UK by
genotyping 591 stranded animals at nine microsatellite loci. The data were
integrated with a prior study to map at high resolution the contact zone between
two previously identified ecotypes meeting in the northern Bay of Biscay.
Clustering and spatial analyses revealed that UK porpoises are derived from two
genetic pools with porpoises from the southwestern UK being genetically
differentiated, and having larger body sizes compared to those of other UK areas.
Southwestern UK porpoises showed admixed ancestry between southern and northern
ecotypes with a contact zone extending from the northern Bay of Biscay to the
Celtic Sea and Channel. Around the UK, ancestry blends from one genetic group to
the other along a southwest--northeast axis, correlating with body size
variation, consistent with previously reported morphological differences between
the two ecotypes. We also detected isolation by distance among juveniles but not
in adults, suggesting that stranded juveniles display reduced intergenerational
dispersal. The fine-scale structure of this admixture zone raises the question of
how it will respond to future climate change and provides a reference point for
further study.
PMID- 28405390
TI - The wing pattern of Moerarchis Durrant, 1914 (Lepidoptera: Tineidae) clarifies
transitions between predictive models.
AB - The evolution of wing pattern in Lepidoptera is a popular area of inquiry but few
studies have examined microlepidoptera, with fewer still focusing on
intraspecific variation. The tineid genus Moerarchis Durrant, 1914 includes two
species with high intraspecific variation of wing pattern. A subset of the
specimens examined here provide, to my knowledge, the first examples of wing
patterns that follow both the 'alternating wing-margin' and 'uniform wing-margin'
models in different regions along the costa. These models can also be evaluated
along the dorsum of Moerarchis, where a similar transition between the two models
can be seen. Fusion of veins is shown not to effect wing pattern, in agreement
with previous inferences that the plesiomorphic location of wing veins constrains
the development of colour pattern. The significant correlation between wing
length and number of wing pattern elements in Moerarchis australasiella shows
that wing size can act as a major determinant of wing pattern complexity. Lastly,
some M. australasiella specimens have wing patterns that conform entirely to the
'uniform wing-margin' model and contain more than six bands, providing new
empirical insight into the century-old question of how wing venation constrains
wing patterns with seven or more bands.
PMID- 28405391
TI - Red fluorescence of the triplefin Tripterygion delaisi is increasingly visible
against background light with increasing depth.
AB - The light environment in water bodies changes with depth due to the absorption of
short and long wavelengths. Below 10 m depth, red wavelengths are almost
completely absent rendering any red-reflecting animal dark and achromatic.
However, fluorescence may produce red coloration even when red light is not
available for reflection. A large number of marine taxa including over 270 fish
species are known to produce red fluorescence, yet it is unclear under which
natural light environment fluorescence contributes perceptively to their colours.
To address this question we: (i) characterized the visual system of Tripterygion
delaisi, which possesses fluorescent irides, (ii) separated the colour of the
irides into its reflectance and fluorescence components and (iii) combined these
data with field measurements of the ambient light environment to calculate depth
dependent perceptual chromatic and achromatic contrasts using visual modelling.
We found that triplefins have cones with at least three different spectral
sensitivities, including differences between the two members of the double cones,
giving them the potential for trichromatic colour vision. We also show that
fluorescence contributes increasingly to the radiance of the irides with
increasing depth. Our results support the potential functionality of red
fluorescence, including communicative roles such as species and sex identity, and
non-communicative roles such as camouflage.
PMID- 28405392
TI - Enhanced hydrogen evolution reaction on hybrids of cobalt phosphide and
molybdenum phosphide.
AB - Production of hydrogen from water electrolysis has stimulated the search of
sustainable electrocatalysts as possible alternatives. Recently, cobalt phosphide
(CoP) and molybdenum phosphide (MoP) received great attention owing to their
superior catalytic activity and stability towards the hydrogen evolution reaction
(HER) which rivals platinum catalysts. In this study, we synthesize and study a
series of catalysts based on hybrids of CoP and MoP with different Co/Mo ratio.
The HER activity shows a volcano shape and reaches a maximum for Co/Mo = 1. Tafel
analysis indicates a change in the dominating step of Volmer-Hyrovsky mechanism.
Interestingly, X-ray diffraction patterns confirmed a major ternary interstitial
hexagonal CoMoP2 crystal phase is formed which enhances the electrochemical
activity.
PMID- 28405393
TI - Lung anatomy and histology of the extant coelacanth shed light on the loss of air
breathing during deep-water adaptation in actinistians.
AB - Lungs are specialized organs originated from the posterior pharyngeal cavity and
considered as plesiomorphic for osteichthyans, as they are found in extant basal
actinopterygians (i.e. Polypterus) and in all major groups of extant
sarcopterygians. The presence of a vestigial lung in adult stages of the extant
coelacanth Latimeria chalumnae is the result of allometric growth during
ontogeny, in relation with long-time adaptation to deep water. Here, we present
the first detailed histological and anatomical description of the lung of
Latimeria chalumnae, providing new insights into its arrested differentiation in
an air-breathing complex, mainly represented by the absence of pneumocytes and of
compartmentalization in the latest ontogenetic stages.
PMID- 28405394
TI - Brain size in birds is related to traffic accidents.
AB - Estimates suggest that perhaps a quarter of a billion birds are killed by traffic
annually across the world. This is surprising because birds have been shown to
learn speed limits. Birds have also been shown to adapt to the direction of
traffic and lane use, and this apparently results in reduced risks of fatal
traffic accidents. Such behavioural differences suggest that individual birds
that are not killed in traffic should have larger brains for their body size. We
analysed the link between being killed by traffic and relative brain mass in 3521
birds belonging to 251 species brought to a taxidermist. Birds that were killed
in traffic indeed had relatively smaller brains, while there was no similar
difference for liver mass, heart mass or lung mass. These findings suggest that
birds learn the behaviour of car drivers, and that they use their brains to
adjust behaviour in an attempt to avoid mortality caused by rapidly and
predictably moving objects.
PMID- 28405395
TI - Pulse of inflammatory proteins in the pregnant uterus of European polecats
(Mustela putorius) leading to the time of implantation.
AB - Uterine secretory proteins protect the uterus and conceptuses against infection,
facilitate implantation, control cellular damage resulting from implantation, and
supply pre-implantation embryos with nutrients. Unlike in humans, the early
conceptus of the European polecat (Mustela putorius; ferret) grows and develops
free in the uterus until implanting at about 12 days after mating. We found that
the proteins appearing in polecat uteri changed dramatically with time leading to
implantation. Several of these proteins have also been found in pregnant uteri of
other eutherian mammals. However, we found a combination of two increasingly
abundant proteins that have not been recorded before in pre-placentation uteri.
First, the broad-spectrum proteinase inhibitor alpha2-macroglobulin rose to
dominate the protein profile by the time of implantation. Its functions may be to
limit damage caused by the release of proteinases during implantation or
infection, and to control other processes around sites of implantation. Second,
lipocalin-1 (also known as tear lipocalin) also increased substantially in
concentration. This protein has not previously been recorded as a uterine
secretion in pregnancy in any species. If polecat lipocalin-1 has similar
biological properties to that of humans, then it may have a combined function in
antimicrobial protection and transporting or scavenging lipids. The changes in
the uterine secretory protein repertoire of European polecats is therefore
unusual, and may be representative of pre-placentation supportive uterine
secretions in mustelids (otters, weasels, badgers, mink, wolverines) in general.
PMID- 28405396
TI - Multimodal communication in courting fiddler crabs reveals male performance
capacities.
AB - Courting males often perform different behavioural displays that demonstrate
aspects of their quality. Male fiddler crabs, Uca sp., are well known for their
repetitive claw-waving display during courtship. However, in some species, males
produce an additional signal by rapidly stridulating their claw, creating a
'drumming' vibrational signal through the substrate as a female approaches, and
even continue to drum once inside their burrow. Here, we show that the switch
from waving to drumming might provide additional information to the female about
the quality of a male, and the properties of his burrow (multiple message
hypothesis). Across males there was, however, a strong positive relationship
between aspects of their waving and drumming displays, suggesting that drumming
adheres to some predictions of the redundant signal hypothesis for multimodal
signalling. In field experiments, we show that recent courtship is associated
with a significant reduction in male sprint speed, which is commensurate with an
oxygen debt. Even so, males that wave and drum more vigorously than their
counterparts have a higher sprint speed. Drumming appears to be an energetically
costly multimodal display of quality that females should attend to when making
their mate choice decisions.
PMID- 28405397
TI - Dynamics of cilia length in left-right development.
AB - Reduction in the length of motile cilia in the zebrafish left-right organizer
(LRO), also known as Kupffer's vesicle, has a large impact on left-right
development. Here we demonstrate through genetic overexpression in zebrafish
embryos and mathematical modelling that the impact of increased motile cilia
length in embryonic LRO fluid flow is milder than that of short cilia. Through
Arl13b overexpression, which increases cilia length without impacting cilia beat
frequency, we show that the increase in cilium length is associated with a
decrease in beat amplitude, resulting in similar flow strengths for Arl13b
overexpression and wild-type (WT) embryos, which were not predicted by current
theory. Longer cilia exhibit pronounced helical beat patterns and, consequently,
lower beat amplitudes relative to WT, a result of an elastohydrodynamic shape
transition. For long helical cilia, fluid dynamics modelling predicts a mild
(approx. 12%) reduction in the torque exerted on the fluid relative to the WT,
resulting in a proportional reduction in flow generation. This mild reduction is
corroborated by experiments, providing a mechanism for the mild impact on organ
situs.
PMID- 28405398
TI - Mechanisms of vortices termination in the cardiac muscle.
AB - We propose a solution to a long-standing problem: how to terminate multiple
vortices in the heart, when the locations of their cores and their critical time
windows are unknown. We scan the phases of all pinned vortices in parallel with
electric field pulses (E-pulses). We specify a condition on pacing parameters
that guarantees termination of one vortex. For more than one vortex with
significantly different frequencies, the success of scanning depends on chance,
and all vortices are terminated with a success rate of less than one. We found
that a similar mechanism terminates also a free (not pinned) vortex. A series of
about 500 experiments with termination of ventricular fibrillation by E-pulses in
pig isolated hearts is evidence that pinned vortices, hidden from direct
observation, are significant in fibrillation. These results form a physical basis
needed for the creation of new effective low energy defibrillation methods based
on the termination of vortices underlying fibrillation.
PMID- 28405399
TI - Strain identification and quorum sensing inhibition characterization of marine
derived Rhizobium sp. NAO1.
AB - A novel strategy for combating pathogens is through the ongoing development and
use of anti-quorum sensing (QS) treatments such as therapeutic bacteria or their
anti-QS substances. Relatively little is known about the bacteria that inhabit
the open ocean and of their potential anti-pathogenic attributes; thus, in an
initiative to identify these types of therapeutic bacteria, planktonic microbes
from the North Atlantic Ocean were collected, isolated, cultured and screened for
anti-QS activity. Screening analysis identified one such strain, Rhizobium sp.
NAO1. Extracts of Rhizobium sp. NAO1 were identified via ultra-performance liquid
chromatography (UPLC) analysis. They were shown to contain N-acyl homoserine
lactone (AHL)-based QS analogues (in particular, the N-butyryl homoserine lactone
(C4-AHL) analogue) and could disrupt biofilm formation by Pseudomonas aeruginosa
PAO1. QS inhibition was confirmed using confocal scanning laser microscopy and
growth curves, and it was shown to occur in a dose-dependent manner without
affecting bacterial growth. Secondary metabolites of Rhizobium sp. NAO1 inhibited
PAO1 pathogenicity by downregulating AHL-mediated virulence factors such as
elastase activity and siderophore production. Furthermore, as a result of biofilm
structure damage, the secondary metabolite products of Rhizobium sp. NAO1
significantly increased the sensitivity of PAO1 to aminoglycoside antibiotics.
Our results demonstrated that Rhizobium sp. strain NAO1 has the ability to
disrupt P. aeruginosa PAO1 biofilm architecture, in addition to attenuating P.
aeruginosa PAO1 virulence factor production and pathogenicity. Therefore, the
newly identified ocean-derived Rhizobium sp. NAO1 has the potential to serve as a
QS inhibitor and may be a new microbial resource for drug development.
PMID- 28405400
TI - Microbe biogeography tracks water masses in a dynamic oceanic frontal system.
AB - Dispersal limitation, not just environmental selection, plays an important role
in microbial biogeography. The distance-decay relationship is thought to be weak
in habitats where dispersal is high, such as in the pelagic environment, where
ocean currents facilitate microbial dispersal. Most studies of microbial
community composition to date have observed little geographical heterogeneity on
a regional scale (100 km). We present a study of microbial communities across a
dynamic frontal zone in the southwest Indian Ocean and investigate the spatial
structure of the microbes with respect to the different water masses separated by
these fronts. We collected 153 samples of free-living microorganisms from five
seamounts located along a gradient from subtropical to subantarctic waters and
across three depth layers: (i) the sub-surface chlorophyll maximum (approx. 40
m), (ii) the bottom of the euphotic zone (approx. 200 m), and (iii) the benthic
boundary layer (300-2000 m). Diversity and abundance of microbial operational
taxonomic units (OTUs) were assessed by amplification and sequencing of the 16S
rRNA gene on an Illumina MiSeq platform. Multivariate analyses showed that
microbial communities were structured more strongly by depth than by latitude,
with similar phyla occurring within each depth stratum across seamounts. The deep
layer was homogeneous across the entire survey area, corresponding to the spread
of Antarctic intermediate water. However, within both the sub-surface layer and
the intermediate depth stratum there was evidence for OTU turnover across fronts.
The microbiome of these layers appears to be divided into three distinct
biological regimes corresponding to the subantarctic surface water, the
convergence zone and subtropical. We show that microbial biogeography across
depth and latitudinal gradients is linked to the water masses the microbes
persist in, resulting in regional patterns of microbial biogeography that
correspond to the regional scale physical oceanography.
PMID- 28405401
TI - Drosophila enhancer-Gal4 lines show ectopic expression during development.
AB - In Drosophila melanogaster the most widely used technique to drive gene
expression is the binary UAS/Gal4 system. We show here that a set of nervous
system specific enhancers (elav, D42/Toll-6, OK6/RapGAP1) display ectopic
activity in epithelial tissues during development, which is seldom considered in
experimental studies. This ectopic activity is variable, unstable and influenced
by the primary sequence of the enhancer and the insertion site in the chromosome.
In addition, the ectopic activity is independent of the protein expressed, Gal4,
as it is reproduced also with the expression of Gal80. Another enhancer, LN2 from
the sex lethal (Sxl) gene, shows sex-dependent features in its ectopic
expression. Feminization of LN2 expressing males does not alter the male specific
pattern indicating that the sexual dimorphism of LN2 expression is an intrinsic
feature of this enhancer. Other X chromosome enhancers corresponding to genes not
related to sex determination do not show sexual dimorphism in their ectopic
expressions. Although variable and unstable, the ectopic activation of enhancer
Gal4 lines seems to be regulated in terms of tissue and intensity. To
characterize the full domain of expression of enhancer-Gal4 constructs is
relevant for the design of transgenic animal models and biotechnology tools, as
well as for the correct interpretation of developmental and behavioural studies
in which Gal4 lines are used.
PMID- 28405402
TI - Absence of population structure across elevational gradients despite large
phenotypic variation in mountain chickadees (Poecile gambeli).
AB - Montane habitats are characterized by predictably rapid heterogeneity along
elevational gradients and are useful for investigating the consequences of
environmental heterogeneity for local adaptation and population genetic
structure. Food-caching mountain chickadees inhabit a continuous elevation
gradient in the Sierra Nevada, and birds living at harsher, high elevations have
better spatial memory ability and exhibit differences in male song structure and
female mate preference compared to birds inhabiting milder, low elevations. While
high elevation birds breed, on average, two weeks later than low elevation birds,
the extent of gene flow between elevations is unknown. Despite phenotypic
variation and indirect evidence for local adaptation, population genetic analyses
based on 18 073 single nucleotide polymorphisms across three transects of high
and low elevation populations provided no evidence for genetic differentiation.
Analyses based on individual genotypes revealed no patterns of clustering,
pairwise estimates of genetic differentiation (FST, Nei's D) were very low, and
AMOVA revealed no evidence for genetic variation structured by transect or by low
and high elevation sites within transects. In addition, we found no consistent
evidence for strong parallel allele frequency divergence between low and high
elevation sites within the three transects. Large elevation-related phenotypic
variation may be maintained by strong selection despite gene flow and future work
should focus on the mechanisms underlying such variation.
PMID- 28405403
TI - Niche partitioning and the role of intraspecific niche variation in structuring a
guild of generalist anurans.
AB - Intra-population niche differences in generalist foragers have captured the
interest of ecologists, because such individuality can have important ecological
and evolutionary implications. Few researchers have investigated how these
differences affect the relationships among ecologically similar, sympatric
species. Using stable isotopes, stomach contents, morphology and habitat
preference, we examined niche partitioning within a group of five anurans and
determined whether variation within species could facilitate resource
partitioning. Species partitioned their niches by trophic level and by foraging
habitat. However, there was considerable intraspecific variation in trophic
level, with larger individuals generally feeding at higher trophic levels. For
species at intermediate trophic levels, smaller individuals overlapped in trophic
level with individuals of smaller species and larger individuals overlapped with
the smallest individuals from larger species. Species varied in carbon isotopes;
species with enriched carbon isotope ratios foraged farther from ponds, whereas
species with depleted carbon isotope values foraged closer to ponds. Our study
shows that these species partition their niches by feeding at different trophic
levels and foraging at different distances from ponds. The intraspecific
variation in trophic level decreased the number of individuals from each species
that overlapped in trophic level with individuals from other species, which can
facilitate species coexistence.
PMID- 28405404
TI - The elastic theory of shells using geometric algebra.
AB - We present a novel derivation of the elastic theory of shells. We use the
language of geometric algebra, which allows us to express the fundamental laws in
component-free form, thus aiding physical interpretation. It also provides the
tools to express equations in an arbitrary coordinate system, which enhances
their usefulness. The role of moments and angular velocity, and the apparent use
by previous authors of an unphysical angular velocity, has been clarified through
the use of a bivector representation. In the linearized theory, clarification of
previous coordinate conventions which have been the cause of confusion is
provided, and the introduction of prior strain into the linearized theory of
shells is made possible.
PMID- 28405405
TI - Correction to 'A Bayesian bird's eye view of 'Replications of important results
in social psychology'.
AB - [This corrects the article DOI: 10.1098/rsos.160426.].
PMID- 28405406
TI - Heterogeneous resource allocation can change social hierarchy in public goods
games.
AB - Public goods games (PGGs) represent one of the most useful tools to study group
interactions. However, even if they could provide an explanation for the
emergence and stability of cooperation in modern societies, they are not able to
reproduce some key features observed in social and economical interactions. The
typical shape of wealth distribution-known as Pareto Law-and the microscopic
organization of wealth production are two of them. Here, we introduce a
modification to the classical formulation of PGGs that allows for the emergence
of both of these features from first principles. Unlike traditional PGGs, where
players contribute equally to all the games in which they participate, we allow
individuals to redistribute their contribution according to what they earned in
previous rounds. Results from numerical simulations show that not only a Pareto
distribution for the pay-offs naturally emerges but also that if players do not
invest enough in one round they can act as defectors even if they are formally
cooperators. Our results not only give an explanation for wealth heterogeneity
observed in real data but also point to a conceptual change on cooperation in
collective dilemmas.
PMID- 28405407
TI - Invasive Drosophila suzukii facilitates Drosophila melanogaster infestation and
sour rot outbreaks in the vineyards.
AB - How do invasive pests affect interactions between members of pre-existing
agrosystems? The invasive pest Drosophila suzukii is suspected to be involved in
the aetiology of sour rot, a grapevine disease that otherwise develops following
Drosophila melanogaster infestation of wounded berries. We combined field
observations with laboratory assays to disentangle the relative roles of both
Drosophila in disease development. We observed the emergence of numerous D.
suzukii, but no D. melanogaster flies, from bunches that started showing mild
sour rot symptoms days after field collection. However, bunches that already
showed severe rot symptoms in the field mostly contained D. melanogaster. In the
laboratory, oviposition by D. suzukii triggered sour rot development. An
independent assay showed the disease increased grape attractiveness to
ovipositing D. melanogaster females. Our results suggest that in invaded
vineyards, D. suzukii facilitates D. melanogaster infestation and, consequently,
favours sour rot outbreaks. Rather than competing with close species, the invader
subsequently permits their reproduction in otherwise non-accessible resources and
may cause more frequent, or more extensive, disease outbreaks.
PMID- 28405408
TI - Improving our understanding of the in vivo modelling of psychotic disorders: A
protocol for a systematic review and meta-analysis.
AB - Psychosis represents a set of symptoms against which current available treatments
are not universally effective and are often accompanied by adverse side effects.
Clinical management could potentially be improved with a greater understanding of
the underlying biology and subsequently with the introduction of novel
treatments. Since many clinical drug candidates are identified through in vivo
modelling, a deeper understanding of the pre-clinical field, might help us
understand why translation of results from animal models to inform mental health
clinical practice has so far been weak. We set out to give a shallow, but broad
unbiased overview of experiments looking at the in vivo modelling of psychotic
disorders using a systematic review and meta-analysis. This protocol describes
the exact methodology we propose to follow in order to quantitatively review both
studies characterizing a model and those experiments that investigate the effects
of novel therapeutic options. We are interested in assessing the prevalence of
the reporting of measures to reduce risk of bias, and the internal and external
validity of the animal models and outcome measures used to validate these models.
This generation of strong empirical evidence has the potential to identify areas
for improvement, make suggestions for future research avenues, and ultimately
inform what we think we know to improve the current attrition rate between bench
and bedside in psychosis research. A review like this will also support the
reduction of animal numbers used in research and the refinement of experiments to
maximize their value in informing the field.
PMID- 28405409
TI - Effects of communication skill training (CST) based on SPIKES for insurance
covered pharmacy pharmacists to interact with simulated cancer patients.
AB - BACKGROUND: With the development of pharmacotherapy and radiotherapy, cancer
treatment is being shifted from surgical to outpatient services, consequently
increasing insurance-covered pharmacies' frequency of dealing with cancer
patients. As the psychology of these patients is complex, it is necessary for
pharmacists to educate them in consideration of their cognitive/medical and
psychosocial aspects. This study analyzed cancer patient management by
pharmacists working in such pharmacies and their communication skills before and
after communication skill training based on SPIKES, a six-step protocol for
delivering bad news, to confirm the usefulness of such training. METHODS: The
study involved 20 pharmacists working in insurance-covered pharmacies within
Aichi Prefecture. Before and after communication skill training, role-play
sessions were held using standardized patients, whose levels of satisfaction were
subsequently measured. Patient management by the pharmacists was analyzed using
the Roter Interaction Analysis System as a method to analyze dialogues. RESULTS:
The rate of each category, representing the pharmacists' conversation styles when
dealing with the patients, changed after communication skill training as follows:
[Giving information]: decreased from 37.0 to 27.6%; [Empathy statements]:
increased from 12.0 to 17.2%; and [Data gathering]: increased from 18.0 to 23.3%.
The increase was particularly marked in: [Acceptance], accepting patients'
emotions and events in line with [Empathy statements]; [Promoting dialogues] as a
sub-category of [Building a relationship]; and [Checks for understanding] as a
sub-category of [Data gathering]. Furthermore, the results of pharmacist
assessment by the patients, including their levels of overall satisfaction,
showed significant correlations with [Empathy statements] and [Building a
relationship]. CONCLUSIONS: Communication skill training may be effective to
improve pharmacists' conversation styles to listen to patients more attentively,
accept their emotions, and provide education in accordance with their needs,
rather than unilaterally providing information. TRIAL REGISTRATION: The study was
approved by the Ethical Review Board of Meijo University as a research activity
involving humans (approval number: H26-1).
PMID- 28405410
TI - Porcine health management - the pig in a central position.
AB - We are proud to launch a new open access journal, entitled Porcine Health
Management (PHM). This new journal, which puts the pig in a central position, has
been jointly established by the European College of Porcine Health and Management
and the European Association of Porcine Health Management. PHM is interested in
publishing articles of high quality and novelty, but we also consider research
results of more general interest and clinical features to the readers. We believe
that putting the pig at the center of this journal is unique and will serve both
our favored animal species and our professions. We hope that you will enjoy the
PHM journal and that you will consider it when deciding where to publish your
work.
PMID- 28405411
TI - Save the pig tail.
AB - Tail biting is a common problem in modern pig production and has a negative
impact on both animal welfare and economic result of the farm. Tail biting risk
is increased by management and housing practices that fail to meet the basic
needs of pigs. Tail docking is commonly used to reduce the risk of tail biting,
but tail docking in itself is a welfare problem, as it causes pain to the pigs,
and facilitates suboptimal production methods from a welfare point-of-view. When
evaluating the cost and benefit of tail docking, it is important to consider
negative impacts of both tail docking and tail biting. It is also essential to
realize that even though 100% of the pigs are normally docked, only a minority
will end up bitten, even in the worst case. In addition, data suggests that tail
biting can be managed to an acceptable level even without tail docking, by
correcting the production system to better meet the basic needs of the pigs.
PMID- 28405412
TI - Serum haptoglobin dynamics in pigs vaccinated or not vaccinated against porcine
circovirus type 2.
AB - The present work describes the serum haptoglobin (Hp) dynamics in piglets
vaccinated and non-vaccinated with a commercial porcine circovirus type 2 (PCV2)
vaccine at 3 weeks of age, and its relationship with the average daily weight
gain (ADWG). The field study was carried out on two farms (A and B) with a
previous clinical history of PCV2-systemic disease (PCV2-SD). The aim of the
study was to assess whether Hp could be used as a surrogate marker of PCV2
vaccine efficacy. PCV2 infection was confirmed by quantitative real time PCR
(qPCR) in pigs from both farms, but PCV2-SD was only diagnosed in farm A. No
statistically significant relation was found between serum Hp concentration and
the percentage of qPCR positive animals and the treatment applied (PCV2
vaccination) in both farms. On the other hand, using linear regression analysis,
a significant negative correlation between the area under the curve of Hp (AUCHp)
and ADWG was observed for farm A (p < 0.00001) and B (p = 0.01). Based on the
obtained determination coefficient (R2) values, AUCHp explained 20.0 and 11.6% of
the observed ADWG for farms A and B, respectively. The present study supports
that the measurement of acute phase proteins may be an indicator of ADWG in pig
farms, but it was not apparently feasible to use the serum Hp concentration as a
surrogate marker of PCV2 vaccine efficacy.
PMID- 28405413
TI - A comparison between lesions found during meat inspection of finishing pigs
raised under organic/free-range conditions and conventional, indoor conditions.
AB - It is often argued that pigs raised under less intensive production conditions -
such as organic or free-range - have a higher level of animal welfare compared
with conventionally raised pigs. To look into this, an analysis of data from a
large Danish abattoir slaughtering organic, free-range, and conventionally raised
finishing pigs was undertaken. First, the requirements for each of the three
types of production systems were investigated. Next, meat inspection data from a
period of 1 year were collected. These covered 201,160 organic/free-range pigs
and 1,173,213 conventionally raised pigs. The prevalence of each individual type
of lesion was calculated, followed by a statistical comparison between the
prevalences in organic/free-range and conventional pigs. Because of the large
number of data, the P-value for significance was lowered to P = 0.001, and only
biological associations reflecting Odds Ratios above 1.2 or below 0.8 were
considered to be of significance. The majority of the lesion types were recorded
infrequently (<4%). Only chronic pleuritis was a common finding. A total of 13
lesion types were more frequent among organic/free-range pigs than among
conventional pigs - among others old fractures, tail lesions and osteomyelitis.
Four lesion types were equally frequent in the two groups: chronic pneumonia,
chronic pleuritis, fresh fracture, and abscess in head/ear. Four lesion types
were recorded less frequently among organic/free-range pigs compared with
conventionally raised pigs. These included abscess in leg/toe, hernia and
scar/hock lesion. Possible associations between the individual lesion types and
the production systems - including the requirements for each system - are
discussed. The results emphasize the importance of using direct animal based
parameters when evaluating animal welfare in different types of production
systems. Moreover, individual solutions to the health problems observed in a herd
should be found, e.g. in collaboration with the veterinary practitioner and other
advisors.
PMID- 28405414
TI - A two-year follow-up study of the PCV2 status of a Danish pig herd that was
initially assumed to be PCV2-free.
AB - BACKGROUND: A longitudinal study was carried out to investigate whether a herd
that had previously tested negative for porcine circovirus type 2 (PCV2) by
polymerase chain reaction (PCR) was free of PCV2 or whether the negative profiles
indicate that the level of PCV2 varies over time. RESULTS: In eight Danish herds
that had initially tested negative for PCV2 by quantitative polymerase chain
reaction (PCR), additional sampling was performed. Only one of the herds was
still PCV2-negative in the additional sampling and was included in the study. The
herd was a finishing herd, subclinically infected with PCV2, but vaccinated
against PCV2 to improve performance. The herd was monitored by taking blood
samples every seventh week over a period of two years and was not found to be
continuously negative for PCV2 by PCR. The first time PCV2 was detected by PCR,
in May 2010, PCV2 vaccination had been withdrawn from the herd, and at the same
time the herd was infected with porcine reproductive and respiratory syndrome
virus (PRRS). The PCV2-negative status, measured by PCR, was obtained in the
first sampling after the PCV2 vaccination had been reintroduced. When PCV2
vaccination was withdrawn again in September 2011, the herd tested positive for
PCV2 by PCR, and this time it continued to be PCV2-positive, even though PCV2
vaccination had been reintroduced. CONCLUSION: A Danish finishing herd that
appeared to be PCV2-free from the start of a period of two years was not free of
PCV2 during the entire period.
PMID- 28405415
TI - Implementation of a vaccine against Shigatoxin 2e in a piglet producing farm with
problems of Oedema disease: case study.
AB - Oedema disease is one of the major diseases in pigs during the nursery period. It
is caused by Shigatoxin 2e producing strains of Escherichia coli. In order to
combat the disease, the metaphylactic use of colistin sulphate and zinc oxide is
widely spread. Additionally, special feeding regimens such as the reduction of
the amount of crude protein and the increase of the amount of crude fibre are
applied. The goal of this study was to test the efficacy of a vaccine against
Oedema disease caused by Shigatoxin 2e in a field trial on a farm with a history
of Oedema disease in nursery pigs. The study was carried out on a Dutch farm with
600 sows and a one-week farrowing rhythm and lasted for the time of one year.
During this time all piglets were vaccinated with 1 ml ECOPORC SHIGA at the
average age of 4 days. The parameters Overall mortality, use of antimicrobials in
general, calculated as defined daily dose per animal, use of colistin sulphate
and the weight gain were evaluated for all nursery pigs and compared to
historical data of animals from the same period of time directly prior to the
study serving as a historical control group. The previous mortality in the
nursery of 7.7% was significantly reduced to 1.3% after vaccination. The
metaphylactic use of colistin sulphate during the nursery period was stopped
during the study because no deaths due to Oedema disease had occurred anymore
after beginning of vaccination. The defined daily dose per animal per month was
significantly reduced from a mean of 1.050 in the year 2012 to a mean of 0.215 in
the year 2013. The defined daily dose per animal per year was therefore
relevantly reduced from 12.6 in 2012 to 2.6 in 2013. These results show that on
this farm Oedema disease can not only be controlled successfully by vaccination
but also that vaccination can significantly reduce the use of antimicrobials in
the nursery period.
PMID- 28405416
TI - An evaluation of porcine epidemic diarrhea virus survival in individual feed
ingredients in the presence or absence of a liquid antimicrobial.
AB - BACKGROUND: Contaminated complete feed and porcine plasma are risk factors for
PEDV introduction to farms and a liquid antimicrobial has been proven useful for
reducing risk. This study provides information on the survivability of PEDV
across common swine feed ingredients in the presence or absence of the liquid
antimicrobial. RESULTS: Eighteen ingredients commonly included in commercial
swine diets were selected, including 3 grain sources (corn, soybean meal (SBM),
dried distillers grains with solubles (DDGS)), 5 porcine by-products (spray-dried
plasma, purified plasma, intestinal mucosa, meat and bone meal and red blood
cells (RBCs)), 3 vitamin/trace mineral (VTM) mixes (sow, nursery, finishing), 2
fat sources (choice white grease and soy oil), 3 synthetic amino acids (lysine
HCL, D/L methionine, threonine), as well as limestone and dry choline chloride.
Complete feed and stock PEDV served as controls. Thirty grams of each ingredient
were inoculated with 2 mL PEDV. A matched set of samples were treated with the
formaldehyde-based liquid antimicrobial SalCURB(r) (LA). All samples (n = 320)
were stored outdoors under winter time ambient conditions for 30 days. Samples
were submitted on 1, 7, 14 and 30 days post-inoculation (DPI) and tested by PCR
and virus isolation (VI). All VI-negative samples were tested by swine bioassay.
Viable PEDV was detected by VI or swine bioassay at 1, 7, 14 and 30 DPI from SBM,
DDGS, meat & bone meal, RBCs, lysine HCL, D/L methionine, choice white grease,
choline chloride, complete feed and stock virus control and at 7 DPI in limestone
and at 14 DPI in threonine. Supplementary testing of complete feed and SBM
indicated viable virus out to 45 and 180 DPI, respectively. All other samples
were negative by VI and bioassay. In contrast, treatment with LA inactivated PEDV
across all ingredients on 1 DPI and induced RNA reduction over time. CONCLUSIONS:
Under the conditions of this study, PEDV viability in feed was influenced by
ingredient with extended survival in SBM. Furthermore, LA treatment rendered
virus inactive, independent of ingredient type.
PMID- 28405417
TI - Water palatability, a matter of taste.
AB - BACKGROUND: The aim of this trial was to test whether the temperature or
additives of the drinking water affected water uptake by nursery pigs. We
designed a repeated 4 * 4 Latin Square to control for confounding factors such
as; carry-over effects, learning of a preferential taste, daily variation within
groups and regular increase of uptake over a day due to diurnal drinking
patterns. Water types tested were control water (A); warm water (33 degrees C);
(B); organic acid additive 1 (C), and organic acid additive 2 (D). RESULTS: The
piglets drank more of water C than of control water (A). The uptake of water D
was marginally higher than control water (A). There was no difference in uptake
of water B and A. However, a learning effect was observed resulting in increasing
amounts of water type C and D taken up over the four consecutive days. A carry
over was not fully prevented as pigs always consumed less during the second hour
and water D was consumed less during the fourth and final hourly observation
period each day. CONCLUSIONS: The experimental design can be used in future
trials for evaluation of the water uptake and preference of water additives for
pigs. The tested commercial organic acid additives did not adversely affect water
uptake of drinking water, water uptake increased instead.
PMID- 28405418
TI - Porcine epidemic diarrhoea: new insights into an old disease.
AB - Porcine epidemic diarrhea (PED) is an enteric disease in swine caused by an
alphacoronavirus. It affects swine of all ages causing acute diarrhoea and can
lead to severe dehydration and death in suckling piglets. Being recognized for
the first time in Europe and Asia during the seventies and the eighties,
respectively, it has remained a relevant cause of diarrhea outbreaks in Asia for
years and to the present. It has become a major concern in swine production since
2013 when the virus was detected for first time in the USA and in other American
countries causing a high number of pig deaths and significant economic losses.
The present review aims at approaching the reader to the state of the art of PED
giving answer to some of the most recent questions which have arisen related to
this disease.
PMID- 28405419
TI - Providing supplementary, artificial milk for large litters during lactation:
effects on performance and health of sows and piglets: a case study.
AB - BACKGROUND: One possible way to support raising large litter sizes in pigs is to
offer supplementary, artificial milk ad libitum in the farrowing pen in addition
to the sow's milk. In order to evaluate the potential use of this method and its
effects on performance and health, supplemented (n = 60) and control sows (n =
60) with their litters were tested over 15 batches in one herd during one year.
In the supplemented group (SG), piglets had access to supplementary milk in
addition to sow's milk from their 2nd day of life until weaning (day 27). The
litters of SG sows were adjusted to contain as many piglets as the sow had
functional teats, whereas in the control group (CG), piglets were set to the
number of functional teats minus one, due to animal welfare reasons. CASE
PRESENTATION: With supplementary milk provision, the weaning of large litters was
achieved without any negative impacts on performance and health. On average, 13.5
and 12.4 piglets were weaned in SG and CG, respectively (P < 0.05). While average
weaning weights (SG: 7.8 kg v. CG: 7.8 kg; P > 0.05) and average daily weight
gain of the piglets (SG: 0.25 kg v. CG: 0.25 kg; P > 0.05) did not differ, total
litter weight was consequently higher in SG than in CG (104.9 kg v. 96.7 kg; P <
0.001). The average milk replacer intakes were 1.1 kg milk powder per day and
batch, and varied significantly between the "warm" and "cold" seasons (1.5 v. 0.9
kg milk powder per batch and day; P < 0.001). No significant differences in the
mortality rate or the occurrence of diarrhoea were detected in the piglets of
both SG and CG (P > 0.05). With regard to documented medical treatments, facial
lesions were treated less frequently in piglets of SG (46 v. 32 treatments; P <
0.05). There was no effect of supplementary milk on the loss of body weight,
backfat thickness and body condition score of the sows (P > 0.05). CONCLUSIONS:
To summarise, in the presented case offering ad libitum supplementary, artificial
milk supported the sow in raising large litters by compensating possible negative
impacts of high piglet numbers on the weight gain of piglets and the body
condition of the sows.
PMID- 28405420
TI - Behaviour of fattening pigs fed with liquid feed and dry feed.
AB - BACKGROUND: Facilities for fattening pigs offer limited possibilities for
exploration and wet feeding systems, where the pigs drink the food instead of
eating it, have expanded on behalf of dry feeding systems. As little has been
made to evaluate liquid feeding from the point of view of the pigs, the aims of
this study were to compare behaviour in general and behaviour at feeding in
particular of fatteners offered dry or wet feed. The study was carried out in an
integrated herd with age segregated rearing of pigs and access to both feeding
systems in the fattening units. Apart from the feeding system, the pens were
identical and they were managed by the same staff. Pigs were allocated to the
fattening units at 20 kg body weight and their behaviour was studied through web
cameras during day hours (07.00 to 19.00). RESULTS: Pigs performed well in both
systems, but differed in behaviour. Fattening pigs offered dry feed spent longer
time (P < 0.001) eating at every feeding occasion. They also expressed fewer
regroupings during the first week (P < 0.001) when the social rank not yet was
established. Pigs fed liquid feed regrouped during the effective eating time,
while pigs fed dry feed regrouped when the first pig already had left the through
which rather reflected seeking for leftover feed. Restlessness was rarely
recorded before feeding, but rather frequently afterwards. During week 5-9
restlessness was more frequently recorded among pigs offered wet feed. Pigs
offered liquid feed expressed unwanted behaviour in terms of belly-nosing, and
nibbling of ear or tail to a somewhat higher extent than pigs offered dry feed.
In both systems the pigs were occupying themselves with straw when offered, but
only as long as they regarded it as new, i.e., for around 45 min following each
provision. CONCLUSIONS: Pigs performed equivalent in both systems, but from an
animal welfare view we recommend dry feed to growing pigs and suggest that liquid
feed systems ought to be reserved for systems using alternative feed supplies
like whey or other liquid leftovers from the food industry.
PMID- 28405421
TI - Field efficacy study of a novel ready-to-use vaccine against mycoplasma
hyopneumoniae and porcine circovirus type 2 in a Greek farm.
AB - BACKGROUND: The primary objective of this study was to assess the efficacy, under
field conditions, of a novel ready-to use Mycoplasma hyopneumoniae (M hyo) and
Porcine circovirus type 2 (PCV2) combination vaccine given to piglets as one
vaccination (1-shot) at 3 weeks of age. The study was carried out according to a
controlled, randomised, and blinded design in a Greek pig herd with clinical M.
hyo and subclinical PCV2 infection. Moreover, based on serology at the time of
vaccination, the average PCV2 titre was 9.15 log2 and represented the level of
maternally derived antibodies (MDA). In total 602 healthy suckling piglets,
originating from 4 weekly farrowing batches were allocated randomly, within
litters, to one of two groups. The pigs in one group were vaccinated with the
test product and the other pigs were injected with saline. RESULTS: Vaccination
significantly reduced lesions of craneo-ventral pulmonary consolidation in
vaccinated group [expressed as lung lesion score (LLS)] (Mixed model ANOVA: p <
0.0001). The mean LLS was 17.1 in the controls and 10.6 in the treatment group,
respectively. The average daily weight gain (ADWG) during the finishing (54 g
better in the treatment group) and whole study period (34 g better in vaccinated
animals) was significantly greater in vaccinated than control pigs. The
vaccinated pigs had a significant reduction of PCV2 viraemia when compared with
the controls. CONCLUSIONS: The test product was considered effective in the face
of average MDA, based on significantly reduced severity of LLS and PCV2 viral
load, as well as improved ADWG in vaccinated versus control pigs.
PMID- 28405422
TI - A novel octavalent combined Erysipelas, Parvo and Leptospira vaccine provides
(cross) protection against infection following challenge of pigs with 9 different
Leptospira interrogans serovars.
AB - BACKGROUND: In the present study the efficacy and cross protection of a novel
ready-to-use combination vaccine, Porcilis(r) Ery + Parvo + Lepto, against swine
leptospirosis, was investigated. The octavalent vaccine contains inactivated
antigens of Erysipelothrix rhusiopathiae, Parvovirus and 6 Leptospira interrogans
sensu lato strains of serogroups Canicola, Icterohaemorrhagiae, Grippotyphosa,
Australis (Bratislava), Pomona and Tarassovi. In this study ninety pigs were
vaccinated twice with Porcilis(r) Ery + Parvo + Lepto at six and ten weeks of age
and ninety age and source-matched animals served as unvaccinated control. Two
weeks after booster vaccination, groups of vaccinated and control pigs (ten pigs
per group) were challenged with fresh virulent cultures of either of the nine
different challenge strains. Compared to the vaccine strains the challenge
strains were heterologous strains of the same serovar or of a different serovar
within the same serogroup. The challenge strains tested were of serovar Canicola,
Icterohaemorrhagiae, Copenhageni (serogroup Icterohaemorrhagiae), Grippotyphosa,
Bananal/Liangguan (serogroup Grippotyphosa), Pomona, Tarassovi and Vughia
(serogroup Tarassovi). RESULTS: After the different challenges most control
animals became leptospiraemic for 2-7 days. The vaccinated pigs remained blood
culture negative except for two animals after serovar Icterohaemorrhagiae and two
animals after serovar Tarassovi challenge which became leptospiraemic for only 1
day. The incidence of Leptospiraemia (as determined by blood culture) was
significantly less in vaccinates compared to the controls after all challenges.
The vaccine also prevented renal infection and urinary shedding after serovar
Canicola challenge. The other serovars did not induce detectable renal infection
or urinary shedding. CONCLUSION: The present study demonstrates that the new
combination vaccine Porcilis(r) Ery + Parvo + Lepto induces significant (cross)
protection against nine different serovars within the serogroups Canicola,
Icterohaemorrhagiae, Grippotyphosa, Australis (Bratislava), Pomona and Tarassovi.
PMID- 28405424
TI - Probability of introducing porcine epidemic diarrhea virus into Danish pig herds
by imported spray-dried porcine plasma.
AB - BACKGROUND: Porcine epidemic diarrhea virus (PEDV) has never been reported in
Denmark, but it has been found in Europe, Asia and North America. Ultimately,
PEDV has been associated with devastating outbreaks in pig farms. We developed a
stochastic simulation model to carry out a quantitative risk assessment and to
estimate the annual probability (PPlasma) of introducing PEDV into the Danish pig
population, by imported spray-dried porcine plasma (SDPP). The model was based on
information from literature and Danish feed companies. Moreover testing the batch
of raw blood (before the spray-drying) was considered as potential risk
mitigation measure in the future. RESULTS: The median PPlasma was 0.2 % (90 %
P.I.: 0.003 %; 2.6 %). Hence, the annual probability of introducing PEDV into the
Danish pig population by imported SDPP appeared very low, and on average at least
one introduction each 500 years - corresponding to 1/0.002 - could be expected.
However, if PEDV survived the spray-drying process and storage was insufficient
to completely remove the remaining viable virus (e.g. due to storage at low
environmental temperatures during a short time period) the PPlasma was 4.7 %
(0.06 %; 57.4 %). In that case, on average, at least one PEDV introduction each
21 years could be expected. This probability could be reduced to 0.3 % (0.004 %;
6.0 %) if the raw batch of blood could be tested before drying (corresponding to
at least one introduction each 333 years on average). CONCLUSIONS: This study
provides preliminary and important information on the probability of introducing
PEDV into the Danish pig population by use of SDPP. Currently PED is not a
notifiable disease in the EU and uncertainty was present in our estimates due to
possible underreporting in EU Member States, from which SDPP is imported into
Denmark. In the future, PED might become a notifiable disease, and in such a
case, new knowledge could become available on its epidemiology. Moreover, SDPP
could be imported more safely if: producers find a way to substantiate freedom
from disease (at least) in herds delivering blood for SDPP, the batch of blood
tests negative for PEDV and conditions for processing/storage required by the
international laws are respected.
PMID- 28405423
TI - Porcine circovirus 2 immunology and viral evolution.
AB - Porcine circovirus 2 (PCV2) has and is still causing important economic losses to
pig industry. This is due to PCV2-systemic disease (PCV2-SD), formerly known as
postweaning multi-systemic wasting syndrome (PMWS), which increases mortality
rates and slows down the growth of the animals, as well as other conditions
collectively included within the so-called porcine circovirus diseases (PCVD).
PCV2-SD affected pigs are considered to be immunosuppressed, with severe
lymphocyte depletion and evidence of secondary infections. However, PCV2-infected
pigs not developing the disease are able to mount humoral and cellular immune
responses and clear the virus or limit the infection. On the contrary,
insufficient amounts of neutralizing antibodies have been linked to increased
PCV2 replication, severe lymphoid lesions and development of PCV2-SD. Central
role in controlling PCV2 infection are played by the antigen specific memory T
cells. These cells persist long term post-infection or vaccination and are able
to expand rapidly after recall antigen recognition. Most farms in the main pig
producing countries are applying vaccination against PCV2 to prevent the disease
and improve the farm performance. Vaccines do not induce sterilizing immunity and
PCV2 keeps on circulating even in farms applying vaccination. This, together with
the high mutation rate of PCV2, world-wide fluctuations in the genotype dominance
and emergence of novel genetic variants, warrant close molecular survey of the
virus in the field.
PMID- 28405425
TI - Performance of ELISAs for detection of antibodies against porcine respiratory and
reproductive syndrome virus in serum of pigs after PRRSV type 2 live vaccination
and challenge.
AB - BACKGROUND: The aim of the study was to evaluate the performance of different
newly developed and/or commercially available ELISAs for detection of PRRSV
specific antibodies. Consequently, ten PRRSV negative piglets (group V) were
vaccinated with a PRRSV type 2 vaccine. Blood samples were taken before as well
as seven, 21 and 42 days after vaccination. At day 42 after vaccination (day 0 of
the study) all of the piglets from group V and 10 non-prevaccinated PRRSV
negative piglets (group N) were challenged with an HP PRRSV type 2 field strain.
Blood samples were taken before and at days 3, 7, 10, 14, 21 and 28 after
challenge. The success of vaccination and challenge was measured with RT qPCR.
All serum samples were tested with six ELISAs for detection of PRRSV antibodies.
Three of them are nucleocapsid-based, two use a glycoprotein extract and one uses
inactivated whole virus as antigen. The specificity of the ELISAs was evaluated
using 301 serum samples of piglets from PRRSV negative herds. RESULTS: The
piglets from group V tested positive by RT qPCR at day 7 after vaccination and
all piglets tested positive at day 3 after challenge. PRRSV specific antibodies
were seen with all nucleocapsid-based ELISAs from day 21 after vaccination
onwards in group V and from day 10 after challenge in group N. The glycoprotein
based ELISAs detected antibodies from day 42 after vaccination (group V) and day
21 after challenge (group N). The agreement according to kappa-coefficient was
almost perfect. The glycoprotein-based ELISAs were able to distinguish PRRSV type
2, although with some cross reactions. Regarding specificity, the ELISAs
performed differently (specificity between 97.4 % and 100 %), whereas most of the
ELISAs with higher sensitivity had a slightly lower specificity. CONCLUSIONS: All
tested ELISA were able to detect PRRSV antibodies in the serum of pigs vaccinated
with a PRRSV type 2 vaccine and after challenge with an HP PRRSV type 2 field
strain. The onset on antibody detection differed, depending on the type of
antigen used in the ELISAs. Most of the ELISAs with a higher sensitivity had a
lower specificity.
PMID- 28405426
TI - African swine fever: a global view of the current challenge.
AB - African Swine Fever (ASF) is an important contagious haemorrhagic viral disease
affecting swine whose notification is mandatory due to its high mortality rates
and the great sanitary and socioeconomic impact it has on international trade in
animal and swine products. This disease only affects porcine species, both wild
and domestic, and produces a variety of clinical signs such as fever and
functional disorders of the digestive and respiratory systems. Lesions are mainly
characterized by congestive-haemorrhagic alterations. ASF epidemiology varies
significantly between countries, regions and continents, since it depends on the
characteristics of the virus in circulation, the presence of wild hosts and
reservoirs, environmental conditions and human social behaviour. Furthermore, a
specific host will not necessarily always play the same active role in the spread
and maintenance of ASF in a particular area. Currently, ASF is endemic in most
sub-Saharan African countries where wild hosts and tick vectors (Ornithodoros)
play an important role acting as biological reservoirs for the virus. In Europe,
the disease has been endemic since 1978 on the island of Sardinia (Italy) and
since 2007, when it was first reported in Georgia, in a number of Eastern
European countries. It is also endemic in certain regions of the Russia
Federation, where domestic pig and wild boar populations are widely affected. By
contrast, in the affected eastern European Union (EU) countries where ASF is
currently as epidemic, the on-going spread of the disease affects mainly wild
boar populations located in restricted areas and, to a much less extent, domestic
pigs. Unlike most livestock diseases, no vaccine or specific treatment is
currently available for ASF. Therefore, disease control is mainly based on early
detection and the application of strict sanitary and biosecurity measures.
Epidemiology of ASF is very complex by the existence of different virus
circulating, reservoirs and a number of scenarios, and the on-going spread of the
disease through Africa and Europe. Survivor pigs can remain persistently infected
for months which may contribute to virus transmission and thus the spread and
maintenance of the disease, thereby complicating attempts to control it.
PMID- 28405428
TI - Managing undocked pigs - on-farm prevention of tail biting and attitudes towards
tail biting and docking.
AB - BACKGROUND: Tail biting is a common and serious welfare problem in pig
production, causing large economical losses. Tail docking is performed routinely
in most EU countries to reduce the tail biting risk. However, tail docking is
painful, and does not prevent tail biting totally. The risk factors behind tail
docking are multifactorial and most analyses are based on studies using
biological or epidemiological approaches. There is very little information
available on how producers deal with tail biting on-farm. There are also no
studies on the attitude of producers towards tail docking and tail biting in
systems with long-tailed pigs. We aimed to study how farmers rate the efficiency
of different measures for preventing and intervening with tail biting, when tail
docking is not allowed. Furthermore, we investigated the attitudes of Finnish
farmers to tail docking and tail biting. RESULTS: Respondents scored feeding
related issues to be most important for prevention of tail biting, identifying
and removing the biting pig as most important intervention measures, and straw as
the most important manipulable material when preventing tail biting. Tail biting
was not perceived as a very serious problem by over 70 % of the respondents, even
though docking is not allowed, and was reported to occur close to a level which
was also considered acceptable by the respondents. Most respondents did not think
it is probable they would raise tail docked pigs if it were possible, but about
21 % probably would. CONCLUSIONS: In comparison with other authors' findings, the
ranking of importance of risk factors for tail biting differs between scientists
and farmers, and between farmers in different cultures of pig production. In
addition, the attitude towards tail biting and tail docking appears to be very
different in producers with different experiences of tail docking. These results
indicate that a scientist-farmer dialogue, as well as international communication
is important when trying to reduce the risk of tail biting, and subsequently the
need for tail docking.
PMID- 28405427
TI - An evaluation of gonadotropin-releasing hormone analogue administered to gilts
and sows on subsequent reproductive performance and piglet birth weight.
AB - BACKGROUND: The present study investigated the effect of peforelin (Maprelin(r)),
a gonadotropin-releasing hormone (GnRH) analogue, administration in gilts,
primiparous and pluriparous sows in a high productive farm on sow reproductive
performance and piglet quality at birth. METHODS: In a 400 sow herd, gilts,
primiparous and pluriparous sows were randomly allocated to 2 groups: peforelin
treated (peforelin = P-group) or no treatment (control = C-group). Animals were
injected 48 h after the last altrenogest treatment (gilts) or 24 h post weaning
(sows). Weaning-to-estrus interval (WEI), estrus rate (ER), farrowing efficiency
index (FEI), farrowing rate (FR), number of total (TBP), live (LBP) and stillborn
piglets (SBP), mummies (MM) and live piglet index (LPI) were assessed and
compared between treatment groups. To assess piglet quality at birth, 6033
piglets from 426 litters were weighed individually within 24 h after birth (BW;
birth weight). RESULTS: No significant difference between treatment groups could
be observed for WEI, TBP, LBP, SBP and MM. The ER was significantly (P = 0.0119)
higher (93.2 %) in the P-group as compared to the C-group (87.2 %). Peforelin
treatment did not affect farrowing rate. Both FEI and LPI were significantly (P =
0.0078) better in the P-group as compared to the C-group. Overall, no effect of
peforelin treatment on piglet birth weight could be observed, although specific
subcategories (1st parity and older (5+ parity) sows) did have a significant
impact of treatment on birth weight. During late summer (August-September) all
treated gilts and sows took advantage from peforelin treatment with a significant
improvement of piglet birth weight. CONCLUSION: Peforelin treatment had a
significant impact on ER, FEI and LPI. Moreover, piglet birth weight improved for
specific sow subcategories (1st parity and older sows) and for all gilts and sows
during the late summer infertility period.
PMID- 28405429
TI - Novel analytic tools for the study of porcine reproductive and respiratory
syndrome virus (PRRSv) in endemic settings: lessons learned in the U.S.
AB - Since its emergence in the late 1980's, the porcine reproductive and respiratory
syndrome virus (PRRSv) has posed a significant challenge to the pig industry
worldwide. Since then, a number of epidemiological tools have been created to
support control and eventual elimination of the disease at the farm and regional
levels. Still, many aspects of the disease dynamics are yet-to-be elucidated,
such as what are the economically optimal control strategies at the farm and
regional level, what is the role that the voluntary regional control programs may
play, how to optimize the use of molecular tools for surveillance and monitoring
in infected settings, what is the full impact of the disease in a farm, or what
is the relative contribution of alternative transmission routes on the occurrence
of PRRSv outbreaks. Here, we summarize a number of projects demonstrating the use
of novel analytical tools in the assessment of PRRSv epidemiology in the United
States. Results presented demonstrate how quantitative analysis of routinely
collected data may help in understanding regional epidemiology of PRRSv and to
quantify its full impact, and how the integration of phylodynamic methods as a
standard tool for molecular surveillance of PRRSv might help to inform control
and prevention strategies in high-risk epidemiological situations. Ultimately,
these tools will help to support PRRSv control at farm and regional levels in
endemically infected settings.
PMID- 28405430
TI - Influence of spray dried porcine plasma in starter diets associated with a
conventional vaccination program on wean to finish performance.
AB - BACKGROUND: Conventional vaccination programs using a single injection of a
combined vaccine against porcine circovirus type 2 (PCV2) and Mycoplasma
hyopneumoniae (MHYO) can promote a strong immune response that reduces feed
intake for 24 to 48 h post injection. Often such vaccines are given around the
time of weaning during a critical stress period in which feed intake is already
compromised. Spray dried porcine plasma (SDPP) is a protein source used in
starter diets that increases post-weaning feed intake of pigs. The objectives of
this study were to determine the effects of a conventional vaccination program
along with feeding SDPP in a starter diet on antibody development and wean to
finish performance of pigs. RESULTS: Pigs fed the starter diet with SDPP had
improved body weight, average daily weight gain and average daily feed intake
during the initial 14 d after weaning along with improved feed efficiency during
the initial 7 d after weaning and these responses were independent of
vaccination. Vaccination at 3 d after weaning had no significant effect on
performance during the initial 14 d after weaning. Cumulative mortality was
reduced for pigs fed the starter diet with SDPP, while vaccinated pigs had
reduced mortality from d 48 to 145. Both vaccinated pigs and those fed the
starter diet with SDPP had heavier carcass weight. One pig per pen was challenged
with PCV2 at d 63. A higher percentage of vaccinated pigs were sero-positive for
antibodies against PCV2 and MHYO at d 35, 63 and 78. Antibody values against PCV2
were higher for vaccinated pigs at d 35 and 63, but lower at d 146. Percentage of
positive samples for PCV2 genome in serum was reduced for vaccinated pigs at d
117 and 146. Antibody values against MHYO were increased for vaccinated pigs at d
35, 63 and 78. CONCLUSIONS: Vaccination supported a long term antibody response
against PCV2 and a moderate but weaker antibody response against MHYO for early
finishing pigs challenged with PCV2. Using SDPP in the starter diet along with
vaccination supported the best long-term beneficial effects on survival to market
and carcass weight.
PMID- 28405431
TI - Risk factors for oral antimicrobial consumption in Swiss fattening pig farms - a
case-control study.
AB - BACKGROUND: Antimicrobial consumption in veterinary medicine is of great
importance. Increased awareness by the public and media has led to demands for
decreased use of antimicrobials in pigs. This study aimed to identify risk
factors for regular oral antimicrobial consumption in Swiss fattening pig farms,
and to quantify the amount of antimicrobial active substances administered orally
to pigs at the farm level. RESULTS: A case-control study was performed on 99
fattening farms between May 2014 and January 2015. Seventy-two case farms (with
oral group treatment of antimicrobials in at least 50 % of pigs) and 27 control
farms (with no regular oral group treatment) were visited once during the study.
Data about potential risk factors and antimicrobial consumption were collected by
questionnaire. Antimicrobial consumption was recorded and treatment incidence
(TI) was calculated for all farms over a one year period. Sulphonamides and
tetracyclines were the antimicrobials consumed in the greatest quantity. The
median TI for oral antimicrobial use in the case group was 224.7. In the control
group, the median TI was 0 for oral antimicrobial use, with values ranging from 0
to 140.1. In a multivariable regression model, seven risk factors associated with
regular oral antimicrobial group treatment were identified: mixing pigs from
different suppliers within the same pen, absence of a work protocol that ensures
treating of healthy pigs before sick pigs, distance to next pig farm < 500
metres, external analysis of production parameters, no availability of dirty
visitor boots, the farmer not working on other farms, and no application of
homoeopathic agents. CONCLUSIONS: The results of this study point out the
importance of increasing farmers' awareness of good farming practices and
biosecurity. Important recommendations for decreasing oral antimicrobial
consumption identified by this study include avoiding mixing pigs from different
suppliers in the same pen and strictly handling sick pigs after healthy ones.
Improvements in these areas could enhance the overall health of pigs and thereby
reduce the consumption of antimicrobials on pig farms.
PMID- 28405432
TI - Effect of diet supplementation with chelated zinc, copper and manganese on hoof
lesions of loose housed sows.
AB - BACKGROUND: Hoof lesions are very common among sows and have been associated with
lameness, early removal and compromised welfare and productivity. Although
housing conditions and management can have an external effect on hoof health
status, the role of trace mineral intake is vital in developing hoof structure
and integrity. Therefore, the objective of this study was to investigate the
effect of a diet supplemented with organic complexes of trace minerals (Zn, Cu,
Mn), partly substituting their inorganic form, on hoof lesions of sows in three
Greek swine herds. RESULTS: A total of 518 sows were initially examined for hoof
lesions and their respective severity was scored. For each hoof, the length of
toes and dew claws were evaluated and five anatomical hoof sites, the heel, the
sole, the white line, the wall and the coronary band, were examined for lesions.
Subsequently, the same sows were re-scored after one or two gestations on diets
supplemented with organic trace minerals, partly substituting their inorganic
salt form (organic form of Zn 45 ppm, Cu 14 ppm and Mn 25 ppm of the total 125
ppm of Zn, 15 ppm of Cu and 40 ppm of Mn, respectively). The odds of the higher
versus the lower lesion scores were significantly lower after than before the
inclusion of the organic minerals in sows' diet, for each of the considered foot
sites with the exception of the coronary band, with a distinct effect according
to foot location. Specifically, on rear feet the improvement of hoof lesions was
either smaller (for heel, sole and wall) than on front feet or not significant
(for white line, toe and dew claw length). Additionally, for each foot site and
herd examined, after the inclusion of the organic minerals, there were more sows
with either the same or lower lesion score, with the exception of the toe and the
dew claw length in one of the herds. CONCLUSIONS: Within the specific conditions
in the three studied herds, our findings highlight the role of chelated trace
minerals in sows' hoof health, suggesting an applicable and rewarding
intervention to prevent hoof lesions.
PMID- 28405433
TI - Factors affecting the daily feed intake and feed conversion ratio of pigs in grow
finishing units: the case of a company.
AB - BACKGROUND: The aim of this study was to use mathematical modeling to identify
and quantify the main factors that affect daily feed intake (DFI) and feed
conversion ratio (FCR) in grow-finishing (GF) pig units. We evaluated the
production records of 93 GF farms between 2010 and 2013, linked to a company,
working in a cooperative system, located in western Parana State, Brazil. A total
of 683 batches, consisting of approximately 495,000 animals, were used. Forty
production factors related to the management, health, plant and equipment,
nutrition, genetics and environment were considered. The number of pigs per pen,
type of feeder, origin and sex (the last two variables were combined in the
models) of the animals and initial and final body weights were included in the
final models to predict DFI and FCR (dependent variables). Additionally, the
duration of the GF phase was included for the parameter FCR. All factors included
in the final models had significant effects for both dependent variables.
RESULTS: There was a reduction in DFI (0.04 kg) (P < 0.001) and an improvement in
FCR (6.0 points) (P < 0.001) in batches from pens with less than 20 animals
compared with batches from pens with more than 20 animals. In barns with "other"
feeder types (mostly the linear dump type) different of conical semiautomatic
feeder, a reduction of DFI (0.03 kg) (P < 0.05) and improved FCR (3.0 points) (P
< 0.05) were observed. Batches of barrows from units specialized for producing
piglets (SPU) had higher DFI (approximately 0.02 kg) (P < 0.01) than batches of
females and batches of mixed animals from SPU, and batches of mixed animals from
farms not specialized for piglet production (farrow-to-finish farms). Batches of
females from SPU and mixed batches from SPU had better FCR (5.0 and 3.0 points
respectively) (P < 0.001 and P < 0.001, respectively) than batches of piglets
originating from farrow-to-finish farms. The variables selected for the final
models explained approximately 50 and 64 % of the total variance in DFI and FCR,
respectively. CONCLUSIONS: The models are tools for the interpretation of the
factors related to the evaluated parameters, aiding in the identification of
critical aspects of production. The main parameters affecting DFI and FCR in this
company during the GF period were the number of pigs per pen, the type of feeder
used and the combination origin-sex of the animals.
PMID- 28405434
TI - Lameness in piglets - should pain killers be included at treatment?
AB - BACKGROUND: Joint swelling and lameness are the most obvious and persistent
clinical signs of infectious arthritis in piglets. For a positive treatment
effect of piglets with arthritis, early initiated treatments with antibiotics are
desired. Hitherto pain-reducing drugs have rarely been used within veterinary
medicine, but the potential of non steroid anti-inflammatory drugs (NSAID) are
interesting from an animal welfare perspective. Therefore, the aim of this study
was to compare the long term efficiency of treating lameness with and without
pain relief. Further, the incidences of affected joints in lame piglets were
analysed. RESULTS: In total 415 of the 6,787 liveborn piglets included in the
study were diagnosed with lameness (6.1 %). Around 86 % of these diagnoses took
place during the first 3 weeks of life. There was no difference in the incidence
of lameness between the sexes, but lameness was most commonly diagnosed in the
offspring to old sows (>4 parturitions). Lameness was diagnosed in about every
second litter and on average about two pigs were diagnosed in the affected
litters. The incidence of affected litters as well as affected piglets increased
with ageing of the sows. Treatments with antibiotics solely and in combination
with NSAID improved (P < 0.01 to 0.001) the clinical status from day to day, but
the clinical response did not differ between the two treatment groups. Piglets
that remained healthy were 1.1 and 1.7 kg heavier (P < 0.001) than piglets
diagnosed with lameness at 5 and 9 weeks of age, respectively. There were no
differences in piglet body weights between the treatment strategies at any time.
CONCLUSIONS: The clinical response to penicillin was good. It was neither
improved nor reduced by a concurrent administration of NSAIDs. Nevertheless
NSAIDs may improve the animal welfare due to pain relief. An important finding of
this study was that decreasing pain due to lameness not was negative in a long
term perspective, i.e. reducing pain did not lead to overstrain of affected
joints and no clinical signs of adverse effects were noted. Therefore the use of
NSAIDs ought to be considered to improve the animal welfare, at least in severe
cases.
PMID- 28405435
TI - Evaluation of the relationship between the biosecurity status, production
parameters, herd characteristics and antimicrobial usage in farrow-to-finish pig
production in four EU countries.
AB - BACKGROUND: High antimicrobial usage and the threat of antimicrobial resistance
highlighted the need for reduced antimicrobial usage in pig production.
Prevention of disease however, is necessary to obtain a reduced need for
antimicrobial treatment. This study aimed at assessing possible associations
between the biosecurity level, antimicrobial usage and farm and production
characteristics in order to advice on best practices for a low antimicrobial
usage and maximum animal health and production. A cross-sectional study was
conducted in 227 farrow-to-finish pig herds in Belgium, France, Germany and
Sweden between December 2012 and December 2013. Associations between biosecurity
status, antimicrobial usage, and production parameters were evaluated with
multivariable general linear models, according to an assumed causal pathway.
RESULTS: The results showed that higher antimicrobial usage in sows tended to be
associated with higher antimicrobial usage from birth until slaughter (p = 0.06).
The antimicrobial usage from birth until slaughter was positively associated with
the number of pathogens vaccinated against (p < 0.01). A shorter farrowing rhythm
(p < 0.01) and a younger weaning age (p = 0.06) tended to be also associated with
a higher antimicrobial usage from birth until slaughter whereas a better external
biosecurity (p < 0.01) was related with a lower antimicrobial usage from birth
until slaughter. CONCLUSION: Management practices such as weaning age and
biosecurity measures may be important factors indirectly impacting on
antimicrobial usage. We therefore promote a holistic approach when assessing the
potential to reduce the need for antimicrobial treatments.
PMID- 28405436
TI - Modelling the within-herd transmission of Mycoplasma hyopneumoniae in closed pig
herds.
AB - BACKGROUND: A discrete time, stochastic, compartmental model simulating the
spread of Mycoplasma hyopneumoniae within a batch of industrially raised pigs was
developed to understand infection dynamics and to assess the impact of a range of
husbandry practices. A 'disease severity' index was calculated based on the ratio
between the cumulative numbers of acutely and chronically diseased and infectious
pigs per day in each age category, divided by the length of time that pigs spent
in this age category. This is equal to the number of pigs per day, either acutely
or chronically infectious and diseased, divided by the number of all pigs per all
days in the model. The impact of risk and protective factors at batch level was
examined by adjusting 'acclimatisation of gilts', 'length of suckling period',
'vaccination of suckling pigs against M. hyopneumoniae', 'contact between
fattening pigs of different age during restocking of compartments' and 'co
infections in fattening pigs'. RESULTS: The highest 'disease severity' was
predicted, when gilts do not have contact with live animals during their
acclimatisation, suckling period is 28 days, no vaccine is applied, fatteners
have contact with pigs of other ages and are suffering from co-infections. Pigs
in this scenario become diseased/infectious for 26.1 % of their lifetime.
Logistic regression showed that vaccination of suckling pigs was influential for
'disease severity' in growers and finishers, but not in suckling and nursery
pigs. Lack of contact between gilts and other live pigs during the
acclimatisation significantly influenced the 'disease severity' in suckling pigs
but had less impact in growing and finishing pigs. The length of the suckling
period equally affected the severity of the disease in all age groups with the
strongest association in nursery pigs. The contact between fatteners of different
groups influenced the course of infection among finishers, but not among other
pigs. Finally, presence of co-infections was relevant in growers and finishers,
but not in younger pigs. CONCLUSION: The developed model allows comparison of
different prevention programmes and strategies for controlling transmission of M.
hyopneumoniae.
PMID- 28405437
TI - Production parameters and pig production cost: temporal evolution 2010-2014.
AB - BACKGROUND: The assessment of the cost of production and the relative weight of
the different production parameters is very important in pig farming. The goals
of the present work were 1) to describe reliable reference values for production
parameters and pig production cost from 2010 to 2014, 2) to describe their
temporal evolution and 3) to determine the influence of the pig company size on
them. Between 61 and 107 pig production companies from Spain were included in
this study from 2010 to 2014. These companies sent data on feed consumption,
number of pig produced, expenses and census every month. Sip consultors SL
standardized collected data and calculate cost and production parameters to
obtain values comparables between the different pig production companies. The
collected data each month were merged to obtain a yearly average value taking
into account the pig production flow each month. A suitable statistical analysis
was carried out to tackle the goals. RESULTS: The production performance has been
continuously improving in the piglet production and fattening phase from 2010 to
2014. Thus, the number of piglets by sow and year will increase 0.5 pigs by year
and the total feed conversion rate will decrease approximately 0.03 kg feed/kg
gain by year in the future if the same tendency continues. However, feed price
has been steadily increasing from 2010 to 2012 and decreasing afterwards and the
total cost per kilogram produced has followed a similar pattern. This result
highlights the relevance of the feed price in the final cost in spite of
continuous improvement in production performance across years. Finally, pig
company size affected most of the production parameters studied. Thus, the best
technical parameters were obtained for companies with less than 5000 sows.
However, the opposite tendency is observed for feed price where the highest value
was observed for the smallest companies. CONCLUSIONS: Pig production parameters
have generally improved in the last five years but this improvement did not
directly imply a reduction in pig production cost due to the high feed prices
during the period 2010-2013.
PMID- 28405438
TI - Modified-live PRRSV subtype 1 vaccine UNISTRAIN(r) PRRS provides a partial
clinical and virological protection upon challenge with East European subtype 3
PRRSV strain Lena.
AB - BACKGROUND: Western European porcine reproductive and respiratory syndrome virus
(PRRSV) strains cause limited and mild clinical signs whereas more virulent
strains are circulating in Eastern Europe. The emergence of such highly virulent
strains in Western Europe might result in severe clinical problems and a
financial disaster. In this context, the efficacy of the commercial modified-live
PRRSV subtype 1 vaccine UNISTRAIN(r) PRRS was tested upon challenge with the East
European subtype 3 PRRSV strain Lena. RESULTS: The mean duration of fever was
shortened and the number of fever days was significantly lower in vaccinated pigs
than in control pigs. Moreover, a lower number of vaccinated animals showed
fever, respiratory disorders and conjunctivitis. The mean virus titers in the
nasal secretions post challenge (AUC) were significantly lower in the vaccinated
group than in the control group. The duration of viremia was slightly shorter
(not significantly different) in the vaccinated group as compared to the control
group. CONCLUSIONS: Vaccination of pigs with the modified-live vaccine
UNISTRAIN(r) PRRS provides a partial clinical and virological protection against
the PRRSV subtype 3 strain Lena.
PMID- 28405439
TI - Preliminary findings on the effect of the pig appeasing pheromone in a slow
releasing block on the welfare of pigs at weaning.
AB - The pig appeasing pheromone (PAP) applied in spray has shown to be effective in
reducing the frequency of aggression and the stress response of young and adult
pigs under experimental conditions. This preliminary experiment investigates the
effect of the PAP in a slow releasing block on the behaviour and skin lesions of
weaners after mixing on a commercial farm. Two identical rooms containing six
replicates per treatment of a commercial weaner building were used. There were
two treatments (PAP block and Control) and each room contained one treatment. In
the PAP treatment, the day before weaning and after washing and disinfection, two
PAP blocks (1 block / 20 m2) were placed hanging on top of the pens. Six hours
after mixing, there was a significant effect of the PAP block treatment on the
occurrence of social negative behaviour (PAP mean; median [95 % CI] for median =
3.6; 2.7 [1.5-5.4] % vs. Control 8.3; 8.7 [6.1-11.3] % P = 0.003, social positive
behaviour (PAP 5.5; 5.1 [4.5-6.8] % vs. Control 1.4; 1.3 [0-2.8] % P = 0.02),
feeding (PAP 9.1; 7.4 [5.5-16.5] % vs. Control 1.6; 0.0 [0-6.1] % P = 0.02,
drinking (PAP 3.1; 2.9 [2.5-3.9] % vs. Control 0.8; 0.5 [0-1.7] % P = 0.04) as
well as on the sitting position (PAP 1.2; 0.9 [0-2.4] % vs. Control 4.1; 4.2 [2.1
6.0] % P = 0.02). Except for social positive behaviour (PAP 5.6; 6.0 [3.9-7.5] %
vs. Control 2.9; 2.8 [1.6-4.2] % P = 0.02) those differences were not significant
24 h post-mixing anymore. The prevalence of wounded animals was not significantly
different between treatments. The PAP in block form may be a promising tool to
reduce food neophobia and aggression after mixing. Still, further research is
needed to increase the effect of the PAP block over time under commercial farming
conditions.
PMID- 28405440
TI - A comment on the paper 'A comparison between lesions found during meat inspection
of finishing pigs raised under organic/free-range conditions and conventional
indoor conditions' by Alban et al. 2015.
AB - This is a critical comment on a paper published in Porcine Health Management in
2015, presenting a comparison between lesions from meat inspection at one
abattoir on slaughter pigs classified in to two different production forms:
organic/free-range conditions and conventional indoor conditions. The conclusion
made by the paper that 13 lesion types has a higher prevalence in organic/free
range pigs and 4 lesion types occurred less frequently in organic/free-range
finishers compared to conventional finishers is correct except that 5 (instead of
4) lesion types occurred less frequently in organic/free-range finishers.
However, these five types of lesions represent 74 % of all lesions recorded among
conventional indoor, conventional free-range and organic pigs in one slaughter
house from October 1 2012 to September 26 2013.
PMID- 28405441
TI - Reproduction of group-housed sows.
AB - The sow is a social animal in her behavior throughout the reproductive cycle. An
exception to her preference for being a part of a social group occurs one to two1
2 d days prior to farrowing, when she separates from her group and seeks for
isolation in order to build up a nest. She then spends the first week or two with
her piglets, mainly in the nest. After this short period of separation of 1-2
weeks, she brings her litter with her and rejoins the group. In modern intensive
pig production, the sow is often restricted to an individual cage for lactation
and, in many European countries, she may still spend additional periods in stalls
during pregnancy. In the intensive production, isolation of the sow from the rest
of the group is therefore a relatively long period of six to ten6-10 weeks, which
creates a challenge for the social memory of the sow. While grouping of sows
during lactation is an interesting option, until now this is encountered mostly
in organic or otherwise extensive farming systems, such as outdoor farming.
However, the present society is asking for more animal friendly models of
production and there appears to be more need for studies of group housing issues
during lactation. Grouping of sows after weaning causes stress, which imposes
risks for fertility. Thus, timing of grouping is probably very critical. It is
well documented that the embryonic period of the pregnancy, lasting up to Day 35,
is more vulnerable for loss of pregnancy than the subsequent fetal period. There
are indications that stress of grouping may cause some harm to vitality
parameters of blastocysts already while at the site of fertilization in the
oviduct. Later on, during the critical periods of maternal recognition of
pregnancy, endocrinological models testing maintenance of pregnancy suggest that
chronic stress lasting for more than two2 days may cause abortion and loss of the
whole litter. However, the sow may be resistant, in terms of her reproductive
function, to acute stress lasting for hours or up to a day. In conclusion,
grouping of sows during lactation may be of interest in the future. At present,
issues of group housed sows after weaning and early pregnancy seem to be of most
practical relevance. Chronic stress of sows lasting for more than two2 days may
lead to loss of the whole litter.
PMID- 28405442
TI - Spray dried plasma as an alternative to antibiotics in piglet feeds, mode of
action and biosafety.
AB - The use of growth promoting and therapeutic antibiotics in piglet feed has been a
concerning subject over the last few decades because of the risk of generating
antimicrobial resistance that could be transferred to humans. As a result, many
products have been proposed as potential alternatives to the use of antibiotics,
and among these, spray dried plasma is considered one of the most promising.
However, there have been concerns about its biosafety, particularly during
periods of emergence or re-emergence of swine diseases in different regions of
the world, such as the recent porcine epidemic diarrhea virus outbreak in North
America. The objectives of this paper are to review recent publications about the
use of spray dried plasma as an alternative to antibiotics in weaned pig diets,
the possible mechanisms of action of spray dried plasma, and the existing
evidence related to the biosafety of spray dried animal plasma. Particular
attention is given to studies in which spray dried plasma has been directly
compared to antibiotics or other alternative antimicrobial products. Several
studies on the possible modes of action for spray dried plasma, such as
preservation of gut barrier function or modulation of the immune response, are
also reviewed. Finally, the paper focuses on the review of the existing studies
on the risks of disease transmission with the use of spray dried plasma from
porcine origin. Overall, spray dried plasma is a promising alternative to in-feed
antimicrobials for piglets, particularly during the early stages of the post
weaning phase. Additionally, there is enough evidence to support that commercial
spray dried porcine plasma is a safe product for pigs.
PMID- 28405443
TI - Impact of group housing of pregnant sows on health.
AB - Group housing of sows during gestation is mandatory in the EU since 2013.
Compared to housing in individual crates, group housing allows the animals to
express normal activity and behavior. The present paper discusses the impact of
group housing on health, with emphasis on lameness, aggression and possible
spread of infectious diseases. The prevalence of lameness is generally higher in
sows housed in group than in sows housed individually. Floor space per sow, group
size, pen design and flooring are the main factors of group housing involved in
lameness development. Especially floor characteristics are important, and
particular attention should be paid to the type, building material and quality of
the floor, hygiene and the use of bedding such as straw or rubber mats.
Aggression between sows is another critical issue in group housing systems. It
occurs predominantly because of competition for access to a limited resource, or
to establish a social hierarchy. Key factors to prevent aggression in group
housing include gradual familiarization of unfamiliar animals, sufficient space
and pen structure during initial mixing, minimizing opportunities for dominant
sows to steal food from subordinates, provision of a good quality floor,
environmental enrichment and use of straw bedding. Very scarce evidence-based
information is available on the relationship between group housing and infectious
disease. Compared to individual housing, sows in group housing have more nose-to
nose contact, and they have more oral contact with feces and urine. These factors
could contribute to a higher or faster transmission of pathogens, but so far,
there is no evidence showing more disease problems in group housing systems. In
conclusion, in group housing systems, particular attention should be paid to
prevention of lameness and aggression. Management is crucial but also feeding
strategies, floor and bedding, and design of housing are very important as
relatively minor adjustments may exert major effects on the animals.
PMID- 28405444
TI - Antimicrobial use in Swedish farrow-to-finish pig herds is related to farmer
characteristics.
AB - BACKGROUND: Antimicrobial resistance is an increasing problem and reducing AM use
is critical in limiting its severity. The underlying causes of antimicrobial use
at pig farm level must be understood to select effective reduction measures. We
previously showed that antimicrobial use on Swedish pig farms is comparatively
low but varies between farms, although few farms are high users. In the present
survey of a convenience sample of 60 farrow-to-finish herds in Sweden, we
investigated farmers' attitudes to antimicrobials and the influence of
information provided by veterinarians about antimicrobial resistance. Farm
characteristics were also recorded. We had previously quantified antimicrobial
use for different age categories of pigs during one year, as well as external and
internal biosecurity. Risk factors based on hypothetical causal associations
between these and calculated treatment incidence (TI) for the different age
categories were assessed here in a linear regression model. RESULTS: There were
no significant associations between biosecurity and TI for any pig age category.
Increasing farmer age was associated with higher TI for suckling piglets and
fatteners. For suckling piglets, the age group with the highest frequency of
treatment, TI was also significantly associated with farmer and education of the
staff, where female farmers, and university educated staff was associated with a
higher TI. Larger farms were associated with a higher TI in fatteners.
CONCLUSIONS: In the investigated Swedish pig farms, factors that influenced
antimicrobial usage were more related to characteristics of the individual farmer
and his/her staff than to biosecurity level, other management factors or farmers'
attitudes to antimicrobials.
PMID- 28405445
TI - Clinical problems due to encephalomyocarditis virus infections in two pig herds.
AB - BACKGROUND: Infections with encephalomyocarditis virus may cause myocarditis and
sudden death in young pigs and reproduction disorders in sows. The presence of
encephalomyocarditis virus infected rodents is considered a major risk factor for
transmission of the virus to pigs. There is currently no effective treatment.
Tightening up biosecurity, applying effective rodent control and reducing stress
are the main control measures. CASE PRESENTATION: Two farrow-to-finish herds
suffering from problems with sudden death are presented. In herd A, suckling
piglets from 3 to 12 days old were dying acutely whereas in herd B, piglets at
the end of the nursery period (8-10 weeks) were showing identical problems. A
presumptive diagnosis of encephalomyocarditis virus infection was made because
typical lesions were observed in some of the affected pigs. These lesions were
not always present in pigs dying acutely or in some cases the lesions were very
subtle. Therefore other causes had to be ruled out based upon clinical history,
clinical signs and diagnostic tests. A conclusive diagnosis was finally
established by showing encephalomyocarditis virus in heart tissue using
conventional gel-based polymerase chain reaction tests. The real-time PCR test
that gave initially negative result was further optimized to avoid false negative
results. CONCLUSIONS: Typical lesions are not always present in piglets infected
with encephalomyocarditis virus, indicating the importance of examining multiple
animals. Problems in suckling piglets may occur in affected herds without
reproductive problems in sows. Transmission routes of EMCV in swine are not fully
understood. A stand-empty period following thorough cleaning and disinfection is
recommended for controlling EMC virus infections.
PMID- 28405446
TI - Prevalence of virulence factors in enterotoxigenic Escherichia coli isolated from
pigs with post-weaning diarrhoea in Europe.
AB - BACKGROUND: Post-weaning diarrhoea (PWD), due to Escherichia coli, is an
important cause of economic losses to the pig industry primarily as a result of
mortality and worsened productive performance. In spite of its relevance, recent
data about the prevalence of virulence genes and pathotypes among E. coli
isolates recovered from cases of PWD in Europe are scarce. RESULTS: This study
investigates the prevalence of fimbrial and toxin genes of E. coli by PCR among
280 farms with PWD across Europe. A total of 873 samples collected within the
first 48 h after the onset of PWD (occurring 7-21 days post weaning) were
submitted to the laboratory for diagnostic purposes. Isolation and identification
of E. coli were performed following standard bacteriological methods and PCR
assays for the detection of genes encoding for fimbriae (F4, F5, F6, F18 and F41)
and toxins (LT, STa, STb and Stx2e). The prevalence of fimbriae and toxins among
E. coli isolates from cases of PWD was: F4 (45.1 %), F18 (33.9 %), F5 (0.6 %), F6
(0.6 %), F41 (0.3 %), STb (59.1 %), STa (38.1 %), LT (31.9 %) and Stx2e (9.7 %).
E. coli isolates carrying both fimbrial and toxin genes were detected in 52.5 %
of the cases (178 out of 339 isolates), with 94.9 % of them being classified as
enterotoxigenic E. coli (ETEC). The most common virotype detected was F4, STb,
LT. CONCLUSIONS: This study confirms that ETEC is frequently isolated in pig
farms with PWD across Europe, with F4- and F18-ETEC variants involved in 36.1 %
and 18.2 % of the outbreaks, respectively.
PMID- 28405447
TI - Impact of two mycotoxins deoxynivalenol and fumonisin on pig intestinal health.
AB - Mycotoxins are secondary metabolites of fungi that grow on a variety of
substrates. Due to their high consumption of cereals and their sensitivity, pigs
are highly impacted by the presence of mycotoxins. At the European level,
regulations and recommendations exist for several mycotoxins in pig feed. Among
these toxins, fumonisin B1 (FB1), and deoxynivalenol (DON) have a great impact on
the intestine and the immune system. Indeed, the intestine is the first barrier
to food contaminants and can be exposed to high concentrations of mycotoxins upon
ingestion of contaminated feed. FB1 and DON alter the intestinal barrier, impair
the immune response, reduce feed intake and weight gain. Their presence in feed
increases the translocation of bacteria; mycotoxins can also impair the immune
response and enhance the susceptibility to infectious diseases. In conclusion,
because of their effect on the intestine, FB1 and DON are a major threat to pig
health, welfare and performance.
PMID- 28405448
TI - Production results from piglets vaccinated in a field study in Spain with a Type
1 Porcine Respiratory and Reproductive virus modified live vaccine.
AB - BACKGROUND: PRRS is a viral disease of pigs and sows that is one of the most
costly to the pig industry worldwide. The disease can be controlled by focusing
on different aspects. One of them is the vaccination of piglets, which is more
controversial and difficult to manage than the vaccination of sows. However, pig
producers could consider a piglet vaccination strategy if it reduces the negative
clinical disease and improves zootechnical performance, decreases the probability
to be infected and/or reduces the spread of the virus once the vaccinated piglet
is infected. The efficacy of a novel PRRS modified live vaccine (Ingelvac
PRRSFLEX(r) EU) was studied in a blinded, side-by-side placebo controlled field
study of piglet vaccination including piglets weaned for three consecutive weeks
(week groups 1, 2 and 3). RESULTS: This study established that PRRS piglet
vaccination resulted in significantly better weight gain, seen as early as 4
weeks after vaccination, in naturally challenged pigs. Vaccine efficacy was
supported by statistically significant increases in Average Daily Weight Gain
(ADWG) among week group 3 vaccinated pigs from vaccination to the end of the
study and statistically significant increases in bodyweight and ADWG from
inclusion to 10 weeks of age in week group 2 vaccinated piglets. However, no
differences were noted in week group 1 presumably because more than 30 % of the
vaccinated pigs were viremic at the time of vaccination. Furthermore, the
proportion of pigs showing any abnormal clinical sign at least once at any of the
examination time points was lower in vaccinated pigs than in control pigs. Based
on the viremia results (qPCR), early onset of PRRS was detected in this herd.
Viremia occurred at the time of vaccination in week group 1 and shortly after
vaccination in week groups 2 and 3. Peak wild type PRRSV infection was assumed at
4 weeks post vaccination in all groups based on the number of PRRS positive pigs
in the control groups. CONCLUSION: This study establishes that vaccination of
piglets with Ingelvac PRRSFLEX(r) EU at 4 weeks of age improves weight gain and
reduces the appearance of clinical sings during the growing period, even when the
piglets are infected shortly after vaccination.
PMID- 28405449
TI - Comparison of the antimicrobial consumption in weaning pigs in Danish sow herds
with different vaccine purchase patterns during 2013.
AB - BACKGROUND: There is growing concern about development of antimicrobial
resistance due to use of antimicrobials (AMs) in livestock production.
Identifying efficient alternatives, including vaccination, is a priority. The
objective of this study was to compare the herd-level amount of AMs prescribed
for weaner pigs, between Danish sow herds using varying combinations of vaccines
against Porcine Circovirus Type 2 (PCV2), Mycoplasma hyopneumoniae (MYC) and
Lawsonia intracellularis (LAW). It was hypothesised that herds purchasing
vaccines, use these to prevent disease, and hence reduce their AM consumption,
compared to herds purchasing fewer or no vaccines against these pathogens. Data
summarised over year 2013 were obtained from the Danish Central Husbandry
Register and the Danish VetStat database, in which prescriptions of medication
are recorded. All one-site indoor pig herds with >50 sows and >200 weaners were
selected. AMs prescribed for weaners was measured in animal daily doses (ADD) and
divided according to three indication groups (gastro-intestinal, respiratory
indication or total use). The analysis was based on three multivariable linear
regression models of the herd-level ADD for each indication group. The eight
vaccination combinations (2x2x2) were included as one explanatory variable, and
herd size, measured as the number of weaner pen places was included in the models
as a potential confounder. RESULTS: Out of the 1513 herds in the study, 1415 had
AMs prescribed for gastro-intestinal disorders, and 836 for respiratory
disorders. PCV2 vaccines were purchased in 880 herds, MYC vaccines in 787 and LAW
vaccines in 115 herds. Herds purchasing PCV2 and MYC vaccines had significantly
more AMs prescribed than herds not purchasing vaccines or only purchasing LAW
vaccines. CONCLUSION: In the present study, using register data covering 1 year,
we found an association between use of vaccination and increased amount of AMs
prescribed for weaners. This does not exclude that the vaccines work, just that
we were unable to detect this. The findings might be explained by some herds
experiencing clinical problems associated with MYC or PCV2 despite use of
vaccination. In other herds, it might reflect that vaccines applied to weaners
are used for disease prevention in finishers rather than in the weaners.
Information about vaccination protocols and herd health status was not available
at the time of the study. Hence, further studies are required to investigate
causality of the associations between use of AMs, vaccination practices and other
confounding on-farm factors.
PMID- 28405450
TI - Vaccination of piglets at 2 and 3 weeks of age with Ingelvac PRRSFLEX(r) EU
provides protection against heterologous field challenge in the face of
homologous maternally derived antibodies.
AB - BACKGROUND: Due to difficulties in eradicating porcine reproductive and
respiratory syndrome (PRRS) linked to biosecurity challenges, transmission of the
virus and the lack of efficient DIVA vaccines, successful control of PRRS
requires a combination of strict management measures and vaccination of both sows
and piglets. The present study aimed to assess the efficacy of a recently
developed MLV vaccine (Ingelvac PRRSFLEX(r) EU) in piglets at 2 and 3-weeks of
age in the presence of homologous maternally derived antibodies as the dams were
vaccinated with the same vaccine strain (ReproCyc(r) PRRS EU). METHODS: The study
was carried out on a Hungarian farrow to finish farm naturally infected with
PRRSv. The study was designed as a blind, placebo controlled side by side trial.
ORF5 sequence similarity of the vaccine strain and the resident field strain was
87.8 %. PRRS specific real-time quantitative PCR was performed from serum samples
to measure both the viral load and the frequency of virus positive animals.
RESULTS: At the time of the natural infection observed in the control group at 10
12 weeks of age, the number of viraemic animals did not increase significantly in
the vaccinated group. To understand the infection dynamics, positive PCR samples
with low Ct values were sequenced (ORF5) and the data analysis indicated the
circulation of wild type virus in both groups, however wild type virus was only
found in non-vaccinated animals. CONCLUSIONS: Our data indicate that piglets
vaccinated at as early as 2 weeks of age with Ingelvac PRRSFLEX(r) EU were
protected both in terms of proportion of viraemic animals and viraemia levels. It
has to be highlighted that these results were achieved in piglets with high
levels of homologous maternally derived antibodies (MDA) at the time of
vaccination.
PMID- 28405451
TI - Implementing drinking water feed additive strategies in post-weaning piglets,
antibiotic reduction and performance impacts: case study.
AB - BACKGROUND: Piglets at weaning suffer many stressors such as sudden change of
feed, change in group composition and the end of lactogenic immunity. These
stressors may cause poor growth performance. There is a need for alternatives to
support piglets during the weaning period. Organic acids are known to have a
positive effect on performance through reducing the pH and their antimicrobial
action. CONTEXT & PURPOSE: The purpose was to study the effect of the inclusion
of a free and buffered organic acid blend in drinking water on performance of
weaned pigs. Four-hundred and twenty pigs in a conventional herd were allocated
after weaning to one of three treatments and monitored during 4 weeks: group (1)
Full medication, group (2) organic acid blend + full medication, group (3)
organic acid blend + reduced medication. Average daily gain, feed intake and
water consumption was recorded at group level. RESULTS: During the overall study
period live weight and average daily gain of the piglets was significantly higher
(P <0.001) for treatment (3) compared to (1) and (2) (Table 1). Live weight was
significantly higher for treatment (3) compared to (1) from week 2 of the study
(Fig. 1). No significant differences were found for average daily feed intake.
FCR for treatment (3) improved by 1.0 compared to treatment (1) in week 1 (P
<0.05), while in week 2 and 3 no significant differences were found (Table 2).
Overall, FCR was with 0.3 difference significantly lower (P = 0.001) for
treatment (3) than for (1) and (2) (Table 1). Pigs receiving organic acids in
drinking water had significantly (P <0.05) higher water consumption than group
(1) in weeks 3 and 4 (Table 2). CONCLUSION & POTENTIAL IMPLICATIONS: The use of a
blend of free and buffered organic acids together with a reduced medication
program improves growth performance during the first month after weaning compared
to a control with full medication and a combination between organic acids and
full medication. This implies that organic acids could be used as a valid
alternative for antibiotic reduction in post-weaning pigs. The treatment also
increased the drinking water intake.
PMID- 28405452
TI - Partial substitution, with their chelated complexes, of the inorganic zinc,
copper and manganese in sow diets reduced the laminitic lesions in the claws and
improved the morphometric characteristics of the hoof horn of sows from three
Greek herds.
AB - BACKGROUND: Hoof lesions in sows have been associated with lameness and poor hoof
horn quality. The mechanical strength and quality of hoof horn is determined by
the density and diameter of horn tubules, which were recently associated with the
severity of lesions on the hoof wall of sows. Histologic changes that have
previously been described in cases of bovine laminitis, have also been observed
in the dermis and epidermis of the sows' claws. Trace elements, particularly
zinc, copper and manganese, occupy important roles as enzyme catalysts in the
process of keratin synthesis which determines the quality and the integrity of
the hoof epidermis. Therefore, the objective of this study was to investigate the
effect of diet supplementation with chelated zinc, copper and manganese,
partially substituting their inorganic form, on sow claw health and hoof horn
quality assessed by macroscopic, histologic and morphometric examination.
RESULTS: Clinically, the total claw lesion score was significantly lower in claws
of sows which received the "organic" diet compared to those of sows on the
"inorganic" diet. Histologically, lamellar hyperplasia was the most frequently
recorded change in the epidermis of the sows' claws regardless of the diet's
mineral source. The claws of the sows which received the organic diet were more
likely to have none or less histologic changes than at least one or more,
respectively, compared to those of the sows on the "inorganic" diet.
Morphometrically, the density and vertical and horizontal diameters of the horn
tubules was significantly higher and smaller, respectively, in the hoof horn of
sows which received the "organic" compared to those which received the
"inorganic" source diet. CONCLUSIONS: Partial substitution of the inorganic zinc,
copper and manganese in sows' diet with their chelated complexes, provided a
comparative advantage against a conventional, inorganic mineral source diet, at
least under the conditions examined in the current study, in terms of
macroscopic, histologic and morphometric criteria, characterizing the health and
horn quality status of sows' hooves.
PMID- 28405454
TI - Emergence of a virulent porcine reproductive and respiratory syndrome virus
(PRRSV) 1 strain in Lower Austria.
AB - BACKGROUND: In spring 2015, an outbreak of porcine reproductive and respiratory
syndrome (PRRS) struck Lower Austria caused by a PRRS virus (PRRSV) strain
spreading rapidly among both previously PRRSV negative and vaccinated pig herds.
This case report describes the first well-documented emergence of the PRRSV
strain responsible for this outbreak. CASE PRESENTATION: A PRRSV seronegative
piglet-producing farm in Lower Austria encountered losses in foetuses and
suckling piglets of up to 90 %; clinical signs in sows and nursery piglets
included fever and reduced feed intake. Additionally, high percentages of repeat
breeders and losses of up to 40 % in nursery piglets occurred. An infection with
PRRSV was suggested by the detection of antibodies by enzyme linked immunosorbent
assay and confirmed by quantitative real time PCR. The underlying PRRSV strain,
termed AUT15-33, was isolated by passage on porcine alveolar macrophages,
partially sequenced (ORF2-7) and grouped as PRRSV-1, subtype 1. In phylogenetic
analysis of the genome region coding for the structural proteins, ORF2-7, AUT15
33 clustered with Belgian strains but identities were as low as 88 %. In
contrast, analysis of ORF7 sequences revealed a close relationship to Croatian
strains from 2012 with an identity of 94 - 95 %. CONCLUSIONS: In the year
following the outbreak, the same PRRSV strain was identified repeatedly in
different regions of Austria. It can be speculated that the new strain has novel
advantageous properties.
PMID- 28405453
TI - Genetic resistance - an alternative for controlling PRRS?
AB - PRRS is one of the most challenging diseases for world-wide pig production.
Attempts for a sustainable control of this scourge by vaccination have not yet
fully satisfied. With an increasing knowledge and methodology in disease
resistance, a new world-wide endeavour has been started to support the combat of
animal diseases, based on the existence of valuable gene variants with regard to
any host-pathogen interaction. Several groups have produced a wealth of evidence
for natural variability in resistance/susceptibility to PRRS in our commercial
breeding lines. However, up to now, exploiting existing variation has failed
because of the difficulty to detect the carriers of favourable and unfavourable
alleles, especially with regard to such complex polygenic traits like resistance
to PRRS. New hope comes from new genomic tools like next generation sequencing
which have become extremely fast and low priced. Thus, research is booming world
wide and the jigsaw puzzle is filling up - slowly but steadily. On the other
hand, knowledge from virological and biomedical basic research has opened the way
for an "intervening way", i.e. the modification of identified key genes that
occupy key positions in PRRS pathogenesis, like CD163. CD163 was identified as
the striking receptor in PRRSV entry and its knockout from the genome by gene
editing has led to the production of pigs that were completely resistant to PRRSV
- a milestone in modern pig breeding. However, at this early step, concerns
remain about the acceptance of societies for gene edited products and regulation
still awaits upgrading to the new technology. Further questions arise with regard
to upcoming patents from an ethical and legal point of view. Eventually, the
importance of CD163 for homeostasis, defence and immunity demands for more
insight before its complete or partial silencing can be answered. Whatever path
will be followed, even a partial abolishment of PRRSV replication will lead to a
significant improvement of the disastrous herd situation, with a significant
impact on welfare, performance, antimicrobial consumption and consumer
protection. Genetics will be part of a future solution.
PMID- 28405455
TI - Pig castration: will the EU manage to ban pig castration by 2018?
AB - BACKGROUND: In 2010, the 'European Declaration on alternatives to surgical
castration of pigs' was agreed. The Declaration stipulates that from January 1,
2012, surgical castration of pigs shall only be performed with prolonged
analgesia and/or anaesthesia and from 2018 surgical castration of pigs should be
phased out altogether. The Federation of Veterinarians of Europe together with
the European Commission carried out an online survey via SurveyMonkey(c) to
investigate the progress made in different European countries. This study
provides descriptive information on the practice of piglet castration across 24
European countries. It gives also an overview on published literature regarding
the practicability and effectiveness of the alternatives to surgical castration
without anaesthesia/analgesia. RESULTS: Forty usable survey responses from 24
countries were received. Besides Ireland, Portugal, Spain and United Kingdom, who
have of history in producing entire males, 18 countries surgically castrate 80%
or more of their male pig population. Overall, in 5% of the male pigs surgically
castrated across the 24 European countries surveyed, castration is performed with
anaesthesia and analgesia and 41% with analgesia (alone). Meloxicam, ketoprofen
and flunixin were the most frequently used drugs for analgesia. Procaine was the
most frequent local anaesthetic. The sedative azaperone was frequently mentioned
even though it does not have analgesic properties. Half of the countries surveyed
believed that the method of anaesthesia/analgesia applied is not practicable and
effective. However, countries that have experience in using both anaesthesia and
post-operative analgesics, such as Norway, Sweden, Switzerland and The
Netherlands, found this method practical and effective. The estimated average
percentage of immunocastrated pigs in the countries surveyed was 2.7% (median =
0.2%), where Belgium presented the highest estimated percentage of
immunocastrated pigs (18%). CONCLUSION: The deadlines of January 1, 2012, and of
2018 are far from being met. The opinions on the animal-welfare-conformity and
the practicability of the alternatives to surgical castration without
analgesia/anaesthesia and the alternatives to surgical castration are widely
dispersed. Although countries using analgesia/anaesthesia routinely found this
method practical and effective, only few countries seem to aim at meeting the
deadline to phase out surgical castration completely.
PMID- 28405456
TI - Vaccination against parasites - status quo and the way forward.
AB - Although vaccination against various pathogens is integral to health management
of swine, vaccines against parasites have not yet been commercialized for the use
in pigs. The incentive to develop and commercialize anti-parasitic vaccines in
swine are twofold; on the one hand parasitic diseases which are economically
important, such as ascarosis and neonatal coccidiosis, could be controlled in a
sustainable manner; on the other hand, the transmission of zoonotic parasites,
such as Toxoplasma gondii or Cysticercus cellulosae, could be effectively
interrupted. Although experimental research indicates that vaccination against a
number of porcine parasites is feasible, development and commercialization of
potential vaccines so far has been very slow, as our knowledge on the host
parasite interplay in porcine parasitic infections is still very limited. In the
light of growing concerns regarding consumer health and antiparasitic drug
resistance, however, it is timely to re-direct R&D efforts to the development of
biological control options.
PMID- 28405457
TI - Factors for improving reproductive performance of sows and herd productivity in
commercial breeding herds.
AB - We review critical factors associated with reproductive performance of female
breeding pigs, their lifetime performance and herd productivity in commercial
herds. The factors include both sow-level and herd-level factors. High risk sow
level groups for decreasing reproductive performance of female pigs are low or
high parity, increased outdoor temperature, decreased lactation feed intake,
single inseminations, increased lactation length, prolonged weaning-to-first
mating interval, low birth weight or low preweaning growth rate, a few pigs born
alive at parity 1, an increased number of stillborn piglets, foster-in or nurse
sow practices and low or high age at first-mating. Also, returned female pigs are
at risk having a recurrence of returning to estrus, and female pigs around
farrowing are more at risk of dying. Herd-level risk groups include female pigs
being fed in low efficiency breeding herds, late insemination timing, high within
herd variability in pig flow, limited numbers of farrowing spaces and fluctuating
age structure. To maximize the reproductive potential of female pigs, producers
are recommended to closely monitor females in these high-risk groups and improve
herd management. Additionally, herd management and performance measurements in
high-performing herds should be targeted.
PMID- 28405458
TI - The effect of double nursing, an alternative nursing strategy for the hyper
prolific sow herd, on herd performance.
AB - BACKGROUND: Hyper-prolific sows produce more piglets than they can suckle, as the
number of milk producing teats of the sow is lower (twelve to sixteen) than the
number of live born piglets per litter. Farmers and farm workers are struggling
to feed this surplus of piglets. To minimize suckling piglet mortality, litter
size at 24 hours after parturition should not exceed the number of functional
teats of the sow. Strategies to adequately nurse or feed the surplus of piglets
after 24 hours are limited and mostly restricted to either fostering piglets by
other sows, supplying milk replacers (formula) or early weaning and rearing on
formula. CASE PRESENTATION: In this case report we describe the design and
application of a so called 'double nursing' strategy, for which one sow
simultaneously nurses two litters from birth to weaning. Piglet mortality and
reproductive parameters of sows that have nursed two litters are compared, over a
three year period, with those that nursed one litter. CONCLUSION: In this herd,
the double nursing strategy appeared to be a successful strategy. Double nursing
sows experienced a lower piglet mortality, despite the double nursing strategy.
The negative effects on reproduction proved to be limited, there was a negative
effect on litter size in subsequent litters, but no significant effect on the
interval weaning to next conception. It has to be noted though that not all
characteristics on which double nursing selection takes place, could be taken
into account during statistical analyses.
PMID- 28405459
TI - Field efficacy of Porcilis(r) PCV M Hyo versus a licensed commercially available
vaccine and placebo in the prevention of PRDC in pigs on a French farm: a
randomized controlled trial.
AB - BACKGROUND: A controlled, randomised, and blinded trial performed on a
conventional French farrow-to-finish farm compared the efficacy of a one-shot
bivalent ready to use vaccine, Porcilis(r) PCV M. Hyo (group PCVM), to that of
two commercial vaccines (Ingelvac(r) Circoflex(r) + Ingelvac(r) Mhyo, group
ICIM), and to a placebo (group CTL), in preventing the health and economic
impacts of Porcine Respiratory Disease Complex (PRDC). MATERIAL & METHODS: In
this small-scale clinical study, all piglets in each group were administered the
vaccine/placebo at weaning age (27 days old). Piglets from either of the three
groups were bled at regular intervals from 3 weeks of age until slaughter, in
order to assess the infection by the main PRDC infectious agents: Mycoplasma
hyopneumoniae, PCV2 and PRRSV. Performance, lung checks and slaughter data were
collected and analysed. RESULTS: PCV2 viremia was significantly reduced in both
vaccinated groups as compared to the placebo group. Lung lesion score was
significantly lower in group PCVM, as compared to groups CTL and ICIM. Average
daily weight gain during the finishing period was not significantly different
between both vaccinated groups and was significantly higher than in the placebo
group (849 g/d in the latter). Carcass results provided a numerical advantage to
PCVM group, through improved part of production eligible for premium payment, and
superior farmer income; this was a trend and did not reach significance.
CONCLUSION: The one-shot bivalent vaccine Porcilis(r) PCV M Hyo proved to be
efficacious and convenient to use in a field context of active PCV2 and M.
hyopneumoniae infections.
PMID- 28405460
TI - Provision of straw by a foraging tower -effect on tail biting in weaners and
fattening pigs.
AB - BACKGROUND: Straw is one of the most effective rooting materials to reduce tail
biting in pigs. A so-called foraging-tower (FT) provides only small quantities of
straw compatible with liquid manure systems. The focus of the present study was
on the effect of providing straw by FT in order to prevent tail biting in tail
docked pigs. Four consecutive batches of 160 pigs, randomly divided into a straw
(SG) and a control group (CG) were followed up from weaning to slaughter.
RESULTS: Tail wounds (Score >= 2) were detected in 104 out of 12,032 single
observations (SG n = 48; CG n = 56) in 9 pens (SG n = 4/32; CG n = 5/32) mainly
focused on the fattening period of batch 2 due to a failure in the ventilation
system. No significant differences concerning the distribution of Score >= 2 in
pens of the SG and CG could be identified. Bite marks (Score 1) were documented
in 395 observations at animal level (SG n = 197, CG n = 198) in all batches. In
the nursery period, the air velocity significantly increased the chance that at
least one pig per pen and week showed a tail lesion score >=1 (p = 0.024). In the
fattening period ammonia concentration was positively associated with tail
lesions (p = 0.007). The investigation of blood samples revealed infections with
Mycoplasma hyopneumoniae in all batches and a circulation of Porcine Reproductive
and Respiratory Syndrome Virus (NA-vaccine strain) and Porcine Circovirus Type 2
in two batches each. The average daily straw consumption was 3.5 g/pig (standard
deviation (SD) = 1.1) during the rearing period and 31.9 g/pig (SD = 7.7) during
the fattening period. CONCLUSION: Due to the low prevalence of tail biting in all
batches the effect of the FT tower could not be evaluated conclusively. The
operation of the FT with an average daily straw consumption of 3.5 g/pig (SD =
1.1) during the rearing period and 31.9 g/pig (SD = 7.7) during the fattening
period did not affect the weight gain. Exploratory behaviour seems to cause bite
marks (score 1), which do not necessarily result in tail biting. The main
outbreak of tail biting was probably triggered by a failure of the ventilation
system, which resulted in a number of climatic and air quality changes including
higher ammonia concentrations and sudden temperature changes.
PMID- 28405461
TI - Feed additives decrease survival of delta coronavirus in nursery pig diets.
AB - BACKGROUND: Feed contaminated with feces from infected pigs is believed to be a
potential route of transmission of porcine delta coronavirus (PDCoV). The
objective of this study was to determine if the addition of commercial feed
additives (e.i., acids, salt and sugar) to swine feed can be an effective
strategy to inactive PDCoV. RESULTS: Six commercial feed acids (UltraAcid P,
Activate DA, KEMGEST, Acid Booster, Luprosil, and Amasil), salt, and sugar were
evaluated. The acids were added at the recommended concentrations to 5 g aliquots
of complete feed, which were also inoculated with 1 mL of PDCoV and incubated for
0, 7, 14, 21, 28, and 35 days. In another experiment, double the recommended
concentrations of these additives were also added to the feed samples and
incubated for 0, 1, 3, 7, and 10 days. All samples were stored at room
temperature (~25 degrees C) followed by removal of aliquots at 0, 7, 14, 21, 28,
and 35 days. Any surviving virus was eluted in a buffer solution and then
titrated in swine testicular cells. Feed samples without any additive were used
as controls. Both Weibull and log-linear kinetic models were used to analyze
virus survival curves. The presence of a tail in the virus inactivation curves
indicated deviations from the linear behavior and hence, the Weibull model was
chosen for characterizing the inactivation responses due to the better fit. At
recommended concentrations, delta values (days to decrease virus concentration by
1 log) ranged from 0.62-1.72 days, but there were no differences on virus
survival among feed samples with or without additives at the manufacturers
recommended concentrations. Doubling the concentration of the additives reduced
the delta value to <= 0.28 days (P < 0.05) for all the additives except for
Amasil (delta values of 0.86 vs. 4.95 days). Feed additives that contained
phosphoric acid, citric acid, or fumaric acid were the most effective in reducing
virus survival, although none of the additives completely inactivated the virus
by 10- days post-inoculation. CONCLUSIONS: Commercial feed additives (acidifiers
and salt) may be utilized as a strategy to decrease risk of PDCoV in feed,
specially, commercial feed acidifiers at double the recommended concentrations
reduced PDCoV survival in complete feed during storage at room temperature.
However, none of these additives completely inactivated the virus.
PMID- 28405462
TI - Effect of a GnRH analogue (peforelin) on the litter performance of gilts and
sows.
AB - BACKGROUND: Maintaining optimal reproductive and litter performance is essential
for meeting economic targets in commercial pig production. Treatment with
exogenous gonadotropins in sows after weaning or in gilts after altrenogest
treatment has been used to stimulate follicular development leading to more
piglets born and eventually higher birth weights. The effect of peforelin on
litter performance was investigated in 212 gilts, primi- and pluriparous sows in
three herds. Animals were randomly allocated to three treatments 24 h after
weaning: peforelin (P group), eCG (E group), and physiological saline solution (C
group). Numbers of total, liveborn and stillborn piglets and mortality rate
during lactation were recorded. Birth weights and coefficient of variation in
weights within litter were assessed. All parameters were compared among
treatments. RESULTS: Over all parities, no difference was found among treatments
in litter size nor mortality rate, but birth weights were significantly lower in
the E group. Stillbirth numbers in pluriparous sows were 2.2, 0.9 and 1.4 for P,
E and C groups, respectively (p = 0.04). Piglets in the P group had significantly
higher live born birth weights in gilts, compared to the E group (1.36, 1.26,
1.32 kg (p < 0.02) for P, E and C group, respectively). No significant
differences were found for the other investigated parameters. CONCLUSIONS:
Peforelin treatment showed no improvement of litter performance compared to no
treatment.
PMID- 28405463
TI - The use of oral fluids to monitor key pathogens in porcine respiratory disease
complex.
AB - BACKGROUND: The usefulness of oral fluid (OF) sampling for surveillance of
infections in pig populations is already accepted but its value as a tool to
support investigations of porcine respiratory disease complex (PRDC) has been
less well studied. This study set out to describe detection patterns of porcine
reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2
(PCV2), swine influenza virus type A (SIV) and Mycoplasma hyopneumoniae (M. hyo)
among farms showing differing severity of PRDC. The study included six wean-to
finish pig batches from farms with historical occurrence of respiratory disease.
OF samples were collected from six pens every two weeks from the 5th to the 21st
week of age and tested by real time PCR for presence of PRRSV, SIV and M. hyo and
by quantitative real time PCR for PCV2. Data was evaluated alongside clinical and
post-mortem observations, mortality rate, slaughter pathology, histopathology,
and immunohistochemistry testing data for PCV2 antigen where available. RESULTS:
PRRSV and M. hyo were detectable in OF but with inconsistency between pens at the
same sampling time and within pens over sequential sampling times. Detection of
SIV in clinical and subclinical cases showed good consistency between pens at the
same sampling time point with detection possible for periods of 2-4 weeks.
Quantitative testing of OF for PCV2 indicated different patterns and levels of
detection between farms unaffected or affected by porcine circovirus diseases
(PCVD). There was good correlation of PCR results for multiple samples collected
from the same pen but no associations were found between prevalence of positive
test results and pen location in the building or sex of pigs. CONCLUSIONS:
Detection patterns for PRRSV, SIV and M. hyo supported the effectiveness of OF
testing as an additional tool for diagnostic investigation of PRDC but emphasised
the importance of sampling from multiple pens and on multiple occasions.
Preliminary evidence supported the measurement of PCV2 load in pooled OF as a
tool for prediction of clinical or subclinical PCVD at farm level.
PMID- 28405464
TI - The use of vaccines to control pathogen spread in pig populations.
AB - Vaccine efficacy has often been studied from the viewpoint of individual direct
clinical protection. For several vaccines, a decrease in pathogen shedding in
vaccinated animals has also been documented, which suggests that transmission
between individuals has the potential to be reduced. In addition, vaccination
induces an immune response in the host potentially decreasing susceptibility to
infection in comparison with immunologically naive animals. As a collective
result of individual vaccinations, vaccine programmes generally have a wider
impact on pathogen diffusion at the population scale. Beyond the individual
protection conferred by mass vaccination campaigns, the indirect protection of
non-immune individuals in contact with vaccinated ones also contributes to
controlling pathogen spread at the population scale; a phenomenon known as herd
immunity. Pathogen spread within pig populations is strongly related to the
required vaccine coverage at the population level and to pathogen characteristics
in terms of diffusion ([Formula: see text]). Before setting up vaccination
programmes, it is therefore necessary to have quantitative knowledge on vaccine
efficacy as regards transmission reduction. These data can be obtained by
carrying out experimental studies or observational protocols in real conditions.
These quantitative data have mainly been estimated for major infectious diseases
which have now been eradicated. A great gap in knowledge has however been
identified for enzootic diseases which are daily impacting the swine sector as
well as for the source of variation responsible for a decrease in vaccine
efficacy as compared to assessments obtained in experimental conditions.
PMID- 28405465
TI - Effect of the needle-free "intra dermal application of liquids" vaccination on
the welfare of pregnant sows.
AB - BACKGROUND: In commercial pig production, sows are often vaccinated several times
per gestation period, resulting in reduced welfare. This preliminary experiment
investigated whether the needle-free IDAL vaccinator improves welfare through
reduction of stress markers, improvement of behavioural and health parameters
compared to traditional needle-syringe method. RESULTS: Two treatments (IDAL and
NEEDLE) in 6 replicate pens of gestating sows (15 sows per pen) were evaluated
using Porcilis(r) PRRS. The frequency of sows exhibiting an acute fear (or pain)
response at the time of injection was significantly lower in the IDAL sows for
the four indicators studied (high pitch vocalizations, IDAL = 15.4% vs. NEEDLE =
95.6%, chi2 = 56, P < 0.0001; retreat attempts, IDAL = 2.6% vs. NEEDLE = 56.5%,
chi2 = 28, P < 0.0001; turning back, IDAL = 5.1% vs. NEEDLE = 69.6%, chi2 = 36, P
< 0.0001; change in behaviour, IDAL = 18% vs. NEEDLE = 95.6%, chi2 = 53, P <
0.001). Sows in the NEEDLE vaccination group had a decreased (P = 0.03) activity
the day after vaccination compared to IDAL sows. No significant difference was
observed for the other active behaviours and resting postures. Fearful reaction
towards the assessor significantly (chi2 = 12, P = 0.001) increased in NEEDLE
sows compared to IDAL sows the day after vaccination. At 48 h post-vaccination,
IDAL sows tended to have lower blood C-reactive protein levels (IDAL = 21.3
MUg/mL vs. NEEDLE = 35.8 MUg/mL, P = 0.06) compared to NEEDLE sows. Blood
Haptoglobin levels did not differ significantly between treatments 48 h post
vaccination. Chromogranin A tended to show a lower increase after the IDAL
treatment, whereas salivary alpha-amylase and salivary cortisol did not differ
between treatments when measured 25 min post-vaccination. CONCLUSIONS: These
preliminary results support that needle-free intradermal vaccination is a
promising strategy to reduce fear and pain reaction of gestating sows during
vaccination.
PMID- 28405466
TI - Potentially effective therapy of heavy menstrual bleeding with an oestradiol
nomegestrol acetate oral contraceptive: a pilot study.
AB - BACKGROUND: Heavy menstrual bleeding (HMB) exceeding 80 mL per cycle leads to
considerable adverse impact on a woman's iron metabolism, incidence of iron
deficiency and anaemia, as well as her functioning in society. The objective of
the study is to determine the potential efficacy of a Monophasic oestradiol
17beta-nomegestrol acetate (E2/Nomac) combined oral contraceptive pill on
measured menstrual blood loss as a pilot study in 12 women with objectively
demonstrated HMB (>80 mL per cycle). The pilot study aimed to recruit 20 women.
METHOD: Consented women completed the HMB questionnaire. The blood was taken for
haemoglobin, transferrin, iron saturation, TIBC, serum iron and ferritin. Women
were given verbal and written detailed instructions for MBL collection for three
control cycles and four treatment cycles. RESULTS: Forty-three women were
enrolled, but 31 were ineligible and withdrawn (mainly for failure to meet
eligibility criteria). Twelve women entered the treatment phase and commenced the
E2/nomegestrol acetate (NOMAC) 24/4 combined pill treatment on the first day of
their fourth cycle. All women with complete MBL measurements had >50% reduction
in MBL on treatment (exact 95% confidence interval for proportion with MBL
reduction >50%: 69 to 100%). The mean percent reduction in MBL between
pretreatment and during treatment was 76.9%, and the median was 79% with a range
of 53.7 to 100%. CONCLUSIONS: This pilot study indicates that the E2/NOMAC COC
will provide a useful potential option for treating HMB in women with FIGO
classification AUB-E (primary endometrial causes) but requires a larger placebo
controlled study for confirmation.
PMID- 28405467
TI - Anti-apoptotic effect of dexamethasone in an ototoxicity model.
AB - BACKGROUND: Dexamethasone (DEX) is used for the treatment of various inner ear
diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell
damage is not known. Therefore, this study investigated the protective effect of
DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression
of apoptosis related genes. METHODS: The protective effects of DEX were measured
by phalloidin staining of explant cultures of organ of Corti from postnatal day 2
3 mice with GM-induced hair cell loss. Terminal deoxynucleotidyl transferase dUTP
nick end labeling staining was used to detect apoptosis and immunofluorescence
was done to analyze the effect of DEX on the expression of apoptosis related
genes. RESULTS: Cochlear explant cultures of postnatal day-4-old mice were
exposed to 0, 1, 5, 10, 30, 50, and 100 MUg/ml DEX and GM during culture. DEX
protected from GM-induced hair cell loss in the inner ear of postnatal day 4
mice. To understand the molecular mechanisms by which DEX pre-treatment decreased
hair cell loss, the testes of cochlear explant cultures of postnatal day 4 mice
were examined for changes in expression of cochlear apoptosis mediators. The pro
apoptotic protein Bax was significantly down-regulated and numbers of apoptotic
hair cells were decreased. CONCLUSIONS: DEX has a protective effect on GM-induced
hair cell loss in neonatal cochlea cultures and the protective mechanism may
involve inhibition of the mitochondrial apoptosis pathway. The combination with
scaffold technique can improve delivery of DEX into the inner ear to protect GM
induced ototoxicity.
PMID- 28405468
TI - cryptochrome genes form an oscillatory loop independent of the per/tim loop in
the circadian clockwork of the cricket Gryllus bimaculatus.
AB - BACKGROUND: Animals exhibit circadian rhythms with a period of approximately 24 h
in various physiological functions, including locomotor activity. This rhythm is
controlled by an endogenous oscillatory mechanism, or circadian clock, which
consists of cyclically expressed clock genes and their product proteins.
cryptochrome (cry) genes are thought to be involved in the clock mechanism, and
their functions have been examined extensively in holometabolous insects, but in
hemimetabolous insects their role is less well understood. RESULTS: In the
present study, the role of cry genes was investigated using RNAi technology in a
hemimetabolous insect, the cricket Gryllus bimaculatus. Using a molecular cloning
approach, we obtained cDNAs for two cry genes: Drosophila-type cry1 (Gb'cry1) and
mammalian-type cry2 (Gb'cry2). Gb'cry2 has six splicing variants, most of which
showed rhythmic mRNA expression. Gb'cry1RNAi treatment had only a limited effect
at the behavioral and molecular levels, while Gb'cry2RNAi had a significant
effect on behavioral rhythms and molecular oscillatory machinery, alone or in
combination with Gb'cry1RNAi. In Gb'cry1/Gb'cry2 double-RNAi crickets, most clock
genes showed arrhythmic expression, except for timeless, which retained clear
rhythmic expression. Molecular analysis revealed that some combination of Gb'cry1
and Gb'cry2 variants suppressed CLK/CYC transcriptional activity in cultured
cells. CONCLUSION: Based on these results, we propose a new model of the
cricket's circadian clock, including a molecular oscillatory loop for Gb'cry2,
which can operate independent of the Gb'per/Gb'tim loop.
PMID- 28405469
TI - What causes a small increase in radiographic progression in rheumatoid arthritis
patients tapering TNF inhibitors?
AB - OBJECTIVE: In a randomised controlled trial investigating tapering of TNF
inhibitors (TNFi) compared with usual care (UC) in rheumatoid arthritis patients,
minimal radiographic progression was more frequent in patients who attempted
tapering. Possible explanations include higher incidence of flaring, higher mean
disease activity or lower TNFi use. METHODS: 18 months data from the DRESS study
were used. Change in Sharp-van der Heijde (DeltaSvdH) score (linear regression)
and proportion of patients with >0.5 DeltaSvdH (logistic regression) were used as
outcomes. The cumulative incidence and number of short-lived and major flares per
patient, mean time-weighted disease activity (MTW-DAS28-CRP) and TNFi use were
used as independent variables. Regression models were performed stratified per
study group and corrected for possible confounders. RESULTS: 175 of 180 patients
had 18-month data available. The mean DeltaSvdH were 0.75 and 0.15 units with 37
of 116 (32%) and 9 of 59 (15%) patients exceeding 0.5 points in the tapering and
UC group, respectively (both p<0.05). MTW-DAS28-CRP, but not incidence or number
of short-lived or major flares, or TNFi use, was independently associated with
the mean progression score, but only in the tapering group. Additional analyses
on DAS28-CRP subcomponents showed that this was mainly caused by MTW swollen
joint count. No confounders were identified. CONCLUSIONS: Radiographic
progression was associated with higher MTW-DAS28-CRP (and especially swollen
joint count), but only in patients who tapered TNFi. This finding stresses the
importance of maintaining disease activity as low as possible in patients in whom
TNFi is tapered and to check for radiographic progression regularly. TRIAL
REGISTRATION NUMBER: NTR 3216; Post-results.
PMID- 28405470
TI - Is vascular endothelial growth factor a useful biomarker in giant cell arteritis?
AB - OBJECTIVES: To assess the performance of circulating vascular endothelial growth
factor (VEGF) levels as a tool for diagnosing giant cell arteritis (GCA) in a
cohort of patients referred for assessment of suspected GCA. METHODS: We selected
298 patients recruited to the multicentre study Temporal Artery Biopsy versus
Ultrasound in diagnosis of suspected GCA (TABUL). In a random subset of 26 biopsy
proven GCA cases and 26 controls, serum from weeks 0, 2 and 26 was analysed for
VEGF concentration using ELISA. VEGF concentration at week 0 was used to generate
a receiver-operating characteristic curve and thereby identify a cut-off for an
abnormal result which was used to analyse the full patient cohort. Sections of
paraffin-embedded temporal artery were stained by immunohistochemistry for VEGF.
RESULTS: The mean (95% CI) VEGF concentration at week 0 was 873 pg/mL (631 to
1110) in 26 patients versus 476 pg/mL (328 to 625) in 26 controls (p=0.017). This
difference was not observed at any other time point. The optimal cut-off of 713
pg/mL was applied to the whole patient cohort (n=298), yielding sensitivity of
32% and specificity of 85%. This was not improved by combination with any
clinical parameters. When patients with biopsy-proven GCA were compared with
controls, sensitivity was 58% and specificity remained 85%. Sections of biopsy
from biopsy-positive GCA showed intense staining in the adventitia which was not
seen in controls. CONCLUSIONS: Serum VEGF concentration predicts biopsy
positivity but is not useful for differentiating clinical cases of GCA from
controls. Further studies into VEGF as a prognostic marker and therapeutic target
are warranted. TRIAL REGISTRATION NUMBER: NCT00974883; Post-results.
PMID- 28405471
TI - MRI-based hip cartilage measures in osteoarthritic and non-osteoarthritic
individuals: a systematic review.
AB - Osteoarthritis is a common hip joint disease, involving loss of articular
cartilage. The prevalence and prognosis of hip osteoarthritis have been difficult
to determine, with various clinical and radiological methods used to derive
epidemiological estimates exhibiting significant heterogeneity. MRI-based methods
directly visualise hip joint cartilage, and offer potential to more reliably
define presence and severity of osteoarthritis, but have been underused. We
performed a systematic review of MRI-based estimates of hip articular cartilage
in the general population and in patients with established osteoarthritis, using
MEDLINE, EMBASE and SCOPUS current to June 2016, with search terms such as 'hip',
'femoral head', 'cartilage', 'volume', 'thickness', 'MRI', etc. Ultimately, 11
studies were found appropriate for inclusion, but they were heterogeneous in
osteoarthritis assessment methodology and composition. Overall, the studies
consistently demonstrate the reliability and potential clinical utility of MRI
based estimates. However, no longitudinal data or reference values for hip
cartilage thickness or volume have been published, limiting the ability of MRI to
define or risk-stratify hip osteoarthritis. MRI-based techniques are available to
quantify articular cartilage signal, volume, thickness and defects, which could
establish the sequence and rate of articular cartilage changes at the hip that
yield symptomatic osteoarthritis. However, prevalence and rates of progression of
hip osteoarthritis have not been established in any MRI studies in the general
population. Future investigations could fill this important knowledge gap using
robust MRI methods in population-based cross-sectional and longitudinal studies.
PMID- 28405472
TI - Course of patients with juvenile spondyloarthritis during 4 years of observation,
juvenile part of GESPIC.
AB - OBJECTIVE: To describe the course and the 4-year outcome of juvenile
spondyloarthritis (jSpA). METHODS: Patients with a diagnosis of jSpA and an age
at onset <=16 years were included in the German Spondyloarthritis Inception
cohort (GESPIC) and followed up prospectively for 4 years. RESULTS: 118 patients
(73% men, 66% HLA-B27 positive, mean age 13.5 years, mean symptom duration 2.2
years) were enrolled in 2 study centres: 52% of patients with jSpA were captured
by the enthesitis-related arthritis subgroup of the International League of
Associations for Rheumatology classification criteria. At inclusion, the majority
of patients had active peripheral arthritis (75.4%), followed by inflammatory
back pain (IBP) (19.5%) and enthesitis (16.1%). There was a significant
improvement in clinical manifestations and in patient-reported outcomes over
time. During the 4-year follow-up, 85% of the patients had at least 1 period of
remission on drug >=6 months, and 46% of the patients achieved remission >=12
months without medication, of whom 68% kept this status and 32% worsened. At the
end of 4 years of observation, 23% of the patients were in remission without
medication, but 57% still suffered from active disease. Patients with peripheral
arthritis had a likelihood of 29% for having peripheral arthritis after 4 years,
whereas the likelihood of IBP persistence was 53% for those with IBP at
enrolment. CONCLUSIONS: Although 1 quarter of patients with jSpA achieved
remission off medication after 4 years, the likelihood of having recurrent or
persistent disease into adulthood is substantial, particularly for jSpA with IBP.
TRIAL REGISTRATION NUMBER: NCT 01277419.
PMID- 28405473
TI - Patient-reported outcomes from a phase III study of baricitinib in patients with
conventional synthetic DMARD-refractory rheumatoid arthritis.
AB - OBJECTIVES: To evaluate the effect of baricitinib on patient-reported outcomes
(PROs) in patients with active rheumatoid arthritis (RA) and an inadequate
response or intolerance to conventional synthetic disease-modifying antirheumatic
drugs. METHODS: In this phase III study, patients were randomised 1:1:1 to
placebo (N=228), baricitinib 2 mg once daily (QD, N=229) or baricitinib 4 mg QD
(N=227). PROs included the Health Assessment Questionnaire-Disability Index (HAQ
DI), Patient's Global Assessment of Disease Activity (PtGA), patient's assessment
of pain, measures from patient electronic daily diaries (duration and severity of
morning joint stiffness (MJS), Worst Tiredness, Worst Joint Pain), Functional
Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), SF-36, EuroQol 5-D index
scores and visual analogue scales (VAS) and the Work Productivity and Activity
Impairment Questionnaire-RA. The primary time point for the study was week 12.
Treatment comparisons were assessed with logistic regression for categorical
measures and analysis of covariance for continuous variables. RESULTS:
Statistically significant improvements were observed for both baricitinib groups
versus placebo in HAQ-DI, PtGA, pain, daily diary measures, EuroQoL index scores
and SF-36 physical component score at week 12 and for those measures when
assessed at week 24. Baricitinib 2 mg and baricitinib 4 mg were statistically
significantly improved versus placebo for the EuroQoL VAS and FACIT-F,
respectively, at week 24. CONCLUSIONS: Baricitinib 2 or 4 mg provided significant
improvement versus placebo in PROs across different domains of RA, including
physical function, MJS, fatigue, pain and quality of life. TRIAL REGISTRATION
NUMBER: NCT01721057; Results.
PMID- 28405474
TI - Rheumatic immune-related adverse events of checkpoint therapy for cancer: case
series of a new nosological entity.
AB - Immunotherapy of cancer with checkpoint inhibitors has been associated with a
spectrum of autoimmune and systemic inflammatory reactions known as immune
related adverse events (irAEs). Rheumatic irAEs are infrequently reported and
extensively described. Here, we report our experience over an 18-month period
with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We
identified 13 patients without pre-existing autoimmune disease (AID) who
subsequently developed rheumatic irAEs, and two with established AID referred pre
emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome,
polymyalgia rheumatica-like symptoms and myositis. All cases required
glucocorticoids, and three required a biological agent. Rheumatic irAEs led to
temporary or permanent cessation of immunotherapy in all but five patients. One
patient with pre-existing AID experienced a flare after starting immunotherapy.
Our findings underscore that rheumatic irAEs are complex, at times require
additional immunosuppressive therapy, and may influence ongoing immunotherapy
regimens for the primary disease. Similar irAEs will be increasingly seen as
checkpoint inhibitors adopted as standard of care in the community.
PMID- 28405475
TI - Modified-release prednisone for polymyalgia rheumatica: a multicentre,
randomised, active-controlled, double-blind, parallel-group study.
AB - OBJECTIVE: To assess the efficacy and safety of modified-release (MR) versus
immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)-naive
patients with polymyalgia rheumatica (PMR). METHODS: Patients were randomised to
double-blind MR prednisone (taken at approximately 22:00) or IR prednisone (taken
in the morning), 15 mg/day for 4 weeks. The primary end point was complete
response rate (>=70% reduction in PMR visual analogue scale, duration of morning
stiffness and C reactive protein (CRP) (or CRP <2* upper limit of normal (ULN)))
at week 4. Non-inferiority was decided if the lower 95% confidence limit (MR vs
IR prednisone) was above -15%. 400 patients were planned but only 62 were
enrolled due to difficulties in recruiting GC-naive patients with PMR with CRP
>=2*ULN. RESULTS: The percentage of complete responders at week 4 was numerically
greater for MR prednisone (53.8%) than for IR prednisone (40.9%). Non-inferiority
of MR versus IR prednisone was not proven in the primary analysis on the per
protocol population (N=48; treatment difference: 12.22%; 95% CI -15.82% to
40.25%). However, sensitivity analysis on the full analysis population showed an
evident trend favouring MR prednisone (N=62; treatment difference: 15.56%; 95% CI
-9.16% to 40.28%). Adverse events were generally mild and transient with no
unexpected safety observations. CONCLUSIONS: The study showed a clear trend for
favourable short-term efficacy of MR prednisone versus IR prednisone in early
treatment of PMR. Further studies are warranted. TRIAL REGISTRATION NUMBER:
EudraCT number 2011-002353-57; Results.
PMID- 28405476
TI - Bilateral retinitis following typhoid fever.
AB - BACKGROUND: Post typhoid fever immune related reactions affecting the eye is a
rare finding which can have various presentations in which typhoid retinopathy is
not a well recognized sequelae. CASE PRESENTATION: Here we present a case of 59
year old male who presented with right eye sudden painless loss of vision 4 weeks
after typhoid fever which was diagnosed and treated successfully. His BCVA was
2/60 in right eye and 6/6 in left eye. Fundus examination showed retinitis along
with macular serous detachment in right eye and retinitis in left eye.
Significant improvement in BCVA in right eye was observed after treatment with
oral steroid with resolving retinitis lesions. Diagnosis of post typhoid immune
mediated retinitis was made with good resolution following treatment.
CONCLUSIONS: Immune mediated retinitis is a rare sequelae to typhoid infection
which can be successfully treated with systemic steroids with good resolution of
the lesions.
PMID- 28405477
TI - Influence of adaptive statistical iterative reconstruction algorithm on image
quality in coronary computed tomography angiography.
AB - BACKGROUND: Coronary computed tomography angiography (CCTA) requires high spatial
and temporal resolution, increased low contrast resolution for the assessment of
coronary artery stenosis, plaque detection, and/or non-coronary pathology.
Therefore, new reconstruction algorithms, particularly iterative reconstruction
(IR) techniques, have been developed in an attempt to improve image quality with
no cost in radiation exposure. PURPOSE: To evaluate whether adaptive statistical
iterative reconstruction (ASIR) enhances perceived image quality in CCTA compared
to filtered back projection (FBP). MATERIAL AND METHODS: Thirty patients
underwent CCTA due to suspected coronary artery disease. Images were
reconstructed using FBP, 30% ASIR, and 60% ASIR. Ninety image sets were evaluated
by five observers using the subjective visual grading analysis (VGA) and assessed
by proportional odds modeling. Objective quality assessment (contrast, noise, and
the contrast-to-noise ratio [CNR]) was analyzed with linear mixed effects
modeling on log-transformed data. The need for ethical approval was waived by the
local ethics committee as the study only involved anonymously collected clinical
data. RESULTS: VGA showed significant improvements in sharpness by comparing FBP
with ASIR, resulting in odds ratios of 1.54 for 30% ASIR and 1.89 for 60% ASIR (P
= 0.004). The objective measures showed significant differences between FBP and
60% ASIR (P < 0.0001) for noise, with an estimated ratio of 0.82, and for CNR,
with an estimated ratio of 1.26. CONCLUSION: ASIR improved the subjective image
quality of parameter sharpness and, objectively, reduced noise and increased CNR.
PMID- 28405478
TI - Comparison of Outcomes in Patients Who Underwent Deep Anterior Lamellar
Keratoplasty and Those Converted to Penetrating Keratoplasty.
AB - OBJECTIVES: To compare clinical outcomes of cases who underwent deep anterior
lamellar keratoplasty (DALK) and cases who were converted to penetrating
keratoplasty (PKP) from DALK surgery. MATERIALS AND METHODS: The records of 54
patients for whom DALK surgery was planned and were operated for different
diagnoses between March 2013 and June 2015 were retrospectively analyzed.
Patients were divided into two groups: group 1 (PKP group) consisted of 23 cases
who were converted to PKP due to Descemet's membrane perforation at any stage of
surgery; group 2 (DALK group) consisted of 31 patients whose surgery could be
completed as DALK. Preoperative and postoperative follow-up results were
evaluated in each group. RESULTS: Corrected distance visual acuity (CDVA)
increased in the postoperative period according to baseline in both groups.
However, there was no statistically significant difference in the rates of CDVA
increase between the groups (p=0.142). The mean astigmatism measured by corneal
topography at final examination was 5.8+/-2.3 diopters in group 1 and 5.4+/-1.8
diopters in group 2. The difference between groups was not statistically
significant (p=0.430). The groups were not statistically different regarding
postoperative pachymetry (p=0.453). The grafts in all 54 patients (100%) were
clear at final postoperative examination. There were no statistically significant
differences between the groups in terms of postoperative complications.
CONCLUSION: Similar clinical outcomes were obtained in our study for patients who
underwent DALK and those whose procedure was converted from DALK to PKP.
PMID- 28405479
TI - Comparison of Biofilm Formation Capacities of Two Clinical Isolates of
Staphylococcus Epidermidis with and without icaA and icaD Genes on Intraocular
Lenses.
AB - OBJECTIVES: To compare biofilm formations of two Staphylococcus epidermidis (S.
epidermidis) isolates with known biofilm formation capacities on four different
intraocular lenses (IOL) that have not been studied before. MATERIALS AND
METHODS: Two isolates obtained from ocular surfaces and identified in previous
studies and stored at -86 degrees C in 15% glycerol in the microbiology
laboratory of the Anadolu University Department of Biology were purified and used
in the study. The isolates were S. epidermidis KA 15.8 (ICA+), a known biofilm
producer isolate positive for icaA, icaD and bap genes, and S. epidermidis KA
14.5 (ICA-), known as a non-biofilm producer isolate negative for icaA, icaD and
bap genes. The biofilm formation capacities of the 2 isolates on 4 different IOLs
were compared. Two of the IOLs were acrylic (UD613 [IOL A], Turkey; SA60AT [IOL
B], USA), and the other two were polymethyl methacrylate (PMMA) (B60130C [IOL C],
India; B55125C [IOL D], India). Bacterial enumeration and optical density
measurements were done from biofilms that formed on the IOLs. Biofilms were
imaged using scanning electron microscopy. RESULTS: Mean bacterial counts on the
IOLs were 7.1+/-0.4 log10 CFU/mL with the ICA+ isolate, and 6.7+/-0.8 log10
CFU/mL with the ICA- isolate; there were no statistically significant
differences. Biofilm formation was lower with acrylic lenses than PMMA lenses
with both isolates (p=0.009 and p=0.013). The highest biofilm production was
obtained on IOL C (PMMA) (p<0.001) and the lowest was obtained on IOL A
(hydrophilic acrylic) (p<0.001). CONCLUSION: Bacterial counts after biofilm
formation were lower on acrylic lenses, especially hydrophilic acrylic with
hydrophobic properties. Further animal and in vivo studies are required to
support the findings of this study.
PMID- 28405480
TI - Contrast Sensitivity in Microtropic and Anisometropic Eyes of Successfully
Treated Amblyopes.
AB - OBJECTIVES: To assess and compare contrast sensitivity function in the previously
amblyopic and non-amblyopic "normal" eyes of patients with microtropia and
anisometropia who achieved 20/20 visual acuity after occlusion therapy. MATERIALS
AND METHODS: Contrast sensitivity was tested monocularly on both eyes of 34
successfully treated microtropic and 15 anisometropic subjects (visual acuity
20/20 in both eyes). Contrast sensitivity function was evaluated by CSV-1000E and
age-matched nomograms were used (spatial frequencies of 3, 6, 12, and 18 cycles
per degree [cpd]) for comparison. RESULTS: The mean age of subjects was 11.2+/
1.3 years in the microtropic group, 9.8+/-1.7 years in the anisometropic group (7
12 years); the mean follow-up time was 16.4+/-3.2 months (12 to 92) in the
microtropic group and 27.7+/-1.8 months (12-84) in the anisometropic group.
Statistical comparison of the microtropic amblyopic eyes versus non-microtropic
eyes showed significant differences at spatial frequencies of 3, 12 and 18 cpd (3
cpd, t=2.8, p=0.007; 6 cpd, t=1.1 p=0.261; 12 cpd, t=2.2, p=0.033; 18 cpd, t=2.2,
p=0.030). When anisometropic eyes were compared with non-anisometropic eyes,
there was a significant difference only at 12 cpd (t=2.1 p=0.049). The comparison
of non-amblyopic eyes versus age-matched nomograms revealed no differences at any
of the spatial frequencies (p>0.05 for all). CONCLUSION: Contrast sensitivity was
decreased in patients with amblyopia, especially in the microtropic group. The
assessment of contrast sensitivity function may serve as a new parameter for
termination of occlusion therapy.
PMID- 28405481
TI - Factors Affecting Contrast Sensitivity in Healthy Individuals: A Pilot Study.
AB - OBJECTIVES: To determine the demographic and ocular features affecting contrast
sensitivity levels in healthy individuals. MATERIALS AND METHODS: Seventy-four
eyes of 37 subjects (7-65 years old) with refractive errors less than 1.0
diopter, no history of ocular surgery, and 20/20 visual acuity were included in
the study. The participants were divided by age into three groups: group 1, 7-19
years, n=11; group 2, 20-49 years, n=15; and group 3, 50-65 years, n=11. All
subjects underwent anterior and posterior segment evaluation, intraocular
pressure measurements, refraction measurements, and clinical evaluation for
strabismus. Contrast static test was performed using Metrovision MonPack 3 vision
monitor system after measuring pupil diameter. Photopic and mesopic measurements
were taken sequentially from right eyes, left eyes, and both eyes together.
RESULTS: Contrast sensitivity at intermediate and high spatial frequencies was
lower with increasing age. Binocular measurements were better than monocular, and
mesopic measurements were better than photopic measurements at all spatial
frequencies. Contrast sensitivity at higher spatial frequency was lower with
hyperopic refraction values. CONCLUSION: Increasing age, small pupil diameter,
hyperopia, and photopic conditions were associated with lower contrast
sensitivity in healthy individuals. Binocular contrast sensitivity measurements
were better than monocular contrast sensitivity measurements in all conditions
and spatial frequencies.
PMID- 28405482
TI - The Relationship between Serum Carbonic Anhydrase I-II Autoantibody Levels and
Diabetic Retinopathy in Type 1 Diabetes Patients.
AB - OBJECTIVES: To investigate the relationship between serum carbonic anhydrase I-II
(CA-I and II) autoantibody levels and diabetic retinopathy (DRP) in cases with
type 1 diabetes. MATERIALS AND METHODS: A total of 37 type-1 diabetic patients,
17 with DRP (group 1) and 20 without (group 2), and 38 healthy control subjects
(group 3) were included. CA-I and CA-II autoantibody levels were measured in
serum samples obtained from each of the three groups and compared statistically.
Additionally, the correlation between CA-I and CA-II autoantibody levels and the
presence of diabetic macular edema was examined. RESULTS: Mean measured CA-I
autoantibody levels were 0.145+/-0.072, 0.117+/-0.047, and 0.138+/-0.061 ABSU in
group 1, group 2, and group 3, respectively (p=0.327). The average CA-II
autoantibody levels achieved in the same groups were 0.253+/-0.174, 0.155+/
0.137, and 0.131+/-0.085 ABSU, respectively (p=0.005). No significant difference
was obtained between the subgroups of group 1, with macular edema (n=8) and
without (n=9), in terms of both CA-I and CA-II autoantibody levels (p=0.501,
p=0.178, respectively). CONCLUSION: A significant correlation was observed
between the development of DRP and serum CA-II autoantibody levels in type 1
diabetic cases. However, there was no correlation between the autoantibody levels
and the presence of diabetic macular edema in cases with DRP.
PMID- 28405483
TI - Treatment Results in Serpiginous Choroiditis and Multifocal Serpiginoid
Choroiditis Associated with Latent Tuberculosis.
AB - OBJECTIVES: To compare the results of systemic antitubercular therapy (ATT) and
immunomodulatory therapy (IMT) in patients with serpiginous choroiditis (SC) or
multifocal serpiginoid choroiditis (MSC). MATERIALS AND METHODS: The clinical
records of 28 patients with SC and MSC were reviewed. Patients were divided into
2 groups according to the treatment applied. Group 1 included 12 patients with
MSC and 5 with SC treated with ATT and corticosteroid (CS); group 2 included 9
patients with MSC and 2 with SC treated with conventional IMT, interferon alpha
2a, and/or CS monotherapy. RESULTS: In group 1, clinical remission was achieved
in 12/12 MSC and 3/5 SC (total 15/17) patients with administration of ATT for 1
year. Two patients (1 SC, 1 MSC) had reactivation 2 and 7 months after cessation
of ATT. Two patients with recurrence after completion of ATT and 2 patients
resistant to ATT received IMT +/- CS therapy. In group 2, clinical remission was
achieved in 7/9 MSC and 2/2 SC (total 9/11) patients after 1 year of treatment.
Recurrent inflammation was observed in 2 MSC patients 2 and 112 months after
initiation of therapy, but responded well to local/systemic CS or IMT
modification, and clinical remission was achieved in 7.8+/-4.3 months. Cumulative
dose of CS was higher in group 2 (p=0.057). Nine of 12 MSC patients treated with
ATT and 4/9 MSC patients treated with IMT achieved remission (p=0.203). One of 5
SC patients treated with ATT and 2/2 SC patients treated with IMT achieved
remission (p=0.142). CONCLUSION: Although a statistically significant result
could not be achieved in this small case series, our results suggest that ATT may
be an appropriate first choice in the treatment of MSC associated with latent
tuberculosis, and may be administered in patients with SC who are unresponsive to
IMT.
PMID- 28405485
TI - Spontaneous Late Intraocular Lens and Capsule Tension Ring Dislocation.
AB - In this report, three cases with pseudoexfoliation (PEX) and advanced age with
spontaneous intraocular lens (IOL) and capsule tension ring (CTR) dislocation
were presented. All of our cases experienced progressive vision loss without an
episode of strenuous physical activity, trauma, or any other ocular disease.
Spontaneous dislocation was observed 2.5 to 8 years after uneventful
phacosurgery. Each patient underwent complete IOL and CTR removal combined with
anterior chamber IOL implantation. No complications were noticed during follow
up. As a result, capsule tension ring does not prevent late IOL dislocation after
uncomplicated phacosurgery in the presence of PEX. Therefore, close follow-up is
essential for patients with PEX.
PMID- 28405484
TI - Thyroid-associated Ophthalmopathy.
AB - Thyroid-associated ophthalmopathy is the most frequent extrathyroidal involvement
of Graves' disease but it sometimes occurs in euthyroid or hypothyroid patients.
Thyroid-associated ophthalmopathy is an autoimmune disorder, but its pathogenesis
is not completely understood. Autoimmunity against putative antigens shared by
the thyroid and the orbit plays a role in the pathogenesis of disease. There is
an increased volume of extraocular muscles, orbital connective and adipose
tissues. Clinical findings of thyroid-associated ophthalmopathy are soft tissue
involvement, eyelid retraction, proptosis, compressive optic neuropathy, and
restrictive myopathy. To assess the activity of the ophthalmopathy and response
to treatment, clinical activity score, which includes manifestations reflecting
inflammatory changes, can be used. Supportive approaches can control symptoms and
signs in mild cases. In severe active disease, systemic steroid and/or orbital
radiotherapy are the main treatments. In inactive disease with proptosis, orbital
decompression can be preferred. Miscellaneous treatments such as
immunosuppressive drugs, somatostatin analogs, plasmapheresis, intravenous
immunoglobulins and anticytokine therapies have been used in patients who are
resistant to conventional treatments. Rehabilitative surgeries are often needed
after treatment.
PMID- 28405486
TI - Rare Clinical Sign of Hodgkin's Lymphoma: Ocular Involvement.
AB - Bilateral non-granulomatous anterior uveitis with left vitritis and macular edema
were detected in a 19-year-old woman presenting with blurred vision in her left
eye. Light microscopic study of the pathologic mediastinal lymph node that was
detected via contrast computed tomography imaging during etiologic study revealed
nodular sclerosing and mixed cellularity Hodgkin's lymphoma (HL). Ocular findings
completely resolved with adriablastin, bleomycin, vinblastine, dacarbazine
chemotherapy treatment. Herein, it is emphasized that HL should be remembered as
one of the differential diagnoses in patients with ocular inflammatory
pathologies such as uveitis and vasculitis. The ocular findings of HL are
discussed.
PMID- 28405487
TI - Giant Hidrocystoma of the Orbit Presenting with Inversion and Ptosis of the Upper
Eyelid.
AB - A case of giant hidrocystoma of the orbit in a 57-year-old female causing pain,
epiphora and ptosis is reported. The cystic mass was totally excised as a whole.
Histopathologic examination revealed eccrine hidrocystoma of the orbit.
Hidrocystoma must be considered in the differential diagnosis of patients
presenting with periocular masses causing pain and ptosis.
PMID- 28405488
TI - Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal
Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome.
AB - Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is
characterized by small, round, discrete, macular or mid peripheral atrophic
(punched out) chorioretinal lesions (histo spots), peripapillary scarring,
choroidal neovascularization (CNV), and the absence of anterior uveitis and
vitritis. Diagnosis of this disorder is based upon characteristic clinical
findings and a positive histoplasmin skin test or residence in an endemic region
for Histoplasma capsulatum. There is no active systemic disease during diagnosis
of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known
complication which leads to loss of visual acuity or visual disturbance. Without
therapy, the visual prognosis in these patients is unfavorable. Submacular
surgery, radiation, steroids, photodynamic therapy, and most recently anti
vascular endothelial growth factor therapy are current therapeutic options for
this condition. We report a case with persistent CNV secondary to POHS in a
middle-aged woman with moderate myopia and the clinical course of treatment with
multiple intravitreal ranibizumab (Lucentis(r), Novartis) injections.
PMID- 28405490
TI - Intravitreal Bevacizumab in Vitreous Hemorrhage and Diabetes Mellitus.
PMID- 28405489
TI - Three-dimensional Optical Coherence Tomography Imaging and Treatment of
Glaucomatous Optic Nerve Head Defects Associated with Schisis-like Maculopathy.
AB - We present the three-dimensional (3D) spectral-domain optical coherence
tomography (SD-OCT) findings of schisis-like maculopathy associated with
structural changes of the optic nerve (ON) head as well as the treatment outcomes
of a case of advanced glaucoma. In addition to ophthalmological examination, B
scan and 3D-SD-OCT images of the ON head, peripapillary retina, and the macula
were obtained. The B-scan images only detected typical retinoschisis findings.
However, the 3D-SD-OCT images of the ON head revealed defects of various sizes,
shapes, and depths at the outer wall of the prelaminar and laminar regions of the
ON canal. The 3D images were able to establish that these defects were both
adjacent to and interconnected with the retinal layers. The patient successfully
received 3D-SD-OCT-guided thermal laser treatment that is used in congenital
optic disc pits complicated with macular schisis. In brief, 3D-SD-OCT is very
useful for demonstrating the ON head defects that can lead to schisis-like
maculopathy in cases of advanced glaucoma.
PMID- 28405491
TI - Transient Behavior of Ni@NiO x Functionalized SrTiO3 in Overall Water Splitting.
AB - Transients in the composition of Ni@NiO x core-shell co-catalysts deposited on
SrTiO3 are discussed on the basis of state-of-the-art continuous analysis of
photocatalytic water splitting, and post-XPS and TEM analyses. The formation of
excessive hydrogen (H2:O2 ? 2) in the initial stages of illumination demonstrates
oxidation of Ni(OH)2 to NiOOH (nickel oxyhydroxide), with the latter catalyzing
water oxidation. A disproportionation reaction of Ni and NiOOH, yielding Ni(OH)2
with residual embedded Ni, occurs when illumination is discontinued, which
explains repetitive transients in (excess) hydrogen and oxygen formation when
illumination is reinitiated.
PMID- 28405492
TI - A Rare Complication of Central Venous Catheter Extravasation in a Preterm
Neonate: Hemidiaphragmatic Paralysis.
AB - We report a case of a preterm neonate born at 26 weeks' of gestation diagnosed
with unilateral diaphragmatic paralysis. This paralysis was a consequence of a
phrenic nerve injury due to extravasation of hyperosmolar parenteral nutrition
fluid in the upper thorax. Chest X-rays and ultrasonography confirmed the
diagnosis. The neonate was treated with prolonged respiratory support and did not
require surgical treatment. This report describes a case of hemidiaphragmatic
paralysis as a complication of central venous catheter insertion. In neonates,
spontaneous recovery of diaphragmatic paralysis is possible. This study concludes
that recovery of extravasation injury-induced phrenic nerve palsy in the context
of conservative management is possible.
PMID- 28405493
TI - HLA class I-restricted MYD88 L265P-derived peptides as specific targets for
lymphoma immunotherapy.
AB - Genome sequencing has uncovered an array of recurring somatic mutations in
different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding
regions, such mutations may yield mutation-derived peptides that may be presented
by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic
and oncogenic driver mutation of the Toll-like receptor adaptor protein MYD88,
Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients.
We therefore screened the potential of MYD88L265P-derived peptides to elicit
cytotoxic T cell responses as tumor-specific neoantigens. Based on in silico
predictions, we identified potential MYD88L265P-containing HLA ligands for
several HLA class I restrictions. A set of HLA class I MYD88L265P-derived ligands
elicited specific cytotoxic T cell responses for HLA-B*07 and -B*15. These data
highlight the potential of MYD88L265P mutation-specific peptide-based
immunotherapy as a novel personalized treatment approach for patients with
MYD88L265P+ NHLs that may complement pharmacological approaches targeting
oncogenic MyD88 L265P signaling.
PMID- 28405494
TI - Overcoming resistance to HER2-targeted therapy with a novel HER2/CD3 bispecific
antibody.
AB - T-cell-based therapies have emerged as one of the most clinically effective ways
to target solid and non-solid tumors. HER2 is responsible for the oncogenesis and
treatment resistance of several human solid tumors. As a member of the HER family
of tyrosine kinase receptors, its over-activity confers unfavorable clinical
outcome. Targeted therapies directed at this receptor have achieved responses,
although development of resistance is common. We explored a novel HER2/CD3
bispecific antibody (HER2-BsAb) platform that while preserving the anti
proliferative effects of trastuzumab, it recruits and activates non-specific
circulating T-cells, promoting T cell tumor infiltration and ablating HER2(+)
tumors, even when these are resistant to standard HER2-targeted therapies. Its in
vitro tumor cytotoxicity, when expressed as EC50, correlated with the surface
HER2 expression in a large panel of human tumor cell lines, irrespective of
lineage or tumor type. HER2-BsAb-mediated cytotoxicity was relatively insensitive
to PD-1/PD-L1 immune checkpoint inhibition. In four separate humanized mouse
models of human breast cancer and ovarian cancer cell line xenografts, as well as
human breast cancer and gastric cancer patient-derived xenografts (PDXs), HER2
BsAb was highly effective in promoting T cell infiltration and suppressing tumor
growth when used in the presence of human peripheral blood mononuclear cells
(PBMC) or activated T cells (ATC). The in vivo and in vitro antitumor properties
of this BsAb support its further clinical development as a cancer
immunotherapeutic.
PMID- 28405495
TI - Biological and clinical significance of tryptophan-catabolizing enzymes in
cutaneous T-cell lymphomas.
AB - Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor
microenvironment (TME) and is recognized as a potential therapeutic target. We
studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase
(TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and
evaluated the kynurenine (KYN) pathway in the local TME and in patient sera.
Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n
= 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large
cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma
(SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were
analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative
PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three CTCL
cell lines also were studied. Expression of both IDO1 and TDO was upregulated in
CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded
that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding
Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among
CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP,
IDO1 was expressed by malignant cells and by CD33+ myeloid-derived suppressor
cells, whereas in SPTCL CD163+ tumor-associated macrophages also expressed IDO1.
Significantly elevated serum KYN/Trp ratios were found in patients with advanced
stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN
concentration in cell culture. These results show the importance of IDO1/TDO
induced immunosuppression in CTCL and emphasize its role as a new therapeutic
target.
PMID- 28405496
TI - IL-12, IL-15, and IL-18 pre-activated NK cells target resistant T cell acute
lymphoblastic leukemia and delay leukemia development in vivo.
AB - NK cells have shown promise in therapy of hematological cancers, in particular
against acute myeloid leukemia. In contrast, the more NK cell-resistant acute
lymphoblastic leukemia (ALL) is difficult to treat with NK-cell-based therapies,
and we hypothesized that pre-activation of NK cells could overcome this
resistance. We show in pediatric and adult patients with T-cell ALL (T-ALL)
perturbed NK cell effector functions at diagnosis. Using an in vivo rat model for
T-ALL, Roser leukemia (RL), suppressed NK cell effector functions were observed.
NK cells from T-ALL patients had reduced expression of the activating receptors
NKp46 and DNAM-1, but not NKG2D. In contrast to T-ALL patients, NKG2D but not
NKp46 was downregulated on NK cells during rat RL. Decreased frequencies of
terminally differentiated NKG2A+CD57-CD56dim NK cells in human T-ALL was
paralleled in the rat by reduced frequencies of bone marrow NK cells expressing
the maturation marker CD11b, possibly indicating impairment of differentiation
during leukemia. RL was highly resistant to autologous NK cells, but this
resistance was overcome upon pre-activation of NK cells with IL-12, IL-15, and IL
18, with concomitant upregulation of activation markers and activating receptors.
Importantly, adoptive transfers of IL-12, IL-15, and IL-18 pre-activated NK cells
significantly slowed progression of RL in vivo. The data thus shows that T-ALL
blasts normally resistant to NK cells may be targeted by cytokine pre-activated
autologous NK cells, and this approach could have potential implications for
immunotherapeutic protocols using NK cells to more efficiently target leukemia.
PMID- 28405497
TI - Results of a phase I-II study of adjuvant concurrent carboplatin and accelerated
radiotherapy for triple negative breast cancer.
AB - Purpose: To determine feasibility and explore the clinical efficacy of concurrent
radiotherapy and carboplatin as adjuvant treatment of triple negative breast
cancer (TNBC). Patients and Methods: Women with Stage I-II TNBC were treated
after surgery in a phase I-II prospective trial [NCT01289353]. Weekly carboplatin
(AUC = 2.0) was delivered for 6 weeks. Concurrent radiotherapy was delivered in
the prone position during weeks 2-4, for a total dose of 40.5 Gy in 15 fractions
to the breast, and 46.5 Gy in 17 fractions to the tumor bed. Adverse events (AE)
were assessed weekly during treatment, once at 45-60 d, and every 6 mo
thereafter, using the Common Terminology Criteria for AE (CTCAE) v3.0. Results: A
total of 39 patients accrued and 36 received treatment. Eight patients (22%,
exact 95% CI: 10%, 39%) developed grade 2 or greater acute radiation dermatitis.
Overall, grade 2 AE were seen in nine and grade 3 in two patients. Twenty-three
patients (64%) received additional adjuvant chemotherapy. With a median follow-up
of 48 mo, 34/36 (94%) are alive and disease free. One patient died of pulmonary
failure with possible but unproven breast cancer recurrence, and one patient died
of pelvic malignancy. One patient recurred locally and is alive and disease free
after surgical management. Brisk lymphocytic infiltrate was present pre-treatment
in 39% of 18 patients with evaluable tumor. Conclusions: Adjuvant concurrent
carboplatin and prone accelerated radiotherapy is a well-tolerated and promising
treatment of early stage TNBC. The observed 3% compares favorably with the
expected 30% recurrence rate within 1-4 y from treatment, warranting further
studies.
PMID- 28405498
TI - Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based
immunocytokine for combination cancer immunotherapy: Overcoming limitations of
aldesleukin and conventional IL-2-based immunocytokines.
AB - We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA
targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with
abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent
carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector
functions. Its molecular design aims to (i) avoid preferential activation of
regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii)
increase the therapeutic index of IL-2 therapy by (a) preferential retention at
the tumor by having a lower dissociation rate from CEA-expressing cancer cells
vs. IL-2R-expressing cells, (b) avoiding any FcgammaR-binding and Fc effector
functions and (c) reduced binding to endothelial cells expressing CD25; and (iii)
improve the pharmacokinetics, and thus convenience of administration, of IL-2.
The crystal structure of the IL2v-IL-2Rbetagamma complex was determined and CEA
IL2v activity was assessed using human immune effector cells. Tumor targeting was
investigated in tumor-bearing mice using 89Zr-labeled CEA-IL2v. Efficacy studies
were performed in (a) syngeneic mouse models as monotherapy and combined with
anti-PD-L1, and in (b) xenograft mouse models in combination with ADCC-mediating
antibodies. CEA-IL2v binds to CEA with pM avidity but not to CD25, and
consequently did not preferentially activate Tregs. In vivo, CEA-IL2v
demonstrated superior pharmacokinetics and tumor targeting compared with a wild
type IL-2-based CEA immunocytokine (CEA-IL2wt). CEA-IL2v strongly expanded NK and
CD8+ T cells, skewing the CD8+:CD4+ ratio toward CD8+ T cells both in the
periphery and in the tumor, and mediated single agent efficacy in syngeneic MC38
CEA and PancO2-CEA models. Combination with trastuzumab, cetuximab and
imgatuzumab, all of human IgG1 isotype, resulted in superior efficacy compared
with the monotherapies alone. Combined with anti-PD-L1, CEA-IL2v mediated
superior efficacy over the respective monotherapies, and over the combination
with an untargeted control immunocytokine. These preclinical data support the
ongoing clinical investigation of the cergutuzumab amunaleukin immunocytokine
with abolished CD25 binding for the treatment of CEA-positive solid tumors in
combination with PD-L1 checkpoint blockade and ADCC competent antibodies.
PMID- 28405499
TI - Combining therapeutic antibodies using basiliximab and etanercept for severe
steroid-refractory acute graft-versus-host disease: A multi-center prospective
study.
AB - Acute graft versus host disease (aGVHD) remains a major problem after allogeneic
hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD
involves corticosteroids. However, fewer than half of patients have a lasting
complete response. The long-term mortality rate of steroid-refractory aGVHD (SR
aGVHD) remains around 70%. To date, no consensus has been reached regarding the
optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi
center clinical trial to assess the efficacy and safety of a novel approach to
treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and
etanercept. Sixty-five patients with severe SR-aGVHD from six centers were
included. The median number of basiliximab infusions was 4 (range 2-11) and of
etanercept was 9 (range 2-12). At day 28 after starting the combination
treatment, overall response (complete and partial response: CR+PR) to second-line
treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were
100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively.
Patients >30-y old (p = 0.043, RR = 3.169), development of grades III-IV liver
aGVHD (p = 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p = 0.035,
RR = 4.02) were independent predictors for incomplete response. Combined
treatment with basiliximab and etanercept resulted in improved CR to visceral
aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001)
compared with classical salvage treatments. Our data suggest that the combination
of basiliximab and etanercept may constitute a promising new treatment option for
SR-aGVHD.
PMID- 28405500
TI - Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to
stimulate effector gammadelta T cells with antitumor activity.
AB - Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in
anticancer clinical trials due to their ability to upregulate pyrophosphate
accumulation promoting antitumor Vgamma9Vdelta2 T cells. The butyrophilin 3A
(BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important
structure contributing to Vgamma9Vdelta2 T cells stimulation. It has been
demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and
drive the activation of Vgamma9Vdelta2 T cells through conformational changes of
the extracellular domains. Moreover, BTN3A1 binding to the cytoskeleton, and its
consequent membrane stabilization, is crucial to stimulate the PAg-induced tumor
cell reactivity by human Vgamma9Vdelta2 T cells. Aim of this study was to
investigate the relevance of BTN3A1 in N-BPs-induced antitumor response in
colorectal cancer (CRC) and the cell types involved in the tumor
microenvironment. In this paper, we show that (i) CRC, exposed to Zol, stimulates
the expansion of Vdelta2 T lymphocytes with effector memory phenotype and
antitumor cytotoxic activity, besides sensitizing cancer cells to gammadelta T
cell-mediated cytotoxicity; (ii) this effect is partially related to BTN3A1
expression and in particular with its cellular re-distribution in the membrane
and cytoskeleton-associated fraction; (iii) BTN3A1 is detected in CRC at the
tumor site, both on epithelial cells and on tumor-associated fibroblasts (TAF),
close to areas infiltrated by Vdelta2 T lymphocytes; (iv) Zol is effective in
stimulating antitumor effector Vdelta2 T cells from ex-vivo CRC cell suspensions;
and (v) both CRC cells and TAF can be primed by Zol to trigger Vdelta2 T cells.
PMID- 28405501
TI - PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas.
AB - Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive
tumors, with high metastatic risk and relatively few efficient systemic
therapies. In the quest for new treatments, the immune system represents an
attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very
promising results in patients with solid tumors. PDL1 expression has been rarely
studied in STS, in small series only, by using immunohistochemistry (IHC), and
with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA
expression in 758 clinical STS samples retrospectively profiled using DNA
microarrays and RNAseq, and searched for correlations with clinicopathological
variables including metastasis-free survival (MFS) after surgery. PDL1 expression
was heterogeneous across the samples. PDL1-high samples (41%) were more
frequently leiomyosarcomas and liposarcomas, and showed more frequently a complex
genetic profile and a high-risk CINSARC signature. No correlation existed with
other clinicopathological features such as tumor site, depth, and pathological
tumor grade and size. In multivariate prognostic analysis, the PDL1-high class
was associated with shorter MFS, independently of the pathological type and the
CINSARC signature. Analysis of correlations with biological factors suggested the
existence in tumors of the PDL1-high class of a strong and efficient cytotoxic T
cell response, however associated with some degree of T-cell exhaustion and
negative regulation. In conclusion, we show that PDL1 expression refines the
prediction of metastatic relapse in operated localized STS, and that PD1/PDL1
blockade holds potential to improve patient survival by reactivating inhibited T
cells to increase the antitumor immune in PDL1-high tumors.
PMID- 28405502
TI - IL4-induced gene 1 promotes tumor growth by shaping the immune microenvironment
in melanoma.
AB - Amino acid catabolizing enzymes emerged as a crucial mechanism used by tumors to
dampen immune responses. The L-phenylalanine oxidase IL-4 induced gene 1 (IL4I1)
is expressed by tumor-associated myeloid cells of most solid tumors, including
melanoma. We previously provided the only evidence that IL4I1 accelerates tumor
growth by limiting the CD8+ T cell mediated immune response, in a mouse model of
melanoma cell transplantation. Here, we explored the role of IL4I1 in Ret mice, a
spontaneous model of melanoma. We found that IL4I1 was expressed by CD11b+
myeloid cells and that its activity correlated with disease aggressiveness. IL4I1
did not enhance tumor cell proliferation or angiogenesis, but orchestrated the
remodeling of the immune compartment within the primary tumor. Indeed, the
inactivation of IL4I1 limited the recruitment of polymorphonuclear myeloid
derived suppressor cells and enhanced the infiltration by Th1 and cytotoxic T
cells, thus delaying tumor development and metastatic dissemination. Accordingly,
human primary melanomas that were poorly infiltrated by IL4I1+ cells exhibited a
higher density of CD8+ T cells. Collectively, our findings strengthen the
rationale for therapeutic targeting of IL4I1 as one of the key immune regulators.
PMID- 28405503
TI - Genotoxic stress modulates the release of exosomes from multiple myeloma cells
capable of activating NK cell cytokine production: Role of HSP70/TLR2/NF-kB axis.
AB - Exosomes are a class of nanovesicles formed and released through the late
endosomal compartment and represent an important mode of intercellular
communication. The ability of anticancer chemotherapy to enhance the immunogenic
potential of malignant cells mainly relies on the establishment of the
immunogenic cell death (ICD) and the release of damage-associated molecular
patterns (DAMPs). Here, we investigated whether genotoxic stress could promote
the release of exosomes from multiple myeloma (MM) cells and studied the
immunomodulatory properties they exert on NK cells, a major component of the
antitumor immune response playing a key role in the immunosurveillance of MM. Our
findings show that melphalan, a genotoxic agent used in MM therapy, significantly
induces an increased exosome release from MM cells. MM cell-derived exosomes are
capable of stimulating IFNgamma production, but not the cytotoxic activity of NK
cells through a mechanism based on the activation of NF-kappaB pathway in a
TLR2/HSP70-dependent manner. Interestingly, HSP70+ exosomes are primarily found
in the bone marrow (BM) of MM patients suggesting that they might have a crucial
immunomodulatory action in the tumor microenvironment. We also provide evidence
that the CD56high NK cell subset is more responsive to exosome-induced IFNgamma
production mediated by TLR2 engagement. All together, these findings suggest a
novel mechanism of synergism between chemotherapy and antitumor innate immune
responses based on the drug-promotion of nanovesicles exposing DAMPs for innate
receptors.
PMID- 28405504
TI - PD-L1 (CD274) copy number gain, expression, and immune cell infiltration as
candidate predictors for response to immune checkpoint inhibitors in soft-tissue
sarcoma.
AB - Soft-tissue sarcomas (STS) are rare malignancies that account for 1% of adult
cancers and comprise more than 50 entities. Current therapeutic options for
advanced-stage STS are limited. Immune checkpoint inhibitors targeting the PD
1/PD-L1 signaling axis are being explored as new treatment modality in STS;
however, the determinants of response to these agents are largely unknown. Using
the sarcoma data set of The Cancer Genome Altas (TCGA) and an independent cohort
of untreated high-grade STS, we analyzed DNA copy number status and mRNA
expression of PD-L1 in a total of 335 STS cases. Copy number gains (CNG) were
detected in 54 TCGA cases (21.1%), of which 21 (8.2%) harbored focal PD-L1 CNG
and that were most prevalent in myxofibrosarcoma (35%) and undifferentiated
pleomorphic sarcoma (34%). In the untreated high-grade STS cohort, we detected
CNG in six cases (7.6%). Analysis of co-amplified genes identified a 5.6-Mb core
region comprising 27 genes, including JAK2. Patients with PD-L1 CNG had higher PD
L1 expression compared with STS without CNG (fold change, 1.8; p = 0.02), an
effect that was most pronounced in the setting of focal PD-L1 CNG (fold change,
3.0; p = 0.0027). STS with PD-L1 CNG showed a significantly higher mutational
load compared with tumors with a diploid PD-L1 locus (median number of mutated
genes; 58 vs. 40; p = 3.6E-06), and PD-L1 CNG were associated with inferior
survival (HR = 1.82; p = 0.025). In contrast, T-cell infiltrates quantified by
mRNA expression of CD3Z were associated with improved survival (HR = 0.88; p =
0.024) and consequently influenced the prognostic power of PD-L1 CNG, with low
CD3Z levels conferring poor survival in cases with PD-L1 CNG (HR = 1.8; p =
0.049). These data demonstrate that PD-L1 GNG and elevated expression of PD-L1
occur in a substantial proportion of STS, have prognostic impact that is
modulated by T-cell infiltrates, and thus warrant investigation as response
predictors for immune checkpoint inhibition.
PMID- 28405505
TI - MEDI1873, a potent, stabilized hexameric agonist of human GITR with regulatory T
cell targeting potential.
AB - Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is
part of a system of signals involved in controlling T-cell activation. Targeting
and agonizing GITR in mice promotes antitumor immunity by enhancing the function
of effector T cells and inhibiting regulatory T cells. Here, we describe
MEDI1873, a novel hexameric human GITR agonist comprising an IgG1 Fc domain, a
coronin 1A trimerization domain and the human GITRL extracellular domain (ECD).
MEDI1873 was optimized through systematic testing of different trimerization
domains, aglycosylation of the GITRL ECD and comparison of different Fc isotypes.
MEDI1873 exhibits oligomeric heterogeneity and superiority to an anti-GITR
antibody with respect to evoking robust GITR agonism, T-cell activation and
clustering of Fc gamma receptors. Further, it recapitulates, in vitro, several
aspects of GITR targeting described in mice, including modulation of regulatory T
cell suppression and the ability to increase the CD8+:CD4+ T-cell ratio via
antibody-dependent T-cell cytotoxicity. To support translation into a therapeutic
setting, we demonstrate that MEDI1873 is a potent T-cell agonist in vivo in non
human primates, inducing marked enhancement of humoral and T-cell proliferative
responses against protein antigen, and demonstrate the presence of GITR- and
FoxP3-expressing infiltrating lymphocytes in a range of human tumors. Overall our
data provide compelling evidence that MEDI1873 is a novel, potent GITR agonist
with the ability to modulate T-cell responses, and suggest that previously
described GITR biology in mice may translate to the human setting, reinforcing
the potential of targeting the GITR pathway as a therapeutic approach to cancer.
PMID- 28405506
TI - Oral delivery of tumor microparticle vaccines activates NOD2 signaling pathway in
ileac epithelium rendering potent antitumor T cell immunity.
AB - Exploiting gut mucosal immunity to design new antitumor vaccination strategy
remains unexplored. Tumor cell-derived microparticles (T-MP) are natural
biomaterials that are capable of delivering tumor antigens and innate signals to
dendritic cells (DC) for tumor-specific T cell immunity. Here, we show that T-MPs
by oral vaccination route effectively access and activate mucosal epithelium,
leading to subsequent antitumor T cell responses. Oral vaccination of T-MPs
generated potent inhibitory effect against the growth of B16 melanoma and CT26
colon cancer in mice, which required both T cell and DC activation. T-MPs, once
entering intestinal lumen, were mainly taken up by ileac intestinal epithelial
cells (IEC), where T-MPs activated NOD2 and its downstream MAPK and NF-kappaB,
leading to chemokine releasing, including CCL2, from IECs to attract CD103+
CD11c+ DCs. Furthermore, ileac IECs could transcytose T-MPs to the basolateral
site, where T-MPs were captured by those DCs for cross-presentation of loaded
antigen contents. Elucidating these molecular and cellular mechanisms highlights
T-MPs as a novel antitumor oral vaccination strategy with great potential of
clinical applications.
PMID- 28405507
TI - A review of the importance of immune responses in luminal B breast cancer.
AB - Historically, the immune environment was not considered an important target for
breast cancer treatment. However, the association of lymphocytic infiltrates in
triple negative and HER-2 over-amplified breast cancer subtypes with better
outcomes, has provoked interest in evaluating the role of the immune system in
the luminal B subtype that accounts for 39% of breast cancers and has a poor
patient prognosis. It is unknown which immunosuppressive cell types or molecules
(e.g., checkpoint molecules) are relevant, or where measurement is most
informative. We hypothesize that a profound immunosuppressive tumor and/or lymph
node milieu is prognostic and impacts on responses to therapies.
PMID- 28405508
TI - Antigen receptor-redirected T cells derived from hematopoietic precursor cells
lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor
capacities.
AB - Recent clinical studies indicate that adoptive T-cell therapy and especially
chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially
curative treatment for B-lineage hematologic malignancies. Currently, autologous
peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells
derived from healthy allogeneic donors may have several advantages; however, the
expected occurrence of graft versus host disease (GvHD) as a consequence of the
diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells
compromises this approach. Here, we generated T cells from cord blood
hematopoietic progenitor cells (HPCs) that were transduced to express an antigen
receptor (AR): either a CAR or a TCR with or without built-in CD28 co-stimulatory
domains. These AR-transgenic HPCs were culture-expanded on an OP9-DL1 feeder
layer and subsequently differentiated to CD5+CD7+ T-lineage precursors, to CD4+
CD8+ double positive cells and finally to mature AR+ T cells. The AR+ T cells
were largely naive CD45RA+CD62L+ T cells. These T cells had mostly germline
TCRalpha and TCRbeta loci and therefore lacked surface-expressed CD3/TCRalphabeta
complexes. The CD3- AR-transgenic cells were mono-specific, functional T cells as
they displayed specific cytotoxic activity. Cytokine production, including IL-2,
was prominent in those cells bearing ARs with built-in CD28 domains. Data sustain
the concept that cord blood HPC derived, in vitro generated allogeneic CD3- AR+ T
cells can be used to more effectively eliminate malignant cells, while at the
same time limiting the occurrence of GvHD.
PMID- 28405509
TI - Improved time to disease progression in the brain in patients with melanoma brain
metastases treated with concurrent delivery of radiosurgery and ipilimumab.
AB - Background: To identify the optimal sequencing and timing of immunotherapy (IT)
and stereotactic radiosurgery (SRS) for melanoma brain metastases (MBMs).
Methods: The elapsed days between IT and SRS were correlated with local control
(LC), regional brain control (RBC), time to CNS progression (TTPCNS), overall
survival (OS), and radiation necrosis (RN). Logistic regression and Cox
proportional models were used for statistical analysis. Results: Twenty-five
patients with 58 MBMs underwent SRS and IT. Median follow-up was 22.7 mo (3.1
77.9 mo). A median of 2 SRS treatments of 21 Gy (range 16-24 Gy) and 4 cycles of
Ipilimumab were delivered. SRS was delivered Before, After or Concurrently with
IT in 9, 5, and 11 patients, respectively; 8/25 received SRS <=30 d of IT and
17/25 were >30 d of IT. Median OS was 35.8 mo, 1- and 2-y OS was 83% and 64%,
respectively, and LC was 94.8%. By timing, RBC and TTPCNS were significantly
improved when SRS was delivered <=30 d of IT (75% vs 23.5%, p = 0.03 and median
not reached vs 5.7 mo, p = 0.02, respectively). By groups, Concurrent delivery
improved TTPCNS (p = 0.04). The rate of RN was 20.7% (12/58 lesions) and RN was
associated with improved OS (HR 0.21, p = 0.01). Conclusions: High OS was found
for MBM treated with SRS and IT compared to historical reports. A significant
association for improved RBC and TTPCNS was found when SRS was delivered
concurrently and within 30 d of IT. Occurrence of RN was higher than SRS alone
series but significantly associated with improved OS.
PMID- 28405510
TI - Correlation between previous treatment with BRAF inhibitors and clinical response
to pembrolizumab in patients with advanced melanoma.
AB - The optimal sequencing of targeted treatment and immunotherapy in the treatment
of advanced melanoma is a key question and prospective studies to address this
are ongoing. Previous observations suggest that treating first with targeted
therapy may select for more aggressive disease, meaning that patients may not
gain full benefit from subsequent immunotherapy. In a single-center retrospective
analysis, we investigated whether response to pembrolizumab was affected by
previous BRAF inhibitor therapy. A total of 42 patients with metastatic cutaneous
or mucosal melanoma who had received previous treatment with ipilimumab were
treated with pembrolizumab as part of the Italian expanded access program.
Sixteen of these patients had BRAF-mutated melanoma and had also been previously
treated with a BRAF inhibitor (vemurafenib or dabrafenib), while 26 had BRAF wild
type melanoma (no previous BRAF inhibitor). Patients with BRAF-mutant melanoma
who were previously treated with BRAF inhibitors had a significantly lower median
progression-free survival (3 [2.3-3.7] versus not reached [2-8+] mo; p = 0.001)
and disease control rate (18.6% versus 65.4%; p = 0.005) than patients with BRAF
wild-type, while there was also a trend toward a lower response rate (assessed
using immune-related response criteria) although this was not significantly
different between groups (12.5% versus 36.4%; p = 0.16). These data are
consistent with previous reports that BRAF inhibitor therapy may affect
subsequent response to immunotherapy.
PMID- 28405511
TI - NK cells control breast cancer and related cancer stem cell hematological spread.
AB - The growth and recurrence of a number of cancers is driven by a scarce population
of cancer stem cells (CSCs), which are resistant to most current therapies. It
has been shown previously that natural killer (NK) cells recognize human glioma,
melanoma, colon and prostate CSCs in vitro. We herein show that human and mouse
breast CSCs are also susceptible to NK cytotoxic activity in vitro. Moreover, CSC
induced autologous NK cell activation and expansion in vivo, which correlate with
the inhibition of CSC metastatic spread. These data suggest that NK cells control
CSC metastatic spread in vivo and that their use in breast cancer therapy may
well be fruitful.
PMID- 28405512
TI - High expression of PD-1 ligands is associated with kataegis mutational signature
and APOBEC3 alterations.
AB - Immunotherapy with checkpoint inhibitors, such as antibodies blocking the
programmed cell-death receptor-1 (PD-1), has resulted in remarkable responses in
patients having traditionally refractory cancers. Although response to PD-1
inhibitors correlates with PD-1 ligand (PD-L1 or PD-L2) expression, PD-1 ligand
positivity represents only a part of the predictive model necessary for selecting
patients predisposed to respond to immunotherapy. We used all genomic,
transcriptomic, proteomic and phenotypic data related to 8,475 pan-cancer samples
available in The Cancer Genome Atlas (TCGA) and conducted a logistic regression
analysis based on a large set of variables, such as microsatellite instability
(MSI-H), mismatch repair (MMR) alterations, polymerase delta (POLD1) and
polymerase epsilon (POLE) mutations, activation-induced/apolipoprotein-B editing
cytidine deaminases (AID/APOBEC) alterations, lymphocyte markers and mutation
burden estimates to determine independent factors that associate with PD-1 ligand
overexpression. PD-1 ligand overexpression was independently and significantly
correlated with overexpression of and mutations in APOBEC3 paralogs.
Additionally, while high tumor mutation burden and overexpression of PD-L1 have
been previously correlated with each other, we demonstrate that the specific
mutation pattern caused by APOBEC enzymes and called kataegis-rather than overall
mutation burden, MSI-H or MMR alterations-correlates independently with PD-L1/PD
L2 expression. These observations suggest that APOBEC3 alterations, APOBEC3
overexpression and kataegis play an important role in the regulation of PD-1
ligand overexpression, and thus, their relationship with immune checkpoint
inhibitor response warrants exploration.
PMID- 28405514
TI - Regulatory B cells promote graft-versus-host disease prevention and maintain
graft-versus-leukemia activity following allogeneic bone marrow transplantation.
AB - Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host
disease (GVHD). However, whether Bregs can alleviate acute GVHD without
compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we
evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model
and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of
Bregs prevents onset through inhibiting Th1 and Th17 differentiation and
expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the
suppression of acute GVHD but had no adverse effect on GVL activity. In the
clinical cohort study, a higher dose of Bregs in allografts was associated with a
lower cumulative incidence of acute GVHD but not with increased risk of relapse.
Our data demonstrate that Bregs can prevent acute GVHD and maintain GVL effects
and suggest that Bregs have potential as a novel strategy for acute GVHD
alleviation.
PMID- 28405513
TI - Tumor SQSTM1 (p62) expression and T cells in colorectal cancer.
AB - Evidence suggests that activation of autophagy in neoplastic cells potentiates
antitumor immunity through cross-presentation of tumor-associated antigens to T
cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein
is degraded by activated autophagy, and might enhance immune response to tumor
cells. We hypothesized that tumor SQSTM1 expression level might be inversely
associated with T-cell densities in colorectal carcinoma tissue. We evaluated
tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer
cases within the Nurses' Health Study and Health Professionals Follow-up Study.
Ordinal logistic regression analyses were conducted to assess the association of
tumor SQSTM1 expression with CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell density
in tumor tissue, controlling for potential confounders, including tumor status of
microsatellite instability, CpG island methylator phenotype, long interspersed
nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutations.
Tumor SQSTM1 expression level was inversely associated with FOXP3+ cell density
(ptrend = 0.006), but not with CD3+, CD8+, or CD45RO+ cell density (with the
adjusted alpha level of 0.01 for multiple hypothesis testing). For a unit
increase in quartile categories of FOXP3+ cell density, multivariable odds ratios
were 0.66 [95% confidence interval (CI), 0.45-0.98] for intermediate-level SQSTM1
expression, and 0.55 (95% CI, 0.36-0.83) for high-level SQSTM1 expression,
compared with low-level SQSTM1 expression. Tumor SQSTM1 expression is inversely
associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a
possible role of SQSTM1-expressing carcinoma cells on regulatory T cells in the
tumor microenvironment.
PMID- 28405515
TI - PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen
receptor T cells.
AB - In recent years, immunotherapies, such as those involving chimeric antigen
receptor (CAR) T cells, have become increasingly promising approaches to non
small-cell lung cancer (NSCLC) treatment. In this study, we explored the
antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and
mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we
generated patient-derived xenograft (PDX) mouse models of human NSCLC that
maintained the antigenic profiles of primary tumors. Next, we demonstrated the
expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation
of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against
NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T
cells could efficiently suppress NSCLC tumor growth in PDX mice and
synergistically eliminate PSCA+MUC1+ tumors when combined with MUC1-targeting CAR
T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both
promising CAR T cell targets in NSCLC and that the combinatorial targeting of
these antigens could further enhance the antitumor efficacy of CAR T cells.
PMID- 28405516
TI - Assessment of tumor-infiltrating TCRVgamma9Vdelta2 gammadelta lymphocyte
abundance by deconvolution of human cancers microarrays.
AB - Most human blood gammadelta cells are cytolytic TCRVgamma9Vdelta2+ lymphocytes
with antitumor activity. They are currently investigated in several clinical
trials of cancer immunotherapy but so far, their tumor infiltration has not been
systematically explored across human cancers. Novel algorithms allowing the
deconvolution of bulk tumor transcriptomes to find the relative proportions of
infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim
but in practice they fail to accurately recognize gammadelta T lymphocytes. Here,
by implementing machine learning from microarray data, we first improved the
computational identification of blood-derived TCRVgamma9Vdelta2+ gammadelta
lymphocytes and then applied this strategy to assess their abundance as tumor
infiltrating lymphocytes (gammadelta TIL) in ~10,000 cancer biopsies from 50
types of hematological and solid malignancies. We observed considerable inter
individual variation of TCRVgamma9Vdelta2+gammadelta TIL abundance both within
each type and across the spectrum of cancers tested. We report their prominence
in B cell-acute lymphoblastic leukemia (B-ALL), acute promyelocytic leukemia (M3
AML) and chronic myeloid leukemia (CML) as well as in inflammatory breast,
prostate, esophagus, pancreas and lung carcinoma. Across all cancers, the
abundance of alphabeta TILs and TCRVgamma9Vdelta2+ gammadelta TILs did not
correlate. alphabeta TIL abundance paralleled the mutational load of tumors and
positively correlated with inflammation, infiltration of monocytes, macrophages
and dendritic cells (DC), antigen processing and presentation, and cytolytic
activity, in line with an association with a favorable outcome. In contrast, the
abundance of TCRVgamma9Vdelta2+ gammadelta TILs did not correlate with these
hallmarks and was variably associated with outcome, suggesting that distinct
contexts underlie TCRVgamma9Vdelta2+ gammadelta TIL and alphabeta TIL
mobilizations in cancer.
PMID- 28405517
TI - Hematopoietic stem cell-derived myeloid and plasmacytoid DC-based vaccines are
highly potent inducers of tumor-reactive T cell and NK cell responses ex vivo.
AB - Because of the potent graft-versus-tumor (GVT) effect, allogeneic stem cell
transplantation (alloSCT) can be a curative therapy for hematological
malignancies. However, relapse remains the most frequent cause of treatment
failure, illustrating the necessity for development of adjuvant post-transplant
therapies to boost GVT immunity. Dendritic cell (DC) vaccination is a promising
strategy in this respect, in particular, where distinct biologic functions of
naturally occurring DC subsets, i.e. myeloid DCs (mDCs) and plasmacytoid DCs
(pDCs), are harnessed. However, it is challenging to obtain high enough numbers
of primary DC subsets from blood for immunotherapy due to their low frequencies.
Therefore, we present here an ex vivo GMP-compliant cell culture protocol for
generating different DC subsets from CD34+ hematopoietic stem and progenitor
cells (HSPCs) of alloSCT donor origin. High numbers of BDCA1+ mDCs and pDCs could
be generated, sufficient for multiple vaccination cycles. These HSPC-derived DC
subsets were highly potent in inducing antitumor immune responses in vitro.
Notably, HSPC-derived BDCA1+ mDCs were superior in eliciting T cell responses.
They efficiently primed naive T cells and robustly expanded patient-derived minor
histocompatibility antigen (MiHA)-specific T cells. Though the HSPC-pDCs also
efficiently induced T cell responses, they exhibited superior capacity in
activating NK cells. pDC-primed NK cells highly upregulated TRAIL and possessed
strong cytolytic capacity against tumor cells. Collectively, these findings
indicate that HSPC-derived DC vaccines, comprising both mDCs and pDCs, may
possess superior potential to boost antitumor immunity post alloSCT, due to their
exceptional T cell and NK cell stimulatory capacity.
PMID- 28405518
TI - Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive
margin of colorectal cancer liver metastases associated with improved survival.
AB - On a broader scale, T cell density and localization in colorectal cancer liver
metastases have prognostic and predictive implications. As T cell distribution at
higher resolutions has not been fully investigated, a detailed resolution
analysis of T cell distribution was performed. Patient tissues were divided into
10 um distance classes between the tumor border and adjacent normal liver.
Thereby, distinct density patterns of T cell localization in relation to the
malignant tissue could be detected. At a distance of 20 to 30 um to the tumor, a
decrease of CD3 T cells is common. Within this area, cytotoxic Granzyme B and
CD8+ T cells were found to be significantly reduced as well as CD163 macrophages
were increased and identified to be in close contact with T cells. Our data
suggests a physical or functional border within this region. Survival analysis
revealed improved overall survival in patients with high T cells numbers at the
direct tumor border. Interestingly, the decreased T cells in the 20 to 30 um
region were also found to be significantly associated with improved survival.
Consequently, the detailed localization of T cells, despite blockade, could be
associated with improved clinical outcome. The high-resolution analysis
represents new insights into relevant heterogenous T cell distributions
especially related to clinical responses. As the paradoxical observation of
localization-dependent prognostic relevance of T cell densities is only
detectable by detailed spatial analyses, this investigation of spatial profiles
at higher resolutions is suggested as a new biomarker for survival and response
to therapies.
PMID- 28405519
TI - The Interleukin (IL)-1R1 pathway is a critical negative regulator of PyMT
mediated mammary tumorigenesis and pulmonary metastasis.
AB - Breast cancer is the most common cancer in women and the second leading cause of
female cancer-related deaths worldwide. Inflammation is an established hallmark
of tumorigenesis and an important determinant of tumor outcome and response to
therapy. With advances in cancer immunotherapy, there is an urgent need to
dissect the contribution of specific immune effectors in cancer development.
Here, we genetically investigated the role of the Interleukin-1 (IL-1) receptor 1
(IL-1R1) pathway in breast cancer tumorigenesis and metastasis using the MMTV
PyMT mouse model. Our results indicate that IL-1R1 signaling suppresses mammary
tumor cell proliferation early in tumorigenesis and curbs breast cancer outgrowth
and pulmonary metastasis. We show that PyMT/Il1r1-/- mice had a higher primary
tumor burden and increased mortality rate compared with IL-1R1-sufficient PyMT
control mice. This phenotype was independent of the inflammatory caspases-1/-11
but driven by IL-1alpha, as PyMT/Il1a-/- mice phenocopied PyMT/Il1r1-/- mice.
Collectively, our results suggest that IL-1alpha-mediated IL-1R1 signaling is
tumor-suppressive in PyMT-driven breast cancer.
PMID- 28405520
TI - The immune molecular landscape of the B7 and TNFR immunoregulatory ligand
receptor families in head and neck cancer: A comprehensive overview and the
immunotherapeutic implications.
AB - The B7 family and tumor necrosis factor receptor (TNFR) superfamily play a vital
role in the T-cell co-stimulatory and co-inhibitory pathways, regulating T-cell
activation, tolerance, and exhaustion; therapeutic modulation of these pathways
is translated into effective new cancer treatments. Better understanding of the
immune molecular landscapes of the B7 and TNFR families would guide head and neck
immuno-oncology clinical research. We performed comprehensive molecular profiling
of 10 B7 and 6 TNFR family members in head and neck cancer. Over 20% of patients
had B7 and TNFR gene alterations. B7 gene amplifications were relatively more
common (3-11%) than TNFR gene amplifications (0-5%). Analysis of 496 sequenced
samples revealed that all genes were upregulated: B7 and TNFR mRNA were
upregulated in 158 cases (> 30%) and 83 cases (~15%), respectively. B7-H1 (PD-L1)
mRNA upregulation was the most common (~10%). Promoter methylation analysis
indicated an epigenetic basis for B7 and TNFR gene regulation (especially B7-H1,
which was relatively strongly correlated with promoter methylation). B7-H1
expression was significantly associated with worse overall survival, and its
expression was increased in cases with gene amplifications. Human papillomavirus
(HPV) status correlated significantly with B7-H1 alterations at genetic level.
Almost half (47.1%) of HPV-negative patients had deep or shallow B7-H1 deletion;
>90% of HPV-positive patients had diploid, copy number gain, or amplification of
B7-H1. This is the first study elucidating the immune molecular landscapes of the
B7 and TNFR families in head and neck cancer, providing a potential novel
rationale for clinical investigations.
PMID- 28405521
TI - Human papilloma virus load and PD-1/PD-L1, CD8+ and FOXP3 in anal cancer patients
treated with chemoradiotherapy: Rationale for immunotherapy.
AB - We examined the prognostic role of immune markers programmed cell death protein-1
(PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+
Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell
cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline
immunohistochemical expression of immune markers was correlated with
clinicopathologic characteristics, and cumulative incidence of local failure,
disease-free survival (DFS) and overall survival (OS) in 150 patients, also in
the context of human papilloma virus 16 (HPV16) DNA load and p16INK4a expression.
After a median follow-up of 40 mo (1-205 mo), the 5-y cumulative incidence of
local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker
expression was significantly more common in tumors with high HPV16 viral load. In
multivariant analysis, high CD8+ and PD-1+ TILs expression predicted for improved
local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p =
0.014, respectively). Also, high p16INK4a (p = 0.011) and PD-L1 (p = 0.033)
expression predicted for better local control, whereas high FOXP3+ Tregs (p =
0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with
superior DFS. Female sex and high HPV16 viral load correlated with favorable
outcome for all three clinical endpoints. The present data provide, for the first
time, robust explanation for the favorable clinical outcome of HPV16-positive
ASCC patients harboring strong immune cell infiltration. Our findings are
relevant for treatment stratification with immune PD-1/PD-L1 checkpoint
inhibitors to complement CRT and should be explored in a clinical trial.
PMID- 28405522
TI - Calreticulin and type I interferon: An unsuspected connection.
PMID- 28405523
TI - Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and
recruit Foxp3+ regulatory T cells in murine colon cancer.
AB - The colorectal tumor microenvironment contains a diverse population of myeloid
cells that are recruited and converted to immunosuppressive cells, thus
facilitating tumor escape from immunoediting. We have identified a genetically
and functionally distinct subset of dynamic bone marrow myeloid cells that are
characterized by histidine decarboxylase (HDC) expression. Lineage tracing in Hdc
CreERT2;R26-LSL-tdTomato mice revealed that in homeostasis, there is a strong
bias by HDC+ myeloid cells toward the CD11b+Ly6Ghi granulocytic lineage, which
was accelerated during azoxymethane/dextran sodium sulfate (AOM/DSS)-induced
colonic carcinogenesis. More importantly, HDC+ myeloid cells strongly promoted
colonic tumorigenesis, and colon tumor progression was profoundly suppressed by
diphtheria toxin A (DTA)-mediated depletion of HDC+ granulocytic myeloid cells.
In addition, tumor infiltration by Foxp3+ regulatory T cells (Tregs) was markedly
impaired following HDC+ myeloid cell depletion. We identified an HDC+ myeloid
derived Cxcl13/Cxcr5 axis that mediated Foxp3 expression and Treg proliferation.
Ablation of HDC+ myeloid cells or disruption of the Cxcl13/Cxcr5 axis by gene
knockdown impaired the production and recruitment of Tregs. Cxcl13 induction of
Foxp3 expression in Tregs during tumorigenesis was associated with Stat3
phosphorylation. Overall, HDC+ granulocytic myeloid cells affect CD8+ T cells
directly and indirectly through the modulation of Tregs and thus appear to play
key roles in suppressing tumoricidal immunity.
PMID- 28405525
TI - Obinutuzumab-mediated high-affinity ligation of FcgammaRIIIA/CD16 primes NK cells
for IFNgamma production.
AB - Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity
(ADCC), based on the recognition of IgG-opsonized targets by the low-affinity
receptor for IgG FcgammaRIIIA/CD16, represents one of the main mechanisms by
which therapeutic antibodies (mAbs) mediate their antitumor effects. Besides
ADCC, CD16 ligation also results in cytokine production, in particular, NK
derived IFNgamma is endowed with a well-recognized role in the shaping of
adaptive immune responses. Obinutuzumab is a glycoengineered anti-CD20 mAb with a
modified crystallizable fragment (Fc) domain designed to increase the affinity
for CD16 and consequently the killing of mAb-opsonized targets. However, the
impact of CD16 ligation in optimized affinity conditions on NK functional program
is not completely understood. Herein, we demonstrate that the interaction of NK
cells with obinutuzumab-opsonized cells results in enhanced IFNgamma production
as compared with parental non-glycoengineered mAb or the reference molecule
rituximab. We observed that affinity ligation conditions strictly correlate with
the ability to induce CD16 down-modulation and lysosomal targeting of receptor
associated signaling elements. Indeed, a preferential degradation of
FcepsilonRIgamma chain and Syk kinase was observed upon obinutuzumab stimulation
independently from CD16-V158F polymorphism. Although the downregulation of
FcepsilonRIgamma/Syk module leads to the impairment of cytotoxic function induced
by NKp46 and NKp30 receptors, obinutuzumab-experienced cells exhibit an increased
ability to produce IFNgamma in response to different stimuli. These data
highlight a relationship between CD16 aggregation conditions and the ability to
promote a degradative pathway of CD16-coupled signaling elements associated to
the shift of NK functional program.
PMID- 28405524
TI - Therapeutic efficacy of combined vaccination against tumor pericyte-associated
antigens DLK1 and DLK2 in mice.
AB - When compared with vascular cells in normal tissues, pericytes and vascular
endothelial cells (VEC) in tumor blood vessels exhibit altered morphology and
epigenetic programming that leads to the expression of unique antigens that allow
for differential recognition by CD8+ T cells. We have previously shown that the
Notch antagonist delta-like homolog 1 (DLK1) is a tumor pericyte-associated
antigen expressed in setting of melanoma and a range of carcinomas. In this
report, we show that therapeutic vaccination against DLK1 in murine models
results in slowed tumor growth, but also to the compensatory expression of the
DLK1 homolog, DLK2, by tumor-associated pericytes. Vaccines targeting both DLK1
and DLK2 resulted in superior antitumor benefits in association with improved
activation and recruitment of antigen-specific Type 1 CD8+ T cells, reduced
presence of myeloid-derived suppressive cells, T regulatory cell and tumor
vascular normalization. The antitumor efficacy of vaccines coordinately targeting
DLK1 and DLK2 was further improved by inclusion of PD-L1 blockade, thus defining
a combination immunotherapy theoretically suitable for the treatment of a broad
range of solid (vascularized) cancers.
PMID- 28405526
TI - Anti-VEGFR2-interferon-alpha2 regulates the tumor microenvironment and exhibits
potent antitumor efficacy against colorectal cancer.
AB - Interferon-alpha (IFNalpha) has multiple antitumor effects including direct
antitumor toxicity and the ability to potently stimulate both innate and adaptive
immunity. However, its clinical applications in the treatment of malignancies
have been limited because of short half-life and serious adverse reactions when
attempting to deliver therapeutically effective doses. To address these issues,
we fused IFNalpha2a to the anti-vascular endothelial growth factor and receptor 2
(VEGFR2) antibody JZA00 with the goal of targeting it to the tumor
microenvironment where it can stimulate the antitumor immune response. The fusion
protein, JZA01, is effective against colorectal cancer by inhibiting
angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune
response. Although JZA01 exhibited reduced IFNalpha2 activity in vitro compared
with native IFNalpha2, VEGFR2 targeting permitted efficient antiproliferative,
proapoptotic, antiangiogenesis, and immune-stimulating effects against the
colorectal tumors HCT-116 and SW620. JZA01 showed in vivo efficacy in NOD-SCID
mice-bearing established HCT-116 tumors. In conclusion, this study describes an
antitumor immunotherapy that is highly promising for the treatment of colorectal
cancer.
PMID- 28405528
TI - Synergy in Lignin Upgrading by a Combination of Cu-Based Mixed Oxide and Ni
Phosphide Catalysts in Supercritical Ethanol.
AB - The depolymerization of lignin to bioaromatics usually requires a
hydrodeoxygenation (HDO) step to lower the oxygen content. A mixed Cu-Mg-Al oxide
(CuMgAlO x ) is an effective catalyst for the depolymerization of lignin in
supercritical ethanol. We explored the use of Ni-based cocatalysts, i.e. Ni/SiO2,
Ni2P/SiO2, and Ni/ASA (ASA = amorphous silica alumina), with the aim of combining
lignin depolymerization and HDO in a single reaction step. While the silica
supported catalysts were themselves hardly active in lignin upgrading, Ni/ASA
displayed comparable lignin monomer yield as CuMgAlO x . A drawback of using an
acidic support is extensive dehydration of the ethanol solvent. Instead,
combining CuMgAlO x with Ni/SiO2 and especially Ni2P/SiO2 proved to be effective
in increasing the lignin monomer yield, while at the same time reducing the
oxygen content of the products. With Ni2P/SiO2, the lignin monomer yield was 53
wt %, leading to nearly complete deoxygenation of the aromatic products.
PMID- 28405527
TI - JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation
to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer.
AB - Human pancreatic cancer does not respond to immune check point blockade
immunotherapy. One key feature of pancreatic cancer is the association between
its progression and chronic inflammation. Emerging evidence supports a key role
for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing
the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T
lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL
activity in pancreatic cancer. We show that human pancreatic carcinomas express
high level of PD-L1 and exhibit low level of CTL infiltration. JAK-STAT inhibitor
Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL
infiltration to induce a Tc1/Th1 immune response in the tumor microenvironment in
an orthotopic pancreatic cancer mouse model. Ruxilitinib-mediated tumor
suppressive efficacy diminishes in T-cell-deficient mice. Pancreatic tumor grows
significantly faster in IFNgamma-deficient mice. However, neutralizing IFNgamma
does not alter tumor growth but diminishes Ruxolitinib-induced tumor suppression
in vivo, indicating that lymphocytes and IFNgamma are essential for Ruxolitinib
induced host antitumor immune response. Both type I and type II interferons
upregulate PD-L1 expression through the JAK-STAT signaling pathway in mouse
pancreatic tumor cells. Tumor cells respond to activated T cells by activating
STAT3. The inhibition of STAT3 downregulates immune suppressive cytokines
production by tumor cells, resulting in increased T cell activation and effector
function. Consequently, Ruxolitinib significantly improves the efficacy of anti
PD-1 immunotherapy. Our data demonstrate that Ruxolitinib is effective in the
inhibition of systemic inflammation in the tumor microenvironment and therefore
upregulates CTL infiltration and activation to overcome pancreatic cancer
resistance to anti-PD-1 immunotherapy.
PMID- 28405529
TI - Defining Health in the Era of Value-based Care: Lessons from England of Relevance
to Other Health Systems.
AB - The demand for healthcare is rising due to aging populations, rising chronic
disease prevalence, and technological innovations. There are currently more
effective and cost-effective interventions available than can be afforded within
limited budgets. A new way of thinking about the optimal use of resources is
needed. Ensuring that available resources are used for interventions that provide
outcomes that patient's most value, rather than a focus just on effectiveness and
cost-effectiveness, may help to ensure that resources are used optimally. Value
based healthcare puts what patients value at the center of healthcare. It helps
ensure that they receive the care that can provide them with outcomes they think
are important and that limited resources are focused on high-value interventions.
In order to do this, we need flexible definitions of 'health', personalized and
tailored to patient values. We review the current status of value-based health
care in England and identify lessons applicable to a variety of health systems.
For this, we draw upon the work of the National Institute for Health and Care
Excellence (NICE), the National Health Service (NHS), Right Care Initiative, and
our local experience in promoting value-based health care for specific conditions
in our region. Combining the best available evidence with open and honest
dialogue between patients, clinicians, and others, whilst requiring considerable
time and resources are essential to building a consensus around the value that
allows the best use of limited budgets. Values have been present in healthcare
since its beginnings. Placing value and values at the center of healthcare could
help to ensure available resources are used to provide the greatest possible
benefit to patients.
PMID- 28405530
TI - Osborne's Ligament: A Review of its History, Anatomy, and Surgical Importance.
AB - When discussing the pathophysiology of ulnar neuropathy, Geoffrey Vaughan Osborne
described a fibrous band that can be responsible for the symptoms seen in this
disorder. In this paper, we take a glimpse at the life of Osborne and review the
anatomy and surgical significance of Osborne's ligament. This band of tissue
connects the two heads of the flexor carpi ulnaris and thus forms the roof of the
cubital tunnel. To our knowledge, no prior publication has reviewed the history
of this ligament, and very few authors have studied its anatomy in any detail.
Therefore, the aim of the present paper is to elucidate this structure that is
often implicated and surgically transected to decompress the ulnar nerve at the
elbow.
PMID- 28405531
TI - Will the Meikirch Model, a New Framework for Health, Induce a Paradigm Shift in
Healthcare?
AB - Over the past decades, scientific medicine has realized tremendous advances. Yet,
it is felt that the quality, costs, and equity of medicine and public health have
not improved correspondingly and, both inside and outside the USA, may even have
changed for the worse. An initiative for improving this situation is value-based
healthcare, in which value is defined as health outcomes relative to the cost of
achieving them. Value-based healthcare was advocated in order to stimulate
competition among healthcare providers and thereby reduce costs. The approach may
be well grounded economically, but in the care of patients, "value" has ethical
and philosophical connotations. The restriction of value to an economic meaning
ignores the importance of health and, thus, leads to misunderstandings. We
postulate that a new understanding of the nature of health is necessary. We
present the Meikirch model, a conceptual framework for health and disease that
views health as a complex adaptive system. We describe this model and analyze
some important consequences of its application to healthcare. The resources each
person needs to meet the demands of life are both biological and personal, and
both function together. While scientific advances in healthcare are hailed, these
advances focus mainly on the biologically given potential (BGP) and tend to
neglect the personally acquired potential (PAP) of an individual person. Personal
growth to improve the PAP strongly contributes to meeting the demands of life.
Therefore, in individual and public health care, personal growth deserves as much
attention as the BGP. The conceptual framework of the Meikirch model supports a
unified understanding of healthcare and serves to develop common goals, thereby
rendering interprofessional and intersectoral cooperation more successful. The
Meikirch model can be used as an effective tool to stimulate health literacy and
improve health-supporting behavior. If individuals and groups of people involved
in healthcare interact based on the model, mutual understanding of and adherence
to treatments and preventive measures will improve. In healthcare, the Meikirch
model also makes it plain that neither pay-for-performance nor value-based
payment is an adequate response to improve person-centered healthcare. The
Meikirch model is not only a unifying theoretical framework for health and
disease but also a scaffold for the practice of medicine and public health. It is
fully in line with the theory and practice of evidence-based medicine, person
centered healthcare, and integrative medicine. The model offers opportunities to
self-motivate people to improve their health-supporting behavior, thereby making
preventive approaches and overall healthcare more effective. We believe that the
Meikirch model could induce a paradigm shift in healthcare. The healthcare
community is hereby invited to acquaint themselves with this model and to
consider its potential ramifications.
PMID- 28405532
TI - Spinal Schwannoma with Intradural Intramedullary Hemorrhage.
AB - Patients with spinal abnormalities infrequently present with intradural
intramedullary bleeding. The more common causes include spinal trauma,
arteriovenous malformations and saccular aneurysms of spinal arteries. On
occasion, spinal cord tumors either primary or metastatic may cause
intramedullary bleed with ependymoma of the conus medullaris. Spinal nerve sheath
tumors such as schwannomas only rarely cause intradural intramedullary bleed,
especially in the absence of spinal cord or nerve root symptoms. We report a case
of spinal intradural schwannoma presenting with acute onset of quadriparesis.
Cerebral angiography studies were negative but magnetic resonance imaging (MRI)
of the spine revealed a large hemorrhagic tumor in the thoracolumbar junction.
However, we suggest that the patients with intradural intramedullary bleed should
be evaluated for underlying spine disease.
PMID- 28405533
TI - Scalp Seeding Post Craniotomy and Radiosurgery for Solitary Brain Metastasis: A
Case Report and Systematic Review.
AB - BACKGROUND : Radiosurgery is being increasingly used post craniotomy for brain
metastasis, instead of whole-brain radiation. We report a case of scalp
metastasis following craniotomy and radiosurgery, along with a systematic review
of the literature. METHODS : Our patient was a 70-year-old male who presented
with a scalp metastasis, two years after craniotomy and radiosurgery, for a
solitary brain metastasis from esophageal carcinoma. Using Medline(r) (United
States National Library of Medicine, Bethesda, MD), we performed a systematic
review of the literature to identify cases of isolated scalp metastases following
craniotomy for brain lesions. RESULTS : The scalp metastasis was in close
proximity to the craniotomy site. Workup did not show any other site of active
disease. Biopsy confirmed it to be a metastasis from esophageal carcinoma. The
literature review did not yield any case of isolated scalp metastasis following
craniotomy and whole-brain radiotherapy or radiosurgery. However, it yielded six
cases of isolated scalp metastases following craniotomy for primary brain tumors.
CONCLUSION : Isolated scalp metastasis has not been reported following
craniotomy and whole-brain radiotherapy for brain metastases. Our patient likely
had surgical seeding during craniotomy. These surgically implanted cells could
not be ablated because the radiosurgery treatment volume does not cover the
surgical tract. Further research is needed to identify risk factors for surgical
seeding.
PMID- 28405534
TI - Improving the Standard of Orthopaedic Operation Documentation Using Typed
Proforma Operation Notes: A Completed Audit Loop.
AB - INTRODUCTION: The Royal College of Surgeons (RCS) published Good Surgical
Practice guidelines in 2008 and revised them in 2014. They outline the basic
standard that all surgical operation notes should meet. OBJECTIVES: To
retrospectively audit 57 typed orthopaedic operation notes from St. James's
Hospital in Dublin (from August to November 2015) against the RCS Good Surgical
Practice guidelines published in 2014. They were then compared with the
department's previous audit of handwritten notes to complete the audit loop.
MATERIALS AND METHODS: A total of 57 orthopaedic operation notes were audited by
a single reviewer. They were prospectively collected between August and November
2015. All notes were typed on the standard St. James's Hospital operation note
proforma. RESULTS: Of the surgeries, 89.5% were emergencies with 77.2% of them
being performed by trainees. All of the operation notes were typed and signed by
trainees. The procedure name, incision and closure details, tourniquet time (when
relevant), and postoperative instructions were documented in 100% of the notes.
In total, 80.7% had an operative diagnosis included while only 26.9% of the
documentation had prosthesis serial numbers. All of the typed notes were deemed
to be legible. CONCLUSION: The use of printed operation notes allows for improved
legibility when compared to typed notes. Documentation standards remained very
high in the same areas as the handwritten notes and a marked improvement was seen
in areas that had been poorly documented.
PMID- 28405535
TI - Signet Cell in the Brain: A Case Report of Leptomeningeal Carcinomatosis as the
Presenting Feature of Gastric Signet Cell Cancer.
AB - Malignant infiltration of pia and arachnoid mater, referred to as leptomeningeal
carcinomatosis (LMC), is a rare complication of gastric carcinoma. The most
common underlying malignancy in patients with LMC are leukemia, breast cancer,
lymphoma, and lung cancer. We report a case of gastric adenocarcinoma that
presented with LMC in the absence of overt gastrointestinal signs or symptoms. A
56-year-old Hispanic woman presented to the hospital with a three-week history of
intermittent headaches and visual blurring. An initial brain imaging showed
infarction in the distribution of right posterior inferior cerebellar artery
(PICA) along with communicating hydrocephalus. She underwent ventriculoperitoneal
(VP) shunt placement with improvement in her symptoms. Two months later she
presented again with deterioration in her mental status. Imaging studies and
cerebrospinal fluid (CSF) analysis confirmed the diagnosis of LMC. Further
studies determined the primary tumor to be signet ring cell gastric
adenocarcinoma. However, she did not have any preceding gastrointestinal
symptoms. In light of the poor prognosis, the patient's family proceeded with
comfort care measures. Our case portrays a rare presentation of gastric
adenocarcinoma with LMC without other distant organ metastatic involvement. It
also illustrates the occult nature of gastric carcinoma and signifies the
importance of neurologic assessment of patients, with or at risk of gastric
carcinoma. It also raises a theoretical concern for VP shunt as a potential
conduit of malignant cells from the abdomen to the central nervous system, which
may serve as an important susbtrate for future research.
PMID- 28405536
TI - An Unfortunate Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal
Gammopathy, and Skin Change (POEMS).
AB - POEMS syndrome is an acronym for polyneuropathy, organomegaly, endocrinopathy,
monoclonal gammopathy and skin changes, which is a rare paraneoplastic disease of
monoclonal plasma cells. A mandatory criterion to diagnose POEMS syndrome is the
presence of a monoclonal plasma cell dyscrasia in which plasma cell leukemia is
the most aggressive form. Early identification of the features of the POEMS
syndrome is critical for patients to identify an underlying plasma cell
dyscrasias and to reduce the morbidity and mortality of the disease by providing
early therapy. We present a case of a 64-year-old male who presented with non
specific symptoms and was found to have primary plasma cell leukemia, which was
part of his unfortunate POEMS syndrome.
PMID- 28405537
TI - Vascular Air Embolism During Bronchoscopy Procedures- Incidence, Pathophysiology,
Diagnosis, Management and Outcomes.
AB - Vascular air embolism (VAE) is a rare, but potentially fatal complication of
invasive medical or surgical procedures. It is a very rare complication of
bronchoscopy and is most frequently reported with therapeutic bronchoscopy with
Argon plasma coagulation (APC) or neodymium-doped yttrium aluminum garnet (Nd
YAG) laser. Despite being rare, as a result of its high chance of mortality and
morbidity, it is imperative that physicians have high clinical suspicion to allow
for early recognition and treatment. In this article, we provide a concise review
of the incidence, pathophysiology, diagnosis management and outcomes of air
embolism during bronchoscopy procedures.
PMID- 28405538
TI - Henoch-Schonlein Purpura Presenting as Severe Gastrointestinal and Renal
Involvement with Mixed Outcomes in an Adult Patient.
AB - Henoch-Schonlein purpura (HSP) is typically seen as a self-limiting disease in
children, but can present more severely in adults, especially when there is renal
involvement. Management of HSP in adults also remains a controversial topic with
very few studies evaluating available therapies. In this case, HSP presenting as
a combination of severe gastrointestinal involvement and a rapid decline in renal
function in an adult patient directed our therapy. The patient was a 48-year-old
Caucasian male with no known past medical history, who presented with a
combination of purpuric rash over the lower extremities, severe abdominal pain
with upper gastrointestinal bleeding and a rapidly increasing serum creatinine,
with hematuria. He initially underwent a skin biopsy, along with investigation
for other possible causes, including autoimmune and infectious etiologies, which
were negative. He was started on therapy for presumed HSP with intravenous
methylprednisolone. The skin biopsy, however, was not conclusive, and the patient
had no improvement in his clinical status. He then underwent a kidney biopsy that
was consistent with HSP nephritis (immunoglobulin A (IgA) predominant
glomerulonephritis with crescents), and esophagogastroduodenoscopy (EGD) that
showed mucosal inflammation, ulcerations, and stigmata of bleeding-findings that
were consistent with ischemia. Cyclophosphamide was added to the regimen at this
time. However, he had worsening abdominal pain, continued gastrointestinal
bleeding, now with hematochezia, and also worsening renal function that required
dialysis. Plasmapheresis was then initiated on days alternating with dialysis.
This resulted in the improvement of his gastrointestinal symptoms, but no
recovery was seen of his renal function, and the patient required outpatient
dialysis. This case report exhibits the unique presentation of severe
gastrointestinal (GI) manifestations and rapid progression to renal failure in an
adult patient with partial resolution of his severe manifestation after therapy
was escalated as above. There was no established protocol that guided this
therapy, which reflects the need for more studies on adult HSP.
PMID- 28405539
TI - Quantifying biomass consumption and carbon release from the California Rim fire
by integrating airborne LiDAR and Landsat OLI data.
AB - Quantifying biomass consumption and carbon release is critical to understanding
the role of fires in the carbon cycle and air quality. We present a methodology
to estimate the biomass consumed and the carbon released by the California Rim
fire by integrating postfire airborne LiDAR and multitemporal Landsat Operational
Land Imager (OLI) imagery. First, a support vector regression (SVR) model was
trained to estimate the aboveground biomass (AGB) from LiDAR-derived metrics over
the unburned area. The selected model estimated AGB with an R2 of 0.82 and RMSE
of 59.98 Mg/ha. Second, LiDAR-based biomass estimates were extrapolated to the
entire area before and after the fire, using Landsat OLI reflectance bands,
Normalized Difference Infrared Index, and the elevation derived from LiDAR data.
The extrapolation was performed using SVR models that resulted in R2 of 0.73 and
0.79 and RMSE of 87.18 (Mg/ha) and 75.43 (Mg/ha) for the postfire and prefire
images, respectively. After removing bias from the AGB extrapolations using a
linear relationship between estimated and observed values, we estimated the
biomass consumption from postfire LiDAR and prefire Landsat maps to be 6.58 +/-
0.03 Tg (1012 g), which translate into 12.06 +/- 0.06 Tg CO2e released to the
atmosphere, equivalent to the annual emissions of 2.57 million cars.
PMID- 28405540
TI - Markedly Improved Success Rate of Endoscopically Assisted Third Ventriculostomy
Is Achieved by Routine Placement of External Lumbar Drain.
AB - Hydrocephalus is a major cause of patient decreased quality of life and high
health care financial burden in the United States and throughout the world. The
placement of ventricular shunts (ventriculoperitoneal shunt) has proven to be a
safe treatment for hydrocephalus, but it is associated with a high complication
rate leading to a lower quality of life and continued financial burden for
patients, their families, and society as a whole. The endoscopically assisted
third ventriculostomy (ETV) has been practiced as an alternative to ventricular
shunting since the 1990s. Success rates vary widely and there are many factors
which contribute to the varying success rates. The ETV procedure has the
potential to alleviate much of the overall quality of life issues and some of the
financial burdens associated with hydrocephalus provided success rates can be
increased and the procedure and management techniques are adopted more widely.
Common techniques have been published in the past which report associated
improvements in success rates amongst individual surgeons. Here, we report a
novel perioperative technique and management strategy that displays a higher than
reported success rate. Our methods and results show potential to significantly
improve overall ETV success rates if reproduced and subsequently adopted widely.
We retrospectively studied records of 24 adult patients with hydrocephalus who
were treated with an ETV procedure. Routinely, we placed an external lumbar drain
postoperatively which was continued for a minimum of 2 days. There was a 95.8%
success rate at 30 days. The overall success rate was 83.3%. This is
significantly higher than the average of the predicted success scores calculated
by the ETV success scoring system (71.8%). It is also significantly higher than
previous studies' reported ETV success rates in adults. We propose additional
similar studies to be performed to test the reproducibility of increased success
rates using our technique, ideally through a prospective, randomized, multicenter
trial.
PMID- 28405541
TI - It's Rare So Be Aware: Pleuropulmonary Blastoma Mimicking Congenital Pulmonary
Airway Malformation.
AB - Pleuropulmonary blastoma (PPB) is a rare aggressive malignant tumor of infancy
and early childhood. The tumor arises in the lung and pleura and is regarded as a
pulmonary dysontogenetic or embryonic neoplasm. Four types are defined in
literature. Type I PPB is a rare, cystic lung neoplasm in infants characterized
by subtle malignant changes and a good prognosis. Recurrences after type I PPB
are usually advanced with a poor prognosis. We report this case to increase
awareness about this entity so that the pediatricians, pediatric surgeons,
radiologist, and pathologist recognize it early.
PMID- 28405542
TI - Monitoring of endoscope reprocessing with an adenosine triphosphate (ATP)
bioluminescence method.
AB - Background: The arising challenges over endoscope reprocessing quality proposes
to look for possibilities to measure and control the process of endoscope
reprocessing. Aim: The goal of this study was to evaluate the feasibility of
monitoring endoscope reprocessing with an adenosine triphosphate (ATP) based
bioluminescence system. Methods: 60 samples of eight gastroscopes have been
assessed from routine clinical use in a major university hospital in Germany.
Endoscopes have been assessed with an ATP system and microbial cultures at
different timepoints during the reprocessing. Findings: After the bedside flush
the mean ATP level in relative light units (RLU) was 19,437 RLU, after the manual
cleaning 667 RLU and after the automated endoscope reprocessor (AER) 227 RLU.
After the manual cleaning the mean total viable count (TVC) per endoscope was
15.3 CFU/10 ml, and after the AER 5.7 CFU/10 ml. Our results show that there are
reprocessing cycles which are not able to clean a patient used endoscope.
Conclusion: Our data suggest that monitoring of flexible endoscope with ATP can
identify a number of different influence factors, like the endoscope condition
and the endoscopic procedure, or especially the quality of the bedside flush and
manual cleaning before the AER. More process control is one option to identify
and improve influence factors to finally increase the overall reprocessing
quality, best of all by different methods. ATP measurement seems to be a valid
technique that allows an immediate repeat of the manual cleaning if the ATP
results after manual cleaning exceed the established cutoff of 200 RLU.
PMID- 28405543
TI - Imaging of Renal Medullary Carcinoma.
AB - Renal medullary carcinoma (RMC) is a rare, highly aggressive tumor recognized as
an independent pathological entity. African-descent adolescents and young adults
with sickle cell hemoglobinopathy are the most affected groups. This rare subtype
of renal cell carcinoma has its own morphogenetic and pathological
characteristics. The major clinical manifestations include gross hematuria,
abdominal or flank pain, and weight loss. The prognosis is very poor, with 95% of
cases diagnosed at an advanced stage of the disease. In this review, we summarize
the morphologic and dynamic characteristics of RMC under various imaging
modalities such as ultrasound, computed tomography, and magnetic resonance.
Differential diagnosis and management strategies are also discussed.
PMID- 28405544
TI - Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A
Retrospective Analysis.
AB - Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC)
receive a second-line therapy. Therefore, the choice at each subsequent treatment
line remains an important issue. In this retrospective study, we sought to
identify pretreatment clinical parameters that could predict the likelihood of a
patient receiving a second-line therapy. One hundred and sixty-one mRCC patients
who received targeted therapy were evaluated. Descriptive statistics, Kaplan
Meier overall survival (OS), Cox regression, and binary logistic regression
models were used for data analysis. Second-line therapy was given to 105 patients
(65%). Patients with grade 1 tumor received second-line therapy more frequently
than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly
different between patients receiving, or not receiving, second-line treatment.
Median OS was significantly superior in patients receiving second-line therapy
(32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients
with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009),
and in patients without early tumor progression (41 versus 11 months; HR, 5.04;
95% confidence interval [CI], 3.06-8.31; P < 0.001). In binary logistic
regression, we identified early progression to be significantly associated with a
higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01
6.21; P = 0.048). This study hypothesizes that pretreatment grade and early
progression are predictive parameters for the selection of patients for second
line therapy.
PMID- 28405545
TI - Maslinic Acid Inhibits Proliferation of Renal Cell Carcinoma Cell Lines and
Suppresses Angiogenesis of Endothelial Cells.
AB - Despite the introduction of many novel therapeutics in clinical practice,
metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As
red and processed meat are considered risk factors for RCC, and a vegetable-rich
diet is thought to reduce this risk, research into plant-based therapeutics may
provide valuable complementary or alternative therapeutics for the management of
RCC. Herein, we present the antiproliferative and antiangiogenic effects of
maslinic acid, which occurs naturally in edible plants, particularly in olive
fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN,
Caki-1, and SN12K1), endothelial cells (human umbilical vein endothelial cell
line [HUVEC]), and primary cultures of kidney proximal tubular epithelial cells
(PTEC) were treated with maslinic acid. Maslinic acid was relatively less toxic
to PTEC when compared with RCC under similar experimental conditions. In RCC cell
lines, maslinic acid induced a significant reduction in proliferation,
proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid
induced a significant reduction in capillary tube formation in vitro and vascular
endothelial growth factor. This study provides a rationale for incorporating a
maslinic acid-rich diet either to reduce the risk of developing kidney cancer or
as an adjunct to existing antiangiogenic therapy to improve efficacy.
PMID- 28405546
TI - Arthropathy in Dermatology: A Comprehensive Review.
AB - Dermatology and rheumatology are two specialties that deal with significant
overlap. In this context, it is important that the dermatologists acquaint
themselves with conditions presenting with arthropathy. As the first step, it is
essential to know whether the origin of musculoskeletal symptom is articular or
extra-articular; inflammatory or noninflammatory; acute or chronic; oligo- or
poly-articular. This will help in narrowing down the differential diagnoses as
well as in better correlation with the cutaneous symptoms. In this review, we
discuss the skin and articular manifestations of common inflammatory and
noninflammatory arthropathies including rheumatoid arthritis,
spondyloarthropathies, connective tissue disorders, vasculitis, crystal
arthropathies, infective arthritis, arthritis associated with degenerative,
endocrine and metabolic conditions, etc. We have also added a section on the
common cutaneous features associated with the treatment of rheumatologic
diseases. A basic understanding of the joint pathologies and associated skin
changes will help a long way in the better management of these conditions.
PMID- 28405547
TI - Autologous Serum and Plasma Skin Tests in Chronic Spontaneous Urticaria: A
Reappraisal.
AB - AIM: The objective of this study was to assess autologous serum skin test (ASST)
vs autologous plasma skin test (APST) response in chronic spontaneous urticaria
(CSU) patients and study the significance of intensity of positive responses in
relation to clinicoepidemiological parameters. MATERIALS AND METHODS: One hundred
CSU patients and 100 age and sex-matched controls were recruited. The demographic
and clinical features were recorded in all patients and routine investigations
were performed. ASST and APST tests were performed as per the standard
guidelines. RESULTS: The mean duration of illness was 4.85 +/- 5.07 years, 90%
patients were APST (+), 68% ASST (+), and 22 patients were only APST (+).
Positive predictive value (PPV) of ASST and APST was 90.7% and 95.7%,
respectively. A significant inverse association was seen between thyroid status
and serum IgE levels with APST and ASST positivity. CONCLUSION: APST appears to
have better PPV and high intensity of positive response on autologous tests, and
correlates with ANA positivity and angioedema.
PMID- 28405548
TI - Clinicoepidemiological and Mycological Study of Tinea Capitis in the Pediatric
Population of Kashmir Valley: A Study from a Tertiary Care Centre.
AB - BACKGROUND: Tinea capitis is a superficial fungal infection that predominantly
affects the pediatric population. The etiological factors vary from region to
region, and the exact incidence remains obscure. The clinicoepidemiological and
mycological aspects of this dermatophytosis were studied in a tertiary care
centre in Kashmir valley. AIM: To determine the clinicoepidemiological aspects
and mycological findings of dermatophytes involved in tinea capitis cases in
Kashmir valley. MATERIALS AND METHODS: Wood's lamp examination, KOH examination,
and fungal culture were performed in one hundred fifty clinically diagnosed cases
of tinea capitis with patients' age upto 14 years over a period of 6 months. The
epidemiological factors associated with the disease were also evaluated. RESULTS:
Tinea capitis was predominant in the 3-6 and 6-9 years age groups with a male
preponderance. Grey patch tinea capitis was the most common variant. KOH
positivity was 76%, and Trichophyton tonsurans was the most common fungal
isolate. CONCLUSION: Tinea capitis is a very common fungal infection in our
setting. Early detection and diagnosis is mandatory to prevent its spread in the
community as well as the development of scarring alopecia in the affected
individual.
PMID- 28405549
TI - Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical
Study.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine
disorders in women, affecting 5-10% of reproductive-aged women. The dermatologic
manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic
alopecia, and acanthosis nigricans, are among the cardinal manifestations of
PCOS. AIM: To study the incidence and prevalence of various cutaneous
manifestations in patients with PCOS and to correlate these skin manifestations
with hormonal changes. SETTINGS AND DESIGN: This study was conducted at a
dermatology centre over a period of 1 year from November 2012 to 2013. MATERIALS
AND METHODS: The present study included 100 women diagnosed to have PCOS.
Hormonal analysis as well as radiological assessment was done in all the cases.
Cutaneous manifestations were ascertained and inferences were drawn. STATISTICAL
ANALYSIS: Statistical analysis was carried out by the Chi-square test and
independent samples t-test. Statistical significance was determined at a level of
P < 0.05. RESULTS: In our study, the prevalence of hirsutism, acne, female
pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was
78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively. CONCLUSION: Dermatologic
manifestations of PCOS play a significant role in making the diagnosis and
constitute a substantial portion of the symptoms experienced by women with this
syndrome.
PMID- 28405550
TI - Assembling a Hand-Held Trichotillometer and Determination of Epilation Force in
Normal Individuals.
AB - AIM: To assemble a simple, inexpensive hand-held trichotillometer and to
determine the epilation force (EF) required to pluck the anagen hair and telogen
hair from four regions of the scalp in healthy volunteers. MATERIALS AND METHODS:
A simple hand-held trichotillometer was assembled by modifying a laboratory
spring balance, and the instrument was calibrated after attachments. EF was
measured in 30 healthy individuals on four regions of the scalp. RESULTS: A total
of 30 volunteers were included in the study, among them 15 were males and 15 were
females. A total of 1200 hairs were examined. The mean EF in our study was 70.15
grams (g). The mean EF required to pluck the anagen hair was 86.61 g and telogen
hair was 53.69 g. CONCLUSION: The assembled- hand held trichotillometer is a
simple and reliable device. Tricotillometer is a useful device to measure the EF
in various physiological and pathological conditions and may have diagnostic,
prognostic, and therapeutic value in various hair diseases.
PMID- 28405551
TI - Spectrum of Lip Lesions in a Tertiary Care Hospital: An Epidemiological Study of
3009 Indian Patients.
AB - AIM: Large-scale population-based screening studies have identified lip lesions
to be the most common oral mucosal lesions; however, few studies have been
carried out to estimate the prevalence of lip lesions exclusively. The aim of
present study is to highlight the diversity of lip lesions and determine their
prevalence in an unbiased Indian population. MATERIALS AND METHODS: Lip lesions
were selected from 3009 patients who visited the department over a period of 3
years (January 2012 to December 2014). Age, sex, location of lip lesions, a
detailed family and medical history, along with the history of any associated
habit was recorded. Biopsy was carried out in necessary cases to reach a final
diagnosis. The pathologies of the lip were classified based on the etiology.
RESULTS: Among 3009 patients, 495 (16.5%) had lip lesions ranging from 4 years to
85 years with a mean age of 39.7 years. There were 309 (62.4%) males and 185
(31.9%) females. Lower lip was the most affected region (54.1%) followed by the
corner of the mouth (30.9%) and upper lip (11.7%). In 3.2% of the cases, both the
lips were involved. Of the 495 lip lesions, the most common were Potentially
Malignant Disorders (PMDs) (37.4%), herpes labialis (33.7%), mucocele (6.7%),
angular cheilitis (6.1%), and allergic and immunologic lesions (5.7%).
CONCLUSION: Lip lesions may act as an indicator for the presence of an underlying
systemic disease. PMDs and infections were the most common lip lesions in the
present study.
PMID- 28405552
TI - Over-the-counter and Prescription Medications for Acne: A Cross-Sectional Survey
in a Sample of University Students in Saudi Arabia.
AB - INTRODUCTION AND BACKGROUND: Acne is a very common dermatological condition found
among the adolescent population in Saudi Arabia. Many patients with acne try
various forms of self-medication, over the counter medicines (OTC), and
prescription medicines for the same. MATERIALS AND METHODS: This was a cross
sectional study among university students in the Kingdom of Saudi Arabia (KSA). A
validated questionnaire was distributed to a convenience sample of university
students to evaluate their knowledge and attitudes towards OTC (mainly) as well
as prescription medicine for acne. Chi-square and multiple logistic regression
tests were used for comparisons between groups. RESULTS: Four hundred and twenty
valid, completed questionnaires were obtained. A total of 220 (52.4%) used some
type of OTC medications at least once, where as 108 (25.7%) used prescription
medicines and 92 (21.9%) used both. The most common OTC medications used were
cleansers by 250 participants (41.9%). Among prescription medicines, the most
common were topical and oral antibiotics (11.4%). Bivariate and multivariate
analysis showed that females are statistically more likely to use OTC medicines
compared to males (Odds ratio: 1.7). CONCLUSION: The use of self-medications and
OTC medications is common among university students in KSA. The most common OTC
medicine used for acne was cleanser.
PMID- 28405553
TI - Lyme Disease: A Case Report with Typical and Atypical Lesions.
AB - Lyme disease is a multisystem infectious disease caused by the spirochete
"Borrelia burgdorferi," which is transmitted by "Ixodes" tick, with skin being
the most common and earliest organ to be affected. Diagnosis of erythema
chronicum migrans (ECM), which is the characteristic lesion of early disease, may
help in early treatment and prevention of complications. Here, we are reporting a
case of Lyme disease in a 10-year-old young boy from a non-endemic zone of
Himachal Pradesh, who presented with typical as well as atypical ECM lesions. The
clinical diagnosis was confirmed serologically, and the child was treated
successfully with doxycycline.
PMID- 28405554
TI - Arteriovenous Malformation Underlying a Plexiform Neurofibroma: An Unusual
Presentation.
AB - Vascular abnormalities associated with neurofibromatosis type 1 are well
described in the literature, however, arteriovenous malformation is a very rare
finding in neurofibromatosis type 1. We report the case of an 11-year-old girl
who presented with a soft mass on the right flank. Provisional diagnosis of
plexiform neurofibroma was made on the basis of clinical and histological
observations. Because the lesion was warm on palpation, imaging studies were
performed to evaluate further and arteriovenous malformation was detected
underlying the plexiform neurofibroma. This report emphasizes the importance of
careful examination and proper investigations of the plexiform neurofibroma prior
to treatment strategies to avoid future complications. The rarity of plexiform
neurofibroma in association with arteriovenous malformation at the same site was
also highlighted in this report.
PMID- 28405555
TI - Linear and Whorled Nevoid Hypermelanosis with Depigmentation.
AB - Linear and whorled nevoid hypermelanosis (LWNH) is a rare disorder of
pigmentation characterized by hyperpigmented macules in a linear or whorled
streaky configuration. Lesions are distributed mainly on the trunk and
extremities, sparing the palms, soles, and mucosae. Depigmentation occurring in
the pre-existing whorls has not been reported till date. Herein, we report one
such rare case of familial LWNH with depigmentation.
PMID- 28405556
TI - Multiple Basal Cell Carcinomas in a Patient of Oculocutaneous Albinism.
PMID- 28405557
TI - Dermographic Urticaria Induced by Long-Pulsed Diode Laser-Assisted Epilation:
Rare Etiology of a Common Eruption.
PMID- 28405558
TI - Sarcomatoid Carcinoma of the Hard Palate: An Unusual Cause of Palatal Ulcer.
PMID- 28405559
TI - A Sporadic Case of Ichthyosis Hystrix: Curth and Macklin Type.
PMID- 28405561
TI - Nevoid Hypertrichosis in a Pre-Adolescent Girl.
PMID- 28405560
TI - Acanthoma Fissuratum: Lest we Forget.
PMID- 28405562
TI - Extensive Giant Tuberous Xanthomas in a 12-Year-Old Boy.
PMID- 28405563
TI - Minoxidil-Induced Hypertrichosis in a Child with Alopecia Areata.
PMID- 28405564
TI - Laugier-Hunziker Syndrome in a Young Female.
PMID- 28405565
TI - Nevoid Psoriasis Coexisting with Verrucous Epidermal Nevus.
PMID- 28405566
TI - SkIndia Quiz 34: Asymptomatic Swelling over an Old Forehead Scar.
PMID- 28405567
TI - SkIndia Quiz 35: A Girl with Multiple Papules.
PMID- 28405568
TI - SkIndia Quiz 36: A Phantasmagoric Lesion: A Face for Thought.
PMID- 28405569
TI - Plexiform Neurofibroma Overlying Giant Cafe-au-lait Macule.
PMID- 28405570
TI - Case of Unilateral Temporal Triangular Alopecia.
PMID- 28405571
TI - A Dermoscopic Diagnosis and Activity Evaluation of Frontal Fibrosing Alopecia in
an Indian Lady.
PMID- 28405572
TI - Emerging role of nanoemulsions in oral health management.
PMID- 28405573
TI - Spherical crystallization: A technique use to reform solubility and flow property
of active pharmaceutical ingredients.
AB - Tablets have been choice of manufacturers over the years due to their
comparatively low cost of manufacturing, packaging, shipping, and ease of
administration; also have better stability and can be considered virtually tamper
proof. A major challenge in formulation development of the tablets extends from
lower solubility of the active agent to the elaborated manufacturing procedures
for obtaining a compressible granular material. Moreover, the validation and
documentation increases, as the numbers of steps increases for an industrially
acceptable granulation process. Spherical crystallization (SC) is a promising
technique, which encompass the crystallization, agglomeration, and spheronization
phenomenon in a single step. Initially, two methods, spherical agglomeration, and
emulsion solvent diffusion, were suggested to get a desired result. Later on, the
introduction of modified methods such as crystallo-co-agglomeration, ammonia
diffusion system, and neutralization techniques overcame the limitations of the
older techniques. Under controlled conditions such as solvent composition, mixing
rate and temperature, spherical dense agglomerates cluster from particles.
Application of the SC technique includes production of compacted spherical
particles of drug having improved uniformity in shape and size of particles, good
bulk density, better flow properties as well as better solubility so SC when used
on commercial scale will bring down the production costs of pharmaceutical tablet
and will increase revenue for the pharmaceutical industries in the competitive
market. This review summarizes the technologies available for SC and also
suggests the parameters for evaluation of a viable product.
PMID- 28405574
TI - Formulation and evaluation of transdermal drug delivery of topiramate.
AB - BACKGROUND: Transdermal drug delivery system (TDDS) was designed to sustain the
release and improve the bioavailability of drug and patient compliance. Among the
various types of transdermal patches, matrix dispersion type systems disperse the
drug in the solvent along with the polymers and solvent is allowed to evaporate
forming a homogeneous drug-polymer matrix. The objective of the present study was
to design and formulate TDDS of topiramate (TPM) and to evaluate their extended
release in vitro and ex vivo. MATERIALS AND METHODS: In the present study, an
attempt has been made to develop a matrix-type transdermal therapeutic system
comprising TPM with different ratios of hydrophilic and hydrophobic polymeric
combinations using solvent casting technique. RESULTS: The physicochemical
compatibility of the drug and the polymers was studied by Fourier transform
infrared spectroscopy. The results obtained showed no physical-chemical
incompatibility between the drug and the polymers. The patches were further
subjected to various physical evaluations along with the ex vivo permeation
studies using pig ear skin. CONCLUSIONS: On the basis of results obtained from
the physical evaluation and ex vivo studies the patches containing the polymers,
that is, Eudragit L 100 and polyvinylpyrrolidone, with oleic acid as the
penetration enhancer were considered as the best formulations for the transdermal
delivery of TPM.
PMID- 28405575
TI - Factorial analysis of the binding properties of acetylated ginger starch in
metronidazole tablet formulations.
AB - INTRODUCTION: The delivery of drug is often affected by formulation processes and
the excipients used in the formulation. MATERIALS AND METHODS: A 23 factorial
analysis was used in this study to evaluate the effect of acetylated ginger
starch (AGS) (Zingiber officinale) as a binder in metronidazole tablets, in
comparison to corn starch (CS) BP. The individual and interacting effects of
variables (binder type X1, binder concentration X2, and compression pressure X3)
used on tablet properties such as friability, crushing strength, crushing
strength friability ratio (CSFR), disintegration and crushing strength
friability/disintegration time ratio (CSFR/DT) were determined. The effect of
these binders on the granule properties using Hausner's ratio, Carr's index (CI),
angle of repose, and densities as response parameters was also determined.
RESULTS: Granules prepared with AGS had high densities and small granule sizes
when compared with those containing CS. Granules containing CS have better flow
properties. X1 (binder type) has a significant effect on the crushing strength of
the tablet. It also had the highest effects on CSFR and CSFR/DT. The combination
of XIX3 had the highest effect on crushing strength and DT. CONCLUSION: This
study shows that, in formulations, care must be taken in choosing the excipients
and the process parameters required for the formulation since these can affect
the delivery of the drug individually or in combination. AGS could be useful as a
binder when a tablet with low crushing strength and fast disintegration is
desired.
PMID- 28405576
TI - Evaluation of anti-diabetic activity of AHPL/AYTAB/0513 tablet in streptozotocin
induced diabetes in rats.
AB - BACKGROUND: Diabetes is a chronic, progressive disease associated with several
complications leading to significant mortality and morbidity. Limitations and
drawbacks of the conventional treatment generate need for safer, effective
complimentary therapies to prevent complications, and maintain normoglycemic
status. AIM AND OBJECTIVES: The aim of this study is to to evaluate antidiabetic
activity of AHPL/AYTAB/0513 tablet alone, oral hypoglycemic agents (OHA[s]), and
combination of AHPL/AYTAB/0513 tablet and OHA(s) in streptozotocin-induced
diabetes in rats. MATERIALS AND METHODS: Totally, ten groups of animals were
studied comparatively to evaluate antidiabetic activity of AHPL/AYTAB/0513
tablet, OHA(s), and combination of AHPL/AYTAB/0513 tablet and OHA(s). Blood
glucose level (BGL), lipid profile, serum creatinine, serum insulin level, and
histopathological characteristics of pancreas were studied to evaluate the
efficacy of various formulations. Histopathological examination of kidney and
heart was carried out to assess the ability of various formulations in preventing
complications of diabetes. RESULTS: There was a significant decrease in mean BGL,
serum triglycerides, serum total cholesterol, low-density lipoprotein (LDL), very
LDL, and serum creatinine levels in all formulations groups. Significant increase
in mean serum insulin level and high-density lipoprotein level was observed when
compared to diabetic control (DC) group. Recovery of pancreatic beta cells and
prevention of damage to heart and kidney cells was significant in all the
formulation groups as compared to DC group. None of the formulations tested in
nondiabetic rat showed hypoglycemia suggesting safety of all the formulations.
CONCLUSION: AHPL/AYTAB/0513 tablet alone and in combination with OHA(s) can be
effectively used in the management of diabetes mellitus. In addition,
AHPL/AYTAB/0513 tablet alone and in combination with OHA(s) help in prevention of
diabetic complications. As an adjuvant to OHA(s), AHPL/AYTAB/0513 tablet can be
more effective.
PMID- 28405577
TI - A comprehensive physicochemical, thermal, and spectroscopic characterization of
zinc (II) chloride using X-ray diffraction, particle size distribution,
differential scanning calorimetry, thermogravimetric analysis/differential
thermogravimetric analysis, ultraviolet-visible, and Fourier transform-infrared
spectroscopy.
AB - OBJECTIVE: Zinc chloride is an important inorganic compound used as a source of
zinc and has other numerous industrial applications. Unfortunately, it lacks
reliable and accurate physicochemical, thermal, and spectral characterization
information altogether. Hence, the authors tried to explore in-depth
characterization of zinc chloride using the modern analytical technique.
MATERIALS AND METHODS: The analysis of zinc chloride was performed using powder X
ray diffraction (PXRD), particle size distribution, differential scanning
calorimetry (DSC), thermogravimetric analysis/differential thermogravimetric
analysis (TGA/DTG), ultraviolet-visible spectroscopy (UV-vis), and Fourier
transform-infrared (FT-IR) analytical techniques. RESULTS: The PXRD patterns
showed well-defined, narrow, sharp, and the significant peaks. The crystallite
size was found in the range of 14.70-55.40 nm and showed average crystallite size
of 41.34 nm. The average particle size was found to be of 1.123 (d10), 3.025
(d50), and 6.712 (d90) MUm and average surface area of 2.71 m2/g. The span and
relative span values were 5.849 MUm and 1.93, respectively. The DSC thermogram
showed a small endothermic inflation at 308.10 degrees C with the latent heat
(DeltaH) of fusion 28.52 J/g. An exothermic reaction was observed at 449.32
degrees C with the DeltaH of decomposition 66.10 J/g. The TGA revealed two steps
of the thermal degradation and lost 8.207 and 89.72% of weight in the first and
second step of degradation, respectively. Similarly, the DTG analysis disclosed
Tmax at 508.21 degrees C. The UV-vis spectrum showed absorbance maxima at 197.60
nm (lambdamax), and FT-IR spectrum showed a peak at 511/cm might be due to the Zn
Cl stretching. CONCLUSIONS: These in-depth, comprehensive data would be very much
useful in all stages of nutraceuticals/pharmaceuticals formulation research and
development and other industrial applications.
PMID- 28405578
TI - The Chaperone TRAP1 As a Modulator of the Mitochondrial Adaptations in Cancer
Cells.
AB - Mitochondria can receive, integrate, and transmit a variety of signals to shape
many biochemical activities of the cell. In the process of tumor onset and
growth, mitochondria contribute to the capability of cells of escaping death
insults, handling changes in ROS levels, rewiring metabolism, and reprograming
gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic
needs of neoplastic cells in a rapid and flexible way, and these adaptations are
required for cell survival and proliferation in the fluctuating environment of a
rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial
adaptations are complex and only partially understood. Recently, the
mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor
associated protein 1) was identified as a key regulator of mitochondrial
bioenergetics in tumor cells, with a profound impact on neoplastic growth. In
this review, we analyze these findings and discuss the possibility that targeting
TRAP1 constitutes a new antitumor approach.
PMID- 28405580
TI - Temporomandibular joint reconstruction with alloplastic prosthesis: the outcomes
of four cases.
AB - BACKGROUND: The purpose of this study is to evaluate the outcomes of four
patients receiving stock Biomet TMJ prosthesis for reconstruction of the TMJs.
METHODS: TMJ reconstruction with stock Biomet TMJ prosthesis was performed in
four patients who had joint damages by trauma, tumor, resorption, and ankylosis,
which represent the indications of alloplastic prosthesis. RESULTS: Loss of
condyle from trauma and resorption of joint are good indications for prosthesis,
but the patients should be informed about limitation of jaw movement. In case of
structural damage of TMJ by tumor, tumor recurrence should be considered before
planning TMJ reconstruction. Considering heterotopic bone formation in case of
ankylosis, periodic follow-up and special surgical technique are required.
CONCLUSIONS: Given careful treatment planning and understanding the functional
limitation of TMJ prosthesis, alloplastic prosthesis is a safe and effective
management option for the reconstruction of TMJs.
PMID- 28405579
TI - A survey of methods and tools to detect recent and strong positive selection.
AB - Positive selection occurs when an allele is favored by natural selection. The
frequency of the favored allele increases in the population and due to genetic
hitchhiking the neighboring linked variation diminishes, creating so-called
selective sweeps. Detecting traces of positive selection in genomes is achieved
by searching for signatures introduced by selective sweeps, such as regions of
reduced variation, a specific shift of the site frequency spectrum, and
particular LD patterns in the region. A variety of methods and tools can be used
for detecting sweeps, ranging from simple implementations that compute summary
statistics such as Tajima's D, to more advanced statistical approaches that use
combinations of statistics, maximum likelihood, machine learning etc. In this
survey, we present and discuss summary statistics and software tools, and
classify them based on the selective sweep signature they detect, i.e., SFS-based
vs. LD-based, as well as their capacity to analyze whole genomes or just
subgenomic regions. Additionally, we summarize the results of comparisons among
four open-source software releases (SweeD, SweepFinder, SweepFinder2, and
OmegaPlus) regarding sensitivity, specificity, and execution times. In
equilibrium neutral models or mild bottlenecks, both SFS- and LD-based methods
are able to detect selective sweeps accurately. Methods and tools that rely on LD
exhibit higher true positive rates than SFS-based ones under the model of a
single sweep or recurrent hitchhiking. However, their false positive rate is
elevated when a misspecified demographic model is used to represent the null
hypothesis. When the correct (or similar to the correct) demographic model is
used instead, the false positive rates are considerably reduced. The accuracy of
detecting the true target of selection is decreased in bottleneck scenarios. In
terms of execution time, LD-based methods are typically faster than SFS-based
methods, due to the nature of required arithmetic.
PMID- 28405581
TI - Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem
cells.
AB - BACKGROUND: For an effective bone graft for reconstruction of the maxillofacial
region, an adequate vascular network will be required to supply blood,
osteoprogenitor cells, and growth factors. We previously reported that the
secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain
numerous growth factors such as insulin-like growth factor (IGF)-1, transforming
growth factor (TGF)-beta1, and vascular endothelial growth factor (VEGF), which
can affect the cellular characteristics and behavior of regenerating bone cells.
We hypothesized that angiogenesis is an important step for bone regeneration, and
VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic
potential. In the present study, we focused on VEGF in MSC-CM and evaluated the
angiogenic and osteogenic potentials of MSC-CM for bone regeneration. METHODS:
Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA).
Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC
CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube
formation was evaluated. For the evaluation of bone and blood vessel formation
with micro-computed tomography (micro-CT) and for the histological and
immunohistochemical analyses, a rat calvarial bone defect model was used.
RESULTS: The concentrations of IGF-1, VEGF, and TGF-beta1 in MSC-CM were 1515.6
+/- 211.8 pg/mL, 465.8 +/- 108.8 pg/mL, and 339.8 +/- 14.4 pg/mL, respectively.
Tube formation of HUVECs, bone formation, and blood vessel formation were
increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group.
Histological findings suggested that new bone formation in the entire defect was
observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF
group. Immunohistochemistry indicated that angiogenesis and migration of
endogenous stem cells were much more abundant in the MSC-CM group than in the MSC
CM + anti-VEGF group. CONCLUSIONS: VEGF is considered a crucial factor in MSC-CM,
and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration
with angiogenesis.
PMID- 28405583
TI - Corrigendum: Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene
Expression in Circulating Osteoclast Precursors.
AB - [This corrects the article on p. 5 in vol. 4, PMID: 28191455.].
PMID- 28405582
TI - Telehealth to Expand Community Health Nurse Education in Rural Guatemala: A Pilot
Feasibility and Acceptability Evaluation.
AB - Telehealth education has the potential to serve as an important, low-cost method
of expanding healthcare worker education and support, especially in rural
settings of low- and middle-income countries. We describe an innovative
educational strategy to strengthen a long-term health professional capacity
building partnership between Guatemalan and US-based partners. In this pilot
evaluation, community health nurses in rural Guatemala received customized,
interactive education via telehealth from faculty at the supporting US-based
institution. Program evaluation of this 10 lecture series demonstrated high
levels of satisfaction among learners and instructors as well as knowledge gain
by learners. An average of 5.5 learners and 2 instructors attended the 10
lectures and completed surveys using a Likert scale to rate statements regarding
lecture content, technology, and personal connection. Positive statements about
lecture content and the applicability to daily work had 98% or greater agreement
as did statements regarding ease of technology and convenience. The learners
agreed with feeling connected to the instructors 100% of the time, while
instructors had 86.4% agreement with connection related statements. Instructors,
joining at their respective work locations, rated convenience statements at 100%
agreement. This evaluation also demonstrated effectiveness with an average 10.7%
increase in pre- to posttest knowledge scores by learners. As the global health
community considers efficiency in time, money, and our environment, telehealth
education is a critical method to consider and develop for health worker
education. Our pilot program evaluation shows that telehealth may be an effective
method of delivering education to frontline health workers in rural Guatemala.
While larger studies are needed to quantify the duration and benefits of specific
knowledge gains and to perform a cost-effectiveness analysis of the program, our
initial pilot results are encouraging and show that a telehealth program between
a US-based university and a rural community health program in a low- and middle
income country is both feasible and acceptable.
PMID- 28405584
TI - Neogenin-YAP signaling in neocortical astrocytic differentiation.
AB - Astrocytes, a major type of glial cells in the mammalian central nervous system
(CNS), have a wide variety of physiological functions, including formation of the
blood brain barrier, and modulation of synaptic transmission and information
processing, and maintenance of CNS homeostasis. The signaling pathway initiated
by bone morphogenetic protein (BMP) is critical for astrogliogenesis. However,
exactly how this pathway regulates astrogliogenesis remains poorly understood. We
have recently provided in vitro and in vivo evidence for neogenin's function in
neural stem cells (NSCs) to promote neocortical astrogliogenesis. Neogenin in
NSCs as well as astrocytes is required for BMP2 activation of RhoA that promotes
YAP (yes-associated protein) nuclear translocation, consequently, YAP interaction
with nuclear p-Smad1/5/8, and stabilization of Smad1/5/8 signaling. We have also
provided evidence that YAP in NSCs is necessary for neocortical astrogliogenesis,
and expression of YAP in neogenin deficient NSCs diminishes the astrogliogenesis
deficit. These recent findings identify an unrecognized function of neogenin in
promoting neocortical astrogliogenesis, and reveal a pathway of BMP2-neogenin-YAP
Smad1 underlying astrogliogenesis in developing mouse neocortex.
PMID- 28405585
TI - A role for miR-19 in the migration of adult-born neurons and schizophrenia.
AB - The latest miRNA database (Release 21) annotated 2588 and 1915 miRNAs in the
human and mouse genomes, respectively.1 However, the biological roles of miRNAs
in vivo remain largely unknown. In particular, the physiological and pathological
roles of individual microRNAs in the brain have not been investigated extensively
although expression profiles of microRNAs have been reported in many given
conditions. In a recent study,2 we identified miR-19, which is enriched in adult
hippocampal neural progenitor cells (NPCs), as a key regulator for adult
hippocampal neurogenesis. miR-19 is an intrinsic factor regulating the migration
of newborn neurons by modulating expression level of RAPGEF2. After observing the
abnormal expression patterns of miR-19 and RAPGEF2 in NPCs derived from induced
pluripotent stem cells of schizophrenic patients, which display aberrant cell
migration, we proposed miR-19 as a molecule associated with schizophrenia. The
results illustrate that a single microRNA has the potential to impact the
functions of the brain. Identifying miRNA-mediated posttranscriptional gene
regulation in the brain will expand our understanding of brain development and
functions and the etiologies of several brain disorders.
PMID- 28405586
TI - Adult spinal cord neurogenesis: A regulator of nociception.
AB - Adult spinal cord neurogenesis occurs at low, constant rate under normal
conditions and can be amplified by pathologic conditions such as injury or
disease. The immature neurons produced through adult neurogenesis have increased
excitability and migrate preferentially to the superficial dorsal horn layers
responsible for nociceptive signaling. Under normal conditions, this process may
be responsible for maintaining a steady-state, but adaptable level of nociceptive
sensitivity, thus representing an experience-dependent mechanism of regulation
similar to other neurogenic niches. Under pathologic conditions, adult spinal
cord neurogenesis is greatly amplified and may therefore account for the observed
changes in general spinal cord excitability and nociceptive sensitivity. This
mechanism also explains many types of chronic pain present in the absence of
injury or disease, which may be the result of impaired neuronal differentiation
due to a variety of genetic variations. This suggests the possibility of using
promoters of neuronal differentiation for the long-term treatment of the causes
of chronic pain, unlike current medication which is palliative and effective only
for the duration of treatment. The presence of this spinal cord neurogenic niche
may also lead to new approaches in spinal cord regeneration.
PMID- 28405587
TI - A balancing Akt: How to fine-tune neuronal migration speed.
AB - In the developing mammalian neocortex, newborn neurons produced deep in the brain
from neural stem/progenitor cells set out for a long journey to reach their final
destination at the brain surface. This process called radial neuronal migration
is prerequisite for the formation of appropriate layers and networks in the
cortex, and its dysregulation has been implicated in cortical malformation and
neurological diseases. Considering a fine correlation between temporal order of
cortical neuronal cell types and their spatial distribution, migration speed
needs to be tightly controlled to achieve correct neocortical layering, although
the underlying molecular mechanisms remain not fully understood. Recently, we
discovered that the kinase Akt and its activator PDK1 regulate the migration
speed of mouse neocortical neurons through the cortical plate. We further found
that the PDK1-Akt pathway controls coordinated movement of the nucleus and the
centrosome during migration. Our data also suggested that control of neuronal
migration by the PDK1-Akt pathway is mediated at the level of microtubules,
possibly through regulation of the cytoplasmic dynein/dynactin complex. Our
findings thus identified a signaling pathway controlling neuronal migration speed
as well as a novel link between Akt signaling and cytoplasmic dynein/dynactin
complex.
PMID- 28405588
TI - Traceable microRNA-124 loaded nanoparticles as a new promising therapeutic tool
for Parkinson's disease.
AB - Parkinson's disease (PD), a neurodegenerative disorder characterized by the
selective degeneration of the nigrostriatal dopaminergic pathway, is a major
socio-economic burden in modern society. While there is presently no cure for PD,
enhancing the number of neural stem cells (NSCs) and/or stimulating their
differentiation into new neurons are promising therapeutic strategies. Many
proneurogenic factors have been implicated in controlling NSCs activity,
including the microRNA (miR)-124. However, current strategies described for the
intracellular delivery of miR involve mostly unspecific or inefficient platforms.
In Saraiva et al. we developed miR-124 loaded nanoparticles (NPs) able to
efficiently deliver miR-124 into neural stem/progenitor cells and boost neuronal
differentiation and maturation in vitro. In vivo, the intracerebroventricular
injection of miR-124 NPs increased the number of new neurons in the olfactory
bulb of healthy and 6-hydroxidopamine (6-OHDA) lesioned mice, a model for PD.
Importantly, miR-124 NPs enhanced the migration of new neurons into the 6-OHDA
lesioned striatum, culminating in motor function improvement. Given the recent
advent of clinical trials for miR-based therapies and the theranostic
applications of our NPs, we expect to support the clinical translation of our
delivery platform in the context of PD and other neurodegenerative diseases which
may benefit from enhancing miR levels.
PMID- 28405589
TI - The Arp2/3 complex is essential at multiple stages of neural development.
AB - During development of the nervous system, radial glial cells perform self
renewing asymmetric divisions and give rise to intermediate progenitor cells
(IPC) and neurons. The neuronally committed IPC subsequently undergo multiple
rounds of transient amplification and migrate outwards to form cortical layers as
they continue to differentiate into mature neurons. Maturing neurons extend
protrusions on their cell surface to form neurites, a process called
neuritogenesis. Neurite formation results in the establishment of dendrites and
axons for synapse formation, which is essential for sensory and motor functions
and even higher-level functioning including memory formation and cognitive
function, as well as shaping of behavior and emotion. Morphological adaptation
during various stages of neural development requires active participation of
actin cytoskeleton remodeling. In this review, we aim to discuss current
understanding of the Arp2/3 complex branching nucleator in various neural cell
types during development and maturation.
PMID- 28405590
TI - Therapeutic potential of IGF-I on hippocampal neurogenesis and function during
aging.
AB - In rats, learning and memory performance decline during normal aging, which is
paralleled by a severe reduction of the levels of neurogenesis in the hippocampal
dentate gyrus (DG). A promising therapeutic strategy to restore neurogenesis in
the hippocampus of old rats and their spatial memory involves the use of insulin
like growth factor-I (IGF-I). The peptide exerts pleiotropic effects in the
brain, regulating multiple cellular processes. Thus, 4-week
intracerebroventricular (ICV) perfusion of IGF-I significantly restored spatial
memory and hippocampal neurogenesis in old male rats. Similar results were
achieved by ICV IGF-I gene therapy in aging female rats. Thus, the treatment
seemed to increase the number of immature neurons in the DG of 28 mo old rats,
which was paralleled by an increase in the accuracy of the animals to remember
specific patterns, which is known as pattern separation memory. The DG is thought
to be the main hippocampal structure involved in pattern separation memory and
there is evidence that the level of neurogenesis in the DG is directly related to
pattern separation performance in rodents. Summing up, IGF-I emerges as a
promising restorative molecule for increasing hippocampal neurogenesis and memory
accuracy in aged individuals and possibly, in neurodegenerative pathologies.
PMID- 28405591
TI - SVD-aided pseudo principal-component analysis: A new method to speed up and
improve determination of the optimum kinetic model from time-resolved data.
AB - Determination of the optimum kinetic model is an essential prerequisite for
characterizing dynamics and mechanism of a reaction. Here, we propose a simple
method, termed as singular value decomposition-aided pseudo principal-component
analysis (SAPPA), to facilitate determination of the optimum kinetic model from
time-resolved data by bypassing any need to examine candidate kinetic models. We
demonstrate the wide applicability of SAPPA by examining three different sets of
experimental time-resolved data and show that SAPPA can efficiently determine the
optimum kinetic model. In addition, the results of SAPPA for both time-resolved X
ray solution scattering (TRXSS) and transient absorption (TA) data of the same
protein reveal that global structural changes of protein, which is probed by
TRXSS, may occur more slowly than local structural changes around the
chromophore, which is probed by TA spectroscopy.
PMID- 28405592
TI - Angle-resolved photoemission spectroscopy of liquid water at 29.5 eV.
AB - Angle-resolved photoemission spectroscopy of liquid water was performed using
extreme ultraviolet radiation at 29.5 eV and a time-of-flight photoelectron
spectrometer. SiC/Mg coated mirrors were employed to select the single-order 19th
harmonic from laser high harmonics, which provided a constant photon flux for
different laser polarizations. The instrument was tested by measuring
photoemission anisotropy for rare gases and water molecules and applied to a
microjet of an aqueous NaI solution. The solute concentration was adjusted to
eliminate an electric field gradient around the microjet. The observed
photoelectron spectra were analyzed considering contributions from liquid water,
water vapor, and an isotropic background. The anisotropy parameters of the
valence bands (1b1, 3a1, and 1b2) of liquid water are considerably smaller than
those of gaseous water, which is primarily attributed to electron scattering in
liquid water.
PMID- 28405593
TI - Molecular couplings and energy exchange between DNA and water mapped by
femtosecond infrared spectroscopy of backbone vibrations.
AB - Molecular couplings between DNA and water together with the accompanying
processes of energy exchange are mapped via the ultrafast response of DNA
backbone vibrations after OH stretch excitation of the water shell. Native salmon
testes DNA is studied in femtosecond pump-probe experiments under conditions of
full hydration and at a reduced hydration level with two water layers around the
double helix. Independent of their local hydration patterns, all backbone
vibrations in the frequency range from 940 to 1120 cm-1 display a quasi
instantaneous reshaping of the spectral envelopes of their fundamental absorption
bands upon excitation of the water shell. The subsequent reshaping kinetics
encompass a one-picosecond component, reflecting the formation of a hot ground
state of the water shell, and a slower contribution on a time scale of tens of
picoseconds. Such results are benchmarked by measurements with resonant
excitation of the backbone modes, resulting in distinctly different absorption
changes. We assign the fast changes of DNA absorption after OH stretch excitation
to structural changes in the water shell which couple to DNA through the local
electric fields. The second slower process is attributed to a flow of excess
energy from the water shell into DNA, establishing a common heated ground state
in the molecular ensemble. This interpretation is supported by theoretical
calculations of the electric fields exerted by the water shell at different
temperatures.
PMID- 28405594
TI - Screening for Novel Endogenous Inflammatory Stimuli Using the Secreted Embryonic
Alkaline Phosphatase NF-kappaB Reporter Assay.
AB - An immune response can be activated by pathogenic stimuli, as well as endogenous
danger signals, triggering the activation of pattern recognition receptors and
initiating signalling cascades that lead to inflammation. This method uses THP1
BlueTM cells, a human monocytic cell line which contains an embryonic alkaline
phosphatase reporter gene allowing the detection of NF-kappaB-induced
transcriptional activation. We validated this protocol by assessing NF-kappaB
activation after stimulation of toll-like receptor 4 (TLR4) by two different
agonists: lipopolysaccharide (LPS), derived from the cell wall of Gram negative
bacteria, and tenascin-C, an extracellular matrix protein whose expression is
induced upon tissue injury. We then used this protocol to screen for potential
new endogenous TLR4 agonists, but this method can also be used as a quick,
economical and reliable means to assay the activity of other inflammatory stimuli
resulting in TLR-dependent NF-kappaB activation.
PMID- 28405595
TI - In vivo Mitophagy Monitoring in Caenorhabditis elegans to Determine Mitochondrial
Homeostasis.
AB - Perturbation of mitochondrial function is a major hallmark of several
pathological conditions and ageing, underlining the essential role of fine-tuned
mitochondrial activity (Lopez-Otin et al., 2013). Mitochondrial selective
autophagy, known as mitophagy, mediates the removal of dysfunctional and/or
superfluous organelles, preserving cellular and organismal homeostasis (Palikaras
and Tavernarakis, 2014; Pickrell and Youle, 2015; Scheibye-Knudsen et al., 2015).
In this protocol, we describe a method for assessing mitophagy in the nematode
Caenorhabditis elegans.
PMID- 28405597
TI - "In-Site" Perfusion Technique for Rinse Solution in Liver Transplantation.
PMID- 28405596
TI - Associations Between Relative Value Units and Patient-Reported Back Pain and
Disability.
AB - Objective: To describe associations between health care utilization measures and
patient-reported outcomes (PROs). Method: Primary data were collected from
patients >=65 years with low back pain visits from 2011 to 2013. Six PROs of pain
and functionality were collected 12 and 24 months after the index visits and
total and spine-specific relative value units (RVUs) from electronic health
records were tabulated over 1 year. We calculated correlation coefficients
between RVUs and 12- and 24-month PROs and conducted linear regressions with each
12- and 24-month PRO as the outcome variables and RVUs as predictors of interest.
Results: We observed very weak correlations between worse PROs at 12 and 24
months and greater 12-month utilization. In regression analyses, we observed
slight associations between greater utilization and worse 12- and 24-month PROs.
Discussion: We found that 12-month health care utilization is not strongly
associated with PROs at 12 or 24 months.
PMID- 28405598
TI - Clearance of BK Virus Nephropathy by Combination Antiviral Therapy With
Intravenous Immunoglobulin.
AB - BACKGROUND: Reactivation of BK polyoma virus causes a destructive virus allograft
nephropathy (BKVAN) with graft loss in 46%. Treatment options are limited to
reduced immunosuppression and largely ineffective antiviral agents. Some studies
suggest benefit from intravenous immunoglobulin (IVIG). METHODS: We evaluated
effectiveness of adjuvant IVIG to eliminate virus from blood and tissue, in a
retrospective, single-center cohort study, against standard-of-care controls.
Both groups underwent reduced immunosuppression; conversion of tacrolimus to
cyclosporine; and mycophenolate to leflunomide, oral ciprofloxacin, and
intravenous cidofovir. RESULTS: Biopsy-proven BKVAN occurred in 50 kidneys at 7
(median interquartile range, 3-12) months after transplantation, predominantly as
histological stage B (92%), diagnosed following by dysfunction in 46%, screening
viremia in 20%, and protocol biopsy in 34%. After treatment, mean viral loads
fell from 1581 +/- 4220 * 103 copies at diagnosis to 1434 +/- 70 639
midtreatment, and 0.138 +/- 0.331 after 3 months (P < 0.001). IVIG at 1.01 +/-
0.18 g/kg was given to 22 (44%) patients. The IVIG group more effectively cleared
viremia (hazard ratio, 3.68; 95% confidence interval, 1.56-8.68; P = 0.003) and
BK immunohistochemistry from repeated tissue sampling (hazard ratio, 2.24; 95%
confidence interval, 1.09-4.58; P = 0.028), and resulted in faster (11.3 +/- 10.4
months vs 29.1 +/- 31.8 months, P = 0.015) and more complete resolution of
viremia (33.3% vs 77.3%, P = 0.044). Numerically, fewer graft losses occurred
with IVIG (27.3% vs 53.6% for control, P = 0.06), although graft and patient
survivals were not statistically different. Acute renal dysfunction requiring
pulse corticosteroid was common (59.1% vs 78.6%, P = 0.09), respectively, after
immunosuppression reduction. CONCLUSIONS: Combination treatment incorporating
adjuvant IVIG was more effective eliminating virus from BKVAN, compared with
conventional therapy. Validation by multicenter randomized trial is needed.
PMID- 28405599
TI - Absence of Intragraft B Cells in Rejection Biopsies After Rituximab Induction
Therapy: Consequences for Clinical Outcome.
AB - BACKGROUND: The pathophysiological role of intragraft B cells during renal
allograft rejection is unclear. METHODS: We studied B-cell infiltration during
acute rejection in 53 patients who participated in a clinical trial in which
adult renal transplant patients were randomized between a single intraoperative
dose of rituximab (375 mg/m2) or placebo as induction therapy. Two independent
pathologists scored all biopsies in a blinded fashion according to the Banff
classification and scored for the presence of B cells and plasma cells using
CD79a and CD138 as markers. RESULTS: The majority of acute rejections were T cell
mediated. The proportion of acute rejections with an antibody-mediated component
tended to be lower in rituximab-treated patients (4/23, 17.4%) than in placebo
treated patients (11/30, 36.7%; P = 0.14). Biopsies of rituximab-treated patients
had significantly lower scores for B cells (0.00; range, 0.00-0.50 vs 1.70;
range, 0.60-3.30; P < 0.0001) and plasma cells (0.10; range, 0.00-1.90 vs 0.40;
range, 0.00-7.50; P = 0.006). During acute rejection, intragraft clusters of B
cells were not observed after rituximab induction therapy. However, the depletion
of intragraft B cells during acute rejection did not affect steroid resistance,
proteinuria, graft function at 2 years follow-up, or patient and graft survival
at a median follow-up of 4.1 years (range, 2.0-6.2 years). CONCLUSIONS: These
data do not support a harmful influence of intragraft B cells present during
acute allograft rejection on the clinical course within the first few years after
renal transplantation.
PMID- 28405600
TI - Longitudinal Analysis of the Intestinal Microbiota in Liver Transplantation.
AB - BACKGROUND: Increasing evidence suggests that the intestinal microbiota plays an
important role in liver diseases. However, the dynamics of the intestinal
microbiota during liver transplantation (LT) and its potential role in clinical
course remain unknown. METHODS: We prospectively analyzed the intestinal
microbiota of 38 patients who underwent LT in Kyoto University Hospital. We
characterized the microbial compositions of fecal specimens from LT patients
using a metagenomics approach by an Illumina MiSeq platform. We analyzed the
diversity of microbiota sequentially from pretransplantation until 2 months after
LT and also compared the microbiota during an episode of acute cellular rejection
(ACR) and bloodstream infections (BSI) to the microbial composition of time
matched fecal specimens obtained from patients who did not experience ACR or BSI,
respectively. RESULTS: Three hundred twenty fecal specimens were analyzed.
Dynamic changes were observed in the microbial composition of LT recipients
during the perioperative period. Over the course of LT, the mean diversity index
decreased during the first 3 weeks after LT and gradually increased during our
observation period. The loss of intestinal microbiota diversity was associated
with high Child-Pugh scores, high model for end-stage liver disease scores, ACR,
and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae,
and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae,
Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR
patients. CONCLUSIONS: The microbiota of LT patients was associated with the
severity of liver diseases and the presence of ACR and BSI. These results lay the
groundwork for more comprehensive investigations of microbiota characteristics to
identify diagnostic markers for transplant health and to guide intervention
strategies to improve transplant outcomes.
PMID- 28405601
TI - Risk for Clostridium difficile Infection After Allogeneic Hematopoietic Cell
Transplant Remains Elevated in the Postengraftment Period.
AB - BACKGROUND: Clostridium difficile infection (CDI) is a frequent cause of diarrhea
among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown
whether risk factors for CDI vary by time posttransplant. METHODS: We performed a
3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants
were enrolled during their transplant hospitalizations. Clinical assessments were
performed weekly during hospitalizations and for 12 weeks posttransplant, and
monthly for 30 months thereafter. Data were collected through patient interviews
and chart review, and included CDI diagnosis, demographics, transplant
characteristics, medications, infections, and outcomes. CDI cases were included
if they occurred within 1 year of HCT and were stratified by time from
transplant. Multivariable logistic regression was used to determine risk factors
for CDI. RESULTS: One hundred eighty-seven allogeneic HCT recipients were
enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases
occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%)
postengraftment (day >30). Lack of any preexisting comorbid disease was
significantly associated with lower risk of CDI preengraftment (odds ratio [OR],
0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR,
6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95%
CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were
significant independent risk factors for CDI postengraftment. CONCLUSIONS: A
large portion of CDI cases occurred during the postengraftment period in
allogeneic HCT recipients, suggesting that surveillance for CDI should continue
beyond the transplant hospitalization and preengraftment period. Patients with
continued high underlying severity of illness were at increased risk of CDI
postengraftment.
PMID- 28405602
TI - Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor
Maintenance Therapy.
AB - BACKGROUND: Neurological disorders due to calcineurin inhibitor (CNI) treatment
pose a well-known problem after liver transplantation (LTx). In this study, the
impact of CNIs on cognitive functioning during maintenance therapy was analyzed.
A possible improvement of cognitive functioning, compliance and health-related
quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation
was prospectively assessed. METHODS: In a cross-section analysis cognitive
functioning of living donors (LD), waiting list patients and LTx patients was
tested using a 4 times trail making test (4-TTMT). In a further investigator
initiated trial a possible improvement of cognitive functioning, HRQoL and
compliance after conversion to the once-daily tacrolimus formulation was
prospectively assessed over 1 year. HRQoL was assessed using an EORTC-QLQ C30
questionnaire and patient's compliance was assessed by the Basel Assessment of
Compliance with Immunosuppressive Medication Scales questionnaire. Correlated
data were sex, age, time after surgery, liver disease, model of end-stage liver
disease score, creatinine, CNI type, and CNI trough levels. RESULTS: Two hundred
eleven patients were included in this cross-section analysis. Twenty-seven
patients agreed to participate in the investigator-initiated trial. LTx patients
completed the 4-TTMT slower than living donor patients and faster than waiting
list patients. Patients with twice daily cyclosporine A (CSA) formulation needed
longer to finish the 4-TTMT than patients with the once-daily tacrolimus
formulation. After drug conversion of a twice-daily CNI formulation to a once
daily tacrolimus formulation, CSA-treated patients needed longer to improve their
cognitive functioning. HRQoL and compliance did not improve after drug
conversion. CONCLUSIONS: Patients with once-daily tacrolimus formulation had a
better psychomotor speed than CSA-treated patients. The conversion to once-daily
tacrolimus formulation significantly improved cognitive functioning, but had no
impact on HRQoL or compliance.
PMID- 28405604
TI - The Authors' Reply.
PMID- 28405603
TI - mTOR Inhibition by Everolimus Does Not Impair Closure of Punch Biopsy Wounds in
Renal Transplant Patients.
AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to
prevent allograft rejection and control malignancy. Unfortunately, they are
associated with adverse effects, such as wound healing complications that detract
from more extensive use. There is a lack of prospective wound healing studies to
monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus,
especially in nondiabetics. METHODS: Patients receiving everolimus with standard
immunosuppressant therapy or standard immunosuppressant therapy without
everolimus were administered 3-mm skin biopsy punch wounds in the left scapular
region. Homeostatic gene expression was examined in the skin obtained from the
biopsy and wound surface area was examined on day 7. Peripheral blood mononuclear
cells were examined for cytokine production. RESULTS: There are no significant
changes in autophagy related 13, epidermal growth factor, insulin-like growth
factor binding protein 3, IL-2, kruppel-like factor 4, and TGFB1 gene expression
in the skin suggesting that there is little impact of everolimus on these genes
within nonwounded skin. Peripheral blood T cells are more sensitive to cell death
in everolimus-treated patients, but they retain the ability to produce
proinflammatory cytokines required for efficient wound repair. Importantly, there
is no delay in the closure of biopsy wounds in patients receiving everolimus as
compared to those not receiving mTOR inhibition. CONCLUSIONS: Everolimus
treatment is not associated with impaired closure of skin biopsy wounds in kidney
transplant recipients. These data highlight the importance of exploring whether
larger surgical wounds would show a similar result and how other factors, such as
diabetes, impact wound healing complications associated with mTOR suppression.
PMID- 28405605
TI - Three-Dimensional Self-Navigated T2 Mapping for the Detection of Acute Cellular
Rejection After Orthotopic Heart Transplantation.
AB - BACKGROUND: T2 mapping is a magnetic resonance imaging technique measuring T2
relaxation time, which increases with the myocardial tissue water content.
Myocardial edema is a component of acute cellular rejection (ACR) after heart
transplantation. This pilot study compares in heart transplantation recipients a
novel high resolution 3-dimensional (3D) T2-mapping technique with standard 2
dimensional (2D) T2-mapping for ACR detection. METHODS: Consecutive asymptomatic
patients (n = 26) underwent both 3D T2 mapping and reference 2D T2 mapping
magnetic resonance imaging on the day of endomyocardial biopsy (EMB). 3D T2 maps
were obtained at an isotropic spatial resolution of 1.72 mm (voxel volume 5.1
mm3). 2D and 3D maps were matched anatomically, and maximum segmental T2 values
were compared blinded to EMB results. In addition, all 3D T2 maps were rendered
as 3D images and inspected for foci of T2 elevation. RESULTS: T2 values of
segments from 2D and reformatted 3D T2 maps agreed (p > 0.5). The highest 2D
segmental T2 values were 49.9 +/- 4.0 ms (no ACR = 0R, n = 18), 48.9 +/- 0.8 ms
(mild ACR = 1R, n = 3), and 65.0 ms (moderate ACR = 2R). Rendered 3D T2 maps of
cases with 1R showed foci with significantly elevated T2 signal (T2 = 58.2 +/-
3.6 ms); 5 cases (28%) in the 0R group showed foci with increased T2 values (>2
SD above adjacent tissue) that were not visible on the 2D T2 maps. CONCLUSIONS:
This pilot study in a small cohort suggests equivalency of standard segmental
analysis between 3D and 2D T2-mapping. 3D T2 mapping provides a spatial
resolution that permits detection of foci with elevated T2 in patients with mild
ACR.
PMID- 28405606
TI - Changes in Markers of Mineral Metabolism After Living Kidney Donation.
AB - BACKGROUND: Living kidney donors (LKDs) experience reduction in kidney function,
however serum phosphate (sPi) levels are lower compared to patients with chronic
kidney disease matched for reduced kidney function. Mineral metabolism
adaptations that occur in LKDs have not been adequately investigated. To evaluate
the effect of nephrectomy on markers of mineral metabolism in LKDs compared to
healthy volunteers (HV) over 12 months. METHODS: Mineral parameters were
evaluated in twenty-one adult LKDs and twenty HVs. Parameters included sPi,
intact parathyroid hormone, fibroblast growth factor-23 (FGF23), soluble Klotho
(sKl) and urinary phosphate, measured prior to donation (T0), 1 month (T1), 6
months (T6) and 12 months (T12) post-kidney donation. Statistical analyses were
conducted on normalized variables and changes were assessed using 2-way analysis
of variance. RESULTS: Mean ages of LKDs and HVs were 54.1 +/- 14.7 and 52.6 +/-
8.0 years, respectively. There were no baseline clinical or biochemical
differences between LKDs and HVs. In LKDs at T1, serum creatinine increased (from
75 +/- 12 to 114 +/- 22 MUmol/L), FGF23 increased (52 +/- 15 to 70 +/- 19 pg/mL)
and sKl decreased (564 [469-662] to 424 [375-523] pg/mL), all P less than 0.001.
Changes were sustained at T12. After donation, LKDs consistently demonstrated
lower sPi compared with T0, with the maximal sPi change at T6 (-0.19 mmol/L
difference, P < 0.001). Other markers of mineral metabolism were unchanged in
LKDs. There were no mineral differences in HVs over 12 months. CONCLUSIONS:
Prospective evaluation of mineral metabolism parameters in LKDs provides valuable
insight into compensatory mechanisms after reduction in kidney function. Further
reduction of sPi at T6 despite early alterations in FGF23 and sKl suggest
adaptation of mineral metabolism continues long-term in LKDs.
PMID- 28405607
TI - Chemoattractant-mediated leukocyte trafficking enables HIV dissemination from the
genital mucosa.
AB - HIV vaginal transmission accounts for the majority of newly acquired heterosexual
infections. However, the mechanism by which HIV spreads from the initial site of
viral entry at the mucosal surface of the female genital tract to establish a
systemic infection of lymphoid and peripheral tissues is not known. Once the
virus exits the mucosa it rapidly spreads to all tissues, leading to CD4+ T cell
depletion and the establishment of a viral reservoir that cannot be eliminated
with current treatments. Understanding the molecular and cellular requirements
for viral dissemination from the genital tract is therefore of great importance,
as it could reveal new strategies to lengthen the window of opportunity to target
the virus at its entry site in the mucosa where it is the most vulnerable and
thus prevent systemic infection. Using HIV vaginal infection of humanized mice as
a model of heterosexual transmission, we demonstrate that blocking the ability of
leukocytes to respond to chemoattractants prevented HIV from leaving the female
genital tract. Furthermore, blocking lymphocyte egress from lymph nodes prevented
viremia and infection of the gut. Leukocyte trafficking therefore plays a major
role in viral dissemination, and targeting the chemoattractant molecules involved
can prevent the establishment of a systemic infection.
PMID- 28405608
TI - Circadian phase resetting by a single short-duration light exposure.
AB - BACKGROUND. In humans, a single light exposure of 12 minutes and multiple
millisecond light exposures can shift the phase of the circadian pacemaker. We
investigated the response of the human circadian pacemaker to a single 15-second
or 2-minute light pulse administered during the biological night. METHODS. Twenty
six healthy individuals participated in a 9-day inpatient protocol that included
assessment of dim light melatonin onset time (DLMO time) before and after
exposure to a single 15-second (n = 8) or 2-minute (n = 12) pulse of bright light
(9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux; n = 6).
Phase shifts were calculated as the difference in clock time between the two
phase estimates. RESULTS. Both 15-second and 2-minute exposures induced phase
delay shifts [median (+/- SD)] of -34.8 +/- 47.2 minutes and -45.4 +/- 28.4
minutes, respectively, that were significantly (P = 0.04) greater than the
control condition (advance shift: +22.3 +/- 51.3 minutes) but were not
significantly different from each other. Comparisons with historic data collected
under the same conditions confirmed a nonlinear relationship between exposure
duration and the magnitude of phase shift. CONCLUSIONS. Our results underscore
the exquisite sensitivity of the human pacemaker to even short-duration single
exposures to light. These findings may have real-world implications for circadian
disruption induced by exposure to brief light stimuli at night. TRIAL
REGISTRATION. The study was registered as a clinical trial on
www.clinicaltrials.org, NCT #01330992. FUNDING. Funding for this study was
provided by NSBRI HFP02802 and NIH P01-AG09975, R01-HL114088 (EBK), RC2-HL101340
0 (EBK, SWL, SAR, REK), K02-HD045459 (EBK), K24-HL105664 (EBK), T32-HL07901 (MSH,
SAR), HL094654 (CAC), and AG044416 (JFD). The project described was supported by
NIH grant 1UL1 TR001102-01, 8UL1TR000170-05, UL1 RR 025758, Harvard Clinical and
Translational Science Center, from the National Center for Advancing
Translational Science.
PMID- 28405609
TI - Preconditioned mesenchymal stem cells treat myasthenia gravis in a humanized
preclinical model.
AB - Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an
autoimmune disease characterized by severe defects in immune regulation and
thymic inflammation. Because mesenchymal stem cells (MSCs) display
immunomodulatory features, we investigated whether and how in vitro
preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new
humanized preclinical model by subcutaneously grafting thymic MG fragments into
immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed
human anti-AChR Abs in the serum, and 50% of the animals displayed MG-like
symptoms that correlated with the loss of AChR at the muscle endplates.
Interestingly, each mouse experiment recapitulated the MG features of each
patient. We next demonstrated that cMSCs markedly improved MG, reducing the level
of anti-AChR Abs in the serum and restoring AChR expression at the muscle
endplate. Resting MSCs had a smaller effect. Finally, we showed that the
underlying mechanisms involved (a) the inhibition of cell proliferation, (b) the
inhibition of B cell-related and costimulatory molecules, and (c) the activation
of the complement regulator DAF/CD55. In conclusion, this study shows that a
preconditioning step promotes the therapeutic effects of MSCs via combined
mechanisms, making cMSCs a promising strategy for treating MG and potentially
other autoimmune diseases.
PMID- 28405610
TI - Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell
associated damage in IFNalpha-driven lupus nephritis.
AB - Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell
activation promoting plasma cell generation, immune-complex deposition in the
kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I
IFNs amplify these autoimmune processes and promote severe disease. Bruton's
tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We
describe the characterization of a highly selective reversible Btk inhibitor, G
744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating
severe lupus nephritis in both spontaneous and IFNalpha-accelerated lupus in
NZB/W_F1 mice in therapeutic regimens. Selective Btk inhibition ablated
plasmablast generation, reduced autoantibodies, and - similar to cyclophosphamide
- improved renal pathology in IFNalpha-accelerated lupus. Employing global
transcriptional profiling of spleen and kidney coupled with cross-species human
modular repertoire analyses, we identify similarities in the inflammatory process
between mice and humans, and we demonstrate that G-744 reduced gene expression
signatures essential for splenic B cell terminal differentiation, particularly
the secretory pathway, as well as renal transcriptional profiles coupled with
myeloid cell-mediated pathology and glomerular plus tubulointerstitial disease in
human glomerulonephritis patients. These findings reveal the mechanism through
which a selective Btk inhibitor blocks murine autoimmune kidney disease,
highlighting pathway activity that may translate to human SLE.
PMID- 28405611
TI - Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's
disease.
AB - BACKGROUND. We report the 12-month clinical and imaging data on the effects of
bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic
nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD
patients were enrolled in a 6-month double-blind randomized trial of bilateral
AAV2-GAD delivery into the STN compared with sham surgery and were followed for
12 months in open-label fashion. Subjects were assessed with clinical outcome
measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements
under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores
in the AAV2-GAD group compared with the sham group continued at 12 months [time
effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03;
repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced
dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03;
post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all
FDG PET images over 12 months revealed significant metabolic declines (P < 0.001;
statistical parametric mapping RMANOVA) in the thalamus, striatum, and
prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group
compared with the sham group. Across all time points, changes in regional
metabolism differed for the two groups in all areas, with significant declines
only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore,
baseline metabolism in the prefrontal cortex (PFC) correlated with changes in
motor UPDRS scores; the higher the baseline PFC metabolism, the better the
clinical outcome. CONCLUSION. These findings show that clinical benefits after
gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL
REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.
PMID- 28405612
TI - MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair
antiviral response in COPD.
AB - Influenza A virus (IAV) infections lead to severe inflammation in the airways.
Patients with chronic obstructive pulmonary disease (COPD) characteristically
have exaggerated airway inflammation and are more susceptible to infections with
severe symptoms and increased mortality. The mechanisms that control inflammation
during IAV infection and the mechanisms of immune dysregulation in COPD are
unclear. We found that IAV infections lead to increased inflammatory and
antiviral responses in primary bronchial epithelial cells (pBECs) from healthy
nonsmoking and smoking subjects. In pBECs from COPD patients, infections resulted
in exaggerated inflammatory but deficient antiviral responses. A20 is an
important negative regulator of NF-kappaB-mediated inflammatory but not antiviral
responses, and A20 expression was reduced in COPD. IAV infection increased the
expression of miR-125a or -b, which directly reduced the expression of A20 and
mitochondrial antiviral signaling (MAVS), and caused exaggerated inflammation and
impaired antiviral responses. These events were replicated in vivo in a mouse
model of experimental COPD. Thus, miR-125a or -b and A20 may be targeted
therapeutically to inhibit excessive inflammatory responses and enhance antiviral
immunity in IAV infections and in COPD.
PMID- 28405613
TI - RIP140 in monocytes/macrophages regulates osteoclast differentiation and bone
homeostasis.
AB - Osteolytic bone diseases, such as osteoporosis, are characterized by diminished
bone quality and increased fracture risk. The therapeutic challenge remains to
maintain bone homeostasis with a balance between osteoclast-mediated resorption
and osteoblast-mediated formation. Osteoclasts are formed by the fusion of
monocyte/macrophage-derived precursors. Here we report, to our knowledge for the
first time, that receptor-interacting protein 140 (RIP140) expression in
osteoclast precursors and its protein regulation are crucial for osteoclast
differentiation, activity, and coupled bone formation. In mice,
monocyte/macrophage-specific knockdown of RIP140 (mphiRIP140KD) resulted in a
cancellous osteopenic phenotype with significantly increased bone resorption and
reduced bone formation. Osteoclast precursors isolated from mphiRIP140KD mice had
significantly increased differentiation potential. Furthermore, conditioned media
from mphiRIP140KD primary osteoclast cultures significantly suppressed osteoblast
differentiation. This suppressive activity was effectively and rapidly terminated
by specific Syk-stimulated RIP140 protein degradation. Mechanistic analysis
revealed that RIP140 functions primarily by inhibiting osteoclast differentiation
through forming a transcription-suppressor complex with testicular receptor 4
(TR4) to repress osteoclastogenic genes. These data reveal that
monocyte/macrophage RIP140/TR4 complexes may serve as a critical transcription
regulatory complex maintaining homeostasis of osteoclast differentiation,
activity, and coupling with osteoblast formation. Accordingly, we propose a
potentially novel therapeutic strategy, specifically targeting osteoclast
precursor RIP140 protein in osteolytic bone diseases.
PMID- 28405614
TI - IL-21 is required for CD4 memory formation in response to viral infection.
AB - IL-21 has been shown to play an important role in the CD8 T cell response during
acute and chronic viral infections. However, the role of IL-21 signaling in the
CD4 T cell response to viral infection remains incompletely defined. In a model
of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T
cells was critical for the formation of memory CD4 T cells in vivo. We further
reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on
activation of the STAT1 and STAT3 signaling pathways. In addition, the activation
of Akt is also required for IL-21-dependent survival of CD4 T cells in vivo.
These results identify a critical role for intrinsic IL-21 signaling in CD4 T
cell survival and memory formation in response to viral infection in vivo and may
provide insights into the design of effective vaccine strategies.
PMID- 28405615
TI - Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial
hypertrophy.
AB - IL-33 is one of the critical cytokines that activates group 2 innate lymphoid
cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests
that IL-33 is also involved in the pathogenesis of several chronic inflammatory
diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung
IL-5-producing ILC2s played essential roles in regulating eosinophil biology. In
this study, we evaluated the consequences of IL-33 administration over a long
period, and we observed significant expansion of ILC2s and eosinophils
surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe
occlusive hypertrophy that was ameliorated in IL-5- or eosinophil-deficient mice,
but not in Rag2-deficient mice. This indicates that IL-5-producing ILC2s and
eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration
of a clinically used vasodilator was effective in reducing IL-33-induced
hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together,
these observations demonstrate a previously unrecognized mechanism in the
development of pulmonary arterial hypertrophy and the causative roles of ILC2 in
the process.
PMID- 28405616
TI - The impact of environmental enrichment on the murine inflammatory immune
response.
AB - Living in a mentally and physically stimulating environment has been suggested to
have a beneficial effect on the immune response. This study investigates these
effects, utilizing a 2-week program of environmental enrichment (EE) and 2 models
of acute inflammation: zymosan-induced peritonitis (ZIP) and the cecal ligation
and puncture (CLP) model of sepsis. Our results revealed that following exposure
to EE, mice possessed a significantly higher circulating neutrophil to lymphocyte
ratio compared with control animals. When subject to ZIP, EE animals exhibit
enhanced neutrophil and macrophage influx into their peritoneal cavity.
Corresponding results were found in CLP, where we observed an improved capacity
for enriched animals to clear systemic microbial infection. Ex vivo investigation
of leukocyte activity also revealed that macrophages from EE mice presented an
enhanced phagocytic capacity. Supporting these findings, microarray analysis of
EE animals revealed the increased expression of immunomodulatory genes associated
with a heightened and immunoprotective status. Taken together, these results
provide potentially novel mechanisms by which EE influences the development and
dynamics of the immune response.
PMID- 28405617
TI - Inhibition of neuronal ferroptosis protects hemorrhagic brain.
AB - Intracerebral hemorrhage (ICH) causes high mortality and morbidity, but our
knowledge of post-ICH neuronal death and related mechanisms is limited. In this
study, we first demonstrated that ferroptosis, a newly identified form of cell
death, occurs in the collagenase-induced ICH model in mice. We found that
administration of ferrostatin-1, a specific inhibitor of ferroptosis, prevented
neuronal death and reduced iron deposition induced by hemoglobin in organotypic
hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after ICH
exhibited marked brain protection and improved neurologic function. Additionally,
we found that ferrostatin-1 reduced lipid reactive oxygen species production and
attenuated the increased expression level of PTGS2 and its gene product
cyclooxygenase-2 ex vivo and in vivo. Moreover, ferrostatin-1 in combination with
other inhibitors that target different forms of cell death prevented hemoglobin
induced cell death in OHSCs and human induced pluripotent stem cell-derived
neurons better than any inhibitor alone. These results indicate that ferroptosis
contributes to neuronal death after ICH, that administration of ferrostatin-1
protects hemorrhagic brain, and that cyclooxygenase-2 could be a biomarker of
ferroptosis. The insights gained from this study will advance our knowledge of
the post-ICH cell death cascade and be essential for future preclinical studies.
PMID- 28405618
TI - Efficacy of ALK5 inhibition in myelofibrosis.
AB - Myelofibrosis (MF) is a bone marrow disorder characterized by clonal
myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis,
and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have
been identified in the pathogenesis of these diseases, inhibitors of the Jak2
pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-beta
family members are profibrotic cytokines and we observed significant TGF-beta1
isoform overexpression in a large cohort of primary MF patient samples.
Significant overexpression of TGF-beta1 was also observed in murine clonal
MPLW515L megakaryocytic cells. TGF-beta1 stimulated the deposition of excessive
collagen by mesenchymal stromal cells (MSCs) by activating the TGF-beta receptor
I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated
sustained overproduction of both collagen I and collagen III, effects that were
abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of
galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in
both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of
malignant hematopoietic stem cell (HSC)/TGF-beta/MSC axis in the pathogenesis of
MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic
strategy in MF.
PMID- 28405619
TI - Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic
diabetes insipidus.
AB - Psychiatric patients treated with lithium (Li+) may develop nephrogenic diabetes
insipidus (NDI). Although the etiology of Li+-induced NDI (Li-NDI) is poorly
understood, it occurs partially due to reduced aquaporin-2 (AQP2) expression in
the kidney collecting ducts. A mechanism postulated for this is that Li+ inhibits
adenylyl cyclase (AC) activity, leading to decreased cAMP, reduced AQP2
abundance, and less membrane targeting. We hypothesized that Li-NDI would not
develop in mice lacking AC6. Whole-body AC6 knockout (AC6-/-) mice and
potentially novel connecting tubule/principal cell-specific AC6 knockout
(AC6loxloxCre) mice had approximately 50% lower urine osmolality and doubled
water intake under baseline conditions compared with controls. Dietary Li+
administration increased water intake and reduced urine osmolality in control,
AC6-/-, and AC6loxloxCre mice. Consistent with AC6-/- mice, medullary AQP2 and
pS256-AQP2 abundances were lower in AC6loxloxCre mice compared with controls
under standard conditions, and levels were further reduced after Li+
administration. AC6loxloxCre and control mice had a similar increase in the
numbers of proliferating cell nuclear antigen-positive cells in response to Li+.
However, AC6loxloxCre mice had a higher number of H+-ATPase B1 subunit-positive
cells under standard conditions and after Li+ administration. Collectively, AC6
has a minor role in Li-NDI development but may be important for determining the
intercalated cell-to-principal cell ratio.
PMID- 28405620
TI - Microglia mediate postoperative hippocampal inflammation and cognitive decline in
mice.
AB - Surgery can induce cognitive decline, a risk that increases with advancing age.
In rodents, postoperative cognitive decline (POCD) is associated with the
inflammatory activation of hippocampal microglia. To examine the role of
microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R)
in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial
fracture) reduced the ability of mice to remember a conditioned response learned
preoperatively, a deficit more pronounced and persistent in mice with diet
induced obesity (DIO). Whereas microglial depletion by itself did not affect
learning or memory, perioperative microglial depletion remarkably protected mice,
including those with DIO, from POCD. This protection was associated with reduced
hippocampal levels of inflammatory mediators, abrogation of hippocampal
recruitment of CCR2+ leukocytes, and higher levels of circulating inflammation
resolving factors. Targeting microglia may thus be a viable strategy to mitigate
the development of POCD, particularly in those with increased vulnerability.
PMID- 28405621
TI - LipidFinder: A computational workflow for discovery of lipids identifies
eicosanoid-phosphoinositides in platelets.
AB - Accurate and high-quality curation of lipidomic datasets generated from plasma,
cells, or tissues is becoming essential for cell biology investigations and
biomarker discovery for personalized medicine. However, a major challenge lies in
removing artifacts otherwise mistakenly interpreted as real lipids from large
mass spectrometry files (>60 K features), while retaining genuine ions in the
dataset. This requires powerful informatics tools; however, available workflows
have not been tailored specifically for lipidomics, particularly discovery
research. We designed LipidFinder, an open-source Python workflow. An algorithm
is included that optimizes analysis based on users' own data, and outputs are
screened against online databases and categorized into LIPID MAPS classes.
LipidFinder outperformed three widely used metabolomics packages using data from
human platelets. We show a family of three 12-hydroxyeicosatetraenoic acid
phosphoinositides (16:0/, 18:1/, 18:0/12-HETE-PI) generated by thrombin-activated
platelets, indicating crosstalk between eicosanoid and phosphoinositide pathways
in human cells. The software is available on GitHub
(https://github.com/cjbrasher/LipidFinder), with full userguides.
PMID- 28405622
TI - M1-like monocytes are a major immunological determinant of severity in previously
healthy adults with life-threatening influenza.
AB - In each influenza season, a distinct group of young, otherwise healthy
individuals with no risk factors succumbs to life-threatening infection. To
better understand the cause for this, we analyzed a broad range of immune
responses in blood from a unique cohort of patients, comprising previously
healthy individuals hospitalized with and without respiratory failure during one
influenza season, and infected with one specific influenza A strain. This
analysis was compared with similarly hospitalized influenza patients with known
risk factors (total of n = 60 patients recruited). We found a sustained increase
in a specific subset of proinflammatory monocytes, with high TNF-alpha expression
and an M1-like phenotype (independent of viral titers), in these previously
healthy patients with severe disease. The relationship between M1-like monocytes
and immunopathology was strengthened using murine models of influenza, in which
severe infection generated using different models (including the high
pathogenicity H5N1 strain) was also accompanied by high levels of circulating M1
like monocytes. Additionally, a raised M1/M2 macrophage ratio in the lungs was
observed. These studies identify a specific subtype of monocytes as a modifiable
immunological determinant of disease severity in this subgroup of severely ill,
previously healthy patients, offering potential novel therapeutic avenues.
PMID- 28405623
TI - BCG vaccination induces HIV target cell activation in HIV-exposed infants in a
randomized trial.
AB - BACKGROUND. Bacillus Calmette-Guerin (BCG) vaccine is administered at birth to
protect infants against tuberculosis throughout Africa, where most perinatal HIV
1 transmission occurs. We examined whether BCG vaccination alters the levels of
activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV
exposed infants were randomized to receive routine (at birth) or delayed (at 8
weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+ T
cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and
immune gene expression via PCR using Biomark (Fluidigm). RESULTS. Of 149 infants
randomized, 92% (n = 137) were retained at 6 weeks: 71 in the routine BCG arm and
66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in
systemic activation of HIV target CD4+CCR5+ T cells (HLA-DR+CD38+) at 6 weeks
(0.25% at birth versus 0.08% in delayed vaccination groups; P = 0.029), which
persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination
of the infants in the delayed arm at 8 weeks resulted in a similar increase in
activated CD4+CCR5+ T cells. The increase in activated T cells was associated
with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN
alpha1 transcripts within peripheral blood mononuclear cells but minimal changes
in innate cells. CONCLUSION. BCG vaccination induces immune changes in HIV
exposed infants, including an increase in the proportion of activated CCR5+CD4+
HIV target cells. These findings provide insight into optimal BCG vaccine timing
to minimize the risks of HIV transmissions to exposed infants while preserving
potential benefits conferred by BCG vaccination. TRIAL REGISTRATION.
ClinicalTrials.gov NCT02062580. FUNDING. This trial was sponsored by the
Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the
Thrasher Foundation (NR-0095); for details, see Acknowledgments.
PMID- 28405624
TI - GM-CSF is not essential for experimental autoimmune encephalomyelitis but
promotes brain-targeted disease.
AB - Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model
of multiple sclerosis to identify pathogenic cytokines that could be therapeutic
targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only
cytokine reported to be essential for EAE. We investigated the role of GM-CSF in
EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord
inflammation. Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully
susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF
during induction of spinal cord-targeted disease. In contrast, both GM-CSF and IL
17 were needed to fully overcome the inhibitory influence of IFN-gamma on the
induction of inflammation in the brain. Both GM-CSF and IL-17 independently
promoted neutrophil accumulation in the brain, which was essential for brain
targeted disease. These results identify a GM-CSF/IL-17/IFN-gamma axis that
regulates inflammation in the central nervous system and suggest that a
combination of cytokine-neutralizing therapies may be needed to dampen central
nervous system autoimmunity.
PMID- 28405625
TI - Resistance to hypertension mediated by intercalated cells of the collecting duct.
AB - The renal collecting duct (CD), as the terminal segment of the nephron, is
responsible for the final adjustments to the amount of sodium excreted in urine.
While angiotensin II modulates reabsorptive functions of the CD, the contribution
of these actions to physiological homeostasis is not clear. To examine this
question, we generated mice with cell-specific deletion of AT1A receptors from
the CD. Elimination of AT1A receptors from both principal and intercalated cells
(CDKO mice) had no effect on blood pressures at baseline or during successive
feeding of low- or high-salt diets. In contrast, the severity of hypertension
caused by chronic infusion of angiotensin II was paradoxically exaggerated in
CDKO mice compared with controls. In wild-type mice, angiotensin II induced
robust expression of cyclooxygenase-2 (COX-2) in renal medulla, primarily
localized to intercalated cells. Upregulation of COX-2 was diminished in CDKO
mice, resulting in reduced generation of vasodilator prostanoids. This impaired
expression of COX-2 has physiological consequences, since administration of a
specific COX-2 inhibitor to CDKO and control mice during angiotensin II infusion
equalized their blood pressures. Stimulation of COX-2 was also triggered by
exposure of isolated preparations of medullary CDs to angiotensin II. Deletion of
AT1A receptors from principal cells alone did not affect angiotensin II-dependent
COX2 stimulation, implicating intercalated cells as the main source of COX2 in
this setting. These findings suggest a novel paracrine role for the intercalated
cell to attenuate the severity of hypertension. Strategies for preserving or
augmenting this pathway may have value for improving the management of
hypertension.
PMID- 28405626
TI - Basic Scholarship in Biosafety Is Critically Needed To Reduce Risk of Laboratory
Accidents.
AB - Our firm conducted a risk/benefit assessment of "gain-of-function" research, as
part of the deliberative process following a U.S. moratorium on the research
(U.S. Department of Health and Human Services, U.S. Government Gain-of-Function
Deliberative Process and Research Funding Pause on Selected Gain-of-Function
Research Involving Influenza, MERS, and SARS Viruses, 2014). Due to significant
missing but theoretically acquirable data, our biosafety assessment faced
limitations, and we were forced to provide a relative, instead of absolute,
measure of risk (Gryphon Scientific, LLC, Risk and Benefit Analysis of Gain of
Function Research, 2016). Here, we argue that many of these types of missing data
represent large and stunning gaps in our knowledge of biosafety and argue that
these missing data, once acquired via primary research efforts, would improve
biosafety risk assessments and could be incorporated into biosafety practices to
reduce risk of accidents. Governments invest billions in biological research; at
least a small fraction of this support is warranted to prevent biological
accidents.
PMID- 28405627
TI - Bacterial Community Composition Associated with Pyrogenic Organic Matter
(Biochar) Varies with Pyrolysis Temperature and Colonization Environment.
AB - Microbes that colonize pyrogenic organic matter (PyOM) (also called biochar) play
an important role in PyOM mineralization and crucially affect soil biogeochemical
cycling, while the microbial community composition associated with PyOM particles
is poorly understood. We generated two manure-based PyOMs with different
characteristics (PyOM pyrolyzed at the low temperature of 300 degrees C [i.e.,
PyOM300] and at the high temperature of 700 degrees C [i.e., PyOM700]) and added
them to high-carbon (4.15%) and low-C (0.37%) soil for microbial colonization.
16S rRNA gene sequencing showed that Actinobacteria, particularly
Actinomycetales, was the dominant taxon in PyOM, regardless of the PyOM pyrolysis
temperature and soil type. Bacterial communities associated with PyOM particles
from high-C soils were similar to those in non-PyOM-amended soils. PyOM300 had
higher total microbial activity and more differential bacterial communities than
PyOM700. More bacterial operational taxonomic units (OTUs) preferentially thrived
on the low-pyrolysis-temperature PyOM, while some specific OTUs thrived on high
pyrolysis-temperature PyOM. In particular, Chloroflexi species tended to be more
prevalent in high-pyrolysis-temperature PyOM in low-C soils. In conclusion, the
differences in colonized bacterial community composition between the different
PyOMs were strongly influenced by the pyrolysis temperatures of PyOM, i.e., under
conditions of easily mineralizable C or fused aromatic C, and by other
properties, e.g., pH, surface area, and nutrient content. IMPORTANCE Pyrogenic
organic matter (PyOM) is widely distributed in soil and fluvial ecosystems and
plays an important role in biogeochemical cycling. Many studies have reported
changes in soil microbial communities stimulated by PyOM, but very little is
known about the microbial communities associated with PyOM. The microbes that
colonize PyOMs can participate in the mineralization of PyOM, so changing its
structure affects the fate of PyOMs and contributes to soil biogeochemical
cycling. This study identified the bacterial community composition associated
with PyOMs on the basis of high-throughput sequencing and demonstrated that both
PyOM pyrolysis temperature and the colonization environment determined the
bacterial community composition. Our work increases our understanding of the
dominant phylogenetic taxa associated with PyOMs, demonstrates mechanisms
mediating microbial metabolism and growth in PyOMs, and expands a new research
area for pyrogenic organic matter. This study identified the bacterial community
composition associated with PyOM, which is widely distributed in the environment.
Most bacterial OTUs preferentially thrived on PyOM pyrolyzed at low temperature,
while some specific OTUs thrived on PyOM pyrolyzed at high temperature.
PMID- 28405628
TI - Autism Link to Herpes Simplex Virus 2 Antibody in Pregnancy Likely To Be
Spurious.
PMID- 28405629
TI - Human Norovirus Evolution in a Chronically Infected Host.
AB - Typically, human noroviruses cause symptoms of acute gastroenteritis for 2 to 4
days. Often, the virions are shed in stool for several days after the symptoms
recede, which in turn can lead to further contamination and transmission.
Moreover, a number of reports have considered that chronic norovirus infections,
i.e., lasting months and years, might even function as reservoirs for the
generation of novel strains that can escape the herd immunity or have modified
binding interactions with histo-blood group antigens (HBGAs). In this study, we
analyzed noroviruses isolated from a patient who has presented a chronic
infection for more than 6 years. We found that the isolated capsid sequences
clustered into two main genetic types (termed A and B), despite a plethora of
capsid quasi-sequences. Furthermore, the two genetic types corresponded well with
distinct antigenicities. On the other hand, we showed that numerous amino acid
substitutions on the capsid surface of genetic types A and B did not alter the
HBGA binding profiles. However, divergent binding profiles for types A and B were
observed with human milk oligosaccharides (HMOs), which structurally mimic HBGAs
and may act as natural antivirals. Importantly, the isolated capsid sequences
only had approximately 90% amino acid identity with other known sequences, which
suggested that transmission of these chronic noroviruses could be limited.
IMPORTANCE The norovirus genogroup II genotype 4 (GII.4) variants have
approximately 5% divergence in capsid amino acid identity and have dominated over
the past decade. The precise reason(s) for the GII.4 emergence and persistence in
the human population is still unknown, but some studies have suggested that
chronically infected patients might generate novel variants that can cause new
epidemics. We examined GII.4 noroviruses isolated from an immunocompromised
patient with a long-term infection. Numerous norovirus capsid quasi-species were
isolated during the 13-month study. The capsid quasi-species clustered into two
genetic and antigenic types. However, the HBGA binding profiles were similar
between the two antigenic clusters, indicating that the amino acid substitutions
did not alter the HBGA binding interactions. The isolated sequences represented
two new GII.4 variants, but similar sequences were not found in the database.
These results indicated that chronically infected patients might not generate
novel noroviruses that cause outbreaks.
PMID- 28405630
TI - Efficient and Robust Paramyxoviridae Reverse Genetics Systems.
AB - The notoriously low efficiency of Paramyxoviridae reverse genetics systems has
posed a limiting barrier to the study of viruses in this family. Previous
approaches to reverse genetics have utilized a wide variety of techniques to
overcome the technical hurdles. Although robustness (i.e., the number of attempts
that result in successful rescue) has been improved in some systems with the use
of stable cell lines, the efficiency of rescue (i.e., the proportion of
transfected cells that yield at least one successful rescue event) has remained
low. We have substantially increased rescue efficiency for representative viruses
from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103
transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh
Rbz) sequence immediately preceding the start of the recombinant viral antigenome
and the use of a codon-optimized T7 polymerase (T7opt) gene to drive
paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high
efficiency rescue of paramyxovirus reverse genetics systems, featuring several
major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any
transfectable cell type for viral rescue, (iii) a single-step transfection
protocol, and (iv) use of the optimal T7 promoter sequence for high transcription
levels from the antigenomic plasmid without incorporation of nontemplated G
residues. The robustness of our T7opt-HhRbz system also allows for greater
latitude in the ratios of transfected accessory plasmids used that result in
successful rescue. Thus, our system may facilitate the rescue and interrogation
of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to
manipulate the genome of paramyxoviruses and evaluate the effects of these
changes at the phenotypic level is a powerful tool for the investigation of
specific aspects of the viral life cycle and viral pathogenesis. However, reverse
genetics systems for paramyxoviruses are notoriously inefficient, when
successful. The ability to efficiently and robustly rescue paramyxovirus reverse
genetics systems can be used to answer basic questions about the biology of
paramyxoviruses, as well as to facilitate the considerable translational efforts
being devoted to developing live attenuated paramyxovirus vaccine vectors.
PMID- 28405631
TI - Electric Cell-Substrate Impedance Sensing To Monitor Viral Growth and Study
Cellular Responses to Infection with Alphaherpesviruses in Real Time.
AB - Electric cell-substrate impedance sensing (ECIS) measures changes in an
electrical circuit formed in a culture dish. As cells grow over a gold electrode,
they block the flow of electricity and this is read as an increase in electrical
impedance in the circuit. ECIS has previously been used in a variety of
applications to study cell growth, migration, and behavior in response to stimuli
in real time and without the need for cellular labels. Here, we demonstrate that
ECIS is also a valuable tool with which to study infection by alphaherpesviruses.
To this end, we used ECIS to study the kinetics of cells infected with felid
herpesvirus type 1 (FHV-1), a close relative of the human alphaherpesviruses
herpes simplex virus 1 (HSV-1) and HSV-2, and compared the results to those
obtained with conventional infectivity assays. First, we demonstrated that ECIS
can easily distinguish between wells of cells infected with different amounts of
FHV-1 and provides information about the cellular response to infection. Second,
we found ECIS useful in identifying differences between the replication kinetics
of recombinant DsRed Express2-labeled FHV-1, created via CRISPR/Cas9 genome
engineering, and wild-type FHV-1. Finally, we demonstrated that ECIS can
accurately determine the half-maximal effective concentration of antivirals.
Collectively, our data show that ECIS, in conjunction with current methodologies,
is a powerful tool that can be used to monitor viral growth and study the
cellular response to alphaherpesvirus infection. IMPORTANCE Alphaherpesviruses,
including those that commonly infect humans, such as HSV-1 and HSV-2, typically
infect and cause cellular damage to epithelial cells at mucosal surfaces, leading
to disease. The development of novel technologies to study the cellular responses
to infection may allow a more complete understanding of virus replication and the
creation of novel antiviral therapies. This study demonstrates the use of ECIS to
study various aspects of herpesvirus biology, with a specific focus on changes in
cellular morphology as a result of infection. We conclude that ECIS represents a
valuable new tool with which to study alphaherpesvirus infections in real time
and in an objective and reproducible manner.
PMID- 28405632
TI - Evidence of Intercontinental Spread and Uncommon Variants of Low-Pathogenicity
Avian Influenza Viruses in Ducks Overwintering in Guatemala.
AB - Over a hundred species of aquatic birds overwinter in Central America's wetlands,
providing opportunities for the transmission of influenza A viruses (IAVs). To
date, limited IAV surveillance in Central America hinders our understanding of
the evolution and ecology of IAVs in migratory hosts within the Western
Hemisphere. To address this gap, we sequenced the genomes of 68 virus isolates
obtained from ducks overwintering along Guatemala's Pacific Coast during 2010 to
2013. High genetic diversity was observed, including 9 hemagglutinin (HA)
subtypes, 7 neuraminidase (NA) subtypes, and multiple avian IAV lineages that
have been detected at low levels (<1%) in North America. An unusually large
number of viruses with the rare H14 subtype were identified (n = 14) over two
consecutive seasons, the highest number of H14 viruses ever reported in a single
location, providing evidence for a possible H14 source population located outside
routinely sampled regions of North America. Viruses from Guatemala were
positioned within minor clades divergent from the main North American lineage on
phylogenies inferred for the H3, H4, N2, N8, PA, NP, and NS segments. A time
scaled phylogeny indicates that a Eurasian virus PA segment introduced into the
Americas in the early 2000s disseminated to Guatemala during ~2007.1 to 2010.4
(95% highest posterior density [HPD]). Overall, the diversity detected in
Guatemala in overwintering ducks highlights the potential role of Central America
in the evolution of diverse IAV lineages in the Americas, including divergent
variants rarely detected in the United States, and the importance of increasing
IAV surveillance throughout Central America. IMPORTANCE Recent outbreaks of
highly pathogenic H7N3, H5Nx, and H7N8 avian influenza viruses in North America
were introduced by migratory birds, underscoring the importance of understanding
how wild birds contribute to the dissemination and evolution of IAVs in nature.
At least four of the main IAV duck host species in North America migrate through
or overwinter within a narrow strip of Central America, providing opportunities
for diverse IAV lineages to mix and exchange gene segments. By obtaining whole
genome sequences of 68 IAV isolates collected from migratory waterfowl in
Guatemala (2010 to 2013), the largest data set available from Central America to
date, we detected extensive viral diversity, including gene variants rarely found
in North America and gene segments of Eurasian origin. Our findings highlight the
need for increased IAV surveillance across the geographical span of bird
migration flyways, including Neotropical regions that have been vastly
undersampled to date.
PMID- 28405633
TI - Genomic Analysis of Factors Associated with Low Prevalence of Antibiotic
Resistance in Extraintestinal Pathogenic Escherichia coli Sequence Type 95
Strains.
AB - Extraintestinal pathogenic Escherichia coli (ExPEC) strains belonging to
multilocus sequence type 95 (ST95) are globally distributed and a common cause of
infections in humans and domestic fowl. ST95 isolates generally show a lower
prevalence of acquired antimicrobial resistance than other pandemic ExPEC
lineages. We took a genomic approach to identify factors that may underlie
reduced resistance. We fully assembled genomes for four ST95 isolates
representing the four major fimH-based lineages within ST95 and also analyzed
draft-level genomes from another 82 ST95 isolates, largely from the western
United States. The fully assembled genomes of antibiotic-resistant isolates
carried resistance genes exclusively on large (>90-kb) IncFIB/IncFII plasmids.
These replicons were common in the draft genomes as well, particularly in
antibiotic-resistant isolates, but we also observed multiple instances of a
smaller (8.3-kb) ampicillin resistance plasmid that had been previously
identified in Salmonella enterica. Among ST95 isolates, pansusceptibility to
antibiotics was significantly associated with the fimH6 lineage and the presence
of homologs of the previously identified 114-kb IncFIB/IncFII plasmid pUTI89,
both of which were also associated with reduced carriage of other plasmids.
Potential mechanistic explanations for lineage- and plasmid-specific effects on
the prevalence of antibiotic resistance within the ST95 group are discussed.
IMPORTANCE Antibiotic resistance in bacterial pathogens is a major public health
concern. This work was motivated by the observation that only a small proportion
of ST95 isolates, a major pandemic lineage of extraintestinal pathogenic E. coli,
have acquired antibiotic resistance, in contrast to many other pandemic lineages.
Understanding bacterial genetic factors that may prevent acquisition of
resistance could contribute to the development of new biological, medical, or
public health strategies to reduce antibiotic-resistant infections.
PMID- 28405634
TI - Adolescents with idiopathic scoliosis and their parents have a positive attitude
towards the Thermobrace monitor: results from a survey.
AB - BACKGROUND: A temperature monitor is used to objectively measure brace wear time
in adolescent idiopathic scoliosis. The reliability of this device have been
demonstrated, and some specialists introduced the use of a compliance monitor as
a standard of care in everyday clinical practice, as we did since 2010 with the
Thermobrace (TB). The attitude towards these objective monitors has never been
investigated. The present study aims to investigate the attitude of parents and
patients towards the use of temperature sensors for measuring brace wear
compliance. METHODS: Three hundred one consecutive girls and 63 boys and their
parents have been interviewed. The inclusion criteria were as follows: brace wear
full-time prescription at first visit and at least one visit with download and
discussion of TB data. Usefulness, acceptability, reliability, and feeling
related to data download were the investigated domains. Patients were invited by
the administrative staff to complete anonymously the questionnaire. The European
Commission was informed about the present survey and approved it (ICT-37-2015-1).
Descriptive statistic was used to present the results. RESULTS: Among the 364
invited patients and parents, 336 adhered by completing it (rate of responders
was 93.2%). The mean age was 14.65 (SD 2.36), the mean Cobb angle was 34.18 (SD
13.57), and the average brace wear prescription was 21.76 h per day (SD 2.53). We
did not ask parents about their age, profession, nor other personal data.
Globally, the interviewed patients and parents showed a very positive attitude
towards the TB monitor: the mean rate of parents stating a completely or at least
partially positive attitude towards this electronic device was 94.0% while among
patients, it was 85.6%. CONCLUSIONS: This is the first study investigating the
attitude of parents and patients towards a brace wear compliance monitor. People
who experienced this objective monitoring are aware of the advantages related to
it and support its usefulness not only for clinicians but also for patients and
parents to respect the hours prescribed without any affection on the children and
parents or the patient-physician relationship. The present results should
encourage the spread of these tools in daily clinical practice.
PMID- 28405635
TI - Using Mendelian randomization to determine causal effects of maternal pregnancy
(intrauterine) exposures on offspring outcomes: Sources of bias and methods for
assessing them.
AB - Mendelian randomization (MR), the use of genetic variants as instrumental
variables (IVs) to test causal effects, is increasingly used in aetiological
epidemiology. Few of the methodological developments in MR have considered the
specific situation of using genetic IVs to test the causal effect of exposures in
pregnant women on postnatal offspring outcomes. In this paper, we describe
specific ways in which the IV assumptions might be violated when MR is used to
test such intrauterine effects. We highlight the importance of considering the
extent to which there is overlap between genetic variants in offspring that
influence their outcome with genetic variants used as IVs in their mothers. Where
there is overlap, and particularly if it generates a strong association of
maternal genetic IVs with offspring outcome via the offspring genotype, the
exclusion restriction assumption of IV analyses will be violated. We recommend a
set of analyses that ought to be considered when MR is used to address research
questions concerned with intrauterine effects on post-natal offspring outcomes,
and provide details of how these can be undertaken and interpreted. These
additional analyses include the use of genetic data from offspring and fathers,
examining associations using maternal non-transmitted alleles, and using
simulated data in sensitivity analyses (for which we provide code). We explore
the extent to which new methods that have been developed for exploring violation
of the exclusion restriction assumption in the two-sample setting (MR-Egger and
median based methods) might be used when exploring intrauterine effects in one
sample MR. We provide a list of recommendations that researchers should use when
applying MR to test the effects of intrauterine exposures on postnatal offspring
outcomes and use an illustrative example with real data to demonstrate how our
recommendations can be applied and subsequent results appropriately interpreted.
PMID- 28405636
TI - When transporters fail to be transported: how to rescue folding-deficient SLC6
transporters.
AB - The human dopamine transporter (hDAT) belongs to the solute carrier 6 (SLC6) gene
family. Point mutations in hDAT (SLC6A3) have been linked to a syndrome of
dopamine transporter deficiency or infantile dystonia/parkinsonism. The mutations
impair DAT folding, causing retention of variant DATs in the endoplasmic
reticulum and subsequently impair transport activity. The folding trajectory of
DAT itself is not understood, though many insights have been gained from studies
of folding-deficient mutants of the closely related serotonin transporter (SERT);
i.e. their functional rescue by pharmacochaperoning with (nor)ibogaine or heat
shock protein inhibitors. We recently provided a proof-of-principle that folding
deficits in DAT are amenable to rescue in vitro and in vivo. As a model we used
the Drosophila melanogaster DAT mutant dDAT-G108Q, which phenocopies the
fumin/sleepless DAT-knockout. Treatment with noribogaine and/or HSP70 inhibitor
pifithrin-MU restored folding of, and dopamine transport by, dDAT-G108Q, its
axonal delivery and normal sleep time in mutant flies. The possibility of
functional rescue of misfolded DATs in living flies by pharmacochaperoning grants
new therapeutic prospects in the remedy of folding diseases, not only in hDAT,
but also in other SLC6 transporters, in particular mutants of the creatine
transporter-1, which give rise to X-linked mental retardation.
PMID- 28405638
TI - A two-photon fluorescent probe for specific detection of hydrogen sulfide based
on a familiar ESIPT fluorophore bearing AIE characteristics.
AB - Hydrogen sulfide (H2S) is a signaling gasotransmitter, which plays various roles
in modulating the functions of different systems. In this study, a "turn-on"
fluorescent probe for H2S was developed. The probe, whose design is based on a
familiar excited state intramolecular proton transfer (ESIPT) fluorophore bearing
aggregation-induced emission (AIE) characteristics, was found to exhibit an 80
fold fluorescence enhancement along with a large Stokes shift upon the addition
of H2S. Furthermore, the probe was successfully utilized to detect H2S in HeLa
cells with both one-photon and two-photon microscopy.
PMID- 28405637
TI - Optimizing Interactive Development of Data-Intensive Applications.
AB - Modern Data-Intensive Scalable Computing (DISC) systems are designed to process
data through batch jobs that execute programs (e.g., queries) compiled from a
high-level language. These programs are often developed interactively by posing
ad-hoc queries over the base data until a desired result is generated. We observe
that there can be significant overlap in the structure of these queries used to
derive the final program. Yet, each successive execution of a slightly modified
query is performed anew, which can significantly increase the development cycle.
Vega is an Apache Spark framework that we have implemented for optimizing a
series of similar Spark programs, likely originating from a development or
exploratory data analysis session. Spark developers (e.g., data scientists) can
leverage Vega to significantly reduce the amount of time it takes to re-execute a
modified Spark program, reducing the overall time to market for their Big Data
applications.
PMID- 28405639
TI - A square-planar osmium(ii) complex.
AB - Reduction of the pincer complex [OsIIICl2(PNP)] (PNP = N(CHCHPtBu2)2) affords the
isolation and full characterization of an osmium(ii) complex with square-planar
coordination geometry, i.e. [OsIICl(PNP)]. Spectroscopic, structural and magnetic
data in combination with multireference computations indicate strong temperature
independent paramagnetism, which arises from an energetically well separated
ground state that mixes with excited states through spin-orbit coupling.
PMID- 28405641
TI - Light up detection of heparin based on aggregation-induced emission and
synergistic counter ion displacement.
AB - Heparin is a widely used anticoagulant and the quantification of heparin
concentration is pivotal for clinical use. However, previous fluorescent probes
for heparin detection are usually based on fluorophores with aggregation-caused
quenching (ACQ) properties, which severely restrict their applications for
quantitative measurement of heparin in a wide range. Herein, we develop an
aggregation-induced emission (AIE) probe HPQ-TBP-I for light up detection of
heparin based on the electrostatic interaction-triggered formation of the HPQ
TBP/heparin complex and simultaneous displacement of the fluorescence quencher
iodide ion. A linear relationship from 0 to 14 MUM of heparin accompanied with a
low detection limit of 22 nM was achieved, which fully covers the whole clinical
dose range (1.7-10 MUM). It is anticipated that this easily accessible and
sensitive AIE probe is promising for clinical applications.
PMID- 28405640
TI - Oxidative cyclization of 2-allenyl-1,1'-biphenyls with alpha-carbonyl alkyl
bromides: facile access to functionalized phenanthrenes.
AB - A new copper-facilitated oxidative cyclization of 2-allenyl-1,1'-biphenyls with
alpha-carbonyl alkyl bromides for producing functionalized phenanthrenes is
presented, which represents the first allene 2,3-dicarbofunctionalization
triggered by oxidative radical-medicated C3-addition of the terminal allene
moiety and C-Br/C-H functionalization.
PMID- 28405642
TI - Decoupling diffusion from the bimolecular photoinduced electron transfer
reaction: a combined ultrafast spectroscopic and kinetic analysis.
AB - We have studied the bimolecular photoinduced electron transfer (PET) reaction
between benzophenone (Bp) and DABCO using femtosecond broadband transient
absorption spectroscopy in different compositions of acetonitrile/1-butanol
binary solvent mixtures. With the increase in the 1-butanol percentage in the
mixture, we have observed an increase in the onset delay time of Bp-, which is
the product of the reaction. As 1-butanol is more viscous than acetonitrile, we
related the onset time to the change in medium viscosity. Moreover, we undertook
a complete kinetic analysis of the bimolecular PET reaction under different
conditions to show that from transient absorption spectroscopy, we can get the
exact rate of electron transfer. This kind of kinetic analysis along with the
experimental data is the first of its kind to prove that transient absorption
spectroscopy is probably the most useful tool in studying the PET reaction.
PMID- 28405643
TI - Cyclic ether synthesis from diols using trimethyl phosphate.
AB - Cyclic ethers have been effectively synthesized via the intramolecular
cyclization of diols using trimethyl phosphate and NaH. The present cyclization
could proceed at room temperature to produce 5-7 membered cyclic ethers in good
to excellent yields. Substrates possessing a chiral secondary hydroxy group were
transformed into the corresponding chiral cyclic ethers along with the retention
of their stereochemistries.
PMID- 28405644
TI - Alternative probe for the determination of the hydrogen-bond acidity of ionic
liquids and their aqueous solutions.
AB - Although highly relevant to a priori select adequate solvents for a given
application, the determination of the hydrogen-bond acidity or proton donor
ability of aqueous solutions of ionic liquids is a difficult task due to the poor
solubility of the commonly used probes in aqueous media. In this work, we
demonstrate the applicability of the pyridine-N-oxide probe to determine the
hydrogen-bond acidity of both neat ionic liquids and their aqueous solutions,
based on 13C NMR chemical shifts, and the suitability of these values to appraise
the ability of ionic liquids to form aqueous two-phase systems.
PMID- 28405645
TI - A new model of the chemistry of ionizing radiation in solids: CIRIS.
AB - The collisions between high-energy ions and solids can result in significant
physical and chemical changes to the material. These effects are potentially
important for better understanding the chemistry of interstellar and planetary
bodies, which are exposed to cosmic radiation and the solar wind, respectively;
however, modeling such collisions on a detailed microscopic basis has thus far
been largely unsuccessful. To that end, a new model, entitled CIRIS: the
Chemistry of Ionizing Radiation in Solids, was created to calculate the physical
and chemical effects of the irradiation of solid materials. With the new code, we
simulate O2 ice irradiated with 100 keV protons. Our models are able to reproduce
the measured ozone abundances of a previous experimental study, as well as
independently predict the approximate thickness of the ice used in that work.
PMID- 28405646
TI - Half-sandwich iridium N-heterocyclic carbene anticancer complexes.
AB - Half-sandwich pseudo-octahedral pentamethylcyclopentadienyl IrIII complexes of
the type [(eta5-Cpx)Ir(C^C)Cl]PF6, where Cpx is pentamethylcyclopentadienyl
(Cp*), or its phenyl (Cpxph = C5Me4C6H5) or biphenyl (Cpxbiph = C5Me4C6H4C6H5)
derivatives, and the C^C-chelating ligands are different N-heterocyclic carbene
(NHC) ligands, have been synthesized and characterized. Three X-ray crystal
structures have been determined. Except for Cp* complex 1A, the other eleven
complexes 1B-4C all showed potent cytotoxicity, with IC50 values ranging from 2.9
to 46.3 MUM toward HeLa human cervical cancer cells. The potency toward HeLa
cells increased with additional phenyl substitution on Cp*: Cpxbiph > Cpxph >
Cp*, and increased with the size of chain substitution on the C^C-ligand in the
order: ph > butyl > ethyl > methyl. Complex [(eta5-C5Me4C6H4C6H5)Ir(L4)Cl]PF6
(4C) displayed the highest potency, and was about 3 times more active than the
clinical platinum drug cisplatin. Complexes 1A-4C all undergo hydrolysis and
their kinetics was studied. DNA binding appears not to be the major mechanism of
action. The ability of these iridium complexes to catalyze hydride transfer from
the coenzyme NADH to NAD+ was studied. Complexes [(eta5
C5Me4C6H4C6H5)Ir(L2)Cl]PF6 (2C) and [(eta5-C5Me4C6H4C6H5)Ir(L3)Cl]PF6 (3C) cause
cell apoptosis and arrest the cell cycle at the G1 phase and G2/M phase when HeLa
cancer cells are treated with different IC50 concentrations of the complexes, and
increase the amount of reactive oxygen species (ROS) dramatically, which appears
to contribute to the anticancer activity. This class of organometallic Ir
complexes has unusual features worthy of further exploration in the design of
novel anticancer drugs.
PMID- 28405647
TI - Enzyme-induced dual-network epsilon-poly-l-lysine-based hydrogels with robust
self-healing and antibacterial performance.
AB - An enzyme-induced strategy is reported to construct novel self-mending hydrogels
based on epsilon-poly-l-lysine with both excellent self-healing properties (95%)
and antibacterial capacity. Most importantly, the hydrogels are able to
accelerate wound healing efficiently, which shows great potential in myriad
biomedical fields, such as wound repair, artificial skin, and tissue engineering.
PMID- 28405648
TI - Insight into the hydrogen evolution reaction of nickel dichalcogenide nanosheets:
activities related to non-metal ligands.
AB - Transition metal dichalcogenides, MX2 (M = Fe, Co, Ni, X = S, Se, Te), have been
proven to be promising substitutes for noble metals in hydrogen evolution
reactions (HERs). However, forthright comparisons of metal sulfides, metal
selenides, and metal tellurides are rarely conducted, let alone the mechanism of
the important role of their non-metal ligands. In this paper, we report the pilot
study of a controllable method for the preparation of a series of NiX2 (X = S,
Se, Te) nanosheets via a facile anion-exchange reaction. Consequently, the HER
activities and stabilities of NiS2, NiSe2, and NiTe2 nanosheets were tested in
both acid and alkaline solutions. The required overpotentials to reach 10 mA cm-2
in 0.5 M H2SO4 for NiS2, NiSe2, and NiTe2 were 213, 156, and 276 mV,
respectively. The best performance of NiSe2 was also confirmed in 1 M KOH.
Besides NiS2 and NiTe2 nanosheets, the HER properties of NiSe2 nanosheets are
superior to most of the available nickel catalysts. Interestingly, the results
from electrochemical measurements were found to be fully consistent with the data
based on density function theory calculation. Among various factors that might
influence the HER activities of nickel dichalcogenides, the free energies of
hydrogen adsorption and conductivities have played important roles.
PMID- 28405649
TI - A ligand design with a modified naphthyridylamide for achieving the longest
EMACs: the 1st single-molecule conductance of an undeca-nickel metal string.
AB - Striding to extend the length of metal-atom strings, oligo-alpha-pyridylamino
ligands are modulated with naphthyridyl moieties leading to the undeca-nickel
mixed-valence complexes [Ni11(bnatpya)4Cl2]4+ (1) and [Ni11(bnatpya)4Cl2]2+ (2).
The first single-molecule conductance measurements of a linear undeca-nickel
chain were performed.
PMID- 28405650
TI - Synthesis of fused cyanopyrroles and spirocyclopropanes via addition of N-ylides
to chalconimines.
AB - Addition of N-ylides derived from DABCO to chalconimines takes place through a
Michael addition-cyclization pathway to afford fused cyanopyrroles and/or
spirocyclopropanes. The product profile depends heavily on the nature of
chalconimines. While 6-membered cyclic chalconimines provide a mixture of pyrrole
and spirocyclopropane, 5-membered chalconimines furnish exclusively
spirocyclopropane. Cyclopropane was the only product in the case of a
representative open chain chalconimine as well. On the other hand, chalcones
provide only spirocyclopropanes which is in contrast to the previously reported
reactivity of enones. The complementary nature of the reactivity of the tetralone
derived chalcone and its corresponding imine in providing spirocyclopropane and
pyrrole, respectively, has also been demonstrated.
PMID- 28405651
TI - Structure and dynamics of [NH2(CH3)2]3Sb2Cl9 by means of 1H NMR relaxometry -
quadrupolar relaxation enhancement effects.
AB - 1H spin-lattice relaxation experiments have been performed for [NH2(CH3)2]3Sb2Cl9
(tris(dimethylammonium)nonachlorodiantimonate(iii)) in the temperature range of
253-313 K and a broad range of frequencies - from 4 kHz to 40 MHz. From the
analysis of quadrupolar relaxation enhancement effects (quadrupolar peaks)
associated with 14N nuclei, two lattice sites characterized by different electric
field gradient tensors have been revealed. The 14N quadrupolar couplings and
asymmetry parameters at these sites differ by a factor of about two. Three
motional processes have been identified and attributed to the overall dynamics of
the NH2(CH3)2 cations (slow motion), dynamics of the NH2 groups (intermediate
motion) and methyl group rotation (fast motion). It has been shown that the slow
dynamics is only weakly temperature dependent, while the intermediate and fast
motional processes are characterized by activation energies of 2.92 kJ mol-1 and
0.41 kJ mol-1, respectively. The correlation time of the slow dynamics is of the
order of MUs, while the intermediate dynamics is faster by 2-3 orders of
magnitude (depending on temperature). All correlation times have turned out to be
independent of the position of the cations in the lattice (they are the same for
both lattice sites). The analysis presented in this work is an example of the
potential of the quadrupolar relaxation enhancement effects as a method revealing
information on the dynamics and structure of solids.
PMID- 28405652
TI - Novel method for standard addition signal analysis in voltammetry.
AB - A new procedure for standard addition analysis in voltammetry based on the slope
of the peak at the inflection point (SSAA) is proposed. It is fully automated and
does not require any subjective user decisions. It has been tested for both
simulated and experimental data. Experimental data included DPASV measurements of
Pb(ii) and Cd(ii) on RAgABE, and Tl(i) on BiABE as a working electrode. In each
case the procedure offered good accuracy, precision and perfect reproducibility.
PMID- 28405653
TI - Organic-inorganic hybrid three-dimensional metal sulfite-oxalates with honeycomb
like structures.
AB - The crystallographic signatures and characterization of two novel mixed metal
hybrid open-frameworks [Na2Mn2(C2O4)(SO3)2(H2O)2] 1 and [NaEu(C2O4)(SO3)(H2O)3] 2
are reported for the first time; they are synthesized under hydrothermal
conditions to generate 3D assemblies and honeycomb-like structures. They were
further characterized by complementary techniques like PXRD, TGA and DSC. The
magnetic properties of 1 show antiferromagnetic interactions between the metal
centers and compound 2 shows good photoluminescence properties.
PMID- 28405654
TI - Direct observation of methoxycarbonylnitrene.
AB - The simplest alkoxycarbonylnitrene, CH3OC(O)N, has been generated through laser
(266 and 193 nm) photolysis of CH3OC(O)N3 and CH3OC(O)NCO and subsequently
characterized by IR (15N, D-labelling) and EPR (|D/hc| = 1.66 cm-1 and |E/hc| =
0.020 cm-1) spectroscopy in cryogenic matrices. Two conformers of the nitrene,
with the CH3 group being in syn or anti configuration to the C[double bond,
length as m-dash]O bond, have been unambiguously identified. Further UV light
irradiation (365 nm) of the nitrene results in isomerization to CH3ONCO,
completing the frequently explored mechanism for the Curtius-rearrangement of
CH3OC(O)N3.
PMID- 28405655
TI - Protocol for disentangling the thermally activated contribution to the tunneling
assisted charge transport. Analytical results and experimental relevance.
AB - In this paper we present results demonstrating that the charge transport by
tunneling in molecular junctions can exhibit a substantial temperature
dependence. We deduce an accurate analytical interpolation formula for the low
bias conductance G enabling disentangling into a temperature independent
contribution and a thermally activated contribution. The latter is found to have
a temperature dependence more general than the ubiquitous Arrhenius form, which
it recovers as a limiting case, and permits to extract the energy offset of the
molecular orbital that dominates the charge transport. Importantly, the
interpolation formula is general; it can be utilized for fitting experimental
conductance data for any form of transmission (e.g., Lorentzian, Gaussian,
generalized exponential or else). Furthermore, from the fitting parameters thus
obtained, valuable information on the energy dependence of the transmission
function can be gathered, which is hard to obtain from other methods. For
illustration, available experimental transport data at variable temperature for
molecular junctions are analyzed within the present theoretical framework. From a
more general perspective, the results reported here are important because they
attempt to give a constructive answer to the question of discriminating between
the (single-step) tunneling and (two-step) hopping mechanisms based on the
temperature dependence of the conductance. Namely, they suggest performing
variable temperature G-measurements on nanojunctions fabricated by contacting a
given molecular species to different electrodes and monitoring the metal
dependence of the activation energy.
PMID- 28405656
TI - A topologically unique alternating {CoGd} magnetocaloric ring.
AB - The adiabatic temperature change of the star-shaped {CoGd} magnetocaloric ring is
enhanced via topological control over the assembly process, by using a pre-formed
{CoII(H6L)} building block that undergoes oxidation to CoIII, successfully
separating the GdIII ions.
PMID- 28405657
TI - A triple-synergistic strategy for combinational photo/radiotherapy and multi
modality imaging based on hyaluronic acid-hybridized polyaniline-coated WS2
nanodots.
AB - In this study, we report a strategy for integrating hyaluronic acid (HA),
polyaniline (PANI), WS2 nanodots (WS2), and chlorin e6 (Ce6) into a single
nanoplatform (HA-WS2@PANI/Ce6) for fluorescence, photoacoustic, and computed
tomography multi-modality imaging-guided trimodal
photothermal/radiation/photodynamic combination therapy of tumors. The WS2
nanodot core is used as the radiosensitizer with the PANI shell as the
hyperthermal agent and the photosensitizer reservoir. HA and Ce6 were adsorbed on
the outer shell for tumor targeting and photodynamic therapy, respectively. The
in vivo trimodal imaging uncovered that HA-WS2@PANI/Ce6 nanoparticles showed
enhanced tumor uptake and diagnosis effects after intravenous injection. More
importantly, in the in vitro and in vivo experiments, the nanoparticles exhibited
an evident near-infrared induced photothermal effect, which remarkably improved
the radiation and photodynamic therapy efficiency by accelerating the blood flow
and subsequently increasing oxygen supply in the tumor. The nanohybrids were
found to be safe to cells in vitro and organs in vivo. Taken together, our
current work demonstrates a nanoplatform for multimodal imaging guided targeted
triple-therapy, which reveals a potential strategy for tumor treatment.
PMID- 28405658
TI - Surface passivation of mixed-halide perovskite CsPb(BrxI1-x)3 nanocrystals by
selective etching for improved stability.
AB - In recent years, there has been an unprecedented rise in the research of halide
perovskites because of their important optoelectronic applications, including
photovoltaic cells, light-emitting diodes, photodetectors and lasers. The most
pressing question concerns the stability of these materials. Here faster
degradation and PL quenching are observed at higher iodine content for mixed
halide perovskite CsPb(BrxI1-x)3 nanocrystals, and a simple yet effective method
is reported to significantly enhance their stability. After selective etching
with acetone, surface iodine is partially etched away to form a bromine-rich
surface passivation layer on mixed-halide perovskite nanocrystals. This
passivation layer remarkably stabilizes the nanocrystals, making their PL
intensity improved by almost three orders of magnitude. It is expected that a
similar passivation layer can also be applied to various other kinds of
perovskite materials with poor stability issues.
PMID- 28405659
TI - Recyclable Au-TiO2 nanocomposite SERS-active substrates contributed by
synergistic charge-transfer effect.
AB - In this study, Au deposited TiO2 (Au-TiO2) nanocomposites were prepared by
photocatalytic reduction of Au species (HAuCl4) on TiO2 nanoparticles (NPs) and
served as efficient SERS-active substrates. The observed considerable SERS
enhancement of 4-MBA molecules on Au-TiO2 NPs compared with that on pure TiO2 NPs
can be attributed to the synergistic contribution of semiconductors and metals by
the charge-transfer mechanism from the substrate to the molecule. In the
preparation of Au-TiO2 nanocomposites, the photo-reduction time and concentration
of HAuCl4 have an important influence on the SERS enhancement effect of the
composite substrate. Moreover, for the recycle of substrates, the photocatalytic
experiment of Au-TiO2 nanocomposites was carried out. The results show that these
nanocomposite substrates are characterized by a self-cleaning property and can be
repeatedly used in SERS experiments without losing their activity and with high
stability.
PMID- 28405660
TI - The role of the long-range tail of the potential in O2 + N2 collisional inelastic
vibrational energy transfers.
AB - In the study of non-reactive energy transfer between O2 and N2 molecules bearing
different vibrationally excited states we have faced the problem of selecting a
proper formulation of the interaction. To this end we have compared the values of
the related observables computed either on a potential energy surface globally
fitted to very large ab initio potential energy values [Varga et al., J. Chem.
Phys., 2016, 144, 024310] or on two more traditional ones formulated as a
combination of an intra- and inter-molecular model component of the interaction
(and based on a different combined use of experimental and ab initio information)
[Garcia et al., J. Phys. Chem. A, 2016, 120, 5208] in order to enforce an
appropriate modelling of the long-range tail of the potential, crucial for the
description of inelastic vibrational energy transfer. A detailed graphical
analysis of the potential plus a quantitative analysis of the computed opacity
functions, of the state-to-state rate coefficients, of the second virial
coefficient and of the integral non-reactive cross section allowed us to conclude
that the model formulation of the interaction has to be preferred for non
reactive studies of the O2 + N2 energy transfer processes in thermal and
subthermal regimes.
PMID- 28405661
TI - Small molecule induced poly(A) single strand to self-structure conformational
switching: evidence for the prominent role of H-bonding interactions.
AB - All messenger RNAs (mRNAs) have a polyadenylic acid tail that is added during
post transcriptional RNA processing. Investigation of the structure-function and
interactions of polyadenylic acid is an important area to target for cancer and
related diseases. Jatrorrhizine and coptisine are two important isoquinoline
alkaloids that are structurally very similar, differing only in the substituents
on the isoquinoline chromophore. Here we demonstrate that these alkaloids
differentially induce a self-structure in single stranded poly(A) using
absorbance, thermal melting and differential scanning calorimetry experiments.
Jatrorrhizine was found to be more effective than coptisine in binding to poly(A)
from spectroscopy and calorimetry data. Molecular modeling results suggested the
involvement of more H-bonds in the complexation of the former with poly(A). It
appears that the presence of substituents on the alkaloid that can form H-bonding
interactions with the adenine nucleotides may play a critical role in the binding
and structural rearrangement of poly(A) into the self-structure. The atomic force
microscopy data directly visualized the poly(A) self-structured network. We
propose a plausible mechanism of the small molecule induced self-structure
formation in poly(A). The results presented here may help in the design of
effective poly(A) targeted molecules for therapeutic use.
PMID- 28405662
TI - Assembly of hard spheres in a cylinder: a computational and experimental study.
AB - Hard spheres are an important benchmark of our understanding of natural and
synthetic systems. In this work, colloidal experiments and Monte Carlo
simulations examine the equilibrium and out-of-equilibrium assembly of hard
spheres of diameter sigma within cylinders of diameter sigma<=D<= 2.82sigma.
Although phase transitions formally do not exist in such systems, marked
structural crossovers can nonetheless be observed. Over this range of D, we find
in simulations that structural crossovers echo the structural changes in the
sequence of densest packings. We also observe that the out-of-equilibrium self
assembly depends on the compression rate. Slow compression approximates
equilibrium results, while fast compression can skip intermediate structures.
Crossovers for which no continuous line-slip exists are found to be dynamically
unfavorable, which is the main source of this difference. Results from colloidal
sedimentation experiments at low diffusion rate are found to be consistent with
the results of fast compressions, as long as appropriate boundary conditions are
used.
PMID- 28405663
TI - Enhancement of superconducting critical current density by Fe impurity
substitution in NbSe2 single crystals and the vortex pinning mechanism.
AB - Magnetization measurements have been used to determine the effect of magnetic
impurities (Fe) on the Larkin-Ovchinnikov (LO) 3D collective pinning model in
NbSe2 single crystals. Upon increasing the concentration of Fe impurities, the
superconducting critical current density enhances appreciably compared to pure
NbSe2 reflecting the fact that the addition of magnetic impurities assists in
improving the practical applicability of NbSe2. The random pinning potential that
is introduced by the Fe impurities also shows a considerable change in the
interaction between the vortices and the core region, resulting in a competitive
nature of single vortex, small bundle and large bundle pinning regimes in the H-T
phase diagram. The intrinsic disorder in pure NbSe2 single crystals shows deltaTc
flux pinning; however, the extrinsic disorder created by Fe atoms in NbSe2 shows
deltal flux pinning. Furthermore, the field dependence of the pinning force on
both NbSe2 and Fe-incorporated NbSe2 represents the existence of point pinning
and the surface pinning mechanism with a broadening of the fp curves in the Fe
incorporated single crystals.
PMID- 28405664
TI - Plasma assisted deposition of single and multistacked TiO2 hierarchical nanotube
photoanodes.
AB - We present herein an evolved methodology for the growth of nanocrystalline
hierarchical nanotubes combining physical vapor deposition of organic nanowires
(ONWs) and plasma enhanced chemical vacuum deposition of anatase TiO2 layers. The
ONWs act as vacuum removable 1D and 3D templates, with the whole process
occurring at temperatures ranging from RT to 250 degrees C. As a result, a high
density of hierarchical nanotubes with tunable diameter, length and tailored wall
microstructures are formed on a variety of processable substrates as metal and
metal oxide films or nanoparticles including transparent conductive oxides. The
reiteration of the process leads to the development of an unprecedented 3D
nanoarchitecture formed by stacking the layers of hierarchical TiO2 nanotubes. As
a proof of concept, we present the superior performance of the 3D
nanoarchitecture as a photoanode within an excitonic solar cell with efficiencies
as high as 4.69% for a nominal thickness of the anatase layer below 2.75 MUm.
Mechanical stability and straightforward implementation in devices are
demonstrated at the same time. The process is extendable to other functional
oxides fabricated by plasma-assisted methods with readily available applications
in energy harvesting and storage, catalysis and nanosensing.
PMID- 28405665
TI - Expanding the substrate scope of phenylalanine ammonia-lyase from Petroselinum
crispum towards styrylalanines.
AB - This study focuses on the expansion of the substrate scope of phenylalanine
ammonia-lyase from Petroselinum crispum (PcPAL) towards the l-enantiomers of
racemic styrylalanines rac-1a-d - which are less studied and synthetically
challenging unnatural amino acids - by reshaping the aromatic binding pocket of
the active site of PcPAL by point mutations. Ammonia elimination from l
styrylalanine (l-1a) catalyzed by non-mutated PcPAL (wt-PcPAL) took place with a
777-fold lower kcat/KM value than the deamination of the natural substrate, l
Phe. Computer modeling of the reactions catalyzed by wt-PcPAL indicated an
unproductive and two major catalytically active conformations and detrimental
interactions between the aromatic moiety of l-styrylalanine, l-1a, and the phenyl
ring of the residue F137 in the aromatic binding region of the active site.
Replacing the residue F137 by smaller hydrophobic residues resulted in a small
mutant library (F137X-PcPAL, X being V, A, and G), from which F137V-PcPAL could
transform l-styrylalanine with comparable activity to that of the wt-PcPAL with l
Phe. Furthermore, F137V-PcPAL showed superior catalytic efficiency in the ammonia
elimination reaction of several racemic styrylalanine derivatives (rac-1a-d)
providing access to d-1a-d by kinetic resolution, even though the d-enantiomers
proved to be reversible inhibitors. The enhanced catalytic efficiency of F137V
PcPAL towards racemic styrylalanines rac-1a-d could be rationalized by molecular
modeling, indicating the more relaxed enzyme-substrate complexes and the
promotion of conformations with higher catalytic activities as the main reasons.
Unfortunately, ammonia addition onto the corresponding styrylacrylates 2a-d
failed with both wt-PcPAL and F137V-PcPAL. The low equilibrium constant of the
ammonia addition, the poor ligand binding affinities of 2a-d, and the non
productive binding states of the unsaturated ligands 2a-d within the active sites
of either wt-PcPAL or F137V-PcPAL - as indicated by molecular modeling - might be
responsible for the inactivity of the PcPAL variants in the reverse reaction.
Modeling predicted that the F137V mutation is beneficial for the KRs of 4-fluoro
, 4-cyano- and 4-bromostyrylalanines, but non-effective for the KR process of 4
trifluoromethylstyrylalanine.
PMID- 28405666
TI - Self-assembled nitrogen-doped fullerenes and their catalysis for fuel cell and
rechargeable metal-air battery applications.
AB - In this study, we report self-assembled nitrogen-doped fullerenes (N-fullerene)
as non-precious catalysts, which are active for the oxygen reduction reaction
(ORR) and oxygen evolution reaction (OER), and thus applicable for energy
conversion and storage devices such as fuel cells and metal-air battery systems.
We screen the best N-fullerene catalyst at the nitrogen doping level of 10 at%,
not at the previously known doping level of 5 or 20 at% for graphene. We identify
that the compressive surface strain induced by doped nitrogen plays a key role in
the fine-tuning of catalytic activity.
PMID- 28405667
TI - Multiscale mechanics of the lateral pressure effect on enhancing the load
transfer between polymer coated CNTs.
AB - While individual carbon nanotubes (CNTs) are known as one of the strongest fibers
ever known, even the strongest fabricated macroscale CNT yarns and fibers are
still significantly weaker than individual nanotubes. The loss in mechanical
properties is mainly because the deformation mechanism of CNT fibers is highly
governed by the weak shear strength corresponding to sliding of nanotubes on each
other. Adding polymer coating to the bundles, and twisting the CNT yarns to
enhance the intertube interactions are both efficient methods to improve the
mechanical properties of macroscale yarns. Here, we perform molecular dynamics
(MD) simulations to unravel the unknown deformation mechanism in the intertube
polymer chains and also local deformations of the CNTs at the atomistic scale.
Our results show that the lateral pressure can have both beneficial and adverse
effects on shear strength of polymer coated CNTs, depending on the local
deformations at the atomistic scale. In this paper we also introduce a bottom-up
bridging strategy between a full atomistic model and a coarse-grained (CG) model.
Our trained CG model is capable of incorporating the atomistic scale local
deformations of each CNT to the larger scale collect behavior of bundles, which
enables the model to accurately predict the effect of lateral pressure on larger
CNT bundles and yarns. The developed multiscale CG model is implemented to study
the effect of lateral pressure on the shear strength of straight polymer coated
CNT yarns, and also the effect of twisting on the pull-out force of bundles in
spun CNT yarns.
PMID- 28405668
TI - Functional food supplements to ameliorate the secondary complications in high
fructose fed diabetic rats.
AB - Functional foods are the most natural and safest source of health ingredients,
providing health benefits beyond basic nutrition, and hence can be used as
supplements for the prevention of secondary complications in diabetes. Persistent
diabetes may cause glycation of various tissue proteins such as of those in lens,
kidney, blood, and brain, which may further lead to the development of
pathological conditions such as cataract and cardiovascular diseases. This study
on adult rats was designed to assess if the functional food supplements A and B
(proprietary blends of antioxidant rich plant materials) can reduce secondary
complications such as cataract, dyslipidemia, and oxidative stress under severe
diabetic conditions. After nine weeks of intervention of the supplements, it was
found that the % HbA1c levels in the formulation group B significantly (p < 0.05)
lowered (10.9%) followed by those in group A (11.1%) as compared to those in the
diabetic fructose control (DFC) group (15.1%); moreover, plasma insulin levels
were significantly (p < 0.01) improved in the formulation B group (9.8 mU L-1) as
compared to those in the DFC group (8.5 mU L-1). The significantly higher level
of plasma TEAC in group B (27.5 mg dL-1) (p < 0.02) and group A (26.6 mg dL-1) (p
< 0.05) indicates an improved plasma antioxidants status as compared to that in
DFC group (21.7 mg dL-1). Both the formulation groups A and B showed a decrease
in AGEs and tryptophan fluorescence, which suggests amelioration of the glycation
of lens proteins as compared to that in the DFC group. The present results
indicate that the formulations A and B exhibit antiglycating and antioxidant
potentials by inhibiting the high fructose-induced glycation in diabetic rats;
hence, they may have therapeutic value as functional foods in the effective
management of secondary complications associated with severe diabetic conditions.
PMID- 28405669
TI - Powdery polymer and carbon aerogels with high surface areas for high-performance
solid phase microextraction coatings.
AB - A novel powdery polymer aerogel (PPA) with a hierarchical pore structure was
prepared via hypercrosslinking of monodisperse poly(styrene-co-divinylbenzene)
nanoparticles. Subsequently, the PPA was carbonized to obtain a powdery carbon
aerogel (PCA) with a well-inherited pore structure and a much higher surface area
(2354 m2 g-1). The PPA-coated and PCA-coated fibers were easily fabricated
benefiting from the powdery morphologies of PPA and PCA, and demonstrated high
extraction efficiencies towards hydrophobic analytes owing to their functional
groups, unique three-dimensional (3D) porous nanonetworks and high surface areas.
PMID- 28405670
TI - A long-acting PAI-1 inhibitor reduces thrombus formation.
AB - Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type
and urokinase-type plasminogen activators (t/uPA) and plays an important role in
fibrinolysis. Inhibition of PAI-1 activity prevents thrombosis and accelerates
fibrinolysis, indicating that PAI-1 inhibitors may be used as effective
antithrombotic agents. We previously designed a PAI-1 inhibitor (PAItrap) which
is a variant of inactivated urokinase protease domain. In the present study, we
fused PAItrap with human serum albumin (HSA) to develop a long-acting PAI-1
inhibitor. Unfortunately, the fusion protein PAItrap-HSA lost some potency
compared to PAItrap (33 nM vs 10 nM). Guided by computational method, we carried
out further optimisation to enhance inhibitory potency for PAI-1. The new
PAItrap, denominated PAItrap(H37R)-HSA, which was the H37R variant of PAItrap
fused to HSA, gave a six-fold improvement of IC50 (5 nM) for human active PAI-1
compared to PAItrap-HSA, and showed much longer plasma half-life (200-fold)
compared to PAItrap. We further demonstrated that the PAItrap(H37R)-HSA inhibited
exogenous or endogenous PAI-1 to promote fibrinolysis in fibrin-clot lysis assay.
PAItrap(H37R)-HSA inhibits murine PAI-1 with IC50 value of 12 nM, allowing the
inhibitor to be evaluated in murine models. Using an intravital microscopy, we
demonstrated that PAItrap(H37R)-HSA blocks thrombus formation and platelet
accumulation in vivo in a laser-induced vascular injury mouse model.
Additionally, mouse tail bleeding assay showed that PAItrap(H37R)-HSA did not
affect the global haemostasis. These results suggest that PAItrap(H37R)-HSA have
the potential benefit to prevent thrombosis and accelerates fibrinolysis.
PMID- 28405671
TI - Predictors of oral cavity bleeding and clinical outcome after dental procedures
in patients on vitamin K antagonists. A cohort study.
AB - Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures.
International guidelines consider all dental procedures as low-risk procedures,
while bleeding risk may differ between standard low-risk (e. g. extraction 1-3
elements) and extensive high-risk (e. g. extraction of >3 elements) procedures.
Therefore current guidelines may need refinement. In this cohort study, we
identified predictors of oral cavity bleeding (OCB) and evaluated clinical
outcome after low-risk and high-risk dental procedures in patients on VKA.
Perioperative management strategy, procedure risk, and 30-day outcomes were
assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk
and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004
(3.3 %) low-risk and 21/325 (6.5 %) high-risk procedures (p=0.006). In low-risk
procedures, VKA continuation with tranexamic acid mouthwash was associated with a
lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23
0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24-1.00], and a similar
risk as interruption without bridging [OR=1.44, 95 %CI 0.62-3.64]. In high-risk
procedures, VKA continuation was associated with an increased OCB risk compared
to interruption [OR=3.08, 95 %CI 1.05-9.04]. Multivariate analyses revealed
bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR
before the procedure as strongest predictors of OCB. Non-oral cavity bleeding
(NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy
was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03
3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly
related to perioperative management and differed between low-risk and high-risk
procedures. Perioperative management should be differentiated accordingly.
PMID- 28405672
TI - Glucagon-like peptide 1-related peptides increase nitric oxide effects to reduce
platelet activation.
AB - Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only
its metabolic effects but also the protective vascular actions. Since platelets
exert a primary role in the pathogenesis of atherosclerosis, inflammation and
vascular complications, we investigated whether GLP-1 directly influences
platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we
evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute
incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP
1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation
induced by collagen or arachidonic acid (AA); ii) platelet function under shear
stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)
induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv)
activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt
and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress.
Experiments were repeated in the presence of the nitric oxide donor Na
nitroprusside. We found that platelets constitutively express GLP-1R and that,
independently of GLP-1R, GLP-1(7-36), GLP-1(9-36) and Liraglutide exert platelet
inhibitory effects as shown by: a) increased NO-antiaggregating effects, b)
increased the activation of the cGMP/PKG/VASP pathway, c) reduced the activation
of PI3-K/Akt and MAPK/ERK-2 pathways, d) reduced the AA-induced oxidative stress.
When the experiments were repeated in the presence of the antagonist of GLP-1R
Exendin(9-39), the platelet inhibitory effects were maintained, thus indicating a
mechanism independent of GLP-1R. In conclusion, GLP-1(7-36), its degradation
product GLP-1(9-36) and Liraglutide exert similar inhibitory effects on platelet
activation, suggesting a potential protective effect on the cardiovascular
system.
PMID- 28405674
TI - [New developments in molecularbiological diagnostic].
AB - Today, we have access to excellent and advanced molecular methods that are
already widely used. This requires rules to control the quality of the methods as
well as the laboratory. Both aspects will be discussed in the article. Following
the isolation of nucleic acids they are used for genotyping which allows to
address several questions: diagnosis of inherited diseases, inherited
predispositions, forensic analyses, identification and typing of bacteria or
viruses, elucidation of evolutionary aspects. Importantly, it has to be realized
that the type and heterogeneity of phenotypically relevant mutations determines
the method used for testing. Today, most laboratories use either PCR analyses or
Sanger sequencing for diagnostic applications. However, increasingly next
generation sequencing (NGS) is applied. The clinical use of NGS is still very
challenging, but we can expect that the switch to regular application of this
method will be coming in the very near future. The price for NGS has gone down to
approx. USD 1000,- which makes the routine diagnostic use feasible. Nevertheless,
several challenges have yet to be solved, such as the processing of the large
data volume as well as storage of the data. Supporting data bases exist already
and some will be discussed in the article. The understanding of the clinical
relevance of many polymorphisms is another issue that has yet to be solved,
particularly as in the context of personalized medicine polymorphisms have become
increasingly important.
PMID- 28405673
TI - Gly74Ser mutation in protein C causes thrombosis due to a defect in protein S
dependent anticoagulant function.
AB - Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon
activation by thrombin in complex with thrombomodulin (TM) down-regulates the
clotting cascade by a feedback loop inhibition mechanism. Activated protein C
(APC) exerts its anticoagulant function through protein S-dependent degradation
of factors Va and VIIIa. We recently identified a venous thrombosis patient whose
plasma level of protein C antigen is normal, but its anticoagulant activity is
only 34 % of the normal level. Genetic analysis revealed that the proband and her
younger brother carry a novel heterozygous mutation c.346G>A, p.Gly74Ser (G74S)
in PROC. Thrombin generation assay indicated that the TM-dependent anticoagulant
activity of the proband's plasma has been significantly impaired. We expressed
protein C-G74S in mammalian cells and characterised its properties in established
coagulation assays. We demonstrate that the protein C variant can be normally
activated by the thrombin-TM complex and the resulting APC mutant also exhibits
normal amidolytic and proteolytic activities toward both FVa and FVIIIa. However,
it was discovered the protein S-dependent catalytic activity of APC variant
toward both procoagulant cofactors has been significantly impaired. Protein S
concentration-dependence of FVa degradation revealed that the capacity of APC
variant to interact with the cofactor has been markedly impaired. The same
results were obtained for inactivation of FVa-Leiden suggesting that the protein
S-dependent activity of APC variant toward cleavage of Arg-306 site has been
adversely affected. These results provide insight into the mechanism through
which G74S substitution in APC causes thrombosis in the proband carrying this
mutation.
PMID- 28405675
TI - The management of acute venous thromboembolism in clinical practice. Results from
the European PREFER in VTE Registry.
AB - Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in
Europe. Data from real-world registries are necessary, as clinical trials do not
represent the full spectrum of VTE patients seen in clinical practice. We aimed
to document the epidemiology, management and outcomes of VTE using data from a
large, observational database. PREFER in VTE was an international, non
interventional disease registry conducted between January 2013 and July 2015 in
primary and secondary care across seven European countries. Consecutive patients
with acute VTE were documented and followed up over 12 months. PREFER in VTE
included 3,455 patients with a mean age of 60.8 +/- 17.0 years. Overall, 53.0 %
were male. The majority of patients were assessed in the hospital setting as
inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT)
in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities
were the various types of cardiovascular disease (excluding hypertension; 45.5
%), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a
large proportion of patients received initial therapy with heparin (73.2 %),
almost half received a vitamin K antagonist (48.7 %) and nearly a quarter
received a DOAC (24.5 %). Almost a quarter of all presentations were for
recurrent VTE, with >80 % of previous episodes having occurred more than 12
months prior to baseline. In conclusion, PREFER in VTE has provided contemporary
insights into VTE patients and their real-world management, including their
baseline characteristics, risk factors, disease history, symptoms and signs,
initial therapy and outcomes.
PMID- 28405676
TI - Ulinastatin protects against lipopolysaccharide-induced cardiac microvascular
endothelial cell dysfunction via downregulation of lncRNA MALAT1 and EZH2 in
sepsis.
AB - The present study aimed to evaluate the effects of ulinastatin on the
permeability and apoptosis of lipopolysaccharide (LPS)-induced cardiac
microvascular endothelial cells (CMVECs), and investigate its molecular
mechanisms in sepsis. The sepsis rat model was induced by cecal ligation and
puncture (CLP), and rat CMVECs were isolated and treated with LPS or/and
ulinastatin. Then, cell permeability was evaluated by transendothelial electrical
resistance, reactive oxygen species (ROS) levels were assessed by 2,7
dichlorofluorescein diacetate, cell apoptosis was detected using Annexin V-FITC
apoptosis detection kit, and the expression levels of Bcl-2, Bax, caspase-3,
metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and EZH2 were
detected by RT-qPCR and/or western blotting. In addition, the relationship of
MALAT1 and EZH2 was evaluated by RNA immunoprecipitation (RIP) assay and
chromatin immunoprecipitation (ChIP) assay. Compared with LPS-induced CMVECs,
treatment with ulinastatin significantly reduced CMVEC permeability and the
percentage of apoptotic cells, as well as an increased level of Bcl-2 and
inhibited the levels of ROS, caspase-3 and Bax (all p<0.05). In addition, long
non-coding RNA (lncRNA) MALAT1 was confirmed to interact with EZH2 in CMVECs.
Overexpression of lncRNA MALAT1 and EZH2 was found in the hearts of the sepsis
rat and LPS-induced CMVECs, while ulinastatin inhibited the upregulation of
lncRNA MALAT1 and EZH2 in the LPS-induced CMVECs (all p<0.05). Ulinastatin
protected against LPS-induced CMVEC cell hyperpermeability and apoptosis via
downregulation of lncRNA MALAT1 and EZH2 in sepsis.
PMID- 28405677
TI - Metastasized murine oral squamous cell carcinoma cells induce intratumoral
polymorphonuclear myeloid derived suppressor cells.
AB - Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and
peripheral blood during inflammation or tumor tissues and lymph nodes in the
presence of a tumor. However, whether there are differences in MDSCs found in the
primary tumor and metastases is unknown. In the present study, we established a
cell line of metastasized tumor cells to a lymph node, L5-11, which were derived
from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then
analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the
differences between the primary tumor and metastases, using an isogenic
heterotopic tumor transplantation model. Our data showed that the population of
intratumoral MDSCs, especially polymorphonuclear MDSCs in the lymph node
metastasis model were significantly increased compared with syngeneic grafts from
the primary cell line Sq-1979 after 21 days. Furthermore, we identified that the
lymph node metastasis cell line had increased expression of genes that promote
the expansion of MDSCs, tumor growth and metastasis. Hence, these data suggest
that tumor immunosuppression can occur via activation of MDSCs. However, further
examination is required to clarify whether all or a subset of these factors from
the lymph node metastasis tumor cells are required to induce intratumoral MDSCs.
PMID- 28405678
TI - CUTL1 induces epithelial-mesenchymal transition in non-small cell lung cancer.
AB - The homeobox transcription factor CUTL1 has been associated with cellular
proliferation and cell cycle progression, and CUTL1 functions as an oncogene. The
aim of the present study was to investigate whether CUTL1 participates in
epithelial-mesenchymal transition (EMT). The expression levels of CUTL1, E
cadherin, N-cadherin and Snail were determined by immunohistochemistry assay,
immunofluorescence assay or real-time quantitative reverse transcription PCR.
Their roles in non-small cell lung cancer (NSCLC) were assessed by functional
analyses. Protein expression was detected by western blot analysis. The CUTL1
expression levels are higher in non-small cell lung cancer (NSCLC) tissues. High
CUTL1 expression in NSCLC is associated with the mesenchymal-like phenotype.
Mechanistically, CUTL1 upregulates transforming growth factor beta receptor I
(TbetaR-I) expression, and the TbetaR-I inhibitor SB431542 abolishes EMT elicited
by ectopic CUTL1 expression. Transforming growth factor beta (TGF-beta) signaling
is essential for CUTL1-induced EMT in NSCLC cells. CUTL1 is downstream of TGF
beta signaling and CUTL1 is involved in the expression of the TbetaR-I. This
study indicates that CUTL1 may be a potential target for anti-lung cancer
therapy.
PMID- 28405679
TI - Hair keratin KRT81 is expressed in normal and breast cancer cells and contributes
to their invasiveness.
AB - Keratins are fibrous proteins. Hair keratins constitute hard structures such as
the hair and nails, and cytokeratins have been used as markers of breast
carcinoma. However, the expression and function of full-size hair keratin genes
have not been previously demonstrated in breast cancer. We investigated the
expression of the hair keratin, KRT81, and its function in human breast cancer
and normal mammary epithelial cells. Western blotting showed full size 55-kDa
KRT81 expression in the human breast cancer cell lines, MCF7, SKBR3 and MDA-MB
231, normal human mammary epithelial cells (HMEC), and non-neoplastic cells
(MCF10A). Reverse transcription-polymerase chain reaction revealed that the full
size KRT81, including its 5' region is expressed in breast cells.
Immunohistochemical and immunofluorescence analyses showed that KRT81 was located
in the cytoplasm. To investigate the function of KRT81, we knocked down KRT81 by
siRNA in MCF10A cells. Microarray analysis revealed that the expression of genes
related to invasion such as matrix metallopeptidase (MMP)9 was decreased. In
KRT81-knockdown MDA-MB231 cells, zymography revealed a decrease in MMP9 activity,
while scratch and invasion assays revealed that KRT81-knockdown decreased cell
migration and invasion abilities. This is the first study showing that full size
KRT81 is expressed in normal breast epithelial cells and breast cancer cells.
Moreover, our results indicate that KRT81 contributes to the migration and
invasion of breast cancer cells.
PMID- 28405680
TI - Optimal method for quantitative detection of plasma EGFR T790M mutation using
droplet digital PCR system.
AB - Though patients with EGFR mutations are initially responsive to EGFR-tyrosine
kinase inhibitors (TKIs), most tumors ultimately acquire resistance to EGFR-TKIs.
The most frequently reported mechanism is EGFR T790M mutation. In this study,
using a droplet digital PCR (ddPCR) system, we assessed optimal conditions for a
mutation detection assay for EGFR T790M obtained from circulating cell-free DNA
(cfDNA) in plasma. The advantages of locked nucleic acids (LNA) probe, short
amplicon size, and blocking oligo using peptide nucleic acids (PNA) were assessed
using control DNAs from cell lines to improve the sensitivity of mutation
detection. T790M alleles were then analyzed using ddPCR in 59 plasma samples from
24 NSCLC patients with EGFR mutations, and compared to the T790M status which
were determined thorough re-biopsies. The assessment of the optimal assay method
revealed that the assay using the short amplicon can efficiently detect more
fragmented-DNA. The LNA probe and PNA clamp contributed better separation between
positive and negative droplets. This PNA-LNA-ddPCR clamp method can detect mutant
alleles in the sample with a mutant allele content of 0.01%. In clinical plasma
samples, T790M alleles were detected via ddPCR with a sensitivity of 42.8% and
specificity of 97.3%. We established a highly-sensitive detection assay for the
T790M allele using the PNA-LNA-ddPCR clamp method. ddPCR is a promising method
for detecting non-invasive T790M mutation.
PMID- 28405681
TI - Maspin suppresses growth, proliferation and invasion in cutaneous squamous cell
carcinoma cells.
AB - Cutaneous squamous cell carcinoma (cSCC) is a common malignant tumor. Mammary
serine protease inhibitor (Maspin), a member of serpin family, has been reported
as a tumor suppressor in various carcinomas. In this study, we detected the
expression level of Maspin in cSCC tissues by real-time PCR and western blotting,
and found that Maspin was downregulated in the cSCC tissues compared with the
adjacent normal tissues. Moreover, Maspin was stably overexpressed in A431 cells,
and CCK-8 assay, colony formation assay, Transwell assay, Hoechst staining and
western blotting were carried out to detect the growth, proliferation, invasion,
cell cycle and apoptosis of A431 cells. The results revealed that overexpression
of Maspin inhibited growth, proliferation, invasion and cell cycle G1/S/G2
transition and enhanced apoptosis of A431 cells. The pro-apoptotic protein
cleaved caspase-3, poly(ADP-ribose) polymerase (PARP) and Bax increased, and the
anti-apoptotic protein Bcl-2 decreased after Maspin overexpression. Therefore, we
demonstrated that Maspin suppressed growth, proliferation and invasion by
delaying cell cycle transition and promoting apoptosis in cSCC cells, which may
provide new insights for the clinical diagnosis and therapy of cSCC.
PMID- 28405682
TI - Apamin suppresses biliary fibrosis and activation of hepatic stellate cells.
AB - Cholestatic liver disease is characterized by the progressive destruction of
biliary epithelial cells (BECs) followed by fibrosis, cirrhosis and liver
failure. Activated hepatic stellate cells (HSCs) and portal fibroblasts are the
major cellular effectors of enhanced collagen deposition in biliary fibrosis.
Apamin, an 18 amino acid peptide neurotoxin found in apitoxin (bee venom), is
known to block Ca2+-activated K+ channels and prevent carbon tetrachloride
induced liver fibrosis. In the present study, we aimed to ascertain whether
apamin inhibits biliary fibrosis and the proliferation of HSCs. Cholestatic liver
fibrosis was established in mouse models with 3,5-diethoxycarbonyl-1,4
dihydrocollidine (DDC) feeding. Cellular assays were performed on HSC-T6 cells
(rat immortalized HSCs). DDC feeding led to increased hepatic damage and
proinflammtory cytokine levels. Notably, apamin treatment resulted in decreased
liver injury and proinflammatory cytokine levels. Moreover, apamin suppressed the
deposition of collagen, proliferation of BECs and expression of fibrogenic genes
in the DDC-fed mice. In HSCs, apamin suppressed activation of HSCs by inhibiting
the Smad signaling pathway. These data suggest that apamin may be a potential
therapeutic target in cholestatic liver disease.
PMID- 28405683
TI - Bladder intracavitary hyperthermic perfusion chemotherapy for the prevention of
recurrence of non-muscle invasive bladder cancer after transurethral resection.
AB - Preventing the recurrence of non-muscle invasive bladder cancer (NMIBC) post
transurethral resection (TUR) remains challenging. The aim of the present study
was to investigate the effectiveness and safety of bladder intracavitary
hyperthermic perfusion chemotherapy (BHPC) for prevention of NMIBC recurrence
post-TUR. Between December 2006 and December 2014, 53 patients with NMIBC who
underwent TUR were randomly assigned to receive BHPC (BHPC group, 28 patients) or
intravesical chemotherapy alone (chemotherapy group, 25 patients) at the
Intracelom Hyperthermic Perfusion Therapy Center of Guangzhou Medical University
Cancer Hospital (Guangzhou, China). BHPC was performed by combining perfusion
based hyperthermia with chemotherapeutic agent mitomycin C (MMC) in the bladder,
and the chemotherapy group of patients received bladder MMC perfusion. The
concentration of MMC in the perfusion fluid and serum were assessed at different
time-points. Tumor recurrence, disease-free survival (DFS), and side-effects were
recorded and compared between the 2 groups. Results revealed that BHPC was
performed smoothly, at ~44C in the bladder cavity. Patients tolerated BHPC, and
no side-effects were observed. Both BHPC and intravesical chemotherapy achieved a
high MMC concentration in the bladder perfusion liquid, but low MMC concentration
in the serum, although serum MMC concentrations in the BHPC group were
significantly higher (P<0.05). The tumor recurrence rate was significantly lower
(10.7 vs. 28.0%; P=0.02) and the DFS period was significantly longer (37+/-1.2
vs. 19+/-0.9 months; P=0.001) in the BHPC group than in the chemotherapy group.
Our results demonstrated that BHPC is safe and effective for preventing NMIBC
recurrence post-TUR and prolongs DFS.
PMID- 28405684
TI - SphK1 modulates cell migration and EMT-related marker expression by regulating
the expression of p-FAK in colorectal cancer cells.
AB - Sphingosine kinase 1 (SphK1) plays an important role in colorectal carcinoma
metastasis. However, whether SphK1 modulates epithelial-mesenchymal transition
(EMT)-related marker expression and the underlying mechanisms remain unclear. In
this study, in order to clarify this issue, we used various colorectal cancer
(CRC) cell lines, Caco2, HT29, RKO and HCT116. Each of the cell lines was divided
into 3 groups as follows: the control group, SKI-II (SphK1 inhibitor) group and
PF-562271 [focal adhesion kinase (FAK) inhibitor] group. The migratory ability of
the cells was examined by Transwell chamber assay. The mRNA and protein
expression levels of SphK1, FAK (p-FAK), Slug, vimentin, N-cadherin and E
cadherin were detected by PCR and western blot analysis, respectively. The
results revealed that the suppression of SphK1 reduced the cell migratory
ability, and decreased the expression of Slug, vimentin and N-cadherin; however,
the expression of E-cadherin was increased. Moreover, the inhibition of SphK1
reduced the expression of p-FAK. The inhibition of FAK (p-FAK) also decreased the
cell migratory ability, and decreased the expression of Slug, vimentin and N
cadherin, whereas the expression of E-cadherin was increased. Thus, our data
suggest that SphK1 modulates the expression of EMT-related markers and cell
migration by regulating the expression of p-FAK in CRC cells. Thus, SphK1 may
play a functional role in mediating the EMT process in CRC.
PMID- 28405685
TI - siRNA-mediated inhibition of endogenous brain-derived neurotrophic factor gene
modulates the biological behavior of HeLa cells.
AB - Brain-derived neurotrophic factor (BDNF) is expressed in a number of neural and
non-neuronal tumors. The present study investigated the effect of endogenous BDNF
on the biological behavior of cervix cancer cells using small interfering RNA
(siRNA). HeLa, a cervix cancer cell line with high expression of BDNF, was used
as a living model to screen out the effective sequences of short hairpin RNA of
the BDNF gene, and the effects of RNA interference on proliferation, apoptosis,
migration and invasion of these cells were evaluated. Among the 4 siRNAs
examined, siRNA1 caused a 99% reduction in the relative BDNF mRNA level, while a
58% decrease in the relative BDNF protein level (p<0.01) was noted, and thus this
siRNA was selected as the most efficient for use in the present study. In
subsequent experiments, MTT assay revealed that BDNF silencing caused marked
inhibition of HeLa cell proliferation while Hoechst 33258 staining assay
demonstrated apoptosis-related changes in cell morphology. Downregulation of BDNF
expression induced cell cycle arrest in the G1 phase as shown by flow cytometry.
As indicated by Transwell migration and invasion assays, downregulation of BDNF
expression suppressed the migratory and invasive capabilities of the HeLa cells.
Together, our data revealed that BDNF modulates the proliferation, apoptosis,
migratory and invasive capabilities of HeLa cells. BDNF siRNA may represent a
novel therapy or drug target for preventing the tumorigenesis of cervical cancer.
PMID- 28405686
TI - Long non-coding RNA MEG3 induces cell apoptosis in esophageal cancer through
endoplasmic reticulum stress.
AB - Long non-coding RNAs (lncRNAs) play important roles in diverse biological
processes, such as cell growth, apoptosis and migration. Although downregulation
of lncRNA MEG3 has been identified in several cancers, little is known about its
role in esophageal squamous cell carcinoma (ESCC). The aim of the present study
was to detect MEG3 expression in clinical ESCC tissues, investigate its
biological functions and the endoplasmic reticulum (ER) stress-relative
mechanism. MEG3 expression levels were detected by qRT-PCR in both tumor tissues
and adjacent non-tumor tissues from 28 ESCC patients. PcDNA3.1-MEG3 recombinant
plasmids were constructed and transfected to EC109 cells. Cell growth was
analyzed by CCK-8 assay. Cell apoptosis was analyzed by fluorescence microscope
and Annexin V/PI assay. The protein expression was determined by western blot
analysis. The results showed that MEG3 decreased significantly in ESCC tissues
relative to adjacent normal tissues. PcDNA3.1-MEG3 plasmids were successfully
constructed and the expression level of MEG3 significantly increased after MEG3
transfection to EC109 cells. Ectopic expression of MEG3 inhibited EC109 cell
proliferation and induced apoptosis in vitro. MEG3 overexpression increased the
expression of ER stress-related proteins (GRP78, IRE1, PERK, ATF6, CHOP and
cleaved-caspase-3). Our results first demonstrate that MEG3 is downregulated in
ESCC tissues. MEG3 was able to inhibit cell growth and induced apoptosis in EC109
cells, most probably via activation of the ER stress pathway.
PMID- 28405688
TI - Regulation of glioma migration and invasion via modification of Rap2a activity by
the ubiquitin ligase Nedd4-1.
AB - Nueuronal precursor cell expressed and developmentally downregulated protein
(Nedd4-1) is an E3 ubiquitin ligase with critical roles in the pathogenesis of
cancer. Herein, we demonstrated that Nedd4-1 protein was upregulated in glioma
tissues vs. that in non-cancerous tissues by western blotting and
immunohistochemistry. Scratch migration and Transwell chamber assays indicated
that downregulation of Nedd4-1 significantly reduced the migration and invasion
of the glioma cell lines U251 and U87. Conversely, overexpression of Nedd4-1
obviously enhanced the migratory and invasive capacities in both cell lines. To
investigate the role of Nedd4-1 and the intracellular pathways involved, we
performed pull-down and co-immunoprecipitation assays, and recognized that Nedd4
1, TNIK and Rap2a formed a complex. Moreover, Nedd4-1 selectively ubiquitinated
its specific substrates, the wild-type Rap2a (WT-Rap2a) and dominant-active Rap2a
(DA-Rap2a) rather than the dominant-negative Rap2a (DN-Rap2a) in the U251 cells.
Subsequently, we demonstrated that Rap2a was robustly ubiquitinated by Nedd4-1
along with the K63-linked, but not the K48-linked ubiquitin chain, which
significantly inhibited GTP-Rap2a activity by GST-RalGDS pull-down assay. To
further verify whether the ubiquitination of Rap2a by Nedd4-1 regulated the
migration and invasion of glioma cells, Nedd4-1, HA-tagged ubiquitin and its
mutants as well as WT-Rap2a were co-transfected in the U251 and U87 cell lines.
The results confirmed that Nedd4-1 inhibited GTP-Rap2a activity, and promoted the
migration and invasion of glioma cells. In brief, our findings demonstrated the
important role of Nedd4-1 in regulating the migration and invasion of glioma
cells via the Nedd4-1/Rap2a pathway, which may qualify Nedd4-1 as a viable
therapeutic target for glioma.
PMID- 28405689
TI - Differential effects of sulforaphane in regulation of angiogenesis in a co
culture model of endothelial cells and pericytes.
AB - Aberrant neovascularization supports nutrients and the oxygen microenvironment in
tumour growth, invasion and metastasis. Recapitulation of functional
microvascular structures in vitro could provide a platform for the study of
vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to
possess chemopreventive properties. In the present study, the effects of SFN on
cell proliferation and tubular formation have been investigated using endothelial
cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on
the growth of ECs and pericytes with IC50 values 46.7 and 32.4 uM, respectively.
SFN (5-20 uM) inhibited tube formation in a 3D coculture although a lower dose
(1.25 uM) promoted 30% more endothelial tube formation than control. Moreover,
SFN affected intercellular communication between ECs and pericytes via inhibition
of angiogenic factor such as vascular endothelial growth factor (VEGF) expression
in pericytes. However, the expression of its receptor (VEGFR-2) was found
significantly increased in ECs. These effects were associated with downregulation
of prolyl hydroxylase domain-containing protein 1 and 2 (PHD1/2) and activation
of hypoxia-inducible factor-1 (HIF) pathway by SFN. Furthermore, thioredoxin
reductase-1 was also upregulated by SFN treatment, suggesting that anti-oxidant
and redox regulation are involved in angiogenesis. Taken together, the results of
the present study suggest that SFN differentially regulates endothelial cells and
pericytes disrupting their interplay through the VEGF-VEGFR signalling pathway.
Anti-angiogenesis property of SFN indicates that it has potential role as an
anticancer agent.
PMID- 28405687
TI - GINS2 is a novel prognostic biomarker and promotes tumor progression in early
stage cervical cancer.
AB - GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA
replication. GINS2 is upregulated in a variety of aggressive tumors. However, its
role in cervical cancer carcinogenesis remains to be elucidated. We investigated
the clinical significance of GINS2 in patients with early-stage cervical cancer
and its biological functions in cervical cancer progression. GINS2 expression was
analyzed in cervical cancer cell lines and in 8 matched cervical cancer samples
at the mRNA and protein levels using real-time PCR and western blotting,
respectively. GINS2 protein expression in 155 paraffin-embedded cervical cancer
specimens was validated using immunohistochemistry. Statistical analysis was used
to evaluate its clinicopathological significance. Short hairpin RNA interference,
anchorage-independent growth ability, colony formation assay, wound healing
ability, Transwell assays and western blotting were used to determine the effects
of GINS2 on the aggressive phenotype of cervical cancer cells. There was obvious
upregulation of GINS2 in the cervical cancer cell lines and tumor specimens
compared to that in the normal cervical tissues. Significant correlations were
identified between GINS2 expression and squamous cell carcinoma antigen (SCC-Ag;
P<0.001), deep stromal invasion (P=0.021), vital status (P<0.001), recurrence
(P<0.001) and pelvic lymph node metastasis (PLNM; P<0.001). Moreover, patients
with higher GINS2 expression had shorter overall survival (OS) compared to
patients with low GINS2 expression. Multivariate analysis revealed that GINS2 may
serve as an independent risk factor of poor prognosis in early-stage cervical
cancer. In addition, GINS2 downregulation markedly suppressed cell proliferation
and tumorigenic ability, as well as cell migration and invasion. Our findings
suggest that GINS2 is a novel indicator of PLNM and a valuable prognostic
biomarker in early-stage cervical cancer, and subsequently is a valuable
molecular target for cervical cancer diagnosis and treatment.
PMID- 28405690
TI - MicroRNA-30a-5p suppresses epithelial-mesenchymal transition by targeting
profilin-2 in high invasive non-small cell lung cancer cell lines.
AB - PFN2 is an invasion promoter in several cancers including lung cancer. However,
the probable effects and underlying mechanisms of PFN2 in tumor cell epithelial
mesenchymal-transition (EMT) of non-small cell lung cancer (NSCLC) remain poorly
understood. The protein and mRNA levels of PFN2 in human bronchial epithelial
cell line 16HBE and three NSCLC cell lines A549, NCI-H520 and 95D were assessed.
The gain-of-function (overexpression) and loss-of-function (siRNA) experiments of
PFN2 were performed in 95D cells. A dual-luciferase reporter assay, western
blotting and real-time PCR were used to investigate the relationship between PFN2
and miR-30a-5p. PFN2 was upregulated in three NSCLC cell lines, and the highest
in 95D cell line. Furthermore, the upregulation of PFN2 promoted, whereas the
downregulation of PFN2 suppressed invasion and EMT in 95D. Dual-luciferase
reporter assay showed that miR-30a-5p directly interacts with the 3'-untranslated
region (3'-UTR) of PFN2 mRNA. Interestingly, miR-30a-5p negatively regulates the
expression of PFN2 and suppresses EMT and invasion in 95D. In summary, the
present study demonstrated that miR-30a-5p inhibits EMT and invasion in high
invasive NSCLC cell lines via targeting PFN2. Suggesting the association of miR
30a-5p and PFN2 may play an essential role in the development of NSCLC by
modulating EMT and cell invasion.
PMID- 28405691
TI - [Customised early mobilisation : How about a little bit more?]
AB - Early mobilisation of patients in intensive care starts in a multiprofessional
team with passive techniques continuing with assistive measures and finally going
on to active training including mobilisation leading to sitting and standing
positions as well as walking. Positive effects regarding these procedures have
been proved in numerous studies and can also be found in the revision of the S2e
guideline "Positioning and early mobilisation in prophylaxis or therapy of
pulmonary disorders". In order to work with regard to the resources of the
patient in intensive care, of the multiprofessional team, of the ward-specific
structures and of the used equipment it is vital to apply a customised
mobilisation concept. Consequently, intensive care medicine is personalised which
means that the patient's needs are determined and precisely met. This and the
patient's present physical capacity lead to the adaptation of nursing and
therapeutic measures respectively. Some treatment methods and principles of
training theory can be applied to the intensive care patient if beforehand the
patient's current condition is evaluated by means of specific assessment methods.
As a result, appropriate forms of therapy and adequate stimuli of training can be
derived. The aim is a continuous process of early mobilisation with the best
possible outcome guaranteed by a closed system of evaluation and re-evaluation.
PMID- 28405692
TI - [Pulmonary carcinoid tumors].
AB - Pulmonary carcinoids are rare low-grade malignant tumors, which arise from the
neuroendocrine system. Approximately 80% of all pulmonary carcinoid tumors are
the relatively low-grade typical carcinoids and 20% are the more aggressive
atypical carcinoids. Most carcinoids arise from the central airways and only a
minority of carcinoids are found in the lung periphery. While most of the
peripheral carcinoids are asymptomatic, central carcinoids are symptomatic and
present with hemoptysis, wheezing or bronchial obstruction. On computed
tomography (CT), carcinoids frequently present as hypervascular pulmonary nodules
in close proximity to the bronchial system. Due to the bronchial obstruction,
many patients with pulmonary carcinoids present with post-obstructive pneumonia
or atelectasis. While fluorodeoxyglucose positron emission tomography CT (FDG
PET/CT) is of limited value in typical carcinoids due to the high rate of false
negatives, somatostatin analogs are promising tracers in staging as well as in
the planning of peptide receptor radionuclide therapy.
PMID- 28405693
TI - Monitoring Organophosphorous Pesticides Residues in the Shahid Rajaei Dam
Reservoir, Sari, Iran.
AB - Levels of eight different types of organophosphorous pesticides in water samples
from different parts of the Shahid Rajaei dam reservoir in north of Iran were
monitored. Water samples were collected from different locations of the reservoir
in June, July and September of 2015 and in February 2016. Water samples were
extracted with dichloromethane solvent and quantified using gas chromatography
and mass spectrometry analyses. The results showed that all pesticides were
detected for all periods and include dichlorvos, trifluralin, diazinon, methyl
parathion, fenitrothion, malathion, profenofos and ethion. The highest
concentrations were found in the summer that is related to malathion (on average
0.78 MUg L-1). In midwinter, no pesticide residues were detected. The results
showed that concentration of single and total pesticides for all stations were
greater than the maximum contamination level of the European Economic Commission.
PMID- 28405694
TI - Levels of Organotin Compounds in Selected Fish Species from the Arabian Gulf.
AB - In the present work, data on the levels of hazardous Organotin compounds in eight
commercially important fish species, caught from Arabian Gulf, has been reported.
Highest levels of tributyltin (TBT) (98.5 ng/g dry weight) were detected in
Epinephelus Tauvina whereas minimum (43.7 ng/g) were found in Acanthoparagus
Bifasciatus. Highest levels of triphenyltin (TPT) were detected in Lethrinus
Miniatus (107.5 ng/g) whereas lowest were encountered in Acanthoparagus
Bifasciatus (64.9 ng/g). Highest value of total butyltin compounds (?BT) were
found in emperors (Lethrinus Miniatus) (228.4 ng/g) whereas minimum was found in
Acanthoparagus Bifasciatus (126.4 ng/g). Similarly highest value of total
phenyltin compounds (?PT) was encountered in Epinephelus Tauvina (281.9 ng/g)
followed closely by Acanthoparagus Bifasciatus (281.7 ng/g). In addition, the
estimated daily intake (EDI) of the local population from consumption of these
fish was also evaluated. Highest EDI was found to be 10.8 ng/kg bw/day for
epinephelus microdan. The data are also compared internationally.
PMID- 28405695
TI - [The human microbiome].
PMID- 28405696
TI - [Varicella gastritis under immunosuppression : Case report of a woman after lung
transplantation due to granulomatosis with polyangiitis].
AB - A 35-year-old woman who had previously undergone a lung transplantation presented
with severe abdominal pain and vomiting. The gastroscopy showed diffuse
ulcerative gastric lesions. Tests for varicella zoster virus and Epstein-Barr
virus via polymerase chain reactions (PCR) on endoscopically obtained gastric
biopsies were found to be positive and confirmed varicella gastritis. Intravenous
antiviral therapy with acyclovir was administered resulting in a normalization of
all clinical symptoms, especially of abdominal pain and inflammation parameters.
PMID- 28405698
TI - The patent track sign.
PMID- 28405697
TI - Potentially inappropriate medicines in elderly hospitalised patients according to
the EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol.
AB - PURPOSE: The aim of this study was to measure the prevalence of potentially
inappropriate medications (PIMs) by using the EU(7)-PIM list, STOPP (Screening
Tool of Older Persons' potentially inappropriate Prescriptions) version 2
criteria and the new comprehensive protocol. METHODS: This prospective study
involved a sample of 276 consecutive elderly patients discharged from the
university teaching hospital. Age, gender, diagnoses, medication history and
medicines at discharge were recorded. The main outcome measure was the prevalence
of PIMs according to each set of criteria: EU(7)-PIM list, STOPP version 2
criteria and comprehensive protocol. RESULTS: The median patient age (range) was
74 (65-92) years. The median number of prescribed medications was 7 (1-17). STOPP
identified 393 PIMs affecting 190 patients (69%), EU(7)-PIM list identified 330
PIMs in 184 patients (66.7%) whilst the comprehensive protocol identified 134
PIMs in 102 patients (37%). STOPP version 2 criteria identified significantly
more PIMs per patient than the other two protocols (p < 0.001). Gender (p =
0.002), glomerular filtration rate (p = 0.039) and number of comorbidities (p =
0.001) were associated with the proportion of PIMs for the STOPP version 2
criteria only. CONCLUSION: A very high PIM prevalence at discharge was reported
suggesting the urgent need for actions to reduce them. STOPP version 2 criteria
identified significantly more PIMs than the EU(7)-PIM list and the comprehensive
protocol and was found as a more sensitive tool for PIM detection.
PMID- 28405699
TI - [Psychosocial care of refugees in Germany : Insights from the emergency relief
and development aid].
AB - Approximately 1.2 million refugees have arrived in Germany since autumn 2014.
They are often appraised as being a challenge for the German healthcare system
because the acute need for healthcare support was large and appeared suddenly
while at the same time resources were limited. This situation was previously
unknown for a western European healthcare system, whereas it constitutes a
typical challenge for nongovernmental organizations that are active in the field
of emergency relief and development aid and that have developed a large number of
successful intervention concepts. Of central importance in this context are the
basic principles of equal rights, participation of those affected, the principle
of nonmaleficence, the resource orientation instead of a deficit orientation as
well as the need for integrated and stepped care models. These can serve as
general principles not only in the setting of development aid in crisis areas
worldwide but also in the health services provided to refugees in the current
situation in Germany.
PMID- 28405700
TI - [Disorders of the will in psychopathology].
AB - At the beginning of modern psychopathology the notion of the will had a high
significance. Thus, the works of Eugen Bleuler, Emil Krapelin and Karl Jaspers
show an intensive study of disorders of the will, such as abulia, ambivalence or
disorders of impulse control. Retrospectively, changes of the scientific
paradigms in psychology could be one of the reasons for a break, which led to
giving up the concept of the will in psychopathology. With increasing interest in
issues of agency and free will, however, a reactivation of this central concept
could close a gap in psychopathology as well as in therapeutic practice.
Methodologically, a psychopathology of the will may be founded on a differential
typological phenomenology. To this purpose, the article first proposes a
classification along the structural components of conation, suspension and
volition, then gives a temporal analysis of the predecisional, the decisional and
the postdecisional phases. The aim of the article is to help identify different
disorders of the will, thus also furthering a psychotherapy of will, which can be
connected with both cognitive behavioral and psychodynamic approaches.
PMID- 28405701
TI - [Diabetes and the central nervous system].
AB - Diabetes increases the risk of stroke by a factor of 2-4. For primary and
secondary stroke prevention, strict glycemic control alone was not superior to
standard treatment. However, the risk of stroke in patients with diabetes could
be reduced by multimodal risk interventions during the last 20 years by about
50%. Increased glucose levels (poststroke hyperglycemia (PSH)) which indicate a
worse prognosis develop in 50% of stroke patients. The potentially beneficial
effect of strict glycemic control in PSH by i. v. insulin was neutralized by
negative effects of an increased rate of hypoglycemic episodes. Diabetes leads to
an increased risk of vascular dementia, but also of the neurodegenerative
Alzheimer 's type. Recurrent hypoglycemic episodes affect the timely perception
of hypoglycemia by cerebral-mediated mechanisms, which reduces the possibility of
counterreactions.
PMID- 28405702
TI - Erratum to: External validation of clinical decision rules for children with
wrist trauma.
PMID- 28405703
TI - Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a
murine model of nephrolithiasis.
AB - Metabolic syndrome (MS) individuals have a higher risk of developing chronic
kidney disease through unclear pathogenic mechanisms. MS has been also related
with higher nephrolithiasis prevalence. To establish the influence of MS on renal
function, we designed a murine model of combined metabolic syndrome and
hyperoxaluria. Four groups of male Sprague-Dawley rats were established: (1)
control group (n = 10) fed with standard chow; (2) stone former group (SF) (n =
10) fed with standard chow plus 0.75% ethylene glycol administered in the
drinking water; (3) metabolic syndrome group (MS) (n = 10), fed with 60% fructose
diet; (4) metabolic syndrome + stone former group (MS + SF) (n = 10), 60%
fructose diet and 0.75% EG in the drinking water. MS group showed a significant
injury to renal function when hyperoxaluria was induced. It was demonstrated by a
significant decrease of creatinine clearance (p < 0.001), with higher tubular
damage (34.3%, CI 95% 23.9-44.7, p < 0.001), produced by deposition of crystals,
and increased tubular synthesis of osteopontin as a response to tubular damage.
Induction of hyperoxaluria in rats with MS causes severe morphological
alterations with a significant impairment of renal function. This impairment is
not produced in rats without MS. Therefore, this model can be useful for the
study of the influence of MS in stone formation.
PMID- 28405705
TI - [Cost effectiveness of GnRH antagonists in patients with prostate cancer and
cardiovascular risk : Comparative analysis against Leuprorelin by the Number
Needed to Treat].
AB - BACKGROUND: Recent studies suggest that androgen deprivation therapy (ADT) is
associated with increased cardiovascular (CV) risk for patients with hormone
sensitive prostate cancer (PCa) and pre-existing CV disease. This risk seems to
be different for the gonadotropin-releasing hormone (GnRH) agonists leuprolide
and goserelin and GnRH antagonists, whereas the slightly more expensive GnRH
antagonist shows a beneficial risk profile. The present study assesses the cost
effectiveness of degarelix compared to leuprolide for PCa patients with increased
CV risk. METHODS: This analysis is based on a pooled analysis of six phase III,
randomized, controlled trials comparing the GnRH agonists leuprolide and
goserelin with the GnRH antagonist degarelix. For the combined endpoint of CV
events or death a superiority of degarelix was determined with a Number-Needed-to
Treat of 12. From the perspective of German statutory health insurance, this
evaluation estimates and compares the additional drug costs of degarelix
treatment to the cost of one (avoided) CV event. The CV event costs were
estimated via emergency treatment and transportation, inpatient treatment, and
rehabilitation. The difference of these two cost pools divided by 12 yields the
average saving per patient and year. RESULTS: For every 12 PCa patients with CV
history that are treated with GnRH antagonists to prevent one CV event, there
will be additional drug costs in comparison with leuprolide treatment of ? 3111
per year. Costs of ? 8447 per year are prevented. Therefore, each patient with a
history of CV who is treated with degarelix instead of a leuprolide generates
savings of ? 445 per patient and year. CONCLUSIONS: Compared to leuprolide,
degarelix is cost effective for patients with increased CV risk.
PMID- 28405704
TI - Expression of Histophilus somni IbpA DR2 protective antigen in the diatom
Thalassiosira pseudonana.
AB - Increasing demand for the low-cost production of valuable proteins has stimulated
development of novel expression systems. Many challenges faced by existing
technology may be overcome by using unicellular microalgae as an expression
platform due to their ability to be cultivated rapidly, inexpensively, and in
large scale. Diatoms are a particularly productive type of unicellular algae
showing promise as production organisms. Here, we report the development of an
expression system in the diatom Thalassiosira pseudonana by expressing the
protective IbpA DR2 antigen from Histophilus somni for the production of a
vaccine against bovine respiratory disease. The utilization of diatoms with their
typically silicified cell walls permitted development of silicon-responsive
transcription elements to induce protein expression. Specifically, we demonstrate
that transcription elements from the silicon transporter gene SIT1 are sufficient
to drive high levels of IbpA DR2 expression during silicon limitation and growth
arrest. These culture conditions eliminate the flux of cellular resources into
cell division processes, yet do not limit protein expression. In addition to
improving protein expression levels by molecular manipulations, yield was
dramatically increased through cultivation enhancement including elevated light
and CO2 supplementation. We substantially increased recombinant protein
production over starting levels to 1.2% of the total sodium dodecyl sulfate
extractable protein in T. pseudonana, which was sufficient to conduct preliminary
immunization trials in mice. Mice exposed to 5 MUg of diatom-expressed DR2 in
whole or sonicated cells (without protein purification) exhibited a modest immune
response without the addition of adjuvant.
PMID- 28405707
TI - [Therapeutic management of blunt testicular trauma].
AB - Testicular trauma is a rare emergency. While penetrating injuries need surgical
revision, blunt injuries may be treated conservatively. However, in case of
testicular rupture early surgical intervention increases the chance of testicular
preservation. Therefore, a meticulous urological diagnosis is important to avoid
complications and to reduce rates of secondary orchiectomy.
PMID- 28405709
TI - [SCARF osteotomy].
AB - Hallux valgus is one of the most common deformities of the lower extremity.
Multiple etiologies have been discussed, and various techniques have been
described. The SCARF osteotomy is indicated for moderate to severe hallux valgus
deformities. The technique historically used by carpenters allows immediate
postoperative weight bearing and also entails the possibility to correct the
distal metatarsal articular angle by rotation of the osteotomy. The SCARF
osteotomy has also been successfully used in revision surgeries.
PMID- 28405710
TI - [Distal osteotomy for the treatment of hallux valgus (Chevron osteotomy)].
AB - Distal osteotomies, like the Chevron osteotomy, is indicated for mild to moderate
hallux valgus deformities. Splayfoot, painful pseudoexostosis, and transfer
metatasalgia are observed in the clinical examination. Radiographic examination
should be done with weight bearing in two planes. Preoperatively the
intermetatarsal (IM), hallux valgus, and distal metatarsal articular (DMAA)
angles should be measured. The operative technique is based on soft tissue and
bony correction. Modifications of the osteotomy allow a shortening, lengthening,
or neutral correction of the first metatarsal. With a modified Chevron osteotomy,
an increased DMAA can be also corrected.
PMID- 28405708
TI - [Supramalleolar osteotomy in asymmetric ankle osteoarthritis : Short-term
clinical and radiographic results].
AB - BACKGROUND: The main indication for the supramalleolar osteotomy is asymmetric
ankle osteoarthritis with concomitant supramalleolar valgus or varus deformity.
The aim of this prospective study was to analyze short-term clinical and
radiographic outcomes in patients with asymmetric ankle osteoarthritis. METHODS:
A total of 16 patients with asymmetric ankle osteoarthritis and concomitant
supramalleolar deformity - 7 patients with valgus deformity, 9 patients with
varus deformity - were treated. Intraoperative and postoperative complications
were recorded and analyzed. The clinical and radiographic outcomes were assessed
after a mean follow-up of 3.6 +/- 1.1 years. RESULTS: In 10 of 16 patients,
removal of hardware was performed. The AOFAS hindfoot score increased
significantly after surgery. All categories of the SF-36 score showed significant
improvement. The average range of motion also increased significantly.
Radiographic assessment showed neutral hindfoot alignment at the latest follow
up. The postoperative clinical outcomes were comparable in both patient groups.
The time until complete osseous union was significantly longer in patients with
opening wedge osteotomy. CONCLUSION: This prospective study demonstrated
encouraging short-term results in patients with asymmetric ankle osteoarthritis
who underwent supramalleolar osteotomy. In progressive ankle osteoarthritis,
joint-nonpreserving treatment options including total ankle replacement or ankle
arthrodesis should be discussed.
PMID- 28405711
TI - Effect of clozapine on ketamine-induced deficits in attentional set shift task in
mice.
AB - RATIONALE: Clozapine (CLZ) is an effective treatment for schizophrenia, producing
improvements in both negative symptoms and cognitive impairments. Cognitive
impairments can be modelled in animals by ketamine (KET) and assessed using the
attentional set-shift task (ASST). OBJECTIVE: Our first aim was to determine
whether CLZ improves cognitive function and reverses KET-induced cognitive
impairments using the ASST. Our second aim was to assess dose dependency of these
effects. RESULTS: Our findings demonstrate that acute as well as sub-chronic
administration of KET cause cognitive deficits observed as increase in number of
trails and errors to reach the criterion in the EDS phase. CLZ 0.3 mg/kg reversed
the effects of both acute and sub-chronic KET, with no effects on locomotor
activity. However, clozapine's effect after sub-chronic administration of dose
0.3 mg/kg was not as explicit as in the case of acute treatment. Moreover,
administration of 1 mg/kg CLZ to KET-treated mice induced or enhanced deficits in
the extra-dimensional shift phase compared to 1 mg/kg CLZ administration to mice
not receiving KET. Locomotor activity test showed sedation effects of CLZ 1 mg/kg
after acute treatment; therefore, effect of CLZ 1 mg/kg on KET-induced cognitive
deficits was not evaluated in the attentional set-shift task (ASST) test.
CONCLUSIONS: The present findings support dose-dependent effects of CLZ to
reverse KET-induced cognitive deficits. The observed dose dependency may be
mediated by activation of different receptors, including monomers and/or
heterodimers.
PMID- 28405712
TI - Emergence of New sRNAs in Enteric Bacteria is Associated with Low Expression and
Rapid Evolution.
AB - Non-coding small RNAs (sRNAs) are critical to post-transcriptional gene
regulation in bacteria. However, unlike for protein-coding genes, the
evolutionary forces that shape sRNAs are not understood. We investigated sRNAs in
enteric bacteria and discovered that recently emerged sRNAs evolve at
significantly faster rates than older sRNAs. Concomitantly, younger sRNAs are
expressed at significantly lower levels than older sRNAs. This process could
potentially facilitate the integration of newly emerged sRNAs into bacterial
regulatory networks. Furthermore, it has previously been difficult to trace the
evolutionary histories of sRNAs because rapid evolution obscures their original
sources. We overcame this challenge by identifying a recently evolved sRNA in
Escherichia coli, which allowed us to determine that novel sRNAs could emerge
from vestigial bacteriophage genes, the first known source for sRNA origination.
PMID- 28405713
TI - Vaginal vault prolapse in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome:
a video case presentation.
AB - INTRODUCTION AND HYPOTHESIS: Several reports have described vaginal prolapse in
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome patients after creation of a
neovagina. To our knowledge, no reports of primary vaginal prolapse of a blind
pouch without previous intervention, or surgery for this condition, have been
described. METHODS: In this case report, we describe a 19-year-old woman with
MRKH and complete prolapse of her shortened vaginal pouch. Surgical correction
utilizing permanent suture-based sacrospinous ligament fixation was performed.
RESULTS: The patient had a successful outcome. CONCLUSIONS: Sacrospinous ligament
fixation provided a safe and effective method for the management of vaginal pouch
prolapse. Long-term follow-up is planned. To our knowledge, this is the first
report describing surgical repair of primary prolapse of a blind vaginal pouch in
the setting of MRKH.
PMID- 28405714
TI - Recessive male sterility in cabbage (Brassica oleracea var. capitata) caused by
loss of function of BoCYP704B1 due to the insertion of a LTR-retrotransposon.
AB - KEY MESSAGE: The LTR-retrotransposon insertion in BoCYP704B1 is proved to be the
primary cause of the male sterility in cabbage. Effective allele-specific markers
were developed for marker-assisted selection of male sterile gene. 83121A is a
spontaneous male sterile mutant identified from cabbage. Genetic analysis
indicated that male sterility is controlled by a single recessive gene. Pollen
wall formation in the 83121A mutant was severely defective, with a lack of
sporopollenin or exine. To understand the mechanisms of male sterility in 83121A,
transcription analysis using RNA-Seq was carried out in the buds of the male
sterile line 83121A and the male fertile line 83121B, which are near-isogenic
lines differing only in the fertility trait. Via expression analysis of
differentially expressed genes involved in pollen exine development before the
bicellular pollen stage, BoCYP704B1 was identified as a candidate gene, which was
approximately downregulated 30-fold in 83121A. BoCYP704B1 is a member of the
evolutionarily conserved CYP704B family, which is essential for sporopollenin
formation. The BoCYP704B1 transcript is specifically detected in the developing
anthers of wild-type cabbage. Further sequence analysis revealed that a 5424-bp
long terminal repeat-retrotransposon (LTR-RT) was inserted into the first exon of
BoCYP704B1 in 83121A, which is not found in wild-type plants. The insertion of
LTR-RT not only reduced the expression of BoCYP704B1 but also altered structure
of protein encoded by BoCYP704B1. Moreover, linkage analysis showed that the
homozygotic mutational BoCYP704B1 always cosegregated with male sterility. These
data suggest that the LTR-RT insertion in BoCYP704B1 hinders sporopollenin
formation in 83121A leading to male sterility. The allele-specific markers
developed in this study were effective for marker-assisted selection of the male
sterile gene.
PMID- 28405715
TI - [Robot-assisted liver resection].
AB - Robotic liver resection can overcome some of the limitations of laparoscopic
liver surgery; therefore, it is a promising tool to increase the proportion of
minimally invasive liver resections. The present article gives an overview of the
current literature. Furthermore, the results of a nationwide survey on robotic
liver surgery among hospitals in Germany with a DaVinci system used in general
visceral surgery and the perioperative results of two German robotic centers are
presented.
PMID- 28405716
TI - [Intraoperatively unrecognized central bile duct injury : In open converted,
laparoscopically begun cholecystectomy].
PMID- 28405717
TI - [Differential indications for ileoanal pouch anastomosis : Ulcerative colitis,
familial adenomatous polyposis, synchronous colorectal cancer - Crohn's disease,
constipation].
AB - Ileoanal pouch anastomosis is the procedure of choice for patients with drug
refractory ulcerative colitis, indeterminate colitis and familial adenomatous
polyposis (FAP). In selected patient groups this procedure is a treatment option
for patients with Crohn's disease, hereditary nonpolyposis colorectal cancer
(HNPCC), synchronous colorectal cancer and for severe colorectal constipation
refractory to conservative drug treatment. The pouch procedure provides the
opportunity to avoid a permanent ileostomy. The majority of surgeons prefer the
ileal J-pouch as the construction is the easiest to perform and complications and
dysfunction rates are low. Due to functional reasons most pouch surgeons favor a
circular stapled ileoanal pouch anastomosis. The more radical proctocolectomy can
produce sensory defects in the anal canal with subsequent soiling and
incontinence. Studies have shown that even after proctocolectomy residual rectal
mucosa was found in the anal canal. Therefore, the functionally important
anorectal transitional zone should be preserved if possible. Ulcerative colitis
can be "healed" with proctocolectomy; however, pouchitis can still occur in one
third of the patients. Patients must be informed about the risk of pouchitis and
a multidisciplinary monitoring and treatment strategy must be available. In
Crohn's disease the ileoanal pouch survival rate of 80% in the long-term follow
up is surprisingly good despite an increased postoperative complication rate. The
anal pouch anastomosis is the standard operation in patients with drug refractory
ulcerative colitis, indeterminate colitis and FAP. Synchronous colorectal cancer,
HNPCC and severe therapy refractive constipation represent rare indications for
proctocolectomy where decisions must be made on an individual basis.
PMID- 28405718
TI - [Value of surgical shunt procedures for portal hypertension].
PMID- 28405719
TI - [Pruritus of the scalp : Simply pulling out your hair?]
AB - Scalp pruritus is a frequent symptom and can be caused by dermatologic diseases,
contact allergies, neurologic, psychiatric/somatoform and systemic diseases. In
daily clinical practice scalp pruritus is a diagnostic and therapeutic challenge,
especially if no detectable lesions are present. A detailed patient history and
the inspection of scalp and the skin of the whole body are essential for
diagnosis. Depending on the clinical findings, further dermatological diagnostic
tests, laboratory analysis, imaging techniques and, where necessary, an
interdisciplinary specific diagnostic check-up should be performed. Therapy
comprises the treatment of the underlying disease, symptomatic antipruritic
treatments such as topical treatment and if applicable systemic treatment. All
this should be performed considering the individual situation especially the
patient's hair growth and density.
PMID- 28405720
TI - Ceramide synthase 2 deficiency aggravates AOM-DSS-induced colitis in mice: role
of colon barrier integrity.
AB - Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease
like ulcerative colitis. The molecular mechanisms are not well understood, but
likely involve dysregulation of membrane composition, fluidity, and permeability,
which are all essentially regulated by sphingolipids, including ceramides of
different chain length and saturation. Here, we used a loss-of-function model
(CerS2+/+ and CerS2-/- mice) to investigate the impact of ceramide synthase 2, a
key enzyme in the generation of very long-chain ceramides, in the dextran sodium
salt (DSS) evoked model of UC. CerS2-/- mice developed more severe disease than
CerS2+/+ mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2
strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly
increased long-chain ceramides and sphinganine in plasma and colon tissue. In
naive CerS2-/- mice, the expression of tight junction proteins including ZO-1 was
almost completely lost in the colon epithelium, leading to increased membrane
permeability. This could also be observed in vitro in CerS2 depleted Caco-2
cells. The increase in membrane permeability in CerS2-/- mice did not manifest
with apparent clinical symptoms in naive mice, but with slight inflammatory signs
such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led
to a further deterioration of membrane integrity and to severe clinical symptoms
of the disease. This was associated with stronger upregulation of cytokines in
CerS2-/- mice and increased infiltration of the colon wall by immune cells,
particularly monocytes, CD4+ and Th17+ T-cells, and an increase in tumor burden.
In conclusion, CerS2 is crucial for the maintenance of colon barrier function and
epithelial integrity. CerS2 knockdown, and associated changes in several
sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an
increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon,
may weaken endogenous defense against the endogenous microbiome.
PMID- 28405722
TI - [Legal cases in emergency medicine - the Swiss legal situation].
PMID- 28405723
TI - [Guideline-conform surgery of inguinal hernia].
PMID- 28405721
TI - Genome editing: a robust technology for human stem cells.
AB - Human pluripotent stem cells comprise induced pluripotent and embryonic stem
cells, which have tremendous potential for biological and therapeutic
applications. The development of efficient technologies for the targeted genome
alteration of stem cells in disease models is a prerequisite for utilizing stem
cells to their full potential. Genome editing of stem cells is possible with the
help of synthetic nucleases that facilitate site-specific modification of a gene
of interest. Recent advances in genome editing techniques have improved the
efficiency and speed of the development of stem cells for human disease models.
Zinc finger nucleases, transcription activator-like effector nucleases, and
clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated system are powerful tools for editing DNA at specific loci. Here, we
discuss recent technological advances in genome editing with site-specific
nucleases in human stem cells.
PMID- 28405724
TI - ?
PMID- 28405725
TI - The posterolateral approach for fluoroscopy-guided tibiotalar joint injection.
AB - OBJECTIVE: To report a novel technique for tibiotalar joint injection that
utilizes a posterolateral approach, including indications and technical
considerations. METHODS: The posterolateral approach for tibiotalar injection is
similar to that used in posterior subtalar joint injections. Using this
technique, the tibiotalar joint space is accessed by directing the needle
anterosuperiorly beneath the fibula until the posterior aspect of the talar dome
has been reached. A retrospective review was conducted of all posterolateral
approach tibiotalar joint injections at our institution. RESULTS: Eight patients
underwent 12 technically successful therapeutic anesthetic/steroid tibiotalar
joint injections using the posterolateral approach under fluoroscopic guidance.
All eight patients had anterior predominant arthrosis with large osteophytes and
tibiotalar joint space narrowing. The injections were well tolerated without
evidence of complications. CONCLUSION: Posterolateral tibiotalar joint injection
offers an alternative to the more commonly used anterior approach, particularly
in cases of severe anterior predominant arthrosis. An additional advantage of
this technique is that the ankle stays in the same position between the initial
planning of the needle trajectory and the visualization of contrast flowing into
the joint.
PMID- 28405726
TI - Inter-heterogeneity and intra-heterogeneity of alphavbeta3 in non-small cell lung
cancer and small cell lung cancer patients as revealed by 68Ga-RGD2 PET imaging.
AB - PURPOSE: Integrin alphavbeta3 is the therapeutic target of the anti-angiogenic
drug cilengitide. The objective of this study was to compare alphavbeta3 levels
in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients,
by using the positron emission tomography (PET) tracer 68Ga-labeled dimerized-RGD
(68Ga-RGD2). METHODS: Thirty-one patients with pathologically confirmed lung
cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were
acquired using 68Ga-RGD2.18F-FDG PET/CT images were also acquired on the
consecutive day as reference. The standard uptake values (SUV) and the
tumor/nontarget (T/NT) values were quantitatively compared. Expression of the
angiogenesis marker alphavbeta3 in NSCLC and SCLC lesions was analyzed by
immunohistochemistry. RESULTS: The 18F-FDG SUVmax and the SUVmean were not
significantly different between NSCLC and SCLC patients. The 68Ga-RGD2 uptake of
SCLC patients was at background levels in both SUV and T/NT measurements and was
significantly lower than that of NSCLC patients. The range value of 68Ga-RGD2
SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation
coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively.
Heterogeneity between primary lesions and putative distant metastases was also
observed in some NSCLC cases. Immunostaining showed that alphavbeta3 integrin was
expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples
had negative expression. CONCLUSIONS: The uptake of 68Ga-RGD2 in SCLC patients is
significantly lower than that in NSCLC patients, indicating a lower alphavbeta3
target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of
alphavbeta3 also exist in both NSCLC and SCLC. Such inter- and intra
heterogeneity of alphavbeta3 may potentially improve current applications of
alphavbeta3-targeted therapy and diagnostic imaging in lung cancer.
PMID- 28405727
TI - The role of 18F-FDG PET/CT in the detection of osteosarcoma recurrence.
AB - AIM: The aim of this study was to investigate the diagnostic accuracy of 18F-FDG
PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate
surgical therapy. METHODS: Inclusion criteria were: a) adequate surgical
treatment for proven osteosarcoma and documented complete remission after
therapy; b) 18F-FDG-PET/CT performed during follow-up for clinical/diagnostic
suspicion of relapse; c) new surgical treatment with excision of the suspected
lesions; d) histological validation of 18F-FDG-PET/CT findings. Thirty-seven
patients matching all inclusion criteria were retrospectively enrolled (20 men
and 17 female). Primary surgical treatment consists of resection (31 cases) or
amputation (six cases). 18F-FDG-PET/CT performance was assessed with a per
patient and per-site evaluation of sensitivity, specificity, accuracy, positive
predicting value (PPV), and negative predicting value (NPV). The sites of relapse
were classified as local, lung, lymphnodes (LNs), and distant (other skeletal
segments and/or distant soft tissue). The disease-free survival (DFS) and the
overall survival (OS) after 18F-FDG PET/CT were evaluated. RESULTS: 18F-FDG
PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed
in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only
in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology
resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions
were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight
distant metastatic lesions). On a per-patient analysis 18F-FDG-PET/CT showed a
sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a
per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%,
93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean
follow-up after 18F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37)
of patients were death with disease, 38% (14/37) were alive with disease, and 43%
(16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60
months, respectively. CONCLUSION: 18F-FDG-PET/CT showed valuable results for
detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after
treatment, particularly in the detection of local relapse and lung metastasis.
PMID- 28405728
TI - Clinical feasibility of 90Y digital PET/CT for imaging microsphere
biodistribution following radioembolization.
AB - PURPOSE: The purpose of this study was to evaluate the clinical feasibility of
next generation solid-state digital photon counting PET/CT (dPET/CT) technology
and imaging findings in patients following 90Y microsphere radioembolization in
comparison with standard of care (SOC) bremsstrahlung SPECT/CT (bSPECT/CT).
METHODS: Five patients underwent SOC 90Y bremsstrahlung imaging immediately
following routine radioembolization with 3.5 +/- 1.7 GBq of 90Y-labeled glass
microspheres. All patients also underwent dPET/CT imaging at 29 +/- 11 h
following radioembolization. Matched pairs comparison was used to compare image
quality, image contrast and 90Y biodistribution between dPET/CT and bSPECT/CT
images. Volumetric assessments of 90Y activity using different isocontour
thresholds on dPET/CT and bSPECT/CT images were also compared. RESULTS: Digital
PET/CT consistently provided better visual image quality and 90Y-to-background
image contrast while depicting 90Y biodistribution than bSPECT/CT. Isocontour
volumetric assessment using a 1% threshold precisely outlined 90Y activity and
the treatment volume on dPET/CT images, whereas a more restrictive 20% threshold
on bSPECT/CT images was needed to obtain comparable treatment volumes. The use of
a less restrictive 10% threshold isocontour on bSPECT/CT images grossly
overestimated the treatment volume when compared with the 1% threshold on dPET/CT
images. CONCLUSIONS: Digital PET/CT is clinically feasible for the assessment of
90Y microsphere biodistribution following radioembolization, and provides better
visual image quality and image contrast than routine bSPECT/CT with comparable
acquisition times. With further optimization and clinical validation, dPET
technology may allow faster and more accurate imaging-based assessment of 90Y
microsphere biodistribution.
PMID- 28405729
TI - Dietary acid load, trabecular bone integrity, and mineral density in an ageing
population: the Rotterdam study.
AB - : We studied the relation between a diet that is high in acid-forming nutrients
(e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone
structure. We showed a negative relation, which was more prominent if proteins
were of animal rather than of vegetable origin and if intake of dietary fibre was
high. INTRODUCTION: Studies on dietary acid load (DAL) and fractures have shown
inconsistent results. Associations between DAL, bone mineral density (BMD) and
trabecular bone integrity might play a role in these inconsistencies and might be
influenced by renal function and dietary fibre intake. Therefore, our aim was to
study (1) associations of DAL with BMD and with the trabecular bone score (TBS)
and (2) the potential influence of renal function and dietary fibre in these
associations. METHODS: Dutch individuals aged 45 years and over (n = 4672)
participating in the prospective cohort of the Rotterdam study were included.
Based on food frequency questionnaires, three indices of DAL were calculated: the
net endogenous acid production (NEAP) and the ratios of vegetable or animal
protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD
were derived from dual-energy X-ray absorptiometry measurements. RESULTS:
Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated
with low TBS (standardized beta (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11,
0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non
linear and differently shaped. Unfavourable associations between NEAP, BMD and
TBS were mainly present in subgroups with high fibre intake. CONCLUSIONS: High
NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS
were non-linear and differently shaped. No significant associations of DAL with
BMD were observed, nor was there any significant interaction between DAL and
renal function. Mainly in participants with high intake of dietary fibre, DAL
might be detrimental to bone.
PMID- 28405730
TI - Sex-related variations in cortical and trabecular bone of the femoral neck in an
elderly Chinese population.
AB - : Quantitative computed tomography (QCT) was used to investigate sex-related
variations in cortical and trabecular bone of the femoral neck. Cortical bone
thickness of women in the superior quadrant was thinner than that of men, and the
cortex in all four quadrants was negatively associated with age in women.
INTRODUCTION: This cross-sectional study aimed to investigate sex-related
similarities and differences in femoral neck structure in an elderly Chinese
population by QCT bone investigational toolkit (BIT) analysis. METHODS: This
study included 207 male (67.9 +/- 7.7 years; range, 55-87 years) and 400 female
subjects (68.0 +/- 8.7 years; range, 55-96 years). BIT module was used to measure
cortical and trabecular bone in anatomic quadrants of the femoral neck.
Measurements of cortical thickness (Ct.Th), cortical vBMD (Ct.vBMD), trabecular
vBMD (Tb.vBMD), and integral vBMD (It.vBMD) at the femoral neck were determined
in four anatomical sectors. RESULTS: The greatest difference between sexes, after
adjusting for age, height, and weight, was in Ct.Th of Quadrant Supero-anterior
(SA), which was 27.4% lower in women (p<0.001). Ct.Th of Quadrant Supero
posterior (SP) was 15.1% lower in women (p = 0.027). Ct.Th and Tb.vBMD in all
four quadrants appeared to be negatively associated with age in females, whereas
no significant relationship was observed in males, except Ct.Th of Quadrant SP.
CONCLUSIONS: The superior femoral neck geometry between males and females was
significantly different, even after adjustment for body size and age, and the sub
regional cortical and trabecular bone negatively age-related changes in women
indicated that women apparently have a more vulnerable geometrical outcome with
age for fractures than men.
PMID- 28405731
TI - Reduced bone mass and preserved marrow adipose tissue in patients with
inflammatory bowel diseases in long-term remission.
AB - : Bone marrow adipose tissue has not been studied in patients with inactive
inflammatory bowel disease. We found that these patients have preserved marrow
adiposity even with low bone mass. Factors involved in bone loss in active
disease may have long-lasting effects but do not seem to affect bone marrow
adiposity. INTRODUCTION: Reduced bone mass is known to occur at varying
prevalence in patients with inflammatory bowel diseases (IBD) because of
inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in
these patients as the result of an imbalanced relationship between osteoblasts
and adipocytes in bone marrow. This study aimed to evaluate for the first time
bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD
patients characterized by long-term, steroid-free remission. METHODS: Patients
with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and
controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear
magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment.
RESULTS: Both the CD and UC subgroups showed significantly higher proportions of
patients than controls with Z-score <=-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%;
p = 0.02), but not at other sites. The proportions of CD patients with a T-score
?-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C
16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There
were no statistically significant differences between IBD patients and controls
regarding BMAT at L3 (C 28.62 +/- 8.15%; CD 29.81 +/- 6.90%; UC 27.35 +/- 9.80%;
p = 0.67). CONCLUSIONS: IBD patients in long-term, steroid-free remission may
have a low bone mass in spite of preserved BMAT. These findings confirm the
heterogeneity of bone disorders in IBD and may indicate that factors involved in
bone loss in active disease may have long-lasting effects on these patients.
PMID- 28405732
TI - Determination of forces on a split palatal screw after rapid maxillary expansion.
AB - OBJECTIVES: Aim of this study was to develop a finite element model of the forces
that patients with rapid maxillary expansion bear and to validate it by a
mechanical test. METHODS: Computer-aided design models of the metallic screw and
polymeric splint were modelled and discretized. Two forces were generated and
considered independently: F1 at the temporary molar (2.5 N) and F2 at the
permanent molar (2.5 N). The results of the finite element analysis were used to
define the strain values which the anterior and posterior arms of the rapid
maxillary expansion appliance bore as a linear function of F1-F2 by calculating
the strain-force coefficient delta ij . Two strain gauge rosettes were attached
to an appliance which was placed in an XY motorized stage to reproduce the same
forces used in the finite element analysis. Once the system was validated, the
matrix was inverted to determine forces F1 and F2 that a group of 40 patients
underwent (median age 8.33 years, standard deviation 1.86 years) for 75 days,
using their strain values. The parents of the patients activated a quarter turn
(0.20 mm) twice a day until 50% transversal overcorrection was achieved. RESULTS:
Finite element analysis showed that the effects of the forces on stress at the
location of the arms were notably different. There was a satisfactory correlation
between finite element analysis predictions and in vitro values. Dissipation of
F1 and F2 in patients was predicted to be 62.5 and 80%, respectively, after 75
days of retention. CONCLUSION: These results back the finite element analysis
model for force prediction.
PMID- 28405733
TI - Association of IL-1beta, IL-1Ra and FABP1 gene polymorphisms with the metabolic
features of polycystic ovary syndrome.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS), a highly prevalent endocrinopathy
is currently being designated as chronic low grade inflammatory state. IL-1beta,
IL-1Ra and FABP1 are critical mediators of inflammatory processes and are
speculated to play a role in the pathogenesis of PCOS. The aim of this study was
to study the association of IL-beta, IL-1Ra and FABP1 gene polymorphisms with
PCOS and related metabolic features. SUBJECTS: 95 PCOS and 45 age matched healthy
control subjects were enrolled in this study. METHODS: Polymorphism in genes IL
1beta, IL-1Ra and FABP1 was studied by PCR, PCR-RFLP and sequencing methods,
respectively. Hormonal and lipid profiles were evaluated for all the subjects.
RESULTS: Hormonal and lipid profiles showed significant differences between PCOS
and control subjects. Allele and genotype frequencies of IL-1beta, IL-1Ra and
FABP1 gene polymorphisms did not vary between the control and PCOS group.
However, T allele of C[-511]T variant of IL-1beta, allele II in intron 2 of IL
1Ra and A allele of A/G variant of FABP1 (rs2197076) showed significant
association with many metabolic features associated with PCOS. CONCLUSIONS:
Polymorphism in genes encoding cytokines and proteins involved in lipid
metabolism can provide insights into the genetics of the disease and may
contribute to assess the associated risk of cardiovascular diseases (CVD),
dyslipidemia and metabolic syndrome (MetS) associated with PCOS.
PMID- 28405734
TI - Genetic association between TAP1 and TAP2 polymorphisms and ankylosing
spondylitis: a systematic review and meta-analysis.
AB - OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease.
The transporter associated with antigen processing (TAP) has been identified to
play an important role in immune response as well as the HLA-associated diseases.
The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and
TAP2) polymorphisms to the risk of AS. METHODS: Meta-analyses were performed
between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2
(TAP2-379, -565, and -665) and AS. RESULTS: The meta-analyses were involved with
6 studies with 415 cases and 659 controls. Significant association was found
between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined
control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09-1.80; TAP1-637Gly:
p = 0.002, OR = 1.48, 95% CI 1.15-1.91; p = 0.03, OR = 1.38, 95% CI 1.04-1.84).
Subgroup analysis shown that significant association was only found in AS when
compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95%
CI 1.14-2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15-2.02; p = 0.02, OR =
1.56, 95% CI 1.09-2.24), but not in AS when compared with HLA-B27-positive
controls (p > 0.05). Moreover, no significant associations were found between
haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p >
0.05). CONCLUSIONS: TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be
associated with AS.
PMID- 28405735
TI - Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6
trinitrochlorobenzene associated with attenuation of skin swelling.
AB - OBJECTIVES: Contact dermatitis model involving repeated application of hapten is
used as a tool to assess dermatitis, as characterized by thickening. Involvement
of cell proliferation, elicited by repeated hapten-stimulation, in this swelling
has been unclear. Curcumin is reported to reduce inflammation. We examined
involvement of cell proliferation and the role of extracellular regulated kinase
(ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We
also examined the effects of curcumin in this model. METHODS: Mice were
sensitized with TNCB to the abdominal skin. Then, they were challenged with TNCB
to the ear three times. The ERK activation inhibitor U0126 or curcumin was
applied 30 min before each TNCB challenge. RESULTS: TNCB challenge-induced
increased epidermal cell number and dermal thickening. Gene expressions of
epithelial mitogen (EPGN), amphiregulin (AREG) and heparin-binding-epidermal
growth factor (HB-EGF) were increased in the ears after the last TNCB challenge.
Ki-67 immunoreactivity was increased in the dermis in TNCB-challenged ears. TNCB
induced swelling was inhibited by U0126 and curcumin. Curcumin also attenuated
TNCB-induced ERK phosphorylation and expression of EPGN and AREG genes.
CONCLUSION: Ear swelling induced by TNCB challenge might be mediated, in part, by
the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin.
PMID- 28405737
TI - The prognostic significance of stapler doughnuts' examination at low anterior
resection for rectal cancer.
PMID- 28405738
TI - Evaluation of miR-506 and miR-4316 expression in early and non-invasive diagnosis
of colorectal cancer.
AB - PURPOSE: Examination of the entire colon by colonoscopy remains the golden
standard for screening of colorectal cancer (CRC). However, patients are
reluctant to perform invasive colonoscopies because of interference with their
intimacy. Therefore, the potential use of non-invasive analysis of microRNAs
expression in liquid biopsy as a novel biomarker for early CRC has investigated
in several studies. In this study, we analyzed the expression of two novel
microRNAs: miR-506 and miR-4316, which have never been examined in CRC. METHODS:
Plasma samples were collected from 56 patients (median age of 68 years) with
operable colorectal cancer and from 70 healthy individuals (median age of 59
years). Expression of plasma microRNAs was evaluated by quantitative reverse
transcription polymerase chain reaction using Eco real-time PCR device (Illumina,
USA). RESULTS: We found a significant elevated expression of both examined
microRNAs in early CRC patients when compared to those in healthy individuals (p
= 0.0054 for miR-506 and p = 0.0025 for miR-4316). The expression of miR-506 and
miR-4316 did not depend on gender, age, disease stage, and tumor localization of
CRC patients. ROC curve analysis showed that both examined microRNAs could
differentiate early stage colorectal cancer from healthy individuals with 76.8%
specificity and 60.7% sensitivity for miR-506 analysis and 76.8% specificity and
75% specificity for miR-4316 analysis. CONCLUSION: Our study revealed that
elevated expression of miR-506 and miR-4316 in peripheral blood were potential
molecular markers for early colorectal cancer.
PMID- 28405739
TI - Dermatological comorbidity in psoriasis: results from a large-scale cohort of
employees.
AB - The field of dermatological comorbidity in psoriasis is only passively explored
with contradictory results. Objective of this study was to further investigate
the complex field of psoriasis and associated skin diseases by identifying skin
comorbidity patterns in an extensive cohort of employees in Germany.
Retrospective analysis of data deriving from occupational skin cancer screenings
was conducted. From 2001 to 2014 German employees between 16 and 70 years from
different branches underwent single whole-body screenings by trained
dermatologists in their companies. All dermatological findings and need for
treatment were documented. Point prevalence rates and their 95% confidence
intervals were computed. Logistic regression analysis was performed to calculate
odds ratios (OR) of single dermatological diseases to occur together with
psoriasis controlled for age and sex. Data from 138,930 persons (56.5% male, mean
age 43.2) were evaluated. Psoriasis point prevalence was 2.0%. Of those 20.6% had
unmet treatment needs of their disease. Onychomycosis was the most frequent
dermatological comorbidity with a prevalence of 7.8%. Regression analysis found
rosacea (OR = 1.40, 95% CI 1.13-1.72) and telangiectasia (OR = 1.25, 95% CI 1.10
1.41) to be significantly associated with psoriasis. 17.2% of psoriasis patients
had at least one further finding requiring treatment. The highest treatment needs
were found for onychomycosis (3.4%), tinea pedis (3.1%), and verruca plantaris
(1.0%). It can be concluded that persons with psoriasis are at increased risk to
suffer from comorbid skin diseases, which should be considered in treatment
regimens. Particular attention should be paid to fungal diseases of the feet.
PMID- 28405740
TI - MRI is not reliable in diagnosing of concomitant anterolateral ligament and
anterior cruciate ligament injuries of the knee.
AB - PURPOSE: There has been a renewed interest in the anterolateral structures of the
knee, including description of the anterolateral ligament (ALL) as a distinct
structure. Recognizing injury to the ALL is challenging, particularly given the
subjective nature of physical examination. Consequently, focus has turned to
magnetic resonance imaging (MRI) to reach a preoperative diagnosis of this
region. The aim of this study was to examine the ability of 3-Tesla (3T) MRI to
identify the ALL in ACL-injured patients compared to a matched control group of
ACL-intact patients. The hypothesis was that the ALL would be more difficult to
identify in ACL-injured patients compared to ACL-intact patients. METHODS: A
prospective case control study was performed comparing 3T MRI scans of 63
patients with an ACL rupture with a control group of 64-patients without ACL
injury. An experienced musculoskeletal radiologist and an orthopaedic surgeon
evaluated the scans performed using standard knee protocols. The ALL was
considered in three regions for analysis: femoral, meniscal, and tibial. The
status of the ALL was determined as visualized or non-visualized, and the
integrity was assessed as intact, attenuated, or focal discontinuity. RESULTS:
The detection rate of at least a portion of the ALL was 41/64 (64%) in the
control group and 45/63 (72%) in the ACL-injured cohort, respectively. The entire
length of the ALL could only be identified in 15/64 (23%) of the control group
and 13/63 (21%) of the ACL-injured cases. In both groups, the visibility of the
ALL was poorest at the femoral region and greatest at the tibial regions. The
ALL, when visualized, was deemed to be intact in 55/63 (87%) of cases. Although
the inter-observer reliability was excellent for detection of the ALL in the
control group (kappa = 0.86), this decreased to only moderate reliability in the
ACL-injured group (kappa = 0.52). CONCLUSION: This study demonstrates that MRI
alone should not be relied upon to make a diagnosis of ALL injury in the setting
of concomitant ACL injury due to the inability to accurately visualize this
structure consistently in its entirety. To make a diagnosis of ALL injury or
anterolateral instability of the knee and clinical correlation remains essential.
LEVEL OF EVIDENCE: Case-control study, Level III.
PMID- 28405741
TI - Erratum to: Contributions of the anterolateral complex and the anterolateral
ligament to rotatory knee stability in the setting of ACL Injury: a roundtable
discussion.
PMID- 28405742
TI - CRISPR/Cas9-mediated deletion of lncRNA Gm26878 in the distant Foxf1 enhancer
region.
AB - Recent genome editing techniques, including CRISPR mutagenesis screens, offer
unparalleled opportunities to study the regulatory non-coding genomic regions,
enhancers, promoters, and functional non-coding RNAs. Heterozygous point
mutations in FOXF1 and genomic deletion copy-number variants at chromosomal
region 16q24.1 involving FOXF1 or its regulatory region mapping ~300 kb upstream
of FOXF1 and leaving it intact have been identified in the vast majority of
patients with a lethal neonatal lung disease, alveolar capillary dysplasia with
misalignment of pulmonary veins (ACDMPV). Homozygous Foxf1 -/- mice have been
shown to die by embryonic day 8.5 because of defects in the development of
extraembryonic and lateral mesoderm-derived tissues, whereas heterozygous Foxf1
+/- mice exhibit features resembling ACDMPV. We have previously defined a human
lung-specific enhancer region encoding two long non-coding RNAs, LINC01081 and
LINC01082, expressed in the lungs. To investigate the biological significance of
lncRNAs in the Foxf1 enhancer region, we have generated a CRISPR/Cas9-mediated
~2.4 kb deletion involving the entire lncRNA-encoding gene Gm26878, located in
the mouse region syntenic with the human Foxf1 upstream enhancer. Very recently,
this mouse genomic region has been shown to function as a Foxf1 enhancer. Our
results indicate that homozygous loss of Gm26878 is neonatal lethal with low
penetrance. No changes in Foxf1 expression were observed, suggesting that the
regulation of Foxf1 expression differs between mouse and human.
PMID- 28405743
TI - Short interval between two Pap smears: effect on the result of the second smear?
A prospective randomized trial.
AB - PURPOSE: A repeat Pap smear is sometimes necessary after a short time interval or
even immediately, when patients seek for a second opinion or due to study
participation. Only limited information is available on the possible impact of a
short interval between two Pap smears. Most institutions therefore practice a
minimum time span of 6-8 weeks before obtaining a second smear since a short
interval is commonly believed to be associated with an increase of false negative
results in the second smear. METHODS: Two consecutive Pap smears were obtained
from 81 women. 41 smears were processed using the conventional technique, whereas
liquid-based cytology was used in the remaining 40 women. Smears were
independently evaluated by four different cytopathologists. We analyzed the
effect of time interval, both processing techniques and inter-observer variance
in cytological evaluation. RESULTS: While the result of the second smear shows a
tendency towards a more benign outcome (odds ratio (OR) 1.436, 95% CI 0.972
2.121), this difference was not statistically significant (p = 0.07). No
significant differences were observed between conservative and liquid-based
cytology (OR 1.554, 95% CI 0.659-3.667, p = 0.31). There was considerable inter
observer variability, and the observer was a strong predictor of the cytological
result (OR 0.632-5.083, 95% CI 0.355-8.975, p < 0.01). CONCLUSIONS: We document a
tendency towards a more benign outcome without statistical significance in the
second smear. Inter-observer variability of different cytopathologists is high
and should be kept in mind when evaluating cytology results.
PMID- 28405744
TI - Long-term follow-up of fellow eye in patients with lamellar macular hole.
AB - BACKGROUND: To evaluate macular changes in fellow eyes of patients diagnosed with
lamellar macular hole (LMH) using spectral-domain optical coherence tomography
(SD-OCT) and blue fundus autofluorescence (B-FAF). METHODS: Fellow eyes of
patients diagnosed with a LMH were retrospectively evaluated on OCT. Best
corrected visual acuity (BCVA) and central foveal thickness (CFT) were recorded.
Corresponding B-FAF images, vitreo-macular relations, and type of epiretinal
membranes (ERMs) were also examined. RESULTS: Thirty-five patients were included.
At baseline, six fellow eyes (17%) showed a normal foveal profile, 26 (74%) had a
tractional ERM, and three cases (9%) revealed a bilateral LMH, one of them with a
lamellar hole-associated epiretinal proliferation (LHEP). A posterior vitreous
detachment (PVD) was present in 29 patients (83%), four (11%) had only a vitreo
papillary adhesion (VPA), and two (6%) had both vitreo-macular adhesion (VMA) and
VPA. After a mean follow-up of 4.6 +/- 1.9 years, one eye (3%) developed a
vitreous detachment from the macula with persistent VPA, and one developed a PVD
from a VPA with subsequent ERM formation. BCVA and mean CFT remained stable in 35
eyes (100%). Likewise, no B-FAF signal variations were detected. One patient
developed a LMH during the 3rd year of follow-up. CONCLUSIONS: Our data suggest
that the presence of a LMH in one eye does not increase significantly the risk of
developing the same condition in the fellow eye after 4 years. Bilateral
condition is uncommon, and an ERM is often detected in the fellow eye. LHEPs were
not observed in fellow eyes with foveal integrity, and all LHEPs observed (in
main and fellow eyes) were always associated with LMHs; this supports the
hypothesis that LHEP is a consequence and not a causative factor for LMHs. The
occurrence of a LMH in one fellow eye after 3 years follow-up may suggest that a
higher incidence of bilateral disease could develop in a longer time span.
PMID- 28405745
TI - Lethal albinic seedling, encoding a threonyl-tRNA synthetase, is involved in
development of plastid protein synthesis system in rice.
AB - KEY MESSAGE: An albinic rice is caused by mutation of threonyl-tRNA synthetase,
which is essential for plant development by stabilizing of NEP and PEP gene
expressions and chloroplast protein synthesis. Chloroplast biogenesis and
development depend on complex genetic mechanisms. Apart from their function in
translation, aminoacyl-tRNA synthetases (aaRSs) play additional role in gene
expression regulation, RNA splicing, and cytokine activity. However, their
detailed functions in plant development are still poorly understood. We isolated
a lethal albinic seedling (las) mutant in rice. Physiological and ultrastructural
analysis of las mutant plants revealed weak chlorophyll fluorescence, negligible
chlorophyll accumulation, and defective thylakoid membrane development. By map
based cloning we determined that the LAS allele gene encodes threonyl-tRNA
synthetase (ThrRS). LAS was constitutively expressed with relatively high level
in leaves. NEP-dependent gene transcripts accumulated in the developing
chloroplasts, while PEP-dependent transcripts were reduced in the las mutant.
This result indicated that PEP activity was impaired. Chloroplast-encoded protein
levels were sharply reduced in the las mutant. Biogenesis of chloroplast rRNAs
(16S and 23S rRNA) was arrested, leading to impaired translation and protein
synthesis. Together, our findings indicated that LAS is essential not only for
chloroplast development by stabilizing the NEP and PEP gene expression, but also
for protein synthesis and construction of the ribosome system in rice
chloroplasts.
PMID- 28405746
TI - Structured models of cell migration incorporating molecular binding processes.
AB - The dynamic interplay between collective cell movement and the various molecules
involved in the accompanying cell signalling mechanisms plays a crucial role in
many biological processes including normal tissue development and pathological
scenarios such as wound healing and cancer. Information about the various
structures embedded within these processes allows a detailed exploration of the
binding of molecular species to cell-surface receptors within the evolving cell
population. In this paper we establish a general spatio-temporal-structural
framework that enables the description of molecular binding to cell membranes
coupled with the cell population dynamics. We first provide a general theoretical
description for this approach and then illustrate it with three examples arising
from cancer invasion.
PMID- 28405748
TI - Translation of imaging biomarkers from clinical research to healthcare.
AB - The use of biomarkers for diagnostics of Alzheimer's disease (AD) has increased
over the last years in specialized care and experimental settings. With the
possibly upcoming availability of disease-modifying therapeutic agents, the
diagnostics and treatment of patients with cognitive impairment will change.
Biomarkers will be used as theranostic markers for case finding. The development
and evaluation of biomarkers can be framed in a phase model from preclinical
studies through trials in expert center settings to the evaluation of biomarkers
in primary care, up to testing the efficacy and the impact of biomarkers on the
healthcare system. Hippocampal volumetry is the most accepted and in-depth tested
biomarker for AD diagnostics and prediction of the course. Therefore, hippocampus
volumetry is used to illustrate the phase model of biomarker development and
present the milestones already achieved and questions still to be resolved.
PMID- 28405747
TI - Metabolic responses to different immune challenges and varying resource
availability in the side-blotched lizard (Uta stansburiana).
AB - The energetic cost of immunity depends on many factors, including the type of
challenge, the timing of the response, and the state of the animal. We measured
changes in the standard metabolic rates of side-blotched lizards (Uta
stansburiana Baird and Girard, 1852) in response to different immune challenges
and nutritional states. In the first experiment, lizards were randomly assigned
to one of four treatments: lipopolysaccharide (LPS) injection (to stimulate the
response to a pathogen), cutaneous biopsy (as a proxy to a superficial wound),
both injection and biopsy, or neither (control). Four and five days later, we
measured the standard metabolic rates of the lizards. In response to healing a
cutaneous wound, lizards reduced metabolic rate and lost body mass. Healing rate
was also inversely related to weight loss, but LPS had no effect on body mass or
metabolic rate. In the second experiment, a new set of lizards were randomly
assigned to a high-food or low-food diet and administered a cutaneous biopsy. As
in the first experiment, we observed a reduction in metabolic rate after
wounding; moreover, this decrease was positively correlated with the rate of
healing. We observed higher rates of metabolism in lizards that ate more food,
but food consumption was unrelated to the decrease in metabolic rate following
the biopsy. These experiments demonstrate the dynamic nature of the immune
response in response to immune challenge and the state of the organism.
PMID- 28405750
TI - Efficacy and Safety of Scarpa Fascia Preservation During Abdominoplasty: A
Systematic Review and Meta-analysis.
AB - INTRODUCTION: Scarpa fascia preservation might be a promising approach to reduce
seroma and other complications after abdominoplasty. However, the results
remained controversial. We conducted a systematic review and meta-analysis to
evaluate the efficacy and safety of scarpa fascia preservation in patients with
abdominoplasty. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane
library databases were systematically searched. Randomized controlled trials and
clinical controlled trials assessing the effect of scarpa fascia preservation
versus control (without scarpa fascia) during abdominoplasty were included. Two
investigators independently searched articles, extracted data, and assessed the
quality of included studies. The primary outcomes were seroma and
hematoma/bleeding. Meta-analysis was performed using random-effect model.
RESULTS: Four studies involving 630 patients were included in the meta-analysis.
Overall, compared with the control group, scarpa fascia preservation was
associated with a significant reduced seroma (OR 0.16; 95% CI 0.06-0.43; P =
0.0004), time until drain removal (std. mean difference = -0.92; 95% CI -1.31 to
0.54; P<0.00001;), drain output (std. mean difference = -0.92; 95% CI -1.38 to
0.45; P = 0.0001), and hospital stay (std. mean difference = -0.93; 95% CI -1.48
to -0.39; P = 0.0008), but it failed to alter hematoma/bleeding (OR 0.46; 95% CI
0.09-2.38; P = 0.36), infection (OR 0.38; 95% CI 0.11-1.25; P = 0.11), and suture
rupture (OR 0.67; 95% CI 0.12-3.73; P = 0.65) in patients with abdominoplasty.
CONCLUSIONS: Scarpa fascia preservation was associated with a significant
decreased seroma, time until drain removal, drain output, and hospital stay, but
could not change hematoma/bleeding, infection and suture rupture following
abdominoplasty. Scarpa fascia preservation should be recommended during
abdominoplasty. LEVEL OF EVIDENCE II: This journal requires that authors assign a
level of evidence to each article. For a full description of these Evidence-Based
Medicine ratings, please refer to the Table of Contents or the online
Instructions to Authors www.springer.com/00266 .
PMID- 28405749
TI - The anterior commissure of the human larynx revisited.
AB - BACKGROUND: The anterior commissure (AC) of the human larynx is usually
understood as an area of the glottis anteriorly situated between the two vocal
folds inserting to the thyroid cartilage (TC). The pattern of spread of AC
carcinoma could hypothesize that AC could include other structures of the ventral
larynx as developmental anatomy could demonstrate. METHODS: Ten adult larynx
specimens from donation program cadavers and 15 selected fetal specimens (from 11
to 34 weeks of amenorrhoea) were studied using microdissection and histological
serial sections stained with hematoxylin-eosin and reticuline. RESULTS: In adult
specimens, internal perichondrium of the TC was easily detached from the entire
lateral lamina but not from an intermediate lamina superiorly marked by the
superior thyroid notch. On this median band of TC is inserted the ventral
connective tissue of the three levels of the larynx: the ventral part of the
vocal folds with the anterior macula flava, the Broyle's epiglottic ligament, and
the subglottic part of the conoid ligament. In young fetuses (11-12 weeks),
intermediate lamina of TC joined at the glottic level but not at the supraglottic
level; in fetuses at 22-25 weeks, a meshwork of bundles of connective fibers
inserted to the intermediate lamina of TC. In fetuses at 33-34 weeks,
organization is practically identical to adult specimens. CONCLUSION: According
to the adult anatomical features and the organogenesis, the AC of the human
larynx could be anatomically defined ventrally as being made up of the
intermediate lamina of TC beneath the superior thyroid notch and dorsally the
ventral insertions of vocal folds with macula flava, supraglottic Broyle's
ligament, and subglottic conoid ligament leading to a "developmental" AC
definition which could better explain specific spreading of AC carcinoma.
PMID- 28405751
TI - Developmental validation of a 6-dye STR kit with 27 loci.
AB - The EX27 System is a 6-dye (i.e., FAM, HEX, TAMAR, ROX, VIG, and SIZ-500) kit
that combines the 24 autosomal STR loci (i.e., D3S1358, D13S317, D7S820, D16S539,
D1S1656, Penta E, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA,
D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391, FGA, D22S1045, D2S441, SE33)
with a Y-STR locus (DYS391), an Indel site (YIndel) and Amelogenin, which is
designed to amplify DNA from extracts as well as direct amplification from
substrates. The new system contains most of the widely used autosomal STR loci
around the world and is sensitive to the male component in mixtures and is more
accurate in gender determination owing to the DYS391 and YIndel.To demonstrate
the suitability for personal identification and parentage testing, the system was
validated for sensitivity of detection, species specificity, inhibitor tolerance,
DNA mixtures, reproducibility study, and concordance studies based on the SWGDAM
developmental validation guidelines. In view of the results, the EX27 System is a
robust and reliable amplification kit which can be used for human identification
testing.
PMID- 28405752
TI - Genetic characterization of an X-STR decaplex system in the State of Mato Grosso,
Brazil: distribution, forensic efficiency and population structure.
AB - Studies with X-STR loci show population genetic substructure, which makes
necessary the characterization of such markers in the different geographical
and/or ethnic populations. Therefore, this study assessed the distribution and
forensic efficiency of an X-STR decaplex system in the population of the State of
Mato Grosso, as well as analysed the population structure of this State based on
the aforementioned system. All X-STR markers were in Hardy-Weinberg equilibrium
and linkage equilibrium, and the DXS6809 was the most informative marker. The
power of discrimination value in females and males was 0.99999999995 and
0.9999994, respectively. Analysis of molecular variance indicated 1.10% (p <
0.00001) of heterogeneity among Europeans, Africans, Brazilians and other Latin
Americans, and in relation to such groups, the population of the State of Mato
Grosso showed lower genetic variation when compared with the Brazilian group (
0.10%, p = 0.67327). The genetic distance analysis showed lower values of F ST
(0.0004 <= F ST <= 0.00331), with non-significant p value (p > 0.00024), between
the populations of Mato Grosso and Mato Grosso do Sul, Parana and the Southeast
region of Brazil (except for one sample of Rio de Janeiro). F ST values with
significant p values (p <= 0.00024) were obtained between the population of Mato
Grosso and Iberian, African and some Latin American populations. The X-STR
decaplex system proved to be extremely useful in the population of the State of
Mato Grosso, and the data obtained does not show the need for a specific forensic
database for this State in relation to the Brazilian populations compared in this
study, except for population of Rio de Janeiro.
PMID- 28405753
TI - Relationships Between Land Use and Stream Nutrient Concentrations in a Highly
Urbanized Tropical Region of Brazil: Thresholds and Riparian Zones.
AB - Nutrient enrichment in streams due to land use is increasing globally, reducing
water quality and causing eutrophication of downstream fresh and coastal waters.
In temperate developed countries, the intensive use of fertilizers in agriculture
is a main driver of increasing nutrient concentrations, but high levels and fast
rates of urbanization can be a predominant issue in some areas of the developing
world. We investigated land use in the highly urbanized tropical State of Rio de
Janeiro, Brazil. We collected total nitrogen, total phosphorus, and inorganic
nutrient data from 35 independent watersheds distributed across the State and
characterized land use at a riparian and entire watershed scales upstream from
each sample station, using ArcGIS. We used regression models to explain land use
influences on nutrient concentrations and to assess riparian protection
relationships to water quality. We found that urban land use was the primary
driver of nutrient concentration increases, independent of the scale of analyses
and that urban land use was more concentrated in the riparian buffer of streams
than in the entire watersheds. We also found significant thresholds that
indicated strong increases in nutrient concentrations with modest increases in
urbanization reaching maximum nutrient concentrations between 10 and 46% urban
cover. These thresholds influenced calculation of reference nutrient
concentrations, and ignoring them led to higher estimates of these
concentrations. Lack of sewage treatment in concert with urban development in
riparian zones apparently leads to the observation that modest increases in urban
land use can cause large increases in nutrient concentrations.
PMID- 28405754
TI - Local Government Capacity to Respond to Environmental Change: Insights from Towns
in New York State.
AB - Local governments attempting to respond to environmental change face an array of
challenges. To better understand policy responses and factors influencing local
government capacity to respond to environmental change, we studied three
environmental issues affecting rural or peri-urban towns in different regions of
New York State: climate change in the Adirondacks (n = 63 towns), loss of open
space due to residential/commercial development in the Hudson Valley (n = 50),
and natural gas development in the Southern Tier (n = 62). Our analysis focused
on towns' progression through three key stages of the environmental policy
process (issue awareness and salience, common goals and agenda setting, policy
development and implementation) and the factors that affect this progression and
overall capacity for environmental governance. We found that-when compared to
towns addressing open space development and natural gas development-towns
confronted with climate change were at a much earlier stage in the policy process
and were generally less likely to display the essential resources, social
support, and political legitimacy needed for an effective policy response. Social
capital cultivated through collaboration and networking was strongly associated
with towns' policy response across all regions and could help municipalities
overcome omnipresent resource constraints. By comparing and contrasting municipal
responses to each issue, this study highlights the processes and factors
influencing local government capacity to address a range of environmental changes
across diverse management contexts.
PMID- 28405755
TI - [Sarcoidosis : Renal manifestations].
AB - Renal involvement in sarcoidosis is much more common than generally assumed from
old epidemiological studies and is often only detected when actively searched
for. Many patients with renal sarcoidosis present with no or only few symptoms.
The diagnostic work-up of sarcoidosis should always include a possible renal
involvement. In cases of impaired renal function, proteinuria or a pathological
urine sediment, a renal biopsy specimen should be obtained to assess the type,
severity and prognosis of the kidney disease. Treatment is primarily based on the
use of corticosteroids. Steroid-sparing agents, such as disease-modifying
antirheumatic drugs and infliximab can be applied; however, the evidence for
efficacy of these therapies is mostly based on case series and expert opinions.
Discontinuation of immunosuppression therapy bears a high risk of relapse.
PMID- 28405757
TI - [Acute, bilateral visual loss in a patient with IgA glomerulonephritis].
AB - We report on a 30-year-old male patient presenting with acute bilateral loss of
vision. Fundus examination showed bilateral retinal hemorrhages, cotton-wool
spots, macular edema and optic disk hyperemia. The blood pressure was elevated.
The patient was referred to the emergency department with the diagnosis of severe
stage IV hypertensive retinopathy. Further examination revealed a previously
unknown IgA glomerulonephritis with terminal renal failure and secondary blood
pressure derailment. Hypertensive retinopathy can be a first sign of acute renal
failure. In cases of hypertensive retinopathy the differential diagnosis
including systematic screening is of utmost importance.
PMID- 28405756
TI - [Maculopathy with optic nerve pits : Morphological criteria in SD - OCT].
AB - PURPOSE: Optic pit is a congenital anomaly with malformation similar to coloboma
of the optic disc. The cause of optic pit maculopathy is controversial. We used
high resolution OCT to investigate changes in the vitreoretinal and
vitreopapillary transition within optic pit eyes. METHODS: The vitreoretinal and
vitreo-papillary transition of 12 eyes was accurately analyzed using SD-OCT. We
registered the following criteria: liquefaction of prepapillary vitreous,
papillary vitreous traction, discontinuity within the hyaloid cortex and
communication spaces between pit and retinal edema. RESULTS: Communication gaps
between pit and retinal edema were identified in 8 eyes. 4 eyes had a papillary
vitreous traction. 4 showed a discontinuity in the hyaloid cortex. 2 of the 12
patients showed no maculopathy in SD-OCT. Those patients had an adjacent
papillary vitreous without prepapillary liquefaction. However all eyes showed
vitreous liquefaction at some stage premacullary or prepapillary. CONCLUSION: Yet
the cause of optic pit maculopathy is not clearly understood. High resolution OCT
imaging provides a very detailed assessment of the vitreoretinal transition
prepapillary and premacullary, however with limited penetration depth and
analyzation of deeper lying structures. Our observations suggest that
prepapillary liquefaction and pressure gradients within cerebrospinal and
intraokular pressure could be key factors.
PMID- 28405758
TI - [Prognosis and treatment of macular bleeding in neovascular age-related macular
degeneration].
AB - Macular bleeding is associated with an acute loss of visual function and is
frequently a complication of neovascular age-related macular degeneration. Blood
degradation products can lead to permanent retinal neuronal damage over time. The
extent of the bleeding is correlated to the coagulation status of the patient.
The treatment strategy depends on the age, size and exact location of the
bleeding. The spectrum of therapeutic options ranges from watchful waiting to
large scale vitrectomy with removal of subretinal mass bleeding.
PMID- 28405759
TI - [Statement of the Professional Association of German Ophthalmologists (BVA), the
German Ophthalmological Society (DOG) and the German Retina Society (RG): OCT
angiography in Germany : Presentation, nomenclature and future plans. Situation
January 2017].
PMID- 28405760
TI - [Acute unilateral impaired vision in a 26-year-old healthy woman].
PMID- 28405762
TI - Histopathological correlations to ureteral lesions visualized during
ureteroscopy.
AB - PURPOSE: To correlate ureteral lesions visualized during ureteroscopy with
histopathological findings. MATERIALS AND METHODS: Ureteral access sheaths (UAS)
sized 13/15 Fr. were inserted bilaterally in 22 laboratory pigs. During
retraction of the UAS with a semirigid ureteroscope inside, ureteral lesions were
evaluated and registered using the Post-ureteroscopic lesion scale (PULS).
Ureters were excised in vivo between the uretero-pelvic junction and the uretero
vesical junction. Embedded in paraffin, 4-um thick sections were step sectioned
at 250-300 um intervals and haematoxylin and eosin (HE) stained.
Histopathological scoring of ureteral wall lesions was subsequently performed
according to PULS. RESULTS: In 72.1% of ureters, the highest histopathological
score was at least 1 grade higher than the highest endoscopic PULS score. For 12
(27.9%) lesions, the difference was 2 scores higher, and for 1 (2.3%), it was 3
scores higher. The histopathological PULS grade was higher than the endoscopical
PULS grade at all minimum, quartile, and maximum scores. There was a significant
difference in the distribution of highest lesional scores between the endoscopic
and histopathological PULS (p = 0.002). The calculated mean of the highest scores
was 1.49 for endoscopic PULS and 2.51 for histopathological PULS (p < 0.0001).
CONCLUSION: Histopathological evaluation of ureteral wall lesions after UAS
placement revealed a significantly higher degree of severity than observed
endoscopically. Thus, endoscopy underestimated the histopathological extent of
the lesion in the majority of cases.
PMID- 28405761
TI - Adaptive responses of peripheral lateral line nerve fibres to sinusoidal wave
stimuli.
AB - Sensory adaptation is characterized by a reduction in the firing frequency of
neurons to prolonged stimulation, also called spike frequency adaptation. This
has been documented for sensory neurons of the visual, olfactory, electrosensory,
and auditory system both in response to constant-amplitude and to sinusoidal
stimuli, but has thus far not been described systematically for the lateral line
system. We recorded neuronal activity from primary afferent nerve fibres in the
lateral line in goldfish in response to sinusoidal wave stimuli. Depending on
stimulus characteristics, afferent fibre responses exhibited a distinct onset
followed by a decline in firing rate to an apparent steady-state level, i.e.,
they exhibited adaptation. The degree of adaptation, measured as the percent
decrease in firing rate between onset and steady-state, increased with stimulus
amplitude and frequency and with increasing steepness of the rising flank of the
stimulus. This may in part be due to the velocity and/or acceleration sensitivity
of the lateral line receptors. The time course of the response decline, i.e., the
time course of adaptation was best-fit by a power function. This is consistent
with the previous studies on spike frequency adaptation in sensory afferents of
weakly electric fish.
PMID- 28405763
TI - Five-year outcomes of thulium vapoenucleation of the prostate for symptomatic
benign prostatic obstruction.
AB - INTRODUCTION AND OBJECTIVES: To assess the 5-year outcomes of thulium
vapoenucleation of the prostate (ThuVEP) in patients with benign prostatic
obstruction (BPO) retrospectively. METHODS: Five-hundred patients were treated
with ThuVEP between January 2007 and January 2010 at our institution. Patients
were reassessed 1 and 5-years after ThuVEP with International Prostate Symptom
Score (IPSS), Quality of Life (QoL), urinary peak flow (Qmax), postvoid residual
volume (PVR), PSA and prostate volume. Patient data were expressed as median
(interquartile range). RESULTS: One-hundred and thirty-one patients completed the
5-year follow-up. According to preoperative prostate volume, patients were
divided into two groups: group A (<60 ml, n = 80) and B (>=60 ml, n = 51). IPSS,
QoL, Qmax, and PVR improved significantly at discharge and continued to do so
during 5-year follow-up (p <= 0.001). At 1-year follow-up, prostate volume had
decreased significantly (50 vs. 13 mL, p < 0.001) corresponding to a prostate
volume reduction of 80.8%. PSA was significantly reduced at 5-year (0.72 ug/l)
follow-up compared to preoperative PSA (3.39 ug/l, p <= 0.001). PSA-reduction
(total 77.1%) at 5-year follow-up was significantly different between group A
(70.2%) and B (83.5%) (p <= 0.006). IPSS was significantly lower in group B than
in A (2.5 vs. 6, p < 0.001) at 5-year follow-up. Bladder neck contractures (n =
4) and urethral strictures (n = 4) occurred in 3.1% of the patients each. Three
patients (2.3%) were re-treated for regrowth of prostatic tissue. CONCLUSIONS:
ThuVEP is a durable procedure with regard to micturition improvement and PSA
reduction. The reintervention rate after ThuVEP was low during long-term follow
up.
PMID- 28405764
TI - Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating
immune cells for microsatellite unstable and stable colorectal cancer.
AB - In this study, we investigated the clinical relevance of CD274 (PD-L1) protein
expression by tumor cells and tumor-infiltrating immune cells in colorectal
cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153
microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC)
analysis for the expression of CD274 and mismatch repair proteins. CD274
expression was evaluated in tumor cells at the center (TC) and periphery (TP),
and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained
for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of
tumor-infiltrating T cell density. Additionally, samples were screened for the B
Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274TC,
CD274TP, CD274IC, and CD274IP were observed in 43 (23.1%), 47 (25.3%), 107
(57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four
(2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile,
intratumoral heterogeneity of CD274 expression in tumor cells and immune cells
was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in
both MSI-H and MSS CRC, CD274IC and CD274IP were independently associated with
improved prognosis (P < 0.05), while BRAF mutation was associated with CD274TP,
poor differentiation, sporadic type, and hMLH1(-)/hMSH2(+)/hMSH6(+)/PMS2(-) in
MSI-H CRC (P < 0.006). In conclusion, CD274 expression in tumor-infiltrating
immune cells was an independent factor for improved prognosis in CRC patients. A
deeper understanding of CD274 status may yield improved responses to future CRC
immunotherapies.
PMID- 28405765
TI - Coexpressed modular gene expression reveals inverse correlation between immune
responsive transcription and aggressiveness in gastric tumours.
AB - The existing large number of gene expression profiles of tumour samples offers a
great advantage for the integrative functional genomic exploration of molecular
dysregulation in cancers. The clusters of genes (modules) derived from a gastric
cancer (GC) coexpression network were explored to understand their clinical and
functional significance. Among the modules derived from the GC mRNA expression
network, six modules were relatively highly expressed in diffuse type gastric
tumours. Elevated expression of genes related to extracellular matrix (ECM),
angiogenesis, collagen and intracellular cytoskeletal components and immune
response were identified in these modules. ECM-related modules exhibited an
inverse correlation with modules representing the expression of immune response
genes. A reduced expression of immune response genes was identified as the key
factor associated with the aggressive features of diffuse gastric tumours, which
is indicative of tumour progression involving the escape from immune surveillance
in diffuse tumours. A part of the identified aggressive factors was common
between intestinal and diffuse type tumours. The coexpressed modules and their
expression patterns delineate the fine transition involved in cancer progression
in the later stages of tumours. The identified modules could serve as surrogate
gene-sets, indicating the molecular staging of GC aggressiveness with underlying
biological interaction.
PMID- 28405766
TI - Characterization of cross-clade monoclonal antibodies against H5N1 highly
pathogenic avian influenza virus and their application to the antigenic analysis
of diverse H5 subtype viruses.
AB - H5N1 highly pathogenic avian influenza viruses (HPAIVs) are a threat to both
animal and public health and require specific and rapid detection for prompt
disease control. We produced three neutralizing anti-hemagglutinin (HA)
monoclonal antibodies (mAbs) using two clades (2.2 and 2.5) of the H5N1 HPAIV
isolated in Japan. Blocking immunofluorescence tests showed that each mAb
recognized different epitopes; 3B5.1 and 3B5.2 mAbs against the clade 2.5 virus
showed cross-clade reactivity to all 26 strains from clades 1, 2.2, 2.3.2.1,
2.3.2.1a, b, c and 2.3.4, suggesting that the epitope(s) recognized are
conserved. Conversely, the 1G5 mAb against the clade 2.2 virus showed reactivity
to only clades 1, 2.3.4 and 2.5 strains. An analysis of escape mutants, and some
clades of the H5N1 viruses recognized by 3B5.1 and 3B5.2 mAbs, suggested that the
mAbs bind to an epitope, including amino acid residues at position 162 in the HA1
protein (R162 and K162). Unexpectedly, however, when five Eurasian-origin H5 low
pathogenic AIV (LPAIV) strains with R162 were examined (EA-nonGsGD clade) as well
as two American-origin strains (Am-nonGsGD clade), the mAb recognized only EA
nonGsGD clade strains. The R162 and K162 residues in the HA1 protein were highly
conserved among 36 of the 43 H5N1 clades reported, including clades 2.3.2.1a and
2.3.2.1c that are currently circulating in Asia, Africa and Europe. The amino
acid residues (158-PTIKRSYNNTNQE-170) in the HA1 protein are probably an epitope
responsible for the cross-clade reactivity of the mAbs, considering the epitopes
reported elsewhere. The 3B5.1 and 3B5.2 mAbs may be useful for the specific
detection of H5N1 HPAIVs circulating in the field.
PMID- 28405767
TI - Erratum to: Four-year maintenance treatment with adalimumab in Japanese patients
with moderately to severely active ulcerative colitis.
PMID- 28405768
TI - Efficient isogeometric thin shell formulations for soft biological materials.
AB - This paper presents three different constitutive approaches to model thin
rotation-free shells based on the Kirchhoff-Love hypothesis. One approach is
based on numerical integration through the shell thickness while the other two
approaches do not need any numerical integration and so they are computationally
more efficient. The formulation is designed for large deformations and allows for
geometrical and material nonlinearities, which makes it very suitable for the
modeling of soft tissues. Furthermore, six different isotropic and anisotropic
material models, which are commonly used to model soft biological materials, are
examined for the three proposed constitutive approaches. Following an
isogeometric approach, NURBS-based finite elements are used for the
discretization of the shell surface. Several numerical examples are investigated
to demonstrate the capabilities of the formulation. Those include the contact
simulation during balloon angioplasty.
PMID- 28405769
TI - Study on the apoptosis mediated by cytochrome c and factors that affect the
activation of bovine longissimus muscle during postmortem aging.
AB - This study investigates whether bovine longissimus muscle cell apoptosis occurs
during postmortem aging and whether apoptosis is dependent on the mitochondria
pathway. This study also determines the apoptosis process mediated by cytochrome
c after its release from mitochondria and the factors that affect the activation
processes. Results indicate that apoptotic nuclei were detected at 12 h
postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated
the caspase-9 and caspase-3 at early postmortem aging and the activation of
caspase-9 occurs before the activation of caspase-3. The pH level decreased
during the first 48 h postmortem, whereas the mitochondria membrane permeability
increased from 6 to 12 h. Results demonstrate that an apoptosis process of bovine
muscle occurred during postmortem aging. Apoptosis was dependent on the
mitochondria pathway and occurred at early postmortem aging. Increased
mitochondria membrane permeability and low pH are necessary conditions for the
release of cytochrome c during postmortem aging.
PMID- 28405770
TI - Comparing mechanistic and empirical approaches to modeling the thermal niche of
almond.
AB - Delineating locations that are thermally viable for cultivating high-value crops
can help to guide land use planning, agronomics, and water management. Three
modeling approaches were used to identify the potential distribution and key
thermal constraints on on almond cultivation across the southwestern United
States (US), including two empirical species distribution models (SDMs)-one using
commonly used bioclimatic variables (traditional SDM) and the other using more
physiologically relevant climate variables (nontraditional SDM)-and a mechanistic
model (MM) developed using published thermal limitations from field studies.
While models showed comparable results over the majority of the domain, including
over existing croplands with high almond density, the MM suggested the greatest
potential for the geographic expansion of almond cultivation, with frost
susceptibility and insufficient heat accumulation being the primary thermal
constraints in the southwestern US. The traditional SDM over-predicted almond
suitability in locations shown by the MM to be limited by frost, whereas the
nontraditional SDM showed greater agreement with the MM in these locations,
indicating that incorporating physiologically relevant variables in SDMs can
improve predictions. Finally, opportunities for geographic expansion of almond
cultivation under current climatic conditions in the region may be limited,
suggesting that increasing production may rely on agronomical advances and
densifying current almond plantations in existing locations.
PMID- 28405771
TI - Sacral epidural arteriovenous fistulas: imitators of spinal dural arteriovenous
fistulas with different pathologic anatomy: report of three cases and review of
the literature.
AB - BACKGROUND: Sacral epidural arteriovenous fistulas (eAVFs) are rare and often
misdiagnosed because of the incongruence between the thoracic level of clinical
deficits and the sacral location of the offending pathology. Failure to diagnose
this lesion delays treatment, resulting in prolonged venous hypertension in the
cord, progressive neurological deterioration, and decreased chances of recovery.
METHODS: A single-institution case series and the published literature were
reviewed. RESULTS: Three patients had sacral eAVFs are located in the ventral
epidural space with outflow connections to radicular veins that arterialized
spinal cord veins, all presenting with thoracic myelopathy, venous engorgement,
and delayed diagnosis. All eAVFs were occluded completely with radiographic and
clinical improvement. CONCLUSIONS: Sacral eAVF pathophysiology, namely venous
hypertension and compromised spinal cord circulation, is exactly the same as
dural AVFs, as is their treatment: the interruption of outflow by occlusion of
the draining vein, which effectively eliminates venous hypertension, without
occlusion of the actual fistula itself. Epidural exposure of sacral eAVFs is not
necessary, whereas complete intradural occlusion of their radicular drainage is.
Draining radicular veins intermingle with the nerve roots and their occasional
multiplicity makes them more difficult to identify intraoperatively.
PMID- 28405772
TI - Incidence and Prognostic Value of Metastases to "Posterior" and Para-aortic Lymph
Nodes in Resectable Gastric Cancer.
AB - BACKGROUND: The purpose of this retrospective study was to evaluate the incidence
and prognostic value of metastases to "posterior" (8p, 12b/p, 13) and para-aortic
lymph nodes in a large cohort of Western patients submitted to D2 plus
lymphadenectomy. METHODS: Removal of "posterior" nodes was performed in 743
patients, and para-aortic lymphadenectomy in a subgroup of 390 patients. After
lymph node mapping and retrieval on the fresh specimen, a median number of 41
total lymph nodes were analyzed. The median follow-up period was 37 months for
the entire series and 68 months for survivors. RESULTS: Of 743 included patients,
23 (3.1%) had metastases in station 8p, 12 (1.6%) in station 12b/p, and 19 (2.6%)
in station 13. On the whole, 47 of 743 patients (6.3%) had positive "posterior"
nodes. Para-aortic metastases were present in 42 of 390 patients (10.8%).
Metastases to "posterior" stations were significantly related to depth of
invasion, number of positive nodes, and surgical radicality. Distal tumors showed
higher trend to metastasize to "posterior" nodes than upper third, whereas for
para-aortic metastases it was the reverse. 5-year survival in patients with
positivity to "posterior" nodes was 17%, with no significant difference according
to 8p, 12b/p, and 13 stations; long-term outcome was overlapping to pN3b stage. 5
year survival in para-aortic positive cases was 11%, and a trend to better
outcome was observed in proximal tumors. CONCLUSIONS: Although metastases to
"posterior" and para-aortic nodes are expression of an advanced nodal stage, not
negligible survival rates are observed in subgroups of patients.
PMID- 28405774
TI - Bacillus methylotrophicus M4-96 isolated from maize (Zea mays) rhizoplane
increases growth and auxin content in Arabidopsis thaliana via emission of
volatiles.
AB - Plant growth-promoting rhizobacteria stimulate plant growth and development via
different mechanisms. In this study, we characterized the effect of volatiles
from Bacillus methylotrophicus M4-96 isolated from the maize rhizosphere on root
and shoot development, and auxin homeostasis in Arabidopsis thaliana.
Phytostimulation occurred after 4 days of interaction between M4-96 and
Arabidopsis grown on opposite sides of divided Petri plates, as revealed by
enhanced primary root growth, root branching, leaf formation, and shoot biomass
accumulation. Analysis of indole-3-acetic acid content revealed two- and
threefold higher accumulation in the shoot and root of bacterized seedlings,
respectively, compared to uninoculated plants, which was correlated with
increased expression of the auxin response marker DR5::GUS. The auxin transport
inhibitor 1-naphthylphthalamic acid inhibited primary root growth and lateral
root formation in axenically grown seedlings and antagonized the plant growth
promoting effects of M4-96. Analysis of bacterial volatile compounds revealed the
presence of four classes of compounds, including ten ketones, eight alcohols, one
aldehyde, and two hydrocarbons. However, the abundance of ketones and alcohols
represented 88.73 and 8.05%, respectively, of all airborne signals detected, with
acetoin being the main compound produced. Application of acetoin had a different
effect from application of volatiles, suggesting that either the entire pool or
acetoin acting in concert with another unidentified compound underlies the strong
phytostimulatory response. Taken together, our results show that B.
methylotrophicus M4-96 generates bioactive volatiles that increase the active
auxin pool of plants, stimulate the growth and formation of new organs, and
reprogram root morphogenesis.
PMID- 28405773
TI - Failure and Fatigue Properties of Immature Human and Porcine Parasagittal
Bridging Veins.
AB - Tearing of the parasagittal bridging veins (BVs) is thought to be a source of
extra-axial hemorrhage (EAH) associated with abusive traumatic brain injuries
(TBIs) in children. However, the pediatric BV mechanical properties are unknown.
We subjected porcine adult, porcine newborn, and human infant BVs to either a low
rate pull to failure, a high rate pull to failure, or 30 s of cyclic loading
followed by a pull to failure. An additional subset of human infant BVs was
examined for viscoelastic recovery between two cycling episodes. We found that
human infant BVs are stronger than porcine BVs, and BV mechanical properties are
rate dependent, but not age dependent. Successive cyclic loading to a uniform
level of stretch softened BVs with decaying peak stresses, and shifted their
stress-stretch relationship. These data are critical in understanding BV tissue
behavior in accidental and abusive trauma scenarios, which in turn may clarify
circumstances that may be injurious to young children.
PMID- 28405775
TI - Iron Deficiency Treatment in Patients with Heart Failure.
AB - Iron deficiency (ID) is one of the major risk factors for disability and
mortality worldwide, and it was identified as a common and ominous comorbidity in
patients with heart failure (HF), both with and without anaemia. Based on two
clinical trials (FAIR-HF and CONFIRM-HF) and other epidemiological evidence, ID
has been recognized as an important therapeutic target in symptomatic patients
with HF and LVEF <=45%.Intravenous iron supplementation has been demonstrated to
be safe and effective for iron repletion and related with an improvement in
clinical status, exercise capacity, and quality of life. Ongoing trials are
testing the hypothesis that such a therapy may also reduce the risk of HF
hospitalizations and cardiovascular death.
PMID- 28405776
TI - Immune-Mediated and Hypoxia-Regulated Programs: Accomplices in Resistance to Anti
angiogenic Therapies.
AB - In contrast to mechanisms taking place during resistance to chemotherapies or
other targeted therapies, compensatory adaptation to angiogenesis blockade does
not imply a mutational alteration of genes encoding drug targets or multidrug
resistance mechanisms but instead involves intrinsic or acquired activation of
compensatory angiogenic pathways. In this article we highlight hypoxia-regulated
and immune-mediated mechanisms that converge in endothelial cell programs and
preserve angiogenesis in settings of vascular endothelial growth factor (VEGF)
blockade. These mechanisms involve mobilization of myeloid cell populations and
activation of cytokine- and chemokine-driven circuits operating during intrinsic
and acquired resistance to anti-angiogenic therapies. Particularly, we focus on
findings underscoring a role for galectins and glycosylated ligands in promoting
resistance to anti-VEGF therapies and discuss possible strategies to overcome or
attenuate this compensatory pathway. Finally, we highlight emerging evidence
demonstrating the interplay between immunosuppressive and pro-angiogenic programs
in the tumor microenvironment (TME) and discuss emerging combinatorial anticancer
strategies aimed at simultaneously potentiating antitumor immune responses and
counteracting aberrant angiogenesis.
PMID- 28405777
TI - How visual working memory contents influence priming of visual attention.
AB - Recent evidence shows that when the contents of visual working memory overlap
with targets and distractors in a pop-out search task, intertrial priming is
inhibited (Kristjansson, Saevarsson & Driver, Psychon Bull Rev 20(3):514-521,
2013, Experiment 2, Psychonomic Bulletin and Review). This may reflect an
interesting interaction between implicit short-term memory-thought to underlie
intertrial priming-and explicit visual working memory. Evidence from a non-pop
out search task suggests that it may specifically be holding distractors in
visual working memory that disrupts intertrial priming (Cunningham & Egeth,
Psychol Sci 27(4):476-485, 2016, Experiment 2, Psychological Science). We
examined whether the inhibition of priming depends on whether feature values in
visual working memory overlap with targets or distractors in the pop-out search,
and we found that the inhibition of priming resulted from holding distractors in
visual working memory. These results are consistent with separate mechanisms of
target and distractor effects in intertrial priming, and support the notion that
the impact of implicit short-term memory and explicit visual working memory can
interact when each provides conflicting attentional signals.
PMID- 28405778
TI - Verification and fine mapping of qGW1.05, a major QTL for grain weight in maize
(Zea mays L.).
AB - Grain weight, one of the important factors to determine corn yield, is a typical
quantitative inheritance trait. However, the molecular genetic basis of grain
weight still remains limited. In our previous researches, a major QTL associated
with grain weight, qGW1.05, has been identified between SSR markers umc1601 and
umc1754 at bin locus 1.05-1.06 in maize. Here, its genetic and environmental
stabiliteis were verified using a BC3F2 population to identify the effect of
qGW1.05 on grain weight. Further, qGW1.05-NILs were obtained by MAS successfully.
Via a large BC6F2 segregation population, together with polymorphic
microsatellite markers developed between the parents to screen the genotype of
the recombinant plants, qGW1.05 was positioned to a 1.11 Mb genome interval.
Furthermore, the progenies of 15 recombinants were tested to confirm the effect
of qGW1.05 on grain weight. Combining collinearity among cereal crops and genome
annotation, the several candidate genes taking part in grain development were
identified in the qGW1.05 region. In this study, qGW1.05 was limited to a 1.11 Mb
region on chromosome 1, which established the foundation for understanding the
molecular basis underlying kernel development and improving grain weight through
MAS using the tightly flanking molecular markers in maize.
PMID- 28405779
TI - Multidirectional inhibition of cortico-hippocampal neurodegeneration by kolaviron
treatment in rats.
AB - Earliest signs of neurodegenerative cascades in the course of Alzheimer's disease
(AD) are seen within the prefrontal cortex (PFC) and hippocampus, with
pathological evidences in both cortical structures correlating with manifestation
of behavioural and cognitive deficits. Despite the enormous problems associated
with AD's clinical manifestations in sufferers, therapeutic advances for the
disorder are still very limited. Therefore, this study examined cortico
hippocampal microstructures in models of AD, and evaluated the possible
beneficial roles of kolaviron (Kv)-a biflavonoid complex in rats. Nine groups of
rats were orally exposed to sodium azide (NaN3) or aluminium chloride (AlCl3)
solely or in different combinations with Kv. Sequel to sacrifice and transcardial
perfusion (using buffered saline then 4% paraformaldehyde), PFC and hippocampal
tissues were harvested and processed for: spectrophotometric assays of oxidative
stress and neuronal bioenergetics parameters, histological demonstration of
cytoarchitecture and immunohistochemical evaluation of astrocytes and neuronal
cytoskeleton. Results showed alterations in mitochondrial functions, which led to
compromised neuronal antioxidant system, dysfunctional neural bioenergetics,
hypertrophic astrogliosis, cytoskeletal dysregulation and neuronal death within
the PFC and hippocampus. These degenerative events were associated with NaN3 and
AlCl3 toxicity in rats. Furthermore, Kv inhibited cortico-hippocampal
degeneration through multiple mechanisms that primarily involved halting of
biochemical cascades that activate proteases which destroy molecules expedient
for cell survival, and others that mediate a program of cell suicide in neuronal
apoptosis. In conclusion, Kv showed important neuroprotective roles within
cortico-hippocampal cells through multiple mechanisms, and particularly has
prominent prophylactic activity than regenerative potentials.
PMID- 28405780
TI - Psychometric validation of the dysmenorrhea daily diary (DysDD): a patient
reported outcome for dysmenorrhea.
AB - PURPOSE: The objective of this study was to evaluate the psychometric properties
of the Dysmenorrhea Daily Diary (DysDD), an electronic patient-reported outcome,
in a sample of 355 women with primary dysmenorrhea enrolled in a phase IIb,
multicenter, randomized, partially blinded, placebo-controlled trial for
treatment of dysmenorrhea. METHODS: Subjects completed the DysDD over three
menstrual cycles, one pre-treatment baseline cycle and two treatment cycles. The
DysDD was administered alongside the Menstrual Distress Questionnaire (MDQ), the
Short-Form 36 Version 2.0 (SF-36v2), and a Global Assessment of Change (GAC).
Item response distributions, test-retest reliability, concurrent and known groups
validity, responsiveness, and minimally important difference (MID) were evaluated
for the DysDD. RESULTS: As expected, item response distributions varied
throughout the menstrual period for all items, with the response scales fully
utilized. Within-cycle test-retest reliability was adequate (weighted kappa: 0.5
0.7), although between-cycle test-retest was poor (weighted kappa: 0.1-0.5), most
likely due to the highly variable nature of dysmenorrhea between cycles rather
than limitations of the measure. Correlations with the MDQ and SF-36v2 were low
moderate, but in the predicted direction, supporting concurrent validity. There
were significant differences in DysDD scores across severity groups based on pain
medication use. The DysDD was responsive to changes in patients' dysmenorrhea
with significantly different changes in scores between change groups (p <
0.0001). MID analyses suggest changes on the DysDD 0-10 pelvic pain score of
three points can be considered clinically meaningful. CONCLUSIONS: Overall,
findings indicate that the DysDD has acceptable reliability and is a valid and
responsive instrument for assessing dysmenorrhea.
PMID- 28405781
TI - Universal screening for microsatellite instability in colorectal cancer in the
clinical genomics era: new recommendations, methods, and considerations.
PMID- 28405782
TI - Importance of updating family cancer history in childhood cancer survivors.
AB - Estimates of the number of childhood cancers with a genetic basis range from 5
8.5% found in germline samples to 29% based on clinical criteria. Family history
taking practice is a fundamental first step in detecting at risk individuals and
families. This study focused on Li-Fraumeni Syndrome (LFS), a highly penetrant
cancer syndrome. Reported family history in a cohort of 648 of cancer survivor
cohort (CCS) was examined. Eligible CCS were: (i) aged up to 14 years at
diagnosis; (ii) more than 5 years postdiagnosis; (iii) treated for a childhood
cancer at the study hospitals in NSW, Australia; (iv) in remission for more than
3 years. CCS completed self-administered questionnaires. Medical records
confirmed diagnosis and treatment-related information. Our findings reveal an
increased cancer risk among sibling and relatives of CCS. 91% of siblings
diagnosed with cancer were diagnosed under the age of 40 and about 30% diagnosed
under the aged of 15 revealing a 5- (RR = 5.1; 95% CI, 3.3-7.9) and 44-fold (RR =
44.6; 95% CI, 18.4-108.3) increased risked of cancer compared with the Australian
population, respectively. About 2% of CCS reported that they had been diagnosed
with a genetic cancer syndrome. However, 11% of survivors described a family
history pattern which met Chompret criteria for screening for TP53 mutations
associated with LFS. Our data suggests that familial cancer predispositions may
be initially overlooked. Aperiodic and accurate ascertainment of family cancer
history of childhood cancer patients and survivors is therefore recommended.
PMID- 28405783
TI - How do clinical genetics consent forms address the familial approach to
confidentiality and incidental findings? A mixed-methods study.
AB - Genetic test results can be relevant to patients and their relatives. Questions
thus arise around whether clinicians regard genetic information as confidential
to individuals or to families, and about how they broach this and other issues,
including the potential for incidental findings, in consent (forms) for genetic
testing. We conducted a content analysis of UK-wide genetic testing consent forms
and interviewed 128 clinicians/laboratory scientists. We found that almost all
genetic services offered patients multiple, sometimes unworkable, choices on
forms, including an option to veto the use of familial genetic information to
benefit relatives. Participants worried that documented choices were overriding
professional judgement and cautioned against any future forms dictating practice
around incidental findings. We conclude that 'tick-box' forms, which do little to
enhance autonomy, are masking valid consent processes in clinical practice. As
genome-wide testing becomes commonplace, we must re-consider consent processes,
so that they protects patients'-and relatives'-interests.
PMID- 28405785
TI - Determination of the potential implementation impact of 2016 ministry of
environmental protection generic assessment criteria for potentially contaminated
sites in China.
AB - The Ministry of Environmental Protection of China issued a 3rd draft edition of
risk-based Generic Assessment Criteria (the MEP-GAC) in March 2016. Since these
will be the first authoritative GAC in China, their implementation is likely to
have a significant impact on China's growing contaminated land management sector.
This study aims to determine the potential implementation impact of the MEP-GAC
through an in-depth analysis of the management context, land use scenarios,
health criteria values adopted and exposure pathways considered. The MEP-GAC have
been proposed for two broad categories of land use scenarios for contaminated
land risk assessment, and these two categories of land use scenarios need to be
further delved, and a MEP-GAC for Chinese cultivated land scenario ought to be
developed, to ensure human health protection of Chinese farmers. The MEP-GAC have
adopted 10-6 as the acceptable lifetime cancer risk, given the widespread extent
and severe level of land contamination in China, consideration should be given to
the decision on excess lifetime cancer risk of 10-5. During risk assessment
process in practice, it is better to review the 20% TDI against local
circumstances to determine their suitability before adopting it. The MEP-GAC are
based on a SOM value of 1%, for regions with particularly high SOM, it might be
necessary to develop regional GAC, due to SOM's significant impact on the GAC
developed. An authoritative risk assessment model developed based on HJ25.3-2014
would help facilitate the DQRA process in practice. The MEP-GAC could better
reflect the likely exposures of China's citizens due to vapour inhalation by
using characteristics of Chinese exposure scenarios, including China-generic
building stock, as inputs into the Johnson and Ettinger model as opposed to
adoption of the US EPA parameters. The MEP-GAC once implemented will set the
trajectory for the development of the investigation, assessment and remediation
of land contamination for years.
PMID- 28405784
TI - Genomic and functional characterization of coleopteran insect-specific alpha
amylase inhibitor gene from Amaranthus species.
AB - The smallest 32 amino acid alpha-amylase inhibitor from Amaranthus
hypochondriacus (AAI) is reported. The complete gene of pre-protein (AhAI)
encoding a 26 amino acid (aa) signal peptide followed by the 43 aa region and the
previously identified 32 aa peptide was cloned successfully. Three cysteine
residues and one disulfide bond conserved within known alpha-amylase inhibitors
were present in AhAI. Identical genomic and open reading frame was found to be
present in close relatives of A. hypochondriacus namely Amaranthus paniculatus,
Achyranthes aspera and Celosia argentea. Interestingly, the 3'UTR of AhAI varied
in these species. The highest expression of AhAI was observed in A.
hypochondriacus inflorescence; however, it was not detected in the seed. We
hypothesized that the inhibitor expressed in leaves and inflorescence might be
transported to the seeds. Sub-cellular localization studies clearly indicated the
involvement of AhAI signal peptide in extracellular secretion. Full length rAhAI
showed differential inhibition against alpha-amylases from human, insects, fungi
and bacteria. Particularly, alpha-amylases from Helicoverpa armigera
(Lepidoptera) were not inhibited by AhAI while Tribolium castaneum and
Callosobruchus chinensis (Coleoptera) alpha-amylases were completely inhibited.
Molecular docking of AhAI revealed tighter interactions with active site residues
of T. castaneum alpha-amylase compared to C. chinensis alpha-amylase, which could
be the rationale behind the disparity in their IC50. Normal growth, development
and adult emergence of C. chinensis were hampered after feeding on rAhAI.
Altogether, the ability of AhAI to affect the growth of C. chinensis demonstrated
its potential as an efficient bio-control agent, especially against stored grain
pests.
PMID- 28405786
TI - Maternal Responsiveness as a Predictor of Self-Regulation Development and
Attention-Deficit/Hyperactivity Symptoms Across Preschool Ages.
AB - Preschool-age "hot" executive function capacity (i.e. reward-related effortful
control) represents an early kind of self-regulation that is involved in social
adjustment development as well as the development of subtypes of attention
deficit/hyperactivity disorder (ADHD). Early self-regulation development might be
malleable by responsive parenting. We analyzed whether maternal
responsiveness/sensitivity predicts reward-related control (RRC) development
within the preschool period, and whether RRC mediates a negative link between
maternal responsiveness and ADHD symptoms. A sample of 125 preschoolers and their
families were seen at the ages of 4 and 5 years. Maternal
responsiveness/sensitivity was assessed via home observations, RRC by
neuropsychological tasks, and ADHD symptoms by a structured clinical parent
interview. Maternal responsiveness/sensitivity predicted RRC development. The
negative link between maternal responsiveness/sensitivity at 4 years and ADHD
symptoms at 5 years was mediated by RRC performance at 5 years. Preschoolers
showing ADHD symptoms combined with low RRC capacity in particular might benefit
from responsive/sensitive parenting.
PMID- 28405787
TI - Outcomes of switching treatment to aflibercept in patients with macular oedema
secondary to central retinal vein occlusion refractory to ranibizumab.
AB - PURPOSE: To assess the treatment outcome of switching from ranibizumab to
aflibercept intravitreal injections in patients with macular oedema secondary to
central retinal vein occlusion (CRVO). METHODS: A prospective interventional
study was conducted in a tertiary retina service in Leicester Royal Infirmary,
UK, where patients with CRVO and associated macular oedema were recruited. First
line treatment involved three monthly ranibizumab injections. Non-responders were
defined as patients who despite a minimum of three consecutive injections had
persistent intraretinal fluid one month after the last injection. In these cases,
a treatment change to aflibercept injections on a per-needed basis was decided.
Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were
measured before and after switching of treatment. Follow-up period lasted for a
minimum of 24 weeks after switching. RESULTS: Twenty-nine eyes of 29 patients
with refractory macular oedema secondary to CRVO were included. All eyes had an
average of 4.5 ranibizumab intravitreal injections in a mean period of 6 months
without reduction in intraretinal fluid and/or no visual acuity gain. A
significant decrease in mean CRT from 633.67 +/- 242.42 to 234.62 +/- 78.28 MUm
and improvement in mean BCVA from 1.34 +/- 0.66 log MAR to 0.91 +/- 0.73 log MAR
were noticed after switching treatment to aflibercept. The average number of
aflibercept injections needed for oedema resolution was 2.19. CONCLUSIONS:
Aflibercept is an effective alternative treatment for macular oedema secondary to
CRVO refractory to ranibizumab. Good anatomical and functional result can be
achieved with few injections. The maintenance of these results after 6 months is
yet to be investigated.
PMID- 28405788
TI - Electroneuromyographic findings in pseudoexfoliation syndrome.
AB - PURPOSE: To examine peripheral electroneuromyographic findings in patients with
ocular pseudoexfoliation syndrome (PEX) and to compare them controls without PEX.
METHODS: A case-control study design was used to examine 31 patients with PEX and
compare the findings with those of 31 age- and sex-matched healthy controls. All
patients underwent complete ophthalmologic examination that included peripheral
electroneuromyography examination. Motor and sensorial nerve conduction of the
median, ulnar, tibial, peroneal, and sural nerve and the sympathetic skin
response were measured. RESULTS: The average sensorial nerve latency of the ulnar
and sural nerve was significantly longer in the PEX group compared to the control
group (p < 0.05). The average sensorial nerve conduction amplitude and the
velocity of the ulnar and sural nerve were significantly lower in the PEX group
(p < 0.05). DISCUSSION: Peripheral nerves, especially sensorial fibers, appear to
be affected in PEX patients. These finding may indicate that PEX is a systemic
disease.
PMID- 28405791
TI - The Ethics of Technology for Population Health.
PMID- 28405789
TI - Left ventricular strain and twisting in heart failure with preserved ejection
fraction: an updated review.
AB - Despite the high prevalence of the patients with heart failure with preserved
ejection fraction (HFpEF), our knowledge about this entity, from diagnostic tools
to therapeutic approach, is still not well established. The evaluation of
patients with HFpEF is mainly based on echocardiography, as the most widely
accepted tool in cardiac imaging. Identification of left ventricular (LV)
diastolic dysfunction has long been considered as the only responsible for HFpEF,
and its evaluation is still "sine qua non" of HFpEF diagnostics. However, one
should be aware of the fact that identifying cardiac dysfunction in HFpEF might
be very challenging and often needs more complex evaluation of cardiac structure
and function. New echocardiographic modalities such as 2D and 3D speckle tracking
imaging could help in the diagnosis of HFpEF and provide further information
regarding LV function and mechanics. Early diagnosis, medical management, and
adequate monitoring of HFpEF patients are prerequisites of modern medical
treatment. New healthcare approaches require individualized patient care, which
is why clinicians should have all clinical, laboratory, and diagnostic data
before making final decisions about the treatment of any patients. This is
particularly important for HFpEF that often remains undiagnosed for quite a long
time, which further prolongs the beginning of adequate treatment and brings into
question outcome of these patients. The aim of this article is to provide the
overview of the main principles of LV mechanics and summarize recent data
regarding LV strain in patients with HFpEF.
PMID- 28405792
TI - Capsule Commentary on Egloff et al., Publication Rates of Abstracts Presented at
the Society of General Internal Medicine Annual Meeting.
PMID- 28405793
TI - Capsule Commentary on Saloner et al., Price Transparency in Primary Care: Can
Patients Learn About Costs When Scheduling an Appointment?
PMID- 28405794
TI - A Model for the Spread of an Invasive Weed, Tradescantia fluminensis.
AB - Tradescantia fluminensis is an invasive weed and a serious threat to native
forests in eastern Australia and New Zealand. Current methods of eradication are
often ineffective, so understanding the growth mechanisms of Tradescantia is
important in formulating better control strategies. We present a partial
differential equation (PDE) model for Tradescantia growth and spatial
proliferation that accounts for Tradescantia's particular creeping and branching
morphology, and the impact of self-shading on plant growth. This is the first PDE
model to represent a weed that spreads via a creeping growth habit rather than by
seed dispersal. We use a travelling wave analysis to investigate how Tradescantia
extends to colonise new territory. Numerical simulations and analysis show that
the model provides a good qualitative representation of the behaviour of this
plant. This model provides a foundation for assessing different control and
eradication strategies for Tradescantia.
PMID- 28405790
TI - CSH guidelines for the diagnosis and treatment of drug-induced liver injury.
AB - Drug-induced liver injury (DILI) is an important clinical problem, which has
received more attention in recent decades. It can be induced by small chemical
molecules, biological agents, traditional Chinese medicines (TCM), natural
medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic
DILI is far more common than intrinsic DILI clinically and can be classified into
hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed
injury, and vascular injury based on the types of injured target cells. The CSH
guidelines summarized the epidemiology, pathogenesis, pathology, and clinical
manifestation and gives 16 evidence-based recommendations on diagnosis,
differential diagnosis, treatment, and prevention of DILI.
PMID- 28405795
TI - Erratum to: Acidic domains differentially read histone H3 lysine 4 methylation
status and are widely present in chromatin-associated proteins.
PMID- 28405796
TI - Antiphospholipid antibodies: crossroads between autoimmunity and infections?
PMID- 28405801
TI - Urine exosomes from healthy and hypertensive pregnancies display elevated level
of alpha-subunit and cleaved alpha- and gamma-subunits of the epithelial sodium
channel-ENaC.
AB - Preeclampsia is characterized by hypertension, proteinuria, suppression of plasma
renin-angiotensin-aldosterone, and impaired urine sodium excretion. Aberrantly
filtered plasmin in urine may activate proteolytically the gamma-subunit of the
epithelial sodium channel (ENaC) and promote Na+ reabsorption and urine K+ loss.
Plasma and urine was sampled from patients with preeclampsia, healthy pregnant
controls and non-pregnant women, and from patients with nephrostomy catheters.
Aldosterone concentration, urine plasminogen, and protein were determined.
Exosomes were isolated by ultracentrifugation. Immunoblotting was used to detect
exosome markers; gamma-ENaC (two different epitopes within the inhibitory peptide
tract), alpha-ENaC, and renal outer medullary K-channel (ROMK) and compared with
human kidney cortex homogenate. Urine total plasmin(ogen) was significantly
increased in preeclampsia, plasma and urine aldosterone was higher in pregnancy
compared to non-pregnancy, and the urine Na/K ratio was lower in preeclampsia
compared to healthy pregnancy. Exosome markers ALIX and AQP-2 were stably
associated with exosomes across groups. Exosomal alpha-ENaC-subunit migrated at
75 kDa and dominantly at 50 kDa and was significantly elevated in pregnancy. In
human kidney cortex tissue and two of four pelvis catheter urine, ~90-100 kDa
full-length gamma-ENaC was detected while no full-length gamma-ENaC but 75, 60,
and 37 kDa variants dominated in voided urine exosomes. There was no difference
in gamma-ENaC protein abundances between healthy pregnancy and preeclampsia. ROMK
was detected inconsistently in urine exosomes. Pregnancy and preeclampsia were
associated with increased abundance of furin-cleaved alpha-ENaC subunit while
gamma-subunit appeared predominantly in cleaved form independently of conditions
and with a significant contribution from post-renal cleavage.
PMID- 28405802
TI - Vasculo-protective effect of BMS-309403 is independent of its specific inhibition
of fatty acid-binding protein 4.
AB - Fatty acid-binding protein (FABP) 4 is an adipocytokine mainly expressed in
adipocyte and macrophage. Blood FABP4 is related not only to metabolic disorders
including insulin resistance and atherosclerosis but also increased blood
pressure. We tested the hypothesis that FABP4 plays roles in pathogenesis of
hypertension development including proliferation, migration, and inflammation of
vascular smooth muscle cells (SMCs) as well as contractile reactivity. FABP4
alone had no influence on proliferation, migration, and inflammation of rat
mesenteric arterial SMCs, while it significantly enhanced smooth muscle
contraction and increases of systolic blood pressure (SBP) induced by
noradrenaline (NA). BMS-309403, an FABP4 inhibitor, significantly inhibited
platelet-derived growth factor-BB-induced DNA synthesis and migration via
preventing p38 and HSP27 activation. Further, BMS-309403 significantly inhibited
tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule
1 and monocyte chemotactic protein-1 as well as monocyte adhesion via preventing
NF-kappaB activation. Interestingly, SMCs do not express FABP4. Long-term
treatment of spontaneously hypertensive rats (SHR) with BMS-309403 significantly
inhibited impaired relaxation in isolated mesenteric arteries and left
ventricular hypertrophy, while it had no influence on SBP. We for the first time
showed that FABP4 acutely enhances NA-induced increases of SBP possibly through
the enhancement of peripheral arterial contractility. BMS-309403 prevents
proliferation, migration, and inflammatory responses of SMCs, although exogenous
application of FABP4 has no influence on the cellular responses. Furthermore, we
demonstrated that long-term treatment with BMS-309403 partially improves the
pathological conditions of SHR. These results indicate that BMS-309403 would be
useful for developing a new pharmacotherapeutic agent against obesity-associated
hypertension and complications.
PMID- 28405803
TI - miR-15a-5p, A Novel Prognostic Biomarker, Predicting Recurrent Colorectal
Adenocarcinoma.
AB - INTRODUCTION: Colorectal cancer is one of the most common gastrointestinal
diseases and the second leading cause of cancer-associated deaths among adults.
miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a
transcription factor essential for prolonged cancer cell proliferation and
survival. In the current study, we assessed the potential diagnostic and
prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma.
METHODS: To accomplish this goal, total RNA was extracted from 182 colorectal
adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After
polyadenylation by poly(A) polymerase and subsequent reverse transcription with
an oligo-dT adapter primer, miR-15a-5p expression was analyzed using an in-house
developed reverse transcription quantitative real-time PCR method, based on SYBR
Green chemistry. SNORD43 (RNU43) was used as an internal control gene. RESULTS:
miR-15a-5p was significantly upregulated in colorectal tumors compared to non
cancerous colorectal mucosae, while ROC analysis suggested its potential use for
diagnostic purposes. Moreover, miR-15a-5p overexpression predicts poor disease
free survival (DFS) and overall survival (OS). Multivariate Cox regression
analysis confirmed that miR-15a-5p overexpression is a significant unfavorable
prognosticator of DFS in colorectal adenocarcinoma, independent of other
established prognostic factors plus treatment of patients. Importantly, miR-15a
5p overexpression retains its unfavorable prognostic value in patients with T3
colorectal adenocarcinoma and in those without distant metastasis (M0). More
importantly, the cumulative DFS probability of patients with early stage disease
was significantly lower for those with colorectal adenocarcinoma overexpressing
miR-15a-5p. DISCUSSION: In conclusion, elevated expression of the cancer
associated miR-15a-5p predicts poor DFS and OS of colorectal adenocarcinoma
patients. The prognostic value of miR-15a-5p expression regarding DFS is
independent of clinicopathological factors currently used for colorectal
adenocarcinoma prognosis.
PMID- 28405804
TI - Cytoprotective Drug-Tissue Plasminogen Activator Protease Interaction Assays:
Screening of Two Novel Cytoprotective Chromones.
AB - Tissue plasminogen activator (tPA) is currently used in combination with
endovascular procedures to enhance recanalization and cerebral reperfusion and is
also currently administered as standard-of-care thrombolytic therapy to patients
within 3-4.5 h of an ischemic stroke. Since tPA is not neuroprotective or
cytoprotective, adjuvant therapy with a neuroprotective or an optimized
cytoprotective compound is required to provide the best care to stroke victims to
maximally promote clinical recovery. In this article, we describe the use of a
sensitive standardized protease assay with CH3SO2-D-hexahydrotyrosine-Gly-Arg-p
nitroanilide*AcOH, a chromogenic protease substrate that is cleaved to 4
nitroaniline (p-nitroaniline) and measured spectrophotometrically at 405 nm
(OD405 nm), and how the assay can be used as an effective screening assay to
study drug-tPA interactions. While we focus on two compounds of interest in our
drug development pipeline, the assay is broadly applicable to all small molecule
neuroprotective or cytoprotective compounds currently being discovered and
developed worldwide. In this present study, we found that the specific tPA
inhibitor, plasminogen activator inhibitor-1 (PAI-1; 0.25 MUM), significantly (p
< 0.0001) inhibited 4-nitroaniline release, by 97.74% during the 10-min duration
of the assay, which is indicative of tPA protease inhibition. In addition, two
lead chromone cytoprotective candidates, 2-(3',4',5'-trihydroxyphenyl)chromen-4
one (3',4',5'-trihydroxyflavone) (CSMC-19) and 3-hydroxy-2-[3-hydroxy-4
(pyrrolidin-1-yl)phenyl]benzo[h]chromen-4-one (CSMC-140), also significantly (p <
0.05) reduced 4-nitroaniline accumulation, but to a lesser extent. The reduction
was 68 and 45%, respectively, at 10 MUM, and extrapolated IC50 values were 4.37
and >10 MUM for CSMC-19 and CSMC-140, respectively. Using bonafide 4
nitroaniline, we then demonstrated that the reduction of 4-nitroaniline detection
was not due to drug-4-nitroaniline quenching of signal detection at OD405 nm. In
conclusion, the results suggest that high concentrations of both cytoprotectives
reduced 4-nitroaniline production in vitro, but the inhibition only occurs with
concentrations 104-1025-fold that of EC50 values in an efficacy assay. Thus, CSMC
19 and CSMC-140 should be further developed and evaluated in embolic stroke
models in the absence or presence of a thrombolytic. If necessary, they could be
administered once effective tPA thrombolysis has been confirmed to avoid the
possibility that the chromone will reduce the efficacy of tPA in patients. Stroke
investigator developing new cytoprotective small molecules should consider adding
this sensitive assay to their development and screening repertoire to assess
possible drug-tPA interactions in vitro as a de-risking step.
PMID- 28405805
TI - A rotating cerium anode X-ray system allows visualization of intramural coronary
vessels after cardiac stem cell therapy for myocardial infarction.
AB - Conventional angiography is insufficient for evaluating the therapeutic effect of
cardiac regeneration therapy. A microangiographic X-ray system using a cerium
anode was developed. Cerium has a characteristic X-ray with a peak at 34.6 keV,
which allows visualization of tiny amounts of iodine. The performance of the
cerium anode X-ray system was evaluated in two excised normal canine hearts and
in excised ischemic canine hearts treated with c-kit-positive cardiac stem cells
(5 canines) or without cells (5 control canines). In the normal canines, branches
penetrating from the left anterior descending artery into the myocardium were
visualized, down to third-order branches. In just the treated hearts treated with
stem cells, small vessels characterized by irregular vessel walls were observed.
The cerium anode X-ray system allowed visualization of microvessels in excised
ischemic canine hearts, and may evaluate the effect of cardiac stem cell therapy.
PMID- 28405806
TI - Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in
regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.
AB - The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at
juxtaparanodal (JXP) regions are essential in the regulation of nerve
excitability and play a critical role in axonal conduction. When demyelination
occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly
to the equilibrium potential of K+, which results in an axonal conduction
blockade. The recovery of K+-dependent communication signals and proper
clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve
regeneration following peripheral nerve injury. However, little is known about
potassium channel expression and its relationship with the dynamic potassium ion
distribution at the node of Ranvier during the regenerative process of peripheral
nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was
performed using an in vivo model of PNI. The distribution of K+ at regenerating
axons following EEN was detected by time-of-flight secondary-ion mass
spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels
were examined by confocal microscopy and western blotting. Our data showed that
the re-establishment of K+ distribution and intensity was correlated with the
functional recovery of compound muscle action potential morphology in EEN rats.
Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at
the nodal region of the regenerating nerve corresponded to changes in the K+
distribution. This study provided direct evidence of K+ distribution in
regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels
re-clustered at the JXP regions of regenerating axons are essential for
modulating the proper patterns of K+ distribution in axons for maintaining
membrane potential stability after EEN.
PMID- 28405807
TI - Management and Outcomes of Acute Surgical Patients at a District Hospital in
Uganda with Non-physician Emergency Clinicians.
AB - INTRODUCTION: Acute surgical care services in rural Sub-Saharan Africa suffer
from human resource and systemic constraints. Developing emergency care systems
and task sharing aspects of acute surgical care addresses many of these issues.
This paper investigates the degree to which specialized non-physicians practicing
in a dedicated Emergency Department contribute to the effective and efficient
management of acute surgical patients. METHODS: This is a retrospective review of
an electronic quality assurance database of patients presenting to an Emergency
Department in rural Uganda staffed by non-physician clinicians trained in
emergency care. Relevant de-identified clinical data on patients admitted
directly to the operating theater from 2011 to 2014 were analyzed in Microsoft
Excel. RESULTS: Overall, 112 Emergency Department patients were included in the
analysis and 96% received some form of laboratory testing, imaging, medication,
or procedure in the ED, prior to surgery. 72% of surgical patients referred by ED
received preoperative antibiotics, and preoperative fluid resuscitation was
initiated in 65%. Disposition to operating theater was accomplished within 3 h of
presentation for 73% of patients. 79% were successfully followed up to assess
outcomes at 72 h. 92% of those with successful follow-up reported improvement in
their clinical condition. The confirmed mortality rate was 5%. CONCLUSION:
Specialized non-physician clinicians practicing in a dedicated Emergency
Department can perform resuscitation, bedside imaging and laboratory studies to
aid in diagnosis of acute surgical patients and arrange transfer to an operating
theater in an efficient fashion. This model has the potential to sustainably
address structural and human resources problems inherent to Sub-Saharan Africa's
current acute surgical care model and will benefit from further study and
expansion.
PMID- 28405808
TI - Staphylococcus lugdunensis: a neglected pathogen of infections involving fracture
fixation devices.
AB - PURPOSE: Cases of fracture-fixation device infection involving Staphylococcus
lugdunensis are not frequent. The clinical characteristics and the choice of
treatment strategies of these infections are not obviously known to date.
METHODS: We performed a review of fracture-fixation device infection involving S.
lugdunensis managed by our centres. RESULTS: Among the 38 cases of fracture
fixation device infection involving S. lugdunensis, 53% were located in the
tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which
occurred in 79% of cases, was the most frequent clinical symptom, followed by
pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe
sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were
treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%)
were treated with a combination of surgery with antimicrobial therapy including
surgical debridement, antibiotics and osteosynthesis device retention in six
cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length
of antibiotic treatment was 119 days. The relapse rate was high that was not
related to selection of resistant strains. Polymicrobial infection had no impact
on clinical outcome. A combination of surgery with antimicrobial therapy was
identified as a significant prognostic factor associated with remission (p =
0.042). CONCLUSIONS: S. lugdunensis is probably involved in more infections than
has been reported. Using appropriate microbiological methods laboratories should
routinely identify the species of all coagulase-negative Staphylococci isolates
involved in fracture-fixation device infection to better achieve the treatment
strategies of fracture-fixation device infection involving S. lugdunensis.
PMID- 28405809
TI - Measurement considerations on examiner-dependent factors in the ultrasound
assessment of developmental dysplasia of the hip.
AB - PURPOSE: The standardized sonographic hip screening according to Graf has
increased reliability and comparability of measurements in the screening of
developmental dysplasia of the hip (DDH). However, examiner dependent factors
have been discussed to influence sonographic measurements. The objectives of this
study were to examine the tolerance of the transducer positioning and to analyse
the impact of transducer inclinations on Graf's hip grading system. MATERIALS AND
METHODS: Twenty-four hips in consecutive newborns were screened sonographically
in combination with an optoelectronic motion capture system to trace transducer
positions in space. Subsequently five defined inclinations of the transducer
relative to Graf's neutral transducer position were analysed, giving a total of
144 sonographic images. RESULTS: We found a permissible transducer inclination in
the axial plane of 8.8 degrees to anterior and 8.1 degrees to posterior. In the
frontal plane we found a permissible inclination of 15.4 degrees to caudal and
7.2 degrees to cranial. The impact on the alpha-angle was significant for
posterior-cranial (p < 0.001), cranial (p = 0.009), and caudal (p < 0.001)
inclined transducer positions. The effect on the results according to Graf's
grading system was significant for the caudal inclination of the transducer
position (p < 0.001). CONCLUSION: Our findings show that the standardized plane
defined by Graf's criteria allows notable inclinations of the transducer
positions. Transducer inclinations show an impact on measurement results, which
are clinically relevant. Those effects cannot be ruled out using Graf's
ultrasound criteria alone. The examiner should pay attention to avoid transducer
inclinations in the frontal plane and a combination of posterior and cranial
inclination.
PMID- 28405810
TI - What is the most reproducible classification system to assess tibial plateau
fractures?
AB - PURPOSE: Traditional classification systems for tibial plateau fractures (TPF)
are based on simple radiographs, and intra- and inter-observer variability is
low. The aim was to assess intra- and inter-observer variability using
traditional systems and some recently described classification systems of TPF in
the interpretation of standard radiographs and bidimensional (2D) and
tridimensional (3D) computed tomography (CT). METHODS: We studied all patients at
two centres who underwent TPF surgery over a three-year period. Demographic data
(age, sex, BMI) and mechanism of injury were recorded. Four observers classified
each TPF according to the Schatzker, AO, Luo, modified Duparc and Khan
classification systems. We calculated intra- and inter-observer variability using
the Kappa test. RESULTS: A total of 112 (71 males) patients were included. Mean
age was 47.1 years (range 21-86) and mean BMI was 25.2 +/- 3.6. Intra- and inter
observer variability was 0.95 and 0.62 for AO, 0.87 and 0.65 for Schaztker, 0.86
and 0.73 for Luo, 0.56 and 0.37 for the modified Duparc, and 0.43 and 0.25 for
Khan classifications. CONCLUSIONS: Although previous training could be needed,
AO, Schatzker and Luo classifications showed a good reproducibility of TPF
assessment from a combination of standard radiographs and 2D and 3D CT images.
The results using the Modified Duparc and Khan classifications were less
favourable and their use is not therefore recommended.
PMID- 28405811
TI - Advanced glycation end products as a biomarker for incisional hernia.
AB - BACKGROUND: Incisional hernia is one of the most frequent complications after
abdominal surgery, with incidences up to 30%. A reliable biomarker for the
prediction of this complication is lacking. Advanced glycosylation end products
(AGEs), also known as non-enzymatic collagen crosslinks, are correlated with
aging, smoking, hyperglycemia, hyperlipidemia and oxidative stress. In this study
the accumulation of AGEs and the relation between AGEs and incisional hernia were
investigated. MATERIALS AND METHODS: In an exploratory case-control study, 23
patients with incisional hernia after midline incision were compared with 17
patients without clinical or radiological signs of incisional hernia after
midline incision, AGEs were measured using a Skin Auto Fluorescence (SAF)-reader.
RESULTS: Twenty-three patients with a clinically significant incisional hernia
and 17 control patients were included. The study groups had significant
differences in mean BMI. There was a significant difference between mean AGEs in
patients with and without incisional hernia after midline incision (3.00 +/- 0.15
vs. 2.56 +/- 0.11, T test p = 0.03). CONCLUSION: AGE accumulation measured in the
skin indirectly with autofluorescence might be associated with incisional hernia.
Prospective larger trials should confirm this finding.
PMID- 28405813
TI - Estimation of dietary total antioxidant capacity of Korean adults.
AB - PURPOSE: Dietary total antioxidant capacity (TAC) has been reported to be
inversely associated with the risk of chronic diseases. However, little is known
about dietary TAC among the Korean population. Therefore, we aimed to estimate
the dietary TAC of Korean adults and to document the major food sources. METHODS:
We studied 33,581 Korean adults aged >=19 years who participated in the Korea
National Health and Nutrition Examination Survey 2007-2012. Dietary TAC was
estimated from 1-day 24-h dietary recall data using a TAC database comprising
antioxidant capacities of 42 dietary antioxidants, developed for common Korean
foods. RESULTS: The average dietary TAC of Korean adults was 384.7 mg VCE/d, and
the major contributors were flavonoids, followed by vitamin C and E. The energy
adjusted daily TAC level was higher in women, middle-aged adults, non-regular
alcohol consumers, current non-smokers, supplement users, and in those with a
higher income and education level than in their counterparts (P < 0.001). Fruits
(47.3%), vegetables (28.4%), beverages and alcohols (11.2%), and legumes and
legume products (5.5%), in particular, grapes, persimmons, mandarins, apples, and
green tea, were major food sources of dietary TAC. In addition, the consumption
of nutrient-dense foods, such as fruits and vegetables, increased, whereas the
intake of energy and fat decreased across quartiles of energy-adjusted dietary
TAC. CONCLUSIONS: The present study documented the baseline dietary TAC of Korean
adults and the major food sources thereof using nationally representative data.
Further research on the health effects of dietary TAC among Korean adults is
warranted.
PMID- 28405812
TI - Estimating the prevalence of functional exonic splice regulatory information.
AB - In addition to coding information, human exons contain sequences necessary for
correct splicing. These elements are known to be under purifying selection and
their disruption can cause disease. However, the density of functional exonic
splicing information remains profoundly uncertain. Several groups have
experimentally investigated how mutations at different exonic positions affect
splicing. They have found splice information to be distributed widely in exons,
with one estimate putting the proportion of splicing-relevant nucleotides at
>90%. These results suggest that splicing could place a major pressure on exon
evolution. However, analyses of sequence conservation have concluded that the
need to preserve splice regulatory signals only slightly constrains exon
evolution, with a resulting decrease in the average human rate of synonymous
evolution of only 1-4%. Why do these two lines of research come to such different
conclusions? Among other reasons, we suggest that the methods are measuring
different things: one assays the density of sites that affect splicing, the other
the density of sites whose effects on splicing are visible to selection. In
addition, the experimental methods typically consider short exons, thereby
enriching for nucleotides close to the splice junction, such sites being enriched
for splice-control elements. By contrast, in part owing to correction for
nucleotide composition biases and to the assumption that constraint only operates
on exon ends, the conservation-based methods can be overly conservative.
PMID- 28405815
TI - Reply to Letter to the Editor to "Soy isoflavone intake and prevalence of
depressive symptoms during pregnancy in Japan: baseline data from the Kyushu
Okinawa Maternal and Child Health Study".
PMID- 28405814
TI - Effects of coconut oil consumption on energy metabolism, cardiometabolic risk
markers, and appetitive responses in women with excess body fat.
AB - PURPOSE: Virgin coconut oil (VCO) is a medium-chain fatty acid source with
popularly attributed benefits on obesity management. However, its role on obesity
requires elucidation due to its saturated nature. In the study herein, we
investigated acute effects of VCO consumption on energy metabolism,
cardiometabolic risk markers, and appetitive responses in women with excess body
fat. METHODS: Fifteen adult women with excess body fat (37.43 +/- 0.83%)
participated in this randomized, crossover, controlled study. Two isocaloric
mixed breakfasts containing 25 mL of VCO or control (extra-virgin olive oil-C)
were evaluated. Resting energy expenditure (REE), fat oxidation rate (FOR), diet
induced thermogenesis (DIT) and appetitive subjective responses were assessed at
fasting and postprandial periods (up to 240 min). Cardiometabolic risk markers
were assessed at fasting and up to 180 min postprandially. RESULTS: VCO did not
affect REE, FOR, and DIT compared to C. In addition, VCO did not cause
deleterious change in triglycerides, total cholesterol, HDL-c, LDL-c,
triglycerides/HDL-c ratio, uric acid, glucose and Homeostasis Model Assessment of
Insulin Resistance Index (HOMA-IR) (P time*treatment > 0.05). However, VCO
suppressed less hunger (P time*treatment = 0.003), total satiety (P iAUC = 0.021)
and total fullness (P iAUC = 0.035) responses than C. CONCLUSIONS: VCO
consumption did not acutely change energy metabolism and cardiometabolic risk
markers when added to a mixed breakfast but promoted less appetitive responses.
PMID- 28405816
TI - Comments on "Soy isoflavone intake and its association with depressive symptoms
during pregnancy": consider sleep and physical activity as possible confounders.
PMID- 28405817
TI - Comment to: Soy isoflavone intake and prevalence of depressive symptoms during
pregnancy in Japan: baseline data from the Kyushu Okinawa Maternal and Child
Health Study.
PMID- 28405818
TI - Soy isoflavone intake and depressive symptoms during pregnancy.
PMID- 28405819
TI - Reply to letter to the editor to "Soy isoflavone intake and prevalence of
depressive symptoms during pregnancy in Japan: baseline data from the Kyushu
Okinawa Maternal and Child Health Study".
PMID- 28405821
TI - [Stem cell-based approaches to diseases of the ocular surface].
PMID- 28405820
TI - Higher dietary acid load is associated with a higher prevalence of frailty,
particularly slowness/weakness and low physical activity, in elderly Japanese
women.
AB - OBJECTIVE: Epidemiologic evidence on the potential effects of dietary acid load
on frailty is lacking. This cross-sectional study examined the association
between dietary acid load and frailty. METHODS: This study was based on self
reported data obtained from 2176 Japanese women aged 65-94 years. Dietary acid
load was characterized as potential renal acid load (PRAL) and net endogenous
acid production (NEAP), based on information on nutrient intake, obtained from a
validated brief diet history questionnaire. Frailty score (0-5) was defined as
the sum of slowness/weakness (two points), exhaustion (one point), low physical
activity (one point), and unintentional weight loss (one point). A score of >=3
was classified as indicating frailty. RESULTS: The prevalence of frailty was
17.9%. After adjustment for potential confounding factors, higher PRAL and NEAP
were associated with a higher prevalence of frailty. Adjusted OR (95% CI) for
frailty in the highest compared to the lowest quintiles was 1.59 (1.08, 2.34) for
PRAL (P for trend = 0.048) and 1.42 (0.98, 2.06) for NEAP (P for trend = 0.03).
PRAL and NEAP also showed positive associations with the prevalence of
slowness/weakness and low physical activity (all P for trend <=0.03). PRAL (but
not NEAP) was positively associated with the prevalence of exhaustion (P for
trend = 0.04). There was no association for unintentional weight loss.
CONCLUSIONS: Dietary acid load was positively associated with the prevalence of
frailty, particularly slowness/weakness and low physical activity, in elderly
Japanese women.
PMID- 28405824
TI - Redo renal denervation using a multi-electrode radiofrequency system in patients
with persistent therapy-resistant hypertension.
AB - OBJECTIVES: Renal sympathetic denervation has been studied as a potential
therapeutic option for patients with therapy-resistant hypertension; however, a
significant proportion of patients do not show a significant reduction in blood
pressure and are classified as non-responders. The objective of the present study
was to assess whether a redo renal denervation procedure increases response
rates. METHODS: We present a case series of three consecutive renal denervation
non-responders treated with the multi-electrode radiofrequency St. Jude EnligHTN
catheter after an average of 22 months. Patients were followed for 6 months.
RESULTS: Mean age was 66 years and two patients were male. Patients were
previously treated using either ReCor's Paradise system, the Vessix V2 system or
the Covidien OneShot system. Mean office blood pressure one year after the
initial procedure was 187/102 mm Hg with a mean 24 h ambulatory blood pressure of
166/102 mm Hg. All patients underwent a successful redo procedure using the
EnligHTN system because of persistent therapy-resistant hypertension. At 6 months
a significant drop in both office and ambulatory blood pressure of -27/-6 mm Hg
and -15/-13 mm Hg, respectively, was observed. No significant renal artery
stenosis was observed at 6 months. CONCLUSIONS: In patients with therapy
resistant hypertension who do not respond to an initial renal denervation
procedure, a redo procedure using the St. Jude EnligHTN system may help to
significantly improve blood pressure control.
PMID- 28405825
TI - Use of bisphosphonate might be important to improve bone mineral density in
patients with rheumatoid arthritis even under tight control: the TOMORROW study.
AB - Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight
control of disease activity might have a positive effect on bone metabolism. We
aimed to determine whether bisphosphonate use is still important to improve bone
mineral density (BMD) in RA patients whose disease activity was tightly
controlled and the dose of glucocorticoid was reduced. This study was a sub
analysis of the 10-year prospective cohort TOtal Management Of Risk factors in
Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW
which started from 2010. We compared BMD between 192 patients with RA and age-
and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray
absorptiometry (DXA) in whole body mode. We then determined ratios of changes in
BMD (%DeltaBMD) to assess factors influencing increases in BMD among the patients
using multivariate logistic regression analysis. The BMD was significantly lower
in the patients than in the controls at all sites surveyed during 2010 and 2013.
The %DeltaBMD of the total spine was significantly higher among the patients
treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001).
Multivariate logistic regression analysis revealed that use of bisphosphonate was
a significant factor contributing to BMD increase (odds ratio 2.13; 95%
confidence interval, 1.03-4.38, P = 0.041). Meanwhile, use of biologic agents,
reducing glucocorticoid dose, and control of disease activity were not
significant factors for gain of BMD. The BMD was lower among patients with RA
than non-RA controls. Use of bisphosphonate significantly increased the BMD of
the spine in patients over a period of 3 years and was important for maintaining
the BMD among patients with RA under the control of inflammation and disease
activity.
PMID- 28405826
TI - Everolimus as first line therapy for pancreatic neuroendocrine tumours: current
knowledge and future perspectives.
AB - PURPOSE: Everolimus has been shown to be effective for advanced pancreatic
neuroendocrine tumours (pNETs), but its positioning in the therapeutic algorithm
for pNETs is matter of debate. METHODS: With the aim to shed light on this point,
we performed an up-to-date critical review taking into account the results of
both retrospective and prospective published studies, and the recommendations of
international guidelines. In addition, we performed an extensive search on the
Clinical Trial Registries databases worldwide, to gather information on the
ongoing clinical trials related to this specific topic. RESULTS: We identified
eight retrospective published studies, two prospective published studies, and
five registered clinical trials. Moreover, we analyzed the content of four
widespread international guidelines. CONCLUSIONS: Our critical review confirms
the lack of high-quality data to recommend everolimus as the first line therapy
for pNETs. The ongoing clinical trials reported in this review will hopefully
help clinicians, in the near future, to better evaluate the role of everolimus as
the first line therapy for pNETs. However, at the moment, there is already enough
evidence to recommend everolimus as the first line therapy for patients with
symptomatic malignant unresectable insulin-secreting pNETs, to control the
endocrine syndrome regardless of tumour growth.
PMID- 28405828
TI - Copy number variants of ABCF1, IL17REL, and FCGR3A are associated with the risk
of gout.
PMID- 28405827
TI - MGMT promoter methylation status in Merkel cell carcinoma: in vitro versus
invivo.
AB - PURPOSE: Expression of O6-methylguanine-DNA methyltransferase (MGMT) in Merkel
cell carcinoma (MCC) is very variable; thus, we tested whether this may be due to
differential methylation of the MGMT gene promoter. METHODS: Quantitative
analysis of MGMT mRNA and protein expression, as well as MGMT promoter
methylation status, was performed in a series of tissue samples of MCC tumors,
representing both primary and metastatic lesions, as well as in six MCC cell
lines. RESULTS: These analyses revealed a very heterogeneous MGMT mRNA and
protein expression in MCC both in vivo and in vitro. However, neither the MGMT
mRNA nor protein expression correlated with the sensitivity of MCC cell lines
toward the alkylating agent dacarbazine in vitro. Notably, increased methylation
at the promoter of the MGMT gene was observed in 2/6 (33%) of the MCC cell lines;
however, MGMT promoter methylation was absent in all MCC tissue samples.
According to our results, albeit aberrant methylation of MGMT gene promoter can
be observed in in vitro propagated MCC cell lines, it seems to be absent or very
rare in MCC lesions in situ. CONCLUSION: Thus, the evaluation of this marker has
no or only little significance for predicting response to therapy or for
improving efficacy of demethylating agents in the treatment of MCC.
Microenvironmental factors may play a role in explaining the different results
between MCC cell lines and MCC samples.
PMID- 28405829
TI - An optical material for the detection of trace S2O32- in milk based on a copper
complex.
AB - A novel S2O32- luminescent sensor (Cu2+-p-CPIP) was developed and the presence of
S2O32- caused an obvious fluorescence enhancement at 420 nm upon excitation at
330 nm, which could be distinguished with the naked eye under a UV lamp.
Remarkably, the compound exhibited excellent selective and sensitive response to
S2O32- over other common anions with a micromolar limit of detection (0.442 MUM)
in DMSO/H2O (v/v, 1:1) buffer. The absorbance intensity and the color of Cu2+-p
CPIP solution changed gradually with the increase of S2O32- concentration. The
proposed method was applied to the determination of S2O32- in milk samples and
the recoveries were 97.5-105%. The preparation of Cu2+-p -CPIP exhibited the
quick, simple and facile advantages. The results showed that Cu2+-p -CPIP can be
a good candidate for simple, rapid and sensitive colorimetric detection of S2O32-
in aqueous solution.
PMID- 28405830
TI - Low yield of ventilation and perfusion imaging for the evaluation of pulmonary
embolism after indeterminate CT pulmonary angiography.
AB - PURPOSE: Ventilation and perfusion (VQ) imaging is common following suboptimal CT
pulmonary angiogram (CTPA) for pulmonary embolism (PE) evaluation; however, the
results of this diagnostic pathway are unclear. The purpose of our study is to
determine the incidence of PE diagnosed on VQ scans performed in patients with
suboptimal CTPAs. METHODS: One hundred twenty-two suboptimal CTPAs with
subsequent VQ scans within 1 week were retrospectively identified. VQ reports
utilizing modified prospective investigation of pulmonary embolism diagnosis
(PIOPED) and prospective investigative study of acute pulmonary embolism
diagnosis (PISAPED) criteria were evaluated for presence of PE; intermediate
probability, high probability, and PE present were considered PE positive. Three
hundred consecutive reports of each diagnostic CTPA and diagnostic VQ studies
were reviewed to estimate baseline PE positive rates at our institution. These
were compared to the positive VQ scan rate after suboptimal CTPA by Fisher's
exact test. Reported reason for suboptimal CTPA was noted. When contrast bolus
timing was suboptimal, we measured main pulmonary artery (mPA) Hounsfield units
(HU). Potential alternative diagnoses in CTPA reports were noted. RESULTS: 97.5%
(119/122) of VQ scans following suboptimal CTPA were negative for PE, and 2.5%
(3/122) were positive for PE. This was significantly lower than baseline PE
positive rate of 10.7% (32/300, p < 0.01) for VQ imaging, and 10.3% (31/300, p <
0.01) for CTPA at our institution. Most (79.5%) CTPAs were suboptimal due to
contrast timing. Average mPA density in these cases was 164 +/- 61 HU. Most of
these studies ruled out central PE. Potential alternative diagnosis was reported
in 34/122 (28%) of suboptimal CTPAs, for which pneumonia accounted 59%.
CONCLUSION: There is very low incidence of PE diagnosed on VQ imaging performed
after suboptimal CTPA. This may be attributed to the ability of most suboptimal
CTPAs to rule out central PE.
PMID- 28405832
TI - Editorial: special issue introduction.
PMID- 28405831
TI - Demographic Characteristics, Components of Sexuality and Gender, and Minority
Stress and Their Associations to Excessive Alcohol, Cannabis, and Illicit
(Noncannabis) Drug Use Among a Large Sample of Transgender People in the United
States.
AB - The current study examined demographics, sexual orientation, gender
characteristics, and gender minority stress and their association to excessive
alcohol, cannabis, and illicit (noncannabis) drug use among 1210 transgender
adults living in the United States. The authors conducted a secondary analysis of
data that included 680 transgender women (M age = 32.63, SD age = 12.29) and 530
transgender men (M age = 26.14, SD age = 7.42). A modified version of the Risk
Behavioral Assessment quantified participants' alcohol, cannabis, and illicit
drug use in the past 3 months. Overall, 21.5% of participants reported excessive
alcohol use; no significant differences were found on the rates of excessive
alcohol use between transgender women and men. Cannabis use among our sample was
24.4%; trangender men reported significantly higher rates of cannabis use
compared to transgender women. Illicit drug (noncannabis) use among our sample
was 11.6%; transgender men also reported significantly higher rates of illicit
drug use compared to transgender women. Multivariate analyses suggested that
gender dysphoria was significantly associated with: excessive alcohol use for
transgender women, cannabis use among both transgender women and men, and illicit
(noncannabis) drug use among transgender women. A nonheterosexual orientation was
associated with increased odds of cannabis use among transgender women and men; a
nonheterosexual orientation was associated with greater odds of illicit substance
use among transgender men but not among transgender women. Gender minority
stressors were independently associated with excessive alcohol use among
transgender men and cannabis use among transgender women. The authors suggest
that minority stress may only partially account for substance use among
transgender people. Consequently, the authors suggest that in addition to
minority stress, other biopsychosocial mechanisms should continue to be examined
to identify pathways that may lead to the development of effective substance use
prevention efforts and treatment programs.
PMID- 28405833
TI - Interpathologist concordance in the histological diagnosis of focal prostatic
atrophy lesions, acute and chronic prostatitis, PIN, and prostate cancer.
AB - Epidemiological and biological evidence indicates a causal relationship between
the presence of proliferative atrophic lesions and the development of prostatic
intraepithelial neoplasia (PIN) and prostate cancer. The presence of inflammatory
and atrophic lesions of the prostate is widely underestimated and they are not
generally mentioned in pathology reports. We performed a histopathological
concordance study among eight genitourinary specialists and seven generalist
pathologists, using 116 histological slides of prostate lesions, including
proliferative atrophic lesions, PIN, and cancer. The overall agreement between
all possible pairs of reviewers was 80% for prostate cancer, 67% for PIN, and 49%
for proliferative atrophic lesions. When using as gold standard the assessment of
a single genitourinary pathologist, the mean agreement percentage increased to
97% for prostate cancer, 92% for PIN, and 72% for proliferative atrophic lesions.
PMID- 28405834
TI - Feasibility Study of a Generalized Framework for Developing Computer-Aided
Detection Systems-a New Paradigm.
AB - We propose a generalized framework for developing computer-aided detection (CADe)
systems whose characteristics depend only on those of the training dataset. The
purpose of this study is to show the feasibility of the framework. Two different
CADe systems were experimentally developed by a prototype of the framework, but
with different training datasets. The CADe systems include four components;
preprocessing, candidate area extraction, candidate detection, and candidate
classification. Four pretrained algorithms with dedicated optimization/setting
methods corresponding to the respective components were prepared in advance. The
pretrained algorithms were sequentially trained in the order of processing of the
components. In this study, two different datasets, brain MRA with cerebral
aneurysms and chest CT with lung nodules, were collected to develop two different
types of CADe systems in the framework. The performances of the developed CADe
systems were evaluated by threefold cross-validation. The CADe systems for
detecting cerebral aneurysms in brain MRAs and for detecting lung nodules in
chest CTs were successfully developed using the respective datasets. The
framework was shown to be feasible by the successful development of the two
different types of CADe systems. The feasibility of this framework shows promise
for a new paradigm in the development of CADe systems: development of CADe
systems without any lesion specific algorithm designing.
PMID- 28405835
TI - High-yield production of pure tagatose from fructose by a three-step enzymatic
cascade reaction.
AB - OBJECTIVE: To produce tagatose from fructose with a high conversion rate and to
establish a high-yield purification method of tagatose from the reaction mixture.
RESULTS: Fructose at 1 M (180 g l-1) was converted to 0.8 M (144 g l-1) tagatose
by a three-step enzymatic cascade reaction, involving hexokinase, plus ATP,
fructose-1,6-biphosphate aldolase, phytase, over 16 h with a productivity of 9 g
l-1 h-1. No byproducts were detected. Tagatose was recrystallized from ethanol to
a purity of 99.9% and a yield of 96.3%. Overall, tagatose at 99.9% purity was
obtained from fructose with a yield of 77%. CONCLUSION: This is the first
biotechnological production of tagatose from fructose and the first application
of solvent recrystallization for the purification of rare sugars.
PMID- 28405836
TI - Chondrogenesis and hypertrophy in response to aggregate behaviors of human
mesenchymal stem cells on a dendrimer-immobilized surface.
AB - OBJECTIVES: To investigate the behaviors of aggregates of human mesenchymal stem
cells (hMSCs) on chondrogenesis and chondrocyte hypertrophy using spatiotemporal
expression patterns of chondrogenic (type II collagen) and hypertrophic (type X
collagen) markers during chondrogenesis. RESULTS: hMSCs were cultured on either a
polystyrene surface or polyamidoamine dendrimer surface with a fifth generation
(G5) dendron structure in chondrogenic medium and growth medium. At day 7, cell
aggregates without stress fibers formed on the G5 surface and triggered
differentiation of hMSCs toward the chondrogenic fate, as indicated by type II
collagen being observed while type X collagen was undetectable. In contrast,
immunostaining of hMSCs cultured on polystyrene, which exhibited abundant stress
fibers and did not form aggregates, revealed no evidence of either type II and or
type X collagen. At day 21, the morphological changes of the cell aggregates
formed on the G5 surface were suppressed as a result of stress fiber formation.
Type II collagen was observed throughout the aggregates whereas type X collagen
was detected only at the basal side of the aggregates. Change of cell aggregate
behaviors derived from G5 surface alone regulated chondrogenesis and hypotrophy,
and this was enhanced by chondrogenic medium. CONCLUSIONS: Incubation of hMSCs
affects the expression of type II and X collagens via effects on cell aggregate
behavior and stress fiber formation.
PMID- 28405837
TI - The nuclear 28S gene fragment D3 as species marker in oribatid mites (Acari,
Oribatida) from German peatlands.
AB - To make oribatid mites an applicable tool in monitoring programs it is necessary
to find a molecular species marker that allows distinct, rapid and easy species
identification. In previous studies, the common barcoding sequence COI showed to
be too variable to serve as species marker in oribatid mites. The aim of the
present study is to evaluate the potential use of the D3 region of the nuclear
28S rDNA gene for species identification. Therefore, we generated a reference DNA
library of 28S D3 to identify specimens of the Oribatida from Germany, with focus
on species occurring in peatlands being one of the most endangered habitats in
Europe. New DNA sequences were obtained from 325 individuals and 64 species (58
genera, 34 families). By adding 28S D3-sequences from GenBank we altogether
analysed 385 sequences from 89 German species, 32 of them restricted to peatlands
and further 42 occurring in peatlands occasionally, representing 46 and 33% of
the oribatids in German peatlands, respectively. P-distances were measured
between species within families as well as for intraspecific divergence. 28S D3
showed low intraspecific genetic p-distances between 0 and 0.5%, interspecific
distances within families varied between 0 and 9.7%. Most species pairs within
families were further separated by one to four indels in addition to
substitutions. Altogether, 93% of all analysed species are clearly delineated by
28S D3. Our study emphasises that 28S D3 rDNA is a useful barcode for the
identification of oribatid mite specimens and represents an important step in
building-up a comprehensive barcode library to allow metabarcoding analyses of
environmental peatland samples for Oribatida in Germany as well as in Central
Europe.
PMID- 28405838
TI - Acaricidal and sublethal effects of a Chenopodium-based biopesticide on the two
spotted spider mite (Acari: Tetranychidae).
AB - Acaricidal and sublethal effects of the biopesticide Requiem(r)EC (containing an
essential oil extract of Chenopodium ambrosioides near ambrosioides) on the two
spotted spider mite, Tetranychus urticae Koch, were evaluated in laboratory
bioassays. The biopesticide was applied to bean leaves or leaf discs using a
Potter spray tower. Acaricidal activity against eggs and immatures was evaluated
in successive acute toxicity bioassays. Concentration-mortality data were
subjected to probit analysis and the following LC50 values (ml/l) were
calculated: 2.47 (eggs), 0.71 (larvae), 1.13 (protonymphs), 2.23 (female
deutonymphs), and 6.02 (female teleiochrysalises). In adult bioassay, in which
pre-ovipositional females were treated with a series of concentrations (0.31-10
ml/l), a run-off effect ranging 4-80% (after 24 h) and 8-93% (after 72 h) was
observed. In two-choice bioassay, T. urticae females preferred the untreated
halves of leaves over the halves treated with 1.25-10 ml/l biopesticide and they
laid significantly more eggs on the untreated halves in the first 24 h and summed
over 72 h. The indices of repellency and oviposition deterence ranged 11.2-77.3
and 14.8-87.9%, respectively. In age-stage two-sex life table bioassay, the
females that hatched from eggs treated with 2.5 ml/l biopesticide and reached
adulthood on treated leaf surface showed a significantly reduced the intrinsic
rate of increase (r = 0.222), compared to the control (r = 0.317). The reduction
of population growth was mainly due to a reduced preadult survival rate (0.42 +/-
0.04) and extended juvenile developmental time (9.27 +/- 0.11 days), compared to
the control (0.93 +/- 0.03 and 7.70 +/- 0.06 days, respectively).
PMID- 28405839
TI - Molecular and morphological identification of a human biting tick, Amblyomma
testudinarium (Acari: Ixodidae), in Taiwan.
AB - Genetic identity and morphological features of a human biting tick, Amblyomma
testudinarium, were determined for the first time in Taiwan. Morphological
features of adult male and female ticks of Am. testudinarium were observed and
photographed by a stereo- microscope. The genetic identity was analyzed by
comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 18
strains of ticks representing 10 species of Amblyomma, and four outgroup species
of Dermacentor and Rhipicephalus ticks. Nine major clades could be easily
distinguished by neighbour-joining analysis and were congruent by maximum
parsimony method. All these Am. testudinarium ticks collected from Taiwan and
Japan were genetically affiliated to a monophyletic group with highly homogeneous
sequence (99.8-100% similarity), and can be discriminated from other species of
Amblyomma and other genera of ticks (Dermacentor and Rhipicephalus) with a
sequence divergence ranging from 6.9 to 23.9%. Moreover, intra- and inter-species
analysis based on the genetic distance (GD) values indicated a lower level (GD <
0.003) within the same lineage of Am. testudinarium ticks collected from Taiwan
and Japan, as compared with other lineage groups (GD > 0.108) of Amblyomma ticks,
as well as outgroup (GD > 0.172) species. Our results provide the first
distinguished features of adult Am. testudinarium ticks and the first genetic
identification of Am. testudinarium ticks collected from humans in Taiwan.
Seasonal prevalence, host range, and vectorial capacity of this tick species in
Taiwan need to be further clarified.
PMID- 28405840
TI - Increased activities of peroxidase and polyphenol oxidase enhance cassava
resistance to Tetranychus urticae.
AB - In order to study the function of peroxidase (POD) and polyphenol oxidase (PPO)
in cassava resistance to spider mites, we tested the changes of transcription
levels and activities of these two protective enzymes in both cassava and
Tetranychus urticae (=T. cinnabarinus) during the interaction. The results showed
that after damage of the mite-susceptible cassava cultivar BRA900 by T. urticae
for 1 and 8 days, the transcription levels of MePOD and MePPO and the activities
of POD and PPO showed no significant difference compared with those in undamaged
leaves. However, the corresponding transcription levels and activities in 1- and
8-day-damaged leaves of mite-resistant cassava cultivar C1115 increased to a
significant level of approximately twofold. When T. urticae fed on BRA900 for 1
and 8 days, the transcription levels of TcPPO and TcPOD and the activities of PPO
and POD showed no significant difference compared with those before feeding.
However, the corresponding transcription levels and activities of these two
protective enzymes in T. urticae feeding on C1115 significantly decreased by
about half. This study preliminarily validates the function of POD and PPO in
cassava resistance to T. urticae, and provides candidate gene resource for
molecular breeding of spider mite-resistant cassava.
PMID- 28405841
TI - Focal segmental glomerulosclerosis and medullary nephrocalcinosis in children
with ADCK4 mutations.
AB - BACKGROUND: Mutations in the AarF domain containing kinase 4 gene (ADCK4), one of
the novel genes causing steroid-resistant nephrotic syndrome (SRNS), usually
manifest as isolated adolescent-onset focal segmental glomerulosclerosis (FSGS).
ADCK4 interacts with components of the coenzyme Q10 (CoQ10) biosynthesis pathway.
METHODS: The incidence and phenotypes of patients with ADCK4 mutations were
investigated in a cohort of Korean pediatric patients with SRNS. RESULTS: Among
the 53 patients enrolled in the study the incidence of ADCK4-associated FSGS was
7.5% (n = 4) in children aged 5 years and older with multidrug-resistant FSGS.
Two additional patients were included for phenotype analyses, one detected by
family screening and the other with cyclosporine-responsive FSGS. These six
patients presented proteinuria without overt nephrotic syndrome at a median age
of 110 (range 60-153) months, of whom five progressed to end-stage renal disease
within a median period of 46 (range 36-79) months after onset. Renal biopsies
revealed mitochondrial abnormalities in podocytes and tubular cells of all
patients. Notably, all patients showed accompanying medullary nephrocalcinosis.
None of the patients showed other extrarenal manifestations. CONCLUSIONS: ADCK4
mutations should be considered in older children presenting with steroid
resistant FSGS. An early diagnosis of ADCK4 mutations is essential because the
condition is treatable with CoQ10 supplementation at an early stage. The
association with medullary nephrocalcinosis may be an additional diagnostic
indicator.
PMID- 28405842
TI - EGFR-targeting peptide-coupled platinum(IV) complexes.
AB - The high mortality rate of lung cancer patients and the frequent occurrence of
side effects during cancer therapy demonstrate the need for more selective and
targeted drugs. An important and well-established target for lung cancer
treatment is the occasionally mutated epidermal growth factor receptor (EGFR). As
platinum(II) drugs are still the most important therapeutics against lung cancer,
we synthesized in this study the first platinum(IV) complexes coupled to the EGFR
targeting peptide LARLLT (and the shuffled RTALLL as reference). Notably, HPLC-MS
measurements revealed two different peaks with the same molecular mass, which
turned out to be a transcyclization reaction in the linker between maleimide and
the coupled cysteine moiety. With regard to the EGFR specificity, subsequent
biological investigations (3-day viability, 14-day clonogenic assays and platinum
uptake) on four different cell lines with different verified EGFR expression
levels were performed. Unexpectedly, the results showed neither an enhanced
activity nor an EGFR expression-dependent uptake of our new compounds.
Consequently, fluorophore-coupled peptides were synthesized to re-evaluate the
targeting ability of LARLLT itself. However, also with these molecules, flow
cytometry measurements showed no correlation of drug uptake with the EGFR
expression levels. Taken together, we successfully synthesized the first
platinum(IV) complexes coupled to an EGFR-targeting peptide; however, the
biological investigations revealed that LARLLT is not an appropriate peptide for
enhancing the specific uptake of small-molecule drugs into EGFR-overexpressing
cancer cells.
PMID- 28405843
TI - Quality of life of patients treated for giant cell arteritis: a case-control
study.
AB - The objective of the study was to assess the quality of life (QOL) of patients
with giant cell arteritis (GCA), following high dose of corticosteroids (CS).
Thirty patients with GCA who had stopped CS or who were under long-term low dose
of CS were included and matched to 60 controls. QOL was measured by the SF-36
score and a specific questionnaire. GCA patients had no impairment of QOL
compared to controls according to SF-36. Most of them (57%) estimated that their
general condition was improved following treatment. Patients with GCA
complications or CS therapy side effects had no significant impairment of their
QOL compared with patients without complications or adverse effects. Only the
patients who had gained weight had a lower score on the domain "Vitality" (VT; p
= 0.013). Walking difficulties were the most frequent complaints. They were
associated with impaired scores on the physical summary score (p = 0.0340) and on
the "General Health" (GH; p = 0.005) and "Physical Functioning" (PF, p = 0.0298)
domains. Falls among GCA patients were associated with altered scores on the
domain VT (p = 0.0058) and on the mental summary score if they had fallen at
least three times (p = 0.0460). GCA patients following high dose of CS or under
long-term low doses of CS have no significant impairment of their QOL compared to
controls. GCA complications, including visual impairment, do not seem to have any
major impact on QOL.
PMID- 28405844
TI - Presidents' Day reflections. Why Donald Trump could not be a rheumatologist.
PMID- 28405845
TI - Anxiety after completion of treatment for early-stage breast cancer: a systematic
review to identify candidate predictors and evaluate multivariable model
development.
AB - PURPOSE: The purpose of this review was to identify potential candidate
predictors of anxiety in women with early-stage breast cancer (BC) after adjuvant
treatments and evaluate methodological development of existing multivariable
models to inform the future development of a predictive risk stratification model
(PRSM). METHODS: Databases (MEDLINE, Web of Science, CINAHL, CENTRAL and
PsycINFO) were searched from inception to November 2015. Eligible studies were
prospective, recruited women with stage 0-3 BC, used a validated anxiety outcome
>=3 months post-treatment completion and used multivariable prediction models.
Internationally accepted quality standards were used to assess predictive risk of
bias and strength of evidence. RESULTS: Seven studies were identified: five were
observational cohorts and two secondary analyses of RCTs. Variability of
measurement and selective reporting precluded meta-analysis. Twenty-one candidate
predictors were identified in total. Younger age and previous mental health
problems were identified as risk factors in >=3 studies. Clinical variables (e.g.
treatment, tumour grade) were not identified as predictors in any studies. No
studies adhered to all quality standards. CONCLUSIONS: Pre-existing vulnerability
to mental health problems and younger age increased the risk of anxiety after
completion of treatment for BC survivors, but there was no evidence that
chemotherapy was a predictor. Multiple predictors were identified but many lacked
reproducibility or were not measured across studies, and inadequate reporting did
not allow full evaluation of the multivariable models. The use of quality
standards in the development of PRSM within supportive cancer care would improve
model quality and performance, thereby allowing professionals to better target
support for patients.
PMID- 28405847
TI - Link between generalized nonidempotency and complexity measures.
AB - The nonidempotency measure of Lowdin is found to be proportional to the
disequilibrium. It is shown that there exists a simple relationship between the
LMC (Lopez-Ruiz-Mancini-Calbet) and the generalized statistical complexities and
the generalized nonidempotency measure of Lowdin. Results are illustrated for an
exactly solvable two-electron model atom.
PMID- 28405846
TI - Cancer-specific geriatric assessment and quality of life: important factors in
caring for older patients with aggressive B-cell lymphoma.
AB - PURPOSE: To evaluate the efficacy and tolerability of chemotherapy, a geriatric
assessment is recommended in elderly patients with cancer. We aimed to
characterize and compare patients with aggressive lymphoma by objective response
and survival status based on pre-treatment cancer-specific geriatric (C-SGA) and
quality of life (QoL) assessments. METHODS: Patients not eligible for
anthracycline-based first-line therapy or intensive salvage regimens completed C
SGA and QoL assessment before and after a rituximab-bendamustine-lenalidomide (R
BL) treatment in a phase II clinical trial. Clinical outcomes were compared based
on pre-treatment individual and summary C-SGA measures, their cutoff-based
subcategories and QoL indicators, using Wilcoxon rank sum or chi-square tests.
RESULTS: A total of 57 patients (41 included in the clinical trial) completed a C
SGA. Participants with pre-treatment impaired functional status (Vulnerable
Elders Survey-13 score >=3) were more likely to experience worse outcomes: a
higher proportion were non-responders, died before the median follow-up of 31.6
months (interquartile range (IQR) 27.9-37.9) or died during treatment. Non
responders were patients categorized as having possible depression (Geriatric
Depression Scale-5 score >=2) and with worse QoL scores for functional
performance. Patients with worse C-SGA summary scores and with greater tiredness
were more likely to die during treatment. CONCLUSION: A pre-treatment impaired
functional status is an important factor with respect to clinical outcomes in
patients receiving an R-BL regimen. Individual geriatric and related QoL domains
showed similar associations with clinical outcomes. Whether interventions
targeting specific geriatric dimensions also translate in better symptom- or
domain-specific QoL warrants further research.
PMID- 28405848
TI - Expert's comment concerning Grand Rounds case entitled "Intracardiac bone cement
embolism as a complication of vertebroplasty: management strategy" by Hatzantonis
C, Czyz M, Pyzik R, Boszczyk BM. (Eur Spine J; 2016. doi:10.1007/s00586-016-4695
x).
PMID- 28405849
TI - Hypomethylation agent decitabine restores drug sensitivity by depressing P
glycoprotein activity through MAPK signaling pathway.
AB - The multidrug resistance (MDR) continues to be an obstacle in the treatment of
both hematological and solid tumors. Hypomethylation agent, decitabine (5-Aza
dC), is an experimental agent in MDR therapy, while the mechanism is not very
clear. In the present study, we demonstrated 5-Aza-dC may reverse MDR induced by
P-glycoprotein (P-gp) coded by mdr1 gene in both hematologic K562/ADR cells and
solid tumor MCF-7/ADR cells with time and dose-dependent manner. 5-Aza-dC
significantly increased drug sensitivity in patients' leukemic cells which had
higher expression of mdr1 gene. Both total protein and membrane P-gp expression
were up-regulated with 5-Aza-dC treatment in K562/ADR and MCF-7/ADR cells.
However, accumulation of adriamycin and rhodamine 123 were increased which
suggested the depression of P-gp activity. Gene expression profiling was
performed and activation of MAPK signaling pathway was identified as the most
significant change affected by 5-Aza-dC. Inhibition of MAPK pathway could
increase P-gp activity. Our data suggested that hypomethylation agent decitabine
restores drug sensitivity in the P-gp-induced MDR phenotype by depressing of P-gp
activity as drug pump partly through MAPK signaling pathway.
PMID- 28405850
TI - Retrospective Study of Leptospirosis in Malaysia.
AB - Leptospirosis is a bacterial disease transmitted to humans and animals by direct
or indirect contact with urine or body fluids from infected animals especially
rodents. Infection can be associated with wide clinical spectrum varying from
asymptomatic to severe multi-organ syndrome with life-threatening consequences.
We conducted a review of published studies on incidences, case reports, sero
epidemiological surveys from year 2000 to 2015 using different electronic data
bases. Our study revealed that majority of the studies were conducted in
Peninsular Malaysia and predominantly among high-risk human groups. Most of the
studies on domestic animals were conducted in the 1980s; hence, the current
status of leptospirosis among domestic animal population remains largely unknown.
There tend to be a sharp rise in incidence rate among human population in the
year 2014 which was attributed to flooding and heavy rainfall experienced as well
as recreational activities. Several gaps in epidemiological knowledge were also
disclosed.
PMID- 28405851
TI - Fluoride Induces Neuroinflammation and Alters Wnt Signaling Pathway in BV2
Microglial Cells.
AB - Fluoride is a common element in nature and our daily life, and excessive intake
of this element can cause fluorosis and irreversible brain damage. The toxic
effects of fluoride on the central nervous system may be attributed to the
release of inflammatory cytokines and ROS. GSK3beta is a key protein that
modulates NF-kappaB activity and inflammatory cytokine levels and plays an
important role in the Wnt signaling pathway. In this study, we found that
fluoride altered the inflammatory status and oxidative stress by inhibiting Wnt
signaling pathway activity. This study thus provides a valid basis for the
fluorine-induced neuroinflammation injury theory.
PMID- 28405852
TI - Chlorinated Flavonoids Modulate the Inflammatory Process in Human Blood.
AB - Flavonoids are known to react with neutrophil-generated hypochlorous acid (HOCl)
at inflammation loci to form stable mono- and dichlorinated products. Some of
these products have been shown to retain or even enhance their inflammatory
potential, but further information is required in a broader approach to
inflammatory mechanisms. In that sense, we performed an integrated evaluation on
the anti-inflammatory potential of a panel of novel chlorinated flavonoids and
their parent compounds, in several steps of the complex inflammatory cascade,
namely, in the activity of cyclooxygenase (COX)-1 and COX-2, and in the
production of cytokines [interleukin (IL)-6, IL-1beta, tumor necrosis factor
(TNF)], and the chemokine, IL-8, as well as in the production of reactive
species, using human whole blood as a representative in vitro model,
establishing, whenever possible, a structure-activity relationship. Although
luteolin was the most active compound, chlorinated flavonoids demonstrated a
remarkable pattern of activity for the resolution of the inflammatory processes.
Our results demonstrated that 6-chloro-3',4',5,7-tetrahydroxyflavone deserves
scientific attention due to its ability to modulate the reactive species and
cytokines/chemokine production. In this regard, the therapeutic potential of
flavonoids' metabolites, and in this particular case the chlorinated flavonoids,
should not be neglected.
PMID- 28405853
TI - Age-Related Changes in Inflammatory Response after Experimental Envenomation:
Impact on the Susceptibility to Androctonus australis hector Venom.
AB - In regions at risk of scorpion envenomation, children remain the principal
victims; they exhibit severe symptoms and represent a higher mortality rate
compared to adults. The pathophysiology of envenomation is related to an
excessive inflammatory response; however, no studies have identified the
differences in immune responses to scorpion stings and mainly the mechanisms of
inflammation between children and adults, which may be a determinant key of the
susceptibility of children to scorpion envenomation. In this study, we compared
the systemic (blood and lung) and the central (brain) inflammatory responses
after injection of Androctonus australis hector (Aah) venom to 7 and 21 postnatal
days (pnds) and adult mice by subcutaneous route. Results revealed that 7 and 21
pnd mice were more sensitive to Aah venom than adults and presented also severe
systemic and central inflammatory responses characterized by a high activation of
immune cells, NO liberation, and lipid peroxidation. Lymphocyte levels were much
lower in young animals than in adults; however, neutrophil levels seemed to be
higher in immature mice. The antioxidant GSH and catalase levels were more
reduced in 7 and 21 pnd mice compared to adults leading to more pronounced
tissular alterations and edema formation in lung and brain. These findings show a
relationship between the severity of the pathophysiological effects of Aah venom
and the age. The vulnerability of immature animals to Aah venom might result from
uncontrolled inflammatory response and central nervous system alterations. Data
from the present study emphasize the need for the development of age-specific
therapeutic modalities.
PMID- 28405854
TI - Development of a new method for the preparation of an acellular allodermis,
quality control and cytotoxicity testing.
AB - Demand for use of acellular allodermis is high but commercially appropriate
products are not used routinely because of very high price and limited
availability. These facts did motivate us to prepare acellular allodermis using a
new, simple and less expensive method. We have developed a original method for
preparation of acellular allogeneic dermis based on action of a proteolytic
enzyme in combination with distilled water. Hypotonic environment in comparison
with SDS or Triton ansure no toxicity of the final product. Trials for
determination of optimal trypsin concentrations, temperature and time of action
were performed. According to our results, the use of 2.5% trypsin/EDTA solution
overnight at +4 degrees C was proving to be optimal. The histology confirmed
absence of cells in the prepared dermis. No toxicity of final acellular dermis
was confirmed by three independent tests (agar diffusion test contact
cytotoxicity test and grow curve). The prepared acellular dermis seems to be
suitable not only for direct clinical use, but it can be used as a scaffold for
cell cultivation as well.
PMID- 28405855
TI - Erratum to: What is the Diagnostic Accuracy of Aspirations Performed on Hips With
Antibiotic Cement Spacers?
PMID- 28405856
TI - What Injury Mechanism and Patterns of Ligament Status Are Associated With
Isolated Coronoid, Isolated Radial Head, and Combined Fractures?
AB - BACKGROUND: Isolated coronoid, isolated radial head, and combined coronoid and
radial head fractures are common elbow fractures, and specific ligamentous injury
of each fracture configuration has been reported. However, the osseous injury
mechanism related to ligament status remains unclear. QUESTIONS/PURPOSES: The
objectives of this study were: (1) to determine what ligamentous injury patterns
(medial or lateral collateral) and bone contusion patterns (medial or lateral)
are associated with isolated coronoid, isolated radial head, and combined
coronoid and radial head fractures; (2) to correlate the osseous injury mechanism
based on these findings with isolated coronoid, isolated radial head, and
combined coronoid and radial head fractures; and (3) to determine whether
isolated and combined coronoid fractures have different fracture lines through
the coronoid (tip or anteromedial facet), speculated to be caused by different
injury mechanisms. METHODS: Between June 2007 and June 2012, 100 patients with
elbow fractures were included in the cohort, with 46 of these patients being
excluded owing to incongruity for our surgical indication. Finally, 54 patients
with surgically treated elbow fractures who had MRI preoperatively were assessed
retrospectively. There were 17 elbows with isolated coronoid fractures, 22 with
isolated radial head fractures, and 15 with combined coronoid and radial head
fractures. Collateral ligament injury pattern and existence of distal humerus
bone contusion were reviewed on MR images. RESULTS: Patients with isolated radial
head fractures were at greater risk of medial collateral ligament rupture
compared with patients with isolated coronoid fractures (radial head only: 15 of
22 [68%]; coronoid only: three of 17 [18%]; odds ratio [OR], 10.0; 95% CI, 2.2
46.5; p = 0.002). Patients with isolated coronoid fractures had greater risk of
lateral ulnar collateral ligament ruptures (coronoid: 16 of 17 [94%]; radial
head: seven of 22 [32%]; OR, 3.5; 95% CI, 3.8-333.3; p < 0.001). The presence of
radial head fractures was associated with the risk of lateral bone bruising
(isolated radial head fracture: 32 of 37 [86%], isolated coronoid fracture: four
of 17 [24%]; OR, 29.6; 95% CI, 5.2-168.9; p < 0.001). Medial bone bruising was
only detected in isolated coronoid fractures (isolated coronoid fracture: 12 of
17 [71%], others: zero of 37 [0%]). All isolated coronoid fractures involved the
anteromedial facet of the coronoid (17 of 17; 100%). However, combined coronoid
and radial head fractures often involved the tip (13 of 15; 87%). CONCLUSIONS:
Isolated coronoid fractures mostly involved the anteromedial facet of the
coronoid process associated with lateral ulnar collateral ligament rupture and
medial bone bruising. However, isolated radial head fractures were associated
with medial collateral ligament rupture and lateral bone bruising. Combined
coronoid and radial head fractures mostly involved a tip fracture of the coronoid
with lateral ulnar collateral ligament rupture and lateral bone bruising. Thus
surgeons may predict which ligament they should be aware of in the surgical
field. LEVEL OF EVIDENCE: Level III, prognostic study.
PMID- 28405857
TI - Choosing a Career in Advanced Endoscopy or General Gastroenterology.
PMID- 28405858
TI - Word Naming in Bodo-Assamese Bilinguals: The Role of Semantic Context, Cognate
Status, Second Language Age of Acquisition and Proficiency.
AB - The current study investigated the effects of the semantic context, cognate
status of the word and second language age of acquisition and proficiency in two
word naming experiments (Experiment 1 and 2). Three groups of Bodo-Assamese
bilinguals named cognate and non-cognate words in their first language, Bodo and
second language, Assamese, which were presented in categorized and randomized
lists. Experiment 1 demonstrated significant category interference for both
cognate and non-cognate words; whereas, in Experiment 2, category interference
was observed only in case of cognate words, indicating that naming in L2 was more
prone to semantic effects. In Experiment 1, the magnitude of the category
interference effect was larger for the low proficient bilinguals, but in
Experiment 2, only the high proficient bilinguals demonstrated category
interference effect. Further, cognate facilitation effect was not observed in
both experiments which is in line with the findings of previous studies. The
findings are discussed in light of the predictions of the Revised Hierarchical
Model.
PMID- 28405859
TI - Effects of Mild Hypothermia on Cerebral Large and Small Microvessels Blood Flow
in a Porcine Model of Cardiac Arrest.
AB - BACKGROUND: The effect of mild hypothermia (MH) on microcirculation after
resuscitation from cardiac arrest is controversial. The aim of this study was to
determine whether MH improves or aggravates the disturbance of cerebral
microcirculation. METHODS: Twenty domestic male pigs were randomized into the MH
group (n = 8), non-hypothermia (NH) group (n = 8) or sham operation group (n =
4). In the MH group, the animals were initiated rapid intravascular cooling at 1
h after return of spontaneous circulation (ROSC) from 8 min ventricular
fibrillation, and the core temperature was reduced to 33 degrees C for 12 h and
then rewarmed to 37 degrees C. In the NH group, animals did not receive
hypothermia treatment after ROSC. In the sham operation group, the same surgical
procedure was performed, but without inducing ventricular fibrillation and
hypothermia treatment. The cerebral microvascular flow index (MFI) of large
microvessel (diameter > 20 MUm) and small microvessel (diameter < 20 MUm) was
measured after ROSC. Cerebral oxygen extraction ratio, internal jugular venous
artery lactate difference, and CO2 difference were also calculated. RESULTS:
Cerebral MFI dramatically reduced after ROSC, and MH further aggravated the
decrease in MFI of small microvessel compared with NH (p < 0.05). Internal
jugular venous-arterial lactate difference and CO2 difference, and oxygen
extraction ratio were all significantly increased after ROSC. MH significantly
decreased the values compared with NH (p < 0.05). CONCLUSIONS: MH decreases
cerebral small microvessel blood flow and cerebral metabolism after ROSC compared
with NH. However, the total effect is that cerebral oxygen supply-demand
relationship is improved during hypothermia.
PMID- 28405860
TI - Andre Tridon Jagendorf (1926-2017): a personal tribute.
AB - We present here our tribute to an outstanding unique scientist, a pioneer of
plant biochemistry, best known for his seminal ground-breaking discoveries
related to electron and proton transport, and their intimate relation to ATP
synthesis in chloroplasts. His dedication and in-depth understanding of science
was matched by his humor. Here, we offer a modest precis of his life and
research. We have also included Reminiscences from: Leonard Fish, Eric Larson,
Donald Ort, Thomas Owens, and Robert Turgeon.
PMID- 28405861
TI - pK a of ubiquinone, menaquinone, phylloquinone, plastoquinone, and rhodoquinone
in aqueous solution.
AB - Quinones can accept two electrons and two protons, and are involved in electron
transfer and proton transfer reactions in photosynthetic reaction centers. To
date, the pK a of these quinones in aqueous solution have not been reported. We
calculated the pK a of the initial protonation (Q.- to QH.) and the second
protonation (QH- to QH2) of 1,4-quinones using a quantum chemical approach. The
calculated energy differences of the protonation reactions Q.- to QH. and QH- to
QH2 in the aqueous phase for nine 1,4-quinones were highly correlated with the
experimentally measured pK a(Q.-/QH.) and pK a(QH-/QH2), respectively. In the
present study, we report the pK a(Q.-/QH.) and pK a(QH-/QH2) of ubiquinone,
menaquinone, phylloquinone, plastoquinone, and rhodoquinone in aqueous solution.
PMID- 28405862
TI - Isolation and characterization of PSI-LHCI super-complex and their sub-complexes
from a red alga Cyanidioschyzon merolae.
AB - Photosystem I (PSI)-light-harvesting complex I (LHCI) super-complex and its sub
complexes PSI core and LHCI, were purified from a unicellular red alga
Cyanidioschyzon merolae and characterized. PSI-LHCI of C. merolae existed as a
monomer with a molecular mass of 580 kDa. Mass spectrometry analysis identified
11 subunits (PsaA, B, C, D, E, F, I, J, K, L, O) in the core complex and three
LHCI subunits, CMQ142C, CMN234C, and CMN235C in LHCI, indicating that at least
three Lhcr subunits associate with the red algal PSI core. PsaG was not found in
the red algae PSI-LHCI, and we suggest that the position corresponding to Lhca1
in higher plant PSI-LHCI is empty in the red algal PSI-LHCI. The PSI-LHCI complex
was separated into two bands on native PAGE, suggesting that two different
complexes may be present with slightly different protein compositions probably
with respective to the numbers of Lhcr subunits. Based on the results obtained, a
structural model was proposed for the red algal PSI-LHCI. Furthermore, pigment
analysis revealed that the C. merolae PSI-LHCI contained a large amount of
zeaxanthin, which is mainly associated with the LHCI complex whereas little
zeaxanthin was found in the PSI core. This indicates a unique feature of the
carotenoid composition of the Lhcr proteins and may suggest an important role of
Zea in the light-harvesting and photoprotection of the red algal PSI-LHCI
complex.
PMID- 28405863
TI - High light acclimation of Chromera velia points to photoprotective NPQ.
AB - It has previously been shown that the long-term treatment of Arabidopsis thaliana
with the chloroplast inhibitor lincomycin leads to photosynthetic membranes
enriched in antennas, strongly reduced in photosystem II reaction centers (PSII)
and with enhanced nonphotochemical quenching (NPQ) (Belgio et al. Biophys J
102:2761-2771, 2012). Here, a similar physiological response was found in the
microalga Chromera velia grown under high light (HL). In comparison to cells
acclimated to low light, HL cells displayed a severe re-organization of the
photosynthetic membrane characterized by (1) a reduction of PSII but similar
antenna content; (2) partial uncoupling of antennas from PSII; (3) enhanced NPQ.
The decrease in the number of PSII represents a rather unusual acclimation
response compared to other phototrophs, where a smaller PSII antenna size is more
commonly found under high light. Despite the diminished PSII content, no net
damage could be detected on the basis of the Photosynthesis versus irradiance
curve and electron transport rates pointing at the excess capacity of PSII. We
therefore concluded that the photoinhibition is minimized under high light by a
lower PSII content and that cells are protected by NPQ in the antennas.
PMID- 28405864
TI - G-CSF and stem cell therapy for the treatment of refractory thin lining in
assisted reproductive technology.
AB - PURPOSE: The study aims to describe two promising therapeutic options for
resistant "thin" endometrium in fertility treatment: granulocyte colony
stimulating factor (G-CSF) and stem cell therapy. METHODS: A review of the
scientific literature related to patients with thin endometrium undergoing
fertility treatment. RESULTS: Sufficient endometrial growth is fundamental for
embryo implantation. Whether idiopathic or resulting from an underlying
pathology, a thin endometrium of <7 mm is associated with lower probability of
pregnancy; however, no specific thickness excludes the occurrence of pregnancy.
We specifically reviewed two relatively new treatment options for resistant thin
lining: intrauterine G-CSF and stem cell therapy. The majority of the reviewed
trials showed a significant benefit for intrauterine G-CSF infusion in improving
endometrial thickness and pregnancy rates. Early results of stem cell therapy
trials seem promising. CONCLUSIONS: EMT <7 mm is linked to lower probability of
pregnancy in assisted reproductive technology. Intrauterine G-CSF infusion
appears to be a potentially successful treatment option for resistant cases,
while stem cell therapy seems to be a promising new treatment modality in
severely refractory cases.
PMID- 28405865
TI - Involvement of 17beta-hydroxysteroid dehydrogenase type gene 1 937 A>G
polymorphism in infertility in Polish Caucasian women with endometriosis.
AB - PURPOSE: Endometriosis is considered to be an estrogen-related chronic
inflammatory disease. The 17beta-hydroxysteroid dehydrogenase 1 (HSD17B1)
converts estrone to 17beta estradiol. The role of HSD17B1 937 A>G (rs605059)
single nucleotide polymorphism (SNP) in development of endometriosis is still
disputable. This study evaluated the association of the HSD17B1 937 A>G
(rs605059) SNP with infertile women affected by endometriosis from Polish
Caucasian population. METHODS: The genotyping of cases (n = 290) and fertile
women (n = 410) was conducted by high-resolution melting curve analysis. RESULTS:
Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with
endometriosis in stages I and II. The p trend and p allelic values calculated for
the HSD17B1 937 A>G polymorphism were statistically significant and were equal to
0.001 and 0.0009, respectively. There was a significant association for the
dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178-3.304), p = 0.009, and
for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178-2.770), p =
0.006. However, we did not find statistical association of HSD17B1 937 A>G
polymorphism with all infertile women with endometriosis or infertile women with
endometriosis in stages III and IV. CONCLUSION: Our genetic study demonstrated
HSD17B1 937 G variant as a risk factor for infertility in women with stage I and
II endometriosis in Polish Caucasian patients.
PMID- 28405866
TI - Ethnoveterinary health management practices using medicinal plants in South Asia
a review.
AB - Animal rearing is the major occupation of most population of South Asian
countries. Due to lack of resources and limited approach to modern medicine, most
of the livestock raisers prefer to use plant-based traditional medicine also
referred to as ethnoveterinary medicine (EVM). Indeed, the use of medicinal
plants in South Asia dates back to several centuries with documented evidences.
However, there is currently a dearth of documentation and compilation of use of
medicinal plants for animal diseases in this part of the world. This review aims
to provide an up-to-date compilation of common medicinal plants used for the
treatment and/or management of common animal diseases in South Asian countries.
Extensive literature search was conducted online and relevant data was retrieved
from well-known scientific databases. A total of 276 plants belonging to 95
families have been documented to be in common use for managing 14 different
categories of animal diseases. Solanaceae, Lamiaceae, Fabaceae, and Leguminosae
were most common plant families in terms of their plant species used for EVM.
Gastric diseases were commonly reported and accounted for 72 species of plants
used for its treatment followed by the miscellaneous disorders category and skin
diseases comprising of 65 and 39 plant species respectively. Herbs accounted for
46% of the total plant species, followed by trees (33%), and shrubs (18%). The
EVM were applied through different routes of administration; oral administration
accounted for 72% followed by topical application 27%, while burning of plant
parts to create smoke around animals to repel insects was less common (1%). It is
anticipated that the present review will stimulate further ethnoveterinary
research among livestock disease management practices in South Asia.
PMID- 28405868
TI - Droplet-based non-faradaic impedance sensors for assessment of susceptibility of
Escherichia coli to ampicillin in 60 min.
AB - Direct antibiotic susceptibility tests (AST) are essential for rapid detection of
bacterial infection and administration of appropriate antibiotics. Conventional
AST systems are usually slow as they rely on cell growth for an indirect
assessment of antibiotics' effectiveness. Therefore, a faster method is
desirable, especially for emergency cases. In this work, we studied the
performance of label-free, droplet-based impedance sensors for rapid
characterization of the effects of ampicillin (Amp) on Escherichia coli.
Ampicillin damages cell wall integrity and makes cells permeable (leaky). The
leakage results in significant increase of the electrical conductance measured
directly by the microfabricated sensing unit. We studied the conductance signal
as a function of both antibiotic treatment time and dosage and demonstrated
susceptibility testing within 60 min. These findings demonstrate the potential of
droplet-based electrical chips for the realization of electrical antibiotic
susceptibility testing (e-AST) for early-stage diagnostic/treatment, and
consequently, preventing antibiotic misuse/overuse.
PMID- 28405867
TI - Low serum magnesium levels are associated with increased risk of fractures: a
long-term prospective cohort study.
AB - Magnesium, which is an essential trace element that plays a key role in several
cellular processes, is a major component of bone; however, its relationship with
risk of major bone fractures is uncertain. We aimed to investigate the
association of baseline serum magnesium concentrations with risk of incident
fractures. We analyzed data on 2245 men aged 42-61 years in the Kuopio Ischemic
Heart Disease prospective cohort study, with the assessment of serum magnesium
measurements and dietary intakes made at baseline. Hazard ratios [95% confidence
intervals (CI)] for incident total (femoral, humeral, and forearm) and femoral
fractures were assessed. During a median follow-up of 25.6 years, 123 total
fractures were recorded. Serum magnesium was non-linearly associated with risk of
total fractures. In age-adjusted Cox regression analysis, the hazard ratio (HR)
(95% CIs) for total fractures in a comparison of the bottom quartile versus top
quartile of magnesium concentrations was 2.10 (1.30-3.41), which persisted on
adjustment for several established risk factors 1.99 (1.23-3.24). The association
remained consistent on further adjustment for renal function, socioeconomic
status, total energy intake, and several trace elements 1.80 (1.10-2.94). The
corresponding adjusted HRs for femoral fractures were 2.56 (1.38-4.76), 2.43
(1.30-4.53) and 2.13 (1.13-3.99) respectively. There was no evidence of an
association of dietary magnesium intake with risk of any fractures. In middle
aged Caucasian men, low serum magnesium is strongly and independently associated
with an increased risk of fractures. Further research is needed to assess the
potential relevance of serum magnesium in the prevention of fractures.
PMID- 28405869
TI - Long-term neuropsychological follow-up of young children with medulloblastoma
treated with sequential high-dose chemotherapy and irradiation sparing approach.
AB - High-dose chemotherapy (HDC) strategies were developed in brain tumor protocols
for young children to prevent neuropsychological (NP) impairments associated with
radiotherapy. However, comprehensive NP evaluations of these children treated
with such strategies remain limited. We examined the long-term neurocognitive
outcomes of young children (<6 years) with medulloblastoma, treated similarly,
with a HDC strategy "according to" the chemotherapy regimen of the protocol CCG
99703. This retrospective study included young children less than 6 years of age
at diagnosis of medulloblastoma treated from 1998 to 2011 at 7 North American
institutions. Twenty-four patients who had at least one NP assessment post
treatment are the focus of the current study. Of 24 patients in this review, 15
(63%) were male and the mean age at diagnosis was 29.4 months (SD = 13.5).
Posterior fossa syndrome (PFs) was reported in five patients (21%). Nine (37.5%)
received radiotherapy (5 focal, 4 craniospinal). On average, children were
assessed 3.5 years (SD = 1.8) post-diagnosis, and full-scale intellectual
quotient (FSIQ) scores ranged from 56 to 119 ([Formula: see text]= 92; SD =
16.8). The majority of children (74%) had low-average to average NP functioning.
Very young children treated with radiotherapy, who needed hearing support or with
PFs had worse neurocognitive outcomes. Clinically significant deficits (<10th
percentile) in at least one area of NP functioning were found in 25% of the
children. NP data obtained from this sample of survivors of medulloblastoma in
early childhood, all treated with sequential HDC and 1/3 with radiotherapy,
describe NP functioning within average normal limits overall. However, almost 25%
of children had significant deficits in specific domains.
PMID- 28405870
TI - The effect of temperature on the resting and post-exercise metabolic rates and
aerobic metabolic scope in shortnose sturgeon Acipenser brevirostrum.
AB - The effects of acclimation temperature (15, 20, 25 degrees C) on routine oxygen
consumption and post-exercise maximal oxygen consumption rates (MO2) were
measured in juvenile shortnose sturgeon (Acipenser brevirostrum LeSueur, 1818).
The routine MO2 of shortnose sturgeon increased significantly from 126.75 mg O2 h
1 kg-1 at 15 degrees C to 253.13 mg O2 h-1 kg-1 at 25 degrees C. The
temperature coefficient (Q 10) values of the routine metabolic rates ranged
between 1.61 and 2.46, with the largest Q 10 values occurring between 15 and 20
degrees C. The average post-exercise MO2 of all temperature groups increased to a
peak value immediately following the exercise, with levels increasing about 2
fold among all temperature groups. The Q 10 values for post-exercise MO2 ranged
from 1.21 to 2.12, with the highest difference occurring between 15 and 20
degrees C. Post-exercise MO2 values of shortnose sturgeon in different
temperature groups all decreased exponentially and statistically returned to pre
exercise (resting) levels by 30 min at 15 and 20 degrees C and by 60 min at 25
degrees C. The aerobic metabolic scope (post-exercise maximal MO2-routine MO2)
increased to a maximum value ~156 mg O2 h-1 kg-1 at intermediate experimental
temperatures (i.e., 20 degrees C) and then decreased as the temperature
increased to 25 degrees C. However, this trend was not significant. The results
suggest that juvenile shortnose sturgeon show flexibility in their ability to
adapt to various temperature environments and in their responses to exhaustive
exercise.
PMID- 28405871
TI - Racial/Ethnic Differences in Those Accompanying Medicare Patients to the Doctor:
Insights from the 2013 Medicare Current Beneficiary's Survey.
AB - Surprisingly little current, population-level detail exists regarding companion
accompaniment for health care among Medicare beneficiaries, particularly by
race/ethnicity. For respondents in the 2013 Medicare Current Beneficiary's Survey
Access to Care public use data (N = 12,253), multivariable models predicted
accompaniment to the doctor by race/ethnicity, adjusting for confounders. Chi
square analyses compared, by race/ethnicity, who was accompanying and why.
Overall, 37.5% of beneficiaries had accompaniment. In multivariable analyses, non
Hispanic blacks (OR 1.18; 95% CI 1.03-1.36) and Hispanics (OR 1.47; 95% CI 1.25
1.74) were significantly more likely than non-Hispanic whites to have
accompaniment. Over 35% of all three groups had someone to "take notes," "ask
questions," and/or "explain things," which did not vary by race/ethnicity;
significant differences were seen for "explain instructions," "translate," and
"moral support." Hispanics had the highest percentages for all three. Many
Medicare beneficiaries have accompaniment to doctors' appointments, particularly
in minority racial/ethnic groups, which should be considered in policy and
practice.
PMID- 28405872
TI - A novel method for assessment of local pH in periplasmic space and of cell
surface potential in yeast.
AB - Yeast cells exhibit a negative surface potential due to negative charges at the
cell membrane surface. Consequently, local concentrations of cations at the
periplasmic membrane surface may be significantly increased compared to their
bulk environment. However, in cell suspensions only bulk concentrations of
cations can be measured directly. Here we present a novel method enabling the
assessment of local pH at the periplasmic membrane surface which can be directly
related to the underlying cell surface potential. In this proof of concept study
using Saccharomyces cerevisiae cells with episomally expressed pH reporter,
pHluorin, intracellular acidification induced by the addition of the protonophore
carbonyl cyanide m-chlorophenylhydrazone (CCCP) was measured using synchronously
scanned fluorescence spectroscopy (SSF). The analysis of titration curves
revealed that the pH at the periplasmic surface of S. cerevisiae cells was about
two units lower than the pH of bulk medium. This pH difference was significantly
decreased by increasing the ionic strength of the bulk medium. The cell surface
potential was estimated to amount to -130 mV. Comparable results were obtained
also with another protonophore, pentachlorophenol (PCP).
PMID- 28405873
TI - Erratum to: Robotic radical cystectomy: technical tips and tricks.
PMID- 28405874
TI - Systemic Inflammation during the First Postnatal Month and the Risk of Attention
Deficit Hyperactivity Disorder Characteristics among 10 year-old Children Born
Extremely Preterm.
AB - Although multiple sources link inflammation with attention difficulties, the only
human study that evaluated the relationship between systemic inflammation and
attention problems assessed attention at age 2 years. Parent and/or teacher
completion of the Childhood Symptom Inventory-4 (CSI-4) provided information
about characteristics that screen for attention deficit hyperactive disorder
(ADHD) among 793 10-year-old children born before the 28th week of gestation who
had an IQ >= 70. The concentrations of 27 proteins in blood spots obtained during
the first postnatal month were measured. 151 children with ADHD behaviors were
identified by parent report, while 128 children were identified by teacher
report. Top-quartile concentrations of IL-6R, TNF-alpha, IL-8, VEGF, VEFG-R1, and
VEGF-R2 on multiple days were associated with increased risk of ADHD symptoms as
assessed by a teacher. Some of this increased risk was modulated by top-quartile
concentrations of IL-6R, RANTES, EPO, NT-4, BDNF, bFGF, IGF-1, PIGF, Ang-1, and
Ang-2. Systemic inflammation during the first postnatal month among children born
extremely preterm appears to increase the risk of teacher-identified ADHD
characteristics, and high concentrations of proteins with neurotrophic properties
appear capable of modulating this increased risk.
PMID- 28405875
TI - Acute Fasting Induces Expression of Acylglycerophosphate Acyltransferase (AGPAT)
Enzymes in Murine Liver, Heart, and Brain.
AB - During fasting, cells increase uptake of non-esterified fatty acids (NEFA) and
esterify excess into phosphatidic acid (PtdOH), the common precursor of both
triacylglycerols and phospholipids, using acylglycerophosphate
acyltransferases/lysophosphatidic acid acyltransferases (AGPAT/LPAAT). Knowledge
of the regulation of AGPAT enzymes is important for understanding fasting
adaptations. Total RNA was isolated from liver, heart, and whole brain tissue of
C57BL/6J mice fed ad libitum, or fasted for 16 h. Following fasting, induction of
Agpat2, 3, 4, and 5 was observed in the liver, Agpat2 and 3 in heart tissue, and
Agpat1, 2, and 3 in whole brain tissue. As a result, the relative abundance
profile of the individual homologues within specific tissues was found to be
significantly altered depending on the nutritive state of the animal. These data
demonstrate tissue-specific effects of fasting on the regulation of different
Agpat that are implicated in supporting unique downstream glycerolipid synthesis
pathways.
PMID- 28405876
TI - Laparoscopic Sleeve Gastrectomy in Kidney Transplant Candidates: a Case Series.
AB - BACKGROUND: Patients with a body mass index (BMI) >35 kg/m2 who need kidney
transplant present with increased postoperative mortality and reduced kidney
graft survival compared to patients with a lower BMI. For this reason, obese
patients are often excluded from the transplantation waiting list. The aim of
this study was to evaluate the feasibility and the results of laparoscopic sleeve
gastrectomy (LSG) for obese patients awaiting a kidney transplant. METHODS: This
was a retrospective study on patients with dialysis-dependent renal failure
(DDRF) operated on at two first-level bariatric centers in Paris (France). All
the patients were contraindicated for kidney transplantation due to the presence
of morbid obesity. RESULTS: Nine DDFR patients with a mean BMI of 45.9 kg/m2
underwent LSG for the treatment of obesity. Furthermore, all patients presented
with hypertension and sleep apnea and six out nine were diabetics. In the
immediate postoperative period, all patients were transferred to the intensive
care unit (mean stay of 2.1 days). The only major adverse event was a delayed
weaning from mechanical ventilation in one patient. The mean hospital stay was
5.5 days (3-12). The total weight loss (TWL) was 27.1, 33.6, and 39.5 kg at 6,
12, and 18 months, respectively. One patient underwent renal transplantation 18
months after LSG, and the other five patients were actively listed for kidney
transplantation. CONCLUSIONS: According to the results of this small sample
series, LSG seems to be an effective and safe procedure in DDRF patients with
concomitant obesity and can increase access to transplantation.
PMID- 28405877
TI - Revision Roux-en-Y Gastric Bypass to Biliopancreatic Long-Limb Gastric Bypass for
Inadequate Weight Response: Case Series and Analysis.
AB - BACKGROUND: The long-limb Roux-en-Y gastric bypass (LLRYGB) was introduced in
1987 as a salvage operation for inadequate weight loss after a standard Roux-en-Y
gastric bypass (RYGB). METHODS: We report on 53 consecutive patients (44 females)
with conversion of a failed RYGB to a LLRYGB performed by a single surgeon
between 2002 and 2014. No patient had an ascertainable anatomic abnormality to
explain his/her weight regain. LLRYGB revision consisted of a 75-cm to 100-cm
alimentary Roux limb and a 75-cm to 100-cm common channel; after 2011, in
suitable patients, the Roux limb was lengthened to greater than 250 cm. RESULTS:
Average values for weight (lbs) were as follows: pre-original RYGB = 329; lowest
measured after RYGB = 196; at time of LLRYGB = 285; and at 1, 2, 3, 4, >5 years
post LLRYGB = 225, 207, 199, 197, 195, for a sustained weight loss >90 lbs.
Average values for BMI (kg/m2) were as follows: pre-original RYGB = 54.3; lowest
measured after RYGB = 32.3; at time of LLRYGB = 47.2; and at 1, 2, 3, 4, >5 years
post LLRYGB = 37.1, 34.4, 33.0, 32.8, 31.4, for a sustained BMI reduction >16.5
kg/m2. Zero operative mortality; 3 (5.7%) late deaths; 7 (13.2%) 30-day
complications; 33 (62.3%) long-term complications with 23 (43.4%) needing TPN;
and 14 (26.4%) requiring operative revision. CONCLUSION: A salvage LLRYGB
procedure can be performed safely and is weight successful, but fraught with long
term nutritional problems and a high necessity for revision. A Roux segment over
250 cm may improve outcomes.
PMID- 28405878
TI - Bariatric Surgery and Endoluminal Procedures: IFSO Worldwide Survey 2014.
AB - BACKGROUND AND AIM: Several bariatric surgery worldwide surveys have been
previously published to illustrate the evolution of bariatric surgery in the last
decades. The aim of this survey is to report an updated overview of all bariatric
procedures performed in 2014.For the first time, a special section on endoluminal
techniques was added. METHODS: The 2014 International Federation for the Surgery
of Obesity and Metabolic Disorders (IFSO) survey form evaluating the number and
the type of surgical and endoluminal bariatric procedures was emailed to all IFSO
societies. Trend analyses from 2011 to 2014 were also performed. RESULTS: There
were 56/60 (93.3%) responders. The total number of bariatric/metabolic procedures
performed in 2014 consisted of 579,517 (97.6%) surgical operations and 14,725
(2.4%) endoluminal procedures. The most commonly performed procedure in the world
was sleeve gastrectomy (SG) that reached 45.9%, followed by Roux-en-Y gastric
bypass (RYGB) (39.6%), and adjustable gastric banding (AGB) (7.4%). The annual
percentage changes from 2013 revealed the increase of SG and decrease of RYGB in
all the IFSO regions (USA/Canada, Europe, and Asia/Pacific) with the exception of
Latin/South America, where SG decreased and RYGB represented the most frequent
procedure. CONCLUSIONS: There was a further increase in the total number of
bariatric/metabolic procedures in 2014 and SG is currently the most frequent
surgical procedure in the world. This is the first survey that describes the
endoluminal procedures, but the accuracy of provided data should be hopefully
improved in the next future. We encourage the creation of further national
registries and their continuous updates taking into account all new bariatric
procedures including the endoscopic procedures that will obtain increasing
importance in the near future.
PMID- 28405879
TI - Histopathological and genetic characterization of aldosterone-producing adenomas
with concurrent subclinical cortisol hypersecretion: a case series.
AB - PURPOSE: Aldosterone-producing adenomas with concurrent subclinical cortisol
hypersecretion are reported in an increasing number of patients. Five aldosterone
producing adenomas from patients with primary aldosteronism and subclinical
hypercortisolism were examined. THE AIMS OF OUR STUDY WERE: (1) to analyze
pathological features and immunohistochemical expression of CYP11B1 (11beta
hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to
investigate somatic mutations involved in adrenal steroid hypersecretion and/or
tumor growth. METHODS: Archival micro-dissected paraffin-embedded slides from
tumor specimens were used for histological and molecular studies.
Immunohistochemistry was performed using monoclonal anti-CYP11B1 and anti-CYP11B2
antibodies. Cellular composition was determined by examining for known features
of zona fasciculata and zona glomerulosa, and immunoreactivity for CYP11B1 and
CYP11B2 by McCarty H-score. Spot regions for mutations in KCNJ5, ATP1A1, ATP2B3,
CACNA1D, PRKACA, and CTNNB1 gene sequences were evaluated. RESULTS: Four APAs
showed a predominant (>=50%) zona fasciculata-like cell pattern: one tumor had
CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACA
p.Leu206Arg mutation (that we have reported previously elsewhere), one had no
CYP11B1 expression, CYP11B2 H-score = 40, and no mutations; the remaining two
adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H
score (30 and 15, respectively), with the latter harboring a CTNNB1 p.Ser45Phe
activating mutation. One of five aldosterone-producing adenomas had a predominant
zona glomerulosa-like pattern, CYP11B1 H-score = 15, CYP11B2 H-score = 180, and
no mutations. CONCLUSIONS: The majority of aldosterone-producing adenomas with
concurrent subclinical cortisol hypersecretion were composed mainly of zona
fasciculata-like cells, while CYP11B1 and CYP11B2 immunostaining demonstrated
clear heterogeneity. In a subset of cases, different somatic mutations may be
involved in hormone excess and tumor formation.
PMID- 28405880
TI - STEAP4 expression in human islets is associated with differences in body mass
index, sex, HbA1c, and inflammation.
AB - OBJECTIVE: STEAP4 (six-transmembrane epithelial antigen of the prostate 4) is a
metalloreductase that has been shown previously to protect cells from
inflammatory damage. Genetic variants in STEAP4 have been associated with
numerous metabolic disorders related to obesity, including putative defects in
the acute insulin response to glucose in type 2 diabetes. PURPOSE: We examined
whether obesity and/or type 2 diabetes altered STEAP4 expression in human
pancreatic islets. METHODS: Human islets were isolated from deceased donors at
two medical centers and processed for quantitative polymerase chain reaction.
Organ donors were selected by status as non-diabetic or having type 2 diabetes.
Site 1 (Edmonton): N = 13 type 2 diabetes donors (7M, 6F), N = 20 non-diabetic
donors (7M, 13F). Site 2 (Virginia): N = 6 type 2 diabetes donors (6F), N = 6 non
diabetic donors (3M, 3F). RESULTS: STEAP4 showed reduced islet expression with
increasing body mass index among all donors (P < 0.10) and non-diabetic donors (P
< 0.05) from Site 1; STEAP4 showed reduced islet expression among type 2 diabetes
donors with increasing hemoglobin A1c. Islet STEAP4 expression was also
marginally higher in female donors (P < 0.10). Among type 2 diabetes donors from
Site 2, islet insulin expression was reduced, STEAP4 expression was increased,
and white blood cell counts were increased compared to non-diabetic donors.
Islets from non-diabetic donors that were exposed overnight to 5 ng/ml IL-1beta
displayed increased STEAP4 expression, consistent with STEAP4 upregulation by
inflammatory signaling. CONCLUSIONS: These findings suggest that increased STEAP4
mRNA expression is associated with inflammatory stimuli, whereas lower STEAP4
expression is associated with obesity in human islets. Given its putative
protective role, downregulation of STEAP4 by chronic obesity suggests a mechanism
for reduced islet protection against cellular damage.
PMID- 28405882
TI - IQ-SPECT for thallium-201 myocardial perfusion imaging: effect of normal
databases on quantification.
AB - OBJECTIVE: Although IQ-single-photon emission computed tomography (SPECT)
provides rapid acquisition and attenuation-corrected images, the unique
technology may create characteristic distribution different from the conventional
imaging. This study aimed to compare the diagnostic performance of IQ-SPECT using
Japanese normal databases (NDBs) with that of the conventional SPECT for thallium
201 (201Tl) myocardial perfusion imaging (MPI). METHODS: A total of 36 patients
underwent 1-day 201Tl adenosine stress-rest MPI. Images were acquired with IQ
SPECT at approximately one-quarter of the standard time of conventional SPECT.
Projection data acquired with the IQ-SPECT system were reconstructed via an
ordered subset conjugate gradient minimizer method with or without scatter and
attenuation correction (SCAC). Projection data obtained using the conventional
SPECT were reconstructed via a filtered back projection method without SCAC. The
summed stress score (SSS) was calculated using NDBs created by the Japanese
Society of Nuclear Medicine working group, and scores were compared between IQ
SPECT and conventional SPECT using the acquisition condition-matched NDBs. The
diagnostic performance of the methods for the detection of coronary artery
disease was also compared. RESULTS: SSSs were 6.6 +/- 8.2 for the conventional
SPECT, 6.6 +/- 9.4 for IQ-SPECT without SCAC, and 6.5 +/- 9.7 for IQ-SPECT with
SCAC (p = n.s. for each comparison). The SSS showed a strong positive correlation
between conventional SPECT and IQ-SPECT (r = 0.921 and p < 0.0001), and the
correlation between IQ-SPECT with and without SCAC was also good (r = 0.907 and p
< 0.0001). Regarding diagnostic performance, the sensitivity, specificity, and
accuracy were 80.8, 78.9, and 79.4%, respectively, for the conventional SPECT;
80.8, 80.3, and 82.0%, respectively, for IQ-SPECT without SCAC; and 88.5, 86.8,
and 87.3%, respectively, for IQ-SPECT with SCAC, respectively. The area under the
curve obtained via receiver operating characteristic analysis were 0.77, 0.80,
and 0.86 for conventional SPECT, IQ-SPECT without SCAC, and IQ-SPECT with SCAC,
respectively (p = n.s. for each comparison). CONCLUSIONS: When appropriate NDBs
were used, the diagnostic performance of 201Tl IQ-SPECT was comparable with that
of the conventional system regardless of different characteristics of myocardial
accumulation in the conventional system.
PMID- 28405881
TI - Accuracy of recommended sampling and assay methods for the determination of
plasma-free and urinary fractionated metanephrines in the diagnosis of
pheochromocytoma and paraganglioma: a systematic review.
AB - PURPOSE: To determine the accuracy of biochemical tests for the diagnosis of
pheochromocytoma and paraganglioma. METHODS: A search of the PubMed database was
conducted for English-language articles published between October 1958 and
December 2016 on the biochemical diagnosis of pheochromocytoma and paraganglioma
using immunoassay methods or high-performance liquid chromatography with
coulometric/electrochemical or tandem mass spectrometric detection for
measurement of fractionated metanephrines in 24-h urine collections or plasma
free metanephrines obtained under seated or supine blood sampling conditions.
RESULTS: Application of the Standards for Reporting of Diagnostic Studies
Accuracy Group criteria yielded 23 suitable articles. Summary receiver operating
characteristic analysis revealed sensitivities/specificities of 94/93% and 91/93%
for measurement of plasma-free metanephrines and urinary fractionated
metanephrines using high-performance liquid chromatography or immunoassay
methods, respectively. Partial areas under the curve were 0.947 vs. 0.911.
Irrespective of the analytical method, sensitivity was significantly higher for
supine compared with seated sampling, 95 vs. 89% (p < 0.02), while specificity
was significantly higher for supine sampling compared with 24-h urine, 95 vs. 90%
(p < 0.03). Partial areas under the curve were 0.942, 0.913, and 0.932 for supine
sampling, seated sampling, and urine. Test accuracy increased linearly from 90 to
93% for 24-h urine at prevalence rates of 0.0-1.0, decreased linearly from 94 to
89% for seated sampling and was constant at 95% for supine conditions.
CONCLUSIONS: Current tests for the biochemical diagnosis of pheochromocytoma and
paraganglioma show excellent diagnostic accuracy. Supine sampling conditions and
measurement of plasma-free metanephrines using high-performance liquid
chromatography with coulometric/electrochemical or tandem mass spectrometric
detection provides the highest accuracy at all prevalence rates.
PMID- 28405883
TI - Obstructive sleep apnea syndrome and public health: the Italian way.
PMID- 28405884
TI - Response to "regarding the sudden death of a juvenile with rare TdT-negative T
LBL/T-ALL, splenic rupture, and mediastinal mass".
PMID- 28405885
TI - Sudden death due to catecholaminergic polymorphic ventricular tachycardia
following negative stress-test outcome: genetics and clinical implications.
AB - This paper discusses the case of a young boy who died suddenly during a football
match. The victim's personal and family medical histories were negative for
cardiac events. He had undergone a cardiological investigation some months before
his death, enabling him to participate in competitive sports. Only post-mortem
molecular analysis allowed for a clearer determination of the most plausible
cause of death, which was identified as inherited arrhythmogenic heart disease,
known as catecholaminergic polymorphic ventricular tachycardia. It was possible
to detect a novel, previously undescribed, variant in the RYR2 gene. This case
report highlights the importance of a meaningful forensic multidisciplinary
investigation in such cases, and also discusses possible medical malpractice
claims.
PMID- 28405887
TI - Renal Cell Carcinoma Metastatic to the Gallbladder.
PMID- 28405888
TI - Effects of common GRM5 genetic variants on cognition, hippocampal volume and
mGluR5 protein levels in schizophrenia.
AB - GRM5 (coding for metabotropic glutamate receptor 5, mGluR5) is a promising target
for the treatment of cognitive deficits in schizophrenia, but there has been
little investigation of its association with cognitive and brain phenotypes
within this disorder. We examined the effects of common genetic variation in GRM5
with cognitive function, hippocampal volume, and hippocampal mGluR5 protein
levels in schizophrenia patients relative to healthy controls. Two independent
GRM5 variants rs60954128 [C>T] and rs3824927 [G>T] were genotyped in a
schizophrenia case/control cohort (n=249/261). High-resolution anatomical brain
scans were available for a subset of the cohort (n=103 schizophrenia /78
control). All participants completed a standard set of neuropsychological tests.
In a separate postmortem cohort (n=19 schizophrenia/20 controls), hippocampal
mGluR5 protein levels were examined among individuals of different GRM5
genotypes. Schizophrenia minor allele carriers of rs60954128 had reduced right
hippocampal volume relative to healthy controls of the same genotype (-12.3%);
this effect was exaggerated in males with schizophrenia (-15.6%). For rs3824927,
compared to major allele homozygotes, minor allele carriers with schizophrenia
had lower Intelligence Quotients (IQ). Examination in hippocampal postmortem
tissue showed no difference in mGluR5 protein expression according to genotype
for either rs60954128 or rs3824927. While these genetic variants in GRM5 were
associated with cognitive impairments and right hippocampal volume reduction in
schizophrenia, they did not affect protein expression. Further study of these
mechanisms may help to delineate new targets for the treatment of cognitive
deficits in schizophrenia, and may be relevant to other disorders.
PMID- 28405889
TI - Asymptotic Expansion Method with Respect to Small Parameter for Ternary Diffusion
Models.
AB - Ternary diffusion models lead to strongly coupled systems of PDEs. We choose the
smallest diffusion coefficient as a small parameter in a power series expansion
whose components fulfill relatively simple equations. Although this series is
divergent, one can use its finite sums to derive feasible numerical
approximations, e.g. finite difference methods (FDMs).
PMID- 28405890
TI - Seroprevalence of Bartonella Species in Patients with Ocular Inflammation.
AB - Bartonella species, vector-borne etiologic agents of many systemic or self
limited infections, are responsible for a widening spectrum of diseases in
humans, including inflammatory conditions of the eye. The aim of this study was
to determine whether there is any relationship between uveitis and the evidence
of Bartonella spp. infection in the serum, ocular fluid, and cataract mass in
patients with intraocular inflammation. Polymerase chain reaction (PCR)-based
tests and DNA sequencing were performed on surgery-extracted specimens of
intraocular fluid and lens mass of 33 patients. Sera from 51 patients and 101
control subjects were tested for the presence of specific antibodies against
Bartonella spp. Neither IgM-class antibodies against Bartonella spp. nor
Bartonella spp. DNA were detected. A specific IgG-class antibody was found in
33.3% of the patients with uveitis. The rate of positive Bartonella serology was
higher among the uveitis patients than that in control subjects. This high rate
may in part result from unrecognized indirect mechanisms rather than the
immediate presence and multiplication of Bartonella spp. in the eyeball.
Nonetheless we believe that screening for Bartonella spp. should become part of
the diagnostic workup in uveitis.
PMID- 28405891
TI - Renalase in Children with Glomerular Kidney Diseases.
AB - Studies suggest that renalase, a renal catecholamine-inactivating enzyme, plays a
major role in the pathogenesis of kidney and cardiovascular diseases in adults.
This study seeks to determine the role of renalase in children with glomerular
kidney diseases. We evaluated the serum renalase, arterial stiffness, intima
media thickness, blood pressure, and clinical and biochemical parameters in 78
children (11.9 +/- 4.6 years of age) with glomerulopathies such as idiopathic
nephrotic syndrome (40 cases), IgA nephropathy (12 cases), Henoch-Schonlein
nephropathy (12 cases), and other glomerulopathies (14 cases). The control group
consisted of 38 healthy children aged 11.8 +/- 3.3 years. The mean renalase was
25.74 +/- 8.94 MUg/mL in the glomerulopathy group, which was not significantly
different from the 27.22 +/- 5.15 in the control group. The renalase level did
not differ among various glomerulopathies either. However, proteinuric patients
had a higher renalase level than those without proteinuria (28.43 +/- 11.71 vs.
24.05 +/- 6.23, respectively; p = 0.03). In proteinuric patients, renalase
correlated with daily proteinuria. In the entire glomerulopathy group, renalase
correlated with age, systolic central blood pressure (BP), diastolic peripheral
and central BP, mean peripheral and central BP; peripheral diastolic BP Z-score,
glomerular filtration rate, cholesterol, triglycerides, and pulse wave velocity.
We conclude that in children with glomerulopathies renalase, although basically
not enhanced, may underlie blood pressure elevation and arterial damage.
PMID- 28405892
TI - Pro-inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents:
A Review.
AB - Cytokines are a large group of small proteins which play a significant role in
cell signaling and regulate a variety of processes in organisms, including
proliferation and differentiation of many cells, mediation in defense reactions
and regulation of hematopoiesis. Cytokines can be divided into those with pro-
and those with anti-inflammatory properties. In the group of pro-inflammatory
cytokines the most important are: IL-1 beta, IL-6, TNF-alpha, and IFN-gamma. Pro
inflammatory cytokines might be involved in the pathophysiology of many
psychiatric conditions in adults, but their role in children and adolescents is
less clear. The aim of this article is to demonstrate the patterns of pro
inflammatory cytokines in children and adolescents.
PMID- 28405886
TI - Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine.
AB - In this review, we evaluate the variability in the pharmacokinetics of 11 drugs
with established prophylactic effects in migraine to facilitate 'personalized
medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady
state' pharmacokinetic studies of these 11 drugs. The maximum plasma
concentration was reported in 248 single-dose and 115 steady-state
pharmacokinetic studies, and the area under the plasma concentration-time curve
was reported in 299 single-dose studies and 112 steady-state pharmacokinetic
studies. For each study, the coefficient of variation was calculated for maximum
plasma concentration and area under the plasma concentration-time curve, and we
divided the drug variability into two categories; high variability, coefficient
of variation >40%, or low or moderate variability, coefficient of variation <40%.
Based on the area under the plasma concentration-time curve in steady-state
studies, the following drugs have high pharmacokinetic variability: propranolol
in 92% (33/36), metoprolol in 85% (33/39), and amitriptyline in 60% (3/5) of
studies. The following drugs have low or moderate variability: atenolol in 100%
(2/2), valproate in 100% (15/15), topiramate in 88% (7/8), and naproxen and
candesartan in 100% (2/2) of studies. For drugs with low or moderate
pharmacokinetic variability, treatment can start without initial titration of
doses, whereas titration is used to possibly enhance tolerability of topiramate
and amitriptyline. The very high pharmacokinetic variability of metoprolol and
propranolol can result in very high plasma concentrations in a small minority of
patients, and those drugs should therefore be titrated up from a low initial
dose, depending mainly on the occurrence of adverse events.
PMID- 28405893
TI - Airway and Blood Inflammatory Markers in Waste Collectors.
AB - Waste collectors are exposed to a heterogeneous mixture of bioaerosols able to
induce health effects. The study aim was to evaluate inflammatory processes in
blood and in the respiratory tract via analysis of atopy and club cell secretory
protein 16 (CC16) in serum, exhaled nitric oxide (FeNO), and cellular and soluble
mediators in nasal lavage fluid (NALF) and induced sputum (IS). Sixty nine
current waste collectors (48% smokers) and 28 former waste collectors (25%
smokers) were included in the cross-sectional study. In both groups, 63 and 64%
of workers reported complaints of the eyes, nose and/or upper airways. Thirty two
percent of the current and 25% of the former workers were classified as atopics.
More atopics suffered from rhinitis and conjunctivitis than non-atopics (64% vs.
40% in current workers; 71% vs. 40% in former workers). CC16 values of present
non-smokers were significantly higher compared to smokers. In total, FeNO values
of 31 participants were lower than 10 ppb, 94% of them were smokers and 85% had
respiratory symptoms of lower airways. Most of the IS biomarkers were
significantly higher in smokers than in non-smokers. Non-smoking workers with
respiratory symptoms of lower airways had slightly elevated mediator IS
concentrations compared to asymptomatic non-smokers. We conclude that
inflammatory changes in waste collectors are detectable in the content of IS
biomarkers, exhaled NO, and serum CC16, which all are influenced by the smoking
habit. No significant differences in biomarkers are detectable between current
and former waste collectors.
PMID- 28405894
TI - Addressing the Needs of Children With Disabilities Experiencing Disaster or
Terrorism.
AB - PURPOSE OF REVIEW: This paper reviews the empirical literature on psychosocial
factors relating to children with disabilities in the context of disaster or
terrorism. RECENT FINDINGS: Research indicates adults with disabilities
experience increased exposure to hazards due to existing social disparities and
barriers associated with disability status. However, studies on the psychological
effects of disaster/terrorism on children with pre-existing disabilities are
exceedingly few and empirical evidence of the effectiveness of trauma-focused
therapies for this population is limited. Secondary adversities, including social
stigma and health concerns, also compromise the recovery of these children post
disaster/terrorism. Schools and teachers appear to be particularly important in
the recovery of children with disabilities from disaster. Disasters, terrorism,
and war all contribute to increased incidence of disability, as well as
disproportionately affect children with pre-existing disabilities. Disaster
preparedness interventions and societal changes are needed to decrease the
disproportionate environmental and social vulnerability of children with
disabilities to disaster and terrorism.
PMID- 28405895
TI - The Impact of Frequency and Tone of Parent-Youth Communication on Type 1 Diabetes
Management.
AB - BACKGROUND: The purpose of this study is to assess the impact of frequency and
tone of parent-youth communication on glycemic control as measured by the Family
Communication Inventory (FCI). Adolescence provides a unique set of diabetes
management challenges, including suboptimal glycemic control. Continued parental
involvement in diabetes management is associated with improved HbA1c outcomes;
however, diabetes-related conflict within the family can have adverse effects.
Although it is clear that communication plays an important role in diabetes
outcomes, the specific impact of frequency and tone of such communication is
largely understudied. METHODS: A total of 110 youths with type 1 diabetes and
their parents completed questionnaires assessing diabetes-related adherence,
family conflict, and family communication (i.e., frequency and tone) during a
routine clinic visit. Routine testing of HbA1c was performed. RESULTS: Youth- and
parent-reported frequency of communication were unrelated to HbA1c. Instead,
greater discrepancies between parents and children on reported frequency of
communication (most commonly parents reporting frequent and youth reporting less
frequent communication) corresponded with poorer glycemic control and increased
family conflict. More positive tone of communication as rated by youth was
associated with lower HbA1c. CONCLUSIONS: Diabetes-related communication is more
complex than conveyed simply by how often children and their parents communicate.
Tone of communication and discrepancies in a family's perception of the frequency
of communication were better than frequency as predictors of glycemic control.
The FCI appears to capture the frequency and tone of diabetes-related
communication, though larger-scale studies are warranted to inform future use of
this scale.
PMID- 28405897
TI - Culturally-Relevant Online Cancer Education Modules Empower Alaska's Community
Health Aides/Practitioners to Disseminate Cancer Information and Reduce Cancer
Risk.
AB - To address a desire for timely, medically accurate cancer education in rural
Alaska, ten culturally relevant online learning modules were developed with, and
for, Alaska's Community Health Aides/Practitioners (CHA/Ps). The project was
guided by the framework of Community-Based Participatory Action Research, honored
Indigenous Ways of Knowing, and was informed by Empowerment Theory. A total of
428 end-of-module evaluation surveys were completed by 89 unique Alaska CHA/Ps
between January and December 2016. CHA/Ps shared that as a result of completing
the modules, they were empowered to share cancer information with their patients,
families, friends, and communities, as well as engage in cancer risk reduction
behaviors such as eating healthier, getting cancer screenings, exercising more,
and quitting tobacco. CHA/Ps also reported the modules were informative and
respectful of their diverse cultures. These results from end-of-module evaluation
surveys suggest that the collaboratively developed, culturally relevant, online
cancer education modules have empowered CHA/Ps to reduce cancer risk and
disseminate cancer information. "brought me to tears couple of times, and I think
it will help in destroying the silence that surrounds cancer".
PMID- 28405896
TI - Integrating Personalized Technology in Toxicology: Sensors, Smart Glass, and
Social Media Applications in Toxicology Research.
AB - Rapid proliferation of mobile technologies in social and healthcare spaces create
an opportunity for advancement in research and clinical practice. The application
of mobile, personalized technology in healthcare, referred to as mHealth, has not
yet become routine in toxicology. However, key features of our practice
environment, such as frequent need for remote evaluation, unreliable historical
data from patients, and sensitive subject matter, make mHealth tools appealing
solutions in comparison to traditional methods that collect retrospective or
indirect data. This manuscript describes the features, uses, and costs associated
with several of common sectors of mHealth research including wearable biosensors,
ingestible biosensors, head-mounted devices, and social media applications. The
benefits and novel challenges associated with the study and use of these
applications are then discussed. Finally, opportunities for further research and
integration are explored with a particular focus on toxicology-based
applications.
PMID- 28405898
TI - Current Smokers' Preferences for Receiving Cessation Information in a Lung Cancer
Screening Setting.
AB - The purpose of this study was to identify current smokers' communication format
preferences for receiving smoking cessation information in a lung cancer
screening setting. A cross-sectional correlational design using survey
methodology with 159 screening-eligible current smokers was the method used. Data
was dichotomized (digital versus traditional preference) and analyzed using
Pearson's chi-squared test, Mann-Whitney U test, and logistic regression. Race
was a statistically significant predictor with White participants having four
times greater odds of reporting preference for a digital format for receiving
smoking cessation information such as social media and/or supportive text
messages (OR: 4.06; p = 0.004). Lung cancer screening is a new venue where
current long-term smokers can be offered information about smoking cessation
while they are engaging in a health-promoting behavior and potentially more
likely to contemplate quitting. It is important to consider the communication
format preference of current smokers to support cessation uptake. This study is
the first to examine communication format preference of current smokers in the
context of the lung cancer screening venue. Key differences noted by race support
the need for further research examining multiple formats of communication with
efforts to maximize options in the cancer screening setting.
PMID- 28405899
TI - The Quality of Clinical Information in Adverse Drug Reaction Reports by Patients
and Healthcare Professionals: A Retrospective Comparative Analysis.
AB - INTRODUCTION: Clinical information is needed to assess the causal relationship
between a drug and an adverse drug reaction (ADR) in a reliable way. Little is
known about the level of relevant clinical information about the ADRs reported by
patients. OBJECTIVE: The aim was to determine to what extent patients report
relevant clinical information about an ADR compared with their healthcare
professional. METHODS: A retrospective analysis of all ADR reports on the same
case, i.e., cases with a report from both the patient and the patient's
healthcare professional, selected from the database of the Dutch
Pharmacovigilance Center Lareb, was conducted. The extent to which relevant
clinical information was reported was assessed by trained pharmacovigilance
assessors, using a structured tool. The following four domains were assessed:
ADR, chronology, suspected drug, and patient characteristics. For each domain,
the proportion of reported information in relation to information deemed relevant
was calculated. An average score of all relevant domains was determined and
categorized as poorly (<=45%), moderately (from 46 to 74%) or well (>=75%)
reported. Data were analyzed using a paired sample t test and Wilcoxon signed
rank test. RESULTS: A total of 197 cases were included. In 107 cases (54.3%),
patients and healthcare professionals reported a similar level of clinical
information. Statistical analysis demonstrated no overall differences between the
groups (p = 0.126). CONCLUSIONS: In a unique study of cases of ADRs reported by
patients and healthcare professionals, we found that patients report clinical
information at a similar level as their healthcare professional. For an optimal
pharmacovigilance, both healthcare professionals and patient should be encouraged
to report.
PMID- 28405900
TI - Evaluation of pre-surgical models for uterine surgery by use of three-dimensional
printing and mold casting.
AB - We propose an approach to supporting pre-surgical planning for the uterus by
integrating medical image analysis and physical model generation based on 3D
printing. With our method, we first segment the patient-specific anatomy and
lesions of the uterus on MR images; then, we create a 3D physical model, an exact
replica of the patient's uterus in terms of size and softness, with transparency
for easy observation of the internal structures of the uterus. In our
experiments, we created pre-surgical models of hysterectomy for five patients who
had been diagnosed to have uterine endometrial cancer. An experienced
radiologist, the surgeons, and all of the patients cooperated in our experiment
for carrying out subjective evaluations of the usefulness of our model. The
accuracy of the physical models was evaluated quantitatively by comparison
between the MR images of the patients and the CT images of the models. The
results showed that the mean values of the errors in gap ranged from 1.19 to 2.22
mm, which was satisfactory for the surgeons. The feedback from both surgeons and
patients demonstrated the usefulness and convenience of the models for efficient
patient explanation understanding and pre-surgical planning by surgeons.
PMID- 28405901
TI - Sexual abuse of minors within the Catholic Church and other institutions : A
literature review.
AB - Sexual violence against children remains a global public health problem. The
health sector has an opportunity and responsibility to be part of the multisector
collaboration to prevent and respond to sexual abuse of minors. The following
article presents a critical analysis of hitherto published empirical studies that
examine the extent and variety of sexual abuse of minors within the Catholic
Church and other institutions. The analysis consists of 40 studies concerning the
Catholic Church and 13 studies concerning other institutions not belonging to the
Catholic Church. We report the characteristics of the offenders and the offenses.
Furthermore, the devastating consequences for children abused by members of
powerful institutions are discussed. Knowledge on the role of institutions in
sexual abuse of minors and psychological distress following these experiences is
necessary to point the way to improvements in prevention and intervention
strategies. This literature review is part of a larger research project on the
sexual abuse of minors in the context of the Catholic Church in Germany (MHG
Study) that is conducted by an interdisciplinary team of psychologists,
psychiatrists, criminologists, and sociologists and is funded by the German
Bishops' Conference.
PMID- 28405902
TI - Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal
Sclerosis.
AB - This study aimed to determine if there is an association between mitophagy and
refractory temporal lobe epilepsy (rTLE) with hippocampal sclerosis. During
epilepsy surgery, we collected tissue samples from the hippocampi and temporal
lobe cortexes of rTLE patients with hippocampal sclerosis (as diagnosed by a
pathologist). Transmission electron microscopy (TEM) was used to study the
ultrastructural features of the tissue. To probe for mitophagy, we used
fluorescent immunolabeling to determine if mitochondrial and autophagosomal
markers colocalized. Fourteen samples were examined. TEM results showed that
early autophagosomes were present and mitochondria were impaired to different
degrees in hippocampi. Immunofluorescent labeling showed colocalization of the
autophagosome marker LC3B with the mitochondrial marker TOMM20 in hippocampi and
temporal lobe cortexes, indicating the presence of mitophagy. Mitochondrial and
autophagosomal marker colocalization was lower in hippocampus than in temporal
lobe cortex (P < 0.001). Accumulation of autophagosomes and mitophagy activation
are implicated in rTLE with hippocampal sclerosis. Aberrant accumulation of
damaged mitochondria, especially in the hippocampus, can be attributed to defects
in mitophagy, which may participate in epileptogenesis.
PMID- 28405903
TI - Stress-Induced Alterations of Immune Profile in Animals Suffering by Tau Protein
Driven Neurodegeneration.
AB - Alzheimer's disease (AD) is a multifactorial disorder; neurofibrillary pathology
composed of tau protein is found side by side with amyloid-beta deposits and
extensive neuroinflammation. The immune system of the brain is considered as one
of the factors that could influence the speed of the progression of AD
neuropathology as a potential mediator of the damage induced by AD protein
deposits. Alzheimer's disease pathology can be impacted by psychological stress;
however, signalling pathways in background are not well known. We have explored
possible avenues of how stress could influence the brain's immune system in a rat
model of AD. Animals were subjected either to a single or multiple instances of
immobilization stress. The analysis of a panel of immunity-related genes was used
to evaluate the impact of stress on the immune response in the brain. We have
identified 19 stress-responsive genes that are involved in neuroinflammation
accompanying tau pathology: Nos2, Ptgs2, IL-8rb, C5, Mmp9, Cx3cr1, CD40lg, Adrb2,
IL-6, IL-6r, IL-1r2, Ccl2, Ccl3, Ccl4, Ccl12, TNF-alpha, IL-1alpha, IL-1beta, IL
10. Most of them are deregulated under the stress conditions also in control
animals; however, the magnitude of the response to either acute or chronic stress
differs. This can lead to serious influence, most probably to acceleration of
neurodegenerative phenotype in diseased animals. Several of the genes (IL-1beta,
Casp1, Cx3cr1 and C5) are deregulated solely in tauopathic animals. The stress
induced changes in the inflammatory picture of the brain highlight the fact that
the brain's immune response is highly responsive to environmental stimuli. The
pattern of changes is indicative of an attempt to protect the brain in the short
term, while being potentially detrimental to the response against a long-term
pathological process such as neurofibrillary degeneration.
PMID- 28405905
TI - Implementation strategies to promote community-engaged efforts to counter tobacco
marketing at the point of sale.
AB - The US tobacco industry spends $8.2 billion annually on marketing at the point of
sale (POS), a practice known to increase tobacco use. Evidence-based policy
interventions (EBPIs) are available to reduce exposure to POS marketing, and
nationwide, states are funding community-based tobacco control partnerships to
promote local enactment of these EBPIs. Little is known, however, about what
implementation strategies best support community partnerships' success enacting
EBPI. Guided by Kingdon's theory of policy change, Counter Tools provides tools,
training, and other implementation strategies to support community partnerships'
performance of five core policy change processes: document local problem,
formulate policy solutions, engage partners, raise awareness of problems and
solutions, and persuade decision makers to enact new policy. We assessed Counter
Tools' impact at 1 year on (1) partnership coordinators' self-efficacy, (2)
partnerships' performance of core policy change processes, (3) community progress
toward EBPI enactment, and (4) salient contextual factors. Counter Tools provided
implementation strategies to 30 partnerships. Data on self-efficacy were
collected using a pre-post survey. Structured interviews assessed performance of
core policy change processes. Data also were collected on progress toward EBPI
enactment and contextual factors. Analysis included descriptive and bivariate
statistics and content analysis. Following 1-year exposure to implementation
strategies, coordinators' self-efficacy increased significantly. Partnerships
completed the greatest proportion of activities within the "engage partners" and
"document local problem" core processes. Communities made only limited progress
toward policy enactment. Findings can inform delivery of implementation
strategies and tests of their effects on community-level efforts to enact EBPIs.
PMID- 28405904
TI - Endocrine Tumors Causing Arterial Hypertension: Pathophysiological Mechanisms and
Clinical Implications.
AB - Some tumors are a relatively rare and amendable cause of hypertension, often
associated with a higher cardiovascular morbidity and mortality, as compared with
that of both general population and patients with essential hypertension. This
worse prognosis is not entirely related to blood pressure increase, because the
release of substances from the tumor can directly influence blood pressure
behavior. Diagnostic approach is challenging and needs a deep knowledge of the
different neuro-hormonal and genetic mechanisms determining blood pressure
increase. Surgical tumor removal can, but not always, cause blood pressure
normalization, depending on how early was tumor detection, since a long-standing
history of hypertension is often associated with a much weaker effect on blood
pressure. Moreover, target organ damage can be affected by the substances
themselves released by the tumors as well as by tumor removal. In this review we
consider the phenotype and genetic features of patients with tumor-induced
hypertension and focus on their diagnostic work-up.
PMID- 28405906
TI - Cross-linguistic transfer in bilinguals reading in two alphabetic orthographies:
The grain size accommodation hypothesis.
AB - Reading acquisition is one of the most complex and demanding learning processes
faced by children in their first years of schooling. If reading acquisition is
challenging in one language, how is it when reading is acquired simultaneously in
two languages? What is the impact of bilingualism on the development of literacy?
We review behavioral and neuroimaging evidence from alphabetic writing systems
suggesting that early bilingualism modulates reading development. Particularly,
we show that cross-linguistic variations and cross-linguistic transfer affect
bilingual reading strategies as well as their cognitive underpinnings. We stress
the fact that the impact of bilingualism on literacy acquisition depends on the
specific combination of languages learned and does not manifest itself similarly
across bilingual populations. We argue that these differences can be explained by
variations due to orthographic depth in the grain sizes used to perform reading
and reading-related tasks. Overall, we propose novel hypotheses to shed light on
the behavioral and neural variability observed in reading skills among
bilinguals.
PMID- 28405907
TI - Bayesian data analysis for newcomers.
AB - This article explains the foundational concepts of Bayesian data analysis using
virtually no mathematical notation. Bayesian ideas already match your intuitions
from everyday reasoning and from traditional data analysis. Simple examples of
Bayesian data analysis are presented that illustrate how the information
delivered by a Bayesian analysis can be directly interpreted. Bayesian approaches
to null-value assessment are discussed. The article clarifies misconceptions
about Bayesian methods that newcomers might have acquired elsewhere. We discuss
prior distributions and explain how they are not a liability but an important
asset. We discuss the relation of Bayesian data analysis to Bayesian models of
mind, and we briefly discuss what methodological problems Bayesian data analysis
is not meant to solve. After you have read this article, you should have a clear
sense of how Bayesian data analysis works and the sort of information it
delivers, and why that information is so intuitive and useful for drawing
conclusions from data.
PMID- 28405908
TI - How orthographic-specific characteristics shape letter position coding: The case
of Thai script.
AB - A central question for any model of visual word identification is the
representation of the position at which letters are encoded (e.g., calm vs.
clam). In this article, we examine whether the orthographic-specific
characteristics of a writing system-namely, Thai-shape the process of letter
position coding. Thai is an alphabetic script that lacks interword spaces and has
an orthographic order that does not necessarily correspond to the phonological
order for initial vowels. This implies that the initial letter position coding in
Thai needs to be flexible enough that readers can successfully encode the letter
positions of words. To compare letter position coding in Thai to that in English,
we conducted an experiment that paralleled Experiment 3 in Gomez, Ratcliff, and
Perea (Psychological Review, 115, 577-600, 2008), including 23 conditions (single
letter replacements, letter transpositions, letter migrations, and a
corresponding control). We obtained fits from Gomez et al.'s overlap model, which
is a model that has been shown to account for letter position coding in the Roman
alphabet across this variety of letter manipulations. The overlap model was found
to successfully fit the Thai data. Our results revealed that the position
encoding was better for the first letter than for the rest of the positions in
both languages; however, in English the position uncertainty grows as a function
of letter order quite abruptly, whereas in Thai it grows gradually. Thus, the
orthographic-specific characteristics of the Thai writing system do play a role
in shaping the process of letter position coding.
PMID- 28405909
TI - The nature of the association between binge-eating severity and metabolic
syndrome.
PMID- 28405911
TI - A new biopesticide from a local Bacillus thuringiensis var. tenebrionis (Xd3)
against alder leaf beetle (Coleoptera: Chrysomelidae).
AB - Use of chemical pesticides in agriculture harms humans, non-target organisms and
environments, and causes increase resistance against chemicals. In order to
develop an effective bio-pesticide against coleopterans, particularly against
Agelastica alni (Coleoptera: Chrysomelidae) which is one of the serious pests of
alder leaf and hazelnut, we tested the insecticidal effect of 21 Bacillus
isolates against the larvae and adults of the pest. Bacillus thuringiensis var.
tenebrionis-Xd3 (Btt-Xd3) showed the highest insecticidal effect based on
screening tests. For toxin protein production and high sporulation of Xd3, the
most suitable medium, pH and temperature conditions were determined as nutrient
broth medium enriched with salts, pH 7 and 30 degrees C, respectively.
Sporulated Btt-Xd3 in nutrient broth medium enriched with salts transferred to
fermentation medium containing soybean flour, glucose and salts. After
fermentation, the mixture was dried in a spray dryer, and spore count of the
powder product was determined as 1.6 * 1010 c.f.u. g-1. Moisture content,
suspensibility and wettability of the formulation were determined as 8.3, 86% and
21 s, respectively. Lethal concentrations (LC50) of formulated Btt-Xd3 were
determined as 0.15 * 105 c.f.u. ml-1 for larvae at laboratory conditions. LC50
values were also determined as 0.45 * 106 c.f.u. ml-1 at the field condition on
larval stage. Our results showed that a new bio-pesticide developed from B.
thuringiensis tenebrionis (Xd3) (Btt-Xd3) may be valuable as a biological control
agent for coleopteran pests.
PMID- 28405910
TI - Omics analysis of acetic acid tolerance in Saccharomyces cerevisiae.
AB - Acetic acid is an inhibitor in industrial processes such as wine making and
bioethanol production from cellulosic hydrolysate. It causes energy depletion,
inhibition of metabolic enzyme activity, growth arrest and ethanol productivity
losses in Saccharomyces cerevisiae. Therefore, understanding the mechanisms of
the yeast responses to acetic acid stress is essential for improving acetic acid
tolerance and ethanol production. Although 329 genes associated with acetic acid
tolerance have been identified in the Saccharomyces genome and included in the
database (
http://www.yeastgenome.org/observable/resistance_to_acetic_acid/overview ), the
cellular mechanistic responses to acetic acid remain unclear in this organism.
Post-genomic approaches such as transcriptomics, proteomics, metabolomics and
chemogenomics are being applied to yeast and are providing insight into the
mechanisms and interactions of genes, proteins and other components that together
determine complex quantitative phenotypic traits such as acetic acid tolerance.
This review focuses on these omics approaches in the response to acetic acid in
S. cerevisiae. Additionally, several novel strains with improved acetic acid
tolerance have been engineered by modifying key genes, and the application of
these strains and recently acquired knowledge to industrial processes is also
discussed.
PMID- 28405912
TI - Continuous Transdermal Delivery of L-DOPA Based on a Self-Assembling Nanomicellar
System.
AB - PURPOSE: When levodopa (L-DOPA) is administered orally, it is eliminated from the
body very quickly resulting in a series of sharp fluctuations in its blood
concentrations. These frequent changes in blood levels are considered to be
responsible for the development of late motor complications and dyskinesias,
which are troubling clinical and treatment issues in Parkinson's disease.
Transdermal drug delivery is a patient-compliant method for delivering
therapeutics into the systemic circulation in a continuous and controlled manner.
Transdermal delivery of L-DOPA can achieve continuous dopaminergic stimulation
(CDS), thus reducing motor fluctuations. METHODS: However, there are two
technical difficulties in the development of a transdermal patch for L-DOPA: (a)
L-DOPA is poorly soluble in most pharmaceutically-acceptable solvents, and (b) L
DOPA has a limited permeability through the skin even from saturated solutions.
We have, therefore, investigated the transdermal delivery of L-DOPA using an
innovative self-assembling nano-micellar system (SANS), loaded with 2% L-DOPA and
1% carbidopa. RESULTS: In vitro testing as well as in vivo pharmacokinetic
studies (multiple-dose regimen) in rabbits have demonstrated for the first time a
significantly increased percutaneous permeation and systemic absorption of L
DOPA. CONCLUSIONS: It has therefore been proposed that either a once-daily or a
twice-daily regimen could be therapeutically effective depending on the severity
of the disease.
PMID- 28405913
TI - In Vitro Transport Activity and Trafficking of MRP2/ABCC2 Polymorphic Variants.
AB - PURPOSE: Multidrug resistance-associated protein 2 (MRP2/ABCC2) is an efflux pump
that removes drugs and chemicals from cells. We sought to characterize the
expression, trafficking and in vitro activity of seven single nucleotide
polymorphisms (SNPs) in the ABCC2 gene. METHODS: ABCC2 SNPs were generated using
site-directed mutagenesis and stably expressed in Flp-In HEK293 cells, which
allows targeted insertion of transgenes within the genome. Total and cell surface
expression of MRP2 as well as accumulation of substrates (calcein AM and 5(6)
carboxy-2',7'-dichlorofluorescein diacetate, CDCF) were quantified in cells or
inverted membrane vesicles expressing wild-type (WT) or variant forms. RESULTS:
The cell surface expression of the C-24T-, G1249A-, G3542T-, T3563A-, C3972T- and
G4544A-MRP2 variants was similar to WT-MRP2. While expression was similar,
transport of calcein AM was enhanced in cells expressing the G3542T-, T3563A-,
C3972T-, and G4544A-MRP2 variants. By comparison, cells expressing the C2366T
MRP2 variant had 40-50% lower surface expression, which increased the
accumulation of calcein AM up to 3-fold. Accumulation of CDCF in inverted
membrane vesicles expressing the C2366T-MRP2 variant was also reduced by 50%. In
addition, the G1249A-MRP2 variant had decreased transport of CDCF. CONCLUSIONS:
Taken together, these data demonstrate that genetic variability in the ABCC2 gene
influences the in vitro expression, trafficking, and transport activity of MRP2.
PMID- 28405914
TI - Cyclosporine A Loaded Electrospun Poly(D,L-Lactic Acid)/Poly(Ethylene Glycol)
Nanofibers: Drug Carriers Utilizable in Local Immunosuppression.
AB - PURPOSE: The present study aims to prepare poly(D,L-lactic acid) (PLA) nanofibers
loaded by the immunosuppressant cyclosporine A (CsA, 10 wt%). Amphiphilic
poly(ethylene glycol)s (PEG) additives were used to modify the hydrophobic drug
release kinetics. METHODS: Four types of CsA-loaded PLA nanofibrous carriers
varying in the presence and molecular weight (MW) of PEG (6, 20 and 35 kDa) were
prepared by needleless electrospinning. The samples were extracted for 144 h in
phosphate buffer saline or tissue culture medium. A newly developed and validated
LC-MS/MS method was utilized to quantify the amount of released CsA from the
carriers. In vitro cell experiments were used to evaluate biological activity.
RESULTS: Nanofibers containing 15 wt% of PEG showed improved drug release
characteristics; significantly higher release rates were achieved in initial part
of experiment (24 h). The highest released doses of CsA were obtained from the
nanofibers with PEG of the lowest MW (6 kDa). In vitro experiments on ConA
stimulated spleen cells revealed the biological activity of the released CsA for
the whole study period of 144 h and nanofibers containing PEG with the lowest MW
exhibited the highest impact (inhibition). CONCLUSIONS: The addition of PEG of a
particular MW enables to control CsA release from PLA nanofibrous carriers. The
biological activity of CsA-loaded PLA nanofibers with PEG persists even after 144
h of previous extraction. Prepared materials are promising for local
immunosuppression in various medical applications.
PMID- 28405915
TI - Does Aphid Infestation Interfere with Indirect Plant Defense against Lepidopteran
Caterpillars in Wild Cabbage?
AB - Attraction of parasitoids to plant volatiles induced by multiple herbivory
depends on the specific combinations of attacking herbivore species, especially
when their feeding modes activate different defense signalling pathways as has
been reported for phloem feeding aphids and tissue feeding caterpillars. We
studied the effects of pre-infestation with non-host aphids (Brevicoryne
brassicae) for two different time periods on the ability of two parasitoid
species to discriminate between volatiles emitted by plants infested by host
caterpillars alone and those emitted by plants infested with host caterpillars
plus aphids. Using plants originating from three chemically distinct wild cabbage
(Brassica oleracea) populations, Diadegma semiclausum switched preference for
dually infested plants to preference for plants infested with Plutella xylostella
hosts alone when the duration of pre-aphid infestation doubled from 7 to 14 days.
Microplitis mediator, a parasitoid of Mamestra brassicae caterpillars, preferred
dually-infested plants irrespective of aphid-infestation duration. Separation of
the volatile blends emitted by plants infested with hosts plus aphids or with
hosts only was poor, based on multivariate statistics. However, emission rates of
individual compounds were often reduced in plants infested with aphids plus hosts
compared to those emitted by plants infested with hosts alone. This effect
depended on host caterpillar species and plant population and was little affected
by aphid infestation duration. Thus, the interactive effect of aphids and hosts
on plant volatile production and parasitoid attraction can be dynamic and
parasitoid specific. The characteristics of the multi-component volatile blends
that determine parasitoid attraction are too complex to be deduced from simple
correlative statistical analyses.
PMID- 28405916
TI - Influences of Media Compositions on Characteristics of Isolated Bacteria
Exhibiting Lignocellulolytic Activities from Various Environmental Sites.
AB - Efficient isolation of lignocellulolytic bacteria is essential for the
utilization of lignocellulosic biomass. In this study, bacteria with
cellulolytic, xylanolytic, and lignolytic activities were isolated from
environmental sites such as mountain, wetland, and mudflat using isolation media
containing the combination of lignocellulose components (cellulose, xylan, and
lignin). Eighty-nine isolates from the isolation media were characterized by
analyzing taxonomic ranks and cellulolytic, xylanolytic, and lignolytic
activities. Most of the cellulolytic bacteria showed multienzymatic activities
including xylanolytic activity. The isolation media without lignin were efficient
in isolating bacteria exhibiting multienzymatic activities even including
lignolytic activity, whereas a lignin-containing medium was effective to isolate
bacteria exhibiting lignolytic activity only. Multienzymatic activities were
mainly observed in Bacillus and Streptomyces, while Burkholderia was the most
abundant genus with lignolytic activity only. This study provides insight into
isolation medium for efficient isolation of lignocellulose-degrading
microorganisms.
PMID- 28405917
TI - Key Intervention Characteristics in e-Health: Steps Towards Standardized
Communication.
AB - PURPOSE: This paper reports expert opinion on e-health intervention
characteristics that enable effective communication of characteristics across the
diverse field of e-health interventions. The paper presents a visualization tool
to support communication of the defining characteristics. METHODS: An initial
list of e-health intervention characteristics was developed through an iterative
process of item generation and discussion among the 12 authors. The list was
distributed to 123 experts in the field, who were emailed an invitation to assess
and rank the items. Participants were asked to evaluate these characteristics in
three separate ways. RESULTS: A total of 50 responses were received for a
response rate of 40.7%. Six respondents who reported having little or no
expertise in e-health research were removed from the dataset. Our results suggest
that 10 specific intervention characteristics were consistently supported as of
central importance by the panel of 44 e-intervention experts. The weight and
perceived relevance of individual items differed between experts; oftentimes,
this difference is a result of the individual theoretical perspective and/or
behavioral target of interest. CONCLUSIONS: The first iteration of the
visualization of salient characteristics represents an ambitious effort to
develop a tool that will support communication of the defining characteristics
for e-health interventions aimed to assist e-health developers and researchers to
communicate the key characteristics of their interventions in a standardized
manner that facilitates dialog.
PMID- 28405918
TI - Hepcidin suppression in beta-thalassemia is associated with the down-regulation
of atonal homolog 8.
AB - Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin
transcription, which links erythropoietic activity with iron-sensing molecules.
In the present study, we investigated the association between hepcidin and ATOH8
expression in beta-thalassemia. We found that inhibition of hepcidin expression
in beta-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin
1 (Hamp1) and Atoh8 mRNA expression were down-regulated in beta-thalassemic mice.
Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7
cells cultured in medium supplemented with beta-thalassemia patient serum. The
Huh7 cells, which were transfected with ATOH8-FLAG expression plasmid and
cultured in the supplemented medium, exhibited increased levels of ATOH8 mRNA,
ATOH8-FLAG protein, pSMAD1,5,8, and HAMP mRNA. Interestingly, over-expression of
ATOH8 reversed the effects of hepcidin suppression induced by the beta
thalassemia patient sera. In conclusion, hepcidin suppression in beta-thalassemia
is associated with the down-regulation of ATOH8 in response to anemia. We,
therefore, suggest that ATOH8 is an important transcriptional regulator of
hepcidin in beta-thalassemia.
PMID- 28405919
TI - Iron overload may promote alteration of NK cells and hematopoietic
stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.
AB - The objective of the study was to examine levels of intracellular iron, reactive
oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and
hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore
potential mechanisms by which iron overload (IOL) promotes MDS progression.
Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were
included. HSPCs and NK cells were isolated by magnetic absorption cell sorting.
We used flow cytometry to detect the levels of ROS and intracellular JNK and P38
in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and
CD34+ cells to examine the expression of JNK and p38MAPK using RT-PCR and Western
blotting. Intracellular iron concentration was detected. Data were analyzed by
SPSS 21 statistical software. Intracellular iron concentration and ROS were
increased in both NK cells and HSPCs in MDS patients with iron overload (P <
0.05). MDS patients with iron overload had higher JNK expression and lower p38
expression in NK cells, and higher p38 expression in HSPCs compared with non-iron
overload group. IOL may cause alterations in NK cells and HSPCs through the JNK
and p38 pathways, and play a role in the transformation to AML from MDS.
PMID- 28405920
TI - Effector functions of memory CTLs can be affected by signals received during
reactivation.
AB - Memory cytotoxic T lymphocytes (CTLs) are able to provide protections to the host
against repeated insults from intracellular pathogens. However, it has not been
completely understood how the effector functions of memory CTLs are induced upon
antigen challenge, which is directly related to the efficacy of their protection.
Third signal cytokines, such as IL-12 and type I interferon, have been suggested
to be involved in the protective function of memory CTLs, but direct evidence is
warranted. In this report, we found that memory CTLs need to be reactivated to
exert effector functions. Infusion of a large population of quiescent memory CTLs
did not lead to cancer control in tumor-bearing mice, whereas infusion of a
reactivated memory CTL population did. This reactivation of memory CTLs requires
cytokines such as IL-12 in addition to antigen but was less dependent upon
costimulation and IL-2 compared to naive CTLs. Memory CTLs responded more quickly
and with greater strength than their naive counterparts upon stimulation, which
is associated with higher upregulation of important transcription factors such as
T-bet and phosphorylated STAT4. In addition, memory CTLs underwent less expansion
than naive CTLs upon pathogen challenge. In conclusion, effector functions of
established memory CTLs may be affected by certain cytokines such as IL-12 and
type I IFN. Thus, a pathogen's ability to induce cytokines could contribute to
the efficacy of protection of an established memory CTL population.
PMID- 28405921
TI - The Role of Early Molecular Response in the Management of Chronic Phase CML.
AB - PURPOSE OF REVIEW: Although tyrosine kinase inhibitors (TKIs) spectacularly
improve the disease burden and the overall survival of chronic myeloid leukemia
patients, early identification of a subset of poor TKI responders has been
recognized as a critical goal to prevent disease progression in these patients.
We herein review the past and recent evidence on the impact of early response.
RECENT FINDINGS: In the recent years, the achievement of an early molecular
response (EMR, defined as 3-month BCR-ABL1 transcript <10% IS) has emerged as a
useful tool to identify poor-risk patients. Although several groups have reported
the importance of such milestone, clinical intervention based on it remains
controversial partly due to its low specificity to predict progression, which may
be partially improved by using the rate of decline in BCR-ABL1 transcript level
(halving time or velocity of ratio reduction). Standardization of halving time or
velocity of ratio reduction will likely help establishing more stringent
recommendation and modify current clinical practices.
PMID- 28405922
TI - New semi-pilot-scale reactor to study the photocatalytic inactivation of phages
contained in aerosol.
AB - The aims of this work were to design and build a photocatalytic reactor (UV
A/TiO2) to study the inactivation of phages contained in bioaerosols, which
constitute the main dissemination via phages in industrial environments. The
reactor is a close system with recirculation that consists of a stainless steel
camera (cubic form, side of 60 cm) in which air containing the phage particles
circulates and an acrylic compartment with six borosilicate plates covered with
TiO2. The reactor is externally illuminated by 20 UV-A lamps. Both compartments
are connected by a fan to facilitate the sample circulation. Samples are injected
into the camera using two piston nebulizers working in series whereas several
methodologies for sampling (impinger/syringe, sampling on photocatalytic plates,
and impact of air on slide) were assayed. The reactor setup was carried out using
phage B1 (Lactobacillus plantarum), and assays demonstrated a decrease of phage
counts of 2.7 log orders after 1 h of photocatalytic treatment. Photonic
efficiencies of inactivation were assessed by phage sampling on the
photocatalytic plates or by impact of air on a glass slide at the photocatalytic
reactor exit. Efficiencies of the same order of magnitude were observed using
both sampling methods. This study demonstrated that the designed photocatalytic
reactor is effective to inactivate phage B1 (Lb. plantarum) contained in
bioaerosols.
PMID- 28405923
TI - In situ measurement with diffusive gradients in thin films: effect of biofouling
in freshwater.
AB - Concerning in situ passive sampler deployment, several technical priorities must
be considered. In particular, deployment time must be sufficiently long not only
to allow a significant quantity to be accumulated to facilitate analysis but also
to ensure that the signal is above the quantification limit and out of the blank
influence. Moreover, regarding the diffusive gradient in thin films (DGT)
technique, deployment time must also be sufficiently long (at least 5 days) to
avoid the interactions of the solutes with the material diffusion layer of the
DGT and for the steady state to be reached in the gel. However, biofouling occurs
in situ and modifies the surface of the samplers. In this article, we propose a
kinetic model which highlights the biofouling effect. This model was able to
describe the mitigation of the flux towards the DGT resin observed on Cd, Co, Mn,
Ni and Zn during a 22-day deployment in the Seine River. Over a period of 22
days, biofouling had a significant impact on the DGT concentrations measured,
which were decreased twofold to threefold when compared to concentrations
measured in unaffected DGTs.
PMID- 28405924
TI - The photocatalytic degradation of carbofuran and Furadan 35-ST: the influence of
inert ingredients.
AB - A comparative study on photocatalytic degradation of the pesticide carbofuran and
its commercial product Furadan 35-ST in an aqueous suspension of ZnO, irradiated
by long-wave light (315-400 nm), is presented in this study. In order to assess
the effects of inert ingredients present in the commercial product Furadan 35-ST,
non-competitive and competitive adsorption and kinetic studies of carbofuran
degradation processes were conducted. A higher photochemical degradation rate was
found for pure carbofuran in comparison to a two-component system, carbofuran and
single addition of ingredients at appropriate concentrations, and the commercial
product Furadan 35-ST. The overall effect of inert ingredients was evaluated from
a competitive study using the model system of Furadan 35-ST. The results of a
mineralization study, obtained by ion chromatography (IC) and total organic
carbon (TOC) analyses, revealed the formation of acetate, oxalate, and formate
ions. Photodegradation products of carbofuran, three of them detected for the
first time, were identified based on high-performance liquid chromatography
tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-mass spectrometry
(GC-MS) results, and their photodegradation pathways were proposed.
PMID- 28405925
TI - A survey of metal concentrations in marine sediment cores in the vicinity of an
old mercury-mining area in Karaburun, Aegean Sea.
AB - The aim of this study was to assess the historical trends of metal concentrations
in coastal sediments in the vicinity of an inactive mining area, find background
values and contamination levels of metals around the Karaburun peninsula, and
then search for other sources of mercury in marine sediment cores using
multivariate statistical analysis and report the potential ecological risks from
that metal contamination. Surface sediment samples were taken from seven
stations. Water depths were less than 20 m (coastal area) at stations KB07 and
KB08. The depths at stations KB01, KB02, and KB03 were between 20 and 40 m, and
stations KB05 and KB06 were more than 40 m (open area). In surface sediments at
depths between 20 and 40 m, Mo, Cu, Pb, Zn, Ni, Co, Fe, Cd, Ti, Zr, Sn, As, Y,
and Hg levels revealed higher contamination factors (Cf) compared to those of the
coastal and open areas. Also, sediment samples were taken for historical records
at stations KB01 and KB02 for 2012. Metal concentrations of Cu, Zn, Ni, Co, As,
Sb, Cr, Ba, Ti, Al, and Hg in the sediment core samples were significantly higher
during the Holocene (~5700 BC to 2000 B.C.) and Medieval Warm periods (~1000 A.D.
to 1400 A.D.) and tended to decrease towards the Little Ice Age (2200 B.C. to the
birth of Jesus Christ). Background concentration of Hg in sediment was found as
1.67 MUg/g around the Karaburun peninsula. Average EF values higher than 20 were
identified for As, Hg, Sb, and Ca. Ni and Hg levels were found above the PEL
values. It was determined that the accumulation effect of Hg coming from the
mafic rocks due to erosion in the marine environment was higher than that of Hg
coming from the mine. The factor analyses showed an association between Hg, Ni,
and Co. This reveals the importance of the contribution of mafic rocks reaching
the marine environment by wave erosion. According to the factor analyses, high
concentrations of Pb, Zn, Cd, As, Sb, Ba, Ti, and Zr were detected in the
lithogenic sources.
PMID- 28405926
TI - The use of theatre in medical education in the emergency cases school: an
appealing and widely accessible way of learning.
AB - INTRODUCTION: Theatre models in medical education have been used worldwide in
order to train medical students and graduates in managing various situations.
However, the literature reports little regarding its appeal to trainees. We
conducted a medical seminar, entitled Emergency Cases School, which employed such
techniques. Actors simulated the actions of doctors and patients involved in
various emergency cases, in front of a large audience, in a specially modified
theatre hall which resembled the emergency room environment. METHODS: A total of
303 undergraduate medical students participated in the seminar. The audience
evaluated the course with the DREEM questionnaire, along with two extra
questions: Q1. 'Do you think that the course will prove itself beneficial to your
clinical skills?' and Q2. 'Would you suggest the course to another student?', in
a 0-4 scoring scale. Of the attendees, 281 (92.7%) answered the questionnaire.
RESULTS: The overall DREEM score was 140.32 (+/-23.39) out of 150, which is
interpreted as 'More positive than negative'. The results of Q1 and Q2 were 3.07
(+/-0.78) and 3.65 (+/-0.61), respectively. DISCUSSION: The Emergency Cases
School received positive feedback as a theatre educational tool, targeted to a
large audience. With the advantage of the realistic setting of an emergency room,
along with its low-budget needs, this course model could function as a creative
alternative of the more traditional lecturing teaching techniques.
PMID- 28405927
TI - Characterization of indeterminate renal masses with molecular imaging: how do we
turn potential into reality?
PMID- 28405928
TI - Adynamic bone disease is a predominant bone pattern in early stages of chronic
kidney disease.
AB - Chronic kidney disease (CKD) is complicated by disturbances of mineral and bone
metabolism which start early in the course of the disease. It has long been
assumed that high turnover bone lesions induced by secondary hyperparathyroidism
are the predominant type of renal osteodystrophy from the start. However, there
is increasing evidence in favor of the view that in early CKD stages low bone
turnover is prevailing, with adynamic bone disease being the predominant form.
Since serum parathyroid hormone levels increase progressively early on, and the
most probable explanation is resistance to the skeletal action of this hormone.
An early inhibition of the Wnt pathway with an increase in sclerostin and other
inhibitors of Wnt signaling may be involved. Finally, a variety of other uremic
toxins such as indoxyl sulfate and phosphate may play an important role in the
pathogenesis of the low turnover bone disease observed in early stages of CKD.
The optimal strategies to prevent and to treat adynamic bone disease in incipient
CKD yet need to be defined. Targeting uremic toxins such as sclerostin,
phosphate, and indoxyl sulfate may be relevant.
PMID- 28405931
TI - National Institutes of Health Blueprint Neurotherapeutics Network: Results to
Date and Path Forward.
PMID- 28405930
TI - Single-cell sequencing and tumorigenesis: improved understanding of tumor
evolution and metastasis.
AB - Extensive genomic and transcriptomic heterogeneity in human cancer often
negatively impacts treatment efficacy and survival, thus posing a significant
ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA
sequencing methods now provide high-resolution genomic and gene expression
portraits of individual cells, facilitating the study of complex molecular
heterogeneity in cancer. Important developments in single-cell sequencing (SCS)
technologies over the past 5 years provide numerous advantages over traditional
sequencing methods for understanding the complexity of carcinogenesis, but
significant hurdles must be overcome before SCS can be clinically useful. In this
review, we: (1) highlight current methodologies and recent technological advances
for isolating single cells, single-cell whole-genome and whole-transcriptome
amplification using minute amounts of nucleic acids, and SCS, (2) summarize
research investigating molecular heterogeneity at the genomic and transcriptomic
levels and how this heterogeneity affects clonal evolution and metastasis, and
(3) discuss the promise for integrating SCS in the clinical care arena for
improved patient care.
PMID- 28405932
TI - Synthesis, Characterization and Solvatochromic Studies Using the Solvent Polarity
Parameter, ENT on 2-Chloro-3-Ethylamino-1,4-Naphthoquinone.
AB - Quinones are molecules with varied biological activities and electronic
properties which are used for important applications [1, 2]. Quinone with a
heteroatom substituted, namely 2-chloro-3-ethylamino-1,4-naphthoquinone (N-CAN)
was synthesized and characterized by various techniques such as H1-NMR, C13-NMR,
Mass spectroscopy and FT-IR spectroscopy. In this study, the solvatochromic
effects on the spectral properties of 2-chloro-3-ethylamino-1,4-naphthoquinone
have been investigated in different solvents taking into consideration, the
solvent parameters like dielectric constant (epsilon) and refractive index (eta)
of different solvent polarities. Using Lippert-Mataga, Bakshiev's, Kawski-Chamma
Viallet and Reichardt equations, the ground state (MUg) and excited state (MUe)
dipole moments were calculated. The angle between the excited state and ground
state dipole moments were also calculated. Graphical Abstract ?.
PMID- 28405929
TI - Thermodynamics in cancers: opposing interactions between PPAR gamma and the
canonical WNT/beta-catenin pathway.
AB - Cancer cells are the site of numerous metabolic and thermodynamic abnormalities.
We focus this review on the interactions between the canonical WNT/beta-catenin
pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in
cancers and their implications from an energetic and metabolic point of view. In
numerous tissues, PPAR gamma activation induces inhibition of beta-catenin
pathway, while the activation of the canonical WNT/beta-catenin pathway
inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated
while the WNT/beta-catenin pathway is upregulated. In cancer cells, upregulation
of the WNT/beta-catenin signaling induces dramatic changes in key metabolic
enzymes that modify their thermodynamic behavior. This leads to activation of
pyruvate dehydrogenase kinase1 (PDK-1) and monocarboxylate lactate transporter.
Consequently, phosphorylation of PDK-1 inhibits the pyruvate dehydrogenase
complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl
coenzyme A (acetyl-CoA) in mitochondria and only a part of acetyl-CoA can enter
the tricarboxylic acid cycle. This leads to aerobic glycolysis in spite of the
availability of oxygen. This phenomenon is referred to as the Warburg effect.
Cytoplasmic pyruvate is converted into lactate. The WNT/beta-catenin pathway
induces the transcription of genes involved in cell proliferation, i.e., MYC and
CYCLIN D1. This ultimately promotes the nucleotide, protein and lipid synthesis
necessary for cell growth and multiplication. In cancer, activation of the PI3K
AKT pathway induces an increase of the aerobic glycolysis. Moreover,
prostaglandin E2 by activating the canonical WNT pathway plays also a role in
cancer. In addition in many cancer cells, PPAR gamma is downregulated. Moreover,
PPAR gamma contributes to regulate some key circadian genes. In cancers,
abnormalities in the regulation of circadian rhythms (CRs) are observed. CRs are
dissipative structures which play a key-role in far-from-equilibrium
thermodynamics. In cancers, metabolism, thermodynamics and CRs are intimately
interrelated.
PMID- 28405933
TI - Detection of p53 Gene Mutation (Single-Base Mismatch) Using a Fluorescent Silver
Nanoclusters.
AB - P53 mutation was detected through the application of a biosensing approach based
on the decrease in the fluorescence of oligonucleotide-templated silver
nanoclusters (DNA-AgNCs). To this end specific DNA scaffolds of two various
nucleotide fragments were used. One of the scaffolds was enriched with two
cytosine sequence fragment (C12). This led to DNA-AgNCs with a fluorescence
intensity through chemical reduction, while the other scaffold acted as the probe
fragment (5- GTAGATGGCCATGGCGCGGACGCGGGTG-3). This latter scaffold selectively
bound to the specific p53 site. Thus, resulting AgNCs demonstrated decreased
fluorescence upon binding to single-base mismatching targets, and this behavior
was found to be linearly proportional to the concentration of mutated p53 from 5
to 350 nM and the approach was found to be able to detect concentrations as low
as 1.3 nM.
PMID- 28405934
TI - A Brief Review of Neurotoxicity Induced by Melamine.
AB - In September 2008, in China, tens of thousands of children were hospitalized,
several even died, as a result of infant-formula milk adulterated with a
synthetic chemical compound, melamine, and in the next few months, this crisis
became the focus of attention worldwide. Although there are a number of articles
about nephrotoxicity of melamine, the evidence of melamine toxicity on other
organs is still scanty. Specially, several recent studies indicated that melamine
can perturb the central nervous system (CNS) function and induce cognitive
deficits, breaking the previous view that melamine toxicity is limited to the
urinary system. This review focuses on some developmental consequences of
melamine exposures through various routes in vitro and in vivo, from ethology to
molecular and cellular assessments. The evidences demonstrate that the neurotoxic
effects of melamine were varied from different route exposure. Finally, the
relevant literature on the mechanisms of these aspects has been discussed, and
some suggestions towards further researches have been presented.
PMID- 28405935
TI - 4'-Chlorodiazepam Protects Mitochondria in T98G Astrocyte Cell Line from Glucose
Deprivation.
AB - The translocator protein (TSPO), formerly known as the peripheral-type
benzodiazepine receptor (PBR), is considered an important regulator of
steroidogenesis and a potential therapeutic target in neurological disorders.
Previous evidence suggests that TSPO ligands can protect cells during injury and
prevent apoptosis in central nervous system (CNS) cells. However, its actions on
astrocytic cells under metabolic injury are not well understood. In this study,
we explored whether 4'-chlorodiazepam (Ro5-4864), a TSPO ligand, might protect
astrocyte mitochondria under glucose deprivation. Our results showed that 4'
chlorodiazepam preserved cell viability and reduced nuclear fragmentation in
glucose-deprived cells. These effects were accompanied by a reduced production of
free radicals and maintenance of mitochondrial functions in cells treated with 4'
chlorodiazepam. Finally, our findings suggest that TSPO might be involved in
reducing oxidative stress by preserving mitochondrial functions in astrocytic
cells exposed to glucose withdrawal.
PMID- 28405936
TI - Population Pharmacokinetics: Some Observations in Pediatric Modeling for Drug
Clearance.
AB - The objective of this study is to evaluate the predictive performance of several
models to predict drug clearance in preterm and term neonates. Five models using
different types of allometric and linear models were developed. Two sets of data
were used to develop these models (data from preterm neonates to adults and data
from preterm and term neonates). Models were also developed with (normalized to
70 kg) or without body weight normalization (body weight 1 kg). From the
literature, clearance values for four drugs from neonates to adults were
obtained. External data were used to evaluate the predictive performance of these
models in preterm and term neonates. The results of the study indicated that (1)
normalization to a standard body weight had no impact on the predictive
performance of the models, (2) the model developed from preterm neonates to
adults using fixed exponent 0.75 provided inaccurate estimate (overestimation) of
drug clearance in neonates, (3) a far superior prediction of clearance was
observed with the model when the exponents of allometry were estimated than the
model using exponent 0.75, (4) linear models with the exception of the model with
intercept provided comparable results to the estimated exponent model and were
superior in their predictive performance to the model using exponent 0.75, and
(5) when the models were developed from neonate data, the predictive performance
of all models were similar. Overall, the study indicated that body weight
normalization had no impact on the performance of model prediction, the exponents
of allometry in pharmacostatistical models should be estimated rather than fixed,
and more studies are needed to evaluate the suitability of linear models for the
prediction of drug clearance in neonates.
PMID- 28405937
TI - New Cardiac Imaging Algorithms to Diagnose Constrictive Pericarditis Versus
Restrictive Cardiomyopathy.
AB - PURPOSE OF REVIEW: Echocardiography is the mainstay in the diagnostic evaluation
of constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM), but no
single echocardiographic parameter is sufficiently robust to accurately
distinguish between the two conditions. The present review summarizes the recent
advances in echocardiography that promise to improve its diagnostic performance
for this purpose. The role of other imaging modalities such as cardiac computed
tomography, magnetic resonance imaging, and invasive hemodynamic assessment in
the overall diagnostic approach is also discussed briefly. RECENT FINDINGS: A
recent study has demonstrated improved diagnostic accuracy of echocardiography
with integration of multiple conventional echocardiographic parameters in to a
step-wise algorithm. Concurrently, the studies using speckle-tracking
echocardiography have revealed distinct and disparate patterns of myocardial
mechanical abnormalities in CP and RCM with their ability to distinguish between
the two conditions. The incorporation of machine-learning algorithms into
echocardiography workflow permits easy integration of the wealth of the
diagnostic data available and promises to further enhance the diagnostic accuracy
of echocardiography. New imaging algorithms are continuously being evolved to
permit accurate distinction between CP and RCM. Further research is needed to
validate the accuracy of these newer algorithms and to define their place in the
overall diagnostic approach for this purpose.
PMID- 28405939
TI - Simple and Environmentally Friendly Fabrication of Superhydrophobic Alkyl Ketene
Dimer Coated MALDI Concentration Plates.
AB - Here we present a method to manufacture peptide-concentrating MALDI-plates with
alkyl ketene dimer (AKD) as a new superhydrophobic coating. The fabrication of
the hydrophobic plates included application of AKD by airbrush, and negative
contact printing to generate the concentration sites. Deposited sample droplets
were contained within the prestructured sites, and self-adjusted onto the site if
slightly misplaced. No AKD contamination was observed, and the plates could
easily be cleaned and regenerated. The S/N values for four model peptides was
about twice as high compared with a standard steel plate and a commercial
concentration plate. Graphical Abstract ?.
PMID- 28405938
TI - Genetic Architecture of Familial Hypercholesterolaemia.
AB - PURPOSE OF REVIEW: Familial hypercholesterolaemia (FH) is an inherited disorder
of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised
cholesterol level from birth and a high risk of premature coronary heart disease.
In this paper, we review the genetic basis of FH and its impact on the clinical
presentation. RECENT FINDINGS: Mutations in any of three genes (LDLR, APOB and
PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in
only ~40% of patients with a clinical diagnosis of FH. In the remainder, a
polygenic aetiology is most likely, due to the co-inheritance of common LDL-C
raising variants. The cardiovascular presentation and management of FH will
differ between patients based on their underlying genetic factors. New genotyping
methods such as next-generation sequencing will provide us with better
understanding of the genetic architecture of FH.
PMID- 28405940
TI - Assessing the Interplay between the Physicochemical Parameters of Ion-Pairing
Reagents and the Analyte Sequence on the Electrospray Desorption Process for
Oligonucleotides.
AB - Alkylamines are widely used as ion-pairing agents during LC-MS of
oligonucleotides. In addition to a better chromatographic separation, they also
assist with the desorption of oligonucleotide ions into the gas phase, cause
charge state reduction, and decrease cation adduction. However, the choice of
such ion-pairing agents has considerable influence on the MS signal intensity of
oligonucleotides as they can also cause significant ion suppression.
Interestingly, optimal ion-pairing agents should be selected on a case by case
basis as their choice is strongly influenced by the sequence of the
oligonucleotide under investigation. Despite imposing major practical
difficulties to analytical method development, such a highly variable system that
responds very strongly to the nuances of the electrospray composition provides an
excellent opportunity for a fundamental study of the electrospray ionization
process. Our investigations using this system quantitatively revealed the major
factors that influenced the ESI ionization efficiency of oligonucleotides.
Parameters such as boiling point, proton affinity, partition coefficient, water
solubility, and Henry's law constants for the ion-pairing reagents and the
hydrophobic thymine content of the oligonucleotides were found to be the most
significant contributors. Identification of these parameters also allowed for the
development of a statistical predictive algorithm that can assist with the choice
of an optimum IP agent for each particular oligonucleotide sequence. We believe
that research in the field of oligonucleotide bioanalysis will significantly
benefit from this algorithm (included in Supplementary Material) as it advocates
for the use of lesser-known but more suitable ion-pair alternatives to TEA for
many oligonucleotide sequences. Graphical Abstract ?.
PMID- 28405941
TI - Public knowledge and behaviours concerning antibiotic use and resistance in
France: a cross-sectional survey.
AB - PURPOSE: To evaluate knowledge and behaviours concerning antibiotics and
bacterial resistance in the French population, and to identify the socio
demographic factors associated with a high level of such knowledge and
appropriate behaviours. METHODS: A survey of the general population was conducted
in 2015 in northeast France. The 44-item standardized questionnaire used
comprised three parts, focusing on the assessment of knowledge, behaviours, and
the collection of main socio-demographic characteristics of respondents (gender,
age, having children, education level, and profession). The association of these
characteristics with the level of knowledge about antibiotics, and with related
behaviours, as well as the association between knowledge and behaviours was
identified in a bivariate analysis (Chi-2 tests) and a multivariate analysis when
necessary (logistic regression). RESULTS: The 200 respondents had quite a good
level of knowledge about antibiotics for several points: the lack of
effectiveness of antibiotics for colds (75.5%), the risk of inefficacy of
antibiotics when misused (93%), and the effects of overconsumption on bacterial
resistance (92%). Conversely, the effects of different doses and treatment
durations on resistance were less well known. Inappropriate behaviours were
frequent, especially non-adherence to dosing schedules and to treatment duration
(35.5%), and self-medication practices (18%). Female gender, older age, and
having children were independently associated with a good level of knowledge. A
low level of education and older age were associated with appropriate behaviours.
CONCLUSIONS: No association was found between knowledge and behaviours,
highlighting the relevance of national public information campaigns to limit the
misuse of antibiotics.
PMID- 28405942
TI - First Successful Conception Induced by a Male Cystinosis Patient.
AB - Cystinosis is a rare autosomal recessive lysosomal storage disease characterized
by multi-organ cystine accumulation, leading to renal failure and extra-renal
organ dysfunction. Azoospermia of unknown origin is the main cause of infertility
in all male cystinosis patients. Although spermatogenesis has shown to be intact
at the testicular level in some patients, no male cystinosis patient has been
reported yet to have successfully induced conception.We present the first
successful conception ever reported, induced by a 27-year-old male renal
transplant infantile nephropathic cystinosis patient through percutaneous
epididymal sperm aspiration (PESA) followed by intracytoplasmatic sperm injection
(ICSI). After 36 weeks and 6 days of an uncomplicated pregnancy, a dichorial
diamniotic (DCDA) twin was born with an appropriate weight for gestational age
and in an apparently healthy status. Moreover, we demonstrate that the sperm of
epididymal origin in selected male cystinosis patients can be viable for inducing
successful conception.Our observation opens a new perspective in life for many
male cystinosis patients whom nowadays have become adults, by showing that
despite azoospermia fathering a child can be realized. In addition, our findings
raise questions about the possibility of sperm cryopreservation at a young age in
these patients.
PMID- 28405943
TI - Myocardial oxidative stress correlates with left ventricular dysfunction on
strain echocardiography in a rodent model of sepsis.
AB - BACKGROUND: Recognition of cardiomyopathy in sepsis can be challenging due to the
limitations of conventional measures such as ejection fraction (EF) and
fractional shortening (FS) in the context of variable preload and afterload
conditions. This study correlates myocardial function using strain
echocardiography (SE) with cardiomyocyte oxidative stress in a murine model of
sepsis. METHODS: C57BL/6J mice were randomized into control (n = 10), sham (n =
25), and a cecal ligation and puncture (CLP) (n = 33) model of sepsis.
Echocardiography was performed pre-, 12, 24, and 48 h post-injury. Cardiac pro
inflammatory cytokines and mitochondrial redox scavenger expression were
evaluated in a subset of each arm. To evaluate the influence of redox scavenger
upregulation on oxidative injury and cardiac function, CLP was performed on
mitochondrial catalase-upregulated C57BL/6J MCAT+/+ mice (n = 12) and wild-type
(WT) animals for comparison. RESULTS: Septic C57BL/6J mice exhibited depressed
longitudinal strain (LS) when compared to sham and control at 24 h (p < 0.01) and
48 h (p = 0.04) post-CLP despite having a preserved EF. Furthermore, there was a
significant association between increased odds of mortality and depressed LS (OR
= 1.23, p = 0.04). Septic C57BL/6J mice concomitantly demonstrated increased
expression of cardiomyocyte pro-inflammatory cytokines and decreased expression
of redox scavengers at 24 and 48 h. When comparing C57Bl/6 MCAT +/+ mice and
C57BL/6J WT mice, a significant decrease in LS was identified in the WT mice at
24 h (MCAT = -23 +/- 5% vs. WT = -15 +/- 4% p < 0.01) and 48 h (MCAT = -23 +/- 7%
vs. WT = -15 +/- 4.3% p = 0.04) post-CLP which correlated with significant
increase in the level of cardiac oxidative stress following CLP. CONCLUSIONS: In
this sepsis model, SE identified cardiomyopathy despite normal EF. SE depression
temporally coincides with upregulation of inflammatory cytokines and decreases
expression of key mitochondrial ROS scavengers. Upregulation of redox scavenger
(CAT) abrogates oxidative stress and cardiac dysfunction in this sepsis model.
PMID- 28405944
TI - Clinical Relevance of Differences in Glomerular Filtration Rate Estimations in
Frail Older People by Creatinine- vs. Cystatin C-Based Formulae.
AB - BACKGROUND: The risk of incorrect medication dosing is high in frail older
people. Therefore, accurate assessment of the glomerular filtration rate is
important. OBJECTIVE: The objective of this study was to compare the estimated
glomerular filtration rate using creatinine- and cystatin C-based formulae, the
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in frail
older people. We hypothesized that frailty determines the difference between the
creatinine- and cystatin C-based formulae. METHODS: The mean difference between
CKD-EPI creatinine and cystatin C was determined using (cross-sectional) data of
55 patients (mean age 73 years) admitted to a psychiatric ward for older adults.
The level of agreement of these estimations was assessed by a Bland-Altman
analysis. In all patients, the Rockwood's Frailty Index was derived and
correlated with the mean difference between CKD-EPI creatinine and cystatin C.
RESULTS: The mean difference between CKD-EPI creatinine (mean 71.2 mL/min/1.73
m2) and CKD-EPI cystatin C (mean 57.6 mL/min/1.73 m2) was 13.6 mL/min/1.73 m2 (p
< 0.0001). The two standard deviation limit in the Bland-Altman plot was large
(43.2 mL/min/1.73 m2), which represents a low level of agreement. The Frailty
Index did not correlate with the mean difference between the creatinine- and
cystatin C-based glomerular filtration rate (Pearson correlation coefficient
0.182, p = 0.184). CONCLUSIONS: There was a significant gap between a creatinine-
and cystatin C-based estimation of glomerular filtration rate, irrespective of
frailty. The range of differences between the commonly used estimated glomerular
filtration rate formulae might result in clinically relevant differences in drug
prescription and differences in chronic kidney disease staging.
PMID- 28405945
TI - The Comparative Risk of Delirium with Different Opioids: A Systematic Review.
AB - OBJECTIVE: There is substantial evidence that the use of opioids increases the
risk of adverse outcomes such as delirium, but whether this risk differs between
the various opioids remains controversial. In this systematic review, we evaluate
and discuss possible differences in the risk of delirium from the use of various
types of opioids in older patients. METHODS: We performed a search in MEDLINE by
combining search terms on delirium and opioids. A specific search filter for use
in geriatric medicine was used. Quality was scored according to the quality
assessment for cohort studies of the Dutch Cochrane Institute. RESULTS: Six
studies were included, all performed in surgical departments and all
observational. No study was rated high quality, one was rated moderate quality,
and five were rated low quality. Information about dose, route, and timing of
administration of the opioid was frequently missing. Pain and other important
risk factors of delirium were often not taken into account. Use of tramadol or
meperidine was associated with an increased risk of delirium, whereas the use of
morphine, fentanyl, oxycodone, and codeine were not, when compared with no
opioid. Meperidine was also associated with an increased risk of delirium
compared with other opioids, whereas tramadol was not. The risk of delirium
appeared to be lower with hydromorphone or fentanyl, compared with other opioids.
Numbers used for comparisons were small. CONCLUSION: Some data suggest that
meperidine may lead to a higher perioperative risk for delirium; however, high
quality studies that compare different opioids are lacking. Further comparative
research is needed.
PMID- 28405946
TI - New Generation of Three-Dimensional Tools to Learn Anatomy.
AB - We present a new generation tool based of interactive 3D models. This models are
based on the radiological two-dimensional images by computed tomography imaging.
Our article focuses on the anatomical region of the skull base. These new three
dimensional models offer a wide field of application in the learning, as they
offer multiple visualization tools (rotation, scrolling, zoom...). In this way,
understanding of the anatomical region is facilitated. A feature to be dismissed
is that a professional workstation is not required to work with three-dimensional
models, since a personal computer can be viewed and interacted with the models.
Educational and clinical applications are also discussed.
PMID- 28405947
TI - Accuracy and Reliability of Infrared Thermography in Assessment of the Breasts of
Women Affected by Cancer.
AB - Evaluate reliability and accuracy of infrared thermography in the assessment of
women wth breasts cancer. Thirty-five participants had unilateral breast cancer
and 17 control subjects were assessed using infrared thermography. To evaluate
reliability, two professionals, who were experienced, measured the temperature of
the infrared images in two different moments, with a one-week interval. Biopsy
was used as a gold standard exam with regard identify breast cancer. The analysis
illustrated excellent reliability in terms of the affected, contralateral and
control breasts with the intra-class correlation coefficient values ranging from
0.948 to 0.999. Standard measurement error ranged from 0.04 to 0.28 degrees C,
and minimum detectable change deviated from 0.11 to 0.78 degrees C. Moreover,
low to moderate accuracy were observed in terms of the establishment of the
breast cancer diagnosis with values of the area under the receiver operating
characteristic (ROC) curve ranging from 0.571 and 0.749. Breasts affected by
cancer present higher skin temperature compared to contralateral and control.
Furthermore, excellent reliability of the analysis of the infrared images and low
moderate accuracy in terms diagnosis were observed. Considering the results,
infrared thermography can be applied as an instrument complement the assessment
of breast cancer patients, but not for diagnostic purposes.
PMID- 28405948
TI - A De-Identification Pipeline for Ultrasound Medical Images in DICOM Format.
AB - Clinical data sharing between healthcare institutions, and between practitioners
is often hindered by privacy protection requirements. This problem is critical in
collaborative scenarios where data sharing is fundamental for establishing a
workflow among parties. The anonymization of patient information burned in DICOM
images requires elaborate processes somewhat more complex than simple de
identification of textual information. Usually, before sharing, there is a need
for manual removal of specific areas containing sensitive information in the
images. In this paper, we present a pipeline for ultrasound medical image de
identification, provided as a free anonymization REST service for medical image
applications, and a Software-as-a-Service to streamline automatic de
identification of medical images, which is freely available for end-users. The
proposed approach applies image processing functions and machine-learning models
to bring about an automatic system to anonymize medical images. To perform
character recognition, we evaluated several machine-learning models, being
Convolutional Neural Networks (CNN) selected as the best approach. For accessing
the system quality, 500 processed images were manually inspected showing an
anonymization rate of 89.2%. The tool can be accessed at
https://bioinformatics.ua.pt/dicom/anonymizer and it is available with the most
recent version of Google Chrome, Mozilla Firefox and Safari. A Docker image
containing the proposed service is also publicly available for the community.
PMID- 28405949
TI - Transoral endoscopic thyroidectomy: preliminary experience in Italy.
AB - Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a feasible
novel surgical procedure that does not need visible incisions. We describe our
initial experience with TOETVA. We recruited 15 patients who were willing to
undergo TOETVA. Inclusion criteria were (a) patients who had a neck ultrasound
(US) with a estimated thyroid diameter not larger than 10 cm; (b) US estimated
gland volume <=45 mL; (c) nodule size <=50 mm; (d) a benign tumor, such as a
thyroid cyst, single-nodular goiter, or multinodular goiter; (e) follicular
neoplasm; (f) papillary microcarcinoma without evidence of metastasis. The
procedure is carried out through a three-port technique placed at the oral
vestibule, one 10-mm port for 30 degrees endoscope and two additional 5-mm ports
for dissecting and coagulating instruments. CO2 insufflation pressure is set at 6
mmHg. An anterior cervical subplatysmal space is created from the oral vestibule
down to the sternal notch, laterally to the sternocleidomastoid muscle.
Thyroidectomy is done fully endoscopically using conventional endoscopic
instruments and intraoperative neuromonitoring. There were 34% total
thyroidectomies and 66% hemithyroidectomies. All TOETVA procedures were performed
successfully with no conversions. The mean operative time was 87.6 (59-118) min
for lobectomy and 107.6 (99-135) min for bilateral procedure. We observed one
case of transient postoperative hypocalcemia. There was no recurrent laryngeal
nerve palsy. The cosmetic result was excellent in all patients. This is the first
case series of TOETVA in Italy. TOETVA may provide a method for ideal cosmetic
results. The results are encouraging, and we are optimistic about the future
expansion of its applicability.
PMID- 28405950
TI - ItSURG: a challenge for surgical research in Italy.
PMID- 28405951
TI - Posterior retroperitonoscopic adrenalectomy; a back door access with an unusually
rapid learning curve.
AB - Posterior retroperitonoscopic adrenalectomy (PRA) has become a standard approach
to the adrenal gland. The aim of this study was to report an initial experience
with the procedure following a proper preparatory phase highlighting the
rapidity, safety and effectiveness by which it could be introduced into a
surgeon's practice. Between May 2015 and July 2016, 14 PRAs were performed in 14
patients (9 females and 5 males). The average age was 46 years, BMI: 25.5 kg/m2,
and ASA score: 2. Indications included: incidenatloma (n = 5), Conn's adenoma (n
= 5), and Cushing's adenoma (n = 4). Lesions were on average 3.3 cm in size.
Outcomes of interest included: operative time (OT), conversion rate,
postoperative morbidity and mortality rates, and the length of hospital stay.
Mean OT was 87.5 min (range 35-150 min). A significant reduction in OT occurred
after the sixth procedure and was progressive thereafter. After the tenth case,
the OT became less than 1 h. No conversion was required. No intra- or post
operative complications occurred, and mortality was zero. All patients commenced
oral intake and ambulated following full recovery from anesthesia. The mean
length of hospital stay was 3 days (range 2-6 days). PRA offers a direct access
to the adrenal gland allowing for target-oriented dissection. Cognitive
reorientation to the anatomy of this back door access and an adequate learning
curve could be rapidly achieved by experienced and properly prepared laparoscopic
surgeons.
PMID- 28405952
TI - Surgical management of papillary thyroid carcinoma: an overview.
AB - The surgical management of papillary thyroid carcinoma remains contentious and
the optimal surgical strategy has not been yet established. The extent of thyroid
resection has been the nub of this debate. Literature lacks prospective
randomized controlled trials that could help put this debate to rest, and these
have been labeled as being impractical. Consequently, large retrospective studies
and expert opinion have constituted the basis of clinical practice guidelines.
Recent American Thyroid Association and National Comprehensive Cancer Network
guidelines consider a conservative approach in the form of a thyroid lobectomy
sufficient for low-risk disease and that total thyroidectomy remains the standard
of care in the presence of high-risk features. Nevertheless, many authorities
still advocate more aggressive therapy for low-risk disease. The challenge in
standardizing the surgical strategy to papillary thyroid carcinoma is mainly
related to a major tumor characteristic: the high frequency of occult cancerous
foci whether within the thyroid gland itself or within loco-regional lymph nodes
as this tumor characteristic has been incriminated for a higher risk of recurrent
disease and its adverse sequelae. The purpose of this article is to provide an
overview of the surgical management of papillary thyroid carcinoma and the main
arguments surrounding this hotly debated topic. All evidences for this review
article were drawn from PubMed articles in English language mostly cross
referenced with international guideline statements.
PMID- 28405953
TI - Angioedema in the emergency department: a practical guide to differential
diagnosis and management.
AB - BACKGROUND: Angioedema is a common presentation in the emergency department (ED).
Airway angioedema can be fatal; therefore, prompt diagnosis and correct treatment
are vital. OBJECTIVE OF THE REVIEW: Based on the findings of two expert panels
attended by international experts in angioedema and emergency medicine, this
review aims to provide practical guidance on the diagnosis, differentiation, and
management of histamine- and bradykinin-mediated angioedema in the ED. REVIEW:
The most common pathophysiology underlying angioedema is mediated by histamine;
however, ED staff must be alert for the less common bradykinin-mediated forms of
angioedema. Crucially, bradykinin-mediated angioedema does not respond to the
same treatment as histamine-mediated angioedema. Bradykinin-mediated angioedema
can result from many causes, including hereditary defects in C1 esterase
inhibitor (C1-INH), side effects of angiotensin-converting enzyme inhibitors
(ACEis), or acquired deficiency in C1-INH. The increased use of ACEis in recent
decades has resulted in more frequent encounters with ACEi-induced angioedema in
the ED; however, surveys have shown that many ED staff may not know how to
recognize or manage bradykinin-mediated angioedema, and hospitals may not have
specific medications or protocols in place. CONCLUSION: ED physicians must be
aware of the different pathophysiologic pathways that lead to angioedema in order
to efficiently and effectively manage these potentially fatal conditions.
PMID- 28405954
TI - Genetic Testing in Pediatric Epilepsy.
AB - PURPOSE OF REVIEW: This article summarizes the emerging landscape of pediatric
epilepsy, highlighting genetic contributions, and reviews approaches to genetic
evaluation for pediatric epilepsy in this context. RECENT FINDINGS: Advances in
understanding the genetic basis for epilepsy over the last several years have
been due in large part to the identification of de novo genetic variation
underlying sporadic severe epilepsy in children; the genetic underpinnings of the
more common epilepsies remain largely unknown. Next-generation sequencing
approaches have been added to the repertoire of clinical tests for the evaluation
of pediatric epilepsy, improving our ability to make positive diagnoses. Yields
of over 50% are now being reported in selected groups of patients. Genetic
variation contributing to the risk for pediatric epilepsy spans continua of scale
and influence. The highest yield of genetic testing is currently in children with
sporadic severe epilepsy caused by de novo variation. The approach to genetic
evaluation and interpretation of results requires an understanding of (1) the
epilepsy phenotype and (2) the particular advantages and limitations of the
different genetic tests available. Our understanding of genetic variation will
continue to improve over time and "negative" results are best conceptualized as
"unresolved" or "negative for now."
PMID- 28405955
TI - Cutaneous adverse reaction during lithium treatment: a case report and updated
systematic review with meta-analysis.
AB - OBJECTIVES: To present a new case of adverse cutaneous reaction during lithium
treatment and to update the systematic review and meta-analysis of the incidence
of this adverse reaction. METHODS: We conducted a systematic search (performed in
September 2016) for peer-reviewed articles in English indexed in Medline (2011
present). Meta-analytical estimates were obtained using the "Metafor" package.
CASE PRESENTATION: Ms. H., a 31-year-old Caucasian woman with BD1, was admitted
to the inpatient unit for a full-blown psychotic episode and treated with
carbamazepine 400 mg q.d., lithium carbonate 450 mg q.d., and risperidone 4 mg
q.d. with clinical improvement. After 12 days from the start of
psychopharmacological treatment, she manifested a cutaneous reaction that
motivated the stop of carbamazepine treatment, as well as the increase in lithium
carbonate dose (750 mg q.d.). Risperidone dose remained unvaried. Since the skin
lesion persisted after 8 days from withdrawal of carbamazepine, the private
practitioner stopped also lithium carbonate treatment (de-challenge), maintaining
risperidone treatment. The cutaneous reaction resolved spontaneously after six
days from withdrawal of lithium carbonate. Subsequently, the worsening of
psychopathological conditions motivated a new admission during which lithium
carbonate was reintroduced (16 days after its suspension) (re-challenge). On the
following day, we observed an itching erythematous maculopapular rash involving
the trunk, the four limbs, and the oral mucosa. CONCLUSIONS: Our case of an
erythematous maculopapular rash during lithium treatment was the first to present
a challenge-de-challenge-re-challenge sequence that suggests causality. Although
meta-analysis does not point to an increased rate of adverse skin reaction during
lithium treatment, clinicians should not neglect to monitor cutaneous symptoms
during lithium treatment.
PMID- 28405956
TI - The impact of polypharmacy and drug interactions among the elderly population in
Western Sicily, Italy.
AB - AIM: Primary endpoint was to report polypharmacy distribution in the general
population vs >=65 years old people and to examine the frequency of drug-drug
interactions (DDIs) in the Health Local Unit of Palermo, Italy, in relationship
with patients' age. METHODS: Drug prescription data for the year 2014 were
extracted from the database of the Local Health Unit of Palermo Province, Italy.
Patients were divided into five age groups (0-13, 14-64, 65-69, 70-74, and >=75
year old). The detection of potential DDIs in polypharmacy profiles was performed
with NavFarma software (Infologic srl, Padova, Italia), with DDI classification
provided by tool Micromedex Drug Reax (Truven Health Analitics, Michigan, USA).
RESULTS: We analyzed data of 1,324,641 patients, and 15,801,191 medical
prescription were recorded; of these, 11,337,796 regarded chronic conditions. The
drug prescriptions reached the highest values in the 65-69 and 70-74 age groups
(p = 0.005 and p = 0.008 vs age 14-64 respectively). An overall amount of
6,094,373 DDIs were detected, of which 47,173 were contraindicated. Median number
of DDIs was higher in 65-69 and 70-74 age groups (p = 0.008 and p = 0.012 vs age
14-64, respectively). Regarding contraindicated DDIs a significant difference was
detected comparing 14-64 vs >=65 age groups (p = 0.010 vs 65-69 group, p = 0.005
vs 70-74 group and >=75 group). CONCLUSIONS: Polypharmacy is a phenomenon
acquiring increasing dimensions also in our province. It interests particularly
the older subjects, and assumes a dramatic accent when it is put in relationship
with the frequency of DDIs. A proactive vigilance about potential life
threatening drug interactions is mandatory.
PMID- 28405957
TI - Enhancing memory and imagination improves problem solving among individuals with
depression.
AB - Recent work has revealed links between memory, imagination, and problem solving,
and suggests that increasing access to detailed memories can lead to improved
imagination and problem-solving performance. Depression is often associated with
overgeneral memory and imagination, along with problem-solving deficits. In this
study, we tested the hypothesis that an interview designed to elicit detailed
recollections would enhance imagination and problem solving among both depressed
and nondepressed participants. In a within-subjects design, participants
completed a control interview or an episodic specificity induction prior to
completing memory, imagination, and problem-solving tasks. Results revealed that
compared to the control interview, the episodic specificity induction fostered
increased detail generation in memory and imagination and more relevant steps on
the problem-solving task among depressed and nondepressed participants. This
study builds on previous work by demonstrating that a brief interview can enhance
problem solving among individuals with depression and supports the notion that
episodic memory plays a key role in problem solving. It should be noted, however,
that the results of the interview are relatively short-lived.
PMID- 28405958
TI - Previously acquired cue-outcome structural knowledge guides new learning:
Evidence from the retroactive-interference-between-cues effect.
AB - The effect of retroactive interference between cues predicting the same outcome
(RIBC) occurs when the behavioral expression of a cue-outcome association (e.g.,
A->O1) is reduced due to the later acquisition of an association between a
different cue and the same outcome (e.g., B->O1). In the present experimental
series, we show that this effect can be modulated by knowledge concerning the
structure of these cue-outcome relationships. In Experiments 1A and 1B, a
pretraining phase was included to promote the expectation of either a one-to-one
(OtO) or a many-to-one (MtO) cue-outcome structure during the subsequent RIBC
training phases. We hypothesized that the adoption of an OtO expectation would
make participants infer that the previously learned A->O1 relationship would not
hold any longer after the exposure to B->O1 trials. Alternatively, the adoption
of an MtO expectation would prevent participants from making such an inference.
Experiment 1B included an additional condition without pretraining, to assess
whether the OtO structure was expected by default. Experiment 2 included control
conditions to assess the RIBC effect and induced the expectation of an OtO or MtO
structure without the addition of a pretraining phase. Overall, the results
suggest that participants effectively induced structural expectations regarding
the cue-outcome contingencies. In turn, these expectations may have potentiated
(OtO expectation) or alleviated (MtO expectation) the RIBC effect, depending on
how well these expectations could accommodate the target A->O1 test association.
This pattern of results poses difficulties for current explanations of the RIBC
effect, since these explanations do not consider the incidence of cue-outcome
structural expectations.
PMID- 28405959
TI - Subsidies to Increase Remote Pollution?
AB - During the last decade, Central Europe became a cynosure for the world for its
unparalleled public support for renewable energy. For instance, the production of
electricity from purpose-grown biomass received approximately twice the amount in
subsidies as that produced from biowaste. Moreover, the guaranteed purchase price
of electricity from solar panels was set approximately five times higher than
that from conventional sources. This controversial environmental donation policy
led to the devastation of large areas of arable land, a worsening of food
availability, unprecedented market distortions, and serious threats to national
budgets, among other things. Now, the first proposals to donate the purchase
price of electric vehicles (and related infrastructure) from national budgets
have appeared for public debate. Advocates of these ideas argue that they can
solve the issue of electricity overproduction, and that electric vehicles will
reduce emissions in cities. However, our analysis reveals that, as a result of
previous scandals, environmental issues have become less significant to local
citizens. Given that electric cars are not yet affordable for most people, in
terms of local purchasing power, this action would further undermine national
budgets. Furthermore, while today's electromobiles produce zero pollution when
operated, their sum of emissions (i.e. global warming potential) remains much
higher than that of conventional combustion engines. Therefore, we conclude that
the mass usage of electromobiles could result in the unethical improvement of a
city environment at the expense of marginal regions.
PMID- 28405960
TI - Outcome Measures of Adjustable Transobturator Male System with Pre-attached
Scrotal Port for Male Stress Urinary Incontinence After Radical Prostatectomy: A
Prospective Study.
AB - INTRODUCTION: The objective of this study was to report outcome measures with
third-generation pre-attached scrotal port adjustable transobturator male system
(ATOMS) for male stress urinary incontinence (SUI) after radical prostatectomy.
METHODS: A prospective open study was conducted on consecutive patients.
Evaluation included cough test, urethroscopy, filling and voiding cystometry, 24
h pad count and pad test, patient-reported outcomes (ICIQ-SF, IIQ-7, PGI, GRA,
and VAS), complications according to the Clavien-Dindo system, operative results,
number of adjustments, and filling of the system. RESULTS: Thirty-four patients
with median pad test 510 (170-1225) ml were operated on. Preoperative SUI was
mild (5.9%), moderate (17.6%), and severe (76.5%). At median 18.5 (12-26) months
follow-up distribution of SUI was none (85.3%), mild (8.8%), and moderate (5.9%).
Median intraoperative filling was 14 (8-17) ml, number of adjustments 1 (0-5),
and total filling 17.5 (11-33.5) ml. At 3 months, median ICIQ-SF (p = 0.0001) and
IIQ-7 (p < 0.0001) decreased. At 12 months, 24-h pad count and pad test decreased
(both p < 0.0001), residual volume slightly increased (p = 0.018), PGI-I was 1 (1
3), GRA 6 (3-6), and 97% were satisfied with treatment. Continence (p = 0.016)
and satisfaction (p = 0.09) were worse in irradiated patients. Median operative
time was 67 (35-120) min, hospital stay 1 (1-3) days, and VAS for pain on
postoperative day 1 was 0 (0-2). Complications presented in 14.7% (8.8% grade I
and 5.9% grade III). CONCLUSION: Treatment of severe male SUI after radical
prostatectomy with pre-attached scrotal port ATOMS is safe and very effective in
the short term. A positive cough test before implant and intraoperative
overfilling of the system may optimize patient selection and results.
PMID- 28405961
TI - Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer
Patients Receiving Ceritinib: A Chart Review Study.
AB - INTRODUCTION: This study aimed to provide the first real-world description of the
characteristics, treatments, dosing patterns, and early outcomes of patients with
ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US
clinical practice. METHODS: US oncologists provided data from medical charts of
adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC
who received ceritinib following crizotinib. Patient characteristics, treatment
patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal
adverse events (AEs) by dose and instructions on food intake were assessed, and
Kaplan-Meier analysis was used to describe clinician-defined progression-free
survival (PFS) on ceritinib. RESULTS: Medical charts of 58 ALK-positive NSCLC
patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21%
with prior chemotherapy experience). At ceritinib initiation, 44 patients had
multiple distant metastases, most commonly in the liver (60%), bone (53%), and
brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and
10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8
months), most patients achieved either a complete or partial response (69%) on
ceritinib, regardless of metastatic sites present at initiation or initial dose.
Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal
AE reported during follow-up. The majority of events occurred in patients
instructed to fast; no patients instructed to take a lower dose of ceritinib with
food reported gastrointestinal AEs. CONCLUSION: These early findings of ceritinib
use in clinical practice suggest that ceritinib is effective at treating
crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic
sites or initial dose, and dosing ceritinib with food may lead to fewer
gastrointestinal AEs. Future studies with larger sample size and longer follow-up
are warranted, including an ongoing randomized trial to assess the
gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals.
FUNDING: Novartis Pharmaceutical Corporation.
PMID- 28405962
TI - Discrimination Fully Mediates the Effects of Incarceration History on Depressive
Symptoms and Psychological Distress Among African American Men.
AB - AIM: Using a nationally representative sample of African American men, this study
investigated the associations between lifetime history of incarceration,
discrimination, and mental health (e.g., depressive symptoms and psychological
distress). We hypothesized that discrimination would fully mediate the
association between incarceration history and mental health outcomes among
African American men. METHODS: Using a cross-sectional design, our analysis
included 1271 African American men who participated in the National Survey of
American Life (NSAL), 2001-2003. Incarceration history was the main independent
variable. Depressive symptoms and psychological distress were the dependent
variables. Everyday discrimination was the mediator. Age, education, and income
were covariates. Structural equation models (SEMs) were used for data analysis.
RESULTS: Among African American men, incarceration history was positively
associated with perceived discrimination, depressive symptoms, and psychological
distress. Everyday discrimination fully mediated the associations between
incarceration history and both depressive symptoms and psychological distress.
CONCLUSION: Discrimination may play an important role in the mental health
problems of African American men with a history of incarceration. These findings
have public policy implications as well as clinical implications for mental
health promotion of African American men. Policies that reduce preventable
incarceration or at least reduce subsequent discrimination for those who have
been incarcerated may enhance mental health of previously incarcerated African
American men.
PMID- 28405963
TI - Multidimensional Investigation of Bedrock Heterogeneity/Unconformities at a DNAPL
Impacted Site.
AB - Organic solvent (i.e., dense nonaqueous phase liquid, DNAPL) migration in the
subsurface is known to be extremely sensitive to geologic heterogeneity. There is
often a focus on heterogeneity that results from changing depositional conditions
over short spatial scales. Similar or even more extreme spatial heterogeneity can
result postdeposition due to erosional processes. This study applies a
synergistic approach based on a combination of high-resolution lithologic logs of
continuous cores, borehole geophysical logs, surface electrical resistivity, and
seismic refraction tomography models to assess spatial heterogeneity in a shallow
bedrock sequence subject to multiple unconformities and contaminated with a
mixture of organic chemicals. The persistence of DNAPL in the source zone and an
associated dissolved-phase plume led to variable impacts on formation resistivity
across the study site. Seismic refraction in combination with electrical
resistivity tomography improved interpretation of highly irregular erosional
boundaries by delineating sharp lateral transitions in lithologic composition
near the source zone and across the dissolved-phase plume. Electrical resistivity
was effective at differentiating between clean and mud-rich sandstones and their
unconformable contact with an underlying dolostone. Geophysical measurements
revealed eroded dolostone mounds encased by a network of younger mud-rich
sandstones channelized by clean semi-lithified sand, all of which was buried
beneath variable glacial drift. Our synergistic multidimensional approach
resulted in the development of a detailed three-dimensional shallow bedrock
geospatial model, which has led to an improved understanding of DNAPL migration
and contaminant plume heterogeneity.
PMID- 28405964
TI - The neuroscience of people watching: how the human brain makes sense of other
people's encounters.
AB - Neuroscientific investigations interested in questions of person perception and
impression formation have traditionally asked their participants to observe and
evaluate isolated individuals. In recent years, however, there has been a surge
of studies presenting third-party encounters between two (or more) individuals as
stimuli. Owing to this subtle methodological change, the brain's capacity to
understand other people's interactions and relationships from limited visual
information--also known as people watching--has become a distinct topic of
inquiry. Though initial evidence indicates that this capacity relies on several
well-known networks of the social brain (including the person-perception network,
the action-observation network, and the mentalizing network), a comprehensive
framework of people watching must overcome three major challenges. First, it must
develop a taxonomy of judgments that people habitually make when witnessing the
encounters of others. Second, it must clarify which visual cues give rise to
these encounter-based judgments. Third, it must elucidate how and why several
brain networks work together to accomplish these judgments. To advance all three
lines of research, we summarize what is currently known as well as what remains
to be studied about the neuroscience of people watching.
PMID- 28405965
TI - Bayesian regression for group testing data.
AB - Group testing involves pooling individual specimens (e.g., blood, urine, swabs,
etc.) and testing the pools for the presence of a disease. When individual
covariate information is available (e.g., age, gender, number of sexual partners,
etc.), a common goal is to relate an individual's true disease status to the
covariates in a regression model. Estimating this relationship is a nonstandard
problem in group testing because true individual statuses are not observed and
all testing responses (on pools and on individuals) are subject to
misclassification arising from assay error. Previous regression methods for group
testing data can be inefficient because they are restricted to using only initial
pool responses and/or they make potentially unrealistic assumptions regarding the
assay accuracy probabilities. To overcome these limitations, we propose a general
Bayesian regression framework for modeling group testing data. The novelty of our
approach is that it can be easily implemented with data from any group testing
protocol. Furthermore, our approach will simultaneously estimate assay accuracy
probabilities (along with the covariate effects) and can even be applied in
screening situations where multiple assays are used. We apply our methods to
group testing data collected in Iowa as part of statewide screening efforts for
chlamydia, and we make user-friendly R code available to practitioners.
PMID- 28405966
TI - Pointwise influence matrices for functional-response regression.
AB - We extend the notion of an influence or hat matrix to regression with functional
responses and scalar predictors. For responses depending linearly on a set of
predictors, our definition is shown to reduce to the conventional influence
matrix for linear models. The pointwise degrees of freedom, the trace of the
pointwise influence matrix, are shown to have an adaptivity property that
motivates a two-step bivariate smoother for modeling nonlinear dependence on a
single predictor. This procedure adapts to varying complexity of the nonlinear
model at different locations along the function, and thereby achieves better
performance than competing tensor product smoothers in an analysis of the
development of white matter microstructure in the brain.
PMID- 28405967
TI - Frailty, functional decline and mortality in hospitalized older adults.
PMID- 28405968
TI - Comment on "Asian collaboration to establish a provisional system to provide high
quality end-of-life care by promoting advance care planning for the elderly".
PMID- 28405969
TI - Establishment of a new medical school in the Tohoku region after the Great East
Japan Earthquake.
PMID- 28405970
TI - Usefulness of chair stand time as a surrogate of gait speed in diagnosing
sarcopenia.
PMID- 28405971
TI - Response to the letter of Dr Tomoyuki Kawada, "Chronic kidney disease, physical
frailty and cognitive impairment".
PMID- 28405972
TI - Chronic kidney disease, physical frailty and cognitive impairment.
PMID- 28405973
TI - To recognize fall related psychological concern should not lead to neglect other
psychomotor consequences of falls.
PMID- 28405974
TI - Cut-off point for chair stand time when used as a surrogate for gait speed in
sarcopenia diagnosis.
PMID- 28405977
TI - 57th ANNUAL MEETING AND EXHIBITION.
PMID- 28405975
TI - Case report of severe iron deficiency anemia caused by proton pump inhibitor in
an elderly patient.
PMID- 28405978
TI - AMERICAN ASSOCIATION OF PHYSICISTS IN MEDICINE 57TH ANNUAL MEETING AND
EXHIBITION.
PMID- 28405979
TI - NEW AND EXCITING FEATURES THIS YEAR ....
PMID- 28405980
TI - NEW MEMBER SYMPOSIUM.
PMID- 28405981
TI - Reproductive Issues in Women with Systemic Lupus Erythematous.
PMID- 28405982
TI - India in Grip of Dengue - Yet Again.
PMID- 28405983
TI - Reproductive Health in Systemic Lupus Erythematosus, An experience from
Government Hospital in Western India.
AB - AIM: Systemic lupus erythematosus is an autoimmune disease which affects the
reproductive health of women pertaining to disease or its treatment. However,
Indian data is limited. Objective is to study menstrual disturbances and maternal
and fetal outcome during pregnancy in SLE patients. METHODS: This retrospective
and prospective observational study was conducted for a period of 18 months from
March 2012 to September 2013 in a tertiary care hospital in Mumbai. The study
included serial recruitment of SLE patients fulfilling inclusion criteria.
RESULTS: Out of 52 patients studied, 13(25%) developed amenorrhea; 10 of them
reversed and 3 patients developed premature menopause (5.77%). The higher mean
age (30 years or more) at initiation of Cyclophosphamide therapy was associated
with higher incidence of irreversible amenorrhea and this difference was
statistically significant (p=0.0001). Out of 16 SLE pregnancies in 16 different
patients, 9 pregnancies were successful while 7 were unsuccessful including
IUFDs, abortions and maternal mortality. The incidence of successful pregnancies
was significantly higher in low disease activity group (6/N=6, 100%) when
compared to high disease activity group (3/N=10, 30%) (p=0.0114). CONCLUSIONS:
High disease activity and Cyclophosphamide therapy are the two most important
factors causing amenorrhea in SLE patients. Cyclophosphamide therapy when
initiated in patients older than 30 years can lead to irreversible amenorrhea.
Successful pregnancy is possible even in lupus nephritis patients if disease is
well controlled at the time of conception.
PMID- 28405984
TI - A Prospective Study of Acute Kidney Injury According to KDIGO Definition and its
Mortality Predictors.
AB - BACKGROUND: Acute kidney injury is no longer considered to be an innocent
bystander merely reflecting co-existent pathologies but an independent risk
factor for mortality in the ICU. AIMS AND OBJECTIVES: To study clinical profile
and correlation of patients with acute kidney injury (AKI) according to KDIGO
definition with respect to incidence, outcome and different causes of AKI in
critical care unit. STUDY DESIGN AND SETTING: It is a prospective observational
study; and was carried out in the ICU of a tertiary care, teaching, public
hospital. MATERIAL AND METHODS: We studied 316 patients developing AKI in ICU
over a period of 1 year. RESULTS AND CONCLUSION: Incidence of AKI in our ICU was
37.71% and mortality rate was 51.9%. Tropical Acute febrile illnesses followed by
sepsis were the most common causes of AKI in ICU. Most common cause of AKI among
tropical acute febrile illnesses (AFI) was malaria and among sepsis group was
lung infection. In our study KDIGO staging could not predict outcome because
majority of patients had multisystem failure. Pre-existing co-morbidities, multi
organ system failure were associated with high mortality. APACHE II scoring
system under- predicted the mortality in patients with AKI.
PMID- 28405985
TI - Clinical Profile and Complications of Scrub Typhus: Hospital-Based Study in Sub
Himalayan Region.
AB - BACKGROUND: Scrub typhus is a documented disease in Himachal Pradesh, but there
have been no clinico-epidemiological studies in this area. The present study is
done with IgM ELISA as a diagnostic test which has higher sensitivity and
specificity as most of previous studies had used Weil Felix test as a diagnostic
test. METHODOLOGY: This was a prospective observational study. All the patients
more than 18 years of age with positive IgM ELISA for scrub typhus with or
without eschar were included. The clinical profile was observed. IgM scrub typhus
was done by kit method manufactured by InBios International, Inc. RESULTS: Total
330 patients were observed. Maximum patients were observed in August, September,
and October. Fever was the most common presenting complaint. Eschar was present
in 40.61% patients. Complications were seen in 71.2 %. CONCLUSIONS: The general
physicians should be sensitized for the early diagnosis to reduce mortality.
PMID- 28405986
TI - Assessment of Compliance to Treatment of Diabetes and Hypertension amongst
Previously Diagnosed Patients from Rural Community of Raigad District of
Maharashtra.
AB - INTRODUCTION: Substantial burden of diabetes and hypertension is on rise in
India, leading to a twin epidemic. India, being a rural country, has unique
problems regarding the treatment compliance which is a serious risk for morbidity
and mortality. OBJECTIVE: To assess the compliance to treatment of hypertension
and diabetes amongst the diagnosed patients from rural area and to study reasons
of non-compliance and knowledge and attitude. MATERIAL AND METHODS: Community
based, cross sectional, observational study conducted in the rural communities of
Tara and Barapada villages of Raigad district of Maharashtra. Survey was
conducted covering population of 2115 across 360 families, 250 at Barapada and
110 at Tara. All the cases of diabetes and hypertension diagnosed for more than
one year were included. A structured and pre-tested questionnaire was
administered including details on demography, medical documentation, treatment
details and factors assessing the compliance, knowledge and attitude towards the
diseases. RESULTS: When reviewed the treatment adherence pattern based on
documentary evidence and interview of the patient, on history of taking
medication strictly since the detection illness, it was found that more than 70%
of the Diabetics and more than 75% of the Hypertensive have discontinued the
treatment in between. The most common reasons of non-compliance is the lack of
sufficient motivation for treatment adherence as many mentioned (61.4% diabetics,
55.8% hypertensives) difficulty to remember to take daily medication due to work
or forgetfulness. This is followed by lack of money (50%diabetics, 55.8%
hypertensives) and living far away from doctor in city (43% diabetics and 46%
hypertensives). CONCLUSIONS: The study findings are only tip of iceberg and the
non-adherence to the treatment of diabetes and hypertension in rural population
is at alarmingly high. Illiteracy, lack of faith in treatment and motivation,
unawareness and self-neglect as well as financial constraints and lack of
specialist care in rural area is playing important role.
PMID- 28405987
TI - Cardiorenal Syndrome: Clinical Outcome Study.
AB - BACKGROUND: Over recent years, the field of medicine has been challenged by the
twin epidemic of heart failure and renal insufficiency. The coexistence of the
two problems in the same patient, referred to as cardiorenal syndrome (CRS), is
defined as 'disorders of the heart and kidneys whereby acute or chronic
dysfunction in one organ may induce acute or chronic dysfunction of the other.
The mechanisms underlying this interaction are complex and multifactorial in
nature. OBJECTIVE OF STUDY: Identify and classify patients admitted with
cardiorenal syndrome into various subtypes and assess clinical outcome at
discharge and at three months. METHODS: Ours was a longitudinal study of 50
patients admitted in ICU with CRS. They were classified as per RONCO
classification (2008) into various subtypes. Outcomes was addressed as favourable
for patients stable at discharge and at 3 months follow up, whereas outcome was
termed non-favourable for patients who expired or initiated on hemodialysis.
RESULTS: Of 50 patients, two-third patients were males (66%), with mean age of
males and females being 64.18 years and 64.64 years respectively. Majority of the
patients had Type-1 CRS (46%) followed by twenty two percent Type-2, twenty six
percent type-4 and six percent Type-5. There were no patients with type-3 CRS. At
the end of the study, 24 (48%) patients were stable, 12 (24%) required dialysis
and 14 (28%) patients had expired. The total non-favourable outcomes (dialysis /
death) were higher with subtypes CRS-4 (n-11, 22%) and CRS-1 (n-8, 16%). Anemia,
raised serum creatinine, low eGFR values, low ejection fraction were significant
predictors of non-favourable outcome in our study. CONCLUSIONS: CRS occurs in all
age groups, more commonly in elderlies with a male preponderance. Prevalence of
CRS-1 was higher followed by CRS-4. Prognosis was unfavourable in CRS-1, CRS-4
and CRS-5. Sepsis was predominant cause of death in patients with CRS-5 with
hundred percent mortality during hospital stay. Risk factors like pre-existing
renal impairment, anemia, reduced e GFR and low ejection fraction were
significantly associated with worse outcomes. There is need for large scale
population / community based studies to chart the prevalence of cardiorenal
subtypes and prognosticate each individually.
PMID- 28405989
TI - Liver Transplantation - What the Physician Should Know?
PMID- 28405988
TI - A Study of salt and fat Consumption pattern in Regional Indian diet among
hypertensive and dyslipidemic PaTients - SCRIPT study.
AB - BACKGROUND: Cardiovascular diseases are leading cause of mortality and morbidity.
There is an increasing prevalence of hypertension and dyslipidemia due to
globalization and adoption of westernized dietary habits in India. These
transitions are manifest in dietary patterns and health outcomes. OBJECTIVE: To
study the dietary salt and fat intake among patients diagnosed with hypertension
and dyslipidemia in India. METHODS: SCRIPT study was a pilot exploratory, cross
sectional, observational, descriptive, multi-center study. It was conducted
across hospitals and clinics in five metro cities of India, represented into four
regional zones. In each region (North, n = 113; East, n = 98; West, n = 83;
South, n = 152), patients diagnosed with hypertension and dyslipidemia were
enrolled in the study. Socio-demographic and treatment details were recorded.
Participants were interviewed by a dietician and their dietary intake was
assessed by a three-day recall of food item questionnaire/ food diary. RESULTS:
Overall the mean total daily salt consumption was 10.9 grams. Region-wise, the
mean daily salt consumption in North, East, West and South were 14.13, 9.81,
10.12 and 9.38 grams respectively. The daily salt consumption in the North was
significantly higher than other regions (P=0.012). The daily consumption of
saturated fats (total saturated fat, ghee and butter) in the North was higher and
statistically significantly in comparison to West, South and East (P <0.05).
Overall, fats contributed to 24.1%, proteins contributed to 12.7% and
carbohydrate contributed to 63.2% of total energy per day. The percentage of fat
and protein contributing to total energy per day was within the acceptable range.
CONCLUSIONS: Our study documented higher dietary salt intake than that
recommended in India. There is an urgent need to address the issue of high salt
and saturated fat consumption. Nutritional strategies for reducing salt intake,
saturated fat and balancing energy nutrients should be urgently applied in Indian
hypertensive and dyslipidemia patients.
PMID- 28405990
TI - Measures of Association.
PMID- 28405991
TI - Bilateral Reversible Diffusion Weighted MRI Abnormalities in Transient Global
Amnesia.
PMID- 28405992
TI - 'Chik' Sign in Chikungunya Fever.
PMID- 28405993
TI - Floating Aorta Sign.
PMID- 28405994
TI - Vertical Transmission of Chikungunya Manifesting as Foetal Pericardial Effusion.
AB - Chikungunya fever is believed to be a self-limiting illness, which can result in
significant disability, but with a very low mortality. Chikungunya is uncommonly
believed to be associated with serious manifestations. The present case is of a
pregnant lady who had transient fever for two days in the third trimester,
following which she developed foetal pericardial effusion and intrauterine growth
restriction. After two weeks of the fever, in view of non-reactive non-stress
test, breech and foetal pericardial effusion, patient was taken up for caesarean
section. The neonate was positive for Chikungunya, detected by RT-PCR, while the
mother tested positive for Chikungunya IgM antibodies. A diagnosis of Chikungunya
pericardial effusion was made in the neonate, presumably acquired vertically
secondary to the maternal Chikungunya infection occurring in the third trimester,
which was also contributory to intrauterine growth restriction. No case of
vertical transmission of Chikungunya has been reported in India, and foetal
pericardial effusion has not been reported in world literature.
PMID- 28405995
TI - Recurrent Ventricular Tachycardia Due to Long QT Syndrome.
AB - Long QT syndrome (LQTS) is a rare inherited heart condition in which delayed
repolarization of the heart following a heartbeat, increases the risk of episodes
of Torsades de pointes (TdP, a form of irregular heartbeat that originates from
the ventricles). These episodes may lead to palpitations, fainting, and sudden
death due to ventricular fibrillation. Episodes may be provoked by various
stimuli, depending on the subtype of the condition. We are reporting a case of 37
years old male whom we diagnosed to have long QT syndrome on the basis of
clinical and ECG findings.
PMID- 28405996
TI - Ebstein's Anomaly with Paradoxical Embolism to Lower Limb.
AB - Ebstein's anomaly (EA) is a rare congenital heart disease. Paradoxical embolism
(PDE) may occur in EA due to associated atrial septal defect (ASD). An 18 year
old male with EA presented with left lower limb ischemia due to PDE to the limb.
No features of cerebral embolism was present. PDE is a potential complication of
EA. High level of awareness is needed for early diagnosis of PDE in EA to save a
limb in case of embolism to the extremity.
PMID- 28405998
TI - Disseminated Rhinosporidiosis Masquerading as Sarcoma.
AB - Rhinosporidiosis, though reported from several countries, has the highest
incidence in India (notably South India) and Sri Lanka, with most cases
presenting as nasal polyps. Nasopharynx and palpebral conjunctiva account for 85%
of the sites. Other mucosal sites affected are oropharynx, larynx, rectum and
external genitalia. Disseminated rhinosporidiosis is usually associated with
mucosal lesions. Rhinosporidiosis affecting skin, subcutaneous tissue and bone
are uncommon. Herein we report a rare case of disseminated rhinosporidiosis
mimicking a soft tissue sarcoma.
PMID- 28405997
TI - Tracheoesophageal Fistula following Endotracheal Intubation for Organophosphorus
Poisoning.
AB - Tracheoesophageal fistula (TEF) is an abnormal communication between the trachea
and esophagus. Iatrogenic TEF can be due to endotracheal intubation, rigid
bronchoscopy or tracheostomy. Tracheostomy tube cuff volumes and pressures
require constant monitoring to avoid tracheal injury. Acquired TEF which occurs
after prolonged intubation, usually develops after 15-200 days of mechanical
ventilation. We report a case of a large TEF secondary to endotracheal intubation
for organophosphorus poison-induced respiratory failure. Patient presented with
dysphagia and recurrent aspiration pneumonia after extubation. She underwent
trachea-esophageal fistulectomy and closure with a sternocleidomastoid muscle
flap.
PMID- 28405999
TI - Near Fatal Poisoning by Isoniazid and Rifampicin.
AB - Since six decades, Isoniazid and Rifampicin are used as first line drugs for
treatment of tuberculosis. The minimum acute lethal or toxic dose of Rifampicin
is not well established. However, non-fatal acute overdoses in adults have been
reported with doses ranging from 9 to 12 gm and fatal acute overdoses with doses
ranging from 14 to 60 gm. Isoniazid, if acutely ingested, even 1.5 to 2 gram may
cause toxicity in adults. We report a case of Pott's spine on ATT, who took
massive overdose of Rifampicin (>18 gm) and Isoniazid (>12 gm) and reported late
(almost 36 hours) after ingestion. He was treated successfully with pyridoxine,
hemodialysis and supportive care.
PMID- 28406001
TI - Disabling Osteopetrosis in an Young Lady.
AB - Osteopetrosis is a rare disorder of osteoclastic bone resorption leading to
hyperostosis. Albers-Schonberg disease, an autosomal dominant variant of
osteopetrosis occurs in young adults and has a benign course. A 17 year old
female presented with generalized weakness and pallor for last two months. She
had insidious onset and gradually progressive loss of vision and hearing for last
two years. Plain x-ray of skull revealed increased radio-opacity of skull bones
specially in the base, severe under-pneumatization of frontal and sphenoidal
sinuses. Maxillary and ethmoid sinuses were also opaque and under-pneumatised.
Bone scintigraphy with technetium-99m methylene diphosphonate showed diffusely
increased uptake in whole skull. Bone marrow biopsy revealed a reactive marrow
with areas of fibrosis without any evidence of granuloma or malignancy. The case
had cranial entrapment neuropathies and severe anaemia due to osteopetrosis. High
level of awareness is needed to diagnose the case properly and to help the
patient to cope with the disabling features of the disease.
PMID- 28406000
TI - Hidradenitis Suppurativa Complicating Epithelial Malignancy in Immunocompromised
Patient.
AB - Hidradenitis suppurativa complicating epithelial malignancy in people living with
HIV is very rare. Hidradenitis suppurativa is very rare seen in only 1% of
general population and 4% of young adults. We report a case of Hidradenitis
suppurativa complicating an epithelial malignancy in are immunocompromised (HIV
reactive) patient.
PMID- 28406002
TI - Asymptomatic Presentation of Large Cardiac Ball.
AB - A 45 years female presented with short duration of dry cough and atypical chest
pain. Chest X ray showed cardiomegaly with a bulge at the right heart border and
curvilinear calcification in left upper abdomen. Transthoracic echocardiography
(TTE) revealed a cystic lesion in the right ventricle free wall causing
compression of right atrial and ventricular cavity. Cardiac CT confirmed this
cyst as hydatid cyst. Patient underwent successful excision of right ventricular
hydatid cyst.
PMID- 28406003
TI - Pericardial Effusion with Cardiac Tamponade as a form of presentation of Primary
Hypothyroidism.
AB - Hypothyroidism is a rare cause of pericardial effusion (PE). Pericardial effusion
secondary to hypothyroidism remains a diagnostic challenge for clinicians because
of its inconsistency between symptoms and amount of pericardial effusion. We
report an atypical case that presented with ascites and was diagnosed to have
cardiac tamponade secondary to primary hypothyroidism. Besides repeated
pericardiocentesis she eventually required surgical management and optimization
of medical therapy to manage the massive pericardial effusion.
PMID- 28406004
TI - Papaya Leaves in Dengue.
PMID- 28406005
TI - Behcet's Disease Dilemma!
PMID- 28406006
TI - Organic Field-Effect Transistors with Macroporous Semiconductor Films as High
Performance Humidity Sensors.
AB - In this study, we designed and fabricated a high-performance humidity sensor
based on a donor-acceptor polymer transistor. To improve its sensing performance,
a polymeric semiconductor film with macroporous structure was prepared using a
facilitated phase-separation method. The relationship between the sensing
performance and the pore size was systematically investigated by testing the
humidity-sensing performance. The results suggested that the sensitivity of the
sensor was improved with increasing pore size within a certain range. The sensor
based on the macroporous film with an average pore size of 154 nm exhibited a
sensitivity of 415 and a response time of 0.68 s, as the low relative humidity
(RH) changed from 32% RH (9146 ppm) to 69% RH (20 036 ppm). These sensitivity
values are better than those obtained by other reported humidity sensors based on
organic field-effect transistors.
PMID- 28406007
TI - Adsorption of Uranium over NH2-Functionalized Ordered Silica in Aqueous
Solutions.
AB - The aim of this work was to obtain an in-depth understanding of the U(VI)
adsorption mechanism over amino-functionalized mesoporous silica SBA-15 and
highlights its high efficiency in aqueous media for U(VI) removal and
preconcentration. The samples were synthesized and functionalized by both
grafting and co-condensation methods, using different alkyl-substituted amine
groups and were characterized using X-ray diffraction, N2 physisorption, Fourier
transform infrared spectroscopy, and elemental C-H-N-S analyses. The properties
for U(VI) adsorption were evaluated under discontinuous conditions, with the
determination of the effect of several parameters (initial pH, contact time,
initial U(VI) concentration, functionalization method, and organic moiety
composition). U(VI) adsorption over grafted materials reached equilibrium at
around 30 min, with a maximum adsorption capacity of 573 mgU.gads-1 for the most
efficient material at its optimal adsorption pH (equal to 6) at 20 degrees C.
Functionalized materials by grafting exhibit better adsorption capacities than co
condensed samples because of higher function surface density and function
availability. U(VI) adsorption mechanisms were also studied by measuring the
electrophoretic mobilities of the particles, aqueous U(VI) speciation, in situ
attenuated total reflection infrared and Raman spectroscopies, and transmission
electron microscopy analysis. U(VI) adsorption occurred through the formation of
an inner sphere complex. The localization of adsorbed U(VI) has also been
determined inside of the mesopores, with the formation of several particles on
the nanometer scale, in the size of U-hydroxy phases. Besides, the study of the
reusability of amino-functionalized SBA-15 by applying adsorption-desorption
cycles was also conducted. The adsorption capacity of the material remains stable
for at least four adsorption-desorption cycles without any noticeable capacity
decrease.
PMID- 28406008
TI - Fabrication of Embedded Silver Nanowires on Arbitrary Substrates with Enhanced
Stability via Chemisorbed Alkanethiolate.
AB - We propose a versatile yet practical transferring technique to fabricate a high
performance and extremely stable silver nanowire (AgNW) transparent electrode on
arbitrary substrates. Hydroxylated poly(ethylene glycol) terephthalate (PET) or
poly(dimethylsiloxane) (PDMS) deposited with AgNWs was selectively decorated to
lower its polar surface energy, so that the AgNWs were easily and efficiently
transferred into an epoxy resin (EPR) as a freestanding film (AgNWs-EPR) or onto
various substrates. The AgNWs-EPR capped with alkanethiolate monolayers exhibits
high conductivity, low roughness, ultraflexibility, and strong corrosion
resistance. Using the transferring process, AgNWs-EPR was successfully
constructed on rough, adhesive, flimsy, or complex curved substrates, including
PET, thin optically clear adhesive, papers, a beaker, convex spherical PDMS, and
leaves. A flexible touch panel enabling multitouch and a curved transparent
heater on a beaker were first fabricated by using the composite film. These
demonstrations suggest that the proposed technique for AgNWs is a promising
strategy toward the next generation of flexible/portable/wearable electronics.
PMID- 28406009
TI - Centimeter-Scale Deposition of Mo0.5W0.5Se2 Alloy Film for High-Performance
Photodetectors on Versatile Substrates.
AB - Because of their great potential for academic investigation and practical
application in next-generation optoelectronic devices, ternary layered
semiconductors have attracted considerable attention in recent years. Similar to
the applications of traditional layered materials, practical applications of
ternary layered semiconductor alloys require the synthesis of large-area samples.
Here, we report the preparation of centimeter-scale and high-quality Mo0.5W0.5Se2
alloy films on both a rigid SiO2/Si substrate and a flexible polyimide (PI)
substrate. Then, photodetectors based on these alloy films are fabricated, which
are capable of conducting broad-band photodetection from ultraviolet to near
infrared region (370-808 nm) with high performance. The photodetector on SiO2/Si
substrates demonstrates a high responsivity (R) of 77.1 A/W, an outstanding
detectivity (D*) of 1.1 * 1012 Jones, and a fast response time of 8.3 ms. These
figures-of-merit are much superior to those of the counterparts of binary
material-based devices. Moreover, the photodetector on PI substrates also
achieves high performance (R = 63.5 A/W, D* = 3.56 * 1012 Jones). And no apparent
degradation in the device properties is observed even after 100 bending cycles.
These results make Mo0.5W0.5Se2 alloy a highly qualified candidate for next
generation optoelectronic applications.
PMID- 28406010
TI - Dimensional-Hybrid Structures of 2D Materials with ZnO Nanostructures via pH
Mediated Hydrothermal Growth for Flexible UV Photodetectors.
AB - Complementary combination of heterostructures is a crucial factor for the
development of 2D materials-based optoelectronic devices. Herein, an appropriate
solution for fabricating complementary dimensional-hybrid nanostructures
comprising structurally tailored ZnO nanostructures and 2D materials such as
graphene and MoS2 is suggested. Structural features of ZnO nanostructures
hydrothermally grown on graphene and MoS2 are deliberately manipulated by
adjusting the pH value of the growing solution, which will result in the
formation of ZnO nanowires, nanostars, and nanoflowers. The detailed growth
mechanism is further explored for the structurally tailored ZnO nanostructures on
the 2D materials. Furthermore, a UV photodetector based on the dimensional-hybrid
nanostructures is fabricated, which demonstrates their excellent photocurrent and
mechanical durability. This can be understood by the existence of oxygen
vacancies and oxygen-vacancies-induced band narrowing in the ZnO nanostructures,
which is a decisive factor for determining their photoelectrical properties in
the hybrid system.
PMID- 28406011
TI - Palladium-Catalyzed Oxidative Carbonylation of Aryl Hydrazines with CO and O2 at
Atmospheric Pressure.
AB - Palladium-catalyzed aerobic oxidative aminocarbonylation and alkoxycarbonylation
reactions with aryl hydrazines as coupling partners have been developed. The
oxidative carbonylation of aryl hydrazines proceeded smoothly at atmospheric
pressure CO, employing molecular oxygen as the terminal oxidant. The only
byproducts were nitrogen gas and water for both reactions. Notably, no double
carbonylation was detected. Furthermore, aryl-halogen bonds, which are normally
reactive in conventional Pd-catalyzed carbonylation reactions, remained intact.
PMID- 28406012
TI - Immunomodulatory Magnetic Microspheres for Augmenting Tumor-Specific Infiltration
of Natural Killer (NK) Cells.
AB - The purpose of this research is to develop magnetic resonance imaging (MRI)
visible immunomodulatory microspheres (IMM-MS) for efficient image guided cancer
immunotherapy. IMM-MS composed of recombinant interferon gamma (IFN-gamma), iron
oxide nanocubes (IONC), and biodegradable poly(lactide-co-glycolide) (PLGA) were
successfully prepared via a double-emulsion method. The prepared IMM-MS exhibited
a sustained IFN-gamma release and highly sensitive MR T2 contrast effects.
Finally, in an orthotopic liver tumor VX2 rabbit model, successful hepatic intra
arterial (IA) transcatheter delivery of IMM-MS to liver tumors was confirmed with
MR images. The deposition of IMM-MS significantly increased NK-cell infiltration
into the liver tumor site.
PMID- 28406013
TI - Exploiting Uniformly 13C-Labeled Carbohydrates for Probing Carbohydrate-Protein
Interactions by NMR Spectroscopy.
AB - NMR of a uniformly 13C-labeled carbohydrate was used to elucidate the atomic
details of a sugar-protein complex. The structure of the 13C-labeled Manalpha(1
2)Manalpha(1-2)ManalphaOMe trisaccharide ligand, when bound to cyanovirin-N (CV
N), was characterized and revealed that in the complex the glycosidic linkage
torsion angles between the two reducing-end mannoses are different from the free
trisaccharide. Distances within the carbohydrate were employed for conformational
analysis, and NOE-based distance mapping between sugar and protein revealed that
Manalpha(1-2)Manalpha(1-2)ManalphaOMe is bound more intimately with its two
reducing-end mannoses into the domain A binding site of CV-N than with the
nonreducing end unit. Taking advantage of the 13C spectral dispersion of 13C
labeled carbohydrates in isotope-filtered experiments is a versatile means for a
simultaneous mapping of the binding interactions on both, the carbohydrate and
the protein.
PMID- 28406014
TI - Sequence-Modulated Interactions between Single Multivalent DNA-Conjugated Gold
Nanoparticles.
AB - DNA-conjugated gold nanoparticle (AuNP) is an attractive building block to
construct elegant plasmonic nanomaterials by self-assembly but the complicated
interaction between multivalent nanoconjugates governing the assembly process and
the properties of assembled structures remains poorly understood. Herein, with an
in situ kinetic single-particle imaging method, we report the dynamic interaction
between single multivalent DNA-conjugated AuNPs quantitatively depends on the
nucleic acid sequence in nanoconjugates. From the binding dynamics analysis, it
was found that the binding of nanoconjugates with DNA length longer than nine
bases is kinetically irreversible and the binding rate is dependent on both the
sequence length and GC content, enabling us to predict the rational modulation of
binding rates of individual building blocks for stepwise assembly. Moreover, the
reversibility for the multivalent interaction between single nanoconjugates at
constant temperature can be reinstated by adopting the DNA sequence with single
nucleotide mismatch and the lifetime for nanoconjugates at bound state can be
tailored by changing the mismatch positions in DNA strands, providing new
opportunity to create active nanostructures with controlled dynamic properties.
All these findings provide new insights for understanding the multivalent
interaction during the assembly process at the single-nanoconjugate level and
predicting the programmable self-assembly of engineered nanoconjugates for the
fabrication of dynamic nanomaterials.
PMID- 28406015
TI - Imaging of a Thin Oxide Film Formation from the Combination of Surface
Reflectivity and Electrochemical Methods.
AB - Electrochemical methods (cyclic voltammetry (CV), potential steps, and
electrochemical impedance spectroscopy) were successfully combined with in situ
reflectometry measurements for a detailed analysis of the passive layer evolution
as a function of the electrode potential. Interestingly, both EIS and surface
reflectivity allowed a film thickness in the nanometer range to be readily
determined. In addition, transient analyses of the reflectivity simultaneously
recorded with CVs show the formation of both Fe2O3 and Fe3O4 oxides. The image
analysis showed that the steel surface reactivity is heterogeneous and presents
micrometric islands coated with a thicker oxide layer than the surrounding
surface. The in situ combination of these techniques thus offers a powerful
analytical description of the interface on a local scale and its transient
response to a perturbation.
PMID- 28406016
TI - Luminescent Cyclometalated Gold(III) Alkyl Complexes: Photophysical and
Photochemical Properties.
AB - A series of luminescent cyclometalated gold(III) complexes having alkyls as
auxiliary ligands has been prepared. The alkyl ligand was found to effectively
increase the emission quantum yields and lifetimes of luminescent cyclometalated
gold(III) complexes by circumventing the population of LLCT excited states that
are found in complexes supported by arylacetylide ligands. These gold(III) alkyl
complexes exhibit emission quantum yields and lifetimes of up to 0.40 and 180
MUs, respectively, in solution at room temperature. The triplet emission color of
these complexes is tunable from yellow to sky blue by modifying the
cyclometalating ligand.
PMID- 28406017
TI - Templated Self-Assembly of a Covalent Polymer Network for Intracellular Protein
Delivery and Traceless Release.
AB - Trafficking proteins inside cells is an emerging field with potential utility in
basic cell biology and biological therapeutics. A robust and sustainable delivery
strategy demands not only good protection of the cargo but also reversibility in
conjugation and activity. We report a protein-templated polymer self-assembly
strategy for forming a sheath around the proteins and then tracelessly releasing
them in the cytosol. The versatility of the approach, demonstrated here, suggests
that the strategy is compatible with a wide array of biologics.
PMID- 28406018
TI - Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling
Oxidation Strategy.
AB - A concise and scalable second generation synthesis of HIV maturation inhibitor
BMS-955176 is described. The synthesis is framed by an oxidation strategy
highlighted by a CuI mediated aerobic oxidation of betulin, a highly selective
PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement
which occurs through a unique reaction mechanism for the installation of the C17
amino functionality. The synthetic route proceeds in 7 steps with 47% overall
yield and begins from the abundant and inexpensive natural product betulin.
PMID- 28406020
TI - Toward Rational Design of Oxide-Supported Single-Atom Catalysts: Atomic
Dispersion of Gold on Ceria.
AB - We have constructed a general thermodynamic model of chemical potentials and
applied ab initio electronic structure and molecular dynamics simulations, as
well as kinetic Monte Carlo analysis, to probe the dynamical, reactive, and
kinetic aspects of metal single-atom catalysts (SACs) on oxide support. We choose
Au single atoms (SAs) supported on ceria as a typical example to demonstrate how
our model can guide the rational design of highly stable and reactive SACs. It is
shown that, under realistic conditions, various factors such as temperature,
pressure, particle size, and the reducibility of the support can strongly affect
both the stability and the reactivity of SACs by altering the relative chemical
potentials between SAs and metal nanoparticles (NPs). The Au SAs at step sites of
ceria support are rather stable, even at temperatures as high as 700 K, and
exhibit around 10 orders of magnitude more reactivity for CO oxidation than the
terrace sites. Remarkably, under reaction conditions, Au SAs can be dynamically
created at the interface of small-size Au NPs on ceria support even without step
sites, which accounts for the puzzling significant size effect in gold catalysis.
Our work underscores an unrecognized critical role of Au SAs in gold
nanocatalysis and provides a general methodology for designing the metal SACs on
oxide supports.
PMID- 28406019
TI - Honey Extracted Polyphenolics Reduce Experimental Hypoxia in Human Keratinocytes
Culture.
AB - Hypoxic assault affects fundamental cellular processes and generates oxidative
stress on healthy cells/molecules. Honey extracted polyphenolics (HEP) as a
natural antioxidant reduced hypoxic cytotoxicity in this study. Different honey
samples were physicochemically characterized to identify preferred (jamun) honey
[pH 3.55 +/- 0.04, conductivity (MUs/cm) = 6.66 +/- 0.14, water content % (w/w) =
14.70 +/- 0.35, total solid content % (w/w) = 85.30 +/- 0.35, phenol content (mg
GAE/100 g) = 403.55 +/- 0.35, flavonoid content (mg QE/100 g) = 276.76 +/- 4.10,
radical scavenging activity (% 500 MUL) = 147.75 +/- 3.13, catalase activity
(absorbance at 620 nm) = 0.226 +/- 0.01]. HEP was tested in different doses on
hypoxic and normoxic cells (HaCaT) using viability and antioxidant assays.
Cardinal molecular expressions such as cadherin-catenin-cytoskeleton complex
(namely, E-cadherin, beta-catenin, and F-actin), hypoxia marker (Hif 1 alpha),
proliferation marker (Ki67), and epithelial master regulator (p63) were studied
by immuno-cytochemisty (ICC) and qRT-PCR. The 0.063 mg/mL HEP demonstrated better
vitality and functionality of HaCaT cells as per viability assay (*, P < 0.01)
even under hypoxia. ICC and qRT-PCR observations indicated restoration of
cellular survival and homeostasis under 0.063 mg/mL HEP after hypoxic assault.
Furthermore, major spectral changes for nucleic acid and membrane phospholipid
reorganizations by Fourier transform infrared spectroscopy illustrated a positive
impact of 0.063 mg/mL HEP on hypoxic cells considering proliferation and cellular
integrity. It was concluded that a specific dose of jamun HEP reduces hypoxic
cytotoxicity.
PMID- 28406021
TI - The Nup62 Coiled-Coil Motif Provides Plasticity for Triple-Helix Bundle
Formation.
AB - The central transport channel of the vertebrate nuclear pore complex (NPC)
consists of nucleoporins: Nup62, Nup54, and Nup58. The coiled-coil domains in
alpha-helical regions of these nucleoporins are thought to be crucial for several
protein-protein interactions in the NPC subcomplexes. In this study, we
determined the crystal structure of the coiled-coil domain of rat Nup62 fragment
(residues 362-425) to 2.4 A resolution. The crystal structure shows the conserved
coiled-coil domain as a parallel three-helix bundle for the Nup62(362-425)
fragment. On the basis of our size exclusion chromatography coupled to multiangle
light scattering analysis and glutaraldehyde cross-linking experiments, we
conclude that the Nup62(362-425) fragment displays dynamic behavior in solution
and can also exist in either homodimeric or homotrimeric states. Our comparative
analysis of the rat Nup62(362-425) homotrimeric structure with previously
reported heterotrimeric structures [rat Nup62(362-425).Nup54(346-407) and Xenopus
Nup62(358-485).Nup54(315-450).Nup58(283-406) complexes] demonstrates the
structural basis for parallel triple-helix bundle formation for Nup62 with
different partners. Moreover, we show that the coiled-coil domain of Nup62 is
sufficient for interaction with the coiled-coil domain of rat Exo70, a protein in
an exocyst complex. On the basis of these observations, we suggest the plausible
chain replacement mechanism that yields to diverse protein assemblies with Nup62.
In summary, the coiled-coil motif present in Nup62 imparts the ability to form a
homotrimer and heterotrimers either with Nup54 or with Nup54-Nup58 within the
NPCs as well as with Exo70 beyond the NPCs. These complexes of Nup62 suggest the
crucial role of the coiled-coil motifs in providing plasticity to various modular
assemblies.
PMID- 28406022
TI - The Performance of Nanoparticulate Graphitic Carbon Nitride as an Amphiphile.
AB - Graphitic carbon nitride (g-C3N4), a polymeric semiconductor that finds potential
applications in multiple areas, is shown to feature amphiphilic behavior. Since
the feasibility of g-C3N4 aqueous colloids is well-established, g-C3N4 can be
viewed as an effective and well-accessible colloidal amphiphile. Its activity at
different interfaces (liquid-liquid, liquid-solid, and liquid-air) is
illustrated: g-C3N4 is able to stabilize Pickering emulsions formed by water and
organic solvents, and also, gas-filled g-C3N4 frameworks based on those emulsions
are obtained by natural drying. Hydrophobic solid substances like graphite and
carbon nanotubes are smoothly dispersed in water assisted by g-C3N4. Besides,
networklike g-C3N4 membranes floating on a water surface are created and can be
readily transferred to substrates. These findings provide many opportunities for
the processing of g-C3N4-containing functional materials and devices.
PMID- 28406023
TI - Sequential Order of the Secondary Structure Transitions of Proteins under
External Perturbations: Regenerated Silk Fibroin under Thermal Treatment.
AB - Whether the process of protein folding/unfolding is fully cooperative or it
contains sequential elements has long been a fundamental issue in protein
science. This issue seemingly became straightforward since the appearance of
generalized two-dimensional (2D) correlation spectroscopy in 1990s, because 2D
correlation analysis has been considered as a convenient and powerful analytical
tool to determine the sequential order of events under external physical or
chemical perturbations. In this work, the sequential order of the secondary
structure transitions of regenerated silk fibroin under thermal treatment from
130 to 220 degrees C was first studied using generalized 2D correlation
spectroscopy, but an apparently doubtful sequential order was obtained; beta
sheet was the first one to change at low temperature, then the random coil,
followed by the nonamide C?O and, finally, the alpha-helix. A subsequent detailed
in situ infrared spectral analysis showed that the main secondary structures of
silk fibroin, including alpha-helix, beta-turn, random coil and beta-sheet (high
wavenumber component), all changed with a fully cooperative manner at a
relatively low temperature of 150 degrees C. But the low-wavenumber component of
beta-sheet started to change at a higher temperature of 180 degrees C. Besides,
it has also been found that, before 200 degrees C, the loss of alpha-helix and
random coil was transformed into beta-turn, beta-sheet, and nonamide C?O. After
200 degrees C, some beta-turn structure was also disruptured and transformed
into beta-sheet and nonamide C?O.
PMID- 28406024
TI - Catalytic Stereodivergent Synthesis of Steroid-Fulleropyrrolidine Hybrids.
AB - The diastereoselective synthesis of cis and trans steroid-fulleropyrrolidines
hybrids by reaction of N-metalated azomethine ylides [Cu(II) or Ag(I)] with the
appropriate chiral ligand and C60 is described. The experimental findings reveal
that the azomethine ylide stabilized by an allylic group cycloadds to
[60]fullerene in an efficient manner and with a good diastereomeric excess.
Furthermore, the new generated stereocenters are fully controlled by the
catalytic systems used without being influenced by the chirality of the steroid.
Interestingly, by this synthetic methodology the each one of the four possible
stereoisomers have efficiently been obtained and characterized by CD spectra.
PMID- 28406025
TI - Biogenic Nanoselenium Particles Effectively Attenuate Oxidative Stress-Induced
Intestinal Epithelial Barrier Injury by Activating the Nrf2 Antioxidant Pathway.
AB - In the present study, a new form of selenium nanoparticle (biogenic nanoselenium
(BNS) particles) was synthesized using bacteria. The protection of BNS particles
against oxidative stress-induced intestinal barrier dysfunction and the inherent
mechanisms of this process were investigated, and selenomethionine (SeMet) and
chemically synthesized nanoselenium (Nano-Se) particles were used for comparison.
Characterization of BNS particles revealed that they were monodispersed and
homogeneous spheres, with an average size of 139.43 +/- 7.44 nm. In the mouse
model of intestinal oxidative stress, BNS particles were found to protect the
mouse intestinal barrier function and preserve intestinal redox homeostasis more
efficiently than SeMet and Nano-Se. In vitro experiments with porcine jejunum
epithelial (IPEC-J2) cells verified the stronger epithelial barrier-protecting
effect of BNS particles against oxidative stress, with reduced cell apoptosis and
an improved cell redox state. BNS activated the nuclear factor (erythroid-derived
2)-like 2 (Nrf2) and increased the expression of its downstream genes, including
thioredoxin reductase (TXNRD)-1, NADPH dehydrogenase (NQO)-1, heme oxygenase (HO)
1, and thioredoxin (Trx), in dose- and time-dependent manners. In contrast, SeMet
and Nano-Se merely enhanced the activity of the selenoenzymes TXNRD-1 and
glutathione peroxidase (GPx)-1, indicating the role of selenium donors. Moreover,
the knock down of Nrf2 significantly blocked the antioxidative effect of BNS,
confirming that BNS protects the intestinal barrier from oxidative stress-induced
damage by activating Nrf2 and its downstream genes. Our results suggest that BNS
is a promising selenium species with potential application in treating oxidative
stress-related intestinal diseases.
PMID- 28406026
TI - Multiple-Color-Generating Cu(In,Ga)(S,Se)2 Thin-Film Solar Cells via Dichroic
Film Incorporation for Power-Generating Window Applications.
AB - There are four prerequisites when applying all types of thin-film solar cells to
power-generating window photovoltaics (PVs): high power-generation efficiency,
longevity and high durability, semitransparency or partial-light transmittance,
and colorful and aesthetic value. Solid-type thin-film Cu(In,Ga)S2 (CIGS) or
Cu(In,Ga)(S,Se)2 (CIGSSe) PVs nearly meet the first two criteria, making them
promising candidates for power-generating window applications if they can
transmit light to some degree and generate color with good aesthetic value. In
this study, the mechanical scribing process removes 10% of the window CIGSSe thin
film solar cell with vacant line patterns to provide a partial-light-transmitting
CIGSSe PV module to meet the third requirement. The last concept of creating
distinct colors could be met by the addition of reflectance colors of one
dimensional (1D) photonic crystal (PC) dichroic film on the black part of a
partial-light-transmitting CIGSSe PV module. Beautiful violets and blues were
created on the cover glass of a black CIGSSe PV module via the addition of 1D PC
blue-mirror-yellow-pass dichroic film to improve the aesthetic value of the
outside appearance. As a general result from the low external quantum efficiency
(EQE) and absorption of CIGSSe PVs below a wavelength of 400 nm, the harvesting
efficiency and short-circuit photocurrent of CIGSSe PVs were reduced by only ~10%
without reducing the open-circuit voltage (VOC) because of the reduced overlap
between the absorption spectrum of CIGSSe PV and the reflectance spectrum of the
1D PC blue-mirror-yellow-pass dichroic film. The combined technology of partial
vacancy-scribed CIGSSe PV modules and blue 1D PC dichroic film can provide a
simple strategy to be applied to violet/blue power-generating window
applications, as such a strategy can improve the transparency and aesthetic value
without significantly sacrificing the harvesting efficiency of the CIGSSe PV
modules.
PMID- 28406027
TI - Gelatin-Derived Graphene-Silicate Hybrid Materials Are Biocompatible and
Synergistically Promote BMP9-Induced Osteogenic Differentiation of Mesenchymal
Stem Cells.
AB - Graphene-based materials are used in many fields but have found only limited
applications in biomedicine, including bone tissue engineering. Here, we
demonstrate that novel hybrid materials consisting of gelatin-derived graphene
and silicate nanosheets of Laponite (GL) are biocompatible and promote osteogenic
differentiation of mesenchymal stem cells (MSCs). Homogeneous cell attachment,
long-term proliferation, and osteogenic differentiation of MSCs on a GL-scaffold
were confirmed using optical microscopy and scanning electron microscopy. GL
powders made by pulverizing the GL-scaffold were shown to promote bone
morphogenetic protein (BMP9)-induced osteogenic differentiation. GL-powders
increased the alkaline phosphatase (ALP) activity in immortalized mouse embryonic
fibroblasts but decreased the ALP activity in more-differentiated immortalized
mouse adipose-derived cells. Note, however, that GL-powders promoted BMP9-induced
calcium mineral deposits in both MSC lines, as assessed using qualitative and
quantitative alizarin red assays. Furthermore, the expression of chondro
osteogenic regulator markers such as Runx2, Sox9, osteopontin, and osteocalcin
was upregulated by the GL-powder, independent of BMP9 stimulation; although the
powder synergistically upregulated the BMP9-induced Osterix expression, the
adipogenic marker PPARgamma was unaffected. Furthermore, in vivo stem cell
implantation experiments demonstrated that GL-powder could significantly enhance
the BMP9-induced ectopic bone formation from MSCs. Collectively, our results
strongly suggest that the GL hybrid materials promote BMP9-induced osteogenic
differentiation of MSCs and hold promise for the development of bone tissue
engineering platforms.
PMID- 28406029
TI - CO2-Water-Rock Wettability: Variability, Influencing Factors, and Implications
for CO2 Geostorage.
AB - Carbon geosequestration (CGS) has been identified as a key technology to reduce
anthropogenic greenhouse gas emissions and thus significantly mitigate climate
change. In CGS, CO2 is captured from large point-source emitters (e.g., coal
fired power stations), purified, and injected deep underground into geological
formations for disposal. However, the CO2 has a lower density than the resident
formation brine and thus migrates upward due to buoyancy forces. To prevent the
CO2 from leaking back to the surface, four trapping mechanisms are used: (1)
structural trapping (where a tight caprock acts as a seal barrier through which
the CO2 cannot percolate), (2) residual trapping (where the CO2 plume is split
into many micrometer-sized bubbles, which are immobilized by capillary forces in
the pore network of the rock), (3) dissolution trapping (where CO2 dissolves in
the formation brine and sinks deep into the reservoir due to a slight increase in
brine density), and (4) mineral trapping (where the CO2 introduced into the
subsurface chemically reacts with the formation brine or reservoir rock or both
to form solid precipitates). The efficiency of these trapping mechanisms and the
movement of CO2 through the rock are strongly influenced by the CO2-brine-rock
wettability (mainly due to the small capillary-like pores in the rock which form
a complex network), and it is thus of key importance to rigorously understand CO2
wettability. In this context, a substantial number of experiments have been
conducted from which several conclusions can be drawn: of prime importance is the
rock surface chemistry, and hydrophilic surfaces are water-wet while hydrophobic
surfaces are CO2-wet. Note that CO2-wet surfaces dramatically reduce CO2 storage
capacities. Furthermore, increasing pressure, salinity, or dissolved ion valency
increases CO2-wettability, while the effect of temperature is not well
understood. Indeed theoretical understanding of CO2-wettability and the ability
to quantitatively predict it are currently limited although recent advances have
been made. Moreover, data for real storage rock and real injection gas (which
contains impurities) is scarce and it is an open question how realistic
subsurface conditions can be reproduced in laboratory experiments. In conclusion,
however, it is clear that in principal CO2-wettability can vary drastically from
completely water-wet to almost completely CO2-wet, and this possible variation
introduces a large uncertainty into trapping capacity and containment security
predictions.
PMID- 28406028
TI - Water Distribution, Dynamics, and Interactions with Alzheimer's beta-Amyloid
Fibrils Investigated by Solid-State NMR.
AB - Water is essential for protein folding and assembly of amyloid fibrils. Internal
water cavities have been proposed for several amyloid fibrils, but no direct
structural and dynamical data have been reported on the water dynamics and site
specific interactions of water with the fibrils. Here we use solid-state NMR
spectroscopy to investigate the water interactions of several Abeta40 fibrils. 1H
spectral lineshapes, T2 relaxation times, and two-dimensional (2D) 1H-13C
correlation spectra show that there are five distinct water pools: three are
peptide-bound water, while two are highly dynamic water that can be assigned to
interfibrillar water and bulk-like matrix water. All these water pools are
associated with the fibrils on the nanometer scale. Water-transferred 2D
correlation spectra allow us to map out residue-specific hydration and give
evidence for the presence of a water pore in the center of the three-fold
symmetric wild-type Abeta40 fibril. In comparison, the loop residues and the
intramolecular strand-strand interface have low hydration, excluding the presence
of significant water cavities in these regions. The Osaka Abeta40 mutant shows
lower hydration and more immobilized water than wild-type Abeta40, indicating the
influence of peptide structure on the dynamics and distribution of hydration
water. Finally, the highly mobile interfibrillar and matrix water exchange with
each other on the time scale of seconds, suggesting that fibril bundling
separates these two water pools, and water molecules must diffuse along the
fibril axis before exchanging between these two environments. These results
provide insights and experimental constraints on the spatial distribution and
dynamics of water pools in these amyloid fibrils.
PMID- 28406030
TI - Three Different Reactions, One Catalyst: A Cu(I) PNP Pincer Complex as Catalyst
for C-C and C-N Cross-Couplings.
AB - An air-stable, thermally robust, and well-defined Cu(I) PNP pincer complex based
on the 2,6-diaminopyridine scaffold is described. This complex is an active
catalyst for the cross-couplings of a range of aryl and heteroaryl (including
benzoxazole, thiazole, pyridine, and thiophene) halides with different
organomagnesium reagents, alkynes, and aryl-amines giving excellent to good
isolated yields.
PMID- 28406031
TI - Iodine-Catalyzed C-N Bond Formation: Synthesis of 3-Aminoquinoxalinones under
Ambient Conditions.
AB - A metal-free cross-dehydrogenative coupling between quinoxalinones (sp2 C-H) and
amines (N-H) in the presence of catalytic iodine is reported. The reaction yields
3-aminoquinoxalinones in moderate to high yields under ambient conditions in
dioxane as solvent and aqueous tert-butyl hydroperoxide (TBHP) as the terminal
oxidant. The reaction is highly versatile and exhibits good functional group
tolerance with a range of primary and secondary amines. It provides a practical
access to pharmaceutically active 3-aminoquinoxalinone derivatives. Preliminary
mechanistic studies reveal in situ iodination of the amine as the putative mode
of activation.
PMID- 28406032
TI - Deposition of DNA Nanostructures on Highly Oriented Pyrolytic Graphite.
AB - We report the deposition of DNA origami nanostructures on highly oriented
pyrolytic graphite (HOPG). The DNA origami goes through a structural
rearrangement and the DNA base is exposed to interact with the graphite surface.
Exposure to ambient air, which is known to result in a hydrophilic-to-hydrophobic
wetting transition of HOPG, does not significantly impact the deposition yield or
the shape deformation of DNA nanostructures. The deposited DNA nanostructures
maintain their morphology for at least a week and promote site-selective chemical
vapor deposition of SiO2. This process is potentially useful for a range of
applications that include but are not limited to nanostructure fabrication,
sensing, and electronic and surface engineering.
PMID- 28406033
TI - The impact of HIV antiretroviral treatment perception on risky sexual behaviour
in Botswana: a short report.
AB - The aim of this article is to investigate the impact of ART perception on risky
sexual behaviours in Botswana. Using binary logistic regression analysis
controlling for individual characteristics, the results tend to support the
hypothesis that ART misconceptions do not necessarily increase risky sexual
behaviours. In particular, the study findings suggest the belief that ARVs cure
HIV and AIDS and that people on ARVs should not always use condoms do not
necessarily lead to increased risky sexual behaviours, particularly among women.
Gender differentials exist in the perceived sexual risk resulting from the use of
ART. Risky sexual behaviours increase for women who, wrongly, believed that ARVs
cure HIV and AIDS and people on ARVs should not always use condoms. Although
there is evidence to suggest ART perceptions do not necessarily lead to increased
risky sexual behaviours, HIV and AIDS prevention programmes are needed to
strengthen their information, education and communication intervention component
that can address misconceptions about ART treatment and provide correct
information that is gender-appropriate.
PMID- 28406034
TI - Analysis of "A New Optimized Percutaneous Access System for CIPII".
AB - While only used initially in cases with resistance to subcutaneous insulin
therapy, intraperitoneal insulin therapy provides an overall more stable glucose
control than subcutaneous insulin therapy thanks to its pharmacokinetics as
pointed by Garcia-Verdugo et al from the experience of implantable insulin pumps.
The expansion of these devices has been limited by underdelivery issues and high
cost. The availability of a new percutaneous access to intraperitoneal route
could allow a similar glucose control with less constraints of follow-up and
expected lower cost. Currently reported clinical experience does not allow a
reliable assessment of its main risk of infection which could impair its
sustained usability. Because intraperitoneal insulin could allow a fully
automated closed-loop insulin delivery, a specific interest for its means of
performance is relevant.
PMID- 28406035
TI - Diagnostic Accuracy of Random ECG in Primary Care for Early, Asymptomatic Cardiac
Autonomic Neuropathy.
AB - AIMS: Cardiac autonomic reflex tests (CARTs) are time consuming and require
patient cooperation for detecting cardiac autonomic neuropathy (CAN). Heart rate
variability (HRV) analysis requires less patient cooperation and is quicker to
complete. However the reliability of HRV results as a clinical tool, with respect
to length of recording and accuracy of diagnosis is inconclusive. The current
study investigated the reproducibility associated with varying length of
recording for early CAN (eCAN) assessment. METHODS: Participants were 68 males,
72 females with average age of 55 for controls and 63 for early CAN. Inclusion
criteria were that participants were medication free and presented with no
comorbidities. ECGs of control and eCAN were recorded and heart rate changes
analyzed with the fast Fourier transform (FFT) and Lomb-Scargle periodogram
(LSP). Ten-second to 5-minute recordings were extracted from a 15-minute lead-II
ECG and accuracy in assessment of eCAN determined. RESULTS: The eCAN group was
older ( P < .001) and systolic blood pressure was higher ( P < .01). HDL
cholesterol was also higher in the eCAN group ( P < .05). HRV analysis showed
that both FFT and LSP results were significantly different between eCAN and
control down to a 10-second ECG length for low frequency (LSP: P = .013, FFT: P =
.024) and high frequency (HF-LSP: P = .002, FFT: P = .002) power. eCAN assessment
was optimal down to 90-second recordings with a sensitivity of 100% and
specificity of 29.49%. CONCLUSION: HRV is suitable for clinical practice from ECG
recordings of more than 90 seconds with high accuracy and repeatability within a
session for each participant.
PMID- 28406036
TI - Participatory Assessment of Factors Influencing Nutrition and Livelihoods in
Rural Ethiopia: Implications for Measuring Impacts of Multisector Nutrition
Programs.
AB - Agricultural interventions more effectively improve nutrition when they are
adapted to local contexts and engage multiple sectors. However, evidence is
limited for how to design and measure the impacts of such interventions. We
piloted a participatory methodology to collect community feedback to inform the
design and selection of measures for a multisector nutrition intervention in
Ethiopia. Study participants were purposively recruited from 6 rural districts in
Tigray and the Southern Nations, Nationalities, and Peoples' regions. Qualitative
data were collected from 12 focus group discussions with smallholder farmers (men
and women) participating in a nutrition-sensitive agriculture intervention. The
Sustainable Livelihoods Approach (SLA) combined with an ecological systems model
informed the survey tool and analyses. Analyses revealed 3 key findings. First,
there were regional differences in how communities defined assets important for
nutrition. Second, when asked to prioritize which assets were most important,
communities selected every SLA capital category; however, the types of assets
within each category differed by region. Third, the most commonly reported
barriers to good nutrition were traditional feeding behaviors (eg, men eating
before women) and lack of nutrition knowledge. How households use assets to
enhance nutrition is influenced by diverse and dynamic cultural, social,
economic, and ecological factors. The participatory methods piloted in this study
present a novel approach to identify contextually relevant household, community,
and institutional assets used to support food and nutrition security.
PMID- 28406037
TI - Does acculturation affect the dietary intakes and body weight status of children
of immigrants in the U.S. and other developed countries? A systematic review.
AB - OBJECTIVE: This paper reviews available studies on the relationship between
acculturation and obesity among children of immigrants who have at least one
foreign-born parent. METHODS: A systematic review of relevant studies was
undertaken using PubMed, Web of Science, and PsychInfo. RESULTS: The initial
search identified 1317 potentially relevant publications, of which 21 were
retained after three rounds of screening. Most studies were conducted in the U.S.
The majority of studies used BMI or overweight/obesity prevalence as the outcome
variable, while two studies used dietary intake. Three studies used standardized
acculturation scales, while most of the studies used generation, duration of
residency in host country, and language as proxy measures of acculturation. The
relationship between acculturation and outcomes varied between the host countries
and origin countries for children of immigrants. CONCLUSION: This study suggests
children of immigrants with different cultural backgrounds may interact with host
countries to varying degrees, ultimately influencing their diet behaviours and
body weight status. Researchers are encouraged to adopt standardized
acculturation scales to compare the results across countries and populations.
PMID- 28406038
TI - The GALA study: relationship between galectin-3 serum levels and short- and long
term outcomes of patients with acute heart failure.
AB - OBJECTIVE: We tested the hypothesis that early measurement of galectin-3 at the
emergency department (ED) during an episode of acute heart failure (AHF) allows
predicting short- and long-term outcomes. METHODS: We performed an exploratory
study including 115 patients consecutively diagnosed with AHF in a single ED.
Clinical and analytical variables were recorded. The primary endpoint was 30-day
all-cause mortality, and secondary endpoints were 30-day composite outcome
(death, rehospitalization or ED reconsultation, whichever first) and 1-year
mortality. RESULTS: Seven patients (6.1%) died within 30 days and 43 (37.4%)
within 1 year. The 30-day composite endpoint was observed in 21.1% of patients.
Galectin-3 was correlated with NT-proBNP and the glomerular filtration rate but
not with age and s-cTnI. Measured at time of ED arrival, galectin-3 showed good
discriminatory capacity for 30-day mortality (AUC ROC: 0.732; 95% CI 0.512-0.953;
p = 0.041) but not for 1-year mortality (0.521; 0.408-0.633; p = 0.722). Patients
with galectin-3 concentrations >42 MUg/L had an OR = 7.67(95%CI = 1.57-37.53; p =
0.012) for 30-day mortality. Conversely, NT-proBNP only showed predictive
capacity for 1-year mortality (0.642; 0.537-0.748; p = 0.014). Patients with NT
proBNP concentrations >5400 ng/L had an OR = 4.34 (95%CI = 1.93-9.77; p < 0.001)
for 1-year mortality. These increased short- (galectin-3) and long-term (NT
proBNP) risks remained significant after adjustment for age or renal function. s
cTnI failed in both short- and long term death prediction. No biomarker predicted
the short-term composite endpoint. CONCLUSION: These results suggest that
galectin-3 could help to monitor the risk of short-term mortality in unselected
patients with AHF attended in the ED.
PMID- 28406039
TI - A Methodology to Compare Insulin Dosing Recommendations in Real-Life Settings.
AB - BACKGROUND: We propose a methodology to analyze complex real-life glucose data in
insulin pump users. METHODS: Patients with type 1 diabetes (T1D) on insulin pumps
were recruited from an academic endocrinology practice. Glucose data, insulin
bolus (IB) amounts, and self-reported alcohol consumption and exercise events
were collected for 30 days. Rules were developed to retrospectively compare IB
recommendations from the insulin pump bolus calculator (IPBC) against
recommendations from a proposed decision aid (PDA) and for assessing the PDA's
recommendation for exercise and alcohol. RESULTS: Data from 15 participants were
analyzed. When considering instances where glucose was below target, the PDA
recommended a smaller dose in 14%, but a larger dose in 13% and an equivalent IB
in 73%. For glucose levels at target, the PDA suggested an equivalent IB in 58%
compared to the subject's IPBC, but higher doses in 20% and lower in 22%. In
events where postprandial glucose was higher than target, the PDA suggested
higher doses in 25%, lower doses in 13%, and equivalent doses in 62%. In 64% of
all alcohol events the PDA would have provided appropriate advice. In 75% of
exercise events, the PDA appropriately advised an IB, a carbohydrate snack, or
neither. CONCLUSIONS: This study provides a methodology to systematically analyze
real-life data generated by insulin pumps and allowed a preliminary analysis of
the performance of the PDA for insulin dosing. Further testing of the
methodological approach in a broader diabetes population and prospective testing
of the PDA are needed.
PMID- 28406040
TI - Seven-Year Surveillance of the Clinical Performance of a Blood Glucose Test Strip
Product.
AB - BACKGROUND: A key approach in enabling people with diabetes to better manage
their condition is through self-monitoring of blood glucose (SMBG). Any
functional SMBG system should demonstrate clinical accuracy across a broad
glucose range and be insensitive to hematocrit. Furthermore, it should be
incumbent on the manufacturer to demonstrate that their product continues to meet
clinical accuracy claims during product lifetime. METHODS: Test strips from a
globally distributed SMBG product were sampled from randomly selected production
batches as part of the manufacturer's routine product evaluation process.
Clinical accuracy was assessed within diabetes patients at 3 clinic sites against
a standard reference method and evaluated against system accuracy in accordance
with the ISO 15197:2015 standard (unchanged from ISO 15197:2013 in terms of
performance specifications). Data were collected over 7 years (2010-2016) and
comprised 73,600 individual glucose results. Overall clinic performance was
assessed, as was accuracy at low and high glucose levels and extremes of
hematocrit. RESULTS: Across the 7-year surveillance period, overall test strip
clinical accuracy was 97.8% versus the 95% ISO-defined minimum criterion with by
year values of 97.0-98.6%. Accuracy at the lowest (<=50 mg/dL) and highest (>400
mg/dL) ranges of glucose was 97.0% and 98.3% respectively. Within these low/high
blood glucose subpopulations, accuracy at the lower and upper first percentile
hematocrit ranges, was 98.9%, and 97.1% respectively. CONCLUSIONS: This 7-year
surveillance program showed the test strips to have excellent clinical accuracy
at the outer ranges of subject blood glucose and hematocrit, based on assessment
against the ISO 15197:2015 clinical accuracy criterion.
PMID- 28406041
TI - The nexus between health and time use among racially and ethnically diverse
women.
AB - OBJECTIVES: Ethnic and racial health disparities have been well-documented in the
scholarly literature. In recent years, evidence about time spent in physical
(in)activity and its relationship to physical and mental health has also emerged.
This study assesses if observed ethnic/racial health differences were associated
with differences in time use. DESIGN: Our analyses utilized baseline data from
510 Utah women who enrolled in one of two community-based, participatory research
intervention studies between 2012 and 2015. The distinct racial/ethnic groups
included African immigrants, African Americans, Latinas, Native Hawaiians/Pacific
Islanders, American Indians/Alaskan Natives, and rural White, Non-Latina women.
In the baseline survey, respondents reported the typical time they spent in paid
employment, television/movie viewing, physical activity, food preparation/clean
up, and sleep. Cluster analysis was used to identify seven distinct patterns of
time use within these five activities. We related these time use patterns along
with race/ethnicity, socio-demographics, and other potentially contributing
health-related factors (e.g. smoking status) to two health outcomes: (1) self
reported health status, and (2) depression. RESULTS: Our time use clusters
revealed heterogeneity by racial/ethnic groups, suggesting that some of the
health effects that may have been previously ascribed to group membership should
instead be attributed to (un)healthy patterns of time use. In particular,
spending too much time in sedentary activities such as watching television/movies
and too little time sleeping both linked to poor physical and mental health,
independently of racial/ethnic group membership. CONCLUSIONS: Researchers and
policy makers designing culturally sensitive physical activity health-related
interventions should consider patterns of time use that are associated with poor
health. Programs designed to improve sleep time and reduce sedentary television
viewing time may be as important as interventions designed to increase physical
activity time. These broader patterns of time use mediated the relationships
between race/ethnicity and physical and mental health for the women in our study.
PMID- 28406042
TI - Attributes of nuclear imaging centers impacting physician referrals for single
photon emission computed tomography myocardial perfusion imaging tests.
AB - AIM: To evaluate nuclear imaging center attributes that cardiologists and primary
care physicians (PCPs) consider when referring patients for single-photon
emission computed tomography myocardial perfusion imaging (SPECT-MPI) tests, and
how these attributes impact physician referral decisions in the United States.
METHODS: A targeted literature review and seven one-to-one interviews with
physicians and imaging center directors were conducted to identify attributes
that could impact physicians' referral decisions. The impact of the identified
attributes was assessed via an online discrete choice survey among eligible PCPs
and cardiologists randomly selected from a nationally representative panel, and
quantified with an odds ratio (OR) scale estimated with a multivariable logistic
regression. RESULTS: Nine two-level attributes were identified: ease of the
referral process, waiting time for tests, insurance preauthorization assistance,
time to receive results, conclusive test reports, patient satisfaction, a
protocol for rapid conversion from an exercise to a pharmacological stress test,
patient communication, and assistance with parking/wheelchair access. A total of
410 physicians, including 208 (50.7%) cardiologists and 202 (49.3%) PCPs
completed the survey. Among all physicians, a protocol that allows for a rapid
conversion from an exercise to a pharmacological stress test (OR = 2.9) and
preauthorization assistance (OR = 2.6) were the most impactful attributes.
Additionally, cardiologists preferred imaging centers that provide an easy
referral process (OR = 2.7), while PCPs favored centers offering a conclusive
test report (OR = 2.4). LIMITATIONS: Some center features that might impact
physician referral decision were not evaluated in this study, if they were not
easily changeable from an imaging center's perspective. CONCLUSIONS: The
availability of a protocol for rapid conversion from an exercise to a
pharmacological stress test and preauthorization assistance had the most
significant impact on physician referral decisions for SPECT-MPI. Additionally,
cardiologists preferred centers providing an easy referral process, while PCPs
favored those offering a concluding statement and actionable steps in test
reports.
PMID- 28406043
TI - Cardioprotective effect of magnetic hydrogel nanocomposite loaded N,alpha-L
rhamnopyranosyl vincosamide isolated from Moringa oleifera leaves against
doxorubicin-induced cardiac toxicity in rats: in vitro and in vivo studies.
AB - Cardioprotective effect of N, alpha-L-rhamnopyranosyl vincosamide (VR), isolated
from the leaves of Moringa oleifera plant in doxorubicin (Dox)-induced cardiac
toxicity rats was evaluated. Twelve (12) rats were randomly selected into three
groups; two rats received distilled water in the control group, five rats in
group I received varying concentration of VR treatment, and group II containing
five rats received varying concentration of VR-loaded magnetic hydrogel
nanocomposite. Malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide
dismutase (SOD) enzymes activities level were analysed after two weeks. In
addition, the expression of three heart failure markers; beta major
histocompatibility complex (beta-MHC), atrial natriuretic peptide (ANP), and B
type natriuretic peptide (BNP) were also evaluated. It was observed that the
level of these markers expression decreases with an increase in VR concentration
(p < 0.05). The reduced GSH and SOD level were increased after VR administration,
this extract also reduced the initially increased MDA level in cardiac tissue.
Pharmacokinetic parameters evaluation showed that nanogel treated rats possesses
a significantly increased VR plasma concentration, Cmax, Kel, t1/2(a), t1/2(el),
Ka and AUC. The result of this study indicated that VR may help to lower the
dosage level, and reduces the treatment course in cardiovascular diseases (CVD).
Our conclusion proposes the cardio-protective ability of the isolated VR and its
beneficial effect via free radical scavenging properties.
PMID- 28406044
TI - Stage-specific mortality and survival trends of prostate cancer patients in
Finland before and after introduction of PSA.
AB - BACKGROUND: The early diagnosis and right treatment strategy of localized
prostate cancer (PCa) remains problematic. In order to characterize the survival
of PCa patients, we compared patients' all-cause and cancer-specific mortalities
between pre- and post-PSA periods by stage in Finland. MATERIAL AND METHODS: All
PCa cases diagnosed in Finland between 1985 and 2013 (N = 91,329) were identified
from the Finnish Cancer Registry (FCR). PCa stage at diagnosis was defined as
localized, local node positive or metastasized. Standardized mortality ratios
(SMRs), and relative and cause-specific survival were assessed by stage and
introduction of PSA testing. The main limitation was the high proportion of men
with unknown stage (28%). RESULTS: A clear decreasing trend in the SMR of PCa
patients was evident when pre- and post-PSA eras were compared: for localized
PCa, the SMR was 1.43 (95%CI 1.38-1.48) in 1985-1989 and 0.98 (95%CI 0.95-1.01)
in 2000-2004, and for metastasized PCa, the SMRs were 4.51 (95%CI 4.30-4.72) and
3.01 (95%CI 2.89-3.12), respectively. Difference between cause-specific and
relative survival was pronounced in localized PCa in post-PSA period: 10-year
relative survival was 94.6% (95%CI 91.4-97.8) and cause-specific 84.2% (95%CI
82.9-85.5%). In metastasized PCa the difference was not that significant.
CONCLUSIONS: From 1985 to 2009, the SMR among men diagnosed with PCa decreased
significantly in Finland. Among men with localized PCa, the SMR decreased even
below that of the Finnish male population. This and the increased difference
between relative and cause-specific survival reflects most likely selection of
men to opportunistic PSA testing. The results highlight the importance of caution
in the use of PSA testing in healthy men.
PMID- 28406045
TI - A methacrylic hyaluronic acid derivative for potential application in oral
treatment of celiac disease.
AB - OBJECTIVE: Aim of this work was the synthesis of a methacrylic hyaluronic acid
(HA) derivative and the production, via photocrosslinking, of related hydrogels
loaded with an endopeptidase intended for a potential oral treatment of celiac
disease. METHODS: The methacrylic derivative of HA was prepared through a one-pot
procedure involving the reaction with ethylenediamine (EDA) and methacrylic
anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare
photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from
Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained
hydrogels were recovered as gels or freeze-dried powders. RESULTS: Hydrogels
obtained as freeze-dried powders, are able to protect loaded enzyme from
degradation due to freeze-drying process and from alteration during storage,
overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA
hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in
sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as
demonstrated through in vitro studies on BALB 3T3 cells. CONCLUSIONS: Prepared
hydrogels show a potential application for oral treatment of celiac disease
thanks to the possibility to release enzymes able to detoxify the gliadin peptide
that induces the immunogenic response.
PMID- 28406046
TI - DEPDC5 as a potential therapeutic target for epilepsy.
AB - INTRODUCTION: Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein
5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1
(GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target
of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and
metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both
acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome
with epilepsy, however GATOR1 gene mutations have recently been shown to cause
lesional and non-lesional focal epilepsy. Areas covered: This review summarizes
the mTOR pathway, including regulators and downstream effectors, emphasizing
recent developments in the understanding of the complex role of the GATOR1
complex. We review the epilepsy types associated with mTOR overactivity,
including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy,
cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy.
Currently available mTOR inhibitors are discussed, primarily rapamycin analogs
and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive
therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely
be anti-epileptogenic and more selective than currently available mTOR
inhibitors. Therapeutic effects might be synergistic with certain existing
dietary therapies, including the ketogenic diet.
PMID- 28406047
TI - Radiological prizes awarded in 2016.
PMID- 28406048
TI - Placement of central venous port catheters and peripherally inserted central
catheters in the routine clinical setting of a radiology department: analysis of
costs and intervention duration learning curve.
AB - Background Placement of central venous port catheters (CVPS) and peripherally
inserted central catheters (PICC) is an integral component of state-of-the-art
patient care. In the era of increasing cost awareness, it is desirable to have
more information to comprehensively assess both procedures. Purpose To perform a
retrospective analysis of interventional radiologic implantation of CVPS and PICC
lines in a large patient population including a cost analysis of both methods as
well as an investigation the learning curve in terms of the interventions'
durations. Material and Methods All CVPS and PICC line related interventions
performed in an interventional radiology department during a three-year period
from January 2011 to December 2013 were examined. Documented patient data
included sex, venous access site, and indication for CVPS or PICC placement. A
cost analysis including intervention times was performed based on the prorated
costs of equipment use, staff costs, and expenditures for disposables. The
decrease in intervention duration in the course of time conformed to the learning
curve. Results In total, 2987 interventions were performed by 16 radiologists:
1777 CVPS and 791 PICC lines. An average implantation took 22.5 +/- 0.6 min
(CVPS) and 10.1 +/- 0.9 min (PICC lines). For CVPS, this average time was
achieved by seven radiologists newly learning the procedures after performing 20
CVPS implantations. Total costs per implantation were ?242 (CVPS) and ?201 (PICC
lines). Conclusion Interventional radiologic implantations of CVPS and PICC lines
are well-established procedures, easy to learn by residents, and can be implanted
at low costs.
PMID- 28406049
TI - Evaluation of reduced-dose CT for acute non-traumatic abdominal pain: evaluation
of diagnostic accuracy in comparison to standard-dose CT.
AB - Background Patients with acute non-traumatic abdominal pain often undergo
abdominal computed tomography (CT). However, abdominal CT is associated with high
radiation exposure. Purpose To evaluate diagnostic performance of a reduced-dose
100 kVp CT protocol with advanced modeled iterative reconstruction as compared to
a linearly blended 120 kVp protocol for assessment of acute, non-traumatic
abdominal pain. Material and Methods Two radiologists assessed 100 kVp and
linearly blended 120 kVp series of 112 consecutive patients with acute non
traumatic pain (onset < 48 h) regarding image quality, noise, and artifacts on a
five-point Likert scale. Both radiologists assessed both series for abdominal
pathologies and for diagnostic confidence. Both 100 kVp and linearly blended 120
kVp series were quantitatively evaluated regarding radiation dose and image
noise. Comparative statistics and diagnostic accuracy was calculated using
receiver operating curve (ROC) statistics, with final clinical diagnosis/clinical
follow-up as reference standard. Results Image quality was high for both series
without detectable significant differences ( P = 0.157). Image noise and
artifacts were rated low for both series but significantly higher for 100 kVp ( P
<= 0.021). Diagnostic accuracy was high for both series (120 kVp: area under the
curve [AUC] = 0.950, sensitivity = 0.958, specificity = 0.941; 100 kVp: AUC >=
0.910, sensitivity >= 0.937, specificity = 0.882; P >= 0.516) with almost perfect
inter-rater agreement (Kappa = 0.939). Diagnostic confidence was high for both
dose levels without significant differences (100 kVp 5, range 4-5; 120 kVp 5,
range 3-5; P = 0.134). The 100 kVp series yielded 26.1% lower radiation dose
compared with the 120 kVp series (5.72 +/- 2.23 mSv versus 7.75 +/- 3.02 mSv, P <
0.001). Image noise was significantly higher in reduced-dose CT (13.3 +/- 2.4 HU
versus 10.6 +/- 2.1 HU; P < 0.001). Conclusion Reduced-dose abdominal CT using
100 kVp yields excellent image quality and high diagnostic accuracy for the
assessment of acute non-traumatic abdominal pain.
PMID- 28406050
TI - Investigation of pyrrolizidine alkaloids including their respective N-oxides in
selected food products available in Hong Kong by liquid chromatography
electrospray ionisation mass spectrometry.
AB - This study determined the levels of pyrrolizidine alkaloids (PAs), including
their respective N-oxides, in foodstuffs available in Hong Kong by liquid
chromatography-electrospray ionisation tandem mass spectrometry. A total of 234
samples (48 food items) were collected randomly from a local market and analysed.
About 50% of samples were found to contain detectable amount of PAs. Amongst the
48 food items, PAs were not detected in 11 food items, including barley flour,
beef, cattle liver, pork, pig liver, chicken meat, chicken liver, milk, non
fermented tea, Melissa tea and linden tea. For those found to contain detectable
PAs, the summed PA content ranged up to 11,000 ug kg-1. The highest sum of PA
content among the 37 food items calculated with lower bound was cumin seed, then
followed by oregano, tarragon and herbs de Provence with ranges of 2.5-11,000,
1.5-5100, 8.0-3300 and 18-1300 ug kg-1 respectively. Among the samples, the
highest sum of PA content was detected in a cumin seed sample (11,000 ug kg-1),
followed by an oregano (5100 ug kg-1), a tarragon (3300 ug kg-1) and a herbs de
Provence (1300 ug kg-1). In general, the results of this study agreed well with
other published results in peer-reviewed journals, except that the total PAs in
honey and specific tea infusion in this study were comparatively lower.
PMID- 28406051
TI - Antidepressant-like deliverables from the sea: evidence on the efficacy of three
different brown seaweeds via involvement of monoaminergic system.
AB - Brown seaweeds exhibit several health benefits in treating and managing wide
array of ailments. In this study, the antidepressant-like effect of methaolic
extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and
Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats.
Oral administration of SS, SM, and NZ extract (30-60 mg/kg) exhibited
antidepressant-like activity in FST by reducing immobility time as compared to
control group, without inducing significant change in ambulatory behavior in open
field test. In order to evaluate the involvement of monoaminergic system, rats
were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin
(PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and
propranolol) antagonists. Rats receiving treatment for 28 days were decapitated
and brains were analyzed for monoamine levels. It may be concluded that the
extracts of SS, SM, and NZ produces antidepressant-like activity via modulation
of brain monoaminergic system in a rat model.
PMID- 28406052
TI - The psychometric properties of the Perceived Stress Scale-10 among patients with
systemic lupus erythematosus.
AB - Objective Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune
disease characterized by periods of remission and recurrent flares, which have
been associated with stress. Despite the significance of stress in this disease,
the Perceived Stress Scale-10 has yet to be psychometrically evaluated in
patients with SLE. Methods Exploratory factor analysis was used to examine the
structural validity of the Perceived Stress Scale-10 among patients with SLE ( N
= 138) receiving medical care at Cedars Sinai Medical Center. Cronbach's
coefficient alpha was used to examine internal consistency reliability, and
Pearson product-moment correlations were used to examine convergent validity with
measures of anxiety, depression, helplessness, and disease activity. Results
Exploratory factor analysis provided support for a two-factor structure
(comparative fit index = .95; standardized root mean residual = .04; root mean
square error of approximation = .08). Internal consistency reliability was good
for both factors (alpha = .84 and .86). Convergent validity was evidenced via
significant correlations with measures of anxiety, depression, and helplessness.
There were no significant correlations with the measure of disease activity.
Conclusion The Perceived Stress Scale-10 can be used to examine perceived stress
among patients with SLE.
PMID- 28406053
TI - Burden of illness in systemic lupus erythematosus: results from a UK patient and
carer online survey.
AB - Objective The objective of this study was to assess the impact of systemic lupus
erythematosus (SLE) on patients and carers. Methods Adults with SLE and carers of
SLE patients completed a UK-specific online survey covering many aspects of the
disease. Surveys were developed in collaboration with an NHS lupus unit and a
lupus patient organization. Results A total of 121 patients and 31 carers
completed the surveys. Of the 70% of patients initially misdiagnosed with another
condition, 59% received treatment for the misdiagnosis. Fatigue was the most
debilitating symptom, experienced daily by 79% of patients. The proportion of
patients not reporting flares to healthcare providers varied with flare severity:
mild flares (43%), moderate flares (15%) and severe flares (5%). Most patients
(89%) reported reduced ability to socialize, and 76% had changed employment; of
these, 52% stopped working completely. Over one-half (52%) of carers in paid
employment missed time from work, and 55% of carers reported a worsened financial
status. Most carers (87%) experienced interference with social activities.
Conclusion SLE is commonly misdiagnosed and has a considerable impact on the
physical, social and financial status of patients and carers. Increased awareness
of the disease among healthcare providers and employers of patients and their
carers is needed.
PMID- 28406054
TI - Decitabine as salvage therapy for primary induction failure of acute myeloid
leukemia.
PMID- 28406055
TI - Graph Theory and Brain Connectivity in Alzheimer's Disease.
AB - This article presents a review of recent advances in neuroscience research in the
specific area of brain connectivity as a potential biomarker of Alzheimer's
disease with a focus on the application of graph theory. The review will begin
with a brief overview of connectivity and graph theory. Then resent advances in
connectivity as a biomarker for Alzheimer's disease will be presented and
analyzed.
PMID- 28406056
TI - Comparison of adsorption equilibrium models and error functions for the study of
sulfate removal by calcium hydroxyapatite microfibrillated cellulose composite.
AB - In the present study, the adsorption of sulfates of sodium sulfate (Na2SO4) and
sodium lauryl sulfate (SLS) by calcium hydroxyapatite-modified microfibrillated
cellulose was studied in the aqueous solution. The adsorbent was characterized
using elemental analysis, Fourier transform infrared, scanning electron
microscope and elemental analysis in order to gain the information on its
structure and physico-chemical properties. The adsorption studies were conducted
in batch mode. The effects of solution pH, contact time, the initial
concentration of sulfate and the effect of competing anions were studied on the
performance of synthesized adsorbent for sulfate removal. Adsorption kinetics
indicated very fast adsorption rate for sulfate of both sources (Na2SO4 and SLS)
and the adsorption process was well described by the pseudo-second-order kinetic
model. Experimental maximum adsorption capacities were found to be 34.53 mg g-1
for sulfates of SLS and 7.35 mg g-1 for sulfates of Na2SO4. The equilibrium data
were described by the Langmuir, Sips, Freundlich, Toth and Redlich-Peterson
isotherm models using five different error functions.
PMID- 28406057
TI - Subclinical hypothyroidism: Should we treat?
AB - Subclinical hypothyroidism (also known as compensated hypothyroidism or mild
hypothyroidism) is a condition associated with a raised serum concentration of
thyroid stimulating hormone (TSH) but a normal serum free thyroxine (FT4). It is
common, affecting about 10% of women above the age of 55 years. Autoimmunity is
the commonest cause of subclinical hypothyroidism. About 2.5% of patients with
subclinical hypothyroidism progress to clinically overt hypothyroidism each year;
the rate of progression is higher in patients with thyroid autoantibodies and
higher thyroid stimulating hormone levels. However, thyroid function normalises
spontaneously in up to 40% cases. Only a small minority of patients with
subclinical hypothyroidism have symptoms, and the evidence to support that
levothyroxine ameliorate the symptoms in these patients is weak. Subclinical
hypothyroidism in younger patients (<65 years) is associated with an increased
risk of coronary heart disease, heart failure and cerebrovascular disease. The
risk increases with increasing levels of thyroid stimulating hormone, and is
particularly high in patients with TSH levels >=10.0 mu/L. There is lack of
evidence from randomised controlled trials as to whether levothyroxine treatment
can prevent these risks, although a large observational study of the UK general
practice research database has shown that levothyroxine may reduce the risk of
coronary heart disease in younger patients (<70 years). Therefore, the decision
whether to treat or not to treat subclinical hypothyroidism should be made after
careful consideration of the patient's age, the presence of symptoms, the
presence of thyroid antibodies and other risk factors such as cardiovascular
disease.
PMID- 28406058
TI - The Migrant Border Crossing Study: A methodological overview of research along
the Sonora-Arizona border.
AB - Increased border enforcement efforts have redistributed unauthorized Mexican
migration to the United States (US) away from traditional points of crossing,
such as San Diego and El Paso, and into more remote areas along the US-Mexico
border, including southern Arizona. Yet relatively little quantitative scholarly
work exists examining Mexican migrants' crossing, apprehension, and repatriation
experiences in southern Arizona. We contend that if scholars truly want to
understand the experiences of unauthorized migrants in transit, such migrants
should be interviewed either at the border after being removed from the US, or
during their trajectories across the border, or both. This paper provides a
methodological overview of the Migrant Border Crossing Study (MBCS), a unique
data source on Mexican migrants who attempted an unauthorized crossing along the
Sonora-Arizona border, were apprehended, and repatriated to Nogales, Sonora in
2007-09. We also discuss substantive and theoretical contributions of the MBCS.
PMID- 28406059
TI - Investigating the ion dependence of the first unfolding step of GTPase
Associating Center ribosomal RNA.
AB - The interactions in the tertiary structure of a ribosomal RNA fragment in the
GTPase Associating Center (GAC) have been experimentally studied, but the roles
of the bound and diffuse cations in its folding pathway have not yet been fully
elucidated. Melting experiments have shown that the temperature of the first of
the two distinguishable transitions in the unfolding pathway of the GAC RNA can
be regulated by altering the magnesium concentration, yet the physical
interpretation of such ion-dependent effects on folding have not been clearly
understood in spite of the availability of crystal structures that depict many
GAC RNA-ion interactions. Here, we use umbrella sampling and molecular dynamics
(MD) simulations to provide a physical description for the first transition in
this unfolding pathway, with a focus on the role of a chelated magnesium ion. Our
results indicate that the presence of cations mediating the local interaction of
two loops stabilizes the folded state relative to the unfolded or partially
folded states. Also, our findings suggest that a bridging magnesium ion between
the two loops improves the stabilizing effect. This is consistent with the
multistep unfolding pathway proposed for the GAC RNA and highlights the
importance of ions in the first unfolding step. The results suggest how MD
simulations can provide insight into RNA unfolding pathways as a complementary
approach to experiments.
PMID- 28406060
TI - Auxin signaling through SCFTIR1/AFBs mediates feedback regulation of IAA
biosynthesis.
AB - We previously reported that exogenous application of auxin to Arabidopsis
seedlings resulted in downregulation of indole-3-acetic acid (IAA) biosynthesis
genes in a feedback manner. In this study, we investigated the involvement of the
SCFTIR1/AFB-mediated signaling pathway in feedback regulation of the indole-3
pyruvic acid-mediated auxin biosynthesis pathway in Arabidopsis. Application of
PEO-IAA, an inhibitor of the IAA signal transduction pathway, to wild-type
seedlings resulted in increased endogenous IAA levels in roots. Endogenous IAA
levels in the auxin-signaling mutants axr2-1, axr3-3, and tir1-1afb1-1afb2-1afb3
1 also increased. Furthermore, YUCCA (YUC) gene expression was repressed in
response to auxin treatment, and expression of YUC7 and YUC8 increased in
response to PEO-IAA treatment. YUC genes were also induced in auxin-signaling
mutants but repressed in TIR1-overexpression lines. These observations suggest
that the endogenous IAA levels are regulated by auxin biosynthesis in a feedback
manner, and the Aux/IAA and SCFTIR1/AFB-mediated auxin-signaling pathway
regulates the expression of YUC genes.
PMID- 28406061
TI - Effect of packing material on organic matter removal efficiency in an anaerobic
aerobic baffled bioreactor.
AB - The aim of the present work was to study the effect of packing material on the
organic matter removal efficiency (OMRE) in an anaerobic-aerobic baffled
bioreactor (AAB). For this purpose, two different experiments were conducted with
two types of packing material: activated carbon (AC) particles and polyurethane
foam (PF). The system consisted of two treatments; the first one was anaerobic,
where hydrolysis, acetogenesis and methanogenesis took place. In anaerobic
chambers, there were no packing materials and the operating conditions were the
same in both experiments. The second treatment was aerobic and both materials
were placed at different times as a bedding. The parameters measured were
chemical oxygen demand (COD), dissolved chemical oxygen demand (CODd), total
organic carbon (TOC), nitrate concentration (NO3-), ammonium concentration
(NH4+), electric conductivity (sigma), alkalinity (Alky) and hydrogen potential
(pH). Paired t-Student test showed that there was no significant difference in
the OMRE in anaerobic treatment, whereas there was in aerobic treatment, due to
the effect of packing material. NH4+ and NO3- showed a negative Pearson
correlation in both experiments, indicating the presence of the nitrification
process in the aerobic chamber. AAB packed with PF had better performance at
obtaining an OMRE of around 63%, whereas AAB packed with AC presented an OMRE of
around 51%.
PMID- 28406062
TI - Constraint approaches to the estimation of relative risk.
AB - In medical and epidemiologic studies, relative risk is usually the parameter of
interest. However, calculating relative risk using standard log-Binomial
regression approach often encounters non-convergence. A modified Poisson
regression, which uses robust variance, was proposed by Zou in 2004. Although the
modified Poisson regression with sandwich variance estimator is valid for the
estimation of relative risk, the predicted probability of the outcome may be
greater than the natural boundary 1 for the unobserved but plausible covariate
combinations. Moreover, the lower and upper bounds of confidence intervals for
predicted probabilities could fall out of (0, 1). Chu and Cole, in 2010, proposed
a Bayesian approach to overcome this issue. Posterior median was used to get the
parameter estimation. However, the Bayesian approach may provide biased
estimation, especially when the probability of outcome is high. In this article,
we propose an alternative constraint optimization approach for estimating
relative risk. Our approach can reach similar or better performance than Bayesian
approach in terms of bias, root mean square error, coverage rate, and predictive
probabilities. Simulation studies are conducted to demonstrate the usefulness of
this approach. Our method is also illustrated by Prospective Registry Evaluating
Myocardial Infarction: Event and Recovery data.
PMID- 28406063
TI - Metabolites predict lesion formation and severity in relapsing-remitting multiple
sclerosis.
AB - BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which
are visualized with conventional T2-weighted magnetic resonance imaging (MRI).
Little is known about local metabolic processes preceding the appearance and
during the pathological development of new lesions. OBJECTIVE: To identify
metabolite changes preceding white matter (WM) lesions and pathological severity
of lesions over time. METHODS: A total of 59 relapsing-remitting multiple
sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging
included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion
tensor imaging (DTI). RESULTS: A total of 16 new lesions appeared within the MRSI
slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6
months before new lesions appeared. In these areas, the increase in creatine and
choline 6 months before until lesion appearance was negatively correlated with
radial diffusivity (rho = -0.73, p = 0.002 and rho = -0.72, p = 0.002). Increase
in creatine also correlated with the increase of axial diffusivity in the same
period (rho = -0.53, p = 0.034). When splitting the lesions into "mild" and
"severe" based on radial diffusivity, only mild lesions showed an increase in
creatine and choline during lesion formation ( p = 0.039 and p = 0.008,
respectively). CONCLUSION: Increased glutamate heralded the appearance of new T2
visible WM lesions. In pathologically "mild" lesions, an increase in creatine and
choline was found during lesion formation.
PMID- 28406064
TI - Optimization of the balance between effort and yield in unilateral surgical
transfer of mouse embryos.
AB - Surgical transfer of embryos is carried out daily in animal facilities worldwide
for the rederivation of mouse strains/lines, among other purposes. Current
protocols described in laboratory manuals recommend using a high number of
embryos during transfer, typically in the range of 15 up to 25. To optimize the
use of resources it is necessary to estimate and relate the effort required and
the yield obtained. Here, we analyse the balance between the number of embryos
transferred (the effort), and the yield as the number of born pups obtained from
surgical embryo transfer. To accomplish this, we have analyzed data obtained
during rederivation of nearly one hundred lines of mice to a new animal facility.
Our results confirm that the use of increasing numbers of embryos per transfer
increases the yields of born pups, as has been described previously in the
literature, but they also highlight the disproportionate effort required, i.e. in
the number of embryos that needed to be transferred. An estimate of the mean
expected yields of surgical transfers and their comparison with the actual
observed yields indicated that the balance between effort and yield is optimized
when using lower numbers of embryos than in currently used protocols, in the
range of 8 to 12. Given the heterogeneous nature of the data presented and
analyzed here, which is from a population of mice that may be considered as
representative of any animal facility, our optimization approach should help save
resources in similar facilities and improve the yields of embryo transfer
procedures.
PMID- 28406065
TI - Erratum.
PMID- 28406066
TI - Telemedicine consultation for patients with diabetes mellitus: a cluster
randomised controlled trial.
AB - Introduction There is a widening discrepancy between the increasing number of
patients with diabetes mellitus and the health care resources available to manage
these patients. Telemedicine has been used in a number of instances to improve
and deliver health care where traditional care delivery methods may encounter
difficulty. We conducted a cluster randomised controlled trial of telemedicine
consultation to manage patients with diabetes mellitus. Methods Eleven primary
care centres attached to one Veteran Administration tertiary care centre were
randomised to provide patients with diabetes consultation referral either by
usual consultation in diabetes clinic or telemedicine consultations via
videoconference. Results Altogether, 199 patients were managed by telemedicine
consultation and 83 by usual consultation. Patients in both groups showed a small
decrease in haemoglobin A1c, with no statistical difference between the groups
(telemedicine consultation -1.01% vs usual consultation -0.68%, p = 0.19).
Surveys of patients and semi-structured interviews with primary care providers
showed better response and satisfaction with telemedicine consultations.
Discussion This study shows similar clinical outcomes as measured by glycaemic
control for patients with diabetes mellitus having a specialist consultation
using real-time telemedicine consultation as compared to in-clinic consultation.
Telemedicine consultation was also associated with better patient and primary
care provider satisfaction.
PMID- 28406067
TI - RNA and a cell wall component of Enterococcus faecalis IC-1 are required for
phagocytosis and interleukin 12 production by the mouse macrophage cell line
J774.1.
AB - Enterococcus faecalis is a resident lactic acid bacterium in the human intestine.
Its immunostimulatory action was reported to be enhanced by heat sterilization.
To investigate its beneficial actions, we evaluated the ability of 10 E. faecalis
strains to induce interleukin-12 (IL-12) production in a mouse macrophage cell
line, J774.1 and found that the strain, E. faecalis IC-1, had a potent IL-12
inducing ability. Furthermore, we investigated the underlying mechanism by
treating IC-1 cells with RNase or lysozyme. Its activity almost disappeared and
an antagonist of Toll-like receptor (TLR) 7 inhibited this activity. Moreover,
lysozyme-treated IC-1 bacteria were not phagocytized by J774.1 cells, and did not
induce IL-12 production. Based on our results, we propose that macrophages
recognize the cell wall components of IC-1, leading to phagocytosis. The IC-1 RNA
is then recognized by TLR7, which induces the production of IL-12.
PMID- 28406068
TI - Clinical and hematological relevance of JAK2 V617F and CALR mutations in BCR-ABL
negative ET patients.
AB - BACKGROUND: Classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs)
including polycythemia vera, essential thrombocythemia (ET), and primary
myelofibrosis frequently harbor JAK2, MPL, and CALR somatic mutations. METHODS:
AS-PCR for JAK2 V617F, pyrosequencing for MPL W515L/K, and PCR-fragment analysis
for CALR exon 9 mutations were established to analyze genomic DNA isolated from
peripheral blood samples of 58 newly diagnosed ET patients in Thailand. RESULTS:
JAK2 V617F was detected in 41 patients (71%) and CALR exon 9 mutation was
positive in eight patients (14%), whereas no mutation of MPL W515L/K was observed
in this study. Patients with CALR mutation were older (p = 0.023) and exhibited
lower number of platelet count (p = 0.041) than patients without CALR mutation.
Two previously known CALR mutation types were identified in this study (six
patients with CALR-type 1 and two patients with CALR-type 2). Additionally, no co
existence of JAK2 V617F and CALR mutations was identified in this work.
CONCLUSION: We reported the frequency of JAK2 V617F, MPL W515L/K, and CALR
mutations in Thai patients with ET. Clinical and hematological phenotypes of
patients were associated with JAK2 and CALR mutation statuses. The combination of
laboratory testing for the detection of JAK2, CALR, and MPL mutations is
necessary to improve the diagnosis and classification of BCR-ABL1-negative MPN.
PMID- 28406069
TI - Strain improvement of Lentzea sp. 7887 for higher yield per unit volume on
hydroxylation of cyclosporine derivative FR901459.
AB - A Gram-positive bacterium Lentzea sp. 7887 hydroxylates a cyclosporine derivative
FR901459 into AS1837812 (9-hydroxide), which is an important intermediate of
candidate drugs that target the hepatitis C virus. We screened a UV-induced
mutant, named M-1, which showed about 1.2-fold higher conversion yields, 2-fold
higher substrate concentrations (3.69 mM), and 2.5-fold higher yield per unit
volume than the wild-type strain.
PMID- 28406070
TI - An investigation of the relationship between autonomic dysreflexia and
intrathecal baclofen in patients with spinal cord injury.
AB - OBJECTIVE: To study the relationship between autonomic dysreflexia and
intrathecal baclofen in patients with spinal cord injury. DESIGN: Retrospective
chart review. SETTING: Inpatient and outpatient acute rehabilitation facility.
PARTICIPANTS: Thirty-four subjects. INTERVENTIONS: We reviewed patients' medical
records to ascertain the presence of symptomatic autonomic dysreflexia (AD) prior
to and after implantation of an intrathecal baclofen (ITB) pump for spasticity in
spinal cord injury patients. We recorded risk factors for autonomic dysreflexia
including kidney and bladder stones, heterotopic ossification (HO), and ischial /
sacral pressure ulcers. OUTCOME MEASURES: Presence of autonomic dysreflexia pre
and post-intrathecal baclofen pump placement, presence of risk factors associated
with autonomic dysreflexia including (1) kidney or bladder stones, (2)
heterotopic ossification, and (3) pressure ulcers. RESULTS: Of the 34 subjects,
25 (73.5%) experienced AD prior to ITB pump placement and only 2 (5.9%) after
placement. Four subjects (11.8%) had kidney or bladder stones, of which, all had
AD prior to placement and none had AD afterwards. Twenty-six subjects (76.5%) had
pressure ulcers, of which, all experienced AD prior to placement and only one
(0.02%) afterwards. Six patients (17.6%) had HO, of which 5 (83%) had AD prior to
placement and none afterwards. Additionally, three patients (8.8%) had at least 2
of the above risk factors, of which, all had AD prior to ITB placement and none
afterwards. CONCLUSION: This study showed a significant reduction of symptomatic
episodes of autonomic dysreflexia after spinal cord injury, even in those with
additional risk factors for development of autonomic dysreflexia.
PMID- 28406071
TI - Validation and reliability of the Spanish version of the Function in Sitting Test
(S-FIST) to assess sitting balance in subacute post-stroke adult patients.
AB - BACKGROUND: Function in Sitting Test (FIST) is a clinical functional assessment
of sitting balance validated in adults with stroke. For a major use of this, the
test is recommended to be translated in Spanish-speaking countries. OBJECTIVES:
Translate to Spanish the FIST and determine its intra-rater and inter-rater
reliabilities and concurrent validity as a measure of sitting balance in adult
individuals with stroke. METHODS: The original version was translated into
Spanish and was agreed by a team of experts. A back-translation into English was
subsequently performed and sent to the original author, who approved this version
named from now Spanish version of Function in Sitting Test (S-FIST). Sixty post
stroke patients' performance was recorded on a videotape. These videos were then
used to carry out four measurements to assess the intra-rater and inter-rater
reliabilities; two of these were performed by the same rater and the third and
fourth by a second and third rater. RESULTS: The S-FIST meets the following
requirements: good construct validity and high correlation with Spanish version
of Trunk Impairment Scale 2.0 (S-TIS 2.0) scores (r = 0.791) Spearman's rank,
high internal consistency (Cronbach's alpha-coefficient = 0.97), and high intra
rater and inter-rater reliabilities for the summed scores assessed by intra-class
correlation coefficient were 0.999 and 0.997, respectively. CONCLUSIONS: The S
FIST is valid and reliable and can be recommended for use in the evaluation of
dynamic and sitting balance and trunk control in future research and clinical
practice on post-stroke patients. Guidelines for treatment and level of quality
of trunk activity can be derived from its use.
PMID- 28406072
TI - Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism
and lamellar body biogenesis in A549 human alveolar epithelial cells.
AB - The pulmonary delivery of nanoparticles (NPs) is a promising approach in
nanomedicine. For the efficient and safe use of inhalable NPs, understanding of
NP interference with lung surfactant metabolism is needed. Lung surfactant is
predominantly a phospholipid substance, synthesized in alveolar type II cells
(ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro
and in vivo studies have reported NPs impact on surfactant homeostasis, but this
phenomenon has not yet been sufficiently examined. We showed that in ATII-like
A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs
(SiO2-SPIONs), which have a high potential in medicine, caused an increased
cellular amount of acid organelles and phospholipids. In SiO2-SPION treated
cells, we observed elevated cellular quantity of multivesicular bodies (MVBs),
organelles involved in LB biogenesis. In spite of the results indicating
increased surfactant production, the cellular quantity of LBs was surprisingly
diminished and the majority of the remaining LBs were filled with SiO2-SPIONs.
Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and
obviously destined for degradation. We also observed time- and dose-dependent
changes in mRNA expression for proteins involved in lipid metabolism. Our results
demonstrate that non-cytotoxic concentrations of SiO2-SPIONs interfere with
surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce
hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery,
we propose that potential NP interference with LB biogenesis is obligatorily
taken into account.
PMID- 28406073
TI - Rapid multiresidue determination of pesticides in livestock muscle and liver
tissue via modified QuEChERS sample preparation and LC-MS/MS.
AB - Many multiresidue methods for the determination of pesticides in vegetables and
fruits have been reported to date. However, few such methods have been employed
to investigate pesticide residues in animal tissue. In this study, an LC-MS/MS
multiresidue method coupled with modified QuEChERS extraction was developed and
validated for the investigation of eight pesticide residues: prallethrin (PR),
resmethrin (RMT), imidacloprid (IMC), diflubenzuron (DFB), cyromazine (CYR),
etofenprox (EFP), dinotefuran (DNT) and phthalthrin (PTLT). This method involves
initial extraction in a water/acetone system, the addition of salts and a
subsequent extraction/partitioning step and, finally, a clean-up step utilising
dispersive solid-phase extraction (SPE). The mean recoveries of seven of the
pesticides (the exception being CYR) ranged between 74.7% and 113.5%, and the CVs
of the livestock tissue - bovine, swine, and chicken muscle and liver tissue
spiked at 10 ng g-1 (50 ng g-1 for RMT and DNT) and 100 ng g-1 - were < 13.8%.
The recoveries of CYR in all muscle and liver spiked samples ranged from 56.9% to
78.3%, while those of RMT in swine liver were > 120%. Therefore, this method was
considered as being unsuitable for the investigation of these samples. The limits
of quantitation (LOQs) of seven of the investigated pesticides (the exception
being swine liver) in the tissue samples ranged from 0.9 to 15.2 ng g-1. We
therefore concluded that this LC-MS/MS multiresidue method is a valid and
suitable for the investigation of seven pesticides in animal tissue, but it is
unsuitable for the analysis of CYR in all animal tissues and RMT in swine liver
tissue.
PMID- 28406074
TI - EDITORIAL: Old Drugs * New Perspectives/New Compounds * Old Necessities: Focusing
on Combating Microbial Resistance - Part II.
PMID- 28406075
TI - Editorial (Thematic Issue: Hybrid Compounds as Multitarget Agents in Medicinal
Chemistry - Part II).
PMID- 28406076
TI - Corrigendum to The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other
Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in
Angiogenesis.
AB - In the Original Research Article entitled "The Competence of 7, 8-Diacetoxy-4
methylcoumarin and other Polyphenolic Acetates in Mitigating the Oxidative Stress
and their Role in Angiogenesis" Published in Current Topics in Medicinal
Chemistry, 2015, Vol. 15, No. 2, on page no. 179, the order of author names was
rearranged because second authorship is acceptable as they only acknowledge the
first and the second authorship as per the new policies of Medical Council of
India. The order of authors should be read as follows: Rini Joshi, Vishwajeet
Rohil, Shvetambri Arora, Sushma Manral, Ajit Kumar, Sanjay Goel, Nivedita Priya,
Prabhjoth Singh, Prija Ponnan, Suvro Chatterji, Bilikere S. Dwarakanath, Daman
Saluja, Diwan S. Rawat, Ashok K. Prasad, Luciano Saso, Ekta Kohli, Anthony L.
DePass, Marc E. Bracke, Virinder S. Parmar and Hanumantharao G. Raj.
PMID- 28406077
TI - EDITORIAL: Old Drugs * New Perspectives/New Compounds * Old Necessities: Focusing
on Combating Microbial Resistance - Part I.
PMID- 28406078
TI - Editorial: Hybrid Compounds as Multitarget Agents in Medicinal Chemistry - Part
I.
PMID- 28406079
TI - Distribution of energy intake throughout the day and weight gain: a population
based cohort study in Spain - CORRIGENDUM.
PMID- 28406081
TI - Ammonium Removal from Synthetic Stormwater using Clinoptilolite and
Hydroaluminosilicate Columns.
AB - Ammonium can enter stormwater control measures (SCMs) with the influent, but is
also the intermediate product between organic nitrogen and nitrate, and it is
important to retain and treat ammonium within the SCM. In this study the use of
aluminosilicate aggregates (CA) and clinoptilolite zeolite (ZT) was investigated
under SCM (column) conditions. ZT was found to have the highest capacity (0.45 mg
-N/g ZT vis-a-vis 0.33 mg -N/g CA)
at 2.5 mg NH4-N/L. The presence of Ca2+ and K+ was found to reduce the capacity
of the media significantly. Increasing the contact time from 10 minutes to 47
minutes enhanced the removal efficiency of the system by 70% for CA and 23% for
ZT, respectively. Finally, changes in the influent ammonium concentration
resulted in successful removal during concentration increases, but desorption of
ammonium for sudden concentration reduction. The use of ZT in media-based SCMs is
recommended for ammonium removal.
PMID- 28406080
TI - Genome amplification and promoter mutation expand the range of csgD-dependent
biofilm responses in an STEC population.
AB - Expression of the major biofilm components of E. coli, curli fimbriae and
cellulose, requires the CsgD transcription factor. A complex regulatory network
allows environmental control of csgD transcription and biofilm formation.
However, most clinical serotype O157 : H7 strains contain prophage insertions in
the csgD regulator, mlrA, or mutations in other regulators that restrict csgD
expression. These barriers can be circumvented by certain compensating mutations
that restore higher csgD expression. One mechanism is via csgD promoter mutations
that switch sigma factor utilization. Biofilm-forming variants utilizing RpoD
rather than RpoS have been identified in glycerol freezer stocks of the non
biofilm-forming food-borne outbreak strain, ATCC 43894. In this study we used
whole genome sequencing and RNA-seq to study genotypic and transcriptomic
differences between those strains. In addition to defining the consequences of
the csgD promoter switch and identifying new csgD-controlled genes, we discovered
a region of genome amplification in our laboratory stock of 43894 (designated
43894OW) that contributed to the regulation of csgD-dependent properties.
PMID- 28406082
TI - Intraventricular ganglioglioma with extensive hemorrhage.
AB - Gangliogliomas represent a rare form of neuroepithelial tumor (up to 1.3% of
brain tumors [1]), which even more rarely present with
hemorrhage or localize intraventricularly. To date, only two cases of
ganglioglioma with both of these features have been reported. Our patient is a 23
year-old woman who presented with signs and symptoms of increased intracranial
pressure (ICPI), with a post-subtotal resection diagnosis of WHO Grade I
ganglioglioma localizing bilaterally to the lateral ventricles. One year
following the operation, the tumor showed radiologic evidence of interval
hemorrhage, which was verified histopathologically following a second subtotal
resection. Greater than 95% of the lesion represented a large hematoma with
organization and well-defined fibrous pseudo-capsule, with very scanty fragments
of adjacent/peripheral low-grade neuroglial tumor. This case represents a very
rare presentation of intraventricular ganglioglioma with extensive hemorrhage.?.
PMID- 28406083
TI - Ambulatory arterial stiffness index, blood pressure variability, and nocturnal
blood pressure dip in children with IgA and Henoch-Schonlein nephropathy?.
AB - AIM: Evaluation of mean blood pressure values, ambulatory arterial stiffness
index (AASI), pulse pressure (PP), blood pressure variability (BPV), and
circadian blood pressure rhythm using ambulatory blood pressure monitoring (ABPM)
in children with IgA nephropathy and Henoch-Schonlein nephropathy (IgAN/HSN).
MATERIAL AND METHODS: In 48 children (29 with IgAN, 19 with HSN) aged 14.04 +/-
3.76 years, we evaluated retrospectively 24-hour systolic and diastolic BP
(24hSBP, 24hDBP), AASI, PP, systolic and diastolic BPV, and nocturnal BP dip by
ABPM, body mass index (BMI) Z-score, medications, and biochemical parameters. The
control group (CG) consisted of 20 healthy children aged 13.36 +/- 4.12 years.
RESULTS: AASI was 0.369 +/- 0.100 in IgAN, 0.346 +/- 0.148 in HSN, and 0.300 +/-
0.067 in the CG; AASI was significantly (p = 0.009) higher in IgAN vs. CG. PP was
higher (P = 0.04) in IgAN vs. HSN. Based on ABPM data, poorly-controlled
hypertension was found in 14 of 22 patients (63.6%) with previously diagnosed
hypertension. No differences in BPV or nocturnal BP dip were found between the
groups. In all children with IgAN/HSN, 24hDBP correlated significantly with
proteinuria, cholesterol, triglycerides, and prednisone dose; BMI Z-score
correlated with SBPV, DBPV, and PP. CONCLUSIONS: 1. Children with IgAN have
higher arterial stiffness compared to healthy peers. 2. In children with
IgAN/HSN, proteinuria and hyperlipidemia are risk factors for elevated diastolic
blood pressure, while obesity is a risk factor for increased blood pressure
variability and pulse pressure. 3. Pediatric patients with IgAN/HSN require
regular ABPM evaluation to allow for early detection of poor pharmacological
control of hypertension.?.
PMID- 28406084
TI - Evidence that TmP/GFR can be estimated with the Walton-Bijvoet nomogram in
chronic kidney disease?.
AB - BACKGROUND: The Walton-Bijvoet nomogram incorporates the assumption that GFR =
creatinine clearance (Ccr). It determines phosphate tubular maximum per volume of
filtrate (TmP/GFR) from serum phosphorus ([P]s) and fractional excretion of P
(FEP), and equates TmP/GFR with actual reabsorption per volume of filtrate
(TRP/Ccr) at FEP >= 20%. It has not been validated in chronic kidney disease
(CKD). METHODS: We studied 28 controls and 30 patients with stages 3 - 4 CKD.
From samples of serum (s) and urine (u), we calculated P excretion per volume of
filtrate (EP/Ccr) as [P]u[cr]s/[cr]u, TRP/Ccr as [P]s - EP/Ccr, and FEP as
[P]u[cr]s/[P]s [cr]u or 1/{1 + (TRP/Ccr)/(EP/Ccr)}. Because a plot of TRP/Ccr
against EP/Ccr resembled a hyperbola, we performed a linear regression of TRP/Ccr
on 1/(EP/Ccr). From the resulting equation, we derived a hyperbolic formula
relating TRP/Ccr to EP/Ccr; from that formula, we calculated TRP/Ccr and FEP as
functions of EP/Ccr. RESULTS: The regression of TRP/Ccr on 1/(EP/Ccr) was
significant. The horizontal limb of the derived hyperbola commenced at FEP ? 20%
and depicted stable P reabsorption at FEP > 20%. CONCLUSIONS: TRP/Ccr was a
hyperbolic function of EP/Ccr over a wide range of GFR. Like the Walton-Bijvoet
nomogram, this function projected a near-constant TRP/Ccr - i.e., a TmP/GFR - at
FEP > 20%. The nomogram depicts TmP/GFR accurately in CKD.?.
PMID- 28406085
TI - A single center kidney transplant experience among ten Caucasian females with end
stage renal disease due to scleroderma?.
AB - There is limited information on kidney transplant recipients with end-stage renal
disease (ESRD) due to scleroderma. We conducted an observational study on kidney
transplant recipients with ESRD due to scleroderma who received kidney transplant
at our center between 01/1994 and 06/2013. During the study period, there were 10
kidney transplant recipients, all of whom were Caucasian females. Seven of them
were living-donor kidney transplant recipients, and the mean age at time of
transplant was 56.6 +/- 11.99 years. The mean post-transplant follow-up was 76.75
+/- 56.18 months; the mean dialysis vintage was 46.4 +/- 80.35 months, ranging
from 8 to 272 months; and the mean serum creatinine (Cr) levels at 3, 6, and 12
months were 1.31 +/- 0.47 mg/dL, 1.35 +/- 0.51 mg/dL, and 1.34 +/- 0.49 mg/dL,
respectively. There were 5 graft failures with median graft survival of 101
months. None had recurrence of scleroderma renal crisis. In those without graft
failure, the mean serum Cr at last follow-up was 0.96 +/- 0.39 mg/dL. Six
patients were on angiotensin converting enzyme inhibitors (ACE-I) after
transplant. In univariate analysis, none of the factors including, age at time of
transplant, dialysis vintage, use of ACE-I, living-donor transplant,
cytomegalovirus infection, and serum Cr at 1 year were predictive of graft
failure. In our study, we hoped to find outcomes and various factors associated
with graft failure in these patients. We found a wide variation in outcomes after
kidney transplantation. More studies are needed to assess the factors that may
influence the graft survival in this rare disease.?.
PMID- 28406086
TI - Postprandial serum C-peptide level is associated with increased urinary albumin
to-creatinine ratio in patients with type 2 diabetes mellitus.
PMID- 28406087
TI - A case of Crimean-Congo hemorrhagic fever in a chronic hemodialysis patient.
PMID- 28406089
TI - Patterns of benzodiazepine prescribing by neuropsychiatrists and general
practitioners for elderly patients in Germany in 2014?.
AB - BACKGROUND: The patterns of benzodiazepine prescriptions in older adults are of
general and scientific interest as they are not yet well understood. The aim of
this study was to compare the prescription patterns of benzodiazepines in elderly
people in Germany to determine the share or proportion treated by general
practitioners (GP) and neuropsychiatrists (NP). METHODS: This study included
31,268 and 6,603 patients between the ages of 65 and 100 with at least one
benzodiazepine prescription in 2014 from GP and NP, respectively. Demographic
data included age, gender, and type of health insurance coverage. The share of
elderly people with benzodiazepine prescriptions was estimated in different age
and disease groups for both GP and NP patients. The share of the six most
commonly prescribed drugs was also calculated for each type of practice. RESULTS:
The share of people taking benzodiazepines prescribed by GP increased from 3.2%
in patients aged between 65 and 69 years to 8.6% in patients aged between 90 and
100 years, whereas this share increased from 5.4% to 7.1% in those seen by NP.
Benzodiazepines were frequently used by patients suffering from sleep disorders
(GP: 33.9%; NP: 5.5%), depression (GP: 17.9%; NP: 29.8%), and anxiety disorders
(GP: 14.5%; NP: 22.8%). Lorazepam (30.3%), oxazepam (24.7%), and bromazepam
(24.3%) were the three most commonly prescribed drugs for GP patients. In
contrast, lorazepam (60.4%), diazepam (14.8%), and oxazepam (11.2%) were those
more frequently prescribed to NP patients. CONCLUSION: Prescription patterns of
benzodiazepine in the elderly varied widely between GP and NP.?.
PMID- 28406088
TI - Population pharmacokinetics of vancomycin in Chinese infants?.
AB - OBJECTIVE: To determine the pharmacokinetics (PK) of vancomycin in Chinese infant
patients using a population pharmacokinetic (PKK) approach in order to provide
support for individualized vancomycin therapy. METHOD: The data included 72 sets
of steady-state peak and trough serum concentrations from 61 infants (0 - 1
years). PPK analysis was performed using the nonlinear mixed-effects modeling
software. Inter- and intraindividual variability was estimated for the clearance
and distribution volume of vancomycin. The potential effects of patient sex,
postnatal age, postconceptional age, height, weight, body surface area, body mass
index, alanine aminotransferase, aspartate aminotransferase, total protein,
albumin, white blood cell count, serum creatinine, and concomitant medications on
vancomycin PKs were explored. RESULTS: A one-compartment linear model with first
order elimination was used to describe the data. Weight and postnatal age had a
significant influence on vancomycin clearance. The typical population parameter
estimates of clearance and distribution volume were 0.46 L/h and 4.45 L,
respectively. Goodness-of-fit plots and bootstrap outcomes confirmed the
relatively good stability and prediction capability of the model. CONCLUSION:
This study initially established a vancomycin PPK model to estimate individual PK
parameters in Chinese infant patients.?.
PMID- 28406090
TI - Pharmacokinetic comparison using two tablets of an evogliptin/metformin XR
2.5/500 mg fixed dose combination vs. 1 tablet each of evogliptin 5 mg and
metformin XR 1,000 mg?.
AB - OBJECTIVES: The aim of this study was to compare the pharmacokinetic (PK)
characteristics of evogliptin and metformin following the administration of 2
evogliptin/metformin extended-release (XR) 2.5/500 mg FDC tablets with the
coadministration of separate evogliptin 5-mg and metformin XR 1,000-mg tablets
(separate formulations). METHODS: A randomized, two-period, two-sequence
crossover study was conducted. Subjects were randomly assigned to receive 2 FDC
tablets or the individual tablets, followed by a 14-day washout period and the
administration of the alternate treatment. Blood samples were collected predose
and up to 72 hours postdose for each period. PK parameters including
Cmax and AUClast were calculated. The geometric mean ratios
(GMRs) and the 90% confidence intervals (CIs) between FDC and the separate
formulations were calculated for the Cmax and AUClast of
evogliptin and metformin. RESULTS: 33 subjects completed the study. The GMR (90%
CI) values of Cmax and AUClast for evogliptin were 1.011
(0.959 - 1.066) and 1.010 (0.977 - 1.043), respectively. The GMR (90% CI) values
of Cmax and AUClast for metformin were 0.892 (0.827 -
0.963) and 0.893 (0.841 - 0.947), respectively. There was no significant
difference between the FDC and separate formulations regarding the occurrence of
adverse events. All drug-related adverse events were considered to be mild and
resolved without any treatment. CONCLUSIONS: Two FDC tablets of
evogliptin/metformin XR 2.5/500 mg showed a similar PK profile to the separate
formulations of evogliptin 5 mg and metformin XR 1,000 mg. All of the 90% CIs of
GMR satisfied the regulatory bioequivalence criteria of 0.800 - 1.250.?.
PMID- 28406091
TI - Daptomycin-associated eosinophilic pneumonia with rechallenge: a case report?.
AB - PURPOSE: A case of daptomycin-associated acute eosinophilic pneumonia (AEP) with
positive rechallenge is reported. SUMMARY: AEP associated with daptomycin is
reported in the literature, and the product labeling contains a warning and
precaution statement. Criteria for diagnosing daptomycin-induced AEP varies and
generally includes bronchoalveolar lavage (BAL) eosinophils >= 25%. We report a
case of a 70-year-old woman with cough, shortness of breath, and altered mental
status who presented ~ 9 days after starting therapy with daptomycin to treat
methicillin-resistant Staphylococcus aureus (MRSA)
osteomyelitis. Daptomycin was utilized because of a presumed vancomycin allergy.
Aspiration pneumonia was suspected and IV ampicillin and sulbactam was initiated.
Clinical status improved initially but ~ 1 week later, her respiratory status
declined. During work-up, peripheral eosinophils were abnormal at 11.6%, so
daptomycin therapy was discontinued. BAL revealed 5% eosinophils with negative
infectious work-up. Respiratory status rapidly improved after discontinuation of
daptomycin. Linezolid therapy was initiated. Due to an uncertain association with
daptomycin and concerns associated with long-term linezolid therapy, the patient
agreed to rechallenge with daptomycin. Within 24 hours, respiratory symptoms
returned and daptomycin was permanently discontinued. The patient rapidly
recovered without the need for systemic corticosteroid treatment. CONCLUSIONS:
Our case supports a broadened definition of pulmonary eosinophilia associated
with daptomycin administration. It is important for clinicians to consider
daptomycin as an etiology of pneumonia with abnormal eosinophils when other
causes have been excluded. Clinicians could also consider peripheral eosinophilia
as a possible indication of AEP when BAL is not available or cannot be
obtained.?.
PMID- 28406092
TI - Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel
disease naive to thiopurine treatment?.
AB - OBJECTIVES: To determine if 6-mercaptopurine (MP) is better tolerated than
azathioprine (AZA) as the initial thiopurine treatment in patients suffering from
inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is
advocated in patients intolerant to AZA. However, no study has determined if MP
is more suited than AZA as a first-line treatment for patients who are naive to
thiopurine treatment. STUDY: The tolerance of AZA and MP treatments in clinical
practice was retrospectively evaluated from start to 12 months after initiating
treatment in 113 patients with IBD who were all naive to thiopurines (82 patients
treated with AZA and 31 patients with MP). RESULTS: 65% of the patients treated
with AZA and 61% of the patients treated with MP tolerated their treatment during
12 months (i.e., no group difference, p = 0.742). No difference in reported side
effects between the two treatments was observed. The mean equivalent initial dose
(0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98
vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA
group. The proportion of patients with DeltaMCV >= 7 at 12 months was numerically
higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090).
CONCLUSIONS: In this retrospective observational study, no differences in
tolerance or adherence between AZA and MP were observed in patients naive to
thiopurines. However, MP treatment was at a higher equivalent thiopurine dose
than AZA treatment, which tended to be associated with better treatment
response.?.
PMID- 28406093
TI - Antiviral activity of nobiletin against chikungunya virus in vitro.
AB - BACKGROUND: Chikungunya virus (CHIKV), a highly contagious re-emerging virus, is
transmitted by infected mosquitoes. CHIKV is prevalent in tropical countries and
is continuing to creep farther north into temperate areas. CHIKV is responsible
for induction of chikungunya fever (CF) and severe joint stiffness with the
capability of developing into bilateral and systemic arthralgia or even
encephalitis. Despite the high morbidity rate, no approved antiviral drug is
available. Therefore, an anti-CHIKV therapy is necessary to control this disease.
In this study, we screened four flavonoids for anti-CHIKV activities: nobiletin,
phlorizin, resveratrol and oxyresveratrol. METHODS: We performed MTT, Viral
ToxGloTM and lactate dehydrogenase (LDH) assays to assess the viability of CHIKV
infected host cells. Plaque assay and immunofluorescent assay were utilized to
evaluate the levels of viral production in quantification and qualification,
respectively. RESULTS: We first confirmed that nobiletin can maintain the
cellular survival of infected cells without inducing significant toxicity to host
cells. Nobiletin suppressed virus-induced cell death and viral production. Also,
the antiviral efficacy of nobiletin can last for at least 48 h during infection.
More importantly, nobiletin inhibited CHIKV infection during the
translation/replication stages and viral entry, making nobiletin a potential
clinical antiviral agent in prophylaxis and post-exposure treatment. CONCLUSIONS:
In this study, our results provided a strategy to develop anti-chikungunya agents
by utilizing natural compounds. Also, we believe that nobiletin can be a
potential antiviral agent against CHIKV infection worthy of being further
investigated as a remedial candidate in vivo.
PMID- 28406094
TI - The role of cell body density in ruminant retina mechanics assessed by atomic
force and Brillouin microscopy.
AB - Cells in the central nervous system (CNS) respond to the stiffness of their
environment. CNS tissue is mechanically highly heterogeneous, thus providing
motile cells with region-specific mechanical signals. While CNS mechanics has
been measured with a variety of techniques, reported values of tissue stiffness
vary greatly, and the morphological structures underlying spatial changes in
tissue stiffness remain poorly understood. We here exploited two complementary
techniques, contact-based atomic force microscopy and contact-free Brillouin
microscopy, to determine the mechanical properties of ruminant retinae, which are
built up by different tissue layers. As in all vertebrate retinae, layers of high
cell body densities ('nuclear layers') alternate with layers of low cell body
densities ('plexiform layers'). Different tissue layers varied significantly in
their mechanical properties, with the photoreceptor layer being the stiffest
region of the retina, and the inner plexiform layer belonging to the softest
regions. As both techniques yielded similar results, our measurements allowed us
to calibrate the Brillouin microscopy measurements and convert the Brillouin
shift into a quantitative assessment of elastic tissue stiffness with optical
resolution. Similar as in the mouse spinal cord and the developing Xenopus brain,
we found a strong correlation between nuclear densities and tissue stiffness.
Hence, the cellular composition of retinae appears to strongly contribute to
local tissue stiffness, and Brillouin microscopy shows a great potential for the
application in vivo to measure the mechanical properties of transparent tissues.
PMID- 28406095
TI - A giant phyllodes tumor of the breast causing severe disfigurement. A case
report.
AB - : Phyllodes tumours (PTs) are rare fibroepithelial neoplasms representing about
0,2% to 2% of all breast tumors with an incidence of about 2.1 per million. The
classification proposed by the World Health Organization for PTs into benign,
borderline, and malignant is based on a combination of several histologic
features. High-grade malignant phyllodes tumors may spread by hematogenous route.
While smaller and moderate size malignant phyllodes may typically be seen,
gigantic ones with larger than 10 cm in diameter are very rare. We report an
unusual case of a giant malignant phyllodes tumor with metastases that grew over
a 6 years period causing significant ulceration, body disfigurement and physical
transformation. Our experience indicated that surgical treatment of malignant
phyllodes tumor might be an option for improving patients' quality of life,
regardless of the extremely poor prognosis. KEY WORDS: Breast, Malignant
phyllodes tumor, Surgical treatment.
PMID- 28406098
TI - Obituary - Dr. Rogayah Ja'afar.
PMID- 28406096
TI - Co-Editors' Notes 29:3.
PMID- 28406099
TI - Dr. Donald Pathman.
PMID- 28406100
TI - Medication calculation and administration workshop and hurdle assessment
increases student awareness towards the importance of safe practices to decrease
medication errors in the future.
AB - BACKGROUND: Medication errors are the second most frequently reported hospital
incident in Australia and are a global concern. A "Medication Calculation and
Administration" workshop followed by a "hurdle" assessment (compulsory task
mandating a minimum level of performance as a condition of passing the course)
was introduced into Year 2 of the James Cook University medical curriculum to
decrease dosage calculation and administration errors among graduates. This study
evaluates the effectiveness of this educational activity as a long-term strategy
to teach medical students' essential skills in calculating and administering
medications. METHODS: This longitudinal study used a pre- and post-test design to
determine whether medical students retained their calculation and administration
skills over a period of 4 years. The ability to apply basic mathematical skills
to medication dose calculation, principles of safe administration (Part 1), and
ability to access reference materials to check indications, contraindications,
and writing the medication order with correct abbreviations (Part 2) were
compared between Year 2 and 6 assessments. RESULTS: Scores for Parts 1, 2 and
total scores were nearly identical from Year 2 to Year 6 (P = 0.663, 0.408, and
0.472, respectively), indicating minimal loss of knowledge by students in this
period. Most Year 6 students (86%) were able to recall at least 5 of the "6
Rights of Medication Administration" while 84% reported accessing reference
material and 91% reported checking their medical calculations. DISCUSSION: The
"Medication Calculation and Administration" workshop with a combined formative
and summative assessment - a "hurdle" - promotes long-term retention of essential
clinical skills for medical students. These skills and an awareness of the
problem are strategies to assist medical graduates in preventing future
medication-related adverse events.
PMID- 28406101
TI - Emotional intelligence: A unique group training in a hematology-oncology unit.
AB - BACKGROUND: Emotional intelligence (EI) is increasingly viewed as one of the
important skills required for a successful career and personal life.
Consequently, efforts have been made to improve personal and group performance in
EI, mostly in commercial organizations. However, these programs have not been
widely applied in the health field. The aim of this study is to assess the impact
of a unique special EI interventional process within the framework of an active
hematology-oncology unit in a general hospital. METHODS: This investigation
employed a pre- and post-training design using the Bar-On Emotional Quotient
Inventory (EQ-i) measure of EI, both before and after completion of training 10
months later. The training included personal and group EI assessments and 10 EI
workshops, each 2 weeks apart and each lasting approximately 2 h. Results were
compared to a control group of medical staff who did not undergo any EI training
program during the same time period. RESULTS: Average total Bar-On EQ-i level at
baseline for the group was 97.9, which increased significantly after the
interventional process to a score of 105.6 (P = 0.001). There were also
significant increases in all five main EQ-i scales, as well as for 12 of the 15
subscales. In contrast, the control group showed no significant differences in
general EI level, in any of the five main scales or 15 EI subscale areas.
DISCUSSION: This pilot study demonstrated the capability of a group intervention
to improve EI of medical staff working in a hematology-oncological unit. The
results are encouraging and suggest that the model program could be successfully
applied in a large-scale interventional program.
PMID- 28406102
TI - Strong correlations between empathy, emotional intelligence, and personality
traits among podiatric medical students: A cross-sectional study.
AB - BACKGROUND: The ability of health-care providers to demonstrate empathy toward
their patients results in a number of positive outcomes improving the quality of
care. In addition, a provider's level of emotional intelligence (EI) can further
the doctor-patient relationship, stimulating a more personalized and
comprehensive manner of treating patients. Furthermore, personality traits of a
clinician may positively or negatively influence that relationship, as well as
clinical outcomes. This study was designed to evaluate empathy levels in
podiatric medical students in a 4-year doctoral program. Moreover, this study
aimed to determine whether EI, personality traits, and demographic variables
exhibit correlations with the observed empathy patterns. METHODS: This cross
sectional study collected data using an anonymous web-based survey completed by
150 students registered at the New York College of Podiatric Medicine. There were
four survey sections: (1) demographics, (2) empathy (measured by the Jefferson
Scale of Physicians' Empathy), (3) EI (measured by the Assessing Emotions Scale),
and (4) personality traits (measured by the NEO-Five-Factor Inventory-3).
RESULTS: Empathy levels were significantly correlated with EI scores (r = 0.62, n
= 150, P< 0.0001). All the five domains of personality were also shown to
correlate with empathy scores, as well as with EI scores. With respect to
demographics, Asian-American students had lower mean empathy scores than students
of other races (P = 0.0018), females had higher mean empathy scores compared to
men (P = 0.001), and undergraduate grade point average correlated with empathy
scores in a nonmonotonic fashion (P = 0.0269). DISCUSSION: When measuring the
variables, it was evident that there was a strong correlation between empathy,
EI, and personality in podiatric medical students. Given the suggested importance
and effect of such qualities on patient care, these findings may serve as
guidance for possible amendments and warranted curriculum initiatives in medical
education.
PMID- 28406103
TI - Remote-online case-based learning: A comparison of remote-online and face-to
face, case-based learning - a randomized controlled trial.
AB - BACKGROUND: Case-based learning (CBL) is an educational approach where students
work in small, collaborative groups to solve problems. Computer assisted learning
(CAL) is the implementation of computer technology in education. The purpose of
this study was to compare the effects of a remote-online CBL (RO-CBL) with
traditional face-to-face CBL on learning the outcomes of undergraduate
physiotherapy students. METHODS: Participants were randomized to either the
control (face-to-face CBL) or to the CAL intervention (RO-CBL). The entire 3rd
year physiotherapy cohort (n = 41) at Monash University, Victoria, Australia,
were invited to participate in the randomized controlled trial. Outcomes included
a postintervention multiple-choice test evaluating the knowledge gained from the
CBL, a self-assessment of learning based on examinable learning objectives and
student satisfaction with the CBL. In addition, a focus group was conducted
investigating perceptions and responses to the online format. RESULTS: Thirty
eight students (control n = 19, intervention n = 19) participated in two CBL
sessions and completed the outcome assessments. CBL median scores for the
postintervention multiple-choice test were comparable (Wilcoxon rank sum P =
0.61) (median/10 [range] intervention group: 9 [8-10] control group: 10 [7-10]).
Of the 15 examinable learning objectives, eight were significantly in favor of
the control group, suggesting a greater perceived depth of learning. Eighty-four
percent of students (16/19) disagreed with the statement "I enjoyed the method of
CBL delivery." Key themes identified from the focus group included risks
associated with the implementation of, challenges of communicating in, and
flexibility offered, by web-based programs. DISCUSSION: RO-CBL appears to provide
students with a comparable learning experience to traditional CBL. Procedural and
infrastructure factors need to be addressed in future studies to counter student
dissatisfaction and decreased perceived depth of learning.
PMID- 28406104
TI - Institutionalized physical activity curriculum benefits of medical students in
Colombia.
AB - BACKGROUND: Health authorities internationally have recommended implementing
physical activity and exercise for health training programs within the curriculum
of medical schools. The purpose of this evaluation was to determine the changes
in physical fitness and health (Fitnessgram criteria) of a sports medicine and
physical activity course implemented for 3rd year students in a private medical
school in Bogota, Colombia. METHODS: Intervention was targeted to 13 medical
student cohorts. Cardiovascular endurance (20 m shuttle run test), speed (20 m
sprint), strength (push-ups and curl-ups in 30 s), and flexibility (sit and
reach) were evaluated at the beginning and end of the school semester. It was a
54 semester-hour intervention (3 h/week), with 37 h (69%) of directed group-based
physical exercise. RESULTS: Five hundred and twenty-four students were evaluated
with an average age of 20 +/- 1.4 years; 341 (65.1%) were women. In all the
fitness tests for men and women, a significant increase was found. The prevalence
of a healthy cardiorespiratory capacity went from 47.8% to 89.1% in women (P <
0.001) and from 54.6% to 83.1% in men (P < 0.001). Body mass index and weight
increased in both sexes. DISCUSSION: The results of the current study showed that
a 54 h physical activity course within the medicine curriculum had a positive
impact on health-related fitness indicators in Colombian medical students.
PMID- 28406105
TI - Patients' feelings about the presence of medical students in a New Teaching
Hospital in Southwestern Nigeria.
AB - BACKGROUND: This study aimed to evaluate how patients feel about the introduction
of medical students into a former general hospital transformed to a teaching
hospital in southwestern Nigeria and to also assess the extent to which they are
willing to involve medical students in the management of their conditions.
METHODS: In a descriptive cross-sectional study, a sample of 251 randomly
selected patients were interviewed using a pretested questionnaire that assessed
patients' demography, patients' acceptance of and reaction to the involvement of
medical students in their clinical care including the specific procedures the
patients would allow medical students to perform. RESULTS: Two hundred and fifty
one patients with mean age +/- standard deviation of 37.33 +/- 19.01 (age range =
16-120 years; M:F = 1:1.26) were recruited between January 01 and March 31, 2013.
Most patients (86.5%) preferred to be treated in a teaching hospital and were
comfortable with medical students as observers (83.7%) and serving as the
doctors' assistant (83.3%) during common diagnostic procedures. Men were more
willing to have invasive procedures such as insertion of urinary catheter (56.6%
vs. 43.4%, P = 0.001). Acceptability of medical students (such as willingness of
patients to have students read their medical notes) was significantly higher in
nonsurgical specialties than in surgical specialties (77.5% vs. 22.5%, P< 0.001).
Factors associated with a positive disposition include age> 40 years, male
gender, and higher level of education as well as consultation in nonsurgical
specialties (P = 0.001). DISCUSSION: Medical students are well received into this
new teaching hospital setting. However, there is a need for more education of
younger, less educated female patients of surgical subspecialties so that they
can understand their importance as irreplaceable partners in the training of
medical students.
PMID- 28406106
TI - Using forum play to prevent abuse in health care organizations: A qualitative
study exploring potentials and limitations for learning.
AB - BACKGROUND: Abuse in health care organizations is a pressing issue for
caregivers. Forum play, a participatory theater model, has been used among health
care staff to learn about and work against abuse. This small-scale qualitative
study aims to explore how forum play participants experience the potentials and
limitations of forum play as an educational model for continued professional
learning at a hospital clinic. METHODS: Fifteen of 41 members of staff of a
Swedish nephrology clinic, primarily nurses, voluntarily participated in either
one or two forum play workshops, where they shared experiences and together
practiced working against abuse in everyday health care situations. Interviews
were conducted after the workshops with 14 of the participants, where they were
asked to reflect on their own and others' participation or nonparticipation, and
changes in their individual and collective understanding of abuse in health care.
RESULTS: Before the workshops, the informants were either hesitant or very
enthusiastic toward the drama-oriented form of learning. Afterward, they all
agreed that forum play was a very effective way of individual as well as
collective learning about abuse in health care. However, they saw little effect
on their work at the clinic, primarily understood as a consequence of the fact
that many of their colleagues did not take part in the workshops. DISCUSSION:
This study, based on the analysis of forum play efforts at a single hospital
clinic, suggests that forum play can be an innovative educational model that
creates a space for reflection and learning in health care practices. It might be
especially fruitful when a sensitive topic, such as abuse in health care, is the
target of change. However, for the effects to reach beyond individual insights
and a shared understanding among a small group of participants, strategies to
include all members of staff need to be explored.
PMID- 28406107
TI - Evaluating the use of twitter as a tool to increase engagement in medical
education.
AB - BACKGROUND: Social media is regularly used by undergraduate students. Twitter has
a constant feed to the most current research, news and opinions of experts as
well as organisations. Limited evidence exists that examines how to use social
media platforms, such as Twitter, effectively in medical education. Furthermore,
there is limited evidence to inform educators regarding social media's potential
to increase student interaction and engagement. AIM: To evaluate whether social
media, in particular Twitter, can be successfully used as a pedagogical tool in
an assessment to increase student engagement with staff, peers and course
content. METHODS: First year biomedical science students at Monash University
completing a core public health unit were recruited into the study. Twitter
related activities were incorporated into the semester long unit and aligned with
both formative and summative assessments. Students completed a structured
questionnaire detailing previous use of social media and attitudes towards its
use in education post engagement in the Twitter-specific activities. Likert scale
responses compared those who participated in the Twitter activities with those
who did not using student's t-test. RESULTS: A total of 236 (79.4%) of invited
students participated in the study. Among 90% of students who reported previous
use of social media, 87.2% reported using Facebook, while only 13.1% reported
previous use of Twitter. Social media was accessed most commonly through a mobile
device (49.1%). Students actively engaging in Twitter activities had
significantly higher end-of-semester grades compared with those who did not [Mean
Difference (MD) = 3.98, 95% CI 0.40, 7.55]. Students perceived that the use of
Twitter enabled greater accessibility to staff, was a unique method of promoting
public health, and facilitated collaboration with peers. DISCUSSION: Use of
social media as an additional, or alternate, teaching intervention is positively
supported by students. Specific use of micro-blogs such as Twitter can promote
greater student-staff engagement by developing an ongoing academic conversation.
PMID- 28406108
TI - Specialty preferences and motivating factors: A national survey on medical
students from five uae medical schools.
AB - BACKGROUND: Workforce planning is critical for being able to deliver appropriate
health service and thus is relevant to medical education. It is, therefore,
important to understand medical students' future specialty choices and the
factors that influence them. This study was conducted to identify, explore, and
analyze the factors influencing specialty preferences among medical students of
the United Arab Emirates (UAE). METHODS: A multiyear, multicenter survey of
medical student career choice was conducted with all five UAE medical schools.
The questionnaire consisted of five sections. Chi-squared tests, regression
analysis, and stepwise logistic regression were performed. RESULTS: The overall
response rate was 46% (956/2079). Factors that students reported to be extremely
important when considering their future career preferences were intellectual
satisfaction (87%), work-life balance (71%), having the required talent (70%),
and having a stable and secure future (69%). The majority of students (60%)
preferred internal medicine, surgery, emergency medicine, or family Medicine. The
most common reason given for choosing a particular specialty was personal
interest (21%), followed by flexibility of working hours (17%). DISCUSSION: The
data show that a variety of factors inspires medical students in the UAE in their
choice of a future medical specialty. These factors can be used by health
policymakers, university mentors, and directors of residency training programs to
motivate students to choose specialties that are scarce in the UAE and therefore
better serve the health-care system and the national community.
PMID- 28406109
TI - Assessment of community-based training of medical undergraduates: Development and
validation of a competency-based questionnaire.
AB - BACKGROUND: The global shift toward competency-based education and assessment is
also applicable to community-based training (CBT) of undergraduate medical
students. There is a need for a tool to assess competencies related to CBT. This
study aimed to develop a tool that uses a competency-based approach to evaluate
CBT of medical undergraduates. METHODS: A preliminary draft of the questionnaire
was prepared by the investigators based on a conceptual framework. Using the
Delphi technique, this draft was further developed by a specialist panel (n = 8)
into a self-administered questionnaire. After pretesting with students, it was
administered to medical undergraduates (n = 178) who had recently completed
Community Medicine. Item analysis and exploratory factor analysis were performed
under which principal component analysis was used. Reliability was assessed by
calculating Cronbach's alpha, convergent validity by correlating the scores with
Community Medicine university examination scores, and construct validity by
describing percentage variance explained by the components. RESULTS: A 74-item
questionnaire developed after the Delphi technique was further abridged to a 58
item questionnaire. Cronbach's alpha of 74 and 58-item questionnaires were 0.96
and 0.95, respectively; convergent validity was 0.07 and 0.09, respectively; and
percentage variance explained by the components were 69.3% and 70.1%,
respectively. Agreement between scores of both versions was 0.76. DISCUSSION: The
authors developed a questionnaire which can be used for competency-based
assessment in community-based undergraduate medical education. It is a valuable
addition to the existing assessment methods and can guide experts in a need-based
design of curriculum and teaching/training methodology.
PMID- 28406110
TI - Effectiveness of cross-cultural education for medical residents caring for
burmese refugees.
AB - BACKGROUND: Limited resources are available to educate health professionals on
cultural considerations and specific healthcare needs of Burmese refugees. The
objective of this study was to determine the effectiveness of a module focused on
cross-cultural considerations when caring for Burmese refugees. METHODS: A brief
educational module using anonymously tracked pre- and post-intervention, self
administered surveys was developed and studied. The surveys measured pediatric
and family medicine residents' knowledge, attitudes, and comfort in caring for
Burmese refugees. Paired t-tests for continuous variables and Fisher's exact
tests for categorical variables were used to test pre- and post-intervention
differences. We included open-ended questions for residents to describe their
experiences with the Burmese population. RESULTS: The survey was available to 173
residents. Forty-four pre- and post-intervention surveys were completed (response
rate of 25%). Resident comfort in caring for Burmese increased significantly
after the module (P = 0.04). Resident knowledge of population-specific cultural
information increased regarding ethnic groups (P = 0.004), appropriate laboratory
use (P = 0.04), and history gathering (P = 0.001). Areas of improved resident
attitudes included comprehension of information from families (P = 0.03) and
length of time required with interpreter (P = 0.01). Thematic evaluation of
qualitative data highlighted four themes: access to interpreter and resources,
verbal communication, nonverbal communication, and relationship building with
cultural considerations. DISCUSSION: A brief intervention for residents has the
potential to improve knowledge, attitudes, and comfort in caring for Burmese
patients. Interventions focused on cultural considerations in medical care may
improve cultural competency when caring for vulnerable patient populations.
PMID- 28406111
TI - A survey-based study of emotional intelligence as it relates to gender and
academic performance of medical students.
AB - BACKGROUND: Emotional intelligence (EI) refers to the composite set of
capabilities that enable a person to identify, assess, understand, and control
emotions of oneself and others. This study was conducted to assess trait EI, to
examine possible differences in the EI level of medical students in terms of
gender, and to investigate the correlation between EI of medical students and
their academic performance. METHODS: We used a cross-sectional survey consisting
of a self-assessment questionnaire distributed to 200 undergraduate medical
students after informed consent. Subjects responded on a five-point Likert scale.
Data obtained were examined using descriptive frequencies, percentages, and
correlations and analyzed with SPSS software. RESULTS: Sixty-five percent of
medical students had high EI. EI was significantly higher in females (72.27+/-
8.84) compared to males (67.47+/- 15.43) (P = 0.007). There was a positive
correlation between EI and academic performance (r = 0.51). DISCUSSION: EI is a
necessary component of medical students' skill sets to ensure that they are not
only knowledgeable and academically competent in medical school but will also
succeed in the future as quality healthcare professionals. There should be a
balance between intelligence quotient and EI in students' learning processes to
ensure success both personally and professionally. Students with good EI tend to
be skilled at interpreting emotions; skills which, in turn, will add on to their
performance in medical training and patient care.
PMID- 28406112
TI - Doctors of tomorrow: An innovative curriculum connecting underrepresented
minority high school students to medical school.
AB - BACKGROUND: Racial minorities continue to be underrepresented in medicine (URiM).
Increasing provider diversity is an essential component of addressing disparity
in health delivery and outcomes. The pool of students URiM that are competitive
applicants to medical school is often limited early on by educational
inequalities in primary and secondary schooling. A growing body of evidence
recognizing the importance of diversifying health professions advances the need
for medical schools to develop outreach collaborations with primary and secondary
schools to attract URiMs. The goal of this paper is to describe and evaluate a
program that seeks to create a pipeline for URiMs early in secondary schooling by
connecting these students with support and resources in the medical community
that may be transformative in empowering these students to be stronger university
and medical school applicants. METHODS: The authors described a medical student
led, action-oriented pipeline program, Doctors of Tomorrow, which connects
faculty and medical students at the University of Michigan Medical School with
9th grade students at Cass Technical High School (Cass Tech) in Detroit,
Michigan. The program includes a core curriculum of hands-on experiential
learning, development, and presentation of a capstone project, and mentoring of
9th grade students by medical students. Cass Tech student feedback was collected
using focus groups, critical incident written narratives, and individual
interviews. Medical student feedback was collected reviewing monthly meeting
minutes from the Doctors of Tomorrow medical student leadership. Data were
analyzed using thematic analysis. RESULTS: Two strong themes emerged from the
Cass Tech student feedback: (i) Personal identity and its perceived effect on
goal achievement and (ii) positive affect of direct mentorship and engagement
with current healthcare providers through Doctors of Tomorrow. A challenge noted
by the medical students was the lack of structured curriculum beyond the 1st year
of the program; however, this was complemented by their commitment to the program
for continued longitudinal development. DISCUSSION: The authors propose that
development of outreach pipeline programs that are context specific, culturally
relevant, and established in collaboration with community partners have the
potential to provide underrepresented students with opportunities and skills
early in their formative education to be competitive applicants to college and
ultimately to medical school.
PMID- 28406113
TI - Creating a longitudinal database in medical education: Perspectives from the
pioneers.
AB - The Jefferson Longitudinal Study of Medical Education (JLSME) is the longest
running database in medical education and covers the collection and measurement
of background, learning, performance, and psychosocial variables before, during,
and after medical school. Recently, our research group at VU University Medical
Center School of Medical Sciences launched a longitudinal study in medical
education, called the "Student Motivation and Success Study." While setting up
this study, we faced many challenges and learning about the JLSME helped us gain
a fresh perspective on our work. We interviewed Drs. Joseph Gonnella and
Mohammadreza Hojat, the leaders of the JLSME, and present their experiences
verbatim in this article and summarize the lessons we learned as tips for others.
We conclude that by establishing a longitudinal database, medical educators can
test and ensure the quality of the doctors they produce, justify curricular
reforms, participate in a continuing inquiry into their educational practices,
and produce more generalizable research findings.
PMID- 28406114
TI - Everything is learning.
PMID- 28406115
TI - Medical student journals: Critical to the development of physician-scientists.
PMID- 28406116
TI - Accredited social health activists epitomize rural social change and Women's
empowerment in India.
PMID- 28406118
TI - Recent advances in the management of renal cell carcinoma-a radiation oncology
perspective.
AB - Renal cell carcinoma (RCC) is a rare cancer in developing countries like Nigeria.
However, with an increasing understanding of its epidemiology, the increasing
availability of trained personnel, improvement in diagnostic facilities, and
greater awareness in the populace, an increase in its incidence as was witnessed
in developed nations in the last few decades could be safely predicted. This
narrative review highlights the international best practices in the
multidisciplinary approach to the management of RCC, its diagnosis and treatment,
with emphasis on recent advances and radiation treatment. The National
Comprehensive Cancer Network (NCCN) guideline (version 3.2015) served as a guide
to select relevant articles through a PubMed and Google scholar query.
PMID- 28406117
TI - Beyond flexner alliance: Social mission in health professions education.
PMID- 28406119
TI - Factors affecting anxiety-fear of surgical procedures in dentistry.
AB - AIM: To compare dental anxiety and fear during procedures performed under local
anesthesia either in the operating room or in the clinic as well as to
investigate the potential factors that might influence this psychological
condition. SUBJECTS AND METHODS: Patients who were admitted to the Department of
Oral and Maxillofacial Surgery of the universities in two cities, which have a
different sociocultural patient profile, were enrolled. In addition to the State
Trait Anxiety Inventory (STAI), Dental Anxiety Scale (DAS), and Dental Fear Scale
(DFS), the patients were asked to answer the questions concerning previous dental
experience, education level, and previous psychiatric therapy. STATISTICAL
ANALYSIS USED: The results of STAI were analyzed by Mann-Whitney U-test and
results of DAS and DFS were analyzed by one-way analysis of variance test.
RESULTS: Two hundred patients, of whom 76 were enrolled in the first center and
124 were enrolled in the second center. A statistically significant difference
was observed in state anxiety levels of the patients between the two centers,
whereas the difference in trait anxiety levels was not significant. The results
of DAS, DFS, and STAI-trait (STAI-T) displayed a significant difference between
genders; the levels of anxiety and fear were higher in females than in males (DAS
P = 0.025, DFS P = 0.017, STAI-T P = 0.045). Comparison between the patients with
and without previous dental experience revealed a statistically significant
difference regarding the results of STAI. CONCLUSIONS: The study found that
sociocultural structure and gender are the significantly effective factors on
dental anxiety and fear.
PMID- 28406120
TI - Knowledge of hepatitis B virus infection among traders.
AB - INTRODUCTION: Hepatitis B virus (HBV) is a public health problem in Nigeria, with
13% of its general population having evidence of a previous or current infection.
Lack of awareness of HBV, its risk factors, and its consequences are recognized
as major deterrents to adopting positive preventive behavior including
immunization among HBV high-risk groups. OBJECTIVE: The objective of this study
is to evaluate the knowledge, attitude, and practice (KAP) of HBV infection among
traders. MATERIALS AND METHODS: A structured KAP questionnaire on HBV infection
was administered to traders as part of the activities to mark the World Hepatitis
Day in 2014. A score was created for the correct answer to 20 questions. RESULTS:
A total of 335 traders were interviewed for this study. The mean age was 33.08 +/
13.8 years and the median age was 29 years. There were 165 males and 170
females. Majority of the traders had secondary education (57.1%) and were of the
Ibibio and Igbo tribes. Only 10.4% had HBV vaccination. Only 44.2% of the traders
reported having any knowledge of HBV. The most common source for the knowledge
was television/radio (25%) and hospitals (22%). The median (interquartile range)
of the overall KAP score was low (11, 5-16). The score was least in persons aged
35 years and above, but the difference was not statistically significant (P =
0.33). CONCLUSION: The knowledge of HBV is low among traders in Calabar
metropolis. There is need to intensify educational campaigns for the general
public.
PMID- 28406121
TI - Normalization of the psychometric hepatic encephalopathy score for diagnosis of
minimal hepatic encephalopathy in Turkey.
AB - AIM: To construct normal values for the tests of the psychometric hepatic
encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic
encephalopathy (MHE) among Turkish patients with liver cirrhosis. MATERIALS AND
METHODS: One hundred and eighty-five healthy subjects and sixty patients with
liver cirrhosis without overt hepatic encephalopathy were included in the study.
All subjects underwent psychometric tests, which include number connection test-A
and B (NCT-A/B), serial dotting test (DST), line drawing test (LDT), and digit
symbol test (DST) in the same day. The variables that affected the results of the
test were included in the multiple linear regression models and formulas were
constructed to predict the expected results for each tests. RESULTS: The results
of all PHES tests, except the LDT in the cirrhotic group were significantly
different than center of gravity (CG) (P < 0,001). The score of PHES in the
cirrhotic group was -2,18 +/- 3,3 (median -2; range: 11 to +4), significantly
lower than CG (-0.31 +/- 2.18 [median, 0; range, -8 to +5]) (P < 0.001). the
cutoff of PHES was set -4 point. Therefore, 19 of the 60 cirrhotic patients were
diagnosed with MHE (31.6%). Among the patients with MHE, 11 (11/45, 24,4%) had
Child-Pugh classification (CTP) A and 8 (8/15, 53.3%) had CTP B. No differences
in age and education years were found between the MHE and non-MHE groups (P >
0.05). CONCLUSION: Turkish PHES normograms have been developed for detecting
patients with MHE. Future multicenter national studies are needed to validate
widely applicable norms.
PMID- 28406122
TI - Effects of 810-nanometer diode laser as an adjunct to mechanical periodontal
treatment on clinical periodontal parameters and gingival crevicular fluid volume
of residual periodontal pockets.
AB - BACKGROUND: Aim of this randomized controlled parallel-designed study was to
evaluate the effects of diode laser as an adjunct to mechanical periodontal
treatment on clinical parameters and gingival crevicular fluid (GCF) volume of
the residual pockets diagnosed following initial periodontal treatment in chronic
periodontitis (CP) patients. MATERIALS AND METHODS: A total of 84 residual
pockets on single-rooted teeth in 11 CP patients were included and randomly
assigned into three groups. Residual pockets were treated either only by
mechanical treatment (Group M) (n = 28) or only by diode laser disinfection
(Group L) (n = 28) or by a combination of these techniques (Group M + L) (n =
28). Plaque index, gingival index (GI), bleeding on probing (BoP), probing depth
(PD), clinical attachment level and gingival recession were assessed at baseline
and 8 weeks after treatment of residual pockets. GCF samples were collected at
baseline, 1 and 8 weeks after treatment. RESULTS: All treatment modalities
resulted in significant reductions in PD and attachment gain. GI and BoP showed a
greater reduction in both Group M and Group M + L than Group L (P < 0.001), but
there was no difference between the Groups M and M + L (P > 0.05). No difference
was also found among groups for other clinical parameters. GCF volume decreased
significantly in the Groups M and M + L (P < 0.05) but there was no difference
among the groups (P > 0.05). CONCLUSION: Results demonstrated clinical
improvements on residual pockets in CP patients treated with all three
modalities. Moreover, our findings suggest that application of diode laser as an
adjunct to mechanical periodontal treatment doesn't demonstrate any additional
clinical effect on the residual pockets.
PMID- 28406123
TI - Utilization of glial fibrillary acidic protein and galectin-3 in the diagnosis of
cerebral infarction patients with normal cranial tomography.
AB - OBJECTIVE: It was aimed to determine whether levels of glial fibrillary acidic
protein (GFAP) and Galectin-3 contribute to the diagnosis of cerebral infarction
in clinically suspected ischemic stroke patients with normal computerized cranial
tomography (CCT) in the emergency department. MATERIALS AND METHODS: In this
study, patients above the age of 18 years who presented to emergency department
of Firat University between December 2011-November 2012 and were diagnosed with
cerebral infarction were included. Exclusion criteria were as follows: symptom
onset exceeding 24 hours, trauma, pregnancy, acute myocardial infarction, acute
pulmonary embolism, chronic renal insufficiency and steroid therapy. RESULTS: A
total of 90 participants, forty patients with ischemic infarction who were
diagnosed by CCT and clinical findings (Normal CCT in 17 patients and CCT with an
area of infarction in 23 patients) and fifty healthy controls, were included in
this study. Compared with the control group, levels of Galectin-3 and GFAP were
found to be significantly increased in patients with ischemic infarction (P
<0.001 and P = 0.01, respectively). It was found that levels of Galectin-3 and
GFAP were significantly increased in ischemic stroke patients with normal CCT
compared to the control group (P = 0.04 and P = 0.025, respectively). In ROC
curve analysis, we detected %70.59 sensitivity and 70% specificity (AUC = 0.684,
P = 0.0213, 95% CI: 0,558-0.792) with a cutoff value of 33.24 ng/ml for GFAP and
76.47% sensitivity and 68% specificity (AUC = 0.734, P = 0.0048, 95% CI: 0.611
0.834) with a cutoff value of 0.84 ng/ml for Galectin-3. No correlation was found
between National Institutes of Health Stroke Scale (NIHSS) scores and Galectin-3
and GFAP (r = 0.251, P = 0.118 and r = 0.164, P = 0.311, respectively).
CONCLUSION: The levels of Galectin-3 and GFAP were increased in acute ischemic
stroke patients.
PMID- 28406124
TI - Comparison of patients with and without intellectual disability under general
anesthesia: A retrospective study.
AB - BACKGROUND AND PURPOSE: We analyzed and retrospectively compared patients with
and without intellectual disability (ID) who underwent oral surgery under general
anesthesia at Istanbul University, Faculty of Dentistry, Department of General
Anesthesia, between October 2012 and June 2013 with regard to the following
categories: Demographic features, American Society of Anesthesiologists (ASA)
classification, Mallampati score, type of anesthetic drug used during the
operation, type of intubation used, any difficulties with tracheal intubation,
presence of systemic diseases, and recovery times after ending general
anesthesia. MATERIALS AND METHODS: A total of 348 patients were selected from the
Department of Maxillofacial Surgery and the Department of Pedodontics who
underwent surgery with general anesthesia. Medical histories of all patients were
taken, and their electrocardiography, chest X-rays, complete blood count, and
blood clotting tests were checked during a preoperative assessment. Mallampati
evaluations were also performed. Patients were grouped into ASA I, II, or III
according to the ASA classification and were treated under general anesthesia.
RESULTS: There was no significant difference between normal and intellectually
disabled patients in terms of gender, Mallampati scores, intubation difficulties,
mean anesthetic period, time to discharge, or postoperative nausea and vomiting.
Epilepsy and genetic diseases in intellectually disabled patients were
significantly more common than in non-ID (NID) patients. However, the frequency
of diabetes and chronic obstructive pulmonary disease in NID patients was
significantly higher than in the intellectually disabled patients. CONCLUSION:
Dental treatment of intellectually disabled patients under general anesthesia can
be performed just as safely as that with NID patients.
PMID- 28406125
TI - Effect of rosuvastatin on dyslipidemia and other parameters associated with
metabolic syndrome in Saudi patients.
AB - CONTEXT: Metabolic syndrome (MS) is a constellation of metabolic irregularities
consisting of dyslipidemia, hypertension, hyperglycemia, chronic inflammatory,
and hypercoagulable state predisposing to diabetes and cardiovascular events.
Statins are first-line drugs to treat the associated atherogenic dyslipidemia.
AIM: Effect of rosuvastatin on MS in Saudi patients was studied. SETTINGS AND
DESIGN: Prospective, open label, randomized clinical study. MATERIALS AND
METHODS: Patients of either sex >=18 years (n = 153) having MS as per modified
National Cholesterol Education Program Adult Treatment Panel III criteria were
prescribed rosuvastatin 10 mg OD for 24 weeks. Serum lipids, biochemical,
clinical, and anthropometric parameters were studied before and after treatment.
STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences version17 was
used. Descriptive analysis was used for all variables and documented as mean +/-
SD. Normality checked by Shapiro-Wilk test, Kurtosis and Skewness Z-score, and
visualization of histograms. Lipid levels and other parameters before and after
treatment were evaluated by paired t-test for parametric data and Wilcoxon signed
rank test for nonparametric data. Pre- and post-test values were correlated by
Pearson's correlation coefficient. Multiple regression analysis was performed to
see effect of other variables. RESULTS: Highly significant reduction was observed
in low density lipoprotein cholesterol, total cholesterol, triglycerides; very
low density lipoprotein cholesterol, non-high density lipoprotein cholesterol and
atherosclerotic index with an elevation in high density lipoprotein cholesterol.
A total of 86% patients reached low density lipoprotein cholesterol goal of <=
100 mg/dL. Beneficial response was observed on other associated parameters. There
was strong correlation between pre- and post values. No significant effect was
observed for any of the variables on cholesterol reduction. No serious/severe
adverse effect was observed. CONCLUSION: Rosuvastatin markedly improved
atherogenic dyslipidemia of MS.
PMID- 28406126
TI - Correlation between international prostate symptom score and uroflowmetry in
patients with benign prostatic hyperplasia.
AB - OBJECTIVE: To determine the correlation between severity of symptoms using the
International Prostate Symptom Score (IPSS) and uroflowmetry in patients with
lower urinary tract symptoms-benign prostatic hyperplasia (LUTS-BPH). PATIENTS
AND METHODS: We prospectively collected data from 51 consecutive men, who
presented with LUTS-BPH at the Nnamdi Azikiwe University Teaching Hospital,
Nnewi, Nigeria, from January 2012 through December, 2014. Symptom severity was
assessed using the self-administered IPSS questionnaire. We also performed
uroflowmetry using the Urodyn 1000 (Dantec, serial no. 5534). RESULTS: The mean
age of the patients was 67.2 +/- 9.7 years (range 40-89 years). The most common
presenting IPSS-LUTS was nocturia (100%) followed by urinary frequency (98%),
straining (92.0%), weak stream (84.3%), urgency (41.2%), incomplete voiding
(39.2%), and intermittency (35.3%) Most of the patients had moderate symptoms
(58.8%) on IPSS with a mean value of 13.5 +/- 3.0. The mean Qmax was 15.6 +/-
18.7 mL/s and the mean voided volume was 193.0 +/- 79.2 mL. About one-third of
the patients (39.2%) had an unobstructed flow pattern based on Qmax. Correlation
analysis showed a weak correlation between IPSS and voiding time (r = 0.220, P >
0.05), flow time (r = 0.128, P > 0.05), and time to maximum flow (r = 0.246, P >
0.05). These correlations were not significant (P > 0.05). IPSS showed a negative
correlation with maximum flow rate (r = 0.368; P < 0.0075), average flow rate (
0.203, P > 0.05), and voided volume (r = -0.164, P > 0.05). This negative
correlation was significant for maximum flow rate. CONCLUSION: Correlation
between IPSS and Qmax was negative but statistically significant. This implies
that an inverse relationship exists between IPSS and Qmax, and remains the only
important parameter in uroflowmetry. There was no statistically significant
correlation between IPSS and the other variables of uroflowmetry.
PMID- 28406127
TI - Masticatory efficiency of shortened dental arch subjects with removable partial
denture: A comparative study.
AB - OBJECTIVE: The objective of this study was to compare the masticatory efficiency
in subjects with shortened dental arch (SDA) before and after restoration with
removable partial denture (RPD). MATERIALS AND METHODS: This was a prospective
study carried out on 36 consecutive patients. The subjects were asked to chew 5 g
of a measured portion of fresh raw carrot for 20 specified numbers of strokes.
The raw carrot was recovered into a cup and strained through a standard mesh
sieve of 5 mm by 1 mm, it was air dried for 30 min and weighed with FEM digital
series weighing scale. The masticatory performance ratio was then determined.
RESULT: The age range of the subjects was 34-64 years with the mean age being
52.2 +/- 8.2 years. The difference between the total masticatory performance
score at the post- and pre-treatment phases was statistically significant (P =
0.001). The improvement in masticatory performance was marked among the younger
age groups (P = 0.001), unilateral free end saddle subjects (P = 0.001), and
among the male gender (P < 0.05). CONCLUSION: Masticatory performance improved
with the provision of RPD. However, the improvement was marked among the younger
age groups, unilateral free end saddle subjects, and the male gender; thereby
supporting the need for RPDs in patients with SDA.
PMID- 28406128
TI - Variations in the beta-globin genes of sickle cell anaemia patients in Zaria,
Northwestern, Nigeria.
AB - CONTEXT: Sickle Cell Anaemia (SCA) is a genetic disorder with a life-long
disability, which is of public health importance. The diversity in its clinico
pathologic and laboratory presentations may be due to the interplay between
additional genetic differences and environmental factors. The genetic factors may
be within the beta-globin gene itself, the beta-globin gene cluster or elsewhere
in the genome. AIM: To characterize the beta-globin gene for variations
associated with the Sickle Cell mutation. SETTINGS AND DESIGN: A cross-sectional
descriptive study involving 51 adult SCA patients attending Sickle Cell Clinic of
Haematology Department Ahmadu Bello University (ABUTH) Zaria, Kaduna State,
Nigeria. METHODS AND MATERIAL: The buccal swab specimens were collected and beta
globin gene DNA sequencing was done. The sequences obtained were compared with a
Genbank Reference beta-globin gene (NC_000011.9) using Basic Local Alignment
Search Tool (BLAST), and variations noted. Data generated were analyzed using
SPSS Version 20.0. STATISTICAL ANALYSIS USED: Data generated was summarized by
using charts, means+/-2SD, and 95% confidence intervals. RESULTS: There were 40
(78.43%) females and 11 (21.57%) males. The mean age of the participants was
25.35 +/- 7.67 years, 95% CI (23.20, 27.51). The classic sickle cell mutation A T
was present in all participants. The mean number of beta-Globin gene variations
was 8.61+/-11.30, 95% CI (5.43, 11.78). The number of Substitutions were 122
(27.79%), insertions 184 (41.91%), and deletions 133 (30.30%). These occurred in
various combinations. The mean number of substitutions, insertions, and deletions
were 2.39+/-3.23, 3.61+/-7.66, and 2.60+/-2.46 with 95% CIs of (1.48, 3.30),
(1.45, 5.76), and (1.92, 3.30) respectively. CONCLUSIONS: There are beta-globin
gene variations in SCA patients in Zaria, and locally relevant genetic database
of the SCA population will be the cornerstone in understanding genotype-phenotype
interactions in this disorder.
PMID- 28406129
TI - Prevention of alveolar osteitis after third molar surgery: Comparative study of
the effect of warm saline and chlorhexidine mouth rinses.
AB - BACKGROUND: Chlorhexidine mouth rinses have a proven efficacy for the prevention
of alveolar osteitis after third molar surgery. This study compares the efficacy
of warm saline rinse, a component of postextraction instructions, with that of
chlorhexidine in our institution over a period of 2 years. PATIENTS AND METHODS:
Apparently healthy patients who were referred to the Oral Surgery Clinic of our
institution, with an indication for surgical extraction of lower third molar were
prospectively, consecutively, and uniformly randomized into warm saline and
chlorhexidine groups. The experimental group (n = 50/100) were instructed to
gargle twice daily with warm saline, whereas the chlorhexidine group (n = 50/100)
were instructed to gargle with 0.12% chlorhexidine. Information on demographic,
types and level of impaction, indications for extraction, and development of
alveolar osteitis were obtained and analyzed. Comparative statistics were done
using Pearson's Chi-square, Fisher's exact, or Mann-Whitney U-tests as
appropriate. P <0.05 was considered statistically significant. RESULTS: The
demographic, types and level of impaction as well as indications for extractions
were comparable between the study groups (P > 0.05). The overall prevalence of
alveolar osteitis was 5%. There was no statistically significant difference
between application of warm saline and 0.12% chlorhexidine rinse with respect to
the development of alveolar osteitis (P = 0.648). CONCLUSION: Warm saline mouth
rinse is equally as effective as chlorhexidine mouth rinse, as prophylaxis
against prevention of alveolar osteitis after third molar surgery.
PMID- 28406130
TI - Is the periodontal status a risk factor for the development of psoriasis?
AB - BACKGROUND AND OBJECTIVES: Psoriasis is a common, chronic, inflammatory, and
hyperproliperative skin disease. It has been known that the infectious agents
play a role in triggering and exacerbation of the disease. Periodontal diseases
are chronic inflammatory gum diseases initiated by microorganisms in dental
plaques. This study intended to determine the role of periodontal diseases, as
chronic infective foci in psoriasis. MATERIALS AND METHODS: A total of 76
patients, who applied to Faculty of Medicine, Department of Dermatology, Inonu
University, diagnosed as psoriasis and a control group consisting of 76
dermatologic patients without any systemic disease at similar age and gender were
included the study. The dental examinations of the subjects were done by the
Community Periodontal Index of Treatment Needs index system, using a periodontal
probe. RESULTS: Significant difference was identified between the patients with
psoriasis and control group, in terms of CPI (Community Periodontal Index), oral
hygiene habits, frequency of tooth brushing and flossing (P = 0.01, P = 0.001, P
= 0.01, P = 0.05, respectively). A positive correlation between the severities of
psoriasis and dental disease was determined, but this difference was not
statistically significant (P = 0.204). CONCLUSION: The periodontal disease may
affect psoriasis as a chronic infectious focus and probably through
proinflammatory cytokines. In order to clarify the exact role of periodontal
disease in psoriasis, the issue should be studied in larger series with serum
cytokine levels.
PMID- 28406131
TI - Sleep health of healthcare workers in Kano, Nigeria.
AB - BACKGROUND: The relevance of sleep in the life of a human being cannot be
overemphasized in terms of physical and mental well-being. Among several factors
that can affect the sleep health of an individual occupation have been found to
play a prominent role. The literature is still scanty with regard to sleep
studies in our environment. AIM: This study aims to assess the sleep health of
tertiary healthcare workers in Kano Nigeria and find, if any, its determining or
related factors. MATERIAL AND METHODS: This study was cross-sectional
questionnaire-based survey and involved all consenting staff members of Aminu
Kano Teaching Hospital, Kano, Nigeria. The Pittsburgh Sleep Quality Index
Questionnaire was used to assess the sleep health of the participants. RESULTS:
The participants' ages ranged from 18 to 65 years and have a mean age of 38.94 +/
8.07 years. There were 119 (74.4%) males and 41 (25.4%) females with a M:F ratio
of 3:1 (chi2 = 19.415; P = 0.000). Among the 155 participants who completed all
the aspects of the Pittsburgh Sleep Quality Index questionnaires, the overall
sleep quality of the study population was found to be significantly poor [good
sleepers = 71 (45.8%), poor sleepers = 84 (54.2%), chi2 = 116.4; P = 0.000].
Considering the various occupational groups working in the hospital, poor sleep
was commonest among the nurses 35 (42.7%). Furthermore, among the nurses, poor
sleep was significantly commoner in those on shift work 27 (77.1%) than those not
on shift work 8 (22.9%); chi2 = 36.2; P = 0.000. Multivariate logistic regression
analysis showed that age, sex, and duration in service were not significant
predictors of poor sleep quality among the participants [odds ratio (OR) = 1.013,
95% confidence interest (CI) = 0.948-1.084, P = 0.698; OR = 0.691, 95% CI = 0.293
1.631, P = 0.399; and OR = 0.993, 95% CI = 0.932-1.058 P = 0.840, respectively).
CONCLUSIONS: Our study found that a significant proportion of healthcare workers
and particularly nurses had poor sleep quality. Also, age, sex, and duration in
service were not significant predictors of poor sleep quality among the
participants.
PMID- 28406132
TI - Role of tolterodine in the management of postoperative catheter-related bladder
discomfort: Findings in a Nigerian teaching hospital.
AB - BACKGROUND: Patient discomfort secondary to an indwelling urethral catheter in
the post operative period can be very distressing. These symptoms resemble the
overactive bladder (OAB) syndrome. Muscarinic receptor blockers have been
successful in the management of OAB. However, information on the use of these
drugs in the management of the postoperative catheter-related bladder discomfort
(CRBD) in sub-Saharan Africa is still relatively sparse. OBJECTIVE: To assess the
efficacy of preoperative oral tolterodine in the management of CRBD in surgical
patients in the immediate postoperative period. METHODS: This was a double-blind
placebo-controlled study consisting of 56 patients in each arm who underwent
general anesthesia. Each patient was given oral tolterodine or placebo 1 hour
before the induction of anesthesia. The patient was later assessed at the
recovery room at intervals after recovery from anesthesia. The presence of CRBD
was noted and graded. RESULTS: The overall incidence of CRBD in both the
tolterodine group and the control were 85.7% and 91.1%, respectively. Overall,
tolterodine prophylaxis (TP) was associated with an absolute risk reduction (ARR)
of 5.4%, relative risk reduction (RRR) of 5.8%, and a number needed to treat
(NNT) of 19. The incidence of moderate-to-severe CRBD in the tolterodine and
control groups were 10.7% and 78%, respectively, with an ARR of 74.5% with TP.
CONCLUSION: TP does not significantly reduce the incidence of CRBD in the
immediate postoperative period but appears to be efficient in the reduction of
the severity of postoperative CRBD.
PMID- 28406133
TI - Knowledge and awareness of breast cancer among rural women in Umuowa Orlu Local
Government Area Imo State, South East, Nigeria.
AB - BACKGROUND: Many women with breast cancer present at the health institutions with
advanced multiple nodal involvements have poor prognostic outcome. Knowledge and
awareness of breast cancer may promote health-seeking behavior, thus early
diagnosis and increased survival rate of breast cancer cases. The objective of
this study was to assess the level of knowledge and awareness of women on breast
self-examination (BSE) in Umuowa, which would guide future intervention program
on breast cancer prevention and control in the community. METHOD: Descriptive
survey design with the aid of a questionnaire served as an interview schedule for
the study on 349 Women in Umuoawa, Orlu Local Government Area (LGA) of Imo State.
Descriptive and inferential analysis was done using Statistical Package for
Social Sciences. RESULTS: The main outcome measure was the level of awareness on
breast cancer. With a Pearson's correlation coefficient (R) of 0.569 and a
Spearman's rank correlation coefficient (r) of 0.600 and a P value of 0.000 <
0.05, a correlation between educational attainment and BSE awareness was
established. The correlation coefficient being positive, the result showed that
with increase in educational attainment, the awareness of BSE increased and vice
versa. Thus, there was a positive relationship between educational attainment and
the awareness of BSE. One hundred and four (29.8%) respondents showed that breast
cancer is an illness caused by ancestral forces. Their knowledge of the risks
factors for breast cancer was also low. Their major source of information on
breast cancer was through health care providers followed by friends/relatives.
CONCLUSION: There is a need to scale up health education programs to remove myths
regarding breast cancer and improve health-seeking behavior among the rural
women.
PMID- 28406134
TI - Tracheobroncopathia osteochondroplastica: Three case reports with literature
review.
AB - Tracheobroncopathia osteochondroplastica (TO) is a benign disease of the large
airways seen very rarely. It is characterized by 1-3 mm sized ossified nodular
lesions in submucosa. Its etiology is unclear, but it is stated that malignancy,
chronic inflammation, amyloidosis, and genetic factors might have an effect on
it. It was first described by Wilks in a 38-year-old man diagnosed with
tuberculosis in 1857. Generally, patients are asymptomatic and TO is diagnosed
incidentally. But symptoms become significant with infections and obstruction in
tracheabronchial tree. Generally chest radiography is normal, so thorax computed
tomography can be remarkable in diagnosis of TO. Besides, final diagnosis can be
established by viewing ossified nodules in trachea and bronchus through the
fiberoptic bronchoscopy. Amyloidosis, tuberculosis, sarcoidosis, bronchial
carcinoma, and tracheobronchial calcinosis must be remembered in differential
diagnosis. Also ossifications in submucosa and proof of bone marrow in
histopathological examinations are important in diagnosis of TO. Mostly
palliative treatment is performed to the symptoms . We want the clinicians to
keep in mind for this very rarely seen tracheal disease with three case reports.
PMID- 28406135
TI - Sliding malar bone augmentation technique with a high le fort I surgically
assisted rapid maxillary expansion.
AB - The purpose of this report is to evaluate the effectiveness of a high Le Fort I
osteotomy design, including the malar bones, which allows segment sliding over
the zygoma and forces the osteotomized segment to move forward with distraction.
Two patients (male, 23-and 30-year-old) with malar deficiency underwent high Le
Fort I osteotomy and surgically assisted rapid maxillary expansion procedure was
followed. Records were taken before and 6 months after surgery for comparison,
including intra and extra oral photographs and three-dimensional cone-beam
computed tomography (CBCT) images. The bone malar width and bone malar depth
changings in malar region were evaluated. Preoperative and postoperative CBCT
images and clinical views of the patients showed forward movement of the malar
region.
PMID- 28406136
TI - Pulmonary langerhans cell histiocytosis case with diabetes insipidus and
tuberculosis.
AB - A 19-year-old male patient was observed due to having central diabetes insipidus
(DI) for five years. He had a history of smoking 5-10 cigarettes a day for two
years, but stopped smoking from the last month. The computerized tomography
revealed thin-walled cystic lesions in different sizes more dominantly in the
upper lobes and consolidated areas in the left upper and lower lobes. The wedge
resection from the right lower lobe revealed pulmonary langerhans cell
histiocytosis. Follow-up acid-fast bacteria (AFB) examinations revealed (+++) and
antituberculous treatment was started. On the 40th day of the anti-tuberculosis
treatment, the patient applied once again due to fever and chest pain. Although
infiltrations persisted in the left upper and middle zones in the postero
anterior lung rontgenogram, right-sided pneumothorax was detected. The case is
considered tuberculosis and the patient continued to receive anti-TB treatment
under the close supervision.
PMID- 28406139
TI - T-Bet independent development of IFNgamma secreting natural T helper 1 cell
population in the absence of Itk.
AB - Th1, Th2, Th9 and Th17 cells are conventional CD4+ effector T cells identified as
secretors of prototypical cytokines IFNgamma, IL4, IL9, and IL-17A respectively.
Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate
like phenotype have been identified in the thymus that are distinct from
conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin
2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and
humans. Here we show that Itk negatively regulates the development of nTh1 cells
that express IFNgamma in a Tbet independent manner, and whose expansion can be
enhanced by IL4. Furthermore, we show that robust induction of IL4 responses
during Trichinella spiralis infection enhance the presence of nTh1 cells. We
conclude T cell receptor signaling via Itk controls the development of natural
Th1 cells, which are expanded by the presence of IL4.
PMID- 28406138
TI - Inhibition of endocytic pathways impacts cytomegalovirus maturation.
AB - Endocytic processes are critical for cellular entry of several viruses; however,
the role of endocytosis in cellular trafficking of viruses beyond virus entry is
only partially understood. Here, we utilized two laboratory strains (AD169 and
Towne) of human cytomegalovirus (HCMV), which are known to use cell membrane
fusion rather than endocytosis to enter fibroblasts, in order to study a post
entry role of endocytosis in HCMV life cycle. Upon pharmacological inhibition of
dynamin-2 or clathrin terminal domain (TD) ligand association, these strains
entered the cells successfully based on the expression of immediate early viral
protein. However, both the inhibitors significantly reduced the growth rates and
final virus yields of viruses without inhibiting the expression of early to late
viral proteins. Clathrin accumulated in the cytoplasmic virus assembly
compartment (vAC) of infected cells co-localizing with virus tegument protein
pp150 and the formation of vAC was compromised upon endocytic inhibition.
Transmission electron micrographs (TEM) of infected cells treated with
endocytosis inhibitors showed intact nuclear stages of nucleocapsid assembly but
the cytoplasmic virus maturation was greatly compromised. Thus, the data
presented here implicate endocytic pathways in HCMV maturation and egress.
PMID- 28406140
TI - Spicule formation in calcareous sponges: Coordinated expression of
biomineralization genes and spicule-type specific genes.
AB - The ability to form mineral structures under biological control is widespread
among animals. In several species, specific proteins have been shown to be
involved in biomineralization, but it is uncertain how they influence the shape
of the growing biomineral and the resulting skeleton. Calcareous sponges are the
only sponges that form calcitic spicules, which, based on the number of rays
(actines) are distinguished in diactines, triactines and tetractines. Each actine
is formed by only two cells, called sclerocytes. Little is known about
biomineralization proteins in calcareous sponges, other than that specific
carbonic anhydrases (CAs) have been identified, and that uncharacterized Asx-rich
proteins have been isolated from calcitic spicules. By RNA-Seq and RNA in situ
hybridization (ISH), we identified five additional biomineralization genes in
Sycon ciliatum: two bicarbonate transporters (BCTs) and three Asx-rich
extracellular matrix proteins (ARPs). We show that these biomineralization genes
are expressed in a coordinated pattern during spicule formation. Furthermore, two
of the ARPs are spicule-type specific for triactines and tetractines (ARP1 or
SciTriactinin) or diactines (ARP2 or SciDiactinin). Our results suggest that
spicule formation is controlled by defined temporal and spatial expression of
spicule-type specific sets of biomineralization genes.
PMID- 28406141
TI - Role of Slow-Release Nanocomposite Fertilizers on Nitrogen and Phosphate
Availability in Soil.
AB - Developing efficient crop fertilization practices has become more and more
important due to the ever-increasing global demand for food production. One
approach to improving the efficiency of phosphate and urea fertilization is to
improve their interaction through nanocomposites that are able to control the
release of urea and P in the soil. Nanocomposites were produced from urea (Ur) or
extruded thermoplastic starch/urea (TPSUr) blends as a matrix in which
hydroxyapatite particles (Hap) were dispersed at ratios 50% and 20% Hap. Release
tests and two incubation experiments were conducted in order to evaluate the role
played by nanocomposites in controlling the availability of nitrogen and
phosphate in the soil. Tests revealed an interaction between the fertilizer
components and the morphological changes in the nanocomposites. TPSUr
nanocomposites provided a controlled release of urea and increased the release of
phosphorus from Hap in citric acid solution. The TPSUr nanocomposites also had
lower NH3 volatilization compared to a control. The interaction resulting from
dispersion of Hap within a urea matrix reduced the phosphorus adsorption and
provided higher sustained P availability after 4 weeks of incubation in the soil.
PMID- 28406142
TI - Simultaneous loss of interlayer coherence and long-range magnetism in quasi-two
dimensional PdCrO2.
AB - In many layered metals, coherent propagation of electronic excitations is often
confined to the highly conducting planes. While strong electron correlations
and/or proximity to an ordered phase are believed to be the drivers of this
electron confinement, it is still not known what triggers the loss of interlayer
coherence in a number of layered systems with strong magnetic fluctuations, such
as cuprates. Here, we show that a definitive signature of interlayer coherence in
the metallic-layered triangular antiferromagnet PdCrO2 vanishes at the Neel
transition temperature. Comparison with the relevant energy scales and with the
isostructural non-magnetic PdCoO2 reveals that the interlayer incoherence is
driven by the growth of short-range magnetic fluctuations. This establishes a
connection between long-range order and interlayer coherence in PdCrO2 and
suggests that in many other low-dimensional conductors, incoherent interlayer
transport also arises from the strong interaction between the (tunnelling)
electrons and fluctuations of some underlying order.
PMID- 28406143
TI - Chiral acidic amino acids induce chiral hierarchical structure in calcium
carbonate.
AB - Chirality is ubiquitous in biology, including in biomineralization, where it is
found in many hardened structures of invertebrate marine and terrestrial
organisms (for example, spiralling gastropod shells). Here we show that chiral,
hierarchically organized architectures for calcium carbonate (vaterite) can be
controlled simply by adding chiral acidic amino acids (Asp and Glu). Chiral,
vaterite toroidal suprastructure having a 'right-handed' (counterclockwise)
spiralling morphology is induced by L-enantiomers of Asp and Glu, whereas 'left
handed' (clockwise) morphology is induced by D-enantiomers, and sequentially
switching between amino-acid enantiomers causes a switch in chirality.
Nanoparticle tilting after binding of chiral amino acids is proposed as a chiral
growth mechanism, where a 'mother' subunit nanoparticle spawns a slightly tilted,
consequential 'daughter' nanoparticle, which by amplification over various length
scales creates oriented mineral platelets and chiral vaterite suprastructures.
These findings suggest a molecular mechanism for how biomineralization-related
enantiomers might exert hierarchical control to form extended chiral
suprastructures.
PMID- 28406144
TI - Nanoscale interface confinement of ultrafast spin transfer torque driving non
uniform spin dynamics.
AB - Spintronics had a widespread impact over the past decades due to transferring
information by spin rather than electric currents. Its further development
requires miniaturization and reduction of characteristic timescales of spin
dynamics combining the sub-nanometre spatial and femtosecond temporal ranges.
These demands shift the focus of interest towards the fundamental open question
of the interaction of femtosecond spin current (SC) pulses with a ferromagnet
(FM). The spatio-temporal properties of the impulsive spin transfer torque
exerted by ultrashort SC pulses on the FM open the time domain for probing non
uniform magnetization dynamics. Here we employ laser-generated ultrashort SC
pulses for driving ultrafast spin dynamics in FM and analysing its transient
local source. Transverse spins injected into FM excite inhomogeneous high
frequency spin dynamics up to 0.6 THz, indicating that the perturbation of the FM
magnetization is confined to 2 nm.
PMID- 28406145
TI - Corrigendum: DNA damage response inhibition at dysfunctional telomeres by
modulation of telomeric DNA damage response RNAs.
PMID- 28406146
TI - Three-dimensional resistivity and switching between correlated electronic states
in 1T-TaS2.
AB - Recent demonstrations of controlled switching between different ordered
macroscopic states by impulsive electromagnetic perturbations in complex
materials have opened some fundamental questions on the mechanisms responsible
for such remarkable behavior. Here we experimentally address the question of
whether two-dimensional (2D) Mott physics can be responsible for unusual
switching between states of different electronic order in the layered
dichalcogenide 1T-TaS2, or it is a result of subtle inter-layer "orbitronic" re
ordering of its stacking structure. We report on in-plane (IP) and out-of-plane
(OP) resistance switching by current-pulse injection at low temperatures.
Elucidating the controversial theoretical predictions, we also report on
measurements of the anisotropy of the electrical resistivity below room
temperature. From the T-dependence of rho? and rho||, we surmise that the
resistivity is more consistent with collective motion than single particle
diffusive or band-like transport. The relaxation dynamics of the metastable state
for both IP and OP electron transport are seemingly governed by the same
mesoscopic quantum re-ordering process. We conclude that 1T-TaS2 shows resistance
switching arising from an interplay of both IP and OP correlations.
PMID- 28406147
TI - Transcriptome analyses of differential gene expression in the bursa of Fabricius
between Silky Fowl and White Leghorn.
AB - Hyperpigmentation in Silky Fowl (SF) results in aberrant immune cell development.
However, how melanocytes regulate B-cell proliferation in the bursa of Fabricius
(BF) is unclear. To resolve this conundrum, we collected BFs from three-week-old
SF and White Leghorn (WL) female chickens for RNA sequencing. The BF development
was relatively weaker in SF than in WL. The transcriptome analyses identified
4848 differentially expressed genes, 326 long noncoding RNAs (lncRNAs), and 67
microRNAs in the BF of SF. The genes associated with melanogenesis was
significantly higher, but that of the genes associated with the cytokine-cytokine
receptor interactions and JAK-STAT signalling pathway was significantly lower in
SF than in WL. Crucial biological processes, such as the receptor activity, cell
communication, and cellular responses to stimuli, were clustered in SF. The
predicted target lncRNAs genes were mainly associated with cell proliferation
pathways such as JAK-STAT, WNT, MAPK, and Notch signalling pathways. Except for
the above pathways, the target microRNA genes were related to the metabolism,
melanogenesis, autophagy, and NOD-like and Toll-like receptor signalling
pathways. The lncRNAs and microRNAs were predicted to regulate the JAK2, STAT3,
and IL-15 genes. Thus, B-cell development in the BF of SF might be regulated and
affected by noncoding RNAs.
PMID- 28406148
TI - Bladder cancer.
AB - Bladder cancer is a highly prevalent disease and is associated with substantial
morbidity, mortality and cost. Environmental or occupational exposures to
carcinogens, especially tobacco, are the main risk factors for bladder cancer.
Most bladder cancers are diagnosed after patients present with macroscopic
haematuria, and cases are confirmed after transurethral resection of bladder
tumour (TURBT), which also serves as the first stage of treatment. Bladder cancer
develops via two distinct pathways, giving rise to non-muscle-invasive papillary
tumours and non-papillary (solid) muscle-invasive tumours. The two subtypes have
unique pathological features and different molecular characteristics. Indeed, The
Cancer Genome Atlas project identified genetic drivers of muscle-invasive bladder
cancer (MIBC) as well as subtypes of MIBC with distinct characteristics and
therapeutic responses. For non-muscle-invasive bladder cancer (NMIBC),
intravesical therapies (primarily Bacillus Calmette-Guerin (BCG)) with
maintenance are the main treatments to prevent recurrence and progression after
initial TURBT; additional therapies are needed for those who do not respond to
BCG. For localized MIBC, optimizing care and reducing morbidity following
cystectomy are important goals. In metastatic disease, advances in our genetic
understanding of bladder cancer and in immunotherapy are being translated into
new therapies.
PMID- 28406150
TI - One-step assembly of 2H-1T MoS2:Cu/reduced graphene oxide nanosheets for highly
efficient hydrogen evolution.
AB - The transition metal dichagenides and their metallic 1T structure are attracting
contemporary attentions for applications in high-performance devices because
their peculiar optical and electrical properties. The single and few layers 1T
structure is generally obtained by mechanical or chemical exfoliation. This work
presents facile one-step synthesis of 2H-1T MoS2:Cu/reduced graphene oxide
nanosheets. The experiment results indicated that the MoS2 and MoS2:Cu prepared
by simple chemical solution reaction possessed 2H-1T structures. The reduced
graphene oxide (rGO) incorporation further induced the phase transition from 2H
MoS2 to 1T-MoS2 and morphology transition from granular/nanosheet to more
nanosheet. The 2H-1T structure and 2H -> 1T phase transition, together with the
Cu doping and interface effect between the MoS2 and rGO, remarkably enhanced the
conduction and photoconduction of the nanostructures. Thus, Cu doping and rGO
incorporation obviously enhanced the catalytic activity and its stability, making
the MoS2:Cu/rGO nanosheet a most active and stable catalyst for hydrogen
evolution. This work clearly indicates that the 1T-MoS2 nanosheets with high
catalytic activity for hydrogen evolution can be easily obtained by the facile
low temperature chemical method and induction of rGO.
PMID- 28406149
TI - Implantable batteryless device for on-demand and pulsatile insulin
administration.
AB - Many implantable systems have been designed for long-term, pulsatile delivery of
insulin, but the lifetime of these devices is limited by the need for battery
replacement and consequent replacement surgery. Here we propose a batteryless,
fully implantable insulin pump that can be actuated by a magnetic field. The pump
is prepared by simple-assembly of magnets and constituent units and comprises a
drug reservoir and actuator equipped with a plunger and barrel, each assembled
with a magnet. The plunger moves to noninvasively infuse insulin only when a
magnetic field is applied on the exterior surface of the body. Here we show that
the dose is easily controlled by varying the number of magnet applications. Also,
pump implantation in diabetic rats results in profiles of insulin concentration
and decreased blood glucose levels similar to those observed in rats treated with
conventional subcutaneous insulin injections.
PMID- 28406151
TI - Organic light emitting board for dynamic interactive display.
AB - Interactive displays involve the interfacing of a stimuli-responsive sensor with
a visual human-readable response. Here, we describe a polymeric
electroluminescence-based stimuli-responsive display method that simultaneously
detects external stimuli and visualizes the stimulant object. This organic light
emitting board is capable of both sensing and direct visualization of a variety
of conductive information. Simultaneous sensing and visualization of the
conductive substance is achieved when the conductive object is coupled with the
light emissive material layer on application of alternating current. A variety of
conductive materials can be detected regardless of their work functions, and thus
information written by a conductive pen is clearly visualized, as is a human
fingerprint with natural conductivity. Furthermore, we demonstrate that
integration of the organic light-emitting board with a fluidic channel readily
allows for dynamic monitoring of metallic liquid flow through the channel, which
may be suitable for biological detection and imaging applications.
PMID- 28406152
TI - Tunable transmission of quantum Hall edge channels with full degeneracy lifting
in split-gated graphene devices.
AB - Charge carriers in the quantum Hall regime propagate via one-dimensional
conducting channels that form along the edges of a two-dimensional electron gas.
Controlling their transmission through a gate-tunable constriction, also called
quantum point contact, is fundamental for many coherent transport experiments.
However, in graphene, tailoring a constriction with electrostatic gates remains
challenging due to the formation of p-n junctions below gate electrodes along
which electron and hole edge channels co-propagate and mix, short circuiting the
constriction. Here we show that this electron-hole mixing is drastically reduced
in high-mobility graphene van der Waals heterostructures thanks to the full
degeneracy lifting of the Landau levels, enabling quantum point contact operation
with full channel pinch-off. We demonstrate gate-tunable selective transmission
of integer and fractional quantum Hall edge channels through the quantum point
contact. This gate control of edge channels opens the door to quantum Hall
interferometry and electron quantum optics experiments in the integer and
fractional quantum Hall regimes of graphene.
PMID- 28406153
TI - Regio- and conformational isomerization critical to design of efficient thermally
activated delayed fluorescence emitters.
AB - Regio- and conformational isomerization are fundamental in chemistry, with
profound effects upon physical properties, however their role in excited state
properties is less developed. Here two regioisomers of bis(10H-phenothiazin-10
yl)dibenzo[b,d]thiophene-S,S-dioxide, a donor-acceptor-donor (D-A-D) thermally
activated delayed fluorescence (TADF) emitter, are studied. 2,8-bis(10H
phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide exhibits only one quasi
equatorial conformer on both donor sites, with charge-transfer (CT) emission
close to the local triplet state leading to efficient TADF via spin-vibronic
coupling. However, 3,7-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S
dioxide displays both a quasi-equatorial CT state and a higher-energy quasi-axial
CT state. No TADF is observed in the quasi-axial CT emission. These two CT states
link directly to the two folded conformers of phenothiazine. The presence of the
low-lying local triplet state of the axial conformer also means that this quasi
axial CT is an effective loss pathway both photophysically and in devices.
Importantly, donors or acceptors with more than one conformer have negative
repercussions for TADF in organic light-emitting diodes.
PMID- 28406154
TI - Pathways for balancing CO2 emissions and sinks.
AB - In December 2015 in Paris, leaders committed to achieve global, net
decarbonization of human activities before 2100. This achievement would halt and
even reverse anthropogenic climate change through the net removal of carbon from
the atmosphere. However, the Paris documents contain few specific prescriptions
for emissions mitigation, leaving various countries to pursue their own agendas.
In this analysis, we project energy and land-use emissions mitigation pathways
through 2100, subject to best-available parameterization of carbon-climate
feedbacks and interdependencies. We find that, barring unforeseen and
transformative technological advancement, anthropogenic emissions need to peak
within the next 10 years, to maintain realistic pathways to meeting the COP21
emissions and warming targets. Fossil fuel consumption will probably need to be
reduced below a quarter of primary energy supply by 2100 and the allowable
consumption rate drops even further if negative emissions technologies remain
technologically or economically unfeasible at the global scale.
PMID- 28406155
TI - Rapid population decline in migratory shorebirds relying on Yellow Sea tidal
mudflats as stopover sites.
AB - Migratory animals are threatened by human-induced global change. However, little
is known about how stopover habitat, essential for refuelling during migration,
affects the population dynamics of migratory species. Using 20 years of continent
wide citizen science data, we assess population trends of ten shorebird taxa that
refuel on Yellow Sea tidal mudflats, a threatened ecosystem that has shrunk by
>65% in recent decades. Seven of the taxa declined at rates of up to 8% per year.
Taxa with the greatest reliance on the Yellow Sea as a stopover site showed the
greatest declines, whereas those that stop primarily in other regions had slowly
declining or stable populations. Decline rate was unaffected by shared
evolutionary history among taxa and was not predicted by migration distance,
breeding range size, non-breeding location, generation time or body size. These
results suggest that changes in stopover habitat can severely limit migratory
populations.
PMID- 28406156
TI - Exploring the significance of morphological diversity for cerebellar granule cell
excitability.
AB - The relatively simple and compact morphology of cerebellar granule cells (CGCs)
has led to the view that heterogeneity in CGC shape has negligible impact upon
the integration of mossy fibre (MF) information. Following electrophysiological
recording, 3D models were constructed from high-resolution imaging data to
identify morphological features that could influence the coding of MF input
patterns by adult CGCs. Quantification of MF and CGC morphology provided evidence
that CGCs could be connected to the multiple rosettes that arise from a single MF
input. Predictions from our computational models propose that MF inputs could be
more densely encoded within the CGC layer than previous models suggest. Moreover,
those MF signals arriving onto the dendrite closest to the axon will generate
greater CGC excitation. However, the impact of this morphological variability on
MF input selectivity will be attenuated by high levels of CGC inhibition
providing further flexibility to the MF -> CGC pathway. These features could be
particularly important when considering the integration of multimodal MF sensory
input by individual CGCs.
PMID- 28406157
TI - Novel Heating-Induced Reversion during Crystallization of Al-based Glassy Alloys.
AB - Thermal stability and crystallization of three multicomponent glassy alloys,
Al86Y7Ni5Co1Fe0.5Pd0.5, Al85Y8Ni5Co1Fe0.5Pd0.5 and Al84Y9Ni4Co1.5Fe0.5Pd1, were
examined to assess the ability to form the mixture of amorphous (am) and fcc
aluminum (alpha-Al) phases. On heating, the glass transition into the supercooled
liquid is shown by the 85Al and 84Al glasses. The crystallization sequences are
[am] -> [am + alpha-Al] -> [alpha-Al + compounds] for the 86Al and 85Al alloys,
and [am] -> [am + alpha-Al + cubic AlxMy (M = Y, Ni, Co, Fe, Pd)] -> [am + alpha
Al] -> [alpha-Al + Al3Y + Al9(Co, Ni)2 + unknown phase] for the 84Al alloy. The
glass transition appears even for the 85Al alloy where the primary phase is alpha
Al. The heating-induced reversion from [am + alpha-Al + multicomponent AlxMy] to
[am + alpha-Al] for the 84Al alloy is abnormal, not previously observed in
crystallization of glassy alloys, and seems to originate from instability of the
metastable AlxMy compound, in which significant inhomogeneous strain is caused by
the mixture of solute elements. This novel reversion phenomenon is encouraging
for obtaining the [am + alpha-Al] mixture over a wide range of high temperature
effective for the formation of Al-based high-strength nanostructured bulk alloys
by warm working.
PMID- 28406158
TI - Burstiness and tie activation strategies in time-varying social networks.
AB - The recent developments in the field of social networks shifted the focus from
static to dynamical representations, calling for new methods for their analysis
and modelling. Observations in real social systems identified two main mechanisms
that play a primary role in networks' evolution and influence ongoing spreading
processes: the strategies individuals adopt when selecting between new or old
social ties, and the bursty nature of the social activity setting the pace of
these choices. We introduce a time-varying network model accounting both for ties
selection and burstiness and we analytically study its phase diagram. The
interplay of the two effects is non trivial and, interestingly, the effects of
burstiness might be suppressed in regimes where individuals exhibit a strong
preference towards previously activated ties. The results are tested against
numerical simulations and compared with two empirical datasets with very good
agreement. Consequently, the framework provides a principled method to classify
the temporal features of real networks, and thus yields new insights to elucidate
the effects of social dynamics on spreading processes.
PMID- 28406159
TI - Sensitivity and accuracy of high-throughput metabarcoding methods for early
detection of invasive fish species.
AB - High-throughput DNA metabarcoding has gained recognition as a potentially
powerful tool for biomonitoring, including early detection of aquatic invasive
species (AIS). DNA based techniques are advancing, but our understanding of the
limits to detection for metabarcoding complex samples is inadequate. For
detecting AIS at an early stage of invasion when the species is rare, accuracy at
low detection limits is key. To evaluate the utility of metabarcoding in future
fish community monitoring programs, we conducted several experiments to determine
the sensitivity and accuracy of routine metabarcoding methods. Experimental mixes
used larval fish tissue from multiple "common" species spiked with varying
proportions of tissue from an additional "rare" species. Pyrosequencing of
genetic marker, COI (cytochrome c oxidase subunit I) and subsequent sequence data
analysis provided experimental evidence of low-level detection of the target
"rare" species at biomass percentages as low as 0.02% of total sample biomass.
Limits to detection varied interspecifically and were susceptible to
amplification bias. Moreover, results showed some data processing methods can
skew sequence-based biodiversity measurements from corresponding relative biomass
abundances and increase false absences. We suggest caution in interpreting
presence/absence and relative abundance in larval fish assemblages until
metabarcoding methods are optimized for accuracy and precision.
PMID- 28406160
TI - Morphological Detection and Functional Assessment of Regenerated Nerve after
Neural Prosthesis with a PGLA Nerve Conduit.
AB - This study aimed to observe the morphological characteristics of a PGLA
[poly(glycolide-co-L-lactide)] nerve conduit and regenerated nerve bundle in the
human body using high-frequency ultrasound and examine functional recovery of the
regenerated nerve using functional magnetic resonance imaging (fMRI) after neural
prosthesis with a PGLA nerve conduit. Thirty-nine patients underwent high
frequency ultrasound, and one patient with superficial radial nerve injury (27-mm
defect) underwent fMRI at one, three, and six postoperative months. The fMRI
examination results were compared with sensory detection and high-frequency
ultrasound results during the same follow-up window period. The normal and
regenerated nerve bundles had similar ultrasonic imaging features. At one
postoperative month, fMRI displayed activeness of the normal cortex in the brain
region corresponding to the contralateral superficial radial nerve, while no
activeness was observed on the ipsilateral side. From three to six postoperative
months, fMRI revealed gradually increasing activeness in the brain region
corresponding to the ipsilateral superficial radial nerve, but the activation
area on the ipsilateral side was smaller than that on the contralateral side.
Combining morphological detection of the regenerated nerve using high-frequency
ultrasound and functional detection of the regenerated nerve using fMRI may be a
valuable method for evaluating repair of peripheral nerve injury.
PMID- 28406162
TI - Mucosal IgA and IFN-gamma+ CD8 T cell immunity are important in the efficacy of
live Salmonella enteria serovar Choleraesuis vaccines.
AB - Salmonellosis, a disease caused by non-typhoidal Salmonella strains which can be
transmitted from swine to humans, is one of the leading public health problems
around the world. Paratyphoid of swine is controlled by vaccinating swine with
Salmonella enterica serovar Choleraesuis (S. Choleraesuis) live vaccine strain
C500 in China. Although the vaccine has good prophylactic efficacy, the mechanism
of immunogenicity is unclear. Using a C500-derived paratyphoid thermo-stable live
vaccine (PTSL vaccine), we demonstrated that the PTSL vaccine induces strong
primary and memory immune responses in piglets. Mucosal IgA and IFN-gamma+/CD8+ T
cells induced by the PTSL vaccine play key roles in the protection of the host
from Salmonella infection. Our findings have important implications on the
development of new and improved vaccines against salmonellosis and using live
attenuated Salmonella as vaccine carriers.
PMID- 28406161
TI - Ribosomal background of the Bacillus cereus group thermotypes.
AB - In this study we reconstructed the architecture of Bacillus cereus sensu lato
population based on ribosomal proteins, and identified a link between the
ribosomal proteins' variants and thermal groups (thermotypes) of the bacilli. The
in silico phyloproteomic analysis of 55 ribosomal proteins (34 large and 21 small
subunit r-proteins) of 421 strains, representing 14 well-established or plausible
B. cereus sensu lato species, revealed several ribosomal clusters (r-clusters),
which in general were well correlated with the strains' affiliation to
phylogenetic/thermal groups I-VII. However, a conformity and possibly a thermal
characteristic of certain phylogenetic groups, e.g. the group IV, were not
supported by a distribution of the corresponding r-clusters, and consequently
neither by the analysis of cold-shock proteins (CSPs) nor by a content of heat
shock proteins (HSPs). Furthermore, a preference for isoleucine and serine over
valine and alanine in r-proteins along with a lack of HSP16.4 were recognized in
non-mesophilic thermotypes. In conclusion, we suggest that the observed
divergence in ribosomal proteins may be connected with an adaptation of B. cereus
sensu lato members to various thermal niches.
PMID- 28406163
TI - Actomyosin contractility provokes contact inhibition in E-cadherin-ligated
keratinocytes.
AB - Confluence-dependent inhibition of epithelial cell proliferation, termed contact
inhibition, is crucial for epithelial homeostasis and organ size control. Here we
report that among epithelial cells, keratinocytes, which compose the stratified
epithelium in the skin, possess a unique, actomyosin-dependent mechanism for
contact inhibition. We have observed that under actomyosin-inhibited conditions,
cell-cell contact itself through E-cadherin promotes proliferation of
keratinocytes. Actomyosin activity in confluent keratinocytes, however, inhibits
nuclear localization of beta-catenin and YAP, and causes attenuation of beta
catenin- and YAP-driven cell proliferation. Confluent keratinocytes develop E
cadherin-mediated punctate adhesion complexes, to which radial actin cables are
connected. Eliminating the actin-to-E-cadherin linkage by depleting alpha-catenin
increases proliferation of confluent keratinocytes. By contrast, enforced
activation of RhoA-regulated actomyosin or external application of pulling force
to ligated E-cadherin attenuates their proliferation, suggesting that tensile
stress at E-cadherin-mediated adhesion complexes inhibits proliferation of
confluent keratinocytes. Our results highlight actomyosin contractility as a
crucial factor that provokes confluence-dependent inhibition of keratinocyte
proliferation.
PMID- 28406164
TI - Spin-polarized Second Harmonic Generation from the Antiferromagnetic CaCoSO
Single Crystal.
AB - The spin-polarized second harmonic generation (SHG) of the recently synthesized
CaCoSO single crystal is performed based on the calculated electronic band
structure. The calculation reveals that the spin-up (?) channel of CaCoSO
possesses a direct energy gap (Gammav-Gammac) of about 2.187 eV, 1.187 eV (Kv-Kc)
for the spin-down (?) channel and an indirect gap (Gammav-Kc) of about 0.4 eV for
the spin-polarized CaCoSO single crystal. The linear optical properties obtained
reveal that the recently synthesized crystal exhibits considerable anisotropy
with negative uniaxial anisotropy and birefringence favor to enhance the SHG. We
have calculated the three non-zero tensor components of the SHG and found the is
the dominat component, one with a large SHG of about (d33 = 6.936 pm/V at lambda
= 1064 nm), the half value of KTiOPO4 (KTP). As the values of (?) < (?) < spin
polarized are related to the values of the energy gap of (?) 2.187 eV> (?) 1.187
eV> spin-polarized gap 0.4 eV; therefore, a smaller energy gap gives better SHG
performance. Furthermore, the microscopic first hyperpolarizability, betaijk, is
calculated.
PMID- 28406165
TI - Myostatin mediates abdominal aortic atherosclerosis progression by inducing
vascular smooth muscle cell dysfunction and monocyte recruitment.
AB - Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic
disorders and heart fibrosis. In this study we sought to verify whether Mstn is
also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn
expression was almost absent in normal vessels, became detectable in the media of
non-progressive lesions and increased with the severity of the damage. In
progressive atherosclerotic lesions, Mstn was present in the media, neointima,
plaque shoulder and in infiltrating macrophages. Mstn co-localized with alpha
smooth muscle actin (alpha-SMA) staining and with some CD45+ cells, indicating
Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was
tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation
and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate
and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn
acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin,
alpha-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn
induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate
that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs
and monocyte biology and sustains a chronic inflammatory milieu. These findings
propose to consider Mstn as a new playmaker in atherosclerosis progression.
PMID- 28406166
TI - Office-based simple frailty score and central blood pressure predict mild
cognitive impairment in an apparently healthy Japanese population: J-SHIPP study.
AB - Frailty is associated with cognitive impairment and can be used to identify
people at high risk for dementia. We developed a simple frailty (SF) score using
a combination of low hand grip strength (<32.5 kg in men, <19.5 kg in women), and
short one-leg standing time (<20 seconds). These can be easily measured in the
clinician's office when seeing patients. We investigated the possible association
between SF score and mild cognitive impairment (MCI) in a cross-sectional study
with 838 independent middle-aged to elderly participants (319 men, mean age
65.1years). In total, 118 participants were diagnosed with MCI. A SF score of 2
was significantly associated with the presence of MCI (odds ratio 4.6, 95%
confidence interval: 1.9-6.9, p = 0.0001) even after adjustment for age and sex.
Stepwise regression analyses showed that a SF score of 2 was associated with the
presence of MCI, independently of central pulse pressure and silent cerebral
infarcts. These findings indicate that the SF score is a useful frailty parameter
to predict MCI in an apparently independent population.
PMID- 28406167
TI - Persistence of a sugar-rejecting cockroach genotype under various dietary
regimes.
AB - Glucose-aversion is a heritable trait that evolved in a number of German
cockroach (Blattella germanica L.) populations in response to strong selection
with glucose-containing insecticide baits. However, in the absence of glucose
containing bait, glucose-averse (GA) cockroaches have lower performance than wild
type (WT) cockroaches in several fitness-determining traits. We allocated 48
caged populations initiated with homozygous GA and WT adults to four dietary
treatments consisting of either pure rodent chow, rodent chow mixed to yield a
content of either 20% glucose or 20% fructose, or a treatment consisting of
choice between the 20% glucose- and the 20% fructose-containing food. After 6
months we found significantly higher frequency of WT individuals in populations
restricted to the 20% glucose food, and after 12 months all dietary treatments
contained significantly more WT individuals than expected. In accompanying
experiments, we found lower survival and longer development time of GA nymphs
restricted to glucose-containing food. We furthermore found evidence for
assortative mating of females with males from their own genotype, with
significant differences within WT cockroaches. Our study shows experimental
evidence that within heterogeneous populations, WT German cockroaches will over
time prevail in abundance over GA individuals, even when glucose is not a dietary
component.
PMID- 28406168
TI - Staphylococcus sciuri bacteriophages double-convert for staphylokinase and
phospholipase, mediate interspecies plasmid transduction, and package mecA gene.
AB - Staphylococcus sciuri is a bacterial pathogen associated with infections in
animals and humans, and represents a reservoir for the mecA gene encoding
methicillin-resistance in staphylococci. No S. sciuri siphophages were known.
Here the identification and characterization of two temperate S. sciuri phages
from the Siphoviridae family designated phi575 and phi879 are presented. The
phages have icosahedral heads and flexible noncontractile tails that end with a
tail spike. The genomes of the phages are 42,160 and 41,448 bp long and encode 58
and 55 ORFs, respectively, arranged in functional modules. Their head-tail
morphogenesis modules are similar to those of Staphylococcus aureus phi13-like
serogroup F phages, suggesting their common evolutionary origin. The genome of
phage phi575 harbours genes for staphylokinase and phospholipase that might
enhance the virulence of the bacterial hosts. In addition both of the phages
package a homologue of the mecA gene, which is a requirement for its lateral
transfer. Phage phi879 transduces tetracycline and aminoglycoside pSTS7-like
resistance plasmids from its host to other S. sciuri strains and to S. aureus.
Furthermore, both of the phages efficiently adsorb to numerous staphylococcal
species, indicating that they may contribute to interspecies horizontal gene
transfer.
PMID- 28406169
TI - Single-molecule electrical contacts on silicon electrodes under ambient
conditions.
AB - The ultimate goal in molecular electronics is to use individual molecules as the
active electronic component of a real-world sturdy device. For this concept to
become reality, it will require the field of single-molecule electronics to shift
towards the semiconducting platform of the current microelectronics industry.
Here, we report silicon-based single-molecule contacts that are mechanically and
electrically stable under ambient conditions. The single-molecule contacts are
prepared on silicon electrodes using the scanning tunnelling microscopy break
junction approach using a top metallic probe. The molecular wires show remarkable
current-voltage reproducibility, as compared to an open silicon/nano-gap/metal
junction, with current rectification ratios exceeding 4,000 when a low-doped
silicon is used. The extension of the single-molecule junction approach to a
silicon substrate contributes to the next level of miniaturization of electronic
components and it is anticipated it will pave the way to a new class of robust
single-molecule circuits.
PMID- 28406170
TI - Identification of proteins involved in the anti-inflammatory properties of
Propionibacterium freudenreichii by means of a multi-strain study.
AB - Propionibacterium freudenreichii, a dairy starter, can reach a population of
almost 109 propionibacteria per gram in Swiss-type cheese at the time of
consumption. Also consumed as a probiotic, it displays strain-dependent anti
inflammatory properties mediated by surface proteins that induce IL-10 in
leukocytes. We selected 23 strains with varied anti-inflammatory potentials in
order to identify the protein(s) involved. After comparative genomic analysis, 12
of these strains were further analysed by surface proteomics, eight of them being
further submitted to transcriptomics. The omics data were then correlated to the
anti-inflammatory potential evaluated by IL-10 induction. This comparative omics
strategy highlighted candidate genes that were further subjected to gene
inactivation validation. This validation confirmed the contribution of surface
proteins, including SlpB and SlpE, two proteins with SLH domains known to mediate
non-covalent anchorage to the cell-wall. Interestingly, HsdM3, predicted as
cytoplasmic and involved in DNA modification, was shown to contribute to anti
inflammatory activity. Finally, we demonstrated that a single protein cannot
explain the anti-inflammatory properties of a strain. These properties therefore
result from different combinations of surface and cytoplasmic proteins, depending
on the strain. Our enhanced understanding of the molecular bases for
immunomodulation will enable the relevant screening for bacterial resources with
anti-inflammatory properties.
PMID- 28406171
TI - Optical Coherence Tomography Angiography to Estimate Retinal Blood Flow in Eyes
with Retinitis Pigmentosa.
AB - Ophthalmologists sometimes face difficulties in identifying the origin of visual
acuity (VA) loss in a retinitis pigmentosa (RP) patient, particularly before
cataract surgery: cataract or the retinal disease state. Therefore, it is
important to identify the significant factors correlating with VA. Nowadays,
retinal blood flow in superficial and deep layers can be estimated non-invasively
using optical coherence tomography angiography (OCTA). We estimated blood flow
per retinal layer by using OCTA; investigated the correlation between VA and
other parameters including blood flow and retinal thickness; and identified the
most associated factor with VA in patients with RP. OCTA images in 68 of
consecutive 110 Japanese RP patients were analysable (analysable RP group).
Thirty-two age- and axial length-matched healthy eyes (control group) were
studied. In the analysable RP group, the parafoveal flow density in superficial
and deep layers was 47.0 +/- 4.9% and 52.4 +/- 5.5%, respectively, which was
significantly lower than that in controls. Using multivariate analysis, we found
that the parafoveal flow density in the deep layer and superficial foveal
avascular area were the factors associated with VA. Non-invasive estimation of
retinal blood flow per retinal layer using OCTA is useful for predicting VA in RP
patients.
PMID- 28406172
TI - Anchored but not internalized: shape dependent endocytosis of nanodiamond.
AB - Nanoparticle-cell interactions begin with the cellular uptake of the
nanoparticles, a process that eventually determines their cellular fate. In the
present work, we show that the morphological features of nanodiamonds (NDs)
affect both the anchoring and internalization stages of their endocytosis. While
a prickly ND (with sharp edges/corners) has no trouble of anchoring onto the
plasma membrane, it suffers from difficult internalization afterwards. In
comparison, the internalization of a round ND (obtained by selective etching of
the prickly ND) is not limited by its lower anchoring amount and presents a much
higher endocytosis amount. Molecular dynamics simulation and continuum modelling
results suggest that the observed difference in the anchoring of round and
prickly NDs likely results from the reduced contact surface area with the cell
membrane of the former, while the energy penalty associated with membrane
curvature generation, which is lower for a round ND, may explain its higher
probability of the subsequent internalization.
PMID- 28406173
TI - Emergence of a coherent and cohesive swarm based on mutual anticipation.
AB - Collective behavior emerging out of self-organization is one of the most striking
properties of an animal group. Typically, it is hypothesized that each individual
in an animal group tends to align its direction of motion with those of its
neighbors. Most previous models for collective behavior assume an explicit
alignment rule, by which an agent matches its velocity with that of neighbors in
a certain neighborhood, to reproduce a collective order pattern by simple
interactions. Recent empirical studies, however, suggest that there is no
evidence for explicit matching of velocity, and that collective polarization
arises from interactions other than those that follow the explicit alignment
rule. We here propose a new lattice-based computational model that does not
incorporate the explicit alignment rule but is based instead on mutual
anticipation and asynchronous updating. Moreover, we show that this model can
realize densely collective motion with high polarity. Furthermore, we focus on
the behavior of a pair of individuals, and find that the turning response is
drastically changed depending on the distance between two individuals rather than
the relative heading, and is consistent with the empirical observations.
Therefore, the present results suggest that our approach provides an alternative
model for collective behavior.
PMID- 28406174
TI - Complete fold annotation of the human proteome using a novel structural feature
space.
AB - Recognition of protein structural fold is the starting point for many structure
prediction tools and protein function inference. Fold prediction is
computationally demanding and recognizing novel folds is difficult such that the
majority of proteins have not been annotated for fold classification. Here we
describe a new machine learning approach using a novel feature space that can be
used for accurate recognition of all 1,221 currently known folds and inference of
unknown novel folds. We show that our method achieves better than 94% accuracy
even when many folds have only one training example. We demonstrate the utility
of this method by predicting the folds of 34,330 human protein domains and
showing that these predictions can yield useful insights into potential
biological function, such as prediction of RNA-binding ability. Our method can be
applied to de novo fold prediction of entire proteomes and identify candidate
novel fold families.
PMID- 28406175
TI - Nkx2-5 and Sarcospan genetically interact in the development of the muscular
ventricular septum of the heart.
AB - The muscular ventricular septum separates the flow of oxygenated and de
oxygenated blood in air-breathing vertebrates. Defects within it, termed muscular
ventricular septal defects (VSDs), are common, yet less is known about how they
arise than rarer heart defects. Mutations of the cardiac transcription factor
NKX2-5 cause cardiac malformations, including muscular VSDs. We describe here a
genetic interaction between Nkx2-5 and Sarcospan (Sspn) that affects the risk of
muscular VSD in mice. Sspn encodes a protein in the dystrophin-glycoprotein
complex. Sspn knockout (SspnKO) mice do not have heart defects, but Nkx2-5+/
/SspnKO mutants have a higher incidence of muscular VSD than Nkx2-5+/- mice.
Myofibers in the ventricular septum follow a stereotypical pattern that is
disrupted around a muscular VSD. Subendocardial myofibers normally run in
parallel along the left ventricular outflow tract, but in the Nkx2-5+/-/SspnKO
mutant they commonly deviate into the septum even in the absence of a muscular
VSD. Thus, Nkx2-5 and Sspn act in a pathway that affects the alignment of
myofibers during the development of the ventricular septum. The malalignment may
be a consequence of a defect in the coalescence of trabeculae into the developing
ventricular septum, which has been hypothesized to be the mechanistic basis of
muscular VSDs.
PMID- 28406177
TI - High-Q photonic resonators and electro-optic coupling using silicon-on-lithium
niobate.
AB - Future quantum networks, in which superconducting quantum processors are
connected via optical links, will require microwave-to-optical photon converters
that preserve entanglement. A doubly-resonant electro-optic modulator (EOM) is a
promising platform to realize this conversion. Here, we present our progress
towards building such a modulator by demonstrating the optically-resonant half of
the device. We demonstrate high quality (Q) factor ring, disk and photonic
crystal resonators using a hybrid silicon-on-lithium-niobate material system.
Optical Q factors up to 730,000 are achieved, corresponding to propagation loss
of 0.8 dB/cm. We also use the electro-optic effect to modulate the resonance
frequency of a photonic crystal cavity, achieving a electro-optic modulation
coefficient between 1 and 2 pm/V. In addition to quantum technology, we expect
that our results will be useful both in traditional silicon photonics
applications and in high-sensitivity acousto-optic devices.
PMID- 28406176
TI - Male alliance behaviour and mating access varies with habitat in a dolphin social
network.
AB - Within-species variation in social structure has attracted interest recently
because of the potential to explore phenotypic plasticity and, specifically, how
demographic and ecological variation influence social structure. Populations of
bottlenose dolphins (Tursiops spp.) vary in male alliance formation, from no
alliances to simple pairs to, in Shark Bay, Western Australia, the most complex
nested alliances known outside of humans. Examination of ecological contributions
to this variation is complicated by differences among populations in other
potentially explanatory traits, such as phylogenetic distance, as well as female
reproductive schedules, sexual size dimorphism, and body size. Here, we report
our discovery of systematic spatial variation in alliance structure, seasonal
movements and access to mates within a single continuous social network in the
Shark Bay population. Participation in male trios (versus pairs), the sizes of
seasonal range shifts and consortship rates all decrease from north to south
along the 50 km length of the study area. The southern habitat, characterised by
shallow banks and channels, may be marginal relative to the open northern
habitat. The discovery of variation in alliance behaviour along a spatial axis
within a single population is unprecedented and demonstrates that alliance
complexity has an ecological component.
PMID- 28406178
TI - Prediction of regional functional impairment following experimental stroke via
connectome analysis.
AB - Recent advances in functional connectivity suggest that shared neuronal
activation patterns define brain networks linking anatomically separate brain
regions. We sought to investigate how cortical stroke disrupts multiple brain
regions in processing spatial information. We conducted a connectome
investigation at the mesoscale-level using the neuroVIISAS-framework, enabling
the analysis of directed and weighted connectivity in bilateral hemispheres of
cortical and subcortical brain regions. We found that spatial-exploration induced
brain activation mapped by Fos, a proxy of neuronal activity, was differentially
affected by stroke in a region-specific manner. The extent of hypoactivation
following spatial exploration is inversely correlated with the spatial distance
between the region of interest and region damaged by stroke, in particular within
the parietal association and the primary somatosensory cortex, suggesting that
the closer a region is to a stroke lesion, the more it would be affected during
functional activation. Connectome modelling with 43 network parameters failed to
reliably predict regions of hypoactivation in stroke rats exploring a novel
environment, despite a modest correlation found for the centrality and hubness
parameters in the home-caged animals. Further investigation in the inhibitory
versus excitatory neuronal networks and microcircuit connectivity is warranted to
improve the accuracy of predictability in post-stroke functional impairment.
PMID- 28406179
TI - Genetic visualization of protein interactions harnessing liquid phase
transitions.
AB - Protein-protein interactions (PPIs) are essential components of cellular
function. Current fluorescence-based technologies to measure PPIs have limited
dynamic range and quantitative reproducibility. Here, we describe a genetically
encoded PPI visualization system that harnesses the dynamics of condensed liquid
phase transitions to analyze protein interactions in living cells. The
fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners
triggered a rapid concatenation/oligomerization process that drove the
condensation of liquid-phase droplets for real-time analysis of the interaction
with unlimited dynamic range in the fluorescence signal. Proof-of-principle
studies revealed novel insights on the live cell dynamics of XIAP-Smac and ERK2
dimer interactions. A photoconvertible variant allowed time-resolved optical
highlighting for PPI kinetic analysis. Our system, called Fluoppi, demonstrates
the unique signal amplification properties of liquid-phase condensation to detect
PPIs. The findings introduce a general method for discovery of novel PPIs and
modulators of established PPIs.
PMID- 28406180
TI - DNA methylation landscape of ocular tissue relative to matched peripheral blood.
AB - Epigenetic variation is implicated in a range of non-communicable diseases,
including those of the eye. However, investigating the role of epigenetic
variation in central tissues, such as eye or brain, remains problematic and
peripheral tissues are often used as surrogates. In this study, matched human
blood and eye tissue (n = 8) were obtained post-mortem and DNA methylation
profiling performed on blood, neurosensory retina, retinal pigment epithelium
(RPE)/choroid and optic nerve tissue using the Illumina Infinium
HumanMethylation450 platform. Unsupervised clustering and principal components
analysis revealed tissue of origin as the main driver of methylation variation.
Despite this, there was a strong correlation of methylation profiles between
tissues with >255,000 CpG sites found to have similar methylation levels. An
additional ~16,000 show similarity across ocular tissues only. A small proportion
of probes showing inter-individual variation in blood co-varied with eye tissues
within individuals, however much of this variation may be genetically driven. An
improved understanding of the epigenetic landscape of the eye will have important
implications for understanding eye disease. Despite a generally high correlation
irrespective of origin, tissue type is the major driver of methylation variation,
with only limited covariation between blood and any specific ocular tissue.
PMID- 28406182
TI - Valvular disease: Transcatheter repair of severe tricuspid regurgitation.
PMID- 28406181
TI - Local inhibition of microtubule dynamics by dynein is required for neuronal cargo
distribution.
AB - Abnormal axonal transport is associated with neuronal disease. We identified a
role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo
distribution. Surprisingly, this does not involve dynein's role as a retrograde
motor in cargo transport, hinging instead on its ability to inhibit microtubule
(MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional
significance of this property are not well understood. In disease-mimicking dhc-1
alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in
the formation of aberrant MT loops. These unstable MTs act as cargo traps,
leading to ectopic accumulations of cargo and reduced availability of cargo at
normal locations. Our data suggest that an anchored dynein pool interacts with
plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These
results identify functional significance for neuronal MT stability and suggest a
mechanism for cellular dysfunction in dynein-linked disease.
PMID- 28406183
TI - Interventional cardiology: Increased risk of stent thrombosis with bioresorbable
scaffolds.
PMID- 28406185
TI - Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular
reprogramming associated with key regulators of cytoskeleton-extracellular matrix
remodelling.
AB - Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem
cells. It is a well-established marker for cancer stem cell (CSC) in
malignancies. Recently, using a loss of function studies, we have demonstrated
key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in
vitro and in vivo models of ovarian cancer. In an effort to understand the
regulatory role of Oct4A in tumor biology, we employed the use of an ovarian
cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass
spectrometry (MS)-based proteomic analysis to investigate novel biological
targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor
xenografts). Based on significant differential expression, pathway and protein
network analyses, and comprehensive literature search we identified key proteins
involved with biologically relevant functions of Oct4A in tumor biology. Across
all preparations of HEY Oct4A KD samples significant alterations in protein
networks associated with cytoskeleton, extracellular matrix (ECM), proliferation,
adhesion, metabolism, epithelial-mesenchymal transition (EMT), cancer stem cells
(CSCs) and drug resistance was observed. This comprehensive proteomics study for
the first time presents the Oct4A associated proteome and expands our
understanding on the biological role of this stem cell regulator in carcinomas.
PMID- 28406186
TI - Renin-Angiotensin System Inhibitor is Associated with Lower Risk of Ensuing
Chronic Kidney Disease after Functional Recovery from Acute Kidney Injury.
AB - Acute kidney injury (AKI) is an independent risk factor for ensuing chronic
kidney disease (CKD). Animal studies have demonstrated that renin-angiotensin
system (RAS) inhibitor can reduce ensuing CKD after functional recovery from AKI.
Here we study the association between ensuing CKD and use of RAS inhibitor
including angiotensin converting enzyme inhibitor or angiotensin II type 1a
receptor blocker starting after renal functional recovery in our prospectively
collected observational AKI cohort. Adult patients who had cardiac surgery
associated AKI (CSA-AKI) are studied. Patients with CKD, unrecovered AKI, and use
of RAS inhibitor before surgery are excluded. Among 587 eligible patients, 94
patients are users of RAS inhibitor which is started and continued after complete
renal recovery during median follow-up period of 2.99 years. The users of RAS
inhibitor show significantly lower rate of ensuing CKD (users vs. non-users,
26.6% vs. 42.2%) and longer median CKD-free survival time (users vs. non-users,
1079 days vs. 520 days). Multivariate Cox regression analyses further demonstrate
that use of RAS inhibitor is independently associated with lower risk of ensuing
CKD (hazard ratio = 0.46, P < 0.001). We conclude that use of RAS inhibitor in
CSA-AKI patients after renal functional recovery is associated with lower risk of
ensuing CKD development.
PMID- 28406189
TI - Legal approaches regarding health-care decisions involving minors: implications
for next-generation sequencing.
PMID- 28406187
TI - Cell-matrix adhesion and cell-cell adhesion differentially control basal myosin
oscillation and Drosophila egg chamber elongation.
AB - Pulsatile actomyosin contractility, important in tissue morphogenesis, has been
studied mainly in apical but less in basal domains. Basal myosin oscillation
underlying egg chamber elongation is regulated by both cell-matrix and cell-cell
adhesions. However, the mechanism by which these two adhesions govern basal
myosin oscillation and tissue elongation is unknown. Here we demonstrate that
cell-matrix adhesion positively regulates basal junctional Rho1 activity and
medio-basal ROCK and myosin activities, thus strongly controlling tissue
elongation. Differently, cell-cell adhesion governs basal myosin oscillation
through controlling medio-basal distributions of both ROCK and myosin signals,
which are related to the spatial limitations of cell-matrix adhesion and stress
fibres. Contrary to cell-matrix adhesion, cell-cell adhesion weakly affects
tissue elongation. In vivo optogenetic protein inhibition spatiotemporally
confirms the different effects of these two adhesions on basal myosin
oscillation. This study highlights the activity and distribution controls of
basal myosin contractility mediated by cell-matrix and cell-cell adhesions,
respectively, during tissue morphogenesis.
PMID- 28406184
TI - Monocytes and macrophages in abdominal aortic aneurysm.
AB - Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with
high morbidity, and high mortality in the event of aortic rupture. Major advances
in open surgical and endovascular repair of AAA have been achieved during the
past 2 decades. However, drug-based therapies are still lacking, highlighting a
real need for better understanding of the molecular and cellular mechanisms
involved in AAA formation and progression. The main pathological features of AAA
include extracellular matrix remodelling associated with degeneration and loss of
vascular smooth muscle cells and accumulation and activation of inflammatory
cells. The inflammatory process has a crucial role in AAA and substantially
influences many determinants of aortic wall remodelling. In this Review, we focus
specifically on the involvement of monocytes and macrophages, summarizing current
knowledge on the roles, origin, and functions of these cells in AAA development
and its complications. Furthermore, we show and propose that distinct monocyte
and macrophage subsets have critical and differential roles in initiation,
progression, and healing of the aneurysmal process. On the basis of experimental
and clinical studies, we review potential translational applications to detect,
assess, and image macrophage subsets in AAA, and discuss the relevance of these
applications for clinical practice.
PMID- 28406192
TI - Inkjet printing-based volumetric display projecting multiple full-colour 2D
patterns.
AB - In this study, a method to construct a full-colour volumetric display is
presented using a commercially available inkjet printer. Photoreactive
luminescence materials are minutely and automatically printed as the volume
elements, and volumetric displays are constructed with high resolution using easy
to-fabricate means that exploit inkjet printing technologies. The results
experimentally demonstrate the first prototype of an inkjet printing-based
volumetric display composed of multiple layers of transparent films that yield a
full-colour three-dimensional (3D) image. Moreover, we propose a design algorithm
with 3D structures that provide multiple different 2D full-colour patterns when
viewed from different directions and experimentally demonstrate prototypes. It is
considered that these types of 3D volumetric structures and their fabrication
methods based on widely deployed existing printing technologies can be utilised
as novel information display devices and systems, including digital signage,
media art, entertainment and security.
PMID- 28406191
TI - Synthesis and Biological Evaluation of 2-Methyl-4,5-Disubstituted Oxazoles as a
Novel Class of Highly Potent Antitubulin Agents.
AB - Antimitotic agents that interfere with microtubule formation are one of the major
classes of cytotoxic drugs for cancer treatment. Multiple 2-methyl-4-(3',4',5'
trimethoxyphenyl)-5-substituted oxazoles and their related 4-substituted-5
(3',4',5'-trimethoxyphenyl) regioisomeric derivatives designed as cis-constrained
combretastatin A-4 (CA-4) analogues were synthesized and evaluated for their
antiproliferative activity in vitro against a panel of cancer cell lines and, for
selected highly active compounds, interaction with tubulin, cell cycle effects
and in vivo potency. Both these series of compounds were characterized by the
presence of a common 3',4',5'-trimethoxyphenyl ring at either the C-4 or C-5
position of the 2-methyloxazole ring. Compounds 4g and 4i, bearing a m-fluoro-p
methoxyphenyl or p-ethoxyphenyl moiety at the 5-position of 2-methyloxazole
nucleus, respectively, exhibited the greatest antiproliferative activity, with
IC50 values of 0.35-4.6 nM (4g) and 0.5-20.2 nM (4i), which are similar to those
obtained with CA-4. These compounds bound to the colchicine site of tubulin and
inhibited tubulin polymerization at submicromolar concentrations. Furthermore, 4i
strongly induced apoptosis that follows the mitochondrial pathway. In vivo, 4i in
a mouse syngeneic model demonstrated high antitumor activity which significantly
reduced the tumor mass at doses ten times lower than that required for CA-4P,
suggesting that 4i warrants further evaluation as a potential anticancer drug.
PMID- 28406193
TI - Breathing modes of Kolumbo submarine volcano (Santorini, Greece).
AB - Submarine volcanoes, such as Kolumbo (Santorini, Greece) are natural laboratories
for fostering multidisciplinary studies. Their investigation requires the most
innovative marine technology together with advanced data analysis. Conductivity
and temperature of seawater were recorded directly above Kolumbo's hydrothermal
vent system. The respective time series have been analyzed in terms of non
equilibrium techniques. The energy dissipation of the volcanic activity is
monitored by the temperature variations of seawater. The venting dynamics of
chemical products is monitored by water conductivity. The analysis of the time
series in terms of stochastic processes delivers scaling exponents with turning
points between consecutive regimes for both conductivity and temperature. Changes
of conductivity are shown to behave as a universal multifractal and their
variance is subdiffusive as the scaling exponents indicate. Temperature is
constant over volcanic rest periods and a universal multifractal behavior
describes its changes in line with a subdiffusive character otherwise. The
universal multifractal description illustrates the presence of non-conservative
conductivity and temperature fields showing that the system never retains a real
equilibrium state. The existence of a repeated pattern of the combined effect of
both seawater and volcanic activity is predicted. The findings can shed light on
the dynamics of chemical products emitted from the vents and point to the
presence of underlying mechanisms that govern potentially hazardous, underwater
volcanic environments.
PMID- 28406195
TI - Artificial intelligence: Outsmart supply dips in renewable energy.
PMID- 28406194
TI - Influenza C in Lancaster, UK, in the winter of 2014-2015.
AB - Influenza C is not included in the annual seasonal influenza vaccine, and has
historically been regarded as a minor respiratory pathogen. However, recent work
has highlighted its potential role as a cause of pneumonia in infants. We
performed nasopharyngeal or nasal swabbing and/or serum sampling (n = 148) in
Lancaster, UK, over the winter of 2014-2015. Using enzyme-linked immunosorbent
assay (ELISA), we obtain seropositivity of 77%. By contrast, only 2 individuals,
both asymptomatic adults, were influenza C-positive by polymerase chain reaction
(PCR). Deep sequencing of nasopharyngeal samples produced partial sequences for 4
genome segments in one of these patients. Bayesian phylogenetic analysis
demonstrated that the influenza C genome from this individual is evolutionarily
distant to those sampled in recent years and represents a novel genome
constellation, indicating that it may be a product of a decades-old reassortment
event. Although we find no evidence that influenza C was a significant
respiratory pathogen during the winter of 2014-2015 in Lancaster, we confirm
previous observations of seropositivity in the majority of the population. (170
words).
PMID- 28406196
TI - Training: Plug gap in essential bioinformatics skills.
PMID- 28406197
TI - Human studies: Reforms overdue for ethical reviewing.
PMID- 28406199
TI - Biomedicine: Human genes lost and their functions found.
PMID- 28406200
TI - Developmental biology: How the lizard gets its speckled scales.
PMID- 28406198
TI - Topological defects in epithelia govern cell death and extrusion.
AB - Epithelial tissues (epithelia) remove excess cells through extrusion, preventing
the accumulation of unnecessary or pathological cells. The extrusion process can
be triggered by apoptotic signalling, oncogenic transformation and overcrowding
of cells. Despite the important linkage of cell extrusion to developmental,
homeostatic and pathological processes such as cancer metastasis, its underlying
mechanism and connections to the intrinsic mechanics of the epithelium are
largely unexplored. We approach this problem by modelling the epithelium as an
active nematic liquid crystal (that has a long range directional order), and
comparing numerical simulations to strain rate and stress measurements within
monolayers of MDCK (Madin Darby canine kidney) cells. Here we show that apoptotic
cell extrusion is provoked by singularities in cell alignments in the form of
comet-shaped topological defects. We find a universal correlation between
extrusion sites and positions of nematic defects in the cell orientation field in
different epithelium types. The results confirm the active nematic nature of
epithelia, and demonstrate that defect-induced isotropic stresses are the primary
precursors of mechanotransductive responses in cells, including YAP (Yes
associated protein) transcription factor activity, caspase-3-mediated cell death,
and extrusions. Importantly, the defect-driven extrusion mechanism depends on
intercellular junctions, because the weakening of cell-cell interactions in an
alpha-catenin knockdown monolayer reduces the defect size and increases both the
number of defects and extrusion rates, as is also predicted by our model. We
further demonstrate the ability to control extrusion hotspots by geometrically
inducing defects through microcontact printing of patterned monolayers. On the
basis of these results, we propose a mechanism for apoptotic cell extrusion:
spontaneously formed topological defects in epithelia govern cell fate. This will
be important in predicting extrusion hotspots and dynamics in vivo, with
potential applications to tissue regeneration and the suppression of metastasis.
Moreover, we anticipate that the analogy between the epithelium and active
nematic liquid crystals will trigger further investigations of the link between
cellular processes and the material properties of epithelia.
PMID- 28406202
TI - Finding pathways to national-scale land-sector sustainability.
AB - The 17 Sustainable Development Goals (SDGs) and 169 targets under Agenda 2030 of
the United Nations map a coherent global sustainability ambition at a level of
detail general enough to garner consensus amongst nations. However, achieving the
global agenda will depend heavily on successful national-scale implementation,
which requires the development of effective science-driven targets tailored to
specific national contexts and supported by strong national governance. Here we
assess the feasibility of achieving multiple SDG targets at the national scale
for the Australian land-sector. We scaled targets to three levels of ambition and
two timeframes, then quantitatively explored the option space for target
achievement under 648 plausible future environmental, socio-economic,
technological and policy pathways using the Land-Use Trade-Offs (LUTO) integrated
land systems model. We show that target achievement is very sensitive to global
efforts to abate emissions, domestic land-use policy, productivity growth rate,
and land-use change adoption behaviour and capacity constraints. Weaker target
setting ambition resulted in higher achievement but poorer sustainability
outcomes. Accelerating land-use dynamics after 2030 changed the targets achieved
by 2050, warranting a longer-term view and greater flexibility in sustainability
implementation. Simultaneous achievement of multiple targets is rare owing to the
complexity of sustainability target implementation and the pervasive trade-offs
in resource-constrained land systems. Given that hard choices are needed, the
land-sector must first address the essential food/fibre production, biodiversity
and land degradation components of sustainability via specific policy pathways.
It may also contribute to emissions abatement, water and energy targets by
capitalizing on co-benefits. However, achieving targets relevant to the land
sector will also require substantial contributions from other sectors such as
clean energy, food systems and water resource management. Nations require
globally coordinated, national-scale, comprehensive, integrated, multi-sectoral
analyses to support national target-setting that prioritizes efficient and
effective sustainability interventions across societies, economies and
environments.
PMID- 28406205
TI - George Andrew Olah (1927-2017).
PMID- 28406206
TI - A living mesoscopic cellular automaton made of skin scales.
AB - In vertebrates, skin colour patterns emerge from nonlinear dynamical microscopic
systems of cell interactions. Here we show that in ocellated lizards a quasi
hexagonal lattice of skin scales, rather than individual chromatophore cells,
establishes a green and black labyrinthine pattern of skin colour. We analysed
time series of lizard scale colour dynamics over four years of their development
and demonstrate that this pattern is produced by a cellular automaton (a grid of
elements whose states are iterated according to a set of rules based on the
states of neighbouring elements) that dynamically computes the colour states of
individual mesoscopic skin scales to produce the corresponding macroscopic colour
pattern. Using numerical simulations and mathematical derivation, we identify how
a discrete von Neumann cellular automaton emerges from a continuous Turing
reaction-diffusion system. Skin thickness variation generated by three
dimensional morphogenesis of skin scales causes the underlying reaction-diffusion
dynamics to separate into microscopic and mesoscopic spatial scales, the latter
generating a cellular automaton. Our study indicates that cellular automata are
not merely abstract computational systems, but can directly correspond to
processes generated by biological evolution.
PMID- 28406208
TI - Biological physics: Liquid crystals in living tissue.
PMID- 28406209
TI - Mechanobiology: A measure of molecular muscle.
PMID- 28406211
TI - 50 &100 Years Ago.
PMID- 28406210
TI - Japan: Unjustified killing of badgers in Kyushu.
PMID- 28406213
TI - Cutting collaborations will not put 'America first'.
PMID- 28406214
TI - 'Young poo' makes aged fish live longer.
PMID- 28406215
TI - Make perovskite solar cells stable.
PMID- 28406216
TI - Nature supports the March for Science.
PMID- 28406212
TI - Human knockouts and phenotypic analysis in a cohort with a high rate of
consanguinity.
AB - A major goal of biomedicine is to understand the function of every gene in the
human genome. Loss-of-function mutations can disrupt both copies of a given gene
in humans and phenotypic analysis of such 'human knockouts' can provide insight
into gene function. Consanguineous unions are more likely to result in offspring
carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates
are notably high. Here we sequence the protein-coding regions of 10,503 adult
participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS),
designed to understand the determinants of cardiometabolic diseases in
individuals from South Asia. We identified individuals carrying homozygous
predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis
involving more than 200 biochemical and disease traits. We enumerated 49,138 rare
(<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated
to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF
mutations at PLA2G7 was associated with absent enzymatic activity of soluble
lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma
interleukin-8 concentrations; at TREH, with lower concentrations of apoB
containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly
reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators
of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been
shown to protect against coronary heart disease; we identified APOC3 homozygous
pLoF carriers in our cohort. We recruited these human knockouts and challenged
them with an oral fat load. Compared with family members lacking the mutation,
individuals with APOC3 knocked out displayed marked blunting of the usual post
prandial rise in plasma triglycerides. Overall, these observations provide a
roadmap for a 'human knockout project', a systematic effort to understand the
phenotypic consequences of complete disruption of genes in humans.
PMID- 28406217
TI - Mobile-phone signals bolster street-level rain forecasts.
PMID- 28406218
TI - Immigration crackdowns damage health - even for unborn children.
PMID- 28406219
TI - Saturn spacecraft begins science swan-song.
PMID- 28406220
TI - Corrections.
PMID- 28406221
TI - The 100-year-old challenge to Darwin that is still making waves in research.
PMID- 28406222
TI - Hungary's protests, coral bleaching and a neutrino anomaly.
PMID- 28406224
TI - Muons' big moment could fuel new physics.
PMID- 28406223
TI - Natural-history collections face fight for survival.
PMID- 28406225
TI - Antarctica's sleeping ice giant could wake soon.
PMID- 28406226
TI - Fast optoelectric printing of plasmonic nanoparticles into tailored circuits.
AB - Plasmonic nanoparticles are able to control light at nanometre-scale by coupling
electromagnetic fields to the oscillations of free electrons in metals.
Deposition of such nanoparticles onto substrates with tailored patterns is
essential, for example, in fabricating plasmonic structures for enhanced sensing.
This work presents an innovative micro-patterning technique, based on optoelectic
printing, for fast and straightforward fabrication of curve-shaped circuits of
plasmonic nanoparticles deposited onto a transparent electrode often used in
optoelectronics, liquid crystal displays, touch screens, etc. We experimentally
demonstrate that this kind of plasmonic structure, printed by using silver
nanoparticles of 40 nm, works as a plasmonic enhanced optical device allowing for
polarized-color-tunable light scattering in the visible. These findings have
potential applications in biosensing and fabrication of future optoelectronic
devices combining the benefits of plasmonic sensing and the functionality of
transparent electrodes.
PMID- 28406227
TI - 50-nm-resolution full-field X-ray microscope without chromatic aberration using
total-reflection imaging mirrors.
AB - X-ray spectromicroscopy with a full-field imaging technique is a powerful method
for chemical analysis of heterogeneous complex materials with a nano-scale
spatial resolution. For imaging optics, an X-ray reflective optical system has
excellent capabilities with highly efficient, achromatic, and long-working
distance properties. An advanced Kirkpatrick-Baez geometry that combines four
independent mirrors with elliptic and hyperbolic shapes in both horizontal and
vertical directions was developed for this purpose, although the complexity of
the system has a limited applicable range. Here, we present an optical system
consisting of two monolithic imaging mirrors. Elliptic and hyperbolic shapes were
formed on a single substrate to achieve both high resolution and sufficient
stability. The mirrors were finished with a ~1-nm shape accuracy using elastic
emission machining. The performance was tested at SPring-8 with a photon energy
of approximately 10 keV. We could clearly resolve 50-nm features in a Siemens
star without chromatic aberration and with high stability over 20 h. We applied
this system to X-ray absorption fine structure spectromicroscopy and identified
elements and chemical states in specimens of zinc and tungsten micron-size
particles.
PMID- 28406228
TI - Electrokinetic instability in microchannel ferrofluid/water co-flows.
AB - Electrokinetic instability refers to unstable electric field-driven disturbance
to fluid flows, which can be harnessed to promote mixing for various
electrokinetic microfluidic applications. This work presents a combined numerical
and experimental study of electrokinetic ferrofluid/water co-flows in
microchannels of various depths. Instability waves are observed at the ferrofluid
and water interface when the applied DC electric field is beyond a threshold
value. They are generated by the electric body force that acts on the free charge
induced by the mismatch of ferrofluid and water electric conductivities. A
nonlinear depth-averaged numerical model is developed to understand and simulate
the interfacial electrokinetic behaviors. It considers the top and bottom channel
walls' stabilizing effects on electrokinetic flow through the depth averaging of
three-dimensional transport equations in a second-order asymptotic analysis. This
model is found accurate to predict both the observed electrokinetic instability
patterns and the measured threshold electric fields for ferrofluids of different
concentrations in shallow microchannels.
PMID- 28406229
TI - The role of focal adhesion anchoring domains of CAS in mechanotransduction.
AB - CAS is a docking protein, which was shown to act as a mechanosensor in focal
adhesions. The unique assembly of structural domains in CAS is important for its
function as a mechanosensor. The tension within focal adhesions is transmitted to
a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH
domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic
models of the stretching biosensor propose equal roles for both anchoring
domains. Using deletion mutants and domain replacements, we have analyzed the
relative importance of the focal adhesion anchoring domains on CAS localization
and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction.
We confirmed the predicted prerequisite of the focal adhesion targeting for CAS
dependent mechanosensing and unraveled the critical importance of CAS SH3 domain
in mechanosensing. We further show that CAS localizes to the force transduction
layer of focal adhesions and that mechanical stress stabilizes CAS in focal
adhesions.
PMID- 28406231
TI - Environmentally friendly synthesis of CeO2 nanoparticles for the catalytic
oxidation of benzyl alcohol to benzaldehyde and selective detection of nitrite.
AB - Cerium oxide nanoparticles (CeO2 NPs) are favorable in nanotechnology based on
some remarkable properties. In this study, the crystalline CeO2 NPs are
successfully prepared by an efficient microwave combustion (MCM) and conventional
route sol-gel (CRSGM) methods. The structural morphology of the as-prepared CeO2
NPs was investigated by various spectroscopic and analytical techniques.
Moreover, the XRD pattern confirmed the formation of CeO2 NPs as a face centered
cubic structure. The magnetometer studies indicated the low saturation
magnetization (23.96 emu/g) of CeO2 NPs for weak paramagnetic and high saturation
magnetization (32.13 emu/g) of CeO2 NPs for super paramagnetic. After that, the
oxidation effect of benzyl alcohol was investigated which reveals good conversion
and selectivity. Besides, the CeO2 NPs modified glassy carbon electrode (GCE)
used for the detection of nitrite with linear concentration range (0.02-1200
MUM), low limit of detection (0.21 MUM) and higher sensitivity (1.7238 MUAMUM-1
cm-2). However, the CeO2 NPs modified electrode has the fast response, high
sensitivity and good selectivity. In addition, the fabricated electrode is
applied for the determination of nitrite in various water samples. Eventually,
the CeO2 NPs can be regarded as an effective way to enhance the catalytic
activity towards the benzyl alcohol and nitrite.
PMID- 28406230
TI - Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer:
integrated bioinformatics analysis, experimental validation and diagnostic
evaluation.
AB - The aim of this study is to explore the differentially expressed lncRNAs, which
may have potential biological function and diagnostic value in colorectal cancer
(CRC). Through integrated data mining, we finally identified nine differentially
expressed lncRNAs and their potential mRNA targets. After a series of
bioinformatics analyses, we screened significant pathways and GO terms that are
related to the up-regulated and down-regulated transcripts respectively.
Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by
qRT-PCR and the results were basically consistent with the microarray data. We
also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC
tissue, 30 non-cancer patients and 30 health controls. Finally, we found that
BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC),
sensitivity and specificity were 0.858 (95% CI: 0.765-0.951), 83.3% and 76.7%
respectively between CRC patients and health controls. Moreover, BLACAT1 also had
distinct value to discriminate CRC from other non-cancer diseases. The results
indicated that the differentially expressed lncRNAs and their potential target
transcripts could be considered as potential therapeutic targets for CRC
patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker
for the diagnosis of CRC.
PMID- 28406232
TI - Peptidoglycan O-acetylation increases in response to vancomycin treatment in
vancomycin-resistant Enterococcus faecalis.
AB - Vancomycin resistance is conferred upon vancomycin-resistant enterococci (VRE)
through the replacement of peptidoglycan (PG) stem terminal d-Ala-d-Ala with d
Ala-d-Lac. The d-Ala-d-Lac incorporation can affect both the fitness and
virulence of VRE. Here we comprehensively investigate the changes to PG
composition in vancomycin-resistant Enterococcus faecalis following the growth in
presence of vancomycin using liquid chromatography-mass spectrometry. Using high
resolution mass spectrometry, 104 unique muropeptides fragments were identified
and the relative abundance of each fragment was accurately quantified by
integrating the ion current of a selected ion using extracted-ion chromatogram.
The analysis indicates reduced PG cross-linking, increased carboxypeptidase
activities, increased N-deacetylation, and increased O-acetylation in VRE when
grown in the presence of vancomycin. We found that O-acetylation preferentially
occurred on muropeptides fragments with reduced cross-linking with a pentapeptide
stem that terminated in d-Ala-d-Lac. These findings show that O-acetylation
preferentially occurred in regions of the cell wall with reduced PG cross-linking
on PG units that have stems terminating in d-Ala-d-Lac, serving as markers to
prevent both the PG-stem modification by carboxypeptidases and the cell wall
degradation by autolysins. Accurate quantitative PG composition analysis provided
compositional insights into altered cell wall biosynthesis and modification
processes in VRE that contribute to lysozyme resistance and enhanced virulence
for VRE grown in the presence of vancomycin.
PMID- 28406233
TI - Changes in prevalence, awareness, treatment and control of hypertension in
disadvantaged French Caribbean populations, 2003 to 2014.
AB - In 2003, the PHDG (Prevalence of Hypertension among Disadvantaged Guadeloupeans)
study highlighted poor management of hypertension in an unemployed French
Caribbean population. New processes of health-care coordination and a pay-for
performance system have since been developed. We aimed to assess changes in
hypertension characteristics in disadvantaged French Caribbean populations in the
last 10 years. Using PHDG 2003 data, in 2014 we undertook a cross-sectional study
with identical methods. The source population comprised all Guadeloupeans having
undergone periodic heath checks offered by the Social Security insurance at these
dates. Only universal health coverage beneficiaries (i.e. in situations of
poverty) aged 18-64 were included (2014 in 2014, 1868 in 2003). Hypertension was
defined by antihypertensive treatment or a mean of two blood pressure measures
?140/90 mm Hg. The 2003 and 2014 data were age adjusted; comparative morbidity
factors (CMF) and 95% confidence intervals were calculated to assess changes over
time. Hypertension prevalence decreased from 38.3 to 34.5% (CMF 95% CI: 0.83
0.97). The increase in hypertension awareness was greater for women (from 48.3 to
55.3%, CMF 95% CI: 1.00-1.31) than for men (from 28 to 31.1%, NS). Among
hypertensive individuals aware of their condition, proportions of those treated
increased for women (from 83.1 to 88.3%, NS) but decreased for men (from 80.2 to
75.8%, NS). Controlled hypertension among treated patients increased in women
(from 35.2 to 49.2%, CMF 95% CI: 1.07-1.82) and men (from 12.9 to 30.1%, CMF 95%
CI: 1.30-4.21). In conclusion, in these poor French Caribbean populations with
theoretically adequate access to care, hypertension control remained far below
national goals. Neither awareness nor treatment had improved in men.
PMID- 28406234
TI - Recommended standards for assessing blood pressure in human research where blood
pressure or hypertension is a major focus.
PMID- 28406235
TI - Physicochemical characterizations of functional hybrid liposomal nanocarriers
formed using photo-sensitive lipids.
AB - With recent advances in the field of diagnostics and theranostics, liposomal
technology has secured a fortified position as a potential nanocarrier.
Specifically, radiation/photo-sensitive liposomes containing photo-polymerizable
cross-linking lipids are intriguing as they can impart the vesicles with highly
interesting properties such as response to stimulus and improved shell stability.
In this work, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine
(DTPE) is used as a photo-polymerizable lipid to form functional hybrid-liposomes
as it can form intermolecular cross-linking through the diacetylenic groups.
Hybrid-liposomes were formulated using mixtures of DTPE and saturated lipids of
different chain lengths (dipalmitoylphosphatidylcholine (DPPC) and
dimirystoilphosphatidylcholine (DMPC)) at different molar ratios. The physico
chemical characteristics of the liposomes has been studied before and after UV
irradiation using a combination of techniques: DSC, QCM-D and solid-state NMR.
The results signify the importance of a subtle modification in alkyl chain length
on the phase behavior of the hybrid-liposomes and on the degree of crosslinking
in the shell.
PMID- 28406236
TI - Induced perpendicular magnetization in a Cu layer inserted between Co and Pt
layers revealed by x-ray magnetic circular dichroism.
AB - We used x-ray absorption spectroscopy and x-ray magnetic circular dichroism to
investigate the effects of inserting Cu into Co/Pt interfaces, and found that a
0.4-nm-thick inserted Cu layer showed perpendicularly magnetized properties
induced by the proximity effect through the Co and Pt layers. The dependence of
the magnetic properties on the thickness of the Cu layers showed that the
proximity effects between Co and Pt with perpendicular magnetic anisotropy can be
prevented by the insertion of a Cu layer with a nominal threshold thickness of
0.7 nm. Element-specific magnetization curves were also obtained, demonstrating
that the out-of-plane magnetization is induced in the Cu layers of the Co/Cu/Pt
structures.
PMID- 28406237
TI - Preference for facial averageness: Evidence for a common mechanism in human and
macaque infants.
AB - Human adults and infants show a preference for average faces, which could stem
from a general processing mechanism and may be shared among primates. However,
little is known about preference for facial averageness in monkeys. We used a
comparative developmental approach and eye-tracking methodology to assess visual
attention in human and macaque infants to faces naturally varying in their
distance from a prototypical face. In Experiment 1, we examined the preference
for faces relatively close to or far from the prototype in 12-month-old human
infants with human adult female faces. Infants preferred faces closer to the
average than faces farther from it. In Experiment 2, we measured the looking time
of 3-month-old rhesus macaques (Macaca mulatta) viewing macaque faces varying in
their distance from the prototype. Like human infants, macaque infants looked
longer to faces closer to the average. In Experiments 3 and 4, both species were
presented with unfamiliar categories of faces (i.e., macaque infants tested with
adult macaque faces; human infants and adults tested with infant macaque faces)
and showed no prototype preferences, suggesting that the prototypicality effect
is experience-dependent. Overall, the findings suggest a common processing
mechanism across species, leading to averageness preferences in primates.
PMID- 28406238
TI - New method for quantification of gasotransmitter hydrogen sulfide in biological
matrices by LC-MS/MS.
AB - Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in
physiological and pathophysiological processes. However, striking differences
with orders of magnitude were observed for the detected hydrogen sulfide
concentrations in biological matrices among different measurements in literature,
which lead to the uncertainty for examination the biological relevance of
hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass
spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in
various biological matrices by determination of a derivative of hydrogen sulfide
and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized
and validated for using as an internal standard. This method has been
successfully used to measure hydrogen sulfide levels in a broad range of
biological matrices, such as blood, plasma, tissues, cells, and enzymes, across
different species. Moreover, a novel mode that hydrogen sulfide could loosely and
non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed
by using the developed method.
PMID- 28406239
TI - CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and
vitro studies.
AB - Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of
anti-diabetic agent. The present study was designed to characterize the
pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our
laboratory, in vitro and in vivo. The IC50 of CMD-05 on DPP-IV inhibitory
activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In
diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05
inhibited DPP-IV activity, significantly improved glucose tolerance, increased
GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased
HbA1c and TG levels and improved the islet function without significantly effect
on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased
GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak
concentration at 30 min with half-life of 288 minutes and the inhibitory rate of
DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn't
cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin
in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These
results indicated that CMD-05 has similar activity with vildagliptin in vivo and
has a much longer half-life and lower cytotoxicity than vildagliptin.
PMID- 28406240
TI - Fast and simple high-capacity quantum cryptography with error detection.
AB - Quantum cryptography is commonly used to generate fresh secure keys with quantum
signal transmission for instant use between two parties. However, research shows
that the relatively low key generation rate hinders its practical use where a
symmetric cryptography component consumes the shared key. That is, the security
of the symmetric cryptography demands frequent rate of key updates, which leads
to a higher consumption of the internal one-time-pad communication bandwidth,
since it requires the length of the key to be as long as that of the secret. In
order to alleviate these issues, we develop a matrix algorithm for fast and
simple high-capacity quantum cryptography. Our scheme can achieve secure private
communication with fresh keys generated from Fibonacci- and Lucas- valued orbital
angular momentum (OAM) states for the seed to construct recursive Fibonacci and
Lucas matrices. Moreover, the proposed matrix algorithm for quantum cryptography
can ultimately be simplified to matrix multiplication, which is implemented and
optimized in modern computers. Most importantly, considerably information
capacity can be improved effectively and efficiently by the recursive property of
Fibonacci and Lucas matrices, thereby avoiding the restriction of physical
conditions, such as the communication bandwidth.
PMID- 28406241
TI - Fewer rainy days and more extreme rainfall by the end of the century in Southern
Africa.
AB - Future changes in the structure of daily rainfall, especially the number of rainy
days and the intensity of extreme events, are likely to induce major impacts on
rain-fed agriculture in the tropics. In Africa this issue is of primary
importance, but the agreement between climate models to simulate such descriptors
of rainfall is generally poor. Here, we show that the climate models used for the
fifth assessment report of IPCC simulate a marked decrease in the number of rainy
days, together with a strong increase in the rainfall amounts during the 1%
wettest days, by the end of the 21st century over Southern Africa. These combined
changes lead to an apparent stability of seasonal totals, but are likely to alter
the quality of the rainy season. These evolutions are due to the superposition of
slowly-changing moisture fluxes, mainly supported by increased hygrometric
capacity associated with global warming, and unchanged short-term atmospheric
configurations in which extreme events are embedded. This could cause enhanced
floods or droughts, stronger soil erosion and nutriment loss, questioning the
sustainability of food security for the 300 million people currently living in
Africa south of the Equator.
PMID- 28406242
TI - Decoupling of soil carbon and nitrogen turnover partly explains increased net
ecosystem production in response to nitrogen fertilization.
AB - During the last decade there has been an ongoing controversy regarding the extent
to which nitrogen fertilization can increase carbon sequestration and net
ecosystem production in forest ecosystems. The debate is complicated by the fact
that increased nitrogen availability caused by nitrogen deposition has coincided
with increasing atmospheric carbon dioxide concentrations. The latter could
further stimulate primary production but also result in increased allocation of
carbon to root exudates, which could potentially 'prime' the decomposition of
soil organic matter. Here we show that increased input of labile carbon to forest
soil caused a decoupling of soil carbon and nitrogen cycling, which was
manifested as a reduction in respiration of soil organic matter that coincided
with a substantial increase in gross nitrogen mineralization. An estimate of the
magnitude of the effect demonstrates that the decoupling could potentially result
in an increase in net ecosystem production by up to 51 kg C ha-1 day-1 in
nitrogen fertilized stands during peak summer. Even if the effect is several
times lower on an annual basis, the results still suggest that nitrogen
fertilization can have a much stronger influence on net ecosystem production than
can be expected from a direct stimulation of primary production alone.
PMID- 28406243
TI - Stepwise cycloaddition reaction of N-phenacylbenzothiazolium bromides and
nitroalkenes for tetrahydro-, dihydro- and benzo[d]pyrrolo[2,1-b]thiazoles.
AB - The triethylamine promoted stepwise 1,3-dipolar cycloaddition reaction of N
phenacylbenzothiazolium bromides with nitroalkenes in ethanol resulted in a
mixture of two isomeric tetrahydrobenzo[d]pyrrolo[2,1-b]thiazoles with
cis/trans/cis- and all-trans-configurations. More importantly, the corresponding
dihydrobenzo[d]pyrrolo[2,1-b]thiazoles can be selectively prepared in refluxing
ethanol and the benzo[d]pyrrolo[2,1-b]thiazoles can be obtained in satisfactory
yields by sequential dehydrogenation with DDQ as oxidizer. On the other hand, the
similar cycloaddition reaction of N-phenacylbenzothiazolium bromides with 1-methy
1-nitroalkenes in refluxing ethanol afforded benzo[d]pyrrolo[2,1-b]thiazoles with
splitting out of nitro group. The stereochemistry of the spiro compounds was
clearly elucidated on the basis of NMR spectra and sixteen single crystal
structures.
PMID- 28406244
TI - Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the
formation of foam cells.
AB - Atherosclerosis is a chronic inflammatory cardiovascular disease that is
responsible of high mortality worldwide. Evidence indicates that maladaptive
autoimmune responses in the arterial wall play critical roles in the process of
atherosclerosis. Cortistatin is a neuropeptide expressed in the vascular system
and atherosclerotic plaques that regulates vascular calcification and neointimal
formation, and inhibits inflammation in different experimental models of
autoimmune diseases. Its role in inflammatory cardiovascular disorders is largely
unexplored. The aim of this study is to investigate the potential therapeutic
effects of cortistatin in two well-established preclinical models of
atherosclerosis, and the molecular and cellular mechanisms involved. Systemic
treatment with cortistatin reduced the number and size of atherosclerotic plaques
in carotid artery, heart, aortic arch and aorta in acute and chronic
atherosclerosis induced in apolipoprotein E-deficient mice fed a high-lipid diet.
This effect was exerted at multiple levels. Cortistatin reduced Th1/Th17-driven
inflammatory responses and increased regulatory T cells in atherosclerotic
arteries and lymphoid organs. Moreover, cortistatin reduced the capacity of
endothelial cells to bind and recruit immune cells to the plaque and impaired the
formation of foam cells by enhancing cholesterol efflux from macrophages.
Cortistatin emerges as a new candidate for the treatment of the clinical
manifestations of atherosclerosis.
PMID- 28406245
TI - Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular
inflammation.
AB - High dietary salt (NaCl) is a known risk factor for cardiovascular pathologies
and inflammation. High plasma Na+ concentrations (high Na+) have been shown to
stiffen the endothelial cortex and decrease nitric oxide (NO) release, a hallmark
of endothelial dysfunction. Here we report that chronic high Na+ damages the
endothelial glycocalyx (eGC), induces release of inflammatory cytokines from the
endothelium and promotes monocyte adhesion. Single cell force spectroscopy
reveals that high Na+ enhances vascular adhesion protein-1 (VCAM-1)-dependent
adhesion forces between monocytes and endothelial surface, giving rise to
increased numbers of adherent monocytes on the endothelial surface.
Mineralocorticoid receptor antagonism with spironolactone prevents high Na+
induced eGC deterioration, decreases monocyte-endothelium interactions, and
restores endothelial function, indicated by increased release of NO. Whereas high
Na+ decreases NO release, it induces endothelial release of the pro-inflammatory
cytokines IL-1beta and TNFalpha. However, in contrast to chronic salt load
(hours), in vivo and in vitro, an acute salt challenge (minutes) does not impair
eGC function. This study identifies the eGC as important mediator of inflammatory
processes and might further explain how dietary salt contributes to
endothelialitis and cardiovascular pathologies by linking endothelial
nanomechanics with vascular inflammation.
PMID- 28406246
TI - Unravelling mycorrhiza-induced wheat susceptibility to the English grain aphid
Sitobion avenae.
AB - Arbuscular mycorrhizal (AM) fungi are root symbionts that can increase or
decrease aphid growth rates and reproduction, but the reason by which this
happens is unknown. To investigate the underlying mechanisms of this interaction,
we examined the effect of AM fungi on the English Grain aphid (Sitobion avenae)
development, reproduction, attraction, settlement and feeding behaviour on two
naturally susceptible varieties Triticum aestivum (L.) variety Solstice and T.
monococcum MDR037, and two naturally resistant lines, T. monococcum MDR045 and
MDR049. Mycorrhizal colonisation increased the attractiveness of T. aestivum var.
Solstice to aphids, but there was no effect on aphid development on this variety.
Using the Electrical Penetration Graph (EPG) technique, we found that mycorrhizal
colonisation increased aphid phloem feeding on T. monococcum MDR037 and MDR045,
colonisation also increased growth rate and reproductive success of S. avenae on
these varieties. Mycorrhizas increased vascular bundle size, demonstrating that
these fungi can influence plant anatomy. We discuss if and how this could be
related to an enhanced success rate in phloem feeding in two varieties. Overall,
we present and discuss how mycorrhizal fungi can affect the feeding behaviour of
S. avenae in wheat, inducing susceptibility in a resistant variety.
PMID- 28406247
TI - HbA1c level cannot predict the treatment outcome of smear-positive non-multi-drug
resistant HIV-negative pulmonary tuberculosis inpatients.
AB - We conducted a single-center retrospective cohort study to evaluate whether the
HbA1c level on admission could predict the in-hospital treatment outcome of smear
positive non-multi-drug-resistant HIV-negative culture-proven pulmonary
tuberculosis inpatients. Our standard regimens under the direct observation were
HRZE or HRE for the first two months followed by combination therapy with
isoniazid and rifampicin. Our cohort consisted of consecutive 239 patients
consisted of 147 men and 92 women with a median age of 73 years. The HbA1c level
of patients whose HbA1c was above 7.0% on admission showed clear declining trends
after admission. HbA1c on admission had no Spearman's rank correlation with time
to discharge alive (r = 0.17) and time to becoming non-infective (r = 0.17). By
Kaplan-Meier curves and a log-rank trend test, HbA1c quartile subgroups showed no
association with times to discharge alive (p = 0.431), becoming non-infective (p
= 0.113), and in-hospital death (p = 0.427). Based on multi-variate Cox analysis,
HbA1c on admission had no significant impact on time to discharge alive (hazard
ratio = 1.03, 95% CI 0.89-1.20, p = 0.659), becoming non-infective (hazard ratio
= 0.93, 95% CI 0.80-1.06, p = 0.277), and in-hospital death (hazard ratio = 0.68,
0.43-1.07, p = 0.097). In conclusion, the HbA1c level on admission did not seem
to affect in-hospital tuberculosis treatment outcomes in Japanese cohort.
PMID- 28406256
TI - Dynamic covalent chemistry in aqueous solution by photoinduced radical disulfide
metathesis.
AB - Photoinduced radical disulfide metathesis (PRDM) is a dynamic covalent reaction
that requires UV light to induce the homolytic cleavage of the disulfide bond,
thus offering the opportunity to construct dynamic covalent systems that are
dormant and can be photo-activated on demand. In this work, we showcase how PRDM
can be utilized in aqueous solution and demonstrate its potential by generating a
UV responsive hydrogel from an asymmetrical disulfide precursor.
PMID- 28406248
TI - Sensory defects and developmental delay among children with congenital rubella
syndrome.
AB - This study investigated the features of developmental difficulties combined with
sensory defects in children with congenital rubella syndrome (CRS). Following a
large rubella outbreak in Khanh Hoa Province, Vietnam, in 2011, we enrolled 41
children with CRS from September 2011 through May 2013. Fourteen participants
died and six became untraceable by October 2013; the remaining 21 children were
followed up from 2013 to 2015. Thirteen and seven participants had hearing and
functional ophthalmological impairment, respectively. Developmental difficulties
were suspected in 19 (95%) children who failed in at least one area of the Ages
and Stages Questionnaire (ASQ) and/or Denver II in 2013 and/or 2015.
Developmental difficulties were frequently identified in the ASQ communication
domain (n = 14 in 2013) and Denver II language area (n = 13 in 2013). Seven (41%)
participants were suspected of having autism spectrum disorder (ASD) in 2013 by
the Modified Checklist for Autism in Toddlers. In 2015, proportions of children
failing the problem-solving (62%) and personal-social (62%) domains had increased
and two of 13 were diagnosed with ASD by the Childhood Autism Rating Scale,
Second Edition. Developmental difficulties were suspected in most children with
CRS, including autism largely combined with sensory dysfunction.
PMID- 28406257
TI - Nitrogen-doped carbon encapsulating gamma-MoC/Ni heterostructures for efficient
oxygen evolution electrocatalysts.
AB - Developing efficient and earth-abundant oxygen evolution reaction (OER)
electrocatalysts is of great importance in renewable energy research. Herein, we
report nitrogen-doped carbon encapsulating gamma-MoC/Ni heterostructures (gamma
MoC/Ni@NC) for the first time as efficient OER electrocatalysts. The composites
can be controlled by the addition of a Mo source to form a nanoparticle-assembled
hierarchically porous nanostructure, which can enlarge the specific surface area,
thus exposing more active sites. Moreover, we demonstrate that the formation of
gamma-MoC@Ni heterostructures and the resulting synergistic effect between gamma
MoC and Ni can facilitate the reaction kinetics, leading to significantly
improved OER activity with an onset overpotential of merely 240 mV, and a low
overpotential of 310 mV to afford a current density of 10 mA cm-2. This work
provides a new insight into the development of highly active and inexpensive OER
electrocatalysts.
PMID- 28406258
TI - A new Dirac cone material: a graphene-like Be3C2 monolayer.
AB - Two-dimensional (2D) materials with Dirac cones exhibit rich physics and many
intriguing properties, but the search for new 2D Dirac materials is still a
current hotspot. Using the global particle-swarm optimization method and density
functional theory, we predict a new stable graphene-like 2D Dirac material: a
Be3C2 monolayer with a hexagonal honeycomb structure. The Dirac point occurs
exactly at the Fermi level and arises from the merging of the hybridized pz bands
of Be and C atoms. Most interestingly, this monolayer exhibits a high Fermi
velocity in the same order of graphene. Moreover, the Dirac cone is very robust
and retains even included spin-orbit coupling or external strain. These
outstanding properties render the Be3C2 monolayer a promising 2D material for
special electronics applications.
PMID- 28406259
TI - Copper-catalysed enantioselective Michael addition of malonic esters to beta
trifluoromethyl-alpha,beta-unsaturated imines.
AB - Copper triflate-BOX complexes catalyse the enantioselective conjugate addition of
methyl malonate to beta-trifluoromethyl-alpha,beta-unsaturated imines to give the
corresponding enamines bearing a trifluoromethylated stereogenic centre with good
yields, and diastereo- and enantioselectivities. The usefulness of the method has
been shown with the synthesis of optically active beta-trifluoromethyl delta
amino esters and optically active trifluoromethyl piperidones.
PMID- 28406262
TI - Bulk iron pyrite as a catalyst for the selective hydrogenation of nitroarenes.
AB - Bulk iron pyrite (FeS2) functions as an inexpensive, Earth-abundant, off-the
shelf catalyst capable of selectively hydrogenating a broad scope of substituted
nitroarenes to their corresponding aniline derivatives using molecular hydrogen.
PMID- 28406263
TI - Pharmacotherapy for hyperuricemia in hypertensive patients.
AB - BACKGROUND: High blood pressure represents a major public health problem.
Worldwide, approximately one-fourth of the adult population has hypertension.
Epidemiological and experimental studies suggest a link between hyperuricemia and
hypertension. Hyperuricemia affects 25% to 40 % of individuals with untreated
hypertension; a much lower prevalence has been reported in normotensives or in
the general population. However, whether lowering serum uric acid (UA) might
lower blood pressure (BP) is an unanswered question. OBJECTIVES: To determine
whether UA-lowering agents reduce BP in patients with primary hypertension or
prehypertension compared with placebo. SEARCH METHODS: The Cochrane Hypertension
Information Specialist searched the following databases for randomized controlled
trials up to February 2016: the Cochrane Hypertension Specialised Register, the
Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 2), MEDLINE
(from 1946), Embase (from 1974), the World Health Organization International
Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched
LILACS up to March 2016 and contacted authors of relevant papers regarding
further published and unpublished work. SELECTION CRITERIA: To be included in
this review, the studies had to meet the following criteria: 1) randomized or
quasi-randomized, with a group assigned to receive a UA-lowering agent and
another group assigned to receive placebo; 2) double-blind, single-blind or open
label; 3) parallel or cross-over trial; 4) cross-over trials had to have a
washout period of at least two weeks; 5) minimum treatment duration of four
weeks; 6) participants had to have a diagnosis of essential hypertension or
prehypertension, and hyperuricemia (serum UA greater than 6 mg/dL in women, 7
mg/dL in men and 5.5 mg/dL in children/adolescents); 7) outcome measures assessed
included change in clinic systolic, diastolic or 24-hour ambulatory BP. DATA
COLLECTION AND ANALYSIS: The two review authors independently collected the data
using a data extraction form, and resolved any disagreements via discussion. We
assessed risk of bias using the Cochrane Collaboration' Risk of bias' tool. MAIN
RESULTS: In this review update, we examined the abstracts of 349 identified
papers and selected 21 for evaluation. We also identified three ongoing studies,
the results of which are not yet available. Three other randomized controlled
trials (RCTs) (two new), enrolling individuals with hypertension or
prehypertension, and hyperuricemia, met the inclusion criteria for the review and
were included in the meta-analysis. Low quality of evidence from three RCTs
indicate no reduction in systolic (MD -6.2 mmHg, 95% CI -12.8 to 0.5) or
diastolic (-3.9 mmHg, 95% CI -9.2 to 1.4) 24-hour ambulatory BP with UA-lowering
drugs compared with placebo. Low quality of evidence from two RCTs reveal a
reduction of systolic clinic BP (-8.43 mmHg, 95% CI -15.24 to -1.62) but not
diastolic clinic BP (-6.45 mmHg, 95% CI -13.60 to 0.70). High quality of evidence
from three RCTs indicates that serum UA levels were reduced by 3.1 mg/dL (95% CI
2.4 to 3.8) in the participants that received UA-lowering drugs. Very low quality
of evidence from three RCTs suggests that withdrawals due to adverse effects were
not increased with UA-lowering therapy (RR 1.86, 95% CI 0.43 to 8.10). AUTHORS'
CONCLUSIONS: In this updated systematic review, the RCT data available at present
are insufficient to know whether UA-lowering therapy also lowers BP. More studies
are needed.
PMID- 28406264
TI - Persistent Low Rates of Treatment of Metabolic Risk Factors in People With
Psychotic Disorders: A PHAMOUS Study.
AB - OBJECTIVE: People with psychotic disorders have an increased metabolic risk and a
shortened life expectancy compared to the general population. Two large studies
showed that metabolic disorders were untreated in a majority of the patients.
Since then, guidelines have urged monitoring of metabolic health. This study
examined the course of metabolic disorders over time in people with psychotic
disorders and investigated current treatment rates. METHODS: A total of 1,259
patients with psychotic disorders, as defined by the DSM-IV, from 4 Dutch mental
health institutions participated in 3 yearly assessments of the Pharmacotherapy
Monitoring and Outcome Survey (PHAMOUS) between 2006 and 2014. Patients'
metabolic parameters were measured, and the use of pharmacologic treatment for
hypertension (systolic blood pressure >= 140 mm Hg and/or diastolic blood
pressure >= 90 mm Hg), dyslipidemia (5% <= Systematic COronary Risk Evaluation
[SCORE] risk < 10% and low-density lipoprotein [LDL] cholesterol level >= 2.5
mmol/L or SCORE risk >= 10% and LDL cholesterol level >= 1.8 mmol/L and/or
triglycerides >= 2.3 mmol/L), and hyperglycemia (hemoglobin A1c concentration >
7% and/or fasting glucose concentration >= 7.2 mmol/L) was recorded. RESULTS:
Prevalence of the metabolic syndrome, as defined by the National Cholesterol
Education Program criteria, was > 50% at each assessment. On the basis of the
European Society of Cardiology guidelines, pharmacotherapy for metabolic
disorders was recommended for 52%-59% of the patients at each assessment.
Treatment rates with antihypertensive (from 31% to 38%, P < .001) pharmacotherapy
increased throughout the assessments. However, half of the patients were not
treated for their metabolic risk factors while being monitored for 3 years or
longer. Older patients were more likely to receive treatment, and patients who
received treatment had lower blood pressure and lower cholesterol and
triglyceride concentrations than patients not receiving the recommended
treatment. CONCLUSIONS: Metabolic risk factors are still seriously undertreated
in people with psychotic disorders. Better adherence to and better implementation
of guidelines about monitoring and treating metabolic disorders in psychiatry are
crucial.
PMID- 28406265
TI - Symptoms of Apathy Independently Predict Incident Frailty and Disability in
Community-Dwelling Older Adults.
AB - OBJECTIVE: Although depressive symptoms are widely recognized as a predictor of
functional decline among older adults, little is known about the predictive
utility of apathy in this population. We prospectively examined apathy symptoms
as predictors of incident slow gait, frailty, and disability among non-demented,
community-dwelling older adults. METHODS: We examined 2 independent prospective
cohort studies-the LonGenity study (N = 625, 53% women, mean age = 75.2 years)
and the Central Control of Mobility in Aging (CCMA) study (N = 312, 57% women,
mean age = 76.4 years). Individuals were recruited from 2008 to 2014. Apathy was
assessed using 3 items from the Geriatric Depression Scale. Slow gait was defined
as 1 standard deviation or more below age- and sex-adjusted mean values, frailty
was defined using the Cardiovascular Health Study criteria, and disability was
assessed with a well-validated disability scale. RESULTS: The prevalence of
apathy was 20% in the LonGenity cohort and 26% in the CCMA cohort. The presence
of apathy at baseline, independent of depressive symptoms (besides apathy),
increased the risk of developing incident slow gait (hazard ratio [HR] = 2.10;
95% CI, 1.36-3.24; P = .001), frailty (HR = 2.86; 95% CI, 1.96-4.16; P < .001),
and disability (HR = 3.43; 95% CI, 1.73-6.79; P < .001) in the pooled sample.
These associations remained significant when accounting for demographics, medical
illnesses, and cognitive function. CONCLUSIONS: Apathy is associated with
increased risk of developing slow gait, frailty, and disability, independent of
other established risk factors, in non-demented older adults. Apathy should be
screened for as a potentially preventable cause of functional decline in clinical
psychiatric settings.
PMID- 28406266
TI - The 3-Year Course of Multiple Substance Use Disorders in the United States: A
National Longitudinal Study.
AB - OBJECTIVE: To examine the 3-year course of multiple co-occurring substance use
disorders (SUDs) based on longitudinal survey data from a large, nationally
representative sample. METHODS: National estimates of the prevalence of DSM-IV
SUDs were derived by analyzing data from structured, face-to-face diagnostic
interviews as part of the National Epidemiologic Survey on Alcohol and Related
Conditions (NESARC), which collected data from a large, nationally representative
sample of noninstitutionalized US adults at 2 waves (2001-2002 and 2004-2005; N =
34,653). RESULTS: US adults with multiple past-year SUDs at Wave 1 were
substantially more likely than those with an individual past-year SUD or no SUD
at Wave 1 to report at least 1 past-year SUD at Wave 2 (66.3% vs 46.0% vs 6.9%,
respectively). There were several sociodemographic characteristics and
psychiatric disorders (ie, male, younger age, never married, sexual minority
identity, nicotine dependence, mood disorder, and personality disorder)
associated with increased odds of developing multiple SUDs and having 3-year
persistence of multiple SUDs. The majority of adults with multiple past-year SUDs
had a lifetime personality disorder and did not utilize substance abuse treatment
or other help-seeking. CONCLUSIONS: Multiple SUDs are associated with a more
persistent 3-year course of disease over time relative to individual SUDs.
Despite a more severe 3-year course and higher rates of comorbidity with other
psychiatric disorders, the majority of US adults with multiple SUDs do not
utilize substance abuse treatment or other help-seeking. Clinical assessments and
the substance abuse literature tend to focus on drug-specific individual SUDs
rather than considering the more complex multiple SUDs, which can be more
challenging to treat.
PMID- 28406267
TI - Long-Term Antipsychotic Use and Major Cardiovascular Events: A Retrospective
Cohort Study.
AB - OBJECTIVE: Chronic treatment with antipsychotics may result in both metabolic
side effects and cardiovascular disease. Our aim was to evaluate the effect of
antipsychotic medications categorized by their metabolic side effect profiles as
low, intermediate, or high risk on major cardiovascular events. METHODS: A
retrospective cohort study was conducted in adult outpatients aged 30 years or
older initiating antipsychotic treatment from 2002 to 2007. Antipsychotic
medications were divided into 3 groups (low-, intermediate-, and high-risk)
according to the severity of their side-effect profiles in developing metabolic
abnormalities associated with cardiovascular disease. The primary outcome measure
was the time to the composite of acute myocardial infarction, acute coronary
syndrome, ischemic stroke, peripheral artery disease, or a new revascularization
procedure. Inverse probability weighting of a marginal structural Cox model was
used to adjust for confounding. RESULTS: A total of 1,008 patients were included
(mean age = 72.4 years, median follow-up = 36.5 months), and 19.6% of patients
experienced the primary outcome. The adjusted hazard ratios of a major
cardiovascular event for patients in the high- or intermediate-risk medication
groups compared to the low-risk group were 2.82 (95% CI, 1.57-5.05) and 2.57 (95%
CI, 1.43-4.63), respectively. CONCLUSIONS: Older adult patients under
antipsychotic regimens with high or intermediate risk of metabolic side effects
may face a higher incidence of major cardiovascular events than those under a low
risk regimen during long-term follow-up.
PMID- 28406268
TI - Self-Reported Reasons for Not Receiving Mental Health Treatment in Adults With
Serious Suicidal Thoughts.
AB - OBJECTIVE: This study examined self-reported reasons for not receiving mental
health treatment among adults with past-year serious suicidal thoughts and their
sociodemographic characteristics associated with these reasons. METHODS: Using
the 2008-2013 National Surveys on Drug Use and Health, we examined 8,400
respondents aged 18 years or older who had past-year serious thoughts of suicide
and did not receive mental health treatment that year. Logistic regression
analyses were conducted to estimate the associations between sociodemographic
characteristics and self-reported reasons for not receiving mental health
treatment among these suicidal adults. RESULTS: Among adults with serious
suicidal thoughts who did not receive mental health treatment in the past year,
three-fourths did not feel the need for treatment. Of the one-fourth of those who
felt the need for treatment, the main reason for not receiving treatment was
financial (58.4%), followed by logistical reasons such as not knowing where to go
(36.1%). A greater proportion of suicidal adults than nonsuicidal adults
perceived more than 1 barrier to treatment (43.8% vs 34.3%). Among suicidal
adults who did not receive mental health treatment that year, the odds of not
feeling the need for mental health treatment were higher in men (adjusted odds
ratio [AOR] = 1.68; 95% CI, 1.42-1.99), adults aged 50 years or older (AOR =
3.02; 95% CI, 2.02-4.51), racial and ethnic minorities (AORs = 1.59-2.13),
publicly insured (AOR = 1.54; 95% CI, 1.14-2.07), and nonmetropolitan residents
(AOR = 1.50; 95% CI, 1.20-1.88). CONCLUSIONS: Most suicidal adults did not feel
the need for mental health treatment. Of those who felt the need, multiple
barriers were identified. A multifaceted approach to address these barriers is
needed to promote receipt of mental health treatment among this vulnerable
population.
PMID- 28406269
TI - Evaluating the feasibility and uptake of a community-led HIV testing and multi
disease health campaign in rural Uganda.
AB - INTRODUCTION: Multi-disease community health campaigns can be effective for
population-wide HIV testing in a research setting (SEARCH: NCT01864603). We
sought to evaluate feasibility and uptake of a community-led health campaign
(CLHC) planned and implemented by village leaders and local clinic workers in
Uganda. METHODS: Over five months in 2014, locally elected village leaders and
Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a
census followed by a CLHC, after training by two SEARCH trial consultants and by
leaders from a neighbouring parish that had previously participated in a SEARCH
health campaign. We defined feasibility as: (1) elected leaders' participation in
training and implementation of pre-campaign census and mobilization activities;
(2) implementation of all campaign activities by MoH-funded, local clinic staff;
and (3) community participation in the campaign, including point-of-care
screening for HIV, malaria, hypertension and diabetes, and same-day referral for
male circumcision and family planning (FP). Costing of all salaries and supplies
was conducted. RESULTS: Elected leaders from all eight villages in the parish
participated in CLHC training. They and local clinic staff met monthly to select
and plan CLHC services. Village leaders then leveraged existing volunteer health
teams to perform a door-to-door census, enumerating 5,202 parish residents over 2
weeks. 2,753 (53%) residents participated in the 6-day CLHC. Of 1,584 adult
participants, 1,474 (93%) tested for HIV: 105/1,474 (7.1%) tested HIV positive.
27% (751/2,753) of participants reported fever and underwent malaria rapid
diagnostic testing: 5.3% (40/751) tested positive. Among adults screened, 19%
(271/1,452) were hypertensive, and 3% (18/637) had a random blood sugar >11.1
mmol/L. Of 805 men and boys (>10 years), 91 (11%) accepted same-day clinic
referral and underwent medical circumcision. Of 900 women offered same-day long
term FP referrals, 25 accepted. The CLHC cost, including census, mobilization and
testing services, was $23,597 ($8.57/participant). CONCLUSION: Elected village
leaders successfully planned and conducted a 6-day multi-disease health campaign
with service provision by local clinic staff that reached over half of a rural
Ugandan community. These data suggest it is feasible for local leaders and
clinics to adopt a multi-disease health campaign approach to scale-up HIV testing
in rural Africa.
PMID- 28406270
TI - Community engagement in sexual health and uptake of HIV testing and syphilis
testing among MSM in China: a cross-sectional online survey.
AB - INTRODUCTION: HIV and syphilis testing rates remain low among men who have sex
with men (MSM) in low- and middle-income countries (LMICs). Community engagement
has been increasingly used to promote HIV testing among key populations in high
income countries, often in settings with stronger civil society. This study aimed
to assess socio-demographic, behavioural, and community engagement factors
associated with HIV and syphilis testing among MSM in China. METHODS: MSM >=16
years old who had condomless sex in the past three months were recruited
nationwide to complete a cross-sectional online survey in November 2015. Data
were collected on socio-demographics, sexual behaviours, HIV testing, syphilis
testing, and community engagement in sexual health. We defined community
engagement in sexual health using six items assessing awareness and advocacy of
sexual health programmes. The underlying factor structure of a 6-item community
engagement scale was determined through exploratory factor analysis. Univariate
and multivariable logistic regressions identified correlates of HIV and syphilis
testing. RESULTS: 1189 MSM were recruited. 54% (647/1189) of men had ever tested
for HIV and 30% (354/1189) had ever tested for syphilis. Factor analysis
suggested three levels of community engagement (minimal, moderate, and
substantial) and this model explained 79.5% of observed variance. A quarter (26%,
312/1189) reported none to minimal engagement, over one half (54%, 644/1189)
reported moderate engagement, and a fifth (20%, 233/1189) reported substantial
engagement. Multivariable logistic regression showed that MSM with greater
community engagement in sexual health were more likely to have ever tested for
HIV (substantial vs. no engagement: aOR 7.91, 95% CI 4.98-12.57) and for syphilis
(substantial vs. no engagement: aOR 5.35, 95% CI 3.16-9.04). CONCLUSION: HIV and
syphilis testing are suboptimal among MSM in China. Community engagement may be
useful for promoting testing in China and should be considered in intervention
development and delivery. Further research is needed to better understand the
role of LMIC community engagement in HIV interventions.
PMID- 28406271
TI - The relationship between higher social trust and lower late HIV diagnosis and
mortality differs by race/ethnicity: results from a state-level analysis.
AB - INTRODUCTION: Black men who have sex with men (MSM) continue to suffer a
disproportionate burden of new HIV diagnoses and mortality. To better understand
some of the reasons for these profound disparities, we examined whether the
association between social trust and late HIV diagnosis and mortality differed by
race/ethnicity, and investigated potential indirect effects of any observed
differences. METHODS: We performed generalized structural equation modelling to
assess main and interaction associations between trust among one's neighbours in
2009 (i.e. social trust) and race/ethnicity (Black, White, and Hispanic)
predicting late HIV diagnosis (a CD4 count <=200 cell/uL within three months of a
new HIV diagnosis) rates and all-cause mortality rates of persons ever diagnosed
late with HIV, across 47 American states for the years 2009-2013. We examined
potential indirect effects of state-level HIV testing between social trust and
late HIV diagnosis. Social trust data were from the Gallup Healthways Survey, HIV
data from the Centers for Disease Control and Prevention, and HIV testing from
the Behavioral Risk Factor Surveillance System. Covariates included state-level
structural, healthcare, and socio-demographic factors including income
inequality, healthcare access, and population density. We stratified analysis by
transmission group (male-to-male, heterosexual, and injection drug use (IDU)).
RESULTS: States with higher levels of social trust had lower late HIV diagnosis
rates: Adjusted Rate Ratio [aRR] were consistent across risk groups (0.57; 95%CI
0.53-0.62, male-to-male), (aRR 0.58; 95%CI 0.54-0.62, heterosexual) and (aRR
0.64; 95%CI 0.60-0.69, IDU). Those associations differed by race/ethnicity (all p
< 0.001). The associations were most protective for Blacks followed by Hispanics,
and least protective for Whites. HIV testing mediated between 18 and 32% of the
association between social trust and late HIV diagnosis across transmission group
but for Blacks relative to Whites only. Social trust was associated with lower
all-cause mortality rates and that association varied by race/ethnicity within
the male-to-male and IDU transmission groups only. CONCLUSION: Social trust may
promote timely HIV testing, which can facilitate earlier HIV diagnosis, thus it
can be a useful determinant to monitor the relationship with HIV care continuum
outcomes especially for racial/ethnic minority groups disproportionately infected
by HIV.
PMID- 28406272
TI - Dorsal longitudinal foreskin cut is associated with reduced risk of HIV, syphilis
and genital herpes in men: a cross-sectional study in Papua New Guinea.
AB - INTRODUCTION: Various forms of penile foreskin cutting are practised in Papua New
Guinea. In the context of an ecological association observed between HIV
infection and the dorsal longitudinal foreskin cut, we undertook an investigation
of this relationship at the individual level. METHODS: We conducted a cross
sectional study among men attending voluntary confidential HIV counselling and
testing clinics. Following informed consent, participants had a face-to-face
interview and an examination to categorize foreskin status. HIV testing was
conducted on site and relevant specimens collected for laboratory-based Herpes
simplex type-2 (HSV-2), syphilis, Chlamydia trachomatis (CT), Neisseria
gonorrhoeae (NG), and Trichomonas vaginalis (TV) testing. RESULTS: Overall, 1073
men were enrolled: 646 (60.2%) were uncut; 339 (31.6%) had a full dorsal
longitudinal cut; 72 (6.7%) a partial dorsal longitudinal cut; and 14 (1.3%) were
circumcised. Overall, the prevalence of HIV was 12.3%; HSV-2, 33.6%; active
syphilis, 12.1%; CT, 13.4%; NG, 14.1%; and TV 7.6%. Compared with uncut men, men
with a full dorsal longitudinal cut were significantly less likely to have HIV
(adjusted odds ratio [adjOR] 0.25, 95%CI: 0.12, 0.51); HSV-2 (adjOR 0.60, 95%CI:
0.41, 0.87); or active syphilis (adjOR 0.55, 95%CI: 0.31, 0.96). This apparent
protective effect was restricted to men cut prior to sexual debut. There was no
difference between cut and uncut men for CT, NG or TV. CONCLUSION: In this large
cross-sectional study, men with a dorsal longitudinal foreskin cut were
significantly less likely to have HIV, HSV-2 and syphilis compared with uncut
men, despite still having a complete (albeit morphologically altered) foreskin.
The protective effect of the dorsal cut suggests that the mechanism by which male
circumcision works is not simply due to the removal of the inner foreskin and its
more easily accessible HIV target cells. Exposure of the penile glans and inner
foreskin appear to be key mechanisms by which male circumcision confers
protection.Further research in this unique setting will help improve our
understanding of the fundamental immunohistologic mechanisms by which male
circumcision provides protection, and may lead to new biomedical prevention
strategies at the mucosal level.
PMID- 28406273
TI - "We are part of a family". Benefits and limitations of community ART groups
(CAGs) in Thyolo, Malawi: a qualitative study.
AB - INTRODUCTION: In 2012 Community ART Groups (CAGs), a community-based model of
antiretroviral therapy (ART) delivery were piloted in Thyolo District, Malawi as
a way to overcome patient barriers to accessing treatment, and to decrease
healthcare workers' workload. CAGs are self-formed groups of patients on ART
taking turns to collect ART refills for all group members from the health
facility. We conducted a qualitative study to assess the benefits and challenges
of CAGs from patients' and healthcare workers' (HCWs) perspectives. METHODS: Data
were collected by means of 15 focus group discussions, 15 individual in-depth
interviews, and participant observation in 2 health centres. The 94 study
participants included CAG members, ART patients eligible for CAGs who remained in
conventional care, former CAG members who returned to conventional care and HCWs
responsible for providing HIV care. Patient participants were purposively
selected from ART registers, taking into account age and gender. Narratives were
audio-recorded, transcribed, and translated from Chichewa to English. Data were
analyzed through a thematic analysis. RESULTS: Patients and HCWs spoke favourably
about the practical benefits of CAGs. Patient benefits included a reduced
frequency of clinic visits, resulting in reduced transportation costs and time
savings. HCW benefits included a reduced workload. Additionally peer support was
perceived as an added value of the groups allowing not only sharing of the
logistical constraints of drugs refills, but also enhanced emotional support.
Identified barriers to joining a CAG included a lack of information on CAGs,
unwillingness to disclose one's HIV status, change of residence and conflicts
among CAG members. Participants reported that HIV-related stigma persists and
CAGs were seen as an effective strategy to reduce exposure to discriminatory
labelling by community members. CONCLUSION: In this setting, patients and HCWs
perceived CAGs to be an acceptable model of ART delivery. Despite addressing
important practical barriers to accessing ART, and providing peer support, CAGs
were not well known by patients and had a limited impact on reducing HIV-related
stigma. The CAG model of ART delivery should be considered in similar settings.
Further measures need to be devised and implemented to address HIV-related
stigma.
PMID- 28406275
TI - High self-reported non-adherence to antiretroviral therapy amongst adolescents
living with HIV in Malawi: barriers and associated factors.
AB - INTRODUCTION: Globally adolescents and young adults account for more than 40% of
new HIV infections, and HIV-related deaths amongst adolescents increased by 50%
from 2005 to 2012. Adherence to antiretroviral therapy (ART) is critical to
control viral replication and preserve health; however, there is a paucity of
research on adherence amongst the growing population of adolescents living with
HIV/AIDS (ALHIV) in Southern Africa. We examined levels of self-reported ART
adherence, barriers to adherence, and factors associated with non-adherence
amongst ALHIV in Malawi. METHODS: Cross-sectional study of 519 ALHIV (12-18
years) attending two large HIV clinics in central and south-eastern Malawi.
Participants self-reported missed doses (past week/month), barriers to adherence,
and completed questionnaires on past traumatic events/stressors, disclosure,
depression, substance use, treatment self-efficacy, and social support.
Biomedical data were retrieved from existing medical records. Multivariate
logistic regression was performed to identify factors independently associated
with self-reported ART adherence (7 day recall). RESULTS: The mean age of
participants (SD) was 14.5 (2) years and 290 (56%) were female. Of the 519
participants, 153 (30%) reported having missed ART doses within the past week,
and 234 (45%) in the past month. Commonly reported barriers to adherence included
forgetting (39%), travel from home (14%), busy with other things (11%), feeling
depressed/overwhelmed (6%), feeling stigmatized by people outside (5%) and within
the home (3%). Factors found to be independently associated with missing a dose
in the past week were drinking alcohol in the past month (OR 4.96, 95% CI [1.41
17.4]), missed clinic appointment in the past 6 months (OR 2.23, 95% CI [1.43
3.49]), witnessed or experienced violence in the home (OR 1.86, 95% CI [1.08
3.21]), and poor treatment self-efficacy (OR 1.55 95% CI [1.02-2.34]). Sex and
age were not associated with adherence. CONCLUSION: In our study, nearly half of
all ALHIV reported non-adherence to ART in the past month. Violence in the home
or alcohol use in the past year as well as poor treatment self-efficacy were
associated with worse adherence. Sub-optimal adherence is a major issue for ALHIV
and compromise treatment outcomes. Programmes specifically tailored to address
those challenges most pertinent to ALHIV may help improve adherence to ART.
PMID- 28406276
TI - World Health Day focus on HIV and depression - a comorbidity with specific
challenges.
PMID- 28406274
TI - Barriers and facilitators to HIV testing among young men who have sex with men
and transgender women in Kingston, Jamaica: a qualitative study.
AB - INTRODUCTION: Young men who have sex with men (MSM) in Jamaica have the highest
HIV prevalence in the Caribbean. There is little information about HIV among
transgender women in Jamaica, who are also overrepresented in the Caribbean
epidemic. HIV-related stigma is a barrier to HIV testing among Jamaica's general
population, yet little is known of MSM and transgender women's HIV testing
experiences in Jamaica. We explored perceived barriers and facilitators to HIV
testing among young MSM and transgender women in Kingston, Jamaica. METHODS: We
implemented a community-based research project in collaboration with HIV and
lesbian, gay, bisexual and transgender (LGBT) agencies in Kingston. We held two
focus groups, one with young (aged 18-30 years) transgender women (n = 8) and one
with young MSM (n = 10). We conducted 53 in-depth individual semi-structured
interviews focused on HIV testing experiences with young MSM (n = 20),
transgender women (n = 20), and community-based key informants (n = 13). We
conducted thematic analysis to identify, analyze, and report themes. RESULTS:
Participant narratives revealed social-ecological barriers and facilitators to
HIV testing. Barriers included healthcare provider mistreatment, confidentiality
breaches, and HIV-related stigma: these spanned interpersonal, community and
structural levels. Healthcare provider discrimination and judgment in HIV testing
provision presented barriers to accessing HIV services (e.g. treatment), and
resulted in participants hiding their sexual orientation and/or gender identity.
Confidentiality concerns included: clinic physical arrangements that segregated
HIV testing from other health services, fear that healthcare providers would
publicly disclose their status, and concerns at LGBT-friendly clinics that peers
would discover they were getting tested. HIV-related stigma contributed to fear
of testing HIV-positive; this intersected with the stigma of HIV as a "gay"
disease. Participants also anticipated healthcare provider mistreatment if they
tested HIV positive. Participants identified individual (belief in benefits of
knowing one's HIV status), social (social support) and structural (accessible
testing) factors that can increase HIV testing uptake. CONCLUSION: Findings
suggest the need for policy and practice changes to enhance confidentiality and
reduce discrimination in Jamaica. Interventions to challenge HIV-related and LGBT
stigma in community and healthcare settings can enhance access to the HIV
prevention cascade among MSM and transgender youth in Jamaica.
PMID- 28406277
TI - The Blood Supply and Men Who Have Sex with Men.
PMID- 28406278
TI - Cardiac CT: a coming of age.
PMID- 28406279
TI - Update on the clinical utility of coronary computed tomographic angiography in
stable angina pectoris.
AB - Over the last decade, coronary computed tomographic angiography (CCTA) has
emerged as a valuable non-invasive imaging modality with excellent diagnostic
performance compared to invasive coronary angiography (ICA) for identifying
patients with coronary artery disease (CAD). Beyond the diagnosis of CAD, CCTA
also provides valuable prognostic information. While patients with normal CCTA
have excellent long-term prognosis, among those with CAD, increasing CAD extent
and severity is associated with increased cardiovascular event risk over both
medium- and long-term follow-up in both men and women. The ability to image non
obstructive CAD is a particularly unique attribute of CCTA. Moreover, the ability
to assess plaque features on CCTA has further enhanced our understanding of
coronary plaque dynamics and the prediction of future cardiovascular events. The
clinical impact of CCTA has been recently evaluated in two landmark prospective
multicenter trials, which have provided insights into the influence of CCTA on
the clinical management of symptomatic patients with suspected CAD. We review the
value of CCTA in the evaluation of patients with stable chest pain including its
diagnostic performance, prognostic utility and real-world clinical application.
PMID- 28406280
TI - Ticagrelor versus Clopidogrel in Peripheral Artery Disease.
PMID- 28406281
TI - Arrhythmogenic Right Ventricular Cardiomyopathy.
PMID- 28406282
TI - Mechanisms, Pathophysiology, and Management of Obesity.
PMID- 28406283
TI - Mechanisms, Pathophysiology, and Management of Obesity.
PMID- 28406284
TI - Dependence of Organic Interlayer Diffusion on Glass-Transition Temperature in
OLEDs.
AB - Organic light-emitting diodes (OLEDs) are subject to thermal stress from Joule
heating and the external environment. In this work, neutron reflectometry (NR)
was used to probe the effect of heat on the morphology of thin three-layer
organic films comprising materials typically found in OLEDs. It was found that
layers within the films began to mix when heated to approximately 20 degrees C
above the glass-transition temperature (Tg) of the material with the lowest Tg.
Diffusion occurred when the material with the lowest Tg formed a supercooled
liquid, with the rates of interdiffusion of the materials depending on the
relative Tg's. If the supercooled liquid formed at a temperature significantly
lower than the Tg of the higher-Tg material in the adjacent layer, then pseudo
Fickian diffusion occurred. If the two Tg's were similar, then the two materials
can interdiffuse at similar rates. The type and extent of diffusion observed can
provide insight into and a partial explanation for the "burn in" often observed
for OLEDs. Photoluminescence measurements performed simultaneously with the NR
measurements showed that interdiffusion of the materials from the different
layers had a strong effect on the emission of the film, with quenching generally
observed. These results emphasize the importance of using thermally stable
materials in OLED devices to avoid film morphology changes.
PMID- 28406286
TI - Construction of Hierarchically One-Dimensional Core-Shell CNT@Microporous Carbon
by Covalent Bond-Induced Surface-Confined Cross-Linking for High-Performance
Supercapacitor.
AB - A covalent bond-induced surface-confined cross-linking is reported to construct
one-dimensional coaxial CNT@microporous carbon composite (CNT@micro-C).
Octaphenyl polyhedral oligomeric silsesquioxane (Ph-POSS) composed of eight
phenyls and a -Si8O12 cage was selected as precursor for microporous carbon. The
layer-by-layer cross-linking of phenyl anchored Ph-POSS on the surface of CNT;
after carbonization and etching of -Si8O12 cages, CNT@micro-C including CNT core
and microporous carbon shell was harvested. The thickness of microporous carbon
shell can be well tailored from 6.0 to 20.0 nm, and the surface area of CNT@micro
C can reach 1306 m2 g-1. CNT@micro-C combines the structural advantages of CNT
and microporous carbon, presenting large surface area, high electrical
conductivity, fast ion transfer speed, and short ion transfer distance. When used
as electrode material, CNT@micro-C reveals superior supercapacitive performance;
for example, its capacitance can reach 243 F g-1 at 0.5 A g-1 and slightly
decreases to 209 F g-1 at 10 A g-1, indicating a capacitance retention of 86%.
Even at a very high scan rate of 50 A g-1, a high capacitance of 177 F g-1 is
retained, giving a capacitance retention of 73%.
PMID- 28406287
TI - Preparation of Carbon Nanotubes/Manganese Dioxide Composite Catalyst with Fewer
Oxygen-Containing Groups for Li-O2 Batteries Using Polymerized Ionic Liquids as
Sacrifice Agent.
AB - Considering the significant influence of oxygen-containing groups on the surface
of carbon involved electrodes, a carbon nanotube (CNT)-based MnO2 composite
catalyst was synthesized following a facile method while using polymerized ionic
liquids (PIL) as sacrifice agent. Herein, the PIL (polymerized hydrophobic 1
vinyl-3-ethylimidazolium bis ((trifluoromethyl)sulfonyl)imide) wrapped CNTs were
prepared. The composite was applied to support MnO2 by the treatment of KMnO4
solution, taking advantage of the reaction between PIL and KMnO4, which excludes
or suppresses the oxidation of CNTs, and the as-synthesized material with fewer
oxygen-containing groups acted as a cathode catalyst for Li-O2 batteries,
directly avoiding the application of binders. The catalyst shows enhanced
activity compared to that of the samples without PIL, as verified by the lower
overpotential during discharging and charging (0.97 V at the current density of
100 mA g-1). Meanwhile, the performance parameters such as Coulombic efficiency
and rate capability were also improved for the Li-O2 battery utilizing this
catalyst. Further, the formation of confined Li2O2 particles could be responsible
for the reduction of charge potential of Li-O2 batteries due to the synergy
effect of the intrinsic catalytic activity of MnO2 and fewer oxygen functional
groups on the catalyst surface.
PMID- 28406288
TI - Tin(IV) Compounds with 2-C6F4PPh2 Substituents and Their Reactivity toward
Palladium(0): Formation of Tin-Palladium Complexes via Oxidative Addition.
AB - The tin(IV) compounds MexSn(2-C6F4PPh2)4-x (1, x = 1; 2, x = 2) and ClSn(2
C6F4PPh2)3 (3) were obtained from the reactions of 2-LiC6F4PPh2 with MeSnCl3
(3:1), Me2SnCl2 (2:1), or SnCl4 (3:1), respectively. The reactions of 2
LiC6F4PPh2 with SnCl4 in different stoichiometric ratios (4:1-1:1) gave 3 as the
main product. Compound Cl2Sn(2-C6F4PPh2)2 (4) was formed in the transmetalation
reaction of 3 and [AuCl(tht)] but could not be isolated. 1 and 2 react with
palladium(0) sources {[Pd(PPh3)4] and [Pd(allyl)Cp]} by the oxidative addition of
one of their Sn-CAryl bonds to palladium(0) with formation of the
heterobimetallic complexes [MeSn(MU-2-C6F4PPh2)2Pd(kappaC-2-C6F4PPh2)] (5) and
[Me2Sn(MU-2-C6F4PPh2)Pd(kappa2-2-C6F4PPh2)] (6) featuring Sn-Pd bonds. The
reaction of 3 with palladium(0) proceeds via the oxidative addition of the Sn-Cl
bond to palladium(0), thus furnishing the complex [Sn(MU-2-C6F4PPh2)3PdCl] (7)
featuring a Sn-Pd bond and a pentacoordinate Pd atom. Transmetalation of MexSn(2
C6F4PPh2)4-x (x = 1-3) with [Pd(allyl)Cl]2 gave MexClSn(2-C6F4PPh2)3-x and
[Pd(allyl)(MU-2-C6F4PPh2)]2. For x = 1, the compound MeClSn(2-C6F4PPh2)2
(generated in situ) reacted with another 1 equiv of [Pd(allyl)Cl]2 by the
oxidative addition of the Sn-Cl bond to palladium(0) and the reductive
elimination of allyl chloride, thus leading to [MeSn(MU-2-C6F4PPh2)2PdCl] (8).
The reductive elimination of allyl chloride was also observed in the reaction of
3 with [Pd(allyl)Cl]2, giving [Sn(MU-2-C6F4PPh2)3PdCl] (7). All compounds have
been characterized by means of multinuclear NMR spectroscopy, elemental analysis,
single-crystal X-ray diffraction, and selected compounds by 119Sn Mossbauer
spectroscopy. Computational analyses (natural localized molecular orbital
calculations) have provided insight into the Sn-Pd bonding of 5-8.
PMID- 28406289
TI - Phylogenomic Analysis of the Microviridin Biosynthetic Pathway Coupled with
Targeted Chemo-Enzymatic Synthesis Yields Potent Protease Inhibitors.
AB - Natural products and their semisynthetic derivatives are an important source of
drugs for the pharmaceutical industry. Bacteria are prolific producers of natural
products and encode a vast diversity of natural product biosynthetic gene
clusters. However, much of this diversity is inaccessible to natural product
discovery. Here, we use a combination of phylogenomic analysis of the
microviridin biosynthetic pathway and chemo-enzymatic synthesis of
bioinformatically predicted microviridins to yield new protease inhibitors.
Phylogenomic analysis demonstrated that microviridin biosynthetic gene clusters
occur across the bacterial domain and encode three distinct subtypes of precursor
peptides. Our analysis shed light on the evolution of microviridin biosynthesis
and enabled prioritization of their chemo-enzymatic production. Targeted one-pot
synthesis of four microviridins encoded by the cyanobacterium Cyanothece sp. PCC
7822 identified a set of novel and potent serine protease inhibitors, the most
active of which had an IC50 value of 21.5 nM. This study advances the genome
mining techniques available for natural product discovery and obviates the need
to culture bacteria.
PMID- 28406290
TI - Cooperative Catalysis at Metal-Sulfur Bonds.
AB - Cooperative catalysis has attracted tremendous attention in recent years,
emerging as a key strategy for the development of novel atom-economic and
environmentally more benign catalytic processes. In particular, Noyori-type
complexes with metal-nitrogen bonds have been extensively studied and evolved as
privileged catalysts in hydrogenation chemistry. In contrast, catalysts
containing metal-sulfur bonds as the reactive site are out of the ordinary,
despite their abundance in living systems, where they are assumed to play a key
role in biologically relevant processes. For instance, the heterolysis of
dihydrogen catalyzed by [NiFe] hydrogenase is likely to proceed through
cooperative H-H bond splitting at a polar nickel-sulfur bond. This Account
provides an overview of reported metal-sulfur complexes that allow for
cooperative E-H bond (E = H, Si, and B) activation and highlights the potential
of this motif in catalytic applications. In recent years, our contributions to
this research field have led to the development of a broad spectrum of
synthetically useful transformations catalyzed by cationic ruthenium(II) thiolate
complexes of type [(DmpS)Ru(PR3)]+BArF4- (DmpS = 2,6-dimesitylphenyl thiolate,
ArF = 3,5-bis(trifluoromethyl)phenyl). The tethered coordination mode of the
bulky 2,6-dimesitylphenyl thiolate ligand is crucial, stabilizing the
coordinatively unsaturated ruthenium atom and also preventing formation of
binuclear sulfur-bridged complexes. The ruthenium-sulfur bond of these complexes
combines Lewis acidity at the metal center and Lewis basicity at the adjacent
sulfur atom. This structural motif allows for reversible heterolytic splitting of
E-H bonds (E = H, Si, and B) across the polar ruthenium-sulfur bond, generating a
metal hydride and a sulfur-stabilized E+ cation. Hence, this activation mode
provides a new strategy to catalytically generate silicon and boron
electrophiles. After transfer of the electrophile to a Lewis-basic substrate, the
resulting neutral ruthenium(II) hydride can either act as a hydride donor
(reductant) or as a proton acceptor (Bronsted base); the latter scenario is
followed by dihydrogen release. On the basis of this concept, the tethered
ruthenium(II) thiolate complexes emerged as widely applicable catalysts for
various transformations, which can be categorized into (i) dehydrogenative
couplings [Si-C(sp2), Si-O, Si-N, and B-C(sp2)], (ii) chemoselective reductions
(hydrogenation and hydrosilylation), and (iii) hydrodefluorination reactions. All
reactions are promoted by a single catalyst motif through synergistic metal
sulfur interplay. The most prominent examples of these transformations are the
first catalytic protocols for the regioselective C-H silylation and borylation of
electron-rich heterocycles following a Friedel-Crafts mechanism.
PMID- 28406285
TI - Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for
Modulation of the Sympathetic Stress Response.
AB - Serotonin (5-HT) is an important neurotransmitter in the central nervous system
where it modulates circuits involved in mood, cognition, movement, arousal, and
autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5
HT signaling, and genetic variations in SERT are associated with various
disorders including depression, anxiety, and autism. This review focuses on the
role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction
is evident in patients with depression, anxiety, and other diseases linked to
serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice
or chronic pharmacological block) has been reported to augment the sympathetic
stress response. Alterations to serotonergic signaling in the CNS and thus
central drive to the peripheral sympathetic nervous system are presumed to
underlie this augmentation. Although less widely recognized, SERT is robustly
expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of
the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT
but accumulate small amounts by SERT-mediated uptake. Recent evidence
demonstrated that 5-HT1A receptors inhibit catecholamine secretion from adrenal
chromaffin cells via an atypical mechanism that does not involve modulation of
cellular excitability or voltage-gated Ca2+ channels. This raises the possibility
that the adrenal medulla is a previously unrecognized peripheral hub for
serotonergic control of the sympathetic stress response. As a framework for
future investigation, a model is proposed in which stress-evoked adrenal
catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.
PMID- 28406291
TI - Using Ligand-Induced Protein Chemical Shift Perturbations To Determine Protein
Ligand Structures.
AB - Protein chemical shift perturbations (CSPs), upon ligand binding, can be used to
refine the structure of a protein-ligand complex by comparing experimental CSPs
with calculated CSPs for any given set of structural coordinates. Herein, we
describe a fast and accurate methodology that opens up new opportunities for
improving the quality of protein-ligand complexes using nuclear magnetic
resonance (NMR)-based approaches by focusing on the effect of the ligand on the
protein. The new computational approach, 1H empirical chemical shift perturbation
(HECSP), has been developed to rapidly calculate ligand binding-induced 1H CSPs
in a protein. Given the dearth of experimental information by which a model could
be derived, we employed high-quality density functional theory (DFT) computations
using the automated fragmentation quantum mechanics/molecular mechanics approach
to derive a database of ligand-induced CSPs on a series of protein-ligand
complexes. Overall, the empirical HECSP model yielded correlation coefficients
between its predicted and DFT-computed values of 0.897 (1HA), 0.971 (1HN), and
0.945 (side chain 1H) with root-mean-square errors of 0.151 (1HA), 0.199 (1HN),
and 0.257 ppm (side chain 1H), respectively. Using the HECSP model, we developed
a scoring function (NMRScore_P). We describe two applications of NMRScore_P on
two complex systems and demonstrate that the method can distinguish native ligand
poses from decoys and refine protein-ligand complex structures. We provide
further refined models for both complexes, which satisfy the observed 1H CSPs in
experiments. In conclusion, HECSP coupled with NMRScore_P provides an accurate
and rapid platform by which protein-ligand complexes can be refined using NMR
derived information.
PMID- 28406292
TI - Functionalization of Metal-Organic Frameworks To Achieve Controllable
Wettability.
AB - The overall versatility of a material can be immensely expanded by the ability to
controllably tune its hydrophobicity. Herein we took advantage of steric bias to
demonstrate that tricarboxylate metal-organic frameworks (MOFs) can undergo
covalent postsynthetic modification to confer various degrees of hydrophobicity.
MOF copper 2-aminobenzene-1,3,5-tricarboxylate was modified with varying-length
aliphatic carbon chains. Unmodified Cu3(NH2BTC)2 degrades in minutes upon contact
with water, whereas modification as low as 14% results in powders that show
significantly enhanced hydrophobic character with contact angles up to 147
degrees . The modified material is capable of withstanding direct contact with
water for 30 min with no visual evidence of altered surface characteristics. A
linear relationship was observed between the length of the tethered chain and the
water contact angle. These results reveal a predictable method for achieving a
range of desirable sorption rates and highly controllable hydrophobic character.
This work thereby expands the possibilities of rationally modifying MOFs for a
plethora of target-specific applications.
PMID- 28406293
TI - N-Terminus Binding Preference for Either Tanshinone or Analogue in Both
Inhibition of Amyloid Aggregation and Disaggregation of Preformed Amyloid Fibrils
Toward Introducing a Kind of Novel Anti-Alzheimer Compounds.
AB - Amyloid-beta (Abeta40/Abeta42) peptide with a length of 40 or 42 residues is
naturally secreted as cleavage product of the amyloid precursor protein, and
formation of Abeta aggregates in a patient's brain is a hallmark of Alzheimer's
disease (AD). Therefore, disaggregation and disruption provide potential
therapeutic approaches to reduce, inhibit, and even reverse Abeta aggregation.
The disaggregation/inhibition effect of the inhibitors applies generally to both
Abeta40 and Abeta42 aggregations. Here we capture the atomic-level details of the
interaction between Abeta40/Abeta42 and either natural tanshinone compound TS1 or
its derivative TS0, and observe novel results by using molecular dynamics
simulations. We observe that the natural TS1 indeed inhibits the monomolecular
Abeta42 (mAbeta42) aggregation and disaggregates Abeta42 amyloid fibrils, being
in good agreement with the experimental results. TS1 is favorable to stabilize
mAbeta40 and even Abeta40 fibril, playing an opposite role to that in the Abeta42
counterpart, however. TS0 can inhibit the misfolding of either mAbeta40 or
mAbeta42 and disaggregate Abeta42 fibril but stabilize the Abeta40 fibril. Using
a combination of secondary structural analysis, MM-PBSA binding energy
calculations, and radial distribution functions computations, we find that both
TS0 and TS1, especially the former, prefer to bind at the charged residues within
disordered N-terminus with a scarce positive binding energy and disappear the
characteristic C-terminal bend region of Abeta42 fibril, as well as twist the
Abeta42 fibril seriously. It turns out to destabilize the Abeta42 fibril and
enable the conversion of U-shaped Abeta42 fibril from the onefold to the twofold
morphologies. The N-terminal binding preference helps us to identify N-terminal
region as the specific epitope for specific inhibitors/drugs (such as TS0 and
analogues), heralding unusual inhibition/disaggregation or stabilization
mechanisms, and offering an alternative direction in engineering new inhibitors
to treat AD.
PMID- 28406294
TI - Noninvasive Respiratory Metabolite Analysis Associated with Clinical Disease in
Cetaceans: A Deepwater Horizon Oil Spill Study.
AB - Health assessments of wild cetaceans can be challenging due to the difficulty of
gaining access to conventional diagnostic matrices of blood, serum and others.
While the noninvasive detection of metabolites in exhaled breath could
potentially help to address this problem, there exists a knowledge gap regarding
associations between known disease states and breath metabolite profiles in
cetaceans. This technology was applied to the largest marine oil spill in U.S.
history (The 2010 Deepwater Horizon oil spill in the Gulf of Mexico). An accurate
analysis was performed to test for associations between the exhaled breath
metabolome and sonographic lung abnormalities as well as hematological, serum
biochemical, and endocrine hormone parameters. Importantly, metabolites
consistent with chronic inflammation, such as products of lung epithelial
cellular breakdown and arachidonic acid cascade metabolites were associated with
sonographic evidence of lung consolidation. Exhaled breath condensate (EBC)
metabolite profiles also correlated with serum hormone concentrations (cortisol
and aldosterone), hepatobiliary enzyme levels, white blood cell counts, and iron
homeostasis. The correlations among breath metabolites and conventional health
measures suggest potential application of breath sampling for remotely assessing
health of wild cetaceans. This methodology may hold promise for large cetaceans
in the wild for which routine collection of blood and respiratory anomalies are
not currently feasible.
PMID- 28406295
TI - Synthon Approach to Structure Models for the Bayerite-Derived Layered Double
Hydroxides of Li and Al.
AB - The Br- ion intercalated layered double hydroxide (LDH) of Li and Al obtained
from the bayerite-Al(OH)3 precursor crystallizes in a structure different from
that of the gibbsite-Al(OH)3 derived counterpart. Additionally, it undergoes
temperature- and humidity-induced reversible interpolytype transformations. The
dehydrated LDH (T ~ 120 degrees C) adopts a structure of hexagonal symmetry
(space group P31m) and comprises a stacking of the metal hydroxide layers
arranged one above another. On cooling and rehydration, the LDH adopts a
structure of monoclinic symmetry with a stepwise increase in the stacking angle,
beta. Using the structural synthon approach, based on the systematic elimination
of the principal symmetry elements of the hexagonal crystal, structure models
were generated for each of the two hydration steps (relative humidity ~50%, >70%)
and the structures refined (space group C2/m). The refined structures show that
the interpolytype transitions are a result of rigid translations of successive
metal hydroxide layers relative to one another by translation vectors (1/6, 0, 1)
and (1/3, 0, 1), respectively.
PMID- 28406296
TI - Light-Mediated Atom Transfer Radical Polymerization of Semi-Fluorinated
(Meth)acrylates: Facile Access to Functional Materials.
AB - A highly efficient photomediated atom transfer radical polymerization protocol is
reported for semi-fluorinated acrylates and methacrylates. Use of the
commercially available solvent, 2-trifluoromethyl-2-propanol, optimally balances
monomer, polymer, and catalyst solubility while eliminating transesterification
as a detrimental side reaction. In the presence of UV irradiation and ppm
concentrations of copper(II) bromide and Me6-TREN (TREN = tris(2-aminoethyl
amine)), semi-fluorinated monomers with side chains containing between three and
21 fluorine atoms readily polymerize under controlled conditions. The resulting
polymers exhibit narrow molar mass distributions (D ~ 1.1) and high end group
fidelity, even at conversions greater than 95%. This level of control permits the
in situ generation of chain-end functional homopolymers and diblock copolymers,
providing facile access to semi-fluorinated macromolecules using a single
methodology with unprecedented monomer scope. The results disclosed herein should
create opportunities across a variety of fields that exploit fluorine-containing
polymers for tailored bulk, interfacial, and solution properties.
PMID- 28406297
TI - Binding Analysis of Some Classical Acetylcholinesterase Inhibitors: Insights for
a Rational Design Using Free Energy Perturbation Method Calculations with QM/MM
MD Simulations.
AB - In the present study, the binding free energy of some classical inhibitors (DMT,
DNP, GNT, HUP, THA) with acetylcholinesterase (AChE) is calculated by means of
the free energy perturbation (FEP) method based on hybrid quantum mechanics and
molecular mechanics (QM/MM) potentials. The results highlight the key role of the
van der Waals interaction for the inhibition process, since the contribution of
this term to the binding free energy is almost as decisive as the electrostatic
one. The analysis of the geometrical parameters and the interaction energy per
residue along the QM/MM molecular dynamics (MD) simulations highlights the most
relevant interactions in the different AChE-ligand systems, showing that the
charged residues with a more prominent contribution to the interaction energy are
Asp72 and Glu199, although the relative importance depends on the molecular size
of the ligand. A correlation between the binding free energy and the number of
cation-pi interactions present in the systems has been established, DMT being the
most potent inhibitor, capable of forming four cation-pi interactions. A layer of
water molecules surrounding the inhibitors has been observed, which act as
bridges along a network formed by the ligands and the residues of the gorge and
also between different residues. Although several hydrogen bonds between ligands
and AChE do appear, no significant values of BIEs have been recorded. This
behavior can be accounted for by the special features of AChE, such as the
presence of several subsites of different natures in the gorge or the existence
of several water molecules that act as bridges in the electrostatic interactions.
PMID- 28406298
TI - Reaction of Aniline with Singlet Oxygen (O21Deltag).
AB - Dissolved organic matter (DOM) acts as an effective photochemical sensitizer that
produces the singlet delta state of molecular oxygen (O21Deltag), a powerful
oxidizer that removes aniline from aqueous solutions. However, the exact mode of
this reaction, the p- to o-iminobenzoquinone ratio, and the selectivity of one
over the other remain largely speculative. This contribution resolves these
uncertainties. We report, for the first time, a comprehensive mechanistic and
kinetic account of the oxidation of aniline with the singlet delta oxygen using
B3LYP and M06 functionals in both gas and aqueous phases. Reaction mechanisms
have been mapped out at E, H, and G scales. The 1,4-cycloaddition of O21Deltag to
aniline forms a 1,4-peroxide intermediate (M1), which isomerizes via a closed
shell mechanism to generate a p-iminobenzoquinone molecule. On the other hand,
the O21Deltag ene-type reaction forms an o-iminobenzoquinone product when the
hydroperoxyl bond breaks, splitting hydroxyl from the 1,2-hydroperoxide (M3)
moiety. The gas-phase model predicts the formation of both p- and o
iminobenzoquinones. In the latter model, the M1 adduct displays the selectivity
of up to 96%. A water-solvation model predicts that M1 decomposes further,
forming only p-iminobenzoquinone with a rate constant of k = 1.85 * 109 (L/(mol
s)) at T = 313 K. These results corroborate the recent experimental findings of
product concentration profile in which p-iminobenzoquinonine represents the only
detected product.
PMID- 28406299
TI - Discovery and Optimization of Isoquinoline Ethyl Ureas as Antibacterial Agents.
AB - Our strategy to combat resistant bacteria consisted of targeting the GyrB/ParE
ATP-binding sites located on bacterial DNA gyrase and topoisomerase IV and not
utilized by marketed antibiotics. Screening around the minimal ethyl urea binding
motif led to the identification of isoquinoline ethyl urea 13 as a promising
starting point for fragment evolution. The optimization was guided by structure
based design and focused on antibacterial activity in vitro and in vivo,
culminating in the discovery of unprecedented substituents able to interact with
conserved residues within the ATP-binding site. A detailed characterization of
the lead compound highlighted the potential for treatment of the problematic
fluoroquinolone-resistant MRSA, VRE, and S. pneumoniae, and the possibility to
offer patients an intravenous-to-oral switch therapy was supported by the
identification of a suitable prodrug concept. Eventually, hERG K-channel block
was identified as the main limitation of this chemical series, and efforts toward
its minimization are reported.
PMID- 28406301
TI - Interaction Entropy for Computational Alanine Scanning.
AB - The theoretical calculation of protein-protein binding free energy is a grand
challenge in computational biology. Accurate prediction of critical residues
along with their specific and quantitative contributions to protein-protein
binding free energy is extremely helpful to reveal binding mechanisms and
identify drug-like molecules that alter protein-protein interactions. In this
paper, we propose an interaction entropy approach combined with the molecular
mechanics/generalized Born surface area (MM/GBSA) method for solvation to compute
residue-specific protein-protein binding free energy. In the current approach,
the entropic loss in binding free energy of individual residues is explicitly
computed from moledular dynamics (MD) simulation by using the interaction entropy
method. In this approach the entropic contribution to binding free energy is
determined from fluctuation of the interaction in MD simulation. Studies for an
extensive set of realistic protein-protein interaction systems showed that by
including the entropic contribution, the computed residue-specific binding free
energies are in better agreement with the corresponding experimental data.
PMID- 28406300
TI - Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase
Inhibitors with Antibacterial Activity against Gram-Negative Bacteria.
AB - There is an urgent unmet medical need for novel antibiotics that are effective
against a broad range of bacterial species, especially multidrug resistant ones.
Tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase
and topoisomerase IV) display potent activity against Gram-positive pathogens and
no target-mediated cross-resistance with fluoroquinolones. We report our research
efforts aimed at expanding the antibacterial spectrum of this class of molecules
toward difficult-to-treat Gram-negative pathogens. Physicochemical properties
(polarity and basicity) were considered to guide the design process. Dibasic
tetrahydropyran-based compounds such as 6 and 21 are potent inhibitors of both
DNA gyrase and topoisomerase IV, displaying antibacterial activities against Gram
positive and Gram-negative pathogens (Staphylococcus aureus, Enterobacteriaceae,
Pseudomonas aeruginosa, and Acinetobacter baumannii). Compounds 6 and 21 are
efficacious in clinically relevant murine infection models.
PMID- 28406302
TI - Relativistic ab Initio Accurate Atomic Minimal Basis Sets: Quantitative LUMOs and
Oriented Quasi-Atomic Orbitals for the Elements Li-Xe.
AB - Valence virtual orbitals (VVOs) are a quantitative and basis set independent
method for extracting chemically meaningful lowest unoccupied molecular orbitals
(LUMOs). The VVOs are formed based on a singular value decomposition (SVD) with
respect to precomputed and internally stored ab initio accurate atomic minimal
basis sets (AAMBS) for the atoms. The occupied molecular orbitals and VVOs
together form a minimal basis set that can be transformed into orthogonal
oriented quasi-atomic orbitals (OQUAOs) that provide a quantitative description
of the bonding in a molecular environment. In the present work, relativistic
AAMBS are developed that span the full valence orbital space. The impact of using
full valence AAMBS for the formation of the VVOs and OQUAOs and the resulting
bonding analysis is demonstrated with applications to the cuprous chloride,
scandium monofluoride, and nickel silicide diatomic molecules.
PMID- 28406303
TI - Cp*Co(III)-Catalyzed C-H Functionalization Cascade of N-Methoxyamides with
Alkynedione for the Synthesis of Indolizidines.
AB - Cp*Co(III)-catalyzed C-H functionalization cascade of N-methoxyamides with
alkynedione has been reported for the synthesis of indolizidine scaffolds under
redox-neutral conditions. The reaction displays broad functional group tolerance
along with excellent yield. The reaction proceeds with kinetically relevant C-H
bond activation through carboxylate assistance with excellent
diastereoselectivity and complete opposite selectivity with respect to alkyne
insertion.
PMID- 28406304
TI - Dynamic Control of the Vortex Pinning Potential in a Superconductor Using Current
Injection through Nanoscale Patterns.
AB - Control over the vortex potential at the nanoscale in a superconductor is a
subject of great interest for both fundamental and technological reasons. Many
methods for achieving artificial pinning centers have been demonstrated, for
example, with magnetic nanostructures or engineered imperfections, yielding many
intriguing effects. However, these pinning mechanisms do not offer dynamic
control over the strength of the patterned vortex potential because they involve
static nanostructures created in or near the superconductor. Dynamic control has
been achieved with scanning probe methods on the single vortex level but these
are difficult so scale up. Here, we show that by applying controllable
nanopatterned current injection, the superconductor can be locally driven out of
equilibrium, creating an artificial vortex potential that can be tuned by the
magnitude of the injected current, yielding a unique vortex channeling effect.
PMID- 28406305
TI - An Organic Intermolecular Dehydrogenative Annulation Reaction.
AB - The discovery of a direct method for the synthesis of three-ring heterocyclic
carbazoles from unactivated arenes and anilides by a metal-free (organic)
intermolecular dehydrogenative annulation reaction under ambient laboratory
conditions is reported. Iodine(III) was used as the sole reagent either
stoichiometrically from inexpensive phenyliodine diacetate or organocatalytically
by in situ generation from PhI-mCPBA. In a single step, three C(sp2)-H bonds and
one N(sp3)-H bond are functionalized from two different arenes for tandem C-C and
C-N bond formation reactions.
PMID- 28406306
TI - Chiral Diphosphine-Palladium-Catalyzed Sequential Asymmetric Double-Friedel
Crafts Alkylation and N-Hemiketalization for Spiro-polycyclic Indole Derivatives.
AB - An efficient cascade asymmetric Friedel-Crafts alkylation/N
hemiketalization/Friedel-Crafts alkylation reaction of 3-alkylindoles with
oxindolyl beta,gamma-unsaturated alpha-ketoesters has been developed in the
presence of a chiral diphosphine-palladium(II) catalyst. A series of
enantiomerically enriched spiro-polycyclic indole derivatives have been
constructed in high yields with excellent enantioselectivities and
diastereoselectivities.
PMID- 28406307
TI - gamma-Cyclodextrin as a Catalyst for the Synthesis of 2-Methyl-3,5
diarylisoxazolidines in Water.
AB - A green and efficient 1,3-dipolar cycloaddition of nitrones with different
styrenes and cinnamates using a catalytic amount of gamma-cyclodextrin (gamma-CD)
in water has been developed to give substituted isoxazolidines. gamma-CD was
found to be highly efficacious in carrying out this reaction under an eco
friendly environment, affording moderate to excellent yields and, in some cases,
excellent diastereomeric excess (up to >95%) at 100 degrees C in 8-12 h. The
catalyst can be easily recuperated and recycled for several times without loss of
activity. Water, an eco-friendly reaction medium, has been utilized for the first
time, to the best of our knowledge, in this reaction. The credit of the presented
protocol includes high yields and catalyst reusability, and precludes the use of
organic solvents. The use of in silico calculations allowed us to rationalize the
obtained results and to improve the stereoselectivity.
PMID- 28406308
TI - Magnon Mode Selective Spin Transport in Compensated Ferrimagnets.
AB - We investigate the generation of magnonic thermal spin currents and their mode
selective spin transport across interfaces in insulating, compensated
ferrimagnet/normal metal bilayer systems. The spin Seebeck effect signal exhibits
a nonmonotonic temperature dependence with two sign changes of the detected
voltage signals. Using different ferrimagnetic garnets, we demonstrate the
universality of the observed complex temperature dependence of the spin Seebeck
effect. To understand its origin, we systematically vary the interface between
the ferrimagnetic garnet and the metallic layer, and by using different metal
layers we establish that interface effects play a dominating role. They do not
only modify the magnitude of the spin Seebeck effect signal but in particular
also alter its temperature dependence. By varying the temperature, we can select
the dominating magnon mode and we analyze our results to reveal the mode
selective interface transmission probabilities for different magnon modes and
interfaces. The comparison of selected systems reveals semiquantitative details
of the interfacial coupling depending on the materials involved, supported by the
obtained field dependence of the signal.
PMID- 28406309
TI - Direct Observation of Impurity Segregation at Dislocation Cores in an Ionic
Crystal.
AB - Dislocations, one-dimensional lattice defects, are known to strongly interact
with impurity atoms in a crystal. This interaction is generally explained on the
basis of the long-range strain field of the dislocation. In ionic crystals, the
impurity-dislocation interactions must be influenced by the electrostatic effect
in addition to the strain effect. However, such interactions have not been
verified yet. Here, we show a direct evidence of the electrostatic impurity
dislocation interaction in alpha-Al2O3 by visualizing the dopant atom
distributions at dislocation cores using atomic-resolution scanning transmission
electron microscopy (STEM). It was found that the dopant segregation behaviors
strongly depend on the kind of elements, and their valence states are considered
to be a critical factor. The observed segregation behaviors cannot be explained
by the elastic interactions only, but can be successfully understood if the
electrostatic interactions are taken into account. The present findings will lead
to the precise and quantitative understanding of impurity induced dislocation
properties in many materials and devices.
PMID- 28406310
TI - Cobalt-Catalyzed Selective Synthesis of Isoquinolines Using Picolinamide as a
Traceless Directing Group.
AB - Picolinamide has first been employed as a traceless directing group for the
cobalt-catalyzed oxidative annulation of benzylamides with alkynes to synthesize
isoquinolines through C-H/N-H bonds activation. Oxygen is used as a terminal
oxidant. This protocol exhibits good functional group tolerance and excellent
regioselectivity. Both terminal and internal alkynes can be efficiently applied
to this catalytic system as substrates.
PMID- 28406311
TI - Organocatalytic Asymmetric Decarboxylative Amination of beta-Keto Acids: Access
to Optically Active alpha-Amino Ketones and 1,2-Amino Alcohols.
AB - An organocatalytic asymmetric decarboxylative amination reaction of beta-keto
acids is described. Under mild reaction conditions, a series of chiral alpha
amino ketones were obtained in good to high yields (up to 99%) and
enantioselectivities (up to 95% ee). A chiral 1,2-amino alcohol was synthesized
from the corresponding decarboxylative amination product in several steps without
loss of enantioselectivity.
PMID- 28406312
TI - Repeatability of graph theoretical metrics derived from resting-state functional
networks in paediatric epilepsy patients.
AB - OBJECTIVE: To measure the repeatability of metrics that quantify brain network
architecture derived from resting-state functional MRI in a cohort of paediatric
patients with epilepsy. METHODS: We identified patients with: (1) epilepsy; (2)
brain MRI at 3 T; (3) two identical resting-state functional MRI acquisitions
performed on the same day. Undirected, weighted networks were constructed based
on the resting-state time series using a range of processing parameters including
parcellation size and graph threshold. The following topological properties were
calculated: degree, strength, characteristic path length, global efficiency,
clustering coefficient, modularity and small worldness. Based on repeated
measures, we then calculated: (1) Pearson correlation coefficient; (2) intraclass
correlation coefficient; (3) root-mean-square coefficient of variation; (4)
repeatability coefficient; and (5) 95% confidence limits for change. RESULTS: 26
patients were included (age range: 4-21 years). Correlation coefficients
demonstrated a highly consistent relationship between repeated observations for
all metrics, and the intraclass correlation coefficients were generally in the
excellent range. Repeatability in the data set was not significantly influenced
by parcellation size. However, trends towards decreased repeatability were
observed at higher graph thresholds. CONCLUSION: These findings demonstrate the
reliability of network metrics in a cohort of paediatric patients with epilepsy.
Advances in knowledge: Our results point to the potential for graph theoretical
analyses of resting-state data to provide reliable markers of network
architecture in children with epilepsy. At the level of an individual patient,
change over time greater than the repeatability coefficient or 95% confidence
limits for change is unlikely to be related to intrinsic variability of the
method.
PMID- 28406313
TI - High-dose vitamin D supplementation is associated with an improvement in several
cardio-metabolic risk factors in adolescent girls: a nine-week follow-up study.
AB - Background Vitamin D deficiency is a prevalent and important global health
problem. Because of its role in growth and development, vitamin D status is
likely to be particularly important in adolescent girls. Here, we explored the
effects of high-dose vitamin D supplementation on cardio-metabolic risk factors.
Methods We have examined the effects of vitamin D supplementation on cardio
metabolic risk factors in 988 healthy adolescent girls in Iran. Fasting blood
samples and anthropometric measurements were obtained at baseline and after
supplementation with high-dose vitamin D. All individuals took a capsule of
50,000 IU vitamin D/week for nine weeks. The study was completed by 940
participants. Results The prevalence of vitamin D deficiency was 90% at baseline,
reducing to 16.3% after vitamin D supplementation. Vitamin supplementation was
associated with a significant increase in serum concentrations of 25 (OH) vitamin
D and calcium. There were significant reductions in diastolic blood pressure,
heart rate, waist circumference and serum fasting blood glucose, total- and low
density lipoprotein-cholesterol after the nine-week period on vitamin D
treatment, but no significant effects were observed on body mass index, systolic
blood pressure or serum high-density lipoprotein cholesterol and triglyceride.
Conclusion Vitamin D supplementation had beneficial effects on cardio-metabolic
profile in adolescent girls.
PMID- 28406314
TI - Depletion of biotin using streptavidin-coated microparticles: a validated
solution to the problem of biotin interference in streptavidin-biotin
immunoassays.
AB - Background Biotin interference in streptavidin-based immunoassays causes
widespread analytical distortions that may lead to clinical confusion,
inappropriate patient management and, ultimately, adverse events. Its prevalence
has increased recently due to the increased use of high-dose biotin therapy in
specific patient groups (notably multiple sclerosis) and possibly the general
community. Methods We have developed a method to deplete biotin from samples
using the streptavidin-coated magnetic microparticles that are a component of
most susceptible assays. Results We show that high concentrations of spiked
biotin can be adequately depleted from serum using this approach, and that gross
biochemical derangements can be restored to normality. We also show that biotin
in samples derived from multiple sclerosis patients receiving 300 mg biotin daily
can be adequately depleted to remove associated analytical interference and
restore normal results. The method is applicable to competitive and sandwich
immunoassays and importantly, because it does not change the volume of the
sample, suitable for the measurement of free thyroid hormone assays. Application
of the method does not significantly change the precision of measurement, and for
the majority of analytes, the accuracy is not substantially altered. Conclusions
Adopting this method enables laboratories to confirm biotin interference in the
appropriate clinical setting. Moreover, it enables laboratories to remove the
interference and report accurate and reliable results, without the need for
patients to withhold beneficial therapy prior to blood tests. Until the biotin
tolerance of susceptible assays is improved, our method gives laboratories a safe
alternative for reporting results using streptavidin-based methods.
PMID- 28406316
TI - Five-year follow-up of persons with brain injury entering the French vocational
and social rehabilitation programme UEROS: Return-to-work, life satisfaction,
psychosocial and community integration.
AB - BACKGROUND: Social and vocational reintegration of persons with brain injury is
an important element in their rehabilitation. AIMS: To evaluate the 5-year
outcome of persons with brain injury included in 2008 in the Aquitaine Unit for
Evaluation, Training and Social and Vocational Counselling programme (UEROS).
METHOD: 57 persons with brain injury were recruited from those who completed the
2008 UEROS programme. Five years later, an interview was done to assess family
and vocational status, autonomy and life satisfaction. These results were
compared with those from persons completing the 1997-1999 programme. RESULTS: The
typical person entered the 2008 UEROS programme 6 years after a severe brain
injury (42%) and was male, single and 35 years. At the 5-year follow-up, more
persons lived with a partner (+23%) and lived in their own home (+21%). 47% were
working vs 11% on entering the programme. Approximately half were satisfied or
very satisfied with their quality of life. Having a job in 2013 was associated
with a high education level, less cognitive sequelae, having a job in 2008 and no
health condition. CONCLUSIONS: The UEROS programme is effective with regard to
return-to-work and improvement of autonomy in persons with brain injury,
irrespective of length of time from injury.
PMID- 28406317
TI - The Influence of Everyday Interpersonal Communication on the Medical Encounter:
An Extension of Street's Ecological Model.
AB - Street's ecological model has shaped the research-examining communication during
medical encounters for over a decade. Although the model accounts for the variety
of contexts that shape the conversations in which patients and health-care
providers engage, the model does not adequately address the way that everyday
conversations about health carry over into patient-provider interactions. In this
essay, we propose an extension of Street's model that adds the context of
everyday communication about health as a contributing factor in the medical
encounter. We support the need for this extension by discussing research that
points to the ways these conversations with our social network influence
communication during the medical encounter and propose new areas for research
based on this extension.
PMID- 28406315
TI - Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in
hepatic cancer model for neutron capture therapy.
AB - OBJECTIVE: Boron neutron-capture therapy (BNCT) has been used to inhibit the
growth of various types of cancers. In this study, we developed a 10BSH-entrapped
water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier
for the possible application of BNCT in hepatocellular carcinoma treatment.
METHODS: We prepared the 10BSH-entrapped WOW emulsion using double emulsification
technique and then evaluated the delivery efficacy by performing biodistribution
experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy
seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto
University Research Reactor with an average thermal neutron fluence of 5 * 1012 n
cm-2. Morphological and pathological analyses were performed on Day 14 after
neutron irradiation. RESULTS: Biodistribution results have revealed that 10B
atoms delivery with WOW emulsion was superior compared with those using iodized
poppy-seed oil conventional emulsion. There was no dissemination in abdomen or
lung metastasis observed after neutron irradiation in the groups treated with
10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the
liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non
injected group. CONCLUSION: Tumour growth suppression and cancer-cell-killing
effect was observed from the morphological and pathological analyses of the 10BSH
entrapped WOW emulsion-injected group, indicating its feasibility to be applied
as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The
results of the current study have shown that entrapped 10BSH has the potential to
increase the range of therapies available for hepatocellular carcinoma which is
considered to be one of the most difficult tumours to cure.
PMID- 28406318
TI - A low-dose and an ultra-low-dose contrast agent protocol for coronary CT
angiography in a clinical setting: quantitative and qualitative comparison to a
standard dose protocol.
AB - OBJECTIVE: To evaluate the impact of a low-dose (LD) and an ultra-LD (ULD)
contrast protocol for coronary CT angiography on qualitative and quantitative
image parameters in a clinical setting. METHODS: We scanned 120 consecutive
patients with a 256-slice CT scanner applying a LD (60 patients, 35-55 ml) or ULD
(60 patients, 25-45 ml) contrast protocol adapted to the body mass index.
Visually assessed image quality and attenuation measured in each coronary segment
were retrospectively compared in 20 consecutive patients scanned with a normal
dose (ND, 40-105 ml) contrast protocol. RESULTS: Visually assessed image quality
did not differ significantly among protocols. By contrast, attenuation obtained
from the ULD protocol (median contrast volume 35 ml) differed significantly from
the LD (median 45 ml) and ND (median 70 ml) protocols in the coronary segments
(316 +/- 52 vs 363 +/- 60 and 359 +/- 52 HU, p < 0.001). Attenuation did not
differ significantly between the LD and ND protocol. The proportion of patients
with inadequate coronary vessel attenuation was significantly higher (p < 0.001)
in the ULD protocol (37%) than in the ND (5%) and LD (10%) protocols but did not
differ significantly between the ND and LD protocols. CONCLUSION: In a clinical
setting, a LD contrast protocol with a median volume of 45 ml is feasible for the
latest generation 256-slice coronary CT angiography as it yields attenuation
comparable to a ND protocol. By contrast, the implementation of an ULD protocol
remains challenging. Advances in knowledge: Although not perceived by the naked
eye, an ULD contrast protocol in a clinical setting yields attenuation below a
threshold for diagnostic image quality.
PMID- 28406319
TI - Benralizumab as a potential treatment of asthma.
AB - INTRODUCTION: Current anti-inflammatory asthma therapies including inhaled
corticosteroids and leukotriene modifiers, are not always able to appropriately
control the disease and other approaches are needed. These therapies specific
target IgE (omalizumab) or IL-5 (mepolizumab). However, there is research
underway investigating interleukin-based monoclonal antibodies such as
benralizumab, an anti-IL-5R monoclonal antibody which is currently in phase III
clinical development. Areas covered: This review summarizes the existing
preclinical and clinical data of benralizumab. Data reviewed includes
benralizumab's efficacy and safety data. The author also provides their expert
opinion on this potential therapeutic and provide their perspectives for its
future development. Expert opinion: Benralizumab was able to interfere
significantly with disease-related morbidity and in particular with
hospitalizations due to asthma exacerbation rates in a subset of patients with
higher systemic eosinophil burden and higher doses of inhaled corticosteroids.
The sustained inhibitory effect on eosinophilic inflammation might be an
advantage which can be translated in less frequent dosing. Further attempts
should be made to better define the asthma endotype in which such an antibody
would be the most efficacious.
PMID- 28406320
TI - Underestimated impact of novel psychoactive substances: laboratory confirmation
of recreational drug toxicity in Oslo, Norway.
AB - CONTEXT: Recreational drug toxicity is frequent. Availability of new psychoactive
substances is steadily increasing. However, data with verified analyses from
clinical settings are limited. To evaluate the impact of novel psychoactive
substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed
samples from a selection of patients. METHODS: All the patients presenting with
recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic
(OAEOC) and at the Oslo University Hospital (OUH) were registered from April
through September 2014. Oral fluid samples were collected at the OAEOC. Blood
samples were collected at the OUH. The samples were screened using ultra-high
performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS).
RESULTS: Nine hundred and sixty-four cases were included, 841 (87.2%) at the
OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and
103 blood samples (OUH) could be analysed. NPS were not clinically suspected in
any of the screened cases. At the outpatient clinic, the most commonly found
substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55 (72.7%)
and heroin in 39/55 (70.9%). In seven (12.7%) cases NPS were detected: 4
methylamfetamine in three cases, dimethyltryptamine in two, methylone in one, and
N,N-dimethyl-3,4-methylenedioxyamfetamine in one. Among the hospital patients,
the most commonly found substances were clonazepam in 51/103 (49.5%) cases,
amfetamines in 48/103 (46.6%), heroin in 31/103 (30.1%), and diazepam in 30/103
(29.1%). In five (4.9%) cases NPS were detected: JWH-210 in two cases, AM-2201 in
two, and 5-EAPB in one. CONCLUSION: NPS were clinically not suspected, though
found in eight percent of cases. Still, the vast majority of patients treated for
recreational drug toxicity in Oslo have taken classical drugs. Management of
these patients should be based on their clinical condition. However, it is highly
important to be alert to atypical presentations possibly resulting from
unsuspected drugs.
PMID- 28406321
TI - "Am I also going to die, doctor?" A systematic review of the impact of in
hospital patients witnessing a resuscitation of another patient.
AB - BACKGROUND: There is a growing interest in the impact of family-witnessed
resuscitation. However, evidence about the effect of hospitalised patients
witnessing other patients' resuscitations is limited. AIM: The aim of this
systematic review is to explore the existing evidence related to the impact on
patients who witness resuscitation attempts on other patients in hospital
settings. METHODS: The databases BNI, CINAHL, EMBASE, MEDLINE and PsycINFO were
searched with the terms 'patient', 'inpatient', 'resuscitation', 'CPR',
'cardiopulmonary resuscitation' and 'witness'. The search strategy excluded the
terms 'out-of-hospital', 'family' and 'relative'. The inclusion criteria were:
studies related to patients exposed to a resuscitation attempt performed on
another patient; quantitative and qualitative design; and physiological or
psychological outcome measures. No limitations of date, language or settings were
applied. RESULTS: Five of the 540 identified studies were included: two
observational studies with control groups and three qualitative studies with
interviews and focus groups. Articles were published between 1968 and 2006 and
were mostly rated to have a low quality of evidence. Quantitative results of the
observational studies showed an increased heart rate in the study group
witnessing a resuscitation ( p = 0.05), increased systolic blood pressure ( p <
0.01) and increased anxiety ( p < 0.01). The qualitative studies highlighted the
coping strategies adopted by exposed patients in response to witnessing
resuscitation, including denial and dissociation. CONCLUSIONS: Our findings
suggest that patients may find witnessing resuscitation to be a stressful
experience. However, the evidence is sparse and mainly of poor quality. Further
research is needed in order to better understand the impacts of patients
witnessing a resuscitation of another patient and to identify effective support
systems.
PMID- 28406322
TI - Mass spectrometry-based proteomic exploration of the human immune system: focus
on the inflammasome, global protein secretion, and T cells.
AB - INTRODUCTION: The immune system is our defense system against microbial
infections and tissue injury, and understanding how it works in detail is
essential for developing drugs for different diseases. Mass spectrometry-based
proteomics can provide in-depth information on the molecular mechanisms involved
in immune responses. Areas covered: Summarized are the key immunology findings
obtained with MS-based proteomics in the past five years, with a focus on
inflammasome activation, global protein secretion, mucosal immunology,
immunopeptidome and T cells. Special focus is on extracellular vesicle-mediated
protein secretion and its role in immune responses. Expert commentary: Proteomics
is an essential part of modern omics-scale immunology research. To date, MS-based
proteomics has been used in immunology to study protein expression levels, their
subcellular localization, secretion, post-translational modifications, and
interactions in immune cells upon activation by different stimuli. These studies
have made major contributions to understanding the molecular mechanisms involved
in innate and adaptive immune responses. New developments in proteomics offer
constantly novel possibilities for exploring the immune system. Examples of these
techniques include mass cytometry and different MS-based imaging approaches which
can be widely used in immunology.
PMID- 28406323
TI - The inhibiting effect of intravenous anesthesia on adrenal gland functions under
the sepsis condition.
AB - This study aims to explore the effect of intravenous anesthesia on the adrenal
gland functions of rats with sepsis as well as on their lungs and adrenal gland
tissues in order to provide a theoretical reference for the cure of sepsis.
Female Sprague Dawley (SD) rats were taken as the research objects in this study.
Venous channels of rats were constructed by catheterization through the external
jugular vein, and the cecal ligation and puncture technique was adopted to
duplicate the sepsis rat models. The level of tumor necrosis factor-alpha (TNF
alpha) in serum was detected using enzyme-linked immunosorbent assay (ELISA), and
necrocytosis was observed by the fluorescent staining method. The results showed
that the survival rates of groups A, B, C, and D were 100%, 60%, 60%, and 50%,
respectively, while their concentrations of TNF-alpha in serum were101.26 +/-
43.38, 1398.68 +/- 178.56, 451.16 +/- 78.68, and 649.83 +/- 98.56 pg/mL,
respectively. Results of fluorescent staining showed that the number of living
cells per unit view in group A was 1428 +/- 166 and those of groups B, C and D
were 175 +/- 56, 618 +/- 76, and 468 +/- 55, respectively. Besides, it was found
that changes of inflammatory pathology of lung tissues of each group were
significant. In conclusion, etomidate does not affect the survival of sepsis rats
and does not exacerbate lung tissue inflammation in sepsis rats. Instead, it can
inhibit TNF-alpha in serum of sepsis rats, as well as the apoptosis of adrenal
cells in sepsis rats.
PMID- 28406324
TI - Evolving paradigm of treatment for autoimmune hepatitis.
AB - INTRODUCTION: Current medications for autoimmune hepatitis have broad anti
inflammatory and immunosuppressive actions, and their effects are short-lived and
inconsistent. The goals of this review were to describe the actions and
shortcomings of these medications, indicate the key pathogenic mechanisms that
might be targeted by site-directed interventions, and present the pivotal studies
supporting development of these alternative agents. Areas covered: Abstracts
cited in PubMed from April 1964 to February 2017 were identified using the search
words 'treatment of autoimmune hepatitis'. A secondary bibliography was developed
from the references cited in selected articles, and additional searches were
performed to expand the concepts developed in these articles. The number of
abstracts reviewed exceeded 1000, and the number of full-length articles reviewed
exceeded 100. Expert commentary: Molecular, cellular, and pharmacological
interventions that target key pathogenic pathways promise to change the current
paradigm of treatment for autoimmune hepatitis. Interventions affecting
lymphocyte activation, lymphocyte differentiation, effector cell migration,
hepatocyte apoptosis, oxidative-nitrosative stress, fibrogenesis, and intestinal
dysbiosis promise to emerge as supplemental or replacement therapies. The
intestinal microbiome constitutes the next investigational frontier that may
influence future management strategies. Unwanted and unexpected consequences of
manipulating these homeostatic pathways constitute the major unmeasured risks of
these evolving regimens.
PMID- 28406325
TI - Akinetic mutism in a patient with mild traumatic brain injury: A diffusion tensor
tractography study.
AB - OBJECTIVES: Akinetic mutism (AM) is characterized by a complete absence of
spontaneous behaviour and speech. We report on a patient with AM associated with
injury of the prefronto-caudate tract and prefronto-thalamic tract following mild
traumatic brain injury (TBI), diffusion tensor tractography (DTT). CASE
PRESENTATION: A 20-year-old man suffered from TBI resulting from a pedestrian car
accident. Following the TBI, he developed abulia (decreased activity and speech)
that worsened over approximately a year. His typical features of AM that remained
stable from one year until two years after the TBI are: he showed no spontaneous
movement or speech and remained recumbent with no spontaneous activity. RESULTS:
On one-month DTT, the neural connectivity of the caudate nucleus to the medial
prefrontal cortex was low in both hemispheres, and this neural connectivity was
lower on two-year DTT. The orbitofrontal-thalamic tract was thin in the left
hemisphere on one-month DTT, whereas this tract became thinner in both
hemispheres on two-year DTT. CONCLUSIONS: Using serial DTTs, injuries of the
prefronto-caudate tract and orbitofrontal-thalamic tract and degeneration of
these injured neural tracts concurrent with aggravation of abulia to AM were
demonstrated in a patient with mild TBI. ABBREVIATIONS AM akinetic mutism; BA
Brodmann areas; CN caudate nucleus; CST corticospinal tract; CRT
corticoreticulospinal tract; DTT diffusion tensor tractography; FAC Functional
Ambulation Category; PFC prefrontal cortex; MMSE Mini-Mental State Examination;
ROI region of interest; TBI traumatic brain injury.
PMID- 28406326
TI - Umeclidinium for the treatment of uncontrolled asthma.
AB - INTRODUCTION: Smooth muscle cell contraction in the airways is the principal
therapeutic target in asthmatic subjects and its insufficient treatment is often
a cause of uncontrolled disease. For this reason, research has focused on
targeting smooth muscle activity with anticholinergic agents, including
umeclidinium. Areas covered: This review highlights the potential application of
umeclidinium, a long acting muscarinic antagonist, as a novel therapeutic
approach for patients with severe uncontrolled asthma, despite maximal therapy.
Expert opinion: Umeclidinium, similarly to tiotropium, which has been recently
included in guidelines, may act by contrasting cholinergic activation in airways,
preventing or at least reducing smooth muscle cells contraction and the
consequent bronchoconstriction. This is similar to what occurs in chronic
obstructive pulmonary disease, for which umeclidinium has been regularly
approved. However, available data is not sufficient and further studies are
needed before regulatory approval can be sought, since only phase II clinical
trials have been conducted at present. Both quality of life and objectifiable
clinical data and parameters must be assessed, including lung function
improvements, reduction of exacerbations and reduction of as required
medications.
PMID- 28406327
TI - Key updates in the clinical application of electroconvulsive therapy.
AB - ECT is the oldest and most effective therapy available for the treatment of
severe major depression. It is highly effective in individuals with treatment
resistance and when a rapid response is required. However, ECT is associated with
memory impairment that is the most concerning side-effect of the treatment,
substantially contributing to the controversy and stigmatization surrounding this
highly effective treatment. There is overwhelming evidence for the efficacy and
safety of an acute course of ECT for the treatment of a severe major depressive
episode, as reflected by the recent FDA advisory panel recommendation to
reclassify ECT devices from Class III to the lower risk category Class II.
However, its application for other indications remains controversial, despite
strong evidence to the contrary. This article reviews the indication of ECT for
major depression, as well as for other conditions, including catatonia, mania,
and acute episodes of schizophrenia. This study also reviews the growing evidence
supporting the use of maintenance ECT to prevent relapse after an acute
successful course of treatment. Although ECT is administered uncommonly to
patients under the age of 18, the evidence supporting its use is also reviewed in
this patient population. Finally, memory loss associated with ECT and efforts at
more effectively monitoring and reducing it are reviewed.
PMID- 28406328
TI - Effects of education and income on cardiovascular outcomes: A systematic review
and meta-analysis.
AB - Objective Previous studies have reported discrepancy effects of education and
income on cardiovascular diseases. This systematic review and meta-analysis was
therefore conducted which aimed to summarize effects of education and income on
cardiovascular diseases. Methods Studies were identified from Medline and Scopus
until July 2016. Cohorts were eligible if they assessed associations between
education/income and cardiovascular diseases, had at least one outcome including
coronary artery diseases, cardiovascular events, strokes and cardiovascular
deaths. A multivariate meta-analysis was applied to pool risk effects of these
social determinants. Results Among 72 included cohorts, 39, 19, and 14 were
studied in Europe, USA, and Asia. Pooled risk ratios of low and medium versus
high education were 1.36 (95% confidence interval: 1.11-1.66) and 1.21 (1.06
1.40) for coronary artery diseases, 1.50 (1.17-1.92) and 1.27 (1.09-1.48) for
cardiovascular events, 1.23 (1.06-1.43) and 1.17 (1.01-1.35) for strokes, and
1.39 (1.26-1.54) and 1.21 (1.12-1.30) for cardiovascular deaths. The effects of
education on all cardiovascular diseases were still present in US and Europe
settings, except in Asia this was present only for cardiovascular deaths. Effects
of low and medium income versus high on these corresponding cardiovascular
diseases were 1.49 (1.16-1.91) and 1.27 (1.10-1.47) for coronary artery diseases,
1.17 (0.96-1.44) and 1.05 (0.98-1.13) for cardiovascular events, 1.30 (0.99-1.72)
and 1.24 (1.00-1.53) for strokes, and 1.76 (1.45-2.14) and 1.34 (1.17-1.54) for
cardiovascular deaths. Conclusion Social determinants are risk factors of
cardiovascular diseases in developed countries, although high heterogeneity in
pooling. Data in Asia countries are still needed to update pooling.
PMID- 28406329
TI - CIEMTO: the new drug and poison research and information center in Medellin,
Colombia.
PMID- 28406330
TI - Precarity and Preparedness: Non-Adherence as Institutional Work in Diagnosing and
Treating Malaria in Uganda.
AB - Access to anti-malarial drugs is increasingly governed by novel regulation
technologies like rapid diagnostic tests (RDTs). However, high rates of non
adherence particularly to negative RDT results have been reported, threatening
the cost-effectiveness of the two interrelated goals of improving diagnosis and
reducing the over-prescription of expensive anti-malarial drugs. Below I set out
to reconstruct prior treatment forms like presumptive treatment of malaria by
paying particular attention to their institutional groundings. I show how novel
regulation technologies affect existing institutions of care and argue that the
institutional work of presumptive treatment goes beyond the diagnosis and
treatment of a currently observed fever episode. Instead, in contexts of
precarity, through what I will call "practices of preparedness," presumptive
treatment includes a variety of practices, performances, temporalities, and
opportunities that allow individuals to prepare for future episodes of fever.
PMID- 28406331
TI - Treatment options for diabetic foot osteomyelitis.
AB - INTRODUCTION: Diabetic foot osteomyelitis therapeutical options are based on
antibiotic therapy and surgical resection of the infected bone(s). Surgical and
medical approaches of patients suffering from a diabetic foot osteomyelitis do
not oppose but are complementary and need to be discussed as a tailored manner.
Areas covered: The aim of the present article is to discuss data issued from the
most recent guidelines of the Infectious Diseases Society of America and the
International Working Group on the Diabetic Foot on the management of the
diabetic foot infection and from a search in the current literature using the
terms diabetic foot osteomyelitis and treatment/therapy/therapeutical in both
PubMed and Medline, restricted to the last five years. Expert opinion: Surgical
removal of the entire infected bone(s) has been considered in the past as the
standard treatment but medical approach of these patients has now proven efficacy
in selected situations. The current emergence of bacteria, especially among Gram
negative rods, resistant to almost all the available antibiotics gradually
augments the complexity of the management of these patients and is likely to
decrease the place of the medical approach and to worsen the outcome of these
infections in the next future.
PMID- 28406332
TI - Development of an eye-tracking method to assess mental set switching in people
with aphasia.
AB - BACKGROUND: Deficits in cognitive flexibility contribute to impaired functional
communication in people with aphasia. Understanding the relationship between
functional communication and cognitive flexibility in people with neurologic
communication disorders is important. However, traditional methods to assess
mental set switching pose significant linguistic, cognitive and motoric response
confounds. Eye-tracking methods have great potential to address these challenges.
AIMS: The goal of this study was to develop and validate an eye-tracking method
to index mental set switching in individuals without neurological impairment
based upon performance on a nonlinguistic switching task. METHODS: Eye movements
of 20 adults without communication disorders were recorded as they completed a
switching task, requiring participants to match stimuli to one or two search
criteria (colour or shape) in single- and mixed-task conditions. Differences
between single and mixed conditions were assessed with eye-tracking measures.
Performance on the eye-tracking task was compared to standardized measures of
cognitive flexibility. RESULTS: Eye-tracking measures indexed significant
differences between nonswitch and switch trials within and between single- and
mixed-task condition. Some standardized assessment measures correlated
significantly with the eye movement measures. CONCLUSIONS: Results support the
construct validity of the novel eye-tracking method for assessing cognitive
switching in language-normal adults. Clinical and research implications are
discussed.
PMID- 28406334
TI - The need for active surveillance for low risk prostate cancer.
PMID- 28406335
TI - Clinical efficacy of edaravone for the treatment of amyotrophic lateral
sclerosis.
AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal,
neurodegenerative disease. Although the pathogenesis remains unresolved,
oxidative stress is known to play a pivotal role. Edaravone works in the central
nervous system as a potent scavenger of oxygen radicals. In ALS mouse models,
edaravone suppresses motor functional decline and nitration of tyrosine residues
in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II
open-label trial, and two phase III placebo-control randomized trials were
reviewed. In all trials, the primary outcome measure was the changes in scores on
the revised ALS functional rating scale (ALSFRS-R) to evaluate motor function of
patients. Expert opinion: The phase II open label trial suggested that edaravone
is safe and effective in ALS, markedly reducing 3-nitrotyrosine levels in the
cerebrospinal fluid. One of the two randomized controlled trials showed
beneficial effects in ALSFRS-R, although the differences were not significant.
The last trial demonstrated that edaravone provided significant efficacy in
ALSFRS-R scores over 24 weeks where concomitant use of riluzole was permitted.
Eligibility was restricted to patients with a relatively short disease duration
and preserved vital capacity. Therefore, combination therapy with edaravone and
riluzole should be considered earlier.
PMID- 28406333
TI - Eat, breathe, ROS: controlling stem cell fate through metabolism.
AB - INTRODUCTION: Research reveals cardiac regeneration exists at levels previously
deemed unattainable. Clinical trials using stem cells demonstrate promising
cardiomyogenic and regenerative potential but insufficient contractile recovery.
Incomplete understanding of the biology of administered cells likely contributes
to inconsistent patient outcomes. Metabolism is a core component of many well
characterized stem cell types, and metabolic changes fundamentally alter stem
cell fate from self-renewal to lineage commitment, and vice versa. However, the
metabolism of stem cells currently studied for cardiac regeneration remains
incompletely understood. Areas covered: Key metabolic features of stem cells are
reviewed and unique stem cell metabolic characteristics are discussed. Metabolic
changes altering stem cell fate are considered from quiescence and self-renewal
to lineage commitment. Key metabolic concepts are applied toward examining
cardiac regeneration through stem cell-based approaches, and clinical
implications of current cell therapies are evaluated to identify potential areas
of improvement. Expert commentary: The metabolism and biology of stem cells used
for cardiac therapy remain poorly characterized. A growing appreciation for the
fundamental relationship between stem cell functionality and metabolic phenotype
is developing. Future studies unraveling links between cardiac stem cell
metabolism and regenerative potential may considerably improve treatment
strategies and therapeutic outcomes.
PMID- 28406336
TI - Intrajejunal levodopa infusion therapy for Parkinson's disease: practical and
pragmatic tips for successful maintenance of therapy.
AB - INTRODUCTION: Intrajejunal levodopa infusion (IJLI) therapy is one of the most
influential therapies in moderate to late stage Parkinson's disease with
documented effects on motor and nonmotor symptoms and quality of life. The
process of initiation and maintenance of therapy however, remains a challenge
particularly in the long term. Areas covered: The authors reviewed 'evidence
base' for pathways and advice given to patients pre and post IJLI initiation. The
authors found lack of patient, carer and clinician led 'real life' advisory
documents which need to be given to patients on IJLI. Expert commentary:
Experience from centers engaged in IJLI therapy as well as feedback from carers
and patients on IJLI suggest wide variability of practical advice given to
patients. This is important as such tips could avoid termination of treatment or
serious adverse events in some cases. In this review the authors provide a
collection of pragmatic and practical tips for patients initiated on IJLI, both
related to the short and long term and which we believe is a key unmet need. The
paper is illustrated with two case reports.
PMID- 28406337
TI - Inhaled Corticosteroid Use in Chronic Obstructive Pulmonary Disease and Risk of
Pneumonia: A Nested Case-Control Population-based Study in Lazio (Italy)-The
OUTPUL Study.
AB - Inhaled corticosteroid (ICS) use in chronic obstructive pulmonary disease (COPD)
patients is associated with a reduction of exacerbations and a potential risk of
pneumonia. The objective was to determine if ICS use, with or without long-acting
beta2-agonist, increases pneumonia risk in COPD patients. A cohort study was
performed using linked hospital and drug prescription databases in the Lazio
region. Patients (45+) discharged with COPD in 2006-2009 were enrolled and
followed from cohort entry until first admission for pneumonia, death or study
end, 31 December, 2012. A nested case-control approach was used to estimate the
rate ratio (RR) associated with current or past use of ICS adjusted for age,
gender, number of exacerbations in the previous year and co-morbidities. Current
users were defined as patients with their last ICS prescribed in the 60 days
prior to the event. Past users were those with the last prescription between 61
and 365 days before the event. Current use was classified into three levels
(high, medium, low) according to the medication possession ratio. Among the
cohort of 19288 patients, 3141 had an event of pneumonia (incidence rate for
current use 87/1000py, past use 32/1000py). After adjustment, patients with
current use were 2.29 (95% confidence interval [CI]: 1.99-2.63) times more likely
to be hospitalised for pneumonia with respect to no use; for past use RR was 1.23
(95% CI: 1.07-1.42). For older patients (80+), the rate was higher than that for
younger patients. ICS use was associated with an excess risk of pneumonia. The
effect was greatest for higher doses and in the very elderly.
PMID- 28406338
TI - Increased kallistatin levels in patients with obesity and prediabetes compared to
normal glucose tolerance.
AB - PURPOSE: Kallistatin is a member of serine protease inhibitors (SERPIN) family,
which has various functions such as regulation of cardiovascular function and
blood vessels development. Its levels are elevated in patients with type 1 and
type 2 diabetes with chronic diabetic complications. The aim of the present study
was to compare serum kallistatin levels between obese subjects with prediabetes
and with normal glucose tolerance. METHODS: In this study we included 80 subjects
at mean age of 50.4 +/- 10.6 years, divided into two age and BMI-matched groups -
group 1 with obesity without glycemic disturbances (n = 41) and group 2 with
obesity and prediabetes (n = 39). Oral glucose tolerance test with measurement of
immunoreactive insulin was performed in all participants and levels of
kallistatin were measured using ELISA method. RESULTS: We found significantly
higher levels of kallistatin in patients with prediabetes compared to controls
(data are presented as median (min; max) because data were not normally
distributed) (6.3 (4.4; 9.0) vs. 5.6 (3.1; 8.7) ng/ml; p = 0.022) and in patients
with metabolic syndrome compared to those without (6.0 (4.9; 9.0) vs. 5.5 (3.1;
7.7); p = 0.006), but the levels were similar in patients with and without
insulin resistance. CONCLUSIONS: The levels of kallistatin are higher in
individuals with prediabetes, but are similar in subjects with and without
insulin resistance, which indicates that the main factor for its increased levels
may be hyperglycemia and not insulin sensitivity state.
PMID- 28406339
TI - A case study of healthcare providers' goals during interprofessional rounds.
AB - Daily interprofessional rounds enhance collaboration among healthcare providers
and improve hospital performance measures. However, it is unclear how healthcare
providers' goals influence the processes and outcomes of interprofessional
rounds. The purpose of this case study was to explore the goals of healthcare
providers attending interprofessional rounds in an internal medicine ward. The
second purpose was to explore the challenges encountered by healthcare providers
while pursuing these goals. Three focus groups were held with healthcare
providers of diverse professional backgrounds. Focus group field notes and
transcripts were analysed using thematic analysis. The data indicated that there
was no consensus among healthcare providers regarding the goals of
interprofessional rounds. Discharge planning and patient care delivery were
perceived as competing priorities during rounds, which limited the participation
of healthcare providers. Nevertheless, study participants identified goals of
rounds that were relevant to most care providers: developing shared perspectives
of patients through direct communication, promoting collaborative decision
making, coordinating care, and strengthening interprofessional relationships.
Challenges in achieving the goals of interprofessional rounds included
inconsistent attendance, exchange of irrelevant information, variable
participation by healthcare providers, and inconsistent leadership. The findings
of this study underscore the importance of shared goals in the context of
interprofessional rounding.
PMID- 28406340
TI - Team functioning in hospice interprofessional meetings: An exploratory study of
providers' perspectives.
AB - Interprofessional collaboration is the foundation of hospice service delivery. In
the United States, hospice agencies are required to regularly convene
interprofessional meetings during which teams review plans of care for the
patients and families they serve. A small body of research suggests that team
functioning could be significantly enhanced in hospice interprofessional
meetings; however, systematic investigation of this possibility has been limited
to date. The purpose of this qualitative study was to better understand the
experiences and perspectives of hospice providers who regularly participate in
interprofessional meetings as a first step toward improving teamwork in this
setting. We interviewed 24 hospice providers and conducted a template analysis of
qualitative data to identify barriers and facilitators to effective team
functioning in interprofessional meetings. Participants recognised the ways
meetings supported high-quality, holistic patient and family care but voiced
frustrations over meeting inefficiencies, particularly in light of caseloads they
perceived as overly demanding. Time constraints were often viewed as prohibiting
the inclusion of interprofessional content and full participation of all team
members. Findings suggest that modifications to interprofessional meetings such
as standardising processes may enhance meeting efficiency and team functioning.
PMID- 28406341
TI - Outcomes of haematuria referrals: two-year data from a single large university
hospital in Denmark.
AB - OBJECTIVE: The aim of this study was to review haematuria referrals to a large
university hospital in Denmark, based on the previous Danish guidelines for
haematuria referral (before January 2016), to evaluate the pattern of referrals
and the cancer detection rates and compare these with the current guidelines.
MATERIALS AND METHODS: A retrospective study was undertaken of all patients
referred from primary care for the evaluation of haematuria from January 2013 to
December 2014. All patients underwent cystoscopic examination and upper urinary
tract evaluation using computed tomography. Patients' demographics, type of
haematuria, presence of urinary symptoms and cancer detection rates were
recorded. RESULTS: The study included 1577 patients, with a mean age of 63 years
(range 16-96 years). Of these, 56.4% had visible haematuria (VH) and 43.6% were
referred for non-visible haematuria (NVH). In total, 228 malignancies were
detected (14.5% cancer detection rate). Overall, 11.2% of patients had bladder
cancer, 1.8% renal cancer and 0.4% upper tract transitional cell carcinoma. In
the VH group, 205 malignancies were detected (23% cancer detection rate). The
detection rate was higher for those with asymptomatic VH (24.6%) than for those
with symptomatic VH (15.4%). The cancer detection rate for symptomatic NVH was
9.1%, with only three cancers diagnosed in those younger than 60 years of age.
For asymptomatic NVH, the cancer detection rate was only 1.5%, with a total of
eight urological malignancies diagnosed in patients aged 60 years or older.
CONCLUSIONS: The new Danish referral pathway has an acceptable capture rate for
patients presenting with haematuria of all severities. The overall cancer
detection rate of 14.5%, and 23% for patients with VH in this study, is an
important validation of previous studies. A cancer detection rate of greater than
30% was shown in patients with VH over 70 years old.
PMID- 28406342
TI - Modelling the effect of perceived interdependence among mental healthcare
professionals on their work role performance.
AB - The purpose of mental healthcare system reform was to enhance service efficiency
by strengthening primary mental healthcare and increasing service integration in
communities. Reinforcing interprofessional teamwork also intended to address the
extensive and multidimensional needs of patients with mental disorders by
bringing together a broader array of expertise. In this context, mental
healthcare professionals (MHCPs) from various health and social care professions
are more interdependent in many aspects of their work (tasks, resources, and
goals). We wanted to examine the effect of perceived interdependence among MHCPs
on their work role performance in the context of mental healthcare. For this
purpose, we developed and tested a model coherent with the Input-Mediator-Outcome
Input (IMOI) framework of team effectiveness. Data from questionnaires
administered to 315 MHCPs from four local health service networks in Quebec,
Canada were analysed through structural equation modelling and mediation
analysis. The structural equation model provided a good fit for the data and
explained 51% of the variance of work role performance. Perceived collaboration,
confidence in the advantages of interprofessional collaboration, involvement in
the decision process, knowledge sharing, and satisfaction with the nature of the
work partially mediated the effect of perceived interdependence among team
members on work role performance. Therefore, perceived interdependence among team
members had a positive impact on the work role performance of MHCPs mostly
through its effect on favourable team functioning features. This implies, in
practice, that increased interdependence of MHCPs would be more likely to truly
enhance work role performance if team-based interventions to promote
collaborative work and interprofessional teaching and training programs to
support work within interprofessional teams were jointly implemented.
Participation in the decision process and knowledge sharing should also be
fostered, for instance, by adopting knowledge management best practices.
PMID- 28406343
TI - Insights from native mass spectrometry approaches for top- and middle- level
characterization of site-specific antibody-drug conjugates.
AB - Antibody-drug conjugates (ADCs) have emerged as a family of compounds with
promise as efficient immunotherapies. First-generation ADCs were generated mostly
via reactions on either lysine side-chain amines or cysteine thiol groups after
reduction of the interchain disulfide bonds, resulting in heterogeneous
populations with a variable number of drug loads per antibody. To control the
position and the number of drug loads, new conjugation strategies aiming at the
generation of more homogeneous site-specific conjugates have been developed. We
report here the first multi-level characterization of a site-specific ADC by
state-of-the-art mass spectrometry (MS) methods, including native MS and its
hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS
methodologies for site-specific ADC analysis, with the unique ability to provide
several critical quality attributes within one single run, along with a direct
snapshot of ADC homogeneity/heterogeneity without extensive data interpretation.
The capabilities of native IM-MS to directly access site-specific ADC
conformational information are also highlighted. Finally, the potential of these
techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by
comparing the analytical characterization of a site-specific DAR4 ADC to that of
first-generation ADCs. Altogether, our results highlight the compatibility,
versatility, and benefits of native MS approaches for the analytical
characterization of all types of ADCs, including site-specific conjugates. Thus,
we envision integrating native MS and IM-MS approaches, even in their latest
state-of-the-art forms, into workflows that benchmark bioconjugation strategies.
PMID- 28406344
TI - Fabrication and evaluation of Eudragit(r) polymeric films for transdermal
delivery of piroxicam.
AB - The aims of this work were to develop and characterize the prolonged release
piroxicam transdermal patch as a prototype to substitute oral formulations, to
reduce side effects and improve patient compliance. The patches were composed of
film formers (Eudragit(r)) as a matrix backbone, with PVC as a backing membrane
and PEG200 used as a plasticizer. Results from X-ray diffraction patterns and
Fourier transform-infrared spectroscopy indicated that loading piroxicam into
films changed the drug crystallinity from needle to an amorphous or dissolved
form. Piroxicam films were prepared using Eudragit(r) RL100 and Eudragit(r) RS100
as film formers at various ratios from 1:0 to 1:3. Films prepared solely by
Eudragit(r) RL100 showed the toughest and softest film, while other formulations
containing Eudragit(r) RS100 were hard and brittle. Drug release kinetic data
from the films fitted with the Higuchi model, and the piroxicam release mechanism
was diffusion controlled. Among all formulation tested, Eudragit(r) RL100 films
showed the highest drug release rate and the highest drug permeation flux across
human epidermal membrane. Increasing drug loading led to an increase in drug
release rate. Eudragit(r) can be used as a film former for the fabrication of
piroxicam films.
PMID- 28406345
TI - Not Your Typical Alcohol Accord: The Long-Term Impact of a Voluntary Liquor
Agreement in a Small Australian Town.
AB - BACKGROUND: The town of Norseman introduced a Voluntary Liquor Agreement
(voluntary restrictions on alcohol sales) in 2008, to reduce problematic
drinking. This study examined its long-term impact. METHODS: Quantitative data on
alcohol (cask wine, fortified wine, spirits) wholesale sales, hospital emergency
visits and alcohol related offenses were compared from before to after the
introduction of the restrictions. Qualitative interview data were collected from
10 key informants and from focus groups with Indigenous residents. RESULTS:
Consumption of cask wine declined in the short and long term. Fortified wine
consumption did not change in the short term, but declined in the long term.
Spirit consumption did not change in the short term, but increased in the long
term. Total beverage consumption did not change at any time. There was no change
in hospital emergency visits. There was a decline in Indigenous and non
Indigenous burglary and assault offenses, and a decline in Indigenous domestic
violence. Police tasking (callouts) declined. Key informants and focus group
participants indicated the behavior of drinkers, alcohol consumption, alcohol
harms and community climate had all improved. CONCLUSIONS: These findings
indicate that alcohol restrictions, backed by the community, can have a long-term
impact on local alcohol problems.
PMID- 28406347
TI - Youth Problem Drinking: The Role of Parental and Familial Relationships.
AB - BACKGROUND: Alcohol use continues to be an important global public health problem
and adolescence seems to be a decisive period of time in the development of
drinking patterns into adulthood. While most studies concentrate on frequency and
amount of alcohol, fewer studies address "problem drinking." Gathering
information on youth's alcohol-related behavioral consequences is especially
important. OBJECTIVES: Current research focuses on gathering information on the
background of problem drinking behavior with special attention to
parental/familial relationships. METHODS: The survey was conducted within the
youth health behavior - Mako research project in 2012 (n = 1,981, aged 13-18
years, 50.9% males). Anonymous, self-administered questionnaires contained items
on sociodemographics, substance use, and parental/familial relationships (such as
parental control and awareness or variables of family environment). RESULTS:
Problem drinking (identified in 17.2% of the sample) was more common among males
and high school students and those from lower socioeconomic status groups
compared to their counterparts. Among the familial/parental variables, negative
family interactions, discussion of problems with parents, physical and sexual
abuse were positively related to adolescent problem drinking, whereas parental
control and awareness, and the positive identification with parents proved to be
protective factors. Conclusions/Importance: We conclude that parents and the
family were important correlates of adolescents' problem drinking. Our findings
suggest that on-going school interventions to prevent the development of problem
drinking among youth should include parents and the family.
PMID- 28406346
TI - A novel laparoscopic grasper with two parallel jaws capable of extracting the
mechanical behaviour of soft tissues.
AB - Data related to force-deformation behaviour of soft tissue plays an important
role in medical/surgical applications such as realistically modelling mechanical
behaviour of soft tissue as well as minimally invasive surgery (MIS) and medical
diagnosis. While the mechanical behaviour of soft tissue is very complex due to
its different constitutive components, some issues increase its complexity like
behavioural changes between the live and dead tissues. Indeed, an adequate
quantitative description of mechanical behaviour of soft tissues requires high
quality in vivo experimental data to be obtained and analysed. This paper
describes a novel laparoscopic grasper with two parallel jaws capable of
obtaining compressive force-deformation data related to mechanical behaviour of
soft tissues. This new laparoscopic grasper includes four sections as mechanical
hardware, sensory part, electrical/electronical part and data storage part. By
considering a unique design for mechanical hardware, data recording conditions
will be close to unconfined-compression-test conditions; so obtained data can be
properly used in extracting the mechanical behaviour of soft tissues. Also, the
other distinguishing feature of this new system is its applicability during
different laparoscopic surgeries and subsequently obtaining in vivo data.
However, more preclinical examinations are needed to evaluate the practicality of
the novel laparoscopic grasper with two parallel jaws.
PMID- 28406348
TI - Motivations for Using MDMA (Ecstasy/Molly) among African Americans: Implications
for Prevention and Harm-Reduction Programs.
AB - Despite the growing popularity of MDMA (ecstasy/molly) among African Americans,
their motives for using the drug are still largely unknown. The purpose of this
study was to identify and describe the most salient motivations for using MDMA
among this understudied population. In-depth interviews (n = 15) were conducted
with a sample of African American young adults in Southwest Florida between
August 2014 and November 2015. The primary motivations for using MDMA included:
(1) altering the effects of marijuana and alcohol; (2) lasting longer sexually;
(3) enhancing sexual pleasure; and (4) facilitating "freaky" sexual experiences.
This is the first study to directly examine MDMA motivations specifically among
African American drug users, and findings shed light on why some African
Americans use MDMA. A better understanding of why African Americans use this drug
should help to inform prevention and harm-reduction efforts. Study findings show
the need for health messages that include the potential consequences of mixing
MDMA with other drugs, and engaging in high-risk sexual behaviors after taking
MDMA. These data contrast with motivations (e.g., introspection, self
enlightenment, getting into the music) commonly reported among groups of largely
White MDMA users, suggesting that interventions tailored specifically for African
American users are needed.
PMID- 28406349
TI - The state of the art and future opportunities for using longitudinal n-of-1
methods in health behaviour research: a systematic literature overview.
AB - n-of-1 studies test hypotheses within individuals based on repeated measurement
of variables within the individual over time. Intra-individual effects may differ
from those found in between-participant studies. Using examples from a systematic
review of n-of-1 studies in health behaviour research, this article provides a
state of the art overview of the use of n-of-1 methods, organised according to
key methodological considerations related to n-of-1 design and analysis, and
describes future challenges and opportunities. A comprehensive search strategy
(PROSPERO:CRD42014007258) was used to identify articles published between 2000
and 2016, reporting observational or interventional n-of-1 studies with health
behaviour outcomes. Thirty-nine articles were identified which reported on n-of-1
observational designs and a range of n-of-1 interventional designs, including AB,
ABA, ABABA, alternating treatments, n-of-1 randomised controlled trial, multiple
baseline and changing criterion designs. Behaviours measured included treatment
adherence, physical activity, drug/alcohol use, sleep, smoking and eating
behaviour. Descriptive, visual or statistical analyses were used. We identify
scope and opportunities for using n-of-1 methods to answer key questions in
health behaviour research. n-of-1 methods provide the tools needed to help
advance theoretical knowledge and personalise/tailor health behaviour
interventions to individuals.
PMID- 28406350
TI - Clinical Field Supervision of EMS Providers.
PMID- 28406351
TI - Substance Use in Undergraduate Students With Histories of Attention
Deficit/Hyperactivity Disorder (ADHD): The Role of Impulsivity.
AB - BACKGROUND: Emerging adulthood (18-25 years old) is regarded as a time of
identity exploration that includes a peak in risky behaviors, such as substance
use and misuse. Attention-deficit/hyperactivity disorder (ADHD) is also
associated with greater levels of risky behaviors, including substance use and
misuse; however, there is a lack of research on substance use by emerging adults
with ADHD, in particular the potential mechanisms that may facilitate this risk.
OBJECTIVES: The present study builds on the existing research regarding the
association between ADHD and substance use by examining roles of multiple facets
of impulsivity in facilitating this association during emerging adulthood.
METHODS: In a sample of 197 undergraduate students (24 students with an ADHD
diagnostic history), we assessed for components of impulsivity (e.g., urgency,
sensation-seeking) and rates of alcohol abuse, tobacco use, cannabis use, illicit
drug use, and stimulant medication misuse within the past year. RESULTS: Findings
indicate that facets of impulsivity, as a whole, explained the association
between an ADHD diagnostic history and both illicit drug use and alcohol abuse
such that students with ADHD histories tended to report higher levels of
impulsivity, which increased risk of alcohol abuse and illicit drug use. Higher
levels of specific facets of impulsivity, particularly negative urgency, also
facilitated associations between having ADHD and engaging in most forms of
substance use tested herein. Conclusions/Importance: Specific facets of
impulsivity appear to be important mediators of the association between ADHD and
substance use, and should be considered as potential targets of substance use
interventions for this population.
PMID- 28406352
TI - Using low-dose homoharringtonine and cytarabine in combination with granulocyte
colony-stimulating factor in a priming induction therapy for acute myeloid
leukemia: a retrospective study of 29 cases in china.
PMID- 28406353
TI - The effect of the mindfulness-based transition to motherhood program in pregnant
women with preterm premature rupture of membranes.
AB - The purpose of the researchers is to determine the effect of a mindfulness
program on readiness for motherhood, the level of maternal attachment, and on
postpartum self-evaluation. We used a quasiexperimental design. Researchers
applied the mindfulness-based Transition to Motherhood program to the treatment
group for 7 days. Data were collected between December 2012 and June 2014 in
Turkey. At the end of the study, the treatment group showed improvement in
measures of acceptance of pregnancy, level of readiness to give birth, level of
maternal attachment, and level of competence in the role of motherhood.
PMID- 28406354
TI - Human endogenous retroviruses and multiple sclerosis: Causation, association, or
after-effect?
AB - From the early days of MS discovery, infections have been proposed as a possible
cause of the disease. In the last three decades, an association between human
endogenous retrovirus expression and MS has been further investigated and
confirmed. Nevertheless, the role of such retroviruses in the disease needs
clarification. In this review, we introduce MSRV/HERV-W and describe its
association with MS. We then summarize the evidence for the involvement of
MSRV/HERV-W in the aetiology and progression of MS and its possible role as
biomarker and drug target. Biological mechanisms for HERV effects in MS may
involve the activation of innate immune pathways by the envelope protein of MSRV
(MSRVEnv). In addition to in vitro and experimental studies, further insight on
how HERVs may influence immune-mediated pathology in MS may also come from the
use of antiretroviral treatments in patients.
PMID- 28406356
TI - The association between fundamental athletic movements and physical fitness in
elite junior Australian footballers.
AB - This study investigated the associations between fundamental athletic movement
and physical fitness in junior Australian football (AF). Forty-four under 18
players performed a fundamental athletic movement assessment consisting of an
overhead squat, double lunge, single leg Romanian deadlift and a push up.
Movements were scored on three assessment criterions using a three-point scale.
Additionally, participants performed five physical fitness tests commonly used
for talent identification in AF. A Spearman's nonparametric correlation matrix
was built, with correlation coefficients being visualised using a circularly
rendered correlogram. Score on the overhead squat was moderately positively
associated with dynamic vertical jump height on left (rs = 0.40; P <= 0.05) and
right (rs = 0.30; P <= 0.05) leg take-off, stationary vertical jump (rs = 0.32; P
<= 0.05) and negatively associated with 20-m sprint time (rs = -0.35; P <= 0.05).
Score on the double lunge (left/right side) was moderately positively associated
with the same physical fitness tests as well as score on the multistage fitness
test. Results suggest that improvements in physical fitness qualities may occur
through concurrent increases in fundamental athletic movement skill, namely the
overhead squat and double lunge movements. These findings may assist with the
identification and development of talent.
PMID- 28406357
TI - A survey of service providers' views on care and support provision for older
women from Black and minority ethnic backgrounds in Wales: Implications for
policy and practice.
AB - Drawing on quantitative data from a large study, we explored service providers'
perceptions of the care and support provided to older women from Black and
minority ethnic backgrounds living in the UK. Analyzing 102 responses to a
questionnaire, we found that the care needs of this group of older women were not
adequately addressed, with ineffective communication being frequently reported. A
number of information pathways and barriers to service provision were identified.
More work is needed to explore not only how best to acknowledge diversity in care
needs within older populations, but also to design and deliver responsive
services accordingly.
PMID- 28406358
TI - Bone health in elite Kenyan runners.
AB - Impact loading in athletes participating in various sports has been positively
associated with increased bone mineral density (BMD), but this has not been
investigated in elite Kenyan runners. Body composition and site-specific BMD
measures quantified with dual x-ray absorptiometry were measured in 15 elite male
Kenyan runners and 23 apparently healthy South African males of different
ethnicities. Training load and biomechanical variables associated with impact
loading, such as joint stiffness, were determined in the elite Kenyan runners.
Greater proximal femur (PF) BMD (g . cm-2) was higher (P = 0.001, ES = 1.24) in
the elite Kenyan runners compared with the controls. Six of the 15 (40%) Kenyan
runners exhibited lumbar spine (LS) Z-Scores below -2.0 SD, whereas this was not
found in the apparently healthy controls. PFBMD was associated with training load
(r = 0.560, P = 0.003) and ankle (r = 0.710, P = 0.004) and knee (r = 0.546, P =
0.043) joint stiffness. Elite Kenyan runners exhibit greater PFBMD than healthy
controls, which is associated with higher training load and higher joint
stiffness. Our results reaffirm the benefits of impact loading on BMD at a weight
bearing site, while a high prevalence of low LSBMD in the elite Kenyan runners is
hypothesised to be the result of a mismatch between energy intake and high
training load. Future research investigating energy availability in Kenyan
runners and the possible association with musculoskeletal injury should be
investigated.
PMID- 28406359
TI - Enantioselective analysis of chloramphenicol residues in honey samples by chiral
LC-MS/MS and results of a honey survey.
AB - Chloramphenicol (CAP) is a broad-spectrum antibiotic used widely in both human
and veterinary medication. Since 1994, CAP has not been authorised for use in
food-producing animals in the European Union due to several adverse effects. A
minimum required performance level (MRPL) of 0.3 ug kg-1 was established in 2003.
The CAP molecule contains two asymmetric centres, thus in total four para-CAP
stereoisomers exist. Only the RR-CAP enantiomer is bioactive, having significant
antimicrobial activity. For the first time a chiral LC-MS/MS method is reported
to identify and quantify the four CAP enantiomers at residue levels in honey
samples. The method was validated at two concentration levels. The decision
limits (CCalpha) and detection capabilities (CCbeta) were well below 0.3 ug kg-1,
with limits of quantification (LOQs) between 0.08 and 0.12 ug kg-1 for all four
enantiomers. The method provides a sensitive and reliable analysis of CAP
enantiomers in honey, and proved its robustness during the daily routine analyses
of numerous honey samples. In an internal honey survey, in total 40 honey samples
from different geographical regions with identified CAP residues at or above the
MRPL were reanalysed by chiral LC-MS/MS. In nine honey samples only the bioactive
RR-CAP was detected as anticipated. However, in all other 31 honey samples the
non-bioactive SS-CAP was also identified and quantified unambiguously. In 10 of
these samples, mixtures of RR- and SS-CAP were analysed, and in 21 samples only
the SS-CAP enantiomer, with concentrations up to 2.2 ug kg-1. Most of these
samples are honeys from Ukraine and Eastern Europe. This is the first report of
SS-CAP residues in food samples. The potential sources for these findings are
discussed and the need of further systematic studies emphasised. It is
recommended to examine in more depth the toxicological profile of the individual
CAP stereoisomers.
PMID- 28406360
TI - Comparing Alcohol Marketing and Alcohol Warning Message Policies Across Canada.
AB - BACKGROUND: In order to reduce harms from alcohol, evidence-based policies are to
be introduced and sustained. OBJECTIVES: To facilitate the dissemination of
policies that reduce alcohol-related harms by documenting, comparing, and sharing
information on effective alcohol polices related to restrictions on alcohol
marketing and alcohol warning messaging in 10 Canadian provinces. METHODS: Team
members developed measurable indicators to assess policies on (a) restrictions on
alcohol marketing, and (b) alcohol warning messaging. Indicators were peer
reviewed by three alcohol policy experts, refined, and data were collected,
submitted for validation by provincial experts, and scored independently by two
team members. RESULTS: The national average score was 52% for restrictions on
marketing policies and 18% for alcohol warning message policies. Most provinces
had marketing regulations that went beyond the federal guidelines with penalties
for violating marketing regulations. The provincial liquor boards' web pages
focused on product promotion, and there were few restrictions on sponsorship
activities. No province has implemented alcohol warning labels, and Ontario was
the sole province to have legislated warning signs at all points-of-sale. Most
provinces provided a variety of warning signs to be displayed voluntarily at
points-of-sale; however, the quality of messages varied. Conclusions/Importance:
There is extensive alcohol marketing with comparatively few messages focused on
the potential harms associated with alcohol. It is recommended that governments
collaborate with multiple stakeholders to maximize the preventive impact of
restrictions on alcohol marketing and advertising, and a broader implementation
of alcohol warning messages.
PMID- 28406362
TI - Evaluation of coverall field dry aerosol decontamination methods using a manikin.
AB - A full-size manikin dressed in fire-resistant coveralls coated in 120 g of sodium
bicarbonate was randomly given one of three treatments for dry aerosol
decontamination. The three treatments were high-efficiency particulate air (HEPA)
vacuum, a commercially available air shower, and the no treatment control.
Immediately after the treatment, the coveralls were doffed and an air sample was
taken in the breathing zone of the manikin to estimate airborne total and
respirable dust concentrations to an unprotected worker post decontamination.
Each treatment was applied four times for a total of 12 trials. Using analysis of
variance (ANOVA) with alpha =.05 and Tukey's Honestly Significant Difference
multiple comparison post-test, it was determined that HEPA vacuuming was not
significantly different from the air shower for respirable dust, but only the air
shower was significantly better than no decontamination (p =.037). For total
dust, HEPA was not significantly different from the air shower, but both were
significantly better than no treatment (p =.007, p =.004, respectively).
PMID- 28406361
TI - Predictors of performance in a 4-h mountain-bike race.
AB - This study aimed to cross validate previously developed predictive models of
mountain biking performance in a new cohort of mountain bikers during a 4-h event
(XC4H). Eight amateur XC4H cyclists completed a multidimensional assessment
battery including a power profile assessment that consisted of maximal efforts
between 6 and 600 s, maximal hand grip strength assessments, a video-based
decision-making test as well as a XC4H race. A multiple linear regression model
was found to predict XC4H performance with good accuracy (R2 = 0.99; P < 0.01).
This model consisted of [Formula: see text] relative to total cycling mass (body
mass including competition clothing and bicycle mass), maximum power output
sustained over 60 s relative to total cycling mass, peak left hand grip strength
and two-line decision-making score. Previous models for Olympic distance MTB
performance demonstrated merit (R2 = 0.93; P > 0.05) although subtle changes
improved the fit, significance and normal distribution of residuals within the
model (R2 = 0.99; P < 0.01), highlighting differences between the disciplines.
The high level of predictive accuracy of the new XC4H model further supports the
use of a multidimensional approach in predicting MTB performance. The difference
between the new, XC4H and previous Olympic MTB predictive models demonstrates
subtle differences in physiological requirements and performance predictors
between the two MTB disciplines.
PMID- 28406363
TI - Insurance Receipt and Readiness for Opportunities under the Affordable Care Act:
A National Survey of Treatment Providers for Substance Use Disorders.
AB - This study measures the readiness of substance use disorder (SUD) treatment to
use opportunities under the Affordable Care Act by examining Medicaid and private
insurance acceptance between 2011 and 2013, as well as center characteristics
associated with acceptance. Data for this study were from a random sample of SUD
treatment centers in the United States. Interviews were conducted on site and
face to face, with administrative and clinical directors. We employed logistic
regression analyses to examine Medicaid acceptance and private insurance
acceptance. We found that 59% of centers accepted Medicaid and 55% accepted
private insurance. Accredited centers were more likely to accept Medicaid. A 12
step orientation and greater reliance on female clients were negatively
associated with Medicaid acceptance. Larger centers and centers with a greater
percentage of counselors with advanced degrees had greater odds of accepting
private insurance. Centers that offered residential treatment had lower odds of
accepting either Medicaid or private insurance. For private insurance acceptance,
having a specific track for homeless patients lowered the odds of acceptance, as
did having a greater percentage of Hispanic clients. Newly insured individuals
under the ACA may have difficulty finding a program that accepts insurance.
Future research should examine effects of Medicaid expansion on SUD treatment
delivery.
PMID- 28406364
TI - Fume emissions from a low-cost 3-D printer with various filaments.
AB - 3-D printing is an additive manufacturing process involving the injection of
melted thermoplastic polymers, which are then laid down in layers to achieve a
pre-designed shape. The heated deposition process raises concerns of potential
aerosol and volatile organic compounds (VOC) emission and exposure. The
decreasing cost of desktop 3-D printers has made the use of 3-D printers more
acceptable in non-industrial workplaces lacking sufficient ventilation.
Meanwhile, little is known about the characteristics of 3-D printing fume
emission. The objective of this study was to characterize aerosols and VOC
emissions generated from various filaments used with a low-cost 3-D printer in an
environmental testing chamber. A pre-designed object was printed in 1.25 hours
using eight types of filaments. A scanning mobility particle sizer and an
aerodynamic particle sizer were employed to measure the particle size
distribution in sub-half-micron fraction (<0.5 um) and super-half-micron fraction
(0.5-20 um), respectively. VOC concentration was monitored real-time by a
photoionization detector and sampled with a tri-sorbent thermal desorption tube,
and analyzed by thermal desorption gas chromatography mass spectrometry (TD
GC/MS). Results showed high levels of fume particles emission rate (1.0 * 107 to
1.2 * 1010 #/min) in the sub-half-micron range with mode sizes of 41-83 nm.
Particle concentrations peaked during the heat-up and solid layer printing
periods. Total VOC concentration in the chamber followed a first-order buildup,
with predominant VOC species in the chamber were breakdown and reaction products
of the filaments, such as styrene from ABS filaments. These findings and exposure
scenario estimation suggest that although the VOC concentrations were much lower
than occupational exposure limits, particles with size less than micron might be
a concern for users of low-cost 3-D printers due to high respirablity, especially
if used in settings without proper guidance and engineering control.
PMID- 28406365
TI - Diagnosing and Resolving Conflict Created by Strategic Plans: Where Outreach
Strategies and Execution Meet at an Academic Health Center.
AB - The imperative for strategic change at academic health centers has never been
stronger. Underpinning the success of strategic change is an effective process to
implement a strategy. Healthcare organizations, however, often fail to execute on
strategy because they do not activate the requisite capabilities and management
processes. The University of Kentucky HealthCare recently defined its 2020
strategic plan to adapt to emerging market conditions. The authors outline the
strategic importance of strengthening partnership networks and the initial
challenges faced in executing their strategy. The findings are a case study in
how one academic health center has approached strategy implementation.
PMID- 28406366
TI - Detection of pathogenic bioaerosols and occupational risk in a Philippine
landfill site.
AB - Payatas landfill site is one of the major dumpsites in the Philippines. In this
study, the landfill was evaluated regarding the presence and concentration of
pathogenic bacterial aerosols through culture and molecular techniques.
Bioaerosols are biological airborne particles that may or may not cause diseases.
Active sampling was done using MAS-100 Air Sampler from both indoor and outdoor
locations. To test the accuracy of the culture method, those that were
presumptively identified as Staphylococcus aureus and Klebsiella pneumoniae were
subjected to molecular analysis using 16s rRNA sequencing, and as a result, they
were identified as different species. The exposure assessment done by interview
showed matches among prevalent diseases. The results of this study can be used as
a basis for creating standards and regulations for workers' and residents' safety
and health in the landfill site.
PMID- 28406367
TI - Issue-Relevant Values and Opinions About Gay Rights: Beyond Equality and
Morality.
AB - Although many studies have examined the role of values in shaping public opinion,
the number of values that inform this research is limited. This article employs
the concept of issue-relevant values as a means to explore the broader range of
values associated with policy issues. After discussing the concept in general
terms, the article explores issue-relevant values pertinent to public opinion
about gay rights. Using the policy examples of employment nondiscrimination and
same-sex couple adoption, the present study identifies, measures, and assesses
several values that add to the very short list previously used to explain public
opinion about gay rights issues. Content from interest-group Web sites and news
media coverage of the two issues aided in identifying the values. Data from an
original Internet survey yield valid measures of the values. Multivariate
analyses indicate that the values behave in predictable ways: they are strongly
influenced by partisanship, and they strongly affect opinions about the two
issues. The performance of the values is consistent with findings from previous
research on the partisan basis of values and the value-based nature of opinions.
The article concludes with suggestions for further empirical and theoretical work
that could apply and extend the concept of issue-relevant values.
PMID- 28406368
TI - PRN Medication Administration in a Geriatric Psychiatric Hospital: Chart Review
and Nursing Perspective.
AB - OBJECTIVE: To improve patient care/outcome, an evaluation was conducted of
nursing procedures and protocols for pro re nata (PRN) medications. METHODS: A 14
day chart review was conducted for 27 patients with mood and thought disorders
(MTD) and for 24 patients with organic disorders (OD) at a geriatric psychiatric
hospital, and a questionnaire was completed by 20 nurses. RESULTS: 377 PRNs were
administered to patients in the MTD and OD units (240 and 137, respectively). The
majority of PRNs were administered during the evening shifts on the MTD unit and
during the day shifts on the OD unit. Chart notes indicated the behavior
requiring PRN administration was not always specifically described and
therapeutic interventions were not often attempted before PRN administration.
Inconsistency between chart notes and medication record books was noted in the
majority of cases. It was often not known whether the PRN was initiated by the
staff, patient, or family. PRNs were reported to be not effective in the majority
of cases. CONCLUSIONS: Documentation was suboptimal and effectiveness was poor.
CLINICAL IMPLICATIONS: It would be worthwhile to train all staff in a patient
centered or ecopsychosocial (i.e., non-pharmacological) model of care, which
would provide staff alternatives to PRNs. In that context, it would be important
to implement standards of practice into geriatric psychiatry inpatient settings
for PRN administration and documentation.
PMID- 28406369
TI - Comparing Some Production Functions for Inpatient Health Services in Selected
Public Hospitals in Spain.
AB - To investigate the adequacy of the widely used Cobb-Douglas and transcendental
logarithmic (translog) models of the production functions of hospital inpatient
services, the authors fitted these and additive models to data for the four most
productive health services of 10 public hospitals in Galicia, Spain (the same
four in each). Production, measured as admissions weighted in accordance with
their diagnosis-related groups (DRGs), was treated as a function of physician
full-time equivalents as surrogate labor factor and number of beds as surrogate
capital factor. The results suggest that while the Cobb-Douglas and translog
models suffice to represent the production functions of services with low average
DRG weight, the greater flexibility of additive models is required for services
with higher average DRG weight when only these two inputs are considered.
PMID- 28406370
TI - Farmers Have Hearts: The Prevalence of Risk Factors for Cardiovascular Disease
Among a Subgroup of Irish Livestock Farmers.
AB - OBJECTIVES: Despite international findings that farmers have better health
outcomes than other occupation groups, Irish farmers are found to be a high-risk
group for cardiovascular disease (CVD). Early detection of CVD through preventive
health measurements, such as screening of high-risk groups, can contribute to a
reduction of CVD cases. Farmers, however, represent a "challenging" group in
terms of engaging in preventive health behaviors. This study examined the
prevalence of cardiovascular risk factors among male Irish livestock farmers who
participated in heart screening as part of a workplace health intervention.
METHODS: In this cross-sectional study, data were collected from a convenience
sample (N = 310) of farmers. Consent included permission to analyze the heart
screening results and to participate in two follow-up questionnaires by phone at
Week 1 (n = 224) and Week 12 (n = 172). All data were entered onto the
Statistical Package for the Social Sciences (SPSS version 22) and both
descriptive and inferential statistics were compiled. RESULTS: Almost one in two
(46%; n = 140) farmers had high blood pressure (>=140/>=90 mm Hg), and 46% (n =
140) had elevated total cholesterol. One third of farmers were found to be obese
(35%; n = 110). The vast majority (83%; n = 255) had at least four risk factors
for CVD based on the outcomes of the heart screening. CONCLUSION: The study
findings in relation to obesity and the prevalence of multiple risk factors for
CVD are a particular cause of concern and shed considerable light on the current
excess burden of CVD among farmers in Ireland.
PMID- 28406371
TI - Inhalation exposure during spray application and subsequent sanding of a wood
sealant containing zinc oxide nanoparticles.
AB - Nano-enabled construction products have entered into commerce. There are concerns
about the safety of manufactured nanomaterials, and exposure assessments are
needed for a more complete understanding of risk. This study assessed potential
inhalation exposure to ZnO nanoparticles during spray application and power
sanding of a commercially available wood sealant and evaluated the effectiveness
of local exhaust ventilation in reducing exposure. A tradesperson performed the
spraying and sanding inside an environmentally-controlled chamber. Dust control
methods during sanding were compared. Filter-based sampling, electron microscopy,
and real-time particle counters provided measures of exposure. Airborne
nanoparticles above background levels were detected by particle counters for all
exposure scenarios. Nanoparticle number concentrations and particle size
distributions were similar for sanding of treated versus untreated wood. Very few
unbound nanoparticles were detected in aerosol samples via electron microscopy,
rather nano-sized ZnO was contained within, or on the surface of larger airborne
particles. Whether the presence of nanoscale ZnO in these aerosols affects
toxicity merits further investigation. Mass-based exposure measurements were
below the NIOSH Recommended Exposure Limit for Zn, although there are no
established exposure limits for nanoscale ZnO. Local exhaust ventilation was
effective, reducing airborne nanoparticle number concentrations by up to 92% and
reducing personal exposure to total dust by at least 80% in terms of mass. Given
the discrepancies between the particle count data and electron microscopy
observations, the chemical identity of the airborne nanoparticles detected by the
particle counters remains uncertain. Prior studies attributed the main source of
nanoparticle emissions during sanding to copper nanoparticles generated from
electric sander motors. Potentially contrary results are presented suggesting the
sander motor may not have been the primary source of nanoparticle emissions in
this study. Further research is needed to understand potential risks faced by
construction workers exposed to mixed aerosols containing manufactured
nanomaterials. Until these risks are better understood, this study demonstrates
that engineering controls can reduce exposure to manufactured nanomaterials;
doing so may be prudent for protecting worker health.
PMID- 28406372
TI - Do Young Drivers Become Safer After Being Involved in a Collision?
AB - As drivers age, their risk of being involved in a car collision decreases. The
present study investigated if this trend is due, in part, to some risky drivers
having a collision early in their driving lives and subsequently reducing their
risky driving after that negative experience. Accelerometers and video cameras
were installed in the vehicles of 16- to 17-year-old drivers ( N = 254), allowing
coders to measure the number of g-force events (i.e., events in which a threshold
acceleration level was exceeded) per 1,000 miles and the number of collisions.
Among the 41 participants who experienced a severe collision, the rate of g-force
events dropped significantly in the 1st month after the collision, remained
unchanged for the 2nd month, and increased significantly in the 3rd month. There
were no changes in the rate of g-force events at comparable time points for the
drivers not involved in a collision. Being involved in a collision led to a
decrease in risky driving, but this may have been a temporary effect.
PMID- 28406373
TI - True Numerical Cognition in the Wild.
AB - Cognitive and neural research over the past few decades has produced
sophisticated models of the representations and algorithms underlying numerical
reasoning in humans and other animals. These models make precise predictions for
how humans and other animals should behave when faced with quantitative
decisions, yet primarily have been tested only in laboratory tasks. We used data
from wild baboons' troop movements recently reported by Strandburg-Peshkin,
Farine, Couzin, and Crofoot (2015) to compare a variety of models of quantitative
decision making. We found that the decisions made by these naturally behaving
wild animals rely specifically on numerical representations that have key
homologies with the psychophysics of human number representations. These findings
provide important new data on the types of problems human numerical cognition was
designed to solve and constitute the first robust evidence of true numerical
reasoning in wild animals.
PMID- 28406374
TI - Money May Buy Happiness, but Often So Little That It Doesn't Matter.
PMID- 28406375
TI - Who Dares, Who Errs? Disentangling Cognitive and Motivational Roots of Age
Differences in Decisions Under Risk.
AB - We separate for the first time the roles of cognitive and motivational factors in
shaping age differences in decision making under risk. Younger and older adults
completed gain, loss, and mixed-domain choice problems as well as measures of
cognitive functioning and affect. The older adults' decision quality was lower
than the younger adults' in the loss domain, and this age difference was
attributable to the older adults' lower cognitive abilities. In addition, the
older adults chose the more risky option more often than the younger adults in
the gain and mixed domains; this difference in risk aversion was attributable to
less pronounced negative affect among the older adults. Computational modeling
with a hierarchical Bayesian implementation of cumulative prospect theory
revealed that the older adults had higher response noise and more optimistic
decision weights for gains than did the younger adults. Moreover, the older
adults showed no loss aversion, a finding that supports a positivity-focus
(rather than a loss-prevention) view of motivational reorientation in older age.
PMID- 28406376
TI - Thinking Fast Increases Framing Effects in Risky Decision Making.
AB - Every day, people face snap decisions when time is a limiting factor. In
addition, the way a problem is presented can influence people's choices, which
creates what are known as framing effects. In this research, we explored how time
pressure interacts with framing effects in risky decision making. Specifically,
does time pressure strengthen or weaken framing effects? On one hand, research
has suggested that framing effects evolve through the deliberation process,
growing larger with time. On the other hand, dual-process theory attributes
framing effects to an intuitive, emotional system that responds automatically to
stimuli. In our experiments, participants made decisions about gambles framed in
terms of either gains or losses, and time pressure was manipulated across blocks.
Results showed increased framing effects under time pressure in both hypothetical
and incentivized choices, which supports the dual-process hypothesis that these
effects arise from a fast, intuitive system.
PMID- 28406377
TI - In a World of Big Data, Small Effects Can Still Matter: A Reply to Boyce, Daly,
Hounkpatin, and Wood (2017).
PMID- 28406378
TI - Corrigendum: What Predicts Children's Fixed and Growth Intelligence Mind-Sets?
Not Their Parents' Views of Intelligence but Their Parents' Views of Failure.
PMID- 28406379
TI - The Neural Basis of Independence Versus Interdependence Orientations: A Voxel
Based Morphometric Analysis of Brain Volume.
AB - Sociocultural research has established independence and interdependence as two
fundamental ways of thinking about oneself and the social world. Recent
neuroscience studies further demonstrate that these orientations modulate brain
activity in various self- and socially related tasks. In the current study, we
explored whether the traits of independence and interdependence are reflected in
anatomical variations in brain structure. We carried out structural brain imaging
on a large sample of healthy participants ( n = 265) who also completed self
report questionnaires of cultural orientations. Voxel-based morphometry analysis
demonstrated that a relative focus of independence (vs. interdependence) was
associated with increased gray-matter volume in a number of self-related regions,
including ventromedial prefrontal cortex, right dorsolateral prefrontal cortex,
and right rostrolateral prefrontal cortex. These results provide novel insights
into the biological basis of sociocultural orientations.
PMID- 28406380
TI - Inferring Perspective Versus Getting Perspective: Underestimating the Value of
Being in Another Person's Shoes.
AB - People use at least two strategies to solve the challenge of understanding
another person's mind: inferring that person's perspective by reading his or her
behavior (theorization) and getting that person's perspective by experiencing his
or her situation (simulation). The five experiments reported here demonstrate a
strong tendency for people to underestimate the value of simulation. Predictors
estimated a stranger's emotional reactions toward 50 pictures. They could either
infer the stranger's perspective by reading his or her facial expressions or
simulate the stranger's perspective by watching the pictures he or she viewed.
Predictors were substantially more accurate when they got perspective through
simulation, but overestimated the accuracy they had achieved by inferring
perspective. Predictors' miscalibrated confidence stemmed from overestimating the
information revealed through facial expressions and underestimating the
similarity in people's reactions to a given situation. People seem to
underappreciate a useful strategy for understanding the minds of others, even
after they gain firsthand experience with both strategies.
PMID- 28406381
TI - If It's Difficult to Pronounce, It Might Not Be Risky: The Effect of Fluency on
Judgment of Risk Does Not Generalize to New Stimuli.
AB - Processing fluency is used as a basis for various types of judgment. For example,
previous research has shown that people judge food additives with names that are
more difficult to pronounce (i.e., that are disfluent) to be more harmful. We
explored the possibility that the association between disfluency and perceived
harmfulness might be in the opposite direction for some categories of stimuli.
Although we found some support for this hypothesis, an improved analysis and
further studies indicated that the effect was strongly dependent on the stimuli
used. We then used stimulus sampling and showed that the original association
between fluency and perceived safety was not replicable with the newly
constructed stimuli. We found the association between fluency and perceived
safety using the newly constructed stimuli in a final study, but only when
pronounceability was confounded with word length. The results cast doubt on
generalizability of the association between pronounceability and perceived safety
and underscore the importance of treating stimulus as a random factor.
PMID- 28406382
TI - Reading What the Mind Thinks From How the Eye Sees.
AB - Human eyes convey a remarkable variety of complex social and emotional
information. However, it is unknown which physical eye features convey mental
states and how that came about. In the current experiments, we tested the
hypothesis that the receiver's perception of mental states is grounded in
expressive eye appearance that serves an optical function for the sender.
Specifically, opposing features of eye widening versus eye narrowing that
regulate sensitivity versus discrimination not only conveyed their associated
basic emotions (e.g., fear vs. disgust, respectively) but also conveyed opposing
clusters of complex mental states that communicate sensitivity versus
discrimination (e.g., awe vs. suspicion). This sensitivity-discrimination
dimension accounted for the majority of variance in perceived mental states
(61.7%). Further, these eye features remained diagnostic of these complex mental
states even in the context of competing information from the lower face. These
results demonstrate that how humans read complex mental states may be derived
from a basic optical principle of how people see.
PMID- 28406383
TI - Estimating Parallel Processing in a Language Task Using Single-Trial
Intracerebral Electroencephalography.
AB - We provide a quantitative assessment of the parallel-processing hypothesis
included in various language-processing models. First, we highlight the
importance of reasoning about cognitive processing at the level of single trials
rather than using averages. Then, we report the results of an experiment in which
the hypothesis was tested at an unprecedented level of granularity with
intracerebral data recorded during a picture-naming task. We extracted patterns
of significant high-gamma activity from multiple patients and combined them into
a single analysis framework that identified consistent patterns. Average signals
from different brain regions, presumably indexing distinct cognitive processes,
revealed a large degree of concurrent activity. In comparison, at the level of
single trials, the temporal overlap of detected significant activity was
unexpectedly low, with the exception of activity in sensory cortices. Our novel
methodology reveals some limits on the degree to which word production involves
parallel processing.
PMID- 28406384
TI - Lack of Increase in Sexual Drive and Function After Dopaminergic Stimulation in
Women.
AB - Human and animal data indicate that the dopaminergic system plays a crucial role
in sexual drive and function. Using a double-blind, placebo-controlled crossover
design, this prototype study investigated the effect of the D2 dopamine agonist
cabergoline on sexual parameters in 13 healthy women. Cardiovascular and genital
parameters were monitored continuously. Sexual drive and function were measured
using self-report sexual experience scales. In contrast to previous theories and
assumptions, we found that cabergoline did not alter objective and subjective
sexual parameters in healthy women. This finding suggests that there may be sex
differences in the influence of the dopaminergic system on human sexual
functioning.
PMID- 28406385
TI - Retrospective chart review of hospitalizations and costs associated with the
treatment of adults with Philadelphia-negative B-cell relapsed or refractory
acute lymphoblastic leukemia in Belgium.
AB - OBJECTIVES: To quantify hospitalizations and costs among adults with Philadelphia
negative relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL)
who received current salvage chemotherapies in Belgium. METHODS: A retrospective
chart review identified patients aged >=18 years and hospitalized between 2005
and 2015 for Ph-negative R/R B-cell ALL. Data were collected from the index date
(first diagnosis of R/R ALL) until death or loss to follow-up. The salvage
chemotherapy period was defined as the first chemotherapy hospitalization after
the index date to the earliest of death, loss to follow-up, last chemotherapy
dose plus 30 days, or initiation of hematological stem cell transplantation
(HSCT). The primary endpoint was the percent of time in the hospital during the
salvage chemotherapy period. Hospitalization costs were reported from the public
health care payer perspective. RESULTS: Nineteen patients were included, with
median age of 37 years. The average proportion of time patients spent in the
hospital during the salvage chemotherapy period was 50.5%. From the index date to
death, patients received a mean of 1.8 lines of chemotherapy, most commonly hyper
CVAD (31%). There was a mean of 5.5 inpatient hospitalizations and 40.1
outpatient visits with 40.8 outpatient lab tests. Mean costs per patient were
?79,973 for hospitalization (excluding HSCT), ?26,337 for HSCT, ?21,007 for
chemotherapy drugs, and ?6,341 for outpatient management, resulting in a total
cost from the payer's perspective of ?133,965 per patient. CONCLUSION: Adults
with Ph-negative R/R ALL spend half the time receiving salvage chemotherapy in
the hospital. Their treatment is associated with large reimbursement costs in
Belgium.
PMID- 28406386
TI - Practice patterns of occupational medicine physicians in Canada.
AB - The objectives of this survey were to identify the practice patterns of Canadian
physicians working in the field of occupational medicine and to determine whether
the type of certification influences the nature of the work they perform in the
field. An Internet-based survey was conducted in September 2015 of members of the
Occupational and Environmental Medicine Association of Canada. Eighty-six
Canadian-based occupational medicine physicians completed the survey (response
rate 36%). These physicians performed a wide variety of tasks (12 +/- 6), with
few spending most of their time doing a single task. The most frequently
performed tasks were fitness-to-work (78%) and return-to-work evaluations (78%).
Specialty-trained physicians were more likely to be involved in teaching and
research and less likely to be involved in a variety of ability-to-work
evaluations.
PMID- 28406387
TI - Development and Validation of the Transgender Inclusive Behavior Scale (TIBS).
AB - Transgender-inclusive behaviors are actions and communication supporting
transgender individuals. Examples include using language not reinforcing the
gender binary, asking for and using correct pronouns, creation of spaces that
welcome members of the transgender community, and acknowledging cisgender (non
transgender) privilege. A survey was developed measuring this behavior in
individuals to examine the impact of transgender-inclusive behavior and the
potential effect of interventions on promoting inclusive behavior. Data were
collected utilizing an online survey (N = 1,051). The sample was split in half to
run two sets of cases in a principal components analysis. Analysis of the full
sample showed Cronbach's alpha to be .93 (n = 918). Findings suggest that the
Transgender Inclusive Behavior Scale (TIBS) may be a useful instrument for
identifying behaviors related to being inclusive of transgender individuals,
groups, and communities. It may also be used to measure behavior change before
and after transgender-specific educational and behavioral interventions.
PMID- 28406388
TI - Outcomes Following Traumatic Grain Elevator Injuries.
AB - OBJECTIVES: The absence of a comprehensive database of grain elevator-associated
injuries hinders accurate evaluation of injury prevalence and may lead to
discordant information about injury frequencies. The main purpose of this study
was to identify the most common mechanisms of injury related to grain elevator
events. Comparisons of hospital outcomes between patients who sustained traumatic
injuries associated with grain elevators at Occupational Safety and Health
Administration (OSHA)-regulated industrial sites versus those on OSHA-exempt
farming operations were also made. METHODS: A retrospective review was conducted
of all patients' presenting with grain elevator-related injuries at a level-1
trauma center between January 1, 2003, and December 31, 2013. Data collected
included demographics, mechanism of injury, injury severity, hospitalization
details, and discharge disposition. Data were summarized, and comparisons were
made between the groups. RESULTS: All patients (N = 18) in the study were male,
with a mean age of 37 years. Falls and being caught in equipment each accounted
for 27.8% of injuries. Among the 18 patients, there were a total of 37 injuries.
The majority of injuries were either lower extremity (29.7%) or chest injuries
(21.6%). The average hospital length of stay was 4 +/- 4.5 days, and one patient
required mechanical ventilation. There were no reported deaths. CONCLUSION: The
literature reports entrapments as the leading cause of grain elevator-related
injuries; however, this study found that falls and being caught in equipment were
the most common mechanisms of injury. This suggests that a greater emphasis
should be placed on fall prevention and equipment safety.
PMID- 28406389
TI - The informational turn in food politics: The US FDA's nutrition label as
information infrastructure.
AB - This article traces the history of the US FDA regulation of nutrition labeling,
identifying an 'informational turn' in the evolving politics of food, diet and
health in America. Before nutrition labeling was introduced, regulators actively
sought to segregate food markets from drug markets by largely prohibiting health
information on food labels, believing such information would 'confuse' the
ordinary food consumer. Nutrition labeling's emergence, first in the 1970s as
consumer empowerment and then later in the 1990s as a solution to information
overload, reflected the belief that it was better to manage markets indirectly
through consumer information than directly through command-and-control regulatory
architecture. By studying product labels as 'information infrastructure', rather
than a 'knowledge fix', the article shows how labels are situated at the center
of a legally constructed terrain of inter-textual references, both educational
and promotional, that reflects a mix of market pragmatism and evolving legal
thought about mass versus niche markets. A change to the label reaches out across
a wide informational environment representing food and has direct material
consequences for how food is produced, distributed, and consumed. One legacy of
this informational turn has been an increasing focus by policymakers, industry,
and arguably consumers on the politics of information in place of the politics of
the food itself.
PMID- 28406390
TI - Search engine imaginary: Visions and values in the co-production of search
technology and Europe.
AB - This article discusses the co-production of search technology and a European
identity in the context of the EU data protection reform. The negotiations of the
EU data protection legislation ran from 2012 until 2015 and resulted in a unified
data protection legislation directly binding for all European member states. I
employ a discourse analysis to examine EU policy documents and Austrian media
materials related to the reform process. Using the concept 'sociotechnical
imaginary', I show how a European imaginary of search engines is forming in the
EU policy domain, how a European identity is constructed in the envisioned
politics of control, and how national specificities contribute to the making and
unmaking of a European identity. I discuss the roles that national
technopolitical identities play in shaping both search technology and Europe,
taking as an example Austria, a small country with a long history in data
protection and a tradition of restrained technology politics.
PMID- 28406391
TI - A material political economy: Automated Trading Desk and price prediction in high
frequency trading.
AB - This article contains the first detailed historical study of one of the new high
frequency trading (HFT) firms that have transformed many of the world's financial
markets. The study, of Automated Trading Desk (ATD), one of the earliest and most
important such firms, focuses on how ATD's algorithms predicted share price
changes. The article argues that political-economic struggles are integral to the
existence of some of the 'pockets' of predictable structure in the otherwise
random movements of prices, to the availability of the data that allow algorithms
to identify these pockets, and to the capacity of algorithms to use these
predictions to trade profitably. The article also examines the role of HFT
algorithms such as ATD's in the epochal, fiercely contested shift in US share
trading from 'fixed-role' markets towards 'all-to-all' markets.
PMID- 28406392
TI - The right to a human in the loop: Political constructions of computer automation
and personhood.
AB - Contributing to recent scholarship on the governance of algorithms, this article
explores the role of dignity in data protection law addressing automated decision
making. Delving into the historical roots of contemporary disputes between
information societies, notably European Union and Council of Europe countries and
the United States, reveals that the regulation of algorithms has a rich,
culturally entrenched, politically relevant backstory. The article compares the
making of law concerning data protection and privacy, focusing on the role
automation has played in the two regimes. By situating diverse policy treatments
within the cultural contexts from which they emerged, the article uncovers and
examines two different legal constructions of automated data processing, one that
has furnished a right to a human in the loop that is intended to protect the
dignity of the data subject and the other that promotes and fosters full
automation to establish and celebrate the fairness and objectivity of computers.
The existence of a subtle right across European countries and its absence in the
US will no doubt continue to be relevant to international technology policy as
smart technologies are introduced in more and more areas of society.
PMID- 28406393
TI - Is Medical Environment Detrimental to Memory? A Test of A White Coat Effect on
Older People's Memory Performance.
AB - OBJECTIVES: Test if older people's memory assessment may be impacted by a medical
environment and if memory self-efficacy (MSE) will moderate this effect. METHODS:
We evaluated memory performance and MSE in 27 older adults in two different
settings: a (control) university research environment, or a (proxy-medical)
neuropsychological examination environment. RESULTS: The results showed a MSE *
environment interaction effect on story-recall performance, with older people
with low MSE performing less well in the proxy-medical situation than in the
control situation and with elders with high MSE performing better in the proxy
medical situation than in the control situation. The same marginally significant
effect for the word-span task was also found. CONCLUSIONS: Testing in a medical
environment undermines the memory performance of older people with low MSE and
boosts performance of older people with high MSE. Clinical Implications We
encourage neuropsychologists to pay attention to psychosocial determinants of
older people's performance when assessing their memory abilities.
PMID- 28406394
TI - A randomised controlled trial to compare the safety, effectiveness and cost
effectiveness of doxycycline (200 mg/day) with that of oral prednisolone (0.5
mg/kg/day) for initial treatment of bullous pemphigoid: the Bullous Pemphigoid
Steroids and Tetracyclines (BLISTER) trial.
AB - BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disorder
with increased morbidity and mortality in the elderly. OBJECTIVES: To evaluate
the effectiveness, safety and cost-effectiveness of a strategy of initiating BP
treatment with oral doxycycline or oral prednisolone. We hypothesised that
starting treatment with doxycycline gives acceptable short-term blister control
while conferring long-term safety advantages over starting treatment with oral
prednisolone. DESIGN: Pragmatic multicentre two-armed parallel-group randomised
controlled trial with an economic evaluation. SETTING: A total of 54 dermatology
secondary care centres in the UK and seven in Germany. PARTICIPANTS: Adults with
BP [three or more blisters at two sites and positive direct and/or indirect
immunofluorescence (immunoglobulin G and/or complement component 3
immunofluorescence at the dermal-epidermal junction)] and able to give informed
consent. INTERVENTIONS: Participants were allocated using online randomisation to
initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to
30 g/week of potent topical corticosteroids was permitted for weeks 1-3. After 6
weeks, clinicians could switch treatments or alter the prednisolone dose as per
normal practice. MAIN OUTCOME MEASURES: Primary outcomes: (1) the proportion of
participants with three or fewer blisters at 6 weeks (investigator blinded) and
(2) the proportion with severe, life-threatening and fatal treatment-related
events at 52 weeks. A regression model was used in the analysis adjusting for
baseline disease severity, age and Karnofsky score, with missing data imputed.
Secondary outcomes included the effectiveness of blister control after 6 weeks,
relapses, related adverse events and quality of life. The economic evaluation
involved bivariate regression of costs and quality-adjusted life-years (QALYs)
from a NHS perspective. RESULTS: In total, 132 patients were randomised to
doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and
baseline severity was as follows: mild 31.6% (three to nine blisters), moderate
39.1% (10-30 blisters) and severe 29.3% (> 30 blisters). For those starting on
doxycycline, 83 out of 112 (74.1%) had three or fewer blisters at 6 weeks,
whereas for those starting on prednisolone 92 out of 101 (91.1%) had three or
fewer blisters at 6 weeks, an adjusted difference of 18.6% in favour of
prednisolone [90% confidence interval (CI) 11.1% to 26.1%], using a modified
intention-to-treat (mITT) analysis. Per-protocol analysis showed similar results:
74.4% compared with 92.3%, an adjusted difference of 18.7% (90% CI 9.8% to
27.6%). The rate of related severe, life-threatening and fatal events at 52 weeks
was 18.2% for those started on doxycycline and 36.6% for those started on
prednisolone (mITT analysis), an adjusted difference of 19.0% (95% CI 7.9% to
30.1%; p = 0.001) in favour of doxycycline. Secondary outcomes showed consistent
findings. There was no significant difference in costs or QALYs per patient at 1
year between doxycycline-initiated therapy and prednisolone-initiated therapy
(incremental cost of doxycycline-initiated therapy L959, 95% CI -L24 to L1941;
incremental QALYs of doxycycline-initiated therapy -0.024, 95% CI -0.088 to
0.041). Using a willingness-to-pay criterion of < L20,000 per QALY gained, the
net monetary benefit associated with doxycycline-initiated therapy was negative
but imprecise (-L1432, 95% CI -L3094 to L230). CONCLUSIONS: A strategy of
starting BP patients on doxycycline is non-inferior to standard treatment with
oral prednisolone for short-term blister control and considerably safer in the
long term. The limitations of the trial were the wide non-inferiority margin, the
moderate dropout rate and that serious adverse event collection was unblinded.
Future work might include inducing remission with topical or oral corticosteroids
and then randomising to doxycycline or prednisolone for maintenance. TRIAL
REGISTRATION: Current Controlled Trials ISRCTN13704604. FUNDING: This project was
funded by the National Institute for Health Research (NIHR) Health Technology
Assessment programme and will be published in full in Health Technology
Assessment; Vol. 21, No. 10. See the NIHR Journals Library website for further
project information.
PMID- 28406395
TI - Pushing the envelope.
AB - Primates have co-opted a viral gene to produce an envelope protein that prevents
infection by the HERV-T virus and likely contributed to the extinction of this
virus.
PMID- 28406396
TI - SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation.
AB - The Ras family of GTPases are important in cell signaling and frequently mutated
in human tumors. Understanding their regulation is thus important for studying
biology and human diseases. Here, we report that a novel posttranslational
mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the
Ras family. SIRT6, a sirtuin with established tumor suppressor function,
regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts
(MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty
acylation promotes the plasma membrane localization of R-Ras2 and its interaction
with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased
cell proliferation. Our study establishes lysine fatty acylation as a previously
unknown mechanism that regulates the Ras family of GTPases and provides an
important mechanism by which SIRT6 functions as a tumor suppressor.
PMID- 28406397
TI - Evolutionary changes in transcription factor coding sequence quantitatively alter
sensory organ development and function.
AB - Animals are characterized by a set of highly conserved developmental regulators.
Changes in the cis-regulatory elements of these regulators are thought to
constitute the major driver of morphological evolution. However, the role of
coding sequence evolution remains unresolved. To address this question, we used
the Atonal family of proneural transcription factors as a model. Drosophila
atonal coding sequence was endogenously replaced with that of atonal homologues
(ATHs) at key phylogenetic positions, non-ATH proneural genes, and the closest
homologue to ancestral proneural genes. ATHs and the ancestral-like coding
sequences rescued sensory organ fate in atonal mutants, in contrast to non-ATHs.
Surprisingly, different ATH factors displayed different levels of proneural
activity as reflected by the number and functionality of sense organs. This
proneural potency gradient correlated directly with ATH protein stability,
including in response to Notch signaling, independently of mRNA levels or codon
usage. This establishes a distinct and ancient function for ATHs and demonstrates
that coding sequence evolution can underlie quantitative variation in sensory
development and function.
PMID- 28406398
TI - Lissencephaly-1 is a context-dependent regulator of the human dynein complex.
AB - The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule
organisation and cargo transport. These functions are spatially regulated by
association of dynein and its accessory complex dynactin with dynamic microtubule
plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein
1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus
end-directed human dynein complexes with these sites. LIS1 promotes dynactin
dependent tracking of dynein on both growing and shrinking plus ends. LIS1 also
increases the frequency and velocity of processive dynein movements that are
activated by complex formation with dynactin and a cargo adaptor. This
stimulatory effect of LIS1 contrasts sharply with its documented ability to
inhibit the activity of isolated dyneins. Collectively, our findings shed light
on how mammalian dynein complexes associate with dynamic microtubules and help
clarify how LIS1 promotes the plus-end localisation and cargo transport functions
of dynein in vivo.
PMID- 28406401
TI - Le microbiote intestinal : un organe a part entiere.
PMID- 28406399
TI - Automated deep-phenotyping of the vertebrate brain.
AB - Here, we describe an automated platform suitable for large-scale deep-phenotyping
of zebrafish mutant lines, which uses optical projection tomography to rapidly
image brain-specific gene expression patterns in 3D at cellular resolution.
Registration algorithms and correlation analysis are then used to compare 3D
expression patterns, to automatically detect all statistically significant
alterations in mutants, and to map them onto a brain atlas. Automated deep
phenotyping of a mutation in the master transcriptional regulator fezf2 not only
detects all known phenotypes but also uncovers important novel neural deficits
that were overlooked in previous studies. In the telencephalon, we show for the
first time that fezf2 mutant zebrafish have significant patterning deficits,
particularly in glutamatergic populations. Our findings reveal unexpected
parallels between fezf2 function in zebrafish and mice, where mutations cause
deficits in glutamatergic neurons of the telencephalon-derived neocortex.
PMID- 28406402
TI - Behcet disease in Western Algeria.
AB - The aim of the current study was to describe the epidemiological and clinical
features of Behcet disease in western Algeria. This observational retrospective
study examined records for patients with Behcet disease seen in our department
from 1990 to 2015. Of the 61 patients included in the study, 80.3% were men, for
a sex ratio of 4.08. The mean age at onset was 27.2+/-7 years, and the mean
interval between the onset of symptoms and diagnosis was 4.8+/-6.3 years.
Dermatologic manifestations were the most common finding. Oral ulcers were seen
in all patients, genital ulcers in 60%, pseudofolliculitis in 56.4%, and erythema
nodosum in 13.5%. A pathergy test was positive in 20% of the patients. The
frequencies of the remaining manifestations were as follows: joint involvement
50%, ocular involvement 71.2%, vascular complications 29.6%, neurological
involvement 19%, and gastrointestinal complications 7.5%. Besides dermatological
manifestations, ocular and vascular complications were the most common features
observed in our patients.
PMID- 28406400
TI - The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader
involved in the response to DNA damage.
AB - Site-specific histone ubiquitylation plays a central role in orchestrating the
response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events
controlled by the ubiquitin ligase RNF168, which promotes the accumulation of
repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site.
RNF168 also promotes its own accumulation, and that of its paralog RNF169, but
how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY
solution NMR spectroscopy and molecular dynamics simulations, we present an
atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome,
and validate it by electron cryomicroscopy. We establish that RNF169 binds to
ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin
binding helix and a pair of arginine-rich motifs that interact with the
nucleosome acidic patch. This three-pronged interaction mechanism is distinct
from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the
diversity in site-specific recognition of ubiquitylated nucleosomes.
PMID- 28406403
TI - Rhabdomyolysis during envenomation by Physalia sp envenomation in New Caldonia.
AB - We report the first case of rhabdomyolysis following envenomation by a Physalia
sp in New Caledonia. Systemic envenomation by this marine hydrozoan is well
known, including myalgia as a commonly reported clinical feature. Nonetheless, a
related increase in muscle enzymes, featuring rhabdomyolysis, has not previously
been described. In this case report, we describe a patient with rhabdomyolysis
and acute renal failure. Rhabdomyolysis should be checked in case of systemic
physalia envenomation.
PMID- 28406404
TI - Risk of daytime transmission of malaria in the French Guiana rain forest.
AB - Between 2008 and 2014, there were 1070 malaria cases reported in French Guiana
among members of the armed forces. Most of the malaria outbreaks investigated
were multifactorial and followed missions conducted at illegal gold mining sites.
For example, a malaria outbreak occurred in September 2013, three weeks after the
deployment of 15 soldiers at Dagobert, which is such a site. The attack rate was
53%, with seven Plasmodium vivax infections and one coinfection with both
Plasmodium vivax and Plasmodium falciparum. Two months later, an entomological
investigation in the field caught 321 anopheles by the human landing catch
method. Among them, 282 were Anopheles darlingi. One specimen was PCR-positive
for P. vivax, for an infection rate of 0.4% (1/282). In 15.7% of these cases, the
An. darlingi was caught during the day. The existence of daytime biting activity
by An. darlingi in the Guianese forest might play a key role in malaria outbreaks
among military personnel. This finding requires that the Army Health Service
adapt its recommendations concerning malaria prevention in French Guiana.
PMID- 28406405
TI - Risk factors of cholera transmission in rural areas in Haiti.
AB - Cholera, present in Haiti since October 2010, persisted in early 2014 in several
places, each with its own particular epidemiological characteristics. The
scarcity of fresh water probably contributed to the spread of the disease in some
rural areas. Population gatherings in places without an access to either safe
water or sanitation infrastructure were another factor. Outreach activities of
hygiene promotion and improving access to chlorinated water had positive results.
The disappearance of cholera in areas where effective preventive actions were
conducted supports the conclusion that its transmission is predominantly
interhuman, without the sustainable installation of the pathogenic Vibrio in the
Haitian environment. These actions must be modulated according to the various
areas.
PMID- 28406406
TI - Cervical cancer in sub-Saharan Africa: an emerging and preventable disease
associated with oncogenic human papillomavirus.
AB - Highly oncogenic human papillomavirus (HPV) infections are responsible for 7.7 %
of cancers in developing countries, mainly cervical cancer. The incidence of this
emerging cancer is steadily increasing in sub-Saharan Africa, with more than
75,000 new cases and close to 50,000 deaths a year, a toll further increased by
HIV infection. According to the World Health Organization, cervical cancer will
kill more than 443,000 women per year worldwide by 2030, nearly 90 % of them in
sub-Saharan Africa. This increase in cervical cancer incidence in Africa is now
counteracting the progress made by African women in reducing maternal mortality
and increasing longevity. Nevertheless, cervical cancer is a potentially
preventable noncommunicable disease that can be averted or halted by primary
(vaccination), secondary (early diagnosis of situations at risk), and tertiary
(early diagnosis of proven cases of cervical neoplasia) prevention. The close
links between HIV and HPV justify linking cervical cancer prevention, screening,
and management programs with AIDS programs as part of the "90-90-90" initiative
of the UNAIDS, both nationally and regionally. Innovative strategies based on
effective, rapid, inexpensive, and mobile screening tools, including at best
molecular biology as well as vaccination and awareness programs, should be
rapidly implemented and evaluated in sub-Saharan Africa.
PMID- 28406407
TI - Prevalence de la toxocarose.
PMID- 28406408
TI - Leishmaniose cutanee et pentamidine.
PMID- 28406409
TI - Dyspepsie et Helicobacter pylori.
PMID- 28406410
TI - Regression de l'oxyurose.
PMID- 28406412
TI - Arthrite apres morsure de mouton.
PMID- 28406411
TI - Hydatidose endemique.
PMID- 28406413
TI - Lung nodule in French Guiana in a immunocompetent patient.
AB - We report the case of an immunocompetent French soldier stationed in French
Guiana, who developed symptomatic pulmonary histoplasmosis.
PMID- 28406414
TI - Review of poxvirus: emergence of monkeypox.
AB - This article reviews the different types of poxvirus infections. Smallpox,
although eradicated, must continue to be monitored because of the potential risk
of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox
viruses are considered to be emergent today ; their high risk of dissemination is
due to the increase in international transport as well as trends for new animals
as pets and the loss of vaccinal protection against smallpox. Molluscum
contagiosum (molluscipoxvirus) causes mild infections, is particularly frequent
in children ; in adults it is a marker of the risk of sexually transmitted
infections and can, in cases with profuse lesions, reveal AIDS.
PMID- 28406415
TI - Epidemiological profile of cutaneous leishmaniasis in Morocco, 2004-2013.
AB - The main objective of our study is to provide a comprehensive overview of the
situation of cutaneous leishmaniasis in Morocco. We therefore conducted a
retrospective descriptive study covering the decade 2004-2013. Data were
collected from the Moroccan Ministry of Health's annual reports about the
national program against leishmaniasis. These data show a regression in the cases
due to Leishmania major and the persistence of L. tropica transmission. Mapping
cutaneous leishmaniasis cases reported between 2004 and 2013 showed geographical
changes ; the number of cases due to L. tropica were concentrated in the regions
of Marrakech-Tensift-Elhaouz, Souss Massa-Draa Tadla-Azila, and Taza-Al Hoceima
Taounate. Cutaneous disease due to L. major was most common in the Souss-Massa
Draa region. Continuous monitoring of the epidemiological situation is important
to assess the actions taken to reduce its incidence.
PMID- 28406416
TI - Can we continue to support vertical programs for priority diseases without paying
attention to the health policies in limited-resource countries?
PMID- 28406417
TI - A rare complication of viper envenomation: cardiac failure. A case report.
AB - Viper envenomation is common in North Africa. Cardiac complications are not
common features of snakebites, the clinical picture of which is usually dominated
by toxin-associated neurological, hematological, and vascular damage. There are
rare reports of acute myocardial infarction and/or ischemia caused by snakebites,
while myocarditis after envenomation has not yet been reported, to our knowledge.
We report the case of a 43-year-old woman admitted to our intensive care unit
after viper envenomation complicated by acute heart failure with acute pulmonary
edema, in a state of cardiogenic shock, accompanied by multi-organ failure,
intravascular disseminated coagulation, and neurological damage. Some of the
mechanisms that may be involved in this heart failure are discussed, including
the possibility of acute myocarditis.
PMID- 28406418
TI - Collective poisoning from sea turtle consumption in Mahajanga Madagascar, May
2014.
AB - Poisoning from eating sea turtles, medically known as chelonitoxism, is seen
especially in coastal areas. It remains a public health problem in Madagascar,
despite a ban on hunting these animals. The objective of this study was to
describe its epidemiological and clinical aspects and outcome to improve
knowledge and prevention of this type of poisoning. Chelonitoxism occurred in May
2014, affecting the population in Antsanitia, a fishing village in northwest
Mahajanga, Madagascar. All patients came first to the CSB I basic health center
in Antsanitia and were subsequently hospitalized at the Mahajanga CHU Pzaga, 51
in the adult emergency department and 25 in the pediatrics department. These 76
patients ranged in age from 3 months to 79 years. The predominant clinical signs
were gastrointestinal and neurological disorders. ENT-oral signs characterized
the poisoning. Ingestion of the turtle fat caused intermediate and severe disease
forms in adults. Breastfeeding was a prognostic factor in children. Signs of
severity appeared within 72 hours in adults. After intensive resuscitation, the
signs of poisoning disappeared after 12 days. The severe form predominated in
children; death was either early or delayed to the second to sixth day after
consumption. It is essential to develop awareness of this danger among the entire
coastal population of Madagascar to prevent this kind of poisoning.
PMID- 28406419
TI - Brachial circumference as an alternative to body mass index for the detection of
in-hospital undernutrition in a referal hospital, Cameroon.
AB - The prevalence of undernutrition in hospitals in Africa is estimated at about 57
%. Simple anthropometric methods are available to detect it, including
measurement of the brachial circumference (BC) and the body mass index (BMI). The
aim of this study was to identify a threshold value that might make it possible
to diagnose undernutrition in hospitals. It was a cross sectional study carried
out at Douala General Hospital - Cameroon over a five months period. The
measurements studied were: BMI, BC and percentage of weight loss. The Pearson
test was used to compare the quantitative variables. The Receiving Operating
Characteristic curve enabled us to determine a threshold value of the BC
according to BMI. The study included 333 patients, with a mean age of 45 +/- 16
years (range : 18-86). BMI and BC were strongly correlated; BC =11.69 +
0.68(BMI), with r2 = 0.65 (P < 0.01)). The threshold value of BC retained to
detect undernutrition was 27 cm. The prevalence of undernutrition at the Douala
General Hospital varies according to the anthropometric parameter used. At a BC
threshold of 27 cm, the prevalence of undenutrition in our population was 24,3%.
PMID- 28406420
TI - Epidemiological, clinical, and therapeutic features of typhoid intestinal
perforation in a rural environment of Burkina Faso.
AB - The aim of this study was to describe the epidemiological, clinical, and
therapeutic features of ileal perforation due to typhoid fever at the regional
hospital of Tenkodogo (Burkina Faso). This cross-sectional study examined the
records over a 5-year period of all patients treated for typhoid ileal
perforation. Ileal perforation was diagnosed intraoperatively, and its typhoid
origin determined according to the following criteria : background signs of
typhoid fever, location of the perforation on the antimesenteric edge of the
terminal ileum, and a positive Widal-Felix serology. The study included 216
patients. Their mean age was 13.8 years, and 63.4% were male. The average time to
consultation was 11 days. Clinical signs were mainly abdominal pain, vomiting,
and abdominal tenderness. Anemia was observed in 135 patients (62.5%). All
patients underwent laparotomy. Three procedures for treating surgical perforation
were used : excision and suture of the perforation in 86 patients (39.8%), ileal
resection with anastomosis in 98 (45.4%), and ileostomy with subsequent recovery
in 32 (14.8%). The average length of hospital stay was 16.1 days. Postoperative
complications occurred in 156 patients (72.2%). Thirty-seven patients died, for a
mortality rate of 17.1 %. Ileal perforations due to typhoid fever are the main
cause of peritonitis in rural areas of Burkina Faso. Patients are relatively
young, and most are anemic at admission. Morbidity and mortality are significant.
PMID- 28406421
TI - Advantages and disadvantages of using the PRISMA7 to determine the elderly
subjects for whom the SMAF is useful for assessing functional status in Bobo
Dioulasso (Burkina Faso).
AB - One of the difficulties faced by African actors working with the elderly is the
lack of appropriate tools for the identification and/or diagnosis of functional
disabilities among older people in this limited-resource (material, human, and
financial) setting. This study sought to assess the advantages and disadvantages
of the combined use of two tools, PRISMA7 (for identifying older individuals at
risk of functional disabilities and loss of autonomy) and SMAF (to evaluate the
functional status of the elderly) in Bobo-Dioulasso (Burkina Faso). PRISMA7 and
SMAF were administered to a representative sample of elderly people who lived at
home. Data analysis was performed with Stata. The results show that the
combination of PRISMA7 and SMAF made it possible to avoid unncessary
administration of the SMAF to all subjects, reducing the number of questionnaires
to photocopy by 48 % and the working time by 45 %. The prevalence of moderate to
severe functional disabilities was 32 % according to the SMAF alone and 25 % when
PRISMA7 was administered first and determined whether the SMAF would be used. The
7 % rate of loss to follow-up shows a need for monitoring or help, generally in
instrumental activities. In a limited-resource setting, this combination is a
good strategy for identifying and evaluating functional disabilities in the
elderly. This strategy allows the development of work plans tailored to
individual functional needs.
PMID- 28406422
TI - Nutritional status of people living with HIV/AIDS in the Ratoma community medical
center (Republic of Guinea).
AB - The nutritional status of people living with HIV/AIDS (PLHIV) has a direct impact
on their health. The aim of this study was to describe the nutritional status of
PLWHA receiving care at the Ratoma community medical center in Conakry, Guinea.
This quantitative cross-sectional study assessed the nutritional status of 184
people PLHIV receiving antiretroviral treatment. The sample comprised 184 PLHIV
selected by a systematic random sampling from the complete list of PLHIV. The
data were collected by individual questionnaires. Two groups were defined
according to their nutritional status, based on their body mass index (BMI): a
malnourished group (BMI < 18,5kg/m2) and a well-nourished group (BMI >=
18,5kg/m2). CD4 lymphocyte counts were also collected. Of the 184 PLVIH, 19.6%
were malnourished (95%CI: 14.1-25.0). The mean BMI was 22.2 +/- 4.3 kg/m2). The
mean CD4 count differed significantly between the groups (328.7+/-237.7 CD4
cells/mm3 for the malnourished group and 432.9+/-256.9 for the well-nourished, p
<0.017). Malnutrition was significantly associated with a low CD4 count. To
improve survival and quality of life among PLHIV, this high frequency of
malnutrition calls for sustained attention to the prevention and early detection
and treatment of malnutrition in the early stages of HIV.
PMID- 28406423
TI - Epidemiological aspects of genital ulcers at the STI center of the National
Institute of Public Hygiene (Abidjan, Cote d'Ivoire) 2008 to 2010.
AB - Genital ulcers are among the seven syndromes of sexually transmitted infections
(STIs) identified in Cote d'Ivoire. Ulcerative STIs present a public health
problem because of their frequency and their role in the spread of HIV. Our
objective was to investigate the epidemiological characteristics of genital
ulcers observed in the STI center of the National Institute of Public Hygiene in
Abidjan. This cross-sectional, descriptive and analytical study examined cases
seen at the center in 2008 through 2010. We retrospectively reviewed all files of
clients aged 10 and older who sought care for the first time at the STI center
and received a clinical diagnosis, confirmed by the laboratory, of a STI.
Overall, we selected 2488 records. Men accounted for 52.30%. The patients'
average age was 32 years. The prevalence of genital ulcers was 3.90%. Genital
herpes was the diagnosed mentioned most often by doctors (71.43%), followed by
scabies (19.39%) and chancroids (9.18%). Male sex and multiple sexual partners
appeared to be risk factors for genital ulcers at this center. Genital ulcers are
infrequent. Public awareness campaigns to encourage changes in behavior must
continue and intensify. In particular, they must stress control of genital herpes
by well-known prevention methods: regular and correct condom use and fewer sexual
partners.
PMID- 28406424
TI - Rapid tests and transfusion safety in Niamey, Niger.
AB - To evaluate the virological safety of blood components provided by the Niamey
blood transfusion center after undergoing rapid tests. Samples found negative
with rapid tests (n = 222) were screened by the Abbott Prism assay. Positive
samples were confirmed by appropriate methods. Of 222 samples, nine (4.1%) were
reactive for all markers. After confirmation, seven samples were positive (i.e.,
3.2% false-negative results) : five (2.3%) for the surface antigen of hepatitis B
(HBsAg) and two (0.9%) for the antibody directed against the hepatitis C virus
(HCV-Ab). No false negative results were observed for HIV-Ab (antibody directed
against the Human Immunodeficiency Virus). The performance of the rapid tests
used in Niamey to screen for transfusion-transmissible infections is not
satisfactory, especially for hepatitis B and C. The use of more sensitive tests
should be considered to minimize the risk of contaminating patients receiving
blood components.
PMID- 28406425
TI - Shubnikov-de Haas measurements on a high mobility monolayer graphene flake
sandwiched between boron nitride sheets.
AB - A flake of monolayer graphene was sandwiched between boron nitride sheets.
Temperature dependent Shubnikov-de Haas measurements were performed to access how
this technique influences the electronic properties of the graphene sample. The
maximum mobility found in this configuration was approximately 105 cm2 Vs -1.
From the phase of the oscillations a Berry phase beta of 1/2 was obtained
indicating the presence of Dirac fermions. We obtained Fermi velocities around
[Formula: see text] m s-1 which imply hopping energies close to 2.5 eV.
Furthermore, the carrier lifetime is typically higher than that found in graphene
supported by SiO2, reaching values higher than 700 fs.
PMID- 28406426
TI - Autonomous Car Parking System through a Cooperative Vehicular Positioning
Network.
AB - The increasing development of the automotive industry towards a fully autonomous
car has motivated the design of new value-added services in Vehicular Sensor
Networks (VSNs). Within the context of VSNs, the autonomous car, with an
increasing number of on-board sensors, is a mobile node that exchanges sensed and
state information within the VSN. Among all the value added services for VSNs,
the design of new intelligent parking management architectures where the
autonomous car will coexist with traditional cars is mandatory in order to profit
from all the opportunities associated with the increasing intelligence of the new
generation of cars. In this work, we design a new smart parking system on top of
a VSN that takes into account the heterogeneity of cars and provides guidance to
the best parking place for the autonomous car based on a collaborative approach
that searches for the common good of all of them measured by the accessibility
rate, which is the ratio of the free parking places accessible for an autonomous
car. Then, we simulate a real parking lot and the results show that the
performance of our system is close to the optimum considering different
communication ranges and penetration rates for the autonomous car.
PMID- 28406427
TI - Ten Important Considerations for Ovarian Cancer Screening.
AB - The unique intricacies of ovarian cancer screening and perspectives of different
screening methods are presented as ten considerations that are examined. Included
in these considerations are: (1) Deciding on the number of individuals to be
screened; (2) Anticipating screening group reductions due to death; (3) Deciding
on the duration and frequency of screening; (4) Deciding on an appropriate follow
up period after screening; (5) Deciding on time to surgery when malignancy is
suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by
whom; (7) Deciding on how to treat the data of enrolled participants; (8)
Deciding on the most appropriate way to assign disease-specific death; (9)
Deciding how to avoid biases caused by enrollments that attract participants with
late-stage disease who are either symptomatic or disposed by factors that are
genetic, environmental or social; and (10) Deciding whether the screening tool or
a screening process is being tested. These considerations are presented in depth
along with illustrations of how they impact the outcomes of ovarian cancer
screening. The considerations presented provide alternative explanations of
effects that have an important bearing on interpreting ovarian screening
outcomes.
PMID- 28406428
TI - Green Care: A Review of the Benefits and Potential of Animal-Assisted Care
Farming Globally and in Rural America.
AB - The term Green Care includes therapeutic, social or educational interventions
involving farming; farm animals; gardening or general contact with nature.
Although Green Care can occur in any setting in which there is interaction with
plants or animals, this review focuses on therapeutic practices occurring on
farms. The efficacy of care farming is discussed and the broad utilization of
care farming and farm care communities in Europe is reviewed. Though evidence
from care farms in the United States is included in this review, the empirical
evidence which could determine its efficacy is lacking. For example, the
empirical evidence supporting or refuting the efficacy of therapeutic horseback
riding in adults is minimal, while there is little non-equine care farming
literature with children. The health care systems in Europe are also much
different than those in the United States. In order for insurance companies to
cover Green Care techniques in the United States, extensive research is
necessary. This paper proposes community-based ways that Green Care methods can
be utilized without insurance in the United States. Though Green Care can
certainly be provided in urban areas, this paper focuses on ways rural areas can
utilize existing farms to benefit the mental and physical health of their
communities.
PMID- 28406429
TI - Release of Doxorubicin by a Folate-Grafted, Chitosan-Coated Magnetic
Nanoparticle.
AB - In clinical tumor therapy, chemotherapeutic routes have caused severe side
effects; current delivery methods are unsatisfactory. Successful design of a
remotely folate (FA)-grafted chitosan (CS)-coated magnetic nanoparticle (MNP)
with low toxicity, has been achieved. A chemotherapeutic drug such as doxorubicin
(DOX), is loaded in the MNP-based matrix (FA-grafted CS-DOX-TPP-MNP), which is
coated by an activated target tumor molecule of FA-grafted CS biopolymer with the
inclusion of tripolyphosphate (TPP) as a linker. The resultant nano-complexes
exhibited random aggregates (~240 nm) and zeta potential (-24.9 mV). In vivo
experiments using athymic BALB/c nude mice with human glioblastoma U87 cells in a
subcutaneous tumor model revealed that magnetic guidance of FA-grafted CS-DOX-TPP
MNP, injected via the tail vein, significantly decreased tumor growth. This
manuscript demonstrates the feasibility of magnetizing control of FA-grafted CS
DOX-TPP-MNP to enhance the localization of drug release.
PMID- 28406430
TI - Palliative Care and the Family Caregiver: Trading Mutual Pretense (Empathy) for a
Sustained Gaze (Compassion).
AB - In this conceptual piece, we survey the progress of palliative care communication
and reflect back on a chapter we wrote a decade ago, which featured the
communication concept of mutual pretense, first described by Glaser and Strauss
(1965). This work will include an update on family caregivers and their role in
cancer caregiving as well as a review of current palliative care communication
curriculum available for providers. And finally, we will spotlight the
conversation and research going forward on the subject of health literacy for all
stakeholders; patients, families, providers, and systems. We feature one family's
story of incurable cancer and end of life to revisit the needs we identified ten
years ago, which are still present. Goals for going forward in chronic and
terminal illness are suggested in a health care context still too void of
palliative care communication resources for providers, patients, and especially
family caregivers.
PMID- 28406431
TI - Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by
DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.
AB - In general, atherosclerosis is considered to be a form of chronic inflammation.
Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not
considered for long-term administration on account of a poor pharmacokinetic
profile and adverse side effects. Nanoparticles in which drugs can be dissolved,
encapsulated, entrapped or chemically attached to the particle surface have
abilities to incorporate dexamethasone and to be used as controlled or targeted
drug delivery system. Long circulatory polymeric nanoparticles present as an
assisting approach for controlled and targeted release of the encapsulated drug
at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound
(US) are widely applied in cancer treatment due to their time applications, low
cost, simplicity, and safety. However, there are few studies on atherosclerosis
treatment using polymeric nanoparticles combined with US. In this study, targeted
dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol
cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the
emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials
(PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG
cRGD NPs was 221.6 +/- 0.9 nm. Morphology of the nanoparticles was spherical and
uniformly dispersed. In addition, the DA released profiles suggested that
ultrasound could promote drug release from the nanocarriers and accelerate the
rate of release. In vitro, the cellular uptake process of fluorescein
isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged
human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid
intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA
PEG-cRGD NPs combined with US reached 91.9% +/- 0.2%, which demonstrated that DA
PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged
HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a
promising drug delivery system to enhance the therapeutic effects of these
chemotherapeutics at the cellular level.
PMID- 28406432
TI - A New Strategy for Silver Deposition on Au Nanoparticles with the Use of
Peroxidase-Mimicking DNAzyme Monitored via a Localized Surface Plasmon Resonance
Technique.
AB - Peroxidase-mimicking DNAzyme was applied as a catalyst of silver deposition on
gold nanoparticles. This DNAzyme is formed when hemin binds to the G-quadruplex
forming DNA sequence. Such a system is able to catalyze a redox reaction with a
one- or two-electron transfer. The process of silver deposition was monitored via
a localized surface plasmon resonance technique (LSPR), which allows one to
record scattering spectrum of a single nanoparticle. Our study showed that
DNAzyme is able to catalyze silver deposition. The AFM experiments proved that
DNAzyme induced the deposition of silver shells of approximately 20 nm thickness
on Au nanoparticles (AuNPs). Such an effect is not observed when hemin is absent
in the system. However, we noticed non-specific binding of hemin to the capture
oligonucleotides on a gold NP probe that also induced some silver deposition,
even though the capture probe was unable to form G-quadruplex. Analysis of SEM
images indicated that the surface morphology of the silver layer deposited by
DNAzyme is different from that obtained for hemin alone. The proposed strategy of
silver layer synthesis on gold nanoparticles catalyzed by DNAzyme is an
innovative approach and can be applied in bioanalysis (LSPR, electrochemistry) as
well as in material sciences.
PMID- 28406433
TI - Diversity of Amyloid Motifs in NLR Signaling in Fungi.
AB - Amyloid folds not only represent the underlying cause of a large class of human
diseases but also display a variety of functional roles both in prokaryote and
eukaryote organisms. Among these roles is a recently-described activity in signal
transduction cascades functioning in host defense and programmed cell death and
involving Nod-like receptors (NLRs). In different fungal species, prion amyloid
folds convey activation signals from a receptor protein to an effector domain by
an amyloid templating and propagation mechanism. The discovery of these amyloid
signaling motifs derives from the study of [Het-s], a fungal prion of the species
Podospora anserina. These signaling pathways are typically composed of two basic
components encoded by adjacent genes, the NLR receptor bearing an amyloid motif
at the N-terminal end and a cell death execution protein with a HeLo pore-forming
domain bearing a C-terminal amyloid motif. Activation of the NLR receptor allows
for amyloid folding of the N-terminal amyloid motifs which then template trans
conformation of the homologous motif in the cell death execution protein. A
variety of such motifs, which differ by their sequence signature, have been
described in fungi. Among them, the PP-motif bears resemblance with the RHIM
amyloid motif involved in the necroptosis pathway in mammals suggesting an
evolutionary conservation of amyloid signaling from fungi to mammals.
PMID- 28406434
TI - Preventive Effects of Heat-Killed Enterococcus faecalis Strain EC-12 on Mouse
Intestinal Tumor Development.
AB - Establishing effective methods for preventing colorectal cancer by so-called
"functional foods" is important because the global burden of colorectal cancer is
increasing. Enterococcus faecalis strain EC-12 (EC-12), which belongs to the
family of lactic acid bacteria, has been shown to exert pleiotropic effects, such
as anti-allergy and anti-infectious effects, on mammalian cells. In the present
study, we aimed to evaluate the preventive effects of heat-killed EC-12 on
intestinal carcinogenesis. We fed 5-week-old male and female Apc mutant Min mice
diets containing 50 or 100 ppm heat-killed EC-12 for 8 weeks. In the 50 ppm
treated group, there was 4.3% decrease in the number of polyps in males vs. 30.9%
in females, and significant reduction was only achieved in the proximal small
intestine of female mice. A similar reduction was observed in the 100 ppm treated
group. Moreover, heat-killed EC-12 tended to reduce the levels of c-Myc and
cyclin D1 mRNA expression in intestinal polyps. Next, we confirmed that heat
killed EC-12 suppressed the transcriptional activity of the T-cell
factor/lymphoid enhancer factor, a transcriptional factor involved in cyclin D1
mRNA expression in intestinal polyps. Our results suggest that heat-killed EC-12
very weakly suppresses intestinal polyp development in Min mice, in part by
attenuating beta-catenin signaling, and this implies that heat-killed EC-12 could
be used as a "functional food".
PMID- 28406436
TI - Modeling Infrared Signal Reflections to Characterize Indoor Multipath
Propagation.
AB - In this paper, we propose a model to characterize Infrared (IR) signal
reflections on any kind of surface material, together with a simplified procedure
to compute the model parameters. The model works within the framework of Local
Positioning Systems (LPS) based on IR signals (IR-LPS) to evaluate the behavior
of transmitted signal Multipaths (MP), which are the main cause of error in IR
LPS, and makes several contributions to mitigation methods. Current methods are
based on physics, optics, geometry and empirical methods, but these do not meet
our requirements because of the need to apply several different restrictions and
employ complex tools. We propose a simplified model based on only two reflection
components, together with a method for determining the model parameters based on
12 empirical measurements that are easily performed in the real environment where
the IR-LPS is being applied. Our experimental results show that the model
provides a comprehensive solution to the real behavior of IR MP, yielding small
errors when comparing real and modeled data (the mean error ranges from 1% to 4%
depending on the environment surface materials). Other state-of-the-art methods
yielded mean errors ranging from 15% to 40% in test measurements.
PMID- 28406435
TI - Associations of Dietary Glucose, Fructose, and Sucrose with beta-Cell Function,
Insulin Sensitivity, and Type 2 Diabetes in the Maastricht Study.
AB - The associations of glucose, fructose, and sucrose intake with type 2 diabetes
mellitus (T2DM) have been inconsistent. Furthermore, there is a lack of studies
focusing on early markers of T2DM that provide insight into the process of T2DM
progression: impaired pancreatic beta-cell function (BCF) and insulin
sensitivity. This study evaluated associations cross-sectionally in a population
based cohort consisting of 2818 individuals (mean +/- SD age 59.7 +/- 8.18, 49.5%
male, n = 120 newly diagnosed T2DM). Glucose, fructose, and sucrose intake were
assessed by a food frequency questionnaire. Glucose metabolism status, insulin
sensitivity, and BCF were measured by a seven-points oral glucose tolerance test.
Linear regression analysis revealed a positive association of glucose intake with
insulin sensitivity in the fully adjusted model (standardized beta (95% CI) 0.07
(0.05, 0.14) SD for >=23 g vs. <10 g of glucose). Fructose and sucrose intake
were not associated with insulin sensitivity after full adjustments. In addition,
no associations of dietary glucose, fructose, and sucrose with BCF were detected.
In conclusion, higher intake of glucose, not fructose and sucrose, was associated
with higher insulin sensitivity, independent of dietary fibre. No convincing
evidence was found for associations of dietary glucose, fructose, and sucrose
with BCF in this middle-aged population.
PMID- 28406437
TI - Low Glycemic Index Prototype Isomaltulose-Update of Clinical Trials.
AB - Low glycemic index diets are supposed to achieve a more beneficial effect on
blood glucose control in people with diabetes mellitus and may also provide
metabolic benefits for the general population. A prototype of a low-glycemic
index carbohydrate is the natural occurring disaccharide isomaltulose that can be
commercially produced from sucrose (beet sugar) to industrial scale. It is
currently used in various food and drink applications as well as special and
clinical nutrition feeds and formula diet as a food ingredient and alternative
sugar. Here we provide an overview on clinical trials with isomaltulose including
an analysis of its effects on glycemia and fat oxidation as compared to high
glycemic index sugars and carbohydrates. In addition, we discuss recent reports
on beneficial effects in weight-loss maintenance and pregnancy.
PMID- 28406438
TI - U.S. Trends of ED Visits for Pediatric Traumatic Brain Injuries: Implications for
Clinical Trials.
AB - Our goal in this paper was to use the 2006-2013 Nationwide Emergency Department
Sample (NEDS) database to describe trends of annual patient number, patient
demographics and hospital characteristics of pediatric traumatic brain injuries
(TBI) treated in U.S. emergency departments (EDs); and to use the same database
to estimate the available sample sizes for various clinical trials of pediatric
TBI cases. National estimates of patient demographics and hospital
characteristics were calculated for pediatric TBI. Simulation analyses assessed
the potential number of pediatric TBI cases from randomly selected hospitals for
inclusion in future clinical trials under different scenarios. Between 2006 and
2013, the NEDS database estimated that of the 215,204,932 children who visited
the ED, 6,089,930 (2.83%) had a TBI diagnosis. During the study period in the US
EDs, pediatric TBI patients increased by 34.1%. Simulation analyses suggest that
hospital EDs with annual TBI ED visits >1000, Levels I and II Trauma Centers,
pediatric hospitals, and teaching hospitals will likely provide ample cases for
pediatric TBI studies. However, recruiting severe pediatric TBI cases for
clinical trials from a limited number of hospital EDs will be challenging due to
small sample sizes. Pediatric TBI-related ED visits in the U.S. increased by over
30% from 2006 to 2013. Including unspecified head injury cases with ICD-9-CM code
959.01 would significantly change the national estimates and demographic patterns
of pediatric TBI cases. Future clinical trials of children with TBI should
conduct a careful feasibility assessment to estimate their sample size and study
power in selected study sites.
PMID- 28406440
TI - Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel
Disease: A Meta-Analysis.
AB - BACKGROUND: Inflammatory bowel disease (IBD) patients may be at risk of vitamin
B12 and folate insufficiencies, as these micronutrients are absorbed in the small
intestine, which is affected by IBD. However, a consensus has not been reached on
the association between IBD and serum folate and vitamin B12 concentrations.
METHODS: In this study, a comprehensive search of multiple databases was
performed to identify studies focused on the association between IBD and serum
folate and vitamin B12 concentrations. Studies that compared serum folate and
vitamin B12 concentrations between IBD and control patients were selected for
inclusion in the meta-analysis. RESULTS: The main outcome was the mean difference
in serum folate and vitamin B12 concentrations between IBD and control patients.
Our findings indicated that the average serum folate concentration in IBD
patients was significantly lower than that in control patients, whereas the mean
serum vitamin B12 concentration did not differ between IBD patients and controls.
In addition, the average serum folate concentration in patients with ulcerative
colitis (UC) but not Crohn's disease (CD) was significantly lower than that in
controls. This meta-analysis identified a significant relationship between low
serum folate concentration and IBD. CONCLUSIONS: Our findings suggest IBD may be
linked with folate deficiency, although the results do not indicate causation.
Thus, providing supplements of folate and vitamin B12 to IBD patients may improve
their nutritional status and prevent other diseases.
PMID- 28406439
TI - Protein-Coding Genes' Retrocopies and Their Functions.
AB - Transposable elements, often considered to be not important for survival,
significantly contribute to the evolution of transcriptomes, promoters, and
proteomes. Reverse transcriptase, encoded by some transposable elements, can be
used in trans to produce a DNA copy of any RNA molecule in the cell. The
retrotransposition of protein-coding genes requires the presence of reverse
transcriptase, which could be delivered by either non-long terminal repeat (non
LTR) or LTR transposons. The majority of these copies are in a state of "relaxed"
selection and remain "dormant" because they are lacking regulatory regions;
however, many become functional. In the course of evolution, they may undergo
subfunctionalization, neofunctionalization, or replace their progenitors.
Functional retrocopies (retrogenes) can encode proteins, novel or similar to
those encoded by their progenitors, can be used as alternative exons or create
chimeric transcripts, and can also be involved in transcriptional interference
and participate in the epigenetic regulation of parental gene expression. They
can also act in trans as natural antisense transcripts, microRNA (miRNA) sponges,
or a source of various small RNAs. Moreover, many retrocopies of protein-coding
genes are linked to human diseases, especially various types of cancer.
PMID- 28406441
TI - Beverage Consumption Habits among the European Population: Association with Total
Water and Energy Intakes.
AB - BACKGROUND: Fluid and water intake have received limited attention in
epidemiological studies. The aim of this study was to compare the average daily
consumption of foods and beverages in adults of selective samples of the European
Union (EU) population in order to understand the contribution of these to the
total water intake (TWI), evaluate if the EU adult population consumes adequate
amounts of total water (TW) according to the current guidelines, and to
illustrate the real water intake in Europe. METHODS: Three national European
dietary surveys have been selected: Spain used the Anthropometry, Intake, and
Energy Balance Study (ANIBES) population database, Italy analyzed data from the
Italian National Food Consumption Survey (INRAN-SCAI 2005-06), and French data
came from the NutriNet-Sante database. Mean daily consumption was used to compare
between individuals. TWI was compared with European Food Safety Authority (EFSA)
reference values for adult men and women. RESULTS: On average, in Spain, TWI was
1.7 L (SE 22.9) for men and 1.6 L (SE 19.4) for women; Italy recorded 1.7 L (SE
16.9) for men and 1.7 L (SE 14.1) for women; and France recorded 2.3 L (SE 4.7)
for men and 2.1 L (SE 2.4) for women. With the exception of women in France,
neither men nor women consumed sufficient amounts of water according to EFSA
reference values. CONCLUSIONS: This study highlights the need to formulate
appropriate health and nutrition policies to increase TWI in the EU population.
The future of beverage intake assessment requires the use of new instruments,
techniques, and the application of the new available technologies.
PMID- 28406442
TI - Liposomal Encapsulation for Systemic Delivery of Propranolol via Transdermal
Iontophoresis Improves Bone Microarchitecture in Ovariectomized Rats.
AB - The stimulatory effects of liposomal propranolol (PRP) on proliferation and
differentiation of human osteoblastic cells suggested that the prepared liposomes
encapsulated PRP exerts anabolic effects on bone in vivo. Iontophoresis provides
merits such as sustained release of drugs and circumvention of first pass
metabolism. This study further investigated and evaluated the anti-osteoporotic
effects of liposomal PRP in ovariectomized (OVX) rats via iontophoresis. Rats
subjected to OVX were administered with pure or liposomal PRP via iontophoresis
or subcutaneous injection twice a week for 12 weeks. Changes in the
microarchitecture at the proximal tibia and the fourth lumbar spine were assessed
between pure or liposomal PRP treated and non-treated groups using micro-computed
tomography. Administration of liposomal PRP at low dose (0.05 mg/kg) via
iontophoresis over 2-fold elevated ratio between bone volume and total tissue
volume (BV/TV) in proximal tibia to 9.0% whereas treatment with liposomal PRP at
low and high (0.5 mg/kg) doses via subcutaneous injection resulted in smaller
increases in BV/TV. Significant improvement of BV/TV and bone mineral density
(BMD) was also found in the fourth lumbar spine when low-dose liposomal PRP was
iontophoretically administered. Iontophoretic low-dose liposomal PRP also
elevated trabecular numbers in tibia and trabecular thickness in spine.
Enhancement of bone microarchitecture volumes has highlighted that liposomal
formulation with transdermal iontophoresis is promising for PRP treatment at the
lower dose and with longer duration than its clinical therapeutic range and
duration to exhibit optimal effects against bone loss in vivo.
PMID- 28406443
TI - Smoke-Free Laws and Hazardous Drinking: A Cross-Sectional Study among U.S.
Adults.
AB - Tobacco and alcohol use are strongly associated. This cross-sectional study
examined the relationship of smoke-free law coverage and smoke-free bar law
coverage with hazardous drinking behaviors among a representative sample of U.S.
adult drinkers (n = 17,057). We merged 2009 National Health Interview Survey
data, American Nonsmokers' Rights Foundation U.S. Tobacco Control Laws Database,
and Census Population Estimates. Hazardous drinking outcomes included heavy
drinking (>14 drinks/week for men; >7 drinks/week for women) and binge drinking
(>=5 drinks on one or more days during past year). Chi-square tests compared
hazardous drinking by sociodemographic factors. Multivariable logistic regression
models were used to examine if smoke-free law and bar law coverages were
associated with hazardous drinking, controlling for sociodemographics and smoking
status. Subset analyses were conducted among drinkers who also smoked (n = 4074)
to assess the association between law coverages and hazardous drinking. Among all
drinkers, smoke-free law coverage was not associated with heavy drinking
(adjusted odds ratio (AOR) = 1.22, 95% confidence interval (CI) = 0.99-1.50) or
binge drinking (AOR = 1.09, 95% CI = 0.93-1.26). Smoke-free bar law coverage was
also found to be unrelated to hazardous drinking. Similar results were found
among those drinkers who smoked. Findings suggest that smoke-free laws and bar
laws are not associated with elevated risk for alcohol-related health issues.
PMID- 28406444
TI - Identification of Drought-Responsive MicroRNAs from Roots and Leaves of Alfalfa
by High-Throughput Sequencing.
AB - Alfalfa, an important forage legume, is an ideal crop for sustainable agriculture
and a potential crop for bioenergy resources. Drought, one of the most common
environmental stresses, substantially affects plant growth, development, and
productivity. MicroRNAs (miRNAs) are newly discovered gene expression regulators
that have been linked to several plant stress responses. To elucidate the role of
miRNAs in drought stress regulation of alfalfa, a high-throughput sequencing
approach was used to analyze 12 small RNA libraries comprising of four samples,
each with three biological replicates. From the 12 libraries, we identified 348
known miRNAs belonging to 80 miRNA families, and 281 novel miRNAs, using Mireap
software. Eighteen known miRNAs in roots and 12 known miRNAs in leaves were
screened as drought-responsive miRNAs. With the exception of miR319d and miR157a
which were upregulated under drought stress, the expression pattern of drought
responsive miRNAs was different between roots and leaves in alfalfa. This is the
first study that has identified miR3512, miR3630, miR5213, miR5294, miR5368 and
miR6173 as drought-responsive miRNAs. Target transcripts of drought-responsive
miRNAs were computationally predicted. All 447 target genes for the known miRNAs
were predicted using an online tool. This study provides a significant insight on
understanding drought-responsive mechanisms of alfalfa.
PMID- 28406446
TI - Is There any Alternative to Canonical DNA Barcoding of Multicellular Eukaryotic
Species? A Case for the Tubulin Gene Family.
AB - Modern taxonomy is largely relying on DNA barcoding, a nucleotide sequence-based
approach that provides automated species identification using short orthologous
DNA regions, mainly of organellar origin when applied to multicellular Eukaryotic
species. Target DNA loci have been selected that contain a minimal amount of
nucleotide sequence variation within species while diverging among species. This
strategy is quite effective for the identification of vertebrates and other
animal lineages but poses a problem in plants where different combinations of two
or three loci are constantly used. Even so, species discrimination in such plant
categories as ornamentals and herbals remain problematic as well as the confident
identification of subspecies, ecotypes, and closely related or recently evolved
species. All these limitations may be successfully solved by the application of a
different strategy, based on the use of a multi-locus, ubiquitous, nuclear
marker, that is tubulin. In fact, the tubulin-based polymorphism method can
release specific genomic profiles to any plant species independently from its
taxonomic group. This offers the rare possibility of an effective yet generic
genomic fingerprint. In a more general context, the issue is raised about the
possibility that approaches alternative to systematic DNA sequencing may still
provide useful and simple solutions.
PMID- 28406447
TI - PVDF Sensor Stimulated by Infrared Radiation for Temperature Monitoring in
Microfluidic Devices.
AB - This paper presents a ferroelectric polymer-based temperature sensor designed for
microfluidic devices. The integration of the sensor into a system-on-a-chip
platform facilitates quick monitoring of localized temperature of a biological
fluid, avoiding errors in the evaluation of thermal evolution of the fluid during
analysis. The contact temperature sensor is fabricated by combining a thin
pyroelectric film together with an infrared source, which stimulates the active
element located on the top of the microfluidic channel. An experimental setup was
assembled to validate the analytical model and to characterize the response rate
of the device. The evaluation procedure and the operating range of the
temperature also make this device suitable for applications where the localized
temperature monitoring of biological samples is necessary. Additionally, ease of
integration with standard microfluidic devices makes the proposed sensor an
attractive option for in situ analysis of biological fluids.
PMID- 28406445
TI - Morphofunctional Alterations in Zebrafish (Danio rerio) Gills after Exposure to
Mercury Chloride.
AB - Mercury (Hg) is a global pollutant that may exert its toxic effects on living
organisms and is found in both aquatic and terrestrial ecosystems in three
chemical forms; elemental, organic, and inorganic. The inorganic form (iHg) tends
to predominantly accumulate in aquatic environments. The gill apparatus is a very
dynamic organ that plays a fundamental role in gas exchange, osmoregulation, acid
base regulation, detoxification, and excretion, and the gills are the primary
route of waterborne iHg entrance in fish. In the present work we investigated the
morphofunctional and ultrastructural effects in Danio rerio gills after 96 h
exposure to two low HgCl2 concentrations (7.7 and 38.5 ug/L). Our results clearly
demonstrated that a short-term exposure to low concentrations of mercury chloride
resulted in gill morphology alterations and in the modifications of both Na+/K+
ATPase and metallothioneins (MTs) expression pattern. The main morphological
effects recorded in this work were represented by hyperplasia and ectopia of
chloride cells (CCs), lamellar fusion, increased mucous secretion, alteration of
pavement cells (PVCs), detachment of the secondary epithelium, pillar cell
degeneration, degeneration, and apoptosis. Trough immunohistochemistry and real
time PCR analysis also showed a dose-related modulation of Na+/K+-ATPase and MTs.
PMID- 28406448
TI - Development of a New, High Sensitivity 2000 kg Mechanical Balance.
AB - Mass measurement of more than 500 kg on an electronic mass comparator has no
better repeatability and linearity of measurement for meeting the calibration
requirement of over class F1 weights from pharmacy and power generation plants.
For this purpose, a new 2000 kg mechanical balance was developed by the National
Institute of Metrology (NIM). The advantages of measurement of more than 500 kg
on a new 2000 kg mechanical balance are introduced in the paper. In order to
obtain high measurement uncertainty, four vertical forces of two sides of beam
are measured and used as reference for adjustment of the beam position. Laser
displacement sensors in the indication system are more effective for decreasing
reading errors caused by human vision. To improve the repeatability and
sensitivity of the equipment, a synchronous lifting control is designed for
synchronously lifting the beam ends along the vertical direction. A counterweight
selection system is developed to get any combination of weights in a limited
space. The sensitivity of the new mechanical balance for 2000 kg is more than 1.7
parts in 10-4 rad/g. The extended uncertainties for the mechanical balance of 500
kg, 1000 kg and 2000 kg are 0.47 g, 1.8 g and 3.5 g respectively.
PMID- 28406449
TI - Improved Object Detection Using a Robotic Sensing Antenna with Vibration Damping
Control.
AB - Some insects or mammals use antennae or whiskers to detect by the sense of touch
obstacles or recognize objects in environments in which other senses like vision
cannot work. Artificial flexible antennae can be used in robotics to mimic this
sense of touch in these recognition tasks. We have designed and built a two
degree of freedom (2DOF) flexible antenna sensor device to perform robot
navigation tasks. This device is composed of a flexible beam, two servomotors
that drive the beam and a load cell sensor that detects the contact of the beam
with an object. It is found that the efficiency of such a device strongly depends
on the speed and accuracy achieved by the antenna positioning system. These
issues are severely impaired by the vibrations that appear in the antenna during
its movement. However, these antennae are usually moved without taking care of
these undesired vibrations. This article proposes a new closed-loop control
schema that cancels vibrations and improves the free movements of the antenna.
Moreover, algorithms to estimate the 3D beam position and the instant and point
of contact with an object are proposed. Experiments are reported that illustrate
the efficiency of these proposed algorithms and the improvements achieved in
object detection tasks using a control system that cancels beam vibrations.
PMID- 28406450
TI - What Does It "Mean"? A Review of Interpreting and Calculating Different Types of
Means and Standard Deviations.
AB - Typically, investigations are conducted with the goal of generating inferences
about a population (humans or animal). Since it is not feasible to evaluate the
entire population, the study is conducted using a randomly selected subset of
that population. With the goal of using the results generated from that sample to
provide inferences about the true population, it is important to consider the
properties of the population distribution and how well they are represented by
the sample (the subset of values). Consistent with that study objective, it is
necessary to identify and use the most appropriate set of summary statistics to
describe the study results. Inherent in that choice is the need to identify the
specific question being asked and the assumptions associated with the data
analysis. The estimate of a "mean" value is an example of a summary statistic
that is sometimes reported without adequate consideration as to its implications
or the underlying assumptions associated with the data being evaluated. When
ignoring these critical considerations, the method of calculating the variance
may be inconsistent with the type of mean being reported. Furthermore, there can
be confusion about why a single set of values may be represented by summary
statistics that differ across published reports. In an effort to remedy some of
this confusion, this manuscript describes the basis for selecting among various
ways of representing the mean of a sample, their corresponding methods of
calculation, and the appropriate methods for estimating their standard
deviations.
PMID- 28406451
TI - An On-Site, Ultra-Sensitive, Quantitative Sensing Method for the Determination of
Total Aflatoxin in Peanut and Rice Based on Quantum Dot Nanobeads Strip.
AB - An on-site, ultra-sensitive, and quantitative sensing method was developed based
on quantum dot nanobeads (QDNBs) and a test strip for the determination of total
aflatoxins (AFTs) in rice and peanuts. The monoclonal antibody against AFT
(mAbAFT) was homemade and labeled with QDNB. After the pre-coating of the AFT
antigen on the test line (T line), the competitive immunoreactions were conducted
between AFT and AFT antigen on the T line with QDNBs-mAbAFT. Under optimal
conditions, this approach allowed a rapid response towards AFT with a
considerable sensitivity of 1.4 pg/mL and 2.9 pg/mL in rice and peanut matrices,
respectively. The put-in and put-out durations were within 10 min. The recoveries
for AFT in rice and peanut sample matrices were recorded from 86.25% to 118.0%,
with relative deviations (RSD) below 12%. The assay was further validated via the
comparison between this QDNB strip and the conventional HPLC method using spiked
samples. Thus, the design provided a potential alternative for on-site, ultra
sensitive, and quantitative sensing of AFT that could also be expanded to other
chemical contaminants for food safety.
PMID- 28406452
TI - Suppression of Hepatic Epithelial-to-Mesenchymal Transition by Melittin via
Blocking of TGFbeta/Smad and MAPK-JNK Signaling Pathways.
AB - Transforming growth factor (TGF)-beta1 plays a crucial role in the epithelial-to
mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC),
which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a
major component of bee venom and is effective in rheumatoid arthritis, pain
relief, cancer cell proliferation, fibrosis and immune modulating activity. In
this study, we found that MEL inhibits hepatic EMT in vitro and in vivo,
regulating the TGFbeta/Smad and TGFbeta/nonSmad signaling pathways. MEL
significantly inhibited TGF-beta1-induced expression of EMT markers (E-cadherin
reduction and vimentin induction) in vitro. These results were confirmed in CCl4
induced liver in vivo. Treatment with MEL almost completely blocked the
phosphorylation of Smad2/3, translocation of Smad4 and phosphorylation of JNK in
vitro and in vivo. Taken together, these results suggest that MEL suppresses EMT
by inhibiting the TGFbeta/Smad and TGFbeta/nonSmad-c-Jun N-terminal kinase
(JNK)/Mitogen-activated protein kinase (MAPK) signaling pathways. These results
indicated that MEL possesses potent anti-fibrotic and anti-EMT properties, which
may be responsible for its effects on liver diseases.
PMID- 28406454
TI - Loss of the Phenolic Hydroxyl Group and Aromaticity from the Side Chain of Anti
Proliferative 10-Methyl-aplog-1, a Simplified Analog of Aplysiatoxin, Enhances
Its Tumor-Promoting and Proinflammatory Activities.
AB - Aplysiatoxin (ATX) is a protein kinase C (PKC) activator with potent tumor
promoting activity. In contrast, 10-methyl-aplog-1 (1), a simplified analog of
ATX, was anti-proliferative towards several cancer cell lines without significant
tumor-promoting and proinflammatory activities. To determine the effects of the
phenolic group on the biological activities of 1, we synthesized new derivatives
(2, 3) that lack the phenolic hydroxyl group and/or the aromatic ring. Compound
2, like 1, showed potent anti-proliferative activity against several cancer cell
lines, but little with respect to tumor-promoting and proinflammatory activities.
In contrast, 3 exhibited weaker growth inhibitory activity, and promoted
inflammation and tumorigenesis. The binding affinity of 3 for PKCdelta, which is
involved in growth inhibition and apoptosis, was several times lower than those
of 1 and 2, possibly due to the absence of the hydrogen bond and CH/pi
interaction between its side chain and either Met-239 or Pro-241 in the PKCdelta
C1B domain. These results suggest that both the aromatic ring and phenolic
hydroxyl group can suppress the proinflammatory and tumor-promoting activities of
1 and, therefore, at least the aromatic ring in the side chain of 1 is
indispensable for developing anti-cancer leads with potent anti-proliferative
activity and limited side effects. In accordance with the binding affinity, the
concentration of 3 necessary to induce PKCdelta-GFP translocation to the plasma
membrane and perinuclear regions in HEK293 cells was higher than that of 1 and 2.
However, the translocation profiles for PKCdelta-GFP due to induction by 1-3 were
similar.
PMID- 28406453
TI - Sequence Polymorphism and Intrinsic Structural Disorder as Related to
Pathobiological Performance of the Helicobacter pylori CagA Oncoprotein.
AB - CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally
associated with the development of gastrointestinal diseases such as chronic
gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric
epithelial cells via bacterial type IV secretion, CagA interacts with a number of
host proteins through the intrinsically disordered C-terminal tail, which
contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA)
motif and the CagA multimerization (CM) motif. The EPIYA motif, upon
phosphorylation by host kinases, binds and deregulates Src homology 2 domain
containing protein tyrosine phosphatase 2 (SHP2), a bona fide oncoprotein,
inducing pro-oncogenic mitogenic signaling and abnormal cell morphology. Through
the CM motif, CagA inhibits the kinase activity of polarity regulator
partitioning-defective 1b (PAR1b), causing junctional and polarity defects while
inducing actin cytoskeletal rearrangements. The magnitude of the pathobiological
action of individual CagA has been linked to the tandem repeat polymorphisms of
these two binding motifs, yet the molecular mechanisms by which they affect
disease outcome remain unclear. Recent studies using quantitative techniques have
provided new insights into how the sequence polymorphisms in the structurally
disordered C-terminal region determine the degree of pro-oncogenic action of CagA
in the gastric epithelium.
PMID- 28406455
TI - Subcellular Localization of Arabidopsis Pathogenesis-Related 1 (PR1) Protein.
AB - The Arabidopsisthaliana pathogenesis-related 1 (PR1) is an important defense
protein, so far it has only been detected in extracellular space and its
subcellular sorting and transport remain unexplained. Using a green fluorescent
protein (GFP) tagged full length, as well as a C-terminus truncated version of
PR1, we observed that when expressed ectopically in Nicotiana benthamiana leaves,
PR1 co-localizes only partially with Golgi markers, and much more prominently
with the late endosome (LE)/multivesicular body (MVB) FYVE marker. The C
truncated version PR1DeltaC predominantly localized to the endoplasmic reticulum
(ER). The same localizations were found for stable Arabidopsis transformants with
expression of PR1 and PR1DeltaC driven by the native promoter. We conclude that
the A. thaliana PR1 (AtPR1) undergoes an unconventional secretion pathway,
starting from the C-terminus-dependent sorting from the ER, and utilizing further
transportation via phosphatidyl-inositol-3-phosphate (PI(3)P) positive LE/MVB
like vesicles. The homology model of the PR1 structure shows that the cluster of
positively charged amino acid residues (arginines 60, 67, 137, and lysine 135)
could indeed interact with negatively charged phospholipids of cellular
membranes. It remains to be resolved whether Golgi and LE/MVB localization
reflects an alternative sorting or trafficking succession, and what the role of
lipid interactions in it will be.
PMID- 28406456
TI - Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and
Inhibits Epithelial-Mesenchymal Transition.
AB - Cordycepin (3'-deoxyadenosine) is a natural compound abundantly found in
Cordyceps sinesis in natural and fermented sources. In this study, we examined
the effects of cordycepin in a human oral squamous cell carcinoma (OSCC)
xenograft model. Cordycepin was administered in a regular, low-dose and prolonged
schedule metronomic therapy. Two doses of cordycepin (25 mg/kg, 50 mg/kg) were
administrated five days a week for eight consecutive weeks. The tumor volumes
were reduced and survival time was significantly prolonged from 30.3 +/- 0.9 days
(control group) to 56 days (50 mg/kg group, the day of tumor-bearing mice were
sacrificed for welfare consideration). The weights of mice did not change and
liver, renal, and hematologic functions were not compromised. Cordycepin
inhibited the OSCC cell viability in vitro (IC50 122.4-125.2 MUM). Furthermore,
morphological characteristics of apoptosis, increased caspase-3 activity and G2/M
cell cycle arrest were observed. In wound healing assay, cordycepin restrained
the OSCC cell migration. Cordycepin upregulated E-cadherin and downregulated N
cadherin protein expression, implying inhibition of epithelial-mesenchymal
transition (EMT). The immunohistochemical staining of xenograft tumor with E
cadherin and vimentin validated in vitro results. In conclusion, metronomic
cordycepin therapy showed effective tumor control, prolonged survival and low
toxicities. Cytotoxicity against cancer cells with apoptotic features and EMT
inhibition were observed.
PMID- 28406457
TI - New Cytotoxic Secondary Metabolites from Marine Bryozoan Cryptosula pallasiana.
AB - A new sterol, (23R)-methoxycholest-5,24-dien-3beta-ol (1), two new ceramides,
(2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and
(2S,3R,2'R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2'-triol (7),
together with three known sterols (2-4), a lactone (5) and two ceramides (8,9),
were isolated from the marine bryozoan Cryptosula pallasiana, collected at Huang
Island of China. The structures of the new compounds were elucidated by extensive
spectroscopic analyses, chemical methods and quantum electronic circular
dichroism (ECD) calculations. Among the isolated compounds, sterol 1 possessed a
rare side chain with a methoxy group at C-23, and a double bond between C-24 and
C-25. Ceramides 6 and 7 possessed 14 carbons in their long-chain fatty acid base
(FAB), which were different from the normal ceramides with 16 carbons in the FAB.
Moreover, compounds 5 and 8 were isolated for the first time from marine
bryozoans. Compounds 1-9 were evaluated for their cytotoxicity against human
tumor cell lines HL-60, Hep-G2 and SGC-7901. The results showed that lactone 5
appears to have strong cytotoxicity against the test tumor cell lines, with IC50
values from 4.12 MUM to 7.32 MUM, and sterol 1 displayed moderate cytotoxicity
with IC50 values between 12.34 MUM and 18.37 MUM, while ceramides 6-9 showed weak
cytotoxicity with IC50 ranging from 21.13 MUM to 58.15 MUM.
PMID- 28406458
TI - Behavior of Human Osteoblast Cells Cultured on Titanium Discs in Relation to
Surface Roughness and Presence of Melatonin.
AB - The aim of this work was to observe the behavior of osteoblast cells cultured in
vitro on titanium discs in relation to disc surface roughness and the addition of
melatonin to the culture medium. MG63 osteoblast cells were cultivated on 120
Grade 5 Ti divided into three groups: Group E, treated with dual acid etch; Group
EP, treated with dual acid etch and calcium phosphate; and Group M, machined.
Surface roughness was examined under a laser scanning confocal microscope (CLSM)
and scanning electron microscopy (SEM). The proliferation and morphology of cells
were determined under fluorescence microscopy and SEM. Messenger ribonucleic acid
(mRNA) of different genes related to osteoblastic differentiation was quantified
by means of real-time quantitative polymerase chain reaction (RT-PCR) assay. The
greatest surface roughness was found in Group EP (Ra 0.354 um), followed by Group
E (Ra 0.266 um), and Group M (Ra 0.131 um), with statistically significant
differences between the groups (p < 0.001). In the presence of melatonin a trend
to a higher cell proliferation was observed in all groups although significant
differences were only found in Group M (p = 0.0079). Among the genes studied, a
significant increase in phosphate-regulating neutral endopeptidase, X-linked
(PHEX) expression was observed in cells cultured on EP discs. The addition of
melatonin increased osteoblast cell proliferation and differentiation, and may
favor the osseointegration of dental implants.
PMID- 28406459
TI - homeSound: Real-Time Audio Event Detection Based on High Performance Computing
for Behaviour and Surveillance Remote Monitoring.
AB - The consistent growth in human life expectancy during the recent years has driven
governments and private organizations to increase the efforts in caring for the
eldest segment of the population. These institutions have built hospitals and
retirement homes that have been rapidly overfilled, making their associated
maintenance and operating costs prohibitive. The latest advances in technology
and communications envisage new ways to monitor those people with special needs
at their own home, increasing their quality of life in a cost-affordable way. The
purpose of this paper is to present an Ambient Assisted Living (AAL) platform
able to analyze, identify, and detect specific acoustic events happening in daily
life environments, which enables the medic staff to remotely track the status of
every patient in real-time. Additionally, this tele-care proposal is validated
through a proof-of-concept experiment that takes benefit of the capabilities of
the NVIDIA Graphical Processing Unit running on a Jetson TK1 board to locally
detect acoustic events. Conducted experiments demonstrate the feasibility of this
approach by reaching an overall accuracy of 82% when identifying a set of 14
indoor environment events related to the domestic surveillance and patients'
behaviour monitoring field. Obtained results encourage practitioners to keep
working in this direction, and enable health care providers to remotely track the
status of their patients in real-time with non-invasive methods.
PMID- 28406461
TI - N-(2,2-Dimethyl-1-(quinolin-2-yl)propylidene) arylaminonickel Complexes and Their
Ethylene Oligomerization.
AB - A series of N-(2,2-dimethyl-1-(quinolin-2-yl)propylidene) arylamines was
sophisticatedly synthesized and reacted with nickel(II) bromine for the formation
of the corresponding nickel complexes. All the organic compounds were
characterized by IR, NMR spectra and elemental analysis, while all the nickel
complexes were characterized by IR spectra and elemental analysis. On activation
with ethylaluminium sesquichloride (EASC) and modified methylaluminoxane (MMAO),
all nickel precatalysts exhibited good activities toward ethylene
oligomerization, indicating the positive efficiency of gem-dimethyl
substitutents; in which major hexenes were obtained with MMAO. The catalytic
parameters were verified, and the steric and electronic influences of
substituents with ligands were observed, with a slight change of activities under
different ethylene pressures.
PMID- 28406460
TI - Assessment of the Antimicrobial Activity and the Entomocidal Potential of
Bacillus thuringiensis Isolates from Algeria.
AB - This work represents the first initiative to analyze the distribution of B.
thuringiensis in Algeria and to evaluate the biological potential of the
isolates. A total of 157 isolates were recovered, with at least one isolate in
94.4% of the samples. The highest Bt index was found in samples from rhizospheric
soil (0.48) and from the Mediterranean area (0.44). Most isolates showed
antifungal activity (98.5%), in contrast to the few that had antibacterial
activity (29.9%). A high genetic diversity was made evident by the finding of
many different crystal shapes and various combinations of shapes within a single
isolate (in 58.4% of the isolates). Also, over 50% of the isolates harbored cry1,
cry2, or cry9 genes, and 69.3% contained a vip3 gene. A good correlation between
the presence of chitinase genes and antifungal activity was observed. More than
half of the isolates with a broad spectrum of antifungal activity harbored both
endochitinase and exochitinase genes. Interestingly, 15 isolates contained the
two chitinase genes and all of the above cry family genes, with some of them
harboring a vip3 gene as well. The combination of this large number of genes
coding for entomopathogenic proteins suggests a putative wide range of
entomotoxic activity.
PMID- 28406462
TI - Effectiveness of a Culturally-Tailored Smoking Cessation Intervention for Arab
American Men.
AB - To date, no smoking cessation programs are available for Arab American (ARA) men,
who are a vulnerable population with high rates of smoking. Thus, the primary aim
of this one group pre-test/post-test study was to assess the effectiveness of
Sehatack-a culturally and linguistically tailored smoking cessation program for
ARA men. The study sample was 79 ARA men with a mean age of 43 years who smoked
between 5 and 40 cigarettes (mean = 19.75, SD = 9.1) per day (98.7%). All of the
participants reported more interest in smoking cessation post-intervention and
many of the participants in the baseline (38.5%) and post-intervention phases
(47.7%) wanted to quit smoking "very much". For daily smokers who completed the
smoking cessation program, the median number of cigarettes smoked daily was
significantly lower than those in the post-intervention phase (Z = -6.915, p <
0.001). Results of this preliminary study indicate that: (a) Sehatack may be a
promising way for ARA men to quit smoking, and (b) culturally relevant smoking
cessation counselors can be trained to recruit and retain ARA smokers in an
intensive group smoking cessation program. Strengths of this study were community
engagement and rapport between three faith organizations and the University of
Florida College of Nursing. However, a larger trial is needed to address study
limitations and to confirm benefits in this population.
PMID- 28406463
TI - Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure
followed by Retro Diels-Alder Protocol.
AB - From 2-aminonorbornene hydroxamic acids, a simple and efficient method for the
preparation of pyrrolo[1,2-a]pyrimidine enantiomers is reported. The synthesis is
based on domino ring-closure followed by microwave-induced retro Diels-Alder
(RDA) protocols, where the chirality of the desired products is transferred from
norbornene derivatives. The stereochemistry of the synthesized compounds was
proven by X-ray crystallography. The absolute configuration of the product is
determined by the configuration of the starting amino hydroxamic acid.
PMID- 28406465
TI - The Use of a Pressure-Indicating Film to Determine the Effect of Liner Type on
the Measured Teat Load Caused by a Collapsing Liner.
AB - During milking the teat cup liner is the interface between the teat of a dairy
cow and the milking system, so it should be very well adapted to the teat.
Therefore, the aim of the present study was to determine the effect of liner type
on the directly measuring teat load caused by a collapsing liner with a pressure
indicating film. The Extreme Low pressure-indicating film was used to detect the
effect of six different liners on teat load. For each liner, six positions in the
teat cup were specified, and six repetitions were performed for each position
with a new piece of film each time. Analysis of variance was performed to detect
differences between the six liners, the positions within a liner, and the
measuring areas. The pressure applied to the teat by a liner depends on the
technical characteristics of the liner, especially the shape of the barrel, and
for all tested liners, a higher teat load was found at the teat end. In
conclusion, with the help of pressure-indicating film, it is possible to
determine the different effects of liner type by directly measuring teat load due
to liner collapse.
PMID- 28406466
TI - Artificial Red Blood Cells as Potential Photosensitizers in Dye Laser Treatment
Against Port-Wine Stains.
AB - We suggest a novel method that uses artificial blood cells (hemoglobin vesicles,
Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port
wine stains (i.e., capillary malformations presenting as red birthmarks) based on
the results of animal experiments. As compared with human red blood cells, Hb-Vs
have the same absorbance of 595 nm wavelength light and produce the same level of
heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in
the plasma phase in blood and tend to flow in the marginal zone of microvessels.
Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye
laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the
intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed
laser photons and produced heat. This extra Hb tended to flow near the
endothelial cells, which were the target of the laser treatment. These attributes
of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser
treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our
proposed treatment may have aspects of photodynamic therapy using porphyrin that
leads to a cytotoxicity effect by active oxygen.
PMID- 28406464
TI - Vitamin D Status, Muscle Strength and Physical Performance Decline in Very Old
Adults: A Prospective Study.
AB - Mixed reports exist about the role of 25-hydroxyvitamin D (25(OH)D) in muscle
ageing and there are few prospective studies involving the very old (aged >= 85)
who are at highest risk of low 25(OH)D, loss of muscle mass and strength, and
physical performance decline. In the Newcastle 85+ Study (n = 845), we aimed to
determine the association between 25(OH)D season-specific quartiles (hereafter
SQ1-SQ4), grip strength (GS) and physical performance decline (Timed Up-and-Go
Test, TUG) over 5 years using mixed models. In the time-only models with linear
and quadratic slopes, SQ1 and SQ4 of 25(OH)D were associated with weaker GS
initially in men (SQ1: beta (SE) = -2.56 (0.96); SQ4: -2.16 (1.06)) and women
(SQ1: -1.10 (0.52); SQ4: -1.28 (0.50)) (all p <= 0.04). In the fully adjusted
models, only men in SQ1 had a significant annual decline in GS of 1.41 kg which
accelerated over time (-0.40 (0.1)), (both p <= 0.003) compared with those in
combined middle quartiles. Only women in SQ1 and SQ4 of 25(OH)D had worse TUG
times initially, but the rate of TUG decline was not affected. Low baseline
25(OH)D may contribute to muscle strength decline in the very old and
particularly in men.
PMID- 28406467
TI - Lead Exposure Assessment among Pregnant Women, Newborns, and Children: Case Study
from Karachi, Pakistan.
AB - Lead (Pb) in petrol has been banned in developed countries. Despite the control
of Pb in petrol since 2001, high levels were reported in the blood of pregnant
women and children in Pakistan. However, the identification of sources of Pb has
been elusive due to its pervasiveness. In this study, we assessed the lead intake
of pregnant women and one- to three-year-old children from food, water, house
dust, respirable dust, and soil. In addition, we completed the fingerprinting of
the Pb isotopic ratios (LIR) of petrol and secondary sources (food, house-dust,
respirable dust, soil, surma (eye cosmetics)) of exposure within the blood of
pregnant women, newborns, and children. Eight families, with high (~50 MUg/dL),
medium (~20 MUg/dL), and low blood levels (~10 MUg/dL), were selected from 60
families. The main sources of exposure to lead for children were food and house
dust, and those for pregnant women were soil, respirable dust, and food. LIR was
determined by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS)
with a two sigma uncertainty of +/-0.03%. The LIR of mothers and newborns was
similar. In contrast, surma, and to a larger extent petrol, exhibited a
negligible contribution to both the child's and mother's blood Pb. Household wet
mopping could be effective in reducing Pb exposure. This intake assessment could
be replicated for other developing countries to identify sources of lead and the
burden of lead exposure in the population.
PMID- 28406468
TI - Foulant Analysis of Three RO Membranes Used in Treating Simulated Brackish Water
of the Iraqi Marshes.
AB - In this work, three different types of Reverse Osmosis (RO) (Thin-Film Composite
(SE), Cellulose Acetate (CE), and Polyamide (AD)) were used to perform foulant
analysis (autopsy) study on the deposited materials from three different
simulated brackish surface feed waters. The brackish surface water qualities
represented the water quality in Iraqi marshes. The main foulants from the
simulated feed waters were characterized by using Scanning Electron Microscope
(SEM) images and Energy-Dispersive X-ray Spectroscopy (EDXS) spectra. The effect
of feed water temperatures (37 degrees C and 11 degrees C) on the formation of
the fouled material deposited on the membrane surface was examined in this study.
Also, pretreatment by a 0.1 micron microfiltration (MF) membrane of the simulated
feed water in advance of the RO membrane on the precipitated material on the
membrane surface was investigated. Finally, Fourier Transform Infrared
Spectroscopy (FTIR) analysis was used to identify the functional groups of the
organic matter deposited on the RO membrane surfaces. The SEM images and EDSX
spectra suggested that the fouled material was mainly organic matter, and the
major crystal deposited on the RO membrane was calcium carbonate (CaCO3). The
FTIR spectra of the fouled RO membranes suggested that the constituents of the
fouled material included aliphatic and aromatic compounds.
PMID- 28406469
TI - Easy-to-Fabricate and High-Sensitivity LSPR Type Specific Protein Detection
Sensor Using AAO Nano-Pore Size Control.
AB - In this study, we developed a pore size/pore area-controlled optical biosensor
based anodic aluminum oxide (AAO) nanostructure. As the pore size of AAO
increases, the unit cell of AAO increases, which also increases the non-pore area
to which the antibody binds. The increase in the number of antibodies immobilized
on the surface of the AAO enables effective detection of trace amounts of
antigen, because increased antigen-antibody bonding results in a larger surface
refractive index change. High sensitivity was thus achieved through amplification
of the interference wave of two vertically-incident reflected waves through the
localized surface plasmon resonance phenomenon. The sensitivity of the fabricated
sensor was evaluated by measuring the change in wavelength with the change in the
refractive index of the device surface, and sensitivity was increased with
increasing pore-size and non-pore area. The sensitivity of the fabricated sensor
was improved and up to 11.8 ag/mL serum amyloid A1 antigen was detected. In
addition, the selectivity of the fabricated sensor was confirmed through a
reaction with a heterogeneous substance, C-reactive protein antigen. By using
hard anodization during fabrication of the AAO, the fabrication time of the
device was reduced and the AAO chip was fabricated quickly and easily.
PMID- 28406470
TI - Spatio-Temporal Pattern and Risk Factor Analysis of Hand, Foot and Mouth Disease
Associated with Under-Five Morbidity in the Beijing-Tianjin-Hebei Region of
China.
PMID- 28406471
TI - Real-Time (Vision-Based) Road Sign Recognition Using an Artificial Neural
Network.
AB - Road sign recognition is a driver support function that can be used to notify and
warn the driver by showing the restrictions that may be effective on the current
stretch of road. Examples for such regulations are 'traffic light ahead' or
'pedestrian crossing' indications. The present investigation targets the
recognition of Malaysian road and traffic signs in real-time. Real-time video is
taken by a digital camera from a moving vehicle and real world road signs are
then extracted using vision-only information. The system is based on two stages,
one performs the detection and another one is for recognition. In the first
stage, a hybrid color segmentation algorithm has been developed and tested. In
the second stage, an introduced robust custom feature extraction method is used
for the first time in a road sign recognition approach. Finally, a multilayer
artificial neural network (ANN) has been created to recognize and interpret
various road signs. It is robust because it has been tested on both standard and
non-standard road signs with significant recognition accuracy. This proposed
system achieved an average of 99.90% accuracy with 99.90% of sensitivity, 99.90%
of specificity, 99.90% of f-measure, and 0.001 of false positive rate (FPR) with
0.3 s computational time. This low FPR can increase the system stability and
dependability in real-time applications.
PMID- 28406472
TI - Lunch Salad Bars in New Orleans' Middle and High Schools: Student Intake of Fruit
and Vegetables.
AB - The school lunch salad bar (SB) is a recommended food environmental strategy to
increase access to, and consumption of fruit and vegetables (F/V). In a study to
examine use of school lunch SBs, middle and high school students provided data
via the Automated Self-Administered 24-h dietary recall (24HDR) tool for kids
(ASA24-Kids-2012), a web-based data collection platform. Kilocalories were
computed, food groups were assigned and F/V sources were obtained. Students (n =
718) from 12 schools with SBs and nine schools without SBs were approximately 87%
African American, over 64% female and most were 7th and 8th graders. SB school
students had higher median energy consumption at lunch but a higher percent of
non-SB students reported eating fruit at lunch compared to SB students. Most
students reporting eating F/V at lunch obtained F/V from the cafeteria main line;
only 19.6% reported eating F/V exclusively from the SB. In SB schools median
intake of cups F/V was higher among students using the SB (0.92) compared to
those not using the SB (0.53). Results of this study are mixed, but encouraging.
Additional factors, e.g., nutrition education, marketing, and kinds of foods
offered on the SB need to be examined for potential influence on SB use.
PMID- 28406473
TI - Restoring visual function to the blind retina with a potent, safe and long
lasting photoswitch.
AB - Photoswitch compounds such as DENAQ confer light-sensitivity on endogenous
neuronal ion channels, enabling photocontrol of neuronal activity without genetic
manipulation. DENAQ treatment restores both retinal light responses and visual
behaviors in rodent models of Retinitis pigmentosa. However, retinal
photosensitization requires a high dose of DENAQ and disappears within several
days after treatment. Here we report that BENAQ, an improved photoswitch, is 20
fold more potent than DENAQ and persists in restoring visual responses to the
retina for almost 1 month after a single intraocular injection. Studies on mice
and rabbits show that BENAQ is non-toxic at concentrations 10-fold higher than
required to impart light-sensitivity. These favorable properties make BENAQ a
potential drug candidate for vision restoration in patients with degenerative
blinding diseases.
PMID- 28406474
TI - Daily touchscreen use in infants and toddlers is associated with reduced sleep
and delayed sleep onset.
AB - Traditional screen time (e.g. TV and videogaming) has been linked to sleep
problems and poorer developmental outcomes in children. With the advent of
portable touchscreen devices, this association may be extending down in age to
disrupt the sleep of infants and toddlers, an age when sleep is essential for
cognitive development. However, this association has not been demonstrated
empirically. This study aims to examine whether frequency of touchscreen use is
associated with sleep in infants and toddlers between 6 and 36 months of age. An
online survey was administered to 715 parents reporting on child media use (daily
exposure to TV and use of touchscreens), sleep patterns (night-time and daytime
sleep duration, sleep onset - time to fall asleep, and frequencies of night
awakenings). Structural equation models controlling for age, sex, TV exposure and
maternal education indicated a significant association between touchscreen use
and night-time sleep, daytime sleep and sleep onset. No significant effect was
observed for the number of night awakenings. To our knowledge, this is the first
report linking the use of touchscreen with sleep problems in infants and
toddlers. Future longitudinal studies are needed to clarify the direction of
effects and the mechanisms underlying these associations using detailed sleep
tracking.
PMID- 28406475
TI - Depletion of polycomb repressive complex 2 core component EED impairs fetal
hematopoiesis.
AB - Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex,
promotes the development of many organs by silencing ectopic transcription
program. However, currently little is known about the role of PRC2 in blood and
vascular development. In this study, we interrogated the function of embryonic
ectoderm development (EED), a core PRC2 component, in both endothelial and
hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre,
which catalyzes recombination in endothelial and hematopoietic lineages. Murine
EEDfl/fl;Tie2Cre (EEDCKO) embryos died at embryonic day (E) 13.5. We did not
observe structural abnormalities of blood vessels or cardiac valves, suggesting
that EED is dispensable in endothelial cells for initial steps of vascular
development. EEDCKO embryos were pale and had abnormal livers. Flow cytometry of
fetal liver cells showed that EED depletion significantly impeded erythroid
maturation. There was a corresponding increase in myeloid progenitors and
granulocytes and macrophages, suggesting an attenuated differentiation path in
myeloid lineages. Moreover, EED depletion impaired the generation of
hematopoietic stem cells. Collectively, our study demonstrates that within
Tie2Cre-recombined embryonic cells, EED is required for proper erythropoiesis and
for formation of hematopoietic progenitor and stem cells, but is dispensable for
endothelial lineage commitment and early vascular patterning.
PMID- 28406476
TI - WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in
human osteosarcoma.
AB - In recent years, much research has focused on the role of angiogenesis in
osteosarcoma, which occurs predominantly in adolescents and young adults. The
vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of
angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a
prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway
protein-1 (WISP-1) expression is associated with various cancers. However, the
function of WISP-1 in osteosarcoma angiogenesis is poorly understood. We
demonstrate a positive correlation between WISP-1 and VEGF-A expression in human
osteosarcoma. Moreover, we show that WISP-1 promotes VEGF-A expression in human
osteosarcoma cells, subsequently inducing human endothelial progenitor cell (EPC)
migration and tube formation. The focal adhesion kinase (FAK), Jun amino-terminal
kinase (JNK), and hypoxia-inducible factor (HIF)-1alpha signaling pathways were
activated after WISP-1 stimulation, while FAK, JNK, and HIF-1alpha inhibitors or
small interfering RNA (siRNA) abolished WISP-1-induced VEGF-A expression and
angiogenesis. In vitro and in vivo studies revealed down-regulation of microRNA
381 (miR-381) in WISP-1-induced VEGF-A expression and angiogenesis. Our findings
reveal that WISP-1 enhances VEGF-A expression and angiogenesis through the
FAK/JNK/HIF-1alpha signaling pathways, as well as via down-regulation of miR-381
expression. WISP-1 may be a promising target in osteosarcoma angiogenesis.
PMID- 28406477
TI - miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in
mice.
AB - microRNAs were recently suggested to contribute to the pathogenesis of
nonalcoholic fatty liver disease (NAFLD), a disease lacking specific
pharmacological treatments. In that regard, nuclear receptors are arising as key
molecular targets for the treatment of nonalcoholic steatohepatitis (NASH). Here
we show that, in a typical model of NASH-associated liver damage, microRNA-21
(miR-21) ablation results in a progressive decrease in steatosis, inflammation
and lipoapoptosis, with impairment of fibrosis. In a complementary fast food (FF)
diet NASH model, mimicking features of the metabolic syndrome, miR-21 levels
increase in both liver and muscle, concomitantly with decreased expression of
peroxisome proliferator-activated receptor alpha (PPARalpha), a key miR-21
target. Strikingly, miR-21 knockout mice fed the FF diet supplemented with
farnesoid X receptor (FXR) agonist obeticholic acid (OCA) display minimal
steatosis, inflammation, oxidative stress and cholesterol accumulation. In
addition, lipoprotein metabolism was restored, including decreased fatty acid
uptake and polyunsaturation, and liver and muscle insulin sensitivity fully
reinstated. Finally, the miR-21/PPARalpha axis was found amplified in liver and
muscle biopsies, and in serum, of NAFLD patients, co-substantiating its role in
the development of the metabolic syndrome. By unveiling that miR-21 abrogation,
together with FXR activation by OCA, significantly improves whole body metabolic
parameters in NASH, our results highlight the therapeutic potential of nuclear
receptor multi-targeting therapies for NAFLD.
PMID- 28406478
TI - The suppression of apoptosis by alpha-herpesvirus.
AB - Apoptosis, an important innate immune mechanism that eliminates pathogen-infected
cells, is primarily triggered by two signalling pathways: the death receptor
pathway and the mitochondria-mediated pathway. However, many viruses have evolved
various strategies to suppress apoptosis by encoding anti-apoptotic factors or
regulating apoptotic signalling pathways, which promote viral propagation and
evasion of the host defence. During its life cycle, alpha-herpesvirus utilizes an
elegant multifarious anti-apoptotic strategy to suppress programmed cell death.
This progress article primarily focuses on the current understanding of the
apoptosis-inhibition mechanisms of alpha-herpesvirus anti-apoptotic genes and
their expression products and discusses future directions, including how the anti
apoptotic function of herpesvirus could be targeted therapeutically.
PMID- 28406479
TI - Foot-and-mouth disease virus infection inhibits LGP2 protein expression to
exaggerate inflammatory response and promote viral replication.
AB - The role of the innate immune protein LGP2 (laboratory of genetics and physiology
2) in FMDV-infected cells remains unknown. Here, we demonstrate the antiviral
role of LGP2 during FMDV infection. FMDV infection triggered LGP2 mRNA expression
but reduced protein expression. Overexpression of LGP2 suppressed FMDV
replication, and the inflammatory response was significantly inhibited by LGP2 in
virus-infected cells. The N-terminal DExDc and the C-terminal regulatory domain
regions of LGP2 were essential for LGP2-mediated antiviral activity against FMDV.
Disruption of RNA recognition by LGP2 is suggested to abolish completely LGP2
mediated antiviral activity against FMDV. FMDV leader protein (Lpro), as well as
the 3Cpro and 2B proteins were determined to possess the ability to induce
reduction of LGP2 protein expression. 2B-induced reduction of LGP2 was
independent of cleavage of eukaryotic translation initiation factor 4 gamma; and
the proteasomes, lysosomes or caspase-dependent pathways were not involved in
this process. The C-terminal amino acids of 101-154 were essential for 2B-induced
reduction of LGP2 and upregulation of inflammatory response. Direct interaction
was demonstrated between LGP2 and 2B. Our results describe the antiviral role of
LGP2 against FMDV and a novel antagonistic mechanism of FMDV that is mediated by
2B protein.
PMID- 28406480
TI - WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7
mediated regulation of the Mdm2-p53 pathway.
AB - WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and
functions as a scaffold protein during telomerase assembly, Cajal body formation
and DNA double strand break repair. We have previously shown that WDR79 is
frequently overexpressed in cell lines and tissues derived from non-small cell
lung cancer (NSCLC) and it accelerates cell proliferation in NSCLC. However, the
detailed mechanism underlying the role of WDR79 in the proliferation of NSCLC
cells remains unclear. Here, we report the discovery of a molecular interaction
between WDR79 and USP7 and show its functional significance in linking the Mdm2
p53 pathway to the proliferation of NSCLC cells. We found that WDR79 colocalized
and interacted with USP7 in the nucleus of NSCLC cells. This event, in turn,
reduced the ubiquitination of Mdm2 and p53, thereby increasing the stability and
extending the half-life of the two proteins. We further found that the functional
effects of WDR79 depended upon USP7, because the knockdown of USP7 resulted in
their attenuation. Finally, we demonstrated that WDR79 promoted the proliferation
of NSCLC cells via USP7. Taken together, our findings reveal a novel molecular
function of WDR79 and may lead to broadly applicable and innovative therapeutic
avenues for NSCLC.
PMID- 28406481
TI - Liver receptor homolog-1 (NR5a2) regulates CD95/Fas ligand transcription and
associated T-cell effector functions.
AB - CD95/Fas ligand (FasL) is a cell death-promoting member of the tumor necrosis
factor family with important functions in the regulation of T-cell homeostasis
and cytotoxicity. In T cells, FasL expression is tightly regulated on a
transcriptional level involving a complex set of different transcription factors.
The orphan nuclear receptor liver receptor homolog-1 (LRH-1/NR5a2) is involved in
the regulation of development, lipid metabolism and proliferation and is
predominantly expressed in epithelial tissues. However, its expression in T
lymphocytes has never been reported so far. Based on in silico analysis, we
identified potential LRH-1 binding sites within the FASLG promoter. Here, we
report that LRH-1 is expressed in primary and secondary lymphatic tissues, as
well as in CD4+ and CD8+ T cells. LRH-1 directly binds to its binding sites in
the FASLG promoter, and thereby drives FASLG promoter activity. Mutations in the
LRH-1 binding sites reduce FASLG promoter activity. Pharmacological inhibition of
LRH-1 decreases activation-induced FasL mRNA expression, as well as FasL-mediated
activation-induced T-cell apoptosis and T-cell cytotoxicity. In a mouse model of
Concanavalin A-induced and FasL-mediated hepatitis pharmacological inhibition of
LRH-1 resulted in decreased hepatic FasL expression and a significant reduction
of liver damage. In summary, these data show for the first time LRH-1 expression
in T cells, its role in FASLG transcription and the potential of pharmacological
inhibition of LRH-1 in the treatment of FasL-mediated immunopathologies.
PMID- 28406483
TI - APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a
dedicated NADPH oxidase.
PMID- 28406482
TI - Cisplatin-enriching cancer stem cells confer multidrug resistance in non-small
cell lung cancer via enhancing TRIB1/HDAC activity.
AB - Chemotherapeutic agents are generally used as a frontline therapy for non-small
cell lung cancer (NSCLC). However, resistance to chemotherapy arises rapidly in
NSCLC, and the reasons for chemotherapy resistance have not been fully
determined. Here, we found cisplatin, but not paclitaxel and doxorubicin, induced
the enrichment of cancer stem cell (CSC) and conferred multidrug resistance in
NSCLC cell lines. In vivo study confirmed drug-resistant tumors displayed the
enhanced expressions of CSC transcription factors. Mechanistically, cisplatin
treatment resulted in C/EBP-beta-dependent increasing of TRIB1. The crucial role
of TRIB1 in cisplatin-induced enrichment of CSC and drug resistance was verified
by knockdown TRIB1. Interestingly, cisplatin treatment also contributed to the
increasement of HDAC, the interaction of TRIB1 with HDAC, and inactivation of
p53. Similarly, the silencing of HDAC led to reduction of cisplatin-induced CSC,
and combined knockdown of HDAC and TRIB1 exhibited enhanced effect. Additionally,
the combination of HDAC inhibitor and cisplatin showed a reinforced antitumor
action in NSCLC cell lines with TRIB1-dependent manner and remarkably shrink
tumors in xenograft models. Moreover, cisplatin-treated NSCLC patients with high
levels of TRIB1 exhibited a significantly poorer prognosis. Our findings
illustrate a novel perspective in the evolution of chemotherapy resistance and
provide a promising approach for the treatment of patients with NSCLC.
PMID- 28406484
TI - Induction of labor by Foley catheter compared with spontaneous onset of labor
after previous cesarean section: a cohort study.
AB - OBJECTIVE: To evaluate the safety of induction of labor (IOL) with Foley catheter
(FC) in women with a history of previous cesarean section (CS) and to assess risk
factors for repeat CS and adverse maternal outcomes. STUDY DESIGN: Cohort study
of 1559 women with a history of previous CS in Helsinki University Hospital,
Finland between 2013 and 2014. RESULTS: Three hundred and sixty-one women (23.2%)
underwent IOL by FC and 1198 (76.8%) had spontaneous onset of labor. The rate of
repeat CS was higher in women undergoing IOL (38% vs 20.2%; P<0.001). The overall
rate of uterine rupture was 0.3% in induced labor and 0.8% in spontaneous onset
of labor (P=0.47). Adverse maternal outcomes were not significantly different.
The intrapartum and postpartum infection rates were higher in women undergoing
IOL compared with spontaneous onset of labor (6.1% vs 1.8%; P>0.001 and 5.3% vs
1.3%; P<0.001, respectively). CONCLUSION: FC appears safe and effective method
for IOL in women with a history of previous CS.
PMID- 28406485
TI - Cardiac hemodynamics before, during and after elective cesarean section under
spinal anesthesia in low-risk women.
AB - OBJECTIVE: The aim of this study was to describe maternal central hemodynamic
parameters before and during delivery as well at the early puerperium in healthy
women undergoing elective cesarean section (CS) at term. STUDY DESIGN: The
noninvasive Cardiac System (NICaS, NI Medical, Petah-Tikva, Israel) is a regional
impedance device that measures cardiac output (CO) and its derivatives with a
good correlation with the gold standard Swan-Ganz catheter. We performed a
prospective longitudinal study of healthy women with a singleton pregnancy at
term. Maternal hemodynamic parameters were assessed by the NICaS at six time
points: a few minutes before undergoing an elective CS, immediately after
receiving spinal anesthesia, immediately after delivery of the fetus and
placenta, after abdominal fascia closure, and within 24 to 36 and 48 to 72 h
postpartum. RESULT: Sixty-one consenting women were recruited during the study
period (January 2015 to June 2015). Baseline (pre-CS) mean arterial pressure
(MAP) was 87.7+/-7.9 mm Hg, baseline CO was 7.5+/-1.7 l per min and baseline
total peripheral resistance (TPR) was 994+/-301 dyne * s per cm5. After spinal
anesthesia CO significantly increased by 13%, no significant changes were
observed in MAP or TPR. Immediately after delivery, a nadir for all parameters
was reached: MAP and TPR were significantly reduced by 8% and 26%, respectively
(comparing to pre-CS), and CO further increased by 9% (24% comparing to pre-CS).
After fascia closure, partial recoveries of all parameters were observed. Twenty
four to thirty-six hours postpartum MAP returned to pre-CS values, while CO and
TPR reached -9% and +11% comparing to baseline, respectively. None of the
parameters differed significantly between 24 to 36 and 48 to 72 h postpartum.
CONCLUSION: Significant hemodynamic changes (reduction of TPR and increase of CO)
take place at the time of delivery of fetus and placenta. Knowledge of normal
hemodynamic values using a reliable noninvasive technique during various stages
of pregnancy and the postpartum period is feasible, and might assist clinicians
in assessing the level of patient deviation from expected cardiac performance,
especially in high-risk women.
PMID- 28406486
TI - Promoting teamwork may improve infant care processes during delivery room
management: Florida perinatal quality collaborative's approach.
AB - BACKGROUND: LOCAL PROBLEM: Inadequate understanding of compliance with
standardized evidence-based DR management. INTERVENTIONS: Promote inter
professional teamwork and a bundle of interventions focusing on resuscitation
team roles, equipment check, and debriefing using QI methodology. Optimize
delivery room (DR) management to achieve 10-min SPO2 targets, delayed-cord
clamping (DCC), team role assignment and debriefings in >50% of deliveries, and
achieve normothermia in >75% of infants. METHODS: Over 15 months (Epoch 1 to 5),
nine Florida hospitals implemented a DR management plan for infants <31 weeks
gestational age or <1500 g (N=814) using quality improvement methodology.
RESULTS: There was increased compliance of DCC (36 to 66%), role assignment (53
to 98%), debriefing rates (33 to 76%) and having all seven pre-delivery
preparedness components fulfilled (34 to 75%). There were no significant
improvements in admission temperatures or SPO2 targeting. When 7 vs 0 items of
pre-delivery preparedness were completed, we saw improvements in thermoregulation
(57% vs 72%), SPO2 targeting (60% vs 78%) and DCC compliance (43 to 67%).
CONCLUSION: Promoting teamwork by increasing pre-delivery preparedness is
associated with improvement of thermoregulation, SPO2 targeting and DCC
compliance.
PMID- 28406487
TI - The effect of maternal habitus on macronutrient content of human milk colostrum.
AB - OBJECTIVE: There is a paucity of studies on the impact of maternal body mass
index (BMI) on macronutrient content of human milk colostrum (HMC). The objective
of this study was to compare macronutrient content of HMC in healthy women of
term infants in relation to their BMI. We hypothesized that mother habitus
influences human milk colostrum content. METHOD: Colostrum was collected from 109
healthy mothers of hospitalized healthy term infants divided into four
prepregnancy BMI groups: 12 underweight, 59 normal weight, 20 overweight, and 18
obese women between 24 and 72 h after birth. Macronutrient content was measured
using mid-infrared spectroscopy. RESULTS: There were no significant differences
in macronutrients between the BMI groups. We performed four separate stepwise
backward multiple regression analyses taking into account fat, carbohydrate,
protein or energy content as dependent variables and maternal BMI, parity,
gestational age, infant gender, maternal age, maternal education, mode of
delivery and time postdelivery. In these analyses, fat, carbohydrate and energy
content were not related to maternal BMI, while protein content was significantly
and positively correlated with BMI (P=0.008) and negatively correlated with
gestational age (P=0.004) and time postdelivery (P<0.001). Colostrum carbohydrate
content was positively correlated with parity. Colostrum fat and energy content
were negatively correlated with maternal age and positively correlated with
parity. CONCLUSION: Most macronutrient and energy content of colostrum are
unaffected by prepregnancy maternal BMI, with the exception of protein content
that is positively related to maternal BMI.
PMID- 28406488
TI - Making genomic medicine evidence-based and patient-centered: a structured review
and landscape analysis of comparative effectiveness research.
AB - Comparative effectiveness research (CER) in genomic medicine (GM) measures the
clinical utility of using genomic information to guide clinical care in
comparison to appropriate alternatives. We summarized findings of high-quality
systematic reviews that compared the analytic and clinical validity and clinical
utility of GM tests. We focused on clinical utility findings to summarize CER
derived evidence about GM and identify evidence gaps and future research needs.
We abstracted key elements of study design, GM interventions, results, and study
quality ratings from 21 systematic reviews published in 2010 through 2015. More
than half (N = 13) of the reviews were of cancer-related tests. All reviews
identified potentially important clinical applications of the GM interventions,
but most had significant methodological weaknesses that largely precluded any
conclusions about clinical utility. Twelve reviews discussed the importance of
patient-centered outcomes, although few described evidence about the impact of
genomic medicine on these outcomes. In summary, we found a very limited body of
evidence about the effect of using genomic tests on health outcomes and many
evidence gaps for CER to address.Genet Med advance online publication 13 April
2017.
PMID- 28406490
TI - ACMG secondary findings 2.0.
PMID- 28406489
TI - Consensus recommendation for a diagnostic guideline for acid sphingomyelinase
deficiency.
AB - : Disclaimer:This diagnostic guideline is intended as an educational resource and
represents the opinions of the authors, and is not representative of
recommendations or policy of the American College of Medical Genetics and
Genomics (ACMG). The information should be considered a consensus based on expert
opinion, as more comprehensive levels of evidence were not available in the
literature in all cases. BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a
rare, progressive, and often fatal lysosomal storage disease. The underlying
metabolic defect is deficiency of the enzyme acid sphingomyelinase that results
in progressive accumulation of sphingomyelin in target tissues. ASMD manifests as
a spectrum of severity ranging from rapidly progressive severe neurovisceral
disease that is uniformly fatal to more slowly progressive chronic neurovisceral
and chronic visceral forms. Disease management is aimed at symptom control and
regular assessments for multisystem involvement. PURPOSE AND METHODS: An
international panel of experts in the clinical and laboratory evaluation,
diagnosis, treatment/management, and genetic aspects of ASMD convened to review
the evidence base and share personal experience in order to develop a guideline
for diagnosis of the various ASMD phenotypes. CONCLUSIONS: Although care of ASMD
patients is typically provided by metabolic disease specialists, the guideline is
directed at a wide range of providers because it is important for primary care
providers (e.g., pediatricians and internists) and specialists (e.g.,
pulmonologists, hepatologists, and hematologists) to be able to identify
ASMD.Genet Med advance online publication 13 April 2017.
PMID- 28406491
TI - Response to Biesecker.
PMID- 28406492
TI - Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential
of Polyps.
PMID- 28406493
TI - Genetic Characterization and Influence on Inflammatory Bowel Disease Expression
in a Diverse Hispanic South Florida Cohort.
AB - OBJECTIVES: Hispanics represent an understudied inflammatory bowel disease (IBD)
population. Prior studies examining genetic predisposition to IBD in Hispanics
are limited. In this study, we examined whether European-derived IBD variants
confer risk in Hispanics and their influence on IBD phenotype in Hispanics
compared to non-Hispanic whites (NHW). METHODS: Self-identified Hispanics and
NHWs with IBD were included. Hispanic controls were included for our genetic
analyses. We performed single-variant testing at previously identified Crohn's
disease (CD) and ulcerative colitis (UC) IBD variants in Hispanic cases and
controls. These risk variants were used to compute individual genetic risk
scores. Genetic risk scores and phenotype associations were compared between
Hispanic and NHW. RESULTS: A total of 1,115 participants were included: 698
controls and 417 IBD patients (230 Hispanics). We found evidence of association
within our Hispanic cohort at 22 IBD risk loci, with ~76% of the risk loci
demonstrating over-representation of the European risk allele; these included
loci corresponding to IL23R and NOD2 genes. CD genetic risk score for Hispanics
(199.67) was similar to the score for NHW (200.33), P=0.51; the same was true in
UC. Genetic risk scores did not predict IBD phenotype or complications in
Hispanics or NHW except for a younger age of CD onset in Hispanics (P=0.04).
CONCLUSIONS: This study highlights the fundamental importance of these loci in
IBD pathogenesis including in our diverse Hispanic population. Future studies
looking at non-genetic mechanisms of disease are needed to explain differences in
age of presentation and phenotype between Hispanics and NHW.
PMID- 28406494
TI - Laser Capture Microdissection of Pancreatic Acinar Cells to Identify Proteomic
Alterations in a Murine Model of Caerulein-Induced Pancreatitis.
AB - OBJECTIVES: Chronic pancreatitis (CP) is characterized by inflammation and
fibrosis of the pancreas, leading to pain, parenchymal damage, and loss of
exocrine and endocrine function. There are currently no curative therapies;
diagnosis remains difficult and aspects of pathogenesis remain unclear. Thus,
there is a need to identify novel biomarkers to improve diagnosis and understand
pathophysiology. We hypothesize that pancreatic acinar regions contain proteomic
signatures relevant to disease processes, including secreted proteins that could
be detected in biofluids. METHODS: Acini from pancreata of mice injected with or
without caerulein were collected using laser capture microdissection followed by
mass spectrometry analysis. This protocol enabled high-throughput analysis that
captured altered protein expression throughout the stages of CP. RESULTS: Over
2,900 proteins were identified, whereas 331 were significantly changed >=2-fold
by mass spectrometry spectral count analysis. Consistent with pathogenesis, we
observed increases in proteins related to fibrosis (e.g., collagen, P<0.001),
several proteases (e.g., trypsin 1, P<0.001), and altered expression of proteins
associated with diminished pancreas function (e.g., lipase, amylase, P<0.05). In
comparison with proteomic data from a public data set of CP patients, a
significant correlation was observed between proteomic changes in tissue from
both the caerulein model and CP patients (r=0.725, P<0.001). CONCLUSIONS: This
study illustrates the ability to characterize proteome changes of acinar cells
isolated from pancreata of caerulein-treated mice and demonstrates a relationship
between signatures from murine and human CP.
PMID- 28406495
TI - Quantitative 3D structured illumination microscopy of nuclear structures.
AB - 3D structured illumination microscopy (3D-SIM) is the super-resolution technique
of choice for multicolor volumetric imaging. Here we provide a validated sample
preparation protocol for labeling nuclei of cultured mammalian cells, image
acquisition and registration practices, and downstream image analysis of nuclear
structures and epigenetic marks. Using immunostaining and replication labeling
combined with image segmentation, centroid mapping and nearest-neighbor analyses
in open-source environments, 3D maps of nuclear structures are analyzed in
individual cells and normalized to fluorescence standards on the nanometer scale.
This protocol fills an unmet need for the application of 3D-SIM to the
technically challenging nuclear environment, and subsequent quantitative analysis
of 3D nuclear structures and epigenetic modifications. In addition, it
establishes practical guidelines and open-source solutions using ImageJ/Fiji and
the TANGO plugin for high-quality and routinely comparable data generation in
immunostaining experiments that apply across model systems. From sample
preparation through image analysis, the protocol can be executed within one week.
PMID- 28406496
TI - Strategic and practical guidelines for successful structured illumination
microscopy.
AB - Linear 2D- or 3D-structured illumination microscopy (SIM or3D-SIM, respectively)
enables multicolor volumetric imaging of fixed and live specimens with
subdiffraction resolution in all spatial dimensions. However, the reliance of SIM
on algorithmic post-processing renders it particularly sensitive to artifacts
that may reduce resolution, compromise data and its interpretations, and drain
resources in terms of money and time spent. Here we present a protocol that
allows users to generate high-quality SIM data while accounting and correcting
for common artifacts. The protocol details preparation of calibration bead slides
designed for SIM-based experiments, the acquisition of calibration data, the
documentation of typically encountered SIM artifacts and corrective measures that
should be taken to reduce them. It also includes a conceptual overview and
checklist for experimental design and calibration decisions, and is applicable to
any commercially available or custom platform. This protocol, plus accompanying
guidelines, allows researchers from students to imaging professionals to create
an optimal SIM imaging environment regardless of specimen type or structure of
interest. The calibration sample preparation and system calibration protocol can
be executed within 1-2 d.
PMID- 28406497
TI - Correction: Rapid fabrication of functionalised poly(dimethylsiloxane) microwells
for cell aggregate formation.
AB - Correction for 'Rapid fabrication of functionalised poly(dimethylsiloxane)
microwells for cell aggregate formation' by A. Forget et al., Biomater. Sci.,
2017, 5, 828-836.
PMID- 28406498
TI - Atomic layer deposition of Cu(i) oxide films using Cu(ii) bis(dimethylamino-2
propoxide) and water.
AB - To grow films of Cu2O, bis-(dimethylamino-2-propoxide)Cu(ii), or Cu(dmap), is
used as an atomic layer deposition precursor using only water vapor as a co
reactant. Between 110 and 175 degrees C, a growth rate of 0.12 +/- 0.02 A per
cycle was measured using an in situ quartz crystal microbalance (QCM). X-ray
photoelectron spectroscopy (XPS) confirms the growth of metal-oxide films
featuring Cu(i).
PMID- 28406499
TI - Phospholipid-mimic oxaliplatin prodrug liposome for treatment of the metastatic
triple negative breast cancer.
AB - A phospholipid-mimic oxaliplatin prodrug (Oxalipid) was synthesized, which could
self-assemble into a liposomal nanostructure with a drug loading ratio as high as
27 wt%. Compared to free oxaliplatin, the resulting Oxalipid liposome displayed
elongated blood circulation, increased tumor accumulation and improved anticancer
efficacy against the metastatic triple negative breast cancer (TNBC).
PMID- 28406500
TI - Stability, transport and ecosystem effects of graphene in water and soil
environments.
AB - Graphene nanomaterials (GMs), such as graphene oxide (GO) and reduced graphene
oxide (rGO), have been widely applied in various fields. Due to the rapid
increase in production and application, the inevitable release of GMs into water
and soil environments poses potential health and ecosystem risks. Upon exposure,
the behavior, transport, and fate of GMs may be altered after interacting with
the relevant environmental conditions. GMs can affect the microbial communities
as well. Thus, it is imperative to understand the interaction between the GMs and
the environmental systems for predicting their risks. For this purpose, this
review highlights the influence of the most relevant environmental factors on the
stability, aggregation, and transformation of GMs in aquatic environments.
Moreover, the transport of GMs and microbial communities changes have also been
presented based on the recent findings. To the best of our knowledge, this review
covered most of the recent related studies and will allow for accurate
predictions of the fate and risks associated with GMs. In consideration of the
diversity of GMs and the complexity of environmental factors, further studies
should be focused on their inherent properties and amicable development.
PMID- 28406501
TI - Culture-dependent enumeration methods failed to simultaneously detect
disinfectant-injured and genetically modified Escherichia coli in drinking water.
AB - Underestimation of Escherichia coli in drinking water, an indicator microorganism
of sanitary risk, may result in potential risks of waterborne diseases. However,
the detection of disinfectant-injured or genetically modified (GM) E. coli has
been largely overlooked so far. To evaluate the accuracy of culture-dependent
enumeration with regard to disinfectant-injured and GM E. coli, chlorine- or
ozone-injured wild-type (WT) and GM E. coli were prepared and characterized.
Then, water samples contaminated with these E. coli strains were assayed by four
widely used methods, including lactose tryptose broth-based multiple-tube
fermentation (MTF), m-endo-based membrane filtration method (MFM), an enzyme
substrate test (EST) known as Colilert, and Petrifilm-based testing slip method
(TSM). It was found that MTF was the most effective method to detect disinfectant
injured WT E. coli (with 76.9% trials detecting all these bacteria), while this
method could not effectively detect GM E. coli (with uninjured bacteria
undetectable and a maximal detection rate of 21.5% for the injured). The EST was
the only method which enabled considerable enumeration of uninjured GM E. coli,
with a detection rate of over 93%. However, the detection rate declined to lower
than 45.4% once the GM E. coli was injured by disinfectants. The MFM was invalid
for both disinfectant-injured and GM E. coli. This is the first study to report
the failure of these commonly used enumeration methods to simultaneously detect
disinfectant-injured and GM E. coli. Thus, it highlights the urgent requirement
for the development of a more accurate and versatile enumeration method which
allows the detection of disinfectant-injured and GM E. coli on the assessment of
microbial quality of drinking water.
PMID- 28406503
TI - Effect of fibrous separators on the performance of lithium-sulfur batteries.
AB - In this paper we systematically investigated effect of separator morphology on
the performance of Li-S batteries. We tested two kinds of commercially available
non-woven fibrous separators made of polypropylene in conjunction with trilayer
PP/PE/PP porous separator. Among the non-woven separators, the fibers of the
separator of first kind are rough and more acidic than the fibers of the
separator of second art, which are smooth. It was found that batteries with
smooth separator demonstrate higher Coulombic efficiency, higher
charging/discharging capacity and better cycling stability. We attribute better
performance of batteries with smooth fibers of separators to lower acidity than
that of rough fibers. We believe that negatively charged polysulfides are unable
to adsorb on more acidic rough fibers and diffuse readily to lithium electrode.
In contrast, polysulfides are able to adsorb on the surface of less acidic smooth
fibers that reduces their polysulfides shuttle and rapid decay of battery
capacity. Strategic deployment of non-woven Freudenberg and Celgard separator in
combination leads to high active mass utilization, superior wettability, reduced
short circuit tendency caused by dendritic growth and slower capacity decay.
PMID- 28406502
TI - Self-regulatory factors of embryonic stem cells in co-culture with stromal cells
enhance neural differentiation.
AB - Embryonic stem cells (ESCs), due to their intrinsic capability to generate
somatic cells of all three germ layers, are potential sources of neural cells for
cell replacement therapies. However, the empirical differentiation protocols and
the lack of mechanistic understanding of the neural differentiation of ESCs have
limited the utility of ESCs as a developmental model or as a cell source for
neural cell populations for replacement therapies. Co-culturing ESCs with stromal
cells is one of the extensively used methods to induce neural differentiation.
Despite several studies to identify neural inducing factors in stromal cell
induced neural differentiation, the self-regulatory effects of ESCs in the neural
differentiation process remain unexplored. For the first time, we elucidate the
self-regulatory role of mESCs in their neural cell differentiation by
supplementing conditioned media from differentiating mESCs to mESC-PA6 co
cultures and quantitatively evaluating the change in neural differentiation.
Moreover, we use statistical tools to analyze the expression of various growth
and trophic factors and distinguish the factors produced primarily by PA6 cells
versus mESCs in co-culture. We observe that addition of the medium containing
mESC-secreted factors to a single mESC colony co-cultured with PA6 cells
significantly enhances the neural differentiation of mESCs compares to the medium
extracted from the stromal cells only. Hierarchical clustering of gene expression
data from PA6 and co-cultured mESCs segregates two groups of factors that are
produced by the stromal cells and differentiating mESCs. Identifying the major
soluble factors that drive and regulate the neural differentiation process in the
mESC-PA6 co-culture niche will help understand molecular mechanisms of neural
development. Moreover, it can be a major step toward developing novel protocols
to differentiate stem cells with mESC derived factor supplementation without
using feeder cells and with greater efficiency compared to existing approaches.
PMID- 28406504
TI - A molecular-scale portrait of domain imaging in organic surfaces.
AB - Progress in the general understanding of structure-property relationships in
organic devices requires experimental tools capable of imaging structural
details, such as molecular packing or domain attributes, on ultra-thin films. An
operation mode of scanning force microscopy, related to friction force microscopy
(FFM) and known as transverse shear microscopy (TSM), has demonstrated the
ability to reveal the orientation of crystalline domains in organic surfaces with
nanometer resolution. In spite of these promising results, numerous questions
remain about the physical origin of the TSM domain imaging mechanism. Taking as a
benchmark a PTCDI-C8 sub-monolayer, we demonstrate experimentally and
theoretically that such a mechanism is the same atomic scale stick-slip ruling
FFM leading to the angular dependence of both signals. Lattice-resolved images
acquired on top of differently oriented PTCDI-C8 molecular domains are crucial to
permit azimuthal sampling, without the need for sample rotation. The simulations
reveal that, though the surface crystallography is the direct cause of the FFM
and TSM signals, the manifestation of anisotropy will largely depend on the
amplitude of the surface potential corrugation as well as on the temperature.
This work provides a novel nanoscale strategy for the quantitative analysis of
organic thin films based on their nanotribological response.
PMID- 28406505
TI - One-step formation of dihydrofuranoindoline cores promoted by a hypervalent
iodine reagent.
AB - Treatment of various substituted anilines containing a sulfonyl group in the
presence of a hypervalent iodine reagent, a perfluorinated alcohol and furan
promotes a formal dearomatizing [2 + 3] cycloaddition process, leading to a
dihydrofuranoindoline core in useful yields. Thereafter, these functionalized
systems can be used for further transformations, yielding potential key
intermediates for the total synthesis of complex natural products.
PMID- 28406506
TI - Production and characterization of curcumin microcrystals and evaluation of the
antimicrobial and sensory aspects in minimally processed carrots.
AB - Nontoxic conserving agents are in demand by the food industry due to consumers
concern about synthetic conservatives, especially in minimally processed food.
The antimicrobial activity of curcumin, a natural phenolic compound, has been
extensively investigated but hydrophobicity is an issue when applying curcumin to
foodstuff. The objective of this work was to evaluate curcumin microcrystals as
an antimicrobial agent in minimally processed carrots. The antimicrobial activity
of curcumin microcrystals was evaluated in vitro against Gram-positive (Bacillus
cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli and
Pseudomonas aeruginosa) microorganisms, showing a statistically significant (p <
0.05) decrease in the minimum inhibitory concentration compared to in natura,
pristine curcumin. Curcumin microcrystals were effective in inhibiting
psychrotrophic and mesophile microorganisms in minimally processed carrots.
Sensory analyses were carried out showing no significant difference (p < 0.05)
between curcumin microcrystal-treated carrots and non-treated carrots in
triangular and tetrahedral discriminative tests. Sensory tests also showed that
curcumin microcrystals could be added as a natural preservative in minimally
processed carrots without causing noticeable differences that could be detected
by the consumer. One may conclude that the analyses of the minimally processed
carrots demonstrated that curcumin microcrystals are a suitable natural compound
to inhibit the natural microbiota of carrots from a statistical point of view.
PMID- 28406507
TI - Achieving yellow emission by varying the donor/acceptor units in rod-shaped
fluorenyl-alkynyl based pi-conjugated oligomers and their binuclear gold(i)
alkynyl complexes.
AB - Fluorenyl-alkynyl based pi-conjugated rod-shaped oligomers bearing different
central aromatic moieties and functionalizable di-alkynyl termini, such as H
[triple bond, length as m-dash]-Fl-[triple bond, length as m-dash]-Fl-[triple
bond, length as m-dash]-Fl-[triple bond, length as m-dash]-H (OH1), H-[triple
bond, length as m-dash]-Fl-[triple bond, length as m-dash]-Btz-[triple bond,
length as m-dash]-Fl-[triple bond, length as m-dash]-H (OH2) and H-[triple bond,
length as m-dash]-Fl-[triple bond, length as m-dash]-Btd-[triple bond, length as
m-dash]-Fl-[triple bond, length as m-dash]-H (OH3) where Fl = 9,9
dioctylfluorene, Btz = N-hexylbenzotriazole, and Btd = benzothiadiazole, were
successfully synthesized by a Pd(0) catalyzed Stille coupling protocol. Electron
withdrawing benzothiadiazole and benzotriazole as strong to moderate acceptors
and fluorene as the donor have been incorporated to adjust the Donor-Acceptor (D
A) strength for fine-tuning the bandgap (Eg) as well as the emission wavelength.
The corresponding digold(i) sigma-complexes (PPh3)Au-[triple bond, length as m
dash]-Fl-[triple bond, length as m-dash]-Fl-[triple bond, length as m-dash]-Fl
[triple bond, length as m-dash]-Au(PPh3) (OM1), (PPh3)Au-[triple bond, length as
m-dash]-Fl-[triple bond, length as m-dash]-Btz-[triple bond, length as m-dash]-Fl
[triple bond, length as m-dash]-Au(PPh3) (OM2) and (PPh3)Au-[triple bond, length
as m-dash]-Fl-[triple bond, length as m-dash]-Btd-[triple bond, length as m-dash]
Fl-[triple bond, length as m-dash]-Au(PPh3) (OM3) have also been prepared by a
reaction of Au(PPh3)Cl and methanolic NaOMe in DCM with the corresponding alkynyl
functionalized oligomers to take advantage of the heavy-atom effect on their
emissive properties. The synthesized rod-shaped pi-conjugated fluorene based
oligomers and their binuclear Au(i) sigma-complexes have been unambiguously
characterized by various spectroscopic tools such as FTIR and multinuclear NMR as
well as MALDI-TOF and CHN analyses. The absorption and emission spectral studies
exhibited a progressive red shift with increasing the electron withdrawing
character of the central aromatic unit. The rod-like oligomers having alkynyl
termini and the corresponding digold(i) complexes are found to be blue, cyan and
yellow emissive, demonstrating the fine-tuning of the emission wavelength. Most
importantly, the fluorene based pi-conjugated yellow light emitters OH3 and OM3
are successfully achieved by varying the donor/acceptor moiety to the fluorenyl
alkynyl backbone. The digold(i) diacetylide organometallic wires exhibit
phosphorescence at 77 K in degassed CH2Cl2 due to the efficient intersystem
crossing from the S1 to the T1 excited state as induced by heavy atoms.
PMID- 28406508
TI - Integration of digital microfluidics with whispering-gallery mode sensors for
label-free detection of biomolecules.
AB - We present a multi-sensor chip comprising an array of whispering-gallery mode
(WGM) micro-goblet lasers integrated into a digital microfluidic (DMF) system. In
contrast to earlier demonstrations, the lasers are fabricated from dye-doped poly
methyl methacrylate (PMMA) at low cost using spin-coating, mask-based optical
lithography, wet chemical etching, and thermal reflow techniques. Pumping and
read-out of the devices is accomplished via simple free-space optics, thereby
allowing large-scale sensor arrays to be addressed. We demonstrate the viability
of the system by bulk refractive index-sensing and by measuring the specific
binding of streptavidin to a biotinylated sensor surface. This is the first time
that optical cavities are used for label-free detection of biomolecules in a DMF
system. This approach can be extended to a versatile detector platform that
targets a wide range of clinically relevant biomolecules.
PMID- 28406509
TI - A divergent and metal free synthesis of sulfoximine tethered imidazoles,
imidazopyridines, imidazothiazoles, imidazobenzothiazines, thiazoles and
selenazoles.
AB - A divergent and metal free approach has been successfully developed for the
synthesis of sulfoximine tethered heterocycles. A key alpha-bromoalkanone
intermediate 3b has been reported for the first time. Various sulfoximine
tethered imidazoles, imidazopyridines, thiozoloimidazoles, imidazobenzothiazines,
thiazoles and selenazoles are made from this common sulfoximine building block.
PMID- 28406510
TI - Composition dependent magnetic and ferroelectric properties of hydrothermally
synthesized GdFe1-xCrxO3 (0.1 <= x <= 0.9) perovskites.
AB - The hydrothermal synthesis and magnetic, dielectric and ferroelectric property
characterization of ABO3-perovskite GdFe1-xCrxO3 (0 < x < 1) are reported. The
mineralizer KOH plays a critical role in the perovskite structure of the sample.
The Fe/Cr ratio of the final crystal is controlled by the alkalinity in the
initial reaction mixtures. The lattice parameters and magnetic ordering
transition temperature have a close relationship with the Fe/Cr ratio. The
temperature dependent magnetic properties of GdFe1-xCrxO3 (0 < x < 1) samples
show a close relationship with substituent ratios of Cr3+. The occurrence of
ferromagnetic behavior in all of the as-prepared samples comes from the
coexistence of canted-antiferromagnetism due to the double exchange effect of Fe
O-Fe and Cr-O-Cr and ferromagnetism due to superexchange interaction of Fe-O-Cr.
A large spontaneous polarization was observed in GdFe1-xCrxO3 at room
temperature, exhibiting a clear ferroelectric hysteresis loop, which indicates
the ferroelectric behavior in this system. This work not only provides an
effective route to the controllable synthesis of B-site doped REFe1-xCrxO3
perovskite structure materials, but also presents a comprehensive study of the
tunable effect of ionic doping on ferroelectric properties.
PMID- 28406511
TI - Synthesis of 2,3-dihydro-1H-pyrroles by intramolecular cyclization of N-(3
butynyl)-sulfonamides.
AB - Hydroamination of 3-butynamine derivatives to give non-aromatic 2,3
dihydropyrroles was achieved by using PdCl2 or AuCl as the catalyst. With
microwave-assisted heating, up to 92% isolated yield was obtained from this
intramolecular 5-endo-dig cyclisation. The cyclopentane- and cyclohexane-fused
2,3-dihydropyrroles were transformed into the corresponding N-tosyl-pyrrolidine-2
carboxylic acids.
PMID- 28406512
TI - On the lubricity of transition metal dichalcogenides: an ab initio study.
AB - Owing to specific characteristics engendered by their lamellar structures,
transition metal dichalcogenides are posited as being some of the best dry
lubricants available. Herein, we report a density functional investigation into
the sliding properties and associated phenomena of these materials. Calculated
potential energy and charge transfer profiles are used to highlight the
dependence of shear strength on chemical composition and bilayer orientation
(sliding direction). Furthermore, our calculations underscore the intrinsic
relationship between incommensurate crystals and the oft-touted superlubric
behaviour of molybdenum disulfide.
PMID- 28406513
TI - Cooperative spin-crossover transition from three-dimensional purely pi-stacking
interactions in a neutral heteroleptic azobisphenolate FeIII complex with a N3O3
coordination sphere.
AB - A novel neutral heteroleptic FeIII complex from two kinds of pi-extended
tridentate ligands was designed and prepared. The pi-ligands formed a three
dimensional purely pi-stacking interaction network. The present complex proved to
be the first neutral spin-crossover (SCO) FeIII complex with a N3O3 coordination
sphere exhibiting an abrupt SCO transition with a thermal hysteresis of 10 K and
the light-induced excited spin-state trapping effect.
PMID- 28406514
TI - Toward artifact-free data in Hadamard transform-based double multiplexing of ion
mobility-Orbitrap mass spectrometry.
AB - The integration of ion mobility spectrometry (IMS) with a trap-based mass
spectrometer (MS) such as Orbitrap using the dual gate approach suffers from low
duty cycle. Efforts to improve the duty cycle involve the utilization of Hadamard
transform-based double multiplexing which significantly improves the signal-to
noise ratio and duty cycle of the ion mobility-Orbitrap mass spectrometry (IM
Orbitrap MS) platform. However, artifacts and noise in the demultiplexed data
significantly reduce the data quality and negate the benefits of multiplexing. We
propose a new approach that identifies the true IM peaks and helps in eliminating
the artifacts in the demultiplexed data leading to a decrease in false
identifications in subsequent data processing. After the application of the
algorithm, the quality of the IM-Orbitrap MS measurements was greatly improved
because of the reduction in artifacts.
PMID- 28406515
TI - Integration of community structure data reveals observable effects below sediment
guideline thresholds in a large estuary.
AB - The sustainable management of estuarine and coastal ecosystems requires robust
frameworks due to the presence of multiple physical and chemical stressors. In
this study, we assessed whether ecological health decline, based on community
structure composition changes along a pollution gradient, occurred at levels
below guideline threshold values for copper, zinc and lead. Canonical analysis of
principal coordinates (CAP) was used to characterise benthic communities along a
metal contamination gradient. The analysis revealed changes in benthic community
distribution at levels below the individual guideline values for the three
metals. These results suggest that field-based measures of ecological health
analysed with multivariate tools can provide additional information to single
metal guideline threshold values to monitor large systems exposed to multiple
stressors.
PMID- 28406516
TI - Enantioselective total synthesis of colomitides and their absolute configuration
determination and structural revision.
AB - An efficient stereoselective synthetic approach to colomitides, 2,7
dioxabicyclo[3.2.1]octane-type natural products, is reported. Key steps are a
stereocontrolled aldol reaction and a gold-catalyzed cycloisomerization. This
synthetic strategy has been applied for the first asymmetric total synthesis of
the proposed colomitides and their possible diastereomers. Comparison of their 1H
and 13C NMR spectra and specific rotations with those of the natural product
revealed that the structure of colomitide A should be revised to 1c, and that the
absolute stereochemistries of colomitides A and B are 2'R,4R,5R,8S,1R and
2'R,4S,5R,8S,1R.
PMID- 28406517
TI - Biochemical studies of inositol N-acetylglucosaminyltransferase involved in
mycothiol biosynthesis in Corynebacterium diphtheria.
AB - Mycothiol (MSH) is the predominant low molecular weight thiol produced by
actinomycetes, and it plays a pivotal role in the bacterial detoxication process.
1L-myo-Inositol-1-phosphate (1L-Ins-1-P) alpha-N-acetylglucosaminyltransferase
(GlcNAc-T), known as MshA, is the only glycosyltransferase involved in MSH
biosynthesis. In this work, the MshA from Corynebacterium diphtheria, named as
CdMshA, was expressed, purified, and studied in detail. Its enzymatic activity to
transfer GlcNAc to 1L-Ins-1-P was confirmed by the isolation and rigorous
characterization of its reaction product 3-phospho-1-d-myo-inositol-2-acetamido-2
deoxy-alpha-d-glucopyranoside. CdMshA was shown to accept only UDP-GlcNAc and 1L
Ins-1-P as its substrates among various tested glycosyl donors, such as UDP
GlcNAc, UDP-Gal, UDP-Glc, UDP-GalNAc and UDP-GlcA, and glycosyl acceptors, such
as myo-inositol, 1L-Ins-1-P and 1D-Ins-1-P. The results have demonstrated the
strict substrate selectivity of CdMshA. Furthermore, its reaction kinetics with
UDP-GlcNAc and 1L-Ins-1-P as substrates were characterized, while site-directed
mutagenesis of CdMshA disclosed that its amino acid residues N28, K81 and R157
were essential for its enzymatic activity.
PMID- 28406518
TI - A multicomponent macrocyclization strategy to natural product-like cyclic
lipopeptides: synthesis and anticancer evaluation of surfactin and mycosubtilin
analogues.
AB - A multicomponent macrocyclization strategy towards cyclic lipopeptides is
described. The approach relies on the utilization of the Ugi and Passerini
multicomponent reactions for the cyclization of peptides and oxo-peptides, and
here it is employed for the construction of a small library of analogues of the
natural products mycosubtilin and surfactin A. A key feature of this method is
the simultaneous incorporation of either one or two exocyclic lipid tails along
with the macrocyclic ring closure, which is only possible due to the
multicomponent nature of the macrocyclization step. The evaluation of the
anticancer activity of the lipopeptide library showed that the installation of a
second lipid moiety in the surfactin scaffold leads to a more potent cytotoxicity
in cancer cells. This is a new example of the multicomponent reaction potential
in rapidly producing natural product analogues for biological screening.
PMID- 28406519
TI - syn-Selective crotylation of aldehydes using bismuth-crotyl bromide-(1-butyl-3
methylimidazolium bromide) combination: some synthetic applications.
AB - The Bi-[bmim][Br] combination has been found to offer high syn-selectivity in the
crotylation of aldehydes with crotyl bromide using practically stoichiometric
amounts of the reagents. The room temperature ionic liquid (RTIL), [bmim][Br],
activated Bi metal in the presence of oxygen to produce crotylbismuthdibromide,
which reacted with the aldehydes at room temperature. The major anti-syn
diastereomeric product obtained from the crotylation of (R)
cyclohexylideneglyceraldehyde was utilized for the synthesis of dictyostatin and
cryptophycin segments, and (+)-cis-aerangis lactone, using standard synthetic
protocols.
PMID- 28406520
TI - The folding mechanism and key metastable state identification of the PrP127-147
monomer studied by molecular dynamics simulations and Markov state model
analysis.
AB - The structural transition of prion proteins from a native alpha-helix (PrPC) to a
misfolded beta-sheet-rich conformation (PrPSc) is believed to be the main cause
of a number of prion diseases in humans and animals. Understanding the molecular
basis of misfolding and aggregation of prion proteins will be valuable for
unveiling the etiology of prion diseases. However, due to the limitation of
conventional experimental techniques and the heterogeneous property of oligomers,
little is known about the molecular architecture of misfolded PrPSc and the
mechanism of structural transition from PrPC to PrPSc. The prion fragment 127-147
(PrP127-147) has been reported to be a critical region for PrPSc formation in
Gerstmann-Straussler-Scheinker (GSS) syndrome and thus has been used as a model
for the study of prion aggregation. In the present study, we employ molecular
dynamics (MD) simulation techniques to study the conformational change of this
fragment that could be relevant to the PrPC-PrPSc transition. Employing extensive
replica exchange molecular dynamics (REMD) and conventional MD simulations, we
sample a huge number of conformations of PrP127-147. Using the Markov state model
(MSM), we identify the metastable conformational states of this fragment and the
kinetic network of transitions between the states. The resulting MSM reveals that
disordered random-coiled conformations are the dominant structures. A key
metastable folded state with typical extended beta-sheet structures is identified
with Pro137 being located in a turn region, consistent with a previous
experimental report. Conformational analysis reveals that intrapeptide
hydrophobic interaction and two key residue interactions, including Arg136-His140
and Pro137-His140, contribute a lot to the formation of ordered extended beta
sheet states. However, network pathway analysis from the most populated
disordered state indicates that the formation of extended beta-sheet states is
quite slow (at the millisecond level), as large structural rearrangement is
needed from disordered states. We speculate that the formation process of the
extended beta-sheet folded states may represent an important event during the
early formation of prion oligomers and the results of our study provide insights
into the molecular details of the early stage of prion aggregation.
PMID- 28406521
TI - Dissection of the neocarazostatin: a C4 alkyl side chain biosynthesis by in vitro
reconstitution.
AB - Neocarazostatin A (1) is a potent free radical scavenger possessing an intriguing
tricyclic carbazole nucleus with a C4 alkyl side chain attached to ring "A".
Although the biosynthetic gene cluster of 1 (nzs) has been identified, and
several key steps of the pathway have been well characterized, the enzyme(s)
involved in the biosynthesis of the C4 unit still remains obscure. In this work,
we demonstrate that three enzymes, including one (MA37-FabG) from primary fatty
acid metabolism and two pathway-specific ones (NzsE and NzsF), are responsible
for the formation of the side chain precursor. We show that NzsE is a free
standing acyl carrier protein (ACP), and NzsF, which is a homolog of beta
ketoacyl-acyl carrier protein synthase III (KAS III, also called FabH), catalyzes
a decarboxylative condensation between an acetyl-CoA and the NzsE bound malonyl
thioester to generate acetoacetyl-NzsE. We also show that NzsF can only accept
NzsE as its cognate ACP substrate, suggesting that NzsE and NzsF constitute
pathway-specific KAS III enzyme pairs for the assembly line of 1. Furthermore, we
have identified two FabG (the NADPH-dependent reductase) homologs from the fatty
acid biosynthesis pathway that can reduce the 3-keto group of acetoacetyl-NzsE to
generate a 3-hydroxybutyl-NzsE product, which is the putative intermediate for
the following incorporation into 1. Therefore, our work successfully
reconstitutes the biosynthetic pathway of the C4 alkyl side chain of 1in vitro,
and sheds light on the potential of engineering NzsE/F for producing novel
neocarazostatin analogues in the host strain.
PMID- 28406522
TI - Inhibition of polyglutamine aggregation by SIMILAR huntingtin N-terminal
sequences: Prospective molecules for preclinical evaluation in Huntington's
disease.
AB - The mutant huntingtin protein (mHtt) fragments with expanded polyglutamine
sequence forms microscopically visible aggregates in neurons, a hallmark of
Huntington's disease (HD). The aggregation process and aggregates are possible
targets of therapeutic intervention in HD. Owing to the lack of treatment and
cure, the patients die within 15-20 years after the disease onset. Therefore,
discovering therapeutic molecules that may either inhibit the aggregation
mechanism or downregulate the toxic effects of mHtt are highly needed. This study
demonstrates the design and use of peptide inhibitors based on the role played by
the N-terminal seventeen amino acid sequence (NT17 ) of huntingtin fragment in
its aggregation. Fug-NT17 (Fugu), Xen-NT17 (Xenopus), Dro-NT17 (Drosophila), Aib
NT17 , and Pro-NT17 sequences were tested for their ability to inhibit
aggregation. Among them, the first three are the sequence variants of human NT17
from evolutionarily distant organisms and the latter two are the analogs of human
NT17 -containing aminoisobutyric acid (Aib) and proline (Pro). Four out of five
inhibited the aggregation of huntingtin fragment, NT17 Q35 P10 K2 polypeptide.
Data indicate that the physicochemical properties of the inhibitors play a
crucial role in exhibiting the inhibitory effect. These inhibitors can be tested
in cell and animal models for the preclinical evaluation in the treating of HD.
PMID- 28406524
TI - Androgen receptor-positive, triple-negative breast cancer.
PMID- 28406523
TI - Exposure to extrinsic stressors, social defeat or bisphenol A, eliminates sex
differences in DNA methyltransferase expression in the amygdala.
AB - Chemical and psychological stressors can exert long lasting changes in brain
function and behaviour. Changes in DNA methylation have been shown to be an
important mechanism mediating long lasting changes in neural function and
behaviour, especially for anxiety-like or stress responses. In the present study,
we examined the effects of either a social or chemical stressor on DNA
methyltransferase (DNMT) gene expression in the amygdala, an important brain
region modulating stress responses and anxiety. In adult California mice
(Peromyscus californicus) that were naive to social defeat, females had higher
levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than
males. In addition, mice that underwent social defeat stress showed reduced Dnmt1
and Dnmt3a expression in the CeA of females but not males. A second study using
more anatomically specific punch samples replicated these effects for Dnmt1.
Perinatal exposure (spanning from periconception through lactation) to bisphenol
A or ethinyl oestradiol (oestrogens in birth control pills) also abolished sex
differences in Dnmt1 expression in the CeA but not the basolateral amygdala.
These findings identify a robust sex difference in Dnmt1 expression in the CeA
that is sensitive to both psychological and chemical stressors. Future studies
should aim to examine the impact of psychological and chemical stressors on DNA
methylation in the CeA and also investigate whether Dnmt1 may have an
underappreciated role in plasticity in behaviour.
PMID- 28406525
TI - An improved radiosynthesis of O-(2-[18 F]fluoroethyl)-O-(p
nitrophenyl)methylphosphonate: A first-in-class cholinesterase PET tracer.
AB - O-(2-Fluoroethyl)-O-(p-nitrophenyl) methylphosphonate 1 is an organophosphate
cholinesterase inhibitor that creates a phosphonyl-serine covalent adduct at the
enzyme active site blocking cholinesterase activity in vivo. The corresponding
radiolabeled O-(2-[18 F]fluoroethyl)-O-(p-nitrophenyl) methylphosphonate, [18
F]1, has been previously prepared and found to be an excellent positron emission
tomography imaging tracer for assessment of cholinesterases in live brain,
peripheral tissues, and blood. However, the previously reported [18 F]1 tracer
synthesis was slow even with microwave acceleration, required high-performance
liquid chromatography separation of the tracer from impurities, and gave less
optimal radiochemical yields. In this paper, we report a new synthetic approach
to circumvent these shortcomings that is reliant on the facile reactivity of bis
(O,O-p-nitrophenyl) methylphosphonate, 2, with 2-fluoroethanol in the presence of
DBU. The cold synthesis was successfully translated to provide a more robust
radiosynthesis. Using this new strategy, the desired tracer, [18 F]1, was
obtained in a non-decay-corrected radiochemical yield of 8 +/- 2% (n = 7) in >99%
radiochemical and >95% chemical purity with a specific activity of 3174 +/- 345
Ci/mmol (EOS). This new facile radiosynthesis routinely affords highly pure
quantities of [18 F]1, which will further enable tracer development of OP
cholinesterase inhibitors and their evaluation in vivo.
PMID- 28406526
TI - Changes in the nutritional quality of five Mangifera species harvested at two
maturity stages.
AB - BACKGROUND: There are 69 species of edible Mangifera recognized in Southeast
Asia. Most of these species have not been characterized for nutritional
properties. This paper describes the nutritional quality of the pulp of several
Mangifera species - Mangifera casturi, Mangifera lalijiwa, Mangifera odorata,
Mangifera zeylanica and two cultivars of Mangifera indica, 'Tommy-Kent' and
'Tommy Atkins' - at two maturity stages. RESULTS: The results showed that
nutritional quality varied with maturity stage and among species. The immature
pulp of all species had higher content of total dietary fibre, vitamin C, vitamin
E, total soluble polyphenols and antioxidant capacity. In mature pulp, the
protein, ash, fat, soluble carbohydrate and B vitamin values were higher in all
species. The species with the best nutritional quality were, in order from
highest to lowest, M. casturi, M. odorata, M. zeylanica, M. indica cultivars and
M. lalijiwa. CONCLUSION: The fruit pulp of three species had higher nutritional
quality at both maturity stages in comparison with M. indica cultivars. These
other Mangifera species can be nutritionally important in communities facing food
insecurity and have potential as emerging crops. The decline of these valuable
species in their natural habitats is an increasing concern, and their nutritional
properties justify greater efforts to protect them. (c) 2017 Society of Chemical
Industry.
PMID- 28406527
TI - Modified weekly regimen of cisplatin, epirubicin and paclitaxel induced a durable
response in two cases of metastatic extramammary Paget's disease.
AB - Metastatic extramammary Paget's disease (EMPD) is a rare cancer with no
standardized treatment. We report two cases of metastatic EMPD treated with a
modified weekly PET (cisplatin, epirubicin and paclitaxel) regimen given biweekly
(i.e. 2 weeks on/2 weeks off) that had durable responses. Case 1 was a 74-year
old man with EMPD metastatic to lymph nodes, lung, and bone who presented with a
hemorrhagic tumor on the scrotum. We tried the PET regimen weekly, but adjusted
the interval to biweekly after two doses because of hematological side-effects.
After five doses, he showed a partial response (PR) on imaging, including the
bone lesions. The lesions have remained the same size for 1 year. Case 2 was a 65
year-old man with EMPD metastatic to a right inguinal lymph node who presented
with an erosive tumor on the scrotum. He was started on weekly docetaxel.
However, the lymph node grew and iliac lymph node metastasis developed.
Therefore, we tried the PET regimen with a 2 weeks on/2 weeks off schedule. After
five doses, he showed a PR. In both cases, all adverse effects were manageable
and this modified regimen could be administrated on an outpatient basis. With no
current validated chemotherapy regimen, clinicians may consider a modified weekly
PET regimen in future treatment of metastatic EMPD.
PMID- 28406528
TI - Localized cutaneous immunoglobulin light chain kappa-positive amyloidosis
associated with juvenile dermatomyositis.
PMID- 28406529
TI - Validation of the BioPRYN enzyme-linked immunosorbent assay for detection of
pregnancy-specific protein-B (PSPB) and diagnosis of pregnancy in American bison
(Bison bison).
AB - This study assessed the accuracy of the commercial BioPRYN(r) ELISA for the
detection of pregnancy-specific protein-B (PSPB) using a single blood sample to
determine pregnancy status in American bison (Bison bison). A total of 49 bison
cows were used in the study, and sampled at two time-points during the gestation
period, fall and spring, correlating with early- to mid-term gestation (average
62.9 days post-mating) and mid- to late-term gestation (average 229.2 days post
mating), respectively. Sensitivity of the test during early- to mid-term
gestation sampling period (fall) was 87.1%, while specificity was 100%;
sensitivity of the test during late-term gestation sampling period (spring) was
96.3%, while specificity remained at 100%. In total, the test showed a total
sensitivity of 91.4%, specificity of 100% and total accuracy of 93.8%, similar to
domestic cattle. Use of the single-sample BioPRYN(r) ELISA in American Bison for
pregnancy diagnosis is economical and practical, minimizing animal handling time,
frequency and subsequent stress while providing accurate results for pregnancy
diagnosis at 62 days post-mating. This method should be considered over more
traditional pregnancy diagnosis methods for use in managed bison herds.
PMID- 28406530
TI - Pseudoepitheliomatous keratotic and micaceous balanitis treated with topical 5
fluorouracil and liquid nitrogen.
AB - Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an uncommon
premalignant condition involving the glans penis. We report the case of an 86
year-old man who presented with phimosis and pain on retracting his foreskin. He
had previously undergone circumcision, which revealed a hyperkeratotic plaque
with thin mica-like scales involving his glans penis. Histology of the lesion
showed hyperkeratosis, parakeratosis, epidermal acanthosis and papillomatosis
with no evidence of dysplasia. Immunohistochemistry for human papillomavirus was
negative. The patient was treated with topical 5-fluorouracil and liquid nitrogen
with clinical improvement. He is now under long-term surveillance for verrucous
carcinoma and squamous cell carcinoma.
PMID- 28406531
TI - Economic burden of psoriatic patients in Japan: Analysis from a single outpatient
clinic.
AB - Topical and systemic agents have dramatically improved the treatment efficacy of
psoriasis. Few reports, however, exist describing the economic burden in Japanese
psoriatic patients. The aim of the study was to evaluate the total costs as well
as cost versus efficacy of topical and systemic treatments of psoriatic patients
under the Japanese health insurance system. The retrospective study was performed
from the database of our clinic, which is located in Hokkaido Prefecture. Cost
and effectiveness of psoriatic patients were evaluated during the 12-month period
from April 2015 to March 2016. Data were collected and calculated for the total
cost per year, treatment efficacy and cost versus efficacy. The mean total cost
of topical corticosteroid treatment was Y18 184/year and was lowest among the
treatments. The systemic treatment with biologics was most expensive and the
costs were over Y400 000/year. Among the topical treatments,
calcipotriol/betamethasone dipropionate was most expensive (Y34 693/year).
However, cost versus efficacy was not significantly different from that of
topical corticosteroid treatments. The cost of secukinumab was highest among all
the treatments (Y631 600/year). However, treatment day per cost was lowest of all
the psoriasis treatments. Biologics showed the highest cost than topical or
systemic treatments. However, they showed most marked efficacy in terms of
improving the psoriatic skin lesions.
PMID- 28406533
TI - Novel heterozygous mutation, c.74C>G (p.Pro25Arg), in the U2HR gene underlies
Marie Unna hereditary hypotrichosis in a Japanese family.
PMID- 28406532
TI - Endometrial gene expression in primiparous dairy cows at the end of the voluntary
waiting period is affected by nutrition: Total mixed ration vs increasing levels
of herbage allowance.
AB - The study postulated that differential nutritional management during the early
lactation period would be reflected in endometrial expression of genes related to
embryo growth at the end of the voluntary waiting period. Thus, the effect of the
combined use of total mixed ration (TMR) and grazing under different herbage
allowances during the first 75 days post-partum (DPP) on endometrial gene
expression was evaluated in primiparous dairy cows. Cows were blocked by body
weight, age and body condition score and randomly assigned to three grazing
treatments: high (HA, 30 kg DM per cow per day), medium (MA, 15 kg DM per cow per
day) and low (LA, 7.5 kg DM per cow per day) herbage allowance (mixed pasture,
2,600 kg DM per ha) plus 8 kg DM of supplement or TMR (55% forage, 45%
concentrate) fed ad libitum (TMR) from calving to 75 DPP. At 57 DPP, cows were
synchronized for oestrus (day 0, 68 DPP) and at day 7, endometrial biopsies were
obtained. The nutritional treatment did not affect insulin, IGF-1 and leptin
concentrations on days 0, 4 or 7. Expression of IGF1, IGFBP3, IGFBP4, ADIPOR1 and
ADIPOR2 mRNA was significantly affected by the nutritional treatment. Endometrial
IGF1 and IGFBP4 mRNA were twofold greater in TMR and HA than MA and LA cows.
Expression of IGFBP3 and ADIPOR1 mRNAs was greater in TMR and HA than MA cows,
but did not differ from LA cows. All groups had greater expression of ADIPOR2
mRNA than MA cows. This study provided solid evidence of the importance of
nutritional management during early lactation on uterine environment at the end
of the voluntary waiting period. The greater expression of genes related to
embryo growth and uterine function (IGF system, progesterone and adiponectin
receptors) in cows fed diets maximizing energy intake suggests a favourable
environment for embryonic growth, which may explain the improved reproductive
performance of cows in good energy balance.
PMID- 28406534
TI - Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein levels and
liver fibrosis: A meta-analysis.
AB - BACKGROUND AND AIM: A reliable, non-invasive biomarker for diagnosis of liver
fibrosis in chronic liver disease patients is needed. The aim of this study was
to assess by meta-analysis the efficacy of measuring serum levels of Wisteria
floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP), a novel and
promising biomarker, for staging liver fibrosis and predicting the development of
hepatocellular carcinoma and overall survival. METHODS: We performed a meta
analysis using online journal database searches. We identified 39 studies, 21 of
which met the criteria for meta-analysis. Sensitivity and specificity of WFA+
M2BP for assessing liver fibrosis staging in chronic liver diseases with broad
etiologies were determined. Hazard ratios with 95% confidence intervals were also
used for predicting hepatocellular carcinoma development and overall survival.
RESULTS: With WFA+ -M2BP, the sensitivity and specificity for predicting
significant fibrosis (>= F2), advanced fibrosis (>= F3), and liver cirrhosis (=
F4) were 0.690 and 0.778, 0.764 and 0.758, and 0.818 and 0.839, respectively.
Sensitivity and specificity for diagnosing liver fibrosis in patients with
hepatitis C virus were mostly higher than those in overall patients. However,
sensitivity and specificity for diagnosing liver fibrosis in patients with
hepatitis B virus were lower than those in overall patients. Overall, hazard
ratios for development of hepatocellular carcinoma and overall survival were
5.946 and 1.068, respectively. CONCLUSIONS: These results suggest that serum WFA+
-M2BP is a reliable predictor for liver fibrosis staging and a good substitute
for liver biopsy. It is also useful for predicting both hepatocellular carcinoma
development and overall survival.
PMID- 28406535
TI - Burgess iridium(I)-catalyst for selective hydrogen isotope exchange.
AB - We have evaluated the commercially available Burgess catalyst in hydrogen isotope
exchange reactions with several substrates bearing different directing group
functionalities and have obtained moderate to high (50%-97%D) deuterium
incorporations. The broad applicability in hydrogen isotope exchange reactions
makes the Burgess catalyst a possible alternative compared to other commercially
available iridium(I)-catalysts.
PMID- 28406536
TI - Solitary angiokeratoma presenting as cutaneous horn.
PMID- 28406537
TI - Non-invasive prenatal screening versus prenatal diagnosis by array comparative
genomic hybridization: a comparative retrospective study.
AB - OBJECTIVE: To calculate the proportion of array comparative genomic hybridization
(aCGH) pathogenic results, that would not be detectable by non-invasive prenatal
screening (NIPS). METHODS: This is a comparative study using data from 2779
fetuses, which underwent invasive prenatal diagnosis, and the samples were
analyzed using aCGH. The simulated NIPS assay would test for trisomies 21, 18,
13, monosomy X, 47, XXX, 47, XYY, and 47, XXY. Indications for invasive testing
were grouped into categories and the absolute, relative rates of
pathogenic/likely pathogenic results of aCGH analysis that would not be
detectable by NIPS were calculated. RESULTS: The expected rate of aCGH-detected
abnormalities that would not be detectable by NIPS was 28.0% (95% CI 14.3-47.6)
for nuchal translucency (NT) 95 to 99th centile; 14.3% (95% 5.0-34.6) for NT >
99th centile; 34.2% (95% CI 21.1-50.1) for high-risk first-trimester results
(regardless of NT); 52.4% (95% CI 32.4-71.7) for second-trimester markers; and
50.0% (95% CI 26.8-73.2) for advanced maternal age. The overall rate of aCGH
pathogenic/likely pathogenic results was 5.0% and 44.0% (95% CI 36.0-52.2) of
them would not be detected by NIPS. CONCLUSIONS: Approximately half of the
abnormal aCGH results would not be detectable by standard NIPS assays,
highlighting the necessity of pre-test counseling, and illustrating the
limitations of NIPS. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28406538
TI - Acetylcholine modulates gamma frequency oscillations in the hippocampus by
activation of muscarinic M1 receptors.
AB - Modulation of gamma oscillations is important for the processing of information
and the disruption of gamma oscillations is a prominent feature of schizophrenia
and Alzheimer's disease. Gamma oscillations are generated by the interaction of
excitatory and inhibitory neurons where their precise frequency and amplitude are
controlled by the balance of excitation and inhibition. Acetylcholine enhances
the intrinsic excitability of pyramidal neurons and suppresses both excitatory
and inhibitory synaptic transmission, but the net modulatory effect on gamma
oscillations is not known. Here, we find that the power, but not frequency, of
optogenetically induced gamma oscillations in the CA3 region of mouse hippocampal
slices is enhanced by low concentrations of the broad-spectrum cholinergic
agonist carbachol but reduced at higher concentrations. This bidirectional
modulation of gamma oscillations is replicated within a mathematical model by
neuronal depolarisation, but not by reducing synaptic conductances, mimicking the
effects of muscarinic M1 receptor activation. The predicted role for M1 receptors
was supported experimentally; bidirectional modulation of gamma oscillations by
acetylcholine was replicated by a selective M1 receptor agonist and prevented by
genetic deletion of M1 receptors. These results reveal that acetylcholine release
in CA3 of the hippocampus modulates gamma oscillation power but not frequency in
a bidirectional and dose-dependent manner by acting primarily through muscarinic
M1 receptors.
PMID- 28406540
TI - Salivary chromogranin A levels correlate with disease severity but do not reflect
anxiety or personality of adult patients with atopic dermatitis.
AB - Stress-induced scratching is an issue in patients with adult atopic dermatitis
(AD). Although itching and stress are believed to be intimately related, no
objective index is available; therefore, most evaluations are subjective. Using
saliva, which is easily collected, we investigated the degree to which AD
severity and patient stress levels are reflected in stress proteins in the
saliva. Here, we evaluated the severity (Scoring Atopic Dermatitis [SCORAD]
score), stress (State-Trait Anxiety Index [STAI] score), personality (Tokyo
University Egogram [TEG] II score) and quality of life (Dermatology Life Quality
Index [DLQI] score) of 51 patients with AD who were examined in the Department of
Dermatology of Shimane University between April and December 2015. We collected
saliva and measured salivary chromogranin A (CgA), amylase and cortisol. The
amount of salivary CgA per protein in patients with AD was correlated with their
SCORAD score (r = 0.458, P < 0.001). There was no correlation between cortisol or
amylase levels and SCORAD score. SCORAD score was correlated with DLQI (r =
0.390, P = 0.006). CgA per protein was correlated with DLQI (r = 0.393, P =
0.004). There was no correlation between scores for the anxiety component of the
STAI, TEG II or DLQI. Our results suggested that patients with more severe AD may
have high stress levels. The personalities of these patients with AD tended to
involve elevated anxiety levels.
PMID- 28406539
TI - Mechanisms of drug-drug interaction between rifampicin and fusidic acid.
PMID- 28406541
TI - Stereoselective and Enantiospecific Mono- and Bis-C-H Azidation of Troger Bases:
Insight on Bridgehead Iminium Intermediates and Application to Anion-Binding
Catalysis.
AB - In the context of Troger base chemistry, regio- and stereoselective Csp3 -H
azidation reactions are reported. Azide functional groups are introduced at
either one or the two benzylic positions selectively. Mild conditions and good
yields are afforded by the combination of TMSN3 and iodosobenzene PhIO. The
process occurs with high enantiospecificity (es 96-99 %) and-interestingly and
importantly-via bridgehead iminium intermediates as shown by mechanistic and in
silico studies. Finally, mono- and bistriazole derivatives were prepared in high
yields and enantiospecificity by using copper-catalyzed alkyne azide
cycloaddition (CuAAC) reactions; some of the products were used as anion-binding
organocatalysts for the tritylation of amines and alcohols.
PMID- 28406542
TI - Physiological gases in health and disease - key regulatory factors, not just a
lot of hot air.
PMID- 28406543
TI - Reflecting on a year of change and the year ahead.
PMID- 28406544
TI - Halogen-Free Synthesis of Carbamates from CO2 and Amines Using Titanium
Alkoxides.
AB - A direct synthesis of carbamates from amines and carbon dioxide in the presence
of Ti(OR)4 (R=nBu (1), Me (2), Et (3), nPr (4)) was investigated. Aniline was
reacted with titanium n-butoxide (1) in the presence of carbon dioxide (5 MPa) to
give the corresponding n-butyl N-phenylcarbamate (BPC) in nearly quantitative
yield (99 %) within 20 min. Furthermore, 1 could be regenerated upon reaction
with n-butanol during water removal. The recovered 1 could then be reused in a
subsequent reaction.
PMID- 28406545
TI - Diagnosing nocturnal paroxysmal hemoglobinuria: a single-center 4-year
experience.
AB - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease and can
present as a wide range of signs and symptoms. As such, the indication for
diagnostic testing for PNH is not always straightforward. Therefore, we analyzed
all first-time samples tested over a 56-month period to determine the clinical
settings with a high probability of detecting a PNH clone. METHODS: We
retrospectively analyzed 323 first-time PNH flow cytometry tests, including LDH,
cytopenias, direct antiglobulin test (DAT), and clinical indication for testing
as available at the time of testing. RESULTS: The probability of finding a PNH
clone was 47% in patients tested because of aplastic/hypoplastic bone marrow
disorders, 10% in DAT-negative hemolytic anemia (HA), 5% in myelodysplastic
syndromes (MDS), 3% in cytopenias other than HA, and 2% in thrombosis. When
testing for another reason than the indications described before, there were no
positive samples. CONCLUSION: Our findings reinforce guidelines from the
International PNH Interest Group which suggest testing for PNH in the setting of
unusual thrombosis, HA, aplastic/hypoplastic bone marrow disorders, or MDS, as
these have a higher pretest probability. This probability drops to zero in our
study in nonrecommended indications. This reflects the need for better education
of clinicians about the disease PNH and the indications for diagnostic testing.
PMID- 28406546
TI - Role of hepatic resection in patients with intermediate-stage hepatocellular
carcinoma: A multicenter study from Japan.
AB - Transarterial chemoembolization (TACE) is recommended for patients with
intermediate-stage (Barcelona Clinic Liver Cancer criteria B [BCLC-B])
hepatocellular carcinoma (HCC). However, patients with BCLC-B HCC can differ in
background factors related to hepatic function, as well as tumor size and number.
In the present study, we clarified the role of hepatic resection in patients with
BCLC-B HCC. A total of 489 BCLC-B HCC patients with Child-Pugh class A disease
initially treated with hepatic resection or TACE were included. After propensity
score matching (n = 264), hepatic resection (hazard ratio [HR], 0.56; 95%
confidence interval [CI], 0.35-0.91) was independently associated with survival
in the multivariate analysis. We then divided patients into two groups based on
the results of statistical analysis. There were 170 patients treated with
resection and 319 with TACE. Child-Pugh score and number of tumors (cut-off,
three tumors) were independently associated with type of HCC treatment in the
multivariate analysis. We then divided patients in Group A (Child-Pugh score of 5
and <=3 tumors; n = 186) and Group B (Child-Pugh score of 6 or >=4 tumors; n =
303). In Group A, cumulative survival was significantly higher in the hepatic
resection group than in the TACE group (P = 0.014). In Cox proportional hazards
models, hepatic resection (HR, 0.38; 95% CI, 0.23-0.64) was independently
associated with survival in Group A patients. In Group B, treatment status was
not associated with overall survival. Hepatic resection should be considered in
patients with a Child-Pugh score of 5 and <=3 tumors, despite having BCLC-B HCC.
PMID- 28406547
TI - Factors affecting smartphone adoption for accessing information in medical
settings.
AB - OBJECTIVES: This study aimed to acquire knowledge about the factors affecting
smartphone adoption for accessing information in medical settings in Iranian
Hospitals. METHODS: A qualitative and quantitative approach was used to conduct
this study. Semi-structured interviews were conducted with 21 medical residents
and interns in 2013 to identify determinant factors for smartphone adoption.
Afterwards, nine relationships were hypothesised. We developed a questionnaire to
test these hypotheses and to evaluate the importance of each factor. Structural
equation modelling was used to analyse the causal relations between model
parameters and to accurately identify determinant factors. RESULTS: Eight factors
were identified in the qualitative phase of the study, including perceived
usefulness, perceived ease of use, training, internal environment, personal
experience, social impacts, observability and job related characteristics. Among
the studied factors, perceived usefulness, personal experience and job related
characteristics were significantly associated with attitude to use a smartphone
which accounted for 64% of the variance in attitude. Perceived usefulness had the
strongest impact on attitude to use a smartphone. CONCLUSION: The factors that
emerged from interviews were consistent with the Technology Acceptance Model
(TAM) and some previous studies. TAM is a reliable model for understanding the
factors of smartphone acceptance in medical settings.
PMID- 28406548
TI - Dentists' use of validated child dental anxiety measures in clinical practice: a
mixed methods study.
AB - BACKGROUND: Assessing anxiety is an important part of the assessment of a child
presenting for dental treatment; however, the use of dental anxiety scales in
practice is not well-documented. AIMS: To introduce child dental anxiety scales,
and to monitor the extent to which dentists used them; to explore the experience
and views of dentists regarding anxiety assessment. DESIGN: A mixed-methods
design was employed. METHOD: A protocol for child anxiety assessment was
introduced to paediatric dentists in Eastman Dental Hospital. After 6 months, 100
patient files were audited to examine compliance with the protocol. Fourteen
dentists were interviewed to explore their experience and views regarding anxiety
assessment. RESULTS: Only five patients were assessed using the scales. Thematic
analysis of the dentist interviews revealed three themes: 'Clinical observations
and experience: The gold standard'; 'Scales as an estimate or adjunct'; and
'Shortcomings and barriers to using scales'. CONCLUSIONS: The dentists in our
study did not use anxiety scales, instead they rely on their own
experience/judgement. Therefore, scales should be recommended as an adjunct to
judgement. Brief scales are recommended as clinicians lack time and expertise in
administering anxiety questionnaires. Advantages of using scales and hands-on
experience could be incorporated more in undergraduate training.
PMID- 28406549
TI - Postoperative ileus, a diagnosis by exclusion? Comment on relation between
postoperative ileus and anastomotic leakage after colorectal resection: a post
hoc analysis of a prospective randomized controlled trial.
PMID- 28406550
TI - Unusual Assembly and Conversion of Graphene Quantum Dots into Crystalline
Graphite Nanocapsules.
AB - The development of a facile strategy for conversion of graphene quantum dots
(GQDs) into crystalline graphite is of great practical significance and still
remains challenging. Herein, rationally assembled crystalline-intercrossed
graphite nanocapsules (CI-GNCs) have been realized by a one-step
electrochemically induced strategy with the assistance of a soft template, in
which the GQDs act as the initial building blocks. The as-prepared CI-GNCs
exhibit highly crystalline graphitic nanostructures. Moreover, they possess
promising electrocatalytic activity for the oxygen reaction reduction (ORR) in
alkaline medium. This simple fabrication technology presents a great advance for
synthesizing CI-GNCs composite catalysts, which have potential as new metal-free
catalysts for efficient ORR applications.
PMID- 28406551
TI - Preparation of Magnetically Recyclable Yolk/Shell Fex Oy /PdPt@CeO2 Nanoreactors
with Enhanced Catalytic Activity.
AB - Noble metal nanoparticles (NPs) have recently received considerable attention
from researchers working in the field of catalysis. However, the development of
new methods allowing these materials to reach their maximum catalytic properties
remains challenging. Nanoreactors could lead to dramatic improvements in activity
with the help of the intrinsic confinement effect. In this study, we designed a
series of yolk/shell Fex Oy /PdPt@CeO2 composites, where the Fex Oy NPs acted as
a movable core, allowing for the uniform distribution of the PdPt alloys on the
inner surface of the CeO2 shell. The high porosity and existence of hollow voids
in the CeO2 shell allowed these Fex Oy /PdPt@CeO2 composites to be used as
nanoreactors in catalytic reactions. As well this confinement effect, we
identified two structural features that led to enhanced catalytic activity,
including (i) the replacement of monometallic NPs with a bimetallic PdPt alloy
and (ii) the replacement of a chemically inert support with a reactive CeO2
shell. The resulting nanoassembled catalysts displayed higher activities toward
the catalytic reduction of dyes than the reference samples. Moreover, these
catalysts were readily recovered and reused because of the magnetic Fex Oy core.
PMID- 28406552
TI - Auckland regional emergency medicine trainee mentoring uptake survey.
AB - OBJECTIVE: The primary objective of this study is to quantify how many Auckland
region emergency medicine (EM) trainees would like a formal mentoring programme.
The secondary objectives were to quantify how many Auckland region EM trainees
would like to participate in a formal mentoring programme; to determine trainees'
current understanding of mentoring; how trainees prefer mentors to be allocated;
why trainees may want a mentor; what mentees perceive would be good qualities in
a mentor; and trainees' prior experience with mentoring. METHODS: Online survey
of EM trainees in the Auckland region in June 2015. RESULTS: Of 61 potential
respondents, 40 (65.6%) respondents replied to the survey. Of the 40, 38 (95%;
95% confidence interval (CI) 82.6-99.5) respondents indicated they would like
some form of mentoring system, and of the 38, 25 (65.8%; 95% CI 49.8-78.9)
preferred this to be formal. Of the 38, 19 (50%; 95% CI 34.9-65.2) currently
wanted assistance obtaining a mentor. Of the 40, 30 (75%; 95% CI 59.6-86.0) are
not currently in any form of mentoring relationship. Respondents believed that
mentors would be most beneficial in critical incidents, career development and
with work/life balance. The attributes participants considered most important in
a mentor were respecting confidentiality, being honest and the ability to provide
constructive feedback. CONCLUSIONS: Many EM trainees in Auckland want a formal
mentoring system and would like a mentor. Appropriate mentor-mentee matching
through a formalised voluntary system, with adequate mentor training, may enable
the Auckland region to develop a suitable mentoring programme for EM trainees.
PMID- 28406553
TI - Detection of Factor XIII deficiency: data from multicentre exercises amongst UK
NEQAS and PRO-RBDD project laboratories.
AB - INTRODUCTION: FXIII deficiency is a rare bleeding disorders, and specific FXIII
assays are recommended to detect this deficiency. We investigated the performance
and accuracy of FXIII investigations in two exercises, comparing centres enrolled
in the PRO-RBDD project (prospective data collection on patients with fibrinogen
and Factor XIII deficiencies), and UK NEQAS BC centres. METHODS: Samples from a
FXIII deficient subject and a normal donor were sent to participating centres, to
investigate for FXIII deficiency, and interpret their results. Median,
coefficient of variation and range were determined. RESULTS: Results were
returned from 98 UK NEQAS BC and 28 PRO-RBDD centres. Up to 40% of UK NEQAS BC
and 52% of PRO-RBDD centres reported clot solubility results - with diagnostic
errors by two NEQAS BC centres (false negatives for the FXIII deficient sample)
and one PRO-RBDD centre (false positive for the normal sample). Over 70% of UK
NEQAS BC centres and PRO-RBDD centres performed FXIII assays. Median results were
similar between the two groups, with the exception of sample 3 in survey 2 (5.5
vs. 14.0 MU/dl for UK NEQAS BC and PRO-RBDD centres respectively, P < 0.001).
Diagnostic errors were made by 2 UK NEQAS BC centres. CONCLUSION: Approximately
70% of centres now employ FXIII assays, complying with international
recommendations. However, solubility tests continue to be used. Our data show
this can be successful, depending on the sensitivity of the method in use.
Diagnostic errors are made by centres using both solubility screens and FXIII
assays, and laboratories should ensure good quality assurance procedures to
improve diagnostic accuracy.
PMID- 28406554
TI - Vitamin D receptor gene polymorphisms association with the risk of sepsis and
mortality.
AB - Association of vitamin D receptor (VDR) gene polymorphisms with sepsis risk and
mortality was studied. VDR FokI CC genotype was associated with increased sepsis
risk (OR = 13.396, p = .000009) compared to the TT genotype. Results suggest
possible role of VDR FokI (rs2228570) as a molecular biomarker of increased
sepsis risk.
PMID- 28406556
TI - How We Came to Be: Evidence from Primate Relatives and Fossil Ancestors Offer
Clues to How Human Capabilities for Birth, Posture, and Walking Evolved.
PMID- 28406557
TI - Determinants of Iliac Blade Orientation in Anthropoid Primates.
AB - Orientation of the iliac blades is a key feature that appears to distinguish
extant apes from monkeys. Iliac morphology is hypothesized to reflect variation
in thoracic shape that, in turn, reflects adaptations for shoulder and forearm
function in anthropoids. Iliac orientation is traditionally measured relative to
the acetabulum, whereas functional explanations pertain to its orientation
relative to the cardinal anatomical planes. We investigated iliac orientation
relative to a median plane using digital models of hipbones registered to
landmark data from articulated pelves. We fit planes to the iliac surfaces,
midline, and acetabulum, and investigated linear metrics that characterize
geometric relationships of the iliac margins. Our results demonstrate that extant
hominoid ilia are not rotated into a coronal plane from a more sagittal position
in basal apes and monkeys but that the apparent rotation is the result of
geometric changes within the ilia. The whole ilium and its gluteal surface are
more coronally oriented in apes, but apes and monkeys do not differ in
orientation of the iliac fossa. The angular differences in the whole blade and
gluteal surface primarily reflect a narrower iliac tuberosity set closer to the
midline in extant apes, reflecting a decrease in erector spinae muscle mass
associated with stiffening of the lumbar spine. Mediolateral breadth across the
ventral dorsal iliac spines is only slightly greater in extant apes than in
monkeys. These results demonstrate that spinal musculature and mobility have a
more significant effect on pelvic morphology than does shoulder orientation, as
had been previously hypothesized. Anat Rec, 300:810-827, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28406558
TI - Mechanical Constraints on the Hominin Pelvis and the "Obstetrical Dilemma".
AB - The "obstetrical dilemma" posits that increases in birth canal dimensions during
hominin evolution were constrained by mechanical factors associated with bipedal
gait. This model has recently been challenged, in part on the basis of
experimental data showing little association between pelvic and proximal femoral
dimensions and locomotor costs among human experimental subjects. However,
complete rejection of the model is premature, for two reasons: (1) it is
difficult to extrapolate experimental results to naturalistic conditions and the
much more varied body form and possibly locomotor style of early hominins.
Relative pelvic breadth and femoral neck length in both australopiths and early
Homo are at or beyond the limits observed among modern humans, and there is
evidence that australopiths may have used an altered form of bipedal gait. (2)
Other mechanical factors in addition to locomotor cost are important when
assessing pelvic and proximal femoral morphology. Increasing biacetabular breadth
increases the joint reaction force (JRF) on the femoral head. Increasing femoral
neck length may reduce hip JRF, but also increases stress and fracture risk in
the femoral neck. Increasing both biacetabular breadth and femoral neck length
also increases mediolateral bending stress in the proximal femoral shaft,
necessitating substantial buttressing of the diaphysis. Thus, there are
mechanical consequences beyond simply locomotor costs that must be considered
when evaluating variation in pelvic and femoral morphology among past and extant
hominins. Anat Rec, 300:946-955, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406559
TI - Measuring Lateral Iliac Flare by Different Methods Risks Obscuring Evolutionary
Changes in the Pelvis.
AB - The orientation and morphology of the hominin ilium is functionally important for
locomotion, yet no standard method exists for quantifying its lateral flare. This
lack of standardization stems from fossil preservation issues and morphological
differences between hominin species. Many techniques have been developed to
measure flare based on what is preserved on a single fossil, but this makes
comparisons between fossil species challenging. In some cases, methods developed
based on australopith morphology are not appropriate for measuring the morphology
in genus Homo. Lateral iliac flare is the angle between the iliac blade and the
sagittal plane, and it affects the function and efficiency of the lesser gluteal
muscles. Four different methods of quantifying lateral iliac flare are reviewed
here, and assessed based on how well they reflect lateral iliac flare. The data
show that these metrics measure different parts of the pelvis, none measures
lateral iliac flare relative to the sagittal plane, and they yield different
results for which fossil hominin is the most (or least) flared. This
inconsistency puts paleoanthropologists at risk of misinterpreting the functional
importance of lateral iliac flare in hominin evolution. I propose two paths
forward to improve our assessment of flare: first, a geometric morphometric
comparison of iliac blade variation would properly assess the full three
dimensions of the ilium; second, in hominin fossils that are not complete or
numerous enough to include in a geometric morphometric analysis, two-dimensional
measurements may still be used to assess functional differences in the ilium
provided the researcher does not claim that they measure lateral iliac flare.
Anat Rec, 300:956-963, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406555
TI - International Guillain-Barre Syndrome Outcome Study: protocol of a prospective
observational cohort study on clinical and biological predictors of disease
course and outcome in Guillain-Barre syndrome.
AB - Guillain-Barre syndrome (GBS) is an acute polyradiculoneuropathy with a highly
variable clinical presentation, course, and outcome. The factors that determine
the clinical variation of GBS are poorly understood which complicates the care
and treatment of individual patients. The protocol of the ongoing International
GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study
that aims to identify the clinical and biological determinants and predictors of
disease onset, subtype, course and outcome of GBS is presented here. Patients
fulfilling the diagnostic criteria for GBS, regardless of age, disease severity,
variant forms, or treatment, can participate if included within 2 weeks after
onset of weakness. Information about demography, preceding infections, clinical
features, diagnostic findings, treatment, course, and outcome is collected. In
addition, cerebrospinal fluid and serial blood samples for serum and DNA is
collected at standard time points. The original aim was to include at least 1,000
patients with a follow-up of 1-3 years. Data are collected via a web-based data
entry system and stored anonymously. IGOS started in May 2012 and by January 2017
included more than 1,400 participants from 143 active centers in 19 countries
across 5 continents. The IGOS data/biobank is available for research projects
conducted by expertise groups focusing on specific topics including epidemiology,
diagnostic criteria, clinimetrics, electrophysiology, antecedent events,
antibodies, genetics, prognostic modeling, treatment effects, and long-term
outcome of GBS. The IGOS will help to standardize the international collection of
data and biosamples for future research of GBS.
PMID- 28406560
TI - The Anatomical Record Marches on by Exploring Evolution in the Second Part of Our
Special Issue on the Human Pelvis.
PMID- 28406561
TI - Lower Ilium Evolution in Apes and Hominins.
AB - Elucidating the pelvic morphology of the Pan-Homo last common ancestor (LCA) is
crucial for understanding ape and human evolution. The pelvis of Ardipithecus
ramidus has been the basis of controversial interpretations of the LCA pelvis. In
particular, it was proposed that the lower ilium became elongate independently in
the orangutan and chimpanzee clades, making these taxa poor analogues for the
pelvis of the LCA. This study examines the variation in relative lower ilium
height between and within living and fossil hominoid species (and other
anthropoids), and models its evolution using available fossil hominoids as
calibration points. We find nuanced differences in relative lower ilium height
among living hominoids, particularly in regards to gorillas, which do not have
elongate lower ilia (because they are likely to represent the plesiomorphic
hominoid condition for this trait). We also show that differences in relative
lower ilium height among hominoid taxa are not readily explained by differences
in size between species. Our maximum likelihood ancestral state reconstructions
support inferences that chimpanzees (Pan troglodytes in particular) and
orangutans evolved their elongate lower ilia independently. We also find that the
predicted lower ilium height of the Pan-Homo LCA is shorter than all great apes
except gorillas. This study adds to a growing body of evidence that finds
different regions of the body show different evolutionary histories in different
hominoids, and underscores that the unique combinations of morphologies of each
modern and fossil hominoid species should be considered when reconstructing the
mosaic nature of the Pan-Homo LCA. Anat Rec, 300:828-844, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28406562
TI - Development of Pelvic Sexual Dimorphism in Hylobatids: Testing the Obstetric
Constraints Hypothesis.
AB - Pelvic sexual dimorphism in primates is typically seen as the result of female
specific adaptations to obstetric constraints, which arise from the tight fit
between the neonate head and the maternal pelvis. However, it remains debated to
which extent pelvic dimorphism is a correlate of obstetric constraints, of body
size dimorphism, and/or of other factors. Also, little is known on how pelvic
dimorphism develops. Here we use methods of biomedical imaging and geometric
morphometrics to address these questions in two hylobatid species, Hylobates lar
and Symphalangus syndactylus. These species differ markedly in body size, but
within each species, there is only little body size dimorphism. Results show that
the neonates of H. lar are large compared to the maternal pelvis, resulting in
high cephalopelvic proportions and substantial obstetric constraints. Pelvic
sexual dimorphism is moderate but significant: During puberty, females develop a
more capacious pelvic inlet than males, while overall pelvic size is similar in
both sexes. S. syndactylus has substantially larger pelves than H. lar, but
neonates are similar in size to those of H. lar. Cephalopelvic proportions are
thus low, and there are no obstetric constraints. Pelvic sexual dimorphism is
absent. Overall, these data indicate that pelvic sexual dimorphism in hylobatids
reflects obstetric constraints. Anat Rec, 300:859-869, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28406563
TI - Evolution of the Human Pelvis.
AB - No bone in the human postcranial skeleton differs more dramatically from its
match in an ape skeleton than the pelvis. Humans have evolved a specialized
pelvis, well-adapted for the rigors of bipedal locomotion. Precisely how this
happened has been the subject of great interest and contention in the
paleoanthropological literature. In part, this is because of the fragility of the
pelvis and its resulting rarity in the human fossil record. However, new
discoveries from Miocene hominoids and Plio-Pleistocene hominins have reenergized
debates about human pelvic evolution and shed new light on the competing roles of
bipedal locomotion and obstetrics in shaping pelvic anatomy. In this issue, 13
papers address the evolution of the human pelvis. Here, we summarize these new
contributions to our understanding of pelvic evolution, and share our own
thoughts on the progress the field has made, and the questions that still remain.
Anat Rec, 300:789-797, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406564
TI - Neonatal Shoulder Width Suggests a Semirotational, Oblique Birth Mechanism in
Australopithecus afarensis.
AB - Birth mechanics in early hominins are often reconstructed based on cephalopelvic
proportions, with little attention paid to neonatal shoulders. Here, we find that
neonatal biacromial breadth can be estimated from adult clavicular length (R2 =
0.80) in primates. Using this relationship and clavicular length from adult
Australopithecus afarensis, we estimate biacromial breadth in neonatal
australopiths. Combined with neonatal head dimensions, we reconstruct birth in A.
afarensis (A.L. 288-1 or Lucy) and find that the most likely mechanism of birth
in this early hominin was a semi-rotational oblique birth in which the head
engaged and passed through the inlet transversely, but then rotated so that the
head and shoulders remained perpendicular and progressed through the midplane and
outlet oblique to the main axis of the female pelvis. Any other mechanism of
birth, including asynclitic birth, would have resulted in either the head or the
shoulders orthogonal to the short anteroposterior dimension of the A.L. 288-1
pelvis, making birth untenable. There is a tight fit between the infant and all
planes of the birth canal, perhaps suggesting a difficult labor in australopiths.
However, the rotational birth mechanism of large-brained humans today was likely
not characteristic of A. afarensis. Thus, the evolution of rotational birth,
usually associated with encephalization, may have occurred in two stages: the
first appeared with the origin of the australopiths with their platypelloid
pelves adapted for bipedalism and their broad-shouldered neonates; the second
which resulted in the modern mechanism of rotational birth may be associated with
increasing brain size in the genus Homo. Anat Rec, 300:890-899, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28406565
TI - Sacral Variability in Tailless Species: Homo sapiens and Ochotona princeps.
AB - Homo sapiens is variable in number of sacral vertebrae, and this variability can
lead to obstetrical complication. This study uses the comparative method to test
the hypothesis that sacral variability in H. sapiens is associated with absence
of a tail. Three species of lagomorphs are studied: Ochotona princeps (N = 271),
which is tailless, and Lepus californicus (N = 212) and Sylvilagus audubonii (N =
206), which have tails. Results show that O. princeps has (1) higher diversity
index for number of sacral vertebrae (0.49) compared to L. californicus (0.25)
and S. audubonii (0.26) and (2) significantly higher percentage of individuals
with the species-specific nonmodal number of sacral vertebrae (43.9%) compared to
L. californicus (14.2%) and S. audubonii (15.5%). Comparison of H. sapiens (N =
1,030; individuals of age 20-39 years) with O. princeps shows similarities
between the species in diversity index (also 0.49 in H. sapiens) and percentage
of individuals with nonmodal number of sacral vertebrae (37.3% in H. sapiens).
Homeotic transformation best explains the results. H. sapiens and O. princeps
show propensity for caudal shift at the sacral-caudal border (i.e., homeotic
transformation of the first caudal vertebra to a sacral vertebra). Caudal and
cranial shift among presacral vertebrae increases or decreases this propensity,
respectively. Increase in number of sacral vertebrae in H. sapiens by homeotic
transformation reduces pelvic outlet capacity and can be obstetrically hazardous.
Anat Rec, 300:798-809, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406566
TI - How Did the Pelvis and Vertebral Column Become a Functional Unit during the
Transition from Occasional to Permanent Bipedalism?
AB - The functional linkage between pelvis and spine remained long hidden to science.
Here, we recount the history of research that led in 1992 to the discovery of the
"angle of sacral incidence" by the team of G. Duval-Beaupere. This angle, formed
between a ray from the hip joint center to the superior sacral surface and the
perpendicular to the sacral surface, was later called pelvic incidence. Specific
to each individual, pelvic incidence is tightly correlated with the degree of
lumbar lordosis. It is each individual's "signature" for an efficient sagittal
balance since it represents the sum of two positional parameters, sacral slope
and pelvic tilt. The simultaneous experimental determination of the trunk line of
gravity permitted Duval-Beaupere's team to elucidate the conditions of an
efficient sagittal balance of the trunk on the lower limbs. We present an in vivo
EOS study of eight spino-pelvic parameters describing the sagittal balance in 131
adults. We observe a chain of correlations between the six angular parameters and
discuss the functional significance of these results. We show that pelvic
incidence increases and lumbar lordosis develops when the infant learns to walk,
leading to a correlation between these parameters. This process of association
between pelvis and spine might have acquired a solid genetic basis during hominid
evolution by natural selection acting on both pelvis and spine. We suggest that
this process of functional integration was only possible in the context of
bipedal locomotion becoming permanent and stereotyped, expressed by a relatively
invariant, periodic walking cycle. Anat Rec, 300:912-931, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28406567
TI - Evolution of Spinopelvic Alignment in Hominins.
AB - Spinopelvic alignment refers to the interaction between pelvic orientation,
spinal curvatures, and the line of gravity. In a healthy modern human, this
alignment is characterized by reciprocal curves/orientation of the sacrum, lumbar
lordosis, thoracic kyphosis, and cervical lordosis. In an economic sagittal
posture, these curvatures keep the line of gravity close to the center of the
acetabulum. The purpose of this study is to explore the spinopelvic alignment in
extinct hominins. We examined spinopelvic alignment of a single representative
from each of the following hominin groups: Australopithecus, Homo erectus (H.
erectus), H. neanderthalensis, and early H. sapiens. Pelvic incidence, lumbar
lordosis, thoracic kyphosis, and cervical lordosis for each representative was
estimated and compared with that of modern humans. Three basic spinopelvic
alignments were found: (1) the sinusoidal alignment with moderate to high spinal
curvatures and pelvic incidence found in H. erectus and H. sapiens; (2) the
straight alignment with small spinal curvatures and small pelvic incidence found
in Neandertal lineage hominins; (3) the compound alignment found in
Australopithecus, with moderate pelvic incidence and lumbar lordosis, and nearly
straight cervical spine. Our results indicate that balanced upright posture can
be achieved in different alignments. Each hominin group solved the requirements
of erect posture in a slightly different way. Moreover, we propose the term
"cranio-spino-pelvic balance" to substitute "spino-pelvic balance." From an
evolutionary perspective, not only changes in the pelvis have conditioned the
evolution of the spinal curvatures but also changes in the equilibrium of the
head likely also affected this balance. Anat Rec, 300:900-911, 2017. (c) 2017
Wiley Periodicals, Inc.
PMID- 28406568
TI - Dimorphism in the Size and Shape of the Birth Canal Across Anthropoid Primates.
AB - It has long been noted that the human female birth canal is well adapted to
giving birth to large-brained neonates. However, several species of nonhuman
primates give birth to large-headed neonates compared to the maternal birth
canal. The presence of such large cephalopelvic proportions in nonhuman primates
presents the question of whether dimorphism in the birth canals of these other
species is related to obstetric demand, as such dimorphism is presumed to be in
humans. In this study, the hypothesis that either the presence or magnitude of
dimorphism in the birth canal is related to large cephalopelvic proportions among
anthropoid primates is directly tested. This study shows that birth canal
dimorphism is common among anthropoids regardless of cephalopelvic proportions,
but taxa with large cephalopelvic proportions have a higher magnitude of
dimorphism than those that give birth to relatively small-headed neonates.
Furthermore, humans have exceptionally high levels of dimorphism that cannot be
explained based on our large cephalopelvic proportions alone. Anat Rec, 300:870
889, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406569
TI - Ischial Form as an Indicator of Bipedal Kinematics in Early Hominins: A Test
Using Extant Anthropoids.
AB - Human ischia contrast with those of great apes in being craniocaudally short and
dorsally projecting. This configuration is thought to facilitate greater hip
extension in humans during bipedal locomotion. This link has been used to infer
kinematics in early hominins, but the consequences of variation in ischial
configuration for gait remain uncertain. Kinematic data for a limited sample of
extant nonhuman primates demonstrate that there is variation in hip extension in
these taxa during bipedal behaviors-specifically, Hylobates and Ateles are
capable of greater extension than Pan and Macaca. In this study, we tested the
hypothesis that ischial length and orientation are functionally linked with hip
extension during bipedalism among these taxa. As expected, humans have the
shortest ischia, followed by gibbons, spider monkeys, chimpanzees, and macaques.
Our predictions for ischial orientation are not supported, however: macaques,
gibbons, and spider monkeys do not vary in this trait, and they have ischia that
are less dorsally angled than that of the chimpanzee. The results for ischium
length provide limited support for the idea that the early hominin Ardipithecus
ramidus, with its long, caudally oriented ischium was not capable of humanlike
extended-hip bipedalism, and that the ischial shortening observed in post
Ardipithecus hominins reflects a shift toward a more humanlike gait. In contrast,
while our results do not necessarily refute a link between ischial orientation
and hip extension in hominins, they do not provide comparative support, making
changes in ischial orientation in this part of the fossil record more difficult
to interpret. Anat Rec, 300:845-858, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406570
TI - Pelvic Morphology in Homo erectus and Early Homo.
AB - The evolution of the hominin pelvis is generally seen as involving two broad
stages: the establishment of bipedal pelvic morphology by the mid-Pliocene (or
earlier), followed by architectural changes necessary to enlarge the birth canal
in response to increased encephalization in Pleistocene members of the genus
Homo. Pelvic and proximal femoral morphology in early Homo (namely H. erectus)
has been seen as transitional between these stages, reflecting structural changes
necessitated by greater body size (and perhaps moderate increases in brain size)
overlain upon a basically primitive pelvic architecture. Here we review the
history of thought on the evolution of the pelvis in early Homo, as well as
recent fossil discoveries that have improved our understanding of diversity in
pelvic morphology in early Homo and late australopiths. These discoveries (1)
suggest that the "femoropelvic complex" characteristic of H. erectus emerged
after the divergence of various lineages of early Homo (that is, it is not
plesiomorphic for the genus) and (2) raise questions about the role that
evolutionary change in brain size in the genus Homo played in the emergence of
derived features seen in the pelvis of modern humans. Anat Rec, 300:964-977,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406571
TI - Hominin Hip Biomechanics: Changing Perspectives.
AB - The shape of the human pelvis reflects the unique demands placed on the hip
abductor muscles (gluteus medius and gluteus minimus), which stabilize the body
in the frontal plane during bipedal locomotion. This morphological shift occurred
early in hominin evolution, yet important shape differences between hominin
species have led to significant disagreement about abductor function and
locomotor capability in these extinct taxa. A static biomechanical model that
relies on a close association between skeletal measurements of the pelvis and
femur has traditionally been used to reconstruct hip biomechanics in these
species. However, experimental biomechanical approaches have highlighted the
dynamic nature of mediolateral balance in walking and running, challenging the
assumptions of the static hip model. This article reviews traditional approaches
for understanding hip abductor function, shows how they have been applied to the
fossil hominin record, and discusses new techniques that integrate the dynamic
nature of mediolateral balance during human locomotion. Anat Rec, 300:932-945,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28406572
TI - Review article: Workplace violence in the emergency department: A systematic
review and meta analysis.
AB - Patient or visitor perpetrated workplace violence (WPV) has been reported to be a
common occurrence within the ED. No universal definition of violence or recording
of such events exists. In addition ED staff are often reluctant to report violent
incidents. The true incidence of WPV is therefore unclear. This systematic review
aimed to quantify WPV in EDs. The association of WPV to drug and alcohol exposure
was explored. The databases MEDLINE, Embase, PsycInfo and the Cochrane Library
were searched from their commencement to 10 March 2016. MeSH terms and text words
for ED, violence and aggression were combined. A meta-analysis was conducted on
the primary outcome variable-proportion of violent patients among total ED
presentations. A secondary meta-analysis used studies reporting on proportion of
drug and alcohol affected patients occurring within the violent population. The
search yielded a total of 8720 records. A total of 7235 were unique and underwent
abstract screening. A total of 22 studies were deemed relevant according to
inclusion and exclusion criteria. Retrospective study design predominated,
analysing mainly security records and incident reports. The rates of violence
from individual studies ranged from 1 incident to 172 incidents per 10 000
presentations. The pooled incidence suggests there are 36 violent patients for
every 10 000 presentations to the ED (95% confidence interval 0.0030-0.0043). WPV
in the ED was commonly reported. There is wide heterogeneity across the study
methodology, definitions and rates. More standardised recording and reporting may
inform preventive measures and highlight effective management strategies.
PMID- 28406573
TI - Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural
Progenitor Cells During Development.
AB - Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ)
of the lateral ganglionic eminence is an active process throughout early brain
development. The migration of human NPCs from the SVZ to the olfactory bulb
during fetal stages resembles what occurs in adult rodents. As the human brain
develops during infancy, this migratory stream is drastically reduced in cell
number and becomes barely evident in adults. The mechanisms regulating human NPC
migration are unknown. The Slit-Robo signaling pathway has been defined as a
chemorepulsive cue involved in axon guidance and neuroblast migration in rodents.
Slit and Robo proteins expressed in the rodent brain help guide neuroblast
migration from the SVZ through the rostral migratory stream to the olfactory
bulb. Here, we present the first study on the role that Slit and Robo proteins
play in human-derived fetal neural progenitor cell migration (hfNPC). We describe
that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore,
we demonstrate that Slit2 is able to induce a chemorepellent effect on the
migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1
expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of
mice when injected in the anterior SVZ. Our findings indicate that the migration
of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This
pathway could be regulated to direct the migration of NPCs in human endogenous
neural cell therapy. Stem Cells 2017;35:1860-1865.
PMID- 28406574
TI - Antitumor effect of focal adhesion kinase inhibitor PF562271 against human
osteosarcoma in vitro and in vivo.
AB - Focal adhesion kinase (FAK) overexpression is related to invasive and metastatic
properties in different kinds of cancers. Target therapy by inhibiting FAK has
achieved promising effect in some cancer treatments, but its effect in human
osteosarcoma has not been well studied. In the present study, we analyzed the
antitumor efficacy of PF562271, an FAK inhibitor, against osteosarcoma in vitro
and in vivo. Phosphorylated FAK (Y397) was highly expressed in primary human
osteosarcoma tumor samples and was associated with osteosarcoma prognosis and
lung metastasis. PF562271 greatly suppressed proliferation and colony formation
in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell
lines with PF562271 induced apoptosis and downregulated the activity of the
protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired
the tube formation ability of endothelial cells in vitro. Finally, oral treatment
with PF562271 in mice dramatically reduced tumor volume, weight, and angiogenesis
of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor
PF562271 can potentially be effectively used for the treatment of osteosarcoma.
PMID- 28406575
TI - Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with
thrombin generation assay and factor IX activity.
AB - INTRODUCTION: Prophylaxis is the recommended treatment mode for severe hemophilia
B. However, no single treatment regimen fits for all patients. Once-weekly
prophylaxis with high-dose recombinant factor IX (rFIX) is efficacious,
nevertheless, laboratory outcomes following 72 h after administration are
lacking. METHODS: In a prospective open-label noncomparative study, 10
severe/moderate (FIX <=2 IU/dL) adult patients received rFIX dose (60-100 IU/kg)
after >72 h washout on two occasions, separated by 7 days. We measured one-stage
and chromogenic FIX, ROTEM, and thrombin generation (TG) assay in plasma after
washout, 30 min after infusion, and at days 3, 4, and 7. RESULTS: Median FIX
clotting/chromogenic activity increased from 1.5/2.0 to 87/62 IU/dL following
rFIX administration, chromogenic assay resulting in 30% lower recovery.
Correspondingly TG was severely reduced at baseline and improved at recovery
(peak thrombin 6.0 to 54 nm). Standard ROTEM failed to detect FIX deficiency.
Both FIX activity and TG remained increased from days 3 to 7, with median trough
levels of FIX clotting/chromogenic 3.0/3.0 IU/dL (>=1 IU/dL in all severe
patients) and peak thrombin 9.1 nm measured on day 7. FIX and TG assays were
equally consistent between weeks 1 and 2. CONCLUSIONS: Once-weekly rFIX
prophylaxis results in favorable laboratory outcome.
PMID- 28406576
TI - Antitumor activity and pharmacologic characterization of the depsipeptide analog
as a novel histone deacetylase/ phosphatidylinositol 3-kinase dual inhibitor.
AB - Histone deacetylase (HDAC)/phosphatidylinositol 3-kinase (PI3K) dual inhibition
is a promising strategy for the treatment of intractable cancers because of the
advantages of overcoming potential resistance and showing synergistic effects.
Therefore, development of an HDAC/PI3K dual inhibitor is reasonably attractive.
Romidepsin (FK228, depsipeptide) is a potent HDAC inhibitor. We previously
reported that depsipeptide and its analogs have an additional activity as PI3K
inhibitors and are defined as HDAC/PI3K dual inhibitors. Subsequently, we
identified FK-A11 as the most potent analog and reported its biochemical,
biological, and structural properties as an HDAC/PI3K dual inhibitor. In this
study, we reveal the in vitro and in vivo efficacy of FK-A11 in HT1080
fibrosarcoma and PC3 prostate cancer cell xenograft mouse models. FK-A11 showed
in vivo antitumor activity by both i.v. and i.p. administration in a dose
dependent manner. In both xenograft models, FK-A11 showed superior antitumor
effects compared to other depsipeptide analogs in accordance with in vitro anti
cell proliferation effects and the potency of HDAC/PI3K dual inhibition. In
addition, we showed evidence of HDAC/PI3K dual inhibition accompanying antitumor
efficacy in xenograft tumor tissues by immunohistochemistry. We also detailed
pharmacokinetic characterization of FK-A11 in mice. These findings will be
essential for guiding further preclinical and clinical studies.
PMID- 28406577
TI - Evidence of African horse sickness virus infection of Equus zebra hartmannae in
the south-western Khomas Region, Namibia.
AB - Equine mortalities suspected to be due to African horse sickness (AHS) were
reported from the arid Khomas Region, Namibia, in 2008. The area was previously
considered a localized AHS-free area. Hartmann's mountain zebra (Equus zebra
hartmannae), a potential but unconfirmed reservoir host of African horse sickness
virus (AHSV), occurs in the region. Between 2009 and 2010 serum, blood and tissue
samples from 31 culled E. z. hartmannae were analysed by reverse transcription
polymerase chain reaction (RT-PCR) (n = 31) and enzyme-linked immunosorbent assay
(ELISA) (n = 18) to determine the presence of AHSV and/or antibodies against
AHSV. The presence of antibodies against AHSV was demonstrated in all 18 samples
assayed, and AHSV double stranded RNA was detected in 26% of the animals. This is
evidence that E. z. hartmannae can become infected with AHSV.
PMID- 28406578
TI - Production of Biomass-Based Automotive Lubricants by Reductive Etherification.
AB - Growing concern with the effects of CO2 emissions due to the combustion of
petroleum-based transportation fuels has motivated the search for means to
increase engine efficiency. The discovery of ethers with low viscosity presents
an important opportunity to improve engine efficiency and fuel economy. We show
here a strategy for the catalytic synthesis of such ethers by reductive
etherification/O-alkylation of alcohols using building blocks that can be sourced
from biomass. We find that long-chain branched ethers have several properties
that make them superior lubricants to the mineral oil and synthetic base oils
used today. These ethers provide a class of potentially renewable alternatives to
conventional lubricants produced from petroleum and may contribute to the
reduction of greenhouse gases associated with vehicle emissions.
PMID- 28406579
TI - Disparities in pharmacotherapy for alcohol use disorder in the context of
universal health care: a Swedish register study.
AB - BACKGROUND AND AIMS: Pharmacotherapy can be an important part of the continuum of
care for alcohol use disorder (AUD). The Swedish universal health-care system
emphasizes provision of care to marginalized groups. The primary aim was to test
associations of neighborhood deprivation and disadvantaged social status with
receipt of AUD pharmacotherapy in this context. DESIGN: Data from linked
population registers were used to follow an open cohort over 7 years. SETTING:
Sweden. PARTICIPANTS: Alcohol-related ICD-10 codes reported for all
hospitalizations in the Swedish Hospital Discharge Register and all clinic/office
visits in the Outpatient Care Register between 2005 and 2012 were used to
identify 62 549 cases with AUD. MEASUREMENTS: The primary outcome was any AUD
pharmacotherapy (naltrexone, disulfiram, acamprosate, nalmefene) picked up by
patients between 2005 and 2012 (versus none), based on the Swedish Prescribed
Drug Register. Neighborhood deprivation was defined using aggregated data from
the Total Population Register; indicators of disadvantaged social status (income,
education, country of origin) also came from this source. FINDINGS: Approximately
half the cases (53.7%) picked up one or more AUD pharmacotherapy prescriptions.
In adjusted models, people living in neighborhoods with moderate [odds ratio (OR)
= 0.90, 95% confidence interval (CI) = 0.86, 0.95] or high levels of deprivation
(OR = 0.75, 95% CI = 0.70, 0.79) compared with low deprivation, those with lower
incomes (for example, lowest quartile: OR = 0.70, 95% CI = 0.66, 0.73 compared
with highest) and less education (for example, < 10 years: OR = 0.82, 95% CI =
0.78, 0.85 compared with 12+ years) and people born outside Sweden (OR = 0.74,
95% CI = 0.71, 0.78 compared with Swedish-born) were significantly less likely to
pick up a prescription for AUD pharmacotherapy during the study period.
CONCLUSIONS: There appear to be socio-economic disparities in the receipt of
pharmacotherapy for alcohol use disorder in Sweden.
PMID- 28406581
TI - Comment on "Tunable Design of Structural Colors Produced by Pseudo-1D Photonic
Crystals of Graphene Oxide" and Thin-Film Interference from Dried Graphene Oxide
Film.
AB - The mechanism of the iridescent color reflection from dried thin graphene oxide
(GO) film on Si wafer is clarified. Dissimilarly to the photonic crystalline
reflection in aqueous GO dispersion, the color reflection in dried GO film
originates from the thin film interference. The peak reflection can reach 23% by
optimizing the GO thickness and the substrate.
PMID- 28406580
TI - Low glucose induces mitochondrial reactive oxygen species via fatty acid
oxidation in bovine aortic endothelial cells.
AB - AIMS/INTRODUCTION: Overproduction of reactive oxygen species (ROS) in endothelial
cells (ECs) plays a pivotal role in endothelial dysfunction. Mitochondrial ROS
(mtROS) is one of the key players in the pathogenesis of diabetic vascular
complications. Hypoglycemia is linked to increased ROS production and vascular
events; however, the underlying mechanisms remain unclear. In the present study,
we aimed to determine whether and how low glucose (LG) mediates mtROS generation
in ECs, and to examine the impact of LG-induced mtROS on endothelial dysfunction.
MATERIALS AND METHODS: Metabolomic profiling, cellular oxygen consumption rate,
mtROS, endothelial nitric oxide synthase phosphorylation, and the expression of
vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 were
evaluated in bovine aortic ECs. RESULTS: We found that LG increased mtROS
generation in ECs; which was suppressed by overexpression of manganese superoxide
dismutase. Comprehensive metabolic analysis using capillary electrophoresis-mass
spectrometry and oxygen consumption rate assessment showed that the pathway from
fatty acid to acetyl-CoA through fatty acid oxidation was upregulated in ECs
under LG conditions. In addition, etomoxir, a specific inhibitor of the free
fatty acid transporter, decreased LG-induced mtROS production. These results
suggested that LG increased mtROS generation through activation of fatty acid
oxidation. We further revealed that LG inhibited endothelial nitric oxide
synthase phosphorylation, and increased the expression of vascular cell adhesion
molecule-1 and intercellular adhesion molecule-1. These effects were suppressed
either by overexpression of manganese superoxide dismutase or by treatment with
etomoxir. CONCLUSIONS: The activation of fatty acid oxidation followed by mtROS
production could be one of the causes for endothelial dysfunction during
hypoglycemia.
PMID- 28406582
TI - Response to "Comment on 'Tunable Design of Structural Colors Produced by Pseudo
1D Photonic Crystals of Graphene Oxide' and Thin-Film Interference from Dried
Graphene Oxide Film".
AB - The structural colors produced by pseudo-1D photonic crystals of graphene oxide
originate from the regularly layered structure of GO films, which have been
previously reported. For the same observation regarding the tunable color
reflection obtained from the dried GO films, Hong et al. suggest a different
mechanism to the previously published model.
PMID- 28406583
TI - People, Practices, and Places: Realities That Influence Evidence-Based Practice
Uptake.
PMID- 28406584
TI - Thick Corpus Callosum in Children.
AB - BACKGROUND AND PURPOSE: A thick corpus callosum (TCC) can be associated with a
very grave outcome in fetuses, but its clinical presentation in older children
seems to be markedly different. METHODS: The corpus callosum (CC) was defined as
thick based on observations and impressions. We reviewed cases of children who
were diagnosed as TCC based on brain magnetic resonance imaging (MRI) studies.
The pertinent clinical data of these children were collected, and their CCs were
measured. RESULTS: Out of 2,552 brain MRI images, those of 37 children were
initially considered as showing a TCC. Those initial imaging were reviewed by an
experienced neuroradiologist, who confirmed the diagnosis in 34 children (1.3%):
13 had neurofibromatosis-1 (NF-1), 9 had epilepsy, 3 had macrocephaly capillary
malformation (MCM) syndrome, 3 had autistic spectrum disorder, 1 had a Chiari-1
malformation, and 1 had increased head circumference. No specific neurologic
disorder could be defined in seven children. The measured thickness of the CC in
these children was comparable to those published in the literature for adults.
CONCLUSIONS: A TCC is a rare brain malformation that can be found in
neuropathologies with apparently diverse pathognomonic mechanisms, such as NF-1
and MCM. It is not necessarily associated with life-threatening conditions,
instead being a relatively benign finding, different in nature from that reported
in fetuses.
PMID- 28406585
TI - Association of Helicobacter pylori with Parkinson's Disease.
AB - BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a major neurological disorder
that requires lifelong treatment, and the combined presence of Helicobacter
pylori (H. pylori) infection can increase the required anti-PD medications. We
aim to investigate the effect of H. pylori infection in Indian PD patients.
METHODS: We prospectively recruited 36 PD patients from December 2007 to January
2011. All patients underwent a detailed neurological evaluation and serological
examination for H. pylori infection. Seropositive and seronegative patients were
considered to be the cases and controls, respectively. All patients who were
seropositive received triple therapy for 2 weeks. Outcome measures of the mean
'off' Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean 'on' UPDRS
III score, mean onset time, mean 'on' duration, and mean daily 'on' time were
measured at baseline and at a 3-week follow-up. RESULTS: H. pylori-IgG positivity
was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%),
mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose
(824 mg vs. 707 mg) were significantly higher among H. pylori positive patients
than in controls (p<0.0001). Controls had a significantly longer 'on' duration
and daily 'on' time, and better 'on' UPDRS-III scores. Seropositive patients took
a significantly longer time to turn 'on' after a levodopa challenge. At the 3
week follow-up, H. pylori eradication significantly improved the mean 'on' UPDRS
III score, onset time, 'on' duration, and daily 'on' time. CONCLUSIONS: H. pylori
infection was present in 50% of Indian PD patients. H. pylori seropositivity was
associated with a poor response to levodopa and increased medication usage, while
eradication therapy was associated with better patient outcomes.
PMID- 28406586
TI - Total Cerebral Small-Vessel Disease Score is Associated with Mortality during
Follow-Up after Acute Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: The recently developed total cerebral small-vessel
disease (CSVD) score might appropriately reflect the total burden or severity of
CSVD. We investigated whether the total CSVD score is associated with long-term
outcomes during follow-up in patients with acute ischemic stroke. METHODS: In
total, 1,096 consecutive patients with acute ischemic stroke who underwent brain
magnetic resonance imaging were enrolled. We calculated the total CSVD score for
each patient after determining the burden of cerebral microbleeds (CMBs), high
grade white-matter hyperintensities (HWHs), high-grade perivascular spaces
(HPVSs), and asymptomatic lacunar infarctions (ALIs). We recorded the date and
cause of death for all of the patients using data from the Korean National
Statistical Office. We compared the long-term mortality rate with the total CSVD
score using Cox proportional-hazards models. RESULTS: CMBs were found in 26.8% of
the subjects (294/1,096), HWHs in 16.4% (180/1,096), HPVSs in 19.3% (211/1,096),
and ALIs in 38.0% (416/1,096). After adjusting for age, sex, and variables that
were significant at p<0.1 in the univariate analysis, the total CSVD score was
independently associated with long-term death from all causes [hazard ratio
(HR)=1.18 per point, 95% confidence interval (CI)=1.07-1.30], ischemic stroke
(HR=1.20 per point, 95% CI=1.01-1.42), and hemorrhagic stroke (HR=2.05 per point,
95% CI=1.30-3.22), but not with fatal cardiovascular events (HR=1.17 per point,
95% CI=0.82-1.67). CONCLUSIONS: The total CSVD score is a potential imaging
biomarker for predicting mortality during follow-up in patients with acute
ischemic stroke.
PMID- 28406587
TI - Reversible Corpus Callosal Lesions Associated with the Use of Adalimumab for
Ulcerative Colitis.
PMID- 28406588
TI - Comments on "Neuromuscular Ultrasonography of Cranial Nerves".
PMID- 28406589
TI - Re: Comments on "Neuromuscular Ultrasonography of Cranial Nerves": The Authors
Respond.
PMID- 28406590
TI - [Acute renal failure].
PMID- 28406591
TI - [Chronic renal failure].
PMID- 28406592
TI - [Acute pyelonephritis].
PMID- 28406593
TI - [Chronic pyelonephritis].
PMID- 28406594
TI - [Cystitis].
PMID- 28406597
TI - Adolescents' experience of a rapid HIV self-testing device in youth-friendly
clinic settings in Cape Town South Africa: a cross-sectional community based
usability study.
AB - Introduction: Since HIV testing in South African adolescents and young adults is
sub-optimal, the objective of the current study was to investigate the
feasibility and acceptability of an HIV rapid self-testing device in adolescents
and young people at the Desmond Tutu HIV Foundation Youth Centre and Mobile
Clinic. Methods: Self-presenting adolescents and young adults were invited to
participate in a study investigating the fidelity, usability and acceptability of
the AtomoRapid HIV Rapid self-testing device. Trained healthcare workers trained
participants to use the device before the participant conducted the HIV self-test
with device usage instructions. The healthcare worker then conducted a
questionnaire-based survey to assess outcomes. Results: Of the 224 enrolled
participants between 16 and 24 years of age, 155 (69,2%) were female. Overall,
fidelity was high; 216 (96,4%) participants correctly completed the test and
correctly read and interpreted the HIV test result. There were eight (3,6%) user
errors overall; six participants failed to prick their finger even though the
lancet fired correctly. There were two user errors where participants failed to
use the capillary tube correctly. Participants rated acceptability and usability
highly, with debut testers giving significantly higher ratings for both. Younger
participants gave significantly higher ratings of acceptability. Conclusions:
Adolescents and young adults found HIV self-testing highly acceptable with the
AtomoRapid and they used the device accurately. Further research should
investigate how, where and when to deploy HIV self-testing as a means to
accompany existing strategies in reaching the UNAIDS goal to test 90% of all
individuals worldwide.
PMID- 28406595
TI - Changes in estimated glomerular filtration rate over time in South African HIV-1
infected patients receiving tenofovir: a retrospective cohort study.
AB - INTRODUCTION: Tenofovir has been associated with decline in kidney function, but
in patients with low baseline kidney function, improvements over time have been
reported. Additionally, the magnitude and trajectory of estimated glomerular
filtration rate (eGFR) changes may differ according to how eGFR is calculated. We
described changes in eGFR over time, and the incidence of, and risk factors for,
kidney toxicity, in a South African cohort. METHODS: We included antiretroviral
naive patients >=16 years old who started tenofovir-containing antiretroviral
therapy (ART) between 2002 and 2013. We calculated eGFR using the Modification of
Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI), and Cockcroft-Gault equations. We described changes in eGFR from ART
initiation using linear mixed effects regression. We described the incidence of
eGFR <30 mL/min on treatment, and identified associations with low eGFR using Cox
regression. RESULTS: We included 15156 patients with median age of 35.4 years
(IQR 29.9-42.0), median CD4 cell count of 168 cells/uL (IQR 83-243), and median
eGFR (MDRD) of 98.6 mL/min (IQR 84.4-115.6). Median duration of follow up on
tenofovir was 12.9 months (IQR 5.1-23.3). Amongst those with a baseline and
subsequent eGFR available, mean eGFR change from baseline at 12 months was -4.4
mL/min (95% CI -4.9 to -4.0), -2.3 (-2.5 to -2.1), and 0.6 (0.04 to 1.2) in those
with baseline eGFR >=90 mL/min; and 11.9 mL/min (11.0 to 12.7), 14.6 (13.5 to
15.7), and 11.0 (10.3 to 11.7), in those with baseline eGFR <90 mL/min, according
to the MDRD, CKD-EPI (n = 11 112), and Cockcroft-Gault (n = 9 283) equations,
respectively. Overall, 292 (1.9%) patients developed eGFR <30 mL/min. Significant
associations with low eGFR included older age, baseline eGFR <60 mL/min, CD4
count <200 cells/uL, body weight <60 kg, and concomitant protease inhibitor use.
CONCLUSION: Patients on tenofovir with baseline eGFR >=90 mL/min experienced
small but significant declines in eGFR over time when eGFR was estimated using
the MDRD or CKD-EPI equations. However, eGFR increased in patients with eGFR <90
mL/min, regardless of which estimating equation was used. Decreases to below 30
mL/min were uncommon. In settings with limited access to laboratory testing,
monitoring guidelines should consider focusing on higher risk patients.
PMID- 28406596
TI - Improving early identification of HIV-infected neonates with birth PCR testing in
a large urban hospital in Johannesburg, South Africa: successes and challenges.
AB - INTRODUCTION: Timely diagnosis is necessary to avert early death in HIV-infected
neonates. Birth PCR testing may improve early identification and facilitate
access to care. We implemented a birth HIV diagnosis programme in Johannesburg,
South Africa and present successes and challenges of the first two and a half
years of operation. METHODS: Between June 2014 and December 2016, we sought to
identify all HIV-exposed births and offer newborn HIV PCR testing before
discharge after delivery. The programme identified newly delivered women who had
tested positive during pregnancy and provided post-partum HIV antibody testing
for women without recent negative results. HIV-positive women were required to
consent for neonatal birth testing and asked to return a week later to obtain
their results. Neonatal venous blood was sampled and tested at the national
laboratory using Roche COBAS(r) TaqMan(r) HIV-1 Qualitative Test (Version 2.0).
Non-negative results triggered active follow-up for confirmatory testing and
appropriate treatment. RESULTS: Of 30,591 women with live births, 6864 (22.4%)
were known to be HIV positive and an additional 221 women (1.4% of those tested)
were identified during maternal postnatal testing. Of 7085 HIV-positive women,
6372 (89.9%) were interviewed and agreed to data collection, 6358 (99.8%)
consented to birth testing for 6467 neonates and a blood sample was collected for
6377 (98.6%). If tested, 6210 (97.4%) tested negative, 91 (1.4%) positive, 57
(0.9%) revealed errors and 19 (0.3%) were indeterminate . Seven of the 19
neonates with indeterminate results and one with initial error result were found
to be infected on subsequent testing yielding an intrauterine transmission rate
of 1.6% (95% CI: 1.3-1.9). Sixteen (16%) of 99 infected infants were born to
women (n = 221) identified during postnatal testing. With active outreach, 95/99
(96%) infected infants were initiated on antiretroviral therapy. Of 6261 neonates
with negative results, 3251 (52%) returned to receive their test results.
CONCLUSION: Our programme successfully achieved high coverage and uptake of birth
PCR testing and was able, with active tracking, to start almost all identified
HIV-infected neonates on antiretroviral therapy. Implementation required
additional staff for counselling, quality control and outreach. Return for
negative results was low and neonates with indeterminate results required
multiple repeat tests.
PMID- 28406603
TI - Jonathan W. Amy and the Amy Facility for Instrumentation Development.
AB - This Perspective describes the unique Jonathan Amy Facility for Chemical
Instrumentation in the Department of Chemistry at Purdue University, tracing its
history and mode of operation. It also describes aspects of the career of its
namesake and some of his insights which have been central to analytical
instrumentation development, improvement, and utilization, both at Purdue and
nationally.
PMID- 28406598
TI - Factors associated with sex work involvement among transgender women in Jamaica:
a cross-sectional study.
AB - INTRODUCTION: Transgender women are disproportionately impacted by HIV.
Transgender women involved in sex work may experience exacerbated violence,
social exclusion, and HIV vulnerabilities, in comparison with non-sex work
involved transgender women. Scant research has investigated sex work among
transgender women in the Caribbean, including Jamaica, where transgender women
report pervasive violence. The study objective was to examine factors associated
with sex work involvement among transgender women in Jamaica. METHODS: In 2015,
we implemented a cross-sectional survey using modified peer-driven recruitment
with transgender women in Kingston and Ocho Rios, Jamaica, in collaboration with
a local community-based AIDS service organization. We conducted multivariable
logistic regression analyses to identify factors associated with paid sex and
transactional sex. Exchanging oral, anal or vaginal sex for money only was
categorized as paid sex. Exchanging sex for survival needs (food, accommodation,
transportation), drugs or alcohol, or for money along with survival needs and/or
drugs/alcohol, was categorized as transactional sex. RESULTS: Among 137
transgender women (mean age: 24.0 [SD: 4.5]), two-thirds reported living in the
Kingston area. Overall, 25.2% reported being HIV-positive. Approximately half (n
= 71; 51.82%) reported any sex work involvement, this included sex in exchange
for: money (n = 64; 47.06%); survival needs (n = 27; 19.85%); and drugs/alcohol
(n = 6; 4.41%). In multivariable analyses, paid sex and transactional sex were
both associated with: intrapersonal (depression), interpersonal (lower social
support, forced sex, childhood sexual abuse, intimate partner violence, multiple
partners/polyamory), and structural (transgender stigma, unemployment) factors.
Participants reporting transactional sex also reported increased odds of
incarceration perceived to be due to transgender identity, forced sex,
homelessness, and lower resilience, in comparison with participants reporting no
sex work involvement. CONCLUSION: Findings reveal high HIV infection rates among
transgender women in Jamaica. Sex work-involved participants experience social
and structural drivers of HIV, including violence, stigma, and unemployment.
Transgender women involved in transactional sex also experience high rates of
incarceration, forced sex and homelessness in comparison with non-sex workers.
Taken together, these findings suggest that social ecological factors elevate HIV
exposure among sex work-involved transgender women in Jamaica. Findings can
inform interventions to advance human rights and HIV prevention and care cascades
with transgender women in Jamaica.
PMID- 28406604
TI - An Efficient and Benign Antimicrobial Depot Based on Silver-Infused MoS2.
AB - Silver nanoparticles (AgNPs) have been used as a broad-spectrum antimicrobial
agent, whose toxicity originates from the localized release of Ag+ ions. However,
the residual AgNPs core could generate potential risk to humans and waste of
noble metals. Herein, we infused the cysteine-modified molybdenum disulfide with
minimum Ag+ ions and coated with a layer of cationic polyelectrolyte to construct
an efficient and benign antimicrobial depot. The system exhibited much enhanced
broad-spectrum antibacterial activity compared with an equivalent amount of
silver nitrate, owing to its increasing accessibility of released Ag+ to the cell
walls of microorganisms. More importantly, the antibacterial system could be
successfully applied to treat wound infection, while retaining high antibacterial
activities, exhibiting negligible biotoxicity and avoiding the waste of Ag.
PMID- 28406605
TI - Porous Nanobimetallic Fe-Mn Cubes with High Valent Mn and Highly Efficient
Removal of Arsenic(III).
AB - Iron (Fe) oxides are the most commonly used adsorbent materials for the aqueous
removal of Arsenic (As), but they have deficiencies, including low uptake and
poor removal of the relatively higher toxicity As(III). Introduction of
transition metals into Fe-containing adsorbents, an inexpensive method of
altering Fe chemical states, is likewise of interest for removing As(III) from
water by means of adsorption. Porous cubic Fe-Mn structures with BET surface area
of 450 m2 g-1 were herein prepared via chemical etching of Mn-substituted
Prussian Blue analogues (PBAs). Cyclic voltammetry showed a "protective" role of
polyvinylpyrrolidone (PVP) during the preparation process, so that Mn with high
valence state was readily preserved in this binuclear corner-sharing structure.
The calculated reaction Gibbs free energy, which was the most negative of the
studied adsorbents, indicated that the adsorption was promoted in the presence of
high valence Mn. The structures were capable of directly capturing As(III)
oxyanions to below the acceptable limits in drinking water standards, and the
saturation uptake capacity of 460 mg g-1 was substantially higher than comparable
materials under consideration. The work therefore presents a new benchmark for As
adsorbent materials and demonstrates the promise of the porous Fe-Mn structure
for rapid removal of other metal ions from contaminated water for environmental
remediation.
PMID- 28406607
TI - Beyond Wicking: Expanding the Role of Patterned Paper as the Foundation for an
Analytical Platform.
AB - While a number of assays for soluble analytes have been developed using paper
based microfluidic devices, the detection and analysis of blood cells has
remained an outstanding challenge. In this Feature, we discuss how the properties
of paper determine the performance of paper-based microfluidic devices and permit
the design of cellular assays, which can ultimately impact disparities in
healthcare that exist in limited-resource settings.
PMID- 28406606
TI - Characterization of Complete Histone Tail Proteoforms Using Differential Ion
Mobility Spectrometry.
AB - Histone proteins are subject to dynamic post-translational modifications (PTMs)
that cooperatively modulate the chromatin structure and function. Nearly all
functional PTMs are found on the N-terminal histone domains (tails) of ~50
residues protruding from the nucleosome core. Using high-definition differential
ion mobility spectrometry (FAIMS) with electron transfer dissociation, we
demonstrate rapid baseline gas-phase separation and identification of tails
involving monomethylation, trimethylation, acetylation, or phosphorylation in
biologically relevant positions. These are by far the largest variant peptides
resolved by any method, some with PTM contributing just 0.25% to the mass. This
opens the door to similar separations for intact proteins and in top-down
proteomics.
PMID- 28406608
TI - Functionalized Carbon Nanotube and Graphene Oxide Embedded Electrically
Conductive Hydrogel Synergistically Stimulates Nerve Cell Differentiation.
AB - Nerve regeneration after injury is a critical medical issue. In previous work, we
have developed an oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel
incorporated with positive charges as a promising nerve conduit. In this study,
we introduced cross-linkable bonds to graphene oxide and carbon nanotube to
obtain the functionalized graphene oxide acrylate (GOa) and carbon nanotube
poly(ethylene glycol) acrylate (CNTpega). An electrically conductive hydrogel was
then fabricated by covalently embedding GOa and CNTpega within OPF hydrogel
through chemical cross-linking followed by in situ reduction of GOa in l-ascorbic
acid solution. Positive charges were incorporated by 2
(methacryloyloxy)ethyltrimethylammonium chloride (MTAC) to obtain rGOaCNTpega-OPF
MTAC composite hydrogel with both surface charge and electrical conductivity. The
distribution of CNTpega and GOa in the hydrogels was substantiated by
transmission electron microscopy (TEM), and strengthened electrical
conductivities were determined. Excellent biocompatibility was demonstrated for
the carbon embedded composite hydrogels. Biological evaluation showed enhanced
proliferation and spreading of PC12 cells on the conductive hydrogels. After
induced differentiation using nerve growth factor (NGF), cells on the conductive
hydrogels were effectively stimulated to have robust neurite development as
observed by confocal microscope. A synergistic effect of electrical conductivity
and positive charges on nerve cells was also observed in this study. Using a
glass mold method, the composite hydrogel was successfully fabricated into
conductive nerve conduits with surficial positive charges. These results suggest
that rGOa-CNTpega-OPF-MTAC composite hydrogel holds great potential as conduits
for neural tissue engineering.
PMID- 28406609
TI - Top-Down Proteomics of Large Proteins up to 223 kDa Enabled by Serial Size
Exclusion Chromatography Strategy.
AB - Mass spectrometry (MS)-based top-down proteomics is a powerful method for the
comprehensive analysis of proteoforms that arise from genetic variations and post
translational modifications (PTMs). However, top-down MS analysis of high
molecular weight (MW) proteins remains challenging mainly due to the exponential
decay of signal-to-noise ratio with increasing MW. Size exclusion chromatography
(SEC) is a favored method for size-based separation of biomacromolecules but
typically suffers from low resolution. Herein, we developed a serial size
exclusion chromatography (sSEC) strategy to enable high-resolution size-based
fractionation of intact proteins (10-223 kDa) from complex protein mixtures. The
sSEC fractions could be further separated by reverse phase chromatography (RPC)
coupled online with high-resolution MS. We have shown that two-dimensional (2D)
sSEC-RPC allowed for the identification of 4044 more unique proteoforms and a 15
fold increase in the detection of proteins above 60 kDa, compared to one
dimensional (1D) RPC. Notably, effective sSEC-RPC separation of proteins
significantly enhanced the detection of high MW proteins up to 223 kDa and also
revealed low abundance proteoforms that are post-translationally modified. This
sSEC method is MS-friendly, robust, and reproducible and, thus, can be applied to
both high-efficiency protein purification and large-scale proteomics analysis of
cell or tissue lysate for enhanced proteome coverage, particularly for low
abundance and high MW proteoforms.
PMID- 28406610
TI - Advanced Absorption Correction for 3D Elemental Images Applied to the Analysis of
Pearl Millet Seeds Obtained with a Laboratory Confocal Micro X-ray Fluorescence
Spectrometer.
AB - We present a novel absorption correction approach for elemental distribution
images obtained with a laboratory confocal micro X-ray fluorescence spectrometer.
The procedure is suited especially for biological samples, as a constant dark
matrix with a varying minor or trace element distribution is assumed. The
constant absorption in the sample is extracted from depth dependent measurements.
By using the concept of an effective excitation energy, depth-dependent, and
element-specific excitation energy values are calculated. For each voxel of a
full 3D measurement, a correction is performed taking into account the actual
number of voxels in the excitation and detection path. As proof of concept, the
embryonic region of pearl millet seeds is investigated. Data are measured from
the top and bottom side, resulting in a good agreement after the application of
the absorption correction procedure. The distribution of elemental micronutrients
is compared in seeds of two pearl millet genotypes. The corrected images
illustrate different localization patterns of the micronutrient elements in pearl
millet seed tissues.
PMID- 28406611
TI - Evaluation of p-(13C,15N-Cyano)phenylalanine as an Extended Time Scale 2D IR
Probe of Proteins.
AB - Two-dimensional infrared (2D IR) spectroscopy provides a powerful approach for
the direct study of molecular dynamics with high spatial and temporal resolution.
Its application for investigating specific locations in proteins requires the
incorporation of IR probe groups with spectrally isolated absorptions to avoid
the congestion inherent to protein spectra. This has motivated extensive efforts
toward the development of new IR probes, but there remains a need for those that
can extend the experimental time range, which is limited by their vibrational
lifetimes. Toward this goal, isotopically labeled p-(13C15N-cyano)phenylalanine
was synthesized, site-selectively incorporated into the protein plastocyanin, and
evaluated for its potential as a 2D IR probe. The isotopic labeling increases the
vibrational lifetime about 2-fold, which results in larger signals at longer time
scales. However, isotopic labeling simultaneously shifts the absorption to a
spectral region with greater water absorbance, which results in greater heating
induced signals in the background that overlap those of the nitrile probe. The
study demonstrates the use of a new 2D IR probe to measure the side chain
dynamics in a protein and also illustrates the multiple factors to consider in
development of 2D IR probes for studying proteins.
PMID- 28406612
TI - Sulfonic Groups Originated Dual-Functional Interlayer for High Performance
Lithium-Sulfur Battery.
AB - The lithium-sulfur battery is one of the most prospective chemistries in
secondary energy storage field due to its high energy density and high
theoretical capacity. However, the dissolution of polysulfides in liquid
electrolytes causes the shuttle effect, and the rapid decay of lithium sulfur
battery has greatly hindered its practical application. Herein, combination of
sulfonated reduced graphene oxide (SRGO) interlayer on the separator is adopted
to suppress the shuttle effect. We speculate that this SRGO layer plays two
roles: physically blocking the migration of polysulfide as ion selective layer
and anchoring lithium polysulfide by the electronegative sulfonic group. Lewis
acid-base theory and density functional theory (DFT) calculations indicate that
sulfonic groups have a strong tendency to interact with lithium ions in the
lithium polysulfide. Hence, the synergic effect involved by the sulfonic group
contributes to the enhancement of the battery performance. Furthermore, the
uniformly distributed sulfonic groups working as active sites which could induce
the uniform distribution of sulfur, alleviating the excessive growth of sulfur
and enhancing the utilization of active sulfur. With this interlayer, the
prototype battery exhibits a high reversible discharge capacity of more than 1300
mAh g-1 and good capacity retention of 802 mAh g-1 after 250 cycles at 0.5 C
rate. After 60 cycles at different rates from 0.2 to 4 C, the cell with this
functional separator still recovered a high specific capacity of 1100 mAh g-1 at
0.2 C. The results demonstrate a promising interlayer design toward high
performance lithium-sulfur battery with longer cycling life, high specific
capacity, and rate capability.
PMID- 28406613
TI - Massive Parallel Analysis of Single Cells in an Integrated Microfluidic Platform.
AB - New tools that facilitate the study of cell-to-cell variability could help
uncover novel cellular regulation mechanisms. We present an integrated
microfluidic platform to analyze a large number of single cells in parallel. To
isolate and analyze thousands of individual cells in multiplexed conditions, our
platform incorporates arrays of microwells (7 pL each) in a multilayered
microfluidic device. The device allows the simultaneous loading of cells into 16
separate chambers, each containing 4640 microwells, for a total of 74 240 wells
per device. We characterized different parameters important for the operation of
the microfluidic device including flow rate, solution exchange rate in a
microchamber, shear stress, and time to fill up a single microwell with molecules
of different molecular weight. In general, after ~7.5 min of cell loading our
device has an 80% microwell occupancy with 1-4 cells, of which 36% of wells
contained a single cell. To test the functionality of our device, we carried out
a cell viability assay with adherent and nonadherent cells. We also studied the
production of neutrophil extracellular traps (NETs) from single neutrophils
isolated from peripheral blood, observing the existence of temporal heterogeneity
in NETs production, perhaps having implications in the type of the neutrophil
response to an infection or inflammation. We foresee our platform will have a
variety of applications in drug discovery and cellular biology by facilitating
the characterization of phenotypic differences in a monoclonal cell population.
PMID- 28406614
TI - Vinyluridine as a Versatile Chemoselective Handle for the Post-transcriptional
Chemical Functionalization of RNA.
AB - The development of modular and efficient methods to functionalize RNA with
biophysical probes is very important in advancing the understanding of the
structural and functional relevance of RNA in various cellular events. Herein, we
demonstrate a two-step bioorthogonal chemical functionalization approach for the
conjugation of multiple probes onto RNA transcripts using a 5-vinyl-modified
uridine nucleotide analog (VUTP). VUTP, containing a structurally noninvasive and
versatile chemoselective handle, was efficiently incorporated into RNA
transcripts by in vitro transcription reactions. Furthermore, we show for the
first time the use of a palladium-mediated oxidative Heck reaction in
functionalizing RNA with fluorogenic probes by reacting vinyl-labeled RNA
transcripts with appropriate boronic acid substrates. The vinyl label also
permitted the post-transcriptional functionalization of RNA by a reagent-free
inverse electron demand Diels-Alder (IEDDA) reaction in the presence of tetrazine
substrates. Collectively, our results demonstrate that the incorporation of VUTP
provides newer possibilities for the modular functionalization of RNA with
variety of reporters.
PMID- 28406615
TI - Redox-Sensitive MarR Homologue BifR from Burkholderia thailandensis Regulates
Biofilm Formation.
AB - Biofilm formation by pathogenic Burkholderia species is a serious complication as
it renders the bacteria resistant to antibiotics and host defenses. Using B.
thailandensis, we report here a novel redox-sensitive member of the multiple
antibiotic resistance regulator (MarR) protein family, BifR, which represses
biofilm formation. BifR is encoded as part of the emrB-bifR operon; emrB-bifR is
divergent to ecsC, which encodes a putative LasA protease. In Pseudomonas
aeruginosa, LasA has been implicated in virulence by contributing to cleavage of
elastase. BifR repressed the expression of ecsC and emrB-bifR, and expression was
further repressed under oxidizing conditions. BifR bound two sites in the
intergenic region between ecsC and emrB-bifR with nanomolar affinity under both
reducing and oxidizing conditions; however, oxidized BifR formed a disulfide
linked dimer-of-dimers, a covalent linkage that was absent in BifR-C104A in which
the redox-active cysteine was replaced with alanine. BifR also repressed an
operon encoding enzymes required for synthesis of phenazine antibiotics, which
function as alternate respiratory electron receptors, and inactivation of bifR
resulted in enhanced biofilm formation. Taken together, our data suggest that
BifR functions to control LasA production and expression of genes involved in
biofilm formation, in part by regulating synthesis of alternate electron
acceptors that promote survival in the oxygen-limiting environment of a biofilm.
The correlation between increased repression of emrB-bifR under oxidative
conditions and the formation of a covalently linked BifR dimer-of-dimers suggests
that BifR may modulate gene activity in response to cellular redox state.
PMID- 28406617
TI - The Role of Structural and Compositional Heterogeneities in the Insulator-to
Metal Transition in Hole-Doped APd3O4 (A = Ca, Sr).
AB - The cubic semiconducting compounds APd3O4 (A = Ca, Sr) can be hole-doped by Na
substitution on the A site and driven toward more conducting states. This process
has been followed here by a number of experimental techniques to understand the
evolution of electronic properties. While an insulator-to-metal transition is
observed in Ca1-xNaxPd3O4 for x >= 0.15, bulk metallic behavior is not observed
for Sr1-xNaxPd3O4 up to x = 0.20. Given the very similar crystal and (calculated)
electronic structures of the two materials, the distinct behavior is a matter of
interest. We present evidence of local disorder in the A = Sr materials through
the analysis of the neutron pair distribution function, which is potentially at
the heart of the distinct behavior. Solid-state 23Na nuclear magnetic resonance
studies additionally suggest a percolative insulator-to-metal transition
mechanism, wherein presumably small regions with a signal resembling metallic
NaPd3O4 form almost immediately upon Na substitution, and this signal grows
monotonically with substitution. Some signatures of increased local disorder and
a propensity for Na clustering are seen in the A = Sr compounds.
PMID- 28406616
TI - Inhibition of Huntingtin Exon-1 Aggregation by the Molecular Tweezer CLR01.
AB - Huntington's disease is a neurodegenerative disorder associated with the
expansion of the polyglutamine tract in the exon-1 domain of the huntingtin
protein (htte1). Above a threshold of 37 glutamine residues, htte1 starts to
aggregate in a nucleation-dependent manner. A 17-residue N-terminal fragment of
htte1 (N17) has been suggested to play a crucial role in modulating the
aggregation propensity and toxicity of htte1. Here we identify N17 as a potential
target for novel therapeutic intervention using the molecular tweezer CLR01. A
combination of biochemical experiments and computer simulations shows that
binding of CLR01 induces structural rearrangements within the htte1 monomer and
inhibits htte1 aggregation, underpinning the key role of N17 in modulating htte1
toxicity.
PMID- 28406618
TI - Microwave-Mediated Synthesis of Bulky Lanthanide Porphyrin-Phthalocyanine Triple
Deckers: Electrochemical and Magnetic Properties.
AB - Five heteroleptic lanthanide porphyrin-bis-phthalocyanine triple-decker complexes
with bulky peripheral groups were prepared via microwave-assisted synthesis and
characterized in terms of their spectroscopic, electrochemical, and magnetic
properties. These compounds, which were easily obtained under our preparative
conditions, would normally not be accessible in large quantities using
conventional synthetic methods, as a result of the low yield resulting from
steric congestion of bulky groups on the periphery of the phthalocyanine and
porphyrin ligands. The electrochemically investigated triple-decker derivatives
undergo four reversible one-electron oxidations and three reversible one-electron
reductions. The sites of oxidation and reduction were assigned on the basis of
redox potentials and UV-vis spectral changes during electron-transfer processes
monitored by thin-layer spectroelectrochemistry, in conjunction with assignments
of electronic absorption bands of the neutral compounds. Magnetic susceptibility
measurements on two derivatives containing TbIII and DyIII metal ions reveal the
presence of ferromagnetic interactions, probably resulting from magnetic dipolar
interactions. The TbIII derivative shows SMM behavior under an applied field of
0.1 T, where the direct and Orbach process can be determined, resulting in an
energy barrier of Ueff = 132.0 K. However, Cole-Cole plots reveal the presence of
two relaxation processes, the second of which takes place at higher frequencies,
with the data conforming to a 1/t ? T7 relation, thus suggesting that it can be
assigned to a Raman process. Attempts were made to form two-dimensional (2D) self
assembled networks on a highly oriented pyrolytic graphite (HOPG) surface but
were unsuccessful due to bulky peripheral groups on the two Pc macrocycles.
PMID- 28406619
TI - Interaction between Dissolved Organic Matter and Long-Chain Ionic Liquids: A
Microstructural and Spectroscopic Correlation Study.
AB - The production and use of ionic liquids (ILs) increase the potential risk after
their emission into the environment. After entering the environment, ILs will
readily interact with dissolved organic matter (DOM), and their environmental
behavior will be impacted by DOM, which is abundant in the environment and has
various functional groups. However, to date, the interaction between DOM and ILs,
especially long-chain ILs, remains unclear. In this work, the interaction between
long-chain ILs and humic acid (HA), a representative DOM, was investigated using
synchronous fluorescence, Fourier transform infrared spectroscopy, dynamic light
scattering, and zeta potential techniques, which were integrated with two
dimensional correlation spectroscopy (2DCOS), hetero-2DCOS, and perturbation
correlation moving-window analyses. The results show that cation exchange by the
carboxylic groups in humic-like fractions was primarily responsible for
interaction at low IL concentrations. As a result, the decrease in electrostatic
repulsion and the increase in hydrophobicity facilitated the loose aggregation of
HA. With an increase in IL concentration, the aromatic and carbonyl groups were
involved in the interaction via the pi-pi interaction and dipole-dipole
interaction, respectively, which resulted in the disruption of the intramolecular
hydrogen bond and promoted the compaction of HA under the hydrophobic effect. The
intensity transition sequence of various groups in HA was elucidated more
specifically by 2DCOS. With these results, a comprehensive view of the structural
changes of DOM in its IL-binding process was obtained, and the fate and
environmental impact of ILs could be better understood. Furthermore, the superior
potential of such an integrated approach in investigating the complex
interactions in the environment was also demonstrated.
PMID- 28406620
TI - Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes.
AB - An asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and
benzylic chlorides has been developed to prepare enantioenriched 1,1
diarylalkanes. As part of these studies, a new chiral bioxazoline ligand, 4
heptyl-BiOX (L1), was developed in order to obtain products in synthetically
useful yield and enantioselectivity. The reaction tolerates a variety of
heterocyclic coupling partners, including pyridines, pyrimidines, indoles, and
piperidines.
PMID- 28406621
TI - Discovery of Selective Phosphodiesterase 1 Inhibitors with Memory Enhancing
Properties.
AB - A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was
discovered. X-ray crystal structures of example compounds from this series in
complex with the catalytic domain of PDE1B and PDE10A were determined, allowing
optimization of PDE1B potency and PDE selectivity. Reduction of hERG affinity led
to greater than a 3000-fold selectivity for PDE1B over hERG. 6-(4-Methoxybenzyl)
9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11
tetrahydropyrido[4',3':4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one
was identified as an orally bioavailable and brain penetrating PDE1B enzyme
inhibitor with potent memory-enhancing effects in a rat model of object
recognition memory.
PMID- 28406622
TI - Nickel-Catalyzed Enantioselective Reductive Cross-Coupling of Styrenyl
Aziridines.
AB - A Ni-catalyzed reductive cross-coupling of styrenyl aziridines with aryl iodides
is reported. This reaction proceeds by a stereoconvergent mechanism and is thus
amenable to asymmetric catalysis using a chiral bioxazoline ligand for Ni. The
process allows facile access to highly enantioenriched 2-arylphenethylamines from
racemic aziridines. Multivariate analysis revealed that ligand polarizability,
among other features, influences the observed enantioselectivity, shedding light
on the success of this emerging ligand class for enantioselective Ni catalysis.
PMID- 28406623
TI - Spectroscopic Investigation of Up-Conversion Properties in Green Emitting
BaMgF4:Yb3+,Tb3+ Phosphor.
AB - In this work we have comprehensively studied the up-conversion (UC) properties of
BaMgF4:Yb3+,Tb3+ phosphor for the first time. BaMgF4:Yb3+,Tb3+ phosphors were
prepared by a simple and low cost precipitation method. To determine the
influence of dopant concentration on luminescence properties, the corresponding
UC luminescence spectra of BaMgF4:Yb3+,Tb3+ phosphors were studied under NIR
excitation. Emission spectra under NIR excitation reveal the vital role of Tb3+
concentration in spectral tuning from the blue to green region. The UC decay
curves were also studied to explore the possible energy transfer (ET) mechanisms
between Yb3+ and Tb3+. The results reported here are expected to provide an
approach for better understanding ET mechanisms in many Yb3+/Tb3+ codoped UC
phosphors. This study will be helpful in applications where precisely defined
optical transitions is an essential criterion.
PMID- 28406624
TI - Flame Retardant Chemicals in College Dormitories: Flammability Standards
Influence Dust Concentrations.
AB - Furniture flammability standards are typically met with chemical flame retardants
(FRs). FRs can migrate out of products into dust and are linked to cancer,
neurological impairment, and endocrine disruption. We collected 95 dust samples
from dormitory common areas and student rooms on two U.S. college campuses
adhering to two different furniture flammability standards: Technical Bulletin
117 (TB117) and Technical Bulletin 133 (TB133). Because TB133 requires furniture
to withstand a much-more-demanding test flame than TB117, we hypothesized that
spaces with TB133 furniture would have higher levels of FRs in dust. We found all
47 targeted FRs, including 12 polybrominated diphenyl ether (PBDE) congeners, 19
other brominated FRs, 11 phosphorus FRs (PFRs), 2 Dechlorane-Plus (DP) isomers,
and 3 hexabromocyclododecane (HBCDD) isomers in the 95 dust samples. We measured
the highest reported U.S. concentrations for a number of FRs, including BDE 209
(up to 990 000 ng/g), which may be used to meet the TB133 standard. We
prioritized 16 FRs and analyzed levels in relation to flammability standard as
well as presence and age of furniture and electronics. Adherence to TB133 was
associated with higher concentrations of BDE 209, decabromodiphenylethane
(DBDPE), DPs, and HBCDD compared to adherence to TB117 in univariate models (p <
0.05). Student dormitory rooms tended to have higher levels of some FRs compared
to common rooms, likely a result of the density of furniture and electronics. As
flammability standards are updated, it is critical to understand their impact on
exposure and health risks.
PMID- 28406625
TI - Large Positive Thermal Expansion and Small Band Gap in Double-ReO3-Type Compound
NaSbF6.
AB - Double-ReO3-type structure compound NaSbF6 undergoes a low-temperature
rhombohedral to high-temperature cubic phase between 303 and 323 K, as revealed
by temperature-dependent X-ray diffractions. Although many double-ReO3-type
fluorides exhibit either low thermal expansion or negative thermal expansion
(NTE), NaSbF6 exhibits positive thermal expansion (PTE) with a large volumetric
coefficient of thermal expansion, alphav = 62 ppm/K, in its cubic phase. Raman
spectroscopy reveals that the low-frequency transverse vibration of fluorine
atoms is stiffened in NaSbF6, compared with the typical NTE compound CaZrF6 with
the same structure. The related weak contraction associated with the polyhedral
rocking would be overcome by the notable elongation of the Na-F bond length on
heating, thus leading to the large volumetric PTE. Unlike ScF3 and CaZrF6 which
are insulators with a wide band gap, a relative small band gap of 3.76 eV was
observed in NaSbF6. The small band gap can be attributed to the hybridization
between the Sb 5s and F 2p orbitals.
PMID- 28406626
TI - Excimer-Monomer Photoluminescence Mechanochromism and Vapochromism of
Pentiptycene-Containing Cyclometalated Platinum(II) Complexes.
AB - The ability of the bulky H-shaped pentiptycene scaffold in promoting the
mechanochromic and vapochromic luminescence properties for organometallic
materials has been demonstrated with the N^C^N cyclometalated platinum(II)
complexes [X-NCNPtY], where X = Br or Pa, the substituent on the terdentate
dipyridylbenzene N^C^N ligand, and Y = Cl or Pa, the ancillary ligand, in which
Pa = pentiptycene acetylene. Intermolecular interactions between the planar NCNPt
cores are described by pi-pi and d-pi interactions with negligible PtII...PtII
bonding, corresponding to ligand-centered excimer rather than metal-metal-to
ligand charge-transfer emission, for these platinum(II) complexes in aggregates
and in the solid state. Interplay of the relative excimer-to-monomer emission
intensity in response to external force and/or vapor stimuli accounts for the
luminescence mechanochromism and vapochromism of the pentiptycene-incorporated
platinum(II) complexes [Pa-NCNPtCl], [Br-NCNPtPa], and [Pa-NCNPtPa], whereas the
pentiptycene-free counterpart [Br-NCNPtCl] undergoes little or no emission color
response. In particular, the complex [Pa-NCNPtCl] displays a distinct response to
aromatic versus nonaromatic organic vapors: namely, aromatic vapors such as
benzene convert the excimer emission to monomer emission, but the opposite is
true with nonaromatic vapors. A two-stage emission color change from red to
orange and then to yellow could thus be achieved by grinding and by subsequent
benzene-vapor fuming. Another feature associated with [Pa-NCNPtCl] is an
aggregation-induced green -> magenta luminescence color change in
water/tetrahydrofuran mixed solutions. The structure-luminescence property
relationship is discussed in relation to intermolecular interactions and packing
modes that depend on the number and positions of pentiptycene groups.
PMID- 28406627
TI - Diindolylmethane Derivatives: Potent Agonists of the Immunostimulatory Orphan G
Protein-Coupled Receptor GPR84.
AB - The Gi protein-coupled receptor GPR84, which is activated by (hydroxy)fatty
acids, is highly expressed on immune cells. Recently, 3,3'-diindolylmethane was
identified as a heterocyclic, nonlipid-like GPR84 agonist. We synthesized a broad
range of diindolylmethane derivatives by condensation of indoles with
formaldehyde in water under microwave irradiation. The products were evaluated at
the human GPR84 in cAMP and beta-arrestin assays. Structure-activity
relationships (SARs) were steep. 3,3'-Diindolylmethanes bearing small lipophilic
residues at the 5- and/or 7-position of the indole rings displayed the highest
activity in cAMP assays, the most potent agonists being di(5-fluoro-1H-indole-3
yl)methane (38, PSB-15160, EC50 80.0 nM) and di(5,7-difluoro-1H-indole-3
yl)methane (57, PSB-16671, EC50 41.3 nM). In beta-arrestin assays, SARs were
different, indicating biased agonism. The new compounds were selective versus
related fatty acid receptors and the arylhydrocarbon receptor. Selected compounds
were further investigated and found to display an ago-allosteric mechanism of
action and increased stability in comparison to the lead structure.
PMID- 28406628
TI - Ferromagnetic Exchange in Bichloride Bridged Cu(II) Chains: Magnetostructural
Correlations between Ordered and Disordered Systems.
AB - The synthesis, structure, magnetic properties, and theoretical analysis of a new
phase of dichloro(2-chloro-3-methylpyridine)copper(II) (2) and its isomorphous
analogue dichloro(2-bromo-3-methylpyridine)copper(II) (3) are reported. Both
complexes crystallize in the orthorhombic space group Pbca and present square
pyramidal Cu(II) ions bridged into chains by chloride ions with each copper(II)
bearing a single pyridine ligand. Variable temperature magnetic susceptibility
measurements were well fit by a uniform one-dimensional ferromagnetic chain model
with 2, J = 69.0(7) K, C = 0.487 emu-K/mol-Oe; 3, J = 73.9(4) K, C = 0.463 emu
K/mol-Oe (H = -JSigmaSi.Sj Hamiltonian). The experimental J-values were confirmed
via theoretical calculations. Comparison to a known disordered polymorph of
dichloro(2-chloro-3-methylpyridine)copper(II), 1, shows marked differences as
there are significant antiferromagnetic next-nearest neighbor interactions in 1
in addition to randomness induced by the disorder which provide a distinctly
different magnetic response. The differences in magnetic behavior are attributed
principally to the structural difference in the Cu(II) coordination sphere, 1
being significantly closer to trigonal-bipyramidal, whose difference changes both
the nearest and next-nearest neighbor interactions.
PMID- 28406629
TI - First Dual Inhibitors of Steroid Sulfatase (STS) and 17beta-Hydroxysteroid
Dehydrogenase Type 1 (17beta-HSD1): Designed Multiple Ligands as Novel Potential
Therapeutics for Estrogen-Dependent Diseases.
AB - STS and 17beta-HSD1 are attractive targets for the treatment of estrogen
dependent diseases like endometriosis and breast cancer. The simultaneous
inhibition of both enzymes appears more promising than blockage of either protein
alone. We describe a designed multiple ligand approach resulting in highly potent
dual inhibitors. The most interesting compound 9 showed nanomolar IC50 values for
both proteins, membrane permeability, and no interference with estrogen
receptors. It efficiently reversed E1S- and E1-induced T47D cell proliferation.
PMID- 28406630
TI - Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple
Pollutants with High Performance.
AB - Simultaneous removal of multiple pollutants from aqueous solution with less
energy consumption is crucial in water purification. Here, a novel concept of
dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of
nanostructured adsorbents into the finger-like pores of ultrafiltration (UF)
membrane rather than in the membrane matrix in previous reports of blend
membranes, resulting in an exceptionally high active content and simultaneous
removal of multiple pollutants from water due to the dual functions of rejection
and adsorption. As a demonstration, hollow porous Zr(OH)x nanospheres (HPZNs)
were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine
coating with a high content of 68.9 wt %. The decontamination capacity of DFUF
membranes toward multiple model pollutants (colloidal gold, polyethylene glycol
(PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend
membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment
volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10
ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively
removed the colloidal gold and PEG below instrument detection limit, however the
blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and
PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of
nanoadsorbents during testing; and the membrane can be easily regenerated and
reused. This study sheds new light on the design of high performance
multifunction membranes for drinking water purification.
PMID- 28406631
TI - Origin of Remarkably Different Acidity of Hydroxycoumarins-Joint Experimental and
Theoretical Studies.
AB - In the present work the origin of highly varied acidity of hydroxycoumarins (pKa
values) has been for the first time investigated by joint experimental and
computational studies. The structurally simple regio-isomers differing in the
location of hydroxyl group, 3-hydroxycoumarin (3-HC), 4-hydroxycoumarin (4-HC), 6
hydroxycoumarin (6-HC), 7-hydroxycoumarin (7-HC), as well as 4,7
dihydroxycoumarin (4,7-HC) and the larger 4-hydroxycoumarin-based derivatives:
warfarin (WAR), 7-hydroxywarfarin (W7), coumatetralyl (CT), and 10
hydroxywarfarin (W10), have been compared in terms of enthalpy-entropy
relationships accounting for the observed pKa values. We have revealed that in
the case of large molecules the acidic proton is stabilized by the following
noncovalent interactions OH...O (WAR and W7), OH...pi (CT), and OH...OH...O
(W10), this effect leads to a compensatory enthalpy-entropy relation and yields a
moderate pKa increase. On the other hand, different location of the hydroxyl
group in the regio-isomers (3-HC, 4-HC, 6-HC, and 7-HC) leads to the massive
changes in acidity due to a lack of enthalpy-entropy compensation. Our results
suggest that the solvent-solute interactions and electron delocalization degree
in anions contribute to the observed behaviors. Such knowledge can be useful in
the future to design novel systems exhibiting desired acid-base properties, and
to elucidate enthalpy-entropy compensation phenomena.
PMID- 28406632
TI - Toward the Mechanism of Perchlorinated Cyclopentasilane (Si5Cl10) Ring Flattening
in the [Si5Cl10.2Cl]2- Dianion.
AB - We report the detailed computational study of flattening of the puckered Si5 ring
by suppression of the pseudo-Jahn-Teller (PJT) effect through coordination of two
Cl- anions to the molecule forming an inverse sandwich dianion [Si5Cl10.2Cl]2-
complex. The PJT effect that causes nonplanarity of the Si5Cl10 structure (Cs)
results from vibronic coupling of pairs of occupied molecular orbitals (OMOs) and
unoccupied molecular orbitals (UMOs). It was shown that filling the intervenient
molecular orbitals of puckered Si5Cl10 with valent electron pairs of Cl- donors
suppresses the PJT effect, with the Si5 ring becoming planar (D5h) upon complex
formation. In this paper, the stabilization energy E(2) associated with donor
acceptor charge transfer (delocalization) was estimated using NBO analysis for
all studied inverse sandwich compounds [Si5Cl10.2X]2- (where X = F, Cl, Br). It
was found that the polarizability of the donor ion might significantly affect the
stabilization energy value and should be taken into account when choosing the
ligands suitable for forming Si-based one-dimensional compounds and other
nanoscale materials.
PMID- 28406634
TI - Molecular Products and Fundamentally Based Reaction Pathways in the Gas-Phase
Pyrolysis of the Lignin Model Compound p-Coumaryl Alcohol.
AB - The fractional pyrolysis of lignin model compound para-coumaryl alcohol (p-CMA)
containing a propanoid side chain and a phenolic OH group was studied using the
System for Thermal Diagnostic Studies at temperatures from 200 to 900 degrees C,
in order to gain mechanistic insight into the role of large substituents in high
lignin feedstocks pyrolysis. Phenol and its simple derivatives p-cresol, ethyl-,
propenyl-, and propyl-phenols were found to be the major products predominantly
formed at low pyrolysis temperatures (<500 degrees C). A cryogenic trapping
technique was employed combined with EPR spectroscopy to identify the open-shell
intermediates registered at pyrolysis temperatures above 500 degrees C. These
were characterized as radical mixtures primarily consisting of oxygen-linked
conjugated radicals. A comprehensive potential energy surface analysis of p-CMA
and p-CMA + H atom systems was performed using various DFT protocols to examine
the possible role of concerted molecular eliminations and free-radical mechanisms
in the formation of major products. Other significant unimolecular concerted
reactions along with formation and decomposition of primary radicals are also
described and evaluated. The calculations suggest that a set of the chemically
activated secondary radical channels is relevant to the low temperature product
formation under fractional pyrolysis conditions.
PMID- 28406633
TI - Probing the Conformationally Excited States of Membrane Proteins via 1H-Detected
MAS Solid-State NMR Spectroscopy.
AB - Proteins exist in ensembles of conformational states that interconvert on various
motional time scales. High-energy states of proteins, often referred to as
conformationally excited states, are sparsely populated and have been found to
play an essential role in many biological functions. However, detecting these
states is quite difficult for conventional structural techniques. Recent progress
in solution NMR spectroscopy made it possible to detect conformationally excited
states in soluble proteins and characterize them at high resolution. As for
soluble proteins, integral or membrane-associated proteins populate different
structural states often modulated by their lipid environment. Solid-state NMR
spectroscopy is the method of choice to study membrane proteins, as it can detect
both ground and excited states in their natural lipid environments. In this work,
we apply newly developed 1H-detected 15N-HSQC type experiments under moderate
magic angle spinning speeds to detect the conformationally excited states of
phospholamban (PLN), a single-pass cardiac membrane protein that regulates Ca2+
transport across sarcoplasmic reticulum membrane. In its unbound state, the
cytoplasmic domain of PLN exists in equilibrium between a T state, which is
membrane bound and helical, and an R state, which is membrane detached and
unfolded. The R state is important for regulation of the sarcoplasmic reticulum
Ca2+-ATPase, but also for binding to protein kinase A. By hybridizing 1H detected
solution and solid-state NMR techniques, it is possible to detect and resolve the
amide resonances of the R state of PLN in liquid crystalline lipid bilayers.
These new methods can be used to study the conformationally excited states of
membrane proteins in native-like lipid bilayers.
PMID- 28406635
TI - Interrelations Between Side Chain and Main Chain Packing in Different Crystal
Modifications of Alkoxylated Polyesters.
AB - Interrelations between main chain and side chain packing are studied in a series
of comb-like poly(1,4-phenylene-2,5-n-dialkyloxy terephthalate)s (PPAOTs) with C
= 6-12 alkyl carbons per side chain by X-ray diffractometry. Two different
polymorphic states, called modification A and modification B, are observed
depending on thermal treatment and side chain length. For PPAOTs with short side
chains (C <= 8), modification A is commonly observed. "As synthesized" (solution
crystallized) PPAOTs with longer side chains (C >= 10) contain mostly
modification B while modification A is growing during melt cooling. A solid-solid
transition from modification B to modification A is observed above ~70 degrees C
for the decyl member (C = 10, PPDOT) while modification A converts under ambient
conditions slowly to modification B. This indicates that modification B is
thermodynamically stable at low temperature while modification A is stable at
higher temperature. Crystallographic analysis shows that both modifications are
characterized by an orthorhombic unit cell and a long-range ordered layered
structure with alternating main chain and alkyl nanodomains. This is confirmed by
2D diffration data for shear oriented PPDOT fibers. The main difference between
both modifications is the packing of the side chains which are in a crystalline
state for modification B but disordered for modification A. This is concluded
from values for the volume per CH2 unit VCH2 in alkyl nanodomains calculated
without further assumptions from the obtained lattice parameters. Interestingly,
the crystalline packing of the side chains in modification B leads to a
significant increase (~ 20%) in the application relevant pi-pi spacings within
the main chain domains as compared to those for modification A. It is argued that
the structure formation process and thermodynamic equilibrium in comb-like
polymers might be strongly influenced by a competition of the individual packing
tendencies of main and side chains.
PMID- 28406636
TI - Marine Terpenoid Diacylguanidines: Structure, Synthesis, and Biological
Evaluation of Naturally Occurring Actinofide and Synthetic Analogues.
AB - A new diacylguanidine, actinofide (1), has been isolated from the marine mollusk
Actinocyclus papillatus. The structure, exhibiting a guanidine moiety acylated by
two terpenoid acid units, has been established by spectroscopic methods and
secured by synthesis. Following this, a series of structural analogues have been
synthesized using the same procedure. All of the compounds have been evaluated in
vitro for the growth inhibitory activity against a variety of cancer cell lines.
PMID- 28406637
TI - pi-Stacked Dimers of Fluorophenylacetylenes: Role of Dipole Moment.
AB - The homodimers of singly fluorine-substituted phenylacetylenes were investigated
using electronic and vibrational spectroscopic methods in combination with
density functional theory calculations. The IR spectra in the acetylenic C-H
stretching region show a marginal red shift for the dimers relative to the
monomers. Further, the marginal red shifts indicate that the acetylenic group in
all the dimers is minimally perturbed relative to the corresponding monomer. The
observed spectra were assigned to a set of pi-stacked structures within an energy
range of 1.5 kJ mol-1, which differ in the relative orientation of the two
monomers on the basis of M06-2X/aug-cc-pVTZ level calculation. The observed red
shift in the acetylenic C-H stretching vibration of the dimers suggests that the
antiparallel structures contribute predominantly based on a simple coupled dipole
model. Energy decomposition analysis using symmetry-adapted perturbation theory
indicates that dispersion plays a pivotal role in pi-pi stacking with appreciable
contribution of electrostatics. The stabilization energies of
fluorophenylacetylene dimers follow the same ordering as their dipole moments,
which suggests that dipole moment enhances the ability to form pi-stacked
structures.
PMID- 28406638
TI - Orbitals, Occupation Numbers, and Band Structure of Short One-Dimensional Cadmium
Telluride Polymers.
AB - Recent work found that soldering CdTe quantum dots together with a molecular CdTe
polymer yielded field-effect transistors with much greater electron mobility than
quantum dots alone. We present a computational study of the CdTe polymer using
the active-space variational two-electron reduced density matrix (2-RDM) method.
While analogous complete active-space self-consistent field (CASSCF) methods
scale exponentially with the number of active orbitals, the active-space
variational 2-RDM method exhibits polynomial scaling. A CASSCF calculation using
the (48o,64e) active space studied in this paper requires 1024 determinants and
is therefore intractable, while the variational 2-RDM method in the same active
space requires only 2.1 * 107 variables. Natural orbitals, natural-orbital
occupations, charge gaps, and Mulliken charges are reported as a function of
polymer length. The polymer, we find, is strongly correlated, despite possessing
a simple sp3-hybridized bonding scheme. Calculations reveal the formation of a
nearly saturated valence band as the polymer grows and a charge gap that
decreases sharply with polymer length.
PMID- 28406639
TI - Is Carbene Formation Necessary for Dissolving Cellulose in Ionic Liquids?
AB - In this work we explored through molecular dynamics simulations how the
dissolution of cellulose and its fragments in 1-ethyl-3-methylimidazolium acetate
is affected by the inherent accessibility of carbenes in this solvent. We show
that-apart from the decomposition reactions-carbenes do not interact strongly
with the solute carbohydrates, as the solute-solvent interactions are dominated
by the anion. On the other hand, the formation of the carbene is hindered by the
hydrogen bond donor hydroxyl groups at the carbohydrate through occupying the
anion, and hence disrupting the anion-cation interplay. Comparing the rate of
dissolution of a cellulose bundle in the pure IL to that in the presence of
carbenes showed that not only the cellulose hinders the carbene formation, but
the presence of carbenes also make the dissolution of the cellulose slower.
Accordingly, although based on indirect experimental findings one might speculate
otherwise, the solubility and carbene formation are merely two independent
consequences of the basicity of the ionic liquid anion, and the presence of
carbenes is not necessary for breaking up the cellulose into individual chains.
Based on these results we can conclude that it is, in principle, possible to
design an ionic liquid that is an ideal solvent for this biopolymer, which
dissolves, but does not decompose cellulose.
PMID- 28406640
TI - Cobalt-Catalyzed Intramolecular Oxidative C(sp3)-H/N-H Carbonylation of Aliphatic
Amides.
AB - A cobalt-catalyzed reaction protocol is developed to achieve the intramolecular
oxidative C(sp3)-H/N-H carbonylation of aliphatic amides with CO. Various
substituted propanamides are selectively transformed into corresponding
succinimides in good to high yields. Notably, predominant selectivity for the
carbonylation at the alpha-methyl groups of linear aliphatic amides is observed
in this reaction system.
PMID- 28406641
TI - Quenching of Single-Walled Carbon Nanotube Fluorescence by Dissolved Oxygen
Reveals Selective Single-Stranded DNA Affinities.
AB - The selective interactions between short oligomers of single-stranded DNA (ssDNA)
and specific structures of single-walled carbon nanotubes have been exploited in
powerful methods for nanotube sorting. We report here that nanotubes coated with
ssDNA also display selective interactions through the selective quenching of
nanotube fluorescence by dissolved oxygen. In aqueous solutions equilibrated
under 1 atm of O2, emission intensity from semiconducting nanotubes is reduced by
between 9 and 40%, varying with the combination of ssDNA sequence and nanotube
structure. This quenching reverses promptly and completely on the removal of
dissolved O2 and may be due to physisorption on nanotube surfaces. Fluorescence
quenching offers a simple, nondestructive approach for studying the structure
selective interactions of ssDNA with single-walled carbon nanotubes and
identifying recognition sequences.
PMID- 28406642
TI - Impact of Halogenido Coligands on Magnetic Anisotropy in Seven-Coordinate Co(II)
Complexes.
AB - The structural and magnetic features of a series of mononuclear seven-coordinate
CoII complexes with the general formula [Co(L)X2], where L is a 15-membered
pyridine-based macrocyclic ligand (3,12,18-triaza-6,9
dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene) and X = Cl- (1), Br- (2), or I-
(3), were investigated experimentally and theoretically in order to reveal how
the corresponding halogenido coligands in the apical positions of a distorted
pentagonal-bipyramidal coordination polyhedron may affect the magnetic properties
of the prepared compounds. The thorough analyses of the magnetic data revealed a
large easy-plane type of the magnetic anisotropy (D > 0) for all three compounds,
with the D-values increasing in the order 35 cm-1 for 3 (I-), 38 cm-1 for 1 (Cl
), and 41 cm-1 for 2 (Br-). Various theoretical methods like the Angular Overlap
Model, density functional theory, CASSCF/CASPT2, CASSCF/NEVPT2 were utilized in
order to understand the observed trend in magnetic anisotropy. The D-values
correlated well with the Mayer bond order (decreasing in order Co-I > Co-Cl > Co
Br), which could be a consequence of two competing factors: (a) the ligand field
splitting and (b) the covalence of the Co-X bond. All the complexes also behave
as field-induced single-molecule magnets with the spin reversal barrier Ueff
increasing in order 1 (Cl-) < 2 (Br-) < 3 (I-); however, taking into account the
easy-plane type of the magnetic anisotropy, the Raman relaxation process is most
likely responsible for slow relaxation of the magnetization. The results of the
work revealed that the previously suggested and fully accepted strategy employing
heavier halogenido ligands in order to increase the magnetic anisotropy has some
limitations in the case of pentagonal-bipyramidal CoII complexes.
PMID- 28406643
TI - Polyketides and Anthranilic Acid Possessing 6-Deoxy-alpha-l-talopyranose from a
Streptomyces Species.
AB - A bioassay-guided investigation in conjunction with chemical screening led to the
isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy
alpha-l-talopyranoside (2), and naphthomycinoside (3), along with three known
secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures
were elucidated by detailed NMR and MS spectroscopic analyses. Absolute
configurational analysis of the sugar units based on the magnitudes of the
coupling constants, NOESY correlations, chemical derivatization, and optical
rotation measurements revealed that compounds 1-3 and 5 incorporate the rare
deoxyhexose 6-deoxy-alpha-l-talopyranose. The absolute configuration of a
polyketide extender unit of 3 was determined by applying the J-based
configuration analysis and modified Mosher's method. Ulleungoside (1) and
naphthomycin A (7) showed in vitro inhibitory effects against indoleamine 2,3
dioxygenase activity. Further bioevaluation revealed that compounds 1 and 7 had
moderate antiproliferative activities against several cancer cell lines, and
compounds 5 and 6, which are members of the piericidin family, induced
autophagosome accumulation.
PMID- 28406645
TI - A General Approach to Quaternary Center Construction from Couplings of
Unactivated Alkenes and Acyl Xanthates.
AB - A general, radical-mediated approach to quaternary center construction using
unactivated alkenes as coupling partners is reported. In this strategy, acyl
xanthates, readily accessed from carboxylic acids, serve as precursors to
tertiary radicals. This strategy leverages the unique reactivity of xanthates to
participate in efficient radical-mediated additions to unactivated alkenes,
expanding the scope of quaternary center construction.
PMID- 28406644
TI - Influence of the Steric Bulk and Solvent on the Photoreactivity of Ruthenium
Polypyridyl Complexes Coordinated to l-Proline.
AB - Ruthenium polypyridyl complexes are good candidates for photoactivated
chemotherapy (PACT) provided that they are stable in the dark but efficiently
photosubstitute one of their ligands. Here the use of the natural amino acid l
proline as a protecting ligand for ruthenium-based PACT compounds is investigated
in the series of complexes Lambda-[Ru(bpy)2(l-prol)]PF6 ([1a]PF6; bpy = 2,2'
bipyridine and l-prol = l-proline), Lambda-[Ru(bpy)(dmbpy)(l-prol)]PF6 ([2a]PF6
and [2b]PF6; dmbpy = 6,6'-dimethyl-2,2'-bipyridine), and Lambda-[Ru(dmbpy)2(l
prol)]PF6 ([3a]PF6). The synthesis of the tris-heteroleptic complex bearing the
dissymmetric proline ligand yielded only two of the four possible regioisomers,
called [2a]PF6 and [2b]PF6. Both isomers were isolated and characterized by a
combination of spectroscopy and density functional theory calculations. The
photoreactivity of all four complexes [1a]PF6, [2a]PF6, [2b]PF6, and [3a]PF6 was
studied in water (H2O) and acetonitrile (MeCN) using UV-vis spectroscopy,
circular dichroism spectroscopy, mass spectrometry, and 1H NMR spectroscopy. In
H2O, upon visible-light irradiation in the presence of oxygen, no
photosubstitution took place, but the amine of complex [1a]PF6 was photooxidized
to an imine. Contrary to expectations, enhancing the steric strain by the
addition of two ([2b]PF6) or four ([3a]PF6) methyl substituents did not lead, in
phosphate-buffered saline (PBS), to ligand photosubstitution. However, it
prevented photoxidation, probably as a consequence of the electron-donating
effect of the methyl substituents. In addition, whereas [2b]PF6 was photostable
in PBS, [2a]PF6 quantitatively isomerized to [2b]PF6 upon light irradiation. In
pure MeCN, [2a]PF6 and [3a]PF6 showed non-selective photosubstitution of both the
l-proline and dmbpy ligands, whereas the non-strained complex [1a]PF6 was
photostable. Finally, in H2O-MeCN mixtures, [3a]PF6 showed selective
photosubstitution of l-proline, thus demonstrating the active role played by the
solvent on the photoreactivity of this series of complexes. The role of the
solvent polarity and coordination properties on the photochemical properties of
polypyridyl complexes is discussed.
PMID- 28406647
TI - Stereopure Functionalized Benzosultams via Ruthenium(II)-Catalyzed Dynamic
Kinetic Resolution-Asymmetric Transfer Hydrogenation.
AB - A highly diastereo- and enantioselective Ru(II)-catalyzed dynamic kinetic
resolution-asymmetric transfer hydrogenation (DKR-ATH) of alpha-(N-sulfonylimino)
and alpha-(N-sulfonylamino) aryl ketones to 4-hydroxy-benzo-delta- and 3-(alpha
hydroxy-arylmethyl)-benzo-gamma-sultams is presented. By employing enantiopure
ansa-Ru[PipSO2DPEN(CH2)4Ph] cat. II with S/C = 10 000 in a HCO2H/Et3N binary mix,
up to >99.9% ee and dr >99:1 are obtained with 100% conversion under mild
conditions. Application to access the stereopure "structurally simplified TsDPEN"
N,N-ligand syn-3-(alpha-aminobenzyl)-benzo-gamma-sultam ("syn-ULTAM") and its
structural isomer trans-4-amino-3-phenyl-benzo-delta-sultam (trans-4) is
demonstrated.
PMID- 28406646
TI - Transforming Sphingosine Kinase 1 Inhibitors into Dual and Sphingosine Kinase 2
Selective Inhibitors: Design, Synthesis, and in Vivo Activity.
AB - Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts
with its five G-protein coupled receptors (S1P1-5) to regulate cell growth and
survival and has been implicated in a variety of diseases including cancer and
sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine
kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for
pharmaceutical inhibition. In this article, we describe the design, synthesis,
and biological evaluation of aminothiazole-based guanidine inhibitors of SphK.
Surprisingly, combining features of reported SphK1 inhibitors generated SphK1/2
dual inhibitor 20l (SLC4011540) (hSphK1 Ki = 120 nM, hSphK2 Ki = 90 nM) and SphK2
inhibitor 20dd (SLC4101431) (Ki = 90 nM, 100-fold SphK2 selectivity). These
compounds effectively decrease S1P levels in vitro. In vivo administration of
20dd validated that inhibition of SphK2 increases blood S1P levels.
PMID- 28406648
TI - Mechanisms of change in cognitive therapy for major depressive disorder in the
community mental health setting.
AB - OBJECTIVE: This study examined the relation of change in theory-relevant
cognitive variables to depressive symptom change over the course of cognitive
therapy, as well as the specificity of change mechanisms to cognitive therapy as
compared with dynamic therapy. METHOD: There were 237 adult outpatients who were
randomized to either cognitive (n = 119) or dynamic (n = 118) therapy for major
depressive disorder in a community mental health setting. Assessments of
compensatory skills (Ways of Responding Community Version and Self-Report
Version), dysfunctional attitudes (Dysfunctional Attitudes Scale), and
depressogenic schemas (Psychological Distance Scaling Task) were obtained at
baseline and months 1, 2, and 5 following baseline. Primary outcome was measured
using the Hamilton Rating Scale for Depression. RESULTS: Across both therapy
conditions, change in all 3 cognitive domains was associated with concurrent
change in depressive symptoms. After controlling for other cognitive variables,
increased interconnectedness of the positive achievement-related schema was
significantly associated with concurrent symptom change in cognitive (rp = .26, p
< .001) but not dynamic therapy (rp = .08, p = .29). Increases in positive
compensatory skills were associated with subsequent change in depressive symptoms
in cognitive therapy (rp = -.36, p = .003), but not in dynamic therapy (rp = .11,
p = .386). CONCLUSIONS: Results provide support for the compensatory skills model
of cognitive therapy (CT) within a community mental health setting. Additional
research is necessary to understand other possible mechanisms of change in CT in
the community setting. (PsycINFO Database Record
PMID- 28406649
TI - Born this way: Sexual orientation beliefs and their correlates in lesbian and
bisexual women.
AB - In this study, we examined how beliefs about the nature and origin of sexual
orientation were associated with sexual identity outcomes, namely internalized
sexual stigma and sexual orientation uncertainty, and in turn, psychological well
being in sexual minority women. A community sample of 393 lesbian and 205
bisexual women were recruited for a cross-sectional online survey. Using
multigroup structural equation modeling, we examined whether believing sexual
orientation to be inborn/immutable (i.e., natural) and/or as existing in discrete
categories (i.e., discrete) was indirectly associated with psychological well
being via internalized stigma and sexual orientation uncertainty and whether some
of these relationships were moderated by nonprototypical attractions
(nonexclusive same-sex attractions in lesbian women and straight- or lesbian
leaning attractions in bisexual women) and age. Overall, similar patterns of
direct effects were observed in lesbian and bisexual women. In both groups,
naturalness beliefs were associated with lower internalized-stigma, whereas
discreteness beliefs were associated with greater internalized stigma. In
bisexual women, nonprototypical sexual attraction patterns moderated the
relationship between discreteness beliefs and sexual orientation uncertainty.
Younger age was associated with increased sexual orientation uncertainty in both
lesbian and bisexual women. Specific to lesbian women, nonprototypical attraction
predicted less endorsement of immutability and binary/discrete beliefs about
sexual orientation, and unexpectedly, greater internalized stigma. The present
study identifies potential implications of common lay theories of sexual
orientation for lesbian versus bisexual women. (PsycINFO Database Record
PMID- 28406650
TI - Disability identity development: A systematic review of the literature.
AB - PURPOSE/OBJECTIVE: The purpose of this systematic review was to synthesize
existing empirical research on disability identity development. This review is
organized to present the demographics of participants and types of disabilities
represented in the existing data, measures of disability identity development and
theoretical models of disability identity development. METHOD: Electronic
databases (EBSCO, PsycINFO, ERIC, and Sociological Abstracts) were searched for
all peer reviewed empirical studies published between 1980 and 2017. Articles
were excluded if they were theoretical and/or did not include participants with
disabilities, or focused on a disability-specific community identity rather than
general disability identity. RESULTS: Empirical articles (N = 41) were included
in the final review. An overwhelming majority (75.6%) were qualitative in nature,
with only 22% of the articles reviewed being quantitative and only 1 that
utilized a mixed methods design. The results suggest that disability identity can
be considered a unique phenomenon that shapes persons' ways of seeing themselves,
their bodies, and their way of interacting with the world.
CONCLUSIONS/IMPLICATIONS: Disability identity development has the potential to
become an important factor in developing effective interventions and/or
therapies. Identity development is a fundamentally social process, and identities
are formed through mirroring, modeling, and recognition through available
identity resources, and so it is imperative that able-bodied professionals (i.e.,
rehabilitation professionals, therapists, teachers and caregivers) working with
individuals with disabilities become aware of this developmental process to be
able to better support individuals along this journey. (PsycINFO Database Record
PMID- 28406651
TI - Perceived social support moderates the relationship between activities of daily
living and depression after lower limb loss.
AB - OBJECTIVE: This study examined the moderating influence of perceived social
support on the prospective relationship between baseline levels of activities of
daily living (ADL) and depressive symptoms during the 1st year following
amputation. METHOD: Participants included 73 veterans with new/first unilateral
lower extremity amputation due to vascular disease or diabetes. Baseline levels
of perceived social support, ADL function, and mobility were assessed by
retrospective recall 6 weeks after amputation. Depressive symptoms were measured
at 6 weeks and 12 months following surgery. RESULTS: Perceived social support
moderated the relationship between baseline ADL functioning and depressive
symptoms at 12 months (beta = -0.27, p < .001) after controlling for 6-week
depressive symptoms and sociodemographic and physical/functional variables. Lower
levels of baseline ADL function were associated with depressive symptoms at 12
months among those who reported lower levels of perceived social support.
CONCLUSION: These data allowed us to identify those participants with both low
ADL function at baseline and low social support as being at higher risk for
depression symptoms postamputation. The findings support the stress buffering
hypothesis and suggest that perceived social support may be an important
modifiable target of intervention among individuals with lower levels of
functioning. (PsycINFO Database Record
PMID- 28406652
TI - Family functioning and child asthma severity: A bio-behavioral approach.
AB - INTRODUCTION: Family factors are directly associated with the psychosocial
adjustment of children with chronic illnesses such as asthma (Kaugars, Klinnert,
& Bender, 2004). Research indicates that negative family factors may also
contribute to child disease severity via bio-behavioral mechanisms of effect. For
instance, children from more conflicted families often experience greater
internalizing symptoms that subsequently impact their asthma severity (Wood et
al., 2006). These pathways have yet to be examined with a comprehensive focus on
strength-based family factors. This study examined whether factors such as family
cohesion, problem-solving abilities, and communication influence asthma severity
via their effects on child depression and anxiety symptoms. METHOD: Participants
were 215 children (136 males and 79 females), ages 5 to 12 years old, and their
families. Primary caregiver, child, and teacher ratings of child and family
functioning in addition to objective measures of parent-child interactions and
asthma severity were collected. RESULTS: Using structural equation modeling, the
authors identified significant indirect associations between family factors and
child asthma severity via child depressive symptoms; however, these associations
were not present in models with child anxiety symptoms. DISCUSSION: Results
suggest an indirect effect of family functioning on children's lung function,
with differential roles of anxiety and depression in these pathways. This article
also highlights the importance of incorporating multirater multimethod measures
to understand children's experiences in pediatric asthma. (PsycINFO Database
Record
PMID- 28406654
TI - Communication moderates effects of residential mobility on relationship quality
among ethnically diverse couples.
AB - Although interpersonal communication is a defining feature of committed
relationships, the quality of couple communication has not proven to be a
straightforward cause of relationship quality. At the same time, emerging models
argue that external circumstances likely combine with communication to generate
changes in relationship quality. We integrate these 2 ideas by proposing that
communication does exert effects on changes in relationship quality, but
primarily when couples encounter challenging situations that require an adaptive
response. In the present study we examine residential moves to different
neighborhoods as one such adaptive challenge. We conducted a longitudinal study
of 414 newlywed couples to examine whether observed communication moderates the
effect of moving to higher- or lower-income neighborhoods on changes in
relationship quality. Results indicate that communication exerts no main effects
on relationship quality. Consistent with the proposed model, however, wives who
displayed less positive, less effective, and more negative behaviors experienced
greater decreases in relationship quality, but only when couples moved to
substantially higher-income neighborhoods. Because communication may not affect
relationship quality until couples encounter qualitatively new demands,
strengthening relationships may pivot less on improving communication skills and
more on ensuring that couples' circumstances do not overwhelm the skills that
they already possess. (PsycINFO Database Record
PMID- 28406655
TI - Heterogeneity in externalizing problems at age 3: Association with age 15
biological and environmental outcomes.
AB - Investigating heterogeneity in antisocial behavior early in life is essential for
understanding the etiology, development, prognosis, and treatment of these
problems. Data from the longitudinal National Institute of Child Health and
Development (NICHD) study of Early Child Care were used to identify homogeneous
groups of young antisocial children differentiated on externalizing problems,
internalizing problems, and callous-unemotional (CU) traits using latent profile
analysis (LPA). We examined how identified subgroups were differentiated on
adolescent social, biological, cognitive, and environmental outcomes, controlling
for dispositional and contextual antecedents during the first 2 years of life.
The sample consisted of 1,167 children (52% male) followed from toddlerhood to
adolescence. LPA identified a large "low problems" group (n = 795; 49.9% male) as
well as 3 antisocial groups at age 3: the first scored high on internalizing and
externalizing problems but low on CU traits (Ext/Int, n = 125), the second scored
high on CU traits and externalizing problems but low on internalizing problems
(primary CU variant, n = 135), and the third scored high on CU traits,
internalizing, and externalizing problems (secondary CU variant, n = 112), and
these differences persisted into adolescence. Primary and secondary CU variants
were further differentiated from one another on adolescent measures of aggression
(reactive and relational), biological indices (cortisol, heart rate), cognitive
abilities, and parental psychopathology, after controlling for early life risk
factors (i.e., maternal sensitivity, difficult temperament, and maternal
depression). We discuss implications of our findings for research, theory, and
practice on early childhood externalizing problems. (PsycINFO Database Record
PMID- 28406653
TI - Aging and the optimal viewing position effect in visual word recognition:
Evidence from English.
AB - Words are recognized most efficiently by young adults when fixated at an optimal
viewing position (OVP), which for English is between a word's beginning and
middle letters. How this OVP effect changes with age is unknown but may differ
for older adults due to visual declines in later life. Accordingly, a lexical
decision experiment was conducted in which short (5-letter) and long (9-letter)
words were fixated at various letter positions. The older adults produced slower
responses. But, crucially, effects of fixation location for each word-length did
not differ substantially across age groups, indicating that OVP effects are
preserved in older age. (PsycINFO Database Record
PMID- 28406656
TI - Is pre-K classroom quality associated with kindergarten and middle-school
academic skills?
AB - We employed data from a longitudinal investigation of over 1,000 children who
participated in Tulsa's universal school-based pre-K program in 2005, and path
modeling techniques, to examine the contribution of pre-K classroom quality to
both kindergarten- and middle-school academic skills. We also examined gender and
income-related differences in quality-outcome associations. Both Instructional
and Emotional Support in pre-K classrooms, but not Classroom Management, assessed
with the Classroom Assessment Scoring System (CLASS), were associated with
kindergarten academic skills and, modestly indirectly associated through these
immediate impacts, to middle-school test scores. Linear associations were found
for Instructional Support whereas nonlinear patterns of association were evident
for Emotional Support. Gender and income differences characterized Instructional
Support-outcome associations. Results are discussed in terms of implications for
improving pre-K quality as one avenue for supporting the ongoing development of
academic skills. (PsycINFO Database Record
PMID- 28406657
TI - Using latent variable- and person-centered approaches to examine the role of
psychopathic traits in sex offenders.
AB - The current study employed both latent variable- and person-centered approaches
to examine psychopathic traits in a large sample of sex offenders (N = 958). The
offenders, who had committed a range of sexual crimes, had been assessed with the
Psychopathy Checklist-Revised (PCL-R; Hare, 2003). Structural equation modeling
results indicated that the four-factor model of psychopathy (Hare, 2003; Neumann,
Hare, & Newman, 2007) provided good representation of the dimensional nature of
psychopathic traits across the sample of offenders, and that the PCL-R factors
significantly predicted sexual crimes. In particular, the Affective and
Antisocial psychopathy factors each predicted sexually violent crimes. Latent
profile analysis results revealed evidence for a 4-class solution, with the
subtypes showing distinct PCL-R facet profiles, consistent with previous
research. The four subtypes were validated using sexual crime profiles. The
prototypic psychopathy subtype (high on all 4 PCL-R facets) evidenced more
violent sexual offenses than did the other subtypes. Taken together, the results
demonstrate how variable- and person-centered approaches in combination can add
to our understanding of the psychopathy construct and its correlates. (PsycINFO
Database Record
PMID- 28406658
TI - The role of boldness in psychopathy: A study of academic and clinical
perceptions.
AB - The relevance of boldness to psychopathy has recently become a major flashpoint
of scientific controversy. Although some authors have contended that boldness is
a necessary (although insufficient) component of psychopathy, others have
asserted that it is largely or entirely irrelevant to psychopathy. We addressed
this issue by examining clinical perceptions of the relevance of the 3 triarchic
dimensions (boldness, disinhibition, and meanness) to psychopathy among a sample
of mental health professionals and graduate students (N = 228) using a vignette
based, person-centered methodology. A vignette comprising boldness descriptors
afforded statistically significant and moderate to large (Cohen's ds ranged from
.47 to .99) increases in perceived resemblance to overall psychopathy above and
beyond the other triarchic dimensions, both singly and jointly; these findings
extended largely to clinical perceptions of Factor 1 (i.e., interpersonal and
affective aspects of psychopathy) but not Factor 2 (i.e., impulsive and
antisocial aspects of psychopathy) resemblance. Contrary to the claims of some
recent authors, boldness alone was perceived as being as relevant to psychopathy
as was disinhibition, although both dimensions were perceived as less relevant to
psychopathy than was meanness. These findings offer strong support for the
contention that boldness is regarded as a key feature of classical psychopathy
and are broadly consistent with interpersonal models of psychopathy. (PsycINFO
Database Record
PMID- 28406659
TI - Does gratitude enhance prosociality?: A meta-analytic review.
AB - Theoretical models suggest that gratitude is linked to increased prosociality. To
date, however, there is a lack of a comprehensive quantitative synthesis of
results to support this claim. In this review we aimed to (a) examine the overall
strength of the association between gratitude and prosociality, and (b) identify
the theoretical and methodological variables that moderate this link. We
identified 252 effect sizes from 91 studies across 65 papers-(Total N = 18,342
participants). The present meta-analysis revealed a statistically significant,
and moderate positive correlation between gratitude and prosociality (r = .374).
This association was significantly larger among studies that assessed reciprocal
outcomes relative to nonreciprocal outcomes, and in particular among studies that
examined direct-compared with indirect-reciprocity. Studies that examined
gratitude as an affective state reported significantly larger effect size studies
assessing gratitude as a trait. Studies that examined benefit-triggered gratitude
(in response to other's kindness) had a stronger effect that generalized
gratitude that focuses on the appreciation of what is valued and cherished in
life. Finally, studies that manipulated gratitude in vivo (e.g., economic games)
had larger effect sizes compared with those based on recalled incidents when the
person felt grateful. We describe the theoretical and practical significance of
the results. (PsycINFO Database Record
PMID- 28406660
TI - Maternal pre- and postnatal mental health and infant development in war
conditions: The Gaza Infant Study.
AB - OBJECTIVE: Women and their infants need special protection in war context, as
traumatic events can risk maternal mental and obstetric health and compromise
infant development. This prospective study examined, first, how exposure to war
trauma is associated with maternal mental health in pregnancy and postpartum,
obstetric and newborn health, and infant development. Second, it tested the role
of maternal mental health and obstetric risks in mediating between war trauma and
infant development. METHOD: Palestinian women (N = 511) from the Gaza strip
participated during pregnancy (T1) and at 4 (T2) and 12 (T3) months postpartum.
They reported PTSD, depressive, anxiety, and dissociative symptoms, as well as
pregnancy complications, newborn health risks such as prematurity, and infant
sensorimotor and language development. RESULTS: First, exposure to war trauma was
associated with high levels of maternal mental health and complications at
pregnancy, and with increased postpartum mental health symptoms, but exposure was
not directly associated with newborn health risks or problems in infant
development. Second, maternal mental health both in pregnancy and postpartum, but
not pregnancy complications or newborn health, mediated the negative impact of
war trauma on infant sensorimotor and language development at 12 months.
CONCLUSION: Interventions to protect early child development in war conditions
should be tailored to support maternal mental health. (PsycINFO Database Record
PMID- 28406661
TI - Lifetime history of suicidal ideation and attempts among incarcerated women in
israel.
AB - BACKGROUND: Evidence indicates that rates of death by suicide are higher among
female inmates compared with male inmates and the general population. Despite the
high rate of lifetime suicidality, little is known about the predictors of
suicidality for these women. OBJECTIVE: The purpose was to examine
sociodemographic, criminological, and psychological variables associated with a
history of suicidal ideation and suicide attempts among incarcerated women.
METHOD: This cross-sectional study investigated a history of suicidal ideation
and suicide attempts in a sample of 46 Israeli incarcerated women. Participants
completed a confidential interview that included the Addiction Severity Index,
the Renard Diagnostic Interview, self-report measures of the Childhood Trauma
Questionnaire, and the presence of symptoms of depression. RESULTS: More than
half of the women reported a history of suicidal ideation or attempts. Those who
reported such a history were characterized by a high prevalence of childhood
victimization, early onset of substance abuse, high prevalence of mental health
problems, and high prevalence of mental health problems in the family. Child
abuse, depression, and family mental health problems are related to suicidal
ideation and attempts in incarcerated women. CONCLUSIONS: As the number of women
with mental health concerns entering prison grows, corrections staff are faced
with increasing challenges to provide services that mitigate the risk of death by
suicide. Inquiring about childhood abuse and symptoms of depression and mental
health problems, as well as providing treatment for the emotional impact of
trauma exposure, may reduce the risk of suicidality in this population. (PsycINFO
Database Record
PMID- 28406663
TI - Neuropsychological correlates of theory of mind deficits in patients with
multiple sclerosis.
AB - BACKGROUND: Theory of mind (ToM) is the ability to understand and interpret
another person's beliefs, intentions (cognitive ToM) and emotions (affective
ToM). OBJECTIVE: To explore affective and cognitive ToM and their
neuropsychological correlates in patients affected by multiple sclerosis (MS).
MATERIAL AND METHOD: Forty MS patients and 40 matched control individuals
underwent tasks assessing cognitive (the ToM Pictures Sequencing Task and the
Advanced Test of ToM) and affective ToM (the Reading the Mind in the Eyes Task
and the Emotion Attribution Task), in both verbal and nonverbal modality, a
comprehensive neuropsychological battery, and questionnaires for behavioral
disorders. RESULTS: MS patients performed significantly worse than controls on
tasks assessing cognitive and affective ToM, in verbal and nonverbal modality.
Moreover, MS patients achieved significantly lower scores on tests assessing
visuospatial learning and speed of spatial information processing, and
significantly higher scores on scales for alexithymia and depression with respect
to controls. After covarying for cognitive and behavioral variables different in
the 2 groups, the differences between patients and controls on ToM tasks remained
significant. ToM abilities were significantly related to executive functions, but
not to depressive, anxious and apathetic symptoms. Higher alexithymia scores were
associated with poor recognition of others' mental states. CONCLUSION: The
findings demonstrated that both affective and cognitive aspects of ToM are
impaired in nondemented and mildly to moderately disabled MS and suggest that
impaired social cognition can occur independently from behavioral disorders.
(PsycINFO Database Record
PMID- 28406664
TI - Spontaneous retrieval deficits in amnestic mild cognitive impairment: A case of
focal event-based prospective memory.
AB - OBJECTIVE: Research on early cognitive markers of Alzheimer's disease is
primarily focused on retrospective recall (of word lists, pairs of items,
stories) and executive functions. However, research shows that people with
amnestic mild cognitive impairment (aMCI), who are at a higher risk of developing
the disease than healthy controls, are particularly impaired in remembering to do
things in the future or prospective memory (PM). The aim of this study was to
establish which type of event-based PM is particularly disrupted in aMCI, focal
PM, based on spontaneous retrieval, or nonfocal PM that relies on strategic
monitoring processes. METHOD: Thirty-eight aMCI individuals and 46 age- and
education-matched healthy older adults identified the profession of each famous
face presented (ongoing task) and, additionally, responded to certain professions
(focal PM condition), or to certain physical features of a person presented
(nonfocal PM). Only 4 aMCI individuals could not remember PM instructions at the
end of the session, and were excluded from analyses. RESULTS: In comparison with
healthy controls, participants with aMCI were significantly impaired in the focal
PM task, but not on the nonfocal task. In both groups, monitoring indices were
significantly higher in the nonfocal than focal PM condition. CONCLUSIONS: The
results fully replicate and extend initial findings of Chi et al. (2014) and
McDaniel, Shelton, Breneiser, Moynan, and Balota (2011), showing substantial
spontaneous retrieval deficits in PM performance of aMCI individuals. Possible
brain mechanisms involved in this deficit are discussed and a novel hypothesis of
more generic spontaneous retrieval deficits in aMCI is proposed. (PsycINFO
Database Record
PMID- 28406662
TI - Explicit and implicit reinforcement learning across the psychosis spectrum.
AB - Motivational and hedonic impairments are core features of a variety of types of
psychopathology. An important aspect of motivational function is reinforcement
learning (RL), including implicit (i.e., outside of conscious awareness) and
explicit (i.e., including explicit representations about potential reward
associations) learning, as well as both positive reinforcement (learning about
actions that lead to reward) and punishment (learning to avoid actions that lead
to loss). Here we present data from paradigms designed to assess both positive
and negative components of both implicit and explicit RL, examine performance on
each of these tasks among individuals with schizophrenia, schizoaffective
disorder, and bipolar disorder with psychosis, and examine their relative
relationships to specific symptom domains transdiagnostically. None of the
diagnostic groups differed significantly from controls on the implicit RL tasks
in either bias toward a rewarded response or bias away from a punished response.
However, on the explicit RL task, both the individuals with schizophrenia and
schizoaffective disorder performed significantly worse than controls, but the
individuals with bipolar did not. Worse performance on the explicit RL task, but
not the implicit RL task, was related to worse motivation and pleasure symptoms
across all diagnostic categories. Performance on explicit RL, but not implicit
RL, was related to working memory, which accounted for some of the diagnostic
group differences. However, working memory did not account for the relationship
of explicit RL to motivation and pleasure symptoms. These findings suggest
transdiagnostic relationships across the spectrum of psychotic disorders between
motivation and pleasure impairments and explicit RL. (PsycINFO Database Record
PMID- 28406665
TI - Counting ability in Down syndrome: The comprehension of the one-to-one
correspondence principle and the role of receptive vocabulary.
AB - OBJECTIVE: The authors investigated whether children with Down's syndrome (DS)
who have not started to produce number words understand the one-to-one
correspondence principle (Experiment 1), and they looked at the relationship
between number word knowledge and receptive vocabulary (Experiment 2). METHOD:
Sixteen children with DS who did not recite the count list participated in
Experiment 1, along with 2 comparison groups: 1 of 16 children with DS who
recited up to 10, paired by chronological age, and another of 16 typically
developing children paired by their ability to recite the list. The understanding
of the principle was evaluated by a preferential looking task. Children saw 1 of
2 conditions. In the number condition, they heard number words and in the beep
condition they heard computerized beeps. In both conditions, children saw videos
depicting counting events that were principle-consistent or principle
inconsistent. Experiment 2 evaluated 25 children with DS using the Give-a-Number
task and the Receptive Vocabulary subtest of the Wechsler Preschool and Primary
Scale of Intelligence-III. RESULTS: In Experiment 1, children in the number
condition preferred principle-consistent videos, independent of their ability to
recite the count list. Experiment 2 showed a strong correlation between number
word knowledge and receptive vocabulary scores, independent of chronological age.
CONCLUSIONS: The results suggest that the difficulty of children with DS in
acquiring counting ability might not reflect a lack of understanding of the one
to-one correspondence principle, but might instead be related to vocabulary
development. (PsycINFO Database Record
PMID- 28406666
TI - Time course of motor gains induced by music-supported therapy after stroke: An
exploratory case study.
AB - OBJECTIVE: Previous studies have shown that Music-Supported Therapy (MST) can
improve the motor function and promote functional neuroplastic changes in motor
areas; however, the time course of motor gains across MST sessions and treatment
periods remain unknown. The aim of this study was to explore the progression of
the rehabilitation of motor deficits in a chronic stroke patient for a period of
7 months. METHOD: A reversal design (ABAB) was implemented in a chronic stroke
patient where no treatment was provided in the A periods and MST was applied in
the B periods. Each period comprised of 4 weeks and an extensive evaluation of
the motor function using clinical motor tests and 3D movement analysis was
performed weekly. During the MST periods, a keyboard task was recorded daily. A
follow-up evaluation was performed 3 months after the second MST treatment.
RESULTS: Improvements were observed during the first sessions in the keyboard
task but clinical gains were noticeable only at the end of the first treatment
and during the second treatment period. These gains were maintained in the follow
up evaluation. CONCLUSIONS: This is the first study examining the pattern of
motor recovery progression in MST, evidencing that gradual and continuous motor
improvements are possible with the repeated application of MST training. Fast
acquisition in specific motor abilities was observed at the beginning of the MST
training but generalization of these improvements to other motor tasks took place
at the end or when another treatment period was provided. (PsycINFO Database
Record
PMID- 28406667
TI - B. F. Skinner and technology's nation: Technocracy, social engineering, and the
good life in 20th-century America.
AB - Psychologist B. F. Skinner developed and promoted a technology of behavior as the
basis for widespread social reform over much of his career. In 1948, he published
his behaviorally engineered vision of the good life in his utopian novel Walden
Two (Skinner, 1948). Skinner's efforts were part of a much larger social
engineering tradition that received one of its fullest expressions in the
Technocracy Movement of the 1930s. Fifteen years before Skinner's Walden Two, at
the height of the Technocracy Movement's public visibility in the United States,
technocrat Harold Loeb (1933/1996) published his utopia, Life in a Technocracy:
What It Might Be Like. In this article, I place the socially engineered visions
of the good life promoted by the Technocracy Movement and by Skinner on an
intellectual and ideological continuum to amplify and explore American attitudes
toward psychology, technology, and social engineering during the middle decades
of the 20th century. I argue that responses to both reveal the possibilities and
limits of the social engineering enterprise, and suggest that historians of
technology might consider how the history of psychology and other psy-disciplines
can deepen conceptualizations of the relationships among the psychological, the
social, and the technological in this period. (PsycINFO Database Record
PMID- 28406668
TI - Beyond indifference and aversion: The critical reception and belated acceptance
of behavior therapy in France.
AB - In 1960s France, behavior therapy attracted the attention of a group of isolated
pioneers largely composed of psychiatrists and some experimental psychologists.
At the beginning of the 1970s, after a discreet introduction, the development of
this movement provoked an adverse reaction related to the French intellectual
context, which was characterized by a taste for psychoanalysis. At the height of
the Cold War, this new form of therapy was, moreover, seen as a typical product
of American culture, and viewed as a technique for mind control that would be
incompatible with French humanist values. In this respect, the French rejection
of behavioral therapies can also be placed in a broader context, one of anti
Americanism and assertion of the French "cultural exception." Thus, until the
late 1980s, the development of the French behavior therapy movement was weak
compared with what happened in the United Kingdom or the United States.
Conversely, psychoanalysis reigned unchallenged in the French market for
psychotherapy. In the early 1990s, the arrival of cognitive-behavioral therapy
made a crucial difference. Hybridized with cognitive techniques, cognitive
behavioral therapy was seen as a "synthetic product" better suited to the French
culture in psychotherapy than the initial model of "pure" behavior therapy.
(PsycINFO Database Record
PMID- 28406669
TI - Methodology of performance scoring in the d2 sustained-attention test: Cumulative
reliability functions and practical guidelines.
AB - We provide a psychometric analysis of commonly used performance indices of the d2
sustained-attention test, and give methodical guidelines and recommendations,
based on this research. We examined experimental effects of repeated testing on
performance speed and accuracy (omission and commission errors), and further
evaluated aspects of test reliability by means of cumulative reliability function
(CRF) analysis. These aspects were also examined for a number of alternative (yet
commonly used) scoring techniques and valuation methods. Results indicate that
performance is sensitive to change, both differentially within (time-on-task) and
between (test-retest) sessions. These effects did not severely affect test
reliability, since perfect score reliability was observed for measures of speed
(and was even preserved with half the test length) while variability and error
scores were more problematic with respect to reliability. Notably, limitations
particularly hold for commission but less so for omission errors. Our
recommendations to researchers and practitioners are that (a) only the speed
score (and error-corrected speed score) is eligible for highly reliable
assessment, that (b) error scores might be used as a secondary measure (e.g., to
check for aberrant behavior), that (c) variability scores might not be used at
all. Given the exceptional reliability of performance speed, and (d) test length
may be reduced up to 50%, if necessary for time-economic reasons, to serve
purposes of population screening and field assessment. (PsycINFO Database Record
PMID- 28406670
TI - Latent difference score modeling: A flexible approach for studying informant
discrepancies.
AB - The current study proposes a flexible approach to studying informant
discrepancies: Latent Difference Scores modeling (LDS). The LDS approach is
demonstrated using an empirical example in which associations between mother
adolescent and father-adolescent discrepant parenting perceptions, and concurrent
and later adolescent externalizing behaviors, were investigated. Early
adolescents (N = 477, aged 12-15 years), mothers (N = 470), and fathers (N = 440)
filled out questionnaires about mothers' and fathers' parenting. Results using
the LDS approach are compared to results obtained by the 2 existing approaches
for informant discrepancies: Observed Difference Scores modeling (ODS) and
Polynomial Regression Analyses (PRA). Results from the LDS approach show that
adolescents perceive their mothers' and fathers' parenting less favorably than
mothers and fathers themselves, and that stronger mother-adolescent discrepancies
are consistently related to stronger father-adolescent discrepancies. Parent
adolescent discrepancies were concurrently associated with more aggressive and
rule-breaking behaviors, but not longitudinally. Results generalized across the 2
discrepancy approaches, but only very few significant associations were found in
the PRA. Advantages and limitations of all 3 approaches to studying informant
discrepancies are discussed. (PsycINFO Database Record
PMID- 28406671
TI - A comparison of self-report measures of psychopathy among nonforensic samples
using item response theory analyses.
AB - This study investigated how well components of the psychopathy trait are measured
among college students with the Levenson Self-Report Psychopathy Scale (LSRP),
the Personality Assessment Inventory-Antisocial Features Scale (PAI ANT), the
Psychopathic Personality Inventory-Short Form (PPI-SF), and the Self-Report
Psychopathy Scale-II (SRP-II). Using Samejima (1969)'s graded response model
(GRM), the subscales were found to vary in their ability to measure the
corresponding latent traits. The LSRP primary psychopathy factor is more precise
in measuring the latent trait than the secondary psychopathy factor. The PAI ANT
items show coherent psychometric properties, whereas the PPI-SF factors differ in
their precision to measure the corresponding traits. The SRP-II factors are
effective in discriminating among individuals with varying levels of the latent
traits. Results suggest that multiple self-report measures should be used to tap
the multidimensional psychopathy construct. However, there are concerns with
respect to using negatively worded items to assess certain aspects of
psychopathy. (PsycINFO Database Record
PMID- 28406673
TI - Bayesian unknown change-point models to investigate immediacy in single case
designs.
AB - Although immediacy is one of the necessary criteria to show strong evidence of a
causal relation in single case designs (SCDs), no inferential statistical tool is
currently used to demonstrate it. We propose a Bayesian unknown change-point
model to investigate and quantify immediacy in SCD analysis. Unlike visual
analysis that considers only 3-5 observations in consecutive phases to
investigate immediacy, this model considers all data points. Immediacy is
indicated when the posterior distribution of the unknown change-point is narrow
around the true value of the change-point. This model can accommodate delayed
effects. Monte Carlo simulation for a 2-phase design shows that the posterior
standard deviations of the change-points decrease with increase in standardized
mean difference between phases and decrease in test length. This method is
illustrated with real data. (PsycINFO Database Record
PMID- 28406672
TI - Measuring working memory in the Spanish population: Validation of a multiple
shortened complex span task.
AB - Working memory plays a key role in cognition as it is a major predictor of a wide
range of higher order abilities and behaviors typical to daily life. Shorter
versions of the complex span tasks (CSTs) have been recently developed, allowing
for the reduction of test administration time without affecting validity and
reliability in the measurement of working memory capacity (WMC). However, these
short versions have not been validated for the Spanish-speaking population. The
present work aimed to validate an English version of the shortened CSTs into
Spanish in a sample of 325 university students (40% female; mean age = 21.04; SD
= 2.80). Cronbach's coefficient alpha was computed for each complex span task as
an index of internal consistency. Validity evidence was evaluated by comparing
participants' scores on the three shortened complex span tasks (operation span,
symmetry span, and rotation span) with two measures of reasoning ability (Raven's
Advanced Progressive Matrices and Number Series) and using confirmatory factor
analysis. Results indicated that the short version of the Spanish complex span
has satisfying qualities for assessing WMC in a sample of university students,
which is an initial step toward providing a valid and standardized method for
assessing WMC in the Peninsular Spanish-speaking population. (PsycINFO Database
Record
PMID- 28406675
TI - How does it "feel"? A signal detection approach to feeling generation.
AB - Feeling, or the subjective emotional experience, is a fundamental element of the
emotional reaction, yet past attempts to understand the mechanisms of feeling
generation remain limited. The current study presents a signal detection theory
(SDT) conceptualization of feeling generation. Accordingly, feeling, like other
sensations, reflects an outcome of an inner decision regarding the emotional
evidence, and, therefore, can be evaluated via 2 processes: evidence
differentiation (d')-the ability to emotionally differentiate between external
stimuli, given the essentially noisy evidence-and criterion (c)-the report
threshold, or amount of evidence needed to have an intense reportable feeling.
According to the model, feelings can be disproportionally intense (false alarms;
e.g., emotional overreaction) or disproportionally weak (misses; e.g., failing to
detect danger), with the criterion controlling the relative proportion of these
"errors." Results from a novel task indicate that our conceptualization provides
a suitable model for valence (pleasant-unpleasant) feeling generation, as
reflected in superior model fit relative to plausible alternative models,
nonsignificant lack of fit, and by successful experimental tests of a novel
prediction regarding contextual influences and related uncertainty. Additional
evidence for the external validity of the model shows that SDT parameters,
especially the criterion, were meaningfully correlated with relevant emotion
regulation and affective style constructs. Implications for the understanding of
feeling generation, in general, and in psychopathology, in particular, are
discussed. (PsycINFO Database Record
PMID- 28406674
TI - Randomization to randomization probability: Estimating treatment effects under
actual conditions of use.
AB - Blinded randomized controlled trials (RCT) require participants to be uncertain
if they are receiving a treatment or placebo. Although uncertainty is ideal for
isolating the treatment effect from all other potential effects, it is poorly
suited for estimating the treatment effect under actual conditions of intended
use-when individuals are certain that they are receiving a treatment. We propose
an experimental design, randomization to randomization probabilities (R2R), which
significantly improves estimates of treatment effects under actual conditions of
use by manipulating participant expectations about receiving treatment. In the
R2R design, participants are first randomized to a value, pi, denoting their
probability of receiving treatment (vs. placebo). Subjects are then told their
value of pi and randomized to either treatment or placebo with probabilities pi
and 1-pi, respectively. Analysis of the treatment effect includes statistical
controls for pi (necessary for causal inference) and typically a pi-by-treatment
interaction. Random assignment of subjects to pi and disclosure of its value to
subjects manipulates subject expectations about receiving the treatment without
deception. This method offers a better treatment effect estimate under actual
conditions of use than does a conventional RCT. Design properties, guidelines for
power analyses, and limitations of the approach are discussed. We illustrate the
design by implementing an RCT of caffeine effects on mood and vigilance and show
that some of the actual effects of caffeine differ by the expectation that one is
receiving the active drug. (PsycINFO Database Record
PMID- 28406676
TI - Trait acceptance predicts fewer daily negative emotions through less stressor
related rumination.
AB - People who are more accepting of their thoughts and feelings experience fewer
negative emotions. Although several studies document the connection between
acceptance and negative emotions, little, if any research, sheds light on how
being receptive to one's internal experience results in less negativity in
everyday life. In a daily diary study (N = 183), we found that people who were
more accepting of their thoughts and feelings experienced fewer daily negative
emotions, and this association was partly explained by less daily stressor
related rumination. The strength of this mediational pathway differed depending
upon the average perceived severity of daily stressors. When daily stressors were
perceived to be more demanding, trait acceptance predicted a stronger inverse
association with rumination, and rumination predicted a stronger positive
association with negative emotions. These results shed light on one way
acceptance of internal experience predicts less negativity, as well as the
moderating role of perceived daily stress. (PsycINFO Database Record
PMID- 28406677
TI - No impact of affective person knowledge on visual awareness: Evidence from
binocular rivalry and continuous flash suppression.
AB - Stimuli with intrinsic emotional value, like emotional faces, and stimuli
associated with reward and punishment are often prioritized in visual awareness
relative to neutral stimuli. Recently, Anderson, Siegel, Bliss-Moreau, and
Barrett (2011) demonstrated that simply associating a face with affective
knowledge can also influence visual awareness. Using a binocular rivalry task
(BR), where a face was shown to one eye and a house to the other, they found that
faces paired with negative versus neutral and positive behaviors dominated visual
awareness. We were interested in whether faces associated with negative
information would also be capable of reaching awareness more quickly in the first
place. To test this, we set out to replicate Anderson and colleagues' finding and
to examine whether it would extend to breaking continuous flash suppression (b
CFS), a technique where a dynamic mask shown to one eye initially suppresses the
stimulus shown to the other eye. Participants completed a learning task followed
by BR and b-CFS tasks, in counterbalanced order. Across both tasks, faces
associated with negative behaviors were treated no differently from faces
associated with neutral or positive behaviors. However, faces associated with any
type of behavior were prioritized in awareness over novel faces. These findings
indicate that while familiarity influences conscious perception, the influence of
affective person knowledge on visual awareness is more circumscribed than
previously thought. (PsycINFO Database Record
PMID- 28406678
TI - Genetic and environmental influences on emotion regulation: A twin study of
cognitive reappraisal and expressive suppression.
AB - Previous studies have established that personality traits related to emotionality
are moderately heritable. However, the relative heritability of the strategies
people use to regulate emotions is unknown. The present study compared the
magnitude of additive genetic, shared environmental, and nonshared environmental
influences on 2 commonly used emotion regulation strategies: cognitive
reappraisal and expressive suppression. In 743 twin pairs (1,486 twins), we
replicated previous estimates of heritability of neuroticism (a2 = .41).
Furthermore, cognitive reappraisal was significantly less heritable and more
influenced by nonshared environment (a2 = .20; e2 = .80) than either neuroticism
or suppression (a2 = .35; e2 = .65), another emotion regulation strategy.
Finally, Cholesky decomposition modeling suggested that while there were common
genetic and environmental influences on neuroticism, reappraisal and suppression,
there were also significant nonshared environmental influences common between
reappraisal and adaptive emotional functioning after controlling for neuroticism
and suppression. These findings highlight that different aspects of emotional
processing, even the use of different emotion regulation strategies, are
differentially heritable. The importance of the nonshared environmental
influences specific to reappraisal and adaptive emotional functioning speaks to
the potential impact of social context, social partners, and psychosocial
interventions on reappraisal habits. (PsycINFO Database Record
PMID- 28406679
TI - Gently does it: Humans outperform a software classifier in recognizing subtle,
nonstereotypical facial expressions.
AB - According to dominant theories of affect, humans innately and universally express
a set of emotions using specific configurations of prototypical facial activity.
Accordingly, thousands of studies have tested emotion recognition using sets of
highly intense and stereotypical facial expressions, yet their incidence in real
life is virtually unknown. In fact, a commonplace experience is that emotions are
expressed in subtle and nonprototypical forms. Such facial expressions are at the
focus of the current study. In Experiment 1, we present the development and
validation of a novel stimulus set consisting of dynamic and subtle emotional
facial displays conveyed without constraining expressers to using prototypical
configurations. Although these subtle expressions were more challenging to
recognize than prototypical dynamic expressions, they were still well recognized
by human raters, and perhaps most importantly, they were rated as more ecological
and naturalistic than the prototypical expressions. In Experiment 2, we examined
the characteristics of subtle versus prototypical expressions by subjecting them
to a software classifier, which used prototypical basic emotion criteria.
Although the software was highly successful at classifying prototypical
expressions, it performed very poorly at classifying the subtle expressions.
Further validation was obtained from human expert face coders: Subtle stimuli did
not contain many of the key facial movements present in prototypical expressions.
Together, these findings suggest that emotions may be successfully conveyed to
human viewers using subtle nonprototypical expressions. Although classic
prototypical facial expressions are well recognized, they appear less
naturalistic and may not capture the richness of everyday emotional
communication. (PsycINFO Database Record
PMID- 28406680
TI - Happier than thou? A self-enhancement bias in emotion attribution.
AB - People tend to judge themselves as exhibiting above average levels of desirable
traits-including competence, kindness, and life satisfaction-but does this self
enhancement extend to emotional responses? Here, we explore this question by
having people attribute emotions to themselves and others following simple
gambles. We demonstrate that people display an emotional self-enhancement bias
that varies with the context of the emotion-eliciting situation. People judge
themselves as experiencing more positive emotional reactions on average, and they
also believed that others' emotions are more sensitive to gamble outcomes, such
that people judge others to experience stronger negative affect in response to
negative outcomes (Study 1). This self-enhancement bias further tracks social
distance, such that people attribute less positive and more negative emotion to
more dissimilar, as compared with more similar others (Study 2). People also
predict less favorable emotional states for themselves and others experiencing
events in the future, as compared with the present (Study 3), suggesting that
this attribution bias extends across multiple dimensions of psychological
distance. Broadly, these data suggest that people exhibit self-enhancement in
emotion attribution, but do so in subtle ways that depend on situational and
social factors. (PsycINFO Database Record
PMID- 28406681
TI - Affective enhancement of working memory is maintained in depression.
AB - We currently know little about how performance on assessments of working memory
capacity (WMC) that are designed to mirror the concurrent task demands of daily
life are impacted by the presence of affective information, nor how those effects
may be modulated by depression-a syndrome where sufferers report global
difficulties with executive processing. Across 3 experiments, we investigated WMC
for sets of neutral words in the context of processing either neutral or
affective (depressogenic) sentences, which had to be judged on semantic accuracy
(Experiments 1 and 2) or self-reference (Experiment 3). Overall, WMC was
significantly better in the context of depressogenic compared with neutral
sentences. However, there was no support for this effect being modulated by
symptoms of depression (Experiment 1) or the presence of recurrent major
depressive disorder (MDD; Experiments 2 and 3). Implications of these findings
for cognitive theories of the role of WM in depression are discussed in the
context of a growing body of research showing no support for a differential
impact of depressogenic compared with neutral information on WM accuracy.
(PsycINFO Database Record
PMID- 28406682
TI - Overcoming indecision by changing the decision boundary.
AB - The dominant theoretical framework for decision making asserts that people make
decisions by integrating noisy evidence to a threshold. It has recently been
shown that in many ecologically realistic situations, decreasing the decision
boundary maximizes the reward available from decisions. However, empirical
support for decreasing boundaries in humans is scant. To investigate this
problem, we used an ideal observer model to identify the conditions under which
participants should change their decision boundaries with time to maximize reward
rate. We conducted 6 expanded-judgment experiments that precisely matched the
assumptions of this theoretical model. In this paradigm, participants could
sample noisy, binary evidence presented sequentially. Blocks of trials were fixed
in duration, and each trial was an independent reward opportunity. Participants
therefore had to trade off speed (getting as many rewards as possible) against
accuracy (sampling more evidence). Having access to the actual evidence samples
experienced by participants enabled us to infer the slope of the decision
boundary. We found that participants indeed modulated the slope of the decision
boundary in the direction predicted by the ideal observer model, although we also
observed systematic deviations from optimality. Participants using suboptimal
boundaries do so in a robust manner, so that any error in their boundary setting
is relatively inexpensive. The use of a normative model provides insight into
what variable(s) human decision makers are trying to optimize. Furthermore, this
normative model allowed us to choose diagnostic experiments and in doing so we
present clear evidence for time-varying boundaries. (PsycINFO Database Record
PMID- 28406684
TI - Redundant encoding strengthens segmentation and grouping in visual displays of
data.
AB - The availability and importance of data are accelerating, and our visual system
is a critical tool for understanding it. The research field of data visualization
seeks design guidelines-often inspired by perceptual psychology-for more
efficient visual data analysis. We evaluated a common guideline: When presenting
multiple sets of values to a viewer, those sets should be distinguished not just
by a single feature, such as color, but redundantly by multiple features, such as
color and shape. Despite the broad use of this practice across maps and graphs,
it may carry costs, and there is no direct evidence for a benefit. We show that
this practice can indeed yield a large benefit for rapidly segmenting objects
within a dense display (Experiments 1 and 2), and strengthening visual grouping
of display elements (Experiment 3). We predict situations where this benefit
might be present, and discuss implications for models of attentional control.
(PsycINFO Database Record
PMID- 28406683
TI - Evaluating the sources and functions of gradiency in phoneme categorization: An
individual differences approach.
AB - During spoken language comprehension listeners transform continuous acoustic cues
into categories (e.g., /b/ and /p/). While long-standing research suggests that
phonetic categories are activated in a gradient way, there are also clear
individual differences in that more gradient categorization has been linked to
various communication impairments such as dyslexia and specific language
impairments (Joanisse, Manis, Keating, & Seidenberg, 2000; Lopez-Zamora, Luque,
Alvarez, & Cobos, 2012; Serniclaes, Van Heghe, Mousty, Carre, & Sprenger
Charolles, 2004; Werker & Tees, 1987). Crucially, most studies have used 2
alternative forced choice (2AFC) tasks to measure the sharpness of between
category boundaries. Here we propose an alternative paradigm that allows us to
measure categorization gradiency in a more direct way. Furthermore, we follow an
individual differences approach to (a) link this measure of gradiency to multiple
cue integration, (b) explore its relationship to a set of other cognitive
processes, and (c) evaluate its role in individuals' ability to perceive speech
in noise. Our results provide validation for this new method of assessing phoneme
categorization gradiency and offer preliminary insights into how different
aspects of speech perception may be linked to each other and to more general
cognitive processes. (PsycINFO Database Record
PMID- 28406685
TI - Individual differences in working memory capacity predict learned control over
attentional capture.
AB - Although individual differences in working memory capacity (WMC) typically
predict susceptibility to attentional capture in various paradigms (e.g., Stroop,
antisaccade, flankers), it sometimes fails to correlate with the magnitude of
attentional capture effects in visual search (e.g., Stokes, 2016), which is 1 of
the most frequently studied tasks to study capture (Theeuwes, 2010). But some
studies have shown that search modes can mitigate the effects of attentional
capture (Leber & Egeth, 2006). Therefore, the present study examined whether or
not the relationship between WMC and attentional capture changes as a function of
the search modes available. In Experiment 1, WMC was unrelated to attentional
capture, but only 1 search mode (singleton-detection) could be employed. In
Experiment 2, greater WMC predicted smaller attentional capture effects, but only
when multiple search modes (feature-search and singleton-detection) could be
employed. Importantly this relationship was entirely independent of variation in
attention control, which suggests that this effect is driven by WMC-related long
term memory differences (Cosman & Vecera, 2013a, 2013b). The present set of
findings help to further our understanding of the nuanced ways in which memory
and attention interact. (PsycINFO Database Record
PMID- 28406686
TI - Cueing cognitive flexibility: Item-specific learning of switch readiness.
AB - The rich behavioral repertoire of the human species derives from our ability to
flexibly reconfigure processing strategies (task sets) in response to changing
requirements. This updating of task sets is effortful, as reflected by longer
response times when switching a task than repeating it (switch costs). However,
some recent data suggest that switch costs can be reduced by cueing switch
readiness bottom-up, by associating particular stimuli with frequent switch
requirements. This type of "stimulus-control (S-C) learning" would be highly
adaptive, as it combines the speed of automatic (bottom-up) processing with the
flexibility and generalizability of controlled (top-down) processing. However, it
is unclear whether S-C learning of switch readiness is truly possible, and what
the underlying mechanisms are. Here we address these questions by pairing
specific stimuli with a need to update task-sets either frequently or rarely. In
all 3 experiments, we observe robust item-specific switch probability (ISSP)
effects as revealed by smaller switch costs for frequent switch items than for
rare switch items. By including a neutral condition, we also show that the ISSP
effect is primarily driven by S-C learning reducing switch costs in frequent
switch items. Furthermore, by employing 3 tasks in Experiment 3, we establish
that the ISSP effect reflects an enhancement of general switch readiness, rather
than of the readiness to switch to a specific alternate task. These results
firmly establish that switch readiness is malleable by item-specific S-C learning
processes, documenting that a generalizable state of cognitive flexibility can be
primed by a bottom-up stimulus. (PsycINFO Database Record
PMID- 28406687
TI - Investigating the relationship between media multitasking and processes involved
in task-switching.
AB - Although multitasking with media has increased dramatically in recent years
(Rideout, Foehr, & Roberts, 2010), the association between media multitasking and
cognitive performance is poorly understood. In addition, the literature on the
relationship between media multitasking and task-switching, one measure of
cognitive control, has produced mixed results (Alzahabi & Becker, 2013; Minear et
al., 2013; Ophir, Nass, & Wagner, 2009). Here we use an individual differences
approach to investigate the relationship between media multitasking and task
switching performance by first examining the structure of task-switching and
identifying the latent factors that contribute to switch costs. Participants
performed a series of 3 different task-switching paradigms, each designed to
isolate the effects of a specific putative mechanism (e.g., advanced preparation)
related to task-switching performance, as well as a series of surveys to measure
media multitasking and intelligence. The results suggest that task-switching
performance is related to 2 somewhat independent factors, namely an advanced
preparation factor and passive decay factor. In addition, multitasking with media
was related to a faster ability to prepare for tasks, resulting in faster task
switching performance without a cost to accuracy. Media multitasking and
intelligence were both unrelated to passive decay factors. These findings are
consistent with a 2-component model of task-switching (Sohn & Anderson, 2001), as
well as an automatic/executive framework of cognitive control (Schneider &
Shiffrin, 1977). (PsycINFO Database Record
PMID- 28406688
TI - Reading sentences of uniform word length: Evidence for the adaptation of the
preferred saccade length during reading.
AB - In the current study, the effect of removing word length variability within
sentences on spatial aspects of eye movements during reading was investigated.
Participants read sentences that were uniform in terms of word length, with each
sentence consisting entirely of three-, four-, or five-letter words, or a
combination of these word lengths. Several interesting findings emerged.
Adaptation of the preferred saccade length occurred for sentences with different
uniform word length; participants would be more accurate at making short saccades
while reading uniform sentences of three-letter words, while they would be more
accurate at making long saccades while reading uniform sentences of five-letter
words. Furthermore, word skipping was affected such that three- and four-letter
words were more likely, and five-letter words less likely, to be directly fixated
in uniform compared to non-uniform sentences. It is argued that saccadic
targeting during reading is highly adaptable and flexible toward the
characteristics of the text currently being read, as opposed to the idea
implemented in most current models of eye movement control during reading that
readers develop a preference for making saccades of a certain length across a
lifetime of experience with a given language. (PsycINFO Database Record
PMID- 28406689
TI - Caloric primary rewards systematically alter time perception.
AB - Human time perception can be influenced by contextual factors, such as the
presence of reward. Yet, the exact nature of the relationship between time
perception and reward has not been conclusively characterized. We implemented a
novel experimental paradigm to measure estimations of time across a range of
suprasecond intervals, during the anticipation and after the consumption of fruit
juice, a physiologically relevant primary reward. We show that average time
estimations were systematically affected by the consumption of reward, but not by
the anticipation of reward. Compared with baseline estimations of time, reward
consumption was associated with subsequent overproductions of time, and this
effect increased for larger magnitudes of reward. Additional experiments
demonstrated that the effect of consumption did not extend to a secondary reward
(money), a tasteless, noncaloric primary reward (water), or a sweet, noncaloric
reward (aspartame). However, a tasteless caloric reward (maltodexrin) did induce
overproductions of time, although this effect did not scale with reward
magnitude. These results suggest that the consumption of caloric primary rewards
can alter time perception, which may be a psychophysiological mechanism by which
organisms regulate homeostatic balance. (PsycINFO Database Record
PMID- 28406690
TI - The inversion, part-whole, and composite effects reflect distinct perceptual
mechanisms with varied relationships to face recognition.
AB - Face recognition is thought to rely on specific mechanisms underlying a
perceptual bias toward processing faces as undecomposable wholes. This face
specific "holistic processing" is commonly quantified using 3 measures: the
inversion, part-whole, and composite effects. Consequently, many researchers
assume that these 3 effects measure the same cognitive mechanism(s) and these
mechanisms contribute to the wide range of individual differences seen in face
recognition ability. We test these assumptions in a large sample (N = 282), with
individual face recognition abilities measured by the well-validated Cambridge
Face Perception Test. Our results provide little support for either assumption.
The small to nonexistent correlations among inversion, part-whole, and composite
effects (correlations between -.03 and .28) fail to support the first assumption.
As for the second assumption, only the inversion effect moderately predicts face
recognition (r = .42); face recognition was weakly correlated with the part-whole
effect (r = .25) and not correlated with the composite effect (r = .04). We rule
out multiple artifactual explanations for our results by using valid tasks that
produce standard effects at the group level, demonstrating that our tasks exhibit
psychometric properties suitable for individual differences studies, and
demonstrating that other predicted correlations (e.g., between face perception
measures) are robust. Our results show that inversion, part-whole, and composite
effects reflect distinct perceptual mechanisms, and we argue against the use of
the single, generic term holistic processing when referring to these effects. Our
results also question the contribution of these mechanisms to individual
differences in face recognition. (PsycINFO Database Record
PMID- 28406691
TI - Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer's
disease.
AB - Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and
elderly worldwide. Animal models for AD are widely used to study the disease
mechanisms as well as to test potential therapeutic agents for disease
modification. Among the non-genetically manipulated neuroinflammation models for
AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review
paper aims to discuss the possible factors that influence rats' response
following LPS injection. Factors such as dose of LPS, route of administration,
nature and duration of exposure as well as age and gender of animal used should
be taken into account when designing a study using LPS-induced memory impairment
as model for AD.
PMID- 28406692
TI - Effect of pre- and post-weaning high-fat dietary manipulation on intestinal
microflora and alkaline phosphatase activity in male rats.
AB - We investigated the impact of a high-fat (HF) diet during pre- and post-weaning
periods on the intestinal microbiota and alkaline phosphatase (AP) activity in
male rats. Nutrition from birth was influenced by feeding rat dams with either a
standard or HF diet. After weaning male pups nursed by control dams continued on
a standard diet (CC) or HF diet (C->HF), while offspring nursed by HF dams
continued on HF diet (HF) or standard diet (HF->C). The numbers of
Bacteroides/Prevotella (BAC) and Lactobacillus/Enterococcus (LAB) in the gut were
determined by FISH technique. HF pups displayed enhanced adiposity and increased
AP activity (19 %), as well as higher LAB (P<0.001) and lower numbers of BAC
(P<0.001) in the jejunum and colon than controls. In HF->C rats, post-weaning
lower fat intake resulted in decreased fat deposition accompanied by reduced AP
activity (20 %) compared to HF rats. Composition of the intestinal microbiota in
these rats was not influenced. In contrast, in comparison with controls, C->HF
rats displayed higher LAB (P<0.001) and lower BAC (P<0.001) together with
increased adiposity and AP activity (14 %). These results indicate that
consumption of diet with different fat content could modulate gut
microbial/functional conditions depending on the period when the nutritional
manipulation occurs.
PMID- 28406693
TI - Polychlorinated biphenyl 153 in lipid medium modulates differentiation of human
adipocytes.
AB - Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in
the development of diabetes mellitus in the obese. The purpose of this study was
to determine mechanisms by which PCB 153 (2,2',4,4',5,5'-hexachloro-biphenyl)
could influence diet-induced obesity and insulin resistance during adipogenesis.
Lineage of h-ADMSCs was differentiated either as control (differentiation medium
only), or with lipid vehicle modeling high fat nutrition (NuTRIflex) or lipid
free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co
exposure (in three concentrations 0.1, 1, and 10 microM). Gene expression
analyses were performed using RT-qPCR at days 4, 10, 21, 24, 28; protein levels
Akt and phosphorylated Akt (Phospho-Akt) by Western blot at days 4, and 21. PCB
153 treatment of h-ADMSCs only in lipid vehicle was associated with down
regulation of key master genes of adipogenesis: PPARgamma, SREBP-1, PPARGC1B, and
PLIN2 during the whole process of differentiation; and with increased Akt and
decreased Phospho-Akt protein level at day 21. We have shown that PCB 153, in
concentration 0.1 microM, has a potential in lipid rich environment to modulate
differentiation of adipocytes. Because European and U.S. adults have been exposed
to PCB 153, this particular nutrient-toxicant interaction potentially impacts
human obesity and insulin sensitivity.
PMID- 28406694
TI - Does inhibition of aldose reductase contribute to the anti-inflammatory action of
setipiprant?
AB - The aim of this study was to investigate aldose reductase inhibitory action of
setipiprant as a potential additional mechanism contributing to its anti
inflammatory action. Aldose reductase activity was determined by
spectrophotometric measuring of NADPH consumption. Setipiprant was found to
inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4
hydroxynonenal glutathione and prostaglandin H2 substrates, all relevant to the
process of inflammation. Molecular modeling simulations into the aldose reductase
inhibitor binding site revealed an interaction pattern of setipiprant.
Considering multifactorial etiology of inflammatory pathologies, it is suggested
that, in addition to the antagonizing prostaglandin D2 receptor, inhibition of
aldose reductase may contribute to the reported anti-inflammatory action of
setipiprant.
PMID- 28406695
TI - Visfatin is actively secreted in vitro from U-937 macrophages, but only passively
released from 3T3-L1 adipocytes and HepG2 hepatocytes.
AB - Visfatin is a multi-functional molecule that can act intracellularly and
extracellularly as an adipokine, cytokine and enzyme. One of the main questions
concerning visfatin is the mechanism of its secretion; whether, how and from
which cells visfatin is released. The objective of this in vitro study was to
observe the active secretion of visfatin from 3T3-L1 preadipocytes and
adipocytes, HepG2 hepatocytes, U-937, THP-1 and HL-60 monocytes and macrophages.
The amount of visfatin in media and cell lysate was always related to the
intracellular enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), to
exclude the passive release of visfatin. Visfatin was not found in media of 3T3
L1 preadipocytes. In media of 3T3-L1 adipocytes and HepG2 hepatocytes, the ratio
of visfatin to the amount of GAPDH was identical to cell lysates. Hence, it is
likely that these cells do not actively secrete visfatin in a significant manner.
However, we found that significant producers of visfatin are differentiated
macrophages and that the amount of secreted visfatin depends on used cell line
and it is affected by the mode of differentiation. Results show that 3T3-L1
adipocytes and HepG2 hepatocytes released visfatin only passively during the cell
death. U-937 macrophages secrete visfatin in the greatest level from all of the
tested cell lines.
PMID- 28406696
TI - Proteomic approach for identification of IgA nephropathy-related biomarkers in
urine.
AB - Proteinuria is often used as a surrogate marker in monitoring and predicting
outcome in patients with chronic kidney diseases, but it is non-specific. IgAN
belongs to the most common primary glomerulonephritis worldwide with serious
prognosis. The main aim of this work was to assess differences in urine proteins
in patients with IgA nephropathy and to identify abnormal proteins as potential
biomarkers of IgA nephropathy or the renal disease. In our pilot project, we
selected 20 patients and compared them with 20 healthy volunteers. Protein
quantification was performed using iTRAQ (isobaric tag for relative and absolute
quantitation) labeling method. The peptides were separated by the isoelectric
focusing method (IEF) and nano-LC with C18 column and identified by mass
spectrometry using MALDI-TOF/TOF MS. Proteins' lists obtained from IEF-LC-MS
MS/MS analysis were combined and contained 201 proteins. It was found out that
113 proteins were common in both experiments. 30 urinary proteins were
significantly up- or down-regulated in patients with IgA nephropathy. We
characterized potential biomarkers such as alpha-1-antitrypsin, apolipoprotein A
I, CD44 antigen or kininogen. Potential biomarkers of IgAN should be validated in
further studies.
PMID- 28406697
TI - How do we love? Romantic love style in men is related to lower testosterone
levels.
AB - Testosterone has been widely investigated in associations with many aspects of
social interactions, emotions and behavior. No research has been conducted on its
contribution to the variability of love styles in human. The aim of this paper
was to uncover the possible relationship between not only the actual plasma
testosterone levels, but also the prenatal testosterone level (expressed as 2D:4D
ratio) and the sensitivity of androgen receptor and love typology in young
healthy men. There are six love styles which are primary including Eros
(passionate romantic love), Ludus (playful) and Storge (friendly) and secondary
love consisting of Mania (obsessive), Pragma (practical realistic) and Agape
(altruistic). Our results pointed out that low testosterone concentrations are
associated with higher score for Eros, Ludus, Pragma, Mania love style. No
significant association was proved for other tested parameters of androgenicity
(2D:4D, sensitivity of androgen receptor) and love style after correction was
applied. Different attitudes and behavior in relationships do have a biological
foundation related to endogenous testosterone levels in plasma. Future studies
should address questions about the family and social background of participants
to differentiate here between moral rules or/and social-conventional rules.
PMID- 28406699
TI - Early morphologic alterations in renal artery wall and renal nerves in response
to catheter-based renal denervation procedure in sheep: difference between single
point and multiple-point ablation catheters.
AB - Renal sympathetic hyperactivity is critically involved in hypertension
pathophysiology; renal denervation (RDN) presents a novel strategy for treatment
of resistant hypertension cases. This study assessed effects of two RDN systems
to detect acute intravascular, vascular and peri-vascular changes in the renal
artery, and renal nerve alterations, in the sheep. The procedures using a single
point or multi-point ablation catheters, Symplicity Flex(TM), Medtronic versus
EnligHTN(TM), St. Jude Medical were compared; the intact contralateral kidneys
served as controls. Histopathological and immunohistochemical assessments were
performed 48 h after RDN procedures; the kidney and suprarenal gland morphology
was also evaluated. Special staining methods were applied for histologic
analysis, to adequately score the injury of renal artery and adjacent renal
nerves. These were more pronounced in the animals treated with the multi-point
compared with the single-point catheter. However, neither RDN procedure led to
complete renal nerve ablation. Forty-eight hours after the procedure no
significant changes in plasma and renal tissue catecholamines were detected. The
morphologic changes elicited by application of both RDN systems appeared to be
dependent on individual anatomical variability of renal nerves in the sheep.
Similar variability in humans may limit the therapeutic effectiveness of RDN
procedures used in patients with resistant hypertension.
PMID- 28406698
TI - Hematological profile of untreated or ionizing radiation-exposed cyclooxygenase-2
deficient mice.
AB - We investigated hematopoiesis in untreated and ionizing radiation-exposed
cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological
analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice
irradiated with the dose of 4 Gy of gamma-rays and their wildtype littermates. At
baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by
irradation in COX-2-deficient mice compared to wildtype. To conclude, the anti
inflammatory action of the COX-2 genetic disruption plays a positive role in
hematopoiesis under basal conditions but is detrimental following radiation
exposure.
PMID- 28406700
TI - Moderate exercise based on artificial gravity preserves orthostatic tolerance and
exercise capacity during short-term head-down bed rest.
AB - Numerous countermeasures have been proposed to minimize microgravity-induced
physical deconditioning, but their benefits are limited. The present study aimed
to investigate whether personalized aerobic exercise based on artificial gravity
(AG) mitigates multisystem physical deconditioning. Fourteen men were assigned to
the control group (n=6) and the countermeasure group (CM, n=8). Subjects in the
CM group were exposed to AG (2 Gz at foot level) for 30 min twice daily, during
which time cycling exercise of 80-95 % anaerobic threshold (AT) intensity was
undertaken. Orthostatic tolerance (OT), exercise tests, and blood assays were
determined before and after 4 days head-down bed rest (HDBR). Cardiac systolic
function was measured every day. After HDBR, OT decreased to 50.9 % and 77.5 % of
pre-HDBR values in control and CM groups, respectively. Exercise endurance,
maximal oxygen consumption, and AT decreased to 96.5 %, 91.5 % and 91.8 % of pre
HDBR values, respectively, in the control group. Nevertheless, there were slight
changes in the CM group. HDBR increased heart rate, sympathetic activity, and the
pre-ejection period, but decreased plasma volume, parasympathetic activity and
left-ventricular ejection time in the control group, whereas these effects were
eliminated in the CM group. Aldosterone had no change in the control group but
increased significantly in the CM group. Our study shows that 80-95 % AT aerobic
exercise based on 2 Gz of AG preserves OT and exercise endurance, and affects
body fluid regulation during short-term HDBR. The underlying mechanisms might
involve maintained cardiac systolic function, preserved plasma volume, and
improved sympathetic responses to orthostatic stress.
PMID- 28406701
TI - Prompt rise in urinary ammonium excretion suffices to mitigate metabolic acidosis
in an experimental animal model of severe normovolemic hemodilution.
AB - Recently, we have established a model of severe stepwise normovolemic
hemodilution to a hematocrit of 10 % in rats employing three different colloidal
volume replacement solutions (Voluven, Volulyte and Gelafundin) that are
routinely used in clinical practice at present. We did not see severe dilutional
acidosis as to be expected, but a decline in urinary pH. We here looked on
further mechanisms of renal acid excretion during normovolemic hemodilution.
Bicarbonate, which had been removed during normovolemic hemodilution, was
calculated with the help of the Henderson-Hasselbalch equation. The urinary
amount of ammonium as well as phosphate was determined in residual probes. The
absolute amount of free protons in urine was obtained from the pH of the
respective samples. The amount of protons generated during normovolemic
hemodilution was approximately 0.6 mmol. During experimental time (5.5 h),
distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39
mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer
constituted 0.04 mmol in every experimental group. Excretion of free protons was
in the range of 10(-6) mmol. The present data prove that the prompt rise in
urinary ammonium excretion is also valid for acute metabolic acidosis originating
from severe normovolemic hemodilution.
PMID- 28406702
TI - An alternatively activated macrophage marker CD163 in severely obese patients:
the influence of very low-calorie diet and bariatric surgery.
AB - CD163 is a marker of macrophages with anti-inflammatory properties and its
soluble form (sCD163) is considered a prognostic predictor of several diseases
including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline
and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with
obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with
T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We
also assessed the changes of CD163 positive cells of monocyte-macrophage lineage
in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients.
Plasma sCD163 levels were increased in obese and T2DM subjects relative to
control subjects (467.2+/-40.2 and 513.8+/-37.0 vs. 334.4+/-24.8 ng/ml, p=0.001)
and decreased after both interventions. Obesity decreased percentage of
CD163+CD14+ monocytes in peripheral blood compared to controls (78.9+/-1.48 vs.
86.2+/-1.31 %, p=0.003) and bariatric surgery decreased CD163+CD14+HLA-DR+
macrophages in SAT (19.4+/-2.32 vs. 11.3+/-0.90 %, p=0.004). Our data suggest
that increased basal sCD163 levels are related to obesity and its metabolic
complications. On the contrary, sCD163 or CD163 positive cell changes do not
precisely reflect metabolic improvements after weight loss.
PMID- 28406703
TI - Chronic administration of quercetin induces biomechanical and pharmacological
remodeling in the rat coronary arteries.
AB - Acute dilation brought about by the dietary flavonoid quercetin in coronary
arterioles has been described earlier, but no information is available on its
chronic effects. Male Wistar rats (body weight about 190 g) were divided to two
groups: the quercetin-treated group (n=22) had quercetin supplementation of
approximately 30 mg/kg/day, whereas the control group (n=20) had none. After
eight weeks of treatment, intramural coronary arterioles with identical passive
diameters (178+/-14 microm and 171+/-9 microm) were prepared and their
biomechanics and pharmacological reactivities were tested using pressure
arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was
higher (16.5+/-1.9 % vs. 12.9+/-0.9 %), which resulted in a reduced lumen size
(144+/-9 microm vs. 167+/-12 microm), thicker vascular wall (22.6+/-1.8 microm
vs. 17.4+/-1.6 microm) and decreased tangential wall stress (16.8+/-1.1 kPa vs.
20.5+/-1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01
in all these comparisons). Elevated basal NO release resulted in increased
endothelial dilation in quercetin-treated animals, especially at higher
intraluminal pressures (10.8+/-2.5 % vs. 5.7+/-1.3 % at 70 mm Hg, p<0.01). We
found remodeling of the geometry of coronary arterioles to ensure higher dilatory
reserve and nitrogen monoxide production, as well as lowered elastic stress of
the vessel wall.
PMID- 28406704
TI - Pro-inflammatory gene expression in adipose tissue of patients with
atherosclerosis.
AB - Inflammatory changes, both in the arterial wall and adipose tissue, play a
crucial role in the development of atherosclerosis. We measured the gene
expression of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant
protein-1 (MCP-1), and interleukin 6 (IL-6) in adipose tissue (AT) of living
kidney donors (LKD) and patients with peripheral arterial disease (PAD).
Quantitative polymerase chain reaction (qPCR) and flow cytometry analyses were
performed in subcutaneous (SAT), visceral (VAT), and perivascular adipose tissue
(PVAT). Data of PAD patients showed significantly higher expression in VAT in all
three genes (TNFalpha 5-fold, p<0.05; MCP-1 3.6-fold, p<0.05; IL-6 18.8-fold,
p<0.001). The differences in PVAT and SAT were less significant. Total body pro
inflammatory status was documented by higher TNFalpha concentration in patients
(4.86+/-1.4 pg/ml) compared to LKDs (2.14+/-0.9 pg/ml; p<0.001), as was hsCRP
(11.8+/-7.0 in PAD; 1.5+/-0.48 in LKDs; p=0.017). We found no age-dependent
relationship between gene expression vs. TNFalpha and hsCRP concentrations in
both compared groups. No effect of the atherosclerosis score on gene expression
and circulating inflammatory markers within the PAD group was observed. Our
results suggest that the AT of PAD patients infiltrated with macrophages produces
more cytokines involved in the development of inflammation and atherosclerosis.
PMID- 28406705
TI - Tolerance of isolated rabbit hearts to short ischemic periods is affected by
increased LV mass fraction.
AB - Hypertrophied hearts are known for increased risk of arrhythmias and are linked
with reduced ischemic tolerance. However, still little is known about state
characterized only by increased left ventricle (LV) mass fraction. Seventeen
isolated rabbit hearts with various LV mass were divided into two groups
according to LV weight/heart weight ratio (LVW/HW ratio), namely group H and L
(with higher and lower LVW/HW ratio, respectively) and underwent three short
cycles of global ischemia and reperfusion. The differences in electrogram (heart
rate, QRS(max), mean number, onset and dominant form of ventricular premature
beats) and in biochemical markers of myocardial injury (creatine kinase, lactate
dehydrogenase - LDH) and lipid peroxidation (4-hydroxy-2-nonenal - 4-HNE) were
studied. As compared to group L, hearts in group H exhibited lower tolerance to
ischemia expressed as higher incidence and severity of arrhythmias in the first
ischemic period as well as increase of LDH and 4-HNE after the first reperfusion.
In the third cycle of ischemia-reperfusion, the preconditioning effect was
observed in both electrophysiological parameters and LDH release in group H. Our
results showed consistent trends when comparing changes in electrograms and
biochemical markers. Moreover, 4-HNE seems to be good potential parameter of
moderate membrane alteration following ischemia-reperfusion injury.
PMID- 28406706
TI - Nanofat 2.0: experimental evidence for a fat grafting rich in mesenchymal stem
cells.
AB - Different strategies have been developed in the last decade to obtain fat grafts
as rich as possible of mesenchymal stem cells, so exploiting their regenerative
potential. Recently, a new kind of fat grafting, called "nanofat", has been
obtained after several steps of fat emulsification and filtration. The final
liquid suspension, virtually devoid of mature adipocytes, would improve tissue
repair because of the presence of adipose mesenchymal stem cells (ASCs). However,
since it is probable that many ASCs may be lost in the numerous phases of this
procedure, we describe here a novel version of fat grafting, which we call
"nanofat 2.0", likely richer in ASCs, obtained avoiding the final phases of the
nanofat protocol. The viability, the density and proliferation rate of ASCs in
nanofat 2.0 sample were compared with samples of nanofat and simple lipoaspirate.
Although the density of ASCs was initially higher in lipoaspirate sample, the
higher proliferation rate of cells in nanofat 2.0 virtually filled the gap within
8 days. By contrast, the density of ASCs in nanofat sample was the poorest at any
time. Results show that nanofat 2.0 emulsion is considerably rich in stem cells,
featuring a marked proliferation capability.
PMID- 28406707
TI - Moringa oleifera-rich diet and T cell calcium signaling in spontaneously
hypertensive rats.
AB - Moringa oleifera is a plant whose fruits, roots and leaves have been advocated
for traditional medicinal uses. The physicochemical analysis shows that Moringa
oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated
fatty acids (SFA). The consumption of an experimental diet enriched with Moringa
oleifera extracts lowered blood pressure in spontaneously hypertensive rats
(SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an
unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was
diminished in both strains of rats fed the Moringa oleifera. The experimental
diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with
rats fed the control diet. Studies of platelets from patients with primary
hypertension and from SHR support the notion that the concentration of
intracellular free calcium [Ca(2+)](i) is modified in both clinical and
experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T
cells of SHR than in those of WKY rats fed the control diet. Feeding the diet
with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T
cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that
Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of
IL-2 and modulates T cell calcium signaling in hypertensive rats.
PMID- 28406708
TI - Pack-Year Cigarette Smoking History for Determination of Lung Cancer Screening
Eligibility. Comparison of the Electronic Medical Record versus a Shared Decision
making Conversation.
AB - RATIONALE: Implementation of lung cancer screening programs is occurring across
the United States. Programs vary in approaches to patient identification and
shared decision-making. The eligibility of persons referred to screening
programs, the outcomes of eligibility determination during shared decision
making, and the potential for the electronic medical record (EMR) to identify
eligible individuals have not been well described. OBJECTIVES: Our objectives
were to assess the eligibility of individuals referred for lung cancer screening
and compare information extracted from the EMR to information derived from a
shared decision-making conversation for the determination of eligibility for lung
cancer screening. METHODS: We performed a retrospective analysis of individuals
referred to a centralized lung cancer screening program serving a five-hospital
health services system in Seattle, Washington between October 2014 and January
2016. Demographics, referral, and outcomes data were collected. A pack-year
smoking history derived from the EMR was compared with the pack-year history
obtained during a shared decision-making conversation performed by a licensed
nurse professional representing the lung cancer screening program. RESULTS: A
total of 423 individuals were referred to the program, of whom 59.6% (252 of 423)
were eligible. Of those, 88.9% (224 of 252) elected screening. There was 96.2%
(230 of 239) discordance in pack-year smoking history between the EMR and the
shared decision-making conversation. The EMR underreported pack-years of smoking
for 85.2% (196 of 230) of the participants, with a median difference of 29.2 pack
years. If identification of eligible individuals relied solely on the accuracy of
the pack-year smoking history recorded in the EMR, 53.6% (128 of 239) would have
failed to meet the 30-pack-year threshold for screening. CONCLUSIONS: Many
individuals referred for lung cancer screening may be ineligible. Overreliance on
the EMR for identification of individuals at risk may lead to missed
opportunities for appropriate lung cancer screening.
PMID- 28406709
TI - Long-Term Outcomes in a Population-based Cohort with Respiratory Nontuberculous
Mycobacteria Isolation.
AB - RATIONALE: The natural history of nontuberculous mycobacteria (NTM) respiratory
infection in the general population is poorly understood. OBJECTIVES: To describe
the long-term clinical, microbiologic, and radiographic outcomes of patients with
respiratory NTM isolates. METHODS: We previously identified a population-based
cohort of patients with respiratory NTM isolation during 2005-2006 and
categorized patients as cases or noncases using the American Thoracic
Society/Infectious Diseases Society of America pulmonary NTM disease criteria at
that time. During 2014-2015, we reviewed medical charts of patients alive on
January 1, 2007. Outcomes of interest were the proportion of baseline noncases
who later met case criteria and the proportions of patients with culture
conversion or findings consistent with persistent disease at least 2-5 years and
at least 5 years after first isolation. We defined disease persistence
radiographically as infiltrate, nodules, or cavities and microbiologically as a
positive respiratory mycobacterial culture. We used logistic regression to
evaluate factors associated with evidence of persistence. RESULTS: The study
included 172 patients (62% of 278 eligible); those not included either refused
consent (n = 47) or were not located (n = 56). One hundred two (59%) included
patients met case criteria at baseline. Mycobacterium avium complex was commonly
isolated among baseline cases (n = 91 [89%]) and noncases (n = 52 [74%]).
Overall, 57 (55%) baseline cases had died, as compared with 43 (61%) noncases (P
= 0.47). Among baseline noncases, only four (5.7%) later met case criteria.
Overall, 55 (54%) baseline cases and 6 (9%) noncases initiated NTM treatment.
Among cases, cultures were converted in 25 (64.1%) treated versus 4 (40%)
untreated patients (P = 0.04). Of 89 cases alive 2 years after isolation, 61
(69%) had additional radiography, and 35 (39%) had respiratory cultures. Of these
individuals, 54 (89%) had radiographic evidence and 17 (49%) had microbiologic
evidence of disease persistence. At 5 years after first isolation these figures
were 36 (82%) and 13 (54%), respectively. Women were more likely to have
persistent radiographic findings and microbiologic persistence, and patients with
chronic obstructive pulmonary disease were less likely to have microbiologic
persistence. CONCLUSIONS: In the general population, follow-up beyond 2 years of
patients with respiratory NTM isolation is limited. Among those with additional
evaluations, at least half of individuals have persistent positive cultures or
radiographic findings consistent with NTM at least 2 years after isolation.
PMID- 28406710
TI - Suboptimal Inspiratory Flow Rates Are Associated with Chronic Obstructive
Pulmonary Disease and All-Cause Readmissions.
AB - RATIONALE: Dry powder inhalers (DPIs) are prescribed after hospitalization for
acute exacerbation of COPD (AECOPD). Peak inspiratory flow (PIF) affects DPI
delivery. OBJECTIVES: To study the impact of PIF on readmission after
hospitalization for AECOPD. METHODS: A retrospective analysis of hospitalized
patients, enrolled in an AECOPD care plan, was performed. Data analyzed included
PIF, age, sex, length of stay, Charlson Comorbidity Index, COPD Assessment Test
score, modified Medical Research Council score, percent predicted FEV1, FVC, and
inspiratory capacity. A PIF equal to and less than 60 L/min was defined as
suboptimal (sPIF). Outcome measures included 30- and 90-day COPD and all-cause
readmissions, and days to next COPD and all-cause readmissions. RESULTS: Of the
123 subjects, 52% (n = 64) had sPIF. They had greater COPD Assessment Test scores
(29.1 +/- 5.9 vs. 25.3 +/- 8.7; P = 0.0073), rates of 90-day COPD readmissions
(28.1 vs. 13.6%; P = 0.048), fewer median days to COPD (63.5 [interquartile range
(IQR), 21-89.8] vs. 144 [IQR, 66-218]; P = 0.002) and all-cause readmissions
(65.5 [IQR, 24.3-107.3] vs. 101 [IQR, 54.5-205.5]; P = 0.009). PIF was the only
variable (P = 0.041) that predicted days to COPD readmission in a multivariate
model incorporating age, sex, percent predicted FEV1, Charlson Comorbidity Index,
and inspiratory flow group. In a group of patients with sPIF (n = 22), all-cause
and COPD 30- and 90-day readmission rates were significantly lower for those
discharged with nebulizer compared with DPI therapy. CONCLUSIONS: sPIF is common
during AECOPD and predicts all-cause and COPD readmissions. Patients with sPIF
may benefit from nebulized therapies. We recommend checking PIF in patients
hospitalized for AECOPD for selection of delivery devices.
PMID- 28406711
TI - Next Step to Understanding Subphenotypes of Acute Respiratory Distress Syndrome.
PMID- 28406712
TI - Reply: Next Step to Understanding Subphenotypes of Acute Respiratory Distress
Syndrome.
PMID- 28406713
TI - An Observational Study of Outcomes and Tolerances in Patients with Cystic
Fibrosis Initiated on Lumacaftor/Ivacaftor.
AB - RATIONALE: In July 2015, the U.S. Food and Drug Administration approved
lumacaftor/ivacaftor for use in patients with cystic fibrosis (CF). This drug
targets the primary defect in the CFTR protein that is conferred by the F508del
CFTR mutation. OBJECTIVE: As there is limited experience with this therapy
outside of clinical trials, this study aims to examine the clinical experience of
this new drug in a population with CF. RESULTS: Retrospective cohort study of
individuals followed at the Johns Hopkins CF Center who initiated treatment with
lumacaftor/ivacaftor. Patients were followed from 1 year before drug initiation
to up to 11 months postinitiation. Key exclusion criteria include previous
exposure to lumacaftor/ivacaftor through participation in a clinical trial. Of
116 individuals identified who started lumacaftor/ivacaftor treatment, 46 (39.7%)
reported adverse effects related to lumacaftor/ivacaftor, with the vast majority
(82.2%) being pulmonary adverse effects, and 20 (17.2%) discontinued
lumacaftor/ivacaftor because of adverse effects. The mean change in FEV1%
predicted was 0.11% (range: -39% to +20%; P = 0.9). Nineteen individuals had an
FEV1% predicted of 40% or less before treatment, and there was a higher
percentage of patients in this subgroup who reported adverse effects (57.9%) and
a higher percentage of patients who discontinued lumacaftor/ivacaftor (31.6%).
Female sex was associated with a higher odds of drug discontinuation (adjusted
odds ratio, 3.12, 95% confidence interval, 1.04-9.38). CONCLUSIONS: This study
highlights the prevalence of adverse effects in a CF population newly exposed to
lumacaftor/ivacaftor and demonstrates a relatively high rate of drug intolerance.
PMID- 28406714
TI - Clinical Outcomes Associated with Achromobacter Species Infection in Patients
with Cystic Fibrosis.
AB - RATIONALE: Achromobacter species are increasingly identified in individuals with
cystic fibrosis (CF), but the clinical outcomes in these patients remain poorly
understood. OBJECTIVES: We aimed to determine the association of Achromobacter
infection on clinical outcomes in pediatric and adult patients with CF. METHODS:
A cohort study of pediatric and adult patients with CF was conducted from 1997 to
2014 in Toronto, Ontario, Canada. Achromobacter spp. infection was categorized as
no history of infection, intermittent infection, and chronic infection (two or
more positive cultures in the preceding 12 months). Cox models were used to
estimate risk of death or transplantation. Mixed-effects models were used to
assess odds of pulmonary exacerbations and effect on lung function (FEV1%) by
Achromobacter spp. RESULTS: A total of 1,103 patients were followed-up over the
course of 18 years; 88 patients (7.3%) had one or more culture for Achromobacter
species. Chronic Achromobacter infection was associated with a greater risk of
death or transplantation compared with in patients with no history of infection
(adjusted hazard ratio, 2.03; 95% confidence interval, 1.05-3.95; P = 0.036).
Pulmonary exacerbations were more common in patients with chronic infection, but
after adjusting for confounding factors, the effect was no longer significant.
The chronic group had lower FEV1%, but it did not worsen after developing chronic
infection. CONCLUSIONS: Patients with CF and chronic Achromobacter infection are
at increased risk of death or transplantation.
PMID- 28406716
TI - Targeting Cyclin-Dependent Kinases in Ovarian Cancer.
AB - Ovarian cancer is the most common gynecological malignancy in the United States,
and prognosis is generally poor because the disease is often diagnosed at an
advanced stage. Cyclin-dependent kinases (CDKs) are a family of serine/threonine
kinases whose activity is regulated by CDK inhibitors (CKIs) and cyclins.
Generally, cyclins and CKIs promote and inhibit CDK activation, respectively.
Since cancer commonly involves dysregulation of cell cycle, cyclins and CDKs have
been targeted in a variety of tumors using small molecules, peptides,
immunotherapy, and CKIs. In this review we discuss the significance of cell cycle
dysregulation in ovarian cancer as well as recent advances targeting CDKs in
ovarian cancer and potential future directions. Although many of the studies
assessing CDK-targeting therapies in ovarian cancer are at an early preclinical
stage, there is significant evidence that targeting CDKs, particularly in
combination with traditional platinum-based drugs, could have significant
efficacy in ovarian cancer. Nevertheless, before these agents can be investigated
in humans, additional preclinical development is needed, including using in vivo
tumor models and additional studies into their mechanism of action.
PMID- 28406715
TI - Competitive endogenous RNA network: potential implication for systemic lupus
erythematosus.
AB - INTRODUCTION: Competitive endogenous RNA (ceRNA) hypothesis proposes that RNA
transcripts, both coding and non-coding, crosstalk with and coregulate each other
using microRNA response elements (MREs). CeRNA analysis tremendously expands
functional information of coding and non-coding RNAs. Mounting evidence have
shown that various types of RNAs, including pseudogenes, long non-coding RNAs,
circular RNAs, and messenger RNAs, can function as ceRNAs in distinct
physiological and pathophysiological states. Many validated ceRNA pairs
participate in the initiation and progression of cancers, and systemic ceRNA
network analyses revealing potential of ceRNAs in diagnosis, therapy, and
prognosis of cancers have also been performed. Areas covered: This review
concisely introduces ceRNA hypothesis and characteristics of ceRNA regulations.
The major sections focus on representative examples of both protein coding and
non-coding RNA transcripts acting as ceRNAs. CeRNA prediction programs and
databases and implications of ceRNA network in cancers are then discussed. In the
end, we surmise potential implications of ceRNA network for SLE. Expert opinion:
The role of ceRNA network in systemic lupus erythematosus (SLE) remains
undefined. We speculate that dissecting ceRNA network in SLE may help expand our
comprehension of roles of transcriptome, particularly non-coding transcripts, and
richen our knowledge of pathogenesis, diagnosis, and therapy of SLE.
PMID- 28406717
TI - Young steady-state rabbit platelets do not have an enhanced capacity to expose
procoagulant phosphatidylserine.
AB - Platelets are recognized to be physiologically and functionally heterogeneous. An
example of the diversity in reactivity is the formation of a distinct
subpopulation of procoagulant phosphatidylserine (PS)-exposing platelets upon
activation. Platelet age has been proposed as a determinant of platelet function,
and it has been reported that young platelets are more reactive in exposing PS;
using the same methodology of thiazole orange (TO) staining to distinguish young
and old platelets, the percentages of procoagulant platelets produced by thrombin
plus collagen activation of platelets from healthy controls were examined by flow
cytometry. The procoagulant subpopulation formed by TO-positive platelets (with
high TO fluorescence), purported to be young reticulated platelets, was observed
to be significantly larger than that formed by TO-negative platelets (with low TO
fluorescence), purported to be older platelets. However, it was noted that TO
fluorescence in the total platelet population was unimodal and increased with
platelet size, assessed by forward scatter. This observation raised the concern
that TO-positive platelets are not necessarily the youngest platelets in the
condition of steady-state platelet production. Thus, to unequivocally determine
whether platelet age is a factor in procoagulant platelet formation, a different
approach to identify young, steady-state platelets was employed. Rabbits were
injected with biotin to label >95% of circulating platelets in vivo; 24 hours
post-biotinylation, the non-biotinylated platelets in the circulation, detected
flow cytometrically, are the youngest, newly-formed platelets. It was
demonstrated that these youngest platelets were not larger in size than older,
biotinylated platelets, and that they did not have an enhanced capacity to expose
PS.
PMID- 28406718
TI - Pleural Touch Preparations and Direct Visualization of the Pleura during Medical
Thoracoscopy for the Diagnosis of Malignancy.
AB - RATIONALE: During diagnostic thoracoscopy, talc pleurodesis after biopsy is
appropriate if the probability of malignancy is sufficiently high. Findings on
direct visual assessment of the pleura during thoracoscopy, rapid onsite
evaluation (ROSE) of touch preparations (touch preps) of thoracoscopic biopsy
specimens, and preoperative imaging may help predict the likelihood of
malignancy; however, data on the performance of these methods are limited.
OBJECTIVES: To assess the performance of ROSE of touch preps, direct visual
assessment of the pleura during thoracoscopy, and preoperative imaging in
diagnosing malignancy. METHODS: Patients who underwent ROSE of touch preps during
thoracoscopy for suspected malignancy were retrospectively reviewed. Malignancy
was diagnosed on the basis of final pathologic examination of pleural biopsy
specimens. ROSE results were categorized as malignant, benign, or atypical cells.
Visual assessment results were categorized as tumor studding present or absent.
Positron emission tomography (PET) and computed tomography (CT) findings were
categorized as abnormal or normal pleura. Likelihood ratios were calculated for
each category of test result. RESULTS: The study included 44 patients, 26 (59%)
with a final pathologic diagnosis of malignancy. Likelihood ratios were as
follows: for ROSE of touch preps: malignant, 1.97 (95% confidence interval [CI],
0.90-4.34); atypical cells, 0.69 (95% CI, 0.21-2.27); benign, 0.11 (95% CI, 0.01
0.93); for direct visual assessment: tumor studding present, 3.63 (95% CI, 1.32
9.99); tumor studding absent, 0.24 (95% CI, 0.09-0.64); for PET: abnormal pleura,
9.39 (95% CI, 1.42-62); normal pleura, 0.24 (95% CI, 0.11-0.52); and for CT:
abnormal pleura, 13.15 (95% CI, 1.93-89.63); normal pleura, 0.28 (95% CI, 0.15
0.54). CONCLUSIONS: A finding of no malignant cells on ROSE of touch preps during
thoracoscopy lowers the likelihood of malignancy significantly, whereas finding
of tumor studding on direct visual assessment during thoracoscopy only moderately
increases the likelihood of malignancy. A positive finding on PET and/or CT
increases the likelihood of malignancy significantly in a moderate-risk patient
group and can be used as an adjunct to predict malignancy before pleurodesis.
PMID- 28406719
TI - Structured Expert Consensus on Actinic Keratosis: Treatment Algorithm Focusing on
Daylight PDT.
AB - BACKGROUND: A practical and up-to-date consensus among experts is paramount to
further improve patient care in actinic keratosis (AK). OBJECTIVES: To develop a
structured consensus statement on the diagnosis, classification, and practical
management of AK based on up-to-date information. METHODS: A systematic review of
AK clinical guidelines was conducted. This informed the preparation of a 3-round
Delphi procedure followed by a consensus meeting, which combined the opinions of
16 clinical experts from 13 countries, to construct a structured consensus
statement and a treatment algorithm positioning daylight photodynamic therapy (dl
PDT) among other AK treatment options. RESULTS: The systematic review found
deficiencies in current guidelines with respect to new AK treatments such as
ingenol mebutate and dl-PDT. The Delphi panel established consensus statements
across definition, diagnosis, classification, and management of AK. While the
diagnosis of AK essentially rests on the nature of lesions, treatment decisions
are based on several clinical and nonclinical patient factors and diverse
environmental attributes. Participants agreed on ranked treatment preferences for
the management of AK and on classifying AK in 3 clinical situations: isolated AK
lesions requiring lesion-directed treatment, multiple lesions within a small
field, and multiple lesions within a large field, both requiring specific
treatment approaches. Different AK treatment options were discussed for each
clinical situation. CONCLUSIONS: The results provide practical recommendations
for the treatment of AK, which are readily transferable to clinical practice, and
incorporate the physician's clinical judgement. The structured consensus
statement positioned dl-PDT as a valuable option for patients with multiple AKs
in small or large fields.
PMID- 28406720
TI - ?
PMID- 28406721
TI - ?
PMID- 28406722
TI - Development of quantitative monoclonal antibody-specific immobilization of
platelet antigens assay for antibodies against human platelet antigen-1a, 3a, and
5b.
AB - Human platelet antigens (HPAs) are platelet-specific alloantigens that cause
alloimmunization. Alloantibodies induced via pregnancy and transfusion may result
in various clinical syndromes. The monoclonal antibody-specific immobilization of
platelet antigens (MAIPA) assay is the gold standard for the detection and
identification of HPA antibodies. The present study aimed to develop standardized
quantitative MAIPA assays for antibodies against HPA-1a, 3a, and 5b. MAIPA
protocol was applied on serial dilutions of standard or reference reagents
containing antibodies against HPA-1a, 3a, and 5b. Optimal experimental parameters
were determined, and standard curves were constructed with a linear regression.
The sensitivity, specificity, and reproducibility of the assays were also
evaluated. The optimum reagents and conditions for the MAIPA assays were decided
through repeated testing and comparison. The intra-assay coefficients of
variation (CVs) are 1.3~3.6%, 2.7~5.2%, and 4.7~5.3%; the inter-assay CVs are
4.0~5.6%, 4.4~5.9%, and 3.2~6.3%, respectively, for HPA-1a, HPA-3a, and HPA-5b
antibodies. In specificity tests, some monoclonal antibodies and sera with other
antibodies were tested and no obvious positive result was observed. The
standardized quantitative MAIPA assays for antibodies against HPA-1a, 3a, and 5b
have good sensitivity, reproducibility, and specificity. They have important
application value in clinical diagnosis of alloimmunization disease caused by HPA
antibodies and safe transfusion of platelets.
PMID- 28406724
TI - Fifty Years of Research in ARDS. Gas Exchange in Acute Respiratory Distress
Syndrome.
AB - Acute respiratory distress syndrome (ARDS) is characterized by severe impairment
of gas exchange. Hypoxemia is mainly due to intrapulmonary shunt, whereas
increased alveolar dead space explains the alteration of CO2 clearance.
Assessment of the severity of gas exchange impairment is a requisite for the
characterization of the syndrome and the evaluation of its severity. Confounding
factors linked to hemodynamic status can greatly influence the relationship
between the severity of lung injury and the degree of hypoxemia and/or the
effects of ventilator settings on gas exchange. Apart from situations of rescue
treatment, targeting optimal gas exchange in ARDS has become less of a priority
compared with prevention of injury. A complex question for clinicians is to
understand when improvement in oxygenation and alveolar ventilation is related to
a lower degree or risk of injury for the lungs. In this regard, a full
understanding of gas exchange mechanism in ARDS is imperative for individualized
symptomatic support of patients with ARDS.
PMID- 28406725
TI - Flaxseed- and Buckwheat-Supplemented Diets Altered Enterobacteriaceae Diversity
and Prevalence in the Cecum and Feces of Obese Mice.
AB - Dietary intake may cause variable bacterial prevalence in the gastrointestinal
tract. The objective of this research was to determine the prevalence of
Enterobacteriaceae in the cecum and feces and its relationship to weight changes
following flaxseed-, health-promoting compounds of flaxseed-, or buckwheat
supplemented diets. Seventy-two C57BL/6J male mice were randomly assigned to a
diet group and fed for 8 weeks: high fat (45% kcal fat); 10% whole flaxseed (45%
kcal fat); 6% defatted flaxseed (45% kcal fat); 4% flaxseed oil (45% kcal fat);
10% buckwheat (45% kcal fat); and low fat (16% kcal fat) diet groups. Significant
differences in the prevalence of Enterobacteriaceae in the cecum (p < .0348) and
feces at posttreatment (p < .0033) were observed. The prevalence of
Enterobacteriaceae affected posttreatment weight (p < .0001). Our results
indicate that there may be a relationship between an increase in
Enterobacteriaceae prevalence and weight gain.
PMID- 28406723
TI - Aspirin Use and Colorectal Cancer Survival According to Tumor CD274 (Programmed
Cell Death 1 Ligand 1) Expression Status.
AB - Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint
pathway can improve clinical outcomes in various malignancies. Evidence suggests
that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only
prolongs colorectal cancer survival, but can also activate T cell-mediated
antitumor immunity and synergize with immunotherapy through inhibition of
prostaglandin E2 production. We hypothesized that the survival benefit associated
with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1
ligand 1, PD-L1) expression level that resulted in lower signaling of the immune
checkpoint pathway. Patients and Methods Using data from 617 patients with rectal
and colon cancer in the Nurses' Health Study and the Health Professionals Follow
Up Study, we examined the association of postdiagnosis aspirin use with patient
survival in strata of tumor CD274 expression status measured by
immunohistochemistry. We used multivariable Cox proportional hazards regression
models to control for potential confounders, including disease stage,
microsatellite instability status, CpG island methylator phenotype, long
interspersed nucleotide element-1 methylation, cyclooxygenase-2 (PTGS2), and CDX2
expression, and KRAS, BRAF, and PIK3CA mutations. Results The association of
postdiagnosis aspirin use with colorectal cancer-specific survival differed by
CD274 expression status ( Pinteraction < .001); compared with aspirin nonusers;
multivariable-adjusted hazard ratios for regular aspirin users were 0.16 (95% CI,
0.06 to 0.41) in patients with low CD274 and 1.01 (95% CI, 0.61 to 1.67) in
patients with high CD274. This differential association seemed consistent in
patients with microsatellite-stable or PIK3CA wild-type disease and in strata of
PTGS2 expression, CDX2 expression, tumor-infiltrating lymphocytes, or
prediagnosis aspirin use status. Conclusion The association of aspirin use with
colorectal cancer survival is stronger in patients with CD274-low tumors than
CD274-high tumors. Our findings suggest a differential antitumor effect of
aspirin according to immune checkpoint status.
PMID- 28406726
TI - Role of heterotrimeric G proteins in platelet activation and clot formation in
platelets treated with integrin alphaIIbbeta3 inhibitor.
AB - Mechanisms of platelet activation are triggered by thrombin, adenosine
diphosphate (ADP), epinephrine, thromboxane A2, and other soluble agonists which
induce signaling via heterotrimeric Galphaq, Galphai, and Galpha12/13 proteins.
We have undertaken a study addressing the contribution of these G proteins to
platelet activation and clot formation in the presence of eptifibatide, thus
excluding outside-in signaling provided by integrin alphaIIbbeta3-fibrinogen
engagement. Selective and combined activation of the G proteins was achieved by
using combinations of platelet agonists and inhibitors. Platelet activation in
platelet-rich plasma was evaluated by P-selectin expression using flow cytometry.
Contribution of platelets to whole blood clotting was assessed by rotation
thromboelastometry (ROTEM). Selective signaling of Galphaq or Galphai but not
Galpha12/13 promoted P-selectin expression. Further enhancement of P-selectin
expression was achieved by ADP-induced combined signaling of Galphaq and Galphai,
and to more extent by U46619 at high concentration (1.5 MUM) induced combined
signaling of Galphaq and Galpha12/13 while maximal P-selectin expression was
achieved by thrombin receptor-activating peptide (TRAP)-induced combined
signaling of Galphaq, Galphai, and Galpha12/13. In ROTEM, selective activation of
Galphaq, Galphai, or Galpha12/13 failed to affect blood clotting. Combined
signaling of Galphaq and Galphai or Galphaq and Galpha12/13 or all three G
proteins shortened the clotting time and stimulated clot strength. Pretreatment
of platelets with acetylsalicylic acid did not change the effect of ADP but
inhibited the effect of TRAP. Signaling of Galphaq and Galpha12/13 triggered by
U46619 also stimulated clot formation. Combined signaling of either Galphaq and
Galphai or Galphaq and Galpha12/13 is sufficient to stimulate maximal platelet
activation and enhanced clot formation in platelets treated with inhibitor of
integrin alphaIIbbeta3. It could be suggested that outside-in signaling is not
necessarily required to fulfill these platelet functions.
PMID- 28406727
TI - The Experience of Patients with Alcohol Misuse after Surviving a Critical
Illness. A Qualitative Study.
AB - RATIONALE: Alcohol misuse is common in patients admitted to the intensive care
unit (ICU), but there is currently no evidence-based approach to address drinking
in ICU survivors. OBJECTIVES: We sought to describe the experience of ICU
survivors with alcohol misuse during their hospitalization and the 3 months after
hospital discharge to inform an alcohol-specific intervention for this unique
population. METHODS: We conducted a descriptive qualitative study of ICU
survivors from medical ICUs in three separate hospitals with a positive screening
result on the Alcohol Use Disorders Identification Test. Semistructured
interviews were conducted 3 months after hospital discharge of patients. Patients
were also allowed to nominate up to two friends or family members for enrollment
to provide additional perspective on the patient's experience. RESULTS: We
enrolled 50 patients and 22 of their friends and/or family members. The average
APACHE II score was 23, 80% of patients were male, and the average age was 50
years; 70% of patients and 77% of friends/family members completed the
semistructured interview 3 months after hospital discharge. We identified three
domains that could inform an alcohol-specific intervention, each with multiple
themes: motivation with complications (anxiety and depression, critical illness
as a catalyst, delirium and cognitive impairment); therapeutic alliance
(autonomy, failure and opportunities to build a therapeutic alliance); and the
return to the home milieu (lack of screening for depression and anxiety, social
network support for drinking, social isolation, social network support for
abstinence, lack of available and affordable treatment, and negative experiences
with Alcoholics Anonymous). CONCLUSIONS: An alcohol intervention for ICU
survivors would account for the context in which patients are making a decision
about their drinking and optimize the patient-provider interaction. Contrary to
current paradigms that focus on addressing alcohol consumption only during a
hospitalization, an intervention for ICU survivors should continue as patients
transition from the hospital to home.
PMID- 28406728
TI - Clinical Evaluation of a Polyherbal Nutritional Supplement in Dyslipidemic
Volunteers.
AB - Ten important plant parts routinely used in South Indian ethnic food preparation
as spices and condiments were investigated for their potential antidyslipidemic
properties. The aim of the study was to characterize the biochemical properties
of the polyherbal formulation (nutritional supplement) and evaluate its use to
control dyslipidemia in patients. Phytochemical evaluation, in vitro alpha
amylase inhibitory assay, and high performance thin layer chromatography (HPTLC)
fingerprinting were carried out with alcoholic extracts of all 10 individual
plants and with the nutritional supplement. Investigation in human volunteers was
conducted to evaluate the effect on dyslipidemia as measured by serum lipid
biomarkers. Sixty-five volunteers were recruited for this study. Biomarker values
at baseline and at 6th visit (end of review, 8/9 months) were compared to assess
the usefulness of the nutritional supplement in the normalization of lipid
biomarkers. In the qualitative analysis of metabolites, the results revealed the
presence of various bioactive primary and secondary metabolites that might be
responsible for their medicinal attributes. In human volunteers, after supplement
intake along with standard therapy, we observed significant decrease in serum
cholesterol, triglyceride, low-density lipoprotein (LDL), and very low-density
lipoprotein (VLDL) levels. High-density lipoprotein (HDL) level did not change in
test patient volunteers. Reductions in hemoglobin A1C (HBA1C) and postprandial
blood sugar levels were observed; the difference was not statistically
significant. We believe that the polyherbal formulation of 10 medicinal plants
has potent antidyslipidemic activity. Our results contribute for the first time
toward documentation of augmented dyslipidemia control by use of the formulation.
PMID- 28406730
TI - Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology
Clinical Practice Guideline Update Summary.
PMID- 28406729
TI - Stabilization of the p53-DNA Complex by the Nuclear Protein Dmp1alpha.
AB - We recently reported the existence of a physical interaction between the Myb-like
transcription factor Dmp1 (Dmtf1) and p53 in which Dmp1 antagonized
polyubiquitination of p53 by Mdm2 and promoted its nuclear localization. Dmp1
significantly stabilized p53-DNA complexes on promoters that contained p53
consensus sequences, which were either supershifted or disrupted with antibodies
to Dmp1. Lysates from mice injected with doxorubicin showed that Dmp1 bound to
p21Cip1, Bbc3, and Thbs1 gene regulatory regions in a p53-dependent fashion. Our
data suggest that acceleration of DNA-binding of p53 by Dmp1 is a critical
process for Dmp1 to increase the p53 function in Arf-deficient cells.
PMID- 28406732
TI - Black Adzuki Bean (Vigna angularis) Attenuates High-Fat Diet-Induced Colon
Inflammation in Mice.
AB - Adzuki beans (Vigna angularis), one of the most important legume crops in East
Asia, have been shown to possess potential antioxidant and anti-inflammatory
effects in mice. Here, we investigated the effects of black adzuki bean (BAB) on
colon inflammation triggered by high-fat diet (HD)-induced obesity in mice. We
also isolated lipopolysaccharide (LPS)-stimulated peritoneal macrophages and
assessed inflammation-related parameters. We found that BAB decreased the
concentrations of LPS and various circulating proinflammatory cytokines such as
tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in mice with
HD-induced obesity. BAB also attenuated changes associated with HD-induced colon
inflammation, such as increased expression of proinflammatory cytokines.
Moreover, BAB inhibited induction of nitric oxide synthase (iNOS), cyclooxygenase
(COX)-2, and activation of nuclear factor-kappa B (NF-kappaB) in the colon.
Furthermore, BAB upregulated colon mRNA expression of tight junction-associated
proteins such as claudin-1 and Zo-1, as well as mucosal barrier defense promoting
genes such as mucin (Muc) 1 and Muc3. BAB also reduced macrophage infiltration
into adipose tissue in mice with HD-induced intestinal inflammation. In LPS
stimulated peritoneal macrophages, treatment with BAB significantly decreased TNF
alpha and NO production, NF-kappaB activation, and iNOS expression. Our findings
indicate that BAB ameliorates HD-induced disorders such as obesity and colitis by
improving mucosal barrier protection and reducing endotoxemia, as well as by
inactivating NF-kappaB to decrease the production of proinflammatory cytokines.
PMID- 28406731
TI - Protein Expression Level of Skin Wrinkle-Related Factors in Hairless Mice Fed
Hyaluronic Acid.
AB - The aim of this study was to evaluate the wrinkle improving effect of hyaluronic
acid intakes. Wrinkles were induced by exposing the skin of hairless mice to
ultraviolet B (UVB) irradiation for 14 weeks. Hyaluronic acid was administered to
the mice for 14 weeks including 4 weeks before experiments. Skin tissue was
assayed by enzyme-linked immunosorbent assay to determine protein expression of
wrinkle-related markers. The group supplemented with high concentrations of
hyaluronic acid appeared significantly better than control group for collagen,
matrix metalloproteinase 1, interleukin (IL)-1beta, and IL-6 assay. Transforming
growth factor-beta1 (TGF-beta1) and hyaluronic acid synthase 2 (HAS-2) were not
shown to be significantly different. In conclusion, hyaluronic acid
administration regulated expression levels of proteins associated with skin
integrity, and improved the wrinkle level in skin subjected to UVB irradiation.
PMID- 28406733
TI - Cerebrosides from Sea Cucumber Protect Against Oxidative Stress in SAMP8 Mice and
PC12 Cells.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder. Emerging evidence
implicates beta-amyloid (Abeta) plays a critical role in the progression of AD.
In this study, we investigated the protective effect of cerebrosides obtained
from sea cucumber against senescence-accelerated mouse prone 8 (SAMP8) mice in
vivo. We also studied the effect of cerebrosides on Abeta-induced cytotoxicity on
the rat pheochromocytoma cell (PC12) and the underlying molecular mechanisms.
Cerebrosides ameliorated learning and memory deficits and the Abeta accumulation
in demented mice, decreased the content of malondialdehyde (MDA), 8-oxo-7,8
dihydro-2'-deoxyguanosine (8-OHdG), 8-hydroxy-2'-deoxyguanosine (8-oxo-G), and
nitric oxide (NO), and enhanced the superoxide dismutase (SOD) activity
significantly. The neuroprotective effect of sea cucumber cerebrosides (SCC) was
also verified in vitro: the cerebrosides increased the survival rate of PC12
cells, recovered the cellular morphology, downregulated the protein levels of
Caspase-9, cleaved Caspase-3, total Caspase-3, and Bax, and upregulated the
protein level of Bcl-2, revealing that cerebrosides could inhibit Abeta-induced
cell apoptosis. The results showed the protective effect of SCC was regulated by
the mitochondria-dependent apoptotic pathway. Our results provide a new approach
to developing the marine organisms as functional foods for neuroprotection.
PMID- 28406734
TI - Effects of Trang Phuc Linh Plus-Food Supplement on Irritable Bowel Syndrome
Induced by Mustard Oil.
AB - Trang phuc linh plus (TPLP) is a food supplement product derived from dried
extracts of herbal agents Atractylodes macrocephala, Poria cocos, Paeonia
lactiflora, Phellodendron amurense, and added lactobacillus fermentum lysate
(ImmuneGamma(r)) and 5-hydroxytryptophan. TPLP is a functional food used as
adjunctive treatment for treating irritable bowel syndrome (IBS). However the
biological effect and its mechanism of action in IBS have not been elucidated. In
this study, we aimed to determine the pharmacological activities and mode of
action of TPLP on IBS animal models. Mice were given a single administration of
5% mustard oil (MO) intracollonically. Acute colitis induction by MO resulted in
later development of an IBS-like accelerated upper gastrointestinal transit in
mice. Mice were treated with different does of TPLP and controls. Results showed
that TPLP at the dose of 654 mg/kg/day given orally significantly decreased
intestinal motility (IM) compared with the control animals. The effect was
similar to Duspatalin (80 mg/kg/day) (Mebeverine Hydrochloride, an antispasmodic
that helps to relieve the pain and discomfort associated with gastrointestinal
spasms). Increased TPLP dose (1962 mg/kg/day) had a better effect on relief of IM
than Duspatalin (80 mg/kg/day). TPLP also reduced peristalsis frequency and
decreased fluid volume and electrolytes excretion in intestine tested in ex vivo
models. Overall, TPLP may be an effective nutraceutical supplement for IBS.
PMID- 28406735
TI - Capture-Recapture: Using Existing Data Sources to Improve Perinatal Hepatitis B
Surveillance, Philadelphia, 2008-2014.
AB - OBJECTIVE: The objective of this study was to describe the capture-recapture
method used by the Philadelphia Department of Public Health to enhance
surveillance of perinatal hepatitis B virus (HBV), report on results and
limitations of the process, and determine why some HBV-positive mother-infant
pairs were not initially identified by Philadelphia's Perinatal Hepatitis B
Prevention Program (PHBPP). METHODS: We performed capture-recapture
retrospectively for births in 2008 and 2009 in Philadelphia and prospectively for
births from 2010 to 2014 by independently matching annual birth certificate data
to PHBPP and HBV surveillance data. We compared the number of HBV-positive mother
infant pairs identified each year to the point estimates and lower-limit
estimates calculated by the Centers for Disease Control and Prevention for the
Philadelphia PHBPP. RESULTS: Of 156 605 pregnancy outcomes identified between
2008 and 2014, we found 1549 HBV-positive mother-infant pairs. Of 705 pairs that
were initially determined, 358 (50.7%) were confirmed to be previously
unidentified HBV-positive pairs. Reasons for failing to identify these mother
infant pairs prior to capture-recapture included internal administrative issues
(n = 191, 53.4%), HBV testing and reporting issues (n = 92, 25.7%), and being
lost to follow-up (n = 75, 20.9%). Each year that capture-recapture was used, the
number of pairs identified by the Philadelphia PHBPP exceeded the Centers for
Disease Control and Prevention's lower-limit estimates for HBV-positive mother
infant pairs. CONCLUSIONS: Capture-recapture was useful for identifying HBV
positive pregnant women for Philadelphia's PHBPP and for highlighting
inadequacies in health department protocols and HBV testing during pregnancy.
Other health departments with access to similar data sources and staff members
with the necessary technical skills can adapt this method.
PMID- 28406736
TI - Biofilm Formation on Aquaculture Substrates by Selected Bacterial Fish Pathogens.
AB - The objective of this study was to determine whether common bacterial catfish
pathogens could attach and colonize surfaces commonly found in aquaculture
facilities. In addition, we evaluated the role of calcium in biofilm formation.
Attachment to polystyrene plates was used to quantify biofilm formation by five
bacterial pathogens (i.e., Flavobacterium columnare, Aeromonas hydrophila,
Edwardsiella ictaluri, E. tarda, and E. piscicida). Flavobacterium columnare and
A. hydrophila formed thick biofilms that were enhanced by calcium
supplementation. Biofilm formation was significantly lower in all Edwardsiella
species tested and calcium had little to no effect on Edwardsiella biofilm
formation. Attachment to natural and artificial surfaces was quantified by a
standard plate count method. Scanning electron microscopy (SEM) was used to
confirm biofilm formation on the substrates. Flavobacterium columnare formed
biofilm on the liner, flexible PVC, and nets. Bamboo prevented F. columnare
attachment and inhibited cell growth. Aeromonas hydrophila and E. ictaluri formed
biofilm on all materials tested, although significant differences were found
among substrates. While E. ictaluri failed to form biofilm on microtiter
polystyrene plates, it was able to colonize and multiply on all aquaculture
materials tested. Our results demonstrated that common bacterial pathogens had
the potential of colonizing surfaces and may use biofilm as reservoirs in fish
farms. Received July 19, 2016; accepted January 19, 2017.
PMID- 28406737
TI - The overlooked dangers of anti-vaccination groups' social media presence.
PMID- 28406738
TI - Comparison of Gravity Flow Rates Between ENFit and Legacy Feeding Tubes.
AB - BACKGROUND: Misconnections between enteral supplies and other access devices have
led to significant morbidity and mortality. To reduce misconnections, a standard
small-bore connector has been developed (International Organization for Standards
80369-8; ENFit). The full impact of transition to this connector is not known,
however. METHOD: Working with major manufacturers and Food and Drug
Administration, we obtained ENFit and comparative legacy tubes of variable sizes
(low-profile, 14F, 18F, 20F, and 24F balloon gastrostomies). Gravity enteral
feeding was simulated with an empty bolus syringe attached to the feeding tube to
be tested. The tube was clamped and filled to the 60-mL mark with liquid (water,
Jevity 1 Cal, Isosource HN, Isosource 1.5 Cal, Two Cal HN, and Nourish). The
clamp was released, and time for formula to leave the syringe was recorded.
RESULTS: There was no difference in flow rate between the aggregate legacy and
ENFit tubes for the low-profile, 18F, and 20F sizes. The ENFit 14F tubes had a
lower flow rate versus the legacy tubes, largely due to the low flow rates seen
with the 1 ENFit tube. Similarly, 24F ENFit tubes with some formulas yielded
lower flow rates as opposed to legacy. CONCLUSION: Overall, for the low-profile,
18F, and 20F sizes, the ENFit tubes had similar flow rates when compared with the
legacy tubes. For the 14F and 24F sizes, the flow rate of ENFit tubes was
significantly lower, which could result in longer EN delivery for patients who
are using these tubes to provide gravity feeding.
PMID- 28406739
TI - Survey of contraindications in children's routine vaccination in Hangzhou, China.
AB - Objective To describe the epidemiological characteristics of contraindications in
children routine vaccination, to evaluate vaccination doctors' ability to
determine contraindications. Method Using cross-section study, 34 urban and 15
suburb units were selected from 206 Community Health Center (CHC) in Hangzhou,
China. Subjects were all children coming to CHCs for routine vaccination. All
situations considered to be unsuitable for vaccination were recorded as
contraindications. 3 experts were used to classify these abnormal records as true
or false contraindications. Then, the multi-analysis was used to find factors
related with the rate of false contraindications. Results There were 2801
children with 2969 contraindications in the present study. The prevalence of
contraindications was 3.030/00 by dose of vaccines. Cough (24.78%), fever
(21.86%) and medication (19.54%) were the most common contraindications in
children routine vaccination. Measles-rubella vaccine (MR) (6.780/00), measles
mumps-rubella vaccine (MMR) (5.870/00) and hepatitis B vaccine (Hep B) (5.250/00)
had higher prevalence of contraindications than other vaccines. According to the
evaluation of 3 experts, about 13.53% of contraindications were misdiagnosed by
vaccination doctor. The rate of misdiagnosed contraindications was correlated
with the sex, age and educational background of vaccination doctor, total dose of
vaccination of CHC. Conclusion A portion of children might miss the routine
vaccination because of misdiagnosed contraindications. More investigations are
needed to report the epidemiological distribution of contraindication in routine
vaccination of children.
PMID- 28406740
TI - alpha satellite DNA variation and function of the human centromere.
AB - Genomic variation is a source of functional diversity that is typically studied
in genic and non-coding regulatory regions. However, the extent of variation
within noncoding portions of the human genome, particularly highly repetitive
regions, and the functional consequences are not well understood. Satellite DNA,
including alpha satellite DNA found at human centromeres, comprises up to 10% of
the genome, but is difficult to study because its repetitive nature hinders
contiguous sequence assemblies. We recently described variation within alpha
satellite DNA that affects centromere function. On human chromosome 17 (HSA17),
we showed that size and sequence polymorphisms within primary array D17Z1 are
associated with chromosome aneuploidy and defective centromere architecture.
However, HSA17 can counteract this instability by assembling the centromere at a
second, "backup" array lacking variation. Here, we discuss our findings in a
broader context of human centromere assembly, and highlight areas of future study
to uncover links between genomic and epigenetic features of human centromeres.
PMID- 28406741
TI - Bridging the dynamics and organization of chromatin domains by mathematical
modeling.
AB - The genome is 3-dimensionally organized in the cell, and the mammalian genome DNA
is partitioned into submegabase-sized chromatin domains. Genome functions are
regulated within and across the domains according to their organization, whereas
the chromatin itself is highly dynamic. However, the details of such dynamic
organization of chromatin domains in living cells remain unclear. To unify
chromatin dynamics and organization, we recently demonstrated that structural
information of chromatin domains in living human cells can be extracted from
analyses of the subdiffusive nucleosome movement using mathematical modeling. Our
mathematical analysis suggested that as the chromatin domain becomes smaller and
more compact, nucleosome movement becomes increasingly restricted. Here, we show
the implication of these results for bridging the gap between chromatin dynamics
and organization, and provide physical insight into chromatin domains as
efficient units to conduct genome functions in the thermal noisy environment of
the cell.
PMID- 28406742
TI - Reading Disability Spectrum: Early and Late Recognition, Subthreshold, and Full
Comorbidity.
AB - Several studies have reported high comorbidity for reading disability (RD) and
psychiatric disorders. The aim of this study was to investigate the comorbidity
of subthreshold and full psychiatric disorders with RD while comparing subgroups
based on age of RD recognition (early vs. late). We analyzed data from 130
children with RD and 82 typically developing children aged 7 to 18 years. RD was
assessed with the Dyslexia Differential Diagnosis Maastricht-Hungarian Standard
Test. Psychiatric diagnoses were based on the Mini International Neuropsychiatric
Interview Kid. Chi-square tests were used for group comparisons of the prevalence
of subthreshold and full disorders. A higher proportion of children in the RD
group were assessed as having internalizing or externalizing disorders. When
subthreshold and full diagnoses were considered together, the prevalence of
internalizing but not externalizing pathology was higher in the RD group than the
control group. The prevalence of internalizing pathology was similar in the early
and late RD subgroups, but externalizing pathology was more common in the late RD
subgroup. When subthreshold and full diagnoses were considered together, mood
disorder and externalizing pathology were more prevalent in the late RD subgroup
than the early RD subgroup. This study demonstrated that early recognition of RD
may play a role in determining comorbid psychopathology and should therefore be
an educational and clinical priority. Clinicians should routinely screen children
with RD for comorbid disorders, including subthreshold pathology.
PMID- 28406744
TI - Comparing Students With and Without Reading Difficulties on Reading Comprehension
Assessments: A Meta-Analysis.
AB - Researchers have increasingly investigated sources of variance in reading
comprehension test scores, particularly with students with reading difficulties
(RD). The purpose of this meta-analysis was to determine if the achievement gap
between students with RD and typically developing (TD) students varies as a
function of different reading comprehension response formats (e.g., multiple
choice, cloze). A systematic literature review identified 82 eligible studies.
All studies administered reading comprehension assessments to students with RD
and TD students in Grades K-12. Hedge's g standardized mean difference effect
sizes were calculated, and random effects robust variance estimation techniques
were used to aggregate average weighted effect sizes for each response format.
Results indicated that the achievement gap between students with RD and TD
students was larger for some response formats (e.g., picture selection ES g =
1.80) than others (e.g., retell ES g = -0.60). Moreover, for multiple-choice,
cloze, and open-ended question response formats, single-predictor metaregression
models explored potential moderators of heterogeneity in effect sizes. No clear
patterns, however, emerged in regard to moderators of heterogeneity in effect
sizes across response formats. Findings suggest that the use of different
response formats may lead to variability in the achievement gap between students
with RD and TD students.
PMID- 28406743
TI - The "readers" of unacetylated p53 represent a new class of acidic domain
proteins.
AB - Acetylation of non-histone proteins plays important roles in regulating protein
functions but the mechanisms of action are poorly understood. Our recent study
uncovered a previously unknown mechanism by which C-terminal domain (CTD)
acetylation of p53 serves as a "switch" to determine the interaction between a
unique group of acidic domain-containing proteins and p53, as well as revealed
that acidic domains may act as a novel class of "readers" for unacetylated p53.
However, the properties of acidic domain "readers" are not well elucidated yet.
Here, we identified that the charge effect between acidic domain "readers" and
the p53 CTD is necessary for their interaction. Both the length and the amino
acid composition of a given acidic domain contributed to its ability to recognize
the p53 CTD. Finally, we summarized the characteristic features of our identified
acidic domains, which would distinguish this kind of "readers" from other types
of acidic amino acid-containing domains.
PMID- 28406745
TI - Measured carbon monoxide concentrations from stock and reduced-emission prototype
portable generators operated in an attached garage.
AB - : There is concern about the hazard of acute residential CO exposures from
portable gasoline-powered generators, which can result in death or serious
adverse health effects in exposed individuals. To address this hazard, the U.S.
Consumer Product Safety Commission has developed low CO emission prototype
generators by adapting off-the-shelf emission control technologies onto
commercially available generators. A series of tests was conducted to
characterize the indoor CO concentrations resulting from portable generators
operating in the attached garage of a research house under seven different test
house/garage configurations. The tested generators include both unmodified and
modified low CO emission prototypes. It was found that CO concentrations varied
widely, with peak house CO concentrations ranging from under 10 ppm to over
10,000 ppm. The highest concentrations in the house resulted from operation of
the unmodified generator in the garage with the garage bay door closed and the
house access door open. The lowest concentrations resulted from operation of a
modified low CO emission prototype in the garage with the garage bay door open
and the house access door closed. These tests documented reductions of up to 98%
in CO concentrations due to emissions from two low CO emission portable
generators compared to a stock generator. IMPLICATIONS: Improper portable
generator use has caused 800 U.S. deaths in the past 14 years. Generators
operated in attached garages can cause CO to quickly reach deadly levels. Two low
emission prototypes generators were tested and had CO emissions reduced by up to
98%. Low-emission generators can reduce the risk of consumer poisonings and
deaths.
PMID- 28406747
TI - 100 Years of Radiation Research in the Footsteps of Failla.
AB - Gioacchino Failla was initially appointed to operate the radon plant at Memorial
Hospital in 1916. What to most people would have been a part-time temporary
position was to him a career. He was not satisfied to simply fabricate radon
seeds, he wanted to understand the physics and biology of the radiation emitted
by the progeny of radium. His was not the first medical physics group in the
United States, though it was one of the earliest, but it was the first to put
such emphasis on the biological effects. After more than 28 years at Memorial
Hospital, Failla moved his research group to Columbia University Medical Center
and his pioneering work, blending physics and biology, has continued to date at
Columbia by those that he trained or inspired, under three directors that
followed him.
PMID- 28406746
TI - Immunogenicity and safety of a cell culture-derived inactivated quadrivalent
influenza vaccine (NBP607-QIV): A randomized, double-blind, multi-center, phase
III clinical trial in adults and elderly subjects.
AB - BACKGROUND: The influenza B virus has two lineages; Yamagata and Victoria. The
two lineages are antigenically distinct and it is difficult to expect cross
protection between the lineages. Actually, the mismatch between circulating
influenza B viruses and vaccine strains has been occurred frequently. The cell
culture system for the production of influenza vaccine can contribute to improve
vaccine strain selection and expand vaccine supplies. We investigated the
immunogenicity and safety of cell culture-derived quadrivalent inactivated
influenza vaccine (NBP607-QIV) in adults and elderly subjects. METHODS: A
randomized controlled phase III trial was undertaken in 10 university hospitals
in the Republic of Korea (Clinical trial Number-NCT02467842). Adults (aged 19-59
years) and elderly subjects (aged >=60 years) were randomly assigned in a 2:1:1
ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza
vaccine-Yamagata (NBP607-Y) and cell culture-based trivalent inactivated
influenza vaccine-Victoria (NBP607-V). Immunogenicity was assessed 3 weeks after
vaccination by hemagglutination inhibition assay. Safety was assessed for 6
months post-vaccination: solicited adverse events (AEs) for 7 days, unsolicited
AEs for 21 days and serious adverse events (SAEs) for 6 months. AEs were sub
classified as adverse drug reactions (ADRs) according to the causality. RESULTS:
A total of 1,503 participants were randomly assigned to NBP607-QIV (n = 752),
NBP607-Y (n = 373) and NBP607-V (n = 378). The seroconversion rates of NBP607-QIV
were 52.4%, 51.2%, 43.7% and 55.8% against A/H1N1, A/H3N2, B/Yamagata and
B/Victoria, respectively. Non-inferiority against shared strains and superiority
against alternate-lineage B strains were demonstrated for NBP607-QIV vs. NBP607-Y
and NBP607-V. A total of 730 reactions occurred in 324 (43.1%) subjects of NBP607
QIV group. Majority of ADRs was solicited (99.2%) and mild (90.3%) in intensity.
In adults (aged 19-59 years), solicited local AEs were slightly more frequent in
NBP607-QIV group than NBP607-Y or NBP607-V group (40.9%, 33.4% and 32.5%,
respectively). One SAE was observed among NBP607-QIV group, which was considered
to be unrelated to the study vaccine within 3 weeks of vaccination and no vaccine
related SAEs were reported up to 6 months after vaccination. CONCLUSIONS: NBP607
QIV is a safe, well-tolerated and immunogenic influenza vaccine in Korean adults
and elderly subjects.
PMID- 28406748
TI - Radiation-Induced Dermatitis is Mediated by IL17-Expressing gammadelta T Cells.
AB - Radiation dermatitis is a serious cutaneous injury caused by radiation therapy or
upon accidental nuclear exposure. However, the pathogenic immune mechanisms
underlying this injury are still poorly understood. We seek to discover how the
dysregulated immune response after irradiation orchestrates skin inflammation.
The skin on the left flank of C57BL/6J wild-type and C57BL/6J Tcrd-/- mice, which
are deficit in gammadelta T cells, was exposed to a single X-ray dose of 25 Gy,
and the right-flank skin was used as a sham-irradiated control. At 4 weeks
postirradiation, the wild-type skin exhibited signs of depilation, erythema and
desquamation. Histological analysis showed hyperproliferation of keratinocytes
and acanthosis. Dramatic elevation of IL17-expressing T cells was identified from
the irradiated skin, which was mainly contributed by gammadelta T cells and
innate lymphoid cells, rather than Th17 cells. Furthermore, protein levels of
critical cytokines for IL17-expressing gammadelta T cell activation, IL1beta and
IL23 were found markedly upregulated. Lastly, radiation-induced dermatitis was
significantly attenuated in gammadelta T cell knockout mice. In vitro, normal
human epidermal keratinocytes (NHEKs) could be initiator cells of inflammation by
providing a great number of pro-inflammatory mediators upon radiation, and as
well as effector cells of epidermal hyperplasia in response to exogenous IL17
and/or IL22 treatment. Our findings implicate a novel role of IL17-expressing
gammadelta T cells in mediating radiation-induced skin inflammation. This study
reveals the innate immune response pathway as a potential therapeutic target for
radiation skin injury.
PMID- 28406749
TI - Nucleosome repositioning during differentiation of a human myeloid leukemia cell
line.
AB - Cell differentiation is associated with changes in chromatin organization and
gene expression. In this study, we examine chromatin structure following
differentiation of the human myeloid leukemia cell line (HL-60/S4) into
granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA).
We performed ChIP-seq of histone H3 and its modifications, analyzing changes in
nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin
redistribution and properties of epichromatin (surface chromatin adjacent to the
nuclear envelope). Nucleosome positions changed genome-wide, exhibiting a
specific class of alterations involving nucleosome loss in extended (~1kb)
regions, pronounced in enhancers and promoters. Genes that lost nucleosomes at
their promoters showed a tendency to be upregulated. On the other hand,
nucleosome gain did not show simple effects on transcript levels. The average
genome-wide nucleosome repeat length (NRL) did not change significantly with
differentiation. However, we detected an approximate 10 bp NRL decrease around
the haematopoietic transcription factor (TF) PU.1 and the architectural protein
CTCF, suggesting an effect on NRL proximal to TF binding sites. Nucleosome
occupancy changed in regions associated with active promoters in differentiated
cells, compared with untreated HL-60/S4 cells. Epichromatin regions revealed an
increased GC content and high nucleosome density compared with surrounding
chromatin. Epichromatin showed depletion of major histone modifications and
revealed enrichment with PML body-associated genes. In general, chromatin changes
during HL-60/S4 differentiation appeared to be more localized to regulatory
regions, compared with genome-wide changes among diverse cell types studied
elsewhere.
PMID- 28406750
TI - Sirtuins and DNA damage repair: SIRT7 comes to play.
AB - Aging is characterized by a cumulative loss of genome integrity, which involves
chromatin reorganization, transcriptional dysregulation and the accumulation of
DNA damage. Sirtuins participate in the protection against these aging processes
by promoting genome homeostasis in response to cellular stress. We recently
reported that SirT7-/- mice suffer from partial embryonic lethality and a
progeroid like phenotype. At the cellular level, SIRT7 depletion results in the
impaired repair of DNA double-strand breaks (DSBs), one the most dangerous DNA
lesions, leading to genome instability. SIRT7 is recruited to DSBs, where it
specifically deacetylates histone H3 at lysine 18 and affects the focal
accumulation of the DNA damage response factor 53BP1, thus influencing the
efficiency of repair. Here, we integrate our findings with the current knowledge
on the mode of action of other sirtuin family members in DNA repair. We emphasize
their capacity to regulate chromatin structure as a response to DNA damage within
the constraints imposed by cellular status.
PMID- 28406752
TI - Comparison of the immunogenicity and safety of the purified chick embryo cell
rabies vaccine manufactured in India and Germany: A randomized, single blind,
multicentre, phase IV clinical study.
AB - This phase IV, single blind study assessed the immunogenicity and safety of India
manufactured purified chick embryo cell rabies vaccine (PCECV), compared with a
German-manufactured batch obtained by the same production process. A total of 340
participants enrolled at 2 study sites in India were randomized (1:1:1:1) in 4
groups to receive a 5-dose Essen regimen with either 1 of the 3 Indian batches
(PCECV-I) or the German batch (PCECV-G), administered on Days (D) 0, 3, 7, 14 and
30. The lot-to-lot consistency of PCECV-I batches in terms of induced immune
response at D14 was demonstrated. The immune response elicited by PCECV-I was
shown to be non-inferior to that induced by PCECV-G, as the lower limit of the
95% confidence interval for the ratio (PCECV-I/PCECV-G) of rabies virus
neutralising antibody (RVNA) geometric mean concentrations was higher than 0.5 at
D14. At least 96% of participants developed adequate RVNA concentrations (>= 0.5
IU/mL) by D14 and all achieved RVNA concentrations >= 0.5 IU/mL by D90. RVNA
levels were comparable across all groups throughout the entire study. Solicited
local and general symptoms had a similar incidence in all groups. Unsolicited
adverse events (AEs) were reported by 11% of participants. Only 1 serious AE (leg
fracture) was reported and was not related to vaccination. No deaths and no
rabies cases were recorded during the 90 days of observation. The study showed
that the 3 PCECV-I and the PCECV-G batches induced a similar immune response and
had a comparable safety profile when administered according to a 5-dose schedule.
PMID- 28406751
TI - Repetitive DNA loci and their modulation by the non-canonical nucleic acid
structures R-loops and G-quadruplexes.
AB - Cells have evolved intricate mechanisms to maintain genome stability despite
allowing mutational changes to drive evolutionary adaptation. Repetitive DNA
sequences, which represent the bulk of most genomes, are a major threat to genome
stability often driving chromosome rearrangements and disease. The major source
of repetitive DNA sequences and thus the most vulnerable constituents of the
genome are the rDNA (rDNA) repeats, telomeres, and transposable elements.
Maintaining the stability of these loci is critical to overall cellular fitness
and lifespan. Therefore, cells have evolved mechanisms to regulate rDNA copy
number, telomere length and transposon activity, as well as DNA repair at these
loci. In addition, non-canonical structure-forming DNA motifs can also modulate
the function of these repetitive DNA loci by impacting their transcription,
replication, and stability. Here, we discuss key mechanisms that maintain rDNA
repeats, telomeres, and transposons in yeast and human before highlighting
emerging roles for non-canonical DNA structures at these repetitive loci.
PMID- 28406753
TI - Assessing the Effect of Preoperative Nutrition on Upper Body Function in Elderly
Patients Undergoing Elective Abdominal Surgery.
AB - BACKGROUND: Malnutrition among elderly surgical patients has been associated with
poor postoperative outcomes and reduced functional status. Although previous
studies have shown that nutrition contributes to patient outcomes, its long-term
impact on functional status requires better characterization. This study examines
the effect of nutrition on postoperative upper body function over time in elderly
patients undergoing elective surgery. METHODS: This is a 2-year prospective study
of elderly patients (>=70 years) undergoing elective abdominal surgery.
Preoperative nutrition status was determined with the Subjective Global
Assessment (SGA). The primary outcome was handgrip strength (HGS) at 1, 4, 12,
and 24 weeks postsurgery. Repeated measures analysis was used to determine
whether SGA status affects the trajectory of postoperative HGS. RESULTS: The
cohort included 144 patients with a mean age of 77.8 +/- 5.0 years and a mean
body mass index of 27.7 +/- 5.1 kg/m2. The median (interquartile range) Charlson
Comorbidity Index was 3 (2-6). Participants were categorized as well-nourished
(86%) and mildly to moderately malnourished (14%), with mean preoperative HGS of
25.8 +/- 9.2 kg and 19.6 +/- 7.0 kg, respectively. At 24 weeks, 64% of well
nourished patients had recovered to baseline HGS, compared with 44% of mildly to
moderately malnourished patients. Controlling for relevant covariates, SGA did
not significantly affect the trajectory of postoperative HGS. CONCLUSION: While
HGS values over the 24 weeks were consistently higher in the well-nourished SGA
group than the mildly to moderately malnourished SGA group, no difference in the
trajectories of HGS was detected between the groups.
PMID- 28406755
TI - A Modified Hydroxyproline Assay Based on Hydrochloric Acid in Ehrlich's Solution
Accurately Measures Tissue Collagen Content.
AB - Collagen quantification has long been relevant to biomedical research and
clinical practice to characterize tissues and determine disease states. The
hydroxyproline assay, while a broadly employed method of quantifying collagen,
uses perchloric acid to dissolve Ehrlich's reagent. Since perchloric acid poses
occupational safety hazards and high costs, in this study, a new hydroxyproline
assay was developed that replaces perchloric acid with a relatively safer and
cheaper alternative, hydrochloric acid (HCl). To validate this biochemical
technique, first, using either acid to dissolve Ehrlich's reagent, the assays
were completed for native and engineered collagenous tissues. No statistical
differences were identified between the assays (p = 0.32). Subsequently, both
biochemical techniques were compared to amino acid analysis, considered a
proteomics gold standard. Interestingly, utilizing HCl in lieu of perchloric acid
yielded greater concordance with amino acid analysis (rhoc = 0.980) than did the
traditional assay (rhoc = 0.947); that is, the HCl-based assay more closely
estimates hydroxyproline content, and, consequently, true collagen content. Thus,
using Ehrlich's reagent containing HCl in the hydroxyproline assay represents an
advance in both mitigating laboratory safety hazards and improving biochemical
collagen quantification.
PMID- 28406756
TI - Myocardial Necrosis Associated with Clostridium novyi Infection in a Bighorn
Sheep ( Ovis canadensis ).
AB - We describe a case of myocardial emphysema and necrosis in a bighorn sheep ( Ovis
canadensis ), associated with infection by Clostridium novyi , diagnosed through
necropsy, histopathology, and fluorescent antibody testing. We documented rapid
onset of disease in an apparently healthy wild sheep and discuss our findings in
the context of reported clostridial infections in humans, domestic animals, and
wildlife.
PMID- 28406754
TI - Spheroid Coculture of Hematopoietic Stem/Progenitor Cells and Monolayer Expanded
Mesenchymal Stem/Stromal Cells in Polydimethylsiloxane Microwells Modestly
Improves In Vitro Hematopoietic Stem/Progenitor Cell Expansion.
AB - While two-dimensional (2D) monolayers of mesenchymal stem/stromal cells (MSCs)
have been shown to enhance hematopoietic stem/progenitor cell (HSPC) expansion in
vitro, expanded cells do not engraft long term in human recipients. This outcome
is attributed to the failure of 2D culture to recapitulate the bone marrow (BM)
niche signal milieu. Herein, we evaluated the capacity of a novel three
dimensional (3D) coculture system to support HSPC expansion in vitro. A high
throughput polydimethylsiloxane (PDMS) microwell platform was used to manufacture
thousands of uniform 3D multicellular coculture spheroids. Relative gene
expression in 3D spheroid versus 2D adherent BM-derived MSC cultures was
characterized and compared with literature reports. We evaluated coculture
spheroids, each containing 25-400 MSCs and 10 umbilical cord blood (CB)-derived
CD34+ progenitor cells. At low exogenous cytokine concentrations, 2D and 3D MSC
coculture modestly improved overall hematopoietic cell and CD34+ cell expansion
outcomes. By contrast, a substantial increase in CD34+CD38- cell yield was
observed in PDMS microwell cultures, regardless of the presence or absence of
MSCs. This outcome indicated that CD34+CD38- cell culture yield could be
increased using the microwell platform alone, even without MSC coculture support.
We found that the increase in CD34+CD38- cell yield observed in PDMS microwell
cultures did not translate to enhanced engraftment in NOD/SCID gamma (NSG) mice
or a modification in the relative human hematopoietic lineages established in
engrafted mice. In summary, there was no statistical difference in CD34+ cell
yield from 2D or 3D cocultures, and MSC coculture support provided only modest
benefit in either geometry. While the high-throughput 3D microwell platform may
provide a useful model system for studying cells in coculture, further
optimization will be required to generate HSPC yields suitable for use in
clinical applications.
PMID- 28406757
TI - Rabies Virus Exposure of Brazilian Free-ranging Wildlife from Municipalities
without Clinical Cases in Humans or in Terrestrial Wildlife.
AB - Rabies is a zoonosis that causes thousands of animal and human deaths worldwide.
Serological studies provide information concerning rabies virus circulation among
animals and humans. We evaluated the circulation of the rabies virus in wildlife
in nine municipalities of Sao Paulo State, Brazil. We took blood samples from 27
terrestrial animals of nine different mammalian species in locations without
cases of rabies in human and wild terrestrial mammals. Sera were tested with the
use of the rapid fluorescent focus inhibition test (RFFIT) for the detection of
rabies virus-neutralizing antibodies (RVNA). The RFFIT was positive in 100% of
the samples, with many (81.48%) showing protective titer levels (>0.5 IU/mL) with
other samples (18.52%) showing titers representing exposure (<0.5 IU/mL). We
report RVNA in novel species (e.g., Alouatta caraya and Tapyrus terrestris). Wild
animals were exposed to rabies virus in municipalities without a history of human
rabies cases, which demonstrated a need for research to understand the role of
these animals in the circulation and transmission of the disease.
PMID- 28406758
TI - Fasting triglycerides as a predictor of incident diabetes, insulin resistance and
beta-cell function in a Canadian First Nation.
AB - BACKGROUND: Diabetes prevalence is substantially higher among Canadian First
Nations populations than the non-First Nation population. Fasting serum
triglycerides have been found to be an important predictor of incident diabetes
among non-indigenous populations. However, there is a great need to understand
diabetes progression within specific ethnic groups, particularly First Nations
populations. OBJECTIVE: The purpose of this study was to test for an association
between fasting serum triglycerides and incident diabetes, changes in insulin
resistance and changes in beta-cell function in a Manitoba First Nation cohort.
METHODS: Study data were from two diabetes screening studies in Sandy Bay First
Nation in Manitoba, Canada, collected in 2002/2003 and 2011/2012. The cohort was
composed of respondents to both screening studies (n=171). Fasting blood samples
and anthropometric, health and demographic data were collected. A generalised
linear model with Poisson distribution was used to test for an association
between fasting triglycerides and incident diabetes. RESULTS: There were 35
incident cases of diabetes among 128 persons without diabetes at baseline.
Participants who developed incident type 2 diabetes were significantly older and
had significantly higher body mass index (BMI; p=0.012), total cholesterol
(p=0.007), fasting triglycerides (p<0.001), and Homeostatic Model Assessment of
Insulin Resistance (HOMA-IR) (p<0.001). Fasting triglyceride level was found to
be a statistically significant positive predictor of incident diabetes
independent of age, sex and waist circumference at baseline. Participants with
triglycerides in the highest tertile (>=2.11 mmol/l) had a 4.0-times higher risk
of developing incident diabetes compared to those in the lowest tertile (p=0.03).
Notably, neither waist circumference nor BMI were significant predictors of
incident diabetes independent of age, sex and triglycerides. CONCLUSION: Fasting
triglycerides may be useful as a clinical predictor of insulin resistance and
diabetes development among First Nations populations. Unlike other ethnic groups,
BMI and waist circumference may be less important factors in diabetes
development.
PMID- 28406760
TI - Adherence to guidelines for the treatment of Behcet's syndrome in New York and
Amsterdam.
AB - OBJECTIVES: To assess adherence to published guidelines for the treatment of
Behcet's syndrome (BS) in two geographic areas. METHODS: We extracted guideline
statements from the 2008 EULAR recommendations. Adherence to these statements was
evaluated retrospectively in both New York (USA) and Amsterdam (The Netherlands),
by reviewing records from patients fulfilling the ISG criteria. We analysed data
per statement and event, and divided data according to the year in which an event
occurred. We compared events prior to 2009 to those after publication of the
EULAR recommendations (2009 and later). RESULTS: 474 patients were evaluated, 24
of whom were from Amsterdam. Treatment adherence varied substantially across
various Behcet's manifestations, ranging from 21% vs. 31% in posterior uveitis,
50% vs. 25% in arterial disease, 29% vs. 29% in arthritis and 38% vs. 55% in
erythema nodosum to 65% vs. 67% in deep venous thrombosis (DVT), before and after
publication of the guidelines respectively. Topical treatment of mucocutaneous
disease was only 2% vs. 8%, whereas adherence in neuro-Behcet was >= 94% and 100%
in gastrointestinal disease. CONCLUSIONS: Adherence to treatment guidelines
varies substantially by Behcet's manifestation. Lack of adherence in
manifestations such as eye disease and arthritis suggests that current
recommendations are not sufficient or other concurrent manifestations require
more aggressive treatment. The extensive use of anti-TNF agents might indicate a
shift towards more aggressive treatment. Thus, our results suggest the 2008
guidelines were not in line with treatment in clinical practice over the past
years and the recent revision of the recommendations was indeed needed.
PMID- 28406761
TI - The performance of different classification criteria in paediatric Behcet's
disease.
AB - OBJECTIVES: Behcet's disease (BD) is a variable vessel vasculitis. The most
widely used classification criteria for adults is the International Behcet's
Study Group (ISG) criteria. Recently, the paediatric BD (PEDBD) classification
criteria has been developed for children. For disease activity, there are mainly
two severity scores; the Iranian BD dynamic activity measure (IBDDAM) and BD
current activity form (BDCAF). We tested the performances of PEDBD and ISG
criteria and the correlation between severity scores and physician global
assessment (PGA) in children with BD. METHODS: Thirty BD patients from Hacettepe
University, Ankara, Turkey; 24 from Erciyes University, Kayseri, Turkey; and 14
BD patients from Rambam Medical Centre, Haifa, Israel were included. As controls,
children with systemic lupus erythematosus, polyarteritis nodosa, and Crohn
disease from Turkey and Israel were included. The sensitivity and specificity of
the PEDBD and ISG criteria were evaluated based on the features of the patients
before or at 16 years of age. The gold standard for the diagnosis of BD was based
on expert opinion at each centre. Expert PGA (visual analogue scale between 0-10;
where 0 indicates no disease activity), IBDDAM, and BDCAF were evaluated at the
time of diagnosis and at last follow-up in all patients. RESULTS: Sixty-eight BD
(disease onset<=16 years; 44.1% male) and 90 control patients were included. The
sensitivity and specificity of PEDBD/ISG criteria were 73.5%/52.9% and
97.7%/100%, respectively. Thirty-two (47%) patients with BD failed to fulfill ISG
criteria while almost all met PEDBD criteria. The median (interquartile range;
IQR) IBDDAM and BDCAF scores at diagnosis were 6(4)/4(2); significantly decreased
to 1(2)/1(2), respectively at latest follow-up (p<0.001 for both). The median
(IQR) PGA score at diagnosis was 5(2); significantly decreased to 1(2) at latest
follow-up (p<0.001). IBDDAM positively correlated with BDCAF (r=0.637; p<0.001).
PGA positively correlated with BDCAF and IBDDAM (r=0.502; p<0.001 and
r=0.624;p<0.001, respectively). CONCLUSIONS: In our study, the PEDBD criteria
showed better sensitivity than ISG criteria which is a big advantage for
paediatric patients for early diagnosis. We also demonstrated that the severity
scores were positively correlated with each other and PGA; thus may be used in
clinical practice for paediatric BD patients.
PMID- 28406762
TI - Criteria for fibromyalgia? What is fibromyalgia? Limitations to current concepts
of fibromyalgia and fibromyalgia criteria.
PMID- 28406763
TI - Do women with fibromyalgia present higher cardiovascular disease risk profile
than healthy women? The al-Andalus project.
AB - OBJECTIVES: To analyse the cardiovascular disease risk profile of women with
fibromyalgia and compare it with control women; and to test whether physical
activity is associated with the cardiovascular disease risk profile in this
population. METHODS: This cross-sectional study comprised 436 women with
fibromyalgia (51.4+/-7.5 years old) and 217 controls (48.4+/-9.6 years old) from
Andalusia, Spain. Clinical data, waist circumference, body fat percentage,
resting heart rate, blood pressure and cardiorespiratory fitness were assessed.
Moderate-to-vigorous physical activity was objectively assessed with
accelerometry. A clustering of individual cardiovascular disease risk factors was
represented by the number of cigarettes/day, adiposity, mean arterial pressure,
resting heart rate and cardiorespiratory fitness. RESULTS: Women with
fibromyalgia presented higher waist circumference and body fat percentage,
greater number of cigarettes/day consumption and lower levels of
cardiorespiratory fitness after controlling for age, marital status, educational
level, occupational status, medication for cholesterol and monthly regular
menstruation (all, p<.05). Women with fibromyalgia showed higher clustered
cardiovascular disease risk than control women after controlling for the
potential confounders described above (p<.001). Women with fibromyalgia who did
not meet moderate-to-vigorous physical activity recommendations showed increased
clustered cardiovascular disease risk after adjusting for the potential
confounders described above (p<.001). CONCLUSIONS: Women with fibromyalgia may
present higher risk of cardiovascular disease than controls. Inadequate levels of
moderate-to-vigorous physical activity may play a significant role as an
additional predisposing factor for cardiovascular disease risk in this
population.
PMID- 28406764
TI - The efficacy of tocilizumab for the treatment of Chinese Takayasu's arteritis.
AB - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of
tocilizumab (TCZ) in Chinese Takayasu's arteritis (TAK) patients. METHODS: This
was a single-centre prospective study. Sixteen consecutive TAK patients were
included. Patients were treated with tocilizumab infusions with a dosage of 8
mg/kg. Serum inflammation markers including erythrocyte sedimentation rate (ESR)
and hypersensitivity C-reactive protein (hsCRP) were recorded at baseline and
before each TCZ infusion. Doppler ultrasonography was used to track vascular
changes every 6 months during the study. The efficacy and safety profile of
patients during the study were collected and analysed. RESULTS: Sixteen patients
with a median age of 26.5 (18-47) were recruited and analysed. One patient was
treatment naive; the others had taken a median of 3 (1-5) conventional immune
suppressants before TCZ therapy. Three patients withdrew TCZ after 1 infusion due
to unbearable neck pain. The other 13 patients were treated with TCZ for a median
of 13 (7-20) months. After TCZ treatment, the median ESR, hsCRP level, mural
thickness of common carotid artery and subclavical artery decreased from 39 (7
92) mm/h, 28.88 (7.6-155.93) mg/L, 0.24 (0.06-0.59) cm, 0.18 (0.07-0.47) cm to 6
(1-30) mm/h (p<0.001), 0.59 (0.08-19.12) mg/L (p=0.006), 0.17 (0.04-0.53) cm
(p<0.001), and 0.12 (0.07-0.18) cm (p=0.035) respectively. The
glucocorticosteroid dosage was tapered or maintained in all patients. One episode
of urinary infection was recorded and relieved after antibiotic therapy. Neither
neutropenia nor abnormal liver enzyme was observed. CONCLUSIONS: Our study
suggests that TCZ is a safe and effective agent for long-term treatment in
Chinese TAK patients.
PMID- 28406765
TI - Maintenance treatment of ANCA-associated vasculitides.
AB - ANCA-associated vasculitis(AAV) covers a group of systemic necrotising
vasculitides characterised by inflammation of small vessels, sometimes with
granuloma, and associated with autoantibodies to neutrophil cytoplasmic proteases
(proteinase-3 or myeloperoxidase). Potentially lethal if not promptly diagnosed
and treated, AAV in most patients can be induced into remission with the current
treatment modalities. However, the risk of relapse remains high, necessitating
prolonged immunosuppressive or immunomodulating maintenance therapy, whose
optimal duration remains undetermined. Herein, we review only maintenance
treatments for AAVs.
PMID- 28406766
TI - Homocysteine as a Biomarker for Thrombosis: What is the Learning Curve?
PMID- 28406767
TI - Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker
for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic
Ovarian Syndrome.
AB - OBJECTIVE: To assess the utility of HOMA-IR in assessing insulin resistance in
patients with polycystic ovary syndrome (PCOS) and compare it with fasting
insulin for assessing insulin resistance (IR). STUDY DESIGN: Observational study.
PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of
Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi,
from January 2009 to September 2012. METHODOLOGY: Medical chart review of all
women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met
the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR
using the formula (fasting glucose x fasting insulin)/405, taking normal value <2
in adults and hyperinsulinemia based on fasting insulin levels >=12 uIU/ml.
RESULTS: A total of 91 premenopausal women diagnosed with PCOS were included.
Mean age was 30 +/-5.5 years. Mean HOMA-IR of women was 3.1 +/-1.7, respectively
with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55)
women (fasting Insulin 18.5 +/-5.8 uIU/ml). Hyperandrogenism was present in 53.8%
(n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while
65.9% (n=60) had menstrual irregularities; and higher frequencies were observed
in women with IR. Eight subjects with IR and endocrine abnormalities were missed
by fasting insulin. CONCLUSION: Insulin resistance is common in PCOS and it is
likely a pathogenic factor for development of PCOS. HOMAIR model performed better
than hyperinsulinemia alone for diagnosing IR.
PMID- 28406768
TI - Ultrasonographic Findings of Liver in Chronic Liver Disease and its Complications
and Their Association with the Duration of the Disease.
AB - OBJECTIVE: To evaluate the ultrasound abdomen findings in patients having viral
chronic liver disease (CLD) and build correlation of these findings with the
duration of disease. STUDY DESIGN: Cross-sectional analytical study. PLACE AND
DURATION OF STUDY: Department of Medicine, Liaquat University Hospital, Hyderabad
and Jamshoro, Pakistan, from February to July 2016. METHODOLOGY: Known cases of
CLD were inducted. Data was collected using a standardized form which included
details of patients, duration of disease and their ultrasound abdomen findings,
like liver size, echo pattern and echogenicity, nodularity, intrahepatic vessel
(IHV) obliteration, ascites and splenomegaly. Data were analyzed using SPSS
version 16. The association of duration of the disease on ultrasound findings was
studied by means of chi-square test. RESULTS: A total of 193 subjects (92 males,
101 females; age range 14-80 years) were taken. The average measured liver span
was 13.99 +/-3.14 cm, with most coarse echo pattern. About a quarter, i.e. 26.94%
of the cases, had no complications; 17.62% only had ascites and 16.06% presented
with IHV obliteration, and ascites with splenomegaly. The duration had no
significant association with liver size, echo pattern and echogenicity, and
nodularity of the liver (p-values of 0.182, 0.331 and 0.268), respectively or
complications (p=0.164). CONCLUSION: The duration of CLD had no significant
association with the ultrasound findings of liver.
PMID- 28406769
TI - Dexamethasone Effect on the Expression of Transforming Growth Factor-beta1/Smads
Signaling Pathway in Benign Biliary Stricture Fibroblasts in Rodent.
AB - OBJECTIVE: To investigate the effects of dexamethasone on transforming growth
factor (TGF)-beta1/Smads signaling pathway in benign biliary stricture (BBS)
fibroblasts. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY:
Guizhou Medical University, Guiyang, Guizhou, China, from January to August 2016.
METHODOLOGY: Fibroblasts derived from rabbit BBS model were cultured and
identified, then treated by different concentration of dexamethasone (0.02, 0.1
and 0.5 mg/ml). Dexamethasone-treated cells and non-treated control groups were
incubated respectively for 48 hours. Cell proliferation was assessed using cell
counting kit-8. Relative mRNA expression of TGF-beta1, Smad4 and Smad7 were
assessed by quantitative RT-PCR. Protein expression of TGF-beta1 and Smad4 were
investigated by Western blotting. RESULTS: Treatment with dexamethasone
significantly inhibited the proliferation of BBS fibroblasts, significantly
attenuated both the mRNA and protein expression of TGF-beta1 and Smad4, and
significantly up-regulated the mRNA expression of Smad7 in BBS fibroblasts (all
p<0.05, 0.1-0.5 mg/ml), and exhibited in a dose-dependent manner. CONCLUSION: TGF
beta1/Smads signaling pathway may play an important role in BBS progression;
dexamethasone significantly altered the expression of TGF-beta1/Smads signaling
pathway and significantly inhibited cell proliferation in rabbit BBS fibroblasts.
Therefore, dexamethasone may be a therapeutic option for the prevention of BBS.
PMID- 28406770
TI - Frequency and Antibiogram of Isolates from Surgical Units of a Tertiary Care
Hospital in Quetta.
AB - OBJECTIVE: To determine the frequency and antibiogram of the isolates from
infected patients in surgical units of a tertiary care hospital. STUDY DESIGN:
Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Department of
Microbiology, Combined Military Hospital, Quetta, from March to October 2015.
METHODOLOGY: Clinical samples from the surgical units received in Department of
Microbiology for culture and sensitivity were analyzed by Gram stain, culture and
biochemical tests for identification of the isolates; and the antibiotic
susceptibility was determined by modified Kirby Bauer disc diffusion method. Data
was analyzed by Statistical Package for Social Sciences (SPSS) version 19.
RESULTS: The commonest isolate was Acinetobacter baumannii (22%) followed by
Escherichia coli (20%), Pseudomonas spp. (15%) and Methicillin-resistant
Staphylococcus aureus (MRSA) (11%). Acinetobacter baumannii showed highest
susceptibility to doxycycline (41%), Enterobacteriaceae to meropenem (96%),
Pseudomonas spp. to polymyxin-B (100%) and Gram positive bacteria to linezolid
(100%). Seventy-two percent of the isolates were found to be multi-drug
resistant. CONCLUSION: There was a high infection rate in surgical patients with
Acinetobacter baumannii, Eschericia coli, Pseudomonas spp. and MRSA being the
commonest isolates. Acinetobacter baumannii showed highest susceptibility to
doxycycline, Enetrobacteriaceae to meropenem, Pseudomonas spp. to polymyxin-B and
Gram positive bacteria to linezolid.
PMID- 28406771
TI - Comparison of the Long-term and Short-term Fluctuations of Frequency-Doubling
Technology Perimetry Between Peripheral and Paracentral Zones of Visual Field.
AB - OBJECTIVE: To compare the long- and short-term fluctuations of frequency doubling
technology perimetry between peripheral and paracentral zone and determine the
relationship between threshold sensitivity and long- and short-term fluctuation
within peripheral and paracentral zone of visual field. STUDY DESIGN: Descriptive
study. PLACE AND DURATION OF STUDY: Eye Department, United Nations, Pakistan
Field Hospital Level-3 Darfur, Sudan, from February to July 2015. METHODOLOGY:
Normal eyes of 30 volunteers were recruited. Frequency doubling technology
perimetry, program N-30, full threshold was employed. Each subject was tested at
weekly intervals, once in the 1st, 3rd and 4th sessions and three times in the
2nd session. Visual field was divided into paracentral, superior, and inferior
zones. Short-term and long-term fluctuation as well as threshold sensitivity were
calculated for each patient as the mean fluctuation and mean sensitivity value.
Mann-Whitney U-test was used to compare each zone in terms of their short- and
long-term fluctuations and Spearman's rho correlation test for determining the
relationship of threshold sensitivity with short- and long-term fluctuations.
RESULTS: Long-term fluctuation values differences were insignificant between
superior and paracentral zones. Short-term fluctuation values were statistically
insignificant between all three zones. Short-term fluctuation and threshold
sensitivity in each zone did not correlate. Long-term fluctuation and threshold
sensitivity had a very weak negative, statistically insignificant correlation in
superior and paracentral zones. CONCLUSION: Frequency doubling perimetry exhibits
uniform short- and long-term fluctuations in peripheral and paracentral zones of
visual field in normal subjects. Threshold sensitivity and long- and short-term
fluctuations are independent of each other in peripheral and paracentral zones of
visual field.
PMID- 28406772
TI - Crigler Massage for Congenital Blockade of Nasolacrimal Duct.
AB - OBJECTIVE: To determine the success rate of non-surgical management of congenital
nasolacrimal duct obstruction (CNLDO) with Crigler massage in infants below the
age of one year. STUDY DESIGN: A cross-sectional observational study. PLACE AND
DURATION OF STUDY: Department of Ophthalmology at HBS General Hospital, Hazrat
Bari Sarkar Medical and Dental College, Islamabad from November 2015 to May 2016.
METHODOLOGY: One hundred children with watering of eyes, due to congenital
blockage of the distal part of the nasolacrimal duct (at the valve of Hasner),
unilateral or bilateral were included in the study. Initially, Crigler massage
was advised to all the parents for a period of 1-3 months with practical
demonstration and the results were documented every fortnight. RESULTS: There
were 52 infants up to the age of 6 months and 48 infants between 6-12 months, 53%
were boys and 47% were girls. Among them, 67% had unilateral complain while 33%
were bilaterally affected. At the end of 1-3 months, 90% of the children achieved
patency and only 10% of the cases were subjected to Bowman's probing under short
anesthesia. CONCLUSION: CNLDO mostly resolved through conservative approach by
Crigler massage as an initial management, if done consistently. Probing and other
surgical procedures should not be considered before the age of 12 months.
PMID- 28406773
TI - Cluster of Differentiation 5 (CD5) Levels in the Plasma of Children with Autism
Spectrum Disorder (ASD).
AB - OBJECTIVE: To investigate the cluster of differentiation 5 (CD5) plasma levels
and their association with childhood autism rating scale (CARS) in subjects with
autism spectrum disorder (ASD) compared to age and gender matched healthy
controls, and to explore the link between CD5, severity, and autoimmunity in
autism. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Autism
Research and Treatment Center, Al-Amodi Autism Research Chair, Department of
Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud
University, Riyadh, Saudi Arabia, from October 2014 to May 2015. METHODOLOGY: CD5
levels were determined in the plasma of thirty-one (31) patients using enzyme
linked immunosorbent assay (ELISA), categorized as mild-moderate and severe as
indicated by their Childhood Autism Rating Scale (CARS) score and compared to
thirty-three (33) age and gender-matched control samples. RESULTS: The
preliminary data indicated that children with severe autism (n=12), exhibited
significantly (p=0.02) higher plasma level of CD5 [0.55 (0.14-12) pg/ml {median
(interquartile range=IQR)}] than those of normal controls [n=33, 0.29 (0.08-0.79)
pg/ml {median (IQR)}] and children with mild to moderate autism [n=19, 0.26 (0.13
1.42) pg/ml, {median (IQR)}, p=0.08]. However, there was no significant
difference between the CD5 levels of children with mild to moderate autism and
normal controls (p = 0.62). Diagnoses of autistic children based on the CARS
score >30. Disease severity and the CARS score, which represent stereotyped
patterns of behavior in children with autism, were positively correlated (r =
0.43, p = 0.02). CONCLUSION: The high CD5 plasma levels in patients with severe
ASD, probably indicated that CD5 might be implicated in the physiology of autism.
However, this finding should be treated with caution until further investigations
are performed with larger populations to determine whether the increase in plasma
CD5 levels is a mere consequence of autism or it plays a pathogenic role in the
disease.
PMID- 28406774
TI - Effect of Ligation of the Thoracic Duct During Oesophagectomy on the Absorption
of D-xylose.
AB - OBJECTIVE: To assess if prophylactic thoracic duct ligation during oesophagectomy
influences the absorptive function of oesophageal cancer patients. STUDY DESIGN:
Randomized controlled trial. PLACE AND DURATION OF STUDY: Department of Thoracic
Surgery, Tai'an City Central Hospital, Tai'an, from August 2014 to December 2015.
METHODOLOGY: Based on the management of the thoracic duct during oesophagectomy,
60 patients were randomized into two groups. D-xylose absorption test was used to
evaluate the absorptive function. The two-independent-samples t-test was employed
for statistical analysis with statistical significance at p < 0.05. RESULTS: The
serum D-xylose concentration of ligation-group was significantly lower than that
of no-ligation group on the first day after operation, (t=2.82, p=0.0066).
However, there was no significant differences between them even before operation
(t=1.34, p=0.1849). CONCLUSION: Ligation of the thoracic duct during
oesophagectomy immediately affected the absorption of D-xylose, which may lead to
malabsorption in the long run.
PMID- 28406775
TI - Motivating and Demotivating Factors for Community Health Workers Engaged in
Maternal, Newborn and Child Health Programs in Low and Middle-Income Countries: A
Systematic Review.
AB - This systematic review aimed to synthesize primary research on motivating factors
of community health workers (CHWs) for maternal, neonatal, and child health
(MNCH) in low and middle-income countries (LMICs). Peer-reviewed literatures were
systematically searched in five databases. Identified studies were then screened
and selected for inclusion. The eligibility criteria were reported primary
qualitative, quantitative, or mixed methods research, with participants being
CHWs in LMICs who address MNCH, which investigated motivation or related concepts
of retention, attrition, and performance. A thematic synthesis process was used
to analyze findings of motivating factors, reported by included studies.
Seventeen qualitative, quantitative, or mixed methods studies met inclusion
criteria. Two overarching themes were developed: Levels of motivation (i.e.
individual, community, and health system) and stages of motivation (i.e.
recruitment, retention, and attrition). Nine sub-themes were further developed at
the intersection of each level and stage of motivation. Each subtheme comprises
the motivating factors that are influential to community health workers at each
stage and level. These themes and sub-themes are presented in a Community Health
Worker Motivation Model. The motivation model can be used to identify what
motivating factors are relevant to community health workers motivation and the
stakeholders necessary to address each motivating factor. Recruitment of
community health workers for maternal, neonatal, and child health relies largely
on individual level of motivation. At retention, individual level motivating
factors remain influential; and community and health system begin to influence
motivation positively. But, overall health systems in low and middleincome
countries are demotivating the health workers rather than motivating them.
PMID- 28406776
TI - Gastric Intestinal Metaplasia: An Intermediate Precancerous Lesion in the Cascade
of Gastric Carcinogenesis.
AB - Gastric intestinal metaplasia, an intermediate lesion in the development of
intestinal-type gastric cancer, is observed in the milieu of long standing non
atrophic gastritis and atrophic gastritis. Most patients with intestinal
metaplasia remain asymptomatic unless cobalamin deficiency occurs secondary to
loss of glands (that produce intrinsic factor and acid). Genetic events that
predispose to development of gastric intestinal metaplasia remains an enigma.
Mechanisms leading to the progression of atrophy to metaplasia still needs to be
comprehensively explored. Many studies in the literature describe a positive
effect of typing intestinal metaplasia and concluded that intestinal metaplasia
type III carries the highest risk for developing gastric cancer while others
refute it. It is well established that Helicobacter pylori infection is the most
important factor for the development of chronic gastritis, gastric intestinal
metaplasia as well as gastric cancer. Countries with a higher prevalence of
Helicobacter pylori infection and gastric cancer also have a high tendency of
being prevalent for intestinal metaplasia. However, it remains elusive whether
eradication of Helicobacter pylori infection tends to regress gastric intestinal
metaplasia or reduce the subsequent risk of cancer development. Putting together,
more prospective cohort studies should be designed to identify factors
(antioxidants; anti-inflammatory drugs; food therapy) that may contribute in the
regression of intestinal metaplasia, when used simultaneously with eradication
therapy. Furthermore, molecular markers for evaluation of intestinal metaplasia,
and the potential point-of-no-return should be further investigated. Consensus is
also required to advocate a timeframe for surveillance of patients with gastric
intestinal metaplasia.
PMID- 28406777
TI - Surgical Management for Symptomatic Giant Liver Hemangiomas: A Meta-Analysis.
AB - OBJECTIVE: To conduct a meta-analysis of reported evidence on surgical management
for symptomatic giant liver hemangiomas. METHODOLOGY: A systematic literature
search was conducted to identify studies on adult patient surgeries for
symptomatic giant liver hemangiomas from January 2009 to July 2015. The primary
outcome measures included postoperative symptom resolution, mortality,
complications, and blood transfusions. Quality of life after surgery was taken as
a secondary outcome. Meta-analysis was performed using a random-effect model with
comprehensive meta-analysis software. RESULTS: Fourteen studies with 1,557
patients were included. There were only two mortalities. Overall event rate for
minor and major complications was low as 0.15 and 0.14, respectively, with a high
symptom resolution rate of 0.69 (95%, CI 0.64-0.73). Pooled analysis for blood
transfusion stayed insignificant due to high calculated heterogeneity across
studies. Quality of life results after surgery are reported good by three
studies, in most of their patients. The adverse outcome rate between enucleation
and resection was comparable. CONCLUSION: Liver hemangioma surgery is a safe
treatment option with negligible mortality and low morbidity. It is effective in
terms of symptom control and overall quality of life.
PMID- 28406778
TI - Appendicular Diverticulosis with Appendicitis.
AB - Appendicular diverticulosis is one of the very rare diseases which is also
difficult to diagnose, especially clinically, due to its silent course and non
specific symptoms. It comes under the notation usually due to its complications
like diverticulitis or perforation, but sometimes it also presents with acute
appendicitis. This report describes a 44-year male patient who presented with the
complain of right iliac fossa pain and was clinically diagnosed as acute
appendicitis; but intraoperatively, it was found that the appendix also had
diverticulosis along with appendicitis.
PMID- 28406779
TI - Classic Raymond Syndrome.
AB - Classic Raymond syndrome presents with abducens nerve palsy on the ipsilateral
side with contralateral hemiparesis and facial nerve paralysis. A 60-year
gentleman presented with deviation of left angle of mouth and right sided
weakness. Examination showed that he had left sided abducens nerve palsy, with
contralateral central facial paralysis and paresis. MRI of brain confirmed left
pontine infarct. These findings were consistent with classic Raymond syndrome.
Till now, only a few cases have been reported worldwide, this being the first
case reported in South Asia. This case confirms that classic Raymond syndrome is
different from the common type of Raymond syndrome in terms of sparing of
coritcofacial fibers in the latter type.
PMID- 28406780
TI - Dysphagia: An Unusual Presentation of Metastatic Uterine Cervical Carcinoma.
AB - Worldwide, cervical cancer is the third most common cancer among women and the
fourth leading cause of death from cancer. The most common sites of metastasis
are the pelvic lymph nodes, vagina, and the pelvic sidewalls. Distant metastases
are uncommon but can involve the bone, lung, and liver. Characteristics
associated with increased rate of distant metastasis include bulky tumor,
endometrial extension, lymph node involvement, and advanced disease. We report
the case of a woman with stage II cervical carcinoma, who presented with
dysphagia due to cervical cancer metastases to the mediastinum.
PMID- 28406781
TI - Bladder Leiomyoma.
AB - Leiomyoma of the bladder is a very rare disorder that accounts for 0.43% of all
bladder neoplasms. Although the pathophysiology of the bladder leiomyoma is
unknown, there are some theories in it. The patients can be asymptomatic; and
clinical symptoms, when present, are associated with the tumor size and location.
Imaging techniques such as ultrasonography, intravenous urography, computed
tomography, and magnetic resonance imaging are helpful but definitive diagnosis
is made by histopathological examination. Surgical resection of tumor with
transurethral, open, laparoscopic and robotic approaches is the main treatment.
We present a case of leiomyoma of the bladder in an adult male patient.
PMID- 28406782
TI - Physical Manipulation of Larynx as a Technique for Insertion of Nasogastric Tube.
PMID- 28406783
TI - Diastolic Dysfunction in Coronary Artery Disease.
PMID- 28406784
TI - The Cost of Curriculum Overload.
PMID- 28406785
TI - Primary Axillary Hydatid Cyst: An Extremely Rare Manifestation of Hydatid
Disease.
PMID- 28406786
TI - Communication with Physicians about Health Care Costs: Survey of an Insured
Population.
AB - CONTEXT: Health care costs have increasingly shifted to patients, and financial
distress caused by medical care has increased. Patients may wish to discuss costs
with their clinicians. OBJECTIVE: Describe patient preferences for communication
about cost in the clinical setting. DESIGN: Cross-sectional, self-administered
survey of a stratified random sample of the population insured in an integrated
health care system in Washington State. Our sampling frame was the entire
membership aged 21 years or older. Sampling was stratified by sex and group
practice enrollment. MAIN OUTCOME MEASURES: Preference for discussing health care
costs with one's physician. We conducted regression analyses to determine
predictors of communication preference; potential predictors included demographic
characteristics, financial burden, delay in seeking care because of cost, and
socioeconomic variables. Survey responses were weighted to adjust for nonresponse
and sampling. RESULTS: Of 7200 invitations sent, 2200 survey responses were
returned. Ninety-two percent wished to know their out-of-pocket costs before
beginning treatment. Most respondents preferred their physician talk with them
about out-of-pocket costs (81.4%) and expressed comfort with discussing costs
with their physician (75.6%). Overall, 43.7% reported any delay in seeking care
in the previous 12 months. One in 5 respondents (21.6%) reported family medical
debt. Delay in seeking care was positively and independently associated with
preferring to discuss costs with one's physician; current medical financial
burden was not. CONCLUSION: Patient preferences for communication about costs
with physicians are high, and medical debt and delay in care-seeking are
prevalent. Delay in care-seeking independently predicts cost communication
preferences.
PMID- 28406787
TI - Factors Influencing Helmet Use, Head Injury, and Hospitalization Among Children
Involved in Skateboarding and Snowboarding Accidents.
AB - CONTEXT: Up to 75% of skateboarders and snowboarders admitted to the hospital
sustain head injuries. It is unclear why not all children and teenagers wear
helmets while snowboarding and skateboarding given the protection they afford.
OBJECTIVES: To report on the prevalence of, and factors associated with,
skateboarding and snowboarding in injured children and to explore factors that
influence helmet use, head injury, and hospitalization in this sample. DESIGN: A
cross-sectional study of skateboard- and snowboard-associated injuries from 2003
to 2012 among individuals younger than age 18 years using National Electronic
Injury Surveillance System (NEISS) data from approximately 100 hospitals. MAIN
OUTCOME MEASURES: Helmet use, head injury, and hospitalization. RESULTS: Of 1742
patients in the study, 852 (48.9%) and 890 (51.1%) were skateboarders and
snowboarders, respectively. Overall, 907 (52.1%) did not use helmets, and 704
(40.4%) sustained head injuries. Multiple logistic regression analysis showed
that age, race/ethnicity, location of boarding, and engaging in skateboarding
influenced helmet use. Sex, race/ethnicity, helmet use, and skateboarding
predicted head injury. Age, sex, skateboarding, and head injury predicted
hospital admission. CONCLUSION: Statistically significant differences exist in
helmet use, head injury, and hospitalization rates between skateboarders and
snowboarders. Our findings suggest that injury prevention and outreach programs
are needed to increase helmet use and reduce the risk of head injury and
hospitalization in skateboarders and other at-risk groups. Further studies are
needed to clarify the association between race/ethnicity and helmet use among
skateboarders and snowboarders.
PMID- 28406788
TI - Improving Patient-Centered Care by Assessing Patient Preferences for Multiple
Sclerosis Disease-Modifying Agents: A Stated-Choice Experiment.
AB - CONTEXT: Long-term adherence to pharmaceutical treatment for multiple sclerosis
(MS) is poor. A focus on patient preferences when determining the patient's
therapeutic plan may improve this experience. OBJECTIVE: To identify factors
important to patients with MS when evaluating their options for pharmaceutical
agents that deliver disease-modifying therapy. DESIGN: Stated-choice experiment
to a sample of patients with MS from privately and publicly insured enrollees in
a regional health plan. The experiment presented each respondent with a set of 8
drug choices for MS, asking them to select their preferred disease-modifying
agent (DMA). Each respondent was randomized to 1 of 6 possible sets of 8 drug
choices, for a total of 48 drug pairings in the experiment. Each choice included
2 hypothetical DMAs and a "no drug" option. Drug attributes included dosage type
and modality, efficacy, relapse risk, and drug side effects. RESULTS: The "no
drug" alternative was a stronger substitute than the alternative drug when the
focal drug characteristics changed, and the most important drivers of choice were
type of side effects and risk of severe relapse. DISCUSSION: The heterogeneity of
our sample and the inclusion of a "no drug" alternative in the DMA choice
scenarios make this study an important contribution to this body of literature.
The importance of the "no drug" alternative in our results is consistent with
poor long-term adherence to DMAs. CONCLUSION: Patient-centered MS therapy using
DMAs should include discussion of side effects and relapse risk.
PMID- 28406789
TI - Risk of Venous Thromboembolism after a Single Normal Proximal Lower Extremity
Venous Ultrasound.
AB - CONTEXT: The optimal lower extremity venous ultrasound (US) protocol to diagnose
deep venous thrombosis of the popliteal and more proximal veins is unclear.
OBJECTIVE: To determine the three-month rate of symptomatic venous
thromboembolism (VTE) and clinical outcomes of inpatients and ambulatory patients
with normal findings on single venous ultrasound of the popliteal and more
proximal veins (single proximal US). DESIGN: Single proximal US results and
clinical data of all inpatient and ambulatory patients with suspected acute deep
venous thrombosis were retrospectively reviewed during a 12-month period between
January and December 2014. Three-month follow-up data were reviewed for all these
patients, who received all their care from a single geographically isolated
health maintenance organization. MAIN OUTCOME MEASURES: Three-month rate of
symptomatic VTE and clinical outcomes after an initially normal single proximal
US result. RESULTS: Of 1295 patients, 111 (8.6%) were found to have acute deep
venous thrombosis on the initial proximal US. Of the remaining 1184 patients with
initially normal results on proximal US who were sampled at 3-month follow-up,
1075 patients (90.8%) had no venous thromboembolic event. Among the others, 11
(0.9%) had a subsequent imaging-confirmed venous thromboembolic event, 53 (4.5%)
died (none owing to venous thromboembolism), and 45 (3.8%) did not complete
follow-up. CONCLUSION: Symptomatic VTE after an initially normal single proximal
US result occurred in less than 1% of this cohort. Therefore, serial proximal US
is unnecessary for most of our patients, and its elimination will save time and
out-of-pocket expenses.
PMID- 28406790
TI - Image Diagnosis: Numb Chin Syndrome.
PMID- 28406791
TI - Health Care Systems Support to Enhance Patient-Centered Care: Lessons from a
Primary Care-Based Chronic Pain Management Initiative.
AB - BACKGROUND: Supporting day-to-day self-care activities has emerged as a best
practice when caring for patients with chronic pain, yet providing this support
may introduce challenges for both patients and primary care physicians. It is
essential to develop tools that help patients identify the issues and outcomes
that are most important to them and to communicate this information to primary
care physicians at the point of care. OBJECTIVE: We describe our process to
engage patients, primary care physicians, and other stakeholders in the context
of a pilot randomized controlled trial of a patient-centered assessment process
implemented in an everyday practice setting. We identify lessons on how to engage
stakeholders and improve patient-centered care for those with chronic conditions
within the primary care setting. METHODS: A qualitative analysis of project
minutes, interviews, and focus groups was conducted to evaluate stakeholder
experiences. Stakeholders included patients, caregivers, clinicians, medical
office support staff, health plan administrators, an information technology
consultant, and a patient advocate. RESULTS: Our stakeholders included many
patients with no prior experience with research. This approach enriched the
applicability of feedback but necessitated extra time for stakeholder training
and meeting preparation. Types of stakeholders varied over the course of the
project, and more involvement of medical assistants and Information Technology
staff was required than originally anticipated. CONCLUSION: Meaningful engagement
of patient and physician stakeholders must be solicited in a well-coordinated
manner with broad health care system supports in place to ensure full execution
of patient-centered processes.
PMID- 28406792
TI - Image Diagnosis: Unusual Cause of Gastrointestinal Bleeding in a Young Man:
Isolated Gastric Angiodysplasias.
PMID- 28406793
TI - Population-Level Incidence and Predictors of Surgically Induced Diabetes and
Exocrine Insufficiency after Partial Pancreatic Resection.
AB - CONTEXT: Endocrine and exocrine insufficiency after partial pancreatectomy affect
quality of life, cardiovascular health, and nutritional status. However, their
incidence and predictors are unknown. OBJECTIVE: To identify the incidence and
predictors of new-onset diabetes and exocrine insufficiency after partial
pancreatectomy. DESIGN: We retrospectively reviewed 1165 cases of partial
pancreatectomy, performed from 1998 to 2010, from a large population-based
database. MAIN OUTCOME MEASURES: Incidence of new onset diabetes and exocrine
insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8%
had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months,
diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235
(34.7%) patients. Independent predictors of new-onset diabetes were higher
Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02;
HR = 1.95 for CCI >= 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There
was no difference in diabetes after Whipple procedure vs distal pancreatic
resections, or malignant vs benign pathologic findings. Independent predictors of
exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR
= 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI >= 2, p < 0.01). Distal
resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p
< 0.01; HR = 0.54, p < 0.01, respectively). CONCLUSION: In a large population
based database, the rates of postpancreatectomy endocrine and exocrine
insufficiency were 40% and 35%, respectively. These data are critical for
informing patients' and physicians' expectations.
PMID- 28406794
TI - Experiences in an Italian Rehabilitation Hospital-Two Stories.
PMID- 28406795
TI - Prototype pre-clinical PET scanner with depth-of-interaction measurements using
single-layer crystal array and single-ended readout.
AB - In this study, we developed a proof-of-concept prototype PET system using a pair
of depth-of-interaction (DOI) PET detectors based on the proposed DOI-encoding
method and digital silicon photomultiplier (dSiPM). Our novel cost-effective DOI
measurement method is based on a triangular-shaped reflector that requires only a
single-layer pixelated crystal and single-ended signal readout. The DOI detector
consisted of an 18 * 18 array of unpolished LYSO crystal (1.47 * 1.47 * 15
mm3) wrapped with triangular-shaped reflectors. The DOI information was encoded
by depth-dependent light distribution tailored by the reflector geometry and DOI
correction was performed using four-step depth calibration data and maximum
likelihood (ML) estimation. The detector pair and the object were placed on two
motorized rotation stages to demonstrate 12-block ring PET geometry with 11.15 cm
diameter. Spatial resolution was measured and phantom and animal imaging studies
were performed to investigate imaging performance. All images were reconstructed
with and without the DOI correction to examine the impact of our DOI measurement.
The pair of dSiPM-based DOI PET detectors showed good physical performances
respectively: 2.82 and 3.09 peak-to-valley ratios, 14.30% and 18.95% energy
resolution, and 4.28 and 4.24 mm DOI resolution averaged over all crystals and
all depths. A sub-millimeter spatial resolution was achieved at the center of the
field of view (FOV). After applying ML-based DOI correction, maximum 36.92%
improvement was achieved in the radial spatial resolution and a uniform
resolution was observed within 5 cm of transverse PET FOV. We successfully
acquired phantom and animal images with improved spatial resolution and contrast
by using the DOI measurement. The proposed DOI-encoding method was successfully
demonstrated in the system level and exhibited good performance, showing its
feasibility for animal PET applications with high spatial resolution and
sensitivity.
PMID- 28406796
TI - Experimental dosimetric comparison of 1H, 4He, 12C and 16O scanned ion beams.
AB - At the Heidelberg Ion Beam Therapy Center, scanned helium and oxygen ion beams
are available in addition to the clinically used protons and carbon ions for
physical and biological experiments. In this work, a study of the basic
dosimetric features of the different ions is performed in the entire therapeutic
energy range. Depth dose distributions are investigated for pencil-like beam
irradiation, with and without a modulating ripple filter, focusing on the
extraction of key Bragg curve parameters, such as the range, the peak-width and
the distal 80%-20% fall-off. Pencil-beam lateral profiles are measured at
different depths in water, and parameterized with multiple Gaussian functions. A
more complex situation of an extended treatment field is analyzed through a
physically optimized spread-out Bragg peak, delivered with beam scanning. The
experimental results of this physical beam characterization indicate that helium
ions could afford a more conformal treatment and in turn, increased tumor
control. This is mainly due to a smaller lateral scattering than with protons,
leading to better lateral and distal fall-off, as well as a lower fragmentation
tail compared to carbon and oxygen ions. Moreover, the dosimetric dataset can be
used directly for comparison with results from analytical dose engines or Monte
Carlo codes. Specifically, it was used at the Heidelberg Ion Beam Therapy Center
to generate a new input database for a research analytical treatment planning
system, as well as for validation of a general purpose Monte Carlo program, in
order to lay the groundwork for biological experiments and further patient
planning studies.
PMID- 28406798
TI - A 75-Year-Old Man With Progressive Generalized Erythroderma and History of
Anaplastic Large Cell Lymphoma: Challenge.
PMID- 28406799
TI - Granulomatous Reaction After Complete Resolution of Primary Varicella.
PMID- 28406800
TI - Simple limbal epithelial transplantation.
AB - PURPOSE OF REVIEW: Simple limbal epithelial transplant (SLET) is a technique for
addressing limbal stem cell deficiency. Limbal tissue from a donor eye, typically
the patient's fellow healthy eye, is transplanted onto an amniotic membrane
attached to the surface of the diseased eye. SLET was developed to address
limitations of other techniques, specifically the technical difficulty of ex-vivo
expansion of cells required in some techniques and the larger amount of valuable
limbal tissue harvested in techniques not relying on ex-vivo expansion. We
described how the provision of this procedure adds to the armamentarium of
techniques available to treat some of the many thousands of uniocular corneal
blind around the world. RECENT FINDINGS: A total of 125 patients from a recent
series from our centre and 68 from a multicentre study provide evidence for
efficacy mainly in cases of unilateral corneal burn. Results were comparable to
other stem cell techniques described in other papers. Numerous small case reports
describe the use of SLET in other contexts including ocular surface squamous
neoplasia and pterygium excision. SUMMARY: SLET offers a cheaper and perhaps
safer alternative to other techniques. Further evaluation of clinical success
against its most similar analogues of conjunctival limbal autograft and
cultivated limbal autograft is required.
PMID- 28406801
TI - Ultrasound-Guided S1 Transforaminal Epidural Injection Using the In-Plane
Approach and Color Doppler Imaging.
AB - Recently, several studies have investigated the effectiveness of the ultrasound
guided lumbosacral transforaminal epidural injection. However, the ultrasound
guided S1 transforaminal epidural injection using an out-of-plane approach, which
was previously reported, may cause an intestinal injury or intravascular
injection because the needle tip tends to be invisible in the out-of-plane
approach. In this study, therefore, we report a new method of ultrasound-guided
S1 transforaminal epidural injection using the in-plane approach and color
Doppler. In addition, we also report the usefulness of color Doppler imaging for
finding the S1 foramen and confirming the accuracy of the injection.
PMID- 28406802
TI - Distinct subtype distribution and somatic mutation spectrum of lymphomas in East
Asia.
AB - PURPOSE OF REVIEW: Here, we give an updated overview of the subtype distribution
of lymphomas in East Asia and also present the genome sequencing data on two
major subtypes of these tumors. RECENT FINDINGS: The distribution of lymphoma
types/subtypes among East Asian countries is very similar, with a lower
proportion of B-cell malignancies and a higher proportion of T/natural killer
(NK)-cell lymphomas as compared to Western populations. Extranodal NK/T-cell
lymphoma is more frequently observed in East Asia, whereas follicular lymphoma
and chronic lymphocytic leukemia, are proportionally lower. The incidence rate of
lymphoma subtypes in Asians living in the US was generally intermediate to the
general rate in US and Asia, suggesting that both genetic and environmental
factors may underlie the geographical variations observed.Key cancer driver
mutations have been identified in Asian patients with diffuse large B-cell
lymphoma or extranodal NK/T-cell lymphoma through genome sequencing. A distinct
somatic mutation profile has also been observed in Chinese diffuse large B-cell
lymphoma patients. SUMMARY: The incidence and distribution of lymphoma subtypes
differed significantly between patients from East Asia and Western countries,
suggesting subtype-specific etiologic mechanisms. Further studies on the
mechanism underlying these geographical variations may give new insights into our
understanding of lymphomagenesis.
PMID- 28406803
TI - Investigating Clinical Benefits of a Novel Sleep-Focused Mind-Body Program on
Gulf War Illness Symptoms: A Randomized Controlled Trial.
AB - OBJECTIVE: Mind-Body Bridging (MBB) has been shown to be effective for improving
disturbed sleep. In this prospective randomized controlled trial, we evaluated
the efficacy of sleep-focused MBB compared with sleep education control (SED) for
improving sleep in previously deployed Gulf War veterans. METHODS: US military
service members with sleep and physical health complaints who were deployed in
1990-1991 were randomized to receive three weekly sessions of either MBB (n = 33)
or SED (n = 27) between 2012 and 2015. The primary outcome of Medical Outcomes
Study Sleep Scale was completed at baseline, weekly during treatment,
postintervention, and 3-month follow-up. Secondary outcome measures for
posttraumatic stress disorder, depression, fatigue, quality of life, symptom
severity, and mindfulness were completed at baseline, postintervention and 3
month follow-up. Salivary samples were collected at five time points per day at
each visit for cortisol and alpha-amylase assessment. Clinician-administered
assessments of sleep and co-occurring conditions were conducted at baseline and
postintervention. RESULTS: MBB was significantly more efficacious than SED in
reducing disturbed sleep at follow-up (F(1,180.54) = 4.04, p = .046). In
addition, self-reported posttraumatic stress disorder (F(1,56.42) = 4.50, p =
.038) for the treatment effect, depression (F(1,93.70) = 4.44, p = .038), and
fatigue symptoms (F(1,68.58) = 3.90, p = .050) at follow-up improved in MBB
compared with those in SED. Consistently higher percentages of veterans in MBB
reported improvements of sleep, pain, and composite sleep/general co-occurring
symptoms at the postclinical evaluation, as compared with veterans in SED.
Finally, the mean waking level of salivary alpha-amylase in the MBB declined to a
greater extent than that in the SED, at follow-up (F(1,88.99) = 3.78, p = .055),
whereas no effects were found on cortisol. CONCLUSIONS: Sleep-focused MBB can
improve sleep and possibly also co-occurring symptoms in Gulf War veterans.
CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01543997.
PMID- 28406805
TI - Nothing to Spit At.
PMID- 28406804
TI - Subjective General Health and the Social Regulation of Hypothalamic Activity.
AB - OBJECTIVE: Social support is associated with better health. This association may
be partly mediated through the social regulation of adrenomedullary activity
related to poor cardiovascular health and glucocorticoid activity known to
inhibit immune functioning. These physiological cascades originate in the
hypothalamic areas that are involved in the neural response to threat. The aim of
the study investigated whether the down regulation, by social support, of
hypothalamic responses to threat is associated with better subjective health.
METHODS: A diverse community sample of seventy-five individuals, aged 23 to 26
years, were recruited from an ongoing longitudinal study. Participants completed
the Short Form Health Survey, a well-validated self-report measure used to assess
subjective general health. They were scanned, using functional magnetic resonance
imaging, during a threat of shock paradigm involving various levels of social
support, which was manipulated using handholding from a close relational partner,
a stranger, and an alone condition. We focused on a hypothalamic region of
interest derived from an independent sample to examine the association between
hypothalamic activity and subjective general health. RESULTS: Results revealed a
significant interaction between handholding condition and self-reported general
health (F(2,72) = 3.53, p = .032, partial eta = 0.05). Down regulation of the
hypothalamic region of interest during partner handholding corresponded with
higher self-ratings of general health (beta = -0.31, p = .007). CONCLUSIONS:
Higher self-ratings of general health correspond with decreased hypothalamic
activity during a task that blends threat with supportive handholding. These
results suggest that associations between social support and health are partly
mediated through the social regulation of hypothalamic sensitivity to threat.
PMID- 28406806
TI - Improved HIV and TB Knowledge and Competence Among Mid-level Providers in a
Cluster-Randomized Trial of One-on-One Mentorship for Task Shifting.
AB - INTRODUCTION: Health worker shortages pose a challenge to the scale up of HIV
care and treatment in Uganda. Training mid-level providers (MLPs) in the
provision of HIV and tuberculosis (TB) treatment can expand existing health
workforce capacity and access to HIV services. METHODS: We conducted a cluster
randomized trial of on-site clinical mentorship for HIV and TB care at 10 health
facilities in rural Uganda. Twenty MLPs at 5 randomly assigned to an intervention
facilities received 8 hours a week of one-on-one mentorship, every 6 weeks over a
9-month period; and another 20 at 5 control facilities received no clinical
mentorship. Enrolled MLPs' clinical knowledge and competence in management of HIV
and TB was assessed using case scenarios and clinical observation at baseline and
immediately after the 9-month intervention. The performance of the study health
facilities on 8 TB and HIV care indicators was tracked over the 9-month period
using facility patient records. RESULTS: Thirty-nine out 40 enrolled MLPs had
case scenario and clinical observation scores for both the baseline and end of
intervention assessments. Mentorship was associated with a mean score increase of
16.7% (95% confidence interval: 9.8 to 23.6, P < 0.001) for the case scenario
assessments and 25.9% (95% confidence interval: 14.4 to 37.5, P < 0.001) for the
clinical observations. On-site clinical mentorship was significantly associated
with an overall improvement for 5 of the 8 health facility TB and HIV indicators
tracked. CONCLUSIONS: One-on-one on-site mentorship improves individual knowledge
and competence, has a downstream effect on facility performance, and is a simple
approach to training MLPs for task shifting.
PMID- 28406808
TI - An Evaluation of the Work and Life Conditions and the Quality of Life in 60 to 65
Year-Old White-Collar Employees, Manual Workers, and Unemployed Controls.
AB - OBJECTIVES: Assessment of the work and life conditions of 60 to 65-year-old
seniors with regard to type of work and quality of life (QoL). METHODS: The
European Foundation for Improvement of Living and Working Conditions
Questionnaire and the EuroQol 5D were used to evaluate work and life conditions
and QoL in the three age- and sex-matched 60 to 65-year-old groups (white-collar,
manual workers, and unemployed subjects, 100 each group, 50% of women). RESULTS:
Manual workers and unemployed subjects had lower QoL score (0 to 100 point scale)
than white-collar workers (accordingly 72.2; 71.2; 76.2; P < 0.05). In working
subjects (n = 200), QoL was inversely associated with reported health problems (P
< 0.01) and directly related to quality of work (P < 0.001). In the group of
manual workers (n = 100), QoL indices were influenced by health factors and
quality of work, while in the intellectual group (n = 100) mainly by health
factors. CONCLUSIONS: Quality of work and health assessment are the main domains
that influence older workers' QoL and may contribute to the shortening of the
work period and accelerated transfer to retirement. Quality of work assessment
seems especially important in older manual workers.
PMID- 28406807
TI - Community-Level HIV Stigma as a Driver for HIV Transmission Risk Behaviors and
Sexually Transmitted Diseases in Sierra Leone: A Population-Based Study.
AB - INTRODUCTION: Although HIV stigma has been identified as an important risk factor
for HIV transmission risk behaviors, little is known about the contribution of
community-level HIV stigma to HIV transmission risk behaviors and self-reported
sexually transmitted diseases (STDs) or how gender may modify associations.
METHODS: We pooled data from the 2008 and 2013 Sierra Leone Demographic and
Health Surveys. For HIV stigma, we examined HIV stigmatizing attitudes and HIV
disclosure concerns at both individual and community levels. Outcomes of HIV
transmission risk behaviors were recent condom usage, consistent condom usage,
and self-reported STDs. We assessed associations with multivariable logistic
regressions. We also analyzed gender as an effect modifier of these associations.
RESULTS: Of 34,574 respondents, 24,030 (69.5%) who had heard of HIV were included
in this analysis. Community-level HIV stigmatizing attitudes and disclosure
concerns were associated with higher odds of self-reported STDs (adjusted odds
ratio = 2.07; 95% confidence interval: 1.55 to 2.77; adjusted odds ratio = 2.95;
95% confidence interval: 1.51 to 5.58). Compared with men, community-level HIV
stigmatizing attitudes among women were a stronger driver of self-reported STDs
(interaction P = 0.07). Gender modified the association between community-level
HIV disclosure concerns and both recent and consistent condom usage (interaction
P = 0.03 and P = 0.002, respectively). Community-level HIV disclosure concerns
among women were observed to be a driver of risky sex and self-reported STDs.
CONCLUSIONS: This study shows that community-level HIV stigma may be a driver for
risky sex and self-reported STDs, particularly among women. Our findings suggest
that community-held stigmatizing beliefs and HIV disclosure concerns among women
might be important targets for HIV stigma reduction interventions.
PMID- 28406809
TI - Hysteroscopy for Abnormal Uterine Bleeding and Fibroids.
AB - Operative hysteroscopy is a safe and effective minimally invasive treatment
option for submucosal and intramural leiomyomas. We discuss preoperative
evaluation, fluid management, postoperative complications, preventative measures,
and hysteroscopic outcomes. Technical instructions and tips for successful
hysteroscopy, as well as the various equipment options most commonly utilized in
the United States, are also reviewed.
PMID- 28406812
TI - Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A
Two-Center Study.
AB - OBJECTIVE: The prognostic role of electroencephalography during and after
targeted temperature management in postcardiac arrest patients, relatively to
other predictors, is incompletely known. We assessed performances of
electroencephalography during and after targeted temperature management toward
good and poor outcomes, along with other recognized predictors. DESIGN: Cohort
study (April 2009 to March 2016). SETTING: Two academic hospitals (Centre
Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester,
MN). PATIENTS: Consecutive comatose adults admitted after cardiac arrest,
identified through prospective registries. INTERVENTIONS: All patients were
managed with targeted temperature management, receiving prespecified standardized
clinical, neurophysiologic (particularly, electroencephalography during and after
targeted temperature management), and biochemical evaluations. MEASUREMENTS AND
MAIN RESULTS: We assessed electroencephalography variables (reactivity,
continuity, epileptiform features, and prespecified "benign" or "highly
malignant" patterns based on the American Clinical Neurophysiology Society
nomenclature) and other clinical, neurophysiologic (somatosensory-evoked
potential), and biochemical prognosticators. Good outcome (Cerebral Performance
Categories 1 and 2) and mortality predictions at 3 months were calculated. Among
357 patients, early electroencephalography reactivity and continuity and flexor
or better motor reaction had greater than 70% positive predictive value for good
outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95%
CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography
heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for
mortality were less than 5% for epileptiform or nonreactive early
electroencephalography, nonreactive late electroencephalography, absent
somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of
myoclonus, and neuron-specific enolase greater than 75 ug/L; accuracy was highest
for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early
highly malignant electroencephalography had an false positive rate of 1.5% with
accuracy of 85.7% (95% CI, 81.7-89.2%). CONCLUSIONS: This study provides class
III evidence that electroencephalography reactivity predicts both poor and good
outcomes, and motor reaction good outcome after cardiac arrest.
Electroencephalography reactivity seems to be the best discriminator between good
and poor outcomes. Standardized electroencephalography interpretation seems to
predict both conditions during and after targeted temperature management.
PMID- 28406810
TI - New Developments in Minimally Invasive Gynecologic Oncology Surgery.
AB - Minimally invasive surgery continues to transform the field of gynecologic
oncology and has now become the standard of care for many early-stage
malignancies. The proven benefits of minimally invasive surgery are driving the
rapid introduction and dissemination of novel technologies and the increasing
ability to perform even the most complex procedures less invasively. In this
article, we will review the current literature on traditional multiport
laparoscopy, robotic-assisted laparoscopy, laparoendoscopic single-site surgery
as well as robotic-assisted laparoendoscopic single-site surgery, with a specific
focus on their role in the treatment of gynecologic malignancies.
PMID- 28406813
TI - Effects of Hypercapnia and Hypercapnic Acidosis on Hospital Mortality in
Mechanically Ventilated Patients.
AB - OBJECTIVES: Lung-protective ventilation is used to prevent further lung injury in
patients on invasive mechanical ventilation. However, lung-protective ventilation
can cause hypercapnia and hypercapnic acidosis. There are no large clinical
studies evaluating the effects of hypercapnia and hypercapnic acidosis in
patients requiring mechanical ventilation. DESIGN: Multicenter, binational,
retrospective study aimed to assess the impact of compensated hypercapnia and
hypercapnic acidosis in patients receiving mechanical ventilation. SETTINGS: Data
were extracted from the Australian and New Zealand Intensive Care Society Centre
for Outcome and Resource Evaluation Adult Patient Database over a 14-year period
where 171 ICUs contributed deidentified data. PATIENTS: Patients were classified
into three groups based on a combination of pH and carbon dioxide levels
(normocapnia and normal pH, compensated hypercapnia [normal pH with elevated
carbon dioxide], and hypercapnic acidosis) during the first 24 hours of ICU stay.
Logistic regression analysis was used to identify the independent association of
hypercapnia and hypercapnic acidosis with hospital mortality. INTERVENTIONS: Nil.
MEASUREMENTS AND MAIN RESULTS: A total of 252,812 patients (normocapnia and
normal pH, 110,104; compensated hypercapnia, 20,463; and hypercapnic acidosis,
122,245) were included in analysis. Patients with compensated hypercapnia and
hypercapnic acidosis had higher Acute Physiology and Chronic Health Evaluation
III scores (49.2 vs 53.2 vs 68.6; p < 0.01). The mortality was higher in
hypercapnic acidosis patients when compared with other groups, with the lowest
mortality in patients with normocapnia and normal pH. After adjusting for
severity of illness, the adjusted odds ratio for hospital mortality was higher in
hypercapnic acidosis patients (odds ratio, 1.74; 95% CI, 1.62-1.88) and
compensated hypercapnia (odds ratio, 1.18; 95% CI, 1.10-1.26) when compared with
patients with normocapnia and normal pH (p < 0.001). In patients with hypercapnic
acidosis, the mortality increased with increasing PCO2 until 65 mm Hg after which
the mortality plateaued. CONCLUSIONS: Hypercapnic acidosis during the first 24
hours of intensive care admission is more strongly associated with increased
hospital mortality than compensated hypercapnia or normocapnia.
PMID- 28406814
TI - Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute
Respiratory Distress Syndrome.
AB - OBJECTIVES: Prior studies suggest hypothermia may be beneficial in acute
respiratory distress syndrome, but cooling causes shivering and increases
metabolism. The objective of this study was to assess the feasibility of
performing a randomized clinical trial of hypothermia in patients with acute
respiratory distress syndrome receiving treatment with neuromuscular blockade
because they cannot shiver. DESIGN: Retrospective study and pilot, prospective,
open-label, feasibility study. SETTING: Medical ICU. PATIENTS: Retrospective
review of 58 patients with acute respiratory distress syndrome based on Berlin
criteria and PaO2/FIO2 less than 150 who received neuromuscular blockade.
Prospective hypothermia treatment in eight acute respiratory distress syndrome
patients with PaO2/FIO2 less than 150 receiving neuromuscular blockade.
INTERVENTION: Cooling to 34-36 degrees C for 48 hours. MEASUREMENTS AND MAIN
RESULTS: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F
were sequentially measured, and medians (interquartile ranges) presented, 28-day
ventilator-free days, and hospital mortality were calculated in historical
controls and eight cooled patients. Average patient core temperature was 36.7
degrees C (36-37.3 degrees C), and fever occurred during neuromuscular blockade
in 30 of 58 retrospective patients. In the prospectively cooled patients, core
temperature reached target range less than or equal to 4 hours of initiating
cooling, remained less than 36 degrees C for 92% of the 48 hours cooling period
without adverse events, and was lower than the controls (34.35 degrees C [34-34.8
degrees C]; p < 0.0001). Compared with historical controls, the cooled patients
tended to have lower hospital mortality (75% vs 53.4%; p = 0.26), more ventilator
free days (9 [0-21.5] vs 0 [0-12]; p = 0.16), and higher day 3 P/F (255 [160-270]
vs 171 [120-214]; p = 0.024). CONCLUSIONS: Neuromuscular blockade alone does not
cause hypothermia but allowed acute respiratory distress syndrome patients to be
effectively cooled. Results support conducting a randomized clinical trial of
hypothermia in acute respiratory distress syndrome and the feasibility of
studying acute respiratory distress syndrome patients receiving neuromuscular
blockade.
PMID- 28406815
TI - Massei Primary Periosteoplasty.
PMID- 28406818
TI - Reply: Secondary Alveolar Bone Grafting or Primary Periosteoplasty?
PMID- 28406820
TI - Sometimes It's Not Your Fault.
PMID- 28406821
TI - Vascularized Lymph Node Transfer to the Profunda Artery Perforator Pedicle: A
Reliable Proximal Recipient Vessel Option in the Medial Thigh.
PMID- 28406822
TI - The Delay Phenomenon in the Setting of Prior Irradiation: A Matched-Pair Analysis
in Nipple Reconstruction.
PMID- 28406824
TI - Ultrasound-Assisted Lymphaticovenular Anastomosis for the Treatment of Peripheral
Lymphedema.
PMID- 28406825
TI - Reply: Outcome Evaluation after 2023 Nipple-Sparing Mastectomies: Our Experience.
PMID- 28406826
TI - The Lipo-Body Lift: A New Circumferential Body-Contouring Technique Useful after
Bariatric Surgery.
PMID- 28406827
TI - Outcome Evaluation after 2023 Nipple-Sparing Mastectomies: Our Experience.
PMID- 28406829
TI - Reply: The Lipo-Body Lift: A New Circumferential Body-Contouring Technique Useful
after Bariatric Surgery.
PMID- 28406831
TI - Healthcare survival in a flat world: Creating your "special sauce".
PMID- 28406832
TI - Using transvaginal ultrasound to determine the cause of chronic pelvic pain.
PMID- 28406833
TI - Hepatitis C infection: Updates on treatment guidelines.
PMID- 28406834
TI - Caring for military families: Understanding their unique stressors.
PMID- 28406835
TI - Pediatric portal hypertension: A review for primary care.
AB - Pediatric portal hypertension management is a team approach between the patient,
the patient's family, the primary caregiver, and specialty providers. Evidence
based practice guidelines have not been established in pediatrics. This article
serves as a review for the primary care NP in the management of pediatric portal
hypertension, discussing the etiology, pathophysiology, and clinical presentation
of pediatric portal hypertension, diagnostic tests, and treatment and management
options.
PMID- 28406836
TI - Transitioning newly diagnosed patients with HIV into care.
AB - Fewer than half of the individuals in the United States with HIV are receiving
the full benefit of treatment. Primary care providers play a pivotal role in
creating a pipeline into HIV care following diagnosis. Using interview data and
current literature, this article provides recommendations for promoting care
initiation for individuals newly diagnosed with HIV.
PMID- 28406838
TI - Managing acute bacterial skin and skin structure infections: Focus on new
lipoglycopeptides.
AB - Acute bacterial skin and skin structure infections (ABSSSI) are some of the most
commonly encountered infections worldwide. Hospitalizations as a result of ABSSSI
are associated with high mortality. This article discusses the role of
oritavancin and dalbavancin, two new lipoglycopeptides, in the context of the
other I.V. available standard therapy options.
PMID- 28406839
TI - Self-Identity After Bereavement: Reduced Self-Clarity and Loss-Centrality in
Emotional Problems After the Death of a Loved One.
AB - There is evidence that both the centrality of a loss-event as well as reduced
self-concept clarity are involved in emotional problems after the death of a
loved one. One issue that is still unexplored is the relative importance of these
two concepts in predicting bereavement outcome. The current study examined the
degree to which both concepts contribute to emotional distress after loss, both
concurrently and longitudinally. Data were available from 124 individuals, all
bereaved within the previous half year, who completed measures of prolonged
grief, posttraumatic stress, and depression at inclusion into the study and again
6 months later. Loss-centrality and self-unclarity were associated with all three
outcome measures, in cross-sectional analyses. Longitudinal analyses indicated
that loss-centrality predicted symptom levels of prolonged grief, self-unclarity
predicted symptom levels of depression, and both loss-centrality and self
unclarity were associated with posttraumatic stress 6 months after baseline.
Implications of these findings are discussed.
PMID- 28406840
TI - Association Between Vitamin D Status and Schizophrenia: A First Psychotic Episode
Study.
AB - Vitamin D deficiency has been linked with schizophrenia. We aimed to determine
whether patients with a first episode of psychosis (FEP) had lower vitamin D
levels compared with controls considering their final diagnosis. We conducted a
cross-sectional study determining 25-hydroxyvitamin D blood levels. 25
Hydroxyvitamin D levels were considered optimum at 20 ng/mL or greater. A group
of 45 adult patients with FEP and a group of 22 healthy controls matched for age
were recruited. The patient group was subdivided in two final diagnosis groups
(schizophrenia versus other psychoses) after a 6-month follow-up. Average vitamin
D values were deficient for FEP patients, especially those 22 with a final
diagnosis of schizophrenia. These results relating vitamin D and schizophrenia
generate interest to further examine this association.
PMID- 28406841
TI - Deception in Medicine: Hermes or Asclepius?
PMID- 28406842
TI - HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.
AB - Iron participates in oxygen transport, energetic, metabolic, and immunologic
processes. There are 2 main causes of iron overload: hereditary hemochromatosis
which is a primary cause, is a metabolic disorder caused by mutations of genes
that control iron metabolism and secondary hemochromatosis caused by
multitransfusions, chronic hemolysis, and intake of iron rich food. The most
common type of hereditary hemochromatosis is caused by HFE gene mutation. In this
study, we analyzed iron metabolism in 100 healthy Polish children in relation to
their HFE gene status. The wild-type HFE gene was predominant being observed in
60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D
mutation, and 15 children (15%), presented with other mutations (heterozygotic
C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D
homozygote). The mean concentration of iron, the level of ferritin, and
transferrin saturation were statistically higher in the group of HFE variants
compared with the wild-type group. H63D carriers presented with higher mean
concentration of iron, ferritin levels, and transferrin saturation compared with
the wild-type group. Male HFE carriers presented with higher iron concentration,
transferrin saturation, and ferritin levels than females. This preliminary
investigation demonstrates allelic impact on potential disease progression from
childhood.
PMID- 28406843
TI - Analyzing Patient Safety Culture From Viewpoints of Physicians and Nurses-A Case
of a Regional Teaching Hospital in Taiwan.
AB - The Chinese version of safety attitudes questionnaire is used to evaluate patient
safety culture from the viewpoints of physicians and nurses of a regional
teaching hospital in Taiwan in 2014. This study applies Mann-Whitney U test for
two independent samples test and analysis of variance to observe if different
demographic variables are perceived differently in patient safety culture in
terms of eight dimensions. In addition, linear regression models are applied to
take into account the confounding effects of demographic variables in eight
dimensions. The results show that none of the eight dimensions is more important.
Besides, supervisor/manager and experience in position are the two critical
demographic variables to influence the patient safety culture. The results imply
that the hospital management needs to pay much attention to the employees who are
not supervisors/managers and/or more experienced in position because they are
less satisfied in patient safety culture.
PMID- 28406844
TI - The Role of HE4, a Novel Biomarker, in Predicting Optimal Cytoreduction After
Neoadjuvant Chemotherapy in Advanced Ovarian Cancer.
AB - OBJECTIVES: This study aimed to evaluate serum human epididymis protein 4 (HE4)
changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking
surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography
(CT) taken together are better able to predict complete cytoreduction after NACT
in advanced ovarian cancer patients. METHODS: From January 2006 to November 2015,
patients affected by epithelial advanced ovarian cancer (International Federation
of Gynecology and Obstetrics stage III-IV), considered not optimally resectable,
were included in this prospective study. After 3 cycles of NACT, all patients
underwent debulking surgery and were allocated, according to residual tumor (RT),
into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were
recorded during NACT and compared singularly and with each other in term of
accuracy, sensitivity, specificity, and positive and negative predictive value.
RESULTS: A total of 94 and 20 patients were included in group A and group B,
respectively. The HE4 values recorded before debulking surgery correlated with
RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify
patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and
a specificity of 85% (positive predictive value, 0.87; negative predictive value,
0.70). The combination of CA125, HE4, and CT imaging resulted in the best
combination with a sensitivity of 96% and a specificity of 92% (positive
predictive value, 0.96; negative predictive value, 0.94). CONCLUSIONS: The novel
biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at
debulking surgery and the prognosis of patients.
PMID- 28406845
TI - Heterogeneity in 14-year Dementia Incidence Between Asian American Subgroups.
AB - BACKGROUND: Asian Americans are a rapidly growing and diverse population. Prior
research on dementia among Asian Americans focused on Japanese Americans or Asian
Americans overall, although marked differences in cardiometabolic conditions
between subgroups have been documented. MATERIALS AND METHODS: We compared
dementia incidence among 4 Asian American subgroups (n=8384 Chinese; n=4478
Japanese; n=6210 Filipino; n=197 South Asian) and whites (n=206,490) who were
Kaiser Permanente Northern California members aged 64 years and above with no
dementia diagnoses as of January 1, 2000. Dementia diagnoses were collected from
medical records January 1, 2000 to December 31, 2013. Baseline medical
utilization and comorbidities (diabetes, depression, hypertension, stroke,
cardiovascular disease) were abstracted from medical records January 1, 1996 to
December 31, 1999. We calculated age-standardized dementia incidence rates and
Cox models adjusted for age, sex, medical utilization, and comorbidities.
RESULTS: Mean baseline age was 71.7 years; mean follow-up was 9.6 years. Age
standardized dementia incidence rates were higher among whites than "All Asian
Americans" or any subgroup. Compared with Chinese (13.7/1000 person-years),
dementia incidence was slightly higher among Japanese [14.8/1000 person-years;
covariate-adjusted hazard ratio (adjusted-HR)=1.08; 95% confidence interval (CI),
0.99-1.18] and Filipinos (17.3/1000 person-years; adjusted-HR=1.20; 95% CI, 1.11
1.31), and lower among South Asians (12.1/1000 person-years; adjusted-HR=0.81;
95% CI, 0.53-1.25). CONCLUSIONS: Future studies are needed to understand how
immigration history, social, environmental, and genetic factors contribute to
dementia risk in the growing and diverse Asian American population.
PMID- 28406846
TI - The value of simulation-based training in the path to laparoscopic urological
proficiency.
AB - PURPOSE OF REVIEW: Numerous factors have reduced the training opportunities of
surgical residents in the operating room. There is also the question of patient's
safety. This gives a need for increased training opportunities outside the
operating room. We look if there is an added value in simulation-based training
(SBT) in the acquisition of laparoscopic skills. RECENT FINDINGS: Incorporating
SBT into the medical students curriculum reduces surgical complication rates in
the operating room. SUMMARY: Reduction in opportunities to train surgical skills
in the operating room, increased complexity of surgical procedures, and justified
concerns for patients' safety require training opportunities outside the
operating room. Data proves that skills, acquired in the lab during SBT, are
transferable to the operating room. Moreover, incorporating an evidence-based
laparoscopic simulation curriculum shortens the clinical learning curve and
reduces surgical adverse events.
PMID- 28406847
TI - Nontechnical skill training and the use of scenarios in modern surgical
education.
AB - PURPOSE OF REVIEW: Nontechnical skills are being increasingly recognized as a
core reason of surgical errors. Combined with the changing nature of surgical
training, there has therefore been an increase in nontechnical skill research in
the literature. This review therefore aims to: define nontechnical skillsets,
assess current training methods, explore assessment modalities and suggest future
research aims. RECENT FINDINGS: The literature demonstrates an increasing
understanding of the components of nontechnical skills within surgery. This has
led to a greater availability of validated training methods for its training,
including the use of didactic teaching, e-learning and simulation-based
scenarios. In addition, there are now various extensively validated assessment
tools for nontechnical skills including NOTSS, the Oxford NOTECHS and OTAS.
Finally, there is now more focus on the development of tools which target
individual nontechnical skill components and an attempt to understand which of
these play a greater role in specific procedures such as laparoscopic or robotic
surgery. SUMMARY: Current evidence demonstrates various training methods and
tools for the training of nontechnical skills. Future research is likely to focus
increasingly on individual nontechnical skill components and procedure-specific
skills.
PMID- 28406848
TI - Clinical Validation of a Sound Processor Upgrade in Direct Acoustic Cochlear
Implant Subjects.
AB - OBJECTIVE: The objectives of the investigation were to evaluate the effect of a
sound processor upgrade on the speech reception threshold in noise and to collect
long-term safety and efficacy data after 21/2 to 5 years of device use of direct
acoustic cochlear implant (DACI) recipients. STUDY DESIGN: The study was designed
as a mono-centric, prospective clinical trial. SETTING: Tertiary referral center.
PATIENTS: Fifteen patients implanted with a direct acoustic cochlear implant.
INTERVENTION: Upgrade with a newer generation of sound processor. MAIN OUTCOME
MEASURES: Speech recognition test in quiet and in noise, pure tone thresholds,
subject-reported outcome measures. RESULTS: The speech recognition in quiet and
in noise is superior after the sound processor upgrade and stable after long-term
use of the direct acoustic cochlear implant. The bone conduction thresholds did
not decrease significantly after long-term high level stimulation. CONCLUSIONS:
The new sound processor for the DACI system provides significant benefits for
DACI users for speech recognition in both quiet and noise. Especially the noise
program with the use of directional microphones (Zoom) allows DACI patients to
have much less difficulty when having conversations in noisy environments.
Furthermore, the study confirms that the benefits of the sound processor upgrade
are available to the DACI recipients even after several years of experience with
a legacy sound processor. Finally, our study demonstrates that the DACI system is
a safe and effective long-term therapy.
PMID- 28406849
TI - Current Management Practices in Meniere's Disease.
AB - OBJECTIVE: To evaluate current trends in managing Meniere's disease (MD) by both
general otolaryngologists and otologists/neurotologists and discuss treatment
modalities. STUDY DESIGN: Cross-sectional study. SETTING: Survey of physicians.
SUBJECTS AND METHODS: An electronic questionnaire was disseminated to all members
of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). RESULTS:
Eight hundred and sixty members replied for a response rate of 14.5% for
generalists and 35% for neurotologists. Thirty-nine percent of respondents think
that diet and lifestyle changes are effective in controlling symptoms in more
than 50% of their MD patients. Overall, 72.8% of respondents used
hydrochlorothiazide/triamterene (HCTZ/TAT) "often" or "always" with
neurotologists using HCTZ/TAT more often than generalists (p < 0.001). Half of
neurotologists used IT steroids "often" or "always," compared with only 10% of
generalists (p < 0.001). Endolymphatic sac procedures are the most common
surgeries and are used more often by neurotologists than by generalists (p <
0.001). The Medtronic Meniett device is used more by neurotologists (p < 0.001)
but it is not commonly used overall (69.2% "never" use). CONCLUSION: Many options
are available for the treatment of MD. Neurotologists tend to use a wider variety
of medications in their treatment protocols than generalists. Neurotologists tend
to perform surgical interventions more frequently than generalists. Our evidence
shows significant heterogeneity for treatment of Meniere's disease among
otolaryngologists. A guideline that outlines appropriate therapeutic options,
dosing, and treatment escalation is warranted.
PMID- 28406850
TI - In Response to: Secondary Causes of Dizziness in Patients With MEniEre's Disease.
PMID- 28406851
TI - In Reply to the Letter to the Editor: "Two Common Second Causes of Dizziness in
Patients With MEniEre's Disease.
PMID- 28406852
TI - Survivorship After High-Energy Geriatric Trauma.
AB - OBJECTIVES: To evaluate in-hospital, 1-year, and 5-year survivorship of geriatric
patients after high-energy trauma, to compare survivorship of geriatric patients
who sustained high-energy trauma with that of those who sustained low-energy
trauma, and to identify predictors for mortality. DESIGN: Retrospective. SETTING:
Urban Level I trauma center. PATIENTS: Study group of 1849 patients with high
energy trauma and comparison group of 761 patients with low-energy trauma.
INTERVENTION: Each patient was observed from the time of index admission through
the end of the study period or until death or readmission. MAIN OUTCOME
MEASUREMENT: Long-term survivorship based on the Social Security Death Index.
RESULTS: Survivorship between patients with high-energy and low-energy injuries
was statistically significant. Among patients who sustained high-energy injuries,
in-hospital mortality was 8%, 1-year mortality was 15%, and 5-year mortality was
25%. Among patients who sustained low-energy injuries, in-hospital mortality was
3%, 1-year mortality was 23%, and 5-year mortality was 40%. Low-energy mechanism
of injury was an independent predictor for 1-year and 5-year mortality, even when
controlling for Charlson Comorbidity Index (CCI), Injury Severity Score (ISS),
age, sex, body mass index (BMI), and admission Glasgow Coma Scale (GCS) score.
CONCLUSIONS: Geriatric patients with high-energy injuries and those with low
energy injuries seem to represent different patient populations, and low-energy
mechanism seems to be a marker for frailty. High-energy mechanism was associated
with lower long-term mortality rates, even when controlling for CCI, ISS, age,
sex, BMI and admission GCS score. LEVEL OF EVIDENCE: Prognostic Level III. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 28406854
TI - Invited Commentary related to: Tranexamic Acid Safely Reduced Blood Lossin Hemi-
and Total Hip Arthroplasty for Acute Femoral Neck Fracture: A Randomized Clinical
Trial.
PMID- 28406855
TI - Beyond the Treatment Box: Perspectives on the Federal Response to Opioid Use,
Pregnancy, and Neonatal Abstinence Syndrome.
AB - : There has been much activity within Federal agencies in response to the opioid
epidemic particularly in regards to pregnant women and their infants. Substance
Abuse and Mental Health Services Administration's recently released document,
Advancing the Care of Pregnant and Parenting Women With Opioid Use Disorder and
Their Infants: A Foundation for Clinical Guidance, provides an important and
timely guidance. Uptake of the guide should improve quality of care and hopefully
help lessen the discrimination experienced by pregnant women with opioid use
disorder. However, most pregnant women with addiction do not have access to
treatment. This unmet need is large and vexing and only tangentially addressed in
the Guide. Future Federal efforts should focus beyond the "treatment box."
PMID- 28406857
TI - Spectacle Compliance among Adolescents: A Qualitative Study from Southern India.
AB - PURPOSE: To understand the perceptions of adolescents and their parents about
spectacle compliance of adolescents in Southern India. METHODS: Using a
qualitative snapshot design, three focus group discussions were conducted each
with parents and adolescents studying in schools located in and around Chennai,
Tamil Nadu. Purposive sampling technique was used in the selection of
participants. Separate focus group guides were developed for parents and
adolescents. All focus group discussions were conducted in the school premises
and audio recorded. These audio files were then transcribed verbatim and then
translated into English. A framework analytical approach was used for data
analysis that involved gaining familiarity with the data to identify a thematic
framework. RESULTS: Two major themes that emerged were (1) perceptions on
barriers to spectacle compliance that was further subdivided into physical,
psychological, and societal barriers; and (2) solutions to improve spectacle use.
Barriers identified included scars on the nose, unattractive frames contributing
to poor appeal, adolescents feeling discriminated and set apart, fears of injury
to eyes, lack of parental involvement, and negative attitudes of society toward
those wearing spectacles. Solutions given by the stakeholders included provision
of lightweight, well-fitting, trendy frames of adolescents' choice, importance
and need for periodical eye examinations, including teachers in encouraging
spectacle use and preventing bullying and teasing by other adolescents, provision
of free spectacles along with periodic replacement, and inclusion of awareness
sessions on spectacle use for both parents and adolescents. CONCLUSIONS: The
study has identified both barriers and solutions for improving spectacle
compliance among school adolescents from the viewpoint of the stakeholders
involved. Implementing the solutions suggested by the stakeholders through
planned intervention programs could possibly help in ensuring better compliance
of spectacle use among school adolescents.
PMID- 28406856
TI - Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the
Concurrent Care of Their Infants and Children: Literature Review to Support
National Guidance.
AB - OBJECTIVES: The prevalence of opioid use disorder (OUD) during pregnancy is
increasing. Practical recommendations will help providers treat pregnant women
with OUD and reduce potentially negative health consequences for mother, fetus,
and child. This article summarizes the literature review conducted using the
RAND/University of California, Los Angeles Appropriateness Method project
completed by the US Department of Health and Human Services Substance Abuse and
Mental Health Services Administration to obtain current evidence on treatment
approaches for pregnant and parenting women with OUD and their infants and
children. METHODS: Three separate search methods were employed to identify peer
reviewed journal articles providing evidence on treatment methods for women with
OUD who are pregnant or parenting, and for their children. Identified articles
were reviewed for inclusion per study guidelines and relevant information was
abstracted and summarized. RESULTS: Of the 1697 articles identified, 75 were
included in the literature review. The perinatal use of medication for addiction
treatment (MAT, also known as medication-assisted treatment), either methadone or
buprenorphine, within comprehensive treatment is the most accepted clinical
practice, as withdrawal or detoxification risks relapse and treatment dropout.
Medication increases may be needed with advancing pregnancy, and are not
associated with more severe neonatal abstinence syndrome (NAS). Switching
medication prenatally is usually not recommended as it can destabilize opioid
abstinence. Postnatally, breastfeeding is seen as beneficial for the infant for
women who are maintained on a stable dose of opioid agonist medication. Less is
known about ideal pain management and postpartum dosing regimens. NAS appears
generally less severe following prenatal exposure to buprenorphine versus
methadone. Frontline NAS medication treatments include protocol-driven methadone
and morphine dosing in the context of nonpharmacological supports. CONCLUSIONS:
Women with OUD can be treated with methadone or buprenorphine during pregnancy.
NAS is an expected and manageable condition. Although research has substantially
advanced, opportunities to guide future research to improve maternal and infant
outcomes are provided.
PMID- 28406858
TI - INVOLVEMENT OF MULTIPLE MOLECULAR PATHWAYS IN THE GENETICS OF OCULAR REFRACTION
AND MYOPIA.
AB - PURPOSE: The prevalence of myopia has increased dramatically worldwide within the
last three decades. Recent studies have shown that refractive development is
influenced by environmental, behavioral, and inherited factors. This review aims
to analyze recent progress in the genetics of refractive error and myopia.
METHODS: A comprehensive literature search of PubMed and OMIM was conducted to
identify relevant articles in the genetics of refractive error. RESULTS: Genome
wide association and sequencing studies have increased our understanding of the
genetics involved in refractive error. These studies have identified interesting
candidate genes. All genetic loci discovered to date indicate that refractive
development is a heterogeneous process mediated by a number of overlapping
biological processes. The exact mechanisms by which these biological networks
regulate eye growth are poorly understood. Although several individual genes
and/or molecular pathways have been investigated in animal models, a systematic
network-based approach in modeling human refractive development is necessary to
understand the complex interplay between genes and environment in refractive
error. CONCLUSION: New biomedical technologies and better-designed studies will
continue to refine our understanding of the genetics and molecular pathways of
refractive error, and may lead to preventative and therapeutic measures to combat
the myopia epidemic.
PMID- 28406859
TI - VISUAL ACUITY IMPROVEMENT WHEN SWITCHING FROM RANIBIZUMAB TO AFLIBERCEPT IS NOT
SUSTAINED.
AB - PURPOSE: To assess whether visual benefits exist in switching to aflibercept in
patients who have been chronically treated with ranibizumab for neovascular age
related macular degeneration. METHODS: A multicenter, national, electronic
medical record database study was performed. Patients undergoing six continuous
monthly ranibizumab injections and then switched to continuous aflibercept were
matched to those on continuous ranibizumab therapy. Matching was performed in a
2:1 ratio and based on visual acuity 6 months before and at the time of the
switch, and the number of previous ranibizumab injections. RESULTS: Patients who
were switched to aflibercept demonstrated transiently significant improvement in
visual acuity that peaked at an increase of 0.9 Early Treatment Diabetic
Retinopathy Study letters 3 months after the switch, whereas control patients
continued on ranibizumab treatment showed a steady decline in visual acuity.
Visual acuity differences between the groups were significant (P < 0.05) at 2, 3,
and 5 months after the switch. Beginning at 4 months after the switch, the switch
group showed a visual acuity decline similar to the control group. CONCLUSION:
Transient, nonsustained improvement in visual acuity occurs when switching
between anti-vascular endothelial growth factor agents, which may have
implications in treating patients on chronic maintenance therapy on one anti
vascular endothelial growth factor medication.
PMID- 28406860
TI - PREDICTIVE VALUE OF OPTICAL COHERENCE TOMOGRAPHIC FEATURES IN THE BEVACIZUMAB AND
RANIBIZUMAB IN PATIENTS WITH DIABETIC MACULAR EDEMA (BRDME) STUDY.
AB - PURPOSE: To establish the predictive value of specific optical coherence
tomography retinal features on visual outcomes and retinal thickness during anti
vascular endothelial growth factor treatment in patients with diabetic macular
edema. METHODS: Post hoc analysis of compound data of a prospective, 6-month,
multicenter, randomized controlled trial of 119 patients with diabetic macular
edema receiving either intravitreal bevacizumab or ranibizumab were analyzed to
assess the associations between baseline retinal morphologic parameters and
change in best-corrected visual acuity and central subfield thickness. Based on
the study protocol of the core study, best-corrected visual acuity and central
subfield thickness were obtained before each mandatory monthly injection during 6
months. RESULTS: The presence of serous retinal detachment at baseline was
associated with significant improvement in best-corrected visual acuity letter
score at Month 3 and Month 6 (P < 0.001 and P = 0.01, respectively). In addition,
the presence of disorganization of retinal inner layers was associated with lower
best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.05 and P
= 0.01, respectively). CONCLUSION: This study found that serous retinal
detachment and disorganization of retinal inner layers were associated with
different treatment responses to anti-vascular endothelial growth factor therapy
in patients with diabetic macular edema.
PMID- 28406861
TI - CLINICAL PRESENTATION, MICROBIOLOGIC PROFILE AND FACTORS PREDICTING OUTCOMES IN
BACILLUS ENDOPHTHALMITIS.
AB - PURPOSE: To describe the clinical presentation, microbiologic profile, and
factors predicting outcomes in Bacillus endophthalmitis. METHODS: Retrospective
interventional case series. Eighty-six patients with culture-proven Bacillus
endophthalmitis, from January 2001 to December 2015, underwent
vitrectomy/vitreous biopsy and intravitreal antibiotic with or without steroid as
appropriate. The undiluted vitreous biopsy was subjected to microbiologic
evaluation. The duration of symptoms, presenting visual acuity, organisms
isolated, influence of intravitreal dexamethasone with intravitreal antibiotics,
and type of initial intervention were examined for any clinical and statistical
correlation in terms of odds ratio with the final visual outcome. RESULTS: Trauma
was the commonest etiology (n = 75; 87.2%). Mixed infection with other bacteria
was seen in 11 patients. All Bacillus species were sensitive to gentamicin
followed by ciprofloxacin (n = 85; 98.83%) and vancomycin (n = 81; 94.18%). Odds
in favor of a favorable visual outcome were seen with clinical treatment within
48 hours of the symptoms (OR 25.47, 95% CI 2.45-254.16, P = 0.006), better
presenting vision (OR 31.21, 95% CI 2.96-323.64, P = 0.004), and absence of
polymicrobial infection (OR 18.03, 95% CI 0.9-344.4, P = 0.05). Only 20% of all
treated patients regained ambulatory vision, and one fifth of all of them
developed phthisis. CONCLUSION: Patients diagnosed with Bacillus endophthalmitis
merit aggressive vitreous intervention guided by the culture-sensitivity report.
Despite early and appropriate treat ment, the outcomes are generally poor.
PMID- 28406864
TI - Multistep Approach for Improved Aesthetic and Functional Outcomes for Lower
Extremity Wound Closure After Mohs Micrographic Surgery.
AB - BACKGROUND: Lower extremity wounds present a major clinical challenge. OBJECTIVE:
This paper introduces a new multistep approach for improved aesthetic and
functional outcome for lower extremity wound closure after Mohs micrographic
surgery. PATIENTS AND METHODS: In this prospective case series, 12 consecutive
patients undergoing Mohs micrographic surgery for cutaneous malignancies of the
lower extremities underwent closure assisted by elastic bandages, proper
positioning with 45 degrees flexion of the knee, buried vertical mattress
sutures, and careful eversion, using a premium angled stapler. Assessment of
cosmetic outcome was performed by 2 blinded observers, using the Hollander Wound
Evaluation Scale. RESULTS: The mean age was 73 +/- 9 years with most patients
having at least one comorbidity. Six patients (50%) underwent resection of a
basal cell carcinoma and 5 patients (42%) underwent resection of a squamous cell
carcinoma and 1 patient (8%) underwent resection of a keratoacanthomatous
carcinoma. There were no wound complications, and at the 3- to 6-month follow-up,
11 of the 12 wounds (92%) had an optimal Hollander Wound Evaluation Scale score
of 6. CONCLUSION: This new approach to lower extremity wounds provides excellent
cosmetic outcome with no reported complications.
PMID- 28406862
TI - A Randomized Controlled Trial of Corticosteroids in Pediatric Septic Shock: A
Pilot Feasibility Study.
AB - OBJECTIVE: To determine the feasibility of conducting a randomized controlled
trial of corticosteroids in pediatric septic shock. DESIGN: Randomized, double
blind, placebo controlled trial. SETTING: Seven tertiary level PICUs in Canada.
PATIENTS: Children newborn to 17 years old inclusive with suspected septic shock.
INTERVENTION: Administration of IV hydrocortisone versus placebo until
hemodynamic stability is achieved or for a maximum of 7 days. MEASUREMENTS AND
MAIN RESULTS: One hundred seventy-four patients were potentially eligible of whom
101 patients met eligibility criteria. Fifty-seven patients were randomized, and
49 patients (23 and 26 patients in the hydrocortisone and placebo groups,
respectively) were included in the final analysis. The mean time from screening
to randomization was 2.4 +/- 2.1 hours and from screening to first dose of study
drug was 3.8 +/- 2.6 hours. Forty-two percent of potentially eligible patients
(73/174) received corticosteroids prior to randomization: 38.5% (67/174) were
already on corticosteroids for shock at the time of screening, and in 3.4%
(6/174), the treating physician wished to administer corticosteroids. Six of 49
randomized patients (12.2%) received open-label steroids, three in each of the
hydrocortisone and placebo groups. Time on vasopressors, days on mechanical
ventilation, PICU and hospital length of stay, and the rate of adverse events
were not statistically different between the two groups. CONCLUSIONS: This study
suggests that a large randomized controlled trial on early use of corticosteroids
in pediatric septic shock is potentially feasible. However, the frequent use of
empiric corticosteroids in otherwise eligible patients remains a significant
challenge. Knowledge translation activities, targeted recruitment, and
alternative study designs are possible strategies to mitigate this challenge.
PMID- 28406863
TI - Fluid Overload and Kidney Injury Score: A Multidimensional Real-Time Assessment
of Renal Disease Burden in the Critically Ill Patient.
AB - OBJECTIVE: Interruptive acute kidney injury alerts are reported to decrease acute
kidney injury-related mortality in adults. Critically ill children have multiple
acute kidney injury risk factors; although recognition has improved due to
standardized definitions, subtle changes in serum creatinine make acute kidney
injury recognition challenging. Age and body habitus variability prevent a
uniform maximum threshold of creatinine. Exposure of nephrotoxic medications is
common but not accounted for in kidney injury scores. Current severity of illness
measures do not include fluid overload, a well-described mortality risk factor.
We hypothesized that a multidimensional measure of renal status would better
characterize renal severity of illness while maintaining or improving on
correlation measures with adverse outcomes, when compared with traditional acute
kidney injury staging. DESIGN: A novel, real-time, multidimensional, renal status
measure, combining acute kidney injury, fluid overload greater than or equal to
15%, and nephrotoxin exposure, was developed (Fluid Overload Kidney Injury Score)
and prospectively applied to all patient encounters. Peak Fluid Overload Kidney
Injury Score values prior to discharge or death were used to measure correlation
with outcomes. SETTING: Quarternary PICU of a freestanding children's hospital.
PATIENTS: All patients admitted over 18 months. INTERVENTION: None. RESULTS: Peak
Fluid Overload Kidney Injury Score ranged between 0 and 14 in 2,830 PICU patients
(median age, 5.5 yr; interquartile range, 1.3-12.9; 55% male), 66% of patients
had Fluid Overload Kidney Injury Score greater than or equal to 1. Fluid Overload
Kidney Injury Score was independently associated with PICU mortality and PICU and
hospital length of stay when controlled for age, Pediatric Risk of Mortality-3,
ventilator, pressor, and renal replacement therapy use (p = 0.047). Mortality
increased from 1.5% in Fluid Overload Kidney Injury Score 0 to 40% in Fluid
Overload Kidney Injury Score 8+. When urine output points were excluded, Fluid
Overload Kidney Injury Score was more strongly correlated with mortality than
fluid overload or acute kidney injury definitions alone. CONCLUSION: A
multidimensional score of renal disease burden was significantly associated with
adverse PICU outcomes. Further studies will evaluate Fluid Overload Kidney Injury
Score as a warning and decision support tool to impact patient-centered outcomes.
PMID- 28406865
TI - Facilitating Microneedling Over the Cheeks.
PMID- 28406866
TI - Successful Treatment of a Residual, Thick, Infantile Hemangioma in a Darker
Phototype Pediatric Patient Using the 755-nm Long-Pulsed Alexandrite Laser.
PMID- 28406867
TI - Promoting Health Through the Internet and Social Media.
PMID- 28406868
TI - A Conversation With Robert J. Wicks, PsyD.
PMID- 28406869
TI - Concept Communication and Interpretation of Illness: A Holistic Model of
Understanding in Nursing Practice.
AB - To ensure patient communication in nursing, certain conditions must be met that
enable successful exchange of beliefs, thoughts, and other mental states. The
conditions that have received most attention in the nursing literature are
derived from general communication theories, psychology, and ethical frameworks
of interpretation. This article focuses on a condition more directly related to
an influential coherence model of concept possession from recent philosophy of
mind and language. The basic ideas in this model are (i) that the primary source
of understanding of illness experiences is communicative acts that express
concepts of illness, and (ii) that the key to understanding patients' concepts of
illness is to understand how they depend on patients' lifeworlds. The article
argues that (i) and (ii) are especially relevant in caring practice since it has
been extensively documented that patients' perspectives on disease and illness
are shaped by their subjective horizons. According to coherentism, nurses need to
focus holistically on patients' horizons in order to understand the meaning of
patients' expressions of meaning. Furthermore, the coherence model implies that
fundamental aims of understanding can be achieved only if nurses recognize the
interdependence of patients' beliefs and experiences of ill health. The article
uses case studies to elucidate how the holistic implications of coherentism can
be used as conceptual tools in nursing.
PMID- 28406870
TI - The Effect of Acupressure Applied to Point LI4 on Perceived Labor Pains.
AB - Controlling labor pain is one of the basic goals for caregivers during the
birthing process. There are many pharmacological and nonpharmacological methods
that are used for controlling pain and helping the mother to cope with pain and
have a favorable labor. The study was planned as a randomized, controlled
experimental study to detect the effect of acupressure applied to Point LI4 on
perceived labor pains. The study sample comprised 88 pregnant women (44
acupressure group, 44 control group), who complied with the study guidelines,
agreed with the conditions of the study, and signed the informed consent.
Acupressure was applied to the study group when cervical dilatation reached 4 to
5 cm and again when cervical dilation was 7 to 8 cm. Acupressure was applied to
Point LI4 on both the hands at the same time from the beginning to the end of the
contraction (16 times). Evaluation with the visual analog scale was made 6 times:
when the pregnant woman was first admitted to the hospital, before and after
acupressure, and within 2 hours after delivery. The control group received
routine care. There were statistically significant differences between the groups
in subjective labor pain scores (P < .0001). There was a significant difference
between the groups in terms of total duration of labor. As shown from our study,
applying acupressure to Point LI4 was found to be effective in decreasing the
perception of labor pains and shortening the labor (P < .05). Mothers were
pleased with this treatment, but they found it insufficient to control their
pain.
PMID- 28406871
TI - Effects of Breathing-Based Meditation on Earthquake-Affected Health
Professionals.
AB - On March 11, 2013, the Great East Japan Earthquake (magnitude 9) hit the northern
part of Japan (Tohoku), killing more than 15 000 people and leaving long-lasting
scars, including psychological damage among evacuees, some of whom were health
professionals. Little is known about meditation efficacy on disaster-affected
health professionals. The present study investigated the effects of breathing
based meditation on seminar participants who were health professionals who had
survived the earthquake. This study employed a mixed methods approach, using both
survey data and handwritten qualitative data. Quantitative results of pre- and
postmeditation practice indicated that all mood scales (anger, confusion,
depression, fatigue, strain, and vigor) were significantly improved (N = 17).
Qualitative results revealed several common themes (emancipation from chronic and
bodily senses; holistic sense: transcending mind-body; re-turning an axis in life
through reflection, self-control, and/or gratitude; meditation into mundane,
everyday life; and coming out of pain in the aftermath of the earthquake) that
had emerged as expressions of participant meditation experiences. Following the
45-minute meditation session, the present study participants reported
improvements in all psychological states (anger, confusion, depression, fatigue,
strain, and vigor) in the quantitative portion, which indicated efficacy of the
meditation. Our analysis of the qualitative portion revealed what and how
participants felt during meditating.
PMID- 28406872
TI - Assessing the Readiness of Nursing Sectors in Low- and Middle-Income Countries to
Adopt Holistic Practice: Rwanda as Exemplar.
AB - Over the past several years, holistic nursing education has become more readily
available to nurses working in high-income nations, and holistic practice has
become better defined and promoted through countless organizational and
governmental initiatives. However, global nursing community members, particularly
those serving in low- and middle-income countries (LMICs) within resource
constrained health care systems, may not find holistic nursing easily accessible
or applicable to practice. The purpose of this article is to assess the readiness
of nursing sectors within these resource-constrained settings to access,
understand, and apply holistic nursing principles and practices within the
context of cultural norms, diverse definitions of the nursing role, and the
current status of health care in these countries. The history, current status,
and projected national goals of professional nursing in Rwanda is used as an
exemplar to forward the discussion regarding the readiness of nurses to adopt
holistic education into practice in LMICs. A background of holistic nursing
practice in the United States is provided to illustrate the multifaceted aspects
of support necessary in order that such a specialty continues to evolve and
thrive within health care arenas and the communities it cares for.
PMID- 28406874
TI - The Microbiota-Obesity Connection, Part 2.
PMID- 28406873
TI - Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a
Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.
AB - As the use of herbal medications continues to increase in America, the potential
interaction between herbal and prescription medications necessitates the
discovery of their mechanisms of action. The purpose of this study was to
investigate the anxiolytic and antidepressant effects of curcumin, a compound
from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the
gamma-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective,
between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned
to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin,
curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing
was performed using the elevated plus maze, open field test, and forced swim
test. A 2-tailed multivariate analysis of variance and least significant
difference post hoc tests were used for data analysis. In our models, curcumin
did not demonstrate anxiolytic effects or changes in behavioral despair. An
interaction of curcumin at the benzodiazepine site of the GABAA receptor was also
not observed. Additional studies are recommended that examine the anxiolytic and
antidepressant effects of curcumin through alternate dosing regimens, modulation
of other subunits on the GABAA receptor, and interactions with other central
nervous system neurotransmitter systems.
PMID- 28406875
TI - Animal Proteins: Challenges and Opportunities Beyond "Avoiding Red Meat".
PMID- 28406876
TI - Cartilage Restoration Techniques for the Patellofemoral Joint.
AB - Symptomatic osteochondral lesions of the patellofemoral joint are clinically
challenging to manage because of the limited healing potential of articular
cartilage; the complex morphology of the patellofemoral joint; the heterogeneity
of the articular surface between patients; and high stresses across the joint,
which can be altered by malalignment, tilt, or maltracking. Indications for
surgery include traumatic lesions, osteochondritis dissecans, and high-grade
chondromalacia in association with persistent pain despite a course of
nonsurgical management. Various techniques have been described for managing
symptomatic osteochondral lesions of the patellofemoral joint, including
microfracture, osteochondral autograft transplantation, and biologic cell
transplantation, including autologous chondrocyte implantation. Salvage
techniques (eg, fresh allograft) may provide satisfactory outcomes after a failed
attempt at surgical management. Irrespective of the surgical technique used,
outcomes are generally worse in the patellofemoral compartment than in the
tibiofemoral joint. The concomitant management of associated pathology, including
patellar malalignment, is recommended because it has been shown to improve the
success of cartilage restoration procedures.
PMID- 28406877
TI - Scapulothoracic Dissociation: Evaluation and Management.
AB - Scapulothoracic dissociation is a rare, potentially limb- and life-threatening
injury of the shoulder girdle. The injury is characterized by lateral
displacement of the scapula resulting from traumatic disruption of the
scapulothoracic articulation. The typical physical examination findings consist
of substantial swelling of the shoulder girdle, along with weakness, numbness,
and pulselessness in the ipsilateral upper extremity. Radiographic evaluation
includes measurement of the scapular index on a nonrotated chest radiograph and
assessment for either a distracted clavicle fracture or a disrupted
acromioclavicular or sternoclavicular joint. Although vascular injury occurs in
most patients, emergent surgery is performed only in patients with either limb
threatening ischemia or active arterial hemorrhage. Management of neurologic
injury can be delayed if necessary. The location and severity of neurologic
injury determine whether observation, nerve grafting, nerve transfer, or above
elbow amputation is performed. Skeletal stabilization procedures include plate
fixation of clavicle fractures and reduction of distracted acromioclavicular or
sternoclavicular joints. The extent of neurologic injury determines clinical
outcomes. Medical Outcomes Study 36-Item Short Form scores are significantly
lower in patients with complete brachial plexus avulsion injury than in patients
with postganglionic injury.
PMID- 28406878
TI - Bone Loss in Revision Total Knee Arthroplasty: Evaluation and Management.
AB - With the increasing number of total knee arthroplasty (TKA) procedures being
performed annually, the burden of revision surgery is also expected to increase.
Addressing bone loss during revision TKA is a considerable challenge that
requires proper preoperative evaluation and surgical planning. In addition to an
assessment of femoral and tibial bone loss, a systematic approach to the
management of bone loss associated with TKA includes careful implant selection,
adherence to the general principles of revision TKA, and an understanding of the
available reconstruction options. These options include cement with screws,
morcellized allograft, bulk structural allograft, modular wedges, block augments,
porous metal cones or sleeves, and megaprostheses.
PMID- 28406879
TI - Physical Examination of the Knee: Meniscus, Cartilage, and Patellofemoral
Conditions.
AB - The knee is one of the most commonly injured joints in the body. Its superficial
anatomy enables diagnosis of the injury through a thorough history and physical
examination. Examination techniques for the knee described decades ago are still
useful, as are more recently developed tests. Proper use of these techniques
requires understanding of the anatomy and biomechanical principles of the knee as
well as the pathophysiology of the injuries, including tears to the menisci and
extensor mechanism, patellofemoral conditions, and osteochondritis dissecans.
Nevertheless, the clinical validity and accuracy of the diagnostic tests vary.
Advanced imaging studies may be useful adjuncts.
PMID- 28406880
TI - AAOS Appropriate Use Criteria: Treatment of Hip Fractures in the Elderly.
PMID- 28406881
TI - Early Healing Evaluation of Commercially Pure Titanium and Ti-6Al-4V Presenting
Similar Surface Texture: An In Vivo Study.
AB - OBJECTIVE: This study evaluated the osseointegration of commercially pure
titanium (Ti) grade-2 (G2) and Ti-6Al-4V alloy (G5) implants with the same
geometry and surface treatment. MATERIALS AND METHODS: Thirty-six dental implants
with a grit-blasted acid-etched surface were used (n = 18, each). Two implants,
one per group, were installed in each subject, in the radius diaphysis (n = 18
beagle dogs), with interchanged fixture position (proximal-distal) between
animals for a balanced number of devices per group and time in vivo (1, 3, and 6
weeks). RESULTS: Similar topographical parameters between G2 and G5 were observed
for average surface roughness, root mean square, developed surface ratio, maximum
height of surface, and density of summits. Removal torque was significantly
higher for G5 than for G2. No differences were observed for bone-to-implant
contact and bone-area-fraction occupancy. Removal torque significantly increased
with time for both groups. At 1 week, new bone formation in direct contact with
the implant surface and osteogenic tissue migration was observed with an increase
in woven bone formation at 3 weeks followed by the onset of lamellar bone
formation at 6 weeks. CONCLUSION: Although both surfaces were biocompatible and
osteoconductive, increased removal torque was observed for Ti-6Al-4V compared
with commercially pure Ti implants.
PMID- 28406882
TI - Impact of Patient Education on Compliance with Positive Airway Pressure Treatment
in Obstructive Sleep Apnea.
AB - BACKGROUND We addressed the impact of patient education followed by frequent
visits on compliance with positive airway pressure (PAP) treatment in patients
with obstructive sleep apnea (OSA) in a Turkish sleep clinic cohort. MATERIAL AND
METHODS This single-center, randomized, controlled study was conducted in
Istanbul, Turkey between June 2014 and April 2015. Among 115 eligible OSA
patients (mean age 51.0+/-9.3 years; 75.5% men), 63 were randomized to standard
support (SS) group (general information about OSA and PAP treatment at baseline),
and 52 to educational support (ES) group (additional polysomnography chart
viewing from both diagnostic and titration nights). All patients were scheduled
to five PAP control visits between two weeks and six months after the PAP
prescription. Primary outcome was the PAP compliance (4 hours/night for 70% of
all the nights) at the last visit. RESULTS Average PAP usage was 4.2+/-2.5
hours/night in the SS group, and 5.2+/-2.1 hours/night in the ES group (p=0.027).
PAP compliance was achieved among 68.3% in the SS group, and 86.5% in the ES
group (p=0.021). In a multivariate analysis, ES strategy followed by frequent
visits predicted PAP compliance (odds ratio [OR] 3.6, 95% confidence interval
[CI] 1.2-10.6; p=0.020). Other predictors were obesity (OR 3.4, 95% CI 1.2-9.7;
p=0.019) and severe OSA (apnea-hypopnea index >=30/hour) at baseline (OR 4.7, 95%
CI 1.2-17.6; p=0.023). Primary school education level was inversely related with
PAP compliance (OR 0.3, 95% CI 0.1-0.9; p=0.036). CONCLUSIONS Patient education
with polysomnography chart view followed by frequent visits increased long-term
compliance with PAP treatment.
PMID- 28406883
TI - Characteristics of Fentanyl Overdose - Massachusetts, 2014-2016.
AB - Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The
proportion of opioid overdose deaths in the state involving fentanyl, a
synthetic, short-acting opioid with 50-100 times the potency of morphine,
increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In
April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law
enforcement fentanyl seizures in Massachusetts, much of which was believed to be
illicitly manufactured fentanyl (IMF) (4). To guide overdose prevention and
response activities, in April 2016, the Massachusetts Department of Public Health
and the Office of the Chief Medical Examiner collaborated with CDC to investigate
the characteristics of fentanyl overdose in three Massachusetts counties with
high opioid overdose death rates. In these counties, medical examiner charts of
opioid overdose decedents who died during October 1, 2014-March 31, 2015 were
reviewed, and during April 2016, interviews were conducted with persons who used
illicit opioids and witnessed or experienced an opioid overdose. Approximately
two thirds of opioid overdose decedents tested positive for fentanyl on
postmortem toxicology. Evidence for rapid progression of fentanyl overdose was
common among both fatal and nonfatal overdoses. A majority of interview
respondents reported successfully using multiple doses of naloxone, the antidote
to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and
enhancing existing opioid overdose education and prevention programs to include
fentanyl-specific messaging and practices could help public health authorities
mitigate adverse effects associated with overdoses, especially in communities
affected by IMF.
PMID- 28406884
TI - Use of Video Directly Observed Therapy for Treatment of Latent Tuberculosis
Infection - Johnson County, Kansas, 2015.
AB - Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis and is
spread from person to person through the air. TB can be spread in congregate
settings, such as school environments, to varying degrees, based on factors
including duration of contact and air ventilation (1); therefore, evaluating
potential contacts and exposures can be challenging. In February 2015, a student
at a Kansas high school received a diagnosis of active pulmonary TB disease.
Screening of 385 (91%) school contacts, four (100%) household contacts, and 19
(90%) social contacts resulted in the identification of 50 persons with latent TB
infection. Johnson County Department of Health and Environment (JCDHE) Public
Health Emergency Preparedness personnel used their experience with points of
distribution logistics to optimize testing clinic layouts and implement the
incident command structure. Open communication with students, school staff
members, the public, and the media about the investigation from the outset was
imperative to reduce rumors and unease that can accompany a large communicable
disease investigation. The large number of persons needing treatment for latent
TB overwhelmed JCDHE's two TB nurses. As a result, JCDHE developed a policy and
procedure to allow persons who met eligibility requirements to complete 12 weekly
doses of isoniazid and rifapentine treatment using video directly observed
therapy (VDOT) rather than traditional in-person directly observed therapy (DOT).
This procedure facilitated treatment compliance and completion; among the
eligible 15 persons who chose the 12-week VDOT option, 14 (93%) completed
treatment. State and local health departments might consider use of VDOT to
monitor treatment of persons with latent TB infection.
PMID- 28406885
TI - QuickStats: Percentage Distribution of Gestational Age in Weeks for Infants Who
Survived to Age 1 Year and Infants Who Died Before Age 1 Year - National Vital
Statistics System, United States, 2014.
AB - Infants who do not survive the first year of life are more likely to be born at
earlier gestational ages. In 2014, 66% of infants who survived to age 1 year were
delivered at full term or later (>=39 completed weeks) compared with 16% of
infants who died before reaching age 1 year. Fifty-eight percent of infants who
died before age 1 year were delivered at <32 weeks gestation compared with only
1% of infants who survived to age 1 year.
PMID- 28406886
TI - Notes from the Field: Complications of Mumps During a University Outbreak Among
Students Who Had Received 2 Doses of Measles-Mumps-Rubella Vaccine - Iowa, July
2015-May 2016.
PMID- 28406887
TI - Hospitalizations for Crohn's Disease - United States, 2003-2013.
AB - In 2009, an estimated 565,000 Americans had Crohn's disease (1), an inflammatory
bowel disorder that can affect any part of the gastrointestinal tract. Symptoms
include persistent diarrhea, abdominal cramps and pain, constipation leading to
bowel obstruction, and rectal bleeding.* Symptoms sometimes intensify in severity
and require hospitalization and surgeries of the small intestine, colon, or
rectum (2). Hospital discharge data from the National Inpatient Sample (NIS) of
the Healthcare Cost and Utilization Project (HCUP) were used to estimate U.S.
hospitalizations? for Crohn's disease as both the first-listed and any-listedS
discharge diagnosis and common surgical procedures during hospitalizations with
Crohn's disease as first-listed diagnosis from 2003 to 2013, the most recent
decade of data. Despite new therapies that were expected to improve remission and
reduce hospitalizations, estimated numbers (and age-adjusted rates per 100,000
U.S. population) of hospitalizations for Crohn's disease as the first-listed
diagnosis did not change significantly from 2003 to 2013. The proportion of these
hospitalizations during which small bowel resection was performed decreased from
4.9% in 2003 to 3.9% in 2013 (p<0.05); however, colorectal resection and fistula
repair rates remained stable. Hospital stays for any-listed Crohn's disease
increased from >120,000 (44.2 per 100,000) in 2003 to >196,000 (59.7 per 100,000)
in 2013 (p<0.05). Patient education initiatives should focus on increasing
awareness of exacerbating factors and medication compliance to prevent
hospitalizations.
PMID- 28406888
TI - Targeted protein degradation: You can glue it too!
PMID- 28406890
TI - Microbiology: A new language for small talk.
PMID- 28406893
TI - The chemical basis for electrical signaling.
AB - Electrical signals generated by minute currents of ions moving across cell
membranes are central to all rapid processes in biology. Initiation and
propagation of electrical signals requires voltage-gated sodium (NaV) and calcium
(CaV) channels. These channels contain a tetramer of membrane-bound subunits or
domains comprising a voltage sensor and a pore module. Voltage-dependent
activation occurs as membrane depolarization drives outward movements of positive
gating changes in the voltage sensor via a sliding-helix mechanism, which leads
to a conformational change in the pore module that opens its intracellular
activation gate. A unique negatively charged site in the selectivity filter
conducts hydrated Na+ or Ca2+ rapidly and selectively. Ion conductance is
terminated by voltage-dependent inactivation, which causes asymmetric pore
collapse. This Review focuses on recent advances in structure and function of NaV
and CaV channels that expand our current understanding of the chemical basis for
electrical signaling mechanisms conserved from bacteria to humans.
PMID- 28406895
TI - The superfamily keeps growing: Identification in trypanosomatids of RibJ, the
first riboflavin transporter family in protists.
AB - BACKGROUND: Trypanosomatid parasites represent a major health issue affecting
hundreds of million people worldwide, with clinical treatments that are partially
effective and/or very toxic. They are responsible for serious human and plant
diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei
(Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp.
(phytoparasites). Both, animals and trypanosomatids lack the biosynthetic
riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide
(FMN) and flavin adenine dinucleotide (FAD) cofactors. While metazoans obtain
riboflavin from the diet through RFVT/SLC52 transporters, the riboflavin
transport mechanisms in trypanosomatids still remain unknown.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that riboflavin is imported with
high affinity in Trypanosoma cruzi, Trypanosoma brucei, Leishmania (Leishmania)
mexicana, Crithidia fasciculata and Phytomonas Jma using radiolabeled riboflavin
transport assays. The vitamin is incorporated through a saturable carrier
mediated process. Effective competitive uptake occurs with riboflavin analogs
roseoflavin, lumiflavin and lumichrome, and co-factor derivatives FMN and FAD.
Moreover, important biological processes evaluated in T. cruzi (i.e.
proliferation, metacyclogenesis and amastigote replication) are dependent on
riboflavin availability. In addition, the riboflavin competitive analogs were
found to interfere with parasite physiology on riboflavin-dependent processes. By
means of bioinformatics analyses we identified a novel family of riboflavin
transporters (RibJ) in trypanosomatids. Two RibJ members, TcRibJ and TbRibJ from
T. cruzi and T. brucei respectively, were functionally characterized using
homologous and/or heterologous expression systems. CONCLUSIONS/SIGNIFICANCE: The
RibJ family represents the first riboflavin transporters found in protists and
the third eukaryotic family known to date. The essentiality of riboflavin for
trypanosomatids, and the structural/biochemical differences that RFVT/SLC52 and
RibJ present, make the riboflavin transporter -and its downstream metabolism- a
potential trypanocidal drug target.
PMID- 28406896
TI - Inferring modulators of genetic interactions with epistatic nested effects
models.
AB - Maps of genetic interactions can dissect functional redundancies in cellular
networks. Gene expression profiles as high-dimensional molecular readouts of
combinatorial perturbations provide a detailed view of genetic interactions, but
can be hard to interpret if different gene sets respond in different ways (called
mixed epistasis). Here we test the hypothesis that mixed epistasis between a gene
pair can be explained by the action of a third gene that modulates the
interaction. We have extended the framework of Nested Effects Models (NEMs), a
type of graphical model specifically tailored to analyze high-dimensional gene
perturbation data, to incorporate logical functions that describe interactions
between regulators on downstream genes and proteins. We benchmark our approach in
the controlled setting of a simulation study and show high accuracy in inferring
the correct model. In an application to data from deletion mutants of kinases and
phosphatases in S. cerevisiae we show that epistatic NEMs can point to modulators
of genetic interactions. Our approach is implemented in the R-package 'epiNEM'
available from https://github.com/cbg-ethz/epiNEM and
https://bioconductor.org/packages/epiNEM/.
PMID- 28406897
TI - Changes in the living arrangement and risk of stroke in Japan; does it matter who
lives in the household? Who among the family matters?
AB - Previous studies have suggested associations of family composition with morbidity
and mortality; however, the evidence of associations with risk of stroke is
limited. We sought to examine the impact of changes in the household composition
on risk of stroke and its types in Japanese population. Cox proportional hazard
modelling was used to assess the risk of incident stroke and stroke types within
a cohort of 77,001 Japanese men and women aged 45-74 years who experienced
addition and/or loss of family members [spouse, child(ren), parent(s) and others]
to their households over a five years interval (between 1990-1993 and 1995-1998).
During 1,043,446 person-years of the follow-up for 35,247 men and 41,758 women, a
total of 3,858 cases of incident stroke (1485 hemorrhagic and 2373 ischemic) were
documented. When compared with a stable family composition, losing at least one
family member was associated with 11-15% increased risk of stroke in women and
men; hazard ratios (95% confidence interval) were 1.11 (1.01-1.22) and 1.15 (1.05
1.26), respectively. The increased risk was associated with the loss of a spouse,
and was evident for ischemic stroke in men and hemorrhagic stroke in women. The
addition of any family members to the household was not associated with risk of
stroke in men, whereas the addition of a parent (s) to the household was
associated with increased risk in women: 1.49 (1.09-2.28). When the loss of a
spouse was accompanied by the addition of other family members to the household,
the increased risk of stroke disappeared in men: 1.18 (0.85-1.63), but
exacerbated in women: 1.58 (1.19-2.10). In conclusion, men who have lost family
members, specifically a spouse have higher risk of ischemic stroke, and women who
gained family members; specifically a parent (s) had the higher risk of
hemorrhagic stroke than those with a stable family composition.
PMID- 28406898
TI - Spatial relationship between Taenia solium tapeworm carriers and necropsy cyst
burden in pigs.
AB - BACKGROUND: Taenia solium, a parasite that affects humans and pigs, is the
leading cause of preventable epilepsy in the developing world. Geographic
hotspots of pigs testing positive for serologic markers of T. solium exposure
have been observed surrounding the locations of human tapeworm carriers. This
clustered pattern of seropositivity in endemic areas formed the basis for
geographically targeted control interventions, which have been effective at
reducing transmission. In this study, we further explore the spatial relationship
between human tapeworm carriers and infected pigs using necroscopic examination
as a quantitative gold-standard diagnostic to detect viable T. solium cyst
infection in pigs. METHODOLOGY/PRINCIPAL FINDINGS: We performed necroscopic
examinations on pigs from 7 villages in northern Peru to determine the number of
viable T. solium cysts in each pig. Participating humans in the study villages
were tested for T. solium tapeworm infection (i.e., taeniasis) with an ELISA
coproantigen assay, and the distances from each pig to its nearest human tapeworm
carrier were calculated. We assessed the relationship between proximity to a
tapeworm carrier and the prevalence of light, moderate, and heavy cyst burden in
pigs. The prevalence of pig infection was greatest within 50 meters of a tapeworm
carrier and decreased monotonically as distance increased. Pigs living less than
50 meters from a human tapeworm carrier were 4.6 times more likely to be infected
with at least one cyst than more distant pigs. Heavier cyst burdens, however,
were not more strongly associated with proximity to tapeworm carriers than light
cyst burdens. CONCLUSION/SIGNIFICANCE: Our study shows that human tapeworm
carriers and pigs with viable T. solium cyst infection are geographically
correlated in endemic areas. This finding supports control strategies that treat
humans and pigs based on their proximity to other infected individuals. We did
not, however, find sufficient evidence that heavier cyst burdens in pigs would
serve as improved targets for geographically focused control interventions.
PMID- 28406899
TI - Histone deacetylase inhibition modulates histone acetylation at gene promoter
regions and affects genome-wide gene transcription in Schistosoma mansoni.
AB - BACKGROUND: Schistosomiasis is a parasitic disease infecting hundreds of millions
of people worldwide. Treatment depends on a single drug, praziquantel, which
kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors
(HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro
(schistosomula and adult worms), however the downstream effects of histone
hyperacetylation on the parasite are not known. METHODOLOGY/PRINCIPAL FINDINGS:
TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and
H3K14ac, which are transcription activation marks, not affecting the unrelated
transcription repression mark H3K27me3. We investigated the effect of TSA HDACi
on schistosomula gene expression at three different time points, finding a marked
genome-wide change in the transcriptome profile. Gene transcription activity was
correlated with changes on the chromatin acetylation mark at gene promoter
regions. Moreover, combining expression data with ChIP-Seq public data for
schistosomula, we found that differentially expressed genes having the H3K4me3
mark at their promoter region in general showed transcription activation upon
HDACi treatment, compared with those without the mark, which showed transcription
down-regulation. Affected genes are enriched for DNA replication processes, most
of them being up-regulated. Twenty out of 22 genes encoding proteins involved in
reducing reactive oxygen species accumulation were down-regulated. Dozens of
genes encoding proteins with histone reader motifs were changed, including SmEED
from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a
new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA,
significantly increasing schistosomula mortality. CONCLUSIONS/SIGNIFICANCE:
Genome-wide gene expression analyses have identified important pathways and
cellular functions that were affected and may explain the schistosomicidal effect
of TSA HDACi. The change in expression of dozens of histone reader genes involved
in regulation of the epigenetic program in S. mansoni can be used as a starting
point to look for possible novel schistosomicidal targets.
PMID- 28406901
TI - Automatic extraction of endocranial surfaces from CT images of crania.
AB - The authors present a method for extracting polygon data of endocranial surfaces
from CT images of human crania. Based on the fact that the endocast is the
largest empty space in the crania, we automate a procedure for endocast
extraction by integrating several image processing techniques. Given CT images of
human crania, the proposed method extracts endocranial surfaces by the following
three steps. The first step is binarization in order to fill void structures,
such as diploic space and cracks in the skull. We use a void detection method
based on mathematical morphology. The second step is watershed-based segmentation
of the endocranial part from the binary image of the CT image. Here, we introduce
an automatic initial seed assignment method for the endocranial region using the
distance field of the binary image. The final step is partial polygonization of
the CT images using the segmentation results as mask images. The resulting
polygons represent only the endocranial part, and the closed manifold surfaces
are computed even though the endocast is not isolated in the cranium. Since only
the isovalue threshold and the size of void structures are required, the
procedure is not dependent on the experience of the user. The present paper also
demonstrates that the proposed method can extract polygon data of endocasts from
CT images of various crania.
PMID- 28406902
TI - Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic
kidney disease-like phenotypes in Drosophila.
AB - Progressive cystic kidney degeneration underlies diverse renal diseases,
including the most common cause of kidney failure, autosomal dominant Polycystic
Kidney Disease (PKD). Genetic analyses of patients and animal models have
identified several key drivers of this disease. The precise molecular and
cellular changes underlying cystogenesis remain, however, elusive. Drosophila
mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of
vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic
degeneration of the renal tubules (so called "Malpighian" tubules) and reduced
renal function. The BicC protein was shown to bind to Drosophila (d-) myc mRNA in
tubules. Elevation of d-Myc protein levels was a cause of tubular degeneration in
BicC mutants. Activation of the Target of Rapamycin (TOR) kinase pathway, another
common feature of PKD, was found in BicC mutant flies. Rapamycin administration
substantially reduced the cystic phenotype in flies. We present new mechanistic
insight on BicC function and propose that Drosophila may serve as a genetically
tractable model for dissecting the evolutionarily-conserved molecular mechanisms
of renal cystogenesis.
PMID- 28406900
TI - Gene co-expression network connectivity is an important determinant of selective
constraint.
AB - While several studies have investigated general properties of the genetic
architecture of natural variation in gene expression, few of these have
considered natural, outbreeding populations. In parallel, systems biology has
established that a general feature of biological networks is that they are scale
free, rendering them buffered against random mutations. To date, few studies have
attempted to examine the relationship between the selective processes acting to
maintain natural variation of gene expression and the associated co-expression
network structure. Here we utilised RNA-Sequencing to assay gene expression in
winter buds undergoing bud flush in a natural population of Populus tremula, an
outbreeding forest tree species. We performed expression Quantitative Trait Locus
(eQTL) mapping and identified 164,290 significant eQTLs associating 6,241 unique
genes (eGenes) with 147,419 unique SNPs (eSNPs). We found approximately four
times as many local as distant eQTLs, with local eQTLs having significantly
higher effect sizes. eQTLs were primarily located in regulatory regions of genes
(UTRs or flanking regions), regardless of whether they were local or distant. We
used the gene expression data to infer a co-expression network and investigated
the relationship between network topology, the genetic architecture of gene
expression and signatures of selection. Within the co-expression network, eGenes
were underrepresented in network module cores (hubs) and overrepresented in the
periphery of the network, with a negative correlation between eQTL effect size
and network connectivity. We additionally found that module core genes have
experienced stronger selective constraint on coding and non-coding sequence, with
connectivity associated with signatures of selection. Our integrated genetics and
genomics results suggest that purifying selection is the primary mechanism
underlying the genetic architecture of natural variation in gene expression
assayed in flushing leaf buds of P. tremula and that connectivity within the co
expression network is linked to the strength of purifying selection.
PMID- 28406903
TI - From elementary flux modes to elementary flux vectors: Metabolic pathway analysis
with arbitrary linear flux constraints.
AB - Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic
pathways and have become an established tool for constraint-based modeling and
metabolic network analysis. EFMs are characteristic (support-minimal) vectors of
the flux cone that contains all feasible steady-state flux vectors of a given
metabolic network. EFMs account for (homogeneous) linear constraints arising from
reaction irreversibilities and the assumption of steady state; however, other
(inhomogeneous) linear constraints, such as minimal and maximal reaction rates
frequently used by other constraint-based techniques (such as flux balance
analysis [FBA]), cannot be directly integrated. These additional constraints
further restrict the space of feasible flux vectors and turn the flux cone into a
general flux polyhedron in which the concept of EFMs is not directly applicable
anymore. For this reason, there has been a conceptual gap between EFM-based
(pathway) analysis methods and linear optimization (FBA) techniques, as they
operate on different geometric objects. One approach to overcome these
limitations was proposed ten years ago and is based on the concept of elementary
flux vectors (EFVs). Only recently has the community started to recognize the
potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent
the conceptual development required to generalize the idea of EFMs from flux
cones to flux polyhedra. This work aims to present a concise theoretical and
practical introduction to EFVs that is accessible to a broad audience. We
highlight the close relationship between EFMs and EFVs and demonstrate that
almost all applications of EFMs (in flux cones) are possible for EFVs (in flux
polyhedra) as well. In fact, certain properties can only be studied with EFVs.
Thus, we conclude that EFVs provide a powerful and unifying framework for
constraint-based modeling of metabolic networks.
PMID- 28406904
TI - Relationship between bone turnover and left ventricular function in primary
hyperparathyroidism: The EPATH trial.
AB - Observational studies suggested a link between bone disease and left ventricular
(LV) dysfunction that may be pronounced in hyperparathyroid conditions. We
therefore aimed to test the hypothesis that circulating markers of bone turnover
correlate with LV function in a cohort of patients with primary
hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were
analyzed who participated in the "Eplerenone in Primary Hyperparathyroidism"
(EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction
(LVEF, systolic function) or peak early transmitral filling velocity (e',
diastolic function) as dependent variables and N-terminal propeptide of
procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase
(BALP), or beta-crosslaps (CTX) as the respective independent variable were
performed. Analyses were additionally adjusted for plasma parathyroid hormone,
plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood
pressure, smoking status, estimated glomerular filtration rate, antihypertensive
treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain
B-type natriuretic peptide. Independent relationships were observed between P1NP
and LVEF (adjusted beta-coefficient = 0.201, P = 0.035) and e' (beta = 0.188, P =
0.042), respectively. OC (beta = 0.192, P = 0.039) and BALP (beta = 0.198, P =
0.030) were each independently related with e'. CTX showed no correlations with
LVEF or e'. In conclusion, high bone formation markers were independently and
paradoxically related with better LV diastolic and, partly, better systolic
function, in the setting of pHPT. Potentially cardio-protective properties of
stimulated bone formation in the context of hyperparathyroidism should be
explored in future studies.
PMID- 28406905
TI - A latitudinal phylogeographic diversity gradient in birds.
AB - High tropical species diversity is often attributed to evolutionary dynamics over
long timescales. It is possible, however, that latitudinal variation in
diversification begins when divergence occurs within species. Phylogeographic
data capture this initial stage of diversification in which populations become
geographically isolated and begin to differentiate genetically. There is limited
understanding of the broader implications of intraspecific diversification
because comparative analyses have focused on species inhabiting and evolving in
restricted regions and environments. Here, we scale comparative phylogeography up
to the hemisphere level and examine whether the processes driving latitudinal
differences in species diversity are also evident within species. We collected
genetic data for 210 New World bird species distributed across a broad
latitudinal gradient and estimated a suite of metrics characterizing
phylogeographic history. We found that lower latitude species had, on average,
greater phylogeographic diversity than higher latitude species and that
intraspecific diversity showed evidence of greater persistence in the tropics.
Factors associated with species ecologies, life histories, and habitats explained
little of the variation in phylogeographic structure across the latitudinal
gradient. Our results suggest that the latitudinal gradient in species richness
originates, at least partly, from population-level processes within species and
are consistent with hypotheses implicating age and environmental stability in the
formation of diversity gradients. Comparative phylogeographic analyses scaled up
to large geographic regions and hundreds of species can show connections between
population-level processes and broad-scale species-richness patterns.
PMID- 28406908
TI - Considering land tenure in REDD+ participatory measurement, reporting, and
verification: A case study from Indonesia.
AB - Measurement, Reporting, and Verification (MRV) systems are thought to be
essential for effective carbon accounting and joint REDD+ carbon, conservation,
and social development goals. Community participation in MRV (PMRV) has been
shown to be both cost effective and accurate, as well as a method to potentially
advance stakeholder empowerment and perceptions of legitimacy. Recognizing land
tenure as a long-standing point of tension in REDD+ planning, we argue that its
engagement also has a key role to play in developing a legitimate PMRV. Using
household surveys, key informant interviews, and participatory mapping exercises,
we present three 'lived' land tenure contexts in Indonesia to highlight their
socially and ecologically situated natures and to consider the role of tenure
pluralism in shaping PMRV. We then raise and interrogate three questions for
incorporating lived land tenure contexts into a legitimate PMRV system: 1) Who
holds the right to conduct PMRV activities?; 2) How are the impacts of PMRV
differentially distributed within local communities?; and 3) What is the
relationship between tenure security and motivation to participate in PMRV? We
conclude with implementation lessons for REDD+ practitioners, including the
benefits of collaborative practices, and point to critical areas for further
research.
PMID- 28406906
TI - Water diffusion closely reveals neural activity status in rat brain loci affected
by anesthesia.
AB - Diffusion functional MRI (DfMRI) reveals neuronal activation even when
neurovascular coupling is abolished, contrary to blood oxygenation level
dependent (BOLD) functional MRI (fMRI). Here, we show that the water apparent
diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain
regions under anesthetic conditions, reflecting the decreased neuronal activity
observed with local field potentials (LFPs), especially in regions involved in
wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting
systemic effects of the anesthesia on overall brain hemodynamics status.
Electrical stimulation of the central medial thalamus nucleus (CM) exhibiting
this anesthesia-induced ADC increase led the animals to transiently wake up.
Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the
ADC to increase further locally, although LFP activity remained unchanged, and
increased the current threshold awakening the animals under CM electrical
stimulation. Oppositely, induction of cell swelling in the CM through infusion of
a hypotonic solution (-80 milliosmole [mOsm] artificial cerebrospinal fluid
[aCSF]) led to a local ADC decrease and a lower current threshold to wake up the
animals. Strikingly, the local ADC changes produced by blocking or enhancing cell
swelling in the CM were also mirrored remotely in areas functionally connected to
the CM, such as the cingulate and somatosensory cortex. Together, those results
strongly suggest that neuronal swelling is a significant mechanism underlying
DfMRI.
PMID- 28406907
TI - Painless swelling of the forefoot and recurrent subcutaneous abscesses of the
lower leg-Two distinct presentations illustrating the spectrum of eumycetoma in a
nonendemic country.
PMID- 28406909
TI - Sustained effectiveness of weekly iron-folic acid supplementation and regular
deworming over 6 years in women in rural Vietnam.
AB - BACKGROUND: Weekly iron-folic acid (IFA) supplementation and regular deworming is
effective for the prevention of iron deficiency and anaemia in women of child
bearing age. Between 2006 and 2013, a program of weekly IFA and biannual
deworming was implemented in Yen Bai province, Vietnam. In this study we aimed to
determine the effectiveness of the program in reducing anaemia and the prevalence
of hookworm infection after 72 months (six years). METHODS: This prospective
cohort study followed up a cohort of 389 women of child-bearing age from baseline
until six years after the introduction of the weekly IFA (one tablet containing
200 mg ferrous sulphate, 0.4mg folic acid) and deworming (one 400mg tablet of
albendazole given twice yearly) program (May 2006 to 2012). In each of the six
surveys (baseline and five follow-up surveys) we measured haemoglobin and
ferritin, and the burden of soil transmitted helminth (STH) infections, and in
the 72 month survey we also administered a questionnaire to assess adherence and
possible impediments to participating in the program. RESULTS: Two hundred and
fifty six (65.8%) of the original 389 women enrolled in the cohort attended the
final 72 month survey. Haemoglobin levels were 122 g/L [95% C.I. 120, 124] at
baseline and increased to 135g/L [95% C.I. 133, 138] after 72 months. The
prevalence of anaemia was 37.8% [95% C.I. 31.0, 44.7] at baseline and reduced to
14.3% [95% C.I. 9.5, 19.1]. Hookworm infection prevalence, 75.9% [95% C.I. 68.1,
83.8] at baseline, reduced to 10.2% [95% C.I. 5.4, 15.0] with no moderate or
heavy intensity infections. Seventy-two percent of participants reported still
taking at least 75% of the weekly supplements, and 85.0% had taken the most
recent deworming treatment. DISCUSSION: Anaemia rates fell significantly during
the six-year program, and STH infections were eliminated as a public health risk.
Adherence was well maintained but long-term sustainability is challenging in the
absence of ongoing external support.
PMID- 28406911
TI - Phylogenetic analysis of family Neisseriaceae based on genome sequences and
description of Populibacter corticis gen. nov., sp. nov., a member of the family
Neisseriaceae, isolated from symptomatic bark of Populus * euramericana canker.
AB - Two Gram-stain negative aerobic bacterial strains were isolated from the bark
tissue of Populus * euramericana. The novel isolates were investigated using a
polyphasic approach including 16S rRNA gene sequencing, genome sequencing,
average nucleotide identity (ANI) and both phenotypic and chemotaxonomic assays.
The genome core gene sequence and 16S rRNA gene phylogenies suggest that the
novel isolates are different from the genera Snodgrassella and Stenoxybacter.
Additionally, the ANI, G+C content, main fatty acids and phospholipid profile
data supported the distinctiveness of the novel strain from genus Snodgrassella.
Therefore, based on the data presented, the strains constitute a novel species of
a novel genus within the family Neisseriaceae, for which the name Populibacter
corticis gen. nov., sp. nov. is proposed. The type strain is 15-3-5T (= CFCC
13594T = KCTC 42251T).
PMID- 28406910
TI - Nutrient enrichment is associated with altered nectar and pollen chemical
composition in Succisa pratensis Moench and increased larval mortality of its
pollinator Bombus terrestris L.
AB - Pollinators are declining worldwide and possible underlying causes include
disease, invasive pest species and large scale land use changes resulting in
habitat loss and degradation. One particular cause of habitat degradation is the
increased inflow of nutrients due to anthropogenic combustion processes and large
scale application of agricultural fertilizers. This nutrient pollution has been
shown to affect pollinators through the loss of nectar and pollen-providing plant
species. However, it may also affect pollinators through altering the nectar and
pollen chemical composition of plant species, hence influencing pollinator food
quality. Here, we experimentally investigated the effect of nutrient enrichment
on amino acid and sugar composition of nectar and pollen in the grassland plant
Sucissa pratensis, and the subsequent colony size and larval mortality of the
pollinating bumblebee Bombus terrestris. We found less of the essential amino
acids glycine and arginine in the pollen of fertilized plants, and more arginine,
ornithine and threonine in the pollen of control plants. Nectar glucose and
pollen fructose levels were lower in fertilized plants as compared to control
plants. Furthermore, bumblebee colonies visiting fertilized plants showed more
dead larvae than colonies visiting control plants. Our results suggest that the
fitness of bumblebees can be negatively affected by changes in their food quality
following nutrient pollution. If similar patterns hold for other plant and
pollinator species, this may have far reaching implications for the maintenance
of pollination ecosystem services, as nutrient pollution continues to rise
worldwide.
PMID- 28406912
TI - The elusive MAESTRO gene: Its human reproductive tissue-specific expression
pattern.
AB - The encoded transcript of the Maestro-Male-specific Transcription in the
developing Reproductive Organs (MRO) gene exhibits sexual dimorphic expression
during murine gonadal development. The gene has no homology to any known gene and
its expression pattern, protein function or structure are still unknown.
Previously, studying gene expression in human ovarian cumulus cells, we found
increased expression of MRO in lean-type Polycystic Ovarian Syndrome (PCOS)
subjects, as compared to controls. In this study, we examined the MRO splice
variants and protein expression pattern in various human tissues and cells. We
found a differential expression pattern of the MRO 5'-UTR region in luteinized
granulosa-cumulus cells and in testicular tissues as compared to non-gonadal
tissues. Our study also shows a punctate nuclear expression pattern and disperse
cytoplasmic expression pattern of the MRO protein in human granulosa-cumulus
cells and in testicular germ cells, which was later validated by western
blotting. The tentative and unique features of the protein hampered our efforts
to gain more insight about this elusive protein. A better understanding of the
tissue-specific MRO isoforms expression patterns and the unique structure of the
protein may provide important insights into the function of this gene and
possibly to the pathophysiology of PCOS.
PMID- 28406913
TI - No age effect in the prevalence and clinical significance of ultra-high risk
symptoms and criteria for psychosis in 22q11 deletion syndrome: Confirmation of
the genetically driven risk for psychosis?
AB - BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is one of the highest known
risk factors for schizophrenia. Thus, the detection of 22q11DS patients at
particularly high risk of psychosis is important, yet studies on the clinical
significance of the widely used ultra-high risk (UHR) criteria in 22q11DS are
inconclusive. Since age was reported to moderate clinical significance of UHR
symptoms in community samples, we explored whether age at presentation of UHR
symptoms and criteria may explain part of this heterogeneity. METHODS: 111
patients with 22q11DS (8-30 years; 15.7+/-4.7) were assessed for UHR
symptoms/criteria. Information on diagnoses, psychosocial functioning, and IQ
were collected. RESULTS: Any UHR symptom was reported by 38.7%, any UHR criterion
by 27%. No significant influence of age on the prevalence of UHR symptoms or
criteria was detected. Moreover, age did not significantly modulate the
association between UHR symptoms and functioning. However, significant
interaction terms suggested that younger age groups were more likely to meet UHR
criteria in the presence of UHR symptoms compared to the adult group. DISCUSSION:
Compared to the general population, prevalence of UHR symptoms and criteria was
3.8-fold and 20.8-fold in our 22q11DS sample. Contrary to the general population,
age only modulated the prevalence of UHR criteria among those with UHR symptoms,
but not their prevalence per se or their clinical significance. This suggests
that UHR symptoms might develop as a trait factor in terms of a genetically
driven schizotypal disposition in 22q11DS, thus necessitating future studies on
psychosis-risk indicators in this genetic high-risk group.
PMID- 28406914
TI - The marker choice: Unexpected resolving power of an unexplored CO1 region for
layered DNA barcoding approaches.
AB - The potential of DNA barcoding approaches to identify single species and
characterize species compositions strongly depends on the marker choice. The
prominent "Folmer region", a 648 basepair fragment at the 5' end of the
mitochondrial CO1 gene, has been traditionally applied as a universal DNA
barcoding region for metazoans. In order to find a suitable marker for
biomonitoring odonates (dragonflies and damselflies), we here explore a new
region of the CO1 gene (CO1B) for DNA barcoding in 51 populations of 23 dragonfly
and damselfly species. We compare the "Folmer region", the mitochondrial ND1 gene
(NADH dehydrogenase 1) and the new CO1 region with regard to (i) speed and
reproducibility of sequence generation, (ii) levels of homoplasy and (iii)
numbers of diagnostic characters for discriminating closely related sister taxa
and populations. The performances of the gene regions regarding these criteria
were quite different. Both, the amplification of CO1B and ND1 was highly
reproducible and CO1B showed the highest potential for discriminating sister taxa
at different taxonomic levels. In contrast, the amplification of the "Folmer
region" using the universal primers was difficult and the third codon positions
of this fragment have experienced nucleotide substitution saturation. Most
important, exploring this new barcode region of the CO1 gene identified a higher
discriminating power between closely related sister taxa. Together with the
design of layered barcode approaches adapted to the specific taxonomic
"environment", this new marker will further enhance the discrimination power at
the species level.
PMID- 28406915
TI - Predicting functional decline and survival in amyotrophic lateral sclerosis.
AB - BACKGROUND: Better predictors of amyotrophic lateral sclerosis disease course
could enable smaller and more targeted clinical trials. Partially to address this
aim, the Prize for Life foundation collected de-identified records from
amyotrophic lateral sclerosis sufferers who participated in clinical trials of
investigational drugs and made them available to researchers in the PRO-ACT
database. METHODS: In this study, time series data from PRO-ACT subjects were
fitted to exponential models. Binary classes for decline in the total score of
amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R)
(fast/slow progression) and survival (high/low death risk) were derived. Data was
segregated into training and test sets via cross validation. Learning algorithms
were applied to the demographic, clinical and laboratory parameters in the
training set to predict ALSFRS-R decline and the derived fast/slow progression
and high/low death risk categories. The performance of predictive models was
assessed by cross-validation in the test set using Receiver Operator Curves and
root mean squared errors. RESULTS: A model created using a boosting algorithm
containing the decline in four parameters (weight, alkaline phosphatase, albumin
and creatine kinase) post baseline, was able to predict functional decline class
(fast or slow) with fair accuracy (AUC = 0.82). However similar approaches to
build a predictive model for decline class by baseline subject characteristics
were not successful. In contrast, baseline values of total bilirubin, gamma
glutamyltransferase, urine specific gravity and ALSFRS-R item score-climbing
stairs were sufficient to predict survival class. CONCLUSIONS: Using combinations
of small numbers of variables it was possible to predict classes of functional
decline and survival across the 1-2 year timeframe available in PRO-ACT. These
findings may have utility for design of future ALS clinical trials.
PMID- 28406916
TI - Applications of fractional lower order S transform time frequency filtering
algorithm to machine fault diagnosis.
AB - Stockwell transform(ST) time-frequency representation(ST-TFR) is a time frequency
analysis method which combines short time Fourier transform with wavelet
transform, and ST time frequency filtering(ST-TFF) method which takes advantage
of time-frequency localized spectra can separate the signals from Gaussian noise.
The ST-TFR and ST-TFF methods are used to analyze the fault signals, which is
reasonable and effective in general Gaussian noise cases. However, it is proved
that the mechanical bearing fault signal belongs to Alpha(alpha) stable
distribution process(1 < alpha < 2) in this paper, even the noise also is alpha
stable distribution in some special cases. The performance of ST-TFR method will
degrade under alpha stable distribution noise environment, following the ST-TFF
method fail. Hence, a new fractional lower order ST time frequency
representation(FLOST-TFR) method employing fractional lower order moment and ST
and inverse FLOST(IFLOST) are proposed in this paper. A new FLOST time frequency
filtering(FLOST-TFF) algorithm based on FLOST-TFR method and IFLOST is also
proposed, whose simplified method is presented in this paper. The discrete
implementation of FLOST-TFF algorithm is deduced, and relevant steps are
summarized. Simulation results demonstrate that FLOST-TFR algorithm is obviously
better than the existing ST-TFR algorithm under alpha stable distribution noise,
which can work better under Gaussian noise environment, and is robust. The FLOST
TFF method can effectively filter out alpha stable distribution noise, and
restore the original signal. The performance of FLOST-TFF algorithm is better
than the ST-TFF method, employing which mixed MSEs are smaller when alpha and
generalized signal noise ratio(GSNR) change. Finally, the FLOST-TFR and FLOST-TFF
methods are applied to analyze the outer race fault signal and extract their
fault features under alpha stable distribution noise, where excellent
performances can be shown.
PMID- 28406918
TI - A spatial method to calculate small-scale fisheries effort in data poor
scenarios.
AB - To gauge the collateral impacts of fishing we must know where fishing boats
operate and how much they fish. Although small-scale fisheries land approximately
the same amount of fish for human consumption as industrial fleets globally,
methods of estimating their fishing effort are comparatively poor. We present an
accessible, spatial method of calculating the effort of small-scale fisheries
based on two simple measures that are available, or at least easily estimated, in
even the most data-poor fisheries: the number of boats and the local coastal
human population. We illustrate the method using a small-scale fisheries case
study from the Gulf of California, Mexico, and show that our measure of Predicted
Fishing Effort (PFE), measured as the number of boats operating in a given area
per day adjusted by the number of people in local coastal populations, can
accurately predict fisheries landings in the Gulf. Comparing our values of PFE to
commercial fishery landings throughout the Gulf also indicates that the current
number of small-scale fishing boats in the Gulf is approximately double what is
required to land theoretical maximum fish biomass. Our method is fishery-type
independent and can be used to quantitatively evaluate the efficacy of growth in
small-scale fisheries. This new method provides an important first step towards
estimating the fishing effort of small-scale fleets globally.
PMID- 28406917
TI - Methylomic changes in individuals with psychosis, prenatally exposed to endocrine
disrupting compounds: Lessons from diethylstilbestrol.
AB - BACKGROUND: In the Western world, between 1940 and 1970, more than 2 million
people were exposed in utero to diethylstilbestrol (DES). In exposed individuals,
and in their descendants, adverse outcomes have been linked to such exposure,
including cancers, genital malformations, and less consistently, psychiatric
disorders. We aimed to explore whether prenatal DES exposure would be associated
with DNA methylation changes, and whether these epigenetic modifications would be
associated with increased risk of psychosis. METHODS: From 247 individuals born
from mothers exposed to DES, we selected 69 siblings from 30 families. In each
family, at least one sibling was exposed in utero to DES. We performed a
methylome-wide association study using HumanMethylation450 DNA Analysis
BeadChip(r) in peripheral blood. We analyzed methylation changes at individual
CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We
also compared exposed individuals with (n = 7) and without psychosis (n = 30).
RESULTS: There were more individuals with schizophrenia in the DES-exposed group.
We found no significant differences between exposed and unexposed individuals
with respect to differentially methylated CpGs or regions. The largest difference
was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9).
Compared to exposed individuals without psychosis, exposed individuals with
psychosis had differential methylation in the region encompassing the gene
encoding the zinc finger protein 57 (ZFP57). CONCLUSIONS: In utero exposure to
DES was not associated with methylation changes at specific CpG or regions. In
exposed individuals, however, psychosis was associated with specific methylomic
modifications that could impact neurodevelopment and neuroplasticity.
PMID- 28406919
TI - What are the assets and weaknesses of HFO detectors? A benchmark framework based
on realistic simulations.
AB - High-frequency oscillations (HFO) have been suggested as biomarkers of epileptic
tissues. While visual marking of these short and small oscillations is tedious
and time-consuming, automatic HFO detectors have not yet met a large consensus.
Even though detectors have been shown to perform well when validated against
visual marking, the large number of false detections due to their lack of
robustness hinder their clinical application. In this study, we developed a
validation framework based on realistic and controlled simulations to quantify
precisely the assets and weaknesses of current detectors. We constructed a
dictionary of synthesized elements-HFOs and epileptic spikes-from different
patients and brain areas by extracting these elements from the original data
using discrete wavelet transform coefficients. These elements were then added to
their corresponding simulated background activity (preserving patient- and region
specific spectra). We tested five existing detectors against this benchmark.
Compared to other studies confronting detectors, we did not only ranked them
according their performance but we investigated the reasons leading to these
results. Our simulations, thanks to their realism and their variability, enabled
us to highlight unreported issues of current detectors: (1) the lack of robust
estimation of the background activity, (2) the underestimated impact of the 1/f
spectrum, and (3) the inadequate criteria defining an HFO. We believe that our
benchmark framework could be a valuable tool to translate HFOs into a clinical
environment.
PMID- 28406920
TI - Experimental and mathematical analysis of cAMP nanodomains.
AB - In their role as second messengers, cyclic nucleotides such as cAMP have a
variety of intracellular effects. These complex tasks demand a highly organized
orchestration of spatially and temporally confined cAMP action which should be
best achieved by compartmentalization of the latter. A great body of evidence
suggests that cAMP compartments may be established and maintained by cAMP
degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and
biophysical details of how PDEs can orchestrate cAMP gradients are entirely
unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in
living cells, we provide direct experimental evidence that the cAMP concentration
in the vicinity of an individual PDE molecule is below the detection limit of our
FRET sensors (<100nM). This cAMP gradient persists in crude cytosol preparations.
We developed mathematical models based on diffusion-reaction equations which
describe the creation of nanocompartments around a single PDE molecule and more
complex spatial PDE arrangements. The analytically solvable equations derived
here explicitly determine how the capability of a single PDE, or PDE complexes,
to create a nanocompartment depend on the cAMP degradation rate, the diffusive
mobility of cAMP, and geometrical and topological parameters. We apply these
generic models to our experimental data and determine the diffusive mobility and
degradation rate of cAMP. The results obtained for these parameters differ by far
from data in literature for free soluble cAMP interacting with PDE. Hence,
restricted cAMP diffusion in the vincinity of PDE is necessary to create cAMP
nanocompartments in cells.
PMID- 28406921
TI - Is the risk of progressive multifocal leukoencephalopathy the real reason for
natalizumab discontinuation in patients with multiple sclerosis?
AB - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is one of the major
risks of natalizumab therapy. Despite introduction of the currently employed PML
risk stratification algorithm, the incidence of natalizumab-associated PML cases
is not decreasing. OBJECTIVES: We addressed the following questions: How do
natalizumab-treated multiple sclerosis patients and their treating physicians
assess and deal with PML risk? Is PML risk the real reason for natalizumab
discontinuation? METHODS: 699 natalizumab-treated multiple sclerosis patients and
99 physicians were included in this prospective observational study.
Questionnaires were completed at 5 different time points. Patients were
stratified into 5 subgroups according to the presence of PML risk factors (prior
immunosuppression, anti-JCV antibody status, treatment duration). Patients with
prior immunosuppression (n = 30, treated by n = 7 physicians) were excluded from
analyses, because patient numbers were too small. Patients' anti-JCV antibody
index was not considered because data recruitment ended in 2014. Using Bayesian
network and regression analysis, we examined the relationship between different
patient- and physician-related factors and patients' discontinuation of
natalizumab. RESULTS: Patients of all subgroups and physicians assessed the PML
risk as low. Overall patient adherence to natalizumab was high (87%). Only 13% of
patients discontinued therapy. Natalizumab treatment cessation was associated
with different patient- and physician-related factors (physicians' assessment of
general PML risk, number of treated patients per year, natalizumab treatment
duration, relapses during the course of study) upon which only physicians'
judgment on treatment continuation, patients' perception of personal PML risk,
and JCV seroconversion showed significant relationships. CONCLUSION: According to
the currently employed risk stratification algorithm, the objective PML risk
probably doesn't play a dominant role in a patients' decision to continue or stop
natalizumab treatment. The decision-making process is rather guided by subjective
views and experiences of patients and treating neurologists. Treating physicians
should consider this discrepancy in their advice to improve the risk-benefit
ratio for the individual patient.
PMID- 28406923
TI - Model selection with multiple regression on distance matrices leads to incorrect
inferences.
AB - In landscape genetics, model selection procedures based on Information Theoretic
and Bayesian principles have been used with multiple regression on distance
matrices (MRM) to test the relationship between multiple vectors of pairwise
genetic, geographic, and environmental distance. Using Monte Carlo simulations,
we examined the ability of model selection criteria based on Akaike's information
criterion (AIC), its small-sample correction (AICc), and the Bayesian information
criterion (BIC) to reliably rank candidate models when applied with MRM while
varying the sample size. The results showed a serious problem: all three criteria
exhibit a systematic bias toward selecting unnecessarily complex models
containing spurious random variables and erroneously suggest a high level of
support for the incorrectly ranked best model. These problems effectively
increased with increasing sample size. The failure of AIC, AICc, and BIC was
likely driven by the inflated sample size and different sum-of-squares
partitioned by MRM, and the resulting effect on delta values. Based on these
findings, we strongly discourage the continued application of AIC, AICc, and BIC
for model selection with MRM.
PMID- 28406922
TI - 3D fabrication and characterization of phosphoric acid scaffold with a HA/beta
TCP weight ratio of 60:40 for bone tissue engineering applications.
AB - A key requirement for three-dimensional printing (3-DP) at room temperature of
medical implants depends on the availability of printable and biocompatible
binder-powder systems. Different concentration polyvinyl alcohol (PVA) and
phosphoric acid solutions were chosen as the binders to make the artificial stent
biocompatible with sufficient compressive strength. In order to achieve an
optimum balance between the bioceramic powder and binder solution, the
biocompatibility and mechanical properties of these artificial stent samples were
tested using two kinds of binder solutions. This study demonstrated the printable
binder formulation at room temperature for the 3D artificial bone scaffolds. 0.6
wt% PVA solution was ejected easily via inkjet printing, with a supplementation
of 0.25 wt% Tween 80 to reduce the surface tension of the polyvinyl alcohol
solution. Compared with the polyvinyl alcohol scaffolds, the phosphoric acid
scaffolds had better mechanical properties. Though both scaffolds supported the
cell proliferation, the absorbance of the polyvinyl alcohol scaffolds was higher
than that of the phosphoric acid scaffolds. The artificial stents with a
hydroxyapatite/beta-tricalcium phosphate (HA/beta-TCP) weight ratios of 60:40
depicted good biocompatibility for both scaffolds. Considering the scaffolds'
mechanical and biocompatible properties, the phosphoric acid scaffolds with a
HA/beta-TCP weight ratio of 60:40 may be the best combination for bone tissue
engineering applications.
PMID- 28406924
TI - Quantifying dispersal of a non-aggressive saprophytic bark beetle.
AB - Long distance dispersal to locate suitable breeding sites is recognized as a key
trait influencing the population dynamics and distribution of bark beetles and
other saprophytic insects. While dispersal behavior has been studied for a range
of aggressive 'tree killing' bark beetles, few have considered the dispersal
behaviour of non-aggressive saprophytic bark beetles that utilize kairomones
(host volatiles). We present the results of a mark-recapture experiment that
examined adult dispersal patterns of the saprophytic bark beetle Hylurgus
ligniperda. Releases took place in summer and autumn 2014, in a clearcut pine
forest in the central North Island, New Zealand. Both flight-experienced and
flight-naive adults were marked and released in the center of a circular trap
grid that extended to 960 m with 170 or 200 panel traps baited with a kairomone
blend of alpha-pinene and ethanol. Of the 18,464 released H. ligniperda, 9,209
(49.9%) of the beetles flew, and 96 (1.04%) of the beetles that flew were
recaptured. Individuals were recaptured at all distances. The recapture of flight
experienced beetles declined with dispersal distance, and a diffusion model
showed heterogeneous dispersal tendencies within the population. Our best model
estimated that 46% of flight-experienced beetles disperse > 1 km, and 1.6% > 5
km. Conversely, no declining pattern was shown in the recapture of flight-naive
beetles, suggesting that emerging H. ligniperda may require a period of flight to
initiate chemotropic orientation behavior and subsequent attraction to traps. We
discuss the implications of these findings for the management of phytosanitary
risks. For instance, combining landscape knowledge of source populations with
dispersal processes facilitates estimation of pest pressure at economically
sensitive areas such as harvest and timber storage sites. Quantitative dispersal
estimates also inform pest risk assessments by predicting spread rates for H.
ligniperda that has proven establishment capabilities in other countries.
PMID- 28406925
TI - Characterization of a thermophilic cellulase from Geobacillus sp. HTA426, an
efficient cellulase-producer on alkali pretreated of lignocellulosic biomass.
AB - A themophilic cellulase-producing bacterium was isolated from a hot spring
district and identified as Geobacillus sp. HTA426. The cellulase enzyme produced
by the Geobacillus sp. HTA426 was purified through ammonium sulfate precipitation
and ion exchange chromatography, with the recovery yield and fold purification of
10.14% and 5.12, respectively. The purified cellulase has a molecular weight of
40 kDa. The optimum temperature and pH for carboxymethyl cellulase (CMCase)
activity of the purified cellulase were 60 degrees C and pH 7.0, respectively.
The enzyme was also stable over a wide temperature range of 50 degrees C to 70
degrees C after 5 h of incubation. Moreover, the strain HTA426 was able to grow
and produce cellulase on alkali-treated sugarcane bagasse, rice straw and water
hyacinth as carbon sources. Enzymatic hydrolysis of sugarcane bagasse, which was
regarded as the most effective carbon source for cellulase production (CMCase
activity = 103.67 U/mL), followed by rice straw (74.70 U/mL) and water hyacinth
(51.10 U/mL). This strain producing an efficient thermostable cellulose is a
potential candidate for developing a more efficient and cost-effective process
for converting lignocellulosic biomass into biofuel and other industrial process.
PMID- 28406926
TI - High-resolution respirometry of fine-needle muscle biopsies in pre-manifest
Huntington's disease expansion mutation carriers shows normal mitochondrial
respiratory function.
AB - Alterations in mitochondrial respiration are an important hallmark of
Huntington's disease (HD), one of the most common monogenetic causes of
neurodegeneration. The ubiquitous expression of the disease causing mutant
huntingtin gene raises the prospect that mitochondrial respiratory deficits can
be detected in skeletal muscle. While this tissue is readily accessible in
humans, transgenic animal models offer the opportunity to cross-validate findings
and allow for comparisons across organs, including the brain. The integrated
respiratory chain function of the human vastus lateralis muscle was measured by
high-resolution respirometry (HRR) in freshly taken fine-needle biopsies from
seven pre-manifest HD expansion mutation carriers and nine controls. The
respiratory parameters were unaffected. For comparison skeletal muscle isolated
from HD knock-in mice (HdhQ111) as well as a broader spectrum of tissues
including cortex, liver and heart muscle were examined by HRR. Significant
changes of mitochondrial respiration in the HdhQ knock-in mouse model were
restricted to the liver and the cortex. Mitochondrial mass as quantified by
mitochondrial DNA copy number and citrate synthase activity was stable in murine
HD-model tissue compared to control. mRNA levels of key enzymes were determined
to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated
the feasibility to perform high-resolution respirometry measurements from small
human HD muscle biopsies. Furthermore, we conclude that alterations in
respiratory parameters of pre-manifest human muscle biopsies are rather limited
and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle.
In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations
highlighting the tissue specific nature of mutant huntingtin effects on
respiration.
PMID- 28406927
TI - Application of a household-based molecular xenomonitoring strategy to evaluate
the lymphatic filariasis elimination program in Tamil Nadu, India.
AB - BACKGROUND: The monitoring and evaluation of lymphatic filariasis (LF) has
largely relied on the detection of antigenemia and antibodies in human
populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in
mosquitoes, may be an effective complementary method, particularly for detecting
signals in low-level prevalence areas where Culex is the primary mosquito vector.
This paper investigated the application of a household-based sampling method for
MX in Tamil Nadu, India. METHODS: MX surveys were conducted in 2010 in two
evaluation units (EUs): 1) a hotspot area, defined as sites with community
microfilaria prevalence >=1%, and 2) a larger area that also encompassed the
hotspots. Households were systematically selected using a sampling interval
proportional to the number of households in the EU. Mosquito pools were collected
and analyzed by real-time polymerase chain reaction (qPCR). Two independent
samples were taken in each EU to assess reproducibility of results. Follow-up
surveys were conducted in 2012. RESULTS: In 2010, the proportion of positive
pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012,
pool positivity was significantly reduced to 24.3% and 6.5%, respectively
(p<0.0001). Pool positivity based on independent samples taken from each EU in
2010 and 2012 were not significantly different except for the hotspot EU in 2012
(p = 0.009). The estimated prevalence of infection in mosquitoes, measured by
PoolScreen, declined from 2.2-2.7% in 2010 to 0.6-1.2% in 2012 in the hotspot
area and from 0.9-1.1% to 0.2-0.3% in the larger area. CONCLUSIONS: The household
based sampling strategy for MX led to mostly reproducible results and supported
the observed LF infection trends found in humans. MX has the potential to be a
cost-effective, non-invasive monitoring and evaluation tool with sensitive
detection of infection signals in low prevalence settings. Further investigation
and application of this sampling strategy for MX are recommended to support its
adoption as a standardized method for global LF elimination programs.
PMID- 28406928
TI - Fibroblast-growth factor 23 promotes terminal differentiation of ATDC5 cells.
AB - OBJECTIVES: Fibroblast Growth Factor 23 (FGF23) is well documented as a crucial
player in the systemic regulation of phosphate homeostasis. Moreover, loss-of
function experiments have revealed that FGF23 also has a phosphate-independent
and local impact on skeletogenesis. Here, we used ATDC5 cell line to investigate
the expression of FGF23 and the role it may play locally during the
differentiation of these cells. METHODS: ATDC5 cells were differentiated in the
presence of insulin, and treated with recombinant FGF23 (rFGF23), inorganic
phosphate (Pi) and/or PD173074, an inhibitor of FGF receptors (FGFRs). The mRNA
expressions of FGF23, FGFRs and markers of hypertophy, Col X and MMP13, were
determined by qPCR analysis and FGF23 production was assessed by ELISA. FGFR
activation was determined by immunoprecipitation and immunoblotting. RESULTS:
FGF23 mRNA expression and production were increased during ATDC5 differentiation.
At D28 in particular, rFGF23 stimulation increased hypertrophic markers
expression, as Col X and MMP13, and mineralization. A synergic effect of Pi and
rFGF23 stimulation was observed on these markers and on the mineralization
process. The use of PD173074, a pan-FGFR inhibitor, decreased terminal
differentiation of ATDC5 by preventing rFGF23 pro-hypertrophic effects.
CONCLUSIONS: Altogether, our results provide evidence that FGF23 plays an
important role during differentiation of ATDC5 cell line, by promoting both
hypertrophy and mineralization.
PMID- 28406929
TI - HIV/AIDS knowledge, attitudes and behaviour of persons with and without
disabilities from the Uganda Demographic and Health Survey 2011: Differential
access to HIV/AIDS information and services.
AB - Uganda is among the first to use the Washington Group Short Set of Questions on
Disability to identify persons with disabilities in its Demographic and Health
Survey. In this paper, we review the HIV Knowledge, Attitudes and Behaviour
component of the 2011 Ugandan Demographic and Health Survey, analysing a series
of questions comparing those with and without disabilities in relation to
HIV/AIDS knowledge, attitudes and practices. We found comparable levels of
knowledge on HIV/AIDS for those with and those without disabilities in relation
to HIV transmission during delivery (93.89%, 93.26%) and through breastfeeding
(89.91%, 90.63%), which may reflect increased attention to reaching the community
of persons with disabilities. However, several gaps in the knowledge base of
persons with disabilities stood out, including misconceptions of risk of HIV
infection through mosquito bites and caring for a relative with HIV in own
household (34.39%, 29.86%; p<0.001; 91.53%, 89.00%; p = 0.001, respectively). The
issue is not just access to appropriate information but also equitable access to
HIV/AIDS services and support. Here we found that persons with multiple
disabilities were less likely than individuals without disabilities to return to
receive results from their most recent HIV test (0.60[0.41-0.87], p<0.05). HIV
testing means little if people do not return for follow-up to know their HIV
status and, if necessary, to be connected to available services and supports.
Additional findings of note were that persons with disabilities reported having a
first sexual encounter at a slightly younger age than peers without disabilities;
and persons with disabilities also reported having a sexually transmitted disease
(STD) within the last 12 months at significantly higher rates than peers without
disabilities (1.38[1.18-1.63], p<0.01), despite reporting comparable knowledge of
the need for safer sex practices. This analysis is among the first to use
HIV/AIDS-related questions from Demographic Health Surveys to provide information
about persons with disabilities in Uganda in comparison to those without
disabilities. These findings present a more complex and nuanced understanding of
persons with disabilities and HIV/AIDS. If persons with disabilities are becoming
sexually active earlier, are more likely to have an STD within the preceding 12
month period and are less likely to receive HIV test results, it is important to
understand why. Recommendations are also made for the inclusion of disability
measures in Uganda's AIDS Indicator Survey to provide cyclical and systematic
data on disability and HIV/AIDS, including HIV prevalence amongst persons with
disabilities.
PMID- 28406930
TI - Eutopic/ectopic endometrial apoptosis initiated by bilateral uterine artery
occlusion: A new therapeutic mechanism for uterus-sparing surgery in adenomyosis.
AB - The objective of the present study was to investigate differences in the
expression of apoptosis-related factors in the eutopic and ectopic endometrium
(EuE/EE) in women with adenomyosis before and after laparoscopic bilateral
uterine artery occlusion (LUAO). Ten patients with uterine adenomyosis who
received LUAO were selected as the research subjects, from whom EuE and EE
tissues were obtained before and after LUAO and detected for the expression of
apoptosis-related molecules in EuE and EE by PT-PCR and Western blot, and changes
in the mitochondrial structure by electron microscopy. Normal endometrial stromal
cells (NESC), and EuE/EE stromal cells in women with adenomyosis were cultured in
a 1% O2, 5% CO2 incubator to establish a physical anoxia state in an in vitro
stromal cell model. The expression of apoptosis-related molecules was observed at
0, 6, 12, 24 and 48h of hypoxic. The results showed that the expression of
apoptosis-related factors in EuE and EE were increased significantly after LUAO
and under hypoxic conditions in vitro, suggesting that transient ischemia and
hypoxia were involved in the apoptosis of adenomysis lesions, and that uterine
artery occlusion could remove adenomyosis lesions on tissue/cell level by
cytoreduction, thus reaching the goal of treating adenomyosis effectively.
PMID- 28406931
TI - A model of Periventricular Leukomalacia (PVL) in neonate mice with
histopathological and neurodevelopmental outcomes mimicking human PVL in
neonates.
AB - Periventricular leukomalacia (PVL), a brain injury affecting premature infants is
commonly associated with cerebral palsy. PVL results from hypoxia-ischemia (HI)
with or without infection and is characterized by white matter necrotic lesions,
hypomyelination, microglial activation, astrogliosis, and neuronal death. It is
important to study a PVL mouse model that mimics human PVL in symptomatology,
anatomic and molecular basis. In our neonate mice model, bilateral carotid
arteries were temporary ligated at P5 followed by hypoxic exposure (FiO2 of 8%
for 20 min.). At P5 in mice, the white matter is more vulnerable to HI injury
than the grey matter. In our PVL model, mice suffer from significant hind limb
paresis, incoordination and feeding difficulties. Histologically they present
with ventriculomegally, white matter loss, microglial activation and neuronal
apoptosis. HI injury increases proinflammtory cytokines, activates NF-kB,
activates microglia and causes nitrative stress. All these inflammatory mediators
lead to oligodendroglial injury and white matter loss. Neurobehavioral analysis
in the PVL mice model at P60 showed that the HI group had a significant decrease
in hind limb strength, worsening rotarod testing and worsening performance in the
open field test. This new PVL model has great advantages far beyond just
mimicking human PVL in clinical features and histopathology. Long term survival,
the development of cerebral palsy and the ability of using this model in
transgenic animals will increase our understanding of the mechanistic pathways
underlying PVL and defining specific targets for the development of suitable
therapeutics.
PMID- 28406932
TI - A comparison of stimulus types in online classification of the P300 speller using
language models.
AB - The P300 Speller is a common brain-computer interface communication system. There
are many parallel lines of research underway to overcome the system's low signal
to noise ratio and thereby improve performance, including using famous face
stimuli and integrating language information into the classifier. While both have
been shown separately to provide significant improvements, the two methods have
not yet been implemented together to demonstrate that the improvements are
complimentary. The goal of this study is therefore twofold. First, we aim to
compare the famous faces stimulus paradigm with an existing alternative stimulus
paradigm currently used in commercial systems (i.e., character inversion).
Second, we test these methods with language model integration to assess whether
different optimization approaches can be combined to further improve BCI
communication. In offline analysis using a previously published particle filter
method, famous faces stimuli yielded superior results to both standard and
inverting stimuli. In online trials using the particle filter method, all 10
subjects achieved a higher selection rate when using the famous faces flashing
paradigm than when using inverting flashes. The improvements achieved by these
methods are therefore complementary and a combination yields superior results to
either method implemented individually when tested in healthy subjects.
PMID- 28406933
TI - Transcriptomic profiling of taproot growth and sucrose accumulation in sugar beet
(Beta vulgaris L.) at different developmental stages.
AB - In sugar beet (Beta vulgaris L.), taproot weight and sucrose content are the
important determinants of yield and quality. However, high yield and low sucrose
content are two tightly bound agronomic traits. The advances in next-generation
sequencing technology and the publication of sugar beet genome have provided a
method for the study of molecular mechanism underlying the regulation of these
two agronomic traits. In this work, we performed comparative transcriptomic
analyses in the high taproot yield cultivar SD13829 and the high sucrose content
cultivar BS02 at five developmental stages. More than 50,000,000 pair-end clean
reads for each library were generated. When taproot turned into the rapid growth
stage at the growth stage of 82 days after emergence (DAE), eighteen enriched
gene ontology (GO) terms, including cell wall, cytoskeleton, and enzyme linked
receptor protein signaling pathway, occurred in both cultivars. Differentially
expressed genes (DEGs) of paired comparison in both cultivars were enriched in
the cell wall GO term. For pathway enrichment analyses of DEGs that were
respectively generated at 82 DAE compared to 59 DAE (the earlier developmental
stage before taproot turning into the rapid growth stage), plant hormone signal
transduction pathway was enriched. At 82 DAE, the rapid enlarging stage of
taproot, several transcription factor family members were up-regulated in both
cultivars. An antagonistic expression of brassinosteroid- and auxin-related genes
was also detected. In SD13829, the growth strategy was relatively focused on cell
enlargement promoted by brassinosteroid signaling, whereas in BS02, it was
relatively focused on secondarily cambial cell division regulated by cytokinin,
auxin and brassinosteroid signaling. Taken together, our data demonstrate that
the weight and sucrose content of taproot rely on its growth strategy, which is
controlled by brassinosteroid, auxin, cytokinin, and gibberellin.
PMID- 28406935
TI - Micro-level explanations for emergent patterns of self-governance arrangements in
small-scale fisheries-A modeling approach.
AB - Small-scale fisheries (SSFs) in developing countries are expected to play a
significant role in poverty alleviation and enhancing food security in the
decades to come. To realize this expectation, a better understanding of their
informal self-governance arrangements is critical for developing policies that
can improve fishers' livelihoods and lead to sustainable ecosystem stewardship.
The goal of this paper is to develop a more nuanced understanding of micro-level
factors-such as fishers' characteristics and behavior-to explain observed
differences in self-governance arrangements in Northwest Mexico. We focus on two
ubiquitous forms of self-governance: hierarchical non-cooperative arrangements
between fishers and fishbuyers, such as patron-client relationships (PCs), versus
more cooperative arrangements amongst fishers, such as fishing cooperatives (co
ops). We developed an agent-based model of an archetypical SSF that captures key
hypotheses from in-depth fieldwork in Northwest Mexico of fishers' day-to-day
fishing and trading. Results from our model indicate that high diversity in
fishers' reliability, and low initial trust between co-op members, makes co-ops'
establishment difficult. PCs cope better with this kind of diversity because, in
contrast to co-ops, they have more flexibility in choosing whom to work with.
However, once co-ops establish, they cope better with seasonal variability in
fish abundance and provide long-term security for the fishers. We argue that
existing levels of trust and diversity among fishers matter for different self
governance arrangements to establish and persist, and should therefore be taken
into account when developing better, targeted policies for improved SSFs
governance.
PMID- 28406934
TI - DaT-SPECT assessment depicts dopamine depletion among asymptomatic G2019S LRRK2
mutation carriers.
AB - Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging
expected in the prodromal phase of Parkinson's disease (PD), are usually
overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk
for developing PD, compared to non-carriers. In this work we aimed to study early
changes in Dopamine uptake in non-manifesting PD carriers (NMC) of the G2019S
LRRK2 mutation using quantitative DaT-SPECT analysis and to examine the potential
for early prediction of PD. Eighty Ashkenazi-Jewish subjects were included in
this study: eighteen patients with PD; thirty-one NMC and thirty-one non
manifesting non-carriers (NMNC). All subjects underwent a through clinical
assessment including evaluation of motor, olfactory, affective and non-motor
symptoms and DaT-SPECT imaging. A population based DaT-SPECT template was created
based on the NMNC cohort, and data driven volumes-of-interest (VOIs) were
defined. Comparisons between groups were performed based on VOIs and voxel-wise
analysis. The striatum area of all three cohorts was segmented into four VOIs,
corresponding to the right/left dorsal and ventral striatum. Significant
differences in clinical measures were found between patients with PD and non
manifesting subjects with no differences between NMC and NMNC. Significantly
lower uptake (p<0.001) was detected in the right and left dorsal striatum in the
PD group (2.2+/-0.3, 2.3+/-0.4) compared to the NMC (4.2+/-0.6, 4.3+/-0.5) and
NMNC (4.5+/-0.6, 4.6+/-0.6), and significantly (p = 0.05) lower uptake in the
right dorsal striatum in the NMC group compared to NMNC. Converging results were
obtained using voxel-wise analysis. Two NMC participants, who later
phenoconverted into PD, demonstrated reduced uptake mainly in the dorsal
striatum. No significant correlations were found between the DaT-SPECT uptake in
the different VOIs and clinical and behavioral assessments in the non-manifesting
groups. This study shows the clinical value of quantitative assessment of DaT
SPECT imaging and the potential for predicting PD by detection of dopamine
depletion, already at the pre-symptomatic stage. Clinical registration numbers:
NCT01089270 and NCT01089283.
PMID- 28406936
TI - Enhancing consolidation of a rotational visuomotor adaptation task through acute
exercise.
AB - We assessed the effect of a single bout of intense exercise on the adaptation and
consolidation of a rotational visuomotor task, together with the effect of the
order of exercise presentation relative to the learning task. Healthy adult
participants (n = 29) were randomly allocated to one of three experimental
groups: (1) exercise before task practice, (2) exercise after task practice, and
(3) task practice only. After familiarization with the learning task,
participants undertook a baseline practice set. Then, four 60 degrees clockwise
rotational sets were performed, comprising an adaptation set and three retention
sets at 1 h, 24 h, and 7 days after the adaptation set. Depending on the
experimental group, exercise was presented before or after the adaptation sets.
We found that error reduction during adaptation was similar regardless of when
exercise was presented. During retention, significant error reduction was found
in the retention set at 1 h for both exercise groups, but this enhancement was
not present during subsequent retention sets, with no differences present between
exercise groups. We conclude that an acute bout of intense exercise could
positively affect retention, although the order in which exercise is presented
does not appear to influence its benefits during the early stages of
consolidation.
PMID- 28406937
TI - Cost and time-effective method for multi-scale measures of rugosity, fractal
dimension, and vector dispersion from coral reef 3D models.
AB - We present a method to construct and analyse 3D models of underwater scenes using
a single cost-effective camera on a standard laptop with (a) free or low-cost
software, (b) no computer programming ability, and (c) minimal man hours for both
filming and analysis. This study focuses on four key structural complexity
metrics: point-to-point distances, linear rugosity (R), fractal dimension (D),
and vector dispersion (1/k). We present the first assessment of accuracy and
precision of structure-from-motion (SfM) 3D models from an uncalibrated GoProTM
camera at a small scale (4 m2) and show that they can provide meaningful,
ecologically relevant results. Models had root mean square errors of 1.48 cm in X
Y and 1.35 in Z, and accuracies of 86.8% (R), 99.6% (D at scales 30-60 cm), 93.6%
(D at scales 1-5 cm), and 86.9 (1/k). Values of R were compared to in-situ chain
and-tape measurements, while values of D and 1/k were compared with ground truths
from 3D printed objects modelled underwater. All metrics varied less than 3%
between independently rendered models. We thereby improve and rigorously validate
a tool for ecologists to non-invasively quantify coral reef structural complexity
with a variety of multi-scale metrics.
PMID- 28406939
TI - Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.
AB - The mechanism of the negative regulation of proopiomelanocortin gene (Pomc) by
glucocorticoids (Gcs) is still unclear in many points. Here, we demonstrated the
involvement of neurogenic differentiation factor 1 (NeuroD1) in the Gc-mediated
negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH)
producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone
(DEX) (1-100 nM) and cultured for 24 hrs. Thereafter, Pomc mRNA expression was
studied by quantitative real-time PCR and rat Pomc promoter (-703/+58) activity
was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter
activity were inhibited by DEX in a dose-dependent manner. Deletion and point
mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional
repression was mediated via E-box that exists at -376/-371 in the promoter. Since
NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next
examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose
dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb)
activity, and NeuroD1 protein expression in AtT20 cells. In addition, we
confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on
Pomc promoter by chromatin immunoprecipitation (ChIP) assay. Finally,
overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc
mRNA expression and Pomc promoter activity. Taken together, it is suggested that
the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box
interaction may play an important role in the Gc-mediated negative regulation of
Pomc.
PMID- 28406938
TI - Dual effect of fetal bovine serum on early development depends on stage-specific
reactive oxygen species demands in pigs.
AB - Despite the application of numerous supplements to improve in vitro culture (IVC)
conditions of mammalian cells, studies regarding the effect of fetal bovine serum
(FBS) on mammalian early embryogenesis, particularly in relation to redox
homeostasis, are lacking. Herein, we demonstrated that early development of in
vitro-produced (IVP) porcine embryos highly depends on the combination of FBS
supplementation timing and embryonic reactive oxygen species (ROS) requirements.
Interestingly, FBS significantly reduced intracellular ROS levels in
parthenogenetically activated (PA) embryos regardless of the developmental stage.
However, the beneficial effect of FBS on early embryogenesis was found only
during the late phase (IVC 4-6 days) treatment group. In particular,
developmental competence parameters, such as blastocyst formation rate, cellular
survival, total cell number and trophectoderm proportion, were markedly increased
by FBS supplementation during the late IVC phase. In addition, treatment with FBS
elevated antioxidant transcript levels during the late IVC phase. In contrast,
supplementation with FBS during the entire period (1-6 days) or during the early
IVC phase (1-2 days) greatly impaired the developmental parameters. Consistent
with the results from PA embryos, the developmental competence of in vitro
fertilization (IVF) or somatic cell nuclear transfer (SCNT) embryos were markedly
improved by treatment with FBS during the late IVC phase. Moreover, the embryonic
stage-specific effects of FBS were reversed by the addition of an oxidant and
were mimicked by treatment with an antioxidant. These findings may increase our
understanding of redox-dependent early embryogenesis and contribute to the large
scale production of high-quality IVP embryos.
PMID- 28406940
TI - Early prediction of postoperative liver dysfunction and clinical outcome using
antithrombin III-activity.
AB - BACKGROUND AND AIMS: Antithrombin III (ATIII) has been reported to be associated
with liver pathologies and was shown to predict outcome in patients undergoing
liver resection for hepatocellular carcinoma. We now aimed to assess whether
perioperative ATIII-activity could predict postoperative outcome in patients
without underlying liver disease, as well as in a routine clinical setting of
patients undergoing hepatic resection. METHODS: ATIII-activity was evaluated
preoperatively and on the first (POD1) and fifth day after liver resection in a
retrospective evaluation cohort of 228 colorectal cancer patients with liver
metastasis (mCRC). We further aimed to prospectively validate our results in a
set of 177 consecutive patients undergoing hepatic resection. RESULTS: Patients
developing postoperative liver dysfunction (LD) had a more pronounced
postoperative decrease in ATIII-activity (P<0.001). ATIII-activity on POD1
significantly predicted postoperative LD (P<0.001, AUC = 84.4%) and remained
independent upon multivariable analysis. A cut-off value of 61.5% ATIII-activity
was determined using ROC analysis. This cut-off was vital to identify high-risk
patients for postoperative LD, morbidity, severe morbidity and mortality
(P<0.001, respectively) with a highly accurate negative predictive value of 97%,
which could be confirmed for LD (P<0.001) and mortality (P = 0.014) in our
independent validation cohort. Further, mCRC patients below our cut-off suffered
from a significantly decreased overall survival (OS) at 1 and 3 years after
surgery (P = 0.011, P = 0.025). CONCLUSIONS: The routine laboratory parameter
ATIII-activity on POD1 independently predicted postoperative LD and was
associated with clinical outcome. Patients with a postoperative ATIII-activity
<61.5% might benefit from close monitoring and timely initiation of supportive
therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01700231.
PMID- 28406941
TI - Association of diabetes mellitus with decline in ankle-brachial index among
patients on hemodialysis: A 6-year follow-up study.
AB - Peripheral artery occlusive disease is common among diabetes mellitus (DM) and
end-stage renal disease patients, and tends to progress faster and lead to worse
outcomes. This study compared the association of DM with the decline in ankle
brachial index (ABI) among patients on hemodialysis (HD). This was a longitudinal
analysis of ABI in HD patients from 2009 to 2015. Medical records and yearly ABI
values were obtained. A longitudinal mixed-model analysis was used to evaluate
ABI changing trends while accounting for within-patients correlation. There were
296 patients on HD in the period of 2009-2015. In a 6-year follow-up, those with
DM had a more rapid ABI decline compared to non-DM patients (slopes: -0.014 vs.
0.010 per year, interaction p < 0.001). In DM patients, female sex, high pulse
pressure, high triglyceride, low creatinine, and high uric acid were associated
with a decrease in ABI. In non-DM patients, old age, high pulse pressure, high
low-density lipoprotein cholesterol, and high uric acid were associated with a
decreased in ABI. There were 49.6% of patients with a normal ABI experienced a
decrease at least 0.1 of ABI from baseline, and 35.3% had a final ABI < 0.9 in
patients with a baseline ABI >= 0.9 (n = 232). In this study, DM patients on HD
tend to develop a more rapid decline in ABI than non-DM patients on HD. Age, sex,
pulse pressure, lipid profile, creatinine, and uric acid are associated with a
decreased in ABI.
PMID- 28406942
TI - The brain anatomy of attention-deficit/hyperactivity disorder in young adults - a
magnetic resonance imaging study.
AB - BACKGROUND: This is one of the first studies to examine the structural brain
anatomy and connectivity associated with an ADHD diagnosis and child as well as
adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD
diagnosis and in particular childhood symptoms, are associated with widespread
changes in the brain macro- and microstructure, which can be used to develop a
morphometric biomarker for ADHD. METHODS: Voxel-wise linear regression models
were used to examine structural and diffusion-weighted MRI data in 72
participants (31 young adults with ADHD and 41 controls without ADHD) in relation
to diagnosis and the number of self-reported child and adult symptoms. RESULTS:
Findings revealed significant associations between ADHD diagnosis and widespread
changes to the maturation of white matter fiber bundles and gray matter density
in the brain, such as structural shape changes (incomplete maturation) of the
middle and superior temporal gyrus, and fronto-basal portions of both frontal
lobes. ADHD symptoms in childhood showed the strongest association with brain
macro- and microstructural abnormalities. At the brain circuitry level, the
superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional
in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis
correctly up to 83% of all cases. CONCLUSION: An adult ADHD diagnosis and in
particular childhood symptoms are associated with widespread micro- and
macrostructural changes. The SLF and cortico-limbic findings suggest complex
audio-visual, motivational, and emotional dysfunctions associated with ADHD in
young adults. The sensitivity of the morphometric findings in predicting an ADHD
diagnosis was sufficient, which indicates that MRI-based assessments are a
promising strategy for the development of a biomarker.
PMID- 28406943
TI - Defective enamel and bone development in sodium-dependent citrate transporter
(NaCT) Slc13a5 deficient mice.
AB - There has been growing recognition of the essential roles of citrate in
biomechanical properties of mineralized tissues, including teeth and bone.
However, the sources of citrate in these tissues have not been well defined, and
the contribution of citrate to the regulation of odontogenesis and osteogenesis
has not been examined. Here, tooth and bone phenotypes were examined in sodium
dependent citrate transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 and 32
weeks of age. Slc13a5 deficiency led to defective tooth development,
characterized by absence of mature enamel, formation of aberrant enamel matrix,
and dysplasia and hyperplasia of the enamel organ epithelium that progressed with
age. These abnormalities were associated with fragile teeth with a possible
predisposition to tooth abscesses. The lack of mature enamel was consistent with
amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone
mineral density and impaired bone formation in 13-week-old mice but not in older
mice. The findings revealed the potentially important role of citrate and Slc13a5
in the development and function of teeth and bone.
PMID- 28406945
TI - Predicting 3D lip shapes using facial surface EMG.
AB - AIM: The aim of this study is to prove that facial surface electromyography
(sEMG) conveys sufficient information to predict 3D lip shapes. High sEMG
predictive accuracy implies we could train a neural control model for activation
of biomechanical models by simultaneously recording sEMG signals and their
associated motions. MATERIALS AND METHODS: With a stereo camera set-up, we
recorded 3D lip shapes and simultaneously performed sEMG measurements of the
facial muscles, applying principal component analysis (PCA) and a modified
general regression neural network (GRNN) to link the sEMG measurements to 3D lip
shapes. To test reproducibility, we conducted our experiment on five volunteers,
evaluating several sEMG features and window lengths in unipolar and bipolar
configurations in search of the optimal settings for facial sEMG. CONCLUSIONS:
The errors of the two methods were comparable. We managed to predict 3D lip
shapes with a mean accuracy of 2.76 mm when using the PCA method and 2.78 mm when
using modified GRNN. Whereas performance improved with shorter window lengths,
feature type and configuration had little influence.
PMID- 28406944
TI - Fixational saccades are more disconjugate in adults than in children.
AB - PURPOSE: Fixational eye movements are of particular interest for three reasons.
They are critical for preventing visual fading and enhancing visual perception;
their disconjugacy allows scanning in three dimensions, and their neural
correlates span through the cortico-striatal, striato-collicular and brainstem
networks. Fixational eye movements are altered in various pediatric
ophthalmologic and neurologic disorders. The goal of this study was to compare
the dynamics of fixational eye movements in normal children and adults. METHODS:
We measured the fixational saccades and inter-saccadic drifts in eye positions
using infrared video-oculography in children and adults. We assessed the
frequency, amplitude, main-sequence, and disconjugacy of fixational saccades as
well as the intra-saccadic drift velocity and variance between these two groups.
RESULTS: We found a similar frequency but an increase in the amplitude of
fixational saccades in children compared to adults. We also found that the
fixational saccades were more conjugate in children than in adults. The inter
saccadic drifts were comparable between the two groups. DISCUSSION: This study
provides normative values of dynamics of fixational eye movement in children and
adults. The greater disconjugacy of fixational saccades in adults suggests the
existence of neural mechanisms that can independently regulate the movements of
two eyes. The differences between adult and pediatric populations could be due to
completion of the development of binocularly independent regulation of fixational
saccades nearing adulthood. The alternate possibility is that the increased
disconjugacy between the two eyes may represent a deficiency in the eye movement
performance as a function of increasing age.
PMID- 28406946
TI - Cholera returns to southern Vietnam in an outbreak associated with consuming
unsafe water through iced tea: A matched case-control study.
AB - BACKGROUND: After more than a decade of steadily declining notifications, the
number of reported cholera cases has recently increased in Vietnam. We conducted
a matched case-control study to investigate transmission of cholera during an
outbreak in Ben Tre, southern Vietnam, and to explore the associated risk
factors. METHODOLOGY/PRINCIPAL FINDINGS: Sixty of 71 diarrheal patients confirmed
to be infected with cholera by culture and diagnosed between May 9 and August 3,
2010 in Ben Tre were consecutively recruited as case-patients. Case-patients were
matched 1:4 to controls by commune, sex, and 5-year age group. Risk factors for
cholera were examined by multivariable conditional logistic regression. In
addition, environmental samples from villages containing case-patients were taken
to identify contamination of food and water sources. The regression indicated
that drinking iced tea (adjusted odds ratio (aOR) = 8.40, 95% confidence interval
(CI): 1.84-39.25), not always boiling drinking water (aOR = 2.62, 95% CI: 1.03
6.67), having the main source of water for use being close to a toilet (aOR =
4.36, 95% CI: 1.37-13.88), living with people who had acute diarrhea (aOR =
13.72, 95% CI: 2.77-67.97), and little or no education (aOR = 4.89, 95% CI: 1.18
20.19) were significantly associated with increased risk of cholera. In contrast,
drinking stored rainwater (aOR = 0.17, 95% CI: 0.04-0.63), eating cooked seafood
(aOR = 0.27, 95% CI: 0.10-0.73), and eating steamed vegetables (aOR = 0.22, 95%
CI: 0.07-0.70) were protective against cholera. Vibrio cholerae O1 Ogawa carrying
ctxA was found in two of twenty-five river water samples and one of six
wastewater samples. CONCLUSIONS/SIGNIFICANCE: The magnitude of the cholera
outbreak in Ben Tre was lower than in other similar settings. This investigation
identified several risk factors and underscored the importance of continued
responses targeting cholera prevention in southern Vietnam. The association
between drinking iced tea and cholera and the spread of V. cholerae O1, altered
El Tor strains warrant further research. These findings might be affected by a
number of limitations due to the inability to capture asymptomatic or mildly
symptomatic infections, the possible underreporting of personal unhygienic
behaviors, and the purposive selection of environmental samples.
PMID- 28406948
TI - QuickLib, a method for building fully synthetic plasmid libraries by seamless
cloning of degenerate oligonucleotides.
AB - Incorporation of synthetic degenerate oligonucleotides into plasmids for building
highly diverse genetic libraries requires efficient and quantitative DNA
manipulation. We present a fast and seamless method for generating libraries of
PCR-synthesized plasmids designed with a degenerate sequence and short
overlapping ends. Our method called QuickLib should find many applications in
synthetic biology; as an example, we easily prepared genetic libraries of
Escherichia coli expressing billions of different backbone cyclic peptides.
PMID- 28406947
TI - Prevalence of hepatitis C virus in adult population in the Czech Republic - time
for birth cohort screening.
AB - Chronic hepatitis C is curable disease. Low detection rate could be one of the
reasons of poor treatment uptake. It is important to identify HCV prevalence and
anti-hepatitis C virus (HCV) positive patients in population by effective
screening strategy such as risk-based or birth cohort screening programs. There
are no national population-based estimates of the HCV prevalence in the Czech
Republic (CZ). The most recent seroprevalence survey determined a prevalence of
positive anti-HCV antibodies of 0.2% (in 2001). The aim of the study was to
determine the seroprevalence of HCV, HCV viraemia and HCV genotype in the CZ
adult population. We also estimated the number of persons living with chronic
hepatitis C in CZ. The examined group included 3000 adults, 18-90 years of age
enrolled in 2015. All serum samples were examined to determined anti-HCV
antibodies positivity, HCV-RNA positivity and genotypes. Of the 3000 samples, 50
were found to be anti-HCV-positive, for a seroprevalence of 1.67% (2.39% in
males, 0.98% in females). The overall prevalence of positive HCV RNA was 0.93%:
1.5% in males, 0.39% in females. HCV genotype (GT) 1a was determined in 25%, GT
1b in 25% and GT 3a in 46%. Since 2001, the HCV seroprevalence has increased 8
fold. The highest HCV seroprevalence occurred in males aged 30-44 years. We can
estimate that there are more than 140,000 people with HCV antibodies and more
than 80,000 people with chronic hepatitis C living in the CZ. The introduction of
birth cohort HCV screening could be beneficial for the country.
PMID- 28406949
TI - Antimicrobial-resistant infections among postpartum women at a Ugandan referral
hospital.
AB - INTRODUCTION: Puerperal sepsis causes 10% of maternal deaths in Africa, but
prospective studies on incidence, microbiology and antimicrobial resistance are
lacking. METHODS: We performed a prospective cohort study of 4,231 Ugandan women
presenting to a regional referral hospital for delivery or postpartum care,
measured vital signs after delivery, performed structured physical exam, symptom
questionnaire, and microbiologic evaluation of febrile and hypothermic women.
Malaria rapid diagnostic testing, blood and urine cultures were performed
aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial
susceptibility and breakpoints were determined using disk diffusion per EUCAST
standards. Hospital diagnoses, treatments and outcomes were abstracted from
patient charts. RESULTS: Mean age was 25 years, 12% were HIV-infected, and 50%
had cesarean deliveries. Approximately 5% (205/4176) with >=1 temperature
measurement recorded developed postpartum fever or hypothermia; blood and urine
samples were collected from 174 (85%), and 17 others were evaluated clinically.
Eighty-four (48%) had at least one confirmed source of infection: 39% (76/193)
clinical postpartum endometritis, 14% (25/174) urinary tract infection (UTI), 3%
(5/174) bloodstream infection. Another 3% (5/174) had malaria. Overall, 30/174
(17%) had positive blood or urine cultures, and Acinetobacter species were the
most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80%) were
multidrug-resistant and cefepime non-susceptible. CONCLUSIONS: For women in rural
Uganda with postpartum fever, we found a high rate of antibiotic resistance among
cultured urinary and bloodstream infections, including cephalosporin-resistant
Acinetobacter species. Increasing availability of microbiology testing to inform
appropriate antibiotic use, development of antimicrobial stewardship programs,
and strengthening infection control practices should be high priorities.
PMID- 28406950
TI - Interaction of iron status with single nucleotide polymorphisms on incidence of
type 2 diabetes.
AB - The objective of this study is to find single nucleotide polymorphisms (SNPs)
associated with a risk of Type 2 diabetes (T2D) in Korean adults and to
investigate the longitudinal association between these SNPs and T2D and the
interaction effects of iron intake and average hemoglobin level. Data from the
KoGES_Ansan and Ansung Study were used. Gene-iron interaction analysis was
conducted using a two-step approach. To select candidate SNPs associated with
T2D, a total of 7,935 adults at baseline were included in genome-wide association
analysis (step one). After excluding T2D prevalent cases, prospective analyses
were conducted with 7,024 adults aged 40-69 (step two). The association of
selected SNPs and iron status with T2D and their interaction were determined
using a Cox proportional hazard model. A total of 3 SNPs [rs9465871 (CDKAL1),
rs10761745 (JMJD1C), and rs163177 (KCNQ1)] were selected as candidate SNPs
related to T2D. Among them, rs10761745 (JMJD1C) and rs163177 (KCNQ1) were
prospectively associated with T2D. High iron intake was also prospectively
associated with the risk of T2D after adjusting for covariates. Average
hemoglobin level was positively associated with T2D after adjusting for
covariates in women. We also found significant interaction effects between
rs10761745 (JMJD1C) and average hemoglobin levels on the risk of T2D among women
with normal inflammation and without anemia at baseline. In conclusion, KCNQ1 and
JMJD1C may prospectively contribute to the risk of T2D incidence among adults
over the age of 40 and JMJD1C, but CDKAL1 may not, and iron status may
interactively contribute to T2D incidence in women.
PMID- 28406951
TI - Protection induced by virus-like particles containing Toxoplasma gondii microneme
protein 8 against highly virulent RH strain of Toxoplasma gondii infection.
AB - Toxoplasma gondii (T. gondii) microneme protein 8 (MIC8) represents a novel,
functional distinct invasion factor. In this study, we generated virus-like
particles (VLPs) targeting Toxoplasma gondii MIC8 for the first time, and
investigated the protection against highly virulent RH strain of T. gondii in a
mouse model. We found that VLP vaccination induced Toxoplasma gondii-specific IgG
and IgG1 antibody responses in the sera. Upon challenge infection with RH strain
of T. gondii tachyzoites, vaccinated mice showed a significant increase of both
IgG antibodies in sera and IgA antibodies in feces compared to those before
challenge, and a rapid expansion of both germinal center B cell (B220+, GL7+) and
T cell (CD4+, CD8+) populations. Importantly, intranasally immunized mice showed
higher neutralizing antibodies and displayed no proinflammatory cytokine IFN
gamma in the spleen. Mice were completely protected from a lethal challenge
infection with the highly virulent T. gondii (RH) showing no body weight loss
(100% survival). Our study shows the effective protection against T. gondii
infection provided by VLPs containing microneme protein 8 of T. gondii, thus
indicating a potential T. gondii vaccine candidate.
PMID- 28406952
TI - Individual and contextual factors associated with appropriate healthcare seeking
behavior among febrile children in Tanzania.
AB - INTRODUCTION: Fever in malaria endemic areas, has been shown to strongly predict
malaria infection and is a key symptom influencing malaria treatment. WHO
recommended confirmation testing for Plasmodium spp. before initiation of
antimalarials due to increased evidence of the decrease of morbidity and
mortality from malaria, decreased malaria associated fever, and increased
evidence of high prevalence of non-malaria fever. To immediately diagnose and
promptly offer appropriate management, caretakers of children with fever should
seek care where these services can be offered; in health facilities. OBJECTIVES:
This study was conducted to describe healthcare seeking behaviors among
caretakers of febrile under five years, in Tanzania. And to determine children's,
household and community-level factors associated with parents' healthcare seeking
behavior in health facilities. METHODS: Secondary data analysis was done using
the Tanzania HIV and Malaria Indicator Surveys (THMIS) 2011-2012. Three-level
mixed effects logistic regression was used to assess children's, household and
community-level factors associated with appropriate healthcare seeking behavior
among care takers of febrile children as well as differentiating between
household and community variabilities. RESULTS: Of the 8573 children under the
age of five years surveyed, 1,675(19.5%) had a history of fever two weeks
preceding the survey. Of these, 951 (56.8%) sought appropriate healthcare.
Febrile children aged less than a year have 2.7 times higher odds of being taken
to the health facilities compared to children with two or more years of age. (OR:
2.7; 95%CI: 1.50-4.88). Febrile children from households headed by female
caretakers have almost three times higher odds of being taken to the health
facilities (OR: 2.85; 95%CI; 1.41-5.74) compared to households headed by men.
Febrile children with caretakers exposed to mass media (radio, television and
newspaper) have more than two times higher odds of being taken to health
facilities compared to those not exposed to mass media. Febrile children from
regions with malaria prevalence above national level have 41% less odds of being
taken to health facilities (OR: 0.49; 95%CI: 0.29-0.84) compared to those febrile
children coming from areas with malaria prevalence below the national level.
Furthermore, febrile children coming from areas with higher community education
levels have 57% (OR: 1.57; 95%CI: 1.14-2.15) higher odds of being taken to health
facilities compared to their counterparts coming from areas with low levels of
community education. CONCLUSION AND RECOMMENDATION: To effectively and
appropriately manage and control febrile illnesses, the low proportion of febrile
children taken to health facilities by their caretakers should be addressed
through frequent advocacy of the importance of appropriate healthcare seeking
behavior, using mass media particularly in areas with high malaria prevalence.
Multifaceted approach needs to be used in malaria control and eradication as
multiple factors are associated with appropriate healthcare seeking behavior.
PMID- 28406953
TI - Human behavioral complexity peaks at age 25.
AB - Random Item Generation tasks (RIG) are commonly used to assess high cognitive
abilities such as inhibition or sustained attention. They also draw upon our
approximate sense of complexity. A detrimental effect of aging on pseudo-random
productions has been demonstrated for some tasks, but little is as yet known
about the developmental curve of cognitive complexity over the lifespan. We
investigate the complexity trajectory across the lifespan of human responses to
five common RIG tasks, using a large sample (n = 3429). Our main finding is that
the developmental curve of the estimated algorithmic complexity of responses is
similar to what may be expected of a measure of higher cognitive abilities, with
a performance peak around 25 and a decline starting around 60, suggesting that
RIG tasks yield good estimates of such cognitive abilities. Our study illustrates
that very short strings of, i.e., 10 items, are sufficient to have their
complexity reliably estimated and to allow the documentation of an age-dependent
decline in the approximate sense of complexity.
PMID- 28406955
TI - Predictive long-range allele-specific mapping of regulatory variants and target
transcripts.
AB - Genome-wide association studies (GWASs) have identified a large number of
noncoding associations, calling for systematic mapping to causal regulatory
variants and their distal target genes. A widely used method, quantitative trait
loci (QTL) mapping for chromatin or expression traits, suffers from sample-to
sample experimental variation and trans-acting or environmental effects. Instead,
alleles at heterozygous loci can be compared within a sample, thereby controlling
for those confounding factors. Here we introduce a method for chromatin structure
based allele-specific pairing of regulatory variants and target transcripts. With
phased genotypes, much of allele-specific expression could be explained by paired
allelic cis-regulation across a long range. This approach showed approximately
two times greater sensitivity than QTL mapping. There are cases in which allele
imbalance cannot be tested because heterozygotes are not available among
reference samples. Therefore, we employed a machine learning method to predict
missing positive cases based on various features shared by observed allele
specific pairs. We showed that only 10 reference samples are sufficient to
achieve high prediction accuracy with a low sampling variation. In conclusion,
our method enables highly sensitive fine mapping and target identification for
trait-associated variants based on a small number of reference samples.
PMID- 28406954
TI - Therapeutic efficacy of intra-articular hyaluronan derivative and platelet-rich
plasma in mice following axial tibial loading.
AB - OBJECTIVE: To investigate the therapeutic potential of intra-articular hyaluronan
derivative HYADD(r) 4-G and/or platelet-rich plasma (PRP) in a mouse model of non
invasive joint injury. METHODS: Non-invasive axial tibial loading was used to
induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a
single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD(r) 4
G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after
loading with or without PRP. Phosphate-buffered-saline was injected as control.
Knee joints were harvested at 5 or 56 days post-loading and prepared for micro
computed tomography scanning and subsequently processed for histology.
Immunostaining was performed for aggrecan to monitor its distribution, for CD44
to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix
protein) as an index for cartilage matrix changes related to loading and
cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis.
RESULTS: Loading initiated cartilage proteoglycan loss and chondrocyte apoptosis
within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage
degeneration, but increased synovitis and ectopic calcification after 9N loading)
at 56 days. Mice treated with repeated HYADD(r) 4-G (15 mg/mL) or HYADD(r) 4-G (8
mg/mL) +/- PRP or PRP alone exhibited no significant improvement in the short
term (5 days) and long-term (56 days) consequences of joint loading except for a
trend for improved bone changes compared to non-loaded joints. CONCLUSION: While
we failed to show an overall effect of intra-articular delivery of hyaluronan
derivative and/or PRP in reversing/protecting the pathological events in
cartilage and synovium following joint injury, some bone alterations were
relatively less severe with hyaluronan-derivative at higher concentration or in
association with PRP.
PMID- 28406956
TI - Genetic diversity and variation of Chinese fir from Fujian province and Taiwan,
China, based on ISSR markers.
AB - Genetic diversity and variation among 11 populations of Chinese fir from Fujian
province and Taiwan were assessed using inter-simple sequence repeat (ISSR)
markers to reveal the evolutionary relationship in their distribution range in
this report. Analysis of genetic parameters of the different populations showed
that populations in Fujian province exhibited a greater level of genetic
diversity than did the populations in Taiwan. Compared to Taiwan populations,
significant limited gene flow were observed among Fujian populations. An UPGMA
cluster analysis showed that the most individuals of Taiwan populations formed a
single cluster, whereas 6 discrete clusters were formed by each population from
Fujian. All populations were divided into 3 main groups and that all 5
populations from Taiwan were gathered into a subgroup combined with 2
populations, Dehua and Liancheng, formed one of the 3 main groups, which
indicated relative stronger relatedness. It is supported by a genetic structure
analysis. All those results are suggesting different levels of genetic diversity
and variation of Chinese fir between Fujian and Taiwan, and indicating different
patterns of evolutionary process and local environmental adaption.
PMID- 28406957
TI - Event-related potentials to changes in facial expression in two-phase
transitions.
AB - The purpose of the study was to compare event-related potentials (ERPs) to
different transitions between emotional and neutral facial expressions. The
stimuli contained a single transition between two different images of the same
face, giving a strong impression of changing expression though apparent motion
whilst eliminating change in irrelevant stimulus variables such as image contrast
or identity. Stimuli were calibrated for intensity, valence and perceived emotion
category and only trials where the target emotion was correctly identified were
included. In the first experiment, a magnification change (zoom) was a control
condition. Transitions from neutral to angry expressions produced a more negative
N1 with longer peak latency, and more positive P2 than did an increase in
magnification. Critically, response to neutral following angry, relative to
neutral following magnified, showed a generally more negative ERP with a delayed
N1 peak and reduced P2 amplitude. In the second experiment, comparison of neutral
happy and neutral-frightened transitions showed significantly different ERPs to
emotional expression change. Responses to the reversed direction of a transition
(happy-neutral and frightened-neutral) were much reduced. Unlike the comparison
of angry-neutral with magnified-neutral, there were minimal differences in the
responses to neutral following happy and neutral following frightened. The
results demonstrate in a young adult sample the directionality of responses to
facial expression dynamics, and suggest a separation of neural mechanisms for
detecting expression changes and magnification changes.
PMID- 28406958
TI - Molecular analysis of Culex quinquefasciatus larvae responses to Lysinibacillus
sphaericus Bin toxin.
AB - Lysinibacillus sphaericus produces the mosquito larvicidal binary toxin
consisting of BinA and BinB, which are both required for toxicity against Culex
and Anopheles larvae. The molecular mechanisms behind Bin toxin-induced damage
remain unexplored. We used whole-genome microarray-based transcriptome analysis
to better understand how Culex larvae respond to Bin toxin treatment at the
molecular level. Our analyses of Culex quinquefasciatus larvae transcriptome
changes at 6, 12, and 18 h after Bin toxin treatment revealed a wide range of
transcript signatures, including genes linked to the cytoskeleton, metabolism,
immunity, and cellular stress, with a greater number of down-regulated genes than
up-regulated genes. Bin toxin appears to mainly repress the expression of genes
involved in metabolism, the mitochondrial electron transport chain, and the
protein transporter of the outer/inner mitochondrial membrane. The induced genes
encode proteins linked to mitochondrial-mediated apoptosis and cellular
detoxification including autophagic processes and lysosomal compartments. This
study is, to our knowledge, the first microarray analysis of Bin toxin-induced
transcriptional responses in Culex larvae, providing a basis for an in-depth
understanding of the molecular nature of Bin toxin-induced damage.
PMID- 28406959
TI - Enhancement of immune cytokines and splenic CD4+ T cells by electroacupuncture at
ST36 acupoint of SD rats.
AB - Electroacupuncture at the ST36 acupoint can enhance the body's immune function.
However, the mechanism for this enhancement has not been fully described. Our
study was designed to investigate the effect of electroacupuncture on the immune
function of Sprague-Dawley (SD) rats. The rats were randomly divided into three
groups: a control group, a non-acupoint group (abdominal muscle acupuntured) and
a ST36 acupoint group. Our results showed that successive electroacupuncture at
the ST36 acupoint for 3 d significantly enhanced the interferon-gamma (IFN-gamma)
level in the serum of SD rats. The results also showed that the serum and
extracts from spleen cells of the ST36 acupoint group contained higher levels of
interleukin (IL)-2 and IL-17 compared to those of the other two groups.
Immunohistochemical analysis showed that electroacupuncture applied to the ST36
acupoint enhanced the expression level of CD4 in spleen cells. Furthermore, it
was observed that CD4 co-localized with transient receptor potential vanilloid
(TRPV) channels at the membrane of splenic CD4+ T cells and the expression level
of CD4 was related to TRPV channels in the electroacupuncture treatment. These
observations indicated that electroacupuncture stimulation at the ST36 acupoint
enhanced the level of immune cytokines and splenic CD4+ T cells through TRPV
channels in this system.
PMID- 28406960
TI - Translation and validation of the Serbian primary biliary cholangitis-40
questionnaire.
AB - BACKGROUND AND AIMS: To translate into Serbian and validate the Primary Biliary
Cholangitis-40 (PBC-40) and PBC-27 questionnaires. MATERIALS AND METHODS: Ninety
four consecutive outpatients with the diagnosis of PBC from three departments
across two tertiary care institutions in Belgrade were enrolled from February to
October 2016. Standard methodology for cultural adaption of healthcare related
quality of life questionnaires was used, and included: a forward translation,
backward translation and a pilot test of the Serbian PBC-40 on five patients who
gave suggestions and comments. For evaluation of the questionnaires, acceptance
was shown by the proportion of missing items and the internal consistency was
assessed using Cronbach's alpha coefficient. The PBC-40 was self-administered
under the supervision of an experienced hepatologist. The PBC-27 is a shorter
version of the PBC-40. RESULTS: A total of 92 (97.9%) of the patients were
females. The mean age was 59.26 +/- 1.05 years and the average length of disease
was 60.45 +/- 48.314 months. The average PBC-40 score was 85.62 +/- 30.46. The
total time needed to complete the questionnaire ranged from 7 to 16 minutes. The
proportion of missing items was 5.45% (205/3760). Cronbach's alpha for the entire
scale was 0.93. Reliability for all of the domains of the PBC-40 was above 0.70,
except for the domain "Symptoms" (alpha = 0.52). Overall reliability of the PBC
27 was alpha = 0.90. Domains "Dryness", "Symptoms" and "Fatigue" demonstrated
reliability below alpha = 0.70. CONCLUSIONS: The Serbian PBC-40 is a valid and
reasonably adequate for use in Serbian PBC patients. The PBC-40 is preferred over
the PBC-27.
PMID- 28406961
TI - Pharmacogenetic variants in TPMT alter cellular responses to cisplatin in inner
ear cell lines.
AB - Cisplatin is a highly-effective and widely-used chemotherapeutic agent that
causes ototoxicity in many patients. Pharmacogenomic studies of key genes
controlling drug biotransformation identified variants in thiopurine
methyltransferase (TPMT) as predictors of cisplatin-induced ototoxicity, although
the mechanistic basis of this interaction has not been reported. Expression
constructs of TPMT*3A, *3B and *3C variants were generated and monitored in
cultured cells. Cellular TPMT*3A levels were detected at >20-fold lower amounts
than the wild type confirming the unstable nature of this variant. The expression
of wild type TPMT (TPMT*1) in two murine ear cell lines, HEI-OC1 and UB/OC-1,
significantly mitigated their susceptibility to cisplatin toxicity. Cisplatin
treatment induced Tlr4 gene expression in HEI-OC1 cells and this response was
blunted by the expression of wild type TPMT but not TPMT*3A. In line with the
significant mitigation of TPMT*1-expressing cells to cisplatin cytotoxicity,
these findings demonstrate a drug-gene interaction between increased TPMT
activity and decreased susceptibility to cisplatin-induced toxicity of inner ear
cells.
PMID- 28406962
TI - Ethnic differences in association of high body mass index with early onset of
Type 1 diabetes - Arab ethnicity as case study.
AB - OBJECTIVE: The "accelerator hypothesis" predicts early onset of Type 1 diabetes
(T1D) in heavier children. Studies testing direction of correlation between body
mass index (BMI) and age at onset of T1D in different continental populations
have reported differing results-inverse, direct, and neutral. Evaluating the
correlation in diverse ethnic populations is required to generalize the
accelerator hypothesis. METHODS: The study cohort comprised 474 Kuwaiti children
of Arab ethnicity diagnosed with T1D at age 6 to 18 years during 2011-2013. Age-
and sex-adjusted BMI z-scores were calculated by comparing the BMI measured at
diagnosis with Kuwaiti pediatric population reference data recorded during
comparable time-period. Multiple linear regression and Pearson correlation
analyses were performed. RESULTS: BMI z-score was seen inversely associated with
onset age (r,-0.28; p-value<0.001). Children with BMI z-score>0 (i.e. BMI
>national average) showed a stronger correlation (r,-0.38; p-value<0.001) than
those with BMI z-score<0 (r,-0.19; p-value<0.001); the former group showed
significantly lower mean onset age than the latter group (9.6+/-2.4 versus 10.5+/
2.7; p-value<0.001). Observed inverse correlation was consistent with that seen
in Anglo-saxon, central european, caucasian, and white children while
inconsistent with that seen in Indian, New Zealander, and Australian children.
CONCLUSIONS: The accelerator hypothesis generalizes in Arab pediatric population
from Kuwait.
PMID- 28406963
TI - Historical and ecological drivers of the spatial pattern of Chondrichthyes
species richness in the Mediterranean Sea.
AB - Chondrichthyes, which include Elasmobranchii (sharks and batoids) and Holocephali
(chimaeras), are a relatively small group in the Mediterranean Sea (89 species)
playing a key role in the ecosystems where they are found. At present, many
species of this group are threatened as a result of anthropogenic effects,
including fishing activity. Knowledge of the spatial distribution of these
species is of great importance to understand their ecological role and for the
efficient management of their populations, particularly if affected by fisheries.
This study aims to analyze the spatial patterns of the distribution of
Chondrichthyes species richness in the Mediterranean Sea. Information provided by
the studied countries was used to model geographical and ecological variables
affecting the Chondrichthyes species richness. The species were distributed in 16
Operational Geographical Units (OGUs), derived from the Geographical Sub-Areas
(GSA) adopted by the General Fisheries Commission of the Mediterranean Sea
(GFCM). Regression analyses with the species richness as a target variable were
adjusted with a set of environmental and geographical variables, being the model
that links richness of Chondrichthyes species with distance to the Strait of
Gibraltar and number of taxonomic families of bony fishes the one that best
explains it. This suggests that both historical and ecological factors affect the
current distribution of Chondrichthyes within the Mediterranean Sea.
PMID- 28406964
TI - Granulocyte colony stimulating factor therapy for stroke: A pairwise meta
analysis of randomized controlled trial.
AB - Granulocyte colony-stimulating factor (G-CSF) is atherapeutic candidate for
stroke that has demonstrated anti-inflammatory and neuroprotective properties.
Data from preclinical and clinical studies have suggested the safety and efficacy
of G-CSF in stroke; however, the exact effects and utility of this cytokine in
patients remain disputed. We performed a meta-analysis of randomized controlled
trials of G-CSF in ischemic and hemorrhagic stroke to assess its clinical safety
and efficacy. Electronic databases were searched for relevant publications in
English and Chinese. A total of 14 trials met the inclusion criteria. G-CSF
(cumulative dose range, 1-135MUg/kg/day) was tested against placebo in a total of
1037 participants. There was no difference in the rate of mortality between
groups (odds ratio, 1.23; 95% confidence interval, 0.76-1.97, p = 0.40).
Moreover, the rate of serious adverse events did not differ between groups and
provided evidence for the safety of G-CSF administration in stroke patients (odds
ratio, 1.11; 95% confidence interval, 0.77-1.61, p = 0.57). No significant
outcome benefits were noted with respect to the National Institutes of Health
Stroke Scale (mean difference, -0.16; 95% confidence interval, -1.02-0.70, p =
0.72); however, improvements were noted with respect to the Barthel Index (mean
difference, 8.65; 95% confidence interval 0.98-16.32; p = 0.03). In conclusion,
it appears to be safe in administration of G-CSF, but it will increase leukocyte
count. G-CSF was weakly significant benefit with improving the BI scores, while
there was no improvement in the NIHSS scores. Larger and more robustly designed
trials of G-CSF in stroke are needed to confirm the results.
PMID- 28406965
TI - Palaeolake isolation and biogeographical process of freshwater fishes in the
Yellow River.
AB - The Yellow River, one of the very few in the Earth, originated from many
dispersive palaeolakes. Taking this unique advantage, we examined the roles of
palaeolake isolation vs. geological processes vs. climate in determining current
fish biogeographic pattern. We reviewed available data on fish species and their
geographical distribution in the river, as well as palaeolake development,
geological and climatic parameters. The 138 fish species recorded in the river
could be divided into 8 biogeographic regions, corresponding to the distribution
of palaeolakes and respective endemic species. Through variation partitioning
analysis, palaeolake isolation was the most influential factor explaining 43.6%
of the total variance on the current fish distribution. The Quaternary Ice Age
produced a transitional distribution for fishes from the glacier to warm water,
especially for the subfamily Schizothoracinae, which showed various degrees of
specialisation along altitudes. We suggested that fish biogeography in the Yellow
river was basically shaped by palaeolake isolation, and further carved under
serials of geologic events and contemporary climate change.
PMID- 28406966
TI - Continuous uniformly finite time exact disturbance observer based control for
fixed-time stabilization of nonlinear systems with mismatched disturbances.
AB - This paper presents a continuous composite control scheme to achieve fixed-time
stabilization for nonlinear systems with mismatched disturbances. The composite
controller is constructed in two steps: First, uniformly finite time exact
disturbance observers are proposed to estimate and compensate the disturbances.
Then, based on adding a power integrator technique and fixed-time stability
theory, continuous fixed-time stable state feedback controller and Lyapunov
functions are constructed to achieve global fixed-time system stabilization. The
proposed control method extends the existing fixed-time stable control results to
high order nonlinear systems with mismatched disturbances and achieves global
fixed-time system stabilization. Besides, the proposed control scheme improves
the disturbance rejection performance and achieves performance recovery of
nominal system. Simulation results are provided to show the effectiveness, the
superiority and the applicability of the proposed control scheme.
PMID- 28406967
TI - Differential transcriptome analysis supports Rhodnius montenegrensis and Rhodnius
robustus (Hemiptera, Reduviidae, Triatominae) as distinct species.
AB - Chagas disease is one of the main parasitic diseases found in Latin America and
it is estimated that between six and seven million people are infected worldwide.
Its etiologic agent, the protozoan Trypanosoma cruzi, is transmitted by
triatomines, some of which from the genus Rhodnius. Twenty species are currently
recognized in this genus, including some closely related species with low levels
of morphological differentiation, such as Rhodnius montenegrensis and Rhodnius
robustus. In order to investigate genetic differences between these two species,
we generated large-scale RNA-sequencing data (consisting of four RNA-seq
libraries) from the heads and salivary glands of males of R. montenegrensis and
R. robustus. Transcriptome assemblies produced for each species resulted in
64,952 contigs for R. montenegrensis and 70,894 contigs for R. robustus, with N50
of approximately 2,100 for both species. SNP calling based on the more complete
R. robustus assembly revealed 3,055 fixed interspecific differences and 216
transcripts with high levels of divergence which contained only fixed differences
between the two species. A gene ontology enrichment analysis revealed that these
highly differentiated transcripts were enriched for eight GO terms related to AP
2 adaptor complex, as well as other interesting genes that could be involved in
their differentiation. The results show that R. montenegrensis and R. robustus
have a substantial quantity of fixed interspecific polymorphisms, which suggests
a high degree of genetic divergence between the two species and likely
corroborates the species status of R. montenegrensis.
PMID- 28406968
TI - The sense of balance in humans: Structural features of otoconia and their
response to linear acceleration.
AB - We explored the functional role of individual otoconia within the otolith system
of mammalians responsible for the detection of linear accelerations and head
tilts in relation to the gravity vector. Details of the inner structure and the
shape of intact human and artificial otoconia were studied using environmental
scanning electron microscopy (ESEM), including decalcification by
ethylenediaminetetraacetic acid (EDTA) to discriminate local calcium carbonate
density. Considerable differences between the rhombohedral faces of human and
artificial otoconia already indicate that the inner architecture of otoconia is
not consistent with the point group -3m. This is clearly confirmed by decalcified
otoconia specimen which are characterized by a non-centrosymmetric volume
distribution of the compact 3+3 branches. This structural evidence for asymmetric
mass distribution was further supported by light microscopy in combination with a
high speed camera showing the movement of single otoconia specimen (artificial
specimen) under gravitational influence within a viscous medium (artificial
endolymph). Moreover, the response of otoconia to linear acceleration forces was
investigated by particle dynamics simulations. Both, time-resolved microscopy and
computer simulations of otoconia acceleration show that the dislocation of
otoconia include significant rotational movement stemming from density asymmetry.
Based on these findings, we suggest an otolith membrane expansion/stiffening
mechanism for enhanced response to linear acceleration transmitted to the
vestibular hair cells.
PMID- 28406970
TI - Correction: Comparison of 18F-FDG PET/CT and DWI for detection of mediastinal
nodal metastasis in non-small cell lung cancer: A meta-analysis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173104.].
PMID- 28406969
TI - Reconstruction of 3D structures of MET antibodies from electron microscopy 2D
class averages.
AB - Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4) and the IgG4-MET
antigen complex was investigated by creating their atomic models with an
integrative experimental and computational approach. In particular, we used two
dimensional (2D) Electron Microscopy (EM) images, image class averaging, homology
modeling, Rapidly exploring Random Tree (RRT) structure sampling, and fitting of
models to images, to find the relative orientations of antibody domains that are
consistent with the EM images. We revealed that the conformational preferences of
the constructs depend on the extent of the hinge flexibility. We also quantified
how the MET antigen impacts on the conformational dynamics of IgG4. These
observations allow to create testable hypothesis to investigate MET biology. Our
protocol may also help describe structural diversity of other antigen systems at
approximately 5 A precision, as quantified by Root-Mean-Square Deviation (RMSD)
among good-scoring models.
PMID- 28406971
TI - Association between physicians' interaction with pharmaceutical companies and
their clinical practices: A systematic review and meta-analysis.
AB - BACKGROUND: Pharmaceutical company representatives likely influence the
prescribing habits and professional behaviors of physicians. The objective of
this study was to systematically review the association between physicians'
interactions with pharmaceutical companies and their clinical practices. METHODS:
We used the standard systematic review methodology. Observational and
experimental study designs examining any type of targeted interaction between
practicing physicians and pharmaceutical companies were eligible. The search
strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two
reviewers selected studies, abstracted data, and assessed risk of bias in
duplicate and independently. We assessed the quality of evidence using the GRADE
approach. RESULTS: Twenty articles reporting on 19 studies met our inclusion
criteria. All of these studies were conducted in high-income countries and
examined different types of interactions, including detailing, industry-funded
continuing medical education, and receiving free gifts. While all included
studies assessed prescribing behaviors, four studies also assessed financial
outcomes, one assessed physicians' knowledge, and one assessed their beliefs.
None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a
consistent association between interactions promoting a medication, and
inappropriately increased prescribing rates, lower prescribing quality, and/or
increased prescribing costs. The remaining four studies found both associations
and lack of significant associations for the different types of exposures and
drugs examined in the studies. A meta-analysis of six of these studies found a
statistically significant association between exposure and physicians'
prescribing behaviors (OR = 2.52; 95% CI 1.82-3.50). The quality of evidence was
downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis
excluding studies at high risk of bias did not substantially change these
results. A subgroup analysis did not find a difference by type of exposure.
CONCLUSION: There is moderate quality evidence that physicians' interactions with
pharmaceutical companies are associated with their prescribing patterns and
quality.
PMID- 28406972
TI - Disruption of outer blood-retinal barrier by Toxoplasma gondii-infected monocytes
is mediated by paracrinely activated FAK signaling.
AB - Ocular toxoplasmosis is mediated by monocytes infected with Toxoplasma gondii
that are disseminated to target organs. Although infected monocytes can easily
access to outer blood-retinal barrier due to leaky choroidal vasculatures, not
much is known about the effect of T. gondii-infected monocytes on outer blood
retinal barrier. We prepared human monocytes, THP-1, infected with T. gondii and
human retinal pigment epithelial cells, ARPE-19, grown on transwells as an in
vitro model of outer blood-retinal barrier. Exposure to infected monocytes
resulted in disruption of tight junction protein, ZO-1, and decrease in
transepithelial electrical resistance of retinal pigment epithelium. Supernatants
alone separated from infected monocytes also decreased transepithelial electrical
resistance and disrupted tight junction protein. Further investigation revealed
that the supernatants could activate focal adhesion kinase (FAK) signaling in
retinal pigment epithelium and the disruption was attenuated by FAK inhibitor.
The disrupted barrier was partly restored by blocking CXCL8, a FAK activating
factor secreted by infected monocytes. In this study, we demonstrated that
monocytes infected with T. gondii can disrupt outer blood-retinal barrier, which
is mediated by paracrinely activated FAK signaling. FAK signaling can be a target
of therapeutic approach to prevent negative influence of infected monocytes on
outer blood-retinal barrier.
PMID- 28406973
TI - TRE5-A retrotransposition profiling reveals putative RNA polymerase III
transcription complex binding sites on the Dictyostelium extrachromosomal rDNA
element.
AB - The amoeba Dictyostelium discoideum has a haploid genome in which two thirds of
the DNA encodes proteins. Consequently, the space available for selfish mobile
elements to expand without excess damage to the host genome is limited. The non
long terminal repeat retrotransposon TRE5-A maintains an active population in the
D. discoideum genome and apparently adapted to this gene-dense environment by
targeting positions ~47 bp upstream of tRNA genes that are devoid of protein
coding regions. Because only ~24% of tRNA genes are associated with a TRE5-A
element in the reference genome, we evaluated whether TRE5-A retrotransposition
is limited to this subset of tRNA genes. We determined that a tagged TRE5-A
element (TRE5-Absr) integrated at 384 of 405 tRNA genes, suggesting that
expansion of the current natural TRE5-A population is not limited by the
availability of targets. We further observed that TRE5-Absr targets the ribosomal
5S gene on the multicopy extrachromosomal DNA element that carries the ribosomal
RNA genes, indicating that TRE5-A integration may extend to the entire RNA
polymerase III (Pol III) transcriptome. We determined that both natural TRE5-A
and cloned TRE5-Absr retrotranspose to locations on the extrachromosomal rDNA
element that contain tRNA gene-typical A/B box promoter motifs without displaying
any other tRNA gene context. Based on previous data suggesting that TRE5-A
targets tRNA genes by locating Pol III transcription complexes, we propose that
A/B box loci reflect Pol III transcription complex assembly sites that possess a
function in the biology of the extrachromosomal rDNA element.
PMID- 28406974
TI - Resveratrol reduces the apoptosis induced by cigarette smoke extract by
upregulating MFN2.
AB - PURPOSE: The aim of this study was to investigate the effect of resveratrol (RSV)
on cigarette smoke extract (CSE)-induced cell apoptosis and mitochondrial
dysfunction in vitro, as well as changes in the MFN2 expression level. METHODS:
Cultured human bronchial epithelial (HBE) cells were initially treated with CSE
to induce apoptosis, followed by incubation either with or without RSV. Numerous
techniques were used to evaluate the outcomes of the present study, including a
cell counting kit-8 assay, real-time quantitative polymerase chain reaction (real
time qPCR), western blotting, JC-1 fluorescence, Hoechst 33342 staining, Annexin
V-PI flow cytometry apoptosis analyses, and siRNA technology. RESULTS: A 24 h
incubation in 3.5% CSE induced apoptosis in HBE cells, and pretreatment of HBE
cells with RSV (20 MUM) significantly suppressed the CSE-induced apoptosis,
prevented the CSE-induced decrease in MFN2 levels, suppressed BAX translocation
to the mitochondria, and prevented mitochondrial membrane potential loss and
cytochrome C release. However, following the transfection of MFN2 siRNA, the anti
apoptotic effects of RSV were significantly attenuated. CONCLUSION: The results
of the present study demonstrated that RSV may protect bronchial epithelial cells
from CS-induced apoptosis in vitro by preventing mitochondrial dysfunction, and
MFN2 may be associated with the anti-apoptotic functions of RSV in HBE cells.
PMID- 28406975
TI - Positional therapy in sleep apnoea - one fits all? What determines success in
positional therapy in sleep apnoea syndrome.
AB - INTRODUCTION: Positional therapy is a simple means of therapy in sleep apnoea
syndrome, but due to controversial or lacking evidence, it is not widely accepted
as appropriate treatment. In this study, we analysed data to positional therapy
with regard to successful reduction of AHI and predictors of success. METHODS:
All consecutive patients undergoing polysomnography between 2007 and 2011 were
analysed. We used a strict definition of positional sleep apnoea syndrome (supine
exclusive sleep apnoea syndrome) and of therapy used. Patients underwent
polysomnography initially and during follow-up. RESULTS: 1275 patients were
evaluated, 112 of which had supine-exclusive sleep apnoea syndrome (AHI 5-66/h,
median 13/h), 105 received positional therapy. With this treatment alone 75%
(70/105) reached an AHI <5/h, in the follow-up 1 year later 37% (37/105) of these
still had AHI<5/h, 46% (43/105) yielded an AHI between 5 and 10/h. Nine patient
switched to APAP due to deterioration, 3 wanted to try APAP due to comfort
reasons. At the last follow-up, 32% patients (34/105) were still on positional
therapy with AHI <5/h. BMI was a predictor for successful reduction of AHI, but
success was independent of sex, the presence of obstructive versus central sleep
apnoea, severity of sleep apnoea syndrome or co-morbidities. CONCLUSION:
Positional therapy may be a promising therapy option for patients with positional
sleep apnoea. With appropriate adherence it yields a reasonable success rate in
the clinical routine.
PMID- 28406976
TI - Elucidating the structure of an infectious protein.
PMID- 28406977
TI - Separation increases passive stress-coping behaviors during forced swim and
alters hippocampal dendritic morphology in California mice.
AB - Individuals within monogamous species form bonds that may buffer against the
negative effects of stress on physiology and behavior. In some species,
involuntary termination of the mother-offspring bond results in increased
symptoms of negative affect in the mother, suggesting that the parent-offspring
bond may be equally as important as the pair bond. To our knowledge, the extent
to which affect in paternal rodents is altered by involuntary termination of the
father-offspring bond is currently unknown. Here, we investigated to what extent
separation and paternal experience alters passive stress-coping behaviors and
dendritic morphology in hippocampal subfields of California mice (Peromyscus
californicus). Irrespective of paternal experience, separated mice displayed
shorter latencies to the first bout of immobility, longer durations of
immobility, and more bouts of immobility than control (non-separated) mice. This
effect of separation was exacerbated by paternal experience in some measures of
behavioral despair-separation from offspring further decreased the latency to
immobility and increased bouts of immobility. In the dentate gyrus, separation
reduced dendritic spine density regardless of paternal experience. Increased
spine density was observed on CA1 basal, but not apical, dendrites following
paternal experience. Regardless of offspring presence, fatherhood was associated
with reduced apical dendritic spine density in area CA3 of the hippocampus.
Separation enhanced complexity of both basal and apical dendrites in CA1, while
fatherhood reduced dendritic complexity in this region. Our data suggest that
forced dissolution of the pair bond induces passive stress-coping behaviors and
contributes to region-specific alterations in hippocampal structure in California
mouse males.
PMID- 28406978
TI - Combined assessment of serum folate and hemoglobin as biomarkers of brain amyloid
beta accumulation.
AB - A relationship between Alzheimer's disease (AD) and folate has been reported.
Amyloid positron emission tomography (PET) is currently one of the most reliable
biomarkers for AD. We investigated the correlation between serum folate levels
and amyloid imaging to clarify whether serum folate could be a biomarker for AD.
We also examined the usefulness of a combined assessment of serum folate levels
and red blood cell hemoglobin content. Apolipoprotein E (APOE) gene polymorphisms
were also assessed. Serum folate levels and hemoglobin content were evaluated by
receiver operating characteristic analysis for their diagnostic capability as AD
biomarkers relating to brain amyloid beta accumulation. The area under the ROC
curve (AUC) for serum folate was 0.136 (95% confidence interval [CI]: 0.000
0.312; p = 0.016). The AUC for hemoglobin content was 0.848 (95% CI: 0.661-1.000;
p = 0.021). Therefore, the folate deficiency with low folate levels or the non
anaemia with high hemoglobin content levels were found to have a high probability
of also testing positive for amyloid. Furthermore, eight patients were found to
be folate deficiency and non-anaemia, those who were consist of 7 amyloid
positive patients (87.5%), and only one of the amyloid negative patients (12.5%).
These results suggest that a deficiency of serum folate and high hemoglobin
levels may reflect an increased risk of amyloid beta accumulation in the brain.
Additionally, we demonstrated that these biomarkers could enhance the
effectiveness of APOE as an AD biomarker. This study reveals that the combined
assessment of serum folate levels and red blood cell hemoglobin content may be a
useful biomarker for amyloid beta accumulation in the brain. We also found that
the combination of serum folate levels and hemoglobin content is a more specific
and sensitive blood biomarker for AD than APOE or folate alone. These findings
may be used to support clinical diagnosis of AD using a simple blood test.
PMID- 28406979
TI - Correction: Gut dysbiosis is associated with metabolism and systemic inflammation
in patients with ischemic stroke.
AB - [This corrects the article DOI: 10.1371/journal.pone.0171521.].
PMID- 28406980
TI - Correction: Tensor based multichannel reconstruction for breast tumours
identification from DCE-MRIs.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172111.].
PMID- 28406981
TI - Human exploitation assisting a threatened species? The case of muttonbirders and
Buller's albatross.
AB - Albatrosses are flexible and adaptable predators, relying on live prey as well as
carrion. Use of predictable food sources and reliance on human-produced resources
are well-known trait in long-range feeders like albatrosses and petrels. Breeding
Buller's albatrosses studied at Solander I. (Hautere), New Zealand fed their
chicks the remains of sooty shearwater juveniles (titi in Maori), which are
harvested from nearby muttonbirding sites. Evidence of this food type was found
at over 10% of nests examined, and 17-40% birds that were fitted with GPS loggers
visited muttonbirding sites in this and previous studies. Muttonbirding is a
traditional practice that has continued for centuries, with up to 120 tonnes of
offal discharged to the sea annually during the present day harvest. It coincides
with the energetically-demanding early chick period for the albatrosses. Our
finding suggests that the offal may be an important, but overlooked element in
the albatross diet. As an important supplementary food for the albatrosses it is
likely to have contributed to the 3% per annum growth of their populations since
the first comprehensive population surveys in 1969.
PMID- 28406983
TI - An algorithm for constructing the skeleton graph of degenerate systems of linear
inequalities.
AB - Derive the quantitative predictions of constraint-based models require of
conversion algorithms to enumerate and construct the skeleton graph conformed by
the extreme points of the feasible region, where all constraints in the model are
fulfilled. The conversion is problematic when the system of linear constraints is
degenerate. This paper describes a conversion algorithm that combines the best of
two methods: the incremental slicing of cones that defeats degeneracy and
pivoting for a swift traversal of the set of extreme points. An extensive
computational practice uncovers two complementary classes of conversion problems.
The two classes are distinguished by a practical measure of complexity that
involves the input and output sizes. Detailed characterizations of the complexity
classes and the corresponding performances of the algorithm are presented. For
the benefit of implementors, a simple example illustrates the stages of the
exposition.
PMID- 28406982
TI - Novel decay dynamics revealed for virus-mediated drug activation in
cytomegalovirus infection.
AB - Human cytomegalovirus (CMV) infection is a substantial cause of morbidity and
mortality in immunocompromised hosts and globally is one of the most important
congenital infections. The nucleoside analogue ganciclovir (GCV), which requires
initial phosphorylation by the viral UL97 kinase, is the mainstay for treatment.
To date, CMV decay kinetics during GCV therapy have not been extensively
investigated and its clinical implications not fully appreciated. We measured CMV
DNA levels in the blood of 92 solid organ transplant recipients with CMV disease
over the initial 21 days of ganciclovir therapy and identified four distinct
decay patterns, including a new pattern exhibiting a transient viral rebound
(Hump) following initial decline. Since current viral dynamics models were unable
to account for this Hump profile, we developed a novel multi-level model, which
includes the intracellular role of UL97 in the continued activation of
ganciclovir, that successfully described all the decline patterns observed.
Fitting the data allowed us to estimate ganciclovir effectiveness in vivo (mean
92%), infected cell half-life (mean 0.7 days), and other viral dynamics
parameters that determine which of the four kinetic patterns will ensue. An
important clinical implication of our results is that the virological efficacy of
GCV operates over a broad dose range. The model also raises the possibility that
GCV can drive replication to a new lower steady state but ultimately cannot fully
eradicate it. This model is likely to be generalizable to other anti-CMV
nucleoside analogs that require activation by viral enzymes such as UL97 or its
homologues.
PMID- 28406984
TI - Social influence on selection behaviour: Distinguishing local- and global-driven
preferential attachment.
AB - Social influence drives human selection behaviours when numerous objects
competing for limited attentions, which leads to the 'rich get richer' dynamics
where popular objects tend to get more attentions. However, evidences have been
found that, both the global information of the whole system and the local
information among one's friends have significant influence over the one's
selection. Consequently, a key question raises that, it is the local information
or the global information more determinative for one's selection? Here we compare
the local-based influence and global-based influence. We show that, the selection
behaviour is mainly driven by the local popularity of the objects while the
global popularity plays a supplementary role driving the behaviour only when
there is little local information for the user to refer to. Thereby, we propose a
network model to describe the mechanism of user-object interaction evolution with
social influence, where the users perform either local-driven or global-driven
preferential attachments to the objects, i.e., the probability of an objects to
be selected by a target user is proportional to either its local popularity or
global popularity. The simulation suggests that, about 75% of the attachments
should be driven by the local popularity to reproduce the empirical observations.
It means that, at least in the studied context where users chose businesses on
Yelp, there is a probability of 75% for a user to make a selection according to
the local popularity. The proposed model and the numerical findings may shed some
light on the study of social influence and evolving social systems.
PMID- 28406986
TI - Correction: The Area of Secondary Hyperalgesia following Heat Stimulation in
Healthy Male Volunteers: Inter- and Intra-Individual Variance and
Reproducibility.
AB - [This corrects the article DOI: 10.1371/journal.pone.0155284.].
PMID- 28406985
TI - Metformin inhibited esophageal squamous cell carcinoma proliferation in vitro and
in vivo and enhanced the anti-cancer effect of cisplatin.
AB - Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor
prognosis in China. Chemotherapy now is one of the most frequently used
treatments for patients with ESCC in middle or late stage, however the effects
were often limited by increased chemoresistance or treatment toxicity. So it is
urgent to find new drugs to treat ESCC patients. Metformin with low cost and
toxicity has proved to have anti-cancer effects in a numerous cancers, while its
role and mechanism in ESCC has seldom been studied. In the present study, we
found that metformin exhibited not only an anti-proliferation ability in a dose
and time dependent manner but also a proapoptosis effect in a dose dependent
manner in ESCC cell line KYSE450. Our in vivo experiment also showed that
metformin markedly inhibited KYSE450 xenograft tumors growth compared to those
treated with normal saline. What's more, no obvious toxic reactions were
observed. To further explore the underlying mechanism, we found that metformin
treatment could significantly damp the expression of 4EBP1 and S6K1 in KYSE 450
cells in vitro and in vivo, furthermore, the p-4EBP1 and p-S6K1 expression in
KYSE 450 cells were also inhibited greatly in vitro and in vivo. During the
therapy of cancer, in order to overcome side effects, combination therapy was
often used. In this paper, we demonstrated that metformin potentiated the effects
of cisplatin via inhibiting cell proliferation and promoting cell apoptosis.
Taken together, metformin owned the potential anti-cancer effect on ESCC in
monotherapy or was combined with cisplatin and these results laid solid basis for
the use of metformin in ESCC.
PMID- 28406987
TI - Arabidopsis leucine-rich repeat receptor-like kinase NILR1 is required for
induction of innate immunity to parasitic nematodes.
AB - Plant-parasitic nematodes are destructive pests causing losses of billions of
dollars annually. An effective plant defence against pathogens relies on the
recognition of pathogen-associated molecular patterns (PAMPs) by surface
localised receptors leading to the activation of PAMP-triggered immunity (PTI).
Extensive studies have been conducted to characterise the role of PTI in various
models of plant-pathogen interactions. However, far less is known about the role
of PTI in roots in general and in plant-nematode interactions in particular. Here
we show that nematode-derived proteinaceous elicitor/s is/are capable of inducing
PTI in Arabidopsis in a manner dependent on the common immune co-receptor BAK1.
Consistent with the role played by BAK1, we identified a leucine-rich repeat
receptor-like kinase, termed NILR1 that is specifically regulated upon infection
by nematodes. We show that NILR1 is essential for PTI responses initiated by
nematodes and nilr1 loss-of-function mutants are hypersusceptible to a broad
category of nematodes. To our knowledge, NILR1 is the first example of an immune
receptor that is involved in induction of basal immunity (PTI) in plants or in
animals in response to nematodes. Manipulation of NILR1 will provide new options
for nematode control in crop plants in future.
PMID- 28406988
TI - Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2
positive tumor imaging.
AB - A high level of HER2 expression in breast cancer correlates with a higher tumor
growth rate, high metastatic potential, and a poor long-term patient survival
rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2
overexpression by preventing HER2 dimerization. In this study, a combination
protocol of molecular dynamics modeling and MM/GBSA binding free energy
calculations was applied to design peptides that interact with HER2 based on the
HER2/pertuzumab crystal structure. Based on a beta hairpin in pertuzumab from
Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were
carried out in silico to improve the binding free energy of the hairpin that
interacts with the Phe256-Lys314 of the HER2 protein. Combined the use of one
bead-one-compound library screening, among all the mutations, a peptide (58F63Y)
with the lowest binding free energy was confirmed experimentally to have the
highest affinity, and it may be used as a new probe in diagnosing and treating
HER2-positive breast cancer.
PMID- 28406989
TI - ESCDL-1, a new cell line derived from chicken embryonic stem cells, supports
efficient replication of Mardiviruses.
AB - Marek's disease virus is the etiological agent of a major lymphoproliferative
disorder in poultry and the prototype of the Mardivirus genus. Primary avian
somatic cells are currently used for virus replication and vaccine production,
but they are largely refractory to any genetic modification compatible with the
preservation of intact viral susceptibility. We explored the concept of induction
of viral replication permissiveness in an established pluripotent chicken
embryonic stem cell-line (cES) in order to derive a new fully susceptible cell
line. Chicken ES cells were not permissive for Mardivirus infection, but as soon
as differentiation was triggered, replication of Marek's disease virus was
detected. From a panel of cyto-differentiating agents, hexamethylene bis
(acetamide) (HMBA) was found to be the most efficient regarding the induction of
permissiveness. These initial findings prompted us to analyse the effect of HMBA
on gene expression, to derive a new mesenchymal cell line, the so-called ESCDL-1,
and monitor its susceptibility for Mardivirus replication. All Mardiviruses
tested so far replicated equally well on primary embryonic skin cells and on
ESCDL-1, and the latter showed no variation related to its passage number in its
permissiveness for virus infection. Viral morphogenesis studies confirmed
efficient multiplication with, as in other in vitro models, no extra-cellular
virus production. We could show that ESCDL-1 can be transfected to express a
transgene and subsequently cloned without any loss in permissiveness.
Consequently, ESCDL-1 was genetically modified to complement viral gene deletions
thus yielding stable trans-complementing cell lines. We herein claim that
derivation of stable differentiated cell-lines from cES cell lines might be an
alternative solution to the cultivation of primary cells for virology studies.
PMID- 28406990
TI - Under threat by popular vote: German-speaking immigrants' affect and cognitions
following the Swiss vote against mass immigration.
AB - A popular initiative in support of regulating future immigration to Switzerland
was accepted by the electorate in 2014. Assuming that the initiative acted as an
exclusionary threat for current immigrants of Switzerland, we conducted an online
survey among a sample of highly-skilled German-speaking immigrants ("expats").
Participants reported having experienced negative affect following the vote.
Moreover, having a more left-wing orientation, living in a political constituency
that had voted pro-regulation and having proportionally few Swiss friends
positively predicted negative affect following the vote. Negative affect was
associated with a reported negative change in one's attitudes towards
Switzerland, increased considerations to leave the country, and impaired
satisfaction with life. In sum, the results suggest that a powerful exclusionary
threat such as a national vote may be experienced as distressful by highly
skilled immigrants currently living in the country.
PMID- 28406991
TI - A mathematical model for active contraction in healthy and failing myocytes and
left ventricles.
AB - Cardiovascular disease is one of the leading causes of death worldwide, in
particular myocardial dysfunction, which may lead to heart failure eventually.
Understanding the electro-mechanics of the heart will help in developing more
effective clinical treatments. In this paper, we present a multi-scale electro
mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law
was used to describe the passive myocardial response in tissue level, a modified
Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual
myocytes, and the active tension was described using the Niederer-Hunter-Smith
myofilament model. We first studied the electro-mechanics coupling in a single
myocyte in the healthy and diseased left ventricle, and then the single cell
model was embedded in a dynamic LV model to investigate the compensation
mechanism of LV pump function due to myocardial dysfunction caused by abnormality
in cellular calcium dynamics. The multi-scale LV model was solved using an in
house developed hybrid immersed boundary method with finite element extension.
The predictions of the healthy LV model agreed well with the clinical
measurements and other studies, and likewise, the results in the failing states
were also consistent with clinical observations. In particular, we found that a
low level of intracellular Ca2+ transient in myocytes can result in LV pump
function failure even with increased myocardial contractility, decreased systolic
blood pressure, and increased diastolic filling pressure, even though they will
increase LV stroke volume. Our work suggested that treatments targeted at
increased contractility and lowering the systolic blood pressure alone are not
sufficient in preventing LV pump dysfunction, restoring a balanced physiological
Ca2+ handling mechanism is necessary.
PMID- 28406992
TI - Expanded antiretroviral treatment, sexual networks, and condom use: Treatment as
prevention unlikely to succeed without partner reduction among men who have sex
with men in China.
AB - BACKGROUND: To project the impact of partner reduction on preventing new HIV
infections among men who have sex with men (MSM) under varying conditions of
enhanced HIV testing and treatment (T&T) and condom use in Beijing, China.
METHODS AND FINDINGS: A complex network model was fitted to predict the number of
new HIV infections averted from 2014 to 2023 under four scenarios of sexual
behavior risk reduction (S)-S1: Male sexual partners decrease (reduced by a
random value m from 1-50) while condom use increases (risk constant p is a random
value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1,
50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or
decreases (p 0.2, 1.8); S4: Only MSM with >=100 male sexual partners reduce their
partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will
reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three
most influential factors are: T&T coverage; partner reduction (m); and the
background risk (p). Under scenarios 1-4 of sexual behavioral changes with
enhanced T&T interventions, the cumulative HIV new infections prevented over the
10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for
S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR
4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if
there were a substantial reduction of male sexual partners and/or expanded condom
use. CONCLUSION: Partner reduction is a vital factor within HIV combination
interventions to reduce HIV incidence among Beijing MSM, with substantial
additional benefits derived from condom use. T&T without substantial partner
reduction and increased condom use is less promising unless its implementation
were extremely (and improbably) efficient.
PMID- 28406993
TI - Topical and systemic immunoreaction triggered by intravesical chemotherapy in an
N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model.
AB - Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy
to prevent progression and recurrence of non-muscle invasive bladder cancer
(NMIBC). Although the immunoreaction elicited by BCG treatment is well
documented, those induced by intravesical treatment with chemotherapeutic agents
are much less known. We investigated the immunological profiles caused by
mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4
hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model.
Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly
divided into six groups and treated with chemotherapeutic agents once a week for
four weeks. After last treatment, bladder and serum samples were analyzed for
cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1)
using immunohistochemistry staining. Serum and urine cytokine levels were
evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties
similar to those of BCG. These included changes in immune cells that resulted in
fewer M2 macrophages and regulatory T cells around tumors. This result was
compatible with those in human samples. Intravesical chemotherapy also induced
systemic changes in cytokines, especially urinary interleukin (IL)-17A and
granulocyte colony stimulating factor (G-CSF), as well as in the distribution of
blood neutrophils, lymphocytes, and monocytes. Our findings suggest that
intravesical treatment with mitomycin C and adriamycin suppresses protumoral
immunity while enhancing anti-tumor immunity, possibly through the action of
specific cytokines. A better understanding of the immunoreaction induced by
chemotherapeutic agents can lead to improved outcomes and fewer side effects in
intravesical chemotherapy against NMIBC.
PMID- 28406994
TI - Neisseria gonorrhoeae infects the human endocervix by activating non-muscle
myosin II-mediated epithelial exfoliation.
AB - Colonization and disruption of the epithelium is a major infection mechanism of
mucosal pathogens. The epithelium counteracts infection by exfoliating damaged
cells while maintaining the mucosal barrier function. The sexually transmitted
bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract
primarily from the endocervix, causing gonorrhea. However, the mechanism by which
GC overcome the mucosal barrier remains elusive. Using a new human tissue model,
we demonstrate that GC can penetrate into the human endocervix by inducing the
exfoliation of columnar epithelial cells. We found that GC colonization causes
endocervical epithelial cells to shed. The shedding results from the disassembly
of the apical junctions that seal the epithelial barrier. Apical junction
disruption and epithelial exfoliation increase GC penetration into the
endocervical epithelium without reducing bacterial adherence to and invasion into
epithelial cells. Both epithelial exfoliation and junction disruption require the
activation and accumulation of non-muscle myosin II (NMII) at the apical surface
and GC adherent sites. GC inoculation activates NMII by elevating the levels of
the cytoplasmic Ca2+ and NMII regulatory light chain phosphorylation. Piliation
of GC promotes, but the expression of a GC opacity-associated protein variant,
OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII
activation and reorganization and Ca2+ flux. The inhibitory effects of OpaH lead
to reductions in junction disruption, epithelial exfoliation, and GC penetration.
Therefore, GC phase variation can modulate infection in the human endocervix by
manipulating the activity of NMII and epithelial exfoliation.
PMID- 28406995
TI - Cell-based evaluation of changes in coagulation activity induced by
antineoplastic drugs for the treatment of acute myeloid leukemia.
AB - Idarubicin (IDR), cytarabine (AraC), and tamibarotene (Am80) are effective for
treatment of acute myeloid leukemia (AML). In acute leukemia, the incidence of
venous thromboembolism or disseminated intravascular coagulation is associated
with induction chemotherapy. Procoagulant effects of IDR, AraC, and Am80 were
investigated in a vascular endothelial cell line EAhy926 and AML cell lines HL60
(AML M2), NB4 (AML M3, APL), and U937 (AML M5), focusing on tissue factor (TF),
phosphatidylserine (PS), and thrombomodulin (TM). IDR induced procoagulant
activity on the surface of vascular endothelial and AML cell lines. Expression of
TF antigen, TM antigen, and PS were induced by IDR on the surface of each cell
line, whereas expression of TF and TM mRNAs were unchanged. Conversely, Am80
decreased TF exposure and procoagulant activity, and increased TM exposure on NB4
cells. In NB4 cells, we observed downregulation of TF mRNA and upregulation of TM
mRNA. These data suggest IDR may induce procoagulant activity in vessels by
apoptosis through PS exposure and/or TF expression on vascular endothelial and
AML cell lines. Am80 may suppress blood coagulation through downregulation of TF
expression and induction of TM expression. Our methods could be useful to
investigate changes in procoagulant activity induced by antineoplastic drugs.
PMID- 28406996
TI - Ultrasensitivity and fluctuations in the Barkai-Leibler model of chemotaxis
receptors in Escherichia coli.
AB - A stochastic version of the Barkai-Leibler model of chemotaxis receptors in
Escherichia coli is studied here with the goal of elucidating the effects of
intrinsic network noise in their conformational dynamics. The model was
originally proposed to explain the robust and near-perfect adaptation of E. coli
observed across a wide range of spatially uniform attractant/repellent (ligand)
concentrations. In the model, a receptor is either active or inactive and can
stochastically switch between the two states. The enzyme CheR methylates inactive
receptors while CheB demethylates active receptors and the probability for a
receptor to be active depends on its level of methylation and ligand occupation.
In a simple version of the model with two methylation sites per receptor (M = 2),
we show rigorously, under a quasi-steady state approximation, that the mean
active fraction of receptors is an ultrasensitive function of [CheR]/[CheB] in
the limit of saturating receptor concentration. Hence the model shows zero-order
ultrasensitivity (ZOU), similar to the classical two-state model of covalent
modification studied by Goldbeter and Koshland (GK). We also find that in the
limits of extremely small and extremely large ligand concentrations, the system
reduces to two different two-state GK modules. A quantitative measure of the
spontaneous fluctuations in activity is provided by the variance [Formula: see
text] in the active fraction, which is estimated mathematically under linear
noise approximation (LNA). It is found that [Formula: see text] peaks near the
ZOU transition. The variance is a non-monotonic, but weak function of ligand
concentration and a decreasing function of receptor concentration. Gillespie
simulations are also performed in models with M = 2, 3 and 4. For M = 2,
simulations show excellent agreement with analytical results obtained under LNA.
Numerical results for M = 3 and M = 4 are qualitatively similar to our
mathematical results in M = 2; while all the models show ZOU in mean activity,
the variance is found to be smaller for larger M. The magnitude of receptor noise
deduced from available experimental data is consistent with our predictions. A
simple analysis of the downstream signaling pathway shows that this noise is
large enough to affect the motility of the organism, and may have a beneficial
effect on it. The response of mean receptor activity to small time-dependent
changes in the external ligand concentration is computed within linear response
theory, and found to have a bilobe form, in agreement with earlier experimental
observations.
PMID- 28406997
TI - Large inter-individual and intra-individual variability in the effect of
perceptual load.
AB - This study examined whether the recurrent difficulty to replicate results
obtained with paradigms measuring distractor processing as a function of
perceptual load is due to individual differences. We first reanalyzed, at the
individual level, the data of eight previously reported experiments. These
reanalyses revealed substantial inter-individual differences, with particularly
low percentage of participants whose performance matched the load theory's
predictions (i.e., larger distractor interference with low than high levels of
load). Moreover, frequently the results were opposite to the theory's predictions
larger interference in the high than low load condition; and often a reversed
compatibility effect emerged-better performance in the incompatible than neutral
condition. Subsequently, seven observers participated in five identical
experimental sessions. If the observed inter-individual differences are due to
some stable trait or perceptual capacity, similar results should have emerged in
all sessions of a given participant. However, all seven participants showed large
between-sessions variations with similar patterns to those found between
participants. These findings question the theoretical foundation implemented with
these paradigms, as none of the theories suggested thus far can account for such
inter- and intra-individual differences. Thus, these paradigms should be used
with caution until further research will provide better understanding of what
they actually measure.
PMID- 28406999
TI - Dorsal root ganglia neurite outgrowth measured as a function of changes in
microelectrode array resistance.
AB - Current research in prosthetic device design aims to mimic natural movements
using a feedback system that connects to the patient's own nerves to control the
device. The first step in using neurons to control motion is to make and maintain
contact between neurons and the feedback sensors. Therefore, the goal of this
project was to determine if changes in electrode resistance could be detected
when a neuron extended a neurite to contact a sensor. Dorsal root ganglia (DRG)
were harvested from chick embryos and cultured on a collagen-coated carbon
nanotube microelectrode array for two days. The DRG were seeded along one side of
the array so the processes extended across the array, contacting about half of
the electrodes. Electrode resistance was measured both prior to culture and after
the two day culture period. Phase contrast images of the microelectrode array
were taken after two days to visually determine which electrodes were in contact
with one or more DRG neurite or tissue. Electrodes in contact with DRG neurites
had an average change in resistance of 0.15 MOmega compared with the electrodes
without DRG neurites. Using this method, we determined that resistance values can
be used as a criterion for identifying electrodes in contact with a DRG neurite.
These data are the foundation for future development of an autonomous feedback
resistance measurement system to continuously monitor DRG neurite outgrowth at
specific spatial locations.
PMID- 28406998
TI - Structure and dynamics of the gut bacterial microbiota of the bark beetle,
Dendroctonus rhizophagus (Curculionidae: Scolytinae) across their life stages.
AB - Bark beetles play an important role as agents of natural renovation and
regeneration in coniferous forests. Several studies have documented the metabolic
capacity of bacteria associated with the gut, body surface, and oral secretions
of these insects; however, little is known about how the bacterial community
structure changes during the life cycle of the beetles. This study represents the
first comprehensive analysis of the bacterial community of the gut of the bark
beetle D. rhizophagus during the insect's life cycle using 454 pyrosequencing. A
total of 4 bacterial phyla, 7 classes, 15 families and 23 genera were identified.
The alpha-diversity was low, as demonstrated in previous studies. The dominant
bacterial taxa belonged to the Enterobacteriaceae and Pseudomonadaceae families.
This low alpha-diversity can be attributed to the presence of defensive chemical
compounds in conifers or due to different morpho-physiological factors in the gut
of these insects acting as strong selective factors. Members of the genera
Rahnella, Serratia, Pseudomonas and Propionibacterium were found at all life
stages, and the first three genera, particularly Rahnella, were predominant
suggesting the presence of a core microbiome in the gut. Significant differences
in beta-diversity were observed, mainly due to bacterial taxa present at low
frequencies and only in certain life stages. The predictive functional profiling
indicated metabolic pathways related to metabolism of amino acids and
carbohydrates, and membrane transport as the most significant in the community.
These differences in the community structure might be due to several selective
factors, such as gut compartmentalization, physicochemical conditions, and
microbial interactions.
PMID- 28407000
TI - Blindness enhances auditory obstacle circumvention: Assessing echolocation,
sensory substitution, and visual-based navigation.
AB - Performance for an obstacle circumvention task was assessed under conditions of
visual, auditory only (using echolocation) and tactile (using a sensory
substitution device, SSD) guidance. A Vicon motion capture system was used to
measure human movement kinematics objectively. Ten normally sighted participants,
8 blind non-echolocators, and 1 blind expert echolocator navigated around a 0.6 x
2 m obstacle that was varied in position across trials, at the midline of the
participant or 25 cm to the right or left. Although visual guidance was the most
effective, participants successfully circumvented the obstacle in the majority of
trials under auditory or SSD guidance. Using audition, blind non-echolocators
navigated more effectively than blindfolded sighted individuals with fewer
collisions, lower movement times, fewer velocity corrections and greater obstacle
detection ranges. The blind expert echolocator displayed performance similar to
or better than that for the other groups using audition, but was comparable to
that for the other groups using the SSD. The generally better performance of
blind than of sighted participants is consistent with the perceptual enhancement
hypothesis that individuals with severe visual deficits develop improved auditory
abilities to compensate for visual loss, here shown by faster, more fluid, and
more accurate navigation around obstacles using sound.
PMID- 28407001
TI - Effect of hypoxia on the retina and superior colliculus of neonatal pigs.
AB - PURPOSE: To evaluate the effect of hypoxia on the neonatal pig retina and brain,
we analysed the retinal ganglion cells (RGCs) and neurons in the superior
colliculus, as well as the response of astrocytes in both these central nervous
system (CNS) structures. METHODS: Newborn pigs were exposed to 120 minutes of
hypoxia, induced by decreasing the inspiratory oxygen fraction (FiO2: 10-15%),
followed by a reoxygenation period of 240 minutes (FiO2: 21-35%). RGCs were
quantified using Brn3a, a specific nuclear marker for these cells, and apoptosis
was assessed through the appearance of active caspase-3. A morphometric analysis
of the cytoskeleton of astrocytes (identified with GFAP) was performed in both
the retina and superior colliculus. RESULTS: Hypoxia produced no significant
change in the RGCs, although, it did induce a 37.63% increase in the number of
active caspase-3 positive cells in the superior colliculus. This increase was
particularly evident in the superficial layers of the superior colliculus, where
56.93% of the cells were positive for active caspase-3. In addition, hypoxia
induced changes in the morphology of the astrocytes in the superior colliculus
but not in the retina. CONCLUSIONS: Hypoxia in the neonatal pig does not affect
the retina but it does affect more central structures in the brain, increasing
the number of apoptotic cells in the superior colliculus and inducing changes in
astrocyte morphology. This distinct sensibility to hypoxia may pave the way to
design specific approaches to combat the effects of hypoxia in specific areas of
the CNS.
PMID- 28407002
TI - Attrition and performance of community college transfers.
AB - Community colleges are an important part of the US higher education landscape,
yet the aptitude and preparedness of student transfers to baccalaureate
institutions is often called into question. Examining transcript records and
demographic information of nearly 70,000 students across over 15 years of
registrar records at a public university, this study performed a descriptive
analysis of the persistence, performance, and academic migration patterns of
community college transfers, transfers from four-year institutions, and freshmen
entrants. We found little difference between community college transfers and
freshmen entrants in terms of post-transfer grades and persistence. Transfers
from four-year institutions had higher grades but also had higher attrition rates
than their peers. This study also found no strong evidence of transfer shock on
students' post-transfer grades. When examining the tendencies of students to
shift fields of study during their educational pursuits, the academic migration
patterns of transfer students were more concentrated than those of freshmen
entrants.
PMID- 28407003
TI - Assessment of the implementation of community-led total sanitation, hygiene, and
associated factors in Diretiyara district, Eastern Ethiopia.
AB - Based on the sustainable development goals, the United Nations plans to achieve
equitable sanitation and hygiene for all and to end open defecation by 2030. In
Ethiopia, 60% to 80% of health problems are due to communicable diseases
attributable to unsafe water supply, unhygienic and unsanitary waste management,
which are directly linked to the practice of open defecation. This study has
aimed at assessing the implementation of community-led total sanitation and
hygiene (CLTSH) and associated factors. A community-based cross-sectional study
design involving 420 of the 7,225 households found in Diretiyara district was
conducted in June 2014. Both quantitative and qualitative data were collected.
Using Logistic Regressions, bivariate and multivariate analyses were computed.
This study showed that 66% of the respondents have knowledge of CLTSH. Eighty
nine percent of the respondents have latrine, of which 78% were constructed after
the introduction of CLTSH. Eleven percent of the respondents reported to have
defected in the open field and 15% of them reported that they had been recently
exposed to diarrhea diseases. The occurrence of diarrheal disease was
significantly associated with the extent of latrine ownership [AOR = 2.48; 95% CI
1.00, 6.12]. Attitude and perception parameters were significantly associated
with consistent latrine utilization. Respondents who agreed that "Open defecation
is preferred due to the unpleasant smell and heat from the Latrine'' [COR = 0.58;
95% CI 0.34, 0.99] were 58% less likely to use the latrine consistently. In
conclusion, CLTSH has increased the extent of latrine ownership and decreased
practice of open defecation, and yet, intermittent latrine use and poor hygienic
practice were reported. Although some fundamental misconceptions were reported,
the majority of the respondents have accepted CLTSH approach as a means to ending
open defecation in their village. Health extension workers and local authorities
should give emphasis to achieving sustainable behavioral change on improved
sanitation and good hygiene practices.
PMID- 28407004
TI - Epigenetically repressing human cytomegalovirus lytic infection and reactivation
from latency in THP-1 model by targeting H3K9 and H3K27 histone demethylases.
AB - Human Cytomegalovirus (hCMV) infects a broad range of the population and
establishes life-long latency in the infected individuals. Periodically the
latently infected virus can reactivate and becomes a significant cause of
morbidity and mortality in immunocompromised individuals. In latent infection,
the viral genome is suppressed in a heterochromatic state and viral gene
transcription is silenced. Upon reactivation, the repressive chromatin is
remodeled to an active form, allowing viral lytic gene transcription, initiated
by the expression of viral Immediate Early (IE) genes. During this process, a
number of histone modification enzymes, including histone demethylases (HDMs),
play important roles in driving IE expression, but the mechanisms involved are
not fully understood. To get a better understanding of these mechanisms, we
focused on two HDMs, KDM4 and KDM6, which reverse the repressive histone H3
lysine 9 and lysine 27 methylation, respectively. Our studies show that in lytic
infection, both demethylases are important in the activation of viral IE gene
expression. Simultaneous disruption of both via genetic or chemical methods leads
to severely impaired viral IE gene expression and viral replication.
Additionally, in an experimental latency-reactivation model in THP-1 cells, the
KDM6 family member JMJD3 is induced upon viral reactivation and its knockdown
resulted in reduced IE gene transcription. These findings suggest pharmacological
inhibition of these HDMs may potentially block hCMV lytic infection and
reactivation, and control the viral infection associated diseases, which are of
significant unmet medical needs.
PMID- 28407005
TI - C1q ablation exacerbates amyloid deposition: A study in a transgenic mouse model
of ATTRV30M amyloid neuropathy.
AB - ATTRV30M amyloid neuropathy is a lethal autosomal dominant sensorimotor and
autonomic neuropathy, caused by deposition of amyloid fibrils composed of
aberrant transthyretin (TTR). Ages of onset and penetrance exhibit great
variability and genetic factors have been implicated. Complement activation co
localizes with amyloid deposits in amyloidotic neuropathy and is possibly
involved in the kinetics of amyloidogenesis. A candidate gene approach has
recently identified C1q polymorphisms to correlate with disease onset in a
Cypriot cohort of patients with ATTRV30M amyloid neuropathy. In the current study
we use a double transgenic mouse model of ATTRV30M amyloid neuropathy in which
C1q is ablated to elucidate further a possible modifier role for C1q. Amyloid
deposition is found to be increased by 60% in the absence of C1q. Significant up
regulation is also recorded in apoptotic and cellular stress markers reflecting
extracellular toxicity of pre-fibrillar and fibrillar TTR. Our data further
indicate that in the absence of C1q there is marked reduction of macrophages in
association with amyloid deposits and thus less effective phagocytosis of TTR.
PMID- 28407006
TI - Functional and structural characterization of plastidic starch phosphorylase
during barley endosperm development.
AB - The production of starch is essential for human nutrition and represents a major
metabolic flux in the biosphere. The biosynthesis of starch in storage organs
like barley endosperm operates via two main pathways using different substrates:
starch synthases use ADP-glucose to produce amylose and amylopectin, the two
major components of starch, whereas starch phosphorylase (Pho1) uses glucose-1
phosphate (G1P), a precursor for ADP-glucose production, to produce alpha-1,4
glucans. The significance of the Pho1 pathway in starch biosynthesis has remained
unclear. To elucidate the importance of barley Pho1 (HvPho1) for starch
biosynthesis in barley endosperm, we analyzed HvPho1 protein production and
enzyme activity levels throughout barley endosperm development and characterized
structure-function relationships of HvPho1. The molecular mechanisms underlying
the initiation of starch granule biosynthesis, that is, the enzymes and
substrates involved in the initial transition from simple sugars to
polysaccharides, remain unclear. We found that HvPho1 is present as an active
protein at the onset of barley endosperm development. Notably, purified
recombinant protein can catalyze the de novo production of alpha-1,4-glucans
using HvPho1 from G1P as the sole substrate. The structural properties of HvPho1
provide insights into the low affinity of HvPho1 for large polysaccharides like
starch or amylopectin. Our results suggest that HvPho1 may play a role during the
initiation of starch biosynthesis in barley.
PMID- 28407007
TI - Polaprezinc combined with clarithromycin-based triple therapy for Helicobacter
pylori-associated gastritis: A prospective, multicenter, randomized clinical
trial.
AB - The efficacy and safety of polaprezinc combined with triple therapy was compared
with triple therapy alone in the eradication of Helicobacter pylori. A
randomized, parallel-group, open-label, controlled, prospective multicenter study
was conducted in 11 cities in China. Treatment-naive patients with H. pylori
associated gastritis were randomly assigned to one of three arms for a 14-day
treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and
clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm
B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy
alone. The rate of H. pylori eradication was the primary endpoint. Secondary
endpoints were symptom improvement and lower incidence of adverse events. 303
patients completed the study- 106, 96, and 101 patients in Arms A, B, and C,
respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori
eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to
Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P
= 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication
was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C
(61.4%) (P < 0.01), whereas there was no significant difference between Arms A
and B (P = 0.62). All three groups reported significant symptom improvement at 7,
14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse
event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C
(1.9%) (P = 0.02). There were no serious adverse events in any group. It appears
that standard dose polaprezinc combined with triple therapy can significantly
improve the H. pylori eradication rate, without an increase in toxicity.
PMID- 28407008
TI - Dysregulated signaling, proliferation and apoptosis impact on the pathogenesis of
TCRgammadelta+ T cell large granular lymphocyte leukemia.
AB - TCRgammadelta+ T-LGL leukemia is a rare form of chronic mature T cell disorders
in elderly, which is generally characterized by a persistently enlarged
CD3+CD57+TCRgammadelta+ large granular lymphocyte population in the peripheral
blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most
patients being largely asymptomatic, although neutropenia, fatigue and B symptoms
and underlying diseases such as autoimmune diseases or malignancies are also
often observed. The etiology of TCRgammadelta+ T-LGL proliferations is largely
unknown. Here, we aimed to investigate underlying molecular mechanisms of these
rare proliferations by performing gene expression profiling of TCRgammadelta+ T
LGL versus normal TCRgammadelta+ T cell subsets. From our initial microarray
dataset we observed that TCRgammadelta+ T-LGL leukemia forms a separate group
when compared with different healthy control TCRgammadelta+ T cell subsets,
correlating best with the healthy TemRA subset. The lowest correlation was seen
with the naive subset. Based on specific comparison between healthy control cells
and TCRgammadelta+ T-LGL leukemia cells we observed up-regulation of survival,
proliferation and hematopoietic system related genes, with a remarkable down
regulation of apoptotic pathway genes. RQ-PCR validation of important genes
representative for the dataset, including apoptosis (XIAP, CASP1, BCLAF1 and
CFLAR), proliferation/development (ID3) and inflammation (CD28, CCR7, CX3CR1 and
IFNG) processes largely confirmed the dysregulation in proliferation and
apoptosis. Based on these expression data we conclude that TCRgammadelta+ T-LGL
leukemia is likely the result of an underlying aberrant molecular mechanisms
leading to increased proliferation and reduced apoptosis.
PMID- 28407009
TI - Treatment coverage rates for refractive error in the National Eye Health survey.
AB - OBJECTIVE: To present treatment coverage rates and risk factors associated with
uncorrected refractive error in Australia. METHODS: Thirty population clusters
were randomly selected from all geographic remoteness strata in Australia to
provide samples of 1738 Indigenous Australians aged 40 years and older and 3098
non-Indigenous Australians aged 50 years and older. Presenting visual acuity was
measured and those with vision loss (worse than 6/12) underwent pinhole testing
and hand-held auto-refraction. Participants whose corrected visual acuity
improved to be 6/12 or better were assigned as having uncorrected refractive
error as the main cause of vision loss. The treatment coverage rates of
refractive error were calculated (proportion of participants with refractive
error that had distance correction and presenting visual acuity better than
6/12), and risk factor analysis for refractive correction was performed. RESULTS:
The refractive error treatment coverage rate in Indigenous Australians of 82.2%
(95% CI 78.6-85.3) was significantly lower than in non-Indigenous Australians
(93.5%, 92.0-94.8) (Odds ratio [OR] 0.51, 0.35-0.75). In Indigenous participants,
remoteness (OR 0.41, 0.19-0.89 and OR 0.55, 0.35-0.85 in Outer Regional and Very
Remote areas, respectively), having never undergone an eye examination (OR 0.08,
0.02-0.43) and having consulted a health worker other than an optometrist or
ophthalmologist (OR 0.30, 0.11-0.84) were risk factors for low coverage. On the
other hand, speaking English was a protective factor (OR 2.72, 1.13-6.45) for
treatment of refractive error. Compared to non-Indigenous Australians who had an
eye examination within one year, participants who had not undergone an eye
examination within the past five years (OR 0.08, 0.03-0.21) or had never been
examined (OR 0.05, 0.10-0.23) had lower coverage. CONCLUSION: Interventions that
increase integrated optometry services in regional and remote Indigenous
communities may improve the treatment coverage rate of refractive error.
Increasing refractive error treatment coverage rates in both Indigenous and non
Indigenous Australians through at least five-yearly eye examinations and the
provision of affordable spectacles will significantly reduce the national burden
of vision loss in Australia.
PMID- 28407010
TI - Comparative molecular cytogenetic characterization of seven Deschampsia (Poaceae)
species.
AB - The genus Deschampsia P. Beauv (Poaceae) involves a group of widespread
polymorphic species. Some of them are highly tolerant to stressful and variable
environmental conditions, and D. antarctica is one of the only two vascular
plants growing in Antarctic. This species is a source of useful for selection
traits and a valuable model for studying an environmental stress tolerance in
plants. Genome diversity and comparative chromosomal phylogeny within the genus
have not been studied yet as karyotypes of most Deschampsia species are poorly
investigated. We firstly conducted a comparative molecular cytogenetic analysis
of D. antarctica (Antarctic Peninsula) and related species from various
localities (D. cespitosa, D. danthonioides, D. elongata, D. flexuosa (= Avenella
flexuosa), D. parvula and D. sukatschewii by fluorescence in situ hybridization
with 45S and 5S rDNA, DAPI-banding and sequential rapid in situ hybridization
with genomic DNA of D. antarctica, D. cespitosa, and D. flexuosa. Based on
patterns of distribution of the examined markers, chromosomes of the studied
species were identified. Within these species, common features as well as species
peculiarities in their karyotypic structure and chromosomal distribution of
molecular cytogenetic markers were characterized. Different chromosomal
rearrangements were detected in D. antarctica, D. flexuosa, D. elongata and D.
sukatschewii. In karyotypes of D. antarctica, D. cespitosa, D. elongata and D.
sukatschewii, 0-3 B chromosomes possessed distinct DAPI-bands were observed. Our
findings suggest that the genome evolution of the genus Deschampsia involved
polyploidy and also different chromosomal rearrangements. The obtained results
will help clarify the relationships within the genus Deschampsia, and can be a
basis for the further genetic and biotechnological studies as well as for
selection of plants tolerant to extreme habitats.
PMID- 28407011
TI - Anthracyclines induce early changes in left ventricular systolic and diastolic
function: A single centre study.
AB - AIMS: 2 dimensional (2D) strain analysis detects subclinical left ventricular
(LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and
diastolic function in breast cancer patients early after anthracycline
chemotherapy, and to identify predisposing factors. METHODS AND RESULTS: 140
patients were assessed by detailed echocardiography before and within seven days
post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS),
strain rate and radial and circumferential strain were assessed. Additionally,
left atrial volumes and LV diastolic parameters were evaluated. LVEF although
reduced after treatment, remained within the normal range (60+/-3% vs. 59+/-3%, p
= 0.04). Triplane GLS was significantly reduced after treatment (-20.0+/-1.6% vs.
-19.1+/-1.8%, p<0.001). Subclinical LV dysfunction (>11% reduction in GLS
compared to before therapy) occurred in 22% (29/135). Impaired diastolic function
grade significantly increased from 46% to 57% (p<0.001) after treatment.
Furthermore, diastolic dysfunction was more common in the subgroup group with
reduced systolic GLS compared to those without changes in GLS (30% vs. 11%; p =
0.04). No risk factors or clinical parameters were associated with the
development of subclinical LV dysfunction; however the percentage change in early
diastolic strain rate and the E velocity were independent predictors of >11%
reduction in GLS. CONCLUSION: Twenty two percent of patients had subclinical LV
dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating
that GLS is more sensitive for detection of subclinical LV systolic dysfunction
immediately after anthracycline therapy. Diastolic dysfunction increased,
particularly in the group with reduced GLS, demonstrating the close
pathophysiological relationship between systolic and diastolic function.
PMID- 28407012
TI - Relation between macular morphology and treatment frequency during twelve months
with ranibizumab for diabetic macular edema.
AB - PURPOSE: To investigate whether baseline optical coherence tomography (OCT)
parameters can predict the treatment frequency of intravitreal ranibizumab (IVR)
injections during the first year in patients with diabetic macular edema (DME)
treated with pro re nata (PRN) IVR injections. METHODS: We retrospectively
reviewed 68 eyes of 63 patients with center-involved DME who received IVR
injections for 12 months or longer according to three monthly IVR injections
followed by the PRN dosing. We measured the mean retinal thicknesses in the
individual subfields of the Early Treatment Diabetic Retinopathy Study grid and
evaluated the qualitative and quantitative parameters on OCT sectional images. We
investigated the relationship between these OCT parameters at baseline and the
number of IVR injections during the 12-month follow-up. RESULTS: Three loading
doses were administered to 10 eyes; four to seven annualized IVR injections were
administered to 34 eyes. The number of eyes that received IVR injections
decreased gradually until month 6 and was almost constant from months 7 to 11. No
relationships were seen between the treatment frequency and baseline systemic
factors and the ophthalmic examination findings. Univariate analyses showed that
the number of IVR injections during the first year was associated with the mean
retinal thickness in the individual subfields and the transverse length of the
disrupted external limiting membrane (ELM) and ellipsoid zone of the
photoreceptors. Multivariate analysis showed a significant association with the
thickness in the inferior subfield alone. The treatment frequency during the 12
month follow-up was not correlated with improved visual acuity but was associated
with the decrease in the central subfield thickness and disrupted ELM.
CONCLUSION: The retinal thickness in the inferior subfield predicts the treatment
frequency during the first year in eyes with DME treated with PRN IVR injections.
PMID- 28407013
TI - Dietary resilience among hunter-gatherers of Tierra del Fuego: Isotopic evidence
in a diachronic perspective.
AB - The native groups of Patagonia have relied on a hunter-gatherer economy well
after the first Europeans and North Americans reached this part of the world. The
large exploitation of marine mammals (i.e., seals) by such allochthonous groups
has had a strong impact on the local ecology in a way that might have forced the
natives to adjust their subsistence strategies. Similarly, the introduction of
new foods might have changed local diet. These are the premises of our isotopic
based analysis. There is a large set of paleonutritional investigations through
isotopic analysis on Fuegians groups, however a systematic exploration of food
practices across time in relation to possible pre- and post-contact changes is
still lacking. In this paper we investigate dietary variation in hunter-gatherer
groups of Tierra del Fuego in a diachronic perspective, through measuring the
isotopic ratio of carbon (?13C) and nitrogen (?15N) in the bone collagen of human
and a selection of terrestrial and marine animal samples. The data obtained
reveal an unexpected isotopic uniformity across prehistoric and recent groups,
with little variation in both carbon and nitrogen mean values, which we interpret
as the possible evidence of resilience among these groups and persistence of
subsistence strategies, allowing inferences on the dramatic contraction (and
extinction) of Fuegian populations.
PMID- 28407014
TI - Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in
Mycoplasma genitalium in five cities in Russia and Estonia.
AB - BACKGROUND AND OBJECTIVE: Resistance in the sexually transmitted bacterium
Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly
emerged. However, to date, internationally reported resistance surveillance data
for M. genitalium strains circulating in Eastern Europe are entirely lacking. The
aim of this study was to estimate the prevalence of macrolide and fluoroquinolone
resistance-associated mutations in M. genitalium in four cities in Russia and one
in Estonia, 2013-2016. MATERIALS AND METHODS: Consecutive urogenital samples
found positive for M. genitalium during diagnostic testing were retrospectively
analyzed for resistance-associated mutations in the 23S rRNA and parC genes using
pyrosequencing and conventional Sanger sequencing, respectively. RESULTS: In
total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide
resistance-associated mutations were detected in 4.6% of the samples from Russia
(0.7-6.8% in different cities) and in 10% of the samples from Estonia. The
mutations A2059G and A2058G were highly predominating in both Russia and Estonia,
accounting together for 90.9% of the cases positive for nucleotide substitutions
in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated
mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia.
The mutations S83I and S83N were the most frequent ones in Russia (24.4% each),
whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone
resistance-associated mutations). Approximately 1% of the samples in both
countries harbored both macrolide and possible fluoroquinolone resistance
associated mutations, with A2058G and S83I being the most frequent combination
(37.5%). CONCLUSIONS: The prevalence of macrolide and fluoroquinolone resistance
associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia,
and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of
macrolide and fluoroquinolone resistance in these countries, antimicrobial
resistance surveillance and testing for resistance-associated mutations in M.
genitalium positive cases would be valuable.
PMID- 28407015
TI - Parkinson's disease-associated genetic variation is linked to quantitative
expression of inflammatory genes.
AB - Genome-wide association studies (GWAS) have linked dozens of single nucleotide
polymorphisms (SNPs) with Parkinson's disease (PD) risk. Ascertaining the
functional and eventual causal mechanisms underlying these relationships has
proven difficult. The majority of risk SNPs, and nearby SNPs in linkage
disequilibrium (LD), are found in intergenic or intronic regions and confer risk
through allele-dependent expression of multiple unknown target genes. Combining
GWAS results with publicly available GTEx data, generated through eQTL
(expression quantitative trait loci) identification studies, enables a direct
association of SNPs to gene expression levels and aids in narrowing the large
population of potential genetic targets for hypothesis-driven experimental cell
biology. Separately, overlapping of SNPs with putative enhancer segmentations can
strengthen target filtering. We report here the results of analyzing 7,607 PD
risk SNPs along with an additional 23,759 high linkage disequilibrium-associated
variants paired with eQTL gene expression. We found that enrichment analysis on
the set of genes following target filtering pointed to a single large LD block at
6p21 that contained multiple HLA-MHC-II genes. These MHC-II genes remain
associated with PD when the genes were filtered for correlation between GWAS
significance and eQTL levels, strongly indicating a direct effect on PD etiology.
PMID- 28407016
TI - Learning from label proportions in brain-computer interfaces: Online unsupervised
learning with guarantees.
AB - OBJECTIVE: Using traditional approaches, a brain-computer interface (BCI)
requires the collection of calibration data for new subjects prior to online use.
Calibration time can be reduced or eliminated e.g., by subject-to-subject
transfer of a pre-trained classifier or unsupervised adaptive classification
methods which learn from scratch and adapt over time. While such heuristics work
well in practice, none of them can provide theoretical guarantees. Our objective
is to modify an event-related potential (ERP) paradigm to work in unison with the
machine learning decoder, and thus to achieve a reliable unsupervised
calibrationless decoding with a guarantee to recover the true class means.
METHOD: We introduce learning from label proportions (LLP) to the BCI community
as a new unsupervised, and easy-to-implement classification approach for ERP
based BCIs. The LLP estimates the mean target and non-target responses based on
known proportions of these two classes in different groups of the data. We
present a visual ERP speller to meet the requirements of LLP. For evaluation, we
ran simulations on artificially created data sets and conducted an online BCI
study with 13 subjects performing a copy-spelling task. RESULTS: Theoretical
considerations show that LLP is guaranteed to minimize the loss function similar
to a corresponding supervised classifier. LLP performed well in simulations and
in the online application, where 84.5% of characters were spelled correctly on
average without prior calibration. SIGNIFICANCE: The continuously adapting LLP
classifier is the first unsupervised decoder for ERP BCIs guaranteed to find the
optimal decoder. This makes it an ideal solution to avoid tedious calibration
sessions. Additionally, LLP works on complementary principles compared to
existing unsupervised methods, opening the door for their further enhancement
when combined with LLP.
PMID- 28407018
TI - Correction: Detrimental ELAVL-1/HuR-dependent GSK3beta mRNA stabilization impairs
resolution in acute respiratory distress syndrome.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172116.].
PMID- 28407017
TI - Characterizing the anti-inflammatory and tissue protective actions of a novel
Annexin A1 peptide.
AB - Inflammation in now appreciated to be at the centre of may diseases that affect
Western civilization. Current therapeutics for managing these conditions may
interfere with the host response leading to immune suppression. We recently
developed an annexin (Anx) A1-derived peptide, coined CR-AnxA12-50, which
displays potent pro-resolving and tissue protective actions. Herein, we designed
a novel peptide using CR-AnxA12-50 as a template that was significantly more
resistant to neutrophil-mediated degradation. This peptide, termed CR-AnxA12-48,
retained high affinity and specificity to the pro-resolving Lipoxin A4 receptor
(ALX) with an IC50 of ~20nM. CR-AnxA12-48 dose dependently (100fM-10nM) promoted
the efferocytosis of apoptotic neutrophils, an action that was mediated by the
murine orthologue of human ALX. The neutrophil-directed actions were also
retained with human primary cells were CR-AnxA12-48 reduced human neutrophil
recruitment to activated endothelial cells at concentrations as low as 100 pM.
This protective action was mediated by human ALX, since incubation of neutrophils
with an anti-ALX antibody reversed this anti-inflammatory actions of CR-AnxA12
48. Administration of this peptide to mice during dermal inflammation led to a
significant and dose dependent decrease in neutrophil recruitment. This reduction
in neutrophil numbers was more pronounced than that displayed by the parent
peptide CR-AnxA12-50. CR-AnxA12-48 was also cardioprotecitve reducing infarct
size and systemic chemokine (C-C motif) ligand 5 concentration following ischemia
reperfusion injury. These findings identify CR-AnxA12-48 as a new ALX agonist
that regulates phagocyte responses and displays tissue-protective actions.
PMID- 28407019
TI - Comparison between titanium mesh and autogenous iliac bone graft to restore
vertebral height through posterior approach for the treatment of thoracic and
lumbar spinal tuberculosis.
AB - OBJECT: To compare the clinical efficacy of titanium mesh cages and autogenous
iliac bone graft to restore vertebral height through posterior approach in
patients with thoracic and lumbar spinal tuberculosis. METHOD: 59 patients with
spinal tuberculosis underwent interbody fusion and internal fixation through
posterior approach in our department from January 2011 to December 2013. In group
A, 34 patients obtained titanium mesh for the reconstruction of vertebral height,
among them 25 patients (group A1) suffered from single-segment spinal
tuberculosis, and 9 patients, (group A2) had multi-segment spinal tuberculosis.
In group B, 25 patients got autogenous iliac bone graft to restore vertebral
height, including 24 patients with single-segment spinal tuberculosis (group B1),
and 1 patient with multi-segment spinal tuberculosis (group B2). The clinical
efficacy was evaluated based on average operation time, blood loss, hospital
stays, hospitalization expenses, visual analog scale (VAS), Oswestry Disability
Index (ODI), erythrocyte sedimentation rate (ESR), C-Reactive protein (CRP),
neurological function recovery, bony fusion, intervertebral height, Cobb angle
and postoperative complications. RESULTS: Final follow-up time was an average of
35.5 months ranging from 15 to 56 months. All patients were completely cured and
obtained solid bone fusion. The bony fusion time was 9.4+/-6.1 months in group
A1, 10.2+/-2.7 months in group A2 and 8.7+/-3.6 months in group B1. There were no
significant difference among three groups (P>0.05). The Cobb correction and
restoration of intervertebral height significantly improved compared with those
in preoperation, but without significant difference among three groups (P>0.05).
The loss of angular correction and intervertebral height in group A1 were found
to be less than those in group B1 (P<0.05), but with no significant difference
between group A1 and group A2, and between group A2 and group B1 (P>0.05).
Patients in group B1 got the most loss of angular correction and intervertebral
height. In addition, neurological function was revealed to be significantly
improved after surgery. There were significant differences of VAS, ODI, ESR and
CRP between preoperation and postoperation at the final follow-up time (P<0.05),
with no significant difference among three groups (P>0.05). No statistically
significant difference was found when analyzing blood loss, hospital stays,
hospitalization expenses, and corrective cost among three groups (P>0.05).
Complications included cerebrospinal fluid leakage (2 cases in group A1 and group
A2), sinus formation (3 cases in group A1, group A2 and group B1), and
intervertebral infection (1 case in group B1), but no implant failure or donor
site complications was found in any patient. CONCLUSIONS: Titanium mesh cages
could obtain good clinical efficacy comparable to autogenous iliac bone graft
when treating single-segment spinal tuberculosis, and may be better than
autogenous iliac bone graft for treating multi-segment spinal tuberculosis.
PMID- 28407020
TI - Mortality after out-of-hospital cardiac arrest in a Spanish Region.
AB - AIMS: To determine out-of-hospital cardiac arrest mortality in the province of
Alicante (Spain) and its associated factors. METHODS: Cross-sectional
observational study of all patients who received cardiopulmonary resuscitation
(CPR) by the Emergency Medical Services (EMS) (n = 422) in the province of
Alicante in 2013. To determine associated factors, a binary logistic regression
model was constructed. Primary outcome: death before arriving at the hospital.
Predictive variables: gender, age, artificial respiration, prior functional
status, asystole, cardiogenic aetiology, bystander CPR, time from the cardiac
arrest to the arrival of the EMS and location of cardiac arrest. RESULTS: There
were 337 deaths (79.9%; 95% CI: 76.0-83.7%). Factors independently associated
(p<0.05) with death were: male gender (OR = 2.11; 95% CI: 1.20-3.72; p = 0.010),
asystole (OR = 1.99, 95% CI: 1.17-3.39; p = 0.012), cardiac arrest at home (OR =
2.44; 95% CI: 1.42-4.18; p = 0.001) and an increased time between arrest and EMS
arrival (OR = 1.05, 95% CI: 1.01-1.09, p = 0.009). Having a worse prior
functional status had a tendency towards significance (OR = 0.56, 95% CI: 0.31
1.02, p = 0.059). CONCLUSIONS: Mortality was high. The associated factors were:
male gender, asystole, worse prior functional status, longer time from the
cardiac arrest to the arrival of the EMS and having the cardiac arrest at home.
The clearly negative impact of experiencing a cardiac arrest at home necessitates
modifying training policies in Spain. These policies should be focused on
providing information about CPR in schools in order to decrease the mortality of
these events.
PMID- 28407021
TI - Analysis of the prevalence and associated factors of overactive bladder in adult
Korean men.
AB - Overactive bladder (OAB) is a prevalent condition characterized by lower urinary
tract symptoms (LUTS). Age, education, income, marital status, sleep, and
emotional problems have been associated with OAB; however, conflicting results
exist. The present study was conducted to estimate the prevalence of OAB and
comprehensively analyze its associated factors in a large cross-sectional,
population-based study. The data of 94,554 participants aged 19-107 were analyzed
from the Korean Community Health Survey (KCHS) of 2012. Data on marital status,
physical activity, education level, occupation, body mass index (BMI), income
level, sleep time, and stress level were retrieved for all enrolled participants.
The overactive bladder symptom score (OABSS) was used to evaluate the presence
and degree of OAB. Simple and multiple logistic regression analyses with complex
sampling were used for the associations between various factors and the presence
of OAB. Overall, OAB was present in approximately 2.9% of the participants. The
prevalence of OAB increased with age and steeply increased after 60 years of age
(adjusted odds ratio [AOR] for each 10 years = 1.70, 95% confidence interval [CI]
= 1.61-1.80, P<0.001). The prevalence of OAB was lower in married than unmarried
subjects (AOR = 0.59, 95% CI = 0.48-0.72, P<0.001). The prevalence of OAB was
significantly different according to occupation Compared to manager, expert,
specialist, clerk group, the prevalence of OAB was highest in unemployed group
(AOR = 1.90, 95% CI = 1.55-2.32, P < 0.001). Being underweight was correlated
with OAB (AOR = 1.29, 95% CI = 1.08-1.55, P = 0.018). Inadequate sleep showed a
significant association with OAB (AOR = 1.13, 95% CI = 1.02-1.25 for <=6 hours of
sleep time and AOR = 1.53, 95% CI = 1.27-1.86 for >=9 hours of sleep, P<0.001).
Stress level showed a dose-dependent positive association with OAB [AOR (95% CI)
= 3.91 (3.13-4.89) > 2.16 (1.88-2.48) > 1.39 (1.23-1.57) for severe stress >
moderate stress > some stress, respectively, P<0.001]. A medical history of
diabetes mellitus, hyperlipidemia, and/or cerebral stroke was significantly
related to OAB. Approximately 2.9% of adult Korean men experienced OAB based on
the OABSS. Unmarried status; occupation; being underweight; inadequate sleep;
stress; and medical history of diabetes mellitus, hyperlipidemia, or cerebral
stroke were significantly correlated with OAB.
PMID- 28407022
TI - Gap analysis on the biology of Mediterranean marine fishes.
AB - We estimated the current level of knowledge concerning several biological
characteristics of the Mediterranean marine fishes by carrying out a gap analysis
based on information extracted from the literature, aiming to identify research
trends and future needs in the field of Mediterranean fish biology that can be
used in stock assessments, ecosystem modeling and fisheries management. Based on
the datasets that emerged from the literature review, there is no information on
any biological characteristic for 43% (n = 310) of the Mediterranean fish
species, whereas for an additional 15% (n = 109) of them there is information
about just one characteristic. The gap between current and desired knowledge
(defined here as having information on most biological characteristics for at
least half of the Mediterranean marine fishes) is smaller in length-weight
relationships, which have been studied for 43% of the species, followed by
spawning (39%), diet (29%), growth (25%), maturity (24%), lifespan (19%) and
fecundity (17%). The gap is larger in natural mortality for which information is
very scarce (8%). European hake (Merluccius merluccius), red mullet (Mullus
barbatus), annular seabream (Diplodus annularis), common pandora (Pagellus
erythrinus), European anchovy (Engraulis encrasicolus), European pilchard
(Sardina pilchardus) and bogue (Boops boops) were the most studied species, while
sharks and rays were among the least studied ones. Only 25 species were fully
studied, i.e. there was available information on all their biological
characteristics. The knowledge gaps per characteristic varied among the western,
central and eastern Mediterranean subregions. The number of available records per
species was positively related to total landings, while no relationship emerged
with its maximum reported length, trophic level and commercial value. Future
research priorities that should be focused on less studied species (e.g. sharks
and rays) and mortality/fecundity instead of length-weight relationships, as well
as the economy of scientific sampling (using the entire catch to acquire data on
as many biological characteristics as possible) are discussed.
PMID- 28407023
TI - Ten simple rules for making research software more robust.
AB - Software produced for research, published and otherwise, suffers from a number of
common problems that make it difficult or impossible to run outside the original
institution or even off the primary developer's computer. We present ten simple
rules to make such software robust enough to be run by anyone, anywhere, and
thereby delight your users and collaborators.
PMID- 28407024
TI - The prognosis of infective endocarditis treated with biological valves versus
mechanical valves: A meta-analysis.
AB - OBJECTIVE: Surgery remains the primary form of treatment for infective
endocarditis (IE). However, it is not clear what type of prosthetic valve
provides a better prognosis. We conducted a meta-analysis to compare the
prognosis of infective endocarditis treated with biological valves to cases
treated with mechanical valves. METHODS: Pubmed, Embase and Cochrane databases
were searched from January 1960 to November 2016.Randomized controlled trials,
retrospective cohorts and prospective studies comparing outcomes between
biological valve and mechanical valve management for infective endocarditis were
analyzed. The Newcastle-Ottawa Scale(NOS) was used to evaluate the quality of the
literature and extracted data, and Stata 12.0 software was used for the meta
analysis. RESULTS: A total of 11 publications were included; 10,754 cases were
selected, involving 6776 cases of biological valves and 3,978 cases of mechanical
valves. The all-cause mortality risk of the biological valve group was higher
than that of the mechanical valve group (HR = 1.22, 95% CI 1.03 to 1.44, P =
0.023), as was early mortality (RR = 1.21, 95% CI 1.02 to 1.43, P = 0.033). The
recurrence of endocarditis (HR = 1.75, 95% CI 1.26 to 2.42, P = 0.001), as well
as the risk of reoperation (HR = 1.79, 95% CI 1.15 to 2.80, P = 0.010) were more
likely to occur in the biological valve group. The incidence of postoperative
embolism was less in the biological valve group than in the mechanical valve
group, but this difference was not statistically significant (RR = 0.90, 95% CI
0.76 to 1.07, P = 0.245). For patients with prosthetic valve endocarditis (PVE),
there was no significant difference in survival rates between the biological
valve group and the mechanical valve group (HR = 0.91, 95% CI 0.68 to 1.21, P =
0.520). CONCLUSION: The results of our meta-analysis suggest that mechanical
valves can provide a significantly better prognosis in patients with infective
endocarditis. There were significant differences in the clinical features of
patients receiving a biological valve compared to patients receiving a mechanical
valve. A large, multicenter retrospective study included in our meta-analysis
suggested that any mortality risk of the biological valve group was significant
higher than that of the mechanical valve group. However, the risk was no
different after risk was adjusted. So, we thought the reason for this result may
be related to the characteristics of the patient rather than valve dysfunction.
It is still necessary to future randomized studies to verify this conclusion.
PMID- 28407025
TI - Relationships between temperaments, occupational stress, and insomnia among
Japanese workers.
AB - Insomnia among workers reduces the quality of life, contributes toward the
economic burden of healthcare costs and losses in work performance. The
relationship between occupational stress and insomnia has been reported in
previous studies, but there has been little attention to temperament in
occupational safety and health research. The aim of this study was to clarify the
relationships between temperament, occupational stress, and insomnia. The
subjects were 133 Japanese daytime local government employees. Temperament was
assessed using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego
Auto questionnaire (TEMPS-A). Occupational stress was assessed using the Generic
Job Stress Questionnaire (GJSQ). Insomnia was assessed using the Athens Insomnia
Scale (AIS). Stepwise multiple logistic regression analyses were conducted. In a
stepwise multivariate logistic regression analysis, it was found that the higher
subdivided stress group by "role conflict" (OR = 5.29, 95% CI, 1.61-17.32) and
anxious temperament score (OR = 1.33; 95% CI, 1.19-1.49) was associated with the
presence of insomnia using an adjusted model, whereas other factors were excluded
from the model. The study limitations were the sample size and the fact that only
Japanese local government employees were surveyed. This study demonstrated the
relationships between workers' anxious temperament, role conflict, and insomnia.
Recognizing one's own anxious temperament would lead to self-insight, and the
recognition of anxious temperament and reduction of role conflict by their
supervisors or coworkers would reduce the prevalence of insomnia among workers in
the workplace.
PMID- 28407026
TI - Streptococcal Adhesin P (SadP) contributes to Streptococcus suis adhesion to the
human intestinal epithelium.
AB - BACKGROUND: Streptococcus suis is a zoonotic pathogen, causing meningitis and
septicemia. We previously demonstrated that the gastrointestinal tract (GIT) is
an entry site for zoonotic S. suis infection. Here we studied the contribution of
Streptococcal adhesin Protein (SadP) to host-pathogen interaction at GIT level.
METHODS: SadP expression in presence of Intestinal Epithelial Cells (IEC) was
compared with expression of other virulence factors by measuring transcript
levels using quantitative Real Time PCR (qRT-PCR). SadP variants were identified
by phylogenetic analysis of complete DNA sequences. The interaction of SadP
knockout and complementation mutants with IEC was tested in vitro. RESULTS:
Expression of sadP was significantly increased in presence of IEC. Sequence
analysis of 116 invasive strains revealed five SadP sequence variants,
correlating with genotype. SadP1, present in zoonotic isolates of clonal complex
1, contributed to binding to both human and porcine IEC and translocation across
human IEC. Antibodies against the globotriaosylceramide Gb3/CD77 receptor
significantly inhibited adhesion to human IEC. CONCLUSION: SadP is involved in
the host-pathogen interaction in the GIT. Differences between SadP variants may
determine different affinities to the Gb3/CD77 host-receptor, contributing to
variation in adhesion capacity to host IEC and thus to S. suis zoonotic
potential.
PMID- 28407027
TI - An efficient depth map preprocessing method based on structure-aided domain
transform smoothing for 3D view generation.
AB - Depth image-based rendering (DIBR), which is used to render virtual views with a
color image and the corresponding depth map, is one of the key techniques in the
2D to 3D conversion process. Due to the absence of knowledge about the 3D
structure of a scene and its corresponding texture, DIBR in the 2D to 3D
conversion process, inevitably leads to holes in the resulting 3D image as a
result of newly-exposed areas. In this paper, we proposed a structure-aided depth
map preprocessing framework in the transformed domain, which is inspired by
recently proposed domain transform for its low complexity and high efficiency.
Firstly, our framework integrates hybrid constraints including scene structure,
edge consistency and visual saliency information in the transformed domain to
improve the performance of depth map preprocess in an implicit way. Then,
adaptive smooth localization is cooperated and realized in the proposed framework
to further reduce over-smoothness and enhance optimization in the non-hole
regions. Different from the other similar methods, the proposed method can
simultaneously achieve the effects of hole filling, edge correction and local
smoothing for typical depth maps in a united framework. Thanks to these
advantages, it can yield visually satisfactory results with less computational
complexity for high quality 2D to 3D conversion. Numerical experimental results
demonstrate the excellent performances of the proposed method.
PMID- 28407028
TI - CHD1: a new treatment biomarker for recombination deficiency in castration
resistant prostate cancer?
PMID- 28407029
TI - Shiraz Verbal Learning Test (SVLT): Normative Data for Neurologically Intact
Speakers of Persian.
AB - Objective: Memory assessment plays an important role in the diagnosis of
neurodegenerative disorders. Several tests, such as the California Verbal
Learning Test (CVLT), have been developed for this purpose, yet a variety of
different factors can affect one's performance on such tests, the most important
of which are demographic and cultural variables. The present study examined the
norming process performed on the CVLT-revised and aimed to devise a new test, the
Shiraz Verbal Learning Test (SVLT), to better meet the needs of speakers of
Persian. Method: In order to collect normative data, a group of 1275 Persian
speaking individuals consisting of both sexes (676 women and 599 men) aged 20-89
years old were selected for this study. Results: The results of Pearson's
Correlation analysis indicated that there was a significant negative correlation
between age and SVLT performance and a positive one between education and SVLT
performance (p < .001) among the whole sample. Moreover, between-group analyses
showed that the female participants performed significantly better than their
male counterparts on nearly all subtests (Total Trails 1-5, Short-Delay Free
Recall, Short-Delay Cued Recall, Long-Delay Free Recall, Long-Delay Cued Recall,
and Total Learning Slope), with the only exception being Long-Delay Yes/No
Recognition. Conclusions: These results suggest that the SVLT has the potential
to be further developed among different culture and language groups. This test
can also be used for clinical and research purposes for patients with
neuropsychiatric disorders who need further neuropsychological assessment.
PMID- 28407030
TI - Intratumoral heterogeneity: pathways to treatment resistance and relapse in human
glioblastoma.
AB - Intratumoral heterogeneity (ITH) has increasingly being described for multiple
cancers as the root cause of therapy resistance. Recent studies have started to
explore the scope of ITH in glioblastoma (GBM), a highly aggressive and fatal
form of brain tumor, to explain its inevitable therapy resistance and disease
relapse. In this review, we detail the emerging data that explores the extensive
genetic, cellular and functional ITH present in GBM. We discuss current
experimental models of human GBM recurrence and suggest harnessing new
technologies (CRISPR-Cas9 screening, CyTOF, cellular barcoding, single cell
analysis) to delineate GBM ITH and identify treatment-refractory cell
populations, thus opening new therapeutic windows. We will also explore why
current therapeutics have failed in clinical trials and how ITH can inform us on
developing empiric therapies for the treatment of recurrent GBM.
PMID- 28407031
TI - Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1
immunotherapy.
PMID- 28407032
TI - Toll-like receptor 5 agonist CBLB502 induces radioprotective effects in vitro.
AB - CBLB502 derived from Salmonella flagellin is a novel agonist of Toll-like
receptor 5 (TLR5). It has been shown that CBLB502 can exert high radioprotective
efficacy on mice and primates from both GI and hematopoietic syndromes during
whole-body irradiation with low toxicity and immunogenicity. However, no
effective system has been used to investigate the protective effect of CBLB502
against irradiation and the related mechanism in vitro. In this study, we
investigated the radioprotective properties of CBLB502 in HEK293-N-T cells
constitutively expressing human TLR5 and NF-kappaB-dependent luciferase. HEK293-N
T cells were treated with different doses of CBLB502 prior to 60Co-gamma ray
irradiation. After irradiation, cell viability was real-time measured for 4 days
by using the real-time cell analysis system. We found that CBLB502 was capable of
efficiently maintaining the survival rate of irradiated HEK293-N-T cells. Then
apoptotic cell death and cell cycle were detected by flow cytometry. The results
showed that CBLB502 pre-treatment could reduce the apoptosis and promote the
recovery of irradiated HEK293-N-T cells from G2-phase arrest in a dose-dependent
manner. Our data indicated that CBLB502 has a direct radioprotective effect in
vitro via anti-apoptosis and promotes cell cycle recovery. The method developed
here could be an effective in vitro system to screen other TLR5-target
radioprotectants like CBLB502.
PMID- 28407033
TI - BioCIDER: a Contextualisation InDEx for biological Resources discovery.
AB - Summary: The vast, uncoordinated proliferation of bioinformatics resources
(databases, software tools, training materials etc.) makes it difficult for users
to find them. To facilitate their discovery, various services are being developed
to collect such resources into registries. We have developed BioCIDER, which,
rather like online shopping 'recommendations', provides a contextualization index
to help identify biological resources relevant to the content of the sites in
which it is embedded. Availability and Implementation: BioCIDER
(www.biocider.org) is an open-source platform. Documentation is available online
(https://goo.gl/Klc51G), and source code is freely available via GitHub
(https://github.com/BioCIDER). The BioJS widget that enables websites to embed
contextualization is available from the BioJS registry (http://biojs.io/). All
code is released under an MIT licence. Contact: carlos.horro@earlham.ac.uk or
rafael.jimenez@elixir-europe.org or manuel@repositive.io.
PMID- 28407034
TI - Network module-based model in the differential expression analysis for RNA-seq.
AB - Motivation: RNA-seq has emerged as a powerful technology for the detection of
differential gene expression in the transcriptome. The commonly used statistical
methods for RNA-seq differential expression analysis were designed for individual
genes, which may detect too many irrelevant significantly genes or too few genes
to interpret the phenotypic changes. Recently network module-based methods have
been proposed as a powerful approach to analyze and interpret expression data in
microarray and shotgun proteomics. But the module-based statistical model has not
been adequately addressed for RNA-seq data. Result: we proposed a network module
based generalized linear model for differential expression analysis of the count
based sequencing data from RNA-seq. The simulation studies demonstrated the
effectiveness of the proposed model and the improvement of the statistical power
for identifying the differentially expressed modules in comparison to the
existing methods. We also applied our method to tissue datasets and identified
207 significantly differentially expressed kidney-active or liver-active modules.
For liver cancer datasets, significantly differentially expressed modules,
including Wnt signaling pathway and VEGF pathway, were found to be tightly
associated with liver cancer. Besides, in comparison with the single gene-level
analysis, our method could identify more significantly biological modules, which
related to the liver cancer. Availability and Implementation: The R package
SeqMADE is available at https://cran.r-project.org/web/packages/SeqMADE/ .
Contact: jing.li@sjtu.edu.cn. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28407035
TI - IcyTree: rapid browser-based visualization for phylogenetic trees and networks.
AB - Summary: IcyTree is an easy-to-use application which can be used to visualize a
wide variety of phylogenetic trees and networks. While numerous phylogenetic tree
viewers exist already, IcyTree distinguishes itself by being a purely online
tool, having a responsive user interface, supporting phylogenetic networks
(ancestral recombination graphs in particular), and efficiently drawing trees
that include information such as ancestral locations or trait values. IcyTree
also provides intuitive panning and zooming utilities that make exploring large
phylogenetic trees of many thousands of taxa feasible. Availability and
Implementation: IcyTree is a web application and can be accessed directly at
http://tgvaughan.github.com/icytree . Currently supported web browsers include
Mozilla Firefox and Google Chrome. IcyTree is written entirely in client-side
JavaScript (no plugin required) and, once loaded, does not require network access
to run. IcyTree is free software, and the source code is made available at
http://github.com/tgvaughan/icytree under version 3 of the GNU General Public
License. Contact: tgvaughan@gmail.com.
PMID- 28407036
TI - The clinical impact of an EML4-ALK variant on survival following crizotinib
treatment in patients with advanced ALK-rearranged non-small-cell lung cancer.
PMID- 28407037
TI - What Explains Socioeconomic Differences in the Speed of Heart Rate Recovery to
Postural Challenge?
AB - Background: Much recent work has focused on the value of heart rate recovery
(HRR) as a marker of cardiovascular health and a predictor of mortality. This
article explores socioeconomic variation in HRR following exposure to a potent
physiological stressor. Methods: The sample involved a nationally representative
cohort of 4,475 community-dwelling older persons aged 50 years and older
participating in the Irish Longitudinal Study on Ageing (TILDA). Participants
completed an active stand (ie, vertical stand from a supine position) as part of
a detailed clinic-based cardiovascular health assessment. Beat-to-beat HRR to
standing was monitored over a 2-minute time horizon using a finometer. Highest
level of educational achievement served as the indicator variable for
socioeconomic status and mediation analysis was undertaken to explore the
pathways through which social inequality comes to affect the speed of HRR using
the extensive array of covariates available in TILDA. Results: Participants with
primary level education were characterized by a significantly slower HRR after
standing compared with the tertiary educated (B = -1.15 bpm, CI95 = -1.78, -0.52;
p < .001). Mediation analysis revealed that lifetime smoking accounted for a
sizeable proportion (40.4%) of the educational differential. Adjustment for other
objectively measured markers of lifestyle measured during the clinic visit
accounted for only a small proportion (5.2%) of the difference. Discussion:
Smoking may represent a major pathway through which the social environment
becomes biologically embedded in the tissues and organs of the body precipitating
earlier vascular ageing among more socially disadvantaged groups, emphasizing the
need to address the causes of these inequalities.
PMID- 28407038
TI - emMAW: computing minimal absent words in external memory.
AB - Motivation: The biological significance of minimal absent words has been
investigated in genomes of organisms from all domains of life. For instance,
three minimal absent words of the human genome were found in Ebola virus genomes.
There exists an O(n) -time and O(n) -space algorithm for computing all minimal
absent words of a sequence of length n on a fixed-sized alphabet based on suffix
arrays. A standard implementation of this algorithm, when applied to a large
sequence of length n , requires more than 20 n bytes of RAM. Such memory
requirements are a significant hurdle to the computation of minimal absent words
in large datasets. Results: We present emMAW, the first external-memory algorithm
for computing minimal absent words. A free open-source implementation of our
algorithm is made available. This allows for computation of minimal absent words
on far bigger data sets than was previously possible. Our implementation requires
less than 3 h on a standard workstation to process the full human genome when as
little as 1 GB of RAM is made available. We stress that our implementation,
despite making use of external memory, is fast; indeed, even on relatively
smaller datasets when enough RAM is available to hold all necessary data
structures, it is less than two times slower than state-of-the-art internal
memory implementations. Availability and implementation:
https://github.com/solonas13/maw (free software under the terms of the GNU GPL).
Contact: alice.heliou@lix.polytechnique.fr or solon.pissis@kcl.ac.uk.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28407039
TI - Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive
non-small-cell lung cancer based on T790M status after disease progression during
EGFR-TKI treatment.
AB - Background: The efficacy of programmed death-1 blockade in epidermal growth
factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC)
patients with different mechanisms of acquired resistance to EGFR tyrosine kinase
inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and
immune-related factors in such patients according to their status for the T790M
resistance mutation of EGFR. Patients and methods: We identified 25 patients with
EGFR mutation-positive NSCLC who were treated with nivolumab after disease
progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD
L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens
obtained after acquisition of EGFR-TKI resistance were determined by
immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to
identify gene alterations. The relation of T790M status to PD-L1 expression or
TIL density was also examined in an independent cohort of 60 patients (cohort B).
Results: In cohort A, median progression-free survival (PFS) was 2.1 and 1.3
months for T790M-negative and T790M-positive patients, respectively (P = 0.099;
hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was
2.1 and 1.3 months for patients with a PD-L1 expression level of >=1% or <1%,
respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10
1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff
values of >=10% and >=50%. The proportion of tumors with a PD-L1 level of >=10%
or >=50% was higher among T790M-negative patients than among T790M-positive
patients of both cohorts A and B. Nivolumab responders had a significantly higher
CD8+ TIL density and nonsynonymous mutation burden. Conclusion: T790M-negative
patients with EGFR mutation-positive NSCLC are more likely to benefit from
nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1
expression level, than are T790M-positive patients.
PMID- 28407040
TI - Experiences of Discrimination and Incident Type 2 Diabetes Mellitus: The Multi
Ethnic Study of Atherosclerosis (MESA).
AB - Experiences of discrimination are associated with increased risk of adverse
health outcomes; however, it is unknown whether discrimination is related to
incident type 2 diabetes mellitus (diabetes). We investigated the associations of
major experiences of discrimination (unfair treatment in 6 situations) and
everyday discrimination (frequency of day-to-day experiences of unfair treatment)
with incident diabetes among 5,310 participants from the Multi-Ethnic Study of
Atherosclerosis, enrolled in 2000-2002. Using Cox proportional hazards models, we
estimated hazard ratios and confidence intervals, adjusting for demographic
factors, depressive symptoms, stress, smoking, alcohol, physical activity, diet,
waist circumference, and body mass index. Over a median follow-up of 9.4 years,
654 diabetes cases were accrued. Major experiences of discrimination were
associated with greater risk of incident diabetes when modeled continuously (for
each additional experience of discrimination, hazard ratio = 1.09, 95% confidence
interval: 1.01, 1.17) or categorically (for >=2 experiences vs. 0, hazard ratio =
1.34, 95% confidence interval: 1.08, 1.66). Similar patterns were observed when
evaluating discrimination attributed to race/ethnicity or to a combination of
other sources. Everyday discrimination was not associated with incident diabetes.
In conclusion, major experiences of discrimination were associated with increased
risk of incident diabetes, independent of obesity or behavioral and psychosocial
factors. Future research is needed to explore the mechanisms of the
discrimination-diabetes relationship.
PMID- 28407042
TI - Incorporating prior information into differential network analysis using non
paranormal graphical models.
AB - Motivation: Understanding how gene regulatory networks change under different
cellular states is important for revealing insights into network dynamics.
Gaussian graphical models, which assume that the data follow a joint normal
distribution, have been used recently to infer differential networks. However,
the distributions of the omics data are non-normal in general. Furthermore,
although much biological knowledge (or prior information) has been accumulated,
most existing methods ignore the valuable prior information. Therefore, new
statistical methods are needed to relax the normality assumption and make full
use of prior information. Results: We propose a new differential network analysis
method to address the above challenges. Instead of using Gaussian graphical
models, we employ a non-paranormal graphical model that can relax the normality
assumption. We develop a principled model to take into account the following
prior information: (i) a differential edge less likely exists between two genes
that do not participate together in the same pathway; (ii) changes in the
networks are driven by certain regulator genes that are perturbed across
different cellular states and (iii) the differential networks estimated from
multi-view gene expression data likely share common structures. Simulation
studies demonstrate that our method outperforms other graphical model-based
algorithms. We apply our method to identify the differential networks between
platinum-sensitive and platinum-resistant ovarian tumors, and the differential
networks between the proneural and mesenchymal subtypes of glioblastoma. Hub
nodes in the estimated differential networks rediscover known cancer-related
regulator genes and contain interesting predictions. Availability and
Implementation: The source code is at https://github.com/Zhangxf-ccnu/pDNA.
Contact: szuouyl@gmail.com. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28407041
TI - Effects of Low Muscle Mass on Albuminuria and Chronic Kidney Disease in Patients
With Type 2 Diabetes: The Korean Sarcopenic Obesity Study (KSOS).
AB - Background: Previous studies have shown that chronic kidney disease (CKD) is
associated with accelerated loss of skeletal muscle in patients on dialysis.
However, the relationships of sarcopenia with albuminuria and early-stage CKD in
patients with type 2 diabetes have not been examined. Methods: We analyzed
diabetic subgroup data from 409 patients with type 2 diabetes from the Korean
Sarcopenic Obesity Study (KSOS). Sarcopenia was defined as a skeletal muscle mass
index (SMI; SMI [%] = total skeletal muscle mass [kg]/weight [kg] * 100) less
than 2 SD below the sex-specific mean for a younger reference group. The
estimated glomerular filtration rates and urinary albumin-to-creatinine ratios
were used to assess renal function and albuminuria. Results: The prevalence of
sarcopenia was significantly increased in the albuminuria group compared with the
normo-albuminuria group (26.7% vs 12.6%, p = .001), as well as in CKD 3 group
compared with the CKD 1-2 group (46.7% vs 15.1%, p = .005). After adjusting for
age, SMI was negatively correlated with urinary albumin-to-creatinine ratios and
positively correlated with aspartate aminotransferase, alanine aminotransferase,
total cholesterol, high-density lipoprotein cholesterol, and low-density
lipoprotein cholesterol levels. Multiple logistic regression analysis revealed
that the odds ratio for albuminuria association was 3.02 (95% CI 1.37-6.67) in
the lowest tertile of SMI compared with the highest tertile after adjusting for
various confounding factors. Conclusions: Sarcopenia is more prevalent in
individuals with albuminuria than in those without albuminuria. Furthermore,
increased albuminuria is independently associated with low muscle mass in
patients with type 2 diabetes.
PMID- 28407043
TI - SubCons: a new ensemble method for improved human subcellular localization
predictions.
AB - Motivation: Knowledge of the correct protein subcellular localization is
necessary for understanding the function of a protein. Unfortunately large-scale
experimental studies are limited in their accuracy. Therefore, the development of
prediction methods has been limited by the amount of accurate experimental data.
However, recently large-scale experimental studies have provided new data that
can be used to evaluate the accuracy of subcellular predictions in human cells.
Using this data we examined the performance of state of the art methods and
developed SubCons, an ensemble method that combines four predictors using a
Random Forest classifier. Results: SubCons outperforms earlier methods in a
dataset of proteins where two independent methods confirm the subcellular
localization. Given nine subcellular localizations, SubCons achieves an F1-Score
of 0.79 compared to 0.70 of the second best method. Furthermore, at a FPR of 1%
the true positive rate (TPR) is over 58% for SubCons compared to less than 50%
for the best individual predictor. Availability and Implementation: SubCons is
freely available as a webserver (http://subcons.bioinfo.se) and source code from
https://bitbucket.org/salvatore_marco/subcons-web-server. The golden dataset as
well is available from http://subcons.bioinfo.se/pred/download. Contact:
arne@bioinfo.se. Supplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 28407045
TI - Novel pathogenesis: regulation of apoptosis by Apelin/APJ system.
AB - Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G
protein-coupled receptors family. Recent evidence strongly suggests that
Apelin/APJ system influences apoptosis in various diseases through different
signal pathways. In this review, we discuss the possible mechanisms by which the
Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase
(PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize
the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion
(I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute
renal injury, skeletal homeostasis, and gastrointestinal diseases. Apelin/APJ
system decreases myocardial infarction size and alleviates myocardial I/R injury
by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves
pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts
neuroprotective effect by blocking apoptosis and participates in the recovery of
retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also
shows anti-apoptotic effect against acute renal injury and plays a role in
regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system
plays a potential physiological role in gastrointestinal cytoprotection by
regulating apoptosis. We hope that a better understanding of the Apelin/APJ
system will help to discover new disease pathogenesis and find possible
therapeutic targets of the Apelin/APJ system essential for various diseases.
PMID- 28407044
TI - Health Insurance Type and Control of Hypertension Among US Women Living With and
Without HIV Infection in the Women's Interagency HIV Study.
AB - BACKGROUND: Health care access is an important determinant of health. We assessed
the effect of health insurance status and type on blood pressure control among US
women living with (WLWH) and without HIV. METHODS: We used longitudinal cohort
data from the Women's Interagency HIV Study (WIHS). WIHS participants were
included at their first study visit since 2001 with incident uncontrolled blood
pressure (BP) (i.e., BP >=140/90 and at which BP at the prior visit was
controlled (i.e., <135/85). We assessed time to regained BP control using inverse
Kaplan-Meier curves and Cox proportional hazard models. Confounding and selection
bias were accounted for using inverse probability-of-exposure-and-censoring
weights. RESULTS: Most of the 1,130 WLWH and 422 HIV-uninfected WIHS participants
who had an elevated systolic or diastolic measurement were insured via Medicaid,
were African-American, and had a yearly income <=$12,000. Among participants
living with HIV, comparing the uninsured to those with Medicaid yielded an 18
month BP control risk difference of 0.16 (95% CI: 0.10, 0.23). This translates
into a number-needed-to-treat (or insure) of 6; to reduce the caseload of WLWH
with uncontrolled BP by one case, five individuals without insurance would need
to be insured via Medicaid. Blood pressure control was similar among WLWH with
private insurance and Medicaid. There were no differences observed by health
insurance status on 18-month risk of BP control among the HIV-uninfected
participants. CONCLUSIONS: These results underscore the importance of health
insurance for hypertension control-especially for people living with HIV.
PMID- 28407046
TI - RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced
pulmonary hypertension.
AB - Aims: Extracellular matrix (ECM) proteins accumulation contributes to the
progression of pulmonary arterial hypertension (PAH), a rare and fatal
cardiovascular condition defined by high pulmonary arterial pressure, whether
primary, idiopathic, or secondary to other causes. The receptor for advanced
glycation end products (RAGE) is constitutively expressed in the lungs and plays
an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE
mediates ECM deposition/formation in pulmonary arteries and its roles in PAH
progression remain unclear. Methods and results: Expression of RAGE and its
activating ligands, S100/calgranulins and high mobility group box 1 (HMGB1), were
increased in both human and mouse pulmonary arterial smooth muscle cells (PASMCs)
under hypoxic conditions and were also strikingly upregulated in pulmonary
arteries in hypoxia plus SU5416 (HySu)-induced PAH in mice. RAGE deletion
alleviated pulmonary arterial pressure and restrained extracellular matrix
accumulation in pulmonary arteries in HySu-induced PAH murine model. Moreover,
blocking RAGE activity with a neutralizing antibody in human PASMCs, or RAGE
deficiency in mouse PASMCs exposed to hypoxia, suppressed the expression of
fibrotic proteins by reducing TGF-beta1 expression. RAGE reconstitution in
deficient mouse PASMCs restored hypoxia-stimulated TGF-beta1 production via
ERK1/2 and p38 MAPK pathway activation and subsequently increased ECM protein
expression. Interestingly, HMGB1 acting on RAGE, not toll-like receptor 4 (TLR4),
induced ECM deposition in PASMCs. Finally, in both idiopathic PAH patients and
HySu-induced PAH mice, soluble RAGE (sRAGE) levels in serum were significantly
elevated compared to those in controls. Conclusions: Activation of RAGE
facilitates the development of hypoxia-induced pulmonary hypertension by increase
of ECM deposition in pulmonary arteries. Our results indicate that sRAGE may be a
potential biomarker for PAH diagnosis and disease severity, and that RAGE may be
a promising target for PAH treatment.
PMID- 28407047
TI - Identification of Candidate Odorant-Binding Protein and Chemosensory Protein
Genes in Cyrtorhinus lividipennis (Hemiptera: Miridae), a Key Predator of the
Rice Planthoppers in Asia.
AB - Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae) is an important predatory
natural enemy of planthopper and leafhopper eggs in Asian rice paddy fields.
Cyrtorhinus lividipennis is known to rely largely on herbivore-induced plant
volatiles to identify eggs embedded in rice stem tissues for feeding and on
pheromones for mating. However, exactly how C. lividipennis decode these chemical
information is unclear. In most insects, the odorant-binding proteins (OBPs) and
the chemosensory proteins (CSPs) are essential for seeking out food resources and
mates. In this study, we identified 10 OBP and 5 CSP genes in C. lividipennis and
investigated their expression patterns in various tissues of adult males and
females by quantitative real-time PCR (qRT-PCR). Six OBP genes (ClivOBP1, 2, 4,
6, 9, and 10) were mainly expressed in the male antennae, whereas three genes
(ClivOBP3, ClivOBP7, and ClivOBP8) had high expression in the female antennae.
ClivCSP1 was predominantly expressed in the male antennae. These findings suggest
that most ClivOBPs and ClivCSPs are likely involved in food-searching behavior.
The recognition of the pheromone molecules provides the basis for further
functional studies on the chemoreception system of C. lividipennis.
PMID- 28407048
TI - Response to Tautological Nature of Guyton's Theory of Blood Pressure Control.
PMID- 28407049
TI - Corrigendum.
PMID- 28407050
TI - Infarct size, left ventricular function, and prognosis in women compared to men
after primary percutaneous coronary intervention in ST-segment elevation
myocardial infarction: results from an individual patient-level pooled analysis
of 10 randomized trials.
AB - Aim: Studies have reported less favourable outcomes in women compared with men
after primary percutaneous coronary intervention (PCI) in ST-segment elevation
myocardial infarction (STEMI). Whether sex-specific differences in the magnitude
or prognostic impact of infarct size or post-infarction cardiac function explain
this finding is unknown. Methods and results: We pooled patient-level data from
10 randomized primary PCI trials in which infarct size was measured within 1
month (median 4 days) by either cardiac magnetic resonance imaging or technetium
99m sestamibi single-photon emission computed tomography. We assessed the
association between sex, infarct size, and left ventricular ejection fraction
(LVEF) and the composite rate of death or heart failure (HF) hospitalization
within 1 year. Of 2632 patients with STEMI undergoing primary PCI, 587 (22.3%)
were women. Women were older than men and had a longer delay between symptom
onset and reperfusion. Infarct size did not significantly differ between women
and men, and women had higher LVEF. Nonetheless, women had a higher 1-year rate
of death or HF hospitalization compared to men, and while infarct size was a
strong independent predictor of 1-year death or HF hospitalization (P < 0.0001),
no interaction was present between sex and infarct size or LVEF on the risk of
death or HF hospitalization. Conclusions: In this large-scale, individual patient
level pooled analysis of patients with STEMI undergoing primary PCI, women had a
higher 1-year rate of death or HF hospitalization compared to men, a finding not
explained by sex-specific differences in the magnitude or prognostic impact of
infarct size or by differences in post-infarction cardiac function.
PMID- 28407052
TI - Urine albumin excretion and the risk of incident atrial fibrillation: predictive
or aetiological relevance?
PMID- 28407051
TI - IGF1R Expression in Ovarian Granulosa Cells Is Essential for Steroidogenesis,
Follicle Survival, and Fertility in Female Mice.
AB - Folliculogenesis is a lengthy process that requires the proliferation and
differentiation of granulosa cells (GCs) for preovulatory follicle formation. The
most crucial endocrine factor involved in this process is follicle-stimulating
hormone (FSH). Interestingly, previous in vitro studies indicated that FSH does
not stimulate GC proliferation in the absence of the insulinlike growth factor 1
receptor (IGF1R). To determine the role of the IGF1R in vivo, female mice with a
conditional knockdown of the IGF1R in the GCs were produced and had undetectable
levels of IGF1R mRNA and protein in the GCs. These animals were sterile, and
their ovaries were smaller than those of control animals and contained no antral
follicles even after gonadotropin stimulation. The lack of antral follicles
correlated with a 90% decrease in serum estradiol levels. In addition, under a
superovulation protocol no oocytes were found in the oviducts of these animals.
Accordingly, the GCs of the mutant females expressed significantly lower levels
of preovulatory markers including aromatase, luteinizing hormone receptor, and
inhibin alpha. In contrast, no alterations in FSH receptor expression were
observed in GCs lacking IGF1R. Immunohistochemistry studies demonstrated that
ovaries lacking IGF1R had higher levels of apoptosis in follicles from the
primary to the large secondary stages. Finally, molecular studies determined that
protein kinase B activation was significantly impaired in mutant females when
compared with controls. These in vivo findings demonstrate that IGF1R has a
crucial role in GC function and, consequently, in female fertility.
PMID- 28407053
TI - EuroEcho-Imaging 2016: highlights.
AB - The annual meeting of the European Association of Cardiovascular Imaging,
EuroEcho-Imaging, was held in Leipzig, Germany, in December 2016. In the present
paper, we present a summary of the 'Highlights' session.
PMID- 28407054
TI - Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community
Acquired Pneumonia.
AB - Background: Recent trials suggest procalcitonin-based guidelines can reduce
antibiotic use for respiratory infections. However, the accuracy of procalcitonin
to discriminate between viral and bacterial pneumonia requires further
dissection. Methods: We evaluated the association between serum procalcitonin
concentration at hospital admission with pathogens detected in a multicenter
prospective surveillance study of adults hospitalized with community-acquired
pneumonia. Systematic pathogen testing included cultures, serology, urine antigen
tests, and molecular detection. Accuracy of procalcitonin to discriminate between
viral and bacterial pathogens was calculated. Results: Among 1735 patients,
pathogens were identified in 645 (37%), including 169 (10%) with typical
bacteria, 67 (4%) with atypical bacteria, and 409 (24%) with viruses only. Median
procalcitonin concentration was lower with viral pathogens (0.09 ng/mL;
interquartile range [IQR], <0.05-0.54 ng/mL) than atypical bacteria (0.20 ng/mL;
IQR, <0.05-0.87 ng/mL; P = .05), and typical bacteria (2.5 ng/mL; IQR, 0.29-12.2
ng/mL; P < .01). Procalcitonin discriminated bacterial pathogens, including
typical and atypical bacteria, from viral pathogens with an area under the
receiver operating characteristic (ROC) curve of 0.73 (95% confidence interval
[CI], .69-.77). A procalcitonin threshold of 0.1 ng/mL resulted in 80.9% (95% CI,
75.3%-85.7%) sensitivity and 51.6% (95% CI, 46.6%-56.5%) specificity for
identification of any bacterial pathogen. Procalcitonin discriminated between
typical bacteria and the combined group of viruses and atypical bacteria with an
area under the ROC curve of 0.79 (95% CI, .75-.82). Conclusions: No procalcitonin
threshold perfectly discriminated between viral and bacterial pathogens, but
higher procalcitonin strongly correlated with increased probability of bacterial
pathogens, particularly typical bacteria.
PMID- 28407055
TI - Inequalities in obesity in Portugal: regional and gender differences.
AB - Background: Obesity levels vary considerably according to geographical region and
socio-economic status. We evaluated the prevalence of obesity by education and
occupational position across seven Portuguese regions. Relative and absolute
inequalities in obesity were also assessed. Methods: Data was drawn from the
Portuguese Health Survey 2005/6 (26 674 adults, 46.6% women). Education was
categorized as <=4, 5-11 and >=12 complete years of education. Occupational
position was grouped as upper white collar, lower white collar and blue collar.
The Relative Index of Inequality (RII) and the Slope Index of Inequality (SII)
were used to quantify relative and absolute inequalities in obesity,
respectively. Results: In women, prevalence of obesity ranged between 10.0%
(Algarve) and 20.3% (Azores); in men, it ranged between 13.3% (Algarve) and 16.4%
(Lisbon). In women, the educational RII (95% confidence interval) ranged between
2.4 (1.1 to 5.1) in the Centre and 6.6 (3.0 to 14.2) in Alentejo, and the SII
(95% CI) between 9.7 (-1.3 to 20.7) and 33.0 (26.0 to 40.0), respectively. In
men, the RII ranged between 0.8 (0.4 to 1.5) in Madeira and 1.9 (1.0 to 4.5) in
the Centre, and the SII between -8.3 (-19.0 to 2.5) and 9.5 (-0.1 to 19.1),
respectively. Occupational RIIs were similar to those for education, although
somewhat lower. Conclusion: In Portugal, large educational and occupational
inequalities in obesity are observed, but they vary considerably by region and
are larger among women than men.
PMID- 28407056
TI - Atrial fibrillation: a mechanism or just a bystander?
PMID- 28407057
TI - Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral
Cortex Development.
AB - Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an
essential role in neurodevelopment; however, the mechanisms underlying T3 brain
delivery during mice fetal development are not well known. This work has explored
the sources of brain T3 during mice fetal development using biochemical,
anatomical, and molecular approaches. The findings revealed that during late
gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the
developing mouse brain, fetal T3 content is regulated through the conversion of
T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier
prenatal stages. Additionally, D2 activity was found to be essential to mediate
expression of T3-dependent genes in the cerebral cortex, and also necessary to
generate the transient cerebral cortex hyperthyroidism present in mice lacking
the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for
D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB).
Overall, these data signify that T4 deiodinated by D2 may be the only source of
T3 during neocortical development. We therefore propose that D2 activity at the
BCSFB converts the T4 transported across the choroid plexus into T3, thus
supplying the brain with active hormone to maintain TH homeostasis.
PMID- 28407058
TI - Access to healthcare for undocumented migrants: analysis of avoidable hospital
admissions in Sicily from 2003 to 2013.
AB - Background: Access to healthcare services for undocumented migrants is one of the
main public health issues currently being debated among European countries.
Exclusion from primary healthcare services may lead to serious consequences for
migrants' health. We analyzed the risk among undocumented migrants, in comparison
with regular migrants, of being hospitalized for preventable conditions in the
Region of Sicily (Italy). We performed a hospital-based cross-sectional study of
the foreign population hospitalized in the Sicily region between 1 January 2003
and 31 December 2013. The first outcome was the proportion of avoidable
hospitalization (AHs) among regular and irregular migrants. Second outcomes were
the subcategories of AHs for chronic, acute and vaccine preventable diseases. 85
309 hospital admissions were analyzed. In the hospitalized population, in
comparison to regular migrants, undocumented migrants show a higher proportion of
hospitalization for diseases preventable through primary and preventive care
(AOR1.48, 95%CI 1.37-1.59). The proportion of avoidable hospitalizations
associated with the lack of legal status is higher for vaccine preventable
conditions (AOR 2.06, 95%CI 1.66-2.56) than for chronic conditions (AOR 1.47,
95%CI 1.42-1.63) and acute conditions (AOR 1.37; 95%CI 1.23-1.53). Between 2003
and 2013, the proportion of avoidable hospitalizations decreased both in regular
and undocumented migrants but decreased faster for regular than for undocumented
migrants. Undocumented migrants experience higher proportion of hospitalization
for preventable conditions in comparison with regular migrants probably due to a
lack of access to the national healthcare service. Policies and strategies to
involve them in primary healthcare and preventive services should be developed to
tackle this inequality.
PMID- 28407059
TI - Septal artery diastolic flow profile in hypertrophic restrictive cardiomyopathy:
Doppler square root sign!
PMID- 28407061
TI - Lifetime abuse and perceived social support among the elderly: a study from seven
European countries.
AB - Background: Being a victim of abuse during one's life course may affect social
relations in later life. The aims of this study were to: (i) examine the
association between lifetime abuse and perceived social support and (ii) identify
correlates of perceived social support among older persons living in seven
European countries. Methods: A sample of 4467 women and men aged 60-84 years
living in Germany, Greece, Italy, Lithuania, Portugal, Spain and Sweden was
collected through a cross-sectional population-based study. Abuse (psychological,
physical, sexual, financial and injury) was assessed through interviews or
interviews/self-response questionnaire based on the Conflict Tactics Scale-2 and
the UK study on elder abuse. Perceived social support was assessed by the
Multidimensional Scale of Perceived Social Support. Results: Victims of lifetime
abuse perceived poorer social support in later life. Multivariate analyses showed
that high levels of perceived social support were associated with being from
Greece and Lithuania (compared to Germany), being female, not living alone,
consuming alcohol and physical activity. Poorer perceived social support was
associated with being from Portugal, being old, having social benefits as the
main source of income, experiencing financial strain and being exposed to
lifetime psychological abuse and injuries. Conclusions: Our findings showed that
exposure to psychological abuse and injuries across the lifespan were associated
with low levels of perceived social support, emphasizing the importance of
detection and appropriate treatment of victims of abuse during their life course.
Future research should focus on coping strategies buffering the negative effects
of abuse on social relationships.
PMID- 28407062
TI - Voltage gradient mapping and electrophysiologically guided cryoablation in
children with AVNRT.
AB - Aims: Recently, voltage gradient mapping of Koch's triangle to find low-voltage
connections, or 'voltage bridges', corresponding to the anatomic position of the
slow pathway, has been introduced as a method to ablate atrioventricular nodal
reentry tachycardia (AVNRT) in children. Thus, we aimed to assess the
effectiveness of voltage mapping of Koch's triangle, combined with the search for
the slow potential signal in 'low-voltage bridges', to guide cryoablation of
AVNRT in children. Methods and results: From June 2015 to May 2016, 35
consecutive paediatric patients (mean age 12.1 +/- 4.5 years) underwent 3D-guided
cryoablation of AVNRT at our Institution. Fifteen children were enrolled as
control group (mean age 14 +/- 4 years). A voltage gradient mapping of Koch's
triangle was obtained in all patients, showing low-voltage connections in all
children with AVNRT but not in controls. Prior to performing cryoablation, we
looked for the typical 'hump and spike' electrogram, generally considered to be
representative of slow pathway potential within a low-voltage bridge. In all
patients the 'hump and spike' electrogram was found inside bridges of low
voltage. Focal or high-density linear lesions, extended or not, were delivered
guided by low-voltage bridge visualization. Acute success rate was 100%, and no
recurrence was reported at a mean follow-up of 8 +/- 3 months. Conclusions:
Voltage gradient mapping of Koch's triangle, combined with the search for the
slow potential signal in low-voltage bridges, is effective in guiding
cryoablation of AVNRT in paediatric patients, with a complete acute success rate
and no AVNRT recurrences at mid-term follow-up.
PMID- 28407063
TI - Trends in the sexual behaviour of 15-year olds in Scotland: 2002-14.
AB - Background: Early sexual initiation and inadequate contraceptive use can place
adolescents at increased risk of unplanned pregnancy and sexually transmitted
infections. These behaviours are patterned by gender and may be linked to social
inequalities. This paper examines trends in sexual initiation and contraceptive
use by gender and family affluence for Scottish adolescents. Methods: Cross
sectional data from four nationally representative survey cycles (2002, 2004,
2010, 2014) (n = 8895) (mean age = 15.57) were analysed. Logistic regressions
examined the impact of survey year on sexual initiation, condom use and birth
control pill (BCP) use at last sex; as well as any changes over time in
association between family affluence and the three sexual behaviours. Analyses
were stratified by gender. Results: Between 2002 and 2014, adolescent males and
females became less likely to report having had sex. Low family affluence females
were more likely to have had sex than high family affluence females, and this
relationship did not change over time. Condom use at last sex was reported less
by males since 2002, and by females since 2006. Low family affluence males and
females were less likely to use condoms than high family affluence participants,
and these relationships did not change over time. There were no effects of time
or family affluence for BCP use. Conclusion: There has been a reduction in the
proportion of 15-year olds in Scotland who have ever had sex, but also a decrease
in condom use for this group. Economic inequalities persist for sexual initiation
and condom use.
PMID- 28407060
TI - Role of Osteoblast Gi Signaling in Age-Related Bone Loss in Female Mice.
AB - Age-related bone loss is an important risk factor for fractures in the elderly;
it results from an imbalance in bone remodeling mainly due to decreased bone
formation. We have previously demonstrated that endogenous G protein-coupled
receptor (GPCR)-driven Gi signaling in osteoblasts (Obs) restrains bone formation
in mice during growth. Here, we launched a longitudinal study to test the
hypothesis that Gi signaling in Obs restrains bone formation in aging mice,
thereby promoting bone loss. Our approach was to block Gi signaling in maturing
Obs by the induced expression of the catalytic subunit of pertussis toxin (PTX)
after the achievement of peak bone mass. In contrast to the progressive
cancellous bone loss seen in aging sex-matched littermate control mice, aging
female Col1(2.3)+/PTX+ mice showed an age-related increase in bone volume.
Increased bone volume was associated with increased bone formation at both
trabecular and endocortical surfaces as well as increased bending strength of the
femoral middiaphyses. In contrast, male Col1(2.3)+/PTX+ mice were not protected
from age-related bone loss. Our results indicate that Gi signaling markedly
restrains bone formation at cancellous and endosteal bone surfaces in female mice
during aging. Blockade of the relevant Gi-coupled GPCRs represents an approach
for the development of osteoporosis therapies-at least in the long bones of aging
women.
PMID- 28407064
TI - The Influence of Eye Closure on Somatosensory Discrimination: A Trade-off Between
Simple Perception and Discrimination.
AB - We often close our eyes to improve perception. Recent results have shown a
decrease of perception thresholds accompanied by an increase in somatosensory
activity after eye closure. However, does somatosensory spatial discrimination
also benefit from eye closure? We previously showed that spatial discrimination
is accompanied by a reduction of somatosensory activity. Using
magnetoencephalography, we analyzed the magnitude of primary somatosensory
(somatosensory P50m) and primary auditory activity (auditory P50m) during a one
back discrimination task in 21 healthy volunteers. In complete darkness,
participants were requested to pay attention to either the somatosensory or
auditory stimulation and asked to open or close their eyes every 6.5 min.
Somatosensory P50m was reduced during a task requiring the distinguishing of
stimulus location changes at the distal phalanges of different fingers. The
somatosensory P50m was further reduced and detection performance was higher
during eyes open. A similar reduction was found for the auditory P50m during a
task requiring the distinguishing of changing tones. The function of eye closure
is more than controlling visual input. It might be advantageous for perception
because it is an effective way to reduce interference from other modalities, but
disadvantageous for spatial discrimination because it requires at least one top
down processing stage.
PMID- 28407066
TI - Emergence and molecular characterization of Haemophilus influenzae harbouring
mef(A)-authors' response.
PMID- 28407065
TI - Reduced and declining physical function in prevalent dialysis patients
identifying the vulnerable.
PMID- 28407067
TI - Evaluation of a Second-Sign Process for Antimicrobial Prior Authorization.
AB - Background: A second-sign prospective restriction of select broad-spectrum
antimicrobials was fully implemented in January 2015 as a pediatric antimicrobial
stewardship program (ASP) initiative to help ensure the most appropriate empiric
use of ceftaroline, cefepime, fidaxomicin, linezolid, and vancomycin
(intravenous). The objective of this evaluation is to assess the effectiveness of
a forced second-sign process in the electronic medical record as a pediatric ASP
strategy. We anticipated that the second-sign process for antibiotics would
increase the appropriateness of empiric antibiotic use, as defined by preapproved
criteria, clinical pathways, national guidelines, and pediatric-specific
infectious diseases reference texts, while not causing significant delay in the
initial administration of antibiotic therapy. Methods: This was a retrospective
before and after intervention chart review conducted from July 2014 to June 2015.
The study was conducted at a 187-bed, freestanding teaching children's hospital
that included the following: level-1 pediatric trauma center, 18-bed pediatric
intensive care unit, and 32-bed neonatal intensive care unit. Results: A total of
1178 orders were identified, and 389 met inclusion criteria. The vast majority of
second-sign orders were for vancomycin (92%), 61% were written for males, and the
median age was 6 years old. Appropriateness of second-sign restricted antibiotic
use significantly increased after second-sign implementation (84.5% to 92.9%, P =
.01). The secondary outcome of time from initial order entry to medication
administration was not different between the before and after groups (median
time, 184.5 [interquartile range, 110.25-280.75] vs 174 [interquartile range, 104
228] minutes; P = .342). Conclusions: The use of a second-sign approval process
for antimicrobial restriction can lead to increased appropriateness of antibiotic
use at a pediatric hospital, without causing a delay in administration.
PMID- 28407068
TI - A successful model for longitudinal community-engaged health research: the 2040
Partners for Health Student Program.
AB - Introduction: Community-based participatory research [CBPR] is an emerging
approach to collaborative research aimed at creating locally effective and
sustainable interventions. The 2040 Partners for Health student program was
developed as a unique model of longitudinal CBPR. Analysis of this program and
its components illuminates both the challenges and the opportunities inherent in
community engagement. Methods: The program rests on a foundation of a community
based, non-profit organization and a supportive academic university centre. Inter
professional health students and community members of underserved populations
work together on different health projects by employing an adapted CBPR
methodology. Three successful examples of sustainable CBPR projects are briefly
described. Results: The three projects are presented as primary outcomes
resulting from this model. Benefits and challenges of the model as an approach to
community-engaged research are discussed as well as secondary benefits of student
participation. Conclusion: The 2040 Partners for Health student program
represents a successful model of CBPR, illuminating common challenges and
reiterating the profound value of community-engaged research.
PMID- 28407069
TI - Managing transient ischaemic attacks in Australia: a qualitative study.
AB - Background: Stroke risk after transient ischaemic attack (TIA) is highest in the
first few days. It is greatly reduced by commencing commonly used medications.
Current Australian guidelines recommend that all TIAs be managed urgently by
secondary-care specialists (mandatory for high-risk TIAs). The majority of TIAs
present to general practice which creates a dilemma when specialist care is not
readily accessible. There is a lack of evidence relating to the determinants of
general practitioners' (GPs) actions in this situation. Objective: To explore GP
management of TIA presentations. Methods: A qualitative study using semi
structured interviews of a maximum variation sample of senior and trainee GPs
from New South Wales, Australia. Data collection and thematic analysis were
concurrent and iterative, employing constant comparison, co-coding, participant
transcript review, reflexivity and continued until thematic saturation was
achieved. Results: Management of TIA was heterogeneous and depended upon the GP's
engagement with the individual case. The level of engagement was predicated on
the GP's predisposition toward managing transient neurological presentations
generally, the clinical phenotype of the presentation and logistical or health
system factors. Management was categorised as triage, guided collaboration,
consultative collaboration and independent management. Collaboration with
secondary care increased the GP's capability to diagnose and manage future TIAs.
Conclusion: Heterogeneity of TIA management equates with variation from guideline
recommendations. However, Australian guidelines may not be practicable due to
variability in access to secondary-care specialists. Future models of care should
consider systems approaches such as telemedicine to promote collaboration and
assist GPs to comply with guidelines.
PMID- 28407070
TI - Effective HIV Prevention Interventions and the Need for Rapid Mobilization to
Address HIV Outbreaks Among At-Risk Populations.
PMID- 28407072
TI - Beneficial Nonspecific Effects of Oral Polio Vaccine (OPV): Implications for the
Cessation of OPV?
PMID- 28407071
TI - Decline in RNA integrity of dry-stored soybean seeds correlates with loss of
germination potential.
AB - This study investigates the relationship between germination ability and damage
to RNA in soybean seeds (cv 'Williams 82') stored dry at 5 degrees C for 1-27
years. Total germination of 14 age cohorts harvested between 2015 and 1989 ranged
from 100% to 3%. Germination decline followed classic seed viability kinetics,
with symptomatic seed aging beginning after 17 years of storage. RNA integrity
was assessed in dry seeds by electrophoresis of total RNA, followed by
calculation of the RNA integrity number (RIN, Agilent Bioanalyzer software),
which evaluates RNA fragment size distributions. Analysis of RNA extracted from
cotyledons, embryonic axes, plumules, and seed coats across the range of age
cohorts showed consistent RNA degradation: older seeds had over-representation of
small RNAs compared with younger seeds, which had nearly a 2:1 ratio of 25S and
18S rRNAs. RIN values for cotyledons and embryonic axes from the same seed were
correlated. Decline in RIN tracked reduced germination, with a pronounced
decrease in RIN after 17 years of storage. This led to a high correlation between
the mean RIN of cotyledon RNA and the total germination percentage (R2=0.91,
P<0.0001). Despite this relationship, germinable and non-germinable seeds within
cohorts could not be distinguished unless the RIN was <3.5, indicating
substantial deterioration. Our work demonstrates that seed RNA incurs damage over
time, observable in fragment size distributions. Under the experimental
conditions used here, RIN appears to be a promising surrogate for germination
tests used to monitor viability of stored seeds.
PMID- 28407073
TI - Uptake, sequestration and tolerance of cadmium at cellular levels in the
hyperaccumulator plant species Sedum alfredii.
AB - Sedum alfredii is one of a few plant species known to hyperaccumulate cadmium
(Cd). Uptake, localization, and tolerance of Cd at cellular levels in shoots were
compared in hyperaccumulating (HE) and non-hyperaccumulating (NHE) ecotypes of
Sedum alfredii. X-ray fluorescence images of Cd in stems and leaves showed only a
slight Cd signal restricted within vascular bundles in the NHEs, while enhanced
localization of Cd, with significant tissue- and age-dependent variations, was
detected in HEs. In contrast to the vascular-enriched Cd in young stems,
parenchyma cells in leaf mesophyll, stem pith and cortex tissues served as
terminal storage sites for Cd sequestration in HEs. Kinetics of Cd transport into
individual leaf protoplasts of the two ecotypes showed little difference in Cd
accumulation. However, far more efficient storage of Cd in vacuoles was apparent
in HEs. Subsequent analysis of cell viability and hydrogen peroxide levels
suggested that HE protoplasts exhibited higher resistance to Cd than those of NHE
protoplasts. These results suggest that efficient sequestration into vacuoles, as
opposed to rapid transport into parenchyma cells, is a pivotal process in Cd
accumulation and homeostasis in shoots of HE S. alfredii. This is in addition to
its efficient root-to-shoot translocation of Cd.
PMID- 28407074
TI - Comment on: Emergence and molecular characterization of Haemophilus influenzae
harbouring mef(A).
PMID- 28407075
TI - Once-daily atazanavir/cobicistat and darunavir/cobicistat exposure over 72 h post
dose in plasma, urine and saliva: contribution to drug pharmacokinetic knowledge.
AB - Background: We investigated the pharmacokinetics (PK) of atazanavir/cobicistat
and darunavir/cobicistat once daily over 72 h following drug intake cessation in
plasma, saliva and urine. Methods: Healthy volunteers received a fixed-dose
combination of 300/150 mg of atazanavir/cobicistat once daily for 10 days,
followed by a 10 day washout period and then a fixed-dose combination of 800/150
mg of darunavir/cobicistat once daily for 10 days. Full PK profiles were assessed
for each phase for 72 h following day 10 and parameters determined to the last
measurable concentration in plasma, saliva and urine by non-compartmental
methods. Results: Sixteen subjects completed the study. Geometric mean (GM)
terminal elimination half-life values to 72 h of atazanavir and darunavir were
6.77 and 6.35 h, respectively. All subjects had atazanavir concentrations above
the suggested minimum effective concentration of 150 ng/mL 24 h post-dose and
14/16 subjects had concentrations higher than this target at 30 h post-dose (GM
of 759 and 407 ng/mL, respectively). Thirteen out of 16 subjects had darunavir
concentrations higher than the target of 550 ng/mL at 24 h post-dose and 5/16
subjects had concentrations higher than the target at 30 h post-dose (GM of 1033
and 382 ng/mL, respectively). Cobicistat half-life to 72 h was 4.21 h with
atazanavir and 3.62 h with darunavir. GM values 24 h after the observed dose ( C
24 ) for atazanavir and darunavir were 141 and 43 ng/mL, respectively, in saliva
and 24857 and 11878 ng/mL, respectively, in urine. Concentration decay in
saliva/urine mirrored plasma concentrations for both drugs. Conclusions:
Different concentration decay patterns were seen for atazanavir and darunavir,
which may be partially explained by cobicistat half-life (longer with atazanavir
than darunavir). For the first time, we also measured drug PK forgiveness in
saliva and urine, which represent easier markers of adherence.
PMID- 28407076
TI - Differential gene expression and transport functionality in the bundle sheath
versus mesophyll - a potential role in leaf mineral homeostasis.
AB - Under fluctuating ambient conditions, the ability of plants to maintain
hydromineral homeostasis requires the tight control of long distance transport.
This includes the control of radial transport within leaves, from veins to
mesophyll. The bundle sheath is a structure that tightly wraps around leaf
vasculature. It has been suggested to act as a selective barrier in the context
of radial transport. This suggestion is based on recent physiological transport
assays of bundle sheath cells (BSCs), as well as the anatomy of these cells.We
hypothesized that the unique transport functionality of BSCs is apparent in their
transcriptome. To test this, we compared the transcriptomes of individually hand
picked protoplasts of GFP-labeled BSCs and non-labeled mesophyll cells (MCs) from
the leaves of Arabidopsis thaliana. Of the 90 genes differentially expressed
between BSCs and MCs, 45% are membrane related and 20% transport related, a
prominent example being the proton pump AHA2. Electrophysiological assays showed
that the major AKT2-like membrane K+ conductances of BSCs and MCs had different
voltage dependency ranges. Taken together, these differences may cause
simultaneous but oppositely directed transmembrane K+ fluxes in BSCs and MCs, in
otherwise similar conditions.
PMID- 28407077
TI - Chemosensory Responses to the Repellent Nepeta Essential Oil and Its Major
Component Nepetalactone by Aedes aegypti (Diptera: Culicidae), a Vector of Zika
Virus.
AB - Nepeta essential oil (Neo; catnip) and its major component, nepetalactone, have
long been known to repel insects including mosquitoes. However, the neural
mechanisms through which these repellents are detected by mosquitoes, including
the yellow fever mosquito Aedes aegypti (L.), an important vector of Zika virus,
were poorly understood. Here we show that Neo volatiles activate olfactory
receptor neurons within the basiconic sensilla on the maxillary palps of female
Ae. aegypti. A gustatory receptor neuron sensitive to the feeding deterrent
quinine and housed within sensilla on the labella of females was activated by
both Neo and nepetalactone. Activity of a second gustatory receptor neuron
sensitive to the feeding stimulant sucrose was suppressed by both repellents. Our
results provide neural pathways for the reported spatial repellency and feeding
deterrence of these repellents. A better understanding of the neural input
through which female mosquitoes make decisions to feed will facilitate design of
new repellents and management strategies involving their use.
PMID- 28407079
TI - Incidence rate for larynx cancer in Japanese in Japan and in the United States
from the Cancer Incidence in Five Continents.
PMID- 28407078
TI - Inulin with different degrees of polymerization modulates composition of
intestinal microbiota in mice.
AB - The study aimed to analyze the global influences of dietary inulin with different
degrees of polymerization (DP) on intestinal microbial communities. Six-week-old
male C57BL/6J mice were treated with fructo-oligosaccharides and inulin for 6
weeks. Fecal samples were obtained at time point 0 and 6th week. 16S rRNA
sequence analysis was used to measure intestinal microbiota performed on the
Illumina MiSeq platform. Influences of dietary inulin on intestinal microbiota
were more complex effects than bifidogenic effects, relative abundance of
butyrate-producing bacteria increased after interventions. Akkermansia
muciniphila, belonging to mucin-degrading species, became a dominant species in
Verrucomicrobia phylum after treatment with fructo-oligosaccharides and inulin.
Modulation effects of intestinal microbiota were positively correlated with DP.
Lower DP interventions exhibited better effects than higher DP treatment on
stimulation of probiotics. We hypothesized that Akkermansia muciniphila played an
important role on maintaining balance between mucin and short chain fatty acids.
PMID- 28407081
TI - Isolation of Early-Responsive MicroRNA From Diuraphis noxia (Hemiptera:
Aphididae)-Resistant Wheat.
AB - The Russian wheat aphid (Diuraphis noxia Kurdjumov) is an economically important
pest of small grains in many countries. The past decades have seen the deployment
of resistance-carrying wheat (Triticum aestivum L.) cultivars to control D.
noxia. However, the emergence of resistance-breaking biotypes is negating this
strategy. The role that noncoding RNA (ncRNA) molecules play in the wheat-D.
noxia interaction has not been studied to date. This study aimed to isolate
differentially regulated microRNA from a resistant and susceptible near-isogenic
wheat line after aphid infestation. Twenty-seven identified miRNA were mostly
related to stress-linked miRNA, and their predicted targets were linked with
known D. noxia-feeding regulated proteins. These included transcription factors,
signaling proteins, carbohydrate metabolism, and disease resistance pathways.
Gene expression of three putative miRNAs and a predicted nucleotide-binding
leucine-rich repeat gene with an identified miRNA target site in the NB-ARC
domain displayed differential regulation between the resistant and susceptible
plants. This study marks the initial investigation into understanding the role of
ncRNA in a D. noxia-resistant wheat line after infestation and reports a
correlation between a miRNA and its putative target for this interaction.
PMID- 28407080
TI - Genome-wide changes in microRNA expression during short and prolonged heat stress
and recovery in contrasting rice cultivars.
AB - MicroRNAs (miRNAs) are known to regulate expression of genes under stress. We
report here the deep sequencing of small RNAs expressed during control, short and
prolonged heat stress and recovery. Genome-wide identification of miRNAs in
tolerant (Nagina 22) and susceptible (Vandana) rice cultivars was performed in 16
samples representing root and shoot of 13-day-old seedlings. The expression
profile of miRNAs was analysed in 36 pairwise combinations to identify the
genotype-, treatment- and tissue-dependent expression of miRNAs. Small-RNA
sequencing of 16 libraries yielded ~271 million high-quality raw sequences; 162
miRNA families were identified. The highly expressed miRNAs in rice tissues were
miR166, miR168, miR1425, miR529, mR162, miR1876, and miR1862. Expression of osa
miR1436, osa-miR5076, osa-miR5161, and osa-miR6253 was observed only in stressed
tissue of both genotypes indicating their general role in heat stress response.
Expression of osa-miR1439, osa-miR1848, osa-miR2096, osa-miR2106, osa-miR2875,
osa-miR3981, osa-miR5079, osa-miR5151, osa-miR5484, osa-miR5792, and osa-miR5812
was observed only in Nagina 22 during high temperature, suggesting a specific
role of these miRNAs in heat stress tolerance. This study provides details of the
repertoire of miRNAs expressed in root and shoot of heat susceptible and tolerant
rice genotypes under heat stress and recovery.
PMID- 28407082
TI - Genes and Group Membership Predict Gidgee Skink (Egernia stokesii) Reproductive
Pairs.
AB - Due to their role in mate choice, disease resistance and kin recognition, genes
of the major histocompatibility complex (MHC) are good candidates for
investigating genetic-based mate choice. MHC-based mate choice is context
dependent and influenced by many factors including social structure. Social
structure diversity makes the Egernia group of lizards suitable for comparative
studies of MHC-based mate choice. We investigated mate choice in the gidgee skink
(Egernia stokesii), a lizard that exhibits high levels of social group and
spatial stability. Group membership was incorporated into tests of the good genes
as heterozygosity and compatible genes hypotheses for adaptive (MHC) and neutral
(microsatellite) genetic diversity (n = 47 individuals genotyped). Females were
more likely to pair with a male with higher MHC diversity and with whom they had
a lower degree of microsatellite relatedness. Males were more likely to pair with
a female with higher microsatellite heterozygosity and with whom they shared a
lower proportion of MHC alleles. Lizards were more likely to mate with an
individual from within, rather than outside, their social group, which confirmed
earlier findings for this species and indicated mate choice had already largely
occurred prior to either social group formation or acceptance of an individual
into an existing group. Thus, a combination of genes and group membership, rather
than group membership alone, predicted mate choice in this species. This work
will contribute to an enhanced understanding of squamate group formation and a
deeper understanding of the evolution of sociality within all vertebrates.
PMID- 28407083
TI - Distrusting community health workers with confidential health information: a
convergent mixed-methods study in Swaziland.
AB - Background: Patients are unlikely to share the personal information that is
critical for effective healthcare, if they do not trust that this information
will remain confidential. Trust in confidentiality may be particularly low in
interactions with community health workers (CHW) because CHW deliver healthcare
outside the clinic setting. This study aims to determine the proportion of
Swaziland's population that does not trust the national CHW cadre with
confidential medical information, and to identify reasons for distrust. Methods:
Using two-stage cluster random sampling, we carried out a household survey
covering 2000 households across 100 census enumeration areas in two of
Swaziland's four regions. To confirm and explain the quantitative survey results,
we used qualitative data from 19 semi-structured focus group discussions in the
same population. Results: 49% of household survey participants stated that they
distrust the national CHW cadre with confidential health information. Having ever
been visited by a CHW was positively associated with trust (aOR: 2.11; P <
0.001), while higher levels of schooling of the respondent were negatively
associated (aOR for more than secondary schooling versus no schooling: 0.21; P <
0.001). The following three primary reasons for distrusting CHW with confidential
health information emerged in the qualitative analyses: (1) CHW are members of
the same community as their clients and may thus share information with people
who know the client, (2) CHW are mostly women and several focus group
participants assumed that women are more likely than men to share information
with other community members, and (3) CHW are not sufficiently trained in
confidentiality issues. Conclusion: Our findings suggest that confidentiality
concerns could be a significant obstacle to the successful rollout of CHW
services for stigmatized conditions in Swaziland. Increasing coverage of the CHW
program, raising the population's confidence in CHWs' training, assigning CHW to
work in communities other than the ones in which they live, changing the CHW
gender composition, and addressing gender biases may all increase trust with
regards to confidentiality.
PMID- 28407085
TI - Tautological Nature of Guyton's Theory of Blood Pressure Control.
PMID- 28407084
TI - Comparative analysis of de novo assemblers for variation discovery in personal
genomes.
AB - Current variant discovery approaches often rely on an initial read mapping to the
reference sequence. Their effectiveness is limited by the presence of gaps,
potential misassemblies, regions of duplicates with a high-sequence similarity
and regions of high-sequence divergence in the reference. Also, mapping-based
approaches are less sensitive to large INDELs and complex variations and provide
little phase information in personal genomes. A few de novo assemblers have been
developed to identify variants through direct variant calling from the assembly
graph, micro-assembly and whole-genome assembly, but mainly for whole-genome
sequencing (WGS) data. We developed SGVar, a de novo assembly workflow for
haplotype-based variant discovery from whole-exome sequencing (WES) data. Using
simulated human exome data, we compared SGVar with five variation-aware de novo
assemblers and with BWA-MEM together with three haplotype- or local de novo
assembly-based callers. SGVar outperforms the other assemblers in sensitivity and
tolerance of sequencing errors. We recapitulated the findings on whole-genome and
exome data from a Utah residents with Northern and Western European ancestry
(CEU) trio, showing that SGVar had high sensitivity both in the highly divergent
human leukocyte antigen (HLA) region and in non-HLA regions of chromosome 6. In
particular, SGVar is robust to sequencing error, k-mer selection, divergence
level and coverage depth. Unlike mapping-based approaches, SGVar is capable of
resolving long-range phase and identifying large INDELs from WES, more
prominently from WGS. We conclude that SGVar represents an ideal platform for WES
based variant discovery in highly divergent regions and across the whole genome.
PMID- 28407086
TI - Toward solar biodiesel production from CO2 using engineered cyanobacteria.
AB - Metabolic engineering of cyanobacteria has received attention as a sustainable
strategy to convert carbon dioxide to various biochemicals including fatty acid
derived biodiesel. Recently, Synechococcus elongatus PCC 7942, a model
cyanobacterium, has been engineered to convert CO2 to fatty acid ethyl esters
(FAEEs) as biodiesel. Modular pathway has been constructed for FAEE production.
Several metabolic engineering strategies were discussed to improve the production
levels of FAEEs, including host engineering by improving CO2 fixation rate and
photosynthetic efficiency. In addition, protein engineering of key enzyme in S.
elongatus PCC 7942 was implemented to address issues on FAEE secretions toward
sustainable FAEE production from CO2. Finally, advanced metabolic engineering
will promote developing biosolar cell factories to convert CO2 to feasible amount
of FAEEs toward solar biodiesel.
PMID- 28407087
TI - RP-HPLC Separation of Isomeric Withanolides: Method Development, Validation and
Application to In situ Rat Permeability Determination.
AB - Withanolides are the group of active chemical constituents of Withania somnifera
(L.) Dunal. Withaferin A, withanolide A and withanone presents three of the
biologically most active constituents of this herb. These steroidal lactones are
isomers of each other and thus, pose significant difficulty in their separation.
In present study, a simple, specific and reliable RP-HPLC method has been
developed and validated for their separation and simultaneous quantification.
Separation was carried out on Lichrocart Purospher STAR RP-18e column (250 * 4.5
mm, 5 um) using mobile phase, methanol and 0.01 M ammonium acetate buffer (pH 5)
in the ratio 60:40, v/v. The calibration curves were linear (r2 > 0.99) for all
the three compounds across concentration range of 1.56-50 ug/mL. The lower limit
of quantification for all the analytes was 1.56 ug/mL. The intra-day and inter
day accuracy was between 88.65% and 110.66% and coefficient of variation was
between 0.55 and 10.12. The analytes were stable under different storage
conditions. The developed method was successfully applied to analyze the samples
for simultaneous determination of permeability of the three withanolides in rats
using in situ single-pass intestinal perfusion model. Withanolide A and withanone
were found to be high permeability compounds while withaferin A could not be
detected.
PMID- 28407089
TI - GibbsCluster: unsupervised clustering and alignment of peptide sequences.
AB - Receptor interactions with short linear peptide fragments (ligands) are at the
base of many biological signaling processes. Conserved and information-rich amino
acid patterns, commonly called sequence motifs, shape and regulate these
interactions. Because of the properties of a receptor-ligand system or of the
assay used to interrogate it, experimental data often contain multiple sequence
motifs. GibbsCluster is a powerful tool for unsupervised motif discovery because
it can simultaneously cluster and align peptide data. The GibbsCluster 2.0
presented here is an improved version incorporating insertion and deletions
accounting for variations in motif length in the peptide input. In basic terms,
the program takes as input a set of peptide sequences and clusters them into
meaningful groups. It returns the optimal number of clusters it identified,
together with the sequence alignment and sequence motif characterizing each
cluster. Several parameters are available to customize cluster analysis,
including adjustable penalties for small clusters and overlapping groups and a
trash cluster to remove outliers. As an example application, we used the server
to deconvolute multiple specificities in large-scale peptidome data generated by
mass spectrometry. The server is available at
http://www.cbs.dtu.dk/services/GibbsCluster-2.0.
PMID- 28407088
TI - Borderline resectable pancreatic cancer: conceptual evolution and current
approach to image-based classification.
AB - Background: Diagnostic imaging plays a critical role in the initial diagnosis and
therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the
concept of 'borderline resectable' pancreatic cancer has emerged to describe a
distinct subset of patients existing along the spectrum from resectable to
locally advanced disease for whom a microscopically margin-positive (R1)
resection is considered relatively more likely, primarily due to the relationship
of the primary tumor with surrounding vasculature. Materials and methods: This
review traces the conceptual evolution of borderline resectability from a
radiological perspective, including the debates over the key imaging criteria
that define the thresholds between resectable, borderline resectable, and locally
advanced or metastatic disease. This review also addresses the data supporting
neoadjuvant therapy in this population and discusses current imaging practices
before and during treatment. Results: A growing body of evidence suggests that
the borderline resectable group of patients may particularly benefit from
neoadjuvant therapy to increase the likelihood of an ultimately margin-negative
(R0) resection. Unfortunately, anatomic and imaging criteria to define borderline
resectability are not yet universally agreed upon, with several classification
systems proposed in the literature and considerable variance in institution-by
institution practice. As a result of this lack of consensus, as well as overall
small patient numbers and lack of established clinical trials dedicated to
borderline resectable patients, accurate evidence-based diagnostic categorization
and treatment selection for this subset of patients remains a significant
challenge. Conclusions: Clinicians and radiologists alike should be cognizant of
evolving imaging criteria for borderline resectability given their profound
implications for treatment strategy, follow-up recommendations, and prognosis.
PMID- 28407090
TI - Foods and beverages and colorectal cancer risk: a systematic review and meta
analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous
Update Project.
AB - Objective: As part of the World Cancer Research Fund International Continuous
Update Project, we updated the systematic review and meta-analysis of prospective
studies to quantify the dose-response between foods and beverages intake and
colorectal cancer risk. Data sources: PubMed and several databases up to 31 May
2015. Study selection: Prospective studies reporting adjusted relative risk
estimates for the association of specific food groups and beverages and risk of
colorectal, colon and rectal cancer. Data synthesis: Dose-response meta-analyses
using random effect models to estimate summary relative risks (RRs). Results:
About 400 individual study estimates from 111 unique cohort studies were
included. Overall, the risk increase of colorectal cancer is 12% for each 100
g/day increase of red and processed meat intake (95% CI = 4-21%, I2=70%,
pheterogeneity (ph)<0.01) and 7% for 10 g/day increase of ethanol intake in
alcoholic drinks (95% CI = 5-9%, I2=25%, ph = 0.21). Colorectal cancer risk
decrease in 17% for each 90g/day increase of whole grains (95% CI = 11-21%, I2 =
0%, ph = 0.30, 6 studies) and 13% for each 400 g/day increase of dairy products
intake (95% CI = 10-17%, I2 = 18%, ph = 0.27, 10 studies). Inverse associations
were also observed for vegetables intake (RR per 100 g/day =0.98 (95% CI = 0.96
0.99, I2=0%, ph = 0.48, 11 studies) and for fish intake (RR for 100 g/day = 0.89
(95% CI = 0.80-0.99, I2=0%, ph = 0.52, 11 studies), that were weak for vegetables
and driven by one study for fish. Intakes of fruits, coffee, tea, cheese, poultry
and legumes were not associated with colorectal cancer risk. Conclusions: Our
results reinforce the evidence that high intake of red and processed meat and
alcohol increase the risk of colorectal cancer. Milk and whole grains may have a
protective role against colorectal cancer. The evidence for vegetables and fish
was less convincing.
PMID- 28407092
TI - Letter to the Editor.
PMID- 28407091
TI - Brassinosteroid Involvement in Arabidopsis thaliana Stomatal Opening.
AB - Stomata within the plant epidermis regulate CO2 uptake for photosynthesis and
water loss through transpiration. Stomatal opening in Arabidopsis thaliana is
determined by various factors, including blue light as a signal and multiple
phytohormones. Plasma membrane transporters, including H+-ATPase, K+ channels and
anion channels in guard cells, mediate these processes, and the activities and
expression levels of these components determine stomatal aperture. However, the
regulatory mechanisms involved in these processes are not fully understood. In
this study, we used infrared thermography to isolate a mutant defective in
stomatal opening in response to light. The causative mutation was identified as
an allele of the brassinosteroid (BR) biosynthetic mutant dwarf5. Guard cells
from this mutant exhibited normal H+-ATPase activity in response to blue light,
but showed reduced K+ accumulation and inward-rectifying K+ (K+in) channel
activity as a consequence of decreased expression of major K+in channel genes.
Consistent with these results, another BR biosynthetic mutant, det2-1, and a BR
receptor mutant, bri1-6, exhibited reduced blue light-dependent stomatal opening.
Furthermore, application of BR to the hydroponic culture medium completely
restored stomatal opening in dwarf5 and det2-1 but not in bri1-6. However,
application of BR to the epidermis of dwarf5 did not restore stomatal response.
From these results, we conclude that endogenous BR acts in a long-term manner and
is required in guard cells with the ability to open stomata in response to light,
probably through regulation of K+in channel activity.
PMID- 28407094
TI - Pay-for-performance reduces healthcare spending and improves quality of care:
Analysis of target and non-target obstetrics and gynecology surgeries.
AB - Objective: In Korea, the Value Incentive Program (VIP) was first applied to
selected clinical conditions in 2007 to evaluate the performance of medical
institutes. We examined whether the condition-specific performance of the VIP
resulted in measurable improvement in quality of care and in reduced medical
costs. Design: Population-based retrospective observational study. Setting: We
used two data set including the results of quality assessment and hospitalization
data from National Health Claim data from 2011 to 2014. Participants:
Participants who were admitted to the hospital for obstetrics and gynecology were
included. A total of 535 289 hospitalizations were included in our analysis.
Methods: We used a generalized estimating equation (GEE) model to identify
associations between the quality assessment and length of stay (LOS). A GEE model
based on a gamma distribution was used to evaluate medical cost. The Poisson
regression analysis was used to evaluate readmission. Main Outcome Measures: The
outcome variables included LOS, medical costs and readmission within 30 days.
Results: Higher condition-specific performance by VIP participants was associated
with shorter LOSs, decreases in medical cost, and lower within 30-day readmission
rates for target and non-target surgeries. LOS and readmission within 30 days
were different by change in quality assessment at each medical institute.
Conclusions: Our findings contribute to the body of evidence used by policy
makers for expansion and development of the VIP. The study revealed the positive
effects of quality assessment on quality of care. To reduce the between-institute
quality gap, alternative strategies are needed for medical institutes that had
low performance.
PMID- 28407093
TI - Non-Random Inversion Landscapes in Prokaryotic Genomes Are Shaped by
Heterogeneous Selection Pressures.
AB - Inversions are a major contributor to structural genome evolution in prokaryotes.
Here, using a novel alignment-based method, we systematically compare 1,651
bacterial and 98 archaeal genomes to show that inversion landscapes are
frequently biased toward (symmetric) inversions around the origin-terminus axis.
However, symmetric inversion bias is not a universal feature of prokaryotic
genome evolution but varies considerably across clades. At the extremes,
inversion landscapes in Bacillus-Clostridium and Actinobacteria are dominated by
symmetric inversions, while there is little or no systematic bias favoring
symmetric rearrangements in archaea with a single origin of replication. Within
clades, we find strong but clade-specific relationships between symmetric
inversion bias and different features of adaptive genome architecture, including
the distance of essential genes to the origin of replication and the preferential
localization of genes on the leading strand. We suggest that heterogeneous
selection pressures have converged to produce similar patterns of structural
genome evolution across prokaryotes.
PMID- 28407096
TI - Procalcitonin: The Right Answer but to Which Question?
PMID- 28407095
TI - Genetic and environmental risk factors for rheumatoid arthritis in a UK African
ancestry population: the GENRA case-control study.
AB - Objectives: To evaluate whether genetic and environmental factors associated with
RA in European and Asian ancestry populations are also associated with RA in
African ancestry individuals. Methods: A case-control study was undertaken in 197
RA cases and 868 controls of African ancestry (Black African, Black Caribbean or
Black British ethnicity) from South London. Smoking and alcohol consumption data
at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping
Array) and human leukocyte antigen (HLA) alleles imputed. The following
European/Asian RA susceptibility factors were tested: 99 genome-wide loci
combined into a genetic risk score; HLA region [20 haplotypes; shared epitope
(SE)]; smoking; and alcohol consumption. The SE was tested for its association
with radiological erosions. Logistic regression models were used, including
ancestry-informative principal components, to control for admixture. Results:
European/Asian susceptibility loci were associated with RA in African ancestry
individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53
(95% CI: 1.31, 1.79; P = 1.3 * 10 - 7 ). HLA haplotype ORs in European and
African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56,
0.94; P = 1.1 * 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82;
P = 4.6 * 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P
= 2.7 * 10 - 5 ) RA risk in African ancestry individuals. The SE was associated
with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 * 10 - 3 ). Conclusion:
Gene-environment RA risk factors identified in European/Asian ancestry
populations are relevant in African ancestry individuals. As modern statistical
methods facilitate analysing ancestrally diverse populations, future genetic
studies should incorporate African ancestry individuals to ensure their
implications for precision medicine are universally applicable.
PMID- 28407098
TI - Misguided diversions: coronary artery fistulae.
PMID- 28407097
TI - miRCat2: accurate prediction of plant and animal microRNAs from next-generation
sequencing datasets.
AB - Motivation: MicroRNAs are a class of ~21-22 nt small RNAs which are excised from
a stable hairpin-like secondary structure. They have important gene regulatory
functions and are involved in many pathways including developmental timing,
organogenesis and development in eukaryotes. There are several computational
tools for miRNA detection from next-generation sequencing datasets. However, many
of these tools suffer from high false positive and false negative rates. Here we
present a novel miRNA prediction algorithm, miRCat2. miRCat2 incorporates a new
entropy-based approach to detect miRNA loci, which is designed to cope with the
high sequencing depth of current next-generation sequencing datasets. It has a
user-friendly interface and produces graphical representations of the hairpin
structure and plots depicting the alignment of sequences on the secondary
structure. Results: We test miRCat2 on a number of animal and plant datasets and
present a comparative analysis with miRCat, miRDeep2, miRPlant and miReap. We
also use mutants in the miRNA biogenesis pathway to evaluate the predictions of
these tools. Results indicate that miRCat2 has an improved accuracy compared with
other methods tested. Moreover, miRCat2 predicts several new miRNAs that are
differentially expressed in wild-type versus mutants in the miRNA biogenesis
pathway. Availability and Implementation: miRCat2 is part of the UEA small RNA
Workbench and is freely available from http://srna-workbench.cmp.uea.ac.uk/.
Contact: v.moulton@uea.ac.uk or s.moxon@uea.ac.uk. Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 28407099
TI - Discontinuation of tofacitinib after achieving low disease activity in patients
with rheumatoid arthritis: a multicentre, observational study.
AB - Objective: To determine whether tofacitinib can be discontinued in patients with
RA who achieve low disease activity (LDA). Methods: RA patients with LDA after
tofacitinib treatment in a phase III and long-term extension study were enrolled
in this multicentre, non-randomized, open, prospective, observational study. The
decision of discontinuation or continuation of tofacitinib was determined based
on patient-physician decision making with informed consent. The primary endpoint
was the proportion of patients who remained tofacitinib-free at post-treatment
week 52. Clinical outcome was compared between those who continued and those who
discontinued tofacitinib. The last observation carried forward method was used
for patients who could not discontinue tofacitinib before week 52. Results: Of 64
patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment
week 52, 20 of the 54 patients (37%) of the discontinuation group remained
tofacitinib-free without disease flare. Disease activity at post-treatment week
52 was higher in the discontinuation group than the continuation group. Among the
discontinuation group, the RF titre at baseline was significantly lower in
patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml).
In fact, a higher proportion of patients with lower RF remained tofacitinib-free
at week 52 compared with those with higher RF at baseline. In patients who could
not achieve tofacitinib-free status, re-initiation of tofacitinib or other
biologics improved disease activity. Conclusion: It is possible to discontinue
tofacitinib without flare in about a third of patients with RA. A low RF predicts
maintenance of LDA after discontinuation of tofacitinib.
PMID- 28407100
TI - SeqA structures behind Escherichia coli replication forks affect replication
elongation and restart mechanisms.
AB - The SeqA protein binds hemi-methylated GATC sites and forms structures that
sequester newly replicated origins and trail the replication forks. Cells that
lack SeqA display signs of replication fork disintegration. The broken forks
could arise because of over-initiation (the launching of too many forks) or lack
of dynamic SeqA structures trailing the forks. To confirm one or both of these
possible mechanisms, we compared two seqA mutants with the oriCm3 mutant. The
oriCm3 mutant over-initiates because of a lack of origin sequestration but has
wild-type SeqA protein. Cells with nonfunctional SeqA, but not oriCm3 mutant
cells, had problems with replication elongation, were highly dependent on
homologous recombination, and exhibited extensive chromosome fragmentation. The
results indicate that replication forks frequently break in the absence of SeqA
function and that the broken forks are rescued by homologous recombination. We
suggest that SeqA may act in two ways to stabilize replication forks: (i) by
enabling vital replication fork repair and restarting reactions and (ii) by
preventing replication fork rear-end collisions.
PMID- 28407102
TI - The PERFORM project: using performing arts to increase engagement and
understanding of science.
AB - This commentary describes some of the current challenges for science education in
the UK and how an EU educational project (PERFORM) is seeking to use performing
arts to engage young people with science, its values and the processes of
research.
PMID- 28407103
TI - A network of cis and trans interactions is required for ParB spreading.
AB - Most bacteria utilize the highly conserved parABS partitioning system in plasmid
and chromosome segregation. This system depends on a DNA-binding protein ParB,
which binds specifically to the centromere DNA sequence parS and to adjacent non
specific DNA over multiple kilobases in a phenomenon called spreading. Previous
single-molecule experiments in combination with genetic, biochemical and
computational studies have argued that ParB spreading requires cooperative
interactions between ParB dimers including DNA bridging and possible nearest
neighbor interactions. A recent structure of a ParB homolog co-crystallized with
parS revealed that ParB dimers tetramerize to form a higher order nucleoprotein
complex. Using this structure as a guide, we systematically ablated a series of
proposed intermolecular interactions in the Bacillus subtilis ParB (BsSpo0J) and
characterized their effect on spreading using both in vivo and in vitro assays.
In particular, we measured DNA compaction mediated by BsSpo0J using a recently
developed single-molecule method to simultaneously visualize protein binding on
single DNA molecules and changes in DNA conformation without protein labeling.
Our results indicate that residues acting as hubs for multiple interactions
frequently led to the most severe spreading defects when mutated, and that a
network of both cis and trans interactions between ParB dimers is necessary for
spreading.
PMID- 28407104
TI - Minimally invasive or conventional edge-to-edge repair for severe mitral
regurgitation due to bileaflet prolapse in Barlow's disease: does the surgical
approach have an impact on the long-term results?
AB - OBJECTIVES: To evaluate whether the adoption of a right minithoracotomy operative
approach had an impact on the long-term results of edge-to-edge (EE) repair
compared to conventional sternotomy in patients with Barlow's disease and
bileaflet prolapse. METHODS: We assessed the long-term results of 104 patients
with Barlow's disease treated with a minimally invasive EE technique. An equal
number of patients had a conventional median sternotomy EE repair for the same
disease and were used as a control group. The inverse probability of treatment
weighting was used to create comparable distributions of the covariates that were
significantly different at baseline in the two groups. We performed a comparative
analysis of the groups. RESULTS: No hospital deaths were observed. Follow-up was
99.5% complete (median 11.3 years). The cumulative incidence function (CIF) of
cardiac death at 12 years, with noncardiac death as a competing risk, showed no
difference between the two groups ( P = 0.87). At 12 years, the CIF of recurrent
MR >= 3+, with death as the competing risk, was 7% in the sternotomy group and 5%
in the minimally invasive group ( P = 0.30), and the CIF of recurrence of MR >=
2+ was 15 and 14%, respectively ( P = 0.63). The type of surgical approach was
not a predictor of cardiac death, reoperation, recurrent MR >= 3+ or recurrent MR
>= 2+. CONCLUSIONS: A minimally invasive approach does not have a negative impact
on the effectiveness and long-term durability of the EE repair for bileaflet
prolapse in Barlow's disease. Long-term outcomes are excellent, and valvular
performance remains stable over time with no evidence of mitral stenosis.
PMID- 28407101
TI - Early Life Exposures and Adult Cancer Risk.
AB - Very little is known about the influence of early life exposures on adult cancer
risk. The purpose of this narrative review was to summarize the epidemiologic
evidence relating early life tobacco use, obesity, diet, and physical activity to
adult cancer risk; describe relevant theoretical frameworks and methodological
strategies for studying early life exposures; and discuss policies and research
initiatives focused on early life. Our findings suggest that in utero exposures
may indirectly influence cancer risk by modifying biological pathways associated
with carcinogenesis; however, more research is needed to firmly establish these
associations. Initiation of exposures during childhood and adolescence may impact
cancer risk by increasing duration and lifetime exposure to carcinogens and/or by
acting during critical developmental periods. To expand the evidence base, we
encourage the use of life course frameworks, causal inference methods such as
Mendelian randomization, and statistical approaches such as group-based
trajectory modeling in future studies. Further, we emphasize the need for
objective exposure biomarkers and valid surrogate endpoints to reduce
misclassification. With the exception of tobacco use, there is insufficient
evidence to support the development of new cancer prevention policies; however,
we highlight existing policies that may reduce the burden of these modifiable
risk factors in early life.
PMID- 28407105
TI - Preliminary Epidemiologic Assessment of Human Infections With Highly Pathogenic
Avian Influenza A(H5N6) Virus, China.
AB - Background: Since 2014, 17 human cases of infection with the newly emerged highly
pathogenic avian influenza A(H5N6) virus have been identified in China to date.
The epidemiologic characteristics of laboratory-confirmed A(H5N6) cases were
compared to A(H5N1) and A(H7N9) cases in mainland China. Methods: Data on
laboratory-confirmed H5N6, H5N1, and H7N9 cases identified in mainland China were
analyzed to compare epidemiologic characteristics and clinical severity. Severity
of confirmed H5N6, H5N1 and H7N9 cases was estimated based on the risk of severe
outcomes in hospitalized cases. Results: H5N6 cases were older than H5N1 cases
with a higher prevalence of underlying medical conditions but younger than H7N9
cases. Epidemiological time-to-event distributions were similar among cases
infected with the 3 viruses. In comparison to a fatality risk of 70% (30/43) for
hospitalized H5N1 cases and 41% (319/782) for hospitalized H7N9 cases, 12 (75%)
out of the 16 hospitalized H5N6 cases were fatal, and 15 (94%) required
mechanical ventilation. Conclusion: Similar epidemiologic characteristics and
high severity were observed in cases of H5N6 and H5N1 virus infection, whereas
severity of H7N9 virus infections appeared lower. Continued surveillance of human
infections with avian influenza A viruses remains an essential component of
pandemic influenza preparedness.
PMID- 28407106
TI - Rapid Decline in HIV Incidence Among Persons Who Inject Drugs During a Fast-Track
Combination Prevention Program After an HIV Outbreak in Athens.
AB - Background.: A "seek-test-treat" intervention (ARISTOTLE) was implemented in
response to an outbreak of human immunodeficiency virus (HIV) infection among
persons who inject drugs (PWID) in Athens. We assess trends in HIV incidence,
prevalence, risk behaviors and access to prevention/treatment. Methods.: Methods
included behavioral data collection, provision of injection equipment, HIV
testing, linkage to opioid substitution treatment (OST) programs and HIV care
during 5 rounds of respondent-driven sampling (2012-2013). HIV incidence was
estimated from observed seroconversions. Results.: Estimated coverage of the
target population was 88% (71%-100%; 7113 questionnaires/blood samples from 3320
PWID). The prevalence of HIV infection was 16.5%. The incidence per 100 person
years decreased from 7.8 (95% confidence interval, 4.6-13.1) (2012) to 1.7 (0.55
5.31) (2013; P for trend = .001). Risk factors for seroconversion were frequency
of injection, homelessness, and history of imprisonment. Injection at least once
daily declined from 45.2% to 18.8% (P < .001) and from 36.8% to 26.0% (P = .007)
for sharing syringes, and the proportion of undiagnosed HIV infection declined
from 84.3% to 15.0% (P < .001). Current OST increased from 12.2% to 27.7% (P <
.001), and 48.4% of unlinked seropositive participants were linked to HIV care
through 2013. Repeat participants reported higher rates of adequate syringe
coverage, linkage to HIV care and OST. Conclusions.: Multiple evidence-based
interventions delivered through rapid recruitment in a large proportion of the
population of PWID are likely to have helped mitigate this HIV outbreak.
PMID- 28407107
TI - Phylogeography of Sophora moorcroftiana Supports Wu's Hypothesis on the Origin of
Tibetan Alpine Flora.
AB - Wu hypothesized that the Tibetan flora originated mostly from the paleotropical
Tertiary flora in the Hengduan Mountains by adapting to the cold and arid
environments associated with the strong uplift of the Qinghai-Tibet Plateau
(QTP). Here, we combine the phylogeographic history of Sophora moorcroftiana with
that of Sophora davidii to explore the speciation of S. moorcroftiana to test
this hypothesis. We collected 151 individuals from 17 populations and sequenced 2
chloroplast fragments and the internal transcribed spacer of rDNA. Five
chlorotypes and 9 ribotypes were detected but no significant phylogeographic
structure was revealed. The integrated results of phylogeographic studies of
these 2 species clearly support the progenitor-derivative relationship between
them. We infer that the western peripheral population of S. davidii migrated
westwards from the Hengduan Mountains to the middle reaches of the Yarlung Zangbo
River and differentiated from its ancestor in the process of adaptation to
increasingly cold and arid environments with the uplift of the QTP and finally
evolved into S. moorcroftiana during the Late Pliocene. In addition, our findings
shed light on the idea that natural selection, as imposed by climate
differentiation (especially mean diurnal range and precipitation seasonality),
directly drove this peripatric speciation event after geographic isolation. The
speciation of S. moorcroftiana is a strong case supporting Wu's hypothesis about
the origin of Tibet's flora.
PMID- 28407108
TI - Realizing the promise of The Partnership for Maternal, Newborn and Child Health.
AB - Reflecting on Storeng and Behague ("Lives in the balance": the politics of
integration in the Partnership for Maternal, Newborn and Child Health. Health
Policy and Planning Storeng and Behague (2016).) historical ethnography of the
Partnership for Maternal, Newborn and Child Health (PMNCH), this commentary
provides a more current account of PMNCH's trajectory since its inception in
2005. It highlights PMNCH's distinct characteristics and how it is positioned to
play an instrumental role in the current global health landscape.
PMID- 28407109
TI - CHA2DS2-VASc score for ischaemic stroke risk stratification in patients with
chronic obstructive pulmonary disease with and without atrial fibrillation: a
nationwide cohort study.
AB - Aims: We conducted this nationwide cohort study to identify the performance of
CHA2DS2-VASc score for ischaemic stroke risk stratification in chronic
obstructive pulmonary disease (COPD) patients whether they had comorbid atrial
fibrillation (AF) or not. Methods and results: Using the longitudinal health
insurance database 2000, patients aged >=20 years with newly diagnosed COPD from
2000 to 2011 with at least three claims for outpatient and/or hospitalization
visits were identified. A total of 1492 COPD patients with AF and 50 343 COPD
patients without AF were included in this study. We calculated the CHA2DS2-VASc
score-specific incidence density rates of ischaemic stroke with person-years in
each cohort. Cox models were conducted to calculate hazard ratios (HRs) and 95%
confidence intervals (CIs) of ischaemic stroke risk in COPD patients with and
without concomitant AF. The predictive performance of CHA2DS2-VASc score with
regard to ischaemic stroke events was assessed using area under the receiver
operating characteristic curve (C-statistic). COPD patients with a higher CHA2DS2
VASc score were more likely to develop ischaemic stroke whether or not AF was
present. Moreover, the C-statistics of CHA2DS2-VASc score in predicting ischaemic
stroke in COPD patients with and without AF were 0.58 (95% CI = 0.55-0.62) and
0.71(95% CI = 0.70-0.72), respectively. Conclusions: Our study is the first to
show that the performance of CHA2DS2-VASc score in predicting ischaemic stroke is
better for COPD patients without AF than for COPD patients with AF.
PMID- 28407111
TI - Road injuries, health burden, but not fatalities make 12- to 17-year olds a high
risk group in the Netherlands.
AB - Background: To explore the impact of road injuries for different age groups, this
study compares the health burden of road injuries in young adolescents-12 to 17
years of age-to those for older age groups. Young adolescents are
underrepresented in road fatalities. However, their inexperience, developmental
stage and use of bicycles may expose them to high levels of road risk, but their
physical resilience may help them survive injuries which in older age groups
would be fatal. Methods: To assess the impact of injuries compared with death,
this study assessed by age group the health burden expressed in disability
adjusted life years; years of life lost plus years lived with disability. Its
analyses make use of existing data bases on road fatalities, serious injuries
(maximum abbreviated injury score 2 or more), travel, life expectancy and
disability weights. Results: For young adolescents, seriously injuries per
distance travelled (injury risk) were higher than for any other age group, except
for the elderly (75+). This was further amplified when health burden was taken
into account, showing these young adolescents to be responsible for 15% of the
total health burden associated with road crashes. Conclusions: These results
justify extra efforts to improve the understanding and prevention of injury-only
crashes among young adolescents.
PMID- 28407112
TI - Collaborating to develop joint water, sanitation and hygiene (WASH) and neglected
tropical disease (NTD) sector monitoring: an expert consultation.
AB - Background: Joint monitoring between the water, sanitation and hygiene (WASH) and
neglected tropical disease (NTD) sectors presents an opportunity for enhanced
collaboration and progress towards shared objectives. Taking forward outputs from
global WASH and NTD Roundtables, we engaged experts in a consultative process of
identifying measurable priority indicators for joint monitoring. Methods: We used
a Delphi method for conducting expert consultation and developing consensus.
Experts were invited to participate through purposive and snowball sampling, and
open solicitation at key sector meetings. Participating WASH and NTDs experts
represented a diversity of interest groups, including NTD and WASH field staff
and government stakeholders from endemic countries, bilateral and multilateral
development agencies, non-governmental organizations, and academic institutions.
Four rounds of consultation were conducted via online surveys. Results: Between
55 and 69 experts participated in each round of consultation. Seven core
measurable indicators emerged as priorities for inclusion in joint monitoring for
the NTD sector. Conclusion: Our findings provide insight on the development and
implementation of joint monitoring frameworks that can be integrated into
existing programme level monitoring.
PMID- 28407110
TI - Prognostic and predictive value of primary tumour side in patients with RAS wild
type metastatic colorectal cancer treated with chemotherapy and EGFR directed
antibodies in six randomized trials.
AB - Background: There is increasing evidence that metastatic colorectal cancer (mCRC)
is a genetically heterogeneous disease and that tumours arising from different
sides of the colon (left versus right) have different clinical outcomes.
Furthermore, previous analyses comparing the activity of different classes of
targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that
primary tumour location (side), might be both prognostic and predictive for
clinical outcome. Methods: This retrospective analysis investigated the
prognostic and predictive influence of the localization of the primary tumour in
patients with unresectable RAS wt mCRC included in six randomized trials
(CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy
plus EGFR antibody therapy (experimental arm) with chemotherapy or chemotherapy
and bevacizumab (control arms). Hazard ratios (HRs) and 95% confidence intervals
(CIs) for overall survival (OS) and progression-free survival (PFS) for patients
with left-sided versus right-sided tumours, and odds ratios (ORs) for objective
response rate (ORR) were estimated by pooling individual study HRs/ORs. The
predictive value was evaluated by pooling study interaction between treatment
effect and tumour side. Results: Primary tumour location and RAS mutation status
were available for 2159 of the 5760 patients (37.5%) randomized across the 6
trials, 515 right-sided and 1644 left-sided. A significantly worse prognosis was
observed for patients with right-sided tumours compared with those with left
sided tumours in both the pooled control and experimental arms for OS [HRs = 2.03
(95% CI: 1.69-2.42) and 1.38 (1.17-1.63), respectively], PFS [HRs = 1.59 (1.34
1.88) and 1.25 (1.06-1.47)], and ORR [ORs = 0.38 (0.28-0.50) and 0.56 (0.43
0.73)]. In terms of a predictive effect, a significant benefit for chemotherapy
plus EGFR antibody therapy was observed in patients with left-sided tumours [HRs
= 0.75 (0.67-0.84) and 0.78 (0.70-0.87) for OS and PFS, respectively] compared
with no significant benefit for those with right-sided tumours [HRs = 1.12 (0.87
1.45) and 1.12 (0.87-1.44) for OS and PFS, respectively; P value for interaction
<0.001 and 0.002, respectively]. For ORR, there was a trend (P value for
interaction = 0.07) towards a greater benefit for chemotherapy plus EGFR antibody
therapy in the patients with left-sided tumours [OR = 2.12 (1.77-2.55)] compared
with those with right-sided tumours [OR = 1.47 (0.94-2.29)]. Exclusion of the
unique phase II trial or the unique second-line trial had no impact on the
results. The predictive effect on PFS may depend of the type of EGFR antibody
therapy and on the presence or absence of bevacizumab in the control arm.
Conclusion: This pooled analysis showed a worse prognosis for OS, PFS and ORR for
patients with right-sided tumours compared with those with left-sided tumours in
patients with RAS wt mCRC and a predictive effect of tumour side, with a greater
effect of chemotherapy plus EGFR antibody therapy compared with chemotherapy or
chemotherapy and bevacizumab, the effect being greatest in patients with left
sided tumours. These predictive results should be interpreted with caution due to
the retrospective nature of the analysis, which was carried out on subpopulations
of patients included in these trials, and because none of these studies
contemplated a full treatment sequence strategy.
PMID- 28407113
TI - A new promoter element associated with daily time keeping in Drosophila.
AB - Circadian clocks are autonomous daily timekeeping mechanisms that allow organisms
to adapt to environmental rhythms as well as temporally organize biological
functions. Clock-controlled timekeeping involves extensive regulation of rhythmic
gene expression. To date, relatively few clock-associated promoter elements have
been identified and characterized. In an unbiased search of core clock gene
promoters from 12 species of Drosophila, we discovered a 29-bp consensus sequence
that we designated as the Clock-Associated Transcriptional Activation Cassette or
'CATAC'. To experimentally address the spatiotemporal expression information
associated with this element, we generated constructs with four separate native
CATAC elements upstream of a basal promoter driving expression of either the
yeast Gal4 or firefly luciferase reporter genes. Reporter assays showed that
presence of wild-type, but not mutated CATAC elements, imparted increased
expression levels as well as rhythmic regulation. Part of the CATAC consensus
sequence resembles the E-box binding site for the core circadian transcription
factor CLOCK/CYCLE (CLK/CYC), and CATAC-mediated expression rhythms are lost in
the presence of null mutations in either cyc or the gene encoding the CLK/CYC
inhibitor, period (per). Nevertheless, our results indicate that CATAC's enhancer
function persists in the absence of CLK/CYC. Thus, CATAC represents a novel cis
regulatory element encoding clock-controlled regulation.
PMID- 28407114
TI - ESTABLISHMENT OF DETAILED EYE MODEL OF ADULT CHINESE MALE AND DOSE CONVERSION
COEFFICIENTS CALCULATION UNDER NEUTRON EXPOSURE.
AB - The human eye lens is sensitive to radiation. ICRP-118 publication recommended a
reduction of the occupational annual equivalent dose limit from 150 to 20 mSv,
averaged over defined periods of 5 y. Therefore, it is very important to build a
detailed eye model for the accurate dose assessment and radiation risk evaluation
of eye lens. In this work, a detailed eye model was build based on the
characteristic anatomic parameters of the Chinese adult male. This eye model
includes seven main structures, which are scleral, choroid, lens, iris, cornea,
vitreous body and aqueous humor. The lens was divided into sensitive volume and
insensitive volume based on different cell populations. The detailed eye model
was incorporated into the converted polygon-mesh version of the Chinese reference
adult male whole-body surface model. After the incorporation, dose conversion
coefficients for the eye lens were calculated for neutron exposure at AP, PA and
LAT geometries with Geant4, the neutron energies were from 0.001 eV to 10 MeV.
The calculated lens dose coefficients were compared with those of ICRP-116
publication. Significant differences up to 97.47% were found at PA geometry. This
could mainly be attributed to the different geometry characteristic of eye model
and parameters of head in different phantom between the present work and ICRP-116
publication.
PMID- 28407115
TI - A new era for collaboration?
PMID- 28407117
TI - NNAlign: a platform to construct and evaluate artificial neural network models of
receptor-ligand interactions.
AB - Peptides are extensively used to characterize functional or (linear) structural
aspects of receptor-ligand interactions in biological systems, e.g. SH2, SH3, PDZ
peptide-recognition domains, the MHC membrane receptors and enzymes such as
kinases and phosphatases. NNAlign is a method for the identification of such
linear motifs in biological sequences. The algorithm aligns the amino acid or
nucleotide sequences provided as training set, and generates a model of the
sequence motif detected in the data. The webserver allows setting up cross
validation experiments to estimate the performance of the model, as well as
evaluations on independent data. Many features of the training sequences can be
encoded as input, and the network architecture is highly customizable. The
results returned by the server include a graphical representation of the motif
identified by the method, performance values and a downloadable model that can be
applied to scan protein sequences for occurrence of the motif. While its
performance for the characterization of peptide-MHC interactions is widely
documented, we extended NNAlign to be applicable to other receptor-ligand systems
as well. Version 2.0 supports alignments with insertions and deletions, encoding
of receptor pseudo-sequences, and custom alphabets for the training sequences.
The server is available at http://www.cbs.dtu.dk/services/NNAlign-2.0.
PMID- 28407116
TI - Lethal aplastic anemia caused by dual immune checkpoint blockade in metastatic
melanoma.
PMID- 28407118
TI - Voriconazole Dosing in Children Younger Than 3 Years Undergoing Cancer
Chemotherapy or Hematopoietic Stem Cell Transplantation.
AB - There are limited pediatric population pharmacokinetic data for voriconazole
dosing, particularly in younger children. In a cohort of 34 patients younger than
3 years receiving voriconazole, the majority (n = 23, 68%) had a low initial
serum concentration <1 mg/L. Among 23 children <2 years old, 19 (83%) had an
initial trough <1 mg/L. There was large intra- and interindividual variability in
trough levels. Dosing also varied from 3.3 to 19.6 mg/kg per dose. Only 2 of 34
patients had a documented adverse drug reaction attributable to voriconazole.
More data are needed to establish optimal dosing in very young children.
PMID- 28407119
TI - A barley UDP-glucosyltransferase inactivates nivalenol and provides Fusarium Head
Blight resistance in transgenic wheat.
AB - Fusarium Head Blight is a disease of cereal crops that causes severe yield losses
and mycotoxin contamination of grain. The main causal pathogen, Fusarium
graminearum, produces the trichothecene toxins deoxynivalenol or nivalenol as
virulence factors. Nivalenol-producing isolates are most prevalent in Asia but co
exist with deoxynivalenol producers in lower frequency in North America and
Europe. Previous studies identified a barley UDP-glucosyltransferase, HvUGT13248,
that efficiently detoxifies deoxynivalenol, and when expressed in transgenic
wheat results in high levels of type II resistance against deoxynivalenol
producing F. graminearum. Here we show that HvUGT13248 is also capable of
converting nivalenol into the non-toxic nivalenol-3-O-beta-d-glucoside. We
describe the enzymatic preparation of a nivalenol-glucoside standard and its use
in development of an analytical method to detect the nivalenol-glucoside
conjugate. Recombinant Escherichia coli expressing HvUGT13248 glycosylates
nivalenol more efficiently than deoxynivalenol. Overexpression in yeast,
Arabidopsis thaliana, and wheat leads to increased nivalenol resistance.
Increased ability to convert nivalenol to nivalenol-glucoside was observed in
transgenic wheat, which also exhibits type II resistance to a nivalenol-producing
F. graminearum strain. Our results demonstrate the HvUGT13248 can act to detoxify
deoxynivalenol and nivalenol and provide resistance to deoxynivalenol- and
nivalenol-producing Fusarium.
PMID- 28407120
TI - Biological versus mechanical Bentall procedure for aortic root replacement: a
propensity score analysis of a consecutive series of 1112 patients.
AB - OBJECTIVES: In this study, a propensity-matching analysis was used to compare
biological versus mechanical composite valve graft implantation for early
mortality and morbidities and for late complications including the need for
aortic reintervention. METHODS: Between 1978 and 2011, 1112 consecutive patients
underwent a complete aortic root replacement using either a biological Bentall
(BB, n = 356) or a mechanical Bentall (MB, n = 756) valve conduit. Preoperative
data were stratified according to the type of valve graft, and treatment bias was
addressed by propensity score analysis. RESULTS: Two homogeneous groups of 138
patients were obtained. Hospital mortality between them was comparable (MB = 7.2%
and BB = 5.8%, P = 0.6). They also had similar results after a mean follow-up
time of 40 +/- 38 months. Propensity-adjusted Cox-regression analysis showed no
relationship between the type of prosthesis and all-cause mortality at follow-up
(hazards ratio: 0.88; 95% confidence interval: 0.50-2.14; P = 0.4). Freedom from
proximal aortic reintervention at 1, 5 and 7 years was 99.1 +/- 0.9% in the MB
group compared with 98.4 +/- 1.1%, 93.0 +/- 3.2% and 93.0 +/- 3.2% in the BB
group (long-rank P = 0.07). CONCLUSIONS: The Bentall procedure is a safe and
reproducible treatment for ascending aorta pathologies. The choice of either a
mechanical or a biological valve graft seems to have no influence on early and
late midterm adverse outcomes including need for aortic reinterventions.
PMID- 28407121
TI - Urea and chronic kidney disease: the comeback of the century? (in uraemia
research).
AB - Urea, a marker of uraemic retention in chronic kidney disease (CKD) and of
adequacy of intradialytic solute removal, has traditionally been considered to be
biologically inert. However, a number of recent experimental data suggest that
urea is toxic at concentrations representative for CKD. First of all, at least
five studies indicate that urea itself induces molecular changes related to
insulin resistance, free radical production, apoptosis and disruption of the
protective intestinal barrier. Second, urea is at the origin of the generation of
cyanate, ammonia and carbamylated compounds, which as such all have been linked
to biological changes. Especially carbamylation has been held responsible for
post-translational protein modifications that are involved in atherogenesis and
other functional changes. In observational clinical studies, these carbamylated
compounds were associated with cardiovascular and overall morbidity and
mortality. These findings shed new light on the validity of Kt/Vurea as a marker
of dialysis adequacy. Yet, also the views that the kinetics of urea are not
representative of the kinetics of several other uraemic retention solutes, and
that urea cannot be held responsible for all complex metabolic and clinical
changes responsible for the uraemic syndrome, still remain valid. Future efforts
to improve the outcome of patients with CKD might be directed at further
improving removal of solutes implied in the uraemic syndrome, including but not
restricted to urea, also taking into account the impact of the intestine and
(residual) renal function on solute concentration.
PMID- 28407123
TI - Remembering Robert Kane.
PMID- 28407122
TI - Pseudorotaxane formation via the slippage process with chemically cyclized
oligonucleotides.
AB - Circular nucleic acids have been utilized for versatile applications by taking
advantage of the unique characteristic of their circular structure. In our
previous study, we found that the chemically-cyclized ODN (cyODN) with double
tailed parts formed a pseudorotaxane structure with the target via the slippage
process. We now report the investigation of the slippage properties and the
mechanism of the slippage process using six different cyODNs. Our results
indicate that the formation efficiency significantly depend on the temperature,
the ring size, the target length and the mismatched position of the target. The
kinetic studies also showed that this pseudorotaxane formation would proceed via
a non-threaded structure which hybridizes with the target at the double-tailed
parts. In addition, the resulting pseudorotaxanes showed interesting
characteristics unlike the canonical duplex such as the hysteresis loop in the Tm
measurements and the kinetic stabilization by lengthening the target. This
information will be fundamentally important for finding new functions of circular
nucleic acids and elucidating the threading mechanism regarding other synthetic
small molecules and biopolymers.
PMID- 28407124
TI - Structure and Biosynthesis of Branched Wax Compounds on Wild Type and Wax
Biosynthesis Mutants of Arabidopsis thaliana.
AB - The cuticle is a waxy composite that protects the aerial organs of land plans
from non-stomatal water loss. The chemical make-up of the cuticular wax mixture
plays a central role in defining the water barrier, but structure-function
relationships have not been established so far, in part due to gaps in our
understanding of wax structures and biosynthesis. While wax compounds with
saturated, linear hydrocarbon tails have been investigated in detail, very little
is known about compounds with modified aliphatic tails, which comprise
substantial portions of some plant wax mixtures. This study aimed to investigate
the structures, abundances and biosynthesis of branched compounds on the species
for which wax biosynthesis is best understood: Arabidopsis thaliana. Microscale
derivatization, mass spectral interpretation and organic synthesis identified
homologous series of iso-alkanes and iso-alcohols on flowers and leaves,
respectively. These comprised approximately 10-15% of wild type wax mixtures. The
abundances of both branched wax constituents and accompanying unbranched
compounds were reduced on the cer6, cer3 and cer1 mutants but not cer4,
indicating that branched compounds are in part synthesized by the same machinery
as unbranched compounds. In contrast, the abundances of unbranched, but not
branched, wax constituents were reduced on the cer2 and cer26 mutants, suggesting
that the pathways to both types of compounds deviate in later steps of chain
elongation. Finally, the abundances of branched, but not unbranched, wax
compounds were reduced on the cer16 mutant, and the (uncharacterized) CER16
protein may therefore be controlling the relative abundances of iso-alkanes and
iso-alcohols on Arabidopsis surfaces.
PMID- 28407125
TI - Cell fate modification toward the hepatic lineage by extrinsic factors.
AB - The lineage of a somatic cell can be altered by targeting its signaling networks
with small molecules and/or genetically altering the expression of key
transcription factors. Depending on the combination of factors, fibroblasts can
be fully reprogrammed into induced pluripotent stem (iPS) cells or directly
converted into specific cell lineages, bypassing the pluripotent state. The
generation of defined target cells will enormously benefit patients who require
cell transplantation therapy. In the decade, since iPS cells were first
generated, many cell types have been induced from fibroblasts by direct
conversion, including hepatocytes. Converted hepatocyte-like cells have been
shown to repopulate liver tissues after transplantation in mouse liver disease
models, suggesting promise for future application in humans. Thus, to realize
safe and efficient cell transplantation therapy, various methods for generating
hepatocyte-like cells are being developed. In this review, we summarize the
current methods for the generation of hepatocyte-like cells via cell fate
modification using extrinsic factors.
PMID- 28407126
TI - Mitral valve replacement in severely calcified mitral valve annulus: a 10-year
experience.
AB - OBJECTIVES: Severe calcification in the mitral valve annulus is a challenging
problem during mitral valve surgery. We describe our experience with mitral valve
replacement in severely calcified mitral valve without decalcification of the
annulus. METHODS: Between April 2001 and July 2011, 61 patients underwent mitral
valve replacement with severe mitral annulus calcification without
decalcification of the annulus. This retrospective study was performed to assess
the surgical and the long-term postoperative outcomes in this group. RESULTS: The
mean age of the patients was 75.2 +/- 9.2 years. Twenty-four patients (53%) were
in New York Heart Association Class III/IV. Twenty-six patients (58%) had good
left ventricular function. Mean logistic EuroSCORE was 8.75. Isolated mitral
valve replacement was performed in 12 patients (27%). Coronary artery bypass
grafting was done in 13 patients (29%). In-hospital mortality was 4.9% (3
patients). Postoperative morbidity included re-exploration for bleeding in 3
patients (7%) and transient renal impairment in 10 patients (22%). Three patients
required intra-aortic balloon pump (7%) for low cardiac output syndrome. Seven
patients (16%) required permanent pacemaker, and 1 patient (2%) had
thromboembolic event. The 1-year survival was 93.3%, and the 5-year survival was
78.8%. The mean echocardiography follow-up was 40 months. There was no
paravalvular leak detected in any patient in the long-term follow-up. None of the
patients had valve-related reoperation. CONCLUSIONS: Mitral valve replacement
without annular decalcification in severely calcified mitral valve annulus is a
safe and an effective approach and has good long-term outcome.
PMID- 28407127
TI - No clear association between ultrasound remission and health status in rheumatoid
arthritis patients in clinical remission.
AB - Objectives: Although RA patients achieve clinical remission, risk of flare still
exists. Given the association between US synovitis and increased risk of flare,
it is of clinical interest whether these patients report a different health
status. Therefore, our aim was to evaluate the frequency of US remission in RA
patients in clinical remission and to compare the health status of RA patients in
clinical remission with those who were also in US remission. Methods: In a
prospective study, we included 89 RA patients (aged >17 years) treated with a
synthetic DMARD and a TNF inhibitor who were in remission (DAS in 44 joints ?2.4
and swollen joint count ?1). Demographic characteristics, swollen and tender
joints, laboratory variables, US (MCP2-5, PIP2-5, wrists and MTP2-5) and patient
reported outcomes (general health, functional ability, fatigue, depression and
anxiety, pain and morning stiffness) were recorded at two consecutive visits (3
months apart). US remission was defined as grey scale grade ?1 and power Doppler
= 0. Results: At visit 1, 39% of patients were in US remission. At visit 2, 32%
of patients were in US remission. At visit 1, functional ability (HAQ) was scored
lower by patients in US remission (P = 0.029). At visit 2, HAQ scores were
similar (P = 0.928). At visit 2, Hospital Anxiety and Depression Scale anxiety
score and visual analog scale pain were significantly higher in patients in US
remission. Similar levels were found for the other patient-reported outcomes.
Conclusion: One-third of RA patients in clinical remission were in US remission.
In our study population, we could not find a clear association between health
status of RA patients and being in US remission.
PMID- 28407128
TI - The bittersweet taste of tubulo-interstitial glycans.
AB - Recently, interesting work was published by Farrar et al. [1] showing the
interaction of fucosylated glycoproteins on stressed tubular epithelial cells
with collectin-11 leading to complement activation via the lectin route of
complement. This elegant work stimulated us to evaluate the dark side
(bittersweet taste) of tubulo-interstitial glycans in kidney tissue damage. As
will be discussed, glycans not only initiate tubular complement activation but
also orchestrate tubulo-interstitial leucocyte recruitment and growth factor
responses. In this review we restrict ourselves to tubulo-interstitial damage
mainly by proteinuria, ischaemia-reperfusion injury and transplantation, and we
discuss the involvement of endothelial and tubular glycans in atypical and
Escherichia coli-mediated haemolytic uraemic syndrome. As will be seen,
fucosylated, mannosylated, galactosylated and sialylated oligosaccharide
structures along with glycosaminoglycans comprise the most important glycans
related to kidney injury pathways. Up to now, therapeutic interventions in these
glycan-mediated injury pathways are underexplored and warrant further research.
PMID- 28407129
TI - A noninferiority trial comparing a heparin-grafted membrane plus citrate
containing dialysate versus regional citrate anticoagulation: results of the
CiTED study.
AB - Background: Anticoagulation is a prerequisite for successful haemodialysis.
Heparin and low-molecular weight heparins are routinely used despite increased
bleeding risk. Regional citrate anticoagulation (RCA) is efficacious, but is
laborious and may induce metabolic disturbances. Heparin-grafted membranes are
less efficacious. It is not known whether combining citrate-containing dialysate
and a heparin-grafted membrane is a valid anticoagulation strategy. Methods: We
performed a randomized crossover noninferiority trial, with a prespecified
noninferiority threshold of 10% in maintenance dialysis patients ( n = 25). We
compared the combination of citrate-containing dialysate plus a heparin-grafted
membrane [CiTrate and EvoDial (CiTED) protocol] with RCA. The primary endpoint
was completion of dialysis without significant clotting. Secondary endpoints
included time to clotting, achieved Kt / V urea , loss of total cell volume,
venous air chamber clotting score and systemic-ionized calcium concentration.
Results: In total, 1284 sessions were performed according to study protocol, 636
in the CiTED arm and 648 in the RCA arm. The primary outcome of preterm
interruption due to clotting occurred in 36 (5.7%) of sessions in the CiTED arm,
and in 40 (6.2%) sessions in the RCA arm, thereby meeting noninferiority criteria
(P < 0.0001). Most of the clotting events occurred in the fourth hour of
dialysis. Repetitive clotting occurred in four patients in the CiTED arm and one
patient in the RCA arm. Time to preterm interruption due to clotting and achieved
Kt / V urea was not significantly different. Systemic-ionized calcium levels
during treatment were significantly lower in the RCA arm and clinically relevant
hypocalcaemia was noted only in the RCA arm. Conclusion: The combination of
citrate-containing dialysate and a heparin-grafted membrane is a valid
alternative to RCA.
PMID- 28407131
TI - The kidney's role in systemic metabolism-still much to learn.
PMID- 28407130
TI - Impact of end-stage renal disease on glucose metabolism-a matched cohort
analysis.
AB - Background: Renal function is known to affect glucose metabolism. The aim of this
study was to assess glucose metabolism in end-stage renal disease (ESRD) patients
and in matched controls with normal renal function and to delineate its
underlying pathophysiology. Methods: ESRD patients without diabetes mellitus on
the active kidney transplant waiting list of a large European university hospital
were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by
calculating insulin sensitivity and secretion indices. Matched controls with
normal renal function were derived from the TUEF (Tuebingen Family) study cohort,
which includes healthy non-diabetic individuals with an increased risk of
developing type 2 diabetes. Matches were made for (i) gender, age and body mass
index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose
(FPG) and 2-h glucose in OGTT (cohort 2). Results: A total of 107 patients (90 on
haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107
matched controls, were investigated. ESRD patients had significantly lower FPG.
Additional matching for OGTT glucose concentrations revealed significantly lower
insulin sensitivity in ESRD patients than in controls. This finding was abrogated
after adjustment for triglyceride levels. Insulin secretion, however, was
significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C
peptide levels demonstrate higher insulin secretion to be a compensation for
lower insulin sensitivity and not to result from impaired insulin clearance.
Conclusion: Our study is the first to provide metabolic phenotyping in patients
with ESRD and to compare them with matched controls with normal renal function.
Glucose metabolism differs substantially between cohorts, with insulin resistance
and a compensatory increase in insulin secretion in ESRD patients.
PMID- 28407132
TI - Causal mechanism and component causes in Mesoamerican-Sri Lankan nephropathy: the
moderator's view.
AB - Inspired by Conan Doyle's novels, the pro contender of this Polar View undertakes
an elegant exercise in territory common to epidemiology and police investigation
and concludes that cyclic episodes of dehydration in individuals exposed to heavy
work in very hot climates is the cause of Mesoamerican and Sri Lankan
nephropathy. The contender in the opposite camp accepts the idea that dehydration
may play a key role in this condition but highlights a different explanation,
that it is contaminated water used for rehydration that is the eventual cause of
the disease.Causal mechanisms result from the combination of many components,
i.e. conditions or events that are needed for the occurrence of the disease. If
we adopt a global, extended approach to the problem, it is unlikely that cyclic
dehydration is a key component in all cases. While credible in most cases in
Central America, the cyclic dehydration hypothesis fails to explain most cases in
Sri Lanka, where agrochemicals have been implicated as the most likely cause of
this disease. The experience with Balkan nephropathy is an enduring lesson that
full clarification of the causal mechanisms behind endemic nephropathies can be a
decades-long process. Therefore, action to control Mesoamerican and Sri Lankan
nephropathy should not be deferred. Deployable interventions include the
provision of uncontaminated water sources, prevention of dehydration at work
sites and the application of safety procedures for agrochemicals. The joint
application of these interventions will most likely benefit the populations
plagued by this endemic disease.
PMID- 28407133
TI - Con: Mesoamerican nephropathy: is the problem dehydration or rehydration?
AB - In recent years, an increasing number of inhabitants of Central America have
developed a form of chronic kidney disease, now named Mesoamerican nephropathy.
This disease is characterized by minimal proteinuria, hyperuricemia, hypokalemia
and reduced glomerular filtration rate. Histologically the kidneys manifest
tubulointerstitial nephritis. The cause(s) of this disease remain unknown. Some
have proposed that dehydration, in combination with hyperuricemia, may be
primarily responsible for Mesoamerican nephropathy. In this article, I propose
the hypothesis that the disease may be largely due to rehydration with large
amounts of contaminated water, whereas dehydration would play only a contributing
role.
PMID- 28407134
TI - Opponent's comments.
PMID- 28407135
TI - Pro: Heat stress as a potential etiology of Mesoamerican and Sri Lankan
nephropathy: a late night consult with Sherlock Holmes.
AB - Epidemics of chronic kidney disease are now recognized in Central America,
Mexico, India and Sri Lanka, and there is also some evidence that similar
epidemics may be occurring in the USA, Thailand and elsewhere. A common
denominator for each location is manually working outside in extremely hot
environments. Here we review the evidence that the primary etiology may be heat
stress related to repeated subclinical or clinical acute kidney injury that
eventually manifests as chronic kidney disease. In some aspects, the disease may
manifest as subclinical heat stroke, subclinical rhabdomyolysis or a subclinical
tumor lysis syndrome. While toxins could be involved, it would be difficult to
attribute this as a main mechanism, given the wide range of occupations and
geographic regions manifesting this disease. While some of the epidemics may be
due to better reporting, we believe the most important reasons are increasing
heat extremes (heat waves) coupled with hydration with sugary or, less commonly,
alcoholic beverages.
PMID- 28407136
TI - Opponent's comments.
PMID- 28407137
TI - Domain prediction with probabilistic directional context.
AB - Motivation: Protein domain prediction is one of the most powerful approaches for
sequence-based function prediction. Although domain instances are typically
predicted independently of each other, newer approaches have demonstrated
improved performance by rewarding domain pairs that frequently co-occur within
sequences. However, most of these approaches have ignored the order in which
domains preferentially co-occur and have also not modeled domain co-occurrence
probabilistically. Results: We introduce a probabilistic approach for domain
prediction that models 'directional' domain context. Our method is the first to
score all domain pairs within a sequence while taking their order into account,
even for non-sequential domains. We show that our approach extends a previous
Markov model-based approach to additionally score all pairwise terms, and that it
can be interpreted within the context of Markov random fields. We formulate our
underlying combinatorial optimization problem as an integer linear program, and
demonstrate that it can be solved quickly in practice. Finally, we perform
extensive evaluation of domain context methods and demonstrate that incorporating
context increases the number of domain predictions by ~15%, with our approach
dPUC2 (Domain Prediction Using Context) outperforming all competing approaches.
Availability and Implementation: dPUC2 is available at
http://github.com/alexviiia/dpuc2. Contact: mona@cs.princeton.edu. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 28407138
TI - Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study.
AB - Context: Acromegaly has been associated with calcium-phosphate and bone turnover
alterations. Controlled studies of these interactions are sparse. Objective: To
evaluate calcium and bone metabolism in active and treated acromegaly.
Design/Setting/Patients: We conducted a controlled, prospective study at a
tertiary referral center. We studied 22 patients with acromegaly referred for
surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas
referred for surgery (control). Main Outcome Measures: Calcium (serum and urine),
phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D,
bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and
procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor
activator of nuclear factor kappaB ligand (RANK-L) and osteoprotegerin (OPG)] at
baseline and 3 to 6 months after treatment. Results: At baseline, the ACM group
had lower PTH levels than controls (36.3 +/- 13.9 pg/mL vs 56.0 +/- 19.9 pg/mL)
and higher phosphorus (4.34 +/- 0.71 mg/dL vs 3.55 +/- 0.50 mg/dL) (P < 0.01).
Groups had similar levels of serum and urine calcium and 25-hydroxy- and 1,25
dihydroxy-vitamin D. The ACM group had higher bone turnover markers than control;
P1NP and CTX were strongly correlated (r2 = 0.82, P < 0.05). CTX was dependent on
age and disease group but not on sex or gonadal status. After treatment of
acromegaly, serum calcium (9.52 +/- 0.43 mg/dL to 9.26 +/- 0.28 mg/dL),
phosphorus (4.34 +/- 0.71 mg/dL to 3.90 +/- 0.80 mg/dL), and CTX (0.91 +/- 0.75
ng/mL to 0.63 +/- 0.68 ng/mL) decreased, while PTH increased (36.3 +/- 13.9 pg/mL
to 48.9 +/- 16.7 pg/mL) (P < 0.01). 25-hydroxy-vitamin D, P1NP, and RANK-L/OPG
ratio did not change significantly. Conclusion: Acromegaly patients exhibited PTH
independent calcium-phosphate alterations and enhanced coupled bone formation and
resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK
L/OPG changes were inconsistent.
PMID- 28407139
TI - Economic impact of remote monitoring after implantable defibrillators
implantation in heart failure patients: an analysis from the EFFECT study.
AB - Aims: Heart failure (HF) patients with implantable cardioverter-defibrillators
(ICD) require admissions for disease management and out-patient visits for
disease management and assessment of device performance. These admissions place a
significant burden on the National Health Service. Remote monitoring (RM) is an
effective alternative to frequent hospital visits. The EFFECT study was a
multicentre observational investigation aiming to evaluate the clinical
effectiveness of RM compared with in-office visits standard management (SM). The
present analysis is an economic evaluation of the results of the EFFECT trial.
Methods and results: The present analysis considered the direct consumption of
healthcare resources over 12-month follow-up. Standard tariffs were applied to
hospitalizations, in-office visits and remote device interrogations. Economic
comparisons were also carried out by means of propensity score (PS) analysis to
take into account the lack of randomization in the study design. The analysis
involved 858 patients with ICD or CRT-D. Of these, 401 (47%) were followed up via
an SM approach, while 457 (53%) were assigned to RM. The rate of hospitalizations
was 0.27/year in the SM group and 0.16/year in the RM group (risk reduction
=0.59; P = 0.0004). In the non-adjusted analysis, the annual cost for each
patient was ?817 in the SM group and ?604 in the RM group (P = 0.014). Propensity
score analysis, in which 292 RM patients were matched with 292 SM patients,
confirmed the results of the non-adjusted analysis (?872 in the SM group vs. ?757
in the RM group; P < 0.0001). Conclusion: There is a reduction in direct
healthcare costs of RM for HF patients with ICDs, particularly CRT-D, compared
with standard monitoring. Clinical Trial Registration:
http://clinicaltrials.gov/Identifier, NCT01723865.
PMID- 28407140
TI - Development and testing of candidate items for inclusion in a new rheumatoid
arthritis stiffness patient-reported outcome measure.
AB - Objective: To qualitatively develop and test a set of candidate items for a new
RA stiffness patient-reported outcome measure (PROM) that capture the patient
perspective. This is an essential first step in PROM development, prior to
quantitative development, assessment and validation. Methods: Focus groups
further examined the previously developed stiffness conceptual model and explored
the patient perspective regarding stiffness assessment. Data were analysed using
thematic analysis. An iterative process of item development was then performed by
the expert study team of researchers, patients and clinicians, based on the two
qualitative datasets and informed by measurement theory and guidelines. Finally,
these candidate items were tested using formal cognitive interview methodology
and subsequently refined. Results: Sixteen RA patients from the UK participated
in focus groups. Data confirmed the conceptual model of the RA patient experience
of stiffness and provided insight into stiffness assessment, including
suggestions regarding patient-relevant stiffness assessment categories such as
impact, location and timing. These data informed the development of 77 candidate
stiffness PROM items, including multiple formats for some. Eleven RA patients
participated in cognitive interviews. Minor changes were made to items to enhance
understanding and 32 items were removed, resulting in 45 candidate PROM items.
Conclusion: Rigorous qualitative methodology and considerable patient involvement
has underpinned items for a new RA stiffness PROM with strong content validity.
Crucially, patient involvement broadened assessment beyond early morning
stiffness duration, which may address existing PROM limitations. Items are now
suitable for quantitative item reduction, structural development of the final
PROM and validation.
PMID- 28407141
TI - Sensory Deprivation Triggers Synaptic and Intrinsic Plasticity in the
Hippocampus.
AB - Hippocampus, a temporal lobe structure involved in learning and memory, receives
information from all sensory modalities. Despite extensive research on the role
of sensory experience in cortical map plasticity, little is known about whether
and how sensory experience regulates functioning of the hippocampal circuits.
Here, we show that 9 +/- 2 days of whisker deprivation during early mouse
development depresses activity of CA3 pyramidal neurons by several principal
mechanisms: decrease in release probability, increase in the fraction of silent
synapses, and reduction in intrinsic excitability. As a result of deprivation
induced presynaptic inhibition, CA3-CA1 synaptic facilitation was augmented at
high frequencies, shifting filtering properties of synapses. The changes in the
AMPA-mediated synaptic transmission were accompanied by an increase in NR2B
containing NMDA receptors and a reduction in the AMPA/NMDA ratio. The observed
reconfiguration of the CA3-CA1 connections may represent a homeostatic adaptation
to augmentation in synaptic activity during the initial deprivation phase. In
adult mice, tactile disuse diminished intrinsic excitability without altering
synaptic facilitation. We suggest that sensory experience regulates computations
performed by the hippocampus by tuning its synaptic and intrinsic
characteristics.
PMID- 28407142
TI - Obinutuzumab induces superior B-cell cytotoxicity to rituximab in rheumatoid
arthritis and systemic lupus erythematosus patient samples.
AB - Objective: A proportion of RA and SLE patients treated with standard doses of
rituximab (RTX) display inefficient B cell deletion and poor clinical responses
that can be augmented by delivering higher doses, indicating that standard-dose
RTX is a sub-optimal therapy in these patients. This study aimed to investigate
whether better responses could be achieved with mechanistically different anti
CD20 mAbs. Methods: We compared RTX with obinutuzumab (OBZ), a new-generation,
glycoengineered type II anti-CD20 mAb, in a series of in vitro assays measuring B
cell cytotoxicity in RA and SLE patient samples. Results: We found that OBZ was
at least 2-fold more efficient than RTX at inducing B-cell cytotoxicity in in
vitro whole blood assays. Dissecting this difference, we found that RTX elicited
more potent complement-dependent cellular cytotoxicity than OBZ. In contrast, OBZ
was more effective at evoking Fc gamma receptor-mediated effector mechanisms,
including activation of NK cells and neutrophils, probably due to stronger
interaction with Fc gamma receptors and the ability of OBZ to remain at the cell
surface following CD20 engagement, whereas RTX became internalized. OBZ was also
more efficient at inducing direct cell death. This was true for all CD19 + B
cells as a whole and in naive (IgD + CD27 - ) and switched (IgD - CD27 + ) memory
B cells specifically, a higher frequency of which is associated with poor
clinical response after RTX. Conclusion: Taken together, these data provide a
mechanistic basis for resistance to rituximab-induced B-cell depletion, and for
considering obinutuzumab as an alternative B-cell depleting agent in RA and SLE.
PMID- 28407143
TI - Effect of Weather Variability on Seasonal Influenza Among Different Age Groups in
Queensland, Australia: A Bayesian Spatiotemporal Analysis.
AB - Background: The effects of weather variability on seasonal influenza among
different age groups remain unclear. The comparative study aims to explore the
differences in the associations between weather variability and seasonal
influenza, and growth rates of seasonal influenza epidemics among different age
groups in Queensland, Australia. Methods: Three Bayesian spatiotemporal
conditional autoregressive models were fitted at the postal area level to
quantify the relationships between seasonal influenza and monthly minimum
temperature (MIT), monthly vapor pressure, school calendar pattern, and Index of
Relative Socio-Economic Advantage and Disadvantage for 3 age groups (<15, 15-64,
and >=65 years). Results: The results showed that the expected decrease in
monthly influenza cases was 19.3% (95% credible interval [CI], 14.7%-23.4%),
16.3% (95% CI, 13.6%-19.0%), and 8.5% (95% CI, 1.5%-15.0%) for a 1 degrees C
increase in monthly MIT at <15, 15-64, and >=65 years of age, respectively, while
the average increase in the monthly influenza cases was 14.6% (95% CI, 9.0%
21.0%), 12.1% (95% CI, 8.8%-16.1%), and 9.2% (95% CI, 1.4%-16.9%) for a 1-hPa
increase in vapor pressure. Conclusions: Weather variability appears to be more
influential on seasonal influenza transmission in younger (0-14) age groups. The
growth rates of influenza at postal area level were relatively small for older
(>=65) age groups in Queensland, Australia.
PMID- 28407144
TI - The North American Primary Care Research Group's Patient and Clinician Engagement
Program (PaCE): Demystifying patient engagement through a dyad model.
AB - Background: Community engagement in research is essential for translating the
best evidence into community and clinical practice to improve the health and well
being of the population. Objective: North American Primary Care Research Group's
Patient and Clinician Engagement Program (PaCE) program aims to develop a robust
community of patients and primary care providers with knowledge and understanding
of the unique features of patient-centred outcomes research related to primary
care in order to advocate for and engage in research. Methods: PaCE employs a
'dyad' model in which a patient and a primary care provider collaborate to learn
about and engage in primary care, primary care research, grant review, proposal
development and advocacy. A series of educational trainings held in conjunction
with national primary care conferences, international webinars and local symposia
make up the foundation of the PaCE curriculum. Results and Conclusions: To date,
186 participants have completed the full-day, interactive PaCE training, and more
than 250 people have participated in PaCE webinars and/or symposia. A 6-month
follow-up sent to PaCE participants evaluates engagement activities following
training.
PMID- 28407145
TI - GEPIA: a web server for cancer and normal gene expression profiling and
interactive analyses.
AB - Tremendous amount of RNA sequencing data have been produced by large consortium
projects such as TCGA and GTEx, creating new opportunities for data mining and
deeper understanding of gene functions. While certain existing web servers are
valuable and widely used, many expression analysis functions needed by
experimental biologists are still not adequately addressed by these tools. We
introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based
tool to deliver fast and customizable functionalities based on TCGA and GTEx
data. GEPIA provides key interactive and customizable functions including
differential expression analysis, profiling plotting, correlation analysis,
patient survival analysis, similar gene detection and dimensionality reduction
analysis. The comprehensive expression analyses with simple clicking through
GEPIA greatly facilitate data mining in wide research areas, scientific
discussion and the therapeutic discovery process. GEPIA fills in the gap between
cancer genomics big data and the delivery of integrated information to end users,
thus helping unleash the value of the current data resources. GEPIA is available
at http://gepia.cancer-pku.cn/.
PMID- 28407146
TI - High rates of latent TB infection in contacts and the wider community in South
India.
AB - Background: We aimed to compare TB transmission rates between case and community
households in Vellore, South India. Methods: 359 household contacts (HHC) and 363
community contacts (CC) were assessed with tuberculin skin test (TST) and
QuantiFERON TB Gold In-Tube test (QFT) between August 2010 and September 2011.
Concordance test and multivariate risk factor assessment were conducted using
logistic regression adjusted for clustering. Results: Latent TB infection (LTBI)
positivity was similar between the two groups using both tests, with only
moderate concordance observed between QFT and TST. Children of HHC (<15 years)
were at a higher risk for LTBI (odds of 2.37 [1.15-4.89] and 3.02 [1.22-7.45] for
TST and QFT respectively). Among adults, both age in decades (odds of 1.33 [1.14
1.15] and 1.16 [1.02-1.32] for TST and QFT, respectively) and the interaction of
male gender, smoking and alcohol consumption (odds of 4.06 [1.38-11.93] and 2.59
[1.19-5.64] for TST and QFT, respectively), were associated with increased risk
of LTBI. Conclusions: This study provides estimates of TB infection rates
accounting for both community and household exposure that contribute to
understanding of TB transmission in this setting. We suggest that assessment of
risk factors for infection need increased examination as prophylactic treatment
of LTBI are being considered.
PMID- 28407147
TI - HaploMerger2: rebuilding both haploid sub-assemblies from high-heterozygosity
diploid genome assembly.
AB - Summary: De novo assembly is a difficult issue for heterozygous diploid genomes.
The advent of high-throughput short-read and long-read sequencing technologies
provides both new challenges and potential solutions to the issue. Here, we
present HaploMerger2 (HM2), an automated pipeline for rebuilding both haploid sub
assemblies from the polymorphic diploid genome assembly. It is designed to work
on pre-existing diploid assemblies, which are typically created by using de novo
assemblers. HM2 can process any diploid assemblies, but it is especially suitable
for diploid assemblies with high heterozygosity (>=3%), which can be difficult
for other tools. This pipeline also implements flexible and sensitive assembly
error detection, a hierarchical scaffolding procedure and a reliable gap-closing
method for haploid sub-assemblies. Using HM2, we demonstrate that two haploid sub
assemblies reconstructed from a real, highly-polymorphic diploid assembly show
greatly improved continuity. Availability and Implementation: Source code,
executables and the testing dataset are freely available at
https://github.com/mapleforest/HaploMerger2/releases/. Contact:
hshengf2@mail.sysu.edu.cn. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28407148
TI - Effects of closed-loop stimulation vs. DDD pacing on haemodynamic variations and
occurrence of syncope induced by head-up tilt test in older patients with
refractory cardioinhibitory vasovagal syncope: the Tilt test-Induced REsponse in
Closed-loop Stimulation multicentre, prospective, single blind, randomized study.
AB - Aims: Closed-loop stimulation (CLS) seemed promising in preventing the recurrence
of vasovagal syncope (VVS) in patients with a cardioinhibitory response to head
up tilt test (HUTT) compared with conventional pacing. We hypothesized that the
better results of this algorithm are due to its quick reaction in high-rate
pacing delivered in the early phase of vasovagal reflex, which increase the
cardiac output and the blood pressure preventing loss of consciousness. Methods
and results: This prospective, randomized, single-blind, multicentre study was
designed as an intra-patient comparison and enrolled 30 patients (age 62.2 +/-
13.5 years, males 60.0%) with cardioinhibitory VVS, carrying a dual-chamber
pacemaker incorporating CLS algorithm. Two HUTTs were performed one week apart:
one during DDD-CLS 60-130/min pacing and the other during DDD 60/min pacing;
patients were randomly and blindly assigned to two groups: in one the first HUTT
was performed in DDD-CLS (n = 15), in the other in DDD (n = 15). Occurrence of
syncope and haemodynamic variations induced by HUTT was recorded during the
tests. Compared with DDD, DDD-CLS significantly reduced the occurrence of syncope
induced by HUTT (30.0% vs. 76.7%; P < 0.001). In the patients who had syncope in
both DDD and DDD-CLS mode, DDD-CLS significantly delayed the onset of syncope
during HUTT (from 20.8 +/- 3.9 to 24.8 +/- 0.9 min; P = 0.032). The maximum fall
in systolic blood pressure recorded during HUTT was significantly lower in DDD
CLS compared with DDD (43.2 +/- 30.3 vs. 65.1 +/- 25.8 mmHg; P = 0.004).
Conclusion: In patients with cardioinhibitory VVS, CLS reduces the occurrence of
syncope induced by HUTT, compared with DDD pacing. When CLS is not able to abort
the vasovagal reflex, it seems to delay the onset of syncope.
PMID- 28407149
TI - Determination of the Biological Form of Human Cytomegalovirus DNA in the Plasma
of Solid-Organ Transplant Recipients.
AB - Background: Whether cytomegalovirus (CMV) DNA exists in plasma as virion
associated or free DNA is uncertain. Methods: An assay combining DNase I
digestion and CMV quantitative polymerase chain reaction (DNase-CMV-qPCR) was
developed to differentiate free naked DNA from virion DNA. One hundred three
frozen and 10 fresh CMV DNA-positive plasma samples from solid-organ transplant
recipients (SOTRs) were tested. Three sets of paired qPCR (P-qPCR) assays with
amplicons of variable length were used to study CMV DNA fragmentation in 20 SOTR
plasma samples, viral stocks (Towne, Merlin, AD169) and the first World Health
Organization (WHO) international standard (IS) for CMV DNA. Results: In all
plasma samples, 98.8%-100% of CMV DNA was free DNA; this was the only form in 93
of 103 (90.3%) frozen and all 10 fresh samples tested using DNase-CMV-qPCR. Low
levels of virion CMV DNA were found in 10 of 103 (9.7%) samples with higher total
DNA load. Cytomegalovirus DNA results were highly reproducible for 3 CMV virus
stocks and WHO IS (P > .80), tested by three sets of paired q-PCR. However, for
the 20 SOTR plasma samples, the smaller amplicon assay result was 2.6-fold, 3.4
fold, and 6.5-fold higher than the longer amplicion result (P < .001).
Conclusions: Cytomegalovirus DNA in SOTR plasma is almost exclusively free DNA,
highly fragmented, and not virion associated.
PMID- 28407150
TI - Dissociable patterns of brain activity for mentalizing about known others: a role
for attachment.
AB - The human brain tracks dynamic changes within the social environment, forming and
updating representations of individuals in our social milieu. This mechanism of
social navigation builds an increasingly complex map of persons with whom we are
familiar and form attachments to guide adaptive social behaviors. We examined the
neural representation of known others along a continuum of attachment using fMRI.
Heterosexual adults (N = 29, 16 females), in romantic relationships for more than
2 years, made trait judgments for a romantic partner, parent, close friend,
familiar acquaintance and self-during scanning. Multivariate analysis, partial
least squares, was used to identify whole-brain patterns of brain activation
associated with trait judgments of known others across a continuum of attachment.
Across conditions, trait judgments engaged the default network and lateral
prefrontal cortex. Judgments about oneself and a partner were associated with a
common activation pattern encompassing anterior and middle cingulate, posterior
superior temporal sulcus, as well as anterior insula. Parent and close friend
judgments engaged medial and anterior temporal lobe regions. These results
provide novel evidence that mentalizing about known familiar others results in
differential brain activity. We provide initial evidence that the representation
of adult attachment is a distinguishing feature of these differences.
PMID- 28407152
TI - Drugs to Treat Alzheimer's Disease.
PMID- 28407151
TI - #FightingNurseStereotypes Using Social Media.
PMID- 28407154
TI - Living with Parkinson's Disease: Staying Determined.
AB - Parkinson's disease is one of the most common chronically disabling disorders of
the nervous system. The disorder affects predominately older adults; only 4% of
individuals are diagnosed before age 50. Receiving a diagnosis of Parkinson's
disease can be overwhelming for someone who is active and feels healthy, but new
research shows that patients who take charge of their illness by adopting
healthful habits of mind and body can slow the development of the disease and
have a better quality of life. [Journal of Psychosocial Nursing and Mental Health
Services, 55(4), 15-18.].
PMID- 28407153
TI - Premenstrual Exacerbations: Achieving Stability All Month, Every Month.
AB - Premenstrual syndrome, premenstrual dysphoric disorder, or premenstrual
exacerbation of a psychiatric condition may disrupt 10 years of a woman's life
over the course of her reproductive lifespan. As health care practitioners,
nurses see women who experience these premenstrual symptom exacerbations in all
treatment settings. Premenstrual exacerbation of psychiatric illness is a common
phenomenon, and it is treatable; however, research is limited and evidence-based
guidelines for treatment are sparse. The current article offers insights and an
algorithm, extrapolated from the existing literature, into a lesser-known
treatment strategy, semi-intermittent dosing, which will provide symptom
stability all month, every month. [Journal of Psychosocial Nursing and Mental
Health Services, 55(4), 9-13.].
PMID- 28407155
TI - Benefits of Being a Healthy Perfectionist: Examining Profiles in Relation to
Nurses' Well-Being.
AB - The aim of the current study was to examine perfectionism in relation to burn-out
and depressive symptoms in nurses. The sample comprised 581 nurses from various
medical units in several regional hospitals in Taiwan. The Center for
Epidemiologic Studies Depression Scale, Maslach Burnout Inventory-Human Service
Survey, and Almost Perfect Scale-Revised were used to assess depressive symptoms,
burnout, and perfectionism. Response data were analyzed through descriptive
statistics, Pearson's product-moment correlation, cluster analysis, and one-way
analysis of variance. Results showed that nurses in the healthy and unhealthy
perfectionist groups reported higher personal standards and organization than
nonperfectionists. In addition, the unhealthy and nonperfectionist groups
reported higher levels of perceived personal failure than healthy perfectionists.
The findings can be used to design psychoeducational programs that promote
nurses' self-awareness of cognitive style in understanding perfectionism and to
enhance mental health promotion at work. [Journal of Psychosocial Nursing and
Mental Health Services, 55(4), 22-28.].
PMID- 28407156
TI - Enhancing Care Models to Capture Psychological Trauma.
AB - Toxic levels of stress in childhood are an ongoing threat to public health.
Traumatized children have special needs for health care to address their
developmental, mental health, and medical problems, and mitigate risk for long
term health problems. Developmental trauma leads to increased use of medical,
social, correctional, and mental health services. Longitudinal and retrospective
studies link childhood trauma and adversity to academic difficulties, poor
health, and low economic productivity in adulthood. Studies demonstrate a clear
link among early childhood trauma, neglect, and malnutrition with somatic disease
processes, such as high blood pressure, coronary heart disease, and diabetes. A
wide range of care providers, from the emergency department to subspecialties,
should consider enhancing their typical models of care to include the special
needs of traumatized children and the adults they become. [Journal of
Psychosocial Nursing and Mental Health Services, 55(4), 29-36.].
PMID- 28407159
TI - "Crane Park, Kalamazoo" by Jonathan Wijnberg.
PMID- 28407157
TI - Consumers of Mental Health Services: Their Knowledge, Attitudes, and Practices
About High Energy Drinks and Drugs.
AB - To date, whether individuals with mental illness use high energy drinks (HED) to
offset their symptoms, or whether their use began after diagnosis or psychoactive
drugs were prescribed is unknown. Their degree of knowledge regarding their
symptoms, diagnosis, or what strategies they have used to feel better is also
undetermined. A search of the literature yielded no studies about these areas or
domains. The current article provides background information on caffeine and HED,
with or without alcohol, and the use patterns of consumers of mental health
services, as well as their attitudes and knowledge. Participants in the Network
for Psychiatric Nursing Researchers, who were consumers, influenced the current
study group to expand their thinking about how to address the unknown areas.
Their related work and publication are described. [Journal of Psychosocial
Nursing and Mental Health Services, 55(4), 37-43.].
PMID- 28407160
TI - Standard for Reporting Refractive Outcomes of Intraocular Lens-Based Refractive
Surgery.
PMID- 28407161
TI - Preliminary Evidence of Successful Near Vision Enhancement With a New Technique:
PrEsbyopic Allogenic Refractive Lenticule (PEARL) Corneal Inlay Using a SMILE
Lenticule.
AB - PURPOSE: To describe a new technique (PrEsbyopic Allogenic Refractive Lenticule
[PEARL] inlay) using an allogenic corneal inlay prepared from a small incision
lenticule extraction (SMILE) lenticule. METHODS: A SMILE lenticule of specified
thickness (mean: 61.5 +/- 3.32 um) was trephined at the center to 1-mm diameter
and implanted in the cornea on the coaxially sighted light reflex under a
femtosecond laser-created cap of 120 um in the nondominant eye of presbyopic
patients. RESULTS: Four emmetropic presbyopic patients underwent PEARL inlay
implantation in the nondominant eye. In the operated eye, uncorrected near visual
acuity at 33 cm improved from J8 to J2 in one and from J5, J6, and J7,
respectively, to J2 in three operated eyes with improvement between three and
five lines in all eyes. Uncorrected intermediate visual acuity ranged between J3
and J5 at 67 cm and uncorrected distance visual acuity remained 20/20 in the
operated eye and binocularly. The patients were comfortable and reported
independence from glasses for near, intermediate, and distance for all of their
routine visual tasks for the 6-month follow-up period. There were no complaints
of dysphotopsia or troublesome night glare/halos. All lenticules remained well
centered during the follow-up and no lenticule-induced complications were seen.
All patients reported satisfaction with the surgical procedure. Topography showed
a central area of prolateness corresponding to the PEARL inlay. The inlay was not
visible on naked eye examination. CONCLUSIONS: This preliminary study
demonstrates the safety and efficacy of a PEARL corneal inlay for presbyopic
correction. Further studies are recommended to determine long-term outcomes. [J
Refract Surg. 2017;33(4):224-229.].
PMID- 28407162
TI - Effects of Short-term Preoperative Topical Ketorolac on Pupil Diameter in Eyes
Undergoing Femtosecond Laser-Assisted Capsulotomy.
AB - PURPOSE: To assess pupil diameter before and after femtosecond laser-assisted
capsulotomy in patients who were pretreated with a short-term topical
nonsteroidal anti-inflammatory drug (NSAID) (ketorolac) versus those without
pretreatment. METHODS: This prospective, randomized, observational case series
included consecutive patients scheduled to undergo cataract extraction using the
Catalys femtosecond laser platform (Abbott Medical Optics, Inc., Santa Ana, CA)
to perform only capsulotomies. The same protocol for preoperative medical
mydriasis was used for all patients, whereas pupil diameter was assessed using a
surgical ruler immediately before and 3 minutes after femtosecond laser-assisted
capsulotomy. The patients were divided into two groups: one received short-term
topical ketorolac preoperatively and the other did not receive NSAID pretreatment
(control). RESULTS: A total of 42 eyes of 42 patients (1 eye per patient) were
included in the study. Mean pupillary miosis was 0.79 +/- 1.08 and 1.57 +/- 1.19
mm for the ketorolac and control groups, respectively. There was a statistically
significant decrease in pupil diameter for both groups individually (P < .05).
There was also a statistically significant difference between the two groups (P <
.05) with the induced miosis in the eyes that did not receive topical NSAIDs
prior to cataract extraction being twofold greater when compared with the miosis
of the eyes that received ketorolac pretreatment. CONCLUSIONS: Short-term topical
use of ketorolac prior to femtosecond laser-assisted cataract surgery seems to
induce significantly less pupillary miosis in comparison to eyes that did not
receive NSAID pretreatment. NSAID use is advised prior to femtosecond laser
assisted cataract surgery to minimize pupil miosis-related surgical difficulties
or complications during cataract extraction. [J Refract Surg. 2017;33(4):230
234.].
PMID- 28407163
TI - Effect of Topical Nonsteroidal Anti-inflammatory Drugs on Pupillary Size During
Uncomplicated Cataract Surgery.
AB - PURPOSE: To compare the effectiveness of three different topical nonsteroidal
anti-inflammatory drugs (NSAIDs) in inhibiting surgically induced miosis during
uncomplicated cataract phacoemulsification. METHODS: Prospective, randomized,
double-masked comparative study of patients aged 40 years or older with grades II
to III cataracts (Lens Opacities Classification System) and no other
comorbidities. Participants were randomized into four groups: 0.1% nepafenac,
0.03% flurbiprofen, 0.4% ketorolac, or lubricant (control group). Medications
were applied three times, starting 90 minutes before surgery at 30-minute
intervals. Phacoemulsification was performed by the same surgeon using the stop
and-chop technique. Pupillary area and vertical and horizontal pupil diameters
were measured at five surgical stages and analyzed with a computerized image
system. Multiple comparison tests were performed to analyze intergroup
differences. A P value of less than .05 was considered statistically significant.
RESULTS: A total of 88 eyes were included in the study (22 eyes per group).
Maximum pupillary area at the end of surgery was observed in the nepafenac group
(62.72 +/- 9.75 mm2) versus the ketorolac, flurbiprofen, and control groups (P =
.003, P =.001, and P < .001, respectively). The percentage of pupillary area loss
at the end of surgery was 7.50% with nepafenac, 9.84% with flurbiprofen, 10.09%
with ketorolac, and 13.83% with control. A trend to larger pupillary area and
diameters was found in the nepafenac, flurbiprofen, and ketorolac groups compared
with the control group, with better performance in maintaining larger pupil
diameters and area in the nepafenac group at all surgical stages. CONCLUSIONS:
All NSAIDs were effective in maintaining intraoperative mydriasis during
uncomplicated cataract phacoemulsification compared to the control group. [J
Refract Surg. 2017;33(4):236-242.].
PMID- 28407164
TI - Intraocular Pressure After Implantation of a Phakic Collamer Intraocular Lens
With a Central Hole.
AB - PURPOSE: To investigate the middle-term intraocular pressure (IOP) results after
implantation of a posterior chamber collagen copolymer phakic intraocular lens
(IOL) (V4c Visian; STAAR Surgical Co., Nidau, Switzerland) with a central hole in
patients with myopia. METHODS: This retrospective study enrolled patients who had
implantation of a phakic IOL with a central hole. IOP, central vault, and adverse
events were evaluated 1, 3, 6, 12, and 24 months postoperatively. RESULTS: The
study enrolled 763 eyes (384 patients, 128 men and 256 women). Mean follow-up was
7.0 +/- 7.2 months (range: 1 to 24 months). The mean IOP was 13.2 +/- 2.1 mm Hg
preoperatively. Postoperatively, the mean IOP was 12.4 +/- 1.7 mm Hg at 1 month,
12.5 +/- 1.8 mm Hg at 3 months, 12.6 +/- 1.3 mm Hg at 6 months, 12.6 +/- 1.4 mm
Hg at 12 months, and 12.7 +/- 1.1 mm Hg at 24 months. Only one case (0.13%)
presented an increased IOP (> 21 mm Hg) during the observation period. No
pupillary block or acute angle closure was recorded. IOP at the final follow-up
visit was 12.8 +/- 1.3 mm Hg. CONCLUSIONS: Implantation of central hole phakic
IOL in myopic patients provided good and safe IOP outcomes throughout the 24
month observation period. [J Refract Surg. 2017;33(4):244-249.].
PMID- 28407165
TI - Comparison of Corneal Epithelial Remodeling After Femtosecond Laser-Assisted
LASIK and Small Incision Lenticule Extraction (SMILE).
AB - PURPOSE: To comparatively investigate changes in epithelial thickness between
myopic femtosecond laser-assisted LASIK (FS-LASIK) and small incision lenticule
extraction (SMILE). METHODS: This study compared the topographic epithelial
thickness changes in 175 myopic eyes undergoing FS-LASIK (62 eyes) or SMILE (113
eyes). Epithelial thickness was obtained using spectral-domain optical coherence
tomography before surgery and 1 and 3 months after surgery. Topographic
epithelial thickness obtained by automatic algorithm and thickness variability
(standard deviation over 17 imaged areas) was compared between two groups.
Postoperative epithelial thickness changes were correlated with treatment
parameters. RESULTS: For FS-LASIK, the mean epithelial thickness of the center
zone (2 mm in diameter), paracenter (2 to 5 mm), and mid-periphery (5 to 6 mm)
increased by 3.4, 4.3, and 2.1 um, respectively, at 1 month and by 4.4, 5.1, and
2.9 um, respectively, at 3 months. There was an increase of 2.5, 3.9, and 4.5 um,
respectively, at 1 month and 3.0, 4.2, and 4.9 um, respectively, at 3 months
following SMILE. The epithelial thickness did not change between 1 and 3 months
postoperatively following SMILE, whereas it increased further after FS-LASIK. A
larger increase of epithelial thickness was observed in the central zone at 3
months following FS-LASIK than SMILE, whereas the opposite was observed in the
mid-periphery. The topographic thickness variability was greater after FS-LASIK
than SMILE. Corneal epithelial thickening was proportional to the amount of
myopia correction after both procedures. CONCLUSIONS: Topographic epithelial
remodeling patterns differ following FS-LASIK or SMILE. Epithelial remodeling
appears to stabilize more rapidly following SMILE than FS-LASIK. [J Refract Surg.
2017;33(4):250-256.].
PMID- 28407166
TI - Evaluation of the True Wavefront Aberrations in Eyes Implanted With a
Rotationally Asymmetric Multifocal Intraocular Lens.
AB - PURPOSE: Standard evaluation of aberrations from wavefront slope measurements in
patients implanted with a rotationally asymmetric multifocal intraocular lens
(IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), results in large
magnitude primary vertical coma, which is attributed to the intrinsic IOL design.
The new proposed method analyzes aberrometry data, allowing disentangling the IOL
power pupillary distribution from the true higher order aberrations of the eye.
METHODS: The new method of wavefront reconstruction uses retinal spots obtained
at both the near and far foci. The method was tested using ray tracing optical
simulations in a computer eye model virtually implanted with the Lentis Mplus
IOL, with a generic cornea or with anterior segment geometry obtained from custom
quantitative spectral-domain optical coherence tomography in a real patient. The
method was applied to laser ray tracing aberrometry data at near and far fixation
obtained in a patient implanted with the Lentis Mplus IOL. RESULTS: Higher order
aberrations evaluated from simulated and real retinal spot diagrams following the
new reconstruction approach matched the nominal aberrations (approximately 98%).
Previously reported primary vertical coma in patients implanted with this IOL
lost significance with the application of the proposed reconstruction.
CONCLUSIONS: Custom analysis of ray tracing-based retinal spot diagrams allowed
decoupling of the true higher order aberrations of the patient's eye from the
power pupillary distribution of a rotationally asymmetric multifocal IOL,
therefore providing the appropriate phase map to accurately evaluate through
focus optical quality. [J Refract Surg. 2017;33(4):257-265.].
PMID- 28407167
TI - Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff
Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.
AB - PURPOSE: To investigate two new stiffness parameters and their relationships with
the dynamic corneal response (DCR) parameters and compare normal and keratoconic
eyes. METHODS: Stiffness parameters are defined as Resultant Pressure at inward
applanation (A1) divided by corneal displacement. Stiffness parameter A1 uses
displacement between the undeformed cornea and A1 and stiffness parameter highest
concavity (HC) uses displacement from A1 to maximum deflection during HC. The
spatial and temporal profiles of the Corvis ST (Oculus Optikgerate, Wetzlar,
Germany) air puff were characterized using hot wire anemometry. An adjusted air
pressure impinging on the cornea at A1 (adjAP1) and an algorithm to
biomechanically correct intraocular pressure based on finite element modelling
(bIOP) were used for Resultant Pressure calculation (adjAP1 - bIOP). Linear
regression analyses between DCR parameters and stiffness parameters were
performed on a retrospective dataset of 180 keratoconic eyes and 482 normal eyes.
DCR parameters from a subset of 158 eyes of 158 patients in each group were
matched for bIOP and compared using t tests. A P value of less than .05 was
considered statistically significant. RESULTS: All DCR parameters evaluated
showed significant differences between normal and keratoconic eyes, except peak
distance. Keratoconic eyes had lower stiffness parameter values, thinner
pachymetry, shorter applanation lengths, greater absolute values of applanation
velocities, earlier A1 times and later second applanation times, greater HC
deformation amplitudes and HC deflection amplitudes, and lower HC radius of
concave curvature (greater concave curvature). Most DCR parameters showed a
significant relationship with both stiffness parameters in both groups.
CONCLUSIONS: Keratoconic eyes demonstrated less resistance to deformation than
normal eyes with similar IOP. The stiffness parameters may be useful in future
biomechanical studies as potential biomarkers. [J Refract Surg. 2017;33(4):266
273.].
PMID- 28407168
TI - Intraoperative Optical Coherence Tomography Vault Measurement in Posterior
Chamber Phakic Intraocular Lens Implantation.
AB - PURPOSE: To describe the use of intraoperative optical coherence tomography (OCT)
vault measurement in 5 cases of posterior chamber phakic intraocular lens (IOL)
implantation. METHODS: This case series included 5 eyes in 3 consecutive patients
undergoing phakic IOL implantation. RTVue OCT (Optovue, Inc., Fremont, CA) was
used to obtain intraoperative vault measurements after pupil constriction.
Visante OCT (Carl Zeiss Meditec, Jena, Germany) was used to obtain postoperative
vault measurements. RESULTS: Intraoperative vault measurements ranged from 228 to
1,060 um. There were no postoperative complications. Postoperative OCT vault
measurements ranged from 230 to 670 um. CONCLUSIONS: Intraoperative OCT can be a
useful tool in phakic IOL implantation to provide real-time intraoperative vault
measurements. This may help to confirm appropriate phakic IOL sizing and guide
decision-making at the time of surgery. [J Refract Surg. 2017;33(4):274-277.].
PMID- 28407169
TI - Collagen Cross-linking With Photoactivated Riboflavin (PACK-CXL) for Bacterial
Keratitis After Small Incision Lenticule Extraction (SMILE).
AB - PURPOSE: To report a case of infectious keratitis after small incision lenticule
extraction (SMILE) treated with collagen cross-linking with photoactivated
riboflavin (PACK-CXL). METHODS: Case report and literature review. RESULTS: A
patient presented with culture-proven bacterial keratitis 5 days after SMILE was
treated with fortified topical antibiotics and PACK-CXL. Irrigation of the
corneal cap-stromal bed interface, which can be difficult and affect visual
outcomes, was not performed. Clinical improvement was seen shortly after
treatment and resolution of keratitis was achieved at 2 weeks. CONCLUSIONS: This
is the first reported use of PACK-CXL in the management of infectious keratitis
after SMILE. PACK-CXL may help sterilize the infection and limit its spread
within the interface. [J Refract Surg. 2017;33(4):278-280.].
PMID- 28407170
TI - CXL at the Slit Lamp: No Clinically Relevant Changes in Corneal Riboflavin
Distribution During Upright UV Irradiation.
PMID- 28407171
TI - SMILE as Re-treatment for a Thick LASIK Flap.
PMID- 28407172
TI - Comparison of Combined Transepithelial Phototherapeutic Keratectomy and
Mechanical Debridement During Corneal Cross-linking.
PMID- 28407173
TI - Corrigendum to "The need for strategic development of safety sciences".
PMID- 28407174
TI - Opinion versus evidence for the need to move away from animal testing.
AB - Science is based on facts and their discourse. Willingly or unwillingly, facts
are mixed with opinion, i.e., views or judgments formed, not necessarily based on
fact or knowledge. This is often necessary, where we have controversial facts or
no definitive evidence yet, because we need to take decisions or have to
prioritize. Evidence-based approaches aim at identifying the facts and their
quality objectively and transparently; they are now increasingly embraced in
toxicology, especially by employing systematic reviews, meta-analyses, quality
scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology.
Such approaches aim at minimizing opinion, the "eminence-based" part of science.
Animal experiments are the basis of a lot of our textbook knowledge in the life
sciences, have helped to develop desperately needed therapies, and have made this
world a safer place. However, they represent only one of the many possible
approaches to accomplish all these things. Like all approaches, they come with
shortcomings, and their true contribution is often overrated. This article aims
to summarize their limitations and challenges beside the ethical and economical
concerns (i.e., costs and duration as well as costs following wrong decisions in
product development): they include reproducibility, inadequate reporting,
statistical under-powering, lack of inter-species predictivity, lack of
reflection of human diversity and of real-life exposure. Each and every one of
these increasingly discussed aspects of animal experiments can be amended, but
this would require enormous additional resources. Together, they prompt a need to
engineer a new paradigm to ensure the safety of patients and consumers, new
products and therapies.
PMID- 28407175
TI - OECD/EFSA workshop on developmental neurotoxicity (DNT): The use of non-animal
test methods for regulatory purposes.
PMID- 28407176
TI - Serum proteomic spectral characteristics of acute myeloid leukemia and their
clinical significance.
AB - We investigated the differences between the serum proteomic spectral
characteristics of acute myeloid leukemia (AML) patients and those of healthy
people. We collected peripheral blood serum samples from 62 AML patients and 15
healthy controls. After removing high-abundance proteins, low-abundance serum
proteins were separated using two-dimensional gel electrophoresis to identify
differences between AML patients and healthy people. We investigated the
different protein dots by mass fingerprint analysis, and evaluated the results
using the Masort retrieval program provided by the MSDB protein bank. To further
investigate the relationship between standard chemotherapy treatment efficacy and
differences in protein patterns, we divided 21 patients into two groups (A and B)
according to the efficacy of standard chemotherapy. Compared with the healthy
cases, the AML patients demonstrated significant abnormal expression in 14
proteins (P < 0.05); alpha1-trypsin inhibitor (P < 0.01), prealbumin (P < 0.01),
apolipoprotein E (P < 0.010), and apolipoprotein A-IV (P < 0.01) expression
decreased, whereas haptoglobin HP2 (P < 0.05), serum exogenous lectin (P < 0.05),
H factor homologue protein (P < 0.05), and serum amyloid A1 (P < 0.01) expression
increased. Further stratified analysis revealed that patients with high serum
lectin expression had poor outcomes. The study revealed various proteins with
differential expression levels in the peripheral blood of AML patients, and the
difference in serum lectin expression is related to the efficiency of standard
chemotherapy. Therefore, these proteins are potential diagnosis markers or
prognostic indicators of AML.
PMID- 28407177
TI - mRNA and protein expression levels of four candidate genes for ear size in
Erhualian and Large White pigs.
AB - Porcine ear size is an important characteristic for distinguishing among pig
breeds. In a previous genome-wide association study of porcine ear size, LEM
domain-containing 3 (LEMD3), methionine sulfoxide reductase B3 (MSRB3), high
mobility group AT-hook 2 (HMGA2), and Wnt inhibitory factor 1 (WIF1) were
implicated as important candidate genes for ear size. This study investigated the
expression levels of four candidate genes for ear size in Erhualian and Large
White pigs. Ten Erhualian pigs with large ears and eight Large White pigs with
small ears at 60 days of age were examined. The mRNA expression levels of the
four candidate genes were quantified by real-time polymerase chain reaction. WIF1
mRNA expression was significantly higher in Large White than in Erhualian pigs (P
< 0.05), whereas the expression levels of the other three genes were not
significantly different between the two breeds. The protein expression levels of
the four genes were analyzed using western blot. WIF1 protein expression was
significantly higher in Large White than in Erhualian pigs (P < 0.01), whereas
MSRB3 protein expression was significantly higher in Erhualian than in Large
White pigs (P < 0.05). There were no significant differences between the two
breeds in residual protein expression. These results suggest that WIF1 is the
main causal gene for ear size in pigs.
PMID- 28407178
TI - Phenotypic diversity of starch granules in cassava germplasm.
AB - Demand for the development of cassava varieties with different native starches
has guided the search for these characteristics in the germplasm of Manihot
esculenta Crantz. Therefore, the objective of this study was to estimate the
genetic diversity of cassava accessions for root and starch granule
characteristics to guide the future industrial application of this species.
Starches from 56 accessions were evaluated for the number of granules in 1 g of
starch (NTG), area (AG, MUm2), length (LG, MUm), width (WG, MUm), starch granule
roundness (Round), dry matter content in the roots (DMC, %), pulp color (PulCo),
and cyanogenic compounds (HCN). Images captured by light microscopy were used to
determine the average phenotypic values, and these were further analyzed by
principal component analysis (PCA) considering mixed data (quantitative and
qualitative). Significant differences between the cassava accessions for all
traits measured revealed wide variability in starch granule characteristics. Four
diversity groups with better fitness for the classification of cassava accessions
based on PulCo were identified, in comparison with HCN. Accessions with
differential starch characteristics were identified, and crossings for the
generation of segregating populations in order to obtain table and industry
varieties have been proposed.
PMID- 28407179
TI - Effect of gene transfection timing on TGF-beta1 expression in rabbit mandibular
distraction gap.
AB - Transforming growth factor-beta1 (TGF-beta1) is a member of the TGF-beta
superfamily, and plays an important role in promoting various stages of
intramembranous and endochondral bone formation. It is one of the major growth
factors that influence new bone formation in the distraction gap during
distraction osteogenesis (DO). The major problem of DO is the time required for
the treatment. Reports show that gene therapy accelerates osteogenesis, which can
significantly benefit patients with DO. However, the optimal timing of gene
transfection has not yet been reported. In this study, we used the New Zealand
rabbit mandibular DO model for transfecting recombinant plasmid pIRES-hVEGF165
hBMP2 during the latency, distraction, and consolidation periods of DO. The TGF
beta1 levels in the distraction gap were detected at different time-points by
immunohistochemistry and analyzed semi-quantitatively with the CMIAS-2001A
computerized image analyzer. The TGF-beta1 levels peaked after 7 days and
decreased after 14 days of consolidation in each group. In contrast, the TGF
beta1 levels in the transfected distraction period group were significantly
higher than those in the other groups. After 28 days of consolidation, TGF-beta1
levels decreased and there was no significant difference among the groups. These
results indicated that the genes transfected in the distraction period up
regulated the expression of TGF-beta1 more than in the latency and consolidation
periods, which promoted bone formation in the distraction gap through a series of
biological effects. Thus, we obtained a remarkable effect on new bone formation,
and showed that the distraction period is optimal for gene therapy.
PMID- 28407180
TI - Screening and identification of cucumber germplasm and rootstock resistance
against the root-knot nematode (Meloidogyne incognita).
AB - Root-knot nematodes (Meloidogyne spp) are destructive agricultural pests that
reduce the productivity of cultivated vegetables worldwide, especially when
vegetables are cropped continuously in greenhouses. Cucumbers (Cucumis sativus
L.), in particular, suffer extensive damage due to root-knot nematodes, and only
a few wild species are known to be resistant. Grafting of cultivated plants to
rootstocks of known resistant germplasms could be an effective method to resolve
this problem. In this study, 21 cucumber germplasms and seven rootstocks were
evaluated for resistance based on the growth of cucumber seedlings and resistance
indexes to Meloidogyne incognita, which were surveyed 25 days after inoculation
with M. incognita. Cluster analysis and principal component analysis (PCA) were
used to investigate the resistance of 21 cucumber germplasms and seven rootstocks
based on their growth and resistance indexes after inoculation with M. incognita.
These analyses showed that the 21 germplasms and seven rootstocks could be
divided into three groups based upon their resistance levels: moderately
resistant, susceptible, and highly susceptible to M. incognita. All 21 cucumber
germplasms exhibited susceptibility or high susceptibility to M. incognita and
most rootstocks exhibited moderate resistance. The PCA results were consistent
with those of the clustering analysis. The Jinyou No.1 cultivar had the highest
resistance to M. incognita among the 21 cucumber germplasms, and Huangzhen No.1
cultivar had the highest resistance among the seven rootstock cultivars.
PMID- 28407181
TI - In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells.
AB - Breast cancer adversely affects the health status of women; therefore, the
prevention and treatment of breast cancer is of critical importance. Lycopene is
known to possess several biological effects such as removal of free radicals,
alleviation of biological oxidative injury, and inhibition of tumor growth. In
this study, we aimed to illustrate the effect of lycopene on tumor cell
proliferation and modulation of cancer progression as well as its possible
underlying mechanisms in human breast carcinoma cell line MCF-7 in vitro. MCF-7
cells were treated with different lycopene concentrations for 24, 48, and 72 h.
Light field microscopy was used to observe cell morphology. MTT assay was used to
determine the effect of lycopene on MCF-7 proliferation. Flow cytometry was
employed to evaluate cell apoptosis. Real-time quantitative polymerase chain
reaction was performed to detect the expression of p53 and Bax. Under microscopic
examination, the untreated MCF-7 cells appeared to have a diamond or polygonal
shape. Lycopene treatment resulted in cell shrinkage and breakage, whose severity
increased in a dose and duration dependent manner. In addition, reduced cell
proliferation and increased apoptosis (P < 0.05) were observed using MTT assay
and flow cytometry, respectively. Moreover, lycopene could also upregulate the
expression of p53 and Bax mRNAs in MCF-7 cells. In conclusion, lycopene inhibits
proliferation and facilitates apoptosis of MCF-7 cells in vitro, possibly by
regulating the expression of p53 and Bax.
PMID- 28407182
TI - Genetic progress in sunflower crop in Rio Grande do Sul State, Brazil.
AB - The sunflower has adaptability to growing regions with different climatic and
soil characteristics, showing drought tolerance and high-quality oil production.
The State of Rio Grande do Sul is the third largest sunflower producer in Brazil,
with research related to the sunflower breeding initiated after the decade of
1950. The aim of this study was to evaluate the genetic progress for grain yield,
oil content, and oil yield of sunflower (Helianthus annuus L.) in the State of
Rio Grande do Sul. Data of grain yield, oil content, and oil yield obtained from
58 sunflower cultivar yield trials in 19 municipalities in Rio Grande do Sul
during the period from 2005 to 2014 were used. Genetic progress was studied
according to the methodology proposed by Vencovsky and data from sunflower
cultivar yield trials were used. Annual genetic progress of sunflower during the
period of 10 years (2005-2014) was 132.46 kg?ha-1?year-1 for grain yield,
0.17%/year for oil content, and 48.11 kg?ha-1?year-1 for oil yield. The sunflower
breeding programs in the State of Rio Grande do Sul were efficient for the traits
grain yield and oil yield and presented no efficiency for oil content.
PMID- 28407183
TI - Sample size for estimation of direct effects in path analysis of corn.
AB - The objective of this study was to assess the sample size required for estimating
the direct effects of explanatory variables on the grain yield of corn in the
combinations formed by three types of hybrids x two harvests x nine scenarios of
explanatory variables x two types of path analyses x four levels of accuracy. A
total of 6340 plants were evaluated (361, 373, and 416 plants from single-,
triple-, and double-cross hybrids in the 2008/2009 harvest, respectively, and
1777, 1693, and 1720 plants from single-, triple-, and double-cross hybrids in
the 2009/2010 harvest, respectively). Eleven explanatory variables were measured
in each plant: plant height, ear insertion height, ear weight, number of grain
rows per ear, ear length and diameter, cob weight and diameter, 100-grain mass,
number of grains per ear, grain length and, the main variable, grain yield. Thus,
nine scenarios were planned (scenarios 1, 2, 3, 4, 5, 6, 7, 8, and 9 with 0, 1,
2, 3, 4, 5, 6, 7, and 8 explanatory variables excluded, respectively) and two
types of path analyses conducted (traditional and ridge path analyses). The
sample size required for estimating the direct effect of each explanatory
variable on grain yield was assessed using resampling with replacement at four
accuracy levels [95% confidence interval ranges (95%CI) of 0.15, 0.25, 0.35, and
0.45]. The use of the ninth scenario of path analysis is recommended regardless
of hybrid and harvest given the smaller sample size required compared to the
previous scenarios. To estimate direct effects with the maximum 95%CI of 0.25, 10
to 530 plants are required depending on the type of hybrid, harvest, scenario,
type of path analyses, and explanatory variables. To estimate the direct effects
in the ninth scenario with a maximum 95%CI of 0.25, 120 plants suffice regardless
of the type of hybrid, harvest, or type of path analyses.
PMID- 28407184
TI - Industrial tomato lines: morphological properties and productivity.
AB - The tomato is the second most produced vegetable in the world, with significant
participation in the human diet. In addition, the production of tomatoes
generates jobs and family income. The availability of improved cultivars that
provide greater profitability to the producer and satisfactorily meets the needs
of the fresh fruit market and the processing industry becomes imperative due to
its importance. Therefore, this study aimed to characterize and select industrial
tomato lines in regard to fruit yield, number of leaf branches, and number of
flower racemes (NFR). The experiment was conducted in 2014 in the experimental
area of the Federal University of Goias (Universidade Federal de Goias). The
design was a randomized block design with four replicates and 25 genotypes. The
number of leaf branches (NB), NFR, and fruit productivity were evaluated. The
results were analyzed using analysis of variance and the means compared by the
Tukey test. A difference was observed (P <= 0.01) for all traits analyzed. The NB
and NFR were related, where more branches promoted an increase in NFR and thus
the productivity increases. In addition, a greater number of fruits implied in
smaller fruit size, and consequently lower fruit mass. The lowest number of fruit
per plant caused increased fruit size and mass. The lines CVR 1, CVR 3, CVR 4,
CVR 5, CVR 21, and CVR 22 were suitable for genetic enhancement of tomato and
provided the greatest productivity.
PMID- 28407185
TI - Canonical correlations between agronomic traits and seed physiological quality in
segregating soybean populations.
AB - The objective of this study was to evaluate the relationship between agronomic
traits and physiological traits of seeds in segregating soybean populations by
canonical correlation analysis. Seven populations and two commercial cultivars in
three generations were used: F3 plants and F4 seeds; F4 plants and F5 seeds, and
F4 seeds and plants. The following agronomic traits (group I) were evaluated:
number of days to maturity, plant height at maturity, insertion height of first
pod, number of pods, grain yield, and oil content. The physiological quality of
seeds (group II) was evaluated using germination, accelerated aging, emergence,
and emergence rate index tests. The results showed that agronomic traits and
physiological traits of seeds are not independent. Intergroup associations were
established by the first canonical pair for the generation of F3 plants and F4
seeds, especially between more productive plants with a larger pod number and
high oil content and seeds with a high germination percentage and emergence rate.
For the generation of F4 plants and F5 seeds, the first canonical pair indicated
an association between reduced maturity cycle, seeds with a high emergence
percentage and a high percentage of normal seedlings after accelerated aging.
According to the second canonical pair, more productive and taller plants were
associated with seed vigor. For the generation of F4 seeds and plants, the
associations established by the first canonical pair occurred between seed vigor
and more productive plants with high oil content and reduced maturity cycle, and
those established by the second canonical pair between seeds of high
physiological quality and tall plants.
PMID- 28407187
TI - Genetic variability and expression of agro-morphological traits among genotypes
of Coffea arabica being promoted by supplementary irrigation.
AB - The use of supplementary irrigation to sustain the plantation during moments of
severe water stress or moments of high water demand is becoming almost a norm to
keep sustainable crops, especially due to the climate changes and the high
frequency in which climate extremes are occurring lately. The objective of this
study was to evaluate the agronomic performance and expression of genetic
variability among genotypes of Coffea arabica L. cultivated in farming systems
with different levels of water supply, focusing on rainfed or supplementary
irrigated systems. The experiment was developed in competition field, testing 8
genotypes of C. arabica L. in rainfed or supplementary irrigated systems. The
growth and production were evaluated during 2 consecutive cycles (2014-2015 and
2015-2016). Among the growth gains, it was observed large gains in coffee yield,
but the magnitude of the gains varied among genotypes. For crop yield, for
example, Paraiso MG/H 419-1 presented 136% gain, while Oeiras MG-6851 was capable
of yielding as much more coffee in rainfed conditions than in irrigated system.
The expression of variability for some agronomic traits (such as coffee yield,
canopy size, growth rate, and number of new buds) may be intensified by the
supplementary water supply, which promotes gains in production and growth,
increases the magnitude of variation among genotypes and allows to identify
different patterns for selection, which may not be observed in the rainfed
systems.
PMID- 28407186
TI - Antimicrobial activity and chemical composition of Brunfelsia uniflora flower
oleoresin extracted by supercritical carbon dioxide.
AB - Brunfelsia genus is traditionally utilized in popular medicine due to its
antibacterial and antifungal properties to name but a few. However, studies on
the antimicrobial activity of Brunfelsia uniflora flower oleoresin have not been
found yet. This study aimed to evaluate the chemical composition and
antimicrobial activity of B. uniflora flower oleoresin obtained by supercritical
carbon dioxide. Oleoresin from the plant dried flowers was obtained by carbon
dioxide, and the chemical composition was analyzed by gas chromatographic-mass
spectrometry. The minimum inhibitory concentration (MIC), minimum bactericidal
concentration (MBC), and minimum fungicidal concentration (MFC) of this oleoresin
for seven bacteria and eight fungi were determined using 96-well microtiter
plates. The oleoresin MBC for Bacillus cereus, Enterobacter cloacae, Escherichia
coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enterica, and
Staphylococcus aureus ranged from 0.01 to 0.08 mg/mL, whereas the controls
streptomycin and ampicillin varied from 0.1 and 0.5 mg/mL. The oleoresin MFC for
Aspergillus fumigatus, Aspergillus niger, Aspergillus ochraceus, Aspergillus
versicolor, Penicillium funiculosum, Penicillium ochrochloron, Penicillium
verrucosum var. cyclopium, and Trichoderma viride varied from 0.01 to 0.08 mg/mL,
whereas the controls bifonazole and ketoconazole ranged from 0.2 to 3.5 mg/mL.
The oleoresin obtained by supercritical carbon dioxide presented bacteriostatic,
bactericidal, fungistatic, and fungicidal activities that were higher than the
positive controls streptomycin, ampicillin, bifonazole, and ketoconazole. The
high antimicrobial activity was related to the high content of (E, E)
geranyllinalool that composes 21.0% of the oleoresin and a possible synergic
action with fatty acid esters that made up 50.5% of the oleoresin. The oleoresin
antimicrobial activity against common multiresistant bacteria in severe
infectious processes as P. aeruginosa or against toxin-producing fungi such as P.
ochrochloron or fungi that are difficult to control such as T. viride suggests
the development of promising applications of this product in the food, farming,
livestock, and pharmaceutical industry.
PMID- 28407188
TI - Genetic diversity of yacon accessions using ISSR markers.
AB - Yacon cultivation has been intensified and the investigations of this crop have
increased at the scientific, agricultural, and social levels because the roots of
yacon show beneficial properties for human health, such as reducing cholesterol
and glucose blood levels. Since the investigations involving yacon are very
recent, there is little information available in terms of the genetic
characterization of the cultivated genotypes. In view of the lack of information
on the accessions cultivated in the State of Espirito Santo, Brazil, this
pioneering study aimed to characterize 60 accessions cultivated in the state
using ISSR yacon markers with emphasis on identifying the genetic diversity among
the materials. The 20 ISSR primers used produced a total of 82 fragments, 39.6%
of which presented polymorphism. The number of fragments per primer ranged from 1
to 10. The dissimilarity values ranged from 0 to 0.54 according to the Jaccard
coefficient. A dendrogram was generated in which the accessions were divided into
3 groups; group 1 contained 58 individuals and groups 2 and 3 had only one
individual in each group. The clustering of 58 accessions in a single group shows
the low diversity in the materials examined. This low diversity indicates that
new genotypes must be introduced in order to promote increased variability, which
would minimize the adverse effects caused by biotic and abiotic factors.
PMID- 28407189
TI - Molecular analysis of genetic diversity among vine accessions using DNA markers.
AB - Viticulture presents a number of economic and social advantages, such as
increasing employment levels and fixing the labor force in rural areas. With the
aim of initiating a program of genetic improvement in grapevine from the State
University of the state of Rio de Janeiro North Darcy Ribeiro, genetic diversity
between 40 genotypes (varieties, rootstock, and species of different subgenera)
was evaluated using Random amplified polymorphic DNA (RAPD) molecular markers. We
built a matrix of binary data, whereby the presence of a band was assigned as "1"
and the absence of a band was assigned as "0." The genetic distance was
calculated between pairs of genotypes based on the arithmetic complement from the
Jaccard Index. The results revealed the presence of considerable variability in
the collection. Analysis of the genetic dissimilarity matrix revealed that the
most dissimilar genotypes were Rupestris du Lot and Vitis rotundifolia because
they were the most genetically distant (0.5972). The most similar were genotypes
31 (unidentified) and Rupestris du lot, which showed zero distance, confirming
the results of field observations. A duplicate was confirmed, consistent with
field observations, and a short distance was found between the variety 'Italy'
and its mutation, 'Ruby'. The grouping methods used were somewhat concordant.
PMID- 28407190
TI - Selection of morphoagronomic descriptors for the characterization of accessions
of cassava of the Eastern Brazilian Amazon.
AB - The aim of this study was to select morphoagronomic descriptors to characterize
cassava accessions representative of Eastern Brazilian Amazonia. It was
characterized 262 accessions using 21 qualitative descriptors. The multiple
correspondence analysis (MCA) technique was applied using the criteria:
contribution of the descriptor in the last factorial axis of analysis in
successive cycles (SMCA); reverse order of the descriptor's contribution in the
last factorial axis of analysis with all descriptors ('O''p') of Jolliffe's
method; mean of the contribution orders of the descriptor in the first three
factorial axes in the analysis with all descriptors ('Os') together with
('O''p'); and order of contribution of weighted mean in the first three factorial
axes in the analysis of all descriptors ('Oz'). The dissimilarity coefficient was
measured by the method of multicategorical variables. The correlation among the
matrix generated with all descriptors and matrices based on each criteria varied
(r = 0.21, r = 0.97, r = 0.98, r = 0.13 for SMCA, 'Os', 'Oz' and 'O''p',
respectively). The least informative descriptors were discarded independently and
according to both 'Os' and 'Oz' criteria. Thirteen descriptors were capable to
discriminate the accessions and to represent the morphological variability of
accessions sampled in Brazilian Eastern Amazonia: color of apical leaves, petiole
color, color of stem exterior, external color of storage root, color of stem
cortex, color of root pulp, texture of root epidermis, color of leaf vein, color
of stem epidermis, color of end branches of adult plant, branching habit, root
shape, and constriction of root.
PMID- 28407191
TI - Genome-wide association analysis of body conformation traits in Mexican Holstein
cattle using a mix of sampled and imputed SNP genotypes.
AB - In arid and semi-arid zones, animal health and production are closely correlated
with body conformation traits. These selected traits, in turn, allow livestock to
adapt unfavorable soil and environmental conditions. The primary objective of
this study was to perform a genome-wide association analysis for a set of sampled
and imputed SNPs with 16 conformation traits in a population of Holstein cows
from a desert area of Northwestern Mexico. Imputation from 6K to 50K SNPs was
performed as a low-cost optimization strategy. Results show eight SNPs associated
with two conformation traits. The Udder Depth trait resulted in seven associated
SNPs from chromosome 10, that related to Marbling Score, Milk Yield, Fat Yield,
Protein Yield, and Protein Percentage Quantitative Trait Loci (QTLs). The Body
Depth trait resulted in one associated SNP from chromosome 2, although no QTL
relation was found. The discovery of genes associated with conformation traits
may be indicative of the adaptive selection pressures the Holstein breed has
undergone in response to the extreme weather conditions found in the northwestern
areas of Mexico. Results of this study indicate that traits such as stature and
body depth may be used as indicators of cows' potential genetic merits for milk,
fat, and protein production.
PMID- 28407192
TI - Population genetic characterization of the Japanese oak silkmoth, Antheraea
yamamai (Lepidoptera: Saturniidae), using novel microsatellite markers and
mitochondrial DNA gene sequences.
AB - The Japanese oak silkmoth, Antheraea yamamai Guerin-Meneville, 1861 (Lepidoptera:
Saturniidae), is an important natural resource of industrial value for silk fiber
production. Owing to a lack of geographic and population genetic information,
systematic domestication of An. yamamai has not been possible yet. In this study,
10 microsatellite markers developed using next-generation sequencing and two
mitochondrial DNA (mtDNA) gene sequences (COI and ND4) were used to investigate
the genetic variation and geographic structure of An. yamamai populations in
South Korea. The two mtDNA gene sequences revealed very low total genetic
variation and, consequently, low geographic variation, validating the use of more
variable molecular markers. Genotyping of 76 An. yamamai individuals from nine
localities in South Korea showed that the observed number of alleles at each
locus ranged from 3 to 26, the polymorphism information content was 0.2990
0.9014, the observed and expected heterozygosities were 0.3252-0.9076 and 0.2500
0.9054, respectively, and FIS was -0.654-0.520. The population-based FIS, FST,
RST, and global Mantel tests all suggested that the An. yamamai populations were
overall well-interconnected, suggesting that any population can be used as a
genetic source for domestication. Nevertheless, STRUCTURE analyses using
microsatellite data and mtDNA sequences indicated the presence of two genetic
pools in many populations, although a plausible explanation for this observation
requires further studies.
PMID- 28407193
TI - A rapid and high-quality method for total RNA isolation from Haematococcus
pluvialis.
AB - Haematococcus pluvialis, as the most potential natural source of astaxanthin,
which is a powerful antioxidant with high economic value, has attracted more and
more scientific attention in recent years. An in-depth understanding of the
mechanism for how H. pluvialis produces astaxanthin requires the intensive
investigations on its genetic information. In particular, many reported studies
were based on a variety of RNA analyses. However, it is difficult to extract RNA
with high quality and quantity from H. pluvialis, because of the blockage from
its thick cell wall and contamination by a large quantity of pigments,
polysaccharides, and lipids. Therefore, we proposed an optimized Trizol-based RNA
extraction method for H. pluvialis by investigating the effect of cell wall
broken ways, algal strains, and cell growth status on total RNA isolation. Using
this rapid, convenient, and cost-saving method, isolated H. pluvialis RNA had
high quantity and quality (with an RNA integrity number of 7.0 and a
concentration of 1604.1 ng/MUL) equivalent to that isolated by commercial kit,
enabling its applications into downstream RNA analyses.
PMID- 28407195
TI - Development of TRAP primers for Ricinus communis L.
AB - The objective of this article was to develop TRAP (target region amplification
polymorphism) primers for castor bean, with the goal of making functional markers
available for genetic studies about the species. To do this, oligonucleotides
were designed based on ESTs, obtained from the NCBI (National Center for
Biotechnology Information) databank, which code enzymes involved in metabolic
routes of fatty acid synthesis, ricin synthesis, and resistance to castor bean
pathogens. The forward primers were designed with the help of the Primer3
software and, for the reverse, six arbitrary primers were used. To standardize
the amplification reactions, the following criteria were used to select the
primers: sizes between 18 and 20 bp, guanine/cytosine (GC) in the range of 40 to
60%, and average annealing temperature between 55 degrees and 62 degrees C. The
design quality of the primers was verified using the Net Primer application.
Fifty-six primers were designed, which had an average GC percentage of 53.2%. A
total of 336 combinations were obtained using the 56 fixed and 6 arbitrary
primers. Based on polymerase chain reaction, 330 combinations (89%) presented
good amplification patterns for the genomic DNA of castor bean. The size of the
fragments amplified varied between 50 and 2072 bp. The TRAP primers designed and
validated in this study are the first for castor bean and represent a significant
increase in the molecular markers for this species.
PMID- 28407194
TI - Genetic diversity among cotton cultivars in two environments in the State of Mato
Grosso.
AB - Using commercial cultivars to compose crossing blocks in cotton is a promising
strategy, because these materials have desirable agronomic and technological
characteristics. The objective of this study was to evaluate the genetic
diversity among 16 cotton cultivars cultivated in two environments in the State
of Mato Grosso, the largest national producer, using agronomical and
technological traits. There was significant effect to cultivars for all traits,
while genotype x environment interaction was significant only for average boll
weight, short fiber index, and maturity of fibers. Therefore, because of the
presence of genotype x environment interaction for three traits, we chose to
study genetic diversity among cotton cultivars separately in each environment and
investigate the interaction impact on the diversity among genotype pairs. Based
on agronomical and technological performance and genetic diversity among
cultivars in both environments, the most promising cross involves FM 910 and LD
CV 02. We also observed that lint percentage and average boll weight presented a
higher discrimination capacity in both environments.
PMID- 28407196
TI - Biotools: an R function to predict spatial gene diversity via an individual-based
approach.
AB - The gene diversity or expected heterozygosity (HE) is based on the allele
frequency and is often used as a measure of genetic variability of populations.
Knowing the pattern of spatial distribution of HE can be useful for determining
strategies of conservation and sampling of collections of individuals. In
addition, it can allow one to detect genetic boundaries in a landscape. We
adapted a Wombling method based on assignment tests in a circular moving window
extensively sampled over the study area in order to estimate HE at points of a
prediction grid. The function sHe(), package biotools, is an easy-to-use and
flexible implementation in R language that accepts as input geographical and
genotyping data. The package biotools is distribution-free under the GPL-2/3
license and currently available from the Comprehensive R Archive Network (CRAN)
at . The R platform and all R dependencies are similarly available from CRAN.
PMID- 28407197
TI - Autologous hematopoietic stem cell transplantation following high-dose
chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas.
AB - BACKGROUND: Soft tissue sarcomas (STS) are a highly heterogeneous group of rare
malignant solid tumors. Nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise
all STS except rhabdomyosarcoma. In people with advanced local or metastatic
disease, autologous hematopoietic stem cell transplantation (HSCT) applied after
high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe
hematologic toxicity. The rationale for this update is to determine whether any
randomized controlled trials (RCTs) have been conducted and to clarify whether
HDCT followed by autologous HSCT has a survival advantage. OBJECTIVES: To assess
the efficacy and safety of high-dose chemotherapy (HDCT) followed by autologous
hematopoietic stem cell transplantation (HSCT) for all stages of
nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) in children and adults. SEARCH
METHODS: For this update, we revised the search strategy to improve the precision
and reduce the number of irrelevant hits. We searched the following electronic
databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue
8), PubMed from 2012 to 6 September 2016, and Embase from 2012 to 26 September
2016. We searched online trial registries and congress proceedings from 2012 to
26 September 2016. SELECTION CRITERIA: Terms representing STS and autologous HSCT
were required in the title or abstract. We restricted the study design to RCTs.
We included studies if at least 80% of participants had a diagnosis listed in any
version of the World Health Organization (WHO) classification and classified as
malignant. The search included children and adults with no age limits. DATA
COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by
Cochrane. The primary outcomes were overall survival and treatment-related
mortality. MAIN RESULTS: We identified 1549 records; 85 items from electronic
databases, 45 from study registries, and 1419 from congress proceedings. The
revised search strategy did not identify any additional RCTs. In the previous
version of the review, we identified one RCT comparing HDCT followed by
autologous HSCT versus standard-dose chemotherapy (SDCT). The trial randomized 87
participants who were considerably heterogeneous with respect to 19 different
tumor entities. The data from 83 participants were available for analysis.In the
single included trial, overall survival at three years was 32.7% in the HDCT arm
versus 49.4% in the SDCT arm and there was no difference between the treatment
groups (hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.70 to 2.29, P =
0.44; 1 study, 83 participants; high quality evidence). In a subgroup of
participants who had a complete response before HDCT, overall survival was higher
in both treatment groups and overall survival at three years was 42.8% in the
HDCT arm versus 83.9% in the SDCT arm and favored the SDCT group (HR 2.92, 95% CI
1.1 to 7.6, P = 0.028; 1 study, 39 participants).In the single included trial,
the authors reported one treatment-related leukemia death two years after HDCT.
They also evaluated severe adverse events WHO grade 3 to 4 in 22 participants in
the HDCT arm and in 51 participants in the SDCT arm. The authors reported 11
events concerning digestive-, infection-, pain-, or asthenia-related toxicity in
the HDCT arm and one event in the SDCT arm (moderate quality evidence). The
development of secondary neoplasia was not addressed. We judged the study to have
an overall unclear risk of bias as three of seven items had unclear and four
items had low risk of bias. For GRADE, we judged three items as high quality and
three items were not reported. AUTHORS' CONCLUSIONS: The limited data of a single
RCT with an unclear risk of bias and moderate to high quality evidence showed no
survival advantage for HDCT. If this treatment is offered it should only be given
after careful consideration on an individual person basis and possibly only as
part of a well-designed RCT.
PMID- 28407198
TI - Chlorpromazine dose for people with schizophrenia.
AB - BACKGROUND: The World Health Organization (WHO) Model Lists of Essential
Medicines lists chlorpromazine as one of its five medicines used in psychotic
disorders. OBJECTIVES: To determine chlorpromazine dose response and dose side
effect relationships for schizophrenia and schizophrenia-like psychoses. SEARCH
METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of
Trials (December 2008; 2 October 2014; 19 December 2016). SELECTION CRITERIA: All
relevant randomised controlled trials (RCTs) comparing low doses of
chlorpromazine (<= 400 mg/day), medium dose (401 mg/day to 800 mg/day) or higher
doses (> 800 mg/day) for people with schizophrenia, and which reported clinical
outcomes. DATA COLLECTION AND ANALYSIS: We included studies meeting review
criteria and providing useable data. Review authors extracted data independently.
For dichotomous data, we calculated fixed-effect risk ratios (RR) and their 95%
confidence intervals (CIs). For continuous data, we calculated mean differences
(MD) and their 95% CIs based on a fixed-effect model. We assessed risk of bias
for included studies and graded trial quality using GRADE (Grading of
Recommendations Assessment, Development and Evaluation). MAIN RESULTS: As a
result of searches undertaken in 2014, we found one new study and in 2016 more
data for already included studies. Five relevant studies with 1132 participants
(585 are relevant to this review) are now included. All are hospital-based trials
and, despite over 60 years of chlorpromazine use, have durations of less than six
months and all are at least at moderate risk of bias. We found only data on low
dose (<= 400 mg/day) versus medium-dose chlorpromazine (401 mg/day to 800 mg/day)
and low-dose versus high-dose chlorpromazine (> 800 mg/day).When low-dose
chlorpromazine (<= 400 mg/day) was compared to medium-dose chlorpromazine (401
mg/day to 800 mg/day), there was no clear benefit of one dose over the other for
both global and mental state outcomes (low-quality and very low-quality
evidence). There was also no clear evidence for people in one dosage group being
more likely to leave the study early, over the other dosage group (moderate
quality evidence). Similar numbers of participants from each group experienced
agitation and restlessness (very low-quality evidence). However, significantly
more people in the medium-dose group (401 mg/day to 800 mg/day) experienced
extrapyramidal symptoms in the short term (2 RCTS, n = 108, RR 0.47, 95% CI 0.30
to 0.74, moderate-quality evidence). No data for death were available.When low
dose chlorpromazine (<= 400 mg/day) was compared to high-dose chlorpromazine (>
800 mg/day), data from one study with 416 patients were available. Clear evidence
of a benefit of the high dose was found with regards to global state. The low
dose group had significantly fewer people improving (RR 1.13, 95% CI 1.01 to
1.25, moderate-quality evidence). There was also a marked difference between the
number of people leaving the study from each group for any reason, with
significantly more people leaving from the high-dose group (RR 0.60, 95% CI 0.40
to 0.89, moderate-quality evidence). More people in the low-dose group had to
leave the study due to deterioration in behaviour (RR 2.70, 95% CI 1.34 to 5.44,
low-quality evidence). There was clear evidence of a greater risk of people
experiencing extrapyramidal symptoms in general in the high-dose group (RR 0.43,
95% CI 0.32 to 0.59, moderate-quality evidence). One death was reported in the
high-dose group yet no effect was shown between the two dosage groups (RR 0.33,
95% CI 0.01 to 8.14, moderate-quality evidence). No data for mental state were
available. AUTHORS' CONCLUSIONS: The dosage of chlorpromazine has changed
drastically over the past 50 years with lower doses now being the preferred of
choice. However, this change was gradual and arose not due to trial-based
evidence, but due to clinical experience and consensus. Chlorpromazine is one of
the most widely used antipsychotic drugs yet appropriate use of lower levels has
come about after many years of trial and error with much higher doses. In the
absence of high-grade evaluative studies, clinicians have had no alternative but
to learn from experience. However, such an approach can lack scientific rigor and
does not allow for proper dissemination of information that would assist
clinicians find the optimum treatment dosage for their patients. In the future,
data for recently released medication should be available from high-quality
trials and studies to provide optimum treatment to patients in the shortest
amount of time.
PMID- 28407199
TI - Comprehensive Geriatric Assessment for Prevention of Delirium After Hip Fracture:
A Systematic Review of Randomized Controlled Trials.
AB - OBJECTIVES: To assess the efficacy of comprehensive geriatric assessment (CGA) in
prevention of delirium after hip fracture. DESIGN: Systematic review and
metaanalysis. SETTING: Ward based models on geriatrics wards and visiting team
based models on orthopaedics wards were included. PARTICIPANTS: Four trials
(three European, one U.S.; 973 participants) were identified. Two assessed ward
based, and two assessed team-based interventions. MEASUREMENTS: MEDLINE, EMBASE,
CINAHL and PsycINFO databases; Clinicaltrials.gov; and the Central Register of
Controlled Trials were searched. Reference lists from full-text articles were
reviewed. Incidence of delirium was the primary outcome. Length of stay, delirium
severity, institutionalization, long-term cognition and mortality were predefined
secondary outcomes. Duration of delirium was included as a post hoc outcome.
RESULTS: There was a significant reduction in delirium overall (relative risk
(RR) = 0.81, 95% confidence interval (CI) = 0.69-0.94) in the intervention group.
Post hoc subgroup analysis found this effect to be preserved in the team-based
intervention group (RR = 0.77, 95% CI = 0.61-0.98) but not the ward-based group.
No significant effect was observed on any secondary outcome. CONCLUSION: There
was a reduction in the incidence of delirium after hip fracture with CGA. This is
in keeping with results of non-randomized controlled trials and trials in other
populations. Team-based interventions appeared superior in contrast to the Ellis
CGA paper, but it is likely that heterogeneity in interventions and population
studied affected this.
PMID- 28407200
TI - Adrenomedullin 2/intermedin: a putative drug candidate for treatment of
cardiometabolic diseases.
AB - : Adrenomedullin (ADM) 2/intermedin (IMD) is a short peptide that belongs to the
CGRP superfamily. Although it shares receptors with CGRP, ADM and amylin, ADM2
has significant and unique functions in the cardiovascular system. In the past
decade, the cardiovascular effect of ADM2 has been carefully analysed. In this
review, progress in understanding the effects of ADM2 on the cardiovascular
system and its protective role in cardiometabolic diseases are summarized. LINKED
ARTICLES: This article is part of a themed section on Spotlight on Small
Molecules in Cardiovascular Diseases. To view the other articles in this section
visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
PMID- 28407201
TI - Cancer incidence profile in sub-Saharan African-born blacks in the United States:
Similarities and differences with US-born non-Hispanic blacks.
AB - BACKGROUND: Sub-Saharan African-born blacks (ABs) are one of the fastest-growing
populations in the United States. However, to the authors' knowledge, data
regarding the cancer burden in this group are lacking, which would inform
targeted cancer prevention and control. METHODS: The authors calculated age
standardized proportional incidence ratios (PIRs) comparing the frequency of the
top 15 cancers in ABs with that of US-born non-Hispanic blacks (USBs) by sex and
region of birth using incidence data for 2000 through 2012 from the Surveillance,
Epidemiology, and End Results (SEER 17) program. RESULTS: Compared with USBs, ABs
had significantly higher PIRs of infection-related cancers (liver, stomach, and
Kaposi sarcoma), blood cancers (leukemia and non-Hodgkin lymphoma), prostate
cancer, and thyroid cancers (females only). For example, the PIR for Kaposi
sarcoma in AB versus USB women was 12.06 (95% confidence interval [95% CI], 5.23
18.90). In contrast, ABs had lower PIRs for smoking-related and colorectal
cancers (eg, for lung cancer among men, the PIR was 0.30 [95% CI, 0.27-0.34]).
Furthermore, cancer occurrence in ABs versus USBs varied by region of birth. For
example, the higher PIRs for liver cancer noted among male ABs (PIR, 3.57; 95%
CI, 1.79-5.35) and for thyroid cancer in female ABs (PIR, 3.03; 95% CI, 2.03
4.02) were confined to Eastern African-born blacks, whereas the higher PIR for
prostate cancer (PIR, 1.90; 95% CI, 1.78, 2.02) was confined to Western African
born blacks. CONCLUSIONS: The cancer incidence profile of ABs is different from
that of USBs and varies by region of birth, suggesting differences in
environmental, cultural, social, and genetic factors. The findings of the current
study could stimulate etiologic research and help to inform targeted
interventions. Cancer 2017;123:3116-24. (c) 2017 American Cancer Society.
PMID- 28407202
TI - Altered white matter integrity in adults with autism spectrum disorder and an IQ
>100: a diffusion tensor imaging study.
AB - OBJECTIVE: White matter (WM) alterations have been reported in children and
adults with autism spectrum disorder (ASD). In particular, impaired connectivity
of limbic structures may be related to social deficits. Heterogeneous findings
could be explained in terms of differences in sample characteristics and
methodology. In this context, non-syndromic forms might differ substantially in
WM structure from secondary ASD forms. METHOD: In an attempt to recruit a
homogeneous study sample, we included adults with high-functioning ASD and an IQ
> 100 to decrease the influence of syndromic forms being often associated with
cognitive deficits. Diffusion tensor imaging (DTI) was performed in 30
participants with ASD and 30 pairwise-matched controls. Fractional anisotropy
(FA) and mean diffusivity (MD) as surrogate imaging markers for WM integrity were
calculated. RESULTS: We found a significant FA decrease in the ASD group in the
genu and body of the corpus callosum (CC). Increased MD was detected in the
subgenual anterior cingulate cortex (sACC). CONCLUSION: The finding of decreased
WM integrity in the genu of the CC is in line with earlier studies reporting a
decreased number of interhemispheric fibers in the frontal lobe of ASD.
Alterations in the sACC might be associated with 'Theory of mind' deficits.
PMID- 28407203
TI - On the multiple imputation variance estimator for control-based and delta
adjusted pattern mixture models.
AB - Control-based pattern mixture models (PMM) and delta-adjusted PMMs are commonly
used as sensitivity analyses in clinical trials with non-ignorable dropout. These
PMMs assume that the statistical behavior of outcomes varies by pattern in the
experimental arm in the imputation procedure, but the imputed data are typically
analyzed by a standard method such as the primary analysis model. In the multiple
imputation (MI) inference, Rubin's variance estimator is generally biased when
the imputation and analysis models are uncongenial. One objective of the article
is to quantify the bias of Rubin's variance estimator in the control-based and
delta-adjusted PMMs for longitudinal continuous outcomes. These PMMs assume the
same observed data distribution as the mixed effects model for repeated measures
(MMRM). We derive analytic expressions for the MI treatment effect estimator and
the associated Rubin's variance in these PMMs and MMRM as functions of the
maximum likelihood estimator from the MMRM analysis and the observed proportion
of subjects in each dropout pattern when the number of imputations is infinite.
The asymptotic bias is generally small or negligible in the delta-adjusted PMM,
but can be sizable in the control-based PMM. This indicates that the inference
based on Rubin's rule is approximately valid in the delta-adjusted PMM. A simple
variance estimator is proposed to ensure asymptotically valid MI inferences in
these PMMs, and compared with the bootstrap variance. The proposed method is
illustrated by the analysis of an antidepressant trial, and its performance is
further evaluated via a simulation study.
PMID- 28407204
TI - Nitric oxide and hydrogen sulfide: the gasotransmitter paradigm of the vascular
system.
AB - : There are several reviews on NO and hydrogen sulfide (H2 S) and their role in
vascular diseases in the current relevant literature. The aim of this review is
to discuss, within the limits of present knowledge, the interconnection between
these two gasotransmitters in vascular function. In particular, the review
focuses on the role played by the balance between the NO and H2 S pathways in
either physiological or pathological conditions. The distinction between
physiology and pathology has been made in order to dissect the molecular basis of
this crosstalk, highlighting how and if this balance varies, depending upon the
vascular status. Perspectives and possible novel therapeutic approaches are also
discussed. LINKED ARTICLES: This article is part of a themed section on Targeting
Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in
this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and
http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
PMID- 28407208
TI - Vitamin D for Healthy Aging.
PMID- 28407205
TI - Association Between Vascular Pathology and Rate of Cognitive Decline Independent
of Alzheimer's Disease Pathology.
AB - OBJECTIVES: To examine the association between vascular pathology and rate of
cognitive decline in older adults independent of Alzheimer's disease (AD)
pathology. DESIGN: Prospective cohort study. SETTING: Community sample.
PARTICIPANTS: Individuals from the Einstein Aging Study autopsy series (N = 62).
MEASUREMENTS: The Blessed Information-Memory-Concentration (BIMC) test was used
to assess global cognitive status. AD pathology was quantified according to Braak
stage (<3 vs >= 3). Vascular pathology was quantified using a previously reported
macrovascular lesion (MVL) score. The association between vascular pathology and
antemortem rates of cognitive decline adjusted for level of AD pathology was
assessed using linear mixed-effects models. RESULTS: Mean age was 81.8 at
enrollment and 89.0 at death. Participants with more than two MVLs had faster
cognitive decline than those with no MVLs (difference in annual rate of change in
BIMC 0.74 points/yr, P = .03). Braak stage was also associated with cognitive
decline (difference 0.57 points/yr, P = .03). The difference in rate of cognitive
decline between those with more than two MVLs and those free of vascular lesions
persisted after adjustment for AD pathology (difference in rate of change in BIMC
0.68 points/yr, P = .04). The effect of vascular pathology on cognitive decline
was not significantly different according to AD pathology. CONCLUSION: Vascular
brain pathology is associated with rate of cognitive decline after adjusting for
level of AD pathology.
PMID- 28407206
TI - Pre-ejection period reactivity to reward is associated with anhedonic symptoms of
depression among adolescents.
AB - Pre-ejection period (PEP) reactivity to reward has been posited as a specific
index of behavioral approach and incentive motivation, suggesting it might be
uniquely associated with the affective and motivational deficits of anhedonia.
This study evaluated PEP reactivity to a reward task as a predictor of depressive
symptoms among adolescents, examining global depressive symptoms as well as
specific anhedonic and nonanhedonic symptoms clusters. Participants included 76
adolescents, ages 11-15 years (52% female). This study found marginal support for
an association between PEP reactivity to reward and concurrent anhedonia
symptoms, but no association with nonanhedonic or the global scale. Findings are
discussed in terms of potential associations between peripheral
psychophysiological measures and dopaminergic functioning and also the utility of
this measure for future research on anhedonia.
PMID- 28407209
TI - Neutrophil-To-Lymphocyte Ratio: An Emerging Marker Predicting Prognosis in
Elderly Adults with Community-Acquired Pneumonia.
AB - OBJECTIVES: To explore the performance of the neutrophil-to-lymphocyte ratio
(NLR), an index of systemic inflammation that predicts prognosis of several
diseases, in a cohort of elderly adults with community-acquired pneumonia (CAP).
DESIGN: Prospective clinical study from January 2014 to July 2016. SETTING: Unit
of Internal Medicine, University of Catania, Catania, Italy. PARTICIPANTS:
Elderly adults admitted for CAP (N = 195). MEASUREMENTS: Clinical diagnosis of
CAP was defined as the presence of a new infiltrate on plain chest radiography or
chest computed tomography associated with one or more suggestive clinical
features such as dyspnea, hypo- or hyperthermia, cough, sputum production,
tachypnea (respiration rate >20 breaths per minute), altered breath sounds on
physical examination, hypoxemia (partial pressure of oxygen <60 mmHg),
leukocytosis (white blood cell count >10,000/MUL). Clinical examination,
traditional tests such as Pneumonia Severity Index (PSI); Confusion, Urea,
Respiratory rate, Blood pressure, aged 65 and older (CURB-65), and NLR were
evaluated at admission. The accuracy and predictive value for 30-day mortality of
traditional scores and NLR were compared. RESULTS: NLR predicted 30-day mortality
(P < .001) and performed better than PSI (P < .05), CURB-65, C-reactive protein,
and white blood cell count (P < .001) to predict prognosis. No deaths occurred in
participants with a NLR of less than 11.12. Thirty-day mortality was 30% in those
with a NLR between 11.12% and 13.4% and 50% in those with a NLR between 13.4 and
28.3. All participants with a NLR greater than 28.3 died within 30 days.
CONCLUSIONS: These results would encourage early discharge of individuals with a
NLR of less than 11.12, short-term in-hospital care for those with a NLR between
11.12 and 13.4, middle-term hospitalization for those with a NLR between 13.4 and
28.3, and admission to a respiratory intensive care unit for those with a NLR
greater than 28.3.
PMID- 28407210
TI - The association of sleep disturbances with endocrine and perceived stress
reactivity measures in male employees.
AB - Evidence on the relationship between stress reactivity and sleep is conflicting.
This study examined the association between disturbed sleep and perceived and
endocrine stress reactivity independently of age, body mass index (BMI), and
chronic stress. One hundred and twenty middle-aged men were exposed to the Trier
Social Stress Test for Groups. The Pittsburgh Sleep Quality Index and the
Perceived Stress Reactivity Scale were used to assess sleep and perceived stress
reactivity, respectively. Endocrine stress reactivity was examined by assessing
salivary cortisol levels. Regression analyses showed that men with disturbed
sleep had blunted overall cortisol responses (b = -18.246, p = .044), but the
association did not survive adjustment for age, BMI, and chronic stress. In
contrast, poor sleep was associated with heightened perceived stress reactivity
independently of age and BMI (b = 0.235, p = .005), but additional adjustment for
chronic stress attenuated the relationship and only chronic stress remained a
significant predictor of perceived stress reactivity (b = 0.470, p < .001).
Cortisol and perceived stress reactivity were uncorrelated. In summary, our study
indicates associations between sleep disturbances and stress reactivity were not
independent of BMI and chronic stress levels, and endocrine and perceived stress
reactivity were dissociated.
PMID- 28407211
TI - Long-term alterations in monocyte function after elective cardiac surgery.
AB - Optimal immunological homoeostasis determines the long-term recovery of patients
in the postoperative period. The functional adaptability of monocytes plays a
pivotal role in adjusting the host's response to an insult, immunostasis and long
term health, and may help to determine successful recovery. We undertook a
longitudinal analysis of the functional adaptability of monocytes in 20 patients
undergoing heart surgery with cardiopulmonary bypass, as a model of severe
stress. Using each patient's pre-cardiopulmonary bypass data as a baseline, we
investigated the characteristics of peripheral blood monocytes' functional
plasticity in-vitro before elective bypass, and three months afterwards.
Approximately 30% of subjects showed diminished monocyte plasticity, as
demonstrated by decreased monocyte differentiation into dendritic cells three
months after bypass. Diminished monocyte functional plasticity was related to
over-production of macrophage colony-stimulating factor. Adding a neutralising
antibody to macrophage colony-stimulating factor corrected the monocytes'
differentiation defect. Finally, patients with reduced monocyte plasticity had
significantly elevated serum C-reactive protein, with a concomitant increase in
cytomegalovirus IgG antibody titres, suggestive of the acquisition of immuno
suppressive traits. Our study shows that severe surgical stress resulted in a
lasting immunological defect in individuals who had seemingly recovered.
PMID- 28407212
TI - Reduced Healthcare Use and Apparent Savings with Passive Home Monitoring
Technology: A Pilot Study.
AB - OBJECTIVES: To conduct a cost analysis of ambient assisted living technology,
which is promising for improving the ability of individuals and care providers to
monitor daily activities and gain better awareness through proactive management
of health and safety. DESIGN: Three-arm cohort study. SETTING: Homes of enrollees
of a state-based healthcare plan for older adults. PARTICIPANTS: Enrollees dually
eligible for Medicare and Medicaid (N = 268). INTERVENTION: Health and safety
passive remote patient monitoring (PRPM) systems were installed in enrollees'
homes (the intervention group) with monitoring and proactive intervention of a
case manager when deviation from baseline subject behavior was detected.
MEASUREMENTS: Claims data were collected over 12 months to assess healthcare use
and costs in the intervention group and to compare use and costs with those of
two control groups: a concurrent group of enrollees who declined the technology
and a historical cohort matched on age to the participation group. RESULTS:
Although the small sample size precluded cost differences that were statistically
significant, the participant group used substantially less custodial care,
emergency department (ED) services, inpatient stays, and ED costs than the two
control groups. CONCLUSION: In this pilot study, the PRPM system was associated
with apparent healthcare cost savings. Although more cost analyses are warranted,
ambient assisted living technologies are a potentially valuable investment for
older adult care.
PMID- 28407213
TI - Analysis of multiple diverse phenotypes via semiparametric canonical correlation
analysis.
AB - Studying multiple outcomes simultaneously allows researchers to begin to identify
underlying factors that affect all of a set of diseases (i.e., shared etiology)
and what may give rise to differences in disorders between patients (i.e.,
disease subtypes). In this work, our goal is to build risk scores that are
predictive of multiple phenotypes simultaneously and identify subpopulations at
high risk of multiple phenotypes. Such analyses could yield insight into etiology
or point to treatment and prevention strategies. The standard canonical
correlation analysis (CCA) can be used to relate multiple continuous outcomes to
multiple predictors. However, in order to capture the full complexity of a
disorder, phenotypes may include a diverse range of data types, including binary,
continuous, ordinal, and censored variables. When phenotypes are diverse in this
way, standard CCA is not possible and no methods currently exist to model them
jointly. In the presence of such complications, we propose a semi-parametric CCA
method to develop risk scores that are predictive of multiple phenotypes. To
guard against potential model mis-specification, we also propose a nonparametric
calibration method to identify subgroups that are at high risk of multiple
disorders. A resampling procedure is also developed to account for the
variability in these estimates. Our method opens the door to synthesizing a wide
array of data sources for the purposes of joint prediction.
PMID- 28407214
TI - A novel link between keratoderma and cardiomyopathy: contiguous gene deletion
involving the desmoglein gene cluster.
PMID- 28407215
TI - Updated review of genetic reticulate pigmentary disorders.
AB - Reticulate pigmentary disorders are a group of disorders characterized by hyper-
and/or hypopigmented macules with varying sizes and amounts of pigment. Some of
the disorders are heritable, such as Dowling-Degos disease, dyschromatosis
universalis hereditaria, dyschromatosis symmetrica hereditaria, reticulate
acropigmentation of Kitamura and X-linked reticulate pigmentary disorder.
Although each condition possesses unique phenotypic characteristics and the
prognosis for each is somewhat different, there is a large degree of overlap
between the disorders and therefore they are difficult to differentiate in the
clinical setting. This updated review provides a clinical and molecular
delineation of these genetic reticulate pigmentary disorders and aims to
establish a concise diagnostic strategy to allow clinical dermatologists to make
an accurate diagnosis, as well as to provide useful information for clinical and
genetic counselling.
PMID- 28407217
TI - Evolution of the skin manifestations of X-linked pigmentary reticulate disorder.
PMID- 28407216
TI - Real-world stroke prevention strategies in nonvalvular atrial fibrillation in
patients with renal impairment.
AB - BACKGROUND: The data regarding stroke prevention strategies in nonvalvular atrial
fibrillation (NVAF) are limited especially in patients with renal impairment
(RI). We sought to evaluate management dilemmas in patients with concurrent NVAF
and RI in RAMSES (ReAl-life Multicenter Survey Evaluating Stroke Prevention
Strategies inTurkey) study. METHODS: We conducted a prospective, multicenter,
nation-wide registry in NVAF patients in outpatient cardiology clinics. All
consecutive patients with NVAF were enrolled in RAMSES study (ClinicalTrials.gov
identifier NCT02344901). The baseline data were collected. Glomerular filtration
rate (GFR) was estimated by Cockcroft-Gault equation. RESULTS: A total number of
6273 patients from 29 provinces of Turkey with the contribution of 83
investigators were enrolled to the study. Of the study population, 1964(33%)
patients had RI which was defined as GFR < 60 mL/min. Patients with RI had
significantly higher CHA2 DS2 VASc and HAS-BLED scores compared to those without
RI (3.9 +/- 1.5 vs. 2.9 +/- 1.5, and 2.0 +/- 1 vs. 1.4 +/- 1; P < 0.001). Prior
history of major bleeding (6.9% vs. 4.1%, P < 0.001) and stroke (16.2% vs. 11.8%,
P < 0.001) was significantly higher among individuals with concomitant RI and
NVAF. Although RI patients had a higher risk for thromboembolism, number of the
patients who did not receive any anticoagulant therapy was higher in patients
with RI than without RI (30.1 vs. 26.4%, P = 0.003). CONCLUSION: RAMSES study
showed that one-third of the patients with NVAF had RI in the real-world setting.
Although it is mandatory in most of the patients with concomitant NVAF and RI,
nearly one-third of these patients did not receive any anticoagulant therapy.
PMID- 28407218
TI - Incorporating covariates into integrated factor analysis of multi-view data.
AB - In modern biomedical research, it is ubiquitous to have multiple data sets
measured on the same set of samples from different views (i.e., multi-view data).
For example, in genetic studies, multiple genomic data sets at different
molecular levels or from different cell types are measured for a common set of
individuals to investigate genetic regulation. Integration and reduction of multi
view data have the potential to leverage information in different data sets, and
to reduce the magnitude and complexity of data for further statistical analysis
and interpretation. In this article, we develop a novel statistical model, called
supervised integrated factor analysis (SIFA), for integrative dimension reduction
of multi-view data while incorporating auxiliary covariates. The model decomposes
data into joint and individual factors, capturing the joint variation across
multiple data sets and the individual variation specific to each set,
respectively. Moreover, both joint and individual factors are partially informed
by auxiliary covariates via nonparametric models. We devise a computationally
efficient Expectation-Maximization (EM) algorithm to fit the model under some
identifiability conditions. We apply the method to the Genotype-Tissue Expression
(GTEx) data, and provide new insights into the variation decomposition of gene
expression in multiple tissues. Extensive simulation studies and an additional
application to a pediatric growth study demonstrate the advantage of the proposed
method over competing methods.
PMID- 28407219
TI - Multiple-micronutrient supplementation for women during pregnancy.
AB - BACKGROUND: Multiple-micronutrient (MMN) deficiencies often coexist among women
of reproductive age in low- to middle-income countries. They are exacerbated in
pregnancy due to the increased demands, leading to potentially adverse effects on
the mother and developing fetus. Though supplementation with MMNs has been
recommended earlier because of the evidence of impact on pregnancy outcomes, a
consensus is yet to be reached regarding the replacement of iron and folic acid
supplementation with MMNs. Since the last update of this Cochrane review,
evidence from a few large trials has recently been made available, the inclusion
of which is critical to inform policy. OBJECTIVES: To evaluate the benefits of
oral multiple-micronutrient supplementation during pregnancy on maternal, fetal
and infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy
and Childbirth Group's Trials Register (11 March 2015) and reference lists of
retrieved articles and key reviews. We also contacted experts in the field for
additional and ongoing trials. SELECTION CRITERIA: All prospective randomised
controlled trials evaluating MMN supplementation with iron and folic acid during
pregnancy and its effects on the pregnancy outcome were eligible, irrespective of
language or the publication status of the trials. We included cluster-randomised
trials, but quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS:
Two review authors independently assessed trials for inclusion and risk of bias,
extracted data and checked them for accuracy. The quality of the evidence was
assessed using the GRADE approach. MAIN RESULTS: Nineteen trials (involving
138,538 women) were identified as eligible for inclusion in this review but only
17 trials (involving 137,791 women) contributed data to the review. Fifteen of
these 17 trials were carried out in low and middle-income countries and compared
MMN supplements with iron and folic acid versus iron with or without folic acid.
Two trials carried out in the UK compared MMN with a placebo. MMN with iron and
folic acid versus iron, with or without folic acid (15 trials): MMN resulted in a
significant decrease in the number of newborn infants identified as low
birthweight (LBW) (average risk ratio (RR) 0.88, 95% confidence interval (CI)
0.85 to 0.91; high-quality evidence) or small-for-gestational age (SGA) (average
RR 0.92, 95% CI 0.86 to 0.98; moderate-quality evidence). No significant
differences were shown for other maternal and pregnancy outcomes: preterm births
(average RR 0.96, 95% CI 0.90 to 1.03; high-quality evidence), stillbirth
(average RR 0.97, 95% CI 0.87, 1.09; high-quality evidence), maternal anaemia in
the third trimester (average RR 1.03, 95% CI 0.85 to 1.24), miscarriage (average
RR 0.91, 95% CI 0.80 to 1.03), maternal mortality (average RR 0.97, 95% CI 0.63
to 1.48), perinatal mortality (average RR 1.01, 95% CI 0.91 to 1.13; high-quality
evidence), neonatal mortality (average RR 1.06, 95% CI 0.92 to 1.22; high-quality
evidence), or risk of delivery via a caesarean section (average RR 1.04; 95% CI
0.74 to 1.46).A number of prespecified, clinically important outcomes could not
be assessed due to insufficient or non-available data. Single trials reported
results for: very preterm birth < 34 weeks, macrosomia, side-effects of
supplements, nutritional status of children, and congenital anomalies including
neural tube defects and neurodevelopmental outcome: Bayley Scales of Infant
Development (BSID) scores. None of these trials reported pre-eclampsia, placental
abruption, premature rupture of membranes, cost of supplementation, and maternal
well-being or satisfaction.When assessed according to GRADE criteria, the quality
of evidence for the review's primary outcomes overall was good. Pooled results
for primary outcomes were based on multiple trials with large sample sizes and
precise estimates. The following outcomes were graded to be as of high quality:
preterm birth, LBW, perinatal mortality, stillbirth and neonatal mortality. The
outcome of SGA was graded to be of moderate quality, with evidence downgraded by
one for funnel plot asymmetry and potential publication bias.We carried out
sensitivity analysis excluding trials with high levels of sample attrition (>
20%); results were consistent with the main analysis except for the findings for
SGA (average RR 0.91, 95% CI 0.84 to 1.00). We explored heterogeneity through
subgroup analyses by maternal height and body mass index (BMI), timing of
supplementation and dose of iron. Subgroup differences were observed for maternal
BMI for the outcome preterm birth, with significant findings among women with low
BMI. Subgroup differences were also observed for maternal BMI and maternal height
for the outcome SGA, indicating a significant impact among women with higher
maternal BMI and height. The overall analysis of perinatal mortality, although
showed a non-significant effect of MMN supplements versus iron with or without
folic acid, was found to have substantial statistical heterogeneity. Subgroup
differences were observed for timing of supplementation for this outcome,
indicating a significantly higher impact with late initiation of supplementation.
The findings between subgroups for other primary outcomes were inconclusive. MMN
versus placebo (two trials): A single trial in the UK found no clear differences
between groups for preterm birth, SGA, LBW or maternal anaemia in the third
trimester. A second trial reported the number of women with pre-eclampsia; there
was no evidence of a difference between groups. Other outcomes were not reported.
AUTHORS' CONCLUSIONS: Our findings support the effect of MMN supplements with
iron and folic acid in improving some birth outcomes. Overall, pregnant women who
received MMN supplementation had fewer low birthweight babies and small-for
gestational-age babies. The findings, consistently observed in several systematic
evaluations of evidence, provide a basis to guide the replacement of iron and
folic acid with MMN supplements containing iron and folic acid for pregnant women
in low and middle-income countries where MMN deficiencies are common among women
of reproductive age. Efforts could focus on the integration of this intervention
in maternal nutrition and antenatal care programs in low and middle-income
countries.
PMID- 28407220
TI - Patient-controlled analgesia with remifentanil versus alternative parenteral
methods for pain management in labour.
AB - BACKGROUND: Multiple analgesic strategies for pain relief during labour are
available. Recently remifentanil, a short-acting opioid, has recently been used
as an alternative analgesic due to its unique pharmacological properties.
OBJECTIVES: To systematically assess the effectiveness of remifentanil
intravenous patient-controlled analgesia (PCA) for labour pain, along with any
potential harms to the mother and the newborn. SEARCH METHODS: We searched the
Cochrane Pregnancy and Childbirth Group's Trials Register (9 December 2015),
ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform
(ICTRP), handsearched congress abstracts (November 2015), and reference lists of
retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and
cluster-randomised trials comparing remifentanil (PCA) with another opioid
(intravenous (IV)/intramuscular (IM)), or with another opioid (PCA), or with
epidural analgesia, or with remifentanil (continuous IV), or with remifentanil
(PCA, different regimen), or with inhalational analgesia, or with placebo/no
treatment in all women in labour including high-risk groups with planned vaginal
delivery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
trials for inclusion, extracted data, and appraised study quality.We contacted
study authors for additional information other than incomplete outcome data. We
performed random-effects meta-analysis.To reduce the risk of random error in meta
analysis we performed trial sequential analysis. We included total zero event
trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta
analysis. We applied the Grades of Recommendation, Assessment, Development, and
Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS:
Twenty RCTs with 3569 women were included. Of those, 10 trials (2983
participants) compared remifentanil (PCA) to an epidural, four trials (216
participants) to another opioid (IV/IM), three trials (215 participants) to
another opioid (PCA), two trials (135 participants) to remifentanil (continuous
IV), and one trial (20 participants) to remifentanil (PCA, different regimen). No
trials were identified for the remaining comparisons.Methodological quality of
studies was moderate to poor. We assessed risk of bias as high for blinding
issues and incomplete outcome data in 65% and 45% of the included studies,
respectively.There is evidence of effect that women in the remifentanil (PCA)
group were more satisfied with pain relief than women in the other opioids
(IV/IM) group (standardised mean difference (SMD) 2.11, 95% confidence interval
(CI) 0.72 to 3.49, four trials, very low-quality evidence), and that women were
less satisfied compared to women in the epidural group (SMD -0.22, 95% CI -0.40
to -0.04, seven trials, very low-quality evidence).There is evidence of effect
that remifentanil (PCA) provided stronger pain relief at one hour than other
opioids administered IV/IM (SMD -1.58, 95% CI -2.69 to -0.48, three trials, very
low-quality evidence) or via PCA (SMD -0.51, 95% CI -1.01 to -0.00, three trials,
very low-quality evidence). Pain intensity was higher in the remifentanil (PCA)
group compared to the epidural group (SMD 0.57, 95% CI 0.31 to 0.84, six trials,
low-quality evidence).Data were limited on safety aspects for both the women and
the newborns. Only one study analysed maternal apnoea in a comparison of
remifentanil (PCA) versus epidural and reported that half of the women in the
remifentanil and none in the epidural group had an apnoea (very low-quality
evidence). There is no evidence of effect that remifentanil (PCA) was associated
with an increased risk for maternal respiratory depression when compared to
epidural analgesia (RR 0.91, 95% CI 0.51 to 1.62, ccc 0.01, three trials, low
quality evidence) and no reliable conclusion might be reached compared to
remifentanil (continuous IV) (all study arms included zero events, two trials,
low-quality evidence). In one trial of remifentanil (PCA) versus another opioid
(IM) three out of 18 women in the remifentanil and none out of 18 in the control
group had a respiratory depression (very low-quality evidence).There is no
evidence of effect that remifentanil (PCA) was associated with an increased risk
for newborns with Apgar scores less than seven at five minutes compared to
epidural analgesia (RR 1.26, 95% CI 0.62 to 2.57, ccc 0.01, five trials, low
quality evidence) and no reliable conclusion might be reached compared to another
opioid (IV) and compared to remifentanil (PCA, different regimen) both with zero
events in all study arms (one trial, very-low quality evidence). In one trial of
remifentanil (PCA) versus another opioid (PCA) none out of nine newborns in the
remifentanil and three out of eight in the opioid (PCA) group had Apgar scores
less than seven (very-low quality evidence).There is evidence that remifentanil
(PCA) was associated with a lower risk for the requirement of additional
analgesia when compared to other opioids (IV/IM) (RR 0.57, 95% CI 0.40 to 0.81,
three trials, moderate-quality evidence) and that it was associated with a higher
risk compared to epidural analgesia (RR 9.27, 95% CI 3.73 to 23.03, ccc 0.01, six
trials, moderate-quality evidence). There is no evidence of effect that
remifentanil (PCA) reduced the requirement for additional analgesia compared to
other opioids (PCA) (RR 0.76, 95% CI 0.45 to 1.28, three trials, low-quality
evidence).There is evidence that there was no difference in the risk for
caesarean delivery between remifentanil (PCA) and other opioids (IV/IM) (RR 0.63,
95% CI 0.30 to 1.32, ccc 0.01, four trials, low-quality evidence) and epidural
analgesia (RR 1.0, 95% CI 0.82 to 1.22, ccc 0.01, nine trials, moderate-quality
evidence), respectively. Pooled meta-analysis revealed an increased risk for
caesarean section under remifentanil (PCA) compared to other opioids (PCA) (RR
2.78, 95% CI 0.99 to 7.82, two trials, very low-quality evidence). However, a
wide range of clinically relevant and non-relevant treatment effects is
compatible with this result. AUTHORS' CONCLUSIONS: Based on the current
systematic review, there is mostly low-quality evidence to inform practice and
future research may significantly alter the current situation. The quality of
evidence is mainly limited by poor quality of the studies, inconsistency, and
imprecision. More research is needed on maternal and neonatal safety outcomes
(maternal apnoea and respiratory depression, Apgar score) and on the optimal mode
and regimen of remifentanil administration to provide highest efficacy with
reasonable adverse effects for mothers and their newborns.
PMID- 28407221
TI - Targeted next-generation sequencing identifies nine novel filaggrin gene variants
in Chinese Han patients with ichthyosis vulgaris.
PMID- 28407222
TI - Infection control practices in Mohs micrographic surgery: a U.K. national survey.
PMID- 28407223
TI - Statistical models and confounding adjustment.
PMID- 28407225
TI - Meta-analysis of the prevalence of renal cancer detected by abdominal
ultrasonography.
AB - BACKGROUND: The potential for an ultrasound-based screening programme for renal
cell carcinoma (RCC) to improve survival through early detection has been the
subject of much debate. The prevalence of ultrasound-detected asymptomatic RCC is
an important first step to establishing whether a screening programme may be
feasible. METHODS: A systematic search of MEDLINE and Embase was performed up to
March 2016 to identify studies reporting the prevalence of renal masses and RCC.
Two populations of patients were chosen: asymptomatic individuals undergoing
screening ultrasonography and patients undergoing ultrasonography for abdominal
symptoms not related to RCC. A random-effects meta-analysis was performed. Study
quality was evaluated using a validated eight-point checklist. RESULTS: Sixteen
studies (413 551 patients) were included in the final analysis. The pooled
prevalence of renal mass was 0.36 (95 per cent c.i. 0.23 to 0.52) per cent and
the prevalence of histologically proven RCC was 0.10 (0.06 to 0.15) per cent. The
prevalence of RCC was more than double in studies from Europe and North America
than in those from Asia: 0.17 (0.09 to 0.27) versus 0.06 (0.03 to 0.09) per cent
respectively. Data on 205 screen-detected RCCs showed that 84.4 per cent of
tumours were stage T1-T2 N0, 13.7 per cent were T3-T4 N0, and only 2.0 per cent
had positive nodes or metastases at diagnosis. CONCLUSION: At least one RCC would
be detected per 1000 individuals screened. The majority of tumours identified are
early stage (T1-T2).
PMID- 28407227
TI - Systematic review of pressurized intraperitoneal aerosol chemotherapy for the
treatment of advanced peritoneal carcinomatosis.
AB - BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a
minimally invasive approach under investigation as a novel treatment for patients
with peritoneal carcinomatosis of various origins. The aim was to review the
available evidence on mechanisms, clinical effects and risks. METHODS: This was a
systematic review of the literature on pressurized intraperitoneal chemotherapy
published between January 2000 and October 2016. All types of scientific report
were included. RESULTS: Twenty-nine relevant papers were identified; 16 were
preclinical studies and 13 were clinical reports. The overall quality of the
clinical studies was modest; five studies were prospective and there was no
randomized trial. Preclinical data suggested better distribution and higher
tissue concentrations of chemotherapy agents in PIPAC compared with conventional
intraperitoneal chemotherapy by lavage. Regarding technical feasibility,
laparoscopic access and repeatability rates were 83-100 and 38-82 per cent.
Surgery-related complications occurred in up to 12 per cent. Postoperative
morbidity was low (Common Terminology Criteria for Adverse Events grade 3-5
events reported in 0-37 per cent), and hospital stay was about 3 days. No
negative impact on quality of life was reported. Histological response rates for
therapy-resistant carcinomatosis of ovarian, colorectal and gastric origin were
62-88, 71-86 and 70-100 per cent respectively. CONCLUSION: PIPAC is feasible,
safe and well tolerated. Preliminary good response rates call for prospective
analysis of oncological efficacy.
PMID- 28407228
TI - Deleterious protein-altering mutations in the SCN10A voltage-gated sodium channel
gene are associated with prolonged QT.
AB - BACKGROUND: Long QT syndrome (LQT) is a pro-arrhythmogenic condition with life
threatening complications. Fifteen genes have been associated with congenital
LQT, however, the genetic causes remain unknown in more than 20% of cases.
MATERIALS AND METHODS: Eighteen patients with history of palpitations, pre
syncope, syncope and prolonged QT were referred to the Yale Cardiovascular
Genetics Program. All subjects underwent whole-exome sequencing (WES) followed by
confirmatory Sanger sequencing. Mutation burden analysis was carried out using
WES data from 16 subjects with no identifiable cause of LQT. RESULTS: Deleterious
and novel SCN10A mutations were identified in 3 of the 16 patients (19%) with
idiopathic LQT. These included 2 frameshifts and 1 missense variants (p.G810fs,
p.R1259Q, and p.P1877fs). Further analysis identified 2 damaging SCN10A mutations
with allele frequencies of approximately 0.2% (p.R14L and p.R1268Q) in 2
independent cases. None of the SCN10A mutation carriers had mutations in known
arrhythmia genes. Damaging SCN10A mutations (p.R209H and p.R485C) were also
identified in the 2 subjects on QT prolonging medications. CONCLUSION: Our
findings implicate SCN10A in LQT. The presence of frameshift mutations suggests
loss-of-function as the underlying disease mechanism. The common association with
atrial fibrillation suggests a unique mechanism of disease for this LQT gene.
PMID- 28407229
TI - Weight gain with add-on second-generation antipsychotics in bipolar disorder: a
naturalistic study.
AB - OBJECTIVE: Our aim was to investigate the prevalence and magnitude of weight gain
in-patients with bipolar disorder when treated with a second-generation
antipsychotic as an add-on treatment to a mood stabilizer in routine clinical
practice. METHODS: Data were derived from the quality register for bipolar
disorder in Sweden (BipolaR). Patients with bipolar disorder who started add-on
treatment with a SGA (n = 575) were compared at next yearly follow-up with age
and sex matched patients who were only treated with a mood stabilizer (n = 566).
The primary outcome measure was change in body weight and body mass index (BMI).
We also assessed the prevalence of clinically significant weight gain defined as
>=7% gain in body weight. RESULTS: The group that received add-on treatment with
antipsychotics neither gained more weight nor were at higher risk for a
clinically significant weight gain than the reference group. Instead, factors
associated with clinically significant weight gain were female sex, young age,
low-baseline BMI, and occurrence of manic/hypomanic episodes. CONCLUSION: We
found no evidence of an overall increased risk of weight gain for patients with
bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine
clinical setting.
PMID- 28407230
TI - Acyl-CoA synthetase short-chain family member 2 (ACSS2) is regulated by SREBP-1
and plays a role in fatty acid synthesis in caprine mammary epithelial cells.
AB - Sterol regulatory element binding protein 1 (SREBP-1) is well-known as the master
regulator of lipogenesis in rodents. Acyl-CoA synthetase short-chain family
member 2 (ACSS2) plays a key role in lipogenesis by synthesizing acetyl-CoA from
acetate for lipogenesis. ATP citrate lyase (ACLY) catalyzes the conversion of
citrate and coenzyme A to acetyl-CoA, hence, it is also important for
lipogenesis. Although ACSS2 function in cancer cells has been elucidated, its
essentiality in ruminant mammary lipogenesis is unknown. Furthermore, ACSS2 gene
promoter and its regulatory mechanisms have not known. Expression of ACSS2 was
high in lipid synthesizing tissues, and its expression increased during lactation
compared with non-lactating period. Simultaneous knockdown of both ACSS2 and ACLY
by siRNA in primary goat mammary epithelial cells decreased (p < 0.05) the mRNA
abundance of genes associated with de novo fatty acid synthesis (FASN, ACACA,
SCD1) and triacylglycerol (TAG) synthesis (DGAT1, DGAT2, GPAM, and AGPAT6). Genes
responsible for lipid droplet formation and secretion (PLIN2 and PLIN3) and fatty
acid oxidation (ATGL, HSL, ACOX, and CPT1A) all decreased (p < 0.05) after ACSS2
and ACLY knockdown. Total cellular TAG content and lipid droplet formation also
decreased. Use of a luciferase reporter assay revealed a direct regulation of
ACSS2 by SREBP-1. Furthermore, SREBP-1 interacted with an SRE (SREBP response
element) spanning at -475 to -483 bp on the ACSS2 promoter. Taken together, our
results revealed a novel pathway that SREBP-1 may regulate fatty acid and TAG
synthesis by regulating the expression of ACSS2.
PMID- 28407231
TI - An inhibitory RNA aptamer against the lambda cI repressor shows transcriptional
activator activity in vivo.
AB - RNA aptamers are one of the promising components for constructing artificial
genetic circuits. In this study, we developed a transcriptional activator based
on an RNA aptamer against one of the most frequently applied repressor proteins,
lambda phage cI. In vitro selection (Systematic Evolution of Ligands by
EXponential enrichment) and following in vivo screening identified an RNA aptamer
with the intended transcriptional activator activity from an RNA pool containing
a 40-nucleotide long random region. Quantitative analysis showed a 35-fold
elevation of reporter expression upon aptamer expression. These results suggest
that the diversity of artificial transcriptional activators can be extended by
employing RNA aptamers against repressor proteins to broaden the parts for
constructing genetic circuits.
PMID- 28407232
TI - Observed survival benefit of mild therapeutic hypothermia reanalysing the
Circulation Improving Resuscitation Care trial.
AB - BACKGROUND: Mild therapeutic hypothermia is argued being beneficial for outcome
after cardiac arrest. MATERIALS AND METHODS: Retrospective analysis of
Circulation Improving Resuscitation Care (CIRC) trial data to assess if
therapeutic cooling to 33 +/- 1 degrees C core temperature had an association
with survival. Of 4231 adult, out-of-hospital cardiac arrests of presumed cardiac
origin initially enrolled, eligibility criteria for therapeutic hypothermia were
met by 1812. Logistic regression was undertaken in a stepwise fashion to account
for the impact on outcome of each significant difference and for the variable of
interest between the groups. RESULTS: Out-of- and in-hospital cooled were 263
(15%), only after admission cooled were 230 (13%) and not cooled were 357 (20%)
patients. The group cooled out of- and in hospital had 98 (37%) survivors as
compared to the groups cooled in hospital only [80 (35%)] and of those not cooled
[68 (19%)]. After adjusting for known covariates (sex, age, witnessed cardiac
arrest, no- and low-flow time, shockable initial rhythm, random allocation,
bystander cardiopulmonary resuscitation and percutaneous coronary intervention),
the odds ratio for survival comparing no cooling to out-of- plus in-hospital
cooling was 0.53 [95% confidence interval (CI): 0.46-0.61, P < 0.001], and
comparing to in-hospital cooling only was 0.67 (95% CI: 0.50-0.89, P = 0.006).
CONCLUSION: Mild therapeutic hypothermia initiated out of hospital and/or in
hospital was associated with improved survival within this secondary analysis of
the CIRC cohort compared to no therapeutic hypothermia.
PMID- 28407233
TI - Language disorder and retrospectively reported sexual abuse of girls: severity
and disclosure.
AB - BACKGROUND: Despite emerging evidence for an association between communication
disorders and maltreatment, little research has examined sexual abuse
characteristics or disclosure experiences among individuals with language
disorder (LD). Given that communication difficulties may constitute a barrier to
disclosure, the disclosure experiences among individuals with and without
communication difficulties may also differ. METHODS: Five-year-old children
identified with a language and/or speech disorder from a nonclinical community
sample and a control group were followed to adulthood in a prospective
longitudinal study. At age 31, participants completed a behaviorally specific
questionnaire on experiences of sexual abuse and questionnaires on disclosure
experiences and social reactions to disclosure. Due to low endorsement of sexual
victimization among male participants and low sample size, results are reported
for women only and exclude nine participants with speech disorder without LD.
Participation rates were 28 of 40 in the LD cohort and 45 of 51 controls. Sexual
victimization severity was defined using an index combining five indicators
(duration, invasiveness, relationship to perpetrator, coercive tactics used, and
number of perpetrators). Subthreshold sexual victimization was defined as a
single, noncontact incident with a perpetrator unknown to the child; experiences
with greater severity were classified as child sexual abuse. RESULTS: Among women
who reported sexual victimization by age 18, invasiveness and overall severity
were greater in the LD cohort than in the control cohort. Women in the LD cohort
(43%) were more likely than controls (16%) to report child sexual abuse,
excluding subthreshold experiences. There were no differences between cohorts in
probability of disclosure, latency to disclosure, or social reactions.
CONCLUSIONS: Women with a history of child LD in a nonclinical sample reported
substantial child sexual abuse experiences. Implications for understanding
associations between LD and mental health and for prevention and early
intervention are discussed.
PMID- 28407234
TI - Mediterranean diet decreases adolescent waist circumference.
AB - BACKGROUND: To explore the effects of a multicomponent-multilevel school-based
educational intervention on the nutritional habits and abdominal obesity indices
of a representative adolescent sample. MATERIALS AND METHODS: A representative
sample of 1610 adolescents aged 12-17 years in 23 public high schools of three
municipalities in the Attica region in Greece participated in a programme funded
by the European Union (August 2013-August 2014). Participants underwent dietary
assessment with the use of the Mediterranean Diet Quality Index in children and
adolescents (KIDMED), blood pressure (BP) assessment and screening for general
and abdominal obesity by measuring body mass index, waist circumference (WC) and
waist-to-height ratio (WHtR), at baseline and following a 6-month school-based
intervention. The intervention involved nutritional education, physical activity
and body image awareness using a multilevel approach to the adolescent
participants, their parents, school teachers and health staff. RESULTS: Analysis
included 1032 adolescents (mean age +/- SD 14.1 +/- 1.6 years). Following
intervention, mean KIDMED score +/- SD increased significantly from 5.6 +/- 2.4
to 5.8 +/- 2.4 (P = 0.004). Higher percentage of boys (P = 0.028) and younger
adolescents (P < 0.001) had optimal KIDMED scores >= 8. Significant decreases
were observed in overweight and obesity (P = 0.033), mean systolic (P = 0.049)
and diastolic (P < 0.001) BP, WC (P < 0.001) and WHtR (P < 0.001). WC decreased
as the KIDMED score increased (P = 0.020). Living with both parents (P = 0.036),
higher maternal (P = 0.039) and paternal (P = 0.004) education and having a
younger father (P = 0.034) were associated with better adherence to Mediterranean
diet, post-intervention. CONCLUSIONS: Increased adherence to MD was associated
with decreased WC, indicating a potential of multicomponent-multilevel school
based interventions to combat adolescent abdominal obesity.
PMID- 28407235
TI - Magazine Influence on Cartridge Case Ejection Patterns with Glock Pistols.
AB - In this study, the cartridge case ejection patterns of six different Glock model
pistols (one specimen per model) were compared under three conditions: firing
with a loaded magazine, an empty magazine, and without magazine. The distances,
covered by the ejected cartridge cases given these three conditions, were
compared for each of the six models. A significant difference was found between
the groups of data for each of the tested specimens. This indicates that it is
important that, to reconstruct a shooting scene incident based on the ejection
patterns of a pistol, test shots are fired with the same pistol type and under
the correct magazine condition.
PMID- 28407236
TI - Processes to Preserve Spice and Herb Quality and Sensory Integrity During
Pathogen Inactivation.
AB - Selected processing methods, demonstrated to be effective at reducing Salmonella,
were assessed to determine if spice and herb quality was affected. Black
peppercorn, cumin seed, oregano, and onion powder were irradiated to a target
dose of 8 kGy. Two additional processes were examined for whole black peppercorns
and cumin seeds: ethylene oxide (EtO) fumigation and vacuum assisted-steam (82.22
degrees C, 7.5 psia). Treated and untreated spices/herbs were compared (visual,
odor) using sensory similarity testing protocols (alpha = 0.20; beta = 0.05;
proportion of discriminators: 20%) to determine if processing altered sensory
quality. Analytical assessment of quality (color, water activity, and volatile
chemistry) was completed. Irradiation did not alter visual or odor sensory
quality of black peppercorn, cumin seed, or oregano but created differences in
onion powder, which was lighter (higher L* ) and more red (higher a* ) in color,
and resulted in nearly complete loss of measured volatile compounds. EtO
processing did not create detectable odor or appearance differences in black
peppercorn; however visual and odor sensory quality differences, supported by
changes in color (higher b* ; lower L* ) and increased concentrations of most
volatiles, were detected for cumin seeds. Steam processing of black peppercorn
resulted in perceptible odor differences, supported by increased concentration of
monoterpene volatiles and loss of all sesquiterpenes; only visual differences
were noted for cumin seed. An important step in process validation is the
verification that no effect is detectable from a sensory perspective.
PMID- 28407237
TI - Cytoskeletal remodeling and regulation of cell fate in the hypertensive neonatal
pulmonary artery in response to stress.
AB - Neonatal pulmonary hypertension (PHN) is a lethal progressive disease that occurs
in prenatal circulatory transition. Mechanical wall strain caused by cardiac
pulsation integrates with hypoxia to generate rapidly progressive myocyte
cytoskeleton disassembly and failure to exert force generation. The physiological
responses to such an interaction have not been investigated. The persistent
phenotype does not respond to traditional vasodilator therapy; hence, there is a
need for new treatment strategies to improve the morbidity and mortality
outcomes. We reviewed the current research methods, models, and markers of
persistent PHN relevant to oxidative and nitrosative stress as well as cell fate
commitment, with an emphasis on apoptosis and proliferation. We surveyed
potential investigations into the role of senescence in neonatal PHN cell fate
decision programming during vasodilator treatment and suggested putative drug
targets to improve clinical outcomes. We identified important signaling
intermediates of senescence and cell cycle entry regulation in hypertensive
pulmonary arterial tissues.
PMID- 28407238
TI - Quercetin, Hyperin, and Chlorogenic Acid Improve Endothelial Function by
Antioxidant, Antiinflammatory, and ACE Inhibitory Effects.
AB - In recent years, the blueberry cultivation and processing industry developed
quickly because blueberries are super-fruit with healthy function. Blueberry
leaves are byproducts of the blueberry industry, which are rich in bioactive
phenolics, such as quercetin (Q), hyperin (H), and chlorogenic acid (C). This
study investigated protective effects of 3 phenolics (Q, H, and C) from leaves of
rabbiteye blueberry Vaccinium ashei on human umbilical vein endothelial cells.
The results showed that all these 3 phenolics could improve endothelial function
by inhibiting oxidative damage and proinflammatory cytokines caused by tumor
necrosis factor-alpha (TNF-alpha). The cell vitalities of endothelial cells
pretreated with Q, H, and C were higher than those stimulated with TNF-alpha
only. These phenolics could decrease reactive oxygen species and xanthine oxidase
1 levels and increase superoxide dismutase and heme oxygenase-1 levels in
endothelial cells. They also could decrease the protein expressions of
intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and
monocyte chemotactic protein-1 induced by TNF-alpha. In addition, Q, H, and C
also exhibited vasodilatory effect by reducing the angiotensin I-converting
enzyme (ACE) protein levels in endothelial cells. Mostly 3 phenolics exhibited
bioactivities as a function of concentration, but the effects not always depended
on the concentration. The antioxidant and antiinflammatory effects of Q seemed to
be more pronounced than H; however, H exhibited higher cell vitalities. The
results indicated that phenolics from rabbiteye blueberry leaves could be
potential antioxidants, inflammation and ACE inhibitors, and rabbiteye blueberry
leaves provide a new resources of phytochemicals beneficial for cardiovascular
health.
PMID- 28407239
TI - The therapeutic potential of targeting the BRAF mutation in patients with
colorectal cancer.
AB - Colorectal cancer is among the most lethal malignancies globally. BRAF is a
member of the RAS/RAF/MEK/ERK signaling pathway. Its constitutive activation can
result in increased cellular growth, development, invasion, and resistance to
therapy. A mutation of the BRAF gene is present in 5-10% of metastatic colorectal
cancers. BRAF mutations have been found to predict a lack of benefit to anti-EGFR
therapy in metastatic CRC. Furthermore, CRC containing the BRAF V600E mutation
display an innate resistance to BRAF inhibitors. The mechanisms of cell
resistance can be explained at least in part by ERK dependent and ERK in
dependent pathway. Clinical trials evaluating the combinations of BRAF, PI3K,
EGFR, and/or MEK inhibitors have revealed promising activity in BRAF mutant
containing CRCs. There may be some benefit from future studies that focus on
improving the efficacy of combined therapy in CRC with respect to the sustained
effects. The aim of current review is to give an overview about the current
status and prospective regarding the therapeutic potential of targeting BRAF
mutant colorectal cancer.
PMID- 28407240
TI - Evolution of Taste Compounds of Dezhou-Braised Chicken During Cooking Evaluated
by Chemical Analysis and an Electronic Tongue System.
AB - This paper aimed to study the time course changes in taste compounds of Dezhou
braised chicken during the entire cooking process mainly consisting of deep
frying, high-temperature boiling, and low-temperature braising steps. For this
purpose, meat samples at different processing stages were analyzed for 5'
nucleotides and free amino acids, and were also subjected to electronic tongue
measurements. Results showed that IMP, Glu, Lys, and sodium chloride were the
main compounds contributing to the taste attributes of the final product. IMP and
Glu increased in the boiling step and remained unchanged in the following
braising steps. Meanwhile, decrease in Lys content and increase in sodium
chloride content were observed over time in both boiling and braising steps.
Intensities for bitterness, saltiness, and Aftertaste-B obtained from the
electronic tongue analysis were correlated with the concentrations of these above
chemical compounds. Therefore, the electronic tongue system could be applied to
evaluate the taste development of Dezhou-braised chicken during processing.
PMID- 28407241
TI - Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon
tissues via mTORC1 signaling.
AB - Leptin, an adipocyte-derived cytokine associated with bone metabolism, is
believed to play a critical role in the pathogenesis of heterotopic ossification
(HO). The effect and underlying action mechanism of leptin were investigated on
osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro and the
HO formation in rat tendons. Isolated rat TDSCs were treated with various
concentrations of leptin in the presence or absence of mTORC1 signaling specific
inhibitor rapamycin in vitro. A rat model with Achilles tenotomy was employed to
evaluate the effect of leptin on HO formation together with or without rapamycin
treatment. In vitro studies with TDSCs showed that leptin increased the
expression of osteogenic biomarkers (alkaline phosphatase, runt-related
transcription factor 2, osterix, osteocalcin) and enhanced mineralization of
TDSCs via activating the mTORC1 signal pathway (as indicated by phosphorylation
of p70 ribosomal S6 kinase 1 and p70 ribosomal S6). However, mTORC1 signaling
blockade with rapamycin treatment suppressed leptin-induced osteogenic
differentiation and mineralization. In vivo studies showed that leptin promoted
HO formation in the Achilles tendon after tenotomy, and rapamycin treatment
blocked leptin-induced HO formation. In conclusion, leptin can promote TDSC
osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in
both vitro and vivo model, which provides a new potential therapeutic target for
HO prevention.
PMID- 28407242
TI - The role of autophagy in pro-inflammatory responses of microglia activation via
mitochondrial reactive oxygen species in vitro.
AB - Microglia over-activation contributes to neurodegenerative processes by
neurotoxin factors and pro-inflammatory molecules of pro-inflammatory processes.
Mitochondrial reactive oxygen species (ROS) and autophagy pathway might be
involved in microglial activation, but the underlying mechanism is unclear. Here,
we regulated autophagy pathway of microglia in vitro by autophagy inhibition (3
methyladenine treatment, siRNA-Beclin 1 or siRNA-ATG5 transfection) or induction
(rapamycin treatment) in murine microglial BV-2 cells or cultured primary mouse
microglial cells. And we found that autophagy inhibition could sensitize
mitochondrial profile and microglial activation of cultured microglial cells,
demonstrated by significant production of mitochondrial ROS, loss of
mitochondrial membrane potential, secretion of pro-inflammatory cytokines
including interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 12 (IL
12) and tumor necrosis factor alpha and marked activation of mitogen-activated
proteinkinases (MAPKs) and nuclear factor kappaB (NF-kappaB). These effects could
be blocked by specific inhibitors of MAPK and NF-kappaB or mitochondrial
antioxidants, Mito-TEMPO. Meanwhile, induction of autophagy with rapamycin
treatment could significantly suppress microglial inflammatory responses,
mitochondrial ROS production, activation of MAPKs and NF-kappaB. Taken together,
our in vitro results from primary cultured microglia and BV-2 cell lines
indicated that autophagy inhibition might participate in brain macrophage or
microglia over-activation and mitochondrial ROS generation might be involved in
the regulatory microglial pro-inflammatory responses.
PMID- 28407243
TI - Simulations of membrane-bound diglycosylated human prion protein reveal potential
protective mechanisms against misfolding.
AB - Prion diseases are associated with the misfolding of the prion protein (PrP) from
its normal cellular form (PrPC ) to its infectious scrapie form (PrPSc ). Post
translational modifications in PrP in vivo can play an important role in
modulating the process of misfolding. To gain more insight into the effects of
post-translational modifications in PrP structure and dynamics and to test the
hypothesis that such modifications can interact with the protein, we have
performed molecular dynamics simulations of diglycosylated human PrPC bound to a
lipid bilayer via a glycophosphatidylinositol anchor. Multiple simulations were
performed at three different pH ranges to explore pH effects on structure and
dynamics. In contrast to simulations of protein-only PrPC , no large effects were
observed upon lowering the pH of the system. The protein tilted toward the
membrane surface in all of the simulations and the putative PrPSc oligomerization
sites became inaccessible, thereby offering a possible protective mechanism
against PrPSc -induced misfolding of PrPC .
PMID- 28407244
TI - Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite.
AB - Cigarette smoke is associated to pathological weakening of bone tissue, being
considered an important playmaker in conditions such as osteoporosis and
periodontal bone loss. In addition, it is also associated with an increased risk
of failure in bone regeneration strategies. The present work aimed to
characterize the effects of nicotine on human osteoclastogenesis over a
hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or
presence of the osteoclastogenesis enhancers M-CSF and RANKL, and were further
treated with nicotine levels representative of the concentrations observed in the
plasma and saliva of smokers. It was observed that nicotine at low concentrations
elicit an increase in osteoclast differentiation, but only in the presence of M
CSF and RANKL it was also able to significantly increase the resorbing ability of
osteoclasts. A slight downregulation of NFkB pathway and an increase in the
production of TNF-alpha and, particularly PGE2, were involved in the observed
effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects,
causing a decrease in cell density. In conclusion, nicotine at levels found in
the plasma of the smokers, has the ability to act directly on osteoclast
precursors, inducing its osteoclastogenic differentiation. The stimulatory
behavior appears to be dependent on the stage of osteoclastic differentiation of
the precursor cells, which means, in the absence of M-CSF and RANKL, it only
favors the initial stages of osteoclast differentiation, while in the presence of
the growth factors, a significant increase in their resorbing ability is also
achieved.
PMID- 28407245
TI - Transvaginal primary layered repair of iatrogenic vesicovaginal fistula.
PMID- 28407246
TI - Trimodality therapy for Pancoast tumors: T4 is not a contraindication to radical
surgery.
AB - OBJECTIVE: This study aims to evaluate the impact of T stage and extended surgery
on the outcome of patients with Pancoast tumors after induction chemoradiation
therapy. METHODS: Forty-six consecutive patients who underwent chemoradiation
therapy (platin-based, 45-66 Gy) followed by surgery between 1998 and 2013 were
retrospectively reviewed and analyzed. RESULTS: In 28 (61%) patients with T4
tumors, extended procedures (more than rib resection) were performed. There were
37 (80%) lobectomies, 6 (13%) pneumonectomies, and 3 (7%) sublobar resections. A
total of 44 (96%) patients had R0 resection. About 30-day mortality was 0%, major
surgical complications occurred in 9 (19.6%) patients. Overall survival (OS) at 5
years was 63%. Disease-free survival (DFS) at 5-years was 45%. At multivariate
cox regression analysis adjusted for clinical factors, T factor (T3/T4) and
extended surgical procedures did not impact survival. However, pathological
positive N stage had a negative impact on OS and lack of pathological response
negatively impacted both OS and DFS. CONCLUSION: Trimodality treatment including
radical resection for Pancoast tumors provides good surgical outcome and
favorable long-term results. Survival of patients with T4 tumors and extended
surgical procedures comparable to that of patients with T3 tumors undergoing rib
resection only.
PMID- 28407248
TI - Evolutionary priority effects persist in anthropogenically created habitats, but
not through nonnative plant invasion.
AB - Evolutionary priority effects, where early-arriving lineages occupy niche space
via diversification and preclude dominance of later arrivals, have been observed
in alpine and forest communities. However, the potential for evolutionary
priority effects to persist in an era of rapid global change remains unclear.
Here, we use a natural experiment of historical disturbance in New Zealand to
test whether anthropogenic changes in available habitat and nonnative invasion
eliminate the role of evolutionary priority effects in community assembly. We
also test whether evolutionary priority effects diminish with decreasing resource
availability. Older plant clades, as estimated by clade crown age, were
relatively more abundant in both primary and secondary grassland. Relative
abundance in primary grassland decreased with clade stem age, but only weakly.
However, for both clade age estimates, relative abundance decreased with age when
nonnative biomass was high and soil moisture was low. Our data show that patterns
in community structure consistent with evolutionary priority effects can occur in
both primary and secondary grasslands, the latter created by anthropogenic
disturbance. However, nonnative invasion may overwhelm the effect of immigration
timing on community dominance, possibly as a result of high immigration rates and
preadaptation to anthropogenically modified environments.
PMID- 28407247
TI - Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy
for breast cancer: A multicenter trial.
AB - OBJECTIVE: We hypothesized that the Oncotype Dx(r) 21-gene Recurrence Score (RS)
could guide neoadjuvant systemic therapy (NST) to facilitate breast conserving
surgery (BCS) for hormone receptor positive (HR+) breast cancers. METHODS: This
study enrolled patients with HR+, HER2-negative, invasive breast cancers not
suitable for BCS (size >= 2 cm). Core needle biopsy blocks were tested. For
tumors with RS < 11, patients received hormonal therapy (NHT); patients with RS >
25 tumors received chemotherapy (NCT); patients with RS 11-25 were randomized to
NHT or NCT. Primary endpoint was whether 1/3 or more of randomized patients
refused assigned treatment. RESULTS: Sixty-four patients were enrolled. Of 33
patients with RS 11-25, 5 (15%) refused assignment to NCT. This was significantly
lower than the 33% target (binomial test, P = 0.0292). Results for clinical
outcomes (according to treatment received for 55 subjects) included successful
BCS for 75% of tumors with RS < 11 receiving NHT, 72% for RS 11-25 receiving NHT,
64% for RS 11-25 receiving NCT, and 57% for RS > 25 receiving NCT. CONCLUSIONS:
Using the RS to guide NST is feasible. These results suggest that for patients
with RS < 25 NHT is a potentially effective strategy.
PMID- 28407249
TI - Healthcare Quality: A Concept Analysis.
AB - Worsening quality indicators of health care shake public trust. Although safety
and quality of care in hospitals can be improved, healthcare quality remains
conceptually and operationally vague. Therefore, the aim of this analysis is to
clarify the concept of healthcare quality. Walker and Avant's method of concept
analysis, the most commonly used in nursing literature, provided the framework.
We searched general and medical dictionaries, public domain websites, and 5
academic literature databases. Search terms included health care and quality, as
well as healthcare and quality. Peer-reviewed articles and government
publications published in English from 2004 to 2016 were included. Exclusion
criteria were related concepts, discussions about the need for quality care, gray
literature, and conference proceedings. Similar attributes were grouped into
themes during analysis. Forty-two relevant articles were analyzed after excluding
duplicates and those that did not meet eligibility. Following thematic analysis,
4 defining attributes were identified: (1) effective, (2) safe, (3) culture of
excellence, and (4) desired outcomes. Based on these attributes, the definition
of healthcare quality is the assessment and provision of effective and safe care,
reflected in a culture of excellence, resulting in the attainment of optimal or
desired health. This analysis proposes a conceptualization of healthcare quality
that defines its implied foundational components and has potential to improve the
provision of quality care. Theoretical and practice implications presented
promote a fuller, more consistent understanding of the components that are
necessary to improve the provision of healthcare and steady public trust.
PMID- 28407250
TI - The Relationship Between Work-Family Conflict and Job Satisfaction Among Hospital
Nurses.
AB - AIMS: This study aimed to explore the incidence of work-family conflict and the
association between work-family conflict and satisfaction level among Jordanian
nurses. METHODS: Self-administered questionnaires were used to collect data from
a convenience sample of 333 Jordanian nurses using a descriptive, cross
sectional, correlational design. RESULTS: The results revealed that nurses were
exposed to both subtypes of work and family conflict, but they experienced the
work-to-family conflict more than the family-to-work conflict. Both subtypes of
work and family conflict were correlated negatively with age and positively with
the number of children. Being female and absence of child care facilities at
workplace had positive effects on the occurrence of work-to-family conflict.
Finally, the negative and significant relationship between the work and family
conflict and the job satisfaction level was supported. CONCLUSIONS/IMPLICATIONS
FOR PRACTICE: Those findings imply that nurse administrators and policy makers
should establish different strategies to support the balance between the nurses'
family life and nurses' work life such as child care and elder care services and
other fringe benefits. Hospitals have to promote themselves as work environments
that support job satisfaction to attract nurses, hence increasing patients'
satisfaction and quality of nursing care.
PMID- 28407252
TI - Combined endonasal and eyelid approach for management of extensive frontal sinus
inverting papilloma.
AB - OBJECTIVES: Sinonasal inverting papilloma (IP) is a benign but locally aggressive
mucosal neoplasm with a high recurrence rate. Extension into the frontal sinus
presents surgical challenges for endonasal resection. This study presents an
orbitofrontal approach for managing extensive IP. STUDY DESIGN: Case series.
METHODS: Four patients seen between 2012 and 2016 with biopsy-proven IP with
lateral frontal sinus extension underwent a combined endonasal and transpalpebral
approach for tumor resection. Patient demographic data, preoperative
characteristics, imaging, and follow-up data were compiled through retrospective
chart review. Patients were selected for this approach when the tumor extended to
the posterior frontal sinus wall, lateral frontal sinus recess, and orbit. Tumors
were first approached endonasally until the frontal recess was reached. A Draf
IIB or Draf III procedure was then performed to gain better exposure.
Orbitofrontal exposure was achieved through an upper eyelid incision.
Miniorbitofrontal craniotomy window was designed based on tumor location.
Resection of the frontal and orbital extension was enhanced by endoscopic
assisted dissection through the orbitofrontal window. RESULTS: The transpalpebral
approach provided access to all walls of the ipsilateral frontal sinus, the
intersinus septum, and the medial aspect of the contralateral sinus. Complete
tumor resection was achieved in all patients. There were no orbital
complications, no visible eyelid asymmetry or scarring, and all patients had
preserved forehead sensation. There were no recurrences on follow-up. CONCLUSION:
Combining a transpalpebral orbitofrontal craniotomy with the endonasal approach
allows complete resection of invasive IP with extension into the frontal sinus.
This is achieved with great cosmetic results. LEVEL OF EVIDENCE: 4. Laryngoscope,
128:3-9, 2018.
PMID- 28407251
TI - Investigating hyperventilation syndrome in patients suffering from empty nose
syndrome.
AB - OBJECTIVES/HYPOTHESIS: Patients with empty nose syndrome (ENS) following
turbinate surgery often complain about breathing difficulties. We set out to
determine if dyspnea in patients with ENS was associated with hyperventilation
syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be
explained by HVS. STUDY DESIGN: Observational prospective study. METHODS: All
consecutive patients referred to our center for ENS over 1 year were invited to
participate. Patients completed the Nijmegen score and underwent a
hyperventilation provocation test (HVPT) and arterial blood gas and
cardiopulmonary tests. HVS was defined by a delayed return of the end-tidal
partial pressure of carbon dioxide in the expired gas to baseline during HVPT.
Patients with HVS were asked to complete the Sinonasal Outcome Test (SNOT)-16
questionnaire before and after a specific eight-session respiratory
rehabilitation program. RESULTS: Twenty-two of the 29 patients referred for ENS
during the study period were eligible for inclusion and underwent a complete
workup. HVS was diagnosed in 17 of these patients (77.3%). In the five patients
who completed the SNOT-16, the score was significantly lower after
rehabilitation. CONCLUSIONS: This study suggests that HVS is frequent in patients
with ENS, and that symptoms can be improved by respiratory rehabilitation.
Pathophysiological links between ENS and HVS deserve to be further explored.
LEVEL OF EVIDENCE: 2b Laryngoscope, 127:1983-1988, 2017.
PMID- 28407253
TI - Treatment of tibial diaphyseal fractures following plateless tibial tuberosity
advancement to manage cranial cruciate disease.
AB - OBJECTIVE: To report diaphyseal fractures of the proximal tibia following tibial
tuberosity advancement without plate stabilisation for the management of cranial
cruciate ligament rupture in dogs. METHODS: Members of the British Veterinary
Orthopaedic Association's online discussion forum were invited to submit revision
cases of tibial diaphyseal fracture following tibial tuberosity advancement
without plate fixation. Data collected included signalment, surgical revision
technique, pre- and postoperative revision radiographic findings, complications
and veterinary assessment. Owners were invited to complete the Liverpool
Osteoarthritis in Dogs questionnaire. RESULTS: A total of 17 dogs were included
in the study. Eleven dogs had OrthoFoam-wedge modified Maquet procedures and six
had the tibial tuberosity advancement rapid procedure. Tibial tuberosity
advancement was maintained in 14/17 cases. Postrevision surgery complications
occurred in eight cases: minor complications in 3/17 dogs; major in 5/17 and no
catastrophic complications. Surgical site infection was the most common
complication (4/8). Final clinical outcome found 8/17 of dogs to have excellent,
8/17 satisfactory and 1/17 poor clinical outcome. The median Liverpool
Osteoarthritis in Dogs score was 12/52 (range 2 to 28). Final outcome was 6/13
owners that were very satisfied, 2/13 owners indifferent and 5/13 owners very
disappointed. CLINICAL SIGNIFICANCE: This is the first case series reporting
tibial diaphyseal fractures following tibial tuberosity advancement without plate
stabilisation. The authors report here a wide spectrum of potential fixation
strategies should one of these fractures occur.
PMID- 28407255
TI - Prevertebral muscle flap for internal carotid artery coverage during
oropharyngeal transoral surgery.
PMID- 28407254
TI - In response to Endoscopic-assisted transmastoid decompression of petrous apex
cholesterol granuloma.
PMID- 28407256
TI - Phytaspase-mediated precursor processing and maturation of the wound hormone
systemin.
AB - Peptide hormones are implicated in many important aspects of plant life and are
usually synthesized as precursor proteins. In contrast to animals, data for plant
peptide hormone maturation are scarce and the specificity of processing enzyme(s)
is largely unknown. Here we tested a hypothesis that processing of prosystemin, a
precursor of tomato (Solanum lycopersicum) wound hormone systemin, is performed
by phytaspases, aspartate-specific proteases of the subtilase family. Following
the purification of phytaspase from tomato leaves, two tomato phytaspase genes
were identified, the cDNAs were cloned and the recombinant enzymes were obtained
after transient expression in Nicotiana benthamiana. The newly identified tomato
phytaspases hydrolyzed prosystemin at two aspartate residues flanking the
systemin sequence. Site-directed mutagenesis of the phytaspase cleavage sites in
prosystemin abrogated not only the phytaspase-mediated processing of the
prohormone in vitro, but also the ability of prosystemin to trigger the systemic
wound response in vivo. The data show that the prohormone prosystemin requires
processing for signal biogenesis and biological activity. The identification of
phytaspases as the proteases involved in prosystemin maturation provides insight
into the mechanisms of wound signaling in tomato. Our data also suggest a novel
role for cell death-related proteases in mediating defense signaling in plants.
PMID- 28407257
TI - Chronic Disease and Mobile Technology: An Innovative Tool for Clinicians.
AB - Chronic disease is common, costly and the epidemic of the 21st century. Primary
care providers seek new and innovative approaches to prevent chronic illness.
Since the majority of chronic illness management occurs outside a physician's
office, providers must use different techniques to support daily self-management
of any chronic illness. Assisting the individual to develop life skills to
support self-management is one way to improve patient outcomes. Technology, that
is easily accessed, may provide an additional method to develop and individual's
self-management skills to prevent diabetes.
PMID- 28407258
TI - A cardiovascular prescreening protocol for unmonitored in-office laryngology
procedures.
AB - OBJECTIVES: Currently, there are no cardiovascular (CV) preprocedure screening
parameters for patients undergoing in-office laryngeal procedures (IOLP). Studies
have shown significant changes in CV measures for IOLP. The aim was to develop
and evaluate a pre-IOLP CV screening protocol. METHODS: Review of IOLP literature
and consultation with an anesthesiologist and cardiologist led to the development
of CV parameters and questions related to four metabolic equivalents (METS) of
work as a patient-screening tool before IOLP. A separate cohort was screened with
only a modified CV protocol. All patients were screened for heart rate (HR) and
blood pressure (BP) elevation prior to the procedure. Need for further CV
evaluation was characterized as systolic blood pressure BP >160, diastolic BP
>100, and/or HR >110 beats/minute. Patients whose BP/HR exceeded these values
were referred to their primary care physician (PCP) before re-screening. If
parameters were exceeded again at the second screen, then the procedure was done
under monitored anesthesia care. RESULTS: The first study phase included 56
patients. The fail rate was 40% largely related to four METS of work. The second
study phase included 440 patients. The screen fail rate was 15 patients of 572
(2.6%). Of these, 12 patients of 132 (9.1%) failed the initial screen and were
sent to their PCP for further evaluation, and five of 440 (1.4%) patients failed
on the day of the procedure. Overall, five of 440 (1.5%) patients would qualify
to have their site of service changed for their laryngology procedure from an
unmonitored to a monitored setting due to the prescreening criteria. CONCLUSION:
Few patients needed further workup based upon the in-office CV parameters set in
this study. Patients with CV risk factors were identified by the screening
protocol. Having established hemodynamic parameters in place may improve the
safety of IOLP with a very low physician burden. LEVEL OF EVIDENCE: 2b
Laryngoscope, 127:1845-1849, 2017.
PMID- 28407259
TI - The Verticillium-specific protein VdSCP7 localizes to the plant nucleus and
modulates immunity to fungal infections.
AB - Fungal pathogens secrete effector proteins to suppress plant basal defense for
successful colonization. Resistant plants, however, can recognize effectors by
cognate R proteins to induce effector-triggered immunity (ETI). By analyzing
secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a
novel secreted protein VdSCP7 that targets the plant nucleus. The green
fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear
localization signal motif or with additional nuclear export signal was
transiently expressed in Nicotiana benthamiana, and investigated for induction of
plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized
by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7
gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and
altered the plant's susceptibility to the pathogens Botrytis cinerea and
Phytophthora capsici. The immune response activated by VdSCP7 was highly
dependent on its initial extracellular secretion and subsequent nuclear
localization in plants. Knockout of the VdSCP7 gene significantly enhanced V.
dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae
and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector
protein that targets the host nucleus to modulate plant immunity, and suggest
that plants can recognize VdSCP7 to activate ETI during fungal infection.
PMID- 28407260
TI - The Value of Nursing Care: A Concept Analysis.
AB - AIM: To report an analysis of the concept of value of nursing care. BACKGROUND:
Value-based health care delivery and reimbursement models are focused on value as
a product of quality and cost. Nursing care provides tangible and intangible
contributions to patient and organizational outcomes. The nursing profession must
be able to proactively and effectively communicate the value of nursing care.
DESIGN: Concept analysis. DATA SOURCES: Thirty-five separate sources were chosen
from database searches of CINAHL Complete and ABI/INFORM Complete. Key terms
utilized for the search were "nursing value" OR "nursing care value" OR "value of
nursing". METHODS: Caron and Bowers' (2000) dimensional analysis method was used
as a guide for the project. RESULTS: Dimensions identified from this concept
analysis included: (a) economic, (b) relational, and (c) societal. CONCLUSION:
Direct care nurses experience the relational and societal dimensions of the value
of nursing care. Patients and/or families experience the relational dimension of
value in nursing care. Health care administrators, third-party payers, and nurse
researchers interpret value from the economic dimension. Future nursing research
should better quantify the economic value of nursing care. Qualitative research
which focuses on how patients and families experience the value of nursing care
would also contribute to further refinement of this concept.
PMID- 28407261
TI - Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic
cancer: An analysis of 18 243 patients.
AB - BACKGROUND: Neoadjuvant therapy has theoretical benefits for pancreatic cancer;
however, its association with perioperative outcomes remains controversial. This
study sought to evaluate variation in use of neoadjuvant therapy and outcomes
following pancreatic resection. METHODS: The National Cancer Data Base (1998
2011) was queried for patients with Stage I or II pancreatic adenocarcinoma who
underwent pancreaticoduodenectomy. Subjects were classified by use of neoadjuvant
chemotherapy and/or radiation therapy. Factors associated with use of neoadjuvant
therapy were evaluated, and outcomes were compared. RESULTS: A 18 243 patients
were identified; 1375 (7.5%) received neoadjuvant therapy. From 1998 to 2011, use
of neoadjuvant therapy increased from 4.3% to 17.0%. Patients receiving
neoadjuvant therapy were younger (63.1 vs 66.1 years, P = 0.001) and more likely
to receive treatment at an academic facility (64.4% vs 51.4%, P < 0.001).
Patients who received neoadjuvant therapy were more likely to have negative
margins (77.8% vs 85.5%), negative lymph nodes (42.9% vs 59.3%) and tumors
confined to the pancreas (65.8% vs 70.6%, all P < 0.001). Patients receiving
neoadjuvant therapy had lower 30-day mortality (2.0% vs 4.6%, P < 0.001) and
readmission rates (7.4% vs 9.5%, P = 0.02). CONCLUSIONS: Neoadjuvant therapy use
is increasing and associated with comparable short-term outcomes. Further studies
are needed to identify patients who would benefit from neoadjuvant therapy.
PMID- 28407262
TI - Lay Worker Health Literacy: A Concept Analysis and Operational Definition.
AB - The concept of lay worker health literacy is created by concurrently analyzing
and synthesizing two intersecting concepts, lay workers and health literacy.
Articulation of this unique intersection is the result of implementing a
simplified Wilson's Concept Analysis Procedure. This process incorporates the
following components: a) selecting a concept, b) determining the aims/purposes of
analysis, c) identifying all uses of the concept, d) determining defining
attributes, e) identifying a model case, f) identifying borderline, related,
contrary, and illegitimate cases, g) identifying antecedents and consequences,
and h) defining empirical referents. Furthermore, as current literature provides
no operational definition for lay worker health literacy, one is created to
contribute cohesion to the concept.
PMID- 28407263
TI - Successful ablation of plunging ranula by ultrasound-guided percutaneous ethanol
injection.
AB - Evidence supporting any one treatment for plunging ranula is limited. Standard
treatment-complete excision of the sublingual gland and ranula-is invasive and
morbid given the close operative proximity to the submandibular duct and lingual
nerve. OK-432 (Picibanil; Chugai Pharmaceutical Co., Tokyo, Japan) sclerotherapy
has been studied as a less invasive treatment but is inaccessible in the United
States. This report illustrates the successful management of a plunging ranula
using ultrasound-guided percutaneous ethanol injection. Within 2 months of the
procedure, the patient had complete resolution of the plunging ranula, with no
associated side effects. We propose that ultrasound-guided percutaneous ethanol
injection be considered for the management of plunging ranula. Laryngoscope,
127:2239-2241, 2017.
PMID- 28407264
TI - Microvascular anastomosis simulation using a chicken thigh model: Interval versus
massed training.
AB - OBJECTIVES/HYPOTHESIS: To compare the effectiveness of massed versus interval
training when teaching otolaryngology residents microvascular suturing on a
validated microsurgical model. STUDY DESIGN: Otolaryngology residents were placed
into interval (n = 7) or massed (n = 7) training groups. The interval group
performed three separate 30-minute practice sessions separated by at least 1
week, and the massed group performed a single 90-minute practice session. Both
groups viewed a video demonstration and recorded a pretest prior to the first
training session. A post-test was administered following the last practice
session. METHODS: At an academic medical center, 14 otolaryngology residents were
assigned using stratified randomization to interval or massed training. Blinded
evaluators graded performance using a validated microvascular Objective
Structured Assessment of Technical Skill tool. The tool is comprised of two major
components: task-specific score (TSS) and global rating scale (GRS). Participants
also received pre- and poststudy surveys to compare subjective confidence in
multiple aspects of microvascular skill acquisition. RESULTS: Overall, all
residents showed increased TSS and GRS on post- versus pretest. After completion
of training, the interval group had a statistically significant increase in both
TSS and GRS, whereas the massed group's increase was not significant. Residents
in both groups reported significantly increased levels of confidence after
completion of the study. CONCLUSIONS: Self-directed learning using a chicken
thigh artery model may benefit microsurgical skills, competence, and confidence
for resident surgeons. Interval training results in significant improvement in
early development of microvascular anastomosis skills, whereas massed training
does not. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2490-2494, 2017.
PMID- 28407265
TI - OsHAC4 is critical for arsenate tolerance and regulates arsenic accumulation in
rice.
AB - Soil contamination with arsenic (As) can cause phytotoxicity and elevated As
accumulation in rice grain. Here, we used a forward genetics approach to
investigate the mechanism of arsenate (As(V)) tolerance and accumulation in rice.
A rice mutant hypersensitive to As(V), but not to As(III), was isolated. Genomic
resequencing and complementation tests were used to identify the causal gene. The
function of the gene, its expression pattern and subcellular localization were
characterized. OsHAC4 is the causal gene for the As(V)-hypersensitive phenotype.
The gene encodes a rhodanase-like protein that shows As(V) reductase activity
when expressed in Escherichia coli. OsHAC4 was highly expressed in roots and was
induced by As(V). In OsHAC4pro-GUS transgenic plants, the gene was expressed
exclusively in the root epidermis and exodermis. OsHAC4-eGFP was localized in the
cytoplasm and the nucleus. Mutation in OsHAC4 resulted in decreased As(V)
reduction in roots, decreased As(III) efflux to the external medium and markedly
increased As accumulation in rice shoots. Overexpression of OsHAC4 increased
As(V) tolerance and decreased As accumulation in rice plants. OsHAC4 is an As(V)
reductase that is critical for As(V) detoxification and for the control of As
accumulation in rice. As(V) reduction, followed by As(III) efflux, is an
important mechanism of As(V) detoxification.
PMID- 28407266
TI - Hereditary neuropathy with liability to pressure palsy in patients under 30 years
old: Neurophysiological data and proposed electrodiagnostic criteria.
AB - INTRODUCTION: In young patients with mononeuropathy who lack family history and
precipitating factors, hereditary neuropathy with liability to pressure palsy
(HNPP) may be a possibility. Our objective is to propose neurophysiological
criteria for HNPP in patients <30 years of age. METHODS: We conducted a national
multicenter retrospective clinical and neurophysiological study in patients under
30 with genetically confirmed HNPP. RESULTS: All of the 51 patients included in
the study had at least 1 demyelinating pattern in 2 asymptomatic nerves, and 3
abnormalities were found in almost 90%, including slowed motor nerve conduction
velocity across the elbow in at least 1 ulnar nerve (97.5%), increased distal
motor latency (DML) in at least 1 fibular nerve (95.8%), and increased DML in
both median nerves (89%). Age influenced DML slightly only in the fibular nerve.
DISCUSSION: Dissemination of nerve involvement in HNPP incites to perform a
complete nerve conduction study. including bilateral ulnar, fibular, and median
nerves. Muscle Nerve 57: 217-221, 2018.
PMID- 28407267
TI - Orangutans, enamel defects, and developmental health: A comparison of Borneo and
Sumatra.
AB - Orangutans (Pongo sp.) show among the highest occurrence of three types of
developmental enamel defect. Two are attributed to nutritional factors that
reduce bone growth in the infant's face early in development. Their timing and
prevalence indicate that Sumatra provides a better habitat than does Borneo. The
third type, repetitive linear enamel hypoplasia (rLEH) is very common but its
etiology is not understood. Our objective is to draw attention to this enigmatic,
episodic stressor in the lives of orangutans. We are concerned that neglect of
this possible marker of ill health may be contributing, through inaction, to
their alarming decline in numbers. Width and depth of an LEH are considered
proxies for duration and intensity of stress. The hypothesis that Bornean
orangutans would exhibit relatively wider and deeper LEH was tested on 163
independent episodes of LEH from 9 Sumatran and 26 Bornean orangutans measured
with a NanoFocus AG "usurf Mobile Plus" scanner. Non-normally distributed data
(depths) were converted to natural logs. No difference was found in width of LEH
among the two island taxa; nor are their differences in width or depth between
the sexes. After controlling for significant differences in LEH depths between
incisors and canines, defects are, contrary to prediction, significantly deeper
in Sumatran than Bornean animals (median = 28, 18 um, respectively). It is
concluded that repetitive LEH records an unknown but significant stressor present
in both Sumatra and Borneo, with an average periodicity of 6 months (or multiples
thereof) that lasts about 6-8 weeks. It is worse in Sumatra. Given this
patterning, shared with apes from a wide range of ecological and temporal
sources, rLEH is more likely attributable to disease than to malnutrition.
PMID- 28407268
TI - Cross-cultural adaptation, reliability and construct validity of the Tampa scale
for kinesiophobia for temporomandibular disorders (TSK/TMD-Br) into Brazilian
Portuguese.
AB - Fear of movement (kinesiophobia) seems to play an important role in the
development of chronic pain. However, for temporomandibular disorders (TMD),
there is a scarcity of studies about this topic. The Tampa Scale for
Kinesiophobia for TMD (TSK/TMD) is the most widely used instrument to measure
fear of movement and it is not available in Brazilian Portuguese. The purpose of
this study was to culturally adapt the TSK/TMD to Brazilian Portuguese and to
assess its psychometric properties regarding internal consistency, reliability,
and construct and structural validity. A total of 100 female patients with
chronic TMD participated in the validation process of the TSK/TMD-Br. The
intraclass correlation coefficient (ICC) was used for statistical analysis of
reliability (test-retest), Cronbach's alpha for internal consistency, Spearman's
rank correlation for construct validity and confirmatory factor analysis (CFA)
for structural validity. CFA endorsed the pre-specified model with two domains
and 12-items (Activity Avoidance - AA/Somatic Focus - SF) and all items obtained
a loading factor greater than 0.4. Acceptable levels of reliability were found
(ICC > 0.75) for all questions and domains of the TSK/TMD-Br. For internal
consistency, Cronbach's alpha of 0.78 for both domains were found. Moderate
correlations (0.40 < r < 0.60) were observed for 84% of the analyses conducted
between TSK/TMD-Br scores versus catastrophising, depression and jaw functional
limitation. TSK/TMD-Br 12 items and two-factor demonstrated sound psychometric
properties (transcultural validity, reliability, internal consistency and
structural validity). In such a way, the instrument can be used in clinical
settings and for research purposes.
PMID- 28407269
TI - Clinical, functional and inflammatory characteristics in patients with
paucigranulocytic stable asthma: Comparison with different sputum phenotypes.
AB - BACKGROUND: According to induced sputum cell count, four different asthma
phenotypes have been recognized (eosinophilic, neutrophilic, mixed and
paucigranulocytic). The aim of this study was to detect functional and
inflammatory characteristics of patients with paucigranulocytic asthma. METHODS:
A total of 240 asthmatic patients were categorized into the four phenotypes
according to cell counts in induced sputum. All patients underwent pulmonary
function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The
levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured
in sputum supernatant. Treatment, asthma control and the presence of severe
refractory asthma (SRA) were also recorded. RESULTS: Patients were categorized
into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%),
neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test
did not differ between groups (P=.288), patients with paucigranulocytic asthma
had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0
(59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic,
mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA
occurred more frequently in the eosinophilic and mixed phenotype (41.6% and
43.7%, respectively) and less frequently in the neutrophilic and
paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and
IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were
higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with
neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8%
of patients with paucigranulocytic asthma had poor asthma control. CONCLUSION:
Paucigranulocytic asthma most likely represents a "benign" asthma phenotype,
related to a good response to treatment, rather than a "true" phenotype of
asthma. However, paucigranulocytic patients that remain not well controlled
despite optimal treatment represent an asthmatic population that requires further
study for potential novel targeted interventions.
PMID- 28407270
TI - Comparison of Diagnostic Accuracy for the Low-Type Imperforate Anus Between Prone
Cross-Table Radiography and Sonography.
AB - OBJECTIVES: To compare the diagnostic accuracy for the low-type imperforate anus
between prone cross-table radiography and sonography. METHODS: We included 20
neonates with imperforate anus: 13 with a surgically proven low type and 7 with
an intermediate or high type. The distance between the distal rectal pouch and
the perineum (pouch-perineum distance) was measured by both sonography and prone
cross-table radiography. A previously established pouch-perineum distance of 10
mm was used as the cutoff for diagnosis of a low-type imperforate anus. The
fistula location was also determined with sonography. We then compared the
diagnostic accuracy of the imaging methods for a low-type imperforate anus using
the cutoff value of the pouch-perineum distance alone and both the cutoff value
of the pouch-perineum distance and fistula location. The McNemar test was used
for statistical analysis. RESULTS: With the use of only the pouch-perineum
distance, the diagnostic accuracy for the low-type imperforate anus based on
sonographic measurements was comparable with the accuracy achieved by prone cross
table radiographic measurements (60.0% [12 of 20] versus 45.0% [9 of 20]; P =
.625). With the use of the pouch-perineum distance and fistula location, the
diagnostic accuracy of sonography was significantly better than the accuracy of
prone cross-table radiography (90.0% [18 of 20] versus 45% [9 of 20]; P = .012).
CONCLUSIONS: The diagnostic accuracy of sonography for the low-type imperforate
anus based on both the pouch-perineum distance and fistula location is better
than that of prone cross-table radiography. If the pouch-perineum distance on
prone cross-table radiography is greater than 10 mm, a sonographic examination to
determine the fistula location could be recommended.
PMID- 28407272
TI - The relative effects of reproductive condition, stress, and seasonality on
patterns of parasitism in wild female black howler monkeys (Alouatta pigra).
AB - Parasitic infections in wildlife are shaped by host-related traits including
individual reproductive condition. It has been argued that female primates are
more susceptible to infectious diseases during pregnancy due to short-term
changes in immune function that result in reduced ability to combat infections.
Likewise, lactation, which is the most energetically expensive state, may affect
immunity and infection risk due to tradeoffs between milk production and
maintenance of immune function. Here, we examine the degree to which parasite
prevalence and parasite richness are affected by female reproductive condition
and stress levels in wild female black howler monkeys (Alouatta pigra). Over the
course of one year, we collected fresh fecal samples from 15 adult females
belonging to seven black howler groups living in Escarcega, Mexico. Fecal samples
were used for parasitological analysis and for measuring fecal glucocorticoid
metabolites (i.e., stress biomarker). We found that the prevalence of intestinal
parasites and parasite richness did not differ among non-pregnant, pregnant, and
lactating females. Fecal glucocorticoid metabolite levels increased significantly
during pregnancy and during the first month of lactation, and positively
predicted the probability of Controrchis biliophilus infection. Parasite
prevalence and richness decreased during the months of increased rainfall. We
conclude that reproductive physiology has limited consequences on intestinal
parasitic infection risk in female black howler monkeys and that seasonal
environmental fluctuations have greater effects.
PMID- 28407271
TI - A potent hepatitis B surface antigen response in subjects with inactive hepatitis
B surface antigen carrier treated with pegylated-interferon alpha.
AB - : Hepatitis B surface antigen (HBsAg) clearance represents a clinical cure,
although the clearance rate is extremely low. The aim of this study was to
evaluate the feasibility and safety profiles of pegylated-interferon alpha-2a
(PEG-IFNalpha-2a) as a therapeutic option for inactive HBsAg carriers. There were
144 inactive HBsAg carriers enrolled and divided into a therapeutic group (102
subjects) and a control group (42 subjects). PEG-IFNalpha-2a and PEG-IFNalpha-2a
combined with adefovir dipivoxil were used for treatment group subjects with
hepatitis B virus DNA <20 IU/mL and 20 IU/mL <= hepatitis B virus DNA < 2,000
IU/mL, respectively. Total therapy duration was no more than 96 weeks. HBsAg
clearance and seroconversion rates at therapeutic weeks 48 and 96 were used to
evaluate the therapeutic efficacy. Per protocol analysis showed that the HBsAg
clearance rate and seroconversion rate in the treatment group were 29.8% and
20.2% at week 48 and increased to 44.7% and 38.3% at week 96, respectively.
However, the HBsAg clearance rate in the control group was 2.4% at weeks 48 and
96, and no subject achieved seroconversion. The quantitative HBsAg levels and
changes during the early period of treatment (at week 12 and week 24) as well as
the alanine aminotransferase elevation at week 12 were strong predictors of HBsAg
clearance. The adverse events were similar to those with treatment for chronic
hepatitis B patients. CONCLUSION: High rates of HBsAg clearance and
seroconversion could be achieved by PEG-IFNalpha-2a-based treatments and the
treatments were relatively safe for inactive HBsAg carriers. (Hepatology
2017;66:1058-1066).
PMID- 28407273
TI - Comorbidity of chronic spontaneous urticaria and autoimmune thyroid diseases: A
systematic review.
AB - Patients with chronic spontaneous urticaria (CSU) are widely held to often have
other autoimmune disorders, including autoimmune thyroid disease. Here, we
systematically evaluated the literature on the prevalence of thyroid autoimmunity
in CSU and vice versa. There is a strong link between CSU and elevated levels of
IgG antithyroid autoantibodies (AAbs), with most of a large number of studies
reporting rates of >=10%. Levels of IgG against thyroid peroxidase (TPO) are more
often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence).
Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU
than in children (strong evidence). Patients with CSU exhibit significantly
higher levels of IgG antithyroid AAbs (strong evidence) and IgE-anti-TPO (weak
evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the
use of glucocorticoids (weak evidence) but not to disease duration or
severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid
dysfunction rates are increased in patients with CSU (strong evidence).
Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism
and Graves' disease (strong evidence). Thyroid dysfunction is more common in
adult patients with CSU than in children (strong evidence) and in female than in
male patients with CSU (weak evidence). Urticaria including CSU is more prevalent
in patients with thyroid autoimmunity than in controls (weak evidence). CSU can
improve in response to treatment with levothyroxine or other thyroid drugs
(strong evidence). Pathogenic mechanisms in CSU patients with thyroid
autoimmunity may include IgE against autoantigens, immune complexes, and
complement.
PMID- 28407274
TI - The Riddle of Juvenile Sclerosing Cholangitis.
PMID- 28407275
TI - Agriculturally important microbial biofilms: Present status and future prospects.
AB - Microbial biofilms are a fascinating subject, due to their significant roles in
the environment, industry, and health. Advances in biochemical and molecular
techniques have helped in enhancing our understanding of biofilm structure and
development. In the past, research on biofilms primarily focussed on health and
industrial sectors; however, lately, biofilms in agriculture are gaining
attention due to their immense potential in crop production, protection, and
improvement. Biofilms play an important role in colonization of surfaces - soil,
roots, or shoots of plants and enable proliferation in the desired niche, besides
enhancing soil fertility. Although reports are available on microbial biofilms in
general; scanty information is published on biofilm formation by agriculturally
important microorganisms (bacteria, fungi, bacterial-fungal) and their
interactions in the ecosystem. Better understanding of agriculturally important
bacterial-fungal communities and their interactions can have several implications
on climate change, soil quality, plant nutrition, plant protection,
bioremediation, etc. Understanding the factors and genes involved in biofilm
formation will help to develop more effective strategies for sustainable and
environment-friendly agriculture. The present review brings together fundamental
aspects of biofilms, in relation to their formation, regulatory mechanisms, genes
involved, and their application in different fields, with special emphasis on
agriculturally important microbial biofilms.
PMID- 28407276
TI - Synthesis, Characterization, and Biological Evaluation of Some Novel Quinoxaline
Derivatives as Antiviral Agents.
AB - Ethyl (6,7-dimethyl-2-oxo-3,4-dihydroquinoxalin-3-yl)acetate and ethyl (6-methyl
2-oxo-3,4-dihydroquinoxalin-3-yl)acetate (1a,b), 3-methylquinoxalin-2(1H)-one (4)
and 1,4-dihydroquinoxaline-2,3-dione (11) were the starting precursors for nine
novel quinoxaline compounds, 3a, 6, 10, 13, 15, 16, 17, 18, and 20, via adopting
different nucleophilic reactions. The synthesized compounds were tested for their
antiviral activity against HCV, HBV, HSV-1, and HCMV. Concomitantly, their safety
profile was investigated as well as their selectivity against the viral strains.
The Virology Unit at the University of Alabama recorded that two compounds, i.e.,
1a and 20, exhibited highly potent activity against HCMV with lower IC50 values
(<0.05 MUM) compared to ganciclovir (IC50 = 0.59 MUM). Compounds 1a and 20 also
exhibited low cytotoxicity together with a high selectivity index.
PMID- 28407277
TI - Recurrence of Thrombin-Injected Pseudoaneurysms Under Ultrasound Guidance: A 10
Year Retrospective Analysis.
AB - OBJECTIVES: Ultrasound-guided thrombin injection has become standard treatment
for extremity pseudoaneurysms. Our specific aims were to determine the procedural
success rate, the procedural complication rate, and the factors associated with
pseudoaneurysm recurrence. METHODS: A total of 262 consecutive cases of
ultrasound-guided thrombin repair of pseudoaneurysms were identified between
January 1, 2006, and March 20, 2016. The procedural and follow-up ultrasound
studies were reviewed. Outcomes of interest included procedural success (defined
as complete thrombosis at the time of injection and on a follow-up examination),
incomplete pseudoaneurysm thrombosis, and postprocedural recurrence.
Postprocedural pseudoaneurysm recurrences were compared to procedural successes
with regard to patient demographics, pseudoaneurysm characteristics, amount of
thrombin injected, and periprocedural laboratory values. RESULTS: Procedural
success occurred in 85.7% of cases. Complications occurred in 3.0% of cases. The
mean patient age +/- SD was 72.3 +/- 11.3 years. The median amount of thrombin
injected was 500 U (interquartile range, 400 U). The median follow-up time was 1
day (interquartile range, 0 days). A pseudoaneurysm size of 2 cm or larger and
thrombocytopenia were significant independent predictors of pseudoaneurysm
recurrence (P = .003 and .03, respectively). The odds ratios for pseudoaneurysm
recurrence were 2.29 for pseudoaneurysm size of 2 cm or larger (P = .03) and 1.04
for thrombocytopenia (P = .04). CONCLUSIONS: Thrombin injection of
pseudoaneurysms is an off-label procedure with few complications and a high
success rate. Follow-up imaging is recommended in all pseudoaneurysms that are 2
cm or larger and in patients with thrombocytopenia.
PMID- 28407278
TI - Prevention and treatment of complications of selective internal radiation
therapy: Expert guidance and systematic review.
AB - Selective internal radiation therapy (or radioembolization) by intra-arterial
injection of radioactive yttrium-90-loaded microspheres is increasingly used for
the treatment of patients with liver metastases or primary liver cancer. The high
dose beta-radiation penetrates an average of only 2.5 mm from the source, thus
limiting its effects to the site of delivery. However, the off-target diversion
of yttrium-90 microspheres to tissues other than the tumor may lead to
complications. The most prominent of these complications include radiation
gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and
radioembolization-induced liver disease, which may occur despite careful
pretreatment planning. Thus, selective internal radiation therapy demands an
expert multidisciplinary team approach in order to provide comprehensive care for
patients. This review provides recommendations to multidisciplinary teams on the
optimal medical processes in order to ensure the safe delivery of selective
internal radiation therapy. Based on the best available published evidence and
expert opinion, we recommend the most appropriate strategies for the prevention,
early diagnosis, and management of potential radiation injury to the liver and to
other organs. (Hepatology 2017;66:969-982).
PMID- 28407279
TI - Orangutan trade, confiscations, and lack of prosecutions in Indonesia.
AB - Prosecuting and sentencing law breakers punishes the offender and acts as a
deterrent for future law breakers. With thousands of Sumatran and Bornean
orangutans (Pongo abelii and P. pygmaeus) having entered private and government
rescue centers and facilities, I evaluate the role of successful prosecution in
orangutan conservation in Indonesia. Orangutans have been protected in Indonesian
since 1931 and they are not allowed to be traded or to be kept as pets. In the
period 1993-2016 at least 440 orangutans were formally confiscated, and many more
were "donated" to law enforcement agencies. This resulted in seven (7) successful
prosecutions by six different courts. Sentencing was lenient (median fine US$ 442
out of a possible US$ 7,600, median prison sentence 8 months out of a possible 5
years) and certainly too low to act as a deterrent. A paradigm shift within
government authorities, conservation organizations, the judiciary, and by the
general public is needed where trade in orangutans is no longer seen as a crime
against an individual animal but as an economic crime that negatively affects
society as a whole. Prosecuting offenders for tax evasion, corruption,
endangering public health, animal cruelty, and smuggling, in addition to
violating protected species laws, would allow for an increase in sentencing,
resulting in a stronger deterrent, and greater public support. Conservation and
welfare NGOs have a duty to become more proactive in a drive to increase
enforcement; rescuing orangutans always has to coincide with prosecuting
offenders and failures, and successes of these prosecutions have to be vigorously
publicized. Despite numerous commitments made by Indonesia to orangutan
conservation, and clear failures to deliver on almost all components,
international donors have increased their funding year on year; it is time that
this changes to a system where not failure is rewarded but success.
PMID- 28407280
TI - Coil-assisted retrograde transvenous obliteration and partial splenic artery
embolization for hepatic encephalopathy.
PMID- 28407281
TI - Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney
Disease.
AB - OBJECTIVES: To evaluate the value of multiparametric quantitative ultrasound
imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic
findings as reference standards. METHODS: We prospectively measured
multiparametric quantitative ultrasound markers with grayscale, spectral Doppler,
and acoustic radiation force impulse imaging in 25 patients with CKD before
kidney biopsy and 10 healthy volunteers. Based on all pathologic
(glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and
edema) scores, the patients with CKD were classified into mild (no grade 3 and <2
of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD
groups. Multiparametric quantitative ultrasound parameters included kidney
length, cortical thickness, pixel intensity, parenchymal shear wave velocity,
intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and
resistive index. We tested the difference in quantitative ultrasound parameters
among mild CKD, moderate to severe CKD, and healthy controls using analysis of
variance, analyzed correlations of quantitative ultrasound parameters with
pathologic scores and the estimated glomerular filtration rate (GFR) using
Pearson correlation coefficients, and examined the diagnostic performance of
quantitative ultrasound parameters in determining moderate CKD and an estimated
GFR of less than 60 mL/min/1.73 m2 using receiver operating characteristic curve
analysis. RESULTS: There were significant differences in cortical thickness,
pixel intensity, PSV, and EDV among the 3 groups (all P < .01). Among
quantitative ultrasound parameters, the top areas under the receiver operating
characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for
determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated
GFR of less than 60 mL/min/1.73 m2 . Moderate to good correlations were found for
PSV, EDV, and pixel intensity with pathologic scores and estimated GFR.
CONCLUSIONS: The PSV, EDV, and pixel intensity are valuable in determining
moderate to severe CKD. The value of shear wave velocity in assessing CKD needs
further investigation.
PMID- 28407282
TI - Vector competence and innate immune responses to dengue virus infection in
selected laboratory and field-collected Stegomyia aegypti (= Aedes aegypti).
AB - Control of dengue virus (DenV) transmission, primarily based on strategies to
reduce populations of the principle vector Stegomya aegypti (= Aedes aegypti)
(Diptera: Culicidae), is difficult to sustain over time. Other potential
strategies aim to manipulate characteristics such as vector competence (VC), the
innate capacity of the vector to transmit the virus. Previous studies have
identified genetic factors, including differential expression of apoptosis
related genes, associated with the refractory and susceptible phenotypes in
selected strains of S. aegypti from Cali, Colombia. The present study was
designed to evaluate the variability of VC in selected strains against different
DenV serotypes and to determine whether field-collected mosquitoes respond
similarly to selected laboratory strains in terms of enhanced or reduced
expression of apoptosis-related genes. Vector competence differed between
strains, but did not differ in response to different DenV serotypes. Differences
in VC were observed among mosquitoes collected from different localities in Cali.
The overexpression of the pro-apoptosis genes, caspase 16 and Aedronc, was
conserved in field-collected refractory mosquitoes and the selected laboratory
refractory strain. The results suggest that the apoptosis response is conserved
among all refractory mosquitoes to inhibit the development of all DenV serotypes.
PMID- 28407283
TI - Acoustic Radiation Force Impulse Imaging for Assessing Liver Fibrosis
Preoperatively in Infants With Biliary Atresia: Comparison With Liver Fibrosis
Biopsy Pathology.
AB - OBJECTIVES: The purpose of this study was to investigate the diagnostic
performance of acoustic radiation force impulse (ARFI) in assessing liver
fibrosis preoperatively in infants with biliary atresia (BA). METHODS: A total of
50 consecutive infants with BA and 50 healthy infants who underwent ARFI
examination were recruited. Siemens Acuson S2000 in Virtual Touch Quantification
mode (Siemens Medical Solutions, Mountain View, CA) was used to measure shear
wave speeds (SWSs). All infants with BA underwent a liver biopsy within 3 days
after ARFI imaging. The liver fibrosis stages of specimens were defined according
to the Batts-Ludwig scoring system. The correlation analysis was performed
between SWSs and pathological findings. Cut-off values were determined using
receiver operating characteristic (ROC) curves. RESULTS: The mean SWS in the BA
group was significantly higher than controls (mean +/- standard deviation): 1.89
+/- 0.45 versus 1.12 +/- 0.06 m/s; P < .001). A significant correlation was found
between the SWSs and fibrosis stages (r = 0.719, P < .001). The cut-off value for
predicting significant fibrosis (F >= 2), severe fibrosis (F >= 3), and cirrhosis
(F = 4) was 1.53, 1.80 and 2.16 m/s, respectively, and the area under the ROC
curve was 0.823, 0.884 and 0.917, respectively. CONCLUSIONS: Acoustic radiation
force impulse imaging showed significant correlation with the severity of liver
fibrosis by comparing it with liver fibrosis biopsy pathology. It may be an
effective method for liver fibrosis assessment, prognosis prediction, and
clinical management in infants with BA.
PMID- 28407284
TI - Executive functions in adolescents with binge-eating disorder and obesity.
AB - OBJECTIVE: Binge-eating disorder (BED) in adults is associated with alterations
in executive functions (EF) and obesity. Much less is known about these
relationships in adolescents, including whether poor EF are associated with
eating disorder psychopathology and/or elevated body mass index. This study
examined EF in response to neutral stimuli in youth with BED. METHOD: Adolescents
with BED and obesity (n = 22), individually matched adolescents with obesity (n =
22), and normal weight (n = 22) completed neuropsychological tests targeting
inhibition (Color-Word Interference Test), sustained attention (D2 Concentration
Endurance Test), cognitive flexibility (Comprehensive Trail Making Test), and
decision-making (Iowa Gambling Task). RESULTS: Adolescents with BED and obesity
displayed significantly poorer inhibitory control compared to normal-weight
adolescents. This effect persisted after controlling for the level of secondary
education. However, initial differences between adolescents with obesity and
normal-weight controls regarding inhibitory control and sustained attention
vanished after controlling for education. The three groups did not differ
regarding cognitive flexibility and decision-making. Moreover, adolescents with
BED and obesity did not perform worse than adolescents with obesity on any of the
neuropsychological tests. DISCUSSION: Overall, our results indicate that
adolescent BED is associated with only a few alterations in general EF,
specifically inhibitory control, and underline BED and educational level as
confounding factors in neuropsychological research on obesity. To further
delineate EF profiles of adolescents with BED, future research should focus on EF
in response to disorder-related stimuli and experimental settings with high
ecological validity.
PMID- 28407285
TI - Spatial variation in bacterial community in natural wetland-river-sea ecosystems.
AB - Wetland-estuarine-marine environments are typical oxic/anoxic transition zones
and have complex water flow-paths within the zone of mixing where freshwater
interacts with ocean water. Little is known about the impact of this interaction
on bacterial community structures or the relationship between bacterial community
and geochemical factors in such transitional mixing environments. Hence, we
investigated the distribution patterns and diversity in bacterial communities in
the Yellow River estuary-coastal wetland-Bohai Sea transition zone by analyzing
39 samples from 13 ordered sites. High-throughput sequencing of the 16S rRNA gene
revealed significant shifts in diversity and distribution of bacterial community
in sediments from the Yellow River estuary to the Bohai Sea. Yellow River
sediment was dominated by hydrogen-, nitrogen-, and iron-cycling bacteria, such
as Hydrogenophaga, Nitrospira, Pseudomonas, and Thiobacillus. The coastal wetland
had a haloduric community associated with different functions, such as
Planctomyces, Marinobacter, Halomonas, Salinivibrio, and Salinibacter. The Bohai
Sea sediment had a higher relative abundance of Lutimonas, Desulfococcus,
Photobacterium, Propionigenium, and Vibrio. Spatial variation in bacterial
community was correlated with pH, salinity and sulfate (SO42-) concentration in
such coastal environments. The major bacterial taxa were significantly different
across the wetland, estuary, and coastal marine ecosystems, indicating
substantial spatial heterogeneity among the three ecosystems. Statistical
analysis revealed strong links between variation in bacterial community structure
and ecosystem type. Our results demonstrate the importance of geographic and
geochemical factors in structuring the bacterial community in natural
environments.
PMID- 28407286
TI - PET imaging with copper-64 as a tool for real-time in vivo investigations of the
necessity for cross-linking of polymeric micelles in nanomedicine.
AB - Polymeric micelles in nanomedicine are often cross-linked to prevent
disintegration in vivo. This typically requires clinically problematic chemicals
or laborious procedures. In addition, cross-linking may interfere with advanced
release strategies. Despite this, it is often not investigated whether cross
linking is necessary for efficient drug delivery. We used positron emission
tomography (PET) imaging with 64 Cu to demonstrate general methodology for real
time in vivo investigations of micelle stability. Triblock copolymers with 4
methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the
handle region (PHEMA) with CB-TE2A chelators. Polymeric micelles were formed by
dialysis and one half was core cross-linked (CL) by UV light and the other half
was not (nonCL). Both CL and nonCL were radiolabeled with 64 Cu and compared in
vivo in tumor-bearing mice, with free 64 Cu as control. Accumulation in relevant
organs was quantified by region of interest analysis on PET images and ex vivo
counting. It was observed that CL and nonCL showed limited differences in
biodistribution from each other, whereas both differed markedly from control
(free 64 Cu). This demonstrated that 4-methylcoumarin core micelles may form
micelles that are stable in circulation even without cross-linking. The
methodology presented here where individual unimers are radiolabeled is
applicable to a wide range of polymeric micelle types.
PMID- 28407287
TI - Reproducibility of three dimensional digital preoperative planning for the
osteosynthesis of distal radius fractures.
AB - A three-dimensional (3D) digital preoperative planning system for the
osteosynthesis of distal radius fractures was developed for clinical practice. To
assess the usefulness of the 3D planning for osteosynthesis, we evaluated the
reproducibility of the reduction shapes and selected implants in the patients
with distal radius fractures. Twenty wrists of 20 distal radius fracture patients
who underwent osteosynthesis using volar locking plates were evaluated. The 3D
preoperative planning was performed prior to each surgery. Four surgeons
conducted the surgeries. The surgeons performed the reduction and the placement
of the plate while comparing images between the preoperative plan and
fluoroscopy. Preoperative planning and postoperative reductions were compared by
measuring volar tilt and radial inclination of the 3D images. Intra-class
correlation coefficients (ICCs) of the volar tilt and radial inclination were
evaluated. For the implant choices, the ICCs for the screw lengths between the
preoperative plan and the actual choices were evaluated. The ICCs were 0.644 (p <
0.01) and 0.625 (p < 0.01) for the volar tilt and radial inclination in the 3D
measurements, respectively. The planned size of plate was used in all of the
patients. The ICC for the screw length between preoperative planning and actual
choice was 0.860 (p < 0.01). Good reproducibility for the reduction shape and
excellent reproducibility for the implant choices were achieved using 3D
preoperative planning for distal radius fracture. Three-dimensional digital
planning was useful to visualize the reduction process and choose a proper
implant for distal radius fractures. (c) 2017 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 35:2646-2651, 2017.
PMID- 28407288
TI - Efficient replication of blood-borne hepatitis C virus in human fetal liver stem
cells.
AB - : The development of pathogenic mechanisms, specific antiviral treatments and
preventive vaccines for hepatitis C virus (HCV) infection has been limited due to
lack of cell culture models that can naturally imitate the entire HCV life cycle.
Here, we established an HCV cell culture model based on human fetal liver stem
cells (hFLSCs) that supports the entire blood-borne hepatitis C virus (bbHCV)
life cycle. More than 90% of cells remained infected by various genotypes. bbHCV
was efficiently propagated, and progeny virus were infectious to hFLSCs. The
virus could be passed efficiently between cells. The viral infectivity was
partially blocked by specific antibodies or small interfering RNA against HCV
entry factors, whereas HCV replication was inhibited by antiviral drugs. We
observed viral particles of approximately 55 nm in diameter in both cell culture
media and infected cells after bbHCV infection. CONCLUSION: Our data show that
the entire bbHCV life cycle could be naturally imitated in hFLSCs. This model is
expected to provide a powerful tool for exploring the process and the mechanism
of bbHCV infection at the cellular level and for evaluating the treatment and
preventive strategies of bbHCV infection. (Hepatology 2017;66:1045-1057).
PMID- 28407289
TI - Dual Role of the Extracellular Domain of Human Mucin MUC1 in Metastasis.
AB - Human mucin MUC1 plays an important role in cancer development. The increased
level of this molecule expression during cancer cell progression induces
metastasis and is associated with poor prognosis for patients. There is a large
body of experimental data on the role of various functional domains of human
mucin MUC1 in metastasis. While, the cytoplasmic domain determined to play a
definitive role, the influence of extracellular domain on cancer cell
invasiveness still remains unclear. The present paper reveals that the
extracellular domain of MUC1 molecule consists of two functional subdomains-the
region of tandem repeats (TR) and the region of irregular repeats (IR). We
demonstrate the ability of each of these subdomains to alter the invasiveness of
cancer cells. The presence of the MUC1 molecules containing TR subdomain (MUC1
TR) on the surface of low-invasive cancer cells leads to the increase in their
transendothelial migration potency, while the addition of the IR subdomain to the
MUC1-TR molecule (MUC1-IR-TR) restores their natural low invasiveness. J. Cell.
Biochem. 118: 4002-4011, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407290
TI - A highly efficient method for extracting next-generation sequencing quality RNA
from adipose tissue of recalcitrant animal species.
AB - The next-generation sequencing (NGS) based RNA sequencing (RNA-Seq) and
transcriptome profiling offers an opportunity to unveil complex biological
processes. Successful RNA-Seq and transcriptome profiling requires a large amount
of high-quality RNA. However, NGS-quality RNA isolation is extremely difficult
from recalcitrant adipose tissue (AT) with high lipid content and low cell
numbers. Further, the amount and biochemical composition of AT lipid varies
depending upon the animal species which can pose different degree of resistance
to RNA extraction. Currently available approaches may work effectively in one
species but can be almost unproductive in another species. Herein, we report a
two step protocol for the extraction of NGS quality RNA from AT across a broad
range of animal species.
PMID- 28407291
TI - Use of contrast media in computed tomography and magnetic resonance imaging in
horses: Techniques, adverse events and opportunities.
AB - The use of contrast media in computed tomography (CT) and magnetic resonance
imaging (MRI) is increasing in horses. These contrast-enhanced imaging techniques
provide improved tissue delineation and evaluation, thereby expanding diagnostic
capabilities. While generally considered safe, not all contrast media exhibit the
same safety profiles. The safety of contrast media use and descriptions of
adverse events occurring in horses are sparsely reported. This review summarises
the reported evidence of contrast media use and adverse events that occur in
horses, with added contribution from other veterinary species and studies in man
for comparison. This comprehensive data set empowers equine clinicians to develop
use and monitoring strategies when working with contrast media. Finally, it
summarises the current state-of-the-art and highlights the potential applications
of contrast-enhanced CT and MRI for assessment of diseased or injured equine
tissues, as well as (patho)physiological processes.
PMID- 28407292
TI - Internalized stigma in psoriasis: A multicenter study.
AB - Internalized stigma is the adoption of negative attitudes and stereotypes of the
society regarding a person's illness. It causes decreased self-esteem and life
satisfaction, increased depression and suicidality, and difficulty in coping with
the illness. The primary aim of this study was to investigate the internalized
stigma state of psoriatic patients and to identify the factors influencing
internalized stigma. The secondary aim was to identify the correlation of
internalized stigma with quality of life and perceived health status. This
multicentre, cross-sectional study comprised 1485 patients. There was a
significant positive correlation between mean values of Psoriasis Internalized
Stigma Scale (PISS) and Psoriasis Area and Severity Index, Body Surface Area,
Dermatological Life Quality Index and General Health Questionnaire-12 (P < 0.001
in all). Lower percieved health score (P = 0.001), early onset psoriasis (P =
0.016), family history of psoriasis (P = 0.0034), being illiterate (P < 0.001)
and lower income level (P < 0.001) were determinants of high PISS scores. Mean
PISS values were higher in erythrodermic and generalized pustular psoriasis.
Involvement of scalp, face, hand, genitalia and finger nails as well as
arthropathic and inverse psoriasis were also related to significantly higher PISS
scores (P = 0.001). Our findings imply that psoriatic patients experience high
levels of internalized stigma which are associated with psoriasis severity,
involvement of visible body parts, genital area, folds or joints, poorer quality
of life, negative perceptions of general health and psychological illnesses.
Therefore, internalized stigma may be one of the major factors responsible from
psychosocial burden of the disease.
PMID- 28407293
TI - Anti-tumor effects of crocetin and related molecular targets.
AB - Natural products have gained a wide popularity as chemopreventive and anti-cancer
agents owing to their multi-mechanistic mode of action, availability and
synergism with several conventional chemotherapeutic agents. Crocetin is a
carotenoid compound isolated from the stigma of Crocus sativus L. (saffron).
Crocetin has shown promising effects as an anti-tumor agent in animal models and
cell culture systems. Crocetin retards the growth of cancer cells via inhibiting
nucleic acid synthesis, enhancing anti-oxidative system, and inducing apoptosis
and differentiation pathways. The present review outlines natural sources of
crocetin, and its pharmacokinetic and pharmacological properties relevant to the
prevention and treatment of cancer. Also, we discuss molecular targets underlying
the putative anti-tumor effects of crocetin.
PMID- 28407294
TI - Altered TERT promoter and other genomic regulatory elements: occurrence and
impact.
AB - Study of genetic alterations, inherited or acquired, that increase the risk or
drive cancers and many other diseases had remained mostly confined to coding
sequences of the human genome. Data from genome wide associations studies,
development of the Encyclopedia of DNA Elements (ENCODE), and a spurt in
detection of driver somatic mutations have shifted focus towards noncoding
regions of the human genome. The majority of genetic variants robustly associated
with cancers and other syndromes identified through genome wide studies are
located within noncoding regulatory regions of the genome. Genome wide techniques
have put an emphasis on the role of three-dimensional chromosomal structures and
cis-acting elements in regulations of different genes. The variants within
noncoding genomic regions can potentially alter a number of regulatory elements
including promoters, enhancers, insulators, noncoding long RNAs and others that
affect cancers and various diseases through altered expression of critical genes.
With effect of genetic alterations within regulatory elements dependent on other
partner molecules like transcription factors and histone marks, an understanding
of such modifications can potentially identify extended therapeutic targets. That
concept has been augmented by the detection of driver somatic noncoding mutations
within the promoter region of the telomerase reverse transcriptase (TERT) gene in
different cancers. The acquired somatic noncoding mutations within different
regulatory elements are now being reported in different cancers with an increased
regularity. In this review we discuss the occurrence and impact of germline and
somatic alterations within the TERT promoter and other genomic regulatory
elements.
PMID- 28407295
TI - Subsequent transepidermal migration of two temporary cardiac pacing wires.
PMID- 28407296
TI - Time to and predictors of dual incontinence in older nursing home admissions.
AB - AIMS: There are few studies of nursing home residents that have investigated the
development of dual incontinence, perhaps the most severe type of incontinence as
both urinary and fecal incontinence occur. To determine the time to and
predictors of dual incontinence in older nursing home residents. METHODS: Using a
cohort design, records of older nursing home admissions who were continent or had
only urinary or only fecal incontinence (n = 39,181) were followed forward for
report of dual incontinence. Four national US datasets containing potential
predictors at multiple levels describing characteristics of nursing home
residents, nursing homes (n = 445), and socioeconomic and sociodemographic status
of the community surrounding nursing homes were analyzed. A Cox proportional
hazard regression with nursing home-specific random effect was used. RESULTS: At
6 months after admission, 28% of nursing home residents developed dual
incontinence, at 1 year 42% did so, and at 2 years, 61% had dual incontinence.
Significant predictors for time to developing dual incontinence were having
urinary incontinence, greater functional or cognitive deficits, more
comorbidities, older age, and lesser quality of nursing home care. CONCLUSIONS:
The development of dual incontinence is a major problem among nursing home
residents. Predictors in this study offer guidance in developing interventions to
prevent and reduce the time to developing this problem which may improve the
quality of life of nursing residents.
PMID- 28407297
TI - Short-term complications associated with the use of transvaginal mesh in pelvic
floor reconstructive surgery: Results from a multi-institutional prospectively
maintained dataset.
AB - AIMS: Vaginal reconstructive surgery can be performed with or without mesh. We
sought to determine comparative rates of perioperative complications of native
tissue versus vaginal mesh repairs for pelvic organ prolapse. METHODS: Using the
National Surgical Quality Improvement Program (NSQIP) database, we concatenated
surgical data from vaginal procedures for prolapse repair, including anterior and
posterior colporrhaphy, paravaginal defect repair, enterocele repair, and vaginal
colpopexy using Current Procedural Terminology (CPT) coding. We stratified this
data by the modifier associated with mesh usage at the time of the procedure. We
then compared 30-day perioperative outcomes, postoperative complications
(bleeding, infection, etc), and readmission rates between women with and without
mesh-based repairs. RESULTS: We identified 10 657 vaginal reconstructive
procedures without mesh and 959 mesh-based repairs from 2009 through 2013.
Patients undergoing mesh repair were more likely to experience at least one
complication than native tissue repair (9.28% vs 6.15%, P < 0.001), with the
overall complication rate also being higher in the mesh group (11.37% vs 9.39%, P
= 0.03). Procedures with mesh had a higher rate of perioperative bleeding
requiring transfusion than native tissue repair (2.3% vs 0.49%, P < 0.001), and
organ surgical site infection (SSI) (0.52% vs 0.17%, P = 0.02). There were no
significant differences in rates of readmission, superficial, or deep SSIs,
pneumonia, urinary tract infection, sepsis, or renal failure. CONCLUSIONS: The
use of vaginal mesh for pelvic organ prolapse repair appears to result in a
higher rate of perioperative complications than native tissue repair. Patients
undergoing these procedures should be counselled preoperatively concerning these
risks.
PMID- 28407299
TI - Effects of Ultraviolet Radiation on Glioma: Systematic Review.
AB - Glioblastoma multiforme is the most aggressive primary brain tumor. Treatment is
largely palliative, with current strategies unable to prevent inevitable tumor
recurrence. Implantable micro-electromechanical systems are becoming more
feasible for the management of several human diseases. These systems may have a
role in detecting tumor recurrence and delivering localized therapies. One
potential therapeutic tool is ultraviolet (UV) light. This systematic review
assesses the effects of UV light on glioma cells. A total of 47 publications are
included. The large majority were in vitro experiments conducted on human
glioblastoma cell lines in monolayer. In these cells, UV light was shown to
induce apoptosis and the expression of genes or activation of proteins that
modulate cell death, repair, and proliferation. The nature and magnitude of
cellular response varied by UV wavelength, dose, cell line, and time after
irradiation. UVC (wavelength 100-280 nm) was most effective at inducing
apoptosis, and this effect was dose dependent. The included studies had varied
methodologies, complicating reconciliation of results. Further work will be
required to determine the best regime of UV irradiation for therapeutic use. J.
Cell. Biochem. 118: 4063-4071, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407298
TI - Spatial Differences in the Distribution of Bone Between Femoral Neck and
Trochanteric Fractures.
AB - There is little knowledge about the spatial distribution differences in
volumetric bone mineral density and cortical bone structure at the proximal femur
between femoral neck fractures and trochanteric fractures. In this case-control
study, a total of 93 women with fragility hip fractures, 72 with femoral neck
fractures (mean +/- SD age: 70.6 +/- 12.7 years) and 21 with trochanteric
fractures (75.6 +/- 9.3 years), and 50 control subjects (63.7 +/- 7.0 years) were
included for the comparisons. Differences in the spatial distributions of
volumetric bone mineral density, cortical bone thickness, cortical volumetric
bone mineral density, and volumetric bone mineral density in a layer adjacent to
the endosteal surface were investigated using voxel-based morphometry (VBM) and
surface-based statistical parametric mapping (SPM). We compared these spatial
distributions between controls and both types of fracture, and between the two
types of fracture. Using VBM, we found spatially heterogeneous volumetric bone
mineral density differences between control subjects and subjects with hip
fracture that varied by fracture type. Interestingly, femoral neck fracture
subjects, but not subjects with trochanteric fracture, showed significantly lower
volumetric bone mineral density in the superior aspect of the femoral neck
compared with controls. Using surface-based SPM, we found that compared with
controls, both fracture types showed thinner cortices in regions in agreement
with the type of fracture. Most outcomes of cortical and endocortical volumetric
bone mineral density comparisons were consistent with VBM results. Our results
suggest: 1) that the spatial distribution of trabecular volumetric bone mineral
density might play a significant role in hip fracture; 2) that focal cortical
bone thinning might be more relevant in femoral neck fractures; and 3) that areas
of reduced cortical and endocortical volumetric bone mineral density might be
more relevant for trochanteric fractures in Chinese women. (c) 2017 American
Society for Bone and Mineral Research.
PMID- 28407300
TI - Thrombin Induces CCL2 Expression in Human Lung Fibroblasts via p300 Mediated
Histone Acetylation and NF-KappaB Activation.
AB - Thrombin has been shown to play a key role in lung diseases such as pulmonary
fibrosis via the induction of fibrotic cytokine- chemokine (CC motif) ligand-2
(CCL2) expression. We previously reported that transcription factor nuclear
factor-kappaB (NF-kappaB) is responsible for thrombin-induced CCL2 expression in
human lung fibroblasts (HLFs). Here, we extended our study to investigate the
epigenetic regulation mechanism for thrombin-induced CCL2 expression in HLFs.
HLFs were cultured in F-12 medium. CCL2 protein and mRNA levels were detected by
ELISA and quantitative real-time PCR, respectively. Histone, histone
acetyltransferases, and NF-kappaB binding to CCL2 promoter were detected by ChIP
assay. NF-kappaB activation was detected by Western blotting. We revealed that
increased binding of histone acetyltransferase p300 and acetylated histone H3 and
H4 to CCL2 promoter are responsible for thrombin induced CCL2 expression in HLF
cells. In addition, p300 inhibition attenuates both thrombin induced-CCL2
expression and histone H3 and H4 acetylation in HLFs, suggesting that p300 is
involved in thrombin-induced CCL2 expression via hyperacetylating histone H3 and
H4. Our data further showed that p300 also regulates CCL2 expression via
interaction with NF-kappaB p65, as depletion of p300 inhibits both NF-kappaB p65
activation and its binding to CCL2 promoter. The findings strongly suggest that
epigenetic dysregulation and the interaction between histone acetyltransferase
and transcription factor may be responsible for thrombin induced-CCL2 expression
in HLFs. Increased understanding of the epigenetic mechanisms of CCL2 regulation
may provide opportunities for identifying novel molecular targets for therapeutic
purposes. J. Cell. Biochem. 118: 4012-4019, 2017. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28407301
TI - Impact of clean intermittent catheterization on quality adjusted life years
(QALYs) in spinal cord injury patients with neurogenic urinary incontinence.
AB - AIMS: The impact of clean intermittent catheterization (CIC) on quality adjusted
life years (QALYs) gained in adults' spinal cord injury population with
neurogenic urinary incontinence (UI). METHODS: Patients were recruited from the
national registry January-June 2014. The inclusion criteria were adults,
neurogenic UI due to spinal cord injury (SCI), use of collection devices and CIC
for more than 6 months. The exclusion criteria were inability to perform CIC,
cancer of the lower urinary tract and fistulas formation. Measurement tools were
the International Consultation on Incontinence Questionnaire-Urinary Incontinence
Short Form (ICIQ-UI SF) and an estimation of life expectancy by the national
registry. The calculation of the weighting factor (WF) was obtained by linear
transformation of the ICIQ-UI SF total score. A score was transformed to the
range from 0 (worst impact) to 1 (no impact). The QALYs was calculated as the
weighting factor * life expectancy in years. RESULTS: A total of 229/365 patients
were involved in this study (63%). Patients before CIC reached an ICIQ mean score
of 14.83, WF of 0.29, and QALYs of 9.02 during life expectancy. After 6 months of
follow-up using CIC, ICIQ reached 9.12, WF 0.57 and QALYs 17.45. The number of
QALYs increased by 93.5% and UI evaluated with the ICIQ-UI SF decreased by 38.5%
(P < 0.01). CONCLUSIONS: The CIC of the urinary bladder statistically
significantly increased the number of QALYs and reduced the degree of UI in SCI
patients.
PMID- 28407302
TI - Posttranscriptional Interaction Between miR-450a-5p and miR-28-5p and STAT1 mRNA
Triggers Osteoblastic Differentiation of Human Mesenchymal Stem Cells.
AB - We demonstrate that the interaction between miR-450a-5p and miR-28-5p and signal
transducer and activator of transcription 1 (STAT1) mRNA correlates with the
osteoblastic differentiation of mesenchymal stem cells from human exfoliated
deciduous teeth (shed cells). STAT1 negatively regulates runx-related
transcription factor 2 (RUNX2), which is an essential transcription factor in
this process. However, the elements that trigger osteoblastic differentiation and
therefore pause the inhibitory effect of STAT1 need investigation. Usually, STAT1
can be posttranscriptionally regulated by miRNAs. To test this, we used an in
vitro model system in which shed cells were chemically induced toward
osteoblastic differentiation and temporally analyzed, comparing undifferentiated
cells with their counterparts in the early (2 days) or late (7 or 21 days)
periods of induction. The definition of the entire functional genome expression
signature demonstrated that the transcriptional activity of a large set of mRNAs
and miRNAs changes during this process. Interestingly, STAT1 and RUNX2 mRNAs
feature contrasting expression levels during the course of differentiation. While
undifferentiated or early differentiating cells express high levels of STAT1
mRNA, which was gradually downregulated, RUNX2 mRNA was upregulated toward
differentiation. The reconstruction of miRNA-mRNA interaction networks allowed
the identification of six miRNAs (miR-17-3p, miR-28-5p, miR-29b, miR-29c-5p, miR
145-3p, and miR-450a-5p), and we predicted their respective targets, from which
we focused on miR-450a-5p and miR-28-5p STAT1 mRNA interactions, whose
intracellular occurrence was validated through the luciferase assay.
Transfections of undifferentiated shed cells with miR-450a-5p or miR-28-5p mimics
or with miR-450a-5p or miR-28-5p antagonists demonstrated that these miRNAs might
play a role as posttranscriptional controllers of STAT1 mRNA during osteoblastic
differentiation. J. Cell. Biochem. 118: 4045-4062, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28407303
TI - Rifampicin reverses nicardipine effect inducing uncontrolled essential
hypertension.
AB - Dihydropyridine calcium-channel blockers are a known substrate for the cytochrome
P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent
inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine
metabolism. We report a case of a 67-year-old hypertensive female treated with a
four-drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg
bid), who was admitted for septic arthritis of the knee requiring antibiotic
treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after
rifampicin initiation, she presented with Posterior Reversible Encephalopathy
Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of
previously controlled hypertension was partially due to nicardipine
ineffectiveness. Plasma nicardipine concentration was assessed through high
performance liquid chromatography 5 hours after coadministration of the two drugs
and proved undetectable.
PMID- 28407305
TI - Female striated urogenital sphincter contraction measured by shear wave
elastography during pelvic floor muscle activation: Proof of concept and
validation.
AB - AIMS: Investigation of the function of the striated urogenital sphincter (SUS) is
challenging because it is difficult to access and requires invasive measures.
Ultrasound shear wave elastography (SWE) is a non-invasive real-time technique
used to estimate tissue stiffness. As muscle stiffness can be used as an estimate
of muscle force, SWE provides an opportunity to study contraction of the peri
urethral musculature. Validation of SWE to study SUS during functional tasks,
such as pelvic floor muscle contractions, is required prior to application in
clinical populations. METHODS: Ten healthy females (34[5] years) participated.
Stiffness in a region expected to contain the SUS was quantified using SWE at
rest and during a pelvic floor muscle contractions performed at 10%, 25%, and 50%
of maximal voluntary contraction (MVC). Two repetitions were performed for 10 s.
RESULTS: During contraction, stiffness increased in the region of the SUS in all
participants and at all contraction intensities. Multiple regions of increased
stiffness were detected, with 95.8% of regions situated ventral to the mid
urethra within the anatomical area of the SUS. The increase in stiffness was
greater for 50% MVC than both 10% and 25% MVC contraction intensities (P < 0.01).
CONCLUSIONS: Stiffness increased within the anatomical region of the SUS during
voluntary pelvic floor muscle contractions with predictable response to changes
in contraction intensity. These observations support the potential for ultrasound
SWE to study SUS function non-invasively.
PMID- 28407304
TI - A Tumor Suppressor Gene Product, Platelet-Derived Growth Factor Receptor-Like
Protein Controls Chondrocyte Proliferation and Differentiation.
AB - The platelet-derived growth factor receptor-like (PDGFRL) gene is regarded as a
tumor suppressor gene. However, nothing is known about the molecular function of
PDGFRL. In this study, we initially clarified its function in chondrocytes. Among
all cell lines examined, the PDGFRL mRNA level was the highest in chondrocytic
HCS-2/8 cells. Interestingly, the proliferation of chondrocytic HCS-2/8 cells was
promoted by PDGFRL overexpression, whereas that of the breast cancer-derived MDA
MB-231 cells was inhibited. Of note, in PDGFRL-overexpressing HCS-2/8 cells, the
expression of chondrocyte differentiation marker genes, SOX9, ACAN, COL2A1,
COL10A1, and ALP, was decreased. Moreover, we confirmed the expression of PDGFRL
mRNA in normal cartilage tissue and chondrocytes. Eventually, the expression of
PDGFRL mRNA in condrocytes except in the case of hypertrophic chondrocytes was
demonstrated in vivo and in vitro. These findings suggest that PDGFRL plays the
different roles, depending upon cell types. Particularly, in chondrocytes, PDGFRL
may play a new and important role which is distinct from the function previously
reported. J. Cell. Biochem. 118: 4033-4044, 2017. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28407306
TI - The influence of the emergence profile on the amount of undetected cement excess
after delivery of cement-retained implant reconstructions.
AB - OBJECTIVE: To test whether or not one of two emergence profile designs (concave
or convex) is superior to the other in terms of remaining cement following
cementation of reconstructions on individualized abutments and careful cement
removal. MATERIALS AND METHODS: A central incisor with a single implant-supported
reconstruction was selected as a model. Six types of abutments (n = 10) with two
different emergence profile designs (concave (CC) and convex (CV)) and three
crown-abutment margin depths (epimucosal, 1.5 mm submucosal, 3 mm submucosal)
were fabricated through a CAD/CAM procedure. Lithium disilicate reinforced
ceramic crowns were cemented with chemically polymerized resin cement. A blinded
investigator attempted to remove all cement excess. Thereafter, the entire
reconstruction was unscrewed and analyzed for the overall amount and the depth of
cement excess. Kruskal-Wallis and Mann-Whitney tests were used to investigate
differences between groups. When more than two groups were compared between each
other, a Bonferroni correction of the P value was performed. RESULTS: Concave
abutments presented significantly more cement remnants than CV abutments when the
entire abutment area of the epimucosal margin groups was evaluated (CC0 mm: mean
2.31 mm2 (SD 0.99) vs. CV0 mm: mean 1.57 mm2 (SD 0.55); P = 0.043). A
statistically significant increase in remnants was detected when the crown
abutment margin was located more submucosally for every abutment studied (0 mm
vs. 1.5 mm: P < 0.000, 0 mm vs 3 mm: P < 0.000, 1.5 mm vs. 3 mm: P < 0.000). The
buccal quadrant demonstrated the least, whereas the oral and interdental
quadrants showed the greatest amount of cement excess. CONCLUSIONS: Concave
emergence profile abutments and deep crown-abutment margin positions increased
the risk of cement excess. Oral and interdental areas are more prone to cement
remnants than other surface areas.
PMID- 28407307
TI - Adenosine A1 receptors measured with 11 C-MPDX PET in early Parkinson's disease.
AB - Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1
Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A
receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in
indirect-pathway neurons. The aim of this study was to investigate the cerebral
density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans
with the radioligand 8-dicyclopropylmethyl-1-11 C-methyl-3-propylxanthine (11 C
MPDX). We studied 10 drug-naive patients with early PD. Each patient was also
examined for dopamine transporters (DATs) and D2 Rs by PET using 11 C-2-beta
carbomethoxy-3-beta-(4-fluorophenyl)-tropane (11 C-CFT) and 11 C-raclopride (11 C
RAC), respectively. Ten elderly, healthy volunteers were recruited as controls
for 11 C-MPDX PET scanning and eight elderly volunteers were recruited as
controls for 11 C-CFT and 11 C-RAC PET scanning. The PET scans revealed a
decrease in the uptake ratio index (URI) of 11 C-CFT and an increase in the URI
of 11 C-RAC in patients. In the temporal lobe, the binding potential for 11 C
MPDX was higher in the patient group than in healthy subjects, but not in the
other regions examined, including the striatum. In patients, we observed motor
symptom asymmetry and a relationship between parkinsonism and the striatal
density of DATs, but not A1 R density. In the putamen of early PD, asymmetrical
down-regulation of A2A Rs is likely a compensatory mechanism in response to a
decrease in dopamine. However, our study suggests that A1 Rs are unaltered in the
putamen of early PD.
PMID- 28407308
TI - Methods of RNA preparation affect mRNA abundance quantification of reference
genes in pig maturing oocytes.
AB - To ensure accurate normalization and quantification of target RNA transcripts
using reverse transcription quantitative polymerase chain reaction (RT-qPCR),
most studies focus on the identification of stably expressed gene(s) as internal
reference. However, RNA preparation methods could also be an important factor,
especially for test samples of limited quantity (e.g. oocytes). In this study, we
aimed to select appropriate reference gene(s), and evaluate the effect of RNA
preparation methods on gene expression quantification in porcine oocytes and
cumulus cells during in vitro maturation. Expression profiles of seven genes
(GAPDH, 18S, YWHAG, BACT, RPL4, HPRT1 and PPIA) were examined, on RNA samples
extracted from cumulus cells (RNeasy Kit) and oocytes (RNeasy Kit and Lysis Kit)
during in vitro maturation, respectively. Interestingly, different RNA
preparation methods were found to potentially affect the quantification of
reference gene expression in pig oocytes cultured in vitro. After geNorm
analyses, the most suitable genes for normalization were identified, GAPDH/18S
for cumulus cells and YWHAG/BACT for oocytes, respectively. Thus, our results
provide useful data and information on the selection of better reference genes
and RNA preparation method for related functional studies.
PMID- 28407309
TI - Cadmium Exposure and Osteoporosis: A Population-Based Study and Benchmark Dose
Estimation in Southern China.
AB - This study aimed to assess the association between osteoporosis and long-term
environmental Cd exposure through diet in southern China. A total of 1116
subjects from a Cd-polluted area and a non-Cd-polluted area were investigated.
All subjects met the criteria of having been living in the investigated area for
more than 15 years and lived on a subsistence diet of rice and vegetables grown
in that area. Besides bone mineral density, the levels of urinary markers of
early renal impairment, such as urinary N-acetyl-beta-D-glucosaminidase (NAG),
alpha1 -microglobulin, beta2 -microglobulin, and urinary albumin, were also
determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to
87.31 ug/g creatinine, with a median of 3.97 ug/g creatinine. Multivariate linear
regression models indicated a significant negative association of urinary Cd
concentrations with bone mineral density. In logistic regression models, both
categorical and continuous urinary Cd concentrations were positively associated
with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary
Cd concentration had greater odds of osteoporosis compared with subjects in the
first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to
5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94,
respectively). Additional adjustment for levels of urinary markers did not
attenuate the associations. No evidence existed of an interaction between urinary
Cd concentration and renal function using levels of urinary markers, and
estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose
and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) ug/g creatinine,
with benchmark response set at 5% and 10%, respectively. The benchmark dose of
urinary Cd was lower in women than in men. This study demonstrated an inverse
association between the body burden of Cd and osteoporosis. The toxic effect of
Cd on bone may occur in parallel to nephrotoxicity. (c) 2017 American Society for
Bone and Mineral Research.
PMID- 28407310
TI - Totally implantable hearing system: Five-year hearing results.
AB - OBJECTIVES/HYPOTHESIS: 1) To provide long-term hearing outcome measures of a
totally implantable hearing system (implant) and compare to the baseline unaided
(BLU) and baseline aided (BLA) conditions, and 2) discuss relevant safety
measures. STUDY DESIGN: Prospective, nonrandomized, multicenter, single-subject
as-own-control design. METHODS: Fifty-one subjects with mild to severe
sensorineural hearing loss were implanted between 2008 and 2009 and enrolled in
this postmarket approval study in the setting of private and hospital-based
practices. Forty-nine of these subjects completed the 5-year study, which
included annual follow-ups. Primary effectiveness endpoints were speech reception
threshold (SRT) and word recognition scores at 50 dB (WRS50s). Secondary
effectiveness endpoints were WRSs and the Abbreviated Profile of Hearing Aid
Benefit (APHAB) scores. Adverse Device Effects (ADEs) and Serious Adverse Device
Effects (SADEs) reported during the study period and a comparison of bone
conduction scores are submitted as safety measures. RESULTS: Compared to the BLA
condition, 1) SRT scores were improved at every annual follow-up; 2) WRS50s were
better in 49%, and the same in 41% at the 5-year follow-up; 3) WRSs were improved
by 17% at the 5-year follow-up; and 4) APHAB scores were improved in most
subscales at every annual follow-up. There were three SADEs in three subjects and
15 ADEs in 11 subjects. Bone conduction scores increased by 3.7 dB at the 5-year
follow-up. Average battery life was 4.9 years. CONCLUSIONS: The implant compared
favorably to the subjects' hearing aid throughout the 5-year period in all of the
areas measured and was found to be safe. LEVEL OF EVIDENCE: 2b. Laryngoscope,
128:210-216, 2018.
PMID- 28407311
TI - Biological Variability in Serum Cortisol Concentration Post-adrenocorticotropic
Hormone Stimulation in Healthy Dogs.
AB - BACKGROUND: The ACTH stimulation has low sensitivity for the diagnosis of
hypercortisolism possibly as a result of biological and analytical variability.
HYPOTHESIS/OBJECTIVES: To report the components of biological and analytical
variability in serum cortisol concentration post-ACTH stimulation ([cortisol]) in
healthy dogs. ANIMALS: Fourteen healthy harrier hound dogs. METHODS: The data
were extracted from a separate, prospective, randomized, double-blinded,
controlled discovery study in which dogs treated with vehicle control and 4
different doses of cortisone acetate (CA) for 7 days had an ACTH stimulation test
performed to confirm the dose-dependent effect of CA. The index of individuality
(IoI), the critical difference between sequential measurements (CD ), and the
number of measurements required to assess the homeostatic set point (HSP) of
[cortisol] with confidence intervals (CI) of 90 and 95% were estimated. RESULTS:
The IoI was equal to 1.1 and the CD was 3.3 MUg/dL (92 nmol/L). The number of
measurements required to assess the HSP of [cortisol] with CI of 90 and 95% were
3 and 15, respectively. Additionally, mean [cortisol] was higher in males than in
females (13.3 +/- 4 MUg/dL [366 +/- 114 nmol/L] vs. 11.5 +/- 2.5 MUg/dL [318 +/-
65 nmol/L], respectively; P = .046). As expected, treatment with CA resulted in a
dose-dependent suppression of [cortisol]. CONCLUSIONS AND CLINICAL IMPORTANCE:
False-negative test results in hypercortisolism could occur when [cortisol] is
outside of the individual's HSP and within the reference interval. The large CD
emphasizes the importance of assessing clinically relevant parameters in the
diagnosis and monitoring of HC.
PMID- 28407312
TI - Nasopharyngeal papillomas treated with CO2 laser and human papillomavirus
vaccination.
AB - This case report describes the use of CO2 laser and quadrivalent human
papillomavirus (HPV) vaccination in two patients with nasopharyngeal HPV11
positive recurrent respiratory papillomas (RRP). These patients initially
underwent CO2 laser excision but developed recurrent lesions and underwent HPV
vaccination as adjunct therapy. The recurrent lesions shrank after vaccination
and were again excised with CO2 laser. Subsequently, these patients had no
recurrence of lesions on long-term follow-up at 33 months or 6 years after
surgery. Thus, in patients with nasopharyngeal RRP, resection with CO2 laser, and
HPV vaccination as adjunct therapy should be considered in HPV11-associated
cases. Laryngoscope, 127:2279-2281, 2017.
PMID- 28407313
TI - Prognosis of primary tracheal tumor: A population-based analysis.
AB - BACKGROUND: To elucidate the survival outcomes of tracheal tumors and to propose
the potential stage of tracheal tumors. METHOD: All cases of primary tracheal
malignant tumors were extracted from the Surveillance, Epidemiology, and End
Results database (SEER) during 1973-2013. The overall survival was calculated
using Kaplan-Meier method. Cox regression was utilized to identify the prognostic
factors. RESULT: A total of 287 cases were finally included. The median age of
the patients was 59 years. Male patients accounted for 56.1%. The median survival
was 57 months. Patients were categorized as Extension1 to 4 (E1-4) and N0-N3. E1
group with size <4 cm had the best prognosis. While E1 >4 cm, E2 and E3 <3 cm
groups had similar outcomes, which were superior to E3 >3 cm group. E4 was the
worst. N0 patients had ideal prognosis, which were better than N1 and N2
patients. The 3-year survival rates of each T category were 74.7%, 57.3%, 28.1%,
and 9.1%, respectively. In multivariate analysis, age, histology, tumor size, and
extension were independent prognostic factors. CONCLUSION: Patients with old age,
large tumor size, advanced extension or no surgery may have worse prognosis. The
proposed T category of tracheal tumor incorporating tumor extension and size
helped to predict survival outcomes.
PMID- 28407314
TI - On the pull: periplasmic trapping of sugars before transport.
AB - Bacteria have evolved many routes for taking up nutrients, demonstrating great
versatility in the types and mechanism of uptake used in different physiological
conditions. The discovery of a single transporter in the bacterium Advenella
mimigardefordensis for the uptake of five different sugars, including L-glucose
and D-xylose, is described in this issue (Meinert et al., ), providing yet
another example of the surprising adaptability of bacterial transport strategies.
The transporter identified is a tripartite ATP-independent (TRAP) transporter,
not previously associated with sugar transport, and in fact does not transport
the sugars directly at all, rather requiring them to be converted in the
periplasm to their respective sugar acid forms before transport through what
appears to be a novel general sugar acid transporter. In this commentary, I
describe how this process is consistent with the known mechanisms of TRAP
transporters and consider how the role of sugar oxidation, or oxidative
fermentation, operates with multiple hexose and pentose sugars. Finally I suggest
that the periplasmic conversion of nutrients acquired across the outer membrane,
before transport across the inner membrane, could have potentially useful
biological functions in Gram negative bacteria.
PMID- 28407315
TI - Drugs with antidepressant properties affect tryptophan metabolites differently in
rodent models with depression-like behavior.
AB - The metabolism of tryptophan through kynurenine and serotonin pathways is linked
to depression. Here, effects of different drugs with antidepressant properties
(vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in
different brain regions and plasma were examined using tandem mass spectrometry
(LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression,
and its controls: Flinders Sensitive Line and Sprague-Dawley rats. Protein levels
of kynurenine pathway enzymes were measured in the brains and livers of these rat
strains. Furthermore, effects of vortioxetine on tryptophan metabolites were
assessed in the cortical regions of lupus mice (MRL/MpJ-FasIpr ), a murine model
of increased depression-like behavior associated with inflammation. Sustained
vortioxetine or fluoxetine (at doses aimed to fully occupy serotonin transporter
via food or drinking water for at least 14 days) reduced levels of the
excitotoxin quinolinic acid (QUIN) in various brain regions in all rats.
Furthermore, chronic vortioxetine reduced levels of QUIN in MRL/MpJ-FasIpr mice.
Acute i.p. administration of fluoxetine (10 mg/kg) or vortioxetine (10 mg/kg) led
to reduced brain 5-hydroxyindoleacetic acid in Sprague-Dawley rats (2, 4, 6, and
8 h) and a similar trend was evident in Flinders Sensitive Line and Flinders
Sensitive Line rats after 4 h. In contrast, single or repeated administration of
ketamine (15 mg/kg i.p.) did not induce significant changes in metabolite levels.
In conclusion, sustained vortioxetine and fluoxetine administration decreased
QUIN independent of species, while ketamine was ineffective. These results
support the hypothesis that modulating tryptophan metabolism may be part of the
mechanism of action for some antidepressants.
PMID- 28407316
TI - Double Asymmetric Hydrogenation of Linear beta,beta-Disubstituted alpha,beta
Unsaturated Ketones into gamma-Substituted Secondary Alcohols using a Dual
Catalytic System.
AB - Double asymmetric hydrogenation of linear beta,beta-disubstituted alpha,beta
unsaturated ketones catalyzed by the DM-SEGPHOS/DMAPEN/RuII complex with t-C4 H9
OK afforded the gamma-substituted secondary alcohols in high diastereo- and
enantioselectivities. Some mechanistic experiments suggested that two different
reactive species, type (I) and (II), were reversibly formed in this catalytic
system: Type (I) with the diamine ligand DMAPEN enantioselectively hydrogenated
the enones into the chiral allylic alcohols, and type (II) without the diamine
ligand diastereoselectively hydrogenated the allylic alcohols into the gamma
substituted secondary alcohols. This dual catalysis protocol was successfully
applied to the reaction of a variety of aliphatic- and aromatic-substituted enone
substrates.
PMID- 28407317
TI - Reconstruction of quadriceps function with composite free tissue transfers
following sarcoma resection.
AB - : BACKGROUND AND OBJECTIVES Wide margin resection of a soft tissue sarcoma (STS)
may require extensive removal of quadriceps muscle with or without the knee
extensor mechanism. The objective of this study is to present present the use of
a combined functional muscle transfer and soft tissue coverage through the use of
chimeric anterolateral thigh flaps. METHODS: Patients were retrospectively
reviewed who underwent deep STS resection of the anterior compartment of the
thigh with functional reconstruction of knee extension using a contralateral free
anterolateral thigh (ALT) flap. RESULTS: Three patients with an average age 53.6
years (range: 33-66) were included. Average follow-up was 82 weeks (76-92
months). Full active extension was regained in 66% of patients with all patients
regaining active extensor capabilities beyond 100 degrees . The mean Knee Society
Score was 83.3 (range; 76-92) and Musculoskeletal Tumor Society Score 21.6
(range; 19-21). Isometric knee extensor strength exceeded 4+/5 in all patients.
CONCLUSION: Following soft tissue sarcoma resections of the lower extremity,
chimeric anterolateral thigh flaps for restoration of knee extension can provide
significant improvements in the potential for ambulation and regaining quadriceps
function.
PMID- 28407318
TI - Comparison of three rapid influenza diagnostic tests with digital readout systems
and one conventional rapid influenza diagnostic test.
AB - BACKGROUND: Rapid influenza diagnostic tests (RIDTs) show variable sensitivities
in clinical settings. We aimed to compare three digital RIDTs and one
conventional RIDT. METHODS: We assessed 218 nasopharyngeal swabs from patients
between neonates and 90 years old in 2016. Three digital RIDTs were BUDDI, Sofia
Influenza A+B Fluorescence Immunoassay, Veritor System Flu A+B assay. One
conventional test was the SD Bioline Influenza Ag A/B/A(H1N1/2009). All test
results were compared with those from the Anyplex Flu A/B Typing Real-time
Detection real-time PCR. The four RIDTs were tested with diluted solutions from
the National Institute for Biological Standards and Control (NIBSC) to compare
lower detection limit. Cross-reactivity of four RIDTs within other respiratory
viruses was identified. RESULTS: For influenza A, BUDDI, Sofia, Veritor, and
Bioline showed 87.7%, 94.5%, 87.7%, and 72.6% sensitivity, and 100%, 97.7%,
96.5%, and 100% specificity. For influenza B, BUDDI, Sofia, Veritor, and Bioline
showed 81.7%, 91.7%, 81.7%, and 78.3% sensitivity, and 100%, 95.3%, 100%, and
100% specificity, respectively. Each RIDT could detect diluted NIBSC solution,
according to the level of dilution and specific influenza subtypes. Cross
reactivity of four RIDTs with other respiratory viruses was not noted.
CONCLUSIONS: Sofia showed the highest sensitivity for influenza A and B
detection. BUDDI and Veritor showed higher detection sensitivity than a
conventional RIDT for influenza A detection, but similar results for influenza B
detection. Further study is needed to compare the test performance of RIDTs
according to specific, prevalent influenza subtypes.
PMID- 28407320
TI - Role of TLR4 and miR-155 in peripheral blood mononuclear cell-mediated
inflammatory reaction in coronary slow flow and coronary arteriosclerosis
patients.
AB - BACKGROUND: To study the role of toll-like receptor 4 (TLR4) and MicroRNA-155
(miR-155) in the peripheral blood mononuclear cell (PBMC)-mediated inflammation
in coronary slow flow (CSF) and coronary arteriosclerosis. METHODS: Patients were
divided into acute coronary syndrome (ACS), stable angina pectoris (SAP), CSF,
and healthy control (HC) groups. The isolated PBMCs were treated with
lipopolysaccharide (LPS)/and antagomiR-155. TLR4, miR-155, and the concentrations
of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1, and IL-10 were
measured. RESULTS: Before LPS intervention, the TLR4, TNF-alpha, IL-1, and IL-6
levels were higher and the level of miR-155, IL-10 was lower in the ACS group
compared with the SAP, CSF, and HC groups. After exposure to LPS, the levels of
TLR4, miR-155, TNF-alpha, IL-1, and IL-6 were increased and the level of IL-10
was decreased in the SAP and CSF groups compared with the HC group. But when over
expressing antagomiR-155 into PBMCs from SAP and CSF groups, the miR-155
expression, and TNF-alpha, IL-6, and IL-1 secretion increase induced by LPS were
restrained. CONCLUSIONS: TLR4, miR-155, and inflammatory cytokines may be closely
related to ACS. LPS can induce TLR4, miR-155 expression and inflammatory response
in SAP and CSF patients. AntagomiR-155 can inhibit this inflammatory response.
PMID- 28407319
TI - Effect of Intravenous or Perivascular Injection of Synthetic Adrenocorticotropic
Hormone on Stimulation Test Results in Dogs.
AB - BACKGROUND: Standard protocols for adrenocorticotropic hormone (ACTH) stimulation
testing (ACTHst) often involve intravenous (IV) injection of corticotropin. ACTH
might be unintentionally injected into the perivascular (PV) space. OBJECTIVE: To
compare stimulation test results after IV and PV injections of ACTH. ANIMALS:
Twenty privately owned dogs were studied: 10 healthy and 10 with trilostane
treated naturally occurring hyperadrenocorticism (HAC). METHODS: Prospective
study. Each of 20 dogs underwent 2 ACTHst not <4 nor more than 14 days apart.
Five healthy and 5 HAC dogs had an IV ACTHst first and PV second; 5 healthy and 5
HAC dogs had a PV ACTHst first and IV second. Blood samples for measurement of
serum cortisol concentration were collected before and 1 hour after ACTH
administration. RESULTS: No significant difference in results was demonstrated
when comparing serum cortisol concentrations after IV and PV ACTH administration
in all 20 dogs (median MUg/dL; interval MUg/dL: 8.2; 1.4-17.4 versus 7.8; 0.9
16.9; P = .23). No significant difference in results was demonstrated when
comparing serum cortisol concentrations after IV and PV ACTH administration in
the 10 healthy dogs (median MUg/dL; interval MUg/dL: 10.9; 7.3-17.4 versus 10.6;
7.1-16.9; P = .54) or in the 10 HAC dogs (median MUg/dL; interval MUg/dL: 6.3;
1.4-8.6 versus 5.2; 0.9-8.7; P = .061). CONCLUSIONS AND CLINICAL IMPORTANCE:
Perivascular administration of ACTH does not significantly alter stimulation test
results in healthy dogs or in dogs with HAC undergoing therapy with trilostane.
PMID- 28407321
TI - Stability and Change in Posttraumatic Distress: A 7-Year Follow-Up Study of
Mothers and Young Children Exposed to Cumulative Trauma.
AB - In situations of cumulative trauma, it is often unclear why some people remain
resilient, whereas others experience distress, and how likely these responses are
to change over time. To investigate the constancy of responses to cumulative
trauma, stability and change in posttraumatic distress and resistance (as defined
by no evidence of clinical symptoms) were assessed twice in 140 Israeli children
and mothers exposed to continual rocket attacks over approximately 7 years, when
the children were 2-4 (Time 1) and 9-11 years of age (Time 2). Measures included
trauma exposure, posttraumatic and depressive symptoms, and child behavioral
problems. We identified 4 longitudinal courses (LCs): resilient (resistance at
Time 1 and Time 2), recovered (clinical distress at Time 1 and resistance at Time
2), developed symptoms (resistance at Time 1 and clinical distress at Time 2),
and chronic distress (clinical distress at Time 1 and Time 2). Results showed
more stability than change in the frequencies of resistance at both times of
measurement. The resilient LC was the most common longitudinal course for both
mothers and children. Multinomial regression models indicated that maternal
posttraumatic symptoms predicted the recovered and chronic distress LCs of the
children.
PMID- 28407322
TI - Effect of Intravenous Small-Volume Hypertonic Sodium Bicarbonate, Sodium
Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in
Hyperkalemic Neonatal Calves with Diarrhea.
AB - BACKGROUND: Hyperkalemia is a frequently observed electrolyte imbalance in
dehydrated neonatal diarrheic calves that can result in skeletal muscle weakness
and life-threatening cardiac conduction abnormalities and arrhythmias.
HYPOTHESIS: Intravenous administration of a small-volume hypertonic NaHCO3
solution is clinically more effective in decreasing the plasma potassium
concentration (cK) in hyperkalemic diarrheic calves than hypertonic NaCl or
glucose solutions. ANIMALS: Twenty-two neonatal diarrheic calves with cK >5.8
mmol/L. METHODS: Prospective randomized clinical trial. Calves randomly received
either 8.4% NaHCO3 (6.4 mL/kg BW; n = 7), 7.5% NaCl (5 mL/kg BW; n = 8), or 46.2%
glucose (5 mL/kg BW; n = 7) IV over 5 minutes and were subsequently allowed to
suckle 2 L of an electrolyte solution. Infusions with NaHCO3 and NaCl provided an
identical sodium load of 6.4 mmol/kg BW. RESULTS: Hypertonic NaHCO3 infusions
produced an immediate and sustained decrease in plasma cK. Hypertonic glucose
infusions resulted in marked hyperglycemia and hyperinsulinemia, but cK remained
unchanged for 20 minutes. Between 30 and 120 minutes after initiation of
treatment, the most marked decrements in cK from baseline occurred in group
NaHCO3 , which were significantly (P < .05) larger during this period of time
than in calves in group NaCl, but not group glucose. After 120 minutes, the mean
decrease in cK from baseline was -26 +/- 10%, -9 +/- 8%, and -22 +/- 6% in groups
NaHCO3 , NaCl, and glucose, respectively. CONCLUSIONS/CLINICAL IMPORTANCE: Small
volume hypertonic NaHCO3 infusions appear to have clinical advantages for the
rapid resuscitation of hyperkalemic diarrheic calves, compared to hypertonic NaCl
or glucose solutions.
PMID- 28407324
TI - Changes in nutrient concentrations of leaves and roots in response to global
change factors.
AB - Global change impacts on biogeochemical cycles have been widely studied, but our
understanding of whether the responses of plant elemental composition to global
change drivers differ between above- and belowground plant organs remains
incomplete. We conducted a meta-analysis of 201 reports including 1,687
observations of studies that have analyzed simultaneously N and P concentrations
changes in leaves and roots in the same plants in response to drought, elevated
[CO2 ], and N and P fertilization around the world, and contrasted the results
within those obtained with a general database (838 reports and 14,772
observations) that analyzed the changes in N and P concentrations in leaves
and/or roots of plants submitted to the commented global change drivers. At
global level, elevated [CO2 ] decreased N concentrations in leaves and roots and
decreased N:P ratio in roots but no in leaves, but was not related to P
concentration changes. However, the response differed among vegetation types. In
temperate forests, elevated [CO2 ] was related with lower N concentrations in
leaves but not in roots, whereas in crops, the contrary patterns were observed.
Elevated [CO2 ] decreased N concentrations in leaves and roots in tundra plants,
whereas not clear relationships were observed in temperate grasslands. However,
when elevated [CO2 ] and N fertilization coincided, leaves had lower N
concentrations, whereas root had higher N concentrations suggesting that more
nutrients will be allocated to roots to improve uptake of the soil resources not
directly provided by the global change drivers. N fertilization and drought
increased foliar and root N concentrations while the effects on P concentrations
were less clear. The changes in N and P allocation to leaves and root, especially
those occurring in opposite direction between them have the capacity to
differentially affect above- and belowground ecosystem functions, such as litter
mineralization and above- and belowground food webs.
PMID- 28407325
TI - Thomas E. Starzl, M.D., Ph.D. (1926-2017).
PMID- 28407323
TI - Proteogenomic analysis reveals alternative splicing and translation as part of
the abscisic acid response in Arabidopsis seedlings.
AB - In eukaryotes, mechanisms such as alternative splicing (AS) and alternative
translation initiation (ATI) contribute to organismal protein diversity.
Specifically, splicing factors play crucial roles in responses to environment and
development cues; however, the underlying mechanisms are not well investigated in
plants. Here, we report the parallel employment of short-read RNA sequencing,
single molecule long-read sequencing and proteomic identification to unravel AS
isoforms and previously unannotated proteins in response to abscisic acid (ABA)
treatment. Combining the data from the two sequencing methods, approximately
83.4% of intron-containing genes were alternatively spliced. Two AS types, which
are referred to as alternative first exon (AFE) and alternative last exon (ALE),
were more abundant than intron retention (IR); however, by contrast to AS events
detected under normal conditions, differentially expressed AS isoforms were more
likely to be translated. ABA extensively affects the AS pattern, indicated by the
increasing number of non-conventional splicing sites. This work also identified
thousands of unannotated peptides and proteins by ATI based on mass spectrometry
and a virtual peptide library deduced from both strands of coding regions within
the Arabidopsis genome. The results enhance our understanding of AS and
alternative translation mechanisms under normal conditions, and in response to
ABA treatment.
PMID- 28407326
TI - Maternal lactocrine programming of porcine reproductive tract development.
AB - The lactocrine hypothesis for maternal programming of female reproductive tract
development is based on the idea that non-nutritive, milk-borne bioactive factors
(MbFs), delivered from mother to offspring during nursing, play a role in
determining the trajectory of development with long-term consequences in the
adult. Porcine female reproductive tract development is completed postnatally,
and the period during which maternal support of neonatal growth derives
exclusively from colostrum/milk defines a window of opportunity for lactocrine
programming of reproductive tissues. Beyond nutrition, milk serves as a delivery
system for a variety of bioactive factors. Porcine relaxin is a prototypical MbF.
Present in colostrum at highest concentrations at birth, relaxin is transmitted
into the circulation of nursing piglets where it can act on Relaxin receptors
found in neonatal female reproductive tract tissues. This process is facilitated
by the physiology of the maternal-neonatal dyad and the fact that the neonatal
gastrointestinal tract is open to absorb macromolecules for a period of time
postnatally. Age at first nursing and duration of nursing from birth are also
important for porcine female reproductive tract development. These parameters
affect both the quality and quantity of colostrum consumed. Disruption of
lactocrine signaling by feeding milk replacer from birth altered porcine uterine,
cervical, and testicular development by postnatal Day 2. Moreover, insufficient
colostrum consumption in nursing piglets can impair uterine capacity to support
viable litters of optimal size in adulthood. In the pig, lactocrine signaling
supports neonatal organizational events associated with normal reproductive
development and may program adult uterine capacity.
PMID- 28407327
TI - Oncolytic viral therapy for pancreatic cancer.
AB - Outcomes of pancreatic adenocarcinoma (PDA) remain dismal despite extensive
clinical investigation. Combination chemotherapy provides modest improvements in
survival above best supportive care, and immunotherapy has thus far not proven
effective. Nevertheless, growing insight into antitumor immunity and the tumor
microenvironment has inspired the discovery of novel agents targeting PDA.
Oncolytic viruses represent an emerging class of immunotherapeutic agents that
have undergone extensive preclinical investigation and warrant further
investigation in well-designed clinical trials.
PMID- 28407328
TI - Distinctiveness enhances long-term event memory in non-human primates,
irrespective of reinforcement.
AB - Non-human primates are capable of recalling events that occurred as long as 3
years ago, and are able to distinguish between similar events; akin to human
memory. In humans, distinctiveness enhances memory for events, however, it is
unknown whether the same occurs in non-human primates. As such, we tested three
great ape species on their ability to remember an event that varied in
distinctiveness. Across three experiments, apes witnessed a baiting event in
which one of three identical containers was baited with food. After a delay of 2
weeks, we tested their memory for the location of the baited container. Apes
failed to recall the baited container when the event was undistinctive
(Experiment 1), but were successful when it was distinctive (Experiment 2),
although performance was equally good in a less-distinctive condition. A third
experiment (Experiment 3) confirmed that distinctiveness, independent of
reinforcement, was a consistent predictor of performance. These findings suggest
that distinctiveness may enhance memory for events in non-human primates in the
same way as in humans, and provides further evidence of basic similarities
between the ways apes and humans remember past events.
PMID- 28407329
TI - The six-spot-step test - a new method for monitoring walking ability in patients
with chronic inflammatory polyneuropathy.
AB - The aim of this study was to evaluate whether the six-spot-step test (SSST) is
more suitable for monitoring walking ability in patients with chronic
inflammatory polyneuropathy than the timed 25-foot-walking test (T25FW). In the
SSST, participants have to walk as quickly as possible across a field measuring 1
* 5 m, while kicking blocks out of five circles on the floor. Sixty-two patients
and 61 controls performed the SSST and T25FW. Patients also performed the overall
disability sumscore, INCAT sensory sumscore, Medical Research Council sumscore,
and 9-hole-peg-test. Twenty-one patients treated with intravenous immunoglobulin
(IVIG) every 4-6 weeks were tested prior to and 2-3 weeks after treatment and
judged change in their own clinical condition using the patient global impression
of change (PGIC) scale. In patients, SSST ranged from 5.7 to 26.8 s and T25FW
ranged from 3.6 to 12.9 s. Intra-class correlation between repeated tests was
0.97 for SSST and 0.95 for T25FW. Correlation with the additional tests was
stronger for SSST than T25FW. In IVIG-treated patients, the mean change in
walking time was -2.3 s for SSST and -0.6 s for T25FW. The SSST showed larger
responsiveness in terms of effect size, standardized response means, and relative
efficiency. Both ambulation tests correlated moderately to PGIC. The SSST may be
superior to the T25FW in terms of dynamic range, floor effect, and responsiveness
which makes the SSST a possible alternative for monitoring walking ability in
patients with chronic inflammatory polyneuropathy.
PMID- 28407330
TI - Diffusion-Weighted and Magnetization Transfer Imaging in Testicular Spermatogenic
Function Evaluation: Preliminary Results.
AB - PURPOSE: To assess the use of functional magnetic resonance imaging (MRI),
including diffusion-weighted MRI (DWI) and magnetization transfer MRI (MTI) in
evaluating male infertility. MATERIALS AND METHODS: Sixteen men with testicular
spermatogenesis hypofunction confirmed by percutaneous testis biopsy and 31
volunteers (control group B, age range: 20-40 years) with normal semen analysis
including younger (By, n = 15, age range: 20-30 years) and older (Bo, n = 16, age
range: 31-40 years) men underwent pelvic 3T MRI, including DWI and MTI. Apparent
diffusion coefficient (ADC) and magnetization transfer ratio (MTR) were compared.
RESULTS: The ADCs in 32 testes of 16 patients (0.497 +/- 0.037 * 10-3 mm2 /s)
were significantly (P < 0.001) higher than that of control group B (0.460 +/-
0.031 * 10-3 mm2 /s), group By (0.453 +/- 0.018 * 10-3 mm2 /s), and group Bo
(0.461 +/- 0.034 * 10-3 mm2 /s), whereas the MTRs were significantly lower than
that of group B (16.14 +/- 4.20), group By (17.88 +/- 2.00), and group Bo (15.09
+/- 4.28) (P < 0.001). CONCLUSION: Functional MRI, including DWI and MTI, appears
promising for evaluating male infertility with higher ADC and lower MTR in
testicular spermatogenesis hypofunction. LEVEL OF EVIDENCE: 2 Technical Efficacy:
Stage 2 J. Magn. Reson. Imaging 2018;47:186-190.
PMID- 28407331
TI - Room Temperature Sensing Achieved by GaAs Nanowires and oCVD Polymer Coating.
AB - Novel structures comprised of GaAs nanowire arrays conformally coated with
conducting polymers (poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3,4
ethylenedioxythiophene-co-3-thiophene acetic acid) display both sensitivity and
selectivity to a variety of volatile organic chemicals. A key feature is room
temperature operation, so that neither a heater nor the power it would consume,
is required. It is a distinct difference from traditional metal oxide sensors,
which typically require elevated operational temperature. The GaAs nanowires are
prepared directly via self-seeded metal-organic chemical deposition, and
conducting polymers are deposited on GaAs nanowires using oxidative chemical
vapor deposition (oCVD). The range of thickness for the oCVD layer is between 100
and 200 nm, which is controlled by changing the deposition time. X-ray
diffraction analysis indicates an edge-on alignment of the crystalline structure
of the PEDOT coating layer on GaAs nanowires. In addition, the positive
correlation between the improvement of sensitivity and the increasing nanowire
density is demonstrated. Furthermore, the effect of different oCVD coating
materials is studied. The sensing mechanism is also discussed with studies
considering both nanowire density and polymer types. Overall, the novel structure
exhibits good sensitivity and selectivity in gas sensing, and provides a
promising platform for future sensor design.
PMID- 28407332
TI - Transcriptome analysis of severely active chronic spontaneous urticaria shows an
overall immunological skin involvement.
AB - BACKGROUND: The knowledge about chronic spontaneous urticaria (CSU) phenotypes is
based on its clinical characteristics, associated comorbidities, course of the
disease, and its response to the available effective drugs. Genotype expression
and its further correlation with CSU phenotypes are still unknown. We describe
the cutaneous transcriptome of patients suffering a severely active CSU
refractory to antihistamine treatment. METHODS: Through the bioinformatic
analysis of the whole Human Genome with Oligo Microarrays and quantitative real
time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional
(NLS-CSU) and lesional skin (LS-CSU) and peripheral blood were identified in 20
patients suffering from severely active CSU and 10 healthy controls (HCs).
RESULTS: From 39 genes differentially expressed in NLS-CSU when compared with
HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in
epidermal homeostasis and dermal repair. From the analysis comparing LS-CSU with
NLS-CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were
confirmed. Differentially expressed genes in the phenomenon of wheal development
are involved in a variety of biological functions as, epidermal differentiation,
intracellular signal function, transcriptional factors cell cycle
differentiation, inflammation, or coagulation. Differentially expressed genes
that uniformly increase or decrease along the skin worsening until the wheal
appearance is shown. CONCLUSION: The skin of CSU patients with a severely active
disease shows an overall immunological skin involvement showing a peculiar gene
profile.
PMID- 28407333
TI - Bioarchaeological profile of stress and dental disease among ancient high
altitude Himalayan communities of Nepal.
AB - OBJECTIVES: This study examines biological indicators of dental disease and
nonspecific stress in human remains of three high altitude Himalayan
archaeological sites to test whether shared ecological constraints led to similar
bioarchaeological profiles in these markers. METHODS: Samples (n = 170) derive
from three sites in Nepal dating to two periods (400-50 BCE and c. 400-650 CE).
Dental diseases (caries, antemortem tooth loss, and abscesses) were assessed by
both the number of individuals and the number of elements observed, while
childhood stress markers included observation of growth disruptions (enamel
hypoplasia and adult femur length/stature) and cranial porosities. Statistical
analysis included chi-square and Fisher's exact tests for categorical data and
ANOVA and t-tests for metric data. RESULTS: There are significant differences
between the sites and sexes in frequencies of dental diseases in the adult
samples. There are low frequencies of childhood stress markers overall and the
femur length data show no significant differences across sites, but significant
sexual dimorphism within each site. Females have reduced stature compared to
contemporary Tibetan samples residing at a similar elevation. CONCLUSIONS:
Variations in dental disease frequencies between the sites may be due to local
variations in microenvironment, cultural, and/or temporal differences in resource
availability, food consumption and preparation, as well as the age structure of
the samples. The low frequencies of markers for nonspecific stress may be
indicative of the ability of these ancient Himalayan groups to successfully meet
the challenges posed by the extreme conditions of high altitude living through
biocultural adaptations.
PMID- 28407334
TI - Time to cranial computerised tomography for acute traumatic brain injury in
paediatric patients: Effect of the shorter stays in emergency departments target
in New Zealand.
AB - AIM: Timely access to computerised tomography (CT) for acute traumatic brain
injuries (TBIs) facilitates rapid diagnosis and surgical intervention. In 2009,
New Zealand introduced a mandatory target for emergency department (ED) stay such
that 95% of patients should leave ED within 6 h of arrival. This study
investigated whether this target influenced the timeliness of cranial CT scanning
in children who presented to ED with acute TBI. METHODS: We retrospectively
reviewed a random sample of charts of children <15 years with acute TBI from 2006
to 2012. Cases were identified using International Classification of Disease 10
codes consistent with TBI. General linear models investigated changes in time to
CT and other indicators before and after the shorter stays in ED target was
introduced in 2009. RESULTS: Among the 190 cases eligible for study (n = 91 pre
target and n = 99 post-target), no significant difference was found in time to CT
scan pre- and post-target: least squares mean (LSM) with 95% confidence interval
= 68 (56-81) versus 65 (53-78) min, respectively, P = 0.66. Time to neurosurgery
(LSM 8.7 (5-15) vs. 5.1 (2.6-9.9) h, P = 0.19, or hospital length of stay (LSM:
4.9 (3.9-6.3) vs. 5.2 (4.1-6.7) days, P = 0.69) did not change significantly.
However, ED length of stay decreased by 45 min in the post-target period (LSM =
211 (187-238) vs. 166 (98-160) min, P = 0.006). CONCLUSION: Implementation of the
shorter stays in ED target was not associated with a change in the time to CT for
children presenting with acute TBI, but an overall reduction in the time spent in
ED was apparent.
PMID- 28407335
TI - In vitro porcine blastocyst development in three-dimensional alginate hydrogels.
AB - Appropriate embryonic and fetal development significantly impact pregnancy
success and, therefore, the efficiency of swine production. The pre-implantation
period of porcine pregnancy is characterized by several developmental hallmarks,
which are initiated by the dramatic morphological change that occurs as pig
blastocysts elongate from spherical to filamentous blastocysts. Deficiencies in
blastocyst elongation contribute to approximately 20% of embryonic loss, and have
a direct influence on within-litter birth weight variation. Although factors
identified within the uterine environment may play a role in blastocyst
elongation, little is known about the exact mechanisms by which porcine (or other
species') blastocysts initiate and progress through the elongation process. This
is partly due to the difficulty of replicating elongation in vitro, which would
allow for its study in a controlled environment and in real-time. We developed a
three dimensional (3-D) culture system using alginate hydrogel matrices that can
encapsulate pig blastocysts, maintain viability and blastocyst architecture, and
facilitate reproducible morphological changes with corresponding expression of
steroidogenic enzyme transcripts and estrogen production, consistent with the
initiation of elongation in vivo. This review highlights key aspects of the pre
implantation period of porcine pregnancy and the difficulty of studying
blastocyst elongation in vivo or by using in vitro systems. This review also
provides insights on the utility of 3-D hydrogels to study blastocyst elongation
continuously and in real-time as a complementary and confirmatory approach to in
vivo analysis.
PMID- 28407336
TI - Stabilization of Telomeric I-Motif Structures by (2'S)-2'-Deoxy-2'-C
Methylcytidine Residues.
AB - G-quadruplexes and i-motifs are tetraplex structures present in telomeres and the
promoter regions of oncogenes. The possibility of producing nanodevices with pH
sensitive functions has triggered interest in modified oligonucleotides with
improved structural properties. We synthesized C-rich oligonucleotides carrying
conformationally restricted (2'S)-2'-deoxy-2'-C-methyl-cytidine units. The effect
of this modified nucleoside on the stability of intramolecular i-motifs from the
vertebrate telomere was investigated by UV, CD, and NMR spectroscopy. The
replacement of selected positions of the C-core with C-modified residues induced
the formation of stable intercalated tetraplexes at near-neutral pH. This study
demonstrates the possibility of enhancing the stability of the i-motif by
chemical modification.
PMID- 28407337
TI - Protein Dimerization on a Phosphonated Calix[6]arene Disc.
AB - Complex formation between cationic cytochrome c and the water-soluble, poly
anionic p-phosphonatocalix[6]arene (pclx6 ) was investigated. A crystal structure
(at 1.8 A resolution) revealed a remarkable dimeric disc of pclx6 that acts like
glue to mediate a symmetric (C2 ) protein dimer. The calixarene disc has a
diameter of about 1.5 nm and masks about 360 A2 of protein surface. The key
protein-calixarene contacts occur via two linchpin lysines, with additional
contacts provided by a small hydrophobic patch. The protein-calixarene
supramolecular assemblies were observed in solution by size-exclusion
chromatography with multi-angle light scattering and NMR spectroscopy. Using
isothermal titration calorimetry and NMR data, an apparent Kd in the low
micromolar range was determined for the charge-rich protein-calixarene complex.
In contrast to p-sulfonatocalix[4]arene, the larger pclx6 has a single, well
defined binding site that mediates the assembly of cytochrome c in solution.
PMID- 28407338
TI - Tolterodine ER reduced increased bladder wall thickness in women with overactive
bladder. A randomized, placebo-controlled, double-blind, parallel group study.
AB - AIMS: We evaluated the effect of Tolterodine extended release (TER) versus
placebo on bladder wall thickness (BWT) using transvaginal ultrasound in women
with overactive bladder (OAB). MATERIALS AND METHODS: We recruited 79 women with
symptoms of OAB with a mean age of 47 years who had a BWT of at least 5 mm and a
post-micturition volume of less than 50 mL at screening. Subjects received TER 4
mg or placebo once daily for the first 12 weeks of the study. For the subsequent
12 weeks, all subjects received TER 4 mg once daily. BWT was measured at
screening, weeks 12 and 24. Subjects recorded number of micturitions,
incontinence episodes and urgency episodes, and volume voided per micturition at
regular intervals during the study. RESULTS: Treatment with TER for 12 weeks
produced a statistically significant decrease from baseline in BWT (mean [SD] =
0.9 [1.4] mm; P < 0.05) that was not evident following treatment with placebo
(0.2 [1.6] mm; P = 0.54). However, the treatment difference did not reach
statistical significance (LS Mean = -0.4; 95%CI: -1.2, 0.3; P = 0.25). After 12
weeks of treatment, subjects who had taken TER showed an improvement in each
bladder diary variable compared to placebo-treated subjects. CONCLUSIONS: TER may
have a direct effect on BWT in women with OAB. Larger studies are warranted to
further investigate the effect of behavioral interventions and antimuscarinics,
such as TER, on BWT in women with OAB and increased BWT.
PMID- 28407339
TI - An Oxygen-Insensitive Hydrogen Evolution Catalyst Coated by a Molybdenum-Based
Layer for Overall Water Splitting.
AB - For overall water-splitting systems, it is essential to establish O2 -insensitive
cathodes that allow cogeneration of H2 and O2 . An acid-tolerant electrocatalyst
is described, which employs a Mo-coating on a metal surface to achieve selective
H2 evolution in the presence of O2 . In operando X-ray absorption spectroscopy
identified reduced Pt covered with an amorphous molybdenum oxyhydroxide hydrate
with a local structural order composed of polyanionic trimeric units of
molybdenum(IV). The Mo layer likely hinders O2 gas permeation, impeding contact
with active Pt. Photocatalytic overall water splitting proceeded using MoOx
/Pt/SrTiO3 with inhibited water formation from H2 and O2 , which is the
prevailing back reaction on the bare Pt/SrTiO3 photocatalyst. The Mo coating was
stable in acidic media for multiple hours of overall water splitting by
membraneless electrolysis and photocatalysis.
PMID- 28407340
TI - Prescribing cross-education of strength: Is it time?
PMID- 28407341
TI - Response to: postoperative ileus, a diagnosis by exclusion?
PMID- 28407342
TI - Cardiovascular safety of insulin: Between real-world data and reality.
PMID- 28407343
TI - Fluorophores for Excited-State Intramolecular Proton Transfer by an Yttrium
Triflate Catalyzed Reaction of Isocyanides with Thiocarboxylic Acids.
AB - Discovery of new chemical reactivity of a given functional group can often result
in innovative synthesis of important chemical entities that possess unprecedented
properties. We designed and developed a one-step synthesis of 5-amino-4
carboxamidothiazoles 1 by an yttrium-triflate-catalyzed reaction of
thiocarboxylic acids 2 with isocyanides 3. In this reaction, both reactants 2 and
3 deviated from their normal reactivities because of metal coordination. The
resulting heterocycles are novel prototypical structures for the double ESIPT
process. Some of them were excited by visible light irradiation and emitted
fluorescence at the NIR region with large Stokes shift, high quantum yield, and
strong solvatochromism.
PMID- 28407344
TI - Oxidation-Initiated Cyclizations of Pentadienyl Ethers: An Alternative Entry to
the Nazarov Reaction.
AB - Oxidation-initiated Nazarov reactions of 1,4-pentadien-3-yl ethers take place in
the presence of DDQ. Termination by regioselective elimination preserves both
stereocenters created during electrocyclization, providing cyclopentanone
products bearing an exocyclic methylene unit. Use of catalytic DDQ with MnO2 as
terminal oxidant is also described.
PMID- 28407345
TI - Dosimetric impacts of endorectal balloon in CyberKnife stereotactic body
radiation therapy (SBRT) for early-stage prostate cancer.
AB - PURPOSE: In SBRT for prostate cancer, higher fractional dose to the rectum is a
major toxicity concern due to using smaller PTV margin and hypofractionation. We
investigate the dosimetric impact on rectum using endorectal balloon (ERB) in
prostate SBRT. MATERIALS AND METHODS: Twenty prostate cancer patients were
included in a retrospective study, ten with ERB and 10 without ERB. Optimized
SBRT plans were generated on CyberKnife MultiPlan for 5 * 7.25 Gy to PTV under
RTOG-0938 protocol for early-stage prostate cancer. For the rectum and the
anterior half rectum, mean dose and percentage of volumes receiving 50%, 80%,
90%, and 100% prescription dose were compared. RESULTS: Using ERB, mean dose to
the rectum was 62 cGy (P = 0.001) lower per fraction, and 50 cGy (P = 0.024)
lower per fraction for the anterior half rectum. The average V50% , V80% , V90% ,
and V100% were lower by 9.9% (P = 0.001), 5.3% (P = 0.0002), 3.4% (P = 0.0002),
and 1.2% (P = 0.005) for the rectum, and lower by 10.4% (P = 0.009), 8.3% (P =
0.0004), 5.4% (P = 0.0003), and 2.1% (P = 0.003) for the anterior half rectum.
CONCLUSIONS: Significant reductions of dose to the rectum using ERB were
observed. This may lead to improvement of the rectal toxicity profiles in
prostate SBRT.
PMID- 28407346
TI - Vitamin D Receptor Gene Polymorphisms in Serbian Patients With Bronchial Asthma:
A Case-Control Study.
AB - Vitamin D and single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR)
gene are potentially involved in the pathogenesis of bronchial asthma (BA);
however, precise mechanisms by which vitamin D reduces the inflammation and the
role of VDR SNPs in BA are not completely understood. The aim of this study was
to examine the possible associations of FokI, BsmI, ApaI, and TaqI SNPs with BA.
A total of 168 subjects were screened for VDR SNPs using polymerase chain
reaction restriction fragment length polymorphism (PCR-RFLP) method. The obtained
results showed statistically significant differences in the distribution of FokI
genotypes (df = 2; P = 0.008) and alleles (P = 0.002; OR = 0.446; 95%CI = 0.264
0.752) between patients and controls. Distributions of BsmI, ApaI, and TaqI
genotypes and alleles did not show statistical differences. BsmI, ApaI, and TaqI
SNPs are in linkage disequilibrium (LD) in the whole studied group, as well as in
BA patients and controls. The strongest LD was observed between BsmI and TaqI (r2
= 0.69 for all subjects in the study; r2 = 0.75 in BA; r2 = 0.64 in controls),
while lower values of LD were observed for BsmI and ApaI, and ApaI and TaqI SNPs.
This is the first study that examined the association of VDR SNPs (FokI, BsmI,
ApaI, and TaqI) in Serbian patients with BA indicating protective effect of FF
genotype and F allele of FokI SNP on BA development. J. Cell. Biochem. 118: 3986
3992, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407347
TI - Severe depression and anxiety in women with overactive bladder.
AB - AIM: Depression and anxiety are prevalent psychiatric conditions and are
associated with overactive bladder. The objective of this study was to determine
prevalence and severity of anxiety and depression associated with overactive
bladder (OAB) in women. METHODS: 274 women with clinical diagnosis of OAB were
recruited from 2012 to 2015. They were submitted to the International
Consultation on Incontinence Questionnaire-Overactive Bladder (ICIQ-OAB), the
Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). RESULTS:
Severe or moderate depression was present in 59.8% of women and severe or
moderate anxiety was identified in 62.4%. Higher scores of depression and anxiety
were associated with higher scores of ICIQ-OAB (P = 0.0031 and 0.0049). Women
with severe depression had higher nocturia score than those with mild depression
(P = 0.0046). Also, women with severe depression had higher urgency incontinence
score than those with minimal depression (P = 0.0261). Patients with severe
anxiety had higher nocturia score than those with minimal anxiety (P = 0.0118)
and women with moderate anxiety had higher urgency incontinence score than with
minimal anxiety (P = 0.0300). CONCLUSIONS: Moderate or severe depression and
anxiety are prevalent in women with OAB. There is a correlation between intensity
of OAB symptoms with depression and anxiety. Anxiety and depression levels are
mainly related with urgency incontinence and nocturia.
PMID- 28407348
TI - Retrospective evaluation of factors influencing successful skin grafting for
patients with skin cancer of the foot.
AB - Skin grafting is a simple method for reconstruction of a large defect on the
foot. Although skin grafting on the foot sometimes fails, it is not clear what
factors influence the success rate of skin grafting. We analyzed data for 71
patients with skin cancer of the foot who underwent reconstruction of defects
with skin grafting. The factors we evaluated were success rate of skin grafting,
weight-bearing or non-weight-bearing area, immediate or delayed reconstruction,
and whether a tie-over bolster was used or not. The success rates were higher in
patients with lesions in non-weight-bearing areas than in patients with lesions
in weight-bearing areas and in patients who underwent delayed reconstruction than
in patients who received immediate reconstruction. On the other hand, the use of
a tie-over bolster did not improve the success rate. In conclusion, delayed
reconstruction is desirable if the lesion is located in a weight-bearing area.
PMID- 28407349
TI - Low L-Ficolin associated with disease severity during sepsis in adult ICU
patients.
PMID- 28407350
TI - Toroid Formation through a Supramolecular "Cyclization Reaction" of Rodlike
Micelles.
AB - Constructing polymeric toroids with a uniform, tunable size is challenging.
Reported herein is the formation of uniform toroids from poly(gamma-benzyl-l
glutamate)-graft-poly(ethylene glycol) (PBLG-g-PEG) graft copolymers by a two
step self-assembly process. In the first step, uniform rodlike micelles are
prepared by dialyzing the polymer dissolved in tetrahydrofuran (THF)/N,N'
dimethylformamide (DMF) against water. With the addition of THF in the second
step, the rodlike micelles curve and then close end-to-end to form uniform
toroids, which resemble a cyclization reaction.
PMID- 28407351
TI - Grain-Boundary-Free Super-Proton Conduction of a Solution-Processed Prussian-Blue
Nanoparticle Film.
AB - A porous crystal family has been explored as alternatives of Nafion films
exhibiting super-proton conductivities of >=10-2 S cm-1 . Here, the proton
conduction natures of a solution-processed film of nanoparticles (NPs) have been
studied and compared to those of a Nafion film. A mono-particle film of Prussian
blue NPs is spontaneously formed on a self-assembled monolayer substrate by a one
step solution process. A low-temperature heating process of the densely packed,
pinhole-free mono-particle NP film enables a maximum 105 -fold enhancement of
proton conductivity, reaching ca. 10-1 S cm-1 . The apparent highest
conductivity, compared to previously reported data of the porous crystal family,
remains constant against humidity changes by an improved water-retention ability
of the film. In our proposed mechanism, the high-performing solution-processed NP
film suggests that heating leads to the self-restoration of hydrogen-bonding
networks throughout their innumerable grain boundaries.
PMID- 28407352
TI - Copper-Catalyzed Aminothiolation of 1,3-Dienes via a Dihydrothiazine
Intermediate.
AB - Heteroatom-containing organic molecules are of particular interest to medicinal
chemists and materials scientists. A strategy to reach these architectures via
direct difunctionalization of abundant 1,3-dienes is especially attractive.
Herein, we describe the development of a regio- and diastereoselective 1,4
aminothiolation of 1,3-dienes with a sulfur diimide reagent, a copper catalyst,
and alkyl Grignard reagents. This unique protocol provides remote nitrogen and
sulfur functionalities with high levels of stereocontrol. The reaction proceeds
via a tandem hetero-Diels-Alder cycloaddition of N,N'-bis(benzenesulfonyl)sulfur
diimide with 1,3-diene followed by copper-catalyzed Grignard substitution.
Mechanistic studies support a copper catalyzed formation of an unprecedented [10
S-4] sulfurane that reductively eliminates to afford a 3,6-dihydrothiazine, which
is selectively converted to 1,4-aminothiols.
PMID- 28407353
TI - Binding CO2 by a Cr8 Metallacrown.
AB - The {Cr8 } metallacrown [CrF(O2 Ct Bu)2 ]8 , containing a F-lined internal
cavity, shows high selectivity for CO2 over N2 . DFT calculations and absorption
studies support the multiple binding of F-groups to the C-center of CO2 (C???F
3.190(9)-3.389(9) A), as confirmed by single-crystal X-ray diffraction.
PMID- 28407354
TI - Defining mandibular morphology in Robin sequence: A matched case-control study.
AB - Robin Sequence (RS) is classically defined as the triad of micrognathia,
glossoptosis, and airway obstruction. While there remains significant debate over
diagnostic criteria for severity, there is consensus regarding micrognathia as a
defining feature of the condition. The purpose of this study was to compare
mandibular morphology among infants and children with RS to infants and children
without RS using maxillofacial computed tomography. Our hypothesis was that there
are discrete morphologic differences between RS and non-RS mandibles. Our goal
was to determine if there are defined and measureable differences in RS mandible
shape that can be used in defining the sequence. We identified 20 cases with RS
and 20 age- and sex-matched controls without RS. Linear, angular, and composite
measurements were obtained for each patient. Cases had shorter mandibular
sagittal lengths (-27%, p = 0.001), shorter inferior border arc lengths (-11.5%,
p = 0.002), steeper gonial angles (+10.5%, p < 0.001), and narrower symphyseal
angles (-11.5%, p < 0.001). Mandibular shape in RS was more rounded/elliptical (p
< 0.001) and infants with RS had a significantly smaller submental cross
sectional area (-29.4%, p < 0.001). These shape differences anterior to the
gonial angle of the mandible appear to be a defining morphologic feature in RS.
PMID- 28407356
TI - Risk of cancer after anticoagulation in patients with unprovoked venous
thromboembolism: an observational cohort study.
AB - : Essentials Data on long-term cancer risk are controversial in patients with
venous thromboembolism (VTE). We assessed long-term rates and risk factors of
cancer in patients with VTE. Cancer risk after anticoagulation is not higher in
VTE patients than in the general population. VTE recurrence is not predictive of
a future cancer diagnosis. SUMMARY: Background Patients with venous
thromboembolism (VTE) are at risk of having a subsequent cancer diagnosis. The
risk is highest during the first 6 months. Reports on cancer rates thereafter are
controversial. We aimed to assess long-term rates and risk factors of cancer in
patients with VTE. Methods and Results We followed patients with a first
unprovoked VTE after discontinuation of anticoagulation, and excluded those
receiving long-term antithrombotic therapy or with major thrombophilia. The study
endpoint was the occurrence of cancer. Sixty-two (5.2%) of 1188 patients
developed cancer during a median follow-up of 98 months. The cumulative incidence
rates of cancer were 0.7% (95% confidence interval [CI] 0.2-1.2%), 3.1% (95% CI
2.0-4.1%) and 9% (95% CI 6.5-11.5) after 1, 5 and 15 years; these were not
significantly different from those in the matched general population (0.6%, 3.4%,
and 12.2%, respectively). The corresponding standardized incidence ratios (ratio
of the observed cancer cases and the number of cases based on national cancer
incidence rates) of 1.1 (95% CI 0.5-2.5), 1.0 (95% CI 0.6-1.4) and 0.9 (95% CI
0.7-1.2) did not indicate a difference in cancer incidence between our cohort and
the general population. Advancing age (hazard ratio [HR] per decade 1.5, 95% CI
1.2-2.0) and shorter duration of anticoagulation (HR per 1-month decrease 1.3,
95% CI 1.1-1.6) were associated with an increased cancer risk, whereas VTE
recurrence was not (HR 1.17, 95% CI 0.66-2.07). Conclusions Asymptomatic patients
with unprovoked VTE who have completed anticoagulation therapy do not have a
higher cancer risk. The inverse association between the duration of
anticoagulation and the incidence of cancer warrants further investigation.
PMID- 28407355
TI - Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect
against murine hepatic ischemia/reperfusion injury.
AB - Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes
to liver dysfunction and complications after liver surgery and transplantation.
Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of
their reparative immunomodulatory effects in injured tissues. Recent studies have
highlighted beneficial effects of extracellular vesicles from mesenchymal stem
cells (MSC-EV) on tissue injury. The effects of systemically administered mouse
bone marrow-derived MSC-EV were evaluated in an experimental murine model of
hepatic IRI induced by cross-clamping the hepatic artery and portal vein for 90
minutes followed by reperfusion for periods of up to 6 hours. Compared with
controls, intravenous administration of MSC-EV 30 minutes prior to IRI
dramatically reduced the extent of tissue necrosis, decreased caspase 3-positive
and apoptotic cells, and reduced serum aminotransferase levels. MSC-EV increased
hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains-containing
protein 12, and the chemokine (C-X-C motif) ligand 1, and reduced mRNA expression
of several inflammatory cytokines such as interleukin 6 during IRI. MSC-EV
increased cell viability and suppressed both oxidative injury and nuclear factor
kappa B activity in murine hepatocytes in vitro. In conclusion, the
administration of extracellular vesicles derived from bone marrow-derived MSCs
may ameliorate hepatic IRI by reducing hepatic injury through modulation of the
inflammatory response.Liver Transplantation 23 791-803 2017 AASLD.
PMID- 28407357
TI - The Inhibitory Effect of Nodakenin on Mast-Cell-Mediated Allergic Inflammation
Via Downregulation of NF-kappaB and Caspase-1 Activation.
AB - Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective
for treating function control disorders, bacterial infections, pain, diarrhea,
vitamin E deficiency, and for relaxation of the uterus. The aim of this study was
to investigate the antiallergic related inflammatory effects in phorbol-12
myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast
cells (HMC-1) or anaphylactic activity in a mouse model. Nodakenin inhibited the
mRNA expression and production of pro-inflammatory cytokines such as tumor
necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta in PMACI-stimulated
HMC-1. We also studied the inhibitory effects of nodakenin on the nuclear
translocation of nuclear factor kappa B (NF-kappaB) and activation of caspase-1,
inhibitory kappaB kinase (IKK), and Akt in PMACI-stimulated HMC-1. However,
mitogen-activated protein kinase (MAPK) activation was not sufficient to abrogate
the stimulus. In addition, administration of nodakenin at 20 mg/kg inhibited
histamine release and protected mice against compound 48/80-induced anaphylactic
mortality. Furthermore, Nodakenin inhibited the mRNA expression and production of
pro-inflammatory cytokines and caspase-1 activation in compound 48/80-induced
anaphylactic mice. These results suggest new insight that nodakenin may be a
promising antiallergic related inflammatory agent for inflammatory disorders. J.
Cell. Biochem. 118: 3993-4001, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407358
TI - Vitamin D-related genes are subjected to significant de novo mutation burdens in
autism spectrum disorder.
AB - Vitamin D deficiency is a putative environmental risk factor for autism spectrum
disorder (ASD). Besides, de novo mutations (DNMs) play essential roles in ASD.
However, it remains unclear whether vitamin D-related genes (VDRGs) carry a
strong DNM burden. For the 943 reported VDRGs, we analyzed publicly-available
DNMs from 4,327 ASD probands and 3,191 controls. We identified 126 and 44 loss-of
function or deleterious missense mutations in the probands and the controls,
respectively, representing a significantly higher DNM burden (p = 1.06 * 10-5 ;
odds ratio = 2.11). Specifically, 18 of the VDRGs were found to harbor recurrent
functional DNMs in the probands, compared with only one in the controls. In
addition, we found that 108 VDRGs with functional DNMs in the probands were
significantly more likely to exhibit haploinsufficiency and genic intolerance (p
< 0.0078). These VDRGs were also significantly interconnected and co-expressed,
and also with other known ASD-risk genes (p < 0.0014), thereby forming a
functional network enriched in chromatin modification, transcriptional
regulation, and neuronal function. We provide straightforward genetic evidences
for the first time that VDRGs with a strong degree of DNM burden in ASD and DNMs
of VDRGs could be involved in the mechanism underlying in ASD pathogenesis.
PMID- 28407360
TI - The anterolateral ligament: A cadaveric study in fetuses.
AB - The aim of this study was to determine the presence and morphology of the
anterolateral ligament (ALL) of the knee in a sample of fetuses. We hypothesized
that the ALL is present in sample fetuses and its origin is not related to
repetitive stresses throughout life. Forty fresh-frozen knees from cadaveric
fetuses were dissected using a standard technique. The ALL and other structures
in the anterolateral compartment of the knee were identified. The details of the
femoral and tibial attachments, course and relationships with anatomical
structures of the ALL were identified, recorded, and quantitatively
characterized. The ALL was identified in 100% of the dissected knees. We found
three anatomical patterns regarding the femoral attachment: (1) Proximal and
posterior to the fibular collateral ligament (55%); (2) Together with the fibular
collateral ligament (25%); and (3). Anterior and distal to it (20%). The ALL was
extracapsular with an oblique course attaching into the anterolateral aspect of
the tibia, midway between the midpoint of Gerdy's tubercle and the fibular head.
The ALL has a strong attachment to the lateral meniscus, creating two fascicles:
proximal or meniscofemoral and distal or meniscotibial. The ALL is a constant,
extracapsular anatomical structure in the anterolateral compartment of the knee,
present from the later prenatal period of life. Its morphology shows three
different patterns of femoral attachment in relation to the fibular collateral
ligament position, a strong attachment in the lateral meniscus, and a constant
tibial attachment. Clin. Anat. 30:625-634, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407359
TI - U18666A, an activator of sterol regulatory element binding protein pathway,
modulates presynaptic dopaminergic phenotype of SH-SY5Y neuroblastoma cells.
AB - The therapeutic use of statins has been associated to a reduced risk of
Parkinson's disease (PD) and may hold neuroprotective potential by counteracting
the degeneration of dopaminergic neurons. Transcriptional activation of the
sterol regulatory element-binding protein (SREBP) is one of the major downstream
signaling pathways triggered by the cholesterol-lowering effect of statins. In a
previous study in neuroblastoma cells, we have shown that statins consistently
induce the upregulation of presynaptic dopaminergic proteins and changes of their
function and these effects were accompanied by downstream activation of SREBP. In
this study, we aimed to determine the direct role of SREBP pathway in the
modulation of dopaminergic phenotype. We demonstrate that treatment of SH-SY5Y
cells with U18666A, an SREBP activator, increases the translocation of SREBPs
into the nucleus, increases the expression of SREBP-1, SREBP-2, and of the
presynaptic dopaminergic markers such as vesicular monoamine transporter 2,
synaptic vesicle glycoprotein 2 A and 2 C, synaptogyrin-3, and tyrosine
hydroxylase. The addition of SREBP inhibitor, PF-429242, blocks the increase of
U18666A-induced expression of SREBPs and presynaptic markers. Our results, in
line with previously reported effects of statins, demonstrate that direct
stimulation of SREBP translocation is associated to differentiation toward a
dopaminergic-like phenotype and suggest that SREBP-mediated transcriptional
activity may lead to the restoration of the presynaptic dopamine markers and may
contribute to neuroprotection of dopaminergic neurons. These findings further
support the potential protective role of statin in PD and shed light upon SREBP
as a potential new target for developing disease-modifying treatment in PD.
PMID- 28407362
TI - Traffic-related air pollution and lung cancer: A meta-analysis.
PMID- 28407361
TI - Influence of Tanshinone IIA on apoptosis of human esophageal carcinoma Eca-109
cells and its molecular mechanism.
AB - BACKGROUND: Previous studies have shown that Tanshinone (Tan) IIA exerts obvious
antitumor efficacy; however, its molecular mechanism remains unclear. This study
was conducted to identify the influence of Tan IIA on Eca-109 cell apoptosis,
explore its molecular mechanism, and provide a theoretical basis for clinical
application. METHODS: Eca-109 cells were cultured in vitro and treated with
different concentrations of Tan IIA. Morphologic changes were viewed under
inverted fluorescence microscope with dual acridine orange/ethidium bromide
staining assay. Methyl-thiazolyl-tetrazolium and Annexin V propidium iodide
assays were respectively used to measure cell viability and apoptosis rate. The
protein and messenger (m)RNA expression of binding immunoglobulin protein (BIP),
mitochondrial cytochrome c (CytC), and caspase-9 were detected by Western blot
and quantitative real-time PCR, respectively. RESULTS: Cell viability decreased
and the apoptosis rate significantly increased with increasing concentrations of
Tan IIA (0, 20, 40, 60 MUg/mL), which indicated that Tan IIA inhibited the
proliferation and induced the apoptosis of Eca-109 cells in a dose-dependent
manner. Eca-109 cells treated with 60 MUg/mLTan IIA showed typical morphological
changes of apoptosis under the inverted microscope. Moreover, compared with the
negative control group, protein and mRNA expression of BIP decreased
significantly (P < 0.05), whereas protein and mRNA expression of CytC and caspase
9 increased significantly (P < 0.05). CONCLUSION: Tan IIA can induce apoptosis in
human esophageal carcinoma Eca-109 cells by regulating BIP, CytC, and caspase-9
expression. Endoplasmic reticulum stress and mitochondrial-dependent may be
involved in Tan IIA-induced Eca-109 cell apoptosis.
PMID- 28407363
TI - De novo unbalanced translocation (4p duplication/8p deletion) in a patient with
autism, OCD, and overgrowth syndrome.
AB - Chromosomal abnormalities, such as unbalanced translocations and copy number
variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al.
(2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub
microscopic genomic deletions and duplications, are missed by G-banded
karyotyping or Fragile X screening alone and are picked up by chromosomal
microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations
involving chromosomes 4 and 8 are possibly the second most frequent translocation
in humans and are often undetected in routine cytogenetics [Giglio et al. (2002)
Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf
Hirschhorn syndrome while 4p16 duplications have been associated with an
overgrowth syndrome and mild to moderate mental retardation [Partington et al.
(1997) Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the
autism candidate gene DLGAP2, which can contribute to autism when disrupted
[Marshall et al. (2008) The American Journal of Human Genetics 82: 477-488] .
There has been a case report of a family with autism spectrum disorder (ASD),
prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p
(16;23) [Partington et al. (1997)]. This is an independent report of a male
patient with autism, obsessive compulsive disorder (OCD), attention-deficit
hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo
unbalanced translocation der (8) t (4;8) p (16.1->ter; 23.1->ter) was initially
missed by routine cytogenetics but detected with SNP microarray, allowing higher
resolution of translocation breakpoints.
PMID- 28407364
TI - Identification of a conserved 8 aa insert in the PIP5K protein in the
Saccharomycetaceae family of fungi and the molecular dynamics simulations and
structural analysis to investigate its potential functional role.
AB - Homologs of the phosphatidylinositol-4-phosphate-5-kinase (PIP5K), which controls
a multitude of essential cellular functions, contain a 8 aa insert in a conserved
region that is specific for the Saccharomycetaceae family of fungi. Using
structures of human PIP4K proteins as templates, structural models were generated
of the Saccharomyces cerevisiae and human PIP5K proteins. In the modeled S.
cerevisiae PIP5K, the 8 aa insert forms a surface exposed loop, present on the
same face of the protein as the activation loop of the kinase domain.
Electrostatic potential analysis indicates that the residues from 8 aa conserved
loop form a highly positively charged surface patch, which through electrostatic
interaction with the anionic portions of phospholipid head groups, is expected to
play a role in the membrane interaction of the yeast PIP5K. To unravel this
prediction, molecular dynamics (MD) simulations were carried out to examine the
binding interaction of PIP5K, either containing or lacking the conserved
signature insert, with two different membrane lipid bilayers. The results from MD
studies provide insights concerning the mechanistic of interaction of PIP5K with
lipid bilayer, and support the contention that the identified 8 aa conserved
insert in fungal PIP5K plays an important role in the binding of this protein
with membrane surface. Proteins 2017; 85:1454-1467. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28407365
TI - Role of allopregnanolone biosynthesis in acute stress-induced anxiety-like
behaviors in mice.
AB - The neurosteroid allopregnanolone (3alpha, 5alpha-tetra-hydroprogesterone: ALLO)
elicits anxiolytic, anticonvulsant, and hypnotic anesthetic effects in vivo
similar to those induced by other positive allosteric modulators of the GABAA
receptor. Endogenous ALLO has been shown to be rapidly elevated in the brain by
acute stress paradigms, such as immobilization, in animal models. The present
study was designed to ascertain the role of neurosteroid biosynthesis in the
anxiety-like behavior induced by immobilization stress. Mice were exposed to an
immobilization stressor for 2 h. After 24 h, the mice that had been immobilized
did not behave significantly differently in the elevated plus maze (EPM) test and
in the elevated open platform (EOP) test than the mice that had not been
immobilized. In contrast, finasteride-pretreated immobilization stressed mice did
behave significantly differently in the EPM and EOP tests. These findings suggest
that ALLO biosynthesis contributes to stress resistance. Furthermore, the ALLO
mimetic drug alfaxalone appeared to antagonize the effects of finasteride by
significantly changing the behavior in the EPM test or in the EOP test in
finasteride (10 mg kg-1 )-pretreated immobilized mice. In addition, alfaxalone,
unlike diazepam, did not affect the muscle tone of the mice, as measured by the
grip strength test. These results suggest that alfaxalone is a promising
anxiolytic candidate lacking benzodiazepine-like muscle-relaxant effects.
PMID- 28407366
TI - Screening children for pulmonary arteriovenous malformations: Evaluation of 18
years of experience.
AB - BACKGROUND: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant
disease with multi-systemic vascular dysplasia. Early diagnosis through screening
is important to prevent serious complications. How best to screen children of
affected parents for pulmonary arteriovenous malformations (PAVMs) is often
subject to debate. Transthoracic contrast echocardiogram (TTCE) is considered
optimal in screening for PAVMs in adults. Guidelines for the screening of
children are not specific, reflecting the lack of scientific evidence on the best
method to use. OBJECTIVE: Aims of this study are (i) to evaluate our current
screening method, consisting of history, physical examination, pulse oximetry,
and chest radiography and (ii) to assess whether postponing more invasive
screening for PAVMs until adulthood is safe. METHODS: This is a prospective
observational cohort study using a patient database. RESULTS: Over a period of 18
years (mean follow-up 9.21 years, SD 4.72 years), 436 children from HHT families
were screened consecutively. A total of 175/436 (40%) children had a diagnosis of
HHT. PAVMs were detected in 39/175 (22%) children, 33/39 requiring treatment by
embolotherapy. None of the screened children suffered any PAVM-associated
complications with this screening method. CONCLUSION: This study shows that a
conservative screening method during childhood is sufficient to detect large
PAVMs and protect children with HHT for PAVM-related complications. Postponing
TTCE and subsequent chest CT scanning until adulthood to detect any smaller PAVMs
does not appear to be associated with major risk.
PMID- 28407367
TI - A review of early influences on physical activity and sedentary behaviors of
preschool-age children in high-income countries.
AB - PURPOSE: Promoting physical activity (PA) is a key component of preventing and
controlling childhood obesity. Despite well-documented benefits of PA, globally,
rates of PA among young children have declined over the past decades, and most
children are not accruing sufficient PA daily. Helping children develop the
foundation for PA habits early in life is critical for the promotion of health in
childhood and prevention of chronic diseases later in life, and will ultimately
promote longer and healthier lives for individuals and the general population.
The purpose of this review is to provide a synthesis of current evidence on
influences on PA and sedentary behaviors of preschool-age children in high-income
countries. DESIGN AND METHODS: A systematic review of three databases was
performed. Studies conducted in high-income countries and published from 2000
onward that addressed influences on PA and sedentary behaviors of preschool-age
children were identified and reviewed. Additionally, reference lists of
identified articles and relevant published reviews were reviewed. Studies that
met the following inclusion criteria were considered: (a) sample included
preschoolers (age <=5 years); (b) PA and/or sedentary behaviors or factors
associated with PA and/or sedentary behaviors was assessed; (c) published in
English; (d) used either quantitative or qualitative methods; and (e) conducted
in a high-income country. Data were extracted from selected studies to identify
influences on PA and sedentary behaviors of preschool-age children and organized
using the social-ecological model according to multiple levels of influence.
RESULTS: Results from included studies identify multiple factors that influence
PA and sedentary behaviors of young children in high-income countries at the
various levels of the social-ecological model including intrapersonal,
interpersonal, environmental, organizational, and policy. PRACTICE IMPLICATIONS:
Given pediatric nurses' role as primary care providers, and their frequent and
continued contact with parents and their children throughout childhood through
well-child visits, immunization, and minor acute illnesses, they are well
positioned to promote and support the development of early healthful PA habits of
children starting in early childhood.
PMID- 28407368
TI - Association of body weight with efficacy and safety outcomes in phase III
randomized controlled trials of direct oral anticoagulants: a systematic review
and meta-analysis.
AB - Essentials The association of body weight and patient-important outcomes remains
unknown. Phase III randomized controlled trials of direct oral anticoagulants
(DOACs) were searched. Risk of outcomes varying among body weight subgroups is
not attributable to anticoagulant type. Dose adjustment of DOACs, outside that
recommended, is unlikely to improve the outcomes. Click to hear Dr Braunwald's
perspective on antithrombotic therapy in cardiovascular disease SUMMARY:
Background Concerns have arisen in direct oral anticoagulant (DOAC)-treated
patients about safety and efficacy in extremes of body weight. The aims of this
systematic review were to investigate the association of body weight and patient
important outcomes in patients treated with DOACs or warfarin, and to demonstrate
the fixed-dose effect of DOACs. Methods MEDLINE and EMBASE were searched until
November 2016. Phase III randomized controlled trials (RCTs) using DOACs in
atrial fibrillation (AF) and acute venous thromboembolism (VTE) were included.
Relative risk and 95% confidence interval were calculated. The pooled estimates
were performed using a Mantel-Haenszel random effects model. Results A total of
11 phase III RCTs were included. Low body weight was associated with increased
risk of thromboembolism compared with non-low body weight (relative risk [RR],
1.57; 95% confidence interval [CI], 1.34-1.85). High body weight was not
associated with risk of thromboembolism compared with non-high body weight (RR,
0.88; 95% CI, 0.63-1.23). The subgroup of AF patients with high body weight had a
lower risk of thromboembolism compared with non-high body weight (RR, 0.43; 95%
CI, 0.28-0.67). Bleeding outcomes were comparable for all body weight
comparisons. There were no clear interactions between types of anticoagulant in
all outcomes. Conclusion The pooled effect of both the DOAC and comparison arms
was likely to be attributable to differences in baseline thrombotic risk in each
body weight category, rather than an effect of the type or dose of DOAC used for
each indication. Dose adjustment of DOACs, outside that recommended in the
package insert, is unlikely to improve safety or efficacy.
PMID- 28407369
TI - Reactivity of Functionalized Ynamides with Tetracyanoethylene: Scope, Limitations
and Optoelectronic Properties of the Adducts.
AB - The reactivity of functionalized ynamides and arylynamines with
tetracyanoethylene at room temperature was evaluated. In most cases, the
corresponding 1,1,4,4-tetracyanobutadienes (TCBDs) were obtained in good to
excellent yields through a [2+2]-cycloaddition/[2+2]-retro-electrocyclization
sequence. The influence of diverse functional groups on the yield of the reaction
was investigated, in particular concerning multiple ynamides. These TCBDs were
characterized by various spectroscopic techniques and electrochemistry and X-ray
diffraction in some cases.
PMID- 28407370
TI - Inflammation-Triggered Cancer Immunotherapy by Programmed Delivery of CpG and
Anti-PD1 Antibody.
PMID- 28407371
TI - Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis
of glycated hemoglobin via ion-exchange high-performance liquid chromatography.
AB - BACKGROUND: To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and alpha
thalassemia HbH on the results of HbA1c assessment using ion-exchange high
performance liquid chromatography (IE-HPLC). METHODS: We enrolled five patients
in which the results of the IE-HPLC HbA1c assay were inconsistent with the
average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis
using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy
mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA
HPLC) and turbidimetric inhibition immunoassay (TINIA). RESULTS: Two patients had
the HbJ Bangkok variant. Hb genotypes of these patients were beta41-42 /betaJ
Bangkok and betaN /betaJ Bangkok , and the content of HbJ Bangkok was 93.9% and
52.4%, respectively. The remaining three patients had the following: HbE (betaN
/betaE Hb genotype, 23.6% HbE content), HbG Taipei (betaN /betaG Taipei Hb
genotype, 39.4% HbG Taipei content), and alpha-thalassemia HbH (6.1% HbH content,
2.8% Hb Bart's content). In the patients with beta-thalassemia and HbJ Bangkok
variants, the presence of the variants interfered with the results of HbA1c
analyses using IE-HPLC and TINIA; in the remaining four patients, there was
interference with the results of HbA1c IE-HPLC but not with the TINIA assay.
There was no interference with BA-HPLC HbA1c results. CONCLUSIONS: HbJ Bangkok,
HbE, HbG Taipei Hb, and alpha-thalassemia HbH disease cause varying degrees of
interference with the analysis of HbA1c using IE-HPLC. In these patients, we
suggest using methods free from such interference for the analysis of HbA1c and
other indicators to monitor blood glucose levels.
PMID- 28407372
TI - Serum macrophage migration inhibitory factor is correlated with atrial
fibrillation.
AB - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory
cytokine secreted by macrophages. This study is performed to investigate whether
serum MIF is correlated with atrial fibrillation (AF). METHODS: Totally, 186 AF
patients and 103 healthy controls were enrolled in this study. AF patients were
then divided into paroxysmal AF, persistent AF, and permanent AF subgroups.
RESULTS: There were higher serum MIF concentrations in AF patients than in
healthy subjects. Logistic regression analysis demonstrated that serum MIF was
associated with AF. Permanent AF patients exhibited higher serum MIF
concentrations than persistent and paroxysmal AF subgroups. Elevated serum MIF
concentrations were found in persistent AF patients compared with paroxysmal AF
patients. Moreover, serum MIF concentrations were associated with left atrial
diameter after Spearman correlation analysis.
PMID- 28407373
TI - Activation of the Arabidopsis membrane-bound transcription factor bZIP28 is
mediated by site-2 protease, but not site-1 protease.
AB - The unfolded protein response (UPR) is a homeostatic cellular response conserved
in eukaryotic cells to alleviate the accumulation of unfolded proteins in the
endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription
factor activated by proteolytic cleavage in response to ER stress, thereby
releasing its cytosolic portion containing the bZIP domain from the membrane to
translocate into the nucleus where it induces the transcription of genes encoding
ER-resident molecular chaperones and folding enzymes. It has been widely
recognized that the proteolytic activation of bZIP28 is mediated by the
sequential cleavage of site-1 protease (S1P) and site-2 protease (S2P). In the
present study we provide evidence that bZIP28 protein is cleaved by S2P, but not
by S1P. We demonstrated that wild-type and s1p mutant plants produce the active,
nuclear form of bZIP28 in response to the ER stress inducer tunicamycin. In
contrast, tunicamycin-treated s2p mutants do not accumulate the active, nuclear
form of bZIP28. Consistent with these observations, s2p mutants, but not s1p
mutants, exhibited a defective transcriptional response of ER stress-responsive
genes and significantly higher sensitivity to tunicamycin. Interestingly, s2p
mutants accumulate two membrane-bound bZIP28 fragments with a shorter ER lumen
facing C-terminal domain. Importantly, the predicted cleavage sites are located
far from the canonical S1P recognition motif previously described. We propose
that ER stress-induced proteolytic activation of bZIP28 is mediated by the
sequential actions of as-yet-unidentified protease(s) and S2P, and does not
require S1P.
PMID- 28407374
TI - Regional cerebral hyperperfusion: A biomarker of upcoming stroke-like episodes?
PMID- 28407376
TI - Thermoresponsive Emission Switching via Lower Critical Solution Temperature
Behavior of Organic-Inorganic Perovskite Nanoparticles.
AB - Lead halide perovskites have shown much promise for high-performing solar cells
due to their inherent electronic nature, and though the color of bright-light
emitters based on perovskite nanoparticles can be tuned by halide mixing and/or
size control, dynamic switching using external stimuli remains a challenge. This
article reports an unprecedented lower critical solution temperature (LCST) for
toluene solutions containing methylammonium lead bromide (MAPbBr3 ), oleic acid,
alkylamines, and dimethylformamide. The delicate interplay of these molecules and
ions allows for the reversible formation and decomposition of MAPbBr3
nanoparticles upon heating and cooling, which is accompanied by green and blue
photoemissions at each state. An intermediate 1D crystal with PbBr2 -amine
coordination is found to play pivotal role in this, and a mechanistic insight is
provided based on a three-state model. In addition to a high quantum yield (up to
85%), this system allows for control over the cloud point (30-80 degrees C)
through compositional engineering and the luminescent color (blue to red) via
halogen exchange, thus making it a versatile solution for developing functional
molecular organic-inorganic LCST quantum dots.
PMID- 28407375
TI - H19 promotes cholestatic liver fibrosis by preventing ZEB1-mediated inhibition of
epithelial cell adhesion molecule.
AB - : Based on our recent finding that disruption of bile acid (BA) homeostasis in
mice results in the induction of hepatic long noncoding RNA H19 expression, we
sought to elucidate the role of H19 in cholestatic liver fibrosis. Hepatic
overexpression of H19RNA augmented bile duct ligation (BDL)-induced liver
fibrosis, which was accompanied by the elevation of serum alanine
aminotransferase, aspartate aminotransferase, bilirubin, and BA levels. Multiple
genes related to liver fibrosis, inflammation, and biliary hyperplasia were
increased in H19-BDL versus null-BDL mice, whereas genes in BA synthesis were
decreased. Livers and spleens of H19-BDL mice showed significant enrichment of
CD3+gammadelta+, interleukin-4, and interleukin-17 producing CD4+ and CD8+ immune
cell populations. H19 down-regulated hepatic zinc finger E-box-binding homeobox 1
(ZEB1) but up-regulated epithelial cell adhesion molecule (EpCAM) and SRY (sex
determining region Y)-box 9 expression. Mechanistically, ZEB1 repressed EpCAM
promoter activity and gene transcription. H19RNA impeded ZEB1's inhibitory action
by interacting with ZEB1 protein to prevent its binding to the EpCAM promoter.
Hepatic overexpression of ZEB1 or knockdown of EpCAM diminished H19-induced
fibrosis; the latter was also prevented in H19-/- mice. H19RNA was markedly
induced by bile acids in mouse small cholangiocytes and to a lesser extent in
mouse large cholangiocytes. The up-regulation of H19RNA and EpCAM correlated
positively with the down-regulation of ZEB1 in primary sclerosing cholangitis and
primary biliary cirrhosis liver specimens. CONCLUSION: The activation of hepatic
H19RNA promoted cholestatic liver fibrosis in mice through the ZEB1/EpCAM
signaling pathway. (Hepatology 2017;66:1183-1196).
PMID- 28407377
TI - Biomarkers of microvascular endothelial dysfunction predict incident dementia: a
population-based prospective study.
AB - BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of
neurodegenerative diseases. Whether biomarkers of microvascular endothelial
dysfunction can predict dementia is largely unknown. We explored the longitudinal
association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal
endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with
dementia and subtypes amongst community-dwelling older adults. METHODS: A
population-based cohort of 5347 individuals (men, 70%; age, 69 +/- 6 years)
without prevalent dementia provided plasma for determination of MR-proANP, CT
proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were
diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68
other aetiology) over a period of 4.6 +/- 1.3 years. Relations between baseline
biomarker plasma concentrations and incident dementia were assessed using
multivariable Cox regression analysis. RESULTS: Higher levels of MR-proANP were
significantly associated with increased risk of all-cause and vascular dementia
(hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P =
0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia
increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145
1681 pmol L-1 vs. Q1, 22-77 pmol L-1 : HR: 1.83; 95%CI: 1.23-2.71) and was most
pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14
6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular
dementia with a cut-off value at 68 pmol L-1 (Q3-Q4, 68-432 pmol L-1 vs. Q1-Q2,4
68 pmol L-1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated
no increased risk of developing dementia after adjustment for traditional risk
factors. CONCLUSIONS: Elevated plasma concentration of MR-proANP is an
independent predictor of all-cause and vascular dementia. Pronounced increase in
CT-proET-1 indicates higher risk of vascular dementia.
PMID- 28407378
TI - New Ether-functionalized Morpholinium- and Piperidinium-based Ionic Liquids as
Electrolyte Components in Lithium and Lithium-Ion Batteries.
AB - Here, two ionic liquids, N-ethoxyethyl-N-methylmorpholinium
bis(trifluoromethanesulfonyl)imide (M1,2O2 TFSI) and N-ethoxyethyl-N
methylpiperidinium bis(trifluoromethanesulfonyl)imide (P1,2O2 TFSI) were
synthesized and compared. Fundamental relevant properties, such as thermal and
electrochemical stability, density, and ionic conductivity were analyzed to
evaluate the effects caused by the presence of the ether bond in the side chain
and/or in the organic cation ring. Upon lithium salt addition, two electrolytes
suitable for lithium batteries applications were found. Higher conducting
properties of the piperidinium-based electrolyte resulted in enhanced cycling
performances when tested with LiFePO4 (LFP) cathode in lithium cells. When mixing
the P1,2O2 TFSI/LiTFSI electrolyte with a tailored alkyl carbonate mixture, the
cycling performance of both Li and Li-ion cells greatly improved, with prolonged
cyclability delivering very stable capacity values, as high as the theoretical
one in the case of Li/LFP cell configurations.
PMID- 28407379
TI - Epithelial-mesenchymal plasticity and circulating tumor cells: Travel companions
to metastases.
AB - Epithelial-mesenchymal transitions (EMTs) associated with metastatic progression
may contribute to the generation of hybrid phenotypes capable of plasticity. This
cellular plasticity would provide tumor cells with an increased potential to
adapt to the different microenvironments encountered during metastatic spread.
Understanding how EMT may functionally equip circulating tumor cells (CTCs) with
an enhanced competence to survive in the bloodstream and niche in the colonized
organs has thus become a major cancer research axis. We summarize here clinical
data with CTC endpoints involving EMT. We then review the work functionally
linking EMT programs to CTC biology and deciphering molecular EMT-driven
mechanisms supporting their metastatic competence. Developmental Dynamics 247:432
450, 2018. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407380
TI - N-glycan maturation mutants in Lotus japonicus for basic and applied glycoprotein
research.
AB - Studies of protein N-glycosylation are important for answering fundamental
questions on the diverse functions of glycoproteins in plant growth and
development. Here we generated and characterised a comprehensive collection of
Lotus japonicusLORE1 insertion mutants, each lacking the activity of one of the
12 enzymes required for normal N-glycan maturation in the glycosylation
machinery. The inactivation of the individual genes resulted in altered N-glycan
patterns as documented using mass spectrometry and glycan-recognising antibodies,
indicating successful identification of null mutations in the target glyco-genes.
For example, both mass spectrometry and immunoblotting experiments suggest that
proteins derived from the alpha1,3-fucosyltransferase (Lj3fuct) mutant completely
lacked alpha1,3-core fucosylation. Mass spectrometry also suggested that the
Lotus japonicus convicilin 2 was one of the main glycoproteins undergoing
differential expression/N-glycosylation in the mutants. Demonstrating the
functional importance of glycosylation, reduced growth and seed production
phenotypes were observed for the mutant plants lacking functional mannosidase I,
N-acetylglucosaminyltransferase I, and alpha1,3-fucosyltransferase, even though
the relative protein composition and abundance appeared unaffected. The strength
of our N-glycosylation mutant platform is the broad spectrum of resulting
glycoprotein profiles and altered physiological phenotypes that can be produced
from single, double, triple and quadruple mutants. This platform will serve as a
valuable tool for elucidating the functional role of protein N-glycosylation in
plants. Furthermore, this technology can be used to generate stable plant mutant
lines for biopharmaceutical production of glycoproteins displaying relative
homogeneous and mammalian-like N-glycosylation features.
PMID- 28407381
TI - Arrival of rabbit haemorrhagic disease virus 2 to northern Europe: Emergence and
outbreaks in wild and domestic rabbits (Oryctolagus cuniculus) in Sweden.
AB - Incursion of rabbit haemorrhagic disease virus (RHDV) into Sweden was documented
in 1990 and it is now considered endemic in wild rabbit (Oryctolagus cuniculus)
populations. Rabbit haemorrhagic disease virus 2 (RHDV2), a new, related
lagovirus was first detected in France in 2010, and has spread rapidly throughout
Europe and beyond. However, knowledge of RHDV2 in northern Europe is sporadic and
incomplete, and in Sweden, routinely available diagnostic methods to detect
rabbit haemorrhagic disease (RHD) do not distinguish between types of virus
causing disease. Using RHDV2-specific RT-qPCR, sequencing of the VP60 gene and
immunological virus typing of archived and prospective case material from the
National Veterinary Institute's (SVA) wildlife disease surveillance programme and
diagnostic pathology service, we describe the emergence of RHDV2 in Sweden in
both wild and domestic rabbits. The earliest documented outbreak occurred on 22
May 2013, and from May 2013 to May 2016, 10 separate incidents of RHDV2 were
documented from six different municipalities in the southern half of Sweden.
Phylogenetic analysis of the VP60 gene shows clear clustering of Swedish isolates
into three separate clusters within two different clades according to geographic
location and time, suggesting viral evolution, multiple introduction events or
both. Almost all cases of RHD examined by SVA from May 2013 to May 2016 were
caused by RHDV2, suggesting that RHDV2 may be replacing RHDV as the predominant
cause of RHD in Sweden.
PMID- 28407382
TI - Carbohydrate uptake in Advenella mimigardefordensis strain DPN7T is mediated by
periplasmic sugar oxidation and a TRAP-transport system.
AB - In this study, we investigated an SBP (DctPAm ) of a tripartite ATP-independent
periplasmic transport system (TRAP) in Advenella mimigardefordensis strain DPN7T
. Deletion of dctPAm as well as of the two transmembrane compounds of the
tripartite transporter, dctQ and dctM, impaired growth of A. mimigardefordensis
strain DPN7T , if cultivated on mineral salt medium supplemented with d-glucose,
d-galactose, l-arabinose, d-fucose, d-xylose or d-gluconic acid, respectively.
The wild type phenotype was restored during complementation studies of A.
mimigardefordensis DeltadctPAm using the broad host vector pBBR1MCS-5::dctPAm .
Furthermore, an uptake assay with radiolabeled [14 C(U)]-d-glucose clearly showed
that the deletion of dctPAm , dctQ and dctM, respectively, disabled the uptake of
this aldoses in cells of either mutant strain. Determination of KD performing
thermal shift assays showed a shift in the melting temperature of DctPAm in the
presence of d-gluconic acid (KD 11.76 +/- 1.3 uM) and the corresponding aldonic
acids to the above-mentioned carbohydrates d-galactonate (KD 10.72 +/- 1.4 uM), d
fuconic acid (KD 13.50 +/- 1.6 uM) and d-xylonic acid (KD 8.44 +/- 1.0 uM). The
sugar (glucose) dehydrogenase activity (E.C.1.1.5.2) in the membrane fraction was
shown for all relevant sugars, proving oxidation of the molecules in the
periplasm, prior to transport.
PMID- 28407383
TI - MSH1 maintains organelle genome stability and genetically interacts with RECA and
RECG in the moss Physcomitrella patens.
AB - Chloroplast and mitochondrial DNA encodes genes that are essential for
photosynthesis and respiration, respectively. Thus, loss of integrity of the
genomic DNA of organelles leads to a decline in organelle function and alteration
of organelle genetic information. RECA (RECA1 and RECA2) and RECG, which are
homologs of bacterial homologous recombination repair (HRR) factors RecA and
RecG, respectively, play an important role in the maintenance of integrity of the
organelle genome by suppressing aberrant recombination between short dispersed
repeats (SDRs) in the moss Physcomitrella patens. On the other hand, MutS homolog
1 (MSH1), a plant-specific MSH with a C-terminal GIY-YIG endonuclease domain, is
involved in the maintenance of integrity of the organelle genome in the
angiosperm Arabidopsis thaliana. Here, we address the role of the duplicated MSH1
genes, MSH1A and MSH1B, in P. patens, in which MSH1A lacks the C-terminal
endonuclease domain. MSH1A and MSH1B localized to both chloroplast and
mitochondrial nucleoids in protoplast cells. Single and double knockout (KO)
mutants of MSH1A and MSH1B showed no obvious morphological defects; however,
MSH1B KO and double KO mutants, as well as MSH1B GIY-YIG deletion mutants,
exhibited genomic instability due to recombination between SDRs in chloroplasts
and mitochondria. Creating double KO mutations of each combination of MSH1B,
RECA2 and RECG synergistically increased recombination between SDRs in
chloroplasts and mitochondria. These results show the role of MSH1 in the
maintenance of integrity of the organelle genome and the genetic interaction
between MSH1 and homologs of HRR factors in the basal land plant P. patens.
PMID- 28407384
TI - Point mutations in acetylcholinesterase 1 associated with chlorpyrifos resistance
in the brown planthopper, Nilaparvata lugens Stal.
AB - Insecticide resistance frequently results from target-site insensitivity, such as
point mutations in acetylcholinesterases (AChEs) for resistance to
organophosphates and carbamates. From a field-originated population of
Nilaparvata lugens, a major rice pest, a resistant population (R9) was obtained
by nine-generation continuous selection with chlorpyrifos. From the same field
population, a relatively susceptible population (S9) was also constructed through
rearing without any insecticides. Compared to the susceptible strain, Sus [medium
lethal dose (LC50 ) = 0.012 mg/l], R9 had a resistance ratio (RR) of 253.08-fold,
whereas the RR of S9 was only 2.25-fold. Piperonyl butoxide and triphenyl
phosphate synergized chlorpyrifos in R9 less than three-fold, indicating other
important mechanisms for high resistance. The target-site insensitivity was
supported by the key property differences of crude AChEs between R9 and S9.
Compared to S9, three mutations (G119S, F331C and I332L) were detected in NlAChE1
from individuals of the R9 and field populations, but no mutation was detected in
NlAChE2. G119S and F331C could decreased insecticide sensitivities in recombinant
NlAChE1, whereas I332L took effect through increasing the influence of F331C on
target insensitivity. F331C might be deleterious because of its influence on the
catalytic efficiency of NlAChE1, whereas I332L would decrease these adverse
effects and maintain the normal functions of AChEs.
PMID- 28407386
TI - The predictive value of ePAQ in the urodynamic diagnoses-A prospective cohort
study.
AB - AIMS: To assess whether the electronic Personal Assessment Questionnaire-Pelvic
Floor (ePAQ-PF) had accuracy in predicting the urodynamic diagnoses of Detrusor
Overactivity (DO) and/or Urodynamic Stress Incontinence (USI). METHODS: Tertiary
urogynaecology unit linked to an academic university teaching hospital.
Consecutive women who presented with lower urinary tract symptoms (LUTS) and were
booked to have urodynamic studies. Women completed an ePAQ-PF prior to having
urodynamics (UDS) by clinicians who were blinded to the ePAQ-PF results while
conducting this procedure. Receiver Operating Characteristics (ROC) curves were
constructed for predictive accuracy of overactive bladder (OAB) score in DO and
of stress urinary incontinence (SUI) score in USI. Prospective cohort study
designed to meet the requirements of the standards for reporting of diagnostic
accuracy (STARD). RESULTS: 390 women with a mean age of 54.2 (range 21-92) years
were recruited. The majority (n = 294; 75%) were White Caucasian and had two
children (n = 157; 40.3%). Of them, 67.2% (n = 262) had DO and USI was confirmed
in 21.5% (n = 84). The area under the ROC curve for DO was 0.704 (95% confidence
interval 0.650-0.759) and for USI it was 0.731 (95% confidence interval 0.652
0.778). CONCLUSIONS: The OAB and SUI scores on the ePAQ-PF demonstrated that they
are fair predictors in diagnosing DO and USI. As the OAB and SUI score on ePAQ-PF
increased so did the likelihood of DO (up to a score of 75) and USI on UDS.
PMID- 28407385
TI - Effect of formalin fixation and tumour size in small-sized non-small-cell lung
cancer: a prospective, single-centre study.
AB - AIMS: Formalin fixation can cause tumour shrinkage. The aim of this study was to
prospectively evaluate the effect of overnight formalin fixation on tumour size
and the effect of clinicopathological parameters on changes in tumour size in
small-sized non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: Our study
included 126 surgically resected NSCLC specimens submitted in a fresh state. We
measured the largest cross-sectional tumour diameters in the fresh and formalin
fixed specimens. Tumour size significantly differed (mean, 0.66 mm; P < 0.001)
and was positively correlated (r2 = 0.982; P < 0.001) between fresh and formalin
fixed specimens. The percentage difference after fixation was 4.06%. Formalin
fixation caused tumour shrinkage in 46.8%, tumour enlargement in 4.8%, and a
tumour stage shift in 3.17%. The risk of a > 10% change in tumour size after
formalin fixation was increased in tumours with a lepidic pattern [odds ratio
(OR): 6.268; P = 0.001], in subsolid tumours (OR: 4.068; P = 0.011), and in the
presence of adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA)
histology (OR: 6.545; P = 0.003). Pleural dimpling lowered the risk of tumour
size change after fixation (OR: 0.162; P = 0.019). On multivariate analysis, a
lepidic pattern (OR: 4.601; P = 0.010) and AIS/MIA histology (OR: 4.381; P =
0.026) were still significant risk factors. Longer ischaemic time was the single
risk factor for tumour shrinkage in the invasive adenocarcinoma subgroup (OR:
5.357; P = 0.021). CONCLUSION: NSCLC tumours shrank or enlarged by 4.06% after
overnight formalin fixation. A lepidic pattern and AIS/MIA histology were
independent risk factors for both significant tumour shrinkage and growth after
fixation. Longer ischaemic time was the single risk factor for significant tumour
shrinkage in invasive adenocarcinoma.
PMID- 28407387
TI - Gigging Benzene.
AB - Go Aggies! Go Chemikers! The word "gig" applies to a multipronged metal tool for
hunting frogs and fish. It constitutes part of a rallying cry, "gig 'em" that
inspires Texas A&M Aggies to victory in athletic and academic competitions. This
Highlight examines recent victories in the C....._ C cleavage of benzene made
possible by a four-pronged iridium gig that yields a "spring-loaded"
norbornadiene-like structure with significant ring strain.
PMID- 28407388
TI - Iridium-Catalyzed Regio- and Enantioselective Hydroarylation of Alkenyl Ethers by
Olefin Isomerization.
AB - Iridium-catalyzed hydroarylation of alkenyl ethers, such as allylic and
homoallylic ethers, by C-H bond activation gave high yields of the corresponding
addition products, where the aryl groups were selectively installed at the alpha
carbon atom to the alkoxy group. The reaction involves an isomerization of the
alkenyl ethers into the corresponding 1-alkenyl ethers, which then undergo the
regio- and enantioselective hydroarylation.
PMID- 28407389
TI - The therapeutic role of mental health nurses in psychiatric intensive care: A
mixed-methods investigation in an inner-city mental health service.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Mental health services have been radically
transformed since the 1990s, with an emphasis on care in the community. However,
acute psychiatric wards remain an important component of service provision.
Research shows that patients receive limited therapeutic interaction with nurses
in such settings. A recent review showed that just 4%-12% of nurses' time was
spent on activities that could be considered therapeutic. WHAT THIS STUDY ADDS TO
EXISTING KNOWLEDGE?: Whereas nurses wanted more time for individual therapeutic
activity, patients were content with brief interactions. However, such contact
was not always available, partly due to workload pressures. Both nurses and
patients believed that a collaborative approach, involving the whole
multidisciplinary team, was key to the success of therapeutic engagement. The
meaning of therapeutic engagement remains nebulous. WHAT ARE THE IMPLICATIONS FOR
PRACTICE?: Nurse education, ward management and clinical supervision should have
greater emphasis on therapeutic engagement. Further research is needed to develop
therapeutic engagement in acute psychiatric settings; such work should involve
patients as active and equal partners. ABSTRACT: Introduction Despite indications
that therapeutic interaction is beneficial for patients and for nurses' job
satisfaction in acute psychiatric care, research shows a small amount of nurses'
time is spent on such activity. Aims This study investigated the actual and
potential therapeutic role of the mental health nurse in psychiatric intensive
care, where admission is due to violence or aggression. Methods In a mixed
methods concurrent triangulation design, clinician and patient activity was
observed using a structured measurement tool, and qualitative interviews were
conducted with four practitioners and six patients. Findings were generated using
thematic analysis and descriptive statistics. Results Of the directly observed
234 clinician and 309 patient activities, 20.9% and 15.9%, respectively, were
classified as therapeutic engagement. Interviews revealed that both clinicians
and patients wanted more therapeutic contact, but whereas nurses wanted longer
time to spend in individual sessions, patients preferred brief but more frequent
interaction with nurses. Discussion This study shows disparity between actual and
desirable levels of therapeutic interaction. Apart from organizational
constraints, a fundamental problem is the lack of definition or established
practices of therapeutic engagement. Implications for Practice There should be
more emphasis on therapeutic engagement in nurse education, ward management and
clinical supervision.
PMID- 28407390
TI - Enantioselective Chemo- and Biocatalysis: Partners in Retrosynthesis.
AB - Recent developments of stereoselective biocatalytic and chemocatalytic methods
are discussed. The review provides a guide to the use of biocatalytic methods in
the area of chemical synthesis with focused attention on retrosynthetic
considerations and analysis. The transformations presented are organized
according to bond disconnections and attendant synthetic methods. The review is
expected to lead to better understanding of the characteristics and distinctions
of the two complementary approaches. It depicts for researchers in bio- and
chemocatalysis a road map of challenges and opportunities for the evolution (and
at times revolution) in chemical synthesis.
PMID- 28407392
TI - Comment on Evelmo et al.: Reward responsiveness in patients with chronic pain.
PMID- 28407393
TI - Authors' reply to the comment by Dalton.
PMID- 28407394
TI - Efficacy and safety of onabotulinumtoxinA injection in patients with refractory
overactive bladder: First multicentric study in Turkish population.
AB - AIMS: To investigate the efficacy and safety of intradetrusor onabotulinumtoxinA
(onaBoNT-A) injection in patients with overactive bladder (OAB) refractory to
antimuscarinic treatment. METHODS: A total of 80 patients with OAB symptoms were
enrolled in this prospective multicenter study and received 100 U intradetrusor
onaBoNT-A injection.The changes from baseline in the frequency of voiding, urge
urinary incontinence (UI) and urge episodes, mean and maximum bladder capacities,
uroflowmetry, post-void residual urine volume (PVR), quality of life score, and
treatment benefit scale score were assessed. The need for a second injection,and
treatment-related adverse events were also examined postoperatively. RESULTS:
OnaBoNT-A injection significantly decreased the UI episodes(P = 0.0001), the mean
voiding frequency (P = 0.0001), and the urgency episodes (P = 0.0001) in the
third month compared to baseline. Similarly, the mean bladder capacity, and
maximal bladder capacity were increased (P < 0,05). The quality of life scores
improved by 57.1% compared to the pre-treatment rate (P = 0,0001). No significant
change was observed in the PVR or maximum flow rate. Urinary retention developed
in 3 (3.75%) patients and urinary infection and transient hematuria were observed
in five patients (6.25%) each. The UI episodes, voiding frequency and urgency
episodes were significantly lower at the 9th month than at baseline (all P =
0.0001). Overall 67% of the patients continued to experience benefits from the
injection. Sixteen patients (20%) required a second injection in the third month.
Eight patients were lost to follow-up at the last visit in the 9th month, and 34
of the remaining 56 patients required a second injection at the 9th month.
Cumulatively, 50 (63%) patients needed re-injections. CONCLUSIONS: Our results
demonstrated that the onaBoNT-A injection produced significant improvement in all
OAB symptoms with a low incidence of treatment related adverse events.
PMID- 28407395
TI - Uncovering the Atomistic Mechanism for Calcite Step Growth.
AB - Determining a complete atomic-level picture of how minerals grow from aqueous
solution remains a challenge as macroscopic rates can be a convolution of many
reactions. For the case of calcite (CaCO3 ) in water, computer simulations have
been used to map the complex thermodynamic landscape leading to growth of the two
distinct steps, acute and obtuse, on the basal surface. The carbonate ion is
found to preferentially adsorb at the upper edge of acute steps while Ca2+ only
adsorbs after CO32- . In contrast to the conventional picture, ion pairs prefer
to bind at the upper edge of the step with only one ion, at most, coordinated to
the step and lower terrace. Migration of the first carbonate ion to a growth site
is found to be rate-limiting for kink nucleation, with this process having a
lower activation energy on the obtuse step.
PMID- 28407396
TI - A further family of Stromme syndrome carrying CENPF mutation.
AB - Stromme syndrome is a rare genetic disorder characterized by microcephaly,
anterior ocular chamber anomalies, and "apple peel" type jejunal atresia. Here,
we report a Stromme syndrome family with two affected siblings with a homozygous
truncating frameshift mutation in CENPF. A 3-month-old girl was hospitalized due
to prenatally diagnosed microcephaly, microphthalmia, and dysmorphological
features. The history of a previous child with the same findings in addition to
"apple peel" intestinal atresia had been noted. Regarding the clinical features
of both affected siblings, a diagnosis of Stromme syndrome was established. Exome
sequencing of these two cases showed the homozygous mutation
(c.5912_5913insA)/(p.T1974Nfs*9) in CENPF. While confirmation of this gene being
responsible for Stromme syndrome was pending our results, Filges et al. reported
that CENPF was indeed underlying the reason for Stromme syndrome. This is the
second case report identifying CENPF mutation as the cause of Stromme syndrome.
PMID- 28407397
TI - Whole-protein alanine-scanning mutagenesis of allostery: A large percentage of a
protein can contribute to mechanism.
AB - Many studies of allosteric mechanisms use limited numbers of mutations to test
whether residues play "key" roles. However, if a large percentage of the protein
contributes to allosteric function, mutating any residue would have a high
probability of modifying allostery. Thus, a predicted mechanism that is dependent
on only a few residues could erroneously appear to be supported. We used whole
protein alanine-scanning mutagenesis to determine which amino acid sidechains of
human liver pyruvate kinase (hL-PYK; approved symbol PKLR) contribute to
regulation by fructose-1,6-bisphosphate (Fru-1,6-BP; activator) and alanine
(inhibitor). Each nonalanine/nonglycine residue of hL-PYK was mutated to alanine
to generate 431 mutant proteins. Allosteric functions in active proteins were
quantified by following substrate affinity over a concentration range of
effectors. Results show that different residues contribute to the two allosteric
functions. Only a small fraction of mutated residues perturbed inhibition by
alanine. In contrast, a large percentage of mutated residues influenced
activation by Fru-1,6-BP; inhibition by alanine is not simply the reverse of
activation by Fru-1,6-BP. Moreover, the results show that Fru-1,6-BP activation
would be extremely difficult to elucidate using a limited number of mutations.
Additionally, this large mutational data set will be useful to train and test
computational algorithms aiming to predict allosteric mechanisms.
PMID- 28407398
TI - Influence of bleaching and coloring on ethyl glucuronide content in human hair.
AB - Ethyl glucuronide (EtG) is increasingly used in forensic toxicology as a marker
for alcohol use in analyses of hair samples, especially in abstinence control.
Some cosmetic treatments are considered to markedly reduce the EtG content. In
view of especially many women with coloured hair the present study was performed
to further investigate the effect of a variety of colouring procedures
(bleaching, tinting, permanent and semi-permanent dyeing, henna) on the EtG
content. Untreated hair samples (n = 12, EtG 13.9-64.7 pg/mg) were re-analyzed
(gas chromatography- negative chemical ionization mass spectrometry, 0.8 pg/mg
quantification limit) after different treatment procedures. A decrease of the EtG
content of at least 10% occurred in every case. The reduction in comparison to
the untreated hair was expectedly high for permanent dyeing and bleaching with
18.1% of the initial content (median, range 0.0-50.9%) and 18.4% (0.0-46.7%),
respectively. For henna this was 38.3% (0.0-83.0%), for tinting 70.4% (29.0
90.8%), for semi-permanent dyeing 41.9% (0.0-77.4%). With permanent hair dye the
EtG content was decreased to below 7 pg/mg in 10 of 12 cases, in 3 cases even
below the LOD (0.2 pg/mg). Surprisingly henna treatment without oxidative
component had a marked influence, EtG was below 2 pg/mg in 2 of 12 samples. The
study showed that all tested coloration procedures markedly affected the
deposited EtG content. Even temporary or henna coloration may have a marked
effect. The present data support the recommendation to exclude hair samples with
colour manipulations for analysis on the EtG content as a precaution in alcohol
abstinence programs. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28407400
TI - Designed Spiroketal Protein Modulation.
AB - Spiroketals are structural motifs found in many biologically active natural
products, which has stimulated considerable efforts toward their synthesis and
interest in their use as drug lead compounds. Despite this, the use of
spiroketals, and especially bisbenzanulated spiroketals, in a structure-based
drug discovery setting has not been convincingly demonstrated. Herein, we report
the rational design of a bisbenzannulated spiroketal that potently binds to the
retinoid X receptor (RXR) thereby inducing partial co-activator recruitment. We
solved the crystal structure of the spiroketal-hRXRalpha-TIF2 ternary complex,
and identified a canonical allosteric mechanism as a possible explanation for the
partial agonist behavior of our spiroketal. Our co-crystal structure, the first
of a designed spiroketal-protein complex, suggests that spiroketals can be
designed to selectively target other nuclear receptor subtypes.
PMID- 28407401
TI - Cleaving Direct-Laser-Written Microstructures on Demand.
AB - Using an advanced functional photoresist we introduce direct-laser-written (DLW)
3D microstructures capable of complete degradation on demand. The networks
consist exclusively of reversible bonds, formed by irradiation of a phenacyl
sulfide linker, giving disulfide bonds in a radical-free step-growth
polymerization via a reactive thioaldehyde. The bond formation was verified in
solution by ESI-MS. To induce cleavage, dithiothreitol causes a thiol-disulfide
exchange, erasing the written structure. The mild cleavage of the disulfide
network is highly orthogonal to other, for example, acrylate-based DLW
structures. To emphasize this aspect, DLW structures were prepared incorporating
reversible structural elements into a non-reversible acrylate-based standard
scaffold, confirming subsequent selective cleavage. The high lateral resolution
achievable was verified by the preparation of well-defined line gratings with
line separations of down to 300 nm.
PMID- 28407399
TI - Abnormal Rab11-Rab8-vesicles cluster in enterocytes of patients with microvillus
inclusion disease.
AB - Microvillus inclusion disease (MVID) is a congenital enteropathy characterized by
accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of
enterocytes, historically termed "secretory granules." However, neither their
identity nor pathophysiological significance is well defined. Using
immunoelectron microscopy and tomography, we studied biopsies from MVID patients
(3* Myosin 5b mutations and 1* Syntaxin3 mutation) and compared them to controls
and genome-edited CaCo2 cell models, harboring relevant mutations. Duodenal
biopsies from 2 patients with novel Myosin 5b mutations and typical clinical
symptoms showed unusual ultrastructural phenotypes: aberrant subapical vesicles
and tubules were prominent in the enterocytes, though other histological
hallmarks of MVID were almost absent (ectopic intra-/intercellular microvilli,
brush border atrophy). We identified these enigmatic vesiculo-tubular organelles
as Rab11-Rab8-positive recycling compartments of altered size, shape and location
harboring the apical SNARE Syntaxin3, apical transporters sodium-hydrogen
exchanger 3 (NHE3) and cystic fibrosis transmembrane conductance regulator. Our
data strongly indicate that in MVID disrupted trafficking between cargo vesicles
and the apical plasma membrane is the primary cause of a defect of epithelial
polarity and subsequent facultative loss of brush border integrity, leading to
malabsorption. Furthermore, they support the notion that mislocalization of
transporters, such as NHE3 substantially contributes to the reported sodium loss
diarrhea.
PMID- 28407402
TI - Cirrhotic cardiomyopathy: Implications for liver transplantation.
AB - The majority of patients on a waiting list for liver transplantation have end
stage liver disease. Because of the marked peripheral vasodilatation of end-stage
cirrhosis that masks a latent myocardial dysfunction, cardiac abnormalities in
the resting state are usually subclinical and escape the attention of physicians.
However, when challenged, the systolic and diastolic contractile responses are
attenuated. In addition to these contractile abnormalities, morphological
changes, such as enlargement or hypertrophy of cardiac chambers, and
electrophysiological repolarization changes, including a prolonged QT interval,
can be observed. The constellation of these cardiac abnormalities is termed
cirrhotic cardiomyopathy. Liver transplantation induces significant
cardiovascular stress. Clamping of the inferior vena cava and portal vein,
hemorrhage and blood/volume infusion, and ischemia/reperfusion all cause
hemodynamic fluctuation. The changing cardiac preload and afterload status
increases the cardiac workload, and thus, the previously subclinical ventricular
dysfunction may manifest as overt heart failure during the operative and
perioperative periods. Cardiac dysfunction contributes to morbidity and mortality
associated with liver transplantation. Cardiovascular events are the third
leading cause of death in liver recipients. However, because liver
transplantation is the only definitive treatment for end-stage liver failure and
also appears to reverse cardiac abnormalities, it is important to understand the
challenges of the heart in liver transplantation. This review focuses on cardiac
status before, during, and after liver transplantation. Liver Transplantation 23
826-835 2017 AASLD.
PMID- 28407403
TI - Water-Soluble N-Heterocyclic Carbene-Protected Gold Nanoparticles: Size
Controlled Synthesis, Stability, and Optical Properties.
AB - NHC-AuI complexes were used to prepare stable, water-soluble, NHC-protected gold
nanoparticles. The water-soluble, charged nature of the nanoparticles permitted
analysis by polyacrylamide gel electrophoresis (PAGE), which showed that the
nanoparticles were highly monodisperse, with tunable core diameters between 2.0
and 3.3 nm depending on the synthesis conditions. Temporal, thermal, and chemical
stability of the nanoparticles were determined to be high. Treatment with thiols
caused etching of the particles after 24 h; however larger plasmonic particles
showed greater resistance to thiol treatment. These water-soluble, bio-compatible
nanoparticles are promising candidates for use in photoacoustic imaging, with
even the smallest nanoparticles giving reliable photoacoustic signals.
PMID- 28407404
TI - Reply.
PMID- 28407405
TI - Fibrinogen links podocyte injury with Toll-like receptor 4 and is associated with
disease activity in FSGS patients.
AB - AIM: Fibrinogen (Fg) is reported to participate in inflammation through Toll-like
receptor 4 (TLR4). However, it remains unknown whether Fg might induce podocyte
damage through TLR4 and be related to disease activity in patients with focal
segmental glomerulosclerosis (FSGS). METHODS: We observed Fg-induced alterations
in actin and apoptosis in cultured human podocytes transfected with or without
TLR4 siRNA. Expression of TLR4, phospho-p38 MAPK and phospho-NF-kappaB p65 was
evaluated by quantitative reverse transcription polymerase chain reaction (qRT
PCR) or western blotting, and we analysed urinary Fg levels in adriamycin-treated
mice and double immunofluorescence staining for TLR4, Fg and podocin. Urinary Fg
changes were also analyzed in FSGS patients under prednisone treatment. RESULTS:
First, Fg dose-dependently induced actin damage and apoptosis in cultured human
podocytes, with an Fg-induced increase in TLR4 expression, and TLR4 siRNA
transfection prevented these effects. TLR4 knockdown inhibited activation of p38
MAPK and NF-kappaB p65 in podocytes. Elevated urinary Fg levels were positively
correlated with albuminuria in adriamycin-treated mice, in which Fg and TLR4
colocalized and exhibited increased expression in podocytes. Additionally,
elevated urinary Fg levels were positively correlated with 24-h proteinuria and
foot process width in FSGS patients. Urinary Fg levels were significantly
decreased in patients with complete remission but not in those without remission.
CONCLUSIONS: Fg induced podocytes injury via the TLR4-p38 MAPK-NF-kappaB p65
pathway. In FSGS patients, urinary Fg levels reflect therapeutic response to
prednisone and disease activity.
PMID- 28407406
TI - Phenobarbital in intensive care unit pediatric population: predictive
performances of population pharmacokinetic model.
AB - An external evaluation of phenobarbital population pharmacokinetic model
described by Marsot et al. was performed in pediatric intensive care unit. Model
evaluation is an important issue for dose adjustment. This external evaluation
should allow confirming the proposed dosage adaptation and extending these
recommendations to the entire intensive care pediatric population. External
evaluation of phenobarbital published population pharmacokinetic model of Marsot
et al. was realized in a new retrospective dataset of 35 patients hospitalized in
a pediatric intensive care unit. The published population pharmacokinetic model
was implemented in nonmem 7.3. Predictive performance was assessed by quantifying
bias and inaccuracy of model prediction. Normalized prediction distribution
errors (NPDE) and visual predictive check (VPC) were also evaluated. A total of
35 infants were studied with a mean age of 33.5 weeks (range: 12 days-16 years)
and a mean weight of 12.6 kg (range: 2.7-70.0 kg). The model predicted the
observed phenobarbital concentrations with a reasonable bias and inaccuracy. The
median prediction error was 3.03% (95% CI: -8.52 to 58.12%), and the median
absolute prediction error was 26.20% (95% CI: 13.07-75.59%). No trends in NPDE
and VPC were observed. The model previously proposed by Marsot et al. in neonates
hospitalized in intensive care unit was externally validated for IV infusion
administration. The model-based dosing regimen was extended in all pediatric
intensive care unit to optimize treatment. Due to inter- and intravariability in
pharmacokinetic model, this dosing regimen should be combined with therapeutic
drug monitoring.
PMID- 28407407
TI - Further evidence that a blepharophimosis syndrome phenotype is associated with a
specific class of mutation in the ADNP gene.
AB - Heterozygous truncating mutations in ADNP are associated with a syndromic form of
intellectual disability known as Helsmoortel-van der Aa syndrome. Among 17
previously reported patients with Helsmoortel-van der Aa syndrome, one patient
exhibited blepharophimosis. Whether blepharophimosis represents a phenotypic
expression of the ADNP mutation spectrum or a chance association remains unclear.
Herein, we report another patient with a de novo truncating mutation in ADNP who
exhibited a combination of blepharophimosis and epicanthal folds. In our
retrospective re-evaluation of six originally reported patients whose facial
photographs were available, at least one patient indeed had blepharophimosis and
epicanthal folds. Furthermore, all three patients with blepharophimosis and
epicanthal folds, including the presently reported patient, had truncating
mutations at the same specific portion of the protein, that is the bipartite
nuclear localization signal. We suggest that this specific class of ADNP mutation
is likely associated with a blepharophimosis syndrome phenotype. From a clinical
standpoint, a differential diagnosis of patients with blepharophimosis should
include ADNP mutations in addition to blepharophimosis ptosis epicanthus inversus
syndrome, especially when intellectual disability is present.
PMID- 28407409
TI - Clinical and molecular characterization of a second family with the 12q14
microdeletion syndrome and review of the literature.
AB - The 12q14 microdeletion syndrome is a rare condition characterized by low birth
weight, failure to thrive, short stature, learning disabilities, and
osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the
literature, displaying both phenotypic than genetic variability. We report on
three familial cases, a mother and two brothers, with severe short stature. The
mother and elder brother presented with osteopoikilosis while the younger brother
had severe short stature and developmental delay. SNP array analysis revealed a
1.9 Mb heterozygous 12q14.2q14.3 deletion in all three patients encompassing 14
genes and 3 miRNAs. In addition, the younger brother carried a paternal 11q13.4
duplication including the SHANK2 gene. This latter patient was investigated for
developmental delay and did not show osteopoikilosis, confirming the role of age
in the clinical presentation of this condition. To the best of our knowledge,
this is the second family described with the syndrome. Comparing the clinical and
molecular data of our patients with those previously reported we performed a
detailed genotype-phenotype correlation confirming the association between growth
retardation and osteopoikilosis when the rearrangement includes both LEMD3 and
HMGA2 genes. In addition, we suggest the XPOT, TBK1, WIF1 genes as candidates for
the clinical features observed in our patients and discuss for the first time the
possible involvement of some microRNAs, when deleted, in the etiology of the
phenotypes in 12q14 microdeletion syndrome patients. We expect the interpretation
of our findings to be useful both from a molecular point of view and for genetic
counseling.
PMID- 28407408
TI - FMR1 genotype interacts with parenting stress to shape health and functional
abilities in older age.
AB - This study investigated the association of genotype (CGG repeats in FMR1) and the
health and well-being of 5,628 aging adults (mean age = 71) in a population-based
study. Two groups were contrasted: aging parents who had adult children with
developmental or mental health disabilities (n = 785; the high-stress parenting
group) and aging parents of healthy children who did not have disabilities (n =
4843; the low-stress parenting group). There were significant curvilinear
interaction effects between parenting stress group and CGG repeats for body mass
index and indicators of health and functional limitations, and the results were
suggestive of interactions for limitations in cognitive functioning. Parents who
had adult children with disabilities and whose genotype was two standard
deviations above or below the mean numbers of CGGs had poorer health and
functional outcomes at age 71 than parents with average numbers of CGGs. In
contrast, parents who had healthy adult children and who had similarly high or
low numbers of CGG repeats had better health and functional outcomes than parents
with average numbers of CGGs. This pattern of gene by environment interactions
was consistent with differential susceptibility or the flip-flop phenomenon. This
study illustrates how research that begins with a rare genetic condition (such as
fragile X syndrome) can lead to insights about the general population and
contributes to understanding of how genetic differences shape the way people
respond to environments. (c) 2017 Wiley Periodicals, Inc.
PMID- 28407410
TI - Variable clinical course of identical twin neonates with Alstrom syndrome
presenting coincidentally with dilated cardiomyopathy.
AB - Alstrom Syndrome (AS) is a rare autosomal recessive disorder caused by mutations
in the ALMS1 gene. We report monozygotic twin infants who presented concurrently
with symptoms of congestive heart failure (CHF) due to dilated cardiomyopathy
(DCM). Following their initial presentation, one twin improved both
echocardiographically and functionally while the other twin showed a progressive
decline in ventricular function and worsening CHF symptoms requiring multiple
hospitalizations and augmentation of heart failure therapy. Concordant findings
of nystagmus, vision loss, and developmental delay were noted in both twins.
Additional discordant findings included obesity and signs of insulin resistance
in one twin. Genetic testing on one sibling confirmed AS. These twins underscore
the importance of considering AS in any child presenting with DCM, particularly
in infancy, and highlights that, even in monozygotic twins, the clinical course
of AS is variable with regard to both the cardiac and non-cardiac manifestations
of the disease.
PMID- 28407411
TI - Risk of metachronous colorectal cancer following colectomy in Lynch syndrome: a
systematic review and meta-analysis.
AB - AIM: Lynch syndrome (LS) accounts for 2-4% of all colorectal cancer (CRC) cases,
and is associated with an increased risk of developing metachronous colorectal
cancer (mCRC). The role of extended colectomy in LS CRC is controversial. There
are limited studies comparing the risk of mCRC following segmental colectomy and
extended colectomy. The objective of this systematic review is to evaluate the
risk of developing mCRC following segmental and extended colectomy for LS CRC and
endoscopic compliance. METHOD: A systematic review of major databases was
performed using predefined terms. All original articles published in English
comparing the risk of mCRC in LS patients after segmental and extended colectomy
from 1950 to January 2016 were included. RESULTS: The search retrieved 324
studies. Six studies involving 871 patients met the inclusion criteria. Of these,
705 (80.9%) underwent segmental colectomy and 166 (19.1%) extended colectomy.
Average follow-up was 91.2 months. The mCRC rate was 22.8% and 6% in the
segmental and extended colectomy groups, respectively. The segmental group were
over four times more likely to develop mCRC (OR 4.02, 95% CI: 2.01-8.04, P <
0.0001). mCRC occurred in patients after segmental colectomy despite 1-2-yearly
postoperative endoscopic surveillance. CONCLUSION: This result suggests that
extended colectomy reduces the risk of mCRC by over four-fold compared with
segmental colectomy. mCRC occurred in the segmental group despite postoperative
endoscopic surveillance. This needs to be borne in mind when deciding on the
appropriate surgical management of LS patients with CRC. We recommend that
extended colectomy should be considered for patients with confirmed LS CRC.
PMID- 28407412
TI - Adsorption and Desorption of Single-Stranded DNA from Single-Walled Carbon
Nanotubes.
AB - The chemical affinity of single-stranded DNA (ssDNA) to adsorb to the surface of
single-walled carbon nanotubes (SWCNTs) is used for SWCNT purification,
separation and in bio-devices. Despite the popularity of research on SWCNT-ssDNA
conjugates, very little work has studied the removal of adsorbed ssDNA on SWCNTs.
This paper reports a comprehensive study of biological, physical and chemical
treatments for the removal of ssDNA from SWCNT-ssDNA suspensions. These include
enzymatic cleavage, heat treatment under vacuum up to 400 degrees C, chemical
treatments with high or low pH, oxidizing conditions, and high-ionic-strength
solvents. Complimentary characterization techniques including fluorescence from a
DNA-intercalating dye (YO-PRO-1) and photoelectron spectroscopy are used to
exhaustively study and compare the methods investigated. Enzyme treatment is
found to remove the phosphate backbone only, leaving nucleosides adsorbed to
SWCNTs. Heating in inert atmosphere is ineffective at removing ssDNA. Acid, base
and oxidative treatment are found to be effective for the removal of ssDNA from
SWCNTs. Where possible the mechanism of desorption is described and from the
findings suggestions for "best practices" are provided.
PMID- 28407413
TI - Robotic liver donor right hepatectomy: A pure, minimally invasive approach.
PMID- 28407414
TI - Association of glucagon-like peptide-1 receptor agonist use and rates of acute
myocardial infarction, stroke and overall mortality in patients with type 2
diabetes mellitus in a large integrated health system.
AB - AIMS: To assess the potential impact of glucagon-like peptide-1 receptor agonist
(GLP-1RA) exposure on cardiovascular disease (CVD) and mortality outcomes in
patients with type 2 diabetes (T2D), using a large retrospective cohort. RESEARCH
DESIGN AND METHODS: Patients who had T2D between 2005 and 2014 (N = 105 862) were
identified from the electronic health record system at Cleveland Clinic using a
validated electronic phenotype. A time-dependent, Cox, multiple regression
analysis was used to assess the association between GLP-1RA exposure and risk of
acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and
overall mortality, as well as the composite of all three outcomes. The findings
were further evaluated by assessing the effect of GLP-1RAs on the same variables
in patients with and without prior CVD. The model adjusted for differences in
demographic information, hypertension, laboratory/vital signs, history of
outcomes, and T2D medications. RESULTS: There were significantly lower rates of
AMI (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65 to 0.99; P =
.045), CVA (HR 0.82, 95% CI 0.74 to 0.91, P < .001), overall mortality (HR 0.48,
95% CI 0.41 to 0.57; P < .001), and the composite outcome (HR 0.82, 95% CI 0.74
to 0.91; P < .002) during the consolidated time that patients were exposed to GLP
1RAs compared to corresponding rates during intervals without GLP-1RA exposure.
GLP-1RA treatment was associated with a significant decrease in CVA, mortality,
and the composite outcome in patients with and without established CVD, not
significantly affecting AMI in these subgroups. CONCLUSIONS: GLP-1RA exposure was
found to be associated with a reduction in the risk of cardiovascular events
observed and overall mortality among patients with T2D with and without
established CVD, after adjusting for potential confounders.
PMID- 28407415
TI - Impact of insulin glargine and lixisenatide on beta-cell function in patients
with type 2 diabetes mellitus: A randomized open-label study.
AB - It is known that beta-cell function can be enhanced by direct stimulation of
insulin secretion or by induction of beta-cell rest, but whether both strategies
can complement each other has not yet been examined. A total of 28 people with
type 2 diabetes (glycated haemoglobin 7.8% +/- 0.5%) were treated with either
lixisenatide or titrated insulin glargine, followed by their combined
administration, each over 4 weeks. First- and second-phase insulin secretion
during an intravenous glucose challenge were calculated. First- and second-phase
insulin secretion were not increased with glargine alone, but increased after
addition of lixisenatide ( P < .001). Lixisenatide alone increased first- and
second-phase insulin secretion ( P < .01). Addition of insulin glargine tended
to further increase first-phase insulin secretion (P = .054), as well as insulin
and C-peptide concentrations ( P < .05). Second-phase insulin secretion was not
affected by the addition of glargine. The sequence of initiating lixisenatide or
glargine had no effect on the final measures of glycaemia or insulin secretion.
Thus, lixisenatide and, to a lesser extent, insulin glargine, increase glucose
stimulated insulin secretion in an additive manner.
PMID- 28407417
TI - The Elusive Palladium-Diazo Adduct Captured: Synthesis, Isolation and Structural
Characterization of [(ArNHC-PPh2 )Pd(eta2 -N2 C(Ph)CO2 Et)].
AB - The first example of a diazo palladium adduct is reported. The complexes [(ArNHC
PPh2 )M(eta2 -N2 C(Ph)CO2 Et)] (M=Ni, 3; M=Pd, 4; ArNHC-PPh2 =3-(2,6
diisopropylphenyl)-1-[(diphenylphosphino)ethyl]imidazol-2-ylidene) were prepared
by ligand exchange with styrene-coordinated precursors [(ArNHC-PPh2 )M(styrene)]
(M=Ni, 1; M=Pd, 2). Complex 4 was fully characterized, including X-ray analyses;
this constitutes the first example of a diazo adduct compound with palladium,
thereby closing the gap between Groups 8 and 10 regarding this type of compounds.
PMID- 28407416
TI - Tau-based fluorescent protein fusions to visualize microtubules.
AB - The ability to visualize cytoskeletal proteins and their dynamics in living cells
has been critically important in advancing our understanding of numerous cellular
processes, including actin- and microtubule (MT)-dependent phenomena such as cell
motility, cell division, and mitosis. Here, we describe a novel set of
fluorescent protein (FP) fusions designed specifically to visualize MTs in living
systems using fluorescence microscopy. Each fusion contains a FP module linked in
frame to a modified phospho-deficient version of the MT-binding domain of Tau
(mTMBD). We found that expressed and purified constructs containing a single
mTMBD decorated Xenopus egg extract spindles more homogenously than similar
constructs containing the MT-binding domain of Ensconsin, suggesting that the
binding affinity of mTMBD is minimally affected by localized signaling gradients
generated during mitosis. Furthermore, MT dynamics were not grossly perturbed by
the presence of Tau-based FP fusions. Interestingly, the addition of a second
mTMBD to the opposite terminus of our construct caused dramatic changes to the
spatial localization of probes within spindles. These results support the use of
Tau-based FP fusions as minimally perturbing tools to accurately visualize MTs in
living systems.
PMID- 28407418
TI - Pharmacokinetics and Acid Suppressant Efficacy of Esomeprazole after Intravenous,
Oral, and Subcutaneous Administration to Healthy Beagle Dogs.
AB - BACKGROUND: Esomeprazole is an S-enantiomer of omeprazole that has favorable
pharmacokinetics and efficacious acid suppressant properties in humans. However,
the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have
not been reported. OBJECTIVE: To determine the pharmacokinetics of esomeprazole
administered via various routes (PK study) and to investigate the effect of
esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study).
ANIMALS: Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for
PK and PD study, respectively. METHODS: Both studies used an open, randomized,
and crossover design. In the PK study, 7 dogs received intravenous (IV),
subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment
period was separated by a washout period of at least 10 days. Esomeprazole plasma
concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric
pH was recorded without medication (baseline pH) and following IV, SC, and PO
esomeprazole dosing regimens (1 mg/kg) in 5 dogs. RESULTS: The bioavailability of
esomeprazole administered as PO enteric-coated granules and as SC injections was
71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean +/- SD
percent time intragastric pH was >=3 and >=4 was 58.9 +/- 21.1% and 40.9 +/-
17.3% for IV group, 75.8 +/- 16.4% and 62.7 +/- 17.7% for SC group, 88.2 +/- 8.9%
and 82.5 +/- 7.7% for PO group, and 12.5 +/- 3.6% and 3.7 +/- 1.8% for baseline.
The mean percent time with intragastric pH was >=3 or >=4 was significantly
increased regardless of the dosing route (P < .05). CONCLUSION: The PK parameters
for PO and SC esomeprazole administration were favorable, and esomeprazole
significantly increased intragastric pH after IV, PO, and SC administration. IV
and SC administration of esomeprazole might be useful when PO administration is
not possible. No significant adverse effects were observed.
PMID- 28407419
TI - Antibiotic treatment of biofilm infections.
AB - Bacterial biofilms are associated with a wide range of infections, from those
related to exogenous devices, such as catheters or prosthetic joints, to chronic
tissue infections such as those occurring in the lungs of cystic fibrosis
patients. Biofilms are recalcitrant to antibiotic treatment due to multiple
tolerance mechanisms (phenotypic resistance). This causes persistence of biofilm
infections in spite of antibiotic exposure which predisposes to antibiotic
resistance development (genetic resistance). Understanding the interplay between
phenotypic and genetic resistance mechanisms acting on biofilms, as well as
appreciating the diversity of environmental conditions of biofilm infections
which influence the effect of antibiotics are required in order to optimize the
antibiotic treatment of biofilm infections. Here, we review the current knowledge
on phenotypic and genetic resistance in biofilms and describe the potential
strategies for the antibiotic treatment of biofilm infections. Of note is the
optimization of PK/PD parameters in biofilms, high-dose topical treatments,
combined and sequential/alternate therapies or the use antibiotic adjuvants.
PMID- 28407420
TI - Dental biofilm infections - an update.
AB - Teeth are colonized by oral bacteria from saliva containing more than 700
different bacterial species. If removed regularly, the dental biofilm mainly
comprises oral streptococci and is regarded as resident microflora. But if left
undisturbed, a complex biofilm containing up to 100 bacterial species at a site
will build up and may eventually cause development of disease. Depending on local
ecological factors, the composition of the dental biofilm may vary considerably.
With access to excess carbohydrates, the dental biofilm will be dominated by
mainly gram-positive carbohydrate-fermenting bacteria causing demineralization of
teeth, dental caries, which may further lead to inflammation and necrosis in the
pulp and periapical region, i.e., pulpitis and periapical periodontitis. In supra
and subgingival biofilms, predominantly gram-negative, anaerobic proteolytic
bacteria will colonize and cause gingival inflammation and breakdown of
supporting periodontal fibers and bone and ultimately tooth loss, i.e.,
gingivitis, chronic or aggressive periodontitis, and around dental implants, peri
implantitis. Furthermore, bacteria from the dental biofilm may spread to other
parts of the body by bacteremia and cause systemic disease. Basically, prevention
and treatment of dental biofilm infections are achieved by regular personal and
professional removal of the dental biofilm.
PMID- 28407421
TI - Central venous catheters and biofilms: where do we stand in 2017?
AB - The use of central venous catheters (CVC) is associated with a risk of microbial
colonization and subsequent potentially severe infection. Microbial contamination
of the catheter leads to the development of a microbial consortia associated with
the CVC surface and embedded in an extracellular matrix, named biofilm. This
biofilm provides bacterial cells the ability to survive antimicrobial agents and
the host immune system and to disseminate to other sites of the body. The best
preventive strategy is to avoid any unnecessary catheterization or to reduce
indwelling duration when a CVC is required. Beside aseptic care and antibiotic
impregnated catheters (like minocycline/rifampin), preventive locks can be
proposed in some cases, whereas non-biocidal approaches are under active research
like anti-adhesive or competitive interactions strategies. When the diagnosis of
catheter-related bloodstream infection (CRBSI) is suspected on clinical symptoms,
it requires a microbiological confirmation by paired blood cultures in order to
avoid unnecessary catheter removal. The treatment of CRBSI relies on catheter
removal and systemic antimicrobials. However, antibiotic lock technique (ALT) can
be used as an attempt to eradicate biofilm formed on the inside lumen of the
catheter in case of uncomplicated long-term catheter-related BSI caused by
coagulase-negative staphylococci (CoNS) or Enterobacteriaceae. Recently,
promising strategies have been developed to improve biofilm eradication; they
rely on matrix degradation or destabilization or the development of anti
persister compounds, targeting the most tolerant bacterial cells inside the
biofilm. Understanding biofilm formation at the molecular level may help us to
develop new approaches to prevent or treat these frequent infections.
PMID- 28407422
TI - Microbiological diagnosis of device-related biofilm infections.
AB - Medical device-related infections cause undue patient distress, increased
morbidity and mortality and pose a huge financial burden on healthcare services.
The pathogens are frequently distributed heterogeneously in biofilms, which can
persist without being effectively cleared by host immune defenses and antibiotic
therapy. At present, there is no 'gold standard' available to reveal the presence
of device-related biofilm infections. However, adequate sample collection and
logistics, standardised diagnostic methods, and interpretation of results by
experienced personnel are important steps in efficient diagnosis and treatment of
these infections. The focus of this mini review is on prosthethic joint and
cardiovascular implantable device infections, which exemplify permanent devices
that are placed in a sterile body site. These device-related infections represent
some of the most challenging in terms of both diagnosis and treatment.
PMID- 28407423
TI - Orthopaedic biofilm infections.
AB - Many infections of the musculoskeletal system are biofilm infections that develop
on non-living surfaces. Microorganisms adhere either on dead bone (sequesters) or
implants. As a rule for a curative concept, chronic osteomyelitis or implant
associated bone infection must be treated with a combination of surgery and
antimicrobial therapy. If an implant is kept in place, or a new device is
implanted before complete healing of infection, a biofilm-active antibiotic
should be used. Rifamycins are active against biofilms of staphylococci, and
fluoroquinolones against those of Gram-negative bacilli. In this review, the
management of chronic osteomyelitis, periprosthetic joint infection and implant
associated osteomyelitis of long bones is presented.
PMID- 28407424
TI - Biofilms in orthopedic infections: a review of laboratory methods.
AB - Bacterial infection after hardware implantation in orthopedic surgery is a
devastating issue as it often necessitates increased hospital costs and stays,
multiple revision surgeries, and prolonged use of antibiotics. Because of the
nature of hardware implantation into the body, these infections are commonly in
the form of attached biofilms. The current literature on a range of methodologies
to study clinically explanted infected orthopedic hardware, with potential
biofilm, in the laboratory setting is limited. General methods include
traditional and advanced culturing techniques, microscopy imaging techniques, and
techniques that manipulate genetic material. The future of diagnostic techniques
for infected implants, innovative hardware design, and treatment solutions for
patients all depend on the successful evaluation and characterization of clinical
samples in the laboratory setting. This review provides an overview of current
methods to study biofilms associated with orthopedic infections and insight into
future directions in the field.
PMID- 28407425
TI - Antifouling and antimicrobial biomaterials: an overview.
AB - The use of implantable medical devices is a common and indispensable part of
medical care for both diagnostic and therapeutic purposes. However, as side
effect, the implant of medical devices quite often leads to the occurrence of
difficult-to-treat infections, as a consequence of the colonization of their
abiotic surfaces by biofilm-growing microorganisms increasingly resistant to
antimicrobial therapies. A promising strategy to combat device-related infections
is based on anti-infective biomaterials that either repel microbes, so they
cannot attach to the device surfaces, or kill them in the surrounding areas. In
general, such biomaterials are characterized by antifouling coatings, exhibiting
low adhesion or even repellent properties towards microorganisms, or
antimicrobial coatings, able to kill microbes approaching the surface. In this
light, the present overview will address the development in the last two decades
of antifouling and antimicrobial biomaterials designed to potentially limit the
initial stages of microbial adhesion, as well as the microbial growth and biofilm
formation on medical device surfaces.
PMID- 28407426
TI - A short history of microbial biofilms and biofilm infections.
AB - The observation of aggregated microbes surrounded by a self-produced matrix
adhering to surfaces or located in tissues or secretions is old since both
Leeuwenhoek and Pasteur have described the phenomenon. In environmental and
technical microbiology, biofilms, 80-90 years ago, were already shown to be
important for biofouling on submerged surfaces, for example, ships. The concept
of biofilm infections and their importance in medicine was, however, initiated in
the early 1970s by the observation of heaps of Pseudomonas aeruginosa cells in
sputum and lung tissue from chronically infected cystic fibrosis patients. The
term biofilm was introduced into medicine in 1985 by J. W. Costerton. During the
following decades, the number of published biofilm articles and methods for
studying biofilms increased rapidly and it was shown that adhering and
nonadhering biofilm infections are widespread in medicine. The medical importance
of biofilm infections is now generally accepted and guidelines for prophylaxis,
diagnosis, and treatment have been published.
PMID- 28407427
TI - Microenvironmental characteristics and physiology of biofilms in chronic
infections of CF patients are strongly affected by the host immune response.
AB - In vitro studies of Pseudomonas aeruginosa and other pathogenic bacteria in
biofilm aggregates have yielded detailed insight into their potential growth
modes and metabolic flexibility under exposure to gradients of substrate and
electron acceptor. However, the growth pattern of P. aeruginosa in chronic lung
infections of cystic fibrosis (CF) patients is very different from what is
observed in vitro, for example, in biofilms grown in flow chambers. Dense in
vitro biofilms of P. aeruginosa exhibit rapid O2 depletion within <50-100 MUm due
to their own aerobic metabolism. In contrast, in vivo investigations show that P.
aeruginosa persists in the chronically infected CF lung as relatively small cell
aggregates that are surrounded by numerous PMNs, where the activity of PMNs is
the major cause of O2 depletion rendering the P. aeruginosa aggregates anoxic.
High levels of nitrate and nitrite enable P. aeruginosa to persist fueled by
denitrification in the PMN-surrounded biofilm aggregates. This configuration
creates a potentially long-term stable ecological niche for P. aeruginosa in the
CF lung, which is largely governed by slow growth and anaerobic metabolism and
enables persistence and resilience of this pathogen even under the recurring
aggressive antimicrobial treatments of CF patients. As similar slow growth of
other CF pathogens has recently been observed in endobronchial secretions, there
is now a clear need for better in vitro models that simulate such in vivo growth
patterns and anoxic microenvironments in order to help unravel the efficiency of
existing or new antimicrobials targeting anaerobic metabolism in P. aeruginosa
and other CF pathogens. We also advocate that host immune responses such as PMN
driven O2 depletion play a central role in the formation of anoxic microniches
governing bacterial persistence in other chronic infections such as chronic
wounds.
PMID- 28407428
TI - Editorial.
PMID- 28407429
TI - Biofilms and host response - helpful or harmful.
AB - Biofilm infections are one of the modern medical world's greatest challenges.
Probably, all non-obligate intracellular bacteria and fungi can establish
biofilms. In addition, there are numerous biofilm-related infections, both
foreign body-related and non-foreign body-related. Although biofilm infections
can present in numerous ways, one common feature is involvement of the host
response with significant impact on the course. A special characteristic is the
synergy of the innate and the acquired immune responses for the induced
pathology. Here, we review the impact of the host response for the course of
biofilm infections, with special focus on cystic fibrosis, chronic wounds and
infective endocarditis.
PMID- 28407430
TI - Chronic urinary tract infections in patients with spinal cord lesions - biofilm
infection with need for long-term antibiotic treatment.
AB - Patients suffering from spinal cord injuries resulting in complete or incomplete
paraplegia or tetraplegia are highly disposed to frequent, recurrent or even
chronic urinary tract infections (UTIs). The reason for the increased risk of
acquiring UTIs is multifactorial, including reduced sensation of classical UTI
symptoms, incomplete bladder emptying, frequent catheterizations or chronic
urinary tract catheters. Biofilms in relation to UTIs have been shown both on
catheters, on concrements or as intracellular bacterial communities (IBCs). Due
to the increased risk of acquiring recurrent or chronic UTIs and frequent
antibiotic treatments, patients experience an increased risk of being infected
with antibiotic-resistant bacteria like extended-spectrum beta-lactamase
producing Escherichia coli or Klebsiella spp., but also bacteria like Pseudomonas
aeruginosa inherently resistant to several antibiotics. Diagnosing the UTI can
also be challenging, especially distinguishing harmless colonization from
pathogenic infection. Based on a previous study showing activation of humoral
immune response toward UTI pathogens in patients with spinal cord lesions (SCL),
the present mini review is an evaluation of using antibody response as an
indicator of chronic biofilm UTI. In addition, we evaluated the effect of long
term treatment with antibiotics in patients with SCLs and chronic UTI, defined by
culturing of a uropathogen in the urine and elevated specific precipitating
antibodies against the same uropathogen in a blood sample. Elimination of chronic
UTI, decrease in specific precipitating antibody values and avoiding selection of
new multidrug-resistant (MDR) uropathogens were the primary markers for effect of
treatment. The results of this evaluation suggest that the long-term treatment
strategy in SCL patients with chronic UTI may be effective; however, randomized
prospective results are needed to confirm this.
PMID- 28407431
TI - In vitro studies evaluating the effects of biofilms on wound-healing cells: a
review.
AB - Chronic wounds are characterized as wounds that have failed to proceed through
the well-orchestrated healing process and have remained open for months to years.
Open wounds are at risk for colonization by opportunistic pathogens. Bacteria
that colonize the open wound bed form surface-attached, multicellular communities
called biofilms, and chronic wound biofilms can contain a diverse microbiota.
Investigators are just beginning to elucidate the role of biofilms in chronic
wound pathogenesis, and have simplified the complex wound environment using in
vitro models to obtain a fundamental understanding of the impact of biofilms on
wound-healing cell types. The intent of this review is to describe current in
vitro methodologies and their results. Investigations started with one host cell
type and single species biofilms and demonstrated that biofilms, or their
secretions, had deleterious effects on wound-healing cells. More complex systems
involved the use of multiple host cell/tissue types and single species biofilms.
Using human skin-equivalent tissues, investigators demonstrated that a number of
different species can grow on the tissue and elicit an inflammatory response from
the tissue. A full understanding of how biofilms impact wound-healing cells and
host tissues will have a profound effect on how chronic wounds are treated.
PMID- 28407432
TI - Diagnosis of biofilm infections in cystic fibrosis patients.
AB - Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients
is the best described biofilm infection in medicine. The initial focus can be the
paranasal sinuses and then follows repeated colonization and infection of the
lungs by aspiration. The matrix of the biofilms is dominated by alginate and the
pathogenesis of tissue damage is immune complex-mediated chronic inflammation
dominated by polymorphonuclear leukocytes and their products (DNA, oxygen
radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by
microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where
aggregates of the bacteria are found surrounded by the abundant alginate matrix.
Specific PNA-FISH probes can be used to identify P. aeruginosa and other
pathogens in situ in the biofilms. Growth of mucoid colonies from the locations
mentioned above is also diagnostic for biofilm infection. Rise of specific anti
P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung
infection, sIgA in saliva or nasal secretions in case of paranasal sinus
infection. Similar approaches have been developed to diagnose chronic biofilm
infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas,
Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus
complex.
PMID- 28407433
TI - Spatiotemporal Evolution of the Wound Repairing Process in a 3D Human Dermis
Equivalent.
AB - Several skin equivalent models have been developed to investigate in vitro the re
epithelialization process occurring during wound healing. Although these models
recapitulate closure dynamics of epithelial cells, they fail to capture how a
wounded connective tissue rebuilds its 3D architecture until the evolution in a
scar. Here, the in vitro tissue repair dynamics of a connective tissue is
replicated by using a 3D human dermis equivalent (3D-HDE) model composed of
fibroblasts embedded in their own extracellular matrix (ECM). After inducing a
physical damage, 3D-HDE undergoes a series of cellular and extracellular events
quite similar to those occurring in the native dermis. In particular, fibroblasts
differentiation toward myofibroblasts phenotype and neosynthesis of hyaluronic
acid, fibronectin, and collagen during the repair process are assessed. Moreover,
tissue reorganization after physical damage is investigated by measuring the
diameter of bundles and the orientation of fibers of the newly formed ECM
network. Finally, the ultimate formation of a scar-like tissue as physiological
consequence of the repair and closure process is demonstrated. Taking together,
the results highlight that the presence of cell-assembled and responsive stromal
components enables quantitative and qualitative in vitro evaluation of the
processes involved in scarring during wound healing.
PMID- 28407434
TI - Spatiotemporal characterization of hydration process of asymmetric polymeric
wound dressings for decubitus ulcers.
AB - Pressure ulcers belong to the most chalenging clinical problems. As hydration
level of such wounds is important for optimal healing, preparation of new wound
dressing (WD) materials for pressure ulcers requires thorough in vitro evaluation
as prerequisite to final in vivo testing. The aims of the study were to: (a)
develop a simple method of preparation of asymmetric polymeric membrane, (b) to
propose a set of in vitro methods for membrane characterization during hydration.
A polyvinyl alcohol asymmetric membrane with homogeneous skin layer and porous
spongy layer was developed with nonadhesive properties and ability to absorb and
retain the water. Complementary methods, including magnetic resonance imaging,
allowed quantitative assessment of spatiotemporal aspects of membrane hydration,
that is, global water uptake; swelling; local hydration in terms of proton
density mapping; spatial distribution of T2 relaxation time; Young's modulus;
piercing resistance. The proposed method of initial wound dressing evaluation
seems to be promising to compare various WD formulations, to assess the time
required to prepare WD membrane to be applied to the wound and to assess how long
WD retains desired working properties. The developed asymmetric membrane seems to
be a good candidate for further evaluation. It was found that: Young's modulus of
hydrated membrane was comparable to those of human skin; asymmetrical structure
was retained during the entire hydration period; each layer had its own distinct,
hydration related, properties and their spatiotemporal evolution; relatively slow
changes of membrane properties during the potential WD application time-span of
several hours was observed. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res
Part B: Appl Biomater, 106B: 843-853, 2018.
PMID- 28407435
TI - SL15: A seminal plasma-derived lectin from the sperm of llama (Lama glama).
AB - The oviductal sperm reservoir of South American camelids is formed when sperm
bind to N-acetylgalactosamine (GalNAc) on the surface of oviductal epithelium.
The aim of this study was to characterize the GalNAc-binding proteins on llama
sperm, and to establish their origin. Sperm-adsorbed proteins were extracted with
0.5 M KCl in Hepes-balanced salts. Sperm-adsorbed and seminal plasma proteins
were then subjected to ligand blotting for their GalNAc affinity, and the labeled
bands were identified by mass spectrometry. Three proteins were identified in
seminal plasma versus only one in the sperm-adsorbed population; SL15, a seminal
lectin, was common to both. SL15 is a homologue of Zymogen granule protein 16,
homolog B-like, which belongs to the Jacalin-related lectin family. This lectin
is likely presented to sperm via seminal plasma since epididymal sperm are not
capable of binding GalNAc, whereas ejaculated sperm does, and its transcript was
enriched predominantly in the prostate and bulbourethral glands. This is the
first report of a seminal lectin in South American camelids that originates in
the male reproductive tract, and is probably involved in sperm reservoir
formation.
PMID- 28407436
TI - Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is
associated with virological suppression in HIV-infected adults in Dakar, Senegal.
AB - OBJECTIVE: To determine the prevalence and factors associated with optimal
antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV
infected adults enrolled in the national ART programme at the teaching hospital
of Fann, Dakar, Senegal. METHODS: Cross-sectional study from 1 September 2013 to
30 January 2014. OUTCOMES: (1) optimal ART adherence by the Center for Adherence
Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000
copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity
(Se), specificity (Sp), positive predictive value (PPV), negative predictive
value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate
logistic regression analysis was performed to identify independent factors
associated with optimal adherence and VLF. RESULTS: Of 98 HIV-infected patients
on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57
of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based
first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART
adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were
significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P =
0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4
93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV
(76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml.
Factors independently associated with VLF were CASE Index Score <10 ([aOR] =
13.0, 95% CI: 1.1-147.9; P = 0.04) and being a boosted PI-based ART regimen
([aOR] = 27.0, 95% CI: 2.4-309.4; P = 0.008). CONCLUSIONS: Optimal ART adherence
is achievable in a high proportion of HIV-infected adults in this study
population. CASE Index Score was independently associated with virological
outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in
this setting.
PMID- 28407437
TI - Hit pause: Developmental arrest in annual killifishes and their close relatives.
AB - Killifishes survive and persist in extreme environments by exploiting both
aquatic and terrestrial habitats for egg deposition, and by adjusting the length
of development to match availability of water to support larval growth and
maturation. Annual killifishes persist in ephemeral bodies of water through the
production of drought-tolerant embryos. Survival of the environmental stresses
associated with their highly variable and seasonal habitat is supported by their
ability to enter into at least two states of metabolic and developmental
dormancy, diapause or quiescence. There are three stages of diapause in annual
killifishes, one occurring prior to gastrulation, one about midway through
development, and one in late pre-hatching embryos. Quiescence may occur at any
developmental stage. In addition, delayed hatching is known to occur in close
relatives of the annual killifishes, and may be superficially confused with pre
hatching diapause. These types of developmental delay are induced by different
cues and serve different purposes in the life history of the species. Thus, it is
likely that the molecular mechanisms that induce dormancy and support survival
are unique in each case. It is imperative that we properly define these forms of
developmental dormancy in our studies in order to put our results into the proper
ecological and evolutionary context. Here the unique characteristics of these
distinct categories of developmental delay are reviewed. Developmental Dynamics
246:858-866, 2017. (c) 2017 The Authors Developmental Dynamics published by Wiley
Periodicals, Inc. on behalf of American Association of Anatomists.
PMID- 28407438
TI - Process Intensification for Cellulosic Biorefineries.
AB - Utilization of renewable carbon source, especially non-food biomass is critical
to address the climate change and future energy challenge. Current chemical and
enzymatic processes for producing cellulosic sugars are multistep, and energy-
and water-intensive. Techno-economic analysis (TEA) suggests that upstream
lignocellulose processing is a major hurdle to the economic viability of the
cellulosic biorefineries. Process intensification, which integrates processes and
uses less water and energy, has the potential to overcome the aforementioned
challenges. Here, we demonstrate a one-pot depolymerization and saccharification
process of woody biomass, energy crops, and agricultural residues to produce
soluble sugars with high yields. Lignin is separated as a solid for selective
upgrading. Further integration of our upstream process with a reactive extraction
step makes energy-efficient separation of sugars in the form of furans. TEA
reveals that the process efficiency and integration enable, for the first time,
economic production of feed streams that could profoundly improve process
economics for downstream cellulosic bioproducts.
PMID- 28407439
TI - Flexible Li-CO2 Batteries with Liquid-Free Electrolyte.
AB - Developing flexible Li-CO2 batteries is a promising approach to reuse CO2 and
simultaneously supply energy to wearable electronics. However, all reported Li
CO2 batteries use liquid electrolyte and lack robust electrolyte/electrodes
structure, not providing the safety and flexibility required. Herein we
demonstrate flexible liquid-free Li-CO2 batteries based on
poly(methacrylate)/poly(ethylene glycol)-LiClO4 -3 wt %SiO2 composite polymer
electrolyte (CPE) and multiwall carbon nanotubes (CNTs) cathodes. The CPE
(7.14*10-2 mS cm-1 ) incorporates with porous CNTs cathodes, displaying stable
structure and small interface resistance. The batteries run for 100 cycles with
controlled capacity of 1000 mAh g-1 . Moreover, pouch-type flexible batteries
exhibit large reversible capacity of 993.3 mAh, high energy density of 521 Wh kg
1 , and long operation time of 220 h at different degrees of bending (0-360
degrees ) at 55 degrees C.
PMID- 28407440
TI - Improving education and supervision of Queensland X-ray Operators through video
conference technology: A teleradiography pilot project.
AB - INTRODUCTION: X-ray Operator (XO) supervision in Queensland is performed by
radiographers in a site removed from the XO site. This has historically been
performed by telephone when the XO requires immediate help, as well as post
examination through radiographer review and the provision of written feedback on
images produced. This project aimed to improve image quality through the
provision of real-time support of XOs by the introduction of video conference
(VC) supervision. METHODS: A 6-month pilot project compared image quality with
and without VC supervision. VC equipment was installed in the X-ray room at two
rural sites, as well as at the radiographer site, to enable visual and oral
supervision. The VC unit enabled visualisation of the X-ray examination technique
as it was being undertaken, as well as the images produced prior to transmission
to the Picture Archiving and Communication System (PACS). RESULTS: Statistically
significant improvement in image quality criteria measures were seen for patient
positioning (P = 0.008), image quality (P < 0.001) and diagnostic value (P <
0.001) of images taken during this project. No statistically significant
differences were seen during case level assessment in the inclusion of only
appropriate imaging (P = 0.06), and the inclusion of unacceptable imaging (P =
0.06), however improvements were seen in both of these criteria. The survey
revealed 24.6% of examinations performed would normally have involved the XO
contacting the radiographer for assistance, although, assistance was actually
provided in 88.3% of examinations. CONCLUSION: This project has demonstrated that
significant improvement in image quality is achievable with VC supervision. A
larger study with a control arm that did not receive direct supervision should be
used to validate the findings of this study.
PMID- 28407441
TI - Same policy, different impact: Center-level effects of share 35 liver allocation.
AB - Early studies of national data suggest that the Share 35 allocation policy
increased liver transplants without compromising posttransplant outcomes. Changes
in center-specific volumes and practice patterns in response to the national
policy change are not well characterized. Understanding center-level responses to
Share 35 is crucial for optimizing the policy and constructing effective future
policy revisions. Data from the United Network for Organ Sharing were analyzed to
compare center-level volumes of allocation-Model for End-Stage Liver Disease
(aMELD) >= 35 transplants before and after policy implementation. There was
significant center-level variation in the number and proportion of aMELD >= 35
transplants performed from the pre- to post-Share 35 period; 8 centers accounted
for 33.7% of the total national increase in aMELD >= 35 transplants performed in
the 2.5-year post-Share 35 period, whereas 25 centers accounted for 65.0% of the
national increase. This trend correlated with increased listing at these centers
of patients with Model for End-Stage Liver Disease (MELD) >= 35 at the time of
initial listing. These centers did not overrepresent the total national volume of
liver transplants. Comparison of post-Share 35 aMELD to calculated time-of
transplant (TOT) laboratory MELD scores showed that only 69.6% of patients
transplanted with aMELD >= 35 maintained a calculated laboratory MELD >= 35 at
the TOT. In conclusion, Share 35 increased transplantation of aMELD >= 35
recipients on a national level, but the policy asymmetrically impacted practice
patterns and volumes of a subset of centers. Longer-term data are necessary to
assess outcomes at centers with markedly increased volumes of high-MELD
transplants after Share 35. Liver Transplantation 23 741-750 2017 AASLD.
PMID- 28407443
TI - The effect of training on noise reduction in neonatal intensive care units.
AB - PURPOSE: Noise, an environmental stimulus, is especially important in the
neurobehavioral development of newborns and brain development of infants at high
risk. Conditions in the neonatal intensive care units (NICUs) may cause certain
sensory stimuli that are not appropriate for the development of newborns,
especially preterm infants. This study was conducted in order to determine noise
levels in the NICU and to evaluate the effect of training provided for noise
control. DESIGN AND METHODS: This study was conducted as a pretest-posttest
quasiexperimental design between September and November 2014 in a 30-bed NICU of
a tertiary hospital in Istanbul. A sample group consisting of 30 people (26
nurses, 4 care workers). Noise measurement devices were used in the Training
Program of Noise Control. RESULTS: Of the health professionals, 96.7% were women,
86.7% were nurses, and 63.3% were university graduates. Some 36.7% of the health
professionals had worked within the unit for more than 5 years. Noise
measurements of full implementations were made over three 24-h periods. Noise
measurements were taken before and after the training on Monday, Friday, and
Sunday. Noise levels after training diminished in all three measurements, and the
decrease was found statistically significant (P < 0.01). PRACTICE IMPLICATIONS:
Planned Noise Control Training for health professionals who work in NICUs is an
effective way of reducing noise. We recommend that this training should be given
to NICU health professionals and noise levels should be determined through
measurements at specific times.
PMID- 28407442
TI - Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants
when co-delivered with norovirus VLPs.
AB - A subunit protein vaccine candidate based on norovirus (NoV) virus-like particles
(VLPs) and rotavirus (RV) VP6 protein against acute childhood gastroenteritis has
been proposed recently. RV VP6 forms different oligomeric nanostructures,
including tubes and spheres when expressed in vitro, which are highly immunogenic
in different animal models. We have shown recently that recombinant VP6 nanotubes
have an adjuvant effect on immunogenicity of NoV VLPs in mice. In this study, we
investigated if the adjuvant effect is dependent upon a VP6 dose or different VP6
structural assemblies. In addition, local and systemic adjuvant effects as well
as requirements for antigen co-delivery and co-localization were studied. The
magnitude and functionality of NoV GII.4-specific antibodies and T cell responses
were tested in mice immunized with GII.4 VLPs alone or different combinations of
VLPs and VP6. A VP6 dose-dependent adjuvant effect on GII.4-specific antibody
responses was observed. The adjuvant effect was found to be strictly dependent
upon co-administration of NoV GII.4 VLPs and VP6 at the same anatomic site and at
the same time. However, the adjuvant effect was not dependent on the types of
oligomers used, as both nanotubes and nanospheres exerted adjuvant effect on
GII.4-specific antibody generation and, for the first time, T cell immunity.
These findings elucidate the mechanisms of VP6 adjuvant effect in vivo and
support its use as an adjuvant in a combination NoV and RV vaccine.
PMID- 28407444
TI - Familial 18q12.2 deletion supports the role of RNA-binding protein CELF4 in
autism spectrum disorders.
AB - Deletion of 18q12.2 is an increasingly recognized condition with a distinct
neuropsychiatric phenotype. Twenty-two patients have been described with
overlapping neurobehavioral disturbances including developmental delay,
intellectual disability of variable degree, seizures, motor coordination
disorder, behavioral/emotional disturbances, and autism spectrum disorders. The
CUGBP Elav-like family member 4 (CELF4) gene at 18q12.2 encodes a RNA-binding
protein that links to RNA subsets involved in pre- and postsynaptic
neurotransmission including almost 30% of potential autism-related genes.
Haploinsufficiency of CELF4 was associated with an autism or autistic behavior
diagnosis in two adult patients with de novo 18q12.2 deletions. We report on a
girl and her mildly affected mother with a 275 kb deletion at 18q12.2 involving
CELF4 and KIAA1328 whose disruption is not associated with any known disease. The
child was diagnosed with syndromic intellectual disability and autism at 6 years
of age. Her mother had minor dysmorphisms, mild intellectual disability, and
autistic behavior. The deleted region reported in this family is one of the
smallest so far reported at 18q12.2. This is also the first full clinical
description of maternally inherited CELF4 haploinsufficiency. The present study
refines the molecular and neuropsychiatric phenotype associated with 18q12.2
deletion leading to CELF4 haploinsufficiency and provides evidence for a role for
CELF4 in brain development and autism spectrum disorders.
PMID- 28407445
TI - Lethal Bentazone Intoxication - A Report of Two Cases.
AB - This study presents two cases of lethal bentazone poisonings, their clinical
presentation, the course of the disease and the autopsy findings. The first is a
50-year-old male who had sprayed corn with a solution of bentazone and was
admitted to the hospital with sweating, fever, nausea, vomiting of aqueous and
hemorrhagic content, and bloody, watery stools. He was treated according to the
symptoms including extracorporeal hemodialysis, but eventually suffered from
multiorgan failure (acute respiratory failure, acute liver failure, coagulopathy,
acute renal failure, metabolic acidosis, and gastrointestinal bleeding) and died
11.35 h after admittance. The cause of death was probable bentazone intoxication.
The second case, also a male, aged 49 who committed suicide by ingesting a
bentazone solution. He was transferred to the hospital prostrated and cyanotic
and died 14.15 h after admittance despite all efforts by the hospital staff. The
cause of death was acute bentazone intoxication.
PMID- 28407447
TI - Hierarchical Micro/Nanofibrous Bioscaffolds for Structural Tissue Regeneration.
AB - Various biomimetic scaffolds with hierarchical micro/nanostructures are designed
to closely mimic native extracellular matrix network and to guide cell behavior
to promote structural tissue generation. However, it remains a challenge to
fabricate hierarchical micro/nanoscaled fibrous scaffolds with different
functional components that endow the scaffolds with both biochemical and physical
features to exert different biological roles during the process of tissue
healing. In this study, a biomimetic designed micro/nanoscaled scaffold with
integrated hierarchical dual fibrillar components is fabricated in order to
repair dura mater and prevent the formation of epidural scars via collagen
molecule self-assembly, electrospinning, and biological interface crosslinking
strategies. The fabricated biomimetic scaffolds display micro/nanofibers
staggered hierarchical architecture with good mechanical properties and
biocompatibility, and it has a more profound effect on attachment, proliferation,
and differentiation of fibroblasts. Using a rabbit duraplasty model in vivo, the
authors find that dural defects repaired with hierarchical micro/nanoscaled
scaffold form a continuous neodura tissue similar to native dura mater;
furthermore, the number of scar tissues decreases significantly in the
laminectomy sites compared with conventional electrospun microfibrous scaffold.
Taken together, these data suggest that the hierarchical micro/nanoscaled fibrous
scaffolds with dual fibrillar components may act as a "true" dural substitutes
for dual repair.
PMID- 28407446
TI - Doping control study of AICAR in post-race urine and plasma samples from horses.
AB - Acadesine, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, commonly known
as AICAR, is a naturally occurring adenosine monophosphate-activated protein
kinase (AMPK) activator in many mammals, including humans and horses. AICAR has
attracted considerable attention recently in the field of doping control because
of a study showing the enhancement of endurance performance in unexercised or
untrained mice, resulting in the term 'exercise pill'. Its use has been
classified as gene doping by the World Anti-Doping Agency (WADA), and since it is
endogenous, it may only be possible to control deliberate administration of AICAR
to racehorses after establishment of an appropriate threshold. Herein we report
our studies of AICAR in post-race equine urine and plasma samples including
statistical studies of AICAR concentrations determined from 1,470 urine samples
collected from thoroughbreds and standardbreds and analyzed in Australia, France,
and Hong Kong. Quantification methods in equine urine and plasma using liquid
chromatography-mass spectrometry were developed by the laboratories in each
country. An exchange of spiked urine and plasma samples between the three
countries was conducted, confirming no significant differences in the methods.
However, the concentration of AICAR in plasma was found to increase upon
haemolysis of whole blood samples, impeding the establishment of a suitable
threshold in equine plasma. A possible urine screening cut-off at 600 ng/mL for
the control of AICAR in racehorses could be considered for adoption. Application
of the proposed screening cut-off to urine samples collected after intravenous
administration of a small dose (2 g) of AICAR to a mare yielded a short detection
time of approximately 4.5 h. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28407448
TI - Draft genomes of the corallimorpharians Amplexidiscus fenestrafer and Discosoma
sp.
AB - Corallimorpharia are the closest noncalcifying relatives of reef-building corals.
Aside from their popularity among aquarium hobbyists, their evolutionary position
between the Actiniaria (sea anemones) and the Scleractinia (hard corals) makes
them ideal candidates for comparative studies aiming at understanding the
evolution of hexacorallian orders in general and reef-building corals in
particular. Here we have sequenced and assembled two draft genomes for the
Corallimorpharia species Amplexidiscus fenestrafer and Discosoma sp. The draft
genomes encompass 370 and 445 Mbp, respectively, and encode for 21,372 and 23,199
genes. To facilitate future studies using these resources, we provide annotations
for the predicted gene models-not only at gene level, by annotating gene models
with the function of the best-matching homologue, and GO terms when available;
but also at protein domain level, where gene function can be better verified
through the conservation of the sequence and order of protein domains. Further,
we provide an online platform (http://corallimorpharia.reefgenomics.org), which
includes a blast interface and a genome browser to facilitate the use of these
resources. We believe that these two genomes are important resources for future
studies on hexacorallian systematics and the evolutionary basis of their specific
traits such as the symbiotic relationship with dinoflagellates of the genus
Symbiodinium or the evolution of calcification in reef-building corals.
PMID- 28407449
TI - Drug interactions and safety profiles with concomitant use of caspofungin and
calcineurin inhibitors in allogeneic haematopoietic cell transplantation.
AB - AIM: Small-scale clinical studies have reported on drug interactions between
caspofungin (CPFG) and calcineurin inhibitors in healthy subjects; however,
little is known about these interactions in allogeneic haematopoietic cell
transplantation (allo-HCT) patients. METHODS: We retrospectively assessed the
drug interactions and safety profiles in allo-HCT recipients treated
concomitantly with CPFG and calcineurin inhibitors. RESULTS: Ninety-one
consecutive cases were evaluated. There were no statistically significant
differences in the plasma concentration/dose (C/D) ratios of tacrolimus (TAC) in
34 patients before and after co-administration with CPFG (median: 575.6-672.4, P
= 0.200). In contrast, the median C/D ratio of cyclosporin A (CsA) in 16 patients
was significantly elevated after co-administration with CPFG (median: 62.8-74.9,
P = 0.016). There were no serious adverse effects on liver or renal function
associated with the therapy. CONCLUSIONS: Our data show that CPFG did not affect
the pharmacokinetics of TAC and that it could mildly increase CsA blood
concentrations in allo-HCT patients.
PMID- 28407450
TI - Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid
anaphylactoid reactions.
AB - Vitamin K1 injection induces severe dose-related anaphylactoid reactions and
overdose for the treatment of vitamin K deficiency. We aimed to find an optimal
and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid
anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient
diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were
performed in beagle dogs to observe anaphylactoid reactions. The results showed
an increased protein induced by vitamin K absence or antagonist II (PIVKA-II)
levels, a prolonging of prothrombin time (PT) and activated partial
thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation
factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01
mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin
K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and
FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1
groups, coagulation functions completely returned to normal. Moreover, the amount
of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal.
Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount.
There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg,
which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated
that a small dose of vitamin K1 is effective to improve vitamin K deficiency and
to prevent anaphylactoid reactions, simultaneously.
PMID- 28407451
TI - Heterotetracenes: Flexible Synthesis and in Silico Assessment of the Hole
Transport Properties.
AB - Thienoacenes and furoacenes are among the most frequent molecular units found in
organic materials. The efficient synthesis of morphologically different
heteroacenes and the rapid determination of their solid-state and electronic
properties are still challenging tasks, which slow down progress in the
development of new materials. Here, we report a flexible and efficient synthesis
of unprecedented heterotetracenes based on a platinum- and gold-catalyzed
cyclization-alkynylation domino process using EthynylBenziodoXole (EBX)
hypervalent iodine reagents in the key step. The proof-of-principle in silico
estimation of the synthesized tetracenes' charge transport properties reveals
their strong dependence on both the position and nature of the heteroatoms in the
ring system. A broad range of mobility is predicted, with some compounds
displaying performance potentially comparable to that of state-of-the-art
electronic organic materials.
PMID- 28407452
TI - Uptake and performance of prevention of mother-to-child transmission and early
infant diagnosis in pregnant HIV-infected women and their exposed infants at
seven health centres in Addis Ababa, Ethiopia.
AB - OBJECTIVE: To assess the uptake of WHO-recommended PMTCT procedures in Ethiopia's
health services. METHODS: Prospective observational study of HIV-positive
pregnant mothers and their newborns attending PMTCT services at seven health
centres in Addis Ababa. Women were recruited during antenatal care and followed
up with their newborns at delivery, Day 6 and Week 6 post-partum. Retention to
PMCTC procedures, self-reported antiretroviral treatment (ART) adherence and HIV
infant outcome were assessed. Turnaround times of HIV early infant diagnosis
(EID) procedures were extracted from health registers. RESULTS: Of 494 women
enrolled, 4.9% did not complete PMTCT procedures due to active denial or loss to
follow-up. HIV was first diagnosed in 223 (45.1%) and ART initiated in 321
(65.0%) women during pregnancy. ART was initiated in a median of 1.3 weeks (IQR 0
4.3) after HIV diagnosis. Poor self-reported treatment adherence was higher post
partum than during pregnancy (12.5% vs. 7.0%, P = 0.002) and significantly
associated with divorced/separated marital status (RR 2.2, 95% CI 1.3-3.8), low
family income (RR 2.1, 95% CI 1.1-4.1), low CD4 count (RR 1.7, 95% CI 1.0-3.0)
and ART initiation during delivery (RR 2.5, 95% CI 1.1-5.6). Of 435 infants born
alive, 98.6% received nevirapine prophylaxis. The mother-to-child HIV
transmission rate was 0.7% after a median of 6.7 weeks (IQR 6.4-10.4), but EID
results were received for only 46.6% within 3 months of birth. CONCLUSION: High
retention in PMTCT services, triple maternal ART and high infant nevirapine
prophylaxis coverage were associated with low mother-to-child HIV transmission.
Declining post-partum ART adherence and challenges of EID linkage require
attention.
PMID- 28407453
TI - Stressing Escherichia coli to educate students about research: A CURE to
investigate multiple levels of gene regulation.
AB - Course-based undergraduate research experiences (CUREs) have been shown to
increase student retention and learning in the biological sciences. Most CURES
cover only one aspect of gene regulation, such as transcriptional control. Here
we present a new inquiry-based lab that engages understanding of gene expression
from multiple perspectives. Students carry out a forward genetic screen to
identify regulators of the stationary phase master regulator RpoS in the model
organism Escherichia coli and then use a series of reporter fusions to determine
if the regulation is at the level of transcription or the post-transcription
level. This easy-to-implement course has been run both as a 9-week long project
and a condensed 5-6 week version in three different schools and types of courses.
A majority of the genes found in the screen are novel, thus giving students the
opportunity to contribute to original findings to the field. Assessments of this
CURE show student gains in learning in many knowledge areas. In addition,
attitudinal surveys suggest the students are enthusiastic about the screen and
their learning about gene regulation. In summary, this lab would be an
appropriate addition to an intermediate or advanced level Molecular Biology,
Genetics, or Microbiology curriculum. (c) 2017 by The International Union of
Biochemistry and Molecular Biology, 45(5):449-458, 2017.
PMID- 28407455
TI - Construction and 13 C hyperpolarization efficiency of a 180 GHz dissolution
dynamic nuclear polarization system.
AB - Dynamic nuclear polarization (DNP) via the dissolution method has become one of
the rapidly emerging techniques to alleviate the low signal sensitivity in
nuclear magnetic resonance (NMR) spectroscopy and imaging. In this paper, we
report on the development and 13 C hyperpolarization efficiency of a homebuilt
DNP system operating at 6.423 T and 1.4 K. The DNP hyperpolarizer system was
assembled on a wide-bore superconducting magnet, equipped with a standard
continuous-flow cryostat, and a 180 GHz microwave source with 120 mW power output
and wide 4 GHz frequency tuning range. At 6.423 T and 1.4 K, solid-state 13 C
polarization P levels of 64% and 31% were achieved for 3 M [1-13 C] sodium
acetate samples in 1 : 1 v/v glycerol:water glassing matrix doped with 15 mM
trityl OX063 and 40 mM 4-oxo-TEMPO, respectively. Upon dissolution, which takes
about 15 s to complete, liquid-state 13 C NMR signal enhancements as high as 240
000-fold (P=21%) were recorded in a nearby high resolution 13 C NMR spectrometer
at 1 T and 297 K. Considering the relatively lower cost of our homebuilt DNP
system and the relative simplicity of its design, the dissolution DNP setup
reported here could be feasibly adapted for in vitro or in vivo hyperpolarized 13
C NMR or magnetic resonance imaging at least in the pre-clinical setting.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28407454
TI - Diagnostic criteria for temporomandibular disorders (DC/TMD): interexaminer
reliability of the Finnish version of Axis I clinical diagnoses.
AB - Recently, updated diagnostic criteria for temporomandibular disorders (DC/TMD)
were published to assess TMD in a standardised way in clinical and research
settings. The DC/TMD protocol has been translated into Finnish using specific
cultural equivalency procedures. To assess the interexaminer reliability using
the Finnish translations of the DC/TMD-FIN Axis I clinical diagnostic assessment
instruments. Reliability assessment data were collected during a 1-day DC/TMD
Examiner Training Course at the University of Turku, Finland, in collaboration
with the International DC/TMD Training and Calibration Center in Malmo
University. Clinical TMD examinations according to the Finnish pre-final version
of the DC/TMD Axis I assessment protocol were performed by four experienced TMD
specialists on altogether 16 models. Kappa coefficient, overall percentage
agreement (%A) as well as positive (PA) and negative (NA) agreements were used to
define the reliability. Myofascial pain with referral, headache attributed to TMD
and disc displacement (DD) without reduction without limited opening showed
excellent kappa values (range 0.87-1.00). Fair-to-good reliability was observed
for diagnoses of myalgia (k = 0.67), arthralgia (k = 0.71) and DD with reduction
(k = 0.64). The PA was high for all pain-related diagnoses and DD without
reduction without limited opening (medians >=83%), and acceptable for DD with
reduction (median 67%). The NA was high (medians >=87%) for all DC/TMD diagnoses,
except for myalgia which showed acceptable NA (median 75%). The %A was high for
all assessed diagnoses (medians >85%). The findings of this study showed DC/TMD
FIN Axis I to demonstrate sufficiently high reliability for pain-related TMD
diagnoses.
PMID- 28407456
TI - 3-Nitro-2-pyridinesulfenates as Efficient Solution- and Solid-Phase Disulfide
Bond Forming Agents.
AB - In this paper, a new disulfide-forming agent based on the finding that alkoxy 3
nitro-2-pyridinesulfenates (Npys-OR) can oxidize thiol groups is reported. Methyl
3-nitro-2-pyridinesulfenate (Npys-OMe), which is easily prepared from 3-nitro-2
pyridinesulfenyl chloride in a one-step reaction and has a reduction peak
potential (Epc ) of -0.541 V versus Ag/AgCl, produces the cyclic nonapeptide
oxytocin from its linear form in good yield (92 %) with minimal oligomer
formation. Npys-OMe in the solid phase also demonstrated excellent results in
oxytocin synthesis. Other disulfide-containing peptides, such as alpha-human
atrial natriuretic peptide and alpha-conotoxin ImI, were also successfully
synthesized. During these syntheses, no side reactions of methionine (Met) and
tryptophan (Trp) residues or the S-acetamidomethyl (Acm) protecting group were
detected. These results suggested that Npys-OMe or its solid-phase analog
provides a new strategy for regioselective disulfide bond formation to assist the
synthesis of complex disulfide-rich peptides.
PMID- 28407457
TI - Dynamics of sediment carbon stocks across intertidal wetland habitats of Moreton
Bay, Australia.
AB - Coastal wetlands are known for high carbon storage within their sediments, but
our understanding of the variation in carbon storage among intertidal habitats,
particularly over geomorphological settings and along elevation gradients, is
limited. Here, we collected 352 cores from 18 sites across Moreton Bay,
Australia. We assessed variation in sediment organic carbon (OC) stocks among
different geomorphological settings (wetlands within riverine settings along with
those with reduced riverine influence located on tide-dominated sand islands),
across elevation gradients, with distance from shore and among habitat and
vegetation types. We used mid-infrared (MIR) spectroscopy combined with
analytical data and partial least squares regression to quantify the carbon
content of ~2500 sediment samples and provide fine-scale spatial coverage of
sediment OC stocks to 150 cm depth. We found sites in river deltas had larger OC
stocks (175-504 Mg/ha) than those in nonriverine settings (44-271 Mg/ha).
Variation in OC stocks among nonriverine sites was high in comparison with
riverine and mixed geomorphic settings, with sites closer to riverine outflow
from the east and south of Moreton Bay having higher stocks than those located on
the sand islands in the northwest of the bay. Sediment OC stocks increased with
elevation within nonriverine settings, but not in riverine geomorphic settings.
Sediment OC stocks did not differ between mangrove and saltmarsh habitats. OC
stocks did, however, differ between dominant species across the research area and
within geomorphic settings. At the landscape scale, the coastal wetlands of the
South East Queensland catchments (17,792 ha) are comprised of approximately
4,100,000-5,200,000 Mg of sediment OC. Comparatively high variation in OC storage
between riverine and nonriverine geomorphic settings indicates that the
availability of mineral sediments and terrestrial derived OC may exert a strong
influence over OC storage potential across intertidal wetland systems.
PMID- 28407458
TI - Ultrasound anal sphincter defects and 3D anal pressure defects.
PMID- 28407459
TI - Enhanced Stability and Tunable Photoluminescence in Perovskite CsPbX3 /ZnS
Quantum Dot Heterostructure.
AB - All-inorganic perovskite CsPbX3 (X = Cl, Br, I) and related materials are
promising candidates for potential solar cells, light emitting diodes, and
photodetectors. Here, a novel architecture made of CsPbX3 /ZnS quantum dot
heterodimers synthesized via a facile solution-phase process is reported.
Microscopic measurements show that CsPbX3 /ZnS heterodimer has high crystalline
quality with enhanced chemical stability, as also evidenced by systematic density
functional theory based first-principles calculations. Remarkably, depending on
the interface structure, ZnS induces either n-type or p-type doping in CsPbX3 and
both type-I and type-II heterojunctions can be achieved, leading to rich
electronic properties. Photoluminescence measurement results show a strong blue
shift and decrease of recombination lifetime with increasing sulfurization, which
is beneficial for charge diffusion in solar cells and photovoltaic applications.
These findings are expected to shed light on further understanding and design of
novel perovskite heterostructures for stable, tunable optoelectronic devices.
PMID- 28407460
TI - Depressive Symptoms and Their Interactions With Emotions and Personality Traits
Over Time: Interaction Networks in a Psychiatric Clinic.
AB - Objective: Associations between depression, personality traits, and emotions are
complex and reciprocal. The aim of this study is to explore these interactions in
dynamical networks and in a linear way over time depending on the severity of
depression. Methods: Participants included 110 patients with depressive symptoms
(DSM-5 criteria) who were recruited between October 2015 and February 2016 during
their inpatient stay in a general psychiatric hospital in Hall in Tyrol, Austria.
The patients filled out the Beck Depression Inventory-II, a German emotional
competence questionnaire (Emotionale Kompetenz Fragebogen), Positive and Negative
Affect Schedule, and the German versions of the Big Five Inventory-short form and
State-Trait-Anxiety-Depression Inventory regarding symptoms, emotions, and
personality during their inpatient stay and at a 3-month follow-up by mail.
Network and regression analyses were performed to explore interactions both in a
linear and a dynamical way at baseline and 3 months later. Results: Regression
analyses showed that emotions and personality traits gain importance for the
prediction of depressive symptoms with decreasing symptomatology at follow-up
(personality: baseline, adjusted R2 = 0.24, P < .001; follow-up, adjusted R2 =
0.65, P < .001). Network analyses additionally showed that the interaction
network of depression, emotions, and personality traits is significantly denser
and more interconnected (network comparison test: P = .03) at follow-up than at
baseline, meaning that with decreased symptoms interconnections get stronger.
Conclusions: During depression, personality traits and emotions are walled off
and not strongly interconnected with depressive symptoms in networks. With
decreasing depressive symptomatology, interfusing of these areas begins and
interconnections become stronger. This finding has practical implications for
interventions in an acute depressive state and with decreased symptoms. The
network approach offers a new perspective on interactions and is a way to make
the complexity of these interactions more tangible.
PMID- 28407461
TI - The Biological Basis to Personality Disorders.
AB - Objective: To provide understanding into the biological basis of thinking and
behavior in people with personality disorders, explain anatomic findings, and
appraise therapeutic options. Data Sources: PubMed was searched with no date
restrictions using the terms personality disorders DSM-5, cluster B personality
disorders, biological psychiatry of personality disorders, neurobiology of
personality disorders, and neurobiology of cluster B personality disorders. Study
Selection/Data Extraction: We identified 2,790 English-language articles and
utilized 18 in this report. Results: There are anatomic features typical to the
brains of individuals with cluster B personality disorders, for example,
abnormalities in the superior frontal cortex and amygdala and enlarged striatal
volumes. Emotional dysregulation and impulsiveness are 2 prominent symptoms.
Hereditary factors may contribute to the development of such conditions.
Conclusion: Understanding the neurobiology of cluster B personality disorders
expands knowledge that hopefully results in better clinical management and
development of improved treatments. Psychotherapy is currently the most effective
intervention for borderline personality disorders. Symptomatic pharmacotherapies
may be prescribed adjunctively on an individualized basis if clinically indicated
(eg, with a coexistant depression).
PMID- 28407462
TI - Overexpression of POSTN in Tumor Stroma Is a Poor Prognostic Indicator of
Colorectal Cancer.
AB - BACKGROUND: Tumor microenvironment has recently drawn attention in that it is
related with tumor prognosis. Cancer-associated fibroblast also plays a critical
role in cancer invasiveness and progression in colorectal cancers. Periostin
(POSTN), originally identified to be expressed in osteoblasts and osteoblast
derived cells, is expressed in cancer-associated fibroblasts in several tissue
types of cancer. Recent studies suggest an association between stromal
overexpression of POSTN and poor prognosis of cancer patients. METHODS: We
analyzed colorectal cancer cases for their expression status of POSTN in tumor
stroma using immunohistochemistry and correlated the expression status with
clinicopathological and molecular features. RESULTS: High level of POSTN
expression in tumor stroma was closely associated with tumor location in proximal
colon, infiltrative growth pattern, undifferentiated histology, tumor budding,
luminal necrosis, and higher TNM stage. High expression status of POSTN in tumor
stroma was found to be an independent prognostic parameter implicating poor 5
year cancer-specific survival and 5-year progression-free survival. CONCLUSIONS:
Our findings suggest that POSTN overexpression in tumor stroma of colorectal
cancers could be a possible candidate marker for predicting poor prognosis in
patients with colorectal cancers.
PMID- 28407463
TI - Number of existing permanent teeth is associated with chronic kidney disease in
the elderly Korean population.
AB - BACKGROUND/AIMS: The aim of this study was to assess the association between the
number of existing permanent teeth and chronic kidney disease (CKD) in a
representative sample of the elderly Korean population. METHODS: A total of 2,519
subjects who participated in the Korean National Health and Nutrition Examination
Survey were cross-sectionally examined. The number of existing permanent teeth
was evaluated by clinical oral examination. CKD was defined based on definition
and classification by Kidney Disease: Improving Global Outcomes (KDIGO) 2012
guidelines. Multivariable logistic regression analyses were performed controlling
for age, gender, income, education, tooth-brushing frequency, periodontitis,
state of dentition, smoking, alcohol consumption, hypertension, obesity, diabetes
mellitus, and hypercholesterolemia. Subgroup analyses by age and gender were also
performed. RESULTS: The number of teeth was significantly associated with CKD
after controlling for all potential confounders (adjusted odds ratio [AOR], 1.67;
95% confidence interval [CI], 1.04 to 2.70 for lower number of teeth; AOR, 1.59;
95% CI, 1.14 to 2.23 for moderate number of teeth). In the subgroup analyses, the
association was highlighted in females aged 75 years over (AOR, 2.55; 95% CI,
1.05 to 6.20 for lower number of teeth; AOR, 1.95; 95% CI, 1.01 to 3.80 for
moderate number of teeth). CONCLUSION: Our findings suggest that the number of
existing permanent teeth may be associated with CKD among Korean elderly.
PMID- 28407465
TI - KRAS G12C mutation as a poor prognostic marker of pemetrexed treatment in non
small cell lung cancer.
AB - BACKGROUND/AIMS: The predictive and prognostic value of KRAS mutation and its
type of mutations in non-small cell lung cancer (NSCLC) are controversial. This
clinical study was designed to investigate the predictive value of KRAS mutations
and its mutation types to pemetrexed and gemcitabine based treatment. METHODS:
Advanced NSCLC patients tested for KRAS mutation (n = 334) were retrospectively
reviewed and 252 patients with wild type epidermal growth factor receptor and no
anaplastic lymphoma kinase fusion were enrolled for the analysis. KRAS mutations
were observed in 45 subjects with mutation type as followed: G12C (n = 13), G12D
(n = 12), G12V (n = 12), other (n = 8). Response rate (RR), progression-free
survival (PFS), and overall survival (OS) of pemetrexed singlet and gemcitabine
based chemotherapy were analysis. RESULTS: Age, sex, performance status were well
balanced between subjects with or without KRAS mutations. No difference was
observed in RR. Hazard ratio (HR) of PFS for pemetrexed treated subjects with
G12C mutation compared to subjects with KRAS wild type was 1.96 (95% confidential
interval [CI], 1.01 to 3.79; p = 0.045), but other mutations failed to show
clinical significance. By analysis done by PFS, compared to the subjects with
transition mutation, HR was 1.48 (95% CI, 0.64 to 3.40; p = 0.360) for subjects
with transversion mutation on pemetrexed treatment and 0.41 (95% CI, 0.19 to
0.87; p = 0.020) for subjects treated with gemcitabine based chemotherapy. No
difference was observed in OS. CONCLUSIONS: In this study, different drug
sensitivity was observed according to the type of KRAS mutation. NSCLC
subpopulations with different KRAS mutation type should be considered as
different subgroups and optimal chemotherapy regimens should be searched in
further confirmative studies.
PMID- 28407464
TI - Practical management of peripartum cardiomyopathy.
AB - Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy that causes
systolic heart failure (HF) in previously healthy young women. Despite latest
remarkable achievement, unifying pathophysiologic mechanism is not well
established. Considering close temporal relationship to pregnancy, the recent
prolactin theory is promising. Abnormal short form of 16-kDa prolactin may be
produced in the oxidative stress milieu, show anti-angiogenic effect and damage
cardiovascular structure in late pregnancy. Future study is needed to determine
whether abnormal prolactin system is useful as a biomarker for diagnosis and
therapy of PPCM. Diagnosis is made based on the finding of left ventricular
systolic dysfunction after excluding other causes of HF. A multidisciplinary team
approach is essential for acute HF, antepartum, labor and postpartum care.
Recovery from left ventricular dysfunction is critical for prognosis. As PPCM can
recur and cause serious clinical events, subsequent pregnancy is not recommended.
This review focuses on the practical management of PPCM.
PMID- 28407466
TI - CO-Reduction Chemistry: Reaction of a CO-Derived Formylhydridoborate with Carbon
Monoxide, with Carbon Dioxide, and with Dihydrogen.
AB - Treatment of the bulky metallocene hydride Cp*2Zr(H)OMes (Cp* =
pentamethylcyclopentadienyl, Mes = mesityl) with Piers' borane [HB(C6F5)2] and
carbon monoxide (CO) gave the formylhydridoborate complex [Zr]-O?CH-BH(C6F5)2
([Zr] = Cp*2Zr-OMes). From the dynamic NMR behavior, its endergonic equilibration
with the [Zr]-O-CH2-B(C6F5)2 isomer was deduced, which showed typical reactions
of an oxygen/boron frustrated Lewis pair. It was trapped with CO to give an O
[Zr] bonded borata-beta-lactone. Trapping with carbon dioxide (CO2) gave the
respective O-[Zr] bonded cyclic boratacarbonate product. These reaction pathways
were analyzed by density functional theory calculation. The formylhydridoborate
complex was further reduced by dihydrogen via two steps; it reacted rapidly with
H2 to give Cp*2Zr(OH)OMes and H3C-B(C6F5)2, which then slowly reacted further
with H2 to eventually give [Zr]-O(H)-B(H)(C6F5)2 and methane (CH4). Most
complexes were characterized by X-ray diffraction.
PMID- 28407467
TI - Trace Uranium Partitioning in a Multiphase Nano-FeOOH System.
AB - The characterization of trace elements in minerals using extended X-ray
absorption fine structure (EXAFS) spectroscopy constitutes a first step toward
understanding how impurities and contaminants interact with the host phase and
the environment. However, limitations to EXAFS interpretation complicate the
analysis of trace concentrations of impurities that are distributed across
multiple phases in a heterogeneous system. Ab initio molecular dynamics (AIMD)
informed EXAFS analysis was employed to investigate the immobilization of trace
uranium associated with nanophase iron (oxyhydr)oxides, a model system for the
geochemical sequestration of radiotoxic actinides. The reductive transformation
of ferrihydrite [Fe(OH)3] to nanoparticulate iron oxyhydroxide minerals in the
presence of uranyl (UO2)2+(aq) resulted in the preferential incorporation of U
into goethite (alpha-FeOOH) over lepidocrocite (gamma-FeOOH), even though
reaction conditions favored the formation of excess lepidocrocite. This
unexpected result is supported by atomically resolved transmission electron
microscopy. We demonstrate how AIMD-informed EXAFS analysis lifts the strict
statistical limitations and uncertainty of traditional shell-by-shell EXAFS
fitting, enabling the detailed characterization of the local bonding environment,
charge compensation mechanisms, and oxidation states of polyvalent impurities in
complex multiphase mineral systems.
PMID- 28407469
TI - Electronic Levels of Excess Electrons in Liquid Water.
AB - We provide a consistent description of the electronic levels associated with
localized and delocalized excess electrons in liquid water by combining hybrid
functional molecular dynamics simulations with a grand canonical formulation of
solutes in aqueous solution. The excess electron localizes in a cavity with an
average radius of 1.8 A and a majority coordination of five water molecules. The
vertical binding energy, the optical s-p transitions, and the adiabatic redox
level are found to agree closely with their experimental counterparts. The energy
level associated with electron delocalization V0 is inferred to lie at -0.97 eV
with respect to the vacuum level.
PMID- 28407468
TI - Thiol Specific and Tracelessly Removable Bioconjugation via Michael Addition to 5
Methylene Pyrrolones.
AB - 5-Methylene pyrrolones (5MPs) are highly thiol-specific and tracelessly removable
bioconjugation tools. 5MPs are readily prepared from primary amines in one step.
5MPs exhibit significantly improved stability under physiologically relevant
conditions and cysteine specificity compared to commonly used analogues,
maleimides. Michael addition of thiol to 5MPs occurs rapidly, cleanly, and does
not generate a stereocenter. The conjugates efficiently release thiols via retro
Michael reaction in alkaline buffer (pH 9.5) or via thiol exchange at pH 7.5.
This unique property makes 5MPs valuable for the controlled release of conjugated
cargo and temporary thiol protection. The utilization of 5MPs for protein
immobilization and pull-down of active complexes is illustrated using E. coli.
acetohydroxyacid synthase isozyme I.
PMID- 28407470
TI - Label-Free Vibrational Spectroscopic Imaging of Neuronal Membrane Potential.
AB - Detecting membrane potentials is critical for understanding how neuronal networks
process information. We report a vibrational spectroscopic signature of neuronal
membrane potentials identified through hyperspectral stimulated Raman scattering
(SRS) imaging of patched primary neurons. High-speed SRS imaging allowed direct
visualization of puff-induced depolarization of multiple neurons in mouse brain
slices, confirmed by simultaneous calcium imaging. The observed signature,
partially dependent on sodium ion influx, is interpreted as ion interactions on
the CH3 Fermi resonance peak in proteins. By implementing a dual-SRS balanced
detection scheme, we detected single action potentials in electrically stimulated
neurons. These results collectively demonstrate the potential of sensing neuronal
activities at multiple sites with a label-free vibrational microscope.
PMID- 28407471
TI - Lithium Bis(fluorosulfonyl)imide/Poly(ethylene oxide) Polymer Electrolyte for All
Solid-State Li-S Cell.
AB - Solid polymer electrolytes (SPEs) comprising lithium bis(fluorosulfonyl)imide
(Li[N(SO2F)2], LiFSI) and poly(ethylene oxide) (PEO) have been studied as
electrolyte material and binder for the Li-S polymer cell. The LiFSI-based Li-S
all solid polymer cell can deliver high specific discharge capacity of 800 mAh
gsulfur-1 (i.e., 320 mAh gcathode-1), high areal capacity of 0.5 mAh cm-2, and
relatively good rate capability. The cycling performances of Li-S polymer cell
with LiFSI are significantly improved compared with those with conventional
LiTFSI (Li[N(SO2CF3)2]) salt in the polymer membrane due to the improved
stability of the Li anode/electrolyte interphases formed in the LiFSI-based SPEs.
These results suggest that the LiFSI-based SPEs are attractive electrolyte
materials for solid-state Li-S batteries.
PMID- 28407472
TI - Introduction to the Centers for Disease Control and Prevention and Healthcare
Infection Control Practices Advisory Committee Guideline for Prevention of
Surgical Site Infection: Prosthetic Joint Arthroplasty Section.
AB - Peri-prosthetic joint infection (PJI) is a severe complication of total joint
arthroplasty that appears to be increasing as more of these procedures are
performed. Numerous risk factors for incisional (superficial and deep) and
organ/space (e.g., PJI) surgical site infections (SSIs) have been identified. A
better understanding and reversal of modifiable risk factors may lead to a
reduction in the incidence of incisional SSI and PJI. The Centers for Disease
Control and Prevention (CDC) and the Healthcare Infection Control Practices
Advisory Committee (HICPAC) recently updated the national Guideline for
Prevention of Surgical Site Infection. The updated guideline applies evidence
based methodology, presents recommendations for potential strategies to reduce
the risk of SSI, and includes an arthroplasty-specific section. This article
serves to introduce the guideline development process and to complement the
Prosthetic Joint Arthroplasty section with background information on PJI-specific
economic burden, epidemiology, pathogenesis and microbiology, and risk factor
information.
PMID- 28407473
TI - Trimodal rescue of hind limb ischemia with growth factors, cells, and
nanocarriers: fundamentals to clinical trials.
AB - Peripheral artery disease is a severe medical condition commonly characterized by
critical or acute limb ischemia. Gradual accumulation of thrombotic plaques in
peripheral arteries of the lower limb may lead to intermittent claudication or
ischemia in muscle tissue. Ischemic muscle tissue with lesions may become
infected, resulting in a non-healing wound. Stable progression of the non-healing
wound associated with severe ischemia might lead to functional deterioration of
the limb, which, depending on the severity, can result in amputation. Immediate
rescue of ischemic muscles through revascularization strategies is considered the
gold standard to treat critical limb ischemia. Growth factors offer multiple
levels of protection in revascularization of ischemic tissue. In this review, the
basic mechanism through which growth factors exert their beneficial properties to
rescue the ischemic limb is extensively discussed. Moreover, clinical trials
based on growth factor and stem cell therapy to treat critical limb ischemia are
considered. The clinical utility of stem cell therapy for the treatment of limb
ischemia is explained and recent advances in nanocarrier technology for selective
growth factor and stem cell supplementation are summarized.
PMID- 28407474
TI - The impact of low and no-caloric sweeteners on glucose absorption, incretin
secretion, and glucose tolerance.
AB - The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is
increasing globally. Previously thought to be physiologically inert, there is a
growing body of evidence that LCS not only provide a sweet taste but may also
elicit metabolic effects in the gastrointestinal tract. This review provides a
brief overview of the chemical and receptor-binding properties and effects on
chemosensation of different LCS but focuses on the extent to which LCS stimulates
glucose transport, incretin and insulin secretion, and effects on glucose
tolerance. Aspartame and sucralose both bind to a similar region of the sweet
receptor. For sucralose, the data are contradictory regarding effects on glucose
tolerance in humans and may depend on the food or beverage matrix and the
duration of administration, as suggested by longer term rodent studies. For
aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K)
and saccharin have similar binding characteristics to each other but, while Ace-K
may increase incretin secretion and glucose responses in humans, there are no
data on saccharin except in rats, which show impaired glucose tolerance after
chronic administration. Additional research, particularly of the effects of
chronic consumption, is needed to provide concrete evidence for beneficial or
detrimental effects of LCS on blood glucose regulation in humans.
PMID- 28407475
TI - Fungal endophytes of wild and hybrid Vitis leaves and their potential for
vineyard biocontrol.
AB - Plants are colonized by diverse assemblages of fungal endophytes that have
potential as biocontrol agents for a variety of crops, including grapevine.
Although the diversity of symbionts can be very high in wild plants, the fungal
endophytes of wild Vitis plants have not yet been investigated. We surveyed the
fungal endophytes of 6 wild populations of Vitis riparia, as well as a cold
tolerant, hybrid grapevine in 5 vineyards (1 certified organic), using 454
pyrosequencing. We detected between 43 and 235 operational taxonomic units per
sample, with the highest richness and diversity in the wild, the lowest in
conventional vineyards, and intermediate levels in the organic vineyard. Wild
plants supported a range of taxa not seen in the conventional vineyards, and
vineyards were dominated by relatively few taxa. We also isolated fungi from the
wild plants and tested them for their ability to inhibit pathogens of grapevine.
Several wild isolates (e.g., Ramularia spp.) were strongly inhibitory to
grapevine pathogens. We show that wild Vitis supports a distinct and highly
diverse community of fungal endophytes and may represent a rich repository of
potential vineyard biocontrol agents.
PMID- 28407476
TI - Measurement of sodium concentration in sweat samples: comparison of 5 analytical
techniques.
AB - Sweat sodium concentration (SSC) can be determined using different analytical
techniques (ATs), which may have implications for athletes and scientists. This
study compared the SSC measured with 5 ATs: ion chromatography (IChr), flame
photometry (FP), direct (DISE) and indirect (IISE) ion-selective electrode, and
ion conductivity (IC). Seventy sweat samples collected from 14 athletes were
analyzed with 5 instruments: the 883 Basic IC Plus (IChr, reference instrument),
AAnalyst 200 (FP), Cobas 6000 (IISE), Sweat-Chek (IC), and B-722 Laqua Twin
(DISE). Instruments showed excellent relative (intraclass correlation coefficient
(ICC) >= 0.999) and absolute (coefficient of variation (CV) <= 2.6%) reliability.
Relative validity was also excellent between ATs (ICC >= 0.961). In regards to
the inter-AT absolute validity, compared with IChr, standard error of the
estimates were similar among ATs (2.8-3.8 mmol/L), but CV was lowest with DISE
(3.9%), intermediate with IISE (7.6%), and FP (6.9%) and highest with IC (12.3%).
In conclusion, SSC varies depending on the AT used to analyze samples. Therefore,
results obtained from different ATs are scarcely comparable and should not be
used interchangeably. Nevertheless, taking into account the normal variability in
SSC (~+/-12%), the imprecision of the recommendations deriving from FP, IISE, IC,
and DISE should have trivial health and physiological consequences under most
exercise circumstances.
PMID- 28407477
TI - A RIPtide Protects Neurons from Infection.
AB - RIPK3 and RIPK1 limit virus spread by executing either apoptotic or necroptotic
cell death in response to infection. In a recent issue of Cell, Daniels et al.
(2017) unveil an unexpected cell death-independent requirement of RIP kinase
activity in coordinating neuroinflammation, restricting West Nile virus
pathogenesis in neurons.
PMID- 28407478
TI - Breaking Down Walls: Microbiota and the Aging Gut.
AB - A range of animal species show increased inflammation with age. In this issue of
Cell Host & Microbe, Thevaranjan et al. (2017) reveal that heightened
inflammation is associated with deregulation of homeostatic interactions between
intestinal microbes and the aging host.
PMID- 28407479
TI - Living in Peace: Host-Microbiota Mutualism in the Skin.
AB - Commensal microbes colonize the skin where they promote immune development and
prevent infection without inducing damaging inflammatory responses. In this issue
of Cell Host & Microbe, Scharschmidt et al. (2017) show that during hair follicle
development, commensals induce regulatory T cell migration to the skin to ensure
cutaneous homeostasis.
PMID- 28407480
TI - The Landscape Ecology and Microbiota of the Human Nose, Mouth, and Throat.
AB - Landscape ecology examines the relationships between the spatial arrangement of
different landforms and the processes that give rise to spatial and temporal
patterns in local community structure. The spatial ecology of the microbial
communities that inhabit the human body-in particular, those of the nose, mouth,
and throat-deserves greater attention. Important questions include what defines
the size of a population (i.e., "patch") in a given body site, what defines the
boundaries of distinct patches within a single body site, and where and over what
spatial scales within a body site are gradients detected. This Review looks at
the landscape ecology of the upper respiratory tract and mouth and seeks greater
clarity about the physiological factors-whether immunological, chemical, or
physical-that govern microbial community composition and function and the
ecological traits that underlie health and disease.
PMID- 28407482
TI - Salmonella Typhimurium Diarrhea Reveals Basic Principles of Enteropathogen
Infection and Disease-Promoted DNA Exchange.
AB - Despite decades of research, efficient therapies for most enteropathogenic
bacteria are still lacking. In this review, we focus on Salmonella enterica
Typhimurium (S. Typhimurium), a frequent cause of acute, self-limiting food-borne
diarrhea and a model that has revealed key principles of enteropathogen
infection. We review the steps of gut infection and the mucosal innate-immune
defenses limiting pathogen burdens, and we discuss how inflammation boosts gut
luminal S. Typhimurium growth. We also discuss how S. Typhimurium-induced
inflammation accelerates the transfer of plasmids and phages, which may promote
the transmission of antibiotic resistance and facilitate emergence of pathobionts
and pathogens with enhanced virulence. The targeted manipulation of the
microbiota and vaccination might offer strategies to prevent this evolution. As
gut luminal microbes impact various aspects of the host's physiology, improved
strategies for preventing enteropathogen infection and disease-inflicted DNA
exchange may be of broad interest well beyond the acute infection.
PMID- 28407481
TI - The Gut Microbiome: Connecting Spatial Organization to Function.
AB - The first rudimentary evidence that the human body harbors a microbiota hinted at
the complexity of host-associated microbial ecosystems. Now, almost 400 years
later, a renaissance in the study of microbiota spatial organization, driven by
coincident revolutions in imaging and sequencing technologies, is revealing
functional relationships between biogeography and health, particularly in the
vertebrate gut. In this Review, we present our current understanding of
principles governing the localization of intestinal bacteria, and spatial
relationships between bacteria and their hosts. We further discuss important
emerging directions that will enable progressing from the inherently descriptive
nature of localization and -omics technologies to provide functional,
quantitative, and mechanistic insight into this complex ecosystem.
PMID- 28407483
TI - Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic
Inflammation, and Macrophage Dysfunction.
AB - Levels of inflammatory mediators in circulation are known to increase with age,
but the underlying cause of this age-associated inflammation is debated. We find
that, when maintained under germ-free conditions, mice do not display an age
related increase in circulating pro-inflammatory cytokine levels. A higher
proportion of germ-free mice live to 600 days than their conventional
counterparts, and macrophages derived from aged germ-free mice maintain anti
microbial activity. Co-housing germ-free mice with old, but not young,
conventionally raised mice increases pro-inflammatory cytokines in the blood. In
tumor necrosis factor (TNF)-deficient mice, which are protected from age
associated inflammation, age-related microbiota changes are not observed.
Furthermore, age-associated microbiota changes can be reversed by reducing TNF
using anti-TNF therapy. These data suggest that aging-associated microbiota
promote inflammation and that reversing these age-related microbiota changes
represents a potential strategy for reducing age-associated inflammation and the
accompanying morbidity.
PMID- 28407484
TI - Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal
Carcinogenesis.
AB - Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
(APECED), a T cell-driven autoimmune disease caused by impaired central
tolerance, are susceptible to chronic fungal infection and esophageal squamous
cell carcinoma (ESCC). However, the relationship between autoreactive T cells and
chronic fungal infection in ESCC development remains unclear. We find that kinase
dead Ikkalpha knockin mice develop APECED-like phenotypes, including impaired
central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs
expressing specific human ESCC markers. Using this model, we investigated the
link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal
infection and incite tissue injury and inflammation. Antifungal treatment or
autoreactive CD4 T cell depletion rescues, whereas oral fungal administration
promotes, ESCC development. Inhibition of inflammation or epidermal growth factor
receptor (EGFR) activity decreases fungal burden. Fungal infection is highly
associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T
cells and chronic fungal infection, fostered by inflammation and epithelial
injury, promote ESCC development.
PMID- 28407485
TI - Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T
Lymphocytes, which Shape the Proviral Landscape.
AB - Despite antiretroviral therapy, HIV-1 persists in memory CD4+ T cells, creating a
barrier to cure. The majority of HIV-1 proviruses are defective and considered
clinically irrelevant. Using cells from HIV-1-infected individuals and
reconstructed patient-derived defective proviruses, we show that defective
proviruses can be transcribed into RNAs that are spliced and translated.
Proviruses with defective major splice donors (MSDs) can activate novel splice
sites to produce HIV-1 transcripts, and cells with these proviruses can be
recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs). Further, cells with
proviruses containing lethal mutations upstream of CTL epitopes can also be
recognized by CTLs, potentially through aberrant translation. Thus, CTLs may
change the landscape of HIV-1 proviruses by preferentially targeting cells with
specific types of defective proviruses. Additionally, the expression of defective
proviruses will need to be considered in the measurement of HIV-1 latency
reversal.
PMID- 28407487
TI - Matching NLR Immune Receptors to Autoimmunity in camta3 Mutants Using Antimorphic
NLR Alleles.
AB - To establish infection, pathogens deploy effectors to modify or remove host
proteins. Plant immune receptors with nucleotide-binding, leucine-rich repeat
domains (NLRs) detect these modifications and trigger immunity. Plant NLRs thus
guard host "guardees." A corollary is that autoimmunity may result from
inappropriate NLR activation because mutations in plant guardees could trigger
corresponding NLR guards. To explore these hypotheses, we expressed 108 dominant
negative (DN) Arabidopsis NLRs in various lesion mimic mutants, including camta3,
which exhibits autoimmunity. CAMTA3 was previously described as a negative
regulator of immunity, and we find that autoimmunity in camta3 is fully
suppressed by expressing DNs of two NLRs, DSC1 and DSC2. Additionally, expression
of either NLR triggers cell death that can be suppressed by CAMTA3 expression.
These findings support a model in which DSC1 and DSC2 guard CAMTA3, and they
suggest that other negative regulators of immunity may similarly represent
guardees.
PMID- 28407488
TI - The Matrix Protein of Human Parainfluenza Virus Type 3 Induces Mitophagy that
Suppresses Interferon Responses.
AB - Mitophagy is a form of autophagy that selectively removes damaged mitochondria.
Impaired mitochondria can be tagged by the kinase PINK1, which triggers
recruitment of the E3-ubiquitin ligase Parkin and subsequent mitochondrial
sequestration within autophagosomes. We previously found that human parainfluenza
virus type 3 (HPIV3) infection induces autophagy, but the type and mechanisms of
autophagy induction remain unknown. Here, we show that matrix protein (M) of
HPIV3 translocates to mitochondria and interacts with Tu translation elongation
factor mitochondrial (TUFM). M-mediated mitophagy does not require the Parkin
PINK1 pathway but rather an interaction between M and the LC3 protein that
mediates autophagosome formation. These interactions with both TUFM and LC3 are
required for the induction of mitophagy and lead to inhibition of the type I
interferon response. These results reveal that a viral protein is sufficient to
induce mitophagy by bridging autophagosomes and mitochondria.
PMID- 28407486
TI - Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation
Complex Drives Lytic Infection and Reactivation from Latency.
AB - The cellular transcriptional coactivator HCF-1 is required for initiation of
herpes simplex virus (HSV) lytic infection and for reactivation from latency in
sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer
complex and mediates chromatin transitions to promote IE transcription
initiation. In infected cells, HCF-1 was also found to be associated with a
network of transcription elongation components including the super elongation
complex (SEC). IE genes exhibit characteristics of genes controlled by
transcriptional elongation, and the SEC-P-TEFb complex is specifically required
to drive the levels of productive IE mRNAs. Significantly, compounds that enhance
the levels of SEC-P-TEFb also potently stimulated HSV reactivation from latency
both in a sensory ganglia model system and in vivo. Thus, transcriptional
elongation of HSV IE genes is a key limiting parameter governing both the
initiation of HSV infection and reactivation of latent genomes.
PMID- 28407489
TI - Exposure to the plasticizer di(2-ethylhexyl) terephthalate (DEHTP) in Portuguese
children - Urinary metabolite levels and estimated daily intakes.
AB - Classical ortho-phthalate plasticizers are, due to their endocrine disrupting
potency and reproductive toxicity, increasingly replaced by alternative
plasticizers. Di(2-ethylhexyl) terephthalate (DEHTP) is one of these substitutes.
In this study, we investigated DEHTP exposure in 107 Portuguese children (4
17years old) by analyzing specific DEHTP metabolites in their urine using a newly
developed LC-MS/MS method. We could detect the major, specific DEHTP metabolite
mono(2-ethyl-5-carboxypentyl) terephthalate (5cx-MEPTP) in 100% of the samples
with levels above the limit of quantification in 96% of the samples (median
concentration 4.19MUg/L; 95th percentile 26.4MUg/L; maximum 3400MUg/L). Other
minor DEHTP metabolites (5OH-MEHTP, 5oxo-MEHTP and 2cx-MMHTP) were detected at
lower rates and levels. Daily DEHTP intakes calculated from urinary 5cx-MEPTP
levels were generally far below the tolerable daily intake (TDI) of
1000MUg/kgbw/d (median 0.67MUg/kgbw/d; 95th percentile 6.25MUg/kgbw/d; maximum
690MUg/kgbw/d). However, for one child the biomarker-derived health-based
guidance value (HBM-I value) for 5cx-MEPTP of 1800MUg/L was exceeded by about a
factor of two. Levels of 5cx-MEPTP and calculated daily DEHTP intakes were higher
in normal/under-weight children who nourished on their usual diet compared to
overweight/obese children who received nutritional guidance with fresh and
unprocessed food (p=0.043 and p<0.001 respectively). This indicates to processed
and fatty foodstuff as a major source of DEHTP exposure. Additionally, we found
children of lower age having higher DEHTP intakes (p=0.045). Again, foodstuff as
a major DEHTP source, together with other child specific DEHTP sources such as
mouthing of toys or ingestion of dust might be contributing factors. With the
present study, we provide a first data set on the omnipresent DEHTP exposure in
children. So far, general levels of DEHTP exposure seem no cause for concern.
However, due to the increasing use of DEHTP as an ortho-phthalate substitute,
possible increasing exposures in the future should be followed closely.
PMID- 28407490
TI - CO2 effects on the waterlogging response of 'Gisela 5' and 'Gisela 6' (Prunus
cerasusxPrunus canescens) sweet cherry (Prunus avium) rootstocks.
AB - Climate change is submitting countries of the Mediterranean arc to periods of
drought alternating with heavy rain and waterlogging. Eventual floods along with
the rising CO2 in the atmosphere present an unpredictable scenario that affects
crop survival. The effect of both stresses combined has been studied in sweet
cherry plants. 'Gisela 5' and 'Gisela 6' were evaluated as rootstocks of the
sweet cherry cultivar 'Burlat'. Plants were placed in a controlled-climate
chamber for 7days, then they were submitted to waterlogging for another 7days and
the response to this stress and the subsequent recovery were studied (7 more
days). The experiment was carried out at 400MUmolmol-1 CO2 (ambient CO2) and
800MUmolmol-1 CO2, at 26 degrees C, and plant water status and growth, net CO2
assimilation, transpiration, stomatal conductance, water potential, chlorophyll
fluorescence, relative water content, anions content, proline, lipid
peroxidation, soluble sugars, and starch were measured. Differences in the
response and in its intensity were detected in both rootstocks. Some parameters -
such as photosynthesis, soluble sugars, starch, TBARS, and NO3- - varied
depending on the CO2 conditions and the waterlogging effect. Elevated CO2 was
able to increase photosynthesis and thereby help plants to overcome waterlogging.
PMID- 28407491
TI - UV-C radiation increases sterol production in the microalga Pavlova lutheri.
AB - Plant sterols have become well-known to promote cardiovascular health through the
reduction of low density lipoprotein cholesterol in the blood. Plant sterols also
have anti-inflammatory, anti-cancer, anti-oxidative and anti-atherogenicity
activities. Microalgae have the potential to become a useful alternative source
of plant sterols with several species reported to have higher concentrations than
current commercial ones. In order to increase phytosterol production and optimise
culture conditions, the high sterol producer Pavlova lutheri was treated in
different dosages (50-250 mJ m-2) of UV-C radiation and several concentrations (1
500 MUmol/L) of hydrogen peroxide (H2O2) and the sterol contents were quantified
for two days after the treatments. The contents of malondialdehyde (MDA)
superoxide dismutase (SOD) as indications of cell membrane damage by lipid
peroxidation and repair of oxidative stress, respectively, were measured. Higher
activities of SOD and MDA were observed in the treated biomass when compared to
the controls. Total sterols increased in P. lutheri due to UV-C radiation (at 100
mJ m-2) but not in response to H2O2 treatment. Among the nineteen sterol
compounds identified in P. lutheri, poriferasterol, epicampesterol,
methylergostenol, fungisterol, dihydrochondrillasterol, and chondrillasterol
increased due to UV-C radiation. Therefore, UV-C radiation can be a useful tool
to boost industrial phytosterol production from P. lutheri.
PMID- 28407493
TI - Plasmonic titanium nitride nanoparticles for in vivo photoacoustic tomography
imaging and photothermal cancer therapy.
AB - Titanium nitride, an alternative plasmonic material to gold with unique
physiochemical properties, has been widely used in microelectronics, biomedical
devices and food-contact applications. However, its potential application in the
area of biomedicine has not been effectively explored. With the spectral match of
their plasmon resonance band and the biological transparency window as well as
good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising
photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging.
Nevertheless, the photothermal performance of TiN NPs has not been investigated
until now. Here, we presented the investigation of employing TiN NPs as
photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided
photothermal cancer therapy. Our experimental results showed that TiN NPs could
strongly absorb the NIR light and provided up to 48% photothermal conversion
efficiency. After PEGylation, the resultant nanoparticles demonstrated improved
physiological stability and extensive blood retention. Following intravenously
administration, they could simultaneously enhance the photoacoustic signals of
the tumor region and destroy tumors in the tumor-bearing mouse model by taking
advantage of the photothermal effect of the TiN NPs. Our findings highlighted the
great potential of plasmonic TiN NPs in detection and treatment of cancer.
PMID- 28407492
TI - Residual vein thrombosis and serial D-dimer for the long-term management of
patients with deep venous thrombosis.
AB - BACKGROUND: The optimal long-term strategy for preventing recurrent venous
thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain.
METHODS: In 620 consecutive outpatients with a first proximal DVT who had
completed at least three months of anticoagulation (unprovoked in 483, associated
with minor risk factors in 137), the ultrasound presence of residual vein
thrombosis (RVT) was assessed and defined as an incompressibility of at least
4mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was
stopped and D-dimer was repeated after one and three months. Anticoagulation was
resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. RESULTS:
During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of
the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1%
(95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to
4.5) in those with DVT associated with minor risk factors. Of the 233 males with
unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major
bleeding complications occurred in 8 patients while on anticoagulation, leading
to an annual rate of 1.2% (95% CI, 0.6 to 2.4). CONCLUSIONS: Discontinuing
anticoagulation in patients with a first episode of proximal DVT based on the
assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent
VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee
on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT
there is room for further improving the long-term strategy of VTE prevention.
(ClinicalTrials.gov number, NCT01285661).
PMID- 28407494
TI - Vaccine nanocarriers: Coupling intracellular pathways and cellular
biodistribution to control CD4 vs CD8 T cell responses.
AB - Nanoparticle delivery systems are known to enhance the immune response to soluble
antigens (Ags) and are thus a promising tool for the development of new vaccines.
Our laboratory has engineered two different nanoparticulate systems in which Ag
is either encapsulated within the core of polymersomes (PSs) or decorated onto
the surface of nanoparticles (NPs). Previous studies showed that PSs are better
at enhancing CD4 T cells and antibody titers, while NPs preferentially augment
cytotoxic CD8 T cells. Herein, we demonstrate that the differential activation of
T cell immunity reflects differences in the modes of intracellular trafficking
and distinct biodistribution of the Ag in lymphoid organs, which are both driven
by the properties of each nanocarrier. Furthermore, we found that Ags within PSs
promoted better CD4 T cell activation and induced a higher frequency of CD4 T
follicular helper (Tfh) cells. These differences correlated with changes in the
frequency of germinal center B cells and plasma cell formation, which reflects
the previously observed antibody titers. Our results show that PSs are a
promising vector for the delivery of Ags for B cell vaccine development. This
study demonstrates that nanocarrier design has a large impact on the quality of
the induced adaptive immune response.
PMID- 28407496
TI - Study of the wall effect of the sample position well of the Frisch-grid
ionization chamber.
AB - When measuring the charged particles using a Frisch-grid ionization chamber, the
sample is usually placed at the bottom of a sample position well on the common
cathode. Thus, there will be the wall effect of the sample position well and this
will change the measured energy spectrum of the charged particles. The wall
effect of the sample position well is proved to be noticeable by the present work
using experiments and simulations.
PMID- 28407495
TI - Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an
orthotopic rat model.
AB - Interest in non-invasive injectable therapies has rapidly risen due to their
excellent safety profile and ease of use in clinical settings. Injectable
hydrogels can be derived from the extracellular matrix (ECM) of specific tissues
to provide a biomimetic environment for cell delivery and enable seamless
regeneration of tissue defects. We investigated the in situ delivery of human
mesenchymal stem cells (hMSCs) in decellularized meniscus ECM hydrogel to a
meniscal defect in a nude rat model. First, decellularized meniscus ECM hydrogel
retained tissue-specific proteoglycans and collagens, and significantly
upregulated expression of fibrochondrogenic markers by hMSCs versus collagen
hydrogel alone in vitro. The meniscus ECM hydrogel in turn supported delivery of
hMSCs for integrative repair of a full-thickness defect model in meniscal
explants after in vitro culture and in vivo subcutaneous implantation. When
applied to an orthotopic model of meniscal injury in nude rat, hMSCs in meniscus
ECM hydrogel were retained out to eight weeks post-injection, contributing to
tissue regeneration and protection from joint space narrowing, pathologic
mineralization, and osteoarthritis development, as evidenced by macroscopic and
microscopic image analysis. Based on these findings, we propose the use of tissue
specific meniscus ECM-derived hydrogel for the delivery of therapeutic hMSCs to
treat meniscal injury.
PMID- 28407497
TI - Temperature effects on gallium arsenide 63Ni betavoltaic cell.
AB - A GaAs 63Ni radioisotope betavoltaic cell is reported over the temperature range
70 degrees C to -20 degrees C. The temperature effects on the key cell parameters
were investigated. The saturation current decreased with decreased temperature;
whilst the open circuit voltage, the short circuit current, the maximum power and
the internal conversion efficiency values decreased with increased temperature. A
maximum output power and an internal conversion efficiency of 1.8pW
(corresponding to 0.3MUW/Ci) and 7% were observed at -20 degrees C, respectively.
PMID- 28407498
TI - Partial replacement of animal fat by oleogels structured with monoglycerides and
phytosterols in frankfurter sausages.
AB - Sunflower oil was structured with monoglycerides and phytosterols. The properties
of the oleogels were studied by optical microscopy, large deformation mechanical
measurements, dynamic rheometry and differential scanning calorimetry. The
interaction between monoglycerides and phytosterols resulted in stronger oleogel
networks with a differentiated crystalline structure, increased hardness and gel
strength, increased storage modulus (G') values and decreased melting
temperatures compared to monoglycerides oleogels. The oleogel structured with
15:5 monoglycerides to phytosterols weight ratio was selected to replace 50% of
the pork backfat in frankfurter sausages. The control treatment (FSS1) presented
higher values of hardness, brittleness, gumminess and chewiness than the oleogel
substituted samples (FSS2), whereas cohesiveness and elasticity did not present
any differences. Instrumental color measurements indicated that FSS1 samples had
higher a*, lower L* and similar b* values compared to FSS2. No differences were
detected in the oxidation levels and sensory evaluation revealed similar overall
liking for the two treatments.
PMID- 28407499
TI - Alleviation of heavy metal toxicity and phytostimulation of Brassica campestris
L. by endophytic Mucor sp. MHR-7.
AB - Heavy metal (HM) pollution is of great concern in countries like Pakistan where a
huge proportion of human population is exposed to it. These toxic metals are
making their way from water bodies to soil where it not only interferes with
plant growth and development but also initiates serious health issues in human
consuming the produce of such soils. Bioremediation is one of the most viable and
efficient solution for the problem. Purpose of the current study was to isolate
endophytic fungi from plants grown on HM contaminated soil and screen them for
their ability to tolerate multiple HM including chromium (Cr6+), manganese
(Mn2+), cobalt (Co2+), copper (Cu2+) and zinc (Zn2+). Out of 27 isolated
endophytes, only one strain (MHR-7) was selected for multiple heavy metals
tolerance. The strain was identified as Mucor sp. by 18S and 28S ribosomal RNA
internal transcribed spacer (ITS) 1 and 4 sequence homology. The strain
effectively tolerated up to 900ugmL-1 of these heavy metals showing no remarkable
effect on its growth. The adverse effect of the heavy metals, measured as
reduction of the fungal growth increased with increasing concentration of the
metals. The strain was able to remove 60-87% of heavy metals from broth culture
when supplied with 300ugmL-1 of these metals. A trend of decline in
bioremediation potential of the strain was observed with increasing amount of
metals. The strain removed metals by biotransformation and/or accumulation of
heavy metal in its hyphae. Application of Mucor sp. MHR-7 locked down HM in tis
mycelium thereby making them less available to plant root reducing HM uptake and
toxicity in mustard. Besides its bioremediation potential, the strain was also
able to produce IAA, ACC deaminase and solubilize phosphate making it excellent
phytostimulant fungus. It is concluded that MHR-7 is an excellent candidate for
use as biofertilizer in fields affected with heavy metals.
PMID- 28407500
TI - In vitro and in vivo estrogenic activity of BPA, BPF and BPS in zebrafish
specific assays.
AB - Bisphenol A (BPA) is a widely used chemical that has been extensively studied as
an endocrine-disrupting chemical (EDC). Other bisphenols sharing close structural
features with BPA, are increasingly being used as alternatives, increasing the
need to assess associated hazards to the endocrine system. In the present study,
the estrogenic activity of BPA, bisphenol S (BPS) and bisphenol F (BPF) was
assessed by using a combination of zebrafish-specific mechanism-based in vitro
and in vivo assays. The three bisphenols were found to efficiently transactivate
all zebrafish estrogen receptor (zfER) subtypes in zebrafish hepatic reporter
cell lines (ZELH-zfERs). BPA was selective for zfERalpha while BPS and BPF were
slightly more potent on zfERbeta subtypes. We further documented the estrogenic
effect in vivo by quantifying the expression of brain aromatase using a
transgenic cyp19a1b-GFP zebrafish embryo assay. All three bisphenols induced GFP
in a concentration-dependent manner. BPS only partially induced brain aromatase
at the highest tested concentrations (>30uM) while BPA and BPF strongly induced
GFP, in an ER-dependent manner, at 1-10uM. Furthermore, we show that BPF strongly
induced vitellogenin synthesis in adult male zebrafish. Overall, this study
demonstrates the estrogenic activity of BPA, BPF and BPS in different cell- and
tissue-contexts and at different stages of development. Differences between in
vitro and in vivo responses are discussed in light of selective ER activation and
the fate of the compounds in the models. This study confirms the relevance of
combining cellular and whole-organism bioassays in a unique model species for the
hazard assessment of candidate EDCs.
PMID- 28407501
TI - Transcriptional changes in innate immunity genes in head kidneys from Aeromonas
salmonicida-challenged rainbow trout fed a mixture of polycyclic aromatic
hydrocarbons.
AB - We previously observed that exposure to a complex mixture of high molecular
weight polycyclic aromatic hydrocarbons (PAHs) increased sensitivity of rainbow
trout (Oncorhynchus mykiss) to subsequent challenge with Aeromonas salmonicida,
the causative agent of furunculosis. In this study, we evaluate potential
mechanisms associated with disease susceptibility from combined environmental
factors of dietary PAH exposure and pathogen challenge. Rainbow trout were fed a
mixture of ten high molecular weight PAHs at an environmentally relevant
concentration (7.82MUg PAH mixture/g fish/day) or control diet for 50 days. After
50 days of PAH exposure, fish were challenged with either Aeromonas salmonicida
at a lethal concentration 30 (LC30) or growth media without the pathogen (mock
challenge). Head kidneys were collected 2, 4, 10 and 20 days after challenge and
gene expression (q<0.05) was evaluated among treatments. In animals fed the PAH
contaminated diet, we observed down-regulation of expression for innate immune
system genes in pathways (p<0.05) for the terminal steps of the complement
cascade (complement component C6) and other bacteriolytic processes (lysozyme
type II) potentially underlying increased disease susceptibility after pathogen
challenge. Increased expression of genes associated with hemorrhage/tissue
remodeling/inflammation pathways (p<0.05) was likely related to more severe head
kidney damage due to infection in PAH-fed compared to control-fed fish. This
study is the first to evaluate transcriptional signatures associated with the
impact of chronic exposure to an environmentally relevant mixture of PAHs in
disease susceptibility and immunity.
PMID- 28407502
TI - Connections are not enough for membership: Letter/non-letter distinction persists
through phonological association learning.
AB - In compound, hierarchical stimuli (also known as Navon figures), a Global
Precedence Effect (GPE) can reliably be observed for both letters and non
letters. However, when presentation conditions sufficiently resemble those of
reading, the GPE for letters has occasionally been found to disappear. We
corroborate this effect in a study with a large group of participants. In
addition, in-between two sessions, participants were trained in associating the
non-letters with either phonological or non-phonological sounds. We reasoned that
learning distinctive phonological associations might be akin to the acquisition
of letter knowledge. This might eliminate the GPE also for the non-letters.
However, the GPE persisted for the trained non-letters in both conditions. The
large number of participants in this study revealed additional effects in the
letter condition, which enabled further insights in the processing dissociation
between letters and non-letter shapes.
PMID- 28407503
TI - Parkinsonian signs are a risk factor for falls.
AB - BACKGROUND: Parkinsonian signs are common, non-specific findings in older adults
and associated with increased rates of dementia and mortality. It is important to
understand which motor outcomes are associated with parkinsonian signs.
OBJECTIVES: To determine the role of parkinsonian signs on fall rates among older
adults. METHODS: We conducted a longitudinal study of primary care patients from
the University of Pennsylvania Health System. Adults over 55 years were assessed
at baseline through surveys and a neurological examination. We recorded falls
over the following 2 years. Parkinsonian signs were defined as the presence of 2
of 4 cardinal signs. Incident falls were compared between subjects with and
without parkinsonian signs, and modified Poisson regression used to adjust for
potential confounders in the relationship between parkinsonian signs and falls.
RESULTS: 982 subjects with a mean age of 68 (s.d. 8.8) years participated. 29% of
participants fell and 12% exhibited parkinsonian signs at baseline. The
unadjusted RR for falls among individuals with parkinsonian signs was 1.36 (95%
CI 1.05-1.76, p=0.02). After adjusting for age, cognitive function, urinary
incontinence, depression, diabetes, stroke and arthritis, individuals with
parkinsonian signs were still 38% more likely to fall than those without
parkinsonian signs (RR 1.38, 95% CI 1.04-1.82; p=0.03). Falls among those with
parkinsonian signs were more likely to lead to injury (53% vs 37%; p=0.04).
CONCLUSIONS: Parkinsonian signs are a significant, independent risk factor for
falls. Early detection of this clinical state is important in order to implement
fall prevention programs among primary care patients.
PMID- 28407504
TI - High-heeled walking decreases lumbar lordosis.
AB - An estimated 78% of women regularly walk in high heels. However, up to 58%
complain about low back pain, which is commonly thought to be caused by increased
lumbar lordosis. However, the extent to which a subject's posture is modified by
high-heeled shoes during dynamic activities remains unknown. Therefore, we sought
to evaluate whether low- or high-heeled shoes influence the kinematics of the
pelvis and the spine during walking. Twenty-three inexperienced women, and
seventeen women experienced in wearing high-heeled shoes, all aged 20-55 years,
were measured barefoot and while wearing low- (4cm) and high-heeled (10cm) shoes
during gait at a self-selected speed. A 22-camera motion capture system was used
to assess the gait patterns for each condition. No significant inter-experience
group kinematic differences were found. In contrast to the results of some
studies, our results show that the heels' height does indeed influence the motion
of the pelvis and the spine during walking, whereby low-heeled shoes influenced
the subjects' trunk kinematics during gait less than high-heeled shoes compared
to barefooted walking. However, inexperienced high-heel wearers showed less
thoracic curvature angle while wearing high-heels than while wearing low-heels.
Importantly, both groups exhibited significantly lower maximum and minimal lumbar
and thoracic curvature angles when wearing high-heeled shoes compared to the
barefoot condition. As a result, it seems that low back pain might be associated
with other factors induced by high-heels.
PMID- 28407505
TI - A randomized controlled trial on providing ankle-foot orthoses in patients with
(sub-)acute stroke: Short-term kinematic and spatiotemporal effects and effects
of timing.
AB - : Initial walking function is often limited after stroke, and regaining walking
ability is an important goal in rehabilitation. Various compensatory movement
strategies to ensure sufficient foot-clearance are reported. Ankle-foot orthoses
(AFOs) are often prescribed to improve foot-clearance and may influence these
strategies. However, research studying effects of actual AFO-provision early
after stroke is limited. We conducted an explorative randomized controlled trial
and aimed to study the short-term effects of AFO-provision on kinematic and
spatiotemporal parameters in patients early after stroke. In addition, we studied
whether timing of AFO-provision influenced these effects. Unilateral hemiparetic
patients maximal six weeks post-stroke were randomly assigned to AFO-provision:
early (at inclusion) or delayed (eight weeks later). Three-dimensional gait
analysis with and without AFO in randomized order was performed within two weeks
after AFO-provision. Twenty subjects (8 early, 12 delayed) were analyzed. We
found significant positive effects of AFO-provision for ankle dorsiflexion at
initial contact, foot-off and during swing (-3.6 degrees (7.3) vs 3.0 degrees
(3.9); 0.0 degrees (7.4) vs 5.2 degrees (3.7); and -6.1 degrees (7.8) vs 2.6
degrees (3.5), respectively), all p<0.001. No changes in knee, hip and pelvis
angles were found after AFO-provision, except for knee (+2.3 degrees ) and hip
flexion (+1.6 degrees ) at initial contact, p<=0.001. Significant effects of AFO
provision were found for cadence (+2.1 steps/min, p=0.026), stride duration (
0.08s, p=0.015) and single support duration (+1.0%, p=0.002). Early or delayed
AFO-provision after stroke did not affect results. In conclusion, positive short
term effects of AFO-provision were found on ankle kinematics early after stroke.
Timing of AFO-provision did not influence the results. TRIAL REGISTRATION NUMBER:
NTR1930.
PMID- 28407506
TI - Letter to the editor on "Textured and stimulating insoles for balance and gait
impairments in patients with multiple sclerosis and Parkinson's disease: A
systematic review and meta-analysis" by Martin Alfuth, Gait & Posture (2017) 51,
132-141.
PMID- 28407508
TI - Stress-related telomere length in children: A systematic review.
AB - Telomeres are repetitive DNA sequences at the ends of chromatids that shorten
following each cell replication. Once telomeres reach a critical length, DNA
defense mechanisms can direct cells to either a state of arrest (senescence) or
apoptosis. Stress induced by adversity is a probable cause of accelerated
telomere shortening from an early age. However, few studies have examined the
association between stress and telomere length in children, and it remains
unclear whether young individuals may show signs of cellular aging early in life.
Our aim was to examine whether adversity in childhood is associated with
shortening of telomere length. We conducted a systematic review of studies that
investigated the association between stress and telomere length in children from
3 to 15 years of age. Eleven studies met our selection criteria. We concluded
that adversity in childhood (such as violence, low socioeconomic status, maternal
depression, family disruption, and institutionalization) have an impact on
telomere length. This suggests that exposed individuals show signs of accelerated
erosion of telomeric ends from an early age. We discuss whether telomere
shortening is related to negative health outcomes later in life or could be a
biomarker predicting health outcomes. We believe that further large-scale
longitudinal studies that repeatedly monitor telomere length are very important
for providing a better assessment of telomere trajectory in psychologically
stressed children. This will verify the extent to which adversity impacts upon
the biological development of cell aging in childhood.
PMID- 28407507
TI - Concurrent validation of an index to estimate fall risk in community dwelling
seniors through a wireless sensor insole system: A pilot study.
AB - Falls are a major health problem for older adults with immediate effects, such as
fractures and head injuries, and longer term effects including fear of falling,
loss of independence, and disability. The goals of the WIISEL project were to
develop an unobtrusive, self-learning and wearable system aimed at assessing gait
impairments and fall risk of older adults in the home setting; assessing activity
and mobility in daily living conditions; identifying decline in mobility
performance and detecting falls in the home setting. The WIISEL system was based
on a pair of electronic insoles, able to transfer data to a commercially
available smartphone, which was used to wirelessly collect data in real time from
the insoles and transfer it to a backend computer server via mobile internet
connection and then onwards to a gait analysis tool. Risk of falls was calculated
by the system using a novel Fall Risk Index (FRI) based on multiple gait
parameters and gait pattern recognition. The system was tested by twenty-nine
older users and data collected by the insoles were compared with standardized
functional tests with a concurrent validity approach. The results showed that the
FRI captures the risk of falls with accuracy that is similar to that of
conventional performance-based tests of fall risk. These preliminary findings
support the idea that theWIISEL system can be a useful research tool and may have
clinical utility for long-term monitoring of fall risk at home and in the
community setting.
PMID- 28407509
TI - Infant word segmentation recruits the cerebral network of phonological short-term
memory.
AB - Segmenting word units from running speech is a fundamental skill infants must
develop in order to acquire language. Despite ample behavioral evidence of this
skill, its neurocognitive basis remains unclear. Using behavioral testing and
functional near-infrared spectroscopy, we aimed to uncover the neurocognitive
substrates of word segmentation and its development. Of three age-groups of
Japanese infants (5-6, 7-8, and 9-10months of age), the two older age-groups
showed significantly larger temporo-parietal (particularly supramarginal gyrus)
responses to target words repeatedly presented for training, than to control
words. After the training, they also exhibited stronger inferior frontal
responses to target words embedded in sentences. These findings suggest that word
segmentation largely involves a cerebral circuit of phonological (phonetic) short
term memory. The dorsal pathway involved in encoding and decoding phonological
representation may start to function stably at around 7months of age to
facilitate the growth of the infant's vocabulary.
PMID- 28407510
TI - Implicit co-activation of American Sign Language in deaf readers: An ERP study.
AB - In an implicit phonological priming paradigm, deaf bimodal bilinguals made
semantic relatedness decisions for pairs of English words. Half of the
semantically unrelated pairs had phonologically related translations in American
Sign Language (ASL). As in previous studies with unimodal bilinguals, targets in
pairs with phonologically related translations elicited smaller negativities than
targets in pairs with phonologically unrelated translations within the N400
window. This suggests that the same lexicosemantic mechanism underlies implicit
co-activation of a non-target language, irrespective of language modality. In
contrast to unimodal bilingual studies that find no behavioral effects, we
observed phonological interference, indicating that bimodal bilinguals may not
suppress the non-target language as robustly. Further, there was a subset of
bilinguals who were aware of the ASL manipulation (determined by debrief), and
they exhibited an effect of ASL phonology in a later time window (700-900ms).
Overall, these results indicate modality-independent language co-activation that
persists longer for bimodal bilinguals.
PMID- 28407511
TI - Clinical and cross-sectional imaging features of spontaneous pancreatic
pseudocyst-portal vein fistula.
AB - PURPOSE: To evaluate clinical and imaging features of pancreatic pseudocyst
portal vein fistula (PPVF). METHODS: Patients with evidence of PPVF on CT/MRI
were included. Clinical presentation, outcomes, imaging appearance of the portal
vein were recorded. RESULTS: 75% of patients developed portal hypertension, 62%
cavernous transformation of the portal vein and 25% portal biliopathy. PPVF
presented on CT as fluid-attenuated portal vein, and on MRI as T2-weighted
hyperintense fluid-filled portal vein. PPVF was misdiagnosed as portal vein
thrombosis in all patients who underwent CT as initial examination. CONCLUSIONS:
Whenever PPVF is suspected on CT, MRI can be helpful to achieve accurate
diagnosis and avoid unnecessary interventions.
PMID- 28407512
TI - Impact of large ovarian endometriomas on the response to superovulation for in
vitro fertilization: A retrospective study.
AB - OBJECTIVE: To assess the response to superovulation for in vitro fertilization
(IVF) in patients with unilateral endometriomas with diameter >=5cm and in the
contralateral healthy ovary. STUDY DESIGN: This retrospective analysis of a
prospectively collected database included patients who underwent superovulation
for IVF/ICSI cycles and had unoperated single unilateral endometrioma with
diameter >=5cm and healthy contralateral ovary. The primary outcome of the study
was to compare the number of oocyte retrieved in the ovary with the endometrioma
and the contralateral healthy ovary. RESULTS: The total number of follicles was
lower in ovaries with endometriomas (2.6+/-1.3) than in healthy ovaries (4.8+/
2.0; p<0.001). The number of codominant follicles and the total number of oocytes
retrieved were lower in ovaries with endometriomas (1.5+/-0.9 and 2.0+/-1.2) than
in the contralateral ovaries (3.7+/-1.5 and 4.2+/-1.7; p<0.001, respectively).
The number of oocytes retrieved suitable for fertilization was lower in ovaries
with endometriomas (1.5+/-1.1) than in the healthy ovaries (3.3+/-1.5; p<0.001).
The total number of oocytes retrieved and the number of oocytes retrieved
suitable for fertilization were lower in ovaries with endometriomas respectively
in 21 (80.8%) and in 20 (76.9%) cases. The decreased responsiveness to ovarian
superovulation was confirmed considering women with ultrasonographic diagnosis of
deep infiltrating endometriosis. 30.8% of patients had positive HCG; the
pregnancy rate was 23.1%. CONCLUSION: The presence of large endometriomas (>=5cm)
at time of IVF significantly decreases the number of oocyte retrieved compared
with the contralateral healthy ovaries.
PMID- 28407513
TI - Effects of cyanobacteria Synechocystis spp. in the host-parasite model
Crassostrea gasar-Perkinsus marinus.
AB - Perkinsosis is a disease caused by protozoan parasites from the Perkinsus genus.
In Brazil, two species, P. beihaiensis and P. marinus, are frequently found
infecting native oysters (Crassostrea gasar and C. rhizophorae) from cultured and
wild populations in several states of the Northeast region. The impacts of this
disease in bivalves from Brazil, as well as the interactions with environmental
factors, are poorly studied. In the present work, we evaluated the in vitro
effects of the cyanobacteria Synechocystis spp. on trophozoites of P. marinus and
haemocytes of C. gasar. Four cyanobacteria strains isolated from the Northeast
Brazilian coast were used as whole cultures (WCs) and extracellular products
(ECPs). Trophozoites of P. marinus were exposed for short (4h) and long (48h and
7days, the latter only for ECPs) periods, while haemocytes were exposed for a
short period (4h). Cellular and immune parameters, i.e. cell viability, cell
count, reactive oxygen species production (ROS) and phagocytosis of inert (latex
beads) and biological particles (zymosan and trophozoites of P. marinus) were
measured by flow cytometry. The viability of P. marinus trophozoites was improved
in response to WCs of Synechocystis spp., which could be a beneficial effect of
the cyanobacteria providing nutrients and reducing reactive oxygen species. Long
term exposure of trophozoites to ECPs of cyanobacteria did not modify in vitro
cell proliferation nor viability. In contrast, C. gasar haemocytes showed a
reduction in cell viability when exposed to WCs, but not to ECPs. However, ROS
production was not altered. Haemocyte ability to engulf latex particles was
reduced when exposed mainly to ECPs of cyanobacteria; while neither the WCs nor
the ECPs modified phagocytosis of the biological particles, zymosan and P.
marinus. Our results suggest a negative effect of cyanobacteria from the
Synechocystis genus on host immune cells, in contrast to a more beneficial effect
on the parasite cell, which could together disrupt the balance of the host
parasite interaction and make oysters more susceptible to P. marinus as well as
opportunistic infections.
PMID- 28407514
TI - Age estimation from structural changes of teeth and buccal alveolar bone level.
AB - Forensic odontology plays a vital role in the identification and age estimation
of unknown deceased individuals. The purpose of this study is to estimate the
chronological age from Cone-Beam Computed Tomography (CBCT) images by measuring
the buccal alveolar bone level (ABL) to the cemento-enamel junction and to
investigate the possibility of employing the age-related structural changes of
teeth as studied by Gustafson. In addition, this study will determine the
forensic reliability of employing CBCT images as a technique for dental age
estimation. A total of 284 CBCT images of Malays and Chinese patients (150
females and 134 males), aged from 20 years and above were selected, measured and
stages of age-related changes were recorded using the i-CAT Vision software.
Lower first premolars of both left and right side of the jaw were chosen and the
characteristics described by Gustafson, namely attrition, secondary dentine
formation and periodontal recession were evaluated. Linear regression analysis
was performed for the buccal bone level and the R values obtained were 0.85 and
0.82 for left and right side respectively. Gustafson's characteristics were
analysed using multiple regression analysis with chronological age as the
dependent variable. The results of the analysis showed R values ranged from 0.44
to 0.62. Therefore it can be safely concluded that the buccal bone level highly
correlated with the chronological age and is consequently the most suitable age
related characteristic for forensic age estimation.
PMID- 28407515
TI - High CD200 expression is associated with poor prognosis in cytogenetically normal
acute myeloid leukemia, even in FlT3-ITD-/NPM1+ patients.
AB - Overexpression of CD200, a trans-membrane protein belonging to the immunoglobulin
superfamily, has been associated with poor prognosis in patients with acute
myeloid leukemia (AML). As few data are available in the subset of
cytogenetically-normal (CN) AML, we retrospectively evaluated the correlations
between CD200 expression and response to therapy in a series of 139 adults with
CN-AML. CD200 was expressed in 67/139 (48%) cases; 18 of them (28%) expressed
CD200 at high intensity. No differences in CD200 expression rate were observed
according to age, WBC count, type of leukemia, FLT3 or NMP1 mutation, and CD56
expression. A higher incidence of CD200 expression was observed in CD34+ cases
(P<0.0001) and in BCL2+ patients (P=0.04). Complete remission (CR) was evaluable
achieved in 98 patients (70%): 56/71 (79%) in CD200- and 47/67 (63%) in CD200+
patients (P=0.03), with a lower CR rate in patients with high CD200 intensity
(9/18, 50%). CD200 expression had a negative impact on long-term outcome. CD200
expression, per se, did not impact on disease-free survival (DFS), but cases with
high CD200 expression had a lower 3-year DFS compared to CD200-negative and low
expressing ones (0% vs 65% vs 68%, P=0.019). Three-year overall survival (OS) was
51% in CD200- and 27% in CD200+ patients (P=0.01), with a significant difference
among cases with low or high CD200 expression (35% vs 0%, P=0.001). CD200 high
expression defined a group with very poor DFS and OS also among the 37 FLT3
/NPM1+: 3-year DFS and OS were 88% and 60% in CD200-, 50% and 32% in CD200 low
and 0% and 0% in CD200 high patients, respectively (P=0.01 for DFS and P=0.05 for
OS). Our data suggest a negative impact of CD200 expression in CN-AML, with a
further worsening in high-expressing cases, also in the subset of FLT3-/NPM1+
patients.
PMID- 28407516
TI - Quantitative miR analysis in chronic lymphocytic leukaemia/small lymphocytic
lymphoma - proliferation centres are characterized by high miR-92a and miR-155
and low miR-150 expression.
AB - Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic
lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal
abnormalities have already been described to accumulate preferably in the PCs as
opposed to the intervening small cell areas. To further characterize the
pathogenic role of PCs, the expression levels of 17 selected miRs known to be
involved in the development of CLL/SLL were compared in the PCs and the
intervening small cell areas in lymph nodes of 15 patients with CLL/SLL. The miR
expression levels were also compared to the cytogenetic alterations defined by
FISH analysis. Our results show that two known oncomiRs, miR-155 and -92a were
upregulated and the tumour suppressor miR-150 was downregulated in the PCs. Low
expression of miR-150 was also associated with loss of 11q. In summary we found
significantly higher expression of oncomiRs and lower expression of a tumour
suppressor miR in PCs of CLL/SLL lymph nodes, which support the hypothesis that
the PCs may drive the disease and play a role in progression.
PMID- 28407517
TI - Social status strategy in early adolescent girls: Testosterone and value-based
decision making.
AB - There has been strong interest, spanning several disciplines, in understanding
adolescence as a developmental period of increased risk-taking behavior. Our
goals focus on one line of investigation within this larger developmental risk
framework. Specifically, we examined levels of pubertal hormones in girls in
relation to their willingness to take greater financial risks to gain social
status. To this end, we tested the hypothesis that higher levels of testosterone
during the ages of pubertal maturation are associated with a greater willingness
to sacrifice money for social admiration. Sixty-three girls ages 10-14
(Mage=12.74) participated in laboratory measures and completed at-home saliva
sample collection. The Pubertal Development Scale (PDS) and basal hormone levels
(testosterone, estradiol, DHEA) measured pubertal maturation. We made use of a
developmentally appropriate version of an Auction Task in which adolescents could
take financial risks in order to gain socially motivated outcomes (social
status). PDS and testosterone were each associated with overall levels of
financial risk taking over the course of the Auction Task. In hierarchical
models, PDS and testosterone were predictors of the slope of overbidding over the
course of the task. Results provide evidence for the role of testosterone and
pubertal maturation in girls' motivations to engage in costly decision making in
order to gain social status. Findings contribute to our understanding of the
developmental underpinnings of some interesting aspects of adolescent risk
behavior.
PMID- 28407518
TI - Evaluating executive function in patients with temporal lobe epilepsy using the
frontal assessment battery.
AB - Previous studies have demonstrated executive dysfunction in patients with
temporal lobe epilepsy (TLE). Frontal assessment battery (FAB) is a short
neuropsychological tool that was developed for assessment of frontal lobe
function in a clinical setting. The aim of the present study is to evaluate the
clinical utility of FAB for detection of executive dysfunction in TLE patients.
Forty-eight TLE patients and 48 sex and age-matched healthy controls participated
in this study. Compared to healthy participants, the total FAB score was
significantly lower among the TLE patients. TLE patients performed significantly
worse at the mental flexibility, motor programming, sensitivity to interference
and inhibitory control tasks. The duration of time has been passed since the last
seizure was the only significant predictor of FAB score and patients who had a
seizure less than a week before the evaluation time, had significantly lower FAB
scores. The number of antiepileptic drugs (AEDs) did not influence the executive
function in this study; however, sodium valproate was found to affect the mental
flexibility. In conclusion, impaired executive function is common in TLE
patients, and we suggest that FAB is a clinically applicable tool to monitor it.
Moreover, we found that the time of the last seizure is a significant predictor
of executive functioning and patients' performance may become worse up to seven
days after a seizure. We also recommend that clinicians evaluate the cognitive
adverse effects of AEDs especially sodium valproate, which was found to affect
the mental flexibility in this study.
PMID- 28407519
TI - Skeletal muscle autophagy and its role in sarcopenia and organismal aging.
AB - Sarcopenia, the loss of skeletal muscle mass and strength in the aged, is an
important medical condition but its etiology is incompletely understood. Because
autophagy promotes myofiber atrophy in the young, it was believed that autophagy
inhibition would prevent sarcopenia. However, recent studies have revealed that
autophagy actually maintains muscle mass and that its function declines during
muscle aging. Consistently, boosting basal autophagy protects from age-related
muscle dysfunction by promoting the selective degradation of misfolded proteins
and dysfunctional organelles. Conversely, autophagy inhibition leads to loss of
muscle strength and induces a maladaptive stress response responsible for
myofiber atrophy in the aged. In addition to cell-autonomous effects, muscle
autophagy and associated signaling pathways induce systemic responses in other
aging tissues by modulating the expression and secretion of myokines. We propose
that myokines and pharmacologic interventions that boost selective autophagy may
prevent sarcopenia, delay systemic aging, and extend health span.
PMID- 28407520
TI - Anticholinergic drug use is associated with episodic memory decline in older
adults without dementia.
AB - Anticholinergic drug use is common in older adults and has been related to
increased dementia risk. This suggests that users of these drugs may experience
accelerated cognitive decline. So far, however, longitudinal data on this topic
are absent and the available evidence is inconclusive with respect to effects on
specific cognitive domains due to suboptimal control of confounding variables. We
investigated whether anticholinergic medication use is associated with cognitive
decline over 6 years in a population-based study of older adults (aged 60-90; n =
1473) without dementia. We found that users (n = 29) declined more on episodic
memory over 6 years compared to nonusers (n = 1418). These results were
independent of age, sex, education, overall drug intake, physical activity,
depression, cardiovascular risk burden, and cardiovascular disease. By contrast,
anticholinergic drug use was unrelated to performance in processing speed,
semantic memory, short-term memory, verbal fluency, and global cognition (the
Mini-Mental-State Examination). Our results suggest that effects of
anticholinergics may be particularly detrimental to episodic memory in older
adults, which supports the assertion that the cholinergic system plays an
important role in episodic memory formation.
PMID- 28407521
TI - Genetic or pharmacological activation of the Drosophila PGC-1alpha ortholog
spargel rescues the disease phenotypes of genetic models of Parkinson's disease.
AB - Despite intensive research, the etiology of Parkinson's disease (PD) remains
poorly understood and the disease remains incurable. However, compelling evidence
gathered over decades of research strongly support a role for mitochondrial
dysfunction in PD pathogenesis. Related to this, PGC-1alpha, a key regulator of
mitochondrial biogenesis, has recently been proposed to be an attractive target
for intervention in PD. Here, we showed that silencing of expression of the
Drosophila PGC-1alpha ortholog spargel results in PD-related phenotypes in flies
and also seem to negate the effects of AMPK activation, which we have previously
demonstrated to be neuroprotective, that is, AMPK-mediated neuroprotection
appears to require PGC-1alpha. Importantly, we further showed that genetic or
pharmacological activation of the Drosophila PGC-1alpha ortholog spargel is
sufficient to rescue the disease phenotypes of Parkin and LRRK2 genetic fly
models of PD, thus supporting the proposed use of PGC-1alpha-related strategies
for neuroprotection in PD.
PMID- 28407522
TI - Physiological arousal accompanying postural responses to external perturbations
after stroke.
AB - OBJECTIVE: The purpose of this study was to examine simultaneously the level of
physiological arousal and the postural response to external perturbations in
people post-stroke compared to age-matched controls to build a more comprehensive
understanding of the effect of stroke on postural control and balance self
efficacy. METHODS: Participants stood with each foot on separate force platforms.
Ten applications of loads of 2% body weight at the hips perturbed the participant
anteriorly under two conditions: investigator-triggered or self-triggered (total
20). Electrodermal activity (EDA; measurement of physiological arousal),
electromyography (EMG) of the ankle plantarflexor muscles and anterior-posterior
center of pressure measurements were taken pre-perturbation (anticipatory) and
post-perturbation (response) and compared between the initial (first two) and
final (last two) perturbations. RESULTS: Participants post-stroke demonstrated
significantly higher levels of anticipatory EDA and anticipatory paretic
plantarflexor EMG during both self- and investigator-triggered conditions
compared to controls. Anticipatory EDA levels were higher in the final
perturbations in participants post-stroke in both conditions, but not in
controls. Habituation of the EDA responses post-perturbation was exhibited in the
self-triggered perturbations in controls, but not in participants post-stroke.
CONCLUSIONS: Physiological arousal and postural control strategies of controls
revealed habituation in response to self-triggered perturbations, whereas this
was not seen in participants post-stroke. SIGNIFICANCE: Understanding the
physiological arousal response to challenges to standing balance post-stroke
furthers our understanding of postural control mechanisms post-stroke.
PMID- 28407523
TI - GLUT1-deficiency syndrome: Report of a four-generation Norwegian family with a
mild phenotype.
AB - INTRODUCTION: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare
metabolic encephalopathy with a wide variation of clinical phenotypes. Familial
variants are often milder than de novo cases, and may therefore remain
undiagnosed. The aim of this study was to characterize the clinical course of
GLUT1-DS in a four-generation Norwegian family where the oldest generations had
never received any treatment. METHOD: Through interviews and clinical
investigations, we characterized a family of 26 members, where 11 members had
symptoms strongly suggesting GLUT1-DS. All members were offered genetic testing
of the SLC2A1 gene. Affected members were offered treatment with ketogenic diet,
and the effect of the treatment was registered. RESULTS: We sequenced the SLC2A1
gene in 13 members, and found that 10, all with symptoms, had the c.823G>A
(p.Ala275Thr) variant. All affected members had experienced early-onset epilepsy,
paroxysmal exercise-induced dyskinesias, and most had mild learning disability.
Moreover, some had symptoms and signs of a distal neuropathy in addition to
reduced sense of orientation and excessive daytime sleep. Their load of symptoms
had decreased over the years, although that they never had received any
treatment. Nevertheless, those who started dietary treatment all experienced an
improved quality of life. CONCLUSION: We report a four-generation family with
GLUT1-DS where the disease has a mild course, even when untreated. In addition to
classical GLUT1-DS features, we also describe symptoms which have never been
reported in GLUT1-DS previously. As such, this family extends the phenotypic
spectrum of GLUT1-DS and underlines the importance of diagnosing also relatively
mildly affected patients, even in adult life, as they also seem to benefit from
dietary treatment.
PMID- 28407524
TI - Age at surgery as a predictor of cognitive improvements in patients with drug
resistant temporal epilepsy.
AB - Temporal lobe epilepsy (TLE) surgery is an effective procedure that can produce
cognitive changes. However, the prognostic factors related with cognitive
outcomes need to be better understood. The aim of the present study is to know if
age at surgery is a reliable predictor of verbal memory competence and
considering factors such as: hemisphere; type of surgery; pre-surgical seizure
frequency; and epilepsy duration. Sixty-one typically dominant patients with drug
resistant TLE (34 with left TLE [L-TLE] and 27 with right TLE [R-TLE]) underwent
a neuropsychological assessment before and a year after surgery. Results showed
that R-TLE patients had better evolution in short- and long-term verbal memory
and naming than L-TLE patients (for all, p >.04). L-TLE patients also more
frequently showed a strong and reliable decline in these functions than R-TLE
patients. No effects for gender or type of surgery were found. From a
multivariate approach, patients with improvements in verbal competence underwent
surgery at earlier ages and suffered epilepsy for less time (for all, p <0.4).
The relevance of age at surgery was confirmed as a predictor of long-term verbal
memory changes, although the frequency of partial seizures also explains, at
least partially, these changes. In addition, the frequency of partial seizures
explains short-term verbal memory changes. These results emphasize the importance
of early intervention, independently of the resected hemisphere, in order to
minimize the cognitive side-effects of epilepsy treatment, as well the need to
consider cognitive functions as related processes and network dependent.
PMID- 28407525
TI - Mind the gap: Exploring information gaps for the development of an online
resource hub for epilepsy and depression.
AB - PURPOSE: Depression is common in epilepsy, and is often under-detected and under
treated. The motivation to create a depression eHub for persons with epilepsy is
to connect them to the best available online resources to effectively manage
their depression. The study sought to: 1) identify facilitators and barriers to
accessing resources related to management of epilepsy and/or depression and 2)
discuss gaps in available resources (free and in the public domain) and 3)
identify suggestions for future content. METHODS: Semi-structured interviews were
conducted with ten patients with epilepsy and a history of depression. Using
inductive analysis, two team members engaged in a process of textual open-coding
utilizing a conventional content analysis approach whereby content was
conceptually clustered based on the research questions. A phenomenological
framework was applied to describe the phenomenon of online health resource access
and utilization from the perspective of people with epilepsy. RESULTS:
Facilitators to the use of online resources included information credibility,
thoughtful organization, and accessibility of resources. Barriers included
difficulties finding and piecing together information from many different sites.
Patients reported difficulty having the motivation to seek out resources while
depressed, which was compounded by feelings of stigma, social isolation, and lack
of control. Gaps in resources included a lack of information about living with
epilepsy day-to-day and resources for family and friends. Suggested content
included information to raise awareness about epilepsy and depression;
questionnaires to screen for symptoms of depression; stories of other patients
with epilepsy and depression via video or moderated forums; current research and
news; local community resources; and tools and strategies to manage depression in
epilepsy. CONCLUSIONS: There is a gap in accessible resources for patients with
epilepsy and depression as well as barriers that include epilepsy-related
restrictions, depression-related impairments, lack of awareness, and
stigmatization. These results should be used to guide the development of e-Health
resources for patients with epilepsy.
PMID- 28407526
TI - The impact of antidepressants on seizure frequency and depressive and anxiety
disorders of patients with epilepsy: Is it worth investigating?
AB - PURPOSE: Depression and anxiety disorders in patients with epilepsy (PWE) remain
under-recognized and under-treated, despite being the most common psychiatric co
morbidities. Selective serotonin re-uptake inhibitors (SSRIs) and serotonin
norepinephrine reuptake inhibitors (SNRIs) are considered first-line treatment
for primary depression and anxiety disorders. We performed this study to
investigate if SSRIs and SNRIs could affect the seizure frequency of PWE and to
assess whether such effect is independent of the response of the mood and anxiety
disorders to these drugs. METHODS: This was a retrospective study of 100
consecutive PWE who were started on an SSRI or SNRI for the treatment of a
depressive and/or anxiety disorder. Every patient underwent a psychiatric
evaluation by one of the investigators using a semi-structured interview who also
managed the pharmacologic treatment in all the patients. Patients were excluded
if they had a diagnosis of psychogenic non-epileptic seizures or if they had
undergone epilepsy surgery or the implant of the vagal nerve stimulator six
months before and after the start of the antidepressant therapy. The final
analysis was conducted in 84 patients. For each type of seizure, an average and
maximal monthly seizure frequency during the six months preceding and following
the start of psychotropic drugs was extracted from the medical records. We
identified the number of patients whose seizure frequency during treatment with
antidepressants: (i) shifted from a <1/month to a >=1 seizure/month and vice
versa, (ii) increased beyond maximal/monthly baseline frequency, and (iii)
patients who developed de-novo generalized tonic-clonic (GTC) seizures. RESULTS:
None of the patients with a baseline seizure frequency <1seizure/month went on to
have >=1seizure/month after initiating treatment with antidepressants, had an
increase in frequency beyond baseline maximal counts or developed de-novo-GTC
seizures. Furthermore, there was no seizure recurrence among patients that had
been seizure-free. Among the patients with a baseline seizure frequency
>=1/month, 27.5% had a reduction in seizure frequency to <1/month, which
suggested a positive effect of SSRI/SNRI on seizure frequency (p=0.001, McNemar
test). Among the patients with a baseline seizure frequency >=1seizure/month, 48%
exhibited a >50% reduction in seizure frequency after the start of treatment with
SSRIs or SNRIs. A therapeutic response to SSRIs and SNRIs was found in 73% of
patients. The change in seizure frequency was independent of the improvement in
psychiatric symptomatology. CONCLUSION: In this retrospective observational
study, SSRIs or SNRIs did not appear to worsen seizure frequency. Also, in
patients with frequent seizures, SSRIs and SNRIs may be associated with a
possible decrease in seizure frequency. Furthermore, these drugs appear to yield
good therapeutic response of psychiatric symptoms independently of seizure
frequency. It is pivotal to replicate these data in prospective, double-blind,
placebo-controlled trials.
PMID- 28407527
TI - Top-down control over feedback processing: The probability of valid feedback
affects feedback-related brain activity.
AB - Adaptive decision-making requires that feedback about decision outcomes is
adequately processed. Recent studies have shown that fronto-central event-related
potentials (ERPs) are sensitive to feedback valence and can be used as an index
of feedback processing. The present study investigated whether the processes
involved in feedback evaluation are affected by top-down mechanisms driven by
knowledge about feedback validity. In a simple decision task, participants had to
make use of feedback to learn which one of two stimuli was associated with a
reward in a later test phase. Feedback stimuli were followed by a cue indicating
whether feedback was valid or invalid. Prior to each block, participants were
informed about the frequency of valid feedback in this block. An effect of
feedback validity was obtained not only for learning but also for fronto-central
ERPs. While high-validity feedback was associated with a fronto-central valence
effect, this effect was absent for low-validity feedback. This indicates that
processes involved in feedback evaluation are affected by prior knowledge about
feedback validity via top-down processes.
PMID- 28407528
TI - Immunotherapy revolutionises non-small-cell lung cancer therapy: Results,
perspectives and new challenges.
AB - Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling
pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1
and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was
the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a
second-line treatment setting. Results from recent phase II and phase III
randomised trials testing other ICIs have been presented. In Keynote-024,
pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the
first-line treatment of PDL1 >= 50% tumours (30% of screened tumours), with a
progression-free survival (PFS, median) of 10.4 months versus 6.0 months with
chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37
0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT (P =
0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate
026 reported that nivolumab failed to show any benefit compared with standard
platinum-based CT, with a PFS (median) in the PDL1 >= 5% NSCLC group of 4.2
months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91-1.45, P = 0.25).
No benefit was observed in the PDL1 >= 50% subgroup. An encouraging report of the
efficacy of pembrolizumab in addition to CT in first-line treatment in unselected
NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT
alone (P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for
second-line treatment compared with docetaxel (OAK phase III study) with an OS
(median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a
new paradigm for the treatment of advanced NSCLC using pembrolizumab for the
first-line treatment of PDL1 >= 50% tumours.
PMID- 28407529
TI - Resection of colorectal liver metastases after second-line chemotherapy: is it
worthwhile? A LiverMetSurvey analysis of 6415 patients.
AB - PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM)
following second-line preoperative chemotherapy (PCT) performed for insufficient
response or toxicity of the first-line, is little known and has here been
compared to the outcome following first-line. PATIENTS AND METHODS: From January
2005 to June 2013, 5624 and 791 consecutive patients of a prospective
international cohort received 1 and 2 PCT lines before CLM resection (group 1 and
2, respectively). Survival and prognostic factors were analysed. RESULTS: After a
mean follow-up of 30.1 months, there was no difference in survival from CLM
diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49%
in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32).
After hepatectomy, disease-free survival (DFS) was however shorter in group 2:
17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P =
0.001). Among the initially unresectable patients of group 1 and 2, no
statistical difference in OS or DFS was observed. Independent predictors of worse
OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour
progression on second line, R2 resection and number of hepatectomies/year <50.
Positive primary nodes, synchronous and bilateral metastases were predictors of
shorter DFS. Initial unresectability did not impact OS or DFS in group 2.
CONCLUSION: CLM resection following second-line PCT, after oncosurgically
favourable selection, could bring similar OS compared to what observed after
first-line. For initially unresectable patients, OS or DFS is comparable between
first- and second-line PCT. Surgery should not be denied after the failure of
first-line chemotherapy.
PMID- 28407530
TI - Redox-responsive nanocarriers for drug and gene co-delivery based on chitosan
derivatives modified mesoporous silica nanoparticles.
AB - Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are
promising strategy in cancer therapy. The ultimate goal is to deliver high local
concentration of therapeutic agents with no premature release and result in
synergistic effects for combination therapies. In this work, we developed a redox
stimuli-responsive and synergistic co-delivery system for anticancer drug DOX and
p53 gene for potential cancer therapy. A dendronized chitosan derivative (CP) as
a "gatekeeper" to control release the drug was used to modify MSNs via a
disulfide linker and improve the gene transfection efficiency. Stimulus-induced
release of the DOX was studied in the presence of glutathione (GSH), which showed
that polymer shell was shed and accelerated the release of embedded drugs inside
the tumor cells under a GSH-rich environment. The obtained nanoparticles showed
good gene delivery ability in vitro by inducing an obvious increase in p53
protein expression in Hela cells. Apoptosis analysis confirmed that DOX and p53
could be co-delivered to the Hela cells by MSN-SS-CP nanocarriers and induced
significant cell apoptosis. These results demonstrated that the dual delivery
system resulted in synergistic effects and lead to an effective cancer cell
apoptosis, which may be promising for cancer therapeutic application.
PMID- 28407531
TI - Precise ratiometric loading of PTX and DOX based on redox-sensitive mixed
micelles for cancer therapy.
AB - PTX and DOX have different anticancer mechanisms. The combination of the two
anticancer drugs could synergically enhance their anticancer effect, but
simultaneously accompanied by severe side effects. In the present study, we
constructed a mixed micelle system based on redox-sensitive mPEG-SS-PTX and mPEG
SS-DOX conjugate. The drug delivery system has a fixed and high drug loading
content of 24.2% (PTX~14.8% and DOX~9.4%) with a precise ratio of PTX and DOX to
realize the synchronized and controlled release. The mixed micelle has an average
size of 93.3nm with a narrow distribution, suitable for passive targeting to
tumor tissues by the EPR effect. In vitro release profile and in vitro anticancer
results show the mixed micelles have obvious redox-sensitive release properties
in reducing environment and have a significant cytotoxicity to A549 and B16
cells. Importantly, in vivo study shows the mixed micelles have no obvious side
effect on mice compared to free PTX/DOX samples during the treatment. Therefore,
the constructed redox-sensitive mixed micelle is a promising drug delivery system
for cancer therapy.
PMID- 28407532
TI - Rational approach to solvent system selection for liquid-liquid extraction
assisted sample pretreatment in counter-current chromatography.
AB - A rational liquid-liquid extraction approach was established to pre-treat samples
for high-speed counter-current chromatography (HSCCC). n-Hexane-ethyl acetate
methanol-water (4:5:4:5, v/v) and (1:5:1:5, v/v) were selected as solvent systems
for liquid-liquid extraction by systematically screening K of target compounds to
remove low- and high-polarity impurities in the sample, respectively. After
liquid-liquid extraction was performed, 1.4g of crude sample II was obtained from
18.5g of crude sample I which was extracted from the flowers of Robinia
pseudoacacia L., and then separated with HSCCC by using a solvent system composed
of n-hexane-ethyl acetate-methanol-water (1:2:1:2, v/v). As a result, 31mg of
robinin and 37mg of kaempferol 7-O-alpha-l-rhamnopyranoside were isolated from
200mg of crude sample II in a single run of HSCCC. A scale-up separation was also
performed, and 160mg of robinin with 95% purity and 188mg of kaempferol 7-O-alpha
l-rhamnopyranoside with 97% purity were produced from 1.2g of crude sample II.
PMID- 28407533
TI - Determination of brusatol in plasma and tissues by LC-MS method and its
application to a pharmacokinetic and distribution study in mice.
AB - OBJECTIVES: The quassinoid brusatol, which can be isolated from Brucea javanica
(L.) Merr., becomes popularly studied because of its anti-tumor activity. In
order to further investigate brusatol and extend its applications, a sensitive
analytical method for determination of brusatol in biological samples is
essential. However, few methods had been reported until now. In this study, a
highly sensitive and reproducible LC-MS method for simultaneous quantification of
brusatol in mouse plasma and tissues was developed and validated. METHOD: Plasma
samples and tissue homogenate were extracted with diethyl ether after addition of
the internal standard solution(IS). The supernatant was blown to dryness with
nitrogen and residual was reconstituted with 100MUl of methanol. The separation
was performed on an Intersil ODS-3 column and gradient elution was conducted with
the mobile phase of water and methanol (0-5min 47:53, 5-5.5min 47:53-10:90, 5.5
9min 10:90, posttime 4min 47:53) at a flow rate of 0.8mL/min. Quantification was
performed in the selected ion monitoring (SIM) mode at m/z 543.2 for brusatol and
220.0 for IS (ornidazole). The method was validated by analyzing quality control
plasma and tissue homogenate samples, and was applied to analyze samples obtained
from mice after injections of brusatol via the tail vein. RESULTS: With
ornidazole as the internal standard, calibration curve of the method ranged from
10 to 320ng/ml for plasma and 10-240ng/ml for tissues. Recovery rate of brusatol
from plasma and tissues were between 71.09%-94.91%. Relative standard deviation
(RSD) for inter- and intra-day precision was less than 15%, and the accuracy was
between 96.1%-111.8%. The pharmacokinetics and distribution study of brusatol in
mice after three single doses via the tail vein were carried out based on this
method. The concentration of brusatol in plasma decreased rapidly and a more than
10 fold concentration of brusatol was found as compared to that in other tissues.
CONCLUSIONS: This is the first reported LC-MS method for detecting brusatol in
tissues and can accurately determine the concentrations of these compounds in
plasma and different tissues. Further research on the metabolism of brusatol in
vivo is still needed.
PMID- 28407534
TI - Yield of brain imaging of neurologically normal children with first afebrile
seizure in the outpatient clinical setting.
PMID- 28407535
TI - Exploring parental behavior and child interactive engagement: A study on children
with a significant cognitive and motor developmental delay.
AB - BACKGROUND AND AIMS: Parenting factors are one of the most striking gaps in the
current scientific literature on the development of young children with
significant cognitive and motor disabilities. We aim to explore the
characteristics of, and the association between, parental behavior and children's
interactive engagement within this target group. METHODS AND PROCEDURES: Twenty
five parent-child dyads (with children aged 6-59 months) were video-taped during
a 15-min unstructured play situation. Parents were also asked to complete the
Parental Behavior Scale for toddlers. The video-taped observations were scored
using the Child and Maternal Behavior Rating Scales. OUTCOMES AND RESULTS: Low
levels of parental discipline and child initiation were found. Parental
responsivity was positively related to child attention and initiation.
CONCLUSIONS AND IMPLICATIONS: Compared to children with no or other levels of
disabilities, this target group exhibits large differences in frequency levels
and, to a lesser extent, the concrete operationalization of parenting domains.
Further, this study confirms the importance of sensitive responsivity as the
primary variable in parenting research.
PMID- 28407536
TI - "Rare place where I feel normal": Perceptions of a social support conference
among parents of and people with Moebius syndrome.
AB - BACKGROUND: Moebius syndrome is a rare congenital disorder resulting in impaired
facial and eye movement. People with rare diseases like Moebius syndrome
experience stigma and a lack of specialized information. Support conferences may
provide important forms of social support for people with rare disorders. AIMS:
To examine reasons for attending, benefits, and limitations of support
conferences. METHODS AND PROCEDURES: 50 adults with Moebius syndrome and 57
parents of people with Moebius syndrome completed open-ended items in an online
study. OUTCOMES AND RESULTS: Mixed- methods content analysis revealed that
companionship and informational support were most frequently mentioned as reasons
for and benefits of attending. Finances were the most frequently mentioned reason
for not attending. Parents were more likely than people with Moebius to describe
instrumental support as a conference benefit. When describing conference
limitations, parents were significantly more concerned by lack of information
relevance, while people with Moebius noted more often that conference attributes
were not relevant to their age. CONCLUSIONS AND IMPLICATIONS: Being surrounded by
others who share one's condition offers a unique opportunity for destigmatizing
companionship support, which normalizes, reduces isolation, and promotes
solidarity. Ways to increase facilitators and decrease barriers to accessing
support for rare disorders should be investigated.
PMID- 28407537
TI - CO2 emissions from the 2010 Russian wildfires using GOSAT data.
AB - In the summer of 2010, more than 6 hundred wildfires broke out in western Russia
because of an unprecedented intense heat wave that resulted from strong
atmospheric blocking. The present study evaluated the CO2 emissions using GOSAT
(Greenhouse gases Observing SATellite) data from July 23 to August 18, 2010 for
western Russia. The results demonstrated that the GOSAT CAI (Cloud and Aerosol
Imager) was well-suited for the identification of smoke plumes and that the GOSAT
FTS (Fourier-Transform Spectrometer) TIR (Thermal InfraRed) could be used to
calculate the height of the plumes at approximately 800 hPa (1.58 km). Using
GOSAT data, we estimated that the 2010 fires in western Russia emitted 255.76 Tg
CO2. We also calculated the CO2 emissions by employing the Biomass Burning Model
(BBM) for the same study site and obtained a similar result of 261.82-302.48 Tg
CO2. The present study proposes a new method for the evaluation of CO2 emissions
from a wildfire using remote sensing data, which could be used to improve the
knowledge of the burning of biomass at a regional or a continental scale, to
reduce the uncertainties in modeling greenhouse gases emissions, and to further
understand how wildfires impact the atmospheric carbon cycle and global warming.
PMID- 28407538
TI - Microwave pyrolysis of textile dyeing sludge in a continuously operated auger
reactor: Char characterization and analysis.
AB - Textile dyeing sludge (DS) contains toxic organic and inorganic substances, and
needs to be disposed by appropriate technologies. This paper investigated an
auger pyrolyser under microwave irradiation for treatment and disposal of DS.
Microwave power, temperature, gas and solid residence times, addition of
catalysts were studied. The results showed that the char yield gradually
decreased with microwave power. The residence times of solid and gas have slight
effects on char yields in the temperature range of 450-750 degrees C. Addition of
CaO and Fe increased char yield, decreased non-condensable gas yield and
increased H2 content. CaO promoted decomposition of DS and capture of CO2. In the
meantime, CaO retained more sulfur in the solid phase compared to MWP without
addition of CaO. The content of C, H and N in DS and sludge char (SC) decreased
with temperature while S increased. The maximum BET (Brunauer-Emmett-Teller)
surface area of 91.9m2/g was observed for SC at 550 degrees C, consistent with
Scanning Electron Microscopy (SEM) observations. X-Ray fluorescence (XRF)
analysis showed existence of some heavy metals, and leaching characteristics of
heavy metals in the SC meet the requirements of national standards in China and
will not pose a threat to the environments.
PMID- 28407539
TI - The single and joint toxicity effects of chlorpyrifos and beta-cypermethrin in
zebrafish (Danio rerio) early life stages.
AB - Water environment pollution caused by the widespread application of beta
cypermethrin (BCP) and chlorpyrifos (CPF) in agriculture has attracted extensive
concern of the world. In this study, zebrafish was used as a model to investigate
the individual and joint toxicity of BCP and CPF. In the acute toxicity test, 3
hpf embryos were exposed to various concentrations of CPF, BCP and their binary
mixtures (MIX) for 96h. The results indicated that these two pesticides and
mixtures induced malformation and death in larvae, and affected hatchability.
These two pesticides in mixtures were verified to act together in a synergistic
manner under experimental conditions. Oxidative stress assaying manifested that
CPF, BCP and MIX altered CAT, SOD and GST activities and MDA content, resulting
in oxidative damage in larvae. By pathology analysis, CPF (236MUg/L), BCP
(5.9MUg/L) and MIX (236MUg/L CPF+5.9MUg/L BCP) were found to trigger liver
lesions and promote apoptosis in tissues. The transcriptome sequencing suggested
that ECM- receptor interaction, focal adhesion, cell cycle, DNA replication,
phototransduction and adherens junction pathways were closely associated with the
toxicity of these two pesticides.
PMID- 28407540
TI - A novel study based on adaptive metal tolerance behavior in fungi and SEM-EDX
analysis.
AB - Four fungal isolates: Simplicillium chinense (iso 9, accession no. KX425621),
Penicillium simplicissimum (iso 10, KP713758), Trichoderma asperellum (iso 11,
KP792512), and Coriolopsis sp. (1c3, KM403574) were subjected to a series of
induced-tolerance training under high metal concentrations to determine if
greater tolerance could be achieved from constant exposure to such conditions.
Adaptive tolerance assay (Tolerance Index, TI) and Field-Emission Scanning
Electron Microscopy with Energy Dispersive X-ray (SEM-EDX) characterized their
metal tolerance. "Untrained" S. chinense, P. simplicissimum and T. asperellum
showed tolerance towards 4000-4500ppm Al(III) (TI: 0.64-0.71), 1000ppm Cr(III)
(0.52-0.83) and Pb(II) (0.32-0.88). With tolerance training, tolerance towards
2000-6000ppm Al(III), 500-3000ppm Pb(II) and 2000-3000ppm Cr(III) were achieved
(TI: 0.01-0.82) compared to untrained cultures (0.00-0.59). In contrast,
tolerance training for Coriolopsis sp. and P. simplicissimum was less successful,
with TI values similar or lower than untrained cultures. SEM-EDX analysis
proposed biosorption and bioaccumulation as mechanisms for metal removal. The
latter was demonstrated with the removal of Cr(III) and Pb(II) by S. chinense
(12.37 and 11.52mgg-1, respectively) and T. asperellum (10.44 and 7.50mgg-1).
Induced-tolerance training may render benefit in the long run, but this delicate
approach is suggestively species and metal dependent.
PMID- 28407541
TI - Sorption mechanisms of chromate with coprecipitated ferrihydrite in aqueous
solution.
AB - Hexavalent chromium (Cr(VI)) attracted researchers' interest for its toxicity,
natural availability and removal difficulty. Nevertheless, its sorption mechanism
is not clearly understood yet. In this work, we elucidated the sorption mechanism
of the co-precipitation of chromates with ferrihydrite through quantitative
analysis. The influence of Cr/Fe molar ratio on sorption was investigated by zeta
potential measurements, X-ray diffraction (XRD) and X-ray adsorption fine
structure analysis (XAFS). Coprecipitation at pH 5 showed almost twice the
sorption density of adsorption at pH 5. In co-precipitation, a shift of the XRD
peak due to inner-sphere sorption of chromate was observed at Cr/Fe molar ratio
0.5. For adsorption, the same peak shift was confirmed at Cr/Fe molar ratio of 1.
Zeta potential at pH 5 suggested that the sorption mechanism changed at Cr/Fe
molar ratio 0.25 for coprecipitation and at Cr/Fe molar ratio of 1 for
adsorption. Fitting of Cr and Fe K-edge extended X-ray adsorption fine-structure
suggested that ferrihydrite immobilized Cr(VI) via outer sphere surface
complexation for lower Cr/Fe ratios and via inner-sphere surface complexation for
higher molar ratios. At higher molar ratios, bidentate binuclear CrFe bonds were
well established, thus resulting in the expansion of the ferrihydrite structure.
PMID- 28407542
TI - Diclofenac degradation in water by FeCeOx catalyzed H2O2: Influencing factors,
mechanism and pathways.
AB - The degradation of diclofenac in a like Fenton system, FeCeOx-H2O2, was studied
in details. The influencing factors, reaction kinetics, reaction mechanism and
degradation pathways of diclofenac were investigated. The optimum conditions were
at a solution pH of 5.0, H2O2 concentration of 3.0mmol/L, diclofenac initial
concentration of 0.07mmol/L, FeCeOx dosage of 0.5g/L, and 84% degradation of
diclofenac was achieved within 40min. The kinetics of FeCeOx catalyzed H2O2
process involved adsorption-dominating and degradation-dominating stages and
fitted pseudo-second order model and pseudo-first order model, respectively.
Singlet oxygen 1O2 was the primary intermediate oxidative species in the
degradation process; superoxide radical anion O2- also participated in the
reaction. The surface cerium and iron sites and the oxygen vacancies in the
FeCeOx catalyst were proposed to play an important role in H2O2 decomposition and
active species generation. The detected intermediates were identified as
hydroxylated derivatives (m/z of 310, 326 and 298), quinone imine compounds (m/z
of 308, 278 and 264) and hydroxyl phenylamine (m/z of 178). The majority
intermediates were hydroxylated derivatives and the minority was hydroxyl
phenylamine. The degradation pathways were proposed to involve hydroxylation,
decarboxylation, dehydrogenation and CN bond cleavage.
PMID- 28407543
TI - Subjective and physiological effects, and expired carbon monoxide concentrations
in frequent and occasional cannabis smokers following smoked, vaporized, and oral
cannabis administration.
AB - BACKGROUND: Although smoking is the most common cannabis administration route,
vaporization and consumption of cannabis edibles are common. Few studies directly
compare cannabis' subjective and physiological effects following multiple
administration routes. METHODS: Subjective and physiological effects, and expired
carbon monoxide (CO) were evaluated in frequent and occasional cannabis users
following placebo (0.001% Delta9-tetrahydrocannabinol [THC]), smoked, vaporized,
and oral cannabis (6.9% THC, ~54mg). RESULTS: Participants' subjective ratings
were significantly elevated compared to placebo after smoking and vaporization,
while only occasional smokers' ratings were significantly elevated compared to
placebo after oral dosing. Frequent smokers' maximum ratings were significantly
different between inhaled and oral routes, while no differences in occasional
smokers' maximum ratings between active routes were observed. Additionally, heart
rate increases above baseline 0.5h after smoking (mean 12.2bpm) and vaporization
(10.7bpm), and at 1.5h (13.0bpm) and 3h (10.2bpm) after oral dosing were
significantly greater than changes after placebo, with no differences between
frequent and occasional smokers. Finally, smoking produced significantly
increased expired CO concentrations 0.25-6h post-dose compared to vaporization.
CONCLUSIONS: All participants had significant elevations in subjective effects
after smoking and vaporization, but only occasional smokers after oral cannabis,
indicating partial tolerance to subjective effects with frequent exposure. There
were no differences in occasional smokers' maximum subjective ratings across the
three active administration routes. Vaporized cannabis is an attractive
alternative for medicinal administrations over smoking or oral routes; effects
occur quickly and doses can be titrated with minimal CO exposure. These results
have strong implications for safety and abuse liability assessments.
PMID- 28407544
TI - Clinical variables associated with poor outcome from sepsis-associated acute
kidney injury and the relationship with timing of initiation of renal replacement
therapy.
AB - PURPOSE: Identify clinical variables associated with mortality in patients with
sepsis-associated acute kidney injury (SA-AKI) receiving continuous renal
replacement therapy (CRRT) and examine timing of initiation of CRRT in reference
to those variables identified. METHODS: Retrospective study conducted at two
tertiary care hospitals including 939 septic shock patients with SA-AKI who
received CRRT in the intensive care unit (ICU). Cox regression models were used
to identify variables associated with 90-day mortality. Timing of CRRT initiation
was assessed in relationship to significant clinical variables identified.
RESULTS: Overall 90-day mortality was 62.9%. Variables prior to CRRT associated
with 90-day mortality included: age (aHR, 1.02; 95%CI, 1.01-1.02, p<000.1), APS
III score (1.01, 1.0-1.0, p<0.048), days from hospital admission to CRRT
initiation (1.01, 1.0-1.0, p<0.01), blood urea nitrogen (1.01, 1.0-1.0, p<0.04),
medical admission (1.76, 1.5-2.1, p<0.0001), creatinine (0.99, 0.9-1.0, p<0.001),
and urine output (0.77, 0.6-0.9, p=0.049). In patients with advanced SA-AKI at
ICU admission receiving CRRT within the first 5days (n=433), urine output during
the 24h prior to CRRT initiation was a strong predictor of survival (2.6, 1.6
4.3, p<0.001). CONCLUSIONS: In patients with SA-AKI, survival is lower when CRRT
is started in the setting of low urine output.
PMID- 28407545
TI - Application of synthetic iron-oxide coated zeolite for the pollution control of
river sediments.
AB - Contaminants released from river sediments are catching more attentions for river
environmental management, especially when external sources of river pollution
have been well controlled. To reduce the contaminant release from sediments, in
situ capping is often applied because of its effective reduction of contaminant
flux and minimal disturbance to the surroundings. As an innovative sediment
capping material, iron-oxide coated zeolite (IOCZ) was synthesized,
characterized, and evaluated in this study. Its performance for the NH4+-N, PO43-
P, and S2--S fixation in aqueous solutions was evaluated using batch and fixed
bed column experiments. IOCZ was found effective as a sorbent for NH4+-N, PO43-
P, and S2--S with the maximum Langmuir sorption capacities of 6.23 mg N g-1,
0.966 mg P g-1, and 1.70 mg S g-1, respectively. Under the studied conditions,
the whole breakthrough process in the fixed-bed column could be well described by
Thomas model, indicating IOCZ can effectively retard NH4+-N, PO43--P, and S2--S
under flowing conditions. In addition, desorption simulative experiments
suggested that the retarded pollutants were stable even under some extreme
environments such as flooding or tiding. Therefore, IOCZ seems a promising
capping material to control the release of NH4+-N, H2PO4--P, and S2--S from river
sediments.
PMID- 28407546
TI - Exploring adduct formation between human serum albumin and eleven organophosphate
ester flame retardants and plasticizers using MALDI-TOF/TOF and LC-Q/TOF.
AB - Organophosphate (OP) and organophosphate ester (OPE) adducts of albumin are
valuable biomarkers for retrospective verification of exposure. In the present
study, our goal was to determine whether OPE flame retardants (OPE FRs) and OPE
plasticizers can covalently bind to human serum albumin (HSA), which would allow
the resulting adducts to be used to evaluate exposure. Eleven OPE FRs and
plasticizers were examined in a HSA-adduct in vitro assay. Pure HSA was incubated
with the target OPEs, as well as with an OP insecticide (profenofos) positive
control. After enzymatic cleavage with pepsin or Glu-C, the digested albumin was
analyzed by matrix-assisted laser desorption ionization tandem time-of-flight
mass spectrometry (MALDI-TOF/TOF-MS) and liquid chromatography-quadrupole time-of
flight mass spectrometry (LC-Q-ToF-MS). Under optimized HSA assay conditions,
tyrosine adducts were formed at Y411 and Y148/Y150 with a characteristic mass
shift for phosphorylation (Deltam/z 166) for the profenofos positive control.
However, no such phosphorylated peptides were detected for the 11 target OPEs.
This negative result suggests that these OPEs have very different affinities from
the OP insecticide. They are less reactive or they may specifically interact with
other proteins.
PMID- 28407547
TI - Biotransformation of copper oxide nanoparticles by the pathogenic fungus Botrytis
cinerea.
AB - Two plant pathogenic fungi, Botrytis cinerea and Alternaria alternata, isolated
from crop plants, were exposed to Cu in ionic (Cu2+), microparticulate (MP, CuO)
or nanoparticulate (NP, Cu or CuO) form, in solid and liquid culturing media in
order to test fungal response and toxic effects of the mentioned compounds for
the potential use as fungicides. B. cinerea has shown pronounced growth and lower
levels of lipid peroxidation compared to A. alternata. Its higher
resistance/tolerance is attributed mainly to biotransformation of CuO and Cu NPs
and CuO MPs into a blue compound at the fungal/culturing media interface,
recognized by Cu K-edge EXAFS analysis as Cu-oxalate complex. The pronounced
activity of catechol-type siderophores and organic acid secretion in B. cinerea
induce leaching and mobilization of Cu ions from the particles and their further
complexation with extracellularly secreted oxalic acid. The ability of pathogenic
fungus to biotransform CuO MPs and NPs hampers their use as fungicides. However
the results show that B. cinerea has a potential to be used in degradation of
Cu(O) nanoparticles in environment, copper extraction and purification
techniques.
PMID- 28407548
TI - Adsorption and reaction mechanism of arsenic vapors over gamma-Al2O3 in the
simulated flue gas containing acid gases.
AB - Arsenic emission from fuel combustion and metal smelting flue gas causes serious
pollution. Addition of sorbents is a promising way for the arsenic capture from
high temperature flue gas. However, it is difficult to remove arsenic from
SO2/HCl-rich flue gas due to the competitive reaction of the sorbents with
arsenic and these acid gases. To solve this problem, arsenic adsorption over
gamma-Al2O3 was studied in this work to evaluate its adsorption mechanism,
resistance to acid gases as well as regeneration behavior. The results show that
gamma-Al2O3 had good resistance to acid gases and the arsenic adsorption by gamma
Al2O3 could be effectively carried out at a wide temperature range between 573
and 1023 K. Nevertheless, adsorption at higher-temperature (like 1173 K) leaded
to the decrease of surface area and the rearrangement of crystal structure of
gamma-Al2O3, reducing the active sites for arsenic adsorption. The adsorption of
arsenic was confirmed to occur at different active sites in gamma-Al2O3 by
forming various adsorbed species. Increasing temperature facilitated arsenic
transformation into more stable chemisorbed As3+ and As5+ which were difficult to
remove through thermal treatment regeneration. Fortunately, the regeneration of
spent gamma-Al2O3 could be well performed using NaOH solution.
PMID- 28407549
TI - Estrogenicity assessment of membrane concentrates from landfill leachate treated
by the UV-Fenton process using a human breast carcinoma cell line.
AB - Membrane concentrates (MCs) are generated when membranes are used to concentrate
landfill leachate. It contains high concentrations of inorganic and organic
environmental pollutants, which are highly toxic and carcinogenic. In this paper,
the proliferation effect (PE) from MC before and after treatment with the UV
Fenton process was assessed using the human breast carcinoma cell line MCF-7. The
highest value of 116% was found at 5% (v/v) concentration after a 10 min
reaction. Phthalic acid esters (PAEs) play an important role in the MC
estrogenicity. Estrogen simulation solutions (ESS) of PAEs were prepared to
simulate the changes in estrogenic active substances during the UV-Fenton
process. The ESS degradation conformed to the first-order kinetics model. The
estrogenicity decreased after an initial increase until it acted in a non
estrogenic manner. Convincingly, the intermediates were determined by GC/MS, and
the estrogenicity was assessed during the degradation process. The estrogenicity
was highly related to the generation of intermediates and the PAE concentration.
The results provide guidance for UV-Fenton application in MC estrogenicity
reduction.
PMID- 28407550
TI - Potential phosphorus eutrophication mitigation strategy: Biochar carbon
composition, thermal stability and pH influence phosphorus sorption.
AB - Phosphorus (P) eutrophication is a major pollution problem globally, with
unprecedented amount of P emanating from agricultural sources. But little is
known about the optimization of soil-biochar P sorption capacity. The study
objective was to determine how biochar feedstocks and pyrolysis conditions
influences carbon (C) thermal stability, C composition and pH and in turn
influence the phosphorus sorption optimization. Biochar was produced from
switchgrass, kudzu and Chinese tallow at 200, 300, 400, 500, 550, 650,750
degrees C. Carbon thermal stability was determined by multi-element scanning
thermal analysis (MESTA), C composition was determined using solid state 13C NMR.
Phosphorus sorption was determined using a mixture of 10% biochar and 90% sandy
soil after incubation. Results indicate increased P sorption (P < 0.0001) and
decreased P availability (P < 0.0001) with increasing biochar pyrolysis
temperature. However, optimum P sorption was feedstock specific with switchgrass
indicating P desorption between 200 and 550 degrees C. Phosphorus sorption was
in the order of kudzu > switchgrass > Chinese tallow. Total C, C thermal
stability, aromatic C and alkalinity increased with elevated pyrolysis
temperature. Biochar alkalinity favored P sorption. There was a positive
relationship between high thermal stable C and P sorption for Kudzu (r = 0.62; P
= 0.0346) and Chinese tallow (r = 0.73; P = 0.0138). In conclusion, biochar has
potential for P eutrophication mitigation, however, optimum biochar pyrolysis
temperature for P sorption is feedstock specific and in some cases might be out
of 300-500 degrees C temperature range commonly used for agronomic application.
High thermal stable C dominated by aromatic C and alkaline pH seem to favor P
sorption.
PMID- 28407551
TI - Plasma adiponectin levels, ADIPOQ variants, and incidence of type 2 diabetes: A
nested case-control study.
AB - AIMS: To clarify the associations between plasma adiponectin levels and ADIPOQ
variants with type 2 diabetes incidence in a general Japanese population.
METHODS: We conducted a case-control study nested within the Japan Public Health
Center-based Prospective Study. We measured plasma adiponectin levels and
genotyped +45T>G (rs2241766) and +276G>T (rs1501299) in the ADIPOQ gene among 417
incident diabetes cases and 1197 control subjects matched by age, sex, and area.
RESULTS: After potential confounding factor adjustment, the multivariable
adjusted diabetes odds ratios (ORs) were 0.59 (95% confidence interval [CI]: 0.51
0.68) and 0.68 (95% CI: 0.60-0.78) per 1 standard deviation increment in the log
transformed levels of total- and high-molecular-weight (HMW) adiponectin levels,
respectively. However, the ADIPOQ variants were not significantly associated with
plasma adiponectin levels (for total adiponectin, +45 P=0.15 and +276 P=0.08) and
diabetes risk (+45 P=0.70 and +276 P=0.72) under the additive genetic model.
CONCLUSIONS: Our prospective findings suggest that both total and HMW adiponectin
levels are strongly and inversely associated with diabetes risk after adjustment
for potential confounding factors; however, the ADIPOQ variants +45 and +276 are
not associated with adiponectin levels and diabetes risk in the general Japanese
population.
PMID- 28407552
TI - Physician-patient communication at diagnosis of type 2 diabetes and its links to
patient outcomes: New results from the global IntroDia(r) study.
AB - AIMS: To investigate patient experiences during the diagnosis of type 2 diabetes
mellitus (T2DM), focusing on how physician-patient communication at diagnosis
influences patients' psychosocial stress and subsequent self-management and
outcomes. METHODS: We surveyed adults with T2DM in 26 countries in a large cross
national study of physician-patient communication during early T2DM treatment
(IntroDia(r)). The self-report questionnaire assessed retrospectively patient
experiences during diagnosis conversations (focusing on 43 possible
conversational elements, and communication quality) and potential effects on
patient-reported outcomes. RESULTS: Data from 3628 people with T2DM who had been
prescribed oral treatment at diagnosis were analysed. Exploratory factor analyses
of the conversational elements yielded four coherent, meaningful factors:
Encouraging (Cronbach's alpha=0.86); Collaborative (alpha=0.88); Recommending
Other Resources (alpha=0.75); and Discouraging (alpha=0.72). Patient-perceived
communication quality (PPCQ) at diagnosis was positively associated with
Encouraging (beta=+1.764, p<0.001) and Collaborative (beta=+0.347, p<0.001),
negatively associated with Discouraging (beta=-1.181, p<0.001) and not associated
with Recommending Other Resources (beta=+0.087, p=0.096), using a stable path
model. PPCQ was associated with less current diabetes distress, greater current
well-being and better current self-care. Conversation elements comprising factors
associated with better PPCQ (Encouraging and Collaborative) were recalled more
frequently by patients than elements associated with poor PPCQ (Discouraging).
CONCLUSIONS: Better physician-patient communication at T2DM diagnosis may
contribute to subsequent greater patient well-being and self-care, and may be
enhanced by greater physician use of Collaborative and Encouraging conversation
elements.
PMID- 28407553
TI - High frequency repetitive transcranial magnetic stimulation treatment for major
depression: Dissociated effects on psychopathology and neurocognition.
AB - OBJECTIVES: This open-label pilot study explored the effects of a course of
accelerated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS)
on two neurocognitive domains (decision-making and impulse control) in patients
with major depressive disorder (MDD). METHODS: Participants with MDD and a
treatment resistant major depressive episode (n=24) underwent twice-daily HF-rTMS
targeted at the left dorsolateral prefrontal cortex (lDLPFC) over two weeks.
Psychopathology was assessed by clinician-administered and self-reported measures
of depression and anxiety; decision-making was assessed by the Iowa Gambling
Task, the Balloon Analog Risk Task and the Game of Dice Task; impulse control was
assessed by the Stroop Color-Word Task, the Continuous Performance Task and the
Stop-Signal Task. RESULTS: Depression and anxiety scores significantly improved
from pre-post HF-rTMS treatment. However, none of the decision-making or impulse
control variables of interest changed significantly from pre-post HF-rTMS.
Moreover, there was no correlation between changes in psychopathological symptoms
and in neurocognition. LIMITATIONS: This is a moderately sized open label trial,
and the confounds of ongoing psychotropics and illness chronicity can not be
excluded in this treatment resistant sample. CONCLUSIONS: There is dissociation
between acute symptomatic benefit after a course of accelerated HF-rTMS applied
to the lDLPFC in treatment resistant MDD and performance on tests of decision
making and impulse control. Though rTMS appears cognitively safe, additional
research is warranted to understand this potential dissociation and its putative
clinical implications.
PMID- 28407555
TI - Thalamocortical connectivity in major depressive disorder.
AB - BACKGROUND: Major Depressive Disorder (MDD) is highly prevalent and potentially
devastating, with widespread aberrations in brain activity. Thalamocortical
networks are a potential candidate marker for psychopathology in MDD, but have
not yet been thoroughly investigated. Here we examined functional connectivity
between major cortical areas and thalamus. METHOD: Resting-state fMRI from 54 MDD
patients and 40 healthy controls were collected. The cortex was segmented into
six regions of interest (ROIs) consisting of frontal, temporal, parietal, and
occipital lobes and pre-central and post-central gyri. BOLD signal time courses
were extracted from each ROI and correlated with voxels in thalamus, while
removing signals from every other ROI. RESULTS: Our main findings showed that MDD
patients had predominantly increased connectivity between medial thalamus and
temporal areas, and between medial thalamus and somatosensory areas. Furthermore,
a positive correlation was found between thalamo-temporal connectivity and
severity of symptoms. LIMITATIONS: Most of the patients in this study were not
medication naive and therefore we cannot rule out possible long-term effects of
antidepressant use on the findings. CONCLUSION: The abnormal connectivity between
thalamus and temporal, and thalamus and somatosensory regions may represent
impaired cortico-thalamo-cortical modulation underlying emotional, and sensory
disturbances in MDD. In the context of similar abnormalities in thalamocortical
systems across major psychiatric disorders, thalamocortical dysconnectivity could
be a reliable transdiagnostic marker.
PMID- 28407554
TI - Transdiagnostic differences in the resting-state functional connectivity of the
prefrontal cortex in depression and schizophrenia.
AB - BACKGROUND: Depression and schizophrenia are two of the most serious psychiatric
disorders. They share similar symptoms but the pathology-specific commonalities
and differences remain unknown. This study was conducted to acquire a full
picture of the functional alterations in schizophrenia and depression patients.
METHODS: The resting-state fMRI data from 20 patients with schizophrenia, 20
patients with depression and 20 healthy control subjects were collected. A data
driven approach that included local functional connectivity density (FCD)
analysis combined with multivariate pattern analysis (MVPA) was used to compare
the three groups. RESULTS: Based on the results of the MVPA, the local FCD value
in the orbitofrontal cortex (OFC) can differentiate depression patients from
schizophrenia patients. The patients with depression had a higher local FCD value
in the medial and anterior parts of the OFC than the subjects in the other two
groups, which suggested altered abstract and reward reinforces processing in
depression patients. Subsequent functional connectivity analysis indicated that
the connection in the prefrontal cortex was significantly lower in people with
schizophrenia compared to people with depression and healthy controls.
LIMITATION: The systematically different medications for schizophrenia and
depression may have different effects on functional connectivity. CONCLUSIONS:
These results suggested that the resting-state functional connectivity pattern in
the prefrontal cortex may be a transdiagnostic difference between depression and
schizophrenia patients.
PMID- 28407556
TI - Functional network-based statistics in depression: Theory of mind subnetwork and
importance of parietal region.
AB - OBJECTIVE: The functional network analysis of whole brain is an emerging field
for research in depression. We initiated this study to investigate which
subnetwork is significantly altered within the functional connectome in major
depressive disorder (MDD). METHODS: The study enrolled 52 first-episode
medication-naive patients with MDD and 40 controls for functional network
analysis. All participants received the resting-state functional imaging using a
3-Tesla magnetic resonance scanner. After preprocessing, we calculated the
connectivity matrix of functional connectivity in whole brain for each subject.
The network-based statistics of connectome was used to perform group comparisons
between patients and controls. The correlations between functional connectivity
and clinical parameters were also performed. RESULTS: MDD patients had
significant alterations in the network involving "theory of mind" regions, such
as the left precentral gyrus, left angular gyrus, bilateral rolandic operculums
and left inferior frontal gyrus. The center node of significant network was the
left angular gyrus. No significant correlations of functional connectivity within
the subnetwork and clinical parameters were noted. CONCLUSION: Functional
connectivity of "theory of mind" subnetwork may be the core issue for
pathophysiology in MDD. In addition, the center role of parietal region should be
emphasized in future study.
PMID- 28407557
TI - Temperament traits in suicidal and non-suicidal mood disorder patients in Taiwan.
AB - Suicide is a major social and clinical problem in Asia. Although studies have
suggested that personality traits are possible risk factors for suicide, no study
has been conducted among Chinese to compare the temperament traits of suicidal
and non-suicidal mood disorder patients with those of healthy controls. This
study compared temperament traits of two patient groups, those with a mood
disorder who have attempted suicide (n=204), and those with a mood disorder who
have not attempted suicide (n=160), and compared the traits of these patients to
those of healthy controls (n=178), assessed by Cloninger's Tridimensional
Personality Questionnaire and the Brown-Goodwin Aggression Inventory. Patients
with suicidal attempts had significantly higher novelty seeking and aggression
scores than healthy controls and patients without suicidal attempts. Two groups
of patients with mood disorder had significantly higher harm avoidance scores
than the healthy controls. However, patients with suicidal attempts did not have
higher harm avoidance scores than patients without suicidal attempts. This study
confirms findings that harm avoidance and mood disorder are related, and extends
them by suggesting that those with a mood disorder and suicide attempts have
higher novelty seeking and lifetime aggression scores than those without suicidal
attempt, either patients or healthy controls.
PMID- 28407558
TI - CD11b regulates antibody class switching via induction of AID.
AB - The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is
primarily expressed on the surface of innate immune cells. Genetic variations in
ITGAM are among the strongest risk factors for systemic lupus erythematosus, an
autoimmune disease characterized by the presence of autoantibodies. However, the
regulatory function of CD11b in the antibody responses remains unclear. Here, we
report the induction of CD11b in activated B2 B cells and define its unexpected
role in immunoglobulin heavy chain class switch recombination (CSR). LPS
activated B cells lacking CD11b yielded fewer IgG subtypes such as IgG1 and IgG2a
in vitro, and immunization-dependent CSR and affinity maturation of antibodies
were severely impaired in CD11b-deficient mice. Notably, we observed the reduced
expression of activation-induced cytidine deaminase (AID), an enzyme that
initiates CSR and somatic hypermutation, and ectopic expression of AID was
sufficient to rescue the defective CSR of CD11b-deficient B cells. LPS-induced
phosphorylation of NF-kappaB p65 and IkappaBalpha was attenuated in CD11b
deficient B cells, and hyperactivation of IkappaB kinase 2 restored the defective
AID expression and CSR, which implied that CD11b regulates the NF-kappaB
dependent induction of AID. Overall, our experimental evidence emphasized the
function of CD11b in antibody responses and the role of CD11b as a vital
regulator of CSR.
PMID- 28407559
TI - Positive feedback effect of PGE2 on cyclooxygenase-2 expression is mediated by
inhibition of Akt phosphorylation in human follicular dendritic cell-like cells.
AB - Prostaglandins (PGs) are bioactive lipid mediators generated from the
phospholipids of cell membrane in response to various inflammatory signals. To
understand the potential role of PGs in PG production itself during immune
inflammatory responses, we examined the effect of PGE2, PGF2alpha, and beraprost
on COX-2 expression using follicular dendritic cell (FDC)-like HK cells isolated
from human tonsils. Those three PGs specifically augmented COX-2 protein
expression in a dose-dependent manner after 4 or 8h of treatment. The enhancing
effect was also reflected in the actual production of PGs and the viable cell
recovery of germinal center B-cells. To investigate the underlying molecular
mechanism, we examined the impact of PI3K inhibitors on PG-induced COX-2
expression. Interestingly, COX-2 induction by PGE2 and beraprost, but not
PGF2alpha, was enhanced by wortmannin and LY294002. In line with this result, Akt
phosphorylation was inhibited by PGE2 and beraprost but not by PGF2alpha. The
distinct effect of PGE2 and beraprost from PGF2alpha was reproduced in Akt
knockdowned HK cells. Our current findings imply that PGE2 and PGI2 stimulate COX
2 expression in FDC by inhibiting Akt phosphorylation. Additional studies are
warranted to determine the potential role of Akt as a therapeutic target in
patients with inflammatory disorders.
PMID- 28407560
TI - Genital and anal injuries: A cross-sectional Australian study of 1266 women
alleging recent sexual assault.
AB - OBJECTIVES: To describe the frequency of genital and anal injury and associated
demographic and assault characteristics in women alleging sexual assault. DESIGN:
Cross-sectional study. SETTING: Sexual Assault Resource Centre (SARC), Western
Australia. PARTICIPANTS: Total of 1266 women attending SARC from Jan-2009 to Mar
2015. METHODS: Women underwent a standardised data collection procedure by
forensically trained doctors. Multivariate logistic regression analyses were
performed. MAIN OUTCOME MEASURES: (1) Frequency of genital and anal injuries by
type of sexual assault. (2) Identification of independent factors associated with
genital and anal injuries following, respectively, completed vaginal and anal
penetration. RESULTS: Genital injury was observed in 24.5% of all women with
reported completed vaginal penetration; in a subset with no prior sexual
intercourse 52.1% had genital injury. Genital injury was more likely with no
prior sexual intercourse (adjusted odds ratio [adj. OR] 4.4, 95% confidence
interval [95%CI] 2.4-8.0), multiple types of penetrants (adj. OR 1.5, 95%CI 1.0
2.1), if general body injury present and less likely with sedative use and
delayed examination. Anal injury, observed in 27.0% of reported completed anal
penetrations, was more likely with multiple types of penetrants (adjusted OR 5.0,
95%CI 1.2-21.0), if general body injury present and less likely with delayed
examination. CONCLUSION: This study separately quantifies the frequency of both
genital and anal injuries in sexually assaulted women. Genital injuries were
absent in a large proportion of women regardless of prior vaginal intercourse
status. It is anticipated that findings will better inform the community, police
and medico-legal evidence to the criminal justice system.
PMID- 28407561
TI - Correlation between cervical artery kinking and white matter lesions.
AB - OBJECTIVE: To explore the correlation between cervical artery (i.e., extracranial
carotid artery and vertebral artery) kinking and white matter lesions (WMLs).
PATIENTS AND METHODS: In total, 147 patients who underwent magnetic resonance
imaging (MRI) of the head and computed tomography angiography (CTA) of the head
and neck were included in this study. The severity score of WMLs in each patient
was evaluated using MRI data. The extent and location of cervical artery kinking
were determined and recorded using CTA. The correlation between cervical artery
kinking and WMLs was analyzed using logistic regression and Dunnett's method.
RESULTS: The age at which diabetes and carotid artery (common carotid artery and
extracranial internal carotid artery) kinking develop and the rate of incidence
were significantly higher in patients with WMLs than in those with non-WMLS
(P<0.05, P<0.01), but there was no significant difference in the incidence of
vertebral artery kinking. Logistic regression analysis indicated that carotid
artery kinking (OR=6.144, 95% CI: 2.702-13.970), age (OR=1.055, 95% CI: 1.007
1.106), and diabetes (OR=4.636, 95% CI: 1.421-15.126) were risk factors for WMLs
(P<0.01). The Pearson correlation coefficient was 0.753 (P<0.01), thereby
suggesting that there is a positive correlation between the severity of WMLs and
the number of carotid artery kinks. CONCLUSION: Carotid artery kinking may be an
independent risk factor for WMLs.
PMID- 28407562
TI - Synaptic patterning and the timescales of cortical dynamics.
AB - Neocortical circuits, as large heterogeneous recurrent networks, can potentially
operate and process signals at multiple timescales, but appear to be
differentially tuned to operate within certain temporal receptive windows. The
modular and hierarchical organization of this selectivity mirrors anatomical and
physiological relations throughout the cortex and is likely determined by the
regional electrochemical composition. Being consistently patterned and actively
regulated, the expression of molecules involved in synaptic transmission
constitutes the most significant source of laminar and regional variability. Due
to their complex kinetics and adaptability, synapses form a natural primary
candidate underlying this regional temporal selectivity. The ability of cortical
networks to reflect the temporal structure of the sensory environment can thus be
regulated by evolutionary and experience-dependent processes.
PMID- 28407564
TI - Processing of acoustic signals via wavelet & Choi - Williams analysis in three
point bending load of carbon/epoxy and glass/epoxy composites.
AB - In this article, acoustic emission method was used for monitoring of flexural
loading of GFRP (Glass fiber/epoxy composite) and CFRP (Carbon fiber/epoxy
composite) via one acoustical sensor. In order to signal processing, various
methods were employed such as wavelet transform, Short time Fourier transform,
Choi - Williams transform and etc. Using two signal processing methods, wavelet
transform and Choi - Williams transform, for monitoring of GFRP and CFRP
specimens, determines strengths and weaknesses of each method and appointed the
best analysis for signal processing of three point bending load of this type of
composites. Based on information obtained from comparing of CFRP and GFRP, it is
resulted that, the ratio of elastic modules and maximum load bearing of CFRP to
GFRP is 1.36 and 3.25 respectively. Moreover, based on comparing of two analysis
method results, Wavelet analysis was appointed better signal processing method
for this type of load and material.
PMID- 28407565
TI - An integrated approach towards the discovery of novel non-nucleoside Leishmania
major pteridine reductase 1 inhibitors.
AB - Despite the fact that Leishmania ssp are pteridine auxotrophs, Dihydrofolate
Reductase-Thymidylate Synthase (DHFR-TS) inhibitors are ineffective against
Leishmania major. On the other hand Pteridine Reductase 1 (PTR1) inhibitors
proved to be lethal to the parasite. Aiming at identifying hits that lie outside
the chemical space of known PTR1 inhibitors, pharmacophore models that
differentiate true-binders from decoys and explain the structure-activity
relationships of known inhibitors were employed to virtually screen the lead-like
subset of ZINC database. This approach leads to the identification of Z80393
(IC50 = 32.31 +/- 1.18 MUM), whose inhibition mechanism was investigated by
Thermal Shift Assays. This experimental result supports a competitive mechanism
and was crucial to establish the docking search space as well as select the best
pose, which was then investigated by molecular dynamics studies that corroborate
the hit putative binding profile towards LmPTR1. The information gathered from
such studies shall be useful to design more potent non-nucleoside LmPTR1
inhibitors.
PMID- 28407566
TI - "I started working because I was hungry": The consequences of food insecurity for
children's well-being in rural Ethiopia.
AB - Food insecurity, the state of being without reliable access to a sufficient
quantity of safe, nutritious food, is a persistent problem in rural Ethiopia.
However, little qualitative research has explored how food insecurity affects
children over time, from their point of view. What are the effects of economic
'shocks' such as illness, death, loss of livestock, drought and inflation on
availability of food, and children's well-being? To what extent do social
protection schemes (in this case, the Productive Safety Net Programme) mitigate
the long-term effects of food insecurity for children? The paper uses a life
course approach, drawing on analysis of four rounds of qualitative longitudinal
research conducted in 2007, 2008, 2011 and 2014, with eight case study children,
as part of Young Lives, an ongoing cohort study. Children's descriptions of the
importance of food and a varied diet (dietary diversity) in everyday life were
expressed in a range of qualitative methods, including interviews, group
discussions and creative methods. The paper suggests that while the overall
picture of food security in Ethiopia has improved in the past decade, for the
poorest rural families, food insecurity remains a major factor influencing
decisions about a range of matters - children's time allocation, whether to
continue in school, whether to migrate for work, and whether they marry. The
paper argues that experiences of food insecurity need to be understood
holistically, in relation to other aspects of children's lives, at differing
stages of the life-course during childhood. The paper concludes that nutritional
support beyond early childhood needs to be a focus of policy and programming.
PMID- 28407567
TI - Obesity and the Social Withdrawal Syndrome.
AB - The relation between obesity and Social Withdrawal Syndrome (SWS) was examined
using the data gathered by Rotenberg, Bharathi, Davies, and Finch (2013). One
hundred and 35 undergraduates (80 females; Mage=21years-10months) completed
standardized scales that assessed the SWS (low emotional trust beliefs in close
others, low disclosure to close others, and high loneliness). BMI was calculated
from self-reported weight and height. As hypothesized, quadratic relations were
found in which participants with BMI>30 (i.e., obese) demonstrated the SWS
pattern of low emotional trust beliefs in close others, low disclosure to close
others, and high loneliness. As further evidence, lower emotional trust in close
others, lower disclosure to close others, and greater loneliness were found for
obese participants (>30 BMI, n=27) than both normal weight (<25 BMI, n=67) and
overweight participants (25 to 30 BMI, n=41). The findings confirmed the
hypothesis that obesity was associated with the SWS. The findings suggested that
the lack of trust in others by obese individuals contributes to their
unwillingness to seek out help for health and psychosocial problems.
PMID- 28407568
TI - The relation between anorexic symptoms in women and their reports of
trustworthiness in interactions with close persons.
AB - The study examined the relation between women's anorexic symptoms and their
reports of trustworthiness in interactions with close persons. Ninety-eight
females (mean age=24years-10months) completed the anorexic symptom subscale of
the SEDS and reported (ascribed) the extent to which they showed reliability,
emotional, and honesty trustworthiness behaviors in interactions with their
mother, father, and close friend. Negative linear relations were found between
anorexic symptoms and ascribed: (a) trustworthiness with close friends; (b)
reliability trustworthiness; and (c) at a trend level, honesty trustworthiness.
These were qualified by curvilinear relations and by elevated anorexic vs
normative group comparisons. It was found that women with elevated anorexic
symptoms ascribed lower trustworthiness than did women with the normal range of
anorexic symptoms. The findings were interpreted as supporting the conclusion
that women with elevated levels of anorexic symptoms are inclined to believe that
they are deceptive in their interactions with close persons, primarily friends.
PMID- 28407569
TI - Expansion of monocytic myeloid-derived suppressor cells in endometriosis
patients: A pilot study.
AB - Endometriosis is a chronic inflammation disease and is closely associated with
immune dysregulation. Myeloid-derived suppressor cells (MDSCs) are a negative
regulator of the immune system. The aim of this study was to evaluate the
possible role of MDSCs in endometriosis patients. We collected the peripheral
blood and peritoneal fluid from endometriosis patients and controls and analyzed
M-MDSCs level using specific monoclonal antibodies recognizing HLA-DR, CD33,
CD11b, CD14 markers by flow cytometry. We found that there existed abnormal
expansion of monocytic MDSCs (M-MDSCs) (HLA-DR-/lowCD33+CD11b+ CD14+) in
peripheral blood and peritoneal fluid of patients with endometriosis. Functional
studies revealed that M-MDSCs from endometriosis patients significantly
suppressed T-cell responses and produced high level of reactive oxygen species
(ROS). The elevation of M-MDSCs from endometriosis patients may contribute to the
disease progression.
PMID- 28407570
TI - The application of illite supported nanoscale zero valent iron for the treatment
of uranium contaminated groundwater.
AB - In this study, nanoscale zero valent iron I-NZVI was investigated as a
remediation strategy for uranium contaminated groundwater from the former
Cimarron Fuel Fabrication Site in Oklahoma, USA. The 1 L batch-treatment system
was applied in the study. The result shows that 99.9% of uranium in groundwater
was removed by I-NZVI within 2 h. Uranium concentration in the groundwater stayed
around 27 MUg/L, and there was no sign of uranium release into groundwater after
seven days of reaction time. Meanwhile the release of iron was significantly
decreased compared to NZVI which can reduce the treatment impact on the water
environment. To study the influence of background pH of the treatment system on
removal efficiency of uranium, the groundwater was adjusted from pH 2-10 before
the addition of I-NZVI. The pH of the groundwater was from 2.1 to 10.7 after
treatment. The removal efficiency of uranium achieved a maximum in neutral pH of
groundwater. The desorption of uranium on the residual solid phase after
treatment was investigated in order to discuss the stability of uranium on
residual solids. After 2 h of leaching, 0.07% of the total uranium on residual
solid phase was leached out in a HNO3 leaching solution with a pH of 4.03. The
concentration of uranium in the acid leachate was under 3.2 MUg/L which is below
the EPA's maximum contaminant level of 30 MUg/L. Otherwise, the concentration of
uranium was negligible in distilled water leaching solution (pH = 6.44) and NaOH
leaching solution (pH = 8.52). A desorption study shows that an acceptable amount
of uranium on the residuals can be released into water system under strong acid
conditions in short terms. For long term disposal management of the residual
solids, the leachate needs to be monitored and treated before discharge into a
hazardous landfill or the water system. For the first time, I-NZVI was applied
for the treatment of uranium contaminated groundwater. These results provide
proof that I-NZVI has improved performance compared to NZVI and is a promising
technology for the restoration of complex uranium contaminated water resources.
PMID- 28407571
TI - Thermally induced shape memory behavior, enzymatic degradation and
biocompatibility of PLA/TPU blends: "Effects of compatibilization".
AB - Poly(lactic acid) (PLA)/thermoplastic polyurethane (TPU) blends were melt-mixed
and compatibilized to investigate their biocompatibility, biodegradability and
thermally induced shape memory properties. The blend compositions were PLA/TPU:
80/20 (20TPU) and PLA/TPU: 50/50 (50TPU). 1,4-phenylene diisocyanate (PDI) was
used in order to compatibilize the components reactively. The PDI composition was
0.5, 1, 3% by weight. Biodegradability was assessed by enzymatic degradation
tests. Biocompatibility was investigated through in-vitro cell-culture
experiments. Shape memory tests exhibited that 20TPU blends have higher recovery
ratio than that of 50TPU blends. It was observed that the shape recovery ratio
was enhanced by the addition of PDI. The highest shape recovery ratio was
obtained at 3%PDI in 20TPU blends. Enzymatic biodegradability tests showed that
the increasing TPU content decreased the biodegradability of the blends. It was
found that compatibilization slowed down the enzymatic degradation of PLA/TPU
blends. In-vitro cell-culture experiments indicated that all blends were
biocompatible, and no evidence of cytotoxicity was observed.
PMID- 28407572
TI - Synthesis and viscoelastic characterization of microstructurally aligned Silk
fibroin sponges.
AB - Silk fibroin (SF) is a model candidate for use in tissue engineering and
regenerative medicine owing to its bio-compatible mechanochemical properties.
Despite numerous advances made in the fabrication of various biomimetic
substrates using SF, relatively few clinical applications have been designed,
primarily due to the lack of complete understanding of its constitutive
properties. Here we fabricate microstructurally aligned SF sponge using the
unidirectional freezing technique wherein a novel solvent-processing technique
involving Acetic acid is employed, which obviates the post-treatment of the
sponges to induce their water-stability. Subsequently, we quantify the
anisotropic, viscoelastic response of the bulk SF sponge samples by performing a
series of mechanical tests under uniaxial compression over a wide range of strain
rates. Results for these uniaxial compression tests in the finite strain regime
through ramp strain and ramp-relaxation loading histories applied over two orders
of strain rate magnitude show that microstructural anisotropy is directly
manifested in the bulk viscoelastic solid-like response. Furthermore, the
experiments reveal a high degree of volume compressibility of the sponges during
deformation, and also evince for their remarkable strain recovery capacity under
large compressive strains during strain recovery tests. Finally, in order to
predict the bulk viscoelastic material properties of the fabricated and pre
characterized SF sponges, a finite strain kinematics-based, nonlinear, continuum
model developed within a thermodynamically-consistent framework in a parallel
investigation, was successfully employed to capture the viscoelastic solid-like,
transversely isotropic, and compressible response of the sponges macroscopically.
PMID- 28407573
TI - Assessment of mobility and bioavailability of mercury compounds in sewage sludge
and composts.
AB - Content of heavy metals, including mercury, determines the method of management
and disposal of sewage sludge. Excessive concentration of mercury in composts
used as organic fertilizer may lead to accumulation of this element in soil and
plant material. Fractionation of mercury in sewage sludge and composts provides a
better understanding of the extent of mobility and bioavailability of the
different mercury species and helps in more informed decision making on the
application of sludge for agricultural purposes. The experimental setup comprises
the composing process of the sewage sludge containing 13.1mgkg-1 of the total
mercury, performed in static reactors with forced aeration. In order to evaluate
the bioavailability of mercury, its fractionation was performed in sewage sludge
and composts during the process. An analytical procedure based on four-stage
sequential extraction was applied to determine the mercury content in the ion
exchange (water soluble and exchangeable Hg), base soluble (Hg bound to humic and
fulvic acid), acid soluble (Hg bound to Fe/Mn oxides and carbonates) and
oxidizable (Hg bound to organic matter and sulphide) fractions. The results
showed that from 50.09% to 64.55% of the total mercury was strongly bound to
organo-sulphur and inorganic sulphide; that during composting, increase of
concentrations of mercury compounds strongly bound with organic matter and
sulphides; and that mercury content in the base soluble and oxidizable fractions
was strongly correlated with concentration of dissolved organic carbon in those
fractions.
PMID- 28407574
TI - Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses.
AB - BACKGROUND: Seasonal variation of relapses in multiple sclerosis (MS) suggests
that season-dependent factors, such as ambient air pollution, may trigger them.
However, only few studies have considered possible role of air pollutants as
relapse's risk factor. OBJECTIVE: We investigated the effect of particulate
matter of aerodynamic diameter smaller than 10um (PM10) on MS relapses. METHODS:
In total, 536 relapsing MS patients from Strasbourg city (France) were included,
accounting for 2052 relapses over 2000-2009 period. A case-crossover design was
used with cases defined as the days of relapse and controls being selected in the
same patient at plus and minus 35 days. Different lags from 0 to 30 days were
considered. Conditional logistic regressions, adjusted on meteorological
parameters, school and public holidays, were used and exposure was considered
first as a quantitative variable and second, as a binary variable. RESULTS: The
natural logarithm of the average PM10 concentration lagged from 1 to 3 days
before relapse onset was significantly associated with relapse risk (OR =1.40
[95% confidence interval 1.08-1.81]) in cold season. Consistent results were
observed when considering PM10 as a binary variable, even if not significant.
CONCLUSION: With an appropriate study design and robust ascertainment of
neurological events and exposure, the present study highlights the effect of PM10
on the risk of relapse in MS patients, probably through oxidative stress
mechanisms.
PMID- 28407575
TI - FAM83D knockdown regulates proliferation, migration and invasion of colorectal
cancer through inhibiting FBXW7/Notch-1 signalling pathway.
AB - Colorectal cancer is one of the most common malignant tumors in the digestive
system, and in China its incidence is rising in recent years. The FAM83D family
with sequence similarity 83, member D is associated with the occurrence and
development of various cancers. However, in human colorectal cancer, the
biological function of FAM83D and its molecular mechanism are still little known.
In our study, we found that FAM83D mRNA expression level was markedly up
regulated in colorectal cancerous tissues when compared with that of adjacent
normal colon tissues. We also found that the protein and mRNA expression levels
of FAM83D are dramatically increased in human colorectal cancer cell lines,
including Caco-2, RKO, DLD-1, HT-29, LoVo, SW480, and HCT116, especially in SW480
and HCT116 cells, when compared with that of human normal colon epithelial cell
line (NCM460). Next, in HCT116 and SW480 cells, the biological function of FAM83D
was examined. FAM83D-knockdown notably inhibited cell proliferation and colony
formation. Cell apoptosis was promoted by FAM83D knockdown. In addition, FAM83D
siRNA decreased cell migration and invasion. Moreover, FAM83D knockdown up
regulated the protein expression level of F-box and WD repeat domain-containing 7
(FBXW7), but diminished the Notch1 protein expression level. It also found that
FBXW7 siRNA reverses the suppressive effect of FAM83D knockdown on Notch1 protein
expression. Notch1 overexpression reversed the effect of FAM83D knockdown on
colorectal cancer cell proliferation, cell migration and invasion. In conclusion,
FAM83D knockdown promoted colorectal cancer cell apoptosis, inhibited cell
proliferation, cell migration and invasion, which might be associated with
inhibiting the FBXW7/Notch1 signal pathway. Our findings indicated that FAM83D is
a promising molecular target for colorectal cancer treatment.
PMID- 28407576
TI - HOTAIR may regulate proliferation, apoptosis, migration and invasion of MCF-7
cells through regulating the P53/Akt/JNK signaling pathway.
AB - Breast cancer is a common malignancy, and it is the second leading cause of
cancer-related death among women worldwide. The pathogenesis of breast cancer is
poorly understood, leading to unsatisfactory efficacy of current anti-PC
therapies. The aim of this study is to investigate the role of LncRNA HOTAIR in
proliferation, apoptosis, migration and invasion of human breast cancer cell line
MCF-7. MCF-7 cells were cultured and transfected with HOTAIR siRNA, and the
proliferation rate of cells was determined using MTT and colony-forming assay;
moreover, the apoptosis as well as cell cycles were determined using annexin
V/propidium iodide staining methods and analyzed using flow cytometery;
furthermore, cell scratch and transwell assays have been performed to examine the
migration and invasion of MCF-7 cells; Next, cells were collected, and RT-qPCR as
well as western blotting assay were performed to examine the expression of P53,
MDM2, AKT, JNK, MMP-2 and MMP-9. We discovered that knockdown of HOTAIR induced
significant decrease in proliferation and increase in apoptosis of MCF-7 cells,
and the cell cycles of HOTAIR siRNA transfected cells have been arrested at G1
phase (p<0.01); moreover, knockdown of HOTAIR lead to marked decrease in the
migration and invasion ability of MCF-7 cells; finally, knockdown of HOTAIR
induced significant decrease in the expression of P53/Akt/JNK (p<0.01), and
significant increase in the expression of P53 in MCF-7 cells (p<0.01). In
conclusion, our results proved that HOTAIR may regulate proliferation, apoptosis,
migration and invasion of MCF-7 cells through regulating the P53/Akt/JNK
signaling pathway.
PMID- 28407577
TI - Diabetes associated with male reproductive system damages: Onset of presentation,
pathophysiological mechanisms and drug intervention.
AB - Diabetes mellitus (DM) is a major health problem that affects patients' quality
of life quality throughout the world due to its many complications. Reproductive
dysfunction is one of the major secondary complications in both diabetic animals
and human beings. Furthermore, DM has recently broken the age barrier and has
been heavily diagnosed in children and young persons of reproductive age. In the
past few years, many studies on DM in male reproductive functions in both
diabetic men and experimental diabetic animals have been published. It is
recognized that sustained hyperglycemia, which impairs reproductive function in
diabetic men, is at risk of developing. DM harmfully affects male reproductive
functions in multiple areas; these may include spermatogenesis, sperm maturation,
fertility capability, penile erection, and ejaculation. Traditional medicine and
folklore worldwide have used numerous medicinal plants to manage the diabetic
reproductive dysfunction because bioactive phyto-constituents are affluent in
many places. Unfortunately, the exact reasons for diabetic male reproductive
dysfunction are not completely understood and currently there are no treatments
in reproductive medicine specifically for such lesions. The aim of this review is
to summarize current research findings of DM on reproductive functions, to
elaborate the underlying mechanisms related to these diseases via in vivo and in
vitro studies, and to describe the ameliorative effects of medicinal plants or
their products. The review findings provide a systematic understanding of DM on
the reproductive functions and lay the theoretical foundation for developing the
direction of reproductive medicine.
PMID- 28407578
TI - A peek into the drug development scenario of endometriosis - A systematic review.
AB - PURPOSE AND OBJECTIVE: Endometriosis is a gynaecological disease that is
characterised by the presence of endometrium like tissue-epithelium and stroma
that develops outside the uterine cavity, which is responsible for pelvic pain
and infertility. Even though several medical therapies exist for the treatment of
endometriosis, each of the drug class has its own limitations such as cost of
treatment, side-effects and its short-term effect on the symptoms of
endometriosis. In this review, we have attempted to summarize the current status
and challenges of drug development for endometriosis. METHODS: A systematic
review was done and all the RCTs were selected from the identified hits. We
included studies that explored the usage of therapeutic drugs on endometriosis
patients from inception till November 2016. The search term used was
'Endometriosis' using PubMed and Clinicaltrials.gov. For the final analysis, 60
articles were analyzed and we identified the newly emerging drug therapies for
endometriosis treatment and have briefed their current status and challenges in
drug development for endometriosis. The quality of the selected studies was
assessed based on the degree of bias. RESULTS: The current classes of drugs that
have shown promising therapeutic results include Gonadotropin- releasing hormone
(GnRH) antagonists, aromatase inhibitors (AI), and selective progesterone and
estrogen receptor modulators, dopamine receptor-2-agonists and statins. The drugs
that failed midway during development include tanezumab, rosiglitazone,
infliximab, pentoxifylline, telapristone acetate, asoprisnil and raloxifene.
CONCLUSION: From the literature review, it appears that the most promising
molecules for the treatment of endometriosis in the near future include elagolix,
mifepristone, TAK-385, KLH-2109 and ASP1707 and cabergoline. It remains to be
seen if these molecules would succeed large phase 3 clinical trials and overcome
the regulatory hurdles to become an essential tool in the gynaecologist's
armamentarium against endometriosis.
PMID- 28407579
TI - PLGA-PEG nano-delivery system for epigenetic therapy.
AB - Efficient delivery of cytidine analogues such as Azacitidine (AZA) into solid
tumors constitutes a primary challenge in epigenetic therapies. We developed a di
block nano-vector based on poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene
glycol) (PEG) for stabilization of the conjugated AZA under physiological
conditions. With equimolar drug content, our nano-conjugate could elicit a better
anti-proliferative effect over free drug in breast cancer both in vitro and in
vivo, through reactivation of p21 and BRCA1 to restrict cell proliferation. In
addition, we applied single-molecule fluorescence tools to characterize the
intracellular behavior of the AZA-PLGE-PEG nano-micelles at a finer
spatiotemporal resolution. Our results suggest that the nano-micelles could
effectively enrich in cancer cells and may not be limited by nucleoside
transporters. Afterwards, the internalized nano-micelles exhibit pH-dependent
release and resistance to active efflux. Altogether, our work describes a
delivery strategy for DNA demethylating agents with nanoscale tunability,
providing a cost-effective option for pharmaceutics.
PMID- 28407580
TI - Isoalantolactone inhibits LPS-induced inflammation via NF-kappaB inactivation in
peritoneal macrophages and improves survival in sepsis.
AB - Sepsis, a clinical syndrome occurring in patients following infection or injury,
is a leading cause of mortality worldwide. It involves uncontrolled inflammatory
response resulting in multi-organ failure and even death. Isoalantolactone (IAL),
a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless,
little is known about the anti-inflammatory effects of IAL, and the role of IAL
in sepsis is unclear. In this study, we demonstrated that IAL decreased
lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG2 and cytokines
(IL-6, TNF-alpha) in peritoneal macrophages and RAW 264.7 macrophages. Moreover,
molecular mechanism studies indicated that IAL plays an anti-inflammatory role by
inhibiting LPS-induced activation of NF-kappaB pathway in peritoneal macrophages.
In vivo, IAL reduced the secretion of IL-6 and TNF-alpha in serum, and increased
the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated
the activation of NF-kappaB pathway in liver. Taken together, our data suggest
that IAL may represent a potentially new drug candidate for the treatment of
sepsis.
PMID- 28407581
TI - Current research scenario for microcystins biodegradation - A review on
fundamental knowledge, application prospects and challenges.
AB - Microcystins (MCs) are common cyanotoxins produced by harmful cyanobacterial
blooms (HCBs) and severely threaten human and ecosystems health. Biodegradation
is an efficient and sustainable biological strategy for MCs removal. Many novel
findings in fundamental knowledge and application potential of MC-biodegradation
have been documented. Little effort has devoted to summarize and comment recent
research progress on MC-biodegradation, and discuss the research problems and
gaps. This review deals with current research scenario in aerobic and anaerobic
biodegradation for MCs. Diverse organisms capable of degrading MCs are
encapsulated. Enzymatic mechanisms and influence factors regulating aerobic and
anaerobic MC-biodegradation are summarized and discussed, which are essential for
assessing and reducing MC-risks during HCBs episodes. Also, we propose some ideas
to solve the challenges and bottleneck problems in practical application of MC
biodegradation, and discuss research gaps and promising research methods which
deserve special attention. This review may provide new insights on future
direction of MC-biodegradation research, in order to further broaden its
application prospects for bioremediation.
PMID- 28407582
TI - Influence of sample matrix on the bioavailability of arsenic, cadmium and lead
during co-contaminant exposure.
AB - In this study, the influence of sample matrix on the relative bioavailability of
arsenic (As), cadmium (Cd) and lead (Pb) was assessed following exposure of
C57BL/6 mice to spiked aged (12years) soils. AIN93G mouse chow was amended with
individual and tertiary As, Cd and Pb soil combinations which were administered
to mice over a 9day exposure period. Contaminant relative bioavailability was
calculated by comparing As urinary excretion and Cd-kidney/Pb-liver accumulation
to corresponding values for compounds used to derive the respective toxicity
reference value. Strong linear dose-responses were observed for mice exposed to
AIN93G mouse chow augmented with individually spiked soil with As, Cd and Pb.
When mice were exposed to co-contaminants, As relative bioavailability (RBA)
decreased similar to results from previous co-contaminant salt experiments
presumably due to the influence of Cd on phosphate transport proteins, which are
utilized for As absorption. However, a decrease in Cd-kidney and Pb-liver
accumulation was also observed following co-co-exposure. It was postulated that
this resulted from interactions with other (essential) metals (e.g. iron,
aluminium, manganese, magnesium) within the soil matrix and their influence on
absorption via divalent metal transporters.
PMID- 28407583
TI - Photodebromination behaviors of polybrominated diphenyl ethers in methanol/water
systems: Mechanisms and predicting descriptors.
AB - This study investigated the photodebromination behaviors of polybrominated
diphenyl ethers (PBDEs) in methanol or methanol/water systems. The kinetics of
three sets of bromated diphenyl ether (BDE) isomers were compared in the same
reactors, and the results showed that the PBDE isomers with lower energy of
lowest unoccupied molecular orbital and higher energy of highest occupied
molecular orbital will be degraded faster by ultraviolet (UV) light than other
BDE isomers. The overall debromination pathways of 2,2',4,4'-tetrabromodiphenyl
ether (BDE-47) were elucidated, and we found that the bromine substituents with
higher Mulliken charges were preferentially removed. This demonstrated that
Mulliken charges can be used to predict the photodebromination pathways of PBDEs.
In methanol/water systems, when the ratio of methanol and water decreased, the
degradation rate of BDE-47 decreased, whereas that of diphenyl ether increased.
This phenomenon can be attributed to the mechanism of photodegradation of PBDEs
gradually shifting from the reductive debromination to the undebromination
process as the ratio of methanol and water decreases. The chromatogram of high
performance liquid chromatography and gas chromatography-mass spectrometry during
this process also verified this explanation. The debromination pathways of BDE-47
are consistent in methanol/water systems with different methanol to water ratios
and in different organic solvents.
PMID- 28407584
TI - Oxidative coupling of acetaminophen mediated by Fe3+-saturated montmorillonite.
AB - The wide usage of acetaminophen as human medicine has resulted in its ubiquitous
occurrence in various environmental compartments. However, the information for
the transformation of acetaminophen in soil is still limited. In this study,
oxidative coupling of acetaminophen in bulk solution mediated by Fe3+-saturated
montmorillonite was observed under different environmental conditions. In the
absence of natural phenolic acids, acetaminophen could be fully eliminated from
the solution within 72h at pH3.5, acetaminophen dimer was identified as the major
reaction product. Reduction of montmorillonite associated Fe3+ coupled with the
oxidation of acetaminophen was considered as the main mechanism for acetaminophen
transformation on Fe3+-saturated montmorillonite. The clay associated Fe3+ showed
higher reactivity than Fe3+ in solution due to the strong complexation between
surface Fe3+ and acetaminophen. The cross-coupling reaction between acetaminophen
and phenolic acids was also observed when phenolic acids were present in the
system. While with the increase of phenolic acid concentration, the competition
for the reactive sites between acetaminophen and phenolic acids significantly
suppressed acetaminophen removal. These results demonstrated the importance of
transition metal saturated clay minerals for the abiotic transformation of
anthropogenic micropollutants.
PMID- 28407585
TI - The influence of land urbanization on landslides: An empirical estimation based
on Chinese provincial panel data.
AB - This study used panel data for 28 provinces and municipalities in China from 2003
to 2014 to investigate the relationship between land urbanization and landslides
by building panel models for a national sample and subsamples from the three
regions of China and studied the problems of landslide prevention measures based
on the relationship. The results showed that 1) at the national level, the
percentage of built-up area and road density are respectively negative and
positive for landslides. 2) At the regional level, the improvement of landslide
prevention measures with increasing economic development only appears in built-up
areas. The percentage of built-up areas increases the number of landslides in the
western region and decreases the number in the central and eastern regions; the
degree of decrease in the eastern region is larger than in the central region.
Road density increases the number of landslides in each region, and the degree
increases gradually from the west to the east. 3) The effect of landslide
prevention funding is not obvious. Although the amount of landslide prevention
funds decreases the number of landslides at the national level, the degree of
increase is too small. Except in the central region, the amount of landslide
prevention funding did not decrease the number of landslides effectively in the
western and eastern regions. We propose a series of policy implications based on
these test results that may help to improve landslide prevention measures.
PMID- 28407586
TI - Physiological and biochemical impacts induced by mercury pollution and seawater
acidification in Hediste diversicolor.
AB - The present study evaluated the impacts of predicted seawater acidification and
Hg pollution, when stressors were acting alone and in combination, on the
polychaete Hediste diversicolor. Polychaetes were exposed during 28days to low pH
(7.5), Hg (5MUg/L) and pH7.5+Hg, and physiological alterations (respiration
rate), biochemical markers related to metabolic potential (glycogen and protein
content, electron transport system activity) and oxidative status (activity of
antioxidant and biotransformation enzymes, lipid peroxidation) were evaluated.
The results obtained clearly showed that polychaetes were sensitive to low pH and
Hg contamination, both acting alone or in combination. Organisms used their
energy reserves under stressful conditions, which decreased by up to half of the
control content, probably to fuel defence mechanisms. Our findings further
demonstrated that polychaetes exposed to these stressors presented increased
antioxidant defence mechanisms (3 fold compared to control). However, organisms
were not able to prevent cellular damage, especially noticed at Hg exposure and
pH7.5. Overall, although all the tested conditions induced oxidative stress in
Hediste diversicolor, the combined effect of seawater acidification and Hg
contamination did not induce higher impacts in polychaetes than single stressor
exposures. These findings may indicate that predicted climate change scenarios
may not increase Hediste diversicolor sensitivity towards Hg and may not
significantly change the toxicity of this contaminant to this polychaete species.
PMID- 28407587
TI - Removal of novel antiandrogens identified in biological effluents of domestic
wastewater by activated carbon.
AB - Environmental antiandrogenic (AA) contaminants in effluents from wastewater
treatment plants have the potential for negative impacts on wildlife and human
health. The aim of our study was to identify chemical contaminants with likely AA
activity in the biological effluents and evaluate the removal of these
antiandrogens (AAs) during advanced treatment comprising adsorption onto granular
activated carbon (GAC). In this study, profiling of AA contaminants in biological
effluents and tertiary effluents was conducted using effect-directed analysis
(EDA) including high performance liquid chromatography (HPLC) fractionation, a
recombinant yeast screen containing androgen receptor (YAS), in combination with
mass spectrometry analyses. Analysis of a wastewater secondary effluent from a
membrane bioreactor revealed complex profiles of AA activity comprising 14 HPLC
fractions and simpler profiles of GAC effluents with only 2 to 4 moderately polar
HPLC fractions depending on GAC treatment conditions. Gas chromatography-mass
spectrometry and ultra-high performance liquid chromatography-nanospray mass
spectrometry analyses of AA fractions in the secondary effluent resulted in
detection of over 10 chemical contaminants, which showed inhibition of YAS
activity and were potential AAs. The putative AAs included biocides, food
additives, flame retardants, pharmaceuticals and industrial contaminants. To our
knowledge, it is the first time that the AA properties of N-ethyl-2-isopropyl-5
methylcyclohexanecarboxamide (WS3), cetirizine, and oxcarbazepine are reported.
The EDA used in this study was proven to be a powerful tool to identify novel
chemical structures with AA activity in the complex aquatic environment. The
adsorption process to GAC of all the identified antiandrogens, except WS3 and
triclosan, fit well with the pseudo-second order kinetics models. Adsorption to
GAC could further remove most of the AAs identified in the biological effluents
with high efficiencies.
PMID- 28407588
TI - Multi-biomarker responses in fish (Jenynsia multidentata) to assess the impact of
pollution in rivers with mixtures of environmental contaminants.
PMID- 28407589
TI - Transport of anionic azo dyes from aqueous solution to gemini surfactant-modified
wheat bran: Synchrotron infrared, molecular interaction and adsorption studies.
AB - From the view of economic efficiency and technology sustainability, biomass
adsorbent has a high potential for pollution control. In the present study, the
performance of gemini 12-2-12 surfactant-modified wheat bran (MWB) for the
removal of anionic azo dyes from aqueous solution was investigated. A new insight
was gained into the modification mechanism through synchrotron-assisted infrared
analysis and molecular interaction simulation. The equilibrium and kinetic
studies for the adsorption of Acid Red 18 (AR-18), Acid Orange 7 (AO-7) and Acid
Black 1 (AB-1) on MWB were conducted. The Langmuir model well fit the adsorption
isotherm data. The adsorption kinetics could be described by the pseudo-second
order and intra-particle diffusion models. The results of thermodynamic studies
indicated the adsorption of AR-18 and AB-1 onto MWB was endothermic and
spontaneous, while the adsorption of AO-7 was exothermic. The optimum pH for the
adsorption of anionic azo dyes on MWB was 3. The adsorbed amount of anionic azo
dyes onto MWB decreased when NaCl concentration increased from 0 to 0.4molL-1.
The potential of modified wheat bran as a suitable adsorbent for the removal of
dyes from wastewater was presented in this study. The results can help understand
the migration patterns of organic pollutants at wheat bran-water interface.
PMID- 28407590
TI - Exposure to lethal levels of benzo[a]pyrene or cadmium trigger distinct protein
expression patterns in earthworms (Eisenia fetida).
AB - : Different pollutants induce distinct toxic responses in earthworms (Eisenia
fetida). Here, we used proteomics techniques to compare the responses of E.
fetida to exposure to the 10% lethal concentration (14d-LC10) of benzo[a]pyrene
(BaP) or cadmium (Cd) in natural red soil (China). BaP exposure markedly induced
the expression of oxidation-reduction proteins, whereas Cd exposure mainly
induced the expression of proteins involved in transcription- and translation
related processes. Furthermore, calmodulin-binding proteins were differentially
expressed upon exposure to different pollutants. The calcium (Ca2+)-binding
cytoskeletal element myosin was down-regulated upon BaP treatment, whereas the
Ca2+-binding cytoskeletal element tropomyosin-1 was up-regulated upon Cd
treatment. Some proteins exhibited opposite responses to the two pollutants. For
instance, catalase (CAT) and heat shock protein 70 were up-regulated upon BaP
treatment and down-regulated upon Cd treatment. A significant (p<0.05, one-way
ANOVA with least-significant difference (LSD) test) increase in the level of
reactive oxygen species (ROS) and CAT activity further showed that BaP mainly
induces oxidative stress. Real-time PCR analysis showed that mRNA expression
often did not correlate well with protein expression in earthworms subjected to
Cd or BaP treatment. In addition, the expression of the gene encoding the protein
metallothionein, which was not detected in the protein analysis, was induced upon
Cd treatment, but slightly reduced upon BaP treatment. Therefore, BaP and Cd have
distinct effects on the protein profile of E. Fetida with BaP markedly inducing
ROS activity, and Cd mainly triggering genotoxicity. CAPSULE SUMMARY: Distinct
patterns of protein expression are induced in earthworms upon exposure to
different pollutants; BaP markedly induces high levels of ROS, while Cd resultes
in genotoxicity.
PMID- 28407591
TI - Reduction of Cr(VI) in simulated groundwater by FeS-coated iron magnetic
nanoparticles.
AB - FeS-coated iron (Fe/FeS) magnetic nanoparticles were easily prepared,
characterized, and applied for Cr(VI) removal in simulated groundwater. TEM, XRD,
and BET characterization tests showed that FeS coating on the surface of Fe0
inhibited the aggregation of Fe0 and that Fe/FeS at a S/Fe molar ratio of 0.207
possessed a large surface area of 62.1m2/g. Increasing the S/Fe molar ratio from
0 to 0.138 decreased Cr(VI) removal by 42.8%, and a further increase to 0.207
enhanced Cr(VI) removal by 63% within 72h. Moreover, Fe/FeS inhibited the
leaching of Fe, reducing the toxicity of the particles. Mechanistic analysis
indicated that Fe0, Fe2+, and S2- were synergistically involved in the reduction
of Cr(VI) to nontoxic Cr(III), which further precipitated as (CrxFe1-x)(OH)3 and
Cr(III)-Fe-S. The process of Cr(VI) sorption by Fe/FeS (S/Fe=0.207) was fitted
well with a pseudo-second-order kinetic model, and the isotherm data were
simulated by Langmuir isotherm model with a maximum sorption capacity of 69.7mg/g
compared to 48.9mg/g for Fe0. Low pH and initial Cr(VI) concentration favored
Cr(VI) removal. Continuous fixed bed column studies showed that simulated
permeable reactive barriers (PRB) with Fe/FeS was considerably effective for in
situ removal of Cr(VI) from groundwater. This study demonstrated the high
potential of Fe/FeS for Cr(VI) immobilization in water, groundwater, and soil.
PMID- 28407592
TI - Different effects of bisphenol a and its halogenated derivatives on the
reproduction and development of Oryzias melastigma under environmentally relevant
doses.
AB - Bisphenol A (BPA) and its halogenated compounds (H-BPAs) are widely detected in
the environmental media and organisms. However, their toxicological effects,
especially chronic exposure at low doses, have not been fully compared. In this
study, the effects of BPA and H-BPAs on the reproduction and development of
Oryzias melastigma were systematically assessed and compared at various
developmental stages. BPA and its derivatives tetrabromobisphenol A (TBBPA) and
tetrachlorobisphenol A (TCBPA) elicited the acceleration of embryonic heartbeat.
BPA did not show any significant impact on the hatching time and rate of embryos.
In contrast, both TBBPA and TCBPA led to the delayed hatching and decreased
hatching rate. Accordingly, the expressions of hatching enzyme significantly
decreased upon exposure and TCBPA was found to be more toxic than TBBPA. The body
weight and gonadsomatic index (GSI) of the treated fish were relatively lower
than the control fish upon long-term (four months from larvae to adult) exposure
to BPA rather than H-BPAs. Slowed oocyte development occurred in the ovary, and
the estrogen level decreased after exposure to BPA rather than H-BPAs. In male
fish, no significant alteration was observed in the testis for all groups. The
concentration of testosterone significantly decreased upon exposure to BPA rather
than H-BPAs. The effects of these three chemicals on the estrogen-related gene
expressions were different under various developmental stages. Our study
indicated the importance of considering both the exposure stages and structure
activity relationship when assessing the eco-toxicological impact of pollutants.
PMID- 28407593
TI - Assessing the influence of ocean acidification to marine amphipods: A comparative
study.
AB - CO2 increases in the ocean may occur both by the capacity of CO2 exchanges with
its dissolved form between atmosphere and surface seawater as well by CO2 leaks
during the carbon capture and storage (CCS) process. The decrease in seawater pH
may result in a reduction in the concentration of both hydroxide and carbonate
(OH- and CO32-). The main aim of this work is to conduct an ecotoxicology
comparative survey using two amphipod species from Europe and Brazil exposed to
different acidification (CO2) scenarios. For it, an integrative approach based on
the weight of evidence was used for comparative proposes to identify the effects
on the amphipods association with the acidification and with the related mobility
of metals. The results demonstrate that the Ampelisca brevicornis species is more
sensitive to pH reductions than the Hyale youngi species. Furthermore, this study
has demonstrated that the CO2 enrichment in aquatic ecosystems would cause
changes on the mobility of certain metals (Zn, Cu and As). The results of
Principal Component Analysis (PCA) showed that the dissolved Zn in overlying
water was strongly correlated with the decrease in the pH and was associated with
increased toxicity of the sediment to the exposed organisms, mainly for the A.
brevicornis species from Spain. Nevertheless, similar results were found in
relation to the mortality of amphipods in low pH values for all sediment tested.
Concluding, it is highlighted the importance of comparative studies in different
types of environment and improve the understood of the risks associated with the
ocean acidification.
PMID- 28407594
TI - Trifluoromethyl arylamides with antileukemia effect and intracellular inhibitory
activity over serine/arginine-rich protein kinases (SRPKs).
AB - The serine/arginine-rich protein kinases (SRPKs) have frequently been found with
altered activity in a number of cancers, suggesting they could serve as potential
therapeutic targets in oncology. Here we describe the synthesis of a series of
twenty-two trifluoromethyl arylamides based on the known SRPKs inhibitor N-(2
(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and the
evaluation of their antileukemia effects. Some derivatives presented superior
cytotoxic effects against myeloid and lymphoid leukemia cell lines compared to
SRPIN340. In particular, compounds 24, 30, and 36 presented IC50 values ranging
between 6.0 and 35.7 MUM. In addition, these three compounds were able to trigger
apoptosis and autophagy, and to exhibit synergistic effects with the
chemotherapeutic agent vincristine. Furthermore, compound 30 was more efficient
than SRPIN340 in impairing the intracellular phosphorylation status of SR
proteins as well as the expression of MAP2K1, MAP2K2, VEGF, and RON oncogenic
isoforms. Therefore, novel compounds with increased intracellular effects against
SRPK activity were obtained, contributing to medicinal chemistry efforts towards
the development of new anticancer agents.
PMID- 28407595
TI - Proteo-lipobeads to encapsulate cytochrome c oxidase from Paracoccus
denitrificans.
AB - Proteo-lipobeads (PLBs) are investigated as cell-free model systems to
encapsulate membrane proteins such as ion channels and transporters. PLBs are
based on nickel nitrile tri-acetic acid (Ni-NTA)-functionalized agarose beads,
onto which membrane proteins (MP) are bound via histidine(his)-tag. Composite
beads thus obtained (subsequently called proteobeads) are dialyzed in the
presence of lipid micelles to form PLBs. As an example we employed cytochrome c
oxidase from P. denitrificans with a his-tag fused to the C-terminus of subunitI.
In this orientation the P side of CcO faces the outside of the PLB and hence
protons are released to the outer aqueous phase, when electron transfer is
initiated by light excitation of Ru complexes. Proton release kinetics was probed
by fluorescence microscopy using the pH-sensitive sensor molecule fluorescein
DHPE inserted into the lipid layer. In order to monitor the generation of
membrane potentials we performed a FLIPR assay on the CcO embedded in PLBs using
the FRET pair CC2-DMPE/DiSBAC2(3). The combined results show that PLBs can be
used as a model system designed to quantify the kinetic parameters of membrane
proteins. In addition, the FLIPR assay demonstrates the feasibility of PLBs for
high throughput screening applications.
PMID- 28407596
TI - Super-enhanced particle nucleation in styrene emulsion polymerization in the
presence of sodium styrene sulfonate.
AB - The styrene (St) emulsion polymerization using Aerosol MA80 as surfactant and in
the presence of sodium styrene sulfonate (NaSS) was studied. The effect of NaSS
content was assessed using MA80 concentrations below and at the critical micellar
concentration. It was found that at the higher NaSS and MA80 contents, the number
of particles (N) reaches a maximum of the order of 1017particles/cm3 water, a
huge value that has never been reported. In this work an explanation for this
super-enhanced particle nucleation phenomenon is proposed. Such hypothesis is
based on the role of St-NaSS oligomers formed in the aqueous phase and their
synergy with MA80 molecules to provide colloidal stability to the system. The
proposal seems to be consistent with the experimental data obtained for the
evolution of monomer conversion, N, particles size distribution and the wideness
of this latter as well as with a theoretical estimation of the N.
PMID- 28407597
TI - Layer-by-layer deposition on a heterogeneous surface: Effect of sorption kinetics
on the growth of polyelectrolyte multilayers.
AB - Surface functionalization by means of controlled deposition of charged polymers
or nanoparticles using the layer-by-layer (LbL) approach has been used to modify
mostly engineered materials with well-defined surface chemistry and morphology.
In this regard, natural and inhomogeneous interfaces have gained very little
attention. Furthermore, natural substrates are susceptible to alterations by
factors commonly used to control the growth of multilayers, such as pH,
temperature and ionic strength. Here, we study the impact of sorption kinetics of
a bilayer system (Poly(diallyldimethylammonium chloride) (PDDA) and Poly(sodium 4
styrenesulfonate) (PSS)) on a natural heterogeneous wood surface at neutral pH,
without salt addition, on the multilayer buildup. To overcome analytical
limitations we introduce a complementary approach based on UV reflectance
spectroscopy, atomic force microscopy (AFM) and zeta potential measurements.
Compared to immersion times used for ideal substrates, we found that a high
surface coverage requires relatively long immersion, approximately 30min, into
polyelectrolyte solutions, while a sufficient removal of polyelectrolyte excess
during the washing step, requires even longer, about 100min. Based on these
findings, we show that film growth can be controlled kinetically. Long immersion
times provide well-defined and regular multilayers. The obtained data points to
specific requirements to be considered when LbL treatments are applied to rough,
porous and heterogeneous surfaces, and thereby sets a basis for a successful
transfer of various surface functionalization approaches already shown on ideal
surfaces.
PMID- 28407598
TI - Eggshell waste as catalyst: A review.
AB - Agricultural wastes are some of the most emerging problems in food industries
because of their disposal cost. However, it is also an opportunity for the
bioeconomy society if new uses for these residual materials can be found.
Eggshells, considered a hazardous waste by UE regulations, are discarded,
amounting hundreds of thousands of tonnes worldwide. This egg processing waste is
a valuable source material, which can be used in different fields such as fodder
or fertilizer production. Additionally, this residue offers interesting
characteristics to be used in other applications, like its employment as an
environment-friendly catalyst. In the present review we provide a global view of
eggshell waste uses as catalyst in different processes. According to reviewed
researching works, a huge variety of added value products can be obtained by
using this catalyst which emphasised the interest of further investigations in
order to widen the possible uses of this cheap green catalyst.
PMID- 28407599
TI - A structured participatory method to support policy option analysis in a social
ecological system.
AB - In this study we demonstrate how to support policy option analysis for a
problematic Social-Ecological System (SES) with the help of stakeholder
participation. SES sustainability problems 1) are highly complex, 2) may lack
reliable data, 3) encompass conflicting interests and 4) may require
contradictory management interventions. Our approach uses a structured
participatory method combining the Driver-Pressure-State-Impact-Response (DPSIR)
model together with Fuzzy Cognitive Mapping (FCM) to capture the complexity of
the system and simplify its representation for simulation and policy option
analysis. Using this novel mixed-method was useful in dealing with above
mentioned characteristics of the complex SES problems. The method was applied in
a case study of water scarcity in Rafsanjan, Iran. FCMs were produced for 60
individual farmers and 40 individual researchers and policy makers. Our mixed
method analysis reveals similarities and differences of stakeholder knowledge and
problem perception, and simulates the impacts of alternative policy options
according to each group's perception. The final result of our case study
indicates that farmers in Rafsanjan strongly believe in the impact of economic
diversification on reducing water shortage, but they have a low level of trust in
the ability of the government to regulate and control water usage, whereas the
policy makers and researchers still believe in the role of government control and
monitoring policies to deal with water scarcity in Rafsanjan.
PMID- 28407600
TI - Efficacy of free and encapsulated Bacillus lichenformis strain SL10 on
degradation of phenol: A comparative study of degradation kinetics.
AB - The present study exemplifies phenol degradation efficacy of the free and
encapsulated bacterial isolate, explored the degradation kinetics and storage
stability in detail. In brief, isolation, identification and phenol degradation
potential of the bacterial made from wastewater treated sludge samples. The
organism identified as B. licheniformis demonstrates phenol degradation at a
concentration more than 1500 ppm. Optimization of environmental parameters
reduces the time taken for degradation considerably. The organism has further
been encapsulated using whey protein and the efficacy of encapsulated species
suggested that encapsulation protects the cells from high concentration of phenol
and at the same time expedite the degradation of the chosen pollutant at
appreciable level. The encapsulated species effectively degrade 3000 ppm
concentration of phenol within 96 h of incubation. Both pH and temperature
stability observed in the encapsulated species suggests the effectiveness of the
encapsulation. The encapsulated cells displayed storage stability for a four week
period at 4 C and reusability up to three exposures. Degradation effected through
intracellular catechol 2,3 dioxygenase. In conclusion, encapsulation of B.
licheniformis (i) protects the cells from direct exposure to toxic pollutants;
(ii) facilitates the field scale application and (iii) eliminate the practical
difficulties in handling wet biomass in field application and assures the best
possible way of remediating the phenol contaminated soil.
PMID- 28407601
TI - Changes in household food insecurity are related to changes in BMI and diet
quality among Michigan Head Start preschoolers in a sex-specific manner.
AB - Children living in households that have recently become food insecure may be
particularly vulnerable to adverse weight and dietary changes, but longitudinal
studies examining these associations are lacking. Using data from 501 Head Start
preschoolers from Michigan (48% male) who were followed during one school year as
a part of a randomized obesity prevention trial, we examined changes in
children's adiposity indices and dietary quality according to changes in
household food insecurity. Household food insecurity change status was
categorized as persistently food secure, became food secure, persistently food
insecure, or became food insecure. Linear mixed effects models were used to
estimate relative changes in BMI-for-age z scores (BAZ), triceps skinfolds-for
age z scores (TAZ), or diet quality (assessed with the 2010 Healthy Eating Index)
over the school year according to food insecurity category. We found that girls
from households that became food insecure over the year had a 0.21 unit higher
gain in BAZ than girls from households that were persistently food secure, after
adjustment for potential confounders (95% CI 0.02 to 0.39, P = 0.03). Girls from
households that became food secure had improvements in dietary quality over the
year compared to girls from persistently food insecure households (adjusted
difference in Healthy Eating Index score change = 9.1 points; 95% CI 3.0 to 15.0;
p = 0.003). There were no statistically significant associations with changes in
TAZ. Among boys, there were no associations between changes in household food
insecurity and changes in BAZ, TAZ, or dietary quality. In summary, we found that
BMI and diet quality changes of Head Start preschool girls were correlated with
short-term changes in household food insecurity. Continued research efforts
should focus on identifying the most effective ways to promote the health of
children in food insecure households, especially those who may have recently
transitioned or are transitioning into food insecurity.
PMID- 28407602
TI - Socio-psychological mediators of the relationship between behavioral health
stigma and psychiatric symptoms.
AB - The stigma associated with mental illness or addiction is significantly and
positively related to psychiatric symptoms. According to Modified Labeling
Theory, several processes should mediate this relationship, including rejection
experiences, stigma management (secrecy coping), and social support. In the first
comprehensive test of this theory, we examined a serial mediation model on three
waves of data from 138 adults receiving outpatient behavioral health treatment.
Participants were recruited from outpatient behavioral health clinics in a large
northeastern city in the United States and completed interviews that assessed
stigma, rejection experiences, stigma management, social support, and psychiatric
symptoms. There was a direct effect between stigma and psychiatric symptoms and
an indirect effect in which perceived rejection, secrecy coping and social
support sequentially and longitudinally intervened in the stigma and psychiatric
symptom relationship. Higher perceptions of stigma predicted more rejection
experiences, which marginally increased secrecy coping and decreased social
support. In turn, decreased social support increased psychiatric symptoms. We
provide support for Modified Labeling Theory and the clinical utility of specific
mediators in the relationship between stigma and psychiatric symptoms among
adults in behavioral health treatment living in urban settings.
PMID- 28407603
TI - Death of a salesman.
PMID- 28407604
TI - Plain packaging: a logical progression for tobacco control in one of the world's
'darkest markets'.
AB - The Australian approach to tobacco control has been a comprehensive one,
encompassing mass media campaigns, consumer information, taxation policy, access
for smokers to smoking cessation advice and pharmaceutical treatments, protection
from exposure to tobacco smoke and regulation of promotion. World-first
legislation to standardise the packaging of tobacco was a logical next step to
further reduce misleadingly reassuring promotion of a product known for the past
50 years to kill a high proportion of its long-term users. Similarly, refreshed,
larger pack warnings which started appearing on packs at the end of 2012 were a
logical progression of efforts to ensure that consumers are better informed about
the health risks associated with smoking. Regardless of the immediate effects of
legislation, further progress will continue to require a comprehensive approach
to maintain momentum and ensure that government efforts on one front are not
undermined by more vigorous efforts and greater investment by tobacco companies
elsewhere.
PMID- 28407605
TI - Standardised packaging and new enlarged graphic health warnings for tobacco
products in Australia-legislative requirements and implementation of the Tobacco
Plain Packaging Act 2011 and the Competition and Consumer (Tobacco) Information
Standard, 2011.
AB - This paper describes the development, content and implementation of two pieces of
Australian tobacco control legislation: one to standardise the packaging of
tobacco products and the other to introduce new, enlarged graphic health
warnings. It describes the process of legislative drafting, public consultation
and parliamentary consideration. It summarises exactly how tobacco products have
been required to look since late 2012. Finally, it describes implementation, most
particularly, the extent to which packs compliant with the legislation became
available to consumers over time.
PMID- 28407606
TI - Australian adult smokers' responses to plain packaging with larger graphic health
warnings 1 year after implementation: results from a national cross-sectional
tracking survey.
AB - BACKGROUND: We assessed whether the Australian plain packs with larger graphic
health warnings (GHWs) achieved three specific objectives of reducing the appeal
of tobacco, increasing health warning effectiveness and reducing the ability of
packaging to mislead about smoking harms. METHODS: We compared responses from
continuous cross-sectional telephone surveys of n=2176 cigarette smokers during
pre-plain packaging (April-September 2012, pre-PP) with n=759 surveyed in the
transition period (October-November 2012) and n=4240 during the first year of
implementation (December 2012-November 2013, PP year 1), using multivariate
logistic regression analyses. RESULTS: From pre-PP to PP year 1, more smokers
disliked their pack (p<0.001), perceived lower pack appeal (p<0.001), lower
cigarette quality (p<0.001), lower satisfaction (p<0.001) and lower value
(p<0.001) and disagreed brands differed in prestige (p=0.003). There was no
change in perceived differences in taste of different brands. More smokers
noticed GHWs (p<0.001), attributed much motivation to quit to GHWs (p<0.001),
avoided specific GHWs when purchasing (p<0.001), and covered packs (p<0.001),
with no change in perceived exaggeration of harms. PP year 1 saw an increased
proportion believing that brands do not differ in harmfulness (p=0.004), but no
change in the belief that variants do not differ in strength or the perceived
harmfulness of cigarettes compared with a year ago. Interactions signified
greater change for four outcomes assessing aspects of appeal among young adults
and two appeal outcomes among mid-aged adults. CONCLUSIONS: The specific
objectives of plain packaging were achieved and generally sustained among adult
smokers up to 12 months after implementation.
PMID- 28407608
TI - Short-term changes in quitting-related cognitions and behaviours after the
implementation of plain packaging with larger health warnings: findings from a
national cohort study with Australian adult smokers.
AB - BACKGROUND: Plain packaging (PP) with larger graphic health warnings (GHWs) was
implemented in Australia in late 2012. This study examined effects of these
packaging changes on short-term changes in quitting-related cognitions and
behaviours. METHODS: We used a series of cohorts of Australian adult cigarette
smokers originally sourced from a nationally representative cross-sectional
tracking survey, followed up approximately 1 month after their baseline interview
(n(weighted)=5441). Logistic regression analyses compared changes in seven
quitting-related outcomes over this 1-month follow-up period for the cohorts
surveyed before PP, over the period of transition to PP, and during the first
year of PP, adjusting for baseline levels of the outcome and covariates. RESULTS:
Compared to the referent group of smokers who completed their follow-up survey
pre-PP, those who were followed-up in the early transition period showed
significantly greater increases in rates of stopping themselves from smoking
(OR=1.51, 95% CI (1.08 to 2.10)) and higher quit attempt rates (OR=1.43, 95% CI
(1.00 to 2.03)), those followed-up in the late transition period showed greater
increases in intentions to quit (OR=1.42, 95% CI (1.06 to 1.92)) and pack
concealment (OR=1.55, 95% CI (1.05 to 2.31)), and those followed-up in the first
year of PP showed higher levels of pack concealment (OR=1.65, 95% CI (1.01 to
2.72)), more premature stubbing out of cigarettes (OR=1.55, 95% CI (1.01 to
2.36)), and higher quit attempt rates (OR=1.52, 95% CI (1.01 to 2.30)).
CONCLUSIONS: These findings provide some of the strongest evidence to date that
implementation of PP with larger GHWs was associated with increased rates of
quitting cognitions, microindicators of concern and quit attempts among adult
cigarette smokers.
PMID- 28407610
TI - Are quitting-related cognitions and behaviours predicted by proximal responses to
plain packaging with larger health warnings? Findings from a national cohort
study with Australian adult smokers.
AB - BACKGROUND: Implementation of tobacco plain packaging (PP) with larger graphic
health warnings (GHWs) in Australia had positive effects on responses reflecting
the specific objectives of the PP policy and on follow-up quitting-related
cognitions and behaviours. The aim of this study was to examine predictive
relationships between these proximal and distal outcomes. METHODS: A nationally
representative sample of Australian adult cigarette smokers completed a baseline
survey and a 1-month follow-up survey within the first year of policy
implementation (n(weighted)=3125). Logistic regression analyses tested whether
baseline measures of cigarette appeal, GHW effectiveness, perceived harm and
concern/enjoyment predicted each of seven follow-up measures of quitting-related
cognitions and behaviours, adjusting for baseline levels of the outcome and
covariates. RESULTS: In multivariable models, we found consistent evidence that
several baseline measures of GHW effectiveness positively and significantly
predicted the likelihood that smokers at follow-up reported thinking about
quitting at least daily, intending to quit, having a firm date to quit, stubbing
out cigarettes prematurely, stopping oneself from smoking and having attempted to
quit. Two of the quitting-related outcomes were also predicted by feeling more
smoking-related concern than enjoyment. A smaller number of the appeal variables
were prospectively associated with quitting-related outcomes, while believing
that brands do not differ in harmfulness did not positively predict any outcomes.
CONCLUSIONS: These findings provide an initial insight into the pathways through
which PP with larger GHWs may lead to changes in smoking behaviour. Future
research should examine whether the effects are conditional on individual
demographic and smoking characteristics.
PMID- 28407611
TI - Has the introduction of plain packaging with larger graphic health warnings
changed adolescents' perceptions of cigarette packs and brands?
AB - OBJECTIVE: To examine the impact of plain packaging of cigarettes with enhanced
graphic health warnings on adolescents' perceptions of pack image and perceived
brand differences. METHODS: Cross-sectional school-based surveys conducted in
2011 (prior to introduction of new cigarette packaging) and in 2013 (7-12 months
afterwards). Students aged 12-17 years (2011 n=6338; 2013 n=5915) indicated
whether they had seen a cigarette pack in previous 6 months. Students rated the
character of four popular cigarette brands, indicated level of agreement
regarding differences between brands in ease of smoking, quitting, addictiveness,
harmfulness and look of pack; and indicated positive and negative perceptions of
pack image. Changes in responses of students seeing cigarette packs in the
previous 6 months (2011: 60%; 2013: 65%) were examined. RESULTS: Positive
character ratings for each brand reduced significantly between 2011 and 2013.
Changes were found for four of five statements reflecting brand differences.
Significantly fewer students in 2013 than 2011 agreed that 'some brands have
better looking packs than others' (2011: 43%; 2013: 25%, p<0.001), with larger
decreases found among smokers (interaction p<0.001). Packs were rated less
positively and more negatively in 2013 than in 2011 (p<0.001). The decrease in
positive image ratings was greater among smokers. CONCLUSIONS: The introduction
of standardised packaging has reduced the appeal of cigarette packs. Further
research could determine if continued exposure to standardised packs creates more
uncertainty or disagreement regarding brand differences in ease of smoking and
quitting, perceived addictiveness and harms.
PMID- 28407612
TI - Do larger graphic health warnings on standardised cigarette packs increase
adolescents' cognitive processing of consumer health information and beliefs
about smoking-related harms?
AB - OBJECTIVE: To examine the impact of plain packaging of cigarettes with enhanced
graphic health warnings on Australian adolescents' cognitive processing of
warnings and awareness of different health consequences of smoking. METHODS:
Cross-sectional school-based surveys conducted in 2011 (prior to introduction of
standardised packaging, n=6338) and 2013 (7-12 months afterwards, n=5915).
Students indicated frequency of attending to, reading, thinking or talking about
warnings. Students viewed a list of diseases or health effects and were asked to
indicate whether each was caused by smoking. Two-'kidney and bladder cancer' and
'damages gums and teeth'-were new while the remainder had been promoted through
previous health warnings and/or television campaigns. The 60% of students seeing
a cigarette pack in previous 6 months in 2011 and 65% in 2013 form the sample for
analysis. Changes in responses over time are examined. RESULTS: Awareness that
smoking causes bladder cancer increased between 2011 and 2013 (p=0.002). There
was high agreement with statements reflecting health effects featured in previous
warnings or advertisements with little change over time. Exceptions to this were
increases in the proportion agreeing that smoking was a leading cause of death
(p<0.001) and causes blindness (p<0.001). The frequency of students reading,
attending to, thinking or talking about the health warnings on cigarette packs
did not change. CONCLUSIONS: Acknowledgement of negative health effects of
smoking among Australian adolescents remains high. Apart from increased awareness
of bladder cancer, new requirements for packaging and health warnings did not
increase adolescents' cognitive processing of warning information.
PMID- 28407613
TI - "You're made to feel like a dirty filthy smoker when you're not, cigar smoking is
another thing all together." Responses of Australian cigar and cigarillo smokers
to plain packaging.
AB - OBJECTIVE: To explore experiences of cigar and cigarillo smokers under Australian
laws requiring plain packaging (PP) and strengthened graphic health warnings
(GHWs). METHODS: In February/March 2014, we conducted: in-depth interviews with
10 regular premium cigar smokers; two focus groups with occasional premium cigar
and premium cigarillo smokers (n=14); four focus groups with non-premium
cigarillo smokers (n=28); and a national online survey of cigar and/or cigarillo
smokers (n=268). RESULTS: Premium cigar smokers had limited exposure to PP, with
many purchasing fully branded cigars in boxes duty free or online and singles in
non-compliant packaging. Those who were exposed noticed and were concerned by the
warnings, tried to avoid them and felt more like 'dirty smokers'. Changes in
perceived taste, harm and value were minimal for experienced premium cigar
smokers. Occasional premium cigar and premium cigarillo smokers with higher PP
exposure (gained by purchasing boxes rather than singles) perceived cigar/package
appeal and value had declined and noticed the GHWs. Non-premium cigarillo smokers
reported high PP exposure, reduced perceived appeal, quality, taste, enjoyment
and value, somewhat increased perceived harm, greater noticeability of GHWs and
concealment of packs and more contemplation of quitting. Online survey
participants reported increased noticeability of GHWs (33%), decreased appeal of
packaging (53%) and reduced consumption of cigars (42%) and cigarillos (44%)
since PP implementation. CONCLUSIONS: Non-premium cigarillo smokers appear to
have been most exposed and influenced by PP, with cigar smokers less so,
especially regular premium cigar smokers who have maintained access to fully
branded products.
PMID- 28407614
TI - Changes in use of types of tobacco products by pack sizes and price segments,
prices paid and consumption following the introduction of plain packaging in
Australia.
AB - OBJECTIVES: To describe changes among smokers in use of various types of tobacco
products, reported prices paid and cigarette consumption following the
standardisation of tobacco packaging in Australia. METHODS: National cross
sectional telephone surveys of adult smokers were conducted from April 2012 (6
months before transition to plain packaging (PP)) to March 2014 (15 months
afterwards). Multivariable logistic regression assessed changes in products,
brands and pack types/sizes; multivariable linear regression examined changes in
inflation-adjusted prices paid and reported cigarette consumption between the pre
PP and three subsequent periods-the transition phase, PP year 1 and PP post-tax
(post a 12.5% tax increase in December 2013). RESULTS: The proportion of current
smokers using roll-your-own (RYO) products fluctuated over the study period.
Proportions using value brands of factory-made (FM) cigarettes increased from pre
PP (21.4%) to PP year 1 (25.5%; p=0.002) and PP post-tax (27.8%; p<0.001).
Inflation-adjusted prices paid increased in the PP year 1 and PP post-tax phases;
the largest increases were among premium FM brands, the smallest among value
brands. Consumption did not change in PP year 1 among daily, regular or current
smokers or among smokers of brands in any market segment. Consumption among
regular smokers declined significantly in PP post-tax (mean=14.0, SE=0.33)
compared to PP year 1 (mean=14.8, SE=0.17; p=0.037). CONCLUSIONS: Introduction of
PP was associated with an increase in use of value brands, likely due to
increased numbers available and smaller increases in prices for value relative to
premium brands. Reported consumption declined following the December 2013 tax
increase.
PMID- 28407615
TI - Use of illicit tobacco following introduction of standardised packaging of
tobacco products in Australia: results from a national cross-sectional survey.
AB - OBJECTIVES: To assess whether following standardisation of tobacco packaging in
Australia, smokers were, as predicted by the tobacco industry, more likely to use
illicit tobacco. METHODS: National cross-sectional telephone surveys conducted
continuously from April 2012 (6 months before implementation of plain packaging
(PP)) to March 2014 (15 months after) using responses from current cigarette
smokers (n=8679). Changes between pre-PP, the transition to PP and PP phase were
examined using logistic regression models. RESULTS: Among those whose factory
made cigarettes were purchased in Australia, compared with pre-PP, there were no
significant increases in the PP phase in use of: 'cheap whites' (<0.1%; OR=0.24,
95% CI 0.04 to 1.56, p=0.134); international brands purchased for 20% or more
below the recommended retail price (0.2%; OR=3.49, 95% CI 0.66 to 18.35,
p=0.140); or packs purchased from informal sellers (<0.1%; OR=0.24, 95% CI 0.04
to 1.47, p=0.124). The prevalence of any use of unbranded illicit tobacco
remained at about 3% (adjusted OR=0.79, 95% CI 0.58 to 1.08, p=0.141).
CONCLUSIONS: While unable to quantify the total extent of use of illicit
manufactured cigarettes, in this large national survey we found no evidence in
Australia of increased use of two categories of manufactured cigarettes likely to
be contraband, no increase in purchase from informal sellers and no increased use
of unbranded illicit 'chop-chop' tobacco.
PMID- 28407616
TI - The advertised price of cigarette packs in retail outlets across Australia before
and after the implementation of plain packaging: a repeated measures
observational study.
AB - OBJECTIVE: This study monitored the advertised price of the most prominently
promoted and the cheapest single packs of cigarettes in Australian retail outlets
before and after the implementation of plain packaging. METHODS: A panel of 421
outlets in four large Australian cities was visited monthly from May 2012 to
August 2013 and the brand, pack size and price of the most-prominently listed and
lowest-priced single cigarette pack were recorded from each store's tobacco price
board. Changes in the inflation-adjusted stick price were examined using linear
mixed models, controlling for fixed effects of city, store type, area
socioeconomic status and random effects of time. The adjusted stick price was
also examined over time by tobacco manufacturer and pack size. RESULTS: The
inflation-adjusted stick price of the most-prominently advertised single packs
was significantly higher than in May-July 2012 from August-October 2012 for
mainstream and premium brands and from February-April 2013 for value brands.
Adjusted average stick prices of lowest-priced packs in August 2013 were $0.02
(95% CI $0.02 to $0.03, p<0.001) higher than in May-July 2012 ($Aug13). A large
real increase in stick price was seen in February-April 2013 across all major
manufacturers, market segments and pack size categories. DISCUSSION: The price of
cigarettes most prominently promoted on price boards did not decrease in the
months following implementation of Australia's plain packaging legislation.
Retail prices continued to increase above the level resulting from automatic
indexation of excise/customs duty even at the lowest-priced end of the Australian
market.
PMID- 28407617
TI - Did the recommended retail price of tobacco products fall in Australia following
the implementation of plain packaging?
AB - OBJECTIVES: This study aimed to assess the extent of any fall in recommended
retail prices (RRPs) of tobacco products sold in Australia following the 2012
implementation of plain packaging. METHODS: RRPs published in price lists by the
New South Wales Retail Tobacco Traders Association covering the months of
November 2011, November 2012 and November 2013 were recorded for all listed
brands and pack sizes. Average prices per stick were computed in 2013 dollars for
cigarette brands in each of 10 possible pack sizes, for each major tobacco
manufacturer, and across market segments. Average prices per gram in Australian
dollars adjusted to 2013 prices (AUD2013) were calculated for roll-your-own (RYO)
tobacco brands for each major manufacturer. RESULTS: Inflation-adjusted average
RRPs per stick in November 2013 were on average 6.4% higher than in November 2011
and 3.4% higher than in November 2012. The average RRP per gram of RYO products
in November 2013 was 10.2% and 5.4% higher than in November 2011 and November
2012, respectively. Within cigarette brands, the highest increases in RRP from
2011 to 2013 were seen among mainstream and premium brands (10.0% and 10.1%,
respectively) and among packs of 30s (18.3%) and 50s (12.5%). CONCLUSIONS: The
RRPs of tobacco products were higher in real terms 1 year after Australia's plain
packaging legislation was implemented. These increases exceeded increases
resulting from Consumer Price Index (CPI) indexation of duty and occurred across
all three major manufacturers for both factory made and RYO brands, all three
cigarette market segments and all major pack sizes.
PMID- 28407618
TI - Personal pack display and active smoking at outdoor cafe strips: assessing the
impact of plain packaging 1 year postimplementation.
AB - AIMS: We observed tobacco pack display and smoking at outdoor venues over three
summers to assess changes in their prevalence following Australia's introduction
of plain tobacco packaging with larger pictorial health warnings. METHODS:
Between January and April 2012 (preplain packaging (PP)), 2013 (early post-PP)
and 2014 (1 year post-PP), we counted patrons, smokers and tobacco packs at
cafes, restaurants and bars with outdoor seating. Pack type (branded, plain or
unknown) and orientation were noted. Rates of active smoking, pack display and
pack orientation were analysed using multilevel Poisson regression. RESULTS:
Prevalence of pack display among patrons declined from pre-PP (1 pack per 8.7
patrons) to early post-PP (1 pack per 10.4), and remained low 1 year post-PP (1
pack per 10.3). This appeared to be driven by a sustained decline in active
smoking post-PP (pre-PP: 8.4% of patrons were smoking; early post-PP: 6.4%; 1
year post-PP: 6.8%). Notably, active smoking declined more in venues with
children present than in those without. While early post-PP, plain packs were
less often displayed face-up (74.0%) and more often concealed (8.9%) than branded
packs pre-PP (face-up: 85.2%; concealed: 4.0%), this was not sustained 1 year
post-PP (face-up: 85.7%; concealed: 4.4%). Also, external case use increased from
pre-PP (1.2%) to early post-PP (3.5%), but returned to pre-PP levels 1 year post
PP (1.9%). CONCLUSIONS: This study demonstrated a sustained reduction in
visibility of tobacco products and smoking in public, particularly in the
presence of children, from pre-PP to 1 year post-PP. This effect is likely to
reduce smoking-related social norms, thereby weakening an important influence on
smoking uptake and better supporting quit attempts.
PMID- 28407619
TI - Did smokers shift from small mixed businesses to discount outlets following the
introduction of plain packaging in Australia? A national cross-sectional survey.
PMID- 28407620
TI - Outcome of allo simple limbal epithelial transplantation (alloSLET) in the early
stage of ocular chemical injury.
AB - PURPOSE: To analyse the outcome of allo simple limbal epithelial transplantation
(alloSLET) in eyes in the early stage following ocular chemical injury to achieve
rapid epithelialisation. PATIENTS AND METHODS: Records of 18 eyes of 17 patients
who underwent alloSLET between April 2013 and Jan 2016 were analysed
retrospectively. Patients with grade 4 or worse Dua's classification for chemical
injury, who presented within a month of the injury or with a non-healing
epithelial defect since the injury despite earlier medical or surgical
interventions, were included in the study. The time to epithelialisation was the
primary outcome measure and the best corrected visual acuity, the clinically
assessed epithelial phenotype and symblepharon formation were the secondary
outcome measures. RESULTS: The mean time to epithelialisation was noted to be
22.5+/-9.14 days. A best corrected visual acuity of better than 20/120 was
achieved in 13 eyes in a mean duration of 33.06+10.73 days following alloSLET.
Corneal phenotype with complete epithelialisation was achieved in the immediate
postoperative period in 17 of the 18 eyes (94.11%). Seven eyes had a gradual
failure of the allograft and 5 eyes underwent subsequent limbal autograft.
Symblepharon formation involving one to two quadrants was noted in 3 eyes
(16.7%). CONCLUSIONS: AlloSLET seems to be a useful technique to achieve rapid
epithelialisation in severe chemical injuries thereby preventing the adverse
effects of delayed epithelial healing. Visual rehabilitative procedures in the
chronic phase of chemical injury, in most instances following an alloSLET in the
acute stage, did not require keratoplasty, either lamellar or penetrating.
PMID- 28407621
TI - Potential Applications of Phyto-Derived Ceramides in Improving Epidermal Barrier
Function.
AB - The outer most layer of the skin, the stratum corneum, consists of corneocytes
which are coated by a cornified envelope and embedded in a lipid matrix of
ordered lamellar structure. It is responsible for the skin barrier function.
Ceramides (CERs) are the backbone of the intercellular lipid membranes. Skin
diseases such as atopic dermatitis and psoriasis and aged skin are characterized
by dysfunctional skin barrier and dryness which are associated with reduced
levels of CERs. Previously, the effectiveness of supplementation of synthetic and
animal-based CERs in replenishing the depleted natural skin CERs and restoring
the skin barrier function have been investigated. Recently, however, the barrier
function improving effect of plant-derived CERs has attracted much attention.
Phyto-derived CERs (phytoCERs) are preferable due to their assumed higher safety
as they are mostly isolated from dietary sources. The beneficial effects of
phytoCER-based oral dietary supplements for skin hydration and skin barrier
reinforcement have been indicated in several studies involving animal models as
well as human subjects. Ingestible dietary supplements containing phytoCERs are
also widely available on the market. Nonetheless, little effort has been made to
investigate the potential cosmetic applications of topically administered
phytoCERs. Therefore, summarizing the foregoing investigations and identifying
the gap in the scientific data on plant-derived CERs intended for skin-health
benefits are of paramount importance. In this review, an attempt is made to
synthesize the information available in the literature regarding the effects of
phytoCER-based oral dietary supplements on skin hydration and barrier function
with the underlying mechanisms.
PMID- 28407622
TI - Prolactin as a Potential Early Predictive Factor in Metastatic Non-Small Cell
Lung Cancer Patients Treated with Nivolumab.
AB - BACKGROUND/AIMS: Prolactin (PRL) is a peptide hormone and several studies have
demonstrated its role as a cytokine in human T cell-mediated immunity. We are
unaware if PRL is a positive or negative immunomodulator, but its effects on the
regulation of T cells could inhibit the antitumor activity elicited by nivolumab
(NIVO). We aimed to assess whether the occurrence of hyperprolactinemia in
metastatic non-small cell lung cancer (mNSCLC) patients treated with NIVO is
associated with poor clinical outcomes. METHODS: We evaluated 26 mNSCLC patients
treated with NIVO. Blood samples were collected in every patient to evaluate PRL
basal levels before starting the therapy with NIVO and before each following
administration of NIVO. All patients underwent a conventional CT to investigate
the effect of therapy according to Immune-related Response Evaluation Criteria in
Solid Tumors (IrRECIST). RESULTS: Twenty patients (77%) developed
hyperprolactinemia during the treatment, whereas 6 patients (23%) had stable
levels of PRL during the therapy (p = 0.001). A total of 95% of the 20 patients
with hyperprolactinemia had progressive disease (PD), according to CT results,
whereas only 2 patients (33%) out of 6 with stable PRL levels had PD (p = 0.004).
CONCLUSIONS: Hyperprolactinemia in mNSCLC patients treated with NIVO could
potentially represent a negative early predictive factor for poor clinical
outcomes, thus anticipating PD shown by CT scan.
PMID- 28407623
TI - Fine Needle Aspiration of Langerhans Cell Histiocytosis: A Cytopathologic Study
of 37 Cases.
AB - OBJECTIVE: Langerhans cell histiocytosis (LCH) is an uncommon neoplasm of
dendritic cells and predominantly occurs in children and young adults. The study
aims to evaluate cytopathologic features and current diagnostic concepts in a
large series of LCH on fine needle aspiration (FNA). STUDY DESIGN: We
retrospectively searched the pathology archives of The Johns Hopkins Hospital
(JHH) and Emory University Hospital (EUH) to identify all FNA cases diagnosed as
LCH in a period of 21 years. Cytologic material and immunohistochemical stains
were reviewed. RESULTS: A total of 37 LCH patients (26 from JHH and 11 from EUH)
with FNA diagnoses were identified. The sites of LCH included bone in 28, soft
tissue of head and neck in 6, and lymph nodes in 3. Thirty-one patients (84%)
were diagnosed as LCH, 4 (11%) had a descriptive diagnosis suggesting scant
cellularity with epithelioid/histiocyte-like cells and mixed inflammation, and 2
(5%) were non-diagnostic due to insufficient cellularity. Immunohistochemical
stains were performed on cell block sections in 26 cases, showing 24 of 24 (100%)
positive for CD1a, 22 of 23 (96%) positive for S100-protein, and 3 of 3 (100%)
positive for CD68. CONCLUSIONS: LCH can be accurately diagnosed in FNA based on
the characteristic cytomorphology and selected immunohistochemistry. Diagnosis
may be difficult in cases with scant or insufficient cellular material.
PMID- 28407624
TI - Risk of Malignancy and Risk of Neoplasia in the Bethesda Indeterminate
Categories: Study on 4,532 Thyroid Fine-Needle Aspirations from a Single
Institution in India.
AB - OBJECTIVES: To determine the frequency of category 3 (atypia of undetermined
significance [AUS]/follicular lesion of undetermined significance [FLUS]),
category 4 (follicular neoplasm), and category 5 (suspicious for malignancy) of
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), the risk of
malignancy (ROM) and the risk of neoplasia (RON) in these categories. STUDY
DESIGN: A retrospective 6-year audit of 4,532 thyroid fine-needle aspirations
(FNA) reported as per the TBSRTC from a single institution with cytohistological
correlation in 335 cases. RESULTS: The frequency of categories 3, 4, and 5 was
2.5, 3.9, and 0.5%, respectively; the upper and lower bound estimates of ROM
being 58.3, 23.6, 75% and 5.1, 5, and 12.5%, respectively. AUS/FLUS (n = 116)
cases were subcategorized as AUS, AUS-HC (Hurthle cell), AUS-PTC (AUS-papillary
thyroid carcinoma not excluded), FLUS, FLUS-FH (favor hyperplasia), FLUS-HC, and
FLUS-PTC. The AUS/FLUS malignancy ratio was 1:3.8. The sensitivity, specificity,
positive predictive value, negative predictive value, and diagnostic accuracy of
FNA thyroid was 80.5, 85.9, 80.7, 85.7, and 82.4%, respectively. CONCLUSION:
Implementation of TBSRTC aided in achieving internal quality control in reporting
thyroid FNA cytology. The AUS/FLUS frequency was 2.5%, which is at the lower
range of the recommended rate and was associated with a higher than recommended
upper bound estimate, but a comparable lower bound estimate of ROM.
PMID- 28407625
TI - Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design,
Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and
Reference Drugs.
AB - BACKGROUND/AIMS: Psoriasis plaque tests (PPTs) are important tools in the early
phases of antipsoriatic drug development. Two distinct PPT design variants (open
vs. occluded drug application) are commonly used, but no previous work has aimed
to directly compare and contrast their performance. METHODS: We compared the
antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported
in 2 separate studies, representing open and occluded PPT designs. The drug
effect size was measured by sonography (mean change in echo-poor band thickness),
chromametry, and standardized clinical assessment. RESULTS: Antipsoriatic effects
were detectable for the study drugs in both occluded and open PPTs. Differences
between the potency of antipsoriatic drugs and vehicle were observable. The total
antipsoriatic effect size appeared to be higher in the occluded PPT than the open
PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over
time revealed greater differences between some study drugs in the open PPT
compared to the occluded PPT. CONCLUSION: Taking the higher technical challenges
for the open PPT into account, we recommend the occluded PPT as a standard
screening setting in early drug development. In special cases, considering
certain drug aspects or study objectives that would require procedural
adaptations, an open PPT could be the better-suited design. Finally, both PPT
models show clear advantages: classification as phase I studies, small number of
psoriatic subjects, relatively short study duration, excellent discrimination
between compounds and concentrations, parallel measurement of treatment response,
and go/no go decisions very early in clinical development.
PMID- 28407626
TI - Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem
Cells by Increasing Vascular Endothelial Growth Factor Secretion in the
Ischemia/Reperfusion-Injured Heart.
AB - Adult stem cells have been studied as a promising therapeutic modality for the
functional restoration of the damaged heart. In the present study, a strategy for
enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using
micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a)
influences the secretion of vascular endothelial growth factor (VEGF) and
angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSCmiR
146a) decreased the expression of neurofibromin 2, an inhibitor of p21-activated
kinase-1 (PAK1). miR-146a also increased the expression of Ras-related C3
botulinum toxin substrate 1 and PAK1, which are known to induce VEGF expression,
and the formation of vascular branches was increased in hMSCmiR-146a compared to
hMSCs treated with VEGF. VEGF and p-Akt were increased in hMSCmiR-146a.
Furthermore, injection of hMSCmiR-146a after ischemia/reperfusion (I/R) injury
led to a reduction of fibrosis area and increased VEGF expression, confirming the
regenerative capacity such as reparative angiogenesis in the infarcted area.
Cardiac functions in I/R injury were improved following injection of hMSCmiR-146a
compared to the I/R group. Taken together, these data suggest that miR-146 is a
novel microRNA that regulates VEGF expression, and its use may be an effective
strategy for enhancing the therapeutic efficacy of hMSC transplantation into the
I/R-injured heart.
PMID- 28407627
TI - Determining Factors and Critical Periods in the Formation of Eating Habits:
Results from the Habeat Project.
AB - BACKGROUND: Eating habits form early during childhood and are likely to track
until the beginning of adulthood. Thus, understanding the formation of eating
habits is important. Consequently, the population targeted in the European
project Habeat comprised infants and young children up to 6 years of age.
SUMMARY: Habeat mainly focused on the qualitative dimension of eating habits with
a particular attention on vegetables and to a lesser extent on fruit. Food intake
of young children was also studied in 2 challenging situations where overeating
may occur and the relation between children's behaviour and feeding parental
practices was examined. Key Messages: Habeat found evidence that breastfeeding
may facilitate the consumption of vegetables and fruit and a greater variety of
healthy foods in later childhood. Introduction of a variety of vegetables at the
beginning of the complementary feeding period increases later acceptance of novel
foods. Repeated exposure is a powerful mechanism to increase children's intake of
a novel vegetable in infants and young children. Offering energy-dense snacks
before or after meals should be avoided. Moreover, food should be offered to
children in response to their feelings of hunger, and not used as reward for a
good behaviour or for any other reason.
PMID- 28407628
TI - Super-Selective Artery Embolization before Laparoscopic Partial Nephrectomy in
Treating Renal Angiomyolipoma.
AB - INTRODUCTION: To investigate the feasibility and efficiency of super-selective
artery embolization (SAE) before laparoscopic partial nephrectomy (LPN) in
treating renal angiomyolipoma (RAML). MATERIALS AND METHODS: A retrospective
analysis was conducted on 36 consecutive patients who underwent SAE before LPN
(group A, n = 16) or LPN directly (group B, n = 20) from June 2010 to March 2016.
Intraoperative blood loss, blood transfusion, operation time, warm ischemia time
(WIT), and prognosis were compared between groups. RESULTS: SAE before LPN
decreased operating time, intraoperative blood loss and WIT (p < 0.05), and
improved postoperative renal function (p < 0.001). Complications in group B
included intraoperative blood loss of 4 patients and postoperative hematuria of 2
patients who recovered a few days later. No complications were observed in group
A. In the follow-up of 3 months, a patient in group B formatted retroperitoneal
hematoma without any symptoms and received expectant treatment. CONCLUSIONS: The
application of SAE before LPN can decrease the difficulty of the surgery, the
complications, and the risk of rebleeding and RAMLs recurrence.
PMID- 28407630
TI - Characterization of the Tree Holes Used by Lepilemur ruficaudatus in the Dry,
Deciduous Forest of Kirindy Mitea National Park.
AB - Knowledge of the key resources for a species is critical for developing an
effective conservation strategy. Kirindy Mitea National Park is an important
refuge for the red-tailed sportive lemur (Lepilemur ruficaudatus), a nocturnal
folivorous lemur endemic to the dry deciduous forest of western Madagascar.
Because L. ruficaudatus sleeps in tree holes during the day, sleeping trees may
be an important resource for this species. Our goal was to characterize the
sleeping sites used by L. ruficaudatus at the Ankoatsifaka Research Station in
Kirindy Mitea National Park. In July and August 2012, tree characteristics were
recorded for 60 L. ruficaudatus sleeping sites. Intact and alive trees,
particularly Strychnos madagascariensis, were preferred by L. ruficaudatus.
Sleeping holes were generally located in taller trees (median hole height = 4 m)
and in trees with large girths (median = 20.5 cm). Greater protection from
predators and thermal shifts may be provided by intact trees and concealed tree
holes. Because tree characteristics can influence the presence and abundance of
forest-living primates, the availability and characteristics of particular trees
as potential sleeping shelters in a habitat must be taken into account in
conservation strategies for L. ruficaudatus.
PMID- 28407629
TI - Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate
Estimation in Older Adults in Contrast to beta-Trace Protein and beta2
Microglobulin.
AB - BACKGROUND: The glomerular filtration rate (GFR) is the most important measure of
kidney function and chronic kidney disease (CKD). This study aims to validate
commonly used equations for estimated GFR (eGFR) based on creatinine (cr),
cystatin C (cys), beta-trace protein (BTP), and beta2-microglobulin (B2M) in
older adults. METHOD: We conducted a validation study with 126 participants aged
between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54
mL/min/1.73 m2. The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI],
Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in
Renal Disease [MDRD]cr, Caucasian-Asian-Pediatric-Adult [CAPA]cys, Lund-Malmo
Revised [LM-REV]cr, and MEAN-LM-CAPAcr-cys), were assessed in terms of bias
(median difference: eGFR-mGFR), precision (interquartile range of the
differences), and accuracy (P30: percentage of estimates +/-30% of mGFR). The
equations were compared to a benchmark equation: CKD-EPIcr-cys. RESULTS: All
cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias
was mixed for the equations based only on creatinine. Accuracy was the highest
for CKD-EPIcr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m2
only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPIcr-cys
was not significantly more accurate than the other cystatin C-based equations. In
contrast, CKD-EPIcr-cys was significantly more accurate than all creatinine-based
equations except LM-REVcr. CONCLUSION: This study confirms that it is reasonable
to use equations incorporating cystatin C and creatinine in older patients across
a wide spectrum of GFR. However, the results call into question the use of
creatinine alone below mGFR 45 mL/min/1.73 m2. B2M and BTP do not demonstrate
additional value in eGFR determination in older adults.
PMID- 28407631
TI - A Longitudinal Study on Fetal Weight Estimation at Third Trimester of Pregnancy:
Comparison of Magnetic Resonance Imaging and 2-D Ultrasound Predictions.
AB - OBJECTIVE: To prospectively compare magnetic resonance (MR) estimation of fetal
weight (MR-EFW) performed at third trimester with ultrasound (US) estimation of
fetal weight (US-EFW) and actual birth weight, and to evaluate factors
influencing fetal growth rate near term. METHODS: US-EFW and MR-EFW were
calculated at a median of 33.0 and 37.7 weeks of gestation in 37 fetuses and
plotted on curve centiles to predict birth weights at 39.3 weeks of gestation.
The median absolute relative errors for predicted US-EFW and MR-EFW were
calculated. Regression analysis was used to investigate the effect of different
variables on fetal growth rate at 35.2 weeks of gestation. RESULTS: The relative
error of actual birth weight as predicted by US at 33.0 weeks was significantly
higher compared with MR (7.33 vs. 4.11%; p = 0.001). This was also the case for
fetal weight predicted by US at 37.7 weeks as compared with MR (6.63 vs. 2.60%; p
< 0.01). Fetal growth rate was significantly and independently positively
associated with the mother's weight and with gestational age at estimation (p <
0.05 for both variables). CONCLUSION: Fetal weight estimates predicted using MR
at third trimester are better than those given by prenatal US. Fetal growth rate
depends on fetal and maternal characteristics.
PMID- 28407632
TI - Hypothermic Neuronal Rescue from Infection-Sensitised Hypoxic-Ischaemic Brain
Injury Is Pathogen Dependent.
AB - Perinatal infection increases the vulnerability of the neonatal brain to hypoxic
ischaemic (HI) injury. Hypothermia treatment (HT) does not provide
neuroprotection after pre-insult inflammatory sensitisation by lipopolysaccharide
(LPS), a gram-negative bacterial wall constituent. However, early-onset sepsis in
term babies is caused by gram-positive species in more than 90% of cases, and
neuro-inflammatory responses triggered through the gram-negative route (Toll-like
receptor 4, TLR-4) are different from those induced through the gram-positive
route via TLR-2. Whether gram-positive septicaemia sensitises the neonatal brain
to hypoxia and inhibits the neuroprotective effect of HT is unknown. Seven-day
old Wistar rats (n = 178) were subjected to intraperitoneal injections of
PAM3CSK4 (1 mg/kg, a synthetic TLR-2 agonist) or vehicle (0.9% NaCl). After an 8
h delay, the left carotid artery was ligated followed by 50 min of hypoxia (8%
O2) at a rectal temperature of 36 degrees C. Pups received a 5-h treatment of
normothermia (NT, 37 degrees C) or HT (32 degrees C) immediately after the
insult. Brains were harvested after 7 days' survival for hemispheric and
hippocampal area loss analyses and immunolabelling of microglia (Iba1) and
hippocampal neurons (NeuN). Normothermic PAM3CSK4-injected animals showed
significantly more brain injury than vehicle animals (p = 0.014). Compared to NT,
HT significantly reduced injury in the PAM3CSK4-injected animals, with reduced
area loss (p < 0.001), reduced microglial activation (p = 0.006), and increased
neuronal rescue in the CA1 region (p < 0.001). Experimental induction of a sepsis
like condition through the gram-positive pathway sensitises the brain to HI
injury. HT was highly neuroprotective after the PAM3CSK4-triggered injury,
suggesting HT may be neuroprotective in the presence of a gram-positive
infection. These results are in strong contrast to LPS studies where HT is not
neuroprotective.
PMID- 28407633
TI - Psychosocial Factors and 30-Day Hospital Readmission among Individuals Receiving
Maintenance Dialysis: A Prospective Study.
AB - BACKGROUND: Thirty-day hospital readmissions are common among maintenance
dialysis patients. Prior studies have evaluated easily measurable readmission
risk factors such as comorbid conditions, laboratory results, and hospital
discharge day. We undertook this prospective study to investigate the
associations between hospital-assessed depression, health literacy, social
support, and self-rated health (separately) and 30-day hospital readmission among
dialysis patients. METHODS: Participants were recruited from the University of
North Carolina Hospitals, 2014-2016. Validated depression, health literacy,
social support, and self-rated health screening instruments were administered
during index hospitalizations. Multivariable logistic regression models with 30
day readmission as the dependent outcome were used to examine readmission risk
factors. RESULTS: Of the 154 participants, 58 (37.7%) had a 30-day hospital
readmission. In unadjusted analyses, individuals with positive screening for
depression, lower health literacy, and poorer social support were more likely to
have a 30-day readmission (vs. negative screening). Positive depression screening
and poorer social support remained significantly associated with 30-day
readmission in models adjusted for race, heart failure, admitting service,
weekend discharge day, and serum albumin: adjusted OR (95% CI) 2.33 (1.02-5.15)
for positive depressive symptoms and 2.57 (1.10-5.91) for poorer social support.
The area under the receiver operating characteristic curve (AUC) of the
multivariable model adjusted for social support status was significantly greater
than the AUC of the multivariable model without social support status (test for
equality; p value = 0.04). CONCLUSION: Poor social support and depressive
symptoms identified during hospitalizations may represent targetable readmission
risk factors among dialysis patients. Our findings suggest that hospital-based
assessments of select psychosocial factors may improve readmission risk
prediction.
PMID- 28407634
TI - Minimally Invasive Approach for Treatment of Seminal Vesicle Cyst Associated with
Ipsilateral Renal Agenesis.
AB - OBJECTIVES: We reviewed the clinical presentation and approach for the treatment
of symptomatic seminal vesicle cyst associated with ipsilateral renal agenesis
while presenting our experience with a series of 5 patients treated with
minimally invasive surgery for Zinner syndrome. MATERIALS AND METHODS: Between
the years 2008 and 2016, we operated on 5 patients who presented with symptomatic
seminal vesicle cyst and ipsilateral renal agenesis. Patients' charts and medical
records were reviewed and compared with past published minimally invasive series.
RESULTS: Four patients were treated in a laparoscopic approach and one was
treated with robotic-assisted seminal vesicle cyst excision. In all cases, the
cystic complex was drained and excised with marsupialization of the remaining
cyst walls to prevent cystic recurrence. The mean operating time was 3:47 h and
mean hospitalization time was 7 days (4-14). The mean follow-up period was 3.2
years (range 1.7-4.8 years). All patients reported a resolution of symptoms
during postoperative follow-up. CONCLUSIONS: Seminal vesicle cyst with
ipsilateral renal agenesis should be suspected in young male patients presenting
with pelvic cystic masses. Treatment is reserved for symptomatic patients and the
preferred approach is minimally invasive surgery. This approach is feasible and
effective while providing advantages both for the patient and the surgeon.
PMID- 28407635
TI - Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome
System in Auditory Cortex Senescence.
AB - BACKGROUND/AIMS: According to recent studies, central auditory impairments are
closely related to neurodegenerative diseases. However, the mechanism of central
presbycusis remains unclear. Ubiquitin C-terminal hydrolase L1 (UCHL1) is
important in maintaining proteasomal activity; however, the detailed mechanism
has not yet been fully elucidated. This study aims to investigate the molecular
alterations involved in UCHL1 regulation during auditory cortex aging. METHODS: D
Galactose (D-gal) induces oxidative stress and senescence in the auditory cortex,
as reported in our previous studies. Primary auditory cortex cells were treated
with D-gal for 72 h or 5 days. The proteins related to the ubiquitin proteasome
system (UPS) and proteasomal activities were evaluated. UCHL1 was overexpressed,
and the effects of UCHL1 on the UPS and proteasomal activity were analyzed.
RESULTS: Proteasomal activity was elevated at 72 h and decreased at 5 days in D
gal-treated primary auditory cortex cells. We also found that overexpression of
UCHL1 increased the UPS-related proteins UBE1, PSMA7, ubiquitinated proteins, and
monoubiquitin, and proteasomal activity. CONCLUSION: The results suggest that
UCHL1 may modify the aging process in the auditory cortex by regulating UPS-
related proteins.
PMID- 28407636
TI - Neuronal Regression of Internal Leg Vibroreceptor Organs in a Cave-Dwelling
Insect (Orthoptera: Rhaphidophoridae: Dolichopoda araneiformis).
AB - Animals' adaptations to cave habitats generally include elaboration of extraoptic
senses, and in insects the receptor structures located on the legs are supposed
to become more prominent in response to constant darkness. The receptors for
detecting substrate vibrations are often highly sensitive scolopidial sensilla
localized within the legs or the body. For troglobitic insects the evolutionary
changes in vibroreceptor organs have not been studied. Since rock is an extremely
unfavorable medium for vibration transmission, selection on vibration receptors
may be weakened in caves, and these sensory organs may undergo regressive
evolution. We investigated the anatomy of the most elaborate internal vibration
detection system in orthopteroid insects, the scolopidial subgenual organ complex
in the cave cricket Dolichopoda araneiformis (Orthoptera: Ensifera:
Rhaphidophoridae). This is a suitable model species which shows high levels of
adaptation to cave life in terms of both phenotypic and life cycle
characteristics. We compared our data with data on the anatomy and physiology of
the subgenual organ complex from the related troglophilic species Troglophilus
neglectus. In D. araneiformis, the subgenual organ complex contains three
scolopidial organs: the subgenual organ, the intermediate organ, and the
accessory organ. The presence of individual organs and their innervation pattern
are identical to those found in T. neglectus, while the subgenual organ and the
accessory organ of D. araneiformis contain about 50% fewer scolopidial sensilla
than in T. neglectus. This suggests neuronal regression of these organs in D.
araneiformis, which may reflect a relaxed selection pressure for vibration
detection in caves. At the same time, a high level of overall neuroanatomical
conservation of the intermediate organ in this species suggests persistence of
the selection pressure maintaining this particular organ. While regressive
evolution of chordotonal organs has been documented for insect auditory organs,
this study shows for the first time that internal vibroreceptors can also be
affected.
PMID- 28407638
TI - [Improvement of Stress Resistance and Quality of Life of Adults with Nervous
Restlessness after Treatment with a Passion Flower Dry Extract].
AB - BACKGROUND: The passion flower dried ethanolic extract investigated in this non
interventional study has well-documented calmative effects and good tolerability.
We investigated the effects of this extract on the stress resistance (resilience)
and quality of life (QoL) of patients suffering from nervous restlessness. The
addiction potential of the drug and the course of symptoms were also evaluated.
METHODS: Adult patients aged <= 95 years with the diagnosis 'nervous
restlessness' were treated for 12 weeks with a dried ethanolic extract of passion
flower (Passiflora incarnata L.). Standardized questionnaires were used to
evaluate the resilience (RS-13), QoL (EQ-5D including EQ-VAS), and the addiction
potential (BDEPQ). RESULTS: After 12 weeks of treatment, significant (p < 0.001)
improvements were measured in the patients' resilience (RS-13: from 52.1 to 67.7
points) and QoL (EQ-VAS: from 47.9 to 75.0 points). Also, the mean BDEPQ score
was significantly (p < 0.001) reduced (from 23.0 to 19.3 points). The mean values
of all accompanying symptoms (inner restlessness, sleep disturbance, exhaustion,
fear, lack of concentration, transpiration, nausea, trembling, and palpitation)
improved significantly (p < 0.001). Tolerability of treatment was rated as 'very
good' or 'good' by the majority of the patients. Three cases of mild adverse
events (tiredness) were reported. CONCLUSION: The passion flower extract
investigated in the present study appears to be effective in improving resilience
and QoL in patients suffering from nervous restlessness and is well tolerated.
PMID- 28407637
TI - Pneumatic Compression, But Not Exercise, Can Avoid Intradialytic Hypotension: A
Randomized Trial.
AB - BACKGROUND: Conventional hemodialysis (HD) is associated with dialysis-induced
hypotension (DIH) and ineffective phosphate removal. As the main source of
extracellular fluid removed during HD are the legs, we sought to reduce DIH and
increase phosphate removal by using cycling and pneumatic compression, which
would potentially provide higher venous return, preserving central blood flow and
also offering more phosphate to the dialyzer. METHODS: We evaluated 21 patients
in a randomized crossover fashion in which each patient underwent 3 different HD:
control; cycling exercise during the first 60 min; and pneumatic compression
during the first 60 min. Data obtained included bioelectrical impedance, hourly
blood pressure measurement, biochemical parameters, and direct quantification of
phosphate through the dialysate. DIH was defined as a drop in mean arterial
pressure (MAP) >=20 mm Hg. RESULTS: There was no difference in the
ultrafiltration rate (p = 0.628), delta weight (p = 0.415), delta of total, intra
and extracellular body water among the control, cycling, and pneumatic
compression (p = 0.209, p = 0.348, and p = 0.467 respectively). Delta MAP was
less changed by pneumatic compression when compared to control, cycling, and
pneumatic compression respectively (-4.7 [-17.2, 8.2], -4.7 [-20.5, -0.2], and
2.3 [-8.1, 9.0] mm Hg; p = 0.021). DIH occurred in 43, 38, and 24% of patients in
control, cycling, and pneumatic compression respectively (p = 0.014). Phosphate
removal did not increase in any intervention (p = 0.486). Higher phosphate
removal was dependent on ultrafiltration, pre dialysis serum phosphate, and
higher parathyroid hormone. CONCLUSION: Pneumatic compression during the first
hour of dialysis was associated with less DIH, albeit there was no effect on
fluid parameters. Neither exercise nor pneumatic compression increased phosphate
removal.
PMID- 28407639
TI - Modified Functional Superficial Parotidectomy With Ligation of the Major Branch
of the Parotid Duct Extending to the Superficial Lobe.
AB - A functional superficial parotidectomy can maintain salivary function by
preserving the Stensen duct. However, this technique still brings the possibility
of salivary leakage, because major branches of the parotid duct from the resected
site do not get ligated. To reduce this complication, this study introduces a
modified technique with major branch ligation. From December 2008 to February
2015, 14 patients who underwent superficial parotidectomy were divided into 2
groups. Group A was treated with the modified functional superficial
parotidectomy involving the major branch between the superficial lobe and parotid
duct. Group B was treated with the conventional superficial parotidectomy without
involving the major branch of the parotid duct. The clinical complications,
period of Hemovac usage, and surgical duration were noted in each group. Two of 8
patients in group A had a major branch from Stensen duct that was ligated, and
there was no evidence of salivary leakage or sialocele in any of the patients of
group A, whereas group B contained 2 cases of salivary leakage, one of which
became sialocele. Group A had a significantly longer Hemovac maintenance period
than group B (P < 0.05), and the duration of surgery was also significantly
different between the 2 groups (P < 0.05). Because a solitary major branch of the
main parotid duct occasionally extends toward the superficial lobe, our modified
technique-functional superficial parotidectomy with ligation of the major branch
toward the superficial lobe-is a useful option for treatment of a benign parotid
mass in such cases.
PMID- 28407640
TI - Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro
Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta
Analysis.
AB - Multidrug-resistant Neisseria gonorrhoeae infections have been declared 1 of the
top 3 urgent threats to public health. Approaches to combat resistance include
targeted therapy with antibiotics previously thought to be ineffective, made
possible by rapid molecular assays to predict susceptibility. Previous studies
have associated the gyrase A (gyrA) gene of N. gonorrhoeae with in vitro
resistance to ciprofloxacin. We conducted a systematic review of studies
comparing N. gonorrhoeae gyrA genotype results with conventional antimicrobial
susceptibility testing results. We identified 31 studies meeting inclusion
criteria, among which 7 different loci for mutations in the gyrA gene were
identified, from 16 countries between the years of 1996 and 2016. We then
performed a meta-analysis among those studies stratifying by use of real-time
polymerase chain reaction (PCR) or non-real-time PCR technique, and compared the
summary receiver operating characteristic curves between the 2 PCR methods. Among
studies using real-time PCR, the pooled estimate of sensitivity and specificity
of gyrA genotype results for the prediction of N. gonorrhoeae susceptibility to
ciprofloxacin were 98.2% (95% confidence interval [CI], 96.5-99.1%) and 98.6%
(95% CI, 97.0-99.3%), respectively. The summary operating characteristic curves
for studies using real-time PCR techniques were well separated from those using
non-real-time PCR techniques, with only slight overlap in the CIs, suggesting
that real-time PCR techniques were a more accurate approach. GyrA genotype
testing is a novel approach to combating the emergence of multidrug-resistant N.
gonorrhoeae and is a sensitive and specific method to predict in vitro
ciprofloxacin susceptibility.
PMID- 28407641
TI - Adverse Birth Outcomes and Maternal Neisseria gonorrhoeae Infection: A Population
Based Cohort Study in Washington State.
AB - BACKGROUND: Neisseria gonorrhoeae (gonorrhea) remains an important cause of
reproductive and obstetric complications. There has been limited population-based
research to evaluate the association between maternal gonorrhea and adverse birth
outcomes. METHODS: A population-based retrospective cohort study was conducted of
women with singleton pregnancies in Washington State from 2003 to 2014 using
linked birth certificate and birth hospitalization discharge data. The exposed
cohort consisted of women with gonorrhea diagnosed during pregnancy. The
unexposed group, defined as pregnant women without gonorrhea, was selected by
frequency-matching by birth year in a 4:1 ratio. Logistic regression was used to
determine crude and adjusted odds ratios (OR) for the association of maternal
gonorrhea and adverse birth outcomes. RESULTS: Women with gonorrhea during
pregnancy (N = 819) were more likely to be younger, black, single, less educated,
multiparous, and smokers compared with women without gonorrhea (N = 3276).
Maternal gonorrhea was significantly associated with a 40% increased odds
(adjusted OR, 1.4; 95% confidence interval [CI], 1.0-1.8) of low birth weight
infants compared with women without gonorrhea when adjusted for marital and
smoking status. Maternal gonorrhea was associated with a 60% increased odds (OR,
1.6; 95% CI, 1.3-2.0) of small for gestational age infants compared with women
without gonorrhea. CONCLUSIONS: This analysis showed that pregnant women with
gonorrhea were more likely to have low birth weight infants, consistent with
prior literature, and provided new evidence that maternal gonorrhea is associated
with small for gestational age infants. These findings support increased public
health efforts to prevent, identify, and treat gonorrhea infection during
pregnancy.
PMID- 28407642
TI - The Case for Extragenital Screening of Chlamydia trachomatis and Neisseria
gonorrhoeae in the College Health Setting.
AB - BACKGROUND: Although the Centers for Disease Control and Prevention does not
recommend routine oropharyngeal and anorectal screening for Chlamydia trachomatis
and Neisseria gonorrhoeae in the general population, they do recommend it for men
who have sex with men. However, risk-based extragenital screening of men may not
have been adopted at all college health centers, and existing research has not
focused on the college population. METHODS: We examined health records of men at
a college health center in a large urban university over 6 years to evaluate
effectiveness of C. trachomatis and N. gonorrhoeae screening. We also evaluated
the proportion of C. trachomatis and N. gonorrhoeae infections that would have
been missed if risk-based extragenital screening were not performed. Decisions to
screen at extragenital sites were based on patient-reported risk behavior.
RESULTS: For 4093 male college students screened, 7.6% of the screening visits
used extragenital screening in response to self-reported risk behaviors. The case
positivity rate for C. trachomatis was 3.1% with urogenital-only screening and
3.7% with risk-prompted extragenital screening. The case positivity rate for N.
gonorrhoeae was 0.7% with urogenital-only screening and 3.3% with risk-prompted
extragenital screening. If the college health center had relied solely on
urogenital screening rather than risk-based extragenital screening, 26.4% of C.
trachomatis infections and 63.2% of N. gonorrhoeae infections would have been
missed. CONCLUSIONS: One out of four C. trachomatis infections and 2 of 3 N.
gonorrhoeae infections would have been missed without extragenital screening in
this analysis of college men. This study reinforces Centers for Disease Control
and Prevention recommendations for risk-based extragenital screening and is the
first report to focus on college men. Because guidelines exist only for men,
future studies should focus on extragenital screening in college women to build
evidence for another group of patients that may benefit from this practice, given
the high risk in young adults.
PMID- 28407643
TI - The Use of Mathematical Models of Chlamydia Transmission to Address Public Health
Policy Questions: A Systematic Review.
AB - BACKGROUND: Mathematical models of chlamydia transmission can help inform disease
control policy decisions when direct empirical evaluation of alternatives is
impractical. We reviewed published chlamydia models to understand the range of
approaches used for policy analyses and how the studies have responded to
developments in the field. METHODS: We performed a literature review by searching
Medline and Google Scholar (up to October 2015) to identify publications
describing dynamic chlamydia transmission models used to address public health
policy questions. We extracted information on modeling methodology,
interventions, and key findings. RESULTS: We identified 47 publications
(including two model comparison studies), which reported collectively on 29
distinct mathematical models. Nine models were individual-based, and 20 were
deterministic compartmental models. The earliest studies evaluated the benefits
of national-level screening programs and predicted potentially large benefits
from increased screening. Subsequent trials and further modeling analyses
suggested the impact might have been overestimated. Partner notification has been
increasingly evaluated in mathematical modeling, whereas behavioral interventions
have received relatively limited attention. CONCLUSIONS: Our review provides an
overview of chlamydia transmission models and gives a perspective on how
mathematical modeling has responded to increasing empirical evidence and
addressed policy questions related to prevention of chlamydia infection and
sequelae.
PMID- 28407644
TI - Mobile Phone and Internet Use Mostly for Sex-Seeking and Associations With
Sexually Transmitted Infections and Sample Characteristics Among Black/African
American and Hispanic/Latino Men Who Have Sex With Men in 3 US Cities.
AB - BACKGROUND: Men who have sex with men (MSM) have a relatively high prevalence of
sexually transmitted infections (STIs). This study examines the association of
self-reported STIs and use of mobile phones and/or computer-based Internet to
meet sexual partners among black and Hispanic/Latino MSM in the United States.
METHODS: Black and Hispanic/Latino MSM (N = 853) were recruited from 3 US cities
(Chicago, IL; Kansas City, MO; and Fort Lauderdale, FL) via online and community
outreach. Men completed a computer-assisted, self-interview assessment on
demographics, use of mobile phones and computer-based Internet for sex-seeking,
sexual risk behavior, and self-reported bacterial STIs in the past year.
Multivariable logistic regression was used to model independent associations of
STIs and use of these technologies to meet sexual partners. RESULTS: Twenty-three
percent of the sample reported having an STI in the past year; 29% reported using
a mobile phone and 28% a computer-based Internet mostly for sex-seeking; and 22%
reported using both. Number of male sexual partners (past year) was associated
with any STI (adjusted odds ratio, 1.03; 95% confidence interval, 1.01-1.06).
Adjusting for human immunodeficiency virus status, number of male sexual partners
(past year), and demographic variables, men who reported use of both mobile
phones and computer-based Internet for sex-seeking had increased odds of
reporting an STI (adjusted odds ratio, 2.59; 95% confidence interval, 1.75-3.83),
as well as with separate reports of chlamydia, gonorrhea, and syphilis (P's <
0.05). CONCLUSIONS: Enhanced community education regarding STI prevention,
testing, and treatment options are necessary among this subpopulation of MSM who
may benefit from messaging via Internet and mobile phone application sites.
PMID- 28407645
TI - Designing Human Immunodeficiency Virus Counselling and Testing Services to
Maximize Uptake Among High School Learners in South Africa: What Matters?
AB - BACKGROUND: Increasing human immunodeficiency virus (HIV) testing in South Africa
is vital for the HIV response. Targeting young people is important as they become
sexually active and because HIV risk rapidly increases as youth enter their 20s.
This study aims to increase the understanding of high school learners'
preferences regarding the characteristics of HIV testing service delivery models
and to inform policy makers and implementers regarding potential barriers to and
facilitators of HIV testing. METHODS: An attitudinal survey was used to examine
HIV testing preferences among 248 high school learners in KwaZulu-Natal.
Statistical tests were used to identify the most favored characteristics of
testing service delivery models and examine key differences in preferences based
on demographic characteristics and testing history. RESULTS: Most learners were
found to prefer testing offered at a clinic on a Saturday (43%), using a finger
prick test (59%), conducted by a doctor (61%) who also provides individual
counselling (60%). Shorter testing times were preferred, as well as a monetary
incentive to cover any associated expenses. Time, location, the type of test, and
who conducts the test were most important. However, stratified analysis suggests
that preferences diverge, particularly around gender, grade, but also sexual
history and previous testing experience. CONCLUSIONS: Human immunodeficiency
virus testing services can be improved in line with preferences, but there is no
single optimal design that caters to the preferences of all learners. It is
unlikely that a "one-size-fits-all" approach will be effective to reach HIV
testing targets. A range of options may be required to maximize coverage.
PMID- 28407647
TI - Syphilis Masquerading As Mass Lesions: The Utility of Modern-Day Imaging and
Molecular Sequencing in Clinical Diagnosis.
AB - Syphilis has been known to present in a myriad of symptoms throughout the ages,
and until this day, the diagnosis remains elusive to the modern physician. We
present 2 unusual cases of syphilis that posed diagnostic challenges even in the
current era of new and advancing diagnostic tests.
PMID- 28407646
TI - Assessing the Performance of 3 Human Immunodeficiency Virus Incidence Risk Scores
in a Cohort of Black and White Men Who Have Sex With Men in the South.
AB - BACKGROUND: Risk scores have been developed to identify men at high risk of human
immunodeficiency virus (HIV) seroconversion. These scores can be used to more
efficiently allocate public health prevention resources, such as pre-exposure
prophylaxis. However, the published scores were developed with data sets that
comprise predominantly white men who have sex with men (MSM) collected several
years prior and recruited from a limited geographic area. Thus, it is unclear how
well these scores perform in men of different races or ethnicities or men in
different geographic regions. METHODS: We assessed the predictive ability of 3
published scores to predict HIV seroconversion in a cohort of black and white MSM
in Atlanta, GA. Questionnaire data from the baseline study visit were used to
derive individual scores for each participant. We assessed the discriminatory
ability of each risk score to predict HIV seroconversion over 2 years of follow
up. RESULTS: The predictive ability of each score was low among all MSM and lower
among black men compared to white men. Each score had lower sensitivity to
predict seroconversion among black MSM compared to white MSM and low area under
the curve values for the receiver operating characteristic curve indicating poor
discriminatory ability. CONCLUSIONS: Reliance on the currently available risk
scores will result in misclassification of high proportions of MSM, especially
black MSM, in terms of HIV risk, leading to missed opportunities for HIV
prevention services.
PMID- 28407648
TI - International Sexual Partnerships May Be Shaped by Sexual Histories and
Socioeconomic Status.
AB - Exchange sex and higher education were associated with an increased likelihood of
international sexual partnerships (ISPs). Exchange sex and older age were
associated with an increased likelihood of condomless sex in ISPs. Educational
and socioeconomic factors may create unbalanced power dynamics that influence
exchange sex and condomless sex in ISPs.
PMID- 28407649
TI - Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration:
An Emerging Clinical Presentation?
AB - These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b
presenting initially with edema and persistent painful ulceration illustrate that
clinical manifestations of LGV in the current outbreak in men who have sex with
men reflect the influence of both the serovars virulence and the host immune
system and are not confined to proctitis. L2b serovar could have a particular
high virulence profile, and the need for awareness of LGV as a cause of genital
ulceration is crucial.
PMID- 28407650
TI - Insurance Coverage and Utilization at a Sexually Transmitted Disease Clinic in a
Medicaid Expansion State.
AB - BACKGROUND: In Rhode Island, the Patient Protection and Affordable Care Act has
led to over 95% of the state's population being insured. We evaluated insurance
coverage and barriers to insurance use among patients presenting for services at
the Rhode Island sexually transmitted disease (STD) clinic. METHODS: We analyzed
factors associated with insurance coverage and utilization among patients
presenting for STD services between July and December 2015. RESULTS: A total of
692 patients had insurance information available; of those, 40% were uninsured.
Patients without insurance were more likely than those with insurance to be
nonwhite (50% among uninsured, compared with 40% among insured; P = 0.014) and
Hispanic or Latino/a (25%, compared with 16%; P = 0.006), and less likely to be
men who have sex with men (27%, compared with 39%; P = 0.001). Of those with
health insurance, 26% obtained coverage as a result of the Affordable Care Act,
and 56% of those were previously uninsured. Among uninsured individuals, barriers
to obtaining health insurance included cost and unemployment. Among those with
insurance, 43% reported willingness to use insurance for STD services. Barriers
to insurance use included concerns about anonymity and out-of-pocket costs.
CONCLUSIONS: Despite expanded insurance access, many individuals presenting to
the Rhode Island STD Clinic were uninsured. Among those who were insured,
significant barriers still existed to using insurance. STD clinics continue to
play an important role in providing safety-net STD services in states with low
uninsured rates. Both public and private insurers are needed to address financial
barriers and optimize payment structures for services.
PMID- 28407651
TI - Microscopy and Culture for the Diagnosis of Gonorrhea Methodological Issues on
Validity and Reliability.
PMID- 28407652
TI - Smartphone-Enabled Heart Rate Variability and Acute Mountain Sickness.
AB - INTRODUCTION: The autonomic system and sympathetic activation appears integral in
the pathogenesis of acute mountain sickness (AMS) at high altitude (HA), yet a
link between heart rate variability (HRV) and AMS has not been convincingly
shown. In this study we investigated the utility of the smartphone-derived HRV
score to predict and diagnose AMS at HA. METHODS: Twenty-one healthy adults were
investigated at baseline at 1400 m and over 10 days during a trek to 5140 m. HRV
was recorded using the ithlete HRV device. RESULTS: Acute mountain sickness
occurred in 11 subjects (52.4%) at >2650 m. HRV inversely correlated with AMS
Scores (r = -0.26; 95% CI, -0.38 to -0.13: P < 0.001). HRV significantly fell at
3700, 4100, and 5140 m versus low altitude. HRV scores were lower in those with
both mild (69.7 +/- 14.0) and severe AMS (67.1 +/- 13.1) versus those without AMS
(77.5 +/- 13.1; effect size n = 0.043: P = 0.007). The HRV score was weakly
predictive of severe AMS (AUC 0.74; 95% CI, 0.58-0.89: P = 0.006). The change
(delta) in the HRV Score (compared with baseline at 1400 m) was a moderate
diagnostic marker of severe AMS (AUC 0.80; 95% CI, 0.70-0.90; P = 0.0004). A fall
in the HRV score of >5 had a sensitivity of 83% and specificity of 60% to
identify severe AMS (likelihood ratio 1.9). Baseline HRV at 1400 m was not
predictive of either AMS at higher altitudes. CONCLUSIONS: The ithlete HRV score
can be used to help in the identification of severe AMS; however, a baseline
score is not predictive of future AMS development at HA.
PMID- 28407653
TI - Differential pattern of HIF-1alpha expression in HNSCC cancer stem cells after
carbon ion or photon irradiation: one molecular explanation of the oxygen effect.
AB - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) are resistant to
standard treatments, partly due to cancer stem cells (CSCs) localised in hypoxic
niches. Compared to X-rays, carbon ion irradiation relies on better ballistic
properties, higher relative biological effectiveness and the absence of oxygen
effect. Hypoxia-inducible factor-1alpha (HIF-1alpha) is involved in the
resistance to photons, whereas its role in response to carbon ions remains
unclear. METHODS: Two HNSCC cell lines and their CSC sub-population were studied
in response to photons or carbon ion irradiation, in normoxia or hypoxia, after
inhibition or not of HIF-1alpha. RESULTS: Under hypoxia, compared to non-CSCs,
HIF-1alpha is expressed earlier in CSCs. A combined effect photons/hypoxia, less
observed with carbon ions, results in a synergic and earlier HIF-1alpha
expression in both subpopulations. The diffuse ROS production by photons is
concomitant with HIF-1alpha expression and essential to its activation. There is
no oxygen effect in response to carbon ions and the ROS localised in the track
might be insufficient to stabilise HIF-1alpha. Finally, in hypoxia, cells were
sensitised to both types of radiations after HIF-1alpha inhibition. CONCLUSIONS:
Hypoxia-inducible factor-1alpha plays a main role in the response of CSCs and non
CSCs to carbon ion and photon irradiations, which makes the HIF-1alpha targeting
an attractive therapeutic challenge.
PMID- 28407654
TI - EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound
Elastography, Update 2017 (Short Version).
AB - We present here the first update of the 2013 EFSUMB (European Federation of
Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations
on the clinical use of elastography with a focus on the assessment of diffuse
liver disease. The short version provides clinical information about the
practical use of elastography equipment and interpretation of results in the
assessment of diffuse liver disease and analyzes the main findings based on
published studies, stressing the evidence from meta-analyses. The role of
elastography in different etiologies of liver disease and in several clinical
scenarios is also discussed. All of the recommendations are judged with regard to
their evidence-based strength according to the Oxford Centre for Evidence-Based
Medicine Levels of Evidence. This updated document is intended to act as a
reference and to provide a practical guide for both beginners and advanced
clinical users.
PMID- 28407655
TI - EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound
Elastography, Update 2017 (Long Version).
AB - We present here the first update of the 2013 EFSUMB (European Federation of
Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations
on the clinical use of elastography, focused on the assessment of diffuse liver
disease. The first part (long version) of these Guidelines and Recommendations
deals with the basic principles of elastography and provides an update of how the
technology has changed. The practical advantages and disadvantages associated
with each of the techniques are described, and guidance is provided regarding
optimization of scanning technique, image display, image interpretation,
reporting of data and some of the known image artefacts. The second part provides
clinical information about the practical use of elastography equipment and the
interpretation of results in the assessment of diffuse liver disease and analyzes
the main findings based on published studies, stressing the evidence from meta
analyses. The role of elastography in different etiologies of liver disease and
in several clinical scenarios is also discussed. All of the recommendations are
judged with regard to their evidence-based strength according to the Oxford
Centre for Evidence-Based Medicine Levels of Evidence. This updated document is
intended to act as a reference and to provide a practical guide for both
beginners and advanced clinical users.
PMID- 28407656
TI - High Blood Pressure during Pregnancy is not a Protective Factor for Preterm
Infants with Very Low Birth Weight. A Case-Control Study.
AB - Objective To evaluate whether the presence of maternal blood pressure reduces the
risks of morbidity, perinatal mortality and morbidity at 24 months of age in very
low birth weight infants (VLBWIs) compared with a control group. Methods A
retrospective, observational, case-control study. Total 49 VLBWIs were allocated
to the study group, called the maternal arterial hypertension group (AHG), and
matched with 44 in the control group (CG). The infants were assessed during
hospitalization and at 12 and 24 months corrected age at a specialized clinic.
For the assessment of growth, the World Health Organization (WHO) Anthro software
(Geneva, 2006) was used, and for the psychomotor assessment, the Denver II test
was used. Results In relation to the antenatal variables, the infants of the AHG
had more centralized circulation assessed by Doppler, received more
corticosteroids and magnesium sulfate, and were born by cesarean section more
frequently. In terms of the postnatal and in-hospital outcomes, the AHG had a
higher gestational age at birth (30.7 versus 29.6 weeks) and a lower frequency of
5-minute Apgar scores of less than 7 (26.5% versus 52.3%). The CG had a higher
rate of pulmonary dysplasia (30.2% versus 8.3%). There were no differences in
terms of hospital mortality, complications, somatic growth and functional
problems at 24 months of corrected age. Conclusion The presence of maternal
hypertension, especially preeclampsia, was not a protective factor against
morbidity, mortality and evolution in VLBWIs aged up to 24 months. Therefore, the
clinical practice should be focused on prolonging the pregnancy for as long as
possible in these conditions as well.
PMID- 28407657
TI - The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Indices of
Insulin Resistance and Hormonal Parameters in Patients with Polycystic Ovary
Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB - This study was conducted to determine the effects of omega-3 fatty acids and
vitamin E co-supplementation on indices of insulin resistance and hormonal
parameters in women with polycystic ovary syndrome (PCOS). This randomized double
blind, placebo-controlled trial was done on 68 women diagnosed with PCOS
according to the Rotterdam criteria aged 18-40 years old. Participants were
randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids
from flaxseed oil containing 400 mg alpha-Linolenic acid plus 400 IU vitamin E
supplements (n=34) or placebo (n=34) for 12 weeks. Hormonal parameters were
quantified at the beginning of the study and after 12-week intervention. After 12
weeks of intervention, compared to the placebo, omega-3 fatty acids and vitamin E
co-supplementation resulted in a significant decrease in insulin (-1.0+/-3.5 vs.
+2.7+/-6.6 uIU/mL, P=0.004), homeostasis model of assessment-estimated insulin
resistance (-0.2+/-0.8 vs. +0.6+/-1.5, P=0.005), homeostasis model of assessment
estimated B cell function (-4.3+/-14.3 vs. +10.5+/-24.5, P=0.004) and a
significant increase in quantitative insulin sensitivity check index (+0.006+/
0.02 vs. -0.01+/-0.04, P=0.008). Supplementation with omega-3 fatty acids plus
vitamin E led to significant reductions in serum total testosterone (-0.5+/-0.7
vs. -0.1+/-0.5 ng/mL, P=0.008) and free testosterone (-1.2+/-2.1 vs. -0.2+/-1.7,
P=0.04) compared to the placebo group. We did not observe any significant effect
of omega-3 fatty acids and vitamin E co-supplementation on fasting plasma glucose
and other hormonal profiles. Omega-3 fatty acids and vitamin E co-supplementation
for 12 weeks in PCOS women significantly improved indices of insulin resistance,
total and free testosterone.
PMID- 28407658
TI - Effect of Carnosine on Renal Function, Oxidation and Glycation Products in the
Kidneys of High-Fat Diet/Streptozotocin-Induced Diabetic Rats.
AB - High fat diet (HFD) and low dose of streptozotocin (STZ)-treated rats provide an
animal model for type 2 Diabetes Mellitus (T2DM). Oxidative stress plays a role
in the development of diabetic complications. Carnosine (CAR) has antioxidant and
antiglycating properties. We investigated effects of CAR on renal function,
oxidation and glycation products in HFD+STZ-rats. Rats were fed with HFD (60% of
total calories from fat) for 4 weeks and then a single dose STZ (40 mg/kg; i.p.)
was applied. Rats with blood glucose levels above 200 mg/dL were fed with HFD
until the end of the 12th week. CAR (250 mg/kg body weight; i.p.; 5 times a week)
was administered to rats for the last 4 weeks. Glycated hemoglobin (HbA1c),
glucose, lipids, and andrenal function tests in serum as well as reactive oxygen
species, malondialdehyde, protein carbonyl, advanced oxidation protein products,
advanced glycation end products (AGEs), antioxidant power, and antioxidant enzyme
activities and their mRNA expressions in kidneys were determined. CAR treatment
did not alter glucose and HbA1c, but it decreased serum lipids, creatinine, and
urea levels in HFD+STZ rats. Oxidation products of lipids and proteins and AGEs
levels decreased, but antioxidant enzyme activities and their mRNA expressions
remained unchanged due to CAR treatment. Our results indicate that CAR treatment
alleviated renal function and decreased accumulation of oxidation and glycation
products in kidneys in HFD+STZ-rats.
PMID- 28407659
TI - Peripheral Immunological Cells in Pregnant Women and their Change during
Diabetes.
AB - During the last decades the incidence of diabetes has dramatically increased as
well as the number of pregnant diabetic women. There is still missing data
regarding patterns and shifts of immune cell populations due to pregnancy with or
without diabetes. The study aimed to investigate the impact of pregnancy, type 1
diabetes (T1D) and gestational diabetes mellitus (GDM) on different immune cells
in female. The number and proportion of CD3-, CD4-, CD8- and gammadelta T-cells
as well as B-, NK-, NKT- and dendritic cells (DC) incl. rate of apoptosis was
analyzed in peripheral blood samples from 24 non-pregnant women, 24 pregnant
controls, 25 non-pregnant T1D, 18 women with GDM and 15 pregnant T1D (PT1D)
women. Compared to healthy controls, healthy pregnant women had reduced numbers
of lymphoid DC and gammadelta T-cells, while women with gestational diabetes
presented with increased numbers of gammadelta T-cells. Pregnant women with T1D
showed increased NKT cells and a decrease of NK cells compared to healthy
pregnant or non-pregnant T1D women. Apoptosis of gammadelta T-cells in healthy
pregnant women was found to be decreased in comparison to their non-pregnant
controls while apoptosis of myeloid and lymphoid DC was increased in pregnant T1D
in comparison to non-pregnant T1D. Those results may indicate that increased
complication rates during diabetic pregnancies might be due to an impaired
adaptation of the immune system.
PMID- 28407660
TI - The Effects of Calcium, Vitamins D and K co-Supplementation on Markers of Insulin
Metabolism and Lipid Profiles in Vitamin D-Deficient Women with Polycystic Ovary
Syndrome.
AB - Data on the effects of calcium, vitamins D and K co-supplementation on markers of
insulin metabolism and lipid profiles among vitamin D-deficient women with
polycystic ovary syndrome (PCOS) are scarce. This study was done to determine the
effects of calcium, vitamins D and K co-supplementation on markers of insulin
metabolism and lipid profiles in vitamin D-deficient women with PCOS. This
randomized double-blind, placebo-controlled trial was conducted among 55 vitamin
D-deficient women diagnosed with PCOS aged 18-40 years old. Subjects were
randomly assigned into 2 groups to intake either 500 mg calcium, 200 IU vitamin D
and 90 ug vitamin K supplements (n=28) or placebo (n=27) twice a day for 8 weeks.
After the 8-week intervention, compared with the placebo, joint calcium, vitamins
D and K supplementation resulted in significant decreases in serum insulin
concentrations (-1.9+/-3.5 vs. +1.8+/-6.6 uIU/mL, P=0.01), homeostasis model of
assessment-estimated insulin resistance (-0.4+/-0.7 vs. +0.4+/-1.4, P=0.01),
homeostasis model of assessment-estimated b cell function (-7.9+/-14.7 vs. +7.0+/
30.3, P=0.02) and a significant increase in quantitative insulin sensitivity
check index (+0.01+/-0.01 vs. -0.008+/-0.03, P=0.01). In addition, significant
decreases in serum triglycerides (-23.4+/-71.3 vs. +9.9+/-39.5 mg/dL, P=0.03) and
VLDL-cholesterol levels (-4.7+/-14.3 vs. +2.0+/-7.9 mg/dL, P=0.03) was observed
following supplementation with combined calcium, vitamins D and K compared with
the placebo. Overall, calcium, vitamins D and K co-supplementation for 8 weeks
among vitamin D-deficient women with PCOS had beneficial effects on markers of
insulin metabolism, serum triglycerides and VLDL-cholesterol levels.
PMID- 28407661
TI - Effect of Saxagliptin on Circulating Endothelial Progenitor Cells and Endothelial
Function in Newly Diagnosed Type 2 Diabetic Patients.
AB - Endothelial dysfunction is associated with the risk of cardiovascular
complications in diabetic patients. Endothelial progenitor cells (EPCs) and flow
mediated dilation (FMD) are common markers of endothelial function. In this
study, we aim to investigate whether the DPP-4 inhibitor saxagliptin modulate
EPCs number and FMD in newly diagnosed, treatment-naive type 2 diabetic patients.
This was a controlled, randomized, open-label clinical trial. Saxagliptin group
and metformin group consumed either saxagliptin 5 mg per day or metformin 1 500
mg per day respectively for 12 weeks. Changes of FMD and EPCs number after 12
week intervention were the primary endpoints. 31 patients were initially enrolled
and randomized to saxagliptin group (n=16) and metformin group (n=15). 27
patients completed the trial (saxagliptin group n=14 and metformin group n=13),
and 4 patients dropped out during the study. FMD and EPCs number increased
significantly in both saxagliptin group and metformin group, and there was no
significant difference between groups. 2-h postprandial plasma glucose, HbA1c and
diastolic blood pressure improved significantly in both groups, and there was no
significant difference between groups. Saxagliptin and metformin had comparable
beneficial effects on endothelial function.
PMID- 28407663
TI - The Diagnostic Value of Whole Blood lncRNA ENST00000550337.1 for Pre-Diabetes and
Type 2 Diabetes Mellitus.
AB - This study aims to investigate long noncoding RNA (lncRNA) as biomarker for pre
diabetes and T2DM. LncRNAs in the peripheral blood of 6 healthy individuals and 6
T2DM patients were collected for microarray analysis. Then 5 candidate biomarkers
from the differentially expressed lncRNAs were chosen and verified in a larger
independent cohort (control group=20; pre-diabetes group=20; and T2DM group=20).
The diagnostic capacity of ENST00000550337.1 was further tested in the third
cohort (control group, n=60; pre-diabetes group, n=63; and T2DM group, n=64). A
total of 17 lncRNAs were found to be differentially expressed between the 2
groups. 14 lncRNAs of these were upregulated in T2DM patients and 3 were
downregulated. 5 upregulated lncRNAs were selected as potential biomarkers and
verified in the second cohort, and the expression levels of 3 lncRNAs increased
gradually from the control group to the pre-diabetes group to the T2DM group. The
diagnostic value of ENST00000550337.1 was then tested in the third cohort, and
its high diagnostic value for pre-diabetes and T2DM was confirmed. LncRNA
ENST00000550337.1 is a potential diagnostic biomarker for pre-diabetes and T2DM.
PMID- 28407662
TI - Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus
and Metabolic Syndrome - A Randomized Controlled Explorative Study.
AB - There is increasing experimental evidence for beneficial effects of calorie
restriction and intermittent fasting in type 2 diabetes mellitus (T2DM). In
humans, prolonged fasting is established as a health-promoting complementary
treatment in Europe and claimed to improve metabolism by a complex hormetic
response. We aimed to investigate effects of a one-week fasting period compared
to usual care in T2DM by means of a pilot trial. Patients with manifest T2DM
medically treated with oral hypoglycemic agents and/or insulin were randomly
assigned to a 7-day fasting program followed by dietary advice or to usual care
and dietary advice only. Fasting was performed according to the method of
Buchinger with a nutritional energy intake of 300kcal/day by liquids only and
stepwise re-introduction of solid food thereafter. Outcomes were assessed
baseline and after 4 months. Of 46 enrolled participants, 32 (n=16 each group)
completed the trial and were included for final analyses. Fasting was well
accepted, there were no serious adverse events. After 4 months mean weight
decreased by 3.5 kg and 2.0 kg in the fasting vs. control group (p=0.03)
paralleled by greater reduction of abdominal circumference (p=0.001). Fasting led
to a significant decrease of systolic/diastolic blood pressure (p=0.01; p=0.003)
and increased quality-of-life (p=0.04), while for HbA1c, insulin and HOMA-index
only non-significant improvements were observed. Results of this study suggest
that prolonged fasting is feasible and might have beneficial clinical effects.
The effectiveness of fasting should be proved in larger confirmatory trials that
include intermittent fasting in follow-ups to enable more pronounced and long
term effects.
PMID- 28407664
TI - Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via
Leptin - A Threat To Diabetes Phytotherapy.
AB - Fenugreek (Trigonella foenum graecum), a medicinal herb with potent
antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This
study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT
(hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have
important role in normal and type-1 diabetic subjects. FSE (confirmed to contain
trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body
weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks.
Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum
levels of TRH, TSH (Thyroid stimulating hormone), fT3, fT4, insulin, leptin,
glucose; thyroperoxidase activity and growth of thyroid gland, food intake,
adiposity index were also studied FSE significantly down regulated prepro-TRH
mRNA expression; decreased serum TRH, TSH, fT3, fT4 levels, and regressed thyroid
gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed
control and diabetic rats. FSE decreased (p<0.005-0.001) adiposity index and
leptin secretion, increased food intake and body weight in all FSE-fed rats. FSE
improved insulin secretion, decreased glucose level but impaired HPT axis in
diabetic rats, indicating insulin-independent central hypothyroidism. Results
suggested that the dominant signal to hypothalamus suppressing HPT axis is the
fall in leptin level which i resulted from decreased adiposity index following
FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal
actions raises questions whether it can be safely used to treat diabetes and/or
hyperthyroidism as was suggested by many workers.
PMID- 28407665
TI - Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral
Adipose Tissue of 5alpha-Dihydrotestosterone-Induced Animal Model of Polycystic
Ovary Syndrome.
AB - Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder
associated with abdominal obesity, dyslipidemia and insulin resistance. Since
abdominal obesity is characterized by low-grade inflammation, the aim of the
study was to investigate whether visceral adipose tissue inflammation linked to
abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in
the animal model of polycystic ovary syndrome.Female Wistar rats were treated
with nonaromatizable 5alpha-dihydrotestosterone pellets in order to induce
reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose,
triglycerides, non-esterified fatty acids and insulin were determined in blood
plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor
kappa B intracellular distribution, macrophage migration inhibitory factor
protein level, as well as TNFalpha, IL6 and IL1beta mRNA levels. Insulin
sensitivity was assessed by intraperitoneal glucose tolerance test and
homeostasis model assessment index, and through analysis of insulin signaling
pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to
increased body weight, abdominal obesity and elevated triglycerides and non
esterified fatty acids, which were accompanied by the activation of nuclear
factor kappa B and increase in macrophage migration inhibitory factor, IL6 and
IL1beta levels in the visceral adipose tissue. In parallel, insulin sensitivity
was affected in 5alpha-dihydrotestosterone-treated animals only at the systemic
and not at the level of visceral adipose tissue.The results showed that abdominal
obesity and dyslipidemia in the animal model of polycystic ovary syndrome were
accompanied with low-grade inflammation in the visceral adipose tissue. However,
these metabolic disturbances did not result in decreased tissue insulin
sensitivity.
PMID- 28407666
TI - Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in
Patients with Haemodialysis.
AB - HbA1c is the most accepted laboratory parameter for the long term observation of
glucose control. There is still much of a debate about the use of HbA1c as a
metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and
erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte
turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In
102 CKD5 patients with and without diabetes mellitus, we examined the dose
dependent variability in HbA1c and fructosamine levels under haemodialysis and
treated with epoetin alpha (n=48) and a new generation agent with continuous
stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c
levels were affected by therapy with ESA treatments. ESA dose was inversely
correlated with HbA1c and an escalation of 10.000 IU per week induced an
estimated decrease of HbA1c of 0.6 percent. In addition, the increase of
reticulocyte number as a marker for erythropoiesis was significantly inversely
correlated with the increase of DeltaHbA1c. ESA treatments had no such effect on
the alternative metabolic parameter fructosamine. When compared, both therapeutic
agents had comparable success in attaining haemoglobin (Hb) target values.
C.E.R.A. showed better correlation and was more effective over a longer dose
interval. Our results show that HbA1c levels in patients should be carefully
interpreted based on interfering factors. Nevertheless, HbA1c is currently the
most consistent parameter for use ascertaining metabolic status of patients
suffering from diabetes mellitus.
PMID- 28407668
TI - Type 2 Diabetes is Associated with Lower Cardiorespiratory Fitness Independent of
Pulmonary Function in Severe Obesity.
AB - Both severe obesity and type 2 diabetes (T2DM) are associated with reduced
pulmonary function and reduced cardiorespiratory fitness. We investigated whether
T2DM further aggravates the impaired pulmonary function and cardiorespiratory
fitness in subjects with severe obesity. In this cross-sectional study pulmonary
function (forced expiratory volume within 1 s, FEV1; vital capacity, VC) was
assessed in 65 severely obese subjects with T2DM (T2DM group) and 65 severely
obese subjects without T2DM (non-T2DM group), pairwise matched for sex, age,
weight, and height. In 30 of the matched pairs, cardiorespiratory fitness was
assessed by an incremental bicycle test (peak workload, Wpeak, oxygen uptake,
VO2,peak). FEV1 and VC did not differ between the T2DM and non-T2DM group (all
p>=0.110), whereas Wpeak and VO2,peak - absolute values as well as relative to
body mass - were significantly lower in subjects with T2DM compared to those
without T2DM (all p<=0.030). Objective markers of maximal exertion, i. e.,
maximal heart rate and respiratory exchange ratio, did not differ between the 2
groups (both p>=0.245). The presence of T2DM in subjects with severe obesity is
associated with lower cardiorespiratory fitness but with no further reduction in
pulmonary function compared to subjects with severe obesity but without T2DM.
While the cause-effect relationship of this association is not yet clear, these
findings highlight the interplay between cardiorespiratory fitness and metabolic
health, even in subjects with severe obesity.
PMID- 28407667
TI - Monitoring Thyroid Function in Patients on Levothyroxine. Assessment of
Conformity to National Guidance and Variability in Practice.
AB - With demand for endocrine tests steadily increasing year-on-year, we examined
thyroid function test (TFT) frequencies in patients on levothyroxine replacement
therapy to assess the effect of initial TFT results and request source on TFT re
testing interval. All TFTs performed by the Clinical Biochemistry Departments at
the Salford Royal Hospital (2009-2012; 288 263 requests from 139 793 patients)
and University Hospital of North Midlands (2011-2014; 579 156 requests from 193
035 patients) were extracted from the laboratory computer systems. Of these, 54
894 tests were on 13 297 patients confirmed to be on levothyroxine therapy in the
test cohort (Salford) and 67 298 requests on 11 971 patients in the confirmatory
cohort (North Midlands). In the test cohort, median TFT re-testing interval in
the total group was 19.1 weeks (IQR 9.1-37.7 weeks), with clearly defined peaks
in TFT re-testing evident at 6 and 12 months and a prominent broad peak at 1-3
months. Median re-test interval was much lower than recommended (52 weeks) for
those with normal TFTs at 31.3 weeks (30.6 weeks for the confirmatory cohort).
Where thyroid-stimulating hormone (TSH) was elevated and free thyroxine (fT4) was
below the reference range, re-test interval was much longer than is recommended
(8 weeks) at 13.4-17.6 weeks (7.1-23.4 weeks in the confirmatory cohort), as was
the interval when TSH was below and fT4 was above the normal range, at 16.7-25.6
weeks (27.5-31.9 weeks in the confirmatory cohort). Our findings show that the
majority of TFT requests are requested outside recommended intervals and within
practice variability is high. A new approach to ensuring optimum monitoring
frequency is required. Direct requesting from the clinical laboratory may provide
one such solution.
PMID- 28407669
TI - Metformin Inhibits N-Methyl-N-Nitrosourea Induced Gastric Tumorigenesis in db/db
Mice.
AB - Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti
diabetic agent, has an inhibitory effect against gastric cancer cell in vitro.
However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis
in vivo is still not clear. In the present study, we aim to detect whether
metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and
which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were
divided into 3 groups (2 db/db mice groups and one wild type mice group). All
diabetic and non-diabetic mice were treated with N-Methyl-N-Nitrosourea (MNU) for
20 weeks to induce gastric tumorigenesis. At week 21, one db/db mice group were
treated with metformin (5 mg/ml) for 10 weeks and the other 2 groups were treated
with saline. Blood samples were collected for testing insulin and insulin-like
growth factor (IGF)-1. Stomach tissues were collected for histopathological
evaluation and mRNAs analysis. Metformin significantly decreased incidence of MNU
induced gastric dysplasia and cancer in diabetic db/db mice. Furthermore,
metformin reduced serum insulin as well as IGF-1, and also suppressed expression
of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines
mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF
2 receptor expressions. The results show that metformin can prevent the risk of
gastric cancer in type 2 diabetes and the protective mechanisms may involve in an
inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer
related pro-inflammatory cytokines.
PMID- 28407671
TI - ?
PMID- 28407670
TI - Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes -
What We Know so Far and the Missing Links.
AB - Hyperglycemia explains the development of late diabetic complications in patients
with diabetes type 1 and type 2 only partially. Most therapeutic efforts relying
on intensive glucose control failed to decrease the absolute risk for
complications by more than 10%, especially in patients with diabetes type 2.
Therefore, alternative pathophysiological pathways have to be examined, in order
to develop more individualized treatment options for patients with diabetes in
the future. One such pathway might be the metabolism of dicarbonyls, among them
methylglyoxal and the accumulation of advanced glycation end products. Here we
review currently available epidemiological data on dicarbonyls and AGEs in
association with human diabetes type 1 and type 2.
PMID- 28407672
TI - [Test Your Knowledge].
PMID- 28407673
TI - [Tracheostomy Home Care of Patients after Long Term Ventilation on the ICU - a
Position Paper].
PMID- 28407674
TI - [Strategies for the Treatment of Community-Acquired Pneumonia in HIV-Positive
Patients].
AB - Study purpose According to the Robert Koch Institute, 84,700 people in Germany
suffer from HIV infection. One-third of the affected persons is over 50 years
old. In Germany, community-acquired pneumonia (CAP) is a widespread disease with
more than 250,000 cases per year. Incidence and mortality increase with the age
of the affected individuals. For this reason, diagnostic and therapeutic
strategies are needed to guide medical care of HIV-infected patients presenting
with CAP. Methodology HIV therapists were interviewed about their diagnostic
approach, risk stratification strategy and therapeutic approach to HIV-associated
community-acquired pneumonia (HIV +/CAP) using a questionnaire. 56 completed
questionnaires were analysed. Results Half of the respondents reported that CAP
occurred in 1 to 5 % of HIV-infected individuals per year. This indicates an
estimated number of up to 4200 HIV +/CAP cases per year in Germany - a much
higher number than expected from the literature. 58.9 % of respondents considered
that the pathogenic spectrum did not differ in HIV +/CAP from non-HIV/CAP. 80.3 %
of respondents applied the same antibiotic regimens in HIV +/CAP as used in
patients with non-HIV/CAP. Conclusion Even though over 40 % of HIV therapists
agree that the pathogenic spectrum of HIV +/CAP differs from that of non-HIV/CAP,
over 80 % of therapists managed these patients in accordance with the S3
guidelines for non-immunocompromised CAP-patients, because specific guidelines
for the treatment of HIV +/CAP are lacking. Since specific data on the aetiology
and the clinical course of HIV +/CAP depending, for instance, on CD4-count and
antiretroviral therapy are missing, we feel that the clinical course of HIV +/CAP
should be further analysed in the context of prospective cohort studies.
PMID- 28407675
TI - [Extracorporeal CO2 Elimination (ECCO2R) for Hypercapnic Respiratory Failure:
From Pathophysiology to Clinical Application].
AB - Extracorporeal CO2 removal (ECCO2R) is becoming an increasingly established
treatment option for patients with acute severe hypercapnic respiratory failure.
Technically, pumpless arterio-venous systems using the natural arterio-venous
pressure gradient and also pump-driven veno-venous systems are available. Here,
veno-venous ECCO2R has become the preferred technique, as settings for arterio
venous ECCO2R are restricted and side effects are more common with arterio-venous
ECCO2R. Using veno-venous ECCO2R with blood flow rates up to 450 ml/min 60 to 80
ml CO2 can be removed per minute corresponding to 20 to 30 % of the total amount
of CO2 production. However, in case of very severe hypercapnic respiratory
failure with severe respiratory acidosis (pH 7.1 or less) blood flow rates of
around 1000 ml/min are required for compensating severe respiratory acidosis
corresponding to the elimination of 50 to 60 % of the total amount of CO2
production. Relevant side effects include the activation of blood coagulation and
associated bleeding complications. Two recent case-control studies in severely
exacerbated COPD patients could demonstrate that intubation rates can be reduced
by the application of ECCO2R, but this was associated with non-ignorable side
effects. Therefore, randomized controlled trials are urgently needed to more
precisely establish the risks and benefits of ECCO2R when aimed at avoiding
intubation.
PMID- 28407676
TI - ?
PMID- 28407678
TI - Transplacental Passage of Acetaminophen in Term Pregnancy (Podcast).
PMID- 28407680
TI - Transplantation of mesenchymal stem cells reverses behavioural deficits and
impaired neurogenesis caused by prenatal exposure to valproic acid.
AB - Neurodevelopmental impairment can affect lifelong brain functions such as
cognitive and social behaviour, and may contribute to aging-related changes of
these functions. In the present study, we hypothesized that bone marrow-derived
mesenchymal stem cells (MSC) administration may repair neurodevelopmental
behavioural deficits by modulating adult hippocampal neurogenesis. Indeed,
postnatal intracerebral transplantation of MSC has restored cognitive and social
behaviour in mice prenatally exposed to valproic acid (VPA). MSC transplantation
also restored post-developmental hippocampal neurogenesis, which was impaired in
VPA-exposed mice displaying delayed differentiation and maturation of newly
formed neurons in the granular cell layer of the dentate gyrus. Importantly, a
statistically significant correlation was found between neuronal differentiation
scores and behavioural scores, suggesting a mechanistic relation between the two.
We thus conclude that post-developmental MSC administration can overcome prenatal
neurodevelopmental deficits and restore cognitive and social behaviours via
modulation of hippocampal adult neurogenesis.
PMID- 28407679
TI - Activated-PAK4 predicts worse prognosis in breast cancer and promotes
tumorigenesis through activation of PI3K/AKT signaling.
AB - The p21-activated kinase 4 (PAK4) is sufficient to transform noncancerous mammary
epithelial cells and to form tumors in the mammary glands of mice. The
accumulated information suggests that PAK4 might be an oncogenic protein in
breast cancer. In this study, we sought to identify the role for PAK4 in breast
cancer progression. Immunohistochemical study revealed that high PAK4 expression
is associated with larger tumor size, lymph node metastasis, and advanced stage
cancer in 93 invasive breast carcinoma patients. Moreover, high PAK4 expression
was significantly associated with poor overall and disease-free survival. PAK4
remained an independent adverse prognosticator after univariate and multivariate
analysis. Ectopic expression of wild-type PAK4 in MDA-MB-231 cells activated
PI3K/AKT signaling and resulted in the enhancement of the cell proliferation,
migration, and invasion, whereas PAK4-induced effects were blocked by the PAK4
kinase inhibitor PF- 3758309, PAK4 siRNAs or the PI3K inhibitor LY294002.
Furthermore, a kinase-active PAK4 (S474E) strongly induced PI3K/AKT activation,
and promoted proliferation, migration and invasion in breast cancer cells. A
kinase-inactive PAK4 KD (K350A/K351A) did partially upregulate PI3K/AKT, and
promoted invasive phenotype. Taken together, these findings suggest that PAK4
activated PI3K/AKT signaling is both kinase-dependent and -independent, which
contributes to breast cancer progression. Thus, our results imply that dual
inhibition of PAK4 and PI3K/AKT signaling might be a potential therapeutic
approach for breast cancer therapy.
PMID- 28407681
TI - Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to
mesenchymal transition.
AB - Runx1 is a well characterized transcription factor essential for hematopoietic
differentiation and Runx1 mutations are the cause of leukemias. Runx1 is highly
expressed in normal epithelium of most glands and recently has been associated
with solid tumors. Notably, the function of Runx1 in the mammary gland and how it
is involved in initiation and progression of breast cancer is still unclear. Here
we demonstrate the consequences of Runx1 loss in normal mammary epithelial and
breast cancer cells. We first observed that Runx1 is decreased in tumorigenic and
metastatic breast cancer cells. We also observed loss of Runx1 expression upon
induction of epithelial-mesenchymal transition (EMT) in MCF10A (normal-like)
cells. Furthermore depletion of Runx1 in MCF10A cells resulted in striking
changes in cell shape, leading to mesenchymal cell morphology. The epithelial
phenotype could be restored in breast cancer cells by re-expressing Runx1.
Analyses of breast tumors and patient data revealed that low Runx1 expression is
associated with poor prognosis and decreased survival. We addressed mechanisms
for the function of Runx1 in maintaining the epithelial phenotype and find Runx1
directly regulates E-cadherin; and serves as a downstream transcription factor
mediating TGFbeta signaling. We also observed through global gene expression
profiling of growth factor depleted cells that induction of EMT and loss of Runx1
is associated with activation of TGFbeta and WNT pathways. Thus these findings
have identified a novel function for Runx1 in sustaining normal epithelial
morphology and preventing EMT and suggest Runx1 levels could be a prognostic
indicator of tumor progression.
PMID- 28407682
TI - Genetic characterization and antiretroviral resistance mutations among treatment
naive HIV-infected individuals in Jiaxing, China.
AB - The aim of this study was to characterize HIV-1 genotypes and antiretroviral
resistance mutations among treatment-naive HIV-infected individuals in Jiaxing,
China. The HIV-1 partial polymerase (pol) genes in 93 of the 99 plasma samples
were successfully amplified and analyzed. Phylogenetic analysis revealed the
existence of five HIV-1 genotypes, of which the most prevalent genotype was
CRF01_AE (38.7%), followed by CRF07_BC (34.4%), CRF08_BC (16.1%), subtype B/B'
(5.4%), and CRF55_01B (2.1%). Besides, three types of unique recombination forms
(URFs) were also observed, including C/F2/A1, CRF01_AE/B, and CRF08_BC/CRF07_BC.
Among 93 amplicons, 46.2% had drug resistance-associated mutations, including
23.7% for protease inhibitors (PIs) mutations, 1.1% for nucleoside reverse
transcriptase inhibitors (NRTIs) mutations, and 20.4% for non-nucleoside reverse
transcriptase inhibitors (NNRTIs) mutations. Six (6.5%) out of 93 treatment-naive
subjects were identified to be resistant to one or more NNRTIs, while resistance
to NRTIs or PIs was not observed. Our study showed the genetic diversity of HIV-1
strains circulating in Jiaxing and a relative high proportion of antiretroviral
resistance mutations among treatment-naive patients, indicating a serious
challenge for HIV prevention and treatment program.
PMID- 28407683
TI - The effects of high glucose on tendon-derived stem cells: implications of the
pathogenesis of diabetic tendon disorders.
AB - Patients with diabetes are at great risk to suffer many musculoskeletal
disorders, such as tendinopathy, tendon rupture and impaired tendon healing.
However, the pathogenesis of these tendon disorders still remains unclear. In
this study, we aimed to investigate the effects of high glucose on cell
proliferation, cell apoptosis and tendon-related markers expression of tendon
derived stem cells (TDSCs) in vitro. These findings might provide new insights
into the pathogenesis of diabetic tendon disorders. The cell proliferative
ability and apoptosis rate of TDSCs in different groups were evaluated by MTT
assay and Annexin V-FITC/PI staining assay. The mRNA expression of tendon-related
markers (Scleraxis and Collagen I alpha 1 chain) were assessed by qRT-PCR. The
protein expression of tendon-related markers (Tenomodulin and Collagen I) were
measured by Western blotting. The proliferative ability of TDSCs treated with
high glucose (15mM and 25mM) decreased significantly at day1, day3 and day5. The
cell apoptosis of TDSCs increased significantly when they were cultured with high
glucose for 48h in vitro. The gene expression of Scleraxis and Collagen I alpha 1
chain in TDSCs decreased significantly when they were treated with high glucose
for 24h and 48h. The protein expression of Tenomodulin and Collagen I in TDSCs
decreased significantly when they were treated with high glucose for 24h and 48h.
High glucose could inhibit cell proliferation, induce cell apoptosis and suppress
the tendon-related markers expression of TDSCs in vitro. These findings might
account for some pathological mechanisms underlying the pathogenesis of diabetic
tendon disorders.
PMID- 28407684
TI - Atorvastatin inhibits the immediate-early response gene EGR1 and improves the
functional profile of CD4+T-lymphocytes in acute coronary syndromes.
AB - Background- Adaptive immune-response is associated with a worse outcome in acute
coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid
levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment
in acute coronary syndromes on CD4+T-cells, and the underlying molecular
mechanisms.Approach and results- Blood samples were collected from 50 statin
naive acute coronary syndrome patients. We assessed CD4+T-cell activation by flow
cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell
related genes by RT-qPCR, and protein expression by Western-blot, before and
after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 MUg/ml
(corresponding to blood levels achieved with doses of 10-40-80 mg, respectively).
After incubation, we found a significant decrease in interferon-gamma-producing
CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10
producing CD4+CD25highT-cells (P < 0.001). Atorvastatin increased the expression
of 2 genes and decreased the expression of 12 genes (in particular, EGR1,
FOS,CCR2 and toll like receptor-4; >3-fold changes).The in-vivo effects of
atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at
baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene
expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels
decreased at 48h (P = 0.03).Conclusions-In acute coronary syndromes, the effects
of atorvastatin on immune system might be partially related to the inhibition of
the master regulator gene EGR1. Our finding might offer a causal explanation on
why statins improve the early outcome in acute coronary syndromes.
PMID- 28407685
TI - Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose
microenvironment, with released fatty acids enhancing the invasiveness of
pancreatic cancer cells.
AB - Pancreatic cancer progression involves components of the tumor microenvironment,
including stellate cells, immune cells, endothelial cells, and the extracellular
matrix. Although peripancreatic fat is the main stromal component involved in
extra-pancreatic invasion, its roles in local invasion and metastasis of
pancreatic cancer remain unclear. This study investigated the role of adipose
tissue in pancreatic cancer progression using genetically engineered mice (Pdx1
Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat
invasion. Mice fed a high fat diet had significantly larger primary pancreatic
tumors and a significantly higher rate of distant organ metastasis than mice fed
a standard diet. In the organotypic fat invasion model, pancreatic cancer cell
clusters were smaller and more elongated in shape and showed increased fibrosis.
Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell
invasiveness and gemcitabine resistance, as well as inducing morphologic changes
in cancer cells and increasing the numbers of lipid droplets in their cytoplasm.
The concentrations of oleic, palmitoleic, and linoleic acids were higher in
adipose tissue-derived conditioned medium than in normal medium, with these fatty
acids significantly enhancing the migration of cancer cells. Mature adipocytes
were smaller and the concentration of fatty acids in the medium higher when these
cells were co-cultured with cancer cells. These findings indicate that lipolytic
and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness
and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid
uptake by cancer cells may be a novel therapy targeting interactions between
cancer and stromal cells.
PMID- 28407686
TI - Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary
hospital in China: A real-world study.
AB - The current clinical reality of tumor stages and primary treatments of
hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the
distribution of tumor stages and primary treatment modalities among a large
population of patients with primary HCC. Medical records of patients treated
between January 2003 and October 2013 for primary HCC at our tertiary hospital in
China were retrospectively reviewed. A total of 6241 patients were analyzed. The
distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage
0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of
Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa,
1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%;
stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was
hepatic resection for patients with BCLC-0/A/B disease, and transarterial
chemoembolization for patients with BCLC-C disease. Both these treatments were
the most frequent for patients with HKLC I to IIIb disease, while systemic
chemotherapy was the most frequent first-line therapy for patients with HKLC IVa
or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease
was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C
disease, and of HKLC I to IIIb disease, were relatively high in our patient
population. Hepatic resection and transarterial chemoembolization were frequent
first-line therapies.
PMID- 28407687
TI - Cytokeratin 19 promoter directs the expression of Cre recombinase in various
epithelia of transgenic mice.
AB - Cytokeratin 19 (K19) is expressed in various differentiated cells, including
gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here,
we generated a transgenic mouse line, K19-Cre, in which the expression of Cre
recombinase was controlled by the promoter of K19. To test the tissue
distribution and excision activity of Cre recombinase, K19-Cre transgenic mice
were bred with Rosa26 reporter strain and a mouse strain that carries PTEN
conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in
the stomach, lung and intestine, while in stomach, lung, and liver at protein
level. The immunoreactivity to Cre was strongly observed the cytoplasm of
gastric, bronchial and intestinal epithelial cells. Cre activity was detectable
in gastric, bronchial and intestinal epithelial cells, according to LacZ
staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach,
intestine, lung, liver and breast, the former two of which were verified by in
situ PCR. There appeared breast cancer with PTEN loss. These data suggest that
K19 promoter may be a useful tool to study the pathophysiological functions of
cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell
specificity of neoplasia is not completely attributable to the cell-specific
expression of oncogenes and cell-specific loss of tumor suppressor genes.
PMID- 28407688
TI - NPC-26 kills human colorectal cancer cells via activating AMPK signaling.
AB - NPC-26 is novel mitochondrion-interfering compound. The current study tested its
potential effect against colorectal cancer (CRC) cells. We demonstrated that NPC
26 induced potent anti-proliferative and cytotoxic activities against CRC cell
lines (HCT-116, DLD-1 and HT-29). Activation of AMP-activated protein kinase
(AMPK) signaling mediated NPC-26-induced CRC cell death. AMPKalpha1 shRNA
knockdown or dominant negative mutation abolished NPC-26-induced AMPK activation
and subsequent CRC cell death. NPC-26 disrupted mitochondrial function, causing
mitochondrial permeability transition pore (mPTP) opening and reactive oxygen
species (ROS) production. ROS scavengers (NAC or MnTBAP) and mPTP blockers
(cyclosporin A or sanglifehrin A) blocked NPC-26-induced AMPK activation and
attenuated CRC cell death. Significantly, intraperitoneal injection of NPC-26
potently inhibited HCT-116 tumor growth in severe combined immuno-deficient
(SCID) mice. Yet, its anti-tumor activity was significantly weakened against
AMPKalpha1-silenced HCT-116 tumors. Together, we conclude that NPC-26 kills CRC
cells possibly via activating AMPK signaling.
PMID- 28407689
TI - Radioiodinated indomethacin amide for molecular imaging of cyclooxygenase-2
expressing tumors.
AB - Cyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available
imaging probes display relatively low tumor to background ratios (smaller than
2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo
molecular imaging of COX-2 expressing carcinoma. Radioiodinated Ind derivatives
Ind-NH-(CH2)4-NH-3-[I-125]I-Bz ([I-125]5), Ind-NH-(CH2)4-NH-5-[I-124/125]I-Nic
([I-124/125]6) and Ind-NH-(CH2)4-NH-5-[I-125]I-Iphth ([I-125]7) were prepared
from the respective SnBu3-precursors (45-80% radiochemical yield; > 95%
radiochemical purity). The cellular uptake of [I-125]5 and [I-125]6 correlated
with COX-2 expression determined by SDS page/Western blot analysis. [I-125]5 was
predominantly localized in the cell membrane while [I-125]6 was internalized and
displayed a diffuse and favorable cytoplasmic distribution. In contrast, [I-125]7
showed only low uptake in COX-2 positive cells. Co-incubation with the COX-2
inhibitor Celecoxib led to an almost complete suppression of cellular uptake of
[I-125]5 and [I-125]6. In vivo molecular imaging using positron emission
tomography (PET) in SCID mice xenografted with COX-2+ (HT29) and COX-2- (HCT116)
human colorectal carcinoma cells was performed for [I-124]6. HT29 xenografts
displayed a significantly higher uptake than HCT-116 xenografts (5.6 +/- 1.5 vs.
0.5 +/- 0.1 kBq/g, P < 0.05) with an extraordinary high tumor to muscle ratio
(50.3 +/- 1.5). Immunohistological staining correlated with the imaging data. In
conclusion, the novel radioiodinated indomethacin derivative ([I-124/125]6) could
become a valuable tool for development of molecular imaging probes for
visualization of COX-2 expressing tumors.
PMID- 28407690
TI - The suppressing effects of BTG3 expression on aggressive behaviors and phenotypes
of colorectal cancer: An in vitro and vivo study.
AB - Here, we found that down-regulated expression of BTG3 might be positively
correlated with colorectal carcinogenesis and its overexpression suppressed
proliferation, glycolysis, mitochondrial respiration, cell cycle progression,
migration, and invasion, and induced apoptosis, senescence and differentiation in
SW480 and SW620 cells. After treated with cisplatin, MG132, paclitaxel and SAHA,
BTG3 transfectants exhibited lower viability and higher apoptosis than the
control in both time- and dose-dependent manners. BTG3 overexpression up-
regulated the protein expression of Cyclin E, p16, p27, NF-kappaB, p38alpha/beta,
XIAP, Bcl-2, ATG14 and p53, but down-regulated the mRNA expression of MRP1, BCRP,
and mTOR in SW480 and SW620 cells. BTG3 overexpression inhibited tumor growth of
SW620 cells by suppressing proliferation and inducing apoptosis. It was suggested
that down-regulated BTG3 expression might be considered as a marker for
colorectal carcinogenesis. BTG3 overexpression might reverse the aggressive
phenotypes and be employed as a potential target for gene therapy of colorectal
cancer.
PMID- 28407692
TI - MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of
breast cancer cells.
AB - Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth
factor beta 1 (TGFbeta1)-mediated fibrosis through suppressing epithelial
mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the
effects of TGFbeta1 in breast cancer (BC) tumorigenesis-related EMT.
Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we
detected significantly lower levels of BMP7 and significantly higher levels of
microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor
breast tissue. BMP7 and miR-137 levels were correlated inversely. Additionally,
the high miR-137 levels in BC specimens were correlated with reduced patient
survival. In vitro, overexpression of miR-137 significantly increased cell EMT
and invasion, while depletion of miR-137 significantly decreased cell EMT and
invasion in BC cells. The increases in BC cell invasiveness by miR-137 appeared
to result from its suppression of BMP7, through direct binding of miR-137 to the
3'-UTR of BMP7 mRNA, thereby blocking its protein translation in BC cells. This
study sheds light on miR-137 as a crucial factor that enhances BC cell EMT and
invasiveness, and points to miR-137 as a promising innovative therapeutic target
for BC treatment.
PMID- 28407691
TI - TET2 and MEG3 promoter methylation is associated with acute myeloid leukemia in a
Hainan population.
AB - The promoter of MEG3, which encodes the long non-coding RNA (lncRNA) MEG3, is
often hypermethylated in acute myeloid leukemia (AML). Additionally, the Tet
methylcytosine dioxygenase 2 gene (TET2) is frequently inactivated, which can
lead to impaired DNA methylation and promote AML development. We examined the
association between TET2 and MEG3 promoter hypermethylation in Hainan patients
with AML. The expression of MEG3, TET2, miR-22-3p, and miR-22-5p was assessed in
bone marrow samples from AML patients and healthy controls using real-time
quantitative PCR. Using Sequenom MassARRAY technology, we compared MEG3 promoter
methylation in AML patients and healthy controls. MEG3 expression was lower in
AML patients than in the controls (P = 0.136). Moreover, there was greater
methylation of MEG3 promoter in the AML patients than the controls (P < 0.05).
Methylation of the MEG3 promoter correlated negatively with TET2 expression (P <
0.05, r < 0). Likewise there was a negative correlation between TET2 activity and
MEG3 promoter methylation (P < 0.05, r < 0). These results suggest that
hypermethylation of the MEG3 promoter in AML may result from decreased TET2
activity. These data provide insight into the molecular mechanisms underlying AML
development and progression.
PMID- 28407695
TI - Oleuropein, unexpected benefits!
PMID- 28407694
TI - Molecular mechanisms of activating c-MET in KSHV+ primary effusion lymphoma.
AB - The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal
causative agent of primary effusion lymphoma (PEL), which is mostly seen in
immunosuppressed patients. PEL is a rapidly progressing malignancy with a median
survival time of approximately 6 months even under the conventional chemotherapy.
We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is
highly activated in PEL cells and represents a promising therapeutic target
(Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET
activation within PEL cells remain largely unknown. To solve this puzzle, here we
have utilized the next generation sequencing (NGS) based bioinformatics approach
to investigate the genomic landscape of the c-MET gene and we found that there's
no single nucleotide variations (SNVs) occurred in the c-MET genomic regions in a
cohort of PEL samples. Consistently, Sanger sequencing analysis of frequently
mutated exons such as exon 10, 14 and 19 shows no mutation of these c-MET exons
in PEL cell-lines, which further supports the notion that mutations are not the
major mechanism responsible for c-MET activation in PEL. Further, we found that a
transmembrane receptor protein, Plexin-B1, is expressed in PEL cell-lines, which
is required for c-MET-mediated PEL cell survival via direct protein interaction.
PMID- 28407693
TI - Discovery and characterization of a novel irreversible EGFR mutants selective and
potent kinase inhibitor CHMFL-EGFR-26 with a distinct binding mode.
AB - EGFR T790M mutation accounts for about 40-55% drug resistance for the first
generation EGFR kinase inhibitors in the NSCLC. Starting from ibrutinib, a highly
potent irreversible BTK kinase inhibitor, which was also found to be moderately
active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR
inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants
including L858R, del19, and L858R/T790M. It displayed proper selectivity window
between the EGFR mutants and the wide-type. CHMFL-EGFR-26 exhibited good
selectivity profile among 468 kinases/mutants tested (S score (1)=0.02). In
addition, X-ray crystallography revealed a distinct "DFG-in" and "cHelix-out"
inactive binding mode between CHMFL-EGFR-26 and EGFR T790M protein. The compound
showed highly potent anti-proliferative efficacy against EGFR mutant but not wide
type NSCLC cell lines through effective inhibition of the EGFR mediated signaling
pathway, induction of apoptosis and arresting of cell cycle progression. CHMFL
EGFR-26 bore acceptable pharmacokinetic properties and demonstrated dose
dependent tumor growth suppression in the H1975 (EGFR L858R/T790M) and PC-9 (EGFR
del19) inoculated xenograft mouse models. Currently CHMFL-EGFR-26 is undergoing
extensive pre-clinical evaluation for the clinical trial purpose.
PMID- 28407696
TI - RUNX1, a new regulator of EMT in breast cancer.
PMID- 28407697
TI - Cytosolic Hsp90alpha and its mitochondrial isoform Trap1 are differentially
required in a breast cancer model.
AB - The Hsp90 family of molecular chaperones includes the cytosolic isoforms
Hsp90alpha and Hsp90beta, and the mitochondrial isoform Trap1. Hsp90alpha/beta
support a large number of client proteins in the cytoplasm and the nucleus
whereas Trap1 regulates oxidative phosphorylation in mitochondria. Many of the
associated proteins and cellular processes are relevant to cancer, and there is
ample pharmacological and genetic evidence to support the idea that
Hsp90alpha/beta and Trap1 are required for tumorigenesis. However, a direct and
comparative genetic test in a mouse cancer model has not been done. Here we
report the effects of deleting the Hsp90alpha or Trap1 genes in a mouse model of
breast cancer. Neither Hsp90alpha nor Trap1 are absolutely required for mammary
tumor initiation, growth and metastasis induced by the polyoma middle T-antigen
as oncogene. However, they do modulate growth and lung metastasis in vivo and
cell proliferation, migration and invasion of isolated primary carcinoma cells in
vitro. Without Hsp90alpha, tumor burden and metastasis are reduced, correlating
with impaired proliferation, migration and invasion of cells in culture. Without
Trap1, the appearance of tumors is initially delayed, and isolated cells are
affected similarly to those without Hsp90alpha. Analysis of expression data of
human breast cancers supports the conclusion that this is a valid mouse model
highlighting the importance of these molecular chaperones.
PMID- 28407699
TI - Reinnervated muscle fiber type-grouping-inevitable?
PMID- 28407700
TI - Correction: DAPK loss in colon cancer tumor buds: implications for migration
capacity of disseminating tumor cells.
PMID- 28407698
TI - Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal
induced aging rats through enhanced autophagy and reduced apoptosis via AMPK
FOXO3a signal pathway.
AB - The quality control of skeletal muscle is a continuous requirement throughout the
lifetime, although its functions and quality present as a declining trend during
aging process. Dysfunctional or deficient autophagy and excessive apoptosis may
contribute to the atrophy of senescent skeletal muscle. Spermidine, as a natural
polyamine, can be involved in important cellular functions for lifespan extension
and stress resistance in several model organisms through activating autophagy.
Similarly, cellular autophagic responses to exercise have also been extensively
investigated. In the present study, in order to confirm the mitigation or
amelioration of skeletal muscle atrophy in aging rats through spermidine coupled
with exercise intervention and explore corresponding mechanisms, the rat model
with aging-related atrophy of skeletal muscle was established by intraperitoneal
injection of D-galactose (D-gal) (200 mg/kg?d), and model rats were subjected to
the intervention with spermidine (5 mg/kg?d)) or swimming (60 min/d, 5 d/wk) or
combination for 42 days. Spermidine coupled with exercise could attenuate D-gal
induced aging-related atrophy of skeletal muscle through induced autophagy and
reduced apoptosis with characteristics of more autophagosomes, activated
mitophagy, enhanced mitochondrial quality, alleviated cell shrinkage, and less
swollen mitochondria under transmission scanning microscopic observation.
Meanwhile, spermidine coupled with exercise could induce autophagy through
activating AMPK-FOXO3a signal pathway with characterization of increased Beclin1
and LC3-II/LC3-I ratio, up-regulated anti-apoptotic Bcl-2, down-regulated pro
apoptotic Bax and caspase-3, as well as activated AMPK and FOXO3a. Therefore,
spermidine combined with exercise can execute the prevention or treatment of D
gal-induced aging-related skeletal muscle atrophy through enhanced autophagy and
reduced apoptosis mediated by AMPK-FOXO3a signal pathway.
PMID- 28407701
TI - Correction: A new immunohistochemistry prognostic score (IPS) for recurrence and
survival in resected pancreatic neuroendocrine tumors (PanNET).
PMID- 28407702
TI - Assessment of Clinical Symptoms in Lumbar Foraminal Stenosis Using the Japanese
Orthopaedic Association Back Pain Evaluation Questionnaire.
AB - OBJECTIVE: It is important to develop an easy means of diagnosing lumbar
foraminal stenosis (LFS) in a general practice setting. We investigated the use
of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire
(JOABPEQ) to diagnose LFS in symptomatic patients. METHODS: Subjects included 13
cases (mean age, 72 years) with LFS, and 30 cases (mean age, 73 years) with
lumbar spinal canal stenosis (LSCS) involving one intervertebral disc. The visual
analogue scale score for low back pain and leg pain, the JOABPEQ were evaluated.
RESULTS: Those with LFS had a significantly lower JOA score (p<0.001), while
JOABPEQ scores (p<0.05) for lumbar dysfunction and social functioning impairment
(p<0.01) were both significantly lower than the scores in LSCS. The following
JOABPEQ questionnaire items (LFS vs. LSCS, p-value) for difficulties in: sleeping
(53.8% vs. 16.6%, p<0.05), getting up from a chair (53.8% vs. 6.6%, p<0.001),
turning over (76.9% vs. 40%, p<0.05), and putting on socks (76.9% vs. 26.6%,
p<0.01) such as pain during rest, and signs of intermittent claudication more
than 15 minutes (61.5% vs. 26.6%, p<0.05) were all significantly more common with
LFS than LSCS. CONCLUSION: Results suggest that of the items in the JOABPEQ, if
pain during rest or intermittent claudication is noted, LFS should be kept in
mind as a cause during subsequent diagnosis and treatment. LFS may be easily
diagnosed from LSCS using this established patient-based assessment method.
PMID- 28407703
TI - Determination of the Effect of Diameter of the Sac on Prognosis in 64 Cases
Operated for Meningomyelocele.
AB - OBJECTIVE: To examine the effect of meningomyelocele sac size on prognosis by
retrospective review of 64 cases operated for meningomyelocele between January
2009 and December 2012. METHODS: We evaluated newborn babies operated for
meningomyelocele by retrospectively reviewing their files for head circumference,
location and with of the defect, accompanying anomalies, treatments administered,
drugs that mother used during pregnancy. Based on the defect size, 3 patient
groups were created as 0-24 cm2 (group I), 25-39 cm2 (group II), and 40 cm2 and
above (group III). RESULTS: Throughout the study, 64 babies were evaluated. Mean
head circumference was 37.4 cm (range, 30.7-50 cm). Based on their location, 49
of the defects (76.5%) were lumbar, 7 (10.9%) were thoracolumbar, 4 (6.2%) were
thoracic, 3 (3.1%) were sacral, 1 (1.5%) was cervical. Mean size of the
meningomyelocele sac was 4.7 cm*5.8 cm (range, 1 cm*1 cm-10 cm*8 cm), 13 of the
babies (20.3%) had skin defect requiring flap. According to accompanying
anomalies, 47 of the babies (73.4%) had hydrocephalus, 7 (10.9%) had club foot, 1
(1.5%) had diastematomyelia, 1 (1.5%) had tethered cord. Thirty-nine of the
babies (60.9%) had paraplegia, 10 (15.6%) had paraparesis, 8 (12.5%) had
monoplegia; neurological examination in the remaining 7 babies was normal.
CONCLUSION: In our study, increased diameter of meningomyelocele sac was
associated with greater amount of neural tissue within the sac, which worsens the
prognosis. Sac localization was not changing prognosis but infection rates,
hospitalization duration were increased in babies with bigger diameter of sacs.
PMID- 28407704
TI - Delayed Epidural Mucin Collection after Surgery for Spinal Metastatic Pancreatic
Adenocarcinoma.
AB - A rare case of delayed large epidural mucin collection causing neurologic deficit
after surgery for metastatic pancreatic cancer is reported. A 65-year-old man
presented with intractable upper-thoracic back pain radiating to the chest and
gait disturbance. He had a history of subtotal pancreatectomy due to intraductal
papillary mucinous neoplasm (IPMN) of the pancreas and concurrent chemotherapy.
Eight months after pancreatectomy, multiple thoracic spinal metastasis was
diagnosed with routine up positron emission tomography-computed tomography.
Radiotherapy for spinal metastasis and subsequent chemotherapy was carried out.
Sixteen months after pancreatectomy, gait disturbance occurred and follow-up
thoracic magnetic resonance imaging (MRI) showed aggravation of metastasis at T2
and T4 compressing the spinal cord. We performed a decompressive laminectomy with
subtotal resection of the tumor masses and pedicle screw fixation at C7-T6.
Neurologic status improved after the operation. Histopathologic examinations
revealed the tumor as metastatic mucin producing adenocarcinoma. Three months
after surgery, motor weakness and pain was reappeared. MRI showed large amount of
epidural fluid collection. We performed wound revision and there was large amount
of gelatinous fluid at the epidural space. We suggest that postoperative mucin
collection and wound problems should be considered after surgery for mucin
producing metastatic pancreatic tumor.
PMID- 28407705
TI - Delayed Spondylodiscitis Presenting as a Skip Lesion.
AB - Spondylodiscitis is believed to be caused by an infection that affects vertebral
bodies and the intervening intervertebral disc. Usually, typical spondylodiscitis
involves a mobile vertebra-disc-vertebra unit, and in most cases, the condition
is managed successfully by surgical intervention and intravenous antibiotic
therapy. Here, the authors report an unusual case of a spondylodiscitis
presenting as a skip lesion, which progressed from L4/L5 to L1/L2, despite open
surgical biopsy and empirical intravenous antibiotics. Possible pathogenic
mechanisms of this unique case are discussed and a review of the pertinent
literature is included.
PMID- 28407706
TI - Gas-Containing Cervical Epidural Abscess Accompanying Bacterial Meningitis in an
Adult.
AB - Gas-containing spinal epidural abscesses are uncommon. Moreover, acute spinal
epidural abscesses rarely complicate bacterial meningitis in adults. Here, we
report a rare case of a gas-containing cervical epidural abscess accompanying
bacterial meningitis. In spite of aggressive fluid and continuous antibiotic
therapy after the isolation of Streptococcus anginosus and Streptococcus
constellatus in the cerebrospinal fluid cultures, the patient showed remaining
motor dysfunction and bladder involvement. Our experience suggests that the
effort to prevent neurologic deterioration by emergent surgical decompression and
drainage of pus is mandatory to avoid additional spinal cord dysfunction in
patients with spinal epidural abscesses accompanying bacterial meningitis.
PMID- 28407707
TI - Destruction of the C2 Body due to Cervical Actinomycosis: Connection between
Spinal Epidural Abscess and Retropharyngeal Abscess.
AB - Human actinomycosis with involvement of the spine is a rare condition, with only
a limited number of case reports published. To the best of our knowledge, no
cases have been reported of epidural abscess causing destruction of the C2 body,
bringing about a direct connection between spinal epidural and retropharyngeal
abscesses. Here, we present such a case that occurred after acupuncture, and we
review the relevant literature.
PMID- 28407708
TI - Application of Lateral Approach for the Removal of Migrated Interbody Cage:
Taphole and Fixing Technique.
AB - When a revision surgery related with removal of failed interbody cage is
required, going through the previous passage can lead to a higher risk of
neurological deficits or incidental dural injuries. Recently, the lateral
approach has become a popular method instead of the conventional anterior or
posterior approaches. The lateral approach is also useful method to remove failed
interbody cage previously placed and re-do interbody fusion with lower risks
compared to revision surgery via previous passage. However, there is still some
difficulty in retrieving the interbody cage from the intervertebral space because
of no spacious passage, subsidence, and uncontrolled movable cage. In this study,
we introduce our experience that we removed failed interbody cage more easily
with only the simple additional steps of making a taphole and fixing the cage
using a thread-tipped stick.
PMID- 28407709
TI - Synergistic antitumor effect of ING4/PTEN double tumor suppressors mediated by
adenovirus modified with RGD on glioma.
AB - BACKGROUND: Gene therapy is regarded as a new and promising therapeutic modality
for cancers, and adenovirus is one of the most frequently used vectors. However,
because of low or absent coxsackievirus and adenovirus receptor levels on the
surface of many kinds of tumor cells, the efficiency of adenovirus infection of
target tumor cells may be low. Meanwhile, gene therapy by a single vector
carrying two or more anti-oncogenes can improve treatment effects and reduce side
effects from vectors. In this research, we aimed to detect the anti-tumor effect
of ING4/PTEN double tumor suppressors mediated by adenovirus modified with
arginine(R)-glycine(G)-aspartate(D) (RGD) on glioma cells. METHODS: We treated
U87 glioma cells with PBS, blank adenovirus or adenovirus carrying RGD, ING4,
PTEN, or both ING4 and PTEN, then we detected and compared the U87 cells' growth,
apoptosis, and invasion. Moreover, we established a U87 glioma transplantation
tumor model to study the anti-tumor effect in vivo by measuring the volume and
weight of tumor masses in each condition. In addition, we analyzed the
transcription of related genes by fluorescent quantitative PCR and detected their
expression by immunohistochemistry staining to reveal the underlying mechanisms.
RESULTS: The double tumor suppressors ING4/PTEN could inhibit the growth of U87
glioma cells with a synergistic antitumor effect, and the RGD modification also
acted as an anti-oncogene to inhibit U87 cell invasion and tumor angiogenesis.
CONCLUSIONS: The ING4/PTEN double tumor suppressors mediated by adenovirus
modified with RGD had a significantly synergistic antitumor effect on glioma.
PMID- 28407710
TI - Generation of Triplet Excited States via Photoinduced Electron Transfer in meso
anthra-BODIPY: Fluorogenic Response toward Singlet Oxygen in Solution and in
Vitro.
AB - Heavy atom-free BODIPY-anthracene dyads (BADs) generate locally excited triplet
states by way of photoinduced electron transfer (PeT), followed by recombination
of the resulting charge-separated states (CSS). Subsequent quenching of the
triplet states by molecular oxygen produces singlet oxygen (1O2), which reacts
with the anthracene moiety yielding highly fluorescent species. The steric demand
of the alkyl substituents in the BODIPY subunit defines the site of 1O2 addition.
Novel bis- and tetraepoxides and bicyclic acetal products, arising from
rearrangements of anthracene endoperoxides were isolated and characterized. 1O2
generation by BADs in living cells enables visualization of the dyads
distribution, promising new imaging applications.
PMID- 28407711
TI - Using Ring Strain to Control 4pi-Electrocyclization Reactions: Torquoselectivity
in Ring Closing of Medium-Ring Dienes and Ring Opening of Bicyclic Cyclobutenes.
AB - Syntheses of strained cyclic dienes were accomplished via palladium(II)-catalyzed
oxidative cyclizations of terminal bis(vinylboronate esters). The reactions
generate strained (E,E)-1,3-dienes that undergo spontaneous 4pi
electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes
is driven by the strain in the medium-ring (E,E)-1,3-diene intermediate. Thermal
ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for
thermodynamic reasons. DFT calculations verified the thermodynamic versus kinetic
control of the reactions, and kinetic studies are in excellent agreement with the
calculated energy changes. An extension of the tandem coupling/4pi
electrocyclization pathway was demonstrated by a palladium(II)-catalyzed
oxidative homocoupling/8pi-electrocyclization cascade.
PMID- 28407712
TI - Relationship between Young's Modulus and Film Architecture in Cellulose
Nanofibril-Based Multilayered Thin Films.
AB - Young's moduli of cellulose nanofibril (CNF)-poly(allylamine hydrochloride) (PAH)
multilayered thin films were measured using strain-induced elastic buckling
instability for mechanical measurements (SIEBIMM) and the quantitative
nanomechanical mapping technique (PF-QNM). To establish the relationship between
structure and mechanical properties, three types of films with various
architectures were built using the layer-by-layer method by changing the ionic
strength of the dipping solution. Both methods demonstrate that the architecture
of a film has a strong impact on its mechanical properties even though the film
has similar cellulose content, emphasizing the role of the architecture. Films
with lower porosity (Phiair = 0.34) and a more intricate network display the
highest Young's moduli (9.3 GPa), whereas others with higher and similar porosity
(Phiair = 0.46-0.48) present lower Young's moduli (4.0-5.0 GPa). PF-QNM
measurements indicate a reverse ranking that is probably indicative of the
surface composition of the films.
PMID- 28407713
TI - Bifunctional Quaternary Ammonium Salts Catalyzed Stereoselective Conjugate
Addition of Oxindoles to Electron-Deficient beta-Haloalkenes.
AB - A highly Z-selective asymmetric conjugate addition of 3-substituted oxindoles to
beta-haloalkene ketones/esters catalyzed by readily available chiral bifunctional
quaternary ammonium salts is reported. This reaction provides efficient access to
a range of 2-oxoindole derivatives bearing a thermodynamically unstable Z-olefin
structure and a chiral quaternary carbon center in high yields (up to 90%) and
with good to high stereoselectivities (up to >19:1 Z/E and 91% ee) under mild
conditions.
PMID- 28407714
TI - Three-Body Fragmentation from Single Ionization of Water by Electron Impact: The
Role of Satellite States.
AB - Ionization of water with energy transfers close to the 2a1 inner valence orbital
is accompanied by a fast electronic rearrangement driven by electron relaxation
and electron-electron correlations. Quasi-degenerate single vacancy and
satellites one-electron-two-vacancies excited states in outer shells are created
and leave their fingerprints in the three-body fragmentation pattern. Single
vacancy states have been associated with Auger decay and double ionization.
Satellite excited states are here convincingly assigned to single ionization. We
focus on the H0 + O+ + H0 fragmentation by electron impact taking advantage of
the high sensitivity of the delayed extraction time-of-flight technique to
uncover kinematic attributes of suprathermal O+ ions. It is found that the H0
ejections occur under a large angular rearrangement, in an approximate linear
geometry, and leaving the O+ near at rest, with ~50% of the O+ produced in water
fragmentation by swift electrons presenting this feature.
PMID- 28407716
TI - Killing of bacteria by copper, cadmium, and silver surfaces reveals relevant
physicochemical parameters.
AB - The killing of bacteria on metallic copper surfaces in minutes to hours is
referred to as contact killing. Why copper possesses such strong antimicrobial
activity has remained enigmatic. Based on the physicochemical properties of
metals, it was recently predicted that cadmium should also be active in contact
killing [Hans et al., Biointerphases 11, 018902 (2010)]. Here, the authors show
that cadmium is indeed antimicrobial. It kills three logs of bacteria in 9 h,
compared to copper which kills eight logs of bacteria. Metallic silver kills less
than one log of bacteria in 9 h. These findings support the novel concept whereby
oxide formation, metal ion dissolution, and a Pearson soft character are the key
factors for a metal to be antibacterial. Based on these parameters, copper and
cadmium are expected to be the two most antibacterial metals.
PMID- 28407717
TI - The impact of insertion sequences on bacterial genome plasticity and
adaptability.
AB - Transposable elements (TE), small mobile genetic elements unable to exist
independently of the host genome, were initially believed to be exclusively
deleterious genomic parasites. However, it is now clear that they play an
important role as bacterial mutagenic agents, enabling the host to adapt to new
environmental challenges and to colonize new niches. This review focuses on the
impact of insertion sequences (IS), arguably the smallest TE, on bacterial genome
plasticity and concomitant adaptability of phenotypic traits, including
resistance to antibacterial agents, virulence, pathogenicity and catabolism. The
direct consequence of IS transposition is the insertion of one DNA sequence into
another. This event can result in gene inactivation as well as in modulation of
neighbouring gene expression. The latter is usually mediated by de-repression or
by the introduction of a complete or partial promoter located within the element.
Furthermore, transcription and transposition of IS are affected by host factors
and in some cases by environmental signals offering the host an adaptive strategy
and promoting genetic variability to withstand the environmental challenges.
PMID- 28407718
TI - Perspectives on tactile intervention for children with cerebral palsy: a
framework to guide clinical reasoning and future research.
AB - PURPOSE: Many children with cerebral palsy (CP) are known to experience tactile
impairments. Research evaluating specific interventions to manage this is,
however, minimal. This paper seeks to consolidate current literature and provide
a framework to help clinicians and researchers think strategically about tactile
treatment selection and future research planning. METHOD: The framework is
described via a novel analogy - "The Apartment Block Theory". The theory
describes the relative effectiveness of three intervention strategies aimed at
overcoming a poorly responsive tactile system: (1) Pressing the buzzer -
providing repeated passive tactile stimulation at the periphery; (2) Sneaking in
the door - providing active tactile-enhanced motor training that capitalises on
the opportunity to provide high-dose tactile input during motor interventions;
and (3) Connecting another way - providing visually enhanced touch strategies
with the aim of enhancing tactile function, which can be compared to phoning the
apartment as an alternative to using the buzzer. RESULTS: Using this theory, the
paper describes which sub-groups of children with CP may benefit from each
intervention strategy when considering their capabilities in visual, motor, and
attention domains. CONCLUSIONS: This theory can assist clinicians to provide
effective interventions and researchers to make informed future research
decisions to optimise tactile function for children with CP. Implications for
Rehabilitation Although tactile impairments are reported to be common in children
with cerebral palsy, very few successful interventions are reported in the
literature. Visually enhanced touch is a successful strategy for treating tactile
impairments in children with cerebral palsy who have sufficient vision and
attention. Combining intentional tactile input with upper limb movement training
may improve tactile function in children with cerebral palsy who have sufficient
movement and attention. In children who have complex co-morbidities, including
both visual and movement impairments, it may be necessary to consider providing
passive tactile stimulation in tactile intervention.
PMID- 28407719
TI - Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in
human dermal fibroblasts.
AB - CONTEXT: Clove (Eugenia caryophyllata Thunb. [Myrtaceae]) essential oil (CEO) has
been shown to possess antimicrobial, antifungal, antiviral, antioxidant, anti
inflammatory and anticancer properties. However, few studies have focused on its
topical use. OBJECTIVE: We investigated the biological activity of a commercially
available CEO in a human skin disease model. MATERIALS AND METHODS: We evaluated
the effect of CEO on 17 protein biomarkers that play critical roles in
inflammation and tissue remodelling in a validated human dermal fibroblast
system, which was designed to model chronic inflammation and fibrosis. Four
concentrations of CEO (0.011, 0.0037, 0.0012, and 0.00041%, v/v) were studied.
The effect of 0.011% CEO on genome-wide gene expression was also evaluated.
RESULTS AND DISCUSSION: CEO at a concentration of 0.011% showed robust
antiproliferative effects on human dermal fibroblasts. It significantly inhibited
the increased production of several proinflammatory biomarkers such as vascular
cell adhesion molecule-1 (VCAM-1), interferon gamma-induced protein 10 (IP-10),
interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced
by gamma interferon (MIG). CEO also significantly inhibited tissue remodelling
protein molecules, namely, collagen-I, collagen-III, macrophage colony
stimulating factor (M-CSF), and tissue inhibitor of metalloproteinase 2 (TIMP-2).
Furthermore, it significantly modulated global gene expression and altered
signalling pathways critical for inflammation, tissue remodelling, and cancer
signalling processes. CEO significantly inhibited VCAM-1 and collagen III at both
protein and gene expression levels. CONCLUSIONS: This study provides important
evidence of CEO-induced anti-inflammatory and tissue remodelling activity in
human dermal fibroblasts. This study also supports the anticancer properties of
CEO and its major active component eugenol.
PMID- 28407720
TI - Cross-cultural adaptation and validation of the Arabic version of the knee
outcome survey-activities for daily living scale.
AB - PURPOSE: The purpose of this study is to cross-culturally adapt the Knee Outcome
Survey-Activities of Daily Living Scale into Arabic and to assess its
psychometric properties (internal consistency, reliability, validity, and
responsiveness) in patients with knee disorders. METHODS: The cross-cultural
adaptation process for the Knee Outcome Survey-Activities of Daily Living Scale
into Arabic was performed consistent with the published guidelines. The
psychometric properties of this Arabic version were then evaluated. Participants
completed this version three times: at baseline, 2-4 days later, and 4 weeks
later. Correlations between the Arabic version of Knee Outcome Survey-Activities
of Daily Living Scale and the Arabic version of the Short Form-36 Health Survey,
Get Up and Go, and Ascending/Descending stairs tests were evaluated. RESULTS:
Linguistic and cultural issues were addressed. The Arabic version of the Knee
Outcome Survey-Activities of Daily Living Scale demonstrated excellent internal
consistency (Cronbach's alpha = 0.97) and excellent test-retest reliability
(intraclass correlation coefficient = 0.97). Construct validity of the Arabic
version of the Knee Outcome Survey-Activities of Daily Living Scale with the
Arabic version of Short Form-36 Health Survey subscales ranged from r = 0.28 to
0.53, p < 0.001. Criterion validity with the Get Up and Go and
Ascending/Descending stairs tests ranged from r = -0.47 to -0.60, p < 0.01. This
Arabic version was able to detect changes 4 weeks later (effect size = 1.12 and
minimum clinically important difference = 14 points). CONCLUSIONS: The Arabic
version of the Knee Outcome Survey-Activities of Daily Living Scale is a
reliable, valid and responsive measure for assessing knee-related symptoms and
functional limitations Implications for rehabilitation The Knee Outcome Survey
Activities of Daily Living Scale-Arabic is a reliable, valid and responsive
measure for assessing knee-related functional limitations. This Arabic version
can be used in clinical practice and for research purposes to assess symptoms and
functional limitations in Arabic-speaking patients with knee disorders. This
scale is responsive to track therapeutic outcome of Arabic-speaking patients with
knee disorders.
PMID- 28407721
TI - Chemical composition and biological investigation of Pelargonium endlicherianum
root extracts.
AB - CONTEXT: Pelargonium endlicherianum Fenzl. (Geraniaceae) roots and flowers are
traditionally used in Turkey as a decoction treatment against intestinal
parasites. Neither the chemical composition nor the potential bioactivity of the
plant roots has been studied before. OBJECTIVES: The phenolic content and effects
of P. endlicherianum root extracts on antioxidant enzyme levels on A549 cells
were studied for the first time. MATERIALS AND METHODS: The chemical composition
was analyzed via spectrophotometric and chromatographic (HPLC MS/MS and HPLC)
techniques. The antioxidant activity was determined at different concentrations
ranging from 0.001 to 2 mg/mL using DPPH* and ABTS*+ radical scavenging activity,
beta-carotene-linoleic acid co-oxidation assay, protection of 2-deoxyribose and
bovine brain-derived phospholipids against a hydroxyl radical-mediated
degradation assay. Glutathione peroxidase and superoxide dismutase activities
were also studied as well as the effects of the extracts on nitric oxide levels
on IL-1beta stimulated A549 cells. RESULTS: The key parameters for the most
active ethyl acetate extract included the following: DPPH* IC50: 0.23 mg/mL,
TEAC/ABTS: 2.17 mmol/L Trolox, reduction: 0.41 mmol/g AsscE, and protection of
lipid peroxidation IC50: 0.05 mg/mL. Furthermore, the ethyl acetate extract
increased the SOD level significantly compared to control group (4.48 U/mL) at
concentrations of 100 and 200 MUg/mL SOD, 5.50 and 5.67 U/mL, respectively.
Apocynin was identified as the major component, and the ethyl acetate fraction
was found to be rich in phenolic compounds. DISCUSSION AND CONCLUSION:
Pelargonium endlicherianum root extracts displayed antioxidant activity and
increased the antioxidant enzyme levels in IL-1beta stimulated A549 cells, while
decreasing the NO levels.
PMID- 28407722
TI - Induced hypothermia is associated with reduced circulating subunits of
mitochondrial DNA in cardiac arrest patients.
AB - Induced hypothermia may protect from ischemia reperfusion injury. The mechanism
of protection is not fully understood and may include an effect on mitochondria.
Here we describe the effect of hypothermia on circulating mitochondrial (mt) DNA
in a substudy of a multicenter randomized trial (the Target Temperature
Management trial). Circulating levels of mtDNA were elevated in patients with
cardiac arrest at all-time points compared to healthy controls. After 24 h of
temperature management, patients kept at 33 degrees C had significantly lower
levels of COX3, NADH1 and NADH2 compared to baseline, in contrast to those kept
at 36 degrees C. After regain of temperature, cytochrome - B was significantly
reduced in patients kept at 33 degrees C with cardiac arrest. Cardiac arrest
results in circulating mtDNA levels, which reduced during a temperature
management protocol in patients with a target temperature of 33 degrees C.
PMID- 28407723
TI - DNA barcodes and insights into the phylogenetic relationships of Corvidae (Aves:
Passeriformes).
AB - DNA barcoding has become a promising tool for species identification and
phylogeny in a wide range of animal taxa using mitochondrial cytochrome c oxidase
subunit I (COI). The Corvidae (Aves: Passeriformes) is a species rich and
morphologically diverse family. In the present study, we analyzed the COI
barcodes of 39 species from 12 genera of Corvidae. COI gene was also used to
examine phylogenetic relationships of Corvidae. Every species possessed a barcode
distinct from that of other species. Kimura two-parameter distances were
calculated between species barcodes. The average genetic distance between the
species was 22 times higher compared to the average genetic distance within
species. Maximum likelihood method was used to construct a phylogenetic tree. All
the species could be discriminated by their distinct clades in the phylogenetic
tree. COI gene data provided good evidence for the monophyly of the Corvidae.
Members of Cyanopica and Pyrrhocorax were the first to split from the Corvidae
lineage. Analysis of COI genes supported the others genera fell into two clades.
DNA barcoding is an effective molecular tool for Corvidae species identification
and phylogenetic inference.
PMID- 28407724
TI - Psychometric properties of the Norwegian self-efficacy for therapeutic mode use
(N-SETMU).
AB - BACKGROUND: According to the Intentional Relationship Model (IRM), the
intentional use of relational approaches in therapy (therapeutic modes) is
essential for obtaining successful relationships to clients. There have been no
attempts to combine the IRM with self-efficacy theory, and instruments for
measuring self-efficacy for therapeutic mode use are lacking. AIM: This study
aimed to examine the component structure and internal consistency of the
Norwegian version of the Self-Efficacy for Therapeutic Mode Use (N-SETMU).
METHODS: Occupational therapy students (n = 111) from two education programs
completed the N-SETMU along with sociodemographic information. Principal
Components Analysis (PCA) was performed and component extraction was controlled
using Parallel Analysis. Internal consistency was assessed with Cronbach's alpha
and inter-item correlations. RESULTS: All items on the N-SETMU loaded on the same
latent dimension, tentatively called Self-Efficacy for Therapeutic Mode Use.
Cronbach's alpha for the scale was 0.82. CONCLUSIONS: The N-SETMU is a
unidimensional measure of self-efficacy for therapeutic mode use in general. The
N-SETMU may be a useful tool for occupational therapy research and audits
focusing on occupational therapists' use of therapeutic modes in client
interactions.
PMID- 28407725
TI - Experiences of hospital readmission and receiving formal carer services following
spinal cord injury: a qualitative study to identify needs.
AB - PURPOSE: The purpose of this study is to explore the needs of people living with
spinal cord injury, receiving formal carer and hospital services. MATERIALS AND
METHODS: This exploratory qualitative study was undertaken with people living
with spinal cord injury in metropolitan or regional Victoria. Participants were
recruited through the Australian Quadriplegic Association. Twenty-two in-depth
interviews were conducted between September and October 2015. Participants were
purposely selected based on their age, gender, level of injury, and compensation
status. A thematic analysis was undertaken using a framework approach. RESULTS
AND CONCLUSIONS: With respect to hospitalization, the findings highlighted the
need for improved access to spinal cord injury specialist care and greater
personalization of care delivery for people with spinal cord injury. When
receiving formal care services, participants reported the need for carers to be
educated in preventing and managing secondary conditions, and for information
about managing carers in their life and home. A more reliable and accessible
supply of carers was also required to reduce the anxiety associated with an
actual or potential absence of their assistance. To improve the independence and
quality of care and life for people living with spinal cord injury, more
responsive and individualized care is needed in the hospital, rehabilitation, and
community settings. Implications for rehabilitation Understanding the
individualized needs of people living with spinal cord injury and their families
with respect to carer management is necessary to provide tailored rehabilitation
education and ensure appropriate community supports are in place. The development
of individualized plans by rehabilitation health professionals for obtaining
spinal cord injury specialist care post-discharge could reduce anxiety and
improve safety and quality of care. Integrating peer support into rehabilitation
processes could offer benefits in managing carer issues. Greater family
involvement in the rehabilitation process and follow-up psychological support
could assist with adjustment and quality of life post-discharge.
PMID- 28407726
TI - Complementary Features of Attention Bias Modification Therapy and Cognitive
Behavioral Therapy in Pediatric Anxiety Disorders.
AB - OBJECTIVE: In the treatment of anxiety disorders, attention bias modification
therapy (ABMT) and cognitive-behavioral therapy (CBT) may have complementary
effects by targeting different aspects of perturbed threat responses and
behaviors. ABMT may target rapid, implicit threat reactions, whereas CBT may
target slowly deployed threat responses. The authors used amygdala-based
connectivity during a threat-attention task and a randomized controlled trial
design to evaluate potential complementary features of these treatments in
pediatric anxiety disorders. METHOD: Prior to treatment, youths (8-17 years old)
with anxiety disorders (N=54), as well as healthy comparison youths (N=51),
performed a threat-attention task during functional MRI acquisition. Task-related
amygdala-based functional connectivity was assessed. Patients with and without
imaging data (N=85) were then randomly assigned to receive CBT paired with either
active or placebo ABMT. Clinical response was evaluated, and pretreatment
amygdala-based connectivity profiles were compared among patients with varying
levels of clinical response. RESULTS: Compared with the CBT plus placebo ABMT
group, the CBT plus active ABMT group exhibited less severe anxiety after
treatment. The patient and healthy comparison groups differed in amygdala-insula
connectivity during the threat-attention task. Patients whose connectivity
profiles were most different from those of the healthy comparison group exhibited
the poorest response to treatment, particularly those who received CBT plus
placebo ABMT. CONCLUSIONS: The study provides evidence of enhanced clinical
effects for patients receiving active ABMT. Moreover, ABMT appears to be most
effective for patients with abnormal amygdala-insula connectivity. ABMT may
target specific threat processes associated with dysfunctional amygdala-insula
connectivity that are not targeted by CBT alone. This may explain the observation
of enhanced clinical response to CBT plus active ABMT.
PMID- 28407727
TI - Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major
Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall.
AB - OBJECTIVE: Patients with depression show blunted amygdala hemodynamic activity to
positive stimuli, including autobiographical memories. The authors examined the
therapeutic efficacy of real-time functional MRI neurofeedback (rtfMRI-nf)
training aimed at increasing the amygdala's hemodynamic response to positive
memories in patients with depression. METHOD: In a double-blind, placebo
controlled, randomized clinical trial, unmedicated adults with depression (N=36)
were randomly assigned to receive two sessions of rtfMRI-nf either from the
amygdala (N=19) or from a parietal control region not involved in emotional
processing (N=17). Clinical scores and autobiographical memory performance were
assessed at baseline and 1 week after the final rtfMRI-nf session. The primary
outcome measure was change in score on the Montgomery-Asberg Depression Rating
Scale (MADRS), and the main analytic approach consisted of a linear mixed-model
analysis. RESULTS: In participants in the experimental group, the hemodynamic
response in the amygdala increased relative to their own baseline and to the
control group. Twelve participants in the amygdala rtfMRI-nf group, compared with
only two in the control group, had a >50% decrease in MADRS score. Six
participants in the experimental group, compared with one in the control group,
met conventional criteria for remission at study end, resulting in a number
needed to treat of 4. In participants receiving amygdala rtfMRI-nf, the percent
of positive specific memories recalled increased relative to baseline and to the
control group. CONCLUSIONS: rtfMRI-nf training to increase the amygdala
hemodynamic response to positive memories significantly decreased depressive
symptoms and increased the percent of specific memories recalled on an
autobiographical memory test. These data support a role of the amygdala in
recovery from depression.
PMID- 28407728
TI - Long-lasting improvements in health-related quality of life among women with
chronic pain, following multidisciplinary rehabilitation.
AB - PURPOSE: To determine whether observed health-related quality-of-life
improvements after four-week traditional multidisciplinary pain management
program and additional neuroscience education and mindfulness-based cognitive
therapy for chronic pain are sustained at six-month follow-up. METHOD: This
observational longitudinal follow-up study, with complete follow-up of 75 women,
61.5% of initial traditional approach group (treated 2001-2005) and 56 (62.2%)
receiving the new approach (treated 2006-2009). Pain intensity and quality of
life were measured at baseline and six months after interventions. Analysis of
variance (ANOVA) and paired samples t-tests were used for statistical analysis.
RESULTS: Both groups showed sustained improvements in pain intensity (traditional
approach = -10.6 [p < 0.001]; new approach = -14.5 [p < 0.001]) and quality of
life (traditional approach = 6.4 [p < 0.001]; new approach = 6.9 [p < 0.001]).
Sleep was not sustained among traditional approach group (change = 2.4 [p =
0.066]), whereas all other domains among both groups were sustained. Significant
decline was observed from discharge to six month among both groups with the
exception of the sleep domain among the traditional approach group, pain
intensity among the new approach and financial status among both groups. No
baseline differences were revealed between responders and nonresponders.
CONCLUSIONS: Multidisciplinary interventions for women with chronic pain
conditions improved quality of life and pain intensity with lasting improvements
observed half a year after treatment completion. Implications for rehabilitation
Intensive multidisciplinary biopsychosocial rehabilitation is essential for
chronic pain conditions. This follow-up study shows sustained improvement in
health-related quality of life and pain intensity six months after such
rehabilitation was completed. Emphasizing mindfulness-based cognitive therapy and
neuroscience patient education may contribute to less decline in pain intensity
from discharge to six-month follow-up compared with a more traditional approach.
PMID- 28407729
TI - Corrigendum.
PMID- 28407730
TI - Men who have sex with men with newly-diagnosed HIV are often eligible for HIV pre
exposure prophylaxis.
PMID- 28407731
TI - Segmentum: a tool for copy number analysis of cancer genomes.
AB - BACKGROUND: Somatic alterations, including loss of heterozygosity, can affect the
expression of oncogenes and tumor suppressor genes. Whole genome sequencing
enables detailed characterization of such aberrations. However, due to the
limitations of current high throughput sequencing technologies, this task remains
challenging. Hence, accurate and reliable detection of such events is crucial for
the identification of cancer-related alterations. RESULTS: We introduce a new
tool called Segmentum for determining somatic copy numbers using whole genome
sequencing from paired tumor/normal samples. In our approach, read depth and B
allele fraction signals are smoothed, and double sliding windows are used to
detect breakpoints, which makes our approach fast and straightforward. Because
the breakpoint detection is performed simultaneously at different scales, it
allows accurate detection as suggested by the evaluation results from simulated
and real data. We applied Segmentum to paired tumor/normal whole genome
sequencing samples from 38 patients with low-grade glioma from the TCGA dataset
and were able to confirm the recurrence of copy-neutral loss of heterozygosity in
chromosome 17p in low-grade astrocytoma characterized by IDH1/2 mutation and lack
of 1p/19q co-deletion, which was previously reported using SNP array data.
CONCLUSIONS: Segmentum is an accurate, user-friendly tool for somatic copy number
analysis of tumor samples. We demonstrate that this tool is suitable for the
analysis of large cohorts, such as the TCGA dataset.
PMID- 28407732
TI - Transcriptome profiling reveals expression signatures of cranial neural crest
cells arising from different axial levels.
AB - BACKGROUND: Cranial neural crest cells (NCCs) are a unique embryonic cell type
which give rise to a diverse array of derivatives extending from neurons and glia
through to bone and cartilage. Depending on their point of origin along the
antero-posterior axis cranial NCCs are rapidly sorted into distinct migratory
streams that give rise to axial specific structures. These migratory streams
mirror the underlying segmentation of the brain with NCCs exiting the
diencephalon and midbrain following distinct paths compared to those exiting the
hindbrain rhombomeres (r). The genetic landscape of cranial NCCs arising at
different axial levels remains unknown. RESULTS: Here we have used RNA sequencing
to uncover the transcriptional profiles of mouse cranial NCCs arising at
different axial levels. Whole transcriptome analysis identified over 120
transcripts differentially expressed between NCCs arising anterior to r3
(referred to as r1-r2 migratory stream for simplicity) and the r4 migratory
stream. Eight of the genes differentially expressed between these populations
were validated by RT-PCR with 2 being further validated by in situ hybridisation.
We also explored the expression of the Neuropilins (Nrp1 and Nrp2) and their co
receptors and show that the A-type Plexins are differentially expressed in
different cranial NCC streams. CONCLUSIONS: Our analyses identify a large number
of genes differentially regulated between cranial NCCs arising at different axial
levels. This data provides a comprehensive description of the genetic landscape
driving diversity of distinct cranial NCC streams and provides novel insight into
the regulatory networks controlling the formation of specific skeletal elements
and the mechanisms promoting migration along different paths.
PMID- 28407734
TI - The inverse effect of meal intake on controlled attenuation parameter and liver
stiffness as assessed by transient elastography.
AB - BACKGROUND: Controlled attenuation parameter (CAP) and liver stiffness (LS)
measured by transient elastography (TE, Fibroscan(r)) have been used for
steatosis and fibrosis assessment. We evaluated the effect of meal intake on CAP
and LS values. METHODS: Forty patients who had had a liver biopsy within the
previous month were recruited. The biopsy was graded for fibrosis (F) and
steatosis (S) stagings. TE was performed after overnight fasting (baseline
values) and 15, 30, 45, 60, 90, and 120 min following the intake of a standard
commercial formula meal, and every 30 min until LS and CAP values returned to
baseline. The effect of meal intake on CAP and LS values was analyzed with a
multilevel mixed model approach. RESULTS: The mean age was 53.1 +/- 11.2 years
old. The mean (SD) BMI was 25.6 +/- 4.5 kg/m2. F0, F1, F2, F3 and F4 fibrosis
stages were found in 17 (42.5%), 9 (22.5%), 4 (10.0%), 8 (20.0%) and 2 (5.0%),
respectively. S0, S1, S2 and S3 steatosis stages were seen in 22 (55.0%), 11
(27.5%), 4 (10.0%) and 3 (7.5%), respectively. The mean (SD) CAP and median (IQR)
LS values at baseline were 249.7 +/- 58.1 dB/m and 11.9 (6-18.1) kPa. A
significant decrease in CAP values was observed in all patients 15 to 120 min
after meals, with the CAP peak value at 60 min and the mean post-meal delta
reduction of 18.1 dB/min. CAP values declined after meals at early fibrosis
stages and across all stages of steatosis. A significant increase in LS values
after meal intake was observed within 15 to 120 min, with the LS peak value at 15
min and the mean post-meal delta increase of 2.4 kPa. Post-meal CAP and LS values
returned to baseline within 150 min following meals. CONCLUSION: Following a
meal, patients' CAP values declined with the peak value at 60 min, contrasting
with the rising of LS values with the peak value at 15 min. The post-meal CAP and
LS values returned to baseline by 150 min. A fasting period of more than 150 min
after a meal is recommended for patients undergoing TE.
PMID- 28407733
TI - The Kruppel-like factor 9 cistrome in mouse hippocampal neurons reveals
predominant transcriptional repression via proximal promoter binding.
AB - BACKGROUND: Kruppel-like factor 9 (Klf9) is a zinc finger transcription factor
that functions in neural cell differentiation, but little is known about its
genomic targets or mechanism of action in neurons. RESULTS: We used the mouse
hippocampus-derived neuronal cell line HT22 to identify genes regulated by Klf9,
and we validated our findings in mouse hippocampus. We engineered HT22 cells to
express a Klf9 transgene under control of the tetracycline repressor, and used
RNA sequencing to identify genes modulated by Klf9. We found 217 genes repressed
and 21 induced by Klf9. We also engineered HT22 cells to co-express biotin ligase
and a Klf9 fusion protein containing an N-terminal biotin ligase recognition
peptide. Using chromatin-streptavidin precipitation (ChSP) sequencing we
identified 3,514 genomic regions where Klf9 associated. Seventy-five percent of
these were within 1 kb of transcription start sites, and Klf9 associated in
chromatin with 60% of the repressed genes. We analyzed the promoters of several
repressed genes containing Klf9 ChSP peaks using transient transfection reporter
assays and found that Klf9 repressed promoter activity, which was abolished after
mutation of Sp/Klf-like motifs. Knockdown or knockout of Klf9 in HT22 cells
caused dysregulation of Klf9 target genes. Chromatin immunoprecipitation assays
showed that Klf9 associated in chromatin from mouse hippocampus with genes
identified by ChSP sequencing on HT22 cells, and expression of Klf9 target genes
was dysregulated in the hippocampus of neonatal Klf9-null mice. Gene ontology
analysis revealed that Klf9 genomic targets include genes involved in
cystokeletal remodeling, Wnt signaling and inflammation. CONCLUSIONS: We have
identified genomic targets of Klf9 in hippocampal neurons and created a
foundation for future studies on how it functions in chromatin, and regulates
neuronal morphology and survival across the lifespan.
PMID- 28407736
TI - Large enchondroma of the thoracic spine: a rare case report and review of the
literature.
AB - BACKGROUND: Enchondroma, a subtype of chondroma, originates from the medullary
cavity of the bone and produces an expansile growth pattern. Enchondroma located
in the spine is rare and a few cases of large thoracic enchondroma have been
reported. The authors document a rare case of large enchondroma in the thoracic
spine of a 49-year-old woman, and discuss its clinical, radiological and
histopathological characteristics. CASE PRESENTATION: The patient presented with
rapidly progressive and severe pain on her upper back. Magnetic resonance imaging
revealed an expansile lesion at the posterior elements of T3 that was hypointense
on T1-weighted images and mixed iso- to hyperintense on T2-weighted images.
Administration of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)
resulted in heterogeneous enhancement. During surgery, a large tumor of 4.2cm *
4.7cm * 2.1cm was resected along with the lamina and spinous process.
Histological examination revealed that the tumor consisted of mature hyaline
cartilage with typical chondrocytes, indicating that it was an enchondroma.
CONCLUSIONS: Despite its benign-growing nature, enchondroma should be examined
closely for signs of enchondromatosis and enchondrosarcoma. Complete surgical
resection is the treatment of choice for immediate relief of symptoms and
avoidance of recurrence.
PMID- 28407735
TI - Telbivudine treatment started in early and middle pregnancy completely blocks HBV
vertical transmission.
AB - BACKGROUND: To evaluate the efficacy and safety of treating HBV-positive mothers
with telbivudine in early and middle pregnancy to prevent mother-to-infant HBV
transmission. METHODS: The subject population comprised pregnant women with
chronic hepatitis B (CHB; n = 188) from January 2013 to June 2015, with HBV DNA
>=1.0 * 107copies/mL and increased alanine aminotransferase levels. Groups A (n =
62) and B (n = 61) were treated with telbivudine starting at 12 weeks or 20-28
weeks after gestation, respectively. Telbivudine was discontinued at postpartum
12 weeks. Group C (n = 65) received no antiviral. All infants were vaccinated
with hepatitis B immunoglobulin (200 IU) and HBV vaccine (20 with hepatitis B The
maternal HBV DNA levels of the groups were compared. Mother-to-infant
transmission of HBV was indicated by the presence of HBsAg in infants 7 months
after birth. RESULTS: Before treatment, the HBV DNA levels of the 3 groups were
similar. Before delivery and 12 weeks after delivery, the HBV DNA levels of
groups A and B were similar, but both were significantly lower than that of group
C (P < 0.01, all). No infants in groups A and B were HBsAg-positive, but the
infection rate of group C was 18.4% (P < 0.01). The HBV infection rate of infants
was positively associated with the HBV DNA levels of the pregnant mothers.
CONCLUSION: Administration of telbivudine to HBV-infected mothers, started during
early and middle pregnancy, completely blocked mother-to-infant HBV transmission.
TRIAL REGISTRATION: The study was registered retrospectively on Janurary 25 in
2016 at Chinese Clinical Trial Registry ( ChiCTR-OPC-16007899 ).
PMID- 28407737
TI - Pain in amaXhosa women living with HIV/AIDS: a cross-sectional study of ambulant
outpatients.
AB - BACKGROUND: Pain is one of the most commonly reported symptoms in people living
with HIV/AIDS, whether or not they are receiving anti-retroviral therapy. A
recent systematic review identified a paucity of studies exploring pain in women
in low and middle income countries. The prevalence and characteristics of pain in
women living with HIV/AIDS may differ from that of men as many chronic pain
conditions are more prevalent in women. The aims of this study were to establish
pain prevalence, characteristics and management in amaXhosa women living with
HIV/AIDS. In addition, we aimed to identify whether there were associations
between pain in this population and the psychosocial factors of employment,
education, self-efficacy, depression, post-traumatic stress disorder, health
related quality of life and childhood trauma. METHODS: A cross-sectional study of
229 women who had undergone HIV testing and were registered patients at a
community health centre was conducted. Data were collected by interview with a
demographic questionnaire, the Brief Pain Inventory-Xhosa, Childhood Trauma
Questionnaire-Xhosa, Harvard Trauma Questionnaire-Xhosa for PTSD, Self-Efficacy
for Managing Chronic Disease 6-Item Scale-Xhosa; the EQ-5D health related quality
of life instrument, and the Beck Depression Inventory. RESULTS: 170 of the women
had pain, a prevalence rate of 74.24% (95%CI 68.2 - 79.47%). The women reported
significant pain with pain severity of 5.06 +/- 1.57 and pain interference of
6.39 +/- 1.96 out of 10. Only two women were receiving adequate pain management
according to the pain management index. Participants reported a mean of 2.42 +/-
1.21 different anatomical sites of pain. There were more unemployed participants
in the group with pain and they had significantly fewer years of schooling. Those
with pain had lower self-efficacy; health related quality of life and increased
depression and PTSD symptom severity. CONCLUSION: This study highlights that pain
is a common problem for amaXhosa women living with HIV/AIDS. These data emphasise
the need to prioritise pain assessment and management in amaXhosa women living
with HIV/AIDS. Routinely assessing for the presence of pain in women with
HIV/AIDS has the potential to improve pain management and minimise the impact of
pain on function.
PMID- 28407738
TI - "Why won't they just vaccinate?" Horse owner risk perception and uptake of the
Hendra virus vaccine.
AB - BACKGROUND: Hendra virus is a paramyxovirus that causes periodic serious disease
and fatalities in horses and humans in Australia first identified in 1994.
Pteropid bats (commonly known as flying-foxes) are the natural host of the virus,
and the putative route of infection in horses is by ingestion or inhalation of
material contaminated by flying-fox urine or other bodily fluids. Humans become
infected after close contact with infected horses. Horse owners in Australia are
encouraged to vaccinate their horses against Hendra virus to reduce the risk of
Hendra virus infection, and to prevent potential transmission to humans. After
the vaccine was released in 2012, uptake by horse owners was slow, with some
estimated 11-17% of horses in Australia vaccinated. This study was commissioned
to examine barriers to vaccine uptake and potential drivers to future adoption of
vaccination by horse owners. METHODS: This study examined qualitative comments
from respondents to an on-line survey, reporting reasons for not vaccinating
their horses. The study also investigated scenarios in which respondents felt
they might consider vaccinating their horses. RESULTS: Self-reported barriers to
uptake of the Hendra virus vaccine by horse owners (N = 150) included concerns
about vaccine safety, cost, and effectiveness. Reduction in vaccination costs and
perception of immediacy of Hendra virus risk were reported as being likely to
change future behaviour. However, the data also indicated that horse owners
generally would not reconsider vaccinating their horses if advised by their
veterinarian. CONCLUSION: While changes to vaccine costs and the availability
data supporting vaccine safety and efficacy may encourage more horse owners to
vaccinate, this study highlights the importance of protecting the relationship
between veterinarians and horse owners within the risk management strategies
around Hendra virus. Interactions and trust between veterinarians and animal
owners has important implications for management of and communication around
Hendra virus and other zoonotic disease outbreaks.
PMID- 28407739
TI - Construction of a novel anaerobic pathway in Escherichia coli for propionate
production.
AB - BACKGROUND: Propionate is widely used as an important preservative and important
chemical intermediate for synthesis of cellulose fibers, herbicides, perfumes and
pharmaceuticals. Biosynthetic propionate has mainly been produced by
Propionibacterium, which has various limitations for industrial application.
RESULTS: In this study, we engineered E. coli by combining reduced TCA cycle with
the native sleeping beauty mutase (Sbm) cycle to construct a redox balanced and
energy viable fermentation pathway for anaerobic propionate production. As the
cryptic Sbm operon was over-expressed in E. coli MG1655, propionate titer reached
0.24 g/L. To increase precursor supply for the Sbm cycle, genetic modification
was made to convert mixed fermentation products to succinate, which slightly
increased propionate production. For optimal expression of Sbm operon, different
types of promoters were examined. A strong constitutive promoter Pbba led to the
highest titer of 2.34 g/L. Methylmalonyl CoA mutase from Methylobacterium
extorquens AM1 was added to strain T110(pbba-Sbm) to enhance this rate limiting
step. With optimized expression of this additional Methylmalonyl CoA mutase, the
highest production strain was obtained with a titer of 4.95 g/L and a yield of
0.49 mol/mol glucose. CONCLUSIONS: With various metabolic engineering strategies,
the propionate titer from fermentation achieved 4.95 g/L. This is the reported
highest anaerobic production of propionate by heterologous host. Due to host
advantages, such as non-strict anaerobic condition, mature engineering and
fermentation techniques, and low cost minimal media, our work has built the basis
for industrial propionate production with E. coli chassis.
PMID- 28407740
TI - Mu-opioid receptor and delta-opioid receptor differentially regulate microglial
inflammatory response to control proopiomelanocortin neuronal apoptosis in the
hypothalamus: effects of neonatal alcohol.
AB - BACKGROUND: Opioid receptors are known to control neurotransmission of various
peptidergic neurons, but their potential role in regulation of microglia and
neuronal cell communications is unknown. We investigated the role of mu-opioid
receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation
of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in
the hypothalamus. METHODS: Neonatal rat pups were fed a milk formula containing
ethanol or control diets between postnatal days 2-6. Some of the alcohol-fed rats
additionally received pretreatment of a microglia activation blocker minocycline.
Two hours after the last feeding, some of the pups were sacrificed and processed
for histochemical detection of microglial cell functions or confocal microscopy
for detection of cellular physical interaction or used for gene and protein
expression analysis. The rest of the pups were dissected for microglia separation
by differential gradient centrifugation and characterization by measuring
production of various activation markers and cytokines. In addition, primary
cultures of microglial cells were prepared using hypothalamic tissues of neonatal
rats and used for determination of cytokine production/secretion and apoptotic
activity of neurons. RESULTS: In the hypothalamus, neonatal alcohol feeding
elevated cytokine receptor levels, increased the number of microglial cells with
amoeboid-type circularity, enhanced POMC and microglial cell physical
interaction, and decreased POMC cell numbers. Minocycline reversed these cellular
effects of alcohol. Alcohol feeding also increased levels of microglia MOR
protein and pro-inflammatory signaling molecules in the hypothalamus, and MOR
receptor antagonist naltrexone prevented these effects of alcohol. In primary
cultures of hypothalamic microglia, both MOR agonist [D-Ala 2, N-MePhe 4, Gly-ol]
enkephalin (DAMGO) and ethanol increased microglial cellular levels and secretion
of pro-inflammatory cell signaling proteins. However, a DOR agonist [D
Pen2,5]enkephalin (DPDPE) increased microglial secretion of anti-inflammatory
cytokines and suppressed ethanol's ability to increase microglial production of
inflammatory signaling proteins and secretion of pro-inflammatory cytokines. In
addition, MOR-activated inflammation promoted while DOR-suppressed inflammation
inhibited the apoptotic effect of ethanol on POMC neurons. CONCLUSIONS: These
results suggest that ethanol's neurotoxic action on POMC neurons results from MOR
activated neuroinflammatory signaling. Additionally, these results identify a
protective effect of a DOR agonist against the pro-inflammatory and neurotoxic
action of ethanol.
PMID- 28407741
TI - The PD-1: PD-L1 pathway promotes development of brain-resident memory T cells
following acute viral encephalitis.
AB - BACKGROUND: Previous work from our laboratory has demonstrated that during acute
viral brain infection, glial cells modulate antiviral T cell effector responses
through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of
unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in
development of brain-resident memory T cells (bTRM) following murine
cytomegalovirus (MCMV) infection. METHODS: Flow cytometric analysis of immune
cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the
shift of brain-infiltrating CD8+ T cell populations from short-lived effector
cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of
bTRMs. RESULTS: In wild-type (WT) animals, we observed a switch in the phenotype
of brain-infiltrating CD8+ T cell populations from KLRG1+ CD127- (SLEC) to KLRG1-
CD127+ (MPEC) during transition from acute through chronic phases of infection.
At 14 and 30 dpi, the majority of CD8+ T cells expressed CD127, a marker of
memory cells. In contrast, fewer CD8+ T cells expressed CD127 within brains of
infected, PD-L1 knockout (KO) animals. Notably, in WT mice, a large population of
CD8+ T cells was phenotyped as CD103+ CD69+, markers of bTRM, and differences
were observed in the numbers of these cells when compared to PD-L1 KOs.
Immunohistochemical studies revealed that brain-resident CD103+ bTRM cells were
localized to the parenchyma. Higher frequencies of CXCR3 were also observed among
WT animals in contrast to PD-L1 KOs. CONCLUSIONS: Taken together, our results
indicate that bTRMs are present within the CNS following viral infection and the
PD-1: PD-L1 pathway plays a role in the generation of this brain-resident
population.
PMID- 28407742
TI - Higher neonatal growth rate and body condition score at 7 months are predictive
factors of obesity in adult female Beagle dogs.
AB - BACKGROUND: The risks during early growth on becoming overweight in adulthood are
widely studied in humans. However, early-life predictive factors for canine adult
overweight and obesity have not yet been studied. To identify factors that may
help explain the development of overweight and obesity at adulthood in dogs, a
longitudinal study of 2 years was conducted in 24 female Beagle dogs of the same
age, sexual status, and raised under identical environmental conditions. By means
of a hierarchical classification on principal components with the following
quantitative values: fat-free mass (FFM), percentage fat mass and pelvic
circumference at 2 years of age, three groups of dogs were established and were
nominally named: ideal weight (IW, n = 9), slightly overweight (OW1, n = 6) and
overweight (OW2, n = 9). With the aim of identifying predictive factors of
development of obesity at adulthood parental characteristics, growth pattern,
energy balance and plasma factors were analysed by logistic regression analysis.
RESULTS: At 24 months, the group compositions were in line with the body
condition scores (BCS 1-9) values of the IW (5 or 6/9), the OW1 (6/9) and the OW2
(7 or 8/9) groups. Logistic regression analysis permitted the identification of
neonatal growth rate during the first 2 weeks of life (GR2W) and BCS at 7 months
as predictors for the development of obesity at adulthood. Seventy percent of
dogs with either GR2W >125% or with BCS > 6/9 at 7 months belonged to the OW2
group. Results from energy intake and expenditure, corrected for FFM, showed that
there was a greater positive energy imbalance between 7 and 10 months for the
OW2, compared to the IW group. CONCLUSION: This study expands the understanding
of previously reported risk factors for being overweight or obese in dogs,
establishing that (i) 15 out of 24 of the studied dogs became overweight and (ii)
GR2W and BCS at 7 months of age could be used as predictive factors as overweight
adult dogs in the OW2 group had higher values compared the other groups of dogs.
PMID- 28407743
TI - New drugs, new toxicities: severe side effects of modern targeted and
immunotherapy of cancer and their management.
AB - Pharmacological and cellular treatment of cancer is changing dramatically with
benefits for patient outcome and comfort, but also with new toxicity profiles.
The majority of adverse events can be classified as mild or moderate, but severe
and life-threatening complications requiring ICU admission also occur. This
review will focus on pathophysiology, symptoms, and management of these events
based on the available literature.While standard antineoplastic therapy is
associated with immunosuppression and infections, some of the recent approaches
induce overwhelming inflammation and autoimmunity. Cytokine-release syndrome
(CRS) describes a complex of symptoms including fever, hypotension, and skin
reactions as well as lab abnormalities. CRS may occur after the infusion of
monoclonal or bispecific antibodies (MABs, BABs) targeting immune effectors and
tumor cells and is a major concern in recipients of chimeric antigen receptor
(CAR) modified T lymphocytes as well. BAB and CAR T-cell treatment may also be
compromised by central nervous system (CNS) toxicities such as encephalopathy,
cerebellar alteration, disturbed consciousness, or seizures. While CRS is known
to be induced by exceedingly high levels of inflammatory cytokines, the
pathophysiology of CNS events is still unclear. Treatment with antibodies against
inhibiting immune checkpoints can lead to immune-related adverse events (IRAEs);
colitis, diarrhea, and endocrine disorders are often the cause for ICU
admissions.Respiratory distress is the main reason for ICU treatment in cancer
patients and is attributable to infectious agents in most cases. In addition,
some of the new drugs are reported to cause non-infectious lung complications.
While drug-induced interstitial pneumonitis was observed in a substantial number
of patients treated with phosphoinositol-3-kinase inhibitors, IRAEs may also
affect the lungs.Inhibitors of angiogenetic pathways have increased the
antineoplastic portfolio. However, vessel formation is also essential for
regeneration and tissue repair. Therefore, severe vascular side effects,
including thromboembolic events, gastrointestinal bleeding or perforation,
hypertension, and congestive heart failure, compromise antitumor efficacy.The
limited knowledge of the pathophysiology and management of life-threatening
complications relating to new cancer drugs presents a need to provide ICU staff,
oncologists, and organ specialists with evidence-based algorithms.
PMID- 28407744
TI - Global Bi-ventricular endocardial distribution of activation rate during long
duration ventricular fibrillation in normal and heart failure canines.
AB - BACKGROUND: The objective of this study was to detect differences in the
distribution of the left and right ventricle (LV & RV) activation rate (AR)
during short-duration ventricular fibrillation (SDVF, <1 min) and long-duration
ventricular fibrillation VF (LDVF, >1 min) in normal and heart failure (HF)
canine hearts. METHODS: Ventricular fibrillation (VF) was electrically induced in
six healthy dogs (control group) and six dogs with right ventricular pacing
induced congestive HF (HF group). Two 64-electrode basket catheters deployed in
the LV and RV were used for global endocardium electrical mapping. The AR of VF
was estimated by fast Fourier transform analysis from each electrode. RESULTS: In
the control group, the LV was activated faster than the RV in the first 20 s,
after which there was no detectable difference in the AR between them. When
analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF,
the posterior LV was activated fastest, while the anterior was slowest. In the HF
group, a detectable AR gradient existed between the two ventricles within 3 min
of VF, with the LV activating more quickly than the RV. When analyzing the
distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of
the LV was activated fastest, while the anterior was activated slowest.
CONCLUSIONS: A global bi-ventricular endocardial AR gradient existed within the
first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR
gradient was always observed in both SDVF and LDVF in HF hearts. The findings of
this study suggest that LDVF in HF hearts can be maintained differently from
normal hearts, which accordingly should lead to the development of different
management strategies for LDVF resuscitation.
PMID- 28407745
TI - The expression of fibronectin is significantly suppressed in macrophages to exert
a protective effect against Staphylococcus aureus infection.
AB - BACKGROUND: Fibronectin (Fn) plays a major role in the attachment of
Staphylococcus aureus to host cells by bridging staphylococcal fibronectin
binding proteins (FnBPs) and cell-surface integrins. A previous study
demonstrated that the phagocytosis of S. aureus by macrophages is enhanced in the
presence of exogenous Fn. We recently found that FnBPs overexpression also
enhances phagocytic activity. The effect of S. aureus infection on the expression
of macrophage Fn was investigated. RESULT: The level of Fn secreted by monocytes
(THP-1), macrophages, human lung adenocarcinoma (A549) cells, and hepatocellular
carcinoma (HepG2) cells in response to S. aureus infection was determined by
Western blotting and it was significantly suppressed only in macrophages. The
activation of signaling pathways associated with Fn regulation in macrophages and
HepG2 cells was also investigated by Western blotting. Erk was activated in both
macrophages and HepG2 cells, whereas Src-JNK-c-Jun signaling was only activated
in macrophages. A significant decrease in macrophage viability was observed in
response to S. aureus infection in the presence of exogenous Fn. CONCLUSION: The
Src-JNK-c-Jun signaling pathway was activated in macrophages in response to S.
aureus infection and resulted in the suppression of Fn expression. This
suppression may play a protective role in macrophages against S. aureus
infection. This study provides the first demonstration that Fn is suppressed in
macrophages by S. aureus infection.
PMID- 28407746
TI - Understanding experiences of and preferences for service user and carer
involvement in physical health care discussions within mental health care
planning.
AB - BACKGROUND: People with severe mental illness suffer more physical comorbidity
than the general population, which can require a tailored approach to physical
health care discussions within mental health care planning. Although evidence
pertaining to service user and carer involvement in mental health care planning
is accumulating, current understanding of how physical health is prioritised
within this framework is limited. Understanding stakeholder experiences of
physical health discussions within mental health care planning, and the key
domains that underpin this phenomena is essential to improve quality of care. Our
study aimed to explore service user, carer and professional experiences of and
preferences for service user and carer involvement in physical health discussions
within mental health care planning, and develop a conceptual framework of
effective user-led involvement in this aspect of service provision. METHODS: Six
focus groups and four telephone interviews were carried out with twelve service
users, nine carers, three service users with a dual service user and carer role,
and ten mental health professionals recruited from one mental health Trust in the
United Kingdom. Data was analysed utilising a thematic approach, analysed
separately for each stakeholder group, and combined to aid comparisons. RESULTS:
No service users or carers recalled being explicitly involved in physical health
discussions within mental health care planning. Six prerequisites for effective
service user and carer involvement in physical care planning were identified.
Three themes confirmed general mental health care planning requirements:
tailoring a collaborative working relationship, maintaining a trusting
relationship with a professional, and having access to and being able to edit a
living document. Three themes were novel to feeling involved in physical health
care planning discussions: valuing physical health equally with mental health;
experiencing coordination of care between physical-mental health professionals,
and having a physical health discussion that is personalised. CONCLUSIONS: High
quality physical health care discussions within the care planning process demands
action at multiple levels. A conceptual framework is presented which provides an
evidence-based foundation for service level improvement. Further work is
necessary to develop a new patient reported outcome measure to enable meaningful
quantification of health care quality and patient experience.
PMID- 28407747
TI - Antipsychotic prescribing for vulnerable populations: a clinical audit at an
acute Australian mental health unit at two-time points.
AB - BACKGROUND: Antipsychotics are recognised as a critical intervention for
schizophrenia and bipolar disorder. Guidelines globally endorse the routine
practice of antipsychotic monotherapy, at the minimum effective dose. Even in
treatment-resistant schizophrenia, clozapine use is endorsed before combining
antipsychotics. This aim of this study was to review antipsychotic polytherapy
alone, high-dose therapy alone, polytherapy and high-dose prescribing patterns in
adults discharged from an inpatient mental health unit at two time-points, and
the alignment of this prescribing with clinical guideline recommendations.
Additionally, associations with polytherapy and high-dose antipsychotic
prescribing, including patient and clinical characteristics, were explored.
METHODS: A retrospective clinical audit of 400 adults (200 patients at two
different time-points) discharged with at least one antipsychotic. Preliminary
findings and education sessions were provided to physicians between Cohorts.
Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose
therapy) were compared between study Cohorts using chi-squared and rank-sum
tests. Associations between outcomes and covariates were assessed using
multivariable logistic regression. RESULTS: Most patients (62.5%) were discharged
on a single antipsychotic within the recommended dose range. There was a clear
preference for prescribing second generation antipsychotics, and in this respect,
prescribing is aligned with current evidence-based guidelines. However, sub
optimal prescribing practices were identified for both Cohorts in relation to
polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent
hospitalisations and previous clozapine use significantly increased the risk of
all three prescribing outcomes at discharge. CONCLUSIONS: In a significant
minority, antipsychotic prescribing did not align with clinical guidelines
despite increased training, indicating that the education program alone was
ineffective at positively influencing antipsychotic prescribing practices.
Further consideration should be given when prescribing antipsychotics for
involuntary patients, people with frequent hospitalisations, and those who have
previously trialled clozapine.
PMID- 28407748
TI - The role of ethnicity in pathways to emergency psychiatric services for clients
with psychosis.
AB - BACKGROUND: This study investigates the role of ethnicity in pathways to
emergency mental health care in Toronto for clients with psychosis, while taking
into account neighborhood factors. Previous literature has focused on Afro
Caribbean clients, reporting an increased risk of accessing mental health care
through negative pathways. METHODS: A retrospective chart review for clients from
6 different ethnic origin groups presenting with psychosis - East Asian, South
Asian, Black African, Black Caribbean, White European, and White North American -
was undertaken in a psychiatric emergency department (ED). Logistic regression
models were constructed to examine the relationship between pathways to care
(involuntary detention under the Mental Health Act (MHA), police or ambulance
referral, accompaniment by family or friends) with individual and neighbourhood
factors. RESULTS: A total of 765 clients were included in the study. East Asian
(OR =2.36, p < 0.01) and South Asian (OR 2.99, p < 0.01) origin clients have
increased odds of presenting to the ED while involuntarily detained under the
MHA. Involuntary status under the MHA increased the odds of presenting via police
or ambulance (OR 8.27, p < 0.001). East Asian origin clients have increased odds
of presenting to the ED by police or ambulance (OR =2.10, p < 0.05). Clients from
neighbourhoods with higher levels of residential instability have increased odds
of presenting by police or ambulance (OR =1.35, p < 0.01), while clients from
neighbourhoods with higher levels of ethnic concentration have increased odds of
being accompanied to the ED by family or friends (OR =1.33, p < 0.01).
CONCLUSION: In contrast to previous studies, East Asian and South Asian origin
clients with psychosis have increased odds of a coercive pathway to emergency
psychiatric services in Toronto. Black African and Black Caribbean origin clients
do not have increased odds of a coercive pathway. Clients living in areas with
high levels of residential instability are more likely to encounter a negative
pathway. Ethnic concentration may be a supportive factor in family and friend
accompaniment.
PMID- 28407749
TI - Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes
disease progression in human gastric cancer.
AB - BACKGROUND: OPCML belongs to the IgLON family of Ig domain-containing GPI
anchored cell adhesion molecules and was recently found to be involved in
carcinogenesis, while its role in gastric cancer remains unclear. METHODS: We
assessed expression and biological behavior of OPCML in gastric cancer. RESULTS:
OPCML expression was markedly reduced in tumor tissues and cancer cell lines.
Decreased OPCML expression had a significant association with unfavorable tumor
stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that
OPCML was an independent prognostic factor for overall survival in gastric cancer
(p = 0.002). In addition, ectopic expression of OPCML in cancer cells
significantly inhibited cell viability (p < 0.01) and colony formation (p <
0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed
tumor formation in nude mice. The alterations of phosphorylation status of AKT
and its substrate GSK3beta, up-regulation of pro-apoptotic regulators including
caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27,
were implicated in the biological activity of OPCML in cancer cells. CONCLUSION:
Down-regulated OPCML expression might serve as an independent predictor for
unfavorable prognosis of patients, and the biological behavior supports its role
as a tumor suppressor in gastric cancer.
PMID- 28407750
TI - Adjuvant treatment recommendations for patients with ER-positive/HER2-negative
early breast cancer by Swiss tumor boards using the 21-gene recurrence score
(SAKK 26/10).
AB - BACKGROUND: To evaluate the effect of Recurrence Score(r) results (RS; Oncotype
DX(r) multigene assay ODX) on treatment recommendations by Swiss
multidisciplinary tumor boards (TB). METHODS: SAKK 26/10 is a multicenter,
prospective cohort study of early breast cancer patients: Eligibility: R0
resection, >=10% ER+ malignant cells, HER2-, pN0/pN1a. Patients were stratified
into low-risk (LR) and non-low-risk (NLR) groups based on involved nodes (0 vs 1
3) and five additional predefined risk factors. Recommendations were classified
as hormonal therapy (HT) or chemotherapy plus HT (CT + HT). Investigators were
blinded to the statistical analysis plan. A 5%/10% rate of recommendation change
in LR/NLR groups, respectively, was assumed independently of RS (null
hypotheses). RESULTS: Two hundred twenty two evaluable patients from 18 centers
had TB recommendations before and after consideration of the RS result. A
recommendation change occurred in 45 patients (23/154 (15%, 95% CI 10-22%) in the
LR group and 22/68 (32%, 95% CI 22-45%) in the NLR group). In both groups the
null hypothesis could be rejected (both p < 0.001). Specifically, in the LR
group, only 5/113 (4%, 95% CI 1-10%) with HT had a recommendation change to CT +
HT after consideration of the RS, while 18/41 (44%, 95% CI 28-60%) of patients
initially recommended CT + HT were subsequently recommended only HT. In the NLR
group, 3/19 (16%, 95% CI 3-40%) patients were changed from HT to CT + HT, while
19/48 (40%, 95% CI 26-55%) were changed from CT + HT to HT. CONCLUSION: There was
a significant impact of using the RS in the LR and the NLR group but only 4% of
LR patients initially considered for HT had a recommendation change (RC);
therefore these patients could forgo ODX testing. A RC was more likely for NLR
patients considered for HT. Patients considered for HT + CT have the highest
likelihood of a RC based on RS.
PMID- 28407751
TI - Transcriptome analysis reveals potential mechanisms underlying differential heart
development in fast- and slow-growing broilers under heat stress.
AB - BACKGROUND: Modern fast-growing broilers are susceptible to heart failure under
heat stress because their relatively small hearts cannot meet increased need of
blood pumping. To improve the cardiac tolerance to heat stress in modern broilers
through breeding, we need to find the important genes and pathways that
contribute to imbalanced cardiac development and frequent occurrence of heat
related heart dysfunction. Two broiler lines - Ross 708 and Illinois - were
included in this study as a fast-growing model and a slow-growing model
respectively. Each broiler line was separated to two groups at 21 days posthatch.
One group was subjected to heat stress treatment in the range of 35-37 degrees C
for 8 h per day, and the other was kept in thermoneutral condition. Body and
heart weights were measured at 42 days posthatch, and gene expression in left
ventricles were compared between treatments and broiler lines through RNA-seq
analysis. RESULTS: Body weight and normalized heart weight were significantly
reduced by heat stress only in Ross broilers. RNA-seq results of 44 genes were
validated using Biomark assay. A total of 325 differentially expressed (DE) genes
were detected between heat stress and thermoneutral in Ross 708 birds, but only 3
in Illinois broilers. Ingenuity pathway analysis (IPA) predicted dramatic changes
in multiple cellular activities especially downregulation of cell cycle.
Comparison between two lines showed that cell cycle activity is higher in Ross
than Illinois in thermoneutral condition but is decreased under heat stress.
Among the significant pathways (P < 0.01) listed for different comparisons,
"Mitotic Roles of Polo-like Kinases" is always ranked first. CONCLUSIONS: The
increased susceptibility of modern broilers to cardiac dysfunction under heat
stress compared to slow-growing broilers could be due to diminished heart
capacity related to reduction in relative heart size. The smaller relative heart
size in Ross heat stress group than in Ross thermoneutral group is suggested by
the transcriptome analysis to be caused by decreased cell cycle activity and
increased apoptosis. The DE genes in RNA-seq analysis and significant pathways in
IPA provides potential targets for breeding of heat-tolerant broilers with
optimized heart function.
PMID- 28407752
TI - Detection of high serum levels of beta-D-Glucan in disseminated nocardial
infection: a case report.
AB - BACKGROUND: beta-D-glucan (BDG) is a helpful diagnostic marker for many invasive
fungal infections, but not for nocardiosis. Here, we reported the first case of
nocardial infection with high serum level of BDG. CASE PRESENTATION: A 73-year
old man was hospitalized because of fever, headache, and appetite loss after 10
months of steroid and immunosuppressive therapy for cryptogenic organizing
pneumonia. With a diagnosis of bacterial pneumonia, treatment with
ampicillin/sulbactam was initiated. There was improvement on chest radiograph,
but fever persisted. Further work-up revealed multiple brain abscesses on cranial
magnetic resonance imaging (MRI). Serum galactomannan and BDG were elevated at
0.6 index and 94.7 pg/ml, respectively. Voriconazole was initiated for presumed
aspergillus brain abscess. However, fever persisted and consciousness level
deteriorated. Drainage of brain abscess was performed; based on the Gram stain
and Kinyoun acid-fast stain, disseminated nocardiosis was diagnosed. Voriconazole
was then shifter to trimethoprim/sulfamethoxazole. The presence of Nocardia
farcinica was confirmed by the 16S rRNA gene sequence. Treatment course was
continued; BDG level normalized after 1 month and cranial MRI showed almost
complete improvement after 2 months. CONCLUSION: BDG assay is widely used to
diagnose invasive fungal infection; therefore, clinicians should be aware that
Nocardia species may show cross-reactivity with BDG assay on serum.
PMID- 28407753
TI - Genomic characterization of two novel pathogenic avipoxviruses isolated from
pacific shearwaters (Ardenna spp.).
AB - BACKGROUND: Over the past 20 years, many marine seabird populations have been
gradually declining and the factors driving this ongoing deterioration are not
always well understood. Avipoxvirus infections have been found in a wide range of
bird species worldwide, however, very little is known about the disease ecology
of avian poxviruses in seabirds. Here we present two novel avipoxviruses from
pacific shearwaters (Ardenna spp), one from a Flesh-footed Shearwater (A.
carneipes) (SWPV-1) and the other from a Wedge-tailed Shearwater (A. pacificus)
(SWPV-2). RESULTS: Epidermal pox lesions, liver, and blood samples were examined
from A. carneipes and A. pacificus of breeding colonies in eastern Australia.
After histopathological confirmation of the disease, PCR screening was conducted
for avipoxvirus, circovirus, reticuloendotheliosis virus, and fungal agents. Two
samples that were PCR positive for poxvirus were further assessed by next
generation sequencing, which yielded complete Shearwaterpox virus (SWPV) genomes
from A. pacificus and A. carneipes, both showing the highest degree of similarity
with Canarypox virus (98% and 67%, respectively). The novel SWPV-1 complete
genome from A. carneipes is missing 43 genes compared to CNPV and contains 4
predicted genes which are not found in any other poxvirus, whilst, SWPV-2
complete genome was deemed to be missing 18 genes compared to CNPV and a further
15 genes significantly fragmented as to probably cause them to be non-functional.
CONCLUSION: These are the first avipoxvirus complete genome sequences that infect
marine seabirds. In the comparison of SWPV-1 and -2 to existing avipoxvirus
sequences, our results indicate that the SWPV complete genome from A. carneipes
(SWPV-1) described here is not closely related to any other avipoxvirus genome
isolated from avian or other natural host species, and that it likely should be
considered a separate species.
PMID- 28407754
TI - Effect of audit and feedback with peer review on general practitioners'
prescribing and test ordering performance: a cluster-randomized controlled trial.
AB - BACKGROUND: Much research worldwide is focussed on cost containment and better
adherence to guidelines in healthcare. The research focussing on professional
behaviour is often performed in a well-controlled research setting. In this study
a large-scale implementation of a peer review strategy was tested on both test
ordering and prescribing behaviour in primary care in the normal quality
improvement setting. METHODS: We planned a cluster-RCT in existing local quality
improvement collaboratives (LQICs) in primary care. The study ran from January
2008 to January 2011. LQICs were randomly assigned to one of two trial arms, with
each arm receiving the same intervention of audit and feedback combined with peer
review. Both arms were offered five different clinical topics and acted as blind
controls for the other arm. The differences in test ordering rates and
prescribing rates between both arms were analysed in an intention-to-treat pre
post analysis and a per-protocol analysis. RESULTS: Twenty-one LQIC groups,
including 197 GPs working in 88 practices, entered the trial. The intention-to
treat analysis did not show a difference in the changes in test ordering or
prescribing performance between intervention and control groups. The per-protocol
analysis showed positive results for half of the clinical topics. The increase in
total tests ordered was 3% in the intervention arm and 15% in the control arm.
For prescribing the increase in prescriptions was 20% in the intervention arm and
66% in the control group. It was observed that the groups with the highest
baseline test ordering and prescription volumes showed the largest improvements.
CONCLUSIONS: Our study shows that the results from earlier work could not be
confirmed by our attempt to implement the strategy in the field. We did not see a
decrease in the volumes of tests ordered or of the drugs prescribed but were able
to show a lesser increase instead. Implementing the peer review with audit and
feedback proved to be not feasible in primary care in the Netherlands. TRIAL
REGISTRATION: This trial was registered at the Dutch trial register under number
ISRCTN40008171 on August 7th 2007.
PMID- 28407755
TI - Inflammatory Bowel Disease (IBD) pharmacotherapy and the risk of serious
infection: a systematic review and network meta-analysis.
AB - BACKGROUND: The magnitude of risk of serious infections due to available medical
therapies of inflammatory bowel disease (IBD) remains controversial. We conducted
a systematic review and network meta-analysis of the existing IBD literature to
estimate the risk of serious infection in adult IBD patients associated with
available medical therapies. METHODS: Studies were identified by a literature
search of PubMed, Cochrane Library, Medline, Web of Science, Scopus, EMBASE, and
ProQuest Dissertations and Theses. Randomized controlled trials comparing IBD
medical therapies with no restrictions on language, country of origin, or
publication date were included. A network meta-analysis was used to pool direct
between treatment comparisons with indirect trial evidence while preserving
randomization. RESULTS: Thirty-nine articles fulfilled the inclusion criteria;
one study was excluded from the analysis due to disconnectedness. We found no
evidence of increased odds of serious infection in comparisons of the different
treatment strategies against each other, including combination therapy with a
biologic and immunomodulator compared to biologic monotherapy. Similar results
were seen in the comparisons between the newer biologics (e.g. vedolizumab) and
the anti-tumor necrosis factor agents. CONCLUSIONS: No treatment strategy was
found to confer a higher risk of serious infection than another, although wide
confidence intervals indicate that a clinically significant difference cannot be
excluded. These findings provide a better understanding of the risk of serious
infection from IBD pharmacotherapy in the adult population. PROSPERO
REGISTRATION: The protocol for this systematic review was registered on PROSPERO
( CRD42014013497 ).
PMID- 28407756
TI - Alpha-fetoprotein elevation in NUT midline carcinoma: a case report.
AB - BACKGROUND: Nuclear protein in testis (NUT) midline carcinoma is a rarely
diagnosed and potentially under-recognized type of squamous carcinoma that is
considered one of the most aggressive human solid tumors. Alpha-fetoprotein
elevation has been associated with chronic liver diseases and a limited number of
cancers. In particular, in presence of a mediastinal mass in a young man, alpha
fetoprotein elevation is considered nearly pathognomonic of a non-seminoma germ
cell tumor. CASE PRESENTATION: A 22-year old man without any comorbidity was
diagnosed with a large mediastinal mass with skeletal and lymph node metastases.
The clinical picture was dominated by a life-threatening superior vena cava
syndrome with elevated alpha-fetoprotein and lactate dehydrogenase that supported
the diagnostic suspicion of mediastinal germ-cell tumor. However, a biopsy showed
a poorly-differentiated and diffusely necrotic carcinoma. We eventually reached
the diagnosis of the peculiar entity of NUT midline carcinoma, but the
differential diagnosis was quite challenging also because alpha-fetoprotein is
not reported as a marker of NUT midline carcinoma. Notably, alpha-fetoprotein
levels correlated with disease course. CONCLUSIONS: The life-threatening
aggressiveness of NUT midline carcinoma mandates to reach the right diagnosis in
the shortest possible time. In this regard, poorly differentiated carcinomas
lacking glandular differentiation mandate testing for NUT expression by
immunohistochemistry. Awareness of a potentially misleading tumor marker
elevation can help to broaden the differential diagnosis and establish the most
appropriate treatment.
PMID- 28407757
TI - Erratum to: Does continuous trusted adult support in childhood impart life-course
resilience against adverse childhood experiences - a retrospective study on adult
health-harming behaviours and mental well-being.
PMID- 28407758
TI - School grade and sex differences in domain-specific sedentary behaviors among
Japanese elementary school children: a cross-sectional study.
AB - BACKGROUND: It is vital to reduce the proportion of sedentary behavior in
children. Understanding the duration and behavioral context is needed. The
present study examined school-grade and sex differences in domain-specific
sedentary times and concurrence with screen-time guidelines among Japanese
elementary school children. METHODS: A total of 625 children (330 boys) were
surveyed in 2010 and 2014. Using a questionnaire, data regarding participants'
grade (first through third grades: lower grades; fourth through six grades:
higher grades), sex, weight, and height were collected in addition to the time
spent per day engaging in each specific sedentary behavior separately: (1)
reading or listening to music, (2) TV or video viewing, (3) TV game use, (4)
internet use excluding class, (5) homework, and (6) car travel. Two-way analysis
of covariance and logistic regression analyses, adjusted for BMI and moderate to
vigorous physical activity, were used to examine school-grade and sex differences
in sedentary behaviors and the independent risk of exceeding recommended total
daily screen time (< 2 h). RESULTS: On 625 children, mean minutes (SD) of
sedentary behavior per week in (1) - (6) were 90.3 (123.4), 535.0 (356.6), 167.3
(222.1), 23.9 (70.9), 264.9 (185.3), and 33.4 (61.2) in weekdays and 42.1 (70.0),
323.9 (232.0), 123.0 (96.4), 15.8 (49.9), 74.4 (96.4), and 71.3 (84.9) in
weekends, respectively. There were differences in the minutes of sedentary
behavior between participants of 2010 and 2014; e.g., TV game use and homework in
weekdays and weekdays and car travel in weekends. Boys spent more time in TV game
use, and girls spent more time reading, listening to music, doing homework, and
car travel. Higher-grade students spent more time reading or listening to music,
using a computer, and doing homework. Higher-grade students were 2.09 times (95%
CI: 1.32 - 3.30) in whole week, 2.08 times (95% CI: 1.45 - 3.00) in weekday, and
1.88 times (95% CI: 1.29 - 2.74) in weekend more likely to spend >=2 h per day in
domains (2) - (4) (screen-time) than lower-grade students. CONCLUSIONS: Time
spent engaging in each domain-specific sedentary behavior differed according to
sex and school grade. Higher-grade students were less likely to meet screen-time
guidelines. These findings highlight the need for domain-focused strategies to
decrease sedentary behavior in Japanese school-age children.
PMID- 28407759
TI - A new clinical algorithm scoring for management of suspected foreign body
aspiration in children.
AB - BACKGROUND: Foreign Body Aspiration (FBA) is a serious problem in children and
delays in diagnosis and management can be devastating. The history is often
vague, with subtle physical and chest radiograph abnormalities. This study aims
to determine the indications for bronchoscopy in children with suspected FBA and
evaluate the key clinical and statistically significant predictors of FBA, based
on the patients' historical, physical and radiological findings at presentation.
METHODS: This is a retrospective observational study, including patients who were
admitted between January 2001 to January 2011 with suspected FBA. Their
presenting history, physical exam, radiological and bronchoscopic findings were
analyzed. RESULTS: Three hundred children with a mean age of 2.1 +/- 1.7 years
were included. In children with both abnormal physical and radiological findings,
47.2% had proven FBA. If either was abnormal, the likelihood reduced to 32-33.3%;
if both were normal, only 7.4% had a FB. Witnessed choking (adjusted OR 2.1, 95%
CI 1.03-4.3; P = 0.041), noisy breathing/stridor/dysphonia (adjusted OR 2.7, 95%
CI 1.2-6.2; P = 0.015), new onset/recurrent /persistent wheeze (adjusted OR 4.6,
95% CI 1.8-11.8; P = 0.002), abnormal radiological findings (adjusted OR 4.0, 95%
CI 1.9-8.5; P < 0.001), and unilateral reduced air entry (adjusted OR 2.9, 95% CI
1.5-5.5; P = 0.001) were significant predictors of FBA (P < 0.05). When three or
more risk factors were present, the cumulative proportion of children with proven
FBA increased significantly. The discriminative ability of the model was found to
be good; the area under the ROC curve value was 0.76 (95% CI 0.70, 0.82). The
predicted cutoff score derived using ROC analysis was found to co-relate well
with known clinically significant predictors of FBA. This supports our algorithm
and scoring system. CONCLUSIONS: A high index of suspicion is required in
diagnosing airway FB. Our proposed clinical algorithm and scoring system hopes to
empower physicians to accurately predict patients with a high likelihood of FBA.
PMID- 28407760
TI - A comparative study of bone biopsies from the iliac crest, the tibial bone, and
the lumbar spine.
AB - BACKGROUND: Patients with an impaired renal function show a high incidence of
bone and mineral disturbances. These 'chronic kidney disease - mineral and bone
disorders' (CKD-MBD) range from high turnover osteoporosis to adynamic bone
disease. Currently, the histomorphometric analysis of a bone biopsy taken from
the iliac crest is viewed as the gold standard for CKD-MBD subtype
differentiation. However, the clinical relevance of such a biopsy is questionable
since iliac crest fractures are an extremely rare finding. Therefore, we aimed to
elucidate if the histomorphometric parameter 'trabecular bone volume (BV/TV)'
from the iliac crest is representative for other biopsy locations. We chose two
skeletal sites of higher fracture risk for testing, namely, the tibial bone and
the lumbar spine, to examine if the current gold standard of bone biopsy is
indeed golden. METHODS: Bone biopsies were taken from 12 embalmed body donors at
the iliac crest, the proximal tibia, and the lumbar vertebral body, respectively.
Masson-Goldner stained sections of methyl methacrylate embedded biopsies were
used for trabecular bone volume calculation. Furthermore, exemplary MU-computed
tomography (XtremeCT) scans with subsequent analysis were performed. RESULTS:
Median values of trabecular bone volume were comparable between all body donors
with median (interquartile range, IQR) 18.3% (10.9-22.9%) at the iliac crest,
21.5% (9.5-40.1%) at the proximal tibia, and 16.3% (11.4-25.0%) at the lumbar
spine. However, single values showed extensive intra-individual variation, which
were also confirmed by XtremeCT imaging. CONCLUSIONS: Distinct intra-individual
heterogeneity of trabecular bone volume elucidate why a bone biopsy from one site
does not necessarily predict patient relevant endpoints like hip or spine
fractures. Physicians interpreting bone biopsy results should know this
limitation of the current gold standard for CKD-MBD diagnostic, especially, when
systemic therapeutic decisions should be based on it.
PMID- 28407761
TI - Acute-phase diagnosis of murine and scrub typhus in Belgian travelers by
polymerase chain reaction: a case report.
AB - BACKGROUND: Rickettsiosis is a potential life threatening infectious disease in
travelers. Clinical recognition is not always straightforward, as typical
manifestations such as rash and/or eschar may be absent. Definite diagnosis is
based on seroconversion and therefore often delayed until the convalescent phase
of disease. CASE PRESENTATION: In this case report, we describe four patients
with severe travel-related rickettsiosis (two patients with murine- and two
patients with scrub typhus), in whom acute- phase diagnosis was possible by real
time polymerase chain reaction on serum or blood. CONCLUSIONS: Despite its
limitations, we think that polymerase chain reaction can contribute significantly
to the early diagnosis and treatment of rickettsial disease in travelers.
PMID- 28407762
TI - Erratum to: Antibiotic resistance and biofilm production among the strains of
Staphylococcus aureus isolated in a tertiary care hospital in Nepal.
PMID- 28407764
TI - Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on
dialysis -case report.
AB - BACKGROUND: Although the prescribing information for Venlafaxine extended release
includes a discussion about possible increases in total cholesterol and
triglycerides (TG) seen in healthier adult patients during premarketing clinical
trials, no post-marketing studies or case reports, that discuss the effects of
venlafaxine on TG in elderly patients with chronic kidney disease. CASE
PRESENTATION: We report a 71 year-old male patient with end-stage renal disease
on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia,
and hypertension. This patient twice demonstrated the severe rises in
triglycerides while taking the antidepressant, i.e., venlafaxine, and
discontinuing the long-term use of fenofirate. The adverse drug reaction sub
committee at the hospital rated the second event as a "probable reaction" using
the Naranjo nomogram, accordingly. CONCLUSIONS: This case demonstrates the risk
of changes in lipid profiles while taking venlafaxine and receiving on and off
fenofibrate therapy in the older adult patient with chronic kidney disease and
under hemodialysis. Regular monitoring for lipid changes after starting
venlafaxine is strongly advised for patients with existing risk factors.
PMID- 28407765
TI - Government supervision on quality of smoking-cessation counselling in midwifery
practices: a qualitative exploration.
AB - BACKGROUND: The Dutch Healthcare Inspectorate supervises care providers in order
to improve quality of care. Recently the inspectorate assessed and promoted the
use of a guideline on smoking-cessation counselling in midwifery practices. The
supervision programme consisted of an announcement of the enforcement deadline
for the guideline and site visits. The purpose of our qualitative study was to
identify factors related to guideline adherence after the supervision programme,
and investigate whether the programme had helped improve adherence. METHODS: We
conducted semi-structured interviews with inspected and non-inspected midwives.
Additionally, we studied documents and observed the inspection process. The
sampled midwives all work in primary care midwifery practices providing care to
pregnant smokers. The questions included the current provision of smoking
cessation counselling, support to the midwife in counselling, recent changes in
provision of counselling, reasons for recent changes, knowledge about the
supervision programme, and experiences with supervision by the inspectorate.
RESULTS: Our results show that guideline adherence depends on several factors.
Awareness and familiarity with the guideline are important, as is outcome
expectancy. Additionally, motivation, guideline factors and environment factors
were mentioned. Besides these previously documented factors, we found that
professional collaboration also determined guideline adherence. Increased
collaboration in counselling is associated with greater adherence to the
guideline, such as provision of counselling and taking required training. The
supervision programme helped improve stop-smoking counselling, by making midwives
aware of the counselling and giving them an extrinsic motivation to provide
counselling. CONCLUSION: Motivation and environmental aspects were the most
important factors related to guideline adherence, and professional environment
was added as significant factor. The improved guideline adherence is partly
attributable to the supervision programme.
PMID- 28407763
TI - Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative
stress via regulating LOX-1 and PI3K/Akt/eNOS pathways.
AB - BACKGROUND: Atherosclerosis is a common cardiovascular disease that causes
myocardial infarction, heart failure, and stroke. Increased oxidized low density
lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of
atherogenesis. Klotho, an anti-aging protein, has been reported to protect
against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim
of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL
treated human umbilical vein endothelial cells (HUVECs). METHODS: After pre
treatment with 200 pMKlotho for 1 h, HUVECs were stimulated with 50 MUg/ml ox-LDL
for 24 h. Reactive oxygen species (ROS) and superoxide dismutase (SOD) levels
were analyzed in the cells. Nitric oxide (NO) concertation was measured in the
medium supernatant. Related proteins or genes were detected with Western blot or
real time PCR, respectively, in the cell lysates. RESULTS: Initially, oxidative
damage in HUVECs was established by adding 50 MUg/mL ox-LDL, which resulted in
decreased cellular viability, SOD/Cu/Zn-SOD and endothelial NO synthase (eNOS)
expression and NO production, as well as increased malondialdehyde (MDA) levels,
ROS production, inducible NO synthase (iNOS), phosphatidyl inositol-3 kinase
(PI3K), protein kinase B (Akt), gp91 phox, and lectin-like ox-LDL receptor (LOX
1) expression in HUVECs. Pre-incubation with recombinant Klotho (200 pM)
significantly prevented all of these alterations. These results suggest that
Klotho can attenuate ox-LDL-induced oxidative stress in HUVECs through
upregulating oxidative scavengers (SOD and NO) viaactivating the PI3K/Akt/eNOS
pathway and depressing LOX-1expression. CONCLUSIONS: These results suggest that
Klotho has a potential therapeutic effect on attenuating endothelial dysfunction
and ameliorating atherosclerosis.
PMID- 28407766
TI - Novel lead structures with both Plasmodium falciparum gametocytocidal and asexual
blood stage activity identified from high throughput compound screening.
AB - BACKGROUND: Blocking malaria transmission is an important step in eradicating
malaria. In the field, transmission requires the production of sexual stage
Plasmodium parasites, called gametocytes, which are not effectively killed by the
commonly used anti-malarials allowing individuals to remain infectious after
clearance of asexual parasites. METHODS: To identify new gametocytocidal
compounds, a library of 45,056 compounds with diverse structures was screened
using a high throughput gametocyte viability assay. The characteristics of active
hits were further evaluated against asexual stage parasites in a growth
inhibition assay. Their cytotoxicity were tested against mammalian cells in a
cytotoxicity assay. The chemical scaffold similarity of active hits were studied
using scaffold cluster analysis. RESULTS: A set of 23 compounds were identified
and further confirmed for their activity against gametocytes. All the 23
confirmed compounds possess dual-activities against both gametocytes responsible
for human to mosquito transmission and asexual parasites that cause the clinical
symptoms. Three of these compounds were fourfold more active against gametocytes
than asexual parasites. Further cheminformatic analysis revealed three sets of
novel scaffolds, including highly selective 4-1H-pyrazol-5-yl piperidine analogs.
CONCLUSIONS: This study revealed important new structural scaffolds that can be
used as starting points for dual activity anti-malarial drug development.
PMID- 28407767
TI - E167K polymorphism of TM6SF2 gene affects cell cycle of hepatocellular carcinoma
cell HEPA 1-6.
AB - BACKGROUND: Some studties reported that the polymorphism of TM6SF2 gene E167K
affects the occurrence and the progression of hepatocytes carcinoma
(hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of
TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the
cell cycle in hepatocellular carcinoma cell HEPA1-6. METHODS: HEPA 1-6 cells
which could respectively overexpress TM6SF2 wild type and E167K variant were
cultured and HEPA 1-6 cells with zero load plasmids were used as matched control.
Flow cytometry was used to detect the cell cycles of these 3 type of HEPA 1-6
cells. Realtime fluores-cence quantitative PCR and western blot were used to
analyzed the expression of regulatory factors (Cyclin D1,p53,P16,P27,P21 and Rb)
of cell cycle. T-test was used in statistical analysis. RESULTS: Cell cycle phase
distribution was presented by the proportion of cells in each phases (%).
Compared with the control group, the cell cycle phase distribution (G1 phase
57.36 +/- 0.21%, G2/M phase 25.61 +/- 0.36%,S phases 19.31 +/- 0.25%) had no
differences in wild type group (G1 phase 57.63 +/- 0.28%, G2/M phase 25.77 +/-
0.51%, S phases 19.54 +/- 0.25%; P < 0.05). Between variant type group and wild
type group,G1 phase was significantly decreased (variant type group G1 phase
36.26 +/- 0.31%, P < 0.05),S phase and G2/M phase were increased(variant type
group S phase 28.41 +/- 0.31%, P < 0.05;G2/M phase 35.23 +/- 0.14%, P < 0.05),
respectively. Compared with control group,the relative expression of CyclinD1,P53
and Rb mRNA in variant type group was significantly upregulated (2.03 +/- 0.01 VS
1.04 +/- 0.06, 1.88 +/- 0.05 VS 1.37 +/- 0.03, 1.29 +/- 0.06 VS 1.15 +/- 0.03, P
< 0.05) and P27 mRNA in variant type group was significantly downregulated (0.56
+/- 0.02 VS 0.85 +/- 0.05, P < 0.05). Compared with wild type group, the relative
expression of CyclinD1,P53 and Rb mRNA in variant type group was significantly
upregulated (wild type group 1.00 +/- 0.00, 1.48 +/- 0.09, 1.18 +/- 0.01, P <
0.05) and P27 mRNA in variant type group was significantly downregulated (variant
type group 0.82 +/- 0.05,P < 0.05). There was no statistical significance between
wild type group and control group (P > 0.05). P16 and P21 expression showed no
statistical sigtfificance in any of these three groups (P > 0.05). CONCLUSION:
E167K polymorphism of TM6SF2 gene affects cell cycles of HEPA1-6 cells via up
regulating CyclinD1,P53 and Rb and down-regulating P27.
PMID- 28407768
TI - A study of noninvasive fractional flow reserve derived from a simplified method
based on coronary computed tomography angiography in suspected coronary artery
disease.
AB - BACKGROUND: The invasive fractional flow reserve has been considered the gold
standard for identifying ischaemia-related stenosis in patients with suspected
coronary artery disease. Determining non-invasive FFR based on coronary computed
tomographic angiography datasets using computational fluid dynamics tends to be a
demanding process. Therefore, the diagnostic performance of a simplified method
for the calculation of FFRCTA requires further evaluation. OBJECTIVES: The aim of
this study was to investigate the diagnostic performance of FFRCTA calculated
based on a simplified method by referring to the invasive FFR in patient-specific
coronary arteries and clinical decision-making. METHODS: Twenty-nine subjects
included in this study underwent CCTA before undergoing clinically indicated
invasive coronary angiography for suspected coronary artery disease. Pulsatile
flow simulation and a novel boundary condition were used to obtain FFRCTA based
on the CCTA datasets. The Pearson correlation, Bland-Altman plots and the
diagnostic performance of FFRCTA and CCTA stenosis were analyzed by comparison to
the invasive FFR reference standard. Ischaemia was defined as an FFR or FFRCTA
<=0.80, and anatomically obstructive CAD was defined as a CCTA stenosis >50%.
RESULTS: FFRCTA and invasive FFR were well correlated (r = 0.742, P = 0.001).
Slight systematic underestimation was found in FFRCTA (mean difference 0.03,
standard deviation 0.05, P = 0.001). The area under the receiver-operating
characteristic curve was 0.93 for FFRCTA and 0.75 for CCTA on a per-vessel basis.
Per-patient accuracy, sensitivity and specificity were 79.3, 93.7 and 61.5%,
respectively, for FFRCTA and 62.1, 87.5 and 30.7%, respectively, for CCTA. Per
vessel accuracy, sensitivity and specificity were 80.6, 94.1 and 68.4%,
respectively, for FFRCTA and 61.6, 88.2 and 36.8%, respectively, for CCTA.
CONCLUSIONS: FFRCTA derived from pulsatile simulation with a simplified novel
boundary condition was in good agreement with invasive FFR and showed better
diagnostic performance compared to CCTA, suggesting that the simplified method
has the potential to be an alternative and accurate way to assess the
haemodynamic characteristics for coronary stenosis.
PMID- 28407769
TI - Geographic variation within the military health system.
AB - BACKGROUND: This study seeks to quantify variation in healthcare utilization and
per capita costs using system-defined geographic regions based on enrollee
residence within the Military Health System (MHS). METHODS: Data for fiscal years
2007 - 2010 were obtained from the Military Health System under a data sharing
agreement with the Defense Health Agency (DHA). DHA manages all aspects of the
Department of Defense Military Health System, including TRICARE. Adjusted rates
were calculated for per capita costs and for two procedures with high interest to
the MHS- back surgery and Cesarean sections for TRICARE Prime and Plus enrollees.
Coefficients of variation (CoV) and interquartile ranges (IQR) were calculated
and analyzed using residence catchment area as the geographic unit. Catchment
areas anchored by a Military Treatment Facility (MTF) were compared to catchment
areas not anchored by a MTF. RESULTS: Variation, as measured by CoV, was 0.37 for
back surgery and 0.13 for C-sections in FY 2010- comparable to rates documented
in other healthcare systems. The 2010 CoV (and average cost) for per capita costs
was 0.26 ($3,479.51). Procedure rates were generally lower and CoVs higher in
regions anchored by a MTF compared with regions not anchored by a MTF, based on
both system-wide comparisons and comparisons of neighboring areas. CONCLUSIONS:
In spite of its centrally managed system and relatively healthy beneficiaries
with very robust health benefits, the MHS is not immune to unexplained variation
in utilization and cost of healthcare.
PMID- 28407770
TI - Erratum to: The effect of pomegranate fresh juice versus pomegranate seed powder
on metabolic indices, lipid profile, inflammatory biomarkers, and the
histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide
induced type 2 diabetic Sprague-Dawley rats.
PMID- 28407771
TI - Amyloid precursor protein, lipofuscin accumulation and expression of autophagy
markers in aged bovine brain.
AB - BACKGROUND: Autophagy is a highly regulated process involving the bulk
degradation of cytoplasmic macromolecules and organelles in mammalian cells via
the lysosomal system. Dysregulation of autophagy is implicated in the
pathogenesis of many neurodegenerative diseases and integrity of the
autophagosomal - lysosomal network appears to be critical in the progression of
aging. Our aim was to survey the expression of autophagy markers and Amyloid
precursor protein (APP) in aged bovine brains. For our study, we collected
samples from the brain of old (aged 11-20 years) and young (aged 1-5 years)
Podolic dairy cows. Formalin-fixed and paraffin embedded sections were stained
with routine and special staining techniques. Primary antibodies for APP and
autophagy markers such as Beclin-1 and LC3 were used to perform
immunofluorescence and Western blot analysis. RESULTS: Histologically, the most
consistent morphological finding was the age-related accumulation of
intraneuronal lipofuscin. Furthermore, in aged bovine brains, immunofluorescence
detected a strongly positive immunoreaction to APP and LC3. Beclin-1
immunoreaction was weak or absent. In young controls, the immunoreaction for
Beclin-1 and LC3 was mild while the immunoreaction for APP was absent. Western
blot analysis confirmed an increased APP expression and LC3-II/LC3-I ratio and a
decreased expression of Beclin-1 in aged cows. CONCLUSIONS: These data suggest
that, in aged bovine, autophagy is significantly impaired if compared to young
animals and they confirm that intraneuronal APP deposition increases with age.
PMID- 28407772
TI - The end of a dogma: the safety of doxycycline use in young children for malaria
treatment.
AB - Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has
spread from Southeast Asia to Africa. Furthermore, the recent emergence of
resistance to artemisinin-based combination therapy (ACT) in Southeast Asia
highlights the need to identify new anti-malarial drugs. Doxycycline is
recommended for malaria chemoprophylaxis for travel in endemic areas, or in
combination with the use of quinine for malaria treatment when ACT is unavailable
or when the treatment of severe malaria with artesunate fails. However,
doxycycline is not used in young children under 8 years of age due to its
contraindication due to the risk of yellow tooth discolouration and dental enamel
hypoplasia. Doxycycline was developed after tetracycline and was labelled with
the same side-effects as the earlier tetracyclines. However, recent studies
report little or no effects of doxycycline on tooth staining or dental enamel
hypoplasia in children under 8 years of age. In the United States, the Centers
for Disease Control and Prevention have recommended the use of doxycycline for
the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in
young children. It is time to rehabilitate doxycycline and to recommend it for
malaria treatment in children under 8 years of age.
PMID- 28407773
TI - Minimally invasive, patient specific, beat-by-beat estimation of left ventricular
time varying elastance.
AB - BACKGROUND: The aim of this paper was to establish a minimally invasive method
for deriving the left ventricular time varying elastance (TVE) curve beat-by
beat, the monitoring of which's inter-beat evolution could add significant new
data and insight to improve diagnosis and treatment. The method developed uses
the clinically available inputs of aortic pressure, heart rate and baseline end
systolic volume (via echocardiography) to determine the outputs of left
ventricular pressure, volume and dead space volume, and thus the TVE curve. This
approach avoids directly assuming the shape of the TVE curve, allowing more
effective capture of intra- and inter-patient variability. RESULTS: The resulting
TVE curve was experimentally validated against the TVE curve as derived from
experimentally measured left ventricular pressure and volume in animal models, a
data set encompassing 46,318 heartbeats across 5 Pietrain pigs. This simulated
TVE curve was able to effectively approximate the measured TVE curve, with an
overall median absolute error of 11.4% and overall median signed error of -2.5%.
CONCLUSIONS: The use of clinically available inputs means there is potential for
real-time implementation of the method at the patient bedside. Thus the method
could be used to provide additional, patient specific information on intra- and
inter-beat variation in heart function.
PMID- 28407776
TI - Trends of medical expenditures and quality of life in US adults with diabetes:
the medical expenditure panel survey, 2002-2011.
AB - BACKGROUND: Studies indicate a relationship between cost and quality of life
(QOL) in diabetes care, however, the interaction is complex and the relationship
is not well understood. The aim of this study was to 1) examine the relationship
of quartiles of QOL on cost amongst U.S. adults with diabetes, 2) investigate how
the relationship may change over time, and 3) examine the incremental effect of
QOL on cost while controlling for other relevant covariates. METHODS: Data from
2002-2011 Medical Expenditure Panel Survey (MEPS) was used to examine the
association between QOL and medical expenditures among adults with diabetes (aged
>=18 years) N = 20,442. Unadjusted means were computed to compare total
healthcare expenditure and the out-of-pocket expenses by QOL quartile categories.
QOL measures were Physical Component Summary (PCS) and Mental Component Summary
(MCS) derived from the Short-Form 12. A two-part model was then used to estimate
adjusted incremental total healthcare expenditure and out-of-pocket expenses
adjusting for relevant covariates. RESULTS: Differences between the highest and
lowest quartiles totaled $11,801 for total expenditures and $989 for out-of
pocket expenses. Over time, total expenditures remained stable, while out-of
pocket expenses decreased, particularly for the lowest quartile of physical
component of QOL. Similar trends were seen in the mental component, however,
differences between quartiles were smaller (average $5,727 in total expenses;
$287 in out-of-pocket). After adjusting for covariates, those in the highest
quartile of physical component of QOL spent $7,500 less, and those in the highest
quartile of mental component spent $3,000 less than those in the lowest
quartiles. CONCLUSIONS: A clear gradient between QOL and cost with increasing
physical and mental QOL associated with lower expenditures and out-of-pocket
expenses was found. Over a 10-year time period those with the highest physical
QOL had significantly less medical expenditures compared to those with the lowest
physical QOL. This study demonstrates the significant individual and societal
impact poor QOL has on patients with diabetes. Understanding how differences in a
subjective measure of health, such as QOL, has on healthcare expenditures helps
reveal the burden of disease not reflected by using only behavioral and
physiological measures.
PMID- 28407775
TI - Telomere shortening and accelerated aging in COPD: findings from the BODE cohort.
AB - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) may be associated with
accelerated aging. Telomere shortening is a biomarker of aging. Cross-sectional
studies describe shorter telomeres in COPD compared with matched controls. No
studies have described telomere length trajectory and its relationship with COPD
progression. We investigated telomere shortening over time and its relationship
to clinical and lung function parameters in a COPD cohort and smoker controls
without COPD. METHODS: At baseline leukocyte telomere length was measured by qPCR
in 121 smokers with COPD and 121 without COPD matched by age (T/S0). The
measurements were repeated in 70 of those patients with COPD and 73 non-COPD
smokers after 3 years of follow up (T/S3). RESULTS: At initial measurement,
telomeres were shorter in COPD patients when compared to smoker controls (T/S =
0.68 +/- 0.25 vs. 0.88 +/- 0.52, p = 0.003) independent from age and sex. During
the follow-up period, we observed an accelerated telomere shortening in
individuals with COPD in contrast to smoker controls (T/S0 = 0.66 +/- 0.21 vs.
T/S3 = 0.46 +/- 0.16, p < 0.001, for the patients with COPD and T/S0 = 0.83 +/-
0.56 vs. T/S3 = 0.74 +/- 0.52, p = 0.023 for controls; GLIM, p = 0.001). This
shortening was inversely related to the baseline telomere length (r = -0.49, p <
0.001). No significant relationship was found between the rate of change in
telomere length and change in lung function in the patients with COPD (p > 0.05).
CONCLUSIONS: Compared with smokers, patients with COPD have accelerated telomere
shortening and this rate of attrition depends on baseline telomere length.
Furthermore, the telomere length and its rate of shortening did not relate to
clinical and lung function parameters changes over 3 years of follow-up.
PMID- 28407774
TI - ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway.
AB - Cancer cells are frequently confronted with metabolic stress in tumor
microenvironments due to their rapid growth and limited nutrient supply.
Metabolic stress induces cell death through ROS-induced apoptosis. However,
cancer cells can adapt to it by altering the metabolic pathways. AMPK and AKT are
two primary effectors in response to metabolic stress: AMPK acts as an energy
sensing factor which rewires metabolism and maintains redox balance. AKT broadly
promotes energy production in the nutrient abundance milieu, but the role of AKT
under metabolic stress is in dispute. Recent studies show that AMPK and AKT
display antagonistic roles under metabolic stress. Metabolic stress-induced ROS
signaling lies in the hub between metabolic reprogramming and redox homeostasis.
Here, we highlight the cross-talk between AMPK and AKT and their regulation on
ROS production and elimination, which summarizes the mechanism of cancer cell
adaptability under ROS stress and suggests potential options for cancer
therapeutics.
PMID- 28407777
TI - Automatic migraine classification via feature selection committee and machine
learning techniques over imaging and questionnaire data.
AB - BACKGROUND: Feature selection methods are commonly used to identify subsets of
relevant features to facilitate the construction of models for classification,
yet little is known about how feature selection methods perform in diffusion
tensor images (DTIs). In this study, feature selection and machine learning
classification methods were tested for the purpose of automating diagnosis of
migraines using both DTIs and questionnaire answers related to emotion and
cognition - factors that influence of pain perceptions. METHODS: We select 52
adult subjects for the study divided into three groups: control group (15),
subjects with sporadic migraine (19) and subjects with chronic migraine and
medication overuse (18). These subjects underwent magnetic resonance with
diffusion tensor to see white matter pathway integrity of the regions of interest
involved in pain and emotion. The tests also gather data about pathology. The DTI
images and test results were then introduced into feature selection algorithms
(Gradient Tree Boosting, L1-based, Random Forest and Univariate) to reduce
features of the first dataset and classification algorithms (SVM (Support Vector
Machine), Boosting (Adaboost) and Naive Bayes) to perform a classification of
migraine group. Moreover we implement a committee method to improve the
classification accuracy based on feature selection algorithms. RESULTS: When
classifying the migraine group, the greatest improvements in accuracy were made
using the proposed committee-based feature selection method. Using this approach,
the accuracy of classification into three types improved from 67 to 93% when
using the Naive Bayes classifier, from 90 to 95% with the support vector machine
classifier, 93 to 94% in boosting. The features that were determined to be most
useful for classification included are related with the pain, analgesics and left
uncinate brain (connected with the pain and emotions). CONCLUSIONS: The proposed
feature selection committee method improved the performance of migraine diagnosis
classifiers compared to individual feature selection methods, producing a robust
system that achieved over 90% accuracy in all classifiers. The results suggest
that the proposed methods can be used to support specialists in the
classification of migraines in patients undergoing magnetic resonance imaging.
PMID- 28407778
TI - Coping strategies and quality of life in caregivers of dependent elderly
relatives.
AB - BACKGROUND: Despite the importance of coping in caregiving, there are few studies
on the relationship between coping and quality of life in caregivers of the frail
dependent elderly. Thus, this study aims to analyze the relationship between
coping strategies and quality of life dimensions in primary caregivers of
dependent elderly relatives. METHODS: A cross-sectional study was conducted from
86 caregivers. Predictive variables were coping strategies (problem-focused,
emotion-focused, socially-supported, and dysfunctional); dependent variables were
quality of life dimensions (psychological, physical, relational, and
environmental); and potential confounding variables were age, gender, perceived
health and burden of caregiver, and functional capacity of care receiver.
Correlation coefficients were calculated and multiple linear regression analysis
was performed. RESULTS: After controlling for potential confounders,
dysfunctional coping was related to worse quality of life in the psychological
dimension, while emotion-focused and socially-supported coping were related to
superior psychological and environmental dimensions of quality of life. The
physical and relational dimensions of quality of life were not related to coping
strategies. CONCLUSIONS: 1) it is important to consider coping strategies in the
assessment of primary caregivers of dependent elderly relatives; 2) the quality
of life of caregivers is related to their coping strategies, 3) their quality of
life can be worsened by avoidance-type coping, and 4) their quality of life can
be improved by active emotion-focused coping and socially-supported coping.
PMID- 28407780
TI - Determining the gaps between Cochrane reviews and trials of effectiveness of
interventions for acute respiratory infections: an audit.
AB - BACKGROUND: Cochrane primarily aims to systematically review trials of
effectiveness that are important to inform clinical decisions. Editorial groups
support authors to achieve high-quality reviews and prioritise review proposals
in their clinical domain that are submitted or elicited. Prioritising proposals
requires two approaches, identifying (1) clinical practises for which the
evidence of effectiveness is uncertain and (2) interventions in which there are
trials of effectiveness (especially randomised controlled trials (RCTs)) not
systematically reviewed. This study addresses this second approach for the
Cochrane Acute Respiratory Infections Group (CARIG) in order to identify RCTs of
acute respiratory infections that have not been systematically reviewed. METHODS:
We exported, on the 9th of September 2014, and then compared the group's trials
register of RCTs against a list of current Cochrane ARI (systematic) Reviews to
identify gaps in topics (the same intervention and health condition) where
completed trials have not been systematically reviewed. We assigned a principle
intervention and health condition to each of 157 Cochrane reviews (CRs) and 5393
RCTs. RESULTS: A majority of topics had been systematically reviewed; however, a
substantial number (2174 or 41%) of RCTs were not included in any review. The
topic that had been systematically reviewed the most was antibiotic vs placebo
for pneumonia with 11 CRs and 205 RCTs. The topic that was the subject of most
RCTs was vaccination for influenza with 525 RCTs and 6 CRs. Also, 6 CRs had no
RCTs ('empty reviews'). CONCLUSIONS: We identified many RCT topics that have not
been systematically reviewed. They need to be addressed in a separate process to
establish their priority to clinicians.
PMID- 28407779
TI - Histologic effects of mandibular protrusion splints in antigen-induced TMJ
arthritis in rabbits.
AB - BACKGROUND: Although it is common clinical practice to treat children with
Juvenile Idiopathic Arthritis (JIA) with functional appliances, the scientific
evidence for this is limited. The aim of this study was to study the histologic
effects of mandibular protrusion splints in temporomandibular joint (TMJ)
arthritis in rabbits. METHODS: Twenty-eight ten-week old New Zealand white
rabbits were randomly divided into four groups: AO (TMJ arthritis, no splint), AS
(TMJ arthritis, mandibular splint advancement), OS (no arthritis, mandibular
splint advancement) and OO (no arthritis, no splint). TMJ arthritis was induced
in the groups AO and AS; 1 week later mandibular protrusion splints were placed
on the upper incisors of the AS and OS animals. After 60 days the animals were
sacrificed and a semiquantitative histologic evaluation of each TMJ was carried
out to analyze the amount of inflammation and bone modeling. RESULTS: AO and AS
animals had a higher inflammation score (AO = 1.3; AS = 1.8) than the non
arthritis groups (OO = 0.6; OS = 0.4). Whereas in the untreated control (OO) the
amount of apposition and resorption was almost in balance (+1), OS animals
displayed significantly more apposition (+9) and AO animals significantly more
resorption (-3) than the untreated control. Arthritis animals with protrusion
appliances (AS), however, had remarkably more bone apposition (+3) than
resorption, indicating a similar bony reaction as in healthy animals, although
reduced in extent. CONCLUSIONS: Mandibular advancement in rabbits with TMJ
arthritis is possible without detrimental histologic reactions and appears to
partially compensate for the bone loss seen in rabbits with TMJ arthritis but
without protrusion splints.
PMID- 28407781
TI - Early identification of patients requiring massive transfusion, embolization, or
hemostatic surgery for traumatic hemorrhage: a systematic review protocol.
AB - BACKGROUND: Hemorrhage is a major cause of early mortality following a traumatic
injury. The progression and consequences of significant blood loss occur quickly
as death from hemorrhagic shock or exsanguination often occurs within the first
few hours. The mainstay of treatment therefore involves early identification of
patients at risk for hemorrhagic shock in order to provide blood products and
control of the bleeding source if necessary. The intended scope of this review is
to identify and assess combinations of predictors informing therapeutic decision
making for clinicians during the initial trauma assessment. The primary objective
of this systematic review is to identify and critically assess any existing
multivariable models predicting significant traumatic hemorrhage that requires
intervention, defined as a composite outcome comprising massive transfusion,
surgery for hemostasis, or angiography with embolization for the purpose of
external validation or updating in other study populations. If no suitable
existing multivariable models are identified, the secondary objective is to
identify candidate predictors to inform the development of a new prediction rule.
METHODS: We will search the EMBASE and MEDLINE databases for all randomized
controlled trials and prospective and retrospective cohort studies developing or
validating predictors of intervention for traumatic hemorrhage in adult patients
16 years of age or older. Eligible predictors must be available to the clinician
during the first hour of trauma resuscitation and may be clinical, lab-based, or
imaging-based. Outcomes of interest include the need for surgical intervention,
angiographic embolization, or massive transfusion within the first 24 h. Data
extraction will be performed independently by two reviewers. Items for extraction
will be based on the CHARMS checklist. We will evaluate any existing models for
relevance, quality, and the potential for external validation and updating in
other populations. Relevance will be described in terms of appropriateness of
outcomes and predictors. Quality criteria will include variable selection
strategies, adequacy of sample size, handling of missing data, validation
techniques, and measures of model performance. DISCUSSION: This systematic review
will describe the availability of multivariable prediction models and summarize
evidence regarding predictors that can be used to identify the need for
intervention in patients with traumatic hemorrhage. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42017054589.
PMID- 28407782
TI - Triatoma vitticeps subcomplex (Hemiptera, Reduviidae, Triatominae): a new
grouping of Chagas disease vectors from South America.
AB - BACKGROUND: Triatomines have been grouped into complexes and subcomplexes based
largely on morphological and geographical distribution. Although these groupings
are not formally recognised as taxonomic ranks, they are likely monophyletic.
However, recent studies have demonstrated that some subcomplexes from South
America did not form monophyletic groups, and reorganisations have been
suggested. One suggested reorganisation is to exclude Triatoma vitticeps, T.
melanocephala, and T. tibiamaculata from the T. brasiliensis subcomplex. However,
T. vitticeps and T. melanocephala exhibit several similar characteristics,
including morphologic, cytogenetic, and phylogenetic features, a factor which
supports the creation of a new subcomplex. Thus, this study aimed to describe the
T. vitticeps subcomplex. RESULTS: T. vitticeps and T. melanocephala are sister
species and share a phylogenetic relationship, several similar morphological
characteristics, the same composition of constitutive heterochromatin (Xs CG-rich
and Y AT-rich), the same karyotype (2n = 20A + X1X2X3Y), and the same meiotic
behaviour during spermatogenesis. Based on karyosystematics, for example, the T.
vitticeps subcomplex may differ from all of the other subcomplexes from South
America, as well as from the Rhodniini tribe and the genus Panstrongylus. We
argue that the case of agmatoploidy involving the X chromosome was responsible
for the karyotype divergence of this subcomplex in relation to the other South
America subcomplexes. CONCLUSIONS: Based on the phenotypic characteristics
(morphology) and genotypes (cytogenetics and molecular features), we propose the
creation of the monophyletic T. vitticeps subcomplex, which we believe is
distinct from all other subcomplexes from South America.
PMID- 28407783
TI - Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin
resistance in gastric cancer cells.
AB - BACKGROUND: Cisplatin-based chemotherapy is frequently used to treat advanced
gastric cancer (GC). However, the resistance often occurs with the mechanisms
being not well understood. Recently, emerging evidence indicates that tumor
associated macrophages (TAMs) play an important role in chemoresistance of
cancer. As the important mediators in intercellular communications, exosomes
secreted by host cells mediate the exchange of genetic materials and proteins to
be involved in tumor aggressiveness. The aim of the study was to investigate
whether exosomes derived from TAMs mediate cisplatin resistance in gastric
cancer. METHODS: M2 polarized macrophages were obtained from mouse bone marrow or
human PBMCs stimulated with IL-4 and IL-13. Exosomes isolated from M2 macrophages
culture medium were characterized, and miRNA expression profiles of M2 derived
exosomes (M2-exos) were analyzed using miRNA microarray. In vitro cell coculture
was further conducted to investigate M2-exos mediated crosstalk between TAMs and
tumor cells. Moreover, the in vivo experiments were performed using a
subcutaneous transplantation tumor model in athymic nude mice. RESULTS: In this
study, we showed that M2 polarized macrophages promoted cisplatin (DDP)
resistance in gastric cancer cells and exosomes derived from M2 macrophages (M2
exos) are involved in mediating the resistance to DDP. Using miRNA profiles
assay, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs
in exosomes and cell lysate isolated from M2 polarized macrophage. Functional
studies revealed that exosomal miR-21 can be directly transferred from
macrophages to the gastric cancer cells, where it suppresses cell apoptosis and
enhances activation of PI3K/AKT signaling pathway by down-regulation of PTEN.
CONCLUSIONS: Our findings suggest that exosomal transfer of tumor-associated
macrophages derived miR-21 confer DDP resistance in gastric cancer, and targeting
exosome communication may be a promising new therapeutic strategy for gastric
cancer patients.
PMID- 28407784
TI - Relationships between gut microbiota, plasma metabolites, and metabolic syndrome
traits in the METSIM cohort.
AB - BACKGROUND: The gut microbiome is a complex and metabolically active community
that directly influences host phenotypes. In this study, we profile gut
microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from
the Metabolic Syndrome In Men (METSIM) study. RESULTS: We investigate gut
microbiota relationships with a variety of factors that have an impact on the
development of metabolic and cardiovascular traits. We identify novel
associations between gut microbiota and fasting serum levels of a number of
metabolites, including fatty acids, amino acids, lipids, and glucose. In
particular, we detect associations with fasting plasma trimethylamine N-oxide
(TMAO) levels, a gut microbiota-dependent metabolite associated with coronary
artery disease and stroke. We further investigate the gut microbiota composition
and microbiota-metabolite relationships in subjects with different body mass
index and individuals with normal or altered oral glucose tolerance. Finally, we
perform microbiota co-occurrence network analysis, which shows that certain
metabolites strongly correlate with microbial community structure and that some
of these correlations are specific for the pre-diabetic state. CONCLUSIONS: Our
study identifies novel relationships between the composition of the gut
microbiota and circulating metabolites and provides a resource for future studies
to understand host-gut microbiota relationships.
PMID- 28407786
TI - Bioinformatics analysis to screen the key prognostic genes in ovarian cancer.
AB - BACKGROUND: Ovarian cancer (OC) is a gynecological oncology that has a poor
prognosis and high mortality. This study is conducted to identify the key genes
implicated in the prognosis of OC by bioinformatic analysis. METHODS: Gene
expression data (including 568 primary OC tissues, 17 recurrent OC tissues, and 8
adjacent normal tissues) and the relevant clinical information of OC patients
were downloaded from The Cancer Genome Atlas database. After data preprocessing,
cluster analysis was conducted using the ConsensusClusterPlus package in R. Using
the limma package in R, differential analysis was performed to identify feature
genes. Based on Kaplan-Meier (KM) survival analysis, prognostic seed genes were
selected from the feature genes. After key prognostic genes were further screened
by cluster analysis and KM survival analysis, they were performed functional
enrichment analysis and multivariate survival analysis. Using the survival
package in R, cox regression analysis was conducted for the microarray data of
GSE17260 to validate the key prognostic genes. RESULTS: A total of 3668 feature
genes were obtained, among which 75 genes were identified as prognostic seed
genes. Then, 25 key prognostic genes were screened, including AXL, FOS, KLF6,
WDR77, DUSP1, GADD45B, and SLIT3. Especially, AXL and SLIT3 were enriched in
ovulation cycle. Multivariate survival analysis showed that the key prognostic
genes could effectively differentiate the samples and were significantly
associated with prognosis. Additionally, GSE17260 confirmed that the key
prognostic genes were associated with the prognosis of OC. CONCLUSION: AXL, FOS,
KLF6, WDR77, DUSP1, GADD45B, and SLIT3 might affect the prognosis of OC.
PMID- 28407785
TI - First autochthonous cases of canine thelaziosis in Slovakia: a new affected area
in Central Europe.
AB - BACKGROUND: The spirurid nematode Thelazia callipaeda, also called the "Oriental
eyeworm", is the causative agent of canine and human ocular thelaziosis. In the
past few years it has started to spread across central Europe and new endemic
areas have been established. The present study reports on the first four
autochthonous cases of canine ocular thelaziosis in the territory of Slovakia,
Central Europe. RESULTS: All cases were recorded in dogs living in eastern
Slovakia, near the border with the Ukraine. All worms collected were investigated
morphologically and their identification further confirmed at the molecular level
by PCR amplification and direct sequencing. Nucleotide sequences of partial T.
callipaeda cox1 and 28S rDNA gene fragments isolated from Slovak dogs were
submitted to the GenBank database under accession numbers KY476400 and KY476401,
respectively. CONCLUSIONS: Considering that all four cases were diagnosed in
animals that had never travelled abroad, there is clear evidence of an
autochthonous occurrence and thereby the further spread of T. callipaeda across
Europe. Moreover, at latitude of 48 degrees N, these cases might be considered as
the northernmost recorded cases of autochthonous in western and Central Europe.
PMID- 28407787
TI - Glucose-regulated protein 78 demonstrates antiviral effects but is more suitable
for hepatocellular carcinoma prevention in hepatitis B.
AB - BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and
hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV
or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78
(GRP78) can inhibit HBV replication, but promote virion secretion and
hepatocellular cancer cell invasion. For these reasons, the overall effect of
GRP78 on HBV production and whether to utilize the HBV replication-inhibitory
effect of GRP78 up-regulation or the hepatocellular cancer cell invasion
inhibitory effect of its down-regulation were further investigated in order to
improve the efficacy of current antiviral therapy. METHODS: GRP78 regulations in
HepG2.2.15 cells were conducted by transfections of expressing vector and small
interfering RNA, respectively. The changes in HBV replication, hepatitis B e
antigen (HBeAg) synthesis and hepatoma cell motility were monitored. RESULTS:
GRP78 overall decreased HBV production due to its HBV replication-inhibitory
effect time-dependently overwhelming virion secretion-promoting effect in
HepG2.2.15 cells. Unlike the parental cells (HepG2), HepG2.2.15 cells
demonstrated decreased expressions of the major genes in the interferon-beta1
dependent pathway. Moreover, the expressions of these genes were not affected by
GRP78 regulations. However, GRP78 was found to inhibit HBeAg secretion and to
increase the retro-transportation of capsid assembly-interfering HBeAg precursor
from the endoplasmic reticulum into the cytosol where new viral nucleocapsids
formed. Furthermore, GRP78 overexpression promoted wound healing process (the
motility) of HepG2.2.15 cells. In contrast, GRP78 knockdown enhanced HBV
replication and HBeAg secretion, but they were abolished by entecavir and furin
inhibitor, respectively. CONCLUSIONS: GRP78 mainly demonstrates anti-HBV effects,
reducing HBV production and HBeAg secretion. With due regard to the
hepatocellular cancer invasion risk of the overexpression and the rectifiability
of the unpleasant effects of the knockdown, GRP78 down-regulation may be more
suitable to serve as an additive strategy to cover the hepatocellular cancer
prevention shortage of current antiviral therapy in the future.
PMID- 28407788
TI - Absence of neurological abnormalities in mice homozygous for the Polr3a G672E
hypomyelinating leukodystrophy mutation.
AB - Recessive mutations in the ubiquitously expressed POLR3A gene cause one of the
most frequent forms of childhood-onset hypomyelinating leukodystrophy (HLD):
POLR3-HLD. POLR3A encodes the largest subunit of RNA Polymerase III (Pol III),
which is responsible for the transcription of transfer RNAs (tRNAs) and a large
array of other small non-coding RNAs. In order to study the central nervous
system pathophysiology of the disease, we introduced the French Canadian founder
Polr3a mutation c.2015G > A (p.G672E) in mice, generating homozygous knock-in
(KI/KI) as well as compound heterozygous mice for one Polr3a KI and one null
allele (KI/KO). Both KI/KI and KI/KO mice are viable and are able to reproduce.
To establish if they manifest a motor phenotype, WT, KI/KI and KI/KO mice were
submitted to a battery of behavioral tests over one year. The KI/KI and KI/KO
mice have overall normal balance, muscle strength and general locomotion.
Cerebral and cerebellar Luxol Fast Blue staining and measurement of levels of
myelin proteins showed no significant differences between the three groups,
suggesting that myelination is not overtly impaired in Polr3a KI/KI and KI/KO
mice. Finally, expression levels of several Pol III transcripts in the brain
showed no statistically significant differences. We conclude that the first
transgenic mice with a leukodystrophy-causing Polr3a mutation do not recapitulate
the childhood-onset HLD observed in the majority of human patients with POLR3A
mutations, and provide essential information to guide selection of Polr3a
mutations for developing future mouse models of the disease.
PMID- 28407789
TI - Identification and functional characterisation of a Schistosoma japonicum insulin
like peptide.
AB - BACKGROUND: Previous studies have shown that insulin receptors in schistosomes,
triggered by host insulin, play an important role in parasite growth, development
and fecundity by regulating glucose metabolism. However, limited information is
available on the recently identified endogenous insulin-like peptide (ILP) in
blood flukes. RESULTS: We isolated ILPs from Schistosoma japonicum (SjILP) and S.
recognised (SmILP) and present results of their molecular and structural
analysis. SjILP shares 63% amino acid identity with SmILP, but only 18% identity
with human insulin. There is high cross immunological reactivity between the S.
japonicum and S. mansoni ILPs as observed in western blots using an anti-SjILP
polyclonal antibody. ADP binding/hydrolysis ability was observed in both SjILP
and SmILP, but not in human insulin, suggesting a parasite-specific role for ILP
compared with host insulin. Protein binding assays using the Octet-RED system
showed SjILP binds S. japonicum IRs (SjIR1 and SjIR2) strongly. An anti-phospho
antibody against extracellular signal-regulated kinase (Erk) recognised a 44-kDa
target band in an extract of adult worms after stimulation by rSjILP in vitro,
suggesting an important role for SjILP in activating SjIRs and in regulating
downstream signal transduction. Immunolocalisation showed SjILP is located on the
tegument and the underlying musculature, similar to that observed for SjIR1, but
it is also present throughout the parenchyma of males and in the vitelline cells
of females, the same locations as SjIR2 described in an earlier published study
of ours. The same localisation of SjILP and the SjIRs is suggestive of an
interaction between the insulin-like peptide and the IRs. In addition to binding
host insulin, schistosomes also can express their own endogenous ILPs, which can
activate the parasite insulin signal pathway, thereby playing a critical role in
worm growth, development and fertility. CONCLUSIONS: These findings shed new
light on ILPs in schistosomes, providing further insight into the distinct and
specialised functions of SjIR1 and 2 in S. japonicum and their interaction with
host insulin.
PMID- 28407790
TI - Ultrastructure and localization of Neorickettsia in adult digenean trematodes
provides novel insights into helminth-endobacteria interaction.
AB - BACKGROUND: Neorickettsia are a group of intracellular alpha proteobacteria
transmitted by digeneans (Platyhelminthes, Trematoda). These endobacteria can
also infect vertebrate hosts of the helminths and cause serious diseases in
animals and humans. Neorickettsia have been isolated from infected animals and
maintained in cell cultures, and their morphology in mammalian cells has been
described. However, limited information is available on the morphology and
localization of Neorickettsia in the trematode host. METHODS: We used a
Neorickettsia-infected strain of the model trematode Plagiorchis elegans to
infect Syrian Golden hamsters to produce adult worms. Ultrastructure of
Neorickettsia was assessed by transmission electron microscopy of high pressure
freezing/freeze substitution fixed specimens. A Neorickettsia surface protein
from P. elegans (PeNsp-3) was cloned and antibodies against the recombinant
protein were used to localize Neorickettsia by immunohistochemistry. RESULTS:
Ultrastructural analysis revealed moderate numbers of pleomorphic endobacteria
with a median size of 600 * 400 nm and characteristic double membranes in various
tissue types. Endobacteria showed tubular membrane invaginations and secretion of
polymorphic vesicles. Endobacteria were unevenly localized as single cells, or
less frequently as small morula-like clusters in the ovary, Mehlis' gland,
vitelline follicles, uterus, intrauterine eggs, testis, cirrus-sac, tegument,
intestine and the oral and ventral sucker. Examination of hamster small intestine
infected with P. elegans showed many endobacteria at the host-parasite interface
such as the oral and ventral sucker, the tegument and the excretory pore.
CONCLUSIONS: We conclude that adult P. elegans trematodes carry Neorickettsia
endobacteria in varying numbers in many tissue types that support vertical
transmission, trematode to trematode transmission via seminal fluid, and possibly
horizontal transmission from trematodes to vertebrate hosts. These means appear
to be novel mechanisms of pathogen transmission by endoparasitic worms.
PMID- 28407791
TI - Accelerated differentiation of human induced pluripotent stem cells to blood
brain barrier endothelial cells.
AB - BACKGROUND: Due to their ability to limitlessly proliferate and specialize into
almost any cell type, human induced pluripotent stem cells (iPSCs) offer an
unprecedented opportunity to generate human brain microvascular endothelial cells
(BMECs), which compose the blood-brain barrier (BBB), for research purposes.
Unfortunately, the time, expense, and expertise required to differentiate iPSCs
to purified BMECs precludes their widespread use. Here, we report the use of a
defined medium that accelerates the differentiation of iPSCs to BMECs while
achieving comparable performance to BMECs produced by established methods.
METHODS: Induced pluripotent stem cells were seeded at defined densities and
differentiated to BMECs using defined medium termed E6. Resultant purified BMEC
phenotypes were assessed through trans-endothelial electrical resistance (TEER),
fluorescein permeability, and P-glycoprotein and MRP family efflux transporter
activity. Expression of endothelial markers and their signature tight junction
proteins were confirmed using immunocytochemistry. The influence of co-culture
with astrocytes and pericytes on purified BMECs was assessed via TEER
measurements. The robustness of the differentiation method was confirmed across
independent iPSC lines. RESULTS: The use of E6 medium, coupled with updated
culture methods, reduced the differentiation time of iPSCs to BMECs from thirteen
to 8 days. E6-derived BMECs expressed GLUT-1, claudin-5, occludin, PECAM-1, and
VE-cadherin and consistently achieved TEER values exceeding 2500 Omega * cm2
across multiple iPSC lines, with a maximum TEER value of 4678 +/- 49 Omega * cm2
and fluorescein permeability below 1.95 * 10-7 cm/s. E6-derived BMECs maintained
TEER above 1000 Omega * cm2 for a minimum of 8 days and showed no statistical
difference in efflux transporter activity compared to BMECs differentiated by
conventional means. The method was also found to support long-term stability of
BMECs harboring biallelic PARK2 mutations associated with Parkinson's Disease.
Finally, BMECs differentiated using E6 medium responded to inductive cues from
astrocytes and pericytes and achieved a maximum TEER value of 6635 +/- 315 Omega
* cm2, which to our knowledge is the highest reported in vitro TEER value to
date. CONCLUSIONS: Given the accelerated differentiation, equivalent performance,
and reduced cost to produce BMECs, our updated methods should make iPSC-derived
in vitro BBB models more accessible for a wide variety of applications.
PMID- 28407792
TI - Treatment of post-anesthesia dementia with perispinal etanercept injection and
hyperbaric oxygen therapy: a case report.
AB - BACKGROUND: We report on the first case of successful treatment for post
anesthesia dementia with perispinal etanercept injection combined with hyperbaric
oxygen therapy. CASE PRESENTATION: Our patient was a 77-year-old Caucasian man of
Mexican ethnicity who presented to our clinic 4.5 years after a knee replacement
surgery. Immediately post-surgery, the patient began to show dramatic cognitive,
physical, and emotional impairment compared with his presurgical state; these
symptoms were still present when he arrived at our clinic. A clinical assessment
and brain single-photon emission computer tomography were performed. Diagnoses of
dementia with major cognitive deficits and aphasia were established. A 40-session
course of hyperbaric oxygen therapy was initiated to address our patient's
impairments. After the first ten hyperbaric oxygen therapy treatments, our
patient was administered 25 mg perispinal etanercept injections approximately
once weekly for 5 months. Starting after the first perispinal etanercept
injection, our patient began showing progressive improvements. By the 5-month
follow-up, his cognitive and physical function were substantially restored. A
follow-up single-photon emission computer tomography scan showed increased
perfusion in several small, localized areas. CONCLUSIONS: In this case of
dementia and major cognitive disorder post major surgery and anesthesia, the very
beneficial effect of combining hyperbaric oxygen therapy with perispinal
etanercept is outlined.
PMID- 28407793
TI - The diagnosis and management of the Spitz nevus in the pediatric population: a
systematic review and meta-analysis protocol.
AB - BACKGROUND: Spitz nevi are uncommon melanocytic neoplasms found in children.
Historically, the diagnosis and management of these tumors has lacked consensus
among oncologists, pathologists, plastic surgeons, and dermatologists. Once
interpreted and treated as a "juvenile melanoma", many have argued for the
benignancy of such tumors in certain patient age groups, encouraging a
conservative approach. The lack of consensus surrounding the diagnosis and
perceived malignant potential of these tumors has led physicians to approach them
on a case-by-case basis and institutional protocols. To date, no evidence-based
management guideline exists. The objective of this systematic review is to both
collect and appraise the evidence on the diagnosis and management of these
tumors. METHODS: A comprehensive electronic literature search will be conducted
in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to December
2016. Our search involved collaborating with a healthcare librarian to create a
strategy for the OVID/MEDLINE databases. A search of electronic databases for
oncology, pathology, plastic surgery, and dermatology abstracts will be
performed. Key search terms will include, among several others, "Spitz nevi,"
"Spitzoid melanoma," "juvenile tumor," and "pediatric". The language of
publication will be restricted to English and French. Wherever data allows, meta
analyses will be used to assess differences between Spitz nevi and the tumor of
comparison. Additionally, data extraction and summarization using tables will be
performed. This review has been registered with PROSPERO (CRD42016034045).
CONCLUSIONS: This review will systematically and comprehensively review
diagnostic and management practices associated with the Spitz nevus. This
overview of current literature will hopefully provide the foundation for future
standardization of clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42016034045.
PMID- 28407794
TI - Barriers to and facilitators of hypertension management in Asmara, Eritrea:
patients' perspectives.
AB - BACKGROUND: Personal hypertension management is a cornerstone in the prevention
of hypertension complications. In Eritrea, the increase in the national life
expectancy rate has been accompanied by an increase in hypertension complications
such as stroke. Hence, this study was designed to identify barriers and
facilitates to hypertension management from the perspective of the patients.
METHODS: This was a qualitative study of a total of 48 individual in-depth
interviews and two focus group discussions. It was conducted among hypertensive
patients who were attending outpatient services at two hospitals in Asmara,
Eritrea. RESULTS: This study identified barriers and facilitators of hypertension
management related to the individual patient, family and community, and
healthcare system. With respect to individual factors, economic barriers, stress,
non-adherence to medications due to the use of traditional remedies, and
difficulties and misconceptions about following physical activity guidelines were
mentioned as barriers to hypertension management. Related to the community and
healthcare system, low community awareness, community stigma, and inadequate
health promotion materials were stated as barriers. Individual knowledge, family,
and government support were reported as very important factors to the patient's
success in the personal hypertension management. CONCLUSIONS: Counseling patients
about adherence to medication, strengthening family and government support, and
empowering families and the community with appropriate knowledge of hypertension
management could potentially help in an individual's adherence.
PMID- 28407795
TI - The association between self-rated health and different anthropometric and body
composition measures in the Chinese population.
AB - BACKGROUND: To analyze the strength of association between self-rated health and
six anthropometric and body composition measures to explore the best indicator.
METHODS: Analyses were based on the cross-sectional data from the China Kadoorie
Biobank Study and approximately 300,000 adults were analyzed. Logistics
regression was used to analyze the association between self-rated health (good or
poor) and anthropometric and body composition measures (height, weight, body mass
index (BMI), waist circumference (WC), hip circumference (HC) and body fat
percentage, waist-to-hip ratio and waist-to-height ratio). Stratified analyses
were undertaken to understand the effect modification of socioeconomic status on
the association. RESULT: Odds ratio of self-rated better health had an inverted U
shape association with weight, BMI, WC and body fat, with weight levels
increasing until around 73.8 and 65.7 kg for male and female, BMI around 26.8
kg/m2, WC around 85.8 and 87.6 cm, body fat around 24.3 and 36.3%, and then
declining thereafter. Height and HC also indicated a slightly inverted U-shape
association. The strongest association was observed after adjustment was weight,
with one standard deviation greater weight associated with 10.2% and 10.6%
increased odds in male and female. CONCLUSIONS: Being underweight and overweight
are both risk factors for poor self-rated health in males and females, and weight
is the best indicator of self-rated health compared with other measures.
PMID- 28407796
TI - Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection and
the molecular characteristics of MRSA bacteraemia over a two-year period in a
tertiary teaching hospital in Malaysia.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an established
pathogen that causes hospital- and community-acquired infections worldwide. The
prevalence rate of MRSA infections were reported to be the highest in Asia. As
there is limited epidemiological study being done in Malaysia, this study aimed
to determine the prevalence of MRSA infection and the molecular characteristics
of MRSA bacteraemia. METHODS: Two hundred and nine MRSA strains from year 2011 to
2012 were collected from a tertiary teaching hospital in Malaysia. The strains
were characterized by antimicrobial susceptibility testing, staphylococcal
cassette chromosome mec (SCCmec) typing, detection of Panton-Valentine leukocidin
(PVL) gene, multilocus sequence typing (MLST) and pulsed-field gel
electrophoresis (PFGE). Patient's demographic and clinical data were collected
and correlated with molecular data by statistical analysis. RESULTS: Male gender
and patient >50 years of age (p < 0.0001) were significantly associated with the
increased risk of MRSA acquisition. Fifty-nine percent of MRSA strains were HA
MRSA that carried SCCmec type II, III, IV and V while 31% were CA-MRSA strains
with SCCmec III, IV and V. The prevalence of PVL gene among 2011 MRSA strains was
5.3% and no PVL gene was detected in 2012 MRSA strains. All of the strains were
sensitive to vancomycin. However, vancomycin MIC creep phenomenon was
demonstrated by the increased number of MRSA strains with MIC >=1.5 MUg/mL (p =
0.008) between 2011 and 2012. Skin disease (p = 0.034) and SCCmec type III (p =
0.0001) were found to be significantly associated with high vancomycin MIC. Forty
four percent of MRSA strains from blood, were further subtyped by MLST and PFGE.
Most of the bacteraemia cases were primary bacteraemia and the common
comorbidities were diabetes, hypertension and chronic kidney disease. The
predominant pulsotype was pulsotype C exhibited by SCCmec III-ST239. This is a
first study in Malaysia that reported the occurrence of MRSA clones such as
SCCmec V-ST5, untypeable-ST508, SCCmec IV-ST1 and SCCmec IV-ST1137. CONCLUSIONS:
SCCmec type III remained predominant among the MRSA strains in this hospital. The
occurrence of SCCmec IV and V among hospital strains and the presence of SCCmec
III in CA-MRSA strains are increasing. MRSA strains causing bacteraemia over the
two-year study period were found to be genetically diverse.
PMID- 28407797
TI - Association between length of residence and overweight among adult immigrants in
Portugal: A nationwide cross-sectional study.
AB - BACKGROUND: Despite the importance of immigrant population in Portugal few
studies have analyzed the patterns of overweight/obesity in this subpopulation.
The aims of this study are: (i) describe and compare the prevalence of overweight
between immigrants and natives in Portugal; (ii) analyze the association between
length of residence and overweight among adult immigrants in Portugal. METHODS: A
cross-sectional study (2005-2006) in a representative sample of the Portuguese
population from national territory, including the Autonomous Regions of Azores
and Madeira. The final sample comprised 31,685 adult participants (>=19 years
old), of whom 4.6% were immigrants. Country of birth was used to determine
immigrant condition. Logistic regressions were conducted to investigate the
association between overweight (dependent variable) and length of residence
(exposure), adjusting for all covariates in the study. A 5% confidence level and
95% CI were considered. RESULTS: The percentage of immigrants that are overweight
[44.9% (95% CI: 42.3; 47.5)] was lower than for natives [52.8% (95% CI: 52.2;
53.4)]. The migrant condition, after adjusted for sociodemographic variables, was
not associated with overweight [OR 1.004 (95% CI: 0.998; 1.010)]. Among
immigrants, being women [OR 0.585 (95% CI: 0.583; 0.587)], not married [OR 0.784
(95% CI: 0.781; 0.787)] and with a higher education [OR 0.481 (95% CI: 0.478;
0.483)], are probably protective factors of being overweight. Adjusting for other
factors, the odds of being overweight for a long-term immigrant (>=15 years) was
1.3 times higher [OR 1.274 (95% CI: 1.250; 1.299)] than for the newcomers (<4
years). CONCLUSIONS: The prevalence of overweight was higher for natives than
immigrants. Length of residence (>=15 years) was positively associated with
prevalence of overweight, among adult immigrant population. In the future,
understanding dietary patterns and acculturation process may be important for
health immigrant studies.
PMID- 28407798
TI - Utilization of defined microbial communities enables effective evaluation of meta
genomic assemblies.
AB - BACKGROUND: Metagenomics is the study of the microbial genomes isolated from
communities found on our bodies or in our environment. By correctly determining
the relation between human health and the human associated microbial communities,
novel mechanisms of health and disease can be found, thus enabling the
development of novel diagnostics and therapeutics. Due to the diversity of the
microbial communities, strategies developed for aligning human genomes cannot be
utilized, and genomes of the microbial species in the community must be assembled
de novo. However, in order to obtain the best metagenomic assemblies, it is
important to choose the proper assembler. Due to the rapidly evolving nature of
metagenomics, new assemblers are constantly created, and the field has not yet
agreed on a standardized process. Furthermore, the truth sets used to compare
these methods are either too simple (computationally derived diverse communities)
or complex (microbial communities of unknown composition), yielding results that
are hard to interpret. In this analysis, we interrogate the strengths and
weaknesses of five popular assemblers through the use of defined biological
samples of known genomic composition and abundance. We assessed the performance
of each assembler on their ability to reassemble genomes, call taxonomic
abundances, and recreate open reading frames (ORFs). RESULTS: We tested five
metagenomic assemblers: Omega, metaSPAdes, IDBA-UD, metaVelvet and MEGAHIT on
known and synthetic metagenomic data sets. MetaSPAdes excelled in diverse sets,
IDBA-UD performed well all around, metaVelvet had high accuracy in high abundance
organisms, and MEGAHIT was able to accurately differentiate similar organisms
within a community. At the ORF level, metaSPAdes and MEGAHIT had the least number
of missing ORFs within diverse and similar communities respectively. CONCLUSIONS:
Depending on the metagenomics question asked, the correct assembler for the task
at hand will differ. It is important to choose the appropriate assembler, and
thus clearly define the biological problem of an experiment, as different
assemblers will give different answers to the same question.
PMID- 28407799
TI - Seroprevalence of a "new" bacterium, Simkania negevensis, in renal transplant
recipients and in hemodialysis patients.
AB - BACKGROUND: Simkania negevensis is an obligate intracellular bacterium belonging
to the family Simkaniaceae in the Chlamydiales order. It is considered an
ubiquitous microorganism and aquatic environments may be involved as a source of
infection for humans. It was just isolated in samples from domestic water
supplies and from mains water supplies, like spa water or swimming pool water,
confirming its ability to resist to the common chlorination treatments. Evidence
indicates a possible role of the microorganism in respiratory tract infections,
in gastroenteric disorders and in the pathogenesis of cardiovascular disease,
furthermore it has hypothesized that it could play a role in lung transplant
rejection. Prevalence and possible effects in nephrology are unknown. METHODS: We
examined the occurrence of Simkania negevensis in two differents populations,
both characterized by a high susceptibility to infectious complications: 105
hemodialysis patients, 105 renal transplant recipients and 105 healthy subjects
through the IgG and IgA response to Simkania negevensis in their sera. Serum
antibodies to Simkania negevensis were detected by a homemade ELISA performed
according to the Kahane's protocol. Furthermore water samples from hemodialytic
circuit were collected, to evaluate Simkania negevensis resistance to usual
treatment of disinfection. RESULTS: Our results were unexpected, showing a higher
seroprevalence of antibodies against Simkania negevensis in the hemodialysis
patients, compared to renal transplant patients (IgG 22% vs 9% - IgA 9% vs 3%).
S. negevensis was isolated in all water samples analyzed. CONCLUSIONS: Our study
detected for the first time the occurrence of S. negevensis in hemodialysis and
in renal transplant patients. Our findings suggest that water used in
hemodialysis could be one of the possible sources of S. negevensis infection,
without clinical involvement risk for patients.
PMID- 28407800
TI - Advance directives and power of attorney for health care in the oldest-old -
results of the AgeQualiDe study.
AB - BACKGROUND: Completion of advance directives (ADs) and power of attorney (POA)
documents may protect a person's autonomy in future health care situations when
the individual lacks decisional capacity. As such situations become naturally
much more common in old age, we specifically aimed at providing information on
(i) the frequency of ADs/POA in oldest-old individuals and (ii) factors
associated with having completed ADs/POA. METHODS: We analyzed data of oldest-old
primary care patients (85+ years; including community-dwelling and
institutionalized individuals) within the German AgeQualiDe study. Patients were
initially recruited via their general practitioners (GPs). We calculated
frequencies of ADs and POA for health care with 95% confidence intervals (CI) and
used multivariable logistic regression analysis to evaluate the association
between having ADs and POA and participants' socio-demographic, cognitive,
functional, and health-related characteristics. RESULTS: Among 868 GP patients
participating in AgeQualiDe (response = 90.9%), n = 161 had dementia and n = 3
were too exhausted/ill to answer the questions. Out of the remaining 704 (81.1%)
dementia-free patients (mean age = 88.7 years; SD = 3.0), 69.0% (95%-CI = 65.6
72.4) stated to having ADs and 64.6% (95%-CI = 61.1-68.2) to having a POA for
health care. Individual characteristics did not explain much of the variability
of the presence/absence of ADs and POA (regression models: Nagelkerke's R2 =
0.034/0.051). The most frequently stated reasons for not having ADs were that the
older adults trust their relatives or physicians to make the right decisions for
them when necessary (stated by 59.4% and 44.8% of those without ADs). Among the
older adults with ADs, the majority had received assistance in its preparation
(79.0%), most frequently from their children/grandchildren (38.3%).
Children/grandchildren were also the most frequently stated group of designated
persons (76.7%) for those with a POA for health care. CONCLUSIONS: Our findings
suggest a high dissemination of ADs and POA for health care in the oldest-old in
Germany. Some adults without ADs/POA perhaps would have completed advance care
documents, if they had had received more information and support. When planning
programs to offer advanced care planning to the oldest old, it might be helpful
to respond to these specific needs, and also to be sensitive to attitudinal
differences in this target group.
PMID- 28407801
TI - Single-base resolution methylomes of upland cotton (Gossypium hirsutum L.) reveal
epigenome modifications in response to drought stress.
AB - BACKGROUND: DNA methylation, with a cryptic role in genome stability, gene
transcription and expression, is involved in the drought response process in
plants, but the complex regulatory mechanism is still largely unknown. RESULTS:
Here, we performed whole-genome bisulfite sequencing (WGBS) and identified long
non-coding RNAs on cotton leaves under drought stress and re-watering treatments.
We obtained 31,223 and 30,997 differentially methylated regions (representing
2.48% of the genome) after drought stress and re-watering treatments,
respectively. Our data also showed that three sequence contexts, including mCpG,
mCHG, mCHH, all presented a hyper-methylation pattern under drought stress and
were nearly restored to normal levels after the re-watering treatment. Among all
the methylation variations, asymmetric CHH methylation was the most consistent
with external environments, suggesting that methylation/demethylation in a CHH
context may constitute a novel epigenetic modification in response to drought
stress. Combined with the targets of long non-coding RNAs, we found that long non
coding RNAs may mediate variations in methylation patterns by splicing into
microRNAs. Furthermore, the many hormone-related genes with methylation
variations suggested that plant hormones might be a potential mechanism in the
drought response. CONCLUSIONS: Future crop-improvement strategies may benefit by
taking into account not only the DNA genetic variations in cotton varieties but
also the epigenetic modifications of the genome.
PMID- 28407802
TI - A prediction model for lymph node metastases using pathologic features in
patients intraoperatively diagnosed as stage I non-small cell lung cancer.
AB - BACKGROUND: There is little information on which pattern should be chosen to
perform lymph node dissection for stage I non-small-cell lung cancer. This study
aimed to develop a model for predicting lymph node metastasis using pathologic
features of patients intraoperatively diagnosed as stage I non-small-cell lung
cancer. METHODS: We collected pathology data from 284 patients intraoperatively
diagnosed as stage I non-small-cell lung cancer who underwent lobectomy with
complete lymph node dissection from 2013 through 2014, assessing various factors
for an association with metastasis to lymph nodes (age, gender, pathology, tumour
location, tumour differentiation, tumour size, pleural invasion, bronchus
invasion, multicentric invasion and angiolymphatic invasion). After analysing
these variables, we developed a multivariable logistic model to estimate risk of
metastasis to lymph nodes. RESULTS: Univariate logistic regression identified
tumour size >2.65 cm (p < 0.001), tumour differentiation (p < 0.001), pleural
invasion (p = 0.034) and bronchus invasion (p < 0.001) to be risk factors
significantly associated with the presence of metastatic lymph nodes. On
multivariable analysis, only tumour size >2.65 cm (p < 0.001), tumour
differentiation (p = 0.006) and bronchus invasion (p = 0.017) were independent
predictors for lymph node metastasis. We developed a model based on these three
pathologic factors that determined that the risk of metastasis ranged from 3% to
44% for patients intraoperatively diagnosed as stage I non-small-cell lung
cancer. By applying the model, we found that the values y > 0.80, 0.43 < y <=
0.80, y <= 0.43 plus tumour size >2 cm and y <=0.43 plus tumour size <=2 cm
yielded positive lymph node metastasis predictive values of 44%, 18%, 14% and 0%,
respectively. CONCLUSIONS: A non-invasive prediction model including tumour size,
tumour differentiation and bronchus invasion may be useful to give thoracic
surgeons recommendations on lymph node dissection for patients intraoperatively
diagnosed as Stage I non-small cell lung cancer.
PMID- 28407803
TI - Orchitis reveals an extragonadal primary mediastinal thymic seminoma: a
coincidence or not?
AB - BACKGROUND: Mediastinal thymic seminomas are rare male germ cell tumors with
extragonadal origin that appear predominately with a cystic appearance. CASE
PRESENTATION: A 22-year-old male was referred to our department for further
investigation of a mediastinal mass discovered incidentally during routine chest
X-ray. The patient has denied any symptoms including dyspnea, chest pain, cough,
fever, dysphagia, hemoptysis, weight loss, and weakness. His past medical history
was remarkable for orchitis, for which he had undergone a bilateral testicular
biopsy, without the latter however, indicating the presence of a germ cell tumor
or a premalignant lesion. Contrast-enhanced chest computed tomography revealed a
lobulated and well-marginated cystic lesion in the anterior mediastinum.
Differential diagnosis included mostly a multilocular thymic cyst, a lymphoma, a
seminoma, or a soft tissue tumor. Resection of the mass revealed a primary thymic
seminoma. CONCLUSIONS: A surgical approach for the management of these tumors
might be reasonable considering that an extensive sampling is mandatory to gain
an appropriate biopsy preoperatively in order to securely confirm or refute the
presence of a mediastinal extragonadal tumor. Orchitis might be a sign of a
general disorder of the germ cells which might transform in time.
PMID- 28407804
TI - Mathematical model of TGF-betasignalling: feedback coupling is consistent with
signal switching.
AB - BACKGROUND: Transforming growth factor beta (TGF-beta) signalling regulates the
development of embryos and tissue homeostasis in adults. In conjunction with
other oncogenic changes, long-term perturbation of TGF-beta signalling is
associated with cancer metastasis. Although TGF-beta signalling can be complex,
many of the signalling components are well defined, so it is possible to develop
mathematical models of TGF-beta signalling using reduction and scaling methods.
The parameterization of our TGF-beta signalling model is consistent with
experimental data. RESULTS: We developed our mathematical model for the TGF-beta
signalling pathway, i.e. the RF- model of TGF-beta signalling, using the "rapid
equilibrium assumption" to reduce the network of TGF-beta signalling reactions
based on the time scales of the individual reactions. By adding time-delayed
positive feedback to the inherent time-delayed negative feedback for TGF-beta
signalling. We were able to simulate the sigmoidal, switch-like behaviour
observed for the concentration dependence of long-term (> 3 hours) TGF-beta
stimulation. Computer simulations revealed the vital role of the coupling of the
positive and negative feedback loops on the regulation of the TGF-beta signalling
system. The incorporation of time-delays for the negative feedback loop improved
the accuracy, stability and robustness of the model. This model reproduces both
the short-term and long-term switching responses for the intracellular signalling
pathways at different TGF-beta concentrations. We have tested the model against
experimental data from MEF (mouse embryonic fibroblasts) WT, SV40-immortalized
MEFs and Gp130 F/F MEFs. The predictions from the RF- model are consistent with
the experimental data. CONCLUSIONS: Signalling feedback loops are required to
model TGF-beta signal transduction and its effects on normal and cancer cells. We
focus on the effects of time-delayed feedback loops and their coupling to ligand
stimulation in this system. The model was simplified and reduced to its key
components using standard methods and the rapid equilibrium assumption. We
detected differences in short-term and long-term signal switching. The results
from the RF- model compare well with experimental data and predict the dynamics
of TGF-beta signalling in cancer cells with different mutations.
PMID- 28407806
TI - Development and validation of classifiers and variable subsets for predicting
nursing home admission.
AB - BACKGROUND: In previous years a substantial number of studies have identified
statistically important predictors of nursing home admission (NHA). However, as
far as we know, the analyses have been done at the population-level. No prior
research has analysed the prediction accuracy of a NHA model for individuals.
METHODS: This study is an analysis of 3056 longer-term home care customers in the
city of Tampere, Finland. Data were collected from the records of social and
health service usage and RAI-HC (Resident Assessment Instrument - Home Care)
assessment system during January 2011 and September 2015. The aim was to find out
the most efficient variable subsets to predict NHA for individuals and validate
the accuracy. The variable subsets of predicting NHA were searched by sequential
forward selection (SFS) method, a variable ranking metric and the classifiers of
logistic regression (LR), support vector machine (SVM) and Gaussian naive Bayes
(GNB). The validation of the results was guaranteed using randomly balanced data
sets and cross-validation. The primary performance metrics for the classifiers
were the prediction accuracy and AUC (average area under the curve). RESULTS: The
LR and GNB classifiers achieved 78% accuracy for predicting NHA. The most
important variables were RAI MAPLE (Method for Assigning Priority Levels),
functional impairment (RAI IADL, Activities of Daily Living), cognitive
impairment (RAI CPS, Cognitive Performance Scale), memory disorders (diagnoses
G30-G32 and F00-F03) and the use of community-based health-service and prior
hospital use (emergency visits and periods of care). CONCLUSION: The accuracy of
the classifier for individuals was high enough to convince the officials of the
city of Tampere to integrate the predictive model based on the findings of this
study as a part of home care information system. Further work need to be done to
evaluate variables that are modifiable and responsive to interventions.
PMID- 28407805
TI - Revelation of mRNAs and proteins in porcine milk exosomes by transcriptomic and
proteomic analysis.
AB - BACKGROUND: Milk is a complex liquid that provides nutrition to newborns. Recent
reports demonstrated that milk is enriched in maternal-derived exosomes that are
involved in fetal physiological and pathological conditions by transmission of
exosomal mRNAs, miRNAs and proteins. Until now, there is no such research
relevant to exosomal mRNAs and proteins in porcine milk, therefore, we have
attempted to investigate porcine milk exosomal mRNAs and proteins using RNA
sequencing and proteomic analysis. RESULTS: A total of 16,304 (13,895 known and
2, 409 novel mRNAs) mRNAs and 639 (571 known, 66 candidate and 2 putative
proteins) proteins were identified. GO and KEGG annotation indicated that most
proteins were located in the cytoplasm and participated in many immunity and
disease-related pathways, and some mRNAs were closely related to metabolisms,
degradation and signaling pathways. Interestingly, 19 categories of proteins were
tissue-specific and detected in placenta, liver, milk, plasma and mammary. COG
analysis divided the identified mRNAs and proteins into 6 and 23 categories,
respectively, 18 mRNAs and 10 proteins appeared to be involved in cell cycle
control, cell division and chromosome partitioning. Additionally, 14 selected
mRNAs were identified by qPCR, meanwhile, 10 proteins related to immunity and
cell proliferation were detected by Western blot. CONCLUSIONS: These results
provide the first insight into porcine milk exosomal mRNA and proteins, and will
facilitate further research into the physiological significance of milk exosomes
for infants.
PMID- 28407807
TI - Subclinical inflammation associated with prolonged TIMP-1 upregulation and
arterial stiffness after gestational diabetes mellitus: a hospital-based cohort
study.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) has significant implications for
the future health of the mother. Some clinical studies have suggested subclinical
inflammation and vascular dysfunction after GDM. We aimed to study whether
concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor
of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as
well as values of arterial stiffness differ between women with and without a
history of GDM a few years after delivery. We also investigated possible effects
of obesity on the results. METHODS: We studied two cohorts-120 women with a
history of GDM and 120 controls-on average 3.7 years after delivery. Serum
concentrations of hsCRP were determined by immunonephelometric and
immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and
TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was
determined using the foot-to-foot velocity method from carotid and femoral
waveforms by using a SphygmoCor device. Arterial compliance was measured non
invasively by an HDI/PulseWaveTMCR-2000 arterial tonometer. All 240 women were
also included in subgroup analyses to study the effect of obesity on the results.
Multiple linear regression analyses were performed with adjustment for
confounding factors. RESULTS: PWV after pregnancy complicated by GDM was
significantly higher than after normal pregnancy, 6.44 +/- 0.83 (SD) vs. 6.17 +/-
0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants
of PWV in multiple linear regression analyses. On the other hand, compliance
indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ
between the study cohorts. Serum TIMP-1 levels were significantly increased after
previous GDM (p = 0.020). However, no differences were found in the serum levels
of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher
concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women
compared with non-obese ones. CONCLUSIONS: PWV values were significantly higher
after GDM compared with normoglycemic pregnancies and were associated with
prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in
participants with high BMI than in those with previous GDM.
PMID- 28407809
TI - Merger of two dispatch centres: does it improve quality and patient safety?
AB - BACKGROUND: Dispatch centres (DCs) are considered an essential but expensive
component of many highly developed healthcare systems. The number of DCs in a
country, region, or state is usually based on local history and often related to
highly decentralised healthcare systems. Today, current technology (Global
Positioning System or Internet access) abolishes the need for closeness between
DCs and the population. Switzerland went from 22 DCs in 2006 to 17 today. This
study describes from a quality and patient safety point of view the merger of two
DCs. METHODS: The study analysed the performance (over and under-triage) of two
medical DCs for 12 months prior to merging and for 12 months again after the
merger in 2015. Performance was measured comparing the priority level chosen by
dispatcher and the severity of cases assessed by paramedics on site using the
National Advisory Committee for Aeronautics (NACA) score. We ruled that NACA
score > 3 (injuries/diseases which can possibly lead to deterioration of vital
signs) to 7 (lethal injuries/diseases) should require a priority dispatch with
lights and siren (L&S). While NACA score < 4 should require a priority dispatch
without L&S. Over-triage was defined as the proportion of L&S dispatches with a
NACA score < 4, and under-triage as the proportion of dispatches without L&S with
a NACA > 3. RESULTS: Prior to merging, Dispatch A had a sensitivity/specificity
regarding the use of lights and sirens and severity of cases of 86%/48% with over
and under-triage rates of 78% and 5%, respectively. Dispatch B had sensitivity
and specificity of 92%/20% and over- and under-triage rates of 84% and 7%,
respectively. After they merged, global sensitivity/specificity reached 87%/67%,
and over- and under-triage rates were 71% and 3%, respectively CONCLUSIONS: A
part the potential cost advantage achieved by the merger of two DCs, it can
improve the quality of services to the population, reducing over- and under
triage and the use of lights and sirens and therefore, the risk of accidents.
This is especially the case when a DC with poor triage performance merges with a
high-performing DC.
PMID- 28407808
TI - Nested-PCR assay for detection of Schistosoma japonicum infection in domestic
animals.
AB - BACKGROUND: Schistosomiasis japonica is a common zoonosis. Domestic animals are
the primary source of infection and play an important role in disease
transmission. The prevalence and infectivity of this disease in domestic animals
in China have significantly decreased and, for this reason, diagnostics with a
higher sensitivity have become increasingly necessary. It was reported that
polymerase chain reaction (PCR)-based methods could be used to detect schistosome
infection in humans and animals and presented a high sensitivity and specificity.
The present study aimed to develop a PCR-based method for detection of
Schistosoma japonicum infection in domestic animals. METHODS: A specific nested
PCR assay was developed to detect S. japonicum infection in domestic animals via
amplification of a 231-bp DNA fragment of retrotransposon SjR2. The developed
assay was first used in sera and dry blood filter paper (DBFP) from goats and
buffaloes at different time points of infection. Then, 78 DBFPs from 39
artificially-infected bovines at 14 and 28 days post-infection and 42 DBFPs from
schistosome-negative bovines from the city of Huangshan in the Anhui province
were used to evaluate the diagnostic validity. Furthermore, this assay was used
to detect S. japonicum infection in domestic animals in Dongzhi and Wangjiang
counties. RESULTS: The expected PCR product was detected in eggs and adult worms
of S. japonicum and blood samples from S. japonicum-infected goats and water
buffaloes, but not from Fasciola and Haemonchus contortus worms. The nested-PCR
assay could detect the target S. japonicum DNA in DBFPs from goats and buffaloes
after day 3 post-infection. The sensitivity in buffaloes at 14 and 28 days post
infection was 92.30% (36/39) and 100% (39/39), respectively. The specificity was
97.60% (41/42). The positivity rates in Dongzhi and Wangjiang counties were 6.00%
and 8.00% in bovines and 22.00% and 16.67% in goats, respectively. The positivity
rates in goats in both counties were higher than those in bovines with a
significant difference in Dongzhi County but not in Wangjiang County (P < 0.05
and P = 0.23, respectively). CONCLUSIONS: Our results suggest that the developed
nested-PCR assay may be used for the diagnosis of S. japonicum infection in
domestic animals, and the control of S. japonicum infection in goats should be
paid more attention.
PMID- 28407810
TI - Does task shifting yield cost savings and improve efficiency for health systems?
A systematic review of evidence from low-income and middle-income countries.
AB - BACKGROUND: Task shifting has become an increasingly popular way to increase
access to health services, especially in low-resource settings. Research has
demonstrated that task shifting, including the use of community health workers
(CHWs) to deliver care, can improve population health. This systematic review
investigates whether task shifting in low-income and middle-income countries
(LMICs) results in efficiency improvements by achieving cost savings. METHODS:
Using the PRISMA guidelines for systematic reviews, we searched PubMed, Embase,
CINAHL, and the Health Economic Evaluation Database on March 22, 2016. We
included any original peer-review articles that demonstrated cost impact of a
task shifting program in an LMIC. RESULTS: We identified 794 articles, of which
34 were included in our study. We found that substantial evidence exists for
achieving cost savings and efficiency improvements from task shifting activities
related to tuberculosis and HIV/AIDS, and additional evidence exists for the
potential to achieve cost savings from activities related to malaria, NCDs, NTDs,
childhood illness, and other disease areas, especially at the primary health care
and community levels. CONCLUSIONS: Task shifting presents a viable option for
health system cost savings in LMICs. Going forward, program planners should
carefully consider whether task shifting can improve population health and health
systems efficiency in their countries, and researchers should investigate whether
task shifting can also achieve cost savings for activities related to emerging
global health priorities and health systems strengthening activities such as
supply chain management or monitoring and evaluation.
PMID- 28407811
TI - Saline versus balanced crystalloids for intravenous fluid therapy in the
emergency department: study protocol for a cluster-randomized, multiple-crossover
trial.
AB - BACKGROUND: Prior studies in critically ill patients suggest the supra
physiologic chloride concentration of 0.9% ("normal") saline may be associated
with higher risk of renal failure and death compared to physiologically balanced
crystalloids. However, the comparative effects of 0.9% saline and balanced fluids
are largely unexamined among patients outside the intensive care unit, who
represent the vast majority of patients treated with intravenous fluids.
METHODS/DESIGN: This study, entitled Saline Against Lactated Ringer's or Plasma
Lyte in the Emergency Department (SALT-ED), is a pragmatic, cluster, multiple
crossover trial at a single institution evaluating clinical outcomes of adults
treated with 0.9% saline versus balanced crystalloids for intravenous fluid
resuscitation in the emergency department. All adults treated in the study
emergency department receiving at least 500 mL of isotonic crystalloid solution
during usual clinical care and subsequently hospitalized outside the intensive
care unit are included. Treatment allocation of 0.9% saline versus balanced
crystalloids is assigned by calendar month, with study patients treated during
the same month assigned to the same fluid type. The first month (January 2016)
was randomly assigned to balanced crystalloids, with each subsequent month
alternating between 0.9% saline and balanced crystalloids. For balanced
crystalloid treatment, clinicians can choose either Lactated Ringer's or Plasma
Lyte A(c). The study period is set at 16 months, which will result in an
anticipated estimated sample size of 15,000 patients. The primary outcome is
hospital-free days to day 28, defined as the number of days alive and out of the
hospital from the index emergency department visit until 28 days later. Major
secondary outcomes include proportion of patients who develop acute kidney injury
by creatinine measurements; major adverse kidney events by hospital discharge or
day 30 (MAKE30), which is a composite outcome of death, new renal replacement
therapy, and persistent creatinine elevation >200% of baseline; and in-hospital
mortality. DISCUSSION: This ongoing pragmatic trial will provide the most
comprehensive evaluation to date of clinical outcomes associated with 0.9% saline
compared to physiologically balanced fluids in patients outside the intensive
care unit. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02614040 . Registered on 18
November 2015.
PMID- 28407812
TI - Diagnostic antigens for visceral leishmaniasis: clarification of nomenclatures.
AB - BACKGROUND: Stimulated by the increasing recent use of 'K' or 'rK' nomenclature
for antigens reported for visceral leishmaniasis (VL) diagnostic serology, we
wished to give a chronological synopsis of their reporting and the potentially
confusing terminology. METHODS: The literature was examined for 'K' or 'rK'
terminology for VL diagnostic antigens, with emphasis on the original
publications in which terms were first used. RESULTS: A chronological account of
the first use of these 'K' and 'rK' nomenclatures was compiled. Since the
original use of this terminology in 1993 in the name rK39 for a Leishmania
antigen fragment, we found nine subsequent instances where 'K' or 'rK' have been
used to maintain consistency with this nomenclature. We also found instances
where there were ambiguities regarding reported strain name, origin and GenBank
accession numbers. CONCLUSIONS: We have documented here the uses in the
literature of the 'K' or 'rK' prefix for VL diagnostic antigen nomenclature. We
suggest that, to avoid confusion, the use of such nomenclature for future
antigens should either provide the logical derivation of the term or indicate
that the designation is entirely empirical.
PMID- 28407814
TI - Erratum to: Detecting gene signature activation in breast cancer in an absolute,
single-patient manner.
PMID- 28407813
TI - Adapting an adherence support workers intervention: engaging traditional healers
as adherence partners for persons enrolled in HIV care and treatment in rural
Mozambique.
AB - BACKGROUND: Systematic adaptation of evidence-informed interventions that
increase retention in care and improve adherence to antiretroviral therapy (ART)
are essential to ending the HIV epidemic in rural sub-Saharan Africa. We selected
and adapted an adherence support worker intervention employed in Malawi for use
by traditional healers in rural Mozambique. Given the levels of trust and
dependence previously expressed by persons living with HIV (PLHIV) for
traditional medicine, we adapted the program to engage traditional healers within
the allopathic health system. METHODS: Adaption followed a theoretically driven
approach to intervention adaption: the Assessment-Decision-Administration
Production-Topical Experts-Integration-Training-Testing (ADAPT-ITT) model. Three
rounds of performance feedback, based on theater presentations of the adapted
intervention for stakeholders and idea generation, were completed with 12 groups
from March to July 2016 to develop the final model. We offered healer support to
180 newly diagnosed HIV-infected patients. RESULTS: Traditional healers were an
acceptable group of community health workers to assist with patient adherence and
retention. Traditional healers, clinicians, and interested community members
suggested novel strategies to tailor the adherence support worker intervention,
revealing a local culture of HIV denialism, aversion to the health system, and
dislike of healthcare providers, as well as a preference for traditional
treatments. Proposed changes to the intervention included modifications to the
training language and topics, expanded community-based activities to support
acceptability of an HIV diagnosis and to facilitate partner disclosure, and
accompaniment to the health facility by healers to encourage delivery of
respectful clinical care. PLHIV, healers, and clinicians deemed the intervention
socially acceptable during focus groups. We subsequently recruited 180 newly
diagnosed HIV-infected patients into the program: 170 (94%) accepted.
CONCLUSIONS: Systematic translation of interventions, even between regions with
similar social and economic environments, is an important first step to
successful program implementation. Efforts previously limited to community health
workers can be tailored for use by traditional healers-an underutilized and often
maligned health workforce. It proved feasible to use theater-based performances
to demonstrate delivery of the intervention in low-literacy populations,
generating discussions about social norms, community concerns, and the merits of
an acceptable strategy to improve retention and adherence to ART.
PMID- 28407815
TI - Acute symptomatic peri-lead edema 33 hours after deep brain stimulation surgery:
a case report.
AB - BACKGROUND: Symptomatic peri-lead edema is a rare complication of deep brain
stimulation that has been reported to develop 4 to 120 days postoperatively. CASE
PRESENTATION: Here we report the case of a 63-year-old Hispanic man with an 8
year history of Parkinson's disease who underwent bilateral placement of
subthalamic nucleus deep brain stimulation leads and presented with acute,
symptomatic, unilateral, peri-lead edema just 33 hours after surgery.
CONCLUSIONS: We document a thorough radiographic time course showing the
evolution of these peri-lead changes and their regression with steroid therapy,
and discuss the therapeutic implications of these findings. We propose that the
unilateral peri-lead edema after bilateral deep brain stimulation is the result
of severe microtrauma with blood-brain barrier disruption. Knowledge of such
early manifestation of peri-lead edema after deep brain stimulation is critical
for ruling out stroke and infection and preventing unnecessary diagnostic testing
or hardware removal in this rare patient population.
PMID- 28407818
TI - [Clinical and pathological features and the misdiagnosis of childhood Alport
syndrome: a retrospective analysis of 91 cases].
AB - OBJECTIVE: To explore the clinical and pathological features and the diagnosis of
childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed
on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all
91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children
with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed
on 82 children. Mild to moderate mesangial proliferation was observed in 74
cases. Small amounts of immune complexes deposits in the glomerular mesangial
area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation,
thickening and layering were observed in 53 cases by electron microscopy (EM). In
63 cases receiving renal tissue type IV collagen alpha3 and alpha5 chain
immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL
AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as
AS by renal tissue type IV collagen alpha3 and alpha5 chain immunofluorescence,
21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed
by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five
cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases
received steroids and/or immunosuppressant therapy. CONCLUSIONS: The clinical
manifestations and pathological changes are not specific in children with AS,
resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are
only observed in a part of patients. There is a high novel mutation rate of
COL4A5 in the detected AS children.
PMID- 28407816
TI - Automatic identification of variables in epidemiological datasets using logic
regression.
AB - BACKGROUND: For an individual participant data (IPD) meta-analysis, multiple
datasets must be transformed in a consistent format, e.g. using uniform variable
names. When large numbers of datasets have to be processed, this can be a time
consuming and error-prone task. Automated or semi-automated identification of
variables can help to reduce the workload and improve the data quality. For semi
automation high sensitivity in the recognition of matching variables is
particularly important, because it allows creating software which for a target
variable presents a choice of source variables, from which a user can choose the
matching one, with only low risk of having missed a correct source variable.
METHODS: For each variable in a set of target variables, a number of simple rules
were manually created. With logic regression, an optimal Boolean combination of
these rules was searched for every target variable, using a random subset of a
large database of epidemiological and clinical cohort data (construction subset).
In a second subset of this database (validation subset), this optimal combination
rules were validated. RESULTS: In the construction sample, 41 target variables
were allocated on average with a positive predictive value (PPV) of 34%, and a
negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%,
whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in
63% of all variables, in the validation sample in 71% of all variables.
CONCLUSIONS: We demonstrated that the application of logic regression in a
complex data management task in large epidemiological IPD meta-analyses is
feasible. However, the performance of the algorithm is poor, which may require
backup strategies.
PMID- 28407817
TI - Preliminary study of the UL55 gene based on infectious Chinese virulent duck
enteritis virus bacterial artificial chromosome clone.
AB - BACKGROUND: Lethal Duck Enteritis Virus (DEV) infection can cause high morbidity
and mortality of many species of waterfowl within the order Anseriformes.
However, little is known about the function of viral genes including the
conserved UL55 gene among alpha herpes virus due to the obstacles in maintenance
and manipulation of DEV genome in host cells. METHODS: In this paper, we
constructed an infectious bacteria artificial chromosome (BAC) clone of the
lethal clinical isolate duck enteritis virus Chinese virulent strain (DEV CHv) by
inserting a transfer vector containing BAC mini-F sequence and selection marker
EGFP into UL23 gene using homologous recombination. UL55 deletion and its
revertant mutant were generated by two-step RED recombination in E. coli on basis
of rescued recombinant virus. The function of UL55 gene in DEV replication and
its effect on distribution of UL26.5 protein were carried out by growth
characteristics and co-localization analysis. RESULTS: The complete genome of DEV
CHv can be stably maintained in E. coli as a BAC clone and reconstituted again in
DEF cells. The generated UL55 deletion mutant based on DEV CHv-BAC-G displayed
similar growth curves, plaque morphology and virus titer of its parental virus in
infected Duck Embryo Fibroblast (DEF) cells. Immunofluorescence assay indicated
that the loss of UL55 gene do not affect the distribution of UL26.5 protein in
intracellular. These data also suggest infectious BAC clone of DEV CHv will
facilitate the gene function studies of DEV genome. CONCLUSIONS: We have
successfully developed an infectious BAC clone of lethal clinical isolate DEV CHv
for the first time. The generated UL55 gene mutant based on that demonstrated
this platform would be a very useful tool for functional study of DEV genes. We
found the least known DEV UL55 is dispensable for virus replication and UL26.5
distribution, and it could be a very promise candidate locus for developing
bivalent vaccine. Experiment are now in progress for testifying the possibility
of UL55 gene locus as an exogenous gene insertion site for developing DEV
vectored vaccine.
PMID- 28407819
TI - [Association between fluid overload and acute renal injury after congenital heart
disease surgery in infants].
AB - OBJECTIVE: To study the association between fluid overload and acute kidney
injury (AKI) after congenital heart disease surgery in infants. METHODS: A
retrospective analysis was performed on 88 infants aged less than 6 months who
underwent a radical surgery for congenital heart disease. The treatment outcomes
were compared between the infants with AKI after surgery and those without. The
effect of cumulative fluid overload on treatment outcomes 2 days after surgery
was analyzed. The risk factors for the development of AKI after surgery were
assessed by logistic regression analysis. RESULTS: Compared with those without
AKI after surgery, the patients with AKI had younger age, lower body weights,
higher serum creatinine levels and higher vasoactive-inotropic score, as well as
longer durations of intraoperative extracorporeal circulation and aortic
occlusion (P<0.05). Compared with those without AKI after surgery, the patients
with AKI had a higher transfusion volume, a higher incidence rate of low cardiac
output syndrome, a longer duration of mechanical ventilation, a longer length of
stay in the intensive care unit (ICU), a longer length of hospital stay, a higher
application rate of extracorporeal membrane oxygenation, a higher 30-day
mortality rate, and higher levels of cumulative fluid overload 2 and 3 days after
surgery (P<0.05). The logistic regression analysis showed that fluid overload and
low cardiac output syndrome were major risk factors for the development of AKI
after surgery. The children with cumulative fluid overload >5% at 2 days after
surgery had a higher incidence rate of low cardiac output syndrome, a longer
duration of mechanical ventilation, a longer length of stay in the ICU, a longer
length of hospital stay, and a higher mortality rate (P<0.05). CONCLUSIONS:
Infants with fluid overload after surgery for congenital heart disease tend to
develop AKI, and fluid overload may be associated with poor outcomes after
surgery.
PMID- 28407820
TI - [Clinical features of hereditary distal renal tubular acidosis and SLC4A1 gene
mutation].
AB - OBJECTIVE: To study the clinical features of two families with distal renal
tubular acidosis (dRTA) and mutations in the pathogenic gene SLC4A1. METHODS:
Family investigation, medical history collection, and measurement of biochemical
parameters were performed to analyze the clinical phenotype and genetic
characteristics of dRTA. Direct sequencing was used to detect SLC4A1 gene
mutations. RESULTS: Three patients in these two families (two of them were mother
and son) were diagnosed with dRTA with typical clinical features, including short
stature, metabolic acidosis, alkaline urine, hypokalemia, and nephrocalcinosis.
SLC4A1 gene analysis showed that all the three patients had a pathogenic missense
mutation R589H (c.1766G>A). The child in family 1 had a de novo mutation of
SLC4A1, and the child in family 2 had an SLC4A1 gene mutation inherited from the
mother, which met the characteristic of autosomal dominant inheritance.
CONCLUSIONS: This study reports the R589H mutation in SLC4A1 gene in families
with hereditary dRTA for the first time in China. Clinical physicians should
perform gene detection for patients suspected of hereditary dRTA to improve the
diagnosis and treatment of this disease.
PMID- 28407821
TI - [Association between platelet-activating factor acetylhydrolase gene
polymorphisms and gastrointestinal bleeding in children with Henoch-Schonlein
purpura].
AB - OBJECTIVE: To study the association between the single nucleotide polymorphisms
(SNPs) of the ninth exon Val279Phe of platelet-activating factor acetylhydrolase
(PAF-AH) gene and gastrointestinal bleeding in children with Henoch-Schonlein
purpura (HSP). METHODS: A total 516 children with HSP were enrolled, among whom
182 had gastrointestinal bleeding and 334 had no gastrointestinal bleeding. PCR
was used to investigate the distribution of genotypes and alleles in the SNPs of
Val97Phe. The plasma PAF-AH activity was measured, as well as the levels of
platelet-activating factor (PAF), granular membrane protein-140 (GMP-140), beta
thromboglobulin (beta-TG), and platelet factor 4 (PF4). RESULTS: The Val279Phe
genotype and allele frequencies were in Hardy-Weinberg equilibrium, and the
homozygous genotype TT and heterozygotes accounted for 0.97% and 6.05%
respectively. The gastrointestinal bleeding group had a significantly higher
allele frequency than the control group (5.22% vs 3.33%; P<0.01). The HSP
patients with GG genotype in the gastrointestinal bleeding group had
significantly higher levels of plasma PAF and GMP-140 than those in the non
gastrointestinal bleeding group (P<0.05), while the non-gastrointestinal bleeding
group had a significantly higher PAF-AH activity than the gastrointestinal
bleeding group (P<0.05). There were no significant differences in beta-TG and PF4
between the two groups (P>0.05). CONCLUSIONS: Val279Phe gene polymorphisms in PAF
AH are associated with PAF-AH activity and PAF and GMP-140 levels and may be a
risk factor for HSP with gastrointestinal bleeding.
PMID- 28407822
TI - [A preliminary study of renal function in small-for-gestational-age infants at
early stage after birth].
AB - OBJECTIVE: To investigate the renal function of small-for-gestational-age (SGA)
infants at the early stage after birth. METHODS: A total of 40 preterm SGA
infants, 33 full-term SGA infants, 80 preterm appropriate-for-gestational-age
(AGA) infants, and 33 full-term AGA infants were included in this study. The
following indices were compared between the SGA infants and AGA infants within 48
hours after admission: blood urea nitrogen (BUN), serum creatinine (SCr),
estimated glomerular filtration rate (eGFR), blood pressure, urine volume per
body weight, and proteinuria. RESULTS: The preterm SGA group had a significantly
lower BUN level than the preterm AGA group (P<0.05). However, there were no
significant differences in SCr level, eGFR, and blood pressure between the two
groups (P>0.05). The full-term SGA group had a significantly higher SCr level and
a significantly lower eGFR than the full-term AGA group (P<0.05). However, there
were no significant differences in BUN level and blood pressure between the two
groups (P>0.05). There was no significant difference in urine volume per body
weight between the preterm SGA and preterm AGA groups (P>0.05) and between the
full-term SGA and full-term AGA groups (P>0.05). There was no significant
difference in the incidence of proteinuria between the preterm SGA and preterm
AGA groups (P>0.05). Proteinuria was not present in the SGA full-term and AGA
full-term groups. CONCLUSIONS: SCr and eGFR can be used as the diagnostic indices
for early renal damage of SGA infants. The renal function is worse in full-term
SGA infants than in full-term AGA infants.
PMID- 28407823
TI - [Application of humidified high-flow nasal cannula in neonates with meconium
aspiration syndrome and pulmonary hypertension after extubation].
AB - OBJECTIVE: To investigate the clinical value of humidified high-flow nasal
cannula (HHFNC) as a respiratory support after extubation by comparing it with
nasal continuous positive airway pressure (NCPAP) in neonates with meconium
aspiration syndrome (MAS) and persistent pulmonary hypertension of the newborn
(PPHN). METHODS: A total of 78 neonates with MAS and PPHN were randomly
administered with HHFNC or NCPAP immediately after extubation. The following
indices were compared between the two groups: blood gas parameters, duration of
noninvasive ventilation, rate of extubation failure, and incidence of
complications, such as nasal damage, abdominal distension, and intraventricular
hemorrhage. RESULTS: There were no significant differences in the rate of
extubation failure, PaO2, PCO2, and PaO2/FiO2 ratio at one hour after NCPAP or
HHFNC, duration of noninvasive ventilation, time to full enteral feeding, length
of hospital stay, and incidence of intraventricular hemorrhage between the two
groups (P>0.05). The HHFNC group had significantly lower incidence of nasal
damage (5.0% vs 31.6%; P<0.05) and incidence of abdominal distension (7.5% vs
34.2%; P<0.05) than the NCPAP group. CONCLUSIONS: Both NCPAP and HHFNC can be
used as the sequential therapy for neonates with MSA and PPHN after extubation,
and they both have a definite effect. As a new strategy of respiratory support,
HHFNC is better tolerated, and has fewer side effects than NCPAP.
PMID- 28407824
TI - [Association between high-mobility group box 1 and neonatal respiratory distress
syndrome].
AB - OBJECTIVE: To study the association between serum level of high-mobility group
box 1(HMGB1) and neonatal respiratory distress syndrome (NRDS). METHODS: A total
of 35 infants with NRDS and 35 normal neonates (control group) were enrolled.
Peripheral venous blood samples were collected with 12-24 hours after birth.
ELISA was used to measure the serum level of HMGB1. RESULTS: The infants with
mild and severe NRDS had a significantly higher serum level of HMGB1 than the
control group (P<0.05). The infants with severe NRDS had a significantly higher
serum level of HMGB1 than those with mild NRDS (P<0.05). The infants with NRDS
who died had a significantly higher serum level of HMGB1 than those who survived
(P<0.05). The receiver operating characteristic (ROC) curve showed that the
optimal cut-off value for serum level of HMGB1 to predict NRDS was 625.3 pg/mL
with an area under the ROC curve (AUC) of 0.846 (95%CI: 0.755-0.936), and the
optimal cut-off value for serum level of HMGB1 to predict the death of infants
with NRDS was 772.2 pg/mL with an AUC of 0.916 (95%CI: 0.813-1.000). CONCLUSIONS:
Infants with NRDS have a significant increase in the serum level of HMGB1, and
the serum level of HMGB1 can well predict the development and prognosis of NRDS.
PMID- 28407825
TI - [Effect of pregnancy-induced hypertension syndrome on complications in very low
birth weight preterm infants].
AB - OBJECTIVE: To study the effect of pregnancy-induced hypertension syndrome (PIH)
on complications in very low birth weight (VLBW) preterm infants. METHODS: The
VLBW preterm infants were enrolled as research subjects, and according to the
presence or absence of PIH in their mothers, they were divided into PIH group and
non- PIH group. The incidence of major complications and length of hospital stay
were compared between the two groups. RESULTS: There were no significant
differences between the two groups in gestational age, birth weight, sex,
incidence rate of maternal diabetes, and use of antepartum hormone. The PIH group
had a significantly higher rate of birth of small-for-gestational-age infants
than the non-PIH group. The PIH group had a significantly lower incidence rate of
bronchopulmonary dysplasia (BPD) than the non-PIH group, while there were no
significant differences between the two groups in the incidence rates of apnea of
prematurity, necrotizing enterocolitis, retinopathy of prematurity, and
intraventricular hemorrhage-periventricular leukomalacia, and the length of
hospital stay. There was no significant difference in the incidence rate of
neonatal respiratory distress syndrome between the two groups, but the PIH group
had a significantly lower proportion of infants who used pulmonary surfactant
than the non-PIH group. CONCLUSIONS: PIH can alleviate respiratory complications
and reduce the use of pulmonary surfactant and the incidence rate of BPD in
preterm infants.
PMID- 28407826
TI - [A retrospective analysis of 6 children with Duchenne muscular dystrophy].
AB - OBJECTIVE: To analyze the clinical features of 6 children with Duchenne muscular
dystrophy (DMD) and review related literature, and to provide a basis for early
diagnosis and effective treatment of this disease. METHODS: A retrospective
analysis was performed on the clinical data of 6 children with DMD who were
admitted to the First Affiliated Hospital of Nanjing Medical University from
January 2010 to October 2015. RESULTS: All the 6 cases were boys without a family
history of DMD, and the age of diagnosis of DMD was 1.2-11.5 years. All patients
had insidious onset and increases in alanine aminotransferase, aspartate
aminotransferase, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase,
creatine kinase (CK), and creatine kinase-MB, particularly CK, which was 3.3
107.2 times the normal level. Their gene detection results all showed DMD gene
mutation. The gene detection results of two children's mothers showed that they
carried the same mutant gene. The muscle biopsy in one case showed that the
pathological changes confirmed the diagnosis of DMD. The level of CK in one case
declined by 77.0% 5 days after umbilical cord blood mesenchymal stem cell
transplantation. CONCLUSIONS: For boys with abnormal serum enzyme levels and
motor function, DMD should be highly suspected. It should be confirmed by CK and
DMD gene detection as soon as possible. And the progression of the disease could
be delayed by early intervention for protecting the remaining normal muscle
fibers.
PMID- 28407827
TI - [Values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in
predicting sensitivity to intravenous immunoglobulin in Kawasaki disease].
AB - OBJECTIVE: To study the values of neutrophil-lymphocyte ratio (NLR) and platelet
lymphocyte ratio (PLR) in predicting the sensitivity to intravenous
immunoglobulin (IVIG) in Kawasaki disease (KD). METHODS: A retrospective cohort
study was conducted in 404 children with newly diagnosed KD. The data on routine
blood tests, NLR, and PLR were collected before and after IVIG treatment. The
receiver operating characteristic (ROC) curve was used to determine the cut-off
values of NLR and PLR in predicting the insensitivity to IVIG. A logistic
regression analysis was used to identify independent predictive factors for
insensitivity to IVIG. RESULTS: Of all patients, 31 were insensitive to IVIG.
Compared with the IVIG sensitivity group, the IVIG insensitivity group had a
significantly higher incidence rate of coronary artery ectasia (P<0.01), a
shorter course of disease when IVIG therapy was initiated (P<0.05), and
significantly higher NLR, PLR, and C-reactive protein (CRP) level before and
after treatment (P<0.05). The optimal cut-off values for NLR and PLR to predict
IVIG insensitivity were 4.36 and 162 before IVIG treatment and 1.45 and 196 after
treatment. The multivariate regression analysis showed that the course of disease
before IVIG treatment, CRP before IVIG treatment, and NLR and PLR before and
after IVIG treatment were independent predictive factors for IVIG insensitivity.
CONCLUSIONS: NLR and PLR can be used to predict IVIG insensitivity in children
with KD.
PMID- 28407828
TI - [Clinical features of invasive candidiasis and risk factors for Candida
bloodstream infection in children: a multicenter study in Urumqi, China].
AB - OBJECTIVE: To investigate the clinical features of invasive candidiasis in
children and the risk factors for Candida bloodstream infection. METHODS: A
retrospective study was performed on 134 children with invasive candidiasis and
hospitalized in 5 tertiary hospitals in Urumqi, China, between January 2010 and
December 2015. The Candida species distribution was investigated. The clinical
data were compared between the patients with and without Candida bloodstream
infection. The risk factors for Candida bloodstream infection were investigated
using multivariate logistic regression analysis. RESULTS: A total of 134 Candida
strains were isolated from 134 children with invasive candidiasis, and non
albicans Candida (NAC) accounted for 53.0%. The incidence of invasive candidiasis
in the PICU and other pediatric wards were 41.8% and 48.5% respectively. Sixty
eight patients (50.7%) had Candida bloodstream infection, and 45 patients (33.6%)
had Candida urinary tract infection. There were significant differences in age,
rate of use of broad-spectrum antibiotics, and incidence rates of chronic renal
insufficiency, heart failure, urinary catheterization, and NAC infection between
the patients with and without Candida bloodstream infection (P<0.05). The
multivariate logistic regression analysis showed that younger age (1-24 months)
(OR=6.027) and NAC infection (OR=1.020) were the independent risk factors for
Candida bloodstream infection. CONCLUSIONS: The incidence of invasive candidiasis
is similar between the PICU and other pediatric wards. NAC is the most common
species of invasive candidiasis. Candida bloodstream infection is the most common
invasive infection. Younger age (1-24 months) and NAC infection are the risk
factors for Candida bloodstream infection.
PMID- 28407829
TI - [Application of pulmonary function and fractional exhaled nitric oxide tests in
the standardized management of bronchial asthma in children].
AB - OBJECTIVE: To investigate the changes of pulmonary function and fractional
exhaled nitric oxide (FeNO) in the standardized treatment of bronchial asthma in
children. METHODS: A total of 254 children who were newly diagnosed with acute
exacerbation of bronchial asthma were selected as asthma group, and they were
divided into two subgroups: asthma with concurrent rhinitis and asthma without
concurrent rhinitis. All patients received the standardized management and
treatment for one year. The pulmonary function parameters included forced
expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid
expiratory flow (MMEF), and mid-expiratory flow at 25%, 50%, and 75% of vital
capacity (MEF25, MEF50, and MEF75). The FeNO levels were measured before
treatment and at 3, 6, 9, and 12 months after treatment. Another 62 healthy
children were selected as the control group, and the pulmonary function and FeNO
levels were measured only once. RESULTS: During one year of standardized
treatment, FEV1, PEF, MMEF, MEF25, MEF50, and MEF75 gradually increased, and FeNO
levels gradually decreased (P<0.05). Indicators of large airway function, such as
FEV1 and PEF, almost returned to normal after 6 months of treatment; indicators
of small airway function, such as MMEF, MEF25, MEF50, and MEF75 almost returned
to normal after 9 months of treatment; there were no significant differences in
the above indices between the asthma group and the control group after one year
of treatment (P>0.05). However, the asthma group had a significantly higher FeNO
levels than the control group after one year of treatment (P<0.05). The asthmatic
patients with concurrent rhinitis had significantly higher FeNO levels than those
without concurrent rhinitis before treatment and 3 months after treatment
(P<0.05). Before treatment, there was a significant negative correlation between
FeNO levels and pulmonary function parameters (P<0.05). CONCLUSIONS: With the
standardized treatment of bronchial asthma in children, pulmonary function
parameters gradually increase and FeNO levels gradually decrease. The recovery of
large airway function occurs earlier than the recovery of small airway function.
Furthermore, the effect of rhinitis on airway responsiveness should be noted.
PMID- 28407830
TI - [Changes in serum YKL-40 level and humoral immune function and their significance
in children with recurrent pneumonia].
AB - OBJECTIVE: To investigate the changes in serum YKL-40 level and humoral immune
function and their significance in children with recurrent pneumonia. METHODS:
Blood samples were collected from 30 children with recurrent pneumonia (recurrent
pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and
30 healthy children (control group). Serum YKL-40 levels were measured by enzyme
linked immunosorbent assay. The correlation between serum YKL-40 level and
laboratory indices related to humoral immune function was analyzed. The receiver
operating characteristic (ROC) curve was used to analyze the diagnostic value of
serum YKL-40 level for recurrent pneumonia. RESULTS: The recurrent pneumonia
group had a significantly higher serum YKL-40 level than the acute pneumonia and
control groups (P<0.05). The acute pneumonia group had a significantly higher
serum YKL-40 level than the control group (P<0.05). Serum levels of IgG and
complement 4 in the recurrent pneumonia group were significantly lower than in
the acute pneumonia group (P<0.05). Serum YKL-40 level was negatively correlated
with serum IgG level (rs=-0.309, P=0.047) and serum complement 4 level (r=-0.324,
P=0.039). The area under the ROC curve of serum YKL-40 level for diagnosing
recurrent pneumonia was 0.958 (95%CI: 0.921-0.994). CONCLUSIONS: Humoral immune
function is low in children with recurrent pneumonia. Serum YKL-40 may be
involved in the occurrence of recurrent pneumonia and can be used as a reference
index for diagnosing recurrent pneumonia.
PMID- 28407831
TI - [A Meta analysis of the efficacy of high-frequency oscillatory ventilation versus
conventional mechanical ventilation for treating pediatric acute respiratory
distress syndrome].
AB - OBJECTIVE: To systematically assess the clinical efficacy of high-frequency
oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) for
treating pediatric acute respiratory distress syndrome (ARDS). METHODS: Data from
randomized controlled trials comparing HFOV and CMV in the treatment of pediatric
ARDS published before July 2016 were collected from the Cochrane Library, PubMed,
Medline, CNKI, and Wanfang Data. Literature screening, data extraction, and
quality assessment were performed by two independent reviewers according to the
inclusion and exclusion criteria. The selected studies were then subjected to a
Meta analysis using the RevMan 5.3 software. RESULTS: A total of 6 studies
involving 246 patients were included. The results of the Meta analysis showed
that there were no significant differences between the HFOV and CMV groups in the
in-hospital or 30-day mortality rate, incidence of barotrauma, mean ventilation
time, and oxygenation index (P>0.05). However, compared with CMV, HFOV increased
the PaO2/FiO2 ratio by 17%, 24%, and 31% at 24, 48, and 72 hours after treatment
respectively, and improved oxygenation in patients. CONCLUSIONS: Although the
mortality rate is not reduced by HFOV in children with ARDS, this treatment can
result in significant improvement in oxygenation compared with CMV. Further large
sample, multicenter, randomized clinical trials will be required to draw a
definitive conclusion.
PMID- 28407832
TI - [Effect of air pollution on respiratory health in school-aged children in the
main urban area of Chongqing, China].
AB - OBJECTIVE: To investigate the effect of air pollution on respiratory health in
school-aged children in the main urban area of Chongqing, China. METHODS: The
main urban area of Chongqing was divided into polluted area and clean area
according to the air pollution data shown on the Environmental Protection Agency
Website of Chongqing between 2010 and 2015. A cluster sampling method was used to
select 695 third- or fourth-grade children from 2 primary schools in the clean or
polluted area as study subjects, with 313 children from the clean area and 382
children from the polluted area. Pulmonary function was examined for all children
and a standard American epidemiological questionnaire (ATS-DLD-78-C) was used to
investigate the prevalence of respiratory diseases and symptoms. RESULTS:
Compared with the clean area, the polluted area had significantly higher
concentrations of inhalable particles (PM10), fine particulate matter (PM2.5),
and nitric oxide (NOX) (P<0.05). The multivariate logistic regression analysis
was performed after adjustment for confounding factors, and the results showed
that compared with those in the clean area, the children in the polluted area had
significantly higher risks of cough (OR=1.644), cough during cold (OR=1.596),
expectoration during cold (OR=2.196), persistent expectoration (OR=1.802), and
wheezing (OR=2.415). The boys and girls in the clean area had significantly
higher forced vital capacity and forced expiratory volume in one second than
those in the polluted area (P<0.05). CONCLUSIONS: Air pollution in the main urban
area of Chongqing is associated with the increased prevalence of respiratory
symptoms in school-aged children and has certain effect on children's pulmonary
function.
PMID- 28407833
TI - [Clinical features of acute poisoning in hospitalized children: an analysis of
586 cases].
AB - OBJECTIVE: To investigate the clinical features of acute poisoning in
hospitalized children. METHODS: A retrospective analysis was performed on the
clinical data of 586 hospitalized children who were diagnosed with poisoning and
discharged from the Children's Hospital of Chongqing Medical University between
January 2006 and December 2015. RESULTS: The patients included 354 males and 232
females (age: 24 days to 15.8 years). Of the 586 cases, 450 (76.8%) were infants
and preschool children; 463 (79.0%) came from rural areas; 551 (94.0%) were
hospitalized because of unintentional poisoning. The drug poisoning, pesticide
poisoning, and rodenticide poisoning accounted for 221 cases (37.7%), 167 cases
(28.5%), and 175 cases (29.9%) respectively. There was a significant difference
in the distribution of the poisoning toxins between urban and rural children
(P<0.01), and drugs and pesticides were the most common toxins for urban and
rural children respectively. There were significant differences in main clinical
manifestations between the children with drug poisoning, pesticide poisoning, and
rodenticide poisoning (P<0.01), who presented with main clinical symptoms of the
nervous system, digestive system, and circulatory system respectively. There was
no significant difference in overall response rate between the children poisoned
by different toxins. CONCLUSIONS: Acute poisoning is most common in infants and
preschool children. The majority of the patients are from rural areas. The
majority of acute poisoning is unintentional. Poisoning by drugs is the main type
of acute poisoning. There is no significant difference in overall response rate
between the children poisoned by different toxins, but their clinical
manifestations are different.
PMID- 28407834
TI - [Interparental conflict and mental health in children and adolescents: the
mediating effect of self-concept].
AB - OBJECTIVE: To examine the mediating effect of self-concept between interparental
conflict and mental health in children and adolescents. METHODS: A total of 689
students (10-18 years) were surveyed using the convenient sampling method, and
their mental health, self-concept, and interparental conflict were examined by
the general status questionnaire, Strengths and Difficulties Questionnaire, Self
Description Questionnaire, and Children's Perception of Interparental Conflict
Scale. Structural equation modeling (SEM) and simultaneous analysis of several
groups were used to construct the mediator model and analyze the data,
respectively. The Bootstrap method was used to assess the significance of the
mediating effects. RESULTS: Interparental conflict was positively correlated with
mental health of children and adolescents (P<0.05), but was negatively correlated
with self-concept (P<0.01). Self-concept was negatively correlated with mental
health (P<0.01). Self-concept had a partial (60%) mediating effect between
interparental conflict and mental health. Academic stage, but not gender, had a
regulatory role on interparental conflict, mental health, and self-concept.
CONCLUSIONS: Self-concept plays an important role between interparental conflict
and mental health. It is necessary to improve self-concept level in children and
adolescents exposed to interparental conflict.
PMID- 28407836
TI - [Role of c-Jun N-terminal kinase-mediated FOXO3a nuclear translocation in
neuronal apoptosis in neonatal rats with hypoxic-ischemic brain damage].
AB - OBJECTIVE: To explore the mechanisms of neuroprotective effects of c-Jun N
terminal kinase (JNK)/FOXO3a transcription factor signaling pathway inhibition on
hypoxic-ischemic neuronal apoptosis in neonatal rats with hypoxic-ischemic brain
damage (HIBD). METHODS: Sixty-four 7-day-old Sprague-Dawley rats were divided
into four groups: hypoxia-ischemia (HI), sham-operated, JNK specific inhibitor
AS601245-treated, and DMSO vehicle. Rats' cerebral cortexes were collected at 24
hours after HI. Western blot was used to detect the protein expression of JNK, p
JNK, FOXO3a, nuclear and cytoplasmic FOXO3a, Bim, and CC3. TUNEL staining was
used to detect the apoptotic cells. RESULTS: Compared with the sham-operated
group, p-JNK protein increased (P<0.01), nuclear protein of FOXO3a increased
(P<0.01), cytoplasmic protein decreased (P<0.01), and pro-apoptotic proteins Bim
and CC3 increased 24 hours after HI (P<0.01). Compared with the HI and DMSO
vehicle groups, p-JNK protein was reduced (P<0.01), nuclear protein of FOXO3a was
also reduced (P<0.01), cytoplasmic protein increased (P<0.01), and Bim and CC3
proteins decreased (P<0.01) in the AS601245-treated group 24 hours after HI.
TUNEL positive cells were reduced in the AS601245-treated rats compared with the
HI and DMSO vehicle groups 24 hours after HI (P<0.01). CONCLUSIONS: JNK activity
increases in the neonatal rat brain with HI damage. JNK activity inhibition can
inhibit FOXO3a translocation from cytoplasm to nucleus and downregulate the
levels of pro-apoptotic proteins Bim and CC3, leading to the reduction of
neuronal apoptosis.
PMID- 28407835
TI - [Recurrent pulmonary infection and oral mucosal ulcer].
AB - An 8-year-old girl who had experienced intermittent cough and fever over a 3 year
period, was admitted after experiencing a recurrence for one month. One year ago
the patient experienced a recurrent oral mucosal ulcer. Physical examination
showed vitiligo in the skin of the upper right back. Routine blood tests and
immune function tests performed in other hospitals had shown normal results.
Multiple lung CT scans showed pulmonary infection. The patient had recurrent
fever and cough and persistent presence of some lesions after anti-infective
therapy. The antitubercular therapy was ineffective. Routine blood tests after
admission showed agranulocytosis. Gene detection was performed and she was
diagnosed with dyskeratosis congenita caused by homozygous mutation in RTEL1.
Patients with dyskeratosis congenita with RTEL1 gene mutation tend to develop
pulmonary complications. Since RTEL1 gene sequence is highly variable with many
mutation sites and patterns and can be inherited via autosomal dominant or
recessive inheritance, this disease often has various clinical manifestations,
which may lead to missed diagnosis or misdiagnosis. For children with unexplained
recurrent pulmonary infection, examinations of the oral cavity, skin, and nails
and toes should be taken and routine blood tests should be performed to exclude
dyskeratosis congenita. There are no specific therapies for dyskeratosis
congenita at present, and when bone marrow failure and pulmonary failure occur,
hematopoietic stem cell transplantation and lung transplantation are the only
therapies. Androgen and its derivatives are effective in some patients. Drugs
targeting the telomere may be promising for patients with dyskeratosis congenita.
PMID- 28407837
TI - [Effects of embryonic lead exposure on food intake and bowel movement in
offspring rats and possible mechanisms].
AB - OBJECTIVE: To study the effects of embryonic lead exposure on food intake and
bowel movement in offspring rats and possible mechanisms. METHODS: Sprague-Dawley
rats were given 0.1% (low-dose lead exposure group) or 0.2% (high-dose lead
exposure group) lead acetate freely during pregnancy to establish an animal model
of embryonic lead exposure. A blank control group was also established. The male
offspring rats were enrolled in the study, and 10 male offspring rats from each
group were selected to observe the changes in food intake, bowel movement,
gastric emptying, intestine propulsion, and pathological inflammatory response in
the gastric mucosa. Eight offspring rats were selected from each group, and
electron microscopy and immunohistochemistry were used to observe the changes in
the ultrastructure of jejunal microvilli and cell junction and the expression of
cholecystokinin-8 (CCK-8) and motilin (MTL) in the feeding center, in order to
reveal the possible mechanisms for abnormal gastrointestinal motility in
offspring rats induced by embryonic lead exposure. RESULTS: Compared with the
control group, the low- and high-dose lead exposure groups had a significant
reduction in daily food intake, a significant increase in water content of feces,
a significant reduction in fecal pellet weight, and a significant increase in
small intestine propulsion (P<0.05). The high-dose lead exposure group had a
significant reduction in gastric emptying ability compared with the control group
(P<0.05). Compared with the control group, the lead exposure groups had
significantly greater pathological inflammatory changes in the gastric mucosa
(P<0.05), significant reductions in the number and length of the jejunal
microvilli and the number of epithelial desmosome junctions (P<0.05), a
significant increase in the macula densa gap (P<0.05), and significant increases
in the expression of MTL and CCK-8 in the feeding center (P<0.05), in a dose
dependent manner. CONCLUSIONS: The degree of gastrointestinal structural injury
and expression levels of MTL and CCK-8 in the feeding center are lead dose
dependent, which may be important mechanisms for changes in food intake, bowel
movement, and digestive functions in offspring rats induced by embryonic lead
exposure.
PMID- 28407838
TI - [Effects of maternal folate deficiency on the methylation of insulin-like growth
factor system in the offspring rats].
AB - OBJECTIVE: To study the effects of maternal folate deficiency on fetal growth and
development and the methylation profiles of insulin-like growth factor system in
the offspring rats. METHODS: Twenty-two Sprague-Dawley female rats were randomly
assigned to two groups: a folate deficient group (n=12) and a control group
(n=10). They were fed with folate deficient and normal diet respectively. Dams
were mated after 2 weeks of feeding. Eight female rats from each group were
pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean
section. Thirty-two fetal rats from each group were randomly selected and the
body length and weight were measured. Eight fetal rats from each group were
randomly selected and ELISA was used to measure the level of folate content, IGF
1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were
randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq)
was used to detect the methylation level of insulin-like growth factor system in
the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP
3 in the maternal serum from both groups. RESULTS: The mean fetal length and
weight were lower in the folate deficient group than in the control group
(P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as
folate content and IGFBP-3 in the fetal brain and liver were significantly lower
in the folate deficient group than in the control group (P<0.05). The methylation
levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal
brain were higher in the folate deficient group than in the control group
(P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the
fetal liver were higher in the folate deficient group than in the control group.
The methylation of IGF-2 gene showed a significant reduction in the folate
deficient group (P<0.05). CONCLUSIONS: Maternal folate deficiency may cause
retardation of growth and development of the offspring, which is possibly
associated with the changes of methylation profiles of insulin-like growth
factors.
PMID- 28407839
TI - [Effect of histone acetylation/deacetylation imbalances on key gene of planar
cell polarity pathway].
AB - OBJECTIVE: To investigate the effect of histone acetylation/deacetylation
imbalances on embryonic hearts of mice and its effect on key genes of planar cell
polarity (PCP) pathway-Vangl2, Scrib and Rac1 in H9C2 cells. METHODS: Forty
pregnant C57/B6 mice were randomly assigned into three groups: blank group
(n=10), vehicle group (n=10), and valproic acid (VPA)-treated group (n=20). In
the VPA-treated group, VPA, a histone deacetylase (HDAC) inhibitor, was
administered to each individual dam intraperitoneally at a single dose of 700
mg/kg on embryonic day 10.5 (E10.5). The vehicle and blank groups received
equivalent saline or no interventions, respectively. Dams were sacrificed on
E15.5, and death rates of embryos were evaluated. Subsequently, embryonic hearts
of survival fetus were removed to observe cardiac abnormalities by hematoxylin
eosin (HE) staining. H9C2 cells were cultured and allotted to the blank, vehicle,
and VPA-treated groups: the VPA treated group received VPA exposure at
concentrations of 2.0, 4.0 and 8.0 mmol/L; the vehicle and blank groups received
equivalent saline or no interventions, respectively. HDAC1-3 as well as Vangl2,
Scrib and Rac1 mRNA and protein expression levels were determined by quantitative
real-time PCR and Western blot, respectively. The total HDAC activity was
analyzed by colorimetric assay. RESULTS: The fetus mortality rate after VPA
treatment was 31.7%, with a significantly higher rate of cardiac abnormalities in
comparison with the controls (P<0.05). In comparison with the blank and vehicle
groups, HDAC1 mRNA was significantly increased at various concentrations of VPA
treatment at all time points of exposure (P<0.05), together with a reduction of
protein level after 48 and 72 hours of exposure (P<0.05). The inhibition of HDAC2
mRNA after various concentrations of VPA incubation was pronounced at 24 hours of
exposure (P<0.05), while the protein levels were reduced at all time points
(P<0.05). HDAC3 mRNA was prominently induced by VPA (4.0 and 8.0 mmol/L) at all
time points of treatment (P<0.05). In contrast, the protein level was inhibited
after VPA treatment (P<0.05). In comparison with the blank and vehicle groups,
Vangl2 mRNA as well as Scrib mRNA/protein expression levels were markedly reduced
after 48 and 72 hours of VPA treatment (P<0.05), together with a reduction of
protein level in Vangl2 at 72 hours (P<0.05). Compared with the blank and vehicle
groups, a significant repression in the total HDAC activity was observed in the
VPA-treated group at concentrations of 4.0 and 8.0 mmol/L after 24 hours of
treatment (P<0.05), and the effect persisted up to 48 and 72 hours, exhibiting
pronounced inhibition at all concentrations (P<0.05). CONCLUSIONS: VPA might
result in acetylation/deacetylation imbalances by inhibiting HDAC1-3 protein
expression and total HDAC activity, leading to the down-regulation of mRNA and
protein expression of Vangl2 and Scrib. This could be one of the mechanisms
contributing to congenital heart disease.
PMID- 28407840
TI - [Advances in research on childhood neutropenia].
AB - Neutrophils, an important type of human immune cells, are involved in host
defense against infections. Neutropenia refers to a group of diseases manifesting
as a reduction in the absolute value of mature neutrophils and is often
accompanied by an increased risk of bacterial infection. According to etiology
and pathogenesis, neutropenia is classified into congenital and acquired
neutropenia. This article reviews the current research status and advances in the
etiology of neutropenia in children. A deep understanding of the etiology of
neutropenia helps to improve the diagnosis and treatment of this disease.
PMID- 28407841
TI - Cardiovascular Comorbidity in Inflammatory Rheumatological Conditions.
AB - BACKGROUND: Approximately 1.5 million adults in Germany suffer from an
inflammatory rheumatological condition. The most common among these are
rheumatoid arthritis and spondyloarthritis-above all axial spondyloarthritis,
including ankylosing spondylitis (Bekhterev's disease) and psoriatic arthritis.
These systemic inflammatory diseases often affect the heart as well. METHODS:
This review is based on pertinent articles retrieved by a selective literature
search, on current European guidelines, and on the authors' clinical experience.
RESULTS: Rheumatic inflammation of cardiac structures can manifest itself as
pericarditis, myocarditis, or endocarditis. The heart valves and the intracardiac
conduction system can be affected as well, leading to AV block. Functional
sequelae, e.g., congestive heart failure, can arise as a consequence of any
inflammatory rheumatic disease. The long-term mortality of rheumatic diseases is
elevated predominantly because of the increased risk for cardiovascular
comorbidities. The cardiovascular risk profile should therefore be re-evaluated
regularly (e.g., at 5-year intervals) in cooperation with the patient's primary
care physician. The cardiovascular manifestations of rheumatic disease, such as
pericarditis, myocarditis, and vasculitis, are treated initially with high-dose
glucocorticoids and then over the long term with maintenance drugs such as
methotrexate and azathioprine. Biological agents are sometimes used as well.
CONCLUSION: In patients with inflammatory rheumatic diseases, the elevated
cardiovascular risk should be kept in mind and preventive measures should be
initiated early. This subject should be further studied in controlled trials so
that the treatment options for patients with cardiac involvement can be
evaluated.
PMID- 28407843
TI - Questionable Validity of Data Sources.
PMID- 28407842
TI - The Prevalence of Glaucoma in Young People.
AB - BACKGROUND: Earlier information on the prevalence of glaucoma among children in
Germany was based solely on estimates. Reported values for congenital glaucoma
range from 1 in 10 000 to 1 in 68 000 depending on ethnic origin. The estimate
for juvenile glaucoma is 1 in 44 000. METHODS: The Gutenberg Health Study is a
populationbased, prospective, monocentric cohort study with 15 010 participants
aged 35 to 74. To determine the history-based prevalence of childhood glaucoma,
participants were asked about the diagnosis of glaucoma, any operations for
glaucoma that were performed, regular use of drugs for glaucoma, and the age of
onset of glaucoma. The affected individuals were classified in four groups based
on the age of onset: congenital (<2 years), juvenile (2 to <18 years), late
juvenile (18 to <40 years), and early adult (40 to <45 years). In the identified
glaucoma patients, the visual acuity, intraocular pressure, corneal thickness,
visual fields, and optic discs were evaluated. RESULTS: 352 persons were
identified from their medical history as having glaucoma. The weighted
prevalences in the four groups were 0% in the congenital group, 0.01% (95%
confidence interval [0, 0.03]) in the juvenile group, 0.16 % ([0.09; 0.23]) in
the late juvenile group, and 0.17% ([0.15; 0.19]) in the early adult group. For
participants over age 45, the weighted prevalence of glaucoma was 1.98% [1.7;
2.2]. CONCLUSION: In our cohort, the history-based prevalence of juvenile
glaucoma was 0.01% (2 patients). The prevalence was an order of magnitude higher
(0.16%) between the ages of 18 and 40, and two orders of magnitude higher at
later ages (1.98%). The burden of disease seems to be markedly higher than
previously assumed.
PMID- 28407844
TI - In Reply.
PMID- 28407845
TI - New Perspectives for the Importance of Cardiometabolic Risk Factors.
PMID- 28407846
TI - In Reply.
PMID- 28407847
TI - Emphasis on Dual Antithrombotic Therapy.
PMID- 28407848
TI - Prescriptions Are the Remit of the Doctor.
PMID- 28407849
TI - In Reply.
PMID- 28407850
TI - Association between subclinical hypocalcemia in the first 3 days of lactation and
reproductive performance of dairy cows.
AB - The objective of this study was to determine the effects of subclinical
hypocalcemia on reproductive performance in dairy cows. In a prospective cohort
study, 97 cows on 2 dairy farms with automatic milking systems were monitored for
subclinical hypocalcemia. Animals were enrolled 7 +/- 3 days prior to estimated
calving date and three parity groups were defined based on the lactation that the
animals were going to start: lactation = 1, lactation = 2, and lactation >=3.
Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM
and subclinical hypocalcemia (SCH) was defined as Ca <= 8.6 mg/dL; animals that
presented a low Ca level during all 3 days were classified as chronic SCH (cSCH).
Return to cyclicity during the voluntary waiting period was analyzed based on
weekly progesterone concentrations measured in serum. Information on reproductive
outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were
collected from on-farm software after all study cows had completed their study
period. Chronic SCH was present in all parity groups with higher incidence in
multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity >= 3
animals). The cSCH animals took longer to show active ovaries when compared to
eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model
animals with normal Ca were 1.8 times more likely to return to cyclicity by the
end of the voluntary waiting period when compared to cSCH animals. Animals with
cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic
cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia
had a negative effect on return of ovarian function during the voluntary waiting
period and decreased the odds of pregnancy at first service. Those cows with cSCH
had an even more pronounced impaired reproductive function than those with one
subclinical measurement.
PMID- 28407851
TI - Time-dependent changes and prognostic value of lactatemia during the first 24 h
of life in brachycephalic newborn dogs.
AB - Blood lactate concentration is known to be a good prognostic indicator associated
with the severity of illness and the patient's outcome both in human and
veterinary medicine. It also plays a significant role in the assessment of the
newborn, being a good indicator of fetal hypoxia and the ideal predictor of
morbidity at term in babies. In veterinary neonatal medicine, hyperlactatemia is
considered a valid prognostic marker in critically ill foals; moreover, blood
lactate measurement has been proposed for the evaluation of newborn viability and
the assessment of fetal distress during delivery in dogs. Unfortunately, only a
few studies have been published concerning the canine species. The present work
examines 67 brachycephalic newborn dogs and their mothers, with the aim to
evaluate the time-dependent changes of blood lactate and glucose concentration
during the first 24 h after vaginal or caesarean delivery both in puppies and
bitches. To our knowledge, this is the first published study examining the time
dependent changes of these parameters in the bitch after parturition. Within the
studied population of puppies, non-surviving was significantly associated with a
higher lactatemia and a lower APGAR score. Blood lactate was high at birth then
progressively decreased during the first 24 h of life and a lack of normalization
of blood lactate levels within this time interval was suggestive for a poor
prognosis for the newborn dogs; moreover, the decrease appeared to be slower
after vaginal delivery. Lactatemia also showed a positive correlation with
glycemia at birth. Concerning the bitches examined, blood lactate was found to be
significantly higher after vaginal delivery than after caesarean section; the
normalization occurred within 24 h after parturition. Blood glucose level was
significantly higher at 2 h from delivery both in the group of bitches submitted
to caesarean section and in those undergoing natural whelping but no statistical
correlation was found between maternal glycemia and lactatemia. The results of
the present study highlighted that the monitoring of lactatemia during the first
24 h of life, in association with the assessment of the APGAR score at birth, can
be an useful prognostic tool helping to identify the most severely distressed
puppies and to provide them an adequate support.
PMID- 28407852
TI - Establishment and characterization of a telomerase immortalized porcine luteal
cells.
AB - Luteal cells play a crucial role in pregnancy through secreting progesterone to
maintain pregnancy and support of fetus. However, low cellular yields and
inability to passage primary porcine luteal cells (PLCs) in vitro limit the
luteal cell study. Therefore, developing an immortalized porcine luteal cell line
is necessary for studying luteal cells activity and function in different
diseases. In this study, primary PLCs were obtained from gilts at day 30 to day
50 of gestation and immortalized by human telomerase reverse transcriptase
(hTERT). The porcine corpus luteal cell line (hTERT-PLCs) expressed hTERT gene
steady, maintained high hTERT activity and normal karyotype. The phase contrast
microscope and transmission electron microscope observation showed primary PLCs
and hTERT-PLCs were polygonal and exhibited abundant mitochondria, smooth
endoplasmic reticulum and lipid droplets. 3beta hydroxysteroid dehydrogenase
(3betaHSD) and Oil-Red-O staining showed that hTERT-PLCs at passage 30 and 50
were similar to primary PLCs. The hTERT-PLCs expressed steroidogenesis-related
proteins, enzymes and receptors, such as steroidogenic acute regulatory protein,
P450 cholesterol side-chain cleavage, 3betaHSD, 20alphaHSD, luteinizing hormone
receptor, progesterone receptor, prolactin receptor, estrogen receptoralpha/beta,
as well as primary PLCs. Consequently, hTERT-PLCs could secret progesterone and
exhibited similar responses to luteinizing hormone and prostaglandin F2alpha as
primary PLCs. In addition, the hTERT-PLCs did not show neoplastic transformation
or anchorage independent growth. In summary, we developed an immortalized porcine
luteal cell line which maintained its originally morphological, biological and
functional characteristics.
PMID- 28407853
TI - Effects of environmental enrichment on reproductive performance and quantity and
morphology of cumulus-oocyte complexes obtained from Rattus norvegicus.
AB - Several researchers have observed that environmental enrichment (EE) can be
effective in reducing stressful conditions and abnormal behavior and may provide
better reproductive performance in rodents. In this context, this study aimed to
evaluate the reproductive performance of Wistar rats reared in three different
housing conditions. Animals were separated into breeding pairs, one pair per cage
and pairs randomly assigned to three experimental groups (ten couples per group):
control group were provided cages without any environmental enrichment; PVC group
with PVC pipe; and cardboard roll group with a commercially available cardboard
tube. To compare the reproductive performance of the three groups, the following
were evaluated: number of pups/litter; number of litters; parturition interval;
occurrence of cannibalism; weight gain of offspring; as well as the quantity and
quality of cumulus-oocyte complexes (COCs) obtained after superovulation of the
females born from the first, second and last pregnancy in all groups. Moreover,
the plasma level of corticosterone in breeding animals was measured. A total of
60 male rats randomly selected from the first- and last-born litters (20 males
from each group) were first tested in an elevated plus-maze (EPM) and on the
following day, were tested in an open field test (OFT). Significant differences
were found in the number and morphological classification of COCs. In the control
group, the number of oocytes in grade 4 (unusual shapes and very heterogeneous
ooplasm, presenting no layers of surrounding cumulus cells [13]) presented
statistically higher rates (225/2535, 8.9%) compared to the other groups, as well
as the number of competent oocytes was higher in the enriched groups (p = 0.001).
Moreover, we find that the males of cardboard roll group differed significantly
in weight gain compared to PVC group (p = 0.008). In addition to this, we did not
detect occurrence of cannibalism in this group. Our findings suggest that
environmental enrichment provides improvements in reproductive performance of
Wistar rats.
PMID- 28407854
TI - Corrigendum to ''Failure of a single dose of medroxyprogesterone acetate to
induce uterine infertility in postnatally treated domestic cats'' [Theriogenology
85(4) (2016) 718-723].
PMID- 28407855
TI - Corrigendum to "Reducing treatments in cattle superovulation protocols by
combining a pituitary extract with a 5% hyaluronan solution: Is it able to
diminish activation of the hypothalamic pituitary adrenal axis compared to the
traditional protocol?" [Theriogenology 85 (2016) 914-921].
PMID- 28407856
TI - Relationship between circulating progesterone at timed-AI and fertility in dairy
cows subjected to GnRH-based protocols.
AB - The objectives of this retrospective study were: 1) to investigate the effect of
plasma progesterone (P4) concentrations at the time of timed-AI (TAI) on
fertility, and 2) to examine risk factors associated with plasma P4
concentrations that impair fertility in lactating dairy cows subjected to GnRH
based protocols. Data from 872 lactating Holstein cows that had, or had not been
presynchronized prior to a 7-day GnRH-based TAI protocol were examined. However,
data from only those cows (n = 697; 79.9%) that ovulated after second GnRH were
analyzed. Plasma P4 concentrations were determined using a solid-phase
radioimmunoassay. Transrectal ultrasonography was used to determine cyclicity at
first GnRH treatment, ovulation after first and second GnRH treatments, and
pregnancy status at 32 and 60 d after TAI. Parity, days in milk (DIM) and BCS
were also recorded. Plasma P4 concentrations at TAI ranged from 0.0 to 9.94 ng/mL
(overall mean +/- SEM, 0.32 +/- 0.02 ng/mL) and 41 (5.9%) cows had P4 >= 1.0
ng/mL at TAI. The percentage of cows diagnosed pregnant at 32 and 60 d after TAI
was 45.1 and 41.6%, respectively, and pregnancy loss from 32 to 60 d after TAI
was 7.6%. Plasma P4 concentrations at TAI affected (P < 0.01) P/AI at 32 and 60
d, but did not affect (P > 0.1) pregnancy loss. No cows with plasma P4
concentrations >0.80 ng/mL became pregnant. However, ROC curve analysis revealed
that the optimal P4 threshold at TAI for P/AI at 32 d was <=0.50 ng/mL, with a
sensitivity and specificity of 94.9 and 20.9, respectively. The percentage of
cows with plasma P4 concentrations >0.50 ng/mL was 15.8% (110/697). Furthermore,
a significant (P < 0.05) quadratic relationship between plasma P4 concentrations
at TAI and P/AI at 32 d was observed. The maximum predicted probability of
pregnancy was 0.54 at a P4 concentration of 0.26 ng/mL. Based on the odds ratios
(OR), cows with P4 <= 6.2 ng/mL at PGF were 2.3 times less likely to have P4 >
0.50 ng/mL at TAI compared to cows with P4 > 6.2 ng/mL (OR = 0.44; 95% CI = 0.27
to 0.71; P < 0.01). Also, cyclic cows subjected to presynchronization were less
likely to undergo luteal regression than non-presynchronized or acyclic cows (OR
= 5.3; 95% CI = 1.77 to 16.27; P < 0.01). In summary, plasma P4 concentrations
>0.50 ng/mL at TAI resulted in significantly reduced fertility. As elevated
plasma P4 concentrations at TAI were more frequent in cows with lower P4 at PGF
or those subjected to presynchronization, both groups are most likely to benefit
from an additional PGF treatment prior to TAI.
PMID- 28407857
TI - A review of the ongoing discussion about definition, diagnosis and pathomechanism
of subclinical endometritis in dairy cows.
AB - In the last decade, several new aspects of the inflammation of the bovine
endometrium have been investigated and described, including a new definition of
subclinical endometritis. This review summarizes the recent discussion about the
definition, diagnosis and pathomechanism of subclinical endometritis. Subclinical
endometritis also referred to as cytological endometritis is defined by findings
of endometrial cytology, which is usually performed with the cytobrush-technique
or by low-volume flushing of the uterus. The sampling procedure is minimally
invasive and has no negative impact on subsequent conception rate. The suggested
threshold value for polymorphonuclear cells (PMN) as diagnostic for subclinical
endometritis depends on the time postpartum and varies from 5 to 18%. It has also
been shown that a general threshold of 5% PMN is eligible for all cows between 21
and 62 days postpartum. Accuracy and repeatability of counting PMN under the
microscope have been evaluated and can be regarded as reliable. The impact of
subclinical endometritis on reproductive performance is characterized by
decreased conception rates, and prolonged days to first service and days open. In
addition, it has been demonstrated that subclinical endometritis has an impact on
survival and quality of the embryo. Some studies, however, did not confirm this
negative effect of subclinical endometritis on fertility. More detailed analyses
of the cytobrush samples revealed higher mRNA expression of several cytokines in
cows with subclinical endometritis compared with healthy cows, and contributed to
the understanding of detrimental effects of subclinical endometritis on
fertility. In contrast to clinical endometritis, there are no predominant
bacteria related to subclinical endometritis, but associations between the
presence of alpha-hemolytic streptococci and Trueperella pyogenes and subclinical
endometritis have been found. For the treatment of subclinical endometritis,
intrauterine infusions with cephapirin as well as the administration of PGF2alpha
have been recommended. Other studies, however, did not confirm the efficiency of
these treatments.
PMID- 28407858
TI - Influence of lipoproteins at dry-off on metabolism of dairy cows during
transition period and on postpartum reproductive outcomes.
AB - High-yielding dairy cows are metabolically challenged during transition, when
intense mobilization and hepatic oxidation of lipids is achieved, thus leading to
fatty infiltration, ketosis and generalized inflammation. The condition is
associated to periparturient diseases and poor fertility. The aim of this study
was to assess whether serum lipoprotein concentrations in the dry period could
influence the occurrence of postpartum diseases and reproductive performance in
dairy cows. The study was carried out on 30 multiparous Holstein Friesian cows.
Blood samples were collected at dry-off (-60 days), 30 days after dry-off and
within 12 h after parturition for biochemical and serum lipoprotein assays. From
10 to 60 days after parturition milk was collected twice weekly after feeding,
for milk whey progesterone assay. The Optimal Cutpoint package identified a
threshold of 89% for serum High Density Lipoprotein (HDL) concentration at the
beginning of the dry period with 95% of confidence interval. Cows with serum HDL
greater than 89% (High group, n = 10) showed better reproductive performance when
compared to those with low values (Low group, n = 18). The odds ratio for
reproductive disorders in High group was 0.6875, however, differences were not
significant probably due to both the reduced number of animals per group and
overall low incidence of postpartum reproductive disease. First postpartum luteal
activity occurred around day 23, while the second one between days 40 and 48. The
average calving to first AI interval was 64.00 +/- 3.95 days and 94.50 +/- 12.32
days in High and Low group, respectively (P < 0.05). The calving-conception
interval was 129.86 +/- 24.42 days and 199.18 +/- 24.73 days in High and Low
groups, respectively (P < 0.05). Low group displayed an increase in liver
markers, that is total bilirubin, with 0.46 +/- 0.09 mg/dL and 0.23 +/- 0.08
mg/dL, in Low and High group respectively (P < 0.05), and NEFA/cholesterol ratio,
with 0.30 +/- 0.06 and 0.14 +/- 0.03, in Low and High groups, respectively (P <
0.05), at parturition. Concentrations of HDL >89% at dry-off could be suggestive
of improved liver adaptation to the transition, and probably of enhanced
fertility in High group.
PMID- 28407859
TI - Establishment of intraperitoneal germ cell transplantation for critically
endangered Chinese sturgeon Acipenser sinensis.
AB - Recent progress in germ cell transplantation techniques in fish has paved the way
for the conservation of endangered species. Here, we developed an intraperitoneal
germ cell transplantation procedure using Chinese and Dabry's sturgeon as donor
and recipient species, respectively. Histological analysis revealed that
primordial germ cells migrated on the peritoneal wall at 16 days post-hatch (dph)
in Dabry's sturgeon. The genital ridges of Dabry's sturgeon (recipient) first
formed at 28 dph, suggesting that for successful colonization of donor germ cells
in the recipient gonads, the transplantation should be performed earlier than
this age. Sexual dimorphism of gonadal structure was first observed at 78 dph.
Gonadal germ cell proliferation was not seen in either sex during this period.
Immunohistochemistry using the anti-Vasa antibody found that donor testes from 2
year-old Dabry's sturgeon mainly consisted of single- or paired-type A
spermatogonia, while donor ovaries from 11.5-year-old Chinese sturgeon had
perinucleolus stage oocytes and clusters of oogonia. Donor cells isolated from
Dabry's sturgeon testes or Chinese sturgeon ovary labeled with PKH26 fluorescent
dye were transplanted into the peritoneal cavity of the 7- or 8-dph Dabry's
sturgeon larvae. More than 90% and 70% of transplanted larvae survived after 2
days post-transplantation (dpt) and 51 dpt, respectively. At 51 dpt, PKH26
labeled cells exhibiting germ cell-specific nuclear morphology and diameter were
observed in excised recipient gonads by fluorescent and confocal microscopy. The
colonization rate of allogeneic testicular germ cell transplantation (Group 1)
was 70%, while that of two batches of xenogeneic ovarian germ cell
transplantation (Group 2 and Group 3) were 6.7% and 40%, respectively. The ratio
of colonized germ cells to endogenous germ cells was 11.96%, 5.35% and 3.56% for
Group 1, Group 2 and Group 3, respectively. Thus, we established a germ cell
transplantation technique for the critically endangered Chinese sturgeon using
the most closely related species as a recipient and demonstrated the successful
preparation of transplantable female germ cells from aged adult Chinese sturgeon.
PMID- 28407860
TI - Effects of MG132 on the in vitro development and epigenetic modification of Debao
porcine somatic cell nuclear transfer embryos.
AB - The present study was undertaken to examine the effect of MG132, a proteasome
inhibitor, on the in vitro development, zygotic genome activation (ZGA) and
epigenetic modification of Debao porcine somatic cell nuclear transfer (SCNT)
embryos. Treatment of oocytes with 1 MUM MG132 from 30 h to 42 h of maturation
and SCNT embryos with 5 MUM MG132 for 2 h after fusion resulted in higher
blastocyst yield (36.5%) of SCNT embryos compared with the control group (11.0%).
The ZGA of SCNT embryos at 2- and 4-cell stages was also enhanced by MG132
treatment through altering the RNA pol II status and increasing the expression of
eIF3A and TFIIA. Meanwhile, MG132 treatment also resulted in increase of inner
cell mass (ICM) and trophectoderm (TE) and total cell numbers and decrease of
apoptotic cell numbers of SCNT blastocysts. Expression of BCL-2, OCT4, NANOG and
CDX2 in SCNT blastocysts developed from SCNT embryos and oocytes treated with
MG132 was increased significantly (P < 0.01), while the expression of pro
apoptotic BAX gene was suppressed significantly (P < 0.01). In addition, MG132
treatment not only affected the expression patterns of H3K9 acetylation, H3K4 and
H3K9 trimethylation, but also regulated the relative expression of SMYD3, ASH2L,
KDM5B, HAT1, HDAC1 and HDAC2 of Debao porcine SCNT embryos. These results
demonstrate that MG132 treatment can improve the developmental potential of Debao
porcine SCNT embryos through regulating the expression of genes related to
histone acetylation and the processes of ZGA.
PMID- 28407861
TI - Influence of different types of lamps on the reproductive development of male
Japanese quail (Coturnix coturnix japonica).
AB - Reproductive tract development during puberty is critical to reproductive
performance, and the light is crucial in this process in birds. However, in male
quail, there is little information on the effects of types of lamps, more
specifically the wavelength emitted. Thus, the objective was to evaluate the
effects of types of lamps on the reproductive performance of male Japanese quail
(Coturnix coturnix japonica). Two hundred and forty male quail were exposed to
six different types of lamp (incandescent, white fluorescent, or blue, white, red
or green LED). The experimental design was completely randomized with six
treatments and five replicates of one quail. Quail were slaughtered on days 35,
47, 57, 71 and 123 to evaluate the development of testes. On day 117, semen
samples were analyzed and fertilized eggs were incubated. Body weight of the
quails was influenced (P < 0.01) by lamps only until the 47 days of age. Higher
body weight until this age were observed with incandescent, blue and green LED
bulbs. Fluorescent and red LED bulbs propitiated (P < 0.05) early testicular
development of quails but, at 57 days of age, higher testicular development was
obtained (P < 0.01) whit white LED bulbs. Lower testicular development was
observed (P < 0.01) at 123 days of age with the red LED. No influence of
different types of lamps was observed (P > 0.05) on the quality of semen nor on
the fertility rates of quail. It is concluded that lamps can influence the
histological reproductive characteristics of male quails, but without influencing
the semen quality. Fluorescent bulbs and red LED seem to anticipate the sexual
maturity, but the white LED results in higher testicular development at 57 days
of age.
PMID- 28407862
TI - Lipid profiles of follicular fluid from cows submitted to ovarian
superstimulation.
AB - Ovarian superstimulation with exogenous gonadotropins has been extensively used
to produce in vivo-derived embryos for embryo transfer in cattle. This process
modifies the antral follicle microenvironment and affects oocyte and embryo
quality as well the differentiation of granulosa cells. Lipids play significant
roles in the cell, such as energy storage, cell structure, and fine-tuning of the
physical properties and functions of biological membranes. The phospholipid (PL)
contents as well as the effects of superstimulatory treatments on the PL profile
of follicular fluid from cows, however, remain unknown. Therefore, to gain
insight into the effects of superstimulation with follicle-stimulating hormone
(FSH; P-36 protocol) or FSH combined with equine chorionic gonadotropin (eCG; P
36/eCG protocol) on the profile and abundance of PL from cows submitted or not
submitted to superstimulatory protocols, were treated with these two
superstimulatory protocols. As a control, non-superstimulated cows were only
submitted to estrous synchronization. The follicular fluid was aspirated, the
remaining cells removed and the follicular fluid stored at -80 degrees C until
extraction. The lipid screening was performed by matrix-assisted laser desorption
ionization mass spectrometry (MALDI-MS) and this technique allowed the
identification of sphingomyelins (SM) and phosphatidylcholines (PC) and
phosphoethanolamines (PE). The relative abundance of the ions observed in the
three experimental groups was analyzed by multivariate and univariate statistical
models. The phospholipid SM (16:0) and PC (36:4) and/or PC (34:1) were less (P <
0.05) abundant in the P-36 group compared to the control or P-36/eCG groups.
However, the PC (34:2) was more (P < 0.05) abundant in both group of
superstimulated cows compared to the control. In summary, ovarian
superstimulation seems to modulate the PL content of bovine follicular fluid with
a significant increase in PC (34:2), which jointly with others PC and SM, seems
to offer a suitable biomarker involved with reproductive processes successful as
ovary superstimulation response and embryo development.
PMID- 28407863
TI - Reproductive characteristics of female white-tailed deer (Odocoileus virginianus)
in the Midwestern USA.
AB - Knowledge of reproductive characteristics of wild populations is necessary to
inform responsible management decisions that promote herd health. As management,
goals, and free-ranging populations change over time and landscapes, updated
knowledge of reproductive characteristics are needed to inform responsible
management practices. We estimated reproductive characteristics of female white
tailed deer in Illinois, including pregnancy rate, litter size, fetal growth and
fetal sex ratio. We found maternal age to have an important influence on several
reproductive factors. Approximately 66% of tested females (n = 3884) were
pregnant and pregnancy rates increased with increasing maternal age, from 20.5%
in fawns to 85.8% in adult deer. Litter size ranged from 1 to 5 fetuses per
pregnant female. The average litter size was 1.9 +/- 0.54 fetuses per pregnant
female and also increased with age, from 1.2 in fawns to 2.0 in adults,
respectively. Breeding season peaked in November with the mean estimated
conception dates of fetuses varying with maternal age. Fawns conceived fetuses
later in the breeding season (December 2) compared to yearlings and adults
(November 11 and 8, respectively). We measured the body mass index (BMI) of all
fetuses and found that litter size and female age influence fetal size. We found
no bias in fetal sex ratio (average 1.0:1.0, male:female) but we observed a sex
bias in fetal size (mean BMI male = 0.71, female 0.67) across all maternal age
classes. A comparison of the current study and previous reports indicate that
variation in maternal age within a population is an important driver of
reproductive metrics, likely because maternal age and body size or condition are
related. Furthermore, variation in resource availability will influence
reproductive rates, especially among fawn females.
PMID- 28407864
TI - Birth of cloned mice from vaginal smear cells after somatic cell nuclear
transfer.
AB - Less invasive methods for donor cell collection will facilitate reproduction of
wild animals using somatic-cell nuclear transfer. Stages of the estrous cycle in
mice have long been studies using somatic cells that can be collected from
vaginal walls using cotton tipped swabs in a relatively non-invasive manner. In
this study, we examined the feasibility of these cells as sources of nuclei for
somatic-cell cloning using nuclear transfer. Estrous cycles generally comprise
proestrus, estrus, metestrus, and diestrus stages. In the present experiments,
more than 60% of cells were nucleated in vaginal smears from all but the estrus
stage. However, after somatic-cell nuclear transfer of cells from proestrus,
metestrus, and diestrus stages, 66%, 50%, and 72% of cloned embryos developed to
the morula/blastocyst, and cloned female mouse birth rates after embryo transfer
were 1.5%, 0.3%, and 1%, respectively. These results show that noninvasively
collected vaginal smears contain somatic cells that can be used to clone female
mice.
PMID- 28407865
TI - The effect of dual-hemisphere breeding on stallion fertility.
AB - Breeding records were analyzed from 24 Thoroughbred stallions that were subjected
to dual-hemisphere breeding (DH), including novice (first-year; NOV; n = 11) and
experienced (EXP; n = 13) stallions. Fertility variables included seasonal
pregnancy rate, pregnancy rate per cycle, and first-cycle pregnancy rate. In
addition, values for book size, total number of covers, distribution of mare type
(maiden, foaling, and barren) within a stallion's book, cycles per mare, and mare
age were examined. Some data were also categorized by mare type (maiden-M,
foaling-F, and barren-B). Five separate analyses of the data were performed. For
Analyses 1-3, the effects of hemisphere (northern hemisphere [NH] vs. southern
hemisphere [SH]) and breeding order (refers to the first [O1] or second [O2]
season within the first year of dual-hemisphere breeding) were examined for all
stallions (combined group [CG]), NOV stallions only, and EXP stallions only,
respectively. Fertility values were generally higher in the SH than the NH (P <
0.05), whereas book size, total number of covers, and cycles per mare were higher
in the NH than the SH (P < 0.05). Book size and total covers were negatively
correlated to first cycle pregnancy rate (r = -0.57, r = -0.71, respectively; P <
0.05) for NOV stallions. Pregnancy rate per cycle was also negatively correlated
with total covers (r = -0.58; P < 0.05) for NOV stallions. Similar trends were
noted for Groups CG and EXP, but the relationship was not as marked as for NOV
stallions. The fertility of O1 was generally similar to O2 (P > 0.05). For
Analysis 4, fertility of DH breeding seasons was compared to single hemisphere
(SIN) breeding seasons within the same 16 stallions and was found to be similar
between the two groups (P > 0.05). For Analysis 5, the effect of the number of
consecutive DH breeding seasons on fertility was examined and was found to remain
unchanged (P > 0.05). In summary, no adverse effects of DH breeding on fertility
were detected. Fertility was higher when stallions were bred in the SH, as
compared to the NH. Potential reasons for higher fertility achieved in the SH
were smaller book sizes and better mare reproductive quality.
PMID- 28407866
TI - Subclinical endometritis in beef cattle in early and late postpartum: Cytology,
bacteriology, haptoglobin and test strip efficiency to evaluate the evolution of
the disease.
AB - In cows, detrimental effects on fertility are mainly caused by clinical and
subclinical endometritis (SEM). As demonstrated in previous work, Piedmontese
cattle are affected by a higher rate of infertility and presence of SEM. The
objective of this study is to assess the pattern of SEM at 30 and 60 days
postpartum by evaluating the correlation between uterine cytology and
microbiology, analyzing SEM consequences on reproductive career and verifying the
reliability of rising inflammatory proteins - haptoglobin and the test strip
test. Seventy healthy cows were enrolled and sampled at 30 and 60 days
postpartum; cytology and bacteriology as well as haptoglobin and test strip were
evaluated. The ROC curve for cytology set the optimal cut-off at 6.5% at 30 days
and 2.5% at 60 days for a Partum-to-Conception (PC) interval of 120 days. The
cytological positivity was negatively correlated with fertility, at 30 days, but
not at 60 days. A positive bacteriological test was not correlated with an
increase in the PC at either 30 or 60 days postpartum. The presence of a calving
parlor affect the fertility (P < 0.05) but not the presence of parity or suckling
calf and parity. The ROC curve for strip test protein at 30 days postpartum set a
cut-off of 2% for PC. No difference in serum haptoglobin was observed between
negative or positive cytology/bacteriology in postpartum cattle. The test strip
results for proteins have demonstrated a utility at 30 days postpartum for
screening the cows that are at risk of developing an increased PC > 120 days.
PMID- 28407868
TI - [New European guidelines for cardiovascular prevention and its Spanish
adaptation].
PMID- 28407867
TI - The relationship between mitochondrial DNA copy number and stallion sperm
function.
AB - Mitochondrial DNA (mtDNA) copy number has been utilized as a measure of sperm
quality in several species including mice, dogs, and humans, and has been
suggested as a potential biomarker of fertility in stallion sperm. The results of
the present study extend this recent discovery using sperm samples from American
Quarter Horse stallions of varying age. By determining copy number of three
mitochondrial genes, cytochrome b (CYTB), NADH dehydrogenase 1 (ND1) and NADH
dehydrogenase 4 (ND4), instead of a single gene, we demonstrate an improved
understanding of mtDNA fate in stallion sperm mitochondria following
spermatogenesis. Sperm samples from 37 stallions ranging from 3 to 24 years old
were collected at four breeding ranches in north and central Texas during the
2015 breeding season. Samples were analyzed for sperm motion characteristics,
nuclear DNA denaturability and mtDNA copy number. Mitochondrial DNA content in
individual sperm was determined by real-time qPCR and normalized with a single
copy nuclear gene, Beta actin. Exploratory correlation analysis revealed that
total motility was negatively correlated with CYTB copy number and sperm
chromatin structure. Stallion age did not have a significant effect on copy
number for any of the genes. Copy number differences existed between the three
genes with CYTB having the greatest number of copies (20.6 +/- 1.2 copies, range:
6.0 to 41.1) followed by ND4 (15.5 +/- 0.8 copies, range: 6.7 to 27.8) and
finally ND1 (12.0 +/- 1.0 copies, range: 0.4 to 26.6) (P < 0.05). Varying copy
number across mitochondrial genes is likely to be a result of mtDNA fragmentation
and degradation since downregulation of sperm mtDNA occurs during spermatogenesis
and may be important for normal sperm function. Beta regression analysis
suggested that for every unit increase in mtDNA copy number of CYTB, there was a
4% decrease in the odds of sperm movement (P = 0.001). Influential analysis
suggested that results are robust and not highly influenced by data from
individual stallions despite the low number of stallions sampled with low sperm
motility. Further genome sequencing is necessary to investigate if mutations or
deletions are the underlying causes of inconsistent copy numbers across
mitochondrial genes. In conclusion, we show, for the first time, that increased
mtDNA copy number is associated with decreased total sperm motility in stallions.
We therefore suggest that mtDNA copy number may be an indicator of defective
spermatogenesis in stallions.
PMID- 28407869
TI - [Brexit and community health professionals].
PMID- 28407870
TI - Edematous Dermatomyositis with Probable Evans Syndrome.
PMID- 28407872
TI - Further investigation of distinct components of Stroop interference and of their
reduction by short response-stimulus intervals.
AB - The aim of this paper is to extend the so-called semantic Stroop paradigm (Neely
& Kahan, 2001) - which already successfully distinguishes between the
contribution of the semantic vs. response conflict to Stroop interference - so
that it can take account of and capture the separate contribution of task
conflict. In line with this idea, the Stroop interference observed using the
aforementioned paradigm with both short and long RSIs (500 vs. 2000ms) did indeed
reflect the specific contribution of the task, semantic and response conflicts.
However, the contribution of task conflict (as opposed to the semantic and
response conflicts) failed to reach significance when the semantic Stroop
paradigm was administered with manual (Experiment 1) as opposed to vocal
responses (Experiment 2). These experiments further tested the extent to which
the specific contribution of the different conflicts can be influenced by the
increased cognitive control induced by a short (vs. long) RSI. The corresponding
empirical evidence runs contrary to the assumption that the reduction of overall
Stroop interference by a short (vs. long) RSI is due to the reduced contribution
of the task (Parris, 2014) and/or semantic (De Jong, Berendsen, & Cools, 1999)
conflicts. Indeed, in neither experiment was the contribution of these conflicts
reduced by a short RSI. In both experiments, this manipulation only reduced the
contribution of the response conflict to the overall Stroop interference (e.g.,
Augustinova & Ferrand, 2014b). Thus these different results clearly indicate that
Stroop interference is a composite phenomenon involving both automatic and
controlled processes. The somewhat obvious conclusion of this paper is that these
processes are more successfully integrated within multi-stage accounts than
within the historically favored single-stage response competition accounts that
still dominate current psychological research and practice.
PMID- 28407871
TI - Acral Hemorrhagic Darier Disease.
AB - Darier disease is an autosomal-dominant inherited condition caused by mutation of
a gene, which produces a protein involved in calcium channel regulation. The
disease has a variety of manifestations and lacks consistent genotype-phenotype
correlations. Acral hemorrhagic Darier disease causes macules, papules, vesicles
and/or hemorrhagic blisters on the extremities. Other classic signs of the
disease may be present in the same patient or relatives. Histopathology reveals
dyskeratosis and suprabasal acantholysis with hemorrhagic lacunae. We report 3
new cases of this type of Darier disease triggered by injuries. Response to
retinoid therapy was good.
PMID- 28407874
TI - Autophagy and renal epithelial transport: eat to survive.
AB - Autophagy is an adaptive cellular response to "stress" in which proteins are
targeted for lysosomal degradation. Using a combined proteomics and microscopy
approach, Khositseth et al. show that autophagy contributes to the downregulation
of the water channel aquaporin-2 in response to hypercalcemia. This commentary
discusses the role of autophagy in renal epithelial transport, and explores
whether autophagy may also contribute to chronic kidney disease once it becomes
dysfunctional.
PMID- 28407873
TI - The spleen as a bidirectional signal transducer in acute kidney injury.
AB - In acute kidney injury models, the lung is damaged through an interleukin-6
dependent inflammatory response. Clinically, development of lung injury requiring
mechanical ventilation markedly increases in-hospital acute kidney injury
mortality. Andres-Hernando et al. demonstrate that the spleen coordinates
interleukin-6-dependent interleukin-10 production, which lessens lung injury
during experimental acute kidney injury. This study highlights the beneficial
influence of the spleen on the lung, and dovetails with other recent
publications, to demonstrate the integral role of the spleen in acute kidney
injury.
PMID- 28407875
TI - Mendelian randomization to establish the causality of uric acid with diabetic
nephropathy in type 1 diabetics.
AB - Previous studies have demonstrated an association of serum uric acid with kidney
disease. However, it is unknown whether this relationship is causal. Mendelian
randomization takes advantage of allele randomization at birth to assess
causation. Using this technique Ahola et al. found strong evidence against
causation in Finnish Caucasians with type 1 diabetes mellitus. However,
replication in other populations is needed to further assess a potential causal
role for hyperuricemia in kidney disease.
PMID- 28407876
TI - More frequent hemodialysis does not effectively clear protein-bound azotemic
solutes derived from gut microbiome metabolism.
AB - The 5-year survival rate for hemodialysis patients remains lower than that for
some of the more common solid organ cancers. Trials of increasing urea clearance
by hemodialysis have failed to demonstrate improved patient survival.
Accumulating evidence suggests that protein-bound azotemic solutes derived from
gut microbiome metabolism have greater potential for toxicity than urea. The
Frequent Hemodialysis Network Trials group now report that increasing dialysis
frequency to 6 times a week did not effectively improve clearance of these
protein-bound azotemic solutes compared with standard thrice weekly sessions.
PMID- 28407877
TI - Simultaneous liver-kidney transplantation: shifting renal allograft gene
expression from inflammation toward preservation.
AB - Exposure of renal allografts to donor-specific antibodies activates many
proinflammatory genes, resulting in antibody-mediated rejection. Simultaneous
liver transplantation reduces the development of antibody-mediated rejection in
renal grafts exposed to donor-specific antibodies. A study by Taner et al. in
this issue of Kidney International shows this effect of the liver to involve more
than simply absorbing donor-specific antibodies, with a shift in the pattern of
gene expression in the kidney away from proinflammatory toward preservation of
tissue function.
PMID- 28407878
TI - The Authors Reply.
PMID- 28407880
TI - Oellgaard J, Gaede P, Rossing P, et al. Intensified multifactorial intervention
in type 2 diabetics with microalbuminuria leads to long-term renal benefits.
Kidney Int. 2017;91:982-988.
PMID- 28407879
TI - Regarding "Obesity increases the risk of end-stage renal disease among living
kidney donors".
PMID- 28407881
TI - Enlarged seminal vesicles as an initial presentation of polycystic kidney
disease.
PMID- 28407882
TI - Tunneled dialysis catheters might receive "permanent resident" status after a
while: a case for caution.
PMID- 28407883
TI - The Case | Hypomagnesemia with knee pain.
PMID- 28407885
TI - The sweetest thing: blocking fructose metabolism to prevent acute kidney injury?
AB - Fructose consumption has been linked to hypertension in animal models and human
studies, and endogenous fructose metabolism has been shown to promote acute and
chronic kidney injury in mice. A recent study published in Nature Communications
demonstrates a reduction in ischemic acute kidney injury with genetic knockout or
inhibition of fructokinase, which catalyzes the first step in fructose
metabolism. Although the role of this pathway in human kidney disease remains
unclear, the recent description of several candidate fructokinase inhibitors may
allow for clinical studies in the future.
PMID- 28407886
TI - Incidence and Prognostic Impact of Heart Failure Hospitalization During Follow-Up
After Primary Percutaneous Coronary Intervention in ST-Segment Elevation
Myocardial Infarction.
AB - The incidence of heart failure (HF) hospitalization and its impact on long-term
outcomes have not been well evaluated in contemporary patients with ST-segment
elevation myocardial infarction (STEMI) after primary percutaneous coronary
intervention (PCI). The Coronary Revascularization Demonstrating Outcome Study in
Kyoto Acute Myocardial Infarction (AMI) Registry is a multicenter registry
enrolling 5,429 consecutive patients with AMI undergoing PCI from 2005 to 2007.
The present study population consisted of 3,682 patients with STEMI who underwent
primary PCI within 24 hours of symptom onset and discharged alive. The incidence
of HF hospitalization was 4.4%/year during the first year after the index STEMI,
which attenuated to approximately 1.0%/year beyond 1 year to 5 years with the
median follow-up period of 1,956 days. The independent risk factors for HF
hospitalization within 1 year included older age, previous myocardial infarction,
HF at STEMI, left ventricular dysfunction, anterior AMI, and onset-to-balloon
time >3 hours, use of beta blocker, and nonuse of statin at discharge. By the
landmark analysis at 1 year, the cumulative incidences of all-cause death and HF
hospitalization beyond 1 year and up to 5 years were significantly higher in
patients with HF hospitalization within 1 year of STEMI than in patients without
(36.3% vs 10.1%, p <0.001, and 40.4% vs 4.3%, p <0.001, respectively). Even after
adjusting for confounders, HF hospitalization within 1 year remained
independently associated with a higher risk for death and HF hospitalization
beyond 1 year (hazard ratio 1.64, 95% CI 1.02 to 2.52, p = 0.04 and HR 5.72, 95%
CI 3.46 to 9.22, p <0.001, respectively). In conclusion, HF hospitalization
within 1 year was independently associated with a higher risk for all-cause death
and HF hospitalization beyond 1 year.
PMID- 28407887
TI - How to address continued health care differences and disparities among people
with disability.
PMID- 28407888
TI - Erratum to ''The impact of therapeutic massage on adult residents living with
complex and high level disabilities: A brief report'' [Disabil. Health J. 9(4)
(2016):730-734].
PMID- 28407889
TI - Reductive amination derivatization for the quantification of garlic components by
isotope dilution analysis.
AB - In this work, we synthesized internal standards for four garlic organosulfur
compounds (OSCs) by reductive amination with 13C, D2-formaldehyde, and developed
an isotope dilution analysis method to quantitate these organosulfur components
in garlic samples. Internal standards were synthesized for internal absolute
quantification of S-allylcysteine (SAC), S-allylcysteine sulfoxide (alliin), S
methylcysteine (SMC), and S-ethylcysteine (SEC). We used a multiple reaction
monitoring (MRM) to detect 13C, D2-formaldehyde-modified OSCs by ultrahigh
performance liquid phase chromatography coupled with tandem mass spectrometry
(UHPLC-MS/MS) and obtained MS spectra showing different ratios of 13C, D2
formaldehyde-modified and H2-formaldehyde-modified compounds. The resulting
labeled and unlabeled OSCs were exhibited correlation coefficient (R2) ranged
from 0.9989 to 0.9994, respectively. The average recoveries for four OSCs at
three concentration levels ranged from 89% to 105%. By 13C, D2-formaldehyde and
sodium cyanoborohydride, the reductive amination-based method can be utilized to
generate novel internal standard for isotope dilution and to extend the
quantitative application.
PMID- 28407890
TI - Characterization and authentication of Spanish PDO wine vinegars using
multidimensional fluorescence and chemometrics.
AB - This work assesses the potential of multidimensional fluorescence spectroscopy
combined with chemometrics for characterization and authentication of Spanish
Protected Designation of Origin (PDO) wine vinegars. Seventy-nine vinegars of
different categories (aged and sweet) belonging to the Spanish PDOs "Vinagre de
Jerez", "Vinagre de Montilla-Moriles" and "Vinagre de Condado de Huelva", were
analyzed by excitation-emission fluorescence spectroscopy. A visual assessment of
fluorescence landscapes pointed out different trends with vinegar categories.
PARAllel FACtor analysis (PARAFAC) extracted the potential fluorophores and their
values in the PDO vinegars. This information, coupled with different
classification methods (Partial Least Square Discrimination Analysis "PLS-DA" and
Support Vectors Machines "SVM"), was able to discriminate the wine vinegar
category within each PDO, for which SVM models obtained better results (>92% of
classification). In each category, SVM also allows the differentiation between
PDOs. The proposed methodology could be used as an analysis method for the
authentication of Spanish PDO wine vinegars.
PMID- 28407891
TI - Antioxidants and alpha-glucosidase inhibitors from "Liucha" (young leaves and
shoots of Sibiraea laevigata).
AB - The young leaves and shoots of Sibiraea laevigata, known as "Liucha", are used as
tea by Tibetans to improve digestion after meals. Long-term consumption of
"Liucha" will cause weight loss. In present work, we reported on the isolation
and NMR and chemical analysis-based elucidation of seven new sorbitol O-caffeic
acid ester derivatives named sorbitol esters A-G (1-7) and eighteen known
phenolic compounds from S. laevigata. All of the isolates were evaluated for
their antioxidant and alpha-glucosidase inhibitory activities. Among them
sorbitol ester A (1), sorbitol ester D (4), sorbitol ester F (6), sorbitol ester
G (7), isoferulic acid (15), methyl caffeate (18), trans-p-hydroxycinnamic acid
(19), and kaempferol 3-O-beta-d-(6"-E-p-coumaroyl)-glucopyranoside (25) showed
more potent alpha-glucosidase inhibitory activity than the clinical drug
acarbose.
PMID- 28407892
TI - Molecular characterization and bio-functional property determination using SDS
PAGE and RP-HPLC of protein fractions from two Nigella species.
AB - This study aimed to investigate the molecular and bio-functional properties of
protein fractions from Nigella damascena and Nigella arvensis, including the
albumin, globulin, glutein-1, glutein-2 and prolamin fractions. Protein subunits
were not observed in globulin and prolamin fractions. No peaks appeared in RP
HPLC chromatograms of globulin for either species. Two predominant peaks were
observed in the RP-HPLC profiles of all protein fractions. Proteins separated by
RP-HPLC have potential inhibitory and antioxidant activities in all fractions.
Optimum ACE-inhibitory and antioxidant activities of proteins separated by RP
HPLC were observed in glutein-2 and albumin, respectively, for both species. For
pepsin and combined pepsin-trypsin hydrolyses, the highest degree of hydrolysis
(DH) was obtained in glutein-2 fraction of Nigella arvensis. Highest ACE
inhibitory activity of hydrolyzed protein fractions was found at 4h via pepsin
hydrolysis in globulin fraction of Nigella damascena. Highest antioxidant
activities of hydrolyzed protein fractions were found in glutelin-2 for both
species.
PMID- 28407893
TI - H2O2 oxidative preparation, characterization and antiradical activity of a novel
oligosaccharide derived from flaxseed gum.
AB - In this present study, a novel flaxseed gum oligosaccharide (FGOS) was prepared
by H2O2 oxidative degradation method followed by physicochemical properties
characterization and antiradical activity evaluation. Results indicated that the
degradation rate of flaxseed gum is 37.81% under the optimum conditions (i.e.,
reaction temperature of 120 degrees C, H2O2 concentration of 0.2M and reaction
time of 2.0h) and FGOS as a reddish brown semisolid was obtained. Physicochemical
properties identification showed that FGOS has a molecular weight of 1047Da and
is a typical oligosaccharide which contains uronic acid. Characterizations showed
FGOS is acid glycopyranose that consists of rhamnose, fucose, xylose, mannose,
arabinose, glucose and galactose with mole percentages of 8.26%, 7.54%, 12.85%,
7.93%, 29.31%, 14.28% and 19.82% respectively. FGOS exhibited good free radical
scavenging ability (OH 82.58%, DPPH 52.74% and ABTS 91.29% at most,
respectively), suggesting its potent antiradical activity.
PMID- 28407894
TI - Acrylamide and 5-hydroxymethylfurfural formation during biscuit baking. Part II:
Effect of the ratio of reducing sugars and asparagine.
AB - This study investigated acrylamide and 5-hydroxymethylfurfural (HMF) formation
during biscuit baking. Four types of wheat flour with different molar ratios of
total fructose and glucose to asparagine were investigated. Nevertheless, the
molar ratio in all four biscuit doughs exceeded one after proofing due to enzyme
action. Data obtained after baking were used to develop a mechanistic model,
based on the asparagine-related pathway, for acrylamide and HMF formation in the
four baked biscuit types. Asparagine reacted with fructose to form a Schiff base
before decarboxylation to produce acrylamide without Amadori rearrangement
product and sugar fragmentation. Fructose contributed considerably to acrylamide
formation and to HMF formation via caramelization in all four biscuit types. No
clear correlation was found between acrylamide and HMF in baked biscuits, nor
between asparagine and the sum of glucose and fructose concentrations in the
wheat flour.
PMID- 28407895
TI - Test for l-glutamate inhibition of growth of Alternaria alternata by inducing
resistance in tomato fruit.
AB - Although numerous studies have reported the involvement of glutamate in plant
abiotic stress, relatively little is known about the role of glutamate in plant
defence against pathogens. To gain further knowledge, we investigated the effect
of glutamate on Alternaria alternata in tomato fruit. A multidisciplinary
approach was pursued, combining exogenous glutamate applications, enzymatic
activity measurements and real-time quantitative PCR analysis. The results showed
glutamate significantly reduced the disease incidence in tomato caused by A.
alternata, by inducing resistance (Duncan's test, p<0.05). A large variety of
defence-related enzymes and genes involved in the glutamine synthetase/glutamate
synthase cycle, energy-generated metabolism, such as the gamma-aminobutyric acid
shunt, glycolysis and the tricarboxylic acid cycle, and the salicylic acid
signalling pathway were activated by glutamate. The activation of these pathways
as mentioned above might play a potential role in the resistance mechanisms
underpinning glutamate-induced plant immunity.
PMID- 28407896
TI - One-pot synthesis of ethylenediamine-connected graphene/carbon nanotube composite
material for isolation of clenbuterol from pork.
AB - A fluffy porous ethylenediamine-connected graphene/carbon nanotube composite
(EGC), prepared by a simple and time-saving one-pot synthesis, was successfully
applied as an adsorbent in pipette-tip solid-phase extraction (PT-SPE) for the
rapid extraction and determination of clenbuterol (CLB) from pork. In the one-pot
synthesis, carbon nanotubes were inserted into graphene sheets and then connected
with ethylenediamine through chemical modification to form a three-dimensional
framework structure to prevent agglomeration of the graphene sheets. Under the
optimum conditions for extraction and determination, good linearity was achieved
for CLB in the range of 15.0-1000.0ngg-1 (r=0.9998) and the recoveries at three
spiked levels were in the range of 92.2-96.2% with relative standard deviation
<=9.2% (n=3). In comparison with other adsorbents, including silica, NH2, C18,
and Al2O3, EGC showed higher extraction and purification efficiency for CLB from
pork samples. This analytical method combines excellent adsorption performance of
EGC and high extraction efficiency of PT-SPE.
PMID- 28407897
TI - 1H NMR-based compositional identification of different powdered infant formulas.
AB - Infant formulas (IFs), most of which are bovine milk-based, are important for
normal growth and development. However, information regarding the ingredients in
IFs is often limited in detail, and chemical changes during production and
storage appear common. Therefore, it is important to understand in detail the
composition of IFs. In this study, a wide range of low-molecular-weight organic
components in commercial IFs were determined using the 1H nuclear magnetic
resonance (NMR) technique. The components emerging after multivariate data
analysis could be used to discriminate certain infant formulas from each other.
Particular attention was given to the components with potentially beneficial
bioactivities. Our study indicates that NMR spectroscopy in combination with
multivariate data analysis constitutes an efficient tool for the comprehensive
characterization of various IFs and the in-depth understanding of the nutritional
value of IFs for infants.
PMID- 28407898
TI - Convective drying kinetics of strawberry (Fragaria ananassa): Effects on
antioxidant activity, anthocyanins and total phenolic content.
AB - The thermal drying effects on strawberries were investigated in terms of the
kinetics of antioxidant activity (AA), anthocyanins (A) and total phenolic
compound content (TPC), as well as the final colour. The evaluated drying
temperatures were 50 and 60 degrees C with an air rate of 1.5m/s. The 2,2
diphenyl-2-picryl-hydrazyl, pH differential and Folin-Ciocalteu methods were used
to assess the antioxidant properties. The kinetics of TPC and AA showed an
initial and final period of degradation attributed to inhibition of enzymes. A
plateau between these two periods suggests that under certain conditions of
temperature and water content, no degradation reactions occurred. Final losses of
up to 74, 45 and 78% were found for AA, A and TPC, respectively. The total colour
change (DeltaE) was lesser degree at 60 than 50 degrees C. Thermal degradation of
the antioxidant compounds followed a first-order reaction kinetics and the
degradation rate constants (k) were calculated.
PMID- 28407899
TI - In vitro evaluation of whole faba bean and its seed coat as a potential source of
functional food components.
AB - In vitro studies were conducted to evaluate the particular nutritional benefits
of whole faba bean seed (WFB) and fava bean seed coat (FBSC). Total dietary fiber
contents of WFB and FBSC were 27.5% and 82.3%, respectively. FBSC were contained
much higher total phenolic substances, condensed tannins, and total antioxidant
activity than WFB. Bile acid (BA)-binding capacities of in vitro digested samples
and nutritionally important products produced by in vitro fermentation of
digestion residues were also studied. The BA-binding capacities of WFB and FBSC
were 1.94 and 37.50MUmol/100mg, respectively. Total BA bound by FBSC was even
higher than the positive standard cholestyramine. Lignin and other constituents
of the Klason residue were found to influence BA-binding properties. Moreover,
the extent of the in vitro fermentation process showed that, fermentability of
FBSC residue was significantly lower than that of WFB residue. Overall, faba
bean, especially its seed coat, has great potential as a functional food.
PMID- 28407900
TI - Lipophilization and MS characterization of the main anthocyanins purified from
hibiscus flowers.
AB - Hibiscus sabdariffa flowers represent an interesting source of anthocyanins, one
of the most important plant pigments, which are responsible of the intense red
color of the calyces, and have potential as natural colorants for food
applications. Nevertheless, anthocyanins are highly hydrosoluble and unstable
compounds. On this basis, the aim of this work was to increase the lipophilicity
of the hibiscus anthocyanins by lipophilization, in order to obtain amphiphilic
colorants, which could be easily incorporated in lipid-rich food matrices.
Octanoyl derivatives of delphinidin-3-O-sambubioside and cyanidin-3-O
sambubioside were chemically obtained for the first time, and characterized by
means of HPLC-ESI-MS data.
PMID- 28407902
TI - The prediction of food additives in the fruit juice based on electronic nose with
chemometrics.
AB - Food additives are added to products to enhance their taste, and preserve flavor
or appearance. While their use should be restricted to achieve a technological
benefit, the contents of food additives should be also strictly controlled. In
this study, E-nose was applied as an alternative to traditional monitoring
technologies for determining two food additives, namely benzoic acid and
chitosan. For quantitative monitoring, support vector machine (SVM), random
forest (RF), extreme learning machine (ELM) and partial least squares regression
(PLSR) were applied to establish regression models between E-nose signals and the
amount of food additives in fruit juices. The monitoring models based on ELM and
RF reached higher correlation coefficients (R2s) and lower root mean square
errors (RMSEs) than models based on PLSR and SVM. This work indicates that E-nose
combined with RF or ELM can be a cost-effective, easy-to-build and rapid
detection system for food additive monitoring.
PMID- 28407901
TI - Measurement of antioxidant activity with the thiobarbituric acid reactive
substances assay.
AB - The thiobarbituric acid reactive substances (TBARS) assay is widely used to
measure lipid oxidation and antioxidant activity in food and physiological
systems. However, there has been no review (to our knowledge) that focuses
exclusively on this test. This review presents an overview of the current use of
the TBARS test in food and physiological systems, before looking at the various
ways in which the assay is used in studies on antioxidant activity. As an
antioxidant assay, the TBARS test may lack acceptable reproducibility, and long
reaction times may preclude its adoption as a rapid screening method. Despite
these potential limitations, there are features of the TBARS test that make it
useful as a complement to popular screening tests such as Trolox equivalent
antioxidant capacity. This review concludes with proposals for development of the
TBARS test so that it can be used as a rapid and robust antioxidant assay.
PMID- 28407903
TI - Perceived bitterness character of beer in relation to hop variety and the impact
of hop aroma.
AB - The impact of hop variety and hop aroma on perceived beer bitterness intensity
and character was investigated using analytical and sensory methods. Beers made
from malt extract were hopped with 3 distinctive hop varieties (Hersbrucker, East
Kent Goldings, Zeus) to achieve equi-bitter levels. A trained sensory panel
determined the bitterness character profile of each singly-hopped beer using a
novel lexicon. Results showed different bitterness character profiles for each
beer, with hop aroma also found to change the hop variety-derived bitterness
character profiles of the beer. Rank-rating evaluations further showed the
significant effect of hop aroma on selected key bitterness character attributes,
by increasing perceived harsh and lingering bitterness, astringency, and
bitterness intensity via cross-modal flavour interactions. This study advances
understanding of the complexity of beer bitterness perception by demonstrating
that hop variety selection and hop aroma both impact significantly on the
perceived intensity and character of this key sensory attribute.
PMID- 28407904
TI - Characterization and functionalities study of hemicellulose and cellulose
components isolated from sorghum bran, bagasse and biomass.
AB - This study was undertaken to isolate and characterize three carbohydrate-rich
fractions: Hemicellulose A (Hemi. A), Hemicellulose B (Hemi. B) and cellulose
rich residue (CRF) from sorghum bran (SBR), sorghum bagasse (SBA) and sorghum
biomass (SBI). The monosaccharide composition of the Hemi. A and Hemi. B
fractions was determined, indicating that SBR has a highly branched structure.
The analysis of insoluble dietary fiber (IDF), soluble dietary fiber (SDF) and
total dietary fiber (TDF) showed that TDF and IDF contents in original sorghum
materials were in the following order: SBA?SBI?SBR. CRF from SBA was rich in IDF.
Hemi. B fractions were completely soluble in water and so they were rich in SDF.
CRFs from all sorghum sources show high water holding capacity (22.76 to 35.27g
water/g CRF). The emulsion stability study showed that the Hemi. B from all
sorghum sources had a better emulsion stability than the well-studied corn fiber
gum (CFG).
PMID- 28407905
TI - Fate of ethanol during cooking of liquid foods prepared with alcoholic beverages:
Theory and experimental studies.
AB - To obtain an understanding of the ethanol loss during cooking of liquid foods
containing alcoholic beverages, ethanol concentration was measured as a function
of time and remaining volume in meat stocks prepared with wine and beer. A
mathematical model describing the decline in volatile compounds during heating of
simple liquid foods was derived. The experimental results and the model show that
concentration of ethanol at any given time is determined by the initial
concentration and a power law function of the remaining volume fraction. The
power law function is found to be independent of factors like pot dimensions and
temperature. When using a lid to cover the pot during cooking, the model was
still valid but the ethanol concentrations decreased more steeply, corresponding
to a higher exponent. The results provide a theoretical and empirical guideline
for predicting the ethanol concentration in cooked liquid foods.
PMID- 28407906
TI - Antioxidant and antibiofilm activities of secondary metabolites from Ziziphus
jujuba leaves used for infusion preparation.
AB - Ziziphus jujuba Mill., jujube, leaf infusions are popular bedtime beverages as
they improve sleep by soothing the nerves. With the aim of providing further
insights into the polyphenol content of jujube leaf infusion and their
antioxidant activities, a 2,2-diphenyl-1-picrylhydrazyl (DPPH)-guided
purification of the aqueous extract of Z. jujuba Mill. leaves was conducted.
Three major antioxidant polyphenols (i.e. quercitrin, catechin and gallocatechin)
of the leaves were identified. In addition, a significant antibiofilm bioactivity
against Streptococcus mutans, a causative agent of human dental caries, was
detected for the aqueous leaf extract and its bio-guided separation resulted in
the identification of the lupane triterpenoid alphitolic acid as the main
antibiofilm metabolite. The results herein presented further promote the
consumption of jujube leaf infusion as a healthy antioxidant bedtime beverage,
and associate it to an unreported anti-caries activity.
PMID- 28407907
TI - The effects of postharvest application of lecithin to improve storage potential
and quality of fresh goji (Lycium barbarum L.) berries.
AB - To enhance storage life and post-storage quality of fresh goji berries, three
treatments with lecithin (1, 5, 10g.L-1) and two storage times (8, 16days) were
evaluated. The significant effects on the physiological and biochemical
parameters were varied. 1g.L-1 lecithin showed its main effects after 8days of
storage by reduction in total weight loss and decay, SSC/TA ratio (also at
16days), and chlorophyll content and with highest scores of sensory attributes
(also at 16days). 5g.L-1 lecithin showed its main effects after 16days of
storage: highest SSC, highest TA (also at 8days), highest TPC, only significant
reduction in DPPH antioxidant activity, and highest total flavonoid content.
10g.L-1 lecithin showed its main effects after 8days of storage with highest SSC,
chlorophyll content, total flavonoid, DPPH, and ABTS antioxidant activity (also
at 16days), but with least scores of sensory attributes.
PMID- 28407908
TI - Stability of goji bioactives during extrusion cooking process.
AB - Due to the increasing popularity of goji berries, efforts are made to enlarge the
offer of goji containing foods. In this study, rice flour based extrudates
enriched with goji berries were investigated. The extrusion was performed using a
twin screw extruder with constant feed moisture and screw speed. Raw mixtures as
well as extruded products obtained were analysed in order to determine
antioxidant activity and contents of rutin, zeaxanthin dipalmitate and 2-O-beta-d
glucopyranosyl-l-ascorbic acid. The antioxidant activity of goji extrudates was
boosted up to 20times compared to the extrudates without any addition. The
process of extrusion increased the antioxidant activity despite of decrease in
rutin content. Regardless of extrusion conditions rutin retention in the
extrudates was not lower than 60% compared to the respective raw mixtures. In the
case of zeaxanthin dipalmitate the retention level was around 40%. 2-O-beta-d
glucopyranosyl-l-ascorbic acid was stable at the conditions applied.
PMID- 28407909
TI - Effect of temperature and relative humidity on stability following simulated
gastro-intestinal digestion of microcapsules of Bordo grape skin phenolic extract
produced with different carrier agents.
AB - The stability of microparticles of Bordo grape skin aqueous extract, produced by
spray-drying and freeze-drying using polydextrose (5%) and partially hydrolyzed
guar gum (5%), was evaluated under accelerated conditions (75 and 90% relative
humidity, at 35, 45, and 55 degrees C for 35days) and simulated gastrointestinal
digestion. The temperature had a significant effect on the reduction of phenolics
content, with retentions varying from 82.5 to 93.5%. The retention of total
monomer anthocyanins were in the range of 3.9-42.3%. The antioxidant activity had
a final retention of 38.5-59.5%. In the simulated gastrointestinal digestion, a
maximum release was observed for the phenolic compounds in the intestinal phase
(90.6% for the spray-dried powder and 94.9% for the freeze-dried powder), as well
as the antioxidant activity (69.4% for the spray-dried powder and 67.8% for the
freeze-dried powder). However, a reduction of monomeric anthocyanins was observed
in the intestinal phase.
PMID- 28407910
TI - The membrane may be an important factor in browning of fresh-cut pear.
AB - Surface browning is an important cause of deterioration of fresh-cut fruit during
postharvest handling. In this paper, four pear cultivars with different extents
of natural browning were selected to analyse the factors involved in browning.
The main results are as follows: the lipoxygenase (LOX) activity of 'Mantianhong'
and 'Yali' pears was higher accompanied by a stronger degree of browning, while
the LOX activity in 'Xueqing' and 'Xinli 7' pears was lower, with less browning.
A higher unsaturated fatty acid ratio of pear resulted in reduced browning. The
cell membranes disappeared 30min after being cut in 'Mantianhong' pear, which
browns easily; however, the cell membranes were still intact 30min after being
cut in 'Xueqing' pear, which does not brown easily. Therefore, it can be assumed
that the stability of the cell membrane plays an important role in inhibiting
browning of fresh-cut pears.
PMID- 28407911
TI - Characterization of phenolics, glucosinolates and antioxidant activity of
beverages based on apple juice with addition of frozen and freeze-dried curly
kale leaves (Brassica oleracea L. var. acephala L.).
AB - The aim of this study was to determine the polyphenols, glucosinolates and
ascorbic acid content as well as antioxidant activity of beverages on the base of
apple juice with addition of frozen and freeze-dried curly kale leaves. Upon
enrichment with frozen (13%) and freeze-dried curly kale (3%), the naturally
cloudy apple juice was characterized by an increase in phenolic compounds by 2.7
and 3.3-times, accordingly. The antioxidant activity of beverages with the
addition of curly kale ranged from 6.6 to 9.4MUmol Trolox/mL. The obtained
beverages were characterized glucosinolates content at 117.6-167.6mg/L and
ascorbic acid content at 4,1-31,9mg/L. The results of sensory evaluation of
colour, taste and consistency of apple juice and beverages with the addition of
kale did not differ significantly prior to pasteurization (P<=0.05), whereas
after the pasteurization the evaluated factors decreased significantly.
PMID- 28407912
TI - Chemical composition of edible aerial parts of meadow bistort (Persicaria
bistorta (L.) Samp.).
AB - Persicaria bistorta (syn. Polygonum bistorta) is a herbaceous plant native to
Europe and Asia. The leaves, young shoots or aerial parts of bistort are one of
the main ingredients in a savoury pudding common to parts of the North of
England. The aim of the present study was to investigate the chemical composition
of extracts from aerial parts of common bistort. The UHPLC method allowed the
detection of thirty-five major and minor compounds in the analysed plant
material. Major constituents were isolated and identified. Two new natural
products were obtained namely quercetin and kaempferol 3-O-(5"-O-malonyl)-alpha-l
arabinofuranosides. The bioactivity assays showed that isolated malonylated
flavonoids inhibit the production of reactive oxygen species (IC50 in the range
22.4-40.6MUM) and myeloperoxidase release (IC50 in the range 22.2-32.2MUM) from
stimulated human neutrophils. Aerial parts of P. bistorta are a rich source of
polyphenols and some of them have anti-inflammatory potential.
PMID- 28407913
TI - Pyrroloquinoline quinone from Gluconobacter oxydans fermentation broth enhances
superoxide anion-scavenging capacity of Cu/Zn-SOD.
AB - A bioassay-guided fractionation of extract from Gluconobacter oxydans
fermentation broth afforded Compound 1, which was identified as pyrroloquinoline
quinone (PQQ) by spectroscopic methods. PQQ has been shown to enhance the
superoxide anion-scavenging capacity significantly for Cu/Zn-SOD. To illustrate
the mechanism, the interaction between PQQ and Cu/Zn-SOD was investigated. The
multiple binding sites involving hydrogen bonds and van der Waals force between
PQQ and Cu/Zn-SOD were revealed by isothermal titration calorimetry. The alpha
helix content was increased in the Cu/Zn-SOD structure with the addition of PQQ
into the solution through ultraviolet (UV) spectroscopy. These results indicated
that PQQ could change the conformation of Cu/Zn-SOD through interaction, which
could enhance its superoxide anion-scavenging capacity. Therefore, PQQ is a
potential natural antioxidant.
PMID- 28407914
TI - Effects of hybrid (microwave-convectional) and convectional drying on drying
kinetics, total phenolics, antioxidant capacity, vitamin C, color and rehydration
capacity of sour cherries.
AB - Sour cherries were dried by convectional (CD) at 50, 60, and 70 degrees C and by
hybrid (HD; microwave-convectional) drying at 120, 150, and 180W coupled with hot
air at 50, 60, and 70 degrees C. In HD, microwave power and hot air were
performed simultaneously during drying process. Total phenolic content (TPC),
antioxidant capacity (AOC), vitamin C content, color and rehydration capacity
were followed. The HD technique reduced drying time and increased drying rate
compared to CD. Drying data were well correlated with Verma and modified Logistic
models which gave the best fitting for CD and HD, respectively. The modified
Logistic model has never been used in food drying areas up to now. The higher
TPC, AOC, vitamin C content and rehydration ability were obtained from HD. Color
parameters had similar values for both drying methods. The HD technique can be
accepted as an alternative drying technique for sour cherry.
PMID- 28407915
TI - Distribution of apparent activation energy counterparts during thermo - And
thermo-oxidative degradation of Aronia melanocarpa (black chokeberry).
AB - Kinetics of degradation for Aronia melanocarpa fresh fruits in argon and air
atmospheres were investigated. The investigation was based on probability
distributions of apparent activation energy of counterparts (epsilona).
Isoconversional analysis results indicated that the degradation process in an
inert atmosphere was governed by decomposition reactions of esterified compounds.
Also, based on same kinetics approach, it was assumed that in an air atmosphere,
the primary compound in degradation pathways could be anthocyanins, which undergo
rapid chemical reactions. A new model of reactivity demonstrated that, under
inert atmospheres, expectation values for epsilona occured at levels of
statistical probability. These values corresponded to decomposition processes in
which polyphenolic compounds might be involved. epsilona values obeyed laws of
binomial distribution. It was established that, for thermo-oxidative degradation,
Poisson distribution represented a very successful approximation for epsilona
values where there was additional mechanistic complexity and the binomial
distribution was no longer valid.
PMID- 28407916
TI - Protective property of mulberry digest against oxidative stress - A potential
approach to ameliorate dietary acrylamide-induced cytotoxicity.
AB - The aim of this study was investigating the protective effect of mulberry digest
(MBD) on acrylamide-induced oxidative stress. Composition analysis of MBD
revealed that it contained six major phenolic compounds (quercetin-3-O
rutinoside, quercetin hexoside, quercetin rhamnosylhexoside hexoside, kaempferol
rhamnosylhexoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside). After in
vitro digestion, the contents of two anthocyanins were both decreased
significantly, while the contents of four flavonoid glycosides were all
increased. In addition, MBD was found to successfully suppress acrylamide-induced
ROS overproduction, restore the mitochondrial membrane potential, and inhibit the
mitochondrial membrane lipid peroxidation and glutathione depletion. More
interestingly, the protective effect of MBD against acrylamide-induced oxidative
damage was enhanced compared with mulberry fruits without digestion (MBE).
Further study revealed that MBD enhanced the cell resistance capacity to
acrylamide-induced oxidative stress, rather than its direct reaction with
acrylamide. Overall, our results indicate that MBD provides a potent protection
against acrylamide-induced oxidative stress.
PMID- 28407917
TI - Comprehensive comparative analysis of volatile compounds in citrus fruits of
different species.
AB - The volatile profiles of fruit peels and juice sacs from 108 citrus accessions
representing seven species were analyzed. Using GC-MS 162 and 107 compounds were
determined in the peels and juice sacs, respectively. In the peels, monoterpene
alcohols were accumulated in loose-skin mandarins; clementine tangerines and
papedas were rich in sesquiterpene alcohols, sesquiterpenes, monoterpene alcohols
and monoterpene aldehydes. beta-pinene and sabinene were specifically accumulated
in 4 of 5 lemon germplasms. Furthermore, concentrations of 34 distinctive
compounds were selected to best represent the volatile profiles of seven species
for HCA analysis, and the clustering results were in agreement with classic
citrus taxonomy. Comparison of profiles from different growing seasons and
production areas indicated that environmental factors play important roles in
volatile metabolism. In addition, a few citrus germplasms that accumulated
certain compounds were determined as promising breeding materials. Notably,
volatile biosynthesis via MVA pathway in C. ichangensis 'Huaihua' was enhanced.
PMID- 28407918
TI - Nickel speciation in cocoa infusions using monolithic chromatography - Post
column ID-ICP-MS and Q-TOF-MS.
AB - Nickel (Ni) is considered to be a potentially harmful element for humans. Its
levels in foodstuffs are normally low (below 0.2mgkg-1), but sensitive
individuals may develop allergy to Ni as a result of dietary consumption. Cocoa
contains relatively high Ni concentrations (around 3mgkg-1). Ni bioavailability,
its role in the flavour of food and its potential impact on human health depends
primarily on its chemical species. However, there is a lack of information about
Ni speciation in cocoa. In this work Ni species were separated on a weak
convective interaction media diethylamine (CIM DEAE) monolithic chromatographic
column and quantified by the post-column isotope dilution inductively coupled
plasma mass spectrometry (ID-ICP-MS). The Ni binding ligands in the separated
fractions were identified "off line" by quadrupole time-of-flight mass
spectrometry (Q-TOF MS). Ni was found to be present in the cocoa infusions as
Ni2+ and Ni-gluconate and Ni-citrate complexes.
PMID- 28407919
TI - Analytical validation of an ultraviolet-visible procedure for determining lutein
concentration and application to lutein-loaded nanoparticles.
AB - Lutein is a carotenoid presenting known anti-inflammatory and antioxidant
properties. Lutein-rich diets have been associated with neurological improvement
as well as reduction of the risk of vision loss due to Age-Related Macular
Degeneration (AMD). Micro and nanoencapsulation have demonstrated to be effective
techniques in protecting lutein against degradation and also in improving its
bioavailability. However, actual lutein concentration inside the capsules and
encapsulation efficiency are key parameters that must be precisely known when
designing in vitro and in vivo tests. In this work an analytical procedure was
validated for the determination of the actual lutein content in zein
nanoparticles using ultraviolet-visible spectroscopy. Method validation followed
the International Conference on Harmonisation (ICH) guidelines which evaluate
linearity, detection limit, quantification limit, accuracy and precision. The
validated methodology was applied to characterize lutein-loaded nanoparticles.
PMID- 28407920
TI - Preharvest application of oxalic acid improves quality and phytochemical content
of artichoke (Cynara scolymus L.) at harvest and during storage.
AB - In this study the effect of oxalic acid (OA) treatment of artichoke plants
(Cynara scolymus L.) on head artichoke development and on artichokes quality
parameters (weight loss, firmness, and color), respiration rate, antioxidant
activity and phenolics (measured by Folin Ciocalteu and HPLC-DAD-ESI/MSn) at
harvest and during storage for 21days at 2 degrees C was evaluated. OA treatment
increased the percentage of the first class artichokes although no significant
effect was found in artichoke developmental process. OA-treatment reduced the
respiration rate of artichokes and led to higher total hydrosoluble antioxidant
activity and total phenolics and hydroxycinnamics and luteolins concentration
both at harvest and during cold storage. In addition, luteolin 7-O-glucuronide 3
O-glucoside was identified for the first time in artichoke. Thus, it can be
concluded that OA preharvest treatment could be a natural and useful tool to
delay the artichoke postharvest senescence and improve the reported health
beneficial properties of artichokes consumption.
PMID- 28407921
TI - Enhanced production of pleuromutilin by Pleurotus mutilus and study on its
molecular structure.
AB - This study aims to enhance the accumulation of pleuromutilin by Pleurotus mutilus
and to analyze the molecular structure of pleuromutilin. The results showed that
a novel three-stage DO control strategy (60% DO, 1-3d; 45% DO, 4-6d; 30% DO, 7
9d) was very effective for improving the pleuromutilin accumulation and the
highest production reached 12g/L, a 4-fold increase over a constant DO strategy.
Furthermore, the flow behavior of fermentation broth appeared Newtonian with a
maximum MUap of 3.9*10-3Pa.s. Meanwhile the molecular formula (C22H34O5),
molecular weight (378.5) and structural formula of pleuromutilin were concluded
based on spectroscopy and element assay. The main components were hydroxyl,
methyl, methylene, carbonyl, carboxyl, and polycyclic hydrocarbon. This work
demonstrated that DO strategy was suitable for scalable production of
pleuromutilin, which makes pleuromutilin more affordable as materials in food.
PMID- 28407922
TI - Continuous extraction of phenolic compounds from pomegranate peel using high
voltage electrical discharge.
AB - Pomegranate peel, a waste generated from fruit processing industry, is a
potential source of phenolic compounds that are known for their anti-oxidative
properties. In this study, a continuous high voltage electrical discharge (HVED)
extraction system was for the first time designed and optimized for phenolic
compounds from pomegranate peel. The optimal conditions for HVED were: flow rate
of materials 12mL/min, electrodes gap distance 3.1mm (corresponding to 29kV/cm of
electric field intensity) and liquid to solid ratio 35mL/g. Under these
conditions, the experimental yield of phenolic compounds was 196.7+/-6.4mg/g,
which closely agreed with the predicted value (199.83mg/g). Compared with the
warm water maceration, HVED method possessed higher efficiency for the extraction
of phenolic compounds. The results demonstrated that HVED technique could be a
very effective method for continuous extraction of natural compounds.
PMID- 28407923
TI - Simultaneous separation and purification of chlorogenic acid, epicatechin,
hyperoside and phlorizin from thinned young Qinguan apples by successive use of
polyethylene and polyamide resins.
AB - The method for separating and purifying chlorogenic acid (CA), epicatechin (EC),
hyperoside (HY) and phlorizin (PH) simutaneously from young Qinguan apples by
successive use of X-5 and polyamide resins has been developed in this study. The
order of adsorption capacities of X-5 for the four phenolics was PH>HY>EC>CA, and
the adsorption equilibriums of the four phenolics onto X-5 resin conformed to
Langmuir isotherms preferentially. The adsorption kinetics of EC and CA onto X-5
conformed to the pseudo-first-order model, while that of HY and PH accorded with
the pseudo-second-order model. Interestingly, the values of equilibrium
adsorption capacities (Qe) calculated in the preferential kinetics models were
closer to that of theoretical maximum adsorption capacities (Q0) calculated by
Langmuir isotherms. Through dynamic adsorption and desorption using X-5 and
polyamide resins with ethanol solution as strippant, CA, EC, HY and PH were
obtained with purities of 96.21%, 95.34%, 95.36% and 97.36%, respectively.
PMID- 28407924
TI - Validated method for the determination of propane-1,2-diol, butane-2,3-diol, and
propane-1,3-diol in cheese and bacterial cultures using phenylboronic
esterification and GC-MS.
AB - A simple, fast, sensitive, and robust gas chromatography-mass spectrometry (GC
MS) method for the simultaneous determination of propane-1,2-diol, butane-2,3
diol, and propane-1,3-diol in cheese and bacterial cultures was developed. Target
analytes were extracted and transformed into their phenylboronic esters prior to
analysis. The method showed good sensitivity, without carryover between the
samples. The detection limits for propane-1,2-diol, butane-2,3-diol, and propane
1,3-diol in cheese samples were 0.26, 0.02, and 0.11mgkg-1, respectively, and for
bacterial culture samples were 1.32, 0.09, and 0.54mgkg-1, respectively. The
Horwitz ratio showed good precision for all analytes (<0.45). The calibrated
range in cheese for all analytes was very broad, from 0 to 1000mgkg-1, and in
bacterial cultures was from 0 to 5000mgkg-1 with R2>0.9991. The results confirm
excellent applicability of the proposed method for the determination of the
target metabolites in cheese and bacterial culture samples.
PMID- 28407925
TI - DNA adductomics to study the genotoxic effects of red meat consumption with and
without added animal fat in rats.
AB - Digestion of red and processed meat has been linked to the formation of genotoxic
N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs) in the gut. In
this study, rats were fed a meat based diet to compare the possible genotoxic
effects of red vs. white meat, and the interfering role of dietary fat. To this
purpose, liver, duodenum and colon DNA adductomes were analyzed with UHPLC-HRMS.
The results demonstrate that the consumed meat type alters the DNA adductome; the
levels of 22 different DNA adduct types significantly increased upon the
consumption of beef (compared to chicken) and/or lard supplemented beef or
chicken. Furthermore, the chemical constitution of the retrieved DNA adducts hint
at a direct link with an increase in NOCs and LPOs upon red (and processed) meat
digestion, supporting the current hypotheses on the causal link between red and
processed meat consumption and the development of colorectal cancer.
PMID- 28407926
TI - Preconcentration and trace determination of copper (II) in Thai food recipes
using Fe3O4@Chi-GQDs nanocomposites as a new magnetic adsorbent.
AB - This study describes the preparation, characterization, and application of a new
magnetic chitosan-graphene quantum dots (Fe3O4@Chi-GQDs) nanocomposite as an
adsorbent for the preconcentration of Cu(II) in Thai food recipes or the so
called "Som Tam" (green papaya salad) prior to determination by inductively
coupled plasma-optical emission spectrometry. The spectroscopic and magnetic
properties along with the morphology and thermal property were analyzed using
FTIR, EDX, XRD, TGA, VSM, and TEM. Preconcentration optimizations including pH,
dosage of adsorbent, adsorption-desorption time, concentration and volume of
elution solvent, sample volume and enrichment factor, and reusing time were
investigated. Good linearity was obtained ranging from 0.05 to 1500ugL-1 with
correlation coefficient of 0.999. Limit of detection was 0.015ugL-1. Relative
recoveries of 85.4-107.5% were satisfactorily obtained. This Fe3O4@Chi-GQDs has
high potential to be used as preconcentration method and can be reused 7times
with high extraction efficiency.
PMID- 28407927
TI - Using bio-dispersive solution of chitosan for green dispersive liquid-liquid
microextraction of trace amounts of Cu(II) in edible oils prior to analysis by
ICP-OES.
AB - A green approach using chitosan solution as a novel bio-dispersive agent for the
dispersive liquid-liquid microextraction (DLLME) of trace amounts of Cu(II) in
edible oils is presented. An emulsion was formed by mixing the oil sample with
300uL of 0.25% (w/v) chitosan solution containing 200uL of 6molL-1 HCl. Deionized
water was used to induce emulsion breaking without centrifugation. The
centrifuged Cu(II) extract was collected and analyzed using an inductively
coupled plasma-optical emission spectrometer. The detection and quantitation
limits were 2.1 and 6.8ugL-1, respectively. Trace amounts of Cu(II) in six edible
oil samples were tested under optimum conditions for DLLME, with a recovery
ranging from 90.3% to 109.3%. Therefore, the new dispersive agent in DLLME offers
superior performance owing to the non-toxic nature of the solvent, short
extraction time, high sensitivity, and easy operation.
PMID- 28407928
TI - Wild mushrooms and their mycelia as sources of bioactive compounds: Antioxidant,
anti-inflammatory and cytotoxic properties.
AB - Mushrooms are important sources of natural bioactive compounds. Pleurotus eryngii
(DC.) Quel is recognized for its organoleptic quality and health effects, being
extensively commercialized. Instead, Suillus bellinii (Inzenga) Watling is an
ectomycorrhizal symbiont, whose main properties were scarcely reported.
Considering current trends, the mycelia and the culture media of these mushrooms
might be potential sources of bioactive compounds. Accordingly, P. eryngii and S.
bellinii were studied for their phenolic acids and sterols, antioxidant capacity,
anti-inflammatory effect and anti-proliferative activity. S. bellinii mycelia
showed higher contents of ergosterol and phenolic compounds (also higher in its
fruiting body) and stronger antioxidant activity than P. eryngii. Conversely, P.
eryngii mycelia showed anti-inflammatory (absent in S. bellinii mycelia) and a
cytotoxicity similar (sometimes superior) to its fruiting bodies, contrarily to
S. bellinii. Furthermore, the assayed species showed differences in the growth
rate and produced mycelia, which should be considered in further applications.
PMID- 28407930
TI - Large-scale multi-class herbicides analysis in oilseeds by rapid one-step
QuEChERS-based extraction and cleanup method using liquid chromatography-tandem
mass spectrometry.
AB - A simple, sensitive and rapid method is proposed for simultaneous determination
of 120 various classes of herbicides in oilseed samples. A one-step QuEChERS
based approach to extraction and cleanup has been developed. LC-MS/MS was used to
evaluate the proposed sample treatment methodologies. The new one-step QuEChERS
strategy was compared to other methodologies previously used for elimination of
co-extracts from fatty matrices. For validation purposes, recovery studies were
carried out at 5, 50 and 500ugkg-1 levels for rapeseed, sunflower seeds and
soybean. The optimized method yielded a small matrix effect (-20-20%) for 82% of
the tested compounds. We was found to reduce matrix effects more effectively
without significantly decreasing analyte recoveries. Throughout the validation
experiments, 70-120% overall recoveries were achieved with RSDs<20% for most
herbicides. The validated method was employed in analysis of ninety real rapeseed
samples.
PMID- 28407929
TI - Filter-vial dispersive solid-phase extraction as a simplified clean-up for
determination of ethylphenols in red wines.
AB - In-vial filtration with dispersive solid-phase extraction (d-SPE) clean-up of
QuEChERS (quick, easy, cheap, effective, rugged and safe) extracts is proposed
for the determination of ethylphenols (EPs) in red wines. Analytes were extracted
from 5mL wine sample (previously alkalinized with 0.5% sodium hydroxide) using
5mL acetonitrile. For phase separation, 1.5g NaCl and 4g anhydrous MgSO4 were
added. Then, a 0.5mL aliquot of the partitioned supernatant was cleaned-up using
d-SPE and in-vial filtration with a combination of anhydrous CaCl2 (100mg) and
primary-secondary amine (PSA, 25mg) as sorbents. The proposed method provided
limits of quantification (LOQs) ranging from 0.024 to 0.04mgL-1. Considering
matrix-matched calibration as quantification technique, the recoveries (accuracy)
ranged between 73% and 116%. The method was applied for the determination of EPs
in 15 commercial wines of Argentina, where 4-EP was quantified at concentrations
ranging from 0.25 to 3.01mgL-1.
PMID- 28407931
TI - Multi-pesticides residue analysis of grains using modified magnetic nanoparticle
adsorbent for facile and efficient cleanup.
AB - A facile, rapid sample pretreatment method was developed based on magnetic
nanoparticles for multi-pesticides residue analysis of grains. Magnetite (Fe3O4)
nanoparticles modified with 3-(N,N-diethylamino)propyltrimethoxysilane (Fe3O4
PSA) and commercial C18 were selected as the cleanup adsorbents to remove the
target interferences of the matrix, such as fatty acids and non-polar compounds.
Rice was used as the representative grain sample for method optimization. The
amount of Fe3O4-PSA and C18 were systematically investigated for selecting the
suitable purification conditions, and the simultaneous determination of 50
pesticides and 8 related metabolites in rice was established by liquid
chromatography-tandem mass spectrometry. Under the optimal conditions, the method
validation was performed including linearity, sensitivity, matrix effect,
recovery and precision, which all satisfy the requirement for pesticides residue
analysis. Compared to the conventional QuEChERS method with non-magnetic material
as cleanup adsorbent, the present method can save 30% of the pretreatment time,
giving the high throughput analysis possible.
PMID- 28407932
TI - A G-quadruplex based fluorescent oligonucleotide turn-on probe towards iodides
detection in real samples.
AB - A basket-type G-quadruplex (GQ) fluorescent oligonucleotide (OND) probe is
designed to detect iodides dependent on thymine-Hg(II)-thymine (T-Hg(II)-T) base
pairs and the intrinsic fluorescence quenching capacity of GQ. In the presence of
Hg(II) ions (Hg2+), the two hexachloro-fluorescein-labeled ONDs form a hairpin
structure and the fluorophores are dragged close to the GQ, leading to
fluorescence quenching of the probe due to photoinduced electron transfer. Upon
addition of iodide anions, Hg2+ are extracted from T-Hg(II)-T complexes which
attributes to the stronger binding with iodide anions, resulting in the
fluorescence recovery. Through performing the fluorescence quenching and recovery
processes, this probe developed a fluorescence turn-on sensor for iodide anions
determination over a linear range of 20-200nmol/L with a limit of detection of
5nmol/L. The practical use of the turn-on technology was demonstrated by its
application in determination of iodides in water, food, pharmaceutical products
and biological samples.
PMID- 28407933
TI - Influence of postharvest treatments on qualitative and chemical parameters of
Tarocco blood orange fruits to be used for fresh chilled juice.
AB - Tarocco "Sant'Alfio" is a late ripening blood orange cultivar. Blood oranges are
more and more appreciated from consumers for their high nutraceutical value due
to the presence of bioactive compounds including vitamin C, polyphenols,
flavonoids and hydroxycinnamic acids. The aim of this work is to set up a
reliable protocol for postharvest storage of the very-late Tarocco "Sant'Alfio"
orange to prolong the availability of this product in the market to be used for
fresh chilled orange juice production. Fruits were subjected to three storage
treatments (20days at 1 degrees C plus 50days at 4 degrees C; 70days at 4 degrees
C; 70days at 20 degrees C). The results indicate that cold treatments, in
particular at 4 degrees C constantly, can extend Tarocco "Sant'Alfio" shelf life
enhancing total anthocyanin content. The defined protocols allow prolonging
market availability of a high value product and could induce relevant benefits
for the citrus industry and consumers.
PMID- 28407934
TI - Organophosphorus pesticides determination by novel HPLC and spectrophotometric
method.
AB - The present work describes a novel HPLC and UV-spectrophotometric method for the
simultaneous estimation of chlorpyrifos and prophenofos in vegetables and fruits.
In UV method, the absorbance of chlorpyrifos and prophenofos was measured at
wavelength 277nm and 289nm respectively and quantitation was carried out by first
order derivative method. The calibration curve for chlorpyriphos and prophenofos
was found to be linear in the range of 6-16MUg/mL with correlation coefficient
0.9979 and 0.9993 respectively. The HPLC separation was achieved on Hibar C18
column (250*4.6mm, 5u) using mobile phase consist of acetonitrile: water (90:10,
v/v) at flow rate 1.0mL/min and the eluent was monitored at 219nm. Pesticides
were extracted from the samples by solid phase extraction and liquid-liquid
extraction before the analysis. Out of these two extraction methods, solid phase
extraction was found more efficient in terms of % recovery as compared to liquid
liquid extraction. The developed method was applied for estimation of
chlorpyrifos and prophenofos and it was found that the chlorpyrifos was
0.018mg/kg, which is above maximum residue limits (0.01mg/kg), which might be
toxic to body. Prophenofos was not found in any collected samples of vegetables
and fruits.
PMID- 28407935
TI - Omega-3 PUFA concentration by a novel PVDF nano-composite membrane filled with
nano-porous silica particles.
AB - : In this study, polyvinylidene fluoride (PVDF) and nano-porous silica particle
were used to fabricate an asymmetric nano-composite membrane. Silica particles
enhanced the thermal stability of PVDF/SiO2 membranes; increasing the
decomposition temperature from 371 degrees C to 408 degrees C. Cross sectional
morphology showed that silica particles were dispersed in polymer matrix
uniformly. However, particle agglomeration was found at higher loading of silica
(i.e., 20 by weight%). The separation performance of nano-composite membranes was
also evaluated using the omega-3 polyunsaturated fatty acids (PUFA) concentration
at a temperature and pressure of 30 degrees C and 4bar, respectively. Silica
particle increased the omega-3PUFA concentration from 34.8 by weight% in neat
PVDF to 53.9 by weight% in PVDF with 15 by weight% of silica. Moreover, PVDF/SiO2
nano-composite membranes exhibited enhanced anti-fouling property compared to
neat PVDF membrane. Fouling mechanism analysis revealed that complete pore
blocking was the predominant mechanism occurring in oil filtration. INDUSTRIAL
RELEVANCE: The concentration of omega-3 polyunsaturated fatty acids (PUFA) is
important in the oil industries. While the current methods demand high energy
consumptions in concentrating the omega-3, membrane separation technology offers
noticeable advantages in producing pure omega-3 PUFA. Moreover, concentrating
omega-3 via membrane separation produces products in the triacylglycerol form
which possess better oxidative stability. In this work, the detailed mechanisms
of fouling which limits the performance of membrane separation were investigated.
Incorporating silica particles to polymeric membrane resulted in the formation of
mixed matrix membrane with improved anti-fouling behaviour compared to the neat
polymeric membrane. Hence, the industrial potential of membrane processing to
concentrate omega-3 fatty acids is enhanced.
PMID- 28407936
TI - Optimization of the recovery of high-value compounds from pitaya fruit by
products using microwave-assisted extraction.
AB - A green microwave-assisted extraction of high value-added compounds from exotic
fruits' peels was optimized by Box-Behnken design using 3 factors: solid/solvent
ratio, X1, temperature, X2, and extraction time, X3. By using Derringer's
desirability function, optimum extraction yields are obtained with
X1=1/149.95g/mL, X2=72.27 degrees C and X3=39.39min (white-fleshed red pitaya)
and X1=1/148.96g/mL, X2=72.56 degrees C and X3=5.02min (yellow pitaya) and a
maximum betacyanin content is achieved with X1=1/150g/mL, X2=49.33 degrees C and
X3=5min. None of the factors influenced the extraction of phenolic compounds.
Eighteen cinnamoyl derivatives, 17 flavonoid derivatives and 4 betacyanins were
identified by HPLC-DAD-ESI/MSn, 23 and 15 new compounds being described in yellow
and white-fleshed red pitayas, respectively. These results indicate that it is
possible to reuse these by-products to recover compounds for food and
pharmaceutical industries.
PMID- 28407937
TI - Myofibrillar protein gel properties are influenced by oxygen concentration in
modified atmosphere packaged minced beef.
AB - Minced beef was stored for 8days and myofibrillar protein (MP) was extracted to
investigate the effect of oxygen concentration (0, 20, 40, 60, and 80%) in
modified atmosphere packaging (MAP) on heat-induced gel properties. Compression
force of gels was lower when prepared from beef packaged in 0% oxygen,
intermediate in 20 to 60% oxygen and greater in 80% oxygen. Total water loss of
gels prepared from beef packaged with oxygen (20-80%) was higher and rheology
measurements presented higher G' and G" values. Additionally, gels from beef
packaged without oxygen exhibited higher J (t) values during creep and recovery
tests, demonstrating that oxygen exposure of meat during storage in MAP affect MP
in such a way that heat-induced protein gels alter their characteristics.
Generally, storage with oxygen in MAP resulted in stronger and more elastic MP
gels, which was observed already at a relative low oxygen concentration of 20%.
PMID- 28407938
TI - Eventual limits of the current EU official method for evaluating milk
adulteration of water buffalo dairy products and potential proteomic solutions.
AB - The European reference method (ERM) recognises the fraudulent addition of bovine
(B) milk in water buffalo (WB) milk/dairy products based on concomitant
isoelectric focusing (IEF) detection of B gamma2- and gamma3-CN fragments after
corresponding plasminolysis. We here used proteomics to characterise false
positive results occurring in the ERM as being due to WB beta-CN(f100-209), which
is also formed after plasminolysis of genuine WB milk/dairy products and
comigrates in IEF with B gamma2-CN. These ERM limitations were overcome by a
dedicated proteomic procedure based on loading of B/WB milk/cheese CN extracts on
a hydroxyapatite column, in situ trypsinolysis and elution of B beta-CN(f1-25)4P
and WB beta-CN(f1-28)4P proteotypic peptides. Based on their similar ionisation
properties and resolution in MALDI-TOF-MS, these phosphopeptides were identified
as suitable markers for detection of B material in WB milk/dairy products to a
detection limit of 0.8% v/v. This proteomic procedure is here proposed as
integrative/alternative to the ERM.
PMID- 28407939
TI - DNA barcoding coupled to HRM analysis as a new and simple tool for the
authentication of Gadidae fish species.
AB - This work aimed to exploit the use of DNA mini-barcodes combined with high
resolution melting (HRM) for the authentication of gadoid species: Atlantic cod
(Gadus morhua), Pacific cod (Gadus macrocephalus), Alaska pollock (Theragra
chalcogramma) and saithe (Pollachius virens). Two DNA barcode regions, namely
cytochrome c oxidase subunit I (COI) and cytochrome b (cytb), were analysed in
silico to identify genetic variability among the four species and used,
subsequently, to develop a real-time PCR method coupled with HRM analysis. The
cytb mini-barcode enabled best discrimination of the target species with a high
level of confidence (99.3%). The approach was applied successfully to identify
gadoid species in 30 fish-containing foods, 30% of which were not as declared on
the label. Herein, a novel approach for rapid, simple and cost-effective
discrimination/clustering, as a tool to authenticate Gadidae fish species,
according to their genetic relationship, is proposed.
PMID- 28407940
TI - Natural occurrence of tenuazonic acid and Phoma sorghina in Brazilian sorghum
grains at different maturity stages.
AB - A survey of 100 samples of sorghum grains was carried out to determine Phoma spp.
and tenuazonic acid (TA) contamination using molecular tools and LC-MS/MS.
Sorghum samples were obtained at the following four grain maturity stages: milk
(S1), soft dough (S2), hard dough (S3), and physiological maturity (S4). The
results revealed a good correlation between Phoma and TA occurrence during grain
development. The samples showed Phoma contamination with frequencies ranging from
2.4% (S1) to 87.4% (S4), and the molecular identification revealed P. sorghina as
the only Phoma specie isolated. Tenuazonic acid was found in sorghum grains at
all maturity stages. In S2, S3 and S4, 100% of the samples showed TA
contamination with levels ranging from 20 to 1234ug/kg. Low levels of TA were
detected in 36% of the samples collected at S1 stage. This is the first report of
tenuazonic acid in Brazilian sorghum grains.
PMID- 28407941
TI - Screening and identification of per- and polyfluoroalkyl substances in microwave
popcorn bags.
AB - Liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC
QToF-MS) was used for the accurate identification (<10ppm) of different
polyfluoroalkylphosphates (PAPs) and their intermediate and end degradation
products in popcorn bags. Up to 46 per- and polyfluoroalkyl substances (PFASs)
and precursors were identified. Moreover, an accurate method based on focused
ultrasonic solid-liquid extraction (FUSLE) and a clean-up step with Envi-Carb
sorbent was validated and applied to the quantification of 24 PFASs in popcorn
bags from over twelve European countries, three American countries and two Asian
countries. To the best of our knowledge, this is the first time that
identification and quantification of some intermediates of PFAS precursors
(different chain length fluorotelomer saturated acids (FTCAs) and fluorotelomer
unsaturated acids (FTUCAs)) have been reported. Moreover, different patterns in
the microwave popcorn bag composition were observed within the countries; while
in European and American countries short chain PFASs were detected, Asian
countries still use long chain PFASs.
PMID- 28407942
TI - Effect of ultrasound pretreatment and Maillard reaction on structure and
antioxidant properties of ultrafiltrated smooth-hound viscera proteins-sucrose
conjugates.
AB - The effect of ultrasound (US) pre-treatment on the evolution of Maillard reaction
(MR), induced between low molecular weight (LMW) peptides and sucrose, was
studied. LMW peptides (<1kDa) were obtained by the ultrafiltration of smooth
hound viscera protein hydrolysates, produced by Neutrase, Esperase and Purafect.
MR was induced by heating the LMW peptides in the presence of sucrose for 2h at
90 degrees C, without or with US pre-treatment. During the reaction, a marked
decrease in pH values, coupled to the increase in colour of the Maillard reaction
products (MRPs), were recorded. In addition, after sonication, the glycation
degree was significantly enhanced in Esperase-derived peptides/sucrose conjugates
(p<0.05). Moreover, results showed that thermal heating, particularly after US
treatment, reduced the bitter taste and enhanced the antioxidant capacities of
the resulting conjugates. Hence, it could be concluded that US leads to efficient
mixing of sugar-protein solution and efficient heat/mass transfer, contributing
to increase the MR rate.
PMID- 28407943
TI - Effects of oligosaccharides on pasting, thermal and rheological properties of
sweet potato starch.
AB - Effects of sucrose, raffinose and stachyose on pasting, thermal, and rheological
properties of sweet potato starch (SPS) were investigated. The results indicated
that pasting temperature of SPS increased with increasing sugar concentration in
the order of stachyose>raffinose>sucrose. Addition of sugars significantly
decreased the peak, trough, and final viscosities as well as setback value. The
gelatinization temperatures of SPS-sugar mixtures markedly increased with
increasing sugar concentration in the order of stachyose>raffinose=sucrose,
gelatinization enthalpy also increased when sugar was added at high concentration
compared with native starch. The addition of sugars increased the yield stress
and consistency coefficient of SPS-sugar mixed pastes. The SPS-sugar mixed pastes
exhibited a pseudoplastic and shear-thinning behavior under yield stress
condition. Moreover, storage moduli (G') of SPS-sugar mixed pastes decreased with
addition of sugars. This study also showed that addition of sugars promoted
liquid-like characteristics of SPS-sugar mixed pastes.
PMID- 28407944
TI - Clean-up and matrix effect in LC-MS/MS analysis of food of plant origin for high
polar herbicides.
AB - This study reports an innovative and sensitive procedure for analysis of
difficult high polar herbicides (HPH) in diverse foods of plant origin. The QuPPe
(Quick Polar Pesticides) method followed by determination by LC-MS/MS was
modified. Chromatographic conditions, extraction, clean-up, and matrix effect
were studied. Several liquid chromatography stationary and mobile phases were
evaluated, and it was found that hydrophilic interaction chromatography (HILIC)
gives good retention and sensitivity. An acidified methanol-water mixture was
used as an effective extraction solvent of eleven HPH. Dispersive solid-phase
clean-up sorbents (C18, GCB, Florisil, chitosan and graphene) were evaluated. The
efficiency of the method was examined using data on recovery, precision and
matrix effects. High extraction yields were achieved, and recoveries were within
the 64-97% range with relative standard deviations <20% for all HPH in all
commodities. Low matrix effects were observed when graphene was used during clean
up of onion extract and when chitosan was used for wheat, potato and pea extract.
PMID- 28407945
TI - Shelf life extension of whole-wheat breadsticks: Formulation and packaging
strategies.
AB - The aim of this study was the shelf life extension of whole-wheat breadsticks
through the addition of a rosemary extract and packaging under nitrogen. Shelf
life was studied at four temperatures (20, 27, 35, 48 degrees C) for up to 200
storage days. The minimal changes observed in moisture, water activity and
texture of the samples, coupled with the high peroxide values (13-539meqO2/kgfat)
measured at the end of storage, and the exponential increase of hexanal
concentrations (up to 13-34mg/kg) confirmed that quality decay of whole-wheat
breadsticks is mainly associated to lipid oxidation. The kinetic study of
oxidation development and the consumer sensory acceptance determined by the
survival analysis demonstrated that the rosemary extract addition yields a 42%
shelf life extension, higher than that observed using nitrogen in the package (24
29%). The combination of the formulation and packaging strategies gave the best
result (83% shelf life extension at 25 degrees C).
PMID- 28407946
TI - Manuka honey (Leptospermum scoparium) inhibits jack bean urease activity due to
methylglyoxal and dihydroxyacetone.
AB - Manuka honey (Leptospermum scoparium) exerts a strong antibacterial effect.
Bacterial enzymes are an important target for antibacterial compounds. The enzyme
urease produces ammonia and enables bacteria to adapt to an acidic environment. A
new enzymatic assay, based on photometric detection of ammonia with ninhydrin,
was developed to study urease activity. Methylglyoxal (MGO) and its precursor
dihydroxyacetone (DHA), which are naturally present in manuka honey, were
identified as jack bean urease inhibitors with IC50 values of 2.8 and 5.0mM,
respectively. Urease inhibition of manuka honey correlates with its MGO and DHA
content. Non-manuka honeys, which lack MGO and DHA, showed significantly less
urease inhibition. MGO depletion from manuka honey with glyoxalase reduced urease
inhibition. Therefore, urease inhibition by manuka honey is mainly due to MGO and
DHA. The results obtained with jack bean urease as a model urease, may contribute
to the understanding of bacterial inhibition by manuka honey.
PMID- 28407947
TI - Tuneable surface enhanced Raman spectroscopy hyphenated to chemically derivatized
thin-layer chromatography plates for screening histamine in fish.
AB - Reliable screening of histamine in fish was of urgent importance for food safety.
This work presented a highly selective surface enhanced Raman spectroscopy (SERS)
method mediated by thin-layer chromatography (TLC), which was tailored for
identification and quantitation of histamine. Following separation and
derivatization with fluram, plates were assayed with SERS, jointly using silver
nanoparticle and NaCl. The latter dramatically suppressed the masking effect
caused by excessive fluram throughout the plate, thus offering clear baseline and
intensive Raman fingerprints specific to the analyte. Under optimized conditions,
the usability of this method was validated by identifying the structural
fingerprints of both targeted and unknown compounds in fish samples. Meanwhile,
the quantitative results of this method agreed with those by an HPLC method
officially suggested by EU for histamine determination. Showing remarkable cost
efficiency and user-friendliness, this facile TLC-SERS method was indeed
screening-oriented and may be more attractive to controlling laboratories of
limited resource.
PMID- 28407948
TI - Sensory and chemical drivers of wine minerality aroma: An application to Chablis
wines.
AB - The goal of this work was to evaluate the effect of vineyard position on the
minerality of wines and to establish relationships between minerality scores,
sensory descriptors and chemical composition. Sensory analyses included
minerality rating and free description performed by wine professionals under two
conditions: orthonasal olfaction alone and global tasting. Chemical
characterization included analysis of major and minor volatile compounds,
volatile sulphur compounds, mercaptans, metals, anions and cations. Results
showed a significant effect of the river bank on wine minerality scores only in
the orthonasal olfaction condition, samples from the left being more mineral than
those from the right bank. Methanethiol, involved in shellfish aroma, was
significantly higher in wines from the left (more mineral) than from the right
bank. Contrary, copper levels, related to lower levels of free MeSH, and
norisoprenoids, responsible for white fruit and floral aromas, were higher in
wines from the right bank (less mineral).
PMID- 28407949
TI - Direct technique for monitoring lipid oxidation in water-in-oil emulsions based
on micro-calorimetry.
AB - An experimental device based on the measurement of the heat flux dissipated
during chemical reactions, previously validated for monitoring lipid oxidation in
plant oils, was extended to follow lipid oxidation in water-in-oil emulsions.
Firstly, validation of the approach was performed by correlating conjugated diene
concentrations measured by spectrophotometry and the heat flux dissipated by
oxidation reactions and measured directly in water-in-oil emulsions, in
isothermal conditions at 60 degrees C. Secondly, several emulsions based on plant
oils differing in their n-3 fatty acid content were compared. The oxidability
parameter derived from the enthalpy curves reflected the alpha-linolenic acid
proportion in the oils. On the whole, the micro-calorimetry technique provides a
sensitive method to assess lipid oxidation in water-in-oil emulsions without
requiring any phase extraction.
PMID- 28407950
TI - DLLME-spectrophotometric determination of glyphosate residue in legumes.
AB - A new separation and pre-concentration method for spectrophotometric
determination of glyphosate herbicide was developed. Glyphosate was converted
into dithiocarbamic acid with CS2, followed by copper in the presence of ammonia
to promote complex formation. This complex was collected in a CH2Cl2 organic drop
and absorbance measured at 435nm. The analytical parameters, such as the amount
of NH3, Cu(II) and CS2, type of extraction solutions, and the ratio of dispersive
and organic liquids were optimized. The calibration curve was linear in the range
0.5-10mgl-1. The limits of detection and quantification were calculated from 3s
to 10s criterions as 0.21mgl-1 and 0.70mgl-1, respectively. The developed method
was applied to legume samples with the satisfactory recovery values of 98+/-4
102+/-3%.
PMID- 28407951
TI - Down scaled Kjeldahl digestion and flow injection conductometric system for
determination of protein content in some traditional northern Thai foods.
AB - A flow injection conductometric (FIC) system for determination of total Kjeldahl
nitrogen (TKN) was developed for estimating total protein content in food. A
small scale Kjeldahl digestion was performed with a short digestion time of only
20min. The digested solution was injected into the FIC system, and TKN was
converted to ammonia gas in an alkaline donor stream of the system. The gas
diffused through a membrane and dissolved into an acceptor stream causing an
increase in conductivity as detected by a detector and recorded as a peak. Under
the optimum condition, a linear calibration graph in the range of 4.00-100.00mgL
1 was obtained with LOD of 0.05mgL-1. A good precision (0.04% RSD, n=11,
30.00mgNL-1) and high sample throughput of 72h-1 was achieved. The method was
applied for determination of protein in some traditional northern Thai foods,
revealing that they are good sources of proteins.
PMID- 28407952
TI - Common food colorants and allergic reactions in children: Myth or reality?
AB - Various additives, including food colorants (FCs), are used in the food industry
to make food appealing to consumers and to add variety. Despite the widespread
usage of FCs, adverse reactions related to their consumption, including reactions
triggered by immune (immediate and delayed-type hypersensitivity) and non-immune
(intolerance) mechanisms, are considered rare. There is a discrepancy between the
perception of patients and parents (7.4%) and the reported prevalence of adverse
reactions to additives (0.01-0.23%), which is higher in atopic individuals (2
7%). Documented reactions are mild, involving mainly the skin, and, rarely,
anaphylaxis. A major problem in diagnosing reactions to FCs is identification of
the offending agent(s), which is based on careful dietary history taking. Allergy
testing is usually unrevealing, except for reaction to some natural colorants.
Treatment consists of avoidance of the offending colorant as no successful
desensitization procedures have been reported.
PMID- 28407953
TI - Antioxidant potential of edible mushroom (Agaricus bisporus) protein hydrolysates
and their ultrafiltration fractions.
AB - Mushroom protein isolate (MPI) from Agaricus bisporus was hydrolyzed using
Alcalase, Pancreatin, Flavourzyme, Alcalase-Pancreatin and Alcalase-Flavourzyme.
The obtained hydrolysates (MPHs) were ultrafiltered to generate peptide fractions
(UFs) of molecular sizes (<1, 1-3, 3-5 and 5-10kDa). The electrophoretic profile
results indicated that the enzymatic systems were efficient in hydrolyzing the
MPI into low molecular weight peptides. Hydrolysate yields of >57% and protein
recoveries of >43% were obtained. Effective concentration that scavenged 50%
(EC50) of DPPH radicals was similar for the MPHs while inhibition against
linoleic acid oxidation was strongest (66.49%) for Alcalase-Flavourzyme
hydrolysate on day 5 of incubation. UFs exhibited a concentration-dependent FRAP,
with the highest activity for fractions from Alcalase and Pancreatin recorded in
1-3kDa. The antioxidant activities of MPHs and their UFs suggested that they
could be potential bioactive ingredients for use in the formulation of functional
foods as well as natural antioxidants in lipid food systems.
PMID- 28407954
TI - Total determination of chloramphenicol residues in foods by liquid chromatography
tandem mass spectrometry.
AB - A simple and sensitive analytical method for the determination of chloramphenicol
(CAP) and chloramphenicol glucuronide (CAPG) residues in foods such as livestock
products, seafood, honey and royal jelly was developed. The method comprises
solvent extraction with methanol, enzymatic hydrolysis with beta-glucuronidase
and clean-up using a hydrophilic lipophilic balanced copolymer solid phase
extraction column. To determine the optimal conditions for the complete enzymatic
hydrolysis of CAPG, we examined the effect of enzyme concentration and incubation
time on the hydrolysis. The detection of CAP using LC-MS/MS was optimized and
determined by SRM. The developed method was validated using ten food products at
a spiked level of 0.5MUg/kg. The validation results show excellent recoveries (79
109%) and precision (<15%) for CAP and CAPG. The limit of quantification
(S/N>=10) of the developed method was 0.5MUg/kg. The proposed method would be
useful for the regulatory monitoring of CAP and CAPG residues in foods.
PMID- 28407955
TI - Influence of ripeness and maceration of the grapes on levels of furan and
carbonyl compounds in wine - Simultaneous quantitative determination and
assessment of the exposure risk to these compounds.
AB - The validated method based on the use of headspace solid phase microextraction
(HS-SPME) coupled with the comprehensive two-dimensional gas chromatography with
time-of-flight mass spectrometric detection (GC*GC/TOFMS) proved to be
appropriate for this first simultaneous quantitative determination of six toxic
compounds (formaldehyde, acetaldehyde, ethyl carbamate, furan, furfural and
acrolein) found in wines. Acetaldehyde and acrolein coeluted with other wine
compounds, which indicated that difficulties could arise if only one-dimensional
gas chromatography was used for the determination of these compounds. The
advancement of the ripeness degree and increasing the grape maceration time seems
to result in higher concentrations of toxic compounds. The exposure to furan,
acrolein and ethyl carbamate through wine consumption may pose risks to consumer
health, since calculated MOE values were lower than 10,000.
PMID- 28407956
TI - Kinetic stability and membrane structure of liposomes during in vitro infant
intestinal digestion: Effect of cholesterol and lactoferrin.
AB - The effects of cholesterol and lactoferrin on the kinetic stability and membrane
structural integrity of negatively charged liposomes under in vitro infant
intestinal digestion conditions were elucidated using dynamic light scattering,
pH-stat titration, Fourier transform infrared spectroscopy, and pyrene steady
state fluorescence probes. The liposomes had a smaller particle diameter, a wider
size distribution, and a greater negative charge after digestion. The
incorporation of cholesterol into the phospholipid bilayers resulted in a more
ordered conformation in the aliphatic tail region and reduced micropolarity,
indicating that cholesterol can improve the structural stability of liposomal
membranes against intestinal environmental stress. Lactoferrin coverage
facilitated the release of free fatty acids and increased the microfluidity of
the bilayers, reducing the structural integrity of the liposomes. This study
provides useful information on the design of liposomes and other microcapsules
with improved and controlled release properties during digestion for particular
groups of people.
PMID- 28407957
TI - Rapid determination of cholesterol oxidation products in milk powder based
products by reversed phase SPE and HPLC-APCI-MS/MS.
AB - A rapid and sensitive HPLC-APCI-MS/MS method for the determination of cholesterol
oxidation products (COPs) in milk powder based foods is reported. The method
consists in the direct saponification of the sample and purification of
oxysterols by reversed phase C18-SPE followed by HPLC-MS/MS analysis. By this
procedure, the extraction and enrichment of oxysterols are combined in a unique
step, reducing sample manipulation and the possible formation of artifacts. LOD
and LOQ were in the concentration ranges of 2-8ngg-1 and 8-30ngg-1, respectively.
The precision (CV%) was in the range 10-36% in fresh samples with a total COPs
amount from 212 to 645ngg-1 and 6-14% for an oxidized sample with a higher amount
(3651ngg-1). The recovery ranged from 74+/-8% for 7-ketocholesterol to 101+/-12%
for 7alpha-hydroxycholesterol at 200ngg-1 and from 82+/-2% for 7-ketocholesterol
to 117+/-10% for 5alpha,6alpha-epoxycholesterol at 500ngg-1 spiked levels,
respectively.
PMID- 28407958
TI - Drying process of pullulan edible films forming solutions studied by low-field
NMR.
AB - The dynamics of water in pullulan film-forming solutions during drying were
investigated by low-field nuclear magnetic resonance. At the begin of drying, two
transverse relaxation times (T2) at around 32.77 and 2149ms were attributed to
bound and free waters in pullulan samples, respectively. An additional T2 value,
ascribed to the tightly bound water in entanglement zones of pullulan chains,
appeared at around 3.51ms as the drying process continued (beyond 1080min of
drying time). The observed three relaxation times revealed the multi-exponential
relaxation behavior of water in pullulan. Moreover, the polymer exhibited spatial
heterogeneity with increasing drying time from 1200 to 1920min. On the basis of
diffusive and chemical exchange model, the dimension range of pullulan network
decreased from 7.69-32.66 to 4.73-18.14um as the pullulan films solidified.
Furthermore, the rate of chemical exchange between water and pullulan
significantly increased at the later stage of drying process.
PMID- 28407959
TI - Identification of phenolic compounds and biologically related activities from
Ocotea odorifera aqueous extract leaves.
AB - Ocotea odorifera (Vell.) Rohwer is popularly used as food and flavoring. The aim
of this study was to determine the chemical composition of the aqueous extract
from O. odorifera leaves and evaluate the correlation of their phytochemical
composition and biological activities. The antioxidant effect was determined by
DPPH radical scavenging, beta-carotene-linoleic acid and lipid peroxidation
assays; the antibacterial activity was evaluated by the hole plate and MIC
techniques and the antimutagenic activity was evaluated by the Ames test.
Identification of phytochemicals was performed by LC-ESI/MS and the correlation
between the phytochemical composition of the extract and the evaluated
activities. The results allowed the identification of 13 phenolic compounds in
the extract that exhibited high antioxidant activity and moderate antibacterial
and antimutagenic action. Statistical analyses showed correlation of the total
phenolic content with biologically related activities. The phytochemical
analyses, together with the biological results, support the popular use of O.
odorifera.
PMID- 28407960
TI - Contributions of molecular size, charge distribution, and specific amino acids to
the iron-binding capacity of sea cucumber (Stichopus japonicus) ovum
hydrolysates.
AB - This study investigated the contributions of molecular size, charge distribution
and specific amino acids to the iron-binding capacity of sea cucumber (Stichopus
japonicus) ovum hydrolysates (SCOHs), and further explored their iron-binding
sites. It was demonstrated that enzyme type and degree of hydrolysis (DH)
significantly influenced the iron-binding capacity of the SCOHs. The SCOHs
produced by alcalase at a DH of 25.9% possessed the highest iron-binding capacity
at 92.1%. As the hydrolysis time increased, the molecular size of the SCOHs
decreased, the negative charges increased, and the hydrophilic amino acids were
exposed to the surface, facilitating iron binding. Furthermore, the Fourier
transform infrared spectra, combined with amino acid composition analysis,
revealed that iron bound to the SCOHs primarily through interactions with
carboxyl oxygen of Asp, guanidine nitrogen of Arg or nitrogen atoms in imidazole
group of His. The formed SCOHs-iron complexes exhibited a fold and crystal
structure with spherical particles.
PMID- 28407961
TI - Bionic multi-tentacled ionic liquid-modified silica gel for adsorption and
separation of polyphenols from green tea (Camellia sinensis) leaves.
AB - For the first time, a new kind of bionic multi-tentacled ionic liquid-modified
silica gel was synthesized and used as selective adsorbent in the preparative
separation of tea polyphenols (TP) from green tea leaves. It was found that
silica particles with polyvinyl alcohol chains modified by N-methyl imidazole
proline salt (PVA.Im+.Pro-@SiO2) had the excellent performance in selective
adsorption as well as fine separation for target compounds. The new adsorbent
exhibited high adsorption capacity and good reusability, meanwhile the
antioxidant activity of TP could be improved through its efficient enrichment. It
properties and adsorption mechanism were also investigated comprehensively and
compared with those reported sorbents. Finally, the preparative separation of
individual catechin from crude extracts was successfully achieved on the
chromatographic column packed with PVA.Im+.Pro-@SiO2 particles and four main
constituents were obtained successively. The study was expected to provide a new
way for the effective separation of similar bioactive compounds.
PMID- 28407962
TI - Evaluation of bioactive flavonoids and antioxidant activity in Pericarpium Citri
Reticulatae (Citrus reticulata 'Chachi') during storage.
AB - A simple and accurate method using high performance liquid chromatography (HPLC)
with dual wavelength detection was developed to simultaneously determine the
contents of one flavanone glycoside (hesperidin) and five polymethoxylated
flavones (PMFs: sinensetin, 4',5,7,8-tetramethoxyflavone, nobiletin, tangeretin
and 5-O-desmethyl nobiletin) in Pericarpium Citri Reticulatae (Citrus reticulata
'Chachi') ('Chachi' PCR). By modifying the mobile phase compositions and
detection wavelengths, an optimal HPLC condition was obtained, under which the
calibration curves of all six compounds exhibited good linearity (R2>0.99). For
all the tested compounds, the relative standard deviation (RSD) was less than 4%,
and the accuracy ranged from 97.58 to 103.2%. The developed method was
successfully applied to monitor the changes in the contents of six flavonoids in
'Chachi' PCR during storage at 25 degrees C, over a three year period. Color
parameters and antioxidant capacity were also determined to evaluate the sample
quality. The contents of hesperidin decreased while all the polymethoxylated
flavones and antioxidant activities increased throughout the storage period,
demonstrating that polymethoxylated flavones could be used as indices for the
quality change of Chachi' PCR during storage. The results from this study suggest
that the longer storage periods increased the quality of PCR.
PMID- 28407963
TI - An improved method for extraction of nutraceutically important polyphenolics from
Berberis jaeschkeana C.K. Schneid. fruits.
AB - Berberis jaeschkeana fruits, source of nutraceutically important polyphenolics
were investigated. A total of 32 experimental run were conducted under Plackett
Burman and central composite design. Microwave power, methanol and HCl
concentration significantly (p<0.05) affect extraction of polyphenols under
linear, quadratic and interactive effect. The model showed good fitness with
significant (p<0.05) model F-value and a non-significant lack of fit. Under
optimum microwave assisted extraction (MAE) condition the total phenolics,
flavonoids, tannins and antioxidant activity were in closed context with
predicted values. As compared to ultrasonic (UAE) and maceration extraction (ME),
MAE showed significantly (p<0.05) higher recovery of TP, TF and FRAP antioxidant
activity. HPLC-DAD analysis detects a total of 10 polyphenolic compounds under
MAE as compared to 9 under UAE and ME. Designing of MAE conditions showed
promising results for polyphenolic antioxidants extraction as revealed by higher
yield with lesser time and solvent consumption, which can contribute in green
extraction technology and its application in nutraceutical industry.
PMID- 28407964
TI - Dispersive liquid-liquid microextraction coupled with digital image colorimetric
analysis for detection of total iron in water and food samples.
AB - A simple and low cost assay for total iron in various samples based on dispersive
liquid-liquid microextraction (DLLME) coupled with digital scanning image
analysis was proposed. Orthogonal experiment design was utilized to optimize the
amount of extraction solvent and disperser solvent, O-phenanthroline
concentration and buffer pH. Under the optimum conditions, the calibration curve
was linear over the range of 0.047-1.0MUgmL-1 (R2>0.99) of iron. The limit of
detection (LOD) for iron was 14.1MUgL-1 and limit of quantification (LOQ) was
46.5MUgL-1. The relative standard deviations for seven replicate determinations
of 0.5MUgmL-1 of iron was 3.75%. The method was successfully applied for analysis
of total iron in water and food samples without using any spectral instrument and
it could have a potential industrial impact in developing fast and portable
devices to analyze the iron content in water and certain foods.
PMID- 28407965
TI - Highly sensitive fluorescence sensing of zearalenone using a novel aptasensor
based on upconverting nanoparticles.
AB - A facile strategy was successfully developed for the detection of zearalenone
(ZEN). In this assay, highly fluorescent upconversion nanoparticles were
synthesized and conjugated with the complementary oligonucleotide of ZEN aptamer
for use as signal probes. Magnetic nanoparticles immobilized with the ZEN aptamer
were assigned as capture probes. The results exhibited that the linear
correlation between the decreased luminescence intensity of the signal and the
concentration of ZEN was very strong (R2=0.9957) in the range of 0.05-100MUg/L.
In addition, the limit of detection of the proposed method (0.126MUg/kg for corn
and 0.007MUg/L for beer) was significantly lower than the existing methods.
Furthermore, the reliability of the competitive immunoassay format was validated
by comparing the results determined in real food samples to those obtained from a
commercially available method. Overall, the novel aptasensor have showed great
potential for rapid and accurate ZEN determination.
PMID- 28407966
TI - Detection of several common adulterants in raw milk by MID-infrared spectroscopy
and one-class and multi-class multivariate strategies.
AB - A sequential strategy was proposed to detect adulterants in milk using a mid
infrared spectroscopy and soft independent modelling of class analogy technique.
Models were set with low target levels of adulterations including formaldehyde
(0.074g.L-1), hydrogen peroxide (21.0g.L-1), bicarbonate (4.0g.L-1), carbonate
(4.0g.L-1), chloride (5.0g.L-1), citrate (6.5g.L-1), hydroxide (4.0g.L-1),
hypochlorite (0.2g.L-1), starch (5.0g.L-1), sucrose (5.4g.L-1) and water (150g.L
1). In the first step, a one-class model was developed with unadulterated
samples, providing 93.1% sensitivity. Four poorly assigned adulterants were
discarded for the following step (multi-class modelling). Then, in the second
step, a multi-class model, which considered unadulterated and formaldehyde-,
hydrogen peroxide-, citrate-, hydroxide- and starch-adulterated samples was
implemented, providing 82% correct classifications, 17% inconclusive
classifications and 1% misclassifications. The proposed strategy was considered
efficient as a screening approach since it would reduce the number of samples
subjected to confirmatory analysis, time, costs and errors.
PMID- 28407967
TI - Molecular characterization of an unauthorized genetically modified Bacillus
subtilis production strain identified in a vitamin B2 feed additive.
AB - Many food and feed additives result from fermentation of genetically modified
(GM) microorganisms. For vitamin B2 (riboflavin), GM Bacillus subtilis production
strains have been developed and are often used. The presence of neither the GM
strain nor its recombinant DNA is allowed for fermentation products placed on the
EU market as food or feed additive. A vitamin B2 product (80% feed grade)
imported from China was analysed. Viable B. subtilis cells were identified and
DNAs of two bacterial isolates (LHL and LGL) were subjected to three whole genome
sequencing (WGS) runs with different devices (MiSeq, 454 or HiSeq system). WGS
data revealed the integration of a chloramphenicol resistance gene, the deletion
of the endogenous riboflavin (rib) operon and presence of four putative plasmids
harbouring rib operons. Event- and construct-specific real-time PCR methods for
detection of the GM strain and its putative plasmids in food and feed products
have been developed.
PMID- 28407968
TI - Novel nanoliposomal encapsulated omega-3 fatty acids and their applications in
food.
AB - The aim of the present research was to evaluate the application, stability and
suitability of omega3 polyunsaturated fatty acids (PUFAs) incorporated
nanoliposomes in food enrichment. Nanoliposomal omega3 PUFAs was prepared by
Mozafari method, and their application in bread and milk was compared with
unencapsulated (fish oil) and microencapsulated omega3 PUFAs. Sensory evaluation
was conducted to determine the perceptible sensory difference/similarity between
control, unencapsulated, microencapsulated, and nanoliposomal omega3 PUFAs
enriched foods. Results showed no significant (p=0.11) detectable difference
between control and nanoliposomal omega3 PUFAs enriched samples while, samples
enriched with unencapsulated or microencapsulated omega3 PUFAs showed significant
(p=0.02) fishy flavor. Moreover, significantly (p<0.01) higher omega3 PUFAs %
recovery and lower peroxide and anisidine values were observed in nanoliposomal
omega3 PUFAs enriched samples in comparison with other samples. In conclusion, an
effective and reproducible method for application of omega3 PUFAs in the food
system was developed.
PMID- 28407969
TI - The influence of pre-fermentative maceration and ageing factors on ester profile
and marker determination of Pedro Ximenez sparkling wines.
AB - The influence of pre-fermentative maceration and ageing factors on the ester
profiles of Pedro Ximenez sparkling wines was evaluated. The pre-fermentative
maceration consisted of the skin-maceration of musts at 10 degrees C for 6h. The
sparkling wines were produced following the Champenoise method. Samples were
monitored at 3, 6 and 9months of ageing on lees. Sparkling wines with pre
fermentative maceration displayed higher contents of ethyl esters of branched
acids and cinnamates. Meanwhile, those without maceration showed higher levels of
ethyl esters of fatty acids and higher alcohol acetates. The study of statistical
interactions elucidated different hydrolytic kinetics and developments in higher
alcohol acetates and ethyl esters of branched acids during ageing. The
application of a dual criterion based on univariate (ANOVA) and multivariate
analyses (OPLS-DA) allowed us to identify new potential volatile markers related
to pre-fermentative maceration and ageing time, reported for the first time in
sparkling wines.
PMID- 28407970
TI - A simple and rapid method of isolation of active polypeptide complex, yolkin,
from chicken egg yolk.
AB - A large number of bioactive peptides isolated from natural sources are known to
play important physiological roles in the human body. It is possible to use these
as alternative therapy agents. One example is yolkin which can be useful as a
food supplement, a natural therapeutic agent for preventing and treating
cognitive disorders of various origins, preferably in patients with
unsatisfactory responses to known therapies. A new simple method of isolation of
yolkin based on precipitation with ethanol or acetone was developed. The best
precipitation efficiency of both ethanol and acetone was achieved when stirred
into the starting material to a final concentration of 70%. These methods
preserved the ability of yolkin to stimulate human whole blood cells to release
anti-inflammatory cytokines and neurotrophins. At first we indicated that yolkin
displayed a potential neuroprotective effect by the ability to stimulate cells to
produce pro-survival brain derived neurotrophic factor (BDNF).
PMID- 28407971
TI - Effect of phytosanitary irradiation on the postharvest quality of Seedless Kishu
mandarins (Citrus kinokuni mukakukishu).
AB - Transnational trade of 'Seedless Kishu' mandarins (Citrus kinokuni mukakukishu)
would require them to be subjected to a suitable phytosanitary treatment.
Irradiation is used as an effective treatment for many fruit, but the effect on
quality of kishu mandarins is unknown. 'Seedless Kishu' mandarins were treated
with gamma irradiation (150, 400, and 1000Gy) and stored for three weeks at 6
degrees C and then for one week at 20 degrees C. Irradiation at 400 and 1000Gy
promoted browning of the calyx end and fungal infection. Irradiation caused
immediate reductions in pulp firmness, vitamin E, individual sugars and
carotenoids but increased the content of organic acids, except ascorbic acid, and
phenolic compounds. The volatile profile of tested fruit was also differentially
altered by irradiation. Most of these initial changes were dose dependent.
'Seedless Kishu' mandarins are significantly sensitive to irradiation and are not
suitable for treatment at the studied doses.
PMID- 28407972
TI - Determination of aflatoxin M1 in milk samples by means of an inductively coupled
plasma mass spectrometry-based immunoassay.
AB - An inductively coupled plasma mass spectrometry (ICP-MS)-based immunoassay has
been developed to quantify aflatoxin M1 (AFM1) at ultra-trace levels in milk
samples. AFM1 detection is carried out by means of a competitive immunoassay
using secondary biotinylated antibodies and streptavidin-conjugated Au
nanoparticles. After acid addition, nanoparticles are decomposed and Au signal is
registered by means of ICP-MS. Results demonstrate that, under optimum
conditions, the limit of detection of the immunoassay (0.005MUgkg-1) is low
enough to quantify AFM1 according to current international policies (including
the more restrictive European one). Method accuracy and precision was checked by
analyzing an AFM1 certified reference material and different milk samples spiked
with known amounts of AFM1. AFM1 recovery values range from 80% to 102% whereas
inter-assay and intra-assay precision are lower than 15%. Finally, this
immunoassay methodology affords a higher dynamic working range (0.012-2.5MUgkg-1)
than other immunoassay methodologies described in the literature.
PMID- 28407973
TI - Occurrence of deoxynivalenol and deoxynivalenol-3-glucoside in durum wheat from
Argentina.
AB - The occurrence of deoxynivalenol, 3- and 15-deoxynivalenol and deoxynivalenol-3
glucoside in 84 durum wheat samples, from the Argentinean main growing area, was
investigated during 2012/13 and 2013/14 using LC-MS/MS. Deoxynivalenol was found
in all samples at concentrations varying between =5 years) from 2 different hospitals in Pune, India.
The University of Washington Quality of Life Questionnaire was used to measure
QOL and was administered through face-to-face interviews. Various QOL domains
were analyzed by using one-way analysis of variance and Bonferroni adjustments
for post hoc comparisons. RESULTS: Cases had significantly lower scores across
all domains of QOL compared with controls. Overall, the most affected domains
were anxiety and mood. Cancer site significantly influenced QOL, with patients
with cancers of the oropharynx and hypopharynx having the worst mean scores
across all domains. Patients with stage IV cancer had the worst mean scores
across the majority of the QOL domains. Our findings highlight the complex
interactions between individual and clinical predictors that have an impact on
QOL. CONCLUSIONS: QOL needs to be incorporated as an important outcome measure in
an individualized approach to therapeutic and palliative care planning to enable
a better quality of survival of patients with UADT cancers.
PMID- 28407984
TI - Review: allergic contact stomatitis.
AB - Allergic contact stomatitis (ACS) is an oral mucosal immunoinflammatory disorder
variably characterized clinically by erythematous plaques, vesiculation,
ulceration, and/or hyperkeratosis and by pain, burning sensation, or itchiness.
ACS is brought about by a T cell-mediated, delayed hypersensitivity immune
reaction generated by a second or subsequent contact exposure of an allergen with
the oral mucosa, in a genetically susceptible, sensitized subject. Lichenoid
contact reaction is a variant of ACS brought about by direct contact with the
oral mucosa of certain metals in dental restorations. The features of ACS are
neither clinically nor histopathologically specific, so the diagnosis is usually
presumptive and can only be confirmed by resolution of the inflammation after
withdrawal or removal of the suspected causative allergen. When ACS is suspected
but an allergen cannot be identified, patch testing is necessary. In persistent
cases, topical corticosteroids are the treatment of choice, but for severe and
extensive lesions, systemic corticosteroid and systemic antihistamines may be
indicated. In this short review, we highlight the clinical, immunologic, and
histopathological features of ACS, and provide some guidelines for diagnosis and
management.
PMID- 28407985
TI - Histologic variation in high grade oral epithelial dysplasia when associated with
high-risk human papillomavirus.
AB - OBJECTIVES: Reported cytologic alterations associated with high-risk human
papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further
characterization. STUDY DESIGN: Archival cases of high-grade oral epithelial
dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the
average number of mitotic, karyorrhectic, and apoptotic cells per high-power
field. Three groups were then generated on the basis of increasing CS: Focal
(group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12).
Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were
performed. RESULTS: HR-HPV was found significantly more in group 3 (83.3%)
compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P =
.047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the
tongue or the floor of mouth was associated with all groups (P = .04). Increasing
CS was associated with a slightly younger age (P = .04) and increased expression
of p16 (P = .005). CS and p16 expression were not sensitive but were highly
specific predictors for HR-HPV presence. Based on limited follow-up information,
HPV-OED does not differ in clinical aggressiveness compared with conventional
OED. CONCLUSIONS: Increased CS in hgOED is strongly associated with HR-HPV
(mostly HPV16) and p16 expression. CS and p16 expression are specific predictors
of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED
are needed.
PMID- 28407986
TI - Intravenous bisphosphonate therapy does not thicken cementum or change
periodontal ligaments of cancer patients.
AB - OBJECTIVE: To test the hypothesis that intravenous (IV) bisphosphonate (BP)
therapy thickens or alters the micromorphology of cementum and periodontal
ligament (PDL) in cancer patients. STUDY DESIGN: Thirty-two teeth extracted from
24 cancer patients and separated into test (patients who have undergone IV BP
therapy, n = 16) and control (patients naive to BP therapy, n = 16) groups were
studied. Cementum thickness was measured in 3 different areas of the dental root
with polarized light microscopy. PDL was assessed by optical light microscopy and
the immunohistochemical expression of periostin. RESULTS: No significant
difference was detected in cementum thickness (apical, P = .06; medium, P = .16;
cervical, P = .18) between groups. The numbers of fibroblasts in PDL (P = .56),
incremental lines of cementum (P = .51) and the immunohistochemical patterns of
periostin expression in PDL (P = .68) did not differ between groups. CONCLUSION:
IV BP therapy does not thicken cementum or change the micromorphology of PDL.
PMID- 28407987
TI - Topographic analysis of the maxillary premolars relative to the maxillary sinus
and the alveolar bone using cone beam computed tomography.
AB - OBJECTIVE: The purpose of the present study was to elucidate the anatomic
characteristics of the maxillary premolars for the planning of dental treatment
using cone beam computed tomography (CBCT). STUDY DESIGN: CBCT images were
obtained for 150 maxillary premolars in 68 patients. The internal angle formed by
the long axis of the maxillary premolars and the long axis of the alveolar bone
was evaluated on the cross-sectional images. The vertical relationships between
the maxillary premolars and the maxillary sinus were classified into 5
categories. The bone width and internal angle were compared among the images
classified into the 5 categories. RESULTS: The internal angle was 25.5 +/- 6.9
degrees at the maxillary first premolars. The incidence of Type I in the
maxillary first premolars was 46.7%. In the maxillary second premolars, the
incidence of Type I (14.7%) was significantly lower than the total incidence of
Types II, III, IV, and V (85.3%). Type I had the significantly largest internal
angle (28.0 +/- 7.7 degrees ) among all types for the maxillary first premolars.
CONCLUSION: When considering dental treatment in the maxillary premolars, one
should observe the inclination of the maxillary premolars to the alveolar bone as
well as the position of the inferior wall of the maxillary sinus.
PMID- 28407988
TI - Cone beam computed tomography image optimization to detect root fractures in
endodontically treated teeth: an in vitro (phantom) study.
AB - OBJECTIVES: The aim of this study was to evaluate the effect of an optimization
filter (OF) and voxel size on the accuracy of root fracture detection. STUDY
DESIGN: Half of 40 endodontically treated roots were fractured, and the other
half were left intact. All teeth were randomly placed into 5 bovine ribs. Each
rib was scanned with the Planmeca ProMax 3-D using 4 different settings: 75 MUm
and 100 MUm voxel size with and without an OF. Five reviewers reported if a
fracture was present by using a 5-point scale. Intra-/interobserver agreement,
area under the receiver operative characteristic curve, accuracy, sensitivity,
and false-positive rates were analyzed. RESULTS: High kappa-values indicated
strong intra-/interobserver agreement. There was no significant difference in
fracture detection between any of the evaluated techniques. CONCLUSIONS: Because
of the decreased cost, dose area product, and time required, compared with the
other imaging modalities studied, the high-resolution mode (100 MUm) without an
OF is recommended for root fracture detection in endodontically treated teeth.
PMID- 28407989
TI - Prevalence of calcified carotid artery atheromas on digital panoramic images
among perimenopausal and postmenopausal African American women.
AB - OBJECTIVE: Health care disparities, often of an obscure nature, result in African
American women (AAw) having enhanced risk of adverse cardiovascular events.
Therefore, we sought to determine the prevalence of calcified carotid artery
atheromas (CCAA), a validated risk indicator of these events, on their digital
panoramic images. STUDY DESIGN: Comprehensive electronic medical records and
digital panoramic images of self-identified AAw aged >=45 years treated between
2007 and 2014 were retrieved from a Veterans Affairs Dental Service. Images were
reviewed for CCAA in the cervical bifurcation region, and medical records were
reviewed for atherogenic risk factors: hypertension, diabetes, and dyslipidemia.
RESULTS: The study sample of 171 AAw (mean age 58.2 +/- 8.0 years) evidenced a
24% CCAA positive prevalence rate. In comparison with the CCAA negative group,
those with atheromas were significantly older (61.4 +/- 10.1 vs. 57.2 +/- 7.0),
diabetic, and dyslipidemic. Also observed among the full study sample was
significant concordant increase of CCAA prevalence with age. Among those who were
CCAA positive, there was a significant increased prevalence of dyslipidemia with
age. CONCLUSIONS: Panoramic images of older AAw frequently revealed carotid
atheromas, a risk indicator of generalized atherosclerosis and future adverse
cardiovascular events.
PMID- 28407990
TI - Mandibular movements in older people with rheumatoid arthritis.
AB - OBJECTIVE: The aim of this study was to compare the mandibular movements in older
people with and without temporomandibular disorder (TMD) associated with
rheumatoid arthritis (RA). STUDY DESIGN: Thirty partially or completely
edentulous older adults (65.33 +/- 4.7 years) were assigned to 2 groups: (1) with
RA and TMD and (2) without RA and TMD. Chewing movements of the jaws during
mastication of the test material (Optocal) and the range of mandibular movements
were evaluated by using the JT-3-D kinesiographic device before and after new
removable prosthesis insertion. Multiple comparisons were made with analysis of
variance (ANOVA) and the Tukey-Kramer test. RESULTS: Comparisons between the 2
groups before and after new prosthesis insertion revealed that the RA and TMD
group had reduced opening angles (P < .05) during chewing. After insertion of new
prostheses, both groups showed increased opening and closing angles during
chewing (P < .05). The mandibular range of motion results showed that patients
with RA and TMD exhibited lower aperture and laterality movements (P < .05)
compared with controls before and after new prosthesis insertion. However, there
was an increase in aperture, lefty laterality, and protrusion values after new
prosthesis insertion in both groups. CONCLUSIONS: TMD associated with RA may
impair mandibular movements. Well-fitted prostheses may improve mandibular
movements in older adults, especially those with RA.
PMID- 28407991
TI - Three-dimensional volumetric analysis of ghost cell odontogenic carcinoma using 3
D reconstruction software: a case report.
AB - OBJECTIVE: Ghost cell odontogenic carcinoma is a very rare malignant neoplasm.
Tumor volume may be a more precise alternative for determining size, which is
usually measured by maximum linear dimension. The purpose of this case report is
to highlight the importance of obtaining 3-dimensional (3-D) images of the tumor
for volumetric analysis to improve the chances of surgical success. This report
presents a case of ghost cell odontogenic carcinoma infiltrating the maxillary
sinus through the palate. The lesion was surgically treated and subsequently
selected for volumetric reconstruction and analysis of the tumor by using
InVesalius software. In this case report, we describe the use of a pictorial
technique in which the tumor volume was calculated to help predict the surgical
results. RESULTS: The tumor could be visualized in 3-D, with color improving the
image of the segmented volume and thus increasing the perception of boundaries
and depth. CONCLUSIONS: Recognition of the lesion shape by volumetric analysis
can provide the surgical team with clearer information, thereby helping in
surgical planning and consequently increasing the chances of surgical success.
PMID- 28407993
TI - Policies for Use of Real-World Data in Health Technology Assessment (HTA): A
Comparative Study of Six HTA Agencies.
AB - BACKGROUND: Randomized controlled trials provide robust data on the efficacy of
interventions rather than on effectiveness. Health technology assessment (HTA)
agencies worldwide are thus exploring whether real-world data (RWD) may provide
alternative sources of data on effectiveness of interventions. Presently, an
overview of HTA agencies' policies for RWD use in relative effectiveness
assessments (REA) is lacking. OBJECTIVES: To review policies of six European HTA
agencies on RWD use in REA of drugs. A literature review and stakeholder
interviews were conducted to collect information on RWD policies for six
agencies: the Dental and Pharmaceutical Benefits Agency (Sweden), the National
Institute for Health and Care Excellence (United Kingdom), the Institute for
Quality and Efficiency in Healthcare (Germany), the High Authority for Health
(France), the Italian Medicines Agency (Italy), and the National Healthcare
Institute (The Netherlands). The following contexts for RWD use in REA of drugs
were reviewed: initial reimbursement discussions, pharmacoeconomic analyses, and
conditional reimbursement schemes. We identified 13 policy documents and 9
academic publications, and conducted 6 interviews. RESULTS: Policies for RWD use
in REA of drugs notably differed across contexts. Moreover, policies differed
between HTA agencies. Such variations might discourage the use of RWD for HTA.
CONCLUSIONS: To facilitate the use of RWD for HTA across Europe, more alignment
of policies seems necessary. Recent articles and project proposals of the
European network of HTA may provide a starting point to achieve this.
PMID- 28407994
TI - The PMA Scale: A Measure of Physicians' Motivation to Adopt Medical Devices.
AB - BACKGROUND: Studies have often stated that individual-level determinants are
important drivers for the adoption of medical devices. Empirical evidence
supporting this claim is, however, scarce. At the individual level, physicians'
adoption motivation was often considered important in the context of adoption
decisions, but a clear notion of its dimensions and corresponding measurement
scales is not available. OBJECTIVES: To develop and subsequently validate a scale
to measure the motivation to adopt medical devices of hospital-based physicians.
METHODS: The development and validation of the physician-motivation-adoption
(PMA) scale were based on a literature search, internal expert meetings, a pilot
study with physicians, and a three-stage online survey. The data collected in the
online survey were analyzed using exploratory factor analysis (EFA), and the PMA
scale was revised according to the results. Confirmatory factor analysis (CFA)
was conducted to test the results from the EFA in the third stage. Reliability
and validity tests and subgroup analyses were also conducted. RESULTS: Overall,
457 questionnaires were completed by medical personnel of the National Health
Service England. The EFA favored a six-factor solution to appropriately describe
physicians' motivation. The CFA confirmed the results from the EFA. Our tests
indicated good reliability and validity of the PMA scale. CONCLUSIONS: This is
the first reliable and valid scale to measure physicians' adoption motivation.
Future adoption studies assessing the individual level should include the PMA
scale to obtain more information about the role of physicians' motivation in the
broader adoption context.
PMID- 28407995
TI - Impact of a University-Based Outpatient Telemedicine Program on Time Savings,
Travel Costs, and Environmental Pollutants.
AB - OBJECTIVE: The objective of this study was to estimate travel-related and
environmental savings resulting from the use of telemedicine for outpatient
specialty consultations with a university telemedicine program. METHODS: The
study was designed to retrospectively analyze the telemedicine consultation
database at the University of California Davis Health System (UCDHS) between July
1996 and December 2013. Travel distances and travel times were calculated between
the patient home, the telemedicine clinic, and the UCDHS in-person clinic. Travel
cost savings and environmental impact were calculated by determining differences
in mileage reimbursement rate and emissions between those incurred in attending
telemedicine appointments and those that would have been incurred if a visit to
the hub site had been necessary. RESULTS: There were 19,246 consultations
identified among 11,281 unique patients. Telemedicine visits resulted in a total
travel distance savings of 5,345,602 miles, a total travel time savings of
4,708,891 minutes or 8.96 years, and a total direct travel cost savings of
$2,882,056. The mean per-consultation round-trip distance savings were 278 miles,
average travel time savings were 245 minutes, and average cost savings were $156.
Telemedicine consultations resulted in a total emissions savings of 1969 metric
tons of CO2, 50 metric tons of CO, 3.7 metric tons of NOx, and 5.5 metric tons of
volatile organic compounds. CONCLUSIONS: This study demonstrates the positive
impact of a health system's outpatient telemedicine program on patient travel
time, patient travel costs, and environmental pollutants.
PMID- 28407996
TI - A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at
Risk of Hereditary Breast Cancer.
AB - BACKGROUND: The National Comprehensive Cancer Network recommends that women who
carry gene variants that confer substantial risk for breast cancer consider risk
reduction strategies, that is, enhanced surveillance (breast magnetic resonance
imaging and mammography) or prophylactic surgery. Pathogenic variants can be
detected in women with a family history of breast or ovarian cancer syndromes by
multigene panel testing. OBJECTIVES: To investigate whether using a seven-gene
test to identify women who should consider risk-reduction strategies could cost
effectively increase life expectancy. METHODS: We estimated effectiveness and
lifetime costs from a payer perspective for two strategies in two hypothetical
cohorts of women (40-year-old and 50-year-old cohorts) who meet the National
Comprehensive Cancer Network-defined family history criteria for multigene
testing. The two strategies were the usual test strategy for variants in BRCA1
and BRCA2 and the seven-gene test strategy for variants in BRCA1, BRCA2, TP53,
PTEN, CDH1, STK11, and PALB2. Women found to have a pathogenic variant were
assumed to undergo either prophylactic surgery or enhanced surveillance. RESULTS:
The incremental cost-effectiveness ratio for the seven-gene test strategy
compared with the BRCA1/2 test strategy was $42,067 per life-year gained or
$69,920 per quality-adjusted life-year gained for the 50-year-old cohort and
$23,734 per life-year gained or $48,328 per quality-adjusted life-year gained for
the 40-year-old cohort. In probabilistic sensitivity analysis, the seven-gene
test strategy cost less than $100,000 per life-year gained in 95.7% of the trials
for the 50-year-old cohort. CONCLUSIONS: Testing seven breast cancer-associated
genes, followed by risk-reduction management, could cost-effectively improve life
expectancy for women at risk of hereditary breast cancer.
PMID- 28407997
TI - The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical
Rule: Economic Evaluation.
AB - OBJECTIVE: To estimate the cost-effectiveness of a two-step clinical rule using
symptoms, signs and dipstick testing to guide the diagnosis and antibiotic
treatment of urinary tract infection (UTI) in acutely unwell young children
presenting to primary care. METHODS: Decision analytic model synthesising data
from a multicentre, prospective cohort study (DUTY) and the wider literature to
estimate the short-term and lifetime costs and healthcare outcomes (symptomatic
days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies.
We compared GP clinical judgement with three strategies based on a 'coefficient
score' combining seven symptoms and signs independently associated with UTI and
four strategies based on weighted scores according to the presence/absence of
five symptoms and signs. We compared dipstick testing versus laboratory culture
in children at intermediate risk of UTI. RESULTS: Sampling, culture and
antibiotic costs were lowest in high-specificity DUTY strategies (L1.22 and
L1.08) compared to clinical judgement (L1.99). These strategies also
approximately halved urine sampling (4.8% versus 9.1% in clinical judgement)
without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar
across all diagnostic strategies. High-specificity DUTY strategies were more cost
effective than clinical judgement in the short- (iNMB = L0.78 and L0.84) and long
term (iNMB =L2.31 and L2.50). Dipstick tests had poorer cost-effectiveness than
laboratory culture in children at intermediate risk of UTI (iNMB = L-1.41).
CONCLUSIONS: Compared to GPs' clinical judgement, high specificity clinical rules
from the DUTY study could substantially reduce urine sampling, achieving lower
costs and equivalent patient outcomes. Dipstick testing children for UTI is not
cost-effective.
PMID- 28407999
TI - Cost-Effectiveness of TNF-Blocker Injection Spacing for Patients with Established
Rheumatoid Arthritis in Remission: An Economic Evaluation from the Spacing of TNF
Blocker Injections in Rheumatoid Arthritis Trial.
AB - BACKGROUND: In patients with rheumatoid arthritis in remission, a disease
activity-driven tapering of adalimumab or etanercept relying on progressive
injection spacing has not been shown to be equivalent to a maintenance strategy
at full dose in terms of disease activity in the Spacing of TNF-blocker
injections in Rheumatoid ArthritiS Study (STRASS) trial. OBJECTIVES: To evaluate
the cost-effectiveness of such a spacing strategy based on the data of the STRASS
trial. METHODS: This is a cost-utility analysis of the STRASS trial, a French
multicenter 18-month equivalence randomized open-label controlled trial that
included patients at stable dose for at least 1 year, in remission for at least 6
months. Effectiveness was assessed in quality-adjusted life-years (QALYs). Costs
involved in the study period were assessed from a payer perspective. The
decremental cost-effectiveness ratio (DCER) was calculated in the complete cases
sample (n = 98). Several sensitivity analyses were conducted and the impact of
missing data on DCER estimate was investigated. An acceptability analysis was
performed. RESULTS: In the spacing arm, TNF-blockers were stopped for 34.1% of
the patients, tapered for 43.2%, and maintained at full dose for 18.2%. The
spacing strategy was associated with less QALYs gain (mean difference of -0.158;
95% confidence interval [CI] -0.085 to -0.232) and reduced costs (mean difference
of -?8,440; 95% CI -6,507 to -10,212). The estimated DCER of the spacing strategy
over the maintenance at full dose was ?53,417 saved per QALY lost (95% CI 32,230
to 104,700). CONCLUSIONS: The spacing strategy appears cost-effective, but the
acceptability of such a QALY loss reported to the cost avoided remains to be
evaluated, because no consensual threshold has been determined for willingness to
accept as compared with willingness to pay.
PMID- 28407998
TI - A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women
with Ovarian Cancer.
AB - OBJECTIVES: To evaluate the long-term cost-effectiveness of germline BRCA1 and
BRCA2 (collectively termed "BRCA") testing in women with epithelial ovarian
cancer, and testing for the relevant mutation in first- and second-degree
relatives of BRCA mutation-positive individuals, compared with no testing. Female
BRCA mutation-positive relatives of patients with ovarian cancer could undergo
risk-reducing mastectomy and/or bilateral salpingo-oophorectomy. METHODS: A cost
effectiveness model was developed that included the risks of breast and ovarian
cancer; the costs, utilities, and effects of risk-reducing surgery on cancer
rates; and the costs, utilities, and mortality rates associated with cancer.
RESULTS: BRCA testing of all women with epithelial ovarian cancer each year is
cost-effective at a UK willingness-to-pay threshold of L20,000/quality-adjusted
life-year (QALY) compared with no testing, with an incremental cost-effectiveness
ratio of L4,339/QALY. The result was primarily driven by fewer cases of breast
cancer (142) and ovarian cancer (141) and associated reductions in mortality (77
fewer deaths) in relatives over the subsequent 50 years. Sensitivity analyses
showed that the results were robust to variations in the input parameters.
Probabilistic sensitivity analysis showed that the probability of germline BRCA
mutation testing being cost-effective at a threshold of L20,000/QALY was 99.9%.
CONCLUSIONS: Implementing germline BRCA testing in all patients with ovarian
cancer would be cost-effective in the United Kingdom. The consequent reduction in
future cases of breast and ovarian cancer in relatives of mutation-positive
individuals would ease the burden of cancer treatments in subsequent years and
result in significantly better outcomes and reduced mortality rates for these
individuals.
PMID- 28408000
TI - Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer
in the Canadian Health Care System.
AB - OBJECTIVES: To assess the cost-effectiveness of gemcitabine (G), G + 5
fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G
+ nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic
cancer from a Canadian public health payer's perspective, using data from a
recently published Bayesian network meta-analysis. METHODS: Analysis was
conducted through a three-state Markov model and used data on the progression of
disease with treatment from the gemcitabine arms of randomized controlled trials
combined with estimates from the network meta-analysis for the newer regimens.
Estimates of health care costs were obtained from local providers, and utilities
were derived from the literature. The model estimates the effect of treatment
regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per
annum. RESULTS: At a willingness-to-pay (WTP) threshold of greater than $30,666
per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of
$50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%.
There was no price reduction for nab-paclitaxel when GnP was optimal.
CONCLUSIONS: From a Canadian public health payer's perspective at the present
time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost
effectiveness criterion. GnP is not cost-effective regardless of the WTP
threshold.
PMID- 28408001
TI - Cost-Effectiveness Analysis of a Skin Awareness Intervention for Early Detection
of Skin Cancer Targeting Men Older Than 50 Years.
AB - OBJECTIVES: To assess the cost-effectiveness of an educational intervention
encouraging self-skin examinations for early detection of skin cancers among men
older than 50 years. METHODS: A lifetime Markov model was constructed to combine
data from the Skin Awareness Trial and other published sources. The model
incorporated a health system perspective and the cost and health outcomes for
melanoma, squamous and basal cell carcinomas, and benign skin lesions. Key model
outcomes included Australian costs (2015), quality-adjusted life-years (QALYs),
life-years, and counts of skin cancers. Univariate and probabilistic sensitivity
analyses were undertaken to address parameter uncertainty. RESULTS: The mean cost
of the intervention was A$5,298 compared with A$4,684 for usual care, whereas
mean QALYs were 7.58 for the intervention group and 7.77 for the usual care
group. The intervention was thus inferior to usual care. When only survival gain
is considered, the model predicted the intervention would cost A$1,059 per life
year saved. The likelihood that the intervention was cost-effective up to
A$50,000 per QALY gained was 43.9%. The model was stable to most data estimates;
nevertheless, it relies on the specificity of clinical diagnosis of skin cancers
and is subject to limited health utility data for people with skin lesions.
CONCLUSIONS: Although the intervention improved skin checking behaviors and
encouraged men to seek medical advice about suspicious lesions, the overall costs
and effects from also detecting more squamous and basal cell carcinomas and
benign lesions outweighed the positive health gains from detecting more thin
melanomas.
PMID- 28408002
TI - Economic Burden of Attention-Deficit/Hyperactivity Disorder among Pediatric
Patients in the United States.
AB - OBJECTIVES: To determine the adjusted incremental total costs (direct and
indirect) for patients (aged 3-17 years) with attention-deficit/hyperactivity
disorder (ADHD) and the differences in the adjusted incremental direct
expenditures with respect to age groups (preschoolers, 0-5 years; children, 6-11
years; and adolescents, 12-17 years). METHODS: The 2011 Medical Expenditure Panel
Survey was used as the data source. The ADHD cohort consisted of patients aged 0
to 17 years with a diagnosis of ADHD, whereas the non-ADHD cohort consisted of
subjects in the same age range without a diagnosis of ADHD. The annual
incremental total cost of ADHD is composed of the incremental direct expenditures
and indirect costs. A two-part model with a logistic regression (first part) and
a generalized linear model (second part) was used to estimate the incremental
costs of ADHD while controlling for patient characteristics and access-to-care
variables. RESULTS: The 2011 Medical Expenditure Panel Survey database included
9108 individuals aged 0 to 17 years, with 458 (5.0%) having an ADHD diagnosis.
The ADHD cohort was 4.90 times more likely (95% confidence interval [CI] 2.97
8.08; P < 0.001) than the non-ADHD cohort to have an expenditure of at least $1,
and among those with positive expenditures, the ADHD cohort had 58.4% higher
expenditures than the non-ADHD cohort (P < 0.001). The estimated adjusted annual
total incremental cost of ADHD was $949.24 (95% CI $593.30-$1305.18; P < 0.001).
The adjusted annual incremental total direct expenditure for ADHD was higher
among preschoolers ($989.34; 95% CI $402.70-$1575.98; P = 0.001) than among
adolescents ($894.94; 95% CI $428.16-$1361.71; P < 0.001) or children ($682.71;
95% CI $347.94-$1017.48; P < 0.001). CONCLUSIONS: Early diagnosis and use of
evidence-based treatments may address the substantial burden of ADHD.
PMID- 28408003
TI - Evaluation of Noncompletion Bias and Long-Term Adherence in a 10-Year Patient
Reported Outcome Monitoring Program in Clinical Routine.
AB - BACKGROUND: Currently there is little knowledge on real-life sustainability of
routine patient-reported outcome (PRO) measurement and the representativeness of
collected data. OBJECTIVES: The investigation of routine PRO with regard to
noncompletion bias and long-term adher- ence, considering the potential impact of
mode of assessment (MOA) (paper-pencil vs. electronic PRO [ePRO]) and patient
characteristics. METHODS: At our department, routine PRO measurement in
oncological patients is being done since 2005 using different MOA (paper-pencil
assessment until 2011 and ePRO assessment from 2011 onward). We analyzed two
different patient groups: patients eligible in both periods (both-MOA group) and
patients eligible in only one period (one-MOA group). The primary outcome was PRO
noncompletion (100% missing questionnaires). The secondary outcome was poor PRO
adherence (>20% missing questionnaires). Multivariate logistic regression models
were developed, testing the impact of MOA and patient characteristics on the
outcomes in the different patient groups. RESULTS: Data from 1484 eligible
patients were included in the analyses. Most of the patients could be included in
PRO assessment at least once. PRO noncompletion rates were clearly higher during
paper-pencil assessment (odds ratios between 2.72 and 4.31), as were poor PRO
adherence rates (odd ratio 2.23). Analyses of potential bias by patient
characteristics showed that male patients had a higher risk of poor adherence.
Other factors with significant impact were age, country, and cancer diagnosis,
but results were indecisive. CONCLUSIONS: ePRO increased the feasibility of our
clinical routine PRO data for retrospective analyses by increasing completion
rates. In general, potential completion bias regarding certain patient
characteristics requires attention before generalizing results to the respective
populations.
PMID- 28408004
TI - Development of the Diary for Irritable Bowel Syndrome Symptoms to Assess
Treatment Benefit in Clinical Trials: Foundational Qualitative Research.
AB - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder
characterized by abdominal pain and alterations in bowel habits. Three subtypes
are defined on the basis of stool patterns: diarrhea-predominant IBS,
constipation-predominant IBS, and alternating or mixed IBS. OBJECTIVES: To
develop patient-reported outcome measures for qualification by the Food and Drug
Administration to support product approvals and labeling in IBS; the article
focuses on the qualitative research that provided the foundation for the new
measures. METHODS: Forty-nine concept elicitation and 42 cognitive debriefing
interviews were conducted with subjects meeting Rome III criteria; additional
criteria were imposed to yield a sample representative of the target patient
population. RESULTS: Although incomplete bowel movements, abnormal stool
frequency and consistency, and abdominal pain, discomfort, and bloating were
reported most frequently across concept elicitation interviews, the relative
importance of specific symptoms varied by subtype. Among their five symptoms most
important to treat, diarrhea-predominant and alternating or mixed IBS subjects
frequently identified urgency, loose/watery stools, abdominal pain, and cramping,
whereas constipation-predominant IBS subjects commonly included infrequent and
incomplete bowel movements, bloating, and abdominal pain. The cognitive
debriefing interviews facilitated refinement of each item set, supported minor
modifications following translatability assessment, and suggested improvements to
the electronic interface. Furthermore, subjects reported that every item was
relevant and no concepts of importance were missing. CONCLUSIONS: Results support
the content validity of the IBS patient-reported outcome measures. A pilot study
was recently initiated to inform item reduction, develop scoring algorithms, and
provide preliminary psychometric information. Comprehensive psychometric
evaluation and responder definition development will follow.
PMID- 28408005
TI - Balancing the Optimal and the Feasible: A Practical Guide for Setting Up Patient
Registries for the Collection of Real-World Data for Health Care Decision Making
Based on Dutch Experiences.
AB - OBJECTIVES: The aim of this article was to provide practical guidance in setting
up patient registries to facilitate real-world data collection for health care
decision making. METHODS: This guidance was based on our experiences and
involvement in setting up patient registries in oncology in the Netherlands. All
aspects were structured according to 1) mission and goals ("the Why"), 2)
stakeholders and funding ("the Who"), 3) type and content ("the What"), and 4)
identification and recruitment of patients, data handling, and pharmacovigilance
("the How"). RESULTS: The mission of most patient registries is improving patient
health by improving the quality of patient care; monitoring and evaluating
patient care is often the primary goal ("the Why"). It is important to align the
objectives of the registry and agree on a clear and functional governance
structure with all stakeholders ("the Who"). There is often a trade off between
reliability, validity, and specificity of data elements and feasibility of data
collection ("the What"). Patient privacy should be carefully protected, and
address (inter-)national and local regulations. Patient registries can reveal
unique safety information, but it can be challenging to comply with
pharmacovigilance guidelines ("the How"). CONCLUSIONS: It is crucial to set up an
efficient patient registry that serves its aims by collecting the right data of
the right patient in the right way. It can be expected that patient registries
will become the new standard alongside randomized controlled trials due to their
unique value.
PMID- 28408006
TI - A Novel Patient-Derived Conceptual Model of the Impact of Celiac Disease in
Adults: Implications for Patient-Reported Outcome and Health-Related Quality-of
Life Instrument Development.
AB - BACKGROUND: Celiac disease is a chronic inflammatory condition with wide ranging
effects on individual's lives caused by a combination of symptoms and the burden
of adhering to a gluten-free diet (GFD). OBJECTIVES: To further understand
patients' experience of celiac disease, the impact it has on health-related
quality of life (HRQOL), and to develop a conceptual model describing this
impact. METHODS: Adults with celiac disease on a GFD reporting symptoms within
the previous 3 months were included; patients with refractory celiac disease and
confounding medical conditions were excluded. A semistructured discussion guide
was developed exploring celiac disease symptoms and impact on patients' HRQOL. An
experienced interviewer conducted in-depth interviews. The data set was coded and
analyzed using thematic analysis to identify concepts, themes, and the inter
relationships between them. Data saturation was monitored and concepts identified
formed the basis of the conceptual model. RESULTS: Twenty-one participants were
recruited, and 32 distinct gluten-related symptoms were reported and data
saturation was reached. Analysis identified several themes impacting patients'
HRQOL: fears and anxiety, day-to-day management of celiac disease, physical
functioning, sleep, daily activities, social activities, emotional functioning,
and relationships. The conceptual model highlights the main areas of impact and
the relationships between concepts. CONCLUSIONS: Both symptoms and maintaining a
GFD have a substantial impact on patient functioning and HRQOL in adults with
celiac disease. The conceptual model derived from these data may help to design
future patient-reported outcomes as well as interventions to improve the quality
of life in an individual with celiac disease.
PMID- 28408007
TI - Instrument-Defined Estimates of the Minimally Important Difference for EQ-5D-5L
Index Scores.
AB - BACKGROUND: The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) is a
preference-based measure of health-related quality of life (HRQOL), which yields
an index score anchored at 0 (dead) and 1 (full health). We lack evidence on
estimates for the minimally important difference (MID) of the EQ-5D-5L that will
help in interpreting differences or changes in HRQOL measured by this scale
score. OBJECTIVES: To estimate the MID of the EQ-5D-5L index score for available
scoring algorithms including algorithms from Canada, China, Spain, Japan,
England, and Uruguay. METHODS: A simulation-based approach based on instrument
defined single-level transitions was used to estimate the MID values of the EQ-5D
5L for each country-specific scoring algorithm. RESULTS: The simulation-based
instrument-defined MID estimates (mean +/- SD) for each country-specific scoring
algorithm were as follows: Canada, 0.056 +/- 0.011; China, 0.069 +/- 0.007;
Spain, 0.061 +/- 0.008; Japan, 0.048 +/- 0.004; England, 0.063 +/- 0.013; and
Uruguay, 0.063 +/- 0.019. Differences in MID estimates reflect differences in
population preferences, in valuation techniques used, as well as in modeling
strategies. After excluding the maximum-valued scoring parameters, the MID
estimates (mean +/- SD) were as follows: Canada, 0.037 +/- 0.001; China, 0.058 +/
0.005; Spain, 0.045 +/- 0.009; Japan, 0.044 +/- 0.004; England, 0.037 +/- 0.008;
and Uruguay, 0.040 +/- 0.010. CONCLUSIONS: Simulation-based estimates of the MID
of the EQ-5D-5L index score were generally between 0.037 and 0.069, which are
similar to the MID estimates of other preference-based HRQOL measures.
PMID- 28408008
TI - Eliciting Preferences for Information Provision in Newborn Bloodspot Screening
Programs.
AB - BACKGROUND: The national newborn bloodspot screening programs (NBSPs) are
continually expanding to screen for more conditions. OBJECTIVES: To quantify
parents' preferences for information and the way in which this is provided in
example NBSPs. METHODS: A hybrid choice experiment, combining a conjoint analysis
and a discrete choice experiment, was designed. A sample of current and future
parents between the ages of 18 and 45 years was identified via an Internet panel.
Respondents completed one of two survey versions (9 conditions and 20 conditions)
comprising a validated measure of attitudes toward involvement in decision
making, 6 CA questions (11 information attributes), 10 DCE questions (4
attributes: 3 process and the ability to make an informed decision), and
demographic questions. RESULTS: Of the 702 respondents who completed the survey,
58% were women, 48% were between 25 and 34 years old, and 48% were current
parents. All types of information were identified to statistically significantly
improve parents' ability to make a decision. Participants preferred taking an
"active" role in decision making. Respondents to the 9-condition survey preferred
information before 20 weeks (willingness to pay [WTP] L11.88; CI L5.56 to L19.53)
and the 20-condition group after 20 weeks (WTP L15.91; CI L10.64 to L21.63). All
respondents disliked receiving information 3 days after birth, with the 20
condition group also being averse to receiving it on day 5 (WTP -L11.20; CI
L18.40 to 5.72). Respondents in both groups preferred to receive their
information in an individual discussion. CONCLUSIONS: This study suggests that
parents' preferences for receiving NBS information differ from how this
information is given in current UK practice.
PMID- 28408009
TI - Estimating an EQ-5D-5L Value Set for China.
AB - OBJECTIVES: To estimate a five-level EuroQol five-dimensional questionnaire (EQ
5D-5L) value set for China using the health preferences of residents living in
the urban areas of the country. METHODS: The values of a subset of the EQ-5D-5L
defined health states (n = 86) were elicited using the time trade-off (TTO)
technique from a sample of urban residents (n = 1271) recruited from five Chinese
cities. In computer-assisted personal interviews, participants each completed 10
TTO tasks. Two additive and two multiplicative regression models were evaluated
for their performance in describing the relationship between TTO values and
health state characteristics using a cross-validation approach. Final values were
generated using the best-performed model and a rescaling method. RESULTS: The 8-
and 9-parameter multiplicative models unanimously outperformed the 20-parameter
additive model using a random or fixed intercept in predicting values for out-of
sample health states in the cross-validation analysis and their coefficients were
estimated with lower standard errors. The prediction accuracies of the two
multiplicative models measured by the mean absolute error and the intraclass
correlation coefficient were very similar, thus favoring the more parsimonious
model. CONCLUSIONS: The 8-parameter multiplicative model performed the best in
the study and therefore was used to generate the EQ-5D-5L value set for China. We
recommend using rescaled values whereby 1 represents the value of instrument
defined full health in economic evaluation of health technologies in China
whenever the EQ-5D-5L data are available.
PMID- 28408011
TI - Determining Criteria and Weights for Prioritizing Health Technologies Based on
the Preferences of the General Population: A New Zealand Pilot Study.
AB - OBJECTIVES: The use of multicriteria decision analysis for health technology
prioritization depends on decision-making criteria and weights according to their
relative importance. We report on a methodology for determining criteria and
weights that was developed and piloted in New Zealand and enables extensive
participation by members of the general population. METHODS: Stimulated by a
preliminary ranking exercise that involved prioritizing 14 diverse technologies,
six focus groups discussed what matters to people when thinking about
technologies that should be funded. These discussions informed the specification
of criteria related to technologies' benefits for use in a discrete choice survey
designed to generate weights for each individual participant as well as mean
weights. A random sample of 3218 adults was invited to participate. To check test
retest reliability, a subsample completed the survey twice. Cluster analysis was
performed to identify participants with similar patterns of weights. RESULTS: Six
benefits-related criteria were distilled from the focus group discussions and
included in the discrete choice survey, which was completed by 322 adults (10%
response rate). Most participants (85%) found the survey easy to understand, and
the survey exhibited test-retest reliability. The cluster analysis revealed that
participant weights are related more to idiosyncratic personal preferences than
to demographic and background characteristics. CONCLUSIONS: The methodology
enables extensive participation by members of the general population, for whom it
is both acceptable and reliable. Generating weights for each participant allows
the heterogeneity of individual preferences, and the extent to which they are
related to demographic and background characteristics, to be tested.
PMID- 28408010
TI - Be Careful What You Ask For: Effects of Benefit Descriptions on Diabetes
Patients' Benefit-Risk Tradeoff Preferences.
AB - BACKGROUND: As more studies report on patient preferences for diabetes treatment,
identifying diabetes outcomes other than glycated hemoglobin (HbA1c) to describe
effectiveness is warranted to understand patient-relevant, benefit-risk
tradeoffs. OBJECTIVE: The aim of the study was to evaluate how preferences differ
when effectiveness (glycemic control) is presented as long-term sequela (LTS)
risk mitigation rather than an asymptomatic technical marker (HbA1c). METHODS:
People with type 2 diabetes and using insulin (n = 3160) were randomly assigned
to four self-administered, discrete-choice experiments that differed by their
presentation of effectiveness. Epidemiologic reviews were conducted to ensure a
close approximation of LTS risk relative to HbA1c levels. The relative importance
of treatment benefit-risk characteristics and maximum acceptable risk tradeoffs
was estimated using an error-component logit model. Log-likelihood ratio tests
were used to compare parameter vectors. RESULTS: In total, 1031 people responded
to the survey. Significantly more severe hypoglycemic events were accepted for a
health improvement in terms of LTS mitigation versus HbA1c improvement (0.7
events per year; 95% confidence interval [CI]: 0.4-1.0 vs. 0.2 events per year
95% CI: -0.02 to 0.5) and avoidance of treatment-related heart attack risk (1.4
severe hypoglycemic events per year; 95% CI: 0.8-1.9 vs. 1 event per year; 95%
CI: 0.6-1.3). This finding is supported by a log-likelihood test that rejected at
the 0.05 level that respondent preference structures are similar across the
different experimental arms of the discrete-choice experiment. CONCLUSION: We
found evidence that benefit descriptions influence elicited preferences for the
benefit-risk characteristics of injectable diabetes treatment. These findings
argue for using carefully defined effectiveness measures to accurately take
account of the patient perspective in benefit-risk assessments.
PMID- 28408012
TI - Comparing Generic and Condition-Specific Preference-Based Measures in Epilepsy:
EQ-5D-3L and NEWQOL-6D.
AB - BACKGROUND: There is debate about the psychometric characteristics of the three
level EuroQol five-dimensional questionnaire (EQ-5D-3L) for use in epilepsy. In
response to the concerns, an epilepsy-specific preference-based measure (NEWQOL
6D) was developed. The psychometric characteristics of the NEWQOL-6D, however,
have not been assessed. OBJECTIVES: To investigate the validity and
responsiveness of the EQ-5D-3L and the Quality of Life in Newly Diagnosed
Epilepsy Instrument-six dimensions (NEWQOL-6D) for use in the assessment of
treatments for newly diagnosed focal epilepsy. METHODS: The analysis used data
from the Standard And New Antiepileptic Drugs trial including patients with focal
epilepsy. We assessed convergent validity using correlations, and known-group
validity across different epilepsy and general health severity indicators using
analysis of variance and effect sizes. The responsiveness of the measures to
change over time was assessed using standardized response means. We also assessed
agreement between the measures. RESULTS: There was some level of convergence and
agreement between the measures in terms of utility score but divergence in the
concepts measured by the descriptive systems. Both instruments displayed known
group validity, with significant differences between severity groups, and
generally slightly larger effect sizes for the NEWQOL-6D across the epilepsy
specific indicators. Evidence for responsiveness was less clear, with small to
moderate standardized response means demonstrating different levels of change
across different indicators. CONCLUSIONS: There was an overall tendency for the
NEWQOL-6D to better reflect differences across groups, but this does not
translate into large absolute utility differences. Both the EQ-5D-3L and the
NEWQOL-6D show some evidence of validity for providing utility values for
economic evaluations in newly diagnosed focal epilepsy.
PMID- 28408013
TI - Association of Preference-Based Health-Related Quality of Life with Weight Loss
in Obese Adults.
AB - BACKGROUND: The obesity epidemic is linked to substantial health care resource
use, reduction in workforce and home productivity, and poor health-related
quality of life (HRQOL). Changes in body mass index (BMI) are associated with
improvements in HRQOL; the nature of this relationship, however, has not been
reliably described. OBJECTIVES: To determine the independent association between
changes in BMI and change in utility-based HRQOL. METHODS: Data were
prospectively collected on 500 severely obese adult patients enrolled in a single
center obesity management clinic. Univariable and multivariable linear
regressions were performed, adjusting for the effect of the intervention itself,
obesity-related comorbidities, BMI at enrollment, age, and sex. RESULTS: A 1-unit
reduction in BMI was associated with a 0.0075 (95% confidence interval 0.0041
0.0109) increase in the EuroQol five-dimensional questionnaire score. This
relationship was unaltered in various analyses, and is likely applicable to any
health-care-induced changes in BMI. CONCLUSIONS: The quantification of this
association advances the understanding of the clinical benefits of interventions
that affect BMI, and can inform more robust cost-utility analyses.
PMID- 28408014
TI - Cost-Effectiveness Thresholds in Global Health: Taking a Multisectoral
Perspective.
AB - Good health is a function of a range of biological, environmental, behavioral,
and social factors. The consumption of quality health care services is therefore
only a part of how good health is produced. Although few would argue with this,
the economic framework used to allocate resources to optimize population health
is applied in a way that constrains the analyst and the decision maker to health
care services. This approach risks missing two critical issues: 1) multiple
sectors contribute to health gain and 2) the goods and services produced by the
health sector can have multiple benefits besides health. We illustrate how
present cost-effectiveness thresholds could result in health losses, particularly
when considering health-producing interventions in other sectors or public health
interventions with multisectoral outcomes. We then propose a potentially more
optimal second best approach, the so-called cofinancing approach, in which the
health payer could redistribute part of its budget to other sectors, where
specific nonhealth interventions achieved a health gain more efficiently than the
health sector's marginal productivity (opportunity cost). Likewise, other sectors
would determine how much to contribute toward such an intervention, given the
current marginal productivity of their budgets. Further research is certainly
required to test and validate different measurement approaches and to assess the
efficiency gains from cofinancing after deducting the transaction costs that
would come with such cross-sectoral coordination.
PMID- 28408015
TI - Accounting for Cured Patients in Cost-Effectiveness Analysis.
AB - BACKGROUND: Economic evaluations often measure an intervention effect with mean
overall survival (OS). Emerging types of cancer treatments offer the possibility
of being "cured" in that patients can become long-term survivors whose risk of
death is the same as that of a disease-free person. Describing cured and noncured
patients with one shared mean value may provide a biased assessment of a therapy
with a cured proportion. OBJECTIVE: The purpose of this article is to explain how
to incorporate the heterogeneity from cured patients into health economic
evaluation. METHODS: We analyzed clinical trial data from patients with advanced
melanoma treated with ipilimumab (Ipi; n = 137) versus glycoprotein 100 (gp100; n
= 136) with statistical methodology for mixture cure models. Both cured and
noncured patients were subject to background mortality not related to cancer.
RESULTS: When ignoring cured proportions, we found that patients treated with Ipi
had an estimated mean OS that was 8 months longer than that of patients treated
with gp100. Cure model analysis showed that the cured proportion drove this
difference, with 21% cured on Ipi versus 6% cured on gp100. The mean OS among the
noncured cohort patients was 10 and 9 months with Ipi and gp100, respectively.
The mean OS among cured patients was 26 years on both arms. When ignoring cured
proportions, we found that the incremental cost-effectiveness ratio (ICER) when
comparing Ipi with gp100 was $324,000/quality-adjusted life-year (QALY) (95%
confidence interval $254,000-$600,000). With a mixture cure model, the ICER when
comparing Ipi with gp100 was $113,000/QALY (95% confidence interval $101,000
$154,000). CONCLUSIONS: This analysis supports using cure modeling in health
economic evaluation in advanced melanoma. When a proportion of patients may be
long-term survivors, using cure models may reduce bias in OS estimates and
provide more accurate estimates of health economic measures, including QALYs and
ICERs.
PMID- 28408016
TI - A Practical ANOVA Approach for Uncertainty Analysis in Population-Based Disease
Microsimulation Models.
AB - OBJECTIVES: To provide a practical approach for calculating uncertainty intervals
and variance components associated with initial-condition and dynamic-equation
parameters in computationally expensive population-based disease microsimulation
models. METHODS: In the proposed uncertainty analysis approach, we calculated the
required computational time and the number of runs given a user-defined error
bound on the variance of the grand mean. The equations for optimal sample sizes
were derived by minimizing the variance of the grand mean using initial estimates
for variance components. Finally, analysis of variance estimators were used to
calculate unbiased variance estimates. RESULTS: To illustrate the proposed
approach, we performed uncertainty analysis to estimate the uncertainty
associated with total direct cost of osteoarthritis in Canada from 2010 to 2031
according to a previously published population health microsimulation model of
osteoarthritis. We first calculated crude estimates for initial-population
sampling and dynamic-equation parameters uncertainty by performing a small number
of runs. We then calculated the optimal sample sizes and finally derived 95%
uncertainty intervals of the total cost and unbiased estimates for variance
components. According to our results, the contribution of dynamic-equation
parameter uncertainty to the overall variance was higher than that of initial
parameter sampling uncertainty throughout the study period. CONCLUSIONS: The
proposed analysis of variance approach provides the uncertainty intervals for the
mean outcome in addition to unbiased estimates for each source of uncertainty.
The contributions of each source of uncertainty can then be compared with each
other for validation purposes so as to improve the model accuracy.
PMID- 28408017
TI - Systematic Review of Health Economic Impact Evaluations of Risk Prediction
Models: Stop Developing, Start Evaluating.
AB - BACKGROUND: Although health economic evaluations (HEEs) are increasingly common
for therapeutic interventions, they appear to be rare for the use of risk
prediction models (PMs). OBJECTIVES: To evaluate the current state of HEEs of PMs
by performing a comprehensive systematic review. METHODS: Four databases were
searched for HEEs of PM-based strategies. Two reviewers independently selected
eligible articles. A checklist was compiled to score items focusing on general
characteristics of HEEs of PMs, model characteristics and quality of HEEs,
evidence on PMs typically used in the HEEs, and the specific challenges in
performing HEEs of PMs. RESULTS: After screening 791 abstracts, 171 full texts,
and reference checking, 40 eligible HEEs evaluating 60 PMs were identified. In
these HEEs, PM strategies were compared with current practice (n = 32; 80%), to
other stratification methods for patient management (n = 19; 48%), to an extended
PM (n = 9; 23%), or to alternative PMs (n = 5; 13%). The PMs guided decisions on
treatment (n = 42; 70%), further testing (n = 18; 30%), or treatment
prioritization (n = 4; 7%). For 36 (60%) PMs, only a single decision threshold
was evaluated. Costs of risk prediction were ignored for 28 (46%) PMs.
Uncertainty in outcomes was assessed using probabilistic sensitivity analyses in
22 (55%) HEEs. CONCLUSIONS: Despite the huge number of PMs in the medical
literature, HEE of PMs remains rare. In addition, we observed great variety in
their quality and methodology, which may complicate interpretation of HEE results
and implementation of PMs in practice. Guidance on HEE of PMs could encourage and
standardize their application and enhance methodological quality, thereby
improving adequate use of PM strategies.
PMID- 28408019
TI - Non-ST-Segment Elevation Acute Coronary Syndromes: Lessons Learned Over the Last
Decade.
PMID- 28408018
TI - Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute
Coronary Syndrome: The ICTUS Trial.
AB - BACKGROUND: The ICTUS (Invasive Versus Conservative Treatment in Unstable
Coronary Syndromes) trial compared early invasive strategy with a selective
invasive strategy in patients with non-ST-segment elevation acute coronary
syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of
an early invasive strategy was found at 1 and 5 years. OBJECTIVES: The aim of
this study was to determine the 10-year clinical outcomes of an early invasive
strategy versus a selective invasive strategy in patients with NSTE-ACS and an
elevated cardiac troponin T. METHODS: The ICTUS trial was a multicenter,
randomized controlled clinical trial that included 1,200 patients with NSTE-ACS
and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003.
We collected 10-year follow-up of death, myocardial infarction (MI), and
revascularization through the Dutch population registry, patient phone calls,
general practitioners, and hospital records. The primary outcome was the 10-year
composite of death or spontaneous MI. Additional outcomes included the composite
of death or MI, death, MI (spontaneous and procedure-related), and
revascularization. RESULTS: Ten-year death or spontaneous MI was not
statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]:
1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization
occurred in 82.6% of the early invasive group and 60.5% in the selective invasive
group. There were no differences in additional outcomes, except for a higher rate
of death or MI in the early invasive group compared with the rates for the
selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p =
0.009), driven by a higher rate of procedure-related MI in the early invasive
group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001). CONCLUSIONS: In
patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive
strategy has no benefit over a selective invasive strategy in reducing the 10
year composite outcome of death or spontaneous MI, and a selective invasive
strategy may be a viable option in selected patients.
PMID- 28408020
TI - Risk Stratification for Patients in Cardiogenic Shock After Acute Myocardial
Infarction.
AB - BACKGROUND: Mortality in cardiogenic shock (CS) remains high. Early risk
stratification is crucial to make adequate treatment decisions. OBJECTIVES: This
study sought to develop an easy-to-use, readily available risk prediction score
for short-term mortality in patients with CS, derived from the IABP-SHOCK II
(Intraaortic Balloon Pump in Cardiogenic Shock) trial. METHODS: The score was
developed using a stepwise multivariable regression analysis. RESULTS: Six
variables emerged as independent predictors for 30-day mortality and were used as
score parameters: age >73 years, prior stroke, glucose at admission >10.6 mmol/l
(191 mg/dl), creatinine at admission >132.6 MUmol/l (1.5 mg/dl), Thrombolysis In
Myocardial Infarction flow grade <3 after percutaneous coronary intervention, and
arterial blood lactate at admission >5 mmol/l. Either 1 or 2 points were
attributed to each variable, leading to a score in 3 risk categories: low (0 to
2), intermediate (3 or 4), and high (5 to 9). The observed 30-day mortality rates
were 23.8%, 49.2%, and 76.6%, respectively (p < 0.0001). Validation in the IABP
SHOCK II registry population showed good discrimination with an area under the
curve of 0.79. External validation in the CardShock trial population (n = 137)
showed short-term mortality rates of 28.0% (score 0 to 2), 42.9% (score 3 to 4),
and 77.3% (score 5 to 9; p < 0.001) and an area under the curve of 0.73. Kaplan
Meier analysis revealed a stepwise increase in mortality between the different
score categories (0 to 2 vs. 3 to 4: p = 0.04; 0 to 2 vs. 5 to 9: p = 0.008).
CONCLUSIONS: The IABP-SHOCK II risk score can be easily calculated in daily
clinical practice and strongly correlated with mortality in patients with infarct
related CS. It may help stratify patient risk for short-term mortality and might,
thus, facilitate clinical decision making. (Intraaortic Balloon Pump in
Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036).
PMID- 28408021
TI - Risk Prediction in AMI Shock: Goldilocks and the Search for "Just Right".
PMID- 28408023
TI - On the Road to Full Cardiac Recovery With Mechanical Unloading: Are We There Yet?
PMID- 28408022
TI - Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced
Heart Failure.
AB - BACKGROUND: Left ventricular assist devices (LVADs) have been used as an
effective therapeutic option in patients with advanced heart failure, either as a
bridge to transplantation, as destination therapy, or in some patients, as a
bridge to recovery. OBJECTIVES: This study evaluated whether patients undergoing
an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional
capacities equivalent to those of healthy controls. METHODS: Fifty-eight male
patients-18 implanted with a continuous-flow LVAD, 16 patients with LVAD
explanted (recovered patients), and 24 heart transplant candidates (HTx)-and 97
healthy controls performed a maximal graded cardiopulmonary exercise test with
continuous measurements of respiratory gas exchange and noninvasive (rebreathing)
hemodynamic data. Cardiac function was represented by peak exercise cardiac power
output (mean arterial blood pressure * cardiac output) and functional capacity by
peak exercise O2 consumption. RESULTS: All patients demonstrated a significant
exertional effort as demonstrated with the mean peak exercise respiratory
exchange ratio >1.10. Peak exercise cardiac power output was significantly higher
in healthy controls and explanted LVAD patients compared with other patients
(healthy 5.35 +/- 0.95 W; explanted 3.45 +/- 0.72 W; LVAD implanted 2.37 +/- 0.68
W; and HTx 1.31 +/- 0.31 W; p < 0.05), as was peak O2 consumption (healthy 36.4
+/- 10.3 ml/kg/min; explanted 29.8 +/- 5.9 ml/kg/min; implanted 20.5 +/- 4.3
ml/kg/min; and HTx 12.0 +/- 2.2 ml/kg/min; p < 0.05). In the LVAD explanted
group, 38% of the patients achieved peak cardiac power output and 69% achieved
peak O2 consumption within the ranges of healthy controls. CONCLUSIONS: The
authors have shown that a substantial number of patients who recovered
sufficiently to allow explantation of their LVAD can even achieve cardiac and
physical functional capacities nearly equivalent to those of healthy controls.
PMID- 28408025
TI - Echocardiographic Algorithms for Detecting Elevated Diastolic Pressures:
Reasonable, Not Perfect.
PMID- 28408024
TI - Estimating Left Ventricular Filling Pressure by Echocardiography.
AB - BACKGROUND: The diagnosis of heart failure may be challenging because symptoms
are rather nonspecific. Elevated left ventricular (LV) filling pressure may be
used to confirm the diagnosis, but cardiac catheterization is often not
practical. Echocardiographic indexes are therefore used as markers of filling
pressure. OBJECTIVES: This study investigated the feasibility and accuracy of
comprehensive echocardiography in identifying patients with elevated LV filling
pressure. METHODS: We conducted a multicenter study of 450 patients with a wide
spectrum of cardiac diseases referred for cardiac catheterization. Left atrial
volume index, in combination with flow velocities and tissue Doppler velocities,
was used to estimate LV filling pressure. Invasively measured pressure was used
as the gold standard. RESULTS: Mean left ventricular ejection fraction (LVEF) was
47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated
LV filling pressure in 58% of patients. Clinical assessment had an accuracy of
72% in identifying patients with elevated filling pressure, whereas
echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The
combination of clinical and echocardiographic assessment was incremental, with a
net reclassification improvement of 1.5 versus clinical assessment (p < 0.001).
CONCLUSIONS: Echocardiographic assessment of LV filling pressure is feasible and
accurate. When combined with clinical data, it leads to a more accurate
diagnosis, regardless of LVEF.
PMID- 28408026
TI - The Aging Cardiovascular System: Understanding It at the Cellular and Clinical
Levels.
AB - Cardiovascular disease (CVD) presents a great burden for elderly patients, their
caregivers, and health systems. Structural and functional alterations of vessels
accumulate throughout life, culminating in increased risk of developing CVD. The
growing elderly population worldwide highlights the need to understand how aging
promotes CVD in order to develop new strategies to confront this challenge. This
review provides examples of some major unresolved clinical problems encountered
in daily cardiovascular practice as we care for elderly patients. Next, the
authors summarize the current understanding of the mechanisms implicated in
cardiovascular aging, and the potential for targeting novel pathways implicated
in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling,
and genomic instability. Lastly, the authors consider critical aspects of
vascular repair, including autologous transplantation of bone marrow-derived stem
cells in elderly patients.
PMID- 28408027
TI - Is Atrial Fibrillation a Preventable Disease?
AB - Atrial fibrillation (AF) is an increasing burden worldwide. However, AF
prevention has not been emphasized enough in clinical practice or guidelines. In
this paper, the authors review the associations of modifiable lifestyle factors,
including alcohol abuse, smoking, physical inactivity, and unhealthy
psychological stress, with the risk for AF development. The authors also review
the associations of cardiovascular risk factors that can be better managed,
including obesity and overweight, high blood pressure, diabetes, dyslipidemia,
obstructive sleep apnea, and other cardiovascular diseases, with the risk for AF.
The conclusion is that a high proportion of AF can be prevented by combining
strategies, focusing on the high-risk population for better risk factor
management, and emphasizing healthy lifestyle choices in the whole population.
PMID- 28408028
TI - Manuscripts Based on Datasets Shared by Clinical Research Studies.
PMID- 28408029
TI - Advanced Heart Failure in the ACHD Population: Finding the Fellows' Role in a
Growing Field.
PMID- 28408030
TI - Prethrombotic State in Young Very Low-Risk Patients With Atrial Fibrillation.
PMID- 28408032
TI - Baseline or Post-Procedural High-Sensitivity Troponin?: Probably Both.
PMID- 28408031
TI - Prediction of Systemic Septic Embolism in Patients With Left-Sided Infective
Endocarditis.
PMID- 28408033
TI - Reply: Baseline or Post-Procedural High-Sensitivity Troponin? Probably Both.
PMID- 28408034
TI - Cost Effectiveness of Nonstatin-to-Statin Therapy.
PMID- 28408035
TI - Reply: Cost Effectiveness of Nonstatin-to-Statin Therapy.
PMID- 28408036
TI - Correction.
PMID- 28408037
TI - Reduced Anxiety and Depression in Patients With Advanced Heart Failure After Left
Ventricular Assist Device Implantation.
AB - BACKGROUND: Despite the high prevalence of depression and anxiety in patients
with advanced heart failure, the effects of left ventricular assist device (LVAD)
implantation on these critically important aspects of mental health are not well
understood. OBJECTIVE: We sought to assess changes in depression and anxiety
following LVAD implantation. METHODS: The Beck Depression Inventory-II (BDI-II)
and Beck Anxiety Inventory (BAI) were administered to 54 patients by a clinical
psychologist at a mean of 12 days before LVAD implantation and 251 days after
implantation. Patient demographics and clinical data were collected concurrently
to psychologic testing. Changes in BDI-II, BAI, and clinical markers of heart
failure were assessed using paired t-tests. A p < 0.05 was considered
significant. RESULTS: The average age of the group was 56.63 years with a mean
ejection fraction 20.8%. Before implantation, mean BAI and BDI scores indicated
mild depression and anxiety. Following LVAD implantation, average scores for both
BDI-II and BAI decreased significantly, indicating minimal depression and anxiety
(12.6-8.54, p = 0.001 and 12.06-6.6, p < 0.001, respectively). Mean scores were
significantly lowered in 11 and 8 of the 21 subdomains tested by the BAI and BDI,
respectively. Significant improvements were noted in post-LVAD B-type natriuretic
peptide, serum sodium, and blood urea nitrogen. CONCLUSION: Depression and
anxiety scores improved significantly after LVAD implantation. Factors
contributing to changes in depression and anxiety after LVAD could be related to
the improvement in acute heart failure symptoms, functional capacity, and quality
of life. Prospective studies with larger sample sizes are warranted.
PMID- 28408038
TI - Temporal Relation between Macular Ganglion Cell-Inner Plexiform Layer Loss and
Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma.
AB - PURPOSE: To investigate the temporal relationship between inferior macular
ganglion cell-inner plexiform layer (mGCIPL) loss and corresponding peripapillary
retinal nerve fiber layer (pRNFL) defect on the optical coherence tomography
(OCT) deviation map in glaucoma. DESIGN: Retrospective, observational study.
PARTICIPANTS: A total of 151 patients with early-stage glaucoma (visual field
[VF] mean deviation between -1.5 and -5.5 decibels [dB]). METHODS: Spectral
domain OCT mGCIPL and pRNFL deviation maps were obtained for the baseline (from
January 2012 to August 2012) and again for the follow-up (from January 2015 to
August 2015). An integrated deviation map thereafter was merged by vascular
landmark-guided superimposition of mGCIPL and pRNFL deviation maps onto RNFL
imagery. On the basis of an earlier schematic model, the inferotemporal
peripapillary area was divided into (1) the macular vulnerability zone (MVZ) and
(2) the inferoinferior portion. MAIN OUTCOME MEASURES: Temporal sequence of
inferior mGCIPL loss and corresponding pRNFL (i.e., pRNFL in MVZ) defect on
integrated deviation map. RESULTS: At baseline, 99 (65.6%) of the 151 eyes showed
inferior mGCIPL loss. In addition, 112 eyes (74.2%) and 5 eyes (3.3%) showed
inferoinferior pRNFL defect and pRNFL defect in the MVZ, respectively. At the 3
year follow-up, 112 (74.2%) of the eyes showed inferior mGCIPL loss, whereas 123
eyes (81.5%) and 25 eyes (16.6%) showed inferoinferior pRNFL defect and pRNFL
defect in the MVZ, respectively. Ninety-four eyes initially showed inferior
mGCIPL loss without pRNFL defect in the MVZ; among them, 19 (20.2%) subsequently
showed defect during the 3-year follow-up interval. Meanwhile, among the 52 eyes
without preexisting inferior mGCIPL loss, only 1 (1.9%; P < 0.001) developed a
pRNFL defect in the MVZ during the 3-year follow-up interval. CONCLUSIONS: In
eyes with early glaucoma, mGCIPL change is frequently detected before
corresponding pRNFL change. This could be the result of a superior sensitivity of
mGCIPL deviation map that allows detection of an abnormality in the mGCIPL
thickness earlier. In this light, OCT pRNFL analysis alone likely would overlook
macular damage. Macular OCT imaging should be included in the imaging algorithm
for the serial observation of patients with glaucoma.
PMID- 28408039
TI - Binocular Measures of Visual Acuity and Visual Field versus Binocular
Approximations.
AB - PURPOSE: To assess the relationship of binocular visual function tests with
binocular approximations using data from the Collaborative Initial Glaucoma
Treatment Study (CIGTS). DESIGN: Case series based on existing data from a
clinical trial. PARTICIPANTS: Six hundred seven patients with newly diagnosed
open-angle glaucoma from the CIGTS. METHODS: Monocular visual field (VF) and
visual acuity (VA) tests were performed at baseline and every 6 months
thereafter. Binocular tests of visual function (Esterman VF score, binocular VA)
were added to the CIGTS protocol 3 years into the study. The binocular
approximations of binocular visual function were better or worse eye, average
eye, better or worse location, and binocular summation or pointwise binocular
summation. Associations between binocular tests and binocular approximations to
represent binocular visual function were assessed with Pearson's correlations
(r), as was the relationship between vision-related quality of life (VR QOL;
Visual Activities Questionnaire [VAQ] and the 25-item National Eye Institute
Visual Function Questionnaire [NEI VFQ-25]) and binocular tests or binocular
approximations of visual function. MAIN OUTCOME MEASURES: Binocular visual
function (VF and VA) and VR QOL. RESULTS: Five hundred seventy-five patients
underwent at least 1 binocular visual function test. The Esterman score was
correlated significantly with all binocular approximations of VF, with r values
ranging from 0.31 (worse-eye mean deviation [MD]) to 0.42 (better-eye MD; P <
0.0001 for all). Binocular VA showed stronger correlations with binocular
approximations, with r values ranging from 0.65 (worse-eye VA) to 0.80 (binocular
summation; P < 0.0001 for all). Correlations between the VAQ and Esterman score
were stronger in 7 of 9 subscales (r = -0.14 to -0.25; P < 0.05 for all) than
correlations with all 7 binocular approximations. In contrast, correlations
between the VAQ and binocular VA (r = -0.07 to -0.21) were weaker in all
subscales than those with better-eye, average-eye, and binocular summation of VA
(r = -0.12 to -0.25), but not different from worse-eye values. These trends also
were found in relevant subscales of the NEI VFQ-25. CONCLUSIONS: We found limited
benefit in binocular testing of VA in the clinical setting as a means of
approximating a patient's reported visual functioning. In contrast, we found some
benefit in performing binocular VF testing, because the results correlated more
closely with reported functioning than binocular approximations.
PMID- 28408040
TI - Myxomatous Degeneration of the Canine Mitral Valve: From Gross Changes to
Molecular Events.
AB - Myxomatous mitral valve disease (MMVD) is the single most common acquired heart
disease of the dog, but is also of emerging importance in human medicine, with
some features of the disease shared between both species. There has been
increased understanding of this disease in recent years, with most research
aiming to elucidate the cellular and molecular events of disease pathogenesis.
For gross and histological changes, much of our understanding is based on
historical studies and there has been no comprehensive reappraisal of the
pathology of MMVD. This paper reviews the gross, histological, ultrastructural,
cellular and molecular changes in canine MMVD.
PMID- 28408041
TI - Nontraumatic head and neck injuries: a clinical approach. Part 2.
AB - Nontraumatic emergencies of the head and neck represent a challenge in the field
of neuroradiology for two reasons. As explained in the first part of this update,
these entities affect an area where the thorax joins the cranial cavity and can
thus compromise both structures; second, they are uncommon, so they are not well
known. Maintaining the same approach as in the first part, focusing on the
clinical presentations in the emergency department rather than on the anatomic
regions affected, we will study the entities that present with two patterns:
those that present with a combination of cervical numbness, dysphagia, and
dyspnea and those that present with acute sensory deficits. In the latter group,
we will specifically focus on visual deficits, because this is the most common
symptom that calls for urgent imaging studies.
PMID- 28408042
TI - Towards the determination of sulfonamides in meat samples: A magnetic and
mesoporous metal-organic framework as an efficient sorbent for magnetic solid
phase extraction combined with high-performance liquid chromatography.
AB - A magnetic, mesoporous core/shell structured Fe3O4@JUC-48 nanocomposite was
synthesized and employed as a magnetic solid phase extraction (MSPE) sorbent for
the determination of trace sulfonamides (SAs) in meat samples. The synthesized
nanocomposite was characterized by X-ray diffraction, Fourier transform infrared
spectra, transmission electron microscopy, scanning electron microscopy, Brunner
Emmet-Teller, and vibrating sample magnetometry; the Fe3O4@JUC-48 nanocomposite
exhibited a distinctive morphology, large surface area, high magnetism, open
adsorption sites, and high chemical stability. By combining the optimized MSPE
conditions with high performance liquid chromatography diode array detection, an
accurate and sensitive method for the determination of 5 SAs, including
sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine
(SMZ), and sulfamethoxypyridazine (SMP), was developed. The method exhibited good
linearity in the range of 3.97-1000ng/g with R ranging from 0.9991 to 0.9994,
high sensitivity with LODs ranging from 1.73 to 5.23ng/g, adequate recoveries
between 76.1 and 102.6% with low relative standard deviations ranging from 2.1 to
6.4%, and high precision with RSD<4.5%. The Fe3O4@JUC-48 magnetic nanocomposite
is a promising sorbent for the rapid and efficient extraction of SAs from complex
biological samples such as chicken, pork, and shrimp.
PMID- 28408043
TI - A review on solid phase extraction of actinides and lanthanides with amide based
extractants.
AB - Solid phase extraction is gaining attention from separation scientists due to its
high chromatographic utility. Though both grafted and impregnated forms of solid
phase extraction resins are popular, the later is easy to make by impregnating a
given organic extractant on to an inert solid support. Solid phase extraction on
an impregnated support, also known as extraction chromatography, combines the
advantages of liquid-liquid extraction and the ion exchange chromatography
methods. On the flip side, the impregnated extraction chromatographic resins are
less stable against leaching out of the organic extractant from the pores of the
support material. Grafted resins, on the other hand, have a higher stability,
which allows their prolong use. The goal of this article is a brief literature
review on reported actinide and lanthanide separation methods based on solid
phase extractants of both the types, i.e., (i) ligand impregnation on the solid
support or (ii) ligand functionalized polymers (chemically bonded resins). Though
the literature survey reveals an enormous volume of studies on the extraction
chromatographic separation of actinides and lanthanides using several
extractants, the focus of the present article is limited to the work carried out
with amide based ligands, viz. monoamides, diamides and diglycolamides. The
emphasis will be on reported applied experimental results rather than on data
pertaining fundamental metal complexation.
PMID- 28408044
TI - Determination of 82 veterinary drugs in swine waste lagoon sludge by ultra-high
performance liquid chromatography-tandem mass spectrometry.
AB - This work reports the development of a multi-residue method for the
identification and quantification of 82 veterinary drugs belonging to different
chemical classes in swine waste lagoon. The proposed method applies a solid-phase
extraction procedure with Oasis PRiME HLB cartridges that combines isolation of
the compounds and sample clean-up in a single step. Analysis is performed by
ultra-high performance liquid chromatography-tandem mass spectrometry, in one
single injection with a chromatographic run time of only 9.5min. Linearity was
studied in the range between 1 and 500MUgkg-1 using standards prepared both in
pure solvent and in the presence of matrix, showing coefficients of determination
higher than 0.99 for all the analytes except for cefapirin in matrix. The average
recoveries were in the range of 60-110% for most of the compounds tested with
inter-day relative standard deviations below 17%. More than 97% of the
investigated compounds had less or equal to a 5MUgkg-1 quantitation limit in the
studied matrix. Finally, the method was used with success to detect and quantify
veterinary drugs residues in real samples with sulfonamides, quinolones, and
tetracyclines being the most frequently determined compound groups.
PMID- 28408045
TI - Erratum to "Starch-enhanced degradation of HMW PAHs by Fusarium sp. in an aged
polluted soil from a coal mining area" [Chemosphere 174C (2017), 774-780].
PMID- 28408046
TI - [Evaluation of practices in the management of scabies in children].
AB - BACKGROUND: Scabies has been on the rise in France in recent years and has posed
therapeutic problems, mainly due to the withdrawal of benzyl benzoate. The
objective of this study was to describe prescribing practices for scabies in
children. METHODS: A national survey was conducted by means of a standardized
questionnaire covering various clinical situations of scabies and the drugs used
preferentially according to age, which was sent out between December 2014 and
March 2015 to members of the clinical research group of the French Society of
Paediatric Dermatology. RESULTS: Of the 38 experts contacted, 20 replied. For a
typical case of scabies, 55% of the experts initially prescribed oral ivermectin
for children aged 6 years, 15% prescribed ivermectin in children aged 2 years,
and 5% in infants aged 3 months. Ivermectin was more widely prescribed after
failure of prior treatment or recurrence of scabies, on skin lesions or impetigo,
if precarious, especially for profuse hyperkeratotic scabies. A total of 35% of
the experts reported no prescribing restrictions with regard to patient age or
weight. Discrepancies were observed concerning the mode of administration and the
time between consecutive doses. Esdepallethrin remained the preferred local
treatment among the experts (38% of all topical prescriptions) except in
asthmatic children, while permethrin was the least-prescribed topical agent.
DISCUSSION: This study confirms the heterogeneity of our practices. Formal expert
recommendations are awaited, particularly concerning the use of ivermectin in
infants.
PMID- 28408047
TI - Psychology and psychiatry in Singapore courts: A baseline survey of the mental
health landscape in the legal arena.
AB - Despite the increasing prevalence and involvement of mental health professionals
in local courts, there has been no systematic study of the role played by these
expert witnesses in Singapore courtrooms. An empirical study of all existing
recorded cases on Lawnet (Singapore's legal database of all court trial cases)
from 1975-2014 involving psychologists and psychiatrists was conducted. Results
revealed that, not only were these mental health experts increasingly dotting the
landscape of the legal arena, the variety of their contributions has also been
gradually growing. Furthermore, there were marked differences across criminal,
civil and custody cases with regards to the issues of how these experts were
consulted and how their inputs utilized and appreciated by judges. Differences
between psychology and psychiatry were also apparent. A future with more
assistance rendered by these professions to courts, as well as greater synergy
between law and mental health, was predicted for Singapore courts.
PMID- 28408048
TI - Distribution pattern of anthropogenic marine debris along the gastrointestinal
tract of green turtles (Chelonia mydas) as implications for rehabilitation.
AB - Pollution from anthropogenic marine debris (AMD) is currently the most widely
distributed and lasting anthropic impact in the marine environment, affecting
hundreds of species, including all sea turtles. In this study, the patterns of
AMD distribution along the gastrointestinal tract (GT) and their relationship
with obstructions and faecalomas in 62 green turtles (Chelonia mydas) that died
during rehabilitation in southern Brazil were determined. The GT was split in
seven sections, corresponding to the natural organs and intestinal areas
morphologically and physiologically distinct. Mean mass (4.24g) and area
(146.74cm2) of AMD in the stomach were higher than in other sections. The
anterior portion of the rectum had the highest number of obstructions, followed
by the stomach. AMD was associated with the obstructions, with positive
correlation between faecalomas and AMD masses. Organs and subdivisions showed
marked differences in susceptibility to obstructions caused by AMD, which
deserves attention in clinical interventions.
PMID- 28408049
TI - Ultrasound-responsive NIPAM-based hydrogels with tunable profile of controlled
release of large molecules.
AB - Episodic release of bioactive compounds plays an important role in biological
systems. "On-demand" release systems which based on polymeric materials and
activated by external stimuli may provide the necessary functionality. Here we
describe an ultrasound-responsive hydrogel based on N-isopropylacrylamide (NIPAM)
and N,N'-methylenebisacrylamide (MBAm), which is suitable for triggered release
of two large molecules: bovine serum albumin (BSA, 66kDa) and dextran (3-5kDa).
It is shown that the release amount of these two large molecules increased with
increasing hydrogel temperature, and the application of ultrasound further
increased the release. By simply adjusting the contents of NIPAM and MBAm, the
difference of BSA release between the presence and absence of ultrasound could be
adjusted from 2.7 to 84 folds. There was also a positive correlation between the
ultrasound intensity and release amount. These properties made the NIPAM-based
hydrogel a tunable platform for focal drug delivery.
PMID- 28408050
TI - Leiomyomatosis peritonealis disseminata.
PMID- 28408051
TI - Beyond Body Mass Index. Is the Body Cell Mass Index (BCMI) a useful prognostic
factor to describe nutritional, inflammation and muscle mass status in
hospitalized elderly?: Body Cell Mass Index links in elderly.
AB - BACKGROUND & AIM: The aim of this study was to establish the effectiveness of
Body Cell Mass Index (BCMI) as a prognostic index of (mal)nutrition, inflammation
and muscle mass status in the elderly. METHODS: A cross-sectional observational
study has been conducted on 114 elderly patients (80 women and 34 men), with mean
age equal to 81.07 +/- 6.18 years. We performed a multivariate regression model
by Structural Equation Modelling (SEM) framework. We detected the effects over a
Mini Nutritional Assessment (MNA) stratification, by performing a multi-group
multivariate regression model (via SEM) in two MNA nutritional strata, less and
bigger (or equal) than 17. RESULTS: BCMI had a significant effect on albumin
(beta = +0.062, P = 0.001), adjusting for the other predictors of the model as
Body Mass Index (BMI), age, sex, fat mass and cognitive condition. An analogous
result is maintained in MNA<17 stratum. BMI has confirmed to be a solid
prognostic factor for both free fat mass (FFM) (beta = +0.480, P < 0.001) and
Skeletal Muscle Index (SMI) (beta = +0.265, P < 0.001), assessed by DXA. BCMI
also returned suggestive evidences (0.05 < P < 0.10) for both the effect on FFM
and on SMI in overall sample. CONCLUSIONS: The main result of this study is that
the BCMI, compared to BMI, proved to be significantly related to an important
marker as albumin in geriatric population. Then, assessing the BCMI could be a
valuable, inexpensive, easy to perform tool to investigate the inflammation
status of elderly patients.
PMID- 28408052
TI - Reply to: Caution using the new "no pain no gain" approach.
PMID- 28408053
TI - Improvement in the management of patients with Clostridium difficile associated
diarrhoea following changes to the wording of laboratory reports.
PMID- 28408054
TI - Radiation therapy quality indicators for invasive breast cancer.
AB - BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer has evolved
considerably over the past two decades. A concise list of optimal care indexes is
lacking. The purpose of this project was to generate a suite of quality of care
indicators for breast cancer RT. MATERIALS AND METHODS: A modified Delphi
approach was used including a comprehensive literature and guideline review (1995
2015), an initial review of potential quality indicators (QIs) by a steering
committee, a survey of Canadian Radiation Oncologists, and a face-to-face
consensus development meeting with breast cancer experts to develop a list of
breast RT quality indicators. RESULTS: The literature review identified 163
potential QIs, which was reduced to 73 by the steering committee. After all
rounds of the Delphi process the final suite included 33 QIs. Of these, 28 (85%)
received at least 80% acceptance from the Radiation Oncologists who participated
in the final online survey. CONCLUSIONS: A suite of measureable RT quality
indicators to be considered during management of invasive breast cancer was
developed. These indicators could be used to assess the quality and consistency
of breast cancer RT practices.
PMID- 28408055
TI - A lesson in controlling for third factors and reading before you write: A reply
to Giannouli.
PMID- 28408057
TI - Congenital Bi-segmental Bronchial Atresia with Areas of Congenital Pulmonary
Airway Malformation.
PMID- 28408056
TI - Repair of Iatrogenic Tracheobronchial Injury With Synthetic Dural Graft.
PMID- 28408058
TI - Security "high-tech" individual extra-light device mask 2.0: CAD/CAM evolution.
AB - In 2008, we presented our security "high-tech" individual extra-light device mask
(SHIELD), a protective shield based on the face cast of an injured soccer player
that can be customised. It allows a shortened convalescent period, is
comfortable, fits well, and allows the patient to continue to play at a
professional level in their chosen sport or activity in the shortest time
possible. It has been used often in both amateur and professional categories of
many sports, and we now present an update.
PMID- 28408059
TI - Effect of a high-protein, high-fiber diet plus supplementation with branched
chain amino acids on the nutritional status of patients with cirrhosis.
AB - INTRODUCTION AND OBJECTIVES: The potential benefits of branched-chain amino acids
(BCAAs) in cirrhosis extend beyond just the improvement of nutritional status.
Their effects include improvement of glucose tolerance, oxidative stress, and
inflammatory markers, as has been shown in several studies. A dual nutritional
approach of a high-protein, high-fiber diet plus BCAAs in cirrhosis could have
additional benefits, compared with BCAAs alone. Such an approach has not been
explored and therefore the aim of the present study was to evaluate the effect of
a combination of a high-protein, high-fiber diet plus BCAA supplementation over a
6-month period of time on the nutritional status of patients with cirrhosis, as
well as its safety and tolerability for those same patients. METHODS: An open,
randomized clinical trial was conducted. Patients were randomized to one of two
groups: the BCAAs+HPHF diet intervention group: a high-protein, high-fiber diet
with 1.2g/kg protein and 30g of fiber plus supplementation with oral branched
chain amino acids 110g daily and the HPHF diet control group: a high-protein,
high-fiber diet with 1.2g/kg protein and 30g of fiber. The differences between
the treatment groups were compared using the unpaired T test and the differences
at the end of treatment were compared using the paired T test. RESULTS: A total
of 72 patients were included, 37 in the intervention group and 35 in the control
group. At the end of the study period, ammonia and glucose levels showed no
significant increase in either group, reflecting the safety of the BCAA
supplement. Furthermore, muscle and fat mass were evaluated through triceps
skinfold thickness and mid-arm muscle circumference measurements. There was an
increase in muscle mass and a decrease in fat mass in the BCAA group, but not in
the control group. After the intervention, there were no significant changes in
the Psychometric Hepatic Encephalopathy Score or the Critical Flicker Frequency
score results in either group, and no episodes of hepatic encephalopathy were
observed during the treatment period. CONCLUSION: Supplementation with branched
chain amino acids plus a high-fiber, high-protein diet is a safe intervention in
patients with cirrhosis. It helps increase muscle mass and does not raise the
levels of ammonia or glucose, nor is it associated with the development of
hepatic encephalopathy.
PMID- 28408060
TI - Bacterial epidemiology and antimicrobial resistance profiles of urinary specimens
of the elderly.
AB - OBJECTIVE: Although urinary tract infections are the second leading cause of
infections among patients aged above 65 years, data on bacterial epidemiology of
urinary specimens in these patients is scarce. Our aim was to describe the main
bacterial species found at significant levels in urine specimens of the elderly
and to determine their antimicrobial resistance profiles. METHODS: From October
2012 to October 2015, all urinary specimens (catheter-related or not) received at
the laboratory of microbiology of the university hospital of Caen (France) were
retrospectively studied. Results were compared to those of urinary specimens of
patients aged 18-64 years. Bacterial identification was performed using MALDI-TOF
mass spectrometry and antimicrobial susceptibility testing was performed as per
CA-SFM guidelines. RESULTS: Out of 33,302 urine cytobacteriological examinations
(UCBE) performed in patients aged above 65 years, 13,450 microorganisms were
identified. Escherichia coli was the most frequent species (41.8%) followed by
Enterococcus faecalis (9.7%), Pseudomonas aeruginosa (5.7%), Proteus mirabilis
(4.6%), and Klebsiella pneumoniae (4.2%). Around 9% of E. coli isolates were
resistant to third-generation cephalosporins, including 8.2% by production of
extended-spectrum beta-lactamase (ESBL). This prevalence was significantly higher
than that observed in urinary specimens of patients aged 18-74 years (4.9%,
P<0.001). CONCLUSION: The bacterial epidemiology of urines collected from the
elderly is diverse and significantly different from that of urine specimens of
younger patients, with a higher proportion of multidrug-resistant bacteria
(particularly ESBL-producing E. coli).
PMID- 28408061
TI - Predicting Tissue Susceptibility to Mechanical Cavitation Damage in Therapeutic
Ultrasound.
AB - Histotripsy is a developing focused ultrasound procedure that uses cavitation
bubbles to mechanically homogenize soft tissue. To better understand the
mechanics of tissue damage, a numerical model of single-bubble dynamics was used
to calculate stress, strain and strain rate fields produced by a cavitation
bubble exposed to a tensile histotripsy pulse. The explosive bubble growth and
its subsequent collapse were found to depend on the properties of the surrounding
material and on the histotripsy pulse. Stresses far greater than gigapascals were
observed close to the bubble wall, but attenuated by four to six orders of
magnitude within 50 MUm from the bubble wall, with at least two orders of
magnitude attenuation occurring within the first 10 MUm from the bubble. Elastic
stresses were found to dominate close to the bubble wall, whereas viscous
stresses tended to persist farther into the surroundings. A non-dimensional
parameter combining tissue, waveform and bubble properties was identified that
dictates the dominant stress (viscous vs. elastic) as a function of distance from
the bubble nucleus. In a cycle of bubble growth and collapse, characteristic
times at which mechanical damage is likely to occur and dominant mechanisms
acting at each time were identified.
PMID- 28408062
TI - Novel Method for Vessel Cross-Sectional Shear Wave Imaging.
AB - Many studies have investigated the applications of shear wave imaging (SWI) to
vascular elastography, mainly on the longitudinal section of vessels. It is
important to investigate SWI in the arterial cross section when evaluating
anisotropy of the vessel wall or complete plaque composition. Here, we proposed a
novel method based on the coordinate transformation and directional filter in the
polar coordinate system to achieve vessel cross-sectional shear wave imaging. In
particular, ultrasound radiofrequency data were transformed from the Cartesian to
the polar coordinate system; the radial displacements were then estimated
directly. Directional filtering was performed along the circumferential direction
to filter out the reflected waves. The feasibility of the proposed vessel cross
sectional shear wave imaging method was investigated through phantom experiments
and ex vivo and in vivo studies. Our results indicated that the dispersion
relation of the shear wave (i.e., the guided circumferential wave) within the
vessel can be measured via the present method, and the elastic modulus of the
vessel can be determined.
PMID- 28408063
TI - [Cutaneous lesions and polyarthritis].
PMID- 28408064
TI - [Transcatheter aortic valve implantation: What remains of aortic stenosis
surgery?]
PMID- 28408065
TI - Cheaper, Faster, or Better: Are simple estimations of safety parameters of
hazardous materials reliable? Comments on "Thermal behaviors, nonisothermal
decomposition reaction kinetics, thermal safety and burning rates of BTATz-CMDB
propellant" by Zhao et al. (2010).
PMID- 28408066
TI - Derivation and Validation of a Scoring System for Intravenous Tissue Plasminogen
Activator Use in Asian Patients.
AB - BACKGROUND AND PURPOSE: As Chinese Asian populations have an increased risk of
intracerebral hemorrhage (ICH) after intravenous tissue plasminogen activator (IV
tPA), we aimed to design a rapid, clinically applicable risk scoring system to
predict ICH and functional outcomes after IV tPA treatment in Asian ischemic
stroke patients. METHODS: From January 2009 to December 2012, consecutive acute
ischemic stroke patients treated with IV tPA recruited from the Stroke Registry
in Chang Gung Healthcare System (SRICHS) in Taiwan and the National University
Hospital of Singapore (NUHS) acute stroke database were used to create and
validate a scoring system. Nomogram was created for ICH and 3-month mortality.
RESULTS: In total, 932 patients were included in the study: 386 from SRICHS for
the derivation of scoring system and 546 from NUHS to validate it. We used
nomograms to assign weightage to the scoring system. The presence of atrial
fibrillation, glucose level, and the National Institutes of Health Stroke Scale
(NIHSS) score were significantly associated with the risk of ICH. Age, NIHSS
score, hyperlipidemia, and the presence of post-tPA ICH were significantly
associated with mortality. The areas under the curve of derivation and validation
cohorts were .663 and .662 for ICH, and .808 and .790 for mortality,
respectively. CONCLUSIONS: The scoring system using nomograms can provide a fast,
practical, and user-friendly tool that allows physicians to predict the risk of
ICH and functional outcomes with IV tPA treatment in a clinical setting.
PMID- 28408067
TI - Polyphenol supplementation inhibits physiological increase of prostaglandin E2
during reproductive period - A randomized clinical trial.
AB - Anti-inflammatory property of polyphenols and their effect on the metabolism of
prostaglandins is not established in healthy humans. This study aimed to evaluate
the effect of polyphenol supplementation in plasma levels of prostaglandin E2 and
other markers of inflammation and oxidative stress in women using contraceptives.
In this randomized double-blind clinical trial, women aged 25-35 years were
selected. Participants received capsules containing polyphenols or placebo, to be
consumed for fifteen days. From 40 women randomized, 28 completed the study.
Control group showed a significant increase in the levels of PGE2 (p=0.01) while
the polyphenols group showed no change in these levels (p=0.79). There was an
increase in hs-CRP (p<0.01) and F2-isoprostane (p=0.04) in the control group. The
GSSG to GSH ratio significantly reduced in the polyphenols group (p=0.02).
Supplementation with polyphenol capsules inhibited the increase in markers of
inflammation and oxidative stress in women of childbearing age using combined
hormonal contraceptives.
PMID- 28408068
TI - Quercus infectoria inhibits Set7/NF-kappaB inflammatory pathway in macrophages
exposed to a diabetic environment.
AB - Chronic inflammation plays a key role in the pathogenesis of myriad complications
associated with diabetes and thus anti-inflammatory therapies may ameliorate
these complications. Quercus infectoria (Qi) extract has been shown to
downregulate inflammatory processes; however, the molecular mechanisms of this
anti-inflammatory activity remain unclear. The hypothesis of our study was that
Qi extract exerts its anti-inflammatory effect by downregulating the Set7/NF
kappaB pathway. Bone marrow-derived macrophages (BMM) were treated with high
glucose plus palmitate medium (HG/Pa) to simulate the diabetic environment.
Compared with control conditions, HG/Pa elevated expression Set7, expression and
activity of NF-kappaB along with expression of several inflammatory cytokines.
These changes were associated with increased levels of intracellular reactive
oxygen species (ROS). Moreover, similar alterations were demonstrated in BMM
derived from mice fed a high fat diet (HFD) compared to those from lean mice,
suggesting that HFD-induced changes in BM progenitors persist throughout
differentiation and culture. Importantly, Qi extract dose-dependently reduced
Set7, p65 and inflammatory cytokine expression relative to vehicle controls in
both HG/Pa-and HFD-treated BMM. Finally, macrophages/monocytes isolated from
wounds of diabetic mice that were treated with Qi solution exhibited lower
expression of the inflammatory cytokines, IL-1beta and TNF-alpha, compared with
vehicle treated wounds, demonstrating translation to the in vivo diabetic
environment. Taken together, data from this study suggests that Qi downregulates
diabetes-induced activity of the Set7/NF-kB pathway.
PMID- 28408069
TI - TLR7-mediated activation of XBP1 correlates with the IFNalpha production in
humans.
AB - The transcription factor X-box binding protein 1 (XBP1) represents a key
component of the endoplasmatic reticulum (ER) stress response and is required for
the production of several pro-inflammatory cytokines. XBP1 is furthermore
essential for the development and survival of plasmacytoid dendritic cells
(pDCs), and has recently been suggested to be involved in toll-like receptor
(TLR) 2/4 signaling. Activation of TLR7 on pDCs results in an upregulation of pro
inflammatory cytokines, such as type I interferons (IFN-I), and has been
implicated in several autoimmune and inflammatory diseases, but the role of XBP1
in this process remains unknown. Here, we show that signaling via TLR7 leads to
an upregulation of XBP1 and IFNalpha-production. XBP1 mRNA expression levels
positively correlated with the production of IFNalpha, while blocking of XBP1
mRNA splicing significantly reduced mRNA transcripts of IFNalpha. In conclusion,
these data suggest a central role of XBP1 in TLR7-induced IFNalpha production and
identify XBP1 as a potential novel therapeutic target in IFNalpha-driven
autoimmune and inflammatory diseases.
PMID- 28408071
TI - Error, contradiction and reversal in science and medicine.
AB - Error and contradictions are not "per se" detrimental in science and medicine.
Going back to the history of philosophy, Sir Francis Bacon stated that "truth
emerges more readily from error than from confusion", and recently Popper
introduced the concept of an approximate temporary truth that constitutes the
engine of scientific progress. In biomedical research and in clinical practice we
assisted during the last decades to many overturnings or reversals of concepts
and practices. This phenomenon may discourage patients from accepting ordinary
medical care and may favour the choice of alternative medicine. The media often
enhance the disappointment for these discrepancies. In this note I recommend to
transfer to patients the concept of a confirmed and dependable knowledge at the
present time. However, physicians should tolerate uncertainty and accept the idea
that medical concepts and applications are subjected to continuous progression,
change and displacement.
PMID- 28408070
TI - Cell Death Pathway That Monitors Spore Morphogenesis.
AB - The use of quality control mechanisms to stall developmental pathways or
completely remove defective cells from a population is a widespread strategy to
ensure the integrity of morphogenetic programs. Endospore formation (sporulation)
is a well conserved microbial developmental strategy in the Firmicutes phylum
wherein a progenitor cell that faces starvation differentiates to form a dormant
spore. Despite the conservation of this strategy, it has been unclear what
selective pressure maintains the fitness of this developmental program, composed
of hundreds of unique genes, during multiple rounds of vegetative growth when
sporulation is not required. Recently, a quality control pathway was discovered
in Bacillus subtilis which monitors the assembly of the spore envelope and
specifically eliminates, through cell lysis, sporulating cells that assemble the
envelope incorrectly. Here, we review the use of checkpoints that govern the
entry into sporulation in B. subtilis and discuss how the use of regulated cell
death pathways during bacterial development may help maintain the fidelity of the
sporulation program in the species.
PMID- 28408072
TI - Nonmedical Use of Prescription Opioids among Pregnant U.S. Women.
AB - OBJECTIVES: Nonmedical use of opioids during pregnancy is associated with adverse
outcomes for women and infants, making it a prominent target for prevention and
identification. Using a nationally representative sample, we determined
characteristics of U.S. pregnant women who reported prescription opioid misuse in
the past year or during the past month. METHODS: We used data from the National
Survey on Drug Use and Health (2005-2014) in a retrospective analysis. The sample
included 8,721 (weighted n = 23,855,041) noninstitutionalized women, ages 12 to
44, who reported being pregnant when surveyed. Outcomes were nonmedical use of
prescription opioid medications during the past 12 months and during the past 30
days. Multivariable logistic regression models were created to determine
correlates of nonmedical opioid use after accounting for potential confounding
variables. RESULTS: Among pregnant women in the United States, 5.1% reported
nonmedical opioid use in the past year. In adjusted models, depression or anxiety
in the past year was strongly associated with past year nonmedical use (adjusted
odd ratio [AOR], 2.15; 95% CI, 1.52-3.04), as were past year use of alcohol (AOR,
1.56; 95% CI, 1.11-2.17), tobacco (AOR, 1.72; 95% CI, 1.17-2.53), and marijuana
(AOR, 3.44; 95% CI, 2.47-4.81). Additionally, 0.9% of U.S. pregnant women
reported nonmedical opioid use in the past month. Past year depression or anxiety
and past month use of alcohol, tobacco, and marijuana each independently
predicted past month nonmedical use. CONCLUSIONS: Characteristics associated with
nonmedical opioid use by pregnant women reveal populations with mental illness
and co-occurring substance use. Policy and prevention efforts to improve
screening and treatment could focus on the at-risk populations identified in this
study.
PMID- 28408073
TI - Pre-procedural peripheral endothelial function is associated with increased serum
creatinine following percutaneous coronary procedure in stable patients with a
preserved estimated glomerular filtration rate.
AB - BACKGROUND: Worsening renal function, indicated by increased serum creatinine
(SCr), is a common complication of percutaneous coronary procedures. Risk factors
for increased SCr overlap with coronary risk factors involved in endothelial
dysfunction. We hypothesized that endothelial dysfunction, measured using the
reactive hyperemia peripheral arterial tonometry index (RHI), can predict
periprocedure-increased SCr. METHODS: RHI was assessed before elective coronary
procedures in 316 consecutive stable patients with a preserved estimated
glomerular filtration rate (eGFR, >60mL/min/1.73m2). SCr was measured before and
2 days after procedures. RESULTS: There was no significant correlation between
natural logarithmic transformations of RHI (Ln-RHI) and basal Ln-eGFR.
Periprocedure increase in SCr was observed in 148 (47%) patients. The increased
SCr group had significantly lower Ln-RHI [0.48 (0.36, 0.62) vs. 0.59 (0.49,
0.76), p<0.001]. Multivariate linear regression analysis identified body mass
index (BMI) (beta=0.148, p=0.005) and Ln-RHI (beta=-0.365, p<0.001) as
significant determinants of percent changes in SCr. Multivariate logistic
regression analysis identified Ln-RHI (per 0.1) [odds ratio (OR) 0.672, 95%
confidence interval (95% CI) 0.586-0.722; p<0.001], Ln-B-type natriuretic peptide
(OR: 1.484, 95% CI: 1.130-1.974; p=0.004), current smoking (OR: 2.563, 95% CI:
1.379-4.763, p=0.003), BMI (OR: 1.113, 95% CI: 1.031-1.203; p=0.007), coronary
intervention (OR: 1.736, 95% CI: 1.036-2.909; p=0.036), and Ln-hemoglobin A1c
(OR: 6.728, 95% CI: 1.093-41.392, p=0.040) as independent determinants of
increased SCr. Receiver-operating characteristics curve analysis showed that Ln
RHI correlated significantly with increased SCr (area under the curve, 0.684, 95%
CI: 0.626-0.742, p<0.001). The optimum cut-off point of Ln-RHI for the
periprocedure increased SCr was 0.545. CONCLUSIONS: Pre-procedure measurement of
endothelial function by RHI is an effective strategy to assess the patient's risk
conditions for worsening renal function after percutaneous coronary procedures.
PMID- 28408074
TI - Burnout and job satisfaction of intensive care personnel and the relationship
with personality and religious traits: An observational, multicenter, cross
sectional study.
AB - OBJECTIVES: To investigate if burnout in the Intensive Care Unit (ICU) is
influenced by aspects of personality, religiosity and job satisfaction. RESEARCH
METHODOLOGY: Cross-sectional study, designed to assess burnout in the ICU and to
investigate possible determinants. Three different questionnaires were used: the
Malach Burnout Inventory, the Eysenck Personality Questionnaire and the
Spiritual/Religious Attitudes Questionnaire. Predicting factors for high burnout
were identified by multivariate logistic regression analysis.
SETTING/PARTICIPANTS: This national study was addressed to physicians and nurses
working full-time in 18 Greek ICU departments from June to December 2015.
RESULTS: The participation rate was 67.9% (n=149) and 65% (n=320) for ICU
physicians and nurses, respectively). High job satisfaction was recorded in both
doctors (80.8%) and nurses (63.4%). Burnout was observed in 32.8% of the study
participants, higher in nurses compared to doctors (p<0.001). Multivariate
analysis revealed that neuroticism was a positive and extraversion a negative
predictor of exhaustion (OR 5.1, 95%CI 2.7-9.7, p<0.001 and OR 0.49, 95%CI 0.28
0.87, p=0.014, respectively). Moreover, three other factors were identified: Job
satisfaction (OR 0.26, 95%CI 0.14-0.48, p<0.001), satisfaction with current End
of-Life care (OR 0.41, 95%CI 0.23-0.76, p=0.005) and isolation feelings after
decisions to forego life sustaining treatments (OR 3.48, 95%CI 1.25-9.65,
p=0.017). CONCLUSIONS: Personality traits, job satisfaction and the way End-of
Life care is practiced influence burnout in the ICU.
PMID- 28408075
TI - Effect of hospital type on the treatment of acute appendicitis in teenagers.
AB - BACKGROUND: Teenagers receive appendicitis care at both adult and pediatric
facilities. The purpose of this study was to evaluate outcomes following
treatment of acute appendicitis in teenagers based on the type of hospital
facility. METHODS: Patients aged 13-17years with acute appendicitis who were
discharged from acute care hospitals from 2009 to 2014 were identified using a
statewide discharge dataset. Hospitals were classified as pediatric or adult and
outcomes were compared. RESULTS: There were 5585 patients treated in adult
hospitals and 1625 in pediatric hospitals. Fewer patients at adult hospitals had
complicated appendicitis (20.4% vs. 33.0%, p<0.01). Open appendectomy occurred
more often in adult hospitals compared to pediatric hospitals (12.6% vs. 6.0%,
p<0.01). Pediatric hospitals had higher rates of non-operative management (10%
vs. 3.4%, p<0.01) and percutaneous drain placement (1.2% vs. 0.4%, p<0.01).
Postoperative complication rates did not significantly differ between hospital
types. CONCLUSION: Most teenagers undergo appendectomy at adult facilities;
however, a greater proportion of younger patients and patients with complicated
appendicitis is treated at pediatric hospitals. Treatment at a freestanding
children's hospital results in lower rates of open procedures and no difference
in complications. Opportunities may exist to standardize care across treating
facilities to optimize outcomes and resource use. TYPE OF STUDY: Prognosis study.
LEVEL OF EVIDENCE: II.
PMID- 28408076
TI - Ultrasound-guided gastrostomy tube placement: A case series.
AB - PURPOSE: Gastrostomy tubes (G-tubes) can be placed utilizing a variety of
techniques. Here we present a case series to demonstrate feasibility of a novel
method, ultrasound-guided G-tube placement (USGTP). METHODS: All cases of USGTP
at our institution from September 2015-August 2016 were reviewed. Data included
demographics, operative time, complications, time to first feeding, and 30-day
readmissions. All steps of the procedure were carried out using ultrasound
guidance, resulting in placement of a low-profile G-tube. RESULTS: Twelve
patients underwent USGTP. Median age at operation was 2.6years (IQR 0.9-5.3) and
median weight 9.9kg (IQR 7.2-18.4). Median operative time was 27min. (IQR 20-44).
First feeding occurred 8.8+/-2.9h after the procedure. The second patient in the
series experienced the only operative complication. In this case, a linear probe
was used with insufficient gastric distension, resulting in placement of the tube
through a fold in the stomach wall. This was recognized and remedied
intraoperatively. This prompted successful technique modification for future
USGTPs. Only one patient was readmitted within 30days, and this was related to
urinary retention, an underlying problem. CONCLUSION: US-guided G-tube placement
appears initially to be safe, efficient and effective. Advantages include good
anatomical delineation, a single incision, initial placement of a low-profile G
tube, and avoidance of endoscopy, laparoscopy, and radiation. This report
illustrates feasibility of USGTP paving the way for further investigation and
comparison to other existing gastrostomy insertion methods. LEVEL OF EVIDENCE:
IV.
PMID- 28408077
TI - Does timing of gastroschisis repair matter? A comparison using the ACS NSQIP
pediatric database.
AB - BACKGROUND: There is no consensus on optimal timing of gastroschisis repair. The
2012-2014 ACS NSQIP Pediatric Participant Use Data File was used to compare
outcomes of primary versus staged gastroschisis repair. METHODS: Cases were
divided into primary repair (0-1day) and staged repair (4-14days). Baseline
characteristics and outcomes were compared for primary versus staged closure
using Fisher's exact tests for categorical variables and Wilcoxon rank-sum tests
for continuous variables. Length of stay was compared after controlling for
prematurity. RESULTS: There were 627 subjects included, with 364 neonates in the
primary group and 263 in the staged group. The primary group demonstrated shorter
hospital length of stay (LOS) (5.1days; p<0.001) and had less surgical site
infections (OR=0.27; p=0.003), but had longer ventilator days (1.9days; p<0.001).
Neonates in the primary repair group were less likely to be discharged home
versus transferred to another hospital (OR=0.24; p=0.006) and more likely to
require nutritional support at discharge (OR=1.74; p=0.034). No significant
differences were identified for mortality, readmissions, postoperative LOS,
sepsis or other outcomes. CONCLUSION: Staged repair of gastroschisis has longer
LOS attributed to preoperative timing, but less ventilator days. Outcomes for
these closure techniques are equivocal and support surgeons performing the
closure technique they are most experienced with. LEVEL OF EVIDENCE: III
(Treatment: retrospective comparative study).
PMID- 28408078
TI - Adoption of Radiation Technology Among Privately Insured Nonelderly Patients With
Cancer in the United States, 2008 to 2014: A Claims-Based Analysis.
AB - Despite enthusiasm for advanced radiation technologies, understanding of their
adoption in recent years is limited. The aim of this study was to elucidate
utilization trends of conventional radiation, intensity-modulated radiotherapy
(IMRT), brachytherapy, proton radiotherapy, stereotactic body radiotherapy
(SBRT), and stereotactic radiosurgery (SRS) using a large convenience sample of
irradiated patients with cancer identified from private insurance claims in the
United States. The unit of analysis was a claim corresponding to a fraction of
delivered radiotherapy from 2008 to 2014. Each claim was assigned a disease site
on the basis of the diagnosis code and a radiation technology on the basis of the
procedure code. In 2014, conventional radiation and IMRT constituted 56% and 39%
of all radiation treatment claims, respectively, while brachytherapy constituted
2%, proton radiotherapy 1%, SBRT 1%, and SRS <1%. Compared with the first quarter
of 2008, the proportional contribution of conventional radiation and
brachytherapy to all radiation claims each decreased by 16% in the fourth quarter
of 2014. In contrast, proportional contribution increased by 32% for IMRT, 83%
for proton radiotherapy, 124% for SRS, and 309% for SBRT. Prostate cancer
constituted 60% of all proton claims in 2008 but declined to 37% by 2014. SBRT
was used to treat a variety of disease sites, most commonly primary lung (25%),
prostate (12%), secondary bone (9%), and secondary lung (9%), in 2014. In this
claims-based analysis of younger patients with private insurance, conventional
radiation and IMRT were the most commonly used technologies from 2008 to 2014,
while SBRT showed the most robust growth over the study period.
PMID- 28408079
TI - [Sedation with dexmedetomidine on Klippel Feil Syndrome infant patient].
PMID- 28408080
TI - [Importance of using basic statistics adequately in clinical research].
AB - BACKGROUND AND OBJECTIVE: The inadequate use of basic statistics is the main
responsible for scientific article misinterpretation. The purpose of this review
article was to review some basic statistical topics to alert authors and readers
about the importance of basic statistics proper reporting. CONTENT: A
bibliographical and cross-sectional study was carried out,which analyzed
publications in books and articles in the following databases: SciELO (Scientific
Electronic Library Online) and PubMed (Available from the National Center for
Biotechnology Information). Medical research is not free from the risk of false
positive and false negative results due to the choice of statistical tests and
presence of small sample sizes. CONCLUSION: Understanding the correct use of
basic statistics leads to fewer errors in reporting the results of studies
performed and in the interpretation of their conclusions.
PMID- 28408081
TI - [Nondepolarizing muscle relaxant improves direct laryngoscopy view with no effect
on face mask ventilation].
AB - BACKGROUND: Difficult or impossible face mask ventilation complicated with
difficult tracheal intubation during anesthesia induction occurs in 0.4% of adult
anesthesia cases, possibly leading to life-threatening complications. Because of
such catastrophes, muscle relaxants have been recommended to be administered
after confirming adequate face mask ventilation without a solid scientific
validation of this principal. METHODS: In this observational study, the ease of
ventilation and the scores of direct laryngoscopy views before and after
administration of cisatracurium were assessed in ninety young healthy adults,
without anesthetic risks and without foreseen difficult intubation and who were
scheduled for general elective surgeries. RESULTS: Before muscle relaxation, 43
patients (48%) were Cormack Grade I, while the remaining 47 patients (52%) were
either Cormack Grade II (28 patients, 31%) or Cormack Grade II (19 patients,
21%). Following muscle relaxation with cisatracurium, the number of patients with
Cormack Grade I significantly increased from 43 patients (48%) to 65 patients
(72%) (p=0.0013). Only 1 patient out of 19 patients (5%) improved his Cormack
grade from Grade III to Grade I while 16 out 19 patients (84%) improved their
Cormack grade from Grade III to Grade II after the use of cisatracurium. The
quality of face mask ventilation did not differ with and without muscle relaxants
in all patients. CONCLUSION: The use of cisatracurium in healthy young adults
undergoing general elective surgeries with no anticipated difficult endotracheal
intubation had no effect on the quality of face mask ventilation despite
resulting in a quantifiable improvement in the laryngeal view.
PMID- 28408082
TI - Injury factors associated with discharge status from emergency room at two major
trauma hospitals in The Gambia, Africa.
AB - INTRODUCTION: Injuries are the leading cause of disability across all ages and
gender. In this study, we identified predictors of discharge status and
disability at discharge among patients who seek emergency room treatment.
MATERIALS AND METHODS: The study was conducted in two major trauma hospitals in
urban Gambia. 1905 patients participated in the study. 74.9% were males, and
25.1% were females. The study includes injured patients from all mechanisms.
However, patients' records without age, gender, injury mechanism, and deposition
from the emergency room were considered incomplete and excluded. We examined
distributions of injury by age, gender, mechanism, place of occurrence, intent,
primary body part injured, and primary nature of injury. We identified
demographic and injury characteristics associated with hospital admission
(compared to emergency department discharge) and discharge disability (any level
of disability compared with none). RESULTS: The leading mechanisms of injury were
road traffic (26.1%), struck by objects (22.1%), cut/pierce (19.2%), falls
(19.2%), and burns (5.4%). Injuries most commonly occurred in the home (36.7%)
and on the road (33.2%). For those aged 19-44, the proportion of injuries due to
assault was higher for females (35.9%) than males (29.7%). Males had increased
odds for admission (aOR=1.48 95% CI=1.15-1.91) and for disability (aOR=1.45; 95%
CI=1.06-1.99). Increased odds for admission were found for brain injuries,
fractures, large system injuries, and musculoskeletal injuries when compared with
soft tissue injuries. The highest odds for any level of discharge disability were
found for brain injuries, fractures, injuries from falls, burns, and road
traffic. CONCLUSIONS: Epidemiology of injuries in The Gambia is similar to other
low-income countries. However, the magnitude of cases and issues uncovered
highlights the need for a formal registry.
PMID- 28408084
TI - Semiextended approach for intramedullary nailing via a patellar eversion
technique for tibial-shaft fractures: Evaluation of the patellofemoral joint.
AB - Intramedullary nail fixation is a common treatment for tibial-shaft fractures,
and it offers a better functional prognosis than other conservative treatments.
Currently, the primary approach employed during intramedullary nail insertion is
the semiextended position is the suprapatellar approach, which involves a
vertical incision of the quadriceps tendon Damage to the patellofemoral joint
cartilage has been highlighted as a drawback associated with this approach. To
avoid this issue, we perform surgery using the patellar eversion technique and a
soft sleeve. This method allows the articular surface to be monitored during
intramedullary nail insertion. We arthroscopically assessed the effect of this
technique on patellofemoral joint cartilage. The patellar eversion technique
allows a direct view and protection of the patellofemoral joint without affecting
the patella. Thus, damage to the patellofemoral joint cartilage can be avoided.
PMID- 28408083
TI - Masquelet technique versus Ilizarov bone transport for reconstruction of lower
extremity bone defects following posttraumatic osteomyelitis.
AB - OBJECTIVE: This study was to compare the effectiveness of Masquelet technique
versus Ilizarov bone transport in the treatment of lower extremity bone defects
following posttraumatic osteomyelitis. PATIENTS AND METHODS: We retrospectively
reviewed 39 patients who had been treated at our department for lower extremity
bone defects following posttraumatic osteomyelitis. They were 30 males and 9
females with a mean age of 39.18 (range, 12-63 years). The infected bone defects
involved 26 tibias and 13 femurs. The mean length of the bone defects after
radical debridement was 6.76cm (range, 2.7-15.7cm). Masquelet technique (MT,
group A) was used in 20 patients and Ilizarov bone transport (IBT, group B) in 19
ones. The measurements were bone outcomes (union, deformity, infection and leg
length discrepancy) and functional outcomes (significant limping, joint
contracture, soft tissue dystrophy, pain and inactivity). RESULTS: The mean
follow-up after removal of the apparatus was 25.26 months (range, 14-51 months).
The mean finite fixator time was 10.15 months (range, 8-14 months) in group A
versus 17.21 months (range, 11-24 months) in group B. The bone outcomes were
similar between groups A and B [excellent (5 vs. 7), good (10 vs.9), fair (4 vs.
2) and poor (1 vs. 1)]; group A showed better functional outcomes than group B
[excellent (8 vs. 3), good (9 vs. 6), fair (3 vs. 8) and poor (0 vs. 2)].
CONCLUSIONS: In the treatment of segmental lower extremity bone defects following
posttraumatic osteomyelitis, both IBT and MT can lead to satisfactory bone
results while MT had better functional results, especially in femoral cases. IBT
should be preferred in cases of limb deformity and MT may be a better choice in
cases of periarticular bone defects.
PMID- 28408085
TI - Tallying the bills of mortality from air pollution.
PMID- 28408087
TI - Public Health Science conference: a call for abstracts.
PMID- 28408088
TI - Department of Error.
PMID- 28408086
TI - Estimates and 25-year trends of the global burden of disease attributable to
ambient air pollution: an analysis of data from the Global Burden of Diseases
Study 2015.
AB - BACKGROUND: Exposure to ambient air pollution increases morbidity and mortality,
and is a leading contributor to global disease burden. We explored spatial and
temporal trends in mortality and burden of disease attributable to ambient air
pollution from 1990 to 2015 at global, regional, and country levels. METHODS: We
estimated global population-weighted mean concentrations of particle mass with
aerodynamic diameter less than 2.5 MUm (PM2.5) and ozone at an approximate 11 km
* 11 km resolution with satellite-based estimates, chemical transport models, and
ground-level measurements. Using integrated exposure-response functions for each
cause of death, we estimated the relative risk of mortality from ischaemic heart
disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung
cancer, and lower respiratory infections from epidemiological studies using non
linear exposure-response functions spanning the global range of exposure.
FINDINGS: Ambient PM2.5 was the fifth-ranking mortality risk factor in 2015.
Exposure to PM2.5 caused 4.2 million (95% uncertainty interval [UI] 3.7 million
to 4.8 million) deaths and 103.1 million (90.8 million 115.1 million) disability
adjusted life-years (DALYs) in 2015, representing 7.6% of total global deaths and
4.2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to
ambient PM2.5 increased from 3.5 million (95% UI 3.0 million to 4.0 million) in
1990 to 4.2 million (3.7 million to 4.8 million) in 2015. Exposure to ozone
caused an additional 254 000 (95% UI 97 000-422 000) deaths and a loss of 4.1
million (1.6 million to 6.8 million) DALYs from chronic obstructive pulmonary
disease in 2015. INTERPRETATION: Ambient air pollution contributed substantially
to the global burden of disease in 2015, which increased over the past 25 years,
due to population ageing, changes in non-communicable disease rates, and
increasing air pollution in low-income and middle-income countries. Modest
reductions in burden will occur in the most polluted countries unless PM2.5
values are decreased substantially, but there is potential for substantial health
benefits from exposure reduction. FUNDING: Bill & Melinda Gates Foundation and
Health Effects Institute.
PMID- 28408090
TI - Further Evidence that EVAR with Suprarenal Fixation may be Associated with Renal
Injury.
PMID- 28408089
TI - Editor's Choice - Mid-term Outcomes of Endovenous Laser Ablation in Patients with
Active and Healed Venous Ulcers: A Follow-up Study.
AB - OBJECTIVES: The aim of this study was to assess the mid-term ulcer recurrence
rate in patients with healed or active venous ulcers treated with endovenous
laser ablation (EVLA) for incompetent superficial axial veins and to search for
possible risk factors for non-healing and recurrence. METHODS: Consecutive
patients treated with EVLA because of a healed or active venous ulcer between
2006 and 2013 were identified in the medical records and quality registry and
invited to follow-up, including clinical history, study examination, Duplex
ultrasound scanning, ankle brachial pressure, photoplethysmography, venous
clinical severity score (VCSS), and health related quality of life (HRQoL)
measured with EQ5D. Of 228 patients, 170 (195 legs) fulfilled the inclusion
criteria. Twenty patients were interviewed by phone, 27 were unreachable and 11
were excluded. Univariate and multivariate regression analyses were performed to
identify possible risk factors for recurrence. RESULTS: The mean follow-up time
was 41 months (range 14-89 months). The average age was 66.6 years (range 36-87
years). All 86 legs operated on for an active ulcer had this ulcer healed
sometime between the operation and the study examination, but thereafter it
recurred in 14 patients (16%). In 109 legs operated on for a healed ulcer, the
ulcer recurred in 17 legs (16%). Complications such as permanent sensory loss
were seen in 16 legs (8%) and deep venous thrombosis in two legs (1%). Thirty
legs (15%) were re-treated for superficial venous incompetence (SVI). Reduced
ankle mobility was a risk factor for recurrence in both univariate and
multivariate analysis (p=.048). CONCLUSIONS: These midterm results demonstrate
that endovenous laser ablation of SVI in patients with healed or active venous
ulcers achieves good healing and low ulcer recurrence rates, with a low rate of
complications and an acceptable re-intervention rate.
PMID- 28408091
TI - Accessory genetic content in Campylobacter jejuni ST21CC isolates from feces and
blood.
AB - Campylobacter jejuni is an important foodborne pathogen and the most commonly
reported bacterial cause of gastroenteritis. C. jejuni is occasionally found in
blood, although mechanisms important for invasiveness have remained unclear. C.
jejuni is divided into many different lineages, of which the ST21 clonal complex
(CC) is widely distributed. Here, we performed comparative genomic and in vitro
analyses on 17C. jejuni ST21CC strains derived from human blood and feces in
order to identify features associated with isolation site. The ST21CC lineage is
divided into two large groups; centered around ST-21 and ST-50. Our clinical
strains, typed as ST-50, showed further microevolution into two distinct
clusters. These clusters were distinguished by major differences in their capsule
loci and the distribution of accessory genetic content, including C. jejuni
integrated elements (CJIEs) and plasmids. Accessory genetic content was more
common among fecal than blood strains, whereas blood strains contained a hybrid
capsule locus which partially consisted of C. jejuni subsp. doylei-like content.
In vitro infection assays with human colon cell lines did not show significant
differences in adherence and invasion between the blood and fecal strains. Our
results showed that CJIEs and plasmid derived genetic material were less common
among blood isolates than fecal isolates; in contrast, hybrid capsule loci,
especially those containing C. jejuni subsp. doylei-like gene content, were found
among many isolates derived from blood. The role of these findings requires more
detailed investigation.
PMID- 28408092
TI - The Relationship Between Serum Zinc Levels, Cardiac Markers and the Risk of Acute
Myocardial Infarction by Zinc Quartiles.
AB - BACKGROUND: Zinc is one of the most important microelements in the body and zinc
homeostasis plays a critical role in maintaining cellular structure and function.
Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease.
Our aim was to investigate whether there is a relationship between zinc and
cardiac markers, and the risk of acute myocardial infarction (AMI) by zinc
quartiles. METHODS: We enrolled a total of 529 patients and measured their serum
zinc levels and cardiac markers. We performed further studies after dividing
subjects into four groups according to their concentrations of zinc by quartile
to clarify the relationship between zinc levels and risk of increased acute
myocardial infarction prevalence rate. RESULTS: We observed that there was a
significant inverse linear relationship between zinc and Lg(creatine kinase)
(p=0.011), Lg(creatine kinase-MB) (p=0.002) and Lg(cardiac troponin T) (p=0.045).
In addition, the acute myocardial infarction prevalence rates were 28.8%, 24.8%,
20.5%, and 18.2% by patients with zinc quartiles, respectively. Multivariate
logistic regression analysis showed that the odds ratio between the lowest and
highest zinc quartile groups was 1.92 (1.019-3.604) (p<0.05). CONCLUSIONS: The
present study revealed a relationship between serum zinc levels in that zinc
levels were significantly inversely correlated with serum creatine kinase (CK),
creatine kinase-MB (CKMB) and cardiac troponin T (cTnT) levels. Furthermore, we
found that the prevalence rate of acute myocardial infarction decreased with
increasing zinc quartiles.
PMID- 28408093
TI - Myocardial Infarction Without Obstructive Coronary Artery Disease is Not a Benign
Condition (ANZACS-QI 10).
AB - BACKGROUND: Non-obstructive coronary artery disease (CAD) on coronary angiography
after myocardial infarction (MI) is associated with a lower risk of adverse
outcomes, but the prognosis may not be benign. Our aim was to assess outcomes in
MI with and without obstructive CAD, and in an age and sex matched comparison
cohort without known cardiovascular disease. METHODS: We performed a single
centre analysis of consecutive patients undergoing coronary angiography for MI
between 2007 and 2012. Patients were classified into those with obstructive CAD
(>=50% epicardial coronary artery stenosis) and those without obstructive CAD
(<50%). Myocardial infarction patient data was collected in an electronic
registry and linked anonymously to national hospitalisation and mortality
records. Age and sex matched patients without known CVD were identified from the
community PREDICT cohort. RESULTS: Of the 2070 patients with MI, 302 (15%) had
non-obstructive CAD. Compared to patients with obstructive disease they were
younger (mean 57 v 61 years, p<0.001), more likely to be women (50% vs 23%,
p<0.001), to be of Maori or Pacific vs. European ethnicity (p<0.001), more likely
to be lifelong non-smokers (46% v 38%, p=0.02), non-diabetic (80v 73%, p <0.01),
have no ST-segment deviation (78% v 46%, p<0.001), and have a low risk Global
Registry of Acute Coronary Events acute coronary syndrome (GRACE ACS) score (54 v
35%, p<0.001). They were also less likely to receive 'triple therapy' secondary
prevention medications (81% v 94%, p<0.0001). The cumulative two-year Kaplan
Maier composite outcome of mortality or non-fatal MI was 14.3% for MI with
obstructive CAD, 4.6% for MI without obstructive disease, and 2.2% for patients
without prior CVD (p<0.001). CONCLUSION: Myocardial infarction without
obstructive coronary disease is common (~1 in 7 patients) and is not clinically
benign, with an adverse outcome rate double that of age and sex matched patients
without CVD.
PMID- 28408094
TI - Factors associated with pharmacy students' attitudes towards learning
communication skills - A study among Nordic pharmacy students.
AB - INTRODUCTION: Good communication skills are essential for pharmacy students to
help patients with their medicines. Students' attitudes towards communication
skills learning will influence their willingness to engage in communication
training, and their skills when dealing with patients later on in their
professional life. OBJECTIVE: The aim of this study was to explore Nordic
pharmacy students' attitudes to communication skills learning, and the
associations between those attitudes and various student characteristics. METHOD
AND MATERIALS: A cross-sectional questionnaire-based study was conducted in 11
Nordic pharmacy schools between April 2015 and January 2016. The overall response
rate for the final study population was 77% (367 out of 479 students). Pharmacy
students who had fulfilled all mandatory communication training and most of their
pharmacy practical experience periods were included. The communication skills
attitudes scale was the main outcome. Linear regression models were fitted with
the outcome variable and various student characteristics as the predictors, using
generalized estimating equations to account for clustering within pharmacy
schools. RESULTS: Nordic pharmacy students in general have moderately positive
attitudes towards learning communication skills. Positive attitudes towards
learning communication skills among pharmacy students were associated with being
female (betaadjusted 0.42, 95% CI 0.20 to 0.63, p < 0.001), following a newer
pharmacy training program (betaadjusted 0.81, 95% CI 0.63 to 0.98, p < 0.001),
having higher self-rated need for communication skills improvement (betaadjusted
0.50, 95% CI 0.30 to 0.71, p<0.001) and believing one's communication skills are
not the result of personality (betaadjusted -0.24, 95% CI -0.44 to -0.04,
p=0.017). CONCLUSION: The study provides important information for faculty
members responsible for curriculum improvements and teachers to refine their
teaching of communication skills. From this, the teaching can be better tailored
to suit different students. The students' chances of being able to effectively
help patients in the future will be increased by that.
PMID- 28408095
TI - Scale-up and inhibitory studies on productivity of lipase from Acinetobacter
radioresistens PR8.
AB - Acinetobacter radioresistens PR8 produces extracellular lipase depending upon
growth media. In present work we not only screened the nutrient sources but also
investigated the causes for variation in productivity. The nutrient sources
investigated are, groundnut oil, groundnut cake and fresh groundnut. Lower lipase
productivity was observed on fresh ground nut in contrast to groundnut oil and
groundnut cake. The lipase productivity was examined in the batch and parameters
monitored were bacterial growth, enzyme activity, pH, lipids and protein
concentration. The aflatoxin B1 and oxalic acid present in fresh groundnut were
found to be responsible for lower lipase productivity. The interaction studies of
oxalic acid and purified lipase was confirmed with CD spectra analysis,
isothermal titration calorimetry studies and fluorescence quenching. Therefore,
the importance of economical cheap groundnut cake with no aflatoxin B1 and
oxalates are proposed to be used for optimum lipase production.
PMID- 28408096
TI - Local treatment of a pharyngocutaneous fistula secondary to osteoradionecrosis.
AB - Radionecrosis is a late, and difficult to treat,complication of radiotherapy
performed on head and neck tumours, and it is difficult to treat. This process
causes significant damage, not only in the skin, but also in muscular, nervous,
vascular, and bone structures. This, in turn, leads to airway and digestive tract
involvement, as well as a functional loss and a cosmetic defect that usually
requires reconstructive surgery. Therefore, this process is associated with a
significant loss in the quality of life of patients and involves a long hospital
stay for treatment, as well as the necessary support measures. This article
describes the local treatment of pharyngocutaneous fistula secondary to radiation
therapy of squamous cell carcinoma of the right oropharynx. The lesion appeared
two months after completing this treatment and required surgical reconstruction
with a myocutaneous flap to repair the tissue defect. In this context, an
alginate wound dressing with silver was used, combined with a medium grip
polyurethane foam with a silicone border. Within one month, there was autolytic
debridement of all the necrotic tissue and the appearance of granulation tissue.
At the same time, the infection was controlled, and a better management of the
exudate was obtained, which provided a suitable surgical bed for the
reconstruction.
PMID- 28408097
TI - Crisis in the health sector: Impact on nurses' working conditions.
AB - : In a context of economic crisis and policies to reduce the public deficit, the
budgets of the Catalan Health Institute (CHI) were cut by 15.33% between 2010 and
2014. OBJECTIVE: To assess the perceived impact on nurses' work conditions of
measures to contain health spending. METHOD: The study design was descriptive and
transversal. A sample of 1,760 nurses from the province of Barcelona answered a
questionnaire on the perceived impact of health spending containment measures
implemented in their workplace during the early years of the crisis. RESULTS:
Among the main aspects of the perceived impact of these measures, 86.6% of the
nurses identified a pay cut and an increase in the following relevant parameters
of their working conditions: number of hours worked (66.7%), final ratio of
treated patients (35.2%), task complexity and workload (75.3%), rotation through
various departments (31.5%), work shifts (21.4%) or work areas (23.4%), job
insecurity (58.4%) and loss of employment by dismissal (6.6%) or non-renewal of
contract (9%). CONCLUSIONS: The perceived impact of the crisis showed a triple
negative component: Pay cut, work overload and job insecurity. As a combined
effect of this multiple trend, the nurses acknowledged a deterioration in their
working conditions and quality of working life.
PMID- 28408098
TI - Population genetics of the Schistosoma snail host Bulinus truncatus in Egypt.
AB - The tropical freshwater snail Bulinus truncatus serves as an important
intermediate host of several human and cattle Schistosoma species in many African
regions. Despite some ecological and malacological studies, there is no
information on the genetic diversity of B. truncatus in Egypt. Here, we sampled
70-100 snails in ten localities in Upper Egypt and the Nile Delta. Per locality,
we sequenced 10 snails at a partial fragment of the cytochrome c oxidase subunit
1 gene (cox1) and we genotyped 25-30 snails at six microsatellite markers. A
total of nine mitochondrial haplotypes were detected, of which five were unique
to the Nile Delta and three were unique to Upper Egypt, indicating that snail
populations may have evolved independently in both regions. Bayesian clustering
and hierarchical F-statistics using microsatellite markers further revealed
strong population genetic structure at the level of locality. Observed
heterozygosity was much lower compared to what is expected under random mating,
which could be explained by high selfing rates, population size reductions and to
a lesser extent by the Wahlund effect. Despite these observations, we found
signatures of gene flow and cross-fertilization, even between snails from the
Nile Delta and Upper Egypt, indicating that B. truncatus can travel across large
distances in Egypt. These observations could have serious consequences for
disease epidemiology, as it means that infected snails from one region could
rapidly and unexpectedly spark a new epidemic in another distant region. This
could be one of the factors explaining the rebound of human Schistosoma
infections in the Nile Delta, despite decades of sustained schistosomiasis
control.
PMID- 28408099
TI - The sexuality of young women with intellectual and developmental disabilities: A
neglected focus in the American foster care system.
AB - Youths with intellectual and developmental disabilities (ID/DD) are
overrepresented in the American foster care system and experience heightened
rates of pregnancy compared to their nondisabled peers. Yet limited information
is known about sexually active or pregnant young women with ID/DD in foster care.
Consequently, important healthcare needs of this population are not adequately
addressed. This article explores sexuality education and sexual healthcare for
female adolescents in foster care with ID/DD and recommends practice guidelines
to support and prepare their emergent sexual development.
PMID- 28408100
TI - In reply to "Acute respiratory distress secondary to blood transfusion".
PMID- 28408101
TI - A new technique for accelerated liver regeneration: An experimental study in
rats.
AB - BACKGROUND: Associating liver partition and portal vein ligation for staged
hepatectomy (ALPPS) is used to accelerate growth of the future liver remnant. We
investigated alternative methods for increasing the future liver remnant.
METHODS: A total of 152 rats were randomized as follows: (1) sham; (2) portal
vein ligation; (3) portal vein ligation/surgical split (ALPPS); (4) portal vein
ligation/split of the liver with a radiofrequency ablation needle; (5) portal
vein ligation/radiofrequency ablation of the deportalized liver (portal vein
ligation/radiofrequency ablation necrosis in the deportalized liver); (6) portal
vein ligation/radiofrequency ablation of the future liver remnant (portal vein
ligation/radiofrequency ablation-future liver remnant); and (7) controls. Animals
were evaluated on postoperative days 2 and 4. Bodyweight, liver parameters,
hepatic regeneration rate, proinflammatory cytokines, hepatocyte proliferation,
and gene expression were measured. RESULTS: Hepatic regeneration rate indicated a
steady increase in all intervention groups compared with sham rats (P < .001). At
postoperative day 2, the hepatic regeneration rate was significantly higher in
the portal vein ligation/radiofrequency ablation necrosis in the deportalized
liver group than in the portal vein ligation group (P = .039). On postoperative
day 4, we found significant differences between the portal vein ligation group
and the ALPPS (P = .015), portal vein ligation/split of the liver with a
radiofrequency ablation needle (P = .010), and portal vein
ligation/radiofrequency ablation necrosis in the deportalized liver (P = .046)
groups. Hepatocyte proliferation was significantly higher at all times compared
with sham rats. On postoperative day 4, we found a significantly higher
proliferation in groups 3, 4, 5, and 6 compared to portal vein ligation. Gene
analysis revealed upregulation of genes involved in cellular proliferation and
downregulation of genes involved in cellular homeostasis in all intervention
groups. Between the intervention groups, gene expression was nearly identical.
Biochemical markers and proinflammatory cytokines were comparable between groups.
CONCLUSION: The surplus liver regeneration after ALPPS is probably mediated
through parenchymal damage and subsequent release of growth stimulators, which
again upregulates genes involved in cellular regeneration and downregulates genes
involved in cellular homeostasis. We also demonstrate that growth of the future
liver remnant, comparable to that seen after ALPPS, could be achieved by
radiofrequency ablation treatment of the deportalized liver, that is, a procedure
in which the initial step in humans can be performed percutaneously.
PMID- 28408102
TI - Exploring data sources for road traffic injury in Cameroon: Collection and
completeness of police records, newspaper reports, and a hospital trauma
registry.
AB - BACKGROUND: Road traffic injury surveillance systems are a cornerstone of
organized efforts at injury control. Although high-income countries rely on
established trauma registries and police databases, in low- and middle-income
countries, the data source that provides the best collection of road traffic
injury events in specific low- and middle-income country contexts without mature
surveillance systems is unclear. The objective of this study was to compare the
information available on road traffic injuries in 3 data sources used for
surveillance in the sub-Saharan African country of Cameroon, providing potential
insight on data sources for road traffic injury surveillance in low- and middle
income countries. We assessed the number of events captured and the information
available in Yaounde, Cameroon, from 3 separate sources of data on road traffic
injuries: trauma registry, police records, and newspapers. METHODS: Data were
collected from a single-hospital trauma registry, police records, and the 6 most
widely circulated newspapers in Yaounde during a 6-month period in 2009. The
number of road traffic injury events, mortality, and other variables included
commonly in injury surveillance systems were recorded. We compared these sources
using descriptive analysis. RESULTS: Hospital, police, and newspaper sources
recorded 1,686, 273, and 480 road traffic injuries, respectively. The trauma
registry provided the most complete data for the majority of variables explored;
however, the newspaper data source captured 2, mass casualty, train crash events
unrecorded in the other sources. Police data provided the most complete
information on first responders to the scene, missing in only 7%. CONCLUSION:
Investing in the hospital-based trauma registry may yield the best surveillance
for road traffic injuries in some low- and middle-income countries, such as
Yaounde, Cameroon; however, police and newspaper reports may serve as alternative
data sources when specific information is needed.
PMID- 28408103
TI - Effect of CPAP on diastolic function in coronary artery disease patients with
nonsleepy obstructive sleep apnea: A randomized controlled trial.
AB - BACKGROUND: Obstructive sleep apnea (OSA) has been associated with worse
diastolic function in patients with coronary artery disease (CAD). This analysis
determined whether continuous positive airway pressure (CPAP) treatment would
improve diastolic function in CAD patients with nonsleepy OSA. METHODS: Between
December 2005 and November 2010, 244 revascularized CAD patients with nonsleepy
OSA (apnea-hypopnea index (AHI) >=15/h, Epworth Sleepiness Scale [ESS] score<10)
were randomly assigned to CPAP or no-CPAP. Echocardiographic measurements were
obtained at baseline, and after 3 and 12months. RESULTS: A total of 171 patients
with preserved left ventricular ejection fraction (>=50%), no atrial fibrillation
or severe valve abnormalities, and technically adequate echocardiograms at
baseline and follow-up visits were included (CPAP, n=87; no-CPAP, n=84). In the
intention-to-treat analysis, CPAP had no significant effect on echocardiographic
parameters of mild (enlarged left atrium or decreased diastolic relaxation
velocity) or worse (increased E/e filling index [presumed elevated left
ventricular filling pressure]) diastolic function. Post-hoc analysis revealed a
significant association between CPAP usage for >=4h/night and an increase in
diastolic relaxation velocity at 12months' follow-up (odds ratio 2.3, 95%
confidence interval 1.0-4.9; p=0.039) after adjustment for age, sex, body mass
index, and left atrium diameter at baseline. CONCLUSIONS: CPAP did not improve
diastolic dysfunction in CAD patients with nonsleepy OSA. However, good CPAP
adherence was significantly associated with an increase in diastolic relaxation
velocity after one year.
PMID- 28408104
TI - Long-term treatment with ivabradine over 12months in patients with chronic heart
failure in clinical practice: Effect on symptoms, quality of life and
hospitalizations.
AB - BACKGROUND: Ivabradine is indicated to control heart rate in otherwise optimally
treated patients with chronic heart failure (CHF) and reduced ejection fraction.
However, data on its effectiveness outside clinical trials and longer-term
effects are scarce. METHODS: We performed a prospective cohort study involving
249 German resident cardiologists and analyzed the 1-year effectiveness and
safety of ivabradine used in CHF outpatients. Data on symptoms, quality of life,
and hospitalizations were collected. RESULTS: In total, 767 CHF patients were
enrolled to receive ivabradine twice daily, of whom 684 (90%) were still on
ivabradine at study end (mean treatment duration 11.2months). The cohort was
representative of CHF patients seen in clinical practice in terms of age, risk
factor profile, and comorbidities. Concomitant beta-blocker therapy was
prescribed in 497 patients (65%). After one year, compared to baseline, heart
rate in ivabradine-treated patients was 16bpm lower. This reduction was
associated with a significant improvement in NYHA class, and less frequent signs
of decompensation (36% to 8%). The proportion of hospitalized patients within
1year decreased from 23% before treatment, to 5% with ivabradine therapy. These
improvements in clinical status were accompanied by a reduction in BNP and an
increase in LVEF (+5.1% at 1year). Quality of life was significantly improved in
all measured dimensions. Adverse drug reactions were noted in 26 patients (3%),
and were in line with the known safety profile of ivabradine. CONCLUSIONS:
Ivabradine was effective and well-tolerated in CHF patients seen in clinical
practice throughout 1year of treatment.
PMID- 28408105
TI - A meta-analysis of effects of transcatheter versus surgical aortic valve
replacement on left ventricular ejection fraction and mass.
AB - OBJECTIVES: To determine which procedure, transcatheter aortic valve implantation
(TAVI) or surgical aortic valve replacement (SAVR), for severe aortic stenosis
(AS) improves follow-up left ventricular (LV) function or hypertrophy more
effectively, we performed the first meta-analysis of comparative studies
reporting LV ejection fraction (LVEF) or mass (LVM) after TAVI versus SAVR.
METHODS: Studies considered for inclusion met the following criteria: the article
was written in English; the design was a comparative study; the study population
was patients with severe AS; patients were assigned to TAVI versus SAVR; and
outcomes included follow-up (6-12-month) LVEF or LVM. For each study, data
regarding fractional changes in LVEF or LVM in both the TAVI and SAVR groups were
used to generate mean differences (MDs) and 95% confidence intervals (CIs).
RESULTS: Our search identified 8 eligible studies. Two studies with baseline
LVEF<40% demonstrated significantly greater fractional changes in LVEF after TAVI
than after SAVR. A pooled analysis of 6 studies demonstrated no statistically
significant difference in fractional changes in LVEF between TAVI and SAVR (MD,
3.25%; 95% CI, -1.30% to 7.80%; p=0.16). Another pooled analysis of 5 studies
demonstrated significantly greater fractional changes (i.e. less fractional
"reductions") in LVM after TAVI than after SAVR (MD, 4.75%; 95% CI, 2.18% to
7.32%; p=0.0003). CONCLUSIONS: For patients with severe AS, SAVR may be
associated with greater improvement in LVM, probably not in LVEF, at 6-12 months.
For limited patients with reduced LVEF, TAVI might be associated with greater
improvement in LVEF.
PMID- 28408106
TI - Induced pluripotent stem cell technology: Toward the future of cardiac
arrhythmias.
AB - The development of human induced pluripotent stem cell (iPSC) technology has
revitalized the efforts made in the last decade to exploit the potential of human
embryonic stem cells (ESCs) for scientific research. In the field of cardiac
arrhythmias, the possibility of generating an unlimited amount of patient
specific cardiomyocyte-like cells (iPSC-CMs) has clear advantages compared with
the use of ESC-derived cardiac cells. In particular, with the introduction and
implementation of the large-scale precision medicine initiative, we anticipate
that the iPSC technology will play an important role in the advancement of
cardiovascular research and medicine. This platform is not free from technical
limitations that must be carefully taken into account; however, the utility of
iPSC-CMs in disease modeling and drug testing studies is hardly questionable.
Here, we summarize some of the progresses made in the field of iPSC technology
applied to inherited cardiac arrhythmias, with particular emphasis on the use of
iPSC-CMs for modelling the long QT syndrome and for the development of
personalized drug and molecular therapies. The growing role of iPSC technology in
the practice of precision medicine will also be discussed.
PMID- 28408107
TI - Hydroxyurea for nontransfusion-dependent beta-thalassemia: A systematic review
and meta-analysis.
AB - OBJECTIVE/BACKGROUND: Nontransfusion-dependent beta-thalassemia (NTDbetaT)
syndromes consist of beta-thalassemia intermedia and moderate hemoglobin E/beta
thalassemias. They are characterized by varying degrees of chronic anemia and a
wide spectrum of complications due to ineffective erythropoiesis and iron
overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic
drug, is anticipated to decrease disease severity. METHODS: We performed a meta
analysis to evaluate the clinical efficacy and safety of HU in NTDbetaT patients
of any age. MEDLINE, EMBASE, Cochrane databases, and major conference proceedings
for studies that assessed HU in NTDbetaT patients were searched. Qualities of
eligible studies were assessed by National Institutes of Health tools. RESULTS:
Seventeen studies, collectively involving 709 patients, fulfilled the eligibility
criteria. HU was associated with a significant decrease in transfusion need in
severe NTDbetaT with complete and overall (>=50%) response rates of 42% and 79%,
respectively. For mild NTDbetaT, HU was effective in raising hemoglobin by 1g/L
in 64% of patients. CONCLUSION: HU appears to be effective, well tolerated, and
associated with mild and transient adverse events. NTDbetaT patients may benefit
from a trial of HU, although large randomized clinical trials assessing its
efficacy should be conducted to confirm the findings of this meta-analysis and to
assess its long-term toxicity and response sustainability.
PMID- 28408108
TI - Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based
dosing in hematopoietic stem cell transplant patients.
AB - Busulfan (Bu)-based preparative regimens in hematopoietic stem cell
transplantation are commonly used. Previous studies have shown that Bu at a fixed
dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug
pharmacokinetics and this decreases the dependency on therapeutic drug monitoring
(TDM) of Bu. We compared the Bu dose given using TDM with the FBD of
3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic
myeloid leukemia, thalassemia major, and sickle cell disease were included. The
mean age at transplant was 15years (range 2-55years) with 57% adults. Indication
for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients,
while the remaining 54% were transplanted for inherited blood disorders. We found
that the median FBD was lower than the median TDM dose by 39mg/day with a
statistically significant difference (p<0.001) even after adjusting for the
weight (median total FBD of 349mg, median TDM dose of 494mg, p<0.0001). Age and
underlying condition (malignant vs. nonmalignant) were the main factors affecting
Bu clearance (p<0.001 and p<0.07, respectively). TDM remains an important tool
for the appropriate dosing of Bu in preparative regimens of hematopoietic stem
cell transplantation, especially in populations with genetic admixture.
PMID- 28408109
TI - Investigation of a suspected outbreak of lipoatrophia semicircularis in children.
AB - BACKGROUND AND OBJECTIVE: Recent reports of outbreaks of lipoatrophia
semicircularis (LS) in various countries have generated discussion regarding the
potential role of the environmental characteristics of office workplaces in new
buildings. The objective of this study was to investigate a suspected outbreak of
LS among children in a public school in Barcelona, which generated tremendous
alarm. METHODS: We performed an epidemiological assessment including descriptive
and prevalence analyses, and an environmental investigation followed by a
psychiatric assessment according to Small's criteria. We compared the prevalence
of LS and its 95% confidence interval between children and staff attending the
day-care centre under study and other centres. RESULTS: Among 86 children
attending a day-care centre we detected 11 confirmed and 2 possible cases of LS
(15.1%) while among 41 children attending other day-care centres we identified 8
cases and 4 possible cases (29.3%) (P=.10). Among 12 day-care staff, we detected
8 cases of LS (66.7%) while among 19 women working different jobs we identified
14 with the same condition as the staff (73.7%) (P=.98). All lesions were finally
classified as indentations with different locations. The environmental evaluation
didn't identify any exposure factors with a significant role in the onset of the
outbreak. The outbreak shared 13 of Small's 16 criteria regarding epidemic
somatoform disorder ("mass hysteria"). CONCLUSION: The presence of indentations
can be considered a normal variant in the lower extremities of children. The
characteristic development of the process leads us to the conclusion that this
outbreak was an epidemic somatoform disorder.
PMID- 28408110
TI - Evaluation of the activity of rheumatoid arthritis in clinical practice.
Agreement between self-rated clinimetric evaluation and clinical evaluation with
activity indexes: DAS28, CDAI and SDAI.
AB - INTRODUCTION AND OBJECTIVE: To achieve control of rheumatoid arthritis (RA) it is
necessary to be able to evaluate its activity. The American College of
Rheumatology (ACR) recommends for this purpose indexes of activity that can be
performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation
with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective
was to analyze the concordance between self-rated clinimetric evaluation and
clinimetric evaluation performed by the physician. PATIENTS AND METHOD:
Analytical cross-sectional study in 126 patients with RA. The agreement was
evaluated through the weighted kappa coefficient and the Krippendorff's alpha
coefficient. RESULTS: The PAS-II and RAPID-3 significantly correlated with all
variables included in the core set of measures recommended by the ACR/EULAR. The
agreement between PAS-II and CDAI-SDAI was good (kappa: 0.6, alpha: 0.61-0.62),
and moderate with DAS28-ESR (kappa: 0.53, alpha: 0.56). The concordance between
RAPID-3 and CDAI-SDAI was moderate (kappa: 0.55-0.57, alpha: 0.50-0.51), and
moderate with DAS28-ESR (kappa: 0.55, alpha: 0.53). When categorizing the
activity in remission/low activity vs. moderate/severe activity, the agreement
was greater with the PAS-II (0.59 vs. 0.34; P=.012). CONCLUSION: The good
concordance between PAS-II and SDAI supports their use in clinical practice,
especially if biomarkers of inflammation or the possibility of joint count are
not available. However, in order to recommend its routine application in clinical
practice, it is necessary to perform longitudinal studies that assess its
responsiveness.
PMID- 28408111
TI - Management of PET diagnosed thyroid incidentalomas in British Columbia Canada:
Critical importance of the PET report.
AB - BACKGROUND: PET diagnosed thyroid incidentalomas (TI) should undergo prompt
evaluation due to a high risk of underlying malignancy. Our study reviewed
physician management of PET diagnosed TIs in British Columbia (BC), Canada.
METHODS: All PET reports from BC between 2011 and 2014 were reviewed. Clinical
and demographic data was obtained for TI patients through chart review and mail
out surveys to physicians. Statistical analysis was performed to identify factors
associated with further TI investigation. RESULTS: 4.7% PET scans diagnosed TIs
in 5.3% of patients. 9.8% of diffuse and 46.1% of focal TI cases underwent
ultrasound +/- biopsy. PET scan report characteristics were significantly
associated with further TI investigation (p-value <0.05). CONCLUSIONS: Patients
with PET diagnosed TIs are being under-investigated in BC and PET scan report
related factors were found to be significantly associated with undergoing further
TI workup.
PMID- 28408112
TI - Outcome comparisons between high-volume robotic and laparoscopic surgeons in a
large healthcare system.
AB - Robotic colorectal surgery has been performed for nearly a decade, but has been
criticized for high cost. We sought to assess outcomes of colorectal operations
performed by surgeons with higher experience in robotics and laparoscopy across a
large health system. We performed a retrospective review of colon or rectal
resections performed between January 2013 and May 2016 within the Providence
Health and Services. Surgeons were only included if they performed 30 or more
procedures with an approach per year. We assessed outcomes including operative
time, hospital length of stay, complications, readmission, conversion to open
rates and total direct costs. When comparing the two groups, robotics surgery had
a decreased length of hospital stay, lower conversion rate, and longer operative
time. There was no statistical difference between complications and rate of
readmission. There was no statistically significant difference in total direct
cost. These data do suggest that high volume robotic surgery can carry the
benefit of a lower length of stay and lower conversion rate, while not incurring
an increase in total cost, complication or readmissions.
PMID- 28408113
TI - Surgical outcomes in women >=70 years undergoing mastectomy with and without
reconstruction for breast cancer.
AB - BACKGROUND: Approximately 4% of women age 70 will develop breast cancer during
the next ten years. Reconstruction has become a standard option for young women
undergoing mastectomy for breast cancer, however may not be offered to older
women due to the presence of co-morbidities. There is limited data on the
outcomes of mastectomy with reconstruction in patient's >= 70. This study
examines comorbidities and 30-day complication rates in patients >=70 undergoing
mastectomy for breast cancer. METHODS: The American College of Surgeons National
Surgery Quality Improvement Program database was used to examine co-morbidities
and 30-day complication rates in breast cancer patients undergoing mastectomy
from 2007 to 2012. Patients were grouped based on age and procedure. Complication
rates were characterized using descriptive statistics and Wilcoxon rank sum-test.
Variable frequencies were compared using Chi-square or Fisher's exact test.
RESULTS: 54,821 patients underwent mastectomy. Among patients >=70, 11,927 did
not have reconstruction, 109 had reconstruction. Among patients <70, 40,755 did
not have reconstruction and 2040 had reconstruction. Patients without
reconstruction had a significantly higher number of co-morbidities compared to
those having reconstruction (P = 0.001). The 30-day complication rate for
patients without reconstruction was 4.2% in patients >=70 compared to 4.4% for
those <70 (p = 0.4). In patients with reconstruction, the 30-day complication
rate was 6.4% in patients >=70 compared to 5.6% for those <70 (p = 0.7).
CONCLUSION: There was no difference in 30-day complication rate between patients
>=70 and < 70 having mastectomy with and without reconstruction. Similar outcomes
among women >=70 years and younger patients undergoing reconstruction may reflect
patient selection based on co-morbidities. With appropriate risk stratification,
breast reconstruction may be a safe surgical option for women >=70 year patients
undergoing treatment for breast cancer.
PMID- 28408114
TI - [Comment to the article "The hability of family doctor detecting psychiatric
pathology"].
PMID- 28408115
TI - [Author's reply].
PMID- 28408116
TI - [Prevalence of oral anticoagulation and quality of its management in primary
healthcare: A study by the Health Sentinel Network of the Region of Valencia
(Spain)].
AB - OBJECTIVE: To estimate the prevalence of patients with oral anticoagulant therapy
(OAT) in the Region of Valencia and to evaluate the quality of management of OAT
with vitaminK antagonists (VKA) carried out in primary healthcare. DESIGN:
Observational cross-sectional study conducted through the Health Sentinel Network
of the Region of Valencia, which includes a survey and the retrospective analysis
of OAT monitoring. SETTING: Primary healthcare, Region of Valencia, Spain.
SUBJECTS: All patients aged 18years or older on OAT who consulted during the year
2014. The population covered by the 59 doctors of the Health Sentinel Network
constitutes 2.2% of the adult population of the Region of Valencia, and it is
representative of it. KEY MEASUREMENTS: Demographic, socioeconomic and health
data as well as information concerning OAT. Quality of OAT management with VKA
was assessed by means of the percentage of time in therapeutic range (TTR),
computed using the Rosendaal method. RESULTS: A total of 1,144 patients were
recorded (mean age 74.5+/-11 years; 49.7% women). Prevalence of OAT in the Region
of Valencia is 1.3 cases per 100 population. The characteristic profile of these
patients is an old person, with several comorbidities and a low level of
education, who lives accompanied. Atrial fibrillation is the most common
indication. 82.8% of patients on OAT with VKA were monitored in primary
healthcare. The average TTR was 65.0%, and 53.9% of patients had a TTR >=65%.
Among inadequately controlled patients, 74.4% were perceived as well-controlled
by their primary care doctor. CONCLUSIONS: Prevalence of OAT is high, and it is
expected to increase. The degree of control achieved meets the generally accepted
quality standard (mean TTR >=65%), and it is comparable to that observed in other
national and international studies. However, there is wide scope for improvement.
It is crucial to optimize the management of this therapy in the most effective
and cost-effective way. Among other measures, access of physicians to their
patients' clinical information should be improved.
PMID- 28408117
TI - [Development of the "Consensus guidelines for the use of drugs in renal
failure"].
PMID- 28408118
TI - A novel combined vaccine based on monochimeric VLP co-displaying multiple
conserved epitopes against enterovirus 71 and varicella-zoster virus.
AB - Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious
diseases that mainly affect infants and children, causing significant morbidity
annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively,
are the principal epidemic pathogens causing these two diseases. To investigate
the possibility of developing a novel combined vaccine to prevent chicken pox and
HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc
V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc)
carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a
varied tandem manner. The chimeric HBc can self-assemble into VLPs with these
three epitopes displayed on the surface of particles. Epitope-specific antibody
characterization suggested that HBc-V/1/2 elicits a balanced antibody response
toward these three epitopes, and no immune interference was observed between the
three epitopes. Importantly, the anti-HBc-V/1/2 sera could simultaneously
neutralize VZV and EV71 and cross-neutralize coxsackievirus A16 (CVA16), another
major pathogen causing HFMD. Moreover, the anti-HBc-V/1/2 sera protected neonatal
mice from lethal challenge of EV71 and CVA16. Collectively, our study not only
demonstrated that HBc-V/1/2 is a promising candidate combined vaccine for HFMD
and Chicken pox but also provides a novel strategy for the design of combined
vaccines.
PMID- 28408119
TI - Ecological validity of cost-effectiveness models of universal HPV vaccination: A
systematic literature review.
AB - BACKGROUND: The protective (herd) effect of the selective vaccination of pubertal
girls against human papillomavirus (HPV) implies a high probability that one of
the two partners involved in intercourse is immunised, hence preventing the other
from this sexually transmitted infection. The dynamic transmission models used to
inform immunisation policy should include consideration of sexual behaviours and
population mixing in order to demonstrate an ecological validity, whereby the
scenarios modelled remain faithful to the real-life social and cultural context.
The primary aim of this review is to test the ecological validity of the
universal HPV vaccination cost-effectiveness modelling available in the published
literature. METHODS: The research protocol related to this systematic review has
been registered in the International Prospective Register of Systematic Reviews
(PROSPERO: CRD42016034145). Eight published economic evaluations were reviewed.
RESULTS: None of the studies showed due consideration of the complexities of
human sexual behaviour and the impact this may have on the transmission of HPV.
DISCUSSION: Our findings indicate that all the included models might be affected
by a different degree of ecological bias, which implies an inability to reflect
the natural demographic and behavioural trends in their outcomes and,
consequently, to accurately inform public healthcare policy. In particular,
ecological bias have the effect to over-estimate the preference-based outcomes of
selective immunisation. A relatively small (15-20%) over-estimation of quality
adjusted life years (QALYs) gained with selective immunisation programmes could
induce a significant error in the estimate of cost-effectiveness of universal
immunisation, by inflating its incremental cost effectiveness ratio (ICER) beyond
the acceptability threshold. The results modelled here demonstrate the
limitations of the cost-effectiveness studies for HPV vaccination, and highlight
the concern that public healthcare policy might have been built upon incomplete
studies.
PMID- 28408120
TI - Quantifying population preferences around vaccination against severe but rare
diseases: A conjoint analysis among French university students, 2016.
AB - BACKGROUND: Several concepts are available to explain vaccine decision making by
individual and inter-individual factors, including risk perception, social
conformism and altruism. However, only a few studies have quantified the weight
of these determinants in vaccine acceptance. Using a conjoint analysis tool, we
aimed at eliciting preferences in a student population regarding vaccination
against a rare, severe and rapidly evolving hypothetical disease, similar to
meningococcal serogroup C meningitis or measles. METHODS: During March-May 2016,
we conducted an emailing survey among university students aged 18-24years (N=775)
in Rennes, France. Participants were asked to decide for or against immediate
vaccination in 24 hypothetical scenarios, containing various levels of four
attributes: epidemic situation, adverse events, information on vaccination
coverage, and potential for indirect protection. Data were analysed using random
effect estimator logit models. RESULTS: Participants accepted on average 52% of
scenarios and all attributes significantly impacted vaccination acceptance. The
highest positive effects were seen with an epidemic situation (OR 3.81, 95%-CI
3.46-4.19), 90% coverage in the community (3.64, 3.15-4.20) and potential for
disease elimination from the community (2.87, 2.53-3.26). Information on
"insufficient coverage" was dissuasive (vs. none of friends vaccinated: 0.65,
0.56-0.75). Controversy had a significantly greater negative effect than a
confirmed risk of severe adverse events (OR 0.05 vs. 0.22). In models including
participant characteristics, preference weights were unchanged, while trust in
health authorities and vaccination perceptions strongly influenced acceptance
themselves. The greatest significant variation of preference weights between
subgroups was observed with controversy among students using alternative medicine
daily (OR 0.28) and among students relying on scientific vaccine information (OR
0.02). CONCLUSIONS: Among young adults, potential for indirect protection and
factual information on coverage in the community and potential side effects
positively impact theoretical vaccine acceptance. Conjoint analyses should be
conducted to understand vaccine hesitancy in specific vaccination programs.
PMID- 28408121
TI - Effectiveness of live attenuated influenza vaccine and inactivated influenza
vaccine in children during the 2014-2015 season.
AB - BACKGROUND: A clinical study found that live attenuated influenza vaccine (LAIV)
was superior to inactivated influenza vaccine (IIV) against drifted A(H3N2)
viruses in children. During the 2014-2015 influenza season, widespread
circulation of antigenically and genetically drifted A(H3N2) viruses provided an
opportunity to evaluate subtype-specific vaccine effectiveness (VE) of
quadrivalent LAIV (LAIV4) and IIV in children. METHODS: Children (2-17years) with
febrile acute respiratory illness <5days' duration were enrolled at 4 outpatient
sites in the United States during the 2014-2015 influenza season. Nasal swabs
were tested for influenza by reverse transcription polymerase chain reaction;
vaccination dates were obtained from medical records or immunization registries.
VE was estimated using a test-negative design comparing odds of vaccination among
influenza cases and test-negative controls with adjustment for potential
confounders. RESULTS: Among 1696 children enrolled, 1511 (89%) were included in
the analysis. Influenza was detected in 427 (28%) children; 317 had influenza
A(H3N2) and 110 had influenza B. Most influenza isolates were characterized as a
drifted strain of influenza A(H3N2) or a drifted strain of B/Yamagata. For LAIV4,
adjusted VE was 50% (95% confidence interval [CI], 27-66%) against any influenza,
30% (95% CI, -6% to 54%) against influenza A(H3N2), and 87% (95% CI, 63-96%)
against type B. For IIV, adjusted VE was 39% (95% CI, 18-54%) against any
influenza, 40% (95% CI, 16-58%) against A(H3N2), and 29% (95% CI, -15% to 56%)
against type B. Odds of influenza for LAIV4 versus IIV recipients were similar
against influenza A(H3N2) (odds ratio [OR], 1.17; 95% CI, 0.73-1.86) and lower
against influenza B (OR, 0.18; 95% CI, 0.06-0.55). CONCLUSIONS: LAIV4 and IIV
provided similar protection against a new antigenic variant A(H3N2). LAIV4
provided significantly greater protection than IIV against a drifted influenza B
strain. ClinicalTrials.gov identifier: NCT01997450.
PMID- 28408122
TI - Quality, immunogenicity and stability of meningococcal serogroup ACWY-CRM197, DT
and TT glycoconjugate vaccines.
AB - A physicochemical and immunological study of the stability of three different
meningococcal (Men) ACWY conjugate vaccines was performed to evaluate any
patterns of serogroup oligo- or polysaccharide-specific or carrier protein
specific stability that would affect immunogenicity. Critical quality and
stability-indicating characteristics were measured, with the study supporting the
suitability of both HPLC-SEC and HPAEC-PAD methods to detect changes following
inappropriate vaccine storage. All three final products, ACWY-CRM197, -DT and -TT
conjugate vaccines had expected quality indicator values and similar
immunogenicity in a mouse model (anti-PS IgG and rSBA) when stored at +2-8
degrees C. When stored at >=+37 degrees C, all conjugated carrier proteins and
serogroup saccharides were affected. Direct correlations were observed between
the depolymerization of the MenA saccharide as evidenced by a size-reduction in
the MenA conjugates (CRM197, DT and TT) and their immunogenicity. MenA was the
most labile serogroup, followed by MenC; then MenW and Y, which were similar. At
high temperatures, the conjugated carrier proteins were prone to unfolding and/or
aggregation. The anti-MenC IgG responses of the multivalent conjugate vaccines in
mice were equivalent to those observed in monovalent MenC conjugate vaccines, and
were independent of the carrier protein. For any newly developing MenACWY
saccharide-protein conjugate vaccines, a key recommendation would be to consider
the lyophilization of final product to prevent deleterious degradation that would
affect immunogenicity.
PMID- 28408123
TI - RNA-Binding Proteins in Female Reproductive Pathologies.
AB - RNA-binding proteins are key regulatory molecules involved primarily in post
transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is
critical for adequate cellular growth and survival. Recent reports have shown key
interactions between these RNA-binding proteins and other regulatory elements,
such as miRNAs and long noncoding RNAs, either enhancing or diminishing their
response to RNA stabilization. Many RNA-binding proteins have been reported to
play a functional role in mediation of cytokines involved in inflammation and
immune dysfunction, and some have been classified as global post-transcriptional
regulators of inflammation. The ubiquitous expression of RNA-binding proteins in
a wide variety of cell types and their unique mechanisms of degradative action
provide evidence that they are involved in reproductive tract pathologies.
Aberrant inflammation and immune dysfunction are major contributors to the
pathogenesis and disease pathophysiology of many reproductive pathologies,
including ovarian and endometrial cancers in the female reproductive tract.
Herein, we discuss various RNA-binding proteins and their unique contributions to
female reproductive pathologies with a focus on those mediated by aberrant
inflammation and immune dysfunction.
PMID- 28408125
TI - Influence of Lateral-Medial Sinus Width on No-Grafting Inlay Osteotome Sinus
Augmentation Outcomes.
AB - PURPOSE: Intrasinus new bone formation (BF) has been observed after no-grafting
osteotome sinus augmentation, and it is hypothesized to be influenced by the
dimensions of the maxillary sinus. The aim of this clinical trial is to evaluate
the influence of lateral-medial sinus width (SW) on no-grafting osteotome sinus
augmentation outcomes using cone-beam computed tomography. PATIENTS AND METHODS:
All patients recruited for this prospective study were treated with no-grafting
osteotome sinus augmentation with simultaneous implant placement. Cone-beam
computed tomography was obtained before, immediately after, and 6 months after
the surgical procedure to use for measurements. Descriptive statistics were
calculated and univariate, bivariate, and multivariate analysis were conducted to
evaluate the influence of average SW and other relevant factors on procedure
outcomes, including new BF, residual bone resorption (BR), and change of peri
implant bone height (CPBH). RESULTS: A total of 48 implants placed in 32 elevated
sinuses of 29 patients were included. The average SW was 11.3 +/- 1.8 mm.
Intrasinus BF measured 1.7 +/- 0.9 mm at 6 months after surgery. The amount of BR
was 0.3 +/- 0.9 mm, and CPBH was calculated as 1.3 +/- 1.3 mm. Multivariate
analysis showed a negative correlation between SW and BF (r = -0.469, P = .001),
as well as between SW and CPBH (r = -0.562, P = .001). A positive correlation was
discovered between SW and BR (r = 0.311, P = .027) in general. CONCLUSIONS: The
lateral-medial SW was observed to have a negative correlation with new BF and
CPBH after no-grafting osteotome sinus augmentation.
PMID- 28408124
TI - Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and
Interneuron Propagation of Tau in Vitro.
AB - The clinical progression of Alzheimer disease (AD) is associated with the
accumulation of tau neurofibrillary tangles, which may spread throughout the
cortex by interneuronal tau transfer. If so, targeting extracellular tau species
may slow the spreading of tau pathology and possibly cognitive decline. To
identify suitable target epitopes, we tested the effects of a panel of tau
antibodies on neuronal uptake and aggregation in vitro. Immunodepletion was
performed on brain extract from tau-transgenic mice and postmortem AD brain and
added to a sensitive fluorescence resonance energy transfer-based tau uptake
assay to assess blocking efficacy. The antibodies reduced tau uptake in an
epitope-dependent manner: N-terminal (Tau13) and middomain (6C5 and HT7)
antibodies successfully prevented uptake of tau species, whereas the distal C
terminal-specific antibody (Tau46) had little effect. Phosphorylation-dependent
(40E8 and p396) and C-terminal half (4E4) tau antibodies also reduced tau uptake
despite removing less total tau by immunodepletion, suggesting specific
interactions with species involved in uptake. Among the seven antibodies
evaluated, 6C5 most efficiently blocked uptake and subsequent aggregation. More
important, 6C5 also blocked neuron-to-neuron spreading of tau in a unique three
chamber microfluidic device. Furthermore, 6C5 slowed down the progression of tau
aggregation even after uptake had begun. Our results imply that not all
antibodies/epitopes are equally robust in terms of blocking tau uptake of human
AD-derived tau species.
PMID- 28408127
TI - Double Ileoileal Intussusception Following Surgical Reduction of Ileocolic
Intussusception in an 8-Month-Old Female.
PMID- 28408126
TI - High Risk of Coronary Artery Aneurysms in Infants Younger than 6 Months of Age
with Kawasaki Disease.
AB - OBJECTIVES: To characterize the clinical presentation and outcome in infants <6
months of age with Kawasaki disease (KD) and to describe the use of newer anti
inflammatory therapies in this young population. STUDY DESIGN: We evaluated 88
infants?<6 months old and 632??6 months old treated for KD. We compared
differences in laboratory data, response to treatment, and coronary artery
outcomes between the 2 cohorts. Fisher exact test was used to analyze categorical
variables, whereas the Wilcoxon rank sum test was used for continuous variables.
RESULTS: The majority of children in both cohorts were diagnosed and treated
within the first 10 days of illness (median illness day 6 in both cohorts). For
patients treated within the first 10 days after fever onset, a larger proportion
of infants <6 months old had a dilated or aneurysmal coronary artery on the
initial echocardiogram compared with those ?6 months old (43.4% vs 19.5%).
Furthermore, 18.6% of infants?<6 months old who had a normal echocardiogram at
diagnosis, developed a dilated or aneurysmal coronary artery on a subsequent
echocardiogram within 8 weeks of diagnosis. Twenty-eight infants?<6 months old
received a single dose of infliximab without any untoward effects. CONCLUSIONS:
Despite treatment in the first 10 days, infants?<6 months old with acute KD are
more likely to develop coronary artery abnormalities. Thus, the development of
adjunctive therapies to reduce coronary artery damage should target this
population.
PMID- 28408128
TI - Health Disparities in the Appropriate Management of Cryptorchidism.
AB - OBJECTIVE: To assess regional practices in management of cryptorchidism with
regard to timely fixation by the current recommended age of 18 months. STUDY
DESIGN: A retrospective study was performed. Charts of all patients who underwent
surgical correction for cryptorchidism by a pediatric general surgeon or
urologist within a tertiary pediatric hospital in an urban setting were
systematically reviewed. RESULTS: We identified 1209 patients with
cryptorchidism. The median age of surgical correction was 3.7 years (IQR: 1.4,
7.7); only 27% of patients had surgical correction before 18 months of age. Forty
six percent of our patients were white, 40% were African American, and 8% were
Hispanic. African American and Hispanic patients were less likely to undergo
timely repair (P?=?.01), as were those with public or no insurance (P?=7). No complications were related to the procedure, and 6 patients (11%)
required revision procedures (4 for labral retear, 1 for painful iliopsoas
internal snapping, and 1 for removal of a symptomatic loose body). CONCLUSIONS:
Arthroscopic intervention that encompasses minimal rim resection, restoration of
labral function, and capsular plication significantly improves outcomes in
patients with borderline dysplasia who do not warrant a periacetabular osteotomy.
LEVEL OF EVIDENCE: Level IV, therapeutic case series.
PMID- 28408156
TI - Quadriceps muscle strength reference value as index for functional deterioration
of locomotive organs: Data from 3617 men and women in Japan.
AB - BACKGROUND: Quadriceps muscle strength reference value of normal individuals in
Japan is necessary to quantitatively evaluate functional deterioration of
locomotive organs. Therefore, we established a reference value by using the
Locomo Scan, a new device that measures knee extension muscle strength. METHODS:
We measured knee extension muscle strength with the Locomo Scan in 3617
individuals (1692 men, 1925 women, 20-89 years; mean age. 50.7 years) by
implementing our own 49 measurement events in 20 prefectures. RESULTS: The means
of maximum knee extension muscle strength for men (women) in each age group were
as follows: 20s, 546 (475) N; 30s. 552 (475) N; 40s, 534 (450) N; 50s, 507 (442)
N; 60s, 471 (405) N; 70s, 385 (340) N; and 80s, 359 (267) N. No significant
differences were found from the 20s to 40s age groups, but older groups had
significantly decreased knee extension muscle strength with age for both sexes.
CONCLUSIONS: We established reference values for quadriceps muscle strength with
the Locomo Scan as an index for functional deterioration of locomotive organs
based on a large-scale sample.
PMID- 28408158
TI - Validity of the activPAL3 activity monitor in people moderately affected by
Multiple Sclerosis.
AB - Walking is the primary form of physical activity performed by people with
Multiple Sclerosis (MS), therefore it is important to ensure the validity of
tools employed to measure walking activity. The aim of this study was to assess
the criterion validity of the activPAL3 activity monitor during overground
walking in people with MS. Validity of the activPAL3 accelerometer was compared
to video observation in 20 people moderately affected by MS. Participants walked
20-30m twice along a straight quiet corridor at a comfortable speed. Inter-rater
reliability of video observations was excellent (all intraclass correlations
>0.99). The mean difference (activPAL3- mean of raters) was -4.70+/-9.09,
4.55s+/-10.76 and 1.11s+/-1.11 for steps taken, walking duration and upright
duration respectively. These differences represented 8.7%, 10.0% and 1.8% of the
mean for each measure respectively. The activPAL3 tended to underestimate steps
taken and walking duration in those who walked at cadences of <=38 steps/min by
60% and 47%, respectively. The activPAL3 is valid for measuring walking activity
in people moderately affected by MS. It is accurate for upright duration
regardless of cadence. In participants with slow walking cadences, outcomes of
steps taken and walking duration should be interpreted with caution.
PMID- 28408157
TI - Microsoft Kinect can distinguish differences in over-ground gait between older
persons with and without Parkinson's disease.
AB - Gait patterns differ between healthy elders and those with Parkinson's disease
(PD). A simple, low-cost clinical tool that can evaluate kinematic differences
between these populations would be invaluable diagnostically; since gait analysis
in a clinical setting is impractical due to cost and technical expertise. This
study investigated the between group differences between the Kinect and a 3D
movement analysis system (BTS) and reported validity and reliability of the
Kinect v2 sensor for gait analysis. Nineteen subjects participated, eleven
without (C) and eight with PD (PD). Outcome measures included spatiotemporal
parameters and kinematics. Ankle range of motion for C was significantly less
during ankle swing compared to PD (p=0.04) for the Kinect. Both systems showed
significant differences for stride length (BTS (C 1.24+/-0.16, PD=1.01+/-0.17,
p=0.009), Kinect (C=1.24+/-0.17, PD=1.00+/-0.18, p=0.009)), gait velocity (BTS
(C=1.06+/-0.14, PD=0.83+/-0.15, p=0.01), Kinect (C=1.06+/-0.15, PD=0.83+/-0.16,
p=0.01)), and swing velocity (BTS (C=2.50+/-0.27, PD=2.12+/-0.36, p=0.02), Kinect
(C=2.32+/-0.25, PD=1.95+/-0.31, p=0.01)) between groups. Agreement (RangeICC
=0.93-0.99) and consistency (RangeICC =0.94-0.99) were excellent between systems
for stride length, stance duration, swing duration, gait velocity, and swing
velocity. The Kinect v2 can was sensitive enough to detect between group
differences and consistently produced results similar to the BTS system.
PMID- 28408159
TI - Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma.
AB - Acute idiopathic hyperammonemia in an adult patient is a life-threatening
condition often resulting in a rapid progression to irreversible cerebral edema
and death. While ammonia-scavenging therapies lower blood ammonia levels, in
comparison, clearance of waste nitrogen from the brain may be delayed. Therefore,
we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine
levels, the major reservoir of ammonia, in a gastric bypass patient with
hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia
scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in
mental status mirrored brain glutamine levels, as coma persisted for 48h after
plasma ammonia normalized. We hypothesize that the slower clearance for brain
glutamine levels accounts for the delay in improvement following initiation of
treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain
glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic
monitoring purposes in adult patients presenting with idiopathic hyperammonemia.
PMID- 28408160
TI - Physical training promotes similar effects to the blockade of angiotensin
converting enzyme on the cardiac morphology and function in old female rats
subjected to premature ovarian failure.
AB - We investigated the effects of angiotensin-converting enzyme (ACE) inhibition and
aerobic physical training on the heart of old female rats (82-wk-old) submitted
to premature ovarian failure (10-wk.-old). We used different approaches:
morphology and function by echocardiography, reactivity of the coronary bed and
left ventricular contractibility (Langendorff Technique). Female Wistar
ovariectomized (OVX) rats (n=42) were assigned to one of four groups: OVX,
vehicle treated only; OVX-EM, Enalapril Maleate only (EM, 10mg.kg-1.d-1); OVX-T,
aerobic trained only; and OVX-EMT, treated with Enalapril Maleate and aerobic
trained. Both Enalapril Maleate treatment and aerobic training were done in the
last 20weeks of the experimental protocol. When compared to the OVX group, the
OVX-EM group showed lower values of wall thickness and left ventricular (LV)
mass, lower values of coronary bed reactivity and reduced maximum response of LV
contractility to dobutamine, while the OVX-T group showed lower values of LV wall
thickness, increase in end-systolic volume, reduced maximum response of LV
contractility to dobutamine, and left intraventricular pressure due to increased
flow. The combination of treatments (EM and aerobic physical training) did not
promote additional important effects on the parameters evaluated. Our results
suggest similar beneficial effects of physical training and EM treatment on the
morphology and cardiac function in old female rats submitted to premature ovarian
failure. Although the causes of these benefits are still unknown, both treatments
have promoted a decrease in cardiac contractility, and the reduced beta1
adrenergic sensitivity suggests that both treatments may attenuate the
sympathetic effect on the heart.
PMID- 28408161
TI - Novel thyroid hormone analogues, enzyme inhibitors and mimetics, and their
action.
AB - Thyroid hormones (THs) play key roles in modulating the overall metabolism of the
body, protein synthesis, fat metabolism, neuronal and bone growth, and
cardiovascular as well as renal functions. In this review, we discuss on the
thyroid hormone synthesis and activation, thyroid hormone receptors (TRs) and
mechanism of action, applications of thyroid hormone analogues, particularly the
compounds that are selective ligands for TRbeta receptors, or enzyme inhibitors
for the treatment of thyroidal disorders with a specific focus on thyroid
peroxidase and iodothyronine deiodinases. We also discuss on the development of
small-molecule deiodinase mimetics and their mechanism of deiodination, as these
compounds have the potential to regulate the thyroid hormone levels.
PMID- 28408162
TI - Nuclear protein HMGN2 attenuates pyocyanin-induced oxidative stress via Nrf2
signaling and inhibits Pseudomonas aeruginosa internalization in A549 cells.
AB - Pyocyanin (PCN, 1-hydroxy-5-methyl-phenazine) is one of the most essential
virulence factors of Pseudomonas aeruginosa (PA) to cause various cytotoxic
effects in long-term lung infectious diseases, however the early effect of this
bacterial toxin during PA infection and subsequent autonomous immune response in
host cells have not been fully understood yet. Our results display that early
onset of PCN stimulates Pseudomonas aeruginosa PAO1 adhesion and invasion in A549
cells via ROS production. Non-histone nuclear protein HMGN2 is found to be
involved in the regulation of PCN-induced oxidative stress by promoting
intracellular ROS clearance. Mechanistically, HMGN2 facilitates nuclear
translocation of transcription factor Nrf2 upon PCN stimulation and in turn
elevates antioxidant gene expression. We also found that actin cytoskeleton
dynamics is targeted by ROS, which is to be exploited by PAO1 for host cell
internalization. HMGN2 regulates actin skeleton rearrangement in both PCN
dependent and independent manners and specifically attenuates PCN-mediated PAO1
infection via ROS elimination. These results uncover a novel link between nuclear
protein HMGN2 and Nrf2-mediated cellular redox circumstance and suggest roles of
HMGN2 in autonomous immune response to PA infection.
PMID- 28408163
TI - Angioleiomyoma in the posterior knee: A case report and literature review.
AB - The authors present a case of angioleiomyoma situated in the posterior knee. A 47
year-old Caucasian woman presented in 2011 with recurrent stabbing pain on the
lateral aspect of her right knee. She reported having pain for the last 6years.
She had no history of trauma. In 2008 she was treated with a diagnostic
arthroscopy and transposition of the tibial tuberosity, with no benefit to her
symptoms. Electromyography of the lower limbs showed asymmetry of the amplitude
of sensitive action potential of the superficial fibular nerve. Based on the
clinical suspicion of entrapment of the common fibular nerve at its bifurcation,
a surgical exploration was performed, but pain persisted. In 2014,
ultrasonography localized at the trigger point showed a solid ovular formation of
1cm in diameter situated on the posterior aspect of the external femoral condyle
in proximity to the joint capsule, which was confirmed by magnetic resonance
imaging (MRI). Surgical excision of the 1-cm diameter tumor mass relieved the
symptoms immediately and permanently. Histology evidenced the presence of a solid
type angioleiomyoma. The presence of an angioleiomyoma at the knee joint is very
rare and few cases are reported in the literature. To the authors' knowledge this
is the first time an angioleiomyoma in the posterior knee has been described. In
case of unexplained and persistent pain in and around the knee, clinicians should
be aware of the atypical locations of this tumor, considering that its surgical
excision alone may relieve symptoms permanently.
PMID- 28408165
TI - Alterations in protein phosphorylation in the amygdala of the 5XFamilial
Alzheimer's disease animal model.
AB - Alzheimer's disease is the most common disease underlying dementia in humans. Two
major neuropathological hallmarks of AD are neuritic plaques primarily composed
of amyloid beta peptide and neurofibrillary tangles primarily composed of
hyperphosphorylated tau. In addition to impaired memory function, AD patients
often display neuropsychiatric symptoms and abnormal emotional states such as
confusion, delusion, manic/depressive episodes and altered fear status. Brains
from AD patients show atrophy of the amygdala which is involved in fear
expression and emotional processing as well as hippocampal atrophy. However,
which molecular changes are responsible for the altered emotional states observed
in AD remains to be elucidated. Here, we observed that the fear response as
assessed by evaluating fear memory via a cued fear conditioning test was impaired
in 5XFamilial AD (5XFAD) mice, an animal model of AD. Compared to wild-type mice,
5XFAD mice showed changes in the phosphorylation of twelve proteins in the
amygdala. Thus, our study provides twelve potential protein targets in the
amygdala that may be responsible for the impairment in fear memory in AD.
PMID- 28408164
TI - Comparison of anterior cruciate ligament volume after anatomic double-bundle
anterior cruciate ligament reconstruction.
AB - BACKGROUD: To determine whether anatomic double-bundle anterior cruciate ligament
reconstruction (DB-ACLR) can restore the native ACL volume, and whether the
volume change after reconstruction affects clinical outcomes and re-rupture rates
following the contemporary techniques. METHODS: Eighty patients undergoing
anatomic DB-ACLR using transportal or outside-in technique were prospectively
evaluated with magnetic resonance imaging (MRI) before and after surgery. The ACL
volumes were determined from 3-D models constructed by applying reverse
engineering software. In all participants, measured reconstructed ACL volume were
compared with the ACL on the opposite uninjured side. Participants were divided
into two groups according to the volume of reconstructed graft; larger volume
than native ACL of contra-lateral side (Group 1) or smaller (Group 2). RESULTS:
The mean ACL volume on the reconstructed side (1726.5mm3, 982.1 - 2733.8) was
significantly smaller than that on the uninjured opposite side (1857.6mm3, 958.2
2871.5) (P<0.001). A total of 31 patients in Group 1 and 49 in Group 2 showed no
significant difference of improvement in the clinical outcome scales at the
postoperative two-year follow-up (Lysholm knee score, P=0.830, Tegner activity
score, P=0.848). Four patients with ACL re-rupture during the two-year follow-up
after reconstruction had smaller reconstructed ACL volumes than native ligament
on the opposite site. CONCLUSION: Anatomic DB-ACLR technique restored the graft
volume rather smaller than the volume of the native ACL. Based on the volumetric
consideration, graft reconstructed by anatomic DB-ACLR might have increased
probability of re-rupture due to its smaller volume related to native ACL on the
contralateral side.
PMID- 28408166
TI - Age- and stage-dependent variations of muscle-specific gene expression in brown
trout Salmo trutta L.
AB - This study was conducted to characterize the features of muscle-specific genes
expression during development of brown trout Salmo trutta inhabiting the river
Krivoy ruchey (Kola Peninsula, Russia). Gene expression levels of myogenic
regulatory factors (MRFs - MyoD1 paralogs (MyoD1a, MyoD1b, MyoD1c), Myf5,
myogenin), myostatin paralogs (MSTN-1a, MSTN-1b, MSTN-2a), fast skeletal myosin
heavy chain (MyHC) were measured in the white muscles of brown trout parr of ages
0+ (under-yearling), 1+ (yearling) and 2+ (two year old) and smolts of age 2+.
Multidirectional changes in MyoD1 and MSTN paralogs expression along with
myogenin, Myf 5 and MyHC expression levels in white muscles in parr of trout with
age were revealed. The expression of MyoD1c, myogenin, MSTN-2a was the highest in
0+ parr and then decreased. MyoD1a/b expression levels didn't differ between age
groups. The simultaneous elevation of MyHC, Myf5, MSTN-1a, and MSTN-1b was found
in trout yearlings. In smolts, expression levels of MSTN paralogs, MyHC, Myf5,
MyoD1a was lower than in parr. But in contrast, the MyoD1c and myogenin mRNA
levels was higher in smolts. The study revealed that there are definite patterns
in simultaneous muscle-specific genes expression in age groups of parr and
smolts. As MyoD and MSTN paralogs expression changed differently in dependence on
age and stage, it was suggested that paralogs of the same gene complementarily
control myogenesis during development.
PMID- 28408168
TI - Assessment of targeted automated messages on herpes zoster immunization numbers
in an independent community pharmacy.
AB - OBJECTIVES: To evaluate the impact of an automated phone call by a pharmacy owner
on the number of herpes zoster vaccinations given in the independent community
pharmacy setting, compare herpes zoster immunization numbers in the 3 months
during the previous year to the 3 months during the intervention, and assess
patient satisfaction with the automated phone call service. METHODS: This
prospective study took place in an independent community pharmacy. A message was
recorded by the pharmacy owner using a telephone-message program that notified
patients aged 60 and older that the herpes zoster vaccine is recommended for
them. This message was sent out monthly for a total of 3 months. Patients who
received this vaccine in the 3 months following the initial phone call were
surveyed to determine their reason for receiving the vaccine, and to assess
satisfaction with the phone call. The total number of herpes zoster immunizations
given at the pharmacy during the study period was compared to the total given at
the pharmacy during the same period of the previous year. RESULTS: A total of 25
participants received the herpes zoster vaccine at the pharmacy during the study
period, compared to 16 during the control period. Receiving the phone call was
the most commonly cited reason for receiving the vaccine, followed by doctor
recommendation. Of the 18 participants who received the call, 12 stated that they
would be very likely to respond to similar phone calls in the future. CONCLUSION:
These results demonstrate that using a targeted, automated phone call directed at
eligible patients appears to have a positive effect on their willingness to
receive the herpes zoster vaccine and may lead to an increase in vaccination
numbers among eligible patients. Various factors must be considered before
implementation of this service, including cost and added call volume.
PMID- 28408167
TI - Purification, characterization and expression of transferrin from rainbow trout
seminal plasma.
AB - Transferrin (TF) is recognized as a multifunctional protein and has been
implicated in antioxidative, antimicrobial protection, growth, differentiation
and cytoprotection effects. An efficient, original three-step isolation procedure
for TF consisting in hydrophobic interaction chromatography, gel filtration and
preparative electrophoresis was developed. Rainbow trout TF was found to be N
glycosylated (not O-glycosylated) and phosphorylated at all serine, threonine,
and tyrosine residues. The protein consists of several proteoforms with an
average molecular weight of 76.9kDa and isoelectric point ranging from 5.2 to
5.7. Rainbow trout TF has two functional iron-binding sites and appears to be
quite distinct from carp TF regarding glycosylation and iron-binding properties.
The highest gene expression of TF was detected in liver and testis, the lowest
was detected in head kidney, spleen and efferent ducts. For the first time TF was
identified in the semen of several salmonid species. TF was localized within
testis, mainly in spermatozoa, Sertoli, Leydig cells, as well as in both columnar
secretory and basal cells within the efferent duct. This work contributes to the
existing knowledge information indicating significant variations in TF structure
within teleost fish. The results obtained in this study provide valuable data on
the TF from trout seminal plasma and the physiological role of this protein in
the reproductive tract of salmonids. The results are important for our
understanding of the role of TF in the antioxidant protection and resistance to
pathogenic infections of reproductive cells. The protective role of TF against
environmental pollution with heavy metals, especially during prolonged storage of
spermatozoa in the spermatic duct, as well as regulation of spermatogenesis and
providing Fe for developing germ cells is also postulated.
PMID- 28408169
TI - Prescriber acceptance rate of pharmacists' recommendations.
AB - OBJECTIVES: To determine the prescriber acceptance rates of pharmacists'
recommendations, specifically related to 2 Medicare Part D Star ratings:
appropriate use of high-risk medications (HRMs) in elderly patients and use of
statins for primary prevention in patients with diabetes. The secondary objective
was to assess factors associated with prescriber acceptance. DESIGN:
Retrospective cohort. SETTING AND PARTICIPANTS: Medicare Part D beneficiaries at
a regional grocery store chain pharmacy in Michigan from January 2014 to October
2015. MAIN OUTCOME MEASURES: Prescriber acceptance rate of recommendations
related to HRM use or treatment with a statin in patients with diabetes. RESULTS:
Data were collected and analyzed for 200 patients, of which 100 were recommended
to discontinue an HRM (HRM group) and 100 were recommended statin therapy owing
to diabetes (statin group). Out of the 200 pharmacist-initiated recommendations,
100 were directed to a prescriber and therefore included in the calculation of
prescriber acceptance. Overall, 35.0% of those recommendations were accepted,
with individual group rates of 58.9% (23/39) and 19.7% (12/61) in the HRM group
and statin group, respectively. Patients who were prescribed a statin for primary
prevention of cardiovascular events were more likely to have concurrent
dyslipidemia. CONCLUSION: The prescriber acceptance rates observed in this study
were similar to those reported in published literature. The results of this study
might suggest that prescribers and patients with diabetes may be reluctant to
initiate statin therapy for primary prevention without a concurrent diagnosis of
dyslipidemia. Although further research is required, strategies to optimize
communication and augment patient education may be useful to increase prescriber
as well as patient acceptance of recommendations made by community pharmacists.
PMID- 28408170
TI - Community pharmacists' attitudes toward providing care and services to patients
with severe and persistent mental illness.
AB - OBJECTIVES: To assess community pharmacists' attitudes toward working with
patients who have severe and persistent mental illness (SPMI) and to identify
perceived barriers to providing care and services to this population. DESIGN:
This study was a cross-sectional survey of community pharmacists in North
Carolina. The questionnaire, which was distributed electronically, included
demographic questions about the responder and pharmacy in which they practiced,
Likert-type scale questions assessing pharmacists' comfort and attitudes towards
working with patients with SPMI, and barriers preventing provision of care. The
survey remained open for 30 days after distribution. Descriptive and inferential
statistics were used to analyze survey results. SETTING AND PARTICIPANTS: All
community pharmacists actively licensed in North Carolina. MAIN OUTCOME MEASURES:
Pharmacists' perceptions toward working with and delivering care to patients with
SPMI. RESULTS: Of the 5582 pharmacists who received the survey, 458 completed it.
Most respondents had been practicing 0-5 years (22%) or more than 20 years (51%)
and the majority estimated that 0%- 25% of their patient population had SPMI.
Ninety-one percent agreed that SPMI were real diseases, 81.6% agreed that
patients with SPMI often misunderstand information about their medications, and
53.5% disagreed that patients with SPMI can independently manage their
medications. Pharmacists responded that they felt confident monitoring efficacy
and recognizing adverse effects of medications used to treat SPMI only 28.1% and
48.3% of the time, respectively. The key barriers identified in preventing
community pharmacists from providing optimal care and services to this population
are lack of time and lack of confidence in managing and monitoring medications
used to treat SPMI. CONCLUSION: Although pharmacists had a positive attitude
toward working with this population, multiple barriers were identified that
prevented optimal care. Identifying solutions to overcome these barriers could
help to improve the overall care and increase the likelihood of success in
treating patients with SPMI.
PMID- 28408171
TI - Evaluation of the impact of a residency in an independent pharmacy in rural
Mississippi.
AB - OBJECTIVES: To evaluate the impact of a postgraduate year 1 (PGY1) community
pharmacy residency program on clinical pharmacy service implementation and
enhancement in a rural Mississippi community. SETTING: An independent rural
community pharmacy in Canton, MS. PRACTICE DESCRIPTION AND INNOVATION: Delivery
of clinical pharmacy services provided by PGY1 community residents 1 day a week
to an underserved population during an 18-month period. EVALUATION: Economic
impact of a community pharmacy residency on the pharmacy's revenue stream
determined by calculating an estimated dollar amount generated by clinical
pharmacy services. RESULTS: By providing services 1 day a week, the residents
were able to directly contribute an estimated $8000 of revenue from vaccinations
and medication therapy management services. In addition, residents provided point
of-care testing, facilitated group education, developed a medication
synchronization program, and assisted with physician outreach. CONCLUSION:
Overall, community pharmacy residencies can contribute to the generation of
revenue in rural independent settings and may also offer an opportunity to
generate revenue in different areas that were not present before residency
implementation, thereby improving access to care for patients.
PMID- 28408172
TI - Opioid dispensing and overlap in veterans with non-cancer pain eligible for
Medicare Part D.
AB - OBJECTIVES: Pain is the most prevalent problem among veterans, who receive pain
diagnoses 5 times more frequently than the general population. Opioids are
commonly prescribed for pain, but they have potential for misuse and serious
adverse events. The study objective was to evaluate opioid dispensing patterns
and predictors for overlap in veterans who are eligible for Medicare Part D
benefits. METHODS: A sample of male and all female veterans aged 66 years and
older without cancer in 2005-2009 was included. Overlapping days' supply of
opioids were evaluated within the U.S. Department of Veterans Affairs (VA),
within Part D, and in cross-system users of VA and Part D-reimbursed pharmacies
during 2007-2009. Dispensing patterns were analyzed with t tests and chi-square
tests. Predictors of overlap were identified with general estimating equations.
RESULTS: At least 1 opioid was dispensed to 88.5% of the sample. In 2006 after
Part D implementation, 55.2% of opioids were dispensed by VA, decreasing to 44.3%
in 2009 (P <0.0001). Opioids dispensed from Part D-reimbursed pharmacies had a
higher frequency of overlap compared to those filled at a VA facility (P
<0.0001). While overlapping days' supply for opioids filled at VA decreased,
overlap increased for prescriptions filled at Part D-reimbursed pharmacies (P
<0.0001). There was minimal overlap in opioids between systems, but cross-system
use increased over the study period. Predictors for overlap include females, Part
D enrollment, no VA medication copay, sleep disorders, psychiatric diagnoses, and
substance or alcohol abuse (all P <0.01). Veterans who were Hispanic, older, and
had higher incomes had lower overlap odds (all P <0.0001). CONCLUSIONS: Opioids
dispensed from Part D-reimbursed pharmacies had a higher frequency of overlapping
days' supply as compared to those filled by the VA, but there was minimal overlap
between systems. While overlapping opioid prescriptions filled by the VA
decreased from 2007 to 2009, overlap increased for prescriptions filled at Part D
reimbursed pharmacies. Tools, such as drug monitoring programs, should be used by
VA and non-VA providers to decrease opioid-related harms and misuse.
PMID- 28408173
TI - Re: Risk of Erectile Dysfunction Associated with Use of 5alpha-Reductase
Inhibitors for Benign Prostatic Hyperplasia or Alopecia: Population Based Studies
Using the Clinical Practice Research Datalink.
PMID- 28408174
TI - Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.
AB - BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop
disease recurrence following radical prostatectomy. OBJECTIVE: To identify a
molecular subgroup of prostate cancers with metastatic potential at presentation
resulting in a high risk of recurrence following radical prostatectomy. DESIGN,
SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed
using gene expression data from 70 primary resections, 31 metastatic lymph nodes,
and 25 normal prostate samples. Independent assay validation was performed using
322 radical prostatectomy samples from four sites with a mean follow-up of 50.3
months. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were
identified using unsupervised hierarchical clustering. A partial least squares
approach was used to generate a gene expression assay. Relationships with outcome
(time to biochemical and metastatic recurrence) were analysed using multivariable
Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: A molecular
subgroup of primary prostate cancer with biology similar to metastatic disease
was identified. A 70-transcript signature (metastatic assay) was developed and
independently validated in the radical prostatectomy samples. Metastatic assay
positive patients had increased risk of biochemical recurrence (multivariable
hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence
(multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of
the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an
increased risk of biochemical and metastatic recurrence superior to either model
alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001,
respectively). The retrospective nature of the study is acknowledged as a
potential limitation. CONCLUSIONS: The metastatic assay may identify a molecular
subgroup of primary prostate cancers with metastatic potential. PATIENT SUMMARY:
The metastatic assay may improve the ability to detect patients at risk of
metastatic recurrence following radical prostatectomy. The impact of adjuvant
therapies should be assessed in this higher-risk population.
PMID- 28408176
TI - Using the NSQIP Pancreatic Demonstration Project to Derive a Modified Fistula
Risk Score for Preoperative Risk Stratification in Patients Undergoing
Pancreaticoduodenectomy.
AB - BACKGROUND: The Fistula Risk Score (FRS) is a clinical tool developed from single
institutional data using primarily intraoperative factors to characterize the
risk of clinically relevant pancreatic fistula (CR-POPF) after
pancreaticoduodenectomy. We developed a modified FRS based on objective,
nationally accrued data that is more readily determined before resection. STUDY
DESIGN: The 2012 NSQIP Pancreatic Demonstration Project (PDP) was used to
identify 1,731 pancreaticoduodenectomy resections over 14 months (2011 to 2012).
A randomly generated 70% cohort was used for model development, and the remaining
30% for internal validation. Univariate analysis was used to identify predictors
of CR-POPF. Variables with a value of p < 0.1 were included in multivariable
modeling. RESULTS: Five significant predictors of CR-POPF were identified and
assigned points based on odds ratios: sex, BMI, preoperative total bilirubin,
pancreatic ductal diameter, and gland texture. The 10-point model was further
applied to the 2014 PDP for external validation. In the testing group, risk
scores of 0 to 2 (negligible risk), 3 to 6 (low risk), 7 to 8 (intermediate
risk), and 9 to 10 (high risk) were associated with CR-POPF rates of 0%, 6.7%,
16.4%, and 33.7%, respectively. Similar values were seen using the internal
validation cohort: 0%, 6.3%, 13.5%, and 31.0%, respectively. The external
validation values were 2.9%, 10.2%, 16.4%, and 25.8%, respectively. CONCLUSIONS:
This modified FRS allows for estimation of CR-POPF risk using preoperative and
easily determined intraoperative factors, and will allow comparison of
performance data for individual surgeons to national norms, improved
perioperative counseling, and potential for scrutinizing and/or implementing
interventions designed to decrease CR-POPF rates.
PMID- 28408177
TI - Effectiveness of natriuretic peptide-guided treatment of chronic heart failure. A
meta-analysis.
AB - OBJECTIVE: To evaluate the efficacy of natriuretic peptide (NP)-guided therapy
compared to clinically-guided therapy in reducing mortality and hospital
admissions in chronic heart failure (HF) patients. METHODS: Randomised clinical
trials (RCT) were selected through a systematic review. Four meta-analyses were
conducted for the outcomes of overall mortality, HF-related mortality, overall
hospital admissions, and HF-related hospital admissions. Heterogeneity between
studies and publication bias were also assessed. RESULTS: Nine RCTs were found
with a total of 1914 patients. NP-guided therapy significantly reduced overall
mortality and HF-related hospital admissions. No significant results were found
for HF-related mortality and overall hospital admissions. Some clinical
heterogeneity regarding interventions performed was found between studies.
Publication bias was found for HF-related and overall hospital admissions.
CONCLUSIONS: NP-guided therapy seems to improve outcomes compared to clinically
guided therapy. However, heterogeneity found between interventions might reduce
the generalisation of these results. Specific interventions of the clinical
trials should be examined when making recommendations regarding NP-guided
therapy.
PMID- 28408175
TI - An Oncofetal Glycosaminoglycan Modification Provides Therapeutic Access to
Cisplatin-resistant Bladder Cancer.
AB - BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves
survival of unselected patients with muscle-invasive bladder cancer (MIBC), only
a minority responds to therapy and chemoresistance remains a major challenge in
this disease setting. OBJECTIVE: To investigate the clinical significance of
oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin
resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN,
SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived
from the malaria parasite Plasmodium falciparum (rVAR2) was used as an in situ,
in vitro, and in vivo ofCS-targeting reagent in cisplatin-resistant MIBC. The
ofCS expression landscape was analyzed in two independent cohorts of matched pre-
and post-NAC-treated MIBC patients. INTERVENTION: An rVAR2 protein armed with
cytotoxic hemiasterlin compounds (rVAR2 drug conjugate [VDC] 886) was evaluated
as a novel therapeutic strategy in a xenograft model of cisplatin-resistant MIBC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Antineoplastic effects of
targeting ofCS. RESULTS AND LIMITATIONS: In situ, ofCS was significantly
overexpressed in residual tumors after NAC in two independent patient cohorts
(p<0.02). Global gene-expression profiling and biochemical analysis of primary
tumors and cell lines revealed syndican-1 and chondroitin sulfate proteoglycan 4
as ofCS-modified proteoglycans in MIBC. In vitro, ofCS was expressed on all MIBC
cell lines tested, and VDC886 eliminated these cells in the low-nanomolar IC50
concentration range. In vivo, VDC886 effectively retarded growth of
chemoresistant orthotopic bladder cancer xenografts and prolonged survival
(p=0.005). The use of cisplatin only for the generation of chemoresistant
xenografts are limitations of our animal model design. CONCLUSIONS: Targeting
ofCS provides a promising second-line treatment strategy in cisplatin-resistant
MIBC. PATIENT SUMMARY: Cisplatin-resistant bladder cancer overexpresses
particular sugar chains compared with chemotherapy-naive bladder cancer. Using a
recombinant protein from the malaria parasite Plasmodium falciparum, we can
target these sugar chains, and our results showed a significant antitumor effect
in cisplatin-resistant bladder cancer. This novel treatment paradigm provides
therapeutic access to bladder cancers not responding to cisplatin.
PMID- 28408178
TI - New Insights Into Brain Mechanisms Underlying Neuropsychiatric Symptoms in
Alzheimer Disease.
PMID- 28408179
TI - 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1
Antitrypsin Deficiency.
AB - Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due
principally to the unopposed effects of neutrophil elastase. We previously
reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%
3.8% of the purported therapeutic level at 1 year after a single intramuscular
administration of recombinant adeno-associated virus serotype 1 alpha-1
antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood
and muscle for alpha-1 antitrypsin expression and immune cell response. We also
assayed previously reported markers of neutrophil function known to be altered in
alpha-1 antitrypsin deficient patients. Here, we report sustained expression at
2.0%-2.5% of the target level from years 1-5 in these same patients without any
additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin
vector administration. In addition, we observed partial correction of disease
associated neutrophil defects, including neutrophil elastase inhibition, markers
of degranulation, and membrane-bound anti-neutrophil antibodies. There was also
evidence of an active T regulatory cell response (similar to the 1 year data) and
an exhausted cytotoxic T cell response to adeno-associated virus serotype-1
capsid. These findings suggest that muscle-based alpha-1 antitrypsin gene
replacement is tolerogenic and that stable levels of M-AAT may exert beneficial
neutrophil effects at lower concentrations than previously anticipated.
PMID- 28408182
TI - A yeast growth assay to characterize plant poly(ADP-ribose) polymerase (PARP)
proteins and inhibitors.
AB - Poly(ADP-ribose) polymerases (PARPs) have been implicated in responses of plants
to DNA damage and numerous stresses, whereby the mechanistic basis of the
interference is often unclear. Therefore, the identification of specific
inhibitors and potential interactors of plant PARPs is desirable. For this
purpose, we established an assay based on heterologous expression of PARP genes
from the model plant Arabidopsis thaliana in yeast. Expression of AtPARPs caused
an inhibition of yeast growth to different extent, which was alleviated by
inhibitors targeted at human PARPs. This assay provides a fast and simple means
to identify target proteins and pharmacological inhibitors of AtPARP1.
PMID- 28408181
TI - Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T
Cell Activity to Induce Tolerance.
AB - Targeted approaches to treat autoimmune diseases would improve upon current
therapies that broadly suppress the immune system and lead to detrimental side
effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide)
nanoparticles conjugated with disease-relevant antigen to treat a model of
multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated
antigen both resulted in more durable immune tolerance. To identify active
tolerance mechanisms, we investigated downstream cellular and molecular events
following nanoparticle internalization by antigen-presenting cells. The initial
cell response to nanoparticles indicated suppression of inflammatory signaling
pathways. Direct and functional measurement of surface MHC-restricted antigen
showed positive correlation with both increasing particle dose from 1 to 100
MUg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of
cells expressing MHC-restricted antigen revealed most significant decreases in
positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of
nanoparticles with higher peptide conjugation, whereas expression of a negative
co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice
immunized against myelin proteolipid protein (PLP139-151) were co-cultured with
antigen-presenting cells administered PLP139-151-conjugated nanoparticles, which
resulted in reduced T cell proliferation, increased T cell apoptosis, and a
stronger anti-inflammatory response. These findings indicate several potential
mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific
tolerance.
PMID- 28408180
TI - Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells
Induces Endothelial Injury and Promotes Atherosclerosis.
AB - The vascular response to pro-atherosclerotic factors is a multifactorial process
involving endothelial cells (ECs), macrophages (MACs), and smooth muscle cells
(SMCs), although the mechanism by which these cell types communicate with each
other in response to environmental cues is yet to be understood. Here, we show
that miR-155, which is significantly expressed and secreted in Kruppel-like
factor 5 (KLF5)-overexpressing vascular smooth muscle cells (VSMCs), is a potent
regulator of endothelium barrier function through regulating endothelial
targeting tight junction protein expression. VSMCs-derived exosomes mediate the
transfer of KLF5-induced miR-155 from SMCs to ECs, which, in turn, destroys tight
junctions and the integrity of endothelial barriers, leading to an increased
endothelial permeability and enhanced atherosclerotic progression. Moreover,
overexpression of miR-155 in ECs inhibits endothelial cell
proliferation/migration and re-endothelialization in vitro and in vivo and thus
increases vascular endothelial permeability. Blockage of the exosome-mediated
transfer of miR-155 between these two cells may serve as a therapeutic target for
atherosclerosis.
PMID- 28408183
TI - Outcomes of Stereotactic Body Radiotherapy for T1-T2N0 Small Cell Carcinoma
According to Addition of Chemotherapy and Prophylactic Cranial Irradiation: A
Multicenter Analysis.
AB - BACKGROUND: Although T1-T2N0 non-small cell lung cancer can be managed with
stereotactic body radiotherapy (SBRT) alone, this management has often been
extrapolated to T1-T2N0 small cell lung cancer (SCLC). This secondary analysis of
a multi-institutional cohort study investigated whether the addition of
chemotherapy and prophylactic cranial irradiation (PCI) improved the outcomes for
these patients. MATERIALS AND METHODS: All cases of histologically confirmed T1
T2N0M0 SCLC were obtained from 24 institutions' prospectively collected SBRT
databases. The clinical and treatment characteristics, toxicities, outcomes, and
patterns of failure were assessed. We used Kaplan-Meier analysis to evaluate the
survival outcomes. Univariate and multivariate analyses identified the predictors
of outcomes. RESULTS: From 24 institutions, 76 lesions were treated in 74
patients (median follow-up, 18 months). Chemotherapy and PCI were delivered in
56% and 23% of cases, respectively. The median SBRT dose per fraction was 50 Gy/5
fractions. Patients receiving chemotherapy experienced increased median disease
free survival (61.3 vs. 9.0 months; P = .02) and overall survival (31.4 vs. 14.3
months; P = .02). Chemotherapy independently predicted for better outcomes for
disease-free survival and overall survival on multivariate analysis (P = .01).
Toxicities were uncommon; 5.2% experienced grade >= 2 pneumonitis. Post-treatment
failures were most commonly distant (45.8% of recurrences), followed by nodal
(25.0%), and elsewhere in the lung (20.8%). The median time to each was 5 to 7
months. CONCLUSION: Patients undergoing primary SBRT for T1-T2N0 SCLC should also
undergo additional chemotherapy. No established role was found for PCI in this
population.
PMID- 28408184
TI - Posterior reversible encephalopathy syndrome (PRES) with obstructive
hydrocephalus.
PMID- 28408185
TI - Microplastic ingestion in fish larvae in the western English Channel.
AB - Microplastics have been documented in marine environments worldwide, where they
pose a potential risk to biota. Environmental interactions between microplastics
and lower trophic organisms are poorly understood. Coastal shelf seas are rich in
productivity but also experience high levels of microplastic pollution. In these
habitats, fish have an important ecological and economic role. In their early
life stages, planktonic fish larvae are vulnerable to pollution, environmental
stress and predation. Here we assess the occurrence of microplastic ingestion in
wild fish larvae. Fish larvae and water samples were taken across three sites
(10, 19 and 35 km from shore) in the western English Channel from April to June
2016. We identified 2.9% of fish larvae (n = 347) had ingested microplastics, of
which 66% were blue fibres; ingested microfibers closely resembled those
identified within water samples. With distance from the coast, larval fish
density increased significantly (P < 0.05), while waterborne microplastic
concentrations (P < 0.01) and incidence of ingestion decreased. This study
provides baseline ecological data illustrating the correlation between waterborne
microplastics and the incidence of ingestion in fish larvae.
PMID- 28408186
TI - Water contamination from oil extraction activities in Northern Peruvian Amazonian
rivers.
AB - Oil extraction activities in the Northern Peruvian Amazon have generated a long
standing socio-environmental conflict between oil companies, governmental
authorities and indigenous communities, partly derived from the discharge of
produced waters containing high amounts of heavy metals and hydrocarbons. To
assess the impact of produced waters discharges we conducted a meta-analysis of
2951 river water and 652 produced water chemical analyses from governmental
institutions and oil companies reports, collected in four Amazonian river basins
(Maranon, Tigre, Corrientes and Pastaza) and their tributaries. Produced water
discharges had much higher concentrations of chloride, barium, cadmium and lead
than are typically found in fresh waters, resulting in the widespread
contamination of the natural water courses. A significant number of water samples
had levels of cadmium, barium, hexavalent chromium and lead that did not meet
Peruvian and international water standards. Our study shows that spillage of
produced water in Peruvian Amazon rivers placed at risk indigenous population and
wildlife during several decades. Furthermore, the impact of such activities in
the headwaters of the Amazon extended well beyond the boundaries of oil
concessions and national borders, which should be taken into consideration when
evaluating large scale anthropogenic impacts in the Amazon.
PMID- 28408187
TI - Microplastics in sediments of the Changjiang Estuary, China.
AB - Microplastics are plastics that measure less than 5 mm in diameter. They enter
the marine environment as primary sources directly from industrial uses, as well
as secondary sources resulting from the degradation of large plastic debris. To
improve the knowledge of microplastic pollution in China, we investigated samples
from 53 estuarine sediment locations collected with a box corer within the
Changjiang Estuary. Microplastics (<5 mm) were extracted from sediments by
density separation, after which they were observed under a microscope and
categorized according to shape, color and size. Identification was carried out
using Micro-Fourier-Transform Infrared Spectroscopy (MU-FT-IR). The abundance of
microplastics in the Changjiang Estuary was mapped. The mean concentration was
121 +/- 9 items per kg of dry weight, varying from 20 to 340 items per kg of dry
weight. It was found that the concentration of microplastics was the highest on
the southeast coast of Shanghai. The distribution pattern of microplastics may be
affected by the Changjiang diluted water in summer. All of the microplastics
collected were categorized according to shape, color and size. Among which fiber
(93%), transparent (42%) and small microplastics (<1 mm) (58%) were the most
abundant types. No clear correlation between microplastics and the finer sediment
fraction was found. Rayon, polyester, and acrylic were the most abundant types of
microplastics identified, indicating that the main source of microplastics in the
Changjiang Estuary was from washing clothes (the primary source). It is possible
to compare microplastic abundance in this study with the results of other related
studies using the same quantification method. The identification of microplastics
raises the awareness of microplastic pollution from drainage systems. The
prevalence of microplastic pollution calls for monitoring microplastics at a
national scale on a regular basis.
PMID- 28408188
TI - Investigation and risk evaluation of the occurrence of carbamazepine,
oxcarbazepine, their human metabolites and transformation products in the urban
water cycle.
AB - Trace organic contaminants such as pharmaceuticals, personal care products and
industrial chemicals are frequently detected in the urban water cycle, including
wastewater, surface water and groundwater, as well as drinking water. These also
include human metabolites (HMs), which are formed in the human body and then
excreted via urine or feces, as well as transformation products (TPs) formed in
engineered treatment systems and the aquatic environment. In the current study,
the occurrence of HMs as well as their TPs of the anticonvulsants carbamazepine
(CBZ) and oxcarbazepine (OXC) were investigated using LC tandem MS in effluents
of wastewater treatment plants (WWTPs), surface water and groundwater. Highest
concentrations were observed in raw wastewater for 10,11-dihydro-10,11
dihydroxycarbamazepine (DiOHCBZ), 10,11-dihydro-10-hydroxy-cabamazepine (10OHCBZ)
and CBZ with concentrations ranging up to 2.7 +/- 0.4, 1.7 +/- 0.2 and 1.07 +/-
0.06 MUg L-1, respectively. Predictions of different toxicity endpoints using a
Distributed Structure-Searchable Toxicity (DSSTox) expert system query indicated
that several HMs and TPs, in particular 9-carboxy-acridine (9-CA-ADIN) and
acridone (ADON), may exhibit an increased genotoxicity compared to the parent
compound CBZ. As 9-CA-ADIN was also detected in groundwater, a detailed
investigation of the genotoxicity of 9-CA-ADIN is warranted. Investigations of an
advanced wastewater treatment plant further revealed that the discharge of the
investigated compounds into the aquatic environment could be substantially
reduced by ozonation followed by granular activated carbon (GAC) filtration.
PMID- 28408189
TI - Genetic Effects on the Correlation Structure of CVD Risk Factors: Exome-Wide Data
From a Ghanaian Population.
AB - Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly
correlated with several cardiovascular disease (CVD) risk factors. It also plays
a direct role in CVD, including myocardial infarction and stroke, by impeding the
dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to
its endpoints, genetic variants modulating the relationship between PAI-1 and
risk factors may be of particular clinical and biological interest. The high
heritability of PAI-1, which has not been explained by genetic association
studies, may also, in large part, be due to this relationship with CVD risk
factors. Using exome-wide data from 1,032 Ghanaian study participants, we tested
for heterogeneity of correlation by genotype between PAI-1 and 4 CVD risk factors
(body mass index, triglycerides, mean arterial pressure, and fasting glucose)
under the hypothesis that loci involved in the relationship between PAI-1 and
other risk factors will also modify their correlational structure. We found more
significant heterogeneities of correlation by genotype than we found marginal
effects, with no evidence of type I inflation. The most significant result among
all univariate and multivariate tests performed in this study was the
heterogeneity of correlation between PAI-1 and mean arterial pressure at
rs10738554, near SLC24A2, a gene previously associated with high blood pressure
in African Americans.
PMID- 28408191
TI - Cross-cultural validity of the theory of planned behavior for predicting healthy
food choice in secondary school students of Inner Mongolia.
AB - AIMS: Unhealthy eating behavior is a serious health concern among secondary
school students in Inner Mongolia. To predict their healthy food choices and
devise methods of correcting unhealthy choices, we sought to confirm the cross
cultural validity of the theory of planned behavior among Inner Mongolian
students. MATERIALS AND METHODS: A cross-sectional study, conducted between
November and December 2014. Overall, 3047 students were enrolled. We devised a
questionnaire based on the theory of planned behavior to measure its components
(intentions, attitudes, subjective norms, and perceived behavioral control) in
relation to healthy food choices; we also assessed their current engagement in
healthy food choices. RESULTS: A principal component analysis revealed high
contribution rates for the components (69.32%-88.77%). A confirmatory factor
analysis indicated that the components of the questionnaire had adequate model
fit (goodness of fit index=0.997, adjusted goodness of fit index=0.984,
comparative fit index=0.998, and root mean square error of approximation=0.049).
Notably, data from participants within the suburbs did not support the theory of
planned behavior construction. Several paths did not predict the hypothesis
variables. However, attitudes toward healthy food choices strongly predicted
behavioral intention (path coefficients 0.49-0.77, p<0.01), regardless of
demographic characteristics. CONCLUSION: Our results support that the theory of
planned behavior can apply to secondary school students in urban areas.
Furthermore, attitudes towards healthy food choices were the best predictor of
behavioral intentions to engage in such choices in Inner Mongolian students.
PMID- 28408190
TI - Identification of selective inhibitors of sphingosine kinases 1 and 2 through a
structure-activity relationship study of 4-epi-jaspine B.
AB - We recently reported that 4-epi-jaspine B exhibits potent inhibitory activity
towards sphingosine kinases (SphKs). In this study, we investigated the effects
of modifying the 2-alkyl group, as well as the functional groups on the THF ring
of 4-epi-jaspine B using a diversity-oriented synthesis approach based on a late
stage cross metathesis reaction. The introduction of a p-phenylene tether to the
alkyl group was favored in most cases, whereas the replacement of a carbon atom
with an oxygen atom led to a decrease in the inhibitory activity. Furthermore,
the introduction of a bulky alkyl group at the terminus led to a slight increase
in the inhibitory activity of this series towards SphKs compared with 4-epi
jaspine B (the Q values of compound 13 for SphK1 and SphK2 were 0.2 and 0.4,
respectively). Based on this study, we identified two isoform selective
inhibitors, including the m-phenylene derivative 4 [IC50 (SphK1) >=30MUM; IC50
(SphK2)=2.2MUM] and the methyl ether derivative 22 [IC50 (SphK1)=4.0MUM; IC50
(SphK2) >=30MUM].
PMID- 28408192
TI - [Kick-off article: Patients first in health care: Status quo].
AB - "Putting patients first in health care" seems to be a rhetorical statement. But
is it really the case that patients always come first? And where exactly do we
stand with patient involvement and patient orientation in Germany? What
participation options are currently available? Is the patient involvement and
patient orientation we have so far achieved sufficient? What needs to be done?
These questions will be addressed in the following discussion. Patient self-help
organizations, patient interest groups, patient representatives as well as the
industrial and political decision-making bodies agree that the patient
perspective should be more strongly integrated into health care and health care
delivery decisions. The relevant information and sources of evidence, however,
are yet insufficiently provided and used. Patients are experts for their own
cause. There is consensus that patient participation is and must be an integral
part of all levels of health care. Patient representation has made enormous
progress in the last decade. This article outlines the current state of affairs
of patient representation, patient involvement, their legal legitimacy and
possible future scenarios. The transformation from of a paternalistically
oriented health care system towards a patient-oriented system is far advanced,
but much remains to be done. (As supplied by guesteditors).
PMID- 28408193
TI - Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a
double-blind, randomised study.
AB - BACKGROUND: Functional somatic syndromes, including chronic fatigue syndrome or
irritable bowel syndrome, often co-exist. Treatment guidelines supported by high
quality evidence exist for most functional somatic syndromes, but are lacking for
multiple comorbid functional somatic syndromes. We aimed to assess the effect of
the tricyclic antidepressant, imipramine, in patients with multiple functional
somatic syndromes defined by the criteria for multiorgan bodily distress
syndrome, a unifying diagnosis that encompasses most functional somatic syndromes
and somatoform disorders. METHODS: In this single-centre, double-blind,
randomised trial done in a Danish university hospital setting, participants were
patients consecutively referred (age 20-50 years) fulfilling criteria for
multiorgan bodily distress syndrome with no concurrent comorbid depression or
anxiety disorder. Participants were randomly assigned (1:1) to receive either 10
weeks of low-dose imipramine or placebo (oral daily doses of 25-75 mg). The
hospital pharmacy handled randomisation (computer-generated) and masking,
providing sequentially numbered packs of study drug that were given serially to
the participants. All others involved were masked to allocation. Primary outcome
was patient-rated overall health improvement on a 5-point clinical global
improvement scale. Improvement was defined as patients responding "better" or
"much better" as opposed to "unchanged" and "worse" or "much worse" when rating
their overall health status after 10 weeks of minimum 25 mg study drug. Analyses
included patients who received at least one dose of study drug. This study is
registered with ClinicalTrials.gov, number NCT01518634. FINDINGS: Between Jan 30,
2012, and Nov 24, 2014, 138 patients were randomly assigned; 70 to receive
imipramine and 68 to receive placebo. The study was completed on May 1, 2015. 125
patients received at least one dose of study drug: 65 received imipramine and 60
received placebo. Treatment was terminated prematurely for eight (12%) patients
receiving imipramine and seven (12%) patients receiving placebo. Data were
missing for two (3%) patients receiving imipramine and three (5%) patients
receiving placebo. Of the 120 patients (96%) who provided primary outcome data,
33 (53%) receiving imipramine reported their overall health status as "better" or
"much better" compared with 14 patients (25%) receiving placebo. The improvement
after imipramine was significantly greater than after placebo (odds ratio 3.3
[95% CI 1.6-6.8]; p=0.001). Number needed to treat was 3.6 (95% CI 2.3-8.9).
Analysis of the worst-case scenario for patients with missing outcome did not
change the interpretation of the results. 32 patients (49%) receiving imipramine
and 10 patients (17%) receiving placebo had at least one adverse event of
moderate intensity (p=0.0001); eight patients (12%) receiving imipramine and
three patients (5%) receiving placebo had at least one adverse event of severe
intensity (p=0.1496). One patient (1%) receiving placebo experienced a serious
adverse event (a subdural haematoma sustained after an accident). Adverse events
caused dropout in four patients (6%) receiving imipramine and three patients (5%)
receiving placebo. INTERPRETATION: Imipramine treatment compared with placebo
significantly improved overall health in patients with multiple functional
somatic syndromes when both treatments were supported by regular contacts with
clinicians. Adverse events were more common in the imipramine group, but only
rarely led to discontinuation of treatment. FUNDING: The Danish Foundation,
Trygfonden.
PMID- 28408195
TI - Editorial Comment.
PMID- 28408194
TI - Low dose imipramine for multiple functional somatic syndromes.
PMID- 28408196
TI - Genotoxicity testing of sodium formononetin-3'-sulphonate (Sul-F) by assessing
bacterial reverse mutation, chromosomal aberrations and micronucleus tests.
AB - As part of a safety evaluation, we evaluated the potential genotoxicity of sodium
formononetin-3'-sulphonate (Sul-F) using bacterial reverse mutation assay,
chromosomal aberrations detection, and mouse micronucleus test. In bacterial
reverse mutation assay using five strains of Salmonella typhimurium (TA97, TA98,
TA100, TA102 and TA1535), Sul-F (250, 500, 1000, 2000, 4000 MUg/plate) did not
increase the number of revertant colonies in any tester strain with or without S9
mix. In a chromosomal assay using Chinese hamster lung fibroblast (CHL) cells,
there were no increases in either kind of aberration at any dose of Sul-F (400,
800, and 1600 MUg/mL) treatment groups with or without S9 metabolic activation.
In an in vivo bone marrow micronucleus test in ICR mice, Sul-F at up to 2000
mg/kg (intravenous injection) showed no significant increases in the incidence of
micronucleated polychromatic erythrocytes, and the proportion of immature
erythrocytes to total erythrocytes. The results demonstrated that Sul-F does not
show mutagenic or genotoxic potential under these test conditions.
PMID- 28408198
TI - Plasma 8-iso-Prostaglandin F2alpha, a possible prognostic marker in aneurysmal
subarachnoid hemorrhage.
AB - BACKGROUND: 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha) is a potential
biomarker of oxidative stress. This study clarified whether plasma 8-iso
PGF2alpha concentrations were affected and its underlying relevance to prognosis
in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective,
observational study, a total of 170 controls and 170 aSAH patients were enrolled.
Plasma 8-iso-PGF2alpha concentrations were detected using an ELISA. Severity was
assessed by World Federation of Neurological Surgeons (WFNS) scale and modified
Fisher grading scale. Clinical outcomes included 6-month mortality and poor
outcome referred to as Glasgow outcome scale score of 1-3. RESULTS: As compared
to controls, admission plasma 8-iso-PGF2alpha concentrations were significantly
enhanced. Increased concentrations of plasma 8-iso-PGF2alpha correlated with WFNS
scores and modified Fisher scores. 8-iso-PGF2alpha in plasma was an independent
predictor for clinical outcomes. Under ROC curve, the predictive values of 8-iso
PGF2alpha concentrations resembled those of WFNS scores and modified Fisher
scores for clinical outcomes. CONCLUSIONS: An elevation in plasma 8-iso-PGF2alpha
concentrations is associated with the severity and poor outcome after aSAH,
substantializing 8-iso-PGF2alpha as a potential prognostic biomarker of aSAH.
PMID- 28408197
TI - A new orthodontic force system for moment control utilizing the flexibility of
common wires: Evaluation of the effect of contractile force and hook length.
AB - BACKGROUND/PURPOSE: The application of an appropriate force system is
indispensable for successful orthodontic treatments. Second-order moment control
is especially important in many clinical situations, so we developed a new force
system composed of a straight orthodontic wire and two crimpable hooks of
different lengths to produce the second-order moment. The objective of this study
was to evaluate this new force system and determine an optimum condition that
could be used in clinics. METHODS: We built a premolar extraction model with two
teeth according to the concept of a modified orthodontic simulator. This system
was activated by applying contractile force from two hooks that generated second
order moment and force. The experimental device incorporated two sensors, and
forces and moments were measured along six axes. We changed the contractile force
and hook length to elucidate their effects. Three types of commercial wires were
tested. RESULTS: The second-order moment was greater on the longer hook side of
the model. Vertical force balanced the difference in moments between the two
teeth. Greater contractile force generated a greater second-order moment, which
reached a limit of 150 g. Excessive contractile force induced more undesired
reactions in the other direction. Longer hooks induced greater moment generation,
reaching their limit at 10 mm in length. CONCLUSION: The system acted similar to
an off-center V-bend and can be applied in clinical practice as an unconventional
loop design. We suggest that this force system has the potential for second-order
moment control in clinical applications.
PMID- 28408199
TI - Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide
hydrogels for combined immuno-chemotherapy.
AB - In situ-forming thermosensitive hydrogels based on poly(ethylene glycol)
poly(gamma-ethyl-l-glutamate) diblock copolymers (mPEG-b-PELG) were prepared for
the co-delivery of interleukin-15 (IL-15) and cisplatin (CDDP). The polypeptide
based hydrogels as local drug delivery carriers could reduce the systemic
toxicity, degrade thoroughly within 3weeks after subcutaneous injection into rats
and display an acceptable biocompatibility. When incubated with mouse melanoma
B16 cells, only the CDDP-treated groups had significant effects on the S phase
cell-cycle arrest in melanoma cells. After a single peritumoral injection of the
hydrogel containing IL-15/CDDP in C57BL/6 mice inoculated with B16F0-RFP melanoma
cells, the dual drug-loaded hydrogels displayed synergistic anticancer efficacy,
which was resulted from a combination of CDDP-mediated S arrest and IL-15/CDDP
induced recovery of CD8+ T cell and NK cell populations to reduce
immunosuppression and enhance antitumor immunity. Hence, the as-prepared
thermosensitive polypeptide hydrogels for localized and sustained co-delivery of
IL-15 and CDDP may have potential for efficient treatment of melanoma.
PMID- 28408200
TI - Angiogenesis-targeting microbubbles combined with ultrasound-mediated gene
therapy in brain tumors.
AB - The major challenges in gene therapy for brain cancer are poor transgene
expression due to the blood-brain barrier (BBB) and neurologic damage caused by
conventional intracerebral injection. Non-viral gene delivery using ultrasound
targeted microbubbles (MBs) oscillation via the systematic transvascular route is
attractive, but there is currently no high-yielding and targeted gene expression
method. In this study, we developed a non-viral and angiogenesis-targeting gene
delivery approach for efficient brain tumor gene therapy without brain damage. We
developed a VEGFR2-targeted and cationic microbubbles (VCMBs) gene vector for use
with transcranial focused ultrasound (FUS) exposure to allow transient gene
delivery. The system was tested in a brain tumor model using the firefly
luciferase gene and herpes simplex virus type 1 thymidine kinase/ganciclovir
(pHSV-TK/GCV) with VCMBs under FUS exposure for transgene expression and anti
tumor effect. In vitro data showed that VCMBs have a high DNA-loading efficiency
and high affinity for cancer cells. In vivo data confirmed that this technique
enhanced gene delivery into tumor tissues without affecting normal brain tissues.
The VCMBs group resulted in higher luciferase expression (3.8 fold) relative to
the CMBs group (1.9 fold), and the direct injection group. The tumor volume on
day 25 was significantly smaller in rats treated with the pHSV-TK/GCV system
using VCMBs under FUS (9.7+/-5.2mm3) than in the direct injection group (40.1+/
4.3mm3). We demonstrated the successful use of DNA-loaded VCMBs and FUS for non
viral, non-invasive and targeted gene delivery to brain tumors.
PMID- 28408201
TI - Spatio-temporal control strategy of drug delivery systems based nano structures.
AB - The drug instability, toxicity and the barrier to the target area necessitate a
suitable drug delivery system with an external or internal control of the
release. Spatio-temporal control using a surface functionalized nano-carrier
seems to be the best alternative for guided drug delivery and release. This
manuscript provides a broad spectrum about the drug carrier interface
modification to cover the need for temporal drug delivery control under neglect
side effects. On the other hand, recent advances related to the drug vehicle are
highlighted, besides physical (Electric field, magnetic field, light) or
mechanical (Ultrasound, mechanical strain), chemical (pH, redox gradient, enzyme)
stimuli mediated DDS. Precisely, the paper focus on the NIR light as an effective
external stimulus for remotely-triggered DDS. NIR responsive drug delivery
systems are considered as novel drug modality that ensures an eco-friendly
spatiotemporal control and an administrated meditation. This study also
investigated the NIIR spectroscopy (NIRS) combined with partial least square
(PLS) for quantitative analysis of a polyvinyl alcohol based prodrug (PVA-DOX) in
order to reveal the high potential of NIRS for drug release monitoring and the
extraction of concise calibration models.
PMID- 28408202
TI - Airway Clearance Techniques for Primary Ciliary Dyskinesia; is the Cystic
Fibrosis literature portable?
AB - Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired
mucociliary clearance. Airway clearance techniques (ACTs) are commonly
recommended for patients with PCD to facilitate mucus clearance, despite a lack
of evidence in this group. Current physiotherapy practice in PCD is based on
evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses
on the available evidence and outlines challenges in extrapolating evidence
between the conditions for best clinical practice.
PMID- 28408203
TI - Surgeon Involvement in Transcatheter Aortic Valve Replacement in the United
States: A 2016 Society of Thoracic Surgeons Survey.
AB - BACKGROUND: The Society of Thoracic Surgeons (STS) surveyed cardiothoracic
surgeon participants in its Adult Cardiac Surgery Database (ACSD) to learn the
extent of surgeon involvement in transcatheter aortic valve replacement (TAVR)
procedures. METHODS: An electronic survey was delivered to 2,594 surgeons in June
2016. When the survey closed 2 weeks later, 487 completed surveys had been
submitted for a response rate of 18.8%. RESULTS: Among the 487 participants in
the ACSD who responded to the survey, 410 (84.2%) reported that TAVR was
performed at their institutions. Approximately three-quarters reported that they
performed TAVR procedures as part of a heart team (77.5%; 313 of 404),
cardiologists and cardiothoracic surgeons were jointly responsible for TAVR
referrals (83.7%; 339 of 405), and TAVR programs were administered either jointly
by the cardiology and cardiac surgery departments or exclusively by the cardiac
surgery department (73.3%; 297 of 405). A majority were involved in the pre-,
intra-, and postoperative care of patients undergoing TAVR, with 91.4% (370 of
405) reporting participation in multidisciplinary meetings, at least 50%
regularly performing technical aspects in 10 of 11 conduct of operation
categories, and 86.6% (266 of 307) caring for patients undergoing TAVR after the
procedure. CONCLUSIONS: Cardiac surgeons in the United States are active
participants in the management of patients with aortic stenosis as part of the
heart team. The STS survey found that not only were they actively involved in the
treatment decision-making process but they also played a significant role in the
valve procedure, including deployment and postprocedural care. The heart team
model continues to evolve and should be expanded into other areas of structural
heart disease.
PMID- 28408204
TI - Distribution and medical aspects of Loxosceles rufescens, one of the most
invasive spiders of the world (Araneae: Sicariidae).
AB - Loxosceles rufescens is a circum-Mediterranean spider species, potentially
harmful to humans. Its native area covers the Mediterranean Basin and Near East.
Easily spread with transported goods, it is meanwhile an alien and invasive
species to nearly all other continents and many islands. This species occurs in
semi-arid steppe-like habitats, typically under stones and in cavities, which
enables it to settle inside buildings when invading the synanthropic environment.
This review analyses the literature of L. rufescens bites to humans (38
publications) of which only 11 publications refer to 12 verified spider bites
(11% of the reported bites). Two published allegedly deadly spider bites
(Thailand 2014 and Italy 2016) involve non-verified spider bites and are thus not
reliable. The symptoms and therapy of these 11 verified bites are described: only
five cases showed moderate systemic effects, nine cases developed necrosis, four
cases needed surgical debridement, all cases healed without complications within
a few weeks. In conclusion, L. rufescens is a spider species globally spread by
human activity, it rarely bites humans and the bites are less harmful than often
described. There is no known fatal issue.
PMID- 28408205
TI - Temporal, spatial, and phenotypical changes of PDGFRalpha expressing fibroblasts
during late lung development.
AB - Many studies have investigated the source and role of epithelial progenitors
during lung development; such information is limited for fibroblast populations
and their complex role in the developing lung. In this study, we characterized
the spatial location, mRNA expression and Immunophenotyping of PDGFRalpha+
fibroblasts during sacculation and alveolarization. Confocal microscopy
identified spatial association of PDGFRalpha expressing fibroblasts with proximal
epithelial cells of the branching bronchioles and the dilating acinar tubules at
E16.5; with distal terminal saccules at E18.5; and with alveolar epithelial cells
at PN7 and PN28. Immunohistochemistry for alpha smooth muscle actin revealed that
PDGFRalpha+ fibroblasts contribute to proximal peribronchiolar smooth muscle at
E16.5 and to transient distal alveolar myofibroblasts at PN7. Time series RNA-Seq
analyses of PDGFRalpha+ fibroblasts identified differentially expressed genes
that, based on gene expression similarity were clustered into 7 major gene
expression profile patterns. The presence of myofibroblast and smooth muscle
precursors at E16.5 and PN7 was reflected by a two-peak gene expression profile
on these days and gene ontology enrichment in muscle contraction. Additional
molecular and functional differences between peribronchiolar smooth muscle cells
at E16.5 and transient intraseptal myofibroblasts at PN7 were suggested by a
single peak in gene expression at PN7 with functional enrichment in cell
projection and muscle cell differentiation. Immunophenotyping of subsets of
PDGFRalpha+ fibroblasts by flow cytometry confirmed the predicted increase in
proliferation at E16.5 and PN7, and identified subsets of CD29+ myofibroblasts
and CD34+ lipofibroblasts. These data can be further mined to develop novel
hypotheses and valuable understanding of the molecular and cellular basis of
alveolarization.
PMID- 28408207
TI - Transactivator protein: An alternative for delivery of recombinant proteins for
safer reprogramming of induced Pluripotent Stem Cell.
AB - Induced pluripotent stem cells (iPSC) are somatic cells reprogrammed to
pluripotency by forced expression of pluripotency factors. These cells are shown
to have the same pluripotent potential as embryonic stem cells (ESC) and
considered as an alternative to the much controversial usage of ESC which
involved human embryos. However, the traditional method in reprogramming cells
into iPSC using genome-integrating retro- or lenti- viruses remains an obstacle
for its application in clinical setting. Although numerous studies have been
conducted for a safer DNA-based reprogramming, reprogramming of iPSC by genetic
modifications may raise the possibility of malignant transformation and has been
a major limitation for its usage in clinical applications. Therefore, there is a
need for an alternative method to reprogram the cells without the use of gene
editing and a much safer way to deliver transcription factors to induce
pluripotency on target cells. Using protein transduction approach, a number of
studies have demonstrated the generation of human iPSCs from human fibroblasts
and mouse embryonic fibroblasts by direct delivery of reprogramming proteins. In
this review, the definition and mechanism of HIV-TAT protein (a type of protein
transduction domain) in delivering recombinant proteins, including the potential
of protein-based delivery to induce iPSC were further discussed.
PMID- 28408206
TI - Towards understanding the molecular basis of ion channel modulation by lipids:
Mechanistic models and current paradigms.
AB - Research on ion channel modulation has become a hot topic because of the key
roles these membrane proteins play in both prokaryotic and eukaryotic organisms.
In this respect, lipid modulation adds to the overall modulatory mechanisms as a
potential via to find new pharmacological targets for drug design based on
interfering with lipid/channel interactions. However, our knowledge in this field
is scarce and often circumscribed to the sites where lipids bind and/or its final
functional consequences. To fully understand this process it is necessary to
improve our knowledge on its molecular basis, from the binding sites to the
signalling pathways that derive in structural and functional effects on the ion
channel. In this review, we have compiled information about such mechanisms and
established a classification into four different modes of action. Afterwards, we
have revised in more detail the lipid modulation of Cys-loop receptors and of the
potassium channel KcsA, which were chosen as model channels modulated by specific
lipids. This article is part of a Special Issue entitled: Membrane Lipid Therapy:
Drugs Targeting Biomembranes edited by Pablo V. Escriba.
PMID- 28408208
TI - Establishing alighting preferences and species transmission differences for Pea
seed-borne mosaic virus aphid vectors.
AB - Pea seed-borne mosaic virus (PSbMV) infection causes a serious disease of field
pea (Pisum sativum) crops worldwide. The PSbMV transmission efficiencies of five
aphid species previously found landing in south-west Australian pea crops in
which PSbMV was spreading were studied. With plants of susceptible pea cv. Kaspa,
the transmission efficiencies of Aphis craccivora, Myzus persicae, Acyrthosiphon
kondoi and Rhopalosiphum padi were 27%, 26%, 6% and 3%, respectively. Lipaphis
erysimi did not transmit PSbMV in these experiments. The transmission
efficiencies found for M. persicae and A. craccivora resembled earlier findings,
but PSbMV vector transmission efficiency data were unavailable for A. kondoi, R.
padi and L. erysimi. With plants of partially PSbMV resistant pea cv. PBA
Twilight, transmission efficiencies of M. persicae, A. craccivora and R. padi
were 16%, 12% and 1%, respectively, reflecting putative partial resistance to
aphid inoculation. To examine aphid alighting preferences over time, free-choice
assays were conducted with two aphid species representing efficient (M. persicae)
and inefficient (R. padi) vector species. For this, alatae were set free on
multiple occasions (10-15 repetitions each) amongst PSbMV-infected and mock
inoculated pea or faba bean (Vicia faba) plants. Following release, non
viruliferous R. padi alatae exhibited a general preference for PSbMV-infected pea
and faba bean plants after 30min-4h, but preferred mock-inoculated plants after
24h. In contrast, non-viruliferous M. persicae alatae alighted on mock-inoculated
pea plants preferentially for up to 48h following their release. With faba bean,
M. persicae preferred infected plants at the front of assay cages, but mock
inoculated ones their backs, apparently due to increased levels of natural light
there. When preliminary analyses were performed to detect PSbMV-induced changes
in the volatile organic compound profiles of pea and faba bean plants, higher
numbers of volatiles representing a range of compound groups (such as aldehydes,
ketones and esters) were found in the headspaces of PSbMV-infected than of mock
inoculated pea or faba bean plants. This indicates PSbMV induces physiological
changes in these hosts which manifest as altered volatile emissions. These
alterations could be responsible for the differences in alighting preferences.
Information from this study enhances understanding of virus-vector relationships
in the PSbMV-pea and faba bean pathosystems.
PMID- 28408209
TI - Role of miR-34a in TGF-beta1- and Drug-Induced Epithelial-Mesenchymal Transition
in Alveolar Type II Epithelial Cells.
AB - Epithelial-mesenchymal transition (EMT) of alveolar type II epithelial cells may
play an important role in the pulmonary fibrosis induced by drugs such as
bleomycin (BLM) and methotrexate (MTX). In this study, we examined the role of
microRNAs (miRNAs) in drug-induced EMT using RLE/Abca3, a cell line having
alveolar type II cell-like phenotype. Based on the screening using miRNA
microarray analysis, it was found that the expression of some miRNAs, such as miR
34a, was increased by transforming growth factor (TGF)-beta1 and BLM. An increase
in miR-34a expression due to TGF-beta1, BLM, and MTX was also observed in real
time PCR analysis. Therefore, miR-34a was focused upon in further studies. The
expression of nectin-1 mRNA and protein, a possible target of miR-34a, was
decreased by the treatment with TGF-beta1, BLM, and MTX. In addition, when
RLE/Abca3 cells were transfected with miR-34a mimic, the expression of nectin-1
mRNA and Abca3 mRNA, another target of miR34a, decreased significantly.
Furthermore, the mRNA expression of cytokeratin 19, an epithelial marker,
decreased, whereas that of alpha-smooth muscle actin, a mesenchymal marker,
increased in the cells transfected with miR-34a mimic. These results suggest that
miR-34a is involved in drug-induced EMT in alveolar epithelial cells, and
possibly in lung fibrosis.
PMID- 28408210
TI - The Organic Anion-Transporting Peptide 2B1 Is Localized in the Basolateral
Membrane of the Human Jejunum and Caco-2 Monolayers.
AB - The organic anion-transporting polypeptide (OATP) 2B1 which is ubiquitously
expressed in the human body is assumed to play an important role in the cellular
uptake of many drugs. Although the expression and function of this solute carrier
transporter is well characterized in the human liver and other tissues, little is
known about its localization and functional relevance in the intestine. Thus, it
was the aim of this study to investigate its localization and function in the
human jejunum and in the frequently used intestinal Caco-2 cell line. The
basolateral membrane of jejunal tissue from 6 individuals showed a significant
enrichment of OATP2B1 (17-fold) and the known basolateral proteins ABCC3 and Na/K
ATPase compared to the apical membrane as derived from targeted proteomics
analysis. On the contrary, apical localization could be confirmed for ABCB1,
ABCC2, and PEPT1. Basolateral localization of OATP2B1 could also be verified in
Caco-2 cells. Bidirectional transport studies with established OATP2B1 substrates
(sulfasalazine and pravastatin) across freshly exercised human jejunum and Caco-2
cell monolayers demonstrated a markedly higher transport from the basal to the
apical compartment than in the opposite direction. Our data provide evidence for
a basolateral localization of OATP2B1 which may improve our understanding of
intestinal drug absorption.
PMID- 28408211
TI - Cardiac voltage-gated ion channels in safety pharmacology: Review of the
landscape leading to the CiPA initiative.
AB - Voltage gated ion channels are central in defining the fundamental properties of
the ventricular cardiac action potential (AP), and are also involved in the
development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion
currents, including the Na+ current (INa), L-type Ca2+ current (Ica-L), and K+
currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner
that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and
S7B over a decade ago, there has been a focus on drug effects on QT prolongation
clinically, and on the rapidly activating delayed rectifier current (IKr),
nonclinically, for evaluation of proarrhythmic risk. This focus on QT interval
prolongation and a single ionic current likely impacted negatively some drugs
that lack proarrhythmic liability in humans. To rectify this issue, the
Comprehensive in vitro proarrhythmia assay (CiPA) initiative has been proposed to
integrate drug effects on multiple cardiac ionic currents with in silico
modelling of human ventricular action potentials, and in vitro data obtained from
human stem cell-derived ventricular cardiomyocytes to estimate proarrhythmic risk
of new drugs with improved accuracy. In this review, we present the physiological
functions and the molecular basis of major cardiac ion channels that contribute
to the ventricle AP, and discuss the CiPA paradigm in drug development.
PMID- 28408212
TI - Application of molecular imaging technology in evaluating the inhibiting effect
of apigenin in vivo on subcutaneous hepatocellular carcinoma.
AB - The aim of this study was to evaluate the inhibiting effect of apigenin on liver
cancer in vivo based on the optical molecular imaging method. Subcutaneous liver
tumor models were established using respective 1 * 106 firefly luciferase (fLuc)
and green fluorescent protein (GFP) labeled human hepatocellular carcinoma cells
(HepG2-fLuc and HepG2-GFP cells) in 20 BALB/c nude mice which were randomly
divided into two groups, 10 in each group. After the tumor cells were implanted
15 days, apigenin was administered through intraperitoneal injection in group B,
the other ten mice as control group A. Bioluminescence imaging (BLI) and
fluorescence molecular imaging (FMI) were carried out for the follow-up of
subcutaneous tumor model. As time goes on, intensity and distribution of
bioluminescence and fluorescence of tumours increased gradually with the growth
of tumours little by little. The whole process of observation was in accordance
with known activities of HCC in the human liver. The tumor volume and tumor
weight were significant lower in group B than in group A (p < 0.05), Subcutaneous
tumours in the apigenin treatment group B based on BLI and FMI were significantly
inhibited compared to the control group A (p < 0.05). Apigenin could be expected
as a new drug to treat hepatocellular carcinoma. Optical molecular imaging
technology enabled the non-invasive and reliable assessment of anti-tumor drug
efficacy on liver cancer.
PMID- 28408213
TI - Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard
Spectra(r), Merial) against adult Ancylostoma ceylanicum hookworm, in dogs.
AB - A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin
oxime (NexGard Spectra(r), Merial) was tested in purpose-bred Beagle dogs for
efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were
inoculated each by oral administration of approximately 500 infective larvae of
A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and
allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable
tablets or to remain untreated. Commercial chewable tablets of different strength
were combined to deliver doses as close as possible to the minimum effective dose
of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites
were recovered and counted for determination of efficacy seven days after
treatment. All eight dogs that had been left untreated were harboring adult A.
ceylanicum (geometric mean, 317.8; range, 210-428) while only one and nine A.
ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus
milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9%
efficacy against induced infection of A. ceylanicum was obtained by the use of
oral NexGard Spectra(r) at the minimum effective dose. Treatment with afoxolaner
plus milbemycin oxime chewable tablets was well accepted and safe.
PMID- 28408214
TI - Prevalence and genotypic characterization of bovine Echinococcus granulosus
isolates by using cytochrome oxidase 1 (Co1) gene in Hyderabad, Pakistan.
AB - Cystic echinococcosis is an important zoonotic disease; it has serious impacts on
animals as well as human health throughout the world. Genotypic characterization
of Echinocossus granulosus (E. granulosus) in buffaloes has not been addressed in
Pakistan. Therefore, the present study was conducted to evaluate the incidence
and genotypic characterization of bovine E. granulosus. Out of 832 buffaloes
examined, 112 (13.46%) were found infected. The favorable site for hydatid cyst
development was liver (8.65%) followed by lungs (4.80%). The rate of cystic
echinococcosis was found higher in females 14.43% than males 9.77%. The females
above seven years aged were more infected as compared to the young ones. The
partial sequence of mitochondrial cytochrome oxidase 1 (CO1) gene was used for
identification and molecular analysis of buffalo's E. granulosus isolates. The
alignment of redundant sequences were compared with already identified 10
genotypes available at National Centre for Biotechnology Information (NCBI)
GenBank. The sequencing and phylogenetic analysis of all randomly selected
buffalo isolates were belong to the G1- G3 complex (E. granulosus sensu stricto).
All sequences were diverse from the reference sequence. No one showed complete
identity to the buffalo strain (G3), representing substantial microsequence
variability in G1, G2 and G3 genotypes. We evaluated the echinococcal infectivity
and first time identification of genotypes in buffaloes in Sindh, Pakistan. This
study will lead to determine accurate source of this zoonotic disease to humans
in Pakistan.
PMID- 28408215
TI - Prevalence, genetic diversity and potential clinical impact of blood-borne and
enteric protozoan parasites in native mammals from northern Australia.
AB - A molecular survey was conducted to provide baseline information on the
prevalence, genetic diversity and potential clinical impacts of blood-borne and
enteric protozoans in native wild mammals from the Northern Territory (NT). A
total of 209 blood and 167 faecal samples were collected from four target
species; the northern brown bandicoot (Isoodon macrourus), common brushtail
possum (Trichosurus vulpecula), northern quoll (Dasyurus hallucatus) and brush
tailed rabbit-rat (Conilurus penicillatus). Blood samples were screened by PCR at
the 18S rRNA gene for trypanosomes, piroplasms and haemogregarines, with faecal
samples tested for Cryptosporidium spp. at the 18S rRNA locus, and for Giardia
spp. at the glutamate dehydrogenase (gdh) and 18S rRNA loci. The potential
clinical impact was investigated by associating clinical, haematological and
biochemical parameters with presence or absence of infection. Overall, 22.5% (95%
CI: 17.0-28.8%) of the animals tested were positive for haemoprotozoans.
Trypanosomes were found in 26.6% (95% CI: 18.7-35.7%) of the bandicoots and were
identified as Trypanosoma vegrandis G6, except for one unique genotype, most
similar to T. vegrandis G3 (genetic distance=7%). The prevalence of trypanosomes
in possums was 23.7% (95% CI: 11.4-40.2%), and the genotypes identified clustered
within the T. noyesi clade. The presence of Babesia sp. and Hepatozoon sp. was
confirmed in bandicoots only, both at a prevalence of 9.7% (95% CI: 2.7-9.2%).
The total prevalence of intestinal protozoan parasites observed was relatively
low (3%; 95% CI: 1.0-6.9%). No evidence of clinical disease associated with
protozoan parasitic infection was observed, however bandicoots positive for
Trypanosoma exhibited a significantly lower packed cell volume (PCV) compared to
negative bandicoots (p=0.046). To the authors' knowledge, this is the first
research conducted in the NT to characterise protozoan parasites in threatened
native mammals using both molecular and morphological tools; and to assess the
potential clinical impacts of these agents. The absence of clear signs of major
morbidity in infected animals seems to exclude a direct association between
infections with these agents and possible population decline events in northern
Australian native mammals. However until the cause(s) of population decline are
ascertained for each individual mammal species, further studies are required. The
outcome of the present investigation may be used to inform wildlife conservation
and zoonotic disease programs.
PMID- 28408216
TI - Modelling the impacts of pasture contamination and stocking rate for the
development of targeted selective treatment strategies for Ostertagia ostertagi
infection in calves.
AB - A simulation study was carried out to assess whether variation in pasture
contamination or stocking rate impact upon the optimal design of targeted
selective treatment (TST) strategies. Two methods of TST implementation were
considered: 1) treatment of a fixed percentage of a herd according to a given
phenotypic trait, or 2) treatment of individuals that exceeded a threshold value
for a given phenotypic trait. Four phenotypic traits, on which to base treatment
were considered: 1) average daily bodyweight gain, 2) faecal egg count, 3) plasma
pepsinogen, or 4) random selection. Each implementation method (fixed percentage
or threshold treatment) and determinant criteria (phenotypic trait) was assessed
in terms of benefit per R (BPR), the ratio of average benefit in weight gain to
change in frequency of resistance alleles R (relative to an untreated
population). The impact of pasture contamination on optimal TST strategy design
was investigated by setting the initial pasture contamination to 100, 200 or 500
O. ostertagi L3/kg DM herbage; stocking rate was investigated at a low
(3calves/ha), conventional (5 calves/ha) or high (7 calves/ha) stocking rates.
When treating a fixed percentage of the herd, treatments according to plasma
pepsinogen or random selection were identified as the most beneficial (i.e.
resulted in the greatest BPR) for all levels of initial pasture contamination and
all stocking rates. Conversely when treatments were administered according to
threshold values ADG was most beneficial, and was identified as the best TST
strategy (i.e. resulted in the greatest overall BPR) for all levels of initial
pasture contamination and all stocking rates.
PMID- 28408217
TI - Could mobile mammography reduce social and geographic inequalities in breast
cancer screening participation?
AB - Evaluation of mobile mammography for reducing social and geographic inequalities
in breast cancer screening participation. We examined the responses to first
invitations to undergo breast cancer screening from 2003 to 2012 in Orne, a
French department. Half of the participants could choose between screening in a
radiologist's office or a mobile mammography (MM) unit. We calculated the
participation rate and individual participation model according to age group,
deprivation quintile and distance. Among participants receiving an MM invitation,
the preference was for MM. This was especially the case in the age group >70years
and increased with deprivation quintile and remoteness. There were no significant
participation trends with regard to deprivation or remoteness. In the general
population, the influence of deprivation and remoteness was markedly diminished.
After adjustment, MM invitation was associated with a significant increase in
individual participation (odds ratio=2.9). MM can target underserved and remote
communities, allowing greater participation and decreasing social and geographic
inequalities in the general population. Proportionate universalism is an
effective principle for public health policy in reducing health inequalities.
PMID- 28408218
TI - Synthesis and biological evaluation of pyrimidine derivatives with diverse
azabicyclic ether/amine as novel GPR119 agonist.
AB - A class of novel pyrimidine derivatives bearing diverse conformationally
restricted azabicyclic ether/amine were designed, synthesized and evaluated for
their GPR119 agonist activities against type 2 diabetes. Most compounds exhibited
superior hEC50 values to endogenous lipid oleoylethanolamide (OEA). Analogs with
2-fluoro substitution in the aryl ring showed more potent GPR119 activation than
those without fluorine. Especially compound 27m synthesized from endo-azabicyclic
alcohol was observed to have the best EC50 value (1.2nM) and quite good agonistic
activity (112.2% max) as a full agonist.
PMID- 28408219
TI - Developing DYRK inhibitors derived from the meridianins as a means of increasing
levels of NFAT in the nucleus.
AB - A structure-activity relationship has been developed around the meridianin
scaffold for inhibition of Dyrk1a. The compounds have been focussed on the
inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT
in the nucleus. NFAT is responsible for up-regulation of genes responsible for
the induction of a slow, oxidative skeletal muscle phenotype, which may be an
effective treatment for diseases where exercise capacity is compromised. The SAR
showed that while strong Dyrk1a binding was possible with the meridianin scaffold
the compounds have no effect on NFAT localisation, however, by moving from the
indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT
residence time in the nucleus were obtained - properties not observed with the
reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo
muscle fiber assay. The increased biological activity is thought to arise from
the added interaction between the azaindole nitrogen and the lysine residue in
the back pocket.
PMID- 28408220
TI - First insight into structure-activity relationships of selective meprin beta
inhibitors.
AB - The astacin proteases meprin alpha and beta are emerging drug targets for
treatment of disorders such as kidney failure, fibrosis or inflammatory bowel
disease. However, there are only few inhibitors of both proteases reported to
date. Starting from NNGH as lead structure, a detailed elaboration of the
structure-activity relationship of meprin beta inhibitors was performed, leading
to compounds with activities in the lower nanomolar range. Considering the
preference of meprin beta for acidic residues in the P1' position, the compounds
were optimized. Acidic modifications induced potent inhibition and >100-fold
selectivity over other structurally related metalloproteases such as MMP-2 or
ADAM10.
PMID- 28408221
TI - Identification and structure activity relationship of novel flavone derivatives
that inhibit the production of nitric oxide and PGE2 in LPS-induced RAW 264.7
cells.
AB - In an effort to identify novel anti-inflammatory compounds, a series of flavone
derivatives were synthesized and biologically evaluated for their inhibitory
effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2),
representative pro-inflammatory mediators, in LPS-induced RAW 264.7 cells. Their
structure-activity relationship was also investigated. In particular, we found
that compound 3g displayed more potent inhibitory activities on PGE2 production,
similar inhibitory activities on NO production and less weak cytotoxicity than
luteolin, a natural flavone known as a potent anti-inflammatory agent.
PMID- 28408222
TI - Recent advances in the chemistry and biology of anti-inflammatory and specialized
pro-resolving mediators biosynthesized from n-3 docosapentaenoic acid.
AB - Several novel oxygenated polyunsaturated lipid mediators biosynthesized from n-3
docosapentaenoic acid were recently isolated from murine inflammatory exudates
and human primary cells. These compounds belong to a distinct family of
specialized pro-resolving mediators, and display potent in vivo anti-inflammatory
and pro-resolution effects. The endogenously formed specialized pro-resolving
mediators have attracted a great interest as lead compounds in drug discovery
programs towards the development of new classes of drugs that dampen inflammation
without interfering with the immune response. Detailed information on the
chemical structures, cellular functions and distinct biosynthetic pathways of
specialized pro-resolving lipid mediators is a central aspect of these biological
actions. Herein, the isolation, structural elucidation, biosynthetic pathways,
total synthesis and bioactions of the n-3 docosapentaenoic acid derived mediators
PD1n-3 DPA and MaR1n-3 DPA are discussed. In addition, a brief discussion of a
novel family of mediators derived from n-3 docosapentaenoic acid, termed 13
series resolvins is included.
PMID- 28408223
TI - Pharmacological property optimization for allosteric ligands: A medicinal
chemistry perspective.
AB - New strategies to potentially improve drug safety and efficacy emerge with
allosteric programs. Biased allosteric modulators can be designed with high
subtype selectivity and defined receptor signaling endpoints, however, selecting
the most meaningful parameters for optimization can be perplexing. Historically,
"potency hunting" at the expense of physicochemical and pharmacokinetic
optimization has led to numerous tool compounds with excellent pharmacological
properties but no path to drug development. Conversely, extensive physicochemical
and pharmacokinetic screening with only post hoc bias and allosteric
characterization has led to inefficacious compounds or compounds with on-target
toxicities. This field is rapidly evolving with new mechanistic understanding,
changes in terminology, and novel opportunities. The intent of this digest is to
summarize current understanding and debates within the field. We aim to discuss,
from a medicinal chemistry perspective, the parameter choices available to drive
SAR.
PMID- 28408224
TI - One drug for two targets: Biological evaluation of antiretroviral agents endowed
with antiproliferative activity.
AB - AIDS-related cancer diseases are malignancies with low incidence on healthy
people that affect mostly subjects already immunocompromised. The connection
between HIV/AIDS and these cancers has not been established yet, but a weakened
immune system is certainly the main cause. We envisaged the possibility to screen
a small library of compounds synthesized in our laboratory against opportunistic
tumors mainly due to HIV infection like Burkitt's Lymphoma. From cellular assays
and gene expression analysis we identified two promising compounds. These
derivatives have the dual action required inhibiting HIV replication in human TZM
bl cells infected with HIV-1 NL4.3 and showing cytotoxic activity on human colon
HT-29 and breast adenocarcinoma MCF-7 cells. In addition, preclinical in vitro
adsorption, distribution, metabolism, and excretion studies highlighted a
satisfactory pharmacokinetic profile.
PMID- 28408225
TI - Synthesis of isoflavene-thiosemicarbazone hybrids and evaluation of their anti
tumor activity.
AB - Phenoxodiol is an isoflavene with potent anti-tumor activity. In this study, a
series of novel mono- and di-substituted phenoxodiol-thiosemicarbazone hybrids
were synthesized via the condensation reaction between phenoxodiol with
thiosemicarbazides. The in vitro anti-proliferative activities of the hybrids
were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast
cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. The mono
substituted hybrids exhibited potent anti-proliferative activity against all
three cancer cell lines, while the di-substituted hybrids were less active.
Selected mono-substituted hybrids were further investigated for their
cytotoxicity against normal MRC-5 human lung fibroblast cells, which identified
two hybrids with superior selectivity for cancer cells over normal cells as
compared to phenoxodiol. This suggests that mono-substituted phenoxodiol
thiosemicarbazone hybrids have promising potential for further development as
anti-cancer agents.
PMID- 28408226
TI - Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa
inhibitors.
AB - Using structure based drug design, novel aminobenzisoxazoles as coagulation
factor IXa inhibitors were designed and synthesized. Highly selective inhibition
of FIXa over FXa was demonstrated. Anticoagulation profile of selected compounds
was evaluated by aPTT and PT tests. In vitro ADMET and pharmacokinetic (PK)
profiles were also evaluated.
PMID- 28408227
TI - Efficient and practical synthesis of Fondaparinux.
AB - Combining advantageous sequences of Alchemia and Sanofi methods of synthesis of
Fondaparinux, a more efficient and practical synthetic strategy for the synthesis
of corresponding protected pentasaccharide was developed. The protected
pentasaccharide was smoothly converted into Fondaparinux in overall high yield
(1%).
PMID- 28408228
TI - New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their
activity against herpes simplex virus type 1.
AB - Using the enzymatic transglycosylation reaction beta-d-ribo- and 2'
deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been
synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a
selective antiviral activity (selectivity index >32) against a wild strain of the
herpes simplex virus type 1, as well as towards virus strains that are resistant
to acyclovir, cidofovir, and foscarnet. We believe that this compound might be
used for treatment of herpes infections in those cases, when acyclovir is not
efficient.
PMID- 28408229
TI - Pharmacological evaluation of a novel series of urea, thiourea and guanidine
derivatives as P2X7 receptor antagonists.
AB - We report on P2X7 receptor antagonists based on a lead adamantly-cyanoguanidine
aryl moiety. We have investigated the importance of the central cyanoguanidine
moiety by replacing it with urea, thiourea or guanidine moieties. We have also
investigated the linker length between the central moiety and the aryl portion.
All compounds were assessed for their inhibitory potency in a pore-formation dye
uptake assay at the P2X7 receptor. None of the compounds resulted in an improved
potency illustrating the importance of the cyanoguanidine moiety in this
chemotype.
PMID- 28408231
TI - Japanese Immigrant with Abdominal Pain.
PMID- 28408230
TI - Discovery of LRRK2 inhibitors by using an ensemble of virtual screening methods.
AB - In this paper, we present the results of a ligand- and structure-based virtual
screen targeting LRRK2, a kinase that has been implicated in Parkinson's disease.
For the ligand-based virtual screen, the structures of 12 competitor compounds
were used as queries for a variety of 2D and 3D searches. The structure-based
virtual screen relied on homology models of LRRK2, as no X-ray structure is
currently available in the public domain. From the virtual screening, 662
compounds were purchased, of which 35 showed IC50 values below 10MUM in wild-type
and/or mutant LRRK2 (a hit rate of 5.3%). Of these 35 hits, four were deemed to
have potential for medicinal chemistry follow-up.
PMID- 28408232
TI - A Novel Case of Splenic Injury After Shockwave Lithotripsy.
AB - BACKGROUND: Emergency departments (EDs) are gateways for patients presenting
after minor surgical procedures, particularly shockwave lithotripsy.
Complications include renal and extrarenal tissue injuries, with the latter
having potentially serious consequences if not detected early. CASE REPORT: We
describe a 70-year-old male presenting to the ED for syncope. The patient
underwent shockwave lithotripsy (SWL) for left kidney stones 1 day prior. Upon
initial evaluation, the patient had normal vital signs and a normal physical
examination, without complaints of abdominal pain. Close observation and regular
patient re-evaluation led to the diagnosis of life-threatening injuries that
included splenic rupture. Although this is a rare complication of SWL, with only
eight published cases found in the literature, the patient's initial presentation
of syncope without complaints of abdominal pain presented a unique diagnostic
challenge. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency
physicians should be knowledgeable of the pre-existing conditions linked to
higher rates of complications after shockwave lithotripsy and be able to identify
and manage these potentially life-threatening complications.
PMID- 28408233
TI - Securing a Chest Tube Properly: A Simple Framework for Teaching Emergency
Medicine Residents and Assessing Their Technical Abilities.
AB - BACKGROUND: Quality-improvement efforts at our institution have identified chest
tube dislodgement as a preventable complication of tube thoracostomy. Because
proper fixation techniques are not well described in the literature and are
seldom formally taught, techniques vary among residents. OBJECTIVE: Our aim was
to develop and test a framework for teaching and assessing chest tube securement.
METHODS: A repeated-measures study design was used. At baseline, 19 emergency
medicine residents (program years 1-3) placed and secured a chest tube in a
cadaver. After a 45-min proficiency-based teaching session using a low-cost chest
tube simulator (approximate cost, $5), each resident again placed and secured a
chest tube in a cadaver, followed by 3-month retention testing. All securements
were evaluated by two raters using a four-point checklist and a five-point global
assessment scale (GAS). The checklist addressed suture selection, tying knots
down to the tube, wound approximation, and tube displacement relative to skin.
RESULTS: After the initial educational intervention, median scores for the group
improved significantly over baseline for the GAS (p < 0.001), checklist (p <
0.001), and amount of displacement (p = 0.01). At 3 months, GAS, checklist, and
displacement scores did not differ significantly from the immediate post-test
scores. Inter-rater reliability was substantial, with weighted kappa values of
.77 for the GAS and .70 for the checklist. CONCLUSIONS: Quality of chest tube
securement by emergency medicine residents can be significantly improved with an
inexpensive chest tube simulator and a brief workshop. The four-point checklist
served as a reliable and effective means for teaching and assessing chest tube
securement.
PMID- 28408234
TI - The Acute Hemolytic Anemias: The Importance of Emergency Diagnosis and
Management.
AB - BACKGROUND: Hemolytic anemias are defined by the premature destruction of red
blood cells. These anemias have many causes that are mostly due to chronic
diseases, but, occasionally, cases of acute life-threatening hemolysis can occur.
OBJECTIVE: The objectives of this article were to review the pathophysiology of
hemolytic anemias, to discuss the general emergency department (ED) evaluation,
and to discuss the assessment and treatment of important and "cannot miss"
hemolytic diseases. DISCUSSION: Because hemolytic anemias are rarely seen, the
emergency physician may consider a patient's anemia as due to blood loss rather
than hemolysis, and the workup and treatment may not be appropriate. The primary
goal for the emergency provider is to resuscitate, but he or she also must
recognize that a hemolytic process is present. Appropriate laboratory work and
specialist consultation should be obtained. While focused treatment is rarely
necessary in the ED, the avoidance of certain treatments, such as early platelet
transfusion in thrombotic thrombocytopenic purpura, may be necessary.
CONCLUSIONS: Hemolytic anemias are rare, but should still be considered in the ED
differential diagnosis of low hemoglobin. Emergency physicians should first
resuscitate, but should also be able to identify the presence of hemolysis and
obtain the appropriate laboratory tests. Occasionally, specific treatments are
needed but should be discussed in conjunction with a specialist.
PMID- 28408235
TI - Danger Triangle of Face and Septic Cavernous Sinus Thrombosis.
PMID- 28408236
TI - Unintentional Pediatric Cocaine Exposures Result in Worse Outcomes than Other
Unintentional Pediatric Poisonings.
AB - BACKGROUND: Unintentional pediatric cocaine exposures are rare but concerning due
to potentially serious complications such as seizures, dysrhythmias, and death.
OBJECTIVES: The objectives were to assess the demographic and clinical
characteristics of pediatric cocaine exposures reported to the California Poison
Control System. METHODS: This is a retrospective study of all confirmed pediatric
(< 6 years of age) cocaine exposures reported to the California Poison Control
System from January 1, 1997-September 30, 2010. Case narratives were reviewed for
patient demographics, exposure details, clinical effects, therapy,
hospitalization, and final outcome. RESULTS: Of the 86 reported pediatric cocaine
exposures, 36 had positive urine drug testing and were included in the study
cohort. The median age at presentation was 18 months (range: 0-48 months), and
56% were male (n = 20). The most common clinical manifestations were tachycardia
and seizures. The most common disposition was admission to an intensive care unit
(n = 14; 39%). Eleven cases (31%) were classified as having a major effect as per
American Association of Poison Control Centers case coding guidelines. One child
presented in asystole with return of spontaneous circulation after
cardiopulmonary resuscitation and multiple vasoactive medications. The proportion
of cocaine exposures with serious (moderate or major) outcomes (66.7%; 95%
confidence interval 50.3-79.8%) was higher than other pediatric poisonings
reported to the American Association of Poison Control Centers during the study
period (0.88%; 95% confidence interval 0.87-0.88). CONCLUSIONS: Although
pediatric cocaine exposures are rare, they result in more severe outcomes than
most unintentional pediatric poisonings. Practitioners need to be aware of the
risk of recurrent seizures and cardiovascular collapse associated with cocaine
poisoning.
PMID- 28408237
TI - Habituation and adaptation to odors in humans.
AB - Habituation, or decreased behavioral response, to odors is created by repeated
exposure and several detailed characteristics, whereas adaptation relates to the
neural processes that constitute this decrease in a behavioral response. As with
all senses, the olfactory system continually encounters an enormous variety of
odorants which is why mechanisms must exist to segment them and respond to
changes. Although most olfactory habitation studies have focused on animal
models, this non-systematic review provides an overview of olfactory habituation
and adaptation in humans, and techniques that have been used to measure them.
Thus far, psychophysics in combination with modern techniques of neural
measurement indicate that habituation to odors, or decrease of intensity, is
relatively fast with adaptation occurring more quickly at higher cerebral
processes than peripheral adaptation. Similarly, it has been demonstrated that
many of the characteristics of habitation apply to human olfaction; yet, evidence
for some characteristics such as potentiation of habituation or habituation of
dishabituation need more support. Additionally, standard experimental designs
should be used to minimize variance across studies, and more research is needed
to define peripheral-cerebral feedback loops involved in decreased responsiveness
to environmental stimuli.
PMID- 28408238
TI - Novel roles for podocalyxin in regulating stress myelopoiesis, Rap1a, and
neutrophil migration.
AB - Podocalyxin (Podxl) is a CD34 orthologue and cell surface sialomucin reported to
have roles in renal podocyte diaphragm slit development; vascular cell integrity;
and the progression of blood, breast, and prostate cancers. Roles for Podxl
during nonmalignant hematopoiesis, however, are largely undefined. We have
developed a Vav-Cre Podxl knockout (KO) mouse model, and report on novel roles
for Podxl in governing stress myelopoiesis. At steady state, Podxl expression
among hematopoietic progenitor cells was low level but was induced by granulocyte
colony-stimulating factor (G-CSF) in myeloid progenitors and by thrombopoietin in
human stem cells. In keeping with low-level Podxl expression at steady state, Vav
Cre deletion of Podxl did not markedly alter peripheral blood cell levels. A G
CSF challenge in Podxl-KO mice, in contrast, hyperelevated peripheral blood
neutrophil and monocyte levels. Podxl-KO also substantially heightened neutrophil
levels after 5-fluorouracil myeloablation. These loss-of-function phenotypes were
selective, and Podxl-KO did not alter lymphocyte, basophil, or eosinophil levels.
Within bone marrow (and after G-CSF challenge), Podxl deletion moderately
decreased colony forming units-granulocytes, eyrthrocytes, monocyte/macrophages,
megakaryocytes and CD16/32posCD11bpos progenitors but did not affect Gr-1pos cell
populations. Notably, Podxl-KO did significantly heighten peripheral blood
neutrophil migration capacities. To interrogate Podxl's action mechanisms, a co
immunoprecipitation plus liquid chromatography-mass spectrometry approach was
applied using hematopoietic progenitors from G-CSF-challenged mice. Rap1a, a Ras
related small GTPase, was a predominant co-retrieved Podxl partner. In bone
marrow human progenitor cells, Podxl-KO led to heightened G-CSF activation of
Rap1aGTP, and Rap1aGTP inhibition attenuated Podxl-KO neutrophil migration.
Studies have revealed novel roles for Podxl as an important modulator of
neutrophil and monocyte formation and of Rap1a activation during stress
hematopoiesis.
PMID- 28408239
TI - Protective responses of two paralogs of granulocyte colony stimulating factor
(GCSF) in rock bream, Oplegnathus fasciatus during bacterial and viral infection.
AB - Granulocyte colony stimulating factor (GCSF) has a key role in the production of
neutrophilic granulocytes during normal hematopoietic development and release of
neutrophils into the blood circulation. In this study we have identified and
characterized two paralogs of GCSF (RbGCSF) in rock bream. Although RbGCSF-1 and
RbGCSF-2 share low sequence conservation, its domains and protein structure still
share significant similarity. Basal levels of RbGCSF-1 gene expression was high
in peripheral blood leukocytes (PBLs), spleen and intestine whereas the RbGCSF-2
was highly expressed in PBLs and kidney, of healthy animals. A significant
induction of RbGCSFs were observed after the challenge with Streptococcus iniae
in kidney, spleen and gills during initial hours of infection. Whereas
Edwarsiella tarda infection caused a reasonable expression in kidney. Red
seabream iridovirus caused induction of RbGCSF-1 transcription only in gills
during initial hours. This higher expression of RbGCSF in early hours may be its
response to induce emergency hematopoiesis, due to shortage of neutrophils to
combat the surge in pathogens. The difference in induction of RbGCSF paralogs
during infection may constitute to its different roles or overlapping functions.
PMID- 28408240
TI - Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling
of Multiple Spatially Separated Samples within Tumors.
AB - Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant
pathways in kidney cancer are elevated, with frequent mutation of the VHL gene.
Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer.
However, intratumor metabolic heterogeneity has not been investigated. Here, we
used global metabolomics analysis and tissue slice tracer studies to demonstrate
that different portions of a human primary kidney tumor possess different
metabolic characteristics and drug sensitivity. Pyruvate levels were elevated and
pyruvate metabolism was altered in some tumor sections. These observations
indicated that pyruvate metabolism may constitute a possible vulnerability of
kidney cancer; indeed, pyruvate stimulated the growth of primary kidney cancer
cells and pharmacological inhibition of pyruvate transporters slowed the growth
of patient-derived kidney tumors in mice. These findings deepen our understanding
of the intratumor metabolic heterogeneity of kidney cancer and may inform novel
therapeutic approaches in human kidney cancer.
PMID- 28408241
TI - Maternal Retinoids Increase PDGFRalpha+ Progenitor Population and Beige
Adipogenesis in Progeny by Stimulating Vascular Development.
AB - Maternal vitamin A intake varies but its impact on offspring metabolic health is
unknown. Here we found that maternal vitamin A or retinoic acid (RA)
administration expanded PDGFRalpha+ adipose progenitor population in progeny,
accompanied by increased blood vessel density and enhanced brown-like (beige)
phenotype in adipose tissue, protecting offspring from obesity. Blockage of
retinoic acid signaling by either BMS493 or negative RA receptor (RARalphaDN)
over-expression abolished the increase in blood vessel density, adipose
progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA
induced beige adipogenesis was blocked following vascular endothelial growth
factor receptor (VEGFR) 2 knock out in PDGFRalpha+ cells, suggesting its
mediatory role. Our data reveal an intrinsic link between maternal retinoid level
and offspring health via promoting beige adipogenesis. Thus, enhancing maternal
retinoids is an amiable therapeutic strategy to prevent obesity in offspring,
especially for those born to obese mothers which account for one third of all
pregnancies.
PMID- 28408242
TI - Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection.
AB - Influenza is a highly contagious, acute, febrile respiratory infection that can
have fatal consequences particularly in individuals with chronic illnesses.
Sporadic reports suggest that intravenous immunoglobulin (IVIg) may be
efficacious in the influenza setting. We investigated the potential of human IVIg
to ameliorate influenza infection in ferrets exposed to either the pandemic
H1N1/09 virus (pH1N1) or highly pathogenic avian influenza (H5N1). IVIg
administered at the time of influenza virus exposure led to a significant
reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model,
the majority of animals given IVIg survived challenge in a dose dependent manner.
Protection was also afforded by purified F(ab')2 but not Fc fragments derived
from IVIg, supporting a specific antibody-mediated mechanism of protection. We
conclude that pre-pandemic IVIg can modulate serious influenza infection
associated mortality and morbidity. IVIg could be useful prophylactically in the
event of a pandemic to protect vulnerable population groups and in the critical
care setting as a first stage intervention.
PMID- 28408244
TI - US pollution policy up in the air.
PMID- 28408243
TI - Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer
and activating EGFR mutations (BELIEF): an international, multicentre, single
arm, phase 2 trial.
AB - BACKGROUND: The tyrosine kinase inhibitor erlotinib improves the outcomes of
patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal
growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance
mutation with another EGFR mutation in treatment-naive patients has been
associated with a shorter progression-free survival to EGFR inhibition than in
the absence of the T790M mutation. To test this hypothesis clinically, we
developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were
treated with the combination of erlotinib and bevacizumab, stratified by the
presence of the pretreatment T790M mutation. METHODS: BELIEF was an
international, multicentre, single-arm, phase 2 trial done at 29 centres in eight
European countries. Eligible patients were aged 18 years or older and had
treatment-naive, pathologically confirmed stage IIIB or stage IV lung
adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or
L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous
bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment
T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR.
The primary endpoint was progression-free survival. The primary efficacy analysis
was done in the intention-to-treat population and was stratified into two
parallel substudies according to the centrally confirmed pretreatment T790M
mutation status of enrolled patients (T790M positive or negative). The safety
analysis was done in all patients that have received at least one dose of trial
treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028.
FINDINGS: Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and
included in the efficacy analysis. 37 patients were T790M mutation positive and
72 negative. The overall median progression-free survival was 13.2 months (95% CI
10.3-15.5), with a 12 month progression-free survival of 55% (95% CI 45-64). The
primary endpoint was met only in substudy one (T790M-positive patients). In the
T790M-positive group, median progression-free survival was 16.0 months (12.7 to
not estimable), with a 12 month progression-free survival of 68% (50-81), whereas
in the T790M-negative group, median progression-free survival was 10.5 months
(9.4-14.2), with a 12 month progression-free survival of 48% (36-59). Of 106
patients included in the safety analysis, five had grade 4 adverse events (one
acute coronary syndrome, one biliary tract infection, one other neoplasms, and
two colonic perforations) and one died due to sepsis. INTERPRETATION: The BELIEF
trial provides further evidence of benefit for the combined use of erlotinib and
bevacizumab in patients with NSCLC harbouring activating EGFR mutations. FUNDING:
European Thoracic Oncology Platform, Roche.
PMID- 28408245
TI - Combined bevacizumab and erlotinib treatment in patients with lung cancer with
the T790M resistance mutation.
PMID- 28408246
TI - Renal protective effect and action mechanism of Huangkui capsule and its main
five flavonoids.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Abelmoschus manihot (Linn.) Medicus
(A. manihot), as a traditional Chinese Herbal medicine, was used widely in China
with efficacy of inducing diuresis for treating strangurtia, and subdhing
swelling and detoxicating. It has been reported that Huangkui capsule, prepared
by the extract of the flower of A. manihot, can reduce the content of urinary
protein, serum creatinine and serum urea nitrogen in nephropathy rats and
processes renoprotective activity, while the action mechanism need to illuminate
deeply. AIMS OF THE STUDY: In this study, we investigated the protection effect
of Huangkui capsule on tubulointerstitial fibrosis in chronic renal failure (CRF)
rats and its mechanism against high glucose-induced epithelial to mesenchymal
transition (EMT) in renal tubular epithelial cells (HK-2) of its bioactive
components. MATERIALS AND METHODS: The animals were divided into normal group,
CRF model group and Huangkui capsule-treated group. Hematoxylin eosin (HE)
staining and Masson staining were applied to observe pathological changes in
renal tissue of different groups. Biochemical indicators including serum urea
nitrogen (BUN), urine protein (UP) and serum creatinine (Scr) were measured
according to the manufacturer's instructions of kits. HK-2 cell damaged model was
established to access the protection effect and action mechanism of five main
flavonoids from Huangkui capsule. The experimental cells were divided into eight
groups: control group, model group, positive drug group and five main flavonoids
treated groups. The dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used
to determine the reactive oxygen species (ROS) in different groups. Western blot
was applied to analyze the expression of pathogenesis-related proteins in
different groups. RESULTS: The results stated that Huangkui capsule significantly
inhibited the elevation of Scr, BUN, UP, the expression of alpha-smooth muscle
actin (alpha-SMA), phosphorylation-extracellular signal-regulated kinase (p
ERK1/2), NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in adenine-induced
CRF rats. The main bioactive components of quercetin (QT), hyperoside (HY),
isoquercitrin (IQT), gossypetin-8-O-beta-D-glucuronide (GG) and quercetin-3'-O
glucoside (QG) at the dosage of 100uM, like NADPH oxidase inhibitor
diphenyleneiodonium, exhibited a significant effect on inhibiting the expression
of alpha-SMA, p-ERK1/2, NADPH Oxidase 1, NADPH Oxidase 2 and NADPH Oxidase 4 in
high glucose-induced HK-2 cells, especially GG. CONCLUSIONS: These results
demonstrated that Huangkui capsule and the flavonoids components prevent
tubulointerstitial fibrosis in CRF rat involvement in the action mechanism of
inhibiting NADPH oxidase/ROS/ERK pathway.
PMID- 28408247
TI - Absence of PTHrP nuclear localization and C-terminus sequences leads to abnormal
development of T cells.
AB - Parathyroid hormone-related protein (PTHrP), a ubiquitously expressed protein, is
composed of four functional domains including N-terminus, mid region, nuclear
localization signal (NLS) and C-terminus. Under the direction of NLS, PTHrP can
enter cell nucleus from cytoplasm and stimulate mitogenesis. Although PTHrP is
considered to have important developmental roles, the role of PTHrP NLS and C
terminus in developmental process remains unknown, especially in T-cell
development. Here, we used a knock-in mouse model, which expresses a truncated
form of PTHrP missing the NLS (87-107) and C-terminus (108-139) of the protein,
to examine the role of PTHrP NLS and C-terminus in T-cell development. Our
results showed that the truncated PTHrP (1-84) led to abnormal subpopulations,
impaired proliferation and increased apoptosis in the thymus, indicating that
PTHrP is involved in the development of T cells, and the NLS and C-terminus part
is necessary for the normal role of PTHrP in T-cell development.
PMID- 28408248
TI - Extraforaminal compression of the L5 nerve: An anatomical study with application
to failed posterior decompressive procedures.
AB - This anatomical study was performed to elucidate the pertinent foraminal and
lateral L5 nerve anatomy to enhance our understanding of possible neurologic
causes of failed decompression surgery. Persistent extraforaminal L5 nerve
compression is a possible cause of persistent symptoms following lumbosacral
surgery. The amount of extraforaminal space for the L5 ventral ramus was examined
in fifty adult human skeletons (100 sides). Based on morphology, the specimens
were then categorized (types I-IV) on the basis of the bony space available for
the nerve at this location. Next, 25 embalmed adult cadavers (50 sides) underwent
bilateral dissection of the lower lateral lumbar region. The type of bony
extraforaminal outlet was documented for each cadaver on the basis of our
skeletal analysis. Lastly, segments (intra- and extra-foraminal) of the L5
ventral ramus were excised and examined histologically. Types I-IV outlets were
found in 43, 31, 20 and 6 skeletal sides, respectively. For cadavers, 22,15, 10
and 3 sides were found to have types I-IV bony outlets, respectively. In
cadavers, all type IV outlets and 70% of the type III bony configurations
adjacent to the L5 ventral ramus had signs of neural irritation/injury including
vascular hyalinization and increased fibrosis distal to the intervertebral
foramen. No distal segments of type I and type II outlets showed histological
signs of neural compromise. Patients with symptoms referable to L5 nerve
compression for whom no proximal pathology is identified could warrant
investigation of the more distal extraforaminal segment of this nerve.
PMID- 28408249
TI - Temozolomide does not influence the transcription or activity of matrix
metalloproteinases 9 and 2 in glioma cell lines.
AB - Glioblastoma multiforme (GBM) is a treatment-resistant malignancy with poor
prognosis. Temozolomide (TMZ) is widely used as a first-line drug for GBM.
Although this improves patient prognosis, it does not completely eradicate the
tumour. Even after total surgical resection, GBM can exhibit uncontrollable
invasiveness at the tumour margins owing to activation of matrix
metalloproteinases (MMPs) such as MMP-2 and -9; these degrade collagen IV in the
basement membrane, which normally prevents cancer invasion. TMZ induces DNA
damage and activates transcription factors including c-jun, c-fos, nuclear factor
kappabeta, and early growth response protein-1, which have putative binding sites
on the MMP-9 promoter. TMZ may therefore enhance tumour invasion by stimulating
MMP-9 transcription and enzymatic activity. To test this hypothesis, we
investigated MMP-2 and -9 mRNA transcription and activity in GBM cell lines
treated with TMZ. Human A172 GBM cells were exposed to TMZ (25% and 50%
inhibitory concentrations) for 24 or 48h; cell cycle distribution and mRNA levels
of MMP-2 and -9 were evaluated using flow cytometry and semi-quantitative reverse
transcription PCR, respectively. MMP-2 and -9 enzymatic activities were assessed
using gelatin zymography in human A172 and U373 MG GBM cells exposed to TMZ under
the same conditions. TMZ altered A172 cell cycle distribution, but not MMP-2 or
9 mRNA levels. TMZ did not affect MMP-2 or -9 enzymatic activities in A172 or
U373 MG cells. These findings indicated that TMZ is therefore unlikely to promote
GBM invasiveness.
PMID- 28408250
TI - International Society for Infectious Diseases: Position statement on the March
for Science, April 22, 2017.
PMID- 28408251
TI - A 34-Year-Old Obese Woman with Rash, Finger Swelling and Fever.
AB - Disseminated tuberculosis first presenting as cutaneous lesion is uncommon and
difficult to diagnose on account of its divers clinical forms. We present a 34
year-old obese woman with rash, finger swelling and fever. The patient was
firstly manifested by fever and mass in palm and finger, gradually involving
multisystems injury. She was diagnosed with disseminated tuberculosis in
consideration of multiple system involvement, imaging characteristics,
tuberculous granuloma in dermis and positive result of Mycobacterium culture.
After two months of anti-tuberculosis treatment, fever and multisystems injury
were controlled effectively, but skeletal and bone marrow involvement continued
to progress, experiencing tuberculosis related acute hematopoietic stagnation.
Continuing intensive therapy to one year, skeletal and hematological involvement
improved and treatment was discontinued after two years. Follow-up to now with
drug withdrawal for more than 1year, the patient remains in remission.
PMID- 28408252
TI - Israeli Spotted Fever in Sicily. Description of two cases and minireview.
AB - Mediterranean spotted fever (MSF) is endemic in Italy, where Rickettsia conorii
subsp. conorii was thought to be the only pathogenic rickettsia and Rhipicephalus
sanguineus the vector and main reservoir. R. conorii subsp. israelensis, which
belongs to the R. conorii complex, is the agent of Israeli spotted fever (ISF);
apart from Israel, it has also been found in Italy (Sicily and Sardinia) and in
different regions of Portugal. We describe here two severe cases of ISF which
occurred in otherwise healthy Italian adults. Their characteristics are analyzed
and discussed in the light of other 91 cases found through a systematic review of
international literature.
PMID- 28408253
TI - Humanized chimeric mouse models of hepatitis B virus infection.
AB - Hepatitis B virus (HBV) infection is associated with an increased risk of hepatic
cirrhosis, hepatocellular carcinoma, fulminant hepatitis and end-stage hepatic
failure. Despite the availability of anti-HBV therapies, HBV infection remains a
major global public health problem. Developing an ideal animal model of HBV
infection to clarify the details of the HBV replication process, the viral life
cycle, the resulting immunoresponse and the precise pathogenesis of HBV is
difficult because HBV has an extremely narrow host range and almost exclusively
infects humans. In this review, we summarize and evaluate animal models available
for studying HBV infection, especially focusing on humanized chimeric mouse
models, and we discuss future development trends regarding immunocompetent
humanized mouse models that can delineate the natural history and
immunopathophysiology of HBV infection.
PMID- 28408254
TI - Midterm outcomes of bone grafting in glenoid defects treated with reverse
shoulder arthroplasty.
AB - BACKGROUND: Large glenoid defects are a difficult reconstructive problem for
shoulder surgeons. The purpose of this study was to determine the complications,
rate of healing, and functional results of glenoid bone grafting in primary or
revision surgery with reverse shoulder arthroplasty. METHODS: We retrospectively
reviewed 23 patients with glenoid bone loss who underwent primary or revision
surgery using a glenoid bone graft with a minimum follow-up of 2 years. Range of
motion and the Constant, American Shoulder and Elbow Surgeons, and visual analog
scale scores were obtained from preoperative assessment and the latest follow-up
visit. Radiographic evaluation included analysis of plain radiographs as well as
preoperative and follow-up computed tomography. RESULTS: Three patients were
excluded from the study. Allografts were used in 13 cases and autografts in 7
cases. The mean Constant score improved from 30.7 +/- 9.4 to 51.3 +/- 13.4 (P <
.001). At a mean follow-up of 26 months, computed tomography imaging revealed
that the glenoid bone graft was fully incorporated in 95% of cases. No
statistically significant differences were found on analysis of the clinical and
radiographic outcomes related to the graft source. There was a 20% postoperative
complication rate: 1 case of aseptic glenoid component loosening, 1 surgical
wound hematoma, 1 acromial fracture, and a symptomatic grade 3 scapular notching.
CONCLUSIONS: The use of bone grafts in glenoid defects is a useful technique by
which, in the majority of cases, single-stage reconstruction surgery may be
performed, even in the presence of severe bone loss. Incorporation rates are
high, with satisfactory clinical outcome.
PMID- 28408255
TI - Supraorbital Versus Endoscopic Endonasal Approaches for Olfactory Groove
Meningiomas: A Cost-Minimization Study.
AB - OBJECTIVE: To perform a cost-minimization study comparing the supraorbital and
endoscopic endonasal (EEA) approach with or without craniotomy for the resection
of olfactory groove meningiomas (OGMs). METHODS: We built a decision tree using
probabilities of gross total resection (GTR) and cerebrospinal fluid (CSF) leak
rates with the supraorbital approach versus EEA with and without additional
craniotomy. The cost (not charge or reimbursement) at each "stem" of this
decision tree for both surgical options was obtained from our hospital's finance
department. After a base case calculation, we applied plausible ranges to all
parameters and carried out multiple 1-way sensitivity analyses. Probabilistic
sensitivity analyses confirmed our results. RESULTS: The probabilities of GTR
(0.8) and CSF leak (0.2) for the supraorbital craniotomy were obtained from our
series of 5 patients who underwent a supraorbital approach for the resection of
an OGM. The mean tumor volume was 54.6 cm3 (range, 17-94.2 cm3). Literature
reported rates of GTR (0.6) and CSF leak (0.3) with EEA were applied to our
economic analysis. Supraorbital craniotomy was the preferred strategy, with an
expected value of $29,423, compared with an EEA cost of $83,838. On multiple 1
way sensitivity analyses, supraorbital craniotomy remained the preferred
strategy, with a minimum cost savings of $46,000 and a maximum savings of
$64,000. Probabilistic sensitivity analysis found the lowest cost difference
between the 2 surgical options to be $37,431. CONCLUSION: Compared with EEA,
supraorbital craniotomy provides substantial cost savings in the treatment of
OGMs. Given the potential differences in effectiveness between approaches, a cost
effectiveness analysis should be undertaken.
PMID- 28408256
TI - Diabetes: Is It the Troublemaker in Anterior Cervical Discectomy and Fusion?
PMID- 28408257
TI - Ischemic Stroke in Young Adults with Moyamoya Disease: Prognostic Factors for
Stroke Recurrence and Functional Outcome after Revascularization.
AB - OBJECTIVE: Stroke in young adults is uncommon and rarely described. Moyamoya
disease is one of the leading causes of stroke in young adults. We aimed to study
the prognostic factors for stroke recurrences and functional outcomes in young
stroke patients with moyamoya disease after revascularization. METHODS: We
reviewed 696 consecutive patients with moyamoya disease admitted to our hospital
from 2009-2015 and identified patients aged 18-45 years with first-ever stroke.
Follow-up was conducted via face-to-face or structured telephone interviews.
Outcome measures were recurrent stroke events and unfavorable functional outcomes
(modified Rankin Scale >2). RESULTS: We included 121 young patients with moyamoya
disease suffering from stroke (initial presentation age, 35.4 +/- 7.5 years). All
patients underwent revascularization after the acute phase of initial stroke
events as the secondary prevention for recurrences. During follow-up (median, 40
months), 9 patients (7.4%) experienced recurrent strokes and 8 of them (6.6%)
suffered unfavorable functional outcomes. In the multivariate analysis, diabetes
was an independent predictor for stroke recurrences (hazard ratio 6.76; 95%
confidence interval 1.30-35.11; P = 0.02) and was significantly associated with
unfavorable functional outcomes (odds ratio 7.87; 95% confidence interval 1.42
38.74; P = 0.01). CONCLUSIONS: We identified diabetes as an independent risk
factor for recurrent strokes and unfavorable functional outcomes after
revascularization in young stroke patients with moyamoya disease.
PMID- 28408258
TI - Predictors of Postoperative Cerebral Ischemia in Patients with Ruptured Anterior
Communicating Artery Aneurysms.
AB - OBJECTIVE: Cerebral ischemia is a major contributor to poor outcome after
ruptured anterior communicating artery aneurysms (ACoAs), and is not well
classified. In this article, we develop a classification and identify risk
factors of cerebral ischemia after ruptured ACoAs. METHODS: Three hundred sixty
patients with ruptured ACoAs undergoing microsurgical clipping were collected.
Sex, age, smoking status, Hunt-Hess grade, Fisher grade, hospital stay, surgical
timing, hypertension, diabetes, postoperative cerebral ischemia, and
postoperative modified Rankin Scale score were collected. Postoperative ischemic
changes are classified according to a novel grade (ischemic grade I-IV). RESULTS:
Predictive factors of postoperative ischemia (grade I-IV) included sex (odds
ratio [OR], 1.956; 95% confidence interval [CI], 1.262-3.032; P = 0.003) and
Fisher grade (OR, 1.813; 95% CI, 1.144-2.871; P = 0.011). Male sex had a tendency
to develop postoperative cerebral ischemia (61.3% in the ischemia group vs. 45.7%
in the nonischemia group), while surgical timing did not. However, in patients
with postoperative ischemia, early surgery within 3 days (OR, 3.334; 95% CI,
1.411-7.879; P = 0.006) and advanced age greater than 55 years (OR, 2.783; 95%
CI, 1.214-6.382; P = 0.016) were risk factors for postoperative neurologic
deficits (grade III-IV). CONCLUSIONS: Male sex and higher Fisher grade predict
postoperative ischemia (grade I-IV), whereas surgical timing does not. However,
in patients with postoperative cerebral ischemia, early surgery within 3 days and
age greater than 55 years can increase the frequency of postoperative
neurological deficits (grade III-IV). Older male patients undergoing early
microsurgery had a tendency to develop neurologic deficits.
PMID- 28408260
TI - Evaluation of Bioabsorbable Multiamino Acid Copolymer/Nanohydroxyapatite/Calcium
Sulfate Cage in a Goat Spine Model.
AB - BACKGROUND: Currently, polylactide is the most popular material used to made
bioabsorbable cages but too-quick degradation and osteolysis around the cage have
been reported in the literature. This study evaluated the fusion effect,
biomechanical stability, and histologic characteristics of a novel bioabsorbable
multiamino acid copolymer/nanohydroxyapatite/calcium sulfate (MAACP/n-HA/CS)
interbody cage in a goat model of anterior cervical discectomy and fusion.
METHODS: A total of 24 goats underwent C3/C4 discectomy and fusion with 3 groups
of intervertebral implants: MAACP/n-HA/CS cage group (n = 8), titanium cage group
(n = 8), and autologous tricortical iliac crest bone group (n = 8). Disc space
height and lordosis angle were measured pre- and postoperatively and after 4, 12,
and 24 weeks. Range of motion (ROM) was evaluated through biomechanical testing.
Histologic analysis was performed to evaluate fusion status and to detect any
foreign body reactions associated with the bioabsorbable cages. RESULTS: At 12
and 24 weeks, disc space height in MAACP/n-HA/CS cage group was greater than that
of titanium cage group and tricortical iliac crest group (P < 0.05). Lordosis
angle in MAACP/n-HA/CS cage group and titanium cage group were lower than that of
tricortical iliac crest group (P < 0.05). Biomechanical test showed that ROM did
not differ significantly between MAACP/n-HA/CS cage group and titanium cage
group, whereas the value of ROM in bone graft group was the largest. Histologic
evaluation showed a better interbody fusion in the MAACP/n-HA/CS cage group than
in the other 2 groups. MAACP/n-HA/CS cage surface degraded and was absorbed at 24
weeks. All MAACP/n-HA/CS cages showed excellent biocompatibility. CONCLUSIONS:
MAACP/n-HA/CS cages can provide good fusion effect, enough biomechanical
stability, and integrate closely with the surrounding bone.
PMID- 28408261
TI - Use of Intraoperative Navigation for Reconstruction of the C1 Lateral Mass After
Resection of Aneurysmal Bone Cyst.
AB - BACKGROUND: Aneurysmal bone cysts (ABCs) are rare blood-filled cystic lesions
that are found in the long bones and spine. Here, we present a case of an ABC
found in the lateral mass and lamina of C1. Lesions in this area provide a
surgical challenge because of its difficulty to access as well as its need for
reconstruction. We describe a novel use of intraoperative navigation (ION) to
assist in the placement of a C1 lateral mass titanium cage. CASE DESCRIPTION: An
18-year-old female patient presented with headaches and progressive neck pain.
Imaging revealed a large cystic lesion involving the C1 lamina and right lateral
mass. The patient underwent ION-assisted aggressive intralesional resection of
the ABC and reconstruction of the C1 lateral mass with a static titanium cage,
supplemented with posterior fusion from the occiput to C3. At 2-year follow-up,
there was no evidence of recurrence and the hardware remained intact.
CONCLUSIONS: ION is a useful aid in assessing the extent of tumor resection and
performing cage reconstruction of the C1 lateral mass.
PMID- 28408259
TI - Pediatric Basal Ganglia Region Tumors: Clinical and Radiologic Features
Correlated with Histopathologic Findings.
AB - PURPOSE: To summarize the clinical and radiologic features of pediatric basal
ganglia region tumors (PBGRT) in correlation with their histopathologic findings
to reduce inappropriate surgery and identify tumors that can benefit from maximal
safe resection. METHODS: The records of 35 children with PBGRT treated in our
hospital from December 2011 to December 2015 were analyzed retrospectively. The
clinical and radiologic features of these tumors were summarized and correlated
with their histopathologic diagnosis. RESULTS: Our series included 15
astrocytomas and 11 germ cell tumors (GCTs). Basal ganglia astrocytomas were
characterized by various clinical presentations and an ill-circumscribed mass
with the involvement of surrounding structures on neuroimaging and mostly
occurred in the first decade of life (n = 10; 66.7%). Basal ganglia GCT mostly
occurred in the second decade of life (n = 8; 72.7%) with hemiparesis as the most
common symptom (n = 9; 81.8%). The tumors were located predominantly in the caput
of caudate nucleus (n = 8; 72.7%) with hemiatrophy as the typical sign (n = 8;
72.7%). Occasionally, other tumors also could occur in this region, including
primitive neuroectodermal tumor (n = 1), atypical teratoid/rhabdoid tumor (n =
1), anaplastic ependymoma (n = 1), lymphoma (n = 1), extraventricular neurocytoma
(n = 1), gangliogliomas (n = 2), oligodendroglioma (n = 1), and dysembryoplastic
neuroepithelial tumor (n = 1). CONCLUSIONS: Astrocytoma and GCT are the most
common PBGRTs. Low-grade astrocytomas could benefit from maximal surgical
resection, whereas GCTs merit neoadjuvant chemoradiation therapy followed by
second-look surgery. We advocate routine testing of tumor markers and analysis of
their clinical and radiologic features to optimize the therapeutic strategy.
PMID- 28408262
TI - Optimization of Microelectrode Recording in Deep Brain Stimulation Surgery Using
Intraoperative Computed Tomography.
AB - BACKGROUND: Microelectrode recording (MER) is used to confirm targeting accuracy
during deep brain stimulation (DBS) surgery. We describe a technique using
intraoperative computed tomography (CT) extrapolation (iCTE) to predetermine and
adjust the trajectory of the guide tube to improve microelectrode targeting
accuracy. We hypothesized that this technique would decrease the number of MER
tracks and operative time, while increasing the recorded length of the
subthalamic nucleus (STN). METHODS: Thirty-nine patients with Parkinson's disease
who underwent STN DBS before the iCTE method were compared with 33 patients
undergoing STN DBS using iCTE. Before dural opening, a guide tube was inserted
and rested on dura. Intraoperative computed tomography (iCT) was performed, and a
trajectory was created along the guide tube and extrapolated to the target using
targeting software. If necessary, headstage adjustments were made to correct for
error. The guide tube was inserted, and MER was performed. iCT was performed with
the microelectrode tip at the target. Coordinates were compared with
planned/adjusted track coordinates. Radial error between the MER track and the
planned/adjusted track was calculated. Cases before and after implementation of
iCTE were compared to determine the impact of iCTE on operative time, number of
MER tracks and recorded STN length. RESULTS: The use of iCTE reduced the average
radial MER track error from 1.90 +/- 0.12 mm (n = 54) to 0.84 +/- 0.09 mm (n =
49) (P < 0.001) while reducing the operative time for bilateral lead placement
from 272 +/- 9 minutes (n = 30) to 233 +/- 10 minutes (n = 24) (P < 0.001). The
average MER tracks per hemisphere was reduced from 2.24 +/- 0.13 mm (n = 66) to
1.75 +/- 0.09 mm (n = 63) (P < 0.001), whereas the percentage of hemispheres
requiring a single MER track for localization increased from 29% (n = 66) to 43%
(n = 63). The average length of recorded STN increased from 4.01 +/- 0.3 mm (n =
64) to 4.75 +/- 0.28 mm (n = 56) (P < 0.05). CONCLUSION: iCTE improves
microelectrode accuracy and increases the first-pass recorded length of STN,
while reducing operative time. Further studies are needed to determine whether
this technique leads to less morbidity and improved clinical outcomes.
PMID- 28408263
TI - Volumetric Analysis of Extent of Resection, Survival, and Surgical Outcomes for
Insular Gliomas.
AB - BACKGROUND: Insular gliomas are challenging tumors to surgically resect owing to
the anatomy surrounding them. This study evaluates the role of extent of
resection (EOR) and molecular markers in surgical outcome and survival for
insular gliomas. METHODS: Seventy-four patients who had undergone initial
resection for insular glioma by the same surgeon between 2006 and 2016 were
analyzed. Low-grade gliomas (LGGs) (grade II) and high-grade gliomas (HGGs)
(grade III/IV) were analyzed for the prognostic role of volumetric EOR and
molecular markers in patient survival outcomes. RESULTS: The cohort included 25
patients with LGGs (33.8%) and 49 patients with HGGs (66.2%). Median EOR was
91.7% (range, 10%-100%). New permanent postoperative deficits were found in 2.7%
of patients. Patients with LGGs with >=90% EOR had 5-year survival of 100%, and
patients with <90% EOR had 5-year survival of 80%. Patients with HGGs with >=90%
EOR had 2-year survival of 83.7%, and patients with <90% EOR had 2-year survival
of 43.8%. For LGGs, EOR was predictive of overall survival (P = 0.017),
progression-free survival (PFS) (P = 0.039), and malignant PFS (P = 0.014),
whereas 1p/19q codeletion was predictive of PFS (P = 0.014). For HGGs, EOR was
predictive of overall survival (P = 0.020) and PFS (P = 0.024). Preoperative
tumor volume most significantly affected EOR for insular gliomas (R2 = 0.053, P =
0.048). CONCLUSIONS: Extensive resections of insular gliomas can be achieved with
low morbidity and can improve overall survival and PFS. In this series of LGGs,
EOR was associated with longer malignant PFS, and 1p/19q codeletion was
predictive of PFS.
PMID- 28408264
TI - Single-Session Hematoma Removal and Transcranial Coil Embolization for a
Cavernous Sinus Dural Arteriovenous Fistula: A Technical Case Report.
AB - BACKGROUND: Patients with cavernous sinus dural arteriovenous fistulas (CS dAVFs)
with cortical venous varix are indicated for aggressive treatment because of the
associated risk for intracranial hemorrhage. CASE DESCRIPTION: We present a case
of surgical transvenous embolization in an 84-year-old woman with CS dAVF who
presented with massive intracerebral hematoma. Cerebral angiograms revealed the
dural AVF drained only into the superficial middle cerebral vein. Because an
emergent mass reduction and prevention of rebleeding were necessary, single
session hematoma removal and transcranial embolization of a CS dAVF were
performed in the neurosurgical operating room, using a mobile C-arm fluoroscopy.
After the right frontotemporal craniotomy, intracerebral hematoma was removed and
coil packing of the affected cavernous sinus was successfully performed via the
dilated superficial middle cerebral vein. CONCLUSION: The transcortical vein
approach enables occlusion of CS dAVF with isolated cortical venous drainage and
may be a valuable alternative approach for some cases needed emergency
craniotomy.
PMID- 28408265
TI - Spine Surgery Outcomes in Elderly Patients Versus General Adult Patients in the
United States: A MarketScan Analysis.
AB - OBJECTIVE: To compare spine surgery outcomes in elderly patients (80-103 years
old) versus general adult patients (18-79 years-old) in the United States.
METHODS: Truven Health Analytics MarketScan Research Databases (2000-2012) were
queried. Patients with a diagnosis of degenerative disease of the spine without
concurrent spinal stenosis, spinal stenosis without concurrent degenerative
disease, or degenerative disease with concurrent spinal stenosis and who had
undergone decompression without fusion, fusion without decompression, or
decompression with fusion procedures were included. Indirect outcome measures
included length of stay, in-hospital mortality, in-hospital and 30-day
complications, and discharge disposition. RESULTS: Patients (N = 155,720) were
divided into elderly (n = 10,232; 6.57%) and general adult (n = 145,488; 93.4%)
populations. Mean length of stay was longer in elderly patients versus general
adult patients (3.62 days vs. 3.11 days; P < 0.0001). In-hospital mortality was
more common in elderly patients versus general adult patients (0.31% vs. 0.06%; P
< 0.0001). In-hospital and 30-day complications were more common in elderly
patients versus general adult patients (11.3% vs. 7.15% and 17.8% vs. 12.6%; P <
0.0001). Nonroutine discharge was more common in elderly patients versus general
adult patients (33.7% vs. 16.2%; P < 0.0001). CONCLUSIONS: Our results revealed
significantly longer hospital stays, more in-hospital mortalities, and more in
hospital and 30-day complications after decompression without fusion, fusion
without decompression, or decompression with fusion procedures in elderly
patients.
PMID- 28408266
TI - Analysis of Clinical Results of Three Different Routes of Percutaneous Endoscopic
Transforaminal Lumbar Discectomy for Lumbar Herniated Disk.
AB - OBJECTIVE: Percutaneous endoscopic transforaminal lumbar discectomy (PETLD) can
be performed by using foraminal, intervertebral, and suprapedicular routes. The
aim of this study was to assess clinical results of three different routes of
PETLD. METHODS: One hundred eleven patients who underwent PETLD between January
2016 and October 2016 were included in this study. PETLD was performed using the
foraminal (group A), intervertebral (group B), and suprapedicular (group C)
routes in 32, 46, and 33 patients, respectively. Outcomes were evaluated using
the visual analogue scale (VAS), Oswestry Disability Index (ODI), and MacNab
criteria. RESULTS: Seventy-one men and 40 were women (mean age 53.33 +/- 14.12
years). The mean follow-up period was 6.44 +/- 3.26 months. The preoperative VAS
score decreased significantly (P < 0.01) in all 3 groups, but the postoperative
VAS score was higher for the foraminal route than for the intervertebral (P =
0.001) and suprapedicular routes (P < 0.001). Excellent outcome grade according
to MacNab criteria was less in foraminal route (18.7%) than in intervertebral
(52.2%) and suprapedicular (56.7%) routes. ODI improved significantly (P < 0.01)
in all 3 groups. CONCLUSION: All 3 routes of PETLD resulted in good to excellent
clinical results. Nevertheless, the postoperative VAS score was higher for the
foraminal route than for the intervertebral and suprapedicular routes, probably
not because of the surgery but because of the neurologic characteristics of the
disk location. The surgeon should consider this problem to alleviate pain
postoperatively and counsel to patient well before surgery.
PMID- 28408267
TI - Population pharmacokinetics of moxifloxacin, cycloserine, p-aminosalicylic acid
and kanamycin for the treatment of multi-drug-resistant tuberculosis.
AB - Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive,
supervised chemotherapy because second-line anti-TB drugs have a narrower
therapeutic range than first-line drugs. This study aimed to develop population
pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB,
evaluate the recommended dosage regimens and, if necessary, suggest new dosage
regimens. A prospective, single-centre PK study was performed on second-line anti
TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic
acid (PAS), kanamycin and other second-line drugs were administered to the
patients. Plasma concentrations were analysed using ultra-performance liquid
chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were
developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON
Development Solutions, Ellicott City, MD, USA). Simulations were performed using
the calculated PK parameters. The respective absorption rate constant, apparent
clearance and apparent volume of distribution values were as follows: 0.305/h,
9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for
cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2
L for kanamycin. The simulations showed that the following dosage regimens were
more likely to be within the recommended concentration ranges than the raw data
in this study: 200 mg of moxifloxacin once daily (QD) (patient weight <50 kg) and
400 mg of moxifloxacin QD (patient weight >=50 kg), 500-750 mg of cycloserine QD,
4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD.
These findings indicate that the recommended doses should be revised to improve
the clinical outcomes of MDR-TB treatment.
PMID- 28408268
TI - Chemical constituents from the whole plants of Pilea cavaleriei Levl subsp.
cavaleriei.
AB - Three new sesquiterpene glycosides (1-3), three new glycerol glycosides (4-6),
two new alkaloids (7-8), together with seven known compounds (9-15) all of which
were isolated from the genus Pilea for the first time, were isolated from the
whole plants of Pilea cavaleriei Levl subsp. cavaleriei. Their structures were
determined by extensive spectroscopic techniques and chemical methods. The
cytotoxic activity of the isolated compounds was evaluated against four cancer
cell lines, and none of the tested compounds caused a significant reduction of
the cell number.
PMID- 28408269
TI - Chlorajaponols A-F, sesquiterpenoids from Chloranthus japonicus and their in
vitro anti-inflammatory and anti-tumor activities.
AB - Two new eudesmane sesquiterpenoids, chlorajaponols A-B (1-2), two new guaiane
sesquiterpenoids, chlorajaponols C-D (3-4), a new germacrane sesquiterpenoid,
chlorajaponol E (5), and a new lindenane sesquiterpenoid, chlorajaponol F (6),
along with 8 known sesquiterpenoids and 6 known disesquiterpenoids, were isolated
from the whole plant of Chloranthus japonicus. Their structures were established
by extensive analysis of NMR spectroscopic data in combination with mass
spectrometry. The structures of compounds 1-4 were confirmed by single crystal X
ray diffraction (CuKalpha radiation). The possible biogenetic pathways of
compounds 1-6 were discussed. Chlorajaponol B (2) showed significant inhibition
against nitric oxide (NO) release in LPS-induced RAW264.7 macrophages with the
IC50 value of 9.56+/-0.71MUM, comparable to that of positive control amino
guanidine (8.50+/-0.35MUM). Shizukaol C (18) strongly suppressed the
proliferation of three human tumor cell lines MGC803, HepG2, and HL-60 with IC50
values of 4.60+/-1.05MUM, 3.17+/-0.66MUM, and 1.57+/-0.27MUM, respectively.
PMID- 28408271
TI - Quid pro Quo: A Tumor is Not Alone.
PMID- 28408270
TI - Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and
GtfB deletion on PsrP-associated virulence properties.
AB - Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates
Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37
kbp pathogenicity island encoding PsrP and its accessory genes. PCR amplification
of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three
operons: psrP-glyA, glyB, and glyC-asp5. Transcription of all three operons was
greatest during biofilm growth and immunoblot analyses confirmed increased PsrP
production by biofilm pneumococci. Using gas chromatography-mass spectrometry we
identified monomeric N-acetylglucosamine as the primary glycoconjugate present on
a recombinant intracellular version of PsrP, i.e. PsrP1-734. This finding was
validated by immunoblot using lectins with known carbohydrate specificities. We
subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for
addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated
virulence properties. These deletions negatively affected our ability to detect
PsrP1-734 in bacterial whole cell lysates. Moreover, S. pneumoniae mutants
lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm
formation, adhesion to lung epithelial cells, and pneumonia in mice. Our studies
identify the transcriptional organization of psrP-secY2A2 and show the
indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
PMID- 28408272
TI - Successful management of a neck hematoma following simulation training.
PMID- 28408273
TI - Preventing medication errors in anesthesia and critical care (abbreviated
version).
AB - Drug medication errors remain a major safety issue in anaesthesia and intensive
care, and prevention measures need to be strengthened. This is why the French
Society of Anaesthesia and Intensive Care and the French Society of Clinical
Pharmacy have profoundly reviewed their previous recommendations published in
2007. The 2017 recommendations are based on the literature but also on feedback
from field professionals targeting patient safety. They share many similarities
with recommendations issued from other countries (European countries, North
America and Australia in particular) on this subject. Specific measures to
prevent preparation, reconstitution and administration errors are detailed.
Medical products using small bore connectors specified in the ISO 80369 series
allow the prevention of administrtion errors. Specific labeling should be used
according to an international color-coding of syringes, routes of administration,
preparation bags, PCAs and PCEAs, trolleys or drug storage devices. A risk
mapping must be established a priori and medication errors reporting is
imperative in order to analyze them a posteriori in departmental meetings
(REMED). Self-assessment, or external assessment, must be conducted. All of the
proposed recommendations reinforce the culture of safety, which is essential to
the practice of anaesthesia and intensive care.
PMID- 28408274
TI - Bifidobacterium longum vertebrodiscitis in a patient with cirrhosis and prostate
cancer.
AB - Bifidobacterium species are anaerobic, Gram-positive bacilli that colonize the
human intestinal tract and oral cavity. They are an infrequent cause of invasive
human infection. We report a case of Bifidobacterium longum lumbar
vertebrodiscitis in a 71 year old man who was subsequently diagnosed with liver
cirrhosis and prostate cancer. The clinical outcome was good following antibiotic
treatment with penicillin and clindamycin. The laboratory identification of
Bifidobacterium species and risk factors for invasive infection are discussed.
PMID- 28408275
TI - Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A
systematic literature review and meta-analysis of randomized controlled trials
versus placebo.
AB - OBJECTIVES: Complex Regional Pain Syndrome Type 1 is a severely disabling pain
syndrome with no definite established treatment. We have performed a systematic
literature review and meta-analysis of all randomized controlled trials to assess
the benefit of bisphosphonates on pain and function in patients with Complex
Regional Pain Syndrome Type 1. METHODS: A systematic literature search was
performed in the Medline, Embase and Cochrane databases. Two authors selected
independently blinded randomized trials comparing bisphosphonates to placebo on
short-term (J30 to J40) and medium term pain (M2-M3), safety and function in
patients with CRPS 1. The methodological quality of the studies was analyzed.
Data were aggregated using the method of the inverse of the variance. RESULTS:
258 articles were identified. Four trials of moderate to good quality comprising
181 patients (90 in the bisphosphonate group and 91 in the placebo group) were
included in this meta-analysis. Short-term pain Visual Analog Scale was
significantly lower in the bisphosphonate group versus the placebo group (SMD=
2.6, 95%CI [-1.8, -3.4], P<0.001), as well as the medium term Visual Analog Scale
pain (SMD=-2.5, 95%CI [-1.4, -3.6], P<0.001). There were more adverse events in
the bisphosphonate group (35.5%) than in the placebo group (16.4%) with a
relative risk of 2.1 (95%CI [1.3, 3.5], P=0.004) and a number needed to harm of
4.6, (95%CI [2.4, 168.0]) but no serious side effects. CONCLUSIONS: Our results
suggest that bisphosphonates reduce pain in patients with Complex Regional Pain
Syndrome type 1. Other studies are needed to determine their effectiveness.
PMID- 28408276
TI - Low serum concentrations of Irisin are associated with increased risk of hip
fracture in Chinese older women.
AB - OBJECTIVE: Irisin derived from muscle in response to exercise may be the
molecular entity responsible for muscle wasting-osteoporosis connectivity in the
elderly. The objective of the study was to determine whether serum Irisin
(sIrisin) provides information on hip fracture prediction which were independent
of bone mineral density (BMD) and the fracture risk assessment tool (FRAX)
algorithm. METHODS: This study enrolled 160 older women (ages, 70-90y) with
minimal trauma hip fractures (MTHFs) and 160 age-matched women without fracture
serving as controls. Clinical features, BMD and bone turnover markers including
sIrisin levels were measured after fracture within 2 days as baseline. RESULTS:
sIrisin levels were significantly lower (361.5+/-140.0ng/mL vs 478.5+/
159.6ng/mL, P<0.001) in cases than controls. After multivariate analysis, sIrisin
remained as an independent variable of BMD, which explained 17.8% of femoral neck
BMD and 22.5% of lumbar spine BMD, respectively. The odds ratio (OR) of MTHFs
comparing the lowest (<320.1ng/mL) to highest (>524.5ng/mL) quartiles was 1.95
(95% CI 1.23-3.79, P<0.05) for sIrisin. Adjustment for age, body mass index, time
since menopause and exercise >=30min/day yielded similar results, and BMD of
femoral neck also did not change these associations. Taking FRAX score into
account attenuated the association somewhat: OR of hip fracture was 1.81 (95% CI
1.26-3.49, P<0.05) in first versus fourth quartile of sIrisin. There was a
negative gradient of risk by decreasing quartile in sIrisin. CONCLUSIONS: Low
concentrations of sIrisin in older women were independently associated with
increased risk of hip fractures when adjusted for BMD or FRAX score.
PMID- 28408277
TI - Lung transplantation in systemic sclerosis: A single center cohort study.
AB - OBJECTIVE: Lung transplantation (LT) has been proposed as a treatment for
advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH)
associated to systemic sclerosis (SSc) but few studies have been reported. The
aim of this study was to describe the clinical features, complications and
survival of a single-center cohort of patients with SSc that underwent LT and to
compare their survival with a group of non-SSc transplanted patients. METHODS:
Fifteen patients with SSc were transplanted between May 2005 and April 2015.
Standard international criteria were used to determine eligibility for LT. The
severity of gastroesophageal involvement was not considered as a major
contraindication if symptoms were under control. RESULTS: Eight (53.3%) patients
had diffuse cutaneous SSc. Eleven (73%) underwent bilateral LT. The main
indication for LT was ILD, with or associated PH in 4 cases. Acute cellular
rejection and infections were the most frequent complications. Functional lung
tests tended to keep stable after transplantation. Median survival was 2.4 years
(Q1-Q3: 0.7-3.7 years). We did not find differences in survival between patients
transplanted with SSc versus those transplanted due to non-SSc ILD or PH. SSc
complications were scarce with no patient developing PH after LT. CONCLUSIONS: LT
was an effective treatment for advanced ILD and/or PH associated to SSc in our
study. Gastroesophageal reflux was not a limitation for LT in SSc in this study.
Complications and survival did not differ from non-SSc patients undergoing LT.
PMID- 28408278
TI - Study on the chemical and microbial composition and probiotic characteristics of
dominant lactic acid bacteria in fermented poultry slaughterhouse waste.
AB - This study aimed to evaluate the quality of fermented poultry slaughterhouse
waste and isolate and identify the probiotic bacteria present in it. Poultry
slaughterhouse waste samples supplemented with 5% starter culture and 0.2%
propionic acid received one of four experimental treatments, which consisted of
further supplementation with: (1) 10% molasses (M10); (2) 15% molasses (M15); (3)
10% molasses with 200ppm butylated hydroxytoluene (MB10); and (4) 15% molasses
with 200ppm butylated hydroxytoluene (MB15). All experimental treatments
(silages) were fermented for 6days with sampling before fermentation (day 1) and
at the end of days 3 and 6. The pH of the silages decreased during the
fermentation as it was lower on days 3 and 6 than day 1 (P<0.05). On day 6 of the
experiment, the number of lactic acid bacteria in MB15 was significantly (P<0.05)
higher than in MB10. The percentage of non-protein nitrogen increased (P<0.05) on
days 3 and 6 of fermentation. The amount of malondialdehyde indicated that the
peroxidation ratio decreased (P<0.05) with increasing the fermentation time.
Among the 23 lactic acid bacteria detected in MB15, nine isolates (39.1%)
belonged to the species Lactobacillus plantarum, ten (43.5%) belonged to the
species Lactobacillus rhamnosus, and four (43.5%) belonged to the species
Lactobacillus fermentum. The isolates LPL9, LRH25, and LFE26 were identified as
the strain of L. plantarum, L. ramnosus, and L. fermentum, respectively, that
demonstrated the best characteristics for use as a probiotic. The results of this
experiment indicated that the fermentation is an advisable method for reusing the
nutrients of poultry slaughterhouse waste and producing a probiotic supplement.
PMID- 28408279
TI - Evaluation of leachate dissolved organic nitrogen discharge effect on wastewater
effluent quality.
AB - Nitrogen is limited more and more frequently in wastewater treatment plant (WWTP)
effluents because of the concern of causing eutrophication in discharge waters.
Twelve leachates from eight landfills in Florida and California were
characterized for total nitrogen (TN) and dissolved organic nitrogen (DON). The
average concentration of TN and DON in leachate was approximately 1146mg/L and
40mg/L, respectively. Solid-phase extraction was used to fractionate the DON
based on hydrophobic (recalcitrant fraction) and hydrophilic (bioavailable
fraction) chemical properties. The average leachate concentrations of
bioavailable (bDON) and recalcitrant (rDON) DON were 16.5mg/L and 18.4mg/L,
respectively. The rDON fraction was positively correlated, but with a low R2,
with total leachate apparent color dissolved UV254, chemical oxygen demand (COD),
and humic acid (R2 equals 0.38, 0.49, and 0.40, respectively). The hydrophobic
fraction of DON (rDON) was highly colored. This fraction was also associated with
over 60% of the total leachate COD. Multiple leachate and wastewater co-treatment
simulations were carried out to assess the effects of leachate on total nitrogen
wastewater effluent quality using removals for four WWTPs under different
scenarios. The calculated pass through of DON suggests that leachate could
contribute to significant amounts of nitrogen discharged to aquatic systems.
PMID- 28408280
TI - Status and perspectives of municipal solid waste incineration in China: A
comparison with developed regions.
AB - With the rapid expansion of municipal solid waste (MSW) incineration, the
applicability, technical status, and future improvement of MSW incineration
attract much attention in China. This paper aims to be a sensible response, with
the aid of a comparison between China and some representative developed regions
including the EU, the U.S., Japan, South Korea, and Taiwan area. A large number
of up-to-date data and information are collected to quantitatively and
impartially support the comparison, which covers a wider range of key points
including spatial distribution, temporal evolution, technologies, emissions, and
perspectives. Analysis results show that MSW incineration is not an outdated
choice; however, policy making should prevent the potentially insufficient
utilization of MSW incinerators. The structure of MSW incineration technologies
is changing in China. The ratio of plants using fluidized bed is decreasing due
to various realistic reasons. Decision-makers would select suitable combustion
technologies by comprehensive assessments, rather than just by costs. Air
pollution control systems are improved with the implementation of China's new
emission standard. However, MSW incineration in China is currently blamed for
substandard emissions. The reasons include the particular elemental compositions
of Chinese MSW, the lack of operating experience, deficient fund for compliance
with the emission standard, and the lack of reliable supervisory measures. Some
perspectives and suggestions from both technical and managerial aspects are given
for the compliance with the emission standard. This paper can provide strategic
enlightenments for MSW management in China and other developing countries.
PMID- 28408281
TI - Comparison of ANN (MLP), ANFIS, SVM, and RF models for the online classification
of heating value of burning municipal solid waste in circulating fluidized bed
incinerators.
AB - The heating values, particularly lower heating values of burning municipal solid
waste are critically important parameters in operating circulating fluidized bed
incineration systems. However, the heating values change widely and frequently,
while there is no reliable real-time instrument to measure heating values in the
process of incinerating municipal solid waste. A rapid, cost-effective, and
comparative methodology was proposed to evaluate the heating values of burning
MSW online based on prior knowledge, expert experience, and data-mining
techniques. First, selecting the input variables of the model by analyzing the
operational mechanism of circulating fluidized bed incinerators, and the
corresponding heating value was classified into one of nine fuzzy expressions
according to expert advice. Development of prediction models by employing four
different nonlinear models was undertaken, including a multilayer perceptron
neural network, a support vector machine, an adaptive neuro-fuzzy inference
system, and a random forest; a series of optimization schemes were implemented
simultaneously in order to improve the performance of each model. Finally, a
comprehensive comparison study was carried out to evaluate the performance of the
models. Results indicate that the adaptive neuro-fuzzy inference system model
outperforms the other three models, with the random forest model performing
second-best, and the multilayer perceptron model performing at the worst level. A
model with sufficient accuracy would contribute adequately to the control of
circulating fluidized bed incinerator operation and provide reliable heating
value signals for an automatic combustion control system.
PMID- 28408282
TI - An overview of the 2017 ILAE operational classification of seizure types.
PMID- 28408283
TI - Computer-naive health workers can use a tablet-based epilepsy diagnosis app.
PMID- 28408284
TI - Conversion from weight to volume of mastectomy specimen: Convenient equations.
AB - Accurate restoration of the volume lost during breast removal is the key to
achieve beautiful, symmetric breasts. This study aimed to devise a simpler and
more accurate method for measuring breast tissue volume by studying the
relationship between weight and volume of the excised tissue according to
density. Mammograms of 276 women who were advised to undergo breast
reconstruction surgery were divided into 4 different groups according to tissue
densities. The correlation between weight and volume was studied for each group.
The regression equations are as follows: 1st group: V = 1.218 * W+7.45 (V:
volume, W: weight). 2nd group: V = 1.036 * W + 10.36. 3rd group: V = 0.969 * W
7.47. 4th group: V = 0.871 * W-14.13. These equations will be useful for
reconstruction of natural-appearing and symmetric breasts following mastectomy.
PMID- 28408285
TI - From epigenetic landscape to phenotypic fitness landscape: Evolutionary effect of
pathogens on host traits.
AB - The epigenetic landscape illustrates how cells differentiate through the control
of gene regulatory networks. Numerous studies have investigated epigenetic gene
regulation but there are limited studies on how the epigenetic landscape and the
presence of pathogens influence the evolution of host traits. Here, we formulate
a multistable decision-switch model involving several phenotypes with the
antagonistic influence of parasitism. As expected, pathogens can drive dominant
(common) phenotypes to become inferior through negative frequency-dependent
selection. Furthermore, novel predictions of our model show that parasitism can
steer the dynamics of phenotype specification from multistable equilibrium
convergence to oscillations. This oscillatory behavior could explain pathogen
mediated epimutations and excessive phenotypic plasticity. The Red Queen dynamics
also occur in certain parameter space of the model, which demonstrates winnerless
cyclic phenotype-switching in hosts and in pathogens. The results of our
simulations elucidate the association between the epigenetic and phenotypic
fitness landscapes and how parasitism facilitates non-genetic phenotypic
diversity.
PMID- 28408286
TI - Carcinogenicity of welding, molybdenum trioxide, and indium tin oxide.
PMID- 28408287
TI - The Reluctant Cardiac Patient.
PMID- 28408288
TI - Joe's Decision.
PMID- 28408289
TI - Dopaminergic control of anxiety in young and aged zebrafish.
AB - Changes in the expression of the dopamine transporter (DAT), or the sensitivity
of dopamine receptors, are associated with aging and substance abuse and may
underlie some of the symptoms common to both conditions. In this study, we
explored the role of the dopaminergic system in the anxiogenic effects of aging
and acute cocaine exposure by comparing the behavioral phenotypes of wild type
(WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the
involvement of specific dopamine receptors in anxiety states, antagonists to D1
(SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO
results in a chronic anxiety-like state, seen as an increase in bottom-dwelling
and thigmotaxis. Similar effects were produced by aging and acute cocaine
administration, both leading to reduction in DAT mRNA abundance (qPCR).
Inhibition of D1 activity counteracted the anxiety-like effects associated with
DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced
anxiety in young DAT-KO, and enhanced the anxiogenic effects of cocaine in WT,
but did not affect aged WT or DAT-KO fish. These findings provide new evidence
that the dopaminergic system plays a critical role in anxiety-like states, and
suggest that adult zebrafish provide a sensitive diurnal vertebrate model for
elucidating the molecular mechanisms of anxiety and a platform for anxiolytic
drug screens.
PMID- 28408290
TI - Automated template-based brain localization and extraction for fetal brain MRI
reconstruction.
AB - Most fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant
voxels of low-resolution (LR) images to enhance the quality of inter-slice motion
correction and image reconstruction. Consequently the fetal brain needs to be
localized and extracted as a first step, which is usually a laborious and time
consuming manual or semi-automatic task. We have proposed in this work to use age
matched template images as prior knowledge to automatize brain localization and
extraction. This has been achieved through a novel automatic brain localization
and extraction method based on robust template-to-slice block matching and
deformable slice-to-template registration. Our template-based approach has also
enabled the reconstruction of fetal brain images in standard radiological
anatomical planes in a common coordinate space. We have integrated this approach
into our new reconstruction pipeline that involves intensity normalization, inter
slice motion correction, and super-resolution (SR) reconstruction. To this end we
have adopted a novel approach based on projection of every slice of the LR brain
masks into the template space using a fusion strategy. This has enabled the
refinement of brain masks in the LR images at each motion correction iteration.
The overall brain localization and extraction algorithm has shown to produce
brain masks that are very close to manually drawn brain masks, showing an average
Dice overlap measure of 94.5%. We have also demonstrated that adopting a slice-to
template registration and propagation of the brain mask slice-by-slice leads to a
significant improvement in brain extraction performance compared to global rigid
brain extraction and consequently in the quality of the final reconstructed
images. Ratings performed by two expert observers show that the proposed pipeline
can achieve similar reconstruction quality to reference reconstruction based on
manual slice-by-slice brain extraction. The proposed brain mask refinement and
reconstruction method has shown to provide promising results in automatic fetal
brain MRI segmentation and volumetry in 26 fetuses with gestational age range of
23 to 38 weeks.
PMID- 28408292
TI - Threat distractor and perceptual load modulate test-retest reliability of
anterior cingulate cortex response.
AB - Accumulating data from fMRI studies implicate the rostral anterior cingulate
cortex (rACC) in inhibition of attention to threat distractors that compete with
task-relevant goals for processing resources. However, little data is available
on the reliability of rACC activation. Our aim in the current study was to
examine test-retest reliability of rACC activation over a 12-week period, in the
context of a validated emotional interference paradigm that varied in perceptual
load. During functional MRI, 23 healthy volunteers completed a task involving a
target letter in a string of identical letters (low load) or in a string of mixed
letters (high load) superimposed on angry, fearful, and neutral face distractors.
Intraclass correlation coefficients (ICCs) indicated that under low, but not high
perceptual load, rACC activation to fearful vs. neutral distractors was
moderately reliable. Conversely, regardless of perceptual load, rACC activation
to angry vs. neutral distractors was not reliable. Regarding behavioral
performance, ICCs indicated that accuracy was not reliable regardless of
distractor type or perceptual load. Although reaction time (RT) was similarly not
reliable regardless of distractor type under low perceptual load, RT to angry vs.
neutral distractors and to fearful vs. neutral distractors was reliable under
high perceptual load. Together, results indicate the test-retest reliability of
rACC activation and corresponding behavioral performance are context dependent;
reliability of the former varies as a function of distractor type and level of
cognitive demand, whereas reliability of the latter depends on behavioral index
(accuracy vs. RT) and level of cognitive demand but not distractor type.
PMID- 28408291
TI - Altered expression of circadian rhythm and extracellular matrix genes in the
medial prefrontal cortex of a valproic acid rat model of autism.
AB - Autism spectrum disorders (ASD) are a highly heterogeneous group of
neurodevelopmental disorders caused by complex interplay between various genes
and environmental factors during embryonic development. Changes at the molecular,
cellular and neuroanatomical levels are especially evident in the medial
prefrontal cortex (mPFC) of ASD patients and are particularly contributing to
social impairments. In the present study we tested the hypothesis that altered
neuronal development and plasticity, as seen in the mPFC of ASD individuals, may
result from aberrant expression of functionally connected genes. Towards this
end, we combined transcriptome sequencing and computational gene ontology
analysis to identify the molecular networks impaired in the mPFC of a valproic
acid (VPA) rat model of autism. This investigation identified two subsets of
genes differentially expressed in the mPFC of VPA rats: one group of genes being
functionally involved in the regulation of the circadian rhythm, while the second
group encompasses a set of differentially expressed collagen genes acting within
the extracellular matrix. Ultimately, our integrated transcriptome analysis
identified a distinct subset of altered gene networks in the mPFC of VPA rats,
contributing to our understanding of autism at the molecular level, thus
providing novel insight into the genetic alterations associated with this
neurodevelopmental disorder.
PMID- 28408293
TI - Vesicular monoamine transporter 1 gene polymorphism and white matter integrity in
major depressive disorder.
AB - The genetic variant of the vesicular monoamine transporter 1 gene (VMAT1) has
been suggested to be associated with monoaminergic signaling and neural circuit
activity related to emotion processing. We aimed to investigate microstructural
changes in white matter tracts of patients with major depressive disorder (MDD),
and examined the interaction effect between VMAT1 Thr136Ile (rs1390938)
polymorphism and MDD on white matter integrity. Diffusion tensor imaging (DTI)
and VMAT1 Thr136Ile (rs1390938) genotyping were performed on 103 patients
diagnosed with MDD and 83 healthy control participants. DTI was used to
investigate microstructural changes in white matter tracts in patients compared
to healthy controls. The possible interaction effect between rs1390938 and MDD on
white matter integrity was also assessed. Patients with MDD exhibited lower
fractional anisotropy (FA) values of the forceps major (p<0.001), forceps minor
(p=0.001), inferior longitudinal fasciculus (left: p=0.001; right: p<0.001),
parietal endings of the superior longitudinal fasciculus (left: p<0.001; right:
p=0.002), left temporal endings of the superior longitudinal fasciculus
(p=0.001), and right uncinate fasciculus (p=0.001). Significant genotype-by
diagnosis interaction effects were observed on FA values of the right uncinate
fasciculus (p=0.001), with A-allele carrier patients exhibiting lower FA values
compared to G-allele homozygous patients (p=0.003). No significant differences in
FA values were observed between genotype subgroups among healthy controls. Our
results may contribute to the evidence indicating an association between the
VMAT1 gene and structural brain alterations in depression.
PMID- 28408294
TI - Resilience and cross-network connectivity: A neural model for post-trauma
survival.
AB - Literature on the neurobiological bases of Post-Traumatic Stress Disorder (PTSD)
considers medial Prefrontal cortex (mPFC), a core region of the Default Mode
Network (DMN), as a region involved in response regulation to stressors.
Disrupted functioning of the DMN has been recognized at the basis of the
pathophysiology of a number of mental disorders. Furthermore, in the evaluation
of the protective factors to trauma consequence, an important role has been
assigned to resilience. Our aim was to investigate the specific relation of
resilience and PTSD symptoms severity with resting state brain connectivity in a
traumatized population using magnetoencephalography (MEG), a non-invasive imaging
technique with high temporal resolution and documented advantages in clinical
applications. Nineteen Trauma Exposed non-PTSD (TENP) and 19 PTSD patients
participated to a resting state MEG session. MEG functional connectivity of mPFC
seed to the whole brain was calculated. Correlation between mPFC functional
connectivity and Clinician Administered PTSD Scale (CAPS) or Connor-Davidson
Resilience Scale (CD-RISC) total score was also assessed. In the whole group, it
has been evidenced that the higher was the resilience, the lower was the cross
network connectivity between DMN and Salience Network (SN) nodes. Contrarily, in
the TENP group, the negative correlation between resilience and DMN-SN cross
interaction disappeared, suggesting a protective role of resilience for brain
functioning. Regarding our findings as a continuum between healthy and
pathological after trauma outcomes, we could suggest a link between resilience
and the good dialogue between the networks needed to face a traumatic event and
its long-term consequence on individuals' lives.
PMID- 28408297
TI - Time-source of neural plasticity in complex bimanual coordinative tasks:
Juggling.
AB - Brain plasticity is especially stimulated by complex bimanual tasks, because, as
for juggling, they require simultaneous control of multiple movements, high level
of bimanual coordination, balance and sustained swapping attention to multiple
objects interacting with both hands. Neuroimaging studies on jugglers showed
changes in white and grey matter after juggling training, while the very few
electroencephalographic (EEG) studies showed changes in the frequency domain.
However, no study has focused on the fine temporal brain activations during a
bimanual coordinative task in ecological settings. We aimed at understanding the
neural correlates of juggling tasks comparing expert jugglers to non-jugglers.
Both groups performed two juggling tasks with increasing difficulty (1-ball
fountain and 2-ball shower in non-jugglers, 2- and 3-ball shower in expert
jugglers), while the EEG was recorded. This design allowed to compare brain
activities related to increasing task difficulty within the same group, and the
two groups on the same task. The movement-related cortical potentials (MRCPs) for
each task were segmented into epochs lasting 4.5s (-1.5/+3.0s). Results showed
enhanced prefrontal recruitment with increasing task difficulty in both groups,
even before movement onset. Comparing the groups on the same task, non-jugglers
showed enhanced activation of prefrontal regions before and during the task
execution, whereas jugglers showed enhanced activity in motor-related regions.
The results provide a clear indication of practice-induced brain efficiency
during the performance of complex bimanual coordinative skills.
PMID- 28408296
TI - Percutaneous radiofrequency ablation for renal cell carcinoma vs. partial
nephrectomy: Comparison of long-term oncologic outcomes in both clear cell and
non-clear cell of the most common subtype.
AB - OBJECTIVES: To compare the clinical outcomes of percutaneous radiofrequency
ablation (PRFA) and partial nephrectomy (PN) in patients with clear cell renal
cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC) of the most common
subtypes. MATERIALS AND METHODS: A retrospective study was conducted to review
the records of all the patients who underwent PRFA or PN between February 2005
and April 2014 at our institution. Patients with histologic confirmation of
ccRCC, papillary RCC, and chromophobe RCC were included. The Mann-Whitney U test
was applied to compare PRFA to PN in the ccRCC and nccRCC groups. The Kaplan
Meier method was used to generate the survival curves that were compared to the
log-rank test. RESULTS: A total of 264 patients meeting the selection criteria
were included in this study. The tumor size ranged from 0.9 to 7.0cm. The median
follow-up period was 78 months (range: 8-132 mo). Although PRFA provided
comparable 10-year overall survival rates and 10-year disease-free survival (DFS)
rates to PN both in ccRCC <=4cm and nccRCC, the 10-year DFS for patients treated
with PRFA was lower than that of PN in ccRCC >4cm. The DFS survival curve between
the 2 operations and 2 subtypes was statistically significant in patients with
tumor size >4cm. Limitations include retrospective review and selection bias.
CONCLUSIONS: Patients with T1b ccRCC treated with PRFA have less favorable
outcomes than those with PN whereas PRFA provides comparable oncologic outcomes
to PN in patients with T1b nccRCC. It is necessary to take RCC subtypes into
consideration when choosing a surgical approach to treat T1b RCC between PFRA and
PN.
PMID- 28408295
TI - Genomic alterations as predictors of survival among patients within a combined
cohort with clear cell renal cell carcinoma undergoing cytoreductive nephrectomy.
AB - PURPOSE: To establish prognostic genomic biomarkers for patients with metastatic
clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We identified 60
patients who presented with metastatic ccRCC at our institution between 2001 and
2015 and had genomic sequencing on their primary tumor. We pooled these patients
with 107 other patients with the same inclusion criteria from three well-known
public databases. Five commonly mutated genes were chosen for analysis: VHL,
PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the
Kaplan-Meier method and the log-rank test was used for comparisons between
groups. RESULTS: Median OS in the cohort was 2.5 years. Higher Fuhrman grade was
associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and
KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] =
0.58 [95% CI: 0.35-0.94] and HR = 0.43 [95% CI: 0.22-0.85], respectively). BAP1
mutations (P = 0.008) were associated with increased risk of death (HR = 1.81
[95% CI: 1.16-2.83]). There were significantly more female patients with a BAP1
mutation than females in the overall cohort (P = 0.001). CONCLUSIONS: Mutations
in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated
with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our
results expand upon efforts at understanding genomic biomarkers in localized
disease. Those efforts set the stage for our novel investigation examining
associations of select recurrent somatic mutations in stage IV patients with
ccRCC.
PMID- 28408298
TI - Antidepressant-like effect of valproic acid-Possible involvement of PI3K/Akt/mTOR
pathway.
AB - RATIONALE: Few studies suggest that antidepressants exert their effects by
activating some signaling pathways, including the phosphatidylinositol 3-kinase
(PI3K). Moreover, valproic acid (VPA) activates the PI3K pathway. Thus, here we
investigated the antidepressant-like effect of VPA and if its effect is related
to PI3K/Akt/mTOR activation. METHODS: C57Bl/6 (WT) and PI3Kgamma-/- mice received
VPA injections (30, 100 or 300mg/kg, i.p.) and 30min after they were submitted to
the forced swimming (FS), tail suspension (TS) and open field (OF) tests. Another
group was pretreated with rapamycin (5mg/kg, i.p.) 150min before VPA
administration. Akt phosphorylation levels were measured by Western blotting.
RESULTS: In WT mice, VPA (30mg/kg) reduced the immobility time in both FS and TS
tests. However, VPA (300mg/kg) increased the immobility time in FS test. All
doses of VPA did not alter locomotor activity. In PI3Kgamma-/- mice, none of the
doses revealed antidepressant-like effect. However, in the OF test, the lower
dose of VPA increased the travelled distance in comparison with vehicle group. An
increase in Akt phosphorylation levels was observed in WT, but not in PI3Kgamma-/
mice. Finally, the pretreatment of WT mice with rapamycin abolished the
antidepressant-like effect of VPA (30mg/kg) in FS test. CONCLUSION: These data
suggest that the antidepressant-like effects of VPA might depend on PI3K and mTOR
activation. Thus, more studies are necessary to investigate the mechanisms
involved in the antidepressant-like effect induced by VPA in order to investigate
novel therapeutic targets for the treatment of depression.
PMID- 28408300
TI - alpha9-nAChR knockout mice exhibit dysregulation of stress responses, affect and
reward-related behaviour.
AB - The alpha9alpha10-subtype of nicotinic acetylcholine receptor (nAChR) has
recently garnered interest in biomedicine and is being pursued as an analgesic
target. However, the receptor exhibits diverse tissue distribution, the function
of which is known to varying degrees, and targeting this receptor for clinical
treatments without a broad understanding of its function may have adverse
consequences. The alpha9alpha10-nAChR is expressed in the adrenal and pituitary
glands, suggesting a potential role in the stress response, but little is known
about its function in this tissue. Here we determined a role for the
alpha9alpha10-nAChR in behavioural and physiological stress responses, by
comparing the stress- and affect-related phenotypes of wildtype and alpha9-nAChR
knockout mice. Naive knockout mice exhibited largely normal behaviour on standard
tests of affective behaviour. However, after sub-chronic restraint stress
knockout mice showed significantly decreased stress-induced arousal and increased
anxiety-like behaviour when compared to wildtype animals. Physiologically,
corticosterone responses were muted in knockout mice after an acute stressor, but
exaggerated in response to the same stressor after undergoing sub-chronic stress.
Behavioural profiling of the alpha9-nAChR knockout mice in the home-cage revealed
that circadian patterns of activity were altered when compared to wildtype
controls. Furthermore, knockout mice showed altered responses to a period of
reward discounting, resulting in anhedonia-like behaviour in a sucrose preference
test where WT mice continued to seek reward. These experiments uncover a novel
role for the alpha9alpha10-nAChR in mounting a normal stress response and in the
regulation of affective- and reward-related behaviour, and suggest that pursuing
the receptor for clinical treatments may not be as straightforward as has been
suggested.
PMID- 28408299
TI - Ovarian hormones modify anxiety behavior and glucocorticoid receptors after
chronic social isolation stress.
AB - Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary
Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but
cycling estrogens could modify these behaviors. The aim of this study was to
determine if changes in ovarian hormones during the normal cycle could interact
with social isolation to alter anxiety and depressive-like behaviors. In
parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic
vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague
Dawley normal cycling female rats. We assigned rats to either isolated or paired
housing for 8 weeks. To assess anxiety and depressive-like behaviors, we used the
open field test and forced swim test, respectively. Female rats were tested at
either diestrus, estrus, or proestrus stage of the estrous cycle. After
behaviors, rats were perfused and brains collected. Brain sections containing
hippocampus and hypothalamus were analyzed using immunohistochemistry for
synaptophysin and glucocorticoid receptor (GR) levels. We found an increase in
depressive-like behaviors for isolated animals compared to paired housed rats,
regardless of the estrous cycle stage. Interestingly, we found a decrease in
anxiety behaviors in females in the estrus stage accompanied by a decrease in GR
expression in hippocampal DG and CA3. However, no changes in synaptophysin were
observed in any of the areas of studied. Our results support the beneficial
effects of circulating ovarian hormones in anxiety, possibly by decreasing GR
expression.
PMID- 28408301
TI - Impact of BRAF kinase inhibitors on the miRNomes and transcriptomes of melanoma
cells.
AB - BACKGROUND: Melanoma is an aggressive skin cancer with increasing incidence
worldwide. The development of BRAF kinase inhibitors as targeted treatments for
patients with BRAF-mutant tumours contributed profoundly to an improved overall
survival of patients with metastatic melanoma. Despite these promising results,
the emergence of rapid resistance to targeted therapy remains a serious clinical
issue. METHODS: To investigate the impact of BRAF inhibitors on miRNomes and
transcriptomes, we used in vitro melanoma models consisting of BRAF inhibitor
sensitive and -resistant cell lines generated in our laboratory. Subsequently,
microarray analyses were performed followed by RT-qPCR validations. RESULTS:
Regarding miRNome and transcriptome changes, the long-term effects of BRAF
inhibition differed in a cell line-specific manner with the two different BRAF
inhibitors inducing comparable responses in three melanoma cell lines. Despite
this heterogeneity, several miRNAs (e.g. miR-92a-1-5p, miR-708-5p) and genes
(e.g. DOK5, PCSK2) were distinctly differentially expressed in drug-resistant
versus -sensitive cell lines. Analyses of coexpressed miRNAs, as well as
inversely correlated miRNA-mRNA pairs, revealed a low MITF/AXL ratio in two drug
resistant cell lines that might be regulated by miRNAs. CONCLUSION: Several genes
and miRNAs were differentially regulated in the drug-resistant and -sensitive
cell lines and might be considered as prognostic and/or diagnostic resistance
biomarkers in melanoma drug resistance. GENERAL SIGNIFICANCE: Thus far, only
little information is available on the significance and role of miRNAs with
respect to kinase inhibitor treatments and emergence of drug resistance. In this
study, promising miRNAs and genes were identified and associated to BRAF
inhibitor-mediated resistance in melanoma. This article is part of a Special
Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest
Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue.
PMID- 28408302
TI - Pharmacokinetics of linezolid during continuous hemodiafiltration: A case report.
AB - The pharmacokinetics of linezolid clearance (CLLZD) during continuous
hemodiafiltration (CHDF) has not been comprehensively analyzed. Here, we examined
CLLZD by CHDF in a patient with septic shock and disseminated intravascular
coagulation due to methicillin-resistant Staphylococcus aureus. The extraction
ratio of LZD by CHDF was 22.6%, and the protein-binding rate was 17.9% +/- 7.7%.
In addition, it was determined that the calculated total body clearance of LZD
was 30.2 mL/min, plasma elimination half-life was 8.66 h, and the CLLZD by the
dialyzer used for CHDF was 23.0 mL/min. From the obtained pharmacokinetics, the
CLLZD of patients continuing CHDF was estimated to be approximately half of the
reported CLLZD for healthy subjects. In addition, the LZD concentration of the
sepsis patient who underwent CHDF remained higher than the minimum inhibitory
concentration and was similar to the LZD concentrations reported in normal renal
function patients. Although further studies are warranted, when LZD is
administered to patients treated with CHDF, the present findings suggest that
dose regulation is not required.
PMID- 28408303
TI - An infant case with hydrocephalus as the initial manifestation of Mycoplasma
hominis-associated meningitis.
AB - We report an infant with hydrocephalus as the initial manifestation of Mycoplasma
hominis-associated meningitis, who recovered without appropriate antimicrobial
treatment. The analysis of the 16S rRNA gene by polymerase chain reaction
amplification using universal primers and pathogen-specific primers was useful
for the diagnosis and the investigation of serial detection status of the
pathogen. This method may be helpful for the assessment of the frequency and the
prediction of severity in M. hominis-associated central nervous system infection
in infants, and investigating the association between M. hominis and the
development of hydrocephalus.
PMID- 28408304
TI - Analysis of IMP-1 type metallo-beta-lactamase-producing Acinetobacter
radioresistens isolated from companion animals.
AB - IMP-1 type metallo-beta-lactamase-producing (MBL-producing) Acinetobacter
radioresistens was isolated from a dog with cystitis and a cat with
conjunctivitis. The MBL-producing A. radioresistens isolates were resistant to
all of the beta-lactam antibiotics used in the sensitivity tests, but were
susceptible to gentamicin, amikacin, and minocycline. Also, one of the two
strains of A. radioresistens was susceptible to ciprofloxacin and levofloxacin.
These two cases were cured by administration of tetracyclines and
fluoroquinolones, which elicited a positive result in the sensitivity tests. This
report of the isolation of MBL-producing A. radioresistens in companion animals
is the first in the world. To prevent the proliferation of MBL-producing
bacteria, veterinary hospitals need to be aware of the behavior of MBL-producing
organisms.
PMID- 28408305
TI - Prevalence and Predictors of Early Heart Failure With Preserved Ejection Fraction
in Patients With Paroxysmal Atrial Fibrillation.
AB - BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of
diastolic dysfunction and heart failure. The purpose of this study was to
identify independent predictors of early (ie, only exercise-induced) heart
failure with preserved ejection fraction (HFpEF) and to describe the prevalence
of early HFpEF among patients with paroxysmal AF. METHODS AND RESULTS: One
hundred patients with paroxysmal AF and preserved left ventricular ejection
fraction (LVEF) underwent catheterization for left atrial pressure (LAP)
measurements at rest and at the peak of arm exercise (LAP-exe). Based on resting
and exercise LAP values, the patients were divided into 3 groups. Sixty-one
patients had no evidence of HFpEF (LAP at rest <=15 mm Hg, LAP-exe <25 mm Hg).
Twenty-five subjects had early HFpEF (LAP at rest <=15 mm Hg, LAP-exe >=25 mm Hg,
prevalence 25%). Fourteen patients already had HFpEF at rest (LAP at rest >15 mm
Hg). Multivariate exact logistic regression analysis identified age >=58 years,
LAP at rest >=11 mm Hg, and peak systolic mitral annular velocity <=9.3 cm/s to
be independent predictors of early HFpEF. CONCLUSIONS: In patients with
paroxysmal AF and preserved LVEF, there appears to be a clinically significant
prevalence of early HFpEF.
PMID- 28408306
TI - Heart Failure and Thermoregulatory Control: Can Patients With Heart Failure
Handle the Heat?
AB - Upon heat exposure, the thermoregulatory system evokes reflex increases in
sweating and skin blood flow responses to facilitate heat dissipation and
maintain heat balance to prevent the continuing rise in core temperature. These
heat dissipating responses are mediated primarily by autonomic and cardiovascular
adjustments; which, if attenuated, may compromise thermoregulatory control. In
patients with heart failure (HF), the neurohumoral and cardiovascular dysfunction
that underpins this condition may potentially impair thermoregulatory responses
and, consequently, place these patients at a greater risk of heat-related
illness. The aim of this review is to describe thermoregulatory mechanisms and
the factors that may increase the risk of heat-related illness in patients with
HF. An understanding of the mechanisms responsible for impaired thermoregulatory
control in HF patients is of particular importance, given the current and
projected increase in frequency and intensity of heat waves, as well as the
promotion of regular exercise as a therapeutic modality. Furthermore, novel
therapeutic strategies that may improve thermoregulatory control in HF, and the
clinical relevance of this work in this population will be discussed.
PMID- 28408307
TI - Mitochondrial respiratory chain disorganization in Parkinson's disease-relevant
PINK1 and DJ1 mutants.
AB - Brain mitochondrial complex I (CI) damage is associated with the loss of the
dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD)
patients. However, whether CI inhibition is associated with any alteration of the
mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To
address this issue, here we analyzed the MRC by blue native gel electrophoresis
(BNGE) followed by western blotting, in mitochondria purified from fibroblasts of
patients harboring PD-relevant Pink1 mutations. We found a decrease in free CI,
and in free versus supercomplexes (SCs)-assembled CI in PD; however, free complex
III (CIII) was only modestly affected, whereas its free versus SCs-assembled
forms decreased. Interestingly, complex IV (CIV) was considerably lost in the PD
samples. These results were largely confirmed in mitochondria isolated from
cultured neurons from Pink1-/- mice, and in cultured neurons and forebrain
samples from the PD-related Dj1-/- mice. Thus, besides CI damage, the MRC
undergoes a profound structural remodeling in PD likely responsible for the
energetic inefficiency and mitochondrial reactive oxygen species (mROS) over
production observed in this disease.
PMID- 28408308
TI - Effect of lipopolysaccharide on developmental competence of oocytes.
AB - In postpartum dairy cows, lipopolysaccharide (LPS) derived from gram-negative
bacteria such as Escherichia coli causes uterine inflammation resulting in low
fertility. The aim of this study was to determine the effect of LPS on the
developmental competence of bovine oocytes in vitro. LPS perturbed the nuclear
maturation of bovine oocytes by inhibiting meiotic progression. Although LPS did
not affect the copy number of mitochondrial DNA, it decreased mitochondrial
membrane potential in matured oocytes. LPS inhibited mitochondrial redistribution
throughout the cytoplasm. Oocytes matured under LPS treatment showed decreased
development to the blastocyst stage. Moreover, the trophoblast cell number of
blastocysts was significantly lower when the oocytes were matured in the presence
of LPS. Our findings suggest that LPS might impair the nuclear and cytoplasmic
maturation of oocytes and obstruct subsequent embryonic development in dairy
cows.
PMID- 28408309
TI - Evaluation of Feedback Systems for the Third-Year Surgical Clerkship.
AB - OBJECTIVE: To compare faculty-to-student feedback rates from 2 different data
sets: direct observation cards (direct evidence) and end-of-clerkship
questionnaires (ECQs, secondary student reporting). We as authors hypothesized
that direct evidence from observation cards would yield higher rates of feedback,
compared with student-reported ECQs. DESIGN: Data were gathered from 2
consecutive medical classes of the third-year surgical clerkship. Data were
analyzed retrospectively. Subjects and authors were blinded during data
collection and analysis. SETTING: University of Michigan Medical School (UMMS)
and University of Michigan Health System (UMHS). UMHS is an academic tertiary
care center, located in Ann Arbor, Michigan. PARTICIPANTS: Data were gathered
from all third-year medical students completing the surgical clerkship from 2012
to 2014. Data were available for 309 students, compared to 313 students who
graduated from UMMS during that time. RESULTS: Directly measured rates of
feedback showed higher rates of midclerkship feedback (95.43% vs 83.57%, p <
0.05), feedback on an observed history-taking (97.62% vs 84.87%, p < 0.05), and
feedback on an observed physical examination (99.67% vs 79.71%, p < 0.05), when
compared with the ECQ. CONCLUSION: These data suggest that solely using ECQs to
assess feedback rates may be inadequate. The use of multiple methods to assess
feedback may therefore be a prudent choice for surgical clerkships.
PMID- 28408310
TI - Patient satisfaction regarding outpatient mastectomy in Saint-Nazaire hospital
center.
AB - OBJECTIVES: To assess patient satisfaction with outpatient mastectomy and their
postoperative quality of life. MATERIALS AND METHODS: A retrospective descriptive
study was conducted of patients who had a mastectomy as outpatients at the
hospital of Saint-Nazaire between January 2013 and May 2015. Patients were
contacted by phone to answer a survey assessing their satisfaction. RESULTS: Out
of 16 eligible patients for an outpatient mastectomy, 11 patients were included
in our study (4 [25%] had to remain hospitalized after their intervention and one
patient could not be contacted). One patient (9%) presented a seroma requiring
aspiration. No patients were readmitted. All patients, except one, were satisfied
with the overall care. CONCLUSION: The management of outpatient mastectomies
seems to be a good option, provided that patients are motivated, properly
selected and well-informed prior to surgery.
PMID- 28408311
TI - Validation of a Difficulty Scoring System for Laparoscopic Liver Resection: A
Multicenter Analysis by the Endoscopic Liver Surgery Study Group in Japan.
AB - BACKGROUND: Laparoscopic liver resection (LLR) is widely used for hepatic disease
treatment. Preoperative prediction of operative difficulty can be beneficial as a
roadmap for surgeons advancing from simple to highly technical LLR. We performed
a multicenter analysis to investigate a "difficulty scoring system" for
predicting the difficulty of LLR. STUDY DESIGN: The proposed "difficulty scoring
system" includes 3 difficulty levels based on 5 factors. The system was validated
in a cohort of 2,199 patients who underwent LLR at 74 Japanese centers between
2010 and 2014; the difficulty level was rated as low (n = 965), intermediate (n =
891), and high (n = 343). Operative parameters, postoperative complications, and
outcomes were compared according to the difficulty levels. RESULTS: The median
operation time and blood loss were 258 minutes (range 30 to 1,275 minutes) and 75
mL (range 0 to 7,798 mL), respectively. The overall conversion rate was 5.0% (n =
110). The incidences of postoperative complications, liver failure, and in
hospital death were 5.3% (n = 116), 1.5% (n = 32), and 0.5% (n = 12),
respectively. Median hospital stay was 9 days (range 1 to 189 days). Conversion
rate, operation time, and blood loss showed a direct correlation with the
difficulty level. A strong correlation was observed among the difficulty level,
incidence of postoperative complications, and hospital stay. Incidence of
postoperative liver failure and in-hospital death in the high difficulty group
was higher than that in the low difficulty group. CONCLUSIONS: Preoperative
evaluation with the "difficulty scoring system" predicted the difficulty of the
operation and the postoperative outcomes of LLR. In the beginning of LLR
training, surgeons should start with low difficulty-level operations.
PMID- 28408312
TI - HCV-RNA quantification in liver bioptic samples and extrahepatic compartments,
using the abbott RealTime HCV assay.
AB - BACKGROUND & AIMS: We evaluated the performance of a rapid method to quantify HCV
RNA in the hepatic and extrahepatic compartments, by using for the first time the
Abbott RealTime HCV-assay. METHODS: Non-tumoral (NT), tumoral (TT) liver samples,
lymph nodes and ascitic fluid from patients undergoing orthotopic-liver
transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA
quantification; 5/22 patients were tested after or during direct acting
antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies
allowed normalization of HCV-RNA concentrations in IU/MUg of total RNA and IU/106
liver-cells, respectively. RESULTS: HCV-RNA was successfully quantified with high
reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the
17 untreated patients, a positive and significant HCV-RNA correlation between
serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA
treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in
all tested liver-tissues. Differently, only one DAA-treated patient, tested after
sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue.
CONCLUSIONS: HCV-RNA was successfully quantified with high reliability in liver
bioptic samples and extrahepatic compartments, even when HCV-RNA was
"undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for
HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic
sample is available.
PMID- 28408313
TI - Preventing cardiovascular heart disease: Promising nutraceutical and non
nutraceutical treatments for cholesterol management.
AB - Hypercholesterolemia is one of the major risk factors for the development of
cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia
causes many serious cardiovascular diseases. Statins are generally accepted as a
treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which
reduces coronary heart disease morbidity and mortality. Since statin use can be
associated with muscle problems and other adverse symptoms, non-adherence and
discontinuation of statin therapy often leads to inadequate control of plasma
cholesterol levels and increased cardiovascular risk. Moreover, there is
compelling evidence on the presence of still considerable residual cardiovascular
risk in statin-treated patients. Ezetimibe improves cholesterol-lowering efficacy
and provides mild additional cardiovascular protection when combined with statin
treatment. Despite a favorable safety profile compared to statins, ezetimibe
induced cholesterol-lowering is modest when used alone. Hence, there is a
critical need to identity additional effective hypolipidemic agents that can be
used either in combination with statins, or alone, if statins are not tolerated.
Thus, hypolipidemic agents such as proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitors, apolipoprotein B-100 antisense oligonucleotides, cholesteryl
ester transfer protein (CETP) inhibitors, and microsomal triglyceride transfer
protein (MTTP) inhibitors, as well as yeast polysaccharides (beta-glucans and
mannans) and compounds derived from natural sources (nutraceuticals) such as
glucomannans, plant sterols, berberine, and red yeast rice are being used. In
this review, we will discuss hypercholesterolemia, its impact on the development
of cardiovascular disease (CVD), and the use of yeast polysaccharides, various
nutraceuticals, and several therapeutic agents not derived from 'natural'
sources, to treat hypercholesterolemia.
PMID- 28408314
TI - Targeting endothelial metaflammation to counteract diabesity cardiovascular risk:
Current and perspective therapeutic options.
AB - The association of obesity and diabetes, termed "diabesity", defines a
combination of primarily metabolic disorders with insulin resistance as the
underlying common pathophysiology. Cardiovascular disorders associated with
diabesity represent the leading cause of morbidity and mortality in the Western
world. This makes diabesity, with its rising impacts on both health and
economics, one of the most challenging biomedical and social threats of present
century. The emerging comprehension of the genes whose alteration confers inter
individual differences on risk factors for diabetes or obesity, together with the
potential role of genetically determined variants on mechanisms controlling
responsiveness, effectiveness and safety of anti-diabetic therapy underlines the
need of additional knowledge on molecular mechanisms involved in the
pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the
unbalanced production of endothelial-derived vascular mediators, is known to be
present at the earliest stages of insulin resistance and obesity, and may precede
the clinical diagnosis of diabetes by several years. Once considered as a mere
consequence of metabolic abnormalities, it is now clear that endothelial
dysfunctional activity may play a pivotal role in the progression of diabesity.
In the vicious circle where vascular defects and metabolic disturbances worsen
and reinforce each other, a low-grade, chronic, and 'cold' inflammation
(metaflammation) has been suggested to serve as the pathophysiological link that
binds endothelial and metabolic dysfunctions. In this paradigm, it is important
to consider how traditional antidiabetic treatments (specifically addressing
metabolic dysregulation) may directly impact on inflammatory processes or
cardiovascular function. Indeed, not all drugs currently available to treat
diabetes possess the same anti-inflammatory potential, or target endothelial cell
function equally. Perspective strategies pointing at reducing metaflammation or
directly addressing endothelial dysfunction may disclose beneficial consequences
on metabolic regulation. This review focuses on existing and potential new
approaches ameliorating endothelial dysfunction and vascular inflammation in the
context of diabesity.
PMID- 28408315
TI - The CoRR hypothesis for genes in organelles.
AB - Chloroplasts and mitochondria perform energy transduction in photosynthesis and
respiration. These processes can be described in physico-chemical terms with no
obvious requirement for co-located genetic systems, separat from those of the
rest of the cell. Accordingly, biochemists once tended to regard endosymbiosis as
untestable evolutionary speculation. Lynn Sagan's seminal 1967 paper "On the
Origin of Mitosing Cells" outlined the evolution of eukaryotic cells by
endosymbiosis of prokaryotes. The endosymbiont hypothesis is consistent with
presence of DNA in chloroplasts and mitochondria, but does not assign it a
function. Biochemistry and molecular biology now show that Sagan's proposal has
an explanatory reach far beyond that originally envisaged. Prokaryotic origins of
photosynthetic and respiratory mechanisms are apparent in protein structural
insights into energy coupling. Genome sequencing confirms the underlying,
prokaryotic architecture of chloroplasts and mitochondria and illustrates the
profound influence of the original mergers of their ancestors' genes and proteins
with those of their host cells. Peter Mitchell's 1961 chemiosmotic hypothesis
applied the concept of vectorial catalysis that underlies biological energy
transduction and cell structure, function, and origins. Continuity of electrical
charge separation and membrane sidedness requires compartments within
compartments, together with intricate mechanisms for transport within and between
them. I suggest that the reason for the persistence of distinct genetic systems
within bioenergetic organelles is the selective advantage of subcellular co
location of specific genes with their gene products. Co-location for Redox
Regulation - CoRR - provides for a dialogue between chemical reduction-oxidation
and the action of genes encoding its protein catalysts. These genes and their
protein products are in intimate contact, and cannot be isolated from each other
without loss of an essential mechanism of adaptation of electron transport to
change in the external environment.
PMID- 28408316
TI - Down-regulation of LRP1B in colon cancer promoted the growth and migration of
cancer cells.
AB - Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of
colon cancer. It is of great interest to study the mechanism for the regulation
of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down
regulated in colon cancer tissues and inhibited the growth, migration and
metastasis of colon cancer cells. The molecular mechanism study revealed that
LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and
negatively regulated beta-catenin/TCF signaling. Taken together, our study
demonstrated the suppressive roles of LRP1B in the progression of colon cancer,
implicating that restoring the function of LRP1B would be a promising strategy
for the treatment of colon cancer.
PMID- 28408318
TI - Regulation of AGR2 expression via 3'UTR shortening.
AB - One recently discussed general mechanism affecting gene expression is 3'
untranslated region (3'UTR) length. Events such as shortening, translocation or
loss of 3'UTRs are observed within oncogenes and are proposed to associate with
increased expression. Thus, increased efforts are being made to understand
constitutive and differential transcript 3'end formation. Investigation of AGR2
mRNA revealed a direct impact of its 3'UTR length on AGR2 expression. In silico
analyses identified several regulatory sequences within the distal part of AGR2
mRNA that may regulate 3'UTR length and associated protein levels. Short 3'UTRs
were observed in a panel of AGR2-positive cancer cell lines and in human breast
cancer specimens, in which more extensive 3'UTR shortening correlated with
increased AGR2 protein levels. AGR2 is an important member of PI3K/AKT signalling
pathway, which along with the proposed involvement of mTOR in the regulation of
alternative polyadenylation, prompted us to study the role of mTOR in relation to
AGR2 mRNA 3'UTR shortening. A direct impact of mTOR signalling on AGR2 3'UTR
shortening associated with increased protein synthesis was found, which led to
the identification of a novel molecular mechanism involved in upregulation of
AGR2 levels in mTOR-activated cells via modulating the 3'UTR length of AGR2 mRNA.
PMID- 28408317
TI - Involvement of PUMA in pericyte migration induced by methamphetamine.
AB - Mounting evidence indicates that methamphetamine causes blood-brain barrier
damage, with emphasis on endothelial cells. The role of pericytes in
methamphetamine-induced BBB damage remains unknown. Our study demonstrated that
methamphetamine increased the migration of pericytes from the endothelial
basement membrane. However, the detailed mechanisms underlying this process
remain poorly understood. Thus, we examined the molecular mechanisms involved in
methamphetamine-induced pericyte migration. The results showed that exposure of
C3H/10T1/2 cells and HBVPs to methamphetamine increased PUMA expression via
activation of the sigma-1 receptor, MAPK and Akt/PI3K pathways. Moreover,
methamphetamine treatment resulted in the increased migration of C3H/10T1/2 cells
and HBVPs. Knockdown of PUMA in pericytes transduced with PUMA siRNA attenuated
the methamphetamine-induced increase in cell migration through attenuation of
integrin and tyrosine kinase mechanisms, implicating a role of PUMA in the
migration of C3H/10T1/2 cells and HBVPs. This study has demonstrated that
methamphetamine-mediated pericytes migration involves PUMA up-regulation. Thus,
targeted studies of PUMA could provide insights to facilitate the development of
a potential therapeutic approach for alleviation of methamphetamine-induced
pericyte migration.
PMID- 28408319
TI - Deriving and testing of dysplastic murine hepatocytes: A new platform in liver
cancer research.
AB - Dysplastic hepatocytes (DH) represent altered hepatocytes with potential for
malignant transformation. To date, most research on pathways to
hepatocarcinogenesis has focused on use of "hepatoma" cell lines derived from
hepatocellular carcinoma (HCC). We describe a novel technique for
deriving/culturing DH and demonstrate their utility for functional studies in
vitro, compared to primary hepatocytes (PH) and HCC. PH and DH were prepared by
portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently
subjected to FACS. HCC from diethylnitrosamine (DEN)-injected mice were
mechanically isolated. Cell cycle analyses were performed by flow cytometry and
PCNA immunohistochemistry. To establish utility of DH, we studied pathways of p53
turnover, apoptosis and cell proliferation using pfithrin-alpha (PFT) and nutlin
3. Like PH, DH were minimally proliferative compared to HCC. Only 30+/-0.03% of
DH were in G2/M phase versus 51+/-0.01% of HCC; this difference corroborated with
PCNA-immunostaining of dysplastic nodules from DEN-injected mice. In DH and HCC,
nutlin-3 suppressed p53 mRNA, induced p53 and mdm2 activation but paradoxically
resulted in increased anti-apoptotic and proliferative activity. Primary murine
DH display distinctive biological characteristics compared with PH and HCC. As an
intermediate cell type to HCC, they offer a new pathobiologically relevant
primary cell culture system with which to interrogate the molecular changes in
hepatocarcinogenesis.
PMID- 28408320
TI - Antibiotic self-treatment of travelers' diarrhea: It only gets worse!
PMID- 28408321
TI - Global health at the Human-Animal-Ecosystem Interface - An online course.
PMID- 28408322
TI - What role for lipoprotein(a) in clinical practice?
PMID- 28408324
TI - Recurrent breakdowns of mutualisms with ants in the neotropical ant-plant genus
Cecropia (Urticaceae).
AB - Mutualisms could be evolutionarily unstable, with changes in partner abundances
or in the spatial context of interactions potentially promoting their
dissolution. We test this prediction using the defense mutualisms between species
of the Neotropical genus Cecropia and Azteca ants. A new, multigene phylogeny
with representatives of all five genera of Cecropieae (most of them from the
Neotropics) and half of the 61 species of Cecropia shows the West African endemic
Musanga (2spp.) as sister to Cecropia, implying dispersal from the Neotropics to
Africa, with a molecular clock suggesting that this occurred about 23Mya.
Cecropia, a genus of neotropical pioneer trees, started diversifying ca. 8Mya. We
infer a single origin of specialized symbiosis with Azteca within Cecropia, eight
complete losses of this symbiosis, and a potential partner shift involving the
replacement of Azteca by Neoponera luteola ants. Niche space modeling based on
geo-referenced occurrences of over 9000 collections representing 58 of the 61
species of Cecropia, together with several comparative analyses, implies that
mutualism loss is concentrated at high altitudes and on Caribbean islands, with
the surprisingly frequent breakdowns potentially facilitated by low species
specificity of interacting Cecropia and Azteca mutualists.
PMID- 28408323
TI - Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery
disease: a mendelian randomisation analysis.
AB - BACKGROUND: The lipoprotein(a) pathway is a causal factor in coronary heart
disease. We used a genetic approach to distinguish the relevance of two distinct
components of this pathway, apolipoprotein(a) isoform size and circulating
lipoprotein(a) concentration, to coronary heart disease. METHODS: In this
mendelian randomisation study, we measured lipoprotein(a) concentration and
determined apolipoprotein(a) isoform size with a genetic method (kringle IV type
2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in
patients and controls (frequency matched for age and sex) from the Pakistan Risk
of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for
myocardial infarction per 1-SD difference in either LPA KIV2 repeats or
lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503
participants in PROMIS, we identified genetic variants associated with either
apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian
randomisation study design and genetic data on 60 801 patients with coronary
heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we
calculated ORs for myocardial infarction with variants that produced similar
differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a)
concentration. Finally, we compared phenotypic versus genotypic ORs to estimate
whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both
were causally associated with coronary heart disease. FINDINGS: The PROMIS cohort
included 9015 patients with acute myocardial infarction and 8629 matched
controls. In participants for whom KIV2 repeat and lipoprotein(a) data were
available, the OR for myocardial infarction was 0.93 (95% CI 0.90-0.97; p<0.0001)
per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a)
concentration and conventional lipid concentrations. The OR for myocardial
infarction was 1.10 (1.05-1.14; p<0.0001) per 1-SD increment in lipoprotein(a)
concentration, after adjustment for LPA KIV2 repeats and conventional lipids.
Genome-wide analysis identified rs2457564 as a variant associated with smaller
apolipoprotein(a) isoform size, but not lipoprotein(a) concentration, and
rs3777392 as a variant associated with lipoprotein(a) concentration, but not
apolipoprotein(a) isoform size. In 60 801 patients with coronary heart disease
and 123 504 controls, OR for myocardial infarction was 0.96 (0.94-0.98; p<0.0001)
per 1-SD increment in apolipoprotein(a) protein isoform size in serum due to
rs2457564, which was directionally concordant with the OR observed in PROMIS for
a similar change. The OR for myocardial infarction was 1.27 (1.07-1.50; p=0.007)
per 1-SD increment in lipoprotein(a) concentration due to rs3777392, which was
directionally concordant with the OR observed for a similar change in PROMIS.
INTERPRETATION: Human genetic data suggest that both smaller apolipoprotein(a)
isoform size and increased lipoprotein(a) concentration are independent and
causal risk factors for coronary heart disease. Lipoprotein(a)-lowering
interventions could be preferentially effective in reducing the risk of coronary
heart disease in individuals with smaller apolipoprotein(a) isoforms. FUNDING:
British Heart Foundation, US National Institutes of Health, Fogarty International
Center, Wellcome Trust, UK Medical Research Council, UK National Institute for
Health Research, and Pfizer.
PMID- 28408325
TI - Developmental control of spike-timing-dependent plasticity by tonic GABAergic
signaling in striatum.
AB - Activity-dependent long-term potentiation (LTP) and depression (LTD) of synaptic
strength underlie multiple forms of learning and memory. Spike-timing-dependent
plasticity (STDP) has been described as a Hebbian synaptic learning rule that
could account for experience-dependent changes in neural networks, but little is
known about whether and how STDP evolves during development. We previously showed
that GABAergic signaling governs STDP polarity and thus operates as a
Hebbian/anti-Hebbian switch in the striatum. Although GABAergic networks are
subject to important developmental maturation, it remains unclear whether STDP is
developmentally shaped by GABAergic signaling. Here, we investigated whether STDP
rules are developmentally regulated at corticostriatal synapses in the
dorsolateral striatum. We found that striatal STDP displays unidirectional
plasticity (Hebbian tLTD) in young rats (P7-10) whereas STDP is bidirectional and
anti-Hebbian in juvenile (P20-25) and adult (P60-90) rats. We also provide
evidence that the appearance of tonic (extrasynaptic) GABAergic signaling from
the juvenile stage is a crucial factor in shaping STDP rules during development,
establishing bidirectional anti-Hebbian STDP in the adult striatum. Thus,
developmental maturation of GABAergic signaling tightly drives the polarity of
striatal plasticity.
PMID- 28408326
TI - EMP1, EMP 2, and EMP3 as novel therapeutic targets in human cancer.
AB - The epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, and EMP3) belong
to the peripheral myelin protein 22-kDa (PMP22) gene family, which consists of at
least seven members: PMP22, EMP1, EMP2, EMP3, PERP, brain cell membrane protein
1, and MP20. This review addresses the structural and functional features of
EMPs, detailing their tissue distribution and functions in the human body, their
expression pattern in a variety of tumors, and highlighting the underlying
mechanisms involved in carcinogenesis. The implications in cancer biology,
patient prognosis prediction, and potential application in disease therapy are
discussed. For example, EMP1 was reported to be a biomarker of gefitinib
resistance in lung cancer and contributes to prednisolone resistance in acute
lymphoblastic leukemia patients. EMP2 functions as an oncogene in human
endometrial and ovarian cancers; however, characteristics of EMP2 in urothelial
cancer fulfill the criteria of a suppressor gene. Of particular interest, EMP3
overexpression in breast cancer is significantly related to strong HER-2
expression. Co-expression of HER-2 and EMP3 is the most important indicator of
progression-free and metastasis-free survival for patients with urothelial
carcinoma of the upper urinary tract. Altogether, discovery of pharmacological
inhibitors and/or regulators of EMP protein activity could open novel strategies
for enhanced therapy against EMP-mediated human diseases.
PMID- 28408327
TI - Morbidity and mortality after surgery for nonmalignant colorectal polyps.
AB - BACKGROUND AND AIMS: Despite evidence that most nonmalignant colorectal polyps
can be managed endoscopically, a substantial proportion of patients with a
nonmalignant colorectal polyp are still sent to surgery. Risks associated with
this surgery are not well characterized. We describe 30-day postoperative
morbidity and mortality and explore risk factors for adverse events in patients
undergoing surgical resection for nonmalignant colorectal polyps. METHODS: We
analyzed data collected prospectively as part of the National Surgical Quality
Improvement Program. Our analysis included 12,732 patients who underwent elective
surgery for a nonmalignant colorectal polyp from 2011 through 2014. We report
adverse events within 30 days of the index surgery. Modified Poisson regression
was used to estimate risk ratios and 95% confidence intervals. RESULTS: Thirty
day mortality was .7%. The risk of a major postoperative adverse event was 14%.
Within 30 days of resection, 7.8% of patients were readmitted and 3.6% of
patients had a second major surgery. The index surgery resulted in a colostomy in
1.8% and ileostomy in .4% of patients. Patients who had surgical resection of a
nonmalignant polyp in the rectum or anal canal compared with the colon had a risk
ratio of 1.58 (95% confidence interval, 1.09-2.28) for surgical site infection
and 6.51 (95% confidence interval, 4.97-8.52) for ostomy. CONCLUSIONS: Surgery
for a nonmalignant colorectal polyp is associated with significant morbidity and
mortality. A better understanding of the risks and benefits associated with
surgical management of nonmalignant colorectal polyps will better inform
discussions regarding the relative merits of management strategies.
PMID- 28408330
TI - Muscarinic cholinoreceptors (M1-, M2-, M3- and M4-type) modulate the
acetylcholine secretion in the frog neuromuscular junction.
AB - Muscarinic cholinoreceptors regulate the neurosecretion process in vertebrate
neuromuscular junctions. The diversity of muscarinic effects on acetylcholine
(ACh) secretion may be attributed to the different muscarinic subtypes involved
in this process. In the present study, the location of five muscarinic receptor
subtypes (M1, M2, M3, M4 and M5) on the motor nerve terminals of frog cutaneous
pectoris muscle was shown using specific polyclonal antibodies. The modulatory
roles of these receptors were investigated via assessment of the effects of
muscarine and specific muscarinic antagonists on the quantal content of endplate
currents (EPCs) and the time course of secretion, which was estimated from the
distribution of "real" synaptic delays of EPCs recorded in a low Ca2+/high Mg2+
solution. The agonist muscarine decreased the EPC quantal content and
synchronized the release process. The depressing action of muscarine on the EPC
quantal content was abolished only by pretreatment of the preparation with the M3
blockers 4-DAMP (1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide) and J 104129
fumarate ((alphaR)-alpha-Cyclopentyl-alpha-hydroxy-N-[1-(4-methyl-3-pentenyl)-4
piperidinyl]benzeneacetamide fumarate). Moreover, antagonists of the M1, M2, M3
and M4 receptors per se diminished the intensity of secretion, which suggests a
putative up-regulation of the release by endogenous ACh.
PMID- 28408328
TI - TRPA1 expression levels and excitability brake by KV channels influence cold
sensitivity of TRPA1-expressing neurons.
AB - The molecular sensor of innocuous (painless) cold sensation is well-established
to be transient receptor potential cation channel, subfamily M, member 8 (TRPM8).
However, the role of transient receptor potential cation channel, subfamily A,
member 1 (TRPA1) in noxious (painful) cold sensation has been controversial. We
find that TRPA1 channels contribute to the noxious cold sensitivity of mouse
somatosensory neurons, independent of TRPM8 channels, and that TRPA1-expressing
neurons are largely non-overlapping with TRPM8-expressing neurons in mouse dorsal
root ganglia (DRG). However, relatively few TRPA1-expressing neurons (e.g.,
responsive to allyl isothiocyanate or AITC, a selective TRPA1 agonist) respond
overtly to cold temperature in vitro, unlike TRPM8-expressing neurons, which
almost all respond to cold. Using somatosensory neurons from TRPM8-/- mice and
subtype-selective blockers of TRPM8 and TRPA1 channels, we demonstrate that
responses to cold temperatures from TRPA1-expressing neurons are mediated by
TRPA1 channels. We also identify two factors that affect the cold-sensitivity of
TRPA1-expressing neurons: (1) cold-sensitive AITC-sensitive neurons express
relatively more TRPA1 transcripts than cold-insensitive AITC-sensitive neurons
and (2) voltage-gated potassium (KV) channels attenuate the cold-sensitivity of
some TRPA1-expressing neurons. The combination of these two factors, combined
with the relatively weak agonist-like activity of cold temperature on TRPA1
channels, partially explains why few TRPA1-expressing neurons respond to cold.
Blocking KV channels also reveals another subclass of noxious cold-sensitive DRG
neurons that do not express TRPM8 or TRPA1 channels. Altogether, the results of
this study provide novel insights into the cold-sensitivity of different
subclasses of somatosensory neurons.
PMID- 28408329
TI - Highest dominant frequency and rotor positions are robust markers of driver
location during noninvasive mapping of atrial fibrillation: A computational
study.
AB - BACKGROUND: Dominant frequency (DF) and rotor mapping have been proposed as
noninvasive techniques to guide localization of drivers maintaining atrial
fibrillation (AF). OBJECTIVE: The purpose of this study was to evaluate the
robustness of both techniques in identifying atrial drivers noninvasively under
the effect of electrical noise or model uncertainties. METHODS: Inverse-computed
DFs and phase maps were obtained from 30 different mathematical AF simulations.
Epicardial highest dominant frequency (HDF) regions and rotor location were
compared with the same inverse-computed measurements after addition of noise to
the ECG, size variations of the atria, and linear or angular deviations in the
atrial location inside the thorax. RESULTS: Inverse-computed electrograms (EGMs)
individually correlated poorly with the original EGMs in the absence of induced
uncertainties (0.45 +/- 0.12) and were worse with 10-dB noise (0.22 +/- 0.11), 3
cm displacement (0.01 +/- 0.02), or 36 degrees rotation (0.02 +/- 0.03).
However, inverse-computed HDF regions showed robustness against induced
uncertainties: from 82% +/- 18% match for the best conditions, down to 73% +/-
23% for 10-dB noise, 77% +/- 21% for 5-cm displacement, and 60% +/- 22% for 36
degrees rotation. The distance from the inverse-computed rotor to the original
rotor was also affected by uncertainties: 0.8 +/- 1.61 cm for the best
conditions, 2.4 +/- 3.6 cm for 10-dB noise, 4.3 +/- 3.2 cm for 4-cm displacement,
and 4.0 +/- 2.1 cm for 36 degrees rotation. Restriction of rotor detections to
the HDF area increased rotor detection accuracy from 4.5 +/- 4.5 cm to 3.2 +/-
3.1 cm (P <.05) with 0-dB noise. CONCLUSION: The combination of frequency and
phase-derived measurements increases the accuracy of noninvasive localization of
atrial rotors driving AF in the presence of noise and uncertainties in atrial
location or size.
PMID- 28408331
TI - Evaluation of effect of minocycline on rewarding potential and alcohol relapse in
place preference model in mice.
AB - INTRODUCTION: Medical management for alcohol abuse has limitations. Alcohol
consumption activates N-methyl-d-aspartate receptors and release of nitric oxide
which can be inhibited by minocycline as it readily crosses blood brain barrier
and may have effect on alcohol consumption. Thus, study objective is to evaluate
the effect of minocycline on rewarding property, extinction and the reinstatement
phenomenon induced by alcohol in a model of conditioned place preference (CPP) in
mice. METHODOLOGY: To evaluate rewarding effects of alcohol, CPP procedure
consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day
2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and
10) and postconditioning test (day 11) conducted on 11 consecutive days. The
groups included were saline treated group (alcohol control), naltrexone - 1mg/kg
(positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To
evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6
parts, the first 4 were the same as enumerated above followed by extinction (days
12-16) and reinstatement phase (day 17). RESULTS: The time spent in alcohol
paired compartment by different groups, revealed that minocycline and naltrexone
significantly attenuated alcohol-induced place preference compared to alcohol
control (p<0.05). Pretreatment with minocycline and naltrexone blocked
reinstatement of extinguished CPP. CONCLUSION: Minocycline may have a role in
attenuating the rewarding property of alcohol and prevent alcohol relapse.
PMID- 28408332
TI - Molecular cloning, structural modeling, and expression analysis of MyD88 and
IRAK4 of golden pompano (Trachinotus ovatus).
AB - MyD88 and IRAK4 are important components of TLR signaling pathways. However,
information about MyD88 and IRAK4 is vacant in golden pompano (Trachinotus
ovatus), a marine teleost with great commercial value. Thus, in this study the
full lengths of trMyD88 and trIRAK4 were cloned from golden pompano using RT-PCR
and RACE-PCR methods. trMyD88 was 1213 bp in length, encoding a putative protein
of 288 amino acids (aa), consisting of a 99 aa of death domain at its N-terminal
and a 137 aa of the TIR domain at its C-terminal. trIRAK4 was 1606 bp in length,
encoding a putative protein of 469 aa, including an N-terminal death domain and a
central kinase domain, connected by a ProST domain. Other domains or aa residues
needed for their functions were also identified in trMyD88 and trIRAK4.
Physicochemical features and 3-D structures of trMyD88 and trIRAK4 were also
analyzed. Quantitative real-time PCR revealed that the 2 genes were ubiquitously
expressed in tissues from healthy pompano, especially highly in the spleen and
head kidney, indicating their roles in the immune response. Further, trMyD88 and
trIRAK4 were up-regulated at 12 h after the Vibrio alginilyticus and polyI:C
challenge and continued to 48 h post challenge. Our results demonstrated that
MyD88 and IRAK4 played important roles in the golden pompano innate immune
system, providing the basis for further study of the signaling pathways that
these 2 genes are involved in.
PMID- 28408333
TI - Trans-generational enhancement of C-type lysozyme level in eggs of zebrafish by
dietary beta-glucan.
AB - beta-glucan has been shown to increase non-specific immunity and resistance
against infections or pathogenic bacteria in several fish species, but
information regarding its trans-generational immune-enhancing effects is still
rather limited. Lysozyme is a maternal immune factor playing an important role in
the developing embryos of zebrafish. Here we clearly showe that beta-glucan
enhanced the level of C-type lysozyme in eggs of zebrafish, and the embryos
derived from beta-glucan-treated zebrafish were more resistant to bacterial
challenge than control embryos. Moreover, the transferred lysozyme was apparently
linked with the antimicrobial defense of early embryos. In addition, we also
showed that beta-glucan induced a significant increase in the synthesis of C-type
lysozyme in previtellogenetic oocytes. Therefore, we show for the first time that
beta-glucan can enhance the lysozyme level in offspring via both inducing the
transfer of the molecule from mothers to eggs and stimulating its endogenous
production in oocytes.
PMID- 28408334
TI - The transcription factor Relish controls Anaplasma marginale infection in the
bovine tick Rhipicephalus microplus.
AB - Rhipicephalus microplus is an important biological vector of Anaplasma marginale,
the etiological agent of bovine anaplasmosis. The knowledge of tick immune
responses to control bacterial infections remains limited. In this study, we
demonstrate that transcription factor Relish from the IMD signaling pathway has
an important role in the control of A. marginale infection in ticks. We found
that RNA-mediated silencing of Relish caused a significant increase in the number
of A. marginale in the midgut and salivary glands of R. microplus. In addition,
the IMD pathway regulates the expression of the gene that encodes the
antimicrobial peptide (AMP) microplusin. Moreover, microplusin expression was up
regulated in the midgut (2*) and salivary glands (8*) of A. marginale infected R.
microplus. Therefore, it is plausible to hypothesize that microplusin may be
involved in the A. marginale control. This study provides the first evidence of
IMD signaling pathway participation on the A. marginale control in R. microplus.
PMID- 28408336
TI - Hospital-acquired Urinary Tract Infections in Neonatal ICU Patients: Is Voiding
Cystourethrogram Necessary?
AB - OBJECTIVE: To evaluate the radiographic findings of neonatal intensive care unit
(NICU) patients diagnosed with hospital-acquired urinary tract infection (UTI).
MATERIALS AND METHODS: Children with no preexisting genitourinary anomalies
undergoing a voiding cystourethrogram (VCUG) for culture-documented UTI during
NICU admission were identified. Demographics, microbiology results, and imaging
findings were evaluated. RESULTS: A total of 147 NICU patients underwent VCUG
during the study period. Of these, the indication for VCUG was UTI in 58
children. Neonates diagnosed with UTI were born at a mean gestational age of 28
3/7 +/- 4 3/7 weeks, and underwent VCUG at a mean of age of 70.3 +/- 42 days.
Urine culture grew Enterococcus in 32 (55.2%), Enterobacter in 6 (10.3%),
coagulase negative staphylococcus in 6 (10.3%), Escherichia coli in 5 (8.7%), and
other in 9 infants (15.5%). All patients underwent a retroperitoneal ultrasound,
which was read as normal in 31 patients (53.4%). Fourteen children (24.1%)
diagnosed with UTI were found to have vesicoureteral reflux on VCUG. On
univariate analysis, no patient characteristics were associated with VCUG
positivity. On multivariate analysis, the effect of age at VCUG differed by renal
bladder ultrasound results. Patients with an abnormal ultrasound were 3.6 (95%
confidence interval, 1.39-9.24) times more likely to have a positive VCUG for
every 1 month increase in age. CONCLUSION: Ultrasound anomalies are common in
NICU patients diagnosed with UTI. The effect of age at VCUG differed by
ultrasound result; the probability of vesicoureteral reflux in infants with
sonographic abnormalities and UTI increases with age.
PMID- 28408335
TI - Optimizing delivery of a behavioral pain intervention in cancer patients using a
sequential multiple assignment randomized trial SMART.
AB - BACKGROUND/AIMS: Pain is common in cancer patients and results in lower quality
of life, depression, poor physical functioning, financial difficulty, and
decreased survival time. Behavioral pain interventions are effective and
nonpharmacologic. Traditional randomized controlled trials (RCT) test
interventions of fixed time and dose, which poorly represent successive treatment
decisions in clinical practice. We utilize a novel approach to conduct a RCT, the
sequential multiple assignment randomized trial (SMART) design, to provide
comparative evidence of: 1) response to differing initial doses of a pain coping
skills training (PCST) intervention and 2) intervention dose sequences adjusted
based on patient response. We also examine: 3) participant characteristics
moderating intervention responses and 4) cost-effectiveness and practicality.
METHODS/DESIGN: Breast cancer patients (N=327) having pain (ratings>=5) are
recruited and randomly assigned to: 1) PCST-Full or 2) PCST-Brief. PCST-Full
consists of 5 PCST sessions. PCST-Brief consists of one 60-min PCST session. Five
weeks post-randomization, participants re-rate their pain and are re-randomized,
based on intervention response, to receive additional PCST sessions, maintenance
calls, or no further intervention. Participants complete measures of pain
intensity, interference and catastrophizing. CONCLUSIONS: Novel RCT designs may
provide information that can be used to optimize behavioral pain interventions to
be adaptive, better meet patients' needs, reduce barriers, and match with
clinical practice. This is one of the first trials to use a novel design to
evaluate symptom management in cancer patients and in chronic illness; if
successful, it could serve as a model for future work with a wide range of
chronic illnesses.
PMID- 28408337
TI - Is Body Mass Index the Best Adiposity Measure for Prostate Cancer Risk? Results
From a Veterans Affairs Biopsy Cohort.
AB - OBJECTIVE: To test multiple adiposity measures and prostate cancer (PC) risk in
men undergoing prostate biopsy. We hypothesized that body mass index (BMI), body
fat, and waist circumference would be highly correlated, and all would be
associated with aggressive PC, but not overall risk. SUBJECTS AND METHODS: A case
(483)-control (496) study among men undergoing prostate biopsy from 2007 to 2016
was conducted at the Durham Veterans Affairs Medical Center. Anthropometric and
self-reported measurements were taken. Percent body fat was measured.
Associations between adiposity measures and PC risk and high-grade PC (Gleason
>=7) were examined using logistic regression. RESULTS: BMI, percent body fat, and
waist circumference were highly correlated (rho >= .79) (P < .001). On
multivariable analysis, BMI (P = .011) was associated with overall PC risk, but
percent body fat (P = .16) and waist circumference (P = .19) were not. However,
all adiposity measurements were associated with high-grade disease (P < .001). We
found a strong relationship between self-reported and measured weight (rho = .97)
and height (rho = .92). CONCLUSION: BMI, body fat, and waist circumference were
all highly correlated and associated with aggressive PC. This study supports the
idea that higher adiposity is selectively associated with high-grade PC and
reinforces the continued use of self-reported BMI as a measure of obesity in
epidemiologic studies of PC.
PMID- 28408338
TI - The Value of Urodynamics in an Academic Specialty Referral Practice.
AB - OBJECTIVE: To describe and evaluate the use of urodynamics (UDS) studies for all
indications in an academic specialty referral urology practice. MATERIALS AND
METHODS: This is a prospective questionnaire-based study wherein clinicians
completed a pre- and post-UDS questionnaire on each UDS that they ordered for all
clinical indications between May 2013 and August 2014. Questions pertained to
patient demographics and history, the clinical indication for the UDS, the
clinician's pre- and post-UDS clinical impressions, and changes in post-UDS
management plans. Pre- and post-UDS diagnoses were compared using the McNemar
test. RESULTS: Clinicians evaluated a total of 285 UDS studies during the study
period. The average age of study participants was 56.0 (+/-16.4) years, 59.5%
were female, and 29.3% had a neurologic diagnosis. The most common indication for
performing UDS was to discern the predominant type of urinary incontinence
(stress vs urgency) in patients with mixed incontinence symptoms (38.5%) and to
assess the safety of the bladder during filling (38.2%). UDS statistically
significantly changed the ordering clinician's clinical impression of the
patient's lower urinary tract diagnosis for stress urinary incontinence and for
urgency and urgency urinary incontinence (both had P values of <.05). Fluoroscopy
was found to be helpful in 29.5% of urodynamic studies, and clinicians reported
that UDS changed their treatment plans in 42.5% of the studies, most commonly
pertaining to changes related to surgery (35.0%). CONCLUSION: Overall, UDS was a
clinically useful tool that altered the clinical impression and treatment plan in
a large percentage of carefully selected patients.
PMID- 28408339
TI - A Retroperitoneal Serous Cystadenoma of Mullerian Origin Masquerading as a
Massive Renal Cyst.
AB - A 78-year-old woman presented to the urology clinic with a large, symptomatic
left-sided abdominal cyst that was believed to be renal in etiology for many
years and that had been percutaneously drained 3 times previously with persistent
regrowth. The patient underwent laparoscopic resection of this mass, which proved
to be a completely distinct retroperitoneal cystic structure and was not renal in
nature. Pathologic analysis ultimately revealed a rare occurrence: a benign
retroperitoneal Mullerian serous cystadenoma. To our knowledge, this is the first
report of such an entity "disguised" as a renal cyst.
PMID- 28408340
TI - Nogo-A in the visual system development and in ocular diseases.
AB - Nogo-A is a potent myelin-associated inhibitor for neuronal growth and plasticity
in the central nervous system (CNS). Its effects are mediated by the activation
of specific receptors that intracellularly control cytoskeleton rearrangements,
protein synthesis and gene expression. Moreover, Nogo-A has been involved in the
development of the visual system and in a variety of neurodegenerative diseases
and injury processes that can alter its function. For example, Nogo-A was shown
to influence optic nerve myelinogenesis, the formation and maturation of retinal
axon projections, and retinal angiogenesis. In adult animals, the inactivation of
Nogo-A exerted remarkable effects on visual plasticity. Relieving Nogo-A-induced
inhibition increased axonal sprouting after optic nerve lesion and axonal
rewiring in the visual cortex of intact adult mice. This review aims at
presenting our current knowledge on the role of Nogo-A in the visual system and
to discuss how its therapeutic targeting may promote visual improvement in
ophthalmic diseases.
PMID- 28408341
TI - Lipidomics in biomedical research-practical considerations.
AB - Lipids have many central physiological roles including as structural components
of cell membranes, energy storage sources and intermediates in signaling
pathways. Lipid-related disturbances are known to underlie many diseases and
their co-morbidities. The emergence of lipidomics has empowered researchers to
study lipid metabolism at the cellular as well as physiological levels at a
greater depth than was previously possible. The key challenges ahead in the field
of lipidomics in medical research lie in the development of experimental
protocols and in silico techniques needed to study lipidomes at the systems
level. Clinical questions where lipidomics may have an impact in healthcare
settings also need to be identified, both from the health outcomes and health
economics perspectives. This article is part of a Special Issue entitled:
BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein.
PMID- 28408342
TI - Chronic ethanol intake induces partial microglial activation that is not reversed
by long-term ethanol withdrawal in the rat hippocampal formation.
AB - Neuroinflammation has been implicated in the pathogenesis of several disorders.
Activation of microglia leads to the release of pro-inflammatory mediators and
microglial-mediated neuroinflammation has been proposed as one of the alcohol
induced neuropathological mechanisms. The present study aimed to examine the
effect of chronic ethanol exposure and long-term withdrawal on microglial
activation and neuroinflammation in the hippocampal formation. Male rats were
submitted to 6 months of ethanol treatment followed by a 2-month withdrawal
period. Stereological methods were applied to estimate the total number of
microglia and activated microglia detected by CD11b immunohistochemistry in the
hippocampal formation. The expression levels of the pro-inflammatory cytokines
TNF-alpha, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was
associated with an increase in the total number of activated microglia but
morphological assessment indicated that microglia did not exhibit a full
activation phenotype. These data were supported by functional evidence since
chronic alcohol consumption produced no changes in the expression of TNF-alpha or
COX-2. The levels of IL-15 a cytokine whose expression is increased upon
activation of both astrocytes and microglia, was induced by chronic alcohol
treatment. Importantly, the partial activation of microglia induced by ethanol
was not reversed by long-term withdrawal. This study suggests that chronic
alcohol exposure induces a microglial phenotype consistent with partial
activation without significant increase in classical cytokine markers of
neuroinflammation in the hippocampal formation. Furthermore, long-term cessation
of alcohol intake is not sufficient to alter the microglial partial activation
phenotype induced by ethanol.
PMID- 28408343
TI - The impact of cellular senescence in skin ageing: A notion of mosaic and
therapeutic strategies.
AB - Cellular senescence is now recognized as one of the nine hallmarks of ageing.
Recent data show the involvement of senescent cells in tissue ageing and some age
related diseases. Skin represents an ideal model for the study of ageing. Indeed,
skin ageing varies between individuals depending on their chronological age but
also on their exposure to various exogenous factors (mainly ultraviolet rays). If
senescence traits can be detected with ageing in the skin, the senescent
phenotype varies among the various skin cell types. Moreover, the origin of
cellular senescence in the skin is still unknown, and multiple origins are
possible. This reflects the mosaic of skin ageing. Senescent cells can interfere
with their microenvironment, either via the direct secretion of factors (the
senescence-associated secretory phenotype) or via other methods of communication,
such as extracellular vesicles. Knowledge regarding the impact of cellular
senescence on skin ageing could be integrated into dermatology research,
especially to limit the appearance of senescent cells after photo(chemo)therapy
or in age-related skin diseases. Therapeutic approaches include the clearance of
senescent cells via the use of senolytics or via the cooperation with the immune
system.
PMID- 28408344
TI - Repurposing bacterial toxins for intracellular delivery of therapeutic proteins.
AB - Despite enormous efforts, achieving efficacious levels of proteins inside
mammalian cells remains one of the greatest challenges in biologics-based drug
discovery and development. The inability of proteins to readily cross biological
membranes precludes access to the wealth of intracellular targets and
applications that lie within mammalian cells. Existing methods of delivery
commonly suffer from an inability to target specific cells and tissues, poor
endosomal escape, and limited in vivo efficacy. The aim of the present commentary
is to highlight the potential of certain classes of bacterial toxins, which
naturally deliver a large protein into the cytosolic compartment of target cells
after binding a host cell-surface receptor with high affinity, as robust protein
delivery platforms. We review the progress made in recent years toward
demonstrating the utility of these systems at delivering a wide variety of
protein cargo, with special attention paid to three distinct toxin-based
platforms. We contend that with recent advances in protein deimmunization
strategies, bacterial toxins are poised to introduce biologics into the inner
sanctum of cells and treat a wealth of heretofore untreatable diseases with a new
generation of therapeutics.
PMID- 28408346
TI - WITHDRAWN: Mercy: The Human Difference.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
business/policies/article-withdrawal.
PMID- 28408345
TI - Icariin protects against glucocorticoid induced osteoporosis, increases the
expression of the bone enhancer DEC1 and modulates the PI3K/Akt/GSK3beta/beta
catenin integrated signaling pathway.
AB - Osteoporosis is a serious public health concern worldwide. Herba epimedii has
been used for centuries and even thousands of years to treat osteoporotic
conditions. Icariin, a flavonol glycoside, is one of the major active
ingredients. In this study, we have shown that icariin protected against
glucocorticoid-induced osteoporotic changes in SaoS-2 cells and mice. We have
also shown that dexamethasone (a glucocorticoid) suppressed and icariin induced
DEC1, a structurally distinct helix-loop-helix protein. DEC1 overexpression
promoted whereas DEC1 knockdown decreased osteogenic activity. Likewise, DEC1
overexpression and knockdown inversely regulated the expression of beta-catenin
and PIK3CA, an essential player in the Wnt/beta-catenin and PI3K/Akt signaling
pathways, respectively. Interestingly, DKK1, an inhibitor of Wnt/beta-catenin
signaling inhibitor, and LY294002, an inhibitor of PI3K/Akt signaling, abolished
the induction of DEC1 by icariin. It is established that these two pathways are
interconnected by the phosphorylation status of GSK3beta. Dexamethasone decreased
but icariin increased GSK3beta phosphorylation. Finally, DEC1 deficient mice
developed osteoporotic phenotypes. Taken together, it is concluded that DEC1
likely supports the action of icariin against glucocorticoid induced osteoporosis
with an involvement of the PI3K/Akt/GSK3beta/beta-catenin integrated signaling
pathway.
PMID- 28408347
TI - PC-FACS.
AB - PC-FACS(FastArticleCriticalSummaries for Clinicians inPalliativeCare) provides
hospice and palliative care clinicians with concise summaries of the most
important findings from more than 100 medical and scientific journals. If you
have colleagues who would benefit from receiving PC-FACS, please encourage them
to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc
facs@aahpm.org.
PMID- 28408348
TI - Design and in vivo evaluation of solid lipid nanoparticulate systems of
Olanzapine for acute phase schizophrenia treatment: Investigations on
antipsychotic potential and adverse effects.
AB - The present paper discusses the design, characterization and in vivo evaluation
of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic
drug for acute schizophrenia treatment, during which hospitalization is mandatory
and adverse effects are at its peak. The solid lipid nanoparticulate system was
obtained by emulsification-ultra sonication technique wherein three factors such
as solid lipid content, concentration of surfactant and drug: solid lipid ratio
were selected at three different levels in order to study their influence on
significant characteristic responses such as particle size, encapsulation
efficiency and drug content. A Box Behnken design with 17 runs involving whole
factors at three levels was employed for the study. The optimized formulation was
further coated with Polysorbate 80 in order to enhance its brain targeting
potential through endocytosis transport process via blood brain barrier. The
designed formulations were pre-clinically tested successfully in Wistar rat model
for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse
effects (weight gain study for 28days). The results obtained indicated that solid
lipid nanoparticles had very narrow size distribution (151.29+/-3.36nm) with very
high encapsulation efficiency (74.51+/-1.75%). Morphological studies by SEM have
shown that solid lipid nanoparticles were spherical in shape with smooth surface.
Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release
of drug for 48h, as found by the in vitro release studies. The formulations also
exhibited high redispersibility after freeze-drying and stability study results
demonstrated good stability, with no significant change for a period of 6months.
In vivo evaluation and adverse effects studies of Olanzapine-loaded
nanoparticulate systems in animal model have demonstrated an improved therapeutic
efficacy than pure Olanzapine. The antipsychotic effect of drug loaded
nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic
action of pure Olanzapine solution. The weight gain studies for 28days
demonstrated a significant inhibition in weight gain for Olanzapine-loaded
nanoparticulate systems as compared to the pure Olanzapine. The present research
findings indicate that OLN-loaded nanoparticulate systems may be highly promising
for effective delivery of Olanzapine with better efficacy and minimum adverse
effects.
PMID- 28408349
TI - Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during
Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in
Pigs.
AB - BACKGROUND: Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis
resulting in severe injury to the heart and brain and an overall survival of less
than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor
outcomes following prolonged CA. However, the onset and severity of mitochondrial
dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully
understood. Ischemic postconditioning (IPC), controlled pauses during the
initiation of CPR, has been shown to improve cardiac function and neurologically
favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial
dysfunction develops during prolonged CA and can be rescued with IPC during CPR
(IPC-CPR). METHODS: A total of 63 swine were randomized to no ischemia (Naive),
19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of
CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR.
Mitochondria were isolated from the heart and brain to quantify respiration, rate
of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species
(ROS) production was quantified from fresh frozen heart and brain tissue.
RESULTS: Compared to Naive, Untreated VF induced cardiac and brain ROS
overproduction concurrent with decreased mitochondrial respiratory coupling and
CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR
attenuated brain ROS overproduction but had no other effect on mitochondrial
function in the heart or brain. Compared to Untreated VF, IPC-CPR improved
cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and
decreased ROS overproduction in the heart and brain. CONCLUSIONS: Fifteen minutes
of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and
increased ROS production in the heart and brain. IPC-CPR attenuates cardiac
mitochondrial dysfunction caused by prolonged VF CA after only 4min of
reperfusion, suggesting that IPC-CPR is an effective intervention to reduce
cardiac injury. However, reperfusion with both CPR methods had limited effect on
mitochondrial function in the brain, emphasizing an important physiological
divergence in post-arrest recovery between those two vital organs.
PMID- 28408350
TI - Neuroactive steroid levels and psychiatric and andrological features in post
finasteride patients.
AB - Recent reports show that, in patients treated with finasteride for male pattern
hair loss, persistent side effects including sexual side effects, depression,
anxiety and cognitive complaints may occur. We here explored the psychiatric and
andrological features of patients affected by post-finasteride syndrome (PFS) and
verified whether the cerebrospinal fluid (CSF) and plasma levels of neuroactive
steroids (i.e., important regulators of nervous function) are modified. We found
that eight out of sixteen PFS male patients considered suffered from a DSM-IV
major depressive disorder (MDD). In addition, all PFS patients showed erectile
dysfunction (ED); in particular, ten patients showed a severe and six a mild
moderate ED. We also reported abnormal somatosensory evoked potentials of the
pudendal nerve in PFS patients with severe ED, the first objective evidence of a
neuropathy involving peripheral neurogenic control of erection. Testicular volume
by ultrasonography was normal in PFS patients. Data obtained on neuroactive
steroid levels also indicate interesting features. Indeed, decreased levels of
pregnenolone, progesterone and its metabolite (i.e., dihydroprogesterone),
dihydrotestosterone and 17beta-estradiol and increased levels of
dehydroepiandrosterone, testosterone and 5alpha-androstane-3alpha,17beta-diol
were observed in CSF of PFS patients. Neuroactive steroid levels were also
altered in plasma of PFS patients, however these changes did not reflect exactly
what occurs in CSF. Finally, finasteride did not only affect, as expected, the
levels of 5alpha-reduced metabolites of progesterone and testosterone, but also
the further metabolites and precursors suggesting that this drug has broad
consequence on neuroactive steroid levels of PFS patients.
PMID- 28408352
TI - Characterization and spatiotemporal expression of gonadotropin-releasing hormone
in the Pacific abalone, Haliotis discus hannai.
AB - Gonadotropin-releasing hormone (GnRH) is a key neuropeptide regulating
reproduction in humans and other vertebrates. Recently, GnRH-like cDNAs and
peptides were reported in marine mollusks, implying that GnRH-mediated
reproduction is an ancient neuroendocrine system that arose prior to the
divergence of protostomes and deuterostomes. Here, we evaluated the reproductive
control system mediated by GnRH in the Pacific abalone Haliotis discus hannai. We
cloned a prepro-GnRH cDNA (Hdh-GnRH) from the pleural-pedal ganglion (PPG) in H.
discus hannai, and analyzed its spatiotemporal gene expression pattern. The open
reading frame of Hdh-GnRH encodes a protein of 101 amino acids, consisting of a
signal peptide, a GnRH dodecapeptide, a cleavage site, and a GnRH-associated
peptide. This structure and sequence are highly similar to GnRH-like peptides
reported for mollusks and other invertebrates. Quantitative polymerase chain
reaction demonstrated that Hdh-GnRH mRNA was more strongly expressed in the
ganglions (PPG and cerebral ganglion [CG]) than in other tissues (gonads, gills,
intestine, hemocytes, muscle, and mantle) in both sexes. In females, the
expression levels of Hdh-GnRH mRNA in the PPG and branchial ganglion (BG) were
significantly higher at the ripe and partial spent stages than at the early and
late active stages. In males, Hdh-GnRH mRNA levels in the BG showed a significant
increase in the partial spent stage. Unexpectedly, Hdh-GnRH levels in the CG were
not significantly different among the examined stages in both sexes. These
results suggest that Hdh-GnRH mRNA expression profiles in the BG and possibly the
PPG are tightly correlated with abalone reproductive activities.
PMID- 28408351
TI - Inhibition of heat shock protein 90 rescues glucocorticoid-induced bone loss
through enhancing bone formation.
AB - Endogenous glucocorticoids (GCs) support normal bone development and bone mass
maintenance, whereas long-term exposure to pharmacological dosages of GCs
uncouples bone formation and resorption, resulting in GC-induced osteoporosis
(GIOP). Heat shock protein 90 (HSP90) chaperoning glucocorticoid receptor (GR)
signaling prompts us to speculate that HSP90 plays critical roles in GC-mediated
bone formation and GIOP. In the present study, inhibition of HSP90 activity by 17
Demethoxy-17-allyaminogeldanmycin (17-AAG) or knockdown of HSP90 expression by
siRNAs attenuated dexamethasone(Dex)-induced GR nuclear accumulation and
transcriptional output of GR signaling, whereas overexpression of HSP90alpha or
HSP90beta enhanced GR transactivity in C3H10T1/2 cells. Though 17-AAG itself
enhanced osteoblastic differentiation, it restored the Dex(10-8M)-induced and
Dex(10-6M)-negated osteoblastic differentiation in C3H10T1/2 cells and primary
calvarial osteoblasts. Moreover, systemic administration of 17-AAG to mice
induced not only osteoclastogenesis but also osteoblastogenesis, whereas bone
formation possibly exceeded bone resorption, eventually leading to the increased
bone masses. Likewise, systemic administration of 17-AAG to mice restored GC
negated osteoblastogenesis and enhanced GC-induced osteoclastogenesis, similarly,
17-AAG-induced bone formation possibly exceeded both 17-AAG- and GC-induced bone
resorption, eventually resulting in rescue of GIOP. Together, the present study
has revealed that inhibition of HSP90 restores GIOP through enhancing bone
formation, and our findings may help to shed light on the pathogenesis of GIOP
and provide targets for the therapeutic intervention of the disease.
PMID- 28408353
TI - ZEB1 induced miR-99b/let-7e/miR-125a cluster promotes invasion and metastasis in
esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive
tumors in Asia. Recent researches demonstrate that miRNAs are involved in the
development of ESCC. In this study, we identified a miRNA cluster, termed miR
99b/let-7e/miR-125a as pro-metastasis oncomir. Overexpression of this miRNA
cluster promoted ESCC cell migration and invasion in vitro and induced an
experimental metastasis in vivo. ZEB1 was discovered to bind to the promoter
region of miR-99b/let-7e/miR-125a cluster and regulate the expression of miRNAs
at transcriptional level. Knockdown of ZEB1 resulted in a decrease of both mature
and primary miRNAs. Further research revealed AT-rich interaction domain 3A
(ARID3A) as a direct target of miR-99b/let-7e/miR-125a cluster. Reduced ARID3A
phenocopied miR-99b/let-7e/miR-125a overexpression, and elevated ARID3A
counteracted the pro-metastasis effect of miR-99b/let-7e/miR-125a. Moreover,
ARID3A was downregulated by ZEB1 in a miR-99b/let-7e/miR-125a dependent manner.
Collectively, our study sheds light on the essential role of miR-99b/let-7e/miR
125a cluster in tumor metastasis.
PMID- 28408354
TI - Therapeutic effects of Argyrin F in pancreatic adenocarcinoma.
AB - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited
treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived
from the myxobacterium Archangium gephyra, shows antitumoral activities. We
hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression.
We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+)
to assess AF anticancer activity. We analyzed the effect of AF on proliferation
and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation
, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF,
Gemcitabine (G) and combinational treatment (AF + G) was performed for survival
analysis. AF inhibited cell proliferation, migration, invasion and colony
formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused
considerable apoptosis and senescence in a dose- and time-dependent manner and
affected cell cycle G1/S phase transition. G treatment achieved longest mice
survival, followed by AF + G and AF compared to vehicle group. However, AF + G
treatment induced the largest reduction in tumor spread and ascites. In
conclusion, we have demonstrated that AF prevents PDAC progression and that
combined therapy was superior to AF monotherapy. Therefore, AF treatment might be
useful as an additional therapy for PDAC.
PMID- 28408355
TI - Down-regulation of DLC1 in endothelial cells compromises the angiogenesis
process.
AB - DLC1 is a RhoGAP-containing tumor suppressor that inhibits angiogenesis by
repressing VEGF production in epithelial cells. Here we report the roles of DLC1
in endothelial cells. Silencing of DLC1 (siDLC1) enhances cell migration but
reduces tube formation activities of human umbilical vein endothelial cells
(HUVECs). Biochemically, RhoA activity and paxillin protein level are markedly
increased in siDLC1 HUVECs. Although further silencing of RhoA restores the cell
migration phenotype, the tube formation defect and up-regulated paxillin level
remain unchanged. On the other hand, paxillin knockdown rescues tube formation
and migration phenotypes but not the up-regulated RhoA activity. These results
indicate that DLC1 regulates endothelial cell migration through RhoA and paxillin
independently and controls tube formation mainly via paxillin. To further
determine endothelial DLC1's function, we have generated endothelial specific
knockout mice (DLC1-Tek). DLC1-Tek mice appear to be normal and healthy but their
angiogenesis processes are compromised as shown in gel plug and aortic ring
sprouting assays. Analysis of endothelial cells isolated from DLC1-Tek mice has
further affirmed the cellular and biochemical phenotypes established in siDLC1
HUVECs. Our studies have demonstrated a positive regulatory role of endothelial
DLC1 in angiogenesis.
PMID- 28408356
TI - Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway
inhibitor, in mice model of Schistosoma-induced liver fibrosis.
AB - Liver fibrosis is a pathological process complicating schistosomiasis. It is an
active process of continuous extracellular matrix accumulation. In Egypt,
schistosomiasis re-infection is a continuing problem especially in rural areas.
In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a
hedgehog-pathway inhibitor as a new molecular target for Schistosoma-induced
liver fibrosis, in addition to exploring its effect as antischistosomal drug. The
effect of GDC-0449 alone or combined with Praziquantel was tried experimentally
in infected mice with Schistosoma mansoni. Fifty CD-1 Swiss female albino mice
were used, forty mice were infected with Schistosoma mansoni cercariae. Animals
were grouped into five groups; uninfected control, infected untreated, infected
treated with Praziquantel (500mg/kg/day) for two days, infected treated with GDC
0449 (40mg/kg/day) for seven days, and infected treated with combined
Praziquantel and GDC-0449. Parasitological and chemical parameters,
hydroxyproline level and liver granuloma were assessed. Liver fibrosis was
reduced significantly evidenced by reduced hydroxyproline levels [P<0.01 for
combined (Praziquantel/GDC-0449) treatment groups, P<0.001 for GDC-0449-treated
group]. Also, histopathological examination of liver tissues revealed that the
mean diameter of granulomas was statistically reduced (P=0.001) with a reduction
rate of 24.4% on treatment with GDC-0449. In GDC-0449/Praziquantel combined
treatment group, number and mean diameter of the granulomas were reduced
significantly P<0.001, and P=0.001 respectively. No antischistosomal effect was
recorded for GDC-0449 in this study.
PMID- 28408357
TI - Critical flicker frequency: A stethoscope for minimal hepatic encephalopathy
evaluation.
PMID- 28408358
TI - A microbial signature for Crohn's disease.
PMID- 28408359
TI - Personal Communication Device Use by Nurses Providing In-Patient Care: Survey of
Prevalence, Patterns, and Distraction Potential.
AB - BACKGROUND: Coincident with the proliferation of employer-provided mobile
communication devices, personal communication devices, including basic and
enhanced mobile phones (smartphones) and tablet computers that are owned by the
user, have become ubiquitous among registered nurses working in hospitals. While
there are numerous benefits of personal communication device use by nurses at
work, little is known about the impact of these devices on in-patient care.
OBJECTIVE: Our aim was to examine how hospital-registered nurses use their
personal communication devices while doing both work-related and non-work-related
activities and to assess the impact of these devices on in-patient care. METHODS:
A previously validated survey was emailed to 14,797 members of two national
nursing organizations. Participants were asked about personal communication
device use and their opinions about the impact of these devices on their own and
their colleagues' work. RESULTS: Of the 1268 respondents (8.57% response rate),
only 5.65% (70/1237) never used their personal communication device at work
(excluding lunch and breaks). Respondents self-reported using their personal
communication devices at work for work-related activities including checking or
sending text messages or emails to health care team members (29.02%, 363/1251),
as a calculator (25.34%, 316/1247), and to access work-related medical
information (20.13%, 251/1247). Fewer nurses reported using their devices for non
work-related activities including checking or sending text messages or emails to
friends and family (18.75%, 235/1253), shopping (5.14%, 64/1244), or playing
games (2.73%, 34/1249). A minority of respondents believe that their personal
device use at work had a positive effect on their work including reducing stress
(29.88%, 369/1235), benefiting patient care (28.74%, 357/1242), improving
coordination of patient care among the health care team (25.34%, 315/1243), or
increasing unit teamwork (17.70%, 220/1243). A majority (69.06%, 848/1228) of
respondents believe that on average personal communication devices have a more
negative than positive impact on patient care and 39.07% (481/1231) reported that
personal communication devices were always or often a distraction while working.
Respondents acknowledged their own device use negatively affected their work
performance (7.56%, 94/1243), or caused them to miss important clinical
information (3.83%, 47/1225) or make a medical error (0.90%, 11/1218).
Respondents reported witnessing another nurse's use of devices negatively affect
their work performance (69.41%, 860/1239), or cause them to miss important
clinical information (30.61%, 378/1235) or make a medical error (12.51%,
155/1239). Younger respondents reported greater device use while at work than
older respondents and generally had more positive opinions about the impact of
personal communication devices on their work. CONCLUSIONS: The majority of
registered nurses believe that the use of personal communication devices on
hospital units raises significant safety issues. The high rate of respondents who
saw colleagues distracted by their devices compared to the rate who acknowledged
their own distraction may be an indication that nurses are unaware of their own
attention deficits while using their devices. There were clear generational
differences in personal communication device use at work and opinions about the
impact of these devices on patient care. Professional codes of conduct for
personal communication device use by hospital nurses need to be developed that
maximize the benefits of personal communication device use, while reducing the
potential for distraction and adverse outcomes.
PMID- 28408360
TI - Technology Use and Preferences for Mobile Phone-Based HIV Prevention and
Treatment Among Black Young Men Who Have Sex With Men: Exploratory Research.
AB - BACKGROUND: Black young men who have sex with men (BYMSM) experience higher human
immunodeficiency virus (HIV) incidence than their white and Latino counterparts.
OBJECTIVE: The aim of our study was to understand BYMSM's preferences for mobile
phone-based HIV prevention and treatment in order to inform culturally tailored
interventions to reduce the spread of HIV and improve HIV treatment outcomes in
this population. METHODS: Qualitative focus groups (N=6) with BYMSM aged 18-29
years (N=41; 46%, 19/41 HIV-positive) were conducted to elucidate their
preferences for the design and delivery of mobile phone-based HIV prevention and
treatment interventions. A modified grounded theory approach to data analysis was
undertaken using ATLAS.ti textual analysis software. RESULTS: Participants
preferred holistic health interventions that did not focus exclusively on HIV
prevention and treatment. Issues of privacy and confidentiality were paramount.
Participants preferred functionality that enables discreet connections to
culturally competent health educators and treatment providers who can address the
range of health and psychosocial concerns faced by BYMSM. CONCLUSIONS: Mobile
phone-based HIV prevention has the potential to increase engagement with HIV
prevention and treatment resources among BYMSM. For these approaches to be
successful, researchers must include BYMSM in the design and creation of these
interventions.
PMID- 28408361
TI - Design of a Mobile App for Nutrition Education (TreC-LifeStyle) and Formative
Evaluation With Families of Overweight Children.
AB - BACKGROUND: Nutrition and diet apps represent today a popular area of mobile
health (mHealth), offering the possibility of delivering behavior change (BC)
interventions for healthy eating and weight management in a scalable and cost
effective way. However, if commercial apps for pediatric weight management fail
to retain users because of a lack of theoretical background and evidence-based
content, mHealth apps that are more evidence-based are found less engaging and
popular among consumers. Approaching the apps development process from a
multidisciplinary and user-centered design (UCD) perspective is likely to help
overcome these limitations, raising the chances for an easier adoption and
integration of nutrition education apps within primary care interventions.
OBJECTIVE: The aim of this study was to describe the design and development of
the TreC-LifeStyle nutrition education app and the results of a formative
evaluation with families. METHODS: The design of the nutrition education
intervention was based on a multidisciplinary UCD approach, involving a team of
BC experts, working with 2 nutritionists and 3 pediatricians from a primary care
center. The app content was derived from evidence-based knowledge founded on the
Food Pyramid and Mediterranean Diet guidelines used by pediatricians in primary
care. A formative evaluation of the TreC-LifeStyle app involved 6 families of
overweight children (aged 7-12 years) self-reporting daily food intake of
children for 6 weeks and providing feedback on the user experience with the
mHealth intervention. Analysis of the app's usage patterns during the
intervention and of participants' feedback informed the refinement of the app
design and a tuning of the nutrition education strategies to improve user
engagement and compliance with the intervention. RESULTS: Design sessions with
the contribution of pediatricians and nutritionists helped define the nutrition
education app and intervention, providing an effective human and virtual coaching
approach to raise parents' awareness about children's eating behavior and
lifestyle. The 6 families participating in the pilot study found the app usable
and showed high compliance with the intervention over the 6 weeks, but analysis
of their interaction and feedback showed the need for improving some of the app
features related to the BC techniques "monitoring of the behavior" and
"information provision." CONCLUSIONS: The UCD and formative evaluation of TreC
LifeStyle show that nutrition education apps are feasible and acceptable
solutions to support health promotion interventions in primary care.
PMID- 28408362
TI - eHealth Search Patterns: A Comparison of Private and Public Health Care Markets
Using Online Panel Data.
AB - BACKGROUND: Patient and consumer access to eHealth information is of crucial
importance because of its role in patient-centered medicine and to improve
knowledge about general aspects of health and medical topics. OBJECTIVES: The
objectives were to analyze and compare eHealth search patterns in a private
(United States) and a public (United Kingdom) health care market. METHODS: A new
taxonomy of eHealth websites is proposed to organize the largest eHealth
websites. An online measurement framework is developed that provides a precise
and detailed measurement system. Online panel data are used to accurately track
and analyze detailed search behavior across 100 of the largest eHealth websites
in the US and UK health care markets. RESULTS: The health, medical, and lifestyle
categories account for approximately 90% of online activity, and e-pharmacies,
social media, and professional categories account for the remaining 10% of online
activity. Overall search penetration of eHealth websites is significantly higher
in the private (United States) than the public market (United Kingdom). Almost
twice the number of eHealth users in the private market have adopted online
search in the health and lifestyle categories and also spend more time per
website than those in the public market. The use of medical websites for specific
conditions is almost identical in both markets. The allocation of search effort
across categories is similar in both the markets. For all categories, the vast
majority of eHealth users only access one website within each category. Those
that conduct a search of two or more websites display very narrow search
patterns. All users spend relatively little time on eHealth, that is, 3-7 minutes
per website. CONCLUSIONS: The proposed online measurement framework exploits
online panel data to provide a powerful and objective method of analyzing and
exploring eHealth behavior. The private health care system does appear to have an
influence on eHealth search behavior in terms of search penetration and time
spent per website in the health and lifestyle categories. Two explanations are
offered: (1) the personal incentive of medical costs in the private market
incentivizes users to conduct online search; and (2) health care information is
more easily accessible through health care professionals in the United Kingdom
compared with the United States. However, the use of medical websites is almost
identical, suggesting that patients interested in a specific condition have a
motivation to search and evaluate health information, irrespective of the health
care market. The relatively low level of search in terms of the number of
websites accessed and the average time per website raise important questions
about the actual level of patient informedness in both the markets. Areas for
future research are outlined.
PMID- 28408363
TI - WittyFit-Live Your Work Differently: Study Protocol for a Workplace-Delivered
Health Promotion.
AB - BACKGROUND: Morbidity before retirement has a huge cost, burdening both public
health and workplace finances. Multiple factors increase morbidity such as stress
at work, sedentary behavior or low physical activity, and poor nutrition
practices. Nowadays, the digital world offers infinite opportunities to interact
with workers. The WittyFit software was designed to understand holistic issues of
workers by promoting individualized behavior changes at the workplace. OBJECTIVE:
The shorter term feasibility objective is to demonstrate that effective use of
WittyFit will increase well-being and improve health-related behaviors. The mid
term objective is to demonstrate that WittyFit improves economic data of the
companies such as productivity and benefits. The ultimate objective is to
increase life expectancy of workers. METHODS: This is an exploratory
interventional cohort study in an ecological situation. Three groups of
participants will be purposefully sampled: employees, middle managers, and
executive managers. Four levels of engagement are planned for employees:
commencing with baseline health profiling from validated questionnaires;
individualized feedback based on evidence-based medicine; support for behavioral
change; and formal evaluation of changes in knowledge, practices, and health
outcomes over time. Middle managers will also receive anonymous feedback on
problems encountered by employees, and executive top managers will have
indicators by division, location, department, age, seniority, gender and
occupational position. Managers will be able to introduce specific initiatives in
the workplace. WittyFit is based on two databases: behavioral data (WittyFit) and
medical data (WittyFit Research). Statistical analyses will incorporate morbidity
and well-being data. When a worker leaves a workplace, the company documents one
of three major explanations: retirement, relocation to another company, or
premature death. Therefore, WittyFit will have the ability to include mortality
as an outcome. WittyFit will evolve with the waves of connected objects further
increasing its data accuracy. Ethical approval was obtained from the ethics
committee of the University Hospital of Clermont-Ferrand, France. RESULTS:
WittyFit recruitment and enrollment started in January 2016. First publications
are expected to be available at the beginning of 2017. CONCLUSIONS: The name
WittyFit came from Witty and Fitness. The concept of WittyFit reflects the
concept of health from the World Health Organization: being spiritually and
physically healthy. WittyFit is a health-monitoring, health-promoting tool that
may improve the health of workers and health of companies. WittyFit will evolve
with the waves of connected objects further increasing its data accuracy with
objective measures. WittyFit may constitute a powerful epidemiological database.
Finally, the WittyFit concept may extend healthy living into the general
population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02596737;
https://www.clinicaltrials.gov/ct2/show/NCT02596737 (Archived by WebCite at
http://www.webcitation.org/6pM5toQ7Y).
PMID- 28408364
TI - A Content Analysis of Health and Safety Communications Among Internet-Based Sex
Work Advertisements: Important Information for Public Health.
AB - BACKGROUND: The capacity to advertise via the Internet continues to contribute to
the shifting dynamics in adult commercial sex work. eHealth interventions have
shown promise to promote Internet-based sex workers' health and safety
internationally, yet minimal attention has been paid in Canada to developing such
interventions. Understanding the information communicated in Internet-based sex
work advertisements is a critical step in knowledge development to inform such
interventions. OBJECTIVE: The purpose of this content analysis was to increase
our understanding of the health and safety information within the Internet
advertisements among women, men, and transgender sex workers and to describe how
this information may be utilized to inform eHealth service development for this
population. METHODS: A total of 75 Internet-based sex worker advertisements (45
women, 24 men, and 6 transgender persons) were purposefully selected from 226
advertisements collected as part of a larger study in Western Canada. Content
analysis was employed to guide data extraction about demographic characteristics,
sexual services provided, service restrictions, health practices and concerns,
safety and security, and business practices. Frequencies for each variable were
calculated and further classified by gender. Thematic analysis was then
undertaken to situate the communications within the social and commercialized
contexts of the sex industry. RESULTS: Four communications themes were
identified: (1) demographic characteristics; (2) sexual services; (3) health; and
(4) safety and security. White was the most common ethnicity (46/75, 61%) of
advertisements. It was found that 20-29 years of age accounted for 32 of the 51
advertisements that provided age. Escort, the only legal business title, was the
most common role title used (48/75, 64%). In total, 85% (64/75) of advertisements
detailed lists of sexual services provided and 41% (31/75) of advertisements
noted never offering uncovered services (ie, no condom). Gender and the type of
Web-based platform mattered for information communicated. It was found that 35 of
the 45 women's advertisements were situated in personal websites and hosted
details about nonsexual aspects of an appointment. Men and transworkers used
Internet classified advertisement platforms with predetermined categories.
Communications about sexually transmitted infections (STIs) occurred in only 16%
(12/75) of advertisements with men accounting for 7. Women's advertisements
accounted for 26 of the 37 advertisements noting safety restrictions. Zero men or
transpersons restricted alcohol or drug use. In total, 75% (56/75) of
advertisements offered out-call services and the average minimal hourly rate
ranged from Can $140/h to Can $200/h. CONCLUSIONS: The study findings contribute
to understandings about the diverse platforms used in commercial sex
advertisements, and how sex workers frame information for potential clients. This
information affords health care providers and policy makers insights to how they
might assist with promoting the health of Internet-based sex workers and their
clients.
PMID- 28408366
TI - Acute brain trauma, lung injury, and pneumonia: more than just altered mental
status and decreased airway protection.
AB - Traumatic brain injury (TBI) is a major cause of mortality and morbidity
worldwide. Even when patients survive the initial insult, there is significant
morbidity and mortality secondary to subsequent pulmonary edema, acute lung
injury (ALI), and nosocomial pneumonia. Whereas the relationship between TBI and
secondary pulmonary complications is recognized, little is known about the
mechanistic interplay of the two phenomena. Changes in mental status secondary to
acute brain injury certainly impair airway- and lung-protective mechanisms.
However, clinical and translational evidence suggests that more specific neuronal
and cellular mechanisms contribute to impaired systemic and lung immunity that
increases the risk of TBI-mediated lung injury and infection. To better
understand the cellular mechanisms of that immune impairment, we review here the
current clinical data that support TBI-induced impairment of systemic and lung
immunity. Furthermore, we also review the animal models that attempt to reproduce
human TBI. Additionally, we examine the possible role of damage-associated
molecular patterns, the chlolinergic anti-inflammatory pathway, and sex
dimorphism in post-TBI ALI. In the last part of the review, we discuss current
treatments and future pharmacological therapies, including fever control,
tracheostomy, and corticosteroids, aimed to prevent and treat pulmonary edema,
ALI, and nosocomial pneumonia after TBI.
PMID- 28408367
TI - Variability in Chromatin Architecture and Associated DNA Repair at Genomic
Positions Containing Somatic Mutations.
AB - Dynamic chromatin structures result in differential chemical reactivity to
mutational processes throughout the genome. To identify chromatin features
responsible for mutagenesis, we compared chromatin architecture around single
nucleotide variants (SNV), insertion/deletions (indels), and their context
matched, nonmutated positions. We found epigenetic differences between genomic
regions containing missense SNVs and those containing frameshift indels across
multiple cancer types. Levels of active histone marks were higher around
frameshift indels than around missense SNV, whereas repressive histone marks
exhibited the reverse trend. Accumulation of repressive histone marks and
nucleosomes distinguished mutated positions (both SNV and indels) from the
context-matched, nonmutated positions, whereas active marks were associated with
substitution- and cancer type-specific mutagenesis. We also explained mutagenesis
based on genome maintenance mechanisms, including nucleotide excision repair
(NER), mismatch repair (MMR), and DNA polymerase epsilon (POLE). Regional NER
variation correlated strongly with chromatin features; NER machineries exhibited
shifted or depleted binding around SNV, resulting in decreased NER at mutation
positions, especially at sites of recurrent mutations. MMR-deficient tumors
selectively acquired SNV in regions with high active histone marks, especially
H3K36me3, whereas POLE-deficient tumors selectively acquired indels and SNV in
regions with low active histone marks. These findings demonstrate the importance
of fine-scaled chromatin structures and associated DNA repair mechanisms in
mutagenesis. Cancer Res; 77(11); 2822-33. (c)2017 AACR.
PMID- 28408365
TI - Immunomodulators targeting MARCO expression improve resistance to postinfluenza
bacterial pneumonia.
AB - Downregulation of the alveolar macrophage (AM) receptor with collagenous
structure (MARCO) leads to susceptibility to postinfluenza bacterial pneumonia, a
major cause of morbidity and mortality. We sought to determine whether
immunomodulation of MARCO could improve host defense and resistance to secondary
bacterial pneumonia. RNAseq analysis identified a striking increase in MARCO
expression between days 9 and 11 after influenza infection and indicated
important roles for Akt and Nrf2 in MARCO recovery. In vitro, primary human AM
like monocyte-derived macrophages (AM-MDMs) and THP-1 macrophages were treated
with IFNgamma to model influenza effects. Activators of Nrf2 (sulforaphane) or
Akt (SC79) caused increased MARCO expression and a MARCO-dependent improvement in
phagocytosis in IFNgamma-treated cells and improved survival in mice with
postinfluenza pneumococcal pneumonia. Transcription factor analysis also
indicated a role for transcription factor E-box (TFEB) in MARCO recovery.
Overexpression of TFEB in THP-1 cells led to marked increases in MARCO. The
ability of Akt activation to increase MARCO expression in IFNgamma-treated AM
MDMs was abrogated in TFEB-knockdown cells, indicating Akt increases MARCO
expression through TFEB. Increasing MARCO expression by targeting Nrf2 signaling
or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial
clearance and survival in postinfluenza bacterial pneumonia.
PMID- 28408368
TI - Neonatal airway: challenging endotracheal intubation in infants with tracheal
malformations at birth.
AB - Intubating newborn infants can be exacting. We describe two cases of endotracheal
intubations in infants born with tracheal malformations. A male infant aged 30
weeks required intubation at birth for respiratory distress. Repeated attempts at
intubation failed to achieve an optimal endotracheal tube position as the tube
could not advance beyond the vocal cords. Hence ventilation continued with
suboptimal air entry in the lungs. Bronchoscopy and CT scan confirmed tracheal
stenosis. Slide tracheoplasty was successfully executed on day 78 of life. A
female infant aged 33 weeks was intubated at birth for perinatal depression.
Attempts at intubation were unsuccessful due to non-visualisation of the
laryngeal inlet. Oesophagus was intubated and attempts to inflate showed air
entry in the lungs, suggesting a fistulous communication between oesophagus and
airway. A contrast oesophagogram showed a fistula connecting oesophagus and
carina. With airway patency in question and associated major anomalies, parents
were counselled and support was withdrawn.
PMID- 28408369
TI - Is tonsillectomy recommended in adults with recurrent tonsillitis?
PMID- 28408371
TI - Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by
Regulating PPARgamma-Dependent Monocyte Differentiation and Function.
AB - OBJECTIVE: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates
inflammatory and potentially proatherogenic effects, whereas the role of
intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of
nicotinamide adenine dinucleotide (NAD)+ generation, in atherogenesis is largely
unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes
on inflammation and atherosclerosis. APPROACH AND RESULTS: Low-density
lipoprotein receptor-deficient mice with hematopoietic overexpression of human
iNAMPT (iNAMPThi), on a western type diet, showed attenuated plaque burden with
features of lesion stabilization. This anti-atherogenic effect was caused by
improved resistance of macrophages to apoptosis by attenuated chemokine (C-C
motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage
polarization toward an anti-inflammatory M2 phenotype. The iNAMPThi phenotype was
almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating
that iNAMPT catalytic activity is instrumental in the atheroprotection.
Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and
eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted
an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least
partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome
proliferator-activated receptor gamma. Finally, iNAMPT and peroxisome
proliferator-activated receptor gamma showed a strong correlation in human
atherosclerotic, but not healthy arteries, hinting to a relevance of
iNAMPT/peroxisome proliferator-activated receptor gamma pathway also in human
carotid atherosclerosis. CONCLUSIONS: This study highlights the functional
dichotomy of intracellular versus extracellular NAMPT, and unveils a critical
role for the iNAMPT-peroxisome proliferator-activated receptor gamma axis in
atherosclerosis.
PMID- 28408372
TI - Effects of Sugar-Sweetened Beverage Consumption on Microvascular and
Macrovascular Function in a Healthy Population.
AB - OBJECTIVE: To assess vascular function during acute hyperglycemia induced by
commercial sugar-sweetened beverage (SSB) consumption and its effect on
underlying mechanisms of the nitric oxide pathway. APPROACH AND RESULTS: In a
randomized, single-blind, crossover trial, 12 healthy male participants consumed
600 mL (20 oz.) of water or a commercial SSB across 2 visits. Endothelial and
vascular smooth muscle functions were assessed in the microcirculation using
laser speckle contrast imaging coupled with iontophoresis and in the
macrocirculation using brachial artery ultrasound with flow- and nitrate-mediated
dilation. Compared with water, SSB consumption impaired microvascular and
macrovascular endothelial function as indicated by a decrease in the vascular
response to acetylcholine iontophoresis (208.3+/-24.3 versus 144.2+/-15.7%,
P<0.01) and reduced flow-mediated dilation (0.019+/-0.002 versus 0.014+/
0.002%/s, P<0.01), respectively. Systemic vascular smooth muscle remained
preserved. Similar decreases in endothelial function were observed during acute
hyperglycemia in an in vivo rat model. However, function was fully restored by
treatment with the antioxidants, N-acetylcysteine and apocynin. In addition, ex
vivo experiments revealed that although the production of reactive oxygen species
was increased during acute hyperglycemia, the bioavailability of nitric oxide in
the endothelium was decreased, despite no change in the activation state of
endothelial nitric oxide synthase. CONCLUSIONS: To our knowledge, this is the
first study to assess the vascular effects of acute hyperglycemia induced by
commercial SSB consumption alone. These findings suggest that SSB-mediated
endothelial dysfunction is partly due to increased oxidative stress that
decreases nitric oxide bioavailability. CLINICAL TRIAL REGISTRATION: URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366442&isReview=
rue. Australian New Zealand Clinical Trials Registry Number: ACTRN12614000614695.
PMID- 28408373
TI - Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol
and Particle Number: The Multi-Ethnic Study of Atherosclerosis.
AB - OBJECTIVE: The relationship between air pollution and cardiovascular disease may
be explained by changes in high-density lipoprotein (HDL). APPROACH AND RESULTS:
We examined the cross-sectional relationship between air pollution and both HDL
cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of
Atherosclerosis Air Pollution). Study participants were 6654 white, black,
Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual
residential ambient fine particulate pollution exposure (PM2.5) and black carbon
concentrations using a fine-scale likelihood-based spatiotemporal model and
cohort-specific monitoring. Exposure periods were averaged to 12 months, 3
months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number
were measured in the year 2000 using the cholesterol oxidase method and nuclear
magnetic resonance spectroscopy, respectively. We used multivariable linear
regression to examine the relationship between air pollution exposure and HDL
measures. A 0.7*10-6 m-1 higher exposure to black carbon (a marker of traffic
related pollution) averaged over a 1-year period was significantly associated
with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to
0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95%
confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5
MUg/m3 higher PM2.5 was associated with lower HDL particle number (-0.64 MUmol/L;
95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL;
95% confidence interval, -0.82 to 0.71). CONCLUSIONS: These data are consistent
with the hypothesis that exposure to air pollution is adversely associated with
measures of HDL.
PMID- 28408374
TI - Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental
Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial
Cells.
AB - OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies
complicated by fetal growth restriction (FGR). We used first trimester placental
samples from pregnancies with later small for gestational age (SGA) infants as a
surrogate for FGR. The functional consequences of reduced BGN and the downstream
targets of BGN were determined. Furthermore, the expression of targets was
validated in primary placental endothelial cells isolated from FGR or control
pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time
polymerase chain reaction in placental tissues collected during chorionic villous
sampling performed at 10 to 12 weeks' gestation from pregnancies that had known
clinical outcomes, including SGA. Short-interference RNA reduced BGN expression
in telomerase-immortalized microvascular endothelial cells, and the effect on
proliferation, angiogenesis, and thrombin generation was determined. An
angiogenesis array identified downstream targets of BGN, and their expression in
control and FGR primary placental endothelial cells was validated using real-time
polymerase chain reaction. Reduced BGN expression was observed in SGA placental
tissues. BGN reduction decreased network formation of telomerase-immortalized
microvascular endothelial cells but did not affect thrombin generation or
cellular proliferation. The array identified target genes, which were further
validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor alpha
(PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin
(ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif
chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells
and primary placental endothelial cells obtained from control and FGR
pregnancies. CONCLUSIONS: This study reports a temporal relationship between
altered placental BGN expression and subsequent development of SGA. Reduction of
BGN in vascular endothelial cells leads to disrupted network formation and
alterations in the expression of genes involved in angiogenesis. Therefore,
differential expression of these may contribute to aberrant angiogenesis in SGA
pregnancies.
PMID- 28408375
TI - Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via
Activating the NF-kappaB Signaling Pathway in HepG2 Cells.
AB - OBJECTIVE: Serum uric acid (UA) has been associated with increased risk of
cardiovascular and metabolic diseases. However, the causal mechanisms linking
elevated UA levels to cardio-metabolic diseases are still unsettled. One
potential explanation for how UA might contribute to cardio-metabolic disease
might be its ability to induce systemic inflammation. APPROACH AND RESULTS:
Herein, we report a positive relationship between serum UA and acute-phase
reactants, such as high-sensitivity C-reactive protein, fibrinogen, ferritin,
complement C3, and erythrocyte sedimentation rate, in a cohort of 2731
nondiabetic adults. The relationship remains significant after adjustment for
several confounders, including age, sex, adiposity, anti-hypertensive treatments
or diuretics use. To confirm the existence of a causal relationship, we examined
the effect of UA on the expression of inflammatory biomarkers in human hepatoma
HepG2 cells and characterized the signaling pathway by which UA acts. We show
that UA stimulates the expression of C-reactive protein, fibrinogen, ferritin,
and complement C3 in a dose-dependent fashion. The proinflammatory effects of UA
were abrogated by benzbromarone, a specific inhibitor of UA transporters.
Exposure of cells to UA resulted in activation of the IkappaB
kinase/IkappaBalpha/NF-kappaB signaling pathway that was attenuated by
benzbromarone. The effect of UA was completely blocked by the antioxidant N
acetylcysteine. CONCLUSIONS: These in vivo and in vitro data suggest that
hyperuricemia might induce the expression of hepatic inflammatory molecules by
activating the proinflammatory NF-kappaB signaling cascade. Because inflammation
has an important pathogenetic role in metabolic and cardiovascular disease, our
study may help understanding the mechanism by which hyperuricemia may contribute
to organ damage.
PMID- 28408376
TI - A comparative study of tissue-engineered constructs from Acropora and Porites
coral in a large animal bone defect model.
AB - OBJECTIVES: To compare the therapeutic potential of tissue-engineered constructs
(TECs) combining mesenchymal stem cells (MSCs) and coral granules from either
Acropora or Porites to repair large bone defects. MATERIALS AND METHODS: Bone
marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules
in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone
autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal
defects in sheep. Bimonthly radiographic follow-up was completed until killing
four months post-operatively. Explants were subsequently processed for microCT
and histology to assess bone formation and coral bioresorption. Statistical
analyses comprised Mann-Whitney, t-test and Kruskal-Wallis tests. Data were
expressed as mean and standard deviation. RESULTS: A two-fold increaseof newly
formed bone volume was observed for Acropora-TECs when compared with Porites-TECs
(14 sd 1089 mm3versus 782 sd 507 mm3; p = 0.09). Bone union was consistent with
autograft (1960 sd 518 mm3). The kinetics of bioresorption and bioresorption
rates at four months were different for Acropora-TECs and Porites-TECs (81% sd 5%
versus 94% sd 6%; p = 0.04). In comparing the defects that healed with those that
did not, we observed that, when major bioresorption of coral at two months occurs
and a scaffold material bioresorption rate superior to 90% at four months is
achieved, bone nonunion consistently occurred using coral-based TECs. DISCUSSION:
Bone regeneration in critical-size defects could be obtained with full
bioresorption of the scaffold using coral-based TECs in a large animal model. The
superior performance of Acropora-TECs brings us closer to a clinical application,
probably because of more suitable bioresorption kinetics. However, nonunion still
occurred in nearly half of the bone defects.Cite this article: A. Decambron, M.
Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V.
Viateau. A comparative study of tissue-engineered constructs from Acropora and
Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208-215.
DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1.
PMID- 28408377
TI - Focus on the person, not the problem.
PMID- 28408378
TI - NHS thrombectomy plan needs more doctors, say stroke experts.
PMID- 28408379
TI - "Obesity-Associated" Breast Cancer in Lean Women: Metabolism and Inflammation as
Critical Modifiers of Risk.
AB - Why is obesity only weakly associated with certain "obesity-driven" cancers?
Recent population studies identify cohorts of high body mass index (BMI) subjects
with unexpectedly reduced risk for breast and colon cancer, and normal BMI
subjects with unexpectedly elevated risk for breast cancer, provoking hard
thinking about cellular and molecular mechanisms that most strongly couple
obesity to cancer occurrence or progression. Emerging work suggests that abnormal
metabolism and its associated chronic inflammation make the difference. Type II
diabetes, for example, is a chronic inflammatory disease with specific imbalances
in T-cell and myeloid-origin cytokines. Inflammation is elevated systemically,
measured through blood biomarkers, and locally in adipose tissue. Here, cytokines
and chemokines likely modify tumor microenvironments in dangerous ways. High BMI
subjects with low inflammation and less disturbed metabolism appear to have
reduced risk for certain obesity-associated cancers, whereas lean or slightly
overweight subjects with high inflammation and metabolic abnormalities have
elevated risk. This latter phenotype is prevalent among South Asian adults and
suggests we are not monitoring certain normal weight adults sufficiently for
risks of "obesity-associated" cancers. Profiling of patient metabolism and
inflammation should accompany measures of body composition when considering
cancer risk; the evidence base for these refinements must be extended through
new, prospective observational studies. Cancer Prev Res; 10(5); 267-9. (c)2017
AACRSee related article by Iyengar et al., Cancer Prev Res 2017;10(4):235-43.
PMID- 28408380
TI - Independent board needed to promote research integrity, US panel says.
PMID- 28408381
TI - NHS may turn to private sources for cash boost.
PMID- 28408382
TI - Extending the spectrum of DNA sequences retrieved from ancient bones and teeth.
AB - The number of DNA fragments surviving in ancient bones and teeth is known to
decrease with fragment length. Recent genetic analyses of Middle Pleistocene
remains have shown that the recovery of extremely short fragments can prove
critical for successful retrieval of sequence information from particularly
degraded ancient biological material. Current sample preparation techniques,
however, are not optimized to recover DNA sequences from fragments shorter than
~35 base pairs (bp). Here, we show that much shorter DNA fragments are present in
ancient skeletal remains but lost during DNA extraction. We present a refined
silica-based DNA extraction method that not only enables efficient recovery of
molecules as short as 25 bp but also doubles the yield of sequences from longer
fragments due to improved recovery of molecules with single-strand breaks.
Furthermore, we present strategies for monitoring inefficiencies in library
preparation that may result from co-extraction of inhibitory substances during
DNA extraction. The combination of DNA extraction and library preparation
techniques described here substantially increases the yield of DNA sequences from
ancient remains and provides access to a yet unexploited source of highly
degraded DNA fragments. Our work may thus open the door for genetic analyses on
even older material.
PMID- 28408383
TI - Pioglitazone for the treatment of NASH in patients with prediabetes or type 2
diabetes mellitus.
PMID- 28408384
TI - Protective effects of Helicobacter pylori for IBD are related to the cagA
positive strain.
PMID- 28408385
TI - SENP1 activity sustains cancer stem cell in hypoxic HCC.
PMID- 28408387
TI - How to Improve Maintenance Intravenous Fluid Prescribing Practices in
Bronchiolitis.
PMID- 28408386
TI - Increased PD-1+ and TIM-3+ TILs during Cetuximab Therapy Inversely Correlate with
Response in Head and Neck Cancer Patients.
AB - Despite emerging appreciation for the important role of immune checkpoint
receptors in regulating the effector functions of T cells, it is unknown whether
their expression is involved in determining the clinical outcome in response to
cetuximab therapy. We examined the expression patterns of immune checkpoint
receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including
granzyme B and perforin) of CD8+ tumor-infiltrating lymphocytes (TIL) and
compared them with those of peripheral blood T lymphocytes (PBL) in patients with
head and neck cancer (HNSCC) during cetuximab therapy. The frequency of PD-1 and
TIM-3 expression was significantly increased in CD8+ TILs compared with CD8+ PBLs
(P = 0.008 and P = 0.02, respectively). This increased CD8+ TIL population
coexpressed granzyme B/perforin and PD-1/TIM-3, which suggests a regulatory role
for these immune checkpoint receptors in cetuximab-promoting cytolytic activities
of CD8+ TILs. Indeed, the increased frequency of PD-1+ and TIM-3+ CD8+ TILs was
inversely correlated with clinical outcome of cetuximab therapy. These findings
support the use of PD-1 and TIM-3 as biomarkers to reflect immune status of CD8+
T cells in the tumor microenvironment during cetuximab therapy. Blockade of these
immune checkpoint receptors might enhance cetuximab-based cancer immunotherapy to
reverse CD8+ TIL dysfunction, thus potentially improving clinical outcomes of
HNSCC patients. Cancer Immunol Res; 5(5); 408-16. (c)2017 AACR.
PMID- 28408388
TI - Hyponatremia and Hypotonic Intravenous Fluids Are Associated With Unfavorable
Outcomes of Bronchiolitis Admissions.
AB - OBJECTIVES: Hyponatremia has been associated with unfavorable outcomes when
present at admission in children with bronchiolitis. Delayed hyponatremia may be
a modifiable risk factor for severe disease that is influenced by intravenous
fluid (IVF) tonicity. We hypothesized that both hyponatremia and prescription of
severely hypotonic IVF are associated with unfavorable outcomes, and that
prescription of severely hypotonic IVF is associated with subsequent
hyponatremia. METHODS: Data were retrospectively extracted for 1557 pediatric
inpatients with bronchiolitis. Any day on which a subject was prescribed IVF with
sodium <70 mEq/L was termed "IVF <70." All other days on which IVF was prescribed
were termed "IVF >=70." Any blood sodium <=135 mEq/L defined hyponatremia for
that day. All other days with sodium available were labeled normonatremia.
Variables were compared with Spearman correlation, Wilcoxon rank test, or chi2.
Significant results had P < .05. RESULTS: Blood sodium levels correlated
negatively with hospital length of stay (r = -0.477, P < .0001). On each of the
first 4 days of hospitalization, significantly increased hospital length of stay
was observed in patients with hyponatremia (n = 134 [25.7% of subjects with
available sodium data]) versus patients with normonatremia (n = 387 [74.3%]), and
in patients prescribed IVF <70 (n = 348 [46.3% of subjects prescribed IVF])
versus patients prescribed IVF >=70 (n = 403 [53.7%]). Patients prescribed IVF
<70 had increased rates of hyponatremia on the subsequent day versus patients
prescribed IVF >=70 (50.0% vs 26.9%, P < .001). CONCLUSIONS: In children
hospitalized with bronchiolitis, hyponatremia may be a modifiable risk factor for
severe disease that may be mitigated by avoiding use of severely hypotonic IVF.
PMID- 28408389
TI - Bazedoxifene for HRT?
AB - Duavive (Pfizer) is a modified-release formulation of conjugated oestrogens plus
bazedoxifene acetate (a selective oestrogen receptor modulator). It is licensed
for treatment of oestrogen deficiency symptoms in postmenopausal women with a
uterus for whom treatment with progestogen-containing therapy is not
appropriate.1,2 It was licensed by the European Medicines Agency (EMA) in 2014
and launched in the UK in July 2016.1,3 Here, we review the evidence on efficacy
and safety of conjugated oestrogens/bazedoxifene and consider its place in the
management of symptoms associated with the menopause.
PMID- 28408390
TI - Lidocaine/prilocaine spray for premature ejaculation.
AB - Although premature ejaculation is the most common ejaculation problem, it is
poorly understood and currently has no standard definition.1 Typically, it
involves reduced time to ejaculation, inability to control or delay ejaculation
and associated distress.1-5 Treatments that have been assessed include
psychosexual counselling, antidepressants (e.g. selective serotonin reuptake
inhibitors), phosphodiesterase type-5 inhibitors, tramadol and topical
anaesthetic agents (e.g. lidocaine/prilocaine cream). A new formulation
(cutaneous spray) of lidocaine/prilocaine (Fortacin-Plethora Solutions Ltd.) was
launched in the UK in November 2016 for the treatment of primary premature
ejaculation.6,7 Here, we consider the evidence for lidocaine/prilocaine spray and
whether it has a role in the treatment of premature ejaculation.
PMID- 28408391
TI - LMNA-associated partial lipodystrophy: anticipation of metabolic complications.
AB - BACKGROUND: Type-2 familial partial lipodystrophy (FPLD2) is a rare autosomal
dominant lipodystrophic disorder due to mutations in LMNA encoding lamin A/C, a
key epigenetic regulator. FPLD2 severity is determined by the occurrence of
metabolic complications, especially diabetes and hypertriglyceridaemia. We
evaluated the disease history and severity over generations. METHODS: This
retrospective study of the largest cohort of patients with FPLD2 reported to date
investigates 85 patients from 24 families comprising three generations (G1: n=39;
G2: n=41; G3: n=5). RESULTS: Lipodystrophy appears with the same characteristics
and at the same age in first generation (G1;18.6+/-1.5 years) and second
generation (G2;15.9+/-0.8 years). Despite similar body mass index (23.7+/-0.6 vs
23.8+/-0.6 kg/m2), the mean delay between the onset of lipodystrophy and diabetes
was far shorter in G2 (10.5+/-2.4 years) than in G1 (29.0+/-3.5 years)
(p=0.0002). The same is true for the delay preceding hypertriglyceridaemia (G2:
4.5+/-1.4; G1: 19.3+/-3.2 years) (p=0.002), revealing an anticipation phenomenon.
Observations in G3, and analysis within each family of disease history and
diagnostic procedures, confirmed this result. CONCLUSIONS: This study is a rare
example of anticipation unrelated to a trinucleotide expansion. Discovery of this
early occurrence of metabolic complications in young generations underlines the
utility of presymptomatic genetic diagnosis, with careful metabolic screening and
preventive lifestyle in all at-risk individuals.
PMID- 28408394
TI - A close-up look at the spliceosome, at last.
AB - Major developments in cryo-electron microscopy in the past three or four years
have led to the solution of a number of spliceosome structures at high
resolution, e.g., the fully assembled but not yet active spliceosome (Bact), the
spliceosome just after the first step of splicing (C), and the spliceosome
activated for the second step (C*). Therefore 30 years of genetics and
biochemistry of the spliceosome can now be interpreted at the structural level. I
have closely examined the RNase H domain of Prp8 in each of the structures.
Interestingly, the RNase H domain has different and unexpected roles in each of
the catalytic steps of splicing.
PMID- 28408395
TI - High-throughput, low-loss, low-cost, and label-free cell separation using
electrophysiology-activated cell enrichment.
AB - Currently, cell separation occurs almost exclusively by density gradient methods
and by fluorescence- and magnetic-activated cell sorting (FACS/MACS). These
variously suffer from lack of specificity, high cell loss, use of labels, and
high capital/operating cost. We present a dielectrophoresis (DEP)-based cell
separation method, using 3D electrodes on a low-cost disposable chip; one cell
type is allowed to pass through the chip whereas the other is retained and
subsequently recovered. The method advances usability and throughput of DEP
separation by orders of magnitude in throughput, efficiency, purity, recovery
(cells arriving in the correct output fraction), cell losses (those which are
unaccounted for at the end of the separation), and cost. The system was evaluated
using three example separations: live and dead yeast; human cancer cells/red
blood cells; and rodent fibroblasts/red blood cells. A single-pass protocol can
enrich cells with cell recovery of up to 91.3% at over 300,000 cells per second
with >3% cell loss. A two-pass protocol can process 300,000,000 cells in under 30
min, with cell recovery of up to 96.4% and cell losses below 5%, an effective
processing rate >160,000 cells per second. A three-step protocol is shown to be
effective for removal of 99.1% of RBCs spiked with 1% cancer cells while
maintaining a processing rate of ~170,000 cells per second. Furthermore, the self
contained and low-cost nature of the separator device means that it has potential
application in low-contamination applications such as cell therapies, where good
manufacturing practice compatibility is of paramount importance.
PMID- 28408396
TI - Novel role of immature myeloid cells in formation of new lymphatic vessels
associated with inflammation and tumors.
AB - Inflammation triggers an immune cell-driven program committed to restoring
homeostasis to injured tissue. Central to this process is vasculature
restoration, which includes both blood and lymphatic networks. Generation of new
vessels or remodeling of existing vessels are also important steps in metastasis
the major cause of death for cancer patients. Although roles of the lymphatic
system in regulation of inflammation and cancer metastasis are firmly
established, the mechanisms underlying the formation of new lymphatic vessels
remain a subject of debate. Until recently, generation of new lymphatics in
adults was thought to occur exclusively through sprouting of existing vessels
without help from recruited progenitors. However, emerging findings from clinical
and experimental studies show that lymphoendothelial progenitors, particularly
those derived from immature myeloid cells, play an important role in this
process. This review summarizes current evidence for the existence and
significant roles of myeloid-derived lymphatic endothelial cell progenitors (M
LECPs) in generation of new lymphatics. We describe specific markers of M-LECPs
and discuss their biologic behavior in culture and in vivo, as well as currently
known molecular mechanisms of myeloid-lymphatic transition (MLT). We also discuss
the implications of M-LECPs for promoting adaptive immunity, as well as cancer
metastasis. We conclude that improved mechanistic understanding of M-LECP
differentiation and its role in adult lymphangiogenesis may lead to new
therapeutic approaches for correcting lymphatic insufficiency or excessive
formation of lymphatic vessels in human disorders.
PMID- 28408397
TI - The IL-31/IL-31 receptor axis: general features and role in tumor
microenvironment.
AB - IL-31 is a recently identified cytokine with a well-defined role in the
pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33,
binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and
the shared oncostatin M R. Signaling through the IL-31R involves the MAPK,
PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with
different signaling activities have been identified. IL-31 is produced
predominantly by circulating Th2 lymphocytes and skin-homing CLA+CD45RO+ T cells.
Studies in humans have demonstrated a pathogenic role for IL-31 in atopic
dermatitis and allergic asthma. The first demonstration of the involvement of the
IL-31/IL-31R axis in cancer came from studies in patients with mycosis
fungoides/Sezary syndrome, the most frequent, cutaneous T cell lymphoma. Tumor
cells were shown to produce IL-31, whose serum levels correlated with pruritus
intensity. Follicular lymphoma (FL) B cells and their counterparts-germinal
center B cells-produced IL-31 and expressed IL-31R, which signaled in the former,
but not the latter, cells. IL-31 released in association with microvesicles
promoted tumor growth through autocrine/paracrine loops. Malignant mast cells
from patients with mastocytosis or Philadelphia-negative myeloproliferative
disorder produced IL-31, which contributed to pruritus pathogenesis. Finally,
patients with endometrial carcinoma displayed high serum levels of IL-31 and IL
33, which may represent promising disease biomarkers. Targeting strategies for
the IL-31/IL-31R axis have been developed, including the CIMM331 humanized anti
human IL-31RA antibody recently tested in a phase I/Ib study.
PMID- 28408398
TI - NHS trusts continue to think they are over-regulated, survey finds.
PMID- 28408399
TI - Demonstration of sympathetic nerve innervation in a patient with takotsubo
cardiomyopathy using single-photon emission CT.
PMID- 28408400
TI - Epigenetic Identity in AML Depends on Disruption of Nonpromoter Regulatory
Elements and Is Affected by Antagonistic Effects of Mutations in Epigenetic
Modifiers.
AB - We performed cytosine methylation sequencing on genetically diverse patients with
acute myeloid leukemia (AML) and found leukemic DNA methylation patterning is
primarily driven by nonpromoter regulatory elements and CpG shores. Enhancers
displayed stronger differential methylation than promoters, consisting
predominantly of hypomethylation. AMLs with dominant hypermethylation featured
greater epigenetic disruption of promoters, whereas those with dominant
hypomethylation displayed greater disruption of distal and intronic regions.
Mutations in IDH and DNMT3A had opposing and mutually exclusive effects on the
epigenome. Notably, co-occurrence of both mutations resulted in epigenetic
antagonism, with most CpGs affected by either mutation alone no longer affected
in double-mutant AMLs. Importantly, this epigenetic antagonism precedes malignant
transformation and can be observed in preleukemic LSK cells from Idh2R140Q or
Dnmt3aR882H single-mutant and Idh2R140Q/Dnmt3aR882H double-mutant mice. Notably,
IDH/DNMT3A double-mutant AMLs manifested upregulation of a RAS signaling
signature and displayed unique sensitivity to MEK inhibition ex vivo as compared
with AMLs with either single mutation.Significance: AML is biologically
heterogeneous with subtypes characterized by specific genetic and epigenetic
abnormalities. Comprehensive DNA methylation profiling revealed that differential
methylation of nonpromoter regulatory elements is a driver of epigenetic
identity, that gene mutations can be context-dependent, and that co-occurrence of
mutations in epigenetic modifiers can result in epigenetic antagonism. Cancer
Discov; 7(8); 868-83. (c)2017 AACR.This article is highlighted in the In This
Issue feature, p. 783.
PMID- 28408401
TI - Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone
Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
AB - Effective therapies for non-small cell lung cancer (NSCLC) remain challenging
despite an increasingly comprehensive understanding of somatically altered
oncogenic pathways. It is now clear that therapeutic agents with potential to
impact the tumor immune microenvironment potentiate immune-orchestrated
therapeutic benefit. Herein, we evaluated the immunoregulatory properties of
histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that
modulate the epigenome, with a focus on key cell subsets that are engaged in an
immune response. By evaluating human peripheral blood and NSCLC tumors, we show
that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that
support enhanced T-cell activation and improved function of antigen-presenting
cells. The bromodomain inhibitor JQ1 attenuated CD4+FOXP3+ T regulatory cell
suppressive function and synergized with ricolinostat to facilitate immune
mediated tumor growth arrest, leading to prolonged survival of mice with lung
adenocarcinomas. Collectively, our findings highlight the immunomodulatory
effects of two epigenetic modifiers that, together, promote T cell-mediated
antitumor immunity and demonstrate their therapeutic potential for treatment of
NSCLC.Significance: Selective inhibition of HDACs and bromodomain proteins
modulates tumor-associated immune cells in a manner that favors improved T-cell
function and reduced inhibitory cellular mechanisms. These effects facilitated
robust antitumor responses in tumor-bearing mice, demonstrating the therapeutic
potential of combining these epigenetic modulators for the treatment of NSCLC.
Cancer Discov; 7(8); 852-67. (c)2017 AACR.This article is highlighted in the In
This Issue feature, p. 783.
PMID- 28408403
TI - Antonina Roll-Mecak: Decoding the secrets of tubulin complexity.
AB - Antonina Roll-Mecak studies how tubulin variability modulates the specificity,
complexity, and function of the microtubule network.
PMID- 28408402
TI - Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat
expression to the asymptomatic phase of ALS/FTD.
AB - The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral
sclerosis and frontotemporal dementia (c9ALS/FTD). Non-conventional repeat
translation results in five dipeptide repeat proteins (DPRs), but their clinical
utility, overall significance, and temporal course in the pathogenesis of
c9ALS/FTD are unclear, although animal models support a gain-of-function
mechanism. Here, we established a poly-GP immunoassay from cerebrospinal fluid
(CSF) to identify and characterize C9orf72 patients. Significant poly-GP levels
were already detectable in asymptomatic C9orf72 mutation carriers compared to
healthy controls and patients with other neurodegenerative diseases. The poly-GP
levels in asymptomatic carriers were similar to symptomatic c9ALS/FTD cases. Poly
GP levels were not correlated with disease onset, clinical scores, and CSF levels
of neurofilaments as a marker for axonal damage. Poly-GP determination in CSF
revealed a C9orf72 mutation carrier in our cohort and may thus be used as a
diagnostic marker in addition to genetic testing to screen patients.
Presymptomatic expression of poly-GP and likely other DPR species may contribute
to disease onset and thus represents an alluring therapeutic target.
PMID- 28408405
TI - Communicating Science through a Novel Type of Journal.
PMID- 28408404
TI - Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and
degradation.
AB - Integrin activation is an indispensable step for various integrin-mediated
biological functions. Kindlin-2 is known to coactivate integrins with Talin;
however, molecules that restrict integrin activation are elusive. Here, we
demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2
protein in cells and hinders integrin activation. Smurf1 interacts with and
promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates
degradation of Kindlin-2 but not Talin, leading to inhibition of alphaIIbbeta3
integrin activation in Chinese hamster ovary cells and beta1 integrin activation
in fibroblasts. Enhanced activation of beta1 integrin was found in Smurf1
knockout mouse embryonic fibroblasts, which correlates with an increase in
Kindlin-2 protein levels. Similarly, a reciprocal relationship between Smurf1 and
Kindlin-2 protein levels is found in tissues from colon cancer patients,
suggesting that Smurf1 mediates Kindlin-2 degradation in vivo. Collectively, we
demonstrate that Smurf1 acts as a brake for integrin activation by controlling
Kindlin-2 protein levels, a new mechanism that permits precise modulation of
integrin-mediated cellular functions.
PMID- 28408406
TI - A Problem-Sorting Task Detects Changes in Undergraduate Biological Expertise over
a Single Semester.
AB - Calls for undergraduate biology reform share similar goals: to produce people who
can organize, use, connect, and communicate about biological knowledge. Achieving
these goals requires students to gain disciplinary expertise. Experts organize,
access, and apply disciplinary knowledge differently than novices, and expertise
is measurable. By asking introductory biology students to sort biological
problems, we investigated whether they changed how they organized and linked
biological ideas over one semester of introductory biology. We administered the
Biology Card Sorting Task to 751 students enrolled in their first or second
introductory biology course focusing on either cellular-molecular or organismal
population topics, under structured or unstructured sorting conditions. Students
used a combination of superficial, deep, and yet-uncharacterized ways of
organizing and connecting biological knowledge. In some cases, this translated to
more expert-like ways of organizing knowledge over a single semester, best
predicted by whether students were enrolled in their first or second semester of
biology and by the sorting condition completed. In addition to illuminating
differences between novices and experts, our results show that card sorting is a
robust way of detecting changes in novices' biological expertise-even in
heterogeneous populations of novice biology students over the time span of a
single semester.
PMID- 28408407
TI - Using Next-Generation Sequencing to Explore Genetics and Race in the High School
Classroom.
AB - With the development of new sequencing and bioinformatics technologies, concepts
relating to personal genomics play an increasingly important role in our society.
To promote interest and understanding of sequencing and bioinformatics in the
high school classroom, we developed and implemented a laboratory-based teaching
module called "The Genetics of Race." This module uses the topic of race to
engage students with sequencing and genetics. In the experimental portion of this
module, students isolate their own mitochondrial DNA using standard biotechnology
techniques and collect next-generation sequencing data to determine which of
their classmates are most and least genetically similar to themselves. We
evaluated the efficacy of this module by administering a pretest/posttest
evaluation to measure student knowledge related to sequencing and bioinformatics,
and we also conducted a survey at the conclusion of the module to assess student
attitudes. Upon completion of our Genetics of Race module, students demonstrated
significant learning gains, with lower-performing students obtaining the highest
gains, and developed more positive attitudes toward scientific research.
PMID- 28408408
TI - Students' Use of Optional Online Reviews and Its Relationship to Summative
Assessment Outcomes in Introductory Biology.
AB - Retrieval practice has been shown to produce significant enhancements in student
learning of course information, but the extent to which students make use of
retrieval to learn information on their own is unclear. In the current study,
students in a large introductory biology course were provided with optional
online review questions that could be accessed as Test questions (requiring
students to answer the questions before receiving feedback) or as Read questions
(providing students with the question and correct answer up-front). Students more
often chose to access the questions as Test compared with Read, and students who
used the Test questions scored significantly higher on subsequent exams compared
with students who used Read questions or did not access the questions at all.
Following an in-class presentation of superior exam performance following use of
the Test questions, student use of Test questions increased significantly for the
remainder of the term. These results suggest that practice questions can be an
effective tool for enhancing student achievement in biology and that informing
students about performance-based outcomes coincides with increased use of
retrieval practice.
PMID- 28408409
TI - Broadening Participation in the Sciences within and from Africa: Purpose,
Challenges, and Prospects.
AB - Many of Africa's challenges have scientific solutions, but there are fewer
individuals engaged in scientific activity per capita on this continent than on
any other. Only a handful of African scientists use their skills to capacity or
are leaders in their disciplines. Underrepresentation of Africans in scientific
practice, discourse, and decision making reduces the richness of intellectual
contributions toward hard problems worldwide. This essay outlines challenges
faced by teacher-scholars from sub-Saharan Africa as we build scientific
expertise. Access to tertiary-level science is difficult and uneven across
Africa, and the quality of training available varies from top-range to
inadequate. Access to science higher education needs to increase, particularly
for female students, first-generation literates, and rural populations. We make
suggestions for collaborative initiatives involving stakeholders outside Africa
and/or outside academia that could extend educational opportunities available to
African students and increase the chance that Africa-based expertise is globally
available.
PMID- 28408410
TI - Decreased cohesin in the brain leads to defective synapse development and anxiety
related behavior.
AB - Abnormal epigenetic regulation can cause the nervous system to develop
abnormally. Here, we sought to understand the mechanism by which this occurs by
investigating the protein complex cohesin, which is considered to regulate gene
expression and, when defective, is associated with higher-level brain dysfunction
and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated
conditional Smc3-knockout mice and observed greater dendritic complexity and
larger numbers of immature synapses in the cerebral cortex of Smc3+/- mice.
Smc3+/- mice also exhibited more anxiety-related behavior, which is a symptom of
CdLS. Further, a gene ontology analysis after RNA-sequencing suggested the
enrichment of immune processes, particularly the response to interferons, in the
Smc3+/- mice. Indeed, fewer synapses formed in their cortical neurons, and this
phenotype was rescued by STAT1 knockdown. Thus, low levels of cohesin expression
in the developing brain lead to changes in gene expression that in turn lead to a
specific and abnormal neuronal and behavioral phenotype.
PMID- 28408411
TI - Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned
Responding.
AB - Patients with anxiety disorders often experience a relapse in symptoms after
exposure therapy. Similarly, threat responses acquired during Pavlovian threat
conditioning often return after extinction learning. Accordingly, there is a need
for alternative methods to persistently reduce threat responding. Studies in
rodents have suggested that exercising behavioral control over an aversive
stimulus can persistently diminish threat responses, and that these effects are
mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this
fMRI study, we attempted to translate these findings to humans. Subjects first
underwent threat conditioning. We then contrasted two forms of safety learning:
active avoidance, in which participants could prevent the shock through an
action, and yoked extinction, with shock presentation matched to the active
condition, but without instrumental control. The following day, we assessed
subjects' threat responses (measured by skin conductance) to the conditioned
stimuli without shock. Subjects next underwent threat conditioning with novel
stimuli. Yoked extinction subjects showed an increase in conditioned response to
stimuli from the previous day, but the active avoidance group did not.
Additionally, active avoidance subjects showed reduced conditioned responding
during novel threat conditioning, but the extinction group did not. We observed
between-group differences in striatal BOLD responses to shock omission in
Avoidance/Extinction. These findings suggest a differential role for the striatum
in human active avoidance versus extinction learning, and indicate that active
avoidance may be more effective than extinction in persistently diminishing
threat responses.SIGNIFICANCE STATEMENT Extinguished threat responses often
reemerge with time, highlighting the importance of identifying more enduring
means of attenuation. We compared the effects of active avoidance learning and
yoked extinction on threat responses in humans and contrasted the neural
circuitry engaged by these two processes. Subjects who learned to prevent a shock
through an action maintained low threat responses after safety learning and
showed attenuated threat conditioning with novel stimuli, in contrast to those
who underwent yoked extinction. The results suggest that experiences of active
control over threat engage the striatum and promote a shift from expression of
innate defensive responses toward more adaptive behavioral responses to
threatening stimuli.
PMID- 28408412
TI - Fluid Intelligence Predicts Novel Rule Implementation in a Distributed
Frontoparietal Control Network.
AB - Fluid intelligence has been associated with a distributed cognitive control or
multiple-demand (MD) network, comprising regions of lateral frontal, insular,
dorsomedial frontal, and parietal cortex. Human fluid intelligence is also
intimately linked to task complexity, and the process of solving complex problems
in a sequence of simpler, more focused parts. Here, a complex target detection
task included multiple independent rules, applied one at a time in successive
task epochs. Although only one rule was applied at a time, increasing task
complexity (i.e., the number of rules) impaired performance in participants of
lower fluid intelligence. Accompanying this loss of performance was reduced
response to rule-critical events across the distributed MD network. The results
link fluid intelligence and MD function to a process of attentional focus on the
successive parts of complex behavior.SIGNIFICANCE STATEMENT Fluid intelligence is
intimately linked to the ability to structure complex problems in a sequence of
simpler, more focused parts. We examine the basis for this link in the functions
of a distributed frontoparietal or multiple-demand (MD) network. With increased
task complexity, participants of lower fluid intelligence showed reduced
responses to task-critical events. Reduced responses in the MD system were
accompanied by impaired behavioral performance. Low fluid intelligence is linked
to poor foregrounding of task-critical information across a distributed MD
system.
PMID- 28408413
TI - Distinct Physiological Maturation of Parvalbumin-Positive Neuron Subtypes in
Mouse Prefrontal Cortex.
AB - Parvalbumin-positive (PV+) neurons control the timing of pyramidal cell output in
cortical neuron networks. In the prefrontal cortex (PFC), PV+ neuron activity is
involved in cognitive function, suggesting that PV+ neuron maturation is critical
for cognitive development. The two major PV+ neuron subtypes found in the PFC,
chandelier cells (ChCs) and basket cells (BCs), are thought to play different
roles in cortical circuits, but the trajectories of their physiological
maturation have not been compared. Using two separate mouse lines, we found that
in the mature PFC, both ChCs and BCs are abundant in superficial layer 2, but
only BCs are present in deeper laminar locations. This distinctive laminar
distribution was observed by postnatal day 12 (P12), when we first identified
ChCs by the presence of axon cartridges. Electrophysiology analysis of excitatory
synapse development, starting at P12, showed that excitatory drive remains low
throughout development in ChCs, but increases rapidly before puberty in BCs, with
an earlier time course in deeper-layer BCs. Consistent with a role of excitatory
synaptic drive in the maturation of PV+ neuron firing properties, the fast
spiking phenotype showed different maturation trajectories between ChCs and BCs,
and between superficial versus deep-layer BCs. ChC and BC maturation was nearly
completed, via different trajectories, before the onset of puberty. These
findings suggest that ChC and BC maturation may contribute differentially to the
emergence of cognitive function, primarily during prepubertal
development.SIGNIFICANCE STATEMENT Parvalbumin-positive (PV+) neurons tightly
control pyramidal cell output. Thus PV+ neuron maturation in the prefrontal
cortex (PFC) is crucial for cognitive development. However, the relative
physiological maturation of the two major subtypes of PV+ neurons, chandelier
cells (ChCs) and basket cells (BCs), has not been determined. We assessed the
maturation of ChCs and BCs in different layers of the mouse PFC, and found that,
from early postnatal age, ChCs and BCs differ in laminar location. Excitatory
synapses and fast-spiking properties matured before the onset of puberty in both
cell types, but following cell type-specific developmental trajectories. Hence,
the physiological maturation of ChCs and BCs may contribute to the emergence of
cognitive function differentially, and predominantly during prepubertal
development.
PMID- 28408414
TI - Posterior Parietal Cortex Guides Visual Decisions in Rats.
AB - Neurons in putative decision-making structures can reflect both sensory and
decision signals, making their causal role in decisions unclear. Here, we tested
whether rat posterior parietal cortex (PPC) is causal for processing visual
sensory signals or instead for accumulating evidence for decision alternatives.
We disrupted PPC activity optogenetically during decision making and compared
effects on decisions guided by auditory versus visual evidence. Deficits were
largely restricted to visual decisions. To further test for visual dominance in
PPC, we evaluated electrophysiological responses after individual sensory events
and observed much larger response modulation after visual stimuli than auditory
stimuli. Finally, we measured trial-to-trial spike count variability during
stimulus presentation and decision formation. Variability decreased sharply,
suggesting that the network is stabilized by inputs, unlike what would be
expected if sensory signals were locally accumulated. Our findings suggest that
PPC plays a causal role in processing visual signals that are accumulated
elsewhere.SIGNIFICANCE STATEMENT Defining the neural circuits that support
decision making bridges a gap between our understanding of simple sensorimotor
reflexes and our understanding of truly complex behavior. However, identifying
brain areas that play a causal role in decision making has proved challenging. We
tested the causal role of a candidate component of decision circuits, the rat
posterior parietal cortex (PPC). Our interpretation of the data benefited from
our use of animals trained to make decisions guided by either visual or auditory
evidence. Our results suggest that PPC plays a causal role specifically in visual
decision making and may support sensory aspects of the decision, such as
interpreting the visual signals so that evidence for a decision can be
accumulated elsewhere.
PMID- 28408416
TI - Alternative surgical training model will be trialled from 2018.
PMID- 28408415
TI - Impact of International Quality Improvement Collaborative on Congenital Heart
Surgery in Pakistan.
AB - BACKGROUND: The International Quality Improvement Collaborative (IQIC) was formed
to reduce mortality and morbidity from congenital heart disease (CHD) surgeries
in low/middle-income countries. OBJECTIVES: We conducted this study to compare
the postoperative outcomes of CHD surgeries at a centre in Pakistan before and
after joining IQIC. METHODS: The IQIC provides guidelines targeting key drivers
responsible for morbidity and mortality in postoperativepatients with CHD. We
focused primarily on nurse empowerment and improving the infection control
strategies at our centre. Patients with CHD who underwent surgery at this site
during the period 2011-2012 (pre-IQIC) were comparedwith those getting surgery in
2013-2014 (post-IQIC). Morbidity (major infections), mortality and factors
associated with them were assessed. RESULTS: There was a significant decrease in
surgical site infections and bacterial sepsis in the post-IQIC versus pre-IQIC
period (1% vs 30%, p=0.0001, respectively). A statistically insignificant
decrease in the mortality rate was also noted in post-IQIC versus pre-IQIC period
(6% vs 9%, p=0.17, respectively). Durations of ventilation and intensive care
unit (ICU) and hospital stay were significantly reduced in the post-IQIC period.
Age <1 year, malnutrition, low preoperative oxygen perfusion, Risk Adjustment for
Congenital Heart Surgery score >3, major chromosomal anomalies, perfusion-related
event, longer ventilation and ICU/hospital stay durations were associated with
greater odds of morbidity and mortality. CONCLUSION: Enrolling in the IQIC
programme was associated with an improvement in the postsurgical outcomes of the
CHD surgeries at our centre.
PMID- 28408417
TI - Breaking bad...proteins.
PMID- 28408418
TI - HSC niche: ample room for every guest stem cell.
PMID- 28408419
TI - The yin and yang of autophagy in AL amyloidosis.
PMID- 28408420
TI - HIV multicentric Castleman: rituximab sans maintenance.
PMID- 28408421
TI - Modeling CBL activating mutations in vivo.
PMID- 28408422
TI - Stopping bleeding is not enough to FIX hemarthropathy.
PMID- 28408424
TI - Plasmacytoid lymphocytes: a clue to dengue diagnosis.
PMID- 28408423
TI - Improving transplantation for IL2RG/JAK3 SCID.
PMID- 28408426
TI - Staffas A, Burgos da Silva M, van den Brink MRM. The intestinal microbiota in
allogeneic hematopoietic cell transplant and graft-versus-host disease. Blood.
2017;129(8):927-933.
PMID- 28408425
TI - IgD kappa multiple myeloma and myelodysplastic syndrome.
PMID- 28408427
TI - Marks DI, Rowntree C. Management of adults with T-cell lymphoblastic leukemia.
Blood. 2017;129(9):1134-1142.
PMID- 28408428
TI - Risitano AM, Ricklin D, Huang Y, et al. Peptide inhibitors of C3 activation as a
novel strategy of complement inhibition for the treatment of paroxysmal nocturnal
hemoglobinuria. Blood. 2014;123(13):2094-2101.
PMID- 28408430
TI - The lysosome: a crucial hub for AMPK and mTORC1 signalling.
AB - Much attention has recently been focussed on the lysosome as a signalling hub.
Following the initial discovery that localisation of the nutrient-sensitive
kinase, mammalian target of rapamycin complex 1 (mTORC1), to the lysosome was
essential for mTORC1 activation, the field has rapidly expanded to reveal the
role of the lysosome as a platform permitting the co-ordination of several
homeostatic signalling pathways. Much is now understood about how the lysosome
contributes to amino acid sensing by mTORC1, the involvement of the energy
sensing kinase, AMP-activated protein kinase (AMPK), at the lysosome and how both
AMPK and mTORC1 signalling pathways feedback to lysosomal biogenesis and
regeneration following autophagy. This review will cover the classical role of
the lysosome in autophagy, the dynamic signalling interactions which take place
on the lysosomal surface and the multiple levels of cross-talk which exist
between lysosomes, AMPK and mTORC1.
PMID- 28408429
TI - Ubiquitin and Parkinson's disease through the looking glass of genetics.
AB - Biochemical alterations found in the brains of Parkinson's disease (PD) patients
indicate that cellular stress is a major driver of dopaminergic neuronal loss.
Oxidative stress, mitochondrial dysfunction, and ER stress lead to impairment of
the homeostatic regulation of protein quality control pathways with a consequent
increase in protein misfolding and aggregation and failure of the protein
degradation machinery. Ubiquitin signalling plays a central role in protein
quality control; however, prior to genetic advances, the detailed mechanisms of
how impairment in the ubiquitin system was linked to PD remained mysterious. The
discovery of mutations in the alpha-synuclein gene, which encodes the main
protein misfolded in PD aggregates, together with mutations in genes encoding
ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin,
and FBX07, has provided an opportunity to dissect out the molecular basis of
ubiquitin signalling disruption in PD, and this knowledge will be critical for
developing novel therapeutic strategies in PD that target the ubiquitin system.
PMID- 28408431
TI - Molecular basis for the interaction between stress-inducible phosphoprotein 1
(STIP1) and S100A1.
AB - Stress-inducible phosphoprotein 1 (STIP1) is a cellular co-chaperone, which
regulates heat-shock protein 70 (Hsp70) and Hsp90 activity during client protein
folding. Members of the S100 family of dimeric calcium-binding proteins have been
found to inhibit Hsp association with STIP1 through binding of STIP1
tetratricopeptide repeat (TPR) domains, possibly regulating the chaperone cycle.
Here, we investigated the molecular basis of S100A1 binding to STIP1. We show
that three S100A1 dimers associate with one molecule of STIP1 in a calcium
dependent manner. Isothermal titration calorimetry revealed that individual STIP1
TPR domains, TPR1, TPR2A and TPR2B, bind a single S100A1 dimer with significantly
different affinities and that the TPR2B domain possesses the highest affinity for
S100A1. S100A1 bound each TPR domain through a common binding interface composed
of alpha-helices III and IV of each S100A1 subunit, which is only accessible
following a large conformational change in S100A1 upon calcium binding. The TPR2B
binding site for S100A1 was predominately mapped to the C-terminal alpha-helix of
TPR2B, where it is inserted into the hydrophobic cleft of an S100A1 dimer,
suggesting a novel binding mechanism. Our data present the structural basis
behind STIP1 and S100A1 complex formation, and provide novel insights into TPR
module-containing proteins and S100 family member complexes.
PMID- 28408432
TI - 1,N6-alpha-hydroxypropanoadenine, the acrolein adduct to adenine, is a substrate
for AlkB dioxygenase.
AB - 1,N6-alpha-hydroxypropanoadenine (HPA) is an exocyclic DNA adduct of acrolein -
an environmental pollutant and endocellular oxidative stress product. Escherichia
coli AlkB dioxygenase belongs to the superfamily of alpha-ketoglutarate (alphaKG)
and iron-dependent dioxygenases which remove alkyl lesions from bases via an
oxidative mechanism, thereby restoring native DNA structure. Here, we provide in
vivo and in vitro evidence that HPA is mutagenic and is effectively repaired by
AlkB dioxygenase. HPA generated in plasmid DNA caused A -> C and A -> T
transversions and, less frequently, A -> G transitions. The lesion was
efficiently repaired by purified AlkB protein; the optimal pH, Fe(II), and
alphaKG concentrations for this reaction were determined. In vitro kinetic data
show that the protonated form of HPA is preferentially repaired by AlkB, albeit
the reaction is stereoselective. Moreover, the number of reaction cycles carried
out by an AlkB molecule remains limited. Molecular modeling of the T(HPA)T/AlkB
complex demonstrated that the R stereoisomer in the equatorial conformation of
the HPA hydroxyl group is strongly preferred, while the S stereoisomer seems to
be susceptible to AlkB-directed oxidative hydroxylation only when HPA adopts the
syn conformation around the glycosidic bond. In addition to the biochemical
activity assays, substrate binding to the protein was monitored by differential
scanning fluorimetry allowing identification of the active protein form, with
cofactor and cosubstrate bound, and monitoring of substrate binding. In contrast
FTO, a human AlkB homolog, failed to bind an ssDNA trimer carrying HPA.
PMID- 28408433
TI - The relationship between circulating irisin levels and tissues AGE accumulation
in type 2 diabetes patients.
AB - Advanced glycation end-products (AGEs), measured by skin autofluorescence (AF),
are a factor in the development or worsening of many degenerative diseases, such
as diabetes and atherosclerosis. Irisin levels have been associated with
diabetes, endothelial dysfunction and atherosclerosis. The objective of the
present study was to investigate whether circulating irisin levels are correlated
with skin AF values in type 2 diabetes patients. A total of 362 Chinese type 2
diabetic patients and 100 age- and sex-matched healthy controls were recruited in
the present study. Clinical characteristics, blood biochemistry and circulating
irisin levels were measured. Skin AF was measured using an AGE reader.
Circulating irisin levels were significantly lower, while skin AF values were
increased in type 2 diabetes compared with controls (P<0.05 respectively). By
dividing the distribution of skin AF values into tertiles, serum irisin levels
gradually lowered with increasing skin AF values (P<0.05). After adjusting for
covariates, multivariate stepwise regression analysis demonstrated that serum
lower irisin levels were independently associated with skin AF (P=0.009).
Circulating irisin levels were lower in type 2 diabetes patients compared with
healthy controls. Lower levels of irisin are independently associated with
elevated skin AF values, indicating that circulating irisin levels could be
associated with AGEs accumulation, which is one of the reasons causing vascular
complications in diabetic patients.
PMID- 28408434
TI - Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With
Uncomplicated Type 1 Diabetes.
AB - Higher plasma uric acid (PUA) levels are associated with lower glomerular
filtration rate (GFR) and higher blood pressure (BP) in patients with type 1
diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and
vascular function in patients with uncomplicated T1D. T1D patients (n = 49) were
studied under euglycemic and hyperglycemic conditions at baseline and after PUA
lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied
under normoglycemic conditions (n = 24). PUA, GFR (inulin), effective renal
plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion
of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system
[RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow
mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric
oxide (NO), and inflammatory markers were measured before and after FBX
treatment. Gomez equations were used to estimate arteriolar afferent resistance,
efferent resistance (RE), and glomerular hydrostatic pressure (PGLO). FBX had a
modest systolic BP-lowering effect in T1D patients (112 +/- 10 to 109 +/- 9 mmHg,
P = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced
the filtration fraction response to hyperglycemia in T1D patients through larger
increases in RE, PGLO, and interleukin-18 but without impacting the RAAS. FBX
lowered systolic BP and modulated the renal RE responses to hyperglycemia but
without impacting the RAAS or NO levels, suggesting that PUA may augment other
hemodynamic or inflammatory mechanisms that control the renal response to
hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine
cardiorenal outcomes of PUA lowering in patients with T1D.
PMID- 28408435
TI - Neurturin and a GLP-1 Analogue Act Synergistically to Alleviate Diabetes in
Zucker Diabetic Fatty Rats.
AB - Neurturin (NRTN), a member of the glial-derived neurotrophic factor family, was
identified from an embryonic chicken pancreatic cDNA library in a screen for
secreted factors. In this study, we assessed the potential antidiabetic
activities of NRTN relative to liraglutide, a glucagon-like peptide 1 receptor
agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN
to 8-week-old male ZDF rats prevented the development of hyperglycemia and
improved metabolic parameters similar to liraglutide. NRTN treatment increased
pancreatic insulin content and beta-cell mass and prevented deterioration of
islet organization. However, unlike liraglutide-treated rats, NRTN-mediated
improvements were not associated with reduced body weight or food intake. Acute
NRTN treatment did not activate c-Fos expression in key feeding behavior and
metabolic centers in ZDF rat brain or directly enhance glucose-stimulated insulin
secretion from pancreatic beta-cells. Treating 10-week-old ZDF rats with
sustained hyperglycemia with liraglutide resulted in some alleviation of
hyperglycemia, whereas NRTN was not as effective despite improving plasma lipids
and fasting glucose levels. Interestingly, coadministration of NRTN and
liraglutide normalized hyperglycemia and other metabolic parameters,
demonstrating that combining therapies with distinct mechanism(s) can alleviate
advanced diabetes. This emphasizes that therapeutic combinations can be more
effective to manage diabetes in individuals with uncontrolled hyperglycemia.
PMID- 28408436
TI - Cyclin D1 overexpression in proliferation centres of small lymphocytic
lymphoma/chronic lymphocytic leukaemia.
AB - The recent publication reviewing the updated WHO classification commented on the
presence of cyclin D1-positive cells in the proliferation centres (PC) of small
lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL). The figure quoted
was 30%, which appeared higher than our experience. To assess cyclin D1
expression in PC of SLL/CLL cases, we performed a review of SLL/CLL cases
diagnosed at the Royal Marsden Hospital between 1996 and 2009. Of 105 SLL/CLL
cases, 16.2% showed expression of cyclin D1 in PC with none carrying the
translocation t(11;14)(q13;q32). Our study and a review of the published
literature suggest that this phenomenon occurs with a significantly lower
prevalence than that described in the recent review of the updated WHO
classification. We confirm that cyclin D1 expression is confined to PC with the
typical small lymphocytes being negative. This finding is apparently unrelated to
the translocation involving CCND1 and IGH genes.
PMID- 28408437
TI - The MYC mRNA 3'-UTR couples RNA polymerase II function to glutamine and
ribonucleotide levels.
AB - Deregulated expression of MYC enhances glutamine utilization and renders cell
survival dependent on glutamine, inducing "glutamine addiction". Surprisingly,
colon cancer cells that express high levels of MYC due to WNT pathway mutations
are not glutamine-addicted but undergo a reversible cell cycle arrest upon
glutamine deprivation. We show here that glutamine deprivation suppresses
translation of endogenous MYC via the 3'-UTR of the MYC mRNA, enabling escape
from apoptosis. This regulation is mediated by glutamine-dependent changes in
adenosine-nucleotide levels. Glutamine deprivation causes a global reduction in
promoter association of RNA polymerase II (RNAPII) and slows transcriptional
elongation. While activation of MYC restores binding of MYC and RNAPII function
on most promoters, restoration of elongation is imperfect and activation of MYC
in the absence of glutamine causes stalling of RNAPII on multiple genes,
correlating with R-loop formation. Stalling of RNAPII and R-loop formation can
cause DNA damage, arguing that the MYC 3'-UTR is critical for maintaining genome
stability when ribonucleotide levels are low.
PMID- 28408438
TI - PRDM16 represses the type I interferon response in adipocytes to promote
mitochondrial and thermogenic programing.
AB - Brown adipose has the potential to counteract obesity, and thus, identifying
signaling pathways that regulate the activity of this tissue is of great clinical
interest. PRDM16 is a transcription factor that activates brown fat-specific
genes while repressing white fat and muscle-specific genes in adipocytes. Whether
PRDM16 also controls other gene programs to regulate adipocyte function was
unclear. Here, we identify a novel role for PRDM16 in suppressing type I
interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro
and in vivo Ectopic activation of type I IFN signaling in brown adipocytes
induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1)
expression. Prdm16-deficient adipose displays an exaggerated response to type I
IFN, including higher STAT1 levels and reduced mitochondrial gene expression.
Mechanistically, PRDM16 represses ISGs through binding to promoter regions of
these genes and blocking the activating function of IFN regulatory factor 1
(IRF1). Together, these data indicate that PRDM16 diminishes responsiveness to
type I IFN in adipose cells to promote thermogenic and mitochondrial function.
PMID- 28408442
TI - Meet the First Authors.
PMID- 28408439
TI - Sen1 has unique structural features grafted on the architecture of the Upf1-like
helicase family.
AB - The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key
role in the termination of non-coding transcription in yeast. Here, we identified
the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for
transcription termination in vitro and determined the corresponding structure at
1.8 A resolution. In addition to the catalytic and auxiliary subdomains
characteristic of the SF1B family, Sen1 has a distinct and evolutionarily
conserved structural feature that "braces" the helicase core. Comparative
structural analyses indicate that the "brace" is essential in shaping a favorable
conformation for RNA binding and unwinding. We also show that subdomain 1C (the
"prong") is an essential element for 5'-3' unwinding and for Sen1-mediated
transcription termination in vitro Finally, yeast Sen1 mutant proteins mimicking
the disease forms of the human orthologue, senataxin, show lower capacity of RNA
unwinding and impairment of transcription termination in vitro The combined
biochemical and structural data thus provide a molecular model for the
specificity of Sen1 in transcription termination and more generally for the
unwinding mechanism of 5'-3' helicases.
PMID- 28408443
TI - A New Conserved Player in Lymphatic Morphogenesis.
PMID- 28408444
TI - Does Endothelium Buffer Fat?
PMID- 28408445
TI - Synthetic MicroRNAs Stimulate Cardiac Repair.
PMID- 28408446
TI - 3-Dimensionally Printed, Native-Like Scaffolds for Myocardial Tissue Engineering.
PMID- 28408447
TI - Getting A Leg Up on Cell Therapy for Critical Limb Ischemia.
PMID- 28408448
TI - Spermidine Promotes Cardioprotective Autophagy.
PMID- 28408449
TI - The Challenge of Mentorship.
PMID- 28408450
TI - Beyond Mitophagy: The Diversity and Complexity of Parkin Function.
PMID- 28408451
TI - Proliferative Versus Degenerative Paradigms in Pulmonary Arterial Hypertension:
Have We Put the Cart Before the Horse?
PMID- 28408440
TI - Global Cardiovascular and Renal Outcomes of Reduced GFR.
AB - The burden of premature death and health loss from ESRD is well described. Less
is known regarding the burden of cardiovascular disease attributable to reduced
GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on
RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of
cardiovascular outcomes by three categories of reduced GFR were calculated by
pooled random effects meta-analysis. Results are presented as deaths for outcomes
of cardiovascular disease and ESRD and as disability-adjusted life years for
outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In
2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million
deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of
these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to
1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD
related deaths. Compared with metabolic risk factors, reduced GFR ranked below
high systolic BP, high body mass index, and high fasting plasma glucose, and
similarly with high total cholesterol as a risk factor for disability-adjusted
life years in both developed and developing world regions. In conclusion, by
2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths
throughout the world. Studies are needed to evaluate the benefit of early
detection of CKD and treatment to decrease these deaths.
PMID- 28408452
TI - Rigor and Reproducibility in Analysis of Vascular Calcification.
PMID- 28408453
TI - Why Don't We Have Proven Treatments for HFpEF?
PMID- 28408454
TI - Bioresorbable Scaffold: The Emerging Reality and Future Directions.
AB - In the era of drug-eluting stents, large-scale randomized trials and all-comer
registries have shown excellent clinical results. However, even the latest
generation drug-eluting stent has not managed to address all the limitations of
permanent metallic coronary stents, such as the risks of target lesion
revascularization, neoatherosclerosis, preclusion of late lumen enlargement, and
the lack of reactive vasomotion. Furthermore, the risk of very late stent,
although substantially reduced with newer-generation drug-eluting stent, still
remains. These problems were anticipated to be solved with the advent of fully
biodegradable devices. Fully bioresorbable coronary scaffolds have been designed
to function transiently to prevent acute recoil, but have retained the capability
to inhibit neointimal proliferation by eluting immunosuppressive drugs.
Nevertheless, long-term follow-up data of the leading bioresorbable scaffold
(Absorb) are becoming available and have raised a concern about the relatively
higher incidence of scaffold thrombosis. To reduce the rate of clinical events,
improvements in the device, as well as implantation procedure, are being
evaluated. This review will focus on the current CE-mark approved bioresorbable
scaffolds, their basic characteristics, and clinical results. In addition, we
summarize the current limitations of bioresorbable scaffold and their possible
solutions.
PMID- 28408455
TI - Cell Therapy Trials in Congenital Heart Disease.
AB - Dramatic evolution in medical and catheter interventions and complex surgeries to
treat children with congenital heart disease (CHD) has led to a growing number of
patients with a multitude of long-term complications associated with morbidity
and mortality. Heart failure in patients with hypoplastic left heart syndrome
predicated by functional single ventricle lesions is associated with an increase
in CHD prevalence and remains a significant challenge. Pathophysiological
mechanisms contributing to the progression of CHD, including single ventricle
lesions and dilated cardiomyopathy, and adult heart disease may inevitably
differ. Although therapeutic options for advanced cardiac failure are restricted
to heart transplantation or mechanical circulatory support, there is a strong
impetus to develop novel therapeutic strategies. As lower vertebrates, such as
the newt and zebrafish, have a remarkable ability to replace lost cardiac tissue,
this intrinsic self-repair machinery at the early postnatal stage in mice was
confirmed by partial ventricular resection. Although the underlying mechanistic
insights might differ among the species, mammalian heart regeneration occurs even
in humans, with the highest degree occurring in early childhood and gradually
declining with age in adulthood, suggesting the advantage of stem cell therapy to
ameliorate ventricular dysfunction in patients with CHD. Although effective
clinical translation by a variety of stem cells in adult heart disease remains
inconclusive with respect to the improvement of cardiac function, case reports
and clinical trials based on stem cell therapies in patients with CHD may be
invaluable for the next stage of therapeutic development. Dissecting the
differential mechanisms underlying progressive ventricular dysfunction in
children and adults may lead us to identify a novel regenerative therapy. Future
regenerative technologies to treat patients with CHD are exciting prospects for
heart regeneration in general practice.
PMID- 28408456
TI - Correction to: Identification of a Retinal Aldosterone System and the Protective
Effects of Mineralocorticoid Receptor Antagonism on Retinal Vascular Pathology.
PMID- 28408457
TI - Correction to: beta-Adrenergic Signaling Inhibits Gq-Dependent Protein Kinase D
Activation by Preventing Protein Kinase D Translocation and Multimodal SHG-2PF
Imaging of Microdomain Ca2+-Contraction Coupling in Live Cardiac Myocytes.
PMID- 28408458
TI - London commissioning group plans to restrict cataract surgery to "exceptional"
cases.
PMID- 28408459
TI - EPCR expression marks UM171-expanded CD34+ cord blood stem cells.
AB - A small subset of human cord blood CD34+ cells express endothelial protein C
receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC)
self-renewal agonist UM171. In this article, we show that EPCR-positive UM171
treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage
repopulation and serial reconstitution ability in immunocompromised mice. In
contrast to other stem cell markers, such as CD38, EPCR expression is maintained
when cells are introduced in culture, irrespective of UM171 treatment. Although
engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC
activity, its expression is required for the repopulating activity of human HSCs.
Altogether, our results indicate that EPCR is a reliable and cell culture
compatible marker of UM171-expanded human cord blood HSCs.
PMID- 28408460
TI - Can histologic transformation of follicular lymphoma be predicted and prevented?
AB - Transformation to aggressive lymphoma is a critical event in the clinical course
of follicular lymphoma (FL) patients. Yet, it is a challenge to reliably predict
transformation at the time of diagnosis. Understanding the risk of transformation
would be useful for guiding and monitoring patients, as well as for evaluating
novel treatment strategies that could potentially prevent transformation. Herein,
we review the contribution of clinical, pathological, and genetic risk factors to
transformation. Patients with multiple clinical high-risk factors are at elevated
risk of transformation but we are currently lacking a prognostic index that would
specifically address transformation rather than disease progression or overall
survival. From the biological standpoint, multiple studies have correlated
individual biomarkers with transformation. However, accurate prediction of this
event is currently hampered by our limited knowledge of the evolutionary pathways
leading to transformation, as well as the scarcity of comprehensive, large-scale
studies that assess both the genomic landscape of alterations within tumor cells
and the composition of the microenvironment. Liquid biopsies hold great promise
for achieving precision medicine. Indeed, mutations detected within circulating
tumor DNA may be a better reflection of the inherent intratumoral heterogeneity
than the biopsy of a single site. Last, we will assess whether evidence exists in
the literature that transformation might be prevented altogether, based on the
choice of therapy for FL.
PMID- 28408461
TI - Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia
identifies oncogene enhancer mutations.
PMID- 28408462
TI - Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and
dose in children and young adults.
AB - Transitioning CD19-directed chimeric antigen receptor (CAR) T cells from early
phase trials in relapsed patients to a viable therapeutic approach with
predictable efficacy and low toxicity for broad application among patients with
high unmet need is currently complicated by product heterogeneity resulting from
transduction of undefined T-cell mixtures, variability of transgene expression,
and terminal differentiation of cells at the end of culture. A phase 1 trial of
45 children and young adults with relapsed or refractory B-lineage acute
lymphoblastic leukemia was conducted using a CD19 CAR product of defined CD4/CD8
composition, uniform CAR expression, and limited effector differentiation.
Products meeting all defined specifications occurred in 93% of enrolled patients.
The maximum tolerated dose was 106 CAR T cells per kg, and there were no deaths
or instances of cerebral edema attributable to product toxicity. The overall
intent-to-treat minimal residual disease-negative (MRD-) remission rate for this
phase 1 study was 89%. The MRD- remission rate was 93% in patients who received a
CAR T-cell product and 100% in the subset of patients who received fludarabine
and cyclophosphamide lymphodepletion. Twenty-three percent of patients developed
reversible severe cytokine release syndrome and/or reversible severe
neurotoxicity. These data demonstrate that manufacturing a defined-composition
CD19 CAR T cell identifies an optimal cell dose with highly potent antitumor
activity and a tolerable adverse effect profile in a cohort of patients with an
otherwise poor prognosis. This trial was registered at www.clinicaltrials.gov as
#NCT02028455.
PMID- 28408463
TI - Bone marrow histology for the diagnosis of essential thrombocythemia in children:
a multicenter Italian study.
PMID- 28408465
TI - Human definitive hematopoietic specification from pluripotent stem cells is
regulated by mesodermal expression of CDX4.
AB - The generation of hematopoietic stem cells from human pluripotent stem cells
(hPSCs) is a major goal for regenerative medicine. Achieving this goal is
complicated by our incomplete understanding of the mechanism regulating
definitive hematopoietic specification. We used our stage-specific hPSC
differentiation method to obtain and identify, via CD235a expression, mesoderm
harboring exclusively primitive or definitive hematopoietic potential to
understand the genetic regulation of definitive hematopoietic specification.
Whole-transcriptome gene expression analyses on WNT-dependent KDR+CD235a-
definitive hematopoietic mesoderm and WNT-independent KDR+CD235a+ primitive
hematopoietic mesoderm revealed strong CDX gene expression within definitive
hematopoietic mesoderm. Temporal expression analyses revealed that CDX4 was
expressed exclusively within definitive hematopoietic KDR+CD235a- mesoderm in a
WNT- and fibroblast growth factor-dependent manner. We found that exogenous CDX4
expression exclusively during mesoderm specification resulted in a >90%
repression in primitive hematopoietic potential, but conferred fivefold greater
definitive hematopoietic potential, similar to that observed following WNT
stimulation. In contrast, CDX4 knockout hPSCs had intact primitive hematopoietic
potential, but exhibited a fivefold decrease in multilineage definitive
hematopoietic potential. Taken together, these findings indicate that CDX4 is a
critical transcription factor in the regulation of human definitive hematopoietic
specification, and provides a mechanistic basis for WNT-mediated definitive
hematopoietic specification from hPSCs.
PMID- 28408466
TI - 'Best interests' in paediatric intensive care: an empirical ethics study.
AB - OBJECTIVE: In English paediatric practice, English law requires that parents and
clinicians agree the 'best interests' of children and, if this is not possible,
that the courts decide. Court intervention is rare and the concept of best
interests is ambiguous. We report qualitative research exploring how the best
interests standard operates in practice, particularly with decisions related to
planned non-treatment. We discuss results in the light of accounts of best
interests in the medical ethics literature. DESIGN: We conducted 39 qualitative
interviews, exploring decision making in the paediatric intensive care unit, with
doctors, nurses, clinical ethics committee members and parents whose children had
a range of health outcomes. Interviews were audio-recorded and analysed
thematically. RESULTS: Parents and clinicians indicated differences in their
approaches to deciding the child's best interests. These were reconciled when
parents responded positively to clinicians' efforts to help parents agree with
the clinicians' view of the child's best interests. Notably, protracted
disagreements about a child's best interests in non-treatment decisions were
resolved when parents' views were affected by witnessing their child's physical
deterioration. Negotiation was the norm and clinicians believed avoiding the
courts was desirable. CONCLUSIONS: Sensitivity to the long-term interests of
parents of children with life-limiting conditions is defensible but must be
exercised proportionately. Current approaches emphasise negotiation but offer few
alternatives when decisions are at an impasse. In such situations, the
instrumental role played by a child's deterioration and avoidance of the courts
risks giving insufficient weight to the child's interests. New approaches to
decision making are needed.
PMID- 28408464
TI - Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's
Oncology Group.
AB - Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a
high-risk subtype characterized by genomic alterations that activate cytokine
receptor and kinase signaling. We examined the frequency and spectrum of
targetable genetic lesions in a retrospective cohort of 1389 consecutively
diagnosed patients with childhood B-lineage ALL with high-risk clinical features
and/or elevated minimal residual disease at the end of remission induction
therapy. The Ph-like gene expression profile was identified in 341 of 1389
patients, 57 of whom were excluded from additional analyses because of the
presence of BCR-ABL1 (n = 46) or ETV6-RUNX1 (n = 11). Among the remaining 284
patients (20.4%), overexpression and rearrangement of CRLF2 (IGH-CRLF2 or P2RY8
CRLF2) were identified in 124 (43.7%), with concomitant genomic alterations
activating the JAK-STAT pathway (JAK1, JAK2, IL7R) identified in 63 patients
(50.8% of those with CRLF2 rearrangement). Among the remaining patients, using
reverse transcriptase polymerase chain reaction or transcriptome sequencing, we
identified targetable ABL-class fusions (ABL1, ABL2, CSF1R, and PDGFRB) in 14.1%,
EPOR rearrangements or JAK2 fusions in 8.8%, alterations activating other JAK
STAT signaling genes (IL7R, SH2B3, JAK1) in 6.3% or other kinases (FLT3, NTRK3,
LYN) in 4.6%, and mutations involving the Ras pathway (KRAS, NRAS, NF1, PTPN11)
in 6% of those with Ph-like ALL. We identified 8 new rearrangement partners for 4
kinase genes previously reported to be rearranged in Ph-like ALL. The current
findings provide support for the precision-medicine testing and treatment
approach for Ph-like ALL implemented in Children's Oncology Group ALL trials.
PMID- 28408467
TI - Isolated mild sleep-associated hypoventilation in children with Down syndrome.
AB - INTRODUCTION: Children with Down syndrome (DS) have a high incidence of
obstructive sleep apnea (OSA) that is often associated with hypoventilation.
Little is known, however, about the prevalence of sleep-associated
hypoventilation independent of OSA in these children. METHODS: Retrospective
chart review of all children with DS under 18 years of age undergoing
polysomnography at a tertiary care paediatric hospital during a 2-year period.
Exclusion criteria were as follow: those requiring oxygen or positive-pressure
ventilation; with tracheostomy, baseline hypoxia, unrepaired cyanotic heart
disease, pulmonary hypertension, and cerebral palsy; or OSA with >5
obstructions/hour. RESULTS: 86 children met inclusion criteria. 68 (79%) had
ETCO2values >50 mm Hg during sleep. 37 (43%) ranged 50-55 mm Hg, and 12 (14%) met
American Academy of Sleep Medicine criteria for hypoventilation of ETCO2 >50 mm
Hg for >25% of total sleep time (TST). Average pulse-oximetry saturation (SpO2)
values during sleep were 97.8% (SD +/-1; range: 95.1-99.9). Average percentage of
TST with SpO2 >92% was 99.89%. CONCLUSION: Mildly elevated ETCO2 in the absence
of OSA is common in children with DS. This may reflect underlying differences in
autonomic control of ventilation in these children and may be considered a normal
variant not necessitating intervention other than close monitoring for pulmonary
hypertension.
PMID- 28408468
TI - Avoidance of voiding cystourethrography in infants younger than 3 months with
Escherichia coli urinary tract infection and normal renal ultrasound.
AB - BACKGROUND AND OBJECTIVE: Urinary tract infection (UTI) represents the most
common bacterial infection in infants, and its prevalence increases with the
presence of high-grade vesicoureteral reflux (VUR). However, voiding
cystourethrography (VCUG) is invasive, and its indication in infants <3 months is
not yet defined. This study aims to investigate, in infants aged 0-3 months, if
the presence of Escherichia coli versus non-E. coli bacteria and/or normal or
abnormal renal ultrasound (US) could avoid the use of VCUG. METHOD: One hundred
and twenty-two infants with a first febrile UTI were enrolled. High-grade VUR was
defined by the presence of VUR grade >=III. The presence of high-grade VUR was
recorded using VCUG, and correlated with the presence of E. coli/non-E. coli UTI
and with the presence of normal/abnormal renal US. The Bayes theorem was used to
calculate pretest and post-test probability. RESULTS: The probability of high
grade VUR was 3% in the presence of urinary E. coli infection. Adding a normal
renal US finding decreased this probability to 1%. However, in the presence of
non-E. coli bacteria, the probability of high-grade VUR was 26%, and adding an
abnormal US finding increased further this probability to 55%. CONCLUSIONS: In
infants aged 0-3 months with a first febrile UTI, the presence of E. coli and
normal renal US findings allow to safely avoid VCUG. Performing VCUG only in
infants with UTI secondary to non-E. coli bacteria and/or abnormal US would save
many unnecessary invasive procedures, limit radiation exposure, with a very low
risk (<1%) of missing a high-grade VUR.
PMID- 28408469
TI - Cell wall-deficient, L-form bacteria in the 21st century: a personal perspective.
AB - The peptidoglycan (PG) cell wall is a defining feature of the bacteria. It
emerged very early in evolution and must have contributed significantly to the
success of these organisms. The wall features prominently in our thinking about
bacterial cell function, and its synthesis involves the action of several dozen
proteins that are normally essential for viability. Surprisingly, it turns out to
be relatively simple to generate bacterial genetic variants called L-forms that
completely lack PG. They grow robustly provided that lack of the cell wall is
compensated for by an osmoprotective growth medium. Although their existence has
been noted and studied on and off for many decades, it is only recently that
modern molecular and cellular methods have been applied to L-forms. We used
Bacillus subtilis as an experimental model to understand the molecular basis for
the L-form switch. Key findings included the discovery that L-forms use an
unusual blebbing, or tubulation and scission mechanism to proliferate. This
mechanism is completely independent of the normal FtsZ-based division machinery
and seems to require only an increased rate of membrane synthesis, leading to an
increased surface area-to-volume ratio. Antibiotics that block cell wall
precursor synthesis, such as phosphomycin, efficiently induce the L-form switch
without the need for genetic change. The same antibiotics turned out to induce a
similar L-form switch in a wide range of bacteria, including Escherichia coli, in
which we showed that proliferation was again FtsZ-independent. Aside from further
basic science, future work on L-forms is likely to focus on their possible role
in chronic or recurrent infections, their use as a model in studies of the
origins of life, and possibly, biotechnological applications.
PMID- 28408470
TI - Inspired by lipids: the Morton Lecture Award Presentation.
AB - Lipids are key molecules for membranes, energy storage and signalling. I have
been privileged to have worked in such a diverse field and in organisms from
microbes to humans. Here I will describe some of those contrasting areas which
range from environmental impacts to food production and on to human health. It
has been a fascinating journey which still continues to excite me.
PMID- 28408471
TI - Genomes, structural biology and drug discovery: combating the impacts of
mutations in genetic disease and antibiotic resistance.
AB - For over four decades structural biology has been used to understand the
mechanisms of disease, and structure-guided approaches have demonstrated clearly
that they can contribute to many aspects of early drug discovery, both
computationally and experimentally. Structure can also inform our understanding
of impacts of mutations in human genetic diseases and drug resistance in cancers
and infectious diseases. We discuss the ways that structural insights might be
useful in both repurposing off-licence drugs and guide the design of new
molecules that might be less susceptible to drug resistance in the future.
PMID- 28408473
TI - O-GlcNAcylation and chromatin remodeling in mammals: an up-to-date overview.
AB - Post-translational modifications of histones and the dynamic DNA methylation
cycle are finely regulated by a myriad of chromatin-binding factors and chromatin
modifying enzymes. Epigenetic modifications ensure local changes in the
architecture of chromatin, thus controlling in fine the accessibility of the
machinery of transcription, replication or DNA repair to the chromatin. Over the
past decade, the nutrient-sensor enzyme O-GlcNAc transferase (OGT) has emerged as
a modulator of chromatin remodeling. In mammals, OGT acts either directly through
dynamic and reversible O-GlcNAcylation of histones and chromatin effectors, or in
an indirect manner through its recruitment into chromatin-bound multiprotein
complexes. In particular, there is an increasing amount of evidence of a cross
talk between OGT and the DNA dioxygenase ten-eleven translocation proteins that
catalyze active DNA demethylation. Conversely, the stability of OGT itself can be
controlled by the histone lysine-specific demethylase 2 (LSD2). Finally, a few
studies have explored the role of O-GlcNAcase (OGA) in chromatin remodeling. In
this review, we summarize the recent findings on the link between OGT, OGA and
chromatin regulators in mammalian cellular models, and discuss their relevance in
physiological and pathological conditions.
PMID- 28408472
TI - The sweet side of the cell cycle.
AB - Cell division (mitosis) and gamete production (meiosis) are fundamental
requirements for normal organismal development. The mammalian cell cycle is
tightly regulated by different checkpoints ensuring complete and precise
chromosomal segregation and duplication. In recent years, researchers have become
increasingly interested in understanding how O-GlcNAc regulates the cell cycle.
The O-GlcNAc post-translation modification is an O-glycosidic bond of a single
beta-N-acetylglucosamine sugar to serine/threonine residues of intracellular
proteins. This modification is sensitive toward changes in nutrient levels in the
cellular environment making O-GlcNAc a nutrient sensor capable of influencing
cell growth and proliferation. Numerous studies have established that O
GlcNAcylation is essential in regulating mitosis and meiosis, while loss of O
GlcNAcylation is lethal in growing cells. Moreover, aberrant O-GlcNAcylation is
linked with cancer and chromosomal segregation errors. In this review, we will
discuss how O-GlcNAc controls different aspects of the cell cycle with a
particular emphasis on mitosis and meiosis.
PMID- 28408474
TI - When mRNA translation meets decay.
AB - Messenger RNA (mRNA) translation and mRNA degradation are important determinants
of protein output, and they are interconnected. Previously, it was thought that
translation of an mRNA, as a rule, prevents its degradation. mRNA surveillance
mechanisms, which degrade mRNAs as a consequence of their translation, were
considered to be exceptions to this rule. Recently, however, it has become clear
that many mRNAs are degraded co-translationally, and it has emerged that codon
choice, by influencing the rate of ribosome elongation, affects the rate of mRNA
decay. In this review, we discuss the links between translation and mRNA
stability, with an emphasis on emerging data suggesting that codon optimality may
regulate mRNA degradation.
PMID- 28408475
TI - Regulation of human immunodeficiency virus type 1 (HIV-1) mRNA translation.
AB - Human immunodeficiency virus type 1 (HIV-1) mRNA translation is a complex process
that uses the host translation machinery to synthesise viral proteins. Several
mechanisms for HIV-1 mRNA translation initiation have been proposed including (1)
cap-dependent, eIF4E-dependent, (2) cap-dependent, cap-binding complex-dependent,
(3) internal ribosome entry sites, and (4) ribosome shunting. While these
mechanisms promote HIV-1 mRNA translation in the context of in vitro systems and
subgenomic constructs, there are substantial knowledge gaps in understanding how
they regulate viral protein production in the context of full-length virus
infection. In this review, we will summarise the different translation mechanisms
used by HIV-1 mRNAs and the challenges in understanding how they regulate protein
synthesis during viral infection.
PMID- 28408476
TI - OGT: a short overview of an enzyme standing out from usual glycosyltransferases.
AB - O-GlcNAcylation is a highly dynamic post-translational modification whose level
depends on nutrient status. Only two enzymes regulate O-GlcNAcylation cycling,
the glycosyltransferase OGT (O-GlcNAc transferase) and the glycoside hydrolase
OGA (O-GlcNAcase), that add and remove the GlcNAc moiety to and from acceptor
proteins, respectively. During the last 30 years, OGT has emerged as a master
regulator of cell life with O-GlcNAcylation being found in viruses, bacteria,
insects, protists and metazoans. The study of OGT in different biological systems
opens new perspectives for understanding this enzyme in many kingdoms of life. In
this review, we summarize recent and older findings regarding the distribution of
OGT in living organisms.
PMID- 28408478
TI - Antagonistic roles for STYX pseudophosphatases in neurite outgrowth.
AB - Mitogen-activated protein kinases (MAPKs) are essential players in important
neuronal signaling pathways including neuronal development, plasticity, survival,
learning, and memory. The inactivation of MAPKs is tightly controlled by MAPK
phosphatases (MKPs), which also are important regulators of these neuronal
processes. Considering that MAPKs and MKPs are major players in neuronal
signaling, it follows that their misregulation is pivotal in neurodegenerative
diseases such as Alzheimer's, Huntington's, Parkinson's, and amyotrophic lateral
sclerosis. In contrast, the actions of their noncatalytic homologs, or
pseudoenzymes, have received minimal attention as important regulators in
neuronal signaling pathways and relevant diseases. There is compelling evidence,
however, that pseudophosphatases, such as STYX (phospho-serine-threonine/tyrosine
binding protein) and MAPK-STYX (MK-STYX), are integral signaling molecules in
regulating pathways involved in neuronal developmental processes such as neurite
outgrowth. Here, we discuss how the dynamics of MK-STYX in the stress response
pathway imply that this unique member of the MKP subfamily has the potential to
have a major role in neuronal signaling. We further compare the actions of STYX
in preventing neurite-like outgrowths and MK-STYX in inducing neurite outgrowths.
The roles of these pseudophosphatases in neurite outgrowth highlight their
emergence as important candidates to investigate in neurodegenerative disorders
and diseases.
PMID- 28408477
TI - Pseudoscaffolds and anchoring proteins: the difference is in the details.
AB - Pseudokinases and pseudophosphatases possess the ability to bind substrates
without catalyzing their modification, thereby providing a mechanism to recruit
potential phosphotargets away from active enzymes. Since many of these
pseudoenzymes possess other characteristics such as localization signals,
separate catalytic sites, and protein-protein interaction domains, they have the
capacity to influence signaling dynamics in local environments. In a similar
manner, the targeting of signaling enzymes to subcellular locations by A-kinase
anchoring proteins (AKAPs) allows for precise and local control of second
messenger signaling events. Here, we will discuss how pseudoenzymes form
'pseudoscaffolds' and compare and contrast this compartment-specific regulatory
role with the signal organization properties of AKAPs. The mitochondria will be
the focus of this review, as they are dynamic organelles that influence a broad
range of cellular processes such as metabolism, ATP synthesis, and apoptosis.
PMID- 28408479
TI - How do they stick together? Bacterial adhesins implicated in the binding of
bacteria to the human gastrointestinal mucins.
AB - The gastrointestinal mucosal surface is the primary interface between internal
host tissues and the vast microbiota. Mucins, key components of mucus, are high
molecular-weight glycoproteins characterized by the presence of many O-linked
oligosaccharides to the core polypeptide. They play many biological functions,
helping to maintain cellular homeostasis and to establish symbiotic relationships
with complex microbiota. Mucin O-glycans exhibit a huge variety of peripheral
sequences implicated in the binding of bacteria to the mucosal tissues, thereby
playing a key role in the selection of specific species and in the tissue tropism
displayed by commensal and pathogenic bacteria. Bacteria have evolved numerous
strategies to colonize host mucosae, and among these are modulation of expression
of cell surface adhesins which allow bacteria to bind to mucins. However, despite
well structurally characterized adhesins and lectins, information on the nature
and structure of oligosaccharides recognized by bacteria is still disparate. This
review summarizes the current knowledge on the structure of epithelial mucin O
glycans and the interaction between host and commensal or pathogenic bacteria
mediated by mucins.
PMID- 28408480
TI - EOGT and O-GlcNAc on secreted and membrane proteins.
AB - Here, we describe a recently discovered O-GlcNAc transferase termed EOGT for EGF
domain-specific O-GlcNAc transferase. EOGT transfers GlcNAc (N-acetylglucosamine)
to Ser or Thr in secreted and membrane proteins that contain one or more
epidermal growth factor-like repeats with a specific consensus sequence. Thus,
EOGT is distinct from OGT, the O-GlcNAc transferase, that transfers GlcNAc to
Ser/Thr in proteins of the cytoplasm or nucleus. EOGT and OGT are in separate
cellular compartments and have mostly distinct substrates, although both can act
on cytoplasmic (OGT) and lumenal (EOGT) domains of transmembrane proteins. The
present review will describe known substrates of EOGT and biological roles for
EOGT in Drosophila and humans. Mutations in EOGT that give rise to Adams-Oliver
Syndrome in humans will also be discussed.
PMID- 28408481
TI - Palmitoylation of proteins in cancer.
AB - Post-translational modification of proteins by attachment of palmitate serves as
a mechanism to regulate protein localization and function in both normal and
malignant cells. Given the essential role that palmitoylation plays in cancer
cell signaling, approaches that target palmitoylated proteins and palmitoyl
acyltransferases (PATs) have the potential for therapeutic intervention in
cancer. Highlighted here are recent advances in understanding the importance of
protein palmitoylation in tumorigenic pathways. A new study has uncovered
palmitoylation sites within the epidermal growth factor receptor that regulate
receptor trafficking, signaling and sensitivity to tyrosine kinase inhibitors.
Global data analysis from nearly 150 cancer studies reveals genomic alterations
in several PATs that may account for their ability to function as tumor
suppressors or oncogenes. Selective inhibitors have recently been developed that
target hedgehog acyltransferase (Hhat) and Porcupine (Porcn), the
acyltransferases that modify hedgehog and Wnt proteins, respectively. These
inhibitors, coupled with targeted knockdown of Hhat and Porcn, reveal the
essential functions of fatty acylation of secreted morphogens in a wide variety
of human tumors.
PMID- 28408482
TI - Small regulatory bacterial RNAs regulating the envelope stress response.
AB - Most bacteria encode a large repertoire of RNA-based regulatory mechanisms.
Recent discoveries have revealed that the expression of many genes is controlled
by a plethora of base-pairing noncoding small regulatory RNAs (sRNAs), regulatory
RNA-binding proteins and RNA-degrading enzymes. Some of these RNA-based regulated
processes respond to stress conditions and are involved in the maintenance of
cellular homeostasis. They achieve it by either direct posttranscriptional
repression of several mRNAs, including blocking access to ribosome and/or
directing them to RNA degradation when the synthesis of their cognate proteins is
unwanted, or by enhanced translation of some key stress-regulated transcriptional
factors. Noncoding RNAs that regulate the gene expression by binding to
regulatory proteins/transcriptional factors often act negatively by
sequestration, preventing target recognition. Expression of many sRNAs is
positively regulated by stress-responsive sigma factors like RpoE and RpoS, and
two-component systems like PhoP/Q, Cpx and Rcs. Some of these regulatory RNAs act
via a feedback mechanism on their own regulators, which is best reflected by
recent discoveries, concerning the regulation of cell membrane composition by
sRNAs in Escherichia coli and Salmonella, which are highlighted here.
PMID- 28408484
TI - Joint features and complementarities of Tspan8 and CD151 revealed in knockdown
and knockout models.
AB - Tetraspanins are highly conserved 4-transmembrane proteins which form molecular
clusters with a large variety of transmembrane and cytosolic proteins. By these
associations tetraspanins are engaged in a multitude of biological processes.
Furthermore, tetraspanin complexes are located in specialized microdomains,
called tetraspanin-enriched microdomains (TEMs). TEMs provide a signaling
platform and are poised for invagination and vesicle formation. These vesicles
can be released as exosomes (Exo) and are important in cell contact-independent
intercellular communication. Here, we summarize emphasizing knockdown and
knockout models' pathophysiological joint and selective activities of CD151 and
Tspan8, and discuss the TEM-related engagement of CD151 and Tspan8 in Exo
activities.
PMID- 28408483
TI - O-GlcNAc cycling and the regulation of nucleocytoplasmic dynamics.
AB - The dynamic carbohydrate post-translational modification (PTM) O-linked beta-N
acetyl glucosamine (O-GlcNAc) is found on thousands of proteins throughout the
nucleus and cytoplasm, and rivals phosphorylation in terms of the number of
substrates and pathways influenced. O-GlcNAc is highly conserved and essential in
most organisms, with disruption of O-GlcNAc cycling linked to diseases ranging
from cancer to neurodegeneration. Nuclear pore proteins were the first identified
O-GlcNAc-modified substrates, generating intense and ongoing interest in
understanding the role of O-GlcNAc cycling in nuclear pore complex structure and
function. Recent advances in detecting and altering O-GlcNAcylation levels have
provided insights into many mechanisms by which O-GlcNAcylation influences the
nucleocytoplasmic localization and stability of protein targets. The emerging
view is that the multifunctional enzymes of O-GlcNAc cycling are critical
nutrient-sensing components of a complex network of signaling cascades involving
multiple PTMs. Furthermore, O-GlcNAc plays a role in maintaining the structural
integrity of the nuclear pore and regulating its function as the gatekeeper of
nucleocytoplasmic trafficking.
PMID- 28408485
TI - STYX: a versatile pseudophosphatase.
AB - The pseudophosphatase STYX (serine/threonine/tyrosine interacting protein) is a
catalytically inactive member of the protein tyrosine phosphatase family. We
perform a phylogenetic analysis of STYX and ask how far does the pseudoenzyme
status of STYX reaches in evolution. Based on our previous work, we use STYX as a
showcase to discuss four basic modes of action that any given pseudoenzyme may
exert. Our previous work on the effect of STYX on mitogen-activated protein
kinase (MAPK) signaling led us to identify two complementary modes of action. On
the one hand, STYX competes with active phosphatases for binding to MAPKs. On the
other hand, STYX acts as a nuclear anchor for MAPKs, affecting their nucleo
cytoplasmic shuttling. Finally, we discuss our recent work on the regulation of
FBXW7 by this pseudophosphatase and how it affects the ubiquitylation and
degradation of its substrates. We discuss the biological significance of this
regulatory mechanism and use it as an example for the versatility of
pseudoenzymes that may divert away from merely regulating their active homologs.
PMID- 28408486
TI - Targeting ROR1 identifies new treatment strategies in hematological cancers.
AB - Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR
receptor family consisting of two closely related type I transmembrane proteins
ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper
kinase activity, RORs are classified as pseudokinases lacking detectable
catalytic activity. ROR1 stands out for its selective and high expression in
numerous blood and solid malignancies compared with a minimal expression in
healthy adult tissues, suggesting high potential for this molecule as a drug
target for cancer therapy. Current understanding attributes a survival role for
ROR1 in cancer cells; however, its oncogenic function is cancer-type-specific and
involves various signaling pathways. High interest in ROR1-targeted therapies
resulted in the development of ROR1 monoclonal antibodies such as cirmtuzumab,
currently in a phase I clinical trial for chronic lymphocytic leukemia. Despite
these advances in translational studies, the molecular mechanism employed by ROR1
in different cancers is not yet fully understood; therefore, more insights into
the oncogenic role of ROR1 signaling are crucial in order to optimize the use of
targeted drugs. Recent studies provided evidence that targeting ROR1
simultaneously with inhibition of B-cell receptor (BCR) signaling is more
effective in killing ROR1-positive leukemia cells, suggesting a synergistic
correlation between co-targeting ROR1 and BCR pathways. Although this synergy has
been previously reported for B-cell acute lymphoblastic leukemia, the molecular
mechanism appears rather different. These results provide more insights into ROR1
BCR combinatorial treatment strategies in hematological malignancies, which could
benefit in tailoring more effective targeted therapies in other ROR1-positive
cancers.
PMID- 28408488
TI - Mitochondria-organelle contact sites: the plot thickens.
AB - Membrane contact sites (MCSs) are areas of close apposition between the membranes
of two different organelles that enable non-vesicular transfer of ions and
lipids. Recent studies reveal that mitochondria maintain contact sites with
organelles other than the endoplasmic reticulum such as the vacuole, plasma
membrane and peroxisomes. This review focuses on novel findings achieved mainly
in yeast regarding tethers, function and regulation of mitochondria-organelle
contact sites. The emerging network of MCSs linking virtually all cellular
organelles is highly dynamic and integrated with cellular metabolism.
PMID- 28408489
TI - Tetraspanins in infections by human cytomegalo- and papillomaviruses.
AB - Members of the tetraspanin family have been identified as essential cellular
membrane proteins in infectious diseases by nearly all types of pathogens. The
present review highlights recently published data on the role of tetraspanin
CD151, CD81, and CD63 and their interaction partners in host cell entry by human
cytomegalo- and human papillomaviruses. Moreover, we discuss a model for
tetraspanin assembly into trafficking platforms at the plasma membrane. These
platforms might persist during intracellular viral trafficking.
PMID- 28408487
TI - Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer
metastasis.
AB - Tetraspanin 2 (Tspan2) is one of the less well-characterised members of the
tetraspanin superfamily, and its precise function in different human tissue types
remains to be explored. Initial studies have highlighted its possible association
in neuroinflammation and carcinogenesis. In the central nervous system, Tspan2
may contribute to the early stages of the oligodendrocyte differentiation into
myelin-forming glia. Furthermore, in human lung cancer, Tspan2 could be involved
in the progression of the tumour metastasis by modulating cancer cell motility
and invasion functions. In this review, we discuss the available evidence for the
potential role of Tspan2 and introduce possible strategies for disease targeting.
PMID- 28408490
TI - Atomic force microscopy of virus shells.
AB - Microscopes are used to characterize small objects with the help of probes that
interact with the specimen, such as photons and electrons in optical and electron
microscopies, respectively. In atomic force microscopy (AFM), the probe is a
nanometric tip located at the end of a microcantilever which palpates the
specimen under study just as a blind person manages a walking stick. In this way,
AFM allows obtaining nanometric resolution images of individual protein shells,
such as viruses, in a liquid milieu. Beyond imaging, AFM also enables not only
the manipulation of single protein cages, but also the characterization of every
physicochemical property capable of inducing any measurable mechanical
perturbation to the microcantilever that holds the tip. In the present revision,
we start revising some recipes for adsorbing protein shells on surfaces. Then, we
describe several AFM approaches to study individual protein cages, ranging from
imaging to spectroscopic methodologies devoted to extracting physical
information, such as mechanical and electrostatic properties. We also explain how
a convenient combination of AFM and fluorescence methodologies entails monitoring
genome release from individual viral shells during mechanical unpacking.
PMID- 28408492
TI - CD81 as a tumor target.
AB - CD81 participates in a variety of important cellular processes such as membrane
organization, protein trafficking, cellular fusion and cell-cell interactions. In
the immune system, CD81 regulates immune synapse, receptor clustering and
signaling; it also mediates adaptive and innate immune suppression. CD81 is a
gateway in hepatocytes for pathogens such as hepatitis C virus and Plasmodium; it
also confers susceptibility to Listeria infection. These diverse biological roles
are due to the tendency of CD81 to associate with other tetraspanins and with
cell-specific partner proteins, which provide the cells with a signaling
platform. CD81 has also been shown to regulate cell migration and invasion, and
has therefore been implicated in cancer progression. Indeed, we have recently
shown that CD81 contributes to tumor growth and metastasis. CD81 is expressed in
most types of cancer, including breast, lung, prostate, melanoma, brain cancer
and lymphoma, and the overexpression or down-regulation of this molecule has been
correlated with either good or bad prognosis. Here, we discuss the role of CD81
in cancer and its potential therapeutic use as a tumor target.
PMID- 28408493
TI - Bio-Zombie: the rise of pseudoenzymes in biology.
AB - Pseudoenzymes are catalytically dead counterparts of enzymes. Despite their first
description some 50 years ago, the importance and functional diversity of these
'fit-for-purpose' polypeptides is only now being appreciated. Pseudoenzymes have
been identified throughout all the kingdoms of life and, owing to predicted
deficits in enzyme activity due to the absence of catalytic residues, have been
variously referred to as pseudoenzymes, non-enzymes, dead enzymes, prozymes or
'zombie' proteins. An important goal of the recent Biochemical Society
Pseudoenzymes-focused meeting was to explore the functional and evolutionary
diversity of pseudoenzymes and to begin to evaluate their functions in biology,
including cell signalling and metabolism. Here, we summarise the impressive
breadth of enzyme classes that are known to have pseudoenzyme counterparts and
present examples of known cellular functions. We predict that the next decades
will represent golden years for the analysis of pseudoenzymes.
PMID- 28408491
TI - Mitochondrial DNA replication: a PrimPol perspective.
AB - PrimPol, (primase-polymerase), the most recently identified eukaryotic
polymerase, has roles in both nuclear and mitochondrial DNA maintenance. PrimPol
is capable of acting as a DNA polymerase, with the ability to extend primers and
also bypass a variety of oxidative and photolesions. In addition, PrimPol also
functions as a primase, catalysing the preferential formation of DNA primers in a
zinc finger-dependent manner. Although PrimPol's catalytic activities have been
uncovered in vitro, we still know little about how and why it is targeted to the
mitochondrion and what its key roles are in the maintenance of this multicopy DNA
molecule. Unlike nuclear DNA, the mammalian mitochondrial genome is circular and
the organelle has many unique proteins essential for its maintenance, presenting
a differing environment within which PrimPol must function. Here, we discuss what
is currently known about the mechanisms of DNA replication in the mitochondrion,
the proteins that carry out these processes and how PrimPol is likely to be
involved in assisting this vital cellular process.
PMID- 28408495
TI - Expanding the genetic code of mammalian cells.
AB - In the last two decades, unnatural amino acid (UAA) mutagenesis has emerged as a
powerful new method to probe and engineer protein structure and function. This
technology enables precise incorporation of a rapidly expanding repertoire of
UAAs into predefined sites of a target protein expressed in living cells. Owing
to the small footprint of these genetically encoded UAAs and the large variety of
enabling functionalities they offer, this technology has tremendous potential for
deciphering the delicate and complex biology of the mammalian cells. Over the
last few years, exciting progress has been made toward expanding the toolbox of
genetically encoded UAAs in mammalian cells, improving the efficiency of their
incorporation and developing innovative applications. Here, we provide our
perspective on these recent developments and highlight the current challenges
that must be overcome to realize the full potential of this technology.
PMID- 28408494
TI - O-GlcNAcylation and cardiovascular disease.
AB - The post-translational modification of serine and threonine residues of proteins
found in numerous subcellular locations by O-linked N-acetylglucosamine (O
GlcNAc) is emerging as a key mediator of many cardiovascular pathophysiological
processes. Early studies implicated increased protein O-GlcNAcylation as
contributing to the cardiovascular complications associated with diabetes,
whereas subsequent studies demonstrated that acute increases in O-GlcNAc levels
were protective against ischemia/reperfusion injury. There is now a growing
understanding that O-GlcNAc modification of proteins influences numerous cellular
functions, including transcription, protein turnover, calcium handling, and
bioenergetics. As a result, a more nuanced view of the role of protein O
GlcNAcylation in the cardiovascular system is emerging along with the recognition
that it is required for normal cellular function and homeostasis. Consequently,
the impact of changes in O-GlcNAc cycling due to stress or disease on the heart
is complex and highly dependent on the specific context of these events. The goal
of this review is to provide an overview of some of the more recent advances in
our understanding of the role O-GlcNAcylation plays in mediating cardiovascular
function and disease.
PMID- 28408496
TI - Visualizing the life of mRNA in T cells.
AB - T cells release ample amounts of cytokines during infection. This property is
critical to prevent pathogen spreading and persistence. Nevertheless, whereas
rapid and ample cytokine production supports the clearance of pathogens, the
production must be restricted in time and location to prevent detrimental effects
of chronic inflammation and immunopathology. Transcriptional and post
transcriptional processes determine the levels of cytokine production. How these
regulatory mechanisms are interconnected, and how they regulate the magnitude of
protein production in primary T cells is to date not well studied. Here, we
highlight recent advances in the field that boost our understanding of the
regulatory processes of cytokine production of T cells, with a focus on
transcription, mRNA stability, localization and translation.
PMID- 28408498
TI - Correction: Biogenesis and activity regulation of protein phosphatase 1.
PMID- 28408497
TI - Iminosugar antivirals: the therapeutic sweet spot.
AB - Many viruses require the host endoplasmic reticulum protein-folding machinery in
order to correctly fold one or more of their glycoproteins. Iminosugars with
glucose stereochemistry target the glucosidases which are key for entry into the
glycoprotein folding cycle. Viral glycoproteins are thus prevented from
interacting with the protein-folding machinery leading to misfolding and an
antiviral effect against a wide range of different viral families. As iminosugars
target host enzymes, they should be refractory to mutations in the virus.
Iminosugars therefore have great potential for development as broad-spectrum
antiviral therapeutics. We outline the mechanism giving rise to the antiviral
activity of iminosugars, the current progress in the development of iminosugar
antivirals and future prospects for this field.
PMID- 28408508
TI - Incorrect details on microchip databases mean stray dogs remain unclaimed.
PMID- 28408509
TI - Hydatid disease: making a comeback?
AB - Hydatid disease is re-emerging in the British Isles, with cases being found
across the country. As John Bonner reports, the consequences could be far
reaching.
PMID- 28408510
TI - Vet students help regiments declare their horses to be 'strangles free'.
PMID- 28408511
TI - Balancing responsibilities when prescribing antimicrobials for farm animals.
PMID- 28408513
TI - BestBETs for Vets.
AB - BestBETs for Vets are generated by the Centre for Evidence-based Veterinary
Medicine at the University of Nottingham to help answer specific questions and
assist in clinical decision making. Although evidence is often limited, they aim
to find, present and draw conclusions from the best available evidence, using a
standardised framework. A more detailed description of how BestBETs for Vets are
produced was published in a previous issue of Veterinary Record (VR, April 4,
2015, pp 354-356).
PMID- 28408514
TI - Robenacoxib for acute musculoskeletal pain control in cats.
PMID- 28408516
TI - Brucella canis in a dog in the UK.
PMID- 28408519
TI - Survey on updating OIE World Animal Health Information System.
PMID- 28408518
TI - Neutering of pet rabbits.
PMID- 28408520
TI - In or out . . . is there a dilemma for cat welfare?
PMID- 28408524
TI - Developing tomorrow's vets today.
AB - Darren Mackintosh, operations manager at Independent Vetcare, explains why the
group has developed an EMS scheme.
PMID- 28408525
TI - Rosie's diary.
AB - Every month, Vet Record Careers checks in with third-year vet student Rosie
Perrett.
PMID- 28408526
TI - 68Ga or 18F for Prostate Cancer Imaging?
PMID- 28408527
TI - The Future of Radioligand Therapy: alpha, beta, or Both?
PMID- 28408528
TI - Cerenkov Radiation-Induced Photoimmunotherapy with 18F-FDG.
AB - Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that
combines the specificity of antibodies for targeting tumors with toxicity induced
by photoabsorbers after irradiation with NIR light. A limitation of NIR-PIT is
the inability to deliver NIR light to a tumor located deep inside the body.
Cerenkov radiation (CR) is the ultraviolet and blue light that is produced by a
charged particle traveling through a dielectric medium faster than the speed of
light in that medium and is commonly produced during radioactive decay. Here, we
demonstrate the feasibility of using CR generated by 18F-FDG accumulated in
tumors to induce photoimmunotherapy. Methods: Using A431-luc cells, we evaluated
the therapeutic effects of CR-PIT in vitro and in vivo using bioluminescence
imaging. Results: CR-PIT showed significant suppression of tumor size, but the
decrease of bioluminescence after CR-PIT was not observed consistently over the
entire time course. Conclusion: Although CR-PIT can induce tumor killing deep
within body, it is less effective than NIR-PIT, possibly related to the
relatively lower efficiency of short wavelength light than NIR.
PMID- 28408529
TI - Targeted alpha-Therapy of Metastatic Castration-Resistant Prostate Cancer with
225Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding.
AB - The aim of this study was to develop a treatment protocol for 225Ac-PSMA-617
alpha-radiation therapy in advanced-stage, metastatic castration-resistant
prostate cancer patients with prostate-specific membrane antigen (PSMA)-positive
tumor phenotype. Methods: A dosimetry estimate was calculated on the basis of
time-activity curves derived from serially obtained 177Lu-PSMA-617 scans
extrapolated to the physical half-life of 225Ac, assuming instant decay of
unstable daughter nuclides. Salvage therapies empirically conducted with 50 (n =
4), 100 (n = 4), 150 (n = 2), and 200 kBq/kg (n = 4) of 225Ac-PSMA-617 were
evaluated retrospectively regarding toxicity and treatment response. Eight of 14
patients received further cycles in either 2- or 4-mo intervals with identical or
deescalated activities. Results: Dosimetry estimates for 1 MBq of 225Ac-PSMA-617
assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for
salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed
of 99.4% alpha, 0.5% beta, and 0.1% photon radiation, respectively. In clinical
application, severe xerostomia became the dose-limiting toxicity if treatment
activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate
specific antigen decline was less than 4 mo, but if therapy was repeated every 2
mo patients experienced additive antitumor effects. Treatment activities of 50
kBq/kg were without toxicity but induced insufficient antitumor response in these
high-tumor-burden patients. Remarkable antitumor activity by means of objective
radiologic response or tumor marker decline was observed in 9 of 11 evaluable
patients. Conclusion: For advanced-stage patients, a treatment activity of 100
kBq/kg of 225Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable
trade-off between toxicity and biochemical response.
PMID- 28408530
TI - Alternative Means of Estimating 131I Maximum Permissible Activity to Treat
Thyroid Cancer.
AB - To protect bone marrow from overirradiation, the maximum permissible activity
(MPA) of 131I to treat thyroid cancer is that which limits the absorbed dose to
blood (as a surrogate of marrow) to less than 200 cGy. The conventional approach
(method 1) requires repeated gamma-camera whole-body measurements along with
blood samples. We sought to determine whether reliable MPA values can be obtained
by simplified procedures. Methods: Data acquired over multiple time points were
examined retrospectively for 65 thyroid cancer patients, referred to determine
131I uptake and MPA for initial treatment after thyroidectomy (n = 39), including
17 patients with compromised renal function and 22 patients with known (n = 16)
or suspected (n = 6) metastases. The total absorbed dose to blood (DTotal) was
the sum of mean whole-body gamma-ray dose component (Dgamma) from uncollimated
gamma-camera measurements and dose due to beta emissions (Dbeta) from blood
samples. Method 2 estimated DTotal from Dbeta alone, method 3 estimated DTotal
from Dgamma alone, and method 4 estimated DTotal from a single 48-h gamma-camera
measurement. MPA was computed as 200 cGy/DTotal for each DTotal estimate.
Results: Method 2 had the strongest correlation with conventional method 1 (r =
0.98) and values similar to method 1 (21.0 +/- 13.7 cGy/GBq vs. 21.0 +/- 14.1
cGy/GBq, P = 0.11), whereas method 3 had a weaker (P = 0.001) correlation (r =
0.94) and method 4 had the weakest (P < 0.0001) correlation (r = 0.69) and lower
dose (16.3 +/- 14.8 cGy/GBq, P < 0.0001). Consequently, correlation with method 1
MPA was strongest for method 2 MPA (r = 0.99) and weakest for method 4 (r = 0.
75). Method 2 and method 1 values agreed equally well regardless of whether
patients had been treated with 131I previously or had abnormal renal function.
Conclusion: Because MPA based on blood measurements alone is comparable to MPA
obtained with combined body counting and blood sampling, blood measurements alone
are sufficient for determining MPA.
PMID- 28408531
TI - 68Ga-PSMA-11 PET/CT Interobserver Agreement for Prostate Cancer Assessments: An
International Multicenter Prospective Study.
AB - The interobserver agreement for 68Ga-PSMA-11 PET/CT study interpretations in
patients with prostate cancer is unknown. Methods:68Ga-PSMA-11 PET/CT was
performed in 50 patients with prostate cancer for biochemical recurrence (n =
25), primary diagnosis (n = 10), biochemical persistence after primary therapy (n
= 5), or staging of known metastatic disease (n = 10). Images were reviewed by 16
observers who used a standardized approach for interpretation of local (T), nodal
(N), bone (Mb), or visceral (Mc) involvement. Observers were classified as having
a low (<30 prior 68Ga-PSMA-11 PET/CT studies; n = 5), intermediate (30-300
studies; n = 5), or high level of experience (>300 studies; n = 6).
Histopathology (n = 25, 50%), post-external-beam radiation therapy prostate
specific antigen response (n = 15, 30%), or follow-up PET/CT (n = 10, 20%) served
as a standard of reference. Observer groups were compared by overall agreement (%
patients matching the standard of reference) and Fleiss' kappa with mean and
corresponding 95% confidence interval (CI). Results: Agreement among all
observers was substantial for T (kappa = 0.62; 95% CI, 0.59-0.64) and N (kappa =
0.74; 95% CI, 0.71-0.76) staging and almost perfect for Mb (kappa = 0.88; 95% CI,
0.86-0.91) staging. Level of experience positively correlated with agreement for
T (kappa = 0.73/0.66/0.50 for high/intermediate/low experience, respectively), N
(kappa = 0.80/0.76/0.64, respectively), and Mc staging (kappa = 0.61/0.46/0.36,
respectively). Interobserver agreement for Mb was almost perfect irrespective of
prior experience (kappa = 0.87/0.91/0.88, respectively). Observers with low
experience, when compared with intermediate and high experience, demonstrated
significantly lower median overall agreement (54% vs. 66% and 76%, P = 0.041) and
specificity for T staging (73% vs. 88% and 93%, P = 0.032). Conclusion: The
interpretation of 68Ga-PSMA-11 PET/CT for prostate cancer staging is highly
consistent among observers with high levels of experience, especially for nodal
and bone assessments. Initial training on at least 30 patient cases is
recommended to ensure acceptable performance.
PMID- 28408534
TI - The mission lifeline severity-based stroke treatment algorithm: We need more
time.
PMID- 28408532
TI - 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room
Temperature, 1-Step Kit-Based Radiolabeling.
AB - The clinical impact and accessibility of 68Ga tracers for the prostate-specific
membrane antigen (PSMA) and other targets would be greatly enhanced by the
availability of a simple, 1-step kit-based labeling process. Radiopharmacy staff
are accustomed to such procedures in the daily preparation of 99mTc
radiopharmaceuticals. Currently, chelating agents used in 68Ga
radiopharmaceuticals do not meet this ideal. The aim of this study was to develop
and evaluate preclinically a 68Ga radiotracer for imaging PSMA expression that
could be radiolabeled simply by addition of 68Ga generator eluate to a cold kit.
Methods: A conjugate of a tris(hydroxypyridinone) (THP) chelator with the
established urea-based PSMA inhibitor was synthesized and radiolabeled with 68Ga
by adding generator eluate directly to a vial containing the cold precursors THP
PSMA and sodium bicarbonate, with no further manipulation. It was analyzed after
5 min by instant thin-layer chromatography and high-performance liquid
chromatography. The product was subjected to in vitro studies to determine PSMA
affinity using PSMA-expressing DU145-PSMA cells, with their nonexpressing analog
DU145 as a control. In vivo PET imaging and ex vivo biodistribution studies were
performed in mice bearing xenografts of the same cell lines, comparing 68Ga-THP
PSMA with 68Ga-HBED-CC-PSMA. Results: Radiolabeling was complete (>95%) within 5
min at room temperature, showing a single radioactive species by high-performance
liquid chromatography that was stable in human serum for more than 6 h and showed
specific binding to PSMA-expressing cells (concentration giving 50% inhibition of
361 +/- 60 nM). In vivo PET imaging showed specific uptake in PSMA-expressing
tumors, reaching 5.6 +/- 1.2 percentage injected dose per cubic centimeter at 40
60 min and rapid clearance from blood to kidney and bladder. The tumor uptake,
biodistribution, and pharmacokinetics were not significantly different from those
of 68Ga-HBED-CC-PSMA except for reduced uptake in the spleen. Conclusion:68Ga-THP
PSMA has equivalent imaging properties but greatly simplified radiolabeling
compared with other 68Ga-PSMA conjugates. THP offers the prospect of rapid,
simple, 1-step, room-temperature syringe-and-vial radiolabeling of 68Ga
radiopharmaceuticals.
PMID- 28408533
TI - Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That
Thermoresponsively Self-Aggregate in Tumor Tissues.
AB - Brachytherapy is a type of radiotherapy wherein titanium capsules containing
therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose
radioirradiation to tumor tissues around the seeds. Although marked therapeutic
effects have been demonstrated, brachytherapy needs a complicated implantation
technique under general anesthesia and the seeds could migrate to other organs.
The aim of this study was to establish a novel brachytherapy using biocompatible,
injectable thermoresponsive polymers (polyoxazoline [POZ]) labeled with 90Y,
which can self-aggregate above a specific transition temperature (Tt), resulting
in long-term intratumoral retention of radioactivity and therapeutic effect.
Therefore, we evaluated the tumor retention of radiolabeled POZ derivatives and
their therapeutic effects. Methods: Using oxazoline derivatives with ethyl (Et),
isopropyl (Isp), and propyl (Pr) side chains, we synthesized EtPOZ, IspPOZ, Isp
PrPOZ (heteropolymer), and PrPOZ and measured their characteristic Tts. The
intratumoral retention of 111In-labeled POZ was evaluated until 7 d after
injection in nude mice bearing PC-3 human prostate cancer. The intratumoral
localization of 111In-labeled POZ derivatives was investigated by an
autoradiographic study. Furthermore, a therapeutic study using 90Y-labeled Isp
PrPOZ was performed, and tumor growth and survival rate were evaluated. Results:
The Tts of EtPOZ, IspPOZ, Isp-PrPOZ, and PrPOZ (~20 kDa) were greater than 70
degrees C, 34 degrees C, 25 degrees C, and 19 degrees C, respectively. In the
intratumoral injection study, Isp-PrPOZ and PrPOZ (2,000 MUM) with Tts lower than
tumor temperature (33.5 degrees C under anesthesia) showed a significantly higher
retention of radioactivity at 1 d after injection (73.6% and 73.9%, respectively)
than EtPOZ (5.6%) and IspPOZ (15.8%). Even at low injected dose (100 MUM), Isp
PrPOZ exhibited high retention (68.3% at 1 d). The high level of radioactivity of
Isp-PrPOZ was retained in the tumor 7 d after injection (69.5%). The
autoradiographic study demonstrated that the radioactivity of 111In-labeled Isp
PrPOZ and PrPOZ was localized in a small area. In the therapeutic study using 90Y
labeled Isp-PrPOZ, significant suppression of tumor growth and prolonged survival
rate were achieved in an injection dose-dependent manner compared with that
observed for the vehicle-injected group and nonradioactive Isp-PrPOZ-injected
group. Conclusion: The injectable 90Y-labeled Isp-PrPOZ was retained for a
prolonged period within tumor tissues via self-aggregation and exhibited marked
therapeutic effect, suggesting its usefulness for brachytherapy.
PMID- 28408535
TI - Unconscious bias must be tackled to reduce worry about overseas trained doctors,
says BAPIO.
PMID- 28408536
TI - Rectus sheath haematoma: a rare masquerader for abdominal pain.
AB - Rectus sheath haematoma is a rare cause of abdominal pain. It can be easily
confused for other causes of acute abdomen and may even lead to unnecessary
laparotomies. Our patient has the rectus sheath haematoma because of violent
coughing and on presentation had no obvious clinical sign pointing to the same.
Diagnosis was made by a CT scan of the abdomen, and patient was treated
conservatively. Rectus sheath haematomas are usually present on the posterior
aspect of the rectus muscles and thus may not be clinically appreciable.
PMID- 28408537
TI - Postpartum tubo-ovarian abscess, likely arising from pelvic inflammatory disease
during pregnancy.
PMID- 28408538
TI - Medical devices face tougher premarket testing under new EU laws.
PMID- 28408540
TI - Small kernel2 Encodes a Glutaminase in Vitamin B6 Biosynthesis Essential for
Maize Seed Development.
AB - Vitamin B6, an essential cofactor for a range of biochemical reactions and a
potent antioxidant, plays important roles in plant growth, development, and
stress tolerance. Vitamin B6 deficiency causes embryo lethality in Arabidopsis
(Arabidopsis thaliana), but the specific role of vitamin B6 biosynthesis in
endosperm development has not been fully addressed, especially in monocot crops,
where endosperm constitutes the major portion of the grain. Through molecular
characterization of a small kernel2 (smk2) mutant in maize, we reveal that
vitamin B6 has differential effects on embryogenesis and endosperm development in
maize. The B6 vitamer pyridoxal 5'-phosphate (PLP) is drastically reduced in both
the smk2 embryo and the endosperm. However, whereas embryogenesis of the smk2
mutant is arrested at the transition stage, endosperm formation is nearly normal.
Cloning reveals that Smk2 encodes the glutaminase subunit of the PLP synthase
complex involved in vitamin B6 biosynthesis de novo. Smk2 partially complements
the Arabidopsis vitamin B6-deficient mutant pdx2.1 and Saccharomyces cerevisiae
pyridoxine auxotrophic mutant MML21. Smk2 is constitutively expressed in the
maize plant, including developing embryos. Analysis of B6 vitamers indicates that
the endosperm accumulates a large amount of pyridoxamine 5'-phosphate (PMP).
These results indicate that vitamin B6 is essential to embryogenesis but has a
reduced role in endosperm development in maize. The vitamin B6 required for seed
development is synthesized in the seed, and the endosperm accumulates PMP
probably as a storage form of vitamin B6.
PMID- 28408541
TI - Night-Break Experiments Shed Light on the Photoperiod1-Mediated Flowering.
AB - Plants utilize variation in day length (photoperiod) to anticipate seasonal
changes. They respond by modulating their growth and development to maximize seed
production, which in cereal crops is directly related to yield. In wheat
(Triticum aestivum), the acceleration of flowering under long days (LD) is
dependent on the light induction of PHOTOPERIOD1 (PPD1) by phytochromes. Under
LD, PPD1 activates FLOWERING LOCUS T1 (FT1), a mobile signaling protein that
travels from the leaves to the shoot apical meristem to promote flowering. Here,
we show that the interruption of long nights by short pulses of light ("night
break" [NB]) accelerates wheat flowering, suggesting that the duration of the
night is critical for wheat photoperiodic response. PPD1 transcription was
rapidly upregulated by NBs, and the magnitude of this induction increased with
the length of darkness preceding the NB Cycloheximide abolished the NB up
regulation of PPD1, suggesting that this process is dependent on active protein
synthesis during darkness. While one NB was sufficient to induce PPD1, more than
15 NBs were required to induce high levels of FT1 expression and a strong
acceleration of flowering. Multiple NBs did not affect the expression of core
circadian clock genes. The acceleration of flowering by NB disappeared in ppd1
null mutants, demonstrating that this response is mediated by PPD1 The
acceleration of flowering was strongest when NBs were applied in the middle of
the night, suggesting that in addition to PPD1, other circadian-controlled
factors are required for the up-regulation of FT1 expression and the acceleration
of flowering.
PMID- 28408542
TI - Acyl-CoA:Lysophosphatidylethanolamine Acyltransferase Activity Regulates Growth
of Arabidopsis.
AB - Arabidopsis (Arabidopsis thaliana) contains two enzymes (encoded by the At1g80950
and At2g45670 genes) preferentially acylating lysophosphatidylethanolamine (LPE)
with acyl-coenzyme A (CoA), designated LYSOPHOSPHATIDYLETHANOLAMINE
ACYLTRANSFERASE1 (LPEAT1) and LPEAT2. The transfer DNA insertion mutant lpeat2
and the double mutant lpeat1 lpeat2 showed impaired growth, smaller leaves,
shorter roots, less seed setting, and reduced lipid content per fresh weight in
roots and seeds and large increases in LPE and lysophosphatidylcholine (LPC)
contents in leaves. Microsomal preparations from leaves of these mutants showed
around 70% decrease in acylation activity of LPE with 16:0-CoA compared with wild
type membranes, whereas the acylation with 18:1-CoA was much less affected,
demonstrating that other lysophospholipid acyltransferases than the two LPEATs
could acylate LPE The above-mentioned effects were less pronounced in the single
lpeat1 mutant. Overexpression of either LPEAT1 or LPEAT2 under the control of the
35S promotor led to morphological changes opposite to what was seen in the
transfer DNA mutants. Acyl specificity studies showed that LPEAT1 utilized 16:0
CoA at the highest rate of 11 tested acyl-CoAs, whereas LPEAT2 utilized 20:0-CoA
as the best acyl donor. Both LPEATs could acylate either sn position of ether
analogs of LPC The data show that the activities of LPEAT1 and LPEAT2 are, in a
complementary way, involved in growth regulation in Arabidopsis. It is shown that
LPEAT activity (especially LPEAT2) is essential for maintaining adequate levels
of phosphatidylethanolamine, LPE, and LPC in the cells.
PMID- 28408543
TI - Determinants of institutional delivery among young married women in Nepal:
Evidence from the Nepal Demographic and Health Survey, 2011.
AB - OBJECTIVES: To identify the determinants of institutional delivery among young
married women in Nepal. DESIGN: Nepal Demographic and Health Survey (NDHS) data
sets 2011 were analysed. Bivariate and multivariate logistic regression analyses
were performed using a subset of 1662 ever-married young women (aged 15-24
years). OUTCOME MEASURE: Place of delivery. RESULTS: The rate of institutional
delivery among young married women was 46%, which is higher than the national
average (35%) among all women of reproductive age. Young women who had more than
four antenatal care (ANC) visits were three times more likely to deliver in a
health institution compared with women who had no antenatal care visit (OR: 3.05;
95% CI: 2.40 to 3.87). The probability of delivering in an institution was 69%
higher among young urban women than among young women who lived in rural areas.
Young women who had secondary or above secondary level education were 1.63 times
more likely to choose institutional delivery than young women who had no formal
education (OR: 1.626; 95% CI: 1.171 to 2.258). Lower use of a health institution
for delivery was also observed among poor young women. Results showed that
wealthy young women were 2.12 times more likely to deliver their child in an
institution compared with poor young women (OR: 2.107; 95% CI: 1.53 to 2.898).
Other factors such as the age of the young woman, religion, ethnicity, and
ecological zone were also associated with institutional delivery. CONCLUSIONS:
Maternal health programs should be designed to encourage young women to receive
adequate ANC (at least four visits). Moreover, health programs should target
poor, less educated, rural, young women who live in mountain regions, are of
Janajati ethnicity and have at least one child as such women are less likely to
choose institutional delivery in Nepal.
PMID- 28408544
TI - Cost and outcome of behavioural activation versus cognitive behavioural therapy
for depression (COBRA): a qualitative process evaluation.
AB - OBJECTIVE: To explore participant views on acceptability, mechanisms of change
and impact of behavioural activation (BA) delivered by junior mental health
workers (MHWs) versus cognitive behavioural therapy (CBT) delivered by
professional psychotherapists. DESIGN: Semistructured qualitative interviews
analysed using a framework approach. PARTICIPANTS: 36 participants with major
depressive disorder purposively sampled from a randomised controlled trial of BA
versus CBT (the COBRA trial). SETTING: Primary care psychological therapies
services in Devon, Durham and Leeds, UK. RESULTS: Elements of therapy considered
to be beneficial included its length and regularity, the opportunity to learn and
not dwelling on the past. Homework was an important, although challenging aspect
of treatment. Therapists were perceived as experts who played an important role
in treatment. For some participants the most important element of therapy was
having someone to talk to, but for others the specific factors associated with BA
and CBT were crucial, with behavioural change considered important for
participants in both treatments, and cognitive change unsurprisingly discussed
more by those receiving CBT. Both therapies were considered to have a positive
impact on symptoms of depression and other areas of life including feelings about
themselves, self-care, work and relationships. Barriers to therapy included work,
family life and emotional challenges. A subset (n=2) of BA participants commented
that therapy felt too simple, and MHWs could be perceived as inexperienced. Many
participants saw therapy as a learning experience, providing them with tools to
take away, with work on relapse prevention essential. CONCLUSIONS: Despite
barriers for some participants, BA and CBT were perceived to have many benefits,
to have brought about cognitive and behavioural change and to produce
improvements in many domains of participants' lives. To optimise the delivery of
BA, inexperienced junior MHWs should be supported through good quality training
and ongoing supervision. TRIAL REGISTRATION NUMBER: ISRCTN27473954, 09/12/2011.
PMID- 28408539
TI - The Membrane Transport System of the Guard Cell and Its Integration for Stomatal
Dynamics.
AB - Stomatal guard cells are widely recognized as the premier plant cell model for
membrane transport, signaling, and homeostasis. This recognition is rooted in
half a century of research into ion transport across the plasma and vacuolar
membranes of guard cells that drive stomatal movements and the signaling
mechanisms that regulate them. Stomatal guard cells surround pores in the
epidermis of plant leaves, controlling the aperture of the pore to balance CO2
entry into the leaf for photosynthesis with water loss via transpiration. The
position of guard cells in the epidermis is ideally suited for cellular and
subcellular research, and their sensitivity to endogenous signals and
environmental stimuli makes them a primary target for physiological studies.
Stomata underpin the challenges of water availability and crop production that
are expected to unfold over the next 20 to 30 years. A quantitative understanding
of how ion transport is integrated and controlled is key to meeting these
challenges and to engineering guard cells for improved water use efficiency and
agricultural yields.
PMID- 28408546
TI - Transition metal-catalyzed alkyl-alkyl bond formation: Another dimension in cross
coupling chemistry.
AB - Because the backbone of most organic molecules is composed primarily of carbon
carbon bonds, the development of efficient methods for their construction is one
of the central challenges of organic synthesis. Transition metal-catalyzed cross
coupling reactions between organic electrophiles and nucleophiles serve as
particularly powerful tools for achieving carbon-carbon bond formation. Until
recently, the vast majority of cross-coupling processes had used either aryl or
alkenyl electrophiles as one of the coupling partners. In the past 15 years,
versatile new methods have been developed that effect cross-couplings of an array
of alkyl electrophiles, thereby greatly expanding the diversity of target
molecules that are readily accessible. The ability to couple alkyl electrophiles
opens the door to a stereochemical dimension-specifically, enantioconvergent
couplings of racemic electrophiles-that substantially enhances the already
remarkable utility of cross-coupling processes.
PMID- 28408545
TI - Reducing Medical Admissions into Hospital through Optimising Medicines (REMAIN
HOME) Study: protocol for a stepped-wedge, cluster-randomised trial.
AB - INTRODUCTION: A model of general practitioner (GP) and pharmacist collaboration
in primary care may be an effective strategy to reduce medication-related
problems and provide better support to patients after discharge. The aim of this
study is to investigate whether a model of structured pharmacist and GP care
reduces hospital readmissions in high-risk patients. METHODS AND ANALYSIS: This
protocol details a stepped-wedge, cluster-randomised trial that will recruit
participants over 9 months with a 12-month follow-up. There will be 14 clusters
each representing a different general practice medical centre. A total of 2240
participants will be recruited from hospital who attend an enrolled medical
centre, take five or more long-term medicines or whose reason for admission was
related to heart failure or chronic obstructive pulmonary disease.The
intervention is a multifaceted service, involving a pharmacist integrated into a
medical centre to assist patients after hospitalisation. Participants will meet
with the practice pharmacist and their GP after discharge to review and reconcile
their medicines and discuss changes made in hospital. The pharmacist will follow
up with the participant and liaise with other health professionals involved in
the participant's care. The control will be usual care, which usually involves a
patient self-organising a visit to their GP after hospital discharge.The primary
outcome is the rate of unplanned, all-cause hospital readmissions over 12 months,
which will be analysed using a mixed effects Poisson regression model with a
random effect for cluster and a fixed effect to account for any temporal trend. A
cost analysis will be undertaken to compare the healthcare costs associated with
the intervention to those of usual care. ETHICS AND DISSEMINATION: The study has
received ethical approval (HREC/16/QRBW/410). The study findings will be
disseminated through peer-reviewed publications, conferences and reports to key
stakeholders. TRIAL REGISTRATION NUMBER: ACTRN12616001627448.
PMID- 28408547
TI - News at a glance.
PMID- 28408548
TI - On eve of science march, planners look ahead.
PMID- 28408549
TI - Why the rest of the world is marching.
PMID- 28408550
TI - Cassini embarks on twilight mission at Saturn.
PMID- 28408551
TI - Food for microbes abundant on Enceladus.
PMID- 28408552
TI - Personalized tumor vaccines keep cancer in check.
PMID- 28408553
TI - U.S. report calls for research integrity board.
PMID- 28408554
TI - Giant radio telescope faces downsizing.
PMID- 28408555
TI - Epidemic Insurance.
PMID- 28408556
TI - The Weather Master.
PMID- 28408557
TI - Detecting molecular hydrogen on Enceladus.
PMID- 28408558
TI - An AI stereotype catcher.
PMID- 28408559
TI - Allotropy by design-Carbon nanohoops.
PMID- 28408560
TI - Eating ecosystems.
PMID- 28408561
TI - Embryogenesis in a dish.
PMID- 28408562
TI - Managing cell and human identity.
PMID- 28408564
TI - Embracing the unqualified opinion.
PMID- 28408563
TI - Terawatt-scale photovoltaics: Trajectories and challenges.
PMID- 28408565
TI - A river runs through it.
PMID- 28408567
TI - March for Science: Share your sign.
PMID- 28408566
TI - After Chile's fires, reforest private land.
PMID- 28408569
TI - Targeting nonviral antigens in viral-driven cancer.
PMID- 28408568
TI - Europe's insufficient pollutant remediation.
PMID- 28408570
TI - Hydrothermal processes on Enceladus.
PMID- 28408571
TI - Transporter layers for greater stability.
PMID- 28408572
TI - Stitching a belt out of carbon rings.
PMID- 28408573
TI - One antibody for all and all antibodies for one.
PMID- 28408574
TI - Nucleosomes in contact.
PMID- 28408576
TI - A target for preventing kidney damage.
PMID- 28408575
TI - Quantifying hunting-induced defaunation.
PMID- 28408577
TI - The negative impact of EU enlargement.
PMID- 28408579
TI - An earthquake with a dozen faults.
PMID- 28408578
TI - Stitching one alkyl group to another.
PMID- 28408580
TI - In vitro embryogenesis.
PMID- 28408581
TI - Crustal rock strength from outer space.
PMID- 28408582
TI - Machines learn what people know implicitly.
PMID- 28408583
TI - Refined understanding of the preprophase band.
PMID- 28408584
TI - Making an unbiased library.
PMID- 28408585
TI - Coupling transcription and translation.
PMID- 28408586
TI - How the flagellum knows when to stop.
PMID- 28408587
TI - The evolving Ebola virus host response.
PMID- 28408589
TI - Regulatory T cells sans FoxP3.
PMID- 28408588
TI - Adding a twist for enhanced performance.
PMID- 28408590
TI - Heavy metals? No problem for this snail.
PMID- 28408591
TI - Near and far effects on gene expression.
PMID- 28408592
TI - TB exploits zombie cells.
PMID- 28408593
TI - Protectin and resolvin gut inflammation.
PMID- 28408594
TI - Mixing up isotopes in evolved stars.
PMID- 28408595
TI - Smashing ions to test a theory.
PMID- 28408596
TI - YAP is crucial for lung branching morphogenesis.
PMID- 28408597
TI - Cassini finds molecular hydrogen in the Enceladus plume: Evidence for
hydrothermal processes.
AB - Saturn's moon Enceladus has an ice-covered ocean; a plume of material erupts from
cracks in the ice. The plume contains chemical signatures of water-rock
interaction between the ocean and a rocky core. We used the Ion Neutral Mass
Spectrometer onboard the Cassini spacecraft to detect molecular hydrogen in the
plume. By using the instrument's open-source mode, background processes of
hydrogen production in the instrument were minimized and quantified, enabling the
identification of a statistically significant signal of hydrogen native to
Enceladus. We find that the most plausible source of this hydrogen is ongoing
hydrothermal reactions of rock containing reduced minerals and organic materials.
The relatively high hydrogen abundance in the plume signals thermodynamic
disequilibrium that favors the formation of methane from CO2 in Enceladus' ocean.
PMID- 28408598
TI - Imaging the distribution of transient viscosity after the 2016 Mw 7.1 Kumamoto
earthquake.
AB - The deformation of mantle and crustal rocks in response to stress plays a crucial
role in the distribution of seismic and volcanic hazards, controlling tectonic
processes ranging from continental drift to earthquake triggering. However, the
spatial variation of these dynamic properties is poorly understood as they are
difficult to measure. We exploited the large stress perturbation incurred by the
2016 earthquake sequence in Kumamoto, Japan, to directly image localized and
distributed deformation. The earthquakes illuminated distinct regions of low
effective viscosity in the lower crust, notably beneath the Mount Aso and Mount
Kuju volcanoes, surrounded by larger-scale variations of viscosity across the
back-arc. This study demonstrates a new potential for geodesy to directly probe
rock rheology in situ across many spatial and temporal scales.
PMID- 28408599
TI - Synthesis of a carbon nanobelt.
AB - The synthesis of a carbon nanobelt, comprising a closed loop of fully fused edge
sharing benzene rings, has been an elusive goal in organic chemistry for more
than 60 years. Here we report the synthesis of one such compound through
iterative Wittig reactions followed by a nickel-mediated aryl-aryl coupling
reaction. The cylindrical shape of its belt structure was confirmed by x-ray
crystallography, and its fundamental optoelectronic properties were elucidated by
ultraviolet-visible absorption, fluorescence, and Raman spectroscopic studies, as
well as theoretical calculations. This molecule could potentially serve as a seed
for the preparation of structurally well-defined carbon nanotubes.
PMID- 28408600
TI - The impact of hunting on tropical mammal and bird populations.
AB - Hunting is a major driver of biodiversity loss, but a systematic large-scale
estimate of hunting-induced defaunation is lacking. We synthesized 176 studies to
quantify hunting-induced declines of mammal and bird populations across the
tropics. Bird and mammal abundances declined by 58% (25 to 76%) and by 83% (72 to
90%) in hunted compared with unhunted areas. Bird and mammal populations were
depleted within 7 and 40 kilometers from hunters' access points (roads and
settlements). Additionally, hunting pressure was higher in areas with better
accessibility to major towns where wild meat could be traded. Mammal population
densities were lower outside protected areas, particularly because of commercial
hunting. Strategies to sustainably manage wild meat hunting in both protected and
unprotected tropical ecosystems are urgently needed to avoid further defaunation.
PMID- 28408601
TI - Semantics derived automatically from language corpora contain human-like biases.
AB - Machine learning is a means to derive artificial intelligence by discovering
patterns in existing data. Here, we show that applying machine learning to
ordinary human language results in human-like semantic biases. We replicated a
spectrum of known biases, as measured by the Implicit Association Test, using a
widely used, purely statistical machine-learning model trained on a standard
corpus of text from the World Wide Web. Our results indicate that text corpora
contain recoverable and accurate imprints of our historic biases, whether morally
neutral as toward insects or flowers, problematic as toward race or gender, or
even simply veridical, reflecting the status quo distribution of gender with
respect to careers or first names. Our methods hold promise for identifying and
addressing sources of bias in culture, including technology.
PMID- 28408602
TI - The preprophase band of microtubules controls the robustness of division
orientation in plants.
AB - Controlling cell division plane orientation is essential for morphogenesis in
multicellular organisms. In plant cells, the future cortical division plane is
marked before mitotic entry by the preprophase band (PPB). Here, we characterized
an Arabidopsis trm (TON1 Recruiting Motif) mutant that impairs PPB formation but
does not affect interphase microtubules. Unexpectedly, PPB disruption neither
abolished the capacity of root cells to define a cortical division zone nor
induced aberrant cell division patterns but rather caused a loss of precision in
cell division orientation. Our results advocate for a reassessment of PPB
function and division plane determination in plants and show that a main output
of this microtubule array is to limit spindle rotations in order to increase the
robustness of cell division.
PMID- 28408603
TI - Single-cell whole-genome analyses by Linear Amplification via Transposon
Insertion (LIANTI).
AB - Single-cell genomics is important for biology and medicine. However, current
whole-genome amplification (WGA) methods are limited by low accuracy of copy
number variation (CNV) detection and low amplification fidelity. Here we report
an improved single-cell WGA method, Linear Amplification via Transposon Insertion
(LIANTI), which outperforms existing methods, enabling micro-CNV detection with
kilobase resolution. This allowed direct observation of stochastic firing of DNA
replication origins, which differs from cell to cell. We also show that the
predominant cytosine-to-thymine mutations observed in single-cell genomics often
arise from the artifact of cytosine deamination upon cell lysis. However,
identifying single-nucleotide variations (SNVs) can be accomplished by sequencing
kindred cells. We determined the spectrum of SNVs in a single human cell after
ultraviolet radiation, revealing their nonrandom genome-wide distribution.
PMID- 28408604
TI - Architecture of a transcribing-translating expressome.
AB - DNA transcription is functionally coupled to messenger RNA (mRNA) translation in
bacteria, but how this is achieved remains unclear. Here we show that RNA
polymerase (RNAP) and the ribosome of Escherichia coli can form a defined
transcribing and translating "expressome" complex. The cryo-electron microscopic
structure of the expressome reveals continuous protection of ~30 nucleotides of
mRNA extending from the RNAP active center to the ribosome decoding center. The
RNAP-ribosome interface includes the RNAP subunit alpha carboxyl-terminal domain,
which is required for RNAP-ribosome interaction in vitro and for pronounced cell
growth defects upon translation inhibition in vivo, consistent with its function
in transcription-translation coupling. The expressome structure can only form
during transcription elongation and explains how translation can prevent
transcriptional pausing, backtracking, and termination.
PMID- 28408605
TI - Nanoscale-length control of the flagellar driveshaft requires hitting the
tethered outer membrane.
AB - The bacterial flagellum exemplifies a system where even small deviations from the
highly regulated flagellar assembly process can abolish motility and cause
negative physiological outcomes. Consequently, bacteria have evolved elegant and
robust regulatory mechanisms to ensure that flagellar morphogenesis follows a
defined path, with each component self-assembling to predetermined dimensions.
The flagellar rod acts as a driveshaft to transmit torque from the cytoplasmic
rotor to the external filament. The rod self-assembles to a defined length of ~25
nanometers. Here, we provide evidence that rod length is limited by the width of
the periplasmic space between the inner and outer membranes. The length of
Braun's lipoprotein determines periplasmic width by tethering the outer membrane
to the peptidoglycan layer.
PMID- 28408606
TI - Landscape of immunogenic tumor antigens in successful immunotherapy of virally
induced epithelial cancer.
AB - Immunotherapy has clinical activity in certain virally associated cancers.
However, the tumor antigens targeted in successful treatments remain poorly
defined. We used a personalized immunogenomic approach to elucidate the global
landscape of antitumor T cell responses in complete regression of human
papillomavirus-associated metastatic cervical cancer after tumor-infiltrating
adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were
directed against mutated neoantigens or a cancer germline antigen, rather than
canonical viral antigens. T cells targeting viral tumor antigens did not display
preferential in vivo expansion. Both viral and nonviral tumor antigen-specific T
cells resided predominantly in the programmed cell death 1 (PD-1)-expressing T
cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor
T cell reactivities. These findings suggest a new paradigm of targeting nonviral
antigens in immunotherapy of virally associated cancers.
PMID- 28408607
TI - Crystal structure of the overlapping dinucleosome composed of hexasome and
octasome.
AB - Nucleosomes are dynamic entities that are repositioned along DNA by chromatin
remodeling processes. A nucleosome repositioned by the switch-sucrose
nonfermentable (SWI/SNF) remodeler collides with a neighbor and forms the
intermediate "overlapping dinucleosome." Here, we report the crystal structure of
the overlapping dinucleosome, in which two nucleosomes are associated, at 3.14
angstrom resolution. In the overlapping dinucleosome structure, the unusual
"hexasome" nucleosome, composed of the histone hexamer lacking one H2A-H2B dimer
from the conventional histone octamer, contacts the canonical "octasome"
nucleosome, and they intimately associate. Consequently, about 250 base pairs of
DNA are left-handedly wrapped in three turns, without a linker DNA segment
between the hexasome and octasome moieties. The overlapping dinucleosome
structure may provide important information to understand how nucleosome
repositioning occurs during the chromatin remodeling process.
PMID- 28408609
TI - Skiing for science.
PMID- 28408610
TI - Classic Spotlight, 1984 and 1985: Articles of Significant Interest Selected from
the Journal of Virology Archives by the Editors.
PMID- 28408611
TI - Correction for Doukas and Sarnow, "Escape from Transcriptional Shutoff during
Poliovirus Infection: NF-kappaB-Responsive Genes IkappaBa and A20".
PMID- 28408613
TI - Air pollution and the incidence of ischaemic and haemorrhagic stroke in the South
London Stroke Register: a case-cross-over analysis.
AB - BACKGROUND: Few European studies investigating associations between short-term
exposure to air pollution and incident stroke have considered stroke subtypes.
Using information from the South London Stroke Register for 2005-2012, we
investigated associations between daily concentrations of gaseous and particulate
air pollutants and incident stroke subtypes in an ethnically diverse area of
London, UK. METHODS: Modelled daily pollutant concentrations based on a
combination of measurements and dispersion modelling were linked at postcode
level to incident stroke events stratified by haemorrhagic and ischaemic
subtypes. The data were analysed using a time-stratified case-cross-over
approach. Conditional logistic regression models included natural cubic splines
for daily mean temperature and daily mean relative humidity, a binary term for
public holidays and a sine-cosine annual cycle. Of primary interest were same day
mean concentrations of particulate matter <2.5 and <10 um in diameter (PM2.5,
PM10), ozone (O3), nitrogen dioxide (NO2) and NO2+nitrogen oxide (NOX). RESULTS:
Our analysis was based on 1758 incident strokes (1311 were ischaemic and 256 were
haemorrhagic). We found no evidence of an association between all stroke or
ischaemic stroke and same day exposure to PM2.5, PM10, O3, NO2 or NOX. For
haemorrhagic stroke, we found a negative association with PM10 suggestive of a
14.6% (95% CI 0.7% to 26.5%) fall in risk per 10 ug/m3 increase in pollutant.
CONCLUSIONS: Using data from the South London Stroke Register, we found no
evidence of a positive association between outdoor air pollution and incident
stroke or its subtypes. These results, though in contrast to recent meta
analyses, are not inconsistent with the mixed findings of other UK studies.
PMID- 28408614
TI - Clinical Variant Classification: A Comparison of Public Databases and a
Commercial Testing Laboratory.
AB - BACKGROUND: There is a growing move to consult public databases following receipt
of a genetic test result from a clinical laboratory; however, the well-documented
limitations of these databases call into question how often clinicians will
encounter discordant variant classifications that may introduce uncertainty into
patient management. Here, we evaluate discordance in BRCA1 and BRCA2 variant
classifications between a single commercial testing laboratory and a public
database commonly consulted in clinical practice. MATERIALS AND METHODS: BRCA1
and BRCA2 variant classifications were obtained from ClinVar and compared with
the classifications from a reference laboratory. Full concordance and discordance
were determined for variants whose ClinVar entries were of the same pathogenicity
(pathogenic, benign, or uncertain). Variants with conflicting ClinVar
classifications were considered partially concordant if >=1 of the listed
classifications agreed with the reference laboratory classification. RESULTS:
Four thousand two hundred and fifty unique BRCA1 and BRCA2 variants were
available for analysis. Overall, 73.2% of classifications were fully concordant
and 12.3% were partially concordant. The remaining 14.5% of variants had
discordant classifications, most of which had a definitive classification
(pathogenic or benign) from the reference laboratory compared with an uncertain
classification in ClinVar (14.0%). CONCLUSION: Here, we show that discrepant
classifications between a public database and single reference laboratory
potentially account for 26.7% of variants in BRCA1 and BRCA2. The time and
expertise required of clinicians to research these discordant classifications
call into question the practicality of checking all test results against a
database and suggest that discordant classifications should be interpreted with
these limitations in mind. IMPLICATIONS FOR PRACTICE: With the increasing use of
clinical genetic testing for hereditary cancer risk, accurate variant
classification is vital to ensuring appropriate medical management. There is a
growing move to consult public databases following receipt of a genetic test
result from a clinical laboratory; however, we show that up to 26.7% of variants
in BRCA1 and BRCA2 have discordant classifications between ClinVar and a
reference laboratory. The findings presented in this paper serve as a note of
caution regarding the utility of database consultation.
PMID- 28408615
TI - Phase II Study of Bortezomib in Combination with Cyclophosphamide and Rituximab
for Relapsed or Refractory Mantle Cell Lymphoma.
AB - BACKGROUND: Relapsed or refractory mantle cell lymphoma (MCL) has a poor
prognosis. The best outcome is achieved in patients who have a partial or
complete response to salvage treatment and proceed to allogeneic stem cell
transplant. PATIENTS AND METHODS: Twenty-one patients were given a combination
regimen of bortezomib, cyclophosphamide, and rituximab at MD Anderson Cancer
Center as part of a single-arm, prospective, open-label phase II clinical trial.
The median age was 66 years, with a median number of prior treatments of three.
Sixty-seven percent had failed intensive chemoimmunotherapy and 43% were
intermediate/high risk according to the MCL international prognostic index score,
with a median Ki-67 proliferation index of 45% in those who were tested. RESULTS:
The rates of overall and complete response achieved were 74% and 42%,
respectively, with median progression-free and overall survivals of 9 months and
36.4 months, respectively. The regimen's toxicity profile was acceptable; only
25% of the cycles resulted in grade 3 or 4 neutropenia or thrombocytopenia, and
only 3% of cycles produced grade 3-4 fatigue. There were no episodes of grade 3-4
neuropathy. CONCLUSION: The combination of bortezomib with cyclophosphamide and
rituximab is an effective and well-tolerated regimen in patients with
relapsed/refractory MCL. Because of its low toxicity, future combinations of this
regimen with other promising drugs that have different mechanisms of action offer
a realistic possibility that may improve outcomes for patients who have MCL. The
Oncologist 2017;22:549-553 IMPLICATIONS FOR PRACTICE: The combination of
bortezomib with cyclophosphamide and rituximab represents an additional effective
novel salvage regimen for mantle cell lymphoma. This combination adds to the
growing list of treatment options available for patients with mantle cell
lymphoma.
PMID- 28408617
TI - Treatment Paradigms for Advanced Non-Small Cell Lung Cancer at Academic Medical
Centers: Involvement in Clinical Trial Endpoint Design.
AB - : Based on the positive results of various clinical trials, treatment options for
non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years.
While regulatory approvals of chemotherapeutic agents for NSCLC have largely been
based on improvements in overall survival, recent approvals of many targeted
agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based
on surrogate endpoints such as progression-free survival and objective response.
As such, selection of appropriate clinical endpoints for examining the efficacy
of investigational agents for NSCLC is of vital importance in clinical trial
design. This review provides an overview of clinical trial endpoints previously
utilized for approved agents for NSCLC and highlights the key efficacy results
for these trials. Trends for more recent approvals in NSCLC, including those for
the immunotherapeutic agents nivolumab and pembrolizumab, are also discussed. The
results of a correlative analysis of endpoints from 18 clinical trials that
supported approvals of investigational agents in clinical trials for NSCLC are
also presented. IMPLICATIONS FOR PRACTICE: While improving survival remains the
ultimate goal of oncology clinical trials, overall survival may not always be the
most feasible or appropriate endpoint to assess patient response. Recently,
several investigational agents, both targeted agents and immunotherapies, have
gained U.S. Food and Drug Administration approval in non-small cell lung cancer
based on alternate endpoints such as progression-free survival or response rate.
An understanding of the assessment of response and trial endpoint choice is
important for future oncology clinical trial design.
PMID- 28408616
TI - Association Study Confirmed Three Breast Cancer-Specific Molecular Subtype
Associated Susceptibility Loci in Chinese Han Women.
AB - BACKGROUND: Breast cancer is a heterogeneous and polygenic disease that can be
divided into different molecular subtypes based on histological and genomic
features. To date, numerous susceptibility loci of breast cancer have been
discovered by genome-wide association studies and may expand the genetic
features. However, few loci have been further studied according to molecular
subtypes. MATERIALS AND METHODS: We genotyped 23 recently discovered single
nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese
cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes)
and 3,036 healthy controls. RESULTS: Through a stratification analysis,
5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and
7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2
(rs35054928) was associated with Luminal B. CONCLUSION: In our study, breast
cancer-specific molecular subtype-associated susceptibility loci were confirmed
in Chinese Han women, which contributes to a better genetic understanding of
breast cancer in different molecular subtypes. IMPLICATIONS FOR PRACTICE: To
date, genome-wide association studies have identified more than 90 susceptibility
loci associated with breast cancer. However, few loci have been further studied
according to molecular subtype. The results of this study are that breast cancer
specific molecular subtype-associated susceptibility loci were confirmed in
Chinese Han women, which contributes to a better genetic understanding of breast
cancer in different molecular subtypes.
PMID- 28408618
TI - National Policies Fostering Hospice Care Increased Hospice Utilization and
Reduced the Invasiveness of End-of-Life Care for Cancer Patients.
AB - BACKGROUND: In 2011, two national policies aiming to foster hospice services for
terminal cancer patients took effect in Taiwan. The single-payer National Health
Insurance of Taiwan started to reimburse full hospice services. The national
hospital accreditation program, which graded all hospitals, incorporated hospice
utilization in its evaluation. We assessed the impact of these national policies.
METHODS: A cohort of 249,394 patients aged >=18 years who died of cancer between
2008 and 2013 were identified from the National Death Registry. We retrieved
utilization data of medical services and compared the health care utilization in
the final month of life before and after the implementation of the new policies.
RESULTS: After the policy changes, hospice utilization increased from 20.8% to
36.2%. In a multivariate analysis adjusting for patient demographics, cancer
features, and hospital characteristics, hospice utilization significantly
increased after 2011 (adjusted odds ratio [AOR] 2.35, p < .001), accompanied by a
decrease in intensive care unit (ICU) admissions, invasive mechanical ventilation
(IMV), and cardiopulmonary resuscitation (CPR; AORs 0.87, 0.75, and 0.80,
respectively; all p < .001). The patients who received hospice services were
significantly less likely to receive ICU admissions, IMV, and CPR (AORs 0.20,
0.12, and 0.10, respectively; all p < .001). Hospice utilization was associated
with an adjusted net savings of U.S. $696.90 (25.2%, p < .001) per patient in the
final month of life. CONCLUSION: The national policy changes fostering hospice
care significantly increased hospice utilization, decreased invasive end-of-life
care, and reduced the medical costs of terminal cancer patients. IMPLICATIONS FOR
PRACTICE: National policies fostering hospice care significantly increased
hospice utilization, decreased invasive end-of-life care, and reduced the medical
costs of terminal cancer patients.
PMID- 28408619
TI - Data Linkage to Improve Geriatric Oncology Research: A Feasibility Study.
AB - Older adults (aged 65 years and older) diagnosed with cancer account for most
cancer-related morbidity and mortality in the United States but are often
underrepresented on clinical trials. Recent attention from a variety of
professional, research, regulatory, and patient advocacy groups has centered on
data linkage and data sharing as a means to capture patient information and
outcomes outside of clinical trials to accelerate progress in the fight against
cancer. The development of a more robust observational research data
infrastructure would help to address gaps in the evidence base regarding optimal
approaches to treating cancer among the growing and complex population of older
adults. To demonstrate the feasibility of building such a resource, we linked
information from a sample of older adults with cancer in North Carolina using
three distinct, but complementary, data sources: (a) the Carolina Senior
Registry, (b) the North Carolina Central Cancer Registry, and (c) North Carolina
fee-for-service Medicare claims data. A description of the linkage process,
metrics, and characteristics of the final cohort is reported. This study
highlights the potential for data linkage to improve the characterization of
health status among older adults with cancer and the possibility to conduct
passive follow-up for outcomes of interest over time. Extensions of these linkage
efforts in partnership with other institutions will enhance our ability to
generate evidence that can inform the management of older adults with cancer.
PMID- 28408620
TI - Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical
Values.
AB - : Oncofertility is a unique, multidisciplinary field that serves to bridge the
gap between available fertility resources and the special reproductive needs of
cancer patients. Oncofertility is a growing field due to the increasing number of
survivors, development of new oncologic therapies, extension of duration of
therapies, and development and refinement of reproductive therapies. While the
technologies and demand for services expand, clinicians need to be appropriately
prepared for dealing with various clinical scenarios that may require ethical
deliberation. Three real cases are presented in which the patient wishes to
pursue reproductive assistance, but her decision is met with hesitance or
uncertainty by her care team. Discussion of these clinical scenarios highlights
ethical implications of oncofertility practice and serves to highlight the need
for the establishment of multidisciplinary care teams and guidelines to support
both clinicians and patients. IMPLICATIONS FOR PRACTICE: The growing field of
oncofertility is ripe for conflict between patient autonomy and medical values
due to the nature of cancer and associated threat on an individual's health and
survival, as well as the personal significance of childbearing. Cases are
presented and ethical implications are discussed to further explore the inherent
difficulties in oncofertility practice and guide clinicians in similar
situations. Developing guidelines and establishing multidisciplinary teams to
facilitate oncofertility discussions and care, as well as training of clinical
team members, may improve patient safety, well-being, and satisfaction within the
context of fertility decision making, care, and outcomes.
PMID- 28408621
TI - Endocrine Therapy Initiation and Medical Oncologist Utilization Among Women
Diagnosed with Ductal Carcinoma in Situ.
AB - BACKGROUND: Though randomized clinical trials have demonstrated a reduction in
second breast events with endocrine therapy among women with ductal carcinoma in
situ (DCIS), use of these therapies remains highly variable. The purpose of this
study was to evaluate patient and treatment-related factors associated with
endocrine therapy initiation and medical oncology specialty utilization after
DCIS. MATERIALS AND METHODS: We identified women with a DCIS diagnosis during
2006-2010 in the North Carolina Central Cancer Registry with linked public and
private insurance claims in the University of North Carolina Integrated Cancer
Information Surveillance System data resource. Multivariable generalized linear
regression models were used to estimate risk ratios (RR) and 95% confidence
intervals (CI) for endocrine therapy initiation in the year following DCIS
diagnosis. RESULTS: Among 2,090 women with a DCIS diagnosis, 37% initiated
endocrine therapy. Initiation was less common among women aged 75+ at diagnosis
(RR = 0.79; 95% CI: 0.64-0.97 vs. age 45-54) and women treated with breast
conserving surgery (BCS) who did not receive radiation (RR = 0.63; 95% CI: 0.50
0.78 vs. BCS plus radiation). Consultation with a medical oncologist was strongly
associated with endocrine therapy initiation (RR = 1.40; 95% CI: 1.23-1.61).
Women who saw a medical oncologist more often had private insurance, higher
census tract-level income, hormone receptor positive disease, and treatment with
BCS and radiation. CONCLUSION: Treatment strategies for DCIS remain
controversial. Our data suggest that endocrine therapy is more often used in
addition to standard therapies such as BCS plus radiation, rather than as an
alternative to radiation. The Oncologist 2017;22:535-541 IMPLICATIONS FOR
PRACTICE: Randomized trials have demonstrated a reduction in second breast cancer
events with use of endocrine therapy for ductal carcinoma in situ (DCIS).
However, notable variation exists in the uptake of these therapies among DCIS
patients. In this study, factors associated with endocrine therapy initiation in
the year following a DCIS diagnosis included consultation with a medical
oncologist and treatment with breast-conserving surgery with radiation. Our
findings help to explain the wide variation in endocrine therapy initiation and
suggest the need for clear guidelines in the treatment of DCIS.
PMID- 28408622
TI - A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell
Lymphoma.
AB - BACKGROUND: Decision-making models for elderly patients with diffuse large B-cell
lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP) are in great demand. PATIENTS AND METHODS:
The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the
West-Japan Hematology and Oncology Group (West-JHOG), collected and
retrospectively analyzed the clinical records of >=65-year-old patients with
DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that
can stratify adherence to R-CHOP. RESULTS: A total of 836 patients with a median
age of 74 years (range, 65-96 years) were analyzed. In the SoLT-J cohort (n =
555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity
Index score >=3 were independent adverse risk factors and were defined as the
Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score,
patients were categorized into "excellent" (0 points), "good" (1 point),
"moderate" (2 points), and "poor" (3 points) groups. This grouping effectively
discriminated the 3-year overall survival rates, mean relative total doses (or
relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R
CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death
rates. Additionally, the ACA index showed comparable results for these clinical
parameters when it was applied to the West-JHOG cohort (n = 281). CONCLUSION: The
ACA index has the ability to stratify the prognosis, tolerability to cytotoxic
drugs, and adherence to treatment of elderly patients with DLBCL treated with R
CHOP. The Oncologist 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little
is known regarding how to identify elderly patients with diffuse large B-cell
lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic
drugs should be reduced in some specific conditions. The Society of Lymphoma
Treatment in Japan developed a host-dependent prognostic model consisting of
higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson
Comorbidity Index score (>=3) for such elderly patients. This model can stratify
the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of
these patients and thus help clinicians in formulating personalized treatment
strategies for this growing patient population.
PMID- 28408625
TI - ETS (E26 transformation-specific) up-regulation of the transcriptional co
activator TAZ promotes cell migration and metastasis in prostate cancer.
AB - Prostate cancer is a very common malignant disease and a leading cause of death
for men in the Western world. Tumorigenesis and progression of prostate cancer
involves multiple signaling pathways, including the Hippo pathway. Yes-associated
protein (YAP) is the downstream transcriptional co-activator of the Hippo
pathway, is overexpressed in prostate cancer, and plays a vital role in the
tumorigenesis and progression of prostate cancer. However, the role of the YAP
paralog and another downstream effector of the Hippo pathway, transcriptional co
activator with PDZ-binding motif (TAZ), in prostate cancer has not been fully
elucidated. Here, we show that TAZ is a basal cell marker for the prostate
epithelium. We found that overexpression of TAZ promotes the epithelial
mesenchymal transition (EMT), cell migration, and anchorage-independent growth in
the RWPE1 prostate epithelial cells. Of note, knock down of TAZ in the DU145
prostate cancer cells inhibited cell migration and metastasis. We also found that
SH3 domain binding protein 1 (SH3BP1), a RhoGAP protein that drives cell
motility, is a direct target gene of TAZ in the prostate cancer cells, mediating
TAZ function in enhancing cell migration. Moreover, the prostate cancer-related
oncogenic E26 transformation-specific (ETS) transcription factors, ETV1, ETV4,
and ETV5, were required for TAZ gene transcription in PC3 prostate cancer cells.
MAPK inhibitor U0126 treatment decreased TAZ expression in RWPE1 cells, and ETV4
overexpression rescued TAZ expression in RWPE1 cells with U0126 treatment. Our
results show a regulatory mechanism of TAZ transcription and suggest a
significant role for TAZ in the progression of prostate cancer.
PMID- 28408626
TI - Differences in Activation and Deactivation in Children with Sickle Cell Disease
Compared with Demographically Matched Controls.
AB - BACKGROUND AND PURPOSE: Declines in both functional activation and functional
connectivity have been reported in patients with sickle cell disease. In this
study, we derived the functional and default mode responses to a word stem
paradigm in age-, ethnicity-, and background-matched subjects with sickle cell
disease and control groups, with the aim of testing whether both networks were
similarly attenuated and whether the changes were related to physiologic
parameters that characterize sickle cell disease. MATERIALS AND METHODS: Both the
functional and default mode responses were obtained from age- and background
matched controls and the sickle cell population by using a visually presented
word stem paradigm on a 3T scanner. RESULTS: We observed an attenuated response
to both activation and deactivation in the sickle cell disease group. There were
no significant differences in the activation response between the 2 groups for
the contrast control > sickle cell disease; however, significant differences were
observed in the medial parietal cortex, the auditory cortex, and the angular
gyrus for the default mode. For the sickle cell group, a significant correlation
between the activation z scores and the physiologic parameters was observed; for
the deactivation, the results were not significant but the trend was similar.
CONCLUSIONS: The results indicate that the physiologic parameters modulate the
activation in the expected fashion, but that the effect was weaker for
deactivation. Given that significant differences between the 2 groups were only
seen for deactivation, additional factors must modulate the deactivation in
sickle cell disease.
PMID- 28408623
TI - Protein kinase D1 (PKD1) phosphorylation on Ser203 by type I p21-activated kinase
(PAK) regulates PKD1 localization.
AB - Although PKC-mediated phosphorylation of protein kinase D1 (PKD1) has been
extensively characterized, little is known about PKD1 regulation by other
upstream kinases. Here we report that stimulation of epithelial or fibroblastic
cells with G protein-coupled receptor agonists, including angiotensin II or
bombesin, induced rapid and persistent PKD1 phosphorylation at Ser203, a highly
conserved residue located within the PKD1 N-terminal domain. Exposure to PKD or
PKC family inhibitors did not prevent PKD1 phosphorylation at Ser203, indicating
that it is not mediated by autophosphorylation. In contrast, several lines of
evidence indicated that the phosphorylation of PKD1 at Ser203 is mediated by
kinases of the class I PAK subfamily, specifically 1) exposing cells to four
structurally unrelated PAK inhibitors (PF-3758309, FRAX486, FRAX597, and IPA-3)
that act via different mechanisms abrogated PKD1 phosphorylation at Ser203, 2)
siRNA-mediated knockdown of PAK1 and PAK2 in IEC-18 and Swiss 3T3 cells blunted
PKD1 phosphorylation at Ser203, 3) phosphorylation of Ser203 markedly increased
in vitro when recombinant PKD1 was incubated with either PAK1 or PAK2 in the
presence of ATP. PAK inhibitors did not interfere with G protein-coupled receptor
activation-induced rapid translocation of PKD1 to the plasma membrane but
strikingly prevented the dissociation of PKD1 from the plasma membrane and
blunted the phosphorylation of nuclear targets, including class IIa histone
deacetylases. We conclude that PAK-mediated phosphorylation of PKD1 at Ser203
triggers its membrane dissociation and subsequent entry into the nucleus, thereby
regulating the phosphorylation of PKD1 nuclear targets, including class IIa
histone deacetylases.
PMID- 28408627
TI - Minor Stroke Syndromes in Large-Vessel Occlusions: Mechanical Thrombectomy or
Thrombolysis Only?
AB - While mechanical thrombectomy for large-vessel occlusions is now an evidence
based treatment, its efficacy and safety in minor stroke syndromes (NIHSS <= 5)
is not proved. We identified, in our prospective data base, 378 patients with
minor strokes in the anterior circulation; 54 (14.2%) of these had proved large
vessel occlusions. Eight of 54 (14.8%) were immediately treated with mechanical
thrombectomy, 6/54 (11.1%) after early neurologic deterioration, and the rest
were treated with standard thrombolysis only. Rates of successful recanalization
were similar between the 2 mechanical thrombectomy groups (75% versus 100%).
Rates of excellent outcome (modified Rankin Scale 0-1) were higher in patients
with immediate thrombectomy (75%) compared with patients with delayed
thrombectomy (33.3%) and thrombolysis only (55%). No symptomatic intracranial
hemorrhage occurred in either group. These descriptive data are encouraging, and
further analysis of large registries or even randomized controlled trials in this
patient subgroup should be performed.
PMID- 28408624
TI - Activated protein C inhibits neutrophil extracellular trap formation in vitro and
activation in vivo.
AB - Activated protein C (APC) is a multifunctional serine protease with
anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to
the cytoprotective effects of APC on endothelial cells, podocytes, and neurons,
APC cleaves and detoxifies extracellular histones, a major component of
neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also
can lead to thrombosis; the pathways that negatively regulate NETosis are largely
unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis
via receptor-mediated cell signaling mechanisms. Here, by quantifying
extracellular DNA or myeloperoxidase, we demonstrate that APC binds human
leukocytes and prevents activated platelet supernatant or phorbol 12-myristate 13
acetate (PMA) from inducing NETosis. Of note, APC proteolytic activity was
required for inhibiting NETosis. Moreover, antibodies against the neutrophil
receptors endothelial protein C receptor (EPCR), protease-activated receptor 3
(PAR3), and macrophage-1 antigen (Mac-1) blocked APC inhibition of NETosis.
Select mutations in the Gla and protease domains of recombinant APC caused a loss
of NETosis. Interestingly, pretreatment of neutrophils with APC prior to
induction of NETosis inhibited platelet adhesion to NETs. Lastly, in a nonhuman
primate model of Escherichia coli-induced sepsis, pretreatment of animals with
APC abrogated release of myeloperoxidase from neutrophils, a marker of neutrophil
activation. These findings suggest that the anti-inflammatory function of APC at
therapeutic concentrations may include the inhibition of NETosis in an EPCR-,
PAR3-, and Mac-1-dependent manner, providing additional mechanistic insight into
the diverse functions of neutrophils and APC in disease states including sepsis.
PMID- 28408628
TI - Dentate Update: Imaging Features of Entities That Affect the Dentate Nucleus.
AB - The dentate nucleus is a cerebellar structure involved in voluntary motor
function and cognition. There are relatively few entities that affect the
dentate, and the clinical features of these conditions are often complex and
nonspecific. Because these entities are rarely encountered, the formulation of a
differential diagnosis can be difficult. Many of the conditions are reversible or
treatable with early intervention. Therefore, it is important to recognize
classic clinical presentations and their associated characteristic imaging
findings. We provide a summary of entities that affect the dentate nucleus and a
diagnostic workflow for approaching dentate nucleus imaging abnormalities.
PMID- 28408629
TI - Pretreatment ADC Values Predict Response to Radiosurgery in Vestibular
Schwannomas.
AB - BACKGROUND AND PURPOSE: The response rate of vestibular schwannomas to radiation
therapy is variable, and there are surgical options available in the event of
treatment failure. The aim of this study was to determine whether pre- and
posttreatment ADC values can predict the tumor response to radiation therapy.
MATERIALS AND METHODS: From a data base of 162 patients with vestibular
schwannomas who underwent radiation therapy with gamma knife, CyberKnife, or
fractionated stereotactic radiation therapy as the first-line therapy between
January 2003 and December 2013, we found 20 patients who had pretreatment ADC
values. There were 108 patients (including these 20) had serial MR images that
included DWI allowing calculated ADC values from 2-132 months after radiation
therapy. Two reviewers measured the mean, minimum, and maximum ADC values from
elliptical ROIs that included tumor tissue only. Treatment responders were
defined as those with a tumor total volume shrinkage of 20% or more after
radiation therapy. RESULTS: The pretreatment mean minimum ADC for nonresponders
was 986.7 * 10-6 mm2/s (range, 844-1230 * 10-6 mm2/s) and it was 669.2 * 10-6
mm2/s (range, 345-883 * 10-6 mm2/s) for responders. This difference was
statistically significant (P < .001). Using a minimum ADC value of 800 * 10-6
mm2/s led to the correct classification of 18/20 patients based on pretreatment
ADC values. The intraclass correlation between reviewers was 0.61. No
posttreatment ADC values predicted response. CONCLUSIONS: Pretreatment ADC values
of vestibular schwannomas are lower in responders than nonresponders. Using a
minimum ADC value of 800 * 10-6 mm2/s correctly classified 90% of cases.
PMID- 28408630
TI - Current and Emerging Therapies in Multiple Sclerosis: Implications for the
Radiologist, Part 1-Mechanisms, Efficacy, and Safety.
AB - Imaging for the diagnosis and follow-up of patients with suspected or confirmed
multiple sclerosis is a common scenario for many general radiologists and
subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved
with multiple new agents now being used in routine clinical practice. To provide
an informed opinion in discussions concerning newer MS agents, radiologists must
have a working understanding of the strengths and limitations of the various
novel therapies. The role of imaging in MS has advanced beyond monitoring and
surveillance of disease activity to include treatment complications. An
understanding of the new generation of MS drugs in conjunction with the key role
that MR imaging plays in the detection of disease progression, opportunistic
infections, and drug-related adverse events is of vital importance to the
radiologist and clinical physician alike. Radiologists are in a unique position
to detect many of the described complications well in advance of clinical
symptoms. Part 1 of this review outlines recent developments in the treatment of
MS and discusses the published clinical data on the efficacy and safety of the
currently approved and emerging therapies in this condition as they apply to the
radiologist. Part 2 will cover pharmacovigilance and the role the
neuroradiologist plays in monitoring patients for signs of opportunistic
infection and/or disease progression.
PMID- 28408631
TI - Asymmetric Meckel Cave Enlargement: A Potential Marker of PHACES Syndrome.
AB - BACKGROUND AND PURPOSE: PHACES syndrome is a complex of morphologic abnormalities
of unknown cause and includes posterior fossa abnormalities; head and neck
infantile hemangiomas; arterial, cardiac, and eye anomalies; and sternal or
abdominal wall defects. Accurate identification of the syndrome is important for
optimal treatment. The purpose of this study was to investigate the incidence of
asymmetric Meckel cave enlargement, a potential novel imaging marker, in a
population of patients referred for evaluation of possible PHACES syndrome.
MATERIALS AND METHODS: Eighty-five patients referred for neuroimaging evaluation
of possible PHACES syndrome were identified and stratified on the basis of their
ultimate clinical PHACES diagnosis categorization into PHACES, possible PHACES,
or not PHACES. MR imaging studies were subsequently reviewed for the presence or
absence of unilateral Meckel cave enlargement, with the reviewer blinded to the
ultimate PHACES syndrome categorization. RESULTS: Twenty-five of 85 patients
(29%) were ultimately categorized as having PHACES or possible PHACES according
to consensus guidelines. Asymmetric Meckel cave enlargement was present in 76%
(19/25) of these patients and in 82% (19/23) of only those patients with definite
PHACES. This finding was present in none of the 60 patients determined not to
have PHACES syndrome. In 7/19 patients (37%) with this finding, subtle MR imaging
abnormalities consistent with PHACES were missed on the initial MR imaging
interpretation. CONCLUSIONS: Asymmetric Meckel cave enlargement was a common
feature of patients with PHACES in our cohort and may serve as a novel imaging
marker. Increased awareness of this imaging feature has the potential to increase
the diagnostic accuracy of PHACES.
PMID- 28408632
TI - 4D DSA for Dynamic Visualization of Cerebral Vasculature: A Single-Center
Experience in 26 Cases.
AB - BACKGROUND AND PURPOSE: 4D DSA allows acquisition of time-resolved 3D
reconstructions of cerebral vessels by using C-arm conebeam CT systems. The aim
of our study was to evaluate this new method by qualitative and quantitative
means. MATERIALS AND METHODS: 2D and 4D DSA datasets were acquired in patients
presenting with AVMs, dural arteriovenous fistulas, and cerebral aneurysms. 4D
DSA was compared with 2D DSA in a consensus reading of qualitative and
quantitative parameters of AVMs (eg, location, feeder, associated aneurysms,
nidus size, drainage, Martin-Spetzler Score), dural arteriovenous fistulas (eg,
fistulous point, main feeder, diameter of the main feeder, drainage), and
cerebral aneurysms (location, neck configuration, aneurysmal size).
Identifiability of perforators and diameters of the injection vessel (ICA,
vertebral artery) were analyzed in 2D and 4D DSA. Correlation coefficients and a
paired t test were calculated for quantitative parameters. The effective patient
dose of the 4D DSA protocol was evaluated with an anthropomorphic phantom.
RESULTS: In 26 patients, datasets were acquired successfully (AVM = 10, cerebral
aneurysm = 10, dural arteriovenous fistula = 6). Qualitative and quantitative
evaluations of 4D DSA in AVMs (nidus size: r = 0.99, P = .001), dural
arteriovenous fistulas (diameter of the main feeder: r = 0.954, P = .03), and
cerebral aneurysms (aneurysmal size: r = 1, P = .001) revealed nearly complete
accordance with 2D DSA. Perforators were comparably visualized with 4D DSA.
Measurement of the diameter of the injection vessel in 4D DSA was equivalent to
that in 2D DSA (P = .039). The effective patient dose of 4D DSA was 1.2 mSv.
CONCLUSIONS: 4D DSA is feasible for imaging of AVMs, dural arteriovenous
fistulas, and cerebral aneurysms. 4D DSA offers reliable visualization of the
cerebral vasculature and may improve the understanding and treatment of AVMs and
dural arteriovenous fistulas. The number of 2D DSA acquisitions required for an
examination may be reduced through 4D DSA.
PMID- 28408633
TI - Heterogeneity of Cortical Lesion Susceptibility Mapping in Multiple Sclerosis.
AB - BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been used to
characterize iron and myelin content in the deep gray matter of patients with
multiple sclerosis. Our aim was to characterize the susceptibility mapping of
cortical lesions in patients with MS and compare it with neuropathologic
observations. MATERIALS AND METHODS: The pattern of microglial activation was
studied in postmortem brain tissues from 16 patients with secondary-progressive
MS and 5 age-matched controls. Thirty-six patients with MS underwent 3T MR
imaging, including 3D double inversion recovery and 3D-echo-planar SWI. RESULTS:
Neuropathologic analysis revealed the presence of an intense band of microglia
activation close to the pial membrane in subpial cortical lesions or to the WM
border of leukocortical cortical lesions. The quantitative susceptibility mapping
analysis revealed 131 cortical lesions classified as hyperintense; 33, as
isointense; and 84, as hypointense. Quantitative susceptibility mapping
hyperintensity edge found in the proximity of the pial surface or at the white
matter/gray matter interface in some of the quantitative susceptibility mapping
hyperintense cortical lesions accurately mirrors the microglia activation
observed in the neuropathology analysis. CONCLUSIONS: Cortical lesion
susceptibility maps are highly heterogeneous, even at individual levels.
Quantitative susceptibility mapping hyperintensity edge found in proximity to the
pial surface might be due to the subpial gradient of microglial activation.
PMID- 28408634
TI - Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with
increased salt retention and decreased renal nitric oxide.
AB - Previously, we reported that 20% fructose diet causes salt-sensitive
hypertension. In this study, we hypothesized that a high salt diet supplemented
with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by
increasing salt retention through decreasing renal nitric oxide. Rats in
metabolic cages consumed normal rat chow for 5 days (baseline), then either: (1)
normal salt for 2 weeks, (2) 20% fructose in drinking water for 2 weeks, (3) 20%
fructose for 1 week, then fructose + high salt (4% NaCl) for 1 week, (4) normal
chow for 1 week, then high salt for 1 week, (5) 20% glucose for 1 week, then
glucose + high salt for 1 week. Blood pressure, sodium excretion, and cumulative
sodium balance were measured. Systolic blood pressure was unchanged by 20%
fructose or high salt diet. 20% fructose + high salt increased systolic blood
pressure from 125 +/- 1 to 140 +/- 2 mmHg (P < 0.001). Cumulative sodium balance
was greater in rats consuming fructose + high salt than either high salt, or
glucose + high salt (114.2 +/- 4.4 vs. 103.6 +/- 2.2 and 98.6 +/- 5.6 mEq/Day19;
P < 0.05). Sodium excretion was lower in fructose + high salt group compared to
high salt only: 5.33 +/- 0.21 versus 7.67 +/- 0.31 mmol/24 h; P < 0.001). Nitric
oxide excretion was 2935 +/- 256 MUmol/24 h in high salt-fed rats, but reduced by
40% in the 20% fructose + high salt group (2139 +/- 178 MUmol /24 hrs P < 0.01).
Our results suggest that fructose predisposes rats to salt-sensitivity and,
combined with a high salt diet, leads to sodium retention, increased blood
pressure, and impaired renal nitric oxide availability.
PMID- 28408635
TI - Cardiac autonomic control and complexity during sleep are preserved after chronic
sleep restriction in healthy subjects.
AB - Acute sleep deprivation (SD) alters cardiovascular autonomic control (CAC) and is
associated with an increased risk of cardiovascular disorders. However, the
effects of partial SD on CAC are unclear. Thus, we aimed to investigate the
effects of partial SD on CAC during sleep. We randomized seventeen healthy
subjects to a restriction group (RES, n = 8, subjects slept two-thirds of normal
sleep time based on individual habitual sleep duration for 8 days and 8 nights)
or a Control group (CON, n = 9, subjects were allowed to sleep their usual sleep
time). Attended polysomnographic (PSG) studies were performed every night; a
subset of them was selected for the analysis at baseline (day 3-D3), the first
night after sleep restriction (day 5-D5), at the end of sleep restriction period
(day 11-D11), and at the end of recovery phase (day 14-D14). We extracted
electrocardiogram (ECG) and respiration from the PSG and divided into wakefulness
(W), nonrapid eye movements (REM) sleep (N2 and N3) and REM sleep. CAC was
evaluated by means of linear spectral analysis, nonlinear symbolic analysis and
complexity indexes. In both RES and CON groups, sympathetic modulation decreased
and parasympathetic modulation increased during N2 and N3 compared to W and REM
at D3, D5, D11, D14. Complexity analysis revealed a reduction in complexity
during REM compared to NREM sleep in both DEP and CON After 8 days of moderate
SD, cardiac autonomic dynamics, characterized by decreased sympathetic, and
increased parasympathetic modulation, and higher cardiac complexity during NREM
sleep, compared to W and REM, are preserved.
PMID- 28408636
TI - Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response
element in the sgk1 5' regulatory region.
AB - We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3)
encoding an NH2-terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is
expressed in the distal convoluted tubule, connecting tubule and collecting duct
and can stimulate epithelial Na+ transport (Am J Physiol Renal Physiol 303: F1527
F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and
glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting
duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers
that increase endogenous aldosterone secretion including dietary Na+ deprivation
and K+ loading increases distal nephron Sgk1_v3 expression in vivo. Although
Sgk1_v3 has a different 5' proximal regulatory region from Sgk1, the
transcription start sites are less than 1000 bp apart. We cloned the 5'
regulatory region for Sgk1 and Sgk_v3 upstream of a luciferase gene and by
deletion and reporter gene analysis we localized the corticosteroid regulatory
region for Sgk1_v3 to a glucocorticoid response element (GRE) that had previously
been identified for Sgk1 (Am J Physiol Endo Metab 283: E971-E979, 2002). We
tested this element with MR in an MR-null cell line and demonstrate that
aldosterone stimulates Sgk1 and Sgk1_v3 via this GRE We conclude that
corticosteroids stimulate Sgk1 and Sgk1_v3 expression in epithelial cells via
activation of a common conserved GRE in the 5' flanking region of Sgk1.
PMID- 28408637
TI - A new player in interstitial cystitis/bladder pain syndrome: platelet-activating
factor - PAF and its connection to smoking.
PMID- 28408638
TI - Blindfolding during wakefulness causes decrease in sleep slow wave activity.
AB - Slow wave activity (SWA, 0.5-4 Hz) represents the predominant EEG oscillatory
activity during slow wave sleep (SWS). Its amplitude is considered in part a
reflection of synaptic potentiation in cortical networks due to encoding of
information during prior waking, with higher amplitude indicating stronger
potentiation. Previous studies showed that increasing and diminishing specific
motor behaviors produced corresponding changes in SWA in the respective motor
cortical areas during subsequent SWS Here, we tested whether this relationship
can be generalized to the visual system, that is, whether diminishing encoding of
visual information likewise leads to a localized decrease in SWA over the visual
cortex. Experiments were performed in healthy men whose eyes on two different
days were or were not covered for 10.5 h before bedtime. The subject's EEG was
recorded during sleep and, after sleep, visual evoked potentials (VEPs) were
recorded. SWA during nonrapid eye movement sleep (NonREM sleep) was lower after
blindfolding than after eyes open (P < 0.01). The decrease in SWA that was most
consistent during the first 20 min of NonREM sleep, did not remain restricted to
visual cortex regions, with changes over frontal and parietal cortical regions
being even more pronounced. In the morning after sleep, the N75-P100 peak-to-peak
amplitude of the VEP was significantly diminished in the blindfolded condition.
Our findings confirm a link between reduced wake encoding and diminished SWA
during ensuing NonREM sleep, although this link appears not to be restricted to
sensory cortical areas.
PMID- 28408639
TI - Interaction between neuronal calcium sensor protein 1 and lithium in
pedunculopontine neurons.
AB - Bipolar disorder is characterized by sleep dysregulation, suggesting a role for
the reticular activating system (RAS). Postmortem studies showed increased
expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some
bipolar disorder patients, and reduced or aberrant gamma band activity is present
in the same disorder. Lithium (Li+) has been shown to effectively treat the mood
disturbances in bipolar disorder patients. We previously showed that NCS-1 at low
levels increased, and at high levels decreased, gamma oscillations in RAS
pedunculopontine neurons (PPN), and that Li+ decreased these oscillations. We
previously described the effects of each agent on oscillations, G-protein
mechanisms, and Ca2+ currents. However, we designed the present experiments to
determine the nature of the interaction of NCS-1 and Li+ at physiological
concentrations that would have an effect within minutes of application. As
expected, Li+ decreased gamma oscillation amplitude, while NCS-1 increased the
amplitude of gamma oscillations. We identified NCS-1 at 2 MUmol/L as a
concentration that increased gamma oscillations within 5-10 min, and Li+ at 10
MUmol/L as a concentration that decreased gamma oscillations within 5 min. The
combined application of NCS-1 and Li+ at these concentrations showed that Li+
reduced the effects of NCS-1 on oscillation amplitude within 5-10 min. These
results demonstrate that at physiological levels, Li+ acts to reduce the effects
of NCS-1 so that, given over expression of NCS-1, Li+ would have salutary
effects.
PMID- 28408640
TI - Long-term, but not short-term high-fat diet induces fiber composition changes and
impaired contractile force in mouse fast-twitch skeletal muscle.
AB - In this study, we investigated the effects of a short-term and long-term high-fat
diet (HFD) on morphological and functional features of fast-twitch skeletal
muscle. Male C57BL/6J mice were fed a HFD (60% fat) for 4 weeks (4-week HFD) or
12 weeks (12-week HFD). Subsequently, the fast-twitch extensor digitorum longus
muscle was isolated, and the composition of muscle fiber type, expression levels
of proteins involved in muscle contraction, and force production on electrical
stimulation were analyzed. The 12-week HFD, but not the 4-week HFD, resulted in a
decreased muscle tetanic force on 100 Hz stimulation compared with control (5.1
+/- 1.4 N/g in the 12-week HFD vs. 7.5 +/- 1.7 N/g in the control group; P <
0.05), whereas muscle weight and cross-sectional area were not altered after both
HFD protocols. Morphological analysis indicated that the percentage of type IIx
myosin heavy chain fibers, mitochondrial oxidative enzyme activity, and
intramyocellular lipid levels increased in the 12-week HFD group, but not in the
4-week HFD group, compared with controls (P < 0.05). No changes in the expression
levels of calcium handling-related proteins and myofibrillar proteins (myosin
heavy chain and actin) were detected in the HFD models, whereas fast-troponin T
protein expression was decreased in the 12-week HFD group, but not in the 4-week
HFD group (P < 0.05). These findings indicate that a long-term HFD, but not a
short-term HFD, impairs contractile force in fast-twitch muscle fibers. Given
that skeletal muscle strength largely depends on muscle fiber type, the impaired
muscle contractile force by a HFD might result from morphological changes of
fiber type composition.
PMID- 28408641
TI - Gastroparesis and lipid metabolism-associated dysbiosis in Wistar-Kyoto rats.
AB - Altered gastric accommodation and intestinal morphology suggest impaired
gastrointestinal (GI) transit may occur in the Wistar-Kyoto (WKY) rat strain, as
common in stress-associated functional GI disorders. Because changes in GI
transit can alter microbiota composition, we investigated whether these are
altered in WKY rats compared with the resilient Sprague-Dawley (SD) rats under
basal conditions and characterized plasma lipid and metabolite differences. Bead
transit was tracked by X-ray imaging to monitor gastric emptying (4 h), small
intestine (SI) transit (9 h), and large intestine transit (12 h). Plasma extracts
were analyzed by lipid and hydrophilic interaction liquid chromatography (HILIC)
and liquid chromatography-mass spectrometry (LC-MS). Cecal microbial composition
was determined by Illumina MiSeq 16S rRNA amplicon sequencing and analysis using
the QIIME pipeline. Stomach retention of beads was 77% for WKY compared with 35%
for SD rats. GI transit was decreased by 34% (9 h) and 21% (12 h) in WKY compared
with SD rats. Excluding stomach retention, transiting beads moved 29% further
along the SI over 4-9 h for WKY compared with SD rats. Cecal Ruminococcus,
Roseburia, and unclassified Lachnospiraceae genera were less abundant in WKY
rats, whereas the minor taxa Dorea, Turicibacter, and Lactobacillus were higher.
Diglycerides, triglycerides, phosphatidyl-ethanolamines, and phosphatidylserine
were lower in WKY rats, whereas cholesterol esters and taurocholic acids were
higher. The unexpected WKY rat phenotype of delayed gastric emptying, yet rapid
SI transit, was associated with altered lipid and metabolite profiles. The
delayed gastric emptying of the WKY phenotype suggests this rat strain may be
useful as a model for gastroparesis.NEW & NOTEWORTHY This study reveals that the
stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis
and rapid small intestine transit, together with metabolic changes consistent
with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats.
This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model
for gastroparesis.
PMID- 28408642
TI - Elevated intrabolus pressure identifies obstructive processes when integrated
relaxation pressure is normal on esophageal high-resolution manometry.
AB - Elevated integrated relaxation pressure (IRP) on esophageal high-resolution
manometry (HRM) identifies obstructive processes at the esophagogastric junction
(EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify
structural EGJ processes when IRP is normal. In this observational cohort study,
adult patients with dysphagia and undergoing HRM were evaluated for endoscopic
evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the
setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI),
distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared
among 74 patients with structural EGJ findings (62.8 +/- 1.6 yr, 67.6% women), 27
patients with normal EGD (52.9 +/- 3.2 yr, 70.3% women), and 21 healthy controls
(27.6 +/- 0.6 yr, 52.4% women). Findings were validated in 85 consecutive
symptomatic patients to address clinical utility. In the primary cohort, mean IBP
(18.4 +/- 0.9 mmHg) was higher with structural EGJ findings compared with
dysphagia with normal EGD (13.5 +/- 1.1 mmHg, P = 0.002) and healthy controls
(10.9 +/- 0.9 mmHg, P < 0.001). However, mean IRP, DCI, DL, and EGJ-CI were
similar across groups (P > 0.05 for each comparison). During multiple rapid
swallows, IBP remained higher in the structural findings group compared with
controls (P = 0.02). Similar analysis of the prospective validation cohort
confirmed IBP elevation in structural EGJ processes, but correlation with
dysphagia could not be demonstrated. We conclude that elevated IBP predicts the
presence of structural EGJ processes even when IRP is normal, but correlation
with dysphagia is suboptimal.NEW & NOTEWORTHY Integrated relaxation pressure
(IRP) above the upper limit of normal defines esophageal outflow obstruction
using high-resolution manometry. In patients with normal IRP, elevated intrabolus
pressure (IBP) can be a surrogate marker for a structural restrictive or
obstructive process at the esophagogastric junction (EGJ). This has the potential
to augment the clinical value of esophageal HRM by raising suspicion for a
structural EGJ process when IBP is elevated.
PMID- 28408643
TI - Gastrin induces parathyroid hormone-like hormone expression in gastric parietal
cells.
AB - Parietal cells play a fundamental role in stomach maintenance, not only by
creating a pathogen-free environment through the production of gastric acid, but
also by secreting growth factors important for homeostasis of the gastric
epithelium. The gastrointestinal hormone gastrin is known to be a central
regulator of both parietal cell function and gastric epithelial cell
proliferation and differentiation. Our previous gene expression profiling studies
of mouse stomach identified parathyroid hormone-like hormone (PTHLH) as a
potential gastrin-regulated gastric growth factor. Although PTHLH is commonly
overexpressed in gastric tumors, its normal expression, function, and regulation
in the stomach are poorly understood. In this study we used pharmacologic and
genetic mouse models as well as human gastric cancer cell lines to determine the
cellular localization and regulation of this growth factor by the hormone
gastrin. Analysis of PthlhLacZ/+ knock-in reporter mice localized Pthlh
expression to parietal cells in the gastric corpus. Regulation by gastrin was
demonstrated by increased Pthlh mRNA abundance after acute gastrin treatment in
wild-type mice and reduced expression in gastrin-deficient mice. PTHLH
transcripts were also observed in normal human stomach as well as in human
gastric cancer cell lines. Gastrin treatment of AGS-E gastric cancer cells
induced a rapid and robust increase in numerous PTHLH mRNA isoforms. This
induction was largely due to increased transcriptional initiation, although
analysis of mRNA half-life showed that gastrin treatment also extended the half
life of PTHLH mRNA, suggesting that gastrin regulates expression by both
transcriptional and posttranscriptional mechanisms.NEW & NOTEWORTHY We show that
the growth factor parathyroid hormone-like hormone (PTHLH) is expressed in acid
secreting parietal cells of the mouse stomach. We define the specific PTHLH mRNA
isoforms expressed in human stomach and in human gastric cancer cell lines and
show that gastrin induces PTHLH expression via transcription activation and mRNA
stabilization. Our findings suggest that PTHLH is a gastrin-regulated growth
factor that might contribute to gastric epithelial cell homeostasis.
PMID- 28408645
TI - HIV videos on YouTube: helpful or harmful?
PMID- 28408644
TI - Human-derived gut microbiota modulates colonic secretion in mice by regulating 5
HT3 receptor expression via acetate production.
AB - Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a
paracrine messenger in the gastrointestinal tract, regulates intestinal secretion
by its action primarily on 5-HT3 and 5-HT4 receptors. Recent studies highlight
the role of gut microbiota in 5-HT biosynthesis. In this study, we determine
whether human-derived gut microbiota affects host secretory response to 5-HT and
5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation
from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized
with human gut microbiota) mice. 5-HT evoked a significantly greater increase in
short-circuit current (DeltaIsc) in GF compared with HM mice. Additionally, 5-HT3
receptor mRNA and protein expression was significantly higher in GF compared with
HM mice. Ondansetron, a 5-HT3 receptor antagonist, inhibited 5-HT-evoked DeltaIsc
in GF mice but not in HM mice. Furthermore, a 5-HT3 receptor-selective agonist, 2
methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher DeltaIsc
in GF compared with HM mice. Immunohistochemistry in 5-HT3A-green fluorescent
protein mice localized 5-HT3 receptor expression to enterochromaffin cells in
addition to nerve fibers. The significant difference in 5-HT-evoked DeltaIsc
between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was
lost after ondansetron application in the presence of TTX. Application of acetate
(10 mM) significantly lowered 5-HT3 receptor mRNA in GF mouse colonoids. We
conclude that host secretory response to 5-HT may be modulated by gut microbiota
regulation of 5-HT3 receptor expression via acetate production. Epithelial 5-HT3
receptor may function as a mediator of gut microbiota-driven change in intestinal
secretion.NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)
evoked intestinal secretion in a 5-HT3 receptor-dependent mechanism and gut
microbiota metabolite acetate alters 5-HT3 receptor expression in colonoids.View
this article's corresponding video summary at
https://www.youtube.com/watch?v=aOMYJMuLTcw&feature=youtu.be.
PMID- 28408646
TI - Response to: A double-edged sword: does highly active antiretroviral therapy
contribute to syphilis incidence by impairing immunity to Treponema pallidum?
PMID- 28408647
TI - Composition and Function of Mammalian SWI/SNF Chromatin Remodeling Complexes in
Human Disease.
AB - Mammalian SWI/SNF (BAF) chromatin remodeling complexes play critical roles in
maintaining chromatin architecture and gene expression. Genomic sequencing
efforts over the past several years have unveiled a major role for these
complexes in the development of human cancer as well as neurologic disease,
prompting the need to interrogate underlying mechanisms and to develop new
methods to comprehensively understand mSWI/SNF complex function. Here we discuss
the emerging insights from genetic, biochemical, and functional genomic studies
in the field and suggest approaches toward further basic investigations, as well
as therapeutic targeting of chromatin remodeling machinery.
PMID- 28408650
TI - Challenges and Pitfalls of Entrainment Mapping of Ventricular Tachycardia: Ten
Illustrative Concepts.
PMID- 28408649
TI - External Arrhythmia Ablation Using Photon Beams: Ablation of the Atrioventricular
Junction in an Intact Animal Model.
AB - BACKGROUND: This study sought to investigate external photon beam radiation for
catheter-free ablation of the atrioventricular junction in intact pigs. METHODS
AND RESULTS: Ten pigs were randomized to either sham irradiation or irradiation
of the atrioventricular junction (55, 50, 40, and 25 Gy). Animals underwent
baseline electrophysiological evaluation, cardiac gated multi-row computed
tomographic imaging for beam delivery planning, and intensity-modulated radiation
therapy. Doses to the coronary arteries were optimized. Invasive follow-up was
conducted <=4 months after the irradiation. A mean volume of 2.5+/-0.5 mL was
irradiated with target dose. The mean follow-up length after irradiation was
124.8+/-30.8 days. Out of 7 irradiated animals, complete atrioventricular block
was achieved in 6 animals of all 4 dose groups (86%). Using the same targeting
margins, ablation lesion size notably increased with the delivered dose because
of volumetric effects of isodose lines around the target volume. The mean
macroscopically calculated atrial lesion volume for all 4 dose groups was 3.8+/
1.1 mL, lesions extended anteriorly into the interventricular septum. No short
term side effects were observed. No damage was observed in the tissues of the
esophagus, phrenic nerves, or trachea. However, histology revealed in-field beam
effects outside of the target volume. CONCLUSIONS: Single-fraction doses as low
as 25 Gy caused a lesion with interruption of cardiac impulse propagation using
this respective target volume. With doses of <=55 Gy, maximal point-doses to
coronary arteries could be kept <7Gy, but target conformity of lesions was not
fully achieved using this approach.
PMID- 28408648
TI - Azithromycin Causes a Novel Proarrhythmic Syndrome.
AB - BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of
cardiovascular and sudden cardiac death, although the underlying mechanisms are
unclear. Case reports, including the one we document here, demonstrate that
azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence
of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated
the electrophysiological effects of azithromycin in vivo and in vitro using mice,
cardiomyocytes, and human ion channels heterologously expressed in human
embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells. METHODS AND
RESULTS: In conscious telemetered mice, acute intraperitoneal and oral
administration of azithromycin caused effects consistent with multi-ion channel
block, with significant sinus slowing and increased PR, QRS, QT, and QTc
intervals, as seen with azithromycin overdose. Similarly, in HL-1 cardiomyocytes,
the drug slowed sinus automaticity, reduced phase 0 upstroke slope, and prolonged
action potential duration. Acute exposure to azithromycin reduced peak SCN5A
currents in HEK cells (IC50=110+/-3 MUmol/L) and Na+ current in mouse ventricular
myocytes. However, with chronic (24 hour) exposure, azithromycin caused a ~2-fold
increase in both peak and late SCN5A currents, with findings confirmed for INa in
cardiomyocytes. Mild block occurred for K+ currents representing IKr (CHO cells
expressing hERG; IC50=219+/-21 MUmol/L) and IKs (CHO cells expressing
KCNQ1+KCNE1; IC50=184+/-12 MUmol/L), whereas azithromycin suppressed L-type Ca++
currents (rabbit ventricular myocytes, IC50=66.5+/-4 MUmol/L) and IK1 (HEK cells
expressing Kir2.1, IC50=44+/-3 MUmol/L). CONCLUSIONS: Chronic exposure to
azithromycin increases cardiac Na+ current to promote intracellular Na+ loading,
providing a potential mechanistic basis for the novel form of proarrhythmia seen
with this macrolide antibiotic.
PMID- 28408651
TI - Disease Severity and Exercise Testing Reduce Subcutaneous Implantable
Cardioverter-Defibrillator Left Sternal ECG Screening Success in Hypertrophic
Cardiomyopathy.
AB - BACKGROUND: The features of the hypertrophic cardiomyopathy (HCM) ECG make it a
challenge for subcutaneous implantable cardioverter-defibrillator (S-ICD)
screening. We aimed to investigate the causes of screening failure at rest and on
exercise to inform optimal S-ICD ECG vector development. METHODS AND RESULTS: One
hundred and thirty-one HCM patients (age, 50+/-16 years; 92 males and 39 females)
with >=1 HCM risk factor for sudden death underwent S-ICD ECG screening at rest
and on exercise. Fifty patients (38%) were ineligible for S-ICD because of
screening failure in every lead vector: 33 (66%) failed in the supine position,
12 (24%) failed in the standing position, and 5 (10%) failed on exercise. In
patients who could exercise and passed screening at rest, 31 (44%) had 1 vector
safety, 16 (23%) had 2 vector safety, and 24 (33%) had 3 vector safety. Increased
R:T wave ratio in the S-ICD screening ECG (odds ratio, 4.0; confidence interval,
3.0-5.3; P<0.001) was associated with screening failure, while R/T ratio <3 in
aVF (odds ratio, 0.3; confidence interval, 0.12-0.69; P=0.006) and increasing age
(odds ratio, 0.97; confidence interval, 0.95-0.99; P=0.03) was associated with
reduced screening failure. European Society of Cardiology risk score was higher
in those failing screening (risk score 5.5% [interquartile range, 3.2-8.7] in
failed versus 4.5% [interquartile range, 2.9-7.4] in passed; P=0.04).
CONCLUSIONS: HCM patients have a significant incidence of screening failure,
which is determined primarily by the increased R:T ratio on the screening ECG and
lead aVF. High-risk patients have an increased screening failure rate.
Optimization of sensing algorithms is required to ensure that the highest risk
HCM patients can benefit from S-ICD implantation.
PMID- 28408653
TI - Drug-Induced Arrhythmias, Precision Medicine, and Small Data.
PMID- 28408652
TI - Premature Ventricular Contraction Coupling Interval Variability Destabilizes
Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous
Cardioneural Mapping.
AB - BACKGROUND: Variability in premature ventricular contraction (PVC) coupling
interval (CI) increases the risk of cardiomyopathy and sudden death. The
autonomic nervous system regulates cardiac electrical and mechanical indices, and
its dysregulation plays an important role in cardiac disease pathogenesis. The
impact of PVCs on the intrinsic cardiac nervous system, a neural network on the
heart, remains unknown. The objective was to determine the effect of PVCs and CI
on intrinsic cardiac nervous system function in generating cardiac neuronal and
electric instability using a novel cardioneural mapping approach. METHODS AND
RESULTS: In a porcine model (n=8), neuronal activity was recorded from a
ventricular ganglion using a microelectrode array, and cardiac
electrophysiological mapping was performed. Neurons were functionally classified
based on their response to afferent and efferent cardiovascular stimuli, with
neurons that responded to both defined as convergent (local reflex processors).
Dynamic changes in neuronal activity were then evaluated in response to right
ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC
delivery elicited a greater neuronal response than all other stimuli (P<0.001).
Compared with fixed short and long CI, PVCs with variable CI had a greater impact
on neuronal response (P<0.05 versus short CI), particularly on convergent neurons
(P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic
input (P<0.05). The greatest cardiac electric instability was also observed after
variable (short) CI PVCs. CONCLUSIONS: Variable CI PVCs affect critical
populations of intrinsic cardiac nervous system neurons and alter cardiac
repolarization. These changes may be critical for arrhythmogenesis and
remodeling, leading to cardiomyopathy.
PMID- 28408654
TI - Radiographic disease progression in contemporary US coal miners with progressive
massive fibrosis.
AB - INTRODUCTION: Among contemporary US coal miners, there has been an increase in
the prevalence and severity of pneumoconiosis, including its advanced form
progressive massive fibrosis (PMF). We examine radiographic progression in Coal
Workers' Health Surveillance Program (CWHSP) participants. METHODS: CWHSP
participants with a final determination of PMF during 1 January 2000-1 October
2016 with at least one prior radiograph in the system were included. We
characterised demographics, participation and progression patterns. RESULTS: A
total of 192 miners with a PMF determination contributed at least one additional
radiograph (total count: 2-10). Mean age at first radiograph was 28.8 years, 162
(84%) worked in Kentucky, Virginia or West Virginia and 169 (88%) worked
exclusively underground. A total of 163 (85%) miners had a normal initial
radiograph. Mean time from most recent normal radiograph to one with a PMF
determination was 20.7 years (range: 1-43) and 27 (17%) progressed to PMF in less
than 10 years. DISCUSSION: Dust exposure is the sole cause of this disease, and a
substantial number of these miners progressed from normal to PMF in less than a
decade. Participation in CWHSP is voluntary, and these findings are influenced by
participation patterns, so for many miners it remains unclear how rapidly their
disease progressed. The National Institute for Occupational Safety and Health
recommends all working miners to participate in radiographic surveillance at 5
year intervals. Improved participation could allow more precise characterisation
of the burden and characteristics of pneumoconiosis in US coal miners and provide
an important early detection tool to prevent cases of severe disease.
PMID- 28408655
TI - Military small arms fire in association with acute decrements in lung function.
AB - OBJECTIVE: After introduction of unleaded ammunition, Norwegian Armed Forces
received reports of acute respiratory symptoms in soldiers after exposure to
fumes from firing the standard weapon, HK416. The aim of the present study was to
examine lung function before and after exposure to fumes from HK416 in a double
blinded standardised study design using three different types of ammunition.
METHODS: Fifty-four healthy, non-smoking male volunteers (19-62 years) fired the
weapons for 60 min with either leaded, unleaded or 'modified' unleaded
ammunition. Gaseous and particulate emissions were monitored. Spirometry and
exhaled nitric oxide (eNO) were performed within 14 days before (T0), shortly
after (T1) and 24 hours after (T2) shooting. Methacholine provocation and
diffusing capacity of carbon monoxide (DLCO) were carried out at T0 and T2.
RESULTS: The mean forced expiratory volume in 1 s on a group level was
significantly reduced both at T1 and T2 compared with T0, with means and 95% CI
of 226 mL (158 to 294 mL) and 285 mL (218 to 351 mL), respectively. The same
significant pattern was seen for DLCO, forced vital capacity and eNO. The
methacholine test indicated a slight increase in bronchial hyper-reactivity.
However, there were no significant differences between types of ammunition used.
CONCLUSION: Exposure to fumes from military weapons might be a respiratory hazard
for soldiers who do live-fire training regularly or are in a closed combat
environment.
PMID- 28408656
TI - Is job rotation effective for prevention of work-related musculoskeletal
disorders and sick leave?
PMID- 28408657
TI - Negative Regulation of Human Pregnane X Receptor by MicroRNA-18a-5p: Evidence for
Suppression of MicroRNA-18a-5p Expression by Rifampin and Rilpivirine.
AB - Small noncoding microRNAs act as post-transcriptional regulators of gene
expression involved in diverse biologic functions. Pregnane X receptor (PXR,
NR1I2), a member of the superfamily of nuclear receptors, is a transcription
factor governing the transport and biotransformation of various drugs and other
chemicals. In the present study, we identified a specific microRNA (miR) involved
in regulating the expression and functionality of human PXR (hPXR). According to
bioinformatics analysis employing three commonly used algorithms (TargetScan,
miRanda, and DIANA-microT-CDS), miR-18a-5p was predicted to be the top candidate
microRNA regulator of hPXR. Consequently, this microRNA was selected for detailed
experimental investigation. As shown in cell-based dual-luciferase reporter gene
assays, functional interaction occurred between miR-18a-5p and the microRNA
recognition element of miR-18a-5p in the 3'-untranslated region of hPXR mRNA.
Transfection of LS180 human colorectal adenocarcinoma cells with an miR-18a-5p
mimic decreased hPXR mRNA and protein expression, whereas transfection of LS180
cells with an miR-18a-5p inhibitor increased hPXR mRNA and protein expression.
The decrease in hPXR expression by the miR-18a-5p mimic was associated with a
reduction in the extent of hPXR target gene (CYP3A4) induction by rifampin and
rilpivirine. Treatment of untransfected LS180 cells with either of these hPXR
agonists decreased endogenous expression of miR-18a-5p, and this preceded the
onset of CYP3A4 induction. In conclusion, miR-18a-5p is a negative regulator of
hPXR expression and the hPXR agonists rifampin and rilpivirine are chemical
suppressors of miR-18a-5p expression.
PMID- 28408658
TI - Meristem Doming and the Transition to Reproductive Development in Tomato.
PMID- 28408659
TI - Chasing Scattered Genes: Identifying Specialized Metabolite Pathway Genes through
Global Coexpression Analysis.
PMID- 28408660
TI - A Global Coexpression Network Approach for Connecting Genes to Specialized
Metabolic Pathways in Plants.
AB - Plants produce diverse specialized metabolites (SMs), but the genes responsible
for their production and regulation remain largely unknown, hindering efforts to
tap plant pharmacopeia. Given that genes comprising SM pathways exhibit
environmentally dependent coregulation, we hypothesized that genes within a SM
pathway would form tight associations (modules) with each other in coexpression
networks, facilitating their identification. To evaluate this hypothesis, we used
10 global coexpression data sets, each a meta-analysis of hundreds to thousands
of experiments, across eight plant species to identify hundreds of coexpressed
gene modules per data set. In support of our hypothesis, 15.3 to 52.6% of modules
contained two or more known SM biosynthetic genes, and module genes were enriched
in SM functions. Moreover, modules recovered many experimentally validated SM
pathways, including all six known to form biosynthetic gene clusters (BGCs). In
contrast, bioinformatically predicted BGCs (i.e., those lacking an associated
metabolite) were no more coexpressed than the null distribution for neighboring
genes. These results suggest that most predicted plant BGCs are not genuine SM
pathways and argue that BGCs are not a hallmark of plant specialized metabolism.
We submit that global gene coexpression is a rich, largely untapped resource for
discovering the genetic basis and architecture of plant natural products.
PMID- 28408663
TI - Permanent Draft Genome Sequence of Desulfurococcus amylolyticus Strain Z-533T, a
Peptide and Starch Degrader Isolated from Thermal Springs in the Kamchatka
Peninsula and Kunashir Island, Russia.
AB - Desulfurococcus amylolyticus Z-533T, a hyperthermophilic crenarcheon, ferments
peptide and starch, generating acetate, isobutyrate, isovalerate, CO2, and
hydrogen. Unlike D. amylolyticus Z-1312, it cannot use cellulose and is inhibited
by hydrogen. The reported draft genome sequence of D. amylolyticus Z-533T will
help to understand the molecular basis for these differences.
PMID- 28408662
TI - The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein
Landscape Identifies Raptor Phosphorylation Required for Spermatogonial
Progenitor Cell Proliferation.
AB - Cytokine-dependent renewal of stem cells is a fundamental requisite for tissue
homeostasis and regeneration. Spermatogonial progenitor cells (SPCs) including
stem cells support life-long spermatogenesis and male fertility, but pivotal
phosphorylation events that regulate fate decisions in SPCs remain unresolved.
Here, we described a quantitative mass-spectrometry-based proteomic and
phosphoproteomic analyses of SPCs following sustained stimulation with glial cell
derived neurotrophic factor (GDNF), an extrinsic factor supporting SPC
proliferation. Stimulated SPCs contained 3382 identified phosphorylated proteins
and 12141 phosphorylation sites. Of them, 325 differentially phosphorylated
proteins and 570 phosphorylation sites triggered by GDNF were highly enriched for
ERK1/2, GSK3, CDK1, and CDK5 phosphorylating motifs. We validated that inhibition
of GDNF/ERK1/2-signaling impaired SPC proliferation and increased G2/M cell cycle
arrest. Significantly, we found that proliferation of SPCs requires
phosphorylation of the mTORC1 component Raptor at Ser863 Tissue-specific deletion
of Raptor in mouse germline cells results in impaired spermatogenesis and
progressive loss of spermatogonia, but in vitro increased phosphorylation of
Raptor by raptor over-expression in SPCs induced a more rapidly growth of SPCs in
culture. These findings implicate previously undescribed signaling networks in
governing fate decision of SPCs, which is essential for the understanding of
spermatogenesis and of potential consequences of pathogenic insult for male
infertility.
PMID- 28408661
TI - Multi-Omics of Tomato Glandular Trichomes Reveals Distinct Features of Central
Carbon Metabolism Supporting High Productivity of Specialized Metabolites.
AB - Glandular trichomes are metabolic cell factories with the capacity to produce
large quantities of secondary metabolites. Little is known about the connection
between central carbon metabolism and metabolic productivity for secondary
metabolites in glandular trichomes. To address this gap in our knowledge, we
performed comparative metabolomics, transcriptomics, proteomics, and 13C-labeling
of type VI glandular trichomes and leaves from a cultivated (Solanum lycopersicum
LA4024) and a wild (Solanum habrochaites LA1777) tomato accession. Specific
features of glandular trichomes that drive the formation of secondary metabolites
could be identified. Tomato type VI trichomes are photosynthetic but acquire
their carbon essentially from leaf sucrose. The energy and reducing power from
photosynthesis are used to support the biosynthesis of secondary metabolites,
while the comparatively reduced Calvin-Benson-Bassham cycle activity may be
involved in recycling metabolic CO2 Glandular trichomes cope with oxidative
stress by producing high levels of polyunsaturated fatty acids, oxylipins, and
glutathione. Finally, distinct mechanisms are present in glandular trichomes to
increase the supply of precursors for the isoprenoid pathways. Particularly, the
citrate-malate shuttle supplies cytosolic acetyl-CoA and plastidic glycolysis and
malic enzyme support the formation of plastidic pyruvate. A model is proposed on
how glandular trichomes achieve high metabolic productivity.
PMID- 28408664
TI - Complete Genome Sequence of a Novel Porcine Circovirus Type 3 Strain,
PCV3/CN/Hubei-618/2016, Isolated from China.
AB - In October 2016, porcine circovirus type 3 (PCV3) was identified as a pathogen
agent for pigs in the United States. Here, we report the genome sequence of a
Chinese PCV3 strain, PCV3/CN/Hubei-618/2016. This will help us better understand
the epidemiology and genetic characteristics of PCV3.
PMID- 28408665
TI - Draft Genome Sequences of 13 Colombian Helicobacter pylori Strains Isolated from
Pacific Coast and Andean Residents.
AB - We present here the draft genomes of 13 Helicobacter pylori strains isolated from
Colombian residents on the Pacific coast (n = 6) and in the Andes mountains (n =
7), locations that differ in gastric cancer risk. These 13 strains were obtained
from individuals with diagnosed gastric lesions.
PMID- 28408666
TI - Draft Genome Sequence of Chryseobacterium sp. JV274 Isolated from Maize
Rhizosphere.
AB - We report the draft genome sequence of Chryseobacterium sp. JV274. This strain
was isolated from the rhizosphere of maize during a greenhouse experiment. JV274
harbors genes involved in flexirubin production (darA and darB genes), bacterial
competition (type VI secretion system), and gliding (bacterial motility; type IX
secretion system).
PMID- 28408667
TI - Draft Genome Sequence of Roseomonas mucosa Strain AU37, Isolated from a
Peripheral Intravenous Catheter.
AB - Roseomonas mucosa is an opportunistic pathogen that causes infections in humans
and is often associated with vascular catheter-related bacteremia. Here, we
report the draft genome sequence of Roseomonas mucosa strain AU37, isolated from
a peripheral intravenous catheter tip.
PMID- 28408668
TI - Genome Sequence of Cobetia sp. Strain MM1IDA2H-1, a Hydrocarbon-Degrading and
Biosurfactant-Producing Marine Bacterium.
AB - Cobetia sp. strain MM1IDA2H-1 is a marine bacterium isolated from seawater
samples that uses the heterocyclic aromatic hydrocarbon dibenzothiophene as the
sole carbon source and produces a biosurfactant that inhibits bacterial quorum
sensing. The Cobetia sp. MM1IDA2H-1 genome was sequenced, processed, assembled,
and annotated for basic and applied studies.
PMID- 28408669
TI - Draft Genome Sequence of Permafrost Bacterium Nesterenkonia sp. Strain PF2B19,
Revealing a Cold Adaptation Strategy and Diverse Biotechnological Potential.
AB - Nesterenkonia sp. strain PF2B19, a psychrophilic bacterium, was isolated from
44,800-year-old permafrost. The draft genome sequence of this strain revealed the
presence of genes involved in the production of cold active enzymes, carotenoid
biosynthesis, fatty acid biosynthesis, and resistance to heavy metals. These
results show the immense potential of the strain.
PMID- 28408670
TI - Insights into the Psychrophilic and Sea Ice-Specific Lifestyle of Marinobacter
sp. Strain AC-23: a Genomic Approach.
AB - Marinobacter sp. strain AC-23 was isolated from Kongsfjorden in the Arctic. Here,
we report the first draft genome sequence of a putative novel species of the
genus Marinobacter comprising 4,149,715 bp, with a mean G+C content of 54.4%. The
draft genome sequence will aid in understanding the psychrophilic and sea ice
specific lifestyle.
PMID- 28408671
TI - Complete Genome Sequences of Chikungunya Viruses Isolated from Plasma Specimens
Collected from Haitians in 2014.
AB - Ten chikungunya virus isolates from human plasma collected in Haiti from May to
August 2014, in the midst of a chikungunya fever outbreak, were fully sequenced.
The resulting genomic sequences are nearly identical, and phylogenetic analyses
indicate they belong to the Asian lineage of the virus.
PMID- 28408672
TI - The Genome Sequence of Avibacterium paragallinarum Strain CL Has a Large
Repertoire of Insertion Sequence Elements.
AB - The draft genome sequence of Avibacterium paragallinarum strain CL serovar C is
reported here. The genome comprises 154 contigs corresponding to 2.4 Mb with 41%
G+C content and many insertion sequence (IS) elements, a characteristic not
previously reported in A. paragallinarum.
PMID- 28408673
TI - Draft Genome Sequence of Methicillin-Resistant Staphylococcus aureus Strain LC33
Isolated from Human Breast Milk.
AB - Here, we report the draft genome sequence of Staphylococcus aureus strain LC33,
isolated from human breast milk in Brazil. This microorganism has been typed as
ST1/t127/sccmecV. To our knowledge, this is the first draft genome sequence of a
methicillin-resistant S. aureus strain isolated from human breast milk.
PMID- 28408674
TI - Complete Genome Sequence of Mycobacterium sp. MS1601, a Bacterium Performing
Selective Oxidation of Polyols.
AB - Corynebacterium sp. (ATCC 21245) is reclassified here as Mycobacterium sp. MS1601
based on 16S rRNA gene and complete-genome sequence analysis. It is able to
oxidize branched polyols to corresponding hydroxycarboxylic acids. The total size
of the genome sequence was 6,829,132 bp, including one circular chromosome of
6,407,860 bp.
PMID- 28408675
TI - Draft Genome Sequences of Two Clinical Methicillin-Resistant Staphylococcus
aureus Strains Isolated from Healthy Children in Brazil.
AB - We report here the draft genome sequences of two community-associated methicillin
resistant Staphylococcus aureus (CA-MRSA) strains, C18 and C80, isolated from
healthy children from day care centers. To our knowledge, these are the first
draft genome sequences of CA-MRSA ST398/CC398/SccmecV and CA-MRSA
ST5/CC5/SccmecIVa isolated from healthy children in Brazil.
PMID- 28408676
TI - Complete Genome Sequence of Human Norovirus GII.Pe-GII.4 Sydney from the United
States.
AB - We report here the first near-complete genome sequence (7,551 nucleotides) of a
human norovirus GII.Pe-GII.4 Sydney variant, detected in a stool sample from an
outbreak on a cruise ship in 2013.
PMID- 28408677
TI - Genome Sequence of Pasteurella multocida Razi 0002 of Avian Origin.
AB - We report here on the genome sequence of Pasteurella multocida Razi 0002 of avian
origin, isolated in Iran. The genome has a size of 2,289,036 bp, a G+C content of
40.3%, and is predicted to contain 2,079 coding sequences.
PMID- 28408678
TI - Draft Genome Sequence of a Kale (Brassica oleracea L.) Root Endophyte,
Pseudomonas sp. Strain C9.
AB - Pseudomonas sp. strain C9 is a plant growth-promoting bacterium isolated from the
root tissue of Brassica oleracea L. grown in soil from Marlborough, New Zealand.
Its draft genome of 6,350,161 bp contains genes associated with plant growth
promotion and biological control.
PMID- 28408679
TI - Complete Genome Sequence of Komagataeibacter hansenii Strain HUM-1.
AB - This study reports the release of the complete nucleotide sequence of
Komagataeibacter hansenii HUM-1, a new efficient producer of cellulose.
Elucidation of the genome may provide more information to aid in understanding
the genes necessary for cellulose biosynthesis.
PMID- 28408680
TI - Complete Genome Sequence of Komagataeibacter hansenii LMG 23726T.
AB - This study reports the release of the complete nucleotide sequence of
Komagataeibacter hansenii LMG 23726T This organism is a cellulose producer, and
its genome may provide more information to aid in the understanding of the genes
necessary for cellulose biosynthesis.
PMID- 28408681
TI - Complete Genome Sequence of Komagataeibacter hansenii Strain SC-3B.
AB - This study reports the release of the complete nucleotide sequence of
Komagataeibacter hansenii SC-3B, a new efficient producer of cellulose.
Elucidation of the genome may provide more information to aid in understanding
the genes necessary for cellulose biosynthesis.
PMID- 28408682
TI - Draft Whole-Genome Sequence of "Candidatus Liberibacter asiaticus" Strain TX2351
Isolated from Asian Citrus Psyllids in Texas, USA.
AB - We report here the draft genome sequence of "Candidatus Liberibacter asiaticus"
strain TX2351, collected from Asian citrus psyllids in south Texas, USA. The
TX2351 genome has a size of 1,252,043 bp, a G+C content of 36.5%, 1,184 predicted
open reading frames, and 52 RNA genes.
PMID- 28408683
TI - Draft Genome Sequence of Multidrug-Resistant Abortive Campylobacter jejuni from
Northern California.
AB - Campylobacter jejuni is an enteric bacterium that can cause abortion in
livestock. This is the release of a multidrug-resistant Campylobacter jejuni
genome from an isolate that caused an abortion in a cow in northern California.
This isolate is part of the 100K Pathogen Genome Project.
PMID- 28408684
TI - Draft Genome Sequence of the Fish Pathogen Flavobacterium columnare Strain CSF
298-10.
AB - We announce here the draft genome assembly of Flavobacterium columnare CSF-298
10, a strain isolated from an outbreak of columnaris disease at a commercial
trout farm in Hagerman Valley, Idaho, USA. The complete genome consists of 13
contigs totaling 3,284,579 bp, with an average G+C content of 31.5% and 2,933
predicted coding genes.
PMID- 28408685
TI - Permanent Draft Genome Sequences of Three Frankia sp. Strains That Are Atypical,
Noninfective, Ineffective Isolates.
AB - Here, we present draft genome sequences for three atypical Frankia strains
(lineage 4) that were isolated from root nodules but are unable to reinfect
actinorhizal plants. The genome sizes of Frankia sp. strains EUN1h, BMG5.36, and
NRRL B16386 were 9.91, 11.20, and 9.43 Mbp, respectively.
PMID- 28408686
TI - Permanent Draft Genome Sequence of the French Bean Symbiont Rhizobium sp. Strain
RSm-3 Isolated from the Eastern Himalayan Region of India.
AB - The genus Rhizobium contains many species able to form nitrogen-fixing nodules on
plants of the legume family. Here, we report the 6.9-Mbp draft genome sequence of
Rhizobium sp. strain RSm-3, with a G+C content of 61.4% and 6,511 candidate
protein-coding genes.
PMID- 28408687
TI - Drifted Influenza A and B Viruses Collected by a Water-Based Condensation Growth
Air Sampler in a Student Health Care Center during an Influenza Outbreak.
AB - A viable virus aerosol sampler (VIVAS) effectively collected viable influenza A
and B viruses from air inside a student health care center during an influenza
outbreak. The viruses had "drifted" genes, showcasing the usefulness of the VIVAS
for air sampling and noninvasive surveillance of viruses in circulation.
PMID- 28408688
TI - Draft Genome Sequence of Streptomyces sp. JHA26, a Strain That Harbors a PA14
Domain Containing beta-d-Galactofuranosidase.
AB - The genome sequence of Streptomyces sp. strain JHA26, the culture supernatant of
which exhibited beta-d-galactofuranosidase (Galf-ase) activity, was analyzed to
search for a Galf-ase-encoding gene. We report here the results of whole-genome
shotgun sequencing and reveal the identity of a new Galf-ase gene.
PMID- 28408689
TI - Draft Genome Sequences of Four Yersinia enterocolitica Strains, Isolated from
Wild Ungulate Carcasses.
AB - This study describes the draft genome sequences of four Yersinia enterocolitica
strains, originally isolated from ungulate carcasses. These isolates were typed
biochemically and two were determined to be highly virulent (biotype 1B). The
draft genome sequences had a mean size of 4.77 Mb and a mean G+C content of
47.1%.
PMID- 28408690
TI - Draft Genome Sequences of Tetragenococcus muriaticus Strains 3MR10-3 and PMC-11-5
Isolated from Thai Fish Sauce during Natural Fermentation.
AB - Tetragenococcus muriaticus strains 3MR10-3 and PMC-11-5 are homofermentative
halophilic lactic acid bacteria isolated from Thai fish sauce during natural
fermentation. Their draft genomes were sequenced. Our interest in these organisms
is related to their impact on fish sauce flavor and their high osmotolerance.
PMID- 28408691
TI - Whole-Genome Sequence of Staphylococcus hominis Strain J31 Isolated from Healthy
Human Skin.
AB - We report here the first whole-genome sequence of a skin-associated strain of
Staphylococcus hominis determined using the PacBio long-read sequencing platform.
S. hominis is a major commensal of the skin microflora. This genome sequence adds
to our understanding of this species and will aid studies of gene traffic between
staphylococci.
PMID- 28408692
TI - Draft Genome Sequences of Several Fungal Strains Selected for Exposure to
Microgravity at the International Space Station.
AB - The whole-genome sequences of eight fungal strains that were selected for
exposure to microgravity at the International Space Station are presented here.
These baseline sequences will help to understand the observed production of novel
bioactive compounds.
PMID- 28408693
TI - Complete Genome Sequences of Porcine Parvovirus 2 Isolated from Swine in the
Republic of Korea.
AB - Here, we report sequences of the porcine parvovirus 2 (PPV2) genome, isolated
from pigs in the Republic of Korea in 2016. The sequences of open reading frames
1 and 2 (ORF1 and ORF2) had a 98.8 to 98.9% homology with the US135 strain and
98.8% homology with the US523 strain, respectively. This is the first study to
report the PPV2 genome in South Korean pigs.
PMID- 28408694
TI - Determinants of hypoxia-inducible factor activity in the intestinal mucosa.
AB - The intestinal mucosa is exposed to fluctuations in oxygen levels due to
constantly changing rates of oxygen demand and supply and its juxtaposition with
the anoxic environment of the intestinal lumen. This frequently results in a
state of hypoxia in the healthy mucosa even in the physiologic state.
Furthermore, pathophysiologic hypoxia (which is more severe and extensive) is
associated with chronic inflammatory diseases including inflammatory bowel
disease (IBD). The hypoxia-inducible factor (HIF), a ubiquitously expressed
regulator of cellular adaptation to hypoxia, is central to both the adaptive and
the inflammatory responses of cells of the intestinal mucosa in IBD patients. In
this review, we discuss the microenvironmental factors which influence the level
of HIF activity in healthy and inflamed intestinal mucosae and the consequences
that increased HIF activity has for tissue function and disease progression.
PMID- 28408695
TI - Effect of exercise timing on elevated postprandial glucose levels.
AB - There is no consensus regarding optimal exercise timing for reducing postprandial
glucose (PPG). The purpose of the present study was to determine the most
effective exercise timing. Eleven participants completed four different exercise
patterns 1) no exercise; 2) preprandial exercise (jogging); 3) postprandial
exercise; and 4) brief periodic exercise intervention (three sets of 1-min
jogging + 30 s of rest, every 30 min, 20 times total) in a random order separated
by a minimum of 5 days. Preprandial and postprandial exercise consisted of 20
sets of intermittent exercise (1 min of jogging + 30 s rest per set) repeated 3
times per day. Total daily exercise volume was identical for all three exercise
patterns. Exercise intensities were 62.4 +/- 12.9% Vo2peak Blood glucose
concentrations were measured continuously throughout each trial for 24 h. After
breakfast, peak blood glucose concentrations were lower with brief periodic
exercise (99 +/- 6 mg/dl) than those with preprandial and postprandial exercise
(109 +/- 10 and 115 +/- 14 mg/dl, respectively, P < 0.05, effect size = 0.517).
After lunch, peak glucose concentrations were lower with brief periodic exercise
than those with postprandial exercise (97 +/- 5 and 108 +/- 8 mg/dl, P < 0.05,
effect size = 0.484). After dinner, peak glucose concentrations did not
significantly differ among exercise patterns. Areas under the curve over 24 h and
2 h postprandially did not differ among exercise patterns. These findings suggest
that brief periodic exercise may be more effective than preprandial and
postprandial exercise at attenuating PPG in young active individuals.NEW &
NOTEWORTHY This was the first study to investigate the effect of different
exercise timing (brief periodic vs. preprandial vs. postprandial exercise) on
postprandial glucose (PPG) attenuation in active healthy men. We demonstrated
that brief periodic exercise attenuated peak PPG levels more than preprandial and
postprandial exercise, particularly in the morning. Additionally, PPG rebounded
soon after discontinuing postprandial exercise. Thus, brief periodic exercise may
be better than preprandial and postprandial exercise at attenuating PPG levels.
PMID- 28408696
TI - Assessment of tongue mechanical properties using different contraction tasks.
AB - Inadequate upper airway (UA) dilator muscle function may play an important role
in the pathophysiology of obstructive sleep apnea (OSA). To date, tongue
mechanical properties have been assessed mainly using protrusion protocol with
conflicting results. Performance during elevation tasks among patients with OSA
remains unknown. This study aimed at assessing tongue muscle strength, strength
stability, endurance time, fatigue indices, and total muscle work, using
elevation and protrusion tasks with repetitive isometric fatiguing contractions
in 12 normal plus mild, 17 moderate, and 11 severe patients with OSA, and to
assess the influence of body mass index (BMI) and age. Endurance time was longer
in protrusion than elevation task (P = 0.01). In both tasks, endurance time was
negatively correlated with baseline value of strength coefficient of variation (P
< 0.01). Compared with other groups, patients with moderate OSA had the lowest
total muscle work for protrusion (P = 0.01) and shortest endurance time (P =
0.04), regardless of the type of task. Additionally, in patients with moderate
severe OSA, the total muscle work for both tasks was lower in nonobese compared
with obese (P < 0.05). Total muscle work for protrusion was positively correlated
with apnea hypopnea index (AHI) in obese subjects (P < 0.01). Endurance time was
shorter (P < 0.01) and recovery time longer (P = 0.02) in the old compared with
young subjects. In conclusion, the tongue is more prone to fatigue during the
elevation task and in patients with moderate OSA. Obesity appeared to prevent
alteration of tongue mechanical properties in patients with OSA. Baseline
strength stability and endurance were related, illustrating the role of central
neuromuscular output in tongue resistance to fatigue.NEW & NOTEWORTHY To our
knowledge, this is the first study to assess and compare tongue function using
both elevation and protrusion tasks with repetitive isometric fatiguing
contractions in subjects with different OSA status. Tongue mechanical performance
seemed to differ between protrusion and elevation tasks and depend on the
severity of OSA.
PMID- 28408697
TI - Combined effect of Bacillus coagulans GBI-30, 6086 and HMB supplementation on
muscle integrity and cytokine response during intense military training.
AB - The purpose of this study was to compare the coadministration of the probiotic
Bacillus coagulans GBI-30, 6086 (BC30) with beta-hydroxy-beta-methylbutyrate
(HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle
integrity during 40 days of intense military training. Soldiers were randomly
assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with
placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL;
n = 8). During the first 28 days soldiers were garrisoned on base and
participated in the same training tasks. During the final 2 wk soldiers navigated
25-30 km per night in difficult terrain carrying ~35 kg of equipment. All
assessments (blood draws and diffusion tensor imaging to assess muscle integrity)
were conducted before and ~12 h after final supplement consumption. Analysis of
covariance was used to analyze all blood and muscle measures. Significant
attenuations were noted in IL-1beta, IL-2, IL-6, CX3CL1, and TNF-alpha for both
CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were
significantly attenuated for CaHMBBC30 compared with CTL only. A significant
decrease in apparent diffusion coefficients was also observed for CaHMBBC30
compared with CaHMBPL. Results provide further evidence that HMB supplementation
may attenuate the inflammatory response to intense training and that the
combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB
alone in maintaining muscle integrity during intense military training.NEW &
NOTEWORTHY beta-Hydroxy-beta-methylbutyrate (HMB) in its free acid form was
reported to attenuate inflammation and maintain muscle integrity during military
training. However, this formulation was difficult to maintain in the field. In
this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans
(BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB
attenuated the inflammatory response and that BC30 combined with CaHMB may be
more beneficial than CaHMB alone in maintaining muscle integrity during intense
military training.
PMID- 28408698
TI - Reproducibility of Lobar Perfusion and Ventilation Quantification Using SPECT/CT
Segmentation Software in Lung Cancer Patients.
AB - Planar perfusion scintigraphy with 99mTc-labeled macroaggregated albumin is often
used for pretherapy quantification of regional lung perfusion in lung cancer
patients, particularly those with poor respiratory function. However, subdividing
lung parenchyma into rectangular regions of interest, as done on planar images,
is a poor reflection of true lobar anatomy. New tridimensional methods using
SPECT and SPECT/CT have been introduced, including semiautomatic lung
segmentation software. The present study evaluated inter- and intraobserver
agreement on quantification using SPECT/CT software and compared the results for
regional lung contribution obtained with SPECT/CT and planar scintigraphy.
Methods: Thirty lung cancer patients underwent ventilation-perfusion scintigraphy
with 99mTc-macroaggregated albumin and 99mTc-Technegas. The regional lung
contribution to perfusion and ventilation was measured on both planar
scintigraphy and SPECT/CT using semiautomatic lung segmentation software by 2
observers. Interobserver and intraobserver agreement for the SPECT/CT software
was assessed using the intraclass correlation coefficient, Bland-Altman plots,
and absolute differences in measurements. Measurements from planar and
tridimensional methods were compared using the paired-sample t test and mean
absolute differences. Results: Intraclass correlation coefficients were in the
excellent range (above 0.9) for both interobserver and intraobserver agreement
using the SPECT/CT software. Bland-Altman analyses showed very narrow limits of
agreement. Absolute differences were below 2.0% in 96% of both interobserver and
intraobserver measurements. There was a statistically significant difference
between planar and SPECT/CT methods (P < 0.001) for quantification of perfusion
and ventilation for all right lung lobes, with a maximal mean absolute difference
of 20.7% for the right middle lobe. There was no statistically significant
difference in quantification of perfusion and ventilation for the left lung lobes
using either method; however, absolute differences reached 12.0%. The total right
and left lung contributions were similar for the two methods, with a mean
difference of 1.2% for perfusion and 2.0% for ventilation. Conclusion:
Quantification of regional lung perfusion and ventilation using SPECT/CT-based
lung segmentation software is highly reproducible. This tridimensional method
yields statistically significant differences in measurements for right lung lobes
when compared with planar scintigraphy. We recommend that SPECT/CT-based
quantification be used for all lung cancer patients undergoing pretherapy
evaluation of regional lung function.
PMID- 28408699
TI - A Novel 141Ce-Based Flood Field Phantom: Assessment of Suitability for Daily
Uniformity Testing in a Clinical Nuclear Medicine Department.
AB - Daily quality control testing of a gamma-camera is of the utmost importance in
assessing whether the camera is suitable for clinical use. The aim of our study
was to assess the suitability of a fillable 141Ce-based flood field phantom
developed in-house for daily quality control testing of gamma-cameras. Methods:
Daily uniformity testing was performed for 113 d using the fillable 141Ce phantom
and a commercially available sheet-type 57Co phantom, and the results were
compared. Results: The average integral uniformity obtained by the 141Ce and 57Co
phantoms was 3.24% and 2.72%, respectively, for detector 1 and 3.31% and 2.78%,
respectively, for detector 2. Conclusion: The 141Ce phantom we developed is a
suitable alternative to the commercially available 57Co phantom.
PMID- 28408700
TI - Contamination, a Major Problem in Nuclear Medicine Imaging: How to Investigate,
Handle, and Avoid It.
AB - We present a case study in which artifacts from collimator contamination and
patient motion were seen on a bone scan. Any identified artifact must be further
investigated and documented so as to detect its source and thus prevent its
future occurrence.
PMID- 28408701
TI - Mucoepidermoid Parotid Gland Tumor Found on Follow-up Radioiodine Scan for
Differentiated Papillary Thyroid Cancer.
AB - This report presents a case of focal uptake in the right parotid gland found on a
follow-up whole-body radioiodine scan 1 y after successful ablation of
differentiated papillary thyroid carcinoma. After the parotid tumor had been
excised, it was proven histopathologically to be a low-grade mucoepidermoid
tumor. This case illustrates a 131I focus that was false-positive for thyroid
carcinoma. The short period between radioiodine treatment and development of this
parotid tumor creates doubt about a causal relationship. Induction of salivary
gland tumors by radiation has been reported primarily in the setting of external
radiotherapy. In the large volume of thyroid carcinoma patients treated with
radioiodine across the world, such an occurrence has been rare.
PMID- 28408702
TI - A Bizarre Ring Artifact on SPECT/CT Images.
AB - We encountered a round artifact on images obtained with our SPECT/CT system: a
small dark spot surrounded by a broad light ring. The artifact was due to a
problem with the SPECT portion of the hybrid system and was successfully removed
through servicing of the system. This case report describes this scanner-based
artifact, which, to our knowledge, has not previously been reported in the
literature.
PMID- 28408703
TI - Accuracy of 82Rb PET/CT Myocardial Perfusion Imaging with Regadenoson Stress,
Including 3-Year Clinical Outcomes.
AB - The purpose of this study was to determine the clinical accuracy of 82Rb PET/CT
myocardial perfusion imaging (MPI) when performed with regadenoson stress in a
U.S. Department of Veterans Affairs (VA) population of patients. Methods: The
initial cohort of 480 patients undergoing vasodilator PET MPI with regadenoson
stress at our institution from September 2009 through July 2010 was closely
tracked for short-term outcomes based on correlation with invasive coronary
catheterization. Long-term outcomes were determined by major adverse cardiac
event rates based on data extraction from the electronic medical record and
grouped by summed stress score (SSS) for a 3-y period. Results: At the 3-y follow
up, there had been 31 patient deaths, 5 of which were heart-related. Twenty-four
patients had documented myocardial infarctions. Event rates and cardiac death
rates were highly predicted by the results of PET MPI. Seventy patients underwent
invasive cardiac catheterization within 60 d of the PET MPI. Patients were
increasingly likely to undergo catheterization as their SSS increased.
Catheterization correlation demonstrated a sensitivity of 95%, a positive
predictive value of 88.4% for significant coronary artery disease, and an overall
accuracy of 86% for PET MPI with regadenoson stress when compared with invasive
catheterization. Conclusion: PET MPI with regadenoson stress demonstrates high
accuracy when correlated with invasive catheterization and clinical outcomes. The
SSS was highly predictive of cardiac events and patient survival in a VA
population over a 3-y period of clinical follow-up.
PMID- 28408704
TI - Changes in Patterns of 99mTc-Macroaggregated Albumin Use Between 2000 and 2015.
AB - Since the early 2000s, the method of evaluating pulmonary embolism has shifted
from 99mTc-macroaggregated albumin (MAA) perfusion lung scans to CT angiography.
99mTc-MAA continues to be applied for patients with contraindications to CT
angiography and for other uses. A reduced number of 99mTc-MAA particles is
administered to patients with pulmonary hypertension or other risk factors. This
study assessed the changing patterns of 99mTc-MAA use between 2000 and 2015 at a
single institution by comparing snapshots of the procedures performed in those
two years. Methods: Records for all patients receiving 99mTc-MAA in 2000 and 2015
were reviewed, making note of the type of imaging procedure, whether there was
any contraindication to CT angiography, and whether a reduced number of 99mTc-MAA
particles was administered. Results: In 2000, 99mTc-MAA was used for 489 lung
scans for pulmonary embolism, 2 for peritoneovenous shunts, and 1 for a cardiac
shunt. Of the lung scan patients, 46 (9%) had pulmonary hypertension. A reduced
number of particles was administered to the pulmonary hypertension and cardiac
shunt patients (47/492, or 9%). In 2015, 99mTc-MAA was used for 263 lung scans
for pulmonary embolism, 33 for presurgical planning, 33 for patients with a lung
transplant, 16 for pulmonary artery stenosis, 5 to determine hepatic artery
microsphere eligibility, and 1 for a peritoneovenous shunt. Of the lung scans for
pulmonary embolism, 256 of the 263 patients (97%) had a contraindication to CT
angiography or a nondiagnostic CT angiogram, including 99 (38%) with pulmonary
hypertension. A reduced number of particles was administered to the pulmonary
hypertension patients, presurgical patients, and lung-transplant patients
(165/351, or 47%). Conclusion: Comparing 2015 with 2000, lung scans for pulmonary
embolism decreased 46%, from 489 to 263, apparently because of a shift to CT
angiography, whereas other uses rose from 3 to 88. Administration of a reduced
number of particles rose significantly from 9% to 47% of 99mTc-MAA doses.
Although the total number of 99mTc-MAA doses dropped 29%, from 492 to 351, 99mTc
MAA remains an important radiopharmaceutical for both pulmonary embolism and
other uses.
PMID- 28408705
TI - Time-lapse imaging of cleavage divisions in embryo quality assessment.
AB - In vitro fertilization (IVF) is one of the most important procedures for treating
infertility. As several embryos are usually produced in a single IVF cycle, it is
crucial to select only the most viable ones for transfer to the patient.
Morphokinetics, i.e. analysis of the dynamics of cleavage divisions and processes
such as compaction and cavitation, has provided both biologists and clinicians
with a new set of data regarding embryonic behaviour during preimplantation
development and its association with embryo quality. In the current review, we
focus on biological significance of morphokinetic parameters and show how they
can be used to predict a reproductive outcome. We also explain the statistics
behind the predictive algorithms and discuss the future perspectives of
morphokinetics.
PMID- 28408706
TI - Embryo culture in presence of oviductal fluid induces DNA methylation changes in
bovine blastocysts.
AB - During the transit through the oviduct, the early embryo initiates an extensive
DNA methylation reprogramming of its genome. Given that these epigenetic
modifications are susceptible to environmental factors, components present in the
oviductal milieu could affect the DNA methylation marks of the developing embryo.
The aim of this study was to examine if culture of bovine embryos with oviductal
fluid (OF) can induce DNA methylation changes at specific genomic regions in the
resulting blastocysts. In vitro produced zygotes were cultured in medium with 3
mg/mL bovine serum albumin (BSA) or 1.25% OF added at the one- to 16-cell stage
(OF1-16), one- to 8-cell stage (OF1-8) or 8- to 16-cell stage (OF8-16), and then
were cultured until Day 8 in medium with 3 mg/mL BSA. Genomic regions in four
developmentally important genes (MTERF2, ABCA7, OLFM1, GMDS) and within LINE-1
retrotransposons were selected for methylation analysis by bisulfite sequencing
on Day 7-8 blastocysts. Blastocysts derived from OF1-16 group showed lower CpG
methylation levels in MTERF2 and ABCA7 compared with the BSA group. However, CpG
sites within MTERF2, ABCA7 and OLFM1 showed higher methylation levels in groups
OF1-8 and OF8-16 than in OF1-16. For LINE-1 elements, higher CpG methylation
levels were observed in blastocysts from the OF1-16 group than in the other
experimental groups. In correlation with the methylation changes observed, mRNA
expression level of MTERF2 was increased, while LINE-1 showed a decreased
expression in blastocysts from OF1-16 group. Our results suggest that embryos
show transient sensitivity to OF at early stages, which is reflected by specific
methylation changes at the blastocyst stage.
PMID- 28408708
TI - Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and
Clinical Implications.
AB - BACKGROUND: Yield of causative variants in hypertrophic cardiomyopathy (HCM) is
increased in some probands, suggesting different clinical subgroups of disease
occur. We hypothesized that a negative family history and no sarcomere mutations
represent a nonfamilial subgroup of HCM. We sought to determine the prevalence,
natural history, and potential clinical implications of this nonfamilial subgroup
of HCM. METHODS AND RESULTS: Four hundred and thirteen unrelated probands with
HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing
performed were included in this retrospective cohort study. There were 251 (61%)
probands with no reported family history of HCM, including 166 (40% of total)
probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family
pedigree data revealed no difference in mean number of first-degree relatives
screened between nonfamilial and sarcomere-positive groups. Adjusted predictors
of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval,
1.02-1.06; P=0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11
3.45; P=0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57
5.00; P=0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95%
confidence interval, 1.64-7.08; P=0.001). They had a less severe clinical course
with greater event-free survival from major cardiac events (P=0.04) compared with
sarcomere-positive HCM probands. Genotype prediction scores showed good
performance in identifying genotype-positive patients (area under the curve, 0.71
0.75) and, in combination with pedigree characteristics, were further improved.
CONCLUSIONS: Approximately 40% of HCM probands have a nonfamilial subtype, with
later onset and less severe clinical course. We propose a revised clinical
pathway for management, highlighting the role of genetic testing, a detailed
pedigree, and refined clinical surveillance recommendations for family members.
PMID- 28408707
TI - Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events
Among African Americans in 2 Large Cohort Studies.
AB - BACKGROUND: Local ancestry may contribute to the disproportionate burden of
subclinical and clinical cardiovascular disease among admixed African Americans
compared with other populations, suggesting a rationale for admixture mapping.
METHODS AND RESULTS: We estimated local European ancestry (LEA) using Local
Ancestry inference in adMixed Populations using Linkage Disequilibrium method
(LAMP-LD) and evaluated the association with common carotid artery intima-media
thickness (cCIMT) using multivariable linear regression analysis among 1554
African Americans from MESA (Multi-Ethnic Study of Atherosclerosis). We conducted
secondary analysis to examine the significant cCIMT-LEA associations with
clinical cardiovascular disease events. We observed genome-wide significance in
relation to cCIMT association with the SERGEF gene (secretion-regulating guanine
nucleotide exchange factor; beta=0.0137; P=2.98*10-4), also associated with
higher odds of stroke (odds ratio=1.71; P=0.02). Several regions, in particular
CADPS gene (Ca2+-dependent secretion activator 1) region identified in MESA, were
also replicated in the ARIC cohort (Atherosclerosis Risk in Communities). We
observed other cCIMT-LEA regions associated with other clinical events, most
notably the regions harboring CKMT2 gene (creatine kinase, mitochondrial 2) and
RASGRF2 gene (Ras protein-specific guanine nucleotide-releasing factor 2) with
all clinical events except stroke, the LRRC3B gene (leucine-rich repeat
containing 3B) with myocardial infarction, the PRMT3 gene (protein arginine
methyltransferase 3) with stroke, and the LHFPL2 gene (lipoma high mobility group
protein I-C fusion partner-like 2) with hard and all coronary heart disease.
CONCLUSIONS: We identified several novel LEA regions, in addition to previously
identified genetic variations, associated with cCIMT and cardiovascular disease
events among African Americans.
PMID- 28408709
TI - Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3
Large Cohorts.
AB - BACKGROUND: Although dichotomous criteria for the metabolic syndrome (MetS)
appear heritable, it is not known whether MetS severity as assessed by a
continuous MetS score is heritable and whether this varies by race. METHODS AND
RESULTS: We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to
evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race
specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson
Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white
participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white
participants). Heritability estimates were larger for Adult Treatment Panel-III
MetS among black compared with white cohort members (JHS 0.48; 95% confidence
interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS
0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The
difference by race narrowed when assessing heritability of the MetS severity
score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15]
versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]).
There was a high degree of genetic and phenotypic correlation between MetS
severity and the individual components of MetS among all groups, although the
genetic correlations failed to reach statistical significance among PLRS blacks.
Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel
III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95%
CI, -0.05 to 0.99). CONCLUSIONS: MetS severity seems highly heritable among
whites and blacks. This continuous MetS severity Z score may provide a more
useful means of characterizing phenotypic MetS in genetic studies by minimizing
racial differences.
PMID- 28408710
TI - Local Ancestry Association, Admixture Mapping, and Ongoing Challenges.
PMID- 28408711
TI - A Randomized Controlled Trial to Determine the Appropriate Time to Initiate
Peritoneal Dialysis after Insertion of Catheter (Timely PD Study).
AB - BACKGROUND: The optimal time for the commencement of peritoneal dialysis (PD)
after PD catheter insertion is unclear. If dialysis is started too soon after
insertion, dialysate leaks and infection could occur. However, by starting PD
earlier, morbidity and costs can be reduced through lesser hemodialysis
requirements. This is the first randomized controlled trial to determine the
safest and shortest interval to commence PD after catheter insertion. METHODS:
All consecutive patients undergoing PD catheter insertion at the Royal Brisbane
and Women's Hospital and Rockhampton Hospital from 1 March 2008 to 31 May 2013
who met the inclusion and exclusion criteria were invited to participate in the
trial. Participants were randomized to 1 of 3 groups. Group 1 (G1) commenced PD
at 1 week, group 2 (G2) at 2 weeks and group 3 (G3) at 4 weeks after PD catheter
insertion. These groups were stratified by hospital and the presence of diabetes.
Primary outcomes were the incidence of peritoneal fluid leaks or PD-related
infection during the 4 weeks after commencement of PD. RESULTS: In total 122
participants were recruited, 39, 42, and 41 randomized to G1, G2, and G3,
respectively. The primary outcome catheter leak was significantly higher in G1
(28.2%) compared with G3 (2.4%, p = 0.001) but not compared with G2 (9.5%, p =
0.044), based on intention to treat analysis. These differences were even more
marked when analyzed with per protocol method: G1 had a significantly higher
percentage (32.4 %) compared with G3 (3.3%, p = 0.003) but not compared with G2
(10.5%, p = 0.040). Event percentages of leak were statistically higher in G1 and
occurred significantly earlier compared with other groups (p = 0.002). Amongst
diabetics, technique failure was significantly higher (28.6%) in G3 compared with
0% in G1 and 7.1% in G2 (p = 0.036) and earlier in G3 at 163.2 days vs 176.8 and
175.8 (p = 0.037) for G1 and G2, respectively. CONCLUSION: Leaks were higher in
participants commencing PD at 1 week after catheter insertion compared with the
other 2 groups, and technique failure was higher in diabetics starting PD at 4
weeks.
PMID- 28408712
TI - Peritoneal Dialysis Catheter Surgery using Transversus Abdominis Plane Block.
AB - BACKGROUND: Peritoneal dialysis (PD) catheter surgery can be performed using
regional anesthesia. We present our PD catheter placement and extraction
experience using ultrasound-guided transversus abdominis plane (TAP) block.
METHODS: In the present study, we analyzed 74 patients from our center with end
stage renal disease (ESRD) who underwent PD catheter placement (60 patients) and
removal (14 patients) using a TAP block between June 2011 and December 2015.
RESULTS: The TAP block was successful for 55/60 (91.7%) patients (insertion) and
13/14 (92.9%) patients (extraction). Other patients had pain at the incision site
and required general anesthesia. There were no anesthesia-, surgery- or PD
catheter-related complications. CONCLUSION: The TAP block is a safe and effective
technique not only for high-risk ESRD patients but for all patients undergoing PD
catheter placement or extraction.
PMID- 28408713
TI - The Influence of Glucose Exposure Load and Peritoneal Membrane Transport on Body
Composition and Nutritional Status Changes after 1 Year on Peritoneal Dialysis.
AB - BACKGROUND: The characteristics of peritoneal membrane transport differ among
patients, affecting the prescription of peritoneal dialysis (PD) modality and
glucose exposure in order to achieve an effective dialysis. This study aims to
verify the influence of glucose exposure load and peritoneal membrane transport
on body composition and nutritional status changes after the first year of PD.
METHODS: We examined a cohort of 85 incident PD patients during the first year of
treatment. We established a cut-off of 5% to define changes in dry weight (DW),
lean tissue mass (LTM), and fat mass (FM). RESULTS: In total, 50.6% of the
patients presented DW gain, 41.2% showed LTM loss, and 65.9% presented FM gain.
Over the time (T0 - T12), we found significant differences in DW, body mass index
(BMI), adipose tissue mass (ATM), FM and fat tissue index (FTI). Patients with
lower dialysate-to-plasma creatinine ratio showed DW and FM gain. We observed a
higher percentage of nonfast transporters in DW gain when comparing with DW no
gain. As for glucose exposure load, no body composition changes were seen.
CONCLUSIONS: Most patients presented DW gain, FM gain, and LTM loss. The
characteristics of peritoneal membrane transport affected DW during the first
year, changes being greater in nonfast than in fast transporters.
PMID- 28408714
TI - Association Between Peritoneal Glucose Exposure and Peritonitis in Peritoneal
Dialysis Patients: The balANZ Trial.
AB - BACKGROUND: Glucose is the primary osmotic medium used in most peritoneal
dialysis (PD) solutions, and exposure to glucose has been shown to exert
detrimental effects both locally, at the peritoneal membrane, and systemically.
Moreover, high dialysate glucose exposure may predispose patients to an increased
risk of peritonitis, perhaps as a result of impaired host defences, vascular
disease, and damage to the peritoneal membrane. METHODS: In this post-hoc
analysis of a multicenter, multinational, open-label randomized controlled trial
of neutral pH, low-glucose degradation product (GDP) versus conventional PD
solutions (balANZ trial), the relationship between peritonitis rates of low (<
123.1 g/day) versus high (>= 123.1 g/day) dialysate glucose exposure was
evaluated in 177 incident PD patients over a 2-year study period. RESULTS:
Peritonitis rates were 0.44 episodes per patient-year in the low-glucose exposure
group and 0.31 episodes per patient-year in the high-glucose exposure group,
(incidence rate ratio [IRR] 0.69, p = 0.09). There was no significant association
between dialysate glucose exposure and peritonitis-free survival on univariable
analysis (high glucose exposure hazard ratio [HR] 0.66, 95% confidence interval
[CI] 0.40 - 1.08) or on multivariable analysis (adjusted HR 0.64, 95% CI 0.39 -
1.05). Moreover, there was no relationship between peritoneal glucose exposure
and type of organism causing peritonitis. Physician-rated severity of first
peritonitis episodes was similar between groups, as was rate and duration of
hospital admission. CONCLUSIONS: Overall, this study did not identify an
association between peritoneal dialysate glucose exposure and peritonitis
occurrence, severity, hospitalization, or outcomes. A further large-scale,
prospective, randomized controlled trial evaluating patient-level outcomes is
merited.
PMID- 28408715
TI - Postoperative Infection in Developing World Congenital Heart Surgery Programs:
Data From the International Quality Improvement Collaborative.
AB - BACKGROUND: Postoperative infections contribute substantially to morbidity and
mortality after congenital heart disease surgery and are often preventable. We
sought to identify risk factors for postoperative infection and the impact on
outcomes after congenital heart surgery, using data from the International
Quality Improvement Collaborative for Congenital Heart Surgery in Developing
World Countries. METHODS AND RESULTS: Pediatric cardiac surgical cases performed
between 2010 and 2012 at 27 participating sites in 16 developing countries were
included. Key variables were audited during site visits. Demographics,
preoperative, procedural, surgical complexity, and outcome data were analyzed.
Univariate and multivariable logistic regression were used to identify risk
factors for infection, including bacterial sepsis and surgical site infection,
and other clinical outcomes. Standardized infection ratios were computed to track
progress over time. Of 14 545 cases, 793 (5.5%) had bacterial sepsis and 306
(2.1%) had surgical site infection. In-hospital mortality was significantly
higher among cases with infection than among those without infection (16.7%
versus 5.3%; P<0.001), as were postoperative ventilation duration (80 versus 14
hours; P<0.001) and intensive care unit stay (216 versus 68 hours; P<0.001).
Younger age at surgery, higher surgical complexity, lower oxygen saturation, and
major medical illness were independent risk factors for infection. The overall
standardized infection ratio was 0.65 (95% confidence interval, 0.58-0.73) in
2011 and 0.59 (95% confidence interval, 0.54-0.64) in 2012, compared with that in
2010. CONCLUSIONS: Postoperative infections contribute to mortality and morbidity
after congenital heart surgery. Younger, more complex patients are at particular
risk. Quality improvement targeted at infection risk may reduce morbidity and
mortality in the developing world.
PMID- 28408717
TI - Eliminating Postoperative Infections on a Budget: Collaborative Quality
Improvement for Congenital Heart Surgery in Low- and Middle-Income Countries.
PMID- 28408718
TI - Finding a Better Way.
PMID- 28408719
TI - Clinical Commentary on "Finding a Better Way".
PMID- 28408716
TI - Sex-Specific Comparative Effectiveness of Oral Anticoagulants in Elderly Patients
With Newly Diagnosed Atrial Fibrillation.
AB - BACKGROUND: Sex-specific comparative effectiveness of direct oral anticoagulants
among patients with nonvalvular atrial fibrillation is not known. Via this
retrospective cohort study, we assessed the sex-specific, comparative
effectiveness of direct oral anticoagulants (rivaroxaban and dabigatran),
compared to each other and to warfarin among patients with atrial fibrillation.
METHODS AND RESULTS: Elderly (aged >=66 years) Medicare beneficiaries enrolled in
Medicare Part D benefit plan from November 2011 to October 2013 with newly
diagnosed atrial fibrillation formed the study cohort (65 734 [44.8%] men and 81
137 [55.2%] women). Primary outcomes of inpatient admissions for ischemic strokes
and major bleeding were compared across the 3 drugs (rivaroxaban: 20 mg QD,
dabigatran: 150 mg BID, or warfarin) using 3-way propensity-matched samples. In
men, rivaroxaban use decreased stroke risk when compared with warfarin use
(hazard ratio, 0.69; 95% confidence interval, 0.48-0.99; P=0.048) and dabigatran
use (hazard ratio, 0.66; 95% confidence interval, 0.45-0.96; P=0.029) and was
associated with a similar risk of any major bleeding when compared with warfarin
and dabigatran. In women, although ischemic stroke risk was similar in the 3
anticoagulant groups, rivaroxaban use significantly increased the risk for any
major bleeding when compared with warfarin (hazard ratio, 1.20; 95% confidence
interval, 1.03-1.42; P=0.021) and dabigatran (hazard ratio, 1.27; 95% confidence
interval, 1.09-1.48; P=0.011). CONCLUSIONS: The reduced risk of ischemic stroke
in patients taking rivaroxaban, compared with dabigatran and warfarin, seems to
be limited to men, whereas the higher risk of bleeding seems to be limited to
women.
PMID- 28408720
TI - Water harvesting from air with metal-organic frameworks powered by natural
sunlight.
AB - Atmospheric water is a resource equivalent to ~10% of all fresh water in lakes on
Earth. However, an efficient process for capturing and delivering water from air,
especially at low humidity levels (down to 20%), has not been developed. We
report the design and demonstration of a device based on a porous metal-organic
framework {MOF-801, [Zr6O4(OH)4(fumarate)6]} that captures water from the
atmosphere at ambient conditions by using low-grade heat from natural sunlight at
a flux of less than 1 sun (1 kilowatt per square meter). This device is capable
of harvesting 2.8 liters of water per kilogram of MOF daily at relative humidity
levels as low as 20% and requires no additional input of energy.
PMID- 28408721
TI - Decarboxylative borylation.
AB - The widespread use of alkyl boronic acids and esters is frequently hampered by
the challenges associated with their preparation. We describe a simple and
practical method to rapidly access densely functionalized alkyl boronate esters
from abundant carboxylic substituents. This broad-scope nickel-catalyzed reaction
uses the same activating principle as amide bond formation to replace a
carboxylic acid moiety with a boronate ester. Application to peptides allowed
expedient preparations of alpha-amino boronic acids, often with high
stereoselectivity, thereby facilitating synthesis of the alkyl boronic acid drugs
Velcade and Ninlaro as well as a boronic acid version of the iconic antibiotic
vancomycin. The reaction also enabled the discovery and extensive biological
characterization of potent human neutrophil elastase inhibitors, which offer
reversible covalent binding properties.
PMID- 28408722
TI - Ephrin B1-mediated repulsion and signaling control germinal center T cell
territoriality and function.
AB - Follicular T helper (TFH) cells orchestrate the germinal center (GC) reaction
locally. Local mechanisms regulating their dynamics and helper functions are not
well defined. Here we found that GC-expressed ephrin B1 (EFNB1) repulsively
inhibited T cell to B cell adhesion and GC TFH retention by signaling through TFH
expressed EPHB6 receptor. At the same time, EFNB1 promoted interleukin-21
production from GC TFH cells by signaling predominantly through EPHB4.
Consequently, EFNB1-null GCs were associated with defective production of plasma
cells despite harboring excessive TFH cells. In a competitive GC reaction, EFNB1
deficient B cells more efficiently interacted with TFH cells and produced more
bone-marrow plasma cells, likely as a result of gaining more contact-dependent
help. Our results reveal a contact-dependent repulsive guidance system that
controls GC TFH dynamics and effector functions locally.
PMID- 28408724
TI - From protection to entitlement: selecting research subjects for early phase
clinical trials involving breakthrough therapies.
AB - Our goals are to (1) set forth and defend a multiprinciple system for selecting
individuals who meet trial eligibility criteria to participate in early phase
clinical trials testing chimeric antigen receptor (CAR T-cell) for acute
lymphoblastic leukaemia when demand for participation exceeds spaces available in
a trial; (2) show the relevance of these selection criteria to other breakthrough
experimental therapies; (3) argue that distinct distributive justice criteria
apply to breakthrough experimental therapies, standard research and healthcare
and (4) argue that as evidence of benefit increases, the emphasis of justice in
research shifts from protecting subjects from harm to ensuring fair access to
benefits.
PMID- 28408723
TI - Nucleic acid detection with CRISPR-Cas13a/C2c2.
AB - Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care
pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA
targeting clustered regularly interspaced short palindromic repeats (CRISPR)
effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of
promiscuous ribonuclease activity upon target recognition. We combine the
collateral effect of Cas13a with isothermal amplification to establish a CRISPR
based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar
sensitivity and single-base mismatch specificity. We use this Cas13a-based
molecular detection platform, termed Specific High-Sensitivity Enzymatic Reporter
UnLOCKing (SHERLOCK), to detect specific strains of Zika and Dengue virus,
distinguish pathogenic bacteria, genotype human DNA, and identify mutations in
cell-free tumor DNA. Furthermore, SHERLOCK reaction reagents can be lyophilized
for cold-chain independence and long-term storage and be readily reconstituted on
paper for field applications.
PMID- 28408725
TI - Screening for developmental delay in preschool-aged children using parent
completed Ages and Stages Questionnaires: additional insights into child
development.
AB - BACKGROUND: Developmental delay is a delay in areas of speech, language, motor,
social and cognitive development. Because of the negative impact of intellectual
and learning disabilities, early identification of children with developmental
and behavioral problems using appropriate screening tests is crucial. OBJECTIVES:
Utilization of parent-completed Ages and Stages Questionnaires (ASQs) for
detecting the developmental delay in preschool age children and clarification of
possible associated risk factors. MATERIALS AND METHODS: This cross-sectional
study was conducted on 1012 children aged 24-60 months enrolled from six centers
(n=608) and six villages (n=404) located in Menoufia Governorate, Egypt. All
children were screened by nine age-based questionnaires in the first stage of
assessment. Children whose scores were <= cut-off points in one or more of the
screened developmental areas were considered to have suspected developmental
delay (SDD) and underwent further evaluation in the second stage assessment.
RESULTS: Among the 1012 studied children aged 24-60 months, 978 (96.4%) had
normal development. SDD had an overall prevalence of 3.4%, with the highest rates
of SDD in problem-solving (3%), followed by communication (2.4%), fine motor
skills (2.2%) and social-personal domain (1%), with no SDD in gross motor skills.
SDD was more commonly observed in boys, with a significant association with both
parental education and consanguinity. Problems with learning (32.3%) was the most
commonly observed provisional diagnosis, followed by language disorders (29.4%).
Children with SDD in more than one area of ASQ skills also had mild to borderline
IQ scores. CONCLUSION: The use of of parent-completed ASQs showed an overall
prevalence of developmental delay in children aged 24-60 months of3.4%. Male
gender, consanguinity and parental education were identified as risk factors for
developmental delay. Family counselling about the child's developmental state is
needed.
PMID- 28408726
TI - Integrated surgical academic training in the UK: a cross-sectional survey.
AB - OBJECTIVES: This study aimed to explore variations in the provision of integrated
academic surgical training across the UK. DESIGN: This is an online cross
sectional survey (consisting of 44 items with a range of free-text, binomial and
5-point Likert scale responses) developed by the Association of Surgeons in
Training. SETTING: A self-reported survey instrument was distributed to academic
surgical trainees across the UK (n=276). PARTICIPANTS: 143 (51.9%) responses were
received (81% male, median age: 34 years), spanning all UK regions and surgical
specialties. Of the 143 trainees, 29 were core trainees (20.3%), 99 were
specialty trainees (69.2%) and 15 (10.5%) described themselves as research
fellows. RESULTS: The structure of academic training varied considerably, with
under a third of trainees receiving guaranteed protected time for research.
Despite this, however, 53.1% of the respondents reported to be satisfied with how
their academic training was organised. Covering clinical duties during academic
time occurred commonly (72.7%). Although most trainees (n=88, 61.5%) met with
their academic supervisor at least once a month, six (4.2%) never had an academic
supervisory meeting. Most trainees (n=90, 62.9%) occupied a full-time rota slot
and only 9.1% (n=13) described their role as 'supernumerary'. Although 58.7%
(n=84) of the trainees were satisfied with their clinical competence, 37.8%
(n=54) felt that clinical time focused more on service provision than the
acquisition of technical skills. 58 (40.6%) had experienced some form of negative
sentiment relating to their status as an academic trainee. CONCLUSIONS:
Integrated academic training presents unique challenges and opportunities within
surgery. This survey has identified variation in the quality of current
programmes, meaning that the future provision of integrated surgical academic
training should be carefully considered.
PMID- 28408727
TI - Single-nucleotide polymorphisms of the IL-12 gene lead to a higher cancer risk: a
meta-analysis based on 22,670 subjects.
AB - The associations between interleukin-12 (IL-12) gene polymorphisms and cancer
risk have been discussed extensively, with controversial results. Therefore, we
conducted the present meta-analysis to better assess the potential roles of IL-12
gene variation in cancer occurrence. Eligible articles were found via PubMed,
Medline, EMBASE, Google Scholar and CNKI. Odds ratios and 95% confidence
intervals were used to evaluate the associations between IL-12 gene polymorphisms
and cancer risk. Thirty-one studies with 10,749 cancer patients and 11,921
healthy subjects were included in the analyses. The overall results showed that
cancer risk was increased by IL-12A rs568408 (GG versus GA + AA: P = 0.004; G
versus A: P = 0.005) and IL-12B rs3212227 (AA versus AC + CC: P = 0.004; CC
versus AA + AC: P = 0.03; A versus C: P = 0.007) polymorphisms. Further subgroup
analyses for IL-12A rs568408 and IL-12B rs3212227 revealed that the positive
results could be impacted by the ethnicity of the population, cancer type and/or
genotyping methods. However, we failed to detect any significant associations
between the IL-12A rs2243115 polymorphism and cancer risk in either the overall
or the subgroup analyses. The current study suggests that certain IL-12 gene
polymorphisms serve as biological markers of cancer susceptibility.
PMID- 28408729
TI - RETRACTION.
AB - The editorial board announced this article has been retracted because of
scientific misconduct. If you have any further question, please contact us at:
kmjedit@kurume-u.ac.jp Article Title: The prevention of hip fracture with
menatetrenone and risedronate plus calcium supplementation in elderly patients
with Alzheimer disease: a randomized controlled trial Authors: Yoshihiro Sato,
Yoshiaki Honda, Kazuo Umeno, Norimasa Hayashida, Jun Iwamoto, Tsuyoshi Takeda and
Hideo Matsumoto Journal Title: Kurume Medical Journal Volume: Vol. 57, 2011
Pages: 117-124.
PMID- 28408728
TI - High Signal Intensity in Arterial Walls on Diffusion-Weighted Magnetic Resonance
Imaging in the Active Phase of Takayasu Arteritis.
PMID- 28408730
TI - ERRATA.
AB - YUKA TAKATA ET AL. KURUME MEDICAL JOURNAL, 60, 89-97, 2013 The name of the third
author on page 89, the author index and the back cover should be "TAISUKE KANAJI"
and not "TAISUKE KANAJII".
PMID- 28408731
TI - Long-Term Outcome After Liver Transplantation for Hepatocellular Carcinoma
Following Yttrium-90 Radioembolization Bridging Treatment.
AB - BACKGROUND Bridging treatments are employed in liver transplant waitlist patients
with hepatocellular carcinoma (HCC) because of the risk of tumor progression
during the waiting time. Radioembolization is mostly employed in the control of
large or multifocal HCCs when other locoregional treatment modalities cannot be
applied because of the number or size of lesions. The purpose of this study was
to evaluate our experience with the use of radioembolization as a bridge to
transplantation and its effect on tumor recurrence and survival after liver
transplantation. MATERIAL AND METHODS A retrospective review of 40 consecutive
patients with HCC who underwent liver transplantation after radioembolization
bridging treatment between January 2007 and December 2015 at the University
Hospital Essen, Germany, was performed. Patients' characteristics, alpha
fetoprotein (AFP) levels, pathologic tumor response, tumor recurrence rate, and
survival rates were examined through chart review. RESULTS Histopathological
examination of the explanted liver specimen revealed complete tumor necrosis in
17 specimens, partial necrosis in 18 specimens, and no significant necrosis in
five specimens. Median overall survival was 46 months. Nine patients developed
recurrent HCC. Median time from liver transplantation to diagnosis of tumor
recurrence was 15 months. There was a trend towards a lower risk of tumor
recurrence for patients with complete necrosis on explant specimens. Patients
with tumor recurrence demonstrated statistically significantly higher pre- and
post-treatment AFP levels (p=0.0234 and p=0.0236) and statistically significantly
more frequently microvascular invasion (p=0.0163). CONCLUSIONS Histopathological
assessment of explanted livers revealed at least partial necrosis in 87.5% of
patients. Patients with successful bridging treatment, i.e. complete necrosis of
explant specimens, demonstrate a trend towards a lower risk of tumor recurrence.
PMID- 28408732
TI - Glial Cell Line-Derived Neurotrophic Factor-Transfected Placenta-Derived Versus
Bone Marrow-Derived Mesenchymal Cells for Treating Spinal Cord Injury.
AB - BACKGROUND Placenta-derived mesenchymal stem cells (PMSCs) were isolated from
placenta and had differentiation and self-renewal potential. We transfected PMSCs
with glial cell line-derived neurotrophic factor (GDNF) and compared their effect
for repairing spinal cord injury (SCI) with that of GDNF-transfected bone marrow
derived mesenchymal stem cell (BMSC). MATERIAL AND METHODS The PMSCs were
isolated from Sprague-Dawley rat placenta; BMSCs were isolated from Sprague
Dawley rat thigh bone marrow. Primary cultured BMSCs and PMSCs were uniformly
spindle-shaped. Flow cytometry indicated that both cell types were CD29- and CD90
positive and CD34- and CD45-negative, confirming that they were MSCs. The PMSCs
and BMSCs were transfected with recombinant lentivirus containing the GDNF gene
in vitro. PMSC and BMSC viability was increased after transfection, and GDNF
expression was increased until 10 d after transfection. SCI was created in the
rats (n=64) and was repaired using transfected PMSCs and BMSCs or untransfected
PMSCs and BMSCs. RESULTS The transfected PMSCs and BMSCs repaired the SCI. Flow
cytometry, histology, immunohistochemical, kinesiology properties, and Basso
Beattie-Bresnahan locomotion score measurements determined no significant
difference between transfected PMSCs and BMSCs at 7, 14, and 21 d post
transplantation (P>0.05); the injury healed better in transfected PMSCs and BMSCs
than in untransfected PMSCs and BMSCs (P<0.05). CONCLUSIONS MSCs have similar
biology characteristics and capacity for SCI repair to BMSCs and can be used as a
new resource for treating SCI.
PMID- 28408733
TI - High-Performance Liquid Chromatography (HPLC) Quantification of Liposome
Delivered Doxorubicin in Arthritic Joints of Collagen-Induced Arthritis Rats.
AB - BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early
rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that
allows nanoparticle agents, including liposomes, to deliver encapsulated drugs to
arthritic joints and subsequently improve therapeutic efficacy and reduce adverse
effects. However, the targeting distribution of liposomes in arthritic joints
during RA has not been quantitatively demonstrated. We performed this study to
evaluate the targeting distribution of PEGylated doxorubicin liposomes in the
arthritic joints of collagen-induced arthritis (CIA) rats by high-performance
liquid chromatography (HPLC). MATERIAL AND METHODS Two doxorubicin formulations
were administered to CIA rats via tail intravenous injection at a single dose (50
mg/m2). CIA rats were sacrificed and the tissues of the inflamed ankle joints
were collected. The content of doxorubicin in the arthritic joints was analyzed
by a validated and reproducible HPLC method. A two-way ANOVA for 2*5 factorial
design was used for statistical analysis. RESULTS The developed HPLC method was
sensitive, precise, and reproducible. The method was successfully applied to
quantify doxorubicin content in arthritic tissues. At each time point (6, 12, 24,
48, and 72 h), doxorubicin content in the arthritic joints of the doxorubicin
liposome group (DOX-LIP group) was higher than in the free doxorubicin group (DOX
group) (P<0.05). In the DOX-LIP group, doxorubicin levels in the arthritic joints
increased gradually and significantly in the interval of 6-72 h post
administration. CONCLUSIONS PEGylated doxorubicin liposomes were targeted to,
accumulated, and retained in the arthritic joints of CIA rats. The present study
indicates that liposome encapsulation increases the therapeutic efficacy of
antirheumatic drugs, presenting a promising therapeutic strategy for RA.
PMID- 28408734
TI - Mycophenolate Mofetil and Pulmonary Fibrosis After Kidney Transplantation: A Case
Report.
AB - BACKGROUND Mycophenolate mofetil (MMF) induced lung disease has been described in
only a few isolated reports. We report a case of fatal respiratory failure
associated with MMF after kidney transplantation. CASE REPORT A 50-year-old
Hispanic male with a history of end-stage renal disease secondary to hypertension
underwent deceased donor kidney transplantation. His preoperative evaluations
were normal except for a chest x-ray which showed bilateral interstitial
opacities. Tacrolimus and MMF were started on the day of surgery. His
postoperative course was uneventful and he was discharged on postoperative day 5.
One month later, he presented with shortness of breath and a cough with blood
tinged sputum. His respiratory condition deteriorated rapidly, requiring
intubation. Chest computer tomography (CT) demonstrated patchy ground-glass
opacities with interlobular septal thickening. Comprehensive pulmonary, cardiac,
infectious, and immunological evaluations were all negative. Open lung biopsy
revealed extensive pulmonary fibrosis with no evidence of infection. He
temporarily improved after discontinuation of tacrolimus and MMF, however, on
resuming MMF his respiratory status deteriorated again and he subsequently died
from hypoxic respiratory failure. CONCLUSIONS An awareness of pulmonary lung
disease due to MMF is important to prevent adverse outcomes after organ
transplantation. MMF must be used with utmost care in recipients with underlying
lung disease as their pulmonary condition might make them more susceptible to any
harmful effects of MMF.
PMID- 28408735
TI - Predicting neurological Adverse Drug Reactions based on biological, chemical and
phenotypic properties of drugs using machine learning models.
AB - Adverse drug reactions (ADRs) have become one of the primary reasons for the
failure of drugs and a leading cause of deaths. Owing to the severe effects of
ADRs, there is an urgent need for the generation of effective models which can
accurately predict ADRs during early stages of drug development based on
integration of various features of drugs. In the current study, we have focused
on neurological ADRs and have used various properties of drugs that include
biological properties (targets, transporters and enzymes), chemical properties
(substructure fingerprints), phenotypic properties (side effects (SE) and
therapeutic indications) and a combinations of the two and three levels of
features. We employed relief-based feature selection technique to identify
relevant properties and used machine learning approach to generated learned model
systems which would predict neurological ADRs prior to preclinical testing.
Additionally, in order to explain the efficiency and applicability of the models,
we tested them to predict the ADRs for already existing anti-Alzheimer drugs and
uncharacterized drugs, respectively in side effect resource (SIDER) database. The
generated models were highly accurate and our results showed that the models
based on chemical (accuracy 93.20%), phenotypic (accuracy 92.41%) and combination
of three properties (accuracy 94.18%) were highly accurate while the models based
on biological properties (accuracy 82.11%) were highly informative.
PMID- 28408736
TI - MIEF1/2 function as adaptors to recruit Drp1 to mitochondria and regulate the
association of Drp1 with Mff.
AB - Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1
to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2
(MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in
mammals. However, if and how these receptors work together in mitochondrial
fission is poorly understood. Here we show that MIEFs interact with both Drp1 and
Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff
together in a trimeric Drp1-MIEF-Mff complex. Thus, MIEFs can regulate the
interaction between Drp1 and Mff, and also Mff-induced Drp1 accumulation on
mitochondria. It is shown that loss of endogenous MIEFs severely impairs these
processes. Additionally, in cells depleted of endogenous MIEF1/2, high levels of
exogenous MIEFs sequester Drp1 on the mitochondrial surface, resulting in
mitochondrial elongation, whereas low-to-moderate levels of MIEFs promote
mitochondrial fission, leading to mitochondrial fragmentation. In sum, the data
suggest that MIEFs and Mff work coordinately in Drp1-mediated mitochondrial
fission and that the level of MIEF1/2 relative to Mff sets the balance between
mitochondrial fission and fusion.
PMID- 28408737
TI - Hydrogen sulfide toxicity inhibits primary root growth through the ROS-NO
pathway.
AB - High concentrations of hydrogen sulfide (H2S) are toxic to plants and inhibit
their growth. Previous research indicated that high concentrations of H2S
modulate the root system architecture (RSA) by affecting auxin transport;
however, the signaling pathway underlying this process remains unclear. Here, we
investigated the effects of exogenous sodium hydrosulfide (NaHS), an H2S donor,
on primary root (PR) growth in Arabidopsis using pharmacological, physiological,
and genetic approaches. H2S toxicity repressed PR growth by triggering a signal
transduction pathway involving reactive oxygen species (ROS) accumulation,
MITOGEN-ACTIVATED PROTEIN KINASE 6 (MPK6) activation, and nitric oxide (NO)
production. Respiratory burst oxidase homolog mutants and an NO synthase mutant
were less sensitive to NaHS, suggesting that both ROS and NO mediate the
inhibitory effects of H2S on PR growth. We found that exogenous H2S-activated ROS
production was required for NO generation and that MPK6 mediated H2S-induced NO
production. MPK6 was shown to function downstream of ROS and upstream of NO.
Finally, we demonstrated that exogenous H2S repressed the distribution of auxin
and reduced the meristematic cell division potential in root tips, and NO was
involved in this process.
PMID- 28408738
TI - Identification of exosomes and its signature miRNAs of male and female
Cynoglossus semilaevis.
AB - Exosomes are small membrane particles which are widely found in various cell
lines and physiological fluids in mammalian. MicroRNAs (miRNAs) enclosed in
exosomes have been identified as proper signatures for many diseases and response
to therapies. However, the composition of exosomes and enclosed miRNAs in fishes
has not been investigated. Cynoglossus semilaevis is an important commercial
flatfish with ambiguous distinction between males and females before sex
maturation, which leads to screening difficulty in reproduction and cultivation.
An effective detection method was required for sex differentiation of C.
semilaevis. In this work, we successfully identified exosomes in C. semilaevis
serum. The analysis of nucleotide composition showed that miRNA dominated in
exosomes. Thereafter the miRNA profiles in exosomes from males and females were
sequenced and compared to identify the signature miRNAs corresponding to sex
differentiation. The functions of signature miRNAs were analyzed by target
matching and annotation. Furthermore, 7 miRNAs with high expression in males were
selected from signature miRNAs as the markers for sex identification with their
expression profiles verified by real time quantitative PCR. Exosomes were first
found in fish serum in this work. Investigation of marker miRNAs supplies an
effective index for the filtration of male and female C. semilaevis in
cultivation.
PMID- 28408739
TI - Strongly bound excitons in anatase TiO2 single crystals and nanoparticles.
AB - Anatase TiO2 is among the most studied materials for light-energy conversion
applications, but the nature of its fundamental charge excitations is still
unknown. Yet it is crucial to establish whether light absorption creates
uncorrelated electron-hole pairs or bound excitons and, in the latter case, to
determine their character. Here, by combining steady-state angle-resolved
photoemission spectroscopy and spectroscopic ellipsometry with state-of-the-art
ab initio calculations, we demonstrate that the direct optical gap of single
crystals is dominated by a strongly bound exciton rising over the continuum of
indirect interband transitions. This exciton possesses an intermediate character
between the Wannier-Mott and Frenkel regimes and displays a peculiar two
dimensional wavefunction in the three-dimensional lattice. The nature of the
higher-energy excitations is also identified. The universal validity of our
results is confirmed up to room temperature by observing the same elementary
excitations in defect-rich samples (doped single crystals and nanoparticles) via
ultrafast two-dimensional deep-ultraviolet spectroscopy.Here the authors combine
steady-state angle-resolved photoemission spectroscopy, ellipsometry and
ultrafast two-dimensional ultraviolet spectroscopy to examine the role of many
body correlations in anatase TiO2, revealing the existence of strongly bound
excitons in single crystals and nanoparticles.
PMID- 28408740
TI - Multi-component quantitative magnetic resonance imaging by phasor representation.
AB - Quantitative magnetic resonance imaging (qMRI) is a versatile, non-destructive
and non-invasive tool in life, material, and medical sciences. When multiple
components contribute to the signal in a single pixel, however, it is difficult
to quantify their individual contributions and characteristic parameters. Here we
introduce the concept of phasor representation to qMRI to disentangle the signals
from multiple components in imaging data. Plotting the phasors allowed for
decomposition, unmixing, segmentation and quantification of our in vivo data from
a plant stem, a human and mouse brain and a human prostate. In human brain
images, we could identify 3 main T 2 components and 3 apparent diffusion
coefficients; in human prostate 5 main contributing spectral shapes were
distinguished. The presented phasor analysis is model-free, fast and accurate.
Moreover, we also show that it works for undersampled data.
PMID- 28408741
TI - Establishment of a novel human lymphoblastic cell strain with the long arm of
chromosome 11 aberration without MLL rearrangement.
AB - At present, all cell strains derived from acute lymphoblastic leukemia (ALL)
patients with the long arm of chromosome 11 aberration are accompanied with mixed
lineage leukemia (MLL) gene rearrangement. In this study, we established a
permanent ALL cell strain CHH-1 with the long arm of chromosome 11 aberration and
without MLL rearrangement, hoping that it could be used for the research of ALL
with such genetic abnormality. CHH-1 cell strain was certified through
morphology, immunophenotype, genetics and immunoglobulin (Ig) gene rearrangement
analysis. Cell characteristics including tumorigenic ability, semisolid colony
forming ability, telomerase activity, autocrine and invasion were further
detected. Cells were with an add(11)(q23) structural abnormality without MLL
rearrangement, and were consistent with the genetic abnormality of the patient.
In addition, these cells had features of tumor-forming ability, high colony
forming capacity, unique cytokine autocrine mode, high telomerase activity, and
high invasion ability. CHH-1 may prove to be a useful cell model for the research
of human leukemia with genetic aberration in chromosome 11, and help explore the
role of such genetic abnormality in the pathogenesis, progression and prognosis
of ALL, and in developing new target drugs.
PMID- 28408742
TI - Effectiveness and success factors of educational inhaler technique interventions
in asthma & COPD patients: a systematic review.
AB - With the current wealth of new inhalers available and insurance policy driven
inhaler switching, the need for insights in optimal education on inhaler use is
more evident than ever. We aimed to systematically review educational inhalation
technique interventions, to assess their overall effectiveness, and identify main
drivers of success. Medline, Embase and CINAHL databases were searched for
randomised controlled trials on educational inhalation technique interventions.
Inclusion eligibility, quality appraisal (Cochrane's risk of bias tool) and data
extraction were performed by two independent reviewers. Regression analyses were
performed to identify characteristics contributing to inhaler technique
improvement. Thirty-seven of the 39 interventions included (95%) indicated
statistically significant improvement of inhaler technique. However, average
follow-up time was relatively short (5 months), 28% lacked clinical relevant
endpoints and all lacked cost-effectiveness estimates. Poor initial technique,
number of inhalation procedure steps, setting (outpatient clinics performing
best), and time elapsed since intervention (all, p < 0.05), were shown to have an
impact on effectiveness of the intervention, explaining up to 91% of the
effectiveness variation. Other factors, such as disease (asthma vs. chronic
obstructive pulmonary disease), education group size (individual vs. group
training) and inhaler type (dry powder inhalers vs. pressurised metered dose
inhalers) did not play a significant role. Notably, there was a trend (p = 0.06)
towards interventions in adults being more effective than those in children and
the intervention effect seemed to wane over time. In conclusion, educational
interventions to improve inhaler technique are effective on the short-term.
Periodical intervention reinforcement and longer follow-up studies, including
clinical relevant endpoints and cost-effectiveness, are recommended.
PMID- 28408743
TI - Pestalotiopsis and allied genera from Camellia, with description of 11 new
species from China.
AB - A total of 124 Pestalotiopsis-like isolates associated with symptomatic and
asymptomatic tissues of Camellia sinensis and other Camellia spp. from eight
provinces in China were investigated. Based on single- and multi-locus (ITS, TEF,
TUB2) phylogenies, as well as morphological characters, host associations and
geographical distributions, they were classified into at least 19 species in
three genera, i.e. Neopestalotiopsis, Pestalotiopsis and Pseudopestalotiopsis.
Eight novel species in Pestalotiopsis and three novel species in
Pseudopestalotiopsis were described. Our data suggested that the currently widely
used loci in Pestalotiopsis-like genera do not consistently provide stable and
sufficient resolution tree topologies, especially for Neopestalotiopsis.
Moreover, the number, branch pattern and length of the conidial basal appendages
were revealed to be phylogenetically informative characters in Pestalotiopsis.
PMID- 28408744
TI - Room-temperature field effect transistors with metallic ultrathin TiN-based
channel prepared by atomic layer delta doping and deposition.
AB - Metallic channel transistors have been proposed as the candidate for sub-10 nm
technology node. However, the conductivity modulation in metallic channels can
only be observed at low temperatures usually below 100 K. In this study, room
temperature field effect and modulation of the channel resistance was achieved in
the metallic channel transistors, in which the oxygen-doped TiN ultrathin-body
channels were prepared by the atomic layer delta doping and deposition (AL3D)
with precise control of the channel thickness and electron concentration. The
decrease of channel thickness leads to the reduction in electron concentration
and the blue shift of absorption spectrum, which can be explained by the onset of
quantum confinement effect. The increase of oxygen incorporation results in the
increase of interband gap energy, also giving rise to the decrease in electron
concentration and the blue shift of absorption spectrum. Because of the
significant decrease in electron concentration, the screening effect was greatly
suppressed in the metallic channel. Therefore, the channel modulation by the gate
electric field was achieved at room temperature due to the quantum confinement
and suppressed screening effect with the thickness down to 4.8 nm and the oxygen
content up to 35% in the oxygen-doped TiN ultrathin-body channel.
PMID- 28408745
TI - SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive
dendritic morphogenesis.
AB - Forkhead Box P (FOXP) transcriptional repressors play a major role in brain
development and their dysfunction leads to human cognitive disorders. However,
little is known about how the activity of these proteins is regulated. Here, we
show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co
repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly
controlled by neuronal activity, in which synapse to nucleus signalling, mediated
via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation.
Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and
this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1
K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of
proper neuronal morphogenesis. These results suggest that activity-dependent
SUMOylation of FOXP1 may be an important mediator of early cortical development
and neuronal network formation in the brain.
PMID- 28408747
TI - Alice-Bob Physics: Coherent Solutions of Nonlocal KdV Systems.
AB - In natural and social science, many events happened at different space-times may
be closely correlated. Two events, A (Alice) and B (Bob) are defined correlated
if one event is determined by another, say, [Formula: see text] for suitable
[Formula: see text] operators. Taking KdV and coupled KdV systems as examples, we
can find some types of models (AB-KdV systems) to exhibit the existence on the
correlated solutions linked with two events. The idea of this report is valid not
only for physical problems related to KdV systems but also for problems described
by arbitrary continuous or discrete models. The parity and time reversal
symmetries are extended to shifted parity and delayed time reversal. The new
symmetries are found to be useful not only to establish AB-systems but also to
find group invariant solutions of numerous AB-systems. A new elegant form of the
N-soliton solutions of the KdV equation and then the AB-KdV systems is obtained.
A concrete AB-KdV system derived from the nonlinear inviscid dissipative and
barotropic vorticity equation in a beta-plane channel is applied to the two
correlated monople blocking events which is responsible for the snow disaster in
the winter of 2007/2008 happened in Southern China.
PMID- 28408746
TI - Novel metrics to measure coverage in whole exome sequencing datasets reveal local
and global non-uniformity.
AB - Whole Exome Sequencing (WES) is a powerful clinical diagnostic tool for
discovering the genetic basis of many diseases. A major shortcoming of WES is
uneven coverage of sequence reads over the exome targets contributing to many low
coverage regions, which hinders accurate variant calling. In this study, we
devised two novel metrics, Cohort Coverage Sparseness (CCS) and Unevenness (UE)
Scores for a detailed assessment of the distribution of coverage of sequence
reads. Employing these metrics we revealed non-uniformity of coverage and low
coverage regions in the WES data generated by three different platforms. This non
uniformity of coverage is both local (coverage of a given exon across different
platforms) and global (coverage of all exons across the genome in the given
platform). The low coverage regions encompassing functionally important genes
were often associated with high GC content, repeat elements and segmental
duplications. While a majority of the problems associated with WES are due to the
limitations of the capture methods, further refinements in WES technologies have
the potential to enhance its clinical applications.
PMID- 28408748
TI - The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy
smokers and COPD patients.
AB - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease,
and bacterial infection plays a role in its pathogenesis. Bacteria secrete
nanometer-sized extracellular vesicles (EVs), which may induce more immune
dysfunction and inflammation than the bacteria themselves. We hypothesized that
the microbiome of lung EVs might have distinct characteristics depending on the
presence of COPD and smoking status. We analyzed and compared the microbiomes of
13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy
smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of
surgical lung tissue and lung EVs. Subjects were matched for age and sex in all
groups and for smoking levels in the COPD and healthy smoker groups. Each group
included 12 men and 1 woman with the same mean age of 65.5 years. In all groups,
EVs consistently showed more operational taxonomic units (OTUs) than lung tissue.
In the healthy smoker and COPD groups, EVs had a higher Shannon index and a lower
Simpson index than lung tissue and this trend was more prominent in the COPD
group. Principal component analysis (PCA) showed clusters based on sample type
rather than participants' clinical characteristics. Stenotrophomonas,
Propionibacterium and Alicyclobacillus were the most commonly found genera.
Firmicutes were highly present in the EVs of the COPD group compared with other
samples or groups. Our analysis of the lung microbiome revealed that the
bacterial communities present in the EVs and in the COPD group possessed distinct
characteristics with differences in the OTUs, diversity indexes and PCA
clustering.
PMID- 28408750
TI - Transcriptional regulatory networks underlying the reprogramming of
spermatogonial stem cells to multipotent stem cells.
AB - Spermatogonial stem cells (SSCs) are germline stem cells located along the
basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to
be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and
biological networks underlying this reprogramming remain elusive. Here, we
present transcriptional regulatory networks (TRNs) that control cellular
processes related to the SSC-to-mSSC reprogramming. Previously, we established
intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene
expression profiles of SSCs, iSSCs and mSSCs. By comparing these profiles, we
identified 2643 genes that were up-regulated during the reprogramming process and
15 key transcription factors (TFs) that regulate these genes. Using the TF-target
relationships, we developed TRNs describing how these TFs regulate three
pluripotency-related processes (cell proliferation, stem cell maintenance and
epigenetic regulation) during the reprogramming. The TRNs showed that 4 of the 15
TFs (Oct4/Pou5f1, Cux1, Zfp143 and E2f4) regulated cell proliferation during the
early stages of reprogramming, whereas 11 TFs (Oct4/Pou5f1, Foxm1, Cux1, Zfp143,
Trp53, E2f4, Esrrb, Nfyb, Nanog, Sox2 and Klf4) regulated the three pluripotency
related processes during the late stages of reprogramming. Our TRNs provide a
model for the temporally coordinated transcriptional regulation of pluripotency
related processes during the SSC-to-mSSC reprogramming, which can be further
tested in detailed functional studies.
PMID- 28408749
TI - High prevalence of TP53 mutations is associated with poor survival and an EMT
signature in gliosarcoma patients.
AB - Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical
genomic challenges because of its poor prognosis and limited genomic information.
To gain a comprehensive view of the genomic alterations in GS and to understand
the molecular etiology of GS, we applied whole-exome sequencing analyses for 28
GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin
fixed paraffin-embedded tissues for the validation set) and copy-number variation
microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more
prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%),
and the GS patients with TP53 mutations showed a significantly shorter survival
(multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87
199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK
signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling
(CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3)
pathways. Genomic profiling of the matched recurrent GS cases detected the
occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53
mutations play a role in treatment resistance. Functionally, we found that TP53
mutations are associated with the epithelial-mesenchymal transition (EMT) process
of sarcomatous components of GS. We provide the first comprehensive genome-wide
genetic alternation profiling of GS, which suggests novel prognostic subgroups in
GS patients based on their TP53 mutation status and provides new insight in the
pathogenesis and targeted treatment of GS.
PMID- 28408751
TI - MMP9 integrates multiple immunoregulatory pathways that discriminate high
suppressive activity of human mesenchymal stem cells.
AB - The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are
largely unknown. We here show that highly suppressive human adipose tissue
derived MSC (AdMSC) display and induce a differential immunologic profile, upon
ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of
IFN-gamma and TNF-alpha production, along IL-10 increase, (ii) CD73+Foxp3+Treg
subset expansion, and (iii) specific correlations between gene expression
increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in
AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21,
among others, whereas MMP2 correlated with BCL2 and LRRC31. MMP9 emerged as an
integrating molecule for both AdMSC and T cells in molecular networks built with
our gene expression data, and we confirmed upregulation of MMP9 and MMP2 at the
protein level, in AdMSC and T cells, respectively. MMP2/9 inhibition
significantly decreased AdMSC suppressive effect, confirming their important role
in suppressive acitivity. We conclude that MMP9 and 2 are robust new players
involved in human MSC immunoregulatory mechanisms, and the higher suppressive
activity correlates to their capacity to trigger a coordinated action of multiple
specific molecules, mobilizing various immunoregulatory mechanisms.
PMID- 28408752
TI - High resolution neutron Larmor diffraction using superconducting magnetic
Wollaston prisms.
AB - The neutron Larmor diffraction technique has been implemented using
superconducting magnetic Wollaston prisms in both single-arm and double-arm
configurations. Successful measurements of the coefficient of thermal expansion
of a single-crystal copper sample demonstrates that the method works as expected.
The experiment involves a new method of tuning by varying the magnetic field
configurations in the device and the tuning results agree well with previous
measurements. The difference between single-arm and double-arm configurations has
been investigated experimentally. We conclude that this measurement benchmarks
the applications of magnetic Wollaston prisms in Larmor diffraction and shows in
principle that the setup can be used for inelastic phonon line-width
measurements. The achievable resolution for Larmor diffraction is comparable to
that using Neutron Resonance Spin Echo (NRSE) coils. The use of superconducting
materials in the prisms allows high neutron polarization and transmission
efficiency to be achieved.
PMID- 28408753
TI - A combined experimental and first-principle study on the oxidation mechanism of
super austenitic stainless steel S32654 at 900 degrees C.
AB - A combined experimental and first-principle study on the oxidation mechanism of
super austenitic stainless steel S32654 at 900 degrees C for a short time period
(1, 3, and 5 h) in air is presented. The samples exhibit excellent oxidation
resistance because of the initial and gradual formation of the denser Fe- and Cr
rich layer with increasing oxidation time. Meanwhile, the Mo-rich layer gradually
forms because of the Mo diffusion, which results in the formation of the oxide
layer with two distinct regions: an inner Fe- and Cr-rich layer and an outer Mo
rich layer. Density functional theory is applied to investigate the diffusion
behaviour of Mo atom in the Fe-Cr-Ni/Cr2O3 interface and the effects of alloying
elements (Fe, Ni, and Mn) on the Mo diffusion. The Mo originating from the alloy
matrix tends to diffuse into the Cr2O3 part, thereby resulting in the formation
of the continuous Mo-rich layer, which is consistent with the experimental
behaviour. Moreover, the introduction of Ni to the Cr2O3 part can promote the Mo
diffusion and the formation of the Mo-rich oxide layer, whereas Fe and Mn can
hinder the Mo diffusion. The calculated results provide a microcosmic explanation
of the experimental results.
PMID- 28408754
TI - Lack of association of C3 gene with uveitis: additional insights into the genetic
profile of uveitis regarding complement pathway genes.
AB - Uveitis is a devastating ocular disease that causes blindness. Our previous
studies have achieved great advancements in depicting the genetic profiles of
uveitis regarding complement pathway genes. This study aimed to provide
additional insights into this interest by testing the "central" factor of the
complement system, C3 gene variants, in two uveitis entities. Eight haplotype
tagging SNPs of C3 gene were genotyped in 141 anterior uveitis (AU), 158 non
infectious intermediate and posterior uveitis (NIPU) and 293 controls. The
results showed that none of the tagging SNPs had a significant association with
uveitis (P > 0.05), either in the global uveitis or subtypes. Although rs428453
showed a nominal association with NIPU subtype in the recessive model (P =
0.042), the P value could not withstand the Bonferroni correction (P corr >
0.05). Stratification analyses according to HLA-B27 status and correlation
analysis still did not find any significant interactions or genetic markers
regarding AU. Logistic regression analysis also revealed no gender-related
epistatic effects of C3 on uveitis. Two haplotype blocks were defined across the
C3 locus but neither of them was significantly associated with uveitis or
subtypes. This study shows no significant association of the C3 gene with
uveitis, suggesting C3 confers either no or limited risk for uveitis
susceptibility.
PMID- 28408755
TI - Light Induced Electron-Phonon Scattering Mediated Resistive Switching in
Nanostructured Nb Thin Film Superconductor.
AB - The elemental Nb is mainly investigated for its eminent superconducting
properties. In contrary, we report of a relatively unexplored property, namely,
its superior optoelectronic property in reduced dimension. We demonstrate here
that nanostructured Nb thin films (NNFs), under optical illumination, behave as
room temperature photo-switches and exhibit bolometric features below its
superconducting critical temperature. Both photo-switch and superconducting
bolometric behavior are monitored by its resistance change with light in visible
and near infrared (NIR) wavelength range. Unlike the conventional photodetectors,
the NNF devices switch to higher resistive states with light and the
corresponding resistivity change is studied with thickness and grain size
variations. At low temperature in its superconducting state, the light exposure
shifts the superconducting transition towards lower temperature. The room
temperature photon sensing nature of the NNF is explained by the photon assisted
electron-phonon scattering mechanism while the low temperature light response is
mainly related to the heat generation which essentially changes the effective
temperature for the device and the device is capable of sensing a temperature
difference of few tens of milli-kelvins. The observed photo-response on the
transport properties of NNFs can be very important for future superconducting
photon detectors, bolometers and phase slip based device applications.
PMID- 28408757
TI - Defect-Induced Luminescence Quenching vs. Charge Carrier Generation of Phosphorus
Incorporated in Silicon Nanocrystals as Function of Size.
AB - Phosphorus doping of silicon nanostructures is a non-trivial task due to problems
with confinement, self-purification and statistics of small numbers. Although P
atoms incorporated in Si nanostructures influence their optical and electrical
properties, the existence of free majority carriers, as required to control
electronic properties, is controversial. Here, we correlate structural, optical
and electrical results of size-controlled, P-incorporating Si nanocrystals with
simulation data to address the role of interstitial and substitutional P-atoms.
Whereas atom probe tomography proves that P-incorporation scales with nanocrystal
size, luminescence spectra indicate that even nanocrystals with several P-atoms
still emit light. Current-voltage measurements demonstrate that majority carriers
must be generated by field emission to overcome the P-ionization energies of 110
260 meV. In absence of electrical fields at room temperature, no significant free
carrier densities are present, which disproves the concept of luminescence
quenching via Auger recombination. Instead, we propose non-radiative
recombination via interstitial-P induced states as quenching mechanism. Since
only substitutional-P provides occupied states near the Si conduction band, we
use the electrically measured carrier density to derive formation energies of
~400 meV for P-atoms on Si nanocrystal lattice sites. Based on these results we
conclude that ultrasmall Si nanovolumes cannot be efficiently P-doped.
PMID- 28408756
TI - Apple pomace improves the quality of pig manure aerobic compost by reducing
emissions of NH3 and N2O.
AB - In this study, the effects of apple pomace (AP) addition (0%, 5%, 10%, and 20% on
a dry weight basis, named as control, AP1, AP2, and AP3) and citric acid (CA)
addition on nitrogen conservation were investigated during aerobic composting of
pig manure. Gaseous emissions of NH3 and N2O were inhibited by AP and CA
addition, with AP's effect greater. The inhibition improved with increasing AP
addition. The AP3 treatment was the most effective on NH3 adsorption and
transformation to [Formula: see text]-N, improved with subsequent transformation
to [Formula: see text]-N, and inhibition of N2O and [Formula: see text]
production. Compared with control, AP3 showed the highest inhibition of
accumulated NH3 and N2O emission, by 57% and 24%, respectively, and with a 19%
increase of total Kjeldahl nitrogen in the compost. The further pot experiment
proved the application of the AP amendment compost could improve the yield and
trace element nutrient accumulation in Chinese cabbage when planted in a typical
Zn-deficient soil. This study illustrates that AP application benefits both
compost nitrogen conservation and fertilizer quality.
PMID- 28408758
TI - Super-tunable, broadband up-conversion of a high-power CW laser in an engineered
nonlinear crystal.
AB - A specially-designed chirped periodically poled lithium niobate nonlinear crystal
was fabricated with a phase-matching bandwidth as large as 50 nm for sum
frequency generation to operate at room and higher temperatures. This device also
benefits from insensitivity to laser frequency drift and fine alignment. The
loosely-focused beam position of a high-power CW laser at around 1550 nm is
optimized within the grating for maximum up-conversion efficiency, to realize a
super-tunable source in the range of 770-778 nm by tuning a narrowband control
signal over 30 nm in the communication band. This device is demonstrated to be
fully phased-matched simultaneously for both second-order nonlinear up-conversion
processes, namely second harmonic generation and sum frequency generation. The
measurement of the generated sum-frequency power versus wavelength agrees well
with the theory. The device allows for the creation of tunable broadband CW
sources at shorter wavelengths with potentially high power.
PMID- 28408759
TI - Reliably estimating prevalences of atopic children: an epidemiological study in
an extensive and representative primary care database.
AB - : Electronic health records stored in primary care databases might be a valuable
source to study the epidemiology of atopic disorders and their impact on health
care systems and costs. However, the prevalence of atopic disorders in such
databases varies considerably and needs to be addressed. For this study, all
children aged 0-18 years listed in a representative primary care database in the
period 2002-2014, with sufficient data quality, were selected. The effects of
four different strategies on the prevalences of atopic disorders were examined:
(1) the first strategy examined the diagnosis as recorded in the electronic
health records, whereas the (2) second used additional requirements (i.e., the
patient had at least two relevant consultations and at least two relevant
prescriptions). Strategies (3) and (4) assumed the atopic disorders to be chronic
based on strategy 1 and 2, respectively. When interested in cases with a higher
probability of a clinically relevant disorder, strategy 2 yields a realistic
estimation of the prevalence of atopic disorders derived from primary care data.
Using this strategy, of the 478,076 included children, 28,946 (6.1%) had eczema,
29,182 (6.1%) had asthma, and 28,064 (5.9%) had allergic rhinitis; only 1251
(0.3%) children had all three atopic disorders. Prevalence rates are highly
dependent on the clinical atopic definitions used. The strategy using cases with
a higher probability of clinically relevant cases, yields realistic prevalences
to establish the impact of atopic disorders on health-care systems. However,
studies are needed to solve the problem of identifying atopic disorders that are
missed or misclassified. ATOPIC DISORDERS: CLINICAL INFORMATION IMPROVES
PREVALENCE ESTIMATES: The prevalence of atopic disorders in children can be more
reliably calculated by incorporating clinical information with diagnosis data.
Researchers in the Netherlands, led by David Pols from the Erasmus University
Medical Center Rotterdam, examined the electronic health records of more than
660,000 children, aged 0 to 18, from a Dutch primary care database to determine
the number of cases of atopic eczema, asthma, and allergic rhinitis. They looked
for diagnosed children who also had at least two relevant clinical consultations
and at least two relevant prescriptions. This strategy helps correct for the
problem of overestimation, because it doesnot assume that a child, once
diagnosed, will have an atopic disorder for life. However, other methods are
still needed to identify cases that are missed or misclassified in the health
database.
PMID- 28408760
TI - Fungal volatile compounds induce production of the secondary metabolite Sodorifen
in Serratia plymuthica PRI-2C.
AB - The ability of bacteria and fungi to communicate with each other is a remarkable
aspect of the microbial world. It is recognized that volatile organic compounds
(VOCs) act as communication signals, however the molecular responses by bacteria
to fungal VOCs remain unknown. Here we perform transcriptomics and proteomics
analyses of Serratia plymuthica PRI-2C exposed to VOCs emitted by the fungal
pathogen Fusarium culmorum. We find that the bacterium responds to fungal VOCs
with changes in gene and protein expression related to motility, signal
transduction, energy metabolism, cell envelope biogenesis, and secondary
metabolite production. Metabolomic analysis of the bacterium exposed to the
fungal VOCs, gene cluster comparison, and heterologous co-expression of a terpene
synthase and a methyltransferase revealed the production of the unusual terpene
sodorifen in response to fungal VOCs. These results strongly suggest that VOCs
are not only a metabolic waste but important compounds in the long-distance
communication between fungi and bacteria.
PMID- 28408761
TI - Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into
Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair.
AB - Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial
cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral
Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach
for ALS. This study aimed to determine effects of transplanted unmodified human
bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal
cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received
one of three different doses of hBM34+ cells. Cell-treated, media-treated, and
control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human
vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed
in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma
determined capillary permeability. Transplanted hBM34+ cells improved behavioral
disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose
mice. Transplanted cells differentiated into ECs and engrafted within numerous
capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end
feet astrocytes were also determined in spinal cords, mostly in high-cell-dose
mice. These mice also showed significantly decreased parenchymal EB levels. EC
differentiation, capillary engraftment, reduced capillary permeability, and re
established perivascular end-feet astrocytes in symptomatic ALS mice may
represent BSCB repair processes, supporting hBM34+ cell transplantation as a
future therapeutic strategy for ALS patients.
PMID- 28408762
TI - Interplay of buried histidine protonation and protein stability in prion
misfolding.
AB - Misofolding of mammalian prion proteins (PrP) is believed to be the cause of a
group of rare and fatal neurodegenerative diseases. Despite intense scrutiny
however, the mechanism of the misfolding reaction remains unclear. We perform
nuclear Magnetic Resonance and thermodynamic stability measurements on the C
terminal domains (residues 90-231) of two PrP variants exhibiting different pH
induced susceptibilities to aggregation: the susceptible hamster prion (GHaPrP)
and its less susceptible rabbit homolog (RaPrP). The pKa of histidines in these
domains are determined from titration experiments, and proton-exchange rates are
measured at pH 5 and pH 7. A single buried highly conserved histidine, H187/H186
in GHaPrP/RaPrP, exhibited a markedly down shifted pKa ~5 for both proteins.
However, noticeably larger pH-induced shifts in exchange rates occur for GHaPrP
versus RaPrP. Analysis of the data indicates that protonation of the buried
histidine destabilizes both PrP variants, but produces a more drastic effect in
the less stable GHaPrP. This interpretation is supported by urea denaturation
experiments performed on both PrP variants at neutral and low pH, and correlates
with the difference in disease susceptibility of the two species, as expected
from the documented linkage between destabilization of the folded state and
formation of misfolded and aggregated species.
PMID- 28408763
TI - Silicon Solar Cells on Glass with Power Conversion Efficiency above 13% at
Thickness below 15 Micrometer.
AB - Liquid phase crystallized silicon on glass with a thickness of (10-40) MUm has
the potential to reduce material costs and the environmental impact of
crystalline silicon solar cells. Recently, wafer quality open circuit voltages of
over 650 mV and remarkable photocurrent densities of over 30 mA/cm2 have been
demonstrated on this material, however, a low fill factor was limiting the
performance. In this work we present our latest cell progress on 13 MUm thin poly
crystalline silicon fabricated by the liquid phase crystallization directly on
glass. The contact system uses passivated back-side silicon hetero-junctions,
back-side KOH texture for light-trapping and interdigitated ITO/Ag contacts. The
fill factors are up to 74% and efficiencies are 13.2% under AM1.5 g for two
different doping densities of 1 . 1017/cm3 and 2 . 1016/cm3. The former is
limited by bulk and interface recombination, leading to a reduced saturation
current density, the latter by series resistance causing a lower fill factor.
Both are additionally limited by electrical shading and losses at grain
boundaries and dislocations. A small 1 * 0.1 cm2 test structure circumvents
limitations of the contact design reaching an efficiency of 15.9% clearly showing
the potential of the technology.
PMID- 28408764
TI - Fossil climbing perch and associated plant megafossils indicate a warm and wet
central Tibet during the late Oligocene.
AB - Understanding the Tibetan Plateau's palaeogeography and palaeoenvironment is
critical for reconstructing Asia's climatic history; however, aspects of the
plateau's uplift history remain unclear. Here, we report a fossil biota that
sheds new light on these issues. It comprises a fossil climbing perch
(Anabantidae) and a diverse subtropical fossil flora from the Chattian (late
Oligocene) of central Tibet. The fish, Eoanabas thibetana gen. et sp. nov., is
inferred to be closely related to extant climbing perches from tropical lowlands
in south Asia and sub-Saharan Africa. It has osteological correlates of a
labyrinth organ, which in extant climbing perches gives them the ability to
breathe air to survive warm, oxygen-poor stagnant waters or overland excursion
under moist condition. This indicates that Eoanabas likewise lived in a warm and
humid environment as suggested by the co-existing plant assemblage including
palms and golden rain trees among others. As a palaeoaltimeter, this fossil biota
suggests an elevation of ca. 1,000 m. These inferences conflict with conclusions
of a high and dry Tibet claimed by some recent and influential palaeoaltimetry
studies. Our discovery prompts critical re-evaluation of prevailing uplift models
of the plateau and their temporal relationships with the Cenozoic climatic
changes.
PMID- 28408765
TI - Active Mediation of Plasmon Enhanced Localized Exciton Generation, Carrier
Diffusion and Enhanced Photon Emission.
AB - Understanding the enhancement of charge carrier generation and their diffusion is
imperative for improving the efficiency of optoelectronic devices particularly
infrared photodetectors that are less developed than their visible counterpart.
Here, using gold nanorods as model plasmonic systems, InAs quantum dots (QDs)
embedded in an InGaAs quantum well as an emitter, and GaAs as an active mediator
of surface plasmons for enhancing carrier generation and photon emission, the
distance dependence of energy transfer and carrier diffusion have been
investigated both experimentally and theoretically. Analysis of the QD emission
enhancement as a function of distance reveals a Forster radius of 3.85 +/- 0.15
nm, a near-field decay length of 4.8 +/- 0.1 nm and an effective carrier
diffusion length of 64.0 +/- 3.0 nm. Theoretical study of the temporal-evolution
of the electron-hole occupation number of the excited states of the QDs indicates
that the emission enhancement trend is determined by the carrier diffusion and
capture rates.
PMID- 28408766
TI - Family (Dis)Advantage and Life Course Expectations.
AB - Optimistic assessments of life chances can positively influence life outcomes,
but conflicting theories suggest these assessments either reflect structural
privilege or develop as a result of childhood hardship. In addition, competing
hypotheses suggest that these assessments may matter differently depending on who
holds them. We examine whether family socioeconomic status shapes adolescents'
expectations about how successful their lives will turn out. We distinguish
generalized life expectations (GLE), capturing anticipated success in life across
multiple domains, from intergenerational comparative expectations (ICE), which
register expectations about improvement relative to observed success within the
respondent's family lineage. We find that adolescents from higher socioeconomic
status families are simultaneously more optimistic about their likely success in
life (GLE) but less likely to anticipate relative improvement in life success
across generations (ICE). Holding high GLE in combination with low ICE predicted
doing better in adulthood across a range of health, attainment, and well-being
outcomes, though in most cases high GLE, regardless of ICE, was the key. These
beneficial patterns are, for the most part, at least as beneficial for
socioeconomically disadvantaged youth as they are for advantaged youth.
PMID- 28408767
TI - Prevalence and Correlates of Physical Dating Violence among North American
Indigenous Adolescents.
AB - This study examined the lifetime prevalence of physical dating violence,
including victimization, perpetration, and the overlap between the two (mutual
violence) among a population sample of 551 reservation/reserve residing
Indigenous (i.e., American Indian and Canadian First Nations) adolescents in the
upper-Midwest of the United States and Canada. Potential correlates of four
dating violence profiles (i.e., no dating violence, perpetration-only,
victimization-only, and mutual violence) relevant to this population also were
considered. The clearest pattern to emerge from multinomial logistic regression
analyses suggested that adolescents who engage in problem behaviors, exhibit high
levels of anger, and perceive high levels of discrimination have increased odds
of lifetime mutual dating violence relative to those reporting no dating
violence. Furthermore, gender comparisons indicated that females were more likely
to report being perpetrators only, while males were more likely to report being
victims only. Considerations of dating violence profiles and culturally-relevant
prevention strategies are discussed.
PMID- 28408768
TI - Substance Use and Depression in Home Visiting Clients: Home Visitor Perspectives
on Addressing Clients' Needs.
AB - Substance use and depression are prevalent among mothers enrolled in home
visiting programs and are significant risk factors for child maltreatment, yet
most home visiting programs are staffed by workers who lack the training and
clinical skills to address these risks. Emanating from one state network's
interest in advancing its practice in this area, the current study surveyed 159
home visitors on their current practices, training, knowledge, and perceived self
efficacy, and perceived system- and client-level barriers regarding client
substance use and depression. Home visitors reported managing maternal depression
more extensively than substance use, though overall management of both risk areas
was low. More training was associated with more extensive management of both risk
domains, as was greater home visitor knowledge and self-efficacy. Implications
for the development of strategies to improve home visitor management of client
behavioral health risks, including enhanced skills-based training and
supervision, are discussed.
PMID- 28408769
TI - Variable- and Person-Centered Approaches to Examining Temperament Vulnerability
and Resilience to the Effects of Contextual Risk.
AB - Using both variable- and person-centered approaches, this study examined the role
of temperament in relation to children's vulnerable or resilient responses to
cumulative risk. Observed reactivity and regulation dimensions of temperament
were tested as mediating and moderating the relation between family cumulative
risk and teacher-reported adjustment problems in a sample of 259 preschool-age
children. Further, latent profile analyses were used to examine whether profiles
of temperament, accounting for multiple characteristics simultaneously, provided
additional information about the role of temperament in children's responses to
risk. Results support a diathesis-stress model in which high frustration, low
fear, and low delay ability confer particular vulnerability for children in high
risk contexts. Benefits of multiple approaches are highlighted.
PMID- 28408770
TI - Personality in the Age of Industry: Structure, Heritability, and Correlates of
Personality in Middle Childhood from the Perspective of Parents, Teachers, and
Children.
AB - Middle childhood is a crucial juncture in the lifespan where children work
towards achieving a sense of competence foundational for future development.
However, middle childhood has historically been underrepresented in the
personality literature. The current study provides a comprehensive examination of
personality in middle childhood using a large (N = 2510), longitudinal sample of
10- to 12-year-old twins. The structure, heritability, and correlates of
personality in this period were investigated using personality ratings of
parents, teachers, and children. Results showed that personality in middle
childhood has a coherent structure, is heritable, and is relevant for
developmentally salient outcomes such as externalizing behavior, substance use,
and academic engagement. Results emphasize the importance of investigating
personality in middle childhood across multiple informants.
PMID- 28408771
TI - Was Venus the First Habitable World of our Solar System?
AB - Present-day Venus is an inhospitable place with surface temperatures approaching
750K and an atmosphere 90 times as thick as Earth's. Billions of years ago the
picture may have been very different. We have created a suite of 3-D climate
simulations using topographic data from the Magellan mission, solar spectral
irradiance estimates for 2.9 and 0.715 Gya, present-day Venus orbital parameters,
an ocean volume consistent with current theory, and an atmospheric composition
estimated for early Venus. Using these parameters we find that such a world could
have had moderate temperatures if Venus had a rotation period slower than ~16
Earth days, despite an incident solar flux 46-70% higher than Earth receives. At
its current rotation period, Venus's climate could have remained habitable until
at least 715 million years ago. These results demonstrate the role rotation and
topography play in understanding the climatic history of Venus-like exoplanets
discovered in the present epoch.
PMID- 28408772
TI - Issues raised by a case of orbital metastatic disease.
AB - The clinical, radiological and histopathological findings in an 81-year-old man
presenting with lung carcinoma metastatic to the orbit are described. Orbital
biopsy was complicated by postoperative visual loss and failed to contribute
significantly to the final diagnosis. The authors believe that in cases of
possible orbital metastases a primary neoplasm should be excluded by means of a
complete oncological assessment before proceeding to biopsy.
PMID- 28408774
TI - Historical Analyses of Disordered Handwriting: Perspectives on Early 20th-Century
Material From a German Psychiatric Hospital.
AB - Handwritten texts carry significant information, extending beyond the meaning of
their words. Modern neurology, for example, benefits from the interpretation of
the graphic features of writing and drawing for the diagnosis and monitoring of
diseases and disorders. This article examines how handwriting analysis can be
used, and has been used historically, as a methodological tool for the assessment
of medical conditions and how this enhances our understanding of historical
contexts of writing. We analyze handwritten material, writing tests and letters,
from patients in an early 20th-century psychiatric hospital in southern Germany
(Irsee/Kaufbeuren). In this institution, early psychiatrists assessed handwriting
features, providing us novel insights into the earliest practices of psychiatric
handwriting analysis, which can be connected to Berkenkotter's research on
medical admission records. We finally consider the degree to which historical
handwriting bears semiotic potential to explain the psychological state and
personality of a writer, and how future research in written communication should
approach these sources.
PMID- 28408773
TI - Can Mitochondria DNA Provide a Novel Biomarker for Evaluating the Risk and
Prognosis of Colorectal Cancer?
AB - Colorectal cancer (CRC) was one of the most frequent cancers worldwide. Accurate
risk and prognosis evaluation could obtain better quality of life and longer
survival time for the patients. Current research hotspot was focus on the gene
biomarker to evaluate the risk and prognosis. Mitochondrion contains its own DNA
and regulates self-replicating so that it can be as a candidate biomarker for
evaluating the risk and prognosis of colorectal cancer. But there were already
huge controversies on this issue. The review was to summarize current viewpoints
of the controversial issues and described our understanding from the four aspects
including mtDNA copy number, mitochondrial displacement loop, mtDNA variation,
and mtDNA microsatellite instability, wishing the summary of the mtDNA in
colorectal cancer could provide a meaningful reference or a valuable direction in
the future studies.
PMID- 28408775
TI - Detection of genome, antigen, and antibodies in oral fluids from pigs infected
with foot-and-mouth disease virus.
AB - Virus nucleic acids and antibody response to pathogens can be measured using
swine oral fluids (OFs). Detection of foot-and-mouth disease virus (FMDV) genome
in swine OFs has previously been demonstrated. Virus isolation and viral antigen
detection are additional confirmatory assays for diagnosing FMDV, but these
methods have not been evaluated using swine OF. The objectives of this study were
to further validate the molecular detection of FMDV in oral fluids, evaluate
antigen detection and FMDV isolation from swine OFs, and develop an assay for
isotypic anti-FMDV antibody detection in OFs. Ribonucleic acid (RNA) from FMDV
was detected in OFs from experimentally infected pigs by quantitative real-time
reverse transcription polymerase chain reaction (qRT-PCR) from 1 day post
infection (dpi) to 21 dpi. Foot-and-mouth disease virus (FMDV) was isolated from
OFs at 1 to 5 dpi. Additionally, FMDV antigens were detected in OFs from 1 to 6
dpi using a lateral flow immunochromatographic strip test (LFIST), which is a
rapid pen-side test, and from 2 to 3 dpi using a double-antibody sandwich enzyme
linked immunosorbent assay (DAS ELISA). Furthermore, FMDV-specific immunoglobulin
A (IgA) was detected in OFs using an isotype-specific indirect ELISA starting at
dpi 14. These results further demonstrated the potential use of oral fluids for
detecting FMDV genome, live virus, and viral antigens, as well as for quantifying
mucosal IgA antibody response.
PMID- 28408776
TI - Application of direct polymerase chain reaction assays for Campylobacter fetus
subsp. venerealis and Tritrichomonas foetus to screen preputial samples from
breeding bulls in cow-calf herds in western Canada.
AB - The primary objectives of this study were to estimate the prevalence of
Campylobacter fetus subsp. venerealis (Cfv) and Tritrichomonas foetus in breeding
bulls from a sentinel cohort of cow-calf herds in western Canada and to estimate
the association between positive test status and non-pregnancy. The final
objective was to evaluate the application of these tests when: i) screening bulls
in the absence of a recognized problem with reproductive performance, and ii)
testing for diagnosis of poor pregnancy rates. The crude apparent bull prevalence
for Cfv was 1.1% [95% confidence interval (CI): 0.5% to 2.1%; 8/735] and herd
prevalence was 2.6% (95% CI: 0.3% to 9.0%; 2/78). The crude apparent bull
prevalence for T. foetus was < 0.001% (95% CI: 0.0% to 0.5%; 0/735) and herd
prevalence was < 0.001% (95% CI: 0.0% to 4.6%; 0/78). Cows from herds where at
least 1 bull was test positive for Cfv were 2.35 times more likely (95% CI: 1.01%
to 5.48%; P = 0.047) to not be pregnant than those with no positive bulls.
Polymerase chain reaction (PCR) testing of preputial material collected into
phosphate-buffered saline (PBS) was recommended for screening for T. foetus when
the pre-test probability of infection was > 1%. The same test for Cfv was not
recommended for screening moderate- and low-risk herds due to the high risk of
false positives. Tests for both T. foetus and Cfv can be used to investigate
herds with reproductive problems when also ruling out other risk factors.
Regardless of the type of test used, however, 3 negative tests are required to
rule out infection in high-risk situations.
PMID- 28408777
TI - Efficacy of an accelerated hydrogen peroxide disinfectant to inactivate porcine
epidemic diarrhea virus in swine feces on metal surfaces.
AB - In May of 2013, porcine epidemic diarrhea virus (PEDV) was detected in swine for
the first time in North America. It spread rapidly, in part due to contaminated
livestock trailers. The objective of this study was to test the efficacy of an
accelerated hydrogen peroxide disinfectant for inactivating PEDV in the presence
of feces on metal surfaces, such as those found in livestock trailers. Three-week
old barrows were inoculated intragastrically with 5 mL of PEDV-negative feces for
the negative control, 5 mL of untreated PEDV-positive feces for the positive
control, and 5 mL or 10 mL of PEDV-positive feces that was subjected to treatment
with a 1:16 or 1:32 concentrations of accelerated hydrogen peroxide disinfectant
for a contact time of 30 min at 20 degrees C. These pigs served as a bioassay to
determine the infectivity of virus following treatment. Rectal swabs collected
from the inoculated pigs on days 3 and 7 post-inoculation were tested by using
PEDV-specific real-time reverse transcription polymerase chain reaction and the
proportion of pigs in each group that became infected with PEDV was assessed.
None of the pigs used for the bioassay in the 4 treatment groups and the negative
control group became infected with PEDV, which was significantly different from
the positive control group (P < 0.05) in which all pigs were infected. The
results suggest that the application of the accelerated hydrogen peroxide under
these conditions was sufficient to inactivate the virus in feces found on metal
surfaces.
PMID- 28408778
TI - Concurrent vaccination of boars with type 1 and type 2 porcine reproductive and
respiratory syndrome virus (PRRSV) reduces seminal shedding of type 1 and type 2
PRRSV.
AB - The objective of the present study was to determine the effect of concurrent
vaccination of boars with type 1 and type 2 porcine reproductive and respiratory
syndrome virus (PRRSV) on seminal shedding of both genotypes. The boars tolerated
well concurrent administration of 2 commercial PRRSV vaccines, and no adverse
reactions were observed. No interference in the humoral immune response (measured
as the level of anti-PRRSV antibodies) or the cell-mediated immune response
(measured as the level of PRRSV-specific interferon-gamma-secreting cells) was
observed after concurrent administration compared with single administration of
the same vaccines. Concurrent vaccination significantly reduced the load of type
1 and type 2 PRRSV in blood and semen after singular (type 1 or type 2) and dual
(type 1 and type 2) PRRSV challenge, and it did not significantly affect the
efficacy of each vaccine. The results demonstrate that concurrent vaccination of
boars with type 1 and type 2 PRRSV reduces shedding of both genotypes in semen.
PMID- 28408779
TI - Effect of the probiotic Lactobacillus murinus LbP2 on clinical parameters of dogs
with distemper-associated diarrhea.
AB - The objective of this study was to assess the effect of the probiotic
Lactobacillus murinus native strain (LbP2) on general clinical parameters of dogs
with distemper-associated diarrhea. Two groups of dogs over 60 d of age with
distemper and diarrhea were used in the study, which was done at the Animal
Hospital of the Veterinary Faculty of the University of Uruguay, Montevideo,
Uruguay. The dogs were treated orally each day for 5 d with the probiotic or with
a placebo (vehicle without bacteria). Clinical parameters were assessed and
scored according to a system specially designed for this study. Blood parameters
were also measured. Administration of the probiotic significantly improved the
clinical score of the patients, whereas administration of the placebo did not.
Stool output, fecal consistency, mental status, and appetite all improved in the
probiotic-treated dogs. These results support previous findings of beneficial
effects with the probiotic L. murinus LbP2 in dogs. Thus, combined with other
therapeutic measures, probiotic treatment appears to be promising for the
management of canine distemper-associated diarrhea.
PMID- 28408780
TI - Lactobacillus casei regulates differentiation of Th17/Treg cells to reduce
intestinal inflammation in mice.
AB - In order to study the ability of Lactobacillus casei to ameliorate murine
enteritis, 18 mice were randomly divided into 3 groups: the enteritis group,
intervention group, and control group. The interleukin (IL)-6 and transforming
growth factor-beta (TGF)-beta content in mouse peripheral blood and duodenum was
detected using an enzyme-linked immunosorbent assay (ELISA). The number of
CD4+CD25+Foxp3+ T-regulatory cells (Tregs) and CD4+IL-17A+ Th17 cells in the
mesenteric lymph nodes (MLN) and spleen were detected using flow cytometry, and
quantitative reverse transcription polymerase chain reaction (PCR) and western
blot analysis were used to measure Foxp3 and retinoid-related orphan receptor
gamma (RORgammat) mRNA and protein expression in the MLN. Histological changes in
the duodenum were observed. Results indicate that in the intervention group, IL-6
content in mouse peripheral blood and duodenum was significantly lower than in
the enteritis group (P < 0.05), while TGF-beta content was significantly
increased compared to the enteritis group (P < 0.05). For the intervention group,
the percentages of CD4+CD25+Foxp3+ Tregs in spleen and MLN were increased (P <
0.05), while the percentages of CD4+IL-17A+ Th17 cells were decreased compared to
the enteritis group (P < 0.05). The expression of Foxp3 mRNA and protein in the
intervention group was higher than in the enteritis group, while RORgammat mRNA
and protein were significantly lower (P < 0.05). After mice in the enteritis
group were treated with L. casei, duodenal inflammation was relieved. This study
demonstrated that L. casei could have possible implications for the
enterotoxigenic Escherichia coli (ETEC) induced intestinal inflammation by
regulating the ratio imbalance of Th17/Treg cells.
PMID- 28408781
TI - Inflammatory bowel disease affects density of nitrergic nerve fibers in the
mucosal layer of the canine gastrointestinal tract.
AB - The objective of this study was to determine the effect of inflammatory bowel
disease (IBD) on the density of nitrergic nerve fibers in the mucosal layer of
different sections of the gastrointestinal tract of dogs. Twenty-eight German
shepherd hybrid dogs of both sexes, weighing from 15 to 25 kg and aged 6 to 10 y,
were studied. The dogs were divided into 4 groups with 7 animals in each group:
healthy animals, as well as dogs suffering from mild, moderate, and severe IBD.
Immunoreactivity to neuronal isoform of nitric oxide synthase, which is a marker
of nitrergic neurons, in samples of the mucosal layer in the duodenum, jejunum,
and descending colon was studied using the single immunofluorescence method and
the number of nerve fibers was evaluated in each observation field. The obtained
results showed that IBD causes an increase in the number of nitrergic nerve
fibers in all intestinal segments studied and these changes are directly
proportional to the intensity of the disease process. These observations may be
useful in diagnostic evaluation of the stage of canine inflammatory bowel disease
in veterinary practice. The pathological mechanisms of these observed changes and
the specific reasons for them are still not completely explained, however, and
further study is required.
PMID- 28408782
TI - Assessment of regional left ventricular systolic function by strain imaging
echocardiography in phenotypically normal and abnormal Maine coon cats tested for
the A31P mutation in the MYBPC3 gene.
AB - Myocardial dysfunction occurs in cats with hypertrophic cardiomyopathy (HCM), but
little is known about the early stages of the disease. Strain imaging
echocardiography is a method that enables the quantitative assessment of
myocardial function and deformity, allowing the characterization of systolic
dysfunction. The objective of this study was to assess systolic function using
strain imaging echocardiography in Maine coon cats genetically tested for the
A31P mutation in the MYBPC3 gene, with and without ventricular hypertrophy. For
this purpose, 57 Maine coon cats of both genders, with an unknown status
regarding the mutation at inclusion, were included prospectively and evaluated by
conventional and strain imaging echocardiography. Comparisons were made among
cats without hypertrophy (n = 45), suspect cats (n = 7), and cats with
hypertrophic cardiomyopathy (n = 5), and also between the heterozygous for the
mutation group (n = 26) and the negative for the mutation group (n = 28).
Finally, in the group of phenotypically normal cats, heterozygous cats carrying
the mutation were compared to cats without the mutation. Strain values were
compared among the groups (blinded prospective study). While echocardiography
demonstrated normal contractility, strain values (middle of the septum) were
lower in HCM cats. Strain values (base of anterior wall of the left ventricle)
were lower in heterozygous than in negative cats, even before hypertrophy.
Negative correlation was observed between some values of myocardial strain and
thickness. While strain imaging echocardiography was able to detect systolic
abnormalities, despite apparent normality on conventional echocardiography, it
was not able to identify cats that carry the A31P mutation in the MYBPC3 gene.
Strain imaging echocardiography could be a useful tool, however, for detecting
systolic alterations in HCM cats with an apparently normal systolic function or
for detecting alterations in normal carriers of the MYBPC3 gene mutation.
PMID- 28408783
TI - Prokaryotic expression of the extracellular domain of porcine programmed death 1
(PD-1) and its ligand PD-L1 and identification of the binding with peripheral
blood mononuclear cells in vitro.
AB - Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28
family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the
expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs.
Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD
L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the
present study the extracellular domains of PD-1 and PD-L1 were used to evaluate
the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs). We
amplified the cDNA encoding the extracellular domains of PD-1 and PD-L1 to
construct recombinant expression plasmids and obtain soluble recombinant
proteins, which were then labeled with fluorescein isothiocyanate (FITC). The His
ExPD-1 and His-ExPD-L1 recombinant proteins were expressed in the form of
inclusion bodies with a relative molecular weight of 33.0 and 45.0 kDa,
respectively. We then prepared polyclonal antibodies against the proteins with a
multi-antiserum titer of 1:102 400. Binding of the proteins with PBMCs was
evaluated by flow cytometry. The fluorescence signals of His-ExPD-1-FITC and His
ExPD-L1-FITC were greater than those for the FITC control. These results suggest
that the soluble recombinant proteins may be used to prepare monoclonal
antibodies to block the PD-1/PD-L1 pathway.
PMID- 28408784
TI - Prevalence of small ruminant lentivirus and Mycobacterium avium subsp.
paratuberculosis co-infection in Ontario dairy sheep and dairy goats.
AB - Infection with small ruminant lentiviruses (SRLV) causes a variety of chronic
inflammatory conditions that limit production. Mycobacterium avium subsp.
paratuberculosis (MAP) is also a major production-limiting disease of sheep and
goats, which causes severe inflammation of the small intestine. Previous studies
have indicated that both SRLV and MAP are widespread in small ruminants in
Ontario. This study estimated the prevalence of SRLV and MAP co-infection. Serum
samples that were previously tested for MAP infection were re-tested for SRLV.
The apparent prevalence of co-infection was low, with 3.4% [95% confidence
interval (CI): 1.9 to 5.9] and 14.3% (95% CI: 11.6 to 17.5) of sheep and goats
respectively, positive for both infections. However, co-infection is widespread
with 36.8% (95% CI: 19.1 to 59.1) and 71.4% (95% CI: 52.8 to 84.9) of sheep and
goat farms with 1 or more co-infected animals. A significant association was
found between SRLV seropositivity and MAP fecal culture (P = 0.021), suggesting
that co-infected goats may be more likely to shed MAP in their feces.
PMID- 28408785
TI - All anxiety is not created equal: Correlates of parent/youth agreement vary
across subtypes of anxiety.
AB - Research has examined patterns and correlates of parent/youth informant
discrepancies in the reporting of youth anxiety. However, little work has
examined whether it is better to conceptualize patterns and correlates of
informant disagreement across anxiety broadly, or more useful to consider
disagreement on specific symptom clusters. Using data from the Child
Adolescent/Anxiety Multimodal Study (CAMS; N = 488; Walkup et al., 2008), the
current study applied the most recent recommended analytic strategies to study
informant discrepancies and examined differences in the magnitude and patterns of
disagreement for: (a) broadband anxiety symptoms, versus (b) symptoms of specific
anxiety diagnoses (or anxiety subtypes; e.g., separation, social anxiety).
Correlates of informant discrepancies were also examined. Results indicated that
there was variability in agreement across anxiety subtypes, with parent/youth
agreement higher on separation anxiety and school refusal symptoms relative to
other domains. Parental psychopathology was associated with disagreement on
broadband anxiety symptoms, such that parental psychopathology was highest when
parents reported higher symptoms than their children; however, this finding was
largely driven by a relationship between parental psychopathology and
disagreement on separation anxiety symptoms. Age was associated with disagreement
on total and separation anxiety symptoms. Gender was not associated with
disagreement. Clinical implications are discussed.
PMID- 28408786
TI - On Critical Behaviour in Systems of Hamiltonian Partial Differential Equations.
AB - We study the critical behaviour of solutions to weakly dispersive Hamiltonian
systems considered as perturbations of elliptic and hyperbolic systems of
hydrodynamic type with two components. We argue that near the critical point of
gradient catastrophe of the dispersionless system, the solutions to a suitable
initial value problem for the perturbed equations are approximately described by
particular solutions to the Painleve-I (P[Formula: see text]) equation or its
fourth-order analogue P[Formula: see text]. As concrete examples, we discuss
nonlinear Schrodinger equations in the semiclassical limit. A numerical study of
these cases provides strong evidence in support of the conjecture.
PMID- 28408787
TI - Isotropy of Angular Frequencies and Weak Chimeras with Broken Symmetry.
AB - The notion of a weak chimeras provides a tractable definition for chimera states
in networks of finitely many phase oscillators. Here, we generalize the
definition of a weak chimera to a more general class of equivariant dynamical
systems by characterizing solutions in terms of the isotropy of their angular
frequency vector-for coupled phase oscillators the angular frequency vector is
given by the average of the vector field along a trajectory. Symmetries of
solutions automatically imply angular frequency synchronization. We show that the
presence of such symmetries is not necessary by giving a result for the existence
of weak chimeras without instantaneous or setwise symmetries for coupled phase
oscillators. Moreover, we construct a coupling function that gives rise to
chaotic weak chimeras without symmetry in weakly coupled populations of phase
oscillators with generalized coupling.
PMID- 28408788
TI - Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency
following DBS.
AB - Objective. Reduced verbal fluency is a strikingly uniform finding following deep
brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive
mechanism underlying this reduction remains unclear, but theories have suggested
reduced motivation, linguistic skill, and/or executive function. It is of note,
however, that previous reports have failed to consider the potential role of any
changes in speed of processing. Thus, the aim of this study was to examine verbal
fluency changes with a particular focus on the role of cognitive speed. Method.
In this study, 28 patients with PD completed measures of verbal fluency,
motivation, language, executive functioning, and speed of processing, before and
after DBS. Results. As expected, there was a marked decline in verbal fluency but
also in a timed test of executive functions and two measures of speed of
processing. Verbal fluency decline was associated with markers of linguistic and
executive functioning, but not after speed of processing was statistically
controlled for. In contrast, greater decline in verbal fluency was associated
with higher levels of apathy at baseline, which was not associated with changes
in cognitive speed. Discussion. Reduced generativity and processing speed may
account for the marked reduction in verbal fluency commonly observed following
DBS.
PMID- 28408789
TI - Social Victimization Trajectories From Middle Childhood Through Late Adolescence.
AB - Social victimization refers to being targeted by behaviors intended to harm one's
social status or relationships (Underwood, 2003), including malicious gossip,
friendship manipulation, and social exclusion (both verbal and non-verbal). The
current study examined social victimization experiences longitudinally from
middle childhood through late adolescence. Participants (N = 273, 139 females)
reported on their social victimization experiences in grades 4-11 (ages 9 to 16
years). Using mixture (group-based) modeling, four social victimization
trajectories were identified: low, medium decreasing, medium increasing, and
elevated. High parent-child relationship quality decreased the odds of being in
the elevated group compared to the low group; however, parent-child relationship
quality was no longer a significant predictor when emotional dysfunction was
added to the model. Higher emotional dysfunction and male gender increased the
odds of being in the elevated group and medium increaser group relative to the
low group even after controlling for parent-child relationship quality.
Implications for intervention and future research directions are discussed.
PMID- 28408790
TI - HBV Viral Load and Liver Enzyme Levels May Be Associated with the Wild MBL2 AA
Genotype.
AB - The present study investigated the frequencies of rs1800450 (MBL *B, G>A),
rs1800451 (MBL *C, G>A), and rs5030737 (MBL *D, C>T) polymorphisms in exon 1 of
the MBL2 gene among patients with chronic viral hepatitis. Blood samples from
patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n
= 92), and a noninfected control group (n = 300) were investigated. The presence
of polymorphisms was detected using a real-time polymerase chain reaction to
correlate with liver disease pathogenesis and fibrosis staging according to the
Metavir classification. The genotypic and allelic frequencies showed no
significant differences between the groups, but patients with active HBV and the
wild AA genotype presented a positive correlation between increased transaminase
and HBV DNA levels and the presence of mild to moderate fibrosis. Patients with
HCV and the wild AA genotype presented mild inflammation and higher HCV RNA
levels, although the same association was not observed for the fibrosis scores.
The results suggest that the mutations in exon 1 of the MBL2 gene do not
contribute directly to the clinical and laboratory features of HCV and HBV
infections, but further studies should be performed to confirm whether the wild
AA genotype has indirect effect on disease progression.
PMID- 28408792
TI - Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and
Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma.
AB - Ionizing radiation combined with trauma tissue injury (combined injury, CI)
results in greater mortality and H-ARS than radiation alone (radiation injury,
RI), which includes thrombocytopenia. The aim of this study was to determine
whether increases in numbers of thrombocytes would improve survival and mitigate
H-ARS after CI. We observed in mice that WBC and platelets remained very low in
surviving RI animals that were given 9.5 Gy 60Co-gamma-photon radiation, whereas
only lymphocytes and basophils remained low in surviving CI mice that were
irradiated and then given skin wounds. Numbers of RBC and platelets, hemoglobin
concentrations, and hematocrit values remained low in surviving RI and CI mice.
CI induced 30-day mortality higher than RI. Radiation delayed wound healing by
approximately 14 days. Treatment with a thrombopoietin receptor agonist,
Alxn4100TPO, after CI improved survival, mitigated body-weight loss, and reduced
water consumption. Though this therapy delayed wound-healing rate more than in
vehicle groups, it greatly increased numbers of platelets in sham, wounded, RI,
and CI mice; it significantly mitigated decreases in WBC, spleen weights, and
splenocytes in CI mice and decreases in RBC, hemoglobin, hematocrit values, and
splenocytes and splenomegaly in RI mice. The results suggest that Alxn4100TPO is
effective in mitigating CI.
PMID- 28408793
TI - Optimal linear estimation under unknown nonlinear transform.
AB - Linear regression studies the problem of estimating a model parameter beta* ?R p
, from n observations [Formula: see text] from linear model yi = +
epsilon i . We consider a significant generalization in which the relationship
between and yi is noisy, quantized to a single bit, potentially
nonlinear, noninvertible, as well as unknown. This model is known as the single
index model in statistics, and, among other things, it represents a significant
generalization of one-bit compressed sensing. We propose a novel spectral-based
estimation procedure and show that we can recover beta* in settings (i.e.,
classes of link function f) where previous algorithms fail. In general, our
algorithm requires only very mild restrictions on the (unknown) functional
relationship between yi and . We also consider the high dimensional
setting where beta* is sparse, and introduce a two-stage nonconvex framework that
addresses estimation challenges in high dimensional regimes where p ? n. For a
broad class of link functions between and yi , we establish minimax
lower bounds that demonstrate the optimality of our estimators in both the
classical and high dimensional regimes.
PMID- 28408791
TI - All-Trans Retinoic Acid Modulates TLR4/NF-kappaB Signaling Pathway Targeting TNF
alpha and Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative
Colitis and Colitis Associated Cancer.
AB - Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is
associated with bowel disease such as ulcerative colitis (UC). The data on role
of NF-kappaB signaling in development and progression of CAC were derived from
preclinical studies, whereas data from human are rare. The aim of this work was
to study the contribution of NF-kappaB pathway during UC and CAC, as well as the
immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the
expression of NOS2, TNF-alpha, TLR4, and NF-kappaB, in colonic mucosa. We also
studied NO/TNF-alpha modulation by LPS in colonic mucosa pretreated with AtRA. A
marked increase in TLR4, NF-kappaB, TNF-alpha, and NOS2 expression was reported
in colonic mucosa. The relationship between LPS/TLR4 and TNF-alpha/NO production,
as well as the role of NF-kappaB signaling, was confirmed by ex vivo experiments
and the role of LPS/TLR4 in NOS2/TNF-alpha induction through NF-kappaB pathway
was suggested. AtRA downregulates NOS2 and TNF-alpha expression. Collectively,
our study indicates that AtRA modulates in situ LPS/TLR4/NF-kappaB signaling
pathway targeting NOS2 and TNF-alpha expression. Therefore, we suggest that AtRA
has a potential value in new strategies to improve the current therapy, as well
as in the clinical prevention of CAC development and progression.
PMID- 28408794
TI - A Within-Group Analysis of African American Mothers' Authoritarian Attitudes,
Limit-Setting and Children's Self-Regulation.
AB - Research suggests that higher levels of authoritarian parenting exist in African
American (AA) families than in European American (EA) families, and that
authoritarian attitudes may be associated with more positive outcomes in AA
families than EA families. However, less is known about authoritarian attitudes
and children's development within AA families. This within-group study of 50
African American mothers and their 3-year-old children examined associations
between maternal authoritarian attitudes, observed maternal limit-setting
strategies, and children's self-regulation during a limit-setting interaction.
The findings indicate that while AA families may hold more authoritarian
attitudes than EA families, the direction of effect of authoritarian attitudes on
children's outcomes appears to be the same in both ethnic groups. In this sample,
when examining AA authoritarian attitudes relative to those of other AA mothers,
less or lower authoritarian attitudes were associated with authoritative limit
setting behavior (firm limits within the context of overall warmth and
responsiveness) and better children's self-regulation.
PMID- 28408796
TI - Old-Age Pension and Extended Families: How is Adult Children's Internal Migration
Affected?
AB - This paper makes use of the most recent social pension reform in rural China to
examine whether receipt of the pension payment equips adult children of
pensioners to migrate. Employing a regression discontinuity (hereafter RD) design
to a primary longitudinal survey, this paper overcomes challenges in the
literature that households eligible for pension payment might be systematically
different from ineligible households and that it is difficult to separate the
effect of pension from that of age or cohort heterogeneity. Around the pension
eligibility age cut-off, results reveal large and significant increase among
adult sons (but not daughters) to migrate out of their home county. Meanwhile,
adult children are more likely to migrate out if their parents are healthy. Our
Fuzzy RD estimations survive a standard set of key placebo tests and robustness
checks.
PMID- 28408795
TI - Epidemiology and Molecular Typing of Pregnancy-Associated Listeriosis Cases in
Lombardy, Italy, over a 10-Year Period (2005-2014).
AB - In developed countries, pregnancy-related listeriosis accounts for 20-43% of
total invasive listeriosis. This work describes the first pregnancy-related
listeriosis survey in Italy based on two data sources, that is, mandatory
notification system and regional laboratory-based network. Out of 610 listeriosis
cases reported over a 10-year period, 40 were pregnancy-related (6.6%). Among
these, 29 pregnancy-related isolates were available and have been analysed with
serotyping, Pulsed-Field Gel Electrophoresis, and Multi-Virulence-Locus Sequence
Typing. No maternal fatality was recorded, but 11 (29.7%) pregnancies resulted in
a foetal death, a miscarriage, or a birth of a foetus dying immediately after
birth. The average incidence of pregnancy-related listeriosis was 4.3 cases per
100000 births, and the proportion of pregnancy-associated listeriosis among
ethnic minorities was significantly higher compared to the general population
(30.0% versus 3.5%, P < 0.01). L. monocytogenes isolates belonged to serotypes
1/2a, 1/2b, and 4b, with the latter significantly more prevalent among pregnancy
related isolates. Twenty different pulsotypes were distinguished and 16 out of
the 29 isolates were classified into seven clusters. A total of 16 virulence
types (VTs) were identified. Five VTs accounted for 45% of the total cases and
coincided with those of previously described Epidemic Clones (ECs) of L.
monocytogenes.
PMID- 28408797
TI - Ocular hypotensive effects of a Rho-associated protein kinase inhibitor in
rabbits.
AB - PURPOSE: Ripasudil is a novel Rho-associated protein kinase inhibitor that is
used to treat ocular hypertension. However, the comparison of the intraocular
pressure (IOP)-lowering effects between ripasudil alone and other ocular
hypotensive drugs has not been studied thoroughly. The purpose of this study is
to examine the ocular hypotensive effects of 0.4% ripasudil, 2% pilocarpine, 0.5%
timolol and 0.1% dorzolamide in rabbits. We also studied the IOP changes when
0.4% ripasudil was combined with 2% pilocarpine, 0.5% timolol or 0.1%
dorzolamide. METHODS: One drop of saline solution, 0.4% ripasudil, 0.5% timolol,
2% pilocarpine or 1% dorzolamide or a combination of these agents was applied
topically to the left eyes of eight healthy albino rabbits. Posttreatment changes
in the IOP of albino rabbits were monitored using a rebound tonometer over a 5-h
time course. Changes in IOP after application of saline served as the control.
One-way analysis of variance and Dunnett's post hoc tests were used for
statistical analyses. RESULTS: After topical instillation, 0.4% ripasudil
resulted in significant decreases in IOP at 0.5 and 1 h compared with the control
group. Treatment with timolol, pilocarpine or dorzolamide had no significant
effect on IOP. Treatment with timolol, pilocarpine or dorzolamide in combination
with ripasudil resulted in significant reductions in IOP at 1 h. However, none of
these agents enhanced the IOP-lowering effects of ripasudil. CONCLUSION:
Ripasudil has stronger IOP-lowering effects than timolol, pilocarpine or
dorzolamide hypotensive agents in our rabbit model. Addition of timolol,
pilocarpine or dorzolamide did not enhance the IOP-lowering effects of ripasudil
alone.
PMID- 28408798
TI - An open randomized active-controlled clinical trial with low-dose SKA cytokines
versus DMARDs evaluating low disease activity maintenance in patients with
rheumatoid arthritis.
AB - BACKGROUND: Biologic agents are currently the strongest immunosuppressive drugs
able to induce remission in rheumatoid arthritis (RA). One of the objectives of
the medical scientific community now is how to maintain remission or low disease
activity (LDA). The aim of this trial is to evaluate the contribution of low-dose
sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10
fg/mL) in patients affected by RA in maintaining LDA or remission obtained after
biological therapy. METHOD: This is a randomized, open, active-controlled,
prospective, Phase IV trial. Disease activity score (DAS28), clinical disease
activity index, simplified disease activity index, erythrocyte sedimentation rate
and C-reactive protein levels, global health assessment, and pain visual analog
scale were evaluated at baseline visit and then every 3 months together with an
assessment of side effects till 12 months. Thirty-nine RA patients were enrolled
and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy
or to receive a combination of SKA low-dose cytokines formulated in concentration
of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive
months. RESULTS: The rate of maintenance of LDA at 12 months was superior in the
group treated with low-dose cytokines compared with patients treated with DMARDs,
66.7% and 42.1%, respectively; however, the difference between the groups was not
statistically significant. No side effects were reported in both groups.
CONCLUSION: This is the first study using a combination of three low-dose
cytokines in RA, after data published on psoriasis. These data suggest that the
use of a combination of low-dose SKA cytokines may be an opportunity to explore
in the management of RA.
PMID- 28408799
TI - The antiulcer effect of Cibotium barometz leaves in rats with experimentally
induced acute gastric ulcer.
AB - Cibotium barometz is a pharmaceutical plant customarily used in traditional
medicine in Malaysia for the treatment of different diseases, such as gastric
ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced
gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms
of medicinal properties. Seven groups of rats (normal control and ulcerated
control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz
correspondingly) were used in antiulcer experiment and pretreated with 10% Tween
20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas
absolute alcohol was fed orally to ulcerated control, omeprazole, and
experimental groups. Gastric's homogenate were assessed for endogenous enzymes
activities. Stomachs were examined macroscopically and histologically. Grossly,
the data demonstrated a significant decrease in the ulcer area of rats pretreated
with plant extract in a dose-dependent manner with respect to the ulcerated
group. Homogenates of the gastric tissue exhibited significantly increased
endogenous enzymes activities in rats pretreated with C. barometz extract
associated with the ulcerated control group. Histology of rats pretreated with C.
barometz extract group using hematoxylin and eosin staining exhibited a moderate
to-mild disruption of the surface epithelium with reduction in submucosal edema
and leucocyte infiltration in a dose-dependent manner. In addition, it showed
heat shock protein70 protein up-expression and BCL2-associated X protein
downexpression. These outcomes might be attributed to the gastroprotective and
antioxidative effects of the plant.
PMID- 28408800
TI - Rutin protects against neuronal damage in vitro and ameliorates doxorubicin
induced memory deficits in vivo in Wistar rats.
AB - Doxorubicin (DOX) is the most widely used broad-spectrum anticancer agent, either
alone or in combination, for most cancers including breast cancer. Long-term use
of chemotherapeutic agents to treat breast cancer patients results in cognitive
complications with a negative impact on survivors' quality of life. The study
objective was to evaluate rutin (RUT) for its neuroprotective effect against DOX
in human neuroblastoma (IMR32) cells in vitro and study its potential to
ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay
(3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), neurite growth
assay, detection of apoptosis by (acridine orange/ethidium bromide) staining,
intracellular reactive oxygen species (ROS) assay, and flowcytometric analysis
were carried out to assess neuroprotective potential against DOX. An in vivo
study was conducted for assessing protective effect of RUT against memory deficit
associated with DOX-induced chemobrain using object recognition task (ORT).
Locomotion was assessed using open field test. Serum biochemistry,
acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex
were assessed. Histopathological analysis of major organ systems was also carried
out. Prior exposure to RUT at 100 uM protected IMR32 cells from DOX (1 uM)
neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and
intracellular ROS generation with inhibition of neurite growth in differentiated
IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction
was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intra
peritoneal, once in 5 days), as we observed significant impairment of episodic
memory in ORT. Coadministration with RUT (50 mg/kg, per os) significantly
prevented memory deficits in vivo without any confounding influence on locomotor
activity. RUT also offered protection against DOX-induced myelosuppression,
cardiotoxicity, and nephrotoxicity. In conclusion, RUT may be a possible adjuvant
therapeutic intervention to alleviate cognitive and other complications
associated with DOX chemotherapy.
PMID- 28408801
TI - Effects of beta-d-mannuronic acid, as a novel non-steroidal anti-inflammatory
medication within immunosuppressive properties, on IL17, RORgammat, IL4 and GATA3
gene expressions in rheumatoid arthritis patients.
AB - Rheumatoid arthritis (RA) is the most common form of chronic inflammatory
arthritis characterized by pain, swelling and destruction of joints, with a
resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and
biological drugs can interfere with the disease process. In this study, the
effect of beta-d-mannuronic acid (M2000) as a novel non-steroidal anti
inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects
together with antioxidant effects was evaluated on IL17, RORgammat, IL4 and GATA3
gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate
(natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in
experimental models of multiple sclerosis, RA and nephrotic syndrome. This study
was performed on 12 patients with RA who had an inadequate response to
conventional treatments. During this trial, patients were permitted to continue
the conventional therapy excluding NSAIDs. M2000 was administered orally at a
dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells
(PBMCs) were collected before and after treatment to evaluate the expression
levels of IL4, GATA3, IL17 and RORgammat. The gene expression results showed that
M2000 has a potent efficacy, so that it could not only significantly decrease
IL17 and RORgammat levels but also increase IL4 and GATA3 levels after 12 weeks
of treatment. Moreover, the gene expression results were in accordance with the
clinical and preclinical assessments. In conclusion, M2000 as a natural novel
agent has therapeutic and immunosuppressive properties on RA patients
(identifier: IRCT2014011213739N2).
PMID- 28408802
TI - Mirtazapine for symptom control in refractory gastroparesis.
AB - INTRODUCTION: Gastroparesis symptoms can be severe and debilitating. Many
patients do not respond to currently available treatments. Mirtazapine has been
shown in case reports to reduce symptoms in gastroparesis. AIM: To assess the
efficacy and safety of mirtazapine in gastroparetic patients. METHODS: Adults
with gastroparesis and poorly controlled symptoms were eligible. Participants
were prescribed mirtazapine 15 mg PO qhs. Questionnaires containing the
gastrointestinal cardinal symptom index (GCSI) and the clinical patient grading
assessment scale (CPGAS) were completed by patients' pretreatment, at 2 weeks,
and at 4 weeks. Primary end point was nausea and vomiting response to mirtazapine
using the GCSI. Secondary end point was nausea and vomiting severity assessment
using the CPGAS. P-values were calculated using the paired two-tailed Student's t
test. Intention to treat analysis was used. RESULTS: A total of 30 patients aged
19-86 years were enrolled. Of those, 24 patients (80%) completed 4 weeks of
therapy. There were statistically significant improvements in nausea, vomiting,
retching, and perceived loss of appetite at 2 and 4 weeks (all P-values <0.05)
compared with pretreatment. There was a statistically significant improvement in
the CPGAS score at week 2 (P=0.003) and week 4 (P<0.001). Of the total patients,
14 (46.7%) experienced adverse effects from mirtazapine and due to this, 6
patients stopped therapy. CONCLUSION: Mirtazapine significantly improved both
nausea and vomiting in gastroparetics after 2 and 4 weeks of treatment. Side
effects led to treatment self-cessation in a fifth of patients. From these data,
we conclude that mirtazapine improves nausea and vomiting, among other symptoms,
in patients with gastroparesis and might be useful in select patients.
PMID- 28408803
TI - Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19
inhibitor and inducer.
AB - PURPOSE: A microdose drug-drug interaction (DDI) study may be a valuable tool for
anticipating drug interaction at therapeutic doses. This study aimed to compare
the magnitude of DDIs at microdoses and regular doses to explore the
applicability of a microdose DDI study. PATIENTS AND METHODS: Six healthy male
volunteer subjects were enrolled into each DDI study of omeprazole (victim) and
known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both
studies, the microdose (100 MUg, cold compound) and the regular dose (20 mg) of
omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor
or inducer was given daily, and the microdose and regular dose of omeprazole were
repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings
were performed at days 0, 1, 8, and 9 of both studies for noncompartmental
analysis. RESULTS: The magnitude of the DDI, the geometric mean ratios (with
perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the
curve to the last measurement (AUCt) of the microdose and the regular dose were
compared. The geometric mean ratios in the inhibition study were: 2.17 (micro)
and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the
induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16
(micro) and 0.15 (regular) for AUCt. There were no significant statistical
differences in the magnitudes of DDIs between microdose and regular-dose
conditions, regardless of induction or inhibition. CONCLUSION: Our results may be
used as partial evidence that microdose DDI studies may replace regular-dose
studies, or at least be used for DDI-screening purposes.
PMID- 28408804
TI - Spotlight on romiplostim in the treatment of children with chronic immune
thrombocytopenia: design, development, and potential place in therapy.
AB - Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by
isolated thrombocytopenia. In approximately one-third of cases, the duration of
thrombocytopenia will extend beyond 12 months consistent with a diagnosis of
chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe
or life-threatening bleeding complications are uncommon. Moreover, spontaneous
resolution occurs in the majority of children with chronic ITP necessitating
treatment in only those children with ongoing bleeding manifestations or
impairment in health-related quality of life (HRQOL). The characterization of
thrombopoietin (TPO) and remarkable advancements in our understanding of the
pathophysiology of ITP has led to the development of a new class of agents, the
TPO-receptor agonists that have documented efficacy in the amelioration of
thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a
second-generation TPO-receptor agonist that has undergone limited evaluation in
the treatment of chronic ITP in children. Evolving data suggest that romiplostim
may be a safe and effective agent in the treatment of chronic ITP in children.
Additional data are needed to confirm its ability to increase platelet counts,
decrease bleeding manifestation, and improve the HRQOL of children and caregivers
impacted by chronic ITP.
PMID- 28408805
TI - Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by
inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice.
AB - Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular
interstitial fibrosis are the main pathological changes of diabetic nephropathy
(DN), which is a common cause of end-stage renal disease. Previous studies have
suggested that berberine (BBR) has antifibrotic effects in the kidney and can
reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of
BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This
study was performed to explore the effects of BBR on the renal tubular EMT and
the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose
(HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed
that, relative to the model mice, the mice in the treatment group had an improved
general state and reduced blood glucose and 24-h urinary protein levels.
Degradation of renal function was ameliorated by BBR. We also observed the
protective effects of BBR on renal structural changes, including normalization of
an index of renal interstitial fibrosis and kidney weight/body weight. Moreover,
BBR suppressed the activation of the Notch/snail pathway and upregulated the
alpha-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to
prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch
pathway members and snail1 in mouse renal tubular epithelial cells. Our findings
indicate that BBR has a therapeutic effect on DN, including its inhibition of the
renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated
EMT inhibition occurs through Notch/snail pathway regulation.
PMID- 28408806
TI - Patient knowledge and pulmonary medication adherence in adult patients with
cystic fibrosis.
AB - BACKGROUND AND OBJECTIVES: Patient knowledge of lung function (ie, forced
expiratory volume in 1 s [FEV1]% predicted) and the intended benefits of their
prescribed pulmonary medications might play an important role in medication
adherence, but this relationship has not been examined previously in patients
with cystic fibrosis (CF). METHODS: All patients diagnosed with CF and without
prior lung transplantation were invited to complete knowledge and self-reported
medication adherence questionnaires during routine outpatient visits to the Adult
CF Clinic, St Paul's Hospital, Vancouver, Canada from June 2013 to August 2014.
RESULTS: A total of 142 out of 167 (85%) consecutive adults attending CF clinic
completed patient knowledge and medication adherence survey questionnaires. Sixty
four percent of the patients recalled their last FEV1% predicted value within 5%,
and 70% knew the intended benefits of all their prescribed medications. Self
reported adherence rates were highest for inhaled antibiotics (81%), azithromycin
(87%), and dornase alpha (76%) and lowest for hypertonic saline (47%).
Individuals who knew their FEV1% predicted value within 5% were more likely to
self-report adherence to dornase alpha (84% vs 62%, P=0.06) and inhaled
antibiotics (88% vs 64%, P=0.06) compared to those who did not, but these
associations were not statistically significant. There were no significant
associations observed between patient knowledge of intended medication benefits
and self-reported medication adherence. CONCLUSION: Contrary to our hypothesis,
disease- and treatment-related knowledge was not associated with self-reported
medication adherence. This suggests other barriers to medication adherence should
be targeted in future studies aiming to improve medication adherence in adults
with CF.
PMID- 28408807
TI - Comparison of oral health-related quality of life of patients treated by palatal
expanders with patients treated by fixed orthodontic appliances.
AB - INTRODUCTION AND PURPOSE: Wearing orthodontic appliances may negatively affect a
patient's oral health-related quality of life (OHRQoL) physiologically,
psychologically, and socially. Few studies have assessed the effect of palatal
expanders on OHRQoL. The aim of this study was to evaluate the impact of palatal
expanders on OHRQoL and to compare it with that of fixed orthodontic appliances.
MATERIALS AND METHODS: All adolescent and adult orthodontic patients who were
undergoing treatment with fixed appliances or palatal expanders between July 2015
and January 2016 in King Abdulaziz University Orthodontc Dental Clinics, were
recruited (n=399). The OHRQoL of each participant was assessed using the
shortened Arabic version of the Oral Health Impact Profile-14 questionnaire.
OHRQoL was compared between users of fixed appliances and users of palatal
expanders; it was also compared after stratifying the patients by gender. Chi
squared and Fisher's exact tests were used, as indicated. RESULTS: Palatal
expanders had significantly greater negative effects on chewing ability (P<=0.01)
and pronunciation (P=0.048). However, fixed orthodontic appliances had
significantly greater negative impacts on mouth aching (P=0.003), difficulty in
relaxing (P=0.01), irritability (P=0.001), and embarrassment (P<=0.01).
CONCLUSION: Palatal expanders had a significantly greater negative impact on some
aspects of OHRQoL when compared with fixed orthodontic appliances in adolescents
and young adults.
PMID- 28408809
TI - Assessment of effects of differences in trunk posture during Fowler's position on
hemodynamics and cardiovascular regulation in older and younger subjects.
AB - BACKGROUND: Downward shifts in blood volume with changing position generally
cause tachycardic responses. Age-related decreases in vagal nerve activity could
contribute to orthostatic hypotension in older individuals. Fowler's position is
a reclined position with the back between 30 degrees and 60 degrees , used to
facilitate breathing, eating, and other routine daily activities in frail and
elderly patients. OBJECTIVE: This study examined whether stroke volume (SV) was
higher and heart rate (HR) lower in Fowler's position with an upright upper trunk
than in Fowler's position with the whole trunk upright in both older and younger
subjects, based on the assumption that lower HR would result from reduced
sympathetic activation in older individuals. METHODS: We assessed hemodynamics
and HR variability from electrocardiography, noninvasive arterial pressure and
impedance cardiography in 11 younger male subjects (age range, 20-22 years) and
11 older male subjects (age range, 64-79 years), using three positions: supine,
or Fowler's positions with either 30 degrees of lower trunk inclination and 60
degrees of upper trunk inclination (UT60) or 60 degrees of whole trunk
inclination (WT60). Comparisons were then made between age groups and between
positions. RESULTS: Reductions in SV and tachycardic response were smaller with
UT60 than with WT60, in both younger and older subjects. In addition, reduced
tachycardic response with upright upper trunk appeared attributable to decreased
vagal withdrawal in younger subjects and to reduced sympathetic activation in
older subjects. CONCLUSION: Our findings indicate that an upright upper trunk
during Fowler's position allowed maintenance of SV and inhibited tachycardic
response compared to an upright whole trunk regardless of age, although the
autonomic mechanisms underlying tachycardic responses differed between younger
and older adults. An upright upper trunk in Fowler's position might help to
reduce orthostatic stress and facilitate routine activities and conversation in
frail patients.
PMID- 28408808
TI - Acute kidney injury and inflammatory response of sepsis following cecal ligation
and puncture in d-galactose-induced aging rats.
AB - BACKGROUND: Recently, the d-galactose (d-gal)-induced mimetic aging rat model has
been widely used in studies of age-associated diseases, which have shown that
chronic d-gal exposure induces premature aging similar to natural aging in rats.
With the increasing rate of sepsis in the geriatric population, an easy-access
animal model for preclinical studies of elderly sepsis is urgently needed. This
study investigates whether a sepsis model that is established in d-gal-induced
aging rats can serve as a suitable model for preclinical studies of elderly
patients with sepsis. OBJECTIVE: To investigate the acute kidney injury (AKI) and
inflammatory response of sepsis following cecal ligation and puncture (CLP) in d
gal-induced aging rats. METHODS: Twelve-week-old male Sprague Dawley rats were
divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500
mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6
weeks, the CLP method was used to establish a sepsis model. RESULTS: The
mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups,
respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase
associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor
alpha were markedly increased in the H d-gal group after establishment of the
sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of
severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal
groups and 80% for the H d-gal group. CONCLUSION: High-dose- d-gal-induced aging
rats are more likely to die from sepsis than are young rats, and probably this is
associated with increased severity of septic AKI and an increased inflammatory
response. Therefore, use of the high-dose- d-gal-induced aging rat model of
sepsis for preclinical studies can provide more useful information for the
treatment of sepsis in elderly patients.
PMID- 28408810
TI - Prevalence and pattern of the elongated styloid process among geriatric patients
in Saudi Arabia.
AB - OBJECTIVE: The objectives of this study were to assess the elongation of the
styloid process on digital panoramic radiographs and to evaluate the prevalence
of the elongation according to age, sex and types. PATIENTS AND METHODS: Digital
panoramic radiographs of 198 geriatric edentulous patients were analyzed. The
radiographic length of the styloid process was measured on both sides using the
measurement toolbars on the accompanying analysis software. For statistical
analysis, Student's t-test, chi-square test and analysis of variance test were
used. RESULTS: The elongated styloid process was seen in 87 of the 198 patients.
It was observed that as age increased, elongation of the styloid process
increased with a male predominance. Type I elongation was more common than other
types of elongation. Bilateral elongation was most commonly found than unilateral
elongation, and both types of elongation were frequently seen in males compared
with females. CONCLUSION: The prevalence of the elongated styloid process in the
present study was higher in comparison to the other reports from edentulous
patients.
PMID- 28408811
TI - Systematic review on strength training in Parkinson's disease: an unsolved
question.
AB - The purpose of this study was to investigate the effectiveness of strength
training, performed against a different resistance from body weight, in improving
motor and nonmotor symptoms in patients with Parkinson's disease (PD). The
following electronic databases were searched: PubMed, Physiotherapy Evidence
Database, Cochrane Central Register of Controlled Trials, Scopus, and Web of
Science. The review was conducted and reported in accordance with the PRISMA
statement. Thirteen high-quality randomized controlled trials were included.
Strength training performed against external resistance is well tolerated and
appears to be a suitable physical activity to improve both physical parameters
and quality of life parameters of PD subjects. However, although the study
intervention included strength training, only a few selected studies assessed the
improvement of muscle strength. Despite the encouraging results, it is difficult
to establish a correlation between strength training and the improvements made.
Our review highlights the lack of common intent in terms of study design and the
presence of different primary and secondary outcomes. Accordingly, further
studies are needed to support the beneficial effects of different types of
strength training in PD subjects and to underline the superiority of strength
training in PD patients with respect to other training.
PMID- 28408812
TI - Relationship between jaw opening force and hyoid bone dynamics in healthy elderly
subjects.
AB - PURPOSE: This study aimed to examine the relationship between jaw opening force
and hyoid bone dynamics and resting position in elderly individuals based on
gender. SUBJECTS AND METHODS: Subjects were 36 healthy elderly individuals aged
>=65 years without dysphagia (16 men and 20 women; mean age 75.5 years, range 65
88 years). Videofluorographic images during the swallowing of 10 mL of 40% (w/v)
barium sulfate were obtained and the degrees of anterior, superior, and
hypotenuse displacements of the hyoid bone and maximum/resting hyoid position
were evaluated. Jaw opening force was measured three times using a jaw opening
force sthenometer; the mean of these three measurements was used for analysis.
RESULTS: In men, there was a positive correlation between jaw opening force and
resting hyoid position and negative correlations among all the degrees of
anterior, superior, and hypotenuse displacements of the hyoid bone. In women,
there was no statistically significant correlation between jaw opening force and
any of the measurement items. There was no statistically significant correlation
between jaw opening force and maximum hyoid position in either men or women.
CONCLUSION: Our findings suggest that low jaw opening force leads to low resting
hyoid position only in elderly men, and a lower hyoid position in healthy elderly
men results in a larger total amount of hyoid displacement during swallowing.
Moreover, a maximum hyoid position in healthy individuals of either gender does
not differ depending on their jaw opening force.
PMID- 28408813
TI - COPD is commonly underdiagnosed in patients with lung cancer: results from the
RECOIL study (retrospective study of COPD infradiagnosis in lung cancer).
AB - INTRODUCTION: Many patients with COPD are underdiagnosed, including patients with
coexisting lung cancer. METHODS: We conducted a retrospective study of COPD
prevalence and outcomes among all patients diagnosed with lung cancer at our
institution during a 2-year period. Patients with known COPD (group A) were
compared with those who received a diagnosis of COPD at the time of their
oncologic workup (group B). RESULTS: A total of 306 patients were diagnosed with
lung cancer during the study period, including 87 with COPD (28.6%). Sixty
percent of patients with coexisting lung cancer and COPD were unaware of their
obstructive airways disease prior to the lung cancer diagnosis. Patients in group
A were older (74+9 vs 69+9 years; P=0.03), had more severe obstruction (% of
predicted forced expiratory volume in one second [FEV1%] 55+17 vs 71+13; P=0.04),
more emphysema (91% vs 65%; P=0.02), and worse diffusing capacity of the lungs
for carbon monoxide 59+19% vs 72+22%; P=0.01) than patients in group B, but the
latter had more advanced lung cancer (27.3% vs 13.8% stage IV disease; P=0.01)
and consumed more outpatient resources (P=0.03). Overall mortality was similar
(56% vs 58%). However, stage-adjusted mortality showed a trend toward greater
mortality in group B patients (1.87 [0.91-3.85]; P=0.087). CONCLUSION: COPD
infradiagnosis is common in patients with coexisting lung cancer and is
associated with more advanced cancer stage, greater outpatient resource
consumption, and may be associated with greater stage-adjusted mortality.
PMID- 28408814
TI - Non-invasive ventilation with intelligent volume-assured pressure support versus
pressure-controlled ventilation: effects on the respiratory event rate and sleep
quality in COPD with chronic hypercapnia.
AB - BACKGROUND: COPD patients who develop chronic hypercapnic respiratory failure
have a poor prognosis. Treatment of choice, especially the best form of
ventilation, is not well known. OBJECTIVES: This study compared the effects of
pressure-controlled (spontaneous timed [ST]) non-invasive ventilation (NIV) and
NIV with intelligent volume-assured pressure support (IVAPS) in chronic
hypercapnic COPD patients regarding the effects on alveolar ventilation, adverse
patient/ventilator interactions and sleep quality. METHODS: This prospective,
single-center, crossover study randomized patients to one night of NIV using ST
then one night with the IVAPS function activated, or vice versa. Patients were
monitored using polysomnography (PSG) and transcutaneous carbon dioxide pressure
(PtcCO2) measurement. Patients rated their subjective experience (total score, 0
45; lower scores indicate better acceptability). RESULTS: Fourteen patients were
included (4 females, age 59.4+/-8.9 years). The total number of respiratory
events was low, and similar under pressure-controlled (5.4+/-6.7) and IVAPS
(8.3+/-10.2) conditions (P=0.064). There were also no clinically relevant
differences in PtcCO2 between pressure-controlled and IVAPS NIV (52.9+/-6.2
versus 49.1+/-6.4 mmHg). Respiratory rate was lower under IVAPS overall; between
group differences reached statistical significance during wakefulness and non
rapid eye movement sleep. Ventilation pressures were 2.6 cmH2O higher under IVAPS
versus pressure-controlled ventilation, resulting in a 20.1 mL increase in
breathing volume. Sleep efficiency was slightly higher under pressure-controlled
ventilation versus IVAPS. Respiratory arousals were uncommon (24.4/h [pressure
controlled] versus 25.4/h [IVAPS]). Overall patient assessment scores were
similar, although there was a trend toward less discomfort during IVAPS.
CONCLUSION: Our results show that IVAPS NIV allows application of higher
nocturnal ventilation pressures versus ST without affecting sleep quality or
inducing ventilation- associated events.
PMID- 28408815
TI - Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of
COPD exacerbations: a multicenter prospective blinded study.
AB - BACKGROUND: Exacerbations of COPD (ECOPD) are a frequent cause of emergency room
(ER) visits. Predictors of early outcome could help clinicians in orientation
decisions. In the current study, we investigated whether mid-regional pro
adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation,
could predict short-term outcomes. PATIENTS AND METHODS: This prospective blinded
observational study was conducted in 20 French centers. Patients admitted to the
ER for an ECOPD were considered for inclusion. A clinical risk score was
calculated, and MR-proADM and copeptin levels were determined from a venous blood
sample. The composite primary end point comprised 30-day death or transfer to the
intensive care unit or a new ER visit. RESULTS: A total of 379 patients were
enrolled in the study, of whom 277 were eventually investigated for the primary
end point that occurred in 66 (24%) patients. In those patients, the median
(interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77-1.48) versus
0.83 nmol/L (0.63-1.07) in patients who did not meet the primary end point
(P=0.0009). In contrast, copeptin levels were similar in patients who met or did
not meet the primary end point (P=0.23). MR-proADM levels increased with
increasing clinical risk score category: 0.74 nmol/L (0.57-0.89), 0.83 nmol/L
(0.62-1.12) and 0.95 nmol/L (0.75-1.29) for the low-, intermediate- and high-risk
categories, respectively (P<0.001). MR-proADM was independently associated with
the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10-2.48;
P=0.015). MR-proADM predicted the occurrence of primary end point with a
sensitivity of 46% (95% CI, 33%-58%) and a specificity of 79% (95% CI, 74-84).
CONCLUSION: MR-proADM but not copeptin was significantly associated with outcomes
at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM,
alone or combined with the clinical risk score, was a moderate strong predictor
of short-term outcomes.
PMID- 28408816
TI - Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system
for the treatment of acute spinal cord injury.
AB - Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited
regenerative capacity of the adult central nervous system. Nanomicelles can be
used as therapeutic systems to provide effective treatments for SCI. In this
study, a novel triblock monomethyl poly(ethylene glycol)-poly(l-lactide)
poly(trimethylene carbonate) copolymer was successfully synthesized. Next,
polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug
Administration-approved antiepileptic drug, were prepared and characterized. The
ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in
vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good
solubility and dispersibility. Additionally, these controlled-release micelles
showed significant antioxidative and neuron-protective effects in vitro. Finally,
our results indicated that ZNS-M treatment could promote motor function recovery
and could increase neuron and axon density in a hemisection SCI model. In
summary, these results may provide an experimental basis for the use of ZNS-M as
a clinically applicable therapeutic drug for the treatment of SCI in the future.
PMID- 28408817
TI - Shape-dependent antibacterial effects of non-cytotoxic gold nanoparticles.
AB - Gold nanoparticles (AuNPs) of various shapes (including spheres, stars and
flowers), with similar dimensions, were synthesized and evaluated for their
antibacterial effects toward Staphylococcus aureus, a bacterium responsible for
numerous life-threatening infections worldwide. Optical growth curve measurements
and Gompertz modeling showed significant AuNP shape- and concentration-dependent
decreases in bacterial growth with increases in bacterial growth lag time. To
evaluate prospective use in in vivo systems, the cytotoxicity of the same AuNPs
was evaluated toward human dermal fibroblasts in vitro by 3-(4,5 dimethylthiazol
2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability
assays and confocal microscopy. No indication of any mammalian cell toxicity or
morphological effects was found. Additionally, it was observed that the AuNPs
were readily internalized in fibroblasts after 4 days of incubation. Most
importantly, the results of the present study showed that gold nanoflowers in
particular possessed the most promising non-cytotoxic mammalian cell behavior
with the greatest shape-dependent antibacterial activity-promising properties for
their future investigation in a wide range of anti-infection applications.
PMID- 28408818
TI - Anti-inflammatory activity of niosomes entrapped with Plai oil (Zingiber
cassumunar Roxb.) by therapeutic ultrasound in a rat model.
AB - OBJECTIVE: The aim of this study was to evaluate the antioxidant and anti
inflammatory activities of Plai oil-encapsulated niosomes (Zingiber cassumunar
Roxb.) on inflamed subcutaneous Wistar rat skin by therapeutic ultrasound.
METHODS: Pure oil from Plai rhizomes was extracted by steam distillation, and
antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl radical
scavenging assay. Bioactive compounds were analyzed by gas chromatography-mass
spectrometry. Niosome particles containing Plai oil were prepared by chloroform
film method with sonication before testing for anti-inflammatory activity on
locally inflamed subcutaneous rat skin after inducement from lipopolysaccharide
with ultrasound once a day for 3 days. Skin temperatures and blood flow were
evaluated. RESULTS: Plai oil presented antioxidant activity that inhibited 2,2
diphenyl-1-picrylhydrazyl radicals. Four active compounds found in the essential
oil were sabinene, gamma-terpinene, terpinene-4-ol, and (E)-1-(3,4-dimethyoxy
phenyl) butadiene. Application of ultrasound (0.2 W/cm2, 20%, 3 min) with gel
containing Plai oil-encapsulated niosomes decreased skin temperature and blood
flow to the lowest level compared to the application of neurofen drug or gel
based control. CONCLUSION: Plai oil, which consists of four main bioactive
compounds and possesses antioxidant and anti-inflammatory activities, can be
applied against local subcutaneous inflammation when used with therapeutic
ultrasound via entrapped niosomes.
PMID- 28408819
TI - Simvastatin nanoparticles attenuated intestinal ischemia/reperfusion injury by
downregulating BMP4/COX-2 pathway in rats.
AB - The purpose of the research was to explore the therapeutic action of simvastatin
loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on
intestinal ischemia/reperfusion injury (II/RI) through downregulating bone
morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to
free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim
or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of
ischemia and 1 h of reperfusion. The blood and small intestines were collected,
serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL
10), tumor necrosis factor-alpha, and nitric oxide (NO) were checked, and the
dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content,
reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa
phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein
kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and
Sim/P pretreatment reduced intestinal oxidative damnification, restricted
inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared
to II/RI groups, while Sim/P remarkably improved this effect.
PMID- 28408820
TI - Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor
and anti-inflammation efficacy.
AB - At present, it has become evident that inflammation plays a critical role in
tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been
suggested as a promising strategy in cancer treatment. In this study, novel redox
responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan
S-S-hexadecyl (C16-SS-CS-mPEG). These micelles were able to carry and deliver
drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)
chitosan-C-C-hexadecyl (C16-CC-CS-mPEG) was developed in a similar fashion to
that used to yield C16-CC-CS-mPEG without a redox-responsive disulfide bond. The
cellular uptake mechanisms of both micelles were determined. The efficient
intracellular drug release from micelles in MCF-7 cells was further confirmed.
Results indicated that curcumin (Cur) could rapidly form C16-SS-CS-mPEG@ Cur
micelles when exposed to reducing agents and efficaciously enhance intracellular
accumulation. The cytotoxicity assay demonstrated that C16-SS-CS-mPEG@Cur
exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay
results indicated that C16-SS-CS-mPEG@Cur treatment significantly downregulated
tumor necrosis factor (TNF-alpha) expression and showed good anti-inflammatory
effects in tumor microenvironment. Most importantly, antitumor effects in vivo
showed satisfactory therapeutic effects with C16-SS-CS-mPEG@Cur. Hence, C16-SS-CS
mPEG@Cur micelles can be useful in tumor therapy.
PMID- 28408821
TI - Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin
conjugate.
AB - Development of antibody-drug conjugates (ADCs) is a promising therapeutic
strategy for cancer therapy. In this study, folate was conjugated via a
polyethyleneglycol (PEG) linker to immunoglobulin G (IgG), which was linked to
doxorubicin (DOX), to form a novel ADC folate-PEG-IgG-DOX (FA-PEG-IgG-DOX). The
FA-PEG-IgG-DOX showed high targeting efficiency in HeLa and KB cells and
significantly improved the uptake and retention of DOX compared with IgG-DOX
about 10-fold. Subsequently, FA-PEG-IgG-DOX was shown to have at least 8 times
higher antitumor activity than IgG-DOX both in HeLa and KB cells and also induced
more apoptosis in those cells than IgG-DOX. Moreover, FA-PEG-IgG-DOX had a 2
times longer circulating time than FA-IgG-DOX, but did not increase the DOX
distribution in mouse hearts. Importantly, FA-PEG-IgG-DOX treatment significantly
inhibited tumor growth in xenograft mice. Together, our results indicate that FA
PEG-IgG is an effective ADC carrier for delivery of chemotherapeutic agents and
that conjugating tumor targeting ligands to antibodies is a promising strategy
for producing ADC drugs.
PMID- 28408822
TI - Negatively charged silver nanoparticles with potent antibacterial activity and
reduced toxicity for pharmaceutical preparations.
AB - BACKGROUND: The discovery of new solutions with antibacterial activity as
efficient and safe alternatives to common preservatives (such as parabens) and to
combat emerging infections and drug-resistant bacterial pathogens is highly
expected in cosmetics and pharmaceutics. Colloidal silver nanoparticles (NPs) are
attracting interest as novel effective antimicrobial agents for the prevention of
several infectious diseases. METHODS: Water-soluble, negatively charged silver
nanoparticles (AgNPs) were synthesized by reduction with citric and tannic acid
and characterized by transmission electron microscopy, dynamic light scattering,
zeta potential, differential centrifuge sedimentation, and ultraviolet-visible
spectroscopy. AgNPs were tested with model Gram-negative and Gram-positive
bacteria in comparison to two different kinds of commercially available AgNPs.
RESULTS: In this work, AgNPs with higher antibacterial activity compared to the
commercially available colloidal silver solutions were prepared and investigated.
Bacteria were plated and the antibacterial activity was tested at the same
concentration of silver ions in all samples. The AgNPs did not show any
significant reduction in the antibacterial activity for an acceptable time
period. In addition, AgNPs were transferred to organic phase and retained their
antibacterial efficacy in both aqueous and nonaqueous media and exhibited no
toxicity in eukaryotic cells. CONCLUSION: We developed AgNPs with a 20 nm
diameter and negative zeta potential with powerful antibacterial activity and low
toxicity compared to currently available colloidal silver, suitable for cosmetic
preservatives and pharmaceutical preparations administrable to humans and/or
animals as needed.
PMID- 28408823
TI - Gold nanoparticles enhance TRAIL sensitivity through Drp1-mediated apoptotic and
autophagic mitochondrial fission in NSCLC cells.
AB - Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its
agonistic receptors have been identified as highly promising antitumor agents
preferentially eliminating cancer cells with minimal damage, the emergence of
TRAIL resistance in most cancers may contribute to therapeutic failure. Thus,
there is an urgent need for new approaches to overcome TRAIL resistance. Gold
nanoparticles (AuNPs) are one of the most promising nanomaterials that show
immense antitumor potential via targeting various cellular and molecular
processes; however, the effects of AuNPs on TRAIL sensitivity in cancer cells
remain unclear. In this study, we found that AuNPs combined with TRAIL exhibited
a greater potency in promoting apoptosis in non-small-cell lung cancer (NSCLC)
cells compared with TRAIL alone, suggesting that AuNPs sensitize cancer cells to
TRAIL. Further experiments demonstrated that the combination of TRAIL and AuNPs
was more effective in causing excessive mitochondrial fragmentation in cancer
cells accompanied by a dramatic increase in mitochondrial recruitment of dynamin
related protein 1 (Drp1), mitochondrial dysfunctions, and enhancement of
autophagy induction. Small interfering RNA (siRNA) silencing of Drp1 or
inhibition of autophagy could effectively alleviate apoptosis in cells exposed to
TRAIL combined with AuNPs. In vivo studies revealed that AuNPs augmented TRAIL
sensitivity in tumor-bearing mice. Our data indicated that AuNPs potentiate
apoptotic response to TRAIL in NSCLC cells through Drp1-dependent mitochondrial
fission, and TRAIL combined with AuNPs can be a potential chemotherapeutic
strategy for the treatment of NSCLC.
PMID- 28408824
TI - Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness
of cancer cells via inhibition of the Wnt signaling pathway.
AB - Disordered copper metabolism plays a critical role in the development of various
cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs)
exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate
cancer is a frequently diagnosed male malignancy prone to relapse, and castration
resistance is the main reason for endocrine therapy failure. However, whether
CONPs have the potential to treat castration-resistant prostate cancer is still
unknown. Here, using the castration-resistant PC-3 human prostate cancer cell
line as a model, we report that CONPs can selectively induce apoptosis and
inhibit the proliferation of cancer cells in vitro and in vivo without affecting
normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer
cells and inhibit the Wnt signaling pathway, both of which highlight the great
potential of CONPs as a new clinical castration-resistant prostate cancer
therapy.
PMID- 28408825
TI - A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with
minimal increase in size.
AB - In this study, we describe the experiments determining whether coating gold
nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant
advantages, such as increased serum half-life and resistance to protein
adsorption. Monodisperse TEG-coated, NaBH4-reduced gold nanoparticles with a
hydrodynamic size comparable to albumin were synthesized by reducing gold
chloride with NaBH4 under alkaline conditions in the presence of TEG-SH. The
particles were characterized by gel electrophoresis, column chromatography, and
transmission electron microscopy. The nanoparticles were subsequently injected
intravenously into mice, and their half-lives and final destinations were
determined via photometric analysis, light microscopy (LM), and transmission
electron microscopy. The TEG particles had a long half-life (~400 minutes) that
was not influenced by splenectomy. After 500 minutes of injection, TEG particles
were found in kidney proximal tubule cell vesicles and in spleen red and white
pulp. The particles induced apoptosis in the spleen red pulp but not in white
pulp or the kidney. Some of the TEG particles appeared to have undergone ligand
exchange reactions that increased their charge. The TEG particles were shown to
be resistant to nonspecific protein adsorption, as judged by gel electrophoresis
and column chromatography. These results demonstrate that naturally monodisperse,
small-sized gold nanoparticles coated with TEG have long in vivo plasma half
lives, are minimally toxic, and are resistant to protein adsorption. This
suggests that a TEG coating should be considered as an alternative to a
polyethylene glycol coating, which is polydisperse and of much larger size.
PMID- 28408826
TI - Durable antibacterial and UV-protective Ag/TiO2@ fabrics for sustainable
biomedical application.
AB - A facile method was developed to endow cotton fabric with remarkable
antibacterial and ultraviolet (UV)-protective properties. The flower-like TiO2
micro-nanoparticles were first deposited onto cotton fabric surface via
hydrothermal deposition method. Then, the Ag NPs with a high deposition density
were evenly formed onto TiO2@cotton surface by sodium hydroxide solution
pretreatment and followed by in situ reduction of ANO3. This work focused on the
influence of different hydrothermal reaction durations and the concentration of
AgNO3 on antibacterial activity against relevant microorganisms in medicine as
well as on the UV-blocking property. Ag NPs-loaded TiO2@cotton exhibited high
antibacterial activity with an inhibition rate higher than 99% against
Staphylococcus aureus and Escherichia coli bacteria. Moreover, the as-prepared
cotton fabric coated with Ag NPs and TiO2 NPs demonstrated outstanding UV
protective ability with a high ultraviolet protection factor value of 56.39.
Morphological image of the cells revealed a likely loss of viability as a result
of the synergistically biocidal effects of TiO2 and Ag on attached bacteria.
These results demonstrate a facile and robust synthesis technology for
fabricating multifunctional textiles with a promising biocidal activity against
common Gram-negative and Gram-positive bacteria.
PMID- 28408827
TI - Photothermal-modulated drug delivery and magnetic relaxation based on
collagen/poly(gamma-glutamic acid) hydrogel.
AB - Injectable and stimuli-responsive hydrogels have attracted attention in molecular
imaging and drug delivery because encapsulated diagnostic or therapeutic
components in the hydrogel can be used to image or change the microenvironment of
the injection site by controlling various stimuli such as enzymes, temperature,
pH, and photonic energy. In this study, we developed a novel injectable and
photoresponsive composite hydrogel composed of anticancer drugs, imaging contrast
agents, bio-derived collagen, and multifaceted anionic polypeptide, poly (gamma
glutamic acid) (gamma-PGA). By the introduction of gamma-PGA, the intrinsic
temperature-dependent phase transition behavior of collagen was modified to a low
viscous sol state at room temperature and nonflowing gel state around body
temperature. The modified temperature-dependent phase transition behavior of
collagen/gamma-PGA hydrogels was also evaluated after loading of near-infrared
(NIR) fluorophore, indocyanine green (ICG), which could transform absorbed NIR
photonic energy into thermal energy. By taking advantage of the abundant
carboxylate groups in gamma-PGA, cationic-charged doxorubicin (Dox) and
hydrophobic MnFe2O4 magnetic nanoparticles were also incorporated successfully
into the collagen/gamma-PGA hydrogels. By illumination of NIR light on the
collagen/gamma-PGA/Dox/ICG/MnFe2O4 hydrogels, the release kinetics of Dox and
magnetic relaxation of MnFe2O4 nanoparticles could be modulated. The experimental
results suggest that the novel injectable and NIR-responsive collagen/gamma-PGA
hydrogels developed in this study can be used as a theranostic platform after
loading of various molecular imaging probes and therapeutic components.
PMID- 28408828
TI - Access to diagnosis, treatment, and supportive services among pharmacotherapy
treated children/adolescents with ADHD in Europe: data from the Caregiver
Perspective on Pediatric ADHD survey.
AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most
common childhood psychiatric disorders and negatively impacts caregivers' lives.
Factors including barriers to accessing care, dissatisfaction with support
services, and lack of caregiver resources may contribute to this. OBJECTIVES: To
report caregivers' experiences of ADHD diagnosis, behavioral therapy (BT), and
supportive care for children/adolescents with ADHD. METHODS: The Caregiver
Perspective on Pediatric ADHD (CAPPA) survey included caregivers of
children/adolescents (6-17 years) from ten European countries who were currently
receiving/had received ADHD pharmacotherapy in the previous 6 months. Caregivers
reported experiences of obtaining an ADHD diagnosis, access to BT, availability
of caregiver resources, and level of health care/school support. Pan-EU and
country-specific descriptive statistics are reported; responses were compared
across countries. RESULTS: Of 3,616 caregivers, 66% were female. Mean age of
children/adolescents was 11.5 years; 80% were male. Mean time from the first
doctor visit to diagnosis was 10.8 (95% confidence interval 10.2, 11.3) months;
31% of caregivers reported the greatest degrees of difficulty in obtaining an
ADHD diagnosis; 44% of children/adolescents did not receive BT. Forty-seven
percent of caregivers reported that sufficient resources were available, 44% were
"very satisfied"/"satisfied" with medical care, and 50% found health care
providers "very supportive"/"somewhat supportive". Mainstream schools were
attended by 82% of children/adolescents. Of those, 67% of caregivers thought
schools could help more with the child/adolescent's ADHD and 48% received extra
help/special arrangement. Results varied significantly between countries
(P<0.001, all parameters). CONCLUSION: Almost a third of caregivers reported a
high degree of difficulty in obtaining an ADHD diagnosis for their
child/adolescent, less than half felt that sufficient resources were available,
and gaps in support from health care providers/schools were identified. Findings
underscore the need to improve access to diagnosis and provision of supportive
services to enable better standards of care, and potentially reduce the impact of
child/adolescent ADHD on caregivers' lives.
PMID- 28408829
TI - Sleep apnea and the subsequent risk of Parkinson's disease: a 3-year nationwide
population-based study.
AB - PURPOSE: Sleep apnea (SA)-induced chronic intermittent hypoxia increases
oxidative stress and inflammation, which may contribute to the pathophysiology of
Parkinson's disease (PD). This study evaluated the risk of PD following SA
diagnosis. PATIENTS AND METHODS: This was a 3-year nationwide population-based
matched cohort study using claims data from the National Health Insurance
Research Database (NHIRD), Taiwan. We analyzed 1,944 patients diagnosed as having
SA between 1997 and 2005 and a matched cohort of 9,720 non-SA patients from the
NHIRD. Patients with a history of PD were excluded. Each patient was followed up
for 3 years to evaluate subsequent PD development. RESULTS: Of the 11,664
patients, 17 (0.9%) and 38 (0.4%) from the SA and matched non-SA cohorts,
respectively, were subsequently diagnosed as having PD during follow-up. After
adjustments for potential confounders, the SA cohort had a 1.85-fold higher risk
of PD than the non-SA cohort (95% confidence interval [CI] =1.02-3.35; P=0.042).
After age and sex stratification, PD development was independently associated
with SA only in men (adjusted hazard ratio [HR], 2.26; 95% CI =1.11-4.63; P<0.05)
and in patients aged >=60 years (adjusted HR, 1.93; 95% CI =1.01-3.71; P<0.05).
CONCLUSION: Our study suggests that patients with SA are at an increased
longitudinal risk of PD. Furthermore, age and male sex are independently
associated with the risk of PD.
PMID- 28408830
TI - Twelve-week physical exercise does not have a long-lasting effect on kynurenines
in plasma of depressed patients.
AB - BACKGROUND: Physical exercise has well-characterized positive effects on
depressive symptoms. The underlying biologic mechanisms are, however, far from
established. A recently discovered mechanism has linked the enhanced conversion
of kynurenine to kynurenic acid (KYNA) to an increased resilience toward stress
induced depression in mice. The aim of this study was to translate these findings
to humans. MATERIALS AND METHODS: Kynurenine and KYNA levels were measured by
high-performance liquid chromatography in plasma samples from 117 patients
affected by mild-to-moderate depression before and within a week after a 12-week
training period at three different intensities. The patients were part of the
Regassa study. RESULTS: No differences in plasma levels of kynurenine and KYNA or
in their ratio could be detected between before and after training. No effect of
the intensity group could be observed. No correlation with the improvement in
cardiovascular fitness (Astrand score) or the improvement in mood (Montgomery
Asberg Depression Rating Scale score) could be observed. LIMITATIONS: As the
Regassa study is based on an intention-to-treat protocol, the exact time and the
exact intensity of the physical exercise are not known. Analyses of pulse data as
well as personal interviews, however, were used to control the exercise
protocols. Furthermore, the observations reflect chronic changes. CONCLUSION:
Physical exercise positively affects mood and cardiovascular fitness, but does
not lead to long-lasting changes in plasma levels of kynurenine and KYNA in
patients affected by mild-to-moderate depression.
PMID- 28408831
TI - Modulation of the activity of N-methyl-d-aspartate receptors as a novel treatment
option for depression: current clinical evidence and therapeutic potential of
rapastinel (GLYX-13).
AB - Classical monoaminergic antidepressants show several disadvantages, such as
protracted onset of therapeutic action. Conversely, the fast and sustained
antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist
ketamine raises vast interest in understanding the role of the glutamate system
in mood disorders. Indeed, numerous data support the existence of glutamatergic
dysfunction in major depressive disorder (MDD). Drawback to this short-latency
therapy is its side effect profile, especially the psychotomimetic action, which
seriously hampers the common and widespread clinical use of ketamine. Therefore,
there is a substantial need for alternative glutamatergic antidepressants with
milder side effects. In this article, we review evidence that implicates NMDARs
in the prospective treatment of MDD with focus on rapastinel (formerly known as
GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect,
which acts by enhancing NMDAR function as opposed to blocking it. We summarize
and discuss current clinical and animal studies regarding the therapeutic
potential of rapastinel not only in MDD but also in other psychiatric disorders,
such as obsessive-compulsive disorder and posttraumatic stress disorder.
Additionally, we discuss current data concerning the molecular mechanisms
underlying the antidepressant effect of rapastinel, highlighting common aspects
as well as differences to ketamine. In 2016, rapastinel received the Breakthrough
Therapy designation for the treatment of MDD from the US Food and Drug
Administration, representing one of the most promising alternative
antidepressants under current investigation.
PMID- 28408832
TI - Punding following posterior cerebral artery infarction: a case report and
literature review.
AB - INTRODUCTION: Punding is a complex stereotyped behavior, characterized by
excessiveness, non-goal orientation, and repetitiveness. It is mostly associated
with Parkinson's disease, and very few cases in non-Parkinson's disease have been
reported. We report a case of punding associated with supratentorial ischemic
stroke. CASE PRESENTATION: We present a 70-year-old man with left posterior
cerebral artery infarction with quetiapine-induced punding manifesting as
repetitive unidirectional body turning. Remission of punding behavior ensued
after cessation of quetiapine and administration of clonazepam. CONCLUSION: This
case describes the clinical course of quetiapine-induced punding in a patient
with left posterior cerebral artery infarction. It suggests clonazepam may serve
as a treatment option for poststroke punding.
PMID- 28408833
TI - An Internet-based program for depressive symptoms using human and automated
support: a randomized controlled trial.
AB - PURPOSE: The purpose of this study was to analyze the efficacy of an Internet
based program for depressive symptoms using automated support by information and
communication technologies (ICTs) and human support. PATIENTS AND METHODS: An
Internet-based program was used to teach adaptive ways to cope with depressive
symptoms and daily problems. A total of 124 participants who were experiencing at
least one stressful event that caused interference in their lives, many of whom
had clinically significant depressive symptoms, were randomly assigned into
either an intervention group with ICT support (automated mobile phone messages,
automated emails, and continued feedback through the program); an intervention
group with ICT support plus human support (brief weekly support phone call
without clinical content); or a waiting-list control. At pre-, post-, and 12
month follow-up, they completed depression, anxiety, positive and negative
effect, and perceived stress measures. Results were analyzed using both intention
to-treat and completers data. The majority were women (67.7%), with a mean age of
35.6 years (standard deviation =9.7). RESULTS: The analysis showed that the two
intervention groups improved significantly pre- to posttreatment, compared with
the control group. Furthermore, improvements were maintained at the 12-month
follow-up. Adherence and satisfaction with the program was high in both
conditions. CONCLUSION: The Internet-based program was effective and well
accepted, with and without human support, showing that ICT-based automated
support may be useful. It is essential to continue to study other ICT strategies
for providing support.
PMID- 28408834
TI - Predictive values of D-dimer assay, GRACE scores and TIMI scores for adverse
outcome in patients with non-ST-segment elevation myocardial infarction.
AB - PURPOSE: To determine the predictive values of D-dimer assay, Global Registry of
Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI)
risk scores for adverse outcome in patients with non-ST-segment elevation
myocardial infarction (NSTEMI). PATIENTS AND METHODS: A total of 234 patients
(mean age: 57.2+/-11.7 years, 75.2% were males) hospitalized with NSTEMI were
included. Data on D-dimer assay, GRACE and TIMI risk scores were recorded.
Logistic regression analysis was conducted to determine the risk factors
predicting increased mortality. RESULTS: Median D-dimer levels were 349.5 (48.0
7,210.0) ng/mL, the average TIMI score was 3.2+/-1.2 and the GRACE score was
90.4+/-27.6 with high GRACE scores (>118) in 17.5% of patients. The GRACE score
was correlated positively with both the D-dimer assay (r=0.215, P=0.01) and TIMI
scores (r=0.504, P=0.000). Multivariate logistic regression analysis revealed
that higher creatinine levels (odds ratio =18.465, 95% confidence interval: 1.059
322.084, P=0.046) constituted the only significant predictor of increased
mortality risk with no predictive values for age, D-dimer assay, ejection
fraction, glucose, hemoglobin A1c, sodium, albumin or total cholesterol levels
for mortality. CONCLUSION: Serum creatinine levels constituted the sole
independent determinant of mortality risk, with no significant values for D-dimer
assay, GRACE or TIMI scores for predicting the risk of mortality in NSTEMI
patients.
PMID- 28408835
TI - Predictors of common femoral artery access site complications in patients on oral
anticoagulants and undergoing a coronary procedure.
AB - BACKGROUND: It is unclear whether patients on oral anticoagulants (OAC)
undergoing a procedure using common femoral artery access have higher adverse
events when compared to patients who are not anticoagulated at the time of the
procedure. METHODS: We retrospectively reviewed data from consecutive patients
who underwent a cardiac procedure at a tertiary medical center. Patients were
considered (group A) fully or partially anticoagulated if they had an
international normalized ratio (INR) >=1.6 on the day of the procedure or were on
warfarin or new OAC within 48 h and 24 h of the procedure, respectively. The
nonanticoagulated group (group B) had an INR <1.6 or had stopped their warfarin
and new OAC >48 h and >24 h preprocedure, respectively. The index primary end
point of the study was defined as the composite end point of major bleeding,
vascular complications, or cardiovascular-related death during index
hospitalization. The 30-day primary end point was defined as the occurrence of
the index primary end point and up to 30 days postprocedure. RESULTS: A total of
779 patients were included in this study. Of these patients, 27 (3.5%) patients
were in group A. The index primary end point was met in 11/779 (1.4%) patients.
The 30-day primary composite end point was met in 18/779 (2.3%) patients. There
was no difference in the primary end point at index between group A (1/27 [3.7%])
and group B (10/752 [1.3%]; P=0.3155) and no difference in the 30-day primary
composite end point between group A (2/27 [7.4%]) and group B (16/752 [2.1%];
P=0.1313). Multivariable analysis showed that a low creatinine clearance (odds
ratio [OR] =0.56; P=0.0200) and underweight patients (<60 kg; OR =3.94; P=0.0300)
were independent predictors of the 30-day primary composite end point but not
oral anticoagulation (P=0.1500). CONCLUSION: Patients on OAC did not have higher
30-day major adverse events than those who were not anticoagulated at index
procedure.
PMID- 28408836
TI - Drug-related problems in patients with erectile dysfunctions and multiple
comorbidities.
AB - This study was conducted in a tertiary medical center in Kuala Lumpur, Malaysia.
A total of 200 erectile dysfunction (ED) patients with 499 cases who had received
pharmacological treatments for their ED participated in this study. Types, causes
and factors associated with drug-related problems (DRPs) in ED patients with
multiple comorbidities were assessed. A total of 244 DRPs with an average of
1.2+/-2.1 DRPs per patient were identified. Drug interaction contributed the most
to DRPs occurrence. There was a significant higher risk of DRPs in patients with
benign prostatic hyperplasia, lower urinary tract infection and elderly and end
stage renal disease. Early identification of types of DRPs and factors associated
may enhance their prevention and management.
PMID- 28408837
TI - Polymorphisms of VKORC1 and CYP2C9 are associated with warfarin sensitivity in
Chinese population.
AB - OBJECTIVE: Warfarin is a commonly prescribed anticoagulant for prevention of
thromboembolic events. Wide inter-individual dose variation, narrow therapeutic
range and risk of serious bleeding result in difficulties in achieving the
therapeutic effect. The present study was designed to clarify the real biological
significance of the polymorphisms of VKORC1 and cytochrome P450 2C9 (CYP2C9) in
warfarin metabolism. METHODS: A total of 214 patients with warfarin anticoagulant
therapy were selected. During follow-up of anticoagulation, warfarin dosage and
associated international normalized ratio values were recorded. Genetic
polymorphisms of VKORC1 promoter and from exon 1 to exon 3 and CYP2C9 exon 4
sequence were detected by polymerase chain reaction and gene sequencing. RESULTS:
Five polymorphisms were identified in this research, which were VKORC1 1173C>T
(intron 1), 1542G>C (intron 2), 2255C>T (intron 2), 3730C>T (3'-downstream) and
CYP2C9 exon 4 -65G>C. VKORC1 1173CT, 1542GC, 2255CT and 3730CT polymorphisms were
detected in same patients, but CYP2C9 exon 4 -65GC carriers were different from
them. VKORC1 1173CT, 1542GC, 2255CT, 3730CT carriers and CYP2C9 exon 4 -65GC
carriers had significantly higher warfarin daily dosage than others (3.2+/-0.6 vs
3.1+/-1.1 vs 2.6+/-0.8 mg/day). Logistic regression analysis revealed VKORC1
1173CT, 1542GC, 2255CT, 3730CT carrier status (odds ratio [OR] =3.233, 95%
confidence interval [CI]: 1.259-8.303, P=0.015) and obesity with body mass index
>27 kg/m2 (OR =1.223, 95% CI: 1.097-1.363, P<0.001) to have independent and
statistically significant contributions to high warfarin dosage. CONCLUSION: In
general, in VKORC1 1173CT, 1542GC, 2255CT and 3730CT carriers and in obese
patients, warfarin maintenance doses were significantly higher than in the
others.
PMID- 28408839
TI - DNMT1 regulates human endometrial carcinoma cell proliferation.
AB - Endometrial carcinoma (EC) is the most common gynecologic malignancy, but the
molecular events involved in the development and progression of EC remain
unclear. This study aimed to investigate the role of DNA methyltransferase 1
(DNMT1), a member of DNA methyltransferases, in EC. AN3CA cells were transfected
with DNMT1 siRNA. The proliferation, cell cycle, and apoptosis of AN3CA cells
were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The
expression of related genes was detected by polymerase chain reaction and Western
blot analysis. Knockdown of DNMT1 inhibited the proliferation, induced apoptosis,
and G0/G1 phase arrest of AN3CA cells. Furthermore, knockdown of DNMT1
upregulated the expression of nuclear factor kappa-B-inhibitor alpha (NF
kappaBIA) and Bax and downregulated the expression of Bcl-2 and CCND1/2 in AN3CA
cells. In conclusion, this study provides the first evidence that knockdown of
DNMT1 affects the expression of cell cycle- and apoptosis-associated proteins in
EC cells, suggesting the potential of DNMT1 in EC therapy.
PMID- 28408838
TI - DPP-4 inhibitor treatment: beta-cell response but not HbA1c reduction is
dependent on the duration of diabetes.
AB - INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in
patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and
suppressing glucagon secretion. Since T2DM is associated with progressive loss of
beta-cell function, we hypothesized that the DPP-4 inhibitor action to improve
beta-cell function would be attenuated with longer duration of T2DM. METHODS:
Data from six randomized, placebo-controlled trials of 24 weeks duration, where
beta-cell response to vildagliptin 50 mg twice daily was assessed, were pooled.
In each study, the insulin secretory rate relative to glucose (ISR/G 0-2h) during
glucose load (standard meal or oral glucose tolerance test) was assessed at
baseline and end of study. The mean placebo-subtracted difference (PSD) in the
change in ISR/G 0-2h from baseline for each study was evaluated as a function of
age, duration of T2DM, baseline ISR/G 0-2h, glycated hemoglobin (HbA1c), fasting
plasma glucose, body mass index, and mean PSD in the change in HbA1c from
baseline, using univariate model. RESULTS: There was a strong negative
association between the PSD in the change from baseline in ISR/G 0-2h and
duration of T2DM (r= -0.89, p<0.02). However, there was no association between
the PSD in the change from baseline in ISR/G 0-2h and the PSD in the change from
baseline in HbA1c (r=0.33, p=0.52). None of the other characteristics were
significantly associated with mean PSD change in ISR/G 0-2h. CONCLUSION: These
findings indicate that the response of the beta-cell, but not the HbA1c
reduction, with vildagliptin is dependent on duration of T2DM. Further, it can be
speculated that glucagon suppression may become the predominant mechanism via
which glycemic control is improved when treatment with a DPP-4 inhibitor, such as
vildagliptin, is initiated late in the natural course of T2DM.
PMID- 28408840
TI - Clinical course and outcome of patients with high-level microsatellite
instability cancers in a real-life setting: a retrospective analysis.
AB - BACKGROUND: The prognostic and predictive significance of the high-level
microsatellite instability (MSI-H) phenotype in various malignancies is unclear.
We describe the characteristics, clinical course, and outcomes of patients with
MSI-H malignancies treated in a real-life hospital setting. PATIENTS AND METHODS:
A retrospective analysis of MSI-H cancer patient files was conducted. We analyzed
the genetic data, clinical characteristics, and oncological treatments, including
chemotherapy and surgical interventions. RESULTS: Clinical data of 73 MSI-H
cancer patients were available. Mean age at diagnosis of first malignancy was
52.3 years. Eight patients (11%) had more than four malignancies each. Most
patients (76%) had colorectal cancer (CRC). Seventeen patients (23%) had only
extracolonic malignancies. Eighteen women (36%) had gynecological malignancy.
Nine women (18%) had breast cancer. Mean follow-up was 8.5 years. Five-year
overall survival and disease-free survival of all MSI-H cancer patients from
first malignancy were 86% and 74.6%, respectively. Five-year overall survival
rates of stage 2, 3, and 4 MSI-H CRC patients were 89.5%, 58.4%, and 22.9%,
respectively. CONCLUSION: Although the overall prognosis of MSI-H cancer patients
is favorable, this advantage may not be maintained in advanced MSI-H CRC
patients.
PMID- 28408842
TI - Spotlight on ibrutinib and its potential in frontline treatment of chronic
lymphocytic leukemia.
AB - Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the adult
population. Current efforts are focused on better understanding the intricate
pathophysiology of the disease to develop successful targeted therapies.
Ibrutinib is emerging as an important agent in this new age of targeted treatment
for CLL. As a Bruton's tyrosine kinase inhibitor, it blocks the signaling pathway
that malignant B-lymphocytes need for growth and maturation. Ibrutinib's role in
therapy was further expanded recently when the US Food and Drug Administration
approved its use in both frontline and salvage treatment for patients with CLL.
This review assesses the effectiveness of ibrutinib in the frontline setting, its
efficacy in various types of patients with CLL, and its safety and tolerability.
PMID- 28408841
TI - Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells
immunotherapy for the treatment of esophageal cancer in China: a meta-analysis.
AB - BACKGROUND: Immunotherapy based on cytokine-induced killer cells or combination
of dendritic cells and cytokine-induced killer cells (CIK/DC-CIK) showed
promising clinical outcomes for treating esophageal cancer (EC). However, the
clinical benefit varies among previous studies. Therefore, it is necessary to
systematically evaluate the curative efficacy and safety of CIK/DC-CIK
immunotherapy as an adjuvant therapy for conventional therapeutic strategies in
the treatment of EC. MATERIALS AND METHODS: Clinical trials published before
October 2016 and reporting CIK/DC-CIK immunotherapy treatment responses or safety
for EC were searched in Cochrane Library, EMBASE, PubMed, Wanfang and China
National Knowledge Internet databases. Research quality and heterogeneity were
evaluated before analysis, and pooled analyses were performed using random- or
fixed-effect models. RESULTS: This research covered 11 trials including 994 EC
patients. Results of this meta-analysis indicated that compared with conventional
therapy, the combination of conventional therapy with CIK/DC-CIK immunotherapy
significantly prolonged the 1-year overall survival (OS) rate, overall response
rate (ORR) and disease control rate (DCR) (1-year OS: P=0.0005; ORR and DCR:
P<0.00001). Patients with combination therapy also showed significantly improved
quality of life (QoL) (P=0.02). After CIK/DC-CIK immunotherapy, lymphocyte
percentages of CD3+ and CD3-CD56+ subsets (P<0.01) and cytokines levels of IFN
gamma, -2, TNF-alpha and IL-12 (P<0.00001) were significantly increased, and the
percentage of cluster of differentiation (CD)4+CD25+CD127- subset was
significantly decreased, whereas analysis of CD4+, CD8+, CD4+/CD8+ and CD3+CD56+
did not show significant difference (P>0.05). CONCLUSION: The combination of
CIK/DC-CIK immunotherapy and conventional therapy is safe and markedly prolongs
survival time, enhances immune function and improves the treatment efficacy for
EC.
PMID- 28408843
TI - Expression of SHP-1 and SOCS6 in patients with acute leukemia and their clinical
implication.
AB - BACKGROUND: To investigate the expression and clinical relevance of Src homology
region 2 domain-containing phosphatase-1 (SHP-1) and suppressor of cytokine
signaling 6 (SOCS6) in acute leukemia (AL). PATIENTS AND METHODS: The enrolled AL
patients were divided into three groups (newly diagnosed, relapsed, and complete
remission [CR]). Healthy donors were also included as a control group in this
study. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR)
was performed to measure messenger RNA (mRNA) expression of SHP-1 and SOCS6.
Statistical analysis was conducted to analyze the correlation between mRNA levels
of SHP-1 and SOCS6 with patient outcomes. RESULTS: mRNA expression of SHP-1 was
significantly lower in AL patients than that in healthy donors. The newly
diagnosed or relapsed AL patients had lower mRNA levels of SHP-1 than the
patients in CR. In contrast, SOCS6 mRNA expression was significantly higher in
newly diagnosed or relapsed patients than that in patients in CR as well as
healthy donors. However, mRNA levels of both SHP-1 and SOCS6 were positively
correlated with the patient remission. The chemotherapy-induced remission rate
was higher in patients with detectable SHP-1 or SOCS6 expression than in patients
with undetectable SHP-1 or SOCS6 expression. Furthermore, the AL patients with
detectable SHP-1 mRNA expression had lower incidence rate of invasive fungal
infection. CONCLUSION: The results suggest that expression patterns of SHP-1 and
SOCS6 differ in AL patients. Despite the difference, expression of SHP-1 and
SOCS6 is associated with favorable outcomes, suggesting an anticancer property of
these two genes in AL.
PMID- 28408844
TI - Non-small-cell lung cancer cell lines A549 and NCI-H460 express hypoxanthine
guanine phosphoribosyltransferase on the plasma membrane.
AB - In both males and females, lung cancer is one of the most lethal cancers
worldwide and accounts for >30% of cancer-related deaths. Despite advances in
biomarker analysis and tumor characterization, there remains a need to find
suitable biomarker antigen targets for treatment in late-stage lung cancer.
Previous research on the salvage pathway enzyme TK1 shows a unique relationship
with cancer patients as serum levels are raised according to cancer grade. To
expand this analysis, the other salvage pathway enzymes were evaluated for
possible upregulation within lung cancer. Adenine phosphoribosyltransferase,
deoxycytidine kinase, and hypoxanthine guanine phosphoribosyltransferase (HPRT)
were assessed for their presentation on two non-small-cell lung cancer cell lines
NCI-H460 and A549. In the present study, we show that deoxycytidine kinase and
adenine phosphoribosyltransferase have no significant relationship with the
membrane of NCI-H460 cells. However, we found significant localization of HPRT to
the membrane of NCI-H460 and A549 cells. When treated with anti-HPRT antibodies,
the average fluorescence of the cell population increased by 24.3% and 12.9% in
NCI-H460 and A549 cells, respectively, in comparison with controls. To ensure
that expression was not attributed to cytoplasmic HPRT, confocal microscopy was
performed to visualize HPRT binding on the plasma membrane. After staining NCI
H460 cells treated with both fluorescent antibodies and a membrane-specific dye,
we observed direct overlap between HPRT and the membrane of the cancer cells.
Additionally, gold-conjugated antibodies were used to label and quantify the
amount of HPRT on the cell surface using scanning electron microscopy and energy
dispersive analysis X-ray. Further confirming HPRT presence, the gold weight
percentage of the sample increased significantly when NCI-H460 cells were exposed
to HPRT antibody (P=0.012) in comparison with isotype controls. Our results show
that HPRT is localized on the surface of these non-small-cell lung cancer cell
lines.
PMID- 28408845
TI - FAM172A expression in circulating tumor cells for prediction of high-risk
subgroups of colorectal cancer.
AB - OBJECTIVES: Previous studies used enumerated circulating tumor cells (CTCs) to
predict prognosis and therapeutic effect in several types of cancers. However,
increasing evidence showed that only enumerated CTCs were not enough to reflect
the heterogeneity of tumors. Therefore, we classified different metastasis
potentials of CTCs from colorectal cancer (CRC) patients to improve the accuracy
of prognosis by CTCs. METHODS: Blood samples were collected from 45 primary CRC
patients. CTCs were enriched by blood filtration, and the RNA in situ
hybridization method was used to identify and discriminate subgroups of CTCs.
Later, FAM172A expression in individual CTCs was measured. RESULTS: Three CTC
subgroups (epithelial/biophenotypic/mesenchymal CTCs) were identified using
epithelial-mesenchymal transition markers. In our research, mesenchymal CTCs
significantly increased along with tumor progression, including developing
distant metastasis and vascular invasion. Furthermore, FAM172A expression rate in
mesenchymal CTCs was significantly higher than that in epithelial CTCs, which
suggested that FAM172A may correlate with tumor malignancy. This hypothesis was
further verified by FAM172A expression in mesenchymal CTCs strictly related to
tumor aggressiveness factors. Finally, we revealed that mesenchymal CTCs and
FAM172A expression may predict high-risk subgroups in stage II CRC. CONCLUSION:
Our research proved that CTCs could serve as feasible surrogate samples to detect
gene expression as a predictive biomarker for tumor evaluation.
PMID- 28408846
TI - Apoptotic and genomic effects of corilagin on SKOV3 ovarian cancer cell line.
AB - Corilagin is a member of the tannin family and has been isolated from traditional
Chinese medicinal plants, such as Phyllanthus spp. Corilagin has anti
inflammatory, antioxidative, antiatherogenic, and antihypertensive effects in
various experimental models. In this research, we aimed to investigate for the
first time whether corilagin had apoptotic and genomic effects in ovarian cancer
treatment in the same study. The potential apoptotic of corilagin was
investigated using a WST1 cell proliferation test, caspase 3, and mitochondrial
membrane potential JC1 assays in a time- and dose-dependent manner. Genomic
changes in expression levels against corilagin treatment were measured using an
Illumina human HT-12V4 BeadChip microarray. Bioinformatic data analyses were
performed using GenomeStudio and Ingenuity Pathway Analysis software. The data of
our study demonstrated that there were statistically significant time- and dose
dependent increases in caspase 3 enzymatic activity and loss of mitochondrial
membrane potential in line with decreases in cancer cell proliferation. According
to gene-ontology analysis, we found that adherens junctions, antigen processing
and presentation, and the phosphatidylinositol signaling system were the most
statistically significant networks in response to corilagin treatment on SKOV3
cells, in a time- and dose-dependent manner. The apoptotic and genome-wide
effects of corilagin on ovarian cancer cells were examined in detail for the
first time in the literature. The results of our study suggest that corilagin
might have the potential to be used as a new treatment option for epithelial
ovarian cancer.
PMID- 28408847
TI - Cost analysis of pulmonary lobectomy procedure: comparison of stapler versus
precision dissection and sealant.
AB - OBJECTIVE: We aimed to evaluate the direct costs of pulmonary lobectomy
hospitalization, comparing surgical techniques for the division of interlobar
fissures: stapler (ST) versus electrocautery and hemostatic sealant patch (ES).
METHODS: The cost comparison analysis was based on the clinical pathway and drawn
up by collecting the information available from the Thoracic Surgery Division
medical team at Mantova Hospital. Direct resource consumption was derived from a
previous randomized controlled trial including 40 patients. Use and maintenance
of technology, equipment and operating room; administrative plus general costs;
and 30-day use of postsurgery hospital resources were considered. The analysis
was conducted from the hospital perspective. RESULTS: On the average, a patient
submitted to pulmonary lobectomy costs ?9,744.29. This sum could vary from ?9,027
(using ES) to ?10,460 (using ST). The overall lower incidence (50% vs 95%,
P=0.0001) and duration of air leakage (1.7 days vs 4.5 days, P=0.0001) in the ES
group significantly affects the mean time of hospital stay (11.0 days vs 14.3
days) and costs. Cost saving in the ES group was also driven by the lower
incidence of complications. The main key cost driver was staff employment (42%),
then consumables (34%) and operating room costs (12%). CONCLUSION: There is an
overall saving of around ?1,432.90 when using ES patch for each pulmonary
lobectomy. Among patients undergoing this surgical procedure, ES can
significantly reduce air leakage incidence and duration, as well as decrease
hospitalization rates. However, further multicenter research should be developed
considering different clinical and managerial settings.
PMID- 28408848
TI - Ingenol mebutate in low amounts for the treatment of actinic keratosis in Korean
patients.
AB - BACKGROUND: Ingenol mebutate (IM), a novel agent for field therapy of actinic
keratosis (AK), has a drawback of inducing local skin reactions (LSRs), which may
cause discomfort in patients. To reduce the LSRs, we tried the application of IM
in low amounts. OBJECTIVE: The purpose of this study was to review Korean
patients with AK being treated with IM and evaluate the LSRs and therapeutic
outcomes of low amounts of IM. METHODS: We retrospectively reviewed 47 patients
with AK on the face. A total of 20 and 27 patients were treated by applying
recommended amount of 18.8 mg/cm2 and the lower amount of 10 mg/cm2,
respectively. RESULTS: The mean composite LSR score for the low amount group
(LAG; 12.18+/-3.29) was significantly lower than that for the recommended amount
group (RAG; 15.45+/-2.70) (P<0.01, independent sample t-test). The 2-month
clearance rate calculated by the number of AKs before and after treatment in each
patient was significantly higher for RAG (88.16%), compared with 75.56% for LAG
(P<0.001). CONCLUSION: Low amount of IM for the treatment of facial AK
significantly reduced LSRs in Korean patients. Minimizing LSRs may allow for a
secondary targeting treatment of IM for the residual lesions, depending on
initial treatment outcomes.
PMID- 28408849
TI - A retrospective epidemiological study of skin diseases among pediatric population
attending a tertiary dermatology referral center in Northern Greece.
AB - BACKGROUND: The incidence of skin diseases in children is influenced by
hereditary, social, and environmental factors. The objective of this study was to
determine the incidence of pediatric dermatoses at a University Hospital in
Northern Greece. PATIENTS AND METHODS: We reviewed epidemiologic data of 940
patients, aged 0-18 years, who were referred to the outpatient clinic of a
University Hospital between January 2013 and December 2015. Demographic data and
the frequency of the various diagnoses in various age groups were studied.
RESULTS: Nine hundred and forty children and adolescents with 1020 diagnoses were
included in the study (52.8% females and 47.2% males). The 10 most frequent
diagnoses were: dermatitis/eczema (31.5%), viral infections (12.5%), pigmentary
disorders (7.4%), melanocytic nevi (5.8%), alopecia areata (5.8%), acne (5.6%),
nail disorders (3.3%), vascular malformations and hemangiomas (2.9%), psoriasis
(2.6%), and bacterial infections (2.6%). Atopic dermatitis was the most prevalent
dermatosis in all age groups accounting for a total of 20.9% of the study
population. A remarkably high incidence of various forms of mastocytosis (2.2%)
was seen in our data. CONCLUSION: Atopic dermatitis is the most frequent
pediatric dermatosis in all age groups. Viral infections, pigmentary disorders,
and nevi account for a significant proportion of the referrals. The high
incidence of mastocytosis in our study may be attributed to overdiagnosis,
overestimation due to the relatively small study population, or it may represent
the real incidence of mastocytosis in our region. The low incidence of acne in
our study may be attributed to the fact that only severe cases are referred to
our hospital.
PMID- 28408850
TI - Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic
biliary drainage after failed endoscopic retrograde cholangiopancreatography: a
meta-analysis.
AB - The failure rate of endoscopic retrograde cholangiopancreatography for biliary
cannulation is approximately 6%-7% in cases of obstructive jaundice. Percutaneous
transhepatic biliary drainage (PTBD) is the procedure of choice in such cases.
Endoscopic ultrasound-guided biliary drainage (EGBD) is a novel technique that
allows biliary drainage by echoendoscopy and fluoroscopy using a stent from the
biliary tree to the gastrointestinal tract. Information in PubMed, Scopus,
clinicaltrials.gov and Cochrane review were analyzed to obtain studies comparing
EGBD and PTBD. Six studies fulfilled the inclusion criteria. Technical (odds
ratio (OR): 0.34; confidence interval (CI) 0.10-1.14; p=0.05) and clinical (OR:
1.48; CI 0.46-4.79; p=0.51) success rates were not statistically significant
between the EGBD and PTBD groups. Mild adverse events were nonsignificantly
different (OR: 0.36; CI 0.10-1.24; p=0.11) but not the moderate-to-severe adverse
events (OR: 0.16; CI 0.08-0.32; p<=0.00001) and total adverse events (OR: 0.34;
CI 0.20-0.59; p<=0.0001). EGBD is equally effective but safer than PTBD.
PMID- 28408851
TI - Prilocaine hydrochloride 2% hyperbaric solution for intrathecal injection: a
clinical review.
AB - Prilocaine is a local anesthetic characterized by intermediate potency and
duration and fast onset of action. As hyperbaric formulation of 5% solution, it
was introduced and has been successfully used for spinal anesthesia since 1960. A
new formulation of 2% plain and hyperbaric solution is currently available in
Europe. Because of its lower incidence of transient neurological symptoms,
prilocaine is suggested as substitute to lidocaine and mepivacaine in spinal
anesthesia for ambulatory surgery, as well as a suitable alternative to low doses
of long-acting local anesthetics. The National Library of Medicine database, the
Excerpta Medica database, the Cochrane Database of Systematic Reviews, and the
Cochrane Central Register of Controlled Trials database, were searched for the
period 1970 to September 2016, with the aim to identify studies evaluating the
intrathecal use of 2% prilocaine. A total of 13 randomized clinical trials
(RCTs), 1 observational study, 2 dose finding, and 4 systematic reviews has been
used for this review. The studies evaluated showed that 2% hyperbaric prilocaine
due to a favorable anesthetic and safety profile is an alternative drug to
lidocaine and mepivacaine for spinal anesthesia of intermediate or short
duration. In comparison with plain solutions, hyperbaricity remarkably
accelerates the onset and offset times of intrathecal 2% prilocaine. Literature
suggests a dose ranging between 40 and 60 mg of prilocaine for lower extremities
and lower abdominal procedures lasting up to 90 min, whereas a dose ranging from
10 to 30 mg is appropriate for perineal surgery. Readiness for discharge occurs
in ~4 h from spinal administration.
PMID- 28408852
TI - The role of the chemokine receptor XCR1 in breast cancer cells.
AB - Considerable attention has recently been paid to the application of chemokines to
cancer immunotherapy due to their complex role in cell proliferation, invasion,
metastasis, and tumorigenesis, which extends beyond the regulation of lymphocyte
migration during immune responses. The expression and the function of the
chemokine receptor XCR1 on breast cancer have remained elusive to date. In this
study, the expressions of XCR1 mRNA were tested by quantitative real-time
polymerase chain reaction in one breast epithelial cell line (MCF-10A) and nine
breast cancer cell lines (MDA-MB-231, 231HM, 231BO, MDA-MB-468, MCF-7, T47D, Bcap
37, ZR-75-30, and SK-BR-3). We established XCR1-overexpressing breast cancer cell
line MDA-MB-231 (231/XCR1) in XCR1 low expression cell line MDA-MB-231 (231). The
ability of proliferation, invasion, and metastasis was measured by CCK8, plate
cloning formation, and transwell analysis, respectively, in XCR1-overexpressing
breast cancer cell lines (231/XCR1) and their parental cell line MDA-MB
231/Vector (simplified as "231/Vector"); 5*106/100 MUL cells were inoculated in
mammary fat pad of BALB/c nude mice. There were six BALB/c nude mice in the
experimental group and control group. Protein expression was analyzed by cell
immunofluorescence and Western blot. The growth of XCR1-overexpressing human
breast cancer cell line MDA-MB-231 in vitro was restrained and tumorigenesis in
vivo was also extenuated, its mechanism may involve in the inhibition of MAPK and
PI3K/AKT/mTOR signaling pathway, but increase in LC3 expression. However, the
overexpression of XCR1 in human breast cancer cell line MDA-MB-231 in vitro can
promote the migration and invasion partially due to decreasing the protein level
of beta-catenin. Therefore, XCR1 can affect the biological characteristics of
some special breast cancer cells through complex signal transduction pathway.
PMID- 28408853
TI - Tumescent mastectomy: the current indications and operative tips and tricks.
AB - BACKGROUND: Tumescent mastectomy refers to usage of a mixture of lidocaine and
epinephrine in a diluting saline solution that makes flaps firm and tense, thus
minimizing systemic drugs toxicity and making surgery possible with minimal
bleeding. This technique is very useful in elder women and those with American
Society of Anesthesiologists; score III and IV. The objective was to establish an
alternative safe technique to general anesthesia in some selected mastectomy
patients. PATIENTS AND METHODS: Twenty candidate women for total mastectomy and
axillary dissection were enrolled and consented to participate. After
preparation, an anatomically directed infiltration was made under sedation, using
a cocktail of lidocaine, bupivacaine, and epinephrine, followed after 20 minutes
by the surgical incision and completion of mastectomy. All intraoperative and
postoperative outcomes were recorded. RESULTS: Although 7 cases required added
analgesic medications, no conversion for general anesthesia was recorded. Mean
operative time was 81+/-15.8 minutes. Mean blood loss was 95.8+/-47.5 mL. There
was no recorded intraoperative hemodynamic instability. Postoperative visual
analog score was not exceeding 4 till the end of the first 24 hours. Opioids were
not required in any case, and the mean dosage of Ketorolac used was 30+/-8.75 mg.
Drains output and the incidence of postoperative complications were acceptable.
CONCLUSION: We can consider tumescent mastectomy in well-selected patients a safe
alternative for performing mastectomy when general anesthesia is hazardous, with
minimal blood loss and long lasting postoperative analgesia without an additive
effect on the operative time, hospital stay, and intraoperative and postoperative
complications.
PMID- 28408854
TI - Control of confounding in the analysis phase - an overview for clinicians.
AB - In observational studies, control of confounding can be done in the design and
analysis phases. Using examples from large health care database studies, this
article provides the clinicians with an overview of standard methods in the
analysis phase, such as stratification, standardization, multivariable regression
analysis and propensity score (PS) methods, together with the more advanced high
dimensional propensity score (HD-PS) method. We describe the progression from
simple stratification confined to the inclusion of a few potential confounders to
complex modeling procedures such as the HD-PS approach by which hundreds of
potential confounders are extracted from large health care databases.
Stratification and standardization assist in the understanding of the data at a
detailed level, while accounting for potential confounders. Incorporating several
potential confounders in the analysis typically implies the choice between
multivariable analysis and PS methods. Although PS methods have gained remarkable
popularity in recent years, there is an ongoing discussion on the advantages and
disadvantages of PS methods as compared to those of multivariable analysis.
Furthermore, the HD-PS method, despite its generous inclusion of potential
confounders, is also associated with potential pitfalls. All methods are
dependent on the assumption of no unknown, unmeasured and residual confounding
and suffer from the difficulty of identifying true confounders. Even in large
health care databases, insufficient or poor data may contribute to these
challenges. The trend in data collection is to compile more fine-grained data on
lifestyle and severity of diseases, based on self-reporting and modern
technologies. This will surely improve our ability to incorporate relevant
confounders or their proxies. However, despite a remarkable development of
methods that account for confounding and new data opportunities, confounding will
remain a serious issue. Considering the advantages and disadvantages of different
methods, we emphasize the importance of the clinical input and of the interplay
between clinicians and analysts to ensure a proper analysis.
PMID- 28408856
TI - Writing skills enhancement for public health professionals in Rwanda.
AB - In 2013, Canadian scholars delivered a 1-week workshop to 30 junior public health
professionals in Rwanda. The goal was to improve the Rwandans' skills and
confidence with respect to writing scientific papers for submission to
international peer-reviewed global health journals. As a result of the workshop,
there was a statistically significant improvement in participants' reported
confidence in many aspects of navigating the publishing process, but no
improvement in confidence regarding statistically analyzing their data.
Remarkably, as a group, participants were able to write an article for a leading
international journal, which was subsequently published. Results indicate that
similar interventions would be both successful and well received, especially if
targeted to individuals at a similar stage of career progress.
PMID- 28408855
TI - Targeted therapy for soft tissue sarcomas in adolescents and young adults.
AB - Soft tissue sarcomas (STSs) are a heterogeneous group of tumors originating from
the mesenchyme. Even though they affect individuals in all age groups, the
prevalence of subtypes of STSs changes significantly from childhood through
adolescence into adulthood. The mainstay of therapy is surgery, with or without
the addition of chemotherapy and/or radiation therapy. These treatment modalities
are associated, in many cases, with significant morbidity and, given the
heterogeneity of tumor histologies encompassed by the term "STS", have not
uniformly improved outcomes. Moreover, some subgroups of STSs appear to be more,
and others less, responsive to conventional chemotherapy agents. Over the last
two decades, our understanding of the biology of STSs is slowly increasing,
allowing for the development of more targeted therapies. We review the new
treatment modalities that have been tested on patients with STSs, with a special
focus on adolescents and young adults, a group of patients that is often
underrepresented in clinical trials and has not received the dedicated attention
it deserves, given the significant differences in biology and treatment response
in comparison to children and adults.
PMID- 28408858
TI - EPPS16: nuclear parton distributions with LHC data.
AB - We introduce a global analysis of collinearly factorized nuclear parton
distribution functions (PDFs) including, for the first time, data constraints
from LHC proton-lead collisions. In comparison to our previous analysis, EPS09,
where data only from charged-lepton-nucleus deep inelastic scattering (DIS),
Drell-Yan (DY) dilepton production in proton-nucleus collisions and inclusive
pion production in deuteron-nucleus collisions were the input, we now increase
the variety of data constraints to cover also neutrino-nucleus DIS and low-mass
DY production in pion-nucleus collisions. The new LHC data significantly extend
the kinematic reach of the data constraints. We now allow much more freedom for
the flavor dependence of nuclear effects than in other currently available
analyses. As a result, especially the uncertainty estimates are more objective
flavor by flavor. The neutrino DIS plays a pivotal role in obtaining a mutually
consistent behavior for both up and down valence quarks, and the LHC dijet data
clearly constrain gluons at large momentum fraction. Mainly for insufficient
statistics, the pion-nucleus DY and heavy-gauge-boson production in proton-lead
collisions impose less visible constraints. The outcome - a new set of next-to
leading order nuclear PDFs called EPPS16 - is made available for applications in
high-energy nuclear collisions.
PMID- 28408860
TI - Is imperfection becoming easier to live with for doctors?
AB - OBJECTIVE: Being involved in serious patient injury is devastating for most
doctors. During the last two decades, several efforts have been launched to
improve Norwegian doctors' coping with adverse events and complaints. METHODS:
The method involved survey to a representative sample of 1792 Norwegian doctors
in 2012. The questions on adverse events and its effects were previously asked in
2000. RESULTS: Response rate was 71%. More doctors reported to have been involved
in episodes with serious patient harm in 2012 (35%) than in 2000 (28%), and more
of the episodes were reported as required by law. Doctors below age 50 report
better support from colleagues, more collegial retrospective discussion on the
event and less patient/family blame. In all, 27% of the doctors had been reported
to the Norwegian Board of Health Supervision; 79% of these complaints were
rejected; 73% of the doctors who had received a reaction from the health
authorities found the reaction reasonable, but almost one out of five practiced
more testing and referrals after a complaint and 25% claimed that the complaint
had made them into a more fearful doctor. CONCLUSION: Our results indicate that
adverse events are being met more openly in 2012 than in 2000, and that coping
with imperfection and patient complaints is less devastating for new generations
of doctors.
PMID- 28408862
TI - Obesity Stigma and Bias.
AB - Overweight and obesity are escalating in epidemic proportions in the United
States. Individuals with overweight and obesity are often reluctant to seek
medical help, not only for weight reduction but also for any health issue because
of perceived provider discrimination. Providers who are biased against
individuals with obesity can hinder our nation's effort to effectively fight the
obesity epidemic. By addressing weight bias in the provider setting, individuals
affected by obesity may be more likely to engage in a meaningful and productive
discussion of weight. Providers need to be the go-to source for obesity-focused
information on new and emerging treatments.
PMID- 28408861
TI - Heart disease risk and self-efficacy in overweight and obese adults.
PMID- 28408863
TI - Experimental system design for the integration of trapped-ion and superconducting
qubit systems.
AB - We present a design for the experimental integration of ion trapping and
superconducting qubit systems as a step towards the realization of a quantum
hybrid system. The scheme addresses two key difficulties in realizing such a
system: a combined microfabricated ion trap and superconducting qubit
architecture, and the experimental infrastructure to facilitate both
technologies. Developing upon work by Kielpinski et al. (Phys Rev Lett
108(13):130504, 2012. doi:10.1103/PhysRevLett.108.130504), we describe the
design, simulation and fabrication process for a microfabricated ion trap capable
of coupling an ion to a superconducting microwave LC circuit with a coupling
strength in the tens of kHz. We also describe existing difficulties in combining
the experimental infrastructure of an ion trapping set-up into a dilution
refrigerator with superconducting qubits and present solutions that can be
immediately implemented using current technology.
PMID- 28408864
TI - Repeated Listening Increases the Liking for Music Regardless of Its Complexity:
Implications for the Appreciation and Aesthetics of Music.
AB - Psychological and aesthetic theories predict that music is appreciated at
optimal, peak levels of familiarity and complexity, and that appreciation of
music exhibits an inverted U-shaped relationship with familiarity as well as
complexity. Because increased familiarity conceivably leads to improved
processing and less perceived complexity, we test whether there is an interaction
between familiarity and complexity. Specifically, increased familiarity should
render the music subjectively less complex, and therefore move the apex of the U
curve toward greater complexity. A naturalistic listening experiment was
conducted, featuring 40 music examples (ME) divided by experts into 4 levels of
complexity prior to the main experiment. The MEs were presented 28 times each
across a period of approximately 4 weeks, and individual ratings were assessed
throughout the experiment. Ratings of liking increased monotonically with
repeated listening at all levels of complexity; both the simplest and the most
complex MEs were liked more as a function of listening time, without any
indication of a U-shaped relation. Although the MEs were previously unknown to
the participants, the strongest predictor of liking was familiarity in terms of
having listened to similar music before, i.e., familiarity with musical style. We
conclude that familiarity is the single most important variable for explaining
differences in liking among music, regardless of the complexity of the music.
PMID- 28408865
TI - Tau Pathology Distribution in Alzheimer's disease Corresponds Differentially to
Cognition-Relevant Functional Brain Networks.
AB - Neuropathological studies have shown that the typical neurofibrillary pathology
of hyperphosphorylated tau protein in Alzheimer's disease (AD) preferentially
affects specific brain regions whereas others remain relatively spared. It has
been suggested that the distinct regional distribution profile of tau pathology
in AD may be a consequence of the intrinsic network structure of the human brain.
The spatially distributed brain regions that are most affected by the spread of
tau pathology may hence reflect an interconnected neuronal system. Here, we
characterized the brain-wide regional distribution profile of tau pathology in AD
using 18F-AV 1451 tau-sensitive positron emission tomography (PET) imaging, and
studied this pattern in relation to the functional network organization of the
human brain. Specifically, we quantified the spatial correspondence of the
regional distribution pattern of PET-evidenced tau pathology in AD with
functional brain networks characterized by large-scale resting state functional
magnetic resonance imaging (rs-fMRI) data in healthy subjects. Regional
distribution patterns of increased PET-evidenced tau pathology in AD compared to
controls were characterized in two independent samples of prodromal and manifest
AD cases (the Swedish BioFINDER study, n = 44; the ADNI study, n = 35). In the
BioFINDER study we found that the typical AD tau pattern involved predominantly
inferior, medial, and lateral temporal cortical areas, as well as the
precuneus/posterior cingulate, and lateral parts of the parietal and occipital
cortex. This pattern overlapped primarily with the dorsal attention, and to some
extent with higher visual, limbic and parts of the default-mode network. PET
evidenced tau pathology in the ADNI replication sample, which represented a more
prodromal group of AD cases, was less pronounced but showed a highly similar
spatial distribution profile, suggesting an earlier-stage snapshot of a
consistently progressing regional pattern. In conclusion, the present study
indicates that the regional deposition of tau aggregates in AD predominantly
affects higher-order cognitive over primary sensory-motor networks, but does not
appear to be specific for the default-mode or related limbic networks.
PMID- 28408867
TI - Visualization of SNARE-Mediated Hemifusion between Giant Unilamellar Vesicles
Arrested by Myricetin.
AB - Neurotransmitters are released within a millisecond after Ca2+ arrives at an
active zone. However, the vesicle fusion pathway underlying this synchronous
release is yet to be understood. At the center of controversy is whether
hemifusion, in which outer leaflets are merged while inner leaflets are still
separated, is an on-pathway or off-pathway product of Ca2+-triggered exocytosis.
Using the single vesicle fusion assay, we recently demonstrated that hemifusion
is an on-pathway intermediate that immediately proceeds to full fusion upon Ca2+
triggering. It has been shown that the flavonoid myricetin arrests soluble N
ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE)
mediated vesicle fusion at hemifusion, but that the hemifused vesicles
spontaneously convert to full fusion when the myricetin clamp is removed by the
enzyme laccase. In the present study, we visualized SNARE-mediated hemifusion
between two SNARE-reconstituted giant unilamellar vesicles (GUVs) arrested by
myricetin. The large size of the GUVs enabled us to directly image the hemifusion
between them. When two merging GUVs were labeled with different fluorescent dyes,
GUV pairs showed asymmetric fluorescence intensities depending on the position on
the GUV pair consistent with what is expected for hemifusion. The flow of lipids
from one vesicle to the other was revealed with fluorescence recovery after
photobleaching (FRAP), indicating that the two membranes had hemifused. These
results support the hypothesis that hemifusion may be the molecular status that
primes Ca2+-triggered millisecond exocytosis. This study represents the first
imaging of SNARE-driven hemifusion between GUVs.
PMID- 28408866
TI - Post-translational Modifications and Protein Quality Control in Motor Neuron and
Polyglutamine Diseases.
AB - Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ)
diseases, are a broad class of neurological disorders. These diseases are
characterized by neuronal dysfunction and death, and by the accumulation of toxic
aggregation-prone proteins in the forms of inclusions and micro-aggregates.
Protein quality control is a cellular mechanism to reduce the burden of
accumulation of misfolded proteins, a function that results from the coordinated
actions of chaperones and degradation systems, such as the ubiquitin-proteasome
system (UPS) and autophagy-lysosomal degradation system. The rate of turnover,
aggregation and degradation of the disease-causing proteins is modulated by post
translational modifications (PTMs), such as phosphorylation, arginine
methylation, palmitoylation, acetylation, SUMOylation, ubiquitination, and
proteolytic cleavage. Here, we describe how PTMs of proteins linked to motor
neuron and polyQ diseases can either enhance or suppress protein quality control
check and protein aggregation and degradation. The identification of molecular
strategies targeting these modifications may offer novel avenues for the
treatment of these yet incurable diseases.
PMID- 28408868
TI - Perivascular Accumulation of beta-Sheet-Rich Proteins in Offspring Brain
following Maternal Exposure to Carbon Black Nanoparticles.
AB - Environmental stimulation during brain development is an important risk factor
for the development of neurodegenerative disease. Clinical evidence indicates
that prenatal exposure to particulate air pollutants leads to diffuse damage to
the neurovascular unit in the developing brain and accelerates neurodegeneration.
Maternal exposure to carbon black nanoparticles (CB-NPs), used as a model for
particulate air pollution, induces long-lasting diffuse perivascular
abnormalities. We aimed to comprehensively characterize the perivascular
abnormalities related to maternal NPs exposure using Fourier transform infrared
microspectroscopy (in situ FT-IR) and classical staining analysis. Pregnant ICR
mice were intranasally treated with a CB-NPs suspension (95 MUg/kg at a time) on
gestational days 5 and 9. Brains were collected 6 weeks after birth and sliced to
prepare 10-MUm-thick serial sections. Reflective spectra of in situ FT-IR were
acquired using lattice measurements (x-axis: 7, y-axis: 7, 30-MUm apertures)
around a centered blood vessel. We also performed mapping analysis of protein
secondary structures. Serial sections were stained with using periodic acid
Schiff or immunofluorescence to examine the phenotypes of the perivascular areas.
Peaks of amide I bands in spectra from perivascular areas were shifted by
maternal NPs exposure. However, there were two types of peak-shift in one mouse
in the exposure group. Some vessels had a large peak-shift and others had a small
peak-shift. In situ FT-IR combined with traditional staining revealed that the
large peak-shift was induced around blood vessel adjacent to astrocytes with
glial fibrillary acidic protein and aquaporin-4 over-expression and perivascular
macrophages (PVMs) with enlarged lysosome granules. Furthermore, protein
secondary structural analysis indicated that maternal NPs exposure led to
increases in beta-sheet content and decreases in alpha-helix content in areas
that are mostly close to the centered blood vessel displaying histopathological
changes. These results suggest that beta-sheet-rich waste proteins, which are
denatured by maternal NPs exposure, likely accumulate in the perivascular space
as they are processed by the clearance systems in the brain. This may in turn
lead the denaturation of PVMs and astrocyte activation. The risk of
neurodegeneration may be enhanced by exposure to particulate air pollutants
during brain development following the perivascular accumulation of beta-sheet
rich waste proteins.
PMID- 28408869
TI - Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical
Orientation Maps.
AB - Competitive interactions are believed to underlie many types of cortical
processing, ranging from memory formation, attention and development of cortical
functional organization (e.g., development of orientation maps in primary visual
cortex). In the latter case, the competitive interactions happen along the
cortical surface, with local populations of neurons reinforcing each other, while
competing with those displaced more distally. This specific configuration of
lateral interactions is however in stark contrast with the known properties of
the anatomical substrate, i.e., excitatory connections (mediating reinforcement)
having longer reach than inhibitory ones (mediating competition). No satisfactory
biologically plausible resolution of this conflict between anatomical measures,
and assumed cortical function has been proposed. Recently a specific pattern of
delays between different types of neurons in cat cortex has been discovered,
where direct mono-synaptic excitation has approximately the same delay, as the
combined delays of the disynaptic inhibitory interactions between excitatory
neurons (i.e., the sum of delays from excitatory to inhibitory and from
inhibitory to excitatory neurons). Here we show that this specific pattern of
delays represents a biologically plausible explanation for how short-range
inhibition can support competitive interactions that underlie the development of
orientation maps in primary visual cortex. We demonstrate this statement
analytically under simplifying conditions, and subsequently show using network
simulations that development of orientation maps is preserved when long-range
excitation, direct inhibitory to inhibitory interactions, and moderate inequality
in the delays between excitatory and inhibitory pathways is added.
PMID- 28408871
TI - Focused and Sustained Attention Is Modified by a Goal-Based Rehabilitation in
Parkinsonian Patients.
AB - Rehabilitation for patients with Parkinson's disease (PD) is based on cognitive
strategies that exploit attention. Parkinsonians exhibit impairments in divided
attention and interference control. Nevertheless, the effectiveness of specific
rehabilitation treatments based on attention suggests that other attentional
functions are preserved. Data about attention are conflicting in PD, and it is
not clear whether rehabilitative treatments that entail attentional strategies
affect attention itself. Reaction times (RTs) represent an instrument to explore
attention and investigate whether changes in attentional performances parallel
rehabilitation induced-gains. RTs of 103 parkinsonian patients in "on" state,
without cognitive deficits, were compared with those of a population of 34
healthy controls. We studied those attentional networks that subtend the use of
cognitive strategies in motor rehabilitation: alertness and focused and sustained
attention, which is a component of the executive system. We used visual and
auditory RTs to evaluate alertness and multiple choices RTs (MC RTs) to explore
focused and sustained attention. Parkinsonian patients underwent these tasks
before and after a 4-week multidisciplinary, intensive and goal-based
rehabilitation treatment (MIRT). Unified Parkinson's Disease Rating Scale (UPDRS)
III and Timed Up and Go test (TUG) were assessed at the enrollment and at the end
of MIRT to evaluate the motor-functional effectiveness of treatment. We did not
find differences in RTs between parkinsonian patients and controls. Further, we
found that improvements in motor-functional outcome measures after MIRT (p <
0.0001) paralleled a reduction in MC RTs (p = 0.014). No changes were found for
visual and auditory RTs. Correlation analysis revealed no association between
changes in MC RTs and improvements in UPDRS-III and TUG. These findings indicate
that alertness, as well as focused and sustained attention, are preserved in "on"
state. This explains why Parkinsonians benefit from a goal-based rehabilitation
that entails the use of attention. The reduction in MC RTs suggests a positive
effect of MIRT on the executive component of attention and indicates that this
type of rehabilitation provides benefits by exploiting executive functions. This
ensues from different training approaches aimed at bypassing the dysfunctional
basal ganglia circuit, allowing the voluntary execution of the defective
movements. These data suggest that the effectiveness of a motor rehabilitation
tailored for PD lies on cognitive engagement.
PMID- 28408870
TI - Homeostatic Changes in GABA and Glutamate Receptors on Excitatory Cortical
Neurons during Sleep Deprivation and Recovery.
AB - Neuronal activity is regulated in a homeostatic manner through changes in
inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using
immunofluorescent staining, we examined whether calcium/calmodulin-dependent
protein kinase IIalpha (CaMKIIalpha)-labeled (+) excitatory neurons in the barrel
cortex undergo such homeostatic regulation following enforced waking with
associated cortical activation during the day when mice normally sleep the
majority of the time. Sleep deprived mice were prevented from falling asleep by
unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep
freely following deprivation. In parallel with changes in c-Fos reflecting
changes in activity, (beta2-3 subunits of) GABAA Rs were increased on the
membrane of CaMKIIalpha+ neurons with enforced waking and returned to baseline
levels with SR in barrel cortex on sides both contra- and ipsilateral to the
whisker stimulation. The GABAAR increase was correlated with increased gamma
electroencephalographic (EEG) activity across conditions. On the other hand,
(GluA1 subunits of) AMPA Rs were progressively removed from the membrane of
CaMKIIalpha+ neurons by (Rab5+) early endosomes during enforced waking and
returned to the membrane by (Rab11+) recycling endosomes during SR. The
internalization of the GluA1Rs paralleled the expression of Arc, which mediates
homeostatic regulation of AMPA receptors through an endocytic pathway. The
reciprocal changes in GluA1Rs relative to GABAARs suggest homeostatic down
scaling during enforced waking and sensory stimulation and restorative up-scaling
during recovery sleep. Such homeostatic changes with sleep-wake states and their
associated cortical activities could stabilize excitability and activity in
excitatory cortical neurons.
PMID- 28408872
TI - Social Interaction Affects Neural Outcomes of Sign Language Learning As a Foreign
Language in Adults.
AB - Children naturally acquire a language in social contexts where they interact with
their caregivers. Indeed, research shows that social interaction facilitates
lexical and phonological development at the early stages of child language
acquisition. It is not clear, however, whether the relationship between social
interaction and learning applies to adult second language acquisition of
syntactic rules. Does learning second language syntactic rules through social
interactions with a native speaker or without such interactions impact behavior
and the brain? The current study aims to answer this question. Adult Japanese
participants learned a new foreign language, Japanese sign language (JSL), either
through a native deaf signer or via DVDs. Neural correlates of acquiring new
linguistic knowledge were investigated using functional magnetic resonance
imaging (fMRI). The participants in each group were indistinguishable in terms of
their behavioral data after the instruction. The fMRI data, however, revealed
significant differences in the neural activities between two groups. Significant
activations in the left inferior frontal gyrus (IFG) were found for the
participants who learned JSL through interactions with the native signer. In
contrast, no cortical activation change in the left IFG was found for the group
who experienced the same visual input for the same duration via the DVD
presentation. Given that the left IFG is involved in the syntactic processing of
language, spoken or signed, learning through social interactions resulted in an
fMRI signature typical of native speakers: activation of the left IFG. Thus,
broadly speaking, availability of communicative interaction is necessary for
second language acquisition and this results in observed changes in the brain.
PMID- 28408873
TI - Neurofeedback of Slow Cortical Potentials in Children with Attention
Deficit/Hyperactivity Disorder: A Multicenter Randomized Trial Controlling for
Unspecific Effects.
AB - Background: Neurofeedback (NF) in children with attention-deficit/hyperactivity
disorder (ADHD) has been investigated in a series of studies over the last years.
Previous studies did not unanimously support NF as a treatment in ADHD. Most
studies did not control for unspecific treatment effects and did not demonstrate
that self-regulation took place. The present study examined the efficacy of NF in
comparison to electromyographic (EMG) feedback to control for unspecific effects
of the treatment, and assessed self-regulation of slow cortical potentials
(SCPs). Methods: A total of 150 children aged 7-9 years diagnosed with ADHD (82%
male; 43% medicated) were randomized to 25 sessions of feedback of SCPs (NF) or
feedback of coordination of the supraspinatus muscles (EMG). The primary endpoint
was the change in parents' ratings of ADHD core symptoms 4 weeks after the end of
treatment compared to pre-tests. Results: Children in both groups showed reduced
ADHD-core symptoms (NF 0.3, 95% CI -0.42 to -0.18; EMG 0.13, 95% CI -0.26 to
0.01). NF showed a significant superiority over EMG (treatment difference 0.17,
95% CI 0.02-0.3, p = 0.02). This yielded an effect size (ES) of d = 0.57 without
and 0.40 with baseline observation carried forward (BOCF). The sensitivity
analysis confirmed the primary result. Successful self-regulation of brain
activity was observed only in NF. As a secondary result teachers reported no
superior improvement from NF compared to EMG, but within-group analysis revealed
effects of NF on the global ADHD score, inattention, and impulsivity. In
contrast, EMG feedback did not result in changes despite more pronounced self
regulation learning. Conclusions: Based on the primary parent-rated outcome NF
proved to be superior to a semi-active EMG feedback treatment. The study supports
the feasibility and efficacy of NF in a large sample of children with ADHD, based
on both specific and unspecific effects. Trial Register: Current controlled
trials ISRCTN76187185, registered 5 February 2009.
PMID- 28408874
TI - Editorial: Mapping Psychopathology with fMRI and Effective Connectivity Analysis.
PMID- 28408875
TI - APAs Constraints to Voluntary Movements: The Case for Limb Movements Coupling.
AB - When rhythmically moving two limbs in either the same or in opposite directions,
one coupling mode meets constraints that are absent in the other mode.
Isodirectional (ISO) flexion-extensions of the ipsilateral hand and foot can be
easily performed with either the hand prone or supine. Instead, antidirectional
(ANTI) movements require attentive effort and irresistibly tend to reverse into
ISO when frequency increases. Experimental evidence indicates that the direction
dependent easy-difficult dichotomy is caused by interference of the anticipatory
postural commands associated to movements of one limb with voluntary commands to
the other limb. Excitability of the resting wrist muscles is subliminally
modulated at the period of ipsilateral foot oscillations, being phase-opposite in
the antagonists and distributed so as to facilitate ISO and obstacle ANTI
coupling of the hand (either prone or supine) with the foot. Modulation is driven
by cortical signals dispatched to the forearm simultaneously with the voluntary
commands moving the foot. If right foot oscillations are performed when standing
on the left foot with the right hand touching a fixed support, the subliminal
excitability modulation is replaced by overt contractions of forearm muscles
conforming the APAs features. This suggests that during hand-foot ANTI coupling
the voluntary commands to forearm muscles are contrasted by APAs commands of
opposite sign linked to foot oscillations. Correlation between the easy-difficult
dichotomy and the APAs distribution is also found in coupled adduction-abduction
of the arms or hands in the transverse plane and in coupled flexion-extension of
the arms in the parasagittal plane. In all these movements, APAs commands linked
to the movement of each limb reach the motor pathways to the contralateral
muscles homologous to the prime movers and can interfere during coupling with
their voluntary activation. APAs are also generated in postural muscles of trunk
and lower limbs and size-increase when the movement frequency is incremented. The
related increase in postural effort apparently contributes in destabilizing the
difficult coupling mode. Motor learning may rely upon more effective APAs. APAs
and focal contraction are entangled within the same voluntary action. Yet, neural
diseases may selectively impair APAs, which represent a potential target for
rehabilitation.
PMID- 28408876
TI - Effects of Age-Related Macular Degeneration on Postural Sway.
AB - Purpose: To compare the impact of unilateral vs. bilateral age-related macular
degeneration (AMD) on postural sway, and the influence of different visual
conditions. The hypothesis of our study was that the impact of AMD will be
different between unilateral and bilateral AMD subjects compared to age-matched
healthy elderly. Methods: Postural stability was measured with a platform
(TechnoConcept(r)) in 10 elderly unilateral AMD subjects (mean age: 71.1 +/- 4.6
years), 10 elderly bilateral AMD subjects (mean age: 70.8 +/- 6.1 years), and 10
healthy age-matched control subjects (mean age: 69.8 +/- 6.3 years). Four visual
conditions were tested: both eyes viewing condition (BEV), dominant eye viewing
(DEV), non-dominant eye viewing (NDEV), and eyes closed (EC). We analyzed the
surface area, the length, the mean speed, the anteroposterior (AP), and
mediolateral (ML) displacement of the center of pressure (CoP). Results:
Bilateral AMD subjects had a surface area (p < 0.05) and AP displacement of the
CoP (p < 0.01) higher than healthy elderly. Unilateral AMD subjects had more AP
displacement of the CoP (p < 0.05) than healthy elderly. Conclusions: We suggest
that ADM subjects could have poor postural adaptive mechanisms leading to
increase their postural instability. Further studies will aim to improve
knowledge on such issue and to develop reeducation techniques in these patients.
PMID- 28408877
TI - Dull to Social Acceptance Rather than Sensitivity to Social Ostracism in
Interpersonal Interaction for Depression: Behavioral and Electrophysiological
Evidence from Cyberball Tasks.
AB - Objectives: Impairments in interpersonal relationships in depression present as
irritability, pessimism, and withdrawal, and play an important role in the onset
and maintenance of the disorder. However, we know little about the neurological
causes of this impaired interpersonal function. This study used the event-related
brain potential (ERP) version of the Cyberball paradigm to investigate the
emotions and neural activities in depressive patients during social inclusion and
exclusion simultaneously to explore neuropsychological mechanisms. Methods:
Electrophysiological data were recorded when 27 depressed patients and 23 healthy
controls (HCs) performed a virtual ball tossing game (Cyberball) during which the
participants believed they were playing with two other co-players over the
internet. The Cyberball paradigm included two other conditions; inclusion during
which participants received the ball with the same probability as the other
players to experience a feeling of acceptance, and exclusion during which the
participants experienced a feeling of ostracism when the other two players threw
the ball with each other. The Positive and Negative Affect Schedule (PANAS) was
used as a baseline and after each block during the Cyberball to assess positive
and negative effects. In addition, a brief Need-Threat Scale (NTS) was used to
assess the fulfillment of basic needs of subjects after each block and 10 min
after ostracism. Moreover, the relationship between the ERP data of depression
and clinical symptoms was analyzed. Results: Exclusion compared to inclusion
Cyberball caused a decrease in positive affect and an increase in negative
affect. The group differences were only found in the positive affect. Moreover,
patients reported a lower level of basic needs than did HCs after social
inclusion, but a similar level of basic needs after social exclusion. At the
electrophysiological level, patients showed decreased P3 amplitudes compared to
HCs in social inclusion, and P3 amplitudes were borderline negatively correlated
with their scores of anhedonia symptoms. Limitations: A limitation of our study
was that the subjects' criteria were different. Conclusions: The behavioral and
electrophysiological results indicated that the interpersonal problems in
depressive patients were mainly due to deficits in processing the pleasurable
social stimuli rather than aversive social cues.
PMID- 28408878
TI - Reward Based Motor Adaptation Mediated by Basal Ganglia.
AB - It is widely accepted that the basal ganglia (BG) play a key role in action
selection and reinforcement learning. However, despite considerable number of
studies, the BG architecture and function are not completely understood. Action
selection and reinforcement learning are facilitated by the activity of
dopaminergic neurons, which encode reward prediction errors when reward outcomes
are higher or lower than expected. The BG are thought to select proper motor
responses by gating appropriate actions, and suppressing inappropriate ones. The
direct striato-nigral (GO) and the indirect striato-pallidal (NOGO) pathways have
been suggested to provide the functions of BG in the two-pathway concept.
Previous models confirmed the idea that these two pathways can mediate the
behavioral choice, but only for a relatively small number of potential behaviors.
Recent studies have provided new evidence of BG involvement in motor adaptation
tasks, in which adaptation occurs in a non-error-based manner. In such tasks,
there is a continuum of possible actions, each represented by a complex neuronal
activity pattern. We extended the classical concept of the two-pathway BG by
creating a model of BG interacting with a movement execution system, which allows
for an arbitrary number of possible actions. The model includes sensory and
premotor cortices, BG, a spinal cord network, and a virtual mechanical arm
performing 2D reaching movements. The arm is composed of 2 joints (shoulder and
elbow) controlled by 6 muscles (4 mono-articular and 2 bi-articular). The spinal
cord network contains motoneurons, controlling the muscles, and sensory
interneurons that receive afferent feedback and mediate basic reflexes. Given a
specific goal-oriented motor task, the BG network through reinforcement learning
constructs a behavior from an arbitrary number of basic actions represented by
cortical activity patterns. Our study confirms that, with slight modifications,
the classical two-pathway BG concept is consistent with results of previous
studies, including non-error based motor adaptation experiments, pharmacological
manipulations with BG nuclei, and functional deficits observed in BG-related
motor disorders.
PMID- 28408879
TI - Comparison of In Vivo and Ex Vivo MRI for the Detection of Structural
Abnormalities in a Mouse Model of Tauopathy.
AB - With increasingly large numbers of mouse models of human disease dedicated to MRI
studies, compromises between in vivo and ex vivo MRI must be fully understood in
order to inform the choice of imaging methodology. We investigate the application
of high resolution in vivo and ex vivo MRI, in combination with tensor-based
morphometry (TBM), to uncover morphological differences in the rTg4510 mouse
model of tauopathy. The rTg4510 mouse also offers a novel paradigm by which the
overexpression of mutant tau can be regulated by the administration of
doxycycline, providing us with a platform on which to investigate more subtle
alterations in morphology with morphometry. Both in vivo and ex vivo MRI allowed
the detection of widespread bilateral patterns of atrophy in the rTg4510 mouse
brain relative to wild-type controls. Regions of volume loss aligned with
neuronal loss and pathological tau accumulation demonstrated by
immunohistochemistry. When we sought to investigate more subtle structural
alterations in the rTg4510 mice relative to a subset of doxycycline-treated
rTg4510 mice, ex vivo imaging enabled the detection of more regions of
morphological brain changes. The disadvantages of ex vivo MRI may however
mitigate this increase in sensitivity: we observed a 10% global shrinkage in
brain volume of the post-mortem tissues due to formalin fixation, which was most
notable in the cerebellum and olfactory bulbs. However, many central brain
regions were not adversely affected by the fixation protocol, perhaps due to our
"in-skull" preparation. The disparity between our TBM findings from in vivo and
ex vivo MRI underlines the importance of appropriate study design, given the
trade-off between these two imaging approaches. We support the utility of in vivo
MRI for morphological phenotyping of mouse models of disease; however, for
subtler phenotypes, ex vivo offers enhanced sensitivity to discrete morphological
changes.
PMID- 28408880
TI - A Bayesian Model for the Prediction and Early Diagnosis of Alzheimer's Disease.
AB - Alzheimer's disease treatment is still an open problem. The diversity of
symptoms, the alterations in common pathophysiology, the existence of
asymptomatic cases, the different types of sporadic and familial Alzheimer's and
their relevance with other types of dementia and comorbidities, have already
created a myth-fear against the leading disease of the twenty first century. Many
failed latest clinical trials and novel medications have revealed the early
diagnosis as the most critical treatment solution, even though scientists tested
the amyloid hypothesis and few related drugs. Unfortunately, latest studies have
indicated that the disease begins at the very young ages thus making it difficult
to determine the right time of proper treatment. By taking into consideration all
these multivariate aspects and unreliable factors against an appropriate
treatment, we focused our research on a non-classic statistical evaluation of the
most known and accepted Alzheimer's biomarkers. Therefore, in this paper, the
code and few experimental results of a computational Bayesian tool have being
reported, dedicated to the correlation and assessment of several Alzheimer's
biomarkers to export a probabilistic medical prognostic process. This new
statistical software is executable in the Bayesian software Winbugs, based on the
latest Alzheimer's classification and the formulation of the known relative
probabilities of the various biomarkers, correlated with Alzheimer's progression,
through a set of discrete distributions. A user-friendly web page has been
implemented for the supporting of medical doctors and researchers, to upload
Alzheimer's tests and receive statistics on the occurrence of Alzheimer's disease
development or presence, due to abnormal testing in one or more biomarkers.
PMID- 28408881
TI - Commentary: Preconditioning tDCS facilitates subsequent tDCS effect on skill
acquisition in older adults.
PMID- 28408882
TI - Targeted Nanotechnology in Glioblastoma Multiforme.
AB - Gliomas, and in particular glioblastoma multiforme, are aggressive brain tumors
characterized by a poor prognosis and high rates of recurrence. Current treatment
strategies are based on open surgery, chemotherapy (temozolomide) and
radiotherapy. However, none of these treatments, alone or in combination, are
considered effective in managing this devastating disease, resulting in a median
survival time of less than 15 months. The efficiency of chemotherapy is mainly
compromised by the blood-brain barrier (BBB) that selectively inhibits drugs from
infiltrating into the tumor mass. Cancer stem cells (CSCs), with their unique
biology and their resistance to both radio- and chemotherapy, compound tumor
aggressiveness and increase the chances of treatment failure. Therefore, more
effective targeted therapeutic regimens are urgently required. In this article,
some well-recognized biological features and biomarkers of this specific subgroup
of tumor cells are profiled and new strategies and technologies in nanomedicine
that explicitly target CSCs, after circumventing the BBB, are detailed. Major
achievements in the development of nanotherapies, such as organic poly(propylene
glycol) and poly(ethylene glycol) or inorganic (iron and gold) nanoparticles that
can be conjugated to metal ions, liposomes, dendrimers and polymeric micelles,
form the main scope of this summary. Moreover, novel biological strategies
focused on manipulating gene expression (small interfering RNA and clustered
regularly interspaced short palindromic repeats [CRISPR]/CRISPR associated
protein 9 [Cas 9] technologies) for cancer therapy are also analyzed. The aim of
this review is to analyze the gap between CSC biology and the development of
targeted therapies. A better understanding of CSC properties could result in the
development of precise nanotherapies to fulfill unmet clinical needs.
PMID- 28408883
TI - Alisol A 24-Acetate and Alisol B 23-Acetate Induced Autophagy Mediates Apoptosis
and Nephrotoxicity in Human Renal Proximal Tubular Cells.
AB - Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are
abundant in Rhizoma alismatis. In the present study, we evaluated the induction
of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal
tubular (HK-2) cells by activating autophagy and also explored its regulation on
PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were
considered to be new bioindicators of nephrotoxicity. Interestingly, the protein
expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly
increased by 23B and 24A in vivo and in vitro. Furthermore, cell apoptosis could
be triggered by 23B and 24A via significantly decreasing the protein expression
and mRNA levels of Bcl-2 and Bcl-xl. Autophagy of HK-2 cells could be induced by
both 23B and 24A via significantly enhancing the ratio of LC3II/LC3I, the protein
expression of Beclin-1 as well as the mRNA levels of LC3 and Beclin-1. Meanwhile,
PI3K/Akt/mTOR signaling pathway could be inhibited by these two compounds. An
autophagy inhibitor, 3-methyladenine, could partially reverse cell viability and
conversely change the ratio of LC3II/LC3I and the protein expression of Bcl-2 and
Kim-1. Thus this study helped to understand that 23B and 24A induced autophagy
resulted in apoptosis and nephrotoxicity through inhibiting PI3K/Akt/mTOR
signaling pathway, facilitating further studies for nephrotoxicity induced by
these two compounds and could be beneficial for safe use of Rhizoma alismatis in
clinic.
PMID- 28408884
TI - Effect of CYP3A4*1G and CYP3A5*3 Polymorphisms on Pharmacokinetics and
Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects.
AB - Ticagrelor is the first reversible, direct-acting, potent P2Y12 receptor
antagonist in management of acute coronary syndromes. It is rapidly absorbed and
extensively metabolized. AR-C124910XX, the major active metabolite, antagonizes
the P2Y12 receptor at approximately equal potency. The metabolism of ticagrelor
to AR-C124910XX involves CYP3A4 and CYP3A5. CYP3A polymorphisms have been well
documented, and CYP3A4*1G (g.20230G>A, rs2242480) and CYP3A5*3 (g.6986A>G,
rs776746) are the most important single nucleotide polymorphisms in Chinese.
Genetic differences in CYP3A4 and CYP3A5 expression in human volunteers and
patients might affect the clearance of ticagrelor or AR-C124910XX in vivo
resulting in subsequent variable patient response. Thus, this study is designed
to explore the effects of CYP3A4*1G and CYP3A5*3 polymorphisms on the
pharmacokinetics and pharmcodynamics of ticagrelor in healthy Chinese subjects.
The results indicated that the CYP3A4*1G polymorphism significantly influenced
the pharmacokinetics of AR-C124910XX, and it may be more important than CYP3A5*3
with respect to influencing ticagrelor pharmacokinetics by increasing CYP3A4
activity. However, the significant effect of CYP3A4*1G polymorphism on AR
C124910XX plasma levels did not translate into detectable effect on inhibition of
platelet aggregation. Therefore, it seems not necessary to adjust the dosage of
ticagrelor according to the CYP3A4 or 3A5 genotype.
PMID- 28408857
TI - Measurement of the phase difference between short- and long-distance amplitudes
in the [Formula: see text] decay.
AB - A measurement of the phase difference between the short- and long-distance
contributions to the [Formula: see text] decay is performed by analysing the
dimuon mass distribution. The analysis is based on pp collision data
corresponding to an integrated luminosity of 3[Formula: see text] collected by
the LHCb experiment in 2011 and 2012. The long-distance contribution to the
[Formula: see text] decay is modelled as a sum of relativistic Breit-Wigner
amplitudes representing different vector meson resonances decaying to muon pairs,
each with their own magnitude and phase. The measured phases of the [Formula: see
text] and [Formula: see text] resonances are such that the interference with the
short-distance component in dimuon mass regions far from their pole masses is
small. In addition, constraints are placed on the Wilson coefficients, [Formula:
see text] and [Formula: see text], and the branching fraction of the short
distance component is measured.
PMID- 28408885
TI - Fludarabine Inhibits KV1.3 Currents in Human B Lymphocytes.
AB - Fludarabine (F-ara-A) is a purine analog commonly used in the treatment of
indolent B cell malignancies that interferes with different aspects of DNA and
RNA synthesis. KV1.3 K+ channels are membrane proteins involved in the
maintenance of K+ homeostasis and the resting potential of the cell, thus
controlling signaling events, proliferation and apoptosis in lymphocytes. Here we
show that F-ara-A inhibits KV currents in human B lymphocytes. Our data indicate
that KV1.3 is expressed in both BL2 and Dana B cell lines, although total KV1.3
levels were higher in BL2 than in Dana cells. However, KV currents in the plasma
membrane were similar in both cell lines and were abrogated by the specific KV1.3
channel inhibitor PAP-1, indicating that KV1.3 accounts for most of the KV
currents in these cell lines. F-ara-A, at a concentration (3.5 MUM) similar to
that achieved in the plasma of fludarabine phosphate-treated patients (3 MUM),
inhibited KV1.3 currents by 61 +/- 6.3% and 52.3 +/- 6.3% in BL2 and Dana B
cells, respectively. The inhibitory effect of F-ara-A was concentration-dependent
and showed an IC50 value of 0.36 +/- 0.04 MUM and a nH value of 1.07 +/- 0.15 in
BL2 cells and 0.34 +/- 0.13 MUM (IC50 ) and 0.77 +/- 0.11 (nH ) in Dana cells. F
ara-A inhibition of plasma membrane KV1.3 was observed irrespective of its
cytotoxic effect on the cells, BL2 cells being sensitive and Dana cells resistant
to F-ara-A cytotoxicity. Interestingly, PAP-1, at concentrations as high as 10
MUM, did not affect the viability of BL2 and Dana cells, indicating that blockage
of KV1.3 in these cells is not toxic. Finally, F-ara-A had no effect on
ectopically expressed KV1.3 channels, suggesting an indirect mechanism of current
inhibition. In summary, our results describe the inhibitory effect of F-ara-A on
the activity of KV1.3 channel. Although KV1.3 inhibition is not sufficient to
induce cell death, further research is needed to determine whether it might still
contribute to F-ara-A cytotoxicity in sensitive cells or be accountable for some
of the clinical side effects of the drug.
PMID- 28408886
TI - A Pointwise Method for Identifying Biomechanical Heterogeneity of the Human
Gallbladder.
AB - Identifying the heterogeneous biomechanical property of human gallbladder (GB)
walls from non-invasive measurements can have clinical significance in patient
specific modeling and acalculous biliary pain diagnosis. In this article, a
pointwise method was proposed to measure the heterogeneity of ten samples of
human GB during refilling. Three different points, two on the equator of GB body
90 degrees apart and one on the apex of GB fundus, were chosen to represent the
typical regions of interest. The stretches at these points were estimated from
ultrasound images of the GB during the bile emptying phase based on an analytical
model. The model was validated against the experimental data of a lamb GB. The
material parameters at the different points were determined inversely by making
use of a structure-based anisotropic constitutive model. This anisotropic model
yielded much better accuracy when compared to a number of phenomenologically
based constitutive laws, as demonstrated by its significantly reduced least
square errors in stress curve fitting. The results confirmed that the human GB
wall material was heterogeneous, particularly toward the apex region. Our study
also suggested that non-uniform wall thickness of the GB was important in
determining the material parameters, in particular, on the parameters associated
with the properties of the matrix and the longitudinal fibers-the difference
could be as large as 20-30% compared to that of the uniform thickness model.
PMID- 28408887
TI - Evaluation of Salivary and Serum Antioxidant and Oxidative Stress Statuses in
Patients with Chronic Periodontitis: A Case-Control Study.
AB - Aim: Local bacteria stimulate polymorphonuclear neutrophils to release reactive
oxygen species in periodontitis. Increased levels of oxidative stress play a
significant role in the pathogenesis of periodontitis. Therefore, this study
aimed to evaluate total salivary and serum antioxidant capacity and
malondialdehyde in patients with chronic periodontitis. Materials and methods:
Fifty-five healthy subjects and 55 patients with chronic periodontitis, with an
age range of 30-50 years, were evaluated. After clinical examination and case
selection, unstimulated whole saliva was collected in the morning. Blood samples
were taken from the antecubital vein. Total antioxidant capacity and
malondialdehyde levels were evaluated by spectrophotometric assay. Data were
analyzed with t-test, using Stata.11 software program. Results: The periodontitis
group exhibited lower salivary (0.16) and serum (0.36) total antioxidant capacity
(P = 0.11) compared to the control group. Mean salivary malondialdehyde levels in
the case and control groups were 0.80 +/- 0.09 and 0.42 +/- 0.08, respectively.
The results showed significantly higher levels of salivary and serum
malondialdehyde in the periodontitis group. Gender did not have any effect on
antioxidant and oxidative stress levels. Conclusion: This study indicated
increased levels of salivary and serum oxidative stresses in patients with
chronic periodontitis. Total antioxidant capacity was mildly lower in the saliva
and serum of these patients. Higher malondialdehyde levels with no changes in
antioxidant status can result in systemic and local complications in these
patients.
PMID- 28408888
TI - Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by
Paeonol.
AB - Pulmonary fibrosis is a severe and progressive disease that is characterized by
an abnormal deposition of extracellular matrix, such as collagens. The
pathogenesis of this disease may be initiated by oxidative damage of lung
epithelial cells by fibrogenic stimuli, leading to lung inflammation, which in
turn promotes various lung fibrotic responses. The profibrogenic effect of
transforming growth factor-beta1 (TGF-beta1) on lung fibroblasts is crucial for
the pathogenesis of this disease. Paeonol, the main phenolic compound present in
the Chinese herb Paeonia suffruticosa, has antioxidant and anti-inflammatory
properties. However, whether paeonol has therapeutic effects against pulmonary
fibrosis remains unclear. Using a murine model, we showed that 21 days after the
insult, intratracheal bleomycin caused pulmonary inflammation and fibrosis, as
evidenced by lung histopathological manifestations and increase in various
indices. The inflammatory indices included an increase in total cell count,
differential cell count, and total protein concentration in bronchoalveolar
lavage fluid. The fibrotic indices included an increase in lung levels of TGF
beta1, total collagen, type 1alpha1 collagen (COL1A1), and alpha-smooth muscle
actin (alpha-SMA; a marker of myofibroblasts). Bleomycin also was found to cause
an increase in oxidative stress as reflected by increased levels of
malondialdehyde and 4-hydroxynonenal in the lungs. Importantly, all these
pathophysiological events were suppressed by daily treatment with paeonol. Using
human lung fibroblasts, we further demonstrated that exposure of human lung
fibroblasts to TGF-beta1 increased productions of alpha-SMA and COL1A1, both of
which were inhibited by inhibitors of Jun N-terminal kinase (JNK), p38, and
Smad3. JNK and p38 are two subfamily members of mitogen-activated protein kinases
(MAPKs), whereas Smad3 is a transcription factor. TGF-beta1 exposure also
increased the phosphorylation of JNK, p38, and Smad3 prior to the induction of
alpha-SMA and COL1A1. Notably, all these TGF-beta1-induced cellular events were
suppressed by paeonol treatment. Our findings suggest that paeonol has
antioxidant, anti-inflammatory, and anti-fibrotic functions against bleomycin
induced pulmonary fibrosis in mice. The beneficial effect of paeonol may be, at
least in part, mediated through the inhibition of the MAPKs/Smad3 signaling.
PMID- 28408889
TI - Effects of Sesame (Sesamum indicum L.) Supplementation on Creatine Kinase,
Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi
Professional Soccer Players.
AB - Nutritional intervention with antioxidants rich foods has been considered a
strategy to minimize the effects of overtraining in athletes. This experimental,
randomized, and placebo-controlled study evaluated the effects of consumption of
sesame (Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic
inflammation, and aerobic performance in male semi-professional soccer players.
Twenty athletes were randomly assigned to groups that received 40 g (two
tablespoons) per day of sesame or a placebo during 28 days of regular training
(exposed to routine training that includes loads of heavy training in the final
half of the season). Before and after intervention, creatine kinase (CK), lactate
dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C
reactive protein (hs-CRP), and aerobic capacity were evaluated. Before
intervention, a physiologic imbalance was noted in both groups related to CK and
LDH levels. Sesame intake caused a reduction of CK (19%, p < 0.05), LDH (37%, p <
0.05), MDA (55%, p < 0.05) and hs-CRP (53%, p < 0.05) and increased SOD (14%, p <
0.05), vitamin A (25%, p < 0.05), and vitamin E (65%, p < 0.05) in the
experimental group. These phenomena were accompanied by increased aerobic
capacity (17%, p < 0.05). The placebo group showed an increase in CK (5%, p <
0.05) and no significant change in LDH, SOD or vitamin A. MDA levels decreased
(21%, p < 0.05) and vitamin E increased (14%, p < 0.05) in the placebo group, but
to a much lesser extent than in the experimental group. These results show that
sesame consumption may reduce muscle damage and oxidative stress while improving
the aerobic capacity in soccer players.
PMID- 28408891
TI - Video Games Exposure and Sexism in a Representative Sample of Adolescents.
AB - Research has indicated that many video games are saturated with stereotypes of
women and that these contents may cultivate sexism. The purpose of this study was
to assess the relationship between video game exposure and sexism for the first
time in a large and representative sample. Our aim was also to measure the
strength of this association when two other significant and well-studied sources
of sexism, television exposure and religiosity, were also included in a
multivariate model. A representative sample of 13520 French youth aged 11-19
years completed a survey measuring weekly video game and television exposure,
religiosity, and sexist attitudes toward women. Controlling for gender and
socioeconomic level, results showed that video game exposure and religiosity were
both related to sexism. Implications of these results for future research on
sexism in video games are discussed.
PMID- 28408892
TI - Conceptualizing the Dynamics between Bicultural Identification and Personal
Social Networks.
AB - : An adequate understanding of the acculturation processes affecting immigrants
and their descendants involves ascertaining the dynamic interplay between the way
these individuals manage their multiple (and sometimes conflictual) cultural
value systems and identifications and possible changes in their social networks.
To fill this gap, the present research examines how key acculturation variables
(e.g., strength of ethnic/host cultural identifications, bicultural identity
integration or BII) relate to the composition and structure of bicultural
individuals' personal social networks. In Study 1, we relied on a generationally
and culturally diverse community sample of 123 Latinos residing in the US.
Participants nominated eight individuals (i.e., alters) from their habitual
social networks and across two relational domains: friendships and colleagues.
Results indicated that the interconnection of same ethnicity alters across
different relationship domains is linked to cultural identifications, while the
amount of coethnic and host individuals in the network is not. In particular,
higher interconnection between Latino friends and colleagues was linked to lower
levels of U.S. IDENTIFICATION: Conversely, the interconnection of non-Latino
friends and colleagues was associated with lower levels of Latino identification.
This pattern of results suggests that the relational context for each type of
cultural identification works in a subtractive and inverse manner. Further, time
spent in the US was linked to both Latino and U.S. cultural identifications, but
this relationship was moderated by the level of BII. Specifically, the
association between time in the US and strength of both cultural identities was
stronger for individuals reporting low levels of BII. Taking the findings from
Study 1 as departure point, Study 2 used an agent-based model data simulation
approach to explore the dynamic ways in which the content and the structure of an
immigrant's social network might matter over time in predicting three possible
identity patterns: coexisting cultural identifications, conflicting cultural
identifications, and a mixture of the two. These simulations allowed us to detect
network constellations, which lead to identification or disidentification with
both cultures. We showed that distinct patterns of social relations do not lead
to identity outcomes in a deterministic fashion, but that often many different
outcomes are probable.
PMID- 28408890
TI - Assessing the Role of the 'Unity Assumption' on Multisensory Integration: A
Review.
AB - There has been longstanding interest from both experimental psychologists and
cognitive neuroscientists in the potential modulatory role of various top-down
factors on multisensory integration/perception in humans. One such top-down
influence, often referred to in the literature as the 'unity assumption,' is
thought to occur in those situations in which an observer considers that various
of the unisensory stimuli that they have been presented with belong to one and
the same object or event (Welch and Warren, 1980). Here, we review the possible
factors that may lead to the emergence of the unity assumption. We then
critically evaluate the evidence concerning the consequences of the unity
assumption from studies of the spatial and temporal ventriloquism effects, from
the McGurk effect, and from the Colavita visual dominance paradigm. The research
that has been published to date using these tasks provides support for the claim
that the unity assumption influences multisensory perception under at least a
subset of experimental conditions. We then consider whether the notion has been
superseded in recent years by the introduction of priors in Bayesian causal
inference models of human multisensory perception. We suggest that the prior of
common cause (that is, the prior concerning whether multisensory signals
originate from the same source or not) offers the most useful way to quantify the
unity assumption as a continuous cognitive variable.
PMID- 28408893
TI - Bridging the Gap across the Transition to Coparenthood: Triadic Interactions and
Coparenting Representations from Pregnancy through 12 Months Postpartum.
AB - Most family researchers agree that the coparenting relationship emerges some time
during the transition to parenthood, though it is unclear whether it originates
in pregnancy. Previous studies demonstrated that couples' positive
representations of their future coparenting relationship and harmonious
coparenting behaviors observed during prenatal triadic interactions predicted
better postpartum functioning. However, previous studies did not simultaneously
assess prenatal coparenting behaviors and representations as predictors of
postpartum coparenting. If the coparenting relationship originates during
pregnancy, these behavioral and cognitive aspects of prenatal coparenting should
show associations with their postpartum counterparts. Based on family systems-,
attachment-, and social-learning theory, the first aim in this study was to
explore whether prenatal coparenting representations and behaviors are associated
with postpartum coparenting, which would suggest that both cognitive and
behavioral aspects of the coparenting relationship emerge during pregnancy. A
second aim was to determine whether parental coparenting representations are
consistent with concurrently observed coparenting behaviors. A sample of 55
couples expecting their first child was observed during triadic interactions
during pregnancy and at 3- and 12-months postpartum. Observations were coded
using the Coparenting and Family Rating System. Composite scores were formed to
reflect harmonious and antagonistic coparenting behaviors. Parents'
representations of harmonious and antagonistic coparenting were assessed via
interviews and questionnaires during pregnancy and at 3- and 12-months
postpartum. Results indicated that prenatal representations of harmonious and
antagonistic coparenting were associated with and predicted unique variance in
respective postpartum coparenting representations. Prenatal coparenting behaviors
were also associated with coparenting behaviors observed during 3-months-play and
12-months-mealtime interactions and predicted unique variance in postpartum
coparenting. Surprisingly, prenatal coparenting representations were not
associated with prenatal behaviors, though representations and behaviors were
associated at 3 months postpartum. Findings suggest that the coparenting
relationship originates during pregnancy with prenatal coparenting
representations and behaviors bridging the gap across the transition to
coparenthood. Future studies should include assessments of both cognitive and
behavioral facets of the prenatal coparenting relationship.
PMID- 28408894
TI - The Relationships between Mental Health Symptoms and Gambling Behavior in the
Transition from Adolescence to Emerging Adulthood.
AB - There is a paucity of longitudinal investigations of gambling behavior in the
transition from adolescence to emerging adulthood. We conducted a longitudinal
investigation of the associations and patterns of change between mental health
symptoms and gambling behavior. A representative sample of Norwegians completed
questionnaires containing demographic, mental health, and gambling measures at
age 17 (N = 2055), and at ages 18 (N = 1334) and 19 (N = 1277). Using latent
class analysis, three classes of gambling behavior were identified: consistent
non-gambling (71.1%), consistent non-risk gambling (23.8%), and risky-and-problem
gambling (5.1%). Being male, showing higher physical and verbal aggression and
having more symptoms of depression were associated with greater odds of belonging
to the risky-and-problem gambling class at age 17. Overall, the risky-and-problem
gambling class had the highest physical and verbal aggression, anxiety, and
depression at 19 years. Our findings elucidate the reciprocal relationship
between mental health and gambling behavior in the transition from adolescence to
emerging adulthood, and the importance of recognizing these factors in designing
targeted interventions.
PMID- 28408895
TI - Character Decomposition and Transposition Processes of Chinese Compound Words in
Rapid Serial Visual Presentation.
AB - Character order information is encoded at the initial stage of Chinese word
processing, however, its time course remains underspecified. In this study, we
assess the exact time course of the character decomposition and transposition
processes of two-character Chinese compound words (canonical, transposed, or
reversible words) compared with pseudowords using dual-target rapid serial visual
presentation (RSVP) of stimuli appearing at 30 ms per character with no inter
stimulus interval. The results indicate that Chinese readers can identify words
with character transpositions in rapid succession; however, a transposition cost
is involved in identifying transposed words compared to canonical words. In RSVP
reading, character order of words is more likely to be reversed during the period
from 30 to 180 ms for canonical and reversible words, but the period from 30 to
240 ms for transposed words. Taken together, the findings demonstrate that the
holistic representation of the base word is activated, however, the order of the
two constituent characters is not strictly processed during the very early stage
of visual word processing.
PMID- 28408896
TI - The Role of Indian Caste Identity and Caste Inconsistent Norms on Status
Representation.
AB - The Indian caste system is a complex social structure wherein social roles like
one's profession became 'hereditary,' resulting in restricted social mobility and
fixed status hierarchies. Furthermore, we argue that the inherent property of
caste heightens group identification with one's caste. Highly identified group
members would protect the identity of the group in situations when group norms
are violated. In this paper, we were interested in examining the consequence of
caste norm violation and how an individual's status is mentally represented. High
caste norms are associated with moral values while the lower caste norms are
associated with immorality. We predicted a 'black sheep effect,' that is, when
high caste individuals' group identity (caste norm violation condition) is
threatened their salient high caste identity would increase, thereby resulting in
devaluing the status of their fellow in-group member if the latter is perceived
as perpetrator. We presented participants with a social conflict situation of a
victim and a perpetrator that is 'Caste norm consistent' (Lower caste individual
as a perpetrator and higher caste individual as a victim) and vice versa 'Caste
norm inconsistent' condition (higher caste individual as perpetrator and lower
caste individual as a victim). Then, participants had to choose from nine
pictorial depictions representing the protagonists in the story on a vertical
line, with varying degrees of status distance. Results showed evidence for the
black sheep effect and, furthermore, revealed that no other identity (religious,
national, and regional) resulted in devaluing the status of fellow in-group
member. These results help us understand the 'black sheep' effect in the context
of moral norms and status representation and are discussed in the framework of
the Indian society.
PMID- 28408897
TI - Do Executive Functions Predict Binge-Drinking Patterns? Evidence from a
Longitudinal Study in Young Adulthood.
AB - Background: Impairments in executive functions (EFs) are related to binge
drinking in young adulthood, but research on how EFs influence future binge
drinking is lacking. The aim of the current report is therefore to investigate
the association between various EFs and later severity of, and change in, binge
drinking over a prolonged period during young adulthood. Methods: At baseline,
121 students reported on their alcohol habits (Alcohol use disorder
identification test; Alcohol use questionnaire). Concurrently, EFs [working
memory, reversal, set-shifting, response inhibition, response monitoring and
decision-making (with ambiguity and implicit risk)] were assessed. Eighteen
months later, information on alcohol habits for 103 of the participants were
gathered. Data were analyzed by means of multilevel regression modeling. Results:
Future severity of binge drinking was uniquely predicted by performance on the
Information sampling task, assessing risky decision-making (beta = -1.86, 95% CI:
-3.69, -0.04). None of the study variables predicted severity or change in binge
drinking. Conclusion: Future severity of binge drinking was associated with
making risky decisions in the prospect for gain, suggesting reward
hypersensitivity. Future studies should aim at clarifying whether there is a
causal association between decision-making style and binge drinking. Performance
on all executive tasks was unrelated to change in binge drinking patterns;
however, the finding was limited by overall small changes, and needs to be
confirmed with longer follow-up periods.
PMID- 28408898
TI - From Lexical Tone to Lexical Stress: A Cross-Language Mediation Model for
Cantonese Children Learning English as a Second Language.
AB - This study investigated how Cantonese lexical tone sensitivity contributed to
English lexical stress sensitivity among Cantonese children who learned English
as a second language (ESL). Five-hundred-and-sixteen second-to-third grade
Cantonese ESL children were tested on their Cantonese lexical tone sensitivity,
English lexical stress sensitivity, general auditory sensitivity, and working
memory. Structural equation modeling revealed that Cantonese lexical tone
sensitivity contributed to English lexical stress sensitivity both directly, and
indirectly through the mediation of general auditory sensitivity, in which the
direct pathway had a larger relative contribution to English lexical stress
sensitivity than the indirect pathway. These results suggest that the tone-stress
association might be accounted for by joint phonological and acoustic processes
that underlie lexical tone and lexical stress perception.
PMID- 28408899
TI - Abusive Supervision and Job Dissatisfaction: The Moderating Effects of Feedback
Avoidance and Critical Thinking.
AB - Although research on the antecedents of job dissatisfaction has been developed
greatly, we know little about the role of abusive supervision in generating job
dissatisfaction. The contingencies under which abusive supervision relates to
employees' job dissatisfaction are still unknown. The present study aimed to fill
this research gap by empirically exploring the abusive supervision-job
dissatisfaction relationship as well as examining the moderating roles of
feedback avoidance and critical thinking on this relationship. We tested the
hypotheses with data from a sample of 248 employees from a high-tech
communications company in northern China and found that: (a) abusive supervision
was positively related to job dissatisfaction; (b) the positive relationship was
moderated by both employees' feedback avoidance and critical thinking. We
conclude by extracting the theoretical as well as practical contributions, along
with a discussion of the promising directions for future research.
PMID- 28408901
TI - Serine-Rich Repeat Adhesins Contribute to Streptococcus gordonii-Induced
Maturation of Human Dendritic Cells.
AB - Dendritic cells (DCs) play a pivotal role in the induction of immunity by
recognition, capture, process, and presentation of antigens from infectious
microbes. Streptococcus gordonii is able to cause life-threatening systemic
diseases such as infective endocarditis. Serine-rich repeat (SRR) glycoproteins
of S. gordonii are sialic acid-binding adhesins mediating the bacterial adherence
to the host and the development of infective endocarditis. Thus, the SRR adhesins
are potentially involved in the bacterial adherence to DCs and the maturation and
activation of DCs required for the induction of immunity to S. gordonii. Here, we
investigated the phenotypic and functional changes of human monocyte-derived DCs
treated with wild-type S. gordonii or the SRR adhesin-deficient mutant. The
mutant poorly bound to DCs and only weakly increased the expression of CD83,
CD86, MHC class II, and PD-L1 on DCs compared with the wild-type. In addition,
the mutant induced lower levels of TNF-alpha, IL-6, and IL-12 than the wild-type
in DCs. When DCs sensitized with the mutant were co-cultured with autologous T
cells, they induced weaker proliferation and activation of T cells than DCs
stimulated with the wild-type. Blockade of SRR adhesin with 3'-sialyllactose
markedly reduced S. gordonii binding and internalization, causing attenuation of
the bacterial immunostimulatory potency in DC maturation. Collectively, our
results suggest that SRR adhesins of S. gordonii are important for maturation and
activation of DCs.
PMID- 28408900
TI - The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by
Ligand, Mutations, Agonists, and Mutated Calreticulin.
AB - A well-functioning hematopoietic system requires a certain robustness and
flexibility to maintain appropriate quantities of functional mature blood cells,
such as red blood cells and platelets. This review focuses on the cytokine
receptor that plays a significant role in thrombopoiesis: the receptor for
thrombopoietin (TPO-R; also known as MPL). Here, we survey the work to date to
understand how this receptor functions at a molecular level throughout its
lifecycle, from traffic to the cell surface, dimerization and binding cognate
cytokine via its extracellular domain, through to its subsequent activation of
associated Janus kinases and initiation of downstream signaling pathways, as well
as the regulation of these processes. Atomic level resolution structures of TPO-R
have remained elusive. The identification of disease-causing mutations in the
receptor has, however, offered some insight into structure and function
relationships, as has artificial means of receptor activation, through TPO
mimetics, transmembrane-targeting receptor agonists, and engineering in
dimerization domains. More recently, a novel activation mechanism was identified
whereby mutated forms of calreticulin form complexes with TPO-R via its
extracellular N-glycosylated domain. Such complexes traffic pathologically in the
cell and persistently activate JAK2, downstream signal transducers and activators
of transcription (STATs), and other pathways. This pathologic TPO-R activation is
associated with a large fraction of human myeloproliferative neoplasms.
PMID- 28408902
TI - The Naturally Occurring Host Defense Peptide, LL-37, and Its Truncated Mimetics
KE-18 and KR-12 Have Selected Biocidal and Antibiofilm Activities Against Candida
albicans, Staphylococcus aureus, and Escherichia coli In vitro.
AB - Amongst the recognized classes of naturally occurring antimicrobials, human host
defense peptides are an important group with an advantage (given their source)
that they should be readily translatable to medicinal products. It is also
plausible that truncated versions will display some of the biological activities
of the parent peptide, with the benefit that they are less costly to synthesize
using solid-phase chemistry. The host defense peptide, LL-37, and two truncated
mimetics, KE-18 and KR-12, were tested for their inhibitory effects and
antibiofilm properties against Candida albicans, Staphylococcus aureus, and
Escherichia coli, microorganisms commonly implicated in biofilm-related
infections such as ventilator-associated pneumonia (VAP). Using in silico
prediction tools, the truncated peptides KE-18 and KR-12 were selected for
minimum inhibitory concentration (MIC) and antibiofilm testing on the basis of
their favorable cationicity, hydrophobic ratio, and amphipathicity compared with
the parent peptide. Two methods were analyzed for determining peptide efficacy
against biofilms; a crystal violet assay and an XTT [2,3-bis-(2-methoxy-4-nitro-5
sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. The biocidal activities
(measured by MIC) and antibiofilm activities (measured by a crystal violet assay)
appeared to be independent. LL-37 had no biocidal action against C. albicans (MIC
> 250 MUg/ml) but significant effects in both biofilm-prevention and biofilm
inhibition assays. KE-18 and KR-12 yielded superior MIC values against all three
microorganisms. Only KE-18 had a significant effect in the biofilm-prevention
assay, which persisted even at sub-MICs. Neither of the truncated peptides were
active in the biofilm-inhibition assay. KE-18 was shown to bind
lipopolysaccharide as effectively as LL-37 and to bind lipoteichoic acid more
effectively. None of the peptides showed hemolytic activity against human
erythrocytes at the concentrations tested. KE-18 should be considered for further
development as a natural peptide-derived therapeutic for prevention of multi
species biofilm-related infections such as VAP.
PMID- 28408903
TI - Anti-bacterial and Anti-biofilm Evaluation of Thiazolopyrimidinone Derivatives
Targeting the Histidine Kinase YycG Protein of Staphylococcus epidermidis.
AB - Staphylococcus epidermidis is one of the most important opportunistic pathogens
in nosocomial infections. The main pathogenicity associated with S. epidermidis
involves the formation of biofilms on implanted medical devices, biofilms
dramatically decrease the efficacy of conventional antibiotics and the host
immune system. This emphasizes the urgent need for designing novel anti
staphylococcal biofilm agents. Based on the findings that compound 5, targeting
the histidine kinase domain of S. epidermidis YycG, possessed bactericidal
activity against staphylococci, 39 derivatives of compound 5 with intact
thiazolopyrimidinone core structures were newly designed, 7 derivatives were
further screened to explore their anti-bacterial and anti-biofilm activities. The
seven derivatives strongly inhibited the growth of S. epidermidis and
Staphylococcus aureus in the minimal inhibitory concentration range of 1.56-6.25
MUM. All the derivatives reduced the proportion of viable cells in mature
biofilms. They all displayed low cytotoxicity on mammalian cells and were not
hemolytic to human erythrocytes. The biofilm inhibition activities of four
derivatives (H5-32, H5-33, H5-34, and H5-35) were further investigated under
shearing forces, they all led to significant decreases in the biofilm formation
of S. epidermidis. These results were suggestive that the seven derivatives of
compound 5 have the potential to be developed into agents for eradicating biofilm
associated infections.
PMID- 28408904
TI - Occurrence of Enterocytozoon bieneusi in Donkeys (Equus asinus) in China: A
Public Health Concern.
AB - Enterocytozoon bieneusi is an important zoonotic parasite. It can infect
virtually all animal species and has a global distribution. However, the
prevalence of E. bieneusi in donkeys (Equus asinus) has only been reported in
Algeria and Spain, and no information is available concerning genotypes of E.
bieneusi in donkeys worldwide. In the present study, a total of 301 donkey fecal
samples (48 from Jilin Province, 224 from Shandong Province and 29 from Liaoning
Province) were collected and examined by PCR amplification of the internal
transcribed spacer (ITS) region. The overall E. bieneusi prevalence was 5.3%
(16/301), with 6.3% (3/48) in Jilin Province, 4.9% (11/224) in Shandong Province,
and 6.9% (2/29) in Liaoning Province. Prevalence in different age groups ranged
from 4.2 to 5.5%. E. bieneusi prevalence in donkeys sampled in different seasons
varied from 4.2 to 6.5%. Altogether, four E. bieneusi genotypes were identified
in this study, with two known genotypes (J and D) and two novel genotypes (NCD
1and NCD-2). Phylogenetic analysis revealed that genotypes D, NCD-1 and NCD-2
belonged to group 1, while the remaining genotype J was clustered into group 2.
These findings revealed the occurrence of E. bieneusi in donkeys in China for the
first time. Moreover, the present study also firstly genotyped the E. bieneusi in
donkeys worldwide. These findings extend the distribution of E. bieneusi
genotypes and provide baseline data for controlling E. bieneusi infection in
donkeys, other animals and humans.
PMID- 28408905
TI - TET Methylcytosine Oxidases in T Cell and B Cell Development and Function.
AB - DNA methylation is established by DNA methyltransferases and is a key epigenetic
mark. Ten-eleven translocation (TET) proteins are enzymes that oxidize 5
methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidization
products (oxi-mCs), which indirectly promote DNA demethylation. Here, we provide
an overview of the effect of TET proteins and altered DNA modification status in
T and B cell development and function. We summarize current advances in our
understanding of the role of TET proteins and 5hmC in T and B cells in both
physiological and pathological contexts. We describe how TET proteins and 5hmC
regulate DNA modification, chromatin accessibility, gene expression, and
transcriptional networks and discuss potential underlying mechanisms and open
questions in the field.
PMID- 28408908
TI - Editorial: Understanding Crohn's Disease: Immunity, Genes and Microbes.
PMID- 28408907
TI - Type I Interferons and Natural Killer Cell Regulation in Cancer.
AB - Type I interferons (IFNs) are known to mediate antitumor effects against several
tumor types and have therefore been commonly used in clinical anticancer
treatment. However, how IFN signaling exerts its beneficial effects is only
partially understood. The clinically relevant activity of type I IFNs has been
mainly attributed to their role in tumor immune surveillance. Different
mechanisms have been postulated to explain how type I IFNs stimulate the immune
system. On the one hand, they modulate innate immune cell subsets such as natural
killer (NK) cells. On the other hand, type I IFNs also influence adaptive immune
responses. Here, we review evidence for the impact of type I IFNs on immune
surveillance against cancer and highlight the role of NK cells therein.
PMID- 28408906
TI - Cellular and Molecular Dynamics of Th17 Differentiation and its Developmental
Plasticity in the Intestinal Immune Response.
AB - After emerging from the thymus, naive CD4 T cells circulate through secondary
lymphoid tissues, including gut-associated lymphoid tissue of the intestine. The
activation of naive CD4 T cells by antigen-presenting cells offering cognate
antigen initiate differentiation programs that lead to the development of highly
specialized T helper (Th) cell lineages. Although initially believed that
developmental programing of effector T cells such as T helper 1 (Th1) or T helper
2 (Th2) resulted in irreversible commitment to a fixed fate, subsequent studies
have demonstrated greater flexibility, or plasticity, in effector T cell
stability than originally conceived. This is particularly so for the Th17 subset,
differentiation of which is a highly dynamic process with overlapping
developmental axes with inducible regulatory T (iTreg), T helper 22 (Th22), and
Th1 cells. Accordingly, intermediary stages of Th17 cells are found in various
tissues, which co-express lineage-specific transcription factor(s) or cytokine(s)
of developmentally related CD4 T cell subsets. A highly specialized tissue like
that of the intestine, which harbors the largest immune compartment of the body,
adds several layers of complexity to the intricate process of Th differentiation.
Due to constant exposure to millions of commensal microbes and periodic exposure
to pathogens, the intestinal mucosa maintains a delicate balance between
regulatory and effector T cells. It is becoming increasingly clear that
equilibrium between tolerogenic and inflammatory axes is maintained in the
intestine by shuttling the flexible genetic programming of a developing CD4 T
cell along the developmental axis of iTreg, Th17, Th22, and Th1 subsets.
Currently, Th17 plasticity remains an unresolved concern in the field of clinical
research as targeting Th17 cells to cure immune-mediated disease might also
target its related subsets. In this review, we discuss the expanding sphere of
Th17 plasticity through its shared developmental axes with related cellular
subsets such as Th22, Th1, and iTreg in the context of intestinal inflammation
and also examine the molecular and epigenetic features of Th17 cells that mediate
these overlapping developmental programs.
PMID- 28408910
TI - New Hypervariable SSR Markers for Diversity Analysis, Hybrid Purity Testing and
Trait Mapping in Pigeonpea [Cajanus cajan (L.) Millspaugh].
AB - Draft genome sequence in pigeonpea offers unprecedented opportunities for
genomics assisted crop improvement via enabling access to genome-wide genetic
markers. In the present study, 421 hypervariable simple sequence repeat (SSR)
markers from the pigeonpea genome were screened on a panel of eight pigeonpea
genotypes yielding marker validation and polymorphism percentages of 95.24 and
54.11%, respectively. The SSR marker assay uncovered a total of 570 alleles with
three as an average number of alleles per marker. Similarly, the mean values for
gene diversity and PIC were 0.44 and 0.37, respectively. The number of
polymorphic markers ranged from 39 to 89 for different parental combinations.
Further, 60 of these SSRs were assayed on 94 genotypes, and model based
clustering using STRUCTURE resulted in the identification of the two
subpopulations (K = 2). This remained in close agreement with the clustering
patterns inferred from genetic distance (GD)-based approaches i.e., dendrogram,
factorial and principal coordinate analysis (PCoA). The AMOVA accounted majority
of the genetic variation within groups (89%) in comparison to the variation
existing between the groups (11%). A subset of these markers was implicated for
hybrid purity testing. We also demonstrated utility of these SSR markers in trait
mapping through association and bi-parental linkage analyses. The general linear
(GLM) and mixed linear (MLM) models both detected a single SSR marker (CcGM03681)
with R2 = 16.4 as associated with the resistance to Fusarium wilt variant 2.
Similarly, by using SSR data in a segregating backcross population, the
corresponding restorer-of-fertility (Rf) locus was putatively mapped at 39 cM
with the marker CcGM08896. However, The marker-trait associations (MTAs) detected
here represent a very preliminary type and hence demand deeper investigations for
conclusive evidence. Given their ability to reveal polymorphism in simple agarose
gels, the hypervariable SSRs are valuable genomic resource for pigeonpea research
community, particularly in South Asia and East Africa where pigeonpea is
primarily grown.
PMID- 28408912
TI - Potential of Native Rhizobia in Enhancing Nitrogen Fixation and Yields of
Climbing Beans (Phaseolus vulgaris L.) in Contrasting Environments of Eastern
Kenya.
AB - Climbing bean (Phaseolus vulgaris L.) production in Kenya is greatly undermined
by low soil fertility, especially in agriculturally prolific areas. The use of
effective native rhizobia inoculants to promote nitrogen fixation could be
beneficial in climbing bean production. In this study, we carried out greenhouse
and field experiments to evaluate symbiotic efficiency, compare the effect of
native rhizobia and commercial inoculant on nodulation, growth and yield
parameters of mid-altitude climbing bean (MAC 13 and MAC 64) varieties. The
greenhouse experiment included nine native rhizobia isolates, a consortium of
native isolates, commercial inoculant Biofix, a mixture of native isolates +
Biofix, nitrogen treated control and a non-inoculated control. In the field
experiments, the treatments included the best effective native rhizobia isolate
ELM3, a consortium of native isolates, a commercial inoculant Biofix, a mixture
of native isolates + Biofix, and a non-inoculated control. Remarkably, four
native rhizobia isolates ELM3, ELM4, ELM5, and ELM8 showed higher symbiotic
efficiencies compared to the Biofix. Interestingly, there was no significant
difference in symbiotic efficiency between the two climbing bean varieties. Field
results demonstrated a significant improvement in nodule dry weight and seed
yields of MAC 13 and MAC 64 climbing bean varieties upon rhizobia inoculation
when compared to the non-inoculated controls. Inoculation with ELM3 isolate
resulted to the highest seed yield of 4,397.75 kg ha-1, indicating 89% increase
over non-inoculated control (2,334.81 kg ha-1) and 30% increase over Biofix
(3,698.79 kg ha-1). Farm site significantly influenced nodule dry weight and seed
yields. This study, therefore, revealed the potential of native rhizobia isolates
to enhance delivery of agroecosystem services including nitrogen fixation and
bean production. Further characterization and mapping of the native isolates will
be imperative in development of effective and affordable commercial inoculants.
PMID- 28408909
TI - The Maternal Diet, Gut Bacteria, and Bacterial Metabolites during Pregnancy
Influence Offspring Asthma.
AB - This review focuses on the current evidence that maternal dietary and gut
bacterial exposures during pregnancy influence the developing fetal immune system
and subsequent offspring asthma. Part 1 addresses exposure to a farm environment,
antibiotics, and prebiotic and probiotic supplementation that together indicate
the importance of bacterial experience in immune programming and offspring
asthma. Part 2 outlines proposed mechanisms to explain these associations
including bacterial exposure of the fetoplacental unit; immunoglobulin-related
transplacental transport of gut bacterial components; cytokine signaling
producing fetomaternal immune alignment; and immune programming via metabolites
produced by gut bacteria. Part 3 focuses on the interplay between diet, gut
bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial
composition, with dietary microbiota-accessible carbohydrates (MACs) selecting
short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse
models indicates an association between increased maternal dietary MACs, SCFA
exposure during pregnancy, and reduced offspring asthma that is, at least in
part, mediated by the induction of regulatory T lymphocytes in the fetal lung.
Part 4 discusses considerations for future studies investigating maternal diet-by
microbiome determinants of offspring asthma including the challenge of measuring
dietary MAC intake; limitations of the existing measures of the gut microbiome
composition and metabolic activity; measures of SCFA exposure; and the
complexities of childhood respiratory health assessment.
PMID- 28408911
TI - Metabolic Adaptation, a Specialized Leaf Organ Structure and Vascular Responses
to Diurnal N2 Fixation by Nostoc azollae Sustain the Astonishing Productivity of
Azolla Ferns without Nitrogen Fertilizer.
AB - Sustainable agriculture demands reduced input of man-made nitrogen (N)
fertilizer, yet N2 fixation limits the productivity of crops with heterotrophic
diazotrophic bacterial symbionts. We investigated floating ferns from the genus
Azolla that host phototrophic diazotrophic Nostoc azollae in leaf pockets and
belong to the fastest growing plants. Experimental production reported here
demonstrated N-fertilizer independent production of nitrogen-rich biomass with an
annual yield potential per ha of 1200 kg-1 N fixed and 35 t dry biomass. 15N2
fixation peaked at noon, reaching 0.4 mg N g-1 dry weight h-1. Azolla ferns
therefore merit consideration as protein crops in spite of the fact that little
is known about the fern's physiology to enable domestication. To gain an
understanding of their nitrogen physiology, analyses of fern diel transcript
profiles under differing nitrogen fertilizer regimes were combined with
microscopic observations. Results established that the ferns adapted to the
phototrophic N2-fixing symbionts N. azollae by (1) adjusting metabolically to
nightly absence of N supply using responses ancestral to ferns and seed plants;
(2) developing a specialized xylem-rich vasculature surrounding the leaf-pocket
organ; (3) responding to N-supply by controlling transcripts of genes mediating
nutrient transport, allocation and vasculature development. Unlike other non-seed
plants, the Azolla fern clock is shown to contain both the morning and evening
loops; the evening loop is known to control rhythmic gene expression in the
vasculature of seed plants and therefore may have evolved along with the
vasculature in the ancestor of ferns and seed plants.
PMID- 28408913
TI - Altered Expression of Genes Implicated in Xylan Biosynthesis Affects Penetration
Resistance against Powdery Mildew.
AB - Heteroxylan has recently been identified as an important component of papillae,
which are formed during powdery mildew infection of barley leaves. Deposition of
heteroxylan near the sites of attempted fungal penetration in the epidermal cell
wall is believed to enhance the physical resistance to the fungal penetration peg
and hence to improve pre-invasion resistance. Several glycosyltransferase (GT)
families are implicated in the assembly of heteroxylan in the plant cell wall,
and are likely to work together in a multi-enzyme complex. Members of key GT
families reported to be involved in heteroxylan biosynthesis are up-regulated in
the epidermal layer of barley leaves during powdery mildew infection. Modulation
of their expression leads to altered susceptibility levels, suggesting that these
genes are important for penetration resistance. The highest level of resistance
was achieved when a GT43 gene was co-expressed with a GT47 candidate gene, both
of which have been predicted to be involved in xylan backbone biosynthesis.
Altering the expression level of several candidate heteroxylan synthesis genes
can significantly alter disease susceptibility. This is predicted to occur
through changes in the amount and structure of heteroxylan in barley papillae.
PMID- 28408914
TI - Transcriptome Analysis Reveals Candidate Genes Related to Color Fading of 'Red
Bartlett' (Pyrus communis L.).
AB - The red color of fruit is an attractive plant trait for consumers. Plants with
color-faded fruit have a lower commercial value, such as 'Red Bartlett' pears
(Pyrus communis L.) that have dark-red fruit in the early stages of fruit
development that subsequently fade to red-green at maturity. To identify the
reason for color fading, we first analyzed the anthocyanin content of peel from
'Red Bartlett,' which displays the color fading phenomenon, and 'Starkrimson,'
which has no color fading. Results showed that the anthocyanin content of 'Red
Bartlett' peel decreased significantly late in fruit development, while in
'Starkrimson' there was no significant decrease. Next, RNA-Sequencing was used to
identify 947 differentially expressed genes (DEGs) between 'Red Bartlett' and
'Starkrimson.' Among them, 471 genes were upregulated and 476 genes were
downregulated in 'Red Bartlett' at the late development stage relative to
'Starkrimson.' During 'Red Bartlett' color fading, the structural gene LDOX and
six GST family genes were downregulated, while FLS, LAC, POD, and five light
responding genes were significantly upregulated. Additionally, 45 genes encoding
transcription factors MYB, bHLH, WRKY, NAC, ERF, and zinc finger were identified
among 947 DEGs. Changes in the expression of these genes may be responsible for
the decrease in anthocyanin accumulation in 'Red Bartlett' fruit. Taken together,
this study demonstrated that color fading of 'Red Bartlett' was closely linked to
reduced anthocyanin biosynthesis, increased anthocyanin degradation and
suppression of anthocyanin transport. It also provided novel evidence for the
involvement of light signals in the color fading of red-skinned pears.
PMID- 28408915
TI - Tomato Transcription Factor SlWUS Plays an Important Role in Tomato Flower and
Locule Development.
AB - Tomato is a model species for fleshy fruit development. The shapes and sizes of
tomato (Solanum lycopersicum L.) are mainly controlled by several loci, including
locule number (lc). Two single nucleotide polymorphisms were found downstream of
WUSCHEL (SlWUS) in a putative tomato CArG cis-regulatory element. The lc mutation
may affect the binding of AGAMOUS(AG), cause the up-regulation of SlWUS and
result in increased locule numbers. In this study, tissue expression levels
showed that SlWUS is expressed in young floral buds and shoot apexes. Silencing
SlWUS on an lc mutant genetic background with an RNA interference (RNAi) strategy
resulted in smaller flowers and fruit than those of the wild-type plants, with
decreased locule number. Further study revealed that the SlWUS RNAi lines
exhibited altered expression levels of the TAG1 and SlCLV3 genes that participate
in the regulation of tomato flower and fruit locule development. In conclusion,
this study provides the first genetic evidence that SlWUS may be the candidate
gene of the lc locus and reveals the function of SlWUS in flower development.
PMID- 28408916
TI - 1-Aminocyclopropane-1-Carboxylate Oxidase Induction in Tomato Flower Pedicel
Phloem and Abscission Related Processes Are Differentially Sensitive to Ethylene.
AB - Ethylene has impact on several physiological plant processes, including
abscission, during which plants shed both their vegetative and reproductive
organs. Cell separation and programmed cell death are involved in abscission, and
these have also been correlated with ethylene action. However, the detailed
spatiotemporal pattern of the molecular events during abscission remains unknown.
We examined the expression of two tomato ACO genes, LeACO1, and LeACO4 that
encode the last enzyme in ethylene biosynthesis, 1-aminocyclopropane-1
carboxylate oxidase (ACO), together with the expression of other abscission
associated genes involved in cell separation and programmed cell death, during a
period of 0-12 h after abscission induction in the tomato flower pedicel
abscission zone and nearby tissues. In addition, we determined their localization
in specific cell layers of the flower pedicel abscission zone and nearby tissues
obtained by laser microdissection before and 8 h after abscission induction. The
expression of both ACO genes was localized to the vascular tissues in the
pedicel. While LeACO4 was more uniformly expressed in all examined cell layers,
the main expression site of LeACO1 was in cell layers just outside the abscission
zone in its proximal and distal part. We showed that after abscission induction,
ACO1 protein was synthesized in phloem companion cells, in which it was localized
mainly in the cytoplasm. Samples were additionally treated with 1
methylcyclopropene (1-MCP), a competitive inhibitor of ethylene actions, and
analyzed 8 h after abscission induction. Cell-layer-specific changes in gene
expression were observed together with the specific localization and ethylene
sensitivity of the hallmarks of cell separation and programmed cell death. While
treatment with 1-MCP prevented separation of cells through inhibition of the
expression of polygalacturonases, which are the key enzymes involved in
degradation of the middle lamella, this had less impact on the occurrence of
different kinds of membrane vesicles and abscission-related programmed cell
death. In the flower pedicel abscission zone, the physical progressions of cell
separation and programmed cell death are perpendicular to each other and start in
the vascular tissues.
PMID- 28408917
TI - High Level of Nitrogen Makes Tomato Plants Releasing Less Volatiles and
Attracting More Bemisia tabaci (Hemiptera: Aleyrodidae).
AB - Tomato (Solanum lycopersicum) production is seriously hampered by the infestation
of the sweetpotato whitefly, Bemisia tabaci MEAM 1 (Middle East-Asia Minor 1).
The infestation behavior of the whiteflies could be affected by the quantity of
plant released volatile organic compounds (VOCs) related to nitrogen
concentrations of the plant. In this study, we determined the infestation
behavior of B. tabaci to the tomato plants that produced different levels of VOCs
after application of different levels of nitrogen with a wind tunnel and an
olfactometer. We also analyzed the VOCs released from nitrogen-treated tomato
plants using solid phase microextraction and gas chromatography-mass
spectrometry. The results revealed that the production of eight VOCs (beta
pinene, (+)-4-carene, alpha-terpinene, p-cymene, beta-phellandrene, alpha
copaene, beta-caryophyllene, and alpha-humulene) was reduced after the plants
were treated with high levels of nitrogen. However, more whiteflies were
attracted to the tomato plants treated with high levels of nitrogen than to the
plants treated with normal or below normal levels of nitrogen. These results
clearly indicated that nitrogen can change the quality and quantity of tomato
plant volatile chemicals, which play important roles in B. tabaci host plant
selection.
PMID- 28408918
TI - CFTR Gene Mutations in the Egyptian Population: Current and Future Insights for
Genetic Screening Strategy.
PMID- 28408919
TI - Transcatheter aortic valve implantation: a revolution in the therapy of elderly
and high-risk patients with severe aortic stenosis.
AB - Transcatheter aortic valve implantation (TAVI) represents a real revolution in
the field of interventional cardiology for the treatment of elderly or high-risk
surgical patients with severe symptomatic aortic valve stenosis. Today, TAVI
seems to play a key and a reliable role in the treatment of intermediate and
maybe low-risk patients with severe aortic stenosis. TAVI has also evolved from a
complex and hazardous procedure into an effective and safe therapy by the
development of new generation devices. This article aims to review the background
and future of TAVI, clinical trials and registries with old and new generation
TAVI devices and to focus on some open issues related to post-procedural
outcomes.
PMID- 28408920
TI - Endoscopic-assisted linea alba reconstruction: New technique for treatment of
symptomatic umbilical, trocar, and/or epigastric hernias with concomitant rectus
abdominis diastasis.
AB - BACKGROUND: Patients with symptomatic umbilical, trocar, and/or epigastric
hernias and concomitant rectus abdominis diastasis represent a growing clinical
problem. The optimal management of this complex hernia situation is the subject
of debate in the literature. This paper reports the early results of an
innovative surgical technique aimed at managing this hernia situation. METHODS:
Endoscopic-assisted linea alba reconstruction (ELAR) with mesh augmentation is a
surgical technique long known in the literature for its good outcome for
incisional hernia repair (myofascial release, overlapping herniorrhaphy, Gibson's
operation, shoelace repair, anterior rectus sheath repair, dynamic patch plasty)
via a small access route. The early results for 140 patients are presented here.
RESULTS: Two patients (1.4%) developed postoperative complications requiring redo
surgery. These were two cases of diffuse secondary bleeding without an
identifiable bleeding source, in one patient with liver cirrhosis and portal
hypertension and in another patient receiving treatment with platelet aggregation
inhibitors. All other complications were successively managed with conservative
treatment. After 1 year, two of 30 patients reported occasional pain, including
pain at rest in one patient. CONCLUSION: The ELAR technique with mesh
augmentation is an innovative, minimally invasive surgical procedure for
treatment of patients with a complex abdominal wall hernia comprising symptomatic
umbilical, trocar, and/or epigastric hernias with concomitant rectus abdominis
diastasis.
PMID- 28408921
TI - Phase Segmentation Methods for an Automatic Surgical Workflow Analysis.
AB - In this paper, we present robust methods for automatically segmenting phases in a
specified surgical workflow by using latent Dirichlet allocation (LDA) and hidden
Markov model (HMM) approaches. More specifically, our goal is to output an
appropriate phase label for each given time point of a surgical workflow in an
operating room. The fundamental idea behind our work lies in constructing an HMM
based on observed values obtained via an LDA topic model covering optical flow
motion features of general working contexts, including medical staff, equipment,
and materials. We have an awareness of such working contexts by using multiple
synchronized cameras to capture the surgical workflow. Further, we validate the
robustness of our methods by conducting experiments involving up to 12 phases of
surgical workflows with the average length of each surgical workflow being 12.8
minutes. The maximum average accuracy achieved after applying leave-one-out cross
validation was 84.4%, which we found to be a very promising result.
PMID- 28408922
TI - A Novel Histogram Region Merging Based Multithreshold Segmentation Algorithm for
MR Brain Images.
AB - Multithreshold segmentation algorithm is time-consuming, and the time complexity
will increase exponentially with the increase of thresholds. In order to reduce
the time complexity, a novel multithreshold segmentation algorithm is proposed in
this paper. First, all gray levels are used as thresholds, so the histogram of
the original image is divided into 256 small regions, and each region corresponds
to one gray level. Then, two adjacent regions are merged in each iteration by a
new designed scheme, and a threshold is removed each time. To improve the
accuracy of the merger operation, variance and probability are used as energy. No
matter how many the thresholds are, the time complexity of the algorithm is
stable at O(L). Finally, the experiment is conducted on many MR brain images to
verify the performance of the proposed algorithm. Experiment results show that
our method can reduce the running time effectively and obtain segmentation
results with high accuracy.
PMID- 28408923
TI - Novel Methods for Measuring Depth of Anesthesia by Quantifying Dominant
Information Flow in Multichannel EEGs.
AB - In this paper, we propose novel methods for measuring depth of anesthesia (DOA)
by quantifying dominant information flow in multichannel EEGs. Conventional
methods mainly use few EEG channels independently and most of multichannel EEG
based studies are limited to specific regions of the brain. Therefore the
function of the cerebral cortex over wide brain regions is hardly reflected in
DOA measurement. Here, DOA is measured by the quantification of dominant
information flow obtained from principle bipartition. Three bipartitioning
methods are used to detect the dominant information flow in entire EEG channels
and the dominant information flow is quantified by calculating information
entropy. High correlation between the proposed measures and the plasma
concentration of propofol is confirmed from the experimental results of clinical
data in 39 subjects. To illustrate the performance of the proposed methods more
easily we present the results for multichannel EEG on a two-dimensional (2D)
brain map.
PMID- 28408924
TI - Investigation of Small Bowel Abnormalities in HIV-Infected Patients Using Capsule
Endoscopy.
AB - HIV infection is reportedly associated with an increased permeability of the
intestinal epithelium and can cause HIV enteropathy, which occurs independently
of opportunistic infections. However, the characteristics of small bowel
abnormalities attributable to HIV infection are rarely investigated. In the
present study, we assessed the intestinal mucosal changes found in HIV-infected
patients and compared them with the mucosa of healthy control subjects using
capsule endoscopy (CE). Three of the 27 HIV-infected patients harbored
gastrointestinal opportunistic infections and were thus excluded from subsequent
analyses. The endoscopic findings of CE in HIV-infected patients were
significantly higher than those in control subjects (55% versus 10%, P = 0.002);
however, most lesions, such as red spots or tiny erosions, were unlikely to cause
abdominal symptoms. After validating the efficacy of CE for the diagnosis of
villous atrophy, we found that the prevalence of villous atrophy was 54% (13/24)
among HIV-infected patients. Interestingly, villous atrophy persisted in patients
receiving long-term antiretroviral therapy, though most of them exhibited
reconstituted peripheral blood CD4+ T cells. Although we could not draw any
conclusions regarding the development of small bowel abnormalities in HIV
infected patients, our results may provide some insight regarding the
pathogenesis of HIV enteropathy.
PMID- 28408925
TI - Combination Therapy with a Sodium-Glucose Cotransporter 2 Inhibitor and a
Dipeptidyl Peptidase-4 Inhibitor Additively Suppresses Macrophage Foam Cell
Formation and Atherosclerosis in Diabetic Mice.
AB - Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their
antihyperglycemic roles, have antiatherosclerotic effects. We reported that
sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a
glucose-dependent manner in diabetic mice. Here, we investigated the effects of
combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice.
SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day),
either alone or in combination, were administered to db/db mice or streptozotocin
induced diabetic apolipoprotein E-null (Apoe-/- ) mice. Ipragliflozin and
alogliptin monotherapies improved glucose intolerance; however, combination
therapy did not show further improvement. The foam cell formation of peritoneal
macrophages was suppressed by both the ipragliflozin and alogliptin monotherapies
and was further enhanced by combination therapy. Although foam cell formation was
closely associated with HbA1c levels in all groups, DPP-4i alone or the
combination group showed further suppression of foam cell formation compared with
the control or SGLT2i group at corresponding HbA1c levels. Both ipragliflozin and
alogliptin monotherapies decreased scavenger receptors and increased cholesterol
efflux regulatory genes in peritoneal macrophages, and combination therapy showed
additive changes. In diabetic Apoe-/- mice, combination therapy showed the
greatest suppression of plaque volume in the aortic root. In conclusion,
combination therapy with SGLT2i and DPP4i synergistically suppresses macrophage
foam cell formation and atherosclerosis in diabetic mice.
PMID- 28408927
TI - Activities of Amphioxus GH-Like Protein in Osmoregulation: Insight into Origin of
Vertebrate GH Family.
AB - GH is known to play an important role in both growth promotion and osmoregulation
in vertebrates. We have shown that amphioxus possesses a single GH-like hormone
(GHl) gene encoding a functional protein capable of promoting growth. However, if
GHl can mediate osmoregulation remains open. Here, we demonstrated clearly that
GHl increased not only the survival rate of amphioxus but also the muscle
moisture under high salinity. Moreover, GHl induced the expression of both the
ion transporter Na+-K+-ATPase (NKA) and Na+-K+-2Cl- cotransporter (NKCC) in the
gill as well as the mediator of GH action IGFl in the hepatic caecum, indicating
that GHl fulfills this osmoregulatory activity through the same mechanisms of
vertebrate GH. These results together suggest that the osmoregulatory activities
of GH had emerged in the basal chordate amphioxus. We also proposed a new model
depicting the origin of pituitary hormone family in vertebrates.
PMID- 28408926
TI - Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and
Treatment of Testosterone Deficiency in Bone Health.
AB - It is well recognized that bone loss accelerates in hypogonadal states, with
female menopause being the classic example of sex hormones affecting the
regulation of bone metabolism. Underrepresented is our knowledge of the clinical
and metabolic consequences of overt male hypogonadism, as well as the more subtle
age-related decline in testosterone on bone quality. While menopause and estrogen
deficiency are well-known risk factors for osteoporosis in women, the effects of
age-related testosterone decline in men on bone health are less well known. Much
of our knowledge comes from observational studies and retrospective analysis on
small groups of men with variable causes of primary or secondary hypogonadism and
mild to overt testosterone deficiencies. This review aims to present the current
knowledge of the consequences of adult male hypogonadism on bone metabolism. The
direct and indirect effects of testosterone on bone cells will be explored as
well as the important differences in male osteoporosis and assessment as compared
to that in females. The clinical consequence of both primary and secondary
hypogonadism, as well as testosterone decline in older males, on bone density and
fracture risk in men will be summarized. Finally, the therapeutic options and
their efficacy in male osteoporosis and hypogonadism will be discussed.
PMID- 28408928
TI - Salivary Alpha-Amylase Enzyme, Psychological Disorders, and Life Quality in
Patients with Recurrent Aphthous Stomatitis.
AB - Objective. The aim of this study was to evaluate stress, anxiety, and salivary
alpha-amylase (SAA) activity in patients with recurrent aphthous stomatitis
(RAS). The impact of this disease on the life quality was also evaluated. Design.
Twenty-two patients with RAS and controls, matched by sex and age, were selected.
Stress and anxiety were assessed using Lipp's Inventory of Stress Symptoms and
Beck Anxiety Inventory. Life quality was assessed through the World Health
Organization Quality of Life-bref (WHOQOL-BREF) and the Oral Health Impact
Profile-14 (OHIP-14). Saliva samples were collected in the morning and afternoon
and the SAA activity was analyzed by enzymatic kinetic method. Results. No
significant difference was observed between the groups regarding the SAA activity
(p = 0.306). Patients with RAS had higher scores of anxiety (p = 0.016). The
scores of WHOQOL-BREF were significantly lower in patients with RAS. The values
obtained through OHIP-14 were significantly higher in these patients (p = 0.002).
Conclusion. RAS negatively affects the life quality. Patients with the disease
have higher levels of anxiety, suggesting its association with the
etiopathogenesis of RAS.
PMID- 28408929
TI - Detection of Cu2+ in Water Based on Histidine-Gold Labeled Multiwalled Carbon
Nanotube Electrochemical Sensor.
AB - Based on the strong interaction between histidine and copper ions and the signal
enhancement effect of gold-labeling carbon nanotubes, an electrochemical sensor
is established and used to measure copper ions in river water. In this study the
results show that the concentrations of copper ion have well linear relationship
with the peak current in the range of 10-11-10-7 mol/L, and the limit of
detection is 10-12 mol/L. When using this method to detect copper ions in the
Xiangjiang River, the test results are consistent with the atomic absorption
method. This study shows that the sensor is convenient to be used in daily
monitoring of copper ions in river water.
PMID- 28408930
TI - A Case of Initially Undiagnosed Chikungunya Arthritis Developing into Chronic
Phase in a Nonendemic Area.
AB - This case report described a 40-year-old lady presented with fever, headache,
arthralgia, myalgia, and impaired liver function after returning from the
Philippines. Chikungunya virus (CHIKV) and dengue serology were negative. Eight
weeks after initial presentation, she experienced inflammatory polyarthritis
mimic rheumatoid arthritis. This time CHIKV-IgM was detected, together with a >4
fold rise of CHIKV-polyvalent-antibody titre. The first CHIKV-IgM negative sample
was reexamined and was CHIKV-PCR positive. CHIKV infection was confirmed and
diagnosis of CHIKV-related arthritis was made. A quarter of CHIKV infected
individuals develop post-CHIKV rheumatisms that affect quality of life and may
need treatment with Disease Modifying Antirheumatic Drugs. This case highlights
the importance of considering CHIKV infection in patients present with
symmetrical polyarthritis particularly after travel to endemic regions. Testing
of both CHIKV acute and convalescent-phase serum for CHIKV antibodies and PCR is
recommended in suspicious case.
PMID- 28408931
TI - Drug Induced Pneumonitis Secondary to Treatment with
Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK(r)) for Chronic
Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction.
AB - VIEKIRA PAK (ritonavir-boosted paritaprevir/ombitasvir and dasabuvir) is an
approved treatment for compensated patients with genotype 1 (GT1) chronic
hepatitis C virus (HCV) infection. This oral regimen has minimal adverse effects
and is well tolerated. Cure rates are 97% in patients infected with HCV GT 1a and
99% in those with HCV GT 1b. We report the first case of life-threatening
allergic pneumonitis associated with VIEKIRA PAK. This unexpected serious adverse
event occurred in a 68-year-old Chinese female with genotype 1b chronic hepatitis
C and Child-Pugh A cirrhosis. One week into treatment with VIEKIRA PAK without
ribavirin, she was admitted to hospital with respiratory distress and acute
kidney injury requiring intensive care input. She was initially diagnosed with
community acquired pneumonia and improved promptly with intravenous antibiotics
and supported care. No bacterial or viral pathogens were cultured. Following
complete recovery, she recommenced VIEKIRA PAK but represented 5 days later with
more rapidly progressive respiratory failure, requiring intubation and
ventilation, inotropic support, and haemodialysis. The final diagnosis was drug
induced pneumonitis.
PMID- 28408932
TI - Huge Lymphangioma of the Esophagus Resected by Endoscopic Piecemeal Mucosal
Resection.
AB - We present an unusual case of a 41-year-old male patient with a large
lymphangioma of the esophagus. Endoscopy revealed that the structure measured 60
* 10 mm in the mucosa and the submucosa and had a heterogenous echo pattern. The
esophageal mass was successfully resected by endoscopic piecemeal mucosal
resection. However, most esophageal lymphangiomas that are larger than 2 cm in
diameter reported in the literature can be removed only through open surgery.
Thus far, we know of no reported cases of endoscopic resection as a treatment for
this case.
PMID- 28408933
TI - Endovascular Stent Grafting for Aortic Arch Aneurysm in Aortoiliac Occlusive
Disease following Aortic Arch Debranching and Aortobifemoral Reconstruction.
AB - Treatment of thoracic aortic aneurysms constitutes high mortality and morbidity
rates despite improvements in surgery, anesthesia, and technology. Endovascular
stent grafting may be an alternative therapy with lower risks when compared with
conventional techniques. However, sometimes the branches of the aortic arch may
require transport to the proximal segments prior to successful thoracic aortic
endovascular stent grafting. Atherosclerosis is accounted among the etiology of
both aneurysms and occlusive diseases that can coexist in the same patient. In
these situations stent grafting may even be more complicated. In this report, we
present the treatment of a 92-year-old patient with aortic arch aneurysm and
proximal descending aortic aneurysm. For successful thoracic endovascular stent
grafting, the patient needed an alternative route other than the native femoral
and iliac arteries for the deployment of the stent graft. In addition,
debranching of left carotid and subclavian arteries from the aortic arch was also
required for successful exclusion of the thoracic aneurysm.
PMID- 28408934
TI - SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural
Stem/Progenitor Cells.
AB - SDF-1 and its primary receptor, CXCR4, are highly expressed in the embryonic
central nervous system (CNS) and play a crucial role in brain architecture. Loss
of SDF-1/CXCR4 signaling causes abnormal development of neural stem/progenitor
cells (NSCs/NPCs) in the cerebellum, hippocampus, and cortex. However, the
mechanism of SDF-1/CXCR4 axis in NSCs/NPCs regulation remains unknown. In this
study, we found that elimination of SDF-1/CXCR4 transduction caused NSCs/NPCs to
lose their stemness characteristics and to encounter neurogenic differentiation.
Moreover, Notch and RE1 silencing transcription factor (REST) both play an
essential role in NSCs/NPCs maintenance and neuronal differentiation and were
dramatically downregulated following SDF-1/CXCR4 cascade inhibition. Finally, we
demonstrated that the expression of achaete-scute homolog 1 (Ascl1), a proneural
gene, and p27, an antiproliferative gene, were significantly increased after
genetic elimination of SDF-1 alleles. Our results support that the loss of
functional SDF-1/CXCR4 signaling pathway in NSCs/NPCs induces exit of cell cycle
and promotes premature neural differentiation.
PMID- 28408935
TI - Socioeconomic and Racial/Ethnic Disparities in Cancer Mortality, Incidence, and
Survival in the United States, 1950-2014: Over Six Decades of Changing Patterns
and Widening Inequalities.
AB - We analyzed socioeconomic and racial/ethnic disparities in US mortality,
incidence, and survival rates from all-cancers combined and major cancers from
1950 to 2014. Census-based deprivation indices were linked to national mortality
and cancer data for area-based socioeconomic patterns in mortality, incidence,
and survival. The National Longitudinal Mortality Study was used to analyze
individual-level socioeconomic and racial/ethnic patterns in mortality. Rates,
risk-ratios, least squares, log-linear, and Cox regression were used to examine
trends and differentials. Socioeconomic patterns in all-cancer, lung, and
colorectal cancer mortality changed dramatically over time. Individuals in more
deprived areas or lower education and income groups had higher mortality and
incidence rates than their more affluent counterparts, with excess risk being
particularly marked for lung, colorectal, cervical, stomach, and liver cancer.
Education and income inequalities in mortality from all-cancers, lung, prostate,
and cervical cancer increased during 1979-2011. Socioeconomic inequalities in
cancer mortality widened as mortality in lower socioeconomic groups/areas
declined more slowly. Mortality was higher among Blacks and lower among
Asian/Pacific Islanders and Hispanics than Whites. Cancer patient survival was
significantly lower in more deprived neighborhoods and among most ethnic-minority
groups. Cancer mortality and incidence disparities may reflect inequalities in
smoking, obesity, physical inactivity, diet, alcohol use, screening, and
treatment.
PMID- 28408936
TI - Household Food Insecurity and Its Association with Nutritional Status of Children
6-59 Months of Age in East Badawacho District, South Ethiopia.
AB - Background. Ethiopia has one of the highest child malnutrition rates in the
world. Food insecurity is one of the determinant factors of malnutrition in
developing countries; however its role remains unclear. Objective. To assess
household food insecurity and its association with the nutritional status of
children 6-59 months of age in East Badawacho District, South Ethiopia. Methods.
A community based cross-sectional study was conducted from February 20 to 30,
2014 on a sample of 508 mother/child pairs of 6-59-month-old children. Sample
households with eligible children were selected using systematic random sampling
technique. Both bivariate and multivariate analysis were used to identify factors
associated with nutritional status of children. P value of <0.05 was considered
as statistically significant. Result. The prevalence of household food insecurity
was 75.8%. The prevalence rates of stunting, underweight, and wasting among
children were 45.6%, 26.3%, and 14.6%, respectively. Household food insecurity
was significantly associated with underweight (AOR = 3.82; CI = 1.78-8.19) and
stunting (AOR = 6.7; CI = 3.71-12.1) but not with wasting. Conclusion and
Recommendation. Household food insecurity and the prevalence rates of stunting,
underweight, and wasting, among children 6 to 59 months, were high. Intervention
programs should focus on improving household food insecurity and nutritional
status of children.
PMID- 28408937
TI - Detection of Gastrointestinal Pathogens from Stool Samples on Hemoccult Cards by
Multiplex PCR.
AB - Purpose. Up to 30% of international travelers are affected by travelers' diarrhea
(TD). Reliable data on the etiology of TD is lacking. Sufficient laboratory
capacity at travel destinations is often unavailable and transporting
conventional stool samples to the home country is inconvenient. We evaluated the
use of Hemoccult cards for stool sampling combined with a multiplex PCR for the
detection of model viral, bacterial, and protozoal TD pathogens. Methods.
Following the creation of serial dilutions for each model pathogen, last positive
dilution steps (LPDs) and thereof calculated last positive sample concentrations
(LPCs) were compared between conventional stool samples and card samples.
Furthermore, card samples were tested after a prolonged time interval simulating
storage during a travel duration of up to 6 weeks. Results. The LPDs/LPCs were
comparable to testing of conventional stool samples. After storage on Hemoccult
cards, the recovery rate was 97.6% for C. jejuni, 100% for E. histolytica, 97.6%
for norovirus GI, and 100% for GII. Detection of expected pathogens was possible
at weekly intervals up to 42 days. Conclusion. Stool samples on Hemoccult cards
stored at room temperature can be used in combination with a multiplex PCR as a
reliable tool for testing of TD pathogens.
PMID- 28408938
TI - Bacteraemia in Intensive Care Unit: Clinical, Bacteriological, and Prognostic
Prospective Study.
AB - Objectives. We conducted a one-year observational study from December 2012 to
November 2013 to describe the epidemiology of bacteraemia in intensive care units
(ICU) of Mohammed V Military Teaching Hospital of Rabat (Morocco). Methods. The
study consisted of monitoring all blood cultures coming from intensive care units
and studying the bacteriological profile of positive blood cultures as well as
their clinical significance. Results. During this period, a total of 46 episodes
of bacteraemia occurred, which corresponds to a rate of 15,4/1000 patients. The
rate of nosocomial infections was 97% versus 3% for community infections. The
most common source of bacteraemia was the lungs in 33%, but no source was
identified in 52% of the episodes. Gram negative organisms were isolated in 83,6%
of the cases with Acinetobacter baumannii being the most frequent. Antibiotic
resistance was very high with 42,5% of extended-spectrum beta-lactamases (ESBLs)
in Enterobacteriaceae and 100% of carbapenemase in Acinetobacter baumannii. The
antibiotherapy introduced in the first 24 hours was adequate in 72% of the cases.
Conclusions. Bloodstream infections in ICU occur most often in patients over 55
years, with hypertension and diabetes. The bacteria involved are mainly Gram
negative bacteria multiresistant to antibiotics. Early administration of
antibiotics significantly reduces patients mortality.
PMID- 28408939
TI - The Immune Effects of an African Traditional Energy Tonic in In Vitro and In Vivo
Models.
AB - Most of the African traditional medicines (ATM) are formulated as energy tonics
to boost and maintain immune defences. In this study, we aimed to evaluate the
immune effects of a traditional energy tonic using peripheral blood mononuclear
cells (PBMCs), THP-1 monocytes, and bacteria infected rats. When tested in
mitogen and peptidoglycan stimulated PBMCs, this energy tonic showed minimal
cytotoxicity, while in acute toxicity studies in rats it did not exhibit any
significant toxicity at doses up to 2000 mg/mL/kg. The energy tonic doses between
100 and 10 MUg/mL were shown to stimulate secretion of cytokines and increase sIL
2R levels in PHA-treated PBMCs. Similar doses in PG-S. aureus-stimulated PBMCs
significantly (p < 0.05) increased IL-1alpha, IL-2, and GM-CSF while causing a
significant (p < 0.05) decrease in sIL-2R levels. NF-kappabeta transcriptional
activity was increased in LPS stimulated THP-1 cells. In Sprague Dawley rats
pretreated with the energy tonic and then infected with S. aureus, there were
insignificant increases in cytokines and sIL-2R when compared to bacteria
infected only and 5% Enrofloxacin treated rats. Posttreatment with energy tonic
doses after infection with S. aureus did not enhance inflammatory cytokines
significantly but changed the immune response profile and decreased
corticosterone levels. This ATM showed promising immunomodulatory effects on
isolated immune cells and modulated the immune response of rat models infected
with S. aureus.
PMID- 28408940
TI - Laser Acupuncture Exerts Neuroprotective Effects via Regulation of Creb, Bdnf,
Bcl-2, and Bax Gene Expressions in the Hippocampus.
AB - Acupuncture has a positive effect on cognitive deficits. However, the effects of
laser acupuncture (LA) on cognitive function and its mechanisms of action are
unclear. The present study aimed to evaluate the effects of LA on middle cerebral
artery occlusion- (MCAO-) induced cognitive impairment and its mechanisms of
action. Transient focal cerebral ischemia was modeled in adult Sprague-Dawley
rats by MCAO. After LA or manual-acupuncture (MA) treatment at the GV20 and HT7
for 2 weeks, hippocampal-dependent memory was evaluated using the Morris water
maze (MWM) test. The hippocampus was dissected to analyze choline
acetyltransferase (ChAT) immunoreactivity and Creb, Bdnf, Bcl-2, and Bax gene
expressions. MWM test demonstrated a significant improvement in hippocampal
dependent memory in the MCAO rats after LA treatment. LA treatment significantly
reversed the postischemic decrease in ChAT immunoreactivity in the hippocampal
CA1 region. LA treatment significantly normalized gene expression in the
hippocampus which had been altered by MCAO, especially upregulating gene
expression of Creb, Bdnf, and Bcl-2 and downregulating gene expression of Bax.
This study suggests that LA treatment could improve cognitive impairment in MCAO
rats to enhance the cholinergic system in the hippocampal CA1 region and to exert
a neuroprotective effect by regulating Creb, Bdnf, Bcl-2, and Bax gene
expressions.
PMID- 28408941
TI - Clinical Evaluation of Acupuncture as Treatment for Complications of
Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor
Blind Trial.
AB - Background and Purpose. The effect of acupuncture as treatment for poststroke
complications is questionable. We performed a randomized, sham-controlled double
blind study to investigate it. Methods. Patients with first-time acute stroke
were randomized to receive 24 sessions of either real or sham acupuncture during
an eight-week period. The primary outcome measure was change in National
Institute of Health Stroke Scale (NIHSS) score. Secondary outcome measures
included changes in Barthel Index (BI), Instrumental Activities of Daily Living
(IADL), Hamilton Depression Rating Scale (HAM-D), and Visual Analogue Scale (VAS)
for pain scores. Results. Of the 52 patients who were randomized to receive
acupuncture (n = 28) or placebo (n = 24), 10 patients in the acupuncture group
and 9 patients in the placebo group failed to complete the treatment. In total,
18 patients in the acupuncture group and 15 patients in the control group
completed the treatment course. Reduction in pain was significantly greater in
the acupuncture group than in the control group (p value = 0.04). There were no
significant differences in the other measures between the two groups.
Conclusions. Acupuncture provided more effective poststroke pain relief than sham
acupuncture treatment. However, acupuncture had no better effect on neurological,
functional, and psychological improvement.
PMID- 28408942
TI - Identification of Tengfu Jiangya Tablet Target Biomarkers with Quantitative
Proteomic Technique.
AB - Tengfu Jiangya Tablet (TJT) is a well accepted antihypertension drug in China and
its major active components were Uncaria total alkaloids and Semen Raphani
soluble alkaloid. To further explore treatment effects mechanism of TJT on
essential hypertension, a serum proteomic study was performed. Potential
biomarkers were quantified in serum of hypertension individuals before and after
taking TJT with isobaric tags for relative and absolute quantitation (iTRAQ)
coupled two-dimensional liquid chromatography followed electrospray ionization
tandem mass spectrometry (2D LC-MS/MS) proteomics technique. Among 391 identified
proteins with high confidence, 70 proteins were differentially expressed (fold
variation criteria, >1.2 or <0.83) between two groups (39 upregulated and 31
downregulated). Combining with Gene Ontology annotation, KEGG pathway analysis,
and literature retrieval, 5 proteins were chosen as key target biomarkers during
TJT therapeutic process. And the alteration profiles of these 5 proteins were
verified by ELISA and Western Blot. Proteins Kininogen 1 and Keratin 1 are
members of Kallikrein system, while Myeloperoxidase, Serum Amyloid protein A, and
Retinol binding protein 4 had been reported closely related to vascular
endothelial injury. Our study discovered 5 target biomarkers of the compound
Chinese medicine TJT. Secondly, this research initially revealed the
antihypertension therapeutic mechanism of this drug from a brand-new aspect.
PMID- 28408944
TI - PC2 Ovotransferrin: Characterization and Alternative Immunotherapeutic Activity.
AB - Characterization and evaluation of immunotherapeutic potential of ovotransferrin
PC2 (OTf PC2) were performed in this study. The ovoprotein was obtained from egg
white from hens immunized with bacterial antigens, pathogenic for humans. For the
negative control samples, OTf was extracted from eggs collected from Specific
Pathogen-Free (SPF) hens and purified by affinity chromatography on Protein G
agarose column with two eluting peaks: I, representing ovalbumin, and II,
ovotransferrin. The final apo-OTf form was reached by successive precipitation
with ammonium sulfate and citric acid and the holo-OTf form by saturating the apo
form with FeCl3. Multiple OTf PC2 samples were analyzed through Sodium Dodecyl
Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and, based on the molecular
marker migration model, the ovotransferrin (76.5 kDa) and ovalbumin (45 kDa) were
detected. The agglutination reaction exhibited statistically significant high
specificity of the multiple OTf PC2, by reacting with the antigens used for hens'
immunization. Following ELISA, it was established that OTf PC2 from hyperimmune
eggs has specificity for all antigens; the antibody titer was high, indicating
that OTf PC2 possesses immunological properties similar to immunoglobulin Y (Ig
Y). This study suggests that OTf PC2 immunological activity may play a crucial
role in the prevention and treatment of infections resistant to antibiotics and
OTf PC2 can also act as a valuable nutraceutical.
PMID- 28408943
TI - Effectiveness of Citrus Fruits on Helicobacter pylori.
AB - It is known that Helicobacter pylori infection is associated with chronic
gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects
of the treatment regimens and the development of antimicrobial resistance, a
number of natural compounds have been tested as potential alternatives. In this
review, we will examine the current knowledge on the effect of Citrus fruits and
their derivatives against H. pylori, highlighting the remaining outstanding
questions on the development of novel therapeutic strategies.
PMID- 28408945
TI - Recuperating Lung Decoction Attenuates the Oxidative Stress State of Chronic
Obstructive Pulmonary Disease by Inhibiting the MAPK/AP-1 Signal Pathway and
Regulating gamma-GCS.
AB - Purpose/Objective. To evaluate the effects of Recuperating Lung Decoction (RLD)
on the indices of oxidative stress in a rat model of COPD and detect the indices
of the MAPK/AP-1/gamma-GCS signal pathway for a further survey of the possible
targeting site of RLD. Methods/Materials. The rats of COPD were treated with RLD.
The protein levels of glutathione (GSH), oxidized glutathione (GSSG), 8-hydroxy-2
deoxyguanosine (8-OHdG), and 4-hydroxynonenal (4-HNE) were measured. In addition,
the levels of key signaling molecules (extracellular signal-regulated kinases
[ERK], the c-jun N-terminal kinase [JNKs signal pathway], and p38 MAP kinase
[p38MAPK], AP-1 proteins [C-fos, C-jun], and gamma-glutamyl-cysteine synthetase
[gamma-GCS-h]) of the MAPK/AP-1/gamma-GCS-h signal pathway were assessed.
Results. After treatment, the protein level of GSH and the ratio of GSH/GSSG were
increased and the amounts of 8-OHdG and 4-HNE were decreased significantly in
lung tissues when compared with the nontreated COPD group. Further results showed
that the RLD could effectively inhibit the MAPK pathway by inactivation of
p38MAPK and ERK and could also downregulate the AP-1 and the gamma-GCS-h genes
expressions in both protein and mRNA levels. Conclusion. RLD might improve the
state of oxidative stress by downregulation of the expression of gamma-GCS-h gene
by inhibition of the MAPK/AP-1 pathway, thereafter enhancing the ability of
antioxidation in COPD.
PMID- 28408946
TI - Computational and Mathematical Methods in Cardiovascular Diseases.
PMID- 28408947
TI - Diversification rates in Ctenodactylidae (Rodentia, Mammalia) from Mongolia.
AB - Gundis, or comb rats, are rodents of the family Ctenodactylidae. Extant gundis
are restricted to Africa and represent a vestige of the diversity that the
ctenodactylids attained at both palaeoecological and palaeobiogeographical
levels. Here, we present an updated review of the Ctenodactylidae from the Valley
of Lakes, Mongolia, based on the study of large collections now available. We
have recognised 13 valid species of ctenodactylids grouped into five genera:
Karakoromys, Huangomys, Tataromys, Yindirtemys, and Prodistylomys. The
ctenodactylids show an initial burst in diversification in the early Oligocene
followed by a sequential generic extinction of Karakoromys, Huangomys, and
Tataromys. A maximum richness peak at the late Oligocene was followed by a
profound diversity crisis. Yindirtemys, the only surviving genus, persisted into
the Miocene, joining three Prodistylomys species. These last representatives of
the group disappeared coinciding with the late Xiejian faunal reorganisation
(Mongolian biozone D).
PMID- 28408948
TI - Evolution of the genus Eucricetodon (Rodentia, Mammalia) from the Valley of Lakes
(Mongolia): a taxonomical description and update on the stratigraphical
distribution.
AB - The Oligocene fossil deposits from Valley of Lakes in Central Mongolia have
provided a wealth of rodent fossils. Among these, cricetids are a very important
part. To date, only the Miocene genera have been described in detail. Here, we
focus on the Oligocene genus Eucricetodon from this region. Eucricetodontinae are
the most abundant fossils in the Oligocene Valley of Lakes faunas. The present
study consists of the description of five species of cricetid rodents from 43
localities ranging in age from the early Oligocene to the early-late Oligocene.
In addition to Eucricetodon asiaticus described in Mongolia in 1923, we have
found Eucricetodon bagus and Eucricetodon jilantaiensis that were described from
Nei Mongol and Eucricetodon occidentalis discovered in Kazakhstan. This
taxonomical study provides new information regarding the evolution of the
Cricetidae in Central and Eastern Asia during the Oligocene and, more
particularly, regarding their phylogenetic relationships and the evolutionary
trends.
PMID- 28408949
TI - Foreword.
PMID- 28408950
TI - Dental prostheses mimic the natural enamel behavior under functional loading: A
review article.
AB - Alumina- and zirconia-based ceramic dental restorations are designed to repair
functionality as well as esthetics of the failed teeth. However, these materials
exhibited several performance deficiencies such as fracture, poor esthetic
properties of ceramic cores (particularly zirconia cores), and difficulty in
accomplishing a strong ceramic-resin-based cement bond. Therefore, improving the
mechanical properties of these ceramic materials is of great interest in a wide
range of disciplines. Consequently, spatial gradients in surface composition and
structure can improve the mechanical integrity of ceramic dental restorations.
Thus, this article reviews the current status of the functionally graded dental
prostheses inspired by the dentino-enamel junction (DEJ) structures and the
linear gradation in Young's modulus of the DEJ, as a new material design
approach, to improve the performance compared to traditional dental prostheses.
This is a remarkable example of nature's ability to engineer functionally graded
dental prostheses. The current article opens a new avenue for recent researches
aimed at the further development of new ceramic dental restorations for improving
their clinical durability.
PMID- 28408951
TI - Production and physiological role of NO in the oral cavity.
AB - Nitric oxide (NO) is a free radical which is produced from a wide variety of
cells and tissues in the human body. NO is involved in the regulation of many
physiological processes, such as vascular relaxation, neurotransmission, immune
regulation, and cell death. NO is generated by nitric oxide synthase (NOS), which
has three identified isoforms: neuronal type NOS (nNOS), endothelial type NOS
(eNOS), and inducible type NOS (iNOS). Different isoforms are expressed depending
on the organs, tissues, and cells, and investigation of the types and functions
of enzymes expressed in various tissues is underway. The oral cavity is a space
in which marked changes have been detected in NO levels, and each tissue is
constantly influenced by NO. NO is a component of saliva and is produced by oral
bacteria in the oral cavity and released by NOS expressed in oral mucosa. NOS
isoforms expressed under normal conditions differ among the oral organs. In
addition, the overexpression of NOS was involved in carcinogenesis and tumor
growth progression. This review summarized the expression of NOS and functions of
NO in oral cavity organs, and their roles in diseases and the influences of
treatments.
PMID- 28408952
TI - Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its
amino acid metabolism.
AB - Porphyromonas gingivalis, an asaccharolytic bacterium, utilizes amino acids as
energy and carbon sources. Since amino acids are incorporated into the bacterial
cells mainly as di- and tri-peptides, exopeptidases including dipeptidyl
peptidase (DPP) and tripeptidyl-peptidase are considered to be prerequisite
components for their metabolism. We recently discovered DPP11, DPP5, and
acylpeptidyl oligopeptidase in addition to previously reported DPP4, DPP7, and
prolyl tripeptidyl peptidase A. DPP11 is a novel enzyme specific for acidic P1
residues (Asp and Glu) and distributed ubiquitously in eubacteria, while DPP5 is
preferential for the hydrophobic P1 residue and the first entity identified in
prokaryotes. Recently, acylpeptidyl oligopeptidase with a preference for
hydrophobic P1 residues was found to release N-terminally blocked di- and tri
peptides. Furthermore, we also demonstrated that gingipains R and K contribute to
P1-basic dipeptide production. These observations implicate that most, if not
all, combinations of di- and tri-peptides are produced from extracellular
oligopeptides even with an N-terminal modification. Here, we review P. gingivalis
exopeptidases mainly in regard to their enzymatic characteristics. These
exopeptidases with various substrate specificities benefit P. gingivalis for
obtaining energy and carbon sources from the nutritionally limited subgingival
environment.
PMID- 28408953
TI - Editorial.
PMID- 28408954
TI - Rho GTPases in ameloblast differentiation.
AB - During tooth development, ameloblasts differentiate from inner enamel epithelial
cells to enamel-forming cells by modulating the signal pathways mediating
epithelial-mesenchymal interaction and a cell-autonomous gene network. The
differentiation process of epithelial cells is characterized by marked changes in
their morphology and polarity, accompanied by dynamic cytoskeletal reorganization
and changes in cell-cell and cell-matrix adhesion over time. Functional
ameloblasts are tall, columnar, polarized cells that synthesize and secrete
enamel-specific proteins. After deposition of the full thickness of enamel
matrix, ameloblasts become smaller and regulate enamel maturation. Recent
significant advances in the fields of molecular biology and genetics have
improved our understanding of the regulatory mechanism of the ameloblast cell
life cycle, mediated by the Rho family of small GTPases. They act as
intracellular molecular switch that transduce signals from extracellular stimuli
to the actin cytoskeleton and the nucleus. In our review, we summarize studies
that provide current evidence for Rho GTPases and their involvement in ameloblast
differentiation. In addition to the Rho GTPases themselves, their downstream
effectors and upstream regulators have also been implicated in ameloblast
differentiation.
PMID- 28408955
TI - Masticatory muscle tendon-aponeurosis hyperplasia: A new clinical entity of
limited mouth opening.
AB - Limited mouth opening is a common health problem that interferes with eating,
makes examination of the oral cavity difficult, and may increase the mortality
rate during emergency intubation. Here we introduce a disease designated as
masticatory muscle tendon-aponeurosis hyperplasia, which is a new clinical
condition of limited mouth opening. Most oral surgeons and dentists are still
unaware of this disease condition, thus increasing the risk of incorrect
diagnosis as some other disease, such as temporomandibular joint disorder. We
will review the clinical features, epidemiology, pathophysiology, etiology,
diagnosis, treatment, and prognosis of this disease and also appraise the
literature available on the subject.
PMID- 28408956
TI - A controversy with respect to occlusion.
AB - There are very little controversies on occlusion in healthy individuals, where
centric relation is regarded as the criterion for assessing the present occlusion
and also for establishing a new occlusal relationship between the upper and the
lower jaws. On the other hand, the occlusal position in patients with deformed
condyles still remains to be clarified. In this review, the effectiveness and
limits of centric relation in these patients are discussed. In addition, the
muscle induced occlusal positions, such as the muscular position and the terminal
positions of habitual closing movements, are suggested as a substitution for
centric relation. Finally, the importance of a stable intercuspal position, where
the habitual closing movements terminate without any premature tooth contact, is
emphasized.
PMID- 28408957
TI - Development of technique for in vitro embryotoxicity of dental biomaterials.
AB - The Embryonic Stem Cell Test (EST) developed in Germany in 1997 is known as a
screening test method capable of predicting the presence of unknown chemicals
influencing normal human development. Firstly, we investigated the embryotoxicity
of 24 types of monomer including dental monomers and dental alloy-component metal
elements using this test. Monomers including Bis-GMA contained in base resin of
composite resin exhibited weak embryotoxicity, and the toxicity level varied
among dental alloy-component metal elements. It was clarified that metal ions
eluted from currently sold dental alloys show no embryotoxicity. Then, we
investigated a method that also considers human metabolic activity, which is not
possible with the EST, in the results of embryotoxicity. In addition, an
evaluation method using a hybrid culture system for hepatocytes and mouse ES
cells and a method using oviduct or uterus cells for feeder cells were also
investigated.
PMID- 28408958
TI - Histology of human cementum: Its structure, function, and development.
AB - Cementum was first demonstrated by microscopy, about 180 years ago. Since then
the biology of cementum has been investigated by the most advanced techniques and
equipment at that time in various fields of dental sciences. A great deal of data
on cementum histology have been accumulated. These data have been obtained from
not only human, but also non-human animals, in particular, rodents such as the
mouse and rat. Although many dental histologists have reviewed histology of human
cementum, some descriptions are questionable, probably due to incorrect
comparison of human and rodent cementum. This review was designed to introduce
current histology of human cementum, i.e. its structure, function, and
development and to re-examine the most questionable and controversial conclusions
made in previous reports.
PMID- 28408959
TI - Role of the Wnt signaling molecules in the tooth.
AB - Wnt signaling plays a central role in many processes during embryonic development
and adult homeostasis. At least 19 types of Wnt ligands, receptors, transducers,
transcription factors, and antagonists have been identified in mammals. Two
distinct Wnt signaling pathways, the canonical signaling pathway and the
noncanonical signaling pathway, have been described. Some Wnt signaling pathway
components are expressed in the dental epithelium and mesenchyme during tooth
development in humans and mice. Functional studies and experimental analysis of
relevant animal models confirm the effects of Wnt signaling pathway on the
regulation of developing tooth formation and adult tooth homeostasis. Mutations
in some Wnt signaling pathway components have been identified in syndromic and
non-syndromic tooth agenesis. This review provides an overview of progress in
elucidating the role of Wnt signaling pathway components in the tooth and the
resulting possibilities for therapeutic development.
PMID- 28408960
TI - Molecular characterization and function of tenomodulin, a marker of tendons and
ligaments that integrate musculoskeletal components.
AB - Tendons and ligaments are dense fibrous bands of connective tissue that integrate
musculoskeletal components in vertebrates. Tendons connect skeletal muscles to
the bone and function as mechanical force transmitters, whereas ligaments bind
adjacent bones together to stabilize joints and restrict unwanted joint movement.
Fibroblasts residing in tendons and ligaments are called tenocytes and
ligamentocytes, respectively. Tenomodulin (Tnmd) is a type II transmembrane
glycoprotein that is expressed at high levels in tenocytes and ligamentocytes,
and is also present in periodontal ligament cells and tendon stem/progenitor
cells. Tnmd is related to chondromodulin-1 (Chm1), a cartilage-derived
angiogenesis inhibitor, and both Tnmd and Chm1 are expressed in the CD31-
avascular mesenchyme. The conserved C-terminal hydrophobic domain of these
proteins, which is characterized by the eight Cys residues to form four disulfide
bonds, may have an anti-angiogenic function. This review highlights the molecular
characterization and function of Tnmd, a specific marker of tendons and
ligaments.
PMID- 28408962
TI - The New Year has begun. Let's move forward!
PMID- 28408963
TI - Shedding quantitative fluorescence light on novel regulatory mechanisms in
skeletal biomedicine and biodentistry.
AB - Digitalized fluorescence images contain numerical information such as color
(wavelength), fluorescence intensity and spatial position. However, quantitative
analyses of acquired data and their validation remained to be established. Our
research group has applied quantitative fluorescence imaging on tissue sections
and uncovered novel findings in skeletal biomedicine and biodentistry. This
review paper includes a brief background of quantitative fluorescence imaging and
discusses practical applications by introducing our previous research. Finally,
the future perspectives of quantitative fluorescence imaging are discussed.
PMID- 28408964
TI - Magnetic resonance and sonographic imagings of masticatory muscle myalgia in
temporomandibular disorder patients.
AB - This article reviews recently published studies investigating the MRI and
sonographic diagnosis of masticatory muscle myalgia in temporomandibular disorder
patients. The MRI and sonographic features of muscle after treatment are also
discussed. Literature published within the last 15 years was obtained from the
PubMed database using the following Mesh terms: magnetic resonance imaging (MRI)
or sonography, masticatory muscle pain, and treatment. MRI and sonography enable
accurate visualization and evaluation of the masticatory muscles, thereby
increasing our understanding of pathology and cause of pain associated with these
muscles. Although therapeutic efficacy is often evaluated based on clinical
findings, MR and sonographic imaging studies may also be valuable.
PMID- 28408961
TI - The usefulness of diagnostic imaging for the assessment of pain symptoms in
temporomandibular disorders.
AB - The causes of pain symptoms in the temporomandibular joint (TMJ) and masticatory
muscle (MM) regions may not be determined by clinical examination alone. In this
review, we document that pain symptoms of the TMJ and MM regions in patients with
temporomandibular disorders (TMDs) are associated with computed tomography and
magnetic resonance (MR) findings of internal derangement, joint effusion,
osteoarthritis, and bone marrow edema. However, it is emphasized that these
imaging findings must not be regarded as the unique and dominant factors in
defining TMJ pain. High signal intensity and prominent enhancement of the
posterior disk attachment on fat saturation T2-weighted imaging and dynamic MR
imaging with contrast material are closely correlated with the severity of TMJ
pain. Magnetic transfer contrast, MR spectroscopy, diffusion tensor imaging, and
ultrasonography findings have helped identify intramuscular edema and contracture
as one of the causes of MM pain and fatigue. Recently, changes in brain as
detected by functional MR neuroimaging have been associated with changes in the
TMJ and MM regions. The thalamus, the primary somatosensory cortex, the insula,
and the anterior and mid-cinglate cortices are most frequently associated with
TMD pain.
PMID- 28408965
TI - Phospholipase C-related catalytically inactive protein can regulate obesity, a
state of peripheral inflammation.
AB - Obesity is defined as abnormal or excessive fat accumulation. Chronic
inflammation in fat influences the development of obesity-related diseases. Many
reports state that obesity increases the risk of morbidity in many diseases,
including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease,
stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased
mortality. Obesity is also associated with chronic neuropathologic conditions
such as depression and Alzheimer's disease. However, there is strong evidence
that weight loss reduces these risks, by limiting blood pressure and improving
levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)
cholesterol, and high-density lipoprotein (HDL)-cholesterol. Prevention and
control of obesity is complex, and requires a multifaceted approach. The
elucidation of molecular mechanisms driving fat metabolism (adipogenesis and
lipolysis) aims at developing clinical treatments to control obesity. We recently
reported a new regulatory mechanism in fat metabolism: a protein phosphatase
binding protein, phospholipase C-related catalytically inactive protein (PRIP),
regulates lipolysis in white adipocytes and heat production in brown adipocytes
via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation
and increased energy expenditure, resulting in a lean phenotype. Here, we
evaluate PRIP as a new therapeutic target for the control of obesity.
PMID- 28408966
TI - Gene Network Reconstruction using Global-Local Shrinkage Priors.
AB - Reconstructing a gene network from high-throughput molecular data is an important
but challenging task, as the number of parameters to estimate easily is much
larger than the sample size. A conventional remedy is to regularize or penalize
the model likelihood. In network models, this is often done locally in the
neighbourhood of each node or gene. However, estimation of the many
regularization parameters is often difficult and can result in large statistical
uncertainties. In this paper we propose to combine local regularization with
global shrinkage of the regularization parameters to borrow strength between
genes and improve inference. We employ a simple Bayesian model with non-sparse,
conjugate priors to facilitate the use of fast variational approximations to
posteriors. We discuss empirical Bayes estimation of hyper-parameters of the
priors, and propose a novel approach to rank-based posterior thresholding. Using
extensive model- and data-based simulations, we demonstrate that the proposed
inference strategy outperforms popular (sparse) methods, yields more stable
edges, and is more reproducible. The proposed method, termed ShrinkNet, is then
applied to Glioblastoma to investigate the interactions between genes associated
with patient survival.
PMID- 28408967
TI - The Temperature-Dependence of Multiphonon Relaxation of Rare-Earth Ions in Solid
State Hosts.
AB - Rare-earth ions are used in a wide range of emissive devices - ranging from
lasers to displays - where high optical efficiency and narrow-linewidth are
important. While their radiative properties are important, nonradiative
properties are also critical since they can reduce optical efficiency and
generate heat. In this paper, theories for multiphonon relaxation rate are
reviewed for rare-earth excited states in solid-state dielectric hosts. A range
of various approaches are used to simplify the mathematical form of the rate
equations. The 2H9/2 excited state of Er3+, responsible for a technologically
significant green emission, is modeled to show how the various theories manifest
an order-of-magnitude variation in the thermal dependence of the multiphonon
relaxation rate, as well as anomalous local minima in phonon scattering for
temperatures above 0 K. This work proposes a corrective term of two quanta
(Deltanu= + 2) of the mediating phonon energy to energy gap, so the calculated
and the experimentally determined relaxation rates are equal. Radiative quantum
efficiencies of both the 1G4->3H5 ~1.3 MUm and 3F3->3F2 ~7 MUm of Pr3+ are
calculated to show the importance of both proper measurement of phonon energy and
application of the multiphonon relaxation rate theory.
PMID- 28408968
TI - Effect of Ring Strain on the Charge Transport of a Robust Norbornadiene
Quadricyclane-Based Molecular Photoswitch.
AB - Integrating functional molecules into single-molecule devices is a key step
toward the realization of future computing machines based on the smallest
possible components. In this context, photoswitching molecules that can make a
transition between high and low conductivity in response to light are attractive
candidates. Here we present the synthesis and conductance properties of a new
type of robust molecular photothermal switch based on the norbornadiene (NB)
quadricyclane (QC) system. The transport through the molecule in the ON state is
dominated by a pathway through the pi-conjugated system, which is no longer
available when the system is switched to the OFF state. Interestingly, in the OFF
state we find that the same pathway contributes only 12% to the transport
properties. We attribute this observation to the strained tetrahedral geometry of
the QC. These results challenge the prevailing assumption that current will
simply flow through the shortest through-bond path in a molecule.
PMID- 28408969
TI - Effect of Red Orange Juice Consumption on Body Composition and Nutritional Status
in Overweight/Obese Female: A Pilot Study.
AB - The main objective of this research was to determine whether a commercial orange
juice rich in anthocyanins could have an effect on body weight and on clinical
parameters related to obesity including antioxidant status, lipid profile, and
metabolic and inflammatory biomarkers. 11 women with an average BMI of 34.4 +/-
4.8 kg/m2 were enrolled in a pilot study. Over a period of 12 weeks they received
500 mL daily dose into two doses (250 mL) of commercial red orange juice (COJ).
The biochemical parameters were measured at baseline and at the end of the study
(12 weeks). One month later upon free diet, a follow-up was performed measuring
the same variables. The daily consumption of 500 mL of COJ had no significant
effects on body weight, while there was a decrease in total cholesterol and LDL
cholesterol. The grade of obesity implies different changes in inflammation
biomarkers. In obese women, our data do not seem to support evidence that
commercial red orange juice consumption acts as functional food preventing
obesity and metabolic disorders such as insulin resistance and/or inflammatory
status.
PMID- 28408970
TI - Differential Regulation of Cardiac Function and Intracardiac Cytokines by
Rapamycin in Healthy and Diabetic Rats.
AB - Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin
improves cardiac functions and extends lifespan by inhibiting the mechanistic
target of rapamycin complex 1 (mTORC1). However, in diabetic murine models,
Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an
immunosuppressant, we examined whether Rapamycin (750 MUg/kg/day) modulates
intracardiac cytokines, which affect the cardiac immune response, and cardiac
function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin
suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but
increased glucose. Although Rapamycin improved multiple diastolic parameters
(E/E', E'/A', E/Vp) initially, these improvements were reversed or absent in ZO
at the end of treatment, despite suppression of cardiac fibrosis and
phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity(r)
Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in
response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis
in ZL without increasing phosphoSer473Akt and differentially modulated anti
fibrotic IL-10, IFNgamma, and GM-CSF in ZL and ZO. Therefore, fundamental
difference in intracardiac host defense between diabetic ZO and healthy ZL,
combined with differential regulation of intracardiac cytokines by Rapamycin in
ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment
in health and diabetes.
PMID- 28408972
TI - A data-driven approach to estimating the number of clusters in hierarchical
clustering.
AB - DNA microarray and gene expression problems often require a researcher to perform
clustering on their data in a bid to better understand its structure. In cases
where the number of clusters is not known, one can resort to hierarchical
clustering methods. However, there currently exist very few automated algorithms
for determining the true number of clusters in the data. We propose two new
methods (mode and maximum difference) for estimating the number of clusters in a
hierarchical clustering framework to create a fully automated process with no
human intervention. These methods are compared to the established elbow and gap
statistic algorithms using simulated datasets and the Biobase Gene ExpressionSet.
We also explore a data mixing procedure inspired by cross validation techniques.
We find that the overall performance of the maximum difference method is
comparable or greater to that of the gap statistic in multi-cluster scenarios,
and achieves that performance at a fraction of the computational cost. This
method also responds well to our mixing procedure, which opens the door to future
research. We conclude that both the mode and maximum difference methods warrant
further study related to their mixing and cross-validation potential. We
particularly recommend the use of the maximum difference method in multi-cluster
scenarios given its accuracy and execution times, and present it as an
alternative to existing algorithms.
PMID- 28408971
TI - Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain:
Involvement of NADPH Oxidase.
AB - Maternal deprivation (MD) causes perinatal stress, with subsequent behavioral
changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of
the major generators of reactive oxygen species, known to play a role in stress
response in different tissues. The aim of this study was to elucidate the long
term effects of MD on the expression of NADPH oxidase subunits (gp91phox,
p22phox, p67phox, p47phox, and p40phox). Activities of cytochrome C oxidase and
respiratory chain Complex I, as well as the oxidative stress parameters using
appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats
were exposed to a 24 h maternal deprivation and sacrificed at young adult age.
The structures affected by perinatal stress, cortex, hippocampus, thalamus, and
caudate nuclei were investigated. The most prominent findings were increased
expressions of gp91phox in the cortex and hippocampus, increased expression of
p22phox and p40phox, and decreased expression of gp91phox, p22phox, and p47phox
in the caudate nuclei. Complex I activity was increased in all structures except
cortex. Content of reduced glutathione was decreased in all sections while region
specific changes of other oxidative stress parameters were found. Our results
indicate the presence of long-term redox alterations in MD rats.
PMID- 28408973
TI - A multi-scale computational model of the effects of TMS on motor cortex.
AB - The detailed biophysical mechanisms through which transcranial magnetic
stimulation (TMS) activates cortical circuits are still not fully understood.
Here we present a multi-scale computational model to describe and explain the
activation of different cell types in motor cortex due to transcranial magnetic
stimulation. Our model determines precise electric fields based on an individual
head model derived from magnetic resonance imaging and calculates how these
electric fields activate morphologically detailed models of different neuron
types. We predict detailed neural activation patterns for different coil
orientations consistent with experimental findings. Beyond this, our model allows
us to predict activation thresholds for individual neurons and precise initiation
sites of individual action potentials on the neurons' complex morphologies.
Specifically, our model predicts that cortical layer 3 pyramidal neurons are
generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining
the lower stimulation thresholds observed for I-waves compared to D-waves. It
also predicts differences in the regions of activated cortical layer 5 and layer
3 pyramidal cells depending on coil orientation. Finally, it predicts that under
standard stimulation conditions, action potentials are mostly generated at the
axon initial segment of corctial pyramidal cells, with a much less important
activation site being the part of a layer 5 pyramidal cell axon where it crosses
the boundary between grey matter and white matter. In conclusion, our
computational model offers a detailed account of the mechanisms through which TMS
activates different cortical cell types, paving the way for more targeted
application of TMS based on individual brain morphology in clinical and basic
research settings.
PMID- 28408974
TI - Bringing a genomic perspective to the safety of drug treatment in oncology.
AB - This article describes the clinical relevance of toxicity of therapies
administered to patients with cancer, putting the patient, rather than disease,
at the center of the evaluation of safety of anti-cancer therapy. Hence, the
implications of adverse events are described from the patient perspective,
focusing on the impact of patient safety on quality of life and efficacy of
treatment. Issues revolving around other types of safety, such as financial
toxicity, are also discussed. The role played by genetics in the assessment of a
patient's risk of adverse events is also discussed, both in relation to the
potential of genomic research and in the context of current tools of fruition in
clinical care.
PMID- 28408975
TI - X chromosome inactivation: new players in the initiation of gene silencing.
AB - X chromosome inactivation (XCI) is a dosage compensation process that was adopted
by female mammals to balance gene dosage between XX females and XY males. XCI
starts with the upregulation of the non-coding RNA Xist, after which most X
linked genes are silenced and acquire a repressive chromatin state. Even though
the chromatin marks of the inactive X have been fairly well described, the
mechanisms responsible for the initiation of XCI remain largely unknown. In this
review, we discuss recent developments that revealed unexpected factors playing a
role in XCI and that might be of crucial importance to understand the mechanisms
responsible for the very first steps of this chromosome-wide gene-silencing
event.
PMID- 28408976
TI - When TADs go bad: chromatin structure and nuclear organisation in human disease.
AB - Chromatin in the interphase nucleus is organised as a hierarchical series of
structural domains, including self-interacting domains called topologically
associating domains (TADs). This arrangement is thought to bring enhancers into
closer physical proximity with their target genes, which often are located
hundreds of kilobases away in linear genomic distance. TADs are demarcated by
boundary regions bound by architectural proteins, such as CTCF and cohesin,
although much remains to be discovered about the structure and function of these
domains. Recent studies of TAD boundaries disrupted in engineered mouse models
show that boundary mutations can recapitulate human developmental disorders as a
result of aberrant promoter-enhancer interactions in the affected TADs. Similar
boundary disruptions in certain cancers can result in oncogene overexpression,
and CTCF binding sites at boundaries appear to be hyper-mutated across cancers.
Further insights into chromatin organisation, in parallel with accumulating whole
genome sequence data for disease cohorts, are likely to yield additional valuable
insights into the roles of noncoding sequence variation in human disease.
PMID- 28408977
TI - Mitogenomes of Giant-Skipper Butterflies reveal an ancient split between deep and
shallow root feeders.
AB - Background: Giant-Skipper butterflies from the genus Megathymus are North
American endemics. These large and thick-bodied Skippers resemble moths and are
unique in their life cycles. Grub-like at the later stages of development,
caterpillars of these species feed and live inside yucca roots. Adults do not
feed and are mostly local, not straying far from the patches of yucca plants.
Methods: Pieces of muscle were dissected from the thorax of specimens and genomic
DNA was extracted (also from the abdomen of a specimen collected nearly 60 years
ago). Paired-end libraries were prepared and sequenced for 150bp from both ends.
The mitogenomes were assembled from the reads followed by a manual gap-closing
procedure and a phylogenetic tree was constructed using a maximum likelihood
method from an alignment of the mitogenomes. Results: We determined mitogenome
sequences of nominal subspecies of all five known species of Megathymus and
Agathymus mariae to confidently root the phylogenetic tree. Pairwise sequence
identity indicates the high similarity, ranging from 88-96% among coding regions
for 13 proteins, 22 tRNAs and 2 rRNA, with a gene order typical for mitogenomes
of Lepidoptera. Phylogenetic analysis confirms that Giant-Skippers (Megathymini)
originate within the subfamily Hesperiinae and do not warrant a subfamily rank.
Genus Megathymus is monophyletic and splits into two species groups. M. streckeri
and M. cofaqui caterpillars feed deep in the main root system of yucca plants and
deposit frass underground. M. ursus, M. beulahae and M. yuccae feed in the yucca
caudex and roots near the ground, and deposit frass outside through a "tent" (a
silk tube projecting from the center of yucca plant). M. yuccae and M. beulahae
are sister species consistently with morphological similarities between them.
Conclusions: We constructed the first DNA-based phylogeny of the genus Megathymus
from their mitogenomes. The phylogeny agrees with morphological considerations.
PMID- 28408978
TI - Associative memory cells: Formation, function and perspective.
AB - Associative learning and memory are common activities in life, and their cellular
infrastructures constitute the basis of cognitive processes. Although neuronal
plasticity emerges after memory formation, basic units and their working
principles for the storage and retrieval of associated signals remain to be
revealed. Current reports indicate that associative memory cells, through their
mutual synapse innervations among the co-activated sensory cortices, are
recruited to fulfill the integration, storage and retrieval of multiple
associated signals, and serve associative thinking and logical reasoning. In this
review, we aim to summarize associative memory cells in their formation, features
and functional impacts.
PMID- 28408979
TI - Studying human immunodeficiencies in humans: advances in fundamental concepts and
therapeutic interventions.
AB - Immunodeficiencies reveal the crucial role of the immune system in defending the
body against microbial pathogens. Given advances in genomics and other
technologies, this is currently best studied in humans who have inherited
monogenic diseases. Such investigations have provided insights into how gene
products normally function in the natural environment and have opened the door to
new, exciting treatments for these diseases.
PMID- 28408980
TI - Wars between microbes on roots and fruits.
AB - Microbes in nature often live in unfavorable conditions. To survive, they have to
occupy niches close to food sources and efficiently utilize nutrients that are
often present in very low concentrations. Moreover, they have to possess an
arsenal of attack and defense mechanisms against competing bacteria. In this
review, we will discuss strategies used by microbes to compete with each other in
the rhizosphere and on fruits, with a focus on mechanisms of inter- and intra
species antagonism. Special attention will be paid to the recently discovered
roles of volatile organic compounds. Several microbes with proven capabilities in
the art of warfare are being applied in products used for the biological control
of plant diseases, including post-harvest control of fruits and vegetables.
PMID- 28408981
TI - RNA and Proteins: Mutual Respect.
AB - Proteins and RNA are often found in ribonucleoprotein particles (RNPs), where
they function in cellular processes to synthesize proteins (the ribosome),
chemically modify RNAs (small nucleolar RNPs), splice pre-mRNAs (the
spliceosome), and, on a larger scale, sequester RNAs, degrade them, or process
them (P bodies, Cajal bodies, and nucleoli). Each RNA-protein interaction is a
story in itself, as both molecules can change conformation, compete for binding
sites, and regulate cellular functions. Recent studies of Xist long non-coding
RNP, the U4/5/6 tri-small nuclear RNP complex, and an activated state of a
spliceosome reveal new features of RNA interactions with proteins, and, although
their stories are incomplete, they are already fascinating.
PMID- 28408982
TI - What causes amyotrophic lateral sclerosis?
AB - Amyotrophic lateral sclerosis is a neurodegenerative disease predominantly
affecting upper and lower motor neurons, resulting in progressive paralysis and
death from respiratory failure within 2 to 3 years. The peak age of onset is 55
to 70 years, with a male predominance. The causes of amyotrophic lateral
sclerosis are only partly known, but they include some environmental risk factors
as well as several genes that have been identified as harbouring disease
associated variation. Here we review the nature, epidemiology, genetic
associations, and environmental exposures associated with amyotrophic lateral
sclerosis.
PMID- 28408983
TI - Recent advances in understanding Epstein-Barr virus.
AB - Epstein-Barr virus (EBV) is a common human herpes virus known to infect the
majority of the world population. Infection with EBV is often asymptomatic but
can manifest in a range of pathologies from infectious mononucleosis to severe
cancers of epithelial and lymphocytic origin. Indeed, in the past decade, EBV has
been linked to nearly 10% of all gastric cancers. Furthermore, recent advances in
high-throughput next-generation sequencing and the development of humanized mice,
which effectively model EBV pathogenesis, have led to a wealth of knowledge
pertaining to strain variation and host-pathogen interaction. This review
highlights some recent advances in our understanding of EBV biology, focusing on
new findings on the early events of infection, the role EBV plays in gastric
cancer, new strain variation, and humanized mouse models of EBV infection.
PMID- 28408984
TI - B-cell tolerance and autoimmunity.
AB - Self-reactive B cells are tolerized at various stages of B-cell development and
differentiation, including the immature B-cell stage (central tolerance) and the
germinal center (GC) B-cell stage, and B-cell tolerance involves various
mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells
generated by random immunoglobulin variable gene rearrangements are tolerized by
central tolerance and anergy in the periphery, and these processes involve
apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and
regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP
1. Self-reactive B cells generated by somatic mutations during GC reaction are
also eliminated. Fas is not directly involved in this process but prevents
persistence of GC reaction that allows generation of less stringently regulated B
cells, including self-reactive B cells. Defects in self-tolerance preferentially
cause lupus-like disease with production of anti-nuclear antibodies, probably due
to the presence of a large potential B-cell repertoire reactive to nucleic acids
and the presence of nucleic acid-induced activation mechanisms in various immune
cells, including B cells and dendritic cells. A feed-forward loop composed of
anti-nuclear antibodies produced by B cells and type 1 interferons secreted from
nucleic acid-activated dendritic cells plays a crucial role in the development of
systemic lupus erythematosus.
PMID- 28408985
TI - New drugs in psychiatry: focus on new pharmacological targets.
AB - The approval of psychotropic drugs with novel mechanisms of action has been rare
in recent years. To address this issue, further analysis of the pathophysiology
of neuropsychiatric disorders is essential for identifying new pharmacological
targets for psychotropic medications. In this report, we detail drug candidates
being examined as treatments for psychiatric disorders. Particular emphasis is
placed on agents with novel mechanisms of action that are being tested as
therapies for depression, schizophrenia, or Alzheimer's disease. All of the
compounds considered were recently approved for human use or are in advanced
clinical trials. Drugs included here are new antipsychotic medications endowed
with a preferential affinity at dopamine D3 receptor (cariprazine) or at
glutamatergic or cannabinoid receptors, as well as vortioxetine, a drug approved
for managing the cognitive deficits associated with major depression. New
mechanistic approaches for the treatment of depression include intravenous
ketamine or esketamine or intranasal esketamine. As for Alzheimer's disease, the
possible value of passive immunotherapy with agents such as aducanumab is
considered to be a potential disease-modifying approach that could slow or halt
the progressive decline associated with this devastating disorder.
PMID- 28408986
TI - Pain management using acetaminophen throughout postoperative course of
laparoscopic colorectal surgery: A case-matched control study.
AB - BACKGROUD: The main advantage of laparoscopic surgery is that it is minimally
invasive because of the use of small incisions. An approach using small incisions
offers many benefits including attenuation of surgical wound pain. However, the
presence of postoperative pain may undermine the advantages of laparoscopic
surgery as a minimally invasive technique. In addition, perioperative pain
management is an important factor affecting recovery after surgery. This study
investigated the usefulness of a multimodal approach to postoperative pain
management with acetaminophen as a baseline analgesic after minimally invasive
laparoscopic colorectal surgery. MATERIALS AND METHODS: The study included 40
patients who underwent laparoscopic colorectal surgery for colorectal cancer. 20
patients received acetaminophen as a baseline analgesic for postoperative pain
management and 20 received epidural anesthesia. RESULTS: The urethral catheter
could be removed earlier in the acetaminophen group (2.1 +/- 0.22 days
postoperatively) compared with the epidural group (4.1 +/- 0.45days
postoperatively). The frequencies of vertigo were significantly lower in the
acetaminophen than epidural group (10.0% and 45.0%, respectively). The
frequencies of the use of analgesics on an as-needed basis for postoperative pain
relief as well as the variabilities in these frequencies, although not
significantly different between the acetaminophen and epidural groups, were lower
in the acetaminophen group than the epidural group. CONCLUSION: We herein
demonstrated that postoperative pain management with acetaminophen as a baseline
analgesic, and without the use of epidural anesthesia, is a safe and useful
analgesic modality.
PMID- 28408987
TI - Saving from unnecessary pancreaticoduodenectomy. Brunner's gland hamartoma: Case
report on a rare duodenal lesion and exhaustive literature review.
AB - INTRODUCTION: Brunner's gland hamartoma (BGH) is an infrequently encountered,
benign, polypoid proliferation of Brunner's glands. Usually these lesions are
asymptomatic, just only occasionally presenting with duodenal obstruction or
bleeding signs and mimicking a tumoral lesion. CASE PRESENTATION: A 72-year-old
male, referred for recurrent vomiting and epigastralgia, was investigated and all
preoperative findings were suggestive of a tumour of the duodenum. During the
scheduled pancreaticoduodenectomy a mass, resultant to a polyp, was palpatory
felt inside the duodenum and then successfully and completely resected through a
duodenotomy avoiding surgical overtreatment and connected postoperative
morbidities. Histological analysis showed hyperplasia of Brunner's glands
correspondent to a Brunner's gland hamartoma. BGH was undiagnosed before surgery,
due to its particular sub-mucosal growth simulating an expanding process starting
from the duodenum, and secondly due to unsuccessful biopsies performed during
endoscopic procedure. CONCLUSION: BGH is a rare lesion featuring, when
symptomatic, obstructive or bleeding symptoms. Surgical treatment represents the
gold standard approach in case of lesions that are technically impossible to
remove endoscopically or in case of an undiagnosed lesion. Herein, we report a
case of a patient presenting with a duodenal lesion mimicking, in all
preoperative findings, a tumour of the duodenum. Duodenotomy and resection of the
BGH provided a definitive cure avoiding surgical overtreatment. An intraoperative
deep analysis of all surgical cases still remain crucial for a right therapeutic
choice even in a new era for surgical technology. For similar intraoperative
findings we recommend this technique.
PMID- 28408988
TI - Sutureless functional end-to-end anastomosis using a linear stapler with
polyglycolic acid felt for intestinal anastomoses.
AB - BACKGROUND: Gastrointestinal anastomosis remains associated with a considerable
burden of morbidity and, in some cases, mortality. Functional end-to-end
anastomosis, whilst extremely efficient, is vulnerable to increased intestinal
pressure in the immediate postoperative period, which may predispose to
development of anastomotic leakage or bleeding. Therefore, there is a requirement
for new techniques that facilitate safe and efficacious anastomotic procedures.
MATERIALS AND METHODS: This study examined the clinical application of functional
end-to-end anastomosis with a stapler that automatically applies a bioabsorbable
polyglycolic acid sheet (Endo GIATM Reinforced Reload with Tri-StapleTM
Technology). A porcine model was used to examine functional end-to-end
anastomosis with and without application of a bioabsorbable polyglycolic acid
sheet. As the crotch of the anastomosis is considered the weakest point, a probe
was used to test the integrity of these anastomoses. Furthermore, we performed
functional end-to-end anastomosis using the Endo GIATM Reinforced stapler in a
clinical series of 20 patients undergoing gastrointestinal tract resection. In
all cases, functional end-to-end anastomosis was performed without suture
reinforcement. RESULTS: Small intestine anastomoses in the animal study exhibited
no weakness at the crotch of the anastomosis, as tested with a probe, suggesting
an increased resiliency to conventional complications of functional end-to-end
anastomosis. In the clinical population, no postoperative complications were
noted. No adhesive intestinal obstruction was noted. CONCLUSION: Sutureless
functional end-to-end anastomosis using the Endo GIATM Reinforced appears to be
safe, efficacious, and straightforward. Reinforcement of the crotch site with a
bioabsorbable polyglycolic acid sheet appears to mitigate conventional problems
with crotch-site vulnerability.
PMID- 28408989
TI - Timing of oral refeeding in acute pancreatitis: A systematic review and meta
analysis.
AB - BACKGROUND AND AIM: The optimal timing of oral refeeding in acute pancreatitis is
unclear. This study aimed to perform a systematic review with meta-analysis of
randomized controlled trials (RCTs) that compared early oral refeeding with
standard oral refeeding in acute pancreatitis. METHODS: PubMed, the Cochrane
library, and the Igaku-Chuo-Zasshi database were searched in order to identify
RCTs eligible for inclusion in the systematic review. The weighted mean
differences (WMDs) or odds ratios (ORs) with 95% confidence intervals (CIs) were
calculated. RESULTS: Five eligible RCTs were included. Compared with standard
oral refeeding, early oral refeeding significantly decreased the length of
hospital stay (WMD: -2.22, 95%CI: -3.37 to -1.08, p = 0.0001). Although there was
heterogeneity (I2 = 56%, p = 0.06), subgroup analysis of the refeeding criteria
(immediate group and hungry group) eliminated the heterogeneity. There was no
significant difference between the early refeeding group and standard refeeding
groups with respect abdominal pain and distension (OR 1.14; 95%CI 0.65-1.99 and
OR 1.53; 95%CI 0.81-2.90). CONCLUSIONS: Compared with standard oral refeeding,
early oral refeeding safely reduced the length of hospital stay in patients with
acute pancreatitis.
PMID- 28408990
TI - Endoscopic modalities for the diagnosis of Barrett's oesophagus.
AB - Barrett's oesophagus is a pre-malignant condition associated with the development
of oesophageal adenocarcinoma. Currently white light endoscopy and biopsy is the
mainstay diagnostic tool. Yet this approach is troubled by issues related to
cumbersome biopsy sampling, biopsy sampling errors and cost. Therefore in order
to overcome such adversity, there needs to be evolutionary advancement in terms
of diagnosis, which should address these concerns and ideally enhance risk
stratification in order to provide timely management in real time. This review
highlights the current endoscopic tools aimed to enhance the diagnosis of
Barrett's oesophagus and its subsequent progression.
PMID- 28408991
TI - Transplantation of tissue-engineered cell sheets for stricture prevention after
endoscopic submucosal dissection of the oesophagus.
AB - BACKGROUND AND OBJECTIVE: Endoscopic mucosal dissection (ESD) is a treatment
option for oesophagus tumours localized to the mucosa enabling en bloc removal of
large lesions. The resulting larger mucosal defects have resulted in an increase
in the occurrence of post-treatment strictures. Transplantation of autologous
cell sheets, cultured from oral mucosa, has been shown to prevent post-ESD
strictures. The aim of the study was to assess the efficacy and safety of cell
sheet transplantation after oesophageal ESD in a Western patient population where
reflux-associated pre-malignant and malignant conditions predominate. METHODS:
Patients with Barrett's oesophagus associated high-grade dysplasia or early
adenocarcinoma where ESD entailed a resection >3 cm in length and >=75% of the
circumference were eligible for treatment under hospital exemption. Cell sheets
were cultured from buccal mucosa according to Good Manufacturing Practice and
were endoscopically applied to the post-ESD defect directly after resection.
Patients were followed with weekly endoscopy examinations, including confocal
laser microscopy, for a total of four weeks. RESULTS: Five patients were treated.
ESD was extensive with resections being circumferential in three patients and 9
10 cm in length in two. The number of transplanted cell sheets ranged from two to
six. Three patients developed strictures requiring two to five dilatation
sessions. CONCLUSIONS: Cell sheet transplantation shows to be safe and feasible
in a Western population. Results suggest that transplantation has a protective
effect on the mucosal defect after ESD, decreasing both the risk for and extent
of stricture formation.
PMID- 28408992
TI - The risk of oesophageal adenocarcinoma in a prospectively recruited Barrett's
oesophagus cohort.
AB - BACKGROUND: Varying rates of oesophageal adenocarcinoma (OAC) complicating
Barrett's oesophagus (BO) have been reported. Recent studies and meta-analyses
suggest a lower incidence, questioning the value of endoscopic surveillance. AIM:
We aimed to retrospectively examine the rate of OAC, risk factors and causes of
death in a prospectively recruited BO cohort. METHODS: Data from patients with BO
from a cohort from 1982-2007 were studied. Patients were subdivided into
surveyed, failed to attend surveillance and unfit for surveillance. Standardised
mortality ratios (SMR) were calculated for common causes of death. Cox
proportional hazards models were used to determine which factors were associated
with progression to OAC. RESULTS: In total, 671 BO patients (61% male) were
studied; 37 (76% male) were diagnosed with OAC. OAC incidence was 0.47% per annum
and stable across three decades (1982-1991 0.56%, 1992-2001 0.46%, 2002-2012
0.41% (p = 0.8)). All-cause mortality was increased for the whole cohort (SMR
163(95% CI 145-183)). Mortality from OAC appeared higher in patients who failed
to attend surveillance (SMR 3216(95% CI 1543-5916)) compared with surveyed (SMR
1753(95% CI 933-2998)) and those unfit for surveillance due to co-morbidity (SMR
440(95% CI 143-1025)). Multivariable analysis identified low-grade dysplasia (HR
4.4(95% CI 1.56-12.43), p = 0.005) and length of BO (HR 1.2(95% (1.1-1.3)), p <
0.001)) as associated with OAC. CONCLUSIONS: Progression to OAC appeared stable
over three decades at 0.47% per annum. Patients with BO had a modest increase in
all-cause mortality and a large increase in OAC mortality, particularly if fit
for surveillance. Low-grade dysplasia and the length of the BO segment were
associated with developing OAC.
PMID- 28408993
TI - Real-world Helicobacter pylori diagnosis in patients referred for
esophagoduodenoscopy: The gap between guidelines and clinical practice.
AB - BACKGROUND AND AIMS: Histopathology is the most accurate test to detect H. pylori
when performed correctly with unknown validity in daily practice clinic settings.
We aimed to determine the rate of potentially false-negative H. pylori results
that might be due to continued use of proton pump inhibitors (PPIs) in routine
endoscopy practice. We also aimed to establish whether gastroenterologists
recommend routine cessation of PPIs before esophagogastroduodenoscopy (EGD) and
whether they regularly document that biopsies for H. pylori testing have been
taken while the patients are on PPI treatment. METHODS: Detailed information
about three known factors (PPIs, antibiotics and prior H. pylori eradication
treatment), which may cause histology or rapid urease test (RUT) to be
unreliable, had been prospectively collected through interviews using a
questionnaire before each test. Gastric biopsies were stained with H&E for
histological analysis. RESULTS: A total of 409 individuals at three academic
gastroenterology institutions were tested 200 times with histology. Fifty-six per
cent (68 of 122) of all negative tests fell in the category of continuing PPI
use, which had the potential to make the histology and RUT results unreliable.
CONCLUSIONS: These data demonstrate a clear and important gap between current
guidelines and real-world practice with regards to the diagnosis of H. pylori
during EGD. A negative histology or RUT should be considered false negative until
potential protocol violations are excluded. Documentation of PPI use during the
EGD should be an integral part of the EGD report. The current practice of taking
biopsies for H. pylori testing in patients under PPIs should be reevaluated.
PMID- 28408994
TI - Endoscopic management of patients with post-surgical leaks involving the
gastrointestinal tract: A large case series.
AB - BACKGROUND: Post-surgical anastomotic leaks often require a re-intervention, are
associated with a definite morbidity and mortality, and with relevant costs. We
described a large series of patients with different post-surgical leaks involving
the gastrointestinal tract managed with endoscopy as initial approach. METHODS:
This was a retrospective analysis of prospectively collected cases with
anastomotic leaks managed with different endoscopic approaches (with surgical or
radiological drainage when needed) in two endoscopic centres during 5 years.
Interventions included: (1) over-the-scope clip (OTSC) positioning; (2) placement
of a covered self-expanding metal stent (SEMS); (3) fibrin glue injection
(Tissucol); and (4) endo-sponge application, according to both the endoscopic
feature and patient's status. RESULTS: A total of 76 patients underwent
endoscopic treatment for a leak either in the upper (47 cases) or lower (29
cases) gastrointestinal tract, and the approach was successful in 39 (83%) and 22
(75.9%) patients, respectively, accounting for an overall 80.3% success rate.
Leak closure was achieved in 84.9% and 78.3% of patients managed by using a
single or a combination of endoscopic devices. Overall, leak closure failed in 15
(19.7%) patients, and the surgical approach was successful in all 14 patients who
underwent re-intervention, whilst one patient died due to sepsis at 7 days.
CONCLUSIONS: Our data suggest that an endoscopic approach, with surgical or
radiological drainage when needed, is successful and safe in the majority of
patients with anastomotic gastrointestinal leaks. Therefore, an endoscopic
treatment could be attempted before resorting to more invasive, costly and risky
re-intervention.
PMID- 28408995
TI - Multiple, zonal and multi-zone adenoma detection rates according to quality of
cleansing during colonoscopy.
AB - BACKGROUND: The safety and diagnostic accuracy of colonoscopy depend on the
quality of colon cleansing. The adenoma detection rate is usually used as a
quality measurement score. OBJECTIVE: We aimed to introduce and evaluate three
new parameters to determine polyps and adenomas segmental localization and their
distribution in association with different bowel preparation levels during
colonoscopy. We introduce the multiple adenoma detection rate (the percentage of
patients with >2 adenomas diagnosed during colonoscopy), the zonal adenoma
detection rate (the percentage of patients with >2 adenomas diagnosed during
colonoscopy in different colon areas (rectum, sigmoid, descending, transverse,
ascending and cecum colon)), and multi-zone adenoma detection rate (the
percentage of patients with >2 adenomas diagnosed during colonoscopy in different
colon areas with at least a segment between them with or without lesions (i.e.
rectum and descending colon with or without lesions in the sigmoid)). METHODS: We
prospectively enrolled outpatients who underwent colonoscopy from January 2013 to
October 2014. The bowel preparation quality, according to the Aronchick modified
scale, number and location of lesions, Paris classification and histology, were
recorded. The multiple adenoma/polyp detection rate, zonal adenoma/polyp
detection rate, and multi-zone adenoma/polyp detection rate were determined.
RESULTS: In total, 519 consecutive patients (266/253 M/F; mean age 55.3 +/- 12.8
years) were enrolled. The adenoma and polyp detection rates were 21% and 35%,
respectively. Multiple adenomas were detected in 28 patients. Adenoma and polyp
detection rate and new parameters were statistically significantly higher in the
optimal as compared with the adequate bowel preparation. CONCLUSIONS: An optimal
level of bowel preparation was strongly associated not only with a higher adenoma
detection rate, but also with a higher chance of detecting multiple clinically
relevant lesions in adjacent or discrete segments of the colon.
PMID- 28408996
TI - Risk factors for complications after ileocolonic resection for Crohn's disease
with a major focus on the impact of preoperative immunosuppressive and biologic
therapy: A retrospective international multicentre study.
AB - BACKGROUND: Author note: TY, AS, YS, FVT and PGK designed the study. All authors
did data collection and gave scientific contribution to the study design and
discussion. TY, AS and PGK drafted the article. All authors read and approved the
final version of the manuscript.In the era of biologic agents, risk factors for
complications following resection for Crohn's disease have not been fully
identified. In particular, the association of preoperative use of
immunosuppressive and biologic agents with the incidence of complications after
resection remains to be elucidated. AIM: This retrospective multicentre study
aimed to identify risk factors for complications after ileocolonic resection for
Crohn's disease, with a major focus on the impact of preoperative
immunosuppressive and biologic therapy. METHODS: A total of 231 consecutive
patients who underwent ileocolonic resections for active Crohn's disease in seven
inflammatory bowel disease referral centres from three countries (Japan, Brazil
and Italy) were included. The following variables were investigated as potential
risk factors: age at surgery, gender, behaviour of Crohn's disease (perforating
vs. non-perforating disease), smoking, preoperative use (within eight weeks
before surgery) of steroids, immunosuppressants and biologic agents, previous
resection, blood transfusion, surgical procedure (open vs. laparoscopic
approach), and type of anastomosis (side-to-side vs. end-to-end). Postoperative
complications occurring within 30 days after surgery were recorded. RESULTS: The
rates of overall complications, intra-abdominal sepsis, and anastomotic leak were
24%, 12% and 8%, respectively. Neither immunosuppressive nor biologic therapy
prior to surgery was significantly associated with the incidence of overall
complications, intra-abdominal sepsis or anastomotic leak. In multivariate
analysis, blood transfusion, perforating disease and previous resection were
significant risk factors for overall complications (odds ratio [OR] 3.02, 95%
confidence interval [CI] 1.21-7.52; P = 0.02), intra-abdominal sepsis (OR 2.67,
95% CI 1.04-6.86; P = 0.04) and anastomotic leak (OR 2.87, 95% CI 1.01-8.18; P =
0.048), respectively. CONCLUSIONS: Blood transfusion, perforating disease and
previous resection were significant risk factors for overall complications, intra
abdominal sepsis and anastomotic leak after ileocolonic resection for Crohn's
disease, respectively. Preoperative immunosuppressive or biologic therapy did not
increase the risk of postoperative complications.
PMID- 28408997
TI - Endoscopic balloon dilatation of Crohn's-associated intestinal strictures: High
patient satisfaction and long-term efficacy.
AB - INTRODUCTION: Stricture formation is a common long-term complication of Crohn's
disease. Endoscopic balloon dilatation offers a bowel-sparing treatment option,
but long-term outcome and its association with patient-, stricture-, and
procedure-related factors is only poorly understood. Patient satisfaction with
endoscopic balloon dilatation is largely unknown. METHODS: We performed a
retrospective review of all endoscopic balloon dilatation for Crohn's disease
related strictures between January 2005 and January 2013. Long-term outcome,
complication rates and predictive factors were evaluated. Patient satisfaction
was assessed using a questionnaire and telephone interviews. RESULTS: A total of
118 balloon dilatations were performed for 69 strictures in 46 patients. One
patient was excluded from further analysis due to malignancy. Median time from
diagnosis of Crohn's disease to symptomatic stricture formation was 19 years.
Technical success, defined as passage of the endoscope after dilatation, was
reportedly obtained in 95 of 106 procedures (89.6%). Two perforations occurred,
one of which could be managed conservatively. No episodes of severe bleeding were
recorded (procedure-related complication rate: 2/118; 1.7%). During a median
follow-up of 4.8 years (range 0.4-8.7), 55.6% (25/45) of patients were able to
avoid surgery. Of the patients, 35.6% (16/45) did not need any further
intervention, 40.0% (18/45) underwent more than one dilatation, and 24.4% (11/45)
were operated after the first dilatation. The percentage of patients who were
satisfied with the procedure and would again opt for balloon dilation as first
line therapy was 83.3% (35/42). None of the risk factors examined in this study
correlated with the necessity for subsequent surgery. DISCUSSION: Endoscopic
balloon dilatation is a safe and effective first line therapy for Crohn's disease
related strictures. No technical, stenosis-, or patient-related factor reliably
predicted sustained dilatation success. Patient satisfaction was high.
PMID- 28408999
TI - UEG Week Vienna 2016 award winners.
PMID- 28408998
TI - Reflecting on a highly successful UEG Week 2016.
PMID- 28408859
TI - Measurement of the [Formula: see text] production cross section using events in
the [Formula: see text] final state in pp collisions at [Formula: see text].
AB - The cross section of top quark-antiquark pair production in proton-proton
collisions at [Formula: see text] is measured by the CMS experiment at the LHC,
using data corresponding to an integrated luminosity of 2.2[Formula: see text].
The measurement is performed by analyzing events in which the final state
includes one electron, one muon, and two or more jets, at least one of which is
identified as originating from hadronization of a b quark. The measured cross
section is [Formula: see text], in agreement with the expectation from the
standard model.
PMID- 28409001
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1177/2050640616635957.].
PMID- 28409000
TI - Leadership roles for women in gastroenterology: New initiatives for the new
generation of gastroenterologists.
PMID- 28409002
TI - Erratum.
AB - [This corrects the article DOI: 10.1177/2050640614546947.].
PMID- 28409003
TI - 'Collinsella phocaeensis' sp. nov., 'Clostridium merdae' sp. nov., 'Sutterella
massiliensis' sp. nov., 'Sutturella timonensis' sp. nov., 'Enorma phocaeensis'
sp. nov., 'Mailhella massiliensis' gen. nov., sp. nov., 'Mordavella massiliensis'
gen. nov., sp. nov. and 'Massiliprevotella massiliensis' gen. nov., sp. nov., 9
new species isolated from fresh stool samples of healthy French patients.
AB - Here we report of summary of the characteristics of 'Collinsella phocaeensis'
strain Marseille-P3245T sp. nov., 'Clostridium merdae' strain Marseille-P2953T,
'Sutterella massiliensis' strain Marseille-P2435T sp. nov., 'Sutturella
timonensis' strain Marseille-P3282T sp. nov., 'Enorma phocaeensis' Marseille
P3242T sp. nov., 'Mailhella massiliensis' strain Marseille-P3199T gen. nov., sp.
nov., 'Mordavella massiliensis' strain Marseille-P3246T sp. nov. and
'Massiliprevotella massiliensis' strain Marseille-P2439T sp. nov. isolated from
fresh stool samples of healthy French patients.
PMID- 28409006
TI - Analysis of weekend effect on 30-day mortality among patients with acute
myocardial infarction.
AB - OBJECTIVES: Several publications have demonstrated increased 30-day mortality in
patients admitted on Saturdays or Sundays compared with weekdays. We sought to
determine whether this was true for two different cohorts of patients admitted
with acute myocardial infarction (MI). METHODS AND RESULTS: Thirty-day mortality
data were obtained for 3757 patients who had been admitted to the Belfast Health
and Social Care Trust with acute MI between 2009 and 2015. They were subdivided
into those presenting with ST elevation MI (n=2240) and non-ST elevation MI (n=
1517). We observed no excess 30-day mortality in those admitted over weekends.
CONCLUSION: Excess mortality in patients admitted at weekends is not a universal
finding. This may mean that that there are patient subgroups with proportionately
greater weekend hazard and points to the need for more detailed understanding of
the weekend effect.
PMID- 28409004
TI - Effect of beta-blockade on lung function, exercise performance and dynamic
hyperinflation in people with arterial vascular disease with and without COPD.
AB - INTRODUCTION: beta Blockers are important treatment for ischaemic heart disease
and heart failure; however, there has long been concern about their use in people
with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic
worsening of breathlessness. Despite growing evidence of safety and efficacy,
they remain underused. We examined the effect of beta-blockade on lung function,
exercise performance and dynamic hyperinflation in a group of vascular surgical
patients, a high proportion of who were expected to have COPD. METHODS: People
undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially
recruited from vascular surgery clinic. They completed plethysmographically
measured lung function and incremental cardiopulmonary exercise testing with
dynamic measurement of inspiratory capacity while taking and not taking beta
blocker. RESULTS: 48 participants completed tests while taking and not taking
beta blockers with 38 completing all assessments successfully. 15 participants
(39%) were found to have, predominantly mild and undiagnosed, COPD. People with
COPD had airflow obstruction, increased airway resistance (Raw) and specific
conductance (sGaw), static hyperinflation and dynamically hyperinflated during
exercise. In the whole group, beta-blockade led to a small fall in FEV1 (0.1
L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation.
No difference in response to beta-blockade was seen in those with and without
COPD. CONCLUSIONS: In people with AAA, beta-blockade has little effect on lung
function and dynamic hyperinflation in those with and without COPD. In this
population, the prevalence of COPD is high and consideration should be given to
case finding with spirometry. TRIAL REGISTRATION NUMBER: NCT02106286.
PMID- 28409005
TI - Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease.
AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a significant cause
of morbidity in persons living with HIV (PLWH) and HIV appears to uniquely cause
COPD, independent of smoking. The mechanisms by which HIV leads to COPD are not
clear. The objective of this study was to identify metabolomic biomarkers and
potential mechanistic pathways of HIV-associated COPD (HIV-COPD). METHODS: We
performed case-control metabolite profiling via mass spectrometry in plasma from
38 individuals with HIV-COPD (cases), comparing to matched controls with/without
HIV and with/without COPD. Untargeted metabolites of interest were identified
with liquid chromatography with mass spectrometry (LC-MS/mass spectrometry (MS)),
and targeted metabolomics for tryptophan (Trp) and kynurenine (Kyn) were measured
by selective reaction monitoring (SRM) with LC-MS/MS. We used mixed-effects
models to compare metabolite concentrations in cases compared with controls while
controlling for relevant biological variables. RESULTS: We identified 1689
analytes associated with HIV-COPD at a false discovery rate (FDR) of 10%. In
PLWH, we identified 263 analytes (10% FDR) between those with and without COPD.
LC MS/MS identified Trp and 17 lipids, including sphingolipids and
diacylglycerol. After adjusting for relevant covariates, the Kyn/Trp ratio
measured by SRM was significantly higher in PLWH (p=0.022), but was not
associated with COPD status (p=0.95). CONCLUSIONS: There is a unique metabolite
profile in HIV-COPD that includes sphingolipids. Trp metabolism is increased in
HIV, but does not appear to independently contribute to HIV-COPD. TRIAL
REGISTRATION NUMBERS: NCT01810289, NCT01797367, NCT00608764.
PMID- 28409007
TI - Subclinical sleep apnoea and plasma levels of endothelin-1 among young and
healthy adults.
AB - OBJECTIVE: Obstructive sleep apnoea (OSA) is a risk factor for vascular disease
and other adverse outcomes. These associations may be at least partly due to
early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED). Therefore, we
assessed the relationships between subclinical sleep apnoea and plasma levels of
ET-1. METHODS: We performed a population-based study among 1255 young and healthy
adults aged 25-41 years. Cardiovascular disease, diabetes or a body mass index
>35 kg/m2 were exclusion criteria. Plasma levels of ET-1 were measured using a
high-sensitivity, single-molecule counting technology. The relationships between
subclinical sleep apnoea (OSA indices: respiratory event index (REI), oxygen
desaturation index (ODI), mean night-time blood oxygen saturation (SpO2)) and ET
1 levels were assessed by multivariable linear regression analysis. RESULTS:
Median age of the cohort was 35 years. Median ET-1 levels were 2.9 (IQR 2.4-3.6)
and 2.5 pg/mL (IQR 2.1-3.0) among patients with (n=105; 8%) and without
subclinical sleep apnoea (REI 5-14), respectively. After multivariable
adjustment, subclinical sleep apnoea remained significantly associated with
plasma levels of ET-1 (beta=0.13 (95% CI 0.06 to 0.20) p=0.0002 for a REI 5-14;
beta=0.10 (95% CI 0.03 to 0.16) p=0.003 for an ODI>=5). Every 1% decrease in mean
night-time SpO2 increased ET-1 levels by 0.1 pg/mL, an association that remained
significant after multivariable adjustment (beta=0.02 (95% CI 0.003 to 0.033)
p=0.02). CONCLUSIONS: In this study of young and healthy adults, we found that
participants with subclinical sleep apnoea had elevated plasma ET-1 levels, an
association that was due to night-time hypoxaemia. Our results suggest that ED
may already be an important consequence of subclinical sleep apnoea.
PMID- 28409008
TI - Two-year outcome after early or late Intervention in non-ST elevation acute
coronary syndrome.
AB - OBJECTIVE: To compare long-term outcome of an early to a delayed invasive
strategy in high-risk patients with non-ST elevation acute coronary syndrome
(NSTE-ACS). METHODS: This prospective, multicentre trial included patients with
NSTE-ACS and at least two out of three of the following high-risk criteria: (1)
evidence of extensive myocardial ischaemia on ECG, (2) elevated biomarkers for
myocardial necrosis and (3) age above 65 years. Patients were randomised to
either an early (angiography and revascularisation if appropriate <12 hours) or a
delayed invasive strategy (>48 hours after randomisation). Endpoint for this
prespecified long-term follow-up was the composite incidence of death or
reinfarction after 2 years. Data collection was performed by telephone contact
with the patients, their relatives or general practitioner and by review of
hospital records. RESULTS: Endpoint status after 2-year follow-up was collected
in 521 of 542 initially enrolled patients. Incidence of death or reinfarction was
11.8% in the early and 13.1% in the delayed treatment group (relative risk
(RR)=0.90, 95% CI 0.57 to 1.42). No significant differences were found in
occurrence of the individual components of the primary endpoint: death 6.1% vs
8.9%, RR 0.69 (95% CI 0.37 to 1.27), reinfarction 6.5% vs 5.4%, RR 1.20 (95% CI
0.60 to 2.38). Post-hoc subgroup analysis showed statistical significant
interaction between age and treatment strategy on outcome (p=0.02). CONCLUSIONS:
After 2 years follow-up, no difference in incidence of death or reinfarction was
seen between early to late invasive strategy. These findings are in line with
results of other studies with longer follow-up. Older patients seem to benefit
more from early invasive treatment.
PMID- 28409009
TI - Prognosis of complete versus incomplete revascularisation of patients with STEMI
with multivessel coronary artery disease: an observational study.
AB - OBJECTIVE: The best strategy in patients with acute ST-segment elevation
myocardial infarction (STEMI) with multivessel coronary artery disease (CAD)
regarding completeness of revascularisation of the non-culprit lesion(s) is still
unclear. To establish which strategy should be followed, survival rates over a
longer period should be evaluated. The aim of this study was to investigate
whether complete revascularisation, compared with incomplete revascularisation,
is associated with reduced short-term and long-term all-cause mortality in
patients with first STEMI and multivessel CAD. METHODS: This retrospective study
consisted of 518 patients with first STEMI with multivessel CAD. Complete
revascularisation (45%) was defined as the treatment of any significant coronary
artery stenosis (>=70% luminal narrowing) during primary or staged percutaneous
coronary intervention prior to discharge. The primary end point was all-cause
mortality. RESULTS: Incomplete revascularisation was not independently associated
with 30-day all-cause mortality in patients with acute first STEMI and
multivessel CAD (OR 1.98; 95% CI 0.62to6.37; p=0.25). During a median long-term
follow-up of 6.7 years, patients with STEMI with multivessel CAD and incomplete
revascularisation showed higher mortality rates compared with patients who
received complete revascularisation (24% vs 12%, p<0.001), and these differences
remained after excluding the first 30 days. However, in multivariate analysis,
incomplete revascularisation was not independently associated with increased all
cause mortality during long-term follow-up in the group of patients with STEMI
who survived the first 30 days post-STEMI (HR 1.53 95% CI 0.89-2.61, p=0.12).
CONCLUSION: In patients with acute first STEMI and multivessel CAD, incomplete
revascularisation compared with complete revascularisation was not independently
associated with increased short-term and long-term all-cause mortality.
PMID- 28409010
TI - Specialist intervention is associated with improved patient outcomes in patients
with decompensated heart failure: evaluation of the impact of a multidisciplinary
inpatient heart failure team.
AB - OBJECTIVE: The study aimed to evaluate the impact of a multidisciplinary
inpatient heart failure team (HFT) on treatment, hospital readmissions and
mortality of patients with decompensated heart failure (HF). METHODS: A
retrospective service evaluation was undertaken in a UK tertiary centre
university hospital comparing 196 patients admitted with HF in the 6 months prior
to the introduction of the HFT (pre-HFT) with all 211 patients seen by the HFT
(post-HFT) during its first operational year. RESULTS: There were no significant
differences in patient baseline characteristics between the groups. Inpatient
mortality (22% pre-HFT vs 6% post-HFT; p<0.0001) and 1-year mortality (43% pre
HFT vs 27% post-HFT; p=0.001) were significantly lower in the post-HFT cohort.
Post-HFT patients were significantly more likely to be discharged on loop
diuretics (84% vs 98%; p=<0.0001), ACE inhibitors (65% vs 76%; p=0.02), ACE
inhibitors and/or angiotensin receptor blockers (83% vs 91%; p=0.02), and
mineralocorticoid receptor antagonists (44% vs 68%; p<0.0001) pre-HFT versus post
HFT, respectively. There was no difference in discharge prescription rates of
beta-blockers (59% pre-HFT vs 63% post-HFT; p=0.45). The mean length of stay
(17+/-19 days pre-HFT vs 19+/-18 days post-HFT; p=0.06), 1-year all-cause
readmission rates (46% pre-HFT vs 47% post-HFT; p=0.82) and HF readmission rates
(28% pre-HFT vs 20% post-HFT; p=0.09) were not different between the groups.
CONCLUSIONS: The introduction of a specialist inpatient HFT was associated with
improved patient outcome. Inpatient and 1-year mortality were significantly
reduced. Improved use of evidence-based drug therapies, more intensive diuretic
use and multidisciplinary care may contribute to these differences in outcome.
PMID- 28409011
TI - Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death
in hypertrophic cardiomyopathy.
AB - OBJECTIVE: Sudden cardiac arrest (SCA) is the most devastating outcome in
hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the
surface electrocardiogram (ECG) to identify the potential risk factors for SCA.
METHODS: Data was collected from 52 patients with HCM who underwent implantable
cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG
closest to the time of ICD implant were utilised for measuring the Tpeak-Tend
interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence
of the five traditional SCA-associated risk factors was assessed, as well as the
HCM risk-SCD score. RESULTS: 16 (30%) patients experienced aborted cardiac arrest
over 8.5+/-4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On
univariate analysis, T-wave amplitude was associated with appropriate ICD therapy
(HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated
with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT
ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed
T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per
0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead
V2 to the traditional risk factors resulted in significant improvement in risk
stratification (C-statistic from 0.65 to 0.75) but did not improve the
performance of the HCM SCD-risk score. CONCLUSIONS: T-wave amplitude is a novel
marker of SCA in this high risk HCM population and may provide incremental
predictive value to established risk factors. Further work is needed to define
the role of repolarisation abnormalities in predicting SCA in HCM.
PMID- 28409012
TI - Enhancing the diagnosis of fabry disease in cardiology with a targeted
information: a before-after control-impact study.
AB - BACKGROUND: Cardiac complications in Fabry disease are frequent and dominated by
a high frequency of left ventricular hypertrophy; therefore, cardiologists may
have an essential role in screening for this disease. Providing cardiologists
with targeted information on Fabry disease would be valuable and could reduce
both diagnostic and therapeutic delays. The aim of this study was to evaluate the
efficiency of such strategy for Fabry screening. METHODS: We conducted a before
after control-impact study by comparing observations made before and after
targeted information on Fabry disease among cardiologists. The information on
Fabry disease consisted of (1) an educational booklet, (2) oral information and
(3) screening kits. The programme was evaluated at the end of a 12-month study
period. RESULTS: Forty-two cardiologists participated to this study. None of them
had conducted screening test and new diagnostic for Fabry disease in the 3 years
prior the information. After the information, screening with dried blood spots
was performed in 55 patients (ranged 18-77 years, men: 39) with cardiac
monitoring for supposed sarcomeric hypertrophic cardiomyopathy (n=41) or
unexplained left ventricular hypertrophy (n=14) from January 2015 to January
2016. Two new cases of Fabry disease were diagnosed (3.4%) in two men (ages 58
and 51 years). The information was deemed relevant in both content and structure
and was deemed useful for everyday practice. CONCLUSION: Cardiologists valued the
targeted information on Fabry disease. This information had a direct clinical
impact by allowing the diagnosis of two new families with Fabry disease.
PMID- 28409013
TI - Lay beliefs about hypertension among HIV-infected adults in Kenya.
AB - OBJECTIVE: Hypertension affects 23% of Kenyans and is the most prevalent
modifiable risk factor for cardiovascular disease. Despite this, hypertension
awareness and treatment adherence is very low. We conducted a qualitative study
to explore lay beliefs about hypertension among HIV-infected adults to inform the
development of culture sensitive hypertension prevention and control program.
METHODS: Eight focus group discussions were held for 53 HIV-infected adults at
the HIV clinic in Kenya. RESULTS: Respondents had difficulties in describing
hypertension. Hypertension was considered a temporary illness that is fatal and
more serious than HIV. Stress was perceived as a main cause for hypertension with
a large majority claiming stress reduction as the best treatment modality.
Alcohol and tobacco use were not linked to hypertension. Obesity was cited as a
cause of hypertension but weight control was not considered as a treatment
modality even though the majority of our participants were overweight. Most
participants did not believe hypertension could be prevented. CONCLUSION: Our
findings suggest a limited understanding of hypertension among people living with
HIV and points to an urgent need to integrate hypertension education programmes
in HIV care facilities in Kenya. To effect change, these programmes will need to
tie in the culture meaning of hypertension.
PMID- 28409014
TI - Comparable effect of aliskiren or a diuretic added on an angiotensin II receptor
blocker on augmentation index in hypertension: a multicentre, prospective,
randomised study.
AB - BACKGROUND: The effects of antihypertensive drug combination therapy on central
blood pressure (BP) and augmentation index (AI) have not been fully elucidated.
We investigated the effects of the direct renin inhibitor, aliskiren, or a
diuretic added to an angiotensin II receptor blocker on AI in patients with
essential hypertension. METHODS: A 24-week, prospective, multicentre, randomised,
open-label study enrolled 103 patients already treated with valsartan.
Participants were randomly allocated to receive either valsartan with aliskiren
(V+A), or valsartan with trichlormethiazide (V+T). The primary outcome was the
change in AI derived from radial artery tonometry. Secondary outcome measures
included systolic and diastolic BP, cardio-ankle vascular index (CAVI, which
reflects arterial stiffness) and urinary 8-hydroxydeoxyguanosine concentration.
RESULTS: After 24 weeks, systolic and diastolic BP were significantly reduced in
both groups to a broadly comparable extent. There was no significant difference
in AI at the end of the study between the V+A group and the V+T group (between
group difference: -2.3%, 95% CI -6.9% to 2.2%, p=0.31). Central BP at the end of
the study also did not differ between the two groups (p=0.62). There was no
significant difference in the CAVI between the groups at the end of the study.
Urinary 8-hydroxydeoxyguanosine concentration was significantly lower in the V+A
group than in the V+T group (p<0.01), suggesting that V+A attenuated oxidative
stress more than V+T. CONCLUSION: The combination of valsartan and aliskiren had
an effect on AI comparable with that of the combination of valsartan and
trichlormethiazide. UMIN CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005726.
PMID- 28409015
TI - Use of SLICC criteria in a large, diverse lupus registry enables SLE
classification of a subset of ACR-designated subjects with incomplete lupus.
AB - OBJECTIVE: SLE is traditionally classified using the American College of
Rheumatology (ACR) criteria. The Systemic Lupus International Collaborating
Clinics (SLICC) recently validated an alternative system. This study examined
large cohorts of subjects with SLE and incomplete lupus erythematosus (ILE) to
compare the impact of ACR and SLICC criteria. METHODS: Medical records of
subjects in the Lupus Family Registry and Repository were reviewed for
documentation of 1997 ACR classification criteria, SLICC classification criteria
and medication usage. Autoantibodies were assessed by indirect immunofluorescence
(ANA, antidouble-stranded DNA), precipitin (Sm) and ELISA (anticardiolipin).
Other relevant autoantibodies were detected by precipitin and with a bead-based
multiplex assay. RESULTS: Of 3575 subjects classified with SLE under at least one
system, 3312 (92.6%) were classified as SLE by both systems (SLEboth), 85 only by
ACR criteria (SLEACR-only) and 178 only by SLICC criteria (SLESLICC-only). Of 440
subjects meeting 3 ACR criteria, 33.9% (149/440) were SLESLICC-only, while 66.1%
(n=291, designated ILE) did not meet the SLICC classification criteria. Under the
SLICC system, the complement criterion and the individual autoantibody criteria
enabled SLE classification of SLESLICC-only subjects, while SLEACR-only subjects
failed to meet SLICC classification due to the combined acute/subacute cutaneous
criterion. The SLICC criteria classified more African-American subjects by the
leucopenia/lymphopenia criterion than did ACR criteria. Compared with SLEACR-only
subjects, SLESLICC-only subjects exhibited similar numbers of affected organ
systems, rates of major organ system involvement (~30%: pulmonary,
cardiovascular, renal, neurological) and medication history. CONCLUSIONS: The
SLICC criteria classify more subjects with SLE than ACR criteria; however,
individuals with incomplete lupus still exist under SLICC criteria. Subjects who
gain SLE classification through SLICC criteria exhibit heterogeneous disease,
including potential major organ involvement. These results provide supportive
evidence that SLICC criteria may be more inclusive of SLE subjects for clinical
studies.
PMID- 28409017
TI - Observational studies on glucocorticoids are harmful!
PMID- 28409016
TI - Surface complement C3 fragments and cellular binding of microparticles in
patients with SLE.
AB - OBJECTIVES: To examine microparticles (MPs) from patients with SLE and healthy
controls (HCs) by determining the cellular origin of the MPs, quantifying
attached fragments of complement component 3 (C3) and assessing the ability of
MPs to bind to circulating phagocytes and erythrocytes. These features may be
relevant for clearance of MPs in SLE pathogenesis. METHODS: Attached C3 fragments
(C3b, iC3b, C3d), membrane integrity and cell surface markers of MPs from 18
patients with SLE and 11 HCs were measured by adding specific antibodies, 7
aminoactinomycin D (7AAD) and annexin V. MPs from all subjects were labelled with
carboxyfluorescein diacetate succinimidyl ester and allowed to bind to autologous
phagocytes and erythrocytes in the presence of autologous serum, and the binding
to individual cell populations was assessed by flow cytometry. RESULTS: The
proportion of MPs bearing C3 fragments was higher in patients with SLE than in
HCs (p=0.026), but the amount of opsonising C3b/iC3b molecules was lower
(p=0.004). The C3b/iC3b level correlated with the concentration of circulating C3
(rs=0.53, p=0.036). Phagocytes and erythrocytes from patients and HCs bound
autologous MPs, and granulocytes from patients bound 13% more MPs than those from
HCs (p=0.043). The presence of erythrocytes inhibited the MP binding to
granulocytes by approximately 50%. CONCLUSIONS: Our demonstration of altered
composition of C3 fragments on MPs from patients with SLE, including decreased
numbers of opsonising C3 fragments, and competitive binding of MPs to circulating
phagocytes and erythrocytes corroborates the hypothesis of defective clearance of
apoptotic material in SLE, and indicates that differences in both MP opsonisation
and binding of MPs to cells are important in the pathogenesis of SLE.
PMID- 28409018
TI - [The relationship between community resilience and adolescent smoking behavior].
AB - BACKGROUND AND OBJECTIVES: Our study investigates the theoretical and practical
relationship between community resilience and adolescent smoking behavior, based
on the assumption that experiencing the supportive, protective and regulatory
power of local communities and neighborhoods influences adolescent smoking
behavior, it delays the early testing and it reduces the prevalence of regular
smoking. The study is based on an ongoing research related to smoking prevention.
METHODS: Empirical, self-administered questionnaire based study, random,
stratified, multistage sample, delivered in Mures, Harghita and Covasna Counties,
Romania. RESULTS AND CONCLUSIONS: The community relationship showed significant
association with the smoking behavior, the risk of smoking was higher among those
young people who had less contact with the local community. There was a
significantly lower number of regular smokers among those adolescents who
perceived restrictions by their family and community in relation to smoking and
those with higher social capital.
PMID- 28409019
TI - [The need and possibility of community-based smoking prevention in Transylvania].
AB - The study is based on an ongoing joint research of the Targu Mures University of
Medicine and Pharmacy and Davidson College from USA related to smoking
prevention. Some of the objectives of the study in 3 Transylvanian counties were:
the assessment of adolescents' smoking habits, the proof of the need for
community prevention, the development of a methodology which applies to local
characteristics, and the implementation of a community-based prevention plan.This
study introduces theoretical aspects of community prevention, methodological
considerations and presents some elements of the prevention models, based on a
comprehensive data analysis. Beyond data presentation, we emphasized on how to
build a conceptual model of community-based smoking prevention.
PMID- 28409020
TI - MEDICAL SCIENCE, RESEARCH AND HIGHER EDUCATION IN AZERBAIJAN FROM BIOETHICAL
DEVELOPMENTS PERSPECTIVE.
AB - Azerbaijan is a modern, rapidly developing democratic country at the crossroads
of Europe and Asia. The country is currently harmonizing its national legislation
with international norms, and reforming its national scientific and medical.
Higher standards of medical research and education will enhance public health and
protect human rights to life and health that are specified in Azerbaijan
Constitution. In order to raise its medical research and education to
international standards, Azerbaijani scientists and authorities are studying the
experience of other countries and taking measures to implement international
standards and norms in the country's national legislation. Cooperation with the
WHO, UNESCO and other international and foreign organizations, both on regional
and global level is creating steps to achieve this goal. These steps include, for
example, creation of the Azerbaijan unit of the UNESCO Chair in Bioethics and
teaching bioethics based on UNESCO's Bioethics Core Curriculum. Another step is
providing research fellowship for young Azerbaijani professionals to study at
leading medical research and educational centers around the world including
Harvard Medical School and Boston Children's Hospital in the USA, and Koc
University in Turkey. A complementary step is the development of local bioethical
research, including its legal, ethical and scientific foundations. Adherence to
ethical principles in different spheres of life is currently one of the most
challenging social and professional issues, especially, this is true with the
development of new medical technologies in recent decades and the development of
new ethical and legal standards, issues involving different areas of health and
medicine and their relation to human rights. Bioethics in Azerbaijan is
developing as an important field that deals with universal moral principles
within the context of both national laws and the UNESCO Universal Declaration on
Bioethics and Human Rights.
PMID- 28409021
TI - Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral
Administration in Human Eyes.
AB - Purpose. This study was performed to measure the concentration of trans
resveratrol and its three metabolites in human eyes. Methods. The patients who
underwent pars plana vitrectomy for rhegmatogenous retinal detachment were
included. The participants were orally given trans-resveratrol-based supplement
(Longevinex(r)). A suitable amount of conjunctiva, aqueous humor, and vitreous
humor were obtained during the operation. High-performance liquid chromatography
(HPLC) with mass spectrometry (LC/MS/MS) was used to detect the concentration of
trans-resveratrol and its three metabolites in the various samples. Results. The
average concentration of resveratrol in the conjunctiva was 17.19 +/- 15.32
nmol/g (mean +/- SD). The concentration of resveratrol in the aqueous humor was
close to the limit of detection, but its metabolites could be quantified. The
concentrations of resveratrol metabolites in the aqueous humor can be detected.
In the vitreous humor, the average concentration of resveratrol-3-O-sulfate was
62.95 +/- 41.97 nmol/L. The sulfate conjugations of resveratrol were recovered in
the conjunctiva, aqueous humor, and vitreous humor. Conclusions. Resveratrol and
its three metabolites can be detected in the ocular tissues after oral
administration. Although the concentration of parent resveratrol was low in the
eyes, its metabolites could be detected and may have a role in the treatment of
ocular diseases.
PMID- 28409022
TI - The Safety and Efficacy of Adjustable Postoperative Position after Pars Plana
Vitrectomy for Rhegmatogenous Retinal Detachment.
AB - Purpose. To report the safety and efficacy of adjustable postoperative position
for rhegmatogenous retinal detachment (RRD). Methods. Retrospective review of 536
consecutive RRD eyes that underwent vitrectomy surgery for retina repair from
year 2008 to 2014. The retinal breaks were divided into superior, lateral (nasal,
temporal, and macular), and inferior locations, according to the clock of breaks.
Patients with superior and lateral break location were allowed to have facedown
position or lateral decubitus position postoperatively, while patients with
inferior break location were allowed to have facedown position. Results. 403 eyes
of 400 patients were included. The mean follow-up interval was 22.7 +/- 21.3
months. The overall primary retinal reattachment rate was 93.3%. There were 24
(6.0%), 273 (67.7%), and 106 (26.3%) patients with superior, lateral, and
inferior break location, respectively. The primary reattachment rate was 95.8%,
92.3%, and 95.3% accordingly. After further divided the break location into
subgroups as a function of duration of symptom, postoperative lens situation,
number of retinal breaks, and different vitreous tamponade, the primary
reattachment rates were all higher than 82%. Conclusion. Adjustable postoperative
positioning is effective and safe for RRD repair with different break locations.
Choosing postoperative position appropriately according to retinal break
locations could be recommended.
PMID- 28409023
TI - A New Sutureless Illuminated Macular Buckle Designed for Myopic Macular Hole
Retinal Detachment.
AB - Purpose. To report the anatomic and visual results of a new sutureless
illuminated macular buckle designed for patients with macular hole retinal
detachment related to high myopia (MMHRD). Design. Prospective nonrandomized
comparative interventional trial. Methods. Twenty myopic eyes of 20 patients
(mean age, 51.4 years; range, 35-65 years) presenting with MMHRD with a posterior
staphyloma, in whom the new buckle was used, were evaluated. The buckle used was
assembled from a 5 mm wide sponge and a 7 mm wide silicone tire; it was fixed
utilizing the sterile topical adhesive Histoacryl Blue (B Braun, TS1050044FP)
which polymerizes in seconds upon being exposed to water-containing substances.
The primary outcomes measured included aided visual acuity (BCVA) and optical
coherence tomography (OCT) findings. The mean follow-up period was 6 months.
Results. Postoperatively, the MH closure was identified by OCT in 8 (40%) eyes.
The mean BCVA increased from 0.11 to 0.21 (p < 0.005). The axial length of the
eyes included decreased from 30.5 mm preoperatively to 29.8 mm (p = 0.002)
postoperatively. Conclusion. Preparation of the new sutureless macular buckle is
simple and easy. Illumination of the terminal part of the buckle ensures proper
placement. Histoacryl Blue is effective in fixing the buckle in its place for at
least 6 months with no reported intra- or postoperative complications.
PMID- 28409024
TI - Response to: Comment on "Exotropia Is the Main Pattern of Childhood Strabismus
Surgery in the South of China: A Six-Year Clinical Review".
PMID- 28409025
TI - The Impact of the Menstrual Cycle on Perioperative Bleeding in Vitreoretinal
Surgery.
AB - Purpose. To investigate the effect of menstrual cycle on perioperative bleeding
of primary vitreoretinal surgery. Methods. Data on female patients who had
vitrectomy surgery was retrospectively collected. Exclusion criteria were history
of trauma, vitreous hemorrhage, previous vitreoretinal surgery, diabetic
retinopathy, endophthalmitis, acute retinal necrosis, single vitreous opacity,
and use of antiplatelet agents. Perioperative bleeding was defined as hemorrhage
in the iris, vitreous, choroidal, retina, or subretina during surgery or up to
one day postoperatively. 69 patients had surgery during the perimenstrual phase
(group M, days 1-7 and days 21-28) and 86 during periovulatory phase (group O,
days 8-20) were enrolled. Results. The proportion of operative bleeding in group
M (14.5%) and group O (10.5%) was not found to be significantly different (p =
0.45). No postoperative bleeding was recorded in both groups. The univariate odds
ratio (OR) and 95% confidence interval (CI) of perimenstrual phase for operative
bleeding were 0.69 (0.26-1.81). After adjusting for patients' age, vitreoretinal
diseases, and surgeons, the multivariate OR and 95% CI were 0.71 (0.27-1.86).
Conclusion. This study suggests that the timing of the menstrual period does not
affect perioperative bleeding for primary vitreoretinal surgery. Menstruation
appears not to be a contraindication for vitreoretinal surgery.
PMID- 28409026
TI - Antiretroviral Treatment Adherence: Knowledge and Experiences among Adolescents
and Young Adults in Soweto, South Africa.
AB - Human immunodeficiency virus (HIV) management of adolescents and young adults
(AYAs) is particularly pertinent to sub-Saharan Africa, where the pediatric HIV
burden is marked. Antiretroviral treatment (ART) adherence is a major challenge
for AYAs. This qualitative study explored knowledge and experiences of adherence
amongst AYAs attending treatment at the Perinatal HIV Research Unit (PHRU),
Soweto, South Africa. Four focus group discussions (FGDs) and eight in-depth
interviews (IDIs) were conducted with HIV-infected 15-25-year-old ART recipients.
Transcripts were coded thematically. Participants (n = 26) were aged median 18.5
years, 59.1% female and 69.2% virally suppressed <400 cp/ml. Three main themes
emerged during FGDs and IDIs: (i) correct knowledge about how to be adherent,
benefits, and nonadherence consequences, (ii) social, personal, and medication
related barriers to adherence, and (iii) reminder, concealment, and motivational
strategies to optimize adherence. Interventions to improve AYA adherence could
focus on practical strategies, including status disclosure and medication
concealment.
PMID- 28409027
TI - Male Partners Involvement in Prevention of Mother-to-Child Transmission of HIV
Services in Southern Central Ethiopia: In Case of Lemo District, Hadiya Zone.
AB - Male partners' involvement is a vital issue to prevent human immunodeficiency
virus (HIV) transmission from mother to child; because it is much expectable that
women were more vulnerable and high risk group of population portion. Therefore,
to save lives of mothers and their newborn from acquiring HIV, male partners
should do their maximum endeavor regardless of any determinant factors as our
results revealed its status in our study context and elsewhere at past time too.
PMID- 28409028
TI - Impact of Delayed Admission to the Intensive Care Unit from the Emergency
Department upon Sepsis Outcomes and Sepsis Protocol Compliance.
AB - Rationale. The impact of emergency department length of stay (EDLOS) upon sepsis
outcomes needs clarification. We sought to better understand the relationship
between EDLOS and both outcomes and protocol compliance in sepsis. Methods. We
performed a retrospective observational study of septic patients admitted to the
ICU from the ED between January 2012 and December 2015 in a single tertiary care
teaching hospital. 287 patients with severe sepsis and septic shock were
included. Study population was divided into patients with EDLOS < 6 hrs (early
admission) versus >=6 hours (delayed admission). We assessed the impact of EDLOS
on hospital mortality, compliance with sepsis protocol, and resuscitation.
Statistical significance was determined by chi-square test. Results. Of the 287
septic ED patients, 137 (47%) were admitted to the ICU in <6 hours. There was no
significant in-hospital mortality difference between early and delayed admissions
(p = 0.68). Both groups have similar compliance with the 3-hour protocol (p =
0.77). There was no significant difference in achieving optimal resuscitation
within 12 hours (p = 0.35). Conclusion. We found that clinical outcomes were not
significantly different between early and delayed ICU admissions. Additionally,
EDLOS did not impact compliance with the sepsis protocol with the exception of
repeat lactate draw.
PMID- 28409029
TI - Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding
Cassette Proteins.
AB - Although membrane proteins represent most therapeutically relevant drug targets,
the availability of atomic resolution structures for this class of proteins has
been limited. Structural characterization has been hampered by the biophysical
nature of these polytopic transporters, receptors, and channels, and recent
innovations to in vitro techniques aim to mitigate these challenges. One such
class of membrane proteins, the ATP-binding cassette (ABC) superfamily, are
broadly expressed throughout the human body, required for normal physiology and
disease-causing when mutated, yet lacks sufficient structural representation in
the Protein Data Bank. However, recent improvements to biophysical techniques
(e.g., cryo-electron microscopy) have allowed for previously "hard-to-study" ABC
proteins to be characterized at high resolution, providing insight into molecular
mechanisms-of-action as well as revealing novel druggable sites for therapy
design. These new advances provide ample opportunity for computational methods
(e.g., virtual screening, molecular dynamics simulations, and structure-based
drug design) to catalyze the discovery of novel small molecule therapeutics that
can be easily translated from computer to bench and subsequently to the patient's
bedside. In this review, we explore the utility of recent advances in biophysical
methods coupled with well-established in silico techniques towards drug
development for diseases caused by dysfunctional ABC proteins.
PMID- 28409030
TI - Effects of Multicomponent Exercise on Functional and Cognitive Parameters of
Hypertensive Patients: A Quasi-Experimental Study.
AB - Purpose. The present study aimed to investigate the impact of a 6-month
multicomponent exercise program (MCEP) on physical function and cognitive
parameters of normotensive (NTS) and hypertensive (HTS) older patients and verify
if age can influence the adaptations in response to the exercise. Methods. A
total of 218 subjects, 101 NTS and 117 HTS, were recruited and underwent
functional and cognitive evaluations before and after six months of a MCEP. The
program of exercise was performed twice a week, for 26 weeks. The physical
exercises were thought to mimic the activities of daily living and, therefore,
aggregated functional and walking exercises. Exercise sessions were performed at
moderate intensity. Results. Data indicated that HTS and NST patients showed a
similar increase in the performance of walking speed test and one-leg stand test
after the MCEP. Regarding age, results did not show differences in the magnitude
of adaptations between old and young HTS and NTS patients. Conclusions. Data of
the present study indicated that a 6-month MCEP was able to increase equally
balance and mobility in NTS and HTS patients. Moreover, data demonstrated that
aging did not seem to impair the capacity to adapt in response to exercise in
both groups.
PMID- 28409031
TI - Patient Perspectives on Engagement in Recovery after Hip Fracture: A Qualitative
Study.
AB - Purpose. To understand older adults' engagement in their recovery experience and
rehabilitation after a fall-related hip fracture. Method. 50 community-dwelling
older adults recovering from a recent (3-12 months) hip fracture (32 women, 18
men) participated in telephone interviews using a semistructured format at 6 and
12 months after recruitment into the study. Interviews were conducted as part of
a mixed-methods study designed to test the effect of a postoperative hip fracture
management program (B4 Clinic). Results. Three substantive themes were identified
in the qualitative data: (1) managing expectations; (2) engaging in physical
activity; and (3) there is life after fracture. Participants shared valuable
insight into how their expectations for their recovery period compared to their
lived experience and the role of physical activity in their ability to return to
their prefracture activities. Conclusions. Our findings reflect older adults'
expectations for recovery from hip fracture. Encouraging engagement in
rehabilitative exercises and addressing expectations prior to hospital discharge
may improve patients' adherence to rehabilitation programs, functional outcomes,
and postoperative quality of life. Implications for rehabilitation include the
necessity for early and ongoing engagement of rehabilitation professionals.
PMID- 28409033
TI - Aborted Sudden Cardiac Death in a Female Patient Presenting with Takotsubo-Like
Cardiomyopathy due to Epicardial Coronary Vasospasm.
AB - Takotsubo cardiomyopathy is characterized by apical ballooning of the left
ventricle (LV) in the absence of relevant coronary artery stenosis, which
typically occurs in elderly women after emotional stress. Catecholamine
cardiotoxicity, metabolic disturbance, and coronary microvascular impairment have
previously been proposed as underlying pathophysiologic mechanisms of takotsubo
cardiomyopathy, whereas myocardial stunning resulting from epicardial coronary
artery vasospasm is not generally accepted as a cause of takotsubo
cardiomyopathy. The prognosis of takotsubo cardiomyopathy is generally more
favourable compared to myocardial infarction; however, severe complications such
as rupture of the LV and life-threatening arrhythmias may occur. Herein, we
describe a case of an 84-year-old female, who presented with aborted sudden
cardiac death due to ventricular fibrillation. Echocardiography suggested LV
apical ballooning with severely impaired LV-function, so that takotsubo
cardiomyopathy was suspected. However, coronary angiography revealed epicardial
spasm of the left anterior ascending, which resolved after intracoronary
injection of 0.2 mg nitroglycerine. Cardiac magnetic resonance exhibited
subendocardial late enhancement and echocardiography showed normalization of LV
dysfunction during follow-up. The patient was put on conservative treatment with
nitrates and calcium inhibitors and ICD implantation were deferred.
PMID- 28409032
TI - Distinct Pattern of Microgliosis in the Olfactory Bulb of Neurodegenerative
Proteinopathies.
AB - The olfactory bulb (OB) shows early neuropathological hallmarks in numerous
neurodegenerative diseases, for example, in Alzheimer's disease (AD) and
Parkinson's disease (PD). The glomerular and granular cell layer of the OB is
characterized by preserved cellular plasticity in the adult brain. In turn,
alterations of this cellular plasticity are related to neuroinflammation such as
microglia activation, implicated in the pathogenesis of AD and PD, as well as
frontotemporal lobe degeneration (FTLD). To determine microglia proliferation and
activation we analyzed ionized calcium binding adaptor molecule 1 (Iba1)
expressing microglia in the glomerular and granular cell layer, and the olfactory
tract of the OB from patients with AD, PD dementia/dementia with Lewy bodies
(PDD/DLB), and FTLD compared to age-matched controls. The number of Iba1 and CD68
positive microglia associated with enlarged amoeboid microglia was increased
particularly in AD, to a lesser extent in FTLD and PDD/DLB as well, while the
proportion of proliferating microglia was not altered. In addition, cells
expressing the immature neuronal marker polysialylated neural cell adhesion
molecule (PSA-NCAM) were increased in the glomerular layer of PDD/DLB and FTLD
cases only. These findings provide novel and detailed insights into differential
levels of microglia activation in the OB of neurodegenerative diseases.
PMID- 28409034
TI - Increased Intracranial Pressure during Hemodialysis in a Patient with Anoxic
Brain Injury.
AB - Dialysis disequilibrium syndrome (DDS) is a serious neurological complication of
hemodialysis, and patients with acute brain injury are at increased risk. We
report a case of DDS leading to intracranial hypertension in a patient with
anoxic brain injury and discuss the subsequent dialysis strategy. A 13-year-old
girl was admitted after prolonged resuscitation from cardiac arrest. Computed
tomography (CT) revealed an inferior vena cava aneurysm and multiple pulmonary
emboli as the likely cause. An intracranial pressure (ICP) monitor was inserted,
and, on day 3, continuous renal replacement therapy (CRRT) was initiated due to
acute kidney injury, during which the patient developed severe intracranial
hypertension. CT of the brain showed diffuse cerebral edema. CRRT was
discontinued, sedation was increased, and hypertonic saline was administered,
upon which ICP normalized. Due to persistent hyperkalemia and overhydration,
ultrafiltration and intermittent hemodialysis were performed separately on day 4
with a small dialyzer, low blood and dialysate flow, and high dialysate sodium
content. During subsequent treatments, isolated ultrafiltration was well
tolerated, whereas hemodialysis was associated with increased ICP necessitating
frequent pauses or early cessation of dialysis. In patients at risk of DDS,
hemodialysis should be performed with utmost care and continuous monitoring of
ICP should be considered.
PMID- 28409035
TI - The Use of Coupled Plasma Filtration Adsorption in Traumatic Rhabdomyolysis.
AB - Severe musculoskeletal injuries induce the release of sarcoplasmic elements such
as muscle enzymes, potassium, and myoglobin in the systemic circulation. The
circulating myoglobin damages the glomerulus and renal tubules. Conventional
haemodialysis is not able to remove myoglobin, due to its high molecular weight
(17,8 kilodaltons [kDa]). We treated four traumatic rhabdomyolysis patients with
Coupled Plasma Filtration Adsorption (CPFA) in order to remove myoglobin followed
by 14 hours of Continuous Veno-Venous Hemofiltration (CVVH). During the
treatment, all patients showed clinical improvement with a decrease in muscular
(creatine kinase [CK] and myoglobin) and renal (creatinine and potassium) damage
indices. One patient, in spite of full renal recovery, died of cerebral
haemorrhage on the 26th day of hospital stay.
PMID- 28409036
TI - Pre- and Postsurgical Orthodontics in Patients with Moebius Syndrome.
AB - The authors report a combined orthodontic-surgical correction of an adult
patient's malocclusion affected by Moebius Syndrome (MS). The treatment was
conducted at the Dentistry Unit and the Maxillofacial Surgery Unit of the
University Hospital of Parma. Treatment of malocclusion was performed after the
correction of facial mimic mobility with smile surgery. The postoperative
stability and orthodontic results were good and the correction of the
morphological problems related to the syndrome was very satisfactory.
PMID- 28409037
TI - Retracted: A Rare Pathological Entity of Multiple Calcified Hyperplastic Dental
Follicles.
AB - [This retracts the article DOI: 10.1155/2016/4190827.].
PMID- 28409038
TI - A Foreign Body Granuloma of the Buccal Mucosa Induced by Honeybee Sting.
AB - A foreign body granuloma of the buccal mucosa induced by honeybee sting was
reported. The patient was an 82-year-old female who presented with a submucous
mass at the right buccal mucosa. The mass was 20 mm in diameter, elastically
firm, partly mobile without pain or tenderness, and covered with almost normal
mucosa. MR image did not delineate the lesion clearly. Under clinical diagnosis
of a benign tumor, the lesion was excised under local anesthesia. The excised
lesion was 14 * 11 * 9 mm in size and solid and yellowish in cut surface.
Histologically, the lesion consisted of granulomatous tissue with a few narrow,
curved, eosinophilic structures compatible with decomposed fragments of a
honeybee sting and was diagnosed as a foreign body granuloma, although the
patient did not recall being stung.
PMID- 28409039
TI - Endodontic Management of Teeth Juxtaposed to Haemangioma.
AB - Vascular anomalies are localized defects in the vasculature that may or may not
be present at birth. There are many types of vascular anomalies with different
aetiology and clinical picture and, therefore, require the combined expertise of
medical, radiological, and surgical specialities for its diagnosis and
management. The term "haemangioma" is used as a common generic label to
incorporate all types of vascular malformations. In this report, we describe a
case of two maxillary premolars, requiring endodontic therapy, in close proximity
to a haemangioma. The challenges encountered in the diagnosis and management of
the case are discussed.
PMID- 28409040
TI - A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Extensively Studied by
Flow Cytometry and Immunohistochemistry.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic
malignancy with aggressive clinical course and poor prognosis. Diagnosis is based
on detection of CD4+ CD56+, CD123high, TCL-1+, and blood dendritic cell antigen
2/CD303+ blasts, together with the absence of lineage specific antigens on tumour
cells. In this report we present a case of BPDCN presenting with extramedullary
and bone marrow involvement, extensively studied by flow cytometry and
immunohistochemistry, who achieved complete remission after acute lymphoblastic
leukemia like chemotherapy and allogeneic hematopoietic stem cell
transplantation.
PMID- 28409041
TI - Bilateral Facial Diplegia: A Rare Presenting Symptom of Lyme.
AB - Lyme disease is a common disease that is faced by the physician but also acts a
mimicker of many other disease processes. Facial palsies, especially bilateral,
are a relatively rare presenting symptom of Lyme disease and may warrant further
investigation. A thorough history and physical examination coupled with precision
testing may aid the physician when faced with a patient with the diagnostic
dilemma of facial diplegia.
PMID- 28409042
TI - Nephrologists Hate the Dialysis Catheters: A Systemic Review of Dialysis Catheter
Associated Infective Endocarditis.
AB - A 53-year-old Egyptian female with end stage renal disease, one month after start
of hemodialysis via an internal jugular catheter, presented with fever and
shortness of breath. She developed desquamating vesiculobullous lesions,
widespread on her body. She was in profound septic shock and broad spectrum
antibiotics were started with appropriate fluid replenishment. An echocardiogram
revealed bulky leaflets of the mitral valve with a highly mobile vegetation about
2.3 cm long attached to the anterior leaflet. CT scan of the chest, abdomen, and
pelvis showed bilateral pleural effusions in the chest, with triangular opacities
in the lungs suggestive of infarcts. There was splenomegaly with triangular
hypodensities consistent with splenic infarcts. Blood cultures repeatedly grew
Candida albicans. Despite parenteral antifungal therapy, the patient deteriorated
over the course of 5 days. She died due to a subsequent cardiac arrest. Systemic
review of literature revealed that the rate of infection varies amongst the
various types of accesses, and it is well documented that AV fistulas have a much
less rate of infection in comparison to temporary catheters. All dialysis units
should strive to make a multidisciplinary effort to have a referral process early
on, for access creation, and to avoid catheters associated morbidity.
PMID- 28409043
TI - Rare Presentation of Primary Extramedullary Plasmacytoma as Lip Lesion.
AB - Malignant plasma cell proliferation can be presented as part of disseminated
disease of multiple myeloma, as solitary plasmacytoma of bone, or in soft tissue
as extramedullary plasmacytoma. Extramedullary plasmacytomas represented
approximately 3% of all plasma cell proliferation. Approximately 80% of
extramedullary plasmacytomas occur in the head and neck region while the other 4%
occur in the skin and to a lesser extent in the lip. In this paper, we report a
rare case of primary cutaneous plasmacytoma involving the lip in a 65-year-old
male. The patient presented with a nonhealing lower lip sore for the past 3
years. Upon further workup, there was no evidence of multiple myeloma or light
chain disease. The patient was treated with radiation therapy and his last follow
up revealed no evidence of multiple myeloma or light chain disease.
PMID- 28409044
TI - Perioperative Anaphylaxis to Chlorhexidine during Surgery and Septoplasty.
AB - Chlorhexidine is an antiseptic and disinfectant used in surgical and clinical
practice since 1954 and is available in aqueous or alcoholic solutions 0.5%-4.0%
and has a broad-spectrum activity. Despite their widespread use, allergic
reactions with chlorhexidine are rarely reported. We describe a case of
anaphylaxis with chlorhexidine during a septoplasty, turbinectomy, and maxillary
sinusectomy. The patient presented with periorbital edema, hives, hypotension,
and wheezing. Immediately after the diagnosis of anaphylaxis promethazine,
hydrocortisone, and epinephrine were administered with immediate clinical
improvement. This case highlights the importance of assessing whether there is a
previous clinical history of hypersensitivity to chlorhexidine in patients who
will undergo surgical procedures.
PMID- 28409045
TI - Odontogenic Cyst with Verrucous Proliferation Exhibiting Melanin Pigmentation.
AB - Verrucous proliferation arising from odontogenic cysts is a rare entity. We
report an unusual case of an infected odontogenic cyst with verrucous
proliferation and melanin pigmentation in a 13-year-old male patient who
presented with an intraoral swelling in relation to impacted teeth 26 and 27. The
enucleated lesion was diagnosed as an odontogenic keratocyst and the patient died
within two years of presentation due to multiple recurrences. The clinical,
radiological, and microscopic features of the lesion are presented with an
attempt to discuss the etiopathogenesis. The case hereby reported is uncommon
with only eight cases reported in the literature.
PMID- 28409046
TI - On a Rare Cutaneous Metastasis from a Sacrococcygeal Chordoma.
AB - Chordomas are rare malignant tumors of notochordal origin and are rare locally
aggressive ones with a metastatic potential. The skin rarely is seen as
metastatic site. We describe a case of an adult woman with cutaneous metastasis
of a primary sacral chordoma excised ten years before, which appeared as a
painless cutaneous mass located in the dorsal region. Once removed, the surgical
specimen was formalin fixed and in paraffin embedded. Sections were stained with
haematoxylin-eosin, and histochemical and immunohistochemical investigations were
performed. Histologically, the neoplasia was characterized by cords or single
tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm
(the classic "physaliphorous cells"), and mild nuclear atypia. Mitotic activity
was scanty. At immunohistochemistry, the tumor cells were diffusely positive for
S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous
metastasis of chordoma was performed. This case illustrates a diagnostic
challenge because of the unusual presentation of an already rare tumor.
PMID- 28409047
TI - A Giant Cavernous Hemangioma of the Left Atrioventricular Groove.
AB - A 10-year-old Chinese female diagnosed with an asymptomatic giant cardiac
cavernous hemangioma was reported. The patient originally tended to observation
because this unusual cardiac tumoral mass was discovered incidentally during
routine health examination of transthoracic echocardiography. Over 5 years of
follow-up, the mass had enlarged obviously, and the patient visited our
outpatient clinic and was prone to excision. Subsequently, a total resection
surgery of the tumor was performed, and the tumor was found to be located on the
left atrioventricular groove with complete packing membrane. The patient was
discharged on postoperative day 4 and remains asymptomatic on last follow-up.
PMID- 28409048
TI - Laparoscopic Reduction and Closure of an Internal Hernia Secondary to Gynecologic
Surgery.
AB - Internal hernia is a rare cause of bowel obstruction which often requires
emergent surgery. In general, the preoperative diagnosis of internal hernia is
difficult. The pelvic cavity has various spaces with the potential to result in a
hernia, especially in females. In this report, we describe a patient with an
internal hernia secondary to previous gynecologic surgery. A 49-year-old woman
presented with acute abdominal pain and a history of previous right oophorectomy
for a benign ovarian cyst. Computed tomography scan of the abdomen showed
obstruction with strangulation and emergent laparoscopic exploration was
performed. Intraoperatively, there was an incarcerated internal hernia in the
pelvis, located in the vesicouterine pouch, which was reduced. The orifice of the
hernia was a 2 cm defect caused by adhesions between the uterus and bladder. The
defect was closed with a continuous suture. The herniated bowel was viable, and
the operation was completed without intestinal resection. She was discharged four
days after surgery without complications. Laparoscopy is useful to diagnose bowel
obstruction in selected patients and may also be used for definitive therapy. It
is important to understand pelvic anatomy and consider an internal hernia of the
pelvic cavity in females, in the differential diagnosis of bowel obstruction,
especially those with a history of gynecological surgery.
PMID- 28409049
TI - Rivastigmine as a Symptomatic Treatment for Apathy in Parkinson's Dementia
Complex: New Aspects for This Riddle.
AB - Over 90% of PDD patients show at least one neuropsychiatric symptom (NPS); in the
60-70% two or more NPS are present. Their incidence is important in terms of
prognosis and severity of pathology. However, among all NPS, apathy is often the
most disturbing, associated with greater caregiver's burden. Similar to other
NPS, apathy may be due to a dysfunction of the nigrostriatal pathway, even
though, not all the PD patients become apathetic, indicating that apathy should
not entirely be considered a dopamine-dependent syndrome, and in fact it might
also be related to acetylcholine defects. Apathy has been treated in many ways,
without sure benefits; among these, Rivastigmine may present benefic properties.
We present a series of 48 patients, suffering from PDD, treated with
Rivastigmine, and followed-up for one year; they have been devotedly studied for
apathy, even though all the other NPS disorders have been registered.
Rivastigmine did not have a prolonged benefic effect on apathy, in our work, on
the contrary of what had been observed in the literature, probably due to the
longer follow-up of our patients.
PMID- 28409050
TI - Correlation of MRI Visual Scales with Neuropsychological Profile in Mild
Cognitive Impairment of Parkinson's Disease.
AB - Few studies have evaluated magnetic resonance imaging (MRI) visual scales in
Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD
patients and 92 controls (CO) to perform neurologic and neuropsychological
evaluation. Brain MRI was performed to evaluate the following scales: Global
Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis
revealed that both PD groups (amnestic and nonamnestic) showed worse performance
on several tests when compared to CO. Memory, executive function, and attention
impairment were more severe in amnestic PD-MCI group. Overall analysis of
frequency of MRI visual scales by MCI subtype did not reveal any statistically
significant result. Statistically significant inverse correlation was observed
between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive
Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test,
trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA
scale correlated with Stroop test and Fazekas scale with figure memory test,
digit span, and Stroop test according to the subgroup evaluated. Visual scales by
MRI in MCI should be evaluated by cognitive domain and might be more useful in
more severely impaired MCI or dementia patients.
PMID- 28409051
TI - Revisiting Hemicraniectomy: Late Decompressive Hemicraniectomy for Malignant
Middle Cerebral Artery Stroke and the Role of Infarct Growth Rate.
AB - Objective and Methods. The outcome in late decompressive hemicraniectomy in
malignant middle cerebral artery stroke and the optimal timings of surgery has
not been addressed by the randomized trials and pooled analysis. Retrospective,
multicenter, cross-sectional study to measure outcome following DHC under 48 or
over 48 hours using the modified Rankin scale [mRS] and dichotomized as favorable
<=4 or unfavorable >4 at three months. Results. In total, 137 patients underwent
DHC. Functional outcome analyzed as mRS 0-4 versus mRS 5-6 showed no difference
in this split between early and late operated on patients [P = 0.140] and
mortality [P = 0.975]. Multivariate analysis showed that age >= 55 years, MCA
with additional infarction, septum pellucidum deviation >=1 cm, and uncal
herniation were independent predictors of poor functional outcome at three
months. In the "best" multivariate model, second infarct growth rate [IGR2] >7.5
ml/hr, MCA with additional infarction, and patients with temporal lobe
involvement were independently associated with surgery under 48 hours. Both first
infarct growth rate [IGR1] and second infarct growth rate [IGR2] were nearly
double [P < 0.001] in patients with early surgery [under 48 hours]. Conclusions.
The outcome and mortality in malignant middle cerebral artery stroke patients
operated on over 48 hours of stroke onset were comparable to those of patients
operated on less than 48 hours after stroke onset. Our data identifies IGR,
temporal lobe involvement, and middle cerebral artery with additional infarct as
independent predictors for early surgery.
PMID- 28409052
TI - Job Satisfaction Analysis in Rural China: A Qualitative Study of Doctors in a
Township Hospital.
AB - Background. Township hospitals in China provide rural communities with basic but
much needed critical health care services. The doctors working in these hospitals
often feel unsatisfied when considering their work schedules and financial
rewards. Method. To explore job satisfaction of health workers in a township
hospital, a qualitative study was conducted of 39 doctors from five township
hospitals in Guangxi Zhuang Autonomous Region. The goal was to understand the
level of job satisfaction of doctors and to make recommendations for
improvements. Results. About 75% (28/39) of the doctors expressed negative
attitudes related to their work conditions. Slightly more than half (22/39)
mentioned they should receive greater compensation for their work and more than
one were seriously considering other options. Many participants (35/39) showed
their satisfaction about the achievement of serving as a doctor. Conclusion.
Their main concerns related to job satisfaction included working conditions,
financial rewards, and the doctor's relationships with patients. Increasing the
incomes and fringe benefits of healthcare workers, improving their work
conditions, and providing training and continuing education opportunities would
help rural clinics retain doctors and eliminate the current unsatisfactory
conditions. The findings also highlight the need for the government to increase
financial support of township hospitals.
PMID- 28409053
TI - Lessons learnt from a measles outbreak in Madang Province, Papua New Guinea, June
2014 - March 2015.
AB - OBJECTIVE: This study examined measles vaccine wastage during an outbreak
response in Madang Province of Papua New Guinea from June 2014 to March 2015.
METHODS: Vaccine wastage was defined as the number of doses received by a health
centre minus the total number of doses administered during and returned following
the outbreak vaccination campaign. Vaccine data were collected from the
Provincial Health Information Office, the Provincial Vaccine Store register and
clinic and health centre immunization registers for calculating the vaccine
wastage. Interviews were conducted with all 48 health centres involved in the
outbreak response using a structured questionnaire to explore the reasons for
vaccine wastage. RESULTS: Of the 154 110 doses issued by Madang Province during
the outbreak, a total of 85 236 (55%) doses were wasted. The wastage varied by
district from 31% to 90%. The total cost of the vaccine wastage was estimated to
be 589 810 Kina (US$ 196 604). None of the health centres maintained vaccine
stock registers. Most health centres indicated multiple failures in cold chain
logistics. Almost 40% of health centres reported incorrectly diluting vaccines.
The same percentage of health centres reported using incorrect injection
techniques. DISCUSSION: Regular audits of cold chain logistics, staff training
and improved processes for recording vaccine administration and wastage will
decrease vaccine wastage during vaccine-preventable disease outbreaks and also
benefit routine immunization activities.
PMID- 28409054
TI - Sudden increase in human infection with avian influenza A(H7N9) virus in China,
September-December 2016.
AB - Since the first outbreak of avian influenza A(H7N9) virus in humans was
identified in 2013, there have been five seasonal epidemics observed in China. An
earlier start and a steep increase in the number of humans infected with H7N9
virus was observed between September and December 2016, raising great public
concern in domestic and international societies. The epidemiological
characteristics of the recently reported confirmed H7N9 cases were analysed. The
results suggested that although more cases were reported recently, most cases in
the fifth epidemic were still highly sporadically distributed without any
epidemiology links; the main characteristics remained unchanged and the genetic
characteristics of virus strains that were isolated in this epidemic remained
similar to earlier epidemics. Interventions included live poultry market closures
in several cities that reported more H7N9 cases recently.
PMID- 28409055
TI - Enhanced surveillance for the Third United Nations Conference on Small Island
Developing States, Apia, Samoa, September 2014.
AB - The Ministry of Health in Samoa, in partnership with the Pacific Community,
successfully implemented enhanced surveillance for the high-profile Third United
Nations Conference on Small Island Developing States held concurrently with the
popular local Teuila festival during a widespread chikungunya outbreak in
September 2014. Samoa's weekly syndromic surveillance system was expanded to 12
syndromes and 10 sentinel sites from four syndromes and seven sentinel sites;
sites included the national hospital, four private health clinics and three
national health service clinics. Daily situation reports were produced and were
disseminated through PacNet (the e-mail alert and communication tool of the
Pacific Public Health Surveillance Network) together with daily prioritized line
lists of syndrome activity to facilitate rapid response and investigation by the
Samoan EpiNet team. Standard operating procedures for surveillance and response
were introduced, together with a sustainability plan, including a monitoring and
evaluation framework, to facilitate the transition of the mass gathering
surveillance improvements to routine surveillance. The enhanced surveillance
performed well, providing vital disease early warning and health security
assurance. A total of 2386 encounters and 708 syndrome cases were reported.
Influenza-like illness was the most frequently seen syndrome (17%). No new
infectious disease outbreaks were recorded. The experience emphasized: (1) the
need for a long lead time to pilot the surveillance enhancements and to maximize
their sustainability; (2) the importance of good communication between key
stakeholders; and (3) having sufficient staff dedicated to both surveillance and
response.
PMID- 28409056
TI - Establishing seasonal and alert influenza thresholds in Cambodia using the WHO
method: implications for effective utilization of influenza surveillance in the
tropics and subtropics.
AB - OBJECTIVE: To establish seasonal and alert thresholds and transmission intensity
categories for influenza to provide timely triggers for preventive measures or
upscaling control measures in Cambodia. METHODS: Using Cambodia's influenza-like
illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to
2015, three parameters were assessed to monitor influenza activity: the
proportion of ILI patients among all outpatients, proportion of ILI samples
positive for influenza and the product of the two. With these parameters, four
threshold levels (seasonal, moderate, high and alert) were established and
transmission intensity was categorized based on a World Health Organization
alignment method. Parameters were compared against their respective thresholds.
RESULTS: Distinct seasonality was observed using the two parameters that
incorporated laboratory data. Thresholds established using the composite
parameter, combining syndromic and laboratory data, had the least number of false
alarms in declaring season onset and were most useful in monitoring intensity.
Unlike in temperate regions, the syndromic parameter was less useful in
monitoring influenza activity or for setting thresholds. CONCLUSION: Influenza
thresholds based on appropriate parameters have the potential to provide timely
triggers for public health measures in a tropical country where monitoring and
assessing influenza activity has been challenging. Based on these findings, the
Ministry of Health plans to raise general awareness regarding influenza among the
medical community and the general public. Our findings have important
implications for countries in the tropics/subtropics and in resource-limited
settings, and categorized transmission intensity can be used to assess severity
of potential pandemic influenza as well as seasonal influenza.
PMID- 28409057
TI - Is population ageing cancelling out progress made in tuberculosis control in Hong
Kong Special Administrative Region SAR (China)? Age-adjusted analysis of case
notification data, 1990-2015.
PMID- 28409059
TI - Epidemiological and virological characteristics of seasonal influenza in the
Western Pacific Region of the World Health Organization, 2011-2015.
PMID- 28409058
TI - Exposure to H1 genotype measles virus at an international airport in Japan on 31
July 2016 results in a measles outbreak.
PMID- 28409060
TI - Visual Function and Its Relationship with Severity of Early, and Activity of
Neovascular, Age-Related Macular Degeneration.
AB - PURPOSE: To investigate the relationship between visual function and severity of
early age-related macular degeneration (AMD) and activity of neovascular (nv-)
AMD. METHODS: The following data was collected from 66 eyes of 66 subjects with
early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance
visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and
retinotopic ocular sensitivity (ROS) of the central 5 degrees of the retina, by
microperimetry. Fundus photographic grading of early AMD was performed in a
masked fashion. Mean foveal thickness (MFT) was measured by spectral domain
optical coherence tomography in patients with nv-AMD. RESULTS: In subjects with
early AMD, there was an inverse and statistically significant relationship
between measures of ROS within the central 5 degrees of retina (including
fixation) and severity of early AMD (p=0.01). In eyes with active nv-AMD, an
inverse and statistically significant relationship was observed between measures
of MFT and measures of ROS at the central 5 degrees of retina (r=-0.34; p=0.02).
No other measures, including CDVA, were significantly related to severity of
early AMD, or to MFT in nv-AMD. CONCLUSION: Although ROS was cross-sectionally
associated with disease severity, and inversely related to MFT, an important
determinant of need-to-treat in cases of nv-AMD, further research is required to
determine the appropriateness of ROS for monitoring early and active neovascular
forms of this disease.
PMID- 28409061
TI - Severe Hypoglycemia Associated with Tiapride in an Elderly Patient with Diabetes
and Psychosis.
PMID- 28409062
TI - Improved availability and quality of care with epilepsy nurse practitioners.
AB - BACKGROUND: This study investigated the quality of care delivered by nurse
practitioner (NP)-physician teams employed to expand clinic appointment
availability for patients with epilepsy. METHODS: We performed a retrospective
observational cohort study of patients with epilepsy presenting to the Penn
Epilepsy Center for a new patient appointment in 2014. During this time, patients
were seen either by an NP-physician team care model or a more traditional
physician-only care model. These care models were compared with regard to
adherence to the 2014 American Academy of Neurology epilepsy quality measures at
the initial visit. Clinical outcomes of seizure frequency, presentations to the
Emergency Department, injury, and death were assessed over the subsequent year.
RESULTS: A total of 169 patients were identified by our inclusion and exclusion
criteria: 65 patients in the NP-physician team care model cohort and 104 patients
in the physician-only care model cohort. The NP-physician team care model saw, on
average, 3 more patients per clinic session. There were no meaningful differences
between these cohorts in baseline characteristics. The NP-physician team care
model showed equivalent adherence to the physician-only care model for the
epilepsy quality measures, with superior adherence to the counseling measures of
querying for side effects, provision of personalized epilepsy safety education,
and screening for behavioral health disorders. The 2 care models performed
similarly in all clinical outcomes. CONCLUSIONS: An NP-physician team care model
employed to increase availability of care could also improve quality of care
delivered.
PMID- 28409064
TI - Value-Based Health Care Delivery, Preventive Medicine and the Medicalization of
Public Health.
AB - The real paradigm shift for healthcare is often stated to include a transition
from accentuating health care production and instead emphasize patient value by
moving to a 'value-based health care delivery'. In this transition, personalized
medicine is sometimes referred to as almost a panacea in solving the current and
future health challenges. In theory, the progress of precision medicine sounds
uncontroversial and most welcomed with its promise of a better healthcare for
all, with real benefits for the individual patient provided a tailored and
optimized treatment plan suitable for his or her genetic makeup. And maybe,
therefore, the assumptions underpinning personalized medicine have largely
escaped questioning. The use of personalized medicine and the use of digital
technologies is reshaping our health care system and how we think of health
interventions and our individual responsibility. However, encouraging individuals
to engage in preventive health activities possibly avoids one form of
medicalization (clinical), but on the other hand, it takes up another form
(preventive medicine and 'self-care') that moves medical and health concerns into
every corner of everyday life. This ought to be of little value to the individual
patient and public health. We ought to instead demand proof of these value ideas
and the lacking research. Before this is in place critical appraisal and cynicism
are requisite skills for the future. Otherwise, we are just listening to
visionaries when we put our future health into their hands and let personalized
solutions reach into people's everyday life regardless of patient safety and
integrity.
PMID- 28409063
TI - A practical approach to detection and treatment of depression in Parkinson
disease and dementia.
AB - PURPOSE OF REVIEW: To review the available evidence for the detection and
management of depression in Parkinson disease (PD) and dementia. RECENT FINDINGS:
Depression is a common comorbidity in those with PD or dementia, and leads to
increased morbidity. There are several available and accurate tools for the
detection of depression in PD (e.g., Geriatric Depression Scale) and dementia
(e.g., Cornell Scale for Depression in Dementia). Treatment of depression depends
on patient preference, severity of depression, comorbidities, and available
resources. Despite variable evidence, the use of nonpharmacologic strategies to
manage depression is suggested. Pharmacologic management is guided by modest
evidence in PD and dementia, but also informed by the management of late-life
depression (LLD). SUMMARY: There is evidence to guide the diagnosis and
management of depression in PD or dementia. However, more research is required in
this field to better inform clinical decision-making.
PMID- 28409065
TI - Malignant Clear Cell Hidradenoma of the Breast.
AB - A 58-year-old female had a mass in the right breast palpable beneath the areola.
A mammogram revealed a 1.5-centimeter soft tissue density that was confirmed with
a subsequent ultrasound. The patient underwent a core needle biopsy which was
initially reported as a moderately differentiated invasive ductal carcinoma.
Immunohistochemical analysis revealed negative staining for estrogen receptor
(ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2),
mammaglobin, and gross cystic disease fluid protein 15 (GCDFP-15). A wide local
excision of the mass was performed. The pathology report stated the tumor had an
infiltrative growth pattern with a desmoplastic stromal response with enhanced
epithelial atypia consistent with malignant transformation of a nodular clear
cell hidradenoma. Clear cell hidradenoma is a very rare tumor originating from
the sweat gland and has a propensity for the face and extremities. The malignant
variant of this tumor is extremely rare and has been reported to originate from
the breast in few cases. This case represents the difficulty in diagnosing this
tumor along with the radiographic and histologic features that can distinguish
this malignancy from other entities.
PMID- 28409066
TI - Giant Arachnoid Granulation Associated with Anomalous Draining Vein: A Case
Report.
AB - Giant arachnoid granulations (AG) can mimic intracranial lesions. Knowledge of
these structures can help avoid misdiagnosis when interpreting imaging. Here, we
report a child who presented with a mass within the superior sagittal sinus and
an anomalous draining vein. Herein, the diagnosis of a giant AG was made.
Clinicians who view or interpret imaging of the head should be aware of these
anatomical variants and though when very large, apparently, do not necessarily
result in pathology. Based on our case report, giant AG might also demonstrate
anomalous draining veins.
PMID- 28409067
TI - Lemmel Syndrome Secondary to Duodenal Diverticulitis: A Case Report.
AB - Lemmel syndrome occurs when a duodenal diverticulum causes obstructive jaundice
due to a mechanical obstruction of the common bile duct. Additional
pathophysiologic processes may also contribute to the development of Lemmel
syndrome. These include duodenal diverticula causing dysfunction of the sphincter
of Oddi as well as compression of the common bile duct by duodenal diverticula.
It is uncommon for duodenal diverticulum to become inflamed. We report the case
of a 25-year-old female presenting with unintentional weight loss and fatigue.
Since her initial labs were concerning for possible infection with hepatobiliary
abnormalities, a contrast-enhanced CT was obtained. This study revealed a large
periampullary diverticulum with mucosal enhancement and fat stranding consistent
with diverticulitis.
PMID- 28409068
TI - Redefining Health: Implication for Value-Based Healthcare Reform.
AB - Health definition consists of three domains namely, physical, mental, and social
health that should be prioritized in delivering healthcare. The emergence of
chronic diseases in aging populations has been a barrier to the realization of a
healthier society. The value-based healthcare concept seems in line with the true
health objective: increasing value. Value is created from health outcomes which
matter to patients relative to the cost of achieving those outcomes. The health
outcomes should include all domains of health in a full cycle of care. To
implement value-based healthcare, transformations need to be done by both health
providers and patients: establishing true health outcomes, strengthening primary
care, building integrated health systems, implementing appropriate health payment
schemes that promote value and reduce moral hazards, enabling health information
technology, and creating a policy that fits well with a community.
PMID- 28409069
TI - Efficiency of Crizotinib on an ALK-Positive Inflammatory Myofibroblastic Tumor of
the Central Nervous System: A Case Report.
AB - Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are
rare entities that have a predilection for local recurrences. Approximately half
of the inflammatory myofibroblastic tumors contain translocations that result in
the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby
present the case of a patient diagnosed with a left parieto-occipital IMT that
recurred after multiple surgeries and radiotherapy. Immuno-histochemical
examination of the tumor demonstrated ALK overexpression and the presence of an
ALK rearrangement observed in lung cancers. The patient was subsequently started
on an ALK inhibitor. A response evaluation criteria in solid tumors (RECIST)
partial response was observed by the seventh month of ALK inhibition and the
tumor remained in control for 14 months. The current case reiterates the activity
of ALK inhibitors within the CNS and suggests that radiotherapy may potentiate
the permeability of ALK inhibitors in CNS tumors addicted to ALK signalling.
PMID- 28409070
TI - A Rare Case of a Benign Primary Pleomorphic Adenoma of the Lung.
AB - Salivary gland tumors (SGT) constitute a small proportion of primary respiratory
system neoplasms. Benign SGT comprises pleomorphic adenoma and is exceedingly
rare in the lungs. We hereby present a rare case of a benign primary pleomorphic
adenoma of the lung. The histological pattern of the tumor was indistinguishable
from the head and neck SGT counterparts and showed biphasic morphology. Malignant
features were not observed and a metastatic SGT was ruled out. Although little is
known about the clinical progression of these rare tumors, surgical resection and
interval surveillance remains the treatment of choice.
PMID- 28409071
TI - Acute Cytomegalovirus (CMV) Infection Associated with Hemophagocytic
Lymphohistiocytosis (HLH) in an Immunocompetent Host Meeting All Eight HLH 2004
Diagnostic Criteria.
AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare and often deadly syndrome
characterized by severe inflammation and cytokine dysregulation. The disease is
defined by the HLH-2004 criteria, requiring five of eight findings, and is
further differentiated into either primary or secondary causes. Primary HLH tends
to be of genetic etiology, while secondary HLH results from other insults such as
infection. Secondary HLH is most commonly associated with viral infections in
immunocompromised patients. Acute cytomegalovirus (CMV) associated HLH in the
immunocompetent host is exceedingly rare and only documented in four case reports
to date. We describe the fifth documented case of CMV-associated HLH in an
immunocompetent patient, and furthermore, we demonstrate that this patient is the
first published case of its type to satisfy all eight of HLH-2004 criteria.
PMID- 28409072
TI - Reconceptualizing Benchmarks for Residency Training.
AB - Postgraduate medical education (PGME) is currently transitioning to a competency
based framework. This model clarifies the desired outcome of residency training -
competence. However, since the popularization of Ericsson's work on the effect of
time and deliberate practice on performance level, his findings have been applied
in some areas of residency training. Though this may be grounded in a noble
effort to maximize patient well-being, it imposes unrealistic expectations on
trainees. This work aims to demonstrate the fundamental flaws of this application
and therefore the lack of validity in using Ericsson's work to develop training
benchmarks at the postgraduate level as well as expose potential harms in doing
so.
PMID- 28409073
TI - Facial Paralysis and Hearing Loss: A Rare Manifestation of Prostate Cancer
Metastases.
AB - Dural prostate metastases (DPM) are a rare manifestation of metastatic prostate
cancer seen in approximately one to six percent of cases. Presenting symptoms may
include signs of elevated intracranial pressure, headache, altered mental status,
or cranial nerve palsies. Hearing loss, sensory changes, dysarthria, and
dysphagia are rare symptoms in DPM that were present in our patient. We present a
case of a 58-year-old male with a known diagnosis of adenocarcinoma of the
prostate presenting with symptoms of acute exacerbation of chronic obstructive
pulmonary disease (COPD), sub-acute right-sided hearing loss, and right-sided
facial paralysis. Over the course of hospitalization, his neurological symptoms
worsened and he developed dysarthria, dysphagia, facial numbness, and worsening
back pain. He also appeared more withdrawn and lethargic. The symptoms prompted a
neurological evaluation and a magnetic resonance imaging (MRI) revealed multiple
areas of bone marrow signal abnormality compatible with osseous metastatic
disease. There was extensive smooth dural thickening as well as focal nodular
thickening, both consistent with dural metastases. The patient was treated with
corticosteroids and external beam radiation therapy (EBRT) with improvement in
his back pain and facial paralysis. He died two weeks after completing EBRT.
Although rare, DPM should be suspected in males over 50 years of age presenting
with neurological symptoms. An MRI with gadolinium is most helpful in delineating
the presence and extent of dural and calvarial involvement. Corticosteroids and
EBRT have been shown to improve neurological function in up to 67% of patients.
However, median survival post-radiation remains approximately three months.
PMID- 28409074
TI - C2 and Greater Occipital Nerve: The Anatomic and Functional Implications in
Spinal Surgery.
AB - INTRODUCTION: Posterior C1-C2 fusion is a highly successful treatment for
atlantoaxial instability and other pathologies of the cervical spine, with fusion
rates approaching 95%-100%. However, poor visualization of the lateral masses of
C1 secondary to the course of the C2 nerve root along with blood loss from the
venous plexus and compression of the C2 nerve from lateral mass screws are
technical obstacles that can arise during surgery. Thus, sacrifice of the C2
nerve root has long since been debated in fusions involving the C1 and C2
vertebral bodies. METHODS: Cadaveric dissections on four adult specimens were
performed. Both intradural and extradural courses of C2 were studied in detail.
The tentative site of C2 nerve root compression during placement of C1 lateral
mass screws was studied in detail. Both the indication as well as the ease of C2
neurectomy were studied in relation to postoperative compression and entrapment.
RESULTS: Four-six dorsal rootlets of C2 nerve were observed while studying the
intradural course. The extradural course was studied with respect to the lateral
mass of C1. The greater occipital nerve (GON) course was fairly consistent in all
specimens. Transection of C2 around its ganglion would allow for proper C1
lateral mass screw placement as the course of C2 nerve interferes with proper
placement of instrumentation. CONCLUSION: C2 nerve root transection is associated
with occipital numbness but this often has no effect on health-related quality of
life (HRQOL). The C2 nerve root preservation is often associated with entrapment
neuropathy or occipital neuralgia, which greatly affects HRQOL. The C2 nerve root
transection helps in better visualization, aids in optimal placement of C1
lateral mass screws, minimizes estimated blood loss and improves surgical outcome
with successful fusion.
PMID- 28409075
TI - Bilateral Patella Dislocation after Total Knee Arthroplasty: A Report of Two
Cases and a Review of the Literature.
AB - Patellar instability is a known but catastrophic complication after total knee
arthroplasty (TKA). The occurrence of bilateral dislocation of the patella after
TKA is exceedingly rare. It may present as anterior knee pain, and diagnosis can
easily be made clinically or by plain radiographs. Early diagnosis with surgical
realignment and repair of the extensor mechanism can provide good outcomes after
this complication.
PMID- 28409076
TI - Memorial Issue for Professor Nobuhiko Saito.
PMID- 28409077
TI - Professor Nobuhiko Saito's contribution to statistical mechanics of biopolymers.
PMID- 28409078
TI - Statistical mechanics of protein structural transitions: Insights from the island
model.
AB - The so-called island model of protein structural transition holds that
hydrophobic interactions are the key to both the folding and function of
proteins. Herein, the genesis and statistical mechanical basis of the island
model of transitions are reviewed, by presenting the results of simulations of
such transitions. Elucidating the physicochemical mechanism of protein structural
formation is the foundation for understanding the hierarchical structure of life
at the microscopic level. Based on the results obtained to date using the island
model, remaining problems and future work in the field of protein structures are
discussed, referencing Professor Saito's views on the hierarchic structure of
science.
PMID- 28409079
TI - Characterization of protein folding by a Phi-value calculation with a statistical
mechanical model.
AB - The Phi-value analysis approach provides information about transition-state
structures along the folding pathway of a protein by measuring the effects of an
amino acid mutation on folding kinetics. Here we compared the theoretically
calculated Phi values of 27 proteins with their experimentally observed Phi
values; the theoretical values were calculated using a simple statistical
mechanical model of protein folding. The theoretically calculated Phi values
reflected the corresponding experimentally observed Phi values with reasonable
accuracy for many of the proteins, but not for all. The correlation between the
theoretically calculated and experimentally observed Phi values strongly depends
on whether the protein-folding mechanism assumed in the model holds true in real
proteins. In other words, the correlation coefficient can be expected to
illuminate the folding mechanisms of proteins, providing the answer to the
question of which model more accurately describes protein folding: the framework
model or the nucleation-condensation model. In addition, we tried to characterize
protein folding with respect to various properties of each protein apart from the
size and fold class, such as the free-energy profile, contact-order profile, and
sensitivity to the parameters used in the Phi-value calculation. The results
showed that any one of these properties alone was not enough to explain protein
folding, although each one played a significant role in it. We have confirmed the
importance of characterizing protein folding from various perspectives. Our
findings have also highlighted that protein folding is highly variable and unique
across different proteins, and this should be considered while pursuing a unified
theory of protein folding.
PMID- 28409080
TI - Cooperativity and modularity in protein folding.
AB - A simple statistical mechanical model proposed by Wako and Saito has explained
the aspects of protein folding surprisingly well. This model was systematically
applied to multiple proteins by Munoz and Eaton and has since been referred to as
the Wako-Saito-Munoz-Eaton (WSME) model. The success of the WSME model in
explaining the folding of many proteins has verified the hypothesis that the
folding is dominated by native interactions, which makes the energy landscape
globally biased toward native conformation. Using the WSME and other related
models, Saito emphasized the importance of the hierarchical pathway in protein
folding; folding starts with the creation of contiguous segments having a native
like configuration and proceeds as growth and coalescence of these segments. The
Phi-values calculated for barnase with the WSME model suggested that segments
contributing to the folding nucleus are similar to the structural modules defined
by the pattern of native atomic contacts. The WSME model was extended to explain
folding of multi-domain proteins having a complex topology, which opened the way
to comprehensively understanding the folding process of multi-domain proteins.
The WSME model was also extended to describe allosteric transitions, indicating
that the allosteric structural movement does not occur as a deterministic
sequential change between two conformations but as a stochastic diffusive motion
over the dynamically changing energy landscape. Statistical mechanical viewpoint
on folding, as highlighted by the WSME model, has been renovated in the context
of modern methods and ideas, and will continue to provide insights on equilibrium
and dynamical features of proteins.
PMID- 28409082
TI - What parameters characterize "life"?
AB - "Life" is a particular state of matter, and matter is composed of various
molecules. The state corresponding to "life" is ultimately determined by the
genome sequence, and this sequence determines the conditions necessary for
survival of the organism. In order to elucidate one parameter characterizing the
state of "life", we analyzed the amino acid sequences encoded in the total
genomes of 557 prokaryotes and 40 eukaryotes using a membrane protein prediction
online tool called SOSUI. SOSUI uses only the physical parameters of the encoded
amino acid sequences to make its predictions. The ratio of membrane proteins in a
genome predicted by the SOSUI online tool was around 23% for all genomes,
indicating that this parameter is controlled by some mechanism in cells. In order
to identify the property of genome DNA sequences that is the possible cause of
the constant ratio of membrane proteins, we analyzed the nucleotide compositions
at codon positions and observed the existence of systematic biases distinct from
those expected based on random distribution. We hypothesize that the constant
ratio of membrane proteins is the result of random mutations restricted by the
systematic biases inherent to nucleotide codon composition. A new approach to the
biological sciences based on the holistic analysis of whole genomes is discussed
in order to elucidate the principles underlying "life" at the biological system
level.
PMID- 28409081
TI - Itinerary profiling to analyze a large number of protein-folding trajectories.
AB - Understanding how proteins fold through a vast number of unfolded states is a
major subject in the study of protein folding. Herein, we present itinerary
profiling as a simple method to analyze molecular dynamics trajectories, and
apply this method to Trp-cage. In itinerary profiling, structural clusters
included in a trajectory are represented by a bit sequence, and a number of
trajectories, as well as the structural clusters, can be compared and classified.
As a consequence, the structural clusters that characterize the foldability of
trajectories were able to be identified. The connections between the clusters
were then illustrated as a network and the structural features of the clusters
were examined. We found that in the true folding funnel, Trp-cage formed a left
handed main-chain topology and the Trp6 side-chain was located at the front of
the main-chain ring, even in the initial unfolded states. In contrast, in the
false folding funnel of the pseudo-native states, in which the Trp6 side-chain is
upside down in the protein core, Trp-cage had a right-handed main-chain topology
and the Trp side-chain was at the back. The initial topological partition, as
determined by the main-chain handedness and the location of the Trp residue,
predetermines Trp-cage foldability and the destination of the trajectory to the
native state or the pseudo-native states.
PMID- 28409083
TI - Theoretical analyses on a flipping mechanism of UV-induced DNA damage.
AB - As for UV-induced DNA damage, which may induce skin cancer in animals and growth
inhibition in plants, there are two types of photoproducts, namely cis-sin
cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4)
photoproducts. When they are to be repaired, base-flipping occurs, and they bind
to enzymes. However, this process remains relatively unknown at a molecular
level. We analyze conformation and interaction energy changes upon base-flipping
using classical molecular dynamics (CMD) simulations and ab initio electronic
structure calculations. CMD simulations starting with a CPD in the flipped-in and
flipped-out states showed that both states were unchanged for 500 ns, indicating
the flipped-in and flipped-out processes do not occur spontaneously (without any
help of the enzyme) after photo-damage. To deeply understand the reasons, we
investigated interaction energy changes among bases upon structure changes during
the flipped-in and flipped-out processes using Parallel Cascade Selection-MD
(PaCS-MD) simulations at 400 K, followed by a fragment molecular orbital (FMO)
method. The total inter-fragment interaction energy (IFIE) between CPD and other
bases at the flipped-in state is estimated to be -60.08 kcal/mol. In particular,
four bases strongly interact with CPD with interaction energies being -10.96,
13.70, -21.52, and -14.46 kcal/mol each. On the other hand, the total IFIE at the
obtained flipped-out state increased to -10.40 kcal/mol by partly losing hydrogen
bonds and pi-pi stacking interactions, respectively. These results clearly
indicate that the base-flipping process of DNA lesions occurs with the help of
external forces like interactions with appropriate enzymes such as photolyases.
PMID- 28409084
TI - Actin binding domain of filamin distinguishes posterior from anterior actin
filaments in migrating Dictyostelium cells.
AB - Actin filaments in different parts of a cell interact with specific actin binding
proteins (ABPs) and perform different functions in a spatially regulated manner.
However, the mechanisms of those spatially-defined interactions have not been
fully elucidated. If the structures of actin filaments differ in different parts
of a cell, as suggested by previous in vitro structural studies, ABPs may
distinguish these structural differences and interact with specific actin
filaments in the cell. To test this hypothesis, we followed the translocation of
the actin binding domain of filamin (ABDFLN) fused with photoswitchable
fluorescent protein (mKikGR) in polarized Dictyostelium cells. When ABDFLN-mKikGR
was photoswitched in the middle of a polarized cell, photoswitched ABDFLN-mKikGR
rapidly translocated to the rear of the cell, even though actin filaments were
abundant in the front. The speed of translocation (>3 MUm/s) was much faster than
that of the retrograde flow of cortical actin filaments. Rapid translocation of
ABDFLN-mKikGR to the rear occurred normally in cells lacking GAPA, the only
protein, other than actin, known to bind ABDFLN. We suggest that ABDFLN
recognizes a certain feature of actin filaments in the rear of the cell and
selectively binds to them, contributing to the posterior localization of filamin.
PMID- 28409085
TI - Mechanical properties of spindle poles are symmetrically balanced.
AB - The metaphase spindle is organized for accurate chromosome segregation. One of
the fundamental features of the spindle across the species is its symmetrical
shape; the spindle consists of two polar arrays of microtubules at both ends.
Although it has been suggested that the formation of the bipolar shape requires
force balance coordination by molecular motors, i.e., kinesins and dyneins,
quantitative analysis for the pole mechanics has not been conducted. Here, we
demonstrate that it is not only the shape but also the stiffness and microtubule
density of the pairs of pole regions are symmetrically balanced in single
spindles self-assembled in Xenopus egg extracts. We found that the inhibition of
dynein functions dramatically reduced the stiffness and microtubule density in
the pole region. By contrast, the inhibition of one of the kinesins, Eg5, which
is the antagonistic motor protein of dynein, increased the value of these
parameters. Moreover, the inhibition of both dynein and Eg5 recovered these
parameter values to those of non-treated spindle poles. We also found that, when
one pole structure was held widened with the use of two glass microneedles, the
opposite pole structure spontaneously widened, resulting in the formation of the
barrel-like shaped spindle. The values of stiffness and microtubule density in
the manipulated pole region decreased, following the spontaneous decrement of
those in the paired unmanipulated pole region. These results suggest that the
spindle possesses a mechanism to dynamically maintain its symmetry in mechanical
properties.
PMID- 28409086
TI - Kinetic characteristics of chimeric channelrhodopsins implicate the molecular
identity involved in desensitization.
AB - Channelrhodopsin (ChR)-1 and ChR2 were the first-identified members of ChRs which
are a growing subfamily of microbial-type rhodopsins. Light absorption drives the
generation of a photocurrent in cell membranes expressing ChR2. However, the
photocurrent amplitude attenuates and becomes steady-state during prolonged
irradiation. This process, called desensitization or inactivation, has been
attributed to the accumulation of intermediates less conductive to cations. Here
we provided evidence that the dark-adapted (DA) photocurrent before
desensitization is kinetically different from the light-adapted (LA) one after
desensitization, that is, the deceleration of both basal-to-conductive and
conductive-to-basal transitions. When the kinetics were compared between the DA
and LA photocurrents for the ChR1/2 chimeras, the transmembrane helices, TM1 and
TM2, were the determinants of both basal-to-conductive and conductive-to-basal
transitions, whereas TM4 may contribute to the basal-to-conductive transitions
and TM5 may contribute to the conductive-to-basal transitions, respectively. The
fact that the desensitization-dependent decrease of the basal-to-conductive and
conductive-to-basal transitions was facilitated by the TM1 exchange from ChR2 to
ChR1 and reversed by the further TM2 exchange suggests that the conformation
change for the channel gating is predominantly regulated by the interaction
between TM1 and TM2. Although the exchange of TM1 from ChR2 to ChR1 showed no
obvious influence on the spectral sensitivity, this exchange significantly
induced the desensitization-dependent blue shift. Therefore, the TM1 and 2 are
the main structures involved in two features of the desensitization, the
stabilization of protein conformation and the charge distribution around the
retinal-Schiff base (RSB+).
PMID- 28409087
TI - Favourable outcomes of a preventive screening and counselling programme for older
people in underprivileged areas in the Netherlands: The PRIMUS project.
AB - An aging population is associated with an increased prevalence of diabetes,
cardiovascular diseases and depression. Important aspects of programmes targeted
at older people are: to reach those at risk, effective screening, optimising
advice, and referral to local interventions. We examined the effect of a
preventive health consultation (PRIMUS), a multi-behavioural screening programme
for persons aged 55-74 years in primary care. In a multi-centre randomised
controlled trial, the effects of participating in the PRIMUS intervention were
compared to a comparison group receiving personalised summaries and advice by
postal mail, both preceded by a health risk assessment via a questionnaire. The
intervention consisted of a baseline health risk assessment, followed by a
preventive health consultation (after 4 weeks), and a follow-up visit (2 weeks
later) in the primary care centre. A newly developed web-based computer-tailored
programme supported the nurse practitioner during the consultation. Main outcomes
measures were awareness of, and compliance with referral advice for changing
unhealthy lifestyles. The PRIMUS preventive health consultation was successful in
older people at risk for cardio metabolic diseases compared to the comparison
group (compliance: RR 1.43; 95% CI 1.12-1.79; p < 0.05). The intervention was
less successful in older people at risk for mental health problems. This
preventive health consultation for older people resulted in positive changes in
unhealthy behaviours by optimising reach, raising awareness, motivating and
assisting individuals to change, and referring to local interventions.
PMID- 28409088
TI - City scale climate change policies: Do they matter for wellbeing?
AB - Climate change mitigation policies aim to reduce climate change through reducing
greenhouse gas (GHG) emissions whereas adaption policies seek to enable humans to
live in a world with increasingly variable and more extreme climatic conditions.
It is increasingly realised that enacting such policies will have unintended
implications for public health, but there has been less focus on their
implications for wellbeing. Wellbeing can be defined as a positive mental state
which is influenced by living conditions. As part of URGENCHE, an EU funded
project to identify health and wellbeing outcomes of city greenhouse gas emission
reduction policies, a survey designed to measure these living conditions and
levels of wellbeing in Kuopio, Finland was collected in December 2013. Kuopio was
the northmost among seven cities in Europe and China studied. Generalised
estimating equation modelling was used to determine which living conditions were
associated with subjective wellbeing (measured through the WHO-5 Scale). Local
greenspace and spending time in nature were associated with higher levels of
wellbeing whereas cold housing and poor quality indoor air were associated with
lower levels of wellbeing. Thus adaption policies to increase greenspace might,
in addition to reducing heat island effects, have the co-benefit of increasing
wellbeing and improving housing insulation.
PMID- 28409089
TI - Comparative effectiveness of guided weight loss and physical activity monitoring
for weight loss and metabolic risks: A pilot study.
AB - Many consumer-based physical activity monitors (PAMs) are available but it is not
clear how to use them to most effectively promote weight loss. The purpose of
this pilot study was to compare the effectiveness of a personal PAM, a guided
weight loss program (GWL), and the combination of these approaches on weight loss
and metabolic risk. Participants completed the study in two cohorts: Fall 2010
and Spring 2011. A sample of 72 obese individuals in the Ames, IA area were
randomized to one of 3 conditions: 1) (GWL, N = 31), 2) PAM, N = 29, or 3) a
combination group (PAM + GWL, N = 29). Weight and metabolic syndrome score
(MetS), computed from waist circumference (WC), BMI, blood pressure (BP), and
lipids were assessed at baseline and following an 8-week intervention. Weight was
also assessed four months later. Two-way (Group * Time) ANOVAs examined
intervention effects and maintenance. Effect sizes were used to compare magnitude
of improvements among groups. During the intervention, all groups demonstrated
significant improvements in weight and MetS (mean weight loss = 4.16 kg, p <
0.001). Mean weight continued to decline modestly during follow-up, with average
weight loss of 4.82 kg from baseline (p < 0.01). There were no group differences
for weight loss but the PAM + GWL group had significantly larger changes in MetS
score (d = 0.06-0.77). The use of PAM resulted in significant improvements in
weight and MetS that were maintained across a four-month follow-up. Evidence
suggests that the addition of GWL contributed to enhanced metabolic outcomes.
PMID- 28409090
TI - The SMARTER pilot study: Testing feasibility of real-time feedback for dietary
self-monitoring.
AB - Self-monitoring (SM) of food intake is central to weight loss treatment.
Technology makes it possible to reinforce this behavior change strategy by
providing real-time feedback (FB) tailored to the diary entry. To test the
feasibility of providing 1-4 daily FB messages tailored to dietary recordings via
a smartphone, we conducted a 12-week pilot randomized clinical trial in
Pittsburgh, PA in US in 2015. We compared 3 groups: SM using the Lose It!
smartphone app (Group 1); SM + FB (Group 2); and SM + FB + attending three in
person group sessions (Group 3). The sample (N = 39) was mostly white and female
with a mean body mass index of 33.76 kg/m2. Adherence to dietary SM was recorded
daily, weight was assessed at baseline and 12 weeks. The mean percentage of days
adherent to dietary SM was similar among Groups 1, 2, and 3 (p = 0.66) at 53.50%
vs. 55.86% vs. 65.33%, respectively. At 12 weeks, all groups had a significant
percent weight loss (p < 0.05), with no differences among groups (- 2.85% vs. -
3.14% vs. - 3.37%) (p = 0.95); 26% of the participants lost >= 5% of their
baseline weight. Mean retention was 74% with no differences among groups (p =
0.37). All groups adhered to SM at levels comparable to or better than other
weight loss studies and lost acceptable amounts of weight, with minimal
intervention contact over 12 weeks. These preliminary findings suggest this 3
group approach testing SM alone vs. SM with real-time FB messages alone or
supplemented with limited in-person group sessions warrants further testing in a
larger, more diverse sample and for a longer intervention period.
PMID- 28409091
TI - Pilot survey of a novel incentive to promote healthy behavior among school
children and their parents.
AB - Reversing the obesity epidemic has been a persistent global public health
challenge, particularly among low socioeconomic status populations and
racial/ethnic minorities. We developed a novel concept of community-based
incentives to approach this problem in such communities. Applying this concept,
we proposed a school intervention to promote obesity prevention in the U.S. We
conducted a pilot survey to explore attitudes towards this future intervention.
The survey was collected as a nonprobability sample (N = 137 school-aged children
(5-12 years)) in northern California in July 2013. We implemented multivariable
logistic regression analyses where the dependent variable indicated the intention
to participate in the future intervention. The covariates included the body mass
index (BMI) based weight categories, demographics, and others. We found that the
future intervention is expected to motivate generally-high-risk populations (such
as children and parents who have never joined a past health-improvement program
compared to those who have completed a past health-improvement program (the odds
ratio (OR) = 5.84, p < 0.05) and children with an obese/overweight parent (OR =
2.72, p < 0.05 compared to those without one)) to participate in future obesity
prevention activities. Our analyses also showed that some subgroups of high-risk
populations, such as Hispanic children (OR = 0.27, p < 0.05) and children
eligible for a free or reduced price meal program (OR = 0.37, p < 0.06), remain
difficult to reach and need an intensive outreach activity for the future
intervention. The survey indicated high interest in the future school
intervention among high-risk parents who have never joined a past health
improvement program or are obese/overweight. These findings will help design and
implement a future intervention.
PMID- 28409092
TI - The Search for a Lipid Trigger: The Effect of Salt Stress on the Lipid Profile of
the Model Microalgal Species Chlamydomonas reinhardtii for Biofuels Production.
AB - BACKGROUND: Algal cells produce neutral lipid when stressed and this can be used
to generate biodiesel. OBJECTIVE: Salt stressed cells of the model microalgal
species Chlamydomonas reinhardtii were tested for their suitability to produce
lipid for biodiesel. METHODS: The starchless mutant of C. reinhardtii (CC-4325)
was subjected to salt stress (0.1, 0.2 and 0.3 M NaCl) and transesterification
and GC analysis were used to determine fatty acid methyl ester (FAME) content and
profile. RESULTS: Fatty acid profile was found to vary under salt stress
conditions, with a clear distinction between 0.1 M NaCl, which the algae could
tolerate, and the higher levels of NaCl (0.2 and 0.3 M), which caused cell death.
Lipid content was increased under salt conditions, either through long-term
exposure to 0.1 M NaCl, or short-term exposure to 0.2 and 0.3 M NaCl. Palmitic
acid (C16:0) and linolenic acid (C18:3n3) were found to increase significantly at
the higher salinities. CONCLUSION: Salt increase can act as a lipid trigger for
C. reinhardtii.
PMID- 28409093
TI - First case of invasive Magnusiomyces capitatus infection in Slovakia.
AB - Magnusiomyces capitatus (previously known as Geotrichum capitatum or
Blastoschizomyces capitatus or Trichosporon capitatum) is a rare cause of fungal
infection in immunocompromised patients. Most of these cases (87%) have been
reported from the Mediterranean region, as it is extremely rare to recognize it
in other regions. Here we report a first case of disseminated M. capitatus
infection in Slovakia. The patient - 19 year old woman with myelodysplastic
syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell
transplantation. The infection occurred despite antifungal prophylaxis with
micafungin, which was in vitro sensitive to the yeast. The treatment according to
minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte
transfusions were administered. M. capitatus was cleared out from the
bloodstream. However, patient died of multiple organ failure. Autopsy showed
multiple lesions in organs, but did not prove presence of yeast by
histopathology. M. capitatus was confirmed by polymerase chain reaction from all
tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the
post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier
Ltd. All rights reserved.
PMID- 28409094
TI - Successful treatment of azole-resistant invasive aspergillosis in a bottlenose
dolphin with high-dose posaconazole.
AB - Invasive aspergillosis due to azole-resistant Aspergillus fumigatus is difficult
to manage. We describe a case of azole-resistant invasive aspergillosis in a
female bottlenose dolphin, who failed to respond to voriconazole and posaconazole
therapy. As intravenous therapy was precluded, high dose posaconazole was
initiated aimed at achieving trough levels exceeding 3 mg/l. Posaconazole serum
levels of 3-9.5 mg/l were achieved without significant side-effects. Follow-up
bronchoscopy and computed tomography showed complete resolution of the lesions.
PMID- 28409095
TI - Arthroscopic Piriformis Release-A Technique for Sciatic Nerve Decompression.
AB - Various techniques for piriformis muscle release have been published previously.
However, it is imperative we continue to improve on existing techniques as well
as develop new ones that may further optimize outcomes. Therefore, we aimed to
describe an endoscopic technique for the release of the piriformis muscle in
those with symptoms of sciatic nerve compression. Using the posterolateral
portal, we are able to perform a complete release of the piriformis from the
greater trochanter and the piriformis fossa with care to protect the external
rotators and the sciatic nerve. It is our belief that this technique can be
easily replicated by practitioners who read this technical note.
PMID- 28409096
TI - Ankle Arthroscopy With Microfracture for Osteochondral Defects of the Talus.
AB - Therapeutic arthroscopy with microfracture leads to fibrocartilaginous repair and
is an effective treatment of osteochondral lesions of the talus. A full
diagnostic arthroscopy is performed, and then attention is turned to the
osteochondral defect. We describe in detail patient positioning, ankle
distraction, portal placement, steps of the diagnostic arthroscopy, and the
technique of microfracture. We then discuss the special considerations to be
taken regarding the use of a distractor, protection of neurovascular structures,
and the indications for microfracture.
PMID- 28409097
TI - Arthroscopic Technique for Stabilization of Chronic Acromioclavicular Joint
Instability With Coracoclavicular and Acromioclavicular Ligament Reconstruction
Using a Gracilis Tendon Graft.
AB - We present an arthroscopic technique for stabilization of chronic
acromioclavicular (AC) joint instability using a transclavicular-transcoracoidal
button technique, combined with a coracoclavicular and AC ligament reconstruction
using the gracilis tendon. This arthroscopic technique achieves an anatomic
reduction of the clavicle without further implant removal. It ensures vertical
and horizontal stabilization of the AC joint. Using a horizontal drill hole
through the clavicle and looping the gracilis tendon graft around the coracoid
avoids weakening of the coracoid with the risk of fracture.
PMID- 28409098
TI - Endoscopic Rectus Abdominis and Prepubic Aponeurosis Repairs for Treatment of
Athletic Pubalgia.
AB - Review of the English orthopaedic literature reveals no prior report of
endoscopic repair of rectus abdominis tears and/or prepubic aponeurosis
detachment. This technical report describes endoscopic reattachment of an avulsed
prepubic aponeurosis and endoscopic repair of a vertical rectus abdominis tear
immediately after endoscopic pubic symphysectomy for coexistent recalcitrant
osteitis pubis as a single-stage outpatient surgery. Endoscopic rectus abdominis
repair and prepubic aponeurosis repair are feasible surgeries that complement
endoscopic pubic symphysectomy for patients with concurrent osteitis pubis and
expand the less invasive options for patients with athletic pubalgia.
PMID- 28409099
TI - Arthroscopic Excision of a Symptomatic Meso-acromiale.
AB - The surgical technique for the management of a symptomatic os acromiale remains
unclear. Several operative techniques have been described including open
excision, open reduction-internal fixation (ORIF), arthroscopic acromioplasty or
subacromial decompression, and arthroscopic excision. There are 4 types of os
acromiale, with the meso-acromion being the most common and difficult to treat.
The excision of a pre-acromion arthroscopically or in an open manner usually
produces satisfactory results. However, the open excision of a meso-acromion can
lead to persistent pain and deltoid weakness and atrophy. The management of a
meso-acromial fragment with ORIF can also result in persistent pain and deltoid
weakness and atrophy with nonunion of the fragments. The purpose of this article
is to describe an alternative surgical technique to open excision or ORIF when
presented with a symptomatic meso-acromiale.
PMID- 28409100
TI - Arthroscopic Technique for Treatment of Schatzker Type III Tibia Plateau
Fractures Without Fluoroscopy.
AB - Accurate reduction and maintenance of the stability with correct implant
positioning is critical for surgical treatment of tibial plateau fractures. Our
technique includes an arthroscopic reduction and fixation of Schatzker type III
tibial plateau fractures with a bulls-eye screw placement without fluoroscopy
control. With the arthroscopic guidance, an anterior cruciate ligament drill
guide is placed and a K-wire sent to the midpoint of the depressed fragment
through the guide at a 40 degrees angle to the coronal axis of the tibia. A
tunnel is created with the drill over the K-wire. The depressed fragment is
further augmented with gentle impacts over the K-wire. After arthroscopic
reduction control, an appropriate-sized iliac graft is pushed until it is below
the depressed fragment. The targeting device is adjusted at 130 degrees so that
it is parallel to the joint line and a K-wire sent through the device so that it
would pass just below the graft. The graft is then supported with cannulated
screws sent over the K-wire. This technique provides an arthroscopic reduction of
the chondral surface and precise placement of the rafting screws without
fluoroscopy.
PMID- 28409101
TI - Microdrilling Surgery Augmented With Intra-articular Bone Marrow Aspirate
Concentrate, Platelet-Rich Plasma, and Hyaluronic Acid: A Technique for Cartilage
Repair in the Knee.
AB - The ideal treatment of large full-thickness chondral lesions in the knee,
especially "kissing lesions" and osteoarthritis, has not been determined.
Microdrilling surgery augmented with injections of peripheral blood stem cells
and hyaluronic acid has been used to treat patients with a wide range of
articular cartilage disease including patients with bipolar lesions and joint
space narrowing. Excellent results in this difficult patient population have been
reported, and second-look biopsy has shown repair tissue very similar to native
hyaline cartilage. Because of Food and Drug Administration regulations, this
technique is not currently allowed in the United States. We describe a Food and
Drug Administration-compliant modification of this technique using microdrilling
augmented with intra-articular bone marrow aspirate concentrate, platelet-rich
plasma, and hyaluronic acid.
PMID- 28409102
TI - Dry Arthroscopic Excision of Dorsal Wrist Ganglion.
AB - Ganglions are common soft tissue masses of the hand. High recurrence rates are
associated with nonsurgical treatment; thus, excision is often indicated.
Arthroscopic excision and open excision have similar recurrence rates; however,
the latter is associated with prolonged healing time and increased scarring.
Recently, dry wrist arthroscopic techniques have been used. This technique allows
easier confirmation of complete ganglion removal, easier conversion to open
surgery, earlier return of motion, and stitch-less closure when compared with
traditional "wet" arthroscopic excision.
PMID- 28409104
TI - Multidirectional Shoulder Instability: Arthroscopic Labral Augmentation.
AB - Capsulolabral augmentation is one of the most used arthroscopic techniques to
address multidirectional instability of the shoulder. Given the thin and weak
capsule seen in the affected patients, reconstruction in this subset of patients
can be particularly challenging. This arthroscopic technique aims to reduce the
capsular volume and deepen the glenoid socket through the creation of a
particularly voluminous "bumper" along the glenoid bone. Increasing the depth of
the glenoid facilitates a concavity-compression stabilizing effect and,
therefore, shoulder stability, especially midrange stability. This technique aims
to augment the bump of the standard capsulolabral reconstruction by using a
resorbable surgical mesh derived from porcine skin.
PMID- 28409103
TI - Posterior Cruciate Ligament Reconstruction With Hamstring Tendons Using a
Suspensory Device for Tibial Fixation and Interference Screw for Femoral
Fixation.
AB - A technique for posterior cruciate ligament reconstruction is presented.
Autologous hamstring tendons are selected as a graft. An interference screw is
used for femoral fixation. A suspension device is used for tibial fixation to
bring the fixation closer to the articular end of the tibial tunnel. Single
diameter tunnels of the same diameter as the graft are created in an outside-in
direction.
PMID- 28409105
TI - Anatomic Single-Bundle Anterior Cruciate Ligament Reconstruction Using the
Modified Transtibial Technique.
AB - We present a technique for anterior cruciate ligament (ACL) reconstruction using
hamstring tendon autograft with a modified transtibial technique. Our modified
transtibial technique has the advantages of the conventional transtibial
technique that is familiar to surgeons and that allows the press-fit fixing and
enables us to make a relatively long femoral tunnel. To make the femoral tunnel
at the anatomic position, the triangular, funnel-shaped bony trough was made to
slip the eccentrically positioned guide pin into the anticipated anatomic center
with a free-hand technique after marking the anatomic ACL footprint using a
microfracture awl through the anteromedial portal. Gradual femoral reaming was
performed with knee angle changes, which reduces the chances of posterior wall
blowout, increases the femoral tunnel length, and avoids breakage of guide pin at
the bending point. Our modified transtibial technique is anticipated to provide a
more anatomic placement of the femoral tunnel during ACL reconstruction than the
previous traditional transtibial techniques.
PMID- 28409106
TI - Open Bankart Revisited.
AB - The surgical treatment of anterior shoulder instability can present a dilemma.
Historically, an open Bankart repair was the benchmark solution. Over the last
decade as surgeons became more arthroscopically savvy, the pendulum swung and a
paradigm shift occurred. However, more recent studies have challenged this trend
and, subsequently, revived interest in open repair. Thus, we feel it is critical
to provide a more contemporary stepwise description of a procedure that has
become essentially abandoned. The goal is to provide tips and pearls to achieve
optimal exposure and, ultimately, a robust repair for a notoriously challenging
operation.
PMID- 28409107
TI - A Transosseous Bone Bridge Repair for Posterior Horn Meniscal Root Tears During
Anterior Cruciate Ligament Reconstruction.
AB - Meniscal root tears occur in isolation or concurrently with ligamentous knee
injury and cause significantly altered knee mechanics with the loss of normal
meniscus hoop stress. This loss of normal meniscus function can result in
abnormal knee kinematics and, subsequently, more rapid degenerative changes of
the knee articular surface. In the setting of anterior cruciate ligament tear,
the posterolateral meniscus root is most commonly damaged. Several techniques
exist for meniscus root repair; however, none have been shown to be clearly
superior. We present a safe, effective, and reproducible arthroscopic transtibial
technique for posterior horn lateral meniscal root tears.
PMID- 28409108
TI - Hamstring Graft Biological Preparation for Anterior Cruciate Ligament
Reconstruction.
AB - The all-inside anterior cruciate ligament reconstruction (ACLR) success depends
on biologic integration of the graft in the bone tunnel. Sutures wrapping the
tendon in the bone tunnel may affect tendon-bone healing in shorter bone tunnels.
To achieve better graft integration, we propose a variation of the graft link
suture technique wherein the graft is linked chain-like to the femoral and tibial
TightRope (Arthrex), which increases the tendon-bone contact area by eliminating
sutures from the noose of the graft and thus may allow better graft integration.
PMID- 28409109
TI - Flexor Pollicis Longus Tendoscopy.
AB - The deep palmar spaces of the hand include the midpalmar space, the hypothenar
space, the thenar space, space of Parona, and the interdigital web spaces. There
are various communications between different spaces. These communications are of
clinical importance in explaining the spread of inflammatory, infectious, and
even neoplasic processes that involve this region. Surgical incision and drainage
of all potentially communicating spaces and compartments is mandatory in deep
hand infections. The purpose of this technical note is to describe the minimally
invasive approach of endoscopic drainage and debridement of the flexor pollicis
longus tendon sheath, radial bursa, and thenar space.
PMID- 28409110
TI - Anatomic Humeral Head Reconstruction With Fresh Osteochondral Talus Allograft for
Recurrent Glenohumeral Instability With Reverse Hill-Sachs Lesion.
AB - The treatment of recurrent glenohumeral instability, especially with a
concomitant bony lesion, remains challenging. This is especially true in the case
of posterior instability given its less common incidence. Moreover, the presence
of an engaging reverse Hill-Sachs lesion in combination with posterior
instability will result in the need for a more aggressive treatment option. In
comparison with a Hill-Sachs lesion, a reverse Hill-Sachs lesion features greater
chondral deficiency that must be addressed during treatment. We propose the talus
allograft as a potential allograft for treatment of an engaging reverse Hill
Sachs lesion. The superior articular surface of the talus may be used to
reconstruct the articular surface of the humeral head. In this technical note, we
describe our preferred primary technique for treatment of an engaging reverse
Hill-Sachs lesion with recurrent glenohumeral instability through use of a fresh
osteochondral talus allograft, as well as discuss the advantages and
disadvantages of this allograft option.
PMID- 28409111
TI - A Rare Case of Raoultella planticola Pneumonia: An Emerging Pathogen.
AB - Raoultella planticola (R. planticola), considered an environmental organism, is a
gram negative, motile, bacillus with phenotypic similarities to the genus
Klebsiella. The organism remains a rare cause of human infection with a few cases
reported in the literature. However, since its description in 1981 there have
been increasing rates of infections caused by R. planticola with reports of
conjunctivitis, liver abscess, cholangitis, pancreatitis, and necrotizing
fasciitis. More concerning are reports of carbapenemase-producing isolates which
have led to the only 2 mortalities associated with R. planticola infections. To
our knowledge, we report the third case of R. planticola pneumonia in an
immunocompromised patient with no known direct exposure to the reported risk
factors.
PMID- 28409112
TI - Plasticity of premotor cortico-muscular coherence in severely impaired stroke
patients with hand paralysis.
AB - Motor recovery in severely impaired stroke patients is often very limited. To
refine therapeutic interventions for regaining motor control in this patient
group, the functionally relevant mechanisms of neuronal plasticity need to be
detected. Cortico-muscular coherence (CMC) may provide physiological and
topographic insights to achieve this goal. Synchronizing limb movements to motor
related brain activation is hypothesized to reestablish cortico-motor control
indexed by CMC. In the present study, right-handed, chronic stroke patients with
right-hemispheric lesions and left hand paralysis participated in a four-week
training for their left upper extremity. A brain-robot interface turned event
related beta-band desynchronization of the lesioned sensorimotor cortex during
kinesthetic motor-imagery into the opening of the paralyzed hand by a robotic
orthosis. Simultaneous MEG/EMG recordings and individual models from MRIs were
used for CMC detection and source reconstruction of cortico-muscular connectivity
to the affected finger extensors before and after the training program. The upper
extremity-FMA of the patients improved significantly from 16.23 +/- 6.79 to 19.52
+/- 7.91 (p = 0.0015). All patients showed significantly increased CMC in the
beta frequency-band, with a distributed, bi-hemispheric pattern and considerable
inter-individual variability. The location of CMC changes was not correlated to
the severity of the motor impairment, the motor improvement or the lesion volume.
Group analysis of the cortical overlap revealed a common feature in all patients
following the intervention: a significantly increased level of ipsilesional
premotor CMC that extended from the superior to the middle and inferior frontal
gyrus, along with a confined area of increased CMC in the contralesional premotor
cortex. In conclusion, functionally relevant modulations of CMC can be detected
in patients with long-term, severe motor deficits after a brain-robot assisted
rehabilitation training. Premotor beta-band CMC may serve as a biomarker and
therapeutic target for novel treatment approaches in this patient group.
PMID- 28409114
TI - Clinical and neuropsychological changes after the disappearance of seizures in a
case of transient epileptic amnesia.
AB - We encountered a female patient with late-onset temporal lobe epilepsy who
presented with transient amnesia as the sole ictal manifestation, an accelerated
rate of forgetting daily life events, and a retrograde memory deficit. We
describe the memory function of the patient both before and after the
administration of antiseizure medication. After the patient's seizures were
controlled with antiseizure drugs, her neuropsychological memory performance
scores showed improvement. We presumed that the disappearance of seizures was
associated with a decrease in the accelerated rate of forgetting medication.
However, her lost memories were not recovered after the seizures were controlled
by antiseizure medication.
PMID- 28409113
TI - Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine
pathways in early Parkinson's disease.
AB - A progressive loss of dopamine neurons in the substantia nigra (SN) is considered
the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological
evidence however suggests that the axons of the nigrostriatal dopaminergic system
are the earliest target of alpha-synuclein accumulation in PD, thus the principal
site for vulnerability. Whether this applies to in vivo PD, and also to the
mesolimbic system has not been investigated yet. We used [11C]FeCIT PET to
measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and
mesolimbic systems, in 36 early PD patients (mean disease duration in months +/-
SD 21.8 +/- 10.7) and 14 healthy controls similar for age. We also performed
anatomically-driven partial correlation analysis to evaluate possible changes in
the connectivity within both the dopamine networks at an early clinical phase. In
the nigrostriatal system, we found a severe DAT reduction in the afferents to the
dorsal putamen (DPU) (eta2 = 0.84), whereas the SN was the less affected region
(eta2 = 0.31). DAT activity in the ventral tegmental area (VTA) and the ventral
striatum (VST) were also reduced in the patient group, but to a lesser degree
(VST eta2 = 0.71 and VTA eta2 = 0.31). In the PD patients compared to the
controls, there was a marked decrease in dopamine network connectivity between SN
and DPU nodes, supporting the significant derangement in the nigrostriatal
pathway. These results suggest that neurodegeneration in the dopamine pathways is
initially more prominent in the afferent axons and more severe in the
nigrostriatal system. Considering PD as a disconnection syndrome starting from
the axons, it would justify neuroprotective interventions even if patients have
already manifested clinical symptoms.
PMID- 28409115
TI - A metagenomic approach to decipher the indigenous microbial communities of
arsenic contaminated groundwater of Assam.
AB - Metagenomic approach was used to understand the structural and functional
diversity present in arsenic contaminated groundwater of the Ganges Brahmaputra
Delta aquifer system. A metagene dataset (coded as TTGW1) of 89,171 sequences
(totaling 125,449,864 base pairs) with an average length of 1406 bps was
annotated. About 74,478 sequences containing 101,948 predicted protein coding
regions passed the quality control. Taxonomical classification revealed abundance
of bacteria that accounted for 98.3% of the microbial population of the
metagenome. Eukaryota had an abundance of 1.1% followed by archea that showed
0.4% abundance. In phylum based classification, Proteobacteria was dominant
(62.6%) followed by Bacteroidetes (11.7%), Planctomycetes (7.7%), Verrucomicrobia
(5.6%), Actinobacteria (3.7%) and Firmicutes (1.9%). The Clusters of Orthologous
Groups (COGs) analysis indicated that the protein regulating the metabolic
functions constituted a high percentage (18,199 reads; 39.3%) of the whole
metagenome followed by the proteins regulating the cellular processes (22.3%).
About 0.07% sequences of the whole metagenome were related to genes coding for
arsenic resistant mechanisms. Nearly 50% sequences of these coded for the
arsenate reductase enzyme (EC. 1.20.4.1), the dominant enzyme of ars operon.
Proteins associated with iron acquisition and metabolism were coded by 2% of the
metagenome as revealed through SEED analysis. Our study reveals the microbial
diversity and provides an insight into the functional aspect of the genes that
might play crucial role in arsenic geocycle in contaminated ground water of
Assam.
PMID- 28409116
TI - prepare_taxa_charts.py: A Python program to automate generation of publication
ready taxonomic pie chart images from QIIME.
AB - QIIME (Quantitative Insights Into Microbial Ecology) is one of the most popular
open-source bioinformatics suite for performing metagenome, 16S rRNA amplicon and
Internal Transcribed Spacer (ITS) data analysis. Although, it is very
comprehensive and powerful tool, it lacks a method to provide publication ready
taxonomic pie charts. The script plot_taxa_summary.py bundled with QIIME generate
a html file and a folder containing taxonomic pie chart and legend as separate
images. The images have randomly generated alphanumeric names. Therefore, it is
difficult to associate the pie chart with the legend and the corresponding sample
identifier. Even if the option to have the legend within the html file is
selected while executing plot_taxa_summary.py, it is very tedious to crop a
complete image (having both the pie chart and the legend) due to unequal image
sizes. It requires a lot of time to manually prepare the pie charts for multiple
samples for publication purpose. Moreover, there are chances of error while
identifying the pie chart and legend pair due to random alphanumeric names of the
images. To bypass all these bottlenecks and make this process efficient, we have
developed a python based program, prepare_taxa_charts.py, to automate the
renaming, cropping and merging of taxonomic pie chart and corresponding legend
image into a single, good quality publication ready image. This program not only
augments the functionality of plot_taxa_summary.py but is also very fast in terms
of CPU time and user friendly.
PMID- 28409117
TI - Searching for active mobile genetic elements in dsRNA fraction of Pinus
sylvestris having witches broom abnormalities.
AB - The most common type of coniferous mobile genetic elements are retrotransposons.
Despite of their early positive impact on evolution of modern coniferous species
they can have a significant negative impact for Forestry and breeding. Breaking
genomic structural integrity mobile elements can cause phenotypic defects of
plants. In this regard, the study of the diversity of coniferous mobile genetic
elements is particularly interesting. In the present paper, we describe mobile
genetic elements in dsRNA fraction of Pinus sylvestris having witches broom
abnormalities. In result of assembled contigs analysis by RepeatMasker 70 mobile
genetic elements were identified. A 68 of that were retroelements. Most of
elements represented by Gypsy (16 contigs) and Copia (48 contigs). In 4 cases
retroelements specific to Pinus taeda were identified. In most cases fragments of
integrase (24), reverse transcriptase (22) and RNaseH (15) were identified.
Results of the study may be of interest for coniferous breeding and genetic
specialists. The raw data of these experiments have been deposited at NCBI under
the accession number SAMN06185845.
PMID- 28409118
TI - Isolated Streptococcus intermedius pulmonary nodules.
AB - Streptococcus intermedius, a member of the Streptococcal anginosus group of alpha
hemolytic streptococci, remains a notable infectious agent causing necrotizing
pneumonia and abscesses. We report a case of a young male with pulmonary nodules
found to have Streptococcus intermedius and no other underlying hepatic or dental
history who was treated with ceftriaxone and avoided surgical intervention. A
review of the literature reveals cases that are typically treated with a combined
surgical and medical approach. These same cases often involve middle aged to
elderly individuals who have a past history of tobacco use, alcoholic liver
cirrhosis and/or poor dentition. This case stands out given the patient's
atypical presentation.
PMID- 28409119
TI - Severe dengue due to secondary hemophagocytic lymphohistiocytosis: A case study.
AB - Dengue, transmitted by the mosquito Aedes aegypti affects millions of people
worldwide every year. Dengue induced hemophagocytic lymphohistiocytosis (HLH) is
a serious condition and may prove fatal if not detected early and treated
appropriately. Diagnosis of HLH is challenging and usually missed as clinical and
laboratory findings are nonspecific. Moreover, the pathophysiology of the
systemic inflammatory response syndrome and/or sepsis is remarkably similar to
HLH. Secondary HLH following infection by the dengue virus is now being
increasingly recognized as a cause of severe form of the disease. We report a
case of dengue associated HLH in an otherwise healthy person who deteriorated
during the course of hospitalization. A disproportionately high ferritin level
and persistent bicytopenia prompted investigations for HLH. Diagnosis of dengue
fever with virus-associated hemophagocytic syndrome was established according to
the diagnostic criteria laid down by the Histiocyte Society. We discuss the
diagnosis and management of this complex case and try to generate awareness about
dengue induced HLH as one of the possible causes for severe manifestations of
this infection.
PMID- 28409120
TI - Sunitinib Enables a Clinical and Pathological Complete Remission of Metastatic
Renal Cell Carcinoma (mRCC).
AB - Renal cell carcinoma (RCC) is the most common renal cancer, and has a poor
prognosis in individuals with metastases (mRCC). In this report, we describe a 48
year-old woman with unresectable multiple liver metastases and a colonic
metastasis of RCC who was treated with sunitinib in combination with hepatic
microwave ablation and obtained a clinical and pathological complete remission.
We consider that sunitinib combined with microwave ablation can prevent
unresectable hepatic metastases of RCC from evolving, and that sunitinib alone
can achieve clinical and pathological remission in patients with colonic
metastasis of RCC.
PMID- 28409121
TI - Penile Preservation With Subcutaneous Transposition During Fournier's Gangrene.
AB - A 50-year-old male with past medical history of diabetes mellitus presented with
extensive Fournier's Gangrene. He had a wide-spread area of involvement and the
wound vacuum placement involved the entirety of the phallus. We describe a
surgical technique where the penis can be diverted from the site of the wound to
allow for more secure wound vacuum placement and future reconstructive options.
PMID- 28409122
TI - A post-publication analysis of the idealized upper reference value of 2.5 mIU/L
for TSH: Time to support the thyroid axis with magnesium and iron especially in
the setting of reproduction medicine.
AB - Laboratory medicine approaches the evaluation of thyroid function mostly through
the single determination of the blood level of thyroid stimulating hormone (TSH).
Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This
suggestion has not been confirmed by recent clinical studies. These studies have
delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These
values are valid for both for the general population as well as in the setting of
fertility and pregnancy. Current biochemical evidence about the elements required
to maintain thyroid function shows that these not only include dietary iodine but
also magnesium, iron, selenium and coenzyme Q10. Iron is important for the
synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process
of iodine uptake; iodine has to be sufficiently present in the diet; selenium
acts through selenoproteins to protect the thyroid cell during hormone synthesis
and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As
a consequence, good clinical practice requires additional biochemical information
on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status.
Since these elements are also important for the maintenance of reproductive
function, we postulate that they constitute the connecting link between both
endocrine systems.
PMID- 28409124
TI - Hospital Dissemination of tst-1-Positive Clonal Complex 5 (CC5) Methicillin
Resistant Staphylococcus aureus.
AB - Methicillin-resistant Staphylococcus aureus (MRSA), is one of the most prevalent
clinical pathogens isolated from hospital settings, and has increasingly
identified in community settings. In China, the SCCmecIII-ST239 strains are
disseminated in different geographic regions, accounting for >75% of all MRSA
isolates in some national studies. Here we characterized 150 non-duplicate MRSA
isolates collected from February 2012 to May 2013 in a tertiary hospital in
Suzhou, Eastern China, to explore the molecular epidemiology. All isolates were
characterized by spa typing, SCCmec typing, and detection of genes encoding
Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST-1).
Representative genotypes were also subjected to multilocus sequence typing
(MLST). Antibiotic susceptibility testing was performed using BD PhoenixTM
Automated Microbiology System. Molecular typing identified 11 clonal complex (CC)
and 28 spa types, with the CC5-spa t002 (29.3%) and CC239-spa t037 (14.7%) being
the most prevalent. SCCmec types II, III, IV, and V were identified in 33.3,
21.3, 23.3, and 21.3% of all isolates, respectively. PVL genes (lukF/S-PV) were
detected in 11.3% of all isolates and from 6 CCs (5, 8, 59, 88, 239, and 398).
The TSST-1 gene (tst) was detected in 18.0% of the all isolates, predominantly in
CC5 (96.3%). All the tst-1-positve CC5 isolates were spa t002. Eighteen patients
died within 30 days of hospitalization, and the in-hospital 30-day mortality was
12.0%. Multivariable analysis showed that 60 years old (odds ratio [OR] = 7.2, P
= 0.026), cancer diagnosis (OR = 9.6, P = 0.022), and MRSA isolate carriage of
tst-1 (OR = 62.5, P < 0.001) were independent factors associated with 30-day
mortality. Our study revealed unique MRSA dissemination patterns in our hospital
in comparison to those of other regions in China. The finding that tst-1-positive
CC5 strains were associated with higher mortality highlights the need for strict
infection control measures in order to prevent further spread of these strains in
our hospital, as well as others.
PMID- 28409123
TI - Autophagy and the Cell Cycle: A Complex Landscape.
AB - Autophagy is a self-degradation pathway, in which cytoplasmic material is
sequestered in double-membrane vesicles and delivered to the lysosome for
degradation. Under basal conditions, autophagy plays a homeostatic function.
However, in response to various stresses, the pathway can be further induced to
mediate cytoprotection. Defective autophagy has been linked to a number of human
pathologies, including neoplastic transformation, even though autophagy can also
sustain the growth of tumor cells in certain contexts. In recent years, a
considerable correlation has emerged between autophagy induction and stress
related cell-cycle responses, as well as unexpected roles for autophagy factors
and selective autophagic degradation in the process of cell division. These
advances have obvious implications for our understanding of the intricate
relationship between autophagy and cancer. In this review, we will discuss our
current knowledge of the reciprocal regulation connecting the autophagy pathway
and cell-cycle progression. Furthermore, key findings involving nonautophagic
functions for autophagy-related factors in cell-cycle regulation will be
addressed.
PMID- 28409125
TI - Colibactin Contributes to the Hypervirulence of pks+ K1 CC23 Klebsiella
pneumoniae in Mouse Meningitis Infections.
AB - Klebsiella pneumoniae is the most common pathogen of community-acquired
meningitis in Taiwan. However, the lack of a physiologically relevant meningitis
model for K. pneumoniae has impeded research into its pathogenesis mechanism.
Based on the core genome MLST analyses, the hypervirulent K1 K. pneumoniae
strains, which are etiologically implicated in adult meningitis, mostly belong to
a single clonal complex, CC23. Some K1 CC23 K. pneumoniae strains carry a gene
cluster responsible for colibactin production. Colibactin is a small genotoxic
molecule biosynthesized by an NRPS-PKS complex, which is encoded by genes located
on the pks island. Compared to other hypervirulent K. pneumoniae which primarily
infect the liver, the colibactin-producing (pks+) K1 CC23 strains had significant
tropism toward the brain of BALB/c mice. We aimed in this study to develop a
physiologically relevant meningitis model with the use of pks+ K1 CC23 K.
pneumoniae. Acute meningitis was successfully induced in adult BALB/c male mice
through orogastric, intranasal, and intravenous inoculation of pks+ K1 CC23 K.
pneumoniae. Besides the typical symptoms of bacterial meningitis, severe DNA
damages, and caspase 3-independent cell death were elicited by the colibactin
producing K1 CC23 K. pneumoniae strain. The deletion of clbA, which abolished the
production of colibactin, substantially hindered K. pneumoniae hypervirulence in
the key pathogenic steps toward the development of meningitis. Our findings
collectively demonstrated that colibactin was necessary but not sufficient for
the meningeal tropism of pks+ K1 CC23 K. pneumoniae, and the mouse model
established in this study can be applied to identify other virulence factors
participating in the development of this life-threatening disease.
PMID- 28409127
TI - SBOT will be responsible for basic orthopedic formation.
PMID- 28409126
TI - Genomics and Comparative Genomic Analyses Provide Insight into the Taxonomy and
Pathogenic Potential of Novel Emmonsia Pathogens.
AB - Over the last 50 years, newly described species of Emmonsia-like fungi have been
implicated globally as sources of systemic human mycosis (emmonsiosis). Their
ability to convert into yeast-like cells capable of replication and extra
pulmonary dissemination during the course of infection differentiates them from
classical Emmonsia species. Immunocompromised patients are at highest risk of
emmonsiosis and exhibit high mortality rates. In order to investigate the
molecular basis for pathogenicity of the newly described Emmonsia species,
genomic sequencing and comparative genomic analyses of Emmonsia sp. 5z489, which
was isolated from a non-deliberately immunosuppressed diabetic patient in China
and represents a novel seventh isolate of Emmonsia-like fungi, was performed. The
genome size of 5z489 was 35.5 Mbp in length, which is ~5 Mbp larger than other
Emmonsia strains. Further, 9,188 protein genes were predicted in the 5z489 genome
and 16% of the assembly was identified as repetitive elements, which is the
largest abundance in Emmonsia species. Phylogenetic analyses based on whole
genome data classified 5z489 and CAC-2015a, another novel isolate, as members of
the genus Emmonsia. Our analyses showed that divergences among Emmonsia occurred
much earlier than other genera within the family Ajellomycetaceae, suggesting
relatively distant evolutionary relationships among the genus. Through
comparisons of Emmonsia species, we discovered significant pathogenicity
characteristics within the genus as well as putative virulence factors that may
play a role in the infection and pathogenicity of the novel Emmonsia strains.
Moreover, our analyses revealed a novel distribution mode of DNA methylation
patterns across the genome of 5z489, with >50% of methylated bases located in
intergenic regions. These methylation patterns differ considerably from other
reported fungi, where most methylation occurs in repetitive loci. It is unclear
if this difference is related to physiological adaptations of new Emmonsia, but
this question warrants further investigation. Overall, our analyses provide a
framework from which to further study the evolutionary dynamics of Emmonsia
strains and identity the underlying molecular mechanisms that determine the
infectious and pathogenic potency of these fungal pathogens, and also provide
insight into potential targets for therapeutic intervention of emmonsiosis and
further research.
PMID- 28409128
TI - The use of bone morphogenetic proteins (BMP) and pseudarthrosis, a literature
review.
AB - Bone morphogenetic proteins (BMP) are multi-functional growth factors to promote
bone healing with the proposal of less morbidity compared to the usual methods of
bone graft harvest. Pseudoarthrosis occur when the fusion attempt fails, a solid
fusion is not achieved, or there is motion across the segment leading to it, and
it can be clinically symptomatic as pain, deformity, neurocompression, or
hardware failure. BMPs are used at spinal fusion as a tool for the treatment of
degenerative, traumatic, neoplastic and infectious conditions of the spine. This
review shows that the use of BMPS is effective and secure when compared with
iliac crest bone graft (ICGB); however, depending of the location of usage
(cervical spine, lumbar spine or sacrum) and the medical status of the patient
(presence of comorbidities, tobacco usage), it is more likely to exhibit
complications. Therefore, the use of these proteins must be an informed decision
of patient and physician preferences.
PMID- 28409129
TI - Malignant transformation in chronic osteomyelitis.
AB - INTRODUCTION: Carcinomatous degeneration is a rare and late complication
developing decades after the diagnosis of chronic osteomyelitis. OBJECTIVES: To
present the results from a retrospective study of six cases of squamous cell
carcinoma arising from chronic osteomyelitis. METHODS: Six cases of chronic
osteomyelitis related to cutaneous squamous cell carcinoma were identified. The
cause and characteristics of the osteomyelitis were analyzed, as well as time up
to malignancy, the suspicion signs for malignancy, the localization and
histological type of the cancer, and the type and result of the treatment.
RESULTS: The mean time between osteomyelitis onset and the diagnosis of malignant
degeneration was 49.17 years (range: 32-65). The carcinoma resulted from tibia
osteomyelitis in five cases and from femur osteomyelitis in one. The pathological
examination indicated cutaneous squamous cell carcinoma in all cases. All the
patients were staged as N0M0, except for one, whose lomboaortic lymph nodes were
affected. The treatment consisted of amputation proximal to the tumor in all
patients. No patient presented signs of local recurrence and only one had
carcinoma metastasis. CONCLUSION: Early diagnosis and proximal amputation are
essential for prognosis and final results in carcinomatous degeneration secondary
to chronic osteomyelitis.
PMID- 28409130
TI - Acute distal biceps ruptures: single incision repair by use of suture anchors.
AB - OBJECTIVE: Clinical and functional assessment of the surgical treatment for acute
injury of the distal insertion of the biceps brachial performed with a surgical
technique using a single incision in proximal forearm and fixation with suture
anchors in the radial tuberosity. METHODS: This study reviewed the medical
records of patients who underwent surgical treatment of distal biceps injury
during the period between January 2008 and July 2014. In a mean follow-up of 12
months, 22 patients with complete and acute injury, diagnosed through physical
examination and imaging studies, were functionally assessed in the postoperative
period regarding the range of motion (degrees of flexion-extension and pronation
supination), the presence of pain (VAS), the Andrews Carson-score, and the Mayo
Elbow Performance Score (MEPS). RESULTS: During the postoperative follow-up
assessment, no patient reported pain by VAS scale; all were satisfied with the
esthetic appearance of the surgery. The range of articular movement remained
unchanged at 95.4% of patients, with the loss of 8 degrees of supination in one
patient. No changes in muscle strength were observed. The results of the Andrews
Carson score were good in 4.6% and excellent in 95.4% of cases; the MEPS
presented 100% of excellent results. The rate of complications was 27.2%, similar
to the literature. CONCLUSION: Surgical repair of acute injury of the distal
biceps trough a single incision in the proximal forearm and fixation with two
suture anchors in the radial tuberosity is an effective and safe therapeutic
option, allowing early motion and good functional results.
PMID- 28409131
TI - Hip disarticulation - case series analysis and literature review.
AB - OBJECTIVE: To present a retrospective study of 16 patients submitted to hip
disarticulation. METHODS: During the period of 16 years, 16 patients who
underwent hip disarticulation were identified. All of them were studied based on
clinical records regarding the gender, age at surgery, disarticulation cause,
postoperative complications, mortality rates and functional status after hip
disarticulation. RESULTS: Hip disarticulation was performed electively in most
cases and urgently in only three cases. The indications had the following
origins: infection (n = 6), tumor (n = 6), trauma (n = 3), and ischemia (n = 2).
The mean post-surgery survival was 200.5 days. The survival rates were 6875%
after six months, 5625% after one year, and 50% after three years. The mortality
rates were higher in disarticulations with traumatic (66.7%) and tumoral (60%)
causes. Regarding the eight patients who survived, half of them ambulate with
crutches and without prosthesis, 25% walk with limb prosthesis, and 25% are
bedridden. Complications and mortality were higher in the cases of urgent
surgery, and in those with traumatic and tumoral causes. CONCLUSION: Hip
disarticulation is a major ablative surgery with obvious implications for limb
functionality, as well as high rates of complications and mortality. However,
when performed at the correct time and with proper indication, this procedure can
be life-saving and can ensure the return to the home environment with a certain
degree of quality of life.
PMID- 28409132
TI - Do patients lose weight after total knee replacement?
AB - OBJECTIVE: Several studies show that patients undergoing total knee arthroplasty
(TKA) tend to maintain or gain weight after the procedure, which would result in
increased wear of the prosthesis and new surgical interventions in a smaller
period of time in comparison with patients with adequate body mass index (BMI).
The aim of this study was to investigate the effect of TKA surgery on these
patients' BMI. METHODS: Initially the records were analyzed, chosen at random
from 91 patients undergoing TKA during the period from August 2011 to July 2013.
Patients were stratified by BMI as normal weight (BMI between 20 and 25),
overweight (BMI between 25 and 30), and obesity (BMI > 30). They were re
evaluated in a minimum period of 18 months. RESULTS: The mean age of the sample
population was 68.1 years; 69.1 for men and 67.2 for women. The mean preoperative
BMI was 27.24 kg/m2. Among the study participants, in the preoperative period, 17
patients had normal weight, 65 were overweight, and nine were obese.
Postoperative analysis showed weight loss in 41 patients (46%), and weight gain
in 50 patients (54%). The mean postoperative BMI was 27.16 kg/m2, in general,
experiencing a slight decline in the mean BMI of 0.08 kg/m2. CONCLUSION: Patients
who underwent TKA did not achieve significant reduction in BMI after surgery.
PMID- 28409133
TI - Evaluation of the functional results after rotator cuff arthroscopic repair with
the suture bridge technique.
AB - OBJECTIVE: To evaluate the results of arthroscopic treatment of large and
extensive rotator cuff injuries (RCI) that involved the supra and infraspinatus
muscles using the suture bridge (SB) technique. METHODS: Between July 2010 and
November 2014, 37 patients with RCI who were treated with SB technique were
evaluated. The study included all patients with a minimum follow-up of 12 months
who underwent primary surgery of the shoulder. Twenty-four patients were male and
13 were female. The mean age was 60 years (45-75). The dominant side was affected
in 32 cases. The most common cause of injury was trauma (18 cases). The mean
preoperative motion was 123 degrees , 58 degrees , T11. Through magnetic
resonance imaging, 36 fatty degenerations were classified according to
Goutallier. Patients underwent rotator cuff repair with SB technique, which
consists of using a medial row anchor with two Corkscrew(r) fibertape(r) or
fiberwire(r) at the articular margin, associated with lateral fixation without
stitch using PushLocks(r) or SwiveLocks(r). RESULTS: The mean age was 60 years
and mean fatty degeneration was 2.6. The mean range of motion (following the
AAOS) in the postoperative evaluation was 148 degrees of forward elevation, 55
degrees in lateral rotation and medial rotation in T9. Using the criteria of the
University of California at Los Angeles (UCLA), 35 (94%) patients had excellent
and good results; one (2.7%), fair; and one (2.7%), poor. CONCLUSION:
Arthroscopic repair of a large and extensive RCI using SB technique had good and
excellent results in 94% of the patients.
PMID- 28409134
TI - Anatomical variations of pronator teres muscle: predispositional role for nerve
entrapment.
AB - OBJECTIVE: To assess the anatomical variations of the pronator teres muscle (PTM)
and its implication in the compression of the median nerve, which passes through
the humeral and ulnar heads of the PTM. METHODS: For the present study, 100 upper
limbs from human cadavers from the anatomy laboratory were dissected. Forty-six
specimens were male and four, female, whose aged ranged from 28 to 77 years; 27
were white and 23, non-white. A pilot study consisting of six hands from three
fresh cadaver dissections was conducted to familiarize the authors with the local
anatomy; these were not included in the present study. RESULTS: The humeral and
ulnar heads of PTM were present in 86 limbs. In 72 out of the 86 limbs, the
median nerve was positioned between the two heads of the PTM; in 11, it passed
through the muscle belly of ulnar head of the PTM, and in three, posteriorly to
both heads of the PTM. When both heads were present, the median nerve was not
observed as passing through the muscle belly of the humeral head of PTM. In 14
out of the 100 dissected limbs, the ulnar head of the PTM was not observed; in
this situation, the median nerve was positioned posteriorly to the humeral head
in 11 limbs, and passed through the humeral head in three. In 17 limbs, the ulnar
head of PTM was little developed, with a fibrous band originating from the ulnar
coronoid process, associated with a distal muscle component near the union with
the humeral head. In four limbs, the ulnar head of the MPR was represented by a
fibrous band. In both limbs of one cadaver, a fibrous band was observed between
the supinator muscle and the humeral head of the PTM, passing over median nerve.
CONCLUSION: The results suggest that these anatomical variations in relationship
median nerve and PTM are potential factors for median nerve compression, as they
narrow the space through which the median nerve passes.
PMID- 28409135
TI - Evaluation of serum levels of C-reactive protein after total knee arthroplasty.
AB - OBJECTIVE: To evaluate the behavior of C-reactive protein (CRP) levels in the
first three weeks after total knee arthroplasty (TKA) and define the factors
related to its variation. METHODS: We evaluated the CRP values in 103 patients
undergoing primary TKA. Serum CRP was measured on the day before surgery, and on
the third and twenty-first days after the procedure. RESULTS: PCR showed sudden
increase on the third day after surgery, reaching the mean value of 111.9 mg/L,
median 75.9 mg/L. Only one-third of the patients returned to normal levels in the
third week. In the immediate postoperative period, CRP was not correlated with
body mass index (BMI), age, gender, blood transfusion, or complications.
CONCLUSION: Serum CRP remains high in the third week after TKA in most patients,
and this change is primarily related to surgical trauma.
PMID- 28409136
TI - Functional outcome after arthroscopic repair of triple shoulder instability.
AB - OBJECTIVE: To evaluate the functional outcomes of patients submitted to
arthroscopic repair of triple labral lesion. METHODS: This was an analytical
retrospective study of patients who underwent arthroscopic treatment of triple
labral lesion from March 2005 to December 2014. Patients with at least one year
of postoperative follow-up were included. A total of nine patients were
evaluated. The mean age was 32.3 years and the dominant side was affected in five
patients. Patients were functionally assessed regarding the range of motion (ROM)
in elevation, external rotation with the arm close to the body the arm in
abduction of 90 degrees , and internal rotation, and by the Carter-Rowe score.
The degree of satisfaction was assessed at the end of the follow-up period.
RESULTS: Three patients had less than five episodes of instability, four patients
had between five and ten episodes, and two patients had more than ten episodes.
Seven patients had positive O'Brien test for SLAP lesions and positive
apprehension test in abduction and external rotation, and only one patient had
apprehension in adduction and internal rotation. Three patients persisted with
positive O'Brien test and one with apprehension in abduction and external
rotation at the end of follow-up. The range of motion was complete in all cases.
The median Carter-Rowe score increased from 40 preoperatively to 90 (p = 0.008).
CONCLUSION: The arthroscopic repair of triple labral lesions allows for the
restoration of the stability of the glenohumeral joint, achieving excellent
functional results.
PMID- 28409137
TI - Posterior three-column osteotomies for the treatment of rigid thoracic kyphosis -
a case series.
AB - OBJECTIVE: To evaluate the results and complications of a series of patients who
underwent three-column osteotomy using the posterior approach for correction of
complex cases of rigid dorsal kyphotic deformity. METHODS: Review of clinical
records and images of 15 consecutive cases of pedicle subtraction osteotomies,
bone-disk-bone osteotomies, or vertebral column resection, recording the
etiology, type and level of osteotomy, extension of fixation, complications, and
pre- and post-surgical measurements of the sagittal curves and pelvic parameters.
RESULTS: Six pedicle subtraction osteotomies were performed, one of which in two
adjacent vertebrae, as well as two bone-disk-bone osteotomies and seven vertebral
column resection, two of which were performed in two adjacent vertebrae. The mean
correction was 39.3 degrees for the angular kyphosis and 33.9 degrees for
dorsal kyphosis. The corrections were similar regardless of the kind of
osteotomy, the operated spinal segment, or the approach in one or two levels, but
this may be a sample effect. Eight complications were observed in six patients
(40% of cases): two medical complications, five early and one late surgical
complication (over 90 days after surgery). There were three reoperations within
less than one year from the initial surgery and one case of persistent
paraparesis. Clinical complications were resolved without sequelae. There was no
significant loss of correction during the segment, except in two cases of major
mechanical failure due to a junctional segment fracture. CONCLUSION: Despite
being complex and aggressive procedures, prone to various complications,
osteotomies with resection of the three columns are highly effective in the
correction of rigid kyphotic deformities and safe enough to justify its use in
selected cases.
PMID- 28409138
TI - Range of motion predictability after total knee arthroplasty with medial pivot
prosthesis.
AB - OBJECTIVE: To assess whether there the final range of motion (ROM) results
achieved by patients undergoing total knee arthroplasty (TKA) with prosthesis
using Medial Pivot design are predictable. METHODS: Between January and August of
2014, 155 patients with primary osteoarthritis of knee who underwent TKA using
the prosthesis ADVANCE(r) Medial Pivot were prospectively assessed. All ROM
measures were made and recorded before, during, and after surgery. All patients
were clinically assessed preoperatively and postoperatively (15, 45 days, three
months, six months, one year, and annually thereafter after surgery); their
functional status was assessed using the WOMAC questionnaire. RESULTS:
Significant differences (p < 0.001) were observed between the means and medians
of ROM in the preoperative when compared with those during the perioperative; the
perioperative values, when compared with those after six months postoperative,
were also different (p < 0.001). No significant differences were found between
the means and medians ROM between the intraoperative period and at the 45-day
assessment (ns) and between the means and medians ROM between the preoperative
period and at the six-month evaluation (ns). CONCLUSION: The final ROM achieved
by patients that underwent TKA with medial pivot prosthesis can be predicted. The
perioperative ROM correlates with that at 45 days after surgery. The final ROM is
correlated with that of the pre-operative period.
PMID- 28409139
TI - Double-bundle PCL reconstruction using autologous hamstring tendons: outcome with
a minimum 2-year follow-up.
AB - OBJECTIVE: To present the outcomes of posterior cruciate ligament (PCL) double
bundle reconstruction using autologous hamstring tendons, with a minimum follow
up of two years. METHODS: Evaluation of 16 cases of PCL injury that underwent
double-bundle reconstruction with autogenous hamstring tendons, between 2011 and
2013. The final sample consisted of 16 patients, 15 men and one woman, with a
mean age of 31 years (21-49). The predominant mechanism was motorcycle accident
in half of the cases. There was a mean interval of 15 months between the time of
lesion and the surgery (three to 52 months). Five lesions were isolated and 11,
associated. Clinical evaluation, application of validated scores, and
measurements with use of the KT-1000 were performed. RESULTS: The analysis showed
a mean preoperative Lysholm score of 50 points (28-87), progressing to 94 points
(85-100) postoperatively. The IKDC score also demonstrated improvement. In the
preoperative evaluation, four and 12 patients were respectively classified as C
(abnormal) and D (very unusual), and in the postoperative evaluation six as A
(normal) and ten as B (close to normal). In the post-operative evaluation by
KT1000 arthrometer, 13 patients showed difference between 0-2 mm and 3 between 3
and 5 mm, when compared with the contralateral side. CONCLUSION: Autologous
hamstring tendons are a viable option in double-bundle reconstruction of the PCL,
with good clinical results in a minimum follow-up of two years.
PMID- 28409140
TI - Osteoid osteoma of the distal clavicle.
AB - The osteoid osteoma is a bone tumor that accounts for 10% of benign tumors. It
was described in 1935 by Jaffe, as a tumor that affects the young adult
population, with a predominance of males. This study aims to present a case of
late diagnosis of a patient with osteoid osteoma of the distal clavicle region.
Female patient, 44 years old, non-professional volleyball player, reported pain
in the anterior and superior region of the shoulder girdle, specifically in the
acromioclavicular joint, which worsened at night and had been treated for nine
months as tendinitis of the rotator cuff and acromioclavicular joint arthritis.
After confirming the diagnosis, the patient underwent open surgery with resection
of the distal clavicle. At two years of follow-up, the patient presents without
local pain. In the radiographic evaluation, coracoclavicular distance is
preserved and there are no signs of recurrence. Tumors of the shoulder girdle are
rare and are often diagnosed late. A high degree of suspicion for the diagnosis
of tumors of the shoulder girdle is needed in order to avoid late diagnosis.
PMID- 28409141
TI - Intrathoracic fracture-dislocation of the humerus - case report and literature
review.
AB - Shoulder fracture-dislocations are uncommon. Those associated with intrathoracic
dislocation are very rare conditions, resulting from high-energy trauma; usually,
the affected limb is in an abduction position. In Brazil, there is only one
report of a teenager with displacement of the epiphysis into the chest cavity;
the present is the first adult patient report of intrathoracic dislocation of the
humerus. The authors present the case of a patient female, aged 56 years, who was
hit by motorcycle and thrown approximately 5 meters away. She was rescued on site
with thoracic, pelvic, and right upper limb trauma. Her chest was drained due to
pneumothorax and multiple fractures of ribs; she was diagnosed with fracture
dislocation in four parts, with intrathoracic dislocation of the humeral head.
Displaced forearm bones fracture was also diagnosed; the olecranon, scaphoid, and
ischiopubic fractures were not displaced. The patient underwent a joint procedure
with a cardiothoracic surgery team to remove the humeral head through thoracotomy
and chest drainage; subsequently, a partial arthroplasty of the humerus was
performed, with graft from the humeral head and fixation of forearm fractures.
Conservative treatment was chosen for the other fractures. After three months,
all fractures were healed with gradual functional improvement. The patient
remained in physiotherapy and orthopedic monitoring, having been discharged from
the thoracic surgery; in a severe depressive episode, the patient committed
suicide after 11 months of the trauma.
PMID- 28409142
TI - Snapping scapula. Arthroscopic resection of osteochondroma of the subscapularis
superomedial angle. Case report and literature review.
AB - Snapping scapula syndrome has several etiologies, including subscapular
osteochondroma. When this tumor needs to be removed, this can be done
arthroscopically, a procedure that has restricted indications. The authors
present a case of a patient with superomedial subscapular osteochondroma who
underwent a scapulothoracic arthroscopy for its removal.
PMID- 28409143
TI - Giant Schwannoma of ulnar nerve: case report.
AB - Schwannomas are the most common benign neoplasms of the peripheral nerves in the
upper limbs. Although many are asymptomatic, they can produce a mass effect, thus
impinging against soft tissues or interfering with joint function. The authors
present a case report and a review of a giant Schwannoma in the ulnar nerve.
PMID- 28409144
TI - Hemarthrosis subtalar, a rare diagnosis.
AB - Type B hemophilia usually affects patients with a family history of this disease
and has a typical clinical picture. However, in the present case it appeared in a
patient outside the typical age with no family history of hematologic
malignancies and with an unusual clinical picture.
PMID- 28409145
TI - Extra-articular and transcutaneous migration of the poly-l/d-lactide interference
screw after popliteal tendon reconstruction.
AB - Knee ligament reconstructions are commonly performed orthopedic procedures. Graft
fixation is generally performed with metallic or absorbable interference screws.
In a recent study, only ten reports of screw migration were retrieved; of these,
only one was not related to the anterior cruciate ligament, and the majority was
related to the use of poly-l-lactic acid (PLLA) screws. Only one case retrieved
in the literature reported screw migration in reconstructions of the
posterolateral corner, and that was to the intra-articular region. In the present
article, the authors report a case of extra-articular and transcutaneous
migration of a poly-l/d-lactide (PDLLA) interference screw following popliteal
tendon reconstruction. Besides being the first case of popliteal tendon migration
with extra-articular screw migration, no reports of PDLLA screw migration were
retrieved in the literature.
PMID- 28409146
TI - Pindborg tumor in the distal femur.
AB - To describe a case of possible diagnosis of Pindborg tumor on the distal femur. A
32-years-old female patient, a native of Bolivia, resident in Brazil, arrived to
this service for tumor research in the right femur. After biopsies and resection
of the lesion, the case was referred to analysis and consultancy in the United
States. In a report of review by the Pathology Laboratory, it was characterized
the histological appearance and immunohistochemical profile were characteristic
of Pindborg tumor. Currently, the patient is being followed-up at the Orthopedics
and Traumatology Department of this institution, and presents a good evolution.
This study presents the case of a patient with a rare tumor that was investigated
for an extensive period and through many tests. Pindborg tumor was suggested as a
diagnostic hypothesis due to the characteristics and behavior of the neoplastic
lesion. Although this lesion is more commonly observed in odontology, the
neoplasia was compatible with the diagnosis. Therefore, despite the fact that
this tumor has benign characteristics, long-term monitoring is necessary, given
the high rate of tumor recurrence.
PMID- 28409147
TI - Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum
Biomarker in Liver Transplant Recipients.
AB - Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the
liver transplant (LT) population. We employed a simple serum biomarker to
elucidate incidence and predictors of advanced fibrosis after LT over a long
follow-up period. Methods. We included 440 consecutive patients who underwent LT
between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond
12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189
(43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95%
confidence interval [CI], 8.1-10.7). Advanced fibrosis was predicted by chronic
HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92-5.36, p < 0.001),
hypoalbuminemia (aHR = 2.31, 95% CI 1.72-3.09; p < 0.001), and hyponatremia (aHR
= 1.48, 95% CI 1.09-2.01; p = 0.01). LT recipients with more than 1 predictor had
a higher incidence of advanced fibrosis, the highest being when all 3 predictors
coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection,
hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis
following LT. Patients with these risk factors should be serially monitored using
noninvasive fibrosis biomarkers and prioritized for interventions.
PMID- 28409148
TI - Position Paper of INoEA Working Group on Long-Gap Esophageal Atresia: For Better
Care.
AB - INoEA is the International Network of Esophageal Atresia and consists of a broad
spectrum of pediatric specialties and patient societies. The working group on
long-gap esophageal atresia (LGEA) set out to develop guidelines regarding the
definition of LGEA, the best diagnostic and treatment strategies, and highlight
the necessity of experience and communication in the management of these
challenging patients. Review of the literature and expert discussion concluded
that LGEA should be defined as any esophageal atresia (EA) that has no intra
abdominal air, realizing that this defines EA with no distal tracheoesophageal
fistula (TEF). LGEA is considerably more complex than EA with distal TEFs and
should be referred to a center of expertise. The first choice is to preserve the
native esophagus and pursue primary repair, delayed primary anastomosis, or
traction/growth techniques to achieve anastomosis. A cervical esophagostomy
should be avoided if possible. Only if primary anastomosis is not possible,
replacement techniques should be used. Jejunal interposition is proposed as the
best option among the major EA centers. In light of the infrequent occurrence of
LGEA and the technically demanding techniques involved to achieve esophageal
continuity, it is strongly advised to develop regional or national centers of
expertise for the management and follow-up of these very complex patients.
PMID- 28409149
TI - Collaborative Implementation Strategy for Newborn Resuscitation and Essential
Care Training in the Dominican Republic.
AB - BACKGROUND: Neonatal mortality accounts for 45% of under-5 mortality worldwide,
with 98% of newborn deaths occurring in developing countries. The Dominican
Republic (DR) demonstrates one of the highest neonatal mortality rates in Latin
America despite broad access to care. Strategies to support professional capacity
building and strengthen the local health care system are needed to improve
neonatal outcomes in the DR. RATIONALE: Helping babies breathe (HBB) and
essential care for every baby (ECEB) are evidence-based newborn resuscitation and
essential care training programs that have been shown to improve providers'
confidence, knowledge, and clinical skills. Lack of professional support and
infrequent resuscitation skills practice are commonly cited as barriers to skill
retention after HBB training, while establishment of program mentoring and
regular skills refreshers are associated with retention of clinical knowledge and
skills and improved clinical performance and outcomes. Global partnerships to
facilitate implementation of a comprehensive newborn resuscitation and essential
care training program with ongoing clinical and program mentorship in the DR
should have a lasting impact on workforce capacity, quality of care, and clinical
outcomes. METHODS: A multidisciplinary, international group of clinicians
partnered with the Ministry of Health to design and implement a comprehensive
newborn health initiative in the DR. A train-the-trainer model structured the
regional rollout of a combined HBB/ECEB program with integrated quality
improvement (QI) initiatives and systems for ongoing program monitoring,
reinforcement, and mentorship. Cognitive, affective, behavioral, and clinical
outcomes are being measured. RESULTS: Seventeen local champions representing six
hospitals participated in the HBB/ECEB master trainer course and design of a QI
tool for site-specific clinical performance monitoring. One hundred seventy-eight
and 171 providers participated in HBB and ECEB courses, respectively, at pilot
sites during the following year. Participants completed prior training need
assessment, pre-/post-knowledge assessments and course evaluations. Program
mentorship and monitoring of continuing education and clinical performance are
ongoing. The Ministry of Health has assumed responsibility for program
sustainability and current scale-up, including integration of maternal
resuscitation training. CONCLUSION: International partnerships facilitated the
collaborative implementation of scalable, locally sustainable newborn
resuscitation and essential care training in the DR, mobilizing local resources
and empowering the workforce to capably pursue improved care of an exceedingly
vulnerable community.
PMID- 28409150
TI - Mitotic Catastrophe in BC3H1 Cells following Yessotoxin Exposure.
AB - The marine toxin yessotoxin (YTX) can cause various cytotoxic effects depending
on cell type and cell line. It is well known to trigger distinct mechanisms for
programmed cell death which may overlap or cross-talk. The present contribution
provides the first evidence that YTX can cause genotoxicity and induce mitotic
catastrophe which can lead to different types of cell death. This work also
demonstrates potential information gain from non-intrusive computer-based
tracking of many individual cells during long time. Treatment of BC3H1 cells at
their exponential growth phase causes atypical nuclear alterations and formation
of giant cells with multiple nuclei. These are the most prominent morphological
features of mitotic catastrophe. Giant cells undergo slow cell death in a
necrosis-like manner. However, apoptotic-like cell death is also observed in
these cells. Electron microscopy of treated BC3H1 cells reveal uncondensed
chromatin and cells with double nuclei. Activation of p-p53, p-H2AX, p-Chk1, p
ATM, and p-ATR and down-regulation of p-Chk2 indicate DNA damage response and
cell cycle deregulation. Micronuclei formation further support this evidence.
Data from tracking single cells reveal that YTX treatment suppresses a second
round of cell division in BC3H1 cells. These findings suggest that YTX can induce
genomic alterations or imperfections in chromosomal segregation leading to
permanent mitotic failure. This understanding extends the list of effects from
YTX and which are of interest to control cancer and tumor progression.
PMID- 28409151
TI - Temporal Changes in Gene Expression Profile during Mature Adipocyte
Dedifferentiation.
AB - Objective. To characterize changes in gene expression profile during human mature
adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and
omental (OM) adipose tissue samples were obtained from 4 participants paired for
age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene
expression analysis at days 0, 4, 7, and 12 of the cultures was performed using
Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to
similarity of expression changes was used to identify overrepresented functions.
Results. Four clusters gathered genes with similar expression between day 4 to
day 7 but decreasing expression from day 7 to day 12. Most of these genes coded
for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ,
CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for
proteins implicated in cellular proliferation and growth or cell cycle increased
significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for
extracellular matrix proteins were differentially expressed between days 0, 4, 7,
and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion.
Dedifferentiation is associated with downregulation of transcripts encoding
proteins involved in mature adipocyte functions and upregulation of genes
involved in matrix remodeling, cellular development, and cell cycle.
PMID- 28409153
TI - Joint Covariate Detection on Expression Profiles for Selecting Prognostic miRNAs
in Glioblastoma.
AB - An important application of expression profiles is to stratify patients into high
risk and low-risk groups using limited but key covariates associated with
survival outcomes. Prior to that, variables considered to be associated with
survival outcomes are selected. A combination of single variables, each of which
is significantly related to survival outcomes, is always regarded to be
candidates for posterior patient stratification. Instead of individually
significant variables, a combination that contains not only significant but also
insignificant variables is supposed to be concentrated on. By means of bottom-up
enumeration on each pair of variables, we propose a joint covariate detection
strategy to select candidates that not only correspond to close association with
survival outcomes but also help to make a clear stratification of patients.
Experimental results on a publicly available dataset of glioblastoma multiforme
indicate that the selected pair composed of an individually significant and an
insignificant miRNA keeps a better performance than the combination of
significant single variables. The selected miRNA pair is ultimately regarded to
be associated with the prognosis of glioblastoma multiforme by further pathway
analysis.
PMID- 28409152
TI - The Association between Imaging Parameters of the Paraspinal Muscles, Spinal
Degeneration, and Low Back Pain.
AB - This narrative review investigated imaging parameters of the paraspinal muscles
and their association with spinal degenerative features and low back pain (LBP)
found in the literature. Three principal signs of muscle degeneration were
detected on imaging: decreased muscle size, decreased radiographic density, and
increased fat deposits. Men have a higher density of paraspinal muscles than
women, younger individuals have a higher density than older ones, and lean
individuals have a higher density than those with an increased body mass index.
Fatty infiltration appears to be a late stage of muscular degeneration and can be
measured noninvasively by an MRI scan. Fatty infiltration in the lumbar
multifidus is common in adults and is strongly associated with LBP, especially in
women, independent of body composition. Fatty infiltration develops in areas
where most degenerative changes are found. MR spectroscopy studies have
corroborated that the lumbar multifidus in LBP subjects has a significantly
higher fat content than asymptomatic controls. There is a strong need for
establishing uniform methods of evaluating normal parameters and degenerative
changes of the paraspinal muscles. Additional imaging studies are needed to
improve the understanding of the association and causal relationships between
LBP, spinal degeneration, and changes in the paraspinal muscles.
PMID- 28409154
TI - Suspected Fetal Growth Restriction at 37 Weeks: A Comparison of Doppler and
Placental Pathology.
AB - Objective. Our objective was determining if abnormal Doppler evaluation had a
higher prevalence of placental pathology compared to normal Doppler in suspected
fetal growth restriction (FGR) of cases delivered at 37 weeks. Study Design. This
retrospective cohort study of suspected FGR singletons with antenatal Doppler
evaluation delivered at 37 weeks had a primary outcome of the prevalence of
placental pathology related to FGR. Significance was defined as p <= 0.05.
Results. Of 100 pregnancies 46 and 54 were in the abnormal and normal Doppler
cohorts, respectively. Placental pathology was more prevalent with any abnormal
Doppler, 84.8% versus 55.6%, odds ratio (OR) 4.46, 95% confidence interval (CI):
1.55, 13.22, and p = 0.002. Abnormal middle cerebral artery (MCA) Doppler had a
higher prevalence: 96.2% versus 54.8%, OR 20.7, 95% CI: 2.54, 447.1, and p <
0.001. Conclusion. Abnormal Doppler was associated with more placental pathology
in comparison to normal Doppler in fetuses with suspected FGR. Abnormal MCA
Doppler had the strongest association.
PMID- 28409155
TI - Preservation of Myocardial Perfusion and Function by Keeping Hypertrophied Heart
Empty and Beating for Valve Surgery: An In Vivo MR Study of Pig Hearts.
AB - Objectives. Normothermic hyperkalemic cardioplegia arrest (NHCA) may not
effectively preserve hypertrophied myocardium during open-heart surgery.
Normothermic normokalemic beating perfusion (NNBP), keeping hearts empty-beating,
was utilized as an alternative to evaluate its cardioprotective role. Materials
and Methods. Twelve hypertrophied pig hearts at 58.6 +/- 7.2 days after ascending
aorta banding underwent NNBP and NHCA, respectively. Near infrared myocardial
perfusion imaging with indocyanine green (ICG) was conducted to assess myocardial
perfusion. Left ventricular (LV) contractile function was assessed by cine MRI.
TUNEL staining and western blotting for caspase-3 cleavage and cardiac troponin I
(cTnI) degradation were conducted in LV tissue samples. Results. Ascending aortic
diameter was reduced by 52.7% +/- 0.4% at approximately fifty-eight days after
banding. LV wall thickness was significantly higher in aorta banding than in sham
operation. Myocardial blood flow reflected by maximum ICG absorbance value was
markedly higher in NNBP than in NHCA. The amount of apoptotic cardiomyocyte was
significantly lower in NNBP than in NHCA. NNBP alleviated caspase-3 cleavage and
cTnI degradation associated with NHCA. NNBP displayed a substantially increased
postoperative ejection fraction relative to NHCA. Conclusions. NNBP was better
than NHCA in enhancing myocardial perfusion, inhibiting cardiomyocyte apoptosis,
and preserving LV contractile function for hypertrophied hearts.
PMID- 28409156
TI - Curcumin Analogue CA15 Exhibits Anticancer Effects on HEp-2 Cells via Targeting
NF-kappaB.
AB - Laryngeal carcinoma remains one of the most common malignancies, and curcumin has
been proven to be effective against head and neck cancers in vitro. However, it
has not yet been applied in clinical settings due to its low stability. In the
current study, we synthesized 34 monocarbonyl analogues of curcumin with stable
structures. CA15, which exhibited a stronger inhibited effect on laryngeal cancer
cells HEp-2 but a lower toxicity on hepatic cells HL-7702 in MTT assay, was
selected for further analysis. The effects of CA15 on cell viability,
proliferation, migration, apoptosis, and NF-kappaB activation were measured using
MTT, Transwell migration, flow cytometry, Western blot, and immunofluorescence
assays in HEp-2 cells. An NF-kappaB inhibitor, BMS-345541, as well as curcumin
was also tested. Results showed that CA15 induced decreased toxicity towards HL
7702 cells compared to curcumin and BMS-345541. However, similar to BMS-345541
and curcumin, CA15 not only significantly inhibited proliferation and migration
and induced caspase-3-dependent apoptosis but also attenuated TNF-alpha-induced
NF-kappaB activation in HEp-2 cells. These results demonstrated that curcumin
analogue CA15 exhibited anticancer effects on laryngeal cancer cells via
targeting of NF-kappaB.
PMID- 28409157
TI - Ferulic Acid Suppresses Amyloid beta Production in the Human Lens Epithelial Cell
Stimulated with Hydrogen Peroxide.
AB - It is well known that oxidative stresses induce the production of amyloid beta
(Abeta) in the brain, lens, and retina, leading to age-related diseases. In the
present study, we investigated the effects of ferulic acid on the Abeta levels in
H2O2-stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of Abeta
peptides (Abeta1-40, Abeta1-42, and Abeta1-43) were measured by ELISA, and the
levels of mRNA for the expressed proteins related to Abeta production (APP,
BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were
determined by quantitative real-time RT-PCR. H2O2 stimulation augmented gene
expression of the proteins related to Abeta production, resulting in the
production of three types of Abeta peptides. Treatment with 0.1 MUM ferulic acid
attenuated the augmentations of gene expression and production of the proteins
related to the secretion of three types of Abeta peptides in the H2O2-stimulated
HLE cells. These results provided evidence of antioxidative functions of ferulic
acid for lens epithelial cells.
PMID- 28409158
TI - Metformin Use Is Associated with Reduced Incidence and Improved Survival of
Endometrial Cancer: A Meta-Analysis.
AB - Studies have suggested that metformin can potentially decrease the incidence of
cancer and improve survival outcomes. However, the association between metformin
use and the incidence and survival of endometrial cancer (EC) remains
controversial. So, a meta-analysis was performed. An electronic search was
conducted using PubMed, EMBASE, and Web of Science. The outcome measures were
relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs)
comparing the EC incidence and survival in patients treated with and without
metformin. Eleven studies involving 766,926 participants were included in this
study. In the pooled analysis of five studies which evaluated the association of
metformin use with the incidence of EC, we found that metformin use was
associated with a 13% reduction in EC risk among patients with diabetes (RR =
0.87, 95% CI: 0.80-0.95; p = 0.006). In the pooled analysis of six retrospective
cohort studies evaluating the effect of metformin on the survival of EC patients,
we found that, relative to nonuse, metformin use significantly improved the
survival of EC patients (HR = 0.63, 95% CI: 0.45-0.87; p = 0.006). This study
showed that metformin use was significantly associated with a decreased incidence
of EC in diabetes and a favorable survival outcome of EC patients.
PMID- 28409159
TI - Nutritional Composition and Phytochemical, Antioxidative, and Antifungal
Activities of Pergularia tomentosa L.
AB - Crude extracts from a medicinal Tunisian plant, Pergularia tomentosa L., were the
investigated natural material. Butanolic extract of roots analyzed with IR
spectra revealed the presence of hydroxyl, alcoholic, and carboxylic groups and
sugars units. Analysis of some secondary metabolites, total phenolic, flavonoids,
flavonols, and procyanidins, was performed using different solvents following the
increased gradient of polarity. Fruits and leaves contained the highest amounts
of all these compounds. Antioxidant properties were evaluated by the
determination of free radical scavenging activity and the reducing power of
methanolic extracts. Fruits and leaf extracts were the most powerful antioxidants
for the two-assay in vitro system. Stems and fruits extracts exhibit an
antifungal activity against Fusarium oxysporum f. sp. lycopersici which could
become an alternative to synthetic fungicide to control Solanum species fungal
diseases.
PMID- 28409161
TI - Corrigendum to "Brain Activation and Psychomotor Speed in Middle-Aged Patients
with Type 1 Diabetes: Relationships with Hyperglycemia and Brain Small Vessel
Disease".
AB - [This corrects the article DOI: 10.1155/2016/9571464.].
PMID- 28409160
TI - Peripheral and Autonomic Neuropathy in South Asians and White Caucasians with
Type 2 Diabetes Mellitus: Possible Explanations for Epidemiological Differences.
AB - Objectives. To compare the prevalence of diabetic peripheral neuropathy (DPN) and
that of cardiac autonomic neuropathy (CAN) between South Asians and White
Caucasians with type 2 diabetes and to explore reasons for observed differences.
Methods. A cross-sectional study of casually selected South Asian and White
Caucasian adults attending a hospital-based diabetes clinic in the UK. DPN and
CAN were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and
heart rate variability testing, respectively. Results. Patients (n = 266) were
recruited (47.4% South Asians). DPN was more common in White Caucasians compared
to South Asians (54.3% versus 38.1%, p = 0.008). Foot insensitivity as assessed
by 10 g monofilament perception was more common in White Caucasians (43.9% versus
23.8%, p = 0.001). After adjustment for confounders, White Caucasians remained
twice as likely to have DPN as South Asians, but the impact of ethnicity became
nonsignificant after adjusting for adiposity measures or height. No difference in
prevalence of standardized CAN test abnormalities was detected between
ethnicities. Skin microvascular assessment demonstrated that South Asians had
reduced heating flux but preserved acetylcholine response. Conclusions. South
Asians with type 2 diabetes have fewer clinical signs of DPN compared to White
Caucasians. Differences in adiposity (and its distribution) and height appear to
explain these differences.
PMID- 28409162
TI - Synergistic Effect of the MTHFR C677T and EPHX2 G860A Polymorphism on the
Increased Risk of Ischemic Stroke in Chinese Type 2 Diabetic Patients.
AB - The aim of this study was to investigate the relationship between the combined
effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and
ischemic stroke in Chinese T2DM patients. This case-control study included a
total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and
390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were
genotyped using real-time polymerase chain reaction. Statistical analysis was
performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and
EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with
the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR =
3.46 and OR = 3.42, resp.; P = .001 and P = .002, resp.). The A allele showed
marked association with a lower risk of ischemic stroke in patients with the
lowest Hcy levels under additive, recessive, and dominant genetic models (OR =
0.45, OR = 0.11, and OR = 0.44, resp.; P = .002, P = .035, and P = .008, resp.),
which was not observed in medium or high Hcy level groups. In conclusion, the T
allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic
stroke in the Chinese T2DM population.
PMID- 28409164
TI - Health Related Quality of Life in Iranian Elderly Citizens: A Systematic Review
and Meta-Analysis.
AB - BACKGROUND: The ever-growing elderly population of Iran and their physical and
mental consequences put emphasis on the necessity of determining the quality of
life (QoL) in this social group. This systematic review and meta-analysis aimed
to estimate the mean score of QoL in Iranian elderly citizens. METHODS: Twenty
one articles that were indexed in Iranian (MagIran and Iran Medex) and
international (Scientific Information Database, Google Scholars, Science Direct,
PubMed, ProQuest, Scopus) databases were selected. The articles have used the
Short Form Health Survey (SF-36) to measure QoL in Iranian elderly. The collected
data were analyzed using a random effects model, while heterogeneity of the
studies was measured by I2 index. The data analysis was performed by STATA.
RESULTS: The sample size of the 21 articles was 5318 and the mean score of QoL in
the healthy and sick elderly citizens was 53.8 (CI 95%: 49.4-58.2) and 50.6 (CI
95%: 38.4-62.9) respectively. In addition, there was no significant relationship
between the score of QoL and the year of publication of the articles. (P=0.748).
CONCLUSION: Given that QoL of the studied elderly was almost at an average level,
there is a need to codify and implement comprehensive programs through effective
training programs toward improving QoL of the elderly.
PMID- 28409163
TI - PGC1alpha Activators Mitigate Diabetic Tubulopathy by Improving Mitochondrial
Dynamics and Quality Control.
AB - Purpose. In this study, we investigated the effect of PGC1alpha activators on
mitochondrial fusion, fission, and autophagic quality control in renal tubular
cells in a diabetic environment in vivo and in vitro. We also examined whether
the upregulation of PGC1alpha attenuates diabetic tubulopathy by normalizing
mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose
conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50
mg/kg i.p. for 5 days) in male C57/BL6J mice. AICAR or metformin was used as a
PGC1alpha activator. Results. Treatment with the PGC1alpha activators AICAR and
metformin improved functional mitochondrial mass in HKC8 cells in high-glucose
conditions. Moreover, in renal proximal tubular cells, increased PGC1alpha
activity correlated with the reversal of changes in Drp1, Mfn1, and LC3-II
protein expression in a high-glucose environment. Normalized mitochondrial life
cycles resulted in low ROS production and reduced apoptosis. AICAR and metformin
treatment effectively mitigated albuminuria and renal histopathology and
decreased the expression of TGFbeta1 and alphaSMA in the kidneys of diabetic
mice. Conclusions. Our results demonstrate that increases in PGC1alpha activity
improve diabetic tubulopathy by modulating mitochondrial dynamics and autophagy.
PMID- 28409165
TI - Effects of Collaboration Care Model on the Quality of Life in Patients after
Coronary Angioplasty: A Randomized Controlled Clinical Trial.
AB - BACKGROUND: Coronary artery diseases and therapies such as coronary angioplasty
would lead to changes in the quality of life in patients. The aim of this study
was to determine the effects of collaborative care model on the quality of life
in patients after coronary angioplasty. METHODS: This randomized controlled
clinical trial was conducted in Isfahan, Iran during 2015. In this study, 50
samples were selected by simple sampling and randomly allocated into two equal
groups of intervention and control. Collaborative care model was performed in the
intervention group for 3 months. Data were collected using quality of life (SF
36) questionnaire which includes 36 questions on physical and psychological
dimensions and was completed before and one month after the intervention in both
groups. Data were analyzed using descriptive and analytical statistics and by
independent t- test, paired t test, Chi square and Mann-Whitney tests through
SPSS 18. RESULTS: After the intervention, the mean score of quality of life in
the intervention group was significantly higher than the control group (P<0.05).
The results of independent t-test showed a significant difference between both
groups regarding the mean of changes in the score of quality of life and its
dimensions in patients undergoing coronary angioplasty 3 months after the
intervention (P<0.001). CONCLUSION: Results revealed that patients who had been
cared based on collaborative care model had better scores of quality of life in
all the physical, mental and social dimensions than the control group. Therefore,
using this model for taking care of patients after coronary angioplasty is
recommended. Trial Registration Number: IRCT2015120120912N4.
PMID- 28409166
TI - The Relationship of Socio-Demographic Factors, Fertility Behavior and Child's
Perceived Value with Fertility.
AB - BACKGROUND: Fertility intention is one of the strongest predictors of couple's
fertility behavior that is affected by many variables. This study aimed to
identify the relationship of socio-demographic factors, fertility behavior, and
child's perceived value with fertility intention of women in a region in the east
Iran. METHODS: In this descriptive cross-sectional study, 241 married women aged
between 15 and 49 years of Torbat Heydariyeh City in 2015, were studied. The data
collection scales included a demographic information form, fertility information
questionnaire and Trommsdorff's child value questionnaire. Data were analyzed
using SPSS 16 by Chi-square, Kruskal-Wallis, t-independent test and logistic
regression. The significance level of P<0.05 was considered. RESULTS: Most of the
subjects (52.7%) had no fertility intention. Independent-samples test and Kruskal
Wallis revealed significant differences in fertility intention with the subject's
age, mate's age, number of children and costs of children (P=0.001). In addition,
in subjects with children of both sexes, intention for childbearing was
significantly lower when compared to subjects with only one sex in children
(P=0.001). However, when the logistic regression test was performed, being
housewife, number of children, having children of both sexes, benefit and costs
of children showed statistical significance (P<0.05). CONCLUSION: The results
indicate that being housewife, number of current children, having children of
both sexes, and perceived childbearing costs are important in determining the
odds that a woman will intend to have a child. These findings can contribute to
the realization of new population programs towards higher fertility rate in the
country.
PMID- 28409167
TI - Changes in Daily Life of Iranian Patients with implantable Cardioverter
Defibrillator: A Qualitative Study.
AB - BACKGROUND: Although Implantable Cardioverter Defibrillator (ICD) saves the life
of patients with life-threatening ventricular dysrhythmias, it causes various
challenges in their life span. Considering the increase in the number of ICD
users, more knowledge is required regarding changes in the patients' life after
device implantation. The aim of this study was description of changes in daily
life of patients after ICD implantation. METHODS: This qualitative study was
conducted through content analysis method. The participants were selected through
purposive sampling. They included 3 women and 9 men whose ages ranged from 24 to
74 years, with the mean age of 42.58+1.55 years. They had implanted ICDs in order
to treat life-threatening dysrhythmias. The study data were collected through
interview and field notes from November 2013 to October 2014. The data were
simultaneously analyzed using constant comparative analysis. RESULTS: Through
analysis of the study data, 2 categories were emerged representing dimensions of
changes in daily life of the patients with ICD. These categories were changes in
the social role and familial challenges after implantation. Change in social role
included the following subcategories: "Change in manifestation of routines",
"Shift in leisure time", "Change in job and education status", and "Change in
interaction between the patient and society members". In addition, familial
challenges after implantation consisted of 2 subcategories, namely "Difficulty in
marriage" and "ICD implantation and a range of familial changes". CONCLUSION: The
study findings can be of great importance in nurses' clinical practice for
providing the patients with holistic care, education, support, and follow-up.
They can also be used as a guide assisting clinical treatment of the patients
with ICD.
PMID- 28409168
TI - A Comparative Study of Mindfulness Efficiency Based on Islamic-Spiritual Schemes
and Group Cognitive Behavioral Therapy on Reduction of Anxiety and Depression in
Pregnant Women.
AB - BACKGROUND: Anxiety and depression during the pregnancy period are among the
factors affecting the pregnancy undesirable outcomes and delivery. One way of
controlling anxiety and depression is mindfulness and cognitive behavioral
therapy. The purpose of this study was to compare the efficiency of mindfulness
based on the Islamic-spiritual schemas and group cognitive behavioral therapy on
reduction of anxiety and depression in pregnant women. METHODS: The research
design was semi-experimental in the form of pretest-posttest using a control
group. Among the pregnant women in the 16th to 32nd weeks of pregnancy who
referred to the health center, 30 pregnant women with high anxiety level and 30
pregnant women with high depression participated in the research. Randomly 15
participants with high depression and 15 participants with high anxiety were
considered in the intervention group under the treatment of mindfulness based on
Islamic-spiritual schemes. In addition, 15 participants with high scores
regarding depression and 15 with high scores in anxiety were considered in the
other group. .The control group consisted of 15 pregnant women with high anxiety
and depression. Beck anxiety-depression questionnaire was used in two steps of
pre-test and post-test. Data were analyzed using SPSS, version 20, and P<=0.05
was considered as significant. RESULTS: The results of multivariate analysis of
variance test and tracking Tokey test showed that there was a significant
difference between the mean scores of anxiety and depression in the two groups of
mindfulness based on spiritual- Islamic scheme (P<0.001) and the group of
cognitive behavioral therapy with each other (P<0.001) and with the control
group(P<0.001). The mean of anxiety and depression scores decreased in the
intervention group, but it increased in the control group. CONCLUSION: Both
therapy methods were effective in reduction of anxiety and depression of pregnant
women, but the effect of mindfulness based on spiritual- Islamic schemes was
more.
PMID- 28409169
TI - The Effectiveness of a Peer Coaching Education on Control and Management of Type
2 Diabetes in Women: A Protocol for a Randomized Controlled Trial.
AB - BACKGROUND: Diabetes Education by Peer Coaching is a strategy which helps the
patients with diabetes in the field of behavioral and emotional problems.
However, the results of studies in this field in other countries could not be
generalized in our context. So, the current study aimed to examine the
effectiveness of Diabetes Education by Peer Coaching on Diabetes Management.
METHODS: Outcome variables for patients and peer coaches are measured at baseline
and in3,6 and 12 months. The primary outcome consisted of Fasting Blood Sugar
(FBS) and HbA1c. Secondary outcomes included Blood Pressure (BP), Body Mass Index
(BMI,) Waist-Hip Ratio (WHR), Lipid Profile, diabetes self-care activities,
diabetes-related quality of life, depression, and Social Capital levels.Initial
analyses compared the frequency of baseline levels of outcome and other variables
using a simple Chi-square test, t-test and the Mann-Whitney- U test. Sequential
measurements in each group were evaluated by two-way analysis of variance. If
significant differences in baseline characteristics were found, analyses were
repeated adjusting for these differences using ANOVA and logistic regression for
multivariate analyses. Additional analyses were conducted to look for the
evidence of effect modification by pre-specified subgroups. CONCLUSION: The fact
is that self-control and self-efficacy in diabetes management and treatment of
diabetes could be important components. It seems that this research in this
special setting with cultural differences would provide more evidence about peer
coaching model. It seems that if the peer-coaching model improves learning
situations between patients with diabetes by offering one-on-one Diabetes Self
Management Education, it could be an interactive approach to diabetic education.
Trial Registration Number: IRCT201501128175N3.
PMID- 28409170
TI - The Effect of Pender's Health Promotion Model in Improving the Nutritional
Behavior of Overweight and Obese Women.
AB - BACKGROUND: Changes in lifestyle and eating habits have put women at risk of
obesity and overweight more than ever. This aim of this study was to investigate
the effect of Pender's Health Promotion Model (HPM) to improve the nutritional
behavior of overweight and obese women admitted to Fatemiyeh Hospital clinics in
Hamadan, west Iran in 2015. METHODS: In this quasi-experimental study, 108
eligible women were selected and randomly assigned to two groups: one
experimental and one control. Data were gathered using three questionnaires:
demographics, Pender's HPM constructs, and nutritional behavior. The
questionnaires were filled out by both groups as pre-test and two months later. A
Pender's HPM-based intervention was conducted for the experimental group. The
data were analyzed by paired and independent t-tests, ANCOVA, and Spearmans'
correlation coefficient in SPSS/16. The level of significance was considered to
be <0.05. RESULTS: The mean score of nutritional behavior was 41.75+/-3.28 and
42.36+/-3.69 before the intervention and 79.09+/-5.27 and 49.72+/-9.49 after it
in the experimental and control groups, respectively. The difference was
significant only between before and after the intervention in the experimental
group (P<0.001). Furthermore, the mean scores of the following variables were
significantly different between before and after the intervention in the
experimental group: nutritional behavior, perceived benefits, perceived self
efficacy, commitment to action, interpersonal and situational influences,
behavior-related affect, and perceived barriers (P<0.001). CONCLUSION: The
results showed that Pender's HPM-based training improved nutritional behavior and
some constructs of the model. Therefore, this educative model can be used by
healthcare providers to improve the nutritional and other health promoting
behaviors.
PMID- 28409171
TI - Determinants of Social Accountability in Iranian Nursing and Midwifery Schools: A
Delphi Study.
AB - BACKGROUND: Revising the medical education programs to meet the needs of society
has become both a necessity and an important priority due to the considerable
increase of population, changing patterns of diseases, and new health priorities.
While this necessity has been highlighted in Iran's Fifth Development Plan as
well as its National 2025 Vision Plan, the determinants of social accountability
have not been explained yet. This study aimed to develop determinants of social
accountability in the Iranian Nursing and Midwifery Schools. METHODS: This
classic Delphi study included thirty experts in Nursing and Midwifery Education,
Research and Services selected based on purposive sampling and three rounds of
Delphi technique and conducted in Nursing and Midwifery School of Mashhad
University of Medical Sciences. The primary data were collected using an initial
structured questionnaire prepared through extensive review of literature. SPSS
11.5 software was used to analyze the data. The interquartile deviation and
percentage of agreement were also used to study the consensus of opinion by
experts. RESULTS: Finding obtained from the rounds of Delphi resulted in
selecting 69 determinants out of the initial pool of 128 primary determinants of
social accountability. The items were selected based on experts' consensus and
categorized under three main activities of Nursing and Midwifery School, namely
education, research, and service. CONCLUSION: Social accountability determinants
were explained by 69 items for Schools of Nursing and Midwifery in Iran. The
proposed determinants can be used by managers and authorities of Nursing and
Midwifery School, policy makers, and evaluating institutions associated with them
to ensure realizing social accountability goals.
PMID- 28409172
TI - Knowledge about Cervical Cancer and Pap Smear and the Factors Influencing the Pap
test Screening among Women.
AB - BACKGROUND: Although the Pap smear is known as one of the effective methods to
detect the cervical cancer, a large group of women are reluctant to do the test
because of various reasons. Therefore, we carried out this study to determine the
level of knowledge about cervical cancer and Pap smear and the factors
influencing the Pap test screening among women. METHODS: In this cross-sectional
study, 355 women referred to the health centers of Gilan-e gharb city were
randomly recruited in 2015. The participants asked to complete a self
administered questionnaire including five parts (questions about: demographic
factors, knowledge about cervical cancer and Pap smear, Pap smear performance,
barriers and facilitators related to Pap smear and the sources of information).
Data were analyzed through SPSS version 19, using descriptive statistics,
Independent T-test, and logistic regression. RESULTS: The mean age of the
participants was 34.08+/-7.81 years. Almost 50.4% of the subjects had a history
of Pap smear test. Pap test performance was significantly higher in those who had
higher knowledge (P<0.001). Knowledge about cervical cancer, Pap smear and age
was the most important predictors of the Pap test performance (P<0.001). The most
important barrier and facilitator to Pap smear test were inadequate knowledge and
the recommendations received from family, friends and healthcare professionals
(44.3% and 40.2%, respectively). CONCLUSION: Knowledge about Pap smear and
cervical cancer was important in predicting Pap test doing. In addition,
inadequate knowledge was introduced as the most important barrier to screening
test from the perspective of women. Therefore, we suggest that health education
and health promotion studies as interdisciplinary and targeted interventions
should be implemented to improve the women's knowledge.
PMID- 28409173
TI - Does Spousal Support Can Increase the Women's Physical Activity?
AB - BACKGROUND: Numerous benefits of physical activity are well-known for the
prevention and treatment of various diseases such as diabetes, cardiovascular
disease, obesity, and cancers. However, the status of physical activities among
women remains noticeably less than the recommended level. Considering the
importance of the spouses' participation in the promotion of women's health, this
study examined the impact of spousal support on women's physical activity.
METHODS: This semi--experimental study was done in February 2015 on 100 couples
in reproductive age referred to health centers of Falavarjan city. The
participants were randomly divided into intervention and control groups. The
information related to women's physical activity in both groups was collected by
aquestionnaire in two steps, before and three months after the intervention. The
spouses of women in the intervention group were trained in the field of the
importance of physical activity in women's health in two sessions. The data were
analyzed by the software SPSS21 and suitable statistical tests (Independent t,
paired t, and Chi-square). RESULTS: The mean and standard deviation of women's
age in the both groups were 28.76+/-5.51 and 30.38+/-5.31, respectively. The
prevalence of obesity and overweight in the women under the study was generally
estimated 44%. Physical activities of women in the intervention group were
significantly increased after the intervention (P<0.0001). Also, the Body Mass
Index in the intervention group was significantly decreased compared to before
the intervention and control group (P<0.001). CONCLUSION: Spouses could encourage
women to perform physical activities. It is recommended that the health care
system should implement educational sessions for men to encourage women to
exercise.
PMID- 28409174
TI - Neurokinin 1 and opioid receptors: relationships and interactions in nervous
system.
AB - Opioid receptors and neurokinin 1 receptor (NK1R) are found highly expressed in
the central nervous system. The co-localization of these two kinds of receptors
suggests that they might interact with each other in both the transmission and
modulation of the pain signal. In this review, we explore the relationships
between opioid receptors and NK1R. Substance P (SP) plays a modulatory role in
the pain transmission by activating the NK1R. Opioid receptor activation can
inhibit SP release. NK1R is found participating in the mechanisms of the side
effects of the opioids, including opioid analgesic tolerance, hyperalgesia,
anxiety behaviors of morphine reward and opioids related respiratory depression.
A series of compounds such as NK1R antagonists and ligands works on both mu/delta
opioid receptor (MOR/DOR) and NK1R were synthesized as novel analgesics that
enhance the clinical pain management efficacy and reduce the dosage and side
effects. The current status of these novel ligands and the limitations are
discussed in this review. Although the working mechanisms of these ligands
remained unclear, they could be used as research tool for developing novel
analgesic drugs in the future.
PMID- 28409175
TI - CT arthrography of adhesive capsulitis of the shoulder: Are MR signs applicable?
AB - OBJECTIVE: To determine if diagnostic signs of adhesive capsulitis (AC) of the
shoulder at Magnetic Resonance Imaging (MRI) and arthrography (MRA) are
applicable to CT arthrography (CTA). METHODS: 22 shoulder CTAs with AC were
retrospectively reviewed for features described in MR literature. The control
group was composed of 83 shoulder CTA divided into four subgroups 1) normal (N =
20), 2) omarthrosis (N = 19), 3) labral injury (N = 23), and 4) rotator cuff tear
(N = 21). Two musculoskeletal radiologists assessed the rotator interval (RI) for
obliteration, increased width and thickening of coracohumeral ligament (CHL). The
width and capsule thickness of the axillary recess were measured. RESULTS: The
width of the axillary recess was significantly decreased in the AC group (4.6 +/-
2.6 mm versus 9.9 +/- 4.6 mm, p <= 0.0001; sensitivity and specificity of 84% and
80%). Thickness of the medial and lateral walls of the axillary capsule was
significantly increased in the AC group (5.9 +/- 1.3 mm versus 3.7 +/- 1.1 mm, p
<= 0.0001 and 5.7 +/- 1 mm versus 3.5 +/- 1.3 mm, p <= 0.0001, respectively). CHL
thickness was significantly increased in the AC group (4.1 +/- 1 mm (p <= 0.001))
in comparison to others groups. Obliteration of the RI was statistically
significantly more frequent in patients with AC (72.7% (16/22) vs. 12% (10/83), p
< 0.0001). Width of the RI did not differ significantly between patients and
controls (p >= 0.428). CONCLUSION: Decreased axillary width, and thickened
axillary capsule are MR signs of AC applicable to CTA. Evaluation of rotator
interval seems useful and reproducible only for obliteration.
PMID- 28409176
TI - Systemic analysis of osteoblast-specific DNA methylation marks reveals novel
epigenetic basis of osteoblast differentiation.
AB - DNA methylation is an important epigenetic modification that contributes to the
lineage commitment and specific functions of different cell types. In this study,
we compared ENCODE-generated genome-wide DNA methylation profiles of human
osteoblast with 21 other types of human cells in order to identify osteoblast
specific methylation events. For most of the cell strains, data from two isogenic
replicates were included, resulting in a total of 51 DNA methylation datasets. We
identified 852 significant osteoblast-specific differentially methylated CpGs
(DMCs) and 295 significant differentially methylated regions (DMRs). Significant
DMCs/DMRs were not enriched in CpG islands (CGIs) and promoters, but more
strongly enriched in CGI shores/shelves and in gene body and intergenic regions.
The genes associated with significant DMRs were highly enriched in biological
processes related to transcriptional regulation and critical for regulating bone
metabolism and skeletal development under physiologic and pathologic conditions.
By integrating the DMR data with the extensive gene expression and chromatin
epigenomics data, we observed complex, context-dependent relationships between
DNA methylation, chromatin states, and gene expression, suggesting diverse DNA
methylation-mediated regulatory mechanisms. Our results also highlighted a number
of novel osteoblast-relevant genes. For example, the integrated evidences from
DMR analysis, histone modification and RNA-seq data strongly support that there
is a novel isoform of neurexin-2 (NRXN2) gene specifically expressed in
osteoblast. NRXN2 was known to function as a cell adhesion molecule in the
vertebrate nervous system, but its functional role in bone is completely unknown
and thus worth further investigation. In summary, we reported a comprehensive
analysis of osteoblast-specific DNA methylation profiles and revealed novel
insights into the epigenetic basis of osteoblast differentiation and activity.
PMID- 28409177
TI - Dataset on the changes of neutrophils treated with retinoic acid.
AB - The data presented in this article are related to the research article entitled
"Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils
against cancer cells" (S. Shrestha, S.Y. Kim, Y.J. Young, J.K. Kim, J.M. Lee, M.
Shin, D.K. Song, C.W. Hong, 2017) [1]. This article complements the potential of
retinoic acid to induce changes in effector function of human neutrophils. Here
the datasets describe the rate of apoptosis, changes in numbers of nuclear lobes,
and the expressions of surface markers in human neutrophils in presence or
absence of retinoic acid. The tumor growth in recipient mice with adoptive
transfer of retinoic acid-treated neutrophils was evaluated. The included data is
made publicly available to criticism and extended analysis.
PMID- 28409178
TI - BanglaLekha-Isolated: A multi-purpose comprehensive dataset of Handwritten Bangla
Isolated characters.
AB - BanglaLekha-Isolated, a Bangla handwritten isolated character dataset is
presented in this article. This dataset contains 84 different characters
comprising of 50 Bangla basic characters, 10 Bangla numerals and 24 selected
compound characters. 2000 handwriting samples for each of the 84 characters were
collected, digitized and pre-processed. After discarding mistakes and scribbles,
1,66,105 handwritten character images were included in the final dataset. The
dataset also includes labels indicating the age and the gender of the subjects
from whom the samples were collected. This dataset could be used not only for
optical handwriting recognition research but also to explore the influence of
gender and age on handwriting. The dataset is publicly available at
https://data.mendeley.com/datasets/hf6sf8zrkc/2.
PMID- 28409179
TI - Vulva cancer in Ghana - Review of a hospital based data.
AB - *Seventy- 5% of vulvar cancer cases present with advance disease.*Definitive
radiotherapy/chemoradiation is the main stay of treatment.*One third of patients
default treatment.*Five year survival following radiotherapy was 36.7%.
PMID- 28409180
TI - RGB-D Camera Based Walking Pattern Recognition by Support Vector Machines for a
Smart Rollator.
AB - This paper presents a walking pattern detection method for a smart rollator. The
method detects the rollator user's lower extremities from the depth data of an
RGB-D camera. It then segments the 3D point data of the lower extremities into
the leg and foot data points, from which a skeletal system with 6 skeletal points
and 4 rods is extracted and used to represent a walking gait. A gait feature,
comprising the parameters of the gait shape and gait motion, is then constructed
to describe a walking state. K-means clustering is employed to cluster all gait
features obtained from a number of walking videos into 6 key gait features. Using
these key gait features, a walking video sequence is modeled as a Markov chain.
The stationary distribution of the Markov chain represents the walking pattern.
Three Support Vector Machines (SVMs) are trained for walking pattern detection.
Each SVM detects one of the three walking patterns. Experimental results
demonstrate that the proposed method has a better performance in detecting
walking patterns than seven existing methods.
PMID- 28409181
TI - Why do patients with Parkinson's disease fall? A cross-sectional analysis of
possible causes of falls.
AB - BACKGROUND: Falls in Parkinson's disease (PD) are associated with significant
injury, disability, hospitalization, and reduced quality of life. AIMS: To
identify modifiable medical causes of falls in a cohort of PD patients. METHODS:
Eighty seven PD patients were interviewed and examined using validated scales
assessing motor and nonmotor aspects of PD, comorbidities and medication use. The
frequency of falls in the last month was the primary outcome measure. Falls were
hypothesized to be associated with increasing age, advanced motor severity,
particularly axial features (e.g., freezing and postural instability), and
dyskinesia. Nonmotor features hypothesized to be associated with falls included;
cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and
ophthalmological and medical comorbidities. RESULTS: Fallers had longer disease
duration, higher Levodopa-equivalent doses, greater 'On' time with dyskinesia
(all P < 0.005), and higher scores on some Movement Disorder Society-Unified
Parkinson's Disease Rating Scale items, particularly axial scores. However,
patients with falls did not differ from non-fallers in age or overall motor UPDRS
scores. Severity of psychosis, executive cognitive impairment, autonomic
(particularly cardiovascular) dysfunction and sleep disturbances (particularly
REM sleep behavioral disorder) were significantly associated with falls (all P <
0.005). Fallers more frequently reported use of antidepressants (both tricyclics
and SSRIs) and neuroleptics (P < 0.001), but not hypnotics. There was no
difference in medical comorbidities, ophthalmological assessments, fatigue, and
apathy scores between the groups. In logistic regression analysis, cardiovascular
dysfunction, antidepressant use, and REM sleep behavioral disorder were
significantly associated with falls. CONCLUSIONS: The causes of falls in PD are
multifactorial and extend beyond motor impairment and dyskinesia; addressing
these in patients already treated with dopaminergic medications has the potential
to improve this important complication of PD.
PMID- 28409182
TI - Glutathione Disulfide Liposomes - a Research Tool for the Study of Glutathione
Disulfide Associated Functions and Dysfunctions.
AB - Glutathione disulfide (GSSG) is the oxidized form of glutathione (GSH). GSH is a
tripeptide present in the biological system in mM concentration and is the major
antioxidant in the body. An increase in GSSG reflects an increase in
intracellular oxidative stress and is associated with disease sates. The increase
has also been demonstrated to lead to an increase in protein S-glutathionylation
that can affect the structure and function of proteins. Protein S
glutathionylation serves as a regulatory mechanism during cellular oxidative
stress. Though GSSG is commercially available, its roles in various GSSG
associated normal/abnormal physiological functions have not been fully delineated
due to the reason that GSSG is not cell membrane permeable and a lack of method
to specifically increase GSSG in cells. We have developed cationic liposomes that
can effectively deliver GSSG into cells. Various concentrations of GSSG liposomes
can be conveniently prepared. At 1 mg/mL, the GSSG liposomes effectively
increased intracellular GSSG by 27.1 +/- 6.9 folds (n = 3) in 4 hours and led to
a significant increase in protein S-glutathionylation confirming that the
increased GSSG is functionally effective. The Trypan blue assay demonstrated that
GSSG liposomes were not cytotoxic; the cell viability was greater than 95% after
cells were treated with the GSSG liposomes for 4 h. A stability study showed that
the dry form of the GSSG liposomes were stable for at least 70 days when stored
at -80 degrees C. Our data demonstrate that the GSSG liposomes can be a valuable
tool in studying GSSG-associated physiological/pathological functions.
PMID- 28409184
TI - Comparison of affect changes during the ovulatory phase in women with and without
hormonal contraceptives.
AB - Studies about affect changes during the menstrual cycle and the role of hormones
in these changes have yielded contradictory results. Often research has focused
on the pre-menstrual phase, with few studies paying specific attention to the
affect changes around ovulation. In this research thirty women completed a daily
questionnaire measuring the positive and negative affect during their menstrual
cycle. These women were divided in two groups: hormonally-contracepting and
naturally-cycling. The Positive and Negative Affect Schedule was used to measure
the affect. A Digital Ovulation Test was used to determine the day of ovulation
in the participants not taking hormonal contraceptives by measuring the
Luteinizing Hormone peak. The differences in positive affect (PA) and negative
affect (NA) between groups were examined. The results indicate that during the
ovulatory phase, PA scores are significantly higher in naturally-cycling women
than hormonally-contracepting women.
PMID- 28409183
TI - Combination of IL-10 and IL-2 induces oligoclonal human CD4 T cell expansion
during xenogeneic and allogeneic GVHD in humanized mice.
AB - IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly
divergent immunostimulatory effects under certain conditions. We found high
levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rgammacnull
(NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of
exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution
in vivo, showing an initial delay, followed by rapid expansion. Further, compared
to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival
in most animals and completely protected ~20% of mice from GVHD. Additionally, IL
2 induced expansion of both CD4+ and CD8+ xenoreactive T cells whereas a
combination of IL-2 and IL-10 resulted in selective expansion of CD4+ T cells
only. TCR Vbeta repertoire analysis of CD4+ T cells showed that in contrast to IL
2 alone, simultaneous presence of both cytokines drastically reduced the Vbeta
repertoire of the expanded CD4+ T cells. Highly restricted Vbeta usage was also
observed when the cytokine combination was tested in an allogeneic GVHD model
where NOD-scid IL2rgammacnull mice expressing HLA-DR4 (NSG-DR4) were transplanted
with purified CD4+ T cells from HLA-DR4 negative donors. Taken together, our
results demonstrate that IL-10 can profoundly modulate the subset composition and
repertoire of responding T cells during GVHD.
PMID- 28409185
TI - Ecological risk assessment of agricultural soils for the definition of soil
screening values: A comparison between substance-based and matrix-based
approaches.
AB - The Italian legislation on contaminated soils does not include the Ecological
Risk Assessment (ERA) and this deficiency has important consequences for the
sustainable management of agricultural soils. The present research compares the
results of two ERA procedures applied to agriculture (i) one based on the
"substance-based" approach and (ii) a second based on the "matrix-based"
approach. In the former the soil screening values (SVs) for individual substances
were derived according to institutional foreign guidelines. In the latter, the
SVs characterizing the whole-matrix were derived originally by the authors by
means of experimental activity. The results indicate that the "matrix-based"
approach can be efficiently implemented in the Italian legislation for the ERA of
agricultural soils. This method, if compared to the institutionalized "substance
based" approach is (i) comparable in economic terms and in testing time, (ii) is
site specific and assesses the real effect of the investigated soil on a battery
of bioassays, (iii) accounts for phenomena that may radically modify the exposure
of the organisms to the totality of contaminants and (iv) can be considered
sufficiently conservative.
PMID- 28409186
TI - Social and spatial relationships driving landowner attitudes towards aquatic
conservation in a Piedmont-Blue Ridge landscape.
AB - More than half of land in the U.S. is privately owned and covers most of known
endangered species habitat. An understanding of private landowners' attitudes
towards conservation may help to bridge the science-practice gap in regards to
conservation initiatives. Aquatic biodiversity is particularly imperiled; in the
United States headwaters and isolated wetlands receive little protection through
regulations, becoming a focus of conservation planning. In an effort to assess
how landowners view such efforts, a 27-question mixed methods survey was mailed
to 409 landowners in the Blue Ridge and Piedmont ecoregions of South Carolina
with wetland areas and where land was owned by a family or individual, not a
corporation. We received 70 completed surveys and analyzed the results using an
encapsulated mixed methods approach that analyzed both scaled and qualitative
questions. The combined results gave a more contextual understanding of
conservation on private lands in the study area. In this article we present a
history of private land conservation and surveying landowners in understanding
conservation potential. This demonstrates a need for a more comprehensive method
needed in conservation planning. We then show our use of an integrated
methodology, using quantitative and qualitative questions, to measure landowners'
interest in conserving land. Through classification and spatial analysis, our
study demonstrated that aquatic areas and wildlife are valued by and show
influence on landowners' decisions. We also found that distance from protected
area has a positive correlation to the willingness to protect aquatic areas.
Landowners showed concern for threats of pollution from runoff and siltation.
Disinterest in conservation seemed prevalent throughout many of the respondents'
answers. These results suggest a relation to geographic distance and that the
attitudes are more related near each other and specific places in the landscape.
We conclude that any successful implementation of aquatic conservation
initiatives must include focused outreach and communicating the benefits for
society and landowners for building capacity for landscape-scale cooperation.
PMID- 28409187
TI - Thermodynamic characterisation of urban nocturnal cooling.
AB - Nocturnal cooling of urban areas governs the evolution of thermal state and many
thermal-driven environmental issues in cities, especially those suffer strong
urban heat island (UHI) effect. Advances in the fundamental understanding of the
underlying physics of nighttime UHI involve disentangling complex contributing
effects and remains an open challenge. In this study, we develop new numerical
algorithms to characterize the thermodynamics of urban nocturnal cooling based on
solving the energy balance equations for both the landscape surface and the
overlying atmosphere. Further, a scaling law is proposed to relate the UHI
intensity to a range of governing mechanisms, including the vertical and
horizontal transport of heat in the surface layer, the urban-rural breeze, and
the possible urban expansion. The accuracy of proposed methods is evaluated
against in-situ urban measurements collected in cities with different geographic
and climatic conditions. It is found that the vertical and horizontal
contributors modulate the nocturnal UHI at distinct elevation in the atmospheric
boundary layer.
PMID- 28409188
TI - Comparing object recognition from binary and bipolar edge features.
AB - Edges derived from abrupt luminance changes in images carry essential information
for object recognition. Typical binary edge images (black edges on white
background or white edges on black background) have been used to represent
features (edges and cusps) in scenes. However, the polarity of cusps and edges
may contain important depth information (depth from shading) which is lost in the
binary edge representation. This depth information may be restored, to some
degree, using bipolar edges. We compared recognition rates of 16 binary edge
images, or bipolar features, by 26 subjects. Object recognition rates were higher
with bipolar edges and the improvement was significant in scenes with complex
backgrounds.
PMID- 28409191
TI - The Summit for Cancer Immunotherapy (Summit4CI), June 26-29, 2016 Halifax,
Canada.
PMID- 28409189
TI - Daphnetin reduces endotoxin lethality in mice and decreases LPS-induced
inflammation in Raw264.7 cells via suppressing JAK/STATs activation and ROS
production.
AB - OBJECTIVE: Here, we used various approaches to investigate the suppressive role
of daphnetin in LPS-induced inflammatory response, with the goal to understand
the underlining molecular mechanism by which daphnetin regulated these processes.
METHODS: We examined the survival rate and the lung injury in the mice model of
LPS-induced endotoxemia. The production of pro-inflammatory factors including
tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6,
nitric oxide (NO), and prostaglandin E2 (PGE2) was measured by ELISA and nitrite
analysis, respectively. The expression of inducible NO synthase (iNOS),
cyclooxygenase 2 (COX-2), and the activation of signaling molecules was
determined by immunoblotting. The production of reactive oxygen species (ROS) was
measured by the ROS assay. RESULTS: In vivo study showed that daphnetin enhanced
the survival rate and reduced the lung injury in mice with LPS-induced
endotoxemia. Both in vivo and in vitro study showed that daphnetin prevented the
production of pro-inflammatory factors including TNF-alpha, IL-1beta, IL-6, NO,
and PGE2 after LPS challenge. In Raw264.7 cells, we found that daphnetin reduced
LPS-induced expression of iNOS and COX-2, and suppressed LPS-induced ROS
production. In addition, we found that daphnetin suppressed the activation of
JAK/STATs pathway and inhibited the nucleus import of STAT1 and STAT3.
CONCLUSIONS: Here, our results indicate that daphnetin shows anti-inflammatory
properties, at least in part, through suppressing LPS-induced activation of
JAK/STATs cascades and ROS production.
PMID- 28409190
TI - Methyl-accepting chemotaxis proteins: a core sensing element in prokaryotes and
archaea.
AB - Chemotaxis is the directed motility by means of which microbes sense chemical
cues and relocate towards more favorable environments. Methyl-accepting
chemotaxis proteins (MCPs) are the most common receptors in bacteria and archaea.
They are arranged as trimers of dimers that, in turn, form hexagonal arrays in
the cytoplasmic membrane or in the cytoplasm. Several different classes of MCPs
have been identified according to their ligand binding region and membrane
topology. MCPs have been further classified based on the length and sequence
conservation of their cytoplasmic domains. Clusters of membrane-embedded MCPs
often localize to the poles of the cell, whereas cytoplasmic MCPs can be targeted
to the poles or distributed throughout the cell body. MCPs play an important role
in cell survival, pathogenesis, and biodegradation. Bacterial adaptation to
diverse environmental conditions promotes diversity among the MCPs. This review
summarizes structure, classification, and structure-activity relationship of the
known MCP receptors, with a brief overview of the signal transduction mechanisms
in bacteria and archaea.
PMID- 28409192
TI - Can local radiotherapy and IL-12 synergise to overcome the immunosuppressive
tumor microenvironment and allow "in situ tumor vaccination"?
AB - The abscopal effect, which is the spontaneous regression of tumors or metastases
outside the radiation field, occurs rarely in cancer patients. Interestingly,
radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to
generate tumor-specific cytotoxic CD8+ T cells that are efficient in killing
cancer cells. The key question is: why is this "abscopal effect" so uncommon in
cancer patients treated with RT? Most probably, the main reason may be related to
the highly immunosuppressive tumor microenvironment of well-established tumors
that constantly antagonizes the anti-tumor immune responses triggered by RT. In
this case, additional or combinatorial immunotherapy is needed to attenuate these
immunosuppressive networks and, therefore, substantially increases the efficacy
of RT. Here, we describe a potentially promising synergistic radio-immunotherapy
"in situ tumor vaccination" protocol by antagonizing the tumor-immunosuppressive
microenvironment with a combinatorial approach using local RT and IL-12-based TH1
response augmentation.
PMID- 28409193
TI - Dietary Accumulation of Inorganic Selenium by a Larval Amphibian (Hyla
chrysoscelis) and Influence on Accumulation of Background Mercury.
AB - Larval gray tree frogs (Hyla chrysoscelis) were exposed to inorganic Se (SeO2)
added to the diet (10.2 and 86.3 ug/g dw) and monitored for accumulation and
effect. Background concentrations of Hg were also measured in food and carcasses
to assess possible effects of Se on Hg accumulation. Selenium was accumulated in
a dose dependent manner, and life stages did not differ. No effects of Se
exposure were observed on survival, growth, or time to metamorphosis. Mercury
concentrations in carcasses, resulting from background concentrations in food,
were significantly affected by the presence of Se. In the high Se treatment, Hg
concentrations were significantly decreased relative to those in the low Se
treatment and the control. Our study suggests that exposure to inorganic Se as
SeO2 at the concentrations tested do not elicit adverse biological effects, but
exposure to relatively high concentrations of Se may reduce accumulation of Hg
from food.
PMID- 28409194
TI - Heavy Metals in the Blue Crab (Callinectes sapidus) in Mersin Bay, Turkey.
AB - The concentrations of four metals (copper, cadmium, zinc and lead) were
quantified in blue crabs (Callinectes sapidus) tissues collected in January,
April, June and September at two stations in Mersin Bay, northeastern
Mediterranean Sea, using ICP-MS. The metal concentrations in crabs from the two
stations differed significantly. The hepatopancreas was the major organ
accumulating metals, followed by gill and muscle tissues. Except for lead, the
highest concentrations of metals were measured in the hepatopancreas. The
hepatopancreas had higher concentrations of all heavy metals (Cu 321.1 +/- 4.30;
Zn 182.2 +/- 3.40; Cd 48.2 +/- 2.00) compared to gill (Cu 90.2 +/- 1.35; Zn 104.3
+/- 2.30; Cd 22.3 +/- 3.40) and muscle (Cu 19.1 +/- 1.10; Zn 55.1 +/- 3.25; Cd
2.5 +/- 0.20). Among the metals analyzed, Cu, Zn and Pb were the most abundant in
the different tissues while Cd was the least abundant in C. sapidus. Seasonality
in the levels of the four metals was determined.The highest concentrations of all
metals were observed in the June (Zn 55.1 +/- 3.25; Cu 19.1 +/- 1.10; Cd 2.5 +/-
0.20; Pb 5.1 +/- 0.18) compared to all other months (Zn 34.1 +/- 3.23; Cu 11.1 +/
1.15; Cd 0.9 +/- 0.20; Pb 3.1 +/- 0.21).
PMID- 28409195
TI - Stability of anterior tooth alignment 10 years out of retention.
AB - OBJECTIVE: Long-term posttreatment stability of anterior tooth alignment is of
major interest to both patients and orthodontists. In the present study we
examined the long-term outcome 10 years postretention and investigated the
possible influence of treatment-related factors on posttreatment stability of
maxillary and mandibular anterior tooth alignment. METHODS: The sample comprised
51 patients treated with full fixed appliances in a university clinic. Average
retention time was 1.8 years. All patients received a Hawley appliance in the
maxilla and a bonded canine-to-canine retainer in the mandible. The Peer
Assessment Rating (PAR) Index, Little's Irregularity Index (LII) and dental cast
variables were recorded at pretreatment, posttreatment and 10 years out of
retention. Stability of occlusion was assessed with the PAR score percentage
improvement method. For each jaw a multivariate regression analysis was performed
to identify the influence of treatment-related factors on postretention tooth
alignment. RESULTS: The PAR Index percentage improvement decreased from 73.1%
posttreatment to 53.5% 10 years out of retention. For both jaws posttreatment
increase in anterior irregularity was significantly correlated with the degree of
treatment correction. The strongest association was found in the maxilla.
Premolar extractions were associated with increased stability of mandibular
alignment. CONCLUSIONS: The need for retention appears to increase with the
degree of alignment correction, particularly in the maxilla. Extraction of
premolars significantly improved long-term stability of mandibular incisor
alignment.
PMID- 28409196
TI - Evolutionary Analysis of the Mammalian Tuftelin Sequence Reveals Features of
Functional Importance.
AB - Tuftelin (TUFT1) is an acidic, phosphorylated glycoprotein, initially discovered
in developing enamel matrix. TUFT1 is expressed in many mineralized and non
mineralized tissues. We performed an evolutionary analysis of 82 mammalian TUFT1
sequences to identify residues and motifs that were conserved during 220 million
years (Ma) of evolution. We showed that 168 residues (out of the 390 residues
composing the human TUFT1 sequence) are under purifying selection. Our analyses
identified several, new, putatively functional domains and confirmed previously
described functional domains, such as the TIP39 interaction domain, which
correlates with nuclear localization of the TUFT1 protein, that was demonstrated
in several tissues. We also identified several sites under positive selection,
which could indicate evolutionary changes possibly related to the functional
diversification of TUFT1 during evolution in some lineages. We discovered that
TUFT1 and MYZAP (myocardial zonula adherens protein) share a common ancestor that
was duplicated circa 500 million years ago. Taken together, these findings expand
our knowledge of TUFT1 evolution and provide new information that will be useful
for further investigation of TUFT1 functions.
PMID- 28409197
TI - Variation in Biological Soil Crust Bacterial Abundance and Diversity as a
Function of Climate in Cold Steppe Ecosystems in the Intermountain West, USA.
AB - Biological soil crust (biocrust) is a composite of mosses, lichens, and bacteria
that performs many important soil system functions, including increasing soil
stability, protecting against wind erosion, reducing nutrient loss, and mediating
carbon and nitrogen fixation cycles. These cold desert and steppe ecosystems are
expected to experience directional changes in both climate and disturbance. These
include increased temperatures, precipitation phase changes, and increased
disturbance from anthropogenic land use. In this study, we assessed how climate
and grazing disturbance may affect the abundance and diversity of bacteria in
biocrusts in cold steppe ecosystems located in southwestern Idaho, USA. To our
knowledge, our study is the first to document how biocrust bacterial composition
and diversity change along a cold steppe climatic gradient. Analyses based on 16S
small subunit ribosomal RNA gene sequences identified the phylum Actinobacteria
as the major bacterial component within study site biocrusts (relative abundance
= 36-51%). The abundance of the phyla Actinobacteria and Firmicutes was higher at
elevations experiencing cooler, wetter climates, while the abundance of
Cyanobacteria, Proteobacteria, and Chloroflexi decreased. The abundance of the
phyla Cyanobacteria and Proteobacteria showed no significant evidence of decline
in grazed areas. Taken together, results from this study indicate that bacterial
communities from rolling biocrusts found in cold steppe ecosystems are affected
by climate regime and differ substantially from other cold desert ecosystems,
resulting in potential differences in nutrient cycling and ecosystem dynamics.
PMID- 28409198
TI - [Safe treatment of acute hyperkalemia : The 1:4 and other principles].
AB - Acute hyperkalemia is a dangerous electrolyte disorder, which must be treated
immediately. It can lead to cardiac arrhythmia and death due to alterations in
cell membrane potentials. The resulting alterations in the electrocardiogram
(ECG) are multifarious and need to be rapidly recognized. Treatment consists of
various stages. In addition to membrane stabilization, which is always necessary,
potassium must be displaced into the intracellular space and then eliminated from
the body. A commonly applied method for displacement of potassium into the
intracellular space involves the administration of insulin-glucose mixtures,
which is associated with many complications. In the clinical routine many
prescription variations are applied, which do not always appear to be ideal with
respect to the individual risk-benefit ratio. A practically useful and easily
memorized insulin-glucose mixture has a relationship of 1IU insulin to 4g
glucose. The therapeutic elimination from the body is carried out using an
enhanced diuresis or the utilization of renal replacement procedures. Special
attention must be paid to the continous monitoring of potassium and blood sugar
levels. After overcoming the acute situation, attention must be paid to treatment
of the underlying disorder and if necessary to readjustment of the long-term
medication of the patient.
PMID- 28409199
TI - Disc degeneration on MRI is more prevalent in young elite skiers compared to
controls.
AB - PURPOSE: Evidence-based facts regarding spine abnormalities and back pain are
needed in order to develop rehabilitation programs and prevent spine injuries in
young skiers. The aim therefore is to identify MRI changes in the thoraco-lumbar
spine and the lifetime prevalence of back pain, as well as the association
between them, in young skiers compared to non-athletes. METHODS: Seventy-five
young elite alpine and mogul skiers, age range 16-20 years, were compared with 27
non-athletic controls. All subjects underwent spinal MRI and answered back pain
questionnaires. RESULTS: Fifty-six percent of skiers had at least one disc
Pfirrmann grade >=3 compared to 30% of controls (p = 0.027). Schmorl's nodes
(46%) and disc height reduction (37%) were significantly more prevalent in skiers
compared to controls (0%) (p < 0.001). When all parameters were combined
together, skiers had significantly higher rate of radiological changes than
controls, 82% compared to 54% (p = 0.007). The mean number of discs with
Pfirrmann grade >=3 was 1.1 per individual in skiers (median 1, range 0-6) versus
0.6 in controls (median 0, range 0-3). There was no significant difference in
lifetime prevalence of back pain between skiers (50%) and controls (44%) (n.s.).
MRI abnormalities in skiers did not correlate with lifetime prevalence of back
pain. Skiers had a better health perception than controls (p = 0.026).
CONCLUSION: Alpine skiers have more degenerative disc changes compared to non
athletes, but these changes do not correlate with the lifetime prevalence of back
pain. Lifetime prevalence of back pain is not significantly different between the
groups; however, skiers report more severe pain on VAS score. LEVEL OF EVIDENCE:
II.
PMID- 28409200
TI - Return to sport after shoulder arthroplasty: a systematic review and meta
analysis.
AB - PURPOSE: With increasing incidence and indications for shoulder arthroplasty,
there is an increasing emphasis on the ability to return to sports. The main goal
of this study was to determine the rate of return to sport after shoulder
arthroplasty. METHODS: The Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines were followed to perform this systematic review and meta
analysis. A search was performed on MEDLINE, Scopus, EMBASE, and the Cochrane
Library. The quality of the included studies was evaluated according to the
Methodological Index for Nonrandomized Studies checklist. The main judgement
outcome was the rate of return to sports activity after shoulder arthroplasty and
the level of play upon return (identical or higher/lower level). RESULTS:
Thirteen studies were reviewed, including 944 patients (506 athletes), treated
with shoulder arthroplasty at an average follow-up of 5.1 years (range, 0.5-12.6
years). The most common sports were swimming (n = 169), golf (n = 144), fitness
sports (n = 71), and tennis (n = 63). The overall rate of return to sport was
85.1% (95% CI, 76.5-92.3%), including 72.3% (95% CI, 60.6-82.8%) returning to an
equivalent or improved level of play, after 1-36 months. Patients undergoing
anatomic total shoulder arthroplasty returned at a significantly higher rate
(92.6%) compared to hemiarthroplasty (71.1%, p = 0.02) or reverse total shoulder
arthroplasty (74.9%, p = 0.003). CONCLUSION: Most patients are able to return to
one or more sports following shoulder arthroplasty, with anatomic total shoulder
arthroplasty having the highest rate of return. LEVEL OF EVIDENCE: IV.
PMID- 28409201
TI - Spontaneous polyploidization in cucumber.
AB - KEY MESSAGE: This is the first quantitative estimation of spontaneous polyploidy
in cucumber and we detected 2.2% polyploids in a greenhouse study. We provide
evidence that polyploidization is consistent with endoreduplication and is an on
going process during plant growth. Cucumber occasionally produces polyploid
plants, which are problematic for growers because these plants produce misshaped
fruits with non-viable seeds. In this study, we undertook the first quantitative
study to estimate the relative frequency of spontaneous polyploids in cucumber.
Seeds of recombinant inbred lines were produced in different environments, plants
were grown in the field and greenhouse, and flow cytometry was used to establish
ploidies. From 1422 greenhouse-grown plants, the overall relative frequency of
spontaneous polyploidy was 2.2%. Plants possessed nuclei of different ploidies in
the same leaves (mosaic) and on different parts of the same plant (chimeric). Our
results provide evidence of endoreduplication and polysomaty in cucumber, and
that it is an on-going and dynamic process. There was a significant effect (p =
0.018) of seed production environment on the occurrence of polyploid plants. Seed
and seedling traits were not accurate predictors of eventual polyploids, and we
recommend that cucumber producers rogue plants based on stature and leaf
serration to remove potential polyploids.
PMID- 28409202
TI - Imaging evaluation of ablative margin and index tumor immediately after
radiofrequency ablation for hepatocellular carcinoma: comparison between
multidetector-row CT and MR imaging.
AB - PURPOSE: To prospectively compare multidetector-row CT (MDCT) and MR imaging
(MRI) in the assessment of the ablative margin (AM) and index tumor immediately
after radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) and assess
whether non-contrast MRI with limited sequences (T1- and T2-weighted imaging
only) was superior to a conventional MDCT protocol. METHODS: A total of 33
consecutive patients with 42 HCCs were included in this study. Both MDCT and MR
images were independently reviewed by two radiologists regarding the ability to
visually discriminate between the AM and index tumor, and the AM status within
ablation zones. The AM status was classified as AM-plus (AM completely
surrounding the tumor), AM-zero (AM was partly discontinuous, without protrusion
of the tumor), and AM-minus (AM was partly discontinuous, with protrusion of the
tumor). During the follow-up period, the cumulative local tumor progression rates
were analyzed using the Kaplan-Meier method and Cox proportional hazards model.
To determine the added value of contrast-enhanced MR images, both reviewers
separately evaluated the two sets (unenhanced and enhanced) of MR images.
RESULTS: Visual discrimination between the AM and index tumor was possible in
four (9.5%) and 34 (81%) of the 42 ablation zones using MDCT and MRI,
respectively (p < 0.001). Thirty-eight and four cases were classified as AM-plus
and AM-zero on MDCT images, respectively, whereas the ablation zones were
categorized as AM-plus (n = 32), AM-zero (n = 9), and AM-minus (n = 1) when
examining the MR images. The cumulative incidence of local tumor progression was
significantly lower in cases with AM-plus on MRI (p = 0.007). Contrast-enhanced
MRI had no added value for the assessment of the AM and index tumor. CONCLUSION:
MRI was superior to MDCT for the differential assessment of the AM and index
tumor immediately after RF ablation for HCC. Non-contrast MRI was also superior
to the conventional MDCT protocol.
PMID- 28409204
TI - "Salvage treatment" for infections by extensively- and pan-drug-resistant
pathogens is common and often sub-optimal.
PMID- 28409203
TI - The role of infection models and PK/PD modelling for optimising care of
critically ill patients with severe infections.
AB - Critically ill patients with severe infections are at high risk of suboptimal
antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of
antimicrobials in these patients differ significantly from the patient groups
from whose data the conventional dosing regimens were developed. Use of such
regimens often results in inadequate antimicrobial concentrations at the site of
infection and is associated with poor patient outcomes. In this article, we
describe the potential of in vitro and in vivo infection models, clinical
pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the
design of more effective antimicrobial dosing regimens. Individualised dosing,
based on population PK models and patient factors (e.g. renal function and
weight) known to influence antimicrobial PK, increases the probability of
achieving therapeutic drug exposures while at the same time avoiding toxic
concentrations. When therapeutic drug monitoring (TDM) is applied, early dose
adaptation to the needs of the individual patient is possible. TDM is likely to
be of particular importance for infected critically ill patients, where profound
PK changes are present and prompt appropriate antibiotic therapy is crucial. In
the light of the continued high mortality rates in critically ill patients with
severe infections, a paradigm shift to refined dosing strategies for
antimicrobials is warranted to enhance the probability of achieving drug
concentrations that increase the likelihood of clinical success.
PMID- 28409205
TI - What's wrong in the control of antimicrobial resistance in critically ill
patients from low- and middle-income countries?
PMID- 28409206
TI - Inverted Nipple Correction with Selective Dissection of Lactiferous Ducts Using
an Operative Microscope and a Traction Technique.
AB - BACKGROUND: An inverted nipple is a common congenital condition in young women
that may cause breastfeeding difficulty, psychological distress, repeated
inflammation, and loss of sensation. Various surgical techniques have been
reported for correction of inverted nipples, and all have advantages and
disadvantages. Here, we report a new technique for correction of an inverted
nipple using an operative microscope and traction that results in low recurrence
and preserves lactation function and sensation. METHODS: Between January 2010 and
January 2013, we treated eight inverted nipples in seven patients with selective
lactiferous duct dissection using an operative microscope. An opposite Z-plasty
was added at the junction of the nipple and areola. Postoperatively, traction was
applied through an apparatus made from a rubber gasket attached to a sterile
syringe. Patients were followed up for 15-48 months. RESULTS: Adequate projection
was achieved in all patients, and there was no wound dehiscence or complications
such as infection. Three patients had successful pregnancies and subsequent
breastfeeding that was not adversely affected by the treatment. There was no loss
of sensation in any patient during the postoperative period. CONCLUSION: Our
technique for treating an inverted nipple is effective and preserves lactation
function and nipple sensation. The method maintains traction for a longer period,
which we believe increases the success rate of the surgery for correction of
severely inverted nipples. LEVEL OF EVIDENCE IV: This journal requires that
authors assign a level of evidence to each article. For a full description of
these Evidence-Based Medicine ratings, please refer to the Table of Contents or
the online Instructions to Authors www.springer.com/00266 .
PMID- 28409207
TI - The Precise Repositioning Instrument for Genioplasty and a Three-Dimensional
Printing Technique for Treatment of Complex Facial Asymmetry.
AB - BACKGROUND: Facial asymmetry is very common in maxillofacial deformities. It is
difficult to achieve accurate reconstruction. With the help of 3D printing models
and surgical templates, the osteotomy line and the amount of bone grinding can be
accurate. Also, by means of the precise repositioning instrument, the
repositioning of genioplasty can be accurate and quick. In this study, we present
a three-dimensional printing technique and the precise repositioning instrument
to guide the osteotomy and repositioning, and illustrate their feasibility and
validity. METHODS: Eight patients with complex facial asymmetries were studied. A
precise 3D printing model was obtained. We made the preoperative design and
surgical templates according to it. The surgical templates and precise
repositioning instrument were used to obtain an accurate osteotomy and
repositioning during the operation. Postoperative measurements were made based on
computed tomographic data, including chin point deviation as well as the symmetry
of the mandible evaluated by 3D curve functions. RESULTS: All patients obtained
satisfactory esthetic results, and no recurrences occurred during follow-up. The
results showed that we achieved clinically acceptable precision for the mandible
and chin. The mean and SD of ICC between R-Post and L-Post were 0.973 +/- 0.007.
The mean and SD of chin point deviation 6 months after the operation were 0.63 +/
0.19 mm. CONCLUSION: The results of this study suggest that the three
dimensional printing technique and the precise repositioning instrument could aid
in making better operation designs and more accurate manipulation in orthognathic
surgery for complex facial asymmetry. LEVEL OF EVIDENCE IV: This journal requires
that authors assign a level of evidence to each article. For a full description
of these Evidence-Based Medicine ratings, please refer to the Table of Contents
or the online Instructions to Authors www.springer.com/00266 .
PMID- 28409208
TI - Inhibitors of ceramide de novo biosynthesis rescue damages induced by cigarette
smoke in airways epithelia.
AB - Exposure to cigarette smoke represents the most important risk factor for the
development of chronic obstructive pulmonary disease (COPD). COPD is
characterized by chronic inflammation of the airways, imbalance of proteolytic
activity resulting in the destruction of lung parenchyma, alveolar hypoxia,
oxidative stress, and apoptosis. Sphingolipids are structural membrane components
whose metabolism is altered during stress. Known as apoptosis and inflammation
inducer, the sphingolipid ceramide was found to accumulate in COPD airways and
its plasma concentration increased as well. The present study investigates the
role of sphingolipids in the cigarette smoke-induced damage of human airway
epithelial cells. Lung epithelial cells were pre-treated with sphingolipid
synthesis inhibitors (myriocin or XM462) and then exposed to a mixture of
nicotine, acrolein, formaldehyde, and acetaldehyde, the major toxic cigarette
smoke components. The inflammatory and proteolytic responses were investigated by
analysis of the mRNA expression (RT-PCR) of cytokines IL-1beta and IL-8, and
matrix metalloproteinase-9 and of the protein expression (ELISA) of IL-8.
Ceramide intracellular amounts were measured by LC-MS technique. Ferric-reducing
antioxidant power test and superoxide anion radical scavenging activity assay
were used to assess the antioxidant power of the inhibitors of ceramide
synthesis. We here show that ceramide synthesis is enhanced under treatment with
a cigarette smoke mixture correlating with increased expression of inflammatory
cytokines and matrix metalloproteinase 9. The use of inhibitors of ceramide
synthesis protected from smoke induced damages such as inflammation, oxidative
stress, and proteolytic imbalance in airways epithelia.
PMID- 28409210
TI - How common are foot problems among individuals with diabetes? Diabetic foot
ulcers in the Dutch population.
AB - AIMS/HYPOTHESIS: Contemporary data on diabetic foot ulcer prevalence are scarce.
Most studies were conducted in the 1990s, reporting incidence rates of 1.9-2.6%.
Since then the prevalence of diabetes has doubled and the organisation of
diabetes care has undergone major changes. Up-to-date data that quantify the
occurrence of diabetic foot ulcers are required and could serve as baseline
measures for future studies. METHODS: Individuals with diabetes (n = 81,793) were
identified from the NIVEL (Netherlands institute for health services research)
Primary Care Database, which contains data for standardised routine care and is
representative of the Dutch population. The annual incidence rates of ulcers and
other foot abnormalities were calculated using data collected between 2010 and
2013. To account for inaccuracies, incidence rates were calculated using: (1)
only individuals with a documented foot examination; (2) all individuals; and (3)
individuals with explicit documentation of present/absent foot ulceration.
RESULTS: There were 412 individuals with documented ulceration during the
registration period (0.50%). The annual incidence rate of foot ulcers was 0.34%
(range 0.22-1.08%). Of those individuals with a documented foot examination,
14.6% had absent pedal pulsations, 17.3% had neuropathy and 10.1% had
callus/pressure marks. CONCLUSIONS/INTERPRETATION: The annual incidence rate of
foot ulcers in the current study was lower than previously reported. This
observation could reflect the efficacy of screening practices and an increased
awareness among professionals and patients. Nevertheless, approximately one in
every five diabetic individuals had at least one identifiable risk factor on foot
examination. This signifies the importance of preventive screening.
PMID- 28409209
TI - 2-Acetyl-5-tetrahydroxybutyl imidazole (THI) protects 661W cells against
oxidative stress.
AB - Retinal degeneration and in particular retinitis pigmentosa (RP) is associated to
ceramide (Cer) accumulation and cell death induction. Cer and sphingosine-1
phosphate (S1P) belong to the sphingolipids class and exert a pro-apoptotic and
pro-survival activity, respectively. Our aim is to target sphingolipid metabolism
by inhibiting S1P lyase that regulates one of the S1P degradation pathways, to
reduce retinal photoreceptor damage. The murine 661W cone-like cell line was
pretreated with THI, an inhibitor of S1P lyase and exposed to H2O2-induced
oxidative stress. 661W cell viability and apoptosis were evaluated by Trypan Blue
and TUNEL assay, respectively. Protein expression of mediators of the
survival/death pathway (ERK1/2, Akt, Bcl-2, Bax) was analyzed by Western
blotting. RT-PCR was performed to establish HO-1 transcript changes and LC-MS
analysis to measure Cer intracellular content. THI rescues inhibitory H2O2-effect
on 661W cell viability and impairs H2O2-induced apoptosis by increasing Bcl-2/Bax
ratio. THI administration counteracts the oxidative stress effects of H2O2 on
661W cells by activating the Nrf2/HO-1 pathway, regulating ERK and Akt
phosphorylation levels, and decreasing Cer intracellular content. We conclude
that sphingolipid metabolism manipulation can be considered a therapeutic target
to promote photoreceptor survival.
PMID- 28409211
TI - Risks of asphyxia-related neonatal complications in offspring of mothers with
type 1 or type 2 diabetes: the impact of maternal overweight and obesity.
AB - AIMS/HYPOTHESIS: We aimed to compare the risks of severe asphyxia-related
neonatal complications in the offspring of mothers with type 1 or type 2
diabetes, and to assess the impact of maternal overweight/obesity on these risks.
METHODS: This was a population-based study of 1,343,751 live-born singleton
infants in Sweden between 1997 and 2011, including 5941 and 711 infants of
mothers with type 1 and type 2 diabetes, respectively. ORs with 95% CIs were
calculated for low Apgar score (0-6) at 5 min after birth, hypoxic ischaemic
encephalopathy and neonatal seizures. RESULTS: The rates of a low Apgar score
were 0.9%, 2.6% and 2.1% in the offspring of mothers without diabetes or with
type 1 or type 2 diabetes, respectively. After controlling for maternal
confounders (including BMI), the risk of a low Apgar score increased in the
offspring of mothers with type 1 diabetes (OR 2.67, 95% CI 2.23, 3.20) but not in
the offspring of mothers with type 2 diabetes (OR 1.25, 95% CI 0.66, 2.35). The
ORs of hypoxic ischaemic encephalopathy or neonatal seizures were increased in
the offspring of mothers with type 1 diabetes (OR 3.41, 95% CI 2.58, 4.49) and
type 2 diabetes (OR 2.54, 95% CI 1.13, 5.69). Maternal overweight/obesity was a
risk factor for asphyxia-related neonatal complications and low Apgar scores in
the offspring of mothers with type 1 diabetes and mothers without diabetes.
CONCLUSIONS/INTERPRETATION: The risks of a low Apgar score and severe asphyxia
related neonatal complications are increased in the offspring of mothers with
type 1 or type 2 diabetes. Maternal overweight/obesity is an important
contributing factor.
PMID- 28409212
TI - Trajectories of glycaemia, insulin sensitivity and insulin secretion in South
Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal
analysis from the Whitehall II cohort study.
AB - AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and
increased risk of type 2 diabetes compared with white individuals. Temporal
changes in glycaemic traits during middle age suggest that impaired insulin
secretion is a particular feature of diabetes development among South Asians. We
therefore aimed to examine ethnic differences in early changes in glucose
metabolism prior to incident type 2 diabetes. METHODS: In a prospective British
occupational cohort, subject to 5 yearly clinical examinations, we examined
ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load
plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin
(2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the
Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white
participants who developed diabetes during follow-up (1991-2013). We fitted cubic
mixed-effects models to longitudinal data with adjustment for a wide range of
covariates. RESULTS: Compared with white individuals, South Asians had a faster
increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI
0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI
0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at
diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (log e
transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21,
0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before
diagnosis and then declined; the initial increase was faster in white
individuals. ISI0,120 declined steeply in both groups before diagnosis; levels
were lower among South Asians before and at diagnosis. There were no ethnic
differences in 2hPG trajectories. CONCLUSIONS/INTERPRETATION: We observed
different trajectories of plasma glucose, insulin sensitivity and secretion prior
to diabetes diagnosis in South Asian and white individuals. This might be due to
ethnic differences in the natural history of diabetes. South Asian individuals
experienced a more rapid decrease in insulin sensitivity and faster increases in
FPG compared with white individuals. These findings suggest more marked
disturbance in beta cell compensation prior to diabetes diagnosis in South Asian
individuals.
PMID- 28409213
TI - A core outcome set for studies evaluating the effectiveness of prepregnancy care
for women with pregestational diabetes.
AB - AIMS/HYPOTHESIS: The aim of this study was to develop a core outcome set (COS)
for trials and other studies evaluating the effectiveness of prepregnancy care
for women with pregestational (pre-existing) diabetes mellitus. METHODS: A
systematic literature review was completed to identify all outcomes reported in
prior studies in this area. Key stakeholders then prioritised these outcomes
using a Delphi study. The list of outcomes included in the final COS were
finalised at a face-to-face consensus meeting. RESULTS: In total, 17 outcomes
were selected and agreed on for inclusion in the final COS. These outcomes were
grouped under three domains: measures of pregnancy preparation (n = 9), neonatal
outcomes (n = 6) and maternal outcomes (n = 2). CONCLUSIONS/INTERPRETATION: This
study identified a COS essential for studies evaluating prepregnancy care for
women with pregestational diabetes. It is advocated that all trials and other non
randomised studies and audits in this area use this COS with the aim of improving
transparency and the ability to compare and combine future studies with greater
ease.
PMID- 28409214
TI - [Fractures of the upper limbs in childhood and adolescence].
AB - Fractures of the upper limbs are frequent and often need operative treatment in
addition to a well-indicated conservative management. This depends on the
maturity of the nearest growth plate and the local remodeling potential, which is
dependent on age. Following conventional x-ray imaging an individual prognostic
growth analysis leads to the therapeutic decision. Around the elbow and the shaft
of the forearm, criteria are stricter than near the shoulder or wrist. Gilchrist
or Desault bandages as well as braces are adequate for most subcapital and
humeral shaft fractures. The short forearm cast is the method of choice at the
wrist. In the case of osteosynthesis the elastic stable intramedullary nailing
(ESIN) method is the first choice for subcapital humerus, radial neck and shaft
fractures. Screw fixation is usually carried out for epicondylar and condylar
fractures and for supracondylar and wrist fractures K-wires represent the
standard procedure.
PMID- 28409215
TI - High and pointed type of femoral localized reaction frequently extends to
complete and incomplete atypical femoral fracture in patients with autoimmune
diseases on long-term glucocorticoids and bisphosphonates.
AB - : Once a localized reaction (beaking) was detected, discontinuation of
bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide
therapy effectively improved its shape. When the localized reaction was high, of
the pointed type, and/or accompanied by prodromal pain, the risks of complete and
incomplete atypical femoral fracture increased and consideration of prophylactic
fixation for such patients was required. INTRODUCTION: Femoral localized reaction
(localized periosteal thickening of the lateral cortex, beaking) is reported to
precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients
with autoimmune diseases taking BPs and glucocorticoids. The aims of the present
study were to retrospectively investigate the shapes of localized reaction to
consider how to manage the condition. METHODS: Twenty femora of 12 patients with
autoimmune diseases who were on BPs and glucocorticoids exhibited femoral
localized reaction. The heights of localized reaction were measured and the
shapes classified as pointed, arched, and other. Localized reaction changes were
divided into three categories: deterioration, no change, and improvement. A
severe form of localized reaction was defined; this was associated with prodromal
pain, de novo complete AFF, or incomplete AFF with a fracture line at the
localized reaction. RESULTS: The mean height of localized reaction was 2.3 +/-
0.8 mm (range, 1.0-3.7 mm) and the pointed type was 35%. Localized reaction was
significantly higher (3.3 +/- 0.8 vs. 2.1 +/- 0.7 mm; p = 0.003) and the pointed
type more common (78 vs. 27%; p = 0.035) in those with the severe form of
localized reaction. Seven patients with localized reactions discontinued BPs just
after localized reaction was detected, but five continued on BPs for 2 years.
Localized reaction deterioration was more common in patients who continued than
discontinued BPs (100 vs. 29%; p = 0.027). After 2 years, all patients had
discontinued BPs and localized reaction did not deteriorate further in any
patient. CONCLUSIONS: Once a localized reaction was detected, discontinuation of
BPs and switching to vitamin D supplementation or teriparatide therapy
effectively improved it. When the localized reaction was high, of the pointed
type, and/or accompanied by prodromal pain, the risks of complete and incomplete
AFF increased and consideration of prophylactic fixation for such patients was
required.
PMID- 28409217
TI - [Surgical techniques for treatment of vestibular schwannoma].
AB - BACKGROUND: Microsurgical resection of vestibular schwannomas is demanding, even
if not all of these tumors represent a challenge for experienced surgeons. In
order to make the right decisions when it comes to balancing the extent of tumor
resection with preservation of function, the surgeon must possess detailed
knowledge of the surgical techniques and also have mastered these. OBJECTIVE: The
current article describes the state-of-the-art of the three major microsurgical
techniques for resection of vestibular schwannomas, their pearls and their
perils. MATERIALS AND METHODS: The literature-based review of the three surgical
techniques is complemented by a discussion of operative nuances and weighting of
advantages and possible complications based on the authors' own experience.
RESULTS: The translabyrinthine, retrosigmoidal, and subtemporal microsurgical
approaches are well documented in the literature regarding their modifications
and the achievable surgical results. Hearing preservation is possible with the
latter two approaches. The choice of approach and the preservation of neural
function depend primarily on the size of the tumor and pre-existing neurologic
deficits. Preoperative diagnostics and preparation differ only for semi-sitting
patient positioning, where transesophageal echocardiography is required. The
classic surgical techniques have been supplemented by fine-tuned
electrophysiologic monitoring, endoscopic views, special microinstruments, and
intraoperative image guidance. CONCLUSION: The choice of surgical approach often
depends on the personal preference and experience of the surgeon. Preoperative
hearing and tumor extension are the main objective selection criteria.
PMID- 28409216
TI - Oral contraceptive use and fracture risk-a retrospective study of 12,970 women in
the UK.
AB - : In the present retrospective case-control study, we compared 6485 women with
fractures and 6485 women without fractures from 135 general practitioner offices
in the UK. Women without bone fractures were statistically more likely to have
been exposed to oral contraception, depending on their age and therapy duration.
INTRODUCTION: The aim of this analysis was to compare the risk of bone fracture
in women using hormonal contraception with that in women who have never used
hormonal contraception. METHODS: A total of 6485 women (mean age 37.8 years) with
an initial diagnosis of fracture between January 2010 and December 2015 were
identified in 135 doctors' offices in the UK Disease Analyzer database. In this
nested case-control study, each case with a fracture was matched (1:1) to a
control without a fracture for age, index year, and follow-up time. In total,
12,970 individuals were available for analysis. The main outcome of the study was
the risk of fracture as a function of combined oral contraceptive (OC) therapy.
Multivariate logistic regression models were used to determine the effect of OC
therapy and its duration on the risk of fracture in the entire population and in
four age-specific subgroups. RESULTS: Women without bone fractures were
significantly more likely to have used oral contraception (OR 0.81). The usage of
oral contraception was associated with a significantly lower risk of bone
fracture (OR 0.81, 95% CI 0.74-0.90). This effect was strongest in the age groups
18-25 and 26-35 and in patients with an OC treatment duration of more than 1
year. CONCLUSIONS: The present study revealed that women without bone fractures
were significantly more likely to have had exposure to combined oral
contraception, especially where the duration of intake was at least 5 years.
PMID- 28409218
TI - Transmembrane helices containing a charged arginine are thermodynamically stable.
AB - Hydrophobic amino acids are abundant in transmembrane (TM) helices of membrane
proteins. Charged residues are sparse, apparently due to the unfavorable
energetic cost of partitioning charges into nonpolar phases. Nevertheless,
conserved arginine residues within TM helices regulate vital functions, such as
ion channel voltage gating and integrin receptor inactivation. The energetic cost
of arginine in various positions along hydrophobic helices has been
controversial. Potential of mean force (PMF) calculations from atomistic
molecular dynamics simulations predict very large energetic penalties, while in
vitro experiments with Sec61 translocons indicate much smaller penalties, even
for arginine in the center of hydrophobic TM helices. Resolution of this conflict
has proved difficult, because the in vitro assay utilizes the complex Sec61
translocon, while the PMF calculations rely on the choice of simulation system
and reaction coordinate. Here we present the results of computational and
experimental studies that permit direct comparison with the Sec61 translocon
results. We find that the Sec61 translocon mediates less efficient membrane
insertion of Arg-containing TM helices compared with our computational and
experimental bilayer-insertion results. In the simulations, a combination of
arginine snorkeling, bilayer deformation, and peptide tilting is sufficient to
lower the penalty of Arg insertion to an extent such that a hydrophobic TM helix
with a central Arg residue readily inserts into a model membrane. Less favorable
insertion by the translocon may be due to the decreased fluidity of the
endoplasmic reticulum (ER) membrane compared with pure palmitoyloleoyl
phosphocholine (POPC). Nevertheless, our results provide an explanation for the
differences between PMF- and experiment-based penalties for Arg burial.
PMID- 28409219
TI - Carbonylation of atrial myosin prolongs its interaction with actin.
AB - Carbonylation induced by hyperthyroidism suppresses force generation of skeletal
myosin and sliding velocity of actin filaments in an in vitro motility assay.
However, its effects on cardiac myosin at the molecular level have not been
studied. Hyperthyroidism induces a change in expression of myosin heavy chains in
ventricles, which may mask the effect of oxidation. In contrast to ventricular
myosin, expression of myosin heavy chains in the atrium does not change upon
hyperthyroidism and enables investigation of the effect of oxidation on cardiac
myosin. We studied the influence of carbonylation, a type of protein oxidation,
on the motor function of atrial myosin and Ca2+ regulation of actin-myosin
interaction at the level of isolated proteins and single molecules using an in
vitro motility assay and an optical trap. Carbonylation of atrial myosin
prolonged its attached state on actin and decreased maximal sliding velocity of
thin filaments over this myosin but did not affect the calcium sensitivity of the
velocity. The results indicate that carbonylation of atrial myosin induced by
hyperthyroidism can be a rate-limiting factor of atrium contractility and so
participates in the genesis of heart failure in hyperthyroidism.
PMID- 28409221
TI - [18]Fluorodeoxyglucose Positron Emission Tomography for the Textural Features of
Cervical Cancer Associated with Lymph Node Metastasis and Histological Type.
AB - BACKGROUND: In this study, we investigated the correlation between the lymph node
(LN) status or histological types and textural features of cervical cancers on
18F-fluorodeoxyglucose positron emission tomography/computed tomography. METHODS:
We retrospectively reviewed the imaging records of 170 patients with
International Federation of Gynecology and Obstetrics stage IB-IVA cervical
cancer. Four groups of textural features were studied in addition to the maximum
standardized uptake value (SUVmax), metabolic tumor volume, and total lesion
glycolysis (TLG). Moreover, we studied the associations between the indices and
clinical parameters, including the LN status, clinical stage, and histology.
Receiver operating characteristic curves were constructed to evaluate the optimal
predictive performance among the various textural indices. Quantitative
differences were determined using the Mann-Whitney U test. Multivariate logistic
regression analysis was performed to determine the independent factors, among all
the variables, for predicting LN metastasis. RESULTS: Among all the significant
indices related to pelvic LN metastasis, homogeneity derived from the gray-level
co-occurrence matrix (GLCM) was the sole independent predictor. By combining
SUVmax, the risk of pelvic LN metastasis can be scored accordingly. The TLGmean
was the independent feature of positive para-aortic LNs. Quantitative differences
between squamous and nonsquamous histology can be determined using short-zone
emphasis (SZE) from the gray-level size zone matrix (GLSZM). CONCLUSION: This
study revealed that in patients with cervical cancer, pelvic or para-aortic LN
metastases can be predicted by using textural feature of homogeneity from the
GLCM and TLGmean, respectively. SZE from the GLSZM is the sole feature associated
with quantitative differences between squamous and nonsquamous histology.
PMID- 28409222
TI - Incidental splenic nodules found on MR imaging done for assessment of iron
overload in children.
AB - BACKGROUND: MR imaging is used to assess iron overload in patients with
hemoglobinopathies and in those who have undergone multiple blood transfusions.
Sometimes splenic nodules are found incidentally on these examinations and this
may cause diagnostic uncertainty. OBJECTIVE: To determine the prevalence, imaging
characteristics and evolution of splenic nodules found on MR imaging for iron
overload evaluation. MATERIALS AND METHODS: Retrospective review of all MR
imaging examinations performed for iron overload assessment from 2005 to 2015 in
a tertiary pediatric hospital. The presence of focal splenic nodules including
number, size, signal characteristics and changes on follow-up MR imaging were
recorded. Relevant patient clinical information including underlying
hematological disease was also documented. RESULTS: A total of 318 patients had
MR imaging for iron overload assessment. Of these, 25 (8%) had at least one
incidental splenic nodule. Sickle cell disease was present in 22 patients (88%)
and thalassemia in 3 (12%). On intermediate-weighted spin-echo images, the
nodules had high signal intensity compared to the remainder of the spleen in 23
patients (92%) and low signal intensity in the remaining 2 (8%). In all patients
(100%) the nodules showed progressive loss of signal intensity with increasing
echo time values. Follow-up MR imaging was performed in 20 (80%) patients, which
showed an increase in the size of the splenic nodules in 7 patients (35%)
stability in 11 (55%) and a decrease in size in 2 (10%). CONCLUSION: It is not
uncommon to find splenic nodules during MR evaluation of iron overload. In
patients with sickle cell disease, most of these nodules are thought to represent
preserved splenic tissue and appear hyperintense compared to the remainder of the
spleen. They frequently remain stable on follow-up imaging, although about a
third of them may show growth. Awareness of these nodules is important to avoid
concern for potential malignancy and unnecessary investigations.
PMID- 28409220
TI - PET and PET/CT with radiolabeled choline in prostate cancer: a critical
reappraisal of 20 years of clinical studies.
AB - We here aim to provide a comprehensive and critical review of the literature
concerning the clinical applications of positron emission tomography/computed
tomography (PET/CT) with radiolabeled choline in patients with prostate cancer
(PCa). We will initially briefly summarize the historical context that brought to
the synthesis of [11C]choline, which occurred exactly 20 years ago. We have
arbitrarily grouped the clinical studies in three different periods, according to
the year in which they were published and according to their relation with their
applications in urology, radiotherapy and oncology. Studies at initial staging
and, more extensively, studies in patients with biochemical failure, as well as
factors predicting positive PET/CT will be reviewed. The capability of PET/CT
with radiolabeled choline to provide prognostic information on PCa-specific
survival will also be examined. The last sections will be devoted to the use of
radiolabeled choline for monitoring the response to androgen deprivation therapy,
radiotherapy, and chemotherapy. The accuracy and the limits of the technique will
be discussed according to the information available from standard validation
processes, including biopsy or histology. The clinical impact of the technique
will be discussed on the basis of changes induced in the management of patients
and in the evaluation of the response to therapy. Current indications to PET/CT,
as officially endorsed by guidelines, or as routinely performed in the clinical
practice will be illustrated. Emphasis will be made on methodological factors
that might have influenced the results of the studies or their interpretation.
Finally, we will briefly highlight the potential role of positron emission
tomography/magnetic resonance and of new radiotracers for PCa imaging.
PMID- 28409223
TI - The relationships between message passing, pairwise, Kermack-McKendrick and
stochastic SIR epidemic models.
AB - We consider a very general stochastic model for an SIR epidemic on a network
which allows an individual's infectious period, and the time it takes to contact
each of its neighbours after becoming infected, to be correlated. We write down
the message passing system of equations for this model and prove, for the first
time, that it has a unique feasible solution. We also generalise an earlier
result by proving that this solution provides a rigorous upper bound for the
expected epidemic size (cumulative number of infection events) at any fixed time
[Formula: see text]. We specialise these results to a homogeneous special case
where the graph (network) is symmetric. The message passing system here reduces
to just four equations. We prove that cycles in the network inhibit the spread of
infection, and derive important epidemiological results concerning the final
epidemic size and threshold behaviour for a major outbreak. For Poisson contact
processes, this message passing system is equivalent to a non-Markovian pair
approximation model, which we show has well-known pairwise models as special
cases. We show further that a sequence of message passing systems, starting with
the homogeneous one just described, converges to the deterministic Kermack
McKendrick equations for this stochastic model. For Poisson contact and recovery,
we show that this convergence is monotone, from which it follows that the message
passing system (and hence also the pairwise model) here provides a better
approximation to the expected epidemic size at time [Formula: see text] than the
Kermack-McKendrick model.
PMID- 28409225
TI - Stromal lenticule transplantation for management of corneal perforations; one
year results.
AB - PURPOSE: To study application of stromal lenticules extracted by femtolaser small
incision lenticule extraction (SMILE) surgery as a surgical adjuvant to seal
corneal perforations. METHODS: Corneal stromal lenticules obtained through SMILE
surgery with central thickness 100 MUm or more were fixed over corneal
perforation sites using 10-0 nylon interrupted stitches with an overlying single
layer of amniotic membrane. Seven patients who had been followed up for a minimum
of 12 months were assessed using slit-lamp biomicroscopy, fluorescein stain,
tonometry, and best spectacle-corrected visual acuity (BSCVA) measurements.
Postoperative complications were recorded throughout the follow up period.
RESULTS: Corneal perforations had successfully been sealed in all 7 patients; 3
patients (42.9%) exhibited improved postoperative BSCVA. During the follow-up
period of one year, no signs of re-perforation or infections were detected in any
patient. CONCLUSIONS: These early findings suggest that the use of corneal
stromal lenticules could be a safe and efficient surgical adjuvant for corneal
perforation closure with potential clinical application, together with amniotic
membrane, as relatively simple and low cost temporary measures to prepare
perforated corneas for further definitive procedures.
PMID- 28409224
TI - Occupational exposure to respirable crystalline silica and chronic non-malignant
renal disease: systematic review and meta-analysis.
AB - BACKGROUND: While occupational exposure to respirable silica is known to lead to
lung disease, most notably silicosis, its association with chronic kidney disease
is unclear. OBJECTIVES: This review explores the association between occupational
exposure to respirable silica and chronic non-malignant renal disease such as
glomerulonephritis. The evidence has been collected and compiled. Possible
sources of bias are thoroughly discussed. METHODS: Cohort studies with silica
exposure and case-control studies of renal disease were searched in PubMed until
January 2015. Two authors independently abstracted data; any disagreement was
resolved by consulting a third reviewer. A meta-analysis was performed to
evaluate the association to silica exposure. RESULTS: A total of 23 cohort and
four case-control studies were included in the analysis. The meta-analysis of
cohort studies yielded elevated overall SMRs for renal disease. Some studies,
however, included dose-response analyses, most of which did not show a positive
trend. The approaches and results of the case-control studies were very
heterogeneous. CONCLUSIONS: While the studies of cohorts exposed to silica found
elevated SMRs for renal disease, no clear evidence of a dose-response
relationship emerged. The elevated risk may be attributed to diagnostic and
methodological issues. In order to permit a reliable estimation of a possible
causal link, exposed cohorts should be monitored for renal disease, as the
information from mortality studies is hardly reliable in this field.
PMID- 28409226
TI - Daily thermal fluctuations to a range of subzero temperatures enhance cold
hardiness of winter-acclimated turtles.
AB - Although seasonal increases in cold hardiness are well documented for temperate
and polar ectotherms, relatively little is known about supplemental increases in
cold hardiness during winter. Because many animals are exposed to considerable
thermal variation in winter, they may benefit from a quick enhancement of cold
tolerance prior to extreme low temperature. Hatchling painted turtles (Chrysemys
picta) overwintering in their natal nests experience substantial thermal
variation in winter, and recently, it was found that brief subzero chilling of
winter-acclimated hatchlings decreases subsequent chilling-induced mortality,
increases blood concentrations of glucose and lactate, and protects the brain
from cryoinjury. Here, we further characterize that phenomenon, termed 'cold
conditioning', by exposing winter-acclimated hatchling turtles to -3.5, -7.0, or
10.5 degrees C gradually or repeatedly via daily thermal fluctuations over the
course of 5 days and assessing their survival of a subsequent cold shock to a
discriminating temperature of -12.7 degrees C. To better understand the
physiological response to cold conditioning, we measured changes in glucose and
lactate concentrations in the liver, blood, and brain. Cold conditioning
significantly increased cold-shock survival, from 9% in reference turtles up to
74% in cold-conditioned turtles, and ecologically relevant daily thermal
fluctuations were at least as effective at conferring cryoprotection as was
gradual cold conditioning. Cold conditioning increased glucose concentrations, up
to 25 MUmol g-1, and lactate concentrations, up to 30 MUmol g-1, in the liver,
blood, and brain. Turtles that were cold conditioned with daily thermal
fluctuations accumulated more glucose in the liver, blood, and brain, and had
lower brain lactate, than those gradually cold conditioned. Given the thermal
variation to which hatchling painted turtles are exposed in winter, we suggest
that the supplemental protection conferred by cold conditioning, especially that
induced by daily thermal fluctuations, may be important for their overwinter
survival. Investigation into the duration of the cold-conditioning induced
protection and its occurrence in natural field conditions is needed to better
understand its ecological significance. We suggest that future work exploring the
underlying mechanisms of cold conditioning should focus on non-colligative
effects of glucose, expression of small Hsps, changes in membrane structure, and
ion homeostasis.
PMID- 28409227
TI - Evolutionary responses to climate change in a range expanding plant.
AB - To understand the biological effects of climate change, it is essential to take
into account species' evolutionary responses to their changing environments.
Ongoing climate change is resulting in species shifting their geographical
distribution ranges poleward. We tested whether a successful range expanding
plant has rapidly adapted to the regional conditions in its novel range, and
whether adaptation could be driven by herbivores. Furthermore, we investigated if
enemy release occurred in the newly colonized areas and whether plant origins
differed in herbivore resistance. Plants were cloned and reciprocally
transplanted between three experimental sites across the range. Effects of
herbivores on plant performance were tested by individually caging plants with
either open or closed cages. There was no indication of (regional) adaptation to
abiotic conditions. Plants originating from the novel range were always larger
than plants from the core distribution at all experimental sites, with or without
herbivory. Herbivore damage was highest and not lowest at the experimental sites
in the novel range, suggesting no release from enemy impact. Genotypes from the
core were more damaged compared to genotypes from newly colonized areas at the
most northern site in the novel range, which was dominated by generalist slug
herbivory. We also detected subtle shifts in chemical defenses between the plant
origins. Genotypes from the novel range had more inducible defenses. Our results
suggest that plants that are expanding their range with climate change may evolve
increased vigor and altered herbivore resistance in their new range, analogous to
invasive plants.
PMID- 28409228
TI - Diagnosis and treatment of multiple myeloma in Germany: analysis of a nationwide
multi-institutional survey.
AB - A nationwide, multi-institutional survey was performed in 2011 and 2015 to
analyze routine practice for myeloma patients outside clinical trials in Germany.
We contacted university hospitals, community hospitals, and office-based
hematologists in order to enter clinical data from newly diagnosed and relapsed
patients into an online platform. Complete datasets were available for 478 (2011)
and 515 (2015) patients. While median age at diagnosis increased from 70 to 72
years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented
with equal performance status (ECOG 0-1, 2011 66%; 2015 68%). Cytogenetic
analysis was performed in 53% (2011) and 59% (2015). Patients >=70 years, or
patients with comorbidities who were no candidates for autologous transplantation
(ASCT), were less frequently tested for cytogenetic abnormalities (p = 0.001,
respectively). There were more candidates for ASCT >=65 years in 2015 (57%) than
in 2011 (27%). Bortezomib was used in 92% of transplant-eligible and 66% of
transplant-ineligible patients as frontline therapy in 2015. Application of
bortezomib and lenalidomide for the first relapse changed from 2011 (bortezomib
45%; lenalidomide 27%) to 2015 (bortezomib 28%; lenalidomide 54%). For the second
relapse, application of lenalidomide decreased from 2011 (36%) to 2015 (23%).
Pomalidomide entered treatment for the second relapse in 2015 (11% of patients).
Taken together, we demonstrate that results from clinical trials are implemented
into general practice in Germany.
PMID- 28409229
TI - Sphenoid dysplasia in neurofibromatosis type 1: a new technique for repair.
AB - PURPOSE: Sphenoid bone dysplasia in neurofibromatosis type 1 is characterized by
progressive exophthalmos and facial disfiguration secondary to herniation of
meningeal and cerebral structures. We describe a technique for reconstruction of
the sphenoid defect apt at preventing or correcting the ocular globe dislocation.
METHODS: After placement of spinal cerebrospinal fluid drainage to reduce
intracranial pressure, the temporal pole is posteriorly dislocated extradurally.
The greater sphenoid wing defect is identified. A titanium mesh covered by
lyophilized dura, modeled in a curved fashion, is interposed between the bone
defect and the cerebro-meningeal structures with its convex surface over the
retracted temporal pole. RESULTS: The particular configuration of the titanium
mesh allows a self-maintaining position due to the pressure exerted by the brain
over its convex central part with its lateral margins consequently pushed and
self-anchored against the medial and lateral walls of the temporal fossa. Screw
fixation is not needed. The technique utilized in four cases proved to be
reliable at the long-term clinical and neuroradiological controls (6 to 19
years). CONCLUSION: Sphenoid bone dysplasia in NF1, resulting in proptosis and
exophthalmos, is usually progressive. It can be surgically repaired using a
curved titanium mesh with the convexity faced to the temporal pole that is in the
opposite fashion from all the techniques previously introduced. When utilized
early in life, the technique can prevent the occurrence of the orbital and facial
disfiguration.
PMID- 28409230
TI - Binocular rivalry transitions predict inattention symptom severity in adult ADHD.
AB - Attention deficit and hyperactivity disorder (ADHD) is a prevalent childhood
disorder that is often maintained throughout the development and persists into
adulthood. Established etiology models suggest that deficient inhibition
underlies the core ADHD symptoms. While experimental evidence for impaired motor
inhibition is overwhelming, little is known about the sensory inhibition
processes, their changes throughout the development, and the relationship to ADHD
symptoms. Here, we used the well-established binocular rivalry (BR) paradigm to
investigate for the very first time the inhibitory processes related to visual
perception in adults with ADHD. In BR, perception alternates between two
dichoptically presented images throughout the viewing period, with shorter
dominant percept durations and longer transition periods indicating poorer
suppression/inhibition. Healthy controls (N = 28) and patients with ADHD (N = 32)
were presented with two dissimilar images (orthogonal gratings) separately to
each eye through a mirror stereoscope and asked to report their perceptual
experiences. There were no differences between groups in any of the BR markers.
However, an association between transition durations and symptom severity emerged
in the ADHD group. Importantly, an exploratory multiple regression analysis
revealed that inattention symptoms were the sole predictor for the duration of
transition periods. The lack of impairments to sensory inhibition in adult, but
not pediatric ADHD may reflect compensatory changes associated with development,
while a correlation between inhibition and inattention symptoms may reveal an
invariant core of the disorder.
PMID- 28409231
TI - Preoperative right ventricular dysfunction is a strong predictor of 3 years
survival after cardiac surgery.
AB - BACKGROUND: Prognostic value of right ventricular (RV) systolic function is well
established in valvular disease, heart failure but has not been evaluated in
patients undergoing cardiac surgery. OBJECTIVES: The aim of the present study was
to evaluate the prognostic value of preoperative RV dysfunction extensively
evaluated on the basis of a large set of echocardiographic parameters [S', RV
fractional area change (RVFAC), right myocardial performance index (RMPI),
isovolumic acceleration (IVA), RV dP/dt and basal longitudinal strain (BLS)] in a
large population of unselected patient awaiting cardiac surgery. METHODS: We
prospectively studied 400 consecutive patients referred for cardiac surgery, in a
single surgical center. Echocardiography was performed 24 h before surgery and
phone interview assessed the survival status (overall and cardiovascular death) 3
years after surgery. RESULTS: Among 400 patients, 271 were male, mean age was
70.3 +/- 10.2. At 3-years the overall and cardiovascular mortality was,
respectively, 10.5 and 6.8%. The univariate Cox analysis identified all RV
function parameters excepted BLS as predictive factors of overall mortality, with
the strongest value for RVFAC < 35% (HR 4.8), S' < 10 cm/s (HR 3.8) and IVA < 1.8
m/s2 (HR 3.2) (all P < 0.001). All parameters were associated to cardiovascular
mortality. In multivariate analysis, RVFAC, S', dP/dt and IVA were significantly
associated to 3-years overall mortality whatever the EuroSCORE. Abnormal RVFAC,
S', IVA and BLS were associated to cardiovascular mortality. CONCLUSIONS: The
presence of RV dysfunction before cardiac surgery assessed by echo significantly
predicts postoperative mortality, and this is true whatever the EuroSCORE level.
This result demonstrates the need of adding the assessment of echographic RV
function before cardiac surgery.
PMID- 28409233
TI - Effects of a web-based follow-up intervention on self-efficacy in obesity
treatment for women.
AB - Obesity is a chronic disease requiring long-term care. The purpose of the current
study was the evaluation of a web-based intervention (WBI), subsequent to an
initial face to face life style treatment. In a randomized trial, 84 women
received an introduction phase (4 months) and a training phase (2 months) where
one group was trained in using WBI whereas the other arm received a printed
manual (PMI). During the self-monitoring phase (6 months) participants either
used the WBI or the PMI for follow-up support. Anthropometric parameters could be
significantly reduced and self-efficacy was significantly increased in the first
6 months. At 12 months, values of self-efficacy of the WBI were not superior
compared to results of the PMI; however, feedback on acceptability of the
intervention did show higher ratings of the WBI and also facilitated contact with
the program supervisor. No significant differences regarding the engagement in
follow-up tools could be found between the intervention groups. Subgroup analysis
indicated a positive effect of involvement in both forms of self-monitoring
aftercare.
PMID- 28409234
TI - Clinical role of von Willebrand factor in acute ischemic stroke.
AB - BACKGROUND: An elevated level of von Willebrand factor (VWF) is associated with
an increased risk for coronary heart disease and ischemic stroke. The objective
of the study was to determine whether the level of VWF is associated with the
cardioembolic subtype of ischemic stroke, stroke severity, and clinical outcome.
PATIENTS AND METHODS: In this study 108 patients suffering from acute ischemic
stroke (AIS) were included. According to the etiology of the stroke, patients
were classified into the subtype of cardioembolic (CE) stroke and the group with
non-CE stroke. Patients with non-CE stroke were further classified into subtype
of large vessel disease, subtype of small vessel disease and subtype of
cryptogenic stroke. Laboratory tests were performed in the acute phase and VWF
was determined for all patients. The National Institutes of Health Stroke Scale
(NIHSS) was applied on admission and the modified Rankin scale (MRS) at
discharge. RESULTS: The only significant factor which predicted CE stroke was age
(B = 0.077; standard error, SE = 0.026; P = 0.003). The level of VWF was not
significantly higher in the group with the cardioembolic stroke compared to the
group with non-CE stroke. Patients assessed by NIHSS on admission as the most
disabled had significantly higher levels of VWF (B = 0.006; SE = 0.003; P =
0.045). Those with higher scores of MRS at discharge also had significantly
increased levels of VWF (B = 0.006; SE = 0.003; P = 0.028). CONCLUSION: Among the
patients with ischemic stroke, levels of VWF were not increased in those with CE
stroke. High levels of VWF were associated with greater severity of stroke as
well as with poor clinical outcome.
PMID- 28409235
TI - Anal incontinence after two vaginal deliveries without obstetric anal sphincter
rupture.
AB - PURPOSE: To evaluate prevalence and risk factors for long-term anal incontinence
in women with two prior vaginal deliveries without obstetric anal sphincter
injury (OASIS) and to assess the impact of anal incontinence-related symptoms on
quality of life. METHODS: This is a nation-wide cross-sectional survey study. One
thousand women who had a first vaginal delivery and a subsequent delivery, both
without OASIS, between 1997 and 2008 in Denmark were identified in the Danish
Medical Birth Registry. Women with more than two deliveries in total till 2012
were excluded at this stage. Of the 1000 women randomly identified, 763 were
eligible and received a questionnaire. Maternal and obstetric data were retrieved
from the national registry. RESULTS: The response rate was 58.3%. In total, 394
women were included for analysis after reviewing responses according to
previously defined exclusion criteria. Median follow-up time was 9.8 years after
the first delivery and 6.4 years after the second. The prevalence of flatal
incontinence, fecal incontinence and fecal urgency were 11.7, 4.1, and 12.3%,
respectively. Overall, 20.1% had any degree of anal incontinence and/or fecal
urgency. In 6.3% these symptoms affected their quality of life. No maternal or
obstetric factors including episiotomy and vacuum extraction were consistently
associated with altered risk of anal incontinence in the multivariable analyses.
CONCLUSIONS: Anal incontinence and fecal urgency is reported by one fifth of
women with two vaginal deliveries without OASIS at long-term follow-up.
Episiotomy or vacuum extraction did not alter the risk of long-term anal
incontinence.
PMID- 28409237
TI - Prevalence of sucretolerant bacteria in common soils and their isolation and
characterization.
AB - Sucretolerant microbes grow in the presence of sugar concentrations high enough
to substantially lower water activities. Natural habitats high in sugars are
mainly limited to dried fruit, floral nectar, honey, sugarcane, and associated
soils. Organisms that tolerate extremes of solute concentration, high enough to
lower water activities, might not be expected in common oligoosmotic soils. We
report on the isolation of sucretolerant bacteria from common soils using media
supplemented with 50% sucrose (a w 0.91) and their physiological characterization
and identification by 16S rRNA gene phylogeny. Fifteen of these sucretolerant
isolates from common soils were related to four Bacillus spp. A Lysinibacillus
and a Microbacterium (actinomycete) also were collected. All grew at 50% sucrose
and 13 grew at 60% sucrose. Most probable number counts were used to determine
the abundance of sucretolerant microbes in several common soil types, including
agricultural, managed turf, and native prairie. Microbial abundance (with
fungicides) was about 105 and 103 cells g-1 soil in media containing 50 or 70%
sucrose, respectively. The abundances of sucretolerant bacteria in common soils
mirror those of halotolerant bacteria that grow at 10 and 20% NaCl. However,
there is not a correlation between halotolerance and sucretolerance in our
isolates, nor can predictions be made based on taxonomy. Specific solute effects
may be at work, rather than biological responses to a single physicochemical
parameter such as a w. The occurrence of spore-forming sucretolerant bacteria in
common soils has relevance to forward planetary protection and astrobiology.
Extraterrestrial habitable regions are defined in part by tolerance to high
solute concentrations and osmotolerant soil microbes may contaminate spacecraft.
PMID- 28409238
TI - Studies on lipid A isolated from Phyllobacterium trifolii PETP02T
lipopolysaccharide.
AB - The structure of lipid A from lipopolysaccharide of Phyllobacterium trifolii
PETP02T, a nitrogen-fixing symbiotic bacterium, was studied. It was found that
the lipid A backbone was composed of two 2,3-diamino-2,3-dideoxy-D-glucose
(GlcpN3N) residues connected by a beta-(1 -> 6) glycosidic linkage, substituted
by galacturonic acid (GalpA) at position C-1 and partly decorated by a phosphate
residue at C-4' of the non-reducing GlcpN3N. Both diaminosugars were
symmetrically substituted by 3-hydroxy fatty acids (14:0(3-OH) and 16:0(3-OH)).
Ester-linked secondary acyl residues [i.e. 19:0cyc and 28:0(27-OH) or 28:0(27
4:0(3-OMe))] were located in the distal part of lipid A. A high similarity
between the lipid A of P. trifolii and Mesorhizobium was observed and discussed
from the perspective of the genetic context of both genomes.
PMID- 28409236
TI - [Interdisciplinary position paper "Perioperative pain management"].
AB - Despite many positive developments, postoperative pain and its treatment is still
not always given the necessary attention. Severe pain after surgical procedures
affects a significant proportion of patients. This very fact is not only
detrimental to the immediate recovery process, but can also form the basis for
the development of chronic pain conditions.An adequate and effective management
of perioperative pain requires appropriate organizational structures. This
multidisciplinary paper which was initiated by the Austrian Society for
Anaesthesiology and Intensive Care and the Austrian Pain Society and developed
together with numerous specialist and professional societies dealing with the
subject aims at supporting the organization of perioperative pain management
structures and to make best use of proven concepts. Additional recommendations
describe specific interventions for selected types of intervention.
PMID- 28409240
TI - The value of algorithms predicting the Oncotype DX recurrence score should not be
underestimated!
PMID- 28409239
TI - Macrophage activation syndrome in systemic lupus erythematosus: a multicenter,
case-control study in China.
AB - The objective of this study was to describe the clinical and laboratory
characteristics, precipitating factors, treatment, and outcome of macrophage
activation syndrome (MAS) complicating systemic lupus erythematosus (SLE). A
multicenter case-control study was performed across six tertiary hospitals from
1997 to 2014. A total of 32 patients with SLE-associated MAS were enrolled. Sixty
four age- and sex-matched SLE patients diagnosed in the same period without MAS
episodes were selected as controls. The most frequent clinical feature was fever,
followed by splenomegaly. Hyperferritinemia, hypoalbuminemia, and hyper-lactate
dehydrogenase (LDH)-nemia were among the most common laboratory abnormalities.
Compared with pre-MAS visit, patients at the onset of MAS had greater frequencies
of renal involvement, liver dysfunction, and cytopenia. Receiver operating
characteristic (ROC) analysis identified optimal cutoff values of ferritin
(>662.5 ng/mL) and LDH (>359 U/mL) to predict the occurrence of MAS in SLE. SLE
flare and infection were the common triggers of MAS in SLE. Abortion and
parturition were recorded as well. The overall mortality rate was 12.5%. All
patients received corticosteroids. Cyclosporine A, cyclophosphamide, and
etoposide were the three most commonly used immunosuppressants. Rituximab was
given to one patient. Intravenous immunoglobulin (IVIG) was added for 46.9%
patients. MAS is a potentially fatal complication of SLE. Its occurrence is most
frequently associated with active SLE disease or infection. The presentation of
unexplained fever, cytopenia, or liver dysfunction, with high levels of ferritin
and LDH, in patients with SLE should raise the suspicion of MAS. Corticosteroids
with immunosuppressants and IVIG may be an appropriate treatment.
PMID- 28409243
TI - Validation of the Sinhala translation of the International Consultation on
Incontinence Modular Questionnaire for female lower urinary tract symptoms among
women in Sri Lanka.
AB - INTRODUCTION AND HYPOTHESIS: The objective of this study was to translate the
International Consultation on Incontinence Modular Questionnaire for female lower
urinary tract symptoms (ICIQ-FLUTS) into Sinhala and validate the Sinhala
translation for use in clinical practice. METHODS: The ICIQ-FLUTS was translated
into Sinhala in accordance with the ICIQ validation protocol. The Sinhala
translation was validated by administering it to 133 women with FLUTS, mainly
urinary incontinence and or urgency, and to 118 women with symptoms other than
FLUTS during the period 25 October 2013 to 23 December 2016, in the Academic
Obstetrics and Gynaecology Unit, Teaching Hospital Mahamodara, Galle, Sri Lanka.
RESULTS: The Sinhala translation had good content validity (assessed by a panel
of clinicians including a content specialist, and a group of women with and
without FLUTS), good internal consistency (Cronbach's alpha coefficient in the
range 0.69-0.75) was stable (no significant differences between median test
retest scores in a subgroup of 24 women with FLUTS), had good construct validity
(marked difference between median scores in women presenting with and without
FLUTS, p < 0.001), and good responsiveness (marked improvements between scores
before and after treatment, p < 0.001). CONCLUSIONS: The Sinhala translation of
the ICIQ-FLUTS is valid and reliable for assessing Sinhalese-speaking women with
FLUTS, especially urinary incontinence and/or urgency.
PMID- 28409244
TI - Seiza-induced neuropathy: an occupational peroneal neuropathy in a Japanese lady.
PMID- 28409241
TI - MMP11 and CD2 as novel prognostic factors in hormone receptor-negative, HER2
positive breast cancer.
AB - PURPOSE: More accurate prediction of patient outcome based on molecular subtype
is required to identify patients who will benefit from specific treatments.
METHODS: We selected novel 16 candidate prognostic genes, including 10
proliferation-related genes (p-genes) and 6 immune response-related genes (i
genes), from the gene list identified in our previous study. We then analyzed the
association between their expression, measured by quantitative real-time reverse
transcription-PCR in formalin-fixed, paraffin-embedded tissues, and clinical
outcome in 819 breast cancer patients according to molecular subtype. RESULTS:
The prognostic significance of clinical and gene variables varied according to
the molecular subtype. Univariate analysis showed that positive lymph node status
was significantly correlated with the increased risk of distant metastasis in all
subtypes except the hormone receptor-negative, HER2-positive (HR-/HER2+) subtype.
Most p-genes were significantly associated with poor prognosis in patients with
the HR+/HER2- subtype, whereas i-genes correlated with a favorable outcome in
patients with HR-/HER2+ breast cancer. In HR-/HER2+ breast cancer, four genes
(three i-genes BTN3A2, CD2, and TRBC1 and the p-gene MMP11) were significantly
associated with distant metastasis-free survival (DMFS). A new prognostic model
for HR-/HER2+ breast cancer based on the expression of MMP11 and CD2 was
developed and the DMFS for patients in the high-risk group according to our model
was significantly lower than that for those in the low-risk group. Multivariate
analyses revealed that our risk score is an independent prognostic factor for
DMFS. Moreover, C-index showed that our risk score has a superior prognostic
performance to traditional clinicopathological factors. CONCLUSIONS: Our new
prognostic model for HR-/HER2+ breast cancer provides more accurate information
on the risk of distant metastasis than traditional clinical prognostic factors
and may be used to identify patients with a good prognosis in this aggressive
subtype of breast cancer.
PMID- 28409242
TI - Comparison of topical ropivacaine with and without ketamine on post-surgical pain
in children undergoing tonsillectomy: a randomized controlled double-blind study.
AB - PURPOSE: Tonsillectomy in pediatric patients may cause severe postoperative pain.
Topical local anesthetics are an easy and safe way to control post-tonsillectomy
pain, but there is no benefit during the early postoperative stage. Topical
ketamine shows a good effect on early stage postoperative pain. We compared the
effect of topical ropivacaine with and without ketamine on post-tonsillectomy
pain. METHODS: Patients aged 3-7 years undergoing tonsillectomy were selected to
participate in the study. Our study was performed in a randomized, placebo
controlled, double-blind manner. Patients were randomly assigned to one of two
groups using computer-generated random numbers. The researchers who assessed the
pain score, the caregivers, and the patient were blinded to group assignment. One
group received topical ropivacaine with saline (RS group) and the other group
received topical ropivacaine with 20 mg ketamine (RK group) on the tonsillar bed.
Pain scores using the modified Children's Hospital of Eastern Ontario Pain Scale
(mCHEOPS) at 15 min and 30 min, and at 1, 2, 4, 8, 16 and 24 h were recorded.
Rescue analgesic requirement and complications were also recorded. RESULTS: A
total of 66 patients were randomly assigned to the RS group (n = 33) and the RK
group (n = 33). The mCHEOPS scores were significantly lower in the RK group at 15
min (P = 0.046). The mCHEOPS scores of the two groups decreased with time, but
there was no intergroup interaction. The RS group received more analgesics until
1 h after surgery and the RK group received more analgesics during 1-24 h after
surgery. There were no differences in adverse outcomes. CONCLUSIONS: Topical
ropivacaine with ketamine can reduce immediate postoperative pain and analgesic
requirement better than ropivacaine alone.
PMID- 28409245
TI - SNCA 3'UTR genetic variants in patients with Parkinson's disease and REM sleep
behavior disorder.
AB - REM sleep behavior disorder (RBD) is an early marker of Parkinson's disease (PD);
however, it is still unclear which patients with RBD will eventually develop PD.
Single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of
alpha-synuclein (SNCA) have been associated with PD, but at present, no data is
available about RBD. The 3'UTR hosts regulatory regions involved in gene
expression control, such as microRNA binding sites. The aim of this study was to
determine RBD specific genetic features associated to an increased risk of
progression to PD, by sequencing of the SNCA-3'UTR in patients with "idiopathic"
RBD (iRBD) and in patients with PD. We recruited 113 consecutive patients with a
diagnosis of iRBD (56 patients) or PD (with or without RBD, 57 patients).
Sequencing of SNCA-3'UTR was performed on genomic DNA extracted from peripheral
blood samples. Bioinformatic analyses were carried out to predict the potential
effect of the identified genetic variants on microRNA binding. We found three
SNCA-3'UTR SNPs (rs356165, rs3857053, rs1045722) to be more frequent in PD
patients than in iRBD patients (p = 0.014, 0.008, and 0.008, respectively). Four
new or previously reported but not annotated specific genetic variants (KP876057,
KP876056, NM_000345.3:c*860T>A, NM_000345.3:c*2320A>T) have been observed in the
RBD population. The in silico approach highlighted that these variants could
affect microRNA-mediated gene expression control. Our data show specific SNPs in
the SNCA-3'UTR that may bear a risk for RBD to be associated with PD. Moreover,
new genetic variants were identified in patients with iRBD.
PMID- 28409247
TI - [Cetuximab plus chemoradiotherapy for anal carcinoma in immunocompetent patients
does not change existing therapy standards : Results from the prospective,
multicenter E3205 trial].
PMID- 28409246
TI - The impact of androgen deprivation therapy on setup errors during external beam
radiation therapy for prostate cancer.
AB - PURPOSE: To determine whether setup errors during external beam radiation therapy
(RT) for prostate cancer are influenced by the combination of androgen
deprivation treatment (ADT) and RT. MATERIALS AND METHODS: Data from 175 patients
treated for prostate cancer were retrospectively analyzed. Treatment was as
follows: concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent
ADT plus RT, 91 patients (52%); RT only, 51 patients (29%). Required couch shifts
without rotations were recorded for each megavoltage (MV) cone beam computed
tomography (CBCT) scan, and corresponding alignment shifts were recorded as left
right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric
Mann-Whitney test was used to compare shifts by group. Pearson's correlation
coefficient was used to measure the correlation of couch shifts between groups.
Mean prostate shifts and standard deviations (SD) were calculated and pooled to
obtain mean or group systematic error (M), SD of systematic error (Sigma), and SD
of random error (sigma). RESULTS: No significant differences were observed in
prostate shifts in any direction between the groups. Shifts on CBCT were all less
than setup margins. A significant positive correlation was observed between
prostate volume and the z-direction prostate shift (r = 0.19, p = 0.04),
regardless of ADT group, but not between volume and x- or y-direction shifts (r =
0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient
cohorts and ADT groups were similar. CONCLUSION: Hormone therapy given
concurrently with RT was not found to significantly impact setup errors. Prostate
volume was significantly correlated with shifts in the anterior-posterior
direction only.
PMID- 28409248
TI - [Radiotherapy for glioblastoma : ASCO endorses the ASTRO guideline].
PMID- 28409249
TI - [Combining radiation plus temozolomide in glioblastoma patients older than 65
years of age].
PMID- 28409250
TI - Gadolinium-based contrast agents in pediatric magnetic resonance imaging.
AB - Gadolinium-based contrast agents can increase the accuracy and expediency of an
MRI examination. However the benefits of a contrast-enhanced scan must be
carefully weighed against the well-documented risks associated with
administration of exogenous contrast media. The purpose of this review is to
discuss commercially available gadolinium-based contrast agents (GBCAs) in the
context of pediatric radiology. We discuss the chemistry, regulatory status,
safety and clinical applications, with particular emphasis on imaging of the
blood vessels, heart, hepatobiliary tree and central nervous system. We also
discuss non-GBCA MRI contrast agents that are less frequently used or not
commercially available.
PMID- 28409252
TI - Pediatric brain MRI, Part 2: Advanced techniques.
AB - Pediatric neuroimaging is a complex and specialized field that uses magnetic
resonance (MR) imaging as the workhorse for diagnosis. MR protocols should be
tailored to the specific indication and reviewed by the supervising radiologist
in real time. Targeted advanced imaging sequences can be added to provide
information regarding tissue microstructure, perfusion, metabolism and function.
In part 2 of this review, we highlight the utility of advanced imaging techniques
for superior evaluation of pediatric neurologic disease. We focus on the
following techniques, with clinical examples: phase-contrast imaging, perfusion
weighted imaging, vessel wall imaging, diffusion tensor imaging, task-based
functional MRI and MR spectroscopy.
PMID- 28409251
TI - Advanced imaging techniques in pediatric body MRI.
AB - While there are many challenges specific to pediatric abdomino-pelvic MRI, many
recent advances are addressing these challenges. It is therefore essential for
radiologists to be familiar with the latest advances in MR imaging. Laudable
efforts have also recently been implemented in many centers to improve the
overall experience of pediatric patients, including the use of dedicated
radiology child life specialists, MRI video goggles, and improved MR suite
environments. These efforts have allowed a larger number of children to be
scanned while awake, with fewer studies being done under sedation or anesthesia;
this has resulted in additional challenges from patient motion and difficulties
with breath-holding and tolerating longer scan times. In this review, we
highlight common challenges faced in imaging the pediatric abdomen and pelvis and
discuss the application of the newest techniques to address these challenges.
Additionally, we highlight the newest advances in quantified imaging techniques,
specifically in MR liver iron quantification. The techniques described in this
review are all commercially available and can be readily implemented.
PMID- 28409253
TI - Review of key concepts in magnetic resonance physics.
AB - MR physics can be a challenging subject for practicing pediatric radiologists.
Although many excellent texts provide very comprehensive reviews of the field of
MR physics at various levels of understanding, the authors of this paper explain
several key concepts in MR physics that are germane to clinical practice in a non
rigorous but practical fashion. With the basic understanding of these key
concepts, practicing pediatric radiologists can build on their knowledge of
current clinical MR techniques and future advances in MR applications. Given the
challenges of both the increased need for rapid imaging in non-sedated children
and the rapid physiological cardiovascular and respiratory motion in pediatric
patients, many advances in complex MR techniques are being applied to imaging
these children. The key concepts are as follows: (1) structure of a pulse
sequence, (2) k-space, (3) "trade-off triangle" and (4) fat suppression. This
review is the first of five manuscripts in a minisymposium on pediatric MR. The
authors' goal for this review is to aid in understanding the MR techniques
described in the subsequent manuscripts on brain imaging and body imaging in this
minisymposium.
PMID- 28409254
TI - Pediatric brain MRI part 1: basic techniques.
AB - Pediatric neuroimaging is a complex and specialized field that uses magnetic
resonance (MR) imaging as the workhorse for diagnosis. Standard MR techniques
used in adult neuroimaging are suboptimal for imaging in pediatrics because there
are significant differences in the child's developing brain. These differences
include size, myelination and sulcation. MR protocols need to be tailored to the
specific indication and reviewed by the supervising radiologist in real time, and
the specialized needs of this population require careful consideration of issues
such as scan timing, sequence order, sedation, anesthesia and gadolinium
administration. In part 1 of this review, we focus on basic protocol development
and anatomical characterization. We provide multiple imaging examples optimized
for evaluation of supratentorial and infratentorial brain, midline structures,
head and neck, and intracranial vasculature.
PMID- 28409258
TI - Impact of knowledge-based iterative model reconstruction on myocardial late
iodine enhancement in computed tomography and comparison with cardiac magnetic
resonance.
AB - We evaluated the image quality and diagnostic performance of late iodine
enhancement computed tomography (LIE-CT) with knowledge-based iterative model
reconstruction (IMR) for the detection of myocardial infarction (MI) in
comparison with late gadolinium enhancement magnetic resonance imaging (LGE-MRI).
The study investigated 35 patients who underwent a comprehensive cardiac CT
protocol and LGE-MRI for the assessment of coronary artery disease. The CT
protocol consisted of stress dynamic myocardial CT perfusion, coronary CT
angiography (CTA) and LIE-CT using 256-slice CT. LIE-CT scans were acquired 5 min
after CTA without additional contrast medium and reconstructed with filtered back
projection (FBP), a hybrid iterative reconstruction (HIR), and IMR. The signal-to
noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed. Sensitivity
and specificity of LIE-CT for detecting MI were assessed according to the 16
segment model. Image quality scores, and diagnostic performance were compared
among LIE-CT with FBP, HIR and IMR. Among the 35 patients, 139 of 560 segments
showed MI in LGE-MRI. On LIE-CT with FBP, HIR, and IMR, the median SNRs were 2.1,
2.9, and 6.1; and the median CNRs were 1.7, 2.2, and 4.7, respectively.
Sensitivity and specificity were 56 and 93% for FBP, 62 and 91% for HIR, and 80
and 91% for IMR. LIE-CT with IMR showed the highest image quality and sensitivity
(p < 0.05). The use of IMR enables significant improvement of image quality and
diagnostic performance of LIE-CT for detecting MI in comparison with FBP and HIR.
PMID- 28409259
TI - Agreement of tricuspid annular systolic excursion measurement between
transthoracic and transesophageal echocardiography in the perioperative setting.
AB - OBJECTIVE: The aim of our study was to evaluate the level of agreement between
tricuspid annular plane systolic excursion (TAPSE) measured by transthoracic
echocardiography (TTE) and TAPSE measured using transesophageal echocardiography
(TEE) in anesthetized patients. MATERIALS AND METHODS: Thirty patients scheduled
for elective cardiac surgery were prospectively studied. Shortly after induction
of anesthesia before the operation, TAPSE was measured by TTE using M-mode in
apical 4chamber view (4CH) and by TEE in six different views: using 2D
echocardiography in midesophageal (ME) 4CH view, using M-mode in deep
transgastric right ventricle (dTG RV) view at 0 degrees and dTG RV longaxis view
(LAX) as well as using anatomical M-mode (AM-mode) in ME 4CH, dTG RV at 0 degrees
and dTG RV LAX views. RESULTS: Bland-Altman analysis showed a good agreement for
TAPSE measured using M-mode in TTE and using AM-mode in TEE in the ME 4CH and dTG
RV at 0 degrees views (-2.5 +/- 18 and -2.2 +/- 14% respectively). The agreement
between TAPSE measured in TTE and TEE using 2D in ME 4CH, using M-mode in dT GRV
0 degrees and using M-mode and AM-mode in dTG RV LAX view showed a significant
systematic underestimation of the measurements (-8.8 +/- 21, -8.8 +/- 24, -17.8
+/- 28 and -6.4 +/- 20%). CONCLUSION: Our study showed that the right ventricular
function can be accurately and precisely estimated using TAPSE measurement by TEE
in the midesophageal four chamber and deep transgastric right ventricle view at 0
degrees using anatomical M-mode.
PMID- 28409261
TI - [Unclear serous retinal detachment].
PMID- 28409260
TI - The Impact of Teen Court on Rural Adolescents: Improved Social Relationships,
Psychological Functioning, and School Experiences.
AB - Teen Court is a prevention program aimed at diverting first time juvenile
offenders from the traditional juvenile justice system and reintegrating them
into the community. Few studies have examined if Teen Court impacts adolescent
functioning. We examined how Teen Court participation impacted psychosocial
functioning, social relationships, and school experiences in a sample of 392
rural Teen Court participants relative to two comparison samples, one from the
same county as Teen Court (n = 4276) and one from a neighboring county (n =
3584). We found that Teen Court has the potential to decrease internalizing
symptoms, externalizing behavior, violent behavior, parent-adolescent conflict,
and delinquent friends, and increase self-esteem and school satisfaction.
PMID- 28409262
TI - Radioguided occult lesion localization for locally recurrent thyroid carcinoma.
AB - The aim of this study was to present our experiences with patients operated on
for the recurrence of papillary thyroid cancer with the combined use of
preoperative ultrasonographic mapping and radioguided occult lesion localization
(ROLL). Twenty patients who had already undergone total thyroidectomy and
central/lateral neck dissection for papillary thyroid carcinoma were reoperated
on due to locoregional metastasis. The patients with proven recurrences and high
Tg wash-out levels in cytopathologic aspirates were operated on. For each
patient, numbers of marked and non-marked lesions, and the metastatic and total
numbers of marked/non-marked and non-mentioned lesions in the maps were recorded.
Thirty-four of 40 (85%) lesions removed with ROLL were found to be malignant. In
addition to the marked lesions during mapping, 60 additional lesions had been
defined as suspicious. Fifty-six of these lesions were found at exact anatomic
sites and localizations described and removed. Of 56 lesions, 36 (64%) were found
to be metastatic. During postoperative follow-up, chylous leak with spontaneous
regression in 7 days and seroma occurred in one patient. Radioguided occult
lesion localization and preoperative mapping contribute to the safety and comfort
of patients in planned reoperations on lateral and central neck regions.
PMID- 28409263
TI - Gender differences in the bacteriology of rhinosinusitis.
AB - Evaluating gender differences in pathogens involving sinonasal tract disease in
patients undergoing nasal surgery for chronic and recurrent rhinosinusitis (C/R
RS). Retrospective analysis of 164 positive sinonasal swab cultures taken during
endoscopic sinonasal surgery between the years 2006 and 2013. Study population
included 79 (48.8%) female patients and 84 (51/2%) males with a mean age of 47.3
(13-88) years. Positive Staphylococcal growth was found in 38 (23.2%) patients,
positive anaerobic growth in 25 (15.2%) patients and 67 (40.9%) patients had
polymicrobial growth. Staphylococcal growth in the male population was
significantly higher compared to the female population (p = 0.04). Odds ratio for
a polymicrobial infection in males over 60 years old compared to females was 2.17
(CI 0.63-8.08, 95%). Anaerobes were found to be more frequent in males (17.9%)
than in females (12.5%). Species of Streptococci showed no difference between
gender and age groups. The results obtained suggest a difference between the
causing pathogens in C/R RS between females and males. In the male population,
staphylococcal species were found to be significantly more common with a greater
tendency to polymicrobial pathogens and higher rates of anaerobes. These results
might suggest different management protocols perioperatively in males and
females.
PMID- 28409264
TI - A study of the Bodrogkoz population in north-eastern Hungary by Y chromosomal
haplotypes and haplogroups.
AB - We have determined the distribution of Y chromosomal haplotypes and haplogroups
in population samples from one of the most important areas in north-eastern
Hungary from many villages in the Bodrogkoz. The Bodrogkoz region was chosen due
to its isolated nature, because this area was a moorland encircled by the Tisza,
Bodrog, and Latorca Rivers and inhabitants of this part of Hungary escaped from
both Tatar and Ottoman invasions, which decimated the post-Hungarian Conquest
populations in many parts of the country. Furthermore, in the first half of the
tenth century, this region served as the Palatial Centre and burial grounds of
the Hungarian tribes. It has thus been assumed that the present population in
this area is likely to be more similar to the population that lived in the
Conquest period. We analysed male-specific markers, 23 Y-STRs and more than 30 Y
SNPs, that reflect the past and recent genetic history. We found that the general
haplogroup distribution of the samples showed high genetic similarity to non
Bodrogkoz Hungarians and neighbouring populations, despite its sheltered location
and historical record. We were able to classify the Y-chromosomal haplogroups
into four large groups based on STR mutation events: pre-Roman/Roman ancient
lineage, Finno-Ugric speakers arriving into the Carpathian Basin, Migration
period admixture, and post-Hungarian Conquest admixture. It is clear that a
significantly larger database with deep haplogroup resolution, including ancient
DNA data, is required to strengthen this research.
PMID- 28409265
TI - Genomic characterization of bacteriophage vB_PcaP_PP2 infecting Pectobacterium
carotovorum subsp. carotovorum, a new member of a proposed genus in the subfamily
Autographivirinae.
AB - Bacteriophage vB_PcaP_PP2 (PP2) is a novel virulent phage that infects the plant
pathogenic bacterium Pectobacterium carotovorum subsp. carotovorum. PP2 phage has
a 41,841-bp double-stranded DNA encoding 47 proteins, and it was identified as a
member of the family Podoviridae by transmission electron microscopy. Nineteen of
its open reading frames (ORFs) show homology to functional proteins, and 28 ORFs
have been characterized as hypothetical proteins. PP2 phage is homologous to
Cronobacter phage vB_CskP_GAP227 and Dev-CD-23823. Based on phylogenetic
analysis, PP2 and its homologous bacteriophages form a new group within the
subfamily Autographivirinae in the family Podoviridae, suggesting the need to
establish a new genus. No lysogenic-cycle-related genes or bacterial toxins were
identified.
PMID- 28409266
TI - Intimate Partner Violence and PrEP Acceptability Among Low-Income, Young Black
Women: Exploring the Mediating Role of Reproductive Coercion.
AB - A few studies suggest that women who experience intimate partner violence (IPV)
are willing to use pre-exposure prophylaxis (PrEP), but no research has examined
mediators of this relationship. The current study used path analysis to examine a
phenomenon closely associated with IPV: reproductive coercion, or explicit male
behaviors to promote pregnancy of a female partner without her knowledge or
against her will. Birth control sabotage and pregnancy coercion-two subtypes of
reproductive coercion behaviors-were examined as mediators of the relationship
between IPV and PrEP acceptability among a cohort of 147 Black women 18-25 years
of age recruited from community-based organizations in an urban city. IPV
experiences were indirectly related to PrEP acceptability through birth control
sabotage (indirect effect = 0.08; p < 0.05), but not to pregnancy coercion.
Findings illustrate the importance of identifying and addressing reproductive
coercion when assessing whether PrEP is clinically appropriate and a viable
option to prevent HIV among women who experience IPV.
PMID- 28409268
TI - Laparoscopic sigmoid resection for diverticulitis is rarely a suitable case for
the initial phase of the learning curve.
PMID- 28409267
TI - Syringe Sharing Among a Prospective Cohort of Street-Involved Youth: Implications
for Needle Distribution Programs.
AB - The sharing of previously used syringes is associated with the transmission of
Hepatitis C and HIV. This longitudinal study examines syringe borrowing and
syringe lending within a prospective cohort of street-involved youth in
Vancouver, Canada. From September 2005 to May 2014, data were collected from the
At-Risk Youth Study, a cohort of street-involved youth age 14-26 at enrollment,
and analyzed using generalized estimating equations. Among 505 participants, 142
(28.1%) reported syringe borrowing and 132 (26.1%) reported syringe lending
during the study period. In separate multivariable analyses, having difficulty
finding clean needles and homelessness were significantly associated with syringe
borrowing (Adjusted Odds Ratio (AOR) = 2.28, 95% CI 1.66-3.12 and AOR = 1.52, CI
1.05-2.21, respectively) and syringe lending (AOR = 1.89, 95% CI 1.32-2.71 and
AOR = 1.65, 95% CI 1.11-2.44, respectively) (all p values < 0.05). Findings
highlight gaps in syringe access for vulnerable young injectors and suggest that
service delivery for youth may be suboptimal. Further examination of how needle
distribution efforts might be improved to better meet the needs of young people
is warranted.
PMID- 28409269
TI - Short-term outcomes of laparoscopic ventral rectopexy for obstructed defecation
in patients with overt pelvic structural abnormalities-a Chinese pilot study.
AB - AIM: As laparoscopic ventral rectopexy (LVR) gained increasing popularity in the
past decade, studies from non-western area remain rare. The aim of this pilot
study is to evaluate the efficacy and safety of LVR for obstructed defecation
(OD) in Chinese patients with overt pelvic structural abnormalities. METHODS: A
series of 19 consecutive patients is presented undergoing LVR for OD. All
patients showed various forms of pelvic structural abnormalities which were
verified by dynamic defecography exam. Data was prospectively recorded and the
functional outcomes were evaluated using the Cleveland Clinic Constipation Score
(CCCS) and Patients Assessment of Constipation Quality of Life Score (PAC-QoL).
RESULTS: Pelvic structural abnormalities of the 19 patients included external
rectal prolapse (ER) in 10.5% (2/19), high grade internal rectal prolapse (IR) in
57.8% (11/19), rectocele in 52.6% (10/19), enterocele in 15.7% (3/19),
cystocele/vaginal prolapse in 15.7 (3/19), descending perineum (DP) in 63.5%
(12/19). 89.4% patients (17/19) showed at least two co-existed abnormalities and
15.7% (3/19) showed multicompartmental abnormalities. The mean follow-up was 9
months (range 1-18). No mesh-related complication was observed. At last available
follow-up (LAFU), improvement of OD symptom was observed in 15 (78.9%) patients,
the mean scores of CCCS decreased from 17 to 10 (p < 0.05), all four subsets of
PAC-QoL scores improved, and three of them (physical discomfort, worries and
concerns, satisfaction) showed statistical significance (p < 0.05). CONCLUSION:
Laparoscopic ventral rectopexy appears to be a safe and effective procedure for
obstructed defecation in Chinese patients with overt pelvic structural
abnormalities in short-term follow-up.
PMID- 28409270
TI - Getting the first degree relatives to screen for colorectal cancer is harder than
it seems-patients' and their first degree relatives' perspectives.
AB - INTRODUCTION: First degree relatives (FDR) of colorectal cancer (CRC) patients
are at increased risk of CRC compared to the general population. However,
screening colonoscopy rates amongst the FDRs remain dismal. The aim of the study
was to explore the various issues amongst the patients and their FDR precluding
their adoption of screening colonoscopy. METHODS: A qualitative study of CRC
patients and their FDRs was performed. Semi-structured interviews were conducted
with participants using open-ended questions until data saturation was achieved.
These qualitative data were then thematically analysed. RESULTS: Fifty CRC
patients and thirty-one FDRs were recruited between June 2015 and December 2015.
For the patients, three main themes emerged, which include (i) poor understanding
of the CRC screening guidelines for their FDRs, (ii) recommendations are lacking
amongst medical professionals and (iii) numerous barriers are hindering patients
from being advocates for screening colonoscopy for their FDRs. For the FDRs,
three main themes emerged. These include (i) poor understanding of the exact CRC
screening guidelines amongst the FDRs, (ii) the lack of health promotion efforts
amongst medical professionals and (iii) barriers to the uptake of screening
colonoscopy such as fear of colonoscopy, high cost of the procedure, its
associated inconvenience and perceived invulnerability of the individual.
CONCLUSIONS: Patients and FDRs are not aware of the increased risks of developing
CRC amongst the family members. Guidelines regarding screening are also not
clearly understood. The numerous barriers that are present amongst the CRC
patients and their FDRs can be addressed.
PMID- 28409271
TI - Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1
deficiency.
AB - Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging,
nonelastic skin, is of growing significance due to its occurrence in several
different inborn errors of metabolism (IEM). Metabolic cutis laxa results from
Menkes syndrome, caused by a defect in the ATPase copper transporting alpha
(ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7
of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation
(CDG) complex; combined disorder of N- and O-linked glycosylation, due to
mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5
carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency;
macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and
Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations
in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to
mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen
activated pathway (MAP) kinase defects, caused by mutations in several genes
[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto
oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF),
MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide
exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS
proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase
(RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of
inborn errors of metabolism associated with cutis laxa by describing the clinical
presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl
coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a
mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation
spiral of fatty acids and plays an important role in amino acid catabolism,
particularly valine.
PMID- 28409272
TI - Increased trace amine-associated receptor 1 (TAAR1) expression is associated with
a positive survival rate in patients with breast cancer.
AB - PURPOSE: A correlation between breast cancer and thyroid disorders has been
described in previous studies. Degraded thyroid hormones are referred to as trace
amines. These endogenous amines have the ability to bind to the G-protein-coupled
receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1
is able to modulate the serotonergic and dopaminergic system in the brain and has
so far been studied in the neurological field. The following study represents the
first investigation of the regulation of TAAR1 in primary breast cancer (no
metastases, M0). METHODS: Immunohistochemical analyses were carried out to detect
TAAR1 expression in formalin fixed paraffin embedded breast cancer samples.
Survival times of primary breast cancer patients (M0) with and without TAAR1
expression in their tumours were compared by Kaplan-Meier curves, and
correlations between ordinal variables were determined with Spearman's rank
correlation coefficient. RESULTS: The investigation showed a correlation between
TAAR1 expression and tumour differentiation grade. A well differentiated tumour
grade (G1) was associated with higher TAAR1 expression and HER2 and HER4
positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS >= 6)
was associated with significantly longer overall survival (OS) (p = 0.02) than
that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14
years, demonstrating that TAAR1 has a favourable effect on OS of early breast
cancer patients. CONCLUSIONS: We conclude that TAAR1 seems to be an independent
predictor for breast cancer survival. Modulation of TAAR1 may represent a novel
targeting strategy for breast cancer prevention and therapy.
PMID- 28409273
TI - Development of a novel prognostic signature of long non-coding RNAs in lung
adenocarcinoma.
AB - OBJECTIVES: Increasing evidence suggests that long non-coding RNAs (lncRNAs) may
play a crucial role in many biological processes in a variety of cancers and
serve as the basis for many clinical applications including prognostic biomarkers
and potential therapeutic targets. The aim of this study is to develop a
prognostic lncRNA signature with RNA-seq data in lung adenocarcinomas. METHODS:
LncRNA expression profiles and clinical data of lung adenocarcinoma patients from
The Cancer Genome Atlas (TCGA) were analyzed. Univariate Cox proportional
regression model was used to identify prognostic lncRNAs, and then multivariate
Cox proportional regression model was used to develop a prognostic signature.
Survivals were compared using log-rank test, and the biological implications of
prognostic lncRNAs were analyzed using the KEGG pathway functional enrichment
analysis. RESULTS: We identified eight lncRNAs which had prognostic association
with p value <0.01 in a TCGA lung adenocarcinoma cohort of 478 patients. Then a
novel prognostic signature with the eight lncRNAs was developed using Cox
regression model. Signature high-risk cases had worse overall survival (OS,
median 85.97 vs. 38.34 months, p < 0.001) and disease-free survival (DFS, median
44.02 vs. 26.58 months, p = 0.007) than low-risk cases. Multivariate Cox
regression analysis suggested that the eight-lncRNA signature was independent of
clinical and pathological factors. KEGG pathway functional enrichment analysis
indicated potential functional roles of the eight prognostic lncRNAs in
tumorigenesis. CONCLUSIONS: Our findings suggest that the eight-lncRNA signature
might provide an effective independent prognostic model for the prediction of
lung adenocarcinoma patients.
PMID- 28409274
TI - Toward molecular imaging of the free fatty acid receptor 1.
AB - AIMS: Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a
valuable tool for drug development by enabling in vivo target engagement studies
in human. It has also been suggested as a putative target for beta cell imaging,
but the inherent lipophilicity of most FFAR1 binders produces high off-target
binding, which has hampered progress in this area. The aim of this study was to
generate a suitable lead compound for further PET labeling. METHODS: In order to
identify a lead compound for future PET labeling for quantitative imaging of
FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes
([3H]AZ1, [3H]AZ2 and [3H]TAK-875) for their off-target binding, receptor density
and affinity in human pancreatic tissue (islets and exocrine) and rodent
insulinoma. RESULTS: [3H]AZ1 showed improved specificity to FFAR1, with decreased
off-target binding compared to [3H]AZ2 and [3H]TAK-875, while retaining high
affinity in the nanomolar range. FFAR1 density in human islets was approximately
50% higher than in exocrine tissue. CONCLUSIONS: AZ1 is a suitable lead compound
for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity
and reduced off-target binding.
PMID- 28409275
TI - Comment to: sudden death caused by acute pulmonary embolism after laparoscopic
total extraperitoneal inguinal hernia repair: a case report and literature
review. C. Yang, L. Zhu.
PMID- 28409276
TI - A systematic review and meta-analysis of the post-operative adverse effects
associated with mosquito net mesh in comparison to commercial hernia mesh for
inguinal hernia repair in low income countries.
AB - PURPOSE: Abdominal wall hernia is a common surgical condition, with more than 20
million estimated to be repaired each year. Mesh repair is the standard for most
repairs; however, the mesh material itself may be a barrier to care, the cost
prohibitively high for some populations and healthcare systems. The aim of this
systematic review and meta-analysis was to produce a pooled comparison between
the adverse event rate associated with mosquito net mesh and commercial hernia
mesh. METHODS: A systematic review was carried out in accordance with PRISMA
guidelines. PubMed, Ovid Embase/Medline, SCOPUS, Web of Science and the Cochrane
library were searched. In addition, the ISRCTN register, ClinicalTrials.gov, ICTR
Platform and EU Clinical Trials Register were searched. RESULTS: Five randomised
controlled trials (RCTs) were identified. The RCTs were deemed to have similar
sample populations after inspection of their sample parameters. Therefore, the
adverse effects were compared individually (reoccurrence, haematoma, seroma,
infection, and serous discharge) and pooled. A total of 313 mosquito net meshes
were included in the study, there was no significant difference between the
intervention and control groups for pooled adverse effects or individually.
CONCLUSIONS: There is not a significant difference between the commercial mesh
group and the mosquito net mesh group for pooled [odds ratio 0.93 (0.63, 1.35)]
and individual adverse event rates. However, the 95% confidence intervals of
these results are still wide. To reduce this uncertainty sample sizes must
increase in future studies.
PMID- 28409277
TI - A modified Chevrel technique for ventral hernia repair: long-term results of a
single centre cohort.
AB - PURPOSE: To evaluate the short- and long-term results after a modified Chevrel
technique for midline incisional hernia repair, regarding surgical technique,
hospital stay, wound complications, recurrence rate, and postoperative quality of
life. These results will be compared to the literature derived reference values
regarding the original and modified Chevrel techniques. METHODS: In this large
retrospective, single surgeon, single centre cohort all modified Chevrel hernia
repairs between 2000 and 2012 were identified. Results were obtained by reviewing
patients' medical charts. Postoperative quality of life was measured using the
Carolina Comfort Scale. A multi-database literature search was conducted to
compare the results of our series to the literature based reference values.
RESULTS: One hundred and fifty-five patients (84 male, 71 female) were included.
Eighty patients (52%) had a large incisional hernia (width >= 10 cm) according
the definition of the European Hernia Society. Fourteen patients (9%) underwent a
concomitant procedure. Median length-of-stay was 5 days. Within 30 days
postoperative 36 patients (23.2%) had 39 postoperative complications of which 30
were mild (CDC I-II), and nine severe (CDC III-IV). Thirty-one surgical site
occurrences were observed in thirty patients (19.4%) of which the majority were
seroma (16 patients 10.3%). There was no hernia-related mortality during follow
up. Recurrence rate was 1.8% after a median follow-up of 52 months (12-128
months). Postoperative quality of life was rated excellent. CONCLUSIONS: The
modified Chevrel technique for midline ventral hernias results in a moderate
complication rate, low recurrence rate and high rated postoperative quality of
life.
PMID- 28409278
TI - Moderate alcohol consumption is associated with lower chronic disease burden
expressed in disability-adjusted life years: a prospective cohort study.
AB - The relation of alcohol consumption with disease burden remains debated partly
due to opposite associations with cardiovascular disease (CVD) and cancer. The
relation of alcohol consumption with disease burden expressed in disability
adjusted life years (DALYs) summarizes opposing associations of alcohol
consumption on chronic diseases. This study aimed to investigate the association
of alcohol consumption with chronic disease burden expressed in DALYs based on
individual-participant data. The study was a prospective study among 33,066 men
and women from the EPIC-NL cohort. At baseline, alcohol consumption was assessed
with a validated food-frequency questionnaire. Participants were followed for
occurrence of and mortality from chronic diseases and DALYs were calculated.
After 12.4 years follow-up, 6647 disease incidences and 1482 deaths were
documented, resulting in 68,225 healthy years of life lost (6225 DALYs). Moderate
drinkers (women 5-14.9 g/day, men 5-29.9 g/day) had a lower chronic disease
burden (mean DALYs -0.27; 95% CI -0.43; -0.11) than light drinkers (0-4.9 g/day),
driven by a lower disease burden due to CVD (-0.18: -0.29; -0.06) but not cancer
(-0.05: -0.16; 0.06). The associations were most pronounced among older
participants (>=50 years; -0.32; -0.53; -0.10) and not observed among younger
women (-0.08; -0.43; 0.35), albeit non-significant (pinteraction > 0.14).
Substantial drinking (women 15-29.9 g/day, men 30-59.9 g/day) compared to light
drinking was not associated with chronic disease burden. Our results show that
moderate compared to light alcohol consumption was associated with living
approximately 3 months longer in good health. These results were mainly observed
among older participants and not seen among younger women.
PMID- 28409279
TI - Aquaporin 1 controls the functional phenotype of pulmonary smooth muscle cells in
hypoxia-induced pulmonary hypertension.
AB - Vascular remodelling in hypoxia-induced pulmonary hypertension (PH) is driven by
excessive proliferation and migration of endothelial and smooth muscle cells. The
expression of aquaporin 1 (AQP1), an integral membrane water channel protein
involved in the control of these processes, is tightly regulated by oxygen
levels. The role of AQP1 in the pathogenesis of PH, however, has not been
directly addressed so far. This study was designed to characterize expression and
function of AQP1 in pulmonary vascular cells from human arteries and in the mouse
model of hypoxia-induced PH. Exposure of human pulmonary vascular cells to
hypoxia significantly induced the expression of AQP1. Similarly, levels of AQP1
were found to be upregulated in lungs of mice with hypoxia-induced PH. The
functional role of AQP1 was further tested in human pulmonary artery smooth
muscle cells demonstrating that depletion of AQP1 reduced proliferation, the
migratory potential, and, conversely, increased apoptosis of these cells. This
effect was associated with higher expression of the tumour suppressor gene p53.
Using the mouse model of hypoxia-induced PH, application of GapmeR inhibitors
targeting AQP1 abated the hypoxia-induced upregulation of AQP1 and, of note,
reversed PH by decreasing both right ventricular pressure and hypertrophy back to
the levels of control mice. Our data suggest an important functional role of AQP1
in the pathobiology of hypoxia-induced PH. These results offer novel insights in
our pathogenetic understanding of the disease and propose AQP1 as potential
therapeutic in vivo target.
PMID- 28409280
TI - Critical Issues in the Inclusion of Genetic and Epigenetic Information in
Prevention and Intervention Trials.
AB - Human genetic research in the past decade has generated a wealth of data from the
genome-wide association scan era, much of which is catalogued and freely
available. These data will typically test the relationship between a single
nucleotide variant or polymorphism (SNP) and some outcome, disease, or trait.
Ongoing investigations will yield a similar wealth of data regarding epigenetic
phenomena. These data will typically test the relationship between DNA
methylation at a single genomic location/region and some outcome. Most of these
findings will be the result of cross-sectional investigations typically using
ascertained cases and controls. Consequently, most methodological consideration
focuses on methods appropriate for simple case-control comparisons. It is
expected that a growing number of investigators with longitudinal experimental
prevention or intervention cohorts will also measure genetic and epigenetic
indicators as part of their investigations, harvesting the wealth of information
generated by the genome-wide association study (GWAS) era to allow for targeted
hypothesis testing in the next generation of prevention and intervention trials.
Herein, we discuss appropriate quality control and statistical modelling of
genetic, polygenic, and epigenetic measures in longitudinal models. We
specifically discuss quality control, population stratification, genotype
imputation, pathway approaches, and proper modelling of an interaction between a
specific genetic variant and an environment variable (GxE interaction).
PMID- 28409281
TI - Spinal poly-GA inclusions in a C9orf72 mouse model trigger motor deficits and
inflammation without neuron loss.
AB - Translation of the expanded (ggggcc)n repeat in C9orf72 patients with amyotrophic
lateral sclerosis (ALS) and frontotemporal dementia (FTD) causes abundant poly-GA
inclusions. To elucidate their role in pathogenesis, we generated transgenic mice
expressing codon-modified (GA)149 conjugated with cyan fluorescent protein (CFP).
Transgenic mice progressively developed poly-GA inclusions predominantly in
motoneurons and interneurons of the spinal cord and brain stem and in deep
cerebellar nuclei. Poly-GA co-aggregated with p62, Rad23b and the newly
identified Mlf2, in both mouse and patient samples. Consistent with the
expression pattern, 4-month-old transgenic mice showed abnormal gait and
progressive balance impairment, but showed normal hippocampus-dependent learning
and memory. Apart from microglia activation we detected phosphorylated TDP-43 but
no neuronal loss. Thus, poly-GA triggers behavioral deficits through inflammation
and protein sequestration that likely contribute to the prodromal symptoms and
disease progression of C9orf72 patients.
PMID- 28409283
TI - Body composition and lung function in children with cystic fibrosis and meconium
ileus.
AB - : The aim of this study was to explore whether history of meconium ileus (MI) at
birth in children and adolescents with cystic fibrosis (CF) adversely affects
body composition and lung function in later life. Data of children and
adolescents with CF who underwent spirometry and DXA as part of their routine
care were analyzed. Associations between MI (explanatory variable) and areal bone
mineral density (total body less head-TBLH aBMD), lean tissue mass (LTM), and fat
mass (FM) (outcomes) were assessed using general linear models. Potential
relationships of TBLH aBMD, LTM, and FM with FEV1 (additional outcome) were also
explored. One hundred and one subjects with CF (mean age 14 +/- 3 years) were
included, 19 (18.8%) of whom had history of MI. Negative associations were
demonstrated between history of MI and FEV1 (P = 0.04), TBLH aBMD (P = 0.03), and
FM (P < 0.01) but not between history of MI and LTM (P = 0.07) after adjustment
for other variables. Lung function was positively associated with TBLH aBMD (P <
0.01) and LTM (P = 0.02) but not with FM (P = 0.20). CONCLUSION: Among children
and adolescents with CF, those with history of MI have lower bone mineral
density, FM, and lung function. What is Known: * Among children and adolescents
with cystic fibrosis, those with history of meconium ileus in the neonatal period
are at risk of having lower body mass index percentile and FEV 1 percent
predicted. What is New: * Children and adolescents with cystic fibrosis and
history of meconium ileus have decreased bone mineral density and fat mass
compared to patients without such history. * Lower lung function in children with
MI coexists with suboptimal bone mineral density.
PMID- 28409282
TI - Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis.
AB - In the fatal disease-amyotrophic lateral sclerosis (ALS)-upper (corticospinal)
motor neurons (MNs) and lower somatic MNs, which innervate voluntary muscles,
degenerate. Importantly, certain lower MN subgroups are relatively resistant to
degeneration, even though pathogenic proteins are typically ubiquitously
expressed. Ocular MNs (OMNs), including the oculomotor, trochlear and abducens
nuclei (CNIII, IV and VI), which regulate eye movement, persist throughout the
disease. Consequently, eye-tracking devices are used to enable paralysed ALS
patients (who can no longer speak) to communicate. Additionally, there is a
gradient of vulnerability among spinal MNs. Those innervating fast-twitch muscle
are most severely affected and degenerate first. MNs innervating slow-twitch
muscle can compensate temporarily for the loss of their neighbours by re
innervating denervated muscle until later in disease these too degenerate. The
resistant OMNs and the associated extraocular muscles (EOMs) are anatomically and
functionally very different from other motor units. The EOMs have a unique set of
myosin heavy chains, placing them outside the classical characterization spectrum
of all skeletal muscle. Moreover, EOMs have multiple neuromuscular innervation
sites per single myofibre. Spinal fast and slow motor units show differences in
their dendritic arborisations and the number of myofibres they innervate. These
motor units also differ in their functionality and excitability. Identifying the
molecular basis of cell-intrinsic pathways that are differentially activated
between resistant and vulnerable MNs could reveal mechanisms of selective
neuronal resistance, degeneration and regeneration and lead to therapies
preventing progressive MN loss in ALS. Illustrating this, overexpression of OMN
enriched genes in spinal MNs, as well as suppression of fast spinal MN-enriched
genes can increase the lifespan of ALS mice. Here, we discuss the pattern of
lower MN degeneration in ALS and review the current literature on OMN resistance
in ALS and differential spinal MN vulnerability. We also reflect upon the non
cell autonomous components that are involved in lower MN degeneration in ALS.
PMID- 28409285
TI - Urinary calprotectin, kidney injury molecule-1, and neutrophil gelatinase
associated lipocalin for the prediction of adverse outcome in pediatric acute
kidney injury.
AB - : Early identification of patients with acute kidney injury (AKI) being at high
risk for adverse outcome can influence medical treatment. This study compares
urinary calprotectin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase
associated lipocalin (NGAL) for their performance in predicting mortality and
need for renal replacement therapy (RRT) in pediatric AKI patients. Urinary
biomarker concentrations were assessed prospectively in 141 subjects aged 0-18
years including 55 patients with established AKI according to pediatric Risk,
Injury, Failure, Loss, and End-stage kidney disease (pRIFLE) criteria, 27
patients without AKI, and 59 healthy children. Within the AKI group, receiver
operating characteristic (ROC) curve analysis revealed moderate to poor
performance of calprotectin and KIM-1 in the prediction of 30-day mortality
(calprotectin area under the curve (AUC) 0.55; KIM-1 AUC 0.55) and 3-month
mortality (calprotectin AUC 0.61; KIM-1 AUC 0.60) and fair performance in the
prediction of RRT requirement (calprotectin AUC 0.72; KIM-1 AUC 0.71). Urinary
NGAL showed good performance in predicting 30-day (AUC 0.79) and 3-month (AUC
0.81) mortality and moderate performance in predicting RRT (AUC 0.61).
CONCLUSIONS: Whereas urinary calprotectin and KIM-1 can be useful for the
prediction of RRT, urinary NGAL has a good diagnostic performance in predicting
mortality in pediatric patients with AKI of heterogeneous etiology. What is
known: * There is increasing evidence that urinary biomarkers like neutrophil
gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are
valuable for the prediction of adverse outcome in adult acute kidney injury
(AKI), whereas data on pediatric AKI is scarce. What is new: * Urinary
calprotectin and KIM-1 do not predict mortality in our heterogeneous pediatric
AKI cohort, but they show moderate performance in the prediction of dialysis. *
Urinary NGAL is a good predictor of mortality performing better than pRIFLE
stage, eGFR, or creatinine, but it shows moderate performance in the prediction
of dialysis.
PMID- 28409284
TI - Development, prevention, and treatment of feeding tube dependency.
AB - : Enteral nutrition is effective in ensuring nutritional requirements and growth.
However, when tube feeding lasts for a longer period, it can lead to tube
dependency in the absence of medical reasons for continuation of tube feeding.
Tube-dependent children are unable or refuse to start oral activities and they
lack oral skills. Tube dependency has health-, psychosocial-, and economy-related
consequences. Therefore, the transition to oral feeding is of great importance.
However, this transition can be very difficult and needs a multidisciplinary
approach. Most studies for treatment of tube dependency are based on behavioral
interventions, such as family therapy, individual behavior therapy, neuro
linguistic programming, and parental anxiety reduction. Furthermore, oral motor
therapy and nutritional adjustments can be helpful in tube weaning. The use of
medication has been described in the literature. Although mostly chosen as the
last resort, hunger-inducing methods, such as the Graz-model and the Dutch
clinical hunger provocation program, are also successful in weaning children off
tube feeding. CONCLUSION: The transition from tube to oral feeding is important
in tube-dependent children but can be difficult. We present an overview for the
prevention and treatment of tube dependency. What is known: * Longer periods of
tube feeding can lead to tube dependency. * Tube weaning can be very difficult.
What is new: * Weaning as soon as possible and therefore referral to a
multidisciplinary team are recommended. * An overview of treatment options for
tube dependency is presented in this article.
PMID- 28409286
TI - The dependence on ammonia pretreatment of N-O activation by Co(II) sites in
zeolites: a DFT and ab initio molecular dynamics study.
AB - This work is focused on the donor properties of cobalt-exchanged cationic sites
in zeolites. It is based on cluster and periodic density functional theory
modeling for relevant {[Co(II)(NH3)n]-NO} adducts, where Co(II) means a cobalt
cation embedded either in a periodic model of chabasite (CHA) zeolite or in model
clusters. NO stretching frequencies were derived from MD trajectories and
compared to harmonic values from cluster calculations. By relating calculated NO
frequencies to experimental FTIR spectra, it was shown that the forms of {Co(II)
NO} adducts comprising three or four ammonia co-ligands dominate the spectrum
taken in ammonia-saturation conditions while forms with two NH3 ligands prevail
under intermediate ammonia saturation. Finally, this work confirms the critical
dependence of Co(II) activation ability towards NO upon the center donor
properties, reinforced by ligation of strong donor ammonia ligands. However,
strongly bound ligands appear also to compete with interaction of the center with
the electron-rich framework, and a balance must be observed to maintain optimal
activation ability. Graphical abstract A snapshot from MD trajectory showing a
fragment of periodic framework with twoCo(II)-NO centers, bound to one framework
oxygen and strongly coordinating three ammonia ligands with four others forming
the second coordination sphere.
PMID- 28409287
TI - A first-principles study of Ni n Pd n (n = 1 - 5) clusters.
AB - A first-principle investigation of structures and properties of Ni n Pd n (n=1-5)
clusters is presented. For this study, the linear combination of Gaussian-type
orbitals auxiliary density functional theory (LCGTO-ADFT) method has been
employed. In order to determine the lowest energy structures, several isomers in
different spin multiplicities were studied, for each cluster size. Initial
structures, for which successive geometry optimization was computed without any
constrain, were taken along Born-Oppenheimer molecular dynamics (BOMD)
trajectories. To discriminate between minima and transition state structures,
harmonic frequency analyses were performed at the optimized structures. Ground
state structures, bond lengths, harmonic frequencies, dissociation energy,
ionization potential, electron affinity and spin density plots are presented.
This work demonstrates, that the Pd atoms prefer to allocate on the surface of
the cluster structures whose core is formed by the 3d TM atoms type. Moreover, it
has been observed that the ground-state structure spin multiplicity increases as
the system size grows. The results of this study contribute to gain insight into
how structures and energy properties change with cluster size in bimetallic Pd
based alloys.
PMID- 28409288
TI - Temporary fusionless posterior occipitocervical fixation for a proximal
junctional type II odontoid fracture after previous C2-pelvis fusion: case
report, description of a new surgical technique, and review of the literature.
AB - PURPOSE: Axial fractures in patients with a previous C2-pelvis posterior
instrumented fusion are rare and may be challenging to manage. Motion
preservation in the axial spine for these patients is important, as the C1-2 and
Occipit-C1 joints are their only remaining mobile spinal segments. In this unique
report, we present for the first time the use of a fusionless occipitocervical
operation for the treatment of a type II odontoid fracture and unilateral C2 pars
fracture adjacent to a previous C2-pelvis posterior instrumented fusion. METHODS:
Case report. RESULTS: Three years after proximal extension of a T3-pelvis
posterior instrumented fusion to C2, the patient sustained a displaced odontoid
fracture and unilateral C2 pars fracture after a mechanical fall. She underwent
fracture stabilization with extension of instrumentation to the occiput. No
attempt at fusion was performed. Post-operatively, she was distraught by severely
limited neck range of motion, which was reflected in worsening of health-related
quality of life (HRQoL) scores. The fracture healed uneventfully after which the
instrumentation from the occiput and C1 were removed, which resulted in
improvement of neck range of motion. Two years post-operatively, HRQoL scores
showed minimal neck disability (NDI 12), no neck or arm pain (VAS 0), and
outstanding general health (EQ-5D 85 out of 100, SF-36 PCS 35.3, SF-36 MCS 41.1).
CONCLUSION: In this one patient, instrumentation without fusion allowed for
successful and timely union of a displaced odontoid fracture in a patient with a
previous C2-pelvis fusion. Axial range of motion was preserved after
instrumentation removal.
PMID- 28409289
TI - Expert's comment concerning Grand Rounds case entitled "Acute complete paraplegia
of a 8-year-old girl caused by spinal cord infarction following minor trauma
complicated with longitudinal signal change of spinal cord" by K. Nagata et al.
(Eur Spine J, 2017: doi:10.1007/s00586-017-4995-9).
PMID- 28409290
TI - Comparison of clinical and laboratory characteristics during two major paediatric
meningitis outbreaks of echovirus 30 and other non-polio enteroviruses in Germany
in 2008 and 2013.
AB - Viral meningitis is mainly caused by non-polio enteroviruses (NPEV). Large-scale
data on the clinical characteristics between different outbreaks within the same
region are lacking. This study aimed to analyse a possible influence of the
circulating NPEV genotype on the disease outcome of affected children. A
retrospective cohort study analysing two major outbreaks of NPEV meningitis in
Germany in 2008 and 2013 was conducted in cooperation with the National Reference
Centre for Poliomyelitis and Enteroviruses (NRC PE) and five German children's
hospitals. A total of 196 patients with laboratory-confirmed NPEV meningitis were
enrolled. In 2008, children with NPEV meningitis had significantly higher fever
and showed more behavioural changes and less back pain. To better define typical
findings in echovirus 30 (E-30) meningitis, patients were split into the
following three groups: E-30 positive patients, patients with "Non E-30"
infection and patients with "Untyped" NPEV infection. E-30 positive patients were
significantly older and their disease course was more acute, with early admission
to but also early discharge from hospital. E-30 positive patients showed a
significantly higher rate of headache and meningism, and a lower rate of
diarrhoea and clinically defined septicaemia when compared to the others.
Regarding laboratory testing, E-30 positive patients presented with significantly
elevated peripheral blood neutrophil counts when compared to patients with "Non E
30" or "Untyped" NPEV infection. In conclusion, E-30 meningitis in children shows
a characteristic pattern of clinical features. To further characterise NPEV
strains worldwide, continuous surveillance and typing of NPEV strains causing
central nervous system disease is warranted.
PMID- 28409291
TI - Laser Sintered Porous Ti-6Al-4V Implants Stimulate Vertical Bone Growth.
AB - The objective of this study was to examine the ability of 3D implants with
trabecular-bone-inspired porosity and micro-/nano-rough surfaces to enhance
vertical bone ingrowth. Porous Ti-6Al-4V constructs were fabricated via laser
sintering and processed to obtain micro-/nano-rough surfaces. Male and female
human osteoblasts were seeded on constructs to analyze cell morphology and
response. Implants were then placed on rat calvaria for 10 weeks to assess
vertical bone ingrowth, mechanical stability and osseointegration. All
osteoblasts showed higher levels of osteocalcin, osteoprotegerin, vascular
endothelial growth factor and bone morphogenetic protein 2 on porous constructs
compared to solid laser-sintered controls. Porous implants placed in vivo
resulted in an average of 3.1 +/- 0.6 mm3 vertical bone growth and
osseointegration within implant pores and had significantly higher pull-out
strength values than solid implants. New bone formation and pull-out strength was
not improved with the addition of demineralized bone matrix putty. Scanning
electron images and histological results corroborated vertical bone growth. This
study indicates that Ti-6Al-4V implants fabricated by additive manufacturing to
have porosity based on trabecular bone and post-build processing to have micro
/nano-surface roughness can support vertical bone growth in vivo, and suggests
that these implants may be used clinically to increase osseointegration in
challenging patient cases.
PMID- 28409292
TI - Effects of the donor age on proliferation, senescence and osteogenic capacity of
human urine-derived stem cells.
AB - To study the effects of the donor age on the application potential of human urine
derived stem cells (hUSCs) in bone tissue engineering, by comparing
proliferation, senescence and osteogenic differentiation of hUSCs originated from
volunteers with different ages. The urine samples were collected from 19 healthy
volunteers (6 cases from children group aged from 5 to 14, 5 cases from middle
aged group aged from 30 to 40, and 8 cases from the elder group aged from 65 to
75), and hUSCs were isolated and cultured. The cell morphology was observed by
microscope and the cell surface markers were identified by flow cytometry. Their
abilities to undergo osteogenic, adipogenic and chondrogenic differentiation were
determined in vitro, and cell proliferation analyses were performed using Cell
Counting Kit-8 (CCK8) Assay. The senescence of hUSCs among three groups was
assessed by senescence-associated beta galactosidase staining. After osteogenic
differentiation, the alkaline phosphatase (ALP) activity of hUSCs was measured
and expression of osteogenic-related runt-related transcription factor 2 (RUNX2)
and osteocalcin (OCN) was determined by quantitative real-time polymerase chain
reaction (qRT-PCR) and western blot. The hUSCs isolated from urine samples were
adherent cells displayed "rice gain"-like and "spindle-shaped" morphology,
expressing surface markers of mesenchymal stem cells (MSCs) (CD73, CD90, CD105)
and the peripheral cell marker (CD146), but not hematopoietic stem cell markers
(CD34, CD45) or the embryonic stem cell marker (OCT3/4). The obtained hUSCs could
be induced into osteogenic, adipogenic or chondrogenic differentiation. The hUSCs
from the children group showed higher proliferation and lower tendency to
senescence than those from the middle-aged and elder groups. After osteogenic
induction, the ALP activity and RUNX2 and OCN expression of hUSCs from the
children group were higher than those from the elder group. While no significant
differences were observed when comparing the middle-aged group with the children
group or the elder group. Donor age could influence the potency of hUSCs on
proliferation, senescence and capacity of osteogenic differentiation. hUSCs from
children group have shown higher proliferation, lower tendency to senescence, and
stronger osteogenic capacity, which means to be more suitable for basic research
and have better clinical application. Furthermore, hUSCs from all groups suggest
the application potential in bone tissue engineering as seed cells.
PMID- 28409293
TI - Defining the Need for Surgery in Small-Bowel Obstruction.
AB - BACKGROUND: Small-bowel obstruction is a frequent disorder in emergency medicine
and represents a major burden for patients and health care systems worldwide.
Within the past years, progress has been made regarding the management of small
bowel obstructions, including the use of contrast agent swallow as a tool in the
decision-making process. OBJECTIVES: This is a prospective controlled study
investigating the central role of contrast agent swallow in the diagnostic and
treatment algorithm for small-bowel obstruction at a university department of
surgery. Endpoints were the correct identification of patients who needed
operative treatment and the accuracy of a conservative treatment decision
including the analysis of dropout from this routine algorithm. METHODS: We
performed a single-center analysis of 181 consecutive patients diagnosed with a
small-bowel obstruction based on clinical, radiologic, and sonographic findings.
Patients with clinical signs of strangulation or peritonitis underwent immediate
surgery (group 1). Patients without signs of peritonitis and incomplete stop in
the initial abdominal plain film were considered eligible for Gastrografin(r)
challenge (group 2). RESULTS: Seventy-six of the 181 patients (42.0%) underwent
immediate surgery. A Gastrografin(r) challenge was initialized in 105 of the 181
patients (58.0%). Twenty of these 105 patients (19.1%) with persisting or
progressive symptoms and absence of contrast agent in the colon after 12 and 24 h
subsequently underwent surgery. Here, a segmental bowel resection was necessary
in 6 of these 20 patients (30.0%). In 16 out of 20 patients (80.0%) who failed
the Gastrografin(r) challenge, a corresponding correlate in terms of a
strangulation was detected intraoperatively. The Gastrografin(r) challenge had a
specificity of 96% and a sensitivity of 100%; accuracy to predict the need for
exploration was 96%. CONCLUSION: A straightforward algorithm based mainly on
contrast agent swallow for patients with small-bowel obstructions enabled a
timely and very accurate differentiation between patients qualifying for
conservative and operative treatment.
PMID- 28409294
TI - Self-management Following a Cardiac Event in People of Chinese Ethnicity Living
in Western Countries: A Scoping Review.
AB - Health outcomes and impact of cardiovascular disease vary between populations,
where ethnic minorities and immigrant groups are more likely to be disadvantaged.
Compared with the majority residents, health outcomes, especially short-term
mortality from coronary heart disease event are worse in people of Chinese
ethnicity, potentially due to poor self-management and experiences with the
healthcare system in host countries. A scoping review was conducted. Four
overarching themes were found: (1) understanding of heart disease, risk factors
and symptom recognition, (2) adherence to medication and lifestyle modification,
(3) health service/information choice, and (4) family role in disease self
management and decision making. All themes were greatly influenced by English
language proficiency and cultural practices. English language proficiency and
cultural practices should be taken into consideration when providing healthcare
services for people of Chinese ethnicity, as it plays an important role in self
management and experiences with the healthcare system.
PMID- 28409295
TI - Metal chelator TPEN selectively induces apoptosis in K562 cells through reactive
oxygen species signaling mechanism: implications for chronic myeloid leukemia.
AB - Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the
constitutive expression of BCR-ABL tyrosine kinase. Although successful
implementation of tyrosine kinase inhibitors for the treatment of CML remain a
traditional choice for molecularly targeted therapy, some patients present
primary or secondary resistance to such therapy. Therefore, alternative
therapeutic strategies are required to treat resistant CML cells. Accordingly,
new anti-proliferative and/or pro-apoptotic compounds would be needed for
clinical treatment. In the present investigation, we demonstrate that TPEN (e.g.
3 MUM), a lipid-soluble metal chelator, induces apoptosis in K562 cells via a
molecular cascade involving H2O2 ? JNK, NF-kappaB > c-JUN, P73 > PUMA, BAX > loss
of DeltaPsim > CASPASE-3 > nuclei/DNA fragmentation. Fragmentation of the nuclei
and DNA are indicative of cell death by apoptosis. Remarkably, the antioxidant N
acetyl-cysteine, and inhibitors of the transcription factors CASPASE 3 and (JNK)
kinase, decreased oxidative stress (OS) and cell death in these cells. This is
evidenced by fluorescence microscopy, flow cytometry and immunocytochemistry for
OS markers (e.g. generation of H2O2 and DJ 1 oxidation) and nuclear expression of
apoptotic markers (e.g. activated caspase 3 and JNK kinase). In addition, TPEN
causes no detectable damage in human peripheral blood lymphocyte cells (hPBLCs).
We conclude that TPEN selectively induces apoptosis in K562 cells via an OS
mechanism. Our findings may provide insight into more effective CML anticancer
therapies.
PMID- 28409296
TI - Silver(I) complexes with chromone-derived hydrazones: investigation on the
antimicrobial and cytotoxic effects.
AB - Complexes [Ag(HCrPh)2]NO3.2H2O (1) and [Ag(HCrpClPh)2]NO3 (2) were obtained with
3-formyl-6-methylchromone-phenyl hydrazone (HCrPh, HL1) and 3-formyl-6
methylchromone-para-chloro-phenyl hydrazone (HCrpClPh, HL2). Although the
hydrazones were inactive, upon coordination to silver(I) antifungal activity
significantly improved against several Candida strains. Complexes (1-2) revealed
to be more active than silver nitrate, silver sulfadiazine and the reference drug
nystatin against Candida parapsilosis. The cytotoxic activities of the hydrazones
and their silver(I) complexes were evaluated in comparison with cisplatin on
B16F10 (metastatic melanoma) and Melan-a (non-tumorigenic melanocyte) cells. The
hydrazones showed low cytotoxicity against B16F10 cells, reducing only about 20%
of cell viability at the concentration of 10 MUM. Upon coordination to silver(I)
the cytotoxic effect did not appreciably change in complex (1) while complex (2)
proved to be as cytotoxic as cisplatin and much more cytotoxic than both the free
ligand and silver nitrate at 1 MUM. Both complexes (1) and (2) were less active
than cisplatin on non-malignant Melan-a cells, indicating that these compounds
might promote less damage on normal cells.
PMID- 28409297
TI - The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in
patients submitted to elective surgeries.
AB - PURPOSE: Rocuronium (ROC) is a neuromuscular blocker mainly eliminated by biliary
excretion dependent on organic anion transporting polypeptide 1A2 (OATP1A2)
hepatocellular uptake. However, the influence of SLCO1A2 (gene encoding OATP1A2)
genetic polymorphism on ROC pharmacokinetics was never described before. The
objective of this work was to evaluate the influence of genetic polymorphisms of
SLCO1A2 on the pharmacokinetics of rocuronium (ROC). METHODS: Patients undergoing
elective surgeries under general anesthesia using rocuronium as a neuromuscular
blocker were genotyped for SLCO1A2 polymorphisms in the coding region (41A>G,
382A>T, 404A>T, 502C>T, 516A>C, 559G>A, 830C>A, and 833delA) and in the promoter
region (-1105G>A, -1032G>A, -715T>C, -361G>A, and -189_-188insA). Rocuronium
pharmacokinetic parameters were estimated by non-compartmental analysis. RESULTS:
None of the patients had heterozygous or homozygous variant of 404A>T, 382A>T,
502C>T, 833delA, 830C>A, 41A>G, and -715T>C. A linkage disequilibrium was found
between -1105G>A and -1032G>A genotypes. Patients genotyped as -A or AA (n = 17)
for SLCO1A2 -189_-188InsA showed reduced total clearance of ROC compared to
patients genotyped as -/- (n = 13) (151.6 vs 207.1 mL/min, p <= 0.05). The
pharmacokinetics parameters of ROC were not significantly different between other
SLCO1A2 genotypes. CONCLUSION: SLCO1A2 -189_-188InsA polymorphism is related to
the reduced clearance of rocuronium in patients submitted to elective surgeries
under general anesthesia. TRIAL REGISTRATION: NCT 02399397 ( ClinicalTrials.gov
).
PMID- 28409298
TI - Modeling Asymmetric Cell Division in Caulobacter crescentus Using a Boolean Logic
Approach.
AB - Caulobacter crescentus is a model organism for the study of asymmetric division
and cell type differentiation, as its cell division cycle generates a pair of
daughter cells that differ from one another in their morphology and behavior. One
of these cells (called stalked) develops a structure that allows it to attach to
solid surfaces and is the only one capable of dividing, while the other (called
swarmer) develops a flagellum that allows it to move in liquid media and divides
only after differentiating into a stalked cell type. Although many genes,
proteins, and other molecules involved in the asymmetric division exhibited by C.
crescentus have been discovered and characterized for several decades, it remains
as a challenging task to understand how cell properties arise from the high
number of interactions between these molecular components. This chapter describes
a modeling approach based on the Boolean logic framework that provides a means
for the integration of knowledge and study of the emergence of asymmetric
division. The text illustrates how the simulation of simple logic models gives
valuable insight into the dynamic behavior of the regulatory and signaling
networks driving the emergence of the phenotypes exhibited by C. crescentus.
These models provide useful tools for the characterization and analysis of other
complex biological networks.
PMID- 28409299
TI - Spatiotemporal Models of the Asymmetric Division Cycle of Caulobacter crescentus.
AB - The spatial localization of proteins within the cytoplasm of bacteria is an
underappreciated but critical aspect of cell cycle regulation for many
prokaryotes. In Caulobacter crescentus-a model organism for the study of
asymmetric cell reproduction in prokaryotes-heterogeneous localization of
proteins has been identified as the underlying cause of asymmetry in cell
morphology, DNA replication, and cell division. However, significant questions
remain. Firstly, the mechanisms by which proteins localize in the organelle-free
prokaryotic cytoplasm remain obscure. Furthermore, how variations in the spatial
and temporal dynamics of cell fate determinants regulate signaling pathways and
orchestrate the complex programs of asymmetric cell division and differentiation
are subjects of ongoing research. In this chapter, we review current efforts in
investigating these two questions. We describe how mathematical models of
spatiotemporal protein dynamics are being used to generate and test competing
hypotheses and provide complementary insight about the control mechanisms that
regulate asymmetry in protein localization and cell division.
PMID- 28409300
TI - Intrinsic and Extrinsic Determinants Linking Spindle Pole Fate, Spindle Polarity,
and Asymmetric Cell Division in the Budding Yeast S. cerevisiae.
AB - The budding yeast S. cerevisiae is a powerful model to understand the multiple
layers of control driving an asymmetric cell division. In budding yeast,
asymmetric targeting of the spindle poles to the mother and bud cell compartments
respectively orients the mitotic spindle along the mother-bud axis. This program
exploits an intrinsic functional asymmetry arising from the age distinction
between the spindle poles-one inherited from the preceding division and the other
newly assembled. Extrinsic mechanisms convert this age distinction into
differential fate. Execution of this program couples spindle orientation with the
segregation of the older spindle pole to the bud. Remarkably, similar stereotyped
patterns of inheritance occur in self-renewing stem cell divisions underscoring
the general importance of studying spindle polarity and differential fate in
yeast. Here, we review the mechanisms accounting for this pivotal interplay
between intrinsic and extrinsic asymmetries that translate spindle pole age into
differential fate.
PMID- 28409302
TI - Asymmetric Cell Division in the One-Cell C. elegans Embryo: Multiple Steps to
Generate Cell Size Asymmetry.
AB - The first division of the one-cell C. elegans embryo has been a fundamental model
in deciphering the mechanisms underlying asymmetric cell division. Polarization
of the one-cell zygote is induced by a signal from the sperm centrosome and
results in the asymmetric distribution of PAR proteins. Multiple mechanisms then
maintain PAR polarity until the end of the first division. Once asymmetrically
localized, PAR proteins control several essential aspects of asymmetric division,
including the position of the mitotic spindle along the polarity axis.
Coordination of the spindle and cytokinetic furrow positions is the next
essential step to ensure proper asymmetric division. In this chapter, I review
the different mechanisms underlying these successive steps of asymmetric
division. Work from the last 30 years has revealed the existence of multiple and
redundant regulatory pathways which ensure division robustness. Besides the
essential role of PAR proteins, this work also emphasizes the importance of both
microtubules and actomyosin throughout the different steps of asymmetric
division.
PMID- 28409303
TI - Size Matters: How C. elegans Asymmetric Divisions Regulate Apoptosis.
AB - Apoptosis is a form of programmed cell death used by metazoans to eliminate
abnormal cells, control cell number, and shape the development of organs. The use
of the nematode Caenorhabditis elegans as a model for the study of apoptosis has
led to important insights into how cells die and how their corpses are removed.
Eighty percent of these apoptotic cell deaths occur during nervous system
development and in daughters of neuroblasts that divide asymmetrically.
Pioneering work defined a conserved apoptosis pathway that is initiated in C.
elegans by the BH3-only protein EGL-1 and that leads to the activation of the
caspase CED-3. While the execution of the apoptotic fate is well understood, much
less is known about the mechanisms that specify the apoptotic fate of particular
cells. In some cells fated to die, this regulation occurs at the level of the egl
1 gene transcription, and investigators have identified several lineage-specific
transcription factors that both positively and negatively regulate egl-1. In this
review, we focus on a second set of molecules that appear to influence apoptosis
by controlling the position of the cleavage plane in divisions that produce
apoptotic cells.
PMID- 28409301
TI - Wnt Signaling Polarizes C. elegans Asymmetric Cell Divisions During Development.
AB - Asymmetric cell division is a common mode of cell differentiation during the
invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage,
and continuing throughout embryogenesis and larval development, mother cells are
polarized by Wnt ligands, causing an asymmetric inheritance of key members of a
Wnt/beta-catenin signal transduction pathway termed the Wnt/beta-catenin
asymmetry pathway. The resulting daughter cells are distinct at birth with one
daughter cell activating Wnt target gene expression via beta-catenin activation
of TCF, while the other daughter displays transcriptional repression of these
target genes. Here, we seek to review the body of evidence underlying a unified
model for Wnt-driven asymmetric cell division in C. elegans, identify global
themes that occur during asymmetric cell division, as well as highlight tissue
specific variations. We also discuss outstanding questions that remain unanswered
regarding this intriguing mode of asymmetric cell division.
PMID- 28409304
TI - The Midbody and its Remnant in Cell Polarization and Asymmetric Cell Division.
AB - The midbody is a protein-dense assembly that forms during cytokinesis when the
actomyosin ring constricts around bundling central spindle microtubules. After
its initial description by Walther Flemming in the late nineteenth century and
its rediscovery through electron microscopy in the 1960s and 1970s, its
ultrastructural organization and the sequential recruitment of its molecular
constituents has only been elucidated in the past decade. Recently, it has become
clear that the midbody can serve as a polarity cue during asymmetric cell
division, cell polarization, and spindle orientation by coordinating cytoskeletal
organization, vesicular transport, and localized cortical cues. In this chapter,
these newly emerging functions will be discussed as well as asymmetries during
midbody formation and their consequences for cellular organization in tissues.
PMID- 28409305
TI - Drosophila melanogaster Neuroblasts: A Model for Asymmetric Stem Cell Divisions.
AB - Asymmetric cell division (ACD) is a fundamental mechanism to generate cell
diversity, giving rise to daughter cells with different developmental potentials.
ACD is manifested in the asymmetric segregation of proteins or mRNAs, when the
two daughter cells differ in size or are endowed with different potentials to
differentiate into a particular cell type (Horvitz and Herskowitz, Cell 68:237
255, 1992). Drosophila neuroblasts, the neural stem cells of the developing fly
brain, are an ideal system to study ACD since this system encompasses all of
these characteristics. Neuroblasts are intrinsically polarized cells, utilizing
polarity cues to orient the mitotic spindle, segregate cell fate determinants
asymmetrically, and regulate spindle geometry and physical asymmetry. The
neuroblast system has contributed significantly to the elucidation of the basic
molecular mechanisms underlying ACD. Recent findings also highlight its
usefulness to study basic aspects of stem cell biology and tumor formation. In
this review, we will focus on what has been learned about the basic mechanisms
underlying ACD in fly neuroblasts.
PMID- 28409306
TI - Asymmetric Divisions in Oogenesis.
AB - In the majority of animals, the oocyte/egg is structurally, molecularly, and
functionally asymmetric. Such asymmetry is a prerequisite for a flawless
fertilization and faithful segregation of maternal determinants during subsequent
embryonic development. The oocyte asymmetry develops during oogenesis and must be
maintained during consecutive and obligatorily asymmetric oogonial divisions,
which depending on the species lead to the formation of either oocyte alone or
oocyte and nurse cell complex. In the following chapter, we summarize current
knowledge on the asymmetric oogonial divisions in invertebrate (insects) and
vertebrate (Xenopus) species.
PMID- 28409307
TI - Asymmetric Localization and Distribution of Factors Determining Cell Fate During
Early Development of Xenopus laevis.
AB - Asymmetric division is a property of eukaryotic cells that is fundamental to the
formation of higher life forms. Despite its importance, the mechanism behind it
remains elusive. Asymmetry in the cell is induced by polarization of cell fate
determinants that become unevenly distributed among progeny cells. So far dozens
of determinants have been identified. Xenopus laevis is an ideal system to study
asymmetric cell division during early development, because of the huge size of
its oocytes and early-stage blastomeres. Here, we present the current knowledge
about localization and distribution of cell fate determinants along the three
body axes: animal-vegetal, dorsal-ventral, and left-right. Uneven distribution of
cell fate determinants during early development specifies the formation of the
embryonic body plan.
PMID- 28409308
TI - Asymmetries in Cell Division, Cell Size, and Furrowing in the Xenopus laevis
Embryo.
AB - Asymmetric cell divisions produce two daughter cells with distinct fate. During
embryogenesis, this mechanism is fundamental to build tissues and organs because
it generates cell diversity. In adults, it remains crucial to maintain stem
cells. The enthusiasm for asymmetric cell division is not only motivated by the
beauty of the mechanism and the fundamental questions it raises, but has also
very pragmatic reasons. Indeed, misregulation of asymmetric cell divisions is
believed to have dramatic consequences potentially leading to pathogenesis such
as cancers. In diverse model organisms, asymmetric cell divisions result in two
daughter cells, which differ not only by their fate but also in size. This is the
case for the early Xenopus laevis embryo, in which the two first embryonic
divisions are perpendicular to each other and generate two pairs of blastomeres,
which usually differ in size: one pair of blastomeres is smaller than the other.
Small blastomeres will produce embryonic dorsal structures, whereas the larger
pair will evolve into ventral structures. Here, we present a speculative model on
the origin of the asymmetry of this cell division in the Xenopus embryo. We also
discuss the apparently coincident asymmetric distribution of cell fate
determinants and cell-size asymmetry of the 4-cell stage embryo. Finally, we
discuss the asymmetric furrowing during epithelial cell cytokinesis occurring
later during Xenopus laevis embryo development.
PMID- 28409309
TI - Asymmetric and Unequal Cell Divisions in Ascidian Embryos.
AB - Asymmetric cell division during embryogenesis contributes to cell diversity by
generating daughter cells that adopt distinct developmental fates. In this
chapter, we summarize current knowledge of three examples of asymmetric cell
division occurring in ascidian early embryos: (1) Three successive cell divisions
that are asymmetric in terms of cell fate and unequal in cell size in the
germline lineage at the embryo posterior pole. A subcellular structure, the
centrosome-attracting body (CAB), and maternal PEM mRNAs localized within it
control both the positioning of the cell division planes and segregation of the
germ cell fates. (2) Asymmetric cell divisions involving endoderm and mesoderm
germ layer separation. Asymmetric partitioning of zygotically expressed mRNA for
Not, a homeodomain transcription factor, promotes the mesoderm fate and
suppresses the endoderm fate. This asymmetric partitioning is mediated by
transient nuclear migration toward the mesodermal pole of the mother cell, where
the mRNA is delivered. In this case, there is no special regulation of cleavage
plane orientation. (3) Asymmetric cell divisions in the marginal region of the
vegetal hemisphere. The directed extracellular FGF and ephrin signals polarize
the mother cells, inducing distinct fates in a pair of daughter cells (nerve
versus notochord and mesenchyme versus muscle). The directions of cell division
are regulated and oriented but independently of FGF and ephrin signaling. In
these examples, polarization of the mother cells is facilitated by localized
maternal factors, by delivery of transcripts from the nucleus to one pole of each
cell, and by directed extracellular signals. Two cellular processes-asymmetric
fate allocation and orientation of the cell division plane-are coupled by a
single factor in the first example, but these processes are regulated
independently in the third example. Thus, various modes of asymmetric cell
division operate even at the early developmental stages in this single type of
organism.
PMID- 28409311
TI - Symmetry Does not Come for Free: Cellular Mechanisms to Achieve a Symmetric Cell
Division.
AB - During mitosis cells can divide symmetrically to proliferate or asymmetrically to
generate tissue diversity. While the mechanisms that ensure asymmetric cell
division have been extensively studied, it is often assumed that a symmetric cell
division is the default outcome of mitosis. Recent studies, however, imply that
the symmetric nature of cell division is actively controlled, as they reveal
numerous mechanisms that ensure the formation of equal-sized daughter cells as
cells progress through cell division. Here we review our current knowledge of
these mechanisms and highlight possible key questions in the field.
PMID- 28409310
TI - Asymmetries and Symmetries in the Mouse Oocyte and Zygote.
AB - Mammalian oocytes grow periodically after puberty thanks to the dialogue with
their niche in the follicle. This communication between somatic and germ cells
promotes the accumulation, inside the oocyte, of maternal RNAs, proteins and
other molecules that will sustain the two gamete divisions and early embryo
development up to its implantation. In order to preserve their stock of maternal
products, oocytes from all species divide twice minimizing the volume of their
daughter cells to their own benefit. For this, they undergo asymmetric divisions
in size where one main objective is to locate the division spindle with its
chromosomes off-centred. In this chapter, we will review how this main objective
is reached with an emphasis on the role of actin microfilaments in this process
in mouse oocytes, the most studied example in mammals. This chapter is subdivided
into three parts: I-General features of asymmetric divisions in mouse oocytes, II
Mechanism of chromosome positioning by actin in mouse oocytes and III-Switch from
asymmetric to symmetric division at the oocyte-to-embryo transition.
PMID- 28409312
TI - A Comparative Perspective on Wnt/beta-Catenin Signalling in Cell Fate
Determination.
AB - The Wnt/beta-catenin pathway is an ancient and highly conserved signalling
pathway that plays fundamental roles in the regulation of embryonic development
and adult homeostasis. This pathway has been implicated in numerous cellular
processes, including cell proliferation, differentiation, migration,
morphological changes and apoptosis. In this chapter, we aim to illustrate with
specific examples the involvement of Wnt/beta-catenin signalling in cell fate
determination. We discuss the roles of the Wnt/beta-catenin pathway in specifying
cell fate throughout evolution, how its function in patterning during development
is often reactivated during regeneration and how perturbation of this pathway has
negative consequences for the control of cell fate.The origin of all life was a
single cell that had the capacity to respond to cues from the environment. With
evolution, multicellular organisms emerged, and as a result, subsets of cells
arose to form tissues able to respond to specific instructive signals and perform
specialised functions. This complexity and specialisation required two types of
messages to direct cell fate: intra- and intercellular. A fundamental question in
developmental biology is to understand the underlying mechanisms of cell fate
choice. Amongst the numerous external cues involved in the generation of cellular
diversity, a prominent pathway is the Wnt signalling pathway in all its forms.
PMID- 28409314
TI - Regulation of Asymmetric Cell Division in Mammalian Neural Stem and Cancer
Precursor Cells.
AB - Stem and progenitor cells are characterized by their abilities to self-renew and
produce differentiated progeny. The balance between self-renewal and
differentiation is achieved through control of cell division mode, which can be
either asymmetric or symmetric. Failure to properly control cell division mode
may result in premature depletion of the stem/progenitor cell pool or abnormal
growth and impaired differentiation. In many tissues, including the brain, stem
cells and progenitor cells undergo asymmetric cell division through the
establishment of cell polarity. Cell polarity proteins are therefore potentially
critical regulators of asymmetric cell division. Decrease or loss of asymmetric
cell division can be associated with reduced differentiation common during aging
or impaired remyelination as seen in demyelinating diseases. Progenitor-like
glioma precursor cells show decreased asymmetric cell division rates and
increased symmetric divisions, which suggests that asymmetric cell division
suppresses brain tumor formation. Cancer stem cells, on the other hand, still
undergo low rates of asymmetric cell division, which may provide them with a
survival advantage during therapy. These findings led to the hypotheses that
asymmetric cell divisions are not always tumor suppressive but can also be
utilized to maintain a cancer stem cell population. Proper control of cell
division mode is therefore not only deemed necessary to generate cellular
diversity during development and to maintain adult tissue homeostasis but may
also prevent disease and determine disease progression. Since brain cancer is
most common in the adult and aging population, we review here the current
knowledge on molecular mechanisms that regulate asymmetric cell divisions in the
neural and oligodendroglial lineage during development and in the adult brain.
PMID- 28409313
TI - Extracellular Regulation of the Mitotic Spindle and Fate Determinants Driving
Asymmetric Cell Division.
AB - Stem cells use mode of cell division, symmetric (SCD) versus asymmetric (ACD), to
balance expansion with self-renewal and the generation of daughter cells with
different cell fates. Studies in model organisms have identified intrinsic
mechanisms that govern this process, which involves partitioning molecular
components between daughter cells, frequently through the regulation of the
mitotic spindle. Research performed in vertebrate tissues is revealing both
conservation of these intrinsic mechanisms and crucial roles for extrinsic cues
in regulating the frequency of these divisions. Morphogens and positional cues,
including planar cell polarity proteins and guidance molecules, regulate key
signaling pathways required to organize cell/ECM contacts and spindle pole
dynamics. Noncanonical WNT7A/VANGL2 signaling governs asymmetric cell division
and the acquisition of cell fates through spindle pole orientation in satellite
stem cells of regenerating muscle fibers. During cortical neurogenesis, the same
pathway regulates glial cell fate determination by regulating spindle size,
independent of its orientation. Sonic hedgehog (SHH) stimulates the symmetric
expansion of cortical stem and cerebellar progenitor cells and contributes to
cell fate acquisition in collaboration with Notch and Wnt signaling pathways.
SLIT2 also contributes to stem cell homeostasis by restricting ACD frequency
through the regulation of spindle orientation. The capacity to influence stem
cells makes these secreted factors excellent targets for therapeutic strategies
designed to enhance cell populations in degenerative disease or restrict cell
proliferation in different types of cancers.
PMID- 28409315
TI - Molecular Programs Underlying Asymmetric Stem Cell Division and Their Disruption
in Malignancy.
AB - Asymmetric division of stem cells is a highly conserved and tightly regulated
process by which a single stem cell produces two unequal daughter cells. One
retains its stem cell identity while the other becomes specialized through a
differentiation program and loses stem cell properties. Coordinating these events
requires control over numerous intra- and extracellular biological processes and
signaling networks. In the initial stages, critical events include the
compartmentalization of fate determining proteins within the mother cell and
their subsequent passage to the appropriate daughter cell in order to direct
their destiny. Disturbance of these events results in an altered dynamic of self
renewing and differentiation within the cell population, which is highly relevant
to the growth and progression of cancer. Other critical events include proper
asymmetric spindle assembly, extrinsic regulation through micro-environmental
cues, and non-canonical signaling networks that impact cell division and fate
determination. In this review, we discuss mechanisms that maintain the delicate
balance of asymmetric cell division in normal tissues and describe the current
understanding how some of these mechanisms are deregulated in cancer.
PMID- 28409316
TI - Mental foramen and lingual vascular canals of mandible on MDCT images: anatomical
study and review of the literature.
AB - The mental foramen and lingual vascular canals are related to vessels and nerves
in the mandibular body. The aim of the present study was to determine the number
and location of these structures and to make measurements of them. The archived
Multidetector Computed Tomography images of 100 adult (15- to 70-year-old)
patients were evaluated retrospectively. The diameters of the mental foramens and
their distances from the front, back, upper and lower reference points were
measured. The distribution of mental foramens with respect to the teeth was also
researched. The presence of lingual vascular canals, and the number of median and
lateral canals was determined, and the length of the median lingual vascular
canals measured. All measurement parameters were analyzed by gender, side and age
group. Eleven patients demonstrated a total of 15 accessory mental foramen.
Median lingual vascular canals were observed in 100% of cases, with lateral
lingual vascular canals determined in 32%. Significant differences were observed
in the results of different gender groups (P < 0.05); in contrast, no significant
difference was observed related with age or side. Accessory mental foramen was
determined mostly in males, and unilaterally on the right side; also, the
distances of mental foramen, except the distance from the back border of the
mandible (P < 0.05), were found to be higher, bilaterally, in males. Variation of
mental foramen, as well as the presence, position and size of lingual vascular
canals can be clearly investigated by multidetector computed tomography. A
preoperative knowledge of the positions of neurovascular and bone structures is
very important for preventing complications that may occur during or after
operations.
PMID- 28409317
TI - Predictors of Accommodation Among Families Affected by Fear-Based Disorders.
AB - Symptom accommodation-behaviors that family members engage in either to prevent
or alleviate a loved one's anxiety-is ubiquitous in families with relatives
affected by fear-based disorders (FBDs), yet little research has examined the
extent to which certain psychological factors predict symptom accommodation. The
current study examined several potential predictors (e.g., empathic concern)
among co-residing relatives of individuals diagnosed with FBDs. Participants (n =
53) completed a series of clinical interviews and self report measures. Results
indicated that accommodation occurred to similar degrees across relatives with
various relationships to the individual with a FBD, as well as across different
FBDs. Further, the predictors jointly explained a significant amount of variance
in accommodation; although, no single construct emerged as a unique predictor.
Empathic concern and expressed emotion emerged as marginally significant
predictors of symptom accommodation. Conclusions, limitations, and future
directions are discussed.
PMID- 28409318
TI - Incidental Learning of Gender Agreement in L2.
AB - Incidental learning of grammar has been an area of interest for many decades;
nevertheless, existing research has primarily focused on artificial or semi
artificial languages. The present study examines the incidental acquisition of
the grammar of a natural language by exposing adult speakers of an ungendered L1
(English) to the gender agreement patterns in Russian (a language that was novel
to the learners). Both receptive and productive knowledge and the mediating role
of working memory (WM) in learning were measured. Speakers of the ungendered
language were able to successfully acquire receptive but not productive
grammatical knowledge in a new language under incidental exposure. WM was engaged
in production but not in a grammaticality judgment task in the incidental
learning condition, indicating cognitive effort during knowledge retrieval.
PMID- 28409319
TI - The effect of gamma-enhancing binaural beats on the control of feature bindings.
AB - Binaural beats represent the auditory experience of an oscillating sound that
occurs when two sounds with neighboring frequencies are presented to one's left
and right ear separately. Binaural beats have been shown to impact information
processing via their putative role in increasing neural synchronization. Recent
studies of feature-repetition effects demonstrated interactions between
perceptual features and action-related features: repeating only some, but not all
features of a perception-action episode hinders performance. These partial
repetition (or binding) costs point to the existence of temporary episodic
bindings (event files) that are automatically retrieved by repeating at least one
of their features. Given that neural synchronization in the gamma band has been
associated with visual feature bindings, we investigated whether the impact of
binaural beats extends to the top-down control of feature bindings. Healthy
adults listened to gamma-frequency (40 Hz) binaural beats or to a constant tone
of 340 Hz (control condition) for ten minutes before and during a feature
repetition task. While the size of visuomotor binding costs (indicating the
binding of visual and action features) was unaffected by the binaural beats, the
size of visual feature binding costs (which refer to the binding between the two
visual features) was considerably smaller during gamma-frequency binaural beats
exposure than during the control condition. Our results suggest that binaural
beats enhance selectivity in updating episodic memory traces and further
strengthen the hypothesis that neural activity in the gamma band is critically
associated with the control of feature binding.
PMID- 28409320
TI - Vitamin D, sub-inflammation and insulin resistance. A window on a potential role
for the interaction between bone and glucose metabolism.
AB - Vitamin D is a key hormone involved in the regulation of calcium/phosphorous
balance and recently it has been implicated in the pathogenesis of sub
inflammation, insulin resistance and obesity. The two main forms of vitamin D are
cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form
(1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in
liver, kidney, pancreas and immune cells. Vitamin D increases the production of
some anti-inflammatory cytokines and reduces the release of some pro-inflammatory
cytokines. Low levels of Vitamin D are also associated with an up-regulation of
TLRs expression and a pro-inflammatory state. Regardless of the effect on
inflammation, Vitamin D seems to directly increase insulin sensitivity and
secretion, through different mechanisms. Considering the importance of low grade
chronic inflammation in metabolic syndrome, obesity and diabetes, many authors
hypothesized the involvement of this nutrient/hormone in the pathogenesis of
these diseases. Vitamin D status could alter the balance between pro and anti
inflammatory cytokines and thus affect insulin action, lipid metabolism and
adipose tissue function and structure. Numerous studies have shown that Vitamin D
concentrations are inversely associated with pro-inflammatory markers, insulin
resistance, glucose intolerance and obesity. Interestingly, some longitudinal
trials suggested also an inverse association between vitamin D status and
incident type 2 diabetes mellitus. However, vitamin D supplementation in humans
showed controversial effects: with some studies demonstrating improvements in
insulin sensitivity, glucose and lipid metabolism while others showing no
beneficial effect on glycemic control and on inflammation. In conclusion,
although the evidences of a significant role of Vitamin D on inflammation,
insulin resistance and insulin secretion in the pathogenesis of obesity,
metabolic syndrome and type 2 diabetes, its potential function in treatment and
prevention of type 2 diabetes mellitus is unclear. Encouraging results have
emerged from Vitamin D supplementation trials on patients at risk of developing
diabetes and further studies are needed to fully explore and understand its
clinical applications.
PMID- 28409321
TI - An integrative overview of the molecular and physiological responses of sugarcane
under drought conditions.
AB - Drought is the main abiotic stress constraining sugarcane production. However,
our limited understanding of the molecular mechanisms involved in the drought
stress responses of sugarcane impairs the development of new technologies to
increase sugarcane drought tolerance. Here, an integrated approach was performed
to reveal the molecular and physiological changes in two closely related
sugarcane cultivars, including the most extensively planted cultivar in Brazil
(cv. RB867515), in response to moderate (-0.5 MPa) and severe (-1 MPa) drought
stress at the transcriptional, translational, and posttranslational levels. The
results show common and cultivar exclusive changes in specific genes related to
photosynthesis, carbohydrate, amino acid, and phytohormone metabolism. The novel
phosphoproteomics and redox proteomic analysis revealed the importance of
posttranslational regulation mechanisms during sugarcane drought stress. The
shift to soluble sugar, secondary metabolite production, and activation of ROS
eliminating processes in response to drought tolerance were mechanisms exclusive
to cv. RB867515, helping to explain the better performance and higher production
of this cultivar under these stress conditions.
PMID- 28409322
TI - Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma:
rethinking cancer immunotherapy.
AB - The immune system regulates angiogenesis in cancer by way of both pro- and
antiangiogenic activities. A bidirectional link between angiogenesis and the
immune system has been clearly demonstrated. Most antiangiogenic molecules do not
inhibit only VEGF signaling pathways but also other pathways which may affect
immune system. Understanding of the role of these pathways in the regulation of
immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell
carcinoma (RCC) is an immunogenic tumor in which angiogenesis and
immunosuppression work hand in hand, and its growth is associated with impaired
antitumor immunity. Given the antitumor activity of selected TKIs in metastatic
RCC (mRCC), it seems relevant to assess their effect on the immune system. The
confirmation that TKIs improve cell cytokine response in mRCC provides a basis
for the rational combination and sequential treatment of TKIs and immunotherapy.
PMID- 28409323
TI - Differences in subtype distribution between screen-detected and symptomatic
invasive breast cancer and their impact on survival.
AB - PURPOSE: Stage shift is considered a major reason for more favorable outcomes in
patients with screen-detected breast cancer. However, even after adjusting for
clinical stage, unresolved issues concerning the reasons for a survival benefit
associated with screening programs remain. This study aims to evaluate
differences in subtype distribution and outcomes among patients with screen
detected and symptomatic invasive breast cancer and assess whether variations in
subtype distribution could explain differences in prognosis. METHODS: Survival
analysis was performed to estimate the likelihood of distant recurrence and death
in 1132 patients. Subtypes were defined as luminal A [estrogen receptor (ER)+
and/or progesterone receptor (PR)+, human epidermal growth factor receptor 2
(HER2)-, and Ki67 low], luminal B (HER2-) (ER+ and/or PR+, HER2-, and Ki67 high),
luminal B (HER2+) (ER+ and/or PR+ and HER2+), HER2 overexpressing (ER-, PR-, and
HER2+), and triple negative (ER-, PR-, and HER2-). RESULTS: Screen-detected
cancers had favorable clinicopathological characteristics, such as smaller tumor
size and a lower frequency of lymph node involvement. Women with screen-detected
cancers had a survival advantage. Subtype distribution differed significantly
among women with screen-detected and symptomatic cancer. Screen-detected cancers
were more likely to be luminal A and less likely to be HER2 overexpressing or
triple negative cancer compared with symptomatic cancers (luminal A 61.3 vs.
44.2%, HER2 overexpressing 4.0 vs. 8.0%, triple negative 8.0 vs. 15.9%). Node
status, mode of detection, and subtype were independent prognostic factors in the
multivariate analysis. CONCLUSIONS: Differences in subtype distribution between
screen-detected and symptomatic cancer could partially explain differences in
outcomes.
PMID- 28409324
TI - Generation and characterization of polyclonal and monoclonal antibodies to human
NTPDase2 including a blocking antibody.
AB - Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) is an ectonucleotidase
that modulates P2 receptor activation by hydrolyzing ATP to ADP. In rodents,
NTPDase2 is expressed by several specialized cell types such as vascular
adventitial cells, neuroglial cells, hepatic portal fibroblasts, gustatory type I
cells, and cells within the connective tissues of reproductive and
gastrointestinal organs. Much less is known regarding the expression and function
of NTPDase2 in humans. Here, we developed specific research tools to study human
NTPDase2. We generated mouse monoclonal antibodies and rabbit polyclonal
antibodies specific to human NTPDase2 and validated their specificity by western
blot, immunocytochemistry, immunohistochemistry, and flow cytometry. In addition,
one monoclonal antibody named hN2-D5 s specifically inhibits human NTPDase2
enzymatic activity but not mouse nor rat NTPDase2. Using these antibodies,
NTPDase2 immunoreactivity was detected on glial cells of the human enteric
nervous system suggesting a function of the enzyme in intestinal motility. In
conclusion, the new antibodies described in our work are novel tools that will
enhance future studies of NTPDase2 expression and function in humans.
PMID- 28409325
TI - Velocity Field Visualization in USP Dissolution Apparatus 3 Using Particle Image
Velocimetry.
AB - PURPOSE: The hydrodynamics in USP dissolution apparatus 3, at five different dip
rates, was characterized by analyzing phase-averaged velocity fields obtained
using Particle Image Velocimetry (PIV). METHODS: Phase locked 2 Component-PIV (2C
PIV) measurements were recorded on a typical dissolution apparatus 3
configuration with a black painted tablet fixed at the center of the bottom
porous screen of the reciprocating cylinder. A trigger mechanism was employed to
capture data over 12 phase positions for each reciprocation cycle. Data were
captured over a fixed number of cycles, based on dip rate, and the resultant
images were post-processed to obtain phase-averaged velocity fields at each
phase. RESULTS: For all dip rates studied, the sinusoidal nature of the
cylinder's reciprocating motion was evident in the images. The phase positions,
in which the cylinder was completely submerged, were characterized by
recirculation of liquid through the cylinder, top fitting cap, vessel-cylinder
annulus, and bottom fitting cap. The direction of recirculation was opposite for
phase positions during the up- and downstrokes. The end positions of the up- and
downstrokes were characterized by vortices below and above the cylinder
respectively. Increasing dip rates led mainly to increasing velocity magnitudes
while all flow characteristics, in general, were retained. CONCLUSIONS: The
hydrodynamics in typical USP dissolution apparatus 3 is characterized by cyclic
phase-dependent flow fields. Specifically, the velocity field distribution within
dissolution apparatus 3 is greatly influenced by the relative position of the top
cap to the liquid level in the cylinder.
PMID- 28409326
TI - Effect of corticision on orthodontic tooth movement in a rat model as assessed by
RNA sequencing.
AB - Corticision is a common technique to accelerate orthodontic tooth movement;
however, not much is known about the underlying mechanisms. In this study, we
investigated the mechanism of alveolar tissue remodeling after corticision in a
rat model of tooth movement (TM) by analyzing the differential transcriptome. A
total of 36 male rats were equally divided into TM and TM with corticision (TM+C)
groups. Alveolar bone response was examined using micro-computed tomography
(micro-CT). Osteoclasts and osteoblasts were quantified on tartrate-resistant
acid phosphatase (TRAP) and Goldner's trichrome staining. The transcriptomes of
alveolus around the left maxillary first molar were determined on RNA sequencing
(RNA-Seq), and the expression of selected differentially expressed genes (DEGs)
validated on quantitative reverse-transcriptase polymerase chain reaction (qRT
PCR). Immunohistochemical examination of alveolar tissue was performed to examine
the expressions of correlative proteins of the selected signaling pathway in the
TM and TM+C groups. The ratio of bone volume to total volume (BV/TV), and the
trabecular number (Tb.N) were significantly decreased, while the movement
distance and the trabecular separation (Tb.Sp) was significantly increased in the
TM+C group. However, no significant between-group difference in trabecular
thickness (Tb.Th) was observed. On histomorphometric analysis, a significant
increase in the number of osteoclasts and increased bone resorption was observed
in the TM+C group. A total of 399 DEGs were identified on RNA-SEq. Eleven
selected genes were confirmed on qRT-PCR, which included components of the Ras
signaling pathway. Four proteins of the Ras signaling pathway showed a higher
expression in the TM+C group. Our findings indicate that corticision may speed up
orthodontic tooth movement by accelerating osteoclastogenesis mediated via the
Ras signaling pathway.
PMID- 28409328
TI - Long-term treatment with bosutinib in a phase 1/2 study in Japanese chronic
myeloid leukemia patients resistant/intolerant to prior tyrosine kinase inhibitor
treatment.
AB - This long-term follow-up of a completed phase 1/2 study assessed the safety and
efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase
(CP) or advanced phase (ADV) chronic myeloid leukemia patients who were
resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment.
This analysis included 63 patients with a median bosutinib follow-up of 132 weeks
(range 3-372). In the CP second-line (2L) cohort, the cumulative major
cytogenetic response (MCyR) and major molecular response (MMR) rates throughout
the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the
cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively.
Of the eight ADV patients, MCyR was attained or maintained by 50% of patients,
and complete hematologic response was attained or maintained by 25% of patients.
Progression-free survival rate and overall survival rate at 96 weeks were,
respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV
patients. The most common adverse events (>50%) reported were diarrhea (95%),
nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy
and a manageable tolerability profile over long-term use in Japanese
patients.ClinicalTrials.gov: NCT00811070.
PMID- 28409329
TI - Purification of leukemic blast cells from blood smears using laser
microdissection.
AB - In treatment of acute myeloid leukemia (AML), prognostic factors, including gene
mutation and abnormal gene expression, enable risk stratification of patients.
However, in the case of a small proportion of leukemic blast cells, such as AML
associated with Down syndrome (AML-DS), it is not possible to examine prognostic
factors precisely due to the large proportion of normal cells. Here, we present a
novel method for examining prognostic factors by making a smear on a membrane
slide glass from a small amount of diagnostic specimen and collecting highly pure
leukemic blast cells by laser microdissection (LMD). We verified the
effectiveness of this method using 10% KPAM1 cell line suspension and peripheral
blood containing 20% blast cells obtained from a patient with transient abnormal
myelopoiesis (TAM). After making blood smears, approximately 100 cells were
collected and analyzed by direct sequencing. Frameshift mutations (2 bp deletion
and 17 bp duplication, respectively) in GATA-1 were detected in each sample,
suggesting KPAM1 and TAM blast cells were accurately purified. This novel method
enables us to precisely examine prognostic factors in many cases, even in cases
with a small proportion of leukemic blast cells or small specimens to preserve.
PMID- 28409330
TI - MicroRNA-192 regulates cell proliferation and cell cycle transition in acute
myeloid leukemia via interaction with CCNT2.
AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 18-22
nucleotides in length, which play an important role in malignant transformation.
The roles of miR-192 as an oncogene or tumor suppressor in solid tumors have been
previously reported. However, little is known about the role of miR-192 in human
acute myeloid leukemia. The results of the present study indicate that miR-192 is
significantly downregulated in specimens from acute myeloid leukemia patients.
Functional assays demonstrated that overexpression of miR-192 in NB4 and HL-60
cells significantly inhibited cell proliferation compared with that in control
cells, and induced G0/G1 cell cycle arrest, cell differentiation, and apoptosis
in vitro. Dual-luciferase reporter gene assays showed that miR-192 significantly
suppressed the activity of a reporter gene containing the wild type 3'-UTR of
CCNT2, but it did not suppress the activity of a reporter gene containing mutated
3'-UTR of CCNT2. QRT-PCR and Western blot assays showed that miR-192
significantly downregulated the expression of CCNT2 in human leukemia cells.
Exogenous expression of CCNT2 attenuated the cell cycle arrest induced by miR-192
in NB4 and HL-60 cells. Collectively, miR-192 inhibits cell proliferation and
induces G0/G1 cell cycle arrest in AML by regulating the expression of CCNT2.
PMID- 28409327
TI - Heat shock proteins and kidney disease: perspectives of HSP therapy.
AB - Heat shock proteins (HSPs) mediate a diverse range of cellular functions,
prominently including folding and regulatory processes of cellular repair. A
major property of these remarkable proteins, dependent on intracellular or
extracellular location, is their capacity for immunoregulation that optimizes
immune activity while avoiding hyperactivated inflammation. In this review,
recent investigations are described, which examine roles of HSPs in protection of
kidney tissue from various traumatic influences and demonstrate their potential
for clinical management of nephritic disease. The HSP70 class is particularly
attractive in this respect due to its multiple protective effects. The review
also summarizes current understanding of HSP bioactivity in the pathophysiology
of various kidney diseases, including acute kidney injury, diabetic nephropathy,
chronic glomerulonephritis, and lupus nephritis-along with other promising
strategies for their remediation, such as DNA vaccination.
PMID- 28409333
TI - The wearable defibrillator: a most affordable vest.
PMID- 28409331
TI - IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on
healthspan, pathology, and lifespan.
AB - Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging
mechanism that contributes to increased lifespan in diverse experimental models.
However, IGF-1 has also been shown to be essential for normal development and the
maintenance of tissue function late into the lifespan. These disparate findings
suggest that IGF-1 may be a pleiotropic modulator of health and aging, as
reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental
for another. We postulated that the effects of IGF-1 on tissue health and
function in advanced age are dependent on the tissue, the sex of the animal, and
the age at which IGF-1 is manipulated. In this study, we examined how alterations
in IGF-1 levels at multiple stages of development and aging influence overall
lifespan, healthspan, and pathology. Specifically, we investigated the effects of
perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and
viral approaches in both male and female igf f/f C57Bl/6 mice. Our results
support the concept that IGF-1 levels early during lifespan establish the
conditions necessary for subsequent healthspan and pathological changes that
contribute to aging. Nevertheless, these changes are specific for each sex and
tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human
studies) reduces cancer risk but does not increase lifespan. Overall, our results
indicate that the levels of IGF-1 during development influence late-life
pathology, suggesting that IGF-1 is a developmental driver of healthspan,
pathology, and lifespan.
PMID- 28409334
TI - Investigation of X-ray focal spot alignment using a jig of novel design.
AB - The X-ray focal spot and the centre of the flattening filter should be placed as
close as possible to the central axis (CAX) on a linear accelerator (linac) to
produce a radially symmetric beam. The aim of this study is to devise a method to
easily optimise the focal spot position of Varian linac photon beams generated
with a flattening filter. A simple and robust jig was designed and built to be
inserted into the largest electron applicator. Accessory and jaw position
interlocks were overridden to enable photon beam operation. The jig was made from
aluminium and consists of a plate permanently fixed inside a low melting point
alloy (LMPA) insert frame and a block machined to suspend an ion chamber below
the plate, such that the axis of the chamber is at the linac isocentre. The jig
was used to optimise the position of the X-ray beam focal spot with respect to
the device central axis (CAX). This was achieved by minimising the percentage
change in ionisation chamber signal between collimator rotations from 90 degrees
to 270 degrees as position steering was changed. As part of the investigation,
in-plane (radial) and cross-plane (transverse) profiles obtained from water
phantom scans were used to quantify how large the percentage ionisation change
can be before profiles are distorted in the region of the CAX.
PMID- 28409332
TI - A new mouse model of frailty: the Cu/Zn superoxide dismutase knockout mouse.
AB - Frailty is a geriatric syndrome that is an important public health problem for
the older adults living in the USA. Although several methods have been developed
to measure frailty in humans, we have very little understanding of its etiology.
Because the molecular basis of frailty is poorly understood, mouse models would
be of great value in determining which pathways contribute to the development of
frailty. More importantly, mouse models would be critical in testing potential
therapies to treat and possibly prevent frailty. In this article, we present data
showing that Sod1KO mice, which lack the antioxidant enzyme, Cu/Zn superoxide
dismutase, are an excellent model of frailty, and we compare the Sod1KO mice to
the only other mouse model of frailty, mice with the deletion of the IL-10 gene.
Sod1KO mice exhibit four characteristics that have been used to define human
frailty: weight loss, weakness, low physical activity, and exhaustion. In
addition, Sod1KO mice show increased inflammation and sarcopenia, which are
strongly associated with human frailty. The Sod1KO mice also show alterations in
pathways that have been proposed to play a role in the etiology of frailty:
oxidative stress, mitochondrial dysfunction, and cell senescence. Using Sod1KO
mice, we show that dietary restriction can delay/prevent characteristics of
frailty in mice.
PMID- 28409335
TI - Multichannel interictal spike activity detection using time-frequency entropy
measure.
AB - Localization of interictal spikes is an important clinical step in the pre
surgical assessment of pharmacoresistant epileptic patients. The manual selection
of interictal spike periods is cumbersome and involves a considerable amount of
analysis workload for the physician. The primary focus of this paper is to
automate the detection of interictal spikes for clinical applications in epilepsy
localization. The epilepsy localization procedure involves detection of spikes in
a multichannel EEG epoch. Therefore, a multichannel Time-Frequency (T-F) entropy
measure is proposed to extract features related to the interictal spike activity.
Least squares support vector machine is used to train the proposed feature to
classify the EEG epochs as either normal or interictal spike period. The proposed
T-F entropy measure, when validated with epilepsy dataset of 15 patients, shows
an interictal spike classification accuracy of 91.20%, sensitivity of 100% and
specificity of 84.23%. Moreover, the area under the curve of Receiver Operating
Characteristics plot of 0.9339 shows the superior classification performance of
the proposed T-F entropy measure. The results of this paper show a good spike
detection accuracy without any prior information about the spike morphology.
PMID- 28409337
TI - Surgical considerations with the operative fixation of unstable paediatric pelvic
ring injuries.
AB - INTRODUCTION: The operative treatment of unstable pelvic injuries in paediatrics
is not frequently indicated. The detailed modes of pelvic ring failure, surgical
techniques, fixation choices, and peri-operative difficulties are not well
reported. METHODS: From September 2010 to March 2016, 62 paediatric patients were
admitted to an academic level I trauma center with the diagnosis of pelvic ring
injury. Of them, 29 (17 males and 12 females) had operative fixation of unstable
pelvic injuries. Their average age was 11.7 +/- 4.4 years. RESULTS: There were
six Tile's B injuries and 23 type C injuries. The commonest modes of pelvic ring
failure were pubic rami fractures anteriorly and ligamentous sacroiliac joint
injuries posteriorly. The iliac apophysis was avulsed in nine patients. Supra
acetabular external fixators were frequently used for anterior fixation while
iliosacral IS screws and lateral compression LC screws were commonly used
posteriorly. Difficulties were encountered with open reduction and repair of
avulsed iliac apophyses in two patients. The IS screws pierced the soft iliac
wing in three patients. In two patients with open triradiate cartilage, the
purchase of retrograde LC screws was weak due the small sized crescent fragment.
CONCLUSION: The iliac apophysis needs to be repaired following reduction of the
displaced hemipelvis. Anterior supra-acetabular external fixation is a good
choice in paediatrics even with pubic symphysis diatasis as the pathology is
commonly a pubic apophysis avulsion. IS screws might be inserted through plates
to prevent piercing the soft iliac wing. Retrograde LC screws should be avoided
in young children.
PMID- 28409336
TI - Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid
Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue.
AB - Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease
inflammation and the incidence of chronic diseases including cardiovascular
disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake
increases the incidence of these conditions. Some health benefits of n-3 PUFA are
mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The
TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with
adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the
impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n
3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female
C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha
linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA,
and putative from CLA were quantified. CLA containing diets reduced AT mass by
~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA
and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA
derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F1alpha (P <
0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-,
DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived
alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA
derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and
PGF1alpha, PGF2alpha, and F2-isoprostanes. DHA counteracted CLA-induced effects
in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins,
respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased
anti-inflammatory oxylipins and diminished concentration of CLA-induced pro
inflammatory oxylipins in AT.
PMID- 28409338
TI - Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a
Residualizing Label and Preclinical Evaluation.
AB - PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain
antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as
trastuzumab, complicating its use for positron emission tomography (PET) imaging
of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds
to a different epitope on HER2 and thus might be a preferable vector for imaging
in these patients. The aim of this study was to evaluate the tumor targeting of F
18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts.
PROCEDURES: sdAb 2Rs15d was labeled with the residualizing labels N-succinimidyl
3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5
(guanidinomethyl)benzoate ([18F]RL-I) and N-succinimidyl 4-guanidinomethyl-3
[125I]iodobenzoate ([125I]SGMIB), and the purity and HER2-specific binding
affinity and immunoreactivity were assessed after labeling. The biodistribution
of I-125- and F-18-labeled 2Rs15d was determined in SCID mice bearing
subcutaneous BT474M1 xenografts. MicroPET/x-ray computed tomograph (CT) imaging
of [18F]RL-I-2Rs15d was performed in this model and compared to that of
nonspecific sdAb [18F]RL-I-R3B23. MicroPET/CT imaging was also done in an
intracranial HER2-positive breast cancer brain metastasis model after
administration of 2Rs15d-, 5F7-, and R3B23-[18F]RL-I conjugates. RESULTS: [18F]RL
I was conjugated to 2Rs15d in 40.8 +/- 9.1 % yield and with a radiochemical
purity of 97-100 %. Its immunoreactive fraction (IRF) and affinity for HER2
specific binding were 79.2 +/- 5.4 % and 7.1 +/- 0.4 nM, respectively.
[125I]SGMIB was conjugated to 2Rs15d in 58.4 +/- 8.2 % yield and with a
radiochemical purity of 95-99 %; its IRF and affinity for HER2-specific binding
were 79.0 +/- 12.9 % and 4.5 +/- 0.8 nM, respectively. Internalized radioactivity
in BT474M1 cells in vitro for [18F]RL-I-2Rs15d was 43.7 +/- 3.6, 36.5 +/- 2.6,
and 21.7 +/- 1.2 % of initially bound radioactivity at 1, 2, and 4 h,
respectively, and was similar to that seen for [125I]SGMIB-2Rs15d. Uptake of
[18F]RL-I-2Rs15d in subcutaneous xenografts was 16-20 %ID/g over 1-3 h.
Subcutaneous tumor could be clearly delineated by microPET/CT imaging with
[18F]RL-I-2Rs15d but not with [18F]RL-I-R3B23. Intracranial breast cancer brain
metastases could be visualized after intravenous administration of both [18F]RL-I
2Rs15d and [18F]RL-I-5F7. CONCLUSIONS: Although radiolabeled 2Rs15d conjugates
exhibited lower tumor cell retention both in vitro and in vivo than that observed
previously for 5F7, given that it binds to a different epitope on HER2 from those
targeted by the clinically utilized HER2-targeted therapeutic antibodies
trastuzumab and pertuzumab, F-18-labeled 2Rs15d has potential for assessing HER2
status by PET imaging after trastuzumab and/or pertuzumab therapy.
PMID- 28409340
TI - Drosophila Malpighian Tubules: A Model for Understanding Kidney Development,
Function, and Disease.
AB - The Malpighian tubules of insects are structurally simple but functionally
important organs, and their integrity is important for the normal excretory
process. They are functional analogs of human kidneys which are important
physiological organs as they maintain water and electrolyte balance in the blood
and simultaneously help the body to get rid of waste and toxic products after
various metabolic activities. In addition, it receives early indications of
insults to the body such as immune challenge and other toxic components and is
essential for sustaining life. According to National Vital Statistics Reports
2016, renal dysfunction has been ranked as the ninth most abundant cause of death
in the USA. This chapter provides detailed descriptions of Drosophila Malpighian
tubule development, physiology, immune function and also presents evidences that
Malpighian tubules can be used as a model organ system to address the fundamental
questions in developmental and functional disorders of the kidney.
PMID- 28409339
TI - Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with
[18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen
Measurements.
AB - PURPOSE: The purpose of this study is to use dynamic [18F]fluoromisonidazole
([18F]FMISO) positron emission tomography (PET) to compare estimates of tumor
hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood
ratios (TBR), and independent oxygen (pO2) measurements. PROCEDURES: BALB/c mice
with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO2
measurements. Data from 120-min dynamic [18F]FMISO scans were fit to two
compartment irreversible three rate constant (K 1, k 2, k 3) and Patlak models (K
i). Tumor HFs were calculated and compared using K i, k 3, TBR, and pO2 values.
The clinical impact of each method was evaluated on [18F]FMISO scans for three
non-small cell lung cancer (NSCLC) radiotherapy patients. RESULTS: HFs defined by
TBR (>=1.2, >=1.3, and >=1.4) ranged from 2 to 85 % of absolute tumor volume. HFs
defined by K i (>0.004 ml min cm-3) and k 3 (>0.008 min-1) varied from 9 to 85 %.
HF quantification was highly dependent on metric (TBR, k 3, or K i) and
threshold. HFs quantified on human [18F]FMISO scans varied from 38 to 67, 0 to
14, and 0.1 to 27 %, for each patient, respectively, using TBR, k 3, and K i
metrics. CONCLUSIONS: [18F]FMISO PET imaging metric choice and threshold impacts
hypoxia quantification reliability. Our results suggest that tracer kinetic
modeling has the potential to improve hypoxia quantification clinically as it may
provide a stronger correlation with direct pO2 measurements.
PMID- 28409341
TI - Zebrafish Pronephros Development.
AB - The pronephros is the first kidney type to form in vertebrate embryos. The first
step of pronephrogenesis in the zebrafish is the formation of the intermediate
mesoderm during gastrulation, which occurs in response to secreted morphogens
such as BMPs and Nodals. Patterning of the intermediate mesoderm into proximal
and distal cell fates is induced by retinoic acid signaling with downstream
transcription factors including wt1a, pax2a, pax8, hnf1b, sim1a, mecom, and
irx3b. In the anterior intermediate mesoderm, progenitors of the glomerular blood
filter migrate and fuse at the midline and recruit a blood supply. More
posteriorly localized tubule progenitors undergo epithelialization and fuse with
the cloaca. The Notch signaling pathway regulates the formation of multi-ciliated
cells in the tubules and these cells help propel the filtrate to the cloaca. The
lumenal sheer stress caused by flow down the tubule activates anterior collective
migration of the proximal tubules and induces stretching and proliferation of the
more distal segments. Ultimately these processes create a simple two-nephron
kidney that is capable of reabsorbing and secreting solutes and expelling excess
water-processes that are critical to the homeostasis of the body fluids. The
zebrafish pronephric kidney provides a simple, yet powerful, model system to
better understand the conserved molecular and cellular progresses that drive
nephron formation, structure, and function.
PMID- 28409342
TI - Zebrafish as a Model of Kidney Disease.
AB - Animal models have been an invaluable means to advance biomedical research as
they provide experimental avenues for cellular and molecular investigations of
disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian
models that can be used to apply powerful genetic experimental methods normally
used in invertebrates to answer questions about vertebrate development and
disease. In the case of the kidney, the zebrafish has proven itself to be an
applicable and versatile experimental system, mainly due to the simplicity of its
pronephros, which contains two nephrons that possess conserved structural and
physiological aspects with mammalian nephrons. Numerous genes that were not
previously related to kidney conditions have now been linked to renal diseases by
applying genetic screening with the zebrafish. In fact, a large collection of
mutations that affect nephron formation and function were generated through
phenotype-based forward screens. Complementary reverse genetic approaches have
also been insightful, with methods spanning the use of antisense morpholino
oligonucleotides to genome editing approaches such as the CRISPR/Cas9 system, to
selectively knock down or knock out genes of interest to see if they produce
kidney phenotypes. Acute kidney injury (AKI) has also been easily modeled in the
zebrafish by injecting nephrotoxins, directly inducing damage through surgical
intervention, or by generating transgenic lines that express compounds in a
tissue-specific manner that when exposed to certain drugs promote an apoptotic
response within cells. In this chapter, we provide an overview of these various
approaches as well as discuss many of the contributions that have been achieved
through the use of zebrafish to model kidney disease.
PMID- 28409343
TI - Use of Xenopus Frogs to Study Renal Development/Repair.
AB - The Xenopus genus includes several members of aquatic frogs native to Africa but
is perhaps best known for the species Xenopus laevis and Xenopus tropicalis.
These species were popularized as model organisms from as early as the 1800s and
have been instrumental in expanding several biological fields including cell
biology, environmental toxicology, regenerative biology, and developmental
biology. In fact, much of what we know about the formation and maturation of the
vertebrate renal system has been acquired by examining the intricate genetic and
morphological patterns that epitomize nephrogenesis in Xenopus. From these
numerous reports, we have learned that the process of kidney development is as
unique among organs as it is conserved among vertebrates. While development of
most organs involves increases in size at a single location, development of the
kidney occurs through a series of three increasingly complex nephric structures
that are temporally distinct from one another and which occupy discrete spatial
locales within the body. These three renal systems all serve to provide
homeostatic, osmoregulatory, and excretory functions in animals. Importantly, the
kidneys in amphibians, such as Xenopus, are less complex and more easily accessed
than those in mammals, and thus tadpoles and frogs provide useful models for
understanding our own kidney development. Several descriptive and mechanistic
studies conducted with the Xenopus model system have allowed us to elucidate the
cellular and molecular mediators of renal patterning and have also laid the
foundation for our current understanding of kidney repair mechanisms in
vertebrates. While some species-specific responses to renal injury have been
observed, we still recognize the advantage of the Xenopus system due to its
distinctive similarity to mammalian wound healing, reparative, and regenerative
responses. In addition, the first evidence of renal regeneration in an amphibian
system was recently demonstrated in Xenopus laevis. As genetic and molecular
tools continue to advance, our appreciation for and utilization of this amphibian
model organism can only intensify and will certainly provide ample opportunities
to further our understanding of renal development and repair.
PMID- 28409344
TI - Tissue-Specific Functions of p53 During Kidney Development.
AB - p53 is best identified as a tumor suppressor for its transcriptional control of
genes involved in cell cycle progression and apoptosis. Beyond its irrefutable
involvement in restraining unchecked cell proliferation, research over the past
several years has indicated a requirement for p53 function in sustaining normal
development. Here I summarize the role of p53 in embryonic development, with a
focus on knowledge gained from p53 loss and overexpression during kidney
development. In contrast to its classical role in suppressing proliferative
pathways, p53 positively regulates nephron progenitor cell (NPC) renewal.
Emerging evidence suggests p53 may control cell fate decisions by preserving
energy metabolism homeostasis of progenitors in the nephrogenic niche.
Maintaining a critical level of p53 function appears to be a prerequisite for
optimal nephron endowment. Defining the molecular networks targeted by p53 in the
NPC may well provide new targets not only for regenerative medicine but also for
cancer treatment.
PMID- 28409345
TI - Growth Factor Regulation in the Nephrogenic Zone of the Developing Kidney.
AB - New nephrons are induced by the interaction between mesenchymal progenitor cells
and collecting duct tips, both of which are located at the outer edge of the
kidney. This leading edge of active nephron induction is known as the nephrogenic
zone. Cell populations found within this zone include collecting duct tips, cap
mesenchyme cells, pretubular aggregates, nephrogenic zone interstitium,
hemoendothelial progenitor cells, and macrophages. The close association of these
dynamic progenitor cell compartments enables the intricate and synchronized
patterning of the epithelial and the vascular components of the nephron.
Understanding signaling interactions between the distinct progenitor cells of the
nephrogenic zone are essential to determining the basis for new nephron
formation, an important goal in regenerative medicine. A variety of technologies
have been applied to define essential signaling pathways, including organ
culture, mouse genetics, and primary cell culture. This chapter provides an
overview of essential signaling pathways and discusses how these may be
integrated.
PMID- 28409346
TI - Development and Diseases of the Collecting Duct System.
AB - The collecting duct of the mammalian kidney is important for the regulation of
extracellular volume, osmolarity, and pH. There are two major structurally and
functionally distinct cell types: principal cells and intercalated cells. The
former regulates Na+ and water homeostasis, while the latter participates in acid
base homeostasis. In vivo lineage tracing using Cre recombinase or its
derivatives such as CreGFP and CreERT2 is a powerful new technique to identify
stem/progenitor cells in their native environment and to decipher the origins of
the tissue that they give rise to. Recent studies using this technique in mice
have revealed multiple renal progenitor cell populations that differentiate into
various nephron segments and collecting duct. In particular, emerging evidence
suggests that like principal cells, most of intercalated cells originate from the
progenitor cells expressing water channel Aquaporin 2. Mutations or malfunctions
of the channels, pumps, and transporters expressed in the collecting duct system
cause various human diseases. For example, gain-of-function mutations in ENaC
cause Liddle's syndrome, while loss-of-function mutations in ENaC lead to
Pseudohypoaldosteronism type 1. Mutations in either AE1 or V-ATPase B1 result in
distal renal tubular acidosis. Patients with disrupted AQP2 or AVPR2 develop
nephrogenic diabetes insipidus. A better understanding of the function and
development of the collecting duct system may facilitate the discovery of new
therapeutic strategies for treating kidney disease.
PMID- 28409347
TI - Origin and Function of the Renal Stroma in Health and Disease.
AB - The renal stroma is defined as a heterogeneous population of cells that serve
both as a supportive framework and as a source of specialized cells in the renal
capsule, glomerulus, vasculature, and interstitium. In this chapter, we review
published evidence defining what, where, and why stromal cells are important. We
describe the functions of the renal stroma andhow stromal derivatives are crucial
for normal kidney function. Next, we review the specification of stromal cells
from the Osr1+ intermediate mesoderm and T+ presomitic mesoderm during
embryogenesis and stromal cell differentiation. We focus on stromal signaling
mechanisms that act in both a cell and non-cell autonomous manner in
communication with the nephron progenitor and ureteric lineages. To conclude,
stromal cells and the contribution of stromal cells to renal fibrosis and chronic
kidney disease are described.
PMID- 28409348
TI - Imaging, Analysing and Interpreting Branching Morphogenesis in the Developing
Kidney.
AB - The kidney develops as an outgrowth of the epithelial nephric duct known as the
ureteric bud, in a position specified by a range of rostral and caudal factors
which serve to ensure two kidneys form in the appropriate positions in the body.
At its simplest level, kidney development can be viewed as the process by which
this single bud then undergoes a process of arborisation to form a complex
connected network of ducts which will serve to drain urine from the nephrons in
the adult organ. The process of bud elaboration is dictated by factors expressed
by both the bud itself and by surrounding cells of the metanephric mesenchyme
which control cell division and bifurcation. These cells play two critical roles.
Firstly, they potentiate the ongoing elaboration of the ureteric tree: remove
them and branching ceases. Secondly, they harbour progenitor cells which are
fated to undergo their own process of tubulogenesis to form the nephrons of the
adult organ. In this chapter, we will discuss how the ureteric bud arises in the
developing embryo, how it undergoes branching, how we can measure and study this
process and finally the likely relevance that this process has for our
understanding of congenital and acquired kidney disease.
PMID- 28409349
TI - Genetic Syndromes Affecting Kidney Development.
AB - Renal anomalies are common birth defects that may manifest as a wide spectrum of
anomalies from hydronephrosis (dilation of the renal pelvis and calyces) to renal
aplasia (complete absence of the kidney(s)). Aneuploidies and mosaicisms are the
most common syndromes associated with CAKUT. Syndromes with single gene and renal
developmental defects are less common but have facilitated insight into the
mechanism of renal and other organ development. Analysis of underlying genetic
mutations with transgenic and mutant mice has also led to advances in our
understanding of mechanisms of renal development.
PMID- 28409350
TI - Primary Cilia in Cystic Kidney Disease.
AB - Primary cilia are small, antenna-like structures that detect mechanical and
chemical cues and transduce extracellular signals. While mammalian primary cilia
were first reported in the late 1800s, scientific interest in these sensory
organelles has burgeoned since the beginning of the twenty-first century with
recognition that primary cilia are essential to human health. Among the most
common clinical manifestations of ciliary dysfunction are renal cysts. The
molecular mechanisms underlying renal cystogenesis are complex, involving
multiple aberrant cellular processes and signaling pathways, while initiating
molecular events remain undefined. Autosomal Dominant Polycystic Kidney Disease
is the most common renal cystic disease, caused by disruption of polycystin-1 and
polycystin-2 transmembrane proteins, which evidence suggests must localize to
primary cilia for proper function. To understand how the absence of these
proteins in primary cilia may be remediated, we review intracellular trafficking
of polycystins to the primary cilium. We also examine the controversial
mechanisms by which primary cilia transduce flow-mediated mechanical stress into
intracellular calcium. Further, to better understand ciliary function in the
kidney, we highlight the LKB1/AMPK, Wnt, and Hedgehog developmental signaling
pathways mediated by primary cilia and misregulated in renal cystic disease.
PMID- 28409351
TI - Inflammation and Fibrosis in Polycystic Kidney Disease.
AB - Polycystic kidney disease (PKD) is a commonly inherited disorder characterized by
cyst formation and fibrosis (Wilson, N Engl J Med 350:151-164, 2004) and is
caused by mutations in cilia or cilia-related proteins, such as polycystin 1 or 2
(Oh and Katsanis, Development 139:443-448, 2012; Kotsis et al., Nephrol Dial
Transplant 28:518-526, 2013). A major pathological feature of PKD is the
development of interstitial inflammation and fibrosis with an associated
accumulation of inflammatory cells (Grantham, N Engl J Med 359:1477-1485, 2008;
Zeier et al., Kidney Int 42:1259-1265, 1992; Ibrahim, Sci World J 7:1757-1767,
2007). It is unclear whether inflammation is a driving force for cyst formation
or a consequence of the pathology (Ta et al., Nephrology 18:317-330, 2013) as in
some murine models cysts are present prior to the increase in inflammatory cells
(Phillips et al., Kidney Blood Press Res 30:129-144, 2007; Takahashi et al., J Am
Soc Nephrol JASN 1:980-989, 1991), while in other models the increase in
inflammatory cells is present prior to or coincident with cyst initiation (Cowley
et al., Kidney Int 43:522-534, 1993, Kidney Int 60:2087-2096, 2001). Additional
support for inflammation as an important contributor to cystic kidney disease is
the increased expression of many pro-inflammatory cytokines in murine models and
human patients with cystic kidney disease (Karihaloo et al., J Am Soc Nephrol
JASN 22:1809-1814, 2011; Swenson-Fields et al., Kidney Int, 2013; Li et al., Nat
Med 14:863-868, 2008a). Based on these data, an emerging model in the field is
that disruption of primary cilia on tubule epithelial cells leads to abnormal
cytokine cross talk between the epithelium and the inflammatory cells
contributing to cyst growth and fibrosis (Ta et al., Nephrology 18:317-330,
2013). These cytokines are produced by interstitial fibroblasts, inflammatory
cells, and tubule epithelial cells and activate multiple pathways including the
JAK-STAT and NF-kappaB signaling (Qin et al., J Am Soc Nephrol JASN 23:1309-1318,
2012; Park et al., Am J Nephrol 32:169-178, 2010; Bhunia et al., Cell 109:157
168, 2002). Indeed, inflammatory cells are responsible for producing several of
the pro-fibrotic growth factors observed in PKD patients with fibrosis (Nakamura
et al., Am J Nephrol 20:32-36, 2000; Wilson et al., J Cell Physiol 150:360-369,
1992; Song et al., Hum Mol Genet 18:2328-2343, 2009; Schieren et al., Nephrol
Dial Transplant 21:1816-1824, 2006). These growth factors trigger epithelial cell
proliferation and myofibroblast activation that stimulate the production of
extracellular matrix (ECM) genes including collagen types 1 and 3 and
fibronectin, leading to reduced glomerular function with approximately 50% of
ADPKD patients progressing to end-stage renal disease (ESRD). Therefore,
treatments designed to reduce inflammation and slow the rate of fibrosis are
becoming important targets that hold promise to improve patient life span and
quality of life. In fact, recent studies in several PKD mouse models indicate
that depletion of macrophages reduces cyst severity. In this chapter, we review
the potential mechanisms of interstitial inflammation in PKD with a focus on
ADPKD and discuss the role of interstitial inflammation in progression to
fibrosis and ESRD.
PMID- 28409352
TI - Epithelial to Mesenchymal Transition (EMT) and Endothelial to Mesenchymal
Transition (EndMT): Role and Implications in Kidney Fibrosis.
AB - Tubulointerstitial injury is one of the hallmarks of renal disease. In
particular, interstitial fibrosis has a prominent role in the development and
progression of kidney injury. Collagen-producing fibroblasts are responsible for
the ECM deposition. However, the origin of those activated fibroblasts is not
clear. This chapter will discuss in detail the concept of epithelial to
mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) in
the context of fibrosis and kidney disease. In short, EMT and EndMT involve a
change in cell shape, loss of polarity and increased motility associated with
increased collagen production. Thus, providing a new source of fibroblasts.
However, many controversies exist regarding the existence of EMT and EndMT in
kidney disease, as well as its burden and role in disease development. The aim of
this chapter is to provide an overview of the concepts and profibrotic pathways
and to present the evidence that has been published in favor and against EMT and
EndMT.
PMID- 28409353
TI - Assessment of spatial distribution of soil heavy metals using ANN-GA, MSLR and
satellite imagery.
AB - This study aims to assess and compare heavy metal distribution models developed
using stepwise multiple linear regression (MSLR) and neural network-genetic
algorithm model (ANN-GA) based on satellite imagery. The source identification of
heavy metals was also explored using local Moran index. Soil samples (n = 300)
were collected based on a grid and pH, organic matter, clay, iron oxide contents
cadmium (Cd), lead (Pb) and zinc (Zn) concentrations were determined for each
sample. Visible/near-infrared reflectance (VNIR) within the electromagnetic
ranges of satellite imagery was applied to estimate heavy metal concentrations in
the soil using MSLR and ANN-GA models. The models were evaluated and ANN-GA model
demonstrated higher accuracy, and the autocorrelation results showed higher
significant clusters of heavy metals around the industrial zone. The higher
concentration of Cd, Pb and Zn was noted under industrial lands and irrigation
farming in comparison to barren and dryland farming. Accumulation of industrial
wastes in roads and streams was identified as main sources of pollution, and the
concentration of soil heavy metals was reduced by increasing the distance from
these sources. In comparison to MLSR, ANN-GA provided a more accurate indirect
assessment of heavy metal concentrations in highly polluted soils. The clustering
analysis provided reliable information about the spatial distribution of soil
heavy metals and their sources.
PMID- 28409354
TI - Retrosplenial cortical thinning as a possible major contributor for cognitive
impairment in HIV patients.
AB - OBJECTIVES: To identify brain cortical regions relevant to HIV-associated
neurocognitive disorder (HAND) in HIV patients. METHODS: HIV patients with HAND
(n = 10), those with intact cognition (HIV-IC; n = 12), and age-matched,
seronegative controls (n = 11) were recruited. All participants were male and
underwent 3-dimensional T1-weighted imaging. Both vertex-wise and region of
interest (ROI) analyses were performed to analyse cortical thickness. RESULTS:
Compared to controls, both HIV-IC and HAND showed decreased cortical thickness
mainly in the bilateral primary sensorimotor areas, extending to the prefrontal
and parietal cortices. When directly comparing HIV-IC and HAND, HAND showed
cortical thinning in the left retrosplenial cortex, left dorsolateral prefrontal
cortex, left inferior parietal lobule, bilateral superior medial prefrontal
cortices, right temporoparietal junction and left hippocampus, and cortical
thickening in the left middle occipital cortex. Left retrosplenial cortical
thinning showed significant correlation with slower information processing,
declined verbal memory and executive function, and impaired fine motor skills.
CONCLUSIONS: This study supports previous research suggesting the selective
vulnerability of the primary sensorimotor cortices and associations between
cortical thinning in the prefrontal and parietal cortices and cognitive
impairment in HIV-infected patients. Furthermore, for the first time, we propose
retrosplenial cortical thinning as a possible major contributor to HIV-associated
cognitive impairment. KEY POINTS: * Primary sensorimotor and supplementary motor
cortices were selectively vulnerable to HIV infection * Prefrontal and parietal
cortical thinning was associated with HIV-associated cognitive impairment *
Retrosplenial cortical thinning might be a major contributor to HIV-associated
cognitive impairment.
PMID- 28409355
TI - Percutaneous MR-guided focal cryoablation for recurrent prostate cancer following
radiation therapy: retrospective analysis of iceball margins and outcomes.
AB - OBJECTIVES: To evaluate iceball margins after magnetic resonance (MR)-guided
focal salvage prostate cryoablation and determine the correlation with local
outcome. METHODS: A retrospective review was performed on 47 patients that
underwent percutaneous MR-guided focal cryoablation for biopsy-proven locally
recurrent prostate cancer after primary radiotherapy. Preprocedural diagnostic
and intraprocedural MR images were analysed to derive three-directional iceball
margins. Local tumour progression after cryoablation was defined as evident
tumour recurrence on follow-up MRI, positive MR-guided biopsy or biochemical
failure without radiological evidence of metastatic disease. RESULTS: Mean
iceball margins were 8.9 mm (range -7.1 to 16.2), 10.1 mm (range 1.1-20.3) and
12.5 mm (range -1.5 to 22.2) in anteroposterior, left-right and craniocaudal
direction respectively. Iceball margins were significantly smaller for tumours
that were larger (P = .008) or located in the posterior gland (P = .047).
Significantly improved local progression-free survival at 1 year post focal
cryoablation was seen between patients with iceball margin >10 mm (100%), 5-10 mm
(84%) and <5 mm (15%) (P < .001). CONCLUSIONS: Iceball margins appear to
correlate with local outcome following MR-guided focal salvage prostate
cryoablation. Our initial data suggest that freezing should be applied at minimum
5 mm beyond the border of an MR-visible recurrent prostate tumour for successful
ablation, with a wider margin appearing desirable. KEY POINTS: * Shortest iceball
margin most often occurred in anteroposterior direction * Margins were smaller in
tumours that were larger or posteriorly located * Minimum iceball margin was a
predictor of early local tumour progression * A minimum 5-mm margin seems
required for effective cryoablation of recurrent PCa.
PMID- 28409356
TI - FLAIR* to visualize veins in white matter lesions: A new tool for the diagnosis
of multiple sclerosis?
AB - OBJECTIVE: To explore the potential of a post-processing technique combining
FLAIR and T2* (FLAIR*) to distinguish between lesions caused by multiple
sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting.
METHODS: FLAIR and T2* head datasets acquired at 3T of 25 people with relapsing
MS (pwRMS) and ten with pwSVD were used. After post-processing, FLAIR* maps were
used to determine the proportion of white matter lesions (WML) showing the 'vein
in lesion' sign (VIL), a characteristic histopathological feature of MS plaques.
Sensitivity and specificity of MS diagnosis were examined on the basis of >45%
VIL+ and >60% VIL+ WML, and compared with current dissemination in space (DIS)
MRI criteria. RESULTS: All pwRMS had >45% VIL+ WML (range 58-100%) whilst in
pwSVD the proportion of VIL+ WML was significantly lower (0-64%; mean 32+/-20%).
Sensitivity based on >45% VIL+ was 100% and specificity 80% whilst with >60% VIL+
as the criterion, sensitivity was 96% and specificity 90%. DIS criteria had 96%
sensitivity and 40% specificity. CONCLUSION: FLAIR* enables VIL+ WML detection in
a clinical setting, facilitating differentiation of MS from SVD based on brain
MRI. KEY POINTS: * FLAIR* in a clinical setting allows visualization of veins in
white matter lesions. * Significant proportions of MS lesions demonstrate a vein
in lesion on MRI. * Microangiopathic lesions demonstrate a lower proportion of
intralesional veins than MS lesions. * Intralesional vein-based criteria may
complement current MRI criteria for MS diagnosis.
PMID- 28409357
TI - Diffusion-weighted MRI to assess response to chemoradiotherapy in rectal cancer:
main interpretation pitfalls and their use for teaching.
AB - OBJECTIVES: To establish the most common image interpretation pitfalls for non
expert readers using diffusion-weighted imaging (DWI) to assess response to
chemoradiotherapy in patients with rectal cancer and to explore the use of these
pitfalls in an expert teaching setting. METHODS: Two independent non-expert
readers (R1 and R2) scored the restaging DW MRI scans (b1,000 DWI, in conjunction
with ADC maps and T2-W MRI scans for anatomical reference) in 100 patients for
the likelihood of a complete response versus residual tumour using a five-point
confidence score. The readers received expert feedback and the final response
outcome for each case. The supervising expert documented any potential
interpretation errors/pitfalls discussed for each case to identify the most
common pitfalls. RESULTS: The most common pitfalls were the interpretation of low
signal on the ADC map, small susceptibility artefacts, T2 shine-through effects,
suboptimal sequence angulation and collapsed rectal wall. Diagnostic performance
(area under the ROC curve) was 0.78 (R1) and 0.77 (R2) in the first 50 patients
and 0.85 (R1) and 0.85 (R2) in the final 50 patients. CONCLUSIONS: Five main
image interpretation pitfalls were identified and used for teaching and feedback.
Both readers achieved a good diagnostic performance with an AUC of 0.85. KEY
POINTS: * Fibrosis appears hypointense on an ADC map and should not be mistaken
for tumour. * Susceptibility artefacts on rectal DWI are an important potential
pitfall. * T2 shine-through on rectal DWI is an important potential pitfall. *
These pitfalls are useful to teach non-experts how to interpret rectal DWI.
PMID- 28409358
TI - Added value of gadoxetic acid-enhanced T1-weighted magnetic resonance
cholangiography for the diagnosis of post-transplant biliary complications.
AB - OBJECTIVES: Biliary complications after liver transplantation (LT) are common.
This study aimed to ascertain the value of gadoxetic acid-enhanced T1-weighted
(T1w) magnetic resonance cholangiography (MRC) to evaluate anastomotic strictures
(AS), non-anastomotic strictures (NAS) and biliary casts (BC). METHODS: Sixty
liver-transplanted patients with suspicion of biliary complications and T2w-MRCP
and T1w-MRC followed by endoscopic retrograde cholangiopancreatography (ERCP) or
percutaneous transhepatic cholangiography (PTC) were analysed. Two readers
reviewed the MRCs and rated image quality (IQ) and likelihood for AS/NAS/BC on
Likert scales. Sensitivity, specificity and predictive values were calculated,
ROC curve analysis performed, and inter-reader variability assessed. The
subjective added value of T1w-MRC was rated. RESULTS: IQ was high for all
sequences without significant differences (2.83-2.88). In 39 patients ERCP/PTC
detected a complication. Sensitivity and specificity for AS were 64-96 using T2w
MRCP, increasing to 79-100 using all sequences. Use of all sequences increased
the sensitivity of detecting NAS/BC from 72-92% to 88-100% and 67-89% to 72-94%,
respectively. Kappa values were substantial (0.45-0.62). T1w-MRC was found to be
helpful in 75-83.3%. CONCLUSIONS: Combining T1w-MRC and T2w-MRCP increased
sensitivity and specificity and diagnostic confidence in patients after LT with
suspected biliary complications. T1w-MRC is a valuable tool for evaluating post
transplant biliary complications. KEY POINTS: * T1w-MRC is a valuable tool for
evaluating post-transplant biliary complications. * Adding T1w-MRC to T2w-MRC
increases diagnostic confidence for detection of biliary complications. * A
combination of T1w-MRC and T2w-MRCP leads to the best results.
PMID- 28409360
TI - Voices from Flint: Community Perceptions of the Flint Water Crisis.
AB - We describe the self-reported socioeconomic and health impacts, as well as the
coping mechanisms employed by a drug-using cohort of adults during the Flint
water crisis (FWC) in Flint, Michigan. Participants from an ongoing longitudinal
Emergency Department study were contacted between April 2016 and July 2016 and
completed a survey focusing on exposure, consequences, and coping strategies. One
hundred thirty-three participants (mean age = 26, 65% African-American, 61%
public assistance) completed the survey (37.9% response rate). Of these, 75%
reported exposure to water with elevated lead levels. Of these, 75% reported
additional monthly expenses resulting from exposure. Almost 40% of parents
reported changes in their children's health and 65% reported changes to their
health since the FWC. Participants indicated the use of both positive (e.g.,
advice from trusted neighbors, 99.0%) and negative coping mechanisms (e.g.,
increased substance use, 20.0%) in response to this public health emergency. High
risk Flint residents reported multiple social, economic, and health-related
consequences stemming from the FWC. Policymakers should consider additional
resources for those affected, including increased access to mental health to aid
recovery within the community.
PMID- 28409359
TI - On the Battlefield: The Black Church, Public Health, and the Fight against HIV
among African American Gay and Bisexual Men.
AB - HIV affects African American gay and bisexual men (AAGBM) more disproportionately
than any other group in the USA. The Black Church, which has been a historic
mainstay for African American empowerment and well-being, has the potential to be
a public health partner for HIV prevention with AAGBM. Public health partnerships
with the Black Church can strengthen HIV prevention efforts with AAGBM by [1]
adapting church-based prevention strategies developed for other African American
subgroups [2], providing prevention and referral services [3], considering how
scripture supports prevention efforts, and [4] emphasizing the tenets of
liberation theology. Public health should consider how thoughtful engagement,
research, and interventions can support these approaches. Developing partnerships
with the Black Church and African American clergy can promote effective HIV
prevention efforts for AAGBM.
PMID- 28409361
TI - Psychometric Properties of the Spence Children's Anxiety Scale: Parent Report in
Children with Autism Spectrum Disorder.
AB - Although anxiety is frequently reported in children with autism spectrum disorder
(ASD), existing anxiety scales are often psychometrically inappropriate for this
population. This study examined the internal structure, reliability, convergent
and discriminant validity of the Spence Children's Anxiety Scale-Parent Report
(SCAS-P; Spence 1999) in 238 school-aged children with ASD. While confirmatory
factor analysis did not support the original six-correlated-factor structure,
structural support as well as acceptable internal consistency and convergent
validity was found for Generalized Anxiety, Separation Anxiety, Panic, and
Agoraphobia subscales. Use of the SCAS-P in its original form for assessment in
children with ASD was not supported. However, four subscales showed viability,
and may benefit re-analyses of existing SCAS-P data and future scale adaptations
for research and clinical purposes.
PMID- 28409362
TI - The antibacterial agent, moxifloxacin inhibits virulence factors of Candida
albicans through multitargeting.
AB - Fluoroquinolines are broad spectrum fourth generation antibiotics. Some of the
Fluoroquinolines exhibit antifungal activity. We are reporting the potential
mechanism of action of a fluoroquinoline antibiotic, moxifloxacin on the growth,
morphogenesis and biofilm formation of the human pathogen Candida albicans.
Moxifloxacin was found to be Candidacidal in nature. Moxifloxacin seems to
inhibit the yeast to Hyphal morphogenesis by affecting signaling pathways. It
arrested the cell cycle of C. albicans at S phase. Docking of moxifloxacin with
predicted structure of C. albicans DNA Topoisomerase II suggests that
moxifloxacin may bind and inhibit the activity of DNA Topoisomerase II in C.
albicans. Moxifloxacin could be used as a dual purpose antibiotic for treating
mixed infections caused by bacteria as well as C. albicans. In addition chances
of developing moxifloxacin resistance in C. albicans are less considering the
fact that moxifloxacin may target multiple steps in yeast to hyphal transition in
C. albicans.
PMID- 28409363
TI - Advances in the treatment of problematic industrial biofilms.
AB - In nature, microorganisms tend to form biofilms that consist of extracellular
polymeric substances with embedded sessile cells. Biofilms, especially mixed
culture synergistic biofilm consortia, are notoriously difficult to treat. They
employ various defense mechanisms against attacks from antimicrobial agents.
Problematic industrial biofilms cause biofouling as well as biocorrosion, also
known as microbiologically influenced corrosion. Biocides are often used to treat
biofilms together with scrubbing or pigging. Unfortunately, chemical treatments
suppress vulnerable microbial species while allowing resistant species to take
over. Repeated treatment cycles are typically needed in biofilm mitigation. This
leads to biocide dosage escalation, causing environmental problems, higher costs
and sometimes operational problems such as scale formation. New treatment methods
are being developed such as enhanced biocide treatment and bacteriophage
treatment. Special materials such as antibacterial stainless steels are also
being created to combat biofilms. This review discussed some of the advances made
in the fight against problematic industrial biofilms.
PMID- 28409364
TI - Distraction and proficiency in laparoscopy: 2D versus robotic console 3D
immersion.
AB - INTRODUCTION: Studies have shown that using robotic-assisted laparoscopy (RL)
increases performance compared to conventional laparoscopy (CL) due to its
mechanical advantages but have not assessed distraction as a factor. To determine
whether the immersive aspect of the 3D optics in RL contributes to improved
performance, we compared the outcomes of laparoscopic skills by using just the 3D
optics of the da Vinci versus the conventional 2D monitor with and without
distraction. METHODS: Thirty-two participants without any laparoscopic experience
were randomized evenly into four groups: RL, robotic-assisted laparoscopy with
distraction (RL + D), CL, and conventional laparoscopy with distraction (CL + D).
Each participant performed three Fundamentals of Laparoscopy Surgery tasks [peg
transfer (Task 1), circle cutting (Task 2), and suturing with knot (Task 3)] for
three repetitions. For each task, the mean time and errors were recorded and
analyzed statistically for each group. RESULTS: Compared to other groups, CL + D
took on average 1 min longer to complete Task 1 (P = 0.001), more than 1 min to
complete Task 2 (P = 0.003), and more than 2 min to complete the Task 3 (P <
0.001). On Task 2, the deviations from the pattern were shorter for RL and RL + D
compared to CL and CL + D (mean 0.33 and 0.37 cm vs. 0.55 and 0.58 cm,
respectively; P < 0.001). On Task 3, the deviations were also shorter for RL and
RL + D compared to CL and CL + D (mean 0.23 and 0.24 mm vs. 0.61 and 0.63 mm,
respectively; P < 0.001). CONCLUSION: When distraction was introduced, CL
performed significantly worse. This suggests that using the conventional 2D
monitor does not help with blocking out distraction. For Tasks 2 and 3, which
require more precision and depth perception, the groups that used the 3D optics
had shorter mean deviations than groups that used the conventional 2D monitor.
This suggests that even when the robotic arms of the da Vinci are removed, there
are still advantages to the immersive 3D optics, especially when distraction is
present. The immersive aspect of the 3D optics may help improve performance in
the OR, allowing surgeons to be more focused on the case and have greater depth
acuity.
PMID- 28409365
TI - Troubleshooting common endoscopic malfunctions: a study integrating a
preoperative checklist and troubleshooting guide into surgical resident training.
AB - INTRODUCTION: This study assessed the utility of a checklist in troubleshooting
endoscopic equipment. Prior studies have demonstrated that performance in
simulated tasks translates into completion of similar tasks in the operating
room. Checklists have been shown to decrease error and improve patient safety.
There is currently limited experience with the use of simulation and checklists
to improve troubleshooting of endoscopic equipment. We propose the use of a
checklist during a simulated colonoscopy to improve performance during endoscopic
troubleshooting. METHODS: This study randomized 20 surgical residents (PGY1-3)
who were blinded to the purpose of the simulation. Participants were asked to
complete two consecutive colonoscopies in a mock endoscopy suite. Prior to each
trial, a standard set of equipment malfunctions were created; the equipment was
returned to working order if the subjects were unable to successfully
troubleshoot the equipment within the first 3 min of the simulation. Between
trials, the intervention group was provided a troubleshooting checklist, which
they were permitted to utilize during the second trial. The control group had no
intervention. Scores were calculated for each task by subtracting time to
completion from total time allowed (180 s), with 0 indicating the task was not
completed. Groups were compared utilizing unpaired Student's t-test with p < 0.05
threshold for significance. RESULTS: Average scores were compared for 5 tasks in
the first trial and 6 tasks in the second trial. During the first trial, there
were no significant differences. However, during the second trial, there was a
significant improvement with the checklist for 5/6 tasks. CONCLUSION: Use of a
checklist, with no further intervention, significantly improves the ability of
novice endoscopists to identify and remedy common equipment malfunctions.
Introduction of a troubleshooting checklist may represent a simple and low-cost
way to improve both efficiency and safety in the endoscopy suite.
PMID- 28409366
TI - Local and national laparoscopic skill competitions: residents' opinions and
impact on adoption of simulation-based training.
AB - BACKGROUND: Dedicated practice using laparoscopic simulators improves operative
performance. Yet, voluntary utilization is minimal. We hypothesized that skill
competition between peers, at the local and national level, positively influences
residents' use of laparoscopic simulators. METHODS: A web-based survey evaluated
the relationship between Canadian General Surgery residents' use of laparoscopic
simulation and participation in competition. Secondary outcomes assessed
attitudes regarding simulation training, factors limiting use, and associations
between competition level and usage. RESULTS: One hundred ninety (23%) of 826
potential participants responded. Eighty-three percent rated their laparoscopic
abilities as novice or intermediate. More than 70% agreed that use of simulation
practice improves intra-operative performance, and should be a mandatory
component of training. However, 58% employed simulator practice less than once
per month, and 18% never used a simulator. Sixty-five percent engaged in
simulator training for 5 h or less over the preceding 6 months. Seventy-three
percent had participated in laparoscopic skill competition. Of those, 51% agreed
that competition was a motivation for simulation practice. No association was
found between those with competition experience and simulator use. However, 83%
of those who had competed nationally reported >5 h of simulator use in the
previous 6 months compared to those with no competition experience (26%), local
competition (40%), and local national-qualifying competition (23%) (p < 0.001).
CONCLUSIONS: This study does not support the hypothesis that competition alone
universally increases voluntary use of simulation-based training, with only the
minority of individuals competing at the national level demonstrated
significantly higher simulation use. However, simulation training was perceived
as a valuable exercise. Lack of time and access to simulators, as opposed to lack
of interest, were the most commonly reported to limited use.
PMID- 28409367
TI - The effect of health system factors on outcomes and costs after bariatric surgery
in a universal healthcare system: a national cohort study of bariatric surgery in
Canada.
AB - INTRODUCTION: Previous data demonstrate that patients who receive bariatric
surgery at a Center of Excellence are different than those who receive care at
non-accredited centers. Canada provides a unique opportunity to naturally exclude
confounders such as insurance status, hospital ownership, and lack of access on
comparisons between hospitals and surgeons in bariatric surgery outcomes. The
objective of this study was to determine the effect of hospital accreditation and
other health system factors on all-cause morbidity after bariatric surgery in
Canada. METHODS: This was a population-based study of all patients aged >=18 who
received a bariatric procedure in Canada (excluding Quebec) from April 2008 until
March 2015. The main outcomes for this study were all-cause morbidity and costs
during the index admission. All-cause morbidity included any documented
complication which extended length of stay by 24 h or required reoperation. Risk
adjusted hierarchical regression models were used to determine predictors of
morbidity and cost. RESULTS: Overall, 18,398 patients were identified and the all
cause morbidity rate was 10.1%. Surgeon volume and teaching hospitals were both
found to significantly decrease the odds of all-cause morbidity. Specifically,
for each increase in 25 bariatric cases per year, the odds of all-cause morbidity
was 0.94 times lower (95% CI 0.87-1.00, p = 0.03). Teaching hospitals conferred a
0.75 lower odds of all-cause morbidity (95% CI 0.58-0.95, p < 0.001).
Importantly, formal accreditation was not associated with a decrease in all-cause
morbidity within a universal healthcare system. No health system factors were
associated with significant cost differences. CONCLUSION: This national cohort
study found that surgeon volume and teaching hospitals predicted lower all-cause
morbidity after surgery while hospital accreditation was not a significant
factor.
PMID- 28409368
TI - Comparison of OrVilTM and RPD in laparoscopic total gastrectomy for gastric
cancer.
AB - BACKGROUND: Laparoscopic total gastrectomy (LTG) is frequently performed for
treating patients with gastric cancer; however, the absence of anastomotic
techniques with greater superiority has impaired its popularization. We have
compared two types of anastomotic techniques with regard to technical
perspectives and clinical outcomes. METHODS: We reviewed 43 patients with gastric
cancer who underwent LTG. Two types of anastomotic techniques have been applied
after LTG-the trans-orally inserted anvil (OrVilTM) and the reverse puncture
device (RPD). Data on the type of anastomosis, blood loss, operation time,
anastomosis time, location of tumors, distance between the top border of tumors
and top resection margin, diameter of tumor, length of postoperative hospital
stay, early and late postoperative complications, and total cost of surgical
consumables were obtained by reviewing patient medical records and analyzed
thereafter. RESULTS: We included 32 men and 11 women (mean age 61 years). The
loss to follow-up rate was 13.2%. The median survival time for the OrVilTM and
RPD groups was 23 and 22 months, respectively. The total rate of complications
was 9.3%. The difference in the anastomosis times between the groups was
statistically significant. OrVilTM required more time than RPD and cost more than
RPD. CONCLUSIONS: Both the OrVilTM and RPD techniques showed good safety and
applicability in LTG. RPD showed an advantage with regard to lesser operative
complexity and lower cost.
PMID- 28409369
TI - Laparoscopic surgery for choledocholithiasis concomitant with calculus of the
left intrahepatic duct or abdominal adhesions.
AB - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has been widely
promoted in recent years as a safe and effective treatment for
choledocholithiasis. However, there are no standard guidelines for the treatment
of patients who have concomitant hepatolithiasis of the left liver and abdominal
adhesions. The aim of the current research was to compare the outcomes of open
versus laparoscopic common bile duct exploration with left hepatectomy (OCBDH vs.
LCBDH) in patients with choledocholithiasis concomitant with left-sided
hepatolithiasis, and to evaluate the safety and feasibility of laparoscopic
surgery for choledocholithiasis in patients with abdominal adhesions. METHODS:
Between October 2012 and October 2015, a total of 321 consecutive patients with
choledocholithiasis underwent surgical treatment. LCBDE was performed in 107
patients, and open common bile duct exploration (OCBDE) was performed in 111
patients. Further, 31 patients and 72 patients underwent LCBDH and OCBDH,
respectively. A total of 133 patients who underwent LCBDE or OCBDE had abdominal
adhesions, which were classified as mild, moderate, or severe according to an
abdominal adhesion scoring system, which was validated in the LCBDE group and
OCBDE group. The perioperative results were reviewed and analyzed
retrospectively. RESULTS: In the mild adhesion group, blood loss, postoperative
recovery in the LCBDE group was lesser than those in the OCBDE group. In the
moderate adhesion group, the postoperative recovery was significantly shorter in
the LCBDE group than in the OCBDE group. In the severe adhesion group, the
operation time and blood loss in the LCBDE group were higher than those in the
OCBDE group. The postoperative recovery was significantly better in the LCBDH
group than in the OCBDH group. CONCLUSION: LCBDH can obviously improve recovery
and shorten the hospitalization period. Further, LCBDE is safe and feasible for
patients of choledocholithiasis with mild and moderate abdominal adhesions.
PMID- 28409370
TI - A plea for thoracoscopic resection of solitary pulmonary nodule in cancer
patients.
AB - BACKGROUND: Solitary pulmonary nodules (SPN) are frequently detected in cancer
patients. These lesions are often considered as pulmonary metastases and
increasingly treated by non-surgical techniques without histological
confirmation. The aim of this study is to determine the histological nature of
SPN resected by thoracoscopy and to identify risk factors of malignancy. METHODS:
Single-institution retrospective analysis of all consecutive patients with
previously known malignancies who underwent thoracoscopic resection of SPN with
unknown diagnosis between 2001 and 2014. RESULTS: One hundred and forty cancer
patients underwent thoracoscopic resection of a SPN. The resected SPN was benign
in 34 patients (24.3%) and malignant in 106 patients. The latter were metastasis
in 70 patients (50%) and a primary lung cancer in 36 patients (25.7%). Upon
univariate analysis, malignancy was significantly associated with age >60 years,
disease-free interval >=24 months, SPN size >8 mm, upper lobe localization and
SUVmax > 2.5 on PET-CT. Upon multivariate analysis, upper lobe localization and
SUVmax > 2.5 were associated with malignancy. Smoking was significantly
associated with SPN containing primary lung cancer. CONCLUSION: In this series,
only 50% of SPN in patients with known malignant disease were pulmonary
metastases and 25% had a newly diagnosed NSCLC. Smoking was associated with
primary lung cancer but no other predictor was found to allow the distinction
between pulmonary metastasis and lung cancer. These results endorse the need of
histological confirmation of SPN in patients with previous malignancies to avoid
diagnostic uncertainty and suboptimal treatments.
PMID- 28409371
TI - Dynamic analysis of commonly used biochemical parameters to predict common bile
duct stones in patients undergoing laparoscopic cholecystectomy.
AB - BACKGROUND: The prediction of persistent common bile duct stones (CBDS) in
patients during choledocholithiasis crisis is challenging. We developed a model
based on the course over time of commonly used biochemical parameters to reduce
the rate of unnecessary endoscopic cholangiopancreatography (ERCP) and the risk
of perioperative discovery of CBDS. METHODS: Medical charts of patients who
presented between 2010 and 2015 for symptomatic gallstone disease with suspected
choledocholithiasis were reviewed and compared according to the presence/absence
of CBDS on preoperative ERCP or during cholecystectomy. RESULTS: 210 patients
were included. Unnecessary ERCP and the discovery rate of CBDS were 9.0 and
22.4%, respectively. Multivariate analysis demonstrated age >=80 years,
neutrophils >=12000/uL and gamma-glutamyl transpeptidase (GGT) >=300 units/L at
admission, alkaline phosphatase >=180 units/L at days 3-5 post admission, and a
decrease in C-reactive protein <=10%, aspartate aminotransferase <=35%, GGT
<=25%, and total bilirubin <=15% between day 0 and days 3-5 to be predictive of
CBDS. The area under the receiver-operator characteristic curve was 0.881. When
used to select patients for preoperative ERCP, diagnostic accuracy was 94.8% when
three predictors were present. Negative and positive predictive values were 100%
in the absence of predictors and when five predictors were present, respectively.
Unnecessary ERCP and CBDS discovery rates both decreased to 2.6%. CONCLUSIONS:
Commonly used biochemical parameters correctly predict CBDS when they are
analysed in a dynamic setting rather than at discrete time points. The proposed
model constitutes a reliable tool to decrease unnecessary ERCP and perioperative
discovery rates of CBDS.
PMID- 28409372
TI - Primary hyperparathyroidism treated by transoral endoscopic parathyroidectomy
vestibular approach (TOEPVA).
AB - BACKGROUND: Bilateral open cervical exploration with identifying all parathyroid
glands and removing one or more enlarged parathyroid tumor(s) was the standard of
care in primary hyperparathyroidism (pHPT). With the introduction of preoperative
imaging and intraoperative parathyroid hormone (IOPTH) measurements [1, 2],
various minimally invasive parathyroidectomy approaches have been developed, both
open and endoscopic [3-8]. The most commonly used approach currently in the USA
is the minimally invasive open parathyroidectomy (MIP), which can be performed in
the ambulatory setting with excellent cure and minimal complication rates [9-12].
However, the operation requires a cervical incision, with occasionally poor
cosmesis. The transoral endoscopic parathyroidectomy vestibular approach (TOEPVA)
provides a novel "scarless" approach to parathyroid surgery. METHODS: The aim of
the video is to provide detailed instruction of the TOEPVA in pHPT and how to
interpret IOPTH measurements in this setting. RESULTS: The TOEPVA uses three
incisions in the vestibule of the oral cavity, using two 5-mm ports and one
central 11-mm port. The subplatysmal space is enlarged by hydrodissection and
manual dilation. The working space is enhanced by insufflation to 6 mmHg. With
the adjunct of preoperative imaging and IOPTH measurements, the extent of the
operation is tailored to achieve biochemical cure. CONCLUSIONS: TOEPVA is
feasible and safe and provides an excellent cosmetic outcome. It is a more direct
approach than other remote endoscopic parathyroidectomy techniques. TOEPVA is an
excellent option for select patients with pHPT wishing to avoid a neck incision.
PMID- 28409373
TI - A novel method of self-pulling and latter transected delta-shaped Billroth-I
anastomosis in totally laparoscopic distal gastrectomy.
AB - BACKGROUND: We developed a modified delta-shaped gastroduodenostomy technique in
totally laparoscopic distal gastrectomy. This novel technique, which effectively
reduces the required quantity of linear stapler [1-3], was named as self-pulling
and latter transected delta-shaped anastomosis (Delta SPLT) [4]. METHODS: Delta
SPLT was performed on 15 patients with stage cT1-2 antral cancer. We ligated the
duodenum with a rope instead of transecting it and used the ligature rope to pull
the duodenum during the whole progress of gastroduodenostomy. When closing the
entry hole, the duodenum was transected at the same time, which saved one linear
stapler. Data of clinicopathologic characteristics, surgical and postoperative
outcomes were collected and expressed as means +/- standard deviations. RESULTS:
All the operations were successfully performed by using no more than four 60-mm
linear staplers. The mean BMI of the patients is 23.0 +/- 2.5 kg/m2 (range 17.0
26.0 kg/m2), and duration of the operation was 115.0 +/- 33.4 min (range 75-215
min), including 22.3 +/- 6.7 min (range 15-35 min) of reconstruction. Mean blood
loss was 82.7 +/- 71.3 mL (range 10-300 mL), and mean times to first flatus was
2.3 +/- 1.1 days (range 1-5 days). A mean number of 27.5 +/- 5.4 (range 18-38)
lymph nodes was retrieved. Overall postoperative morbidity rate was 6.7% (1/15).
There was no anastomosis-related complication, but one case of pneumonia
developed on postoperative day (POD) 2 which was successfully managed by
conservative methods. Patients were discharged (POD mean 5.8 +/- 1.3, range 4-9)
when their bowel movements recovered and no discomfort with soft diet was
claimed. CONCLUSION: Delta SPLT is a safe and feasible technique and requires
less clinical costs.
PMID- 28409374
TI - Self-expandable metal stent placement versus emergency resection for malignant
proximal colon obstructions.
AB - BACKGROUND: Traditionally, all patients with a malignant obstruction of the
proximal colon (MOPC) are treated with emergency resection. However, recent data
suggest that Self-expandable metallic stent (SEMS) placement could lower
mortality and morbidity rates. This study therefore aimed to compare SEMS
placement with emergency resection as treatment options for MOPC. METHODS: All
consecutive patients that underwent SEMS placement for MOPC in the period 2004
2015 at our institution were identified. SEMS placement was the standard of care
for colonic obstructions at our institution in that period. All included SEMS
patients were matched (1:4) on age (+/-5 years), gender, ASA-score, tumor
location, surgical approach and pTNM-stage with patients treated by emergency
resection. Controls were selected from a national database that prospectively
registers all patients undergoing surgery for colorectal cancer in the
Netherlands. RESULTS: In total, 41 patients received SEMS placement for MOPC. In
19 patients SEMS served as a definite palliative measure and in 22 as bridge to
surgery. Technical and clinical success rates of SEMS placement were 92.7% and
90.2%, respectively. No significant differences between the SEMS and emergency
resection group were found regarding morbidity and mortality rates, the number of
radical resections and the number of primary anastomoses. Patients treated with
SEMS were, however, less likely to have a temporary stoma constructed (p = 0.04).
No SEMS-related complications occurred in patients in whom SEMS was placed as
bridge to surgery, whereas one stent-related perforation, three stent migrations,
and five stent re-obstructions were observed in the palliative group. Three re
obstructions could be treated with re-stenting, but all other SEMS-related
complications required surgical intervention. In the palliative group, SEMS
complications necessitating surgery occurred in 31.6% of the patients (6/19).
CONCLUSION: SEMS placement for MOPC appears to be a relatively feasible and safe
alternative for emergency resection in both the curative and palliative setting.
PMID- 28409375
TI - Fluoroscopy-guided gastric peroral endoscopic pyloromyotomy (G-POEM): a more
reliable and efficient method for treatment of refractory gastroparesis.
AB - INTRODUCTION: Prior studies show promising results of the gastric peroral
endoscopic pyloromyotomy (G-POEM) procedure for treatment of refractory
gastroparesis. One major technical challenge involved in this procedure is
identifying the pyloric muscular ring (PMR). The aim of this study is to
establish a reliable method for identification of the PMR during G-POEM. METHODS:
Fluoroscopy-guided G-POEM was performed by placing an endoclip at the 9 to 11'o
clock position at the pylorus for identification of PMR. Conventional G-POEM was
performed by observation of blue colored mucosa at the pylorus area as an
indirect marker for PMR. The degree of the PMR identification was graded into
well identified, identified, and not identified based on the appearance of the
PMR. Procedure times were accurately documented. Gastroparesis cardinal symptoms
index and gastric emptying scintigraphy were evaluated before and after the
procedure. RESULTS: Fourteen patients were studied, seven underwent fluoroscopy
guided G-POEM, and seven patients underwent conventional G-POEM. All procedures
achieved technical success and no adverse events occurred. In the seven patients
who underwent fluoroscopy-guided G-POEM, the PMR was well identified in four
patients and identified in three patients. In the seven patients who underwent
conventional G-POEM, the PMR was identified in four patients and not identified
in three patients. The average time to complete the fluoroscopy-guided G-POEM was
significantly shorter than that of the conventional G-POEM. CONCLUSIONS:
Fluoroscopy-guided G-POEM by placement of an endoclip at the pylorus was a
reliable and safe method to direct the orientation of the submucosal tunnel, to
facilitate the location of the PMR, and to shorten the procedure time.
PMID- 28409376
TI - Clinicopathologic features of early gastric carcinoma with lymphoid stroma and
feasibility of endoscopic submucosal dissection.
AB - BACKGROUND: Gastric carcinoma with lymphoid stroma (GCLS) is a rare disease known
to have unique features and a favorable prognosis. This study aimed to determine
the clinicopathologic features of early GCLS (EGCLS) and define the feasibility
of endoscopic submucosal dissection (ESD) for EGCLS. METHODS: We performed a
retrospective analysis of 70 EGCLS patients treated via ESD or surgery and 1626
patients who underwent surgical resection for early non-GCLS (ENGCLS) between
January 2007 and December 2014 at Pusan National University Hospital, Busan,
Republic of Korea. RESULTS: The mean age of EGCLS patients was 58 years (range 36
77 years); a male predominance (3.7:1) was observed, and 81.4% showed Epstein
Barr virus positivity. Compared with ENGCLS, EGCLS was macroscopically more
elevated (34.3 vs. 18.0%, P = 0.003) and located more proximally (upper third:
37.1 vs. 9.7%, P < 0.001). Tumor size was smaller (2.1 +/- 1.1 vs. 3.1 +/- 2.0
cm, P < 0.001), but submucosal invasion was more frequent (77.1 vs. 44.4%, P <
0.001) and deeper in the EGCLS group. Among the 59 EGCLS patients who were
treated surgically, only two (3.4%) showed lymph node metastasis (LNM). Despite
submucosal invasion, EGCLS showed a lower LNM rate (4.0 vs. 19.4%, P = 0.007)
than ENGCLS, even in patients with SM3 EGCLS (5.3 vs. 24.5%, P = 0.007). There
were no recurrences in the available ten patients who underwent ESD alone during
a mean follow-up of 37.2 months. CONCLUSIONS: In this study, we observed unique
clinicopathologic features with a very low LNM rate in EGCLS. We consider ESD a
potentially curative treatment strategy for EGCLS despite deep submucosal
invasion, especially in patients with poor performance status and significant
comorbidities.
PMID- 28409377
TI - Laparoscopic radical antegrade modular pancreatosplenectomy for left-sided
pancreatic cancer using the ligament of Treitz approach.
AB - BACKGROUND: Laparoscopic distal pancreatectomy (Lap-DP) for benign lesions or
those with low malignant potential has been proven safe and effective, and its
performance is now widespread [1-3]. Lap-DP for left-sided pancreatic cancer (PC)
is also being increasingly performed. According to some reports, Lap-DP has
superior short-term outcomes (blood loss, postoperative hospital stay) and
comparable oncological outcomes and overall survival with those of open distal
pancreatectomy (Op-DP) [4-6]. PC has highly malignant potential; thus, complete
resection and sufficient regional lymphadenectomy with tumor-free margins are
very important. Radical antegrade modular pancreatosplenectomy (RAMPS) is an
accepted standard Op-DP technique for PC and is reportedly useful for achieving
R0 resection and radical lymphadenectomy [7-10]. However, laparoscopic RAMPS (Lap
RAMPS) is not yet popular because of its technical difficulty and lack of
adequate evidence. Few reports have described the detailed surgical technique of
Lap-RAMPS [11-13]. We employ Lap-RAMPS using the ligament of Treitz approach with
the benefit of a laparoscopic view and herein describe the usability of this
laparoscopic procedure with a video. METHODS: Our indication for Lap-RAMPS is
left-sided PC located >=1 cm away from the origin of the splenic artery (SPA)
without invasion of the superior mesenteric artery (SMA), celiac artery (CA),
common hepatic artery (CHA), or portal vein (PV). We apply either anterior or
posterior RAMPS to achieve tumor-free margins. Therefore, the left adrenal gland
and the nerve plexus around the SMA and CA are resected depending on the extent
of the cancer. Three patients underwent Lap-RAMPS for left-sided PC using the
ligament of Treitz approach from April to December 2016. This video shows our Lap
RAMPS procedure performed in a 67-year-old man with pancreatic body cancer who
was being followed up for autoimmune pancreatitis. The tumor was suspected to
have invaded the SPA, splenic vein, and retroperitoneum but was not close to the
SMA, CA, CHA, or PV. The patient was put in the supine position with his legs
opened, and the operation was performed using five trocars. Early in the
operation, we incised the retroperitoneum just beside the ligament of Treitz, and
the inferior vena cava and left renal vein (LRV) were exposed with resection of
Gerota's fascia under a good laparoscopic view. The left adrenal gland was
resected in this case to obtain sufficient tumor-free margins. The origin of the
SMA was easily identified above the LRV. The most posterior dissection was
carried out early in the operation, making it easy and safe to determine the
resected margin and enabling curative resection with sufficient regional
lymphadenectomy. After division of the pancreas with a linear stapler, the lymph
nodes around the SMA and CA were safely removed. RESULTS: The operative time was
358 min, and the estimated blood loss was 1 ml. The postoperative course was
uneventful, and the patient was discharged on postoperative day 10. Pathological
examination revealed invasive ductal carcinoma (stage III, T3N1M0 according to
the 7th edition of the Union for International Cancer Control system) with tumor
free margins. In all three patients, the median operative time and blood loss
were 358 (328-451) min and minimal (minimal to 1 ml). One patient underwent
anterior RAMPS and the other two patients, including the case mentioned above,
underwent posterior RAMPS. One patient developed a grade B pancreatic fistula
according to the International Study Group for Pancreatic Fistula (ISGPF)
classification, but he recovered promptly with conservative treatment. No life
threatening complications occurred. The median postoperative hospital stay was 14
(10-16) days. CONCLUSIONS: Lap-RAMPS using the ligament of Treitz approach is
feasible and extremely helpful in performing minimally invasive, curative
resection for well-selected left-sided PC.
PMID- 28409378
TI - Percutaneous cholecystostomy: prognostic factors and comparison to
cholecystectomy.
AB - BACKGROUND: Data regarding long-term outcomes following percutaneous
cholecystostomy (PC) are limited, and comparisons to cholecystectomy (CCY) are
lacking. We hypothesized that chronic disease burden would predict 1-year
mortality following PC, and that outcomes following PC and CCY would be similar
when controlling for preprocedural risk factors. METHODS: We performed a 10-year
retrospective cohort analysis of patients with acute cholecystitis managed by PC
(n = 114) or CCY (n = 234). Treatment response was assessed by systemic
inflammatory response syndrome (SIRS) criteria at PC/CCY and 72 h later. Logistic
regression identified predictors of 30-day and 1-year mortality following PC. PC
and CCY patients were matched by age, Tokyo Guidelines (TG13) cholecystitis
severity grade, and VASQIP calculator predicted mortality (n = 42/group).
RESULTS: The presence of SIRS at 72 h following PC was associated with 30-day
mortality [OR 8.9 (95% CI 2.6-30)]. SIRS at 72 h was present in and 21.4% of all
PC patients, significantly higher than unmatched CCY patients (4.7%, p = 0.048).
Independent predictors of 1-year mortality following PC were DNR status [19.7
(2.1-186)], disseminated cancer [7.5 (2.1-26)], and congestive heart failure [3.9
(1.4-11)]. PC patients with none of these risk factors had 17.9% 90-day mortality
and no deaths after 90 days; late deaths continued to occur among patients with
DNR, CHF, or disseminated cancer. At baseline, PC patients had greater acute and
chronic disease burden than CCY patients. After matching, PC and CCY patients had
similar age (69 vs. 70 years), TG13 grade (2.4 vs. 2.4), and predicted 30-day
mortality (5.5 vs. 6.8%). Matched PC patients had higher 30-day mortality (14.3
vs. 2.4%, p = 0.109) and 180-day mortality (28.6 vs. 7.1%, p = 0.048).
CONCLUSIONS: Treatment response to PC predicted 30-day mortality; DNR status, and
chronic diseases predicted 1-year mortality. Although the matching procedure did
not eliminate selection bias, PC was associated with persistent systemic
inflammation and higher long-term mortality than CCY.
PMID- 28409379
TI - Accuracy and inter-operator variability of small bowel length measurement at
laparoscopy.
AB - BACKGROUND: Measurement of bowel length is an essential surgical skill for
laparoscopic and open gastrointestinal surgery in order to achieve favorable
outcomes and avoid long-term complications. Variations in accuracy between the
two surgical approaches may exist. However, only few studies have tried to assess
these differences. Our aim was to assess reliability and inter-rater variability
of small bowel length assessment during laparoscopy in an in vivo porcine model.
METHODS: This is a single-institution, double-blinded, technical assessment study
in a porcine in vivo model. Fourteen participants (ten senior surgeons with >1000
laparoscopic procedures and four junior surgeons) had to assess and mark lengths
of small bowel in both laparoscopic and open surgical approaches. Each
participant was assigned to measure and mark specific, randomized distances
(range 25-197 cm) in both laparoscopic and open approaches using color-coded
vessel loops. Actual participant-marked distances were compared to the assigned
distances followed by Bland-Altman plots and linear regression analysis to
determine accuracy and proportional error trends. Study data were further
compared to available data sets from previously published studies. RESULTS:
Laparoscopy measurements were significantly shorter than required (difference
33.8 +/- 28.7 cm, P < 0.001, 95% CI 17.8-49.7). The measuring error was
proportional to the length of the measured segment (63% of the required
distances, IQR 58.9-79.0%, P = 0.02). At laparotomy, mean difference and standard
deviation were lower (1.5 cm +/- SD 15 cm) and not statistically significant (P =
0.7). Re-analysis of previously published data sets validated the observed errors
in laparoscopic bowel measurement (P < 0.01). CONCLUSIONS: Small bowel length
assessment during laparoscopy is inaccurate and associated with substantial
variability. There is a need to develop a standardized laparoscopic technique for
measuring small bowel length which is simple, reproducible, and easy to learn.
PMID- 28409381
TI - DASH-type cryptochromes regulate fruiting body development and secondary
metabolism differently than CmWC-1 in the fungus Cordyceps militaris.
AB - Cryptochromes (CRYs) belong to the photolyase/cryptochrome flavoprotein family,
which is widely distributed in all kingdoms. A phylogenetic analysis indicated
that three Cordyceps militaris proteins [i.e., cryptochrome DASH (CmCRY-DASH), (6
4) photolyase, and cyclobutane pyrimidine dimer (CPD) class I photolyase] belong
to separate fungal photolyase/cryptochrome subfamilies. CmCRY-DASH consists of
DNA photolyase and flavin adenine dinucleotide-binding domains, with RGG repeats
in a C-terminal extension. Considerably, more carotenoids and cordycepin
accumulated in the DeltaCmcry-DASH strain than in the wild-type or DeltaCmwc-1
strains, indicating an inhibitory role for CmCRY-DASH in these biosynthetic
pathways. Fruiting body primordia could form in the DeltaCmcry-DASH strain, but
the fruiting bodies were unable to elongate normally, differently from the Cmwc-1
disruption strain, where primordium differentiation did not occur. Cmcry-DASH
expression is induced by light in the wild-type strain, but not in the DeltaCmwc
1 strain. CmCRY-DASH is also necessary for the expression of Cmwc-1, implying
that Cmcry-DASH and Cmwc-1 exhibit interdependent expression. The Cmvvd
expression levels in the wild-type and DeltaCmcry-DASH strains increased
considerably following irradiation, while Cmvvd expression in the DeltaCmwc-1
strain was not induced by light. It is speculated that the photo adaptation may
be faster in the Cmcry-DASH mutant based on Cmvvd transcript dynamics. These
results provide new insights into the biological functions of fungal DASH CRYs.
Furthermore, the DASH CRYs may regulate fruiting body development and secondary
metabolism differently than WC-1.
PMID- 28409380
TI - Bacterial thiol oxidoreductases - from basic research to new antibacterial
strategies.
AB - The recent, rapid increase in bacterial antimicrobial resistance has become a
major public health concern. One approach to generate new classes of
antibacterials is targeting virulence rather than the viability of bacteria.
Proteins of the Dsb system, which play a key role in the virulence of many
pathogenic microorganisms, represent potential new drug targets. The first part
of the article presents current knowledge of how the Dsb system impacts function
of various protein secretion systems that influence the virulence of many
pathogenic bacteria. Next, the review describes methods used to study the
structure, biochemistry, and microbiology of the Dsb proteins and shows how these
experiments broaden our knowledge about their function. The lessons gained from
basic research have led to a specific search for inhibitors blocking the Dsb
networks.
PMID- 28409382
TI - Yeast response and tolerance to benzoic acid involves the Gcn4- and Stp1
regulated multidrug/multixenobiotic resistance transporter Tpo1.
AB - The action of benzoic acid in the food and beverage industries is compromised by
the ability of spoilage yeasts to cope with this food preservative. Benzoic acid
occurs naturally in many plants and is an intermediate compound in the
biosynthesis of many secondary metabolites. The understanding of the mechanisms
underlying the response and resistance to benzoic acid stress in the eukaryotic
model yeast is thus crucial to design more suitable strategies to deal with this
toxic lipophilic weak acid. In this study, the Saccharomyces cerevisiae multidrug
transporter Tpo1 was demonstrated to confer resistance to benzoic acid. TPO1
transcript levels were shown to be up-regulated in yeast cells suddenly exposed
to this stress agent. This up-regulation is under the control of the Gcn4 and
Stp1 transcription factors, involved in the response to amino acid availability,
but not under the regulation of the multidrug resistance transcription factors
Pdr1 and Pdr3 that have binding sites in TPO1 promoter region. Benzoic acid
stress was further shown to affect the intracellular pool of amino acids and
polyamines. The observed decrease in the concentration of these nitrogenous
compounds, registered upon benzoic acid stress exposure, was not found to be
dependent on Tpo1, although the limitation of yeast cells on nitrogenous
compounds was found to activate Tpo1 expression. Altogether, the results
described in this study suggest that Tpo1 is one of the key players standing in
the crossroad between benzoic acid stress response and tolerance and the control
of the intracellular concentration of nitrogenous compounds. Also, results can be
useful to guide the design of more efficient preservation strategies and the
biotechnological synthesis of benzoic acid or benzoic acid-derived compounds.
PMID- 28409383
TI - Functional analysis of arabinofuranosidases and a xylanase of Corynebacterium
alkanolyticum for arabinoxylan utilization in Corynebacterium glutamicum.
AB - Xylooligosaccharides (XOSs) and arabinoxylooligosaccharides (AXOSs) are major
oligosaccharides derived from arabinoxylan. In our previous report,
Corynebacterium glutamicum was engineered to utilize XOSs by introducing
Corynebacterium alkanolyticum xyloside transporter and beta-xylosidase. However,
this strain was unable to consume AXOSs due to the absence of alpha-L
arabinofuranosidase activity. In this study, to confer AXOS utilization ability
on C. glutamicum, two putative arabinofuranosidase genes (abf51A and abf51B) were
isolated from C. alkanolyticum by the combination of degenerate PCR and genome
walking methods. Recombinant Abf51A and Abf51B heterologously expressed in
Escherichia coli showed arabinofuranosidase activities toward 4-nitrophenyl-alpha
L-arabinofuranoside with k cat values of 150 and 63, respectively, with optimum
at pH 6.0 to 6.5. However, Abf51A showed only a slight activity toward AXOSs and
was more susceptible to product inhibition by arabinose and xylose than Abf51B.
Introduction of abf51B gene into the C. glutamicum XOS-utilizing strain enabled
it to utilize AXOSs as well as XOSs. The xylI gene encoding a putative xylanase
was found upstream of the C. alkanolyticum xyloside transporter genes. A signal
peptide was predicted at the N-terminus of the xylI-encoding polypeptide, which
indicated XylI was a secreted protein. Recombinant mature XylI protein
heterologously expressed in E. coli showed a xylanase activity toward xylans from
various plant sources with optimum at pH 6.5, and C. glutamicum recombinant
strain expressing native XylI released xylose, xylobiose, xylotriose, and arabino
xylobiose from arabinoxylan. Finally, introduction of the xylI gene into the C.
glutamicum AXOS-utilizing strain enabled it to directly utilize arabinoxylan.
PMID- 28409384
TI - Microbial response to environmental stresses: from fundamental mechanisms to
practical applications.
AB - Environmental stresses are usually active during the process of microbial
fermentation and have significant influence on microbial physiology.
Microorganisms have developed a series of strategies to resist environmental
stresses. For instance, they maintain the integrity and fluidity of cell
membranes by modulating their structure and composition, and the permeability and
activities of transporters are adjusted to control nutrient transport and ion
exchange. Certain transcription factors are activated to enhance gene expression,
and specific signal transduction pathways are induced to adapt to environmental
changes. Besides, microbial cells also have well-established repair mechanisms
that protect their macromolecules against damages inflicted by environmental
stresses. Oxidative, hyperosmotic, thermal, acid, and organic solvent stresses
are significant in microbial fermentation. In this review, we summarize the modus
operandi by which these stresses act on cellular components, as well as the
corresponding resistance mechanisms developed by microorganisms. Then, we discuss
the applications of these stress resistance mechanisms on the production of
industrially important chemicals. Finally, we prospect the application of systems
biology and synthetic biology in the identification of resistant mechanisms and
improvement of metabolic robustness of microorganisms in environmental stresses.
PMID- 28409385
TI - The effect of dietary folic acid on biochemical parameters and gene expression of
three heat shock proteins (HSPs) of blunt snout bream (Megalobrama amblycephala)
fingerling under acute high temperature stress.
AB - The effects of dietary folic acid on biochemical parameters and gene expression
of three heat shock proteins (HSPs) of blunt snout bream (Megalobrama
amblycephala) fingerling under acute high temperature stress. Six dietary folic
acid groups (0.0, 0.5, 1.0, 2.0, 5.0, and 10.0) mg/kg diets were designed and
assigned into 18 tanks in three replicates each (300 l/tank) and were
administered for 10 weeks in a re-circulated water system. The fingerlings with
an initial weight of 27.0 +/- 0.03 g were fed with their respective diets four
times daily. At the end of the experiment, samples were collected before
challenge, 0, 24, 72 h, and 7 days. Serum total protein (TP), alanine
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), cortisol, glucose, complement C3 (C3), complement C4 (C4, immunoglobulin M
(IgM) hepatic superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA),
and the expression of heat shock protein 60 (HSP60), 70 (HSP70), and 90 (HSP90)
were studied. The results showed that fish fed with dietary folic acid between
1.0, 2.0, and 5.0 mg/kg significantly (P < 0.05) increased serum TP, C3, C4
hepatic SOD, CAT, and the expression of HSP60, HSP70, and HSP90 before and after
temperature challenge of 32 degrees C. Also, serum ALP, cortisol, glucose, and
hepatic MDA were significantly (P < 0.05) reduced by supplementation of dietary
folic acid level 1.0, 2.0, and 5.0 mg/kg before and after the same temperature
challenge of 32 degrees C. Before stress, 0, 24, 72 h, and 7 days significantly
(P < 0.05) affects serum biochemical parameters, immune and antioxidant
capacities, and expression level of three HSPs. Furthermore, there was no
statistical evidence to show that dietary folic acid inclusion level and
temperature duration have significant interactive effect on serum biochemical
parameters, antioxidant parameters, and gene expression level (P > 0.05) of the
three HSPs. However, there were statistical significant interactive effect
between dietary folic acid inclusion level and temperature duration on serum C3
and C4 (P < 0.05) except IgM (P > 0.05). The present results indicate that
supplementation of basal diet from 1.0 mg/kg; 2.0 and 5.0 mg/kg can enhance acute
high temperature resistance ability in M. amblycephala fingerling to some degree
and improve physiological response, immune and antioxidant capacities, and
expression level of three HSPs.
PMID- 28409386
TI - Nocturnal oviposition behavior of blowflies (Diptera: Calliphoridae) in the
southern hemisphere (South Africa and Australia) and its forensic implications.
AB - Published research has offered contradictory evidence of the occurrence of
nocturnal oviposition by carrion-breeding blowflies, a behavior that can affect
the interpretation of forensic estimates of a minimum post mortem interval
(minPMI) by up to 12 hours, depending on latitude and season. The majority of
published studies are from the northern hemisphere. Field experiments were
conducted in South Africa and Australia that extend observations to species of
the southern hemisphere. Various vertebrate carrion was exposed at night in
summer under different lunar phases and/or artificial lighting, and in woodland
and pasture areas. Three laboratory experiments were also conducted. No nocturnal
oviposition occurred outdoors in Berry, Australia, but Lucilia cuprina, Lucilia
sericata and Chrysomya megacephala laid eggs outdoors at night in Grahamstown and
Durban, South Africa. In laboratory experiments L. sericata, L. cuprina,
Chrysomya chloropyga and Chrysomya putoria laid eggs and Calliphora augur
deposited larvae under nocturnal conditions. Chrysomya albiceps and C. chloropyga
laid eggs in darkness with increasing likelihood as ambient temperature
increased. This study shows that nocturnal ovi/larviposition by carrion-breeding
blowflies is possible in both South Africa and Australia. The forensic issue is
therefore not whether nocturnal oviposition occurs, but rather whether the
conditions of a particular case are more or less conducive to it. Circadian
rhythms and physiological thresholds (particularly temperature and humidity)
appear to act individually and in conjunction to stimulate or inhibit nocturnal
laying. The significance of carcass size, freezing and handling of carcasses and
comprehensive quantification for experimental design is discussed, and
recommendations are made for future laboratory and case scene experiments.
PMID- 28409387
TI - Fatal abdominal injuries in a bicycle-pedestrian collision - Reconstruction using
multibody simulation.
AB - Fatal bicycle-pedestrian collisions do not occur frequently and thus are rarely
reported in literature. Pedestrians in bicycle-pedestrian accidents often sustain
severe craniocerebral injuries caused by a collision induced fall with head
impact on the road surface. We describe a case where a pedestrian crossing a road
was hit by a bicycle. Hematomas of the left lower leg and of the left
flank/abdomen were found to be caused by the primary impact. However, the fatal
injuries were found to be contralateral with a rupture of the right renal
pedicle, a rupture of the right lobe of the liver and a tear of the vena cava.
Neither the bicycle impact nor a fall onto the road surface could cause these
injuries. Multibody simulation (PC Crash 9.2) revealed entanglement between the
bicyclist and the pedestrian followed by a contact interaction between the
pedestrian laying on the road surface and the falling bicyclist. In forensic case
work post-crash contact interactions between the bicyclist and the pedestrian
should be considered as a potential source of severe injuries.
PMID- 28409388
TI - Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and
hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis.
AB - BACKGROUND AND AIM: While diethylcarbamazine citrate (DEC) displays important
anti-inflammatory effects in experimental models of liver injury, the mechanisms
of its action remain poorly understood. The aim of the present study was to
investigate the fibrolytic potential of DEC. METHODS: Mice receive two injections
of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was
administered through drinking water during the last 12 days of liver injury.
RESULTS: The expression of hepatic stellate cells (HSCs) activation markers,
including smooth muscle alpha-actin (alpha-SMA), collagen I, transforming growth
factor-beta 1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue
inhibitor of metalloproteinase-1 (TIMP-1) was assessed. The influence of DEC on
the intracellular MAPK pathways of the HSCs (JNK and p38 MAPK) was also
estimated. DEC inhibited HSCs activation measured as the production of alpha-SMA
and collagen I. In addition, it down regulated the production of TGF-beta1 and
TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC
significantly inhibited the activation of the JNK and p38 MAPK signaling
pathways. CONCLUSIONS: In conclusion, DEC significantly attenuated the severity
of CCl4-induced liver injury and the progression of liver fibrosis, exerting a
potential fibrolytic effect in the CCl4-induced fibrosis model.
PMID- 28409389
TI - Curcumin protects dopaminergic neurons against inflammation-mediated damage and
improves motor dysfunction induced by single intranigral lipopolysaccharide
injection.
AB - Various studies have indicated a lower incidence and prevalence of neurological
conditions in people consuming curcumin. The ability of curcumin to target
multiple cascades, simultaneously, could be held responsible for its
neuroprotective effects. The present study was designed to investigate the
potential of curcumin in minimizing microglia-mediated damage in
lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and
increased inflammatory profile of the CNS have severe behavioral consequences. In
the current investigation, a single injection of LPS (5 ug/5 ul PBS) was injected
into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was
administered daily for a period of 21 days. LPS triggered an inflammatory
response characterized by glial activation [Iba-1 and glial fibrillary acidic
protein (GFAP)] and pro-inflammatory cytokine production (TNF-alpha and IL-1beta)
leading to extensive dopaminergic loss and behavioral abnormality in rats. The
behavioral observations, biochemical markers, quantification of dopamine and its
metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase
(TH) were evaluated after 21 days of LPS injection. Curcumin supplementation
prevented dopaminergic degeneration in LPS-treated animals by normalizing the
altered levels of biomarkers. Also, a significant improvement in TH levels as
well as behavioral parameters (actophotometer, rotarod, beam walking and grid
walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic
neurons against LPS-induced inflammatory response, which was associated with
suppression of glial activation (microglia and astrocytes) and transcription
factor NF-kappaB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed
microglial NADPH oxidase activation as observed from NADPH oxidase activity. The
results suggested that one of the important mechanisms by which curcumin mediates
its protective effects in the LPS-induced PD model is by inhibiting glial
activation. Therefore, curcumin could be a potential therapeutic agent for
inflammation-driven neurodegenerative disorders like PD, and its neuroprotective
role should be explored further.
PMID- 28409390
TI - Dynamin-related protein-1 as potential therapeutic target in various diseases.
AB - Mitochondria can interchange morphology due to their dynamic nature. It can exist
in either fragmented disconnected arrangement or elongated interconnected
mitochondrial networks due to fission and fusion, respectively. The recent
studies have revealed the remarkable and unexpected insights into the
physiological impact and molecular regulation of mitochondrial morphology. The
balance between fission and fusion governs the faith of the cell. The active
targeting of DRP 1 to the outer mitochondrial membrane (OMM) is done by non
GTPase receptor proteins such as mitochondrial fission factor, mitochondrial
fission protein 1 and mitochondrial elongation factor 1. The active targeting of
DRP 1 to OMM leads to the fission of mitochondria. However, the imbalance of DRP
1-dependent mitochondrial fission and modulation of equilibrium of fission and
fusion has been documented to be involved in several cardiovascular and
neurodegenerative disorders. In this review, we are focusing on the active
participation of DRP 1 in various diseases and also the factors responsible for
the activation of DRP 1 for its action.
PMID- 28409391
TI - Anti-inflammatory activity of the functional groups present in Hippophae
rhamnoides (Seabuckthorn) leaf extract.
AB - ETHNO PHARMACOLOGICAL RELEVANCE: The study explores the anti-inflammatory
activity of components present in fractions obtained from leaves of Hippophae
rhamnoides in mouse peritoneal macrophages. AIM OF THE STUDY: Immunomodulators
salvage the immune response by enhancing or reducing its capacity to the required
level. Plant extracts are extensively used as immunomodulators because of their
easy availability, simple methods of preparation and minimum side effects with
maximum efficacy. MATERIALS AND METHODS: The present study was conducted to
assess the immunomodulatory activities of phyto constituents present in
Seabuckthorn leaves. The aqueous-alcoholic leaf extract was subjected to
successive and parallel extraction in the presence of polar and non-polar
solvents for fractionation of compounds. Based on the yield, three fractions were
selected viz. parallel methanol (PM), successive chloroform (SC) and successive
methanol (SM) and screened for in vitro immunomodulatory activities. Peritoneal
macrophages were isolated from Balb/c mice and cultured with or without LPS to
evaluate the immunomodulatory effect of the three fractions on cell viability,
hemolytic activity, nitric oxide (NO) production, cytokine levels, iNOS and COX-2
expressions. RESULTS: The results revealed that none of the three fractions
induced hemolysis. Cells treated with PM fraction significantly suppressed LPS
induced NO production and pro-inflammatory cytokines such as TNF-alpha, IL-6 and
IFN-gamma as compared to SC and SM treatment. The iNOS and COX-2 expressions were
also significantly reduced after treatment with PM fraction. CONCLUSIONS: The
decrease in LPS-induced NO production, pro-inflammatory cytokine secretion, iNOS
and COX-2 expression signifies anti-inflammatory properties of PM fraction
containing tannins, proteins and carbohydrate groups. Hence, this plant-derived
immunomodulator can be used as a therapeutic agent in inflammatory diseases.
PMID- 28409394
TI - CUSA for laparoscopic left colectomy.
PMID- 28409393
TI - Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in
vestibular schwannoma patients: a systematic review.
AB - OBJECTIVE: Repeated controlled studies have revealed that stereotactic
radiosurgery is better than microsurgery for patients with vestibular schwannoma
(VS) <3 cm in need of intervention. In this systematic review we aimed to compare
results from single-fraction stereotactic radiosurgery (SRS) to fractionated
stereotactic radiotherapy (FSRT) for patients with VS. DATA SOURCES AND
ELIGIBILITY CRITERIA: We systematically searched MEDLINE, Web of Science, Embase
and Cochrane and screened relevant articles for references. Publications from
1995 through 2014 with a minimum of 50 adult (>18 years) patients with unilateral
VS, followed for a median of >5 years, were eligible for inclusion. After
screening titles and abstracts of the 1094 identified articles and systematically
reviewing 98 of these articles, 19 were included. INTERVENTION: Patients with
unilateral VS treated with radiosurgery were compared to patients treated with
fractionated stereotactic radiotherapy. RESULTS: No randomized controlled trial
(RCT) was identified. None of the identified controlled studies comparing SRS
with FSRT were eligible according to the inclusion criteria. Nineteen case series
on SRS (n = 17) and FSRT (n = 2) were included in the systematic review. Loss of
tumor control necessitating a new VS-targeted intervention was found in an
average of 5.0% of the patients treated with SRS and in 4.8% treated with FSRT.
Mean deterioration ratio for patients with serviceable hearing before treatment
was 49% for SRS and 45% for FSRT, respectively. The risk for facial nerve
deterioration was 3.6% for SRS and 11.2% for FSRT and for trigeminal nerve
deterioration 6.0% for SRS and 8.4% for FSRT. Since these results were obtained
from case series, a regular meta-analysis was not attempted. CONCLUSION: SRS and
FSRT are both noninvasive treatment alternatives for patients with VS with low
rates of treatment failure in need of rescue therapy. In this selection of
patients, the progression-free survival rates were on the order of 92-100% for
both treatment options. There is a lack of high-quality studies comparing
radiation therapy alternatives for patients with VS. Finally, 19 articles
reported long-term tumor control after SRS, while only 2 articles reported long
term FSRT results, making effect estimates more uncertain for FSRT.
PMID- 28409395
TI - Spinal and corticospinal pathways are differently modulated when standing at the
bottom and the top of a three-step staircase in young and older adults.
AB - PURPOSE: This study investigated the modulation of spinal (group Ia afferents)
and corticospinal pathways when young (22.7 +/- 1.3 years) and older adults (72.2
+/- 7.9 years) stood at the bottom and at the top of a three-step staircase
equipped with force platforms. METHOD: Changes in submaximal H-reflex amplitude
(H 50) and slope of the H-reflex input-output relation (spinal pathway), and in
amplitude of motor-evoked potentials (MEP) triggered by transcranial magnetic
stimulation (corticospinal pathway) at two intensities (1.1* and 1.2* motor
threshold) were recorded in soleus when subjects stood as steady as possible
downstairs and upstairs. The centre of pressure (CoP) excursion was analyzed in
the time and frequency domains in both conditions. RESULTS: Regardless of age,
the mean CoP velocity was greater when standing upstairs (11.1 +/- 3.5 mm s-1)
than downstairs (9.0 +/- 2.3 mm s-1; p = 0.002). The CoP power spectral density
(PSD) in the 0-0.5 Hz band was greater upstairs than downstairs (+18.4%; p =
0.03) whereas PSD in the 2-20Hz frequency band was lesser (-41%) upstairs than
downstairs (p < 0.001), regardless of age. In both groups, the H 50 amplitude (
30.6%; p < 0.001) and slope of H-reflex input-output relation (-10.2%; p = 0.002)
were lesser when standing upstairs than downstairs, whereas no significant
difference was observed in MEP amplitude and silent period between balance
conditions (p > 0.05). CONCLUSION: These results indicate a lower dependence on
spinal pathway to control soleus motor neurones when standing upstairs than
downstairs accompanied by a change in postural control. This suggests that
healthy older adults preserved their ability to adjust postural control to
environmental demands.
PMID- 28409396
TI - Factors influencing the post-exercise hepcidin-25 response in elite athletes.
AB - PURPOSE: The extent to which hepcidin regulation after acute bouts of exercise is
influenced by baseline (resting) concentrations of key iron parameters remains
uncertain. This investigation explored the influence of selected iron parameters
and 25-km race walk time on 3-h post-exercise hepcidin-25 levels in international
level race walkers. METHODS: Twenty-four male race walkers completed a graded
exercise test and a 25-km race-walk trial. Throughout the 25-km race-walk, venous
blood samples were collected pre-exercise, immediately post-exercise, and at 3-h
post-exercise. Blood was analysed for serum ferritin, serum iron, Interleukin-6
(IL-6), and hepcidin-25 concentration. RESULTS: IL-6 and hepcidin-25 increased
(7.6- and 7.5-fold, respectively) in response to the 25-km race-walk trial (both
p < 0.01). Significant individual relationships were evident between 3-h post
exercise hepcidin-25, baseline serum ferritin and serum iron (r > 0.62; p <
0.05). Multiple regression analysis showed that these two iron parameters, in
addition to post-exercise IL-6 concentration and 25-km race-walk time, accounted
for ~77% of the variance in 3-h post-exercise hepcidin-25 (p < 0.01). A median
split by the cohort's baseline serum ferritin concentration (LOW: 58.0 vs. HIGH:
101.8 ug/L; p < 0.01) showed a significant between group difference in the 3-h
post-exercise hepcidin-25 (LOW: 6.0 +/- 3.6 vs. 11.3 +/- 5.4 nM; p = 0.01),
despite no differences in baseline serum iron, post-exercise IL-6, or 25-km race
walk time (all p > 0.05). CONCLUSION: Despite exercise activating numerous
hepcidin regulators, baseline iron status appears to play a dominant role in the
regulation of hepcidin-25 in elite-level athletes subsequent to endurance
exercise.
PMID- 28409397
TI - The effect of high-intensity aerobic interval training on markers of systemic
inflammation in sedentary populations.
AB - PURPOSE: This study examined the effects of high-intensity interval training
(HIIT; 30 s sprint, 4-5 min passive recovery) and prolonged intermittent sprint
training (PIST; 10 s sprint, 2-3 min moderate exercise) on the systemic
inflammatory markers C-reactive protein (CRP) and tumor necrosis factor-alpha
(TNF-alpha), aerobic capacity, and anthropometry in a middle-aged, sedentary
population. METHODS: Fifty-five sedentary adults (age 49.2 +/- 6.1 years) were
randomised into HIIT (n = 20), PIST (n = 21), or a sedentary control group (CTRL
n = 14). HIIT and PIST performed three training sessions per week for 9 weeks on
a cycle ergometer, matched for total high-intensity time, while CTRL continued
normal sedentary behaviours. Pre- and post-intervention testing involved measures
of anthropometry, peak oxygen consumption (VO2peak), and venous blood collection
for analyses of CRP and TNF-alpha. RESULTS: HIIT and PIST increased VO2peak
compared to CTRL (+3.66 +/- 2.23 and 3.74 +/- 2.62 mL kg min-1). A group * time
interaction (p = 0.042) and main effect of time (p = 0.026) were evident for
waist girth, with only HIIT showing a significant reduction compared to CTRL (
2.1 +/- 2.8 cm). TNF-alpha and CRP showed no group * time interaction or time
effect (p > 0.05). CONCLUSIONS: In sedentary individuals, 9 weeks of HIIT or PIST
were effective to improve aerobic capacity; however, only HIIT significantly
reduced waist girth and WHR compared to CTRL. Markers of systemic inflammation
remained unchanged across all groups. Accordingly, for inflammation and VO2peak,
the distribution of sprints and the active or passive recovery periods are
inconsequential provided that total duration of high-intensity efforts is
similar.
PMID- 28409398
TI - Middle cerebral artery blood flow velocity during a 4 km cycling time trial.
AB - PURPOSE: This study sought to describe middle cerebral artery blood flow velocity
(MCAv) during a 4 km cycling time trial, and relate it to different pacing
strategies adopted by participants. METHODS: After familiarisation and a
standardised exercise protocol, 15 male trained cyclists rode a 4 km time trial
on a cycling ergometer. MCAv was assessed via transcranial Doppler ultrasound in
the right hemisphere at resting baseline, and throughout the time trial. Mean
arterial pressure, end-tidal partial pressure of carbon dioxide (PetCO2) and
heart rate were assessed alongside MCAv. Plasma lactate was assessed post time
trial. Data were compared depending upon whether participants completed the time
trial with a positive (first half faster than the last) or negative pacing
profile although there was no difference in the time to completion with either
pacing strategy (positive 344 +/- 23 s, negative 334 +/- 14 s; p = 0.394).
RESULTS: Lower mean MCAv (positive pacing -7.6 +/- 14.2%, negative pacing +21.2
+/- 15.0% compared to resting baseline measures; p = 0.004) and lower PetCO2
(significant interaction p < 0.001) towards the end of the time trial were
observed with positive compared to negative pacing. Heart rate and lactate did
not differ between pacing strategies. CONCLUSIONS: Changes in MCAv appear to
depend on the pacing strategy adopted, with a positive pacing strategy likely to
contribute to a hyperventilatory drop in PetCO2 and subsequent reduction in MCAv.
Although lower cerebral blood flow cannot be directly linked to an inability to
raise or maintain power output during the closing stages of the time trial, this
potential contributor to fatigue is worth further investigation.
PMID- 28409399
TI - Pro-apoptotic signaling induced by Retinoic acid and dsRNA is under the control
of Interferon Regulatory Factor-3 in breast cancer cells.
AB - Breast cancer is one of the most lethal malignancies for women. Retinoic acid
(RA) and double-stranded RNA (dsRNA) are considered signaling molecules with
potential anticancer activity. RA, co-administered with the dsRNA mimic
polyinosinic-polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor
Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program
in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment,
synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in
breast cancer cells. IRF3 activation is mediated by a member of the pathogen
recognition receptors, Toll-like receptor-3 (TLR3), since its depletion abrogates
IRF3 activation by RA/poly(I:C) co-treatment. Besides induction of TRAIL,
apoptosis induced by RA/poly(I:C) correlates with the increased expression of pro
apoptotic TRAIL receptors, TRAIL-R1/2, and the inhibition of the antagonistic
receptors TRAIL-R3/4. IRF3 plays an important role in RA/poly(I:C)-induced
apoptosis since IRF3 depletion suppresses caspase-8 and caspase-3 activation,
TRAIL expression upregulation and apoptosis. Interestingly, RA/poly(I:C)
combination synergizes to induce a bioactive autocrine/paracrine loop of type-I
Interferons (IFNs) which is ultimately responsible for TRAIL and TRAIL-R1/2
expression upregulation, while inhibition of TRAIL-R3/4 expression is type-I IFN
independent. Our results highlight the importance of IRF3 and type-I IFNs
signaling for the pro-apoptotic effects induced by RA and synthetic dsRNA in
breast cancer cells.
PMID- 28409400
TI - Comprehensive assessment of the L-lysine production process from fermentation of
sugarcane molasses.
AB - L-Lysine is an essential amino acid that can be produced by chemical processes
from fossil raw materials, as well as by microbial fermentation, the latter being
a more efficient and environmentally friendly procedure. In this work, the
production process of L-lysine-HCl is studied using a systematic approach based
on modeling and simulation, which supports decision making in the early stage of
process design. The study considers two analysis stages: first, the dynamic
analysis of the fermentation reactor, where the conversion of sugars from
sugarcane molasses to L-lysine with a strain of Corynebacterium glutamicum is
carried out. In this stage, the operation mode (either batch or fed batch) and
operating conditions of the fermentation reactor are defined to reach the maximum
technical criteria. Afterwards, the second analysis stage relates to the
industrial production process of L-lysine-HCl, where the fermentation reactor,
upstream processing, and downstream processing are included. In this stage, the
influence of key parameters on the overall process performance is scrutinized
through the evaluation of several technical, economic, and environmental
criteria, to determine a profitable and sustainable design of the L-lysine
production process. The main results show how the operating conditions, process
design, and selection of evaluation criteria can influence in the conceptual
design. The best plant design shows maximum product yield (0.31 g L-lysine/g
glucose) and productivity (1.99 g/L/h), achieving 26.5% return on investment
(ROI) with a payback period (PBP) of 3.8 years, decreasing water and energy
consumption, and with a low potential environmental impact (PEI) index.
PMID- 28409401
TI - Effect of chunk strength on the performance of children with developmental
dyslexia on artificial grammar learning task may be related to complexity.
AB - There's a long held view that chunks play a crucial role in artificial grammar
learning performance. We compared chunk strength influences on performance, in
high and low topological entropy (a measure of complexity) grammar systems, with
dyslexic children, age-matched and reading-level-matched control participants.
Findings show that age-matched control participants' performance reflected
equivalent influence of chunk strength in the two topological entropy conditions,
as typically found in artificial grammar learning experiments. By contrast,
dyslexic children and reading-level-matched controls' performance reflected
knowledge of chunk strength only under the low topological entropy condition. In
the low topological entropy grammar system, they appeared completely unable to
utilize chunk strength to make appropriate test item selections. In line with
previous research, this study suggests that for typically developing children, it
is the chunks that are attended during artificial grammar learning and create a
foundation on which implicit associative learning mechanisms operate, and these
chunks are unitized to different strengths. However, for children with dyslexia,
it is complexity that may influence the subsequent memorability of chunks,
independently of their strength.
PMID- 28409402
TI - Clinical evaluation of tamsulosin in the relief of lower urinary tract symptoms
in advanced prostate cancer patients.
AB - PURPOSE: To assess the effectiveness and safety of tamsulosin combined with
androgen deprivation therapy (ADT) for lower urinary tract symptoms (LUTS) in
advanced prostate cancer (PC) patients. METHODS: Ninety PC patients with moderate
to-severe LUTS randomized into two groups of 45 each. One group received ADT
(group 1), and the other received ADT plus tamsulosin (group 2) for 24 weeks. The
outcome measures were changes in the International Prostate Symptom Score (IPSS),
IPSS obstructive and irritative subscores, quality of life (QoL), maximum urinary
flow rate (Q max), post-voiding residual (PVR) and prostate-specific antigen
(PSA) from baseline. The treatment response was monitored at 8, 16 and 24 weeks.
RESULTS: Both ADT monotherapy and ADT plus tamsulosin significantly improved
IPSS,QoL score, Q max and PVR at the end of the treatment period. ADT plus
tamsulosin had a greater impact on total IPSS, IPSS obstructive subscore, QoL and
PVR at week 8 and week 16 than ADT monotherapy. Tamsulosin group showed greater
improvement in Q max than ADT group. Significant improvements of IPSS, IPSS
obstructive subscore and QoL were achieved at early treatment stage (week 8) in
group 2, whereas similar improvements were achieved at week 16 in group 1. There
were no significant differences in IPSS, IPSS subscores, QoL and PVR between the
two groups at week 24. CONCLUSIONS: Additional administration of tamsulosin
showed significantly greater and sooner relief in LUTS than ADT monotherapy, with
good acceptability. It is feasible that ADT is used alone after 16-24 weeks of
combination therapy.
PMID- 28409403
TI - Effectiveness of beraprost sodium in maintaining vascular access patency in
patients on hemodialysis.
AB - PURPOSE: Hemodialysis vascular access dysfunction, mostly attributed to
neointimal hyperplasia, is a major cause of morbidity and hospitalization in
patients on hemodialysis. It has been reported that prostaglandin I2 has
pleiotropic effects including anti-platelet, vasodilating, anti-inflammatory, and
anti-atherogenic properties. In addition, several studies have shown that
prostaglandin I2 can inhibit neointimal formation after vascular injury. This
study aimed to investigate the effects of beraprost sodium, an oral synthetic
analog of prostaglandin I2, on vascular access patency in patients on
hemodialysis who experienced primary hemodialysis vascular access failure.
METHODS: Fifty-five patients with end-stage renal disease who were on
hemodialysis were prospectively selected for this study. Twenty-three patients
were assigned to be treated with 120 ug/day of beraprost sodium, while remaining
patients (n = 32) were assigned to a control group. The primary outcome was
primary unassisted vascular access patency at 2 years. RESULTS: The incidence of
primary unassisted patency at 2 years was 83% in the beraprost sodium group and
38% in the control group (p = 0.001). Analysis of covariables indicated that this
effect occurred mainly as a result of beraprost sodium administration. No life
threatening adverse event or severe bleeding was recorded in any of the groups.
CONCLUSIONS: Our data indicated that an oral prostaglandin I2 analog, beraprost
sodium, is effective and safe for the maintenance of vascular access patency in
patients on hemodialysis with primary vascular access failure.
PMID- 28409404
TI - Phenotypic and genotypic identification of hard ticks of the genus Haemaphysalis
(Acari: Ixodidae) in Peninsular Malaysia.
AB - Morphotaxonomy based on phenotypic traits of immature hard ticks (Acari:
Ixodidae) is a skill challenge and has prompted many inexperienced acarologists
to adopt DNA-based methods for identifying and discriminating the species. The
aim of this study is therefore to utilize COI gene for verifying the
morphological status of Haemaphysalis ticks in Peninsular Malaysia. A total of 19
on-host ticks collected from four localities were first identified using specific
illustrated taxonomic keys that lead to the genus of Haemaphysalis. Genotypic
traits of tick species were then verified molecularly based on cytochrome oxidase
subunit I (COI) gene using polymerase chain reaction and direct sequencing.
Clustering analysis was carried out by constructing a phylogenetic tree to
determine the genetic variation and diversity of local Haemaphysalis ticks. Based
on external morphological characterizations, all immature ticks were successfully
identified down to the genus level only. Molecular analysis of the genotypic
using COI gene revealed 16 individuals (84%) as Haemaphysalis hystricis, and
three individuals as H. humerosa with sequence homology of 97-99 and 86-87%,
respectively. Haemaphysalis hystricis were clustered in their respective
monophyletic group in the phylogeny trees with a bootstrap of 100%. Furthermore,
a low intraspecific variation (<0.3%) was observed among Malaysian H. hystricis
but high interspecific value (>15%) recorded. This study morphologically and
molecularly confirms the presence of H. hystricis in Malaysia and the findings
will add value to the existing knowledge in identification of ticks in this
country.
PMID- 28409405
TI - Transgenerational loss and recovery of early learning ability in foraging
predatory mites.
AB - The ability to learn is ubiquitous in animals but highly variable within and
between species, populations and individuals. Diet-related circumstances, such as
diet quantity and quality can influence both long-term constitutive (genetic; by
selection) and short-term operational (non-genetic; by the immediate
circumstances) learning performance. Here, we scrutinized the causes of loss of
learning ability, following multi-generational feeding on pollen, in a line of
the predatory mite Amblyseius swirskii, which was previously well able to learn
prey during early life, enhancing foraging later in life. We investigated
whether, and, if so, how quickly, a transgenerational diet switch to live prey
restores the early learning ability of foraging predatory mites. The first
experiment shows that the early learning ability was restored after switching the
diet of the pollen-fed predator line to live spider mites for two generations
before conducting the behavioral assay. The second experiment reveals that
offspring regained their learning ability if the diet of their mothers was
switched from pollen to spider mites for 3 or 10 days before offspring
production. Both experiments in concert suggest transgenerational, pollen-induced
operational loss of learning ability in the predatory mite A. swirskii.
Maternally-transmitted nutrient deficiency and/or maternally-induced epigenetic
changes are the most plausible explanations for the pollen diet-induced loss of
learning ability. Our study represents a key example for maternal diet-induced
variation in learning ability.
PMID- 28409406
TI - Using compensating variation to measure the costs of child disability in the UK.
AB - The objective of disability policy is to create a society where people with
disabilities and their families enjoy an equal standard of living to those
without disabilities, though evidence to underpin policy is sparse. We defined
the compensating variation (CV) of child disability as the amount of additional
income a family with a disabled child would require to achieve the same living
standards as a similar family without a disabled child. The aims of this study
were to estimate the CV for child disability and to explore how this varied for
different levels of disability and reference levels of living standards. Using
data on 54,641 families from the Family Resources Survey (2004-2012), we matched
families with (cases) and without (controls) a disabled child on family and child
characteristics plus living standards and calculated the income difference
inclusive of disability benefits. Our findings suggest that across families with
the most disabled children, a compensating variation equal to an extra L56-L79 a
week was required to achieve the same living standards as matched families
without a disabled child compared with the mean level of state disability benefit
L47-L71 a week in this group.
PMID- 28409407
TI - Associations Between Dopamine D2 Receptor (DRD2) Gene, Maternal Positive
Parenting and Trajectories of Depressive Symptoms from Early to Mid-Adolescence.
AB - Using data from the Longitudinal Study of Chinese Children and Adolescents
(LSCCA), this study is the first to examine the roles of the dopamine D2 receptor
(DRD2) gene polymorphisms (i.e., TaqIA and A241G) and maternal positive parenting
at ages 10 and 11 years in the trajectories of depressive symptoms from early to
mid-adolescence (ages 11 to 16 years). In a sample of 1090 Chinese adolescents
(50% girls), three trajectories of depressive symptoms were identified: (i) low
stable (36.1%), (ii) moderate-increasing (44.5%), and (iii) high-increasing
(19.4%). A241G AA homozygotes and youth exposed to lower levels of maternal
positive parenting were both at increased odds to follow the high-increasing vs.
low-stable trajectory. Moreover, the A241G polymorphism interacted with maternal
positive parenting to distinguish the moderate-increasing trajectory from the
high-increasing and the low-stable trajectories. For A241G G-allele carriers, but
not AA homozygotes, exposure to high quality of maternal parenting decreased the
odds to follow the high-increasing vs. moderate-increasing trajectory of
depressive symptoms. For AA homozygotes, but not G-allele carriers, high quality
of maternal parenting increased the odds to follow the low-stable vs. moderate
increasing trajectory. The DRD2 TaqIA polymorphism had neither a direct nor an
interactive effect with maternal positive parenting on trajectory membership. The
current findings highlight the importance of investigating gene-by-environment
interactions (G * E) in trajectories of depressive symptoms over adolescence, and
support a developmental versus static nature of G * E effects.
PMID- 28409408
TI - Spontaneous recombinase activity of Cre-ERT2 in vivo.
AB - Inducible Cre-ERT recombinase technology is widely used for gene targeting
studies. The second generation of inducible Cre-ERT recombinase, hemizygous
B6.129S-Tg(UBC-cre/ERT2)1Ejb/J (hereafter abbreviated as Cre-ERT2), a fusion of a
mutated estrogen receptor and Cre recombinase, was engineered to be more
efficient and specific than the original Cre-ERT. The putative mechanism of
selective Cre-mediated recombination is Cre sequestration in the cytoplasm in the
basal state with translocation to the nucleus only in the presence of tamoxifen.
We utilized both a reporter mouse (B6.129 (Cg)-Gt(ROSA)26Sor tm4(ACTB-tdTomato,
EGFP)Luo /J) and endothelin converting enzyme-1 floxed transgenic mouse line to
evaluate Cre-ERT2 activity. We observed spontaneous Cre activity in both
settings. Unintended Cre activity is a confounding factor that has a potentially
large impact on data interpretation. Thus, it is important to consider background
Cre activity in experimental design.
PMID- 28409409
TI - Hypoglycemic and Hypolipidemic Effects of Leucine, Zinc, and Chromium, Alone and
in Combination, in Rats with Type 2 Diabetes.
AB - For the increasing development of diabetes, dietary habits and using appropriate
supplements can play important roles in the treatment or reduction of risk for
this disease. The objective of this study was to investigate the effects of
leucine (Leu), zinc (Zn), and chromium (Cr) supplementation, alone or in
combination, in rats with type 2 diabetes (T2D). Seventy-seven adult male Wistar
rats were randomly assigned in 11 groups, using nutritional supplements and
insulin (INS) or glibenclamide (GLC). Supplementing Leu significantly reduced
blood glucose, triglycerides (TG), nonesterified fatty acids (NEFA), low-density
lipoprotein (LDL), and increased high-density lipoprotein (HDL) concentrations
compared to vehicle-treated T2D animals, and those improvements were associated
with reduced area under the 2-h blood glucose response curve (AUC).
Supplementation of T2D animals with Zn improved serum lipid profile as well as
blood glucose concentrations but was not comparable with the INS, GLC, and Leu
groups. Supplementary Cr did not improve blood glucose and AUC in T2D rats,
whereas it reduced serum TG and LDL and increased HDL concentrations. In
conclusion, supplementation of diabetic rats with Leu was more effective in
improving blood glucose and consequently decreasing glucose AUC than other
nutritional supplements. Supplementary Zn and Cr only improved serum lipid
profile. The combination of the nutritional supplements did not improve blood
glucose level. Nevertheless, supplementation with Leu-Zn, Leu-Cr, Zn-Cr, and Leu
Zn-Cr led to an improved response in serum lipid profile over each supplement
given alone.
PMID- 28409410
TI - Synergistic Cardioprotective Effects of Combined Chromium Picolinate and
Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on
Some Biochemical Markers.
AB - Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic
heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and
lipid homeostasis. The aim of this study was to evaluate the protective effects
of combined chromium picolinate (CrPic) and atorvastatin treatment against
hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided
into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal
injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group
II). Treatment of hyperlipidemic rats was induced by daily administration of
CrPic at a dose of 200 MUg/kg b.w/day (group III), atorvastatin at a dose of 10
mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7
days. At the end of experiment, serum and heart tissues were obtained.
Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum
dyslipidemia, increased atherogenic indices, and values of ischemia-modified
albumin. In addition to increased values of proprotein convertase
subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A
reductase enzyme and high relative expression levels of pentraxin-3 were
observed. However, paraoxonase-1 activity was markedly decreased in the
hyperlipidemic group. Significant improvement in all assessed parameters was
observed in the rat group treated with both CrPic and atorvastatin. It can be
concluded that combined CrPic and atorvastatin treatments had synergistic
cardioprotective effects against hyperlipidemia which may be through modulating
atherosclerosis as well as cardiac and aortic damage and/or activation of anti
inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.
PMID- 28409411
TI - Attenuating Effect of Zinc and Vitamin E on the Intestinal Oxidative Stress
Induced by Silver Nanoparticles in Broiler Chickens.
AB - Silver nanoparticles (AgNPs) have been increasingly used as antimicrobial and
disinfectant. However, intestinal model studies have shown that AgNPs induce
oxidative stress. Hence, this study aims to investigate the effects of dietary
supplemental zinc (Zn) and vitamin E (VE; alpha-tocopherol acetate) on
attenuating AgNP-induced intestinal oxidative stress in broiler chickens. The
chickens were divided into two groups as follows: (1) control group fed with a
corn-soybean meal basal diet and (2) nano group, received drinking water
containing 1000 mg/kg AgNPs. All the nano-exposed birds were divided into six
dietary treatment groups, namely, the basal diets supplemented with (1) 60 mg/kg
Zn as ZnSO4, (2) 120 mg/kg Zn, (3) 100 mg/kg VE, (4) 200 mg/kg VE, (5) 60 mg/kg
Zn and 100 mg/kg VE, and (6) 120 mg/kg Zn and 200 mg/kg VE. Results showed that
the AgNPs significantly reduced the body weights of the broilers after 42 days of
oral administration of AgNPs (P < 0.05), and this effect was not alleviated by
any of the dietary treatments. The activity of superoxide dismutase (CuZn-SOD)
increased in all the AgNP-treated birds (P < 0.05); however, CuZn-SOD did not
increase in birds fed with basal diet supplemented with 200 mg/kg VE. In this
treatment, the VE exerted an antioxidant effect to prevent the activation of the
CuZn-SOD enzyme. Furthermore, supplementing Zn increased the activities of
catalase and glutathione peroxidase in the jejunal mucosa (P < 0.05), which were
accompanied with increased malondialdehyde levels (P < 0.05) in the broilers.
AgNP exposure resulted in a significant messenger RNA (mRNA) upregulation of toll
like receptor 4 (TLR4) and TLR2-1 in the jejunal mucosa (P < 0.05). However,
supplemental ZnVE did not reduce TLRs' mRNA expression, except for the diminished
TLR2-1 mRNA levels in birds fed with basal diet supplemented with 120 mg/kg Zn
and 200 mg/kg VE. We concluded that although dietary Zn and VE supplementation
did not attenuate growth depression effect of AgNP, it however attenuates
intestinal oxidative stress in AgNP-treated broiler chickens.
PMID- 28409412
TI - Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review.
AB - PURPOSE OF THE REVIEW: This review will provide an overview of the microcephalic
primordial dwarfism (MPD) class of disorders and provide the reader comprehensive
clinical review with suggested care guidelines for patients with microcephalic
osteodysplastic primordial dwarfism, type II (MOPDII). RECENT FINDINGS: Over the
last 15 years, significant strides have been made in the diagnosis, natural
history, and management of MOPDII. MOPDII is the most common and well described
form of MPD. The classic features of the MPD group are severe pre- and postnatal
growth retardation, with marked microcephaly. In addition to these features,
individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal
dentition, and an increased risk for cerebrovascular disease and insulin
resistance. Biallelic loss-of-function mutations in the pericentrin gene cause
MOPDII, which is inherited in an autosomal recessive manner.
PMID- 28409413
TI - Impact of ammonium nitrate and sodium nitrate on tadpoles of Alytes obstetricans.
AB - The presence of pesticides, herbicides and fertilisers negatively affect aquatic
communities in general, and particularly amphibians in their larval phase, even
though sensitivity to pollutants is highly variable among species. The Llobregat
Delta (Barcelona, Spain) has experienced a decline of amphibian populations,
possibly related to the reduction in water quality due to the high levels of
farming activity, but also to habitat loss and alteration. We studied the effects
of increasing ammonium nitrate and sodium nitrate levels on the survival and
growth rate of Alytes obstetricans tadpoles under experimental conditions. We
exposed larvae to increasing concentrations of nitrate and ammonium for 14 days
and then exposed them to water without pollutants for a further 14 days. Only the
higher concentrations of ammonium (>33.75 mg/L) caused larval mortality. The
growth rate of larvae was reduced at >=22.5 mg/L NH4+, although individuals
recovered and even increased their growth rate once exposure to the pollutant
ended. The effect of nitrate on growth rate was detected at >=80 mg/L
concentrations, and the growth rate reduction in tadpoles was even observed
during the post-exposure phase. The concentrations of ammonium with adverse
effects on larvae are within the range levels found in the study area, while the
nitrate concentrations with some adverse effect are close to the upper range
limit of current concentrations in the study area. Therefore, only the presence
of ammonium in the study area is likely to be considered of concern for the
population of this species, even though the presence of nitrate could cause some
sublethal effects. These negative effects could have an impact on population
dynamics, which in this species is highly sensitive to larval mortality due to
its small clutch size and prolonged larval period compared to other anuran
amphibians.
PMID- 28409414
TI - Survival and development of bullfrog tadpoles in microcosms treated with
abamectin.
AB - As compared to other aquatic taxonomic groups, few studies have been conducted so
far evaluating the potential risks of pesticides to amphibians. Furthermore, most
existing studies with amphibians consist of acute laboratory toxicity tests that
mostly only evaluated single peak pesticide exposure. In the present study,
potential chronic effects of single and repeated abamectin applications on the
survival and development of L. catesbeianus tadpoles under (semi-) field
conditions were evaluated. To this end, tadpoles were housed in microcosms
treated with single or repeated applications of abamectin (as the commercial
product Vertimec(r) 18 EC). The single application level corresponded to the
previously established laboratory 96 h LC50 of the test organism, whereas the
repeated application was based on abamectin concentrations likely to occur in
runoff water from agricultural areas where Vertimec(r) 18 EC is applied. Under
semi-field conditions, toxicity after the single application was greater than
would be expected from the laboratory toxicity value. Although the repeated
application did not exert direct effects on tadpole survival, the observed delay
in development may have pronounced effect on the fitness and survival of anuran
populations in edge-of-field water bodies.
PMID- 28409415
TI - gamma-aminobutyric acid (GABA) confers chromium stress tolerance in Brassica
juncea L. by modulating the antioxidant defense and glyoxalase systems.
AB - Chromium (Cr) toxicity is hazardous to the seed germination, growth, and
development of plants. gamma-aminobutyric acid (GABA) is a non-protein amino acid
and is involved in stress tolerance in plants. To investigate the effects of GABA
in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.)
seedlings with Cr (0.15 and 0.3 mM K2CrO4, 5 days) alone and in combination with
GABA (125 uM) in a semi-hydroponic medium. The roots and shoots of the seedlings
accumulated Cr in a dose-dependent manner, which led to an increase in oxidative
damage [lipid peroxidation; hydrogen peroxide (H2O2) content; superoxide (O2*-)
generation; lipoxygenase (LOX) activity], methylglyoxal (MG) content, and
disrupted antioxidant defense and glyoxalase systems. Chromium stress also
reduced growth, leaf relative water content (RWC), and chlorophyll (chl) content
but increased phytochelatin (PC) and proline (Pro) content. Furthermore,
supplementing the Cr-treated seedlings with GABA reduced Cr uptake and
upregulated the non-enzymatic antioxidants (ascorbate, AsA; glutathione, GSH) and
the activities of the enzymatic antioxidants including ascorbate peroxidase
(APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR),
glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase
(SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II), and
finally reduced oxidative damage. Adding GABA also increased leaf RWC and chl
content, decreased Pro and PC content, and restored plant growth. These findings
shed light on the effect of GABA in improving the physiological mechanisms of
mustard seedlings in response to Cr stress.
PMID- 28409417
TI - How Nucleus Mechanics and ECM Microstructure Influence the Invasion of Single
Cells and Multicellular Aggregates.
AB - In order to move in a three-dimensional extracellular matrix, the nucleus of a
cell must squeeze through the narrow spacing among the fibers and, by adhering to
them, the cell needs to exert sufficiently strong traction forces. If the nucleus
is too stiff, the spacing too narrow, or traction forces too weak, the cell is
not able to penetrate the network. In this article, we formulate a mathematical
model based on an energetic approach, for cells entering cylindrical channels
composed of extracellular matrix fibers. Treating the nucleus as an elastic body
covered by an elastic membrane, the energetic balance leads to the definition of
a necessary criterion for cells to pass through the regular network of fibers,
depending on the traction forces exerted by the cells (or possibly passive
stresses), the stretchability of the nuclear membrane, the stiffness of the
nucleus, and the ratio of the pore size within the extracellular matrix with
respect to the nucleus diameter. The results obtained highlight the importance of
the interplay between mechanical properties of the cell and microscopic geometric
characteristics of the extracellular matrix and give an estimate for a critical
value of the pore size that represents the physical limit of migration and can be
used in tumor growth models to predict their invasive potential in thick regions
of ECM.
PMID- 28409416
TI - Tributyltin bioaccumulation and toxic effects in freshwater gastropods Pomacea
canaliculata after a chronic exposure: field and laboratory studies.
AB - Freshwater samples and gastropod mollusks (Pomacea canaliculata) were collected
at 5 sampling stations located along the lower Rio de la Plata basin, Argentina,
to assess the extent of tributyltin (TBT) contamination. Determined data revealed
the presence of TBT and some of its breakdown products (dibutyltin: DBT, and
monobutyltin: MBT) in all freshwater samples and also in soft tissues of P.
canaliculata gastropods. Chronic bioassays (6 months) were performed using female
gastropods that had been reared under laboratory conditions and exposed to a
similar TBT concentration than the value determined in freshwater samples (1 ug L
1). The aims of this study were to evaluate the extent of TBT accumulation, the
tissue distribution, and the effects on selected biomarkers (activity of
superoxide dismutasa: SOD, activity of catalase: CAT, levels of total
glutathione: t-GSH, lipid peroxidation, and activity of acetylcholinesterase:
AChE). Gonads presented the highest accumulation, followed by the cephalopedal
region, albumin gland, and finally hepatopancreas. Both metabolites, DBT and MBT,
were also found. All exposed female animals presented development of a penis
reflecting the potential of TBT as an endocrine disrupting chemical for this
gastropod species. Results on the selected biomarkers confirmed additional
adverse effects induced by TBT. An increase in CAT activity and changes in t-GSH
levels are indicative of alterations on the cellular redox status. The inhibition
of AChE could reflect signs of neurotoxicity. Altogether, these results reveal a
negative impact on the health of this gastropod population.
PMID- 28409418
TI - Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case
control study in the Chinese population.
AB - BACKGROUND: The cysteinyl transfer RNA synthetase gene (CARS) is located on
chromosome band 11p15.5, which is an important tumor-suppressor gene region.
Mutations in CARS have been identified in many kinds of cancers; however,
evidence for a relationship between genetic variants in CARS and gastric cancer
at the population level is still lacking. Thus, we explored the association of
variants in CARS with gastric cancer using a two-stage case-control strategy in
Chinese. METHODS: We undertook a two-stage case-control study to investigate the
association between polymorphisms in CARS and risk of gastric cancer with use of
an Illumina Infinium(r) BeadChip and an ABI 7900 system. RESULTS: Four single
nucleotide polymorphisms (SNPs) were significantly associated with gastric cancer
risk in both the discovery stage and the validation stage after adjustment for
age and sex. In addition, the combined results of the two stages showed these
SNPs were related to gastric cancer risk (P false discovery rate <= 0.001 for
rs384,490, rs729662, rs2071101, and rs7394702). In silico analyses revealed that
rs384490 and rs7394702 could affect transcription factor response elements or DNA
methylation of CARS, and rs729662 was associated with the prognosis of gastric
cancer. Additionally, expression quantitative trait loci analysis showed rs384490
and rs729662 might alter expression of CARS-related genes. CONCLUSIONS: The
potential functional SNPs in CARS might influence the biological functions of
CARS or CARS-related genes and ultimately modify the occurrence and development
of gastric cancer in Chinese. Further large-scale population-based studies or
biological functional assays are warranted to validate our findings.
PMID- 28409419
TI - Spiritual Well-Being and Spiritual Distress in Cancer Patients Undergoing
Chemotherapy: Utilizing the SWBQ as Component of Holistic Nursing Diagnosis.
AB - Holistic nursing care requires attention to the spiritual dimension. This is
particularly important when caring for patients with cancer. This research
presents the results of the assessment of spiritual well-being using the
Spiritual Well-Being Questionnaire (SWBQ) to validate the nursing diagnosis of
spiritual distress. Structured interviews were conducted with 169 patients in one
hospital in Portugal. We concluded that the SWBQ is a useful and reliable
instrument to assess spiritual distress, which highlights the importance of
listening to patients and questioning them about spiritual needs as well as the
importance of differential diagnosis aimed at effective interventions.
PMID- 28409421
TI - The Impact of Microenvironment on the Synovial Sarcoma Transcriptome.
AB - Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and
resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been
compared to its source tumor. In order to compare matched tumor and cell line
pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically
engineered mouse model of SS, as well as 2 pairs from human SS tumors.
Transcriptomes of mouse tumors and derivative cell lines deviated significantly.
Differentially expressed genes highlighted inflammatory infiltrates and
metabolism. The same was found for the human tumor and cell line pairs. More was
shared between different tumors than between any tumor and its cell line. Direct
xenografting generated transcriptomes that more closely resembled the primary
tumor than did its derivative cell line. SS tumor transcriptomes are powerfully
impacted by the environment wherein they reside, especially with regard to immune
interaction and metabolism.
PMID- 28409420
TI - Single fraction spine stereotactic ablative body radiotherapy with volumetric
modulated arc therapy.
AB - This study investigated a single institution's experience with volumetric
modulated arc therapy (VMAT) directed stereotactic ablative body radiotherapy
(SABR) for vertebral metastases. From 2010 to 2014, 95 lesions of spinal
metastases in 73 patients were treated with SABR using VMAT. Clinical local
control, pain level, and use of steroid medication were employed to evaluate
treatment responses. The majority (79%) of patients were treated with a radiation
dose of 20 Gy in a single fraction. However, when normal tissue constraints could
not be achieved, the dose was reduced to 18 Gy (11%) or 16 Gy (8%) in 1 fraction.
At the median follow up of 12.7 months (mean 18.0, range 1-56 months), clinical
local control was 97% (92 out of 95). There was a mean 81% (median 100%, range 28
100%) decrease in subjective pain score. Seventy-seven percent of patients had a
decrease in narcotic pain medication use. Pain was completely resolved at the
treatment site for 69% (66/95) of patients. Prior to the SABR treatment, 33%
(31/95) of patients had epidural extension of tumor. Among patients with epidural
involvement, 45% (14/31) exhibited neurologic impairment prior to treatment.
Twenty-three percent (7/31) experienced spinal cord compression. Prior to
treatment, 34 patients experienced some form of neurologic impairment. Of these
patients, 24% (8/34) experienced improved motor functioning; the remaining 76%
(26/34) of patients' neurological dysfunction were stable. Our results indicate
the SABR regimen using VMAT technique is clinically effective in achieving
clinical local control and palliation. This is the first publication reporting
clinical outcomes of VMAT directed SABR.
PMID- 28409422
TI - Influence of long-term equine herpesvirus type 1 (EHV-1) infection on primary
murine neurons-the possible effects of the multiple passages of EHV-1 on its
neurovirulence.
AB - Equine herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae
subfamily, is a neurotropic virus causing latent infections in the nervous system
of the natural host. In the present study, we have investigated EHV-1 replication
(wild-type Jan-E strain and Rac-H laboratory strain) during long-term infection
and during the passages of the virus in cultured neurons. The studies were
performed on primary murine neurons, which are an excellent in vitro model for
studying neurotropism and neurovirulence of EHV-1. Using real-time cell growth
analysis, we have demonstrated for the first time that primary murine neurons are
able to survive long-term EHV-1 infection. Positive results of real-time PCR test
indicated a high level of virus DNA in cultured neurons, and during long-term
infection, these neurons were still able to transmit the virus to the other
cells. We also compared the neurovirulence of Rac-H and Jan-E EHV-1 strains after
multiple passages of these strains in neuron cell culture. The results showed
that multiple passages of EHV-1 in neurons lead to the inhibition of viral
replication as early as in the third passage. Interestingly, the inhibition of
the EHV-1 replication occurred exclusively in neurons, because the equine dermal
(ED) cells co-cultivated with neuroculture medium from the third passage showed
the presence of large amount of viral DNA. In conclusion, our results showed that
certain balance between EHV-1 and neurons has been established during in vitro
infection allowing neurons to survive long-term infection.
PMID- 28409423
TI - Effect of C/N ratio and microelements on nutrient dynamics and cell morphology in
submerged fermentation of Aspergillus giganteus MTCC 8408 using Taguchi DOE.
AB - This paper is concerned with the effect of individual Na+, K+, Mg2+ and Ca2+ ions
upon the nutrient dynamics and cell morphology during submerged fermentation of
Aspergillus giganteus MTCC 8408 in a medium containing ample soluble starch, corn
steep liquor and proteose peptone supply. Nutrient dynamics was elucidated using
Taguchi's DOE (design of experiment) L8 orthogonal array (OA) with carbon,
nitrogen and four most influensive microelements at their assigned ratio namely;
K+/Ca2+ and Mg2+/Na+. Scanning electron microscopy (SEM) was used to correlate
the effect of selected factors on morphological changes and nutrient dynamics
during submerged fermentation. At higher K+/Ca2+ ratio 4.78:1; the maximum growth
was figured out in terms of dry weight, while the inhibition of dry weight
production was observed at higher Mg2+/Na+ ratio 0.94:1 with enhanced
intracellular afp production. At lower C/N ratio 27.4:1; filamentous form of
growth was maintained with the hyphae being scarcely branched without bulbous
cells. Membrane perturbation due to the induction of intracellular oxidative
stress was noticed at higher C/N ration. Taguchi DOE resulted in afp yield per
substrate utilized, Y p/s of 1.08 mg g-1 soluble starch utilized with gram dry
cell weight (gdcw) of 23.9 g L-1 while afp yield per biomass utilized resulted, Y
p/x of 1.12 mg afp gdcw-1 L-1 and biomass yield per substrate utilized, Y x/s of
1.195 gdcw g-1 L-1. The present study revealed an opportunity to develop a cost
effective methods for cell propagation so as to yield effective inoculum levels
towards mass production and formulation studies.
PMID- 28409424
TI - Enhanced saccharification of lignocellulosic agricultural biomass and increased
bioethanol titre using acclimated Clostridium thermocellum DSM1313.
AB - Consolidated bioprocess assures an efficient lignocellulosic conversion to
fermentable sugars and subsequently to bioethanol. Such a single-step hydrolysis
and anaerobic fermentation was achieved with acclimated Clostridium thermocellum
DSM 1313 on different mildly pre-treated agricultural lignocellulosic residues
without any additional enzymes/and strains. Acclimation was achieved by serially
sub-culturing in increasing concentration of individual substrates, such as rice
husk, sugarcane bagasse, and banana pseudostem in the standard media, with
cellobiose as an adjunct. The acclimated cellulolytic thermophile exhibited an
early log phase entry with enhanced growth compared to the direct inoculation
experiments with unacclimated culture. Around 672 mg/g of reducing sugar was
produced from sugarcane bagasse media and 636 mg/g from rice husk media and 513
mg/g from banana pseudostem media with the acclimated organism. Bioethanol
production also doubled in experiments with serially acclimated cultures, with a
maximum of 1.21 and 1.0 g/L ethanol titre from sugarcane bagasse and rice husk,
respectively. The serial acclimation experiments have increased the
saccharification potentials of the organism towards the respective
lignocellulosic substrates and also enhanced the bioethanol production.
PMID- 28409425
TI - Instant green synthesis of silver-based herbo-metallic colloidal nanosuspension
in Terminalia bellirica fruit aqueous extract for catalytic and antibacterial
applications.
AB - In the present study, microwave-assisted, optimized, instant, Terminalia
bellirica fruit extract-mediated green synthesis of colloidal silver
nanoparticles (AgNPs) has been reported. The synthesized AgNPs were characterized
by UV-Vis spectroscopy, FTIR, Zetasizer, FESEM, EDX and XRD. The characteristic
surface plasmon peak of reaction mixture at 406 nm confirmed the synthesis of
AgNPs. The FTIR studies confirmed phytoconstituents were responsible for the
synthesis and stability of AgNPs. The FESEM, EDX and XRD analysis revealed the
presence of spherical silver nanoparticles of mean diameter <=20.6 nm with face
centered cubic crystalline structure. These AgNPs showed notable catalytic
activity in reduction of 4-nitrophenol to 4-aminophenol in the presence of NaBH4.
The synthesized AgNPs showed potential antibacterial and antibiofilm activity
against bacterial pathogens like Bacillus subtilis, Escherichia coli, Pseudomonas
aeruginosa and Staphylococcus aureus. Thus, these synthesized AgNPs can open
avenues for the development of AgNP-based efficient nanocatalyst and potent
nanomedicine in future.
PMID- 28409426
TI - Ethylenediurea as a potential tool in evaluating ozone phytotoxicity: a review
study on physiological, biochemical and morphological responses of plants.
AB - Present-day climate change scenario has intensified the problem of continuously
increasing ground-level ozone (O3), which is responsible for causing deleterious
effects on growth and development of plants. Studies involving use of
ethylenediurea (EDU), a chemical with antiozonant properties, have given some
promising results in evaluating O3 injury in plants. The use of EDU is especially
advantageous in developing countries which face a more severe problem of ground
level O3, and technical O3-induced yield loss assessment techniques like open-top
chambers cannot be used. Recent studies have detected a hormetic response of EDU
on plants; i.e. treatment with higher EDU concentrations may or may not show any
adverse effect on plants depending upon the experimental conditions. Although the
mode of action of EDU is still debated, it is confirmed that EDU remains confined
in the apoplastic regions. Certain studies indicate that EDU significantly
affects the electron transport chain and has positive impact on the antioxidant
defence machinery of the plants. However, the mechanism of protecting the yield
of plants without significantly affecting photosynthesis is still questionable.
This review discusses in details the probable mode of action of EDU on the basis
of available data along with the impact of EDU on physiological, biochemical,
growth and yield response of plants under O3 stress. Data regarding the effect of
EDU on plant 'omics' is highly insufficient and can form an important aspect of
future EDU research.
PMID- 28409427
TI - Environment polluting conventional chemical control compared to an
environmentally friendly IPM approach for control of diamondback moth, Plutella
xylostella (L.), in China: a review.
AB - The diamondback moth, Plutella xylostella, is recognized as a widely distributed
destructive insect pest of Brassica worldwide. The management of this pest is a
serious issue, and an estimated annual cost of its management has reached
approximately US$4 billion. Despite the fact that chemicals are a serious threat
to the environment, lots of chemicals are applied for controlling various insect
pests especially P. xylostella. An overreliance on chemical control has not only
led to the evolution of resistance to insecticides and to a reduction of natural
enemies but also has polluted various components of water, air, and soil
ecosystem. In the present scenario, there is a need to implement an
environmentally friendly integrated pest management (IPM) approach with new
management tactics (microbial control, biological control, cultural control,
mating disruption, insecticide rotation strategies, and plant resistance) for an
alternative to chemical control. The IPM approach is not only economically
beneficial but also reduces the environmental and health risks. The present
review synthesizes published information on the insecticide resistance against P.
xylostella and emphasizes on adopting an alternative environmentally friendly IPM
approach for controlling P. xylostella in China.
PMID- 28409428
TI - Evaluation of zeolite-supported microscale zero-valent iron as a potential
adsorbent for Cd2+ and Pb2+ removal in permeable reactive barriers.
AB - A new composite adsorbent, zeolite-supported microscale zero-valent iron (Z-mZVI)
was evaluated as a potential adsorbent for the removal of Cd2+ and Pb2+ from
aqueous solution using batch and column experiments. Adsorption isotherms were
well fitted by Langmuir model, and the maximum adsorption capacity was 63.14 mg/g
for Cd2+ and 154.61 mg/g for Pb2+, respectively. Both adsorption processes
followed the pseudo-second-order model which indicated that the rate-limiting
step for different initial concentration was dominated by chemical adsorption
process. The coexistence of Cd2+ and Pb2+ caused the reduction of Cd2+ removal
efficiency, but not for Pb2+. Z-mZVI has a high removal capacity for Cd2+ and
Pb2+ over a wide pH range (3.0-6.8) as well as in the presence of competitive
Ca2+ or Mg2+ ions (<2 mmol/L). Moreover, Z-mZVI shows a high immobilization
capacity for the adsorbed Cd2+ and Pb2+ products, even at the acid solution (pH =
3.95). Column experiment confirmed that Z-mZVI could simultaneously remove Cd2+
and Pb2+ from solution efficiently. Thomas model can simulate the equilibrium
adsorption capacity of Cd2+ and Pb2+ of the Z-mZVI column well. This study
demonstrates that Z-mZVI is an efficient and promising reactive material in
permeable reactive barriers for Cd2+ and Pb2+ removal from aqueous solution.
PMID- 28409429
TI - Multivariate statistical assessment of a polluted river under nitrification
inhibition in the tropics.
AB - A large complex water quality data set of a polluted river, the Tay Ninh River,
was evaluated to identify its water quality problems, to assess spatial
variation, to determine the main pollution sources, and to detect relationships
between parameters. This river is highly polluted with organic substances,
nutrients, and total iron. An important problem of the river is the inhibition of
the nitrification. For the evaluation, different statistical techniques including
cluster analysis (CA), discriminant analysis (DA), and principal component
analysis (PCA) were applied. CA clustered 10 water quality stations into three
groups corresponding to extreme, high, and moderate pollution. DA used only seven
parameters to differentiate the defined clusters. The PCA resulted in four
principal components. The first PC is related to conductivity, NH4-N, PO4-P, and
TP and determines nutrient pollution. The second PC represents the organic
pollution. The iron pollution is illustrated in the third PC having strong
positive loadings for TSS and total Fe. The fourth PC explains the dependence of
DO on the nitrate production. The nitrification inhibition was further
investigated by PCA. The results showed a clear negative correlation between DO
and NH4-N and a positive correlation between DO and NO3-N. The influence of pH on
the NH4-N oxidation could not be detected by PCA because of the very low
nitrification rate due to the constantly low pH of the river and because of the
effect of wastewater discharge with very high NH4-N concentrations. The results
are deepening the understanding of the governing water quality processes and
hence to manage the river basins sustainably.
PMID- 28409430
TI - Spatio-temporal distribution of metals in household dust from rural, semi-urban
and urban environments in the Niger Delta, Nigeria.
AB - Concentrations of metals in household dust samples from rural, semi-urban and
urban zones of the Niger Delta in Nigeria were measured during both 2009 and 2014
with the aim of providing information on changes in the concentrations,
distribution patterns, sources and risks of metals in these zones. The
concentrations of metals in the dust samples were quantified by using inductively
coupled plasma atomic emission spectrophotometry (ICP-AES) after digestion with
aqua regia. The measured concentrations (mg kg-1) of metals in the three zones
within the study periods were as follows: =60 years). Our analysis concluded that the effects of air pollutants on
cardiovascular admissions on dust days were significantly stronger than non-dust
days. The current study strengthens the evidence of effects of air pollution on
health and dust-exacerbated cardiovascular admissions in Lanzhou.
PMID- 28409433
TI - Reusing colored industrial wastewaters in a photofermentation for enhancing
biohydrogen production by using ultrasound stimulated Rhodobacter sphaeroides.
AB - One-time ultrasonication pre-treatment of Rhodobacter sphaeroides was evaluated
for improving biohydrogen production via photofermentation. Batch experiments
were performed by varying ultrasonication amplitude (15, 30, and 45%) and
duration (5, 10, and 15 min) using combined effluents from palm oil as well as
pulp and paper mill as a single substrate. Experimental data showed that
ultrasonication at amplitude 30% for 10 min (256.33 J/mL) achieved the highest
biohydrogen yield of 9.982 mL H2/mLmedium with 5.125% of light efficiency. A
maximum CODtotal removal of 44.7% was also obtained. However, when higher
ultrasonication energy inputs (>256.33 J/mL) were transmitted to the cells,
biohydrogen production did not improve further. In fact, 20.6% decrease of
biohydrogen yield (as compared to the highest biohydrogen yield) was observed
using the most intense ultrasonicated inoculum (472.59 J/mL). Field emission
scanning electron microscope images revealed the occurrence of cell damages and
biomass losses if ultrasonication at 472.59 J/mL was used. The present results
suggested that moderate ultrasonication pre-treatment was an effective technique
to improve biohydrogen production performances of R. sphaeroides.
PMID- 28409435
TI - Aldo-ketoreductase 1 (AKR1) improves seed longevity in tobacco and rice by
detoxifying reactive cytotoxic compounds generated during ageing.
AB - BACKGROUND: Maintenance of seed viability is an important factor for seedling
vigour and plant establishment. Lipid peroxidation mediated reactive carbonyl
compounds (RCC's) and non-enzymatic modifications of proteins through Maillard
and Amadori products reduce seed viability and seedling vigour. RESULTS: In this
study, the relevance of RCCs on genotypic variation in rice seed viability and
overexpression of an aldo-ketoreductase (AKR1) enzyme that detoxify cytotoxic
compounds to improve seed viability and vigour was studied. Physiological and
biochemical approaches were integrated to quantify the variation in seed
viability and seedling vigour in rice genotypes after exposing to ageing
treatment. AKR1 was overexpressed in a susceptible rice genotype and tobacco to
study the relevance of reduced RCC's on seed viability and seedling vigour. The
glycation and lipid peroxidation compounds accumulated after accelerated ageing
treatments in rice genotypes. The accumulation of malondialdehyde, methyl
glyoxal, Maillard and Amadori products affected the seed viability and
germination as they showed a significant negative relationship. The transgenic
rice and tobacco seeds expressing AKR1 showed lower levels of cytotoxic compounds
and glycation products that resulted in improved seed viability and seedling
vigour in rice and tobacco. CONCLUSIONS: The study demonstrates that, reactive
cytotoxic compounds affect the seed viability during storage. Detoxification of
reactive cytotoxic compounds by Aldo-keto reductases is one of the mechanisms to
improve the seed longevity during storage.
PMID- 28409434
TI - The SGIM TEACH Program: A Curriculum for Teachers of Clinical Medicine.
AB - BACKGROUND: Demand for faculty with teaching expertise is increasing as medical
education is becoming well established as a career pathway. Junior faculty may be
expected to take on teaching responsibilities with minimal training in teaching
skills. AIM: To address the faculty development needs of junior clinician
educators with teaching responsibilities and those changing their career focus to
include teaching. SETTING: Sessions at two Society of General Internal Medicine
(SGIM) annual meetings combined with local coaching and online learning during
the intervening year. PARTICIPANTS: Eighty-nine faculty scholars in four
consecutive annual cohorts from 2013 to 2016. PROGRAM DESCRIPTION: Scholars
participate in a full-day core teaching course as well as selective workshops at
the annual meetings. Between meetings they receive direct observation and
feedback on their teaching from a local coach and participate in an online
discussion group. PROGRAM EVALUATION: Sessions were evaluated using a post
session survey. Overall content rating was 4.48 (out of 5). Eighty-nine percent
of participants completed all requirements. Of these, 100% agreed that they had
gained valuable knowledge and skills. DISCUSSION: The TEACH certificate program
provides inexperienced faculty teachers an opportunity to develop core skills.
Satisfaction is high. Future research should focus on the impact that this and
similar programs have on teaching skills.
PMID- 28409436
TI - 9p24 abnormalities in hematologic malignancies with a focus on diffuse large B
cell lymphoma.
PMID- 28409437
TI - Prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating
mononuclear cells in upper tract urothelial carcinoma.
AB - Immunotherapy targeting the programmed death-1 (PD-1) receptor/PD-1 ligand (PD
L1) pathway has shown promising results in several malignancies. However, the
prognostic significance of PD-L1 expression remains unknown in patients with
upper tract urothelial carcinoma (UTUC). This study aimed to evaluate PD-L1
expression and its association with clinicopathological characteristics and
oncological outcomes in UTUC patients. PD-L1 expression on tumor cells and tumor
infiltrating mononuclear cells (TIMCs), and E-cadherin and N-cadherin expression
on tumor cells were assessed by immunohistochemistry in a cohort of 162 patients
with UTUC. Associations of PD-L1 expression on tumor cells and TIMCs with
clinicopathological characteristics and cancer-specific survival (CSS) were
evaluated. Out of 162 patients, 20 (12.3%) and 35 (21.6%) had positive PD-L1
expression on tumor cells and TIMCs, respectively. Decreased E-cadherin
expression was associated with PD-L1 positivity on tumor cells (P = 0.048) and PD
L1 negativity on TIMCs (P = 0.033). PD-L1 expression on tumor cells was higher in
patients with preoperative chronic kidney disease (CKD) stage 4-5 than in those
with no CKD or CKD stage 1-3 (P = 0.011). PD-L1 was differentially expressed in
tumor cells and TIMCs in UTUC. Multivariate analyses revealed that PD-L1
expression on tumor cells independently predicted shorter CSS (P = 0.012),
whereas PD-L1 expression on TIMCs independently predicted longer CSS (P = 0.034).
PMID- 28409438
TI - Emotional intelligence buffers the effect of physiological arousal on dishonesty.
AB - We studied the emotional processes that allow people to balance two competing
desires: benefitting from dishonesty and keeping a positive self-image. We
recorded physiological arousal (skin conductance and heart rate) during a
computer card game in which participants could cheat and fail to report a certain
card when presented on the screen to avoid losing their money. We found that
higher skin conductance corresponded to lower cheating rates. Importantly,
emotional intelligence regulated this effect; participants with high emotional
intelligence were less affected by their physiological reactions than those with
low emotional intelligence. As a result, they were more likely to profit from
dishonesty. However, no interaction emerged between heart rate and emotional
intelligence. We suggest that the ability to manage and control emotions can
allow people to overcome the tension between doing right or wrong and license
them to bend the rules.
PMID- 28409439
TI - Erratum to: Chapter 7 Endothelial Progenitor Cells: Procedure for Cell Isolation
and Applications.
PMID- 28409440
TI - Repair of primary and incisional hernias using composite mesh fixed with
absorbable tackers: preliminary experience of a laparoscopic approach with a
newly designed mesh in 29 cases.
AB - Outcome of primary and incisional hernia repair is still affected by clinical
complications in terms of recurrences, pain and discomfort. Factors like surgical
approach, prosthesis characteristics and method of fixation might influence the
outcome. We evaluated in a prospective observational study a cohort population
which underwent primary and incisional laparoscopic hernia repair, with the use
of a composite mesh in polypropylene fixed with absorbable devices. We focused on
assessing the feasibility and safety of these procedures; they were always
performed by an experienced laparoscopic surgeon, analyzing data from our
patients through the EuraHS registry. Seventy nine procedures of primary and
incisional hernia repair were performed from July 2013 to November 2015 at Santa
Maria Regina degli Angeli Hospital in Adria (RO). All cases have been registered
at the EuraHS registry ( http://www.eurahs.eu ); among them, we analyzed 29
procedures performed using a new composite polypropylene mesh (CMC, Clear
Composite Mesh, DIPROMED srl San Mauro Torinese, Turin, Italy), fixed with
absorbable tackers (ETHICON, Ethicon LLC Guaynabo, Puerto Rico 00969). We
performed 23 incisional hernia repairs, 4 primary hernia repairs (1 umbilical, 2
epigastric and 1 lumbar hernia) and 2 parastomal hernia repairs. The median
operation time was 65.1 min for elective and 81.4 min for urgent procedures
(three cases). We had two post-operative complications (6.89%), one case of
bleeding and another case of prolonged ileus successfully treated with
conservative management. We had no recurrences at follow-up. According to QoL, at
12 months patients do not complain about any pain or discomfort for esthetic
result. Laparoscopic treatment of primary and incisional hernia with the use of
composite mesh in polypropylene fixed with absorbable devices is feasible and
safe.
PMID- 28409441
TI - Isolated rectal cancer surgery: a 2007-2014 population study based on a large
administrative database.
AB - Rectal resection is technically one of the most demanding laparoscopic
procedures, requiring additional training and expertise of both surgeons and
institutions. The literature has shown that laparoscopic procedures can be
appropriate for the treatment of rectal cancer (RC), in terms of safety, outcome
and efficiency, but results may not always be directly transferable to the
general population. This study aimed to investigate the use of laparoscopic
rectal cancer resections in a north-eastern Italian region (the Veneto) and to
see how the characteristics of patients and hospitals are associated with the use
of laparoscopy. This was a retrospective cohort study based on administrative
data collected from 2007 to 2014 in the Veneto region (north-east Italy). In the
period considered (2007-2014), 4953 rectal resections were performed for RC in
Veneto hospitals, accounting for 35% of the total 14,243 surgical procedures
involving the rectum, and resulting in 76,739 days in hospital [mean length of
stay-post-operative (MLOS) 15.5 +/- 11.1 days]. Patients were a mean 67.9 +/-
11.7 years old (68 +/- 12.7 for women, 67.9 +/- 11 for men), while the subgroup
of patients undergoing laparoscopic procedures was on average 2 years younger
(66.5 +/- 11.8 vs 68.8 +/- 11.5; p < 0.05). The four main findings of this study
are: (1) the increasing rates of laparoscopic procedures for RC resection at all
the hospitals in our geographical area, rising up to 52% in 2014. This is
probably related to not only to availability of better equipment but surely to a
growing expertise of surgeons; (2) the esteem of proportion of laparoscopically
treated RC; (3) the significant difference between the laparoscopic and open
surgical approach in terms of mean length of hospital stay after RC resection,
making the laparoscopic approach cost-effective generally speaking; and (4) the
disparities in hospitals' use of laparoscopy by patients' age group: Laparoscopic
surgery is safe also in the elderly population but it is not so widely offers in
Veneto Region hospitals, and it's probably due to the lack of experience about
this approach in frail/old patients.
PMID- 28409442
TI - Surgical management of medullary thyroid carcinoma.
AB - Medullary thyroid cancer (MTC) is a malignant tumor of the parafollicular C cells
of the thyroid and comprises only 1-2% of all thyroid cancer cases. Unlike most
differentiated thyroid cancer, MTC is associated with a mean survival of 8.6
years and accounts for a disproportionate 8.6% of thyroid cancer deaths. Surgery
is the mainstay of treatment for loco-regional disease and the only current means
of cure for MTC. The relatively low incidence of MTC has made the comprehensive
study of this disease difficult and most research to date has been based largely
on single institution, retrospective, and/or non-randomized studies. Despite
various professional organizations such as the American Thyroid Association
establishing guidelines for the diagnosis and treatment of patients with MTC,
there is still significant variation in actual practice patterns with regard to
the extent of surgery, as well as the management of persistent or recurrent
disease. The purpose of this review is to discuss the latest updates in the
surgical treatment of MTC, as well as the management of locally advanced,
recurrent, and metastatic disease based on the most recent data and expert
consensus guidelines.
PMID- 28409443
TI - Role of prophylactic central neck dissection in clinically node-negative
differentiated thyroid cancer: assessment of the risk of regional recurrence.
AB - Prophylactic central neck dissection in clinically node-negative patients remains
controversial. The aim of this multicenter retrospective study was to determine
the rate of metastases in the central neck in clinically node-negative
differentiated thyroid cancer patients, to examine the morbidity, and to assess
the risk of regional recurrence in patients treated with total thyroidectomy with
concomitant bilateral or ipsilateral central neck dissection compared with those
undergoing total thyroidectomy alone. 258 consecutive clinically node-negative
patients were divided into three groups according to the procedures performed:
total thyroidectomy only (group A), total thyroidectomy with concomitant
ipsilateral central neck dissection (group B), and total thyroidectomy combined
with bilateral central neck dissection (group C). Mean operative time and
postoperative stay were shorter in Group A (p < 0.01). The incidence of
postoperative transient hypoparathyroidism was lower in Group A (p = 0.03),
whereas no differences in the incidence of permanent hypoparathyroidism and nerve
palsy were present. Postoperative radioactive iodine administration was higher in
group B and particularly C (p = 0.03) compared with group A. There were no
statistically significant differences in terms of regional recurrence.
Differentiated thyroid cancer has a high rate of central lymph node metastasis
even in clinically node-negative patients; in the present study there was no
statistically significant difference in the rates of locoregional recurrence
between the three modalities of treatment. Total thyroidectomy appears to be an
adequate treatment for clinically node-negative differentiated thyroid cancer.
Prophylactic central neck dissection might be considered for differentiated
thyroid cancer patients with large tumor size or extrathyroidal extension.
PMID- 28409444
TI - Locally invasive thyroid cancer: options for a treatment.
AB - Local invasion to neighbor organs by thyroid cancer is an important
prognosticator and requires different therapeutic approach. Which one is the
possible best treatment option and results are evaluated in this study. A single
institution experience in thyroid cancer invading the airway is evaluated
retrospectively (1990-2016). Facts regarding patients' demographics, disease
history, comorbidities, condition at first evaluation and reason for referral are
analyzed. Hospital records and treatment details are extracted from charts and
Institutional folders. Therapeutic indication and treatment option details are
assessed. A total of 2203 thyroid cancer patients undergoing evaluation and
treatment are found in the Institutional records. According to the current
staging system, T4a cancers are 309. Airway has been compromised in 144 cases.
All patients have been referred after receiving indicative workup imaging or
airway-related symptoms. Well-differentiated histology is reported in 97; non
differentiated pattern is described in the remaining ones. Airway endoscopy is
performed in all patients prior to every treatment planned. In 37 cases, the
airway is found to get benefit from resection with curative intent; stenting has
been indicated in 41 cases while tracheostomy has been performed in 44 cases as
permanent treatment option. Rigid bronchoscopy is apparently a mandatory
preliminary step for patients undergoing resection and reconstruction of a
segmental airway tract. Tracheostomy is performed when the disease could not be
submitted to exeresis or when the tumor biology shows a tumultuous disease. Forty
patients had a stable symptoms relief after stenting. The rate of patients
presenting with respiratory symptoms due to thyroid cancer infiltrating the
airway is decreasing thank to screening programs and the greater attention to
early detection. When possible, the segmental resection and reconstruction of the
compromised airway produces good outcome and represents a surgical subspecialty
requiring a multidisciplinary approach with specific technical competences.
Stenting and tracheotomy are end-stage treatment with possible stable outcome for
highly variable time span.
PMID- 28409445
TI - Ion Mobility Spectrometry - High Resolution LTQ-Orbitrap Mass Spectrometry for
Analysis of Homemade Explosives.
AB - The detailed chemical characterization of homemade explosives (HMEs) and other
chemicals that can mimic or mask the presence of explosives is important for
understanding and improving the performance of commercial instrumentation used
for explosive detection. To that end, an atmospheric-pressure drift tube ion
mobility spectrometry (IMS) instrument has been successfully coupled to a
commercial tandem mass spectrometry (MS) system. The tandem MS system is
comprised of a linear ion trap and a high resolution Orbitrap analyzer. This IMS
MS combination allows extensive characterization of threat chemical compounds,
including HMEs, and complex real-world background chemicals that can interfere
with detection. Here, the composition of ion species originating from a specific
HME, erythritol tetranitrate, has been elucidated using accurate mass
measurements, isotopic ratios, and tandem MS. Gated IMS-MS and high-resolution MS
have been used to identify minor impurities that can be indicative of the HME
source and/or synthesis route. Comparison between data obtained on the IMS/MS
system and on commercial stand-alone IMS instruments used as explosive trace
detectors (ETDs) has also been performed. Such analysis allows better signature
assignments of threat compounds, modified detection algorithms, and improved
overall ETD performance. Graphical Abstract ?.
PMID- 28409446
TI - Isolation of Peroxisomes from Rat Liver and Cultured Hepatoma Cells by Density
Gradient Centrifugation.
AB - Subcellular fractionation is still a valuable technique to unravel organelle
specific proteomes, validate the location of uncharacterized proteins, or to
functionally analyze import and metabolism in individual subcellular
compartments. In this respect, density gradient centrifugation still represents a
very classic, indispensable technique to isolate and analyze peroxisomes. Here,
we present two independent protocols for the purification of peroxisomes from
either liver tissue or the HepG2 hepatoma cell line. While the former permits the
isolation of highly pure peroxisomes suitable for, e.g., subcellular proteomics
experiments, the latter protocol yields peroxisomal fractions from considerably
less purity but allows to easily modify metabolic conditions in the culture
medium or to genetically manipulate the peroxisomal compartment. In this respect,
both purification methods represent alternative tools to be applied in
experiments investigating peroxisome physiology.
PMID- 28409447
TI - Isolation of Peroxisomes from Mouse Brain Using a Continuous Nycodenz Gradient: A
Comparison to the Isolation of Liver and Kidney Peroxisomes.
AB - In the central nervous system (CNS) peroxisomes are present in all cell types,
namely neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells.
Brain peroxisomes are smaller in size compared to peroxisomes from other tissues
and are therefore referred to as microperoxisomes. We have established a
purification procedure to isolate highly purified peroxisomes from the central
nervous system that are well separated from the endoplasmic reticulum and
mitochondria and are free of myelin contamination. The major difficulty in
purification of brain peroxisomes compared to peroxisomes from liver or kidney is
the presence of large amounts of myelin in the CNS, which results in
contamination of the subcellular fractions. Hence, the crucial step of the
isolation procedure is the elimination of myelin by the use of a sucrose
gradient, since without the elimination of myelin no significant enrichment of
purified peroxisomes can be achieved. Another difficulty is that in brain tissue
the abundance of peroxisomes decreases significantly during postnatal
development. We provide a detailed protocol for the isolation of peroxisomes from
mouse central nervous system as well as a protocol for the isolation of
peroxisomes from the liver and kidney using a continuous Nycodenz gradient.
PMID- 28409448
TI - Determining the Topology of Peroxisomal Proteins Using Protease Protection
Assays.
AB - Protease protection assays are powerful tools to determine the topology of
organelle proteins. Their simplicity, together with the fact that they are
particularly suited to characterize endogenous proteins, are their major
advantages and the reason why these assays have been in use for so many years.
Here, we provide a detailed protocol to use with mammalian peroxisomes.
Suggestions on how these assays can be controlled, and how to identify some
technical pitfalls, are also presented.
PMID- 28409449
TI - Isolation of Native Soluble and Membrane-Bound Protein Complexes from Yeast
Saccharomyces cerevisiae.
AB - Immunoprecipitation is a traditional approach to isolate single proteins or
native protein complexes from a complex sample mixture. The original method makes
use of specific antibodies against endogenous proteins or epitope tags, which are
first bound to the target protein and then isolated with protein A beads. An
advancement of this method is the application of a protein A tag fused to the
target protein and the affinity-purification of the tagged protein with human
Immunoglobulin G chemically cross-linked to a sepharose matrix. This method will
be described exemplified by the purification of protein complexes of the
peroxisomal membrane from yeast Saccharomyces cerevisiae.
PMID- 28409450
TI - Method for Measurement of Peroxisomal Very Long-Chain Fatty Acid Beta-Oxidation
and De Novo C26:0 Synthesis Activity in Living Cells Using Stable-Isotope Labeled
Docosanoic Acid.
AB - Peroxisomes are present in virtually every eukaryotic cell type with the
exception of the mature erythrocyte. In higher eukaryotes, one of the main
functions of peroxisomes is lipid metabolism by means of beta-oxidation of very
long-chain fatty acids (VLCFA; >=22 carbon atoms). A dysfunction in peroxisomal
VLCFA beta-oxidation results in elevated VLCFA levels in cells, tissue, and
plasma. Here, we describe a straightforward and sensitive method to measure
peroxisomal beta-oxidation capacity in living cells using stable-isotope labeled
docosanoic acid (D3-C22:0).
PMID- 28409451
TI - Analysis of Plasmalogen Synthesis in Cultured Cells.
AB - Plasmalogen synthesis can be analyzed by metabolic labeling, followed by the
separation of ethanolamine plasmalogens from glycerophospholipids on one
dimensional thin-layer chromatography. The vinyl-ether bond of plasmalogens is
acid-labile, which allows separating plasmalogens as 2-acyl-glycerophospholipids
from diacyl-glycerophospholipids.
PMID- 28409452
TI - Transfection of Primary Human Skin Fibroblasts for Peroxisomal Studies.
AB - Functional studies with primary human skin fibroblasts from patients with a
peroxisomal disorder often require efficient transfection with plasmids to
correct the genetic defect or to express heterologous reporter proteins. Here, we
describe a protocol we commonly use for efficient nonviral transfection of
primary human skin fibroblasts.
PMID- 28409453
TI - siRNA-mediated Silencing of Peroxisomal Genes in Mammalian Cells.
AB - RNAi technologies are a valuable tool in the identification and investigation of
proteins that are involved in peroxisome biogenesis and function. Small
interfering RNA (siRNA) has developed into the most commonly used RNAi tool for
the induction of transient, short-term silencing of protein coding genes.
Although siRNA can induce gene knockdown in a variety of mammalian cell lines,
their utility is limited by efficient uptake of synthetic oligonucleotides into
the cells. Here, we describe different transfection methods that have been
successfully used by us to silence peroxisomal genes in a variety of cell lines,
including primary human skin fibroblasts, which are usually difficult to
transfect.
PMID- 28409454
TI - Dual Reporter Systems for the Analysis of Translational Readthrough in Mammals.
AB - Translational readthrough, the decoding of stop codons as sense codons, leads to
C-terminal extension of proteins which may lead to the formation of protein
isoforms with distinct properties from the original protein. Two proteins have
recently been identified that are targeted to the peroxisome via hidden
peroxisomal targeting signals in their readthrough extensions. This noninduced
basal translational readthrough can be distinguished from pharmacological
induction of readthrough by aminoglycosides or other small molecules, which can
be used for the treatment of diseases caused by premature stop (termination)
codons (PTCs). Readthrough of both, natural stop codons and PTCs, can be
quantified in cell culture using reporter systems. In the present article, we
describe two dual reporter systems, based on combined fluorescence/luminescence
measurement and flow cytometric fluorescence measurement, respectively. Further,
we provide a protocol for a fast and efficient cloning procedure of reporter
constructs. The dual reporter systems described here help to analyze the
peroxisome-specific isoforms of readthrough enzymes as well as potential
readthrough therapeutics.
PMID- 28409455
TI - Cytochemical Detection of Peroxisomes in Light and Electron Microscopy with 3,3'
diaminobenzidine.
AB - Peroxisomes are ubiquitous dynamic and multifunctional organelles that contribute
to numerous anabolic and catabolic pathways, being essential for human health and
development. Their best known functions include the oxidation of fatty acids and
metabolism of hydrogen peroxide with catalase as a marker enzyme. Indeed,
historically, it was the cytochemical staining of catalase in many different
cells and tissues that revealed the ubiquitous presence of peroxisomes in almost
all animal and plant cells. In this chapter, the method for cytochemical staining
of catalase with the alkaline 3, 3'-diaminobenzidine (DAB) is described. Since
aldehyde fixation is a prerequisite for staining of catalase with DAB, a method
for perfusion fixation of rat liver with glutaraldehyde is presented prior to the
cytochemical staining method and the subsequent tissue processing for light and
electron microscopy.
PMID- 28409456
TI - Cryo-Immuno Electron Microscopy of Peroxisomal Marker Proteins.
AB - Electron microscopy samples processed for cryo-immunogold-labeling need to be
gently fixed to keep their antigenicity. Biological material like cultured cells
or tissue can be prepared according to the standard Tokuyasu fixation or in a
further developed rehydration method based on high-pressure freezing. We will
describe here the variant and common steps of both methods in detail and
illustrate their potency in the ultrastructural imaging of peroxisomes.
PMID- 28409457
TI - Detection and Immunolabeling of Peroxisomal Proteins.
AB - Peroxisomes are essential organelles in mammals which contribute to cellular
lipid metabolism and redox homeostasis. The spectrum of their functions in human
health and disease is far from being complete, and unexpected and novel roles of
peroxisomes are being discovered. To date, those include novel biological roles
in antiviral defence, as intracellular signaling platforms and as protective
organelles in sensory cells. Furthermore, peroxisomes are part of a complex
network of interacting subcellular compartments which involves metabolic
cooperation, cross-talk and membrane contacts. As potentially novel peroxisomal
proteins are continuously discovered, there is great interest in the verification
of their peroxisomal localization. Here, we present protocols used successfully
in our laboratory for the detection and immunolabeling of peroxisomal proteins in
cultured mammalian cells. We present immunofluorescence and fluorescence-based
techniques as well as reagents to determine peroxisome-specific targeting and
localization of candidate proteins.
PMID- 28409458
TI - Labeling of Peroxisomes for Live Cell Imaging in the Filamentous Fungus Ustilago
maydis.
AB - The basidiomycete fungus Ustilago maydis has emerged as a powerful model organism
to study fundamental biological processes. U. maydis shares many important
features with human cells but provides the technical advantages of yeast.
Recently, U. maydis has also been used to investigate fundamental processes in
peroxisome biology. Here, we present an efficient yeast recombination-based
cloning method to construct and express fluorescent fusion proteins (or
conditional mutant protein alleles) which target peroxisomes in the fungus U.
maydis. In vivo analysis is pivotal for understanding the underlying mechanisms
of organelle motility. We focus on the in vivo labeling of peroxisomes in U.
maydis and present approaches to analyze peroxisomal motility.
PMID- 28409459
TI - Quantitative Monitoring of Subcellular Redox Dynamics in Living Mammalian Cells
Using RoGFP2-Based Probes.
AB - To gain additional insight into how specific cell organelles may participate in
redox signaling, it is essential to have access to tools and methodologies that
are suitable to monitor spatiotemporal differences in the levels of different
reactive oxygen species (ROS) and the oxidation state of specific redox couples.
Over the years, the use of genetically encoded fluorescent redox indicators with
a ratiometric readout has constantly gained in popularity because they can easily
be targeted to various subcellular compartments and monitored in real time in
single cells. Here we provide step-by-step protocols and tips for the successful
use of roGFP2, a redox-sensitive variant of the enhanced green fluorescent
protein, to monitor changes in glutathione redox balance and hydrogen peroxide
homeostasis in the cytosol, peroxisomes, and mitochondria of mammalian cells.
PMID- 28409460
TI - KillerRed as a Tool to Study the Cellular Responses to Peroxisome-Derived
Oxidative Stress.
AB - Many biological processes and cell fate decisions are modulated by changes in
redox environment. To gain insight into how subcellular compartmentalization of
reactive oxygen species (ROS) formation contributes to (site-specific) redox
signaling and oxidative stress responses, it is critical to have access to tools
that allow tight spatial and temporal control of ROS production. Over the past
decade, the use of genetically encoded photosensitizers has attracted growing
interest of researchers because these proteins can be easily targeted to various
subcellular compartments and allow for controlled release of ROS when excited by
light. This chapter provides guidance and practical advice on the use of po-KR, a
peroxisomal variant of the phototoxic red fluorescent protein KillerRed, to
address fundamental questions about how mammalian cells cope with peroxisome
derived oxidative stress.
PMID- 28409461
TI - Determination of Peroxisomal pH in Living Mammalian Cells Using pHRed.
AB - Organelle pH homeostasis is crucial for maintaining proper cellular function. The
nature of the peroxisomal pH remains somewhat controversial, with several studies
reporting conflicting results. Here, we describe in detail a rapid and accurate
method for the measurement of peroxisomal pH, using the pHRed sensor protein and
confocal microscopy of living mammalian cells. pHRed, a ratiometric sensor of pH,
is targeted to the peroxisomes by virtue of a C-terminal targeting sequence. The
probe has a maximum fluorescence emission at 610 nm while exhibiting dual
excitation peaks at 440 and 585 nm, allowing for ratiometric imaging and
determination of intracellular pH in live cell microscopy.
PMID- 28409462
TI - In Cellulo Approaches to Study Peroxisomal Protein Import - Yeast
Immunofluorescence Microscopy.
AB - Immunofluorescence microscopy is a powerful tool to analyze the localization of
selected proteins in single cells. The technique allows the detection of
endogenously expressed proteins as well as tags added to proteins of choice with
specific antibodies. Originally evolved for human cell lines, protocols are now
also available for yeast cells. Here, we describe an immunofluorescence
microscopy technique for imaging peroxisomal matrix and membrane proteins of the
yeast Saccharomyces cerevisiae.
PMID- 28409463
TI - Blue Native PAGE: Applications to Study Peroxisome Biogenesis.
AB - Blue native polyacrylamide gel electrophoresis (BN-PAGE) is one of the useful
methods to isolate protein complexes including membrane proteins under native
conditions. In BN-PAGE, Coomassie Brilliant Blue G-250 binds to proteins and
provides a negative charge for the electrophoretic separation without denaturing
at neutral pH, allowing the analysis of molecular mass, oligomeric state, and
composition of native protein complexes. BN-PAGE is widely applied to the
characterization of soluble protein complexes as well as isolation of membrane
protein complexes from biological membranes such as the complexes I-V of the
mitochondrial respiratory chain and subcomplexes of the mitochondrial protein
import machinery. BN-PAGE has also been introduced in the field of peroxisome
research, for example, analysis of translocation machinery for peroxisomal matrix
proteins embedded in the peroxisomal membrane. Here, we describe a basic protocol
of BN-PAGE and its application to the study of peroxisome biogenesis.
PMID- 28409464
TI - In Vitro PMP Import Analysis Using Cell-Free Synthesized PMP and Isolated
Peroxisomes.
AB - The Pex19p- and Pex3p-dependent direct import of peroxisomal membrane proteins
(PMPs), termed the class I pathway, can be reconstituted in vitro by incubating
cell-free synthesized PMPs with highly purified peroxisomes at 26 degrees C for
1 h. This method ensures that the proteins targeted to peroxisomes are imported
directly without involvement of other organelles.
PMID- 28409465
TI - Peroxisomal Membrane and Matrix Protein Import Using a Semi-Intact Mammalian Cell
System.
AB - Peroxisomes are essential intracellular organelles that catalyze a number of
essential metabolic pathways including beta-oxidation of very long chain fatty
acids, synthesis of plasmalogen, bile acids, and generation and degradation of
hydrogen peroxide. These peroxisomal functions are accomplished by strictly and
spatiotemporally regulated compartmentalization of the enzymes catalyzing these
reactions. Defects in peroxisomal protein import result in inherited peroxisome
biogenesis disorders in humans. Peroxisomal matrix and membrane proteins are
synthesized on free ribosomes and transported to peroxisomes in a manner
dependent on their specific targeting signals and their receptors. Peroxisomal
protein import can be analyzed using a semi-intact assay system, in which
targeting efficiency is readily monitored by immunofluorescence microscopy.
Furthermore, cytosolic factors required for peroxisomal protein import can be
manipulated, suggesting that the semi-intact system is a useful and convenient
system to uncover the molecular mechanisms of peroxisomal protein import.
PMID- 28409466
TI - The Use of Glycosylation Tags as Reporters for Protein Entry into the Endoplasmic
Reticulum in Yeast and Mammalian Cells.
AB - N-glycosylation is a process occurring in the Endoplasmic Reticulum (ER) in
nearly every organism. Proteins containing a glycosylation site are quickly
glycosylated by oligosaccharyltransferases once the glycosylation site is exposed
to the ER lumen. The oligosaccharide tree is then modified and proteins are
targeted to specific organelles or subcompartments. For a long time peroxisomal
membrane proteins (PMP) were thought to be targeted directly to the peroxisome.
However, in the course of recent years, several PMPs were found to be targeted
via the ER. Glycosylation increases the molecular weight of a protein, which is
easily detected by Western blotting. Glycosylation tags like the opsin tag are
therefore useful tools in the study of ER entry of peroxisomal proteins.
PMID- 28409467
TI - Detection of Ubiquitinated Peroxisomal Proteins in Yeast.
AB - Ubiquitination is involved in different aspects of peroxisome formation,
maintenance, and degradation. Consequently, simple methods for detecting
ubiquitinated peroxisomal proteins are extremely useful in peroxisomal research.
Here, we describe an immunoprecipitation-based technique that can be used to
assess peroxisomal protein ubiquitination in yeast.
PMID- 28409468
TI - Assessing Pexophagy in Mammalian Cells.
AB - In mammalian cells several hundred peroxisomes are maintained by a balance
between the biogenesis and turnover by peroxisome homeostasis. Pexophagy, a form
of autophagy specific for peroxisomes, is the main pathway for peroxisome
degradation, but molecular mechanisms of mammalian pexophagy are largely unknown.
This is due to the lack of well-established pexophagy-inducing conditions in
mammalian cells. Recently, several conditions that induce pexophagy were
described for mammalian cells, involving ubiquitin and adaptor proteins of
autophagy. In this chapter, we describe the protocol for Pex3-induced pexophagy,
the more readable and highly inducible pexophagy condition in mammalian cells.
PMID- 28409469
TI - Experimental Systems to Study Yeast Pexophagy.
AB - Peroxisome abundance is tightly regulated according to the physiological
contexts, through regulations of both proliferation and degradation of the
organelles. Here, we describe detailed methods to analyze processes for
autophagic degradation of peroxisomes, termed pexophagy, in yeast organisms. The
assay systems include a method for biochemical detection of pexophagy completion,
and one for microscopic visualization of specialized membrane structures acting
in pexophagy. As a model yeast organism utilized in studies of pexophagy, the
methylotrophic yeast Komagataella phaffii (Pichia pastoris) is referred to in
this chapter and related information on the studies with baker's yeast
(Saccharomyces cerevisiae) is also included. The described techniques facilitate
elucidation of molecular machineries for pexophagy and understanding of
peroxisome-selective autophagic pathways.
PMID- 28409470
TI - Flow Cytometric Analysis of the Expression Pattern of Peroxisomal Proteins,
Abcd1, Abcd2, and Abcd3 in BV-2 Murine Microglial Cells.
AB - Microglial cells play important roles in neurodegenerative diseases including
peroxisomal leukodystrophies. The BV-2 murine immortalized cells are widely used
in the context of neurodegenerative researches. It is therefore important to
establish the expression pattern of peroxisomal proteins by flow cytometry in
these cells. So, the expression pattern of various peroxisomal transporters
(Abcd1, Abcd2, Abcd3) contributing to peroxisomal beta-oxidation was evaluated on
BV-2 cells by flow cytometry and complementary methods (fluorescence microscopy,
and RT-qPCR). By flow cytometry a strong expression of peroxisomal proteins
(Abcd1, Abcd2, Abcd3) was observed. These data were in agreement with those
obtained by fluorescence microscopy (presence of numerous fluorescent dots in the
cytoplasm characteristic of a peroxisomal staining pattern) and RT-qPCR (high
levels of Abcd1, Abcd2, and Abcd3 mRNAs). Thus, the peroxisomal proteins (Abcd1,
Abcd2, Abcd3) are expressed in BV-2 cells, and can be analyzed by flow cytometry.
PMID- 28409471
TI - Study of Peroxisomal Protein Phosphorylation by Functional Proteomics.
AB - Reversible protein phosphorylation is a frequently occurring posttranslational
modification mediated by protein kinases and phosphatases that plays an essential
role in the regulation of a large number of cellular processes. Evidence is
accumulating that protein phosphorylation is also an important mechanism
governing processes associated with peroxisome biology. For an improved and
detailed understanding of these processes and their regulation it is therefore
crucial to study phosphorylation of peroxisome-associated proteins and to
determine the phosphorylated amino acid(s). To place peroxisome-related processes
into a larger, cellular context, it is further required to identify the kinases
and phosphatases catalyzing phosphorylation and dephosphorylation events in
peroxisomal proteins. We here provide a strategy for the targeted analysis of
peroxisomal phosphoproteins of Saccharomyces cerevisiae combining affinity
purification of epitope-tagged peroxisomal proteins with Phos-tag SDS-PAGE and
high-resolution mass spectrometry (MS) for the identification and precise
localization of in vivo phosphosites. Furthermore, we describe a protocol for an
MS-based in vitro kinase assay using recombinant peroxisomal proteins and a
selected kinase facilitating the site-resolved analysis of kinase-substrate
relationships.
PMID- 28409472
TI - Analysis of Peroxisomal beta-Oxidation During Storage Oil Mobilization in
Arabidopsis thaliana Seedlings.
AB - Peroxisomal beta-oxidation in plants is essential for mobilization of storage oil
in seed-oil storing plants, such as Arabidopsis thaliana. In plants, degradation
of fatty acids occurs exclusively in peroxisomes via beta-oxidation, driving
seedling growth and development upon germination. Thus, the determination of
storage oil breakdown rates is a useful approach to investigate defects in
peroxisomal beta-oxidation. Here we describe an acid catalyzed derivatization
process of fatty acids representing a fast and efficient procedure to generate
high yields of fatty acid methyl esters (FAMEs). The subsequent analysis by gas
chromatography coupled to mass spectrometry (GC-MS) allows the quantification of
total fatty acid content. The results provide detailed information of the
complete storage oil breakdown process via peroxisomal beta-oxidation during
seedling growth.
PMID- 28409473
TI - Peroxisome Mini-Libraries: Systematic Approaches to Study Peroxisomes Made Easy.
AB - High-throughput methodologies have been extensively used in the budding yeast,
Saccharomyces cerevisiae, to uncover fundamental principles of cell biology. Over
the years, several collections of yeast strains (libraries) were built to enable
systematic exploration of cellular functions. However, using these libraries
experimentally is often labor intensive and restricted to laboratories that hold
high throughput platforms. Utilizing the available full genome libraries we
handpicked a subset of strains that represent all known and predicted peroxisomal
proteins as well as proteins that have central roles in peroxisome biology. These
smaller collections of strains, mini-libraries, can be rapidly and easily used
for complicated screens by any lab. Since one of the libraries is built such that
it can be easily modified in the tag, promoter and selection, we also discuss how
these collections form the basis for creating a diversity of new peroxisomal
libraries for future studies. Using manual tools, available in any yeast lab,
coupled with few simple genetic approaches, we will show how these libraries can
be "mixed and matched" to create tailor made libraries for screening. These yeast
collections may now be exploited to study uncharted territories in the biology of
peroxisomes by anyone, anywhere.
PMID- 28409474
TI - Generation of Peroxisome-Deficient Somatic Animal Cell Mutants.
AB - Cell mutants with a genetic defect affecting various cellular phenotypes are
widely utilized as a powerful tool in genetic, biochemical, and cell biological
research. More than a dozen complementation groups of animal somatic mutant cells
defective in peroxisome biogenesis have been successfully isolated in Chinese
hamster ovary (CHO) cells and used as a model system reflecting fatal human
severe genetic disorders named peroxisome biogenesis disorders (PBD). Isolation
and characterization of peroxisome-deficient CHO cell mutants has allowed the
identification of PEX genes and the gene products peroxins, which directly leads
to the accomplishment of isolation of pathogenic genes responsible for human
PBDs, as well as elucidation of their functional roles in peroxisome biogenesis.
Here, we describe the procedure to isolate peroxisome-deficient mammalian cell
mutants from CHO cells, by making use of an effective, photo-sensitized selection
method.
PMID- 28409475
TI - Clinical and Laboratory Diagnosis of Peroxisomal Disorders.
AB - The peroxisomal disorders (PDs) are a heterogeneous group of genetic diseases in
man caused by an impairment in peroxisome biogenesis or one of the metabolic
functions of peroxisomes. Thanks to the revolutionary technical developments in
gene sequencing methods and their increased use in patient diagnosis, the field
of genetic diseases in general and peroxisomal disorders in particular has
dramatically changed in the last few years. Indeed, several novel peroxisomal
disorders have been identified recently and in addition it has been realized that
the phenotypic spectrum of patients affected by a PD keeps widening, which makes
clinical recognition of peroxisomal patients increasingly difficult. Here, we
describe these new developments and provide guidelines for the clinical and
laboratory diagnosis of peroxisomal patients.
PMID- 28409476
TI - The effects of hyperoxia on microvascular endothelial cell proliferation and
production of vaso-active substances.
AB - BACKGROUND: Hyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13%
O2, frequently occurs in hospitalized patients due to administration of
supplemental oxygen. Increasing evidence suggests that hyperoxia induces
vasoconstriction in the systemic (micro)circulation, potentially affecting organ
perfusion. This study addresses effects of hyperoxia on viability, proliferative
capacity, and on pathways affecting vascular tone in cultured human microvascular
endothelial cells (hMVEC). METHODS: hMVEC of the systemic circulation were
exposed to graded oxygen fractions of 20, 30, 50, and 95% O2 for 8, 24, and 72 h.
These fractions correspond to 152, 228, 380, and 722 mmHg, respectively. Cell
proliferation and viability was measured via a proliferation assay, peroxynitrite
formation via anti-nitrotyrosine levels, endothelial nitric oxide synthase
(eNOS), and endothelin-1 (ET-1) levels via q-PCR and western blot analysis.
RESULTS: Exposing hMVEC to 50 and 95% O2 for more than 24 h impaired cell
viability and proliferation. Hyperoxia did not significantly affect nitrotyrosine
levels, nor eNOS mRNA and protein levels, regardless of the exposure time or
oxygen concentration used. Phosphorylation of eNOS at the serine 1177 (S1177)
residue and ET-1 mRNA levels were also not significantly affected. CONCLUSIONS:
Exposure of isolated human microvascular endothelial cells to marked hyperoxia
for more than 24 h decreases cell viability and proliferation. Our results do not
support a role of eNOS mRNA and protein or ET-1 mRNA in the potential
vasoconstrictive effects of hyperoxia on isolated hMVEC.
PMID- 28409478
TI - Reversing Racial Inequities at the End of Life: A Call for Health Systems to
Create Culturally Competent Advance Care Planning Programs Within African
American Communities.
AB - Racial and cultural barriers inherent in health systems have made the delivery of
culturally relevant end of life care that aligns with patient preferences a
particular challenge across African American patient populations. The end of life
experience has been cited as a public health crisis by the Institute of Medicine
(IOM), and this crisis is one felt even more acutely by patients of this minority
race. Structural racism has limited access to the planning mechanisms proven to
result in quality end of life care; thus, health systems must initiate remedies
in the face of dire need, as African Americans face a disproportionate burden of
morbidity and mortality from many serious illnesses. Recognizing that education
is essential to overcoming barriers to quality care access, the development of
new and culturally appropriate models of community engagement surrounding advance
care planning is needed to serve and empower African American patients.
PMID- 28409477
TI - Ethnic Differences in Persistence with COPD Medications: a Register-Based Study.
AB - BACKGROUND: Long-acting bronchodilators (LABDs) are recommended as a first-line
maintenance therapy in patients with moderate or severe chronic obstructive
pulmonary disease (COPD). The aim of the study was to explore potential ethnic
differences in persistence with LABD in COPD patients. METHODS: A cohort of COPD
patients diagnosed in 2003-2007 in Copenhagen, Denmark, was followed for 2 years
in the Danish national registers. According to the number of the LABD medications
dispensed, individuals were categorized into three therapy groups: monotherapy,
drug combination therapy, and multiple drug therapy. Persistence was defined as
the period from the first prescription date to the date of discontinuation.
Treatment was considered discontinued if the interval between the two
prescriptions was longer than the number of days of cumulative medication supply
according to defined daily doses plus 7 days. RESULTS: In total, 1129 incident
COPD patients using LABDs were included; 6.7% had other than Danish ethnic
background. Survival analyses showed that in the cases where LABD medication
combination presented COPD maintenance therapy, ethnic background was associated
with the higher risk of the therapy discontinuation: HR = 1.40, 95% CI = 1.03
1.90, p = 0.03. There were no ethnic differences in persistence in the
monotherapy or multiple therapy groups. CONCLUSIONS: COPD patients with other
than Danish ethnic background discontinued COPD maintenance therapy more often
than ethnic Danes. Attention to the barriers of persistent COPD medication use in
COPD patients from ethnic minorities should be payed to facilitate better COPD
management.
PMID- 28409479
TI - Erratum.
PMID- 28409480
TI - Genetic Testing for Opioid Pain Management: A Primer.
AB - Patients see their primary care physicians (PCPs) for a variety of medical
conditions, chronic pain being one of the most common. An increased use of
prescription medications (especially opioids) has led to an increase in adverse
drug reactions and has heightened our awareness of the variability in response to
medications. Opioids and other pain adjuvants are widely used, and drug-drug
interactions involving these analgesics can be problematic and potentially
lethal. Pharmacogenetics has improved our understanding of drug efficacy and
response, opened doors to individual tailoring of medical management, and created
a series of ethical and economic considerations. Since it is a relatively new
field, genetic testing has not been fully integrated into the primary care
setting. The purpose of this paper is to review the metabolism of commonly
prescribed opioids, discuss the economic and ethical issues, and provide PCPs
with an understanding of how to incorporate genetic testing into routine use to
improve clinical practice and patient management.
PMID- 28409481
TI - Views of the UK General Public on Important Aspects of Health Not Captured by EQ
5D.
AB - INTRODUCTION: The EQ-5D is a standardised instrument designed for use as a
generic measure of health outcome. It was (and is) intended to provide
information about a 'common core' of dimensions known to be relevant across a
range of conditions; however, the five dimensions may not fully capture the
health-related impacts of certain conditions. This study analyses the views of
the UK general public about important aspects of health considered to be missing
from the instrument. METHODS: Survey respondents were asked whether there are any
aspects of health they consider to be important but are not captured by the EQ
5D, and, if so, what these aspects are. The responses (text comments) were
analysed using content analysis with analyst triangulation. Data were collected
from a broadly representative sample of the general public via a paper
questionnaire administered as part of face-to-face interviews. RESULTS: Data are
available for 436 respondents, 179 of whom suggested aspects of health they
considered important but not captured by the five EQ-5D dimensions. These were
organised into 22 themes. Sensory deprivation and mental health were the health
aspects most commonly mentioned by respondents. CONCLUSIONS: Respondents
identified several important aspects of health that are not covered by the EQ-5D
descriptive system. This study can provide the basis for more detailed
qualitative and quantitative research-in particular to examine the views of
different patient groups-to inform further review of the EQ-5D descriptive
system. The results also have implications for the sensitivity of other generic
measures.
PMID- 28409483
TI - Erratum to: Modeling stimulus variation in three common implicit attitude tasks.
PMID- 28409484
TI - The state of web-based research: A survey and call for inclusion in curricula.
AB - The first papers that reported on conducting psychological research on the web
were presented at the Society for Computers in Psychology conference 20 years
ago, in 1996. Since that time, there has been an explosive increase in the number
of studies that use the web for data collection. As such, it seems a good time,
20 years on, to examine the health and adoption of sound practices of research on
the web. The number of studies conducted online has increased dramatically.
Overall, it seems that the web can be a method for conducting valid psychological
studies. However, it is less clear that students and researchers are aware of the
nature of web research. While many studies are well conducted, there is also a
certain laxness appearing regarding the design and conduct of online studies.
This laxness appears both anecdotally to the authors as managers of large sites
for posting links to online studies, and in a survey of current researchers. One
of the deficiencies discovered is that there is no coherent approach to educating
researchers as to the unique features of web research.
PMID- 28409482
TI - Efficacy of Interferon-Free Therapies for Chronic Hepatitis C: A Systematic
Review of All Randomized Clinical Trials.
AB - BACKGROUND AND OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have
recently arisen as more effective and safer treatments for chronic hepatitis C.
These drugs can be combined into treatments without interferon (IFN), and are
therefore called IFN-free therapies. OBJECTIVE: The objective of this study
systematic review was to evaluate the efficacy of IFN-free therapies for the
treatment of chronic hepatitis C, and thus increase the clinical evidence for
these therapies. METHODS: A systematic review was conducted in accordance with
Cochrane Collaboration recommendations. A search was performed in six different
electronic databases using 'clinical trials', 'hepatitis C' and 'interferon-free'
as the main descriptors, and studies that conformed to the inclusion criteria had
their data extracted, including study information, baseline characteristics, and
efficacy outcomes (sustained virologic response, rapid virologic response, and
virologic failure). RESULTS: Sixty-four randomized clinical trials including 15
different therapies were included in a total of 15,731 patients infected with the
hepatitis C virus, mostly with genotype 1, and mainly treated for 12 or 24 weeks.
The sustained virologic response rate after 12 weeks of treatment was
approximately 89%, while the virologic failure rate was below 5%. CONCLUSIONS:
Second-generation DAAs presented several advantages: virologic response values
higher than the average achieved by previous IFN-based therapies, reduced
treatment duration, and the possibility of different combinations of therapies to
meet patient needs. Thus, IFN-free therapies appear to be valuable alternatives
for the treatment of chronic hepatitis C.
PMID- 28409485
TI - Cohesion network analysis of CSCL participation.
AB - The broad use of computer-supported collaborative-learning (CSCL) environments
(e.g., instant messenger-chats, forums, blogs in online communities, and massive
open online courses) calls for automated tools to support tutors in the time
consuming process of analyzing collaborative conversations. In this article, the
authors propose and validate the cohesion network analysis (CNA) model, housed
within the ReaderBench platform. CNA, grounded in theories of cohesion,
dialogism, and polyphony, is similar to social network analysis (SNA), but it
also considers text content and discourse structure and, uniquely, uses automated
cohesion indices to generate the underlying discourse representation. Thus, CNA
enhances the power of SNA by explicitly considering semantic cohesion while
modeling interactions between participants. The primary purpose of this article
is to describe CNA analysis and to provide a proof of concept, by using ten chat
conversations in which multiple participants debated the advantages of CSCL
technologies. Each participant's contributions were human-scored on the basis of
their relevance in terms of covering the central concepts of the conversation.
SNA metrics, applied to the CNA sociogram, were then used to assess the quality
of each member's degree of participation. The results revealed that the CNA
indices were strongly correlated to the human evaluations of the conversations.
Furthermore, a stepwise regression analysis indicated that the CNA indices
collectively predicted 54% of the variance in the human ratings of participation.
The results provide promising support for the use of automated computational
assessments of collaborative participation and of individuals' degrees of active
involvement in CSCL environments.
PMID- 28409486
TI - Dutch taboo norms.
AB - This article provides norms for general taboo, personal taboo, insult, valence,
and arousal for 672 Dutch words, including 202 taboo words. Norms were collected
using a 7-point Likert scale and based on ratings by psychology students from the
Erasmus University Rotterdam in The Netherlands. The sample consisted of 87
psychology students (58 females, 29 males). We obtained high reliability based on
split-half analyses. Our norms show high correlations with arousal and valence
ratings collected by another Dutch word-norms study (Moors et al.,, Behavior
Research Methods, 45, 169-177, 2013). Our results show that the previously found
quadratic relation (i.e., U-shaped pattern) between valence and arousal also
holds when only taboo words are considered. Additionally, words rated high on
taboo tended to be rated low on valence, but some words related to sex rated high
on both taboo and valence. Words that rated high on taboo rated high on insult,
again with the exception of words related to sex many of which rated low on
insult. Finally, words rated high on taboo and insult rated high on arousal. The
Dutch Taboo Norms (DTN) database is a useful tool for researchers interested in
the effects of taboo words on cognitive processing. The data associated with this
paper can be accessed via the Open Science Framework ( https://osf.io/vk782/ ).
PMID- 28409487
TI - Scanpath modeling and classification with hidden Markov models.
AB - How people look at visual information reveals fundamental information about them;
their interests and their states of mind. Previous studies showed that scanpath,
i.e., the sequence of eye movements made by an observer exploring a visual
stimulus, can be used to infer observer-related (e.g., task at hand) and stimuli
related (e.g., image semantic category) information. However, eye movements are
complex signals and many of these studies rely on limited gaze descriptors and
bespoke datasets. Here, we provide a turnkey method for scanpath modeling and
classification. This method relies on variational hidden Markov models (HMMs) and
discriminant analysis (DA). HMMs encapsulate the dynamic and individualistic
dimensions of gaze behavior, allowing DA to capture systematic patterns
diagnostic of a given class of observers and/or stimuli. We test our approach on
two very different datasets. Firstly, we use fixations recorded while viewing 800
static natural scene images, and infer an observer-related characteristic: the
task at hand. We achieve an average of 55.9% correct classification rate (chance
= 33%). We show that correct classification rates positively correlate with the
number of salient regions present in the stimuli. Secondly, we use eye positions
recorded while viewing 15 conversational videos, and infer a stimulus-related
characteristic: the presence or absence of original soundtrack. We achieve an
average 81.2% correct classification rate (chance = 50%). HMMs allow to integrate
bottom-up, top-down, and oculomotor influences into a single model of gaze
behavior. This synergistic approach between behavior and machine learning will
open new avenues for simple quantification of gazing behavior. We release SMAC
with HMM, a Matlab toolbox freely available to the community under an open-source
license agreement.
PMID- 28409488
TI - A Joint Model for Vitamin K-Dependent Clotting Factors and Anticoagulation
Proteins.
AB - BACKGROUND: Warfarin acts by inhibiting the reduction of vitamin K (VK) to its
active form, thereby decreasing the production of VK-dependent coagulation
proteins. The aim of this research is to develop a joint model for the VK
dependent clotting factors II, VII, IX and X, and the anticoagulation proteins,
proteins C and S, during warfarin initiation. METHODS: Data from 18 patients with
atrial fibrillation who had warfarin therapy initiated were available for
analysis. Nine blood samples were collected from each subject at baseline, and at
1-5, 8, 15 and 29 days after warfarin initiation and assayed for factors II, VII,
IX and X, and proteins C and S. Warfarin concentration-time data were not
available. The coagulation proteins data were modelled in a stepwise manner using
NONMEM(r) Version 7.2. In the first stage, each of the coagulation proteins was
modelled independently using a kinetic-pharmacodynamic model. In the subsequent
step, the six kinetic-pharmacodynamic models were combined into a single joint
model. RESULTS: One patient was administered VK and was excluded from the
analysis. Each kinetic-pharmacodynamic model consisted of two parts: (1) a common
one-compartment pharmacokinetic model with first-order absorption and elimination
for warfarin; and (2) an inhibitory E max model linked to a turnover model for
coagulation proteins. In the joint model, an unexpected pharmacodynamic lag was
identified and the estimated degradation half-life of VK-dependent coagulation
proteins were in agreement with previously published values. The model provided
an adequate fit to the observed data. CONCLUSION: The joint model represents the
first work to quantify the influence of warfarin on all six VK-dependent
coagulation proteins simultaneously. Future work will expand the model to predict
the influence of exogenously administered VK on the time course of clotting
factor concentrations after warfarin overdose and during perioperative warfarin
reversal procedures.
PMID- 28409489
TI - Cost of Trauma Care in Secondary- and Tertiary-Care Public Sector Hospitals in
North India.
AB - BACKGROUND: Several initiatives to provide trauma care, including ambulance
services, creation of a network of trauma hospitals and insurance schemes for
cashless treatment, are currently being implemented in India. However, lack of
information on the cost of trauma care is an impediment to the evidence-based
planning for such initiatives. In this study, we aim to bridge this gap in
evidence by estimating the unit cost of an outpatient consultation, inpatient bed
day of hospitalization, surgical procedure and diagnostics for providing trauma
care through secondary- and tertiary-level hospitals in India. METHODS: We
undertook an economic costing of trauma care in a secondary-care district
hospital and a tertiary-level teaching and research hospital in North India. Cost
analysis was undertaken using a health system perspective, employing a bottom-up
costing methodology. Data on all resources-capital or recurrent-on delivery of
trauma care during the period of April 2014 to March 2015 were collected.
Standardized unit costs were estimated after adjusting for bed occupancy rates.
Sensitivity analysis was performed to account for the uncertainties due to
differences in prices and other assumptions. RESULTS: The cost of trauma care in
the tertiary care hospital was INR 9585 (US$147.4) per day-care consultation; INR
2470 (US$37.7) per bed-day hospitalization (excluding ICU), INR 12,905 (US$198.5)
per bed day in ICU and INR 21,499 (US$330.8) per surgery. Similarly, in the
secondary-care hospital, the cost of trauma care was INR 482 (US$7.4) per
outpatient consultation, INR 791 (US$12.2) per bed day of hospitalization, INR
186 (US$2.9) per minor surgery and INR 6505 (US$100.1) per major surgery.
CONCLUSION: The estimates generated can be used for planning and managing trauma
care services in India. The findings may also be used for undertaking future
research in estimating the cost effectiveness of trauma care services or models
of care.
PMID- 28409490
TI - Risk of Suicidality in People with Psoriasis: A Systematic Review and Meta
Analysis of Cohort Studies.
AB - BACKGROUND: Psoriasis has been associated with psychiatric disorders such as
depression and anxiety, but its relationship with suicidality (including suicide,
suicide attempt, and suicidal ideation) is unclear. OBJECTIVE: Our objective was
to assess the risk of suicide, suicide attempt, suicidal ideation, and
suicidality in people with psoriasis. METHODS: We conducted a systematic review
and meta-analysis of cohort studies examining the risk of suicide, suicide
attempt, suicidal ideation, and suicidality in people with psoriasis. We searched
the Cochrane Library, PubMed, and EMBASE from inception to 24 March 2017. Two
authors independently selected studies, assessed the quality of included studies,
and extracted data. Any disagreement was resolved by discussion with a third
author. RESULTS: Five population-based cohort studies were included and
considered to be of high quality. We found no increase in the risk of suicide
(risk ratio [RR] 1.13; 95% confidence interval [CI] 0.87-1.46), suicide attempt
(RR 1.25; 95% CI 0.89-1.75), or suicidality (RR 1.26; 95% CI 0.97-1.64) among
people with psoriasis. In the stratified analysis, we also found no increase in
suicide, suicide attempt, and suicidality among people with either severe or mild
psoriasis. CONCLUSIONS: The available limited, very low-quality evidence does not
support an association between psoriasis and suicidal thought and behavior.
Further studies that provide data for different age and sex groups are needed to
clarify whether a subgroup of patients with psoriasis has an elevated risk of
suicidality.
PMID- 28409491
TI - Obesity: Rubensian beauty turned into major health problem.
PMID- 28409492
TI - Resisting small cake phenomenon - sharing resources and knowledge makes you rich.
PMID- 28409494
TI - Association between metabolically healthy central obesity in women and levels of
soluble receptor for advanced glycation end products, soluble vascular adhesion
protein-1, and the activity of semicarbazide-sensitive amine oxidase.
AB - AIM: To determine the levels of circulating soluble receptor for advanced
glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and
cardiovascular disease development in centrally obese (CO) women considered
metabolically healthy (COH) in comparison with those metabolically unhealthy
(COU). METHODS: 47 lean healthy, 17 COH (presenting waist-to-height ratio >=0.5
but not elevated blood pressure, atherogenic lipid profile, and insulin
resistance), and 50 COU (CO presenting >=2 risk factors) women aged 40-45 years
were included. Anthropometric characteristics, blood chemistry and hematology
data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion
protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase
(SSAO) were determined. RESULTS: Central obesity associated with low sRAGE levels
(lean healthy: 1503+/-633 pg/mL; COH: 1103+/-339 pg/mL, P<0.05; COU: 1106+/-367
ng/mL, P<0.0.1), hyperleptinemia, and elevated markers of inflammation
irrespective of the presence or absence of cardiometabolic risk factors. COU
women presented high adiponectin levels. SVAP-1 concentrations and the activity
of SSAO were similar in all 3 groups. CONCLUSION: COH women present abnormalities
in non-standard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C
reactive protein), supporting the view that there is no healthy pattern of
obesity. The clinical impact of our findings for future prognosis of
metabolically healthy obese subjects remains to be elucidated in longitudinal
studies.
PMID- 28409493
TI - Obesity in pregnancy: a novel concept on the roles of adipokines in uterine
contractility.
AB - Obesity is a global health problem even among pregnant women. Obesity alters
quality of labor, such as preterm labor, prolonged labor, and higher oxytocin
requirements in pregnant women. The most important factors to play a role in the
altered gestational period and serve as drug targets to treat the consequences
are female sexual hormones, calcium channels, adrenergic system, oxytocin, and
prostaglandins. However, we have limited information about the impact of obesity
on the pregnant uterine contractility and gestation time. Adipose tissue, which
is the largest endocrine and paracrine organ, especially in obesity, is
responsible for the production of adipokines and various cytokines and
chemokines, and there are no reliable data available describing the relation
between body mass index, glucose intolerance, and adipokines during pregnancy.
Recent data suggest that the dysregulation of leptin, adiponectin, and kisspeptin
during pregnancy contributes to gestational diabetes mellitus and pre-eclampsia.
A preclinical method for obese pregnancy should be developed to clarify the
action of adipokines and assess their impact in obesity. The deeper understanding
of the adipokines-induced processes in obese pregnancy may be a step closer to
the prevention and therapy of preterm delivery or prolonged pregnancy.
Gestational weight gain is one of the factors that could influence the prenatal
development, birth weight, and adiposity of newborn.
PMID- 28409495
TI - Antiplatelet and anti-proliferative action of disintegrin from Echis
multisquamatis snake venom.
AB - AIM: To purify the platelet aggregation inhibitor from Echis multisquamatis snake
venom (PAIEM) and characterize its effect on platelet aggregation and HeLa cell
proliferation. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
(SDS-PAGE) and matrix assisted laser desorption/ionization time-of-flight (MALDI
TOF) were used for PAIEM identification. Platelet aggregation in the presence of
PAIEM was studied on aggregometer Solar-AP2110. The changes of shape and
granularity of platelets in the presence of PAIEM were studied on flow cytometer
COULTER EPICS XL, and degranulation of platelets was estimated using
spectrofluorimetry. Indirect enzyme-linked immunosorbent assay was used for the
determination of target of PAIEM on platelet surface. An assay based on 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to evaluate the
effect of PAIEM on the proliferation of HeLa cells in cell culture. RESULTS: The
molecular weight of the protein purified from Echis multisquamatis venom was 14.9
kDa. Half-maximal inhibitory concentration (IC50) of PAIEM needed to inhibit
adenosine diphosphate (ADP)-induced platelet aggregation was 7 MUM. PAIEM did not
affect thrombin- or ADP-induced platelet activation, but it did prevent binding
of the anti-IIb antibody to glycoprotein IIb/IIIa (GPIIbIIIa)-receptor of adhered
platelets and inhibited the viability of HeLa cells by 54%. CONCLUSION: As a
member of the disintegrin family, PAIEM inhibited platelet aggregation and cell
proliferation possibly by blocking integrin-mediated interactions. However, it
did not impair cellular signaling causing any changes in platelet shape and
granularity and did not affect ADP-induced platelet degranulation. This
disintegrin was shown to be a potent inhibitor of integrin-mediated cellular
interactions including platelet aggregation or cancer cell proliferation.
PMID- 28409496
TI - 4-Thiazolidinone derivative Les-3833 effectively inhibits viability of human
melanoma cells through activating apoptotic mechanisms.
AB - AIM: To evaluate cytotoxic action of 4-thiazolidinone derivative Les-3833 and
study the mechanisms of its pro-apoptotic action toward human melanoma cells and
human tumor cell lines of other tissue origin. METHODS: The effect of Les-3833 or
doxorubicin on the viability of 9 cell lines was studied using MTT assay, while
human melanoma cells of WM793 line were additionally examined using light and
fluorescent microscopies for evaluating cytomorphological changes. The Western
blot and flow cytometric analyses were carried out to study signaling pathways of
melanoma cell cycling and death. RESULTS: Les-3833 was the most efficient against
melanoma cells. Its half maximal inhibitory concentration (IC50) was 0.22 MUg/mL
for WM793 cells and 0.3 MUg/mL for SK-Mel-28 melanoma cells. For human lung A549,
breast MCF-7, colon HCT116, and ovarian SKOV3 carcinoma cell lines IC50 was in
between 2.5 to >5.0 MUg/mL. Les-3833 was relatively not toxic (IC50 > 5 MUg/mL)
for human embryonic kidney HEK293 cells. Results of Annexin V/PI staining of
melanoma cells and activation of caspase 3, PARP, MAPK, and EndoG protein suggest
apoptosis in Les-3833-treated cells. Les-3833 also induced ROS production in
melanoma cells and their arrest in G0/G1 phase of cell cycle. CONCLUSION: Novel 4
thiazolidinone derivative Les-3833 is effective against human melanoma cells in
vitro, and such effect is tumor specific since it is much less pronounced in
human carcinoma and leukemia cells. In melanoma cells Les-3833 induces apoptosis
(morphological changes and increased pro-apoptotic proteins), ROS production, and
arrest in G0/G1 phase of cell cycle.
PMID- 28409497
TI - Identification of myoelectric signals of pregnant rat uterus: new method to
detect myometrial contraction.
AB - AIM: To develop an electromyography method for pregnant rat uterus in vivo and to
separate myometrial signals from the gastrointestinal tract signals. METHODS:
Pregnant Sprague-Dawley rats (n=8) were anaesthetized and their stomach, small
intestine, and large intestine were removed from the abdomen. A pair of thread
electrodes was inserted into the uterus, while a pair of disk electrodes was
placed subcutaneously above the myometrium. Additionally, a strain gauge sensor
was fixed on the surface of the myometrium and cecum for the parallel detection
of mechanical contractions in rats (n=18) with intact gastrointestinal tract. The
filtered electric signals were amplified and recorded by an online computer
system and analyzed by fast Fourier transformation. The frequency of the electric
activity was characterized by cycle per minute (cpm), the magnitude of the
activity was described as power spectrum density maximum (PsDmax). RESULTS: The
frequency of the pregnant uterine activity was 1-3 cpm, which falls within the
same range as that of cecum. Measuring by both electrodes, oxytocin (1 ug/kg)
increased and terbutaline (50 ug/kg) decreased the PsDmax by 25%-50% (P<0.001)
and 25%-40% (P<0.01), respectively. We found a strong positive correlation
between the alterations of PsDmax values and the strain gauge sensor-detected
mechanical contractions (area under curve). The GI specific compounds
(neostigmine, atropine) mainly affected the cecal activity, while myometrium
specific drugs (oxytocin, terbutaline) influenced the myometrial signals only.
Conclusion Our method proved to be able to detect the myoelectric activity that
reflects the mechanical contraction. The overlapping myometrial and cecal signals
are not separable, but they can be distinguished based on the much higher
activity and different pharmacological reactivity of the pregnant uterus. Thus,
the early signs of contractions can be detected and labor may be predicted in a
fast and sensitive way.
PMID- 28409498
TI - Differential pro-apoptotic effects of synthetic 4-thiazolidinone derivative Les
3288, doxorubicin and temozolomide in human glioma U251 cells.
AB - AIM: To compare various pro-apoptotic effects of synthetic 4-thiazolidinone
derivative (Les-3288), doxorubicin (Dox) and temozolomide (TMZ) in the treatment
of human glioma U251 cells to improve treatment outcomes of glioblastoma and
avoid anticancer drug resistance. METHODS: The cytotoxic effects of drugs used in
human glioma U251 cells were measured by cell viability and proliferation assay
(MTT), Trypan blue exclusion test, and Western-blot analysis of the apoptosis
related proteins. In addition, flow cytometry study of reactive oxygen species
(ROS) level in glioma cells was carried out. Cytomorphological changes in treated
cells were monitored by fluorescent microscopy after cell staining with Hoechst
33342 and ethydium bromide. RESULTS: Half-maximal inhibitory concentration (IC50)
of Les-3288, Dox, and TMZ was calculated for human glioblastoma U251 cells. The
rating of the values of this indicator of cellular vitality was assessed. The
results of MTT assay proved the superiority of Les-3288 vs Les-3288>Dox>TMZ,
which is in agreement with the results of Trypan blue testing showing Les
3288~Dox>TMZ. In general, such ranking corresponded to a scale of pro-apoptotic
impairments in the morphology of glioma U251 cells and the results of Western
blot analysis of cleaved Caspase 3. Contrary to Dox, Les-3288 and TMZ did not
affect significantly ROS levels in the treated cells. CONCLUSION: The effect of
the synthetic 4-thiazolidinone derivative Les-3288 is realized via apoptosis
mechanisms and does not involve ROS. In comparison with Dox and TMZ, it is more
effective in destroying human glioblastoma U251 cells. Les-3288 compound has a
potential as an anticancer drug for glioblastoma. Nevertheless, further
preclinical studies of the blood-brain barrier are needed.
PMID- 28409499
TI - Use of placental vascularization indices and uterine artery peak systolic
velocity in early detection of pregnancies complicated by gestational diabetes,
chronic or gestational hypertension, and preeclampsia at risk.
AB - AIM: We aimed to investigate correlations between uterine artery peak systolic
velocity (AUtPSV), and placental vascularization in groups of normal blood
pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension
(CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in
combination with gestational diabetes mellitus (GDM), and hypothesized that
AUtPSV rises when GDM complicates pregnancy hypertension. METHODS: Placental 3
dimensional power Doppler indices, such as vascularization index (VI), flow index
(FI), and vascularization-flow index (VFI), and uterine artery peak systolic
velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57),
GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109).
Correlations were analyzed between vascularization indices, AUtPSV,
pregestational BMI and adverse pregnancy outcome rates. RESULTS: In our results
VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE
(P=0.001) compared to NBP. In case of VFI, significant difference was found
between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic
for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly
higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As
for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP
and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT
and GHT+GDM (P=0.048) groups. CONCLUSION: Our study revealed that vascularization
indices and AUtPSV show significant differences due to gestational pathology, and
can be useful in detection of pregnancies at risk.
PMID- 28409500
TI - Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma
bearing mice under doxorubicin treatment is not connected with their ROS
scavenging potential.
AB - AIM: To evaluate molecular mechanisms of tissue-protective effects of
antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in
combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. METHODS: Impact
of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro
and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma
cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity
of the drugs was evaluated by measuring creatinine indicator assay,
hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and
myelotoxicity was assessed by light microscopic analysis of blood smears. Changes
in ROS content in B16 melanoma cells under Dx, SeMet, and D-Pt action in vitro
were measured by incubation with fluorescent dyes
dihydrodichlorofluoresceindiacetate (DCFDA, H2O2-specific) and dihydroethidium
(DHE, O2--specific), and further analysis at FL1 (DCFDA) or FL2 channels (DHE) of
FACScan flow cytometer. The impact of aforementioned compounds on functional
status of mitochondria was measured by Rhodamine 123 assay and further analysis
at FL1 channel of FACScan flow cytometer. RESULTS: Selenomethionine (1200 ug/kg)
and D-pantethine (500 mg/kg) in combination with Dx (10 mg/kg) significantly
reduced tumor-induced neutrophilia, lymphocytopenia, and leukocytosis in
comparison to Dx treatment alone. Moreover, SeMet and D-Pt decreased several side
effects of Dx, namely an elevated creatinine level in blood and monocytosis, thus
normalizing health conditions of B16 melanoma-bearing animals. CONCLUSIONS: Our
results showed that antioxidants selenomethionine and D-pantethine possess
significant nephroprotective and myeloprotective activity toward Dx action on
murine B16 melanoma in vivo, but fail to boost a survival of B16 melanoma-bearing
animals. The observed cytoprotective effects of studied antioxidants are not
directly connected with their ROS scavenging.
PMID- 28409501
TI - Successful treatment of fulminant Lyme myocarditis with mechanical circulatory
support in a young male adult: a case report.
AB - We describe the case of fulminant myocarditis due to Lyme disease and use of
mechanical circulatory support (MCS) for the treatment of the Lyme carditis
associated with refractory cardiogenic shock. Fulminant Lyme myocarditis in young
adult male patient led to a sudden onset of acute, severe biventricular heart
failure with progressive cardiogenic shock, and multiorgan failure immediately
after admission.
PMID- 28409503
TI - Food restriction affects maternal investment but not neonate phenotypes in a
viviparous lizard.
AB - Food availability significantly affects an animal's energy metabolism, and thus
its phenotype, survival, and reproduction. Maternal and offspring responses to
food conditions are critical for understanding population dynamics and life
history evolution of a species. In this study, we conducted food manipulation
experiments in field enclosures to identify the effect of food restriction on
female reproductive traits and postpartum body condition, as well as on hatchling
phenotypes, in a lacertid viviparous lizard from the Inner Mongolian desert
steppe of China. Females under low-food availability treatment (LFT) had poorer
immune function and body condition compared with those under high-food
availability treatment (HFT). The food availability treatments significantly
affected the litter size and litter mass of the females, but not their gestation
period in captivity or brood success, or the body size, sprint speed, and sex
ratio of the neonates. Females from the LFT group had smaller litter sizes and,
therefore, lower litter mass than those from the HFT group. These results suggest
that female racerunners facing food restriction lay fewer offspring with
unchanged body size and locomotor performance, and incur a cost in the form of
poor postpartum body condition and immune function. The flexibility of maternal
responses to variable food availability represents an important life strategy
that could enhance the resistance of lizards to unpredictable environmental
change.
PMID- 28409504
TI - Comparative study of the transfection efficiency of commonly used viral vectors
in rhesus monkey (Macaca mulatta) brains.
AB - Viral vector transfection systems are among the simplest of biological agents
with the ability to transfer genes into the central nervous system. In brain
research, a series of powerful and novel gene editing technologies are based on
these systems. Although many viral vectors are used in rodents, their full
application has been limited in non-human primates. To identify viral vectors
that can stably and effectively express exogenous genes within non-human
primates, eleven commonly used recombinant adeno-associated viral and lentiviral
vectors, each carrying a gene to express green or red fluorescence, were injected
into the parietal cortex of four rhesus monkeys. The expression of fluorescent
cells was used to quantify transfection efficiency. Histological results revealed
that recombinant adeno-associated viral vectors, especially the serotype 2/9
coupled with the cytomegalovirus, human synapsin I, or Ca2+/calmodulin-dependent
protein kinase II promoters, and lentiviral vector coupled with the human
ubiquitin C promoter, induced higher expression of fluorescent cells,
representing high transfection efficiency. This is the first comparison of
transfection efficiencies of different viral vectors carrying different promoters
and serotypes in non-human primates (NHPs). These results can be used as an aid
to select optimal vectors to transfer exogenous genes into the central nervous
system of non-human primates.
PMID- 28409505
TI - Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri
chinensis) brain during postnatal development and aging.
AB - Brain development and aging are associated with alterations in multiple
epigenetic systems, including DNA methylation and demethylation patterns. Here,
we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven
translocation (TET) enzyme-mediated active DNA demethylation products were
dynamically changed and involved in postnatal brain development and aging in tree
shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic
structures showed a gradual increase throughout postnatal development, whereas a
significant decrease in 5hmC was found in several brain regions in aged tree
shrews, including in the prefrontal cortex and hippocampus, but not the
cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3
predominantly contributed to the changes in 5hmC levels. Our findings provide new
insight into the dynamic changes in 5hmC levels in tree shrew brains during
postnatal development and aging processes.
PMID- 28409506
TI - Characterization of cyclophilin D in freshwater pearl mussel (Hyriopsis
schlegelii).
AB - Cyclophilin D (referred to as HsCypD) was obtained from the freshwater pearl
mussel (Hyriopsis schlegelii). The full-length cDNA was 2 671 bp, encoding a
protein consisting of 367 amino acids. HsCypD was determined to be a hydrophilic
intracellular protein with 10 phosphorylation sites and four tetratricopeptide
repeat (TPR) domains, but no signal peptide. The core sequence region
YKGCIFHRIIKDFMVQGG is highly conserved in vertebrates and invertebrates.
Phylogenetic tree analysis indicated that CypD from all species had a common
origin, and HsCypD had the closest phylogenetic relationship with CypD from
Lottia gigantea. The constitutive mRNA expression levels of HsCypD exhibited
tissue-specific patterns, with the highest level detected in the intestines,
followed by the gonads, and the lowest expression found in the hemocytes.
PMID- 28409507
TI - FasParser: a package for manipulating sequence data.
AB - A computer software package called 'FasParser' was developed for manipulating
sequence data. It can be used on personal computers to perform series of
analyses, including counting and viewing differences between two sequences at
both DNA and codon levels, identifying overlapping regions between two
alignments, sorting of sequences according to their IDs or lengths, concatenating
sequences of multiple loci for a particular set of samples, translating
nucleotide sequences to amino acids, and constructing alignments in several
different formats, as well as some extracting and filtrating of data for a
particular FASTA file. Majority of these functions can be run in a batch mode,
which is very useful for analyzing large data sets. This package can be used by a
broad audience, and is designed for researchers that do not have programming
experience in sequence analyses. The GUI version of FasParser can be downloaded
from https://github.com/Sun-Yanbo/FasParser, free of charge.
PMID- 28409508
TI - Performance of muscle strength and fatigue tolerance in young trained women
supplemented with caffeine.
AB - BACKGROUND: The aim of this paper was to verify the effect of caffeine
supplementation on the muscular strength and fatigue tolerance of young trained
women. METHODS: Eight women of 25+/-5-years-old, who had undergone a minimum of
12 months of continuous resisted training, Body Mass Index 20-23 kg/m2 were
submitted to 4 tests: One Repetition Maximum (1-RM, kg) to pull down (PD), Hack
Squat (HS), Bench Press (BP), and Knee Extension Exhaustion (drop-set, 100/80/60
kg, repetitions) (DS). They performed the tests in 4 consecutive blocks one-week
apart crossover system: basal without caffeine (B); first caffeine (C1); placebo
with starch supplementation (P); second caffeine (C2). Caffeine supplementation 6
mg.kg-1 30 minutes before. The paired t-test and repeated ANOVA with Tukey-Kramer
were performed. RESULTS: Respectively for B, C1, P and C2 to each test were PD
(52, 54, 56, 55, P>0.05); HS (99, 109, 108, 121*; P<0.001); BP (22, 26*, 25*,
27*; P<0.05); DS (28, 35*,**, 30*, 37**; P<0.001). To comparison of B, P and mean
caffeine (C1+C2/2) results respectively were: HS (99, 108*, 115***; P<0.05); BP
(22, 25*, 26*; P<0.05); DS (28, 30#, 36**; P<0.01 and P<0.001). The delta
([C1+C2/2]-[B+P/2]) were PD=0 (P>0.05), HS=12 (P=0.04), BP=3 (P=0.007), DS=7
(P=00.1). CONCLUSIONS: Caffeine improved tolerance to exhaustion and has tendency
to improve strength in this young women. Probably caffeine supplementation is
useful to improve performance in women engaged in sports with these physical
valences. An investigation with a major numbers of volunteers could elucidate
some controversies observed here.
PMID- 28409509
TI - Fitness as a determinant of arterial stiffness in healthy adult men: a cross
sectional study.
AB - BACKGROUND: Fitness is known to influence arterial stiffness. This study aimed to
assess differences in cardiorespiratory endurance, muscular strength, and
flexibility according to arterial stiffness, based on sex and age. METHODS: We
enrolled 1590 healthy adults (men: 1242, women: 348) who were free of metabolic
syndrome. We measured cardiorespiratory endurance in an exercise stress test on a
treadmill, muscular strength by a grip test, and flexibility by upper body
forward-bends from a standing position. The brachial-ankle pulse wave velocity
test was performed to measure arterial stiffness before the fitness test. Cluster
analysis was performed to divide the patients into groups with low (Cluster 1)
and high (Cluster 2) arterial stiffness. According to the k-cluster analysis
results, Cluster 1 included 624 men and 180 women, and Cluster 2 included 618 men
and 168 women. RESULTS: Men in the middle-aged group with low arterial stiffness
demonstrated higher cardiorespiratory endurance, muscular strength, and
flexibility than those with high arterial stiffness. Similarly, among men in the
old-aged group, the cardiorespiratory endurance and muscular strength, but not
flexibility, differed significantly according to arterial stiffness. Women in
both clusters showed similar cardiorespiratory endurance, muscular strength, and
flexibility regardless of their arterial stiffness. CONCLUSIONS: Among healthy
adults, arterial stiffness was inversely associated with fitness in men but not
in women. Therefore, fitness seems to be a determinant for arterial stiffness in
men. Additionally, regular exercise should be recommended for middle-aged men to
prevent arterial stiffness.
PMID- 28409510
TI - Combined osteopathy and exercise management of Achilles tendinopathy in an
athlete.
AB - Mid-portion Achilles tendinopathy is a common injury in sporting populations.
There is conflicting evidence about the best approach to conservative management.
This report focuses on the rehabilitation of an Achilles tendinopathy utilizing
osteopathic manual therapy (OMT) and a structured exercise program in a semi
professional volleyballer. The patient presented with a 4-month history of right
mid-portion Achilles tendon pain that began after a lateral inversion sprain of
the right ankle. The primary complaint was pain impacting the patients vertical
jump performance. The patient complained of pain that was greatest in the morning
and at the beginning of a training session prior to warming up. The inventory
therapy was a combination of OMT. The manual therapy was complemented with a
rehabilitation program. Outcomes were assessed with the Victorian Institute of
Sport Assessment - Achilles (VISA-A), visual analogue scales (VAS), painful arc,
London Hospital Test, soleus lunge test and maximum vertical jump. This case
presented many challenging management options including a resolving right ankle
lateral inversion sprain, a past history of contralateral Achilles tendinopathy
and a high training load. The case demonstrated the importance of patient
centered practice. It was integral that the patient's role as a semi-professional
athlete on the volleyball court was analyzed closely in order to replicate
different facets of his game, so that the rehabilitation program could support a
return to performance at the highest level. Once the initial deficits in mobility
and strength were addressed, the rehabilitation program focus moved to injury
prevention.
PMID- 28409511
TI - Multimodal assessment of sensorimotor shoulder function in patients with
untreated anterior shoulder instability and asymptomatic handball players.
AB - BACKGROUND: Functional evaluation of sensorimotor function of the shoulder joint
is important for guidance of sports-specific training, prevention and
rehabilitation of shoulder instability. Such assessment should be multimodal and
comprise all qualities of sensorimotor shoulder function. This study evaluates
feasibility of such multimodal assessment of glenohumeral sensorimotor function
in patients with shoulder instability and handball players. METHODS: Nine
patients with untreated anterior instability of their dominant shoulder and 15
asymptomatic recreational handball players performed proprioceptive joint
position sense and dynamic stabilization evaluations on an isokinetic device, as
well as a functional throwing performance task. Outcome measures were analysed
individually and equally weighted in a Shoulder-Specific Sensorimotor Index (S
SMI). Finally, isokinetic strength evaluations were conducted. RESULTS: We
observed comparable sensorimotor functions of unstable dominant shoulders
compared to healthy, contralateral shoulders (e.g. P=0.59 for S-SMI). Handball
players demonstrated superior sensorimotor function of their dominant shoulders
exhibiting a significantly higher throwing performance and S-SMI (P<0.001 and
P=0.002, respectively), but comparable internal rotator peak torques for both
shoulders (P>0.22). CONCLUSIONS: The present study proves feasibility of
multimodal assessment of shoulder sensorimotor function in overhead athletes and
patients with symptomatic anterior shoulder instability. Untreated shoulder
instability led to a loss of dominance-related sensorimotor superiority
indicating functional internal rotation deficiency. Dominant shoulders of
handball players showed a superior overall sensorimotor function but weakness of
dominant internal rotation constituting a risk factor for occurrence of posterior
superior impingement syndrome. The S-SMI could serve as a diagnostic tool for
guidance of sports-specific training, prevention and rehabilitation of shoulder
instability.
PMID- 28409512
TI - Immediate effects of different types of stretching exercises on badminton jump
smash.
AB - BACKGROUND: Since different types of stretching exercises may alter athletic
performance, we compared the effects of three types of stretching exercises on
badminton jump smash. METHODS: Sixteen male collegiate badminton players
performed one of three different stretching exercises in a counterbalanced order
on different days. Static stretching had seven typical stretches, while dynamic
stretching involved nine dynamic movements, and resistance dynamic stretching was
performed with weighted vests and dumbbells. Before and after each stretching
exercise, subjects performed 20 trials of jump smashes. Dependent measurements
were the jump heights during jump smashes, velocities of jump-smashed
shuttlecocks, and drop point of jump-smashed shuttlecocks. To test the effects of
each stretching exercise, we performed mixed model ANOVAs and calculated between
time effect sizes (ES). RESULTS: Each stretching exercise improved the jump
heights during jump smashes (type main effect: F(2,75)=1.19, P=0.31; static
stretching: 22.1%, P<0.01, ES=0.98; dynamic stretching: 30.1%, P<0.01, ES=1.49;
resistance dynamic stretching: 17.7%, P=0.03, ES=0.98) and velocities of jump
smashed shuttlecocks (type main effect: F(2,75)=2.18, P=0.12; static stretching:
5.7%, P=0.61, ES=0.39; dynamic stretching: 3.4%, P=0.94, ES=0.28; resistance
dynamic stretching: 6%, P=0.50, ES=0.66). However, there were no differences
among the stretching exercises for any measurement. The drop point of jump
smashed shuttlecocks did not change (interaction: F(2,75)=0.88, P=0.42).
CONCLUSIONS: All stretching exercises improved badminton jump smash performance,
but we could not determine the best protocol. Since badminton requires high-speed
movement and explosive force, we suggest performing dynamic stretching or
resistance dynamic stretching.
PMID- 28409513
TI - Effects of arm insulation on physiological responses during running in the cold.
AB - BACKGROUND: Individuals who exercise outdoors in winter expose themselves to cold
conditions, which have detrimental effects on physiological responses and
exercise performance. Many runners wear arm warmers to protect against cold.
However, the effects of these warmers remain unclear. This study aimed to
determine the effect of arm insulation on physiological responses during running
in a cold environment. METHODS: Twelve healthy men (mean+/-SD age, 22.4+/-3.9
years; height, 1.71+/-0.07 m; mass, 66.9+/-8.1 kg; maximal oxygen consumption,
52.3+/-4.79 mL/kg/min) ran on a treadmill at an intensity of 70% maximal oxygen
consumption for 30 minutes in a climatic chamber at 5 degrees C wearing (ARM) or
not wearing (CON) a tight-fitting polyester sleeve on the forearm. RESULTS:
During the first 10 minutes of exercise, esophageal temperature was significantly
higher (P<0.05) in ARM than in CON. Weighted mean skin temperature was
significantly higher (P<0.05) in ARM than in CON. Thermal sensation was
significantly higher (P<0.05) in ARM than in CON during rest and during the first
10 minutes of exercise. Plasma lactate concentration was significantly lower
(P<0.05) in ARM than in CON at 10 minutes, and plasma norepinephrine
concentration was significantly lower (P<0.05) in ARM than in CON at 10 and 20
minutes. CONCLUSIONS: Higher esophageal temperature and thermal sensation and
lower plasma norepinephrine concentration indicate that arm insulation suppressed
cold stress and attenuated the production of plasma lactate in the early stages
of exercise.
PMID- 28409514
TI - Neck strength and self-reported neck dysfunction: what is the impact of a season
of Rugby Union?
AB - BACKGROUND: Neck strength has been reported to reduce the incidence of
concussions and neck injuries. However, little is known about how neck strength
changes over a playing season. The aim of this study was to understand the impact
a 20-week rugby season has on neck strength, neck pain (NP) and neck stiffness
(NS) in a cohort of rugby players, relative to a non-contact control group.
METHODS: This prospective cohort study employed a fixed-frame dynamometer to
measure neck strength in a simulated contact posture in rugby players (N.=32) and
controls (N.=15). During each assessment, participants performed a single maximal
voluntary contraction in extension, flexion, left (LtFlx) and right lateral
flexion (RtFlx). To quantify neck dysfunction, "current," "average," and "worst"
NP and NS were measured using visual analogue scales. RESULTS: Post-season
improvements (35.3-59.1 N) in neck strength were observed for the forwards for
all measured directions (P<0.01), and were significant when compared to controls.
For the backs, improvements were seen in extension, flexion and LtFlx (P=0.01
0.05), with only extension (29.8 N) and flexion (35.14 N) remaining significant
when contrasted against the controls. The controls' neck strength remained
unchanged over the season. Despite improvements in peak force, NP increased (all
three measures) for the forwards (P=0.01-0.04), while only current (P=0.03) and
worst NP (P=0.04) increased for the backs. Unexpectedly, NS remained unchanged
for the forwards, while backs reported increases for all three measures (P=0.01
0.02). CONCLUSIONS: A season of rugby resulted in neck strength adaptations in
the rugby players. Despite these improvements, increased levels of NP and NS were
reported.
PMID- 28409515
TI - Effects of stretching and fatigue on peak torque, muscle imbalance, and
stability.
AB - BACKGROUND: The present study examined the acute effects of hamstrings stretching
and fatigue on knee extension and flexion peak torque (PT), hamstrings to
quadriceps (H:Q) ratio, and postural stability. METHODS: Seventeen women (mean+/
SD age=21.8+/-2.1 years; body mass=63.0+/-10.5 kg; height=164.7+/-6.2 cm) and
eighteen men (25.8+/-4.6 years; 83.6+/-13.2 kg; 175.3+/-6.0 cm) took part in
three laboratory visits. The first visit was a familiarization session, and the
subsequent two visits were randomly assigned as a control or stretching
condition. For the testing visits, subjects performed a postural stability
assessment, stretched (or sat quietly during the control condition), performed a
50-repetition unilateral isokinetic fatigue protocol, and repeated the postural
stability assessment. RESULTS: There were no significant differences between
control and stretching conditions for initial quadriceps and hamstrings PT,
initial H:Q ratio, quadriceps and hamstrings PT fatigue indexes, H:Q ratio
Fatigue Index, rating of perceived exertion (RPE), or postural stability
(P>0.05). When analyzing 5 intervals of 10 repetitions, significant declines in
quadriceps PT were found in all intervals for both conditions (P<0.05). However,
a decline in hamstrings PT was only found until the fourth interval (i.e.,
repetitions 31 to 40) for the stretching condition (P<0.05). CONCLUSIONS:
Stretching the hamstrings immediately prior to long-duration activities may
eventually cause adverse effects in force-generating capacity of this muscle
group to occur earlier when fatiguing tasks are involved. Nevertheless, no
changes were found for the H:Q ratios after stretching when compared to no
stretching.
PMID- 28409516
TI - Relationships between fitness test and kicking velocity in young soccer players.
AB - BACKGROUND: To study the relation between fitness test and kicking velocity in
young soccer players, which has not been previously studied in this group of age.
METHODS: Ninety-eight Under-11 soccer players who belonged to two professional
Spanish clubs and two amateur clubs were subjected to sprint test (15 and 30
meters), countermovement jump (CMJ), estimation of maximal oxygen intake
(VO2max), kicking velocity test, fatigue index of jump height and
anthropometrical measures. RESULTS: Kicking velocity was significantly correlated
(P<0.05) with 15-m sprint (r=-0.554) and 30-m sprint (r=-0.587), CMJ height
(r=0.479), VO2max (r=0.475), body mass (r=0.311) and height (r=0.529), but not
with Body Mass Index (BMI) (r=-0.011) and Fatigue Index of jump height (r=-0.05).
CONCLUSIONS: This study provides new data about correlations between kicking
velocity and fitness test, establishing greater correlations between kicking
velocity and other variables compared to other groups of age previously studied,
suggesting high transferences between results in fitness test and kicking
velocity.
PMID- 28409517
TI - Could the negative effects of static stretching in warm-up be balanced out by
sport-specific exercise?
AB - BACKGROUND: Static stretching (SS) is widely used in warm-up as it is generally
believed to increase mobility and reduce the risk of injury; however, SS has been
shown to induce transient negative effects on subsequent muscle performance.
Interestingly, recent studies have shown that sport-specific exercise could
restore SS-induced negative effects on certain sports, especially of explosive
muscular performance. Whether sport-specific exercise could restore SS-induced
negative effects on isokinetic muscle performance remains unclear. METHODS: The
present study conducted two different warm-ups: 2-component warm-up and 3
component warm-up on 15 university students. Both protocols contained low
intensity aerobic exercise and sport-specific exercise, whereas the 3-component
warm-up also contained SS which has been previously proven to induce negative
effects on subsequent muscle performance. After the warm-ups, the subjects
performed an isokinetic test on a Biodex. In order to make the sport-specific
exercise mimic the subsequent test, both included concentric isokinetic knee
extension. During the tests, muscle performance of peak torque, mean power, and
total work was recorded. Comparison of the measurements on each parameter between
the two warm-ups was performed using paired t-test. RESULTS: The comparisons did
not reveal any significant difference in the measurement of any parameter between
the two different warm-up protocols, and calculation of Cohen's d revealed small
effect sizes on all of the three variables. CONCLUSIONS: On the basis of the
study results, we concluded that the negative effects of the SS on the variables
were restored by the isokinetic contractions.
PMID- 28409518
TI - Colon epithelial injury in critically ill colectomized patients: aberration of
tight junction proteins and Toll-like receptors.
AB - BACKGROUND: Abnormal permeability and extensive epithelial injury are
characteristic of colon wall damage complicating critical illness, such as
sepsis, and associated with mortality. To assess mechanisms of such colon
epithelial disruption, we studied expression of markers of innate immunity and
intercellular junctions in patients with critical illness. METHODS: Emergency
colectomy samples from 38 intensive care unit patients with sepsis, fulminant C.
difficile colitis, or colon ischemia were studied. Expression of tight junction
proteins (claudin-1, claudin-2, occludin) and Toll-like receptors (TLRs) (TLR2,
TLR4, TLR5, and TLR9) was studied in samples representing histologically verified
damaged segments of the colon, and compared with normal colon (N.=28). RESULTS:
As compared with normal epithelium, histologically damaged samples showed
decreased claudin-1 (P=0.002) expression. Expression of TLR2, TLR4, and TLR5 was
similar in patients and controls, but TLR9 expression was up-regulated in the
histologically damaged region (P=0.03). The expression of other markers (claudin
1, claudin-2, occludin, TLR2,TLR4, TLR5 and TLR9) did not differ between
survivors and non-survivors. CONCLUSIONS: Down-regulation of claudin-1 and up
regulation of TLR9 suggest that epithelial barrier dysfunction and innate
immunity activation are involved in the pathogenesis of colon epithelial injury
in patients with critical illness.
PMID- 28409519
TI - Off-line analysis of electro-anatomical mapping in ventricular arrhythmias.
AB - Sudden cardiac death due to ventricular tachycardia (VT) is a major health issue
in patients with structural heart disease and depressed ejection fraction. If
from one side, implantable cardioverter defibrillator (ICD) therapy has
significantly improved survival of these patients, on the other hand, it has led
to frequent ICD shocks as an emerging problem, being associated with poor quality
of life, frequent hospitalizations and increased mortality. Scar-related re-entry
due to the coexistence of surviving myocardial fibers within fibrotic tissue is
the most common mechanism subtending VT both in ischemic and non-ischemic
cardiomyopathies. In the last two decades, continuous efforts to determine VT
mechanisms and effectively prevent and treat VT with a substrate-based approach
has benefit from off-line analysis of data coming from invasive electroanatomical
mapping as well as from noninvasive imaging modalities such as cardiac magnetic
resonance able to identify the arrhythmic substrate. In this review, we walk over
again established methods for VT substrate characterization and we present
possible applications of new emerging technologies.
PMID- 28409520
TI - Pt/ZnO@C Nanocable with Dual-Enhanced Photocatalytic Performance and Superior
Photostability.
AB - To improve the photocatalytic activity and photostability of ZnO, a novel cable
like Pt/ZnO@C composite is successfully fabricated by coating a 3-5 nm
hydrothermal carbon (HTC) layer on the surface of the Pt nanoparticle-modified
ZnO nanowire. After investigating the optical and photoelectrochemical
performance in detail, it is found that the Pt/ZnO@C nanocable shows a dual
enhanced migration efficiency for the photoinduced surface electrons,
distributing to the modified Pt nanoparticles and the coated HTC layer.
Consequently, the Pt/ZnO@C nanocable exhibits a dual-enhanced photocatalytic
activity for the degradation of various organic pollutants under the UV light
irradiation. The coated HTC layer can also play a role in suspending the ZnO
photocorrosion and significantly improves the photostability of the Pt/ZnO@C
nanocable. Furthermore, the photocatalysis and photocorrosion mechanism of the
Pt/ZnO@C nanocable is proposed and discussed in terms of its structural feature
and photoelectrochemical property. The resultant Pt/ZnO@C nanocable with the
unique HTC layer-coated structure will probably stimulate to design and
synthesize more HTC-hybridized composites with a superior photocatalytic or
photoelectrocatalytic performance.
PMID- 28409521
TI - Corrigendum.
PMID- 28409522
TI - Serological biomarkers as risk factors of SLE-associated pulmonary arterial
hypertension: a systematic review and meta-analysis.
AB - Objective This article aims to determine the serological biomarkers which can be
considered as risk factors of systemic lupus erythematosus (SLE)-associated
pulmonary arterial hypertension by a systematic review and meta-analysis. Methods
This study was conducted in accordance with the PRISMA statement. The search
database included MEDLINE, EMBASE, Cochrane Library and Scopus. The Newcastle
Ottawa scale was used for the quality assessment. The odds ratio was the primary
measure of effect of the risk factors. Results Twelve studies were included in
this meta-analysis. The results identified the anti-RNP antibody and anti-Sm
antibody as risk factors for SLE-associated pulmonary arterial hypertension with
the pooled odds ratios 3.68 (95% confidence interval 2.04-6.63, P < 0.0001) and
1.71 (95% confidence interval 1.06-2.76, P = 0.03), respectively. Conclusion
Pulmonary arterial hypertension is a serious complication of SLE with a worse
prognosis than SLE patients without pulmonary arterial hypertension. The early
recognition of pulmonary arterial hypertension with transthoracic
echocardiography routinely performed in SLE patients with risk factors is
necessary, especially in Asian patients.
PMID- 28409523
TI - Leptin levels in patients with systemic lupus erythematosus inversely correlate
with regulatory T cell frequency.
AB - Leptin levels are increased in patients with systemic lupus erythematosus (SLE)
but little is known on how this correlates with several disease characteristics
including the frequency of regulatory T cells (Tregs). Here we compared serum
leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25
healthy matched controls. Correlations with lupus disease activity were also
analyzed, as well as Treg proliferation potential. It was found that leptin was
remarkably increased in SLE patients as compared to controls, particularly in SLE
patients with moderate and severe active SLE, and the increase correlated with
disease activity. Importantly, increased leptin in lupus patients inversely
correlated with the frequency of Tregs but not in controls, and leptin
neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia
in lupus patients correlates directly with disease activity and inversely with
Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests
possible inhibition of this molecule for an enhanced Treg function in the
disease.
PMID- 28409524
TI - Natural course of untreated cluster headache: A retrospective cohort study.
AB - Objective To determine the natural course of cluster headache. Methods We
screened patients with cluster headache who were diagnosed at Samsung Medical
Center and lost to follow-up for >=5 years. Eligible patients were interviewed by
phone about the longitudinal changes in headache characteristics and disease
course. Remission was defined as symptom-free 1) for longer than twice the
longest between-bout period and 2) for >=5 years. Results Forty-two patients lost
to follow-up for mean 7.5 (range, 5.0-15.7) years were included. The length of
the last bout did not differ from the first one, while the last between-bout
period was longer than the first one ( p = 0.012). Characteristics of cluster
headache decreased over time: Side-locked unilaterality (from 92.9% to 78.9%),
seasonal and circadian rhythmicity (from 63.9% to 60.9% and from 62.2 to 40.5%,
respectively), and autonomic symptoms (from 95.2% to 75.0%). Remission occurred
in 14 (33.3%) patients at a mean age of 42.3 (range, 27-65) years, which was not
different from the age of last bouts in active patients ( p = 0.623). There was a
trend for more seasonal and circadian predilection at baseline in the active
group ( p = 0.056 and 0.063, respectively) and fewer lifetime bouts and shorter
disease duration in patients in remission ( p = 0.063 and 0.090). Conclusions
This study first shows the natural courses of cluster headache. Features of
cluster headache become less prominent over time. Remission occurred regardless
of age. Although no single predictor of remission was found, our data suggest
that remission of cluster headache might not be a consequence of more advanced
age, longer duration of disease, or accumulation of lifetime bouts.
PMID- 28409525
TI - Rare Pyrenophora teres Hybridization Events Revealed by Development of Sequence
Specific PCR Markers.
AB - Pyrenophora teres f. teres and P. teres f. maculata cause net form and spot form,
respectively, of net blotch on barley (Hordeum vulgare). The two forms reproduce
sexually, producing hybrids with genetic and pathogenic variability. Phenotypic
identification of hybrids is challenging because lesions induced by hybrids on
host plants resemble lesions induced by either P. teres f. teres or P. teres f.
maculata. In this study, 12 sequence-specific polymerase chain reaction markers
were developed based on expressed regions spread across the genome. The primers
were validated using 210 P. teres isolates, 2 putative field hybrids (WAC10721
and SNB172), 50 laboratory-produced hybrids, and 7 isolates collected from barley
grass (H. leporinum). The sequence-specific markers confirmed isolate WAC10721 as
a hybrid. Only four P. teres f. teres markers amplified on DNA of barley grass
isolates. Amplified fragment length polymorphism markers suggested that P. teres
barley grass isolates are genetically different from P. teres barley isolates and
that the second putative hybrid (SNB172) is a barley grass isolate. We developed
a suite of markers which clearly distinguish the two forms of P. teres and enable
unambiguous identification of hybrids.
PMID- 28409526
TI - The Impact of "Coat Protein-Mediated Virus Resistance" in Applied Plant Pathology
and Basic Research.
AB - Worldwide, plant viruses cause serious reductions in marketable crop yield and in
some cases even plant death. In most cases, the most effective way to control
virus diseases is through genetically controlled resistance. However, developing
virus-resistant (VR) crops through traditional breeding can take many years, and
in some cases is not even possible. Because of this, the demonstration of the
first VR transgenic plants in 1985 generated much attention. This seminal report
served as an inflection point for research in both basic and applied plant
pathology, the results of which have dramatically changed both basic research and
in a few cases, commercial crop production. The typical review article on this
topic has focused on only basic or only applied research results stemming from
this seminal discovery. This can make it difficult for the reader to appreciate
the full impact of research on transgenic virus resistance, and the contributions
from fundamental research that led to translational applications of this
technology. In this review, we take a global view of this topic highlighting the
significant changes to both basic and applied plant pathology research and
commercial food production that have accumulated in the last 30 plus years. We
present these milestones in the historical context of some of the scientific,
economic, and environmental drivers for developing specific VR crops. The intent
of this review is to provide a single document that adequately records the
significant accomplishments of researchers in both basic and applied plant
pathology research on this topic and how they relate to each other. We hope this
review therefore serves as both an instructional tool for students new to the
topic, as well as a source of conversation and discussion for how the technology
of engineered virus resistance could be applied in the future.
PMID- 28409527
TI - Animal welfare officers in Australian higher education: 3R application, work
contexts, and risk perception.
AB - Acceptance of the concept of replacement, refinement, and reduction (the 3Rs) and
the need for their implementation is widespread in the research community, and is
also backed by local governance requirements in many key jurisdictions. Yet
concerns about underutilization of these concepts and practices remain. From a
survey of animal welfare officers (AWOs) in Australia, the attitudes to, and the
adoption of, 3Rs in Australian public universities is explored. The survey finds
that Australian AWOs have considerable concerns about 3R uptake, with 44%
agreeing that '3R possibilities often remain unused'. At the same time, these
officers see access to relevant information, and the implementation of the 3Rs,
as comparatively easy. Thus, a problem of under-implementation appears to exist.
A number of explanations for this are put forward. AWOs are comparatively junior
professional staff in the Australian university system, constrained from going
beyond basic regulative functions and to the training and promotion of the 3Rs.
When compared with their international counterparts, Australian AWOs spend less
time providing information and advice on the 3Rs to researchers working in their
institutions. Significantly, while AWOs tend to see themselves as being well
supported institutionally, they have comparatively poor relationships with active
researchers who are using animal models. The implications of this are examined,
with recommendations for research institutions, as well as for further research.
PMID- 28409528
TI - Vertebral bone marrow diffusivity in normal adults with varying bone densities at
3T diffusion-weighted imaging.
AB - Background There has been controversy surrounding the relationship between
diffusivity and bone mineral density (BMD) in vertebral bone marrow. Moreover,
sex-related differences of vertebral bone marrow diffusivity in relation to
varying bone densities have not yet been evaluated. Purpose To prospectively
investigate the role of diffusion-weighted imaging (DWI) in assessing vertebral
marrow changes in normal adults with varying bone densities. Material and Methods
A total of 124 normal adult volunteers were enrolled in this study. Sagittal
magnetic resonance (MR) DWI of the lumbar spine was performed. The ADC values of
vertebral bone marrow were measured. Volumetric BMD measurement was performed by
quantitative computed tomography (QCT) using Mindways QCT analysis software. All
participants were divided into three groups according to BMD (normal, osteopenia,
osteoporosis). The differences of the apparent diffusion coefficient (ADC) values
of the three groups was compared, and partial correlation analysis was used to
evaluate the correlation between ADC values and BMD. Results ADC values decreased
as BMD decreased in female participants. When compared with the normal bone
density group, ADC values were significantly decreased in the osteoporotic group
and in the osteopenic group of female participants. ADC values of female
participants were significantly higher than of male participants in the normal
bone density group ( P < 0.001). ADC values correlated positively with BMD values
(r = 0.307, P = 0.016) for female participants. Conclusion The diffusivity in
vertebral bone marrow with varying bone densities differed by sex. ADC values
correlated positively with BMD in women. DWI can quantitively evaluate
osteoporosis in women.
PMID- 28409529
TI - A Determination of Hopelessness and the Perception of Illness in Cancer.
AB - This study was performed with the objective of determining hopelessness and
perception of illness in cancer patients. This was a descriptive and regressional
study. The study was performed between January and June 2014 on 105 outpatients
at the oncology clinic of Manisa Government Hospital in Turkey's western. A
patient information form, the Beck Hopelessness Scale, and the illness perception
questionnaire were used to collect data, and data analysis was performed using
the program Statistical Package for Social Sciences 15.0. Percentages, t test,
Kruskal-Wallis, one-way analysis of variance, and Pearson correlation were used
in the evaluation of research data. The hopelessness levels of cancer patients
participating in the study were at a medium level. As patients' scores on the
hopelessness scale and its subscales increase, so their illness perception scores
also increase. The hopelessness levels of patients whose illness perception was
good were lower; that is, as patients' hopelessness levels fell, their illness
perceptions and view of their illness were affected in a positive way.
PMID- 28409530
TI - Digital stretching of cervix in the active phase of labour to shorten its
duration: a randomised control trial.
AB - An assessment of the efficacy and satisfaction of women in active labour having
digital cervical stretching compared to women who did not have this intervention.
Ours was a randomised controlled trial at a tertiary centre in India. Low-risk
women at term with vertex presentation in active labour with ruptured membranes
and cervical dilation of 4-6 cm were included. Stretching to delivery interval
was 247.5 +/- 158.2 min in the intervention group and 265.5 +/- 158.4 in the
control group. The mode of delivery, incidence of cervical tear, and maternal,
fetal and neonatal complications were similar in both groups. The Labour and
Delivery Satisfaction Index (LADSI) was similar in both groups. While no
significant discomfort was perceived with stretching, it does not appear to
expedite labour.
PMID- 28409531
TI - Procalcitonin levels in sepsis and its association with clinical outcome in
southern India.
AB - Procalcitonin has been found to be a good marker for the diagnosis of sepsis.
However, data on procalcitonin levels to predict the clinical outcome in patients
with sepsis are limited. The aim of our study was to estimate serum procalcitonin
levels in patients with sepsis and to identify its relationship with the clinical
outcome. This was a prospective observational study conducted on 112 patients
with sepsis admitted to the medical wards and medical intensive care unit of a
tertiary care teaching hospital. Serum procalcitonin was measured at baseline
before antibiotic administration and on day 5. The clinical outcome studied was
death or survival on day 28. Baseline mean serum procalcitonin was highest in
patients with septic shock and lowest in patients having sepsis without organ
dysfunction. Mean values of procalcitonin at baseline and on day 5 were
significantly higher in non-survivors when compared with survivors. There was a
significant difference in the change in procalcitonin levels from baseline to day
5 between survivors and non-survivors, with survivors having declining values on
day 5 while non-survivors had increasing values from baseline. The baseline
APACHE II and SOFA scores also showed a significant correlation with the baseline
procalcitonin level. Declining values of procalcitonin therefore indicate a
favourable clinical outcome in patients with sepsis.
PMID- 28409532
TI - Diagnosis of neonatal sepsis using 16S rRNA polymerase chain reaction.
AB - The gold standard for detecting bacterial sepsis is blood culture. However, the
sensitivity of blood culture is low and the results take 48-72 h. Molecular
assays for the detection of bacterial DNA permit early detection of a bacterial
cause as the turnaround time is 6-8 h. We undertook an evaluation of the
performance of universal bacterial primer (16S rRNA) polymerase chain reaction
(PCR) in the diagnosis of neonatal sepsis at a tertiary care medical college
teaching hospital. 16S rRNA PCR was positive in all cases of blood culture proven
sepsis. PCR revealed 95.6% sensitivity, 100% specificity, 100% positive
predictive value and 91.2% negative predictive value and so appears to be a
useful tool for the early diagnosis of bacterial neonatal sepsis.
PMID- 28409533
TI - Control of oxygen tension recapitulates zone-specific functions in human liver
microphysiology systems.
AB - This article describes our next generation human Liver Acinus MicroPhysiology
System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3
microenvironments can be established by controlling the oxygen tension in
individual devices over the range of ca. 3 to 13%. The oxygen tension was
computationally modeled using input on the microfluidic device dimensions,
numbers of cells, oxygen consumption rates of hepatocytes, the diffusion
coefficients of oxygen in different materials and the flow rate of media in the
MicroPhysiology System (MPS). In addition, the oxygen tension was measured using
a ratiometric imaging method with the oxygen sensitive dye, Tris(2,2'-bipyridyl)
dichlororuthenium(II) hexahydrate (RTDP) and the oxygen insensitive dye, Alexa
488. The Zone 1 biased functions of oxidative phosphorylation, albumin and urea
secretion and Zone 3 biased functions of glycolysis, alpha1AT secretion, Cyp2E1
expression and acetaminophen toxicity were demonstrated in the respective Zone 1
and Zone 3 MicroPhysiology System. Further improvements in the Liver Acinus
MicroPhysiology System included improved performance of selected nonparenchymal
cells, the inclusion of a porcine liver extracellular matrix to model the Space
of Disse, as well as an improved media to support both hepatocytes and non
parenchymal cells. In its current form, the Liver Acinus MicroPhysiology System
is most amenable to low to medium throughput, acute through chronic studies,
including liver disease models, prioritizing compounds for preclinical studies,
optimizing chemistry in structure activity relationship (SAR) projects, as well
as in rising dose studies for initial dose ranging. Impact statement Oxygen
zonation is a critical aspect of liver functions. A human microphysiology system
is needed to investigate the impact of zonation on a wide range of liver
functions that can be experimentally manipulated. Because oxygen zonation has
such diverse physiological effects in the liver, we developed and present a
method for computationally modeling and measuring oxygen that can easily be
implemented in all MPS models. We have applied this method in a liver MPS in
which we are then able to control oxygenation in separate devices and demonstrate
that zonation-dependent hepatocyte functions in the MPS recapitulate what is
known about in vivo liver physiology. We believe that this advance allows a deep
experimental investigation on the role of zonation in liver metabolism and
disease. In addition, modeling and measuring oxygen tension will be required as
investigators migrate from PDMS to plastic and glass devices.
PMID- 28409535
TI - Sumoylation E3 Ligase SIZ1 Modulates Plant Immunity Partly through the Immune
Receptor Gene SNC1 in Arabidopsis.
AB - The small ubiqutin-like modifier E3 ligase SIZ1 regulates multiple processes in
Arabidopsis, including salicylic-acid-dependent immune responses. However, the
targets of SIZ1 in plant immunity are not known. Here, we provide evidence that
the plant immune receptor nucleotide-binding leucine-rich repeat gene SNC1
partially mediates the regulation of plant immunity by SIZ1. The siz1 loss-of
function mutant has an autoimmune phenotype that is dependent on SNC1 and
temperature. Overexpression of SIZ1 partially rescues autoimmune mutant
phenotypes induced by activation or overaccumulation of SNC1, and the SNC1
protein amount is attenuated by SIZ1 overexpression. In addition, overexpression
of the F-box protein CPR1 that degrades the SNC1 protein inhibits the growth
defects and disease resistance of the siz1 mutant. Furthermore, we found that the
SNC1 protein is sumoylated in planta. Although it remains to be determined
whether SIZ1 primarily modulates the SNC1 protein via sumoylation or affects SNC1
transcript level, our data indicate that SNC1 is a major mediator of defense
response modulated by SIZ1 and that SNC1 is a crucial target for fine-tuning
plant defense responses.
PMID- 28409536
TI - Improved quality of a vitamin B12-fortified 'ready to blend' fresh-cut mix salad
with chitosan.
AB - A vitamin B12-fortified (0.25 mg L-1) chitosan (10 g L-1) coating was applied to
a ready-to-blend fresh-cut salad including melon, pineapple and carrot, which was
stored at 5 C up to nine days. Uncoated samples were used as control while the
vitamin B12 effect was compared to non-fortified chitosan-coated samples.
Beverages were prepared on blending days 0, 4, 7 and 9 with subsequent storage at
5 C for 0, 24 and 48 h. Physicochemical quality of fresh blended beverages was
well preserved throughout storage. The chitosan coating highly reduced epiphytic
microflora growth and polyphenoloxidase/peroxidase activities. No relevant
variations of total phenolic contents were observed between different fresh
blended beverages. However, its total antioxidant capacity reported after
blending was lower as storage time of ready-to-blend samples increased. Fortified
samples showed a vitamin B12 content of 8.6 ug kg-1 on processing day, ensuring
200 mL of such beverage the recommended daily intake of this vitamin. In
conclusion, a ready-to-blend fruit/vegetable mix, fortified with vitamin B12, was
developed with a shelf life of nine days at 5 C showing the prepared beverages
good quality during subsequent storage for 48 h at 5 C.
PMID- 28409534
TI - Bifidobacterium animalis subsp. lactis 420 mitigates the pathological impact of
myocardial infarction in the mouse.
AB - There is a growing appreciation that our microbial environment in the gut plays a
critical role in the maintenance of health and the pathogenesis of disease.
Probiotic, beneficial gut microbes, administration can directly attenuate cardiac
injury and post-myocardial infarction (MI) remodelling, yet the mechanisms of
cardioprotection are unknown. We hypothesised that administration of
Bifidobacterium animalis subsp. lactis 420 (B420), a probiotic with known anti
inflammatory properties, to mice will mitigate the pathological impact of MI, and
that anti-inflammatory T regulatory (Treg) immune cells are necessary to impart
protection against MI as a result of B420 administration. Wild-type male mice
were administered B420, saline or Lactobacillus salivarius 33 (Ls-33) by gavage
daily for 14 or 35 days, and underwent ischemia/reperfusion (I/R). Pretreatment
with B420 for 10 or 28 days attenuated cardiac injury from I/R and reduced levels
of inflammatory markers. Depletion of Treg cells by administration of anti-CD25
monoclonal antibodies eliminated B420-mediated cardio-protection. Further
cytokine analysis revealed a shift from a pro-inflammatory to an anti
inflammatory environment in the probiotic treated post-MI hearts compared to
controls. To summarise, B420 administration mitigates the pathological impact of
MI. Next, we show that Treg immune cells are necessary to mediate B420-mediated
protection against MI. Finally, we identify putative cellular, epigenetic and/or
post-translational mechanisms of B420-mediated protection against MI.
PMID- 28409537
TI - Impact of pneumococcal conjugate vaccines for children in high- and non-high
income countries.
AB - INTRODUCTION: The high level of effectiveness of pneumococcal conjugate vaccines
(PCVs) was demonstrated initially in high-income countries (HICs). However,
because the burden of pneumococcal diseases (PDs) is greater in non-high-income
countries (NHICs) than HICs, the assessment of these vaccines in this latter
setting is crucial. Areas covered: PubMed was used to search for literature
related to the effectiveness of PCVs. Several studies described the effectiveness
of PCVs in NHICs, and we compare the impact of PCVs on the incidence of invasive
pneumococcal disease (IPD) and pneumonia in HICs and NHICs. Expert commentary:
Implementation of PCVs has been effective in both HICs and NHICs. The decline in
overall incidence of PD is due to the disappearance of most vaccine serotypes,
which is straightforward and comparable across the different settings. As
expected, the decrease in overall incidence of PD was eroded in part by the
increasing incidence of IPD due to non-vaccine serotypes. We need to continue a
multi-faceted surveillance of IPD and carriage.
PMID- 28409538
TI - Prevalence and predictors of severe menopause symptoms among HIV-positive and
negative Nigerian women.
AB - We compared the prevalence of menopause symptoms between women living with HIV to
their HIV-negative peers and determined predictors of severe menopause symptoms
in Jos, Nigeria. This descriptive cross-sectional study included 714 women aged
40-80 years. We compared prevalence and severity of menopause symptoms using the
menopause rating scale (MRS). Logistic regression analysis was used to determine
the predictors of severe symptoms. Six-hundred and seven (85.0%) were HIV
positive, with a mean duration of infection of 5.6 +/- 2.7 years. The mean age of
the cohort was 46 +/- 5 years. The most prevalent menopause symptoms were hot
flushes (67.2%), joint and muscle discomfort (66.2%), physical/mental exhaustion
(65.3%), heart discomfort (60.4%), and anxiety (56.4%). The median MRS score was
higher for HIV-positive compared to HIV-negative women (p = 0.01). Factors
associated with severe menopause symptoms included HIV-positive status (aOR:
3.01, 95% CI: 1.20-7.54) and history of cigarette smoking (aOR: 4.18, 95% CI:
1.31-13.26). Being married (aOR: 0.49, 95% CI: 0.32-0.77), premenopausal (aOR:
0.60, 95% CI: 0.39-0.94), and self-reporting good quality of life (aOR: 0.62. 95%
CI: 0.39-0.98) were protective against severe menopause symptoms. We found HIV
infection, cigarette smoking, quality of life, and stage of the menopause
transition to be associated with severe menopause symptoms. As HIV-positive
populations are aging, additional attention should be given to the reproductive
health of these women.
PMID- 28409539
TI - Particulate matter air pollution from the city of Quito, Ecuador, activates
inflammatory signaling pathways in vitro.
AB - Automobile traffic, industrial processes and natural phenomena cause notable air
pollution, including gaseous and particulate contaminants, in urban centers.
Exposure to particulate matter (PM) air pollution affects human health, and has
been linked to respiratory, cardiovascular and neurological diseases. The
mechanisms underlying inflammation in these diverse diseases, and to what extent
health effects are different for PM obtained from different sources or locations,
are still unclear. This study investigated the in vitro toxicity of ambient
course (PM10) and fine (PM2.5) particulate matter collected at seven sites in the
urban and periurban zones of Quito, Ecuador. Material from all sites was capable
of activating TLR2 and TLR4 signaling pathways, with differences in the
activation related to particle size. Additionally, airborne particulate matter
from Quito is an effective activator of the NLRP3 inflammasome.
PMID- 28409540
TI - Comparison of cellular assays for TLR activation and development of a species
specific reporter cell line for cattle.
AB - PRRs are sentinels of the innate immune system, with TLRs being the most
important. Assays for TLR ligand interactions have been used to gain insights
into their function and signaling pathways. As significant differences exist
between species with regard to ligand recognition, it is necessary to adapt these
tools for TLRs of other species. In the present work, we describe a species
specific cell-based assay adapted for the analysis of single PRRs. Human
embryonic kidney 293T cells were stably transfected with the NF-kappaB-inducible
reporter gene secreted embryonic alkaline phosphatase (SEAP) together with bovine
TLR2. We compared the SEAP response with an existing luciferase NF-kappaB
reporter assay for correlation with IL-8 production. A dose-dependent response
was detected upon stimulation using both methods with good correlation to IL-8
secretion. Lower stimulant concentrations were detected by SEAP assay than IL-8
secretion. The luciferase assay produced high non-specific background for all
ligand concentrations. Of all assays tested, we found the bovine-specific SEAP
reporter assay to be the most convenient and delivered results in the shortest
time. The developed reporter cell line would lend well to rapid, high-throughput
TLR ligand screening for cattle.
PMID- 28409541
TI - A dual positive and negative regulation of monocyte activation by leukocyte Ig
like receptor B4 depends on the position of the tyrosine residues in its ITIMs.
AB - The leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory cell surface
receptor, primarily expressed on mono-myeloid cells. It contains 2 C-type Ig-like
extracellular domains and a long cytoplasmic domain that contains three
intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Data
suggest that LILRB4 suppresses Fc receptor-dependent monocyte functions via its
ITIMs, but relative contributions of the three ITIMs are not characterised. To
address this, tyrosine (Tyr) residues at positions 337, 389 and 419 were single,
double or triple mutated to phenylalanine and stably transfected into a human
monocytic cell line, THP-1. Intact Tyr389 was sufficient to maximally inhibit
FcgammaRI-mediated TNF-alpha production in THP-1 cells, but, paradoxically,
Tyr337 significantly enhanced TNF-alpha production. In contrast, bactericidal
activity was significantly enhanced in mutants containing Tyr419, while Tyr337
markedly inhibited bacteria killing. Taken together, these results indicate that
LILRB4 might have dual inhibitory and activating functions, depending on the
position of the functional tyrosine residues in its ITIMs and/or the nature of
the stimuli.
PMID- 28409542
TI - Inhibitory receptor FcgammaRIIb mediates the effects of IgG on a phagosome
acidification and a sequential dephosphorylation system comprising SHIPs and
Inpp4a.
AB - The relative abundance of phosphoinositide (PI) species on the phagosome membrane
fluctuates over the course of phagocytosis. PtdIns(3,4,5)P3 and PtdIns(3,4)P2
rapidly increase in the forming of the phagocytic cup, following which they
disappear after sealing of the cup. In the present study, we monitored the
clearance of these PI species using the enhanced green fluorescent protein-fused
pleckstrin homology domain of Akt, a fluorescence probe that binds both
PtdIns(3,4,5)P3 and PtdIns(3,4)P2 in Raw 264.7 macrophages. The clearance of PIs
was much faster when the phagocytosed particles were coated with IgG. The effect
of IgG was not observed in the macrophages deficient in FcgammaRIIb, an
inhibitory IgG receptor. To identify the lipid phosphatases responsible for the
FcgammaRIIb-accelerated PI clearance, we prepared a panel of lipid phosphatase
deficient cells. The lack of a PI 5-phosphatase Src homology 2 domain-containing
inositol-5-phosphatase (SHIP)1 or SHIP2 impaired the FcgammaRIIb-accelerated
clearance of PIs. The lack of a PI 4-phosphatase Inpp4a also impaired the
accelerated PIs clearance. In the FcgammaRIIb- and Inpp4a-deficient cells,
acidification of the formed phagosome was slowed. These results suggested that
FcgammaRIIb drives the sequential dephosphorylation system comprising SHIPs and
Inpp4a, and accelerates phagosome acidification.
PMID- 28409543
TI - CCR-2 neutralization augments murine fresh BMC activation by Staphylococcus
aureus via two distinct mechanisms: at the level of ROS production and cytokine
response.
AB - CCR-2 signaling regulates recruitment of monocytes from the bone marrow into the
bloodstream and then to sites of infection. We sought to determine whether CCL
2/CCR-2 signaling is involved in the killing of Staphylococcus aureus by murine
bone marrow cells (BMCs). The intermittent link of reactive oxygen species (ROS)
NF-kappaB/p38-MAPK-mediated CCL-2 production in CCR-2 signaling prompted us to
determine whether neutralization of CCR-2 augments the response of murine fresh
BMCs (FBMCs) after S. aureus infection. It was observed that anti-CCR-2 Ab
treated FBMCs released fewer ROS on encountering S. aureus infection than CCR-2
non-neutralized FBMCs, also correlating with reduced killing of S. aureus in CCR
2 neutralized FBMCs. Staphylococcal catalase and SOD were also found to play a
role in protecting S. aureus from the ROS-mediated killing of FBMC. S. aureus
infection of CCR-2 intact FBMCs pre-treated with either NF-kappaB or p-38-MAPK
blocker induced less CCL-2, suggesting that NF-kappaB or p-38-MAPK is required
for CCL-2 production by FBMCs. Moreover, blocking of CCR-2 along with NF-kappaB
or p-38-MAPK resulted in elevated CCL-2 production and reduced CCR-2 expression.
Inhibition of CCR-2 impairs the response of murine BMCs to S. aureus infection by
attenuation ROS production and modulating the cytokine response.
PMID- 28409544
TI - Hypoxia and the hypoxia-regulated transcription factor HIF-1alpha suppress the
host defence of airway epithelial cells.
AB - Chronic diseases of the respiratory tract, such as cystic fibrosis, are
associated with mucosal and systemic hypoxia. Innate immune functions of airway
epithelial cells are required to prevent and control infections of the lung
parenchyma. The transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha)
regulates cellular adaptation to low oxygen conditions. Here, we show that
hypoxia and HIF-1alpha regulate innate immune mechanisms of cultured human
bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the
prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a
significantly decreased expression of inflammatory mediators (IL-6, IFN-gamma
induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and
Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not
affected by hypoxia or DMOG in the absence of microbial factors. Small
interfering RNA-mediated knockdown of HIF-1alpha in HBECs and in the bronchial
epithelial cell line Calu-3 resulted in increased expression of inflammatory
mediators. The inflammatory response was decreased in lungs of mice stimulated
with inactivated P. aeruginosa under hypoxia. These data suggest that hypoxia
suppresses the innate immune response of airway epithelial cells via HIF-1alpha.
PMID- 28409545
TI - High-affinity caspase-4 binding to LPS presented as high molecular mass
aggregates or in outer membrane vesicles.
AB - Caspases of the non-canonical inflammasome (caspases -4, -5, and -11) directly
bind endotoxin (LOS/LPS) and can be activated in the absence of any co-factors.
Models of LPS-induced caspase activation have postulated that 1:1 binding of
endotoxin monomers to caspase trigger caspase oligomerization and activation,
analogous to that established for endotoxin-induced activation of MD-2/TLR4.
However, using metabolically radiolabeled LOS and LPS, we now show high affinity
and selective binding of caspase-4 to high molecular mass aggregates of purified
endotoxin and to endotoxin-rich outer membrane vesicles without formation of 1:1
endotoxin:caspase complexes. Thus, our findings demonstrate markedly different
endotoxin recognition properties of caspase-4 from that of MD-2/TLR4 and strongly
suggest that activation of caspase-4 (and presumably caspase-5 and caspase-11)
are mediated by interactions with activating endotoxin-rich membrane interfaces
rather than by endotoxin monomers.
PMID- 28409546
TI - Clinical correlation with failure of endovenous therapy for leg swelling.
AB - Background The development and use of minimally invasive procedures provide
improved options for the management of symptoms of chronic venous insufficiency.
While many patients with iliac venous occlusive disease and superficial venous
insufficiency improve with combined iliac venous stenting and correction of
superficial venous reflux, some patients have symptoms which persist. The goal of
this study was to identify clinical factors related to persistent symptoms in
patients with leg swelling after treatment of both iliac vein stenting and
thermal ablation. Methods This observational study analyzed data for patients who
underwent both iliac vein stent placement as well as endovenous ablation (either
RFA or EVLT) as a management for chronic venous insufficiency between February
2012 and February 2014. Follow-up was performed after completion of both
procedures and inquiring for improvement of swelling. Statistical analysis
performed using Chi-square and student's t-test. Results Of the total 173
patients who underwent both endovenous closure and iliac vein stent placements,
55 (31.8%) patients were men; 29 (16%) patients stated they had no improvement
after these procedures. The average age of patients who did not improve was 68.8
(+/-16.7 SD) years and 66.2 (+/-13.3 SD) years for patients who improved. Over
all, the classification of the presenting symptoms by CEAP classification
demonstrated 25.4%, 53.2%, 5.8%, and 15.6%, for C3-C6, respectively. There was no
correlation with failure to improve the swelling with: age ( P = .44), gender ( P
= .33), presenting symptom ( P = .67), use of calcium channel blockers ( P =
.85), nitroglycerin ( P = .86), Plavix ( P = .07), aspirin ( P = .55), Synthyroid
( P = .55), Coumadin ( P = .14), angiotensin receptor blocker ( P = .81), beta
Blockers ( P = .61), angiotensin converting enzyme inhibitors ( P = .88),
furosemide 40 mg ( P = .74), hydrochlorothiazide 12.5 mg ( P = .07),
hydrochlorothiazide 25 mg ( P = .48), and EVLT vs. RFA ( P = .91). The use of
furosemide (20 mg) was associated with continued swelling ( P = .01). The use of
dual diuretics (furosemide and hydrochlorothiazide) was associated with
persistent swelling even after these combined endovenous procedures P = .03).
Conclusion These preliminary data suggest that the treatment with diuretics may
be associated with failure to relieve lower extremity swelling despite combined
endovascular therapy for chronic venous insufficiency.
PMID- 28409547
TI - Long Noncoding RNA XIST Promotes Osteosarcoma Progression by Targeting Ras
Related Protein RAP2B via miR-320b.
AB - Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the
unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific
transcript (XIST) expression is upregulated in several cancers; however, its
underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present
study, we found that XIST expression was significantly increased in OS tissues
and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b
on OS cell proliferation and invasion were studied by MTT and Transwell invasion
assays. The competing relationship between XIST and miR-320b was confirmed by
luciferase reporter assay. Our results showed that XIST knockdown strikingly
inhibited cell proliferation and invasion. Furthermore, XIST could directly bind
to miR-320b and repress miR-320b expression. Moreover, XIST overexpression
significantly relieved the inhibition on OS cell proliferation and invasion
mediated by miR-320b overexpression, which involved the derepression of Ras
related protein RAP2B. We propose that XIST is responsible for OS cell
proliferation and invasion and that XIST exerts its function through the miR
320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate
prognostic biomarker and a target for new therapies in OS patients.
PMID- 28409548
TI - RBMS3 Inhibits the Proliferation and Metastasis of Breast Cancer Cells.
AB - RBMS3, a gene encoding a glycine-rich RNA-binding protein, belongs to the family
of c-Myc gene single-strand binding proteins (MSSP). Recently, several reports
have provided evidence that RBMS3 was deregulated in a diverse range of solid
tumors and played a critical role in tumor progression. However, it remains
unclear whether RBMS3 inhibits the progression of human breast cancer. Thus, the
aim of this study was to investigate the role of RBMS3 in breast cancer and
explore the underlying mechanism in breast cancer progression. Our results
showed, for the first time, that the expression of RBMS3 at both the mRNA and
protein levels was significantly downregulated in human breast cancer tissues and
cell lines. In addition, RBMS3 overexpression dramatically suppressed the
proliferation, migration, and invasion of breast cancer cells in vitro and
attenuated tumor growth in vivo. Furthermore, we observed that RBMS3 greatly
inhibited the protein expression of beta-catenin, cyclin D1, and c-Myc in breast
cancer cells. In summary, we have shown that RBMS3 inhibited the proliferation
and tumorigenesis of breast cancer cells, at least in part, through inactivation
of the Wnt/beta-catenin signaling pathway. Thus, RBMS3 may be a potential
treatment target for breast cancer.
PMID- 28409551
TI - Musculoskeletal Tuberculosis.
AB - Musculoskeletal tuberculosis (TB) accounts for approximately 10% of all
extrapulmonary TB cases in the United States and is the third most common site of
extrapulmonary TB after pleural and lymphatic disease. Vertebral involvement
(tuberculous spondylitis, or Pott's disease) is the most common type of skeletal
TB, accounting for about half of all cases of musculoskeletal TB. The
presentation of musculoskeletal TB may be insidious over a long period and the
diagnosis may be elusive and delayed, as TB may not be the initial consideration
in the differential diagnosis. Concomitant pulmonary involvement may not be
present, thus confusing the diagnosis even further. Early diagnosis of bone and
joint disease is important to minimize the risk of deformity and enhance outcome.
The introduction of newer imaging modalities, including MRI (imaging procedure of
choice) and CT, has enhanced the diagnostic evaluation of patients with
musculoskeletal TB and for directed biopsies of affected areas of the
musculoskeletal system. Obtaining appropriate specimens for culture and other
diagnostic tests is essential to establish a definitive diagnosis and recover M.
tuberculosis for susceptibility testing. A total of 6 to 9 months of a rifampin
based regimen, like treatment of pulmonary TB, is recommended for the treatment
of drug susceptible musculoskeletal disease. Randomized trials of tuberculous
spondylitis have demonstrated that such regimens are efficacious. These data and
those from the treatment of pulmonary TB have been extrapolated to form the basis
of treatment regimen recommendations for other forms of musculoskeletal TB.
PMID- 28409552
TI - Long Noncoding RNA PVT1 Promotes Melanoma Progression via Endogenous Sponging miR
26b.
AB - Melanoma is an extremely aggressive malignant skin tumor with a high mortality.
Various long noncoding RNAs (lncRNAs) have been reported to be associated with
the oncogenesis of melanoma. The purposes of this study were to investigate the
potential role of lncRNA PVT1 in melanoma progression and to explore its possible
mechanisms. A total of 35 patients who were diagnosed with malignant melanoma
were enrolled in this study. Expression of PVT1 was significantly upregulated in
melanoma tissue and was associated with a poor prognosis. Loss-of-function
experiments showed that PVT1 knockdown markedly suppressed the proliferation
activity, induced cell cycle arrest at the G0/G1 phase, and enhanced the
apoptosis of melanoma cell lines. Bioinformatics analysis and dual-luciferase
reporter assay revealed that PVT1 directly bound to miR-26b, which had been
verified to be a tumor suppressor in melanoma. Moreover, further functional
rescue experiments revealed that PVT1 knockdown could observably reverse the
tumor-promoting role of the miR-26b inhibitor. Overall, our study demonstrates
the oncogenic role of PVT1 as a miR-26b sponge, possibly providing a novel
therapeutic target for melanoma.
PMID- 28409553
TI - The Thyromimetic KB2115 (Eprotirome) Induces Rat Hepatocyte Proliferation.
AB - Although the hepatomitogenic activity of T3 is well established, the wide range
of harmful effects exerted by this hormone precludes its use in regenerative
therapy. The aim of this study was to investigate whether an agonist of TRbeta,
KB2115 (Eprotirome), could exert a mitogenic effect in the liver, without most of
the adverse T3/TRalpha-dependent side effects. F-344 rats treated with KB2115 for
1 week displayed a massive increase in bromodeoxyuridine incorporation (from 20%
to 40% vs. 5% of controls), which was associated with increased mitotic activity
in the absence of significant signs of liver toxicity. Noteworthy, while cardiac
hypertrophy typical of T3 was not observed, beneficial effects, such as lowering
blood cholesterol levels, were associated to KB2115 administration. Following a
single dose of KB2115, hepatocyte proliferation was evident as early as 18 h,
demonstrating its direct mitogenic effect. No increase in serum transaminase
levels or apoptosis was observed prior to or concomitantly with the S phase.
While KB2115-induced mitogenesis was not associated to enhance expression of c
fos, c-jun, and c-myc, cyclin D1 levels rapidly increased. In conclusion, KB2115
induces hepatocyte proliferation without overt toxicity. Hence, this agent may be
useful for regenerative therapies in liver transplantation or other surgical
settings.
PMID- 28409554
TI - The lncRNA CCAT1 Upregulates Proliferation and Invasion in Melanoma Cells via
Suppressing miR-33a.
AB - It is increasingly evident that various long noncoding RNAs (lncRNAs) participate
in the tumorigenesis of multiple tumors, including melanoma. lncRNAs have been
validated as oncogenic factors in various tumors; however, the potential
regulatory mechanism of CCAT1 in melanoma is still unclear. The purpose of this
study was to investigate the regulation of CCAT1 on melanoma genesis. The
expression of CCAT1 in melanoma tissue and cell lines was measured using qRT-PCR.
Interference oligonucleotide or mimic sequences were applied to up- or
downregulate RNA expression. CCK-8 and colony formation assays were performed to
detect the proliferation capability. Transwell assay was used to assess the
migration and invasion capacities. Bioinformatics analysis was performed to
predict the target miRNAs of CCAT1. Expression of CCAT1 was significantly
upregulated in melanoma tissue and cell lines. CCAT1 knockdown observably
suppressed the proliferation, migration, and invasion abilities. Bioinformatics
analysis predicted that miR-33a acted as a target of CCAT1, which was confirmed
by dual-luciferase reporter assay. CCAT1 knockdown reversed the tumor-promoting
ability of the miR-33a inhibitor. CCAT1 acts as an oncogenic factor in the
genesis of melanoma and exerts tumor-promoting roles via sponging miR-33a,
providing a novel insight for competing endogenous RNA (ceRNA) in the
tumorigenesis of melanoma.
PMID- 28409555
TI - Treatment of Latent Tuberculosis Infection.
AB - There are approximately 56 million people who harbor Mycobacterium tuberculosis
that may progress to active tuberculosis (TB) at some point in their lives.
Modeling studies suggest that if only 8% of these individuals with latent TB
infection (LTBI) were treated annually, overall global incidence would be 14-fold
lower by 2050 compared to incidence in 2013, even in the absence of additional TB
control measures. This highlights the importance of identifying and treating
latently infected individuals, and that this intervention must be scaled up to
achieve the goals of the Global End TB Strategy. The efficacy of LTBI treatment
is well established, and the most commonly used regimen is 9 months of daily self
administered isoniazid. However, its use has been hindered by limited provider
awareness of the benefits, concern about potential side effects such as
hepatotoxicity, and low rates of treatment completion. There is increasing
evidence that shorter rifamycin-based regimens are as effective, better
tolerated, and more likely to be completed compared to isoniazid. Such regimens
include four months of daily self-administered rifampin monotherapy, three months
of once weekly directly observed isoniazid-rifapentine, and three months of daily
self-administered isoniazid-rifampin. The success of LTBI treatment to prevent
additional TB disease relies upon choosing an appropriate regimen individualized
to the patient, monitoring for potential adverse clinical events, and utilizing
strategies to promote adherence. Safer, more cost-effective, and more easily
completed regimens are needed and should be combined with interventions to better
identify, engage, and retain high-risk individuals across the cascade from
diagnosis through treatment completion of LTBI.
PMID- 28409556
TI - Knockdown of TMPRSS3, a Transmembrane Serine Protease, Inhibits Proliferation,
Migration, and Invasion in Human Nasopharyngeal Carcinoma Cells.
AB - TMPRSS3 belongs to the large type II transmembrane serine protease (TTSP) family,
which plays an important role in the development and progression of tumors.
However, the function of TMPRSS3 in nasopharyngeal carcinoma (NPC) remains
unclear. The present study aimed to examine the impact of TMPRSS3 on the
proliferation, migration, and invasion of NPC cells and their potential
mechanisms. Our results demonstrated that the expression of TMPRSS3 was obviously
upregulated in human NPC tissues and cell lines. Knockdown of TMPRSS3 expression
significantly suppressed the proliferation and tumorigenicity of NPC cells in
vitro and in vivo. Furthermore, knockdown of TMPRSS3 inhibited migration and
invasion, as well as prevented the EMT process in NPC cells. Finally, knockdown
of TMPRSS3 attenuated activation of the PI3K/Akt signaling pathway in NPC cells.
Taken together, the present study demonstrates that the knockdown of TMPRSS3
inhibits proliferation, migration, and invasion in human NPC cells through the
inactivation of the PI3K/Akt signaling pathway. This study suggests that TMPRSS3
may be a potential therapeutic target for the treatment of NPC.
PMID- 28409557
TI - Randomised controlled trial of silk therapeutic garments for the management of
atopic eczema in children: the CLOTHES trial.
AB - BACKGROUND: Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition
that affects the quality of life of children and their families. The role of
specialist clothing in the management of AE is poorly understood. OBJECTIVES: To
assess the effectiveness and cost-effectiveness of silk garments for the
management of AE in children with moderate to severe disease. DESIGN: Parallel
group, observer-blind, randomised controlled trial of 6 months' duration,
followed by a 2-month observational period. A nested qualitative study evaluated
the beliefs of trial participants, health-care professionals and health-care
commissioners about the use of silk garments for AE. SETTING: Secondary care and
the community in five UK centres. PARTICIPANTS: Children aged 1-15 years with
moderate or severe AE. INTERVENTIONS: Participants were randomised (1 : 1 using
online randomisation) to standard care or standard care plus 100% silk garments
made from antimicrobially protected knitted sericin-free silk [DermaSilkTM
(AlPreTec Srl, San Dona di Piave, Italy) or DreamSkinTM (DreamSkin Health Ltd,
Hatfield, UK)]. Three sets of garments were supplied per participant, to be worn
for up to 6 months (day and night). At 6 months the standard care group received
the garments to use for the remaining 2-month observational period. MAIN OUTCOME
MEASURES: Primary outcome - AE severity using the Eczema Area and Severity Index
(EASI) assessed at 2, 4 and 6 months, by nurses blinded to treatment allocation.
EASI scores were log-transformed for analysis. Secondary outcomes - patient
reported eczema symptoms (Patient Oriented Eczema Measure); global assessment of
severity (Investigator Global Assessment); quality of life of the child (Atopic
Dermatitis Quality of Life, Child Health Utility - 9 Dimensions), family
(Dermatitis Family Impact Questionnaire) and main carer (EuroQoL-5 Dimensions-3
Levels); use of standard eczema treatments (e.g. emollients, topical
corticosteroids); and cost-effectiveness. The acceptability and durability of the
clothing, and adherence to wearing the garments, were assessed by parental/carer
self-report. Safety outcomes - number of skin infections and hospitalisations for
AE. RESULTS: A total of 300 children were randomised (26 November 2013 to 5 May
2015): 42% female, 79% white, mean age 5 years. The primary analysis included 282
out of 300 (94%) children (n = 141 in each group). Garments were worn for at
least 50% of the time by 82% of participants. Geometric mean EASI scores at
baseline, 2, 4 and 6 months were 8.4, 6.6, 6.0, 5.4 for standard care and 9.2,
6.4, 5.8, 5.4 for silk clothing, respectively. There was no evidence of
difference between the groups in EASI score averaged over all follow-up visits
adjusted for baseline EASI score, age and centre (ratio of geometric means 0.95,
95% confidence interval 0.85 to 1.07; p = 0.43). This confidence interval is
equivalent to a difference of -1.5 to 0.5 in the original EASI scale units. Skin
infections occurred in 39 out of 141 (28%) and 36 out of 142 (25%) participants
for standard care and silk clothing groups, respectively. The incremental cost
per QALY of silk garments for children with moderate to severe eczema was L56,811
from a NHS perspective in the base case. Sensitivity analyses supported the
finding that silk garments do not appear to be cost-effective within currently
accepted thresholds. LIMITATIONS: Knowledge of treatment allocation may have
affected behaviour and outcome reporting for some of the patient-reported
outcomes. CONCLUSIONS: The addition of silk garments to standard AE care is
unlikely to improve AE severity, or to be cost-effective compared with standard
care alone, for children with moderate or severe AE. This trial adds to the
evidence base to guide clinical decision-making. FUTURE WORK: Non-pharmacological
interventions for the management of AE remain a research priority among patients.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN77261365. FUNDING: This
project was funded by the National Institute for Health Research (NIHR) Health
Technology Assessment programme and will be published in full in Health
Technology Assessment; Vol. 21, No. 16. See the NIHR Journals Library website for
further project information.
PMID- 28409558
TI - In vitro detection of cholangiocarcinoma cells using a fluorescent protein
expressing oncolytic herpes virus.
AB - Pathological confirmation is desired prior to high-risk surgery for suspected
perihilar cholangiocarcinoma (PHC), but preoperative tissue diagnosis is limited
by poor sensitivity of available techniques. This study aimed to validate whether
a tumor-specific enhanced green fluorescent protein (eGFP)-expressing oncolytic
virus could be used for cholangiocarcinoma (CC) cell detection. Extrahepatic CC
cell lines SK-ChA-1, EGI-1, TFK-1 and control cells (primary human liver cells)
were exposed to the oncolytic herpes simplex type 1 virus NV1066 for up to 24 h
in adherent culture. The technique was validated for cells in suspension and
cultured cells that had been exposed to crude patient bile. Optimal incubation
time of the CC cells with NV1066 at a multiplicity of infection of 0.1 was
determined at 6-8 h, yielding 15% eGFP-expressing cells, as measured by flow
cytometry. Cells were able to survive 2-h crude bile exposure and remained
capable of producing eGFP following NV1066 infection. Detection of malignant
cells was possible at the highest dilution tested (10 CC cells among 2 * 105
control cells), though hampered by non-target cell autofluorescence. The
technique was not applicable to cells in suspension due to insufficient eGFP
production. Accordingly, as yet the technique is not suitable for standardized
clinical diagnostics in PHC.
PMID- 28409559
TI - Correlations of MGMT genetic polymorphisms with temozolomide resistance and
prognosis of patients with malignant gliomas: a population-based study in China.
AB - This study aims to investigate the associations of O6-methylguanine-DNA
methyltransferase (MGMT) genetic polymorphisms (Leu84Phe and Ile143Val) with
temozolomide (TMZ) resistance and prognosis of patients with malignant gliomas. A
total of 212 patients diagnosed with malignant gliomas were enrolled in this
study as the case group. All of these patients took oral TMZ and were assigned
into the TMZ-sensitive (complete response+partial response) and the TMZ-resistant
(stable disease+progressive disease) groups based on the clinical response after
chemotherapy. The polymerase chain reaction-restriction fragment length
polymorphism was used to identify the gene polymorphism of Leu84Phe and
Ile143Val. The survival time and survival outcomes of all the patients were
obtained by follow-up. There were significant differences in the genotype and
allele of Leu84Phe between the TMZ-sensitive and the TMZ-resistant groups. The
CT, TT and CT+TT genotypes and the T allele of MGMT gene Leu84Phe may be
associated with increasing TMZ resistance in patients with malignant gliomas.
Logistic regression analysis showed that Leu84Phe of MGMT gene and pathological
grade were independent risk factors for the increase of TMZ resistance in
patients with malignant gliomas. Kaplan-Meier survival curve revealed that the
average survival time of patients with the CT+TT and CC genotypes of Leu84Phe in
the two groups was statistically significant. COX regression analysis showed that
Leu84Phe, degree of resection and pathological grade were independent prognostic
factors for patients with malignant gliomas. Our study demonstrates that Leu84Phe
of MGMT gene might be a risk factor of TMZ resistance and poor prognosis of
patients with malignant gliomas.
PMID- 28409560
TI - Identification of differentially expressed genes and their upstream regulators in
colorectal cancer.
AB - To identify the differentially expressed genes (DEGs) and their transcription
factors (TFs) in colorectal cancer (CRC). We performed an integrated analysis of
microarray studies. Functional annotation and CRC-specific transcriptional
regulatory network construction were performed. Expression of selected DEGs and
TFs was verified with The Cancer Genome Atlas (TCGA) data sets and qRT-PCR.
SurvMicro was used to analyze the correlation between the overall survival time
of CRC patients and the expression of DEGs and TFs. Seven data sets were obtained
and 2014 DEGs in CRC were identified. Pathways in cancer and fatty acid
metabolism were significantly enriched pathways of upregulated and downregulated
DEGs, respectively. Expression of five DEGs (RERGL, ESM1, CA1, ANGPTL7 and
TMEFF2) and their five TFs (ZNF354C, ARID3A, NFIC, BRCA1 and ZEB1) was verified
by TCGA data sets and qRT-PCR. Their expression in TCGA data sets was same as
that in our integrated analysis. Only the expression of EMS1, NFIC, BRCA1 and
ZEB1 was inconsistent with integrated analysis and TCGA data sets. Expression of
RERGL and BRCA1 was significantly correlated with the overall survival time of
CRC patients. These five DEGs may have roles in CRC regulated by their five
upstream TFs, which may make a contribution in uncovering the mechanism and
providing new strategy of diagnosis and therapies for CRC.
PMID- 28409561
TI - The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in
women with metastatic breast cancer: a systematic review of clinical trials.
AB - Despite benefits of systemic chemotherapy in breast cancer treatment, several
patients with early-stage breast cancer will develop metastatic breast cancer
(MBC). Doxorubicin is among the most active agents against MBC. However, the use
of doxorubicin is related to some life-threatening side effects including
cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin
and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product
claimed to achieve these two objectives because of its different pharmacokinetic
profile. The aim of this study was to determine the side-effect profile of PLD in
MBC through a systematic review of phase II clinical trials. A literature search
in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical
systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to
the inclusion criteria. Reported hematological and non-hematological side effects
were categorized. Out of 718 articles that were initially identified, 8 were in
accordance with the inclusion criteria. We found that the most important side
effects of PLD were skin toxicity and mucositis, but the proportion of patients
who showed grade III and IV of these side effects was relatively low. On the
other hand, the occurrence of cardiotoxicity, the most important problem with
doxorubicin, was considerably reduced in patients treated with PLD. Although PLD
has demonstrated a lower toxicity profile than conventional anthracyclines, it
has also new side effects. However, it seems that the reduced cardiotoxicity of
PLD has made it a more appropriate option in patients with MBC, especially in
those with risk factors for cardiac diseases.
PMID- 28409562
TI - Chemotherapy-induced intestinal inflammatory responses are mediated by exosome
secretion of double-strand DNA via AIM2 inflammasome activation.
AB - Chemotherapies are known often to induce severe gastrointestinal tract toxicity
but the underlying mechanism remains unclear. This study considers the widely
applied cytotoxic agent irinotecan (CPT-11) as a representative agent and
demonstrates that treatment induces massive release of double-strand DNA from the
intestine that accounts for the dose-limiting intestinal toxicity of the
compound. Specifically, "self-DNA" released through exosome secretion enters the
cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2)
inflammasome. This leads to mature IL-1beta and IL-18 secretion and induces
intestinal mucositis and late-onset diarrhoea. Interestingly, abrogation of AIM2
signalling, either in AIM2-deficient mice or by a pharmacological inhibitor such
as thalidomide, significantly reduces the incidence of drug-induced diarrhoea
without affecting the anticancer efficacy of CPT-11. These findings provide
mechanistic insights into how chemotherapy triggers innate immune responses
causing intestinal toxicity, and reveal new chemotherapy regimens that maintain
anti-tumour effects but circumvent the associated adverse inflammatory response.
PMID- 28409563
TI - Glutamate in Pediatric Obsessive-Compulsive Disorder and Response to Cognitive
Behavioral Therapy: Randomized Clinical Trial.
AB - Cognitive-behavioral therapy (CBT) is effective for pediatric obsessive
compulsive disorder (OCD), but non-response is common. Brain glutamate (Glu)
signaling may contribute to OCD pathophysiology and moderate CBT outcomes. We
assessed whether Glu measured with magnetic resonance spectroscopy (MRS) was
associated with OCD and/or CBT response. Youths aged 7-17 years with DSM-IV OCD
and typically developing controls underwent 3 T proton echo-planar spectroscopic
imaging (PEPSI) MRS scans of pregenual anterior cingulate cortex (pACC) and
ventral posterior cingulate cortex (vPCC)-regions possibly affected by OCD-at
baseline. Controls returned for re-scan after 8 weeks. OCD youth-in a randomized
rater-blinded trial-were re-scanned after 12-14 weeks of CBT or after 8 weeks of
minimal-contact waitlist; waitlist participants underwent a third scan after
crossover to 12-14 weeks of CBT. Forty-nine children with OCD (mean age 12.2+/
2.9 years) and 29 controls (13.2+/-2.2 years) provided at least one MRS scan. At
baseline, Glu did not differ significantly between OCD and controls in pACC or
vPCC. Within controls, Glu was stable from scan-to-scan. Within OCD subjects, a
treatment-by-scan interaction (p=0.034) was observed, driven by pACC Glu dropping
19.5% from scan-to-scan for patients randomized to CBT, with minor increases
(3.8%) for waitlist participants. The combined OCD participants (CBT-only plus
waitlist-CBT) also showed a 16.2% (p=0.004) post-CBT decrease in pACC Glu. In the
combined OCD group, within vPCC, lower pre-CBT Glu predicted greater post-CBT
improvement in symptoms (CY-BOCS; r=0.81, p=0.00025). Glu may be involved in the
pathophysiology of OCD and may moderate response to CBT.
PMID- 28409564
TI - Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain
Activation, OPRM1 Genotype, and Smoking Status.
AB - Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs),
but it is not effective for everyone. Variability in its effects on reward
related brain activation, genetic variation, and/or cigarette smoking may account
for this mixed response profile. This randomized clinical trial tested the
effects of naltrexone on drinking and alcohol cue-elicited brain activation,
evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and
explored whether the effects of medication on cue-elicited activation predicted
subsequent drinking. One hundred and fifty-two treatment-seeking individuals with
alcohol dependence, half preselected to carry at least one A118G G (Asp) allele,
were randomized to naltrexone (50 mg) or placebo for 16 weeks and administered an
fMRI alcohol cue reactivity task at baseline and after 2 weeks of treatment.
Naltrexone, relative to placebo, significantly reduced alcohol cue-elicited
activation of the right ventral striatum (VS) between baseline and week 2 and
reduced heavy drinking over 16 weeks. OPRM1 genotype did not significantly
moderate these effects, but G-allele carriers who received naltrexone had an
accelerated return to heavy drinking after medication was stopped. Smoking
moderated the effects of medication on drinking, such that naltrexone was
superior to placebo only among smokers. The degree of reduction in right VS
activation between scans interacted with medication in predicting subsequent
drinking, such that individuals with greater reduction in activation who received
naltrexone, but not placebo, experienced the least heavy drinking during the
following 14 weeks. These data replicate previous findings that naltrexone
reduces heavy drinking and reward-related brain activation among treatment
seeking individuals with AUDs, and indicate that smoking and the magnitude of
reduction in cue-elicited brain activation may predict treatment response.
PMID- 28409565
TI - Can Pornography be Addictive? An fMRI Study of Men Seeking Treatment for
Problematic Pornography Use.
AB - Pornography consumption is highly prevalent, particularly among young adult
males. For some individuals, problematic pornography use (PPU) is a reason for
seeking treatment. Despite the pervasiveness of pornography, PPU appears under
investigated, including with respect to the underlying neural mechanisms. Using
functional magnetic resonance imaging (fMRI), we examined ventral striatal
responses to erotic and monetary stimuli, disentangling cue-related 'wanting'
from reward-related 'liking' among 28 heterosexual males seeking treatment for
PPU and 24 heterosexual males without PPU. Subjects engaged in an incentive delay
task in the scanner, in which they received erotic or monetary rewards preceded
by predictive cues. Blood-oxygen-level-dependent responses to erotic and monetary
cues were analyzed and examined with respect to self-reported data on sexual
activity collected over the 2 preceding months. Men with and without PPU differed
in their striatal responses to cues predicting erotic pictures but not in their
responses to erotic pictures. PPU subjects when compared with control subjects
showed increased activation of ventral striatum specifically for cues predicting
erotic pictures but not for cues predicting monetary gains. Relative sensitivity
to cues predicting erotic pictures vs monetary gains was significantly related to
the increased behavioral motivation to view erotic images (suggestive of higher
'wanting'), severity of PPU, amount of pornography use per week, and number of
weekly masturbations. Our findings suggest that, similar to what is observed in
substance and gambling addictions, the neural and behavioral mechanisms
associated with the anticipatory processing of cues specifically predicting
erotic rewards relate importantly to clinically relevant features of PPU. These
findings suggest that PPU may represent a behavioral addiction and that
interventions helpful in targeting behavioral and substance addictions warrant
consideration for adaptation and use in helping men with PPU.
PMID- 28409566
TI - Combined Effects of Glucocorticoid and Noradrenergic Activity on Loss Aversion.
AB - Loss aversion is a well-known behavioral regularity in financial decision making,
describing humans' tendency to overweigh losses compared to gains of the same
amount. Recent research indicates that stress and associated hormonal changes
affect loss aversion, yet the underlying neuroendocrine mechanisms are still
poorly understood. Here, we investigated the causal influence of two major stress
neuromodulators, cortisol and noradrenaline, on loss aversion during financial
decision making. In a double-blind, placebo-controlled between-subject design, we
orally administered either the alpha2-adrenergic antagonist yohimbine (increasing
noradrenergic stimulation), hydrocortisone, both substances, or a placebo to
healthy young men. We tested the treatments' influence on a financial decision
making task measuring loss aversion and risk attitude. We found that both drugs
combined, relative to either drug by itself, reduced loss aversion in the absence
of an effect on risk attitude or choice consistency. Our data suggest that
concurrent glucocorticoid and noradrenergic activity prompts an alignment of
reward- with loss-sensitivity, and thus diminishes loss aversion. Our results
have implications for the understanding of the susceptibility to biases in
decision making.
PMID- 28409568
TI - Reply to Magaret and Wald, "Autism Link to Herpes Simplex Virus 2 Antibody in
Pregnancy Likely To Be Spurious".
PMID- 28409569
TI - Erratum to: A novel octavalent combined Erysipelas, Parvo and Leptospira vaccine
provides (cross) protection against infection following challenge of pigs with 9
different Leptospira interrogans serovars.
AB - [This corrects the article DOI: 10.1186/s40813-015-0011-0.].
PMID- 28409567
TI - SF3B1 and BAP1 mutations in blue nevus-like melanoma.
AB - Blue nevi are melanocytic tumors originating in the cutaneous dermis. Malignant
tumors may arise in association with or resembling blue nevi, so called 'blue
nevus-like melanoma', which can metastasize and result in patient death.
Identifying which tumors will behave in a clinically aggressive manner can be
challenging. Identifying genetic alterations in such tumors may assist in their
diagnosis and prognostication. Blue nevi are known to be genetically related to
uveal melanomas (eg, both harboring GNAQ and GNA11 mutations). In this study, we
analyzed a large cohort (n=301) of various morphologic variants of blue nevi and
related tumors including tumors diagnosed as atypical blue nevi (n=21), and blue
nevus-like melanoma (n=12), screening for all gene mutations known to occur in
uveal melanoma. Similar to published reports, we found the majority of blue nevi
harbored activating mutations in GNAQ (53%) or GNA11 (15%). In addition, rare
CYSLTR2 (1%) and PLCB4 (1%) mutations were identified. EIF1AX, SF3B1, and BAP1
mutations were also detected, with BAP1 and SF3B1 R625 mutations being present
only in clearly malignant tumors (17% (n=2) and 25% (n=3) of blue nevus-like
melanoma, respectively). In sequencing data from a larger cohort of cutaneous
melanomas, this genetic profile was also identified in tumors not originally
diagnosed as blue nevus-like melanoma. Our findings suggest that the genetic
profile of coexistent GNAQ or GNA11 mutations with BAP1 or SF3B1 mutations can
aid the histopathological diagnosis of blue nevus-like melanoma and distinguish
blue nevus-like melanoma from conventional epidermal-derived melanomas. Future
studies will need to further elucidate the prognostic implications and
appropriate clinical management for patients with tumors harboring these mutation
profiles.
PMID- 28409570
TI - [The tabernacle head does not hurt? Storage and distribution of the digital
image].
AB - Modern life sciences become quantitative. Images created by microscopy are
therefore the objects of measurement rather than a simple pictures. Saving and
further storage of such images cannot change future measurements on them. Such
images are the integral part of experiments. Present article try to describe what
kind of data we are talking about, how should we store them and how we should
not.
PMID- 28409571
TI - [Getting an insight into the brain - new optical clearing techniques and imaging
using light-sheet microscope].
AB - One of the biggest challenges in neuroscience is to understand how brain
operates. For this, it would be the best to image the whole brain with at least
cellular resolution, preserving the three-dimensional structure in order to
capture the connections between different areas. Most currently available high
resolution imaging techniques are based on preparing thin brain sections that are
next photographed one by one and subsequently bigger structures are
reconstructed. These techniques are laborious and create artifacts. Recent
optical clearing methods allow to obtain literally transparent brains that can be
imaged using light-sheet microscope. The present review summarizes the most
popular optical clearing techniques, describing their different mechanisms and
comparing advantages and disadvantages of different approaches, and presents the
principle of light-sheet microscopy and its use in imaging. Finally, it gives
examples of application of optical tissue clearing and light-sheet imaging in
neuroscience and beyond it.
PMID- 28409572
TI - [FRET-based biosensors in cell migration research].
AB - Cell migration is a complicated process, which is crucial for functioning of
multicellular organisms. Multiple signalling pathways are deeply involved in the
precise control of consecutive cell migration stages based on remodelling of the
actin cytoskeleton. Small Rho GTPases (RhoA, Rac1 and Cdc42) as well as multiple
protein and lipid kinases, calcium ions and mechanosensors are crucial components
in this process. Exploration of those complicated correlations is possible with
constant advancement of fluorescence microscopy. A significant progress in this
field has been achieved since discovery of fluorescent proteins and subsequently
FRET-based biosensors. Such protein constructs react with a change of FRET
efficiency in response to the particular protein activity change. Properly
designed and regularly improved biosensors offer the possibility of real-time
imaging of signalling pathways dynamics in migrating cells. The perception of Rho
GTPases involvement and some other signalling pathways connected with cell
migration have been clarified with multiple experiments already carried out with
such FRET-based biosensors.
PMID- 28409573
TI - [Microscopic imaging of calcium ions with genetically encoded calcium
indicators].
AB - Calcium is a second messenger that plays a key role in various cellular
processes. Monitoring calcium levels is a prerequisite to their understanding.
The first calcium indicators for microscopy were the luminescent protein aequorin
and chemical probes. These indicators, however, have serious drawbacks, limiting
their use in many types of experiments. Cloning of cDNA for the A. victoria GFP
and creation of its first spectral variants has initiated the development of
fluorescent, genetically encoded calcium indicators (GECI). They are composed of
a fluorescent protein and a calcium-binding protein, usually calmodulin. The
binding of calcium to the sensory domain of the indicator affects the fluorescent
properties of the chromophore, which enables recording of calcium signals as
fluorescent light. GECIs have many advantages and are essential for conducting
long-term experiments in vivo. This article gives an overview of the currently
available GECIs, the history of their development, applications and microscopic
imaging systems.
PMID- 28409574
TI - [Watching dance of the molecules - CARS microscopy].
AB - CARS (Coherent Anti-Stokes Raman Scattering) microscopy is an imaging method for
living cells visualization as well as for food or cosmetics material analysis
without the need for staining. The near infrared laser source generates the CARS
signal - the characteristic intrinsic vibrational contrast of the molecules in a
sample which is no longer caused by staining, but by the molecules themselves. It
provides the benefit of a non-toxic, non-destructive and almost noninvasive
method for sample imaging. CARS can easily be combined with fluorescence confocal
microscopy so it is an excellent complementary imaging method. In this article we
showed some of the applications for this technology: imaging of lipid droplets
inside human HaCaT cells and analysis of the composition of cosmetic products.
Moreover we believe, that soon new fields of application become accessible for
this rapidly developing branch of microscopy.
PMID- 28409575
TI - [Modern methods in analysis of microtubules dynamic in vivo].
AB - Microtubules are involved in any vital cellular activities, including the
maintenance of cell shape, division, migration and intracellular transport.
Microtubule dynamics is regulated by the balance between their polymerization and
depolymerization. Microtubule stability is dependent on their alpha and beta
subunits composition, tubulin post-translational modifications and interaction of
microtubules with microtubule-associated proteins (MAPs). Disruption of these
processes can lead to a number of pathological conditions such as cancer,
cardiovascular disease, or the fibrosis development. This review summarizes the
current knowledge of the modern methods of microtubule polymerization analysis.
This allows a better understanding of the structure and mechanisms played by
microtubules in their physiological functions and the development of pathological
conditions resulting from their disorder.
PMID- 28409576
TI - [Radar as imaging tool in ecology and conservation biology].
AB - Migrations and dispersal are among the most important ecological processes that
shape ecosystems and influence our economy, health and safety. Movements of
birds, bats and insects occur in a large spatial scale - regional, continental,
or intercontinental. However, studies of these phenomena using classic methods
are usually local. Breakthrough came with the development of radar technology,
which enabled researchers to study animal movements in the atmosphere in a large
spatial and temporal scale. The aim of this article was to present the radar
imaging methods used in the research of aerial movements of birds, bats and
insects. The types of radars used in research are described, and examples of the
use of radar in basic research and in conservation biology are discussed. Radar
visualizations are used in studies on the effect of meteorological conditions on
bird migration, on spatial and temporal dynamics of movements of birds, bats and
insects, and on the mechanism of orientation of migrating birds and insects. In
conservation biology research radars are used in the monitoring of endangered
species of birds and bats, to monitor bird activity at airports, as well as in
assessing the impact of high constructions on flying birds and bats.
PMID- 28409577
TI - [Stereo microscope, neglected tool].
AB - Stereoscopes, in author opinion, are neglected tools in modern biology. This
article shortly describes technical and application capabilities of the present
stereomicroscopes. The two main types of stereomicroscope construction are
depicted: Greenough microscope and Common Main Objective microscope. The
technological breakthrough, asymmetrical optical design of stereomicroscopes, the
Fusion Optics, is presented too. Because of very wide offer of a stereomicroscope
platforms, illumination systems, software and imaging systems, the article
contains also very useful factors to consider when selecting a stereomicroscope.
PMID- 28409578
TI - Surgical approach to primitive melanoma.
PMID- 28409579
TI - Recalcitrant cases of pyoderma gangrenosum, responding dramatically to systemic
tacrolimus.
AB - Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous disease, without
any well-known specific and effective treatment. Here we report two patients with
severe recalcitrant perineal pyoderma gangrenosum, successfully treated with low
dose systemic tacrolimus. Tacrolimus can be a safe effective drug in the
management of recalcitrant PG.
PMID- 28409580
TI - Acquired progressive hyperpigmentation.
PMID- 28409581
TI - Therapy of cutaneous larva migrans in pregnancy.
PMID- 28409582
TI - Natural weight-loss products and acne induction in a patient with thyroid
dysfunction.
PMID- 28409584
TI - Atypical syphilitic chancre of the tongue in a HIV-positive patient: the
diagnostic role of NAATS.
PMID- 28409583
TI - Long-term follow-up assessment of daylight photodynamic therapy with methyl
aminolevulinate in patients with actinic keratosis.
PMID- 28409585
TI - Hereditary punctate keratoderma: clinical, pathology, treatment and follow-up.
PMID- 28409586
TI - Dissecting cellulitis: responding to topical steroid and oral clindamycin.
PMID- 28409587
TI - Management of Chronic Pain and Opioid Misuse: A Position Paper from the AAFP.
PMID- 28409588
TI - Chronic Pain Management and Opioid Misuse: Guidance for Family Physicians.
PMID- 28409589
TI - If You Give Amoxicillin/Clavulanate to Six- to 23-Month-Olds with AOM, 10 Days Is
Preferable to Five days.
PMID- 28409591
TI - Placebo Plus Message of Benefit Decreases Chronic Low Back Pain.
PMID- 28409592
TI - Repeat Cytology Within Six Months Equals Colposcopy for Younger Women with ASCUS
or LSIL.
PMID- 28409590
TI - Alzheimer Disease: Monotherapy vs. Combination Therapy.
PMID- 28409594
TI - Correction.
PMID- 28409593
TI - Chronic Obstructive Pulmonary Disease: Diagnosis and Management.
AB - The diagnosis of chronic obstructive pulmonary disease (COPD) should be suspected
in patients with risk factors (primarily a history of smoking) who report dyspnea
at rest or with exertion, chronic cough with or without sputum production, or a
history of wheezing. COPD may be suspected based on findings from the history and
physical examination, but must be confirmed by spirometry to detect airflow
obstruction. Findings that are most helpful to rule in COPD include a smoking
history of more than 40 pack-years, a self-reported history of COPD, maximal
laryngeal height, and age older than 45 years. The combination of three clinical
variables-peak flow rate less than 350 L per minute, diminished breath sounds,
and a smoking history of 30 pack-years or more-is another good clinical
predictor, whereas the absence of all three of these signs essentially rules out
airflow obstruction. Pharmacotherapy and smoking cessation are the mainstays of
treatment, and pulmonary rehabilitation, long-term oxygen therapy, and surgery
may be considered in select patients. Current guidelines recommend starting
monotherapy with an inhaled bronchodilator, stepping up to combination therapy as
needed, and/or adding inhaled corticosteroids as symptom severity and airflow
obstruction progress.
PMID- 28409595
TI - Exercise Prescriptions in Older Adults.
AB - Regular physical activity and exercise are important for healthy aging and are
beneficial for chronic disease management. Exercise prescriptions for older
adults should account for the individual's health status and functional capacity.
Any amount of exercise is better than being sedentary, even if health status
prevents a person from achieving recommended goals. For most health outcomes,
more benefits occur with physical activity performed at higher intensity, greater
frequency, or longer duration. Guidelines recommend at least 150 minutes of
moderate-intensity aerobic activity or 75 minutes of vigorous-intensity aerobic
activity and at least two days of muscle-strengthening activities per week. Key
components of the prescription include setting achievable activity goals,
identifying barriers and providing potential solutions, and providing specific
recommendations on the type, frequency, and intensity of activities. Older adults
will derive distinct benefits from aerobic exercise, strength or resistance
training, flexibility or stretching exercises, and balance training. Many
community resources are available to help older adults begin a more active
lifestyle.
PMID- 28409596
TI - Invisible Disabilities: Mine and Theirs.
PMID- 28409597
TI - PCI Has More Benefits and Harms Than CABG for Selected Patients with Left Main
Coronary Artery Disease.
PMID- 28409599
TI - Pruritic Rash in Pregnancy.
PMID- 28409600
TI - Postpartum Hemorrhage: Prevention and Treatment.
AB - Postpartum hemorrhage is common and can occur in patients without risk factors
for hemorrhage. Active management of the third stage of labor should be used
routinely to reduce its incidence. Use of oxytocin after delivery of the anterior
shoulder is the most important and effective component of this practice. Oxytocin
is more effective than misoprostol for prevention and treatment of uterine atony
and has fewer adverse effects. Routine episiotomy should be avoided to decrease
blood loss and the risk of anal laceration. Appropriate management of postpartum
hemorrhage requires prompt diagnosis and treatment. The Four T's mnemonic can be
used to identify and address the four most common causes of postpartum hemorrhage
(uterine atony [Tone]; laceration, hematoma, inversion, rupture [Trauma];
retained tissue or invasive placenta [Tissue]; and coagulopathy [Thrombin]).
Rapid team-based care minimizes morbidity and mortality associated with
postpartum hemorrhage, regardless of cause. Massive transfusion protocols allow
for rapid and appropriate response to hemorrhages exceeding 1,500 mL of blood
loss. The National Partnership for Maternal Safety has developed an obstetric
hemorrhage consensus bundle of 13 patient- and systems-level recommendations to
reduce morbidity and mortality from postpartum hemorrhage.
PMID- 28409601
TI - Preventing Unintended Adolescent Pregnancy.
PMID- 28409602
TI - Effects of Altered Dietary Salt Intake in Patients with Chronic Kidney Disease.
PMID- 28409603
TI - Vitamin E in Pregnancy.
PMID- 28409604
TI - Interpreting the Statistics on Potential Benefits of Prostate Cancer Screening.
PMID- 28409605
TI - Importance of Careful Corneal Inspection Prior to Fluorescein Exam.
PMID- 28409606
TI - Conversations About Vaccines Should Underscore Their Public Health Benefits to
Patients.
PMID- 28409608
TI - Fever in Well-Appearing Children Younger Than Two Years: A Clinical Policy from
the ACEP.
PMID- 28409607
TI - What Seniors Should Know About Exercise.
PMID- 28409609
TI - Albiglutide (Tanzeum) for Diabetes Mellitus.
PMID- 28409610
TI - Primary Care Interventions to Support Breastfeeding: Recommendation Statement.
PMID- 28409611
TI - Primary Interventions to Support Breastfeeding.
PMID- 28409612
TI - Iron Deficiency in Heart Failure.
PMID- 28409614
TI - Acquired Nail Disorder in an Older Person.
PMID- 28409615
TI - Peritonsillar Abscess.
AB - Peritonsillar abscess is the most common deep infection of the head and neck,
occurring primarily in young adults. Diagnosis is usually made on the basis of
clinical presentation and examination. Symptoms and findings generally include
fever, sore throat, dysphagia, trismus, and a "hot potato" voice. Drainage of the
abscess, antibiotic therapy, and supportive therapy for maintaining hydration and
pain control are the cornerstones of treatment. Most patients can be managed in
the outpatient setting. Peritonsillar abscesses are polymicrobial infections, and
antibiotics effective against group A streptococcus and oral anaerobes should be
first-line therapy. Corticosteroids may be helpful in reducing symptoms and
speeding recovery. Promptly recognizing the infection and initiating therapy are
important to avoid potentially serious complications, such as airway obstruction,
aspiration, or extension of infection into deep neck tissues. Patients with
peritonsillar abscess are usually first encountered in the primary care
outpatient setting or in the emergency department. Family physicians with
appropriate training and experience can diagnose and treat most patients with
peritonsillar abscess.
PMID- 28409616
TI - Severe Asymptomatic Hypertension: Evaluation and Treatment.
AB - Hypertension affects one-third of Americans and is a significant modifiable risk
factor for cardiovascular disease, stroke, renal disease, and death. Severe
asymptomatic hypertension is defined as severely elevated blood pressure (180 mm
Hg or more systolic, or 110 mm Hg or more diastolic) without symptoms of acute
target organ injury. The short-term risks of acute target organ injury and major
adverse cardiovascular events are low in this population, whereas hypertensive
emergencies manifest as acute target organ injury requiring immediate
hospitalization. Individuals with severe asymptomatic hypertension often have
preexisting poorly controlled hypertension and usually can be managed in the
outpatient setting. Immediate diagnostic testing rarely alters short-term
management, and blood pressure control is best achieved with initiation or
adjustment of antihypertensive therapy. Aggressive lowering of blood pressure
should be avoided, and the use of parenteral medications is not indicated.
Current recommendations are to gradually reduce blood pressure over several days
to weeks. Patients with escalating blood pressure, manifestation of acute target
organ injury, or lack of compliance with treatment should be considered for
hospital admission.
PMID- 28409617
TI - Preventing Sports Injury and Illness: Key Resources for Family Physicians.
PMID- 28409618
TI - Zika Virus: Common Questions and Answers.
AB - Since local mosquito-borne transmission of Zika virus was first reported in
Brazil in early 2015, the virus has spread rapidly, with active transmission
reported in at least 61 countries and territories worldwide, including the United
States. Zika virus infection during pregnancy is a cause of microcephaly and
other severe brain anomalies. The virus is transmitted primarily through the bite
of an infected Aedes mosquito, but other routes of transmission include sexual,
mother-to-fetus during pregnancy, mother-to-infant at delivery, laboratory
exposure, and, possibly, transfusion of blood products. Most persons with Zika
virus infection are asymptomatic or have only mild symptoms; hospitalizations and
deaths are rare. When symptoms are present, maculopapular rash, fever,
arthralgia, and conjunctivitis are most common. Zika virus testing is recommended
for persons with possible exposure (those who have traveled to or live in an area
with active transmission, or persons who had sex without a condom with a person
with possible exposure) if they have symptoms consistent with Zika virus disease.
Testing is also recommended for pregnant women with possible exposure, regardless
of whether symptoms are present. Treatment is supportive, and no vaccine is
currently available. The primary methods of prevention include avoiding bites of
infected Aedes mosquitoes and reducing the risk of sexual transmission. Pregnant
women should not travel to areas with active Zika virus transmission, and men and
women who are planning to conceive in the near future should consider avoiding
nonessential travel to these areas. Condoms can reduce the risk of sexual
transmission.
PMID- 28409619
TI - Peritonsillar Abscess: What You Should Know.
PMID- 28409620
TI - Surface Atomic Structure Directs the Fate of Human Mesenchymal Stem Cells.
AB - Stem cells in contact with materials are able to sense their surface features,
integrate extracellular matrix (ECM) protein cues through a signal transduction
pathway, and ultimately direct cell fate decisions. However, discovering the
interdisciplinary mechanisms of how stem cells respond to inherent material
surface features still remains a challenge due to the complex, multicomponent
signaling milieu present in the ECM environment. Here, we demonstrate that the
fate of human mesenchymal stem cells (hMSCs) can be regulated by the inherent
physical cue of the material surface down to atomic-scale features. hMSCs on a
TiO-terminated SrTiO3 {110} substrate tend to differentiate into specific lineage
cells (osteoblast, chondrocyte, adipocyte), whereas on a TiO2-terminated SrTiO3
{100} substrate they are prone to maintain pluripotency. The experimental
observations and molecular dynamics simulations indicate that the distinct
conformations of the initially adsorbed serum albumin and fibronectin proteins
activate the integrin-focal adhesion cytoskeleton actin transduction pathway and,
subsequently, direct the gene and protein expressions of hMSCs. Moreover, we
demonstrate that the initial protein adsorption behaviors are dependent on the
distinct hydroxyl groups originating from different surface atomic structures as
well as the work functions. This work, therefore, provides new insights into the
fundamental understanding of cell-material interactions and will have a profound
impact on further designing materials to direct the stem cell fate.
PMID- 28409621
TI - Ratiometric Singlet Oxygen Detection in Water Using Acene-Doped Conjugated
Polymer Nanoparticles.
AB - Although fluorescent probes for the detection of singlet oxygen (1O2) have been
an active area of research, most such probes rely upon change in intensity of a
single band. Herein, we report a FRET-based, 1O2-sensitive aqueous suspension of
conjugated polymer nanoparticles (CPNs) comprising the energy-donating host
polymer poly[{9,9-dioctyl-2,7-divinylene-fluorenylene}-alt-co-{2-methoxy-5-(2
ethylhexyloxy)-1,4-phenylene}] doped with an energy acceptor, the 1O2-sensitive
thienoacene 5,12-bis(4-methoxyphenyl)-2-butyltetraceno[2,3-b]thiophene. Using a
phthalocyanine-based sensitizer, IRDye 700DX, our probe shows a rapid,
ratiometric response to photosensitized 1O2 in water in both cuvettes and 96-well
plates that compares favorably to the commercial 1O2-sensitive dye, singlet
oxygen sensor green. The response to irradiation of even nanomolar concentrations
of photosensitizer demonstrates the sensitivity of our ratiometric probe.
PMID- 28409623
TI - A Combined Density Functional Theory and Spectrophotometry Study of the Bonding
Interactions of [NpO2.M]4+ Cation-Cation Complexes.
AB - The equilibrium constants for [NpO2.M]4+ (M = Al3+, In3+, Sc3+, Fe3+) in MU = 10
M nitric acid and [NpO2.Ga]4+ in MU = 10 M hydrochloric acid media have been
determined. The trend in the interaction strength follows: Fe3+ > Sc3+ >= In3+ >
Ga3+ ? Al3+. These equilibrium constants are compared to those of previously
reported values for NpO2+ complexes with Cr3+ and Rh3+ within the literature.
Thermodynamic parameters and bonding modes are discussed, with density functional
theory and natural bond orbital analysis indicating that the NpO2+ dioxocation
acts as a pi-donor with transition-metal cations and a sigma-donor with group 13
cations. The small changes in electron-donating ability is modulated by the
overlap with the coordinating metal ion's valence atomic orbitals.
PMID- 28409622
TI - The Activation of Protein Kinase A by the Calcium-Binding Protein S100A1 Is
Independent of Cyclic AMP.
AB - Biochemical and structural studies demonstrate that S100A1 is involved in a Ca2+
dependent interaction with the type 2alpha and type 2beta regulatory subunits of
protein kinase A (PKA) (RIIalpha and RIIbeta) to activate holo-PKA. The
interaction was specific for S100A1 because other calcium-binding proteins (i.e.,
S100B and calmodulin) had no effect. Likewise, a role for S100A1 in PKA-dependent
signaling was established because the PKA-dependent subcellular redistribution of
HDAC4 was abolished in cells derived from S100A1 knockout mice. Thus, the Ca2+
dependent interaction between S100A1 and the type 2 regulatory subunits
represents a novel mechanism that provides a link between Ca2+ and PKA signaling,
which is important for the regulation of gene expression in skeletal muscle via
HDAC4 cytosolic-nuclear trafficking.
PMID- 28409624
TI - Rapid Surface Functionalization of Hydrogen-Terminated Silicon by Alkyl Silanols.
AB - Surface functionalization of inorganic semiconductor substrates, particularly
silicon, has focused attention toward many technologically important
applications, involving photovoltaic energy, biosensing and catalysis. For such
modification processes, oxide-free (H-terminated) silicon surfaces are highly
required, and different chemical approaches have been described in the past
decades. However, their reactivity is often poor, requiring long reaction times
(2-18 h) or the use of UV light (10-30 min). Here, we report a simple and rapid
surface functionalization for H-terminated Si(111) surfaces using alkyl silanols.
This catalyst-free surface reaction is fast (15 min at room temperature) and can
be accelerated with UV light irradiation, reducing the reaction time to 1-2 min.
This grafting procedure leads to densely packed organic monolayers that are
hydrolytically stable (even up to 30 days at pH 3 or 11) and can display
excellent antifouling behavior against a range of organic polymers.
PMID- 28409625
TI - Privileged Structural Motif Detection and Analysis Using Generative Topographic
Maps.
AB - Identification of "privileged structural motifs" associated with specific target
families is of particular importance for designing novel bioactive compounds.
Here, we demonstrate that they can be extracted from a data distribution
represented on a two-dimensional map obtained by Generative Topographic Mapping
(GTM). In GTM, structurally related molecules are grouped together on the map.
Zones of the map preferentially populated by target-specific compounds were
delineated, which helped to capture common substructures on the basis of which
these compounds were grouped together by GTM. Such privileged structural motifs
were identified across three major target superfamilies including proteases,
kinases, and G protein coupled receptors. Traditionally, the search for
privileged structural motifs focused on scaffolds, whereas motifs were detected
here without prior knowledge of compound classification in GTMs. This alternative
way of navigating medicinal chemistry space further extends the classical,
scaffold-centric approach. Importantly, detected motifs might also comprise fuzzy
sets of similar scaffolds, pharmacophore-like patterns, or, by contrast, well
defined scaffolds with specific substituent patterns.
PMID- 28409626
TI - Structural and Electronic Noninnocence of alpha-Diimine Ligands on Niobium for
Reductive C-Cl Bond Activation and Catalytic Radical Addition Reactions.
AB - A d0 niobium(V) complex, NbCl3(alpha-diimine) (1a), supported by a dianionic
redox-active N,N'-bis(2,6-diisopropylphenyl)-1,4-diaza-2,3-dimethyl-1,3-butadiene
(alpha-diimine) ligand (ene-diamido ligand) served as a catalyst for radical
addition reactions of CCl4 to alpha-olefins and cyclic alkenes, selectively
affording 1:1 radical addition products in a regioselective manner. During the
catalytic reaction, the alpha-diimine ligand smoothly released and stored an
electron to control the oxidation state of the niobium center by changing between
an eta4-(sigma2,pi) coordination mode with a folded MN2C2 metallacycle and a
kappa2-(N,N') coordination mode with a planar MN2C2 metallacycle. Kinetic studies
of the catalytic reaction elucidated the reaction order in the catalytic cycle:
the radical addition reaction rate obeyed first-order kinetics that were
dependent on the concentrations of the catalyst, styrene, and CCl4, while a
saturation effect was observed at a high CCl4 concentration. In the presence of
excess amounts of styrene, styrene coordinated in an eta2-olefinic manner to the
niobium center to decrease the reaction rate. No observation of oligomers or
polymers of styrene and high stereoselectivity for the radical addition reaction
of CCl4 to cyclopentene suggested that the C-C bond formation proceeded inside
the coordination sphere of niobium, which was in good accordance with the
negative entropy value of the radical addition reaction. Furthermore, reaction of
1a with (bromomethyl)cyclopropane confirmed that both the C-Br bond activation
and formation proceeded on the alpha-diimine-coordinated niobium center during
transformation of the cyclopropylmethyl radical to a homoallyl radical. With
regard to the reaction mechanism, we detected and isolated NbCl4(alpha-diimine)
(6a) as a transient one-electron oxidized species of 1a during reductive cleavage
of the C-X bonds; in addition, the monoanionic alpha-diimine ligand of 6a adopted
a monoanionic canonical form with selective one-electron oxidation of the
dianionic ene-diamido form of the ligand in 1a.
PMID- 28409627
TI - Simultaneous ATR-FTIR Based Determination of Malaria Parasitemia, Glucose and
Urea in Whole Blood Dried onto a Glass Slide.
AB - New diagnostic tools that can detect malaria parasites in conjunction with other
diagnostic parameters are urgently required. In this study, Attenuated Total
Reflection Fourier transform infrared (ATR-FTIR) spectroscopy in combination with
Partial Least Square Discriminant Analysis (PLS-DA) and Partial Least Square
Regression (PLS-R) have been applied as a point-of-care test for identifying
malaria parasites, blood glucose, and urea levels in whole blood samples from
thick blood films on glass slides. The specificity for the PLS-DA was found to be
98% for parasitemia levels >0.5%, but a rather low sensitivity of 70% was
achieved because of the small number of negative samples in the model. In PLS-R
the Root Mean Square Error of Cross Validation (RMSECV) for parasite
concentration (0-5%) was 0.58%. Similarly, for glucose (0-400 mg/dL) and urea (0
250 mg/dL) spiked samples, relative RMSECVs were 16% and 17%, respectively. The
method reported here is the first example of multianalyte/disease diagnosis using
ATR-FTIR spectroscopy, which in this case, enabled the simultaneous
quantification of glucose and urea analytes along with malaria parasitemia
quantification using one spectrum obtained from a single drop of blood on a glass
microscope slide.
PMID- 28409628
TI - Reversion of P-gp-Mediated Drug Resistance in Ovarian Carcinoma Cells with PHPMA
Zosuquidar Conjugates.
AB - Inhibition of P-glycoprotein (P-gp) transporter is an attractive approach for the
reversion of cancer-associated multidrug resistance (MDR). Poly(N-(2
hydroxypropyl) methacrylamide) (PHPMA)-based carriers that are able to release
the anticancer drug doxorubicin in the lysosomes have shown promise to reduce P
gp mediated resistance. This is attributed to the release of the drug in close
proximity to the nucleus and distant from the P-gp transporter. This work
presents a strategy to maximize P-gp inhibition and enhance doxorubicin
cytotoxicity in cancer cells by using a dual functional PHPMA conjugate carrying
both the anticancer drug doxorubicin and the P-glycoprotein inhibitor zosuquidar
(Zos). While doxorubicin was connected to the polymer backbone via a lysosomally
cleavable spacer, the P-gp inhibitor Zos was attached by a hydrazone linker in
order to promote release in the early stage of the endocytic process and maximize
its cytosolic concentration in proximity of the P-gp transporter. Following Zos
modification and determination of its ability to inhibit P-gp, conjugation to the
PHPMA polymer backbone resulted in enhanced doxorubicin cytotoxicity in resistant
A2780ADR ovarian carcinoma cells. Finally, the incorporation of both Dox and Zos
in a single polymer carrier enhanced P-gp inhibition as compared to a control
PHPMA conjugate containing only Dox.
PMID- 28409629
TI - Tuning the Extent and Depth of Penetration of Flexible Liposomes in Human Skin.
AB - In this work we made an attempt to assess the effect of drug-induced changes of
flexibility on the penetration of deformable vesicles into the human skin. Eight
cationic liposomes with different degrees of flexibility were obtained by
entrapping unfractionated heparin, enoxaparin, and nadroparin. The deformability
was studied by a novel, facile, and reliable extrusion assay appositely developed
and validated by means of quantitative nanoscale mechanical AFM measurements of
vesicle elastic modulus (log10(YM)). The proposed extrusion assay, determining
the forces involved in vesicles deformation, resulted very sensitive to evidence
of minimal changes in bilayer rigidity (sigma) and vesicle deformation (K). The
drug loading caused a reduction of liposome flexibility with respect to the
reference plain liposomes and in accordance to the heparin type, drug to cationic
lipid (DOTAP) ratio, and drug distribution within the vesicles. Interestingly,
the sigma and log10(YM) values perfectly correlated (R2 = 0.935), demonstrating
the reliability of the deformability data obtained with both approaches. The
combination of TEM and LC-MS/MS spectrometry allowed the pattern of the
penetration of the entire vesicles into the skin to be followed. In all cases,
intact liposomes in the epidermis layers were observed and a relationship between
the depth of penetration and the liposome flexibility was found, supporting the
hypothesis of the whole vesicle penetration mechanism. Moreover, the results of
the extent (R24) of vesicle penetration in the human skin samples showed a direct
relation to the flexibility values (sigma1 = 0.65 +/- 0.10 MPa -> R24 = 3.33 +/-
0.02 MUg/mg; sigma2 = 0.95 +/- 0.04 MPa -> R24 = 1.18 +/- 0.26 MUg/mg; sigma3 =
1.89 +/- 0.30 MPa -> R24 = 0.53 +/- 0.33 MUg/mg).
PMID- 28409630
TI - Silver(I)-Catalyzed Regioselective Synthesis of Triazole Fused-1,5
Benzoxazocinones.
AB - An efficient and regioselective synthesis of novel 1,2,3-triazole-fused-1,5
benzoxazocinones through intramolecular cyclization of substituted ethynyl
triazoyl benzoic acids was explored. A crucial precursor 5-iodo-1,2,3-triazole
benzoate was obtained from substituted 2-azido benzoic acid esters in a single
step through a Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction using
a CuI/NBS catalytic system. A carbon-carbon triple bond was installed through a
Sonogashira coupling reaction by various terminal alkynes. Finally, the 1,4,5
substituted ethynyl triazoyl benzoic acids were cyclized by a AgOTf-mediated
intramolecular cyclization to afford 8-endo-dig 1,2,3-triazole-fused-1,5
benzoxazocinones exclusively.
PMID- 28409631
TI - Entropy-Driven Ball-in-Bowl Assembly of Fullerene and Geodesic Phenylene Bowl.
AB - Complexation of C60 at a conical region of a nanometer-sized geodesic phenylene
bowl has been demonstrated. Proton NMR spectroscopy showed formation of a 1:1
complex that was driven by entropy gains for the assembly. Crystallographic
analyses revealed its unique ball-in-bowl structure, and the presence of smoothly
curved surfaces was unveiled at their interfaces.
PMID- 28409632
TI - Resonant Nonplasmonic Nanoparticles for Efficient Temperature-Feedback Optical
Heating.
AB - We propose a novel photothermal approach based on resonant dielectric
nanoparticles, which possess imaginary part of permittivity significantly smaller
as compared to metal ones. We show both experimentally and theoretically that a
spherical silicon nanoparticle with a magnetic quadrupolar Mie resonance converts
light to heat up to 4 times more effectively than similar spherical gold
nanoparticle at the same heating conditions. We observe photoinduced temperature
raise up to 900 K with the silicon nanoparticle on a glass substrate at moderate
intensities (<2 mW/MUm2) and typical laser wavelength (633 nm). The advantage of
using crystalline silicon is the simplicity of local temperature control by means
of Raman spectroscopy working in a broad range of temperatures, that is, up to
the melting point of silicon (1690 K) with submicrometer spatial resolution. Our
CMOS-compatible heater-thermometer nanoplatform paves the way to novel
nonplasmonic photothermal applications, extending the temperature range and
simplifying the thermoimaging procedure.
PMID- 28409633
TI - Tunable Nitric Oxide Release from S-Nitroso-N-acetylpenicillamine via Catalytic
Copper Nanoparticles for Biomedical Applications.
AB - The quest for novel therapies to prevent bacterial infections and blood clots
(thrombosis) is of utmost importance in biomedical research due to the
exponential growth in the cases of thrombosis and blood infections and the
emergence of multi-drug-resistant strains of bacteria. Endogenous nitric oxide
(NO) is a cellular signaling molecule that plays a pivotal role in host immunity
against pathogens, prevention of clotting, and regulation of systemic blood
pressure, among several other biological functions. The physiological effect of
NO is dose dependent, which necessitates the study of its tunable release
kinetics, which is the objective of this study. In the present study, polymer
composites were fabricated by incorporating S-nitroso-N-acetylpenicillamine
(SNAP) in a medical-grade polymer, Carbosil, and top-coated with varying
concentrations of catalytic copper nanoparticles (Cu-NPs). The addition of the Cu
NPs increased the NO release, as well as the overall antimicrobial activity via
the oligodynamic effect of Cu. SNAP (10 wt %) composites without Cu-NP coatings
showed a NO flux of 1.32 +/- 0.6 * 10-10 mol min-1 cm-2, whereas Cu-NP
incorporated SNAP films exhibited fluxes of 4.48 +/- 0.5 * 10-10, 4.84 +/- 0.3 *
10-10, and 11.7 +/- 3.6 * 10-10 mol min-1 cm-2 with 1, 3, and 5 wt % Cu-NPs,
respectively. This resulted in a significant reduction (up to 99.8%) in both gram
positive and gram-negative bacteria, with very low platelet adhesion (up to 92%
lower) as compared to that of the corresponding controls. Copper leachates from
the SNAP films were detected using the inductively coupled plasma-mass
spectrometry technique and were found to be significantly lower in concentration
than the recommended safety limit by the FDA. The cell viability test performed
on mouse fibroblast 3T3 cells provided supportive evidence for the
biocompatibility of the material in vitro.
PMID- 28409634
TI - Calcium, Ammonia, Redox-Active Tyrosine YZ, and Proton-Coupled Electron Transfer
in the Photosynthetic Oxygen-Evolving Complex.
AB - A redox-active tyrosine, YZ (Y161 in the D1 polypeptide), is essential in
photosystem II (PSII), which conducts photosynthetic oxygen evolution. On each
step of the light-driven oxygen evolving reaction, YZ radical is formed by a
chlorophyll cation radical. YZ radical is then reduced by a Mn4CaO5 cluster in a
proton coupled electron transfer (PCET) reaction. YZ is hydrogen bonded to His190
D1 and to water molecules in a hydrogen-bonding network, involving calcium. This
network is sensitive to disruption with ammonia and to removal and replacement of
calcium. Only strontium supports activity. Here, we use electron paramagnetic
resonance (EPR) spectroscopy to define the influence of ammonia treatment,
calcium removal, and strontium/barium substitution on YZ radical PCET at two pH
values. A defined oxidation state of the metal cluster (S2) was trapped by
illumination at 190 K. The net reduction and protonation of YZ radical via PCET
were monitored by EPR transients collected after a 532 nm laser flash. At 190 K,
YZ radical cannot oxidize the Mn4CaO5 cluster and decays on the seconds time
scale by recombination with QA-. The overall decay half-time and biexponential
fits were used to analyze the results. The reaction rate was independent of pH in
control, calcium-reconstituted PSII (Ca-PSII). At pH 7.5, the YZ radical decay
rate decreased in calcium-depleted (CD-PSII) and barium/strontium-reconstituted
PSII (Ba-PSII, Sr-PSII), relative to Ca-PSII. At pH 6.0, the YZ radical decay
rate was not significantly altered in CD-PSII and Sr-PSII but decreased in Ba
PSII. A two-pathway model, involving two competing proton donors with different
pKa values, is proposed to explain these results. Ammonia treatment decreased the
YZ decay rate in Ca-PSII, Sr-PSII, and CD-PSII, consistent with a reaction that
is mediated by the hydrogen-bonding network. However, ammonia treatment did not
alter the rate in Ba-PSII. This result is interpreted in terms of the large ionic
radius of barium and the elevated pKa of barium-bound water, which are expected
to disrupt hydrogen bonding. In addition, evidence for a functional interaction
between the S2 protonated water cluster (Wn+) and the YZ proton donation pathway
is presented. This interaction is proposed to increase the rate of the YZ PCET
reaction.
PMID- 28409635
TI - Gold(I)-Catalyzed [2 + 2 + 2] Cyclotrimerization of 1,3-Diarylpropargyl Acetals.
AB - A gold-nitrone catalyzed [2 + 2 + 2] cyclotrimerization of 1,3-diarylpropargyl
acetals into cyclohexylidene products (up to 74% yield) is reported. The
trimerization is proposed to proceed through allenic intermediates via gold
catalyzed 1,3-alkoxy rearrangement. The presence of catalytic amounts of
different nitrones, tuning of the Au(I) catalyst activity, was essential for
controlled regio-/chemoselective cyclotrimerization. A linear nitrone-O-Au(I)-P
coordination mode was shown (X-ray analysis) for a catalytic active phosphane
gold-nitrone complex, representing a group of Au(I) catalysts with specific
properties.
PMID- 28409636
TI - Signal-On Photoelectrochemical Immunoassay for Aflatoxin B1 Based on Enzymatic
Product-Etching MnO2 Nanosheets for Dissociation of Carbon Dots.
AB - Aflatoxin B1 (AFB1) monitoring has attracted extensive attention because food
safety is a worldwide public health problem. Herein, we design a novel
simultaneously visual and photoelectrochemical (PEC) immunosensing system for
rapid sensitive detection of AFB1 in foodstuff. The immunoreaction was carried
out on anti-AFB1 antibody-modified magnetic beads by using glucose oxidase (GOx)
labeled AFB1-bovine serum albumin (AFB1-BSA) conjugates as the tags with a
competitive-type immunoassay format, while the visual and PEC evaluation was
performed via carbon quantum dots (CQDs)-functionalized MnO2 nanosheets.
Accompanying the formation of immunocomplexes, the carried GOx initially oxidized
the substrate (glucose) for the generation of H2O2, which reduced/etched MnO2
nanosheets into Mn2+ ions, thereby resulting in the dissociation of CQDs from the
electrode. Within the applied potentials, the photocurrent of MnO2-CQDs-modified
electrode decreased with the increasing H2O2 level in the detection cell.
Meanwhile, a visual detection could be performed according to the change in the
color of MnO2-CQDs-coated electrode. To elaborate, this system was aggregated
into a high-throughput microfluidic device to construct a semiautomatic detection
cell. Under optimal conditions, the photocurrent increased with the increasing
target AFB1 within a dynamic working range from 0.01 to 20 ng mL-1 with a limit
of detection (LOD) of 2.1 pg mL-1 (ppt). The developed immunoassay exhibited good
reproducibility and acceptable accuracy. In addition, the method accuracy
relative to AFB1 ELISA kit was evaluated for analyzing naturally contaminated or
spiked peanut samples, giving the well-matched results between two methods.
Although our strategy was focused on the detection of target AFB1, it is easily
extended to screen other small molecules or mycotoxins, thereby representing a
versatile immunosensing scheme.
PMID- 28409637
TI - Halogenated Compounds from Directed Fermentation of Penicillium concentricum, an
Endophytic Fungus of the Liverwort Trichocolea tomentella.
AB - One new chlorinated xanthone, 6-chloro-3,8-dihydroxy-1-methylxanthone (1), a new
2-bromo-gentisyl alcohol (2), and a mixture of 6-epimers of 6-dehydroxy-6
bromogabosine C (3a and 3b), together with 19 previously identified compounds,
epoxydon (4), norlichexanthone (5), 2-chlorogentisyl alcohol (6),
hydroxychlorogentisyl quinone (7), 6-dehydroxy-6alpha-chlorogabosine C (8a), 6
dehydroxy-6beta-chlorogabosine C (8b), gentisyl alcohol (9), gentisyl quinone
(10), (R,S)-1-phenyl-1,2-ethanediol (11), dehydrodechlorogriseofulvin (12),
dechlorogriseofulvin (13), dehydrogriseofulvin (14), griseofulvin (15), ethylene
glycol benzoate (16), alternariol (17), griseoxanthone C (18), drimiopsin H (19),
griseophenone C (20), and griseophenone B (21), were isolated from cultures of
Penicillium concentricum, a fungal endophyte of the liverwort Trichocolea
tomentella. The structures of the new compounds (1, 2, 3a, and 3b) were
elucidated by interpretation of spectroscopic data including one- and two
dimensional NMR techniques. Among these, compounds 2-4 displayed modest
cytotoxicity to the MCF-7 hormone-dependent breast cancer cell line with IC50
values of 8.4, 9.7, and 5.7 MUM, respectively, whereas compound 9 exhibited
selective cytotoxicity against the HT-29 colon cancer cell line with an IC50
value of 6.4 MUM. During this study we confirmed that the brominated gentisyl
alcohol (2) was formed by chemical conversion of 4 during bromide salt addition
to culture media.
PMID- 28409638
TI - A Flexible Solid Composite Electrolyte with Vertically Aligned and Connected Ion
Conducting Nanoparticles for Lithium Batteries.
AB - Replacing flammable organic liquid electrolytes with solid Li-ion conductors is a
promising approach to realize safe rechargeable batteries with high energy
density. Composite solid electrolytes, which are comprised of a polymer matrix
with ceramic Li-ion conductors dispersed inside, are attractive, since they
combine the flexibility of polymer electrolytes and high ionic conductivities of
ceramic electrolytes. However, the high conductivity of ceramic fillers is
largely compromised by the low conductivity of the matrix, especially when
nanoparticles (NPs) are used. Therefore, optimizations of the geometry of ceramic
fillers are critical to further enhance the conductivity of composite
electrolytes. Here we report the vertically aligned and connected Li1+xAlxTi2
x(PO4)3 (LATP) NPs in the poly(ethylene oxide) (PEO) matrix to maximize the ionic
conduction, while maintaining the flexibility of the composite. This vertically
aligned structure can be fabricated by an ice-templating-based method, and its
conductivity reaches 0.52 * 10-4 S/cm, which is 3.6 times that of the composite
electrolyte with randomly dispersed LATP NPs. The composite electrolyte also
shows enhanced thermal and electrochemical stability compared to the pure PEO
electrolyte. This method opens a new approach to optimize ion conduction in
composite solid electrolytes for next-generation rechargeable batteries.
PMID- 28409639
TI - Design, Synthesis, and Biological Evaluation of Dimorpholine Substituted
Thienopyrimidines as Potential Class I PI3K/mTOR Dual Inhibitors.
AB - Dysfunctional signaling of the PI3K/AKT/mTOR pathway in cancer and its crucial
role in cell growth and survival have made it a much desired target for cancer
therapeutics. A series of dimorpholine substituted thienopyrimidine derivatives
had been prepared and evaluated in vitro and in vivo. Among them, compound 14o
was identified as a dual Class I PI3K and mTOR kinase inhibitor, which had an
approximately 8-fold improvement in mTOR inhibition relative to the class I PI3K
inhibitor 1 (pictilisib, GDC-0941). Western blot analysis confirmed the 14o
mechanistic modulation of the cellular PI3K/AKT/mTOR pathway through inhibiting
phosphorylation of both AKT and S6 in human cancer cell lines. In addition, 14o
demonstrated significant efficacy in SKOV-3 and U87MG tumor xenograft models
without causing significant weight loss and toxicity.
PMID- 28409640
TI - Polymer-Pen Chemical Lift-Off Lithography.
AB - We designed and fabricated large arrays of polymer pens having sub-20 nm tips to
perform chemical lift-off lithography (CLL). As such, we developed a hybrid
patterning strategy called polymer-pen chemical lift-off lithography (PPCLL). We
demonstrated PPCLL patterning using pyramidal and v-shaped polymer-pen arrays.
Associated simulations revealed a nanometer-scale quadratic relationship between
contact line widths of the polymer pens and two other variables: polymer-pen base
line widths and vertical compression distances. We devised a stamp support system
consisting of interspersed arrays of flat-tipped polymer pens that are taller
than all other sharp-tipped polymer pens. These supports partially or fully
offset stamp weights thereby also serving as a leveling system. We investigated a
series of v-shaped polymer pens with known height differences to control relative
vertical positions of each polymer pen precisely at the sub-20 nm scale mimicking
a high-precision scanning stage. In doing so, we obtained linear-array patterns
of alkanethiols with sub-50 nm to sub-500 nm line widths and minimum sub-20 nm
line width tunable increments. The CLL pattern line widths were in agreement with
those predicted by simulations. Our results suggest that through informed design
of a stamp support system and tuning of polymer-pen base widths, throughput can
be increased by eliminating the need for a scanning stage system in PPCLL without
sacrificing precision. To demonstrate functional microarrays patterned by PPCLL,
we inserted probe DNA into PPCLL patterns and observed hybridization by
complementary target sequences.
PMID- 28409641
TI - Efficient Second-Harmonic Generation in Nanocrystalline Silicon Nanoparticles.
AB - Recent trends to employ high-index dielectric particles in nanophotonics are
motivated by their reduced dissipative losses and large resonant enhancement of
nonlinear effects at the nanoscale. Because silicon is a centrosymmetric
material, the studies of nonlinear optical properties of silicon nanoparticles
have been targeting primarily the third-harmonic generation effects. Here we
demonstrate, both experimentally and theoretically, that resonantly excited
nanocrystalline silicon nanoparticles fabricated by an optimized laser printing
technique can exhibit strong second-harmonic generation (SHG) effects. We
attribute an unexpectedly high yield of the nonlinear conversion to a
nanocrystalline structure of nanoparticles supporting the Mie resonances. The
demonstrated efficient SHG at green light from a single silicon nanoparticle is 2
orders of magnitude higher than that from unstructured silicon films. This
efficiency is significantly higher than that of many plasmonic nanostructures and
small silicon nanoparticles in the visible range, and it can be useful for a
design of nonlinear nanoantennas and silicon-based integrated light sources.
PMID- 28409642
TI - Protic Ionic Liquids for the Belousov-Zhabotinsky Reaction: Aspects of the BZ
Reaction in Protic Ionic Liquids and Its Use for the Autonomous Coil-Globule
Oscillation of a Linear Polymer.
AB - Herein, we describe the physicochemical aspects of the Belousov-Zhabotinsky (BZ)
reaction in hydrated protic ionic liquids (PILs) combined with different cations
with a hydrogen sulfate ([HSO4-]) anion. PILs were prepared from the
neutralization reactions of sulfuric acid with 13 different aliphatic amines. The
amine structure was selected to investigate the effect of the number of active
protons, alkyl chain length (hydrophilicity), and cationic linearity on the
mechanism of the BZ reaction. The pKa values of PILs were significantly higher
(pKa = 1.0-2.5) than those of inorganic acids (H2SO4 = -3.0; HNO3 = -1.4), the
conventional proton source in a BZ reaction. A periodic redox oscillation was
observed in Ru(bpy)3 when appropriate amounts of BZ reaction substrates (NaBrO3
oxidant; malonic acid reductant) were added to the hydrated PILs. A long-lasting
BZ oscillation was realized when hydrophilic cations (ammonium, ethylammonium,
and dimethylethylammonium) were employed. Interestingly, a large DeltaA5000
(oscillation amplitude of absorbance for the scale of the oscillation stability
observed after 5000 s from the initiation of the BZ reaction) was achieved for
PILs possessing less than four carbon atoms in their cationic structure. The
apparent BZ oscillation activation energy (Ea) in the hydrated PILs was estimated
to be ~40 kJ mol-1, which is 30 kJ mol-1 less than that observed in a
conventional system. The catalytic reaction in the BZ reaction subprocess
suppresses the total activation energy of the reaction. To realize long-lasting
self-oscillating polymeric materials acting under milder condition, we
demonstrated an autonomous coil-globule polymer chain transition (BZ-driven) that
directly converts chemical energy to mechanical motion in hydrated PILs without
freely diffusing Ru(bpy)3 metal catalyst. Ethylammonium hydrogen sulfate ([ea
H+][HSO4-]) is selected as the suitable proton source for the BZ reaction. A well
defined self-oscillating polymer that incorporated Ru(bpy)3 metal catalyst into
the polymer backbone accompanied by good compatibility in hydrated [ea-H+][HSO4-]
is successfully prepared by ATRP, followed by postmodification of the metal
catalyst. The rhythmic solubility changes of the polymer under milder conditions,
realized by combination with PILs, will expand the potential applications of PILs
to novel functional materials.
PMID- 28409643
TI - Economical Doubly Electron-Attached Equation-of-Motion Coupled-Cluster Methods
with an Active-Space Treatment of Three-Particle-One-Hole and Four-Particle-Two
Hole Excitations.
AB - The previously developed active-space doubly electron-attached (DEA) equation-of
motion (EOM) coupled-cluster (CC) method with up to four-particle-two-hole (4p
2h) excitations [Shen, J.; Piecuch, P. J. Chem. Phys. 2013, 138, 194102], which
utilizes the idea of applying a linear electron-attaching operator to the CC
ground state of an (N - 2)-electron closed-shell system to generate ground and
excited states of the N-electron open-shell species of interest, has been
extended to a considerably less expensive model, in which both 3p-1h and 4p-2h
terms rather than 4p-2h contributions only are selected using active orbitals. As
illustrated by the calculations involving low-lying singlet and triplet states of
methylene, trimethylenemethane, cyclobutadiene, and cyclopentadienyl cation and
bond breaking in F2, the proposed DEA-EOMCC method with the active-space
treatment of 3p-1h and 4p-2h excitations and its lower-level counterpart
neglecting 4p-2h contributions are capable of accurately reproducing the results
obtained using their considerably more expensive parent counterparts with a full
treatment of 3p-1h and full or active-space treatment of 4p-2h excitations.
PMID- 28409644
TI - Amphiphilic Tobramycin-Lysine Conjugates Sensitize Multidrug Resistant Gram
Negative Bacteria to Rifampicin and Minocycline.
AB - Chromosomally encoded low membrane permeability and highly efficient efflux
systems are major mechanisms by which Pseudomonas aeruginosa evades antibiotic
actions. Our previous reports have shown that amphiphilic tobramycin
fluoroquinolone hybrids can enhance efficacy of fluoroquinolone antibiotics
against multidrug-resistant (MDR) P. aeruginosa isolates. Herein, we report on a
novel class of tobramycin-lysine conjugates containing an optimized amphiphilic
tobramycin-C12 tether that sensitize Gram-negative bacteria to legacy
antibiotics. Combination studies indicate the ability of these conjugates to
synergize rifampicin and minocycline against MDR and extensively drug resistant
(XDR) P. aeruginosa isolates and enhance efficacy of both antibiotics in the
Galleria mellonella larvae in vivo infection model. Mode of action studies
indicate that the amphiphilic tobramycin-lysine adjuvants enhance outer membrane
cell penetration and affect the proton motive force, which energizes efflux
pumps. Overall, this study provides a strategy for generating effective
antibiotic adjuvants that overcome resistance of rifampicin and minocycline in
MDR and XDR Gram-negative bacteria including P. aeruginosa.
PMID- 28409645
TI - Evaluation of platelet function in thrombocytopenia.
AB - Whole blood aggregometry is a functional assay for determination of platelet
function. Until now, whole blood aggregometry has not been considered feasible at
low platelet counts. Hence, the objectives of the present study were to explore
platelet function in thrombocytopenia using a novel index of impedance
aggregometry adjusted for platelet count and evaluate the association to platelet
function assessed by flow cytometry. Hirudin anticoagulated blood was collected
from 20 healthy volunteers, 20 patients with primary immune thrombocytopenia
(ITP), and 17 hematological cancer patients. Platelet function was analyzed by
impedance aggregometry and by flow cytometry. Collagen, adenosine diphosphate,
thrombin receptor agonist peptide-6, and ristocetin were used as agonists for
both analyses. Thrombocytopenia in healthy whole blood was induced in vitro
employing a recently published method. Platelet aggregation of thrombocytopenic
patients was evaluated relative to the aggregation of healthy volunteers at the
same platelet count. In flow cytometry, platelet function was described as
expression of the platelet surface glycoproteins: bound fibrinogen, CD63, and P
selectin. Similar platelet counts were obtained in the patient groups (p = 0.69)
(range: 13-129 * 109/l). Aggregation adjusted for platelet count was
significantly increased in ITP patients compared to healthy platelets across all
agonists. The platelet aggregation was high in the 95% prediction interval, with
18 ITP patients above the prediction interval in at least two agonists. In
contrast, the platelet aggregation was low in the prediction interval in cancer
patients, and three cancer patients with platelet aggregation below the
prediction interval in at least one agonist. ITP patients displayed increased
expression of bound fibrinogen and CD63 following activation, compared with
particularly cancer patients, but also compared with healthy platelets. This
study demonstrated the feasibility of a novel approach to perform platelet
function analyses in thrombocytopenia using impedance aggregometry adjusted for
platelet count.
PMID- 28409647
TI - Cultural Attitudes toward Postpartum Depression in Dhaka, Bangladesh.
AB - Depression is the leading cause of disability worldwide, yet in many cultures, it
remains unaddressed and unacknowledged. Postpartum depression is particularly
delicate because of its association with gender and expectations of motherhood.
This ethnographic study in Dhaka, Bangladesh sought to understand local
perceptions of postpartum depression and cultural influences around mental health
care seeking. The results describe the role of culture and stigma in the
conceptualization of mental health within both the community and medical spheres.
Mental health continues to be unacknowledged and neglected in Bangladeshi
communities. We recommend community-based psychosocial programming for new
mothers living in slums.
PMID- 28409646
TI - Intravitreal bevacizumab alters type IV collagenases and exacerbates arrested
alveologenesis in the neonatal rat lungs.
AB - : Purpose/Aim: Intravitreal bevacizumab (Avastin) is an irreversible vascular
endothelial growth factor (VEGF) inhibitor used off-label to treat severe
retinopathy of prematurity in extremely low gestational age neonates. VEGF and
matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases
(TIMPs) participate in lung maturation. We tested the hypothesis that
intravitreal bevacizumab enters the systemic circulation and has long-lasting
effects on lung MMPs. MATERIALS AND METHODS: Neonatal rats were exposed to: (1)
hyperoxia (50% O2); (2) intermittent hypoxia (IH) (50% O2 with brief episodes of
12% O2); or (3) room air (RA) from birth (P0) to P14. At P14, the time of eye
opening in rats, a single dose of Avastin (0.125 mg) was injected into the
vitreous cavity of the left eye. A control group received equivalent volume
saline. At P23 and P45, lung MMP-2 and MMP-9, and TIMP-1, and TIMP-2 were
assessed in the lungs. RESULTS: At P23, Avastin increased MMP-2, MMP-9, and TIMP
1 levels in the hyperoxia group but decreased TIMP-1 levels in the IH group. The
ratios of MMP-2/TIMP-1 and MMP-9/TIMP-1 were significantly elevated at P23 in the
IH group treated with Avastin. At P45, the levels of MMP-2 and MMP-9 remained
elevated in the hyperoxia and IH groups treated with Avastin, while a rebound
increase in TIMP-1 levels was noted in the IH group. CONCLUSIONS: Avastin
treatment in IH has lasting alterations in the balance between MMPs and their
tissue inhibitors. These changes may lead to impaired alveologenesis and tissue
damage consistent with bronchopulmonary dysplasia/chronic lung disease.
PMID- 28409648
TI - Assessment of Simulated Emergency Scenarios: Are Trained Observers Necessary?
AB - OBJECTIVES: Simulation-based medical training is associated with superior
educational outcomes and improved cost efficiency. Self- and peer-assessment may
be a cost-effective and flexible alternative to expert-led assessment. We
compared accuracy of self- and peer-assessment of untrained raters using basic
evaluation tools to expert assessment using advanced validation tools including
validated questionnaires and post hoc video-based analysis. METHODS: Twenty-eight
simulated emergency airway management scenarios were observed and video-recorded
for further assessment. Participants consisted of 28 emergency physicians who
were involved in four different airway management scenarios with different roles:
One scenario as a team leader, one as an assisting team member, and two as an
observer. Non-technical skills (NTS) and technical skills (TS) were analyzed by
three independent groups: 1) the performing team (PT) consisted of the two
emergency physicians acting either in the role of team leader or team member
(self-assessment); 2) the observing team (OT), consisted of two of the
participating emergency physicians not involved in the current clinical scenario
(peer-assessment) and assessment occurred during (OT) or directly after (PT) the
simulation without prior specific interpretational training but using
standardized questionnaires; and 3) the expert team (ET) consisted of two
specifically trained external observers (one psychologist and one emergency
physician) using video-assisted objective assessment combined with standardized
questionnaires. RESULTS: Intragroup reliability demonstrated by intra-class
correlation (ICC) was moderate to good for TS (ICC 0.42*) and NTS (ICC 0.55*) in
PT and moderate to good for TS (ICC 0.41*) or poor for NTS (ICC 0.27) in OT. ET
showed an excellent intragroup reliability for both TS (ICC 0.78*) and NTS (ICC
0.81*). Interrater reliability was significantly different between ET and PT and
between ET and OT for both TS and NTS. There was no difference between OT and PT
for neither TS nor NTS; *p < 0.05. CONCLUSIONS: Expert assessment of simulation
based medical training scenarios using validated checklists and performance of
post hoc video-based analysis was superior to self- or peer-assessment of
untrained observers for both TS and NTS.
PMID- 28409649
TI - Lexical stress contrast marking in fluent and non-fluent aphasia in Spanish: The
relationship between acoustic cues and compensatory strategies.
AB - This study sought to investigate stress production in Spanish by patients with
Broca's (BA) and conduction aphasia (CA) as compared to controls. Our objectives
were to assess whether: a) there were many abnormal acoustic correlates of stress
as produced by patients, b) these abnormalities had a phonetic component and c)
ability for articulatory compensation for stress marking was preserved. The
results showed abnormal acoustic values in both BA and CA's productions,
affecting not only duration but also F0 and intensity cues, and an interaction
effect of stress pattern and duration on intensity cubes in BA, but not in CA or
controls. The results are interpreted as deriving from two different underlying
phenomena: in BA, a compensatory use of intensity as a stress cue in order to
avoid 'equal stress'; in CA, related to either a 'subtle phonetic deficit'
involving abnormal stress acoustic cue-processing or to 'clear-speech' effects.
PMID- 28409650
TI - Stigma and Psychiatric/Mental Health Nursing.
PMID- 28409651
TI - Reliability of Fear Assessment in Growing Pigs Exposed to a Novel Object Test in
Commercial Conditions.
AB - The objective of this study was to assess the reliability and feasibility of a
novel object test assessing fear in pigs in commercial conditions. A total of 18
commercial farms were visited, and 321 pens housing 4,220 growing pigs were
assessed. Three balloons were used as a novel stimulus. Measures were (a) the
time it took for the first pig to contact 1 of the balloons, (b) percentage of
nonhuman animals watching the balloons each for 10 s, and (c) percentage of
animals touching the balloons during periods of 5 s. The time of the first pig to
contact 1 of the balloons ranged from 0 s to 362 s. An effect of the farm was
found (p < .0001) for contact latency, ranging from 6.8 s to 73.3 s, but little
difference was found in terms of intrafarm variability. Interobserver
repeatability was also high in this measure, ranging from r = .74 to r = .96. As
a result, it is concluded that contact latency could be a good measure to assess
fear of a novel stimulus in commercial farms.
PMID- 28409652
TI - Modeling to Optimize Hospital Evacuation Planning in EMS Systems.
AB - OBJECTIVE: To develop optimal hospital evacuation plans within a large urban EMS
system using a novel evacuation planning model and a realistic hospital
evacuation scenario, and to illustrate the ways in which a decision support model
may be useful in evacuation planning. METHODS: An optimization model was used to
produce detailed evacuation plans given the number and type of patients in the
evacuating hospital, resource levels (teams to move patients, vehicles, and beds
at other hospitals), and evacuation rules. RESULTS: Optimal evacuation plans
under various resource levels and rules were developed and high-level metrics
were calculated, including evacuation duration and the utilization of resources.
Using this model we were able to determine the limiting resources and demonstrate
how strategically augmenting the resource levels can improve the performance of
the evacuation plan. The model allowed the planner to test various evacuation
conditions and resource levels to demonstrate the effect on performance of the
evacuation plan. CONCLUSION: We present a hospital evacuation planning analysis
for a hospital in a large urban EMS system using an optimization model. This
model can be used by EMS administrators and medical directors to guide planning
decisions and provide a better understanding of various resource allocation
decisions and rules that govern a hospital evacuation.
PMID- 28409653
TI - Constitutive expression of IL-22 in the human intervertebral disc and its
reduction by exposure to pro-inflammatory cytokines in vitro.
AB - The importance of cytokines in disc degeneration is well recognized. Little is
known about IL-22 expression in the human intervertebral disc. We investigated IL
22 immuno-localization in disc tissue, and molecular expression and production of
IL-22 by annulus cells cultured in three-dimensional (3D) culture. We examined
human disc tissue using immunohistochemistry and we cultured isolated annulus
cells in 3D to analyze IL-22 expression and production, and its receptor, IL-22R,
in conditioned media. Ingenuity pathway analysis (IPA) also was used to identify
significant gene expression networks within the molecular data. IL-22 and IL-22R
were immunolocalized in many cells in the human outer and inner annulus; fewer
cells exhibited localization in the nucleus. Three-dimensional culture of annulus
cells demonstrated production of IL-22 in conditioned media; exposure to IL-1beta
or TNF-alpha significantly reduced IL-22 levels. Significant decreases also were
identified in conditioned media assayed for IL-22R in TNF-alpha treated cells.
IPA analysis showed that IL-22 ranked among the top canonical pathways. We found
constitutive expression and production of IL-22 and IL-22R in the disc, which
expands our understanding of the effect of pro-inflammatory cytokines on IL-22
expression and production. Three-dimensional cultured annulus cells exposed to IL
1beta or TNF produced significantly lower levels of IL-22 into their conditioned
media compared to levels produced by control cells. Our findings have clinical
relevance because of the elevated pro-inflammatory milieu within the degenerating
human disc.
PMID- 28409654
TI - OLR1 and Loxin Expression in PBMCs of Women with a History of Unexplained
Recurrent Miscarriage: A Pilot Study.
AB - AIMS: The aim of this study was to evaluate the expression of OLR1 and its
alternative splicing isoform Loxin in unexplained recurrent miscarriage (uRM).
METHODS: Sixty-three women of reproductive age were recruited and were divided
into four groups: 18 pregnant and 23 non-pregnant women with uRM, and 12 pregnant
and 10 non-pregnant women with physiological pregnancies. Complementary DNA
derived from peripheral blood mononuclear cells (PBMCs) was analyzed by
quantitative real-time PCR to evaluate the expression of OLR1 and Loxin. Oxidized
low-density lipoproteins (ox-LDLs) were assayed from serum by a commercially
available kit. RESULTS: Pregnant uRM women presented with a higher, though not
significant, OLR1/Loxin ratio and a higher ox-LDLs serum level (p <= 0.05)
compared with pregnant control women. OLR1 and Loxin levels were significantly
decreased in non-pregnant uRM women compared with the control (OLR1: 0.00018 vs.
0.00043, p <= 0.005; Loxin: 0.00018 vs. 0.00060, p <= 0.005, respectively). Loxin
expression decreased by about two-thirds (p <= 0.005) in pregnant women compared
with non-pregnant control women. A higher expression of OLR1 in pregnant women
compared with non-pregnant women with uRM (p <= 0.05) was observed, but no
variation in Loxin expression was observed. CONCLUSIONS: The results of this
study show an association of peripheral OLR1 and Loxin expression levels in uRM
women, and they suggest the possible existence of an uncontrolled oxidative
stress in these women in the first trimester of pregnancy.
PMID- 28409655
TI - 9-1-1 Triage of Non-Traumatic Chest Pain: Association with Hospital Diagnosis.
AB - OBJECTIVE: Chest pain is one of the most common reasons people seek emergency
care-and one of the most critical. In the United States, chest pain is the second
most common reason for emergency department (ED) visits. A patient's primary
complaint of "chest pain" may reflect a broad range of underlying causes;
therefore, it is important that emergency medical service (EMS) agencies gain a
thorough understanding of these cases, beginning with the initial management of
chest pain in the 9-1-1 center. The primary objective of this study was to
compare hospital-confirmed patient discharge diagnoses to all calls handled by
emergency medical dispatchers (EMDs) using the Chest Pain/Chest Discomfort (Non
Traumatic) Chief Complaint Protocol. METHODS: The retrospective descriptive study
utilized emergency medical dispatch, EMS, and hospital datasets, collected at two
emergency communication centers in North America, from January 1, 2013 to
December 31, 2014. Patients who were dispatched using the Chest Pain/Chest
Discomfort Chief Complaint Protocol and matched to hospital datasets were
included. The primary outcome was the number and percentage of cases classified
as ischemic heart disease (IHD), other cardiac-related conditions, or non-cardiac
related conditions associated with chest pain. We also evaluated the distribution
of causes of chest pain across demographic indicators and dispatch determinants.
RESULTS: 3,007 cases were identified as "chest pain" at dispatch for which
corresponding hospital records were identified. Cases in the study were obtained
by linking EMS/Hospital and Emergency Medical Dispatch datasets. Of these cases,
47.1% (n = 1,417) were due to cardiac-related causes of chest pain, 61.5% of
which were Ischemic Heart Disease (IHD), while the rest had other cardiac-related
causes. Of the IHDs, 32.1% were Acute Myocardial Infarction (AMI). CONCLUSIONS:
Underlying causes of non-traumatic chest pain reported to 9-1-1 demonstrate a
wide range of etiologies, with a mix similar to that of chest pain patients in
several other healthcare settings, including hospital emergency departments. Most
IHD events are triaged by EMDs to the (highest) DELTA priority level, while the
CHARLIE level captures nearly all of the remaining IHD cases.
PMID- 28409656
TI - Condomless sex and HIV transmission among serodifferent couples: current evidence
and recommendations.
AB - Human immunodeficiency virus (HIV) infection remains a global pandemic. The
primary driver of HIV incidence is sexual transmission between serodifferent
individuals. Condoms, when used consistently and correctly, are effective at
preventing sexually transmitted HIV infections and are considered an integral
component of a comprehensive approach to HIV prevention. However, the
demonstrated effectiveness of antiretroviral therapy (ART) to prevent HIV
transmission, known as treatment as prevention and of pre-exposure prophylaxis,
have raised an intriguing dilemma on the necessity and additive preventive
benefit of condom use among individuals in serodifferent relationships utilizing
these prevention strategies. Recent published evidence, although of limited
follow-up duration, has shown no linked HIV transmissions with condomless sex
among serodifferent couples where the infected partner was on ART and
virologically suppressed. This paper will review the evidence surrounding HIV
transmission risk among serodifferent couples with and without the use of condoms
and will highlight factors that increase or attenuate this risk. It will also
address the important benefits that condomless sex offers couples. This paper
aims to provide a template for providers to have personalized discussions with
their patients, particularly those with an HIV-positive sexual partner, around
their individual risk of HIV transmission and the role of condom use.
PMID- 28409657
TI - Estimates of functional cerebral hemispheric differences in monolingual and
bilingual people who stutter: Dual-task paradigm.
AB - The inter-relationship of stuttering and bilingualism to functional cerebral
hemispheric processing was examined on a dual-task paradigm. Eighty native German
(L1) speakers, half of whom were sequential bilinguals (L2 = English), were
recruited. The participants (mean age = 38.9 years) were organised into four
different groups according to speech status and language ability: 20 bilinguals
who stutter (BWS), 20 monolinguals who stutter (MWS), 20 bilinguals who do not
stutter (BWNS), and 20 monolinguals who do not stutter (MWNS). All participants
completed a dual-task paradigm involving simultaneous speaking and finger
tapping. No performance differences between BWS and BWNS were found. In contrast,
MWS showed greater dual-task interference compared to BWS and MWNS, as well as
greater right- than left-hand disruption. A prevailing finding was that
bilingualism seems to offset deficits in executive functioning associated with
stuttering. Cognitive reserve may have been reflected in the present study,
resulting in a bilingual advantage.
PMID- 28409658
TI - Lack of Preventive Health Behaviors in the Early Forties: The Role of Earlier
Trajectories of Cigarette Smoking From Adolescence to Adulthood.
AB - OBJECTIVE: To study the degree to which individuals in different trajectories of
cigarette smoking from adolescence to the early forties are similar or different
in terms of lack of preventive health behaviors (e.g., underuse of preventive
health services, unhealthy eating habits) in early midlife. METHODS: Participants
came from a community-based random sample of residents in two upstate New York
counties (N = 548). Data were collected from adolescence to early midlife (mean
age = 43 years, standard deviation [SD] = 2.8) at seven time points. Using growth
mixture modeling, we statistically identified the number of smoking trajectories.
Logistic regression analysis was used to study the relationship between the
probabilities of participants' smoking trajectory group membership and lack of
preventive behaviors in early midlife. RESULTS: Five trajectory groups of
cigarette smokers were identified. With controls, as compared with the nonsmoker
trajectory group, higher probabilities of belonging to the heavy/continuous
smoker trajectory group and the late starter trajectory groups were significantly
associated with a higher likelihood of lack of preventive health behaviors
(adjusted odds ratio [AOR] = 3.49 and 4.02 respectively). In addition, as
compared to the quitter/decreaser trajectory group, higher probabilities of
belonging to the heavy/continuous smoker trajectory group and the late starter
trajectory group were also significantly associated with a higher likelihood of
lack of preventive health behaviors (AOR = 3.51 and 4.04 respectively).
CONCLUSIONS: Intervention programs may consider focusing on heavy/continuous
smokers and late starters in programs designed to promote adequate use of
preventive health services and healthy general lifestyles in early midlife.
PMID- 28409659
TI - The Relationship Between Caffeine Intake and Immunological and Virological
Markers of HIV Disease Progression in Miami Adult Studies on HIV Cohort.
AB - Although there are many studies on adverse health effects of substance use and
HIV disease progression, similar studies about caffeine consumption are few. In
this study, we investigated the effects of caffeine on immunological and
virological markers of HIV disease progression. A convenience sample of 130
clinically stable people living with HIV/AIDS on antiretroviral therapy (65
consuming <=250 mg/day and 65 consuming >250 mg/day of caffeine) were recruited
from the Miami Adult Studies on HIV (MASH) cohort. This study included a baseline
and 3-month follow-up visit. Demographics, body composition measures, substance
use, Modified Caffeine Consumption Questionnaire (MCCQ), and CD4 count and HIV
viral load were obtained for all participants. Multivariable linear regression
and Linear Mixed Models (LMMs) were used to understand the effect of caffeine
consumption on CD4 count and HIV viral load. The mean age of the cohort was 47.9
+/- 6.4 years, 60.8% were men and 75.4% were African Americans. All participants
were on ART during both the visits. Mean caffeine intake at baseline was 337.6 +/
305.0 mg/day and did not change significantly at the 3-month follow-up visit.
Multivariable linear regressions after adjustment for covariates showed
significant association between caffeine consumption and higher CD4 count (beta =
1.532, p = 0.049) and lower HIV viral load (beta = -1.067, p = 0.048). LMM after
adjustment for covariates showed that the relationship between caffeine and CD4
count (beta = 1.720, p = 0.042) and HIV viral load (beta = -1.389, p = 0.033)
continued over time in a dose-response manner. Higher caffeine consumption was
associated with higher CD4 cell counts and lower HIV viral loads indicating
beneficial effects on HIV disease progression. Further studies examining
biochemical effects of caffeine on CD4 cell counts and viral replication need to
be done in the future.
PMID- 28409660
TI - A Randomized, Double-Blind Placebo-Controlled Trial on Effectiveness and Safety
of Celecoxib Adjunctive Therapy in Adolescents with Acute Bipolar Mania.
AB - OBJECTIVE: Recent studies have focused on the role of inflammatory cascades as
one of the possible etiologic factors of bipolar disorder. We hypothesize that
celecoxib, through its anti-inflammatory properties, may have a therapeutic role
in acute bipolar mania. PATIENTS AND METHODS: Forty-two adolescent inpatients
with the diagnosis of acute bipolar mania participated in a parallel, randomized,
double-blind controlled trial, and 40 patients underwent an 8-week treatment with
either celecoxib (100 mg twice daily) or placebo as an adjunctive treatment to
lithium and risperidone. Patients were evaluated using Young Mania Rating Scale
(YMRS) at baseline and weeks 2, 4, and 8. The primary outcome measure was to
assess the efficacy of celecoxib compared with placebo in improving mania
symptoms. RESULT: General linear model repeated measures showed significant
effect for time * treatment interaction on YMRS scores [F (2.54, 96.56) = 3.21, p
= 0.03]. Significantly greater improvement was observed in YMRS scores in the
celecoxib group compared with the placebo group from baseline YMRS score at week
8 (p = 0.04). Although a 35% greater response to treatment (considering a
Clinical Global Impressions-Improvement score of <=2, very much/much improved)
was observed in the celecoxib group compared with the placebo group, the
difference did not reach the statistical significance level (p = 0.09). No
serious adverse event was reported. CONCLUSIONS: Celecoxib may be an effective
adjuvant therapy in treatment of manic episodes (without psychotic features) of
adolescents with bipolar mood disorder. The mood-stabilizing role of this drug
might be mediated through its action on inflammatory cascades.
PMID- 28409661
TI - Adverse neonatal outcomes in relation to ambient temperatures at birth: A
nationwide survey in Taiwan.
AB - This study investigated the temperature-specific risks of adverse neonatal
outcomes in Taiwan. Over 2 million births between 2001 and 2010 were correlated
with the daily mean outdoor temperatures at birth. A log-binomial model was used
to estimate the risk of adverse neonatal outcomes in relation to ambient
temperature at birth after adjusting for possible confounders. There was a
significant correlation of temperature extremes with stillbirth, preterm birth,
and low birth weight. Maternal exposure to temperature extremes carried greater
risks of stillbirth (> 23.4 degrees C), preterm birth (< 19.5 degrees C and >
25.4 degrees C), and low birth weight (< 15.5 degrees C and > 23.4 degrees C)
than did temperatures of 21.5 degrees C~23.4 degrees C. In conclusion, infants
born to women exposed to temperature extremes possess greater risks for
stillbirth, preterm birth, and low birth weight. The data suggest optimal
temperatures to minimize overall adverse neonatal outcomes are 21.5 degrees
C~23.4 degrees C.
PMID- 28409662
TI - Association of Endothelial Nitric Oxide Synthase Gene Polymorphism with
Susceptibility and Nephritis Development of Henoch-Schonlein Purpura in Chinese
Han Children.
AB - OBJECTIVE: Henoch-Schonlein purpura (HSP) is the most common form of systemic
small-vessel vasculitis in children. Previous studies suggested endothelial
nitric oxide synthase (eNOS) plays an important role in the pathogenesis and
clinical manifestations of HSP. This study aimed to investigate the potential
association between 10 single-nucleotide polymorphisms (SNPs) within the eNOS
gene and HSP risk and nephritis development in a Chinese Han population.
MATERIALS AND METHODS: A case-control study was conducted including 459 healthy
children and 423 children with HSP. SNPs were genotyped by using the MassARRAY
system. RESULTS: The genotypic frequency of rs11771443 was nominally associated
with the risk of HSP (p = 0.010), and the C allele significantly increased the
risk of HSP (p = 0.003, odds ratio [OR] = 1.331, confidence interval [95% CI] =
1.104-1.605). There was a significant difference in allelic and genotypic
distribution of rs1799983 between children with HSP and healthy controls (p =
0.002 and 0.0001, respectively). Strong linkage disequilibrium was observed in
two blocks. Significantly fewer T-A-G haplotypes (p = 0.0001, OR = 0.593, 95% CI
= 0.448-0.786) were found in children with HSP. No significant association was
identified between the 10 SNPs and the pathogenesis of HSP progression to HSP
nephritis (HSPN). CONCLUSIONS: The polymorphisms of eNOS contribute to genetic
susceptibility to HSP, but may have no effect on children with HSP progressing to
HSPN.
PMID- 28409663
TI - Prevalence and risk factors of musculoskeletal symptoms among dental students and
dental practitioners in Riyadh City, Saudi Arabia.
AB - This study assessed the nature, prevalence, and risk factors of musculoskeletal
symptoms (MS) in dental clinics. A self-administered questionnaire was completed
by 515 dental students and dentists about nature of work and prevalence and
frequency of MS symptoms. Chi-square and logistic regression were used to
determine the association of MS with a number of important variables. Pain in the
lower back (64%) and neck (60%) were the most prevalent MS. Working in the dental
colleges' clinics was associated with increased risk of MS (adjusted OR 2.30, 95%
CI [1.27, 4.18]). A stronger association was observed for dentists working in the
private clinics (adjusted OR 2.58, 95% CI [1.28, 5.17]). Female dentists were at
more risk of MS than male participants (OR 1.63, 95% CI [1.02, 2.59]). The higher
risk of reported MS symptoms in women and for those working in the dental
colleges and private clinics underscores the importance of recognition and
prevention of MS symptoms even early in the dental profession.
PMID- 28409664
TI - Longitudinal changes in polysyllable maturity of preschool children with
phonologically-based speech sound disorders.
AB - Children's polysyllables were investigated for changes in (1) consonant and vowel
accuracy, (2) error frequency and (3) polysyllable maturity over time.
Participants were 80 children (4;0-5;4) with phonologically-based speech sound
disorders who participated in the Sound Start Study and completed the
Polysyllable Preschool Test (Baker, 2013) three times. Polysyllable errors were
categorised using the Word-level Analysis of Polysyllables (WAP, Masso, 2016a)
and the Framework of Polysyllable Maturity (Framework, Masso, 2016b), which
represents five maturity levels (Levels A-E). Participants demonstrated increased
polysyllable accuracy over time as measured by consonant and vowel accuracy, and
error frequency. Children in Level A, the lowest level of maturity, had frequent
deletion errors, alterations of phonotactics and alterations of timing.
Participants in Level B were 8.62 times more likely to improve than children in
Level A at Time 1. Children who present with frequent deletion errors may be less
likely to improve their polysyllable accuracy.
PMID- 28409665
TI - Monoclonal Antibody Against Premembrane Viral Protein of Avian Tembusu Virus.
AB - Premembrane (prM) is a viral protein of flavivirus, which is important for the
generation of infectious virion and for virus infection to the host. However, the
biological properties and function of the prM of Avian Tembusu virus (ATMUV) have
scarcely been studied to date. Monoclonal antibodies (mAbs) are a powerful tool
for functional analysis of viral protein. To produce a mAb against prM protein of
ATMUV, the prM gene sequence was amplified by reverse transcription polymerase
chain reaction (RT-PCR) and cloned into the prokaryotic expression vector pET-28a
(+). The recombinant prM protein was successfully expressed in BL21 (DE3). Using
the purified prM as immunogen in mice, three hybridoma cells secreting mAbs
against prM protein were obtained. These mAbs showed a strong reaction with ATMUV
infected DF-1 cells and pEGFP-C3-prM transfected 293-T cells in both Western
blotting analysis and immunofluorescence assay. The mAbs developed in this study
will be useful tools for analysis of the prM protein functions on ATMUV infection
and the interaction between prM and its host molecules.
PMID- 28409666
TI - Evaluating the Feasibility of Single Incision Laparoscopic Appendectomy Performed
by a Resident Based on Propensity Score Matching.
AB - PURPOSE: Conventional laparoscopic appendectomy (CLA) has been considered the
standard for the treatment of acute appendicitis. Recently, single incision
laparoscopic appendectomy (SILA) has become an alternative option. There are few
reports on the results of SILA performed by residents during the training period.
The present study, we report our residents' experience. MATERIALS AND METHODS: We
reviewed clinical characteristics and outcomes of 1005 patients who underwent
appendectomy between October 2013 and April 2016. Every operation was performed
by only residents. Clinical characteristics and operative outcomes between SILA
and CLA group were reviewed after propensity score matching. RESULTS: SILA was
used more frequently in younger patients (23.3 versus 36.4 years, P = .000),
women (66.4% versus 45.9%, P = .000), and patients with lower body mass index
(20.2 versus 22.9 kg/m2, P = .043). After propensity score matching, the rate of
complicated appendicitis was lower (12.9% versus 15.5%, P = .573), and the mean
operative time was slightly shorter in the SILA group than in the CLA group
(56.68 versus 59.09 minutes, P = .068), although these differences were not
statistically significant. There were no significant differences between the two
groups in hospitalization period (2.7 versus 2.9 days, P = .380), the use of
analgesics (2.0 versus 2.1 times, P = .128), and wound complication rate (10.3%
versus 14.6%, P = .333). CONCLUSION: It is a safe and relatively easy procedure
with an acceptable postoperative cosmetic outcome that can be incorporated into
the routine surgical training.
PMID- 28409668
TI - Communication and collaboration in spine neuromonitoring: time to expect more, a
lot more, from the neurophysiologists.
PMID- 28409669
TI - Treatment of thoracolumbar burst fractures: extended follow-up of a randomized
clinical trial comparing orthosis versus no orthosis.
AB - OBJECTIVE A multicenter, prospective, randomized equivalence trial comparing a
thoracolumbosacral orthosis (TLSO) to no orthosis (NO) in the treatment of acute
AO Type A3 thoracolumbar burst fractures was recently conducted and demonstrated
that the two treatments following an otherwise similar management protocol are
equivalent at 3 months postinjury. The purpose of the present study was to
determine whether there was a difference in long-term clinical and radiographic
outcomes between the patients treated with and those treated without a TLSO.
Here, the authors present the 5- to 10-year outcomes (mean follow-up 7.9 +/- 1.1
years) of the patients at a single site from the original multicenter trial.
METHODS Between July 2002 and January 2009, a total of 96 subjects were enrolled
in the primary trial and randomized to two groups: TLSO or NO. Subjects were
enrolled if they had an AO Type A3 burst fracture between T-10 and L-3 within the
previous 72 hours, kyphotic deformity < 35 degrees , no neurological deficit, and
an age of 16-60 years old. The present study represents a subset of those
patients: 16 in the TLSO group and 20 in the NO group. The primary outcome
measure was the Roland Morris Disability Questionnaire (RMDQ) score at the last 5
to 10-year follow-up. Secondary outcome measures included kyphosis,
satisfaction, the Numeric Rating Scale for back pain, and the 12-Item Short-Form
Health Survey (SF-12) Mental and Physical Component Summary (MCS and PCS) scores.
In the original study, outcome measures were administered at admission and 2 and
6 weeks, 3 and 6 months, and 1 and 2 years after injury; in the present extended
follow-up study, the outcome measures were administered 5-10 years postinjury.
Treatment comparison between patients in the TLSO group and those in the NO group
was performed at the latest available follow-up, and the time-weighted average
treatment effect was determined using a mixed-effects model of longitudinal
regression for repeated measures averaged over all time periods. Missing data
were assumed to be missing at random and were replaced with a set of plausible
values derived using a multiple imputation procedure. RESULTS The RMDQ score at 5
10 years postinjury was 3.6 +/- 0.9 (mean +/- SE) for the TLSO group and 4.8 +/-
1.5 for the NO group (p = 0.486, 95% CI -2.3 to 4.8). Average kyphosis was 18.3
degrees +/- 2.2 degrees for the TLSO group and 18.6 degrees +/- 3.8 degrees
for the NO group (p = 0.934, 95% CI -7.8 to 8.5). No differences were found
between the NO and TLSO groups with time-weighted average treatment effects for
RMDQ 1.9 (95% CI -1.5 to 5.2), for PCS -2.5 (95% CI -7.9 to 3.0), for MCS -1.2
(95% CI -6.7 to 4.2) and for average pain 0.9 (95% CI -0.5 to 2.2). CONCLUSIONS
Compared with patients treated with a TLSO, patients treated using early
mobilization without orthosis maintain similar pain relief and improvement in
function for 5-10 years.
PMID- 28409670
TI - Erratum. Hospital charges associated with "never events": comparison of anterior
cervical discectomy and fusion, posterior lumbar interbody fusion, and lumbar
laminectomy to total joint arthroplasty.
PMID- 28409671
TI - The mediating role of placenta in the relationship between maternal exercise
during pregnancy and full-term low birth weight.
AB - OBJECTIVE: To explore the association of maternal exercise during pregnancy with
full-term low birth weight (FT-LBW) and whether placenta mediates their
association. STUDY DESIGN: We investigated 326 pregnant women delivering FT-LBW
weight newborns (cases) and 1644 delivering full-term normal birth weight
newborns (controls) in this case-control study. Information concerning maternal
exercise during pregnancy, socio-demographics and obstetric characteristics were
collected at Women and Children's Hospitals of Shenzhen and Foshan in Guangdong,
China. RESULTS: After adjusting for the potential confounders, maternal exercise
frequency and duration during pregnancy were significantly negatively associated
with FT-LBW, respectively. Moreover, compared with mothers taking no exercise
during pregnancy, those taking exercises were significantly negatively associated
with FT-LBW except those taking low/medium frequency and short duration exercise
and high-frequency and long duration exercise, and their adjusted ORs ranged from
0.30 to 0.62. Furthermore, mediation analysis illustrated that placental weight
partially mediated 27.20% of the association between maternal exercise frequency
during pregnancy and FT-LBW, but not the association between maternal exercise
duration during pregnancy and FT-LBW. CONCLUSIONS: Maternal exercise during
pregnancy is beneficial for lowering FT-LBW risk, especially when taking
appropriate and enough exercise. Placenta weight partially mediates the
association between maternal exercise frequency during pregnancy and FT-LBW.
PMID- 28409672
TI - Making a Difference: A Study of Cognitive Stimulation Therapy for Persons with
Dementia.
AB - Affecting nearly 5.4 million older adults in the United States and 35.6 million
individuals worldwide, dementia is one of the greatest public health crises of
our time. As a result, helping professionals, clients, and care partners seek
effective and affordable treatment. Developed in the United Kingdom by Spector
and colleagues, Cognitive Stimulation Therapy (CST) is a non-pharmacologic
psychosocial group intervention for persons with dementia. To expand upon and
fill the gaps within existing research, the authors developed a descriptive study
to assess the impact of CST on cognition, quality of life, and depression, among
six CST groups (n = 40). A paired sample t-test was run among pre- and post-test
measures. There was a statistically significant difference in Saint Louis
University Mental Status Exam (SLUMS) scores after CST (t = 2.80, p = 0.008).
There was also a statistically significant difference in Cornell Scale for
Depression in Dementia scores (t = -3.36, p = 0.002). There was no statistically
significant difference in Quality of Life scores.
PMID- 28409673
TI - "Como Si Nada": Enduring Violence and Diabetes among Rural Women in Southern
Mexico.
AB - Rural women in Southern Mexico link their diabetes to distressful life
experiences rooted in ordinary violence. While much has been written on the use
that diabetes sufferers make of their morbid condition as an idiom of distress, I
investigate the personal and social effects that such an idiom has on women. As I
illustrate, diabetes reflects an ambivalence that helps women to speak about the
unspeakable and, at the same time, reinforces their ideas of culpability, namely
that they are to blame for both the gendered violence that they endure and the
diabetes from which they suffer.
PMID- 28409674
TI - Comparing Rural and Urban Cervical and Breast Cancer Screening Rates in a
Privately Insured Population.
AB - Low preventive screening varies by region and contributes to poor outcomes for
breast and cervical cancer. Previous comparative urban and rural research on
preventive screening has focused on government programs. This study quantified
and compared rural and urban preventive cancer screening rates for women who were
privately insured. National Quality Forum measures were used to calculate rates
for women within rural and urban parts of the same Hospital Referral Region (HRR)
using claims data. Mammography screening rates for women age 24 to 69 years were
77.1% in 2011 and 76.1% in 2008. Compared to urban women, mammography screening
rates for women visiting rural physicians were lower in 42%, higher in 2% and
identical in 56% of HRRs. Cervical cancer screening rates for women age 21 to 64
years were 82.9% in 2011 and 83.5% in 2008. Cervical cancer screening rates among
women who saw rural physicians were lower in 55%, higher in 4%, and identical in
42% of HRRs. HRRs where rural areas underperformed urban areas increased between
2008 and 2011 for both screenings. Moderate but notable differences in women's
preventive screening rates between rural and urban physicians highlight the need
for practical solutions that increase use of screening services and reduce
barriers to services in rural areas.
PMID- 28409675
TI - Driving violations and health promotion behaviors among undergraduate students:
Self-report of on-road behavior.
AB - INTRODUCTION: The purposes of this study are to characterize Israeli
undergraduate students' driving violations in the terms of problem behavior
theory and to identify whether there is any relationship between driving
violations and health risk behaviors, daring behaviors, excitement seeking, and
health promotion behaviors. METHODS: This study is based on a structured self
reported anonymous questionnaire distributed to undergraduate students in an
academic institution. The sample included 533 undergraduate students (374 females
and 159 males). The mean age was 23.4 (SD = 1.4, range = 5). RESULTS: A higher
prevalence of self-reported driving violations was found among males in
comparison to females. All substance use measures were positively related to
driving violations; for example, use of cigarettes (OR = 4.287, P <.001) and
water pipes (odds ratio [OR] = 3.000, P <.001) as well as binge drinking (OR =
5.707, P <.001) and regular cannabis smoking (OR = 5.667, P <.001) raise the
probability of committing rare driving violations. The strongest predictive
factors for the frequent driving violations group were alcohol consumption
related variables: binge drinking (OR = 2.560, P <.01) and drunkenness (OR =
2.284, P <.05). Strong odd ratios were also found between the frequent driving
violations group and selling or dealing drugs (12.143, P <.001), and stealing
something valuable (13.680, P <.001). The strongest predicted variable for the
rare driving violations group was physical confrontation due to verbal
disagreement (3.439, P <.05) and the concept that selling or dealing drugs is
socially acceptable (2.521, P <.05). The probability of executing rare driving
violations was higher for subjects who reported intense physical workout regimens
(OR = 1.638, P <.05). CONCLUSIONS: Problem behavior theory succeeded in
explaining health risk behavior and driving violations. This study shows that
bachelors tend to be more involved in risk behaviors, such as substance use,
excitement-seeking behaviors, and daring behaviors and are active physically and
thus constitute a risk group for driving violations. As such, intervention
resources should be directed toward this group.
PMID- 28409676
TI - Analysis of risk factors for persistent infection of asymptomatic women with high
risk human papilloma virus.
AB - OBJECTIVE: This study aims to prevent persistentinfection, reduce the incidence
of cervical cancer, and improve women's health by understanding the theoretical
basis of the risk factors for continuous infection of asymptomatic women with
high-risk human papilloma virus (HPV) strains via information collected, which
includes the persistent infection rate and the most prevalent HPV strain types of
high risk to asymptomatic women in the high-risk area of cervical cancer in
Linfen, Shanxi Province. METHODS: Based on the method of cluster sampling,
locations were chosen from the industrial county and agricultural county of
Linfen, Shanxi Province, namely the Xiangfen and Quwo counties. Use of the
convenience sampling (CS) method enables the identification of women who have sex
but without symptoms of abnormal cervix for analyzing risk factors of HPV-DNA
detection and performing a retrospective questionnaire survey in these 2
counties. Firstly, cervical exfoliated cell samples were collected for thin-layer
liquid-based cytology test (TCT), and simultaneously testing high-risk type HPV
DNA, then samples with positive testing results were retested to identify the
infected HPV types. The 6-month period of testing was done to derive the 6-month
persistent infection rate. The retrospective survey included concepts addressed
in the questionnaire: basic situation of the research objects, menstrual history,
marital status, pregnancy history, sexual habits and other aspects. The
questionnaire was divided into a case group and a comparison group, which are
based on the high-risk HPV-DNA testing result to ascertain whether or not there
is persistent infection. Statistical analysis employed Epidate3.1 software for
date entry, SPSS17.0 for date statistical analysis. Select statistic charts, Chi
Square Analysis, single-factor analysis and multivariate Logistic regression
analysis to analyze the protective factors and risk factors of high-risk HPV
infection. Risk factors are predicted by using the classification tree. RESULTS:
3000 women participated in the study. The high-risk type HPV infection rate was
8.7%, the persistent infection rate was 7.5%. The persistent infection rates for
the 2 age groups (ages 18-26 and 27-30) were 6.9% and 8.7%. The persistent
infection rates of Xiangfen county were 7.4% and 7.4% respectively, and those of
Quwo county were 7.8% and 11.6% respectively; there was no significant difference
between each pair of groups. Single risk-factor analysis showed that first-time
sex at age under 20, high school/technical secondary school education or above,
multiple sexual partners, having more than 2 sexual partners in the past 6
months, oral sex, and colitis are the risk factors of high-risk type HPV
infection. Multivariate analysis showed that the number of sexual partners,
smoking and oral sex had an effect on HPV infection. The risk of HPV infection
from smoking was 5.0-fold higher, and the risk of HPV infection from oral sex was
6.1-fold higher. Having more than 2 sexual partners increase the risk of HPV
infection. By the predicated model analysis, the probability of HPV conveyed by
oral sex was 14.8%; if the sexual companion number was zero or more than 2
without oral sex, the probability of HPV infection was 12.1%; if there was one
sexual partner who smokes without oral sex, the probability of infection was
18.6%; if there was one sexual partner who does not smoke and without oral sex,
the probability of infection was 3.6%. CONCLUSION: The persistent infection rate
of asymptomatic women for high-risk type HPV is lower than those women in all
ages. High-risk type HPV infection risk factors include the number of sexual
partners, oral sex and smoking. Thus, young women may be able to reduce the risk
of infection with high-risk type HPV by reducing the number of sexual partners,
forming a correct sexual life habit, and avoiding smoking.
PMID- 28409677
TI - Circadian pattern of motor activity in adults with attention
deficit/hyperactivity disorder.
AB - This study aims to describe the 24-hour activity rhythm in adults with attention
deficit/hyperactivity disorder (ADHD). A total of 18 ADHD patients and 37 healthy
controls (HCs) wore an actigraph for 7 days. ADHD patients showed higher motor
activity than HCs at 4:00, 6:00, 15:00 and 16:00 hour. Within the theoretical
framework of the two-process model of sleep regulation, the observed data may be
explained by lower homeostatic sleep pressure in ADHD. This could lead to an
increase in motor activity in the second half of the night, when sleep need
decreases more rapidly, and in the first half of the afternoon, when patients do
not experience the typical post-lunch dip.
PMID- 28409678
TI - A Hairline Crack in the Levee: Focal Secretory IgA Deficiency as a First Step
toward Emphysema.
PMID- 28409679
TI - Continuous or Extended Intravenous Administration of beta-Lactam Antibiotics.
PMID- 28409681
TI - Airway Remodeling in Asthma: Is it Fixed or Variable?
PMID- 28409680
TI - Fluctuation Metrics as Novel Endpoints for Clinical Trials in Asthma.
PMID- 28409682
TI - Distinct Serum Sphingolipid Profiles among School-aged Children with Exercise
induced Wheeze and Asthma Persistence.
PMID- 28409683
TI - Choosing Sides in Predicting Fluid Responsiveness.
PMID- 28409684
TI - What is Bronchiectasis?
PMID- 28409685
TI - Monitoring of Pneumothorax Appearance with Electrical Impedance Tomography during
Recruitment Maneuvers.
PMID- 28409686
TI - The Canary in the Coal Mine Is Coughing: Electronic Cigarettes and Respiratory
Symptoms in Adolescents.
PMID- 28409687
TI - The Evolving Role of the Indwelling Tunneled Pleural Catheter. A Means to an End.
PMID- 28409688
TI - Effect of exercise during pregnancy to prevent gestational diabetes mellitus: a
systematic review and meta-analysis.
AB - INTRODUCTION: Exercise showed some potential in preventing gestational diabetes
mellitus. However, the results remained controversial. We conducted a systematic
review and meta-analysis to evaluate the impact of exercise during pregnancy on
gestational diabetes mellitus. METHODS: PubMed, EMbase, Web of science, EBSCO,
and Cochrane library databases were systematically searched. Randomized
controlled trials (RCTs) assessing the influence of exercise during pregnancy on
gestational diabetes mellitus were included. Two investigators independently
searched articles, extracted data, and assessed the quality of included studies.
The primary outcome was the incidence of gestational diabetes mellitus. Meta
analysis was performed using random-effect model. RESULTS: Six RCTs involving
2164 patients were included in the meta-analysis. Compared with control
intervention, exercise intervention was associated with significantly decreased
incidence of gestational diabetes mellitus (Std. mean difference = 0.59; 95%CI =
0.39-.88; p = .01), but had no effect on gestational age at birth (Std. mean
difference = -0.03; 95%CI = -0.12 to 0.07; p = .60), the number of preterm birth
(OR = 0.85; 95%CI = 0.43-1.66; p = .63), glucose 2-h post-OGTT (Std. mean
difference = -1.02; 95%CI = -2.75 to 0.71; p = .25), birth weight (Std. mean
difference = -0.13; 95%CI = -0.26 to 0.01; p = .06), and Apgar score less than 7
(OR = .78; 95%CI = 0.21-2.91; p = .71). CONCLUSIONS: Compared to control
intervention, exercise intervention could significantly decrease the risk of
gestational diabetes mellitus, but showed no impact on gestational age at birth,
preterm birth, glucose 2-h post-OGTT, birth weight, and Apgar score less than 7.
PMID- 28409689
TI - Effects of methoxychlor on IGF-I signaling pathway in rat ovary.
AB - Follicular development and other ovarian functions are regulated by growth
factors that can be affected by exogenous agents. Methoxychlor (MXC) is an
organochloride pesticide that causes female infertility. We investigated how MXC
affects the distribution of developing ovarian follicles in adult rats after
treatment between embryonic day (E) 18 and postnatal day (PND) 7. We also
measured insulin-like growth factor-I (IGF-I) and its receptor, IGF-IR,
expressions in ovarian follicles and investigated whether MXC changed the levels
of IGF-I and IGF-IR in the ovary. Using immunohistochemical (IHC) staining, we
detected IGF-I expression in oocytes and granulosa cells of the follicles, luteal
cells, interstitial cells, theca externa and theca interna, and the smooth muscle
of ovarian vessels. IGF-IR was co-localized with IGF-I in the ovary except for
the theca externa. IGF-I expression was decreased in granulosa cells of preantral
and antral follicles after treatment with MXC compared to granulosa cells of
preantral and antral follicles of the control group. We also observed that
oocytes of secondary follicles and granulosa cells of secondary and preantral
follicles of the MXC treated groups showed increased IGF-IR expression compared
to oocytes of secondary follicles and granulosa cells of secondary and preantral
follicles of the control group. We also detected more secondary and preantral
follicles, and fewer primordial and antral follicles after MXC administration
compared to controls. Therefore, the IGF signaling pathway may participate in MXC
induced ovary dysfunction and female infertility.
PMID- 28409690
TI - Salivary cortisol concentration after high-intensity interval exercise: Time of
day and chronotype effect.
AB - Due to personal and working necessities, the time for exercise is often short,
and scheduled early in the morning or late in the afternoon. Cortisol plays a
central role in the physiological and behavioral response to a physical challenge
and can be considered as an index of exercise stress. Therefore, the aim of this
study was to evaluate the influence of the circadian phenotype classification on
salivary cortisol concentration in relation to an acute session of high-intensity
interval exercise (HIIE) performed at different times of the day. Based on the
morningness-eveningness questionnaire, 12 M-types (N = 12; age 21 +/- 2 years;
height 179 +/- 5 cm; body mass 74 +/- 12 kg, weekly training volume 8 +/- 1
hours) and 11 E-types (N = 11; age 21 +/- 2 years; height 181 +/- 11 cm; body
mass 76 +/- 11 kg, weekly training volume 7 +/- 2 hours) were enrolled in a
randomized crossover study. All subjects underwent measurements of salivary
cortisol secretion before (PRE), immediately after (POST), and 15 min (+15 min),
30 min (+30 min), 45 min (+45 min) and 60 min (+60 min) after the completion of
both morning (08.00 am) and evening (08.00 p.m.) high-intensity interval
exercise. Two-way analysis of variance with Tuckey's multiple comparisons test
showed significant increments over PRE-cortisol concentrations in POSTcondition
both in the morning (4.88 +/- 1.19 ng . mL-1 vs 6.60 +/- 1.86 ng . mL-1, +26.1%,
P < 0.0001, d > 0.8) and in the evening (1.56 +/- 0.48 ng . mL-1 vs 2.34 +/-
0.37, +33.4%, P = 0.034, d > 0.6) exercise in all the 23 subject that performed
the morning and the evening HIIE. In addition, during morning exercise,
significant differences in cortisol concentration between M-types and E-types at
POST (5.49 +/- 0.98 ng . mL-1 versus 8.44 +/- 1.08 ng . mL-1, +35%, P < 0.0001, d
> 0.8), +15 min (4.52 +/- 0.42 ng . mL-1 versus 6.61 +/- 0.62 ng . mL-1, +31.6%,
P < 0.0001, d > 0.8), +30 min (4.10 +/- 1.44 ng . mL-1 versus 6.21 +/- 1.60 ng .
mL-1, +34.0%, P < 0.0001, d = 0.7), + 45 min (3.78 +/- 0.55 ng . mL-1 versus 5.80
+/- 0.72 ng . mL-1, +34.9%, P < 0.0001, d = 0.7), and + 60 min condition(3.53 +/-
0.45 ng . mL-1 versus 5.78 +/- 1.13 ng . mL-1, 38.9%, P = 0.0008, d = 0.7) were
noted. No statistical significant differences between M-types and E-types during
evening HIIE on post-exercise cortisol concentration were detected. E-types
showed a higher morning peak of salivary cortisol respect to M-types when
performing a HIIE early in the morning and produced higher salivary cortisol
concentrations after the cessation of the exercise. Practical applications
suggest that it is increasingly important for the exercise professionals to
identify the compatibility between time of day for exercising and chronotype to
find the individual's favorable circadian time to perform a HIIE.
PMID- 28409691
TI - To the Editor: Concerning Kaya et al.
PMID- 28409692
TI - Validation and norming of the Intelligibility in Context Scale in Northern Viet
Nam.
AB - Vietnamese is one of the 20 most commonly spoken languages in the world; however,
there are no standardised tools to assess Vietnamese children's speech. This
study aimed to validate and norm the Vietnamese version of the Intelligibility in
Context Scale (ICS-VN). Data were collected from parents of 181 children (aged
2;0-5;11) living in Ha Noi, Northern Viet Nam. The mean ICS-VN score was 4.43
(out of a maximum of 5), indicating that children were 'usually' to 'always'
intelligible; however, item-level scores demonstrated significant differences
between communication partners. Children with parental concerns about speech and
language had significantly lower mean scores than children without parental
concerns. Scores also differed by children's age, parents' occupation and
mothers' education level but not by sex of child or fathers' education level. The
ICS-VN had good psychometric properties indicating it to be a valid tool for use
with Vietnamese-speaking children in Northern Viet Nam.
PMID- 28409694
TI - Immunohistochemical localization of irisin in mole rats (Spalax leucodon).
AB - Irisin was first identified in skeletal muscle cells. It is an exercise protein
that is secreted into the circulation; it causes conversion of white adipose
tissue to brown adipose tissue. We investigated irisin immunoreactivity in mole
rat (Spalax leucodon) tissues. We examined cerebellum, pituitary, heart, liver,
pancreas, spleen, uterus, kidney and striated muscle in female adult mole rats.
Tissues were processed, embedded in paraffin, sectioned at 5 MUm and stained
immunohistochemically for irisin. Irisin immunostaining was detected in the
cytoplasm of stained cells; the cytoplasm of Purkinje cells was unstained. We
found that irisin may be synthesized in many tissues. The function of locally
synthesized irisin currently is unknown.
PMID- 28409693
TI - TPT1 (tumor protein, translationally-controlled 1) negatively regulates autophagy
through the BECN1 interactome and an MTORC1-mediated pathway.
AB - TPT1/TCTP (tumor protein, translationally-controlled 1) is highly expressed in
tumor cells, known to participate in various cellular activities including
protein synthesis, growth and cell survival. In addition, TPT1 was identified as
a direct target of the tumor suppressor TP53/p53 although little is known about
the mechanism underlying the anti-survival function of TPT1. Here, we describe a
role of TPT1 in the regulation of the MTORC1 pathway through modulating the
molecular machinery of macroautophagy/autophagy. TPT1 inhibition induced cellular
autophagy via the MTORC1 and AMPK pathways, which are inhibited and activated,
respectively, during treatment with the MTOR inhibitor rapamycin. We also found
that the depletion of TPT1 potentiated rapamycin-induced autophagy by synergizing
with MTORC1 inhibition. We further demonstrated that TPT1 knockdown altered the
BECN1 interactome, a representative MTOR-independent pathway, to stimulate
autophagosome formation, via downregulating BCL2 expression through activating
MAPK8/JNK1, and thereby enhancing BECN1-phosphatidylinositol 3-kinase (PtdIns3K)
UVRAG complex formation. Furthermore, reduced TPT1 promoted autophagic flux by
modulating not only early steps of autophagy but also autophagosome maturation.
Consistent with in vitro findings, in vivo organ analysis using Tpt1 heterozygote
knockout mice showed that autophagy is enhanced because of haploinsufficient TPT1
expression. Overall, our study demonstrated the novel role of TPT1 as a negative
regulator of autophagy that may have potential use in manipulating various
diseases associated with autophagic dysfunction.
PMID- 28409695
TI - Characterization of a Monoclonal Antibody Specific for the Growth Hormone
Secretagogue Receptor.
AB - Ghrelin is an orexigenic peptide hormone that primarily regulates growth hormone
secretion, food intake, and energy homeostasis. It has been shown to also play a
role in numerous higher brain functions, such as the regulation of inflammation
and cell proliferation. Ghrelin is the endogenous ligand of the growth hormone
secretagogue receptor (GHSR), a G-protein-coupled receptor highly expressed in
brain and detectable in some peripheral tissues. The wide distribution of ghrelin
receptor and the number of tissues and cell types known to respond to ghrelin
suggest that a number of systems may be affected by treatment with this hormone
or its analogues. In this study, we characterized a new GHSR specific monoclonal
antibody recognizing specifically the ghrelin receptor. This could be a useful
tool for immunoassays aimed at obtaining insights into the physiological and
pathological significance of the GHSR/ghrelin system.
PMID- 28409696
TI - Collaborative Occupational Therapy: Teachers' Impressions of the Partnering for
Change (P4C) Model.
AB - AIMS: Occupational therapists (OTs) often face barriers when trying to
collaborate with teachers in school-based settings. Partnering for change (P4C),
a collaborative practice model designed to support children with developmental
coordination disorder, could potentially support all students with special needs.
Therefore, the aim of this study was to explore how teachers experience OT
services delivered using the P4C model to support children with a variety of
special needs. METHODS: P4C was implemented at one elementary school in
Courtenay, British Columbia. Eleven teachers participated in two focus groups and
a one-on-one interview to gather descriptive, qualitative data. Grounded theory
techniques were used for data analysis. RESULTS: Four themes (collaborating in
the thick of it all, learning and taking risks, managing limited time and
resources, and appreciating responsive OT support) represented teachers'
experiences of P4C. CONCLUSIONS: Teachers strongly preferred collaborative OT
services based on the P4C model. Students with a variety of special needs were
supported within their classrooms as teachers learned new strategies from the OT
and found ways to embed these strategies into their daily routines.
PMID- 28409697
TI - LGBT Rights Activism and Homophobia in Russia.
AB - This article explores how lesbian, gay, bisexual, and transgender/transsexual
(LGBT) people's perception of increasing conservative trends and negative public
attitudes affected the development of LGBT rights activism in Russia. It includes
following sections: (1) the analysis of the development of LGBT community and
activism in Russia; (2) the investigation of public perception of same-sex
relations and how LGBT people's views of it affected their readiness to join
activism; and (3) the examination of the state's policy toward LGBT people in a
wake of conservative discourse and its impact on LGBT activism and LGBT people's
willingness to get involved in it. The article concludes by considering
implications that LGBT rights activism face nowadays in order to survive and
continue its existence.
PMID- 28409698
TI - Less is more: does the addition of barrel staves improve results in endoscopic
strip craniectomy for sagittal craniosynostosis?
AB - OBJECTIVE Endoscopic strip craniectomy (ESC) with postoperative helmet orthosis
is a well-established treatment option for sagittal craniosynostosis. There are
many technical variations to the surgery ranging from simple strip craniectomy to
methods that employ multiple cranial osteotomies. The purpose of this study was
to determine whether the addition of lateral barrel-stave osteotomies during ESC
improved morphological outcomes. METHODS An IRB-approved retrospective review was
conducted on a consecutive series of cases involving ESC for sagittal
craniosynostosis at 2 different institutions from March 2008 to August 2014. The
patients in Group A underwent ESC and those in Group B had ESC with lateral
barrel-stave osteotomies. Demographic and perioperative data were recorded;
postoperative morphological outcomes were analyzed using 3D laser scan data
acquired from a single orthotic manufacturer who managed patients from both
institutions. RESULTS A total of 73 patients were included (34 in Group A and 39
in Group B). Compared with Group B patients, Group A patients had a shorter mean
anesthetic time (161.7 vs 195 minutes; p < 0.01) and operative time (71.6 vs 111
minutes; p < 0.01). The mean hospital stay was similar for the 2 groups (1.2 days
for Group A vs 1.4 days for Group B; p = 0.1). Adequate postoperative data on
morphological outcomes were reported by the orthotic manufacturer for 65 patients
(29 in Group A and 36 in Group B). The 2 groups had similar improvement in the
cephalic index (CI): Group A, mean change 10.5% (mean preoperative CI 72.6, final
80.4) at a mean follow-up of 13.2 months; Group B, mean change 12.2% (mean
preoperative CI 71.0, final 79.6) at a mean follow-up of 19.4 months. The
difference was not statistically significant (p = 0.15). CONCLUSIONS Both ESC
alone and ESC with barrel staving produced excellent outcomes. However, the
addition of barrel staves did not improve the results and, therefore, may not be
warranted in the endoscopic treatment of sagittal craniosynostosis.
PMID- 28409699
TI - Potential for Medicaid Savings: A State and National Comparison of an Innovative
Neonatal Abstinence Syndrome Treatment Model.
AB - In recent years, neonatal abstinence syndrome (NAS) rates have increased rapidly
across the United States, rising from 1.2 (2000) to 5.8 (2012) per 1000 hospital
births annually. Because most NAS infants are treated in an intensive care
setting, associated hospital charges are high and continue to escalate, rising on
average from $39,400 in 2000 to $66,700 in 2012. An innovative NAS treatment
program, which includes early-initiated methadone therapy, rooming-in, and
combined inpatient/outpatient weaning in a low-acuity nursery, has been in place
since 2003 at a large Southeastern hospital. The program has proven safe,
effective and low cost for treating infants of >=35 weeks gestational age whose
mothers used long-acting opioids. Given that 81% of NAS cases in the United
States are funded by Medicaid programs and that the cost burden is rising
rapidly, researchers considered the potential saved charges associated with
implementing the same program in other hospitals state- and nationwide.
Researchers used regression models to project state and national NAS birth rates
from 2015-2025 and to predict future NAS charges under current treatment
protocols. Three scenarios were developed to compare the potential saved charges
of implementing the innovative NAS treatment program across the state and nation
with assumptions related to the percent of NAS infants eligible for the program,
percent funded by Medicaid, and fluctuations in average length of stay. The
potential saved charges are substantial, creating a compelling case for policy
makers and hospitals in the pursuit of safe, effective, and cost-conscious NAS
care.
PMID- 28409700
TI - High-yield of biologically active recombinant human fibroblast growth factor-16
in E. coli and its mechanism of proliferation in NCL-H460 cells.
AB - Fibroblast growth factor-16 (FGF16) is a member of FGF9 subfamily, which plays
key role in promoting mitosis and cell survival, and also involved in embryonic
development, cell growth, tissue repair, morphogenesis, tumor growth, and
invasion. However, the successful high-yield purification of recombinant human
fibroblast growth factor-16 (rhFGF16) protein has not been reported. In addition,
lung cancer is a major cause of cancer-related deaths, which threats people's
lives and its incidence has continued to rise. Learning pathways or proteins,
which involved in lung tumor progression will contribute to the development of
early diagnosis and targeted therapy. FGF16 promoted proliferation and invasion
behavior of SKOV-3 ovarian cancer cells, whose function may be similar in lung
cancer. The hFGF16 was cloned into pET-3d and expressed in Escherichia coli BL21
(DE3) pLysS. Finally, obtained two forms of FGF16 that exhibited remarkable
biological activity and the purity is over 95%, meanwhile, the yield of soluble
130 mg/100 g and insoluble 240 mg/100 g. Experiments demonstrated FGF16 could
promote proliferation of NCL-H460 cells by activating Akt, Erk1/2, and p38 MAPK
signaling, whereas JNK had no significant effect. In total, this optimized
expression strategy enables significant quantity and activity of rhFGF16, thereby
meeting its further pharmacological and clinical usages.
PMID- 28409701
TI - A Road Map to Integrate Social Determinants of Health into Electronic Health
Records.
PMID- 28409702
TI - Providing Health Information to Latino Farmworkers: The Case of the Affordable
Care Act.
AB - OBJECTIVE: Providing health program information to vulnerable communities, such
as Latino farmworkers, is difficult. This analysis describes the manner in which
farmworkers receive information about the Affordable Care Act, comparing
farmworkers with other Latinos. METHODS: Interviews were conducted with 100
Latino farmworkers and 100 urban Latino North Carolina residents in 2015.
RESULTS: Most farmworkers had received health information from a community
organization. Trusted sources for health information were health care providers
and community organizations. Sources that would influence decisions to enroll
were Latino nurses and doctors, religious leaders, and family members.
Traditional media, including oral presentation and printed material at the
doctor's office, were preferred by the majority of farmworkers and non
farmworkers. Farmworkers used traditional electronic media: radio, television,
and telephone. More non-farmworkers used current electronic media: e-mail and
Internet. CONCLUSIONS: Latino farmworkers and non-farmworkers prefer traditional
media in the context of a health care setting. They are willing to try
contemporary electronic media for this information.
PMID- 28409704
TI - Attitudes Toward Homosexuality in Adolescence: An Italian Study.
AB - This study investigates Italian adolescents' attitudes toward gay men and
lesbians and same-sex marriage, and their beliefs about the origins of
homosexuality. The sample consists of 449 subjects (226 males), aged between 14
and 21 years. The principal instruments used are: the Attitudes Toward Lesbians
and Gay men (ATLG), the Modern Homonegativity Scale (MHS), and the Attitudes
Toward Same-Sex Marriage (ATSM). Results suggest that males show a more negative
attitude than females toward homosexuals. Furthermore data reveal that
respondents with a lack of personal direct contact with gay people have less
positive attitudes toward homosexual people and same-sex marriage. The data in
this study suggest that homophobia could be deeply rooted in a traditional value
system that refutes gender equality.
PMID- 28409705
TI - Letter from the editor.
PMID- 28409703
TI - Beyond Screening: A Stepped Care Pathway for Managing Postpartum Depression in
Pediatric Settings.
AB - The negative consequences of untreated postpartum depression (PD) for both the
woman and her infant are well established. The impact of maternal depression has
led to recommendations on systematic perinatal depression screening.
Unfortunately, large-scale initiatives on PD screening have found no benefit
unless systems are in place to facilitate appropriate interventions for women who
screen positive. Pediatric primary care has been a focus of efforts to support
screening and management of PD because pediatric providers, unlike adult
healthcare providers, have the most frequent contact with postpartum women
through well-child visits. Well-child visits thus present an unparalleled
opportunity to detect and intervene with PD. Literature reviews suggest that
specific strategies are feasible within pediatric settings and could benefit both
the woman and her child. In this article, we present a stepped care approach for
screening and managing PD, integrating common elements found in existing
pediatric-based models. A stepped care approach is ideal because PD is a
heterogeneous condition, with a range of presentations and hence responsiveness
to various interventions. This care pathway begins with systematic screening for
depression symptoms, followed by a systematic risk assessment for women who
screen positive and care management based on risk profiles and responsiveness.
This approach allows pediatric providers to be optimally flexible and responsive
in addressing the majority of women with PD within the context of the family
centered medical home to improve child well-being. Challenges to managing PD
within pediatrics are discussed, including strategies for addressing them.
Implications for research, policy, and practice are discussed.
PMID- 28409706
TI - Human Vaccines & Immunotherapeutics: News.
PMID- 28409707
TI - Corrigendum.
PMID- 28409708
TI - Engaging men and women in feminist health issues.
PMID- 28409709
TI - The lived experience of help-seeking by South African women after sexual assault.
AB - The purpose of this study was to explore the lived experience of help-seeking by
South African women following sexual assault. Hermeneutic phenomenology guided
the study. Interviews were conducted with six women who had experienced sexual
assault at some point in their lives. Three venues were most significant to
women's help-seeking experiences: the criminal justice system, health care
facilities, and/or social service agencies. Essentially, the women's help-seeking
experiences in these three venues are best described as fraught justice-seeking,
pragmatic help-seeking, and desperate help-seeking. The study findings have
implications for the provision of services for women who experience sexual
assault in South Africa.
PMID- 28409710
TI - Applying WHO's Age-Friendly Communities Framework to a National Survey in China.
AB - The World Health Organization (WHO)'s Age-Friendly Community (AFC) initiative has
gained worldwide momentum. Yet, measures have not been validated in regions with
various levels of socio-economic development. This article used a nationally
representative dataset in China to (a) analyze community-level measures within
the framework of AFC and (b) compare the age-friendliness between rural and urban
settings in China. Chi- square and t-tests examined the rural and urban
differences. Results suggest that many AFC concepts did not apply well in
developing areas. The Chinese survey measured important environmental aspects in
developing regions that were missing in the WHO AFC framework.
PMID- 28409711
TI - Silver Alerts: A Notification System for Communities with Missing Adults.
AB - As the U.S. population ages, the prevalence of dementia will grow and communities
will face the problem of older adults wandering or becoming lost. Silver Alert
systems are programs designed to locate missing older adults with dementia or
other mental disabilities. Such programs have been initiated in all but five
states. Data collection for these programs is often minimal or incomplete. Social
workers should be involved in prevention, follow up and education with
caregivers, community members and law enforcement officers. When reviewing Silver
Alert policy, special attention must be given to ethical concerns and protection
of older adults' civil rights.
PMID- 28409712
TI - Self-Disclosing Trauma and Post-Traumatic Stress Symptoms in Couples: A
Longitudinal Study.
AB - OBJECTIVE: Most research concerning the implications of self-disclosure on
trauma's aftermath has focused on the salubrious effects disclosure may foster
for the primary victim. However, the manner in which recipients of disclosure are
symptomatically affected by it remains unexamined. Of particular interest are
spouses who are often the primary support providers and are therefore susceptible
to secondary traumatization. Assessing posttraumatic stress symptoms (PTSS) and
self-disclosure among traumatized veterans and their wives, the current
longitudinal study begins to fill this gap in the literature. METHOD: A total of
220 couples consisting of Israeli veterans, of whom 128 were former prisoners of
war (ex-POWs) and 92 were combatants, and their wives were examined. PTSS and
self-disclosure of both partners were assessed 30 and 35 years after the war
using the Posttraumatic Stress Disorder Inventory (PTSD-I; Solomon et al., 1993)
and the Self-Disclosure Index (SDI; Miller, Berg, & Archer, 1983), respectively.
Analyses included Pearson intercorrelations analyses and four stepwise
hierarchical multiple regression analyses. RESULTS: Findings indicated that
increments in veterans' disclosure are not only consistently associated with the
reduction of their wives' PTSS but may also explain and predict some of the
change in the wives' PTSS over time. However, such a longitudinal effect was not
evident concerning the veterans' PTSS. CONCLUSION: Traumatized ex-POWs' and
combatants' self-disclosure within the marital relationship may contribute to the
amelioration of their wives' secondary traumatization, and thus may be a goal
worth pursuing in therapy. However, more research is needed to further understand
this relation.
PMID- 28409713
TI - Persistent Complex Bereavement Disorder and Culture: Early and Prolonged Grief in
Nepali Widows.
AB - OBJECTIVE: Persistent complex bereavement disorder (PCBD) in the Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has not been well
studied in socioculturally diverse populations. Thus, this qualitative study
examined (a) how widows in Nepal understand grief, (b) whether a local construct
of PCBD exists, and (c) its comparability with the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5), terminology. METHODS: Using an
adapted Explanatory Model Interview Catalogue (EMIC) framework, semistructured
interviews with 25 widows and 12 key informants, as well as three focus-group
discussions (n = 20), were conducted between October 2014 and April 2015. Through
an inductive grounded theory-based approach, we used the constant comparative
method, iteratively coding transcripts to identify themes and patterns in the
data. Also, we created two lists of grief responses, one of early reactions and
another all reactions to grief, based on the frequency of mention. RESULTS: No
single term for grief was reported. Widows reported a local construct of PCBD,
which was broadly compatible with DSM-5 terminology but with important variation
reflecting societal influence. Surviving torture during conflict, economic and
family stressors, and discrimination were mentioned as important determinants
that prolong and complicate grief. Suicidal ideation was common, with about 31%
and 62% of widows reporting past-year and lifetime suicidality, respectively.
Findings may not be generalizable to all Nepali widows; participants were
recruited from a non-governmental organization, from Kathmandu and its
neighboring districts, and were primarily of reproductive age. CONCLUSIONS: While
PCBD symptoms proposed in DSM-5 were mentioned as relevant by study participants,
some components may need adaptation for use in non-Western settings, such as
Nepal.
PMID- 28409714
TI - Psychotic Depression and Suicidal Behavior.
AB - OBJECTIVE: This study investigated how severely depressed individuals experienced
the relationship between psychotic symptoms and suicidal ideation and behavior.
METHOD: Semi-structured qualitative interviews were conducted with a purposive
sample of nine inpatients from a psychiatric university hospital between
September 2012 and May 2013 fulfilling diagnostic criteria for a psychotic
depressive episode as part of a unipolar or bipolar disorder. Analysis was
conducted using systematic text condensation. RESULTS: Participants experienced
(1) being directed to perform impulsive potentially fatal actions, (2) feeling
hounded to death, (3) becoming trapped in an inescapable darkness, and (4) being
left bereft of mental control. They described how impulsivity directed by
delusions and hallucinations resulted in unpredictable actions with only moments
from decision to conduct. Suicide was seen as an escape not only from life
problems but also from psychotic experiences and intense anxiety. Participants
reported being in a chaotic state, unable to think rationally or anticipate the
consequences of their actions. Their ability to identify and communicate
psychotic symptoms and suicidal ideation and behavior was compromised, leaving
them to struggle alone with these terrifying experiences. CONCLUSIONS: Suicide
risk assessments based on verbal reports from individuals with psychotic
depression may not always be valid due to potential impulsivity and
underreporting of suicidal ideation. It may be important for clinicians to
explore the delusional content of such patients' experiences to assess the
possibility of suicide as a result of shame, guilt, remorse, or altruistic
intentions to save others from harm.
PMID- 28409715
TI - An Open Effectiveness Trial of a Multimodal Inpatient Treatment for Depression
and Anxiety Among Adults With Serious Mental Illness.
AB - OBJECTIVE: This prospective open effectiveness trial examined symptom change
trajectories and rates of remission from depression and anxiety in an intensive
multimodal inpatient treatment for adults with serious mental illness (SMI).
Patient baseline characteristics were examined as mediators/moderators of
treatment response. METHODS: Adult inpatients with SMI (N = 994) completed an
average of 39 days of inpatient treatment. Latent growth curve (LGC) methods were
used to model symptom trajectories, estimating expected remission based on
individual patterns of change observed across the sample. RESULTS: Absolute
reductions in symptoms were substantial, with large effect size improvements for
both depression (d = 1.21, 95% CI [1.13, 1.29]) and anxiety (d = 1.13, 95% CI
[1.05, 1.21]). For those presenting with elevated depressive symptoms (Patient
Health Questionnaire-Depression >= 5.0; 87.5% of the sample), 46.9% evidenced
remission from admission to discharge. Among patients presenting with significant
anxiety (Patient Health Questionnaire-Generalized Anxiety Disorder Screener >=
5.0; 84.5% of the sample), 50.0% evidenced remission from admission to discharge.
Mediation analyses revealed that depression and anxiety severity decreased more
rapidly with increasing age and initial levels of experiential avoidance.
CONCLUSIONS: Rates of remission of depression and anxiety were greater than
anticipated in this large cohort of adult SMI inpatients and may be related to
intensity and length of hospitalization.
PMID- 28409716
TI - Gang Membership: Links to Violence Exposure, Paranoia, PTSD, Anxiety, and Forced
Control of Behavior in Prison.
AB - OBJECTIVE: Gang membership inherently links to violence, and violent experiences
strongly relate to posttraumatic stress disorder (PTSD), anxiety, and paranoia.
Yet to date, gang members' mental health has received little attention, and their
paranoia has not been examined. This study, using established measures, assessed
street gang and nongang prisoners' levels of violence exposure, symptoms of PTSD,
paranoia, and anxiety, forced behavioral control, and segregation in prison.
METHOD: Participants were 65 (32 gang and 33 nongang) prisoners, recruited using
opportunity sampling. Participants provided informed consent and were interviewed
individually. Interviews were anonymized to maintain confidentiality. Chi-square
and discriminant function analyses were used to compare participants'
demographics, segregation levels, mental health symptoms, and to identify
predictors of street gang membership. RESULTS: As compared to nongang prisoners,
street gang prisoners have higher levels of exposure to violence, symptoms of
paranoia, PTSD, anxiety, and forced control of their behavior in prison. Street
gang prisoners were not more likely to be segregated, but they were more likely
to belong to ethnic minorities. Street gang prisoners were only found to be
younger than nongang prisoners, when other variables were controlled for.
CONCLUSIONS: Mental health deserves more attention in gang research. The
implications of findings are that gang membership may undermine members' mental
health, and/or that individuals with existing mental health problems may be those
attracted to gang membership. Moreover, justice responses, via policies and
intervention strategies, need to identify and address the mental health needs in
gang member prisoners, if successful rehabilitation of gang members is to be
achieved.
PMID- 28409717
TI - Being in Dangerous Territory: Ethical Decision Making and Boundary Negotiations.
PMID- 28409718
TI - Older Adults Exposed to Ongoing versus Intense Time-Limited Missile Attacks:
Differences in Symptoms of Posttraumatic Stress Disorder.
AB - OBJECTIVE: The potentially different psychological effects of ongoing trauma vis
a-vis an intense time-limited exposure to trauma have not been examined in older
adults. Therefore, this study examined posttraumatic stress disorder (PTSD)
symptoms and their health concomitants in two groups of older adults in Israel:
those exposed to ongoing missile attacks and those exposed to an intense time
limited period of missile attacks. METHOD: In the third administration of the
Israeli component of the Survey of Health, Ageing, and Retirement in Europe
(SHARE-Israel), 297 older adults reported ongoing exposure to missile attacks due
to the Israel-Gaza conflict (mean age = 66.97), while 309 older adults reported
exposure to an intense period of missile attacks during the Second Lebanon War
(mean age = 66.63). Participants completed measures of PTSD symptoms, and
physical, cognitive, and mental health. RESULTS: Older adults with ongoing
exposure reported higher PTSD symptom level relative to those with intense time
limited exposure. The groups also differed in health variables related to PTSD
symptoms. Namely, impaired physical and cognitive health were related to a higher
level of PTSD symptoms in ongoing exposure, while impaired mental health was
related to a higher PTSD symptom level following intense time-limited exposure.
CONCLUSIONS: The findings suggest that physical and cognitive health involves
resources that are vital for daily survival when living under ongoing warfare
threat, whereas mental health involves resources that are needed in dealing with
psychological effects of warfare trauma. Accordingly, different interventions may
be necessary when helping older adults exposed to ongoing versus intense time
limited trauma.
PMID- 28409720
TI - Rejection Sensitivity and Depression: Indirect Effects Through Problem Solving.
AB - OBJECTIVE: Rejection sensitivity (RS) and deficits in social problem solving are
risk factors for depression. Despite their relationship to depression and the
potential connection between them, no studies have examined RS and social problem
solving together in the context of depression. As such, we examined RS, five
facets of social problem solving, and symptoms of depression in a young adult
sample. METHOD: A total of 180 participants completed measures of RS, social
problem solving, and depressive symptoms. We used bootstrapping to examine the
indirect effect of RS on depressive symptoms through problem solving. RESULTS: RS
was positively associated with depressive symptoms. A negative problem
orientation, impulsive/careless style, and avoidance style of social problem
solving were positively associated with depressive symptoms, and a positive
problem orientation was negatively associated with depressive symptoms. RS
demonstrated an indirect effect on depressive symptoms through two social problem
solving facets: the tendency to view problems as threats to one's well-being and
an avoidance problem-solving style characterized by procrastination, passivity,
or overdependence on others. CONCLUSIONS: These results are consistent with prior
research that found a positive association between RS and depression symptoms,
but this is the first study to implicate specific problem-solving deficits in the
relationship between RS and depression. Our results suggest that depressive
symptoms in high RS individuals may result from viewing problems as threats and
taking an avoidant, rather than proactive, approach to dealing with problems.
These findings may have implications for problem-solving interventions for
rejection sensitive individuals.
PMID- 28409721
TI - Ethics, Risk Management, and an Intersectional View of LGBT Mental Health.
PMID- 28409722
TI - Complete endoscopic resection of a pituitary stalk epidermoid cyst using a
combined infrasellar interpituitary and suprasellar endonasal approach: case
report.
AB - Intracranial epidermoid cysts are benign lesions of epithelial origin that most
frequently present with symptoms of mass effect. Although they are often
associated with a high rate of residual tumor and recurrence, maximal safe
resection usually leads to good outcomes. The authors report a complete resection
of an uncommon pituitary stalk epidermoid cyst with intrasellar extension using a
combined suprasellar and infrasellar interpituitary, endoscopic endonasal
transsphenoidal approach. The patient, a 54-year-old woman, presented with
headache, visual disturbance, and diabetes insipidus. Postoperatively, she
reported improvement in her visual symptoms and well-controlled diabetes
insipidus using 0.1 mg of desmopressin at bedtime and normal anterior pituitary
gland function. One year later, she continues to receive the same dosage of
desmopressin and is also taking 50 mcg of levothyroxine daily after developing
primary hypothyroidism unrelated to the surgical procedure. A combined
infrasellar interpituitary and suprasellar approach to this rare location for an
epidermoid cyst can lead to a safe and complete resection with good clinical
outcomes.
PMID- 28409723
TI - Role of electrophysiology in guiding near-total resection for preservation of
facial nerve function in the surgical treatment of large vestibular schwannomas.
AB - OBJECTIVE In large vestibular schwannoma (VS) surgery, the facial nerve (FN) is
at high risk of injury. Near-total resection has been advocated in the case of
difficult facial nerve dissection, but the amount of residual tumor that should
be left and when dissection should be stopped remain controversial factors. The
objective of this study was to report FN outcome and radiological results in
patients undergoing near-total VS resection guided by electromyographic
supramaximal stimulation of the FN at the brainstem. METHODS This study was a
retrospective analysis of a prospectively maintained database. Inclusion criteria
were surgical treatment of a large VS during 2014, normal preoperative FN
function, and an incomplete resection due to the strong adherence of the tumor to
the FN and the loss of around 50% of the response of supramaximal stimulation of
the proximal FN at 2 mA. Facial nerve function and the amount and evolution of
the residual tumor were evaluated by clinical examination and by MRI at a mean of
5 days postoperatively and at 1 year postoperatively. RESULTS Twenty-five
patients met the inclusion criteria and were included in the study. Good FN
function (Grade I or II) was observed in 16 (64%) and 21 (84%) of the 25 patients
at Day 8 and at 1 year postoperatively, respectively. At the 1-year follow-up
evaluation (n = 23), 15 patients (65%) did not show growth of the residual tumor,
6 patients (26%) had regression of the residual tumor, and only 2 patients (9%)
presented with tumor progression. CONCLUSIONS Near-total resection guided by
electrophysiology represents a safe option in cases of difficult dissection of
the facial nerve from the tumor. This seems to offer a good compromise between
the goals of preserving facial nerve function and achieving maximum safe
resection.
PMID- 28409724
TI - Letter to the Editor. Seasonal subarachnoid hemorrhage: temperature or daylight?
PMID- 28409725
TI - Genetic landscape of sporadic vestibular schwannoma.
AB - OBJECTIVE Vestibular schwannoma (VS) is a benign tumor with associated
morbidities and reduced quality of life. Except for mutations in NF2, the genetic
landscape of VS remains to be elucidated. Little is known about the effect of
Gamma Knife radiosurgery (GKRS) on the VS genome. The aim of this study was to
characterize mutations occurring in this tumor to identify new genes and
signaling pathways important for the development of VS. In addition, the authors
sought to evaluate whether GKRS resulted in an increase in the number of
mutations. METHODS Forty-six sporadic VSs, including 8 GKRS-treated tumors and
corresponding blood samples, were subjected to whole-exome sequencing and tumor
specific DNA variants were called. Pathway analysis was performed using the
Ingenuity Pathway Analysis software. In addition, multiplex ligation-dependent
probe amplification was performed to characterize copy number variations in the
NF2 gene, and microsatellite instability testing was done to investigate for DNA
replication error. RESULTS With the exception of a single sample with an
aggressive phenotype that harbored a large number of mutations, most samples
showed a relatively low number of mutations. A median of 14 tumor-specific
mutations in each sample were identified. The GKRS-treated tumors harbored no
more mutations than the rest of the group. A clustering of mutations in the
cancer-related axonal guidance pathway was identified (25 patients), as well as
mutations in the CDC27 (5 patients) and USP8 (3 patients) genes. Thirty-five
tumors harbored mutations in NF2 and 16 tumors had 2 mutational hits. The samples
without detectable NF2 mutations harbored mutations in genes that could be linked
to NF2 or to NF2-related functions. None of the tumors showed microsatellite
instability. CONCLUSIONS The genetic landscape of VS seems to be quite
heterogeneous; however, most samples had mutations in NF2 or in genes that could
be linked to NF2. The results of this study do not link GKRS to an increased
number of mutations.
PMID- 28409726
TI - The suboccipital ligament.
AB - OBJECTIVE A fibrous structure located dorsal to the dura at the posterior
craniocervical junction stretches horizontally between the bilateral occipital
condyles and the upper borders of the C-1 laminae. Partially covered by the
occipital bone, this structure is always encountered when the bone is removed
from the foramen magnum rim during approaches to the posterior cranial fossa.
Although known to surgeons, this structure has not been defined, studied, or
named. The most appropriate name for this structure is "the suboccipital
ligament," and a detailed rationale for this name is provided. METHODS This 3
year-long study included 10 cadaveric specimens and 39 clinical patients: 31
consecutive surgically treated patients with Chiari Type I malformations (CM-I
subgroup) and 8 other patients with posterior fossa pathologies (non-CM-I
subgroup). The dimensions were defined, the function of this ligament was
hypothesized, size and histological composition were compared between patient
subgroups, and its origin and relationship to the surrounding structures were
analyzed. Possible statistical differences in the parameters between the 2 groups
were also evaluated. RESULTS The suboccipital ligament consists of horizontally
oriented hyaline fibers and has a median length of 35 mm, height of 10 mm, and
thickness of 0.5 mm. These dimensions are not significantly different between the
CM-I and non-CM-I patients. The median age of the patients was 43 years, with CM
I patients being significantly younger (median 35 years) than non-CM-I patients
(median 57 years). There was no statistically significant difference in weight,
height, and body mass index between patient subgroups. There was no significant
correlation between the body mass index or height of the patients and the
dimensions of the ligament. No statistically significant differences existed
between the subgroups in terms of smoking history, alcohol consumption, and the
presence of diabetes mellitus, hypertension, hydrocephalus, or headaches. The
ligament tissue in the CM-I patients was disorganized with poorly arranged
collagen bands and interspersed adipose tissue. These patients also had more
hyalinized fibrosis and showed changes in the direction of fibers, with hyaline
nodules ranging from 0 to 2+. The result of the histological evaluation of the
suboccipital ligament for hyaline nodules, calcification, and ossification was
graded as 2+ if present in 3 or more medium-power magnification fields (MPFs); 1+
if present in 1-2 MPFs; and 0, if present in less than 1 MPF. Histological
examination of the ligaments showed structural differences between CM-I and non
CM-I patients, most notably the presence of hyaline nodules and an altered fiber
orientation in CM-I patients. CONCLUSIONS The suboccipital ligament extends
between the occipital condyle and the superior edge of the C-1 lamina, connecting
the contralateral sides, and appears to function as a real ligament. It is
ventral to the occipital bone, which covers approximately two-thirds of the
height of the ligament and is loosely attached to the dura medially and more
firmly laterally. Because of its distinctive anatomy, characteristics, and
function, the suboccipital ligament deserves its own uniform designation and
name.
PMID- 28409727
TI - Clival chordomas: considerations after 16 years of endoscopic endonasal surgery.
AB - OBJECTIVE In the past decade, the role of the endoscopic endonasal approach (EEA)
has relevantly evolved for skull base tumors. In this study, the authors review
their surgical experience with using an EEA in the treatment of clival chordomas,
which are deep and infiltrative skull base lesions, and they highlight the
advantages and limitations of this ventral approach. METHODS All consecutive
cases of chordoma treated with an EEA between 1998 and 2015 at a single
institution are included in this study. Preoperative assessment consisted of
neuroimaging (MRI and CT with angiography sequences) and endocrinological,
neurological, and ophthalmological evaluations, which were repeated 3 months
after surgery and annually thereafter. Postoperative adjuvant therapies were
considered. RESULTS Sixty-five patients (male/female ratio 1:0.9) were included
in this study. The median age was 48 years (range 9-80 years). Gross-total
resection (GTR) was achieved in 47 cases (58.7%). On univariate analysis, primary
procedures (p = 0.001), location in the superior or middle third of the clivus (p
= 0.043), extradural location (p = 0.035), and histology of conventional
chordomas (p = 0.013) were associated with a higher rate of GTR. The complication
rate was 15.1%, and there were no perioperative deaths. Most complications did
not result in permanent sequelae and included 2 CSF leaks (2.5%), 5 transient
cranial nerve VI palsies (6.2%), and 2 internal carotid artery injuries (2.5%),
which were treated with coil occlusion of the internal carotid artery without
neurological deficits. Three patients (3.8%) presented with complications
resulting in permanent neurological deficits due to a postoperative hematoma
(1.2%) causing a hemiparesis, and 2 permanent ophthalmoplegias (2.5%). Seventeen
patients (26.2%) have died of tumor progression over the course of follow-up
(median 52 months, range 7-159 months). Based on Kaplan-Meier analysis, the
survival rate was 77% at 5 years and 57% at 10 years. On multivariate analysis,
the extent of tumor removal (p = 0.001) and the absence of previous treatments (p
= 0.001) proved to be correlated with a longer survival rate. CONCLUSIONS The EEA
was associated with a high rate of tumor removal and symptom control, with low
morbidity and preservation of a good quality of life. These results allow for a
satisfactory overall survival rate, particularly after GTR and for primary
surgery. Considering these results, the authors believe that an EEA can be a
helpful tool in chordoma surgery, achieving a good balance between as much tumor
removal as possible and the preservation of an acceptable patient quality of
life.
PMID- 28409728
TI - Intracranial pressure in patients undergoing decompressive craniectomy: new
perspective on thresholds.
AB - OBJECTIVE Decompressive craniectomy (DC) is an established part of treatment in
patients suffering from malignant infarction of the middle cerebral artery (MCA)
or traumatic brain injury (TBI). However, no clear evidence for intracranial
pressure (ICP)-guided therapy after DC exists. The lack of this evidence might be
due to the frequently used, but simplified threshold for ICP of 20 mm Hg, which
determines further therapy. Therefore, the objective of this study was to
evaluate this threshold's accuracy and to investigate the course of ICP values
with respect to neurological outcome. METHODS Data on clinical characteristics
and parameters of the ICP course on the intensive care unit were collected
retrospectively in 102 patients who underwent DC between December 2007 and April
2014 at the authors' institution. The postoperative ICP course in the first 168
hours was recorded and analyzed. From these findings, ICP thresholds
discriminating favorable from unfavorable outcome were calculated using
conditional inference tree analysis. Additionally, survival analysis was
performed using the Kaplan-Meier method. Prognostic factors were assessed via
univariate analysis and multivariate logistic regression. Favorable outcome was
defined as a score of 0-4 on the modified Rankin Scale. RESULTS Multivariate
logistic regression revealed that anisocoria, diagnosis, and ICP values differed
significantly between the outcome groups. ICP values in the favorable and
unfavorable outcome groups differed significantly (p < 0.001), while the mean ICP
of both groups lay below the limit of 20 mm Hg (17.5 and 11.5 mm Hg,
respectively). These findings were reproduced when analyzing the underlying
pathologies of TBI and MCA infarction separately. Based on these findings,
optimized time-dependent threshold values were calculated and found to be between
10 and 17 mm Hg. These values significantly distinguished favorable from
unfavorable outcome and predicted 30-day mortality (p < 0.001). CONCLUSIONS This
study systematically evaluated ICP levels in a long-term analysis after DC and
provides new, surprisingly low, time-dependent ICP thresholds for these patients.
Future trials investigating the benefit of ICP-guided therapy should take these
thresholds into consideration and validate them in further patient cohorts.
PMID- 28409729
TI - Neuropsychological function after endovascular and neurosurgical treatment of
subarachnoid hemorrhage: a systematic review and meta-analysis.
AB - OBJECTIVE Subarachnoid hemorrhage (SAH) is treated with either surgical clipping
or endovascular coiling, though the latter is the preferred treatment method
given its more favorable functional outcomes. However, neuropsychological
functioning after treatment is rarely taken into account. In this meta-analysis,
the authors synthesized relevant data from the literature and compared
neuropsychological functioning in patients after coiling and clipping of SAH.
They hypothesized that the coiled patients would outperform the clipped patients;
that group differences would be greater with higher posterior circulation rupture
rates, in older patients, and in more recent publications; that group differences
would be smaller with greater rates of middle cerebral artery (MCA) rupture; and
that anterior communicating artery (ACoA) rupture rates would not influence
effect sizes. METHODS The MEDLINE, Embase, and PsycINFO databases were searched
for clinical studies that compared neuropsychological functioning after either
endovascular coiling or surgical clipping for SAH. Hedge's g and 95% confidence
intervals were calculated using random effects models. Patients who had undergone
coiling or clipping were compared on test performance in 8 neuropsychological
domains: executive functions, language, attention/processing speed, verbal
memory, visual memory, spatial memory, visuospatial functions, and intelligence.
Patients were also compared with healthy controls, and meta-regressions were used
to explore the relation between effect sizes and publication year, delay between
treatment and neuropsychological testing, mean patient age, and rates of
posterior circulation, ACoA, and MCA ruptures. RESULTS Thirteen studies with 396
clipped cases, 314 coiled cases, and 169 healthy controls were included in the
study. The coil-treated patients outperformed the clip-treated patients on
executive function (g = 0.17, 95% CI 0.08-0.25) and language tests (g = 0.23, 95%
CI 0.07-0.39), and all patients were impaired relative to healthy controls (g
ranged from -0.93 to -0.29). Coiled patients outperformed clipped patients to a
greater degree in more recent publications, over longer posttreatment testing
delays, and among older patients. Higher rates of posterior circulation and MCA
aneurysms were associated with smaller group differences, while ACoA rupture
rates did not influence effect sizes. CONCLUSIONS Coiling of SAH may promote
superior neuropsychological functioning under certain circumstances and could
have applications for the specialized care of SAH patients.
PMID- 28409731
TI - A direct aspiration first-pass technique vs stentriever thrombectomy in emergent
large vessel intracranial occlusions.
AB - OBJECTIVE Endovascular thrombectomy in patients with acute ischemic stroke caused
by occlusion of the proximal anterior circulation arteries is superior to
standard medical therapy. Stentriever thrombectomy with or without aspiration
assistance was the predominant technique used in the 5 randomized controlled
trials that demonstrated the superiority of endovascular thrombectomy. Other
studies have highlighted the efficacy of a direct aspiration first-pass technique
(ADAPT). METHODS To compare the angiographic and clinical outcomes of ADAPT
versus stentriever thrombectomy in patients with emergent large vessel occlusions
(ELVO) of the anterior intracranial circulation, the records of 134 patients who
were treated between June 2012 and October 2015 were reviewed. RESULTS Within
this cohort, 117 patients were eligible for evaluation. ADAPT was used in 47
patients, 20 (42.5%) of whom required rescue stentriever thrombectomy, and
primary stentriever thrombectomy was performed in 70 patients. Patients in the
ADAPT group were slightly younger than those in the stentriever group (63.5 vs
69.4 years; p = 0.04); however, there were no differences in the other baseline
clinical or radiographic factors. Procedural time (54.0 vs 77.1 minutes; p <
0.01) and time to a Thrombolysis in Cerebral Infarction (TICI) scale score of
2b/3 recanalization (294.3 vs 346.7 minutes; p < 0.01) were significantly lower
in patients undergoing ADAPT versus stentriever thrombectomy. The rates of TICI
2b/3 recanalization were similar between the ADAPT and stentriever groups (82.9%
vs 71.4%; p = 0.19). There were no differences in the rates of symptomatic
intracranial hemorrhage or procedural complications. The rates of good functional
outcome (modified Rankin Scale Score 0-2) at 90 days were similar between the
ADAPT and stentriever groups (48.9% vs 41.4%; p = 0.45), even when accounting for
the subset of patients in the ADAPT group who required rescue stentriever
thrombectomy. CONCLUSIONS The present study demonstrates that ADAPT and primary
stentriever thrombectomy for acute ischemic stroke due to ELVO are equivalent
with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores.
Given the reduced procedural time and time to TICI 2b/3 recanalization with
similar functional outcomes, an initial attempt at recanalization with ADAPT may
be warranted prior to stentriever thrombectomy.
PMID- 28409732
TI - The surgical treatment of tumors of the fourth ventricle: a single-institution
experience.
AB - OBJECTIVE Fourth ventricle tumors are rare, and surgical series are typically
small, comprising a single pathology, or focused exclusively on pediatric
populations. This study investigated surgical outcome and complications following
fourth ventricle tumor resection in a diverse patient population. This is the
largest cohort of fourth ventricle tumors described in the literature to date.
METHODS This is an 18-year (1993-2010) retrospective review of 55 cases involving
patients undergoing surgery for tumors of the fourth ventricle. Data included
patient demographic characteristics, pathological and radiographic tumor
characteristics, and surgical factors (approach, surgical adjuncts, extent of
resection, etc.). The neurological and medical complications following resection
were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were
reviewed to determine patient recovery. Patient, tumor, and surgical factors were
analyzed to determine factors associated with the frequently encountered
postoperative neurological complications. RESULTS There were no postoperative
deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of
patients experienced at least 1 major neurological complication, while 31% had
minor complications only. New or worsening gait/focal motor disturbance (56%),
speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most
common neurological deficits in the immediate postoperative period. Of these,
cranial nerve deficits were the least likely to resolve at follow-up.
Multivariate analysis showed that patients undergoing a transvermian approach had
a higher incidence of postoperative cranial nerve deficits, gait disturbance, and
speech/swallowing deficits than those treated with a telovelar approach. The use
of surgical adjuncts (intraoperative navigation, neurophysiological monitoring)
did not significantly affect neurological outcome. Twenty-two percent of patients
required postoperative CSF diversion following tumor resection. Patients who
required intraoperative ventriculostomy, those undergoing a transvermian
approach, and pediatric patients (< 18 years old) were all more likely to require
postoperative CSF diversion. Twenty percent of patients suffered at least 1
medical complication following tumor resection. Most complications were
respiratory, with the most common being postoperative respiratory failure (14%),
followed by pneumonia (13%). CONCLUSIONS The occurrence of complications after
fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae
were frequent, but a substantial number of patients had neurological improvement
at long-term followup. Of the neurological complications analyzed, postoperative
cranial nerve deficits were the least likely to completely resolve at follow-up.
Of all the patient, tumor, and surgical variables included in the analysis,
surgical approach had the most significant impact on neurological morbidity, with
the telovelar approach being associated with less morbidity.
PMID- 28409730
TI - Chronic multisite brain recordings from a totally implantable bidirectional
neural interface: experience in 5 patients with Parkinson's disease.
AB - OBJECTIVE Dysfunction of distributed neural networks underlies many brain
disorders. The development of neuromodulation therapies depends on a better
understanding of these networks. Invasive human brain recordings have a favorable
temporal and spatial resolution for the analysis of network phenomena but have
generally been limited to acute intraoperative recording or short-term recording
through temporarily externalized leads. Here, the authors describe their initial
experience with an investigational, first-generation, totally implantable,
bidirectional neural interface that allows both continuous therapeutic
stimulation and recording of field potentials at multiple sites in a neural
network. METHODS Under a physician-sponsored US Food and Drug Administration
investigational device exemption, 5 patients with Parkinson's disease were
implanted with the Activa PC+S system (Medtronic Inc.). The device was attached
to a quadripolar lead placed in the subdural space over motor cortex, for
electrocorticography potential recordings, and to a quadripolar lead in the
subthalamic nucleus (STN), for both therapeutic stimulation and recording of
local field potentials. Recordings from the brain of each patient were performed
at multiple time points over a 1-year period. RESULTS There were no serious
surgical complications or interruptions in deep brain stimulation therapy.
Signals in both the cortex and the STN were relatively stable over time, despite
a gradual increase in electrode impedance. Canonical movement-related changes in
specific frequency bands in the motor cortex were identified in most but not all
recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in
humans is feasible. The device performance characteristics described here may
inform the design of the next generation of totally implantable neural
interfaces. This research tool provides a platform for translating discoveries in
brain network dynamics to improved neurostimulation paradigms. Clinical trial
registration no.: NCT01934296 (clinicaltrials.gov).
PMID- 28409733
TI - Endovascular management of acute epidural hematomas: clinical experience with 80
cases.
AB - OBJECTIVE Small acute epidural hematomas (EDHs) treated conservatively carry a
nonmeasurable risk of late enlargement due to middle meningeal artery (MMA)
lesions. Patients with EDHs need to stay hospitalized for several days, with
neurological supervision and repeated CT scans. In this study, the authors
analyzed the safety and efficacy of the embolization of the involved MMA and
associated lesions. METHODS The study group consisted of 80 consecutive patients
harboring small- to medium-sized EDHs treated by MMA embolization between January
2010 and December 2014. A literature review cohort was used as a control group.
RESULTS The causes of head injury were falls, traffic-related accidents
(including car, motorcycle, and pedestrian vs vehicle accidents), and assaults.
The EDH topography was mainly temporal (lateral or pole). Active contrast leaking
from the MMA was seen in 57.5%; arteriovenous fistulas between the MMA and
diploic veins were seen in 10%; and MMA pseudoaneurysms were found in 13.6% of
the cases. Embolizations were performed under local anesthesia in 80% of the
cases, with N-butyl-2-cyanoacrylate, polyvinyl alcohol particles, or gelatin
sponge (or a combination of these), obtaining MMA occlusion and complete
resolution of the vascular lesions. All patients underwent follow-up CT scans
between 1 and 7 days after the embolization. In the 80 cases in this series, no
increase in size of the EDH was observed and the clinical evolution was
uneventful, without Glasgow Coma Scale score modification after embolization and
with no need for surgical evacuation. In contrast, the control cohort from the
literature consisted of 471 patients, 82 (17.4%) of whom shifted from
conservative treatment to surgical evacuation. CONCLUSIONS This study suggests
that MMA embolization is a highly effective and safe method to achieve size
stabilization in nonsurgically treated acute EDHs.
PMID- 28409734
TI - Intratumoral delivery of bortezomib: impact on survival in an intracranial glioma
tumor model.
AB - OBJECTIVE Glioblastoma (GBM) is the most prevalent and the most aggressive of
primary brain tumors. There is currently no effective treatment for this tumor.
The proteasome inhibitor bortezomib is effective for a variety of tumors, but not
for GBM. The authors' goal was to demonstrate that bortezomib can be effective in
the orthotopic GBM murine model if the appropriate method of drug delivery is
used. In this study the Alzet mini-osmotic pump was used to bring the drug
directly to the tumor in the brain, circumventing the blood-brain barrier; thus
making bortezomib an effective treatment for GBM. METHODS The 2 human glioma cell
lines, U87 and U251, were labeled with luciferase and used in the subcutaneous
and intracranial in vivo tumor models. Glioma cells were implanted subcutaneously
into the right flank, or intracranially into the frontal cortex of athymic nude
mice. Mice bearing intracranial glioma tumors were implanted with an Alzet mini
osmotic pump containing different doses of bortezomib. The Alzet pumps were
introduced directly into the tumor bed in the brain. Survival was documented for
mice with intracranial tumors. RESULTS Glioma cells were sensitive to bortezomib
at nanomolar quantities in vitro. In the subcutaneous in vivo xenograft tumor
model, bortezomib given intravenously was effective in reducing tumor
progression. However, in the intracranial glioma model, bortezomib given
systemically did not affect survival. By sharp contrast, animals treated with
bortezomib intracranially at the tumor site exhibited significantly increased
survival. CONCLUSIONS Bypassing the blood-brain barrier by using the osmotic pump
resulted in an increase in the efficacy of bortezomib for the treatment of
intracranial tumors. Thus, the intratumoral administration of bortezomib into the
cranial cavity is an effective approach for glioma therapy.
PMID- 28409735
TI - Quantitative magnetic resonance angiography as a potential predictor for cerebral
hyperperfusion syndrome: a preliminary study.
AB - OBJECTIVE Cerebral hyperperfusion syndrome (CHS) is a rare but devastating
complication of carotid endarterectomy (CEA). This study sought to determine
whether quantitative hemodynamic assessment using MR angiography can stratify CHS
risk. METHODS In this prospective trial, patients with internal carotid artery
(ICA) stenosis were randomly selected for pre- and postoperative quantitative
phase-contrast MR angiography (QMRA). Assessment was standardized according to a
protocol and included Doppler/duplex sonography, MRI, and/or CT angiography and
QMRA of the intra- and extracranial supplying arteries of the brain. Clinical and
radiological data were analyzed to identify CHS risk factors. RESULTS Twenty-five
of 153 patients who underwent CEA for ICA stenosis were randomly selected for pre
and postoperative QMRA. QMRA data showed a 2.2-fold postoperative increase in
blood flow in the operated ICA (p < 0.001) and a 1.3-fold increase in the
ipsilateral middle cerebral artery (MCA) (p = 0.01). Four patients had clinically
manifested CHS. The mean flow increases in the patients with CHS were
significantly higher than in the patients without CHS, both in the ICA and MCA (p
< 0.001). Female sex and a low preoperative diastolic blood pressure were the
clearest clinical risk factors for CHS, whereas the flow differences and absolute
postoperative flow values in the ipsilateral ICA and MCA were identified as
potential radiological predictors for CHS. CONCLUSIONS Cerebral blood flow in the
ipsilateral ICA and MCA as assessed by QMRA significantly increased after CEA.
Higher mean flow differences in ICA and MCA were associated with the development
of CHS. QMRA might have the potential to become a noninvasive, operator
independent screening tool for identifying patients at risk for CHS.
PMID- 28409736
TI - Angiographic features of hemorrhagic moyamoya disease with high recurrence risk:
a supplementary analysis of the Japan Adult Moyamoya Trial.
AB - OBJECTIVE In this paper, the authors set out to identify the angiographic
features of moyamoya disease with posterior hemorrhage, which is a strong
predictor of rebleeding. METHODS This cross-sectional study used the data set of
the Japan Adult Moyamoya Trial (clinical trial registration no.: C000000166 [
www.umin.ac.jp/ctr/index.htm ]). The panel designed the ancillary measurement of
angiography at onset, classifying the collateral vessels into 3 subtypes:
lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis.
The association between each collateral and the hemorrhage site (anterior vs
posterior) was assessed in the hemorrhagic hemisphere by using multivariate
adjustment for potential confounders, including age, sex, and involvement of the
posterior cerebral artery (PCA). The association was confirmed through
topographical analysis of bleeding points. RESULTS Among the 80 participants, 75
hemorrhagic hemispheres of 75 patients were analyzed. Lenticulostriate
anastomosis was detected in 21 (28.0%) hemorrhagic hemispheres, thalamic
anastomosis in 22 (29.3%), and choroidal anastomosis in 35 (46.7%). Choroidal
anastomosis was a factor associated with posterior hemorrhage (OR 2.77 [95% CI
1.08-7.10], p = 0.034) and remained statistically significant after the
multivariate adjustment (OR 2.66 [95% CI 1.00-7.07], p = 0.049). PCA involvement
was also associated with posterior hemorrhage in both univariate and multivariate
analyses. Topographical analysis revealed good correspondence between bleeding
points associated with positive choroidal anastomosis and the anatomical
distribution of the choroidal arteries, including the thalamus and the wall of
the atrium. CONCLUSIONS Choroidal anastomosis and PCA involvement are
characteristic of posterior hemorrhage in moyamoya disease. Choroidal anastomosis
might be considered a potential source of posterior hemorrhage at high risk of
rebleeding.
PMID- 28409738
TI - President's message: The beast.
PMID- 28409739
TI - Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W
Meningococcal Disease, England, 2015-2016.
AB - During the first 12 months of an emergency meningococcal ACWY vaccination program
for teenagers in England, coverage among persons who left school in 2015, the
first cohort to be vaccinated, was 36.6%. There were 69% fewer group W
meningococcal cases than predicted by trend analysis and no cases in vaccinated
teenagers.
PMID- 28409740
TI - Quit Methods Used by US Adult Cigarette Smokers, 2014-2016.
AB - To quantify the prevalence of 10 quit methods commonly used by adult cigarette
smokers, we used data from a nationally representative longitudinal (2014-2016)
online survey of US adult cigarette smokers (n = 15,943). Overall, 74.7% of adult
current cigarette smokers used multiple quit methods during their most recent
quit attempt. Giving up cigarettes all at once (65.3%) and reducing the number of
cigarettes smoked (62.0%) were the most prevalent methods. Substituting some
cigarettes with e-cigarettes was used by a greater percentage of smokers than the
nicotine patch, nicotine gum, or other cessation aids approved by the US Food and
Drug Administration. Further research into the effectiveness of e-cigarettes as a
cessation aid is warranted.
PMID- 28409742
TI - Erratum, Vol. 13, April 28 Release.
AB - [This corrects the article DOI: 10.5888/pcd13.150500.].
PMID- 28409741
TI - Impact of Comorbidities Among Medicaid Enrollees With Chronic Obstructive
Pulmonary Disease, United States, 2009.
AB - INTRODUCTION: Multimorbidity, the presence of 2 or more chronic conditions,
frequently affects people with chronic obstructive pulmonary disease (COPD). Many
have high-cost, highly complex conditions that have a substantial impact on state
Medicaid programs. We quantified the cost of Medicaid-insured patients with COPD
co-diagnosed with other chronic disorders. METHODS: We used nationally
representative Medicaid claims data to analyze the impact of comorbidities (other
chronic conditions) on the disease burden, emergency department (ED) use,
hospitalizations, and total health care costs among 291,978 adult COPD patients.
We measured the prevalence of common conditions and their influence on COPD
related and non-COPD-related resource use by using the Elixhauser Comorbidity
Index. Elixhauser comorbidity counts were clustered from 0 to 7 or more. We
performed multivariable logistic regression to determine the odds of ED visits by
Elixhauser scores adjusting for age, sex, race/ethnicity, and residence. RESULTS:
Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as
the number of comorbidities increased. ED visits unrelated to COPD were more
common than visits for COPD, especially in patients self-identified as black or
African American (designated black). Hypertension, diabetes, affective disorders,
hyperlipidemia, and asthma were the most prevalent comorbid disorders. Substance
abuse, congestive heart failure, and asthma were commonly associated with ED
visits for COPD. Female sex was associated with COPD-related and non-COPD-related
ED visits. CONCLUSION: Comorbidities markedly increased health services use among
people with COPD insured with Medicaid, although ED visits in this study were
predominantly unrelated to COPD. Achieving excellence in clinical practice with
optimal clinical and economic outcomes requires a whole-person approach to the
patient and a multidisciplinary health care team.
PMID- 28409743
TI - PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a
positron emission tomography-computerised tomography-guided watch-and-wait policy
with planned neck dissection in the management of locally advanced (N2/N3) nodal
metastases in patients with squamous cell head and neck cancer.
AB - BACKGROUND: Planned neck dissection (ND) after radical chemoradiotherapy (CRT)
for locally advanced nodal metastases in patients with head and neck squamous
cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens
show histological evidence of tumour. Consequently, a significant proportion of
clinicians still practise planned ND. Fludeoxyglucose positron emission
tomography (PET)-computerised tomography (CT) scanning demonstrated high negative
predictive values for persistent nodal disease, providing a possible alternative
paradigm to ND. Evidence is sparse and drawn mainly from retrospective single
institution studies, illustrating the need for a prospective randomised
controlled trial. OBJECTIVES: To determine the efficacy and cost-effectiveness of
PET-CT-guided surveillance, compared with planned ND, in a multicentre,
prospective, randomised setting. DESIGN: A pragmatic randomised non-inferiority
trial comparing PET-CT-guided watch-and-wait policy with the current planned ND
policy in HNSCC patients with locally advanced nodal metastases and treated with
radical CRT. Patients were randomised in a 1 : 1 ratio. Primary outcomes were
overall survival (OS) and cost-effectiveness [incremental cost per incremental
quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the
trial period using individual patient data, and over a lifetime horizon using a
decision-analytic model. Secondary outcomes were recurrence in the neck,
complication rates and quality of life. The recruitment of 560 patients was
planned to detect non-inferior OS in the intervention arm with a 90% power and a
type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of
no higher than 1.50. An intention-to-treat analysis was performed by Cox's
proportional hazards model. SETTINGS: Thirty-seven head and neck cancer-treating
centres (43 NHS hospitals) throughout the UK. PARTICIPANTS: Patients with locally
advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult
HNSCC receiving CRT and fit for ND were recruited. INTERVENTION: Patients
randomised to planned ND before or after CRT (control), or CRT followed by
fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed
incomplete or equivocal response of nodal disease (intervention). Balanced by
centre, planned ND timing, CRT schedule, disease site and the tumour, node,
metastasis stage. RESULTS: In total, 564 patients were recruited (ND arm, n =
282; and surveillance arm, n = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty
four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases
were p16 positive. The median time to follow-up was 36 months. The HR for OS was
0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The
upper limit of the non-inferiority HR margin of 1.50, which was informed by
patient advisors to the project, lies at the 99.6 percentile of this estimate (p
= 0.004). There were no differences in this result by p16 status. There were 54
NDs performed in the surveillance arm, with 22 surgical complications, and 221
NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly
better in the surveillance arm. Compared with planned ND, PET-CT surveillance
produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28
QALYs) over the trial period and 0.21 QALYs (95% CI -0.41 to 0.85 QALYs) over the
modelled lifetime horizon. LIMITATIONS: Pragmatic randomised controlled trial
with a 36-month median follow-up. CONCLUSIONS: PET-CT-guided active surveillance
showed similar survival outcomes to ND but resulted in considerably fewer NDs,
fewer complications and lower costs, supporting its use in routine practice.
FUTURE WORK: PET-CT surveillance is cost-effective in the short term, and long
term cost-effectiveness could be addressed in future work. TRIAL REGISTRATION:
Current Controlled Trials ISRCTN13735240. FUNDING: This project was funded by the
National Institute for Health Research (NIHR) Health Technology Assessment
programme and will be published in full in Health Technology Assessment; Vol. 21,
No. 17. See the NIHR Journals Library website for further project information.
PMID- 28409744
TI - Long-Term Maintenance of Executive-Related Oculomotor Improvements in Older
Adults with Self-Reported Cognitive Complaints Following a 24-Week Multiple
Modality Exercise Program.
AB - Adults (>=55 years) with self-reported cognitive complaints (sCC) were randomized
to: multiple-modality exercise (M2), or multiple-modality plus mind-motor
exercise (M4), for 24-weeks. Participants (n = 58) were assessed on antisaccade
reaction time (RT) to examine executive-related oculomotor control and self
reported physical activity (PA) at pre-intervention (V0), post-intervention (V1),
and 52-weeks follow-up (V2). We previously reported significant improvements in
antisaccade RT of 23 ms at V1, in both groups. We now report maintenance of
antisaccade RT improvement from V1 to V2, t(57) = 0.8, p = 0.45, and improved PA
from V1 to V2, t(56) = -2.4, p = 0.02. Improvements in executive-related
oculomotor control attained at V1 were maintained at V2.
PMID- 28409745
TI - Mitochondria-Division Inhibitor 1 Protects Against Amyloid-beta induced
Mitochondrial Fragmentation and Synaptic Damage in Alzheimer's Disease.
AB - The purpose our study was to determine the protective effects of mitochondria
division inhibitor 1 (Mdivi1) in Alzheimer's disease (AD). Mdivi1 is hypothesized
to reduce excessive fragmentation of mitochondria and mitochondrial dysfunction
in AD neurons. Very little is known about whether Mdivi1 can confer protective
effects in AD. In the present study, we sought to determine the protective
effects of Mdivi1 against amyloid-beta (Abeta)- and mitochondrial fission
protein, dynamin-related protein 1 (Drp1)-induced excessive fragmentation of
mitochondria in AD progression. We also studied preventive (Mdivi1+Abeta42) and
intervention (Abeta42+Mdivi1) effects against Abeta42 in N2a cells. Using real
time RT-PCR and immunoblotting analysis, we measured mRNA and protein levels of
mitochondrial dynamics, mitochondrial biogenesis, and synaptic genes. We also
assessed mitochondrial function by measuring H2O2, lipid peroxidation, cytochrome
oxidase activity, and mitochondrial ATP. MTT assays were used to assess the cell
viability. Abeta42 was found to impair mitochondrial dynamics, lower
mitochondrial biogenesis, lower synaptic activity, and lower mitochondrial
function. On the contrary, Mdivi1 enhanced mitochondrial fusion activity, lowered
fission machinery, and increased biogenesis and synaptic proteins. Mitochondrial
function and cell viability were elevated in Mdivi1-treated cells. Interestingly,
Mdivi1 pre- and post-treated cells treated with Abeta showed reduced
mitochondrial dysfunction, and maintained cell viability, mitochondrial dynamics,
mitochondrial biogenesis, and synaptic activity. The protective effects of Mdivi1
were stronger in N2a+Abeta42 pre-treated with Mdivi1, than in N2a+Abeta42 cells
than Mdivi1 post-treated cells, indicating that Mdivi1 works better in prevention
than treatment in AD like neurons.
PMID- 28409746
TI - The Role of ADAM10 in Alzheimer's Disease.
AB - As a member of the A Disintegrin And Metalloproteinase (ADAM) family, ADAM10 has
been identified as the constitutive alpha-secretase in the process of amyloid
beta protein precursor (AbetaPP) cleavage and plays a critical role in reducing
the generation of the amyloid-beta (Abeta) peptides. Recent studies have
demonstrated its beneficial role in alleviating the pathologic impairment in
Alzheimer's disease (AD) both in vitro and in vivo. However, the role of ADAM10
in AD and the underlying molecular mechanisms are still not well established.
Increasing evidence indicates that ADAM10 not only reduces the generation of
Abeta but may also affect the pathology of AD through potential mechanisms
including reducing tau pathology, maintaining normal synaptic functions, and
promoting hippocampal neurogenesis and the homeostasis of neuronal networks.
Mechanistically, ADAM10 regulates these functions by interacting with
postsynaptic substrates in brain, especially synaptic cell receptors and adhesion
molecules. Furthermore, ADAM10 protein in platelets seems to be a promising
biomarker for AD diagnosis. This review will summarize the role of ADAM10 in AD
and highlight its functions besides its role as the alpha-secretase in AbetaPP
cleavage. Meanwhile, we will discuss the therapeutic potential of ADAM10 in
treating AD.
PMID- 28409747
TI - The Importance of Identifying Early Changes in Cardiac Structure and Function for
the Prevention of Cognitive Impairment and Dementia.
AB - Multiple cardiac pathologies have been shown to contribute to progressive
cognitive decline and dementia in elderly populations, including left ventricular
hypertrophy (LVH), a marker of prolonged exposure to hypertension. Although
associations between chronic hypertension and cognitive function are thought to
be mediated primarily by these end organ effects, there is increasing evidence
that early changes in cardiac structure and function, such as LVH, may
independently contribute to cognitive decline and impairment. In the current
issue of the Journal of Alzheimer's Disease, Mahinrad and colleagues report
important new findings on the association between LVH and cognitive function that
are incremental to cardiovascular risk and co-morbidity, including hypertension.
Emerging evidence that early changes in cardiac structure and function may
independently contribute to cognitive decline in elderly populations has resulted
in an increased interest in these preclinical substrates as potential treatment
targets for the prevention of cognitive decline and in their putative
contributions to the pathogenesis of dementia.
PMID- 28409748
TI - A Critical Assessment of Research on Neurotransmitters in Alzheimer's Disease.
AB - The purpose of this mini-forum, "Neurotransmitters and Alzheimer's Disease", is
to critically assess the current status of neurotransmitters in Alzheimer's
disease. Neurotransmitters are essential neurochemicals that maintain synaptic
and cognitive functions in mammals, including humans, by sending signals across
pre- to post-synaptic neurons. Authorities in the fields of synapses and
neurotransmitters of Alzheimer's disease summarize the current status of basic
biology of synapses and neurotransmitters, and also update the current status of
clinical trials of neurotransmitters in Alzheimer's disease. This article
discusses the prevalence, economic impact, and stages of Alzheimer's dementia in
humans.
PMID- 28409749
TI - The Role of Stress as a Risk Factor for Progressive Supranuclear Palsy.
AB - BACKGROUND: PSP, like Alzheimer's disease (AD), is a tauopathy. The
etiopathogenesis of PSP is not well known and the role of stress has not yet been
examined. Recent studies have shown that stress increases the risk for developing
AD. This study investigates the role of stress as a risk factor for PSP.
OBJECTIVE: B To examine the association between the development of progressive
supranuclear palsy (PSP) and self-reported life stressors. METHODS: 76 patients
diagnosed with PSP according to the NINDS-SPSP criteria and 68 age-matched
unrelated controls were administered a life stressor questionnaire. Stress was
quantified as total number of events, number of life changing events, and number
of events characterized by self-rated severity. Conditional odds ratio (OR) was
calculated for each measure, with participants in the highest quartile of each
measure being defined as high-exposure in relation to all other participants.
RESULTS: There were no significant differences between the reported number of
total events or life-changing events in cases and controls. However, we found
24.4% of cases (N = 11) and 9.1% of controls (N = 5) had a higher exposure to
high severity events, yielding an OR of 3.2 (p = 0.04). CONCLUSIONS: We found
that cases have over a three times greater odds of high exposure to high-severity
events than controls prior to the clinical development of PSP, while there were
no differences in overall number of reported events. Our findings suggest that
high exposure to highly stressful events may be associated with the development
of PSP.
PMID- 28409750
TI - Clinical Characteristics of Parkinson's Disease Developed from Essential Tremor.
AB - BACKGROUND: Recent genetic and epidemiological studies have shown that there is a
link between essential tremor and Parkinson's disease (PD). However, there is a
lack of data about the clinical features of PD developed from essential tremor.
OBJECTIVE: To explore and describe the clinical characteristics of Parkinson's
disease developed from essential tremor (ET-PD). METHODS: Twenty-five ET-PD
patients and 124 IPD controls were enrolled according to each criterion. Motor
and non-motor features and dopamine transporter uptake were compared between the
two groups. RESULTS: Rest and action tremors were more severe in ET-PD patients
than in IPD patients. In addition, tremor disorder of first-degree relatives
occurred more frequently in the ET-PD group than in the IPD group. A comparison
between cases with ET-PD and IPD was not significant for striatal dopamine
transporter uptake. Among the non-motor features, sleep disorder frequency,
especially rapid-eye-movement sleep behavioral disorder, were lower in patients
with ET-PD than in those with IPD, and smell identification test scores were
higher in patients with ET-PD than in those with IPD. The prevalence of other non
motor symptoms did not differ between the two groups. CONCLUSION: This is the
first comparison of motor and non-motor features between ET-PD and IPD. ET-PD and
IPD have different characteristic motor and non-motor features from the nosologic
perspective.
PMID- 28409751
TI - Early extubation failure in very low birth weight infants: Clinical outcomes and
predictive factors.
AB - OBJECTIVE: To identify the clinical outcomes and the potential predictive factors
of early extubation failure (EEF) in very low birth weight (VLBW) infants.
METHODS: A retrospective study of VLBW infants admitted to the neonatal intensive
care unit (NICU) over fifteen years. Neonates were intubated and mechanically
ventilated on the first day of life, and early extubated within the first 3 days.
EEF was defined as the need for re-intubation within 3 days of the first
extubation. A composite outcome of mortality or any major morbidity (grade 3-4
intraventricular hemorrhage or periventricular leukomalacia; stage 3-4
retinopathy of prematurity, moderate-severe bronchopulmonary dysplasia or stage 2
3 necrotizing enterocolitis) was assessed. RESULTS: In total, 394 infants were
extubated early. Of those, 347 (88%) had early extubation success (EES), whereas
47 (12%) had EEF. Incidence of the composite outcome was significantly higher in
the EEF group than the EES group, even after adjusting for confounding factors.
Logistic regression indicated that birth weight < 1000 g (p < 0.01),
administration of>=2 doses of surfactant (p < 0.01) and administration of>=2
inotropic agents (p < 0.01) were all significantly associated with EEF. The area
under the curve (AUC) for the combination of these three factors (AUC = 0.77)
indicated significantly higher predictive value (p < 0.01) for EEF in VLBW
infants, compared with individual factors (AUC = 0.59 for>=2 inotropic agents,
AUC = 0.64 for birth weight<=1000 g and AUC = 0.66 for>=2 doses of surfactant).
CONCLUSION: EEF is associated with poor clinical outcomes in VLBW infants. The
combination of birth weight and the requirement for surfactants and inotropic
agents can predict EEF.
PMID- 28409752
TI - Early appearance of tuberous sclerosis complex on cerebral ultrasound in
extremely preterm infant.
AB - Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder.
Diagnosis of early onset TSC in newborn infants is usually made by cardiac
ultrasound because of circulatory problems due to cardiac rhabdomyoma. Early
appearance of cortical tubers on cerebral ultrasound in newborn infants is very
rare. Mostly TSC is diagnosed on MRI and not by cerebral ultrasound. Subependymal
nodules are the usual presenting sign of TSC on cerebral ultrasound in neonates,
which are often misdiagnosed as subependymal hemorrhage, calcifications or
ischemic lesions after intrauterine germinal matrix hemorrhage. In this case
report, multiple cortical and subcortical tubers are demonstrated in an extremely
preterm infant, which were not observed on antenatal ultrasound. Together with
cardial rhabdomyoma and the identification of the TSC2 pathogenic mutation in DNA
from normal tissue the diagnosis of TSC has been confirmed. To our knowledge this
is the first case report of early appearance of disseminated cortical tubers on
cerebral ultrasound postnatal in an extremely preterm infant with TSC.
PMID- 28409753
TI - Short term cost of care for the surviving periviable neonate.
AB - OBJECTIVE: To determine the hospital cost and distribution of financial charges
for the initial hospitalization of the surviving periviable neonate. STUDY
DESIGN: In this retrospective case series, we analyzed medical records and
financial data for neonates 23-25 weeks' gestational age in a single tertiary
care NICU over 42 months. A detailed breakdown of hospital cost components and
charges was determined for all survivors during their initial hospitalization.
Statistical significance was determined using the Bonferroni-Sidak method.
RESULTS: Overall survival was 78% in infants born at 23-25 weeks' gestational
age. Survival increased and length of stay and hospital costs decreased with
increased gestational age (p < 0.05 for all). Hospital charges were distributed
as: NICU 56%, respiratory 11%, pharmacy 6%, laboratory 6%, radiology 6%, surgery
1%, neonatology 13% and miscellaneous 1%. CONCLUSION: Our study describes the
hospital cost and distribution of charges for the periviable neonate during the
initial hospitalization. These economic data may guide clinicians in quality
improvement and cost management.
PMID- 28409754
TI - The clinical utility of anthropometric measures to assess adiposity in a cohort
of prematurely born infants: Correlations with MRI fat quantification.
AB - OBJECTIVE: To correlate magnetic resonance imaging (MRI) of body fat in preterm
infants at the time of hospital discharge with same-day anthropometric measures,
and to assess the clinical utility of body mass index (BMI), waist circumference
(WC), and WC/length ratio as indicators of visceral fat. STUDY DESIGN: MRI
performed prior to NICU discharge in 25 infants born preterm at <32 weeks
gestation. Total body fat and visceral fat were quantified using a commercial
software program. The Pearson correlation coefficient (r, 95% C.I.) was used to
describe strength of association between MRI fat and anthropometric measures.
RESULTS: BMI and weight at discharge were strongly correlated with total body fat
(r = 0.95 and 0.89 respectively; p < 0.001). Total body fat as a % of body weight
was moderately correlated with weight (r = 0.53), WC (r = 0.52), and BMI (r =
0.47). Weight, BMI, and ponderal index all were found to correlate with total
visceral fat (r = 0.65, 0.64, 0.55 respectively) but WC did not (r = 0.28).
WC/length ratio was not correlated with any MRI fat measurements. CONCLUSIONS:
BMI and weight at discharge both correlate with MRI fat measurements. Our
findings do not support the usefulness of measuring WC or WC/length ratio in
preterm infants at term-equivalent age.
PMID- 28409755
TI - Serum cytokine concentrations, chorioamnionitis and the onset of bronchopulmonary
dysplasia in premature infants.
AB - OBJECTIVE: To investigate the relationships between serum cytokine concentrations
and chorioamnionitis (CAM) and CAM-related bronchopulmonary dysplasia (BPD) in
premature infants. METHODS: Serum was collected at 0 and 7 days after birth from
36 premature infants born at <32 weeks of gestation. We examined the
relationships between 30 cytokine concentrations and CAM, BPD, and other
perinatal factors. RESULTS: On day 0, GM-CSF, IL-15, IL-17, IL-2, IL-2R, VEGF,
and MIG concentrations were significantly higher in the CAM group (n = 17) than
in the non-CAM group (n = 19). These concentrations had decreased by day 7 and
were similar in both groups. The IL-12p70 concentration on day 0 was
significantly lower in the BPD group (n = 16) than in the non-BPD group (n = 15).
BPD incidence was similar between the CAM and non-CAM groups. CONCLUSIONS: These
data support the hypothesis that intrauterine inflammation is not a primary risk
factor for BPD. The immunological environment at birth or soon after, rather than
intrauterine fetal inflammation (e.g., CAM), is a primary risk factor for BPD
onset in preterm infants. Decreased inflammatory responses are particularly
relevant, as indicated by the relationship between BPD and low serum IL-12p70
concentrations on day 0.
PMID- 28409756
TI - Standardized slow enteral feeding protocol reduces necrotizing enterocolitis in
micropremies.
AB - BACKGROUND: Compared to early enteral feeds, delayed introduction and slow
enteral feeding advancement to reduce necrotizing enterocolitis (NEC) is not well
studied in micropremies (<750g birth weight). METHODS: Pre-post case control
study. Micropremies who followed a standardized slow enteral feeding (SSEF)
protocol (September 2009 to March 2015) were compared with a similar group of
historical controls (PreSSEF, January 2003 to July 2009). Enteral feeding
withheld for first 10-14 days and advanced at <10 ml/kg/day in the SSEF group.
RESULTS: Ninety-two infants in the SSEF group were compared with 129 PreSSEF
group. Birth weight and gestational age in SSEF and PreSSEF were similar. Breast
milk initiation rate was higher in SSEF (87.0 vs. 72.0%, p = 0.01) compared to
PreSSEF, but were similar at full enteral feeds. Compared with PreSSEF, feeding
initiation day, full enteral feeding day, parenteral nutrition days, and total
central line days were longer in SSEF. There was significant reduction in NEC
(1.1 vs. 16.2%, p < 0.01), surgical NEC (0.0 vs. 7.8%, p < 0.01) and NEC/death
(7.6 vs. 29.5%, p < 0.01), in SSEF compared to PreSSEF. SSEF, compared to
PreSSEF, had more cholestasis (41.8 vs 28.8%, p = 0.04), higher peak serum
alkaline phosphatase (638 vs. 534 IU/dL, p < 0.01), but similar rates of late
onset sepsis (39.1 vs 43.4%, p = 0.53). In infants who survived to discharge,
SSEF had higher discharge weight, lower extra-uterine growth restriction, and
similar length of stay, compared to PreSSEF. CONCLUSIONS: A SSEF protocol
significantly reduces the incidence of NEC and combined NEC/death in
micropremies.
PMID- 28409757
TI - Confirmation of posterior uterine rupture in the second trimester by magnetic
resonance imaging.
AB - Intrapartum uterine rupture is a life-threating and rare complication of
pregnancy which seldom occurs in the second trimester. Typically, the diagnosis
is made using ultrasound; however, magnetic resonance imaging can provide certain
advantages in the emergent setting. We present a unique case of a posterior
uterine rupture confirmed by magnetic resonance imaging involving the unscarred
posterior uterine wall in a 20-year-old gravid female with two previous cesarean
sections.
PMID- 28409758
TI - Improving neonatal intubation safety: A journey of a thousand miles.
AB - Neonatal intubation is one of the most common procedures performed by
neonatologists, however, the procedure is difficult and high risk. Neonates who
endure the procedure often experience adverse events, including bradycardia and
severe oxygen desaturations. Because of low first attempt success rates, neonates
are often subjected to multiple intubation attempts before the endotracheal tube
is successfully placed. These factors conspire to make intubation one of the most
dangerous procedures in neonatal medicine. In this commentary we review key
elements in the journey to improve neonatal intubation safety. We begin with a
review of intubation success rates and complications. Then, we discuss the
importance of intubation training. Next, we examine quality improvement efforts
and patient safety research to improve neonatal intubation safety. Finally, we
evaluate new tools which may improve success rates, and decrease complications
during neonatal intubation.
PMID- 28409759
TI - Influence of central hemodynamics on VV ECMO oxygen delivery in neonatal animal
model.
AB - BACKGROUND: Recirculation of oxygenated blood in venovenous extracorporeal
membrane oxygenation (VV ECMO) can decrease the oxygen delivery provided by the
ECMO support. This study investigated the influence of central hemodynamics and
catheter position on the amount of recirculation and oxygen delivery during VV
ECMO. METHODS: Recirculation was measured in seven newborn lambs (mean weight 4.7
kg) during VV ECMO using the ELSA Monitor (Transonic Systems, Inc., Ithaca, NY)
and using the central venous line (CVL) method. The ECMO pump was set at the
prescribed flow of 110-120 mL/kg/min for a targeted oxygen delivery rate of
6cc/kg/min without recirculation. Hemodynamic status before and during ECMO was
also measured by the COstatus Monitor (Transonic Systems, Inc.,Ithaca, NY).
RESULTS: Lambs with a higher cardiac index (>160 ml/min/kg), had a tendency to
have higher percent oxygen delivery (65-94%, at prescribed flow) while lambs with
lower cardiac index (<150 ml/min/kg), tended to have lower percent oxygen
delivery (39-62%, at prescribed flow). ELSA recirculation measurements had a
squared correlation coefficient R2 = 0.8 with the CVL method. CONCLUSIONS: The
ELSA monitor provides an easy to use, non-invasive method to measure
recirculation in VV ECMO. The data suggests that cardiac function may play an
important prognostic role in achieving effective VV ECMO support.
PMID- 28409760
TI - Delivery room continuous positive airway pressure and early pneumothorax in term
newborn infants.
AB - OBJECTIVE: To assess the association between delivery room (DR) continuous
positive airway pressure (CPAP) and pneumothorax (PT) in term newborns. METHODS:
Two studies performed in community hospitals used data extracted from
computerized records of term newborns. Infants receiving positive pressure
ventilation in the DR were excluded. Tabulated data included receipt of DR CPAP,
PT on the day of birth, and gestational age (GA). In a case-control study from
2001-2013, infants with PT were compared to controls without PT but with
respiratory distress or hypoxia persisting from birth for receipt of DR CPAP. In
a cohort study from 2014-2016, infants receiving and not receiving DR CPAP were
compared for the incidence of PT. RESULTS: In the case-control study, data were
obtained for 169 cases and 850 controls. Compared to controls, PT infants were
more likely to have received DR CPAP (16.8% vs. 40.2%, respectively, P < 0.001).
Logistic regression revealed DR CPAP (Adjusted Odds Ratio [AOR] = 3.30, 95%
confidence interval [CI] = 2.31, 4.72, P < 0.001) and GA (AOR = 1.21, 95% CI =
1.05, 1.39, P = 0.009) to be independent predictors of early PT.In the cohort
study, PT was observed in 0.1% of 9255 control infants not receiving DR CPAP and
4.8% of 228 infants receiving DR CPAP (P < 0.001). In logistic regression
analyses, DR CPAP significantly predicted PT (OR = 59.59, 95% CI = 23.34, 147.12,
P < 0.001) and remained a significant predictor of PT after controlling for
gestational age. CONCLUSION: Respiratory conditions treated with CPAP in delivery
rooms are associated with increased risk of PT. A cause-and-effect relationship
between CPAP and PT cannot be claimed in this study. Further research is needed
to better understand this relationship.
PMID- 28409761
TI - The question of whether or not to perform therapeutic hypothermia: A case of
neonatal spinal cord injury.
AB - Neonatal spinal cord injury is an extremely rare perinatal complication that
often occurs concurrently with hypoxic ischemic encephalopathy (HIE), further
complicating diagnosis of spinal cord injury. Although therapeutic hypothermia
for moderate to severe HIE is widely recommended in Japan, it is difficult to
determine whether it satisfies the neurological findings-related entry criteria
in some patients.We describe a female infant with neonatal spinal cord injury
after forceps delivery, who underwent therapeutic hypothermia upon diagnosis of
HIE. The Apgar scores were 5 at 1 min, 6 at 5 min, and not recorded at 10 min.
Blood gas analysis of her umbilical artery was not performed. Since respiratory
failure, hypotonia and the absence of primitive reflexes were found at 2 hours
after birth, she was initially diagnosed with moderate HIE and underwent a
therapeutic hypothermia. Magnetic resonance imaging after therapeutic hypothermia
revealed the spinal cord was narrowed from the lower medulla oblongata to the
upper cervical cord. Thus she was diagnosed with an upper spinal cord injury at
that time.Some patients with neonatal spinal cord injuries satisfy the criteria
for therapeutic hypothermia. When neonates with asphyxia present with prolonged
respiratory failure and hypotonia, spinal cord injury should be considered in the
differential diagnosis. Thus, an early MRI is vital for the diagnosis of spinal
cord injury.
PMID- 28409762
TI - Readmission for neonatal hyperbilirubinemia in an area with a high prevalence of
glucose-6-phosphate dehydrogenase deficiency: A hospital-based retrospective
study.
AB - BACKGROUND: Hyperbilirubinemia is one of the most common causes of neonatal
readmission to hospital. AIMS: To assess risk factors for hyperbilirubinemia
among neonates readmitted for this condition and the ratio of the mean
corpuscular hemoglobin concentration (MCHC) to the mean corpuscular volume (MCV).
METHODS: We retrospectively studied the clinical and laboratory findings,
management and possible risk factors for hyperbilirubinemia in 301 neonates born
at >=35 weeks gestation and readmitted to hospital owing to hyperbilirubinemia
over five years. RESULTS: No risk factors for hyperbilirubinemia were identified
in 64 (21.3%) neonates, and one or more risk factors were found in 237 neonates
(78.7%). The most prevalent risk factor (41.9%) was G6PD deficiency, which
occurred in 11 of the 15 neonates with a serum bilirubin level >=427 MUmol/l. A
double-volume exchange blood transfusion was performed in two neonate boys in
whom G6PD deficiency was the single risk factor for hyperbilirubinemia. One of
them developed kernicterus later. The MCHC/MCV ratio of neonates with idiopathic
hyperbilirubinemia, unexplained hemolysis, or other risk factors overlapped.
CONCLUSIONS: This study confirmed that in an area where G6PD deficiency is
prevalent, it is the most common and most severe risk factor for
hyperbilirubinemia. This finding supports routine neonatal screening for G6PD
deficiency in such areas. The usefulness of determining the MCHC/MCV ratio in the
management of hyperbilirubinemia is uncertain.
PMID- 28409763
TI - Work-related musculoskeletal disorders among Jordanian dental technicians:
Prevalence and associated factors.
AB - BACKGROUND: Dental technology is a profession that requires precise manual skills
and dexterous handling of small tools. There is an abundance research on work
related musculoskeletal disorders (WMSDs) affecting dentists, dental hygienists
and dental assistants, yet very few articles investigated WMSDs among dental
technicians. OBJECTIVES: This study aimed to determine the prevalence of WMSDs
among Jordanian dental technicians and their associated factors. METHODS: A cross
sectional design was conducted. A sample of Jordanian dental technicians (n = 81)
were asked to complete a validated structured self-administrated questionnaire to
measure WMSDs and its associated factors. RESULTS: A sample of 81 dental
technicians completed the survey (50.6% younger than 30 years, 61.7 were males).
Pain complains were significantly higher in female, younger technicians, and with
increased workload. All participants reported WMSDs in at least one body part in
the last 12 months. The most common pain areas reported were in the neck (70.4%)
and shoulders (71.6%). CONCLUSION: This study found a high prevalence of
musculoskeletal complaints in dental technicians. Future studies are indicated to
investigate the actual mechanisms causing WMSDs among dental technicians.
PMID- 28409764
TI - Using the narratives of Ontarians with a work-related traumatic brain injury to
inform injury prevention: A mixed methods approach.
AB - BACKGROUND: Work-related traumatic brain injury (wrTBI) is the most significant
occupational injury associated with death and disability. Few studies have
investigated injury text narratives to inform prevention strategies. OBJECTIVE:
To identify factors leading to wrTBI in male and female workers utilizing the
Person-Environment-Occupation (P-E-O) framework. METHODS: A retrospective chart
review of the medical records of 98 consecutive Ontario workers with a diagnosed
wrTBI was performed. Sociodemographic, occupational, injury-related, clinical,
and environmental data were collected from medical assessments and insurers'
files. A mixed methods approach was employed to analyse the data. RESULTS: Five
occupational hazard themes emerged from the injury narratives: unexplained person
factor, action by co-worker, external environment, safety measures, and equipment
malfunction. Male workers were more likely than female workers to experience a
wrTBI due to an equipment breakdown or malfunction. Statistically significant sex
differences were observed across P-E-O factors. CONCLUSION: Efforts directed at
identifying and remedying various injury patterns are necessary for the
development of brain injury primary prevention recommendations, to reduce the
prevalence of these vastly impactful incidents.
PMID- 28409765
TI - Effects of patient-handling and individual factors on the prevalence of low back
pain among nursing personnel.
AB - BACKGROUND: Patient-handling is one of the main tasks of nursing personnel; it
imposes compressive and shear forces on nurses' lower spine. The aim of this
study was to determine the prevalence of Low Back Pain (LBP), risk factors in the
incidence of such disorders, and patient handling risk assessment among nursing
personnel. METHODS: This study was carried out on 243 randomly selected nursing
personnel who played a role in handling the patients (58 wards). Patient Transfer
Assessment Instrument (PTAI) checklists alongside Standardized Nordic
Musculoskeletal Questionnaires (NMQ) were used for data collection. The
statistical analyses such as independent t-test and Chi-Square test were used.
RESULTS: Prevalence of LBP among nursing personal was 69.5% in the previous 12
months. Significant correlations were found among age, working hours per week,
work experience, BMI, gender and shift-work. Results of PTAI index assessment
revealed that more than 90% of subjects were in medium and severe risks of LBP.
PTAI index scores were significantly associated with LBP (P < 0.05). CONCLUSION:
PTAI index is regarded as an efficient tool for risk level classifications and
identification of effective factors on LBP incidence among nursing personnel
involved in patient transfer. In this regard and for the aim of ergonomic
intervention towards the reduction of LBP incidence among nurses, the
modification of improper factors which are identified in PTAI index such as the
use of advanced patient handling equipment, increase in work posture guidance and
work arrangements, can be mentioned.
PMID- 28409766
TI - Vocational situation and experiences from the work environment among individuals
with neuromuscular diseases.
AB - BACKGROUND: Neuromuscular diseases (NMD) can affect the ability to be employed
and to work, but there is limited knowledge of individuals' own perspectives of
factors that are important for their vocational situation. OBJECTIVE: To explore
the vocational situation among people with NMD that are employed, and to describe
their experiences of how their disability, personal and environmental factors
influence their ability to continue to work. METHODS: Nine participants with
different NMD were included. A mixed-methods design was used, and data were
collected by means of semi-structured and open-ended interviews, and ratings of
aspects supporting or interfering with their work performance and the ability to
continue to work. Data were analyzed with directed content analysis based on the
International Classification of Functioning, Disability and Health, and with
descriptive statistics. RESULTS: The participants' personal characteristics,
support from others at work and at home, and a flexible work organization were
perceived as important factors facilitating work continuation, whereas physically
demanding work assignments and factors in the physical environment were perceived
as barriers. CONCLUSIONS: Knowledge of how personal characteristics as well as
support from the work organization, managers and family members can facilitate
the ability to work is important for employers, staff within different parts of
the health care system, and the social security system. Future research should
focus on interventions that are best suited to enhance the vocational situation
for individuals with NMD.
PMID- 28409767
TI - Salutogenic resources in relation to teachers' work-life balance.
AB - BACKGROUND: Experiencing work-life balance is considered a health promoting
resource. To counter-balance the negative development of teachers' work
situation, salutogenic resources need to be examined among teachers. OBJECTIVE:
To examine resources related to teachers' experience of their work-life balance.
METHODS: Using a cross-sectional design, a questionnaire was distributed to 455
teachers in compulsory schools in a Swedish community. A total of 338 teachers
participated (74%). A multiple linear regression method was used for the
analysis. RESULTS: Four variables in the regression model significantly explained
work-life balance and were thereby possible resources: time experience at work;
satisfaction with everyday life; self-rated health; and recovery. The strongest
association with work-life balance was time experience at work. Except time
experience at work, all were individual-related. CONCLUSIONS: This study
highlights the importance of school management's support in reducing teachers'
time pressure. It also emphasizes the need to address teachers' individual
resources in relation to work-life balance. In order to support teachers' work
life balance, promote their well-being, and preventing teachers' attrition, we
suggest that the school management would benefit from creating a work environment
with strengthened resources.
PMID- 28409768
TI - Woman-to-woman rape and sexual assault, and its impact upon the occupation of
work: Victim/survivors' life roles of worker or student as disruptive and
preservative.
AB - BACKGROUND: Woman-to-woman rape and sexual assault globally remains largely
unknown and unaddressed. Expectedly, victim/survivors often cope alone, or with
limited support, in the traumatic aftermath of their sexual victimisation. Work
is one occupation that is impacted upon at this time. OBJECTIVE: The study
explored the perceived impacts of woman-to-woman rape and sexual assault, the
subsequent experience of disclosure, reaction, and support, and the consequences
for victim/survivors' subjective experience of occupation. METHODS: The study
combined a sociological auto/biographical approach with an occupational science
perspective. A web-based survey generated initial data, and was also used as a
sampling tool; subsequently, 10 respondents were interviewed face-to-face, in
various UK locations. An eleventh respondent shared her story through
correspondence. RESULTS: Four key themes emerged: 1) Identity; 2) Emotion; 3)
Survival; and 4) Occupation. The latter, occupation, incorporated study and work.
CONCLUSIONS: For these victim/survivors, work or education can be experienced as
either: disrupted (triggering) or as preservative (maintenance). Their life roles
as worker or student were impacted by feelings that they could have performed
better and achieved more. Occupational therapists and other relevant service
providers could work with sexually victimised people in order to participate more
satisfactorily and healthily in the occupation of work.
PMID- 28409770
TI - Acute myeloid leukemia targets for bispecific antibodies.
PMID- 28409769
TI - Investigation of the relationship between anthropometric measurements and maximal
handgrip strength in young adults.
AB - BACKGROUND: To identify physical measures that predict maximal handgrip strength
(MHGS) and provide evidence for identifying lack of sincerity of effort when
assessing upper extremity weakness. OBJECTIVE: This study investigated
anthropometric measurements associated with MHGS of healthy young adults.
METHODS: A convenience sample of 150 healthy adults ages 19 to 34 years old
completed the MHGS assessment, which was measured using a Jamar dynamometer
according to the protocol of the American Society of Hand Therapists, for both
dominant and non-dominant hands. Several anthropometric data were collected,
which included height, body weight, forearm length, forearm circumference, hand
length, and hand width. RESULTS: Multivariable linear regression analysis
indicated gender and hand width were uniquely and significantly associated with
participants' MHGS for dominant and non-dominant hand and accounted for more than
60% of the variance, with R2 = 0.60, P < 0.001 for the dominant hand model and R2
= 0.64, P < 0.001 for the non-dominant hand model. CONCLUSIONS: Among the forearm
and hand anthropometric measures, hand width is the best predictor of MHGS in
both the non-dominant and dominant hands for healthy young adults.
PMID- 28409771
TI - Early versus late traumatic cataract surgery and intraocular lens implantation.
AB - PurposeTo determine the proper time for traumatic cataract surgery after open
globe injuries.SettingFarabi Eye Hospital, Tehran University of Medical Sciences,
Tehran, Iran.DesignRandomized clinical trial.Patients and methodsIn a randomized
clinical trial, 30 eyes with traumatic cataract after open globe injury with IOL
implantation underwent early (in the first week after the trauma) and 30 eyes
underwent late cataract surgery (from the first to second month after the
trauma). We excluded patients who were under 12-year-old. All patients were
visited at 1 week, 4 weeks, 12 weeks, and 6 months after surgery. In each visit,
patients were examined regarding visual acuity, intraocular pressure (IOP),
anterior chamber inflammation, IOL position, and posterior synechiae. In
addition, posterior segment evaluation and fundoscopy were performed.
Intraoperative complication including posterior capsular rupture, anterior
vitrectomy, and zonulysis as well as the site of IOL implantation were documented
and post-operative complications including raised IOP, anterior chamber
inflammation, visual axis opacity, posterior synechiae, subluxation of IOL, and
IOL pigment deposition were listed.ResultsBest-corrected visual acuity 6 months
after surgery was not different between the two groups. Also in early cataract
surgery group, the rate of posterior capsular rupture was not significantly
higher than the late surgery group (P=0.069). On the other hand, zonulysis was
significantly higher in the late procedure group (P=0.039). Other complications
including anterior vitrectomy, raised IOP, anterior chamber inflammation, visual
axis opacity, posterior synechiae, subluxation of IOL, and IOL pigment deposition
were not different in the two groups.ConclusionsEarly and late traumatic cataract
surgery and IOL implantation after open globe injuries, have no significant
difference regarding the post-surgical BCVA and prominent intraoperative and post
operative complications.
PMID- 28409772
TI - Soil aggregates as massively concurrent evolutionary incubators.
PMID- 28409773
TI - The making of a mammalian peroxisome, version 2.0: mitochondria get into the mix.
AB - A recent report from the Laboratory of Heidi McBride (McGill University) presents
a role for mitochondria in the de novo biogenesis of peroxisomes in mammalian
cells. Peroxisomes are essential organelles responsible for a wide variety of
biochemical functions, from the generation of bile to plasmalogen synthesis,
reduction of peroxides, and the oxidation of very-long-chain fatty acids. Like
mitochondria, peroxisomes proliferate primarily through growth and division of
pre-existing peroxisomes. However, unlike mitochondria, peroxisomes do not fuse;
further, and perhaps most importantly, they can also be born de novo, a process
thought to occur through the generation of pre-peroxisomal vesicles that
originate from the endoplasmic reticulum. De novo peroxisome biogenesis has been
extensively studied in yeast, with a major focus on the role of the ER in this
process; however, in the mammalian system this field is much less explored. By
exploiting patient cells lacking mature peroxisomes, the McBride laboratory now
assigns a role to ER and mitochondria in de novo mammalian peroxisome biogenesis
by showing that the formation of immature pre-peroxisomes occurs through the
fusion of Pex3-/Pex14-containing mitochondria-derived vesicles with Pex16
containing ER-derived vesicles.
PMID- 28409775
TI - Optical pump-rejection filter based on silicon sub-wavelength engineered photonic
structures.
AB - The high index contrast of the silicon-on-insulator (SOI) platform allows the
realization of ultra-compact photonic circuits. However, this high contrast
hinders the implementation of narrow-band Bragg filters. These typically require
corrugation widths of a few nanometers or double-etch geometries, hampering
device fabrication. Here we report, for the first time, to the best of our
knowledge, on the realization of SOI Bragg filters based on sub-wavelength index
engineering in a differential corrugation width configuration. The proposed
double periodicity structure allows narrow-band rejection with a single etch step
and relaxed width constraints. Based on this concept, we experimentally
demonstrate a single-etch, 220 nm thick, Si Bragg filter featuring a corrugation
width of 150 nm, a rejection bandwidth of 1.1 nm, and an extinction ratio
exceeding 40 dB. This represents a 10-fold width increase, compared to
conventional single-periodicity, single-etch counterparts with similar
bandwidths.
PMID- 28409776
TI - Robust, low-noise, polarization-maintaining mode-locked Er-fiber laser with a
planar lightwave circuit (PLC) device as a multi-functional element.
AB - We demonstrate a new planar lightwave circuit (PLC)-based device, integrated with
a 980/1550 wavelength division multiplexer, an evanescent-field-interaction-based
saturable absorber, and an output tap coupler, which can be employed as a multi
functional element in mode-locked fiber lasers. Using this multi-functional PLC
device, we demonstrate a simple, robust, low-noise, and polarization-maintaining
mode-locked Er-fiber laser. The measured full-width at half-maximum bandwidth is
6 nm centered at 1555 nm, corresponding to 217 fs transform-limited pulse
duration. The measured RIN and timing jitter are 0.22% [10 Hz-10 MHz] and 6.6 fs
[10 kHz-1 MHz], respectively. Our results show that the non-gain section of mode
locked fiber lasers can be easily implemented as a single PLC chip that can be
manufactured by a wafer-scale fabrication process. The use of PLC processes in
mode-locked lasers has the potential for higher manufacturability of low-cost and
robust fiber and waveguide lasers.
PMID- 28409777
TI - Selective reflection from an Rb layer with a thickness below lambda/12 and
applications.
AB - We have studied the peculiarities of selective reflection from an Rb vapor cell
with a thickness L<70 nm, which is smaller than the length scale of evanescent
fields lambda/2pi and more than an order of magnitude smaller than the optical
wavelength. A 240 MHz redshift due to the atom-surface interaction is observed
for a cell thickness of L=40 nm. In addition, complete frequency-resolved
hyperfine Paschen-Back splitting of atomic transitions to four components for
Rb87 and six components for Rb87 is recorded in a strong magnetic field (B>2
kG).
PMID- 28409778
TI - Linewidth enhancement factor measurement based on FM-modulated optical injection:
application to rare-earth-doped active medium.
AB - A new method for measuring the linewidth enhancement factor of a laser is
proposed. It is based on frequency-modulated optical injection, combined with
dual-frequency laser operation. The linewidth enhancement factor alpha is deduced
from the experimental data using a theoretical analysis based on a standard rate
equation model. As the intracavity power is kept constant, the method frees the
process from the thermal effects that are usually present in AM/FM techniques.
Measurement of alpha=0.28+/-0.04 in a diode-pumped Nd:YAG laser demonstrates that
the method is well-suited for characterizing small values of alpha.
PMID- 28409774
TI - DR5 and caspase-8 are dispensable in ER stress-induced apoptosis.
AB - The endoplasmic reticulum (ER) stress response constitutes cellular reactions
triggered by a wide variety of stimuli that disturb folding of proteins, often
leading to apoptosis. ER stress-induced apoptotic cell death is thought to be an
important contributor to many human pathological conditions. The molecular
mechanism of this apoptosis process has been highly controversial with both the
receptor and the mitochondrial pathways being implicated. Using knockout mouse
models and RNAi-mediated gene silencing in cell lines, our group and others had
demonstrated the importance of the mitochondrial apoptotic pathway in ER stress
induced cell death, particularly the role of the pro-apoptotic BH3-only BCL-2
family members, BIM and PUMA. However, a recent report suggested a central role
for the death receptor, DR5, activated in a ligand-independent manner, and the
initiator caspase, caspase-8, in ER stress-induced cell death. This prompted us
to re-visit our previous observations and attempt to reproduce the newly
published findings. Here we report that the mitochondrial apoptotic pathway,
activated by BH3-only proteins, is essential for ER stress-induced cell death and
that, in contrast to the previous report, DR5 as well as caspase-8 are not
required for this process.
PMID- 28409779
TI - Four-wave mixing Bragg scattering in hydrogenated amorphous silicon waveguides.
AB - We demonstrate 15% on-chip conversion efficiency of four-wave mixing Bragg
scattering in a hydrogenated amorphous silicon waveguide with only 55 and 194 mW
peak pump powers in the waveguide. The lightwaves can be maintained in the
telecommunication band, and the operational bandwidth is measured to be larger
than 4 nm.
PMID- 28409780
TI - Compact interferometric module for full-field interferometric phase microscopy
with low spatial coherence illumination.
AB - We propose a compact and external off-axis interferometric module that can
achieve interference with low spatial coherence illumination over the entire
field of view. The interferometer is easy to align and stable and can be
connected to the output of an existing microscope illuminated with a low spatial
coherence light source, thus allowing quantitative phase imaging with a low
degree of spatial noise. We demonstrate the imaging and the interference
properties of the proposed interferometric module and use it for quantitative
phase imaging of reflective samples.
PMID- 28409781
TI - Interlinked add-drop filter with amplitude modulation routing a fiber-optic
microring to a lithium niobate microwaveguide.
AB - We propose and experimentally demonstrate a new electro-optically controllable
add-drop filter based on light coupling between a microfiber knot ring (MKR) and
a lithium niobate (LN) microwaveguide. In our design, the MKR works as a
resonator and routes the resonant light into the LN microwaveguide. The LN
microwaveguide, as an excellent intermediary between electronics and optics, is a
robust platform that not only enables stable support and manipulation of the MKR
but also provides amplitude tunability taking advantage of its electro-optic
property. Two add-drop filters with different diameters of the MKR, 1.12 mm, and
560 MUm respectively, are studied, and a maximum amplitude tunability of ~0.139
dB/V is obtained. The results show that this design can be a solution to
interconnect a microstructured optical fiber with a microstructured on-chip
device and provide an effective method to realize the active on-chip integration
of the conventional fiber system.
PMID- 28409782
TI - Controlling interface states in 1D photonic crystals by tuning bulk geometric
phases.
AB - There is no known simple rule that assures the existence of interface states in
photonic crystals (PCs). We show here that one can control the existence or
absence of interface states in 1D PCs through engineering the bulk geometrical
phase such that interface states can be guaranteed in some or all photonic
bandgaps. We verify experimentally the interface state design paradigm in 1D
multilayered PCs fabricated by electron beam vapor deposition. We obtain the
geometrical phases by measuring the reflection phases at the bandgaps of the PCs
and achieve good agreement with the theory. Our approach could provide a platform
for generating a PC interface state for various applications.
PMID- 28409783
TI - Ultra-broadband mid-wave-IR upconversion detection.
AB - In this Letter, we demonstrate efficient room temperature detection of ultra
broadband mid-wave-infrared (MWIR) light with an almost flat response over more
than 1200 nm, exploiting an efficient nonlinear upconversion technique. Black
body radiation from a hot soldering iron rod is used as the IR test source.
Placing a 20 mm long periodically poled lithium niobate crystal in a compact
intra-cavity setup (>20 W CW pump at 1064 nm), MWIR wavelengths ranging from 3.6
to 4.85 MUm are upconverted to near-infrared (NIR) wavelengths (820-870 nm). The
NIR light is detected using a standard low-noise silicon-based camera/grating
spectrometer. The proposed technique allows high conversion efficiency over a
wider bandwidth without any need for a shorter crystal length. Different
analytical predictions and numerical simulations are performed a priori to
support the experimental demonstrations.
PMID- 28409784
TI - Frequency stabilized diode laser with variable linewidth at a wavelength of 404.7
nm.
AB - We report on a frequency stabilized laser system with a variable linewidth at a
wavelength of 404.7 nm used as an incoherent repump on the 6P30<
>7S31 transition in mercury. By directly modulating the laser diode
current with Gaussian white noise, the laser linewidth can be broadened up to 68
MHz. A Doppler-free dichroic atomic vapor laser lock spectroscopy provides an
error signal suitable for frequency stabilization even for the broadened laser.
Without the need of an acousto-optic modulator for the linewidth tuning or lock
in technique for frequency stabilization, this laser system provides an
inexpensive approach for an incoherent and highly efficient repumper in atomic
experiments.
PMID- 28409785
TI - Partially coherent sources with circular coherence.
AB - A new class of partially coherent light sources is introduced. At the source
plane, they exhibit perfect coherence along any annulus that is concentric to the
source center. Between two points at different distances from the center,
coherence can be partial or even vanishing. Such sources can be synthesized by
using a generalized form of van Cittert-Zernike theorem where axial sources are
used. Beams radiated by this type of source are analyzed at the source plane and
upon free propagation for some simple cases.
PMID- 28409786
TI - Determining topological charge of an optical beam using a wedged optical flat.
AB - The topological charge of a beam carrying an optical vortex is an important
parameter that specifies the amount of orbital angular momentum carried by the
beam and the azimuthal order of the beam mode. We present an experimental method
to determine the sign and magnitude of the topological charge using a wedged
optical flat as a lateral shearing interferometer. When the curvature of the
wavefront is adjusted to be planar, the fringe pattern generated by the shearing
interferometer consists of two conjoined forks that unambiguously identify the
topological charge of the beam. We also investigated the changes in the pattern
when the wedged flat is rotated.
PMID- 28409787
TI - From parabolic-trough to metasurface-concentrator: assessing focusing in the wave
optics limit.
AB - Metasurfaces are promising tools toward novel designs for flat optics
applications. As such, their quality and tolerance to fabrication imperfections
need to be evaluated with specific tools. However, most such tools rely on the
geometrical optics approximation and are not straightforwardly applicable to
metasurfaces. In this Letter, we introduce and evaluate for metasurfaces
parameters such as intercept factor and slope error usually defined for solar
concentrators in the realm of ray-optics. After proposing definitions valid in
physical optics, we put forward an approach to calculate them. As examples, we
design three different concentrators based on three specific unit cells and
assess them numerically. The concept allows for comparison of the efficiency of
the metasurfaces and their sensitivities to fabrication imperfections and will be
critical for practical systems implementation.
PMID- 28409788
TI - Femtosecond semiconductor laser system with resonator-internal dispersion
adaptation.
AB - We present a femtosecond laser diode system that is capable of autonomously
adjusting itself to compensate for the external dispersion in an arbitrary
application. The laser system contains a spatial light modulator inside the
cavity which is controlled by an evolutionary algorithm in order to allow for
phase and amplitude shaping of the laser emission. The cavity-internal dispersion
control is shown to be much more efficient than an external control with a pulse
shaper.
PMID- 28409789
TI - Lasing in organic mixed-crystal thin films with cavities composed of naturally
formed cracks.
AB - This study investigates the possibility that a crack pair that is naturally
formed in the course of sample preparation functions as a laser cavity. Lasing
with longitudinal mode structures has been reported in mixed-crystal thin films
composed of fluorene and anthracene without artificial cavity structure. In the
present study, it was shown that lasing is observed only when an excitation spot
covers parallel pairs of cracks. The longitudinal mode intervals of the
stimulated emission spectra for several crack pairs were found to be proportional
to the inverse of the crack spacing. Furthermore, the interval for the
artificially fabricated metal cavity followed the same linear relation. These
results indicate that the crack pairs can function as laser cavities.
PMID- 28409790
TI - Mode-locked laser with pulse interleavers in a monolithic photonic integrated
circuit for millimeter wave and terahertz carrier generation.
AB - This Letter presents a photonics-based millimeter wave and terahertz frequency
synthesizer using a monolithic InP photonic integrated circuit composed of a mode
locked laser (MLL) and two pulse interleaver stages to multiply the repetition
rate frequency. The MLL is a multiple colliding pulse MLL producing an 80 GHz
repetition rate pulse train. Through two consecutive monolithic pulse interleaver
structures, each doubling the repetition rate, we demonstrate the achievement of
160 and 320 GHz. The fabrication was done on a multi-project wafer run of a
generic InP photonic technology platform.
PMID- 28409791
TI - Cavity-induced phase noise suppression in a Fabry-Perot modulator-based optical
frequency comb.
AB - We investigate for the first time, to the best of our knowledge, both
theoretically and experimentally, how the phase noise of the radio frequency (RF)
drive signal affects the phase noise of the individual tones of a Fabry-Perot (F
P) modulator-based optical frequency comb. We observe that the expected
deleterious effect of the RF drive signal phase noise on the comb output is
partially suppressed due to the filtering characteristics of the F-P cavity. We
found that the cavity-induced phase noise suppression is strongest for high-order
comb tones, e.g., reaching up to 40 dB for the 100th comb tone at high offset
frequencies. The phase noise suppression becomes even stronger for low RF-drive
powers, or when the seed laser does not resonate in the F-P cavity. For both
cases, we observe up to a 10 dB increase in phase noise suppression. We also
evaluate the timing jitter improvement obtained, thanks to the cavity-induced
phase noise reduction. The timing jitter (integrated from 2.5 MHz to 2.5 GHz)
decreased by a factor of 7 for the beat signal obtained between two comb tones
that are 100 tones apart (in comparison with the timing jitter obtained in a
cavity-less comb generator).
PMID- 28409792
TI - High-speed wavelength-swept source at 2.0 MUm and its application in imaging
through a scattering medium.
AB - We report a high-speed wavelength-swept source operating at 2.0 MUm through
advanced time-stretch technology. It sweeps over 30 nm at a speed of
3.3*109 nm/s and a repetition rate of ~19 MHz. To the best of our
knowledge, this is the first time that a megahertz-stable swept source has been
implemented at such a long wavelength. A wide bandwidth is enabled by a simple
mode-locked fiber laser that covers a wavelength range of ~60 nm. The all
optical wavelength sweeping is realized by a chirped fiber Bragg grating (CFBG),
which shows a superior temporal stability and power efficiency, compared with
commonly used dispersive fibers, particularly in the 2.0 MUm wavelength window.
To showcase its specialties, here we employ it to perform high-speed spectrally
encoded microscopy (i.e., time-stretch imaging) through a scattering medium at a
line-scan rate of up to ~19 MHz. Better image quality is achieved, compared with
a conventional imaging window at 1.0 MUm. It is believed that the potential
applications of this new high-speed swept source will benefit the transient
diagnosis that requires deep penetration through a scattering medium.
PMID- 28409793
TI - Diamond ring fiber for evanescent field exposure.
AB - Diamond Ring Fiber (DRF) is proposed to allow a high percentage of evanescent
field exposure while maintaining low confinement loss. It provides a long and
protected medium for light-matter interaction and large cavities to ease the
infiltration of sensing elements. DRFs with different waveguide parameters have
been analyzed theoretically and fabricated using a stack-and-draw fiber drawing
technique. Mode analysis has been performed experimentally on the fabricated
fibers, while the confinement loss and the percentage of evanescent field
exposure are examined by simulation. DRF allows evanescent field exposure as high
as 39.56% with negligible confinement loss at a wavelength of 1550 nm.
PMID- 28409794
TI - High-speed stimulated hyperspectral Raman imaging using rapid acousto-optic delay
lines.
AB - Stimulated Raman scattering (SRS) is a powerful, label-free imaging technique
that holds significant potential for medical imaging. To allow chemical
specificity and minimize spectral distortion in the imaging of live species, a
high-speed multiplex SRS imaging platform is needed. By combining a spectral
focusing excitation technique with a rapid acousto-optic delay line, we
demonstrate a hyperspectral SRS imaging platform capable of measuring a 3-dB
spectral window of ~200 cm-1 within 12.8 MUs with a scan rate of 30
KHz. We present hyperspectral images of a mixture of two different microsphere
polymers as well as live fungal cells mixed with human blood.
PMID- 28409795
TI - Low index contrast imaging fibers.
AB - We present high-resolution imaging fibers made from low-cost commercially
available fiber preforms manufactured for the telecommunications industry. Our
fabrication method involves multi-stacking arrays of different sized cores in
order to suppress core-to-core crosstalk whilst building up a large array of
cores. One of the fibers, based on a square array of cores, has comparable
imaging performance to commercial imaging fibers but without the need for
exceptionally high refractive index contrasts, and will enable the development of
economically viable single-use disposable imaging fibers.
PMID- 28409796
TI - Study of spinel LiTi2O4 superconductors via near-infrared
reflection experiments.
AB - We present an optical study on high-quality and single-phase
LiTi2O4 (LTO) superconductor thin films grown on
MgAl2O4 substrates by pulsed laser deposition. The near
infrared (NIR) reflectivity is measured for samples with (001) and (111) lattice
orientations. The temperature-induced metal-superconductor transition can be
observed, and the superconducting transition temperature can be measured for both
samples. We find that the NIR reflection experiment can reflect rightly the basic
features of LTO superconductor thin films. Furthermore, the results obtained from
this simple optical measurement suggest that the photo-induced electronic
localization effect can be present in LTO thin films in a metallic state. Such
information cannot be obtained directly from conventional transport and magneto
transport measurements. These interesting and important findings demonstrate that
the NIR reflection experiment is a powerful optical technique for contactless
characterizations and investigations of superconductor materials.
PMID- 28409797
TI - Ultrasensitive micro-scale parity-time-symmetric ring laser gyroscope.
AB - We propose a new scheme for ultrasensitive laser gyroscopes that utilizes the
physics of exceptional points. By exploiting the properties of such non-Hermitian
degeneracies, we show that the rotation-induced frequency splitting becomes
proportional to the square root of the gyration speed (Omega), thus enhancing the
sensitivity to low angular rotations by orders of magnitudes. In addition, at its
maximum sensitivity limit, the measurable spectral splitting is independent of
the radius of the rings involved. This Letter paves the way toward a new class of
ultrasensitive miniature ring laser gyroscopes on chip.
PMID- 28409798
TI - Controlled inhibition of spiking dynamics in VCSELs for neuromorphic photonics:
theory and experiments.
AB - We report experimentally and theoretically on the controllable inhibition of
spiking regimes in a 1300 nm wavelength vertical-cavity surface-emitting laser.
Reproducible suppression of spiking dynamics is demonstrated at fast operation
speeds (up to sub-ns rates) and with total control on the temporal duration of
the spiking inhibition windows. This Letter opens new paths toward a photonic
inhibitory neuronal model system for use in future neuromorphic photonic
information processing modules and which are able to operate at speeds up to 8
orders of magnitude faster than biological neurons.
PMID- 28409799
TI - Ultralong propagation of a surface plasmon polariton wave within an ultrawide
bandwidth via phase-sensitive optical parametric amplification.
AB - The propagation length enhancement of surface plasmon polariton (SPP) waves could
lead to practical applications. This Letter proposes the numerically verified
phase-sensitive nonlinear chi(2)-based optical parametric
amplification (OPA) for ultralong propagation of a SPP wave within an ultrawide
bandwidth. The strong nonlinear interaction between the SPP mode and the hybrid
guided mode, which limits the length enhancement, is mitigated in a silver-coated
linearly chirped periodically poled lithium niobate planar waveguide via slowly
phase-matched OPA. Obtained results indicate an ultralong propagation length for
a SPP mode of about 4 cm when a 135 MW/cm pump intensity is launched. The
acceptance bandwidth of the amplified SPP shows its dependency on the pump
intensity; for a pump intensity range between 70 and 135 MW/cm, the acceptance
bandwidth is still ultrawide, varying from 28 to 18 nm, respectively.
PMID- 28409800
TI - High-efficiency femtosecond Raman soliton generation with a tunable wavelength
beyond 2 MUm.
AB - We report an efficient Raman soliton laser system by optimizing the chirp of
input pulses. The highest efficiency of energy transferred to a Raman soliton is
up to 97%, and the tunable range is from 1.98 to 2.31 MUm. The pulse width of
these tunable Raman solitons remains below 200 fs. The efficiency and the
wavelength range are mainly limited by the background loss of the silica fiber.
PMID- 28409801
TI - Single-mode unidirectional microcavity laser.
AB - In this Letter, we report a suspended whispering gallery mode microdisk with a
hole pierced through its surface. The novel disk is made up of Rhodamine B-doped
resin, which is fabricated by femtosecond laser direct writing technology. The
pierced microcavity achieves highly directional emission of single-mode lasing
with a far field divergence angle of about 10 deg, and its high Q factor exceeds
2.6*103. The excellent properties are confirmed by numerical
simulation based on the finite-difference time-domain method. The effect of the
pierced hole on the microcavity performance is discussed in detail. The method is
easy to implement and has a guiding significance for improving the
characteristics of an existing microcavity by simple modification.
PMID- 28409802
TI - Coherent mode decomposition using mixed Wigner functions of Hermite-Gaussian
beams.
AB - A new method of coherent mode decomposition (CMD) is proposed that is based on a
Wigner-function representation of Hermite-Gaussian beams. In contrast to the well
known method using the cross spectral density (CSD), it directly determines the
mode functions and their weights without solving the eigenvalue problem. This
facilitates the CMD of partially coherent light whose Wigner functions (and thus
CSDs) are not separable, in which case the conventional CMD requires solving an
eigenvalue problem with a large matrix and thus is numerically formidable. An
example is shown regarding the CMD of synchrotron radiation, one of the most
important applications of the proposed method.
PMID- 28409803
TI - Design of ultracompact polarimeters based on dielectric metasurfaces.
AB - The state of polarization (SOP) is the key characteristic of light; its
evaluation is typically based on measurements of the Stokes parameters. However,
conventional approaches often have bulky and complex optical systems with long
acquisition times. In this Letter, an ultracompact polarimeter based on
dielectric metasurfaces is proposed. The pixel of the proposed metasuface has
four areas; each area acts not only as a polarization separator, but also a flat
focusing lens. It can acquire a certain polarization component of the incident
light and focus the component on the receiver. Therefore, the Stokes parameters
of the incident light can be immediately determined through the data from the
receiver, fully describing its SOP. The incident waves with different SOPs are
simulated to demonstrate that the reconstructed Stokes parameters are in good
agreement with the original ones.
PMID- 28409804
TI - Direct wide-angle measurement of a photonic band structure in a three-dimensional
photonic crystal using infrared Fourier imaging spectroscopy.
AB - We propose a method to directly visualize the photonic band-structure of
micrometer-sized photonic crystals using wide-angle spectroscopy. By extending
Fourier imaging spectroscopy sensitivity into the infrared range, we have
obtained accurate measurements of the band structures along the high-symmetry
directions (X-W-K-L-U) of polymeric three-dimensional, rod-connected diamond
photonic crystals. Our implementation also allows us to record single-wavelength
reflectance far-field patterns showing very good agreement with simulations of
the same designs. This technique is suitable for the characterization of photonic
structures working in the infrared and, in particular, to obtain band-structure
information of complete photonic band gap materials.
PMID- 28409805
TI - Continuous variable quantum key distribution with a real local oscillator using
simultaneous pilot signals.
AB - In this Letter, we propose a novel implementation of continuous variable quantum
key distribution that operates with a real local oscillator placed at the
receiver site. In addition, pulsing of the continuous wave laser sources is not
required, leading to an extraordinary practical and secure setup. It is suitable
for arbitrary schemes based on modulated coherent states and heterodyne
detection. The shown results include transmission experiments, as well as an
excess noise analysis applying a discrete 8-state phase modulation. Achievable
key rates under collective attacks are estimated. The results demonstrate the
high potential of the approach to achieve high secret key rates at relatively low
effort and cost.
PMID- 28409806
TI - All-polarization-maintaining, stretched-pulse Tm-doped fiber laser, mode-locked
by a graphene saturable absorber.
AB - In this Letter, we demonstrate an all-polarization-maintaining, stretched-pulse
Tm-doped fiber laser generating ~200 fs pulses centered at 1945 nm. As a
saturable absorber, a graphene/poly(methyl methacrylate) composite was used. To
the best of our knowledge, this is the first demonstration of stretched-pulse
operation of a graphene-based fiber laser at 2 MUm.
PMID- 28409807
TI - Bandwidth-adaptable silicon photonic differentiator employing a slow light
effect.
AB - A photonic differentiator (DIFF) plays a crucial role in photonic circuits.
Despite the fact that a DIFF having a terahertz bandwidth has been reported, the
practical bandwidth is limited to being a bandpass response. In this Letter, we
propose the concept of a bandwidth-adaptable DIFF, which exploits the slow light
effect in a photonic crystal waveguide (PhCW) to overcome the inherent bandwidth
limitation of current photonic DIFFs. We fabricated a PhCW Mach-Zehnder
interferometer (PhCW-MZI) on the silicon-on-isolator material platform to
validate our concept. Input Gaussian pulses with full width to half-maximums
(FWHMs) ranging from 2.7 to 81.4 ps are accurately differentiated using our PhCW
MZI. Our all-passive scheme circumvents the bandwidth bottlenecks of previously
reported photonic DIFFs and can greatly broaden the application area of photonic
DIFFs.
PMID- 28409808
TI - Aircraft-navigation-grade laser-driven FOG with Gaussian-noise phase modulation.
AB - A laser-driven fiber optic gyroscope (FOG) is demonstrated with an angular random
walk noise of 5.5*10-4 deg/?h, a drift of 6.8*10-3 deg/h,
and an inferred scale-factor stability of 0.15 ppm, making it, to the best of our
knowledge, the first laser-driven FOG to satisfy the performance requirements for
inertial navigation of commercial aircraft. This is achieved using Gaussian white
noise phase modulation to broaden the linewidth of the source laser and to
strongly suppress the narrow-linewidth optical carrier. The performance of this
laser-driven FOG is shown to have better noise and only slightly higher drift
than the same FOG driven by a conventional superfluorescent fiber source. This
result is validated for two lasers with widely different intrinsic coherence.
PMID- 28409809
TI - Plasmon-enhanced waveguide for dispersion compensation in mid-infrared quantum
cascade laser frequency combs.
AB - We demonstrate dispersion compensation in mid-infrared quantum cascade laser
frequency combs (FCs) emitting at 7.8 MUm using the coupling of a dielectric
waveguide to a plasmonic resonance in the top cladding layer of the latter.
Devices with group velocity dispersion lower than 110 fs2/mm were
fabricated, and narrow beatnotes with FWHM linewidths below 1 kHz were measured
on the entire operation range. At -20 degrees C, the optical output power reaches
275 mW, and the optical spectrum spans 60 cm-1. The multi-heterodyne
beating spectrum of two devices was measured and spans 46 cm-1,
demonstrating the potential of dispersion-engineered waveguides for the
fabrication of highly stable and reliable quantum cascade laser FCs with high
output power across the mid-infrared.
PMID- 28409810
TI - Characterization of a Ge1-x-ySiySnx/Ge1
xSnx multiple quantum well structure grown by sputtering
epitaxy.
AB - A high-quality
Ge0.88Si0.08Sn0.04/Ge0.94Sn0.06<
sub> multiple quantum well (MQW) structure was grown on a Ge (001) substrate by
sputtering epitaxy. The MQW structure was characterized by high-resolution x-ray
diffraction and transmission electron microscopy. Surface-illuminated
Ge0.88Si0.08Sn0.04/Ge0.94Sn0.06<
sub> MQW pin photodetectors were fabricated with cutoff wavelengths of up to 2140
nm. The analysis of transitions from spectral response was fitted well with the
theoretical calculations. Results suggest that sputtering epitaxy is a promising
method for preparing high-quality low-dimensional Sn-based group IV materials and
that Ge1-x-ySiySnx/Ge1
xSnx MQWs have potential applications in the development of
efficient Si-based photonic devices.
PMID- 28409811
TI - Rotationally symmetric formulation of the wave propagation method-application to
the straylight analysis of diffractive lenses.
AB - We introduce a modified formulation of the wave propagation method for the
efficient simulation of rotationally symmetric micro-optical components. The
reformulated algorithm provides an increased computational performance of
approximately two orders of magnitude and strongly reduced memory requirements,
in comparison to the original formulation. This enables the efficient wave
optical simulation of extended micro-optical structures beyond the common thin
element approximation. As a prototypical example, we assess the modified
algorithm for the evaluation of straylight induced by diffractive lenses. We find
an excellent accuracy, while comparing to rigorous simulations, which justifies
the ability to overcome the limitations of the thin-element approximation.
PMID- 28409812
TI - Laser-induced birefringence measurements by quantitative polarized-phase
microscopy.
AB - A technique that provides quantitative and spatially resolved retardance
measurement is studied for application to laser-induced modification in
transparent materials. The method is based on the measurement of optical path
differences between two wavefronts carrying different polarizations, measured by
a wavefront sensor placed in the image plane of a microscope. We have applied the
technique to the investigation of stress distribution induced by CO2
laser processing of fused silica samples. By comparing experiments to the results
of thermomechanical simulations we demonstrate quantitative agreement between
measurements and simulations of optical retardance. The technique provides an
efficient and simple way to measure retardance of less than 1 nm with a
diffraction-limited spatial resolution in transparent samples, and coupled to
thermomechanical simulations it gives access to birefringence distribution in the
sample.
PMID- 28409813
TI - Double-layer interlaced nested multi-ring array metallic mesh for high
performance transparent electromagnetic interference shielding.
AB - We report a nested multi-ring array metallic mesh (NMA-MM) that shows a highly
uniform diffraction pattern theoretically and experimentally. Then a high
performance transparent electromagnetic interference (EMI) shielding structure is
constituted by the double-layer interlaced NMA-MMs separated by transparent
quartz-glass substrate. Experimental results show that double-layer interlaced
NMA-MM structure exhibits a shielding effectiveness (SE) of over 27 dB in the Ku
band, with a maximal SE of 37 dB at 12 GHz, normalized optical transmittance of
90%, and minimal image quality degradation due to the interlaced arrangement. It
thus shows great potential for practical applications in transparent EMI
shielding devices.
PMID- 28409814
TI - Thin-disk laser operation of Ti:sapphire.
AB - We report on the first demonstration, to the best of our knowledge, of a
Ti:sapphire thin-disk laser oscillator, and discuss the thermal behavior and the
thermally induced lens for different sizes of the pump spot. In multimode cw
operation a maximum output power of 7 W was achieved with an optical efficiency
of 11%. The emission spectrum exhibits a spectral width of about 10 nm FWHM
centered at a wavelength of 790 nm.
PMID- 28409815
TI - High frequency continuous birefringence-induced oscillations in spin-polarized
vertical-cavity surface-emitting lasers.
AB - Sustained, large amplitude and tunable birefringence-induced oscillations are
obtained in a spin-vertical cavity surface-emitting laser (spin-VCSEL).
Experimental evidence is provided using a spin-VCSEL operating at 1300 nm, under
continuous-wave optical pumping and at room temperature. Numerical and stability
analyses are performed to interpret the experiments and to identify the combined
effects of pump ellipticity, spin relaxation rate, and cavity birefringence.
Importantly, the frequency of the induced oscillations is determined by the
device's birefringence rate, which can be tuned to very large values. This opens
the path for ultrafast spin-lasers operating at record frequencies exceeding
those possible in traditional semiconductor lasers and with ample expected impact
in disparate disciplines (e.g., datacomms, spectroscopy).
PMID- 28409816
TI - Regenerated volume gratings in PMMA after femtosecond laser writing.
AB - Self-regeneration of volume gratings recorded inside polymethyl methacrylate
(PMMA) after 70-100 days is demonstrated. First, volume gratings were made inside
PMMA by femtosecond laser writing. The diffraction efficiency of the gratings
reached the maximum-was regenerated-following an initial slow decrease within the
first several days after the fabrication. Time-lapse measurements of the
diffraction efficiency in both top-plane (as laser written) and side-plane
illumination were used to monitor changes of the diffraction efficiency. The
final efficiency was reaching values well in excess of the as-fabricated
efficiencies, with a maximum diffraction efficiency of 90% for the side readout
illumination. The regenerated volume grating is a possible candidate to achieve
high diffraction efficiency in PMMA. The regeneration is consistent with the
alpha-relaxation of the polymer structure and oxidation of the dangling bonds.
PMID- 28409817
TI - Silicon 16-QAM optical modulator driven by four binary electrical signals.
AB - We demonstrate a silicon 16-quadrature amplitude modulation (16-QAM) optical
modulator. Unlike traditional 16-QAM optical modulator with two Mach-Zehnder
modulators (MZMs) driven by two four-level electrical signals, the device is
based on four MZMs driven by four binary electrical signals. With the simple
electrical driving configuration, the device generates a 16-QAM optical signal at
20 Gbaud with an error vector magnitude of 13.7%.
PMID- 28409818
TI - Image quality recovery in binary ghost imaging by adding random noise.
AB - When the sampling data of ghost imaging are recorded with less bits, i.e.,
experiencing quantization, a decline in image quality is observed. The fewer bits
that are used, the worse the image one gets. Dithering, which adds suitable
random noise to the raw data before quantization, is proved to be capable of
compensating image quality decline effectively, even for the extreme binary
sampling case. A brief explanation and parameter optimization of dithering are
given.
PMID- 28409819
TI - Spermicidal efficacy of VRP, a synthetic cationic antimicrobial peptide, inducing
apoptosis and membrane disruption.
AB - Presently available contraceptives are mostly hormonal or detergent in nature
with numerous side effects like irritation, lesion, inflammation in vagina,
alteration of body homeostasis, etc. Antimicrobial peptides with spermicidal
activity but without adverse effects may be suitable alternatives. In the present
study, spermicidal activity of a cationic antimicrobial peptide VRP on human
spermatozoa has been elucidated. Progressive forward motility of human
spermatozoa was instantly stopped after 100 MUM VRP treatment and at 350 MUM, all
kinds of sperm motility ceased within 20 s as assessed by the Sander-Cramer
assay. The spermicidal effect was confirmed by eosin-nigrosin assay and HOS test.
VRP treatment (100 MUM) in human spermatozoa induced both the intrinsic and
extrinsic pathways of apoptosis. TUNEL assay showed VRP treatment significantly
disrupted the DNA integrity and changed the mitochondrial membrane permeability
as evident from MPTP assay. AFM and SEM results depicted ultra structural changes
including disruption of the acrosomal cap and plasma membrane of the head and
midpiece region after treatment with 350 MUM VRP. MTT assay showed after
treatments with 100 and 350 MUM of VRP for 24 hr, a substantial amount of
Lactobacillus acidophilus (about 90% and 75%, respectively) remained viable.
Hence, VRP being a small synthetic peptide with antimicrobial and spermicidal
activity but tolerable to normal vaginal microflora, may be a suitable target for
elucidating its contraceptive potentiality.
PMID- 28409820
TI - Identification and control of novel growth inhibitors in fed-batch cultures of
Chinese hamster ovary cells.
AB - Chinese hamster ovary (CHO) cells in culture are known to consume large amounts
of nutrients and divert most of them toward byproducts, some of which, including
lactate and ammonia, are known to be toxic in nature. Glucose limitation
strategies can successfully control lactate accumulation in fed-batch cultures
yielding higher peak cell densities and titers. Interestingly, even in such
optimized cultures, cell growth slows and eventually stops, indicating the
emergence of other factors that negatively affect cell growth. In this study, we
employed omics techniques to identify and quantify nine compounds that are
intermediates or byproducts of amino acid metabolism, and accumulate in fed-batch
cultures. Treatment with these compounds either individually or in a combined
fashion resulted in partial or complete cell growth inhibition. Careful control
of selected amino acid concentrations between one-half and one millimolar during
the growth phase of fed-batch cultures reduced accumulation of the inhibitory
metabolites and allowed for higher peak cell densities and increased
productivity. Biotechnol. Bioeng. 2017;114: 1779-1790. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28409821
TI - Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis
in pancreatic beta cells for effective management of Type 1 diabetes mellitus.
AB - BACKGROUND AND PURPOSE: Approaches to prevent selective and progressive loss of
insulin-producing beta cells in Type 1 diabetes mellitus (T1DM) will help to
manage this prevalent and devastating disease. Curcumin (CUR), a natural anti
inflammatory substance, suppresses diabetes-associated inflammation and cell
death. However, very high doses need to be used because of poor oral
bioavailability, making it difficult to translate the anti-inflammatory actions
to clinical situations. EXPERIMENTAL APPROACH: We have prepared biodegradable
nanosystems encapsulating curcumin (nCUR), resulting in at least nine-fold
improvement in oral bioavailability. Here, we tested the ability of nCUR to
prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic
islets and beta cells, in rats. KEY RESULTS: Non-fasted rats pretreated with 10
or 50 mg.kg-1 nCUR 6 h prior to STZ challenge had up to 37% reduction in the
glucose levels, while plain CUR (50 mg.kg-1 ) results in 12% reduction. This
treatment with nCUR was accompanied by decreased islet or beta cell death, as
shown by TUNEL assay and H&E staining. Both CUR and nCUR significantly decreased
levels of inflammatory cytokines in pancreatic tissue homogenates that correlated
well with minimal histiocytic infiltration. Pre-treatment with nCUR, but not CUR,
decreased 8-oxo-2'-deoxyguanosine, a sensitive biomarker of ROS-induced DNA
damage, in pancreas. In normal rodents, daily dosing for 28 days, with nCUR (25
100 mg.kg-1 ) did not cause any deleterious health issues by the carrier.
CONCLUSIONS AND IMPLICATIONS: Together, these data indicate a potentially
translatable dose of nCUR that is safe and efficacious in improving beta cell
function, which could prevent T1DM.
PMID- 28409822
TI - Non-hazardous biocatalytic oxidation in Nylon-9 monomer synthesis on a 40 g scale
with efficient downstream processing.
AB - This paper describes the development of a biocatalytic process on the multi-dozen
gram scale for the synthesis of a precursor to Nylon-9, a specialty polyamide.
Such materials are growing in demand, but their corresponding monomers are often
difficult to synthesize, giving rise to biocatalytic approaches. Here, we
implemented cyclopentadecanone monooxygenase as an Escherichia coli whole-cell
biocatalyst in a defined medium, together with a substrate feeding-product
removal concept, and an optimized downstream processing (DSP). A previously
described hazardous peracid-mediated oxidation was thus replaced with a safe and
scalable protocol, using aerial oxygen as oxidant, and water as reaction solvent.
The engineered process converted 42 g (0.28 mol) starting material ketone to the
corresponding lactone with an isolated yield of 70% (33 g), after highly
efficient DSP with 95% recovery of the converted material, translating to a
volumetric yield of 8 g pure product per liter. Biotechnol. Bioeng. 2017;114:
1670-1678. (c) 2017 Wiley Periodicals, Inc.
PMID- 28409823
TI - A sphingosine-1-phosphate receptor type 1 agonist, ASP4058, suppresses
intracranial aneurysm through promoting endothelial integrity and blocking
macrophage transmigration.
AB - BACKGROUND AND PURPOSE: Intracranial aneurysm (IA), common in the general public,
causes lethal subarachnoid haemorrhage on rupture. It is, therefore, of utmost
importance to prevent the IA from rupturing. However, there is currently no
medical treatment. Recent studies suggest that IA is the result of chronic
inflammation in the arterial wall caused by endothelial dysfunction and
infiltrating macrophages. The sphingosine-1-phosphate receptor type 1 (S1P1
receptor) is present on the endothelium and promotes its barrier function. Here
we have tested the potential of an S1P1 agonist, ASP4058, to prevent IA in an
animal model. EXPERIMENTAL APPROACH: The effects of a selective S1P1 agonist,
ASP4058, on endothelial permeability and migration of macrophages across an
endothelial cell monolayer were tested in vitro using a Transwell system, and its
effects on the size of IAs were evaluated in a rat model of IA. KEY RESULTS: S1P1
receptor was expressed in endothelial cells of human IA lesions and control
arterial walls. ASP4058 significantly reduced FITC-dextran leakage through an
endothelial monolayer and suppressed the migration of macrophages across the
monolayer in vitro. Oral administration of ASP4058 reduced the vascular
permeability, macrophage infiltration and size of the IAs by acting as an S1P1
agonist in the rat model. This effect was mimicked by another two structurally
unrelated S1P1 agonists. CONCLUSION AND IMPLICATIONS: A selective S1P1 agonist is
a strong drug candidate for IA treatment as it promotes the endothelial cell
barrier and suppresses the trans-endothelial migration of macrophages in IA
lesions.
PMID- 28409824
TI - A comparative genomic hybridization approach to study gene copy number variations
among Chinese hamster cell lines.
AB - Chinese Hamster Ovary (CHO) cells are aneuploid in nature. The genome of
recombinant protein producing CHO cell lines continuously undergoes changes in
its structure and organization. We analyzed nine cell lines, including parental
cell lines, using a comparative genomic hybridization (CGH) array focused on gene
containing regions. The comparison of CGH with copy-number estimates from
sequencing data showed good correlation. Hierarchical clustering of the gene copy
number variation data from CGH data revealed the lineage relationships between
the cell lines. On analyzing the clones of a clonal population, some regions with
altered genomic copy number status were identified indicating genomic changes
during passaging. A CGH array is thus an effective tool in quantifying genomic
alterations in industrial cell lines and can provide insights into the changes in
the genomic structure during cell line derivation and long term culture.
Biotechnol. Bioeng. 2017;114: 1903-1908. (c) 2017 Wiley Periodicals, Inc.
PMID- 28409827
TI - Topiramate for essential tremor.
AB - BACKGROUND: Essential tremor (ET) is one of the most common movement disorders.
The management is primarily based on pharmacological agents and in clinical
practice propranolol and primidone are considered the first-line therapy.
However, these treatments can be ineffective in 25% to 55% of people and are
frequently associated with serious adverse events (AEs). For these reasons, it is
worthwhile evaluating other treatments for ET. Topiramate has been suggested as a
potentially useful agent for the treatment of ET but there is uncertainty about
its efficacy and safety. OBJECTIVES: To assess the efficacy and safety of
topiramate in the treatment of ET. SEARCH METHODS: We carried out a systematic
search without language restrictions to identify all relevant trials in the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966
to January 2017), Embase (January 1988 to January 2017), National Institute for
Health and Care Excellence (1999 to January 2017), ClinicalTrials.gov (1997 to
January 2017) and World Health Organization International Clinical Trials
Registry Platform (ICTRP; 2004 to January 2017). We searched BIOSIS Citation
Index (2000 to January 2017) for conference proceedings. We handsearched grey
literature and the reference lists of identified studies and reviews. SELECTION
CRITERIA: We included all randomised controlled trials (RCTs) of topiramate
versus placebo/open control or any other treatments. We included studies in which
the diagnosis of ET was made according to accepted and validated diagnostic
criteria. We excluded studies conducted in people presenting with secondary forms
of tremor or reporting only neurophysiological parameters to assess outcomes.
DATA COLLECTION AND ANALYSIS: Two review authors independently collected and
extracted data using a data collection form. We assessed the risk of bias and the
quality of evidence. We used a fixed-effect meta-analysis for data synthesis.
MAIN RESULTS: This review included three trials comparing topiramate to placebo
(309 participants). They were all at high overall risk of bias. The quality of
evidence ranged from very low to low. Compared to placebo, participants treated
with topiramate showed a significant improvement in functional disability and an
increased risk of withdrawal (risk ratio (RR) 1.78, 95% confidence interval (CI)
1.23 to 2.60). There were more AEs for topiramate-treated participants,
particularly paraesthesia, weight loss, appetite decrease and memory difficulty.
AUTHORS' CONCLUSIONS: This systematic review highlighted the presence of limited
data and very low to low quality evidence to support the apparent efficacy and
the occurrence of treatment-limiting AEs in people with ET treated with
topiramate. Further research to assess topiramate efficacy and safety on ET is
needed.
PMID- 28409826
TI - Glycogen phosphorylase inhibition improves beta cell function.
AB - BACKGROUND AND PURPOSE: Glycogen phosphorylase (GP) is the key enzyme for
glycogen degradation. GP inhibitors (GPi-s) are glucose lowering agents that
cause the accumulation of glucose in the liver as glycogen. Glycogen metabolism
has implications in beta cell function. Glycogen degradation can maintain
cellular glucose levels, which feeds into catabolism to maintain insulin
secretion, and elevated glycogen degradation levels contribute to glucotoxicity.
The purpose of this study was to assess whether influencing glycogen metabolism
in beta cells by GPi-s affects the function of these cells. EXPERIMENTAL
APPROACH: The effects of structurally different GPi-s were investigated on MIN6
insulinoma cells and in a mouse model of diabetes. KEY RESULTS: GPi treatment
increased glycogen content and, consequently, the surface area of glycogen in
MIN6 cells. Furthermore, GPi treatment induced insulin receptor beta (InsRbeta),
Akt and p70S6K phosphorylation, as well as pancreatic and duodenal homeobox
1(PDX1) and insulin expression. In line with these findings, GPi-s enhanced non
stimulated and glucose-stimulated insulin secretion in MIN6 cells. The InsRbeta
was shown to co-localize with glycogen particles as confirmed by in silico
screening, where components of InsR signalling were identified as glycogen-bound
proteins. GPi-s also activated the pathway of insulin secretion, indicated by
enhanced glycolysis, mitochondrial oxidation and calcium signalling. Finally, GPi
s increased the size of islets of Langerhans and improved glucose-induced insulin
release in mice. CONCLUSION AND IMPLICATIONS: These data suggest that GPi-s also
target beta cells and can be repurposed as agents to preserve beta cell function
or even ameliorate beta cell dysfunction in different forms of diabetes. LINKED
ARTICLES: This article is part of a themed section on Inventing New Therapies
Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
PMID- 28409825
TI - Targeting inflammation to reduce cardiovascular disease risk: a realistic
clinical prospect?
AB - : Data from basic science experiments is overwhelmingly supportive of the causal
role of immune-inflammatory response(s) at the core of atherosclerosis, and
therefore, the theoretical potential to manipulate the inflammatory response to
prevent cardiovascular events. However, extrapolation to humans requires care and
we still lack definitive evidence to show that interfering in immune-inflammatory
processes may safely lessen clinical atherosclerosis. In this review, we discuss
key therapeutic targets in the treatment of vascular inflammation, placing basic
research in a wider clinical perspective, as well as identifying outstanding
questions. LINKED ARTICLES: This article is part of a themed section on Targeting
Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in
this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and
http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
PMID- 28409829
TI - Altitude exposure and increased heart rate: the role of the parasympathetic
nervous system.
PMID- 28409828
TI - Leucine elicits myotube hypertrophy and enhances maximal contractile force in
tissue engineered skeletal muscle in vitro.
AB - The amino acid leucine is thought to be important for skeletal muscle growth by
virtue of its ability to acutely activate mTORC1 and enhance muscle protein
synthesis, yet little data exist regarding its impact on skeletal muscle size and
its ability to produce force. We utilized a tissue engineering approach in order
to test whether supplementing culture medium with leucine could enhance mTORC1
signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1
target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a
dose dependent manner, with 5 and 20 mM of leucine inducing similar effects,
which were greater than those seen with 1 mM. Maximal contractile force was also
elevated with leucine supplementation; however, although this did not appear to
be enhanced with increasing leucine doses, this effect was completely ablated by
co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force
production in the presence of leucine was mTOR sensitive. Finally, by using
electrical stimulation to induce chronic (24 hr) contraction of engineered
skeletal muscle constructs, we were able to show that the effects of leucine and
muscle contraction are additive, since the two stimuli had cumulative effects on
maximal contractile force production. These results extend our current knowledge
of the efficacy of leucine as an anabolic nutritional aid showing for the first
time that leucine supplementation may augment skeletal muscle functional
capacity, and furthermore validates the use of engineered skeletal muscle for
highly-controlled investigations into nutritional regulation of muscle
physiology.
PMID- 28409830
TI - Magnesium for treating sickle cell disease.
AB - BACKGROUND: Sickle cell disease is an autosomal recessive inherited
haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red
blood cell dehydration. Vaso-occlusive crises are common painful events
responsible for a variety of clinical complications; overall mortality is
increased and life expectancy decreased compared to the general population.
Experimental studies suggest that intravenous magnesium has proven to be well
tolerated in individuals hospitalised for the immediate relief of acute (sudden
onset) painful crisis and has the potential to decrease the length of hospital
stay. Some in vitro studies and open studies of long-term oral magnesium showed
promising effect on pain relief but failed to show its efficacy. The studies show
that oral magnesium therapy may prevent sickle red blood cell dehydration and
prevent recurrent painful episodes. There is a need to access evidence for the
impact of oral and intravenous magnesium effect on frequency of pain, length of
hospital stay and quality of life. OBJECTIVES: To evaluate the effects of short
term intravenous magnesium on the length of hospital stay and quality of life in
children and adults with sickle cell disease. To determine the effects of long
term oral magnesium therapy on the frequency of painful crises and the quality of
life in children and adults with sickle cell disease. SEARCH METHODS: We searched
the Cochrane Haemoglobinopathies Trials Register, compiled from electronic
database searches and handsearching of journals and conference abstract
books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders
Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search
of other resources (clinical trials registries): 29 March 2017. SELECTION
CRITERIA: We searched for published and unpublished randomized controlled studies
of oral or intravenous magnesium compared to placebo or no magnesium. DATA
COLLECTION AND ANALYSIS: Authors independently assessed the study quality and
extracted the data using standard Cochrane methodologies. MAIN RESULTS: We
included five randomized placebo-controlled studies with a total of 386
participants (aged three to 53 years). Two shorter parallel studies (n = 306)
compared intravenous magnesium sulphate to placebo (normal saline) for admission
to hospital due to a vaso-occlusive crisis, for which we were able to analyse
data. The quality of evidence was moderate for studies presenting this comparison
mainly due to limitations due to risk of bias and imprecision. Two of the three
longer-term studies comparing oral magnesium pidolate to placebo had a cross-over
design. The third was a parallel factorial study which compared hydroxyurea and
oral magnesium to each other and to placebo over a longer period of time; we only
present the comparison of oral magnesium to placebo from this study. The quality
of evidence was very low with uncertainty of the estimation.The eight-hourly dose
levels in the two studies of intravenous magnesium were different; one used 100
mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104)
reported the mean daily pain score while hospitalised (a non-significant
difference between groups, moderate quality evidence). The second study (n = 202)
reported a number of child- and parent-reported quality of life scores. None of
the scores showed any difference between treatment groups (low quality evidence).
Data from one study (n = 106) showed no difference in length of stay in hospital
between groups (low quality evidence). Both studies reported on adverse events,
but not defined by severity as we had planned. One study showed significantly
more participants receiving intravenous magnesium experienced warmth at infusion
site compared to placebo; there were no differences between groups for other
adverse events (low quality evidence).Three studies (n = 80) compared oral
magnesium pidolate to placebo. None of them reported data which we were able to
analyse. One study (n = 24) reported on the number of painful days and stated
there was no difference between two groups (low quality evidence). None of the
studies reported on quality of life or length of hospital stay. Two studies (n =
68) reported there were no differences in levels of magnesium in either plasma or
red blood cells (moderate quality evidence). Two studies (n = 56) reported
adverse events. One reported episodes of mild diarrhoea and headache, all of
which resolved without stopping treatment. The second study reported adverse
events as gastrointestinal disorders, headache or migraine, upper respiratory
infections and rash; which were all evenly distributed across treatment groups
(moderate quality evidence). AUTHORS' CONCLUSIONS: Moderate to low quality
evidence showed neither intravenous magnesium and oral magnesium therapy has an
effect on reducing painful crisis, length of hospital stay and changing quality
of life in treating sickle cell disease. Therefore, no definitive conclusions can
be made regarding its clinical benefit. Further randomized controlled studies,
perhaps multicentre, are necessary to establish whether intravenous and oral
magnesium therapies have any effect on improving the health of people with sickle
cell disease.
PMID- 28409831
TI - Postoperative complications affect long-term outcomes after cytoreductive surgery
and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal
carcinomatosis.
AB - BACKGROUND AND OBJECTIVES: Morbidity after cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy (CRS + HIPEC) for colorectal peritoneal
carcinomatosis (PC) may negatively affect survival. The objective was to
determine the impact of postoperative complications (CX) on survival in patients
undergoing CRS + HIPEC for colorectal PC. METHODS: All patients undergoing
laparotomy for planned CRS + HIPEC for colorectal PC at a single institution from
1999 to 2014 were included. Patients were divided into three groups: CRS + HIPEC
without CX (+HIPEC-CX); CRS + HIPEC with postoperative complication (+HIPEC +
CX); and aborted CRS and HIPEC due to unresectable disease (-HIPEC).
Postoperative morbidity were defined as Clavien II+ complications. Kaplan-Meier
survival analyses and multivariable Cox proportional hazard modeling were used to
describe the disease-free (DFS) and overall survival (OS). RESULTS: One hundred
and twenty-two patients were included in the analysis (50 +HIPEC - CX, 40 +HIPEC
+ CX, 32-HIPEC). Overall complication rate was 42%. OS at 1-, 3-, and 5-years in
patients undergoing successful CRS + HIPEC were 97%, 67%, and 45%. CX after
successful CRS + HIPEC was independently associated with worsened OS (HR1.58,
95%CI, 1.19-1.97) but not DFS (HR1.11, 95%CI, 0.56-2.20). PCI also independently
predicted worsened DFS (HR1.12, 95%CI, 1.06-1.18) and OS (HR1.08, 95%CI, 1.04
1.12). Patients with unresectable disease had significantly worse OS (HR6.50,
95%CI, 1.37-7.01). CONCLUSIONS: CX after CRS + HIPEC significantly affect OS.
Patient selection and perioperative care are of paramount importance in the
management of CRS + HIPEC for colorectal PC.
PMID- 28409832
TI - Influence of neoadjuvant chemotherapy on resection of primary colorectal liver
metastases: A propensity score analysis.
AB - BACKGROUND AND OBJECTIVES: There is ongoing debate about whether patients planned
for liver resection of colorectal liver metastases (CRLM) benefit from
neoadjuvant chemotherapy (NC). Therefore, we performed a retrospective survival
analysis of patients with and without NC prior to surgery. METHODS: Data
prospectively collected from 468 consecutive patients were analyzed in a
retrospective design. We performed a survival analysis and added propensity score
matching (PSM). Univariate and multivariate analysis was performed to determine
independent prognostic risk factors. RESULTS: NC was performed in 145/468
patients. NC did not have a significant influence on overall survival (OS) either
before or after PSM. Patients receiving NC showed increased complication rates,
especially concerning non-surgical complications after primary resection (P =
0.025) of CRLM. Multivariate analysis before and after PSM revealed that the
Memorial Sloan Kettering Cancer Center (MSKCC) score and CEA values are strong
predictors for OS in patients with CRLM. CONCLUSIONS: NC was not associated with
increased OS in patients suffering from CRLM. Additionally, potentially harmful
chemotherapy prior to surgery increases the risk of postoperative complications
in these patients.
PMID- 28409833
TI - Dietary salt blunts vasodilation by stimulating epithelial sodium channels in
endothelial cells from salt-sensitive Dahl rats.
AB - BACKGROUND AND PURPOSE: Our recent studies show that the reduced activity of
epithelial sodium channels (ENaC) in endothelial cells accounts for the
adaptation of vasculature to salt in Sprague-Dawley rats. The present study
examines a hypothesis that enhanced ENaC activity mediates the loss of
vasorelaxation in Dahl salt-sensitive (SS) rats. EXPERIMENTAL APPROACH: We used
the cell-attached patch-clamp technique to record ENaC activity in split-open
mesenteric arteries. Western blot and immunofluorescence staining were used to
evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was
measured with the tail-cuff method and the artery relaxation was measured with
the wire myograph assay. KEY RESULTS: High-salt (HS) diet significantly increased
plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats.
The endothelium-dependent artery relaxation was blunted by HS challenge in these
rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and
NO and therefore prevented the HS-induced loss of vasorelaxation. As, in SS rats,
endogenous aldosterone was already elevated by HS challenge, exogenous
aldosterone did not further elevate ENaC activity in the rats fed with HS.
Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS
on both ENaC activity and artery relaxation. CONCLUSIONS AND IMPLICATIONS: These
data suggest that HS diet blunts artery relaxation and causes hypertension via a
pathway associated with aldosterone-dependent activation of ENaC in endothelial
cells. This pathway provides one of the mechanisms by which HS causes
hypertension in Dahl SS rats. LINKED ARTICLES: This article is part of a themed
section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the
other articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
PMID- 28409834
TI - Fully automatic detection of lung nodules in CT images using a hybrid feature
set.
AB - PURPOSE: The aim of this study was to develop a novel technique for lung nodule
detection using an optimized feature set. This feature set has been achieved
after rigorous experimentation, which has helped in reducing the false positives
significantly. METHOD: The proposed method starts with preprocessing, removing
any present noise from input images, followed by lung segmentation using optimal
thresholding. Then the image is enhanced using multiscale dot enhancement
filtering prior to nodule detection and feature extraction. Finally,
classification of lung nodules is achieved using Support Vector Machine (SVM)
classifier. The feature set consists of intensity, shape (2D and 3D) and texture
features, which have been selected to optimize the sensitivity and reduce false
positives. In addition to SVM, some other supervised classifiers like K-Nearest
Neighbor (KNN), Decision Tree and Linear Discriminant Analysis (LDA) have also
been used for performance comparison. The extracted features have also been
compared class-wise to determine the most relevant features for lung nodule
detection. The proposed system has been evaluated using 850 scans from Lung Image
Database Consortium (LIDC) dataset and k-fold cross-validation scheme. RESULTS:
The overall sensitivity has been improved compared to the previous methods and
false positives per scan have been reduced significantly. The achieved
sensitivities at detection and classification stages are 94.20% and 98.15%,
respectively, with only 2.19 false positives per scan. CONCLUSIONS: It is very
difficult to achieve high performance metrics using only a single feature class
therefore hybrid approach in feature selection remains a better choice. Choosing
right set of features can improve the overall accuracy of the system by improving
the sensitivity and reducing false positives.
PMID- 28409835
TI - Long-term outcomes with aspiration thrombectomy for patients undergoing primary
percutaneous coronary intervention: A meta-analysis of randomized trials.
AB - Randomized clinical trials that examined long-term clinical outcomes of routine
aspiration thrombectomy prior to primary percutaneous coronary intervention (PCI)
in patients with acute ST-segment elevation myocardial infarction have yielded
different results. We hypothesized that the routine use of manual thrombus
aspiration prior to primary PCI lacks long-term clinical benefits. Electronic
databases were searched for randomized trials comparing routine aspiration
thrombectomy and conventional PCI. We included only trials that reported clinical
outcomes beyond 6 months. The primary outcome was all-cause mortality, and the
secondary outcomes included major adverse cardiovascular events, re-infarction,
cardiovascular mortality, and stent thrombosis (ST). A DerSimonian-Laird model
was used to construct the summary estimates risk ratio (RR). We retrieved 18
trials with 20 641 ST-segment elevation myocardial infarction patients, of whom
10 331 patients underwent routine aspiration thrombectomy prior to primary PCI.
At a mean follow-up of 12 months, there was no significant decrease in the risk
of all-cause mortality (RR: 0.93, 95% confidence interval [CI]: 0.82-1.05, P =
0.22), major adverse cardiac events (RR: 0.95, 95% CI: 0.87-1.03, P = 0.18), re
infarction (RR: 0.95, 95% CI: 0.80-1.13, P = 0.59), cardiovascular mortality (RR:
0.80, 95% CI: 0.47-1.36, P = 0.40), or ST (RR: 0.80, 95% CI: 0.63-1.01, P = 0.06)
with routine aspiration thrombectomy. Routine aspiration thrombectomy prior to
primary PCI was not associated with a reduction in long-term mortality or
clinical outcomes. Future randomized trials are warranted to further evaluate the
role of aspiration thrombectomy in select patients and coronary lesions.
PMID- 28409836
TI - Platelet-derived microparticles regulates thrombin generation via
phophatidylserine in abdominal sepsis.
AB - Sepsis is associated with dysfunctional coagulation. Recent data suggest that
platelets play a role in sepsis by promoting neutrophil accumulation. Herein, we
show that cecal ligation and puncture (CLP) triggered systemic inflammation,
which is characterized by formation of IL-6 and CXC chemokines as well as
neutrophil accumulation in the lung. Platelet depletion decreased neutrophil
accumulation, IL-6, and CXC chemokines formation in septic lungs. Depletion of
platelets increased peak thrombin formation and total thrombin generation (TG) in
plasma from septic animals. CLP elevated circulating levels of platelet-derived
microparticles (PMPs). In vitro generated PMPs were a potent inducer of TG.
Interestingly, in vitro wild-type recombinant annexin V abolished PMP-induced
thrombin formation whereas a mutant annexin V protein, which does not bind to
phosphatidylserine (PS), had no effect. Administration of wild-type, but not
mutant annexin V, significantly inhibited thrombin formation in septic animals.
Moreover, CLP-induced formation of thrombin-antithrombin complexes were reduced
in platelet-depleted mice and in animals pretreated with annexin V. PMP-induced
TG attenuated in FXII- and FVII-deficient plasma. These findings suggest that
sepsis-induced TG is dependent on platelets. Moreover, PMPs formed in sepsis are
a potent inducer of TG via PS exposure, and activation of both the intrinsic and
extrinsic pathway of coagulation. In conclusion, these observations suggest that
PMPs and PS play an important role in dysfunctional coagulation in abdominal
sepsis.
PMID- 28409837
TI - Clinical accuracy of preoperative breast MRI for breast cancer.
AB - BACKGROUND: It is unclear if breast magnetic resonance imaging (MRI) is more
accurate than mammography (MGM) and ultrasound (U/S) in aggregate for patients
with invasive cancer. METHODS: We compared concordance of combined tumor size and
tumor foci between MRI and MGM and U/S combined to pathological tumor size and
foci as the gold standard from 2009 to 2015. Tumor size was nonconcordant if it
differed from the pathologic size by >=33% and tumor foci was nonconcordant if >1
foci were seen. If one or both of the MGM or U/S was nonconcordant and the MRI
was concordant, MRI provided greater accuracy. RESULTS: Of 471 patients with MGM,
US, and MRI, MRI was more accurate for 32.9% of patients for tumor size and for
21.9% for tumor foci. Patients for whom MRI had greater accuracy were compared to
those who did not for clinical and tumor factors. The only significant factor was
calcifications on mammography. Tumor size, stage, molecular subtype, histology,
grade, patient BMI, age, mammographic density, and use of hormone replacement
therapy were not significantly different. CONCLUSIONS: Breast MRI provides
greater accuracy for a third of patients undergoing preoperative MGM and U/S.
Mammographic calcifications were associated with MRI clinical accuracy for
patients with invasive cancer.
PMID- 28409838
TI - Modulation and modeling of monoclonal antibody N-linked glycosylation in
mammalian cell perfusion reactors.
AB - Mammalian cell perfusion cultures are gaining renewed interest as an alternative
to traditional fed-batch processes for the production of therapeutic proteins,
such as monoclonal antibodies (mAb). The steady state operation at high viable
cell density allows the continuous delivery of antibody product with increased
space-time yield and reduced in-process variability of critical product quality
attributes (CQA). In particular, the production of a confined mAb N-linked
glycosylation pattern has the potential to increase therapeutic efficacy and
bioactivity. In this study, we show that accurate control of flow rates, media
composition and cell density of a Chinese hamster ovary (CHO) cell perfusion
bioreactor allowed the production of a constant glycosylation profile for over 20
days. Steady state was reached after an initial transition phase of 6 days
required for the stabilization of extra- and intracellular processes. The
possibility to modulate the glycosylation profile was further investigated in a
Design of Experiment (DoE), at different viable cell density and media supplement
concentrations. This strategy was implemented in a sequential screening approach,
where various steady states were achieved sequentially during one culture. It was
found that, whereas high ammonia levels reached at high viable cell densities
(VCD) values inhibited the processing to complex glycan structures, the
supplementation of either galactose, or manganese as well as their synergy
significantly increased the proportion of complex forms. The obtained
experimental data set was used to compare the reliability of a statistical
response surface model (RSM) to a mechanistic model of N-linked glycosylation.
The latter outperformed the response surface predictions with respect to its
capability and reliability in predicting the system behavior (i.e., glycosylation
pattern) outside the experimental space covered by the DoE design used for the
model parameter estimation. Therefore, we can conclude that the modulation of
glycosylation in a sequential steady state approach in combination with
mechanistic model represents an efficient and rational strategy to develop
continuous processes with desired N-linked glycosylation patterns. Biotechnol.
Bioeng. 2017;114: 1978-1990. (c) 2017 Wiley Periodicals, Inc.
PMID- 28409839
TI - The Journal of Clinical Pharmacology, Clinical Pharmacology in Drug Development,
and the Impact Factor.
PMID- 28409841
TI - Intracranial pressure in outer space: preparing for the mission to Mars.
PMID- 28409842
TI - Development of cognitive screening test for the severely hearing impaired:
Hearing-impaired MoCA.
AB - OBJECTIVES: To develop a version of the Montreal Cognitive Assessment (MoCA) to
be administered to the severely hearing impaired (HI-MoCA), and to assess its
performance in two groups of cognitively intact adults over the age of 60. STUDY
TYPE: Test development followed by prospective subject recruitment. METHODS: The
MoCA was converted into a timed PowerPoint (Microsoft Corp., Redmond, WA)
presentation, and verbal instructions were converted into visual instructions.
Two groups of subjects over the age of 60 were recruited. All subjects passed
screening questionnaires to eliminate those with undiagnosed mild cognitive
impairment. The first group had normal hearing (group 1). The second group was
severely hearing impaired (group 2). Group 1 received either the MoCA or HI-MoCA
test (T1). Six months later (T2), subjects were administered the test (MoCA or HI
MoCA) they had not received previously to determine equivalency. Group 2 received
the HI-MoCA at T1 and again at T2 to determine test-retest reliability. RESULTS:
One hundred and three subjects were recruited into group 1, with a score of 26.66
(HI-MoCA) versus 27.14 (MoCA). This was significant (P < 0.05), but scoring uses
whole numerals and the 0.48 difference was found not clinically significant using
post hoc sensitivity analyses. Forty-nine subjects were recruited into group 2.
They scored 26.18 and 26.49 (HI-MoCA at T1 and T2). No significance was noted (P
> 0.05), with a test-retest coefficient of 0.66. CONCLUSION: The HI-MoCA is easy
to administer and reliable for screening cognitive impairment in the severely
hearing impaired. No conversion factor is required in our prospectively tested
cohort of cognitively intact subjects. LEVEL OF EVIDENCE: 1b. Laryngoscope,
127:S4-S11, 2017.
PMID- 28409843
TI - Reproducibility of quantitative high-throughput BI-RADS features extracted from
ultrasound images of breast cancer.
AB - PURPOSE: Digital Breast Imaging Reporting and Data System (BI-RADS) features
extracted from ultrasound images are essential in computer-aided diagnosis,
prediction, and prognosis of breast cancer. This study focuses on the
reproducibility of quantitative high-throughput BI-RADS features in the presence
of variations due to different segmentation results, various ultrasound machine
models, and multiple ultrasound machine settings. METHODS: Dataset 1 consists of
399 patients with invasive breast cancer and is used as the training set to
measure the reproducibility of features, while dataset 2 consists of 138 other
patients and is a validation set used to evaluate the diagnosis performances of
the final reproducible features. Four hundred and sixty high-throughput BI-RADS
features are designed and quantized according to BI-RADS lexicon. Concordance
Correlation Coefficient (CCC) and Deviation (Dev) are used to assess the effect
of the segmentation methods and Between-class Distance (BD) is used to study the
influences of the machine models. In addition, the features jointly shared by two
methodologies are further investigated on their effects with multiple machine
settings. Subsequently, the absolute value of Pearson Correlation Coefficient
(Rabs ) is applied for redundancy elimination. Finally, the features that are
reproducible and not redundant are preserved as the stable feature set. A 10-fold
Support Vector Machine (SVM) classifier is employed to verify the diagnostic
ability. RESULTS: One hundred and fifty-three features were found to have high
reproducibility (CCC > 0.9 & Dev < 0.1) within the manual and automatic
segmentation. Three hundred and thirty-nine features were stable (BD < 0.2) at
different machine models. Two feature sets shared the same 102 features, in which
nine features were highly sensitive to the machine settings. Forty-six features
were finally preserved after redundancy elimination. For the validation in
dataset 2, the area under curve (AUC) of the 10-fold SVM classifier was 0.915.
CONCLUSIONS: Three factors, segmentation results, machine models, and machine
settings may affect the reproducibility of high-throughput BI-RADS features to
various degrees. Our 46 reproducible features were robust to these factors and
were capable of distinguishing benign and malignant breast tumors.
PMID- 28409844
TI - Balloon Eustachian tuboplasty under local anesthesia: Is it feasible?
AB - OBJECTIVE: To study whether balloon Eustachian tuboplasty (BET) is a feasible and
safe procedure under local anesthesia. STUDY DESIGN: Prospective multicenter case
control study. METHODS: Patients undergoing either BET (n = 13) or endoscopic
sinus surgery (ESS) (n = 12) under local anesthesia, with the possibility of
sedation and analgesia, were monitored during the procedure and recovery period
for possible adverse effects. After the procedure, the patients responded to a
questionnaire assessing their experience. RESULTS: No adverse effects were
detected in the BET group. Patients in the BET group reported similar Visual
Analog Scale scores for pain during the operation as the ESS group (5.0 +/- 0.7
vs. 3.2 +/- 0.7, mean +/- standard error of the mean). However, patients in the
BET group experienced more discomfort (4.2 +/- 0.6 vs. 2.5 +/- 0.3, respectively,
P = 0.049). Seventy-seven and 92% of the patients in the BET and ESS groups,
respectively, considered the anesthesia and pain relief to be sufficient.
Patients from both the BET and ESS groups were almost devoid of pain 1 to 2 hours
postoperatively (0.8 +/- 0.2 and 1.4 +/- 0.3, respectively). In total, 12 of 13
patients in the BET group, and all 12 patients in the ESS group, would choose
local anesthesia with sedation and analgesia if they needed to undergo the same
procedure again. CONCLUSION: BET is a safe and feasible procedure under monitored
anesthesia care, including local anesthesia along with sedation and analgesia.
There is need for further methodological improvement to reduce pain and
discomfort during the operation. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1021
1025, 2017.
PMID- 28409845
TI - Procedural success and intra-hospital outcome related to left atrial appendage
morphology in patients that receive an interventional left atrial appendage
closure.
AB - BACKGROUND: The interventional left atrial appendage (LAA) closure represents an
emerging alternative to oral anticoagulation for stroke prevention in certain
atrial fibrillation patients. Preliminary results have suggested high procedural
success rates and fewer peri-interventional complications; however, there
persists an insufficient understanding of the role of many underlying confounding
variables (e.g., anatomical characteristics). HYPOTHESIS: It was investigated
whether varying LAA morphologies influence procedural success as well as in
hospital outcome. METHODS: Sixty-seven patients ineligible for long-term oral
anticoagulation were included in this single-center, prospective, observational
registry spanning from the years 2014 to 2016. Interventions were performed with
the Watchman occluder (Boston Scientific, Natick, MA) or the Amplatzer Amulet
(St. Jude Medical, St. Paul, MN), at the operator's discretion. Results derived
from the data describing procedural success, fluoroscopy, and peri-interventional
safety events were classified according to the presenting LAA morphology
(cauliflower, cactus, windsock, and chicken wing). RESULTS: Rates of successful
implantation were high across all groups (>=98%; P = 0.326). Surrogate parameters
underlining procedural complexity like median total duration (P = 0.415), median
fluoroscopy time (P = 0.459), median dose area product (P = 0.698), and the
median amount of contrast agent (P = 0.076) demonstrated similar results across
all groups. Likewise, the periprocedural complication rate was not significantly
different and was mainly restricted to minor bleeding events. CONCLUSIONS:
Irrespective of the varying morphological presentation of the LAA, the procedural
success rates, interventional characteristics, and safety events did not
significantly differ among patients receiving an interventional LAA closure.
PMID- 28409846
TI - An in vitro synthetic biology platform for the industrial biomanufacturing of myo
inositol from starch.
AB - Myo-Inositol (vitamin B8) is widely used in the drug, cosmetic, and food & feed
industries. Here, we present an in vitro non-fermentative enzymatic pathway that
converts starch to inositol in one vessel. This in vitro pathway is comprised of
four enzymes that operate without ATP or NAD+ supplementation. All enzyme
BioBricks are carefully selected from hyperthermophilic microorganisms, that is,
alpha-glucan phosphorylase from Thermotoga maritima, phosphoglucomutase from
Thermococcus kodakarensis, inositol 1-phosphate synthase from Archaeoglobus
fulgidus, and inositol monophosphatase from T. maritima. They were expressed
efficiently in high-density fermentation of Escherichia coli BL21(DE3) and easily
purified by heat treatment. The four-enzyme pathway supplemented with two other
hyperthermophilic enzymes (i.e., 4-alpha-glucanotransferase from Thermococcus
litoralis and isoamylase from Sulfolobus tokodaii) converts branched or linear
starch to inositol, accomplishing a very high product yield of 98.9 +/- 1.8%
wt./wt. This in vitro (aeration-free) biomanufacturing has been successfully
operated on 20,000-L reactors. Less costly inositol would be widely added in
heath food, low-end soft drink, and animal feed, and may be converted to other
value-added biochemicals (e.g., glucarate). This biochemical is the first product
manufactured by the in vitro synthetic biology platform on an industrial scale.
Biotechnol. Bioeng. 2017;114: 1855-1864. (c) 2017 Wiley Periodicals, Inc.
PMID- 28409847
TI - Trends in immediate breast reconstruction and early complication rates among
older women: A big data analysis.
AB - BACKGROUND: Although approximately 57% of breast cancer (BC) diagnoses are in
older patients (>60 years), only 4.1-14% receives breast reconstruction (BR).
This has been attributed to physician concerns about operative complications.
This paper aims to: 1) analyze the 30-day complication rates in the older patient
population undergoing immediate breast reconstruction (IBR); and 2) analyze links
between complication type and category of reconstruction. METHODS: Using the ACS
NSQIP database (2005-2014), all women older than 60 years of age diagnosed with
BC and DCIS were identified. IBR and complication rates were plotted for all
ages. Patients were divided into those with and those without complications.
Patient demographics and co-morbidities were compared. Complications within each
type of reconstruction were analyzed. RESULTS: Of the 4450 BC and 1104 DCIS
patients, 22.3% (BC) and 20.9% (DCIS) had complications. IBR decreased
significantly with increased age (P < 0.00 in both cohorts), while complication
rates remained stable across all ages (P = 0.32 in BC, P = 0.69 in DCIS
patients). Patients were well matched in terms of demographics. CONCLUSIONS: The
rates of breast reconstruction decrease with increasing age. Despite increasing
age, associated complication rates in IBR patients remained stable.
PMID- 28409848
TI - Density functional theory study of mechanism of epoxy-carboxylic acid curing
reaction.
AB - A comprehensive picture on the mechanism of the epoxy-carboxylic acid curing
reactions is presented using the density functional theory B3LYP/6-31G(d,p) and
simplified physical molecular models to examine all possible reaction pathways.
Carboxylic acid can act as its own promoter by using the OH group of an
additional acid molecule to stabilize the transition states, and thus lower the
rate-limiting barriers by 45 kJ/mol. For comparison, in the uncatalyzed reaction,
an epoxy ring is opened by a phenol with an apparent barrier of about 107 kJ/mol.
In catalyzed reaction, catalysts facilitate the epoxy ring opening prior to
curing that lowers the apparent barriers by 35 kJ/mol. However, this can be
competed in highly basic catalysts such as amine-based catalysts, where catalysts
can enhance the nucleophilicity of the acid by forming hydrogen-bonded complex
with it. Our theoretical results predict the activation energy in the range of 71
to 94 kJ/mol, which agrees well with the reported experimental range for
catalyzed reactions. (c) 2017 Wiley Periodicals, Inc.
PMID- 28409849
TI - Comparing the performance of TD-DFT and SAC-CI methods in the description of
excited states potential energy surfaces: An excited state proton transfer
reaction as case study.
AB - The performances, in the description of excited state potential energy surfaces,
of several density functional approximations representative of the currently most
applied exchange correlation functionals' families have been tested with respect
to post Hartree-Fock references (here Symmetry Adapted Cluster-Configuration
Interaction results). An experimentally well-characterized intermolecular proton
transfer reaction has been considered as test case. The computed potential energy
profiles were analyzed both in the gas phase and in toluene solution, here
represented as a polarizable continuum model. The presence of intermolecular
(dark) and intramolecular (bright) charge transfer excited states, whose polarity
strongly differs along the reaction pathway, makes clear that only subtle
compensation between spurious electronic effects-related to the incorrect
asymptotic behavior of the functional-and solvent stabilization of polar states
leads to the overall correct description of this excited state reaction when
using global hybrids with low percentage of Hartree Fock exchange. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28409850
TI - Mental Health Care: Call to Action.
PMID- 28409852
TI - Tandem mass spectrometric analysis of novel peptide-modified gemini surfactants
used as gene delivery vectors.
AB - Diquaternary ammonium gemini surfactants have emerged as effective gene delivery
vectors. A novel series of 11 peptide-modified compounds was synthesized, showing
promising results in delivering genetic materials. The purpose of this work is to
elucidate the tandem mass spectrometric (MS/MS) dissociation behavior of these
novel molecules establishing a generalized MS/MS fingerprint. Exact mass
measurements were achieved using a hybrid quadrupole orthogonal time-of-flight
mass spectrometer, and a multi-stage MS/MS analysis was conducted using a triple
quadrupole-linear ion trap mass spectrometer. Both instruments were operated in
the positive ionization mode and are equipped with electrospray ionization.
Abundant triply charged [M+H]3+ species were observed in the single-stage
analysis of all the evaluated compounds with mass accuracies of less than 8 ppm
in mass error. MS/MS analysis showed that the evaluated gemini surfactants
exhibited peptide-related dissociation characteristics because of the presence of
amino acids within the compounds' spacer region. In particular, diagnostic
product ions were originated from the neutral loss of ammonia from the amino
acids' side chain resulting in the formation of pipecolic acid at the N-terminus
part of the gemini surfactants. In addition, a charge-directed amide bond
cleavage was initiated by the amino acids' side chain producing a protonated
alpha-amino-epsilon-caprolactam ion and its complimentary C-terminus ion that
contains quaternary amines. MS/MS and MS3 analysis revealed common fragmentation
behavior among all tested compounds, resulting in the production of a universal
MS/MS fragmentation pathway. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28409851
TI - Response to a combination of oxygen and a hypnotic as treatment for obstructive
sleep apnoea is predicted by a patient's therapeutic CPAP requirement.
AB - BACKGROUND AND OBJECTIVE: Upper airway collapsibility predicts the response to
several non-continuous positive airway pressure (CPAP) interventions for
obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be
easily performed in a clinical context; however, a patient's therapeutic CPAP
requirement may serve as a surrogate measure of collapsibility. The present work
aimed to compare the predictive use of CPAP level with detailed physiological
measures of collapsibility. METHODS: Therapeutic CPAP levels and gold-standard
pharyngeal collapsibility measures (passive pharyngeal critical closing pressure
(Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were
retrospectively analysed from a randomized controlled trial (n = 20) comparing
the combination of oxygen and eszopiclone (treatment) versus placebo/air control.
Responders (9/20) to treatment were defined as those who exhibited a 50%
reduction in apnoea/hypopnoea index (AHI) plus an AHI<15 events/h on-therapy.
RESULTS: Responders to treatment had a lower therapeutic CPAP requirement
compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P =
0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017,
higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest
predictive accuracy for differentiating responders from non-responders (area
under the curve (AUC) = 0.86 +/- 0.9, 95% CI: 0.68-1.00, P = 0.007). However,
both Pcrit (AUC = 0.83 +/- 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC
= 0.77 +/- 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference
in AUC for these three metrics was not statistically different. A therapeutic
CPAP level <=8 cmH2 O provided 78% sensitivity and 82% specificity (positive
predictive value = 78%, negative predictive value = 82%) for predicting a
response to these therapies. CONCLUSION: Therapeutic CPAP requirement, as a
surrogate measure of pharyngeal collapsibility, predicts the response to non
anatomical therapy (oxygen and eszopiclone) for OSA.
PMID- 28409854
TI - How to face the low intrinsic sensitivity of 2D heteronuclear NMR with fast
repetition techniques: go faster to go higher!
AB - Nuclear magnetic resonance (NMR) is one of the most widely used analytical
techniques in numerous domains where molecules are objects of investigation.
However, major limitations of multidimensional NMR experiments come from their
low sensitivity and from the long times needed for their acquisition. In order to
overcome such limitations, fast repetition NMR techniques allowed for the
reduction of 2D experimental time and for the conversion of the gained time into
a higher number of scans leading to a better sensitivity. Thus, fast repetition
2D heteronuclear NMR techniques have allowed new advances in NMR, especially to
access infomation on low abundant nuclei, to enhance the detection of low
concentrated compounds and to probe weak interactions like hydrogen bonds at
natural abundance. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28409853
TI - A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose
cytarabine and etoposide in children with relapsed or refractory acute leukemias
or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics
Investigators' Consortium study (POE 10-03).
AB - BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions
between leukemic blasts and the bone marrow stromal microenvironment and may
enhance chemosensitivity. A phase 1 trial of plerixafor in combination with
intensive chemotherapy in children and young adults with relapsed or refractory
acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and
myelodysplastic syndrome (MDS) was performed to determine a tolerable and
biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days
at four dose levels (6, 9, 12, and 15 mg/m2 /dose) followed 4 hr later by high
dose cytarabine (every 12 hr) and etoposide (daily). RESULTS: Nineteen patients
(13 with AML, 5 with ALL, 1 with MDS) were treated. The most common grade 3 or
greater nonhematologic toxicities attributable to plerixafor were febrile
neutropenia and hypokalemia. There were no dose-limiting toxicities (DLTs).
Plerixafor exposure increased with increasing dose levels and clearance was
similar on days 1 and 5. Eighteen patients were evaluable for response. Two
patients achieved complete remission (CR) and one patient achieved CR with
incomplete hematologic recovery (CRi): all three had AML. No responses were seen
in patients with ALL or MDS. Plerixafor mobilized leukemic blasts into the
peripheral blood in 14 of 16 evaluable patients (median 3.4-fold increase), and
the degree of mobilization correlated with surface CXCR4 expression. CONCLUSIONS:
Plerixafor, in combination with high-dose cytarabine and etoposide, was well
tolerated in children and young adults with relapsed/refractory acute leukemias
and MDS. While biologic responses were observed, clinical responses in this
heavily pretreated cohort were modest.
PMID- 28409855
TI - The mobility of mitochondria: Intercellular trafficking in health and disease.
AB - The view that genes are constrained within somatic cells is challenged by in
vitro evidence, and more recently by in vivo studies which demonstrate that
mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do
move between cells in tumour models and in mouse models of tissue damage. Using
mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown
that these cells grow tumours only after acquiring mtDNA from cells in the local
microenvironment resulting in respiration recovery, tumorigenesis and metastasis.
Mitochondrial transfer between cells has also been demonstrated following
ischaemia-induced injury in the heart and brain and in lung epithelium, and
following lung inflammation. In vitro investigations suggest that stem cells may
be mitochondrial donors. The ability of mitochondria to move between cells
appears to be an evolutionarily-conserved phenomenon, relevant to diseases with
compromised mitochondrial function including neurodegenerative, neuromuscular and
cardiovascular diseases as well as cancer and ageing.
PMID- 28409856
TI - Pleural malignant mesothelioma in dental laboratory technicians: A case series.
AB - Asbestos was used in dentistry as a binder in periodontal dressings and as lining
material for casting rings and crucible. However, until now, only one case of
malignant mesothelioma with occupational exposure to asbestos in dental practice
has been reported. We present 4 pleural mesotheliomas out of 5344 cases
identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental
laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one
woman had been helping her husband for 30 years in manufacturing dental
prostheses. The men described the use of asbestos as a lining material for
casting rings, while the woman was not able to confirm this use. We confirm the
association of malignant mesothelioma with dental technician work. Dental
technicians suffering from mesothelioma should be questioned about past
occupational asbestos exposure.
PMID- 28409857
TI - Asbestos, asbestosis, and cancer: The Helsinki criteria for diagnosis and
attribution. Critical need for revision of the 2014 update.
PMID- 28409858
TI - Cancer studies in world trade center responders: Some comments.
PMID- 28409859
TI - Response to Soskolne [2017].
PMID- 28409860
TI - Hydrogenation of Carbon Dioxide to Methanol Catalyzed by Iron, Cobalt, and
Manganese Cyclopentadienone Complexes: Mechanistic Insights and Computational
Design.
AB - Density functional theory study of the hydrogenation of carbon dioxide to
methanol catalyzed by iron, cobalt, and manganese cyclopentadienone complexes
reveals a self-promoted mechanism, which features a methanol- or water-molecule
assisted proton transfer for the cleavage of H2 . The total free energy barrier
of the formation of methanol from CO2 and H2 catalyzed by Knolker's iron
cyclopentadienone complex, [2,5-(SiMe3 )2 -3,4-(CH2 )4 (eta5 -C4 COH)]Fe(CO)2 H,
is 26.0 kcal mol-1 in the methanol solvent. We also evaluated the catalytic
activities of 8 other experimentally reported iron cyclopentadienone complexes
and 37 iron, cobalt, and manganese cyclopentadienone complexes proposed in this
study. In general, iron and manganese complexes have relatively higher catalytic
activities. Among all calculated complexes, [2,5-(SiMe3 )2 -3,4-CH3 CHSCH2 (eta5
C4 COH)]Fe(CO)2 H (1Fe-Casey-S-CH3 ) is the most active one with a total free
energy barrier of 25.1 kcal mol-1 in the methanol solvent. Such a low barrier
indicates that 1Fe-Casey-S-CH3 is a very promising low-cost and high efficiency
catalyst for the conversion of CO2 and H2 to methanol under mild conditions.
PMID- 28409861
TI - Neocolonialism and Health Care Access among Marshall Islanders in the United
States.
AB - In the Marshall Islands, a history of extensive nuclear weapons testing and
covert biomedical research, coupled with the U.S.'s ongoing military presence in
the country, has severely compromised the health of the local population. Despite
the U.S.'s culpability in producing ill health along with high rates of
emigration from the islands to the mainland United States, the large portion of
Marshallese who reside in the United States face substantial barriers to
accessing health care. Drawing from ongoing field research with a Marshallese
community in Arkansas, this article explores the multifaceted impediments that
U.S.-based Marshall Islanders face in receiving medical treatment. Calling on an
expansive and inclusive notion of neocolonialism, I argue that Marshallese
structural vulnerability with regard to health and health care treatment derives
from their status as neocolonial subjects and from their limited claims to health
related deservingness associated with this status. [Marshall Islanders, health
care access, neocolonialism, radiation exposure, immigrant health] Lomnak ko
rottino: Ilo Majel, juon bwebwenato kon kommalmel im nuclear baam ko im ekkatak
ko rottino kon wawein an baijin ko jelot armej, barainwot an to an ri tarinae ro
an Amedka pad ilo aelon kein, emoj an jelot ajmour an armej ro ilo aelon kein.
Mene alikkar bwe Amedka in ear jino naninmej kein im ej un eo armej rein rej
emmakut jan ane kein ane er nan ioon Amedka, elon iaan ri Majel rein rej jelmae
elon apan ko nan aer delone jikin ajmour ko. Jan ekkatak eo ej bok jikin kio,
jerbal in ej etali kabojrak rak kein rolon im armej in Majel ro ioon Amedka in
rej jelmae ilo aer jibadok lok jikin takto. Ilo an kar Amedka jibadok juon jea eo
eutiej imejan lal in, ij kwalok juon ao akweelel bwe apan ko an armej in Majel
ikijjeen ajmour im jikin takto ej itok jan aer kar ri komakoko ilo an kar Amedka
lelon lok etan ilo mejan lal im jan aer jab pukot jipan kein ej aer bwe kon
jokjok in.
PMID- 28409862
TI - Synthesis and Properties of Salicylaldehydes Fine-Tuned by Modular Assembly using
"Plug-and-Socket"-Type Extendibility.
AB - A salicylaldehyde derivative bearing four pyridine arms, 3,5-bis(N,N-bis(2
pyridylmethyl)aminomethyl)-2,4-dihydroxybenzaldehyde (Hbpsal) as a "socket", was
prepared and used to derive a series of zinc complexes with various extra anions
"plugged" into their vacant site. The crystal structure and 1 H NMR spectra were
noticeably influenced by the extra anions, allowing fine-tuning of the properties
by "plug-and-socket"-type modification. Similar to unsubstituted salicylaldehyde,
the zinc complexes reacted with primary amines to afford Schiff-base compounds.
Because of the potential chirality around the coordination sphere, reaction with
a chiral amine resulted in an equilibrium system between diastereomers, the
potential of which as chiral sources tunable by the extra anions is discussed.
Some of the complexes were further converted into zinc- or nickel-salphen (=N,N
bis(salicylidene)-1,2-phenylenediamine) complexes. The electrochemical properties
of the nickel complex were slightly modified by the extra anions, whereas the
photophysical properties of the zinc complex appeared unchanged.
PMID- 28409863
TI - The influence of SNP-based chromosomal microarray and NIPT on the diagnostic
yield in 10,000 fetuses with and without fetal ultrasound anomalies.
AB - Prenatal diagnostics has been impacted by technological changes in the past
decade, which have affected the diagnostic yield. The aim of this study was to
evaluate the impact of SNP array and noninvasive prenatal testing (NIPT) on the
diagnostic yield and the number of invasive tests in our center. The frequency of
pathogenic fetal unbalanced chromosome aberrations was studied in 10,005 cases
referred for prenatal testing in 2009-2015. Chromosomal SNP microarray analysis
replaced karyotyping in all invasively tested pregnancies and since 2014 a choice
between NIPT and diagnostic testing with microarray was offered to women with an
increased risk for common aneuploidy. The introduction of microarray led to an
additional yield of submicroscopic pathogenic chromosome aberrations: 3.6% in
fetuses with ultrasound anomalies and 1.9% in fetuses without ultrasound
anomalies. The introduction of NIPT led to a decrease of invasive tests and of
diagnostic yield. Moreover, a diagnostic delay in about 1:350 cases was observed.
Since 20%-33% of pathogenic fetal chromosome aberrations are different from the
common aneuploidies and triploidy, whole-genome analysis should be offered after
invasive sampling. Because NIPT (as a second screening) has led to a decreased
diagnostic yield, it should be accompanied by an appropriate pretest counseling.
PMID- 28409864
TI - Secular change in adult stature associated with modernization in Vanuatu.
AB - OBJECTIVE: To determine whether: (1) there is a secular increase in adult stature
in Vanuatu, and (2) whether adult stature is positively associated with
modernization in Vanuatu. METHODS: This study reports on stature measurements
collected on 650 adult (age > 17 years) men and women from four islands of
varying economic development in Vanuatu. Measurements were collected as part of
the Vanuatu Health Transitions Research Project in 2007 and 2011. RESULTS:
Stature increased significantly in adults born between the 1940s and 1960s in
Vanuatu, before leveling off in those born between the 1970s and 1990s. Adults
are significantly taller on Efate, the most modernized island in the study
sample, than on the less economically developed islands. CONCLUSIONS:
Modernization is likely associated with improvements in child growth in Vanuatu,
as assessed by gains in adult stature.
PMID- 28409865
TI - Retention of glycopeptides analyzed using hydrophilic interaction chromatography
is influenced by charge and carbon chain length of ion-pairing reagent for mobile
phase.
AB - Characterization of the glycans of glycoproteins is essential for the development
and production of biologics. Numerous methods are available for analyzing the
glycans of glycoproteins directly and labeled glycans. Nevertheless,
glycopeptides are difficult to resolve because of their exceptional complexity
and the microheterogeneity of glycans. These properties represent technical
challenges to efforts to insure the accurate characterization of
biopharmaceuticals to comply with regulatory requirements. Therefore, we
investigated the retention behavior of peptides and glycopeptides in hydrophilic
interaction chromatography-mode HPLC in the presence of ion-pairing reagents.
Anionic ion-pairing reagents decreased the retention times of glycopeptides and
improved resolution in the presence of higher concentrations or hydrophobicities
of ion-pairing reagent. Anionic ion-pairing reagents increased retention times of
larger glycans because of their increased hydrophilicity. In contrast, in the
presence of cationic ion-pairing reagents, the retention times of glycopeptides
with greater numbers of sialic acid residues decreased. It is appropriate to add
an anionic ion-pairing reagent to the mobile phase for good separation of
glycopeptides. The collision cross-sectional area values of glycopeptides
determined using electrospray ionization-ion mobility spectrometry-mass
spectrometry correlated with retention times. These findings support the
implementation of hydrophilic interaction chromatography-mode HPLC to improve the
characterization of glycosylated biopharmaceuticals.
PMID- 28409866
TI - P. falciparum RH5-Basigin interaction induces changes in the cytoskeleton of the
host RBC.
AB - The successful invasion of Plasmodium is an essential step in their life cycle.
The parasite reticulocyte-binding protein homologues (RHs) and erythrocyte
binding like proteins are two families involved in the invasion leading to
merozoite-red blood cell (RBC) junction formation. Ca2+ signaling has been shown
to play a critical role in the invasion. RHs have been linked to Ca2+ signaling,
which triggers the erythrocyte-binding like proteins release ahead of junction
formation, consistent with RHs performing an initial sensing function in
identifying suitable RBCs. RH5, the only essential RHs, is a highly promising
vaccine candidate. RH5-basigin interaction is essential for merozoite invasion
and also important in determining host tropism. Here, we show that RH5 has a
distinct function from the other RHs. We show that RH5-Basigin interaction on its
own triggers a Ca2+ signal in the RBC resulting in changes in RBC cytoskeletal
proteins phosphorylation and overall alterations in RBC cytoskeleton
architecture. Antibodies targeting RH5 that block the signal prevent invasion
before junction formation consistent with the Ca2+ signal in the RBC leading to
rearrangement of the cytoskeleton required for invasion. This work provides the
first time a functional context for the essential role of RH5 and will now open
up new avenues to target merozoite invasion.
PMID- 28409867
TI - Amino-Acid-Derived Naphthalenediimides as Versatile G-Quadruplex Binders.
AB - The design and synthesis of water soluble, amino-acid-functionalised
naphthalenediimides (NDIs) as potential ligands of native G-quadruplexes is
reported. The NDIs were tested on a panel of oncogene promoters, on the human
telomeric sequence h-telo, and on double-stranded DNA. Out of the ligands tested,
NDI 3 (Nepsilon -Boc-l-lysine NDI) exhibited a highly discriminating nature by
only stabilising the oncogene promoter c-kit2, which is up-regulated up to 80 %
in ovarian, gastrointestinal, and breast malignancies.
PMID- 28409868
TI - Validated UHPLC-MS/MS assay for quantitative determination of etoposide,
gemcitabine, vinorelbine and their metabolites in patients with lung cancer.
AB - A fully valid UHPLC-MS/MS method was developed for the determination of
etoposide, gemcitabine, vinorelbine and their metabolites (etoposide catechol,
2',2'-difluorodeoxyuridine and 4-O-deacetylvinorelbine) in human plasma. The
multiple reaction monitoring mode was performed with an electrospray ionization
interface operating in both the positive and negative ion modes per compound. The
method required only 100 MUL plasma with a one-step simple de-proteinization
procedure, and a short run time of 7.5 min per sample. A Waters ACQUITY UPLC HSS
T3 column (2.1 * 100 mm, 1.8 MUm) provided chromatographic separation of analytes
using a binary mobile phase gradient (A, 0.1% formic acid in acetonitrile, v/v;
B, 0.1% formic acid in water, v/v). Linear coefficients of correlation were
>0.995 for all analytes. The relative deviation of this method was <10% for intra
and inter-day assays and the accuracy ranged between 86.35% and 113.44%. The
mean extraction recovery and matrix effect of all the analytes were 62.07-105.46%
and 93.67-105.87%, respectively. This method was successfully applied to clinical
samples from patients with lung cancer.
PMID- 28409869
TI - Single and combined effects of microcystin- and saxitoxin-producing cyanobacteria
on the fitness and antioxidant defenses of cladocerans.
AB - Cyanobacteria produce different toxic compounds that affect animal life, among
them hepatotoxins and neurotoxins. Because cyanobacteria are able to produce a
variety of toxic compounds at the same time, organisms may be, generally,
subjected to their combined action. In the present study, we demonstrate the
single and combined effects on cladocerans of cyanobacteria that produce
microcystins (hepatotoxins) and saxitoxins (neurotoxins). Animals were exposed
(either singly or combined) to 2 strains of cyanobacteria isolated from the same
environment (Funil Reservoir, Rio de Janeiro, Brazil). The effects on clearance
rate, mobility, survivorship, fecundity, population increase rate (r), and the
antioxidant enzymes glutathione-S-transferase (GST) and catalase (CAT) were
measured. Cladoceran species showed a variety of responses to cyanobacterial
exposures, going from no effect to impairment of swimming movement, lower
survivorship, fecundity, and general fitness (r). Animals ingested cyanobacteria
in all treatments, although at lower rates than good food (green algae).
Antioxidant defense responses were in accordance with fitness responses,
suggesting that oxidative stress may be related to such effects. The present
study emphasizes the need for testing combined actions of different classes of
toxins, because this is often, and most likely, the scenario in a more eutrophic
world with global climatic changes. Environ Toxicol Chem 2017;36:2689-2697. (c)
2017 SETAC.
PMID- 28409870
TI - Comparative Efficacy and Safety of Anti-Platelet Agents in Cerebral Ischemic
Disease: A Network Meta-Analysis.
AB - We performed this network meta-analysis (NMA) to enhance the corresponding
evidence of the relative efficacy and safety of different anti-platelet agents in
cerebral ischemic disease. PubMed and EMBASE were searched systematically for
relevant studies. Outcomes were compared using odds ratios (ORs) and 95% credible
intervals (CrI). Each agent was ranked according to the value of surface under
the cumulative ranking curve (SUCRA). Publication bias was evaluated by funnel
plots while consistency between direct and indirect comparison was analyzed by
node splitting and heat plots. Besides, clustering technique was used to
categorize similar agents. A number of 44 eligible studies with 148578 patients
were included in this NMA. In terms of efficacy (including mortality, recurrent
stroke and vascular event), all six interventions were better than placebo.
clopidogrel (Clop) and aspirin (ASA)+Clop were the best two interventions from
SUCRA. However, the performance of ASA+Clop declined significantly when
considering safety (including myocardial infarction, all-cause withdrawal and
intracranial hemorrhage), especially worse in intracranial hemorrhage. In
conclusion, Clop was potentially the most preferable treatment for preventing
cerebral ischemic in terms of efficacy and safety. However, the addition of ASA
was associated with a potential increase in intracranial hemorrhage, therefore,
combination therapy of ASA and Clop should be introduced with caution despite it
may be more effective than the monotherapy of ASA. This article is protected by
copyright. All rights reserved.
PMID- 28409871
TI - A Molecular Docking and Dynamics Approach to Screen Potent Inhibitors Against
Fosfomycin Resistant Enzyme in Clinical Klebsiella pneumoniae.
AB - Klebsiella pneumoniae, BA6753 was cultured from a patient in the Clinical
Microbiology Laboratory of Christian Medical College. K. pneumoniae, BA6753 has a
multidrug resistance plasmid encoding novel FosA variant-7, fosfomycin resistance
enzyme. Minimal side effects and a wide range of bactericidal activity of
fosfomycin have resulted in its expanded clinical use that prompts the rise of
fosfomycin-resistant strains. At present, there are no effective inhibitors
available to conflict the FosA-medicated fosfomycin resistance. To develop
effective FosA inhibitors, it is crucial to understand the structural and dynamic
properties of resistance enzymes. Hence, the present study focuses on the
identification of potent inhibitors that can effectively bind to the fosfomycin
resistance enzyme, thus predispose the target to inactivate by the second
antibiotic. Initially, a series of active compounds were screened against the
resistant enzyme, and the binding affinities were confirmed using docking
simulation analysis. For efficient activity, the binding affinity of the
resistance enzyme ought to be high with the inhibitor than the fosfomycin drug.
Consequently, the enzyme-ligand complex which showed higher binding affinity than
the fosfomycin was employed for subsequent analysis. The stability of the top
scoring enzyme-ligand complex was further validated using molecular dynamics
simulation studies. On the whole, we presume that the compound 19583672
demonstrates a higher binding affinity for the resistance enzyme comparing to
other compounds and fosfomycin. We believe that further enhancement of the lead
compound can serve as a potential inhibitor against resistance enzyme in drug
discovery process. J. Cell. Biochem. 118: 4088-4094, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28409874
TI - Editorial.
PMID- 28409880
TI - Osajin Inhibits Solar UV-Induced Cyclooxygenase-2 Expression Through Direct
Inhibition of RSK2.
AB - Solar ultraviolet light (sUV) has been shown to promote the development of skin
disorders including inflammation, photoaging, and skin carcinogenesis. Osajin is
the major bioactive isoflavone present in the fruit of Maclura pomifera, commonly
referred to as the Osage orange. In this study, we observed that osajin inhibited
sUV-induced cyclooxygenase (COX)-2 protein expression in both HaCaT and JB6
cells. COX-2 is a major mediator of skin inflammation. sUV activated the
transcription factors nuclear factor-kappaB and activator protein-1 which, in
turn, induces COX-2 expression. Osajin inhibited transactivation of these
transcription factors. We identified RSK2 as an inhibitory target of osajin by
screening against 68 kinases related to inflammation. Osajin binds with RSK2
directly in an ATP-competitive manner. Computer modeling simulated a plausible
binding orientation between osajin and RSK2. Osajin inhibited sUV-induced
phosphorylation of histone H3, a substrate of RSK2. However, sUV-induced
phosphorylation of extracellular signal-regulated kinases, p38 kinase, c-Jun N
terminal kinase and Akt, which are signaling factors upstream of RSK2, was
unchanged in the presence of osajin. The anti-inflammatory effects and molecular
mechanism of osajin suggest that it may have utility as a functional food for
skin health and cosmetic ingredient. J. Cell. Biochem. 118: 4080-4087, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28409881
TI - 2H->1T Phase Engineering of Layered Tantalum Disulfides in Electrocatalysis:
Oxygen Reduction Reaction.
AB - Tremendous attention is currently being paid to renewable sources of energy.
Transition-metal dichalcogenides (TMDs) have been intensively studied for their
promising catalytic activities in the hydrogen evolution reaction (HER) and the
oxygen reduction reaction (ORR). In this fundamental work, we explored the
catalytic properties of TMD family members 2H TaS2 and 1T TaS2 . Our findings
reveal that both polytypes exhibit poor HER performance, which is even more
pronounced after electrochemical reduction/oxidation. Our experimental data show
that 1T TaS2 has a lower overpotential at a current density of -10 mA cm-1 ,
despite theoretical DFT calculations that indicated that the more favorable free
energy of hydrogen adsorption should make "perfect" 2H TaS2 a better HER
catalyst. Thorough characterization showed that the higher conductivity of 1T
TaS2 and a slightly higher surface oxidation of 2H TaS2 explains this
discrepancy. Moreover, changes in the catalytic activity after electrochemical
treatment are addressed here. For the ORR in an alkaline environment, the
electrochemical treatment led to an improvement in catalytic properties. With
onset potentials similar to that of Pt/C catalysts, TaS2 was found to be an
efficient catalyst for the ORR, rather than for proton reduction, in contrast to
the behavior of Group 6 layered TMDs.
PMID- 28409882
TI - The global burden of childhood cancer: Knowing what we do not know.
PMID- 28409883
TI - Melanocortin 4 Receptor Activation Attenuates Mitochondrial Dysfunction in
Skeletal Muscle of Diabetic Rats.
AB - A previous study has confirmed that the central melanocortin system was able to
mediate skeletal muscle AMP-activated protein kinase (AMPK) activation in mice
fed a high-fat diet, while activation of the AMPK signaling pathway significantly
induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor
(MC4R) was involved in the development of skeletal muscle injury in diabetic
rats. In this study, we treated diabetic rats intracerebroventricularly with MC4R
agonist R027-3225 or antagonist SHU9119, respectively. Then, we measured the
production of reactive oxygen species (ROS), the levels of malondialdehyde (MDA)
and glutathione (GSH), the mitochondrial DNA (mtDNA) content and mitochondrial
biogenesis, and the protein levels of p-AMPK, AMPK, peroxisome proliferator
activated receptor-gamma coactivator 1alpha (PGC-1alpha), sirtuin 1 (SIRT1), and
manganese superoxide dismutase (MnSOD) in the skeletal muscle of diabetic rats.
The results showed that there was significant skeletal muscle injury in the
diabetic rats along with serious oxidative stress and decreased mitochondrial
biogenesis. Treatment with R027-3225 reduced oxidative stress and induced
mitochondrial biogenesis in skeletal muscle, and also activated the AMPK-SIRT1
PGC-1alpha signaling pathway. However, diabetic rats injected with MC4R
antagonist SHU9119 showed an aggravated oxidative stress and mitochondrial
dysfunction in skeletal muscle. In conclusion, our results revealed that MC4R
activation was able to attenuate oxidative stress and mitochondrial dysfunction
in skeletal muscle induced by diabetes partially through activating the AMPK
SIRT1-PGC-1alpha signaling pathway. J. Cell. Biochem. 118: 4072-4079, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28409884
TI - Altered protein expression pattern in colon tissue of mice upon supplementation
with distinct selenium compounds.
AB - The essential trace element selenium (Se) is controversially discussed concerning
its role in health and disease. Its various physiological functions are largely
mediated by Se incorporation in the catalytic center of selenoproteins. In order
to gain insights into the impact of Se deficiency and of supplementation with
different Se compounds (selenite, selenate, selenomethionine) at defined
concentrations (recommended, 150 MUg/kg diet; excessive, 750 MUg/kg diet) in
murine colon tissues, a 20-week feeding experiment was performed followed by
analysis of the protein expression pattern of colon tissue specimens by 2D-DIGE
and MALDI-TOF MS. Using this approach, 24 protein spots were identified to be
significantly regulated by the different Se compounds. These included the
antioxidant enzyme peroxiredoxin-5 (PRDX5), proteins with binding capabilities,
such as cofilin-1 (COF1), calmodulin, and annexin A2 (ANXA2), and proteins
involved in catalytic processes, such as 6-phosphogluconate dehydrogenase (6PGD).
Furthermore, the Se compounds demonstrated a differential impact on the
expression of the identified proteins. Selected target structures were validated
by qPCR and Western blot which mainly confirmed the proteomic profiling data.
Thus, novel Se-regulated proteins in colon tissues have been identified, which
expand our understanding of the physiologic role of Se in colon tissue.
PMID- 28409886
TI - Child and parent preferences for graphical display of patient-reported outcome
data.
AB - Patient-reported outcome measures (PROs) generate reproducible, objective
measures of patient functioning and symptoms. Clinical PRO use has proven
benefits. Parent and child preferences for the graphical display of PRO data are
not known. We conducted a qualitative study to determine preferences for
graphical display of PRO data for use in the clinical setting. Participants were
shown line graphs depicting a patient's PRO score with variations in orientation,
shading and text. Final consensus graphs were elicited. Participants selected the
graph with the highest level of visual and text interpretation of PRO scores.
PMID- 28409885
TI - Long-term results of the transmanubrial osteomuscular-sparing approach for
pediatric tumors.
AB - BACKGROUND: The complete and safe resection of pediatric cervicothoracic tumors,
mostly represented by neurogenic tumors, remains a surgical challenge because of
the complex anatomy of this region. The transmanubrial osteomuscular-sparing
approach (TOSA) is an alternative to isolated or combined cervical and thoracic
approaches enabling the control of supra-aortic vessels and nerves through the
thoracic inlet. METHODS: We retrospectively reviewed the tumor characteristics,
completeness of resection, morbidity, and long-term outcome of patients with
cervicothoracic tumors removed by TOSA between 2000 and 2012 in our institution.
RESULTS: Thirteen patients (7 males, 6 females) underwent surgery at a median age
of 72 months (4-188) for neuroblastoma (n = 6), ganglioneuroblastoma (n = 3),
rhabdoid tumor (n = 1), melanotic schwannoma (n = 1), chordoma (n = 1), and
malignant peripheral nerve sheath tumor in one patient with type 1
neurofibromatosis. The median duration of the procedure was 215 minutes (110
315). Two children presented with postoperative chylothorax that resolved
spontaneously. The median duration of hospitalization was 7 days (4-22). At a
median follow-up of 39 months (2-159), four patients had died of metastatic
relapse (n = 2), locoregional progression (n = 1), and chemotoxicity (n = 1). The
patient with melanotic schwannoma was lost to follow-up after a local relapse at
5 months. Long-term morbidity revealed homolateral Claude-Bernard Horner sign and
upper limb vasomotor dysfunction in disease-free patients due to mandatory
resection of the stellate ganglia. CONCLUSIONS: TOSA is a valuable surgical
approach for all cervicothoracic tumors with acceptable long-term morbidity when
compared with its complexity. We can therefore recommend TOSA for tumors
involving the thoracic inlet.
PMID- 28409888
TI - Reported missing founding member of the International Society of Paediatric
Oncology ...found.
PMID- 28409887
TI - A Blue Diketopyrrolopyrrole Sensitizer with High Efficiency in Nickel-Oxide-based
Dye-Sensitized Solar Cells.
AB - We prepared a series of four new diketopyrrolopyrroles (DPPs)-based sensitizers
that exhibit high-molar extinction coefficients, extended absorption into the
long wavelengths, and well-suited photoredox properties to act as sensitizers in
p-type dye-sensitized solar cells (p-DSSCs). These new DPP dyes, composed of a
thienyl DPP core, are substituted on one end either by a thiophene carboxylic
(Th) or a 4,4'-[(phenyl)aza]dibenzoic acid as anchoring group and, on the other
extremity, either by a proton or a naphthalene diimide (NDI) moiety. These new
dyes were completely characterized by absorption and emission spectroscopy along
with electrochemistry and they were modeled by time-dependent DFT (TD-DFT)
quantum chemical calculations. The photovoltaic study in p-DSSC with iodine-based
electrolyte reveals that the Th-DPP-NDI dye is particularly efficient (Jsc =7.38
mA cm-2 ; Voc =147 mV; FF=0.32; eta=0.35 %) and quite active in the low-energy
region of the solar spectrum (above 700 nm), where only a few NiO dyes are
effective. To illustrate the potential of DPP dyes in photocathodes, we designed
a highly efficient tandem DSSC composed of a TiO2 photoanode sensitized by the
dye D35 and a NiO photocathode sensitized by Th-DPP-NDI. This tandem DSSC gives
the highest performances ever reported (Jsc =6.73 mA cm-2 ; Voc =910 mV; eta=4.1
%) and, importantly, the tandem cell outcompetes with the sub-cells.
PMID- 28409889
TI - Mobilization patterns of children on a hematology/oncology inpatient ward.
AB - BACKGROUND: Children being treated for cancer are admitted to the hospital for
treatment of their disease or complications of therapy. Periods of bed rest
during hospitalization can cause impairments detrimental to children with cancer
who endure many side effects of therapy. Little is known about how these children
mobilize while admitted to the hospital. The purpose of this study was to examine
how children admitted to a hematology/oncology ward are mobilizing and analyze
factors associated with delayed or infrequent mobility. PROCEDURE: A
retrospective chart review was conducted on 228 charts with data recorded on
documented mobilization and referrals to physiotherapy. Primary outcome was
related to mobility including timing, frequency, type, and nature of
mobilization. RESULTS: Almost half of children (43%) mobilized between 3 and 5
days per week, with median time to first mobilization being 2 days (interquartile
range 1-3). Caregivers assisted with mobilization 91% of the time. Children
isolated to their room and those reporting fever had a statistically significant
decrease in the percent of admission days involving mobilization (mean difference
15 and 8%, respectively) than those not isolated and without fever. Children who
were isolated also mobilized 1 day later (P = 0.016) than children who were not
isolated. Percentage of time in isolation was positively correlated with timing
(P = 0.04) and negatively correlated with frequency of mobilization (P < 0.001).
CONCLUSION: Most children admitted to the hospital for treatment of oncologic or
hematologic conditions were noted to mobilize early, but frequency of
mobilization could be improved. Periods of time in isolation appear to negatively
affect mobilization.
PMID- 28409890
TI - Four-State Molecular Shuttling of [2]Rotaxanes in Response to Acid/Base and
Alkali-Metal Cation Stimuli.
AB - In this study, we synthesized [2]rotaxanes possessing three recognition sites-a
dialkylammonium, an alkylarylamine, and a tetra(ethylene glycol) stations-in
their dumbbell-like axle component and dibenzo[24]crown-8 (DB24C8) as their
macrocyclic component. These [2]rotaxanes behaved as four-state molecular
shuttles: i) under acidic conditions, the DB24C8 unit encircled both the
dialkylammonium and alkylarylammonium stations; ii) under neutral conditions, the
dialkylammonium unit was the predominant station for the DB24C8 component; iii)
under basic conditions, when both ammonium centers were deprotonated, the
alkylarylamine unit became a suitable station for the DB24C8 component; and iv)
under basic conditions in the presence of an alkali-metal cation, the
tetra(ethylene glycol) unit recognized the DB24C8 component through cooperative
binding of the alkali-metal ion. In addition, we observed that the [2]rotaxanes
exhibited selective recognition for metal cations. These shuttling motions of the
macrocyclic component proceeded reversibly.
PMID- 28409891
TI - Functional validation of the oncogenic cooperativity and targeting potential of
tuberous sclerosis mutation in medulloblastoma using a MYC-amplified model cell
line.
AB - Medulloblastoma is the most common malignant brain tumor of childhood. To
identify targetable vulnerabilities, we employed inhibitor screening that
revealed mTOR inhibitor hypersensitivity in the MYC-overexpressing
medulloblastoma cell line, D341. Concomitant exome sequencing unveiled an
uncharacterized missense mutation, TSC2A415V , in these cells. We biochemically
demonstrate that the TSC2A415V mutation is functionally deleterious, leading to
shortened half-life and proteasome-mediated protein degradation. These data
suggest that MYC cooperates with activated kinase pathways, enabling
pharmacologic intervention in these treatment refractory tumors. We propose that
identification of activated kinase pathways may allow for tailoring targeted
therapy to improve survival and treatment-related morbidity in medulloblastoma.
PMID- 28409892
TI - Failure of MIBG scan to detect metastases in SDHB-mutated pediatric metastatic
pheochromocytoma.
AB - 123 I-meta-iodo benzyl guanidine (MIBG) scans are considered the gold standard
imaging in neuroblastoma; however, flouro deoxy glucose positron emission
tomography (FDG-PET) scans have increased sensitivity in adults with
pheochromocytoma/paraganglioma. We describe a pediatric patient initially
considered to have localized neuroblastoma based on anatomical imaging and 123 I
MIBG scan, but subsequent investigations revealed germline succinate
dehydrogenase complex iron sulfur subunit B (SDHB) mutation-associated
pheochromocytoma with multiple FDG-avid skeletal metastases. We then compared 123
I-MIBG and FDG-PET scans in children with metastatic
pheochromocytoma/paraganglioma. FDG-PET was superior to 123 I-MIBG scan for the
detection of skeletal metastases (median number of skeletal lesions detected 10
[range 1-30] vs. 2 [range 1-26], respectively; P = 0.005 by t-test). FDG-PET
should be considered the functional scan of choice in children with
pheochromocytoma/paraganglioma.
PMID- 28409895
TI - Editorial: Arthritis Pain: Moving Between Early- and Late-Stage Disease.
PMID- 28409894
TI - Genomic Responses of Mouse Synovial Fibroblasts During Tumor Necrosis Factor
Driven Arthritogenesis Greatly Mimic Those in Human Rheumatoid Arthritis.
AB - OBJECTIVE: Aberrant activation of synovial fibroblasts is a key determinant in
the pathogenesis of rheumatoid arthritis (RA). The aims of this study were to
produce a map of gene expression and epigenetic changes occurring in this cell
type during disease progression in the human tumor necrosis factor (TNF)
transgenic model of arthritis and to identify commonalities with human synovial
fibroblasts. METHODS: We used deep sequencing to probe the transcriptome, the
methylome, and the chromatin landscape of cultured mouse arthritogenic synovial
fibroblasts at 3 stages of disease, as well as synovial fibroblasts stimulated
with human TNF. We performed bioinformatics analyses at the gene, pathway, and
network levels, compared mouse and human data, and validated selected genes in
both species. RESULTS: We found that synovial fibroblast arthritogenicity was
reflected in distinct dynamic patterns of transcriptional dysregulation, which
was especially enriched in pathways of the innate immune response and mesenchymal
differentiation. A functionally representative subset of these changes was
associated with methylation, mostly in gene bodies. The arthritogenic state
involved highly active promoters, which were marked by histone H3K4
trimethylation. There was significant overlap between the mouse and human data at
the level of dysregulated genes and to an even greater extent at the level of
pathways. CONCLUSION: This study is the first systematic examination of the
pathogenic changes that occur in mouse synovial fibroblasts during progressive
TNF-driven arthritogenesis. Significant correlations with the respective human RA
synovial fibroblast data further validate the human TNF-transgenic mouse as a
reliable model of the human disease. The resource of data generated in this work
may serve as a framework for the discovery of novel pathogenic mechanisms and
disease biomarkers.
PMID- 28409893
TI - Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence
to Date.
AB - Migraine, a common neurovascular brain disorder, represents a severe and
widespread health problem; along with medication-induced (medication-overuse)
headache, it is the third-leading cause of disability worldwide. Currently, its
therapeutic management remains unsatisfactory for several reasons; up to 40% of
migraineurs are eligible for prophylactic treatment, but there are issues of
efficacy, safety, and adherence. In recent years the evidence on the role of
calcitonin gene-related peptide (CGRP) in migraine pathophysiology has been
consolidated, so new and promising treatments for migraine pain and its possible
prevention have been developed. The following review reports the results of the
clinical trials conducted so far with each of the new monoclonal antibodies
targeting CGRP or its receptor, with particular reference to safety, tolerance,
and efficacy in migraine prevention. Moreover, the pharmacological
characterization and further developments of each monoclonal antibody are
reported, based on current knowledge.
PMID- 28409896
TI - Childhood osteosarcoma: Incidence and survival in Argentina. Report from the
National Pediatric Cancer Registry, ROHA Network 2000-2013.
AB - BACKGROUND: Differences in incidence and survival in osteosarcoma reports are
considerable worldwide. PURPOSE: This study describes the incidence and survival
of patients with osteosarcoma in Argentina with data from the National Pediatric
Cancer Registry (ROHA), and the impact of age, gender, stage, regional, and
socioeconomic indicators on outcome. METHODS: Pediatric patients with
osteosarcoma reported to ROHA from 2000 through 2013 were analyzed, the annual
age-standardized incidence rate (ASR) was calculated using the National Vital
Statistics, and survival was estimated. The extended human development index
(EHDI) for each reporting region was used as an indicator of socioeconomic
status. RESULTS: There were 515 cases of osteosarcoma identified, yielding an ASR
of 3.2/1,000,000 children (0-14 years old). The ASR did not vary significantly by
year of diagnosis but ranged from 4.0/1,000,000 in the Cuyo/Western Central
region to 2.7/1,000,000 in the northeast region (P < 0.000). The estimated 5-year
survival rate was 45% (95% confidence interval [CI] 44-51%), with no difference
by sex, diagnosis year, region, or EHDI score (P > 0.1 in all cases). Survival
rate for localized disease was 52% (95% CI 45-57%) and for metastatic 22% (95% CI
15-30%). CONCLUSIONS: In Argentina, ASR of osteosarcoma is similar to that in
high-income countries, but survival is lower in all regions. Future work will
focus on identification and reduction of causes of preventable treatment failure.
PMID- 28409897
TI - Enhancing Lifetime and Efficiency of Organic Solar Cell by Applying an In Situ
Synthesized Low-Crystalline ZnO Layer.
AB - By introducing an in situ synthesized low-crystalline ZnO (LC-ZnO) (amorphous)
layer between the cathode and the active layer of PCPDTBT:CdSe solar cell
{PCPDTBT: poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta [2,1-b:3,4
b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)]}, the device keeps more than 80
and 40 % of its initial lifetime after 180 and 360 days without any
encapsulation, respectively. In this regard, 180 days is the highest lifetime
achieved for polymer-based solar cells with direct configuration. In addition,
the power conversion efficiency (PCE) is improved up to 70 % in the presence of
the LC-ZnO interfacial layer. The LC-ZnO layer is synthesized during polymer
annealing after solution-deposition of the precursor at a low temperature (140
degrees C) and a short time. Highly crystalline ZnO (HC-ZnO) nanoparticles are
also synthesized and applied as an interfacial layer. The results show that the
LC-ZnO is superior to the HC-ZnO in acting as cathode interfacial layer and
moisture scavenger because of the high coverage and surface area provided by the
in situ synthesis method.
PMID- 28409898
TI - Comparing catheter-related bloodstream infections in pediatric and adult cancer
patients.
AB - OBJECTIVE: Central venous catheters (CVCs) are essential to treatment of children
with cancer. There are no studies comparing catheter-related bloodstream
infections (CRBSIs) in pediatric cancer patients to those in adults, although
current guidelines for management of CRBSI do not give separate guidelines for
the pediatric population. In this study, we compared CRBSIs in both the pediatric
and adult cancer population. METHODS: We retrospectively reviewed the electronic
medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD
Anderson Cancer Center between September 2005 and March 2014. RESULTS: We
evaluated 248 patients with CRBSI. There was a significant difference in etiology
of CRBSI between pediatric and adult patients (P = 0.002), with the former having
less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10
vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs.
74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult
patients. Peripheral blood cultures were available in only 43% of pediatric
cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P <
0.0001). CONCLUSION: We found higher rates of Gram-negative organisms in adults
and higher rates of polymicrobial in children. Because of the low rates of
peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could
be challenging in pediatrics. A modified CRBSI definition relying more on
clinical criteria may be warranted.
PMID- 28409899
TI - Brief Report: Genetic Variation of the alpha1 -Antitrypsin Gene Is Associated
With Increased Autoantibody Production in Rheumatoid Arthritis.
AB - OBJECTIVE: To examine the prevalence of alpha1 -antitrypsin deficiency (AATD) in
rheumatoid arthritis (RA), and to determine whether AATD is associated with
higher levels of rheumatoid factor (RF), antinuclear antibodies (ANAs), and anti
citrullinated peptide autoantibodies (ACPAs). METHODS: RF, ANAs, and ACPAs were
measured by standard immunoturbidimetry, immunofluorescence assay, and enzyme
linked immunosorbent assay, respectively. Characterization of AAT phenotypes was
performed by isoelectric focusing and immunofixation. The chi-square test with
Yates' correction and the Mann-Whitney U test were used to assess the prevalence
of alleles associated with AATD in RA and to compare mean antibody titers,
respectively. RESULTS: Of 246 patients with RA, 24 who were heterozygous for AATD
were identified, with no statistically significant difference in the prevalence
of AATD between RA patients and the general population (P = 0.39). A positive
association between heterozygosity for AATD and the production of ACPAs was
observed (P < 0.0001), with increased ACPA titers recorded in the AATD RA cohort
compared with the general population (P = 0.01). CONCLUSION: AAT heterozygous
status in RA is strongly associated with positive ACPAs and may define a distinct
subset of patients with increased disease severity.
PMID- 28409900
TI - Introduction: microbial local adaptation: insights from natural populations,
genomics and experimental evolution.
PMID- 28409901
TI - Comparison of markers predicting litter size in different pig breeds.
AB - To overcome the limitations of conventional analysis of male fertility in animals
and humans, proteomic studies have been performed to develop fertility-related
biomarkers for prognosis and diagnosis of male fertility. However, the studies
were focused on specific species or breeds. Therefore, a study is required to
validate whether fertility-related markers would apply to other breeds in pigs.
In this study, previously developed fertility-related biomarkers from Landrace
were validated to use for prognosis of male fertility in commercially available
breeds. Expression level of eight biomarkers in non-capacitated and capacitated
(C) spermatozoa from Yorkshire and Duroc boars was analyzed. And then, to explore
the validity of these markers for prognosis of male fertility, i.e. litter size,
artificial insemination was performed. Among them, RAB2A (NC) and UQCRC1 (NC)
turned out to be highest efficient markers for Yorkshire. RAB2A (C) was most
efficient marker for Duroc. Average litter size has increased as much as 1.41
live born after prediction using eight fertility-related biomarkers in Yorkshire.
In addition, average 2.52 litter size was increased after prediction using eight
fertility-related biomarkers in Duroc. Average litter sizes were especially
highly increased after prediction of fertility using RAB2A (NC) in Yorkshire
(1.57 piglets) and TPI (NC) in Duroc (3.14 piglets), respectively. As a result,
all biomarkers were significantly correlated with litter size. However, overall
accuracy to predict litter size in three breeds was different in response with
each marker. Average litter size after artificial insemination was also
significantly affected by marker selection. Therefore, this study suggests that
developed fertility-related markers may be used for prognosis and diagnosis of
male fertility irrespective of breed. However, selection of efficient markers for
breeds should be considered to obtain more accurate and efficient outcomes.
PMID- 28409902
TI - Testosterone level and endothelial dysfunction in patients with vasculogenic
erectile dysfunction.
AB - The association between endothelial dysfunction and late onset hypogonadism (LOH)
in patients with vasculogenic erectile dysfunction (ED) is not yet well settled.
Our objective was to assess the association between LOH and endothelial
dysfunction in patients with vasculogenic ED. Throughout 2014-2015 a total of 90
men were enrolled in this cross-sectional observational study. Of them 60
patients with a clinical diagnosis of ED were further subdivided into two equal
groups: patients with vasculogenic ED and LOH (A); patients with vasculogenic ED
and euogonadal (B). Thirty age-matched men with no ED or hypogonadism were
enrolled as control group (C). All patients were subjected to detailed medical
and sexual history, total testosterone (TT), calculated free (FT) and
bioavailable testosterone (BT), flow cytometric evaluation for endothelial
progenitor cells (EPCs) (CD45negative/CD34positive/CD144positive) and endothelial
microparticles (EMPs) (CD45negative/CD144positive/annexin V positive). The mean
age +/- SD of the three groups A, B and C were 51.3 +/- 11.1, 53.6 +/- 10.6 and
48.3 +/- 5 years, respectively, with insignificant age differences (p = 0.089).
The diagnostic criteria of LOH were adapted according to European male aging
study, 2010. The means of TT(ng/mL) were 2.32 +/- 0.21, 6.43 +/- 0.36 and 5.37 +/
0.30 in groups A, B and C, respectively. There were highly significant
differences between group A and groups B and C (p < 0.001 for each). The means of
EPCs were 0.43 +/- 0.070, 0.22 +/- 0.05 and 0.032 +/- 0.013 in groups A, B and C,
respectively. The means of EMPs were 0.15 +/- 0.029, 0.056 +/- .013 and 0.014 +/
0.002 in groups A, B and C, respectively. There were significant differences
between group C and groups A and B (p < 0.05 for each). This study clearly
demonstrated that there is a significant association between LOH and the higher
expression of EPCs and EMPs in patients with vasculogenic ED.
PMID- 28409903
TI - Primary, secondary and compensated hypogonadism: a novel risk stratification for
infertile men.
AB - Recently, the cohort of men from the European Male Ageing Study has been
stratified into different categories distinguishing primary, secondary and
compensated hypogonadism. A similar classification has not yet been applied to
the infertile population. We performed a cross-sectional study enrolling 786
consecutive Caucasian-European infertile men segregated into eugonadal [normal
serum total testosterone (>=3.03 ng/mL) and normal luteinizing hormone (<=9.4
mU/mL)], secondary (low total testosterone, low/normal luteinizing hormone),
primary (low total testosterone, elevated luteinizing hormone) and compensated
hypogonadism (normal total testosterone; elevated luteinizing hormone). In this
cross-sectional study, logistic regression models tested the association between
semen parameters, clinical characteristics and the defined gonadal status.
Eugonadism, secondary, primary and compensated hypogonadism were found in 80, 15,
2, and 3% of men respectively. Secondary hypogonadal men were at highest risk for
obesity [OR (95% CI): 3.48 (1.98-6.01)]. Primary hypogonadal men were those at
highest risk for azoospermia [24.54 (6.39-161.39)] and testicular volume <15 mL
[12.80 (3.40-83.26)]. Compensated had a similar profile to primary hypogonadal
men, while their risk of azoospermia [5.31 (2.25-13.10)] and small testicular
volume [8.04 (3.17-24.66)] was lower. The risk of small testicular volume [1.52
(1.01-2.33)] and azoospermia [1.76 (1.09-2.82)] was increased, although in a
milder fashion, in secondary hypogonadal men as well. Overall, primary and
compensated hypogonadism depicted the worst clinical picture in terms of impaired
fertility. Although not specifically designed for infertile men, European Male
Ageing Study categories might serve as a clinical stratification tool even in
this setting.
PMID- 28409904
TI - Prevalence of varicocoele and its association with body mass index among 39,559
rural men in eastern China: a population-based cross-sectional study.
AB - Varicocoele is a common cause of male infertility. We undertook a population
based cross-sectional study to evaluate the prevalence of varicocoele among rural
men in eastern China and its association with body mass index. A total of 39,559
rural men in six counties in Beijing, Guangdong and Shandong provinces were
recruited from 2011 to 2012. The presence and severity of varicocoele were
measured by physical examinations. Univariate and multivariate logistic
regression models were constructed to assess the association between varicocoele
and body mass index after adjusting for possible confounders. Varicocoele was
diagnosed in 1911 of 39,559 participants with an overall prevalence of 4.83%. The
prevalence of varicocoele was highest in underweight (6.29%) and lowest in obese
patients (3.71%, p < 0.05). The prevalence also decreased as body mass index
increased in all three varicocoele grades. In multivariate logistic regression
analysis after adjusting for region, age, height, occupation, cigarette smoking
and alcohol consumption, body mass index was still inversely and independently
associated with varicocoele (p < 0.001). Compared with normal weight men,
underweight men (OR = 1.34; 95% CI, 1.10-1.63) were more likely to have
varicocoele, whereas overweight men (OR = 0.88; 95% CI, 0.79-0.99) and obese men
(OR = 0.75; 95% CI, 0.58-0.97) were less likely to have varicocoele. This study
revealed that the prevalence of varicocoele was 4.83% among rural men in eastern
China; body mass index was inversely and independently associated with the
presence of varicocoele. Future efforts should be made to validate the risk
factors for varicocoele and strengthen the prevention and treatment of
varicocoele, especially in underweight men.
PMID- 28409905
TI - A call for standardized outcomes in microTESE.
PMID- 28409906
TI - Big clinical problem, big advancement, big questions to still address: the status
of microTESE.
PMID- 28409907
TI - The roles of prostate-specific antigen (PSA) density, prostate volume, and their
zone-adjusted derivatives in predicting prostate cancer in patients with PSA less
than 20.0 ng/mL.
AB - The aim of this study was to develop nomograms for predicting prostate cancer and
its zonal location using prostate-specific antigen density, prostate volume, and
their zone-adjusted derivatives. A total of 928 consecutive patients with
prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal
ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital
between 2011 and 2014, were retrospectively enrolled. The patients were randomly
split into training cohort (70%, n = 650) and validation cohort (30%, n = 278).
Predicting models and the associated nomograms were built using the training
cohort, while the validations of the models were conducted using the validation
cohort. Univariate and multivariate logistic regression was performed. Then, new
nomograms were generated based on multivariate regression coefficients. The
discrimination power and calibration of these nomograms were validated using the
area under the ROC curve (AUC) and the calibration curve. The potential clinical
effects of these models were also tested using decision curve analysis. In total,
285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%)
and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate
cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than
0.75. All nomograms had higher calibration and much better net benefit than the
scenarios in predicting patients with or without different zones prostate cancer.
Prostate-specific antigen density, prostate volume, and their zone-adjusted
derivatives have important roles in detecting prostate cancer and its zonal
location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this
is the first nomogram using these parameters to predict outcomes of 12-core
prostate biopsy. These instruments can help clinicians to increase the accuracy
of prostate cancer screening and to avoid unnecessary prostate biopsy.
PMID- 28409908
TI - Charged Metalloporphyrin Polymers for Cooperative Synthesis of Cyclic Carbonates
from CO2 under Ambient Conditions.
AB - A facile and one-pot synthesis of metalloporphyrin-based ionic porous organic
polymers (M-iPOPs) was performed through a typical Yamamoto-Ullmann coupling
reaction for the first time. We used various characterization techniques to
demonstrate that these strongly polar Al-based materials (Al-iPOP) possessed a
relatively uniform microporosity, good swellable features, and a good CO2 capture
capacity. If we consider the particular physicochemical properties, heterogeneous
Al-iPOP, which bears both a metal active center and halogen anion, acted as a
bifunctional catalyst for the solvent- and additive-free synthesis of cyclic
carbonates from various epoxides and CO2 with an excellent activity and good
recyclability under mild conditions. Interestingly, these CO2 -philic materials
could catalyze the cycloaddition reaction smoothly by using simulated flue gas
(15 % CO2 in N2 , v/v) as a raw material, which indicates that a stable local
microenvironment and polymer swellability might promote the transformation. Thus,
the introduction of polar ionic liquid units into metalloporphyrin-based porous
materials is regarded as a promising new strategy for the chemical conversion of
CO2 .
PMID- 28409909
TI - Macroporous Silica with Thick Framework for Steam-Stable and High-Performance
Poly(ethyleneimine)/Silica CO2 Adsorbent.
AB - Poly(ethyleneimine) (PEI)/silica has been widely studied as a solid adsorbent for
post-combustion CO2 capture. In this work, a highly macroporous silica (MacS),
synthesized by secondary sintering of fumed silica, is compared with various
mesoporous silicas with different pore structures as a support for PEI. The
silicas with large pore diameter and volume enabled high CO2 adsorption kinetics
and capacity, because pore occlusion by the supported PEI was minimized. The
steam stability of the silica structures increased with the silica wall thickness
owing to suppressed framework ripening. The silicas with low steam stability
showed rapid leaching of PEI, which indicated that the PEI squeezed out of the
collapsed silica pores leached more readily. Consequently, MacS that had an extra
large pore volume (1.80 cm3 g-1 ) and pore diameter (56.0 nm), and a thick wall
(>10 nm), showed the most promising CO2 adsorption kinetics and capacity as well
as steam stability.
PMID- 28409911
TI - Our 2016 Cancer Cytopathology Young Investigator.
PMID- 28409912
TI - Efficacy of regimens combining direct acting antiviral agents for hepatitis C
virus recombinant form RF1_2k/1b.
PMID- 28409910
TI - Pathogenicity of two COQ7 mutations and responses to 2,4-dihydroxybenzoate bypass
treatment.
AB - Primary ubiquinone (co-enzyme Q) deficiency results in a wide range of clinical
features due to mitochondrial dysfunction. Here, we analyse and characterize two
mutations in the ubiquinone biosynthetic gene COQ7. One mutation from the only
previously identified patient (V141E), and one (L111P) from a 6-year-old girl who
presents with spasticity and bilateral sensorineural hearing loss. We used
patient fibroblast cell lines and a heterologous expression system to show that
both mutations lead to loss of protein stability and decreased levels of
ubiquinone that correlate with the severity of mitochondrial dysfunction. The
severity of L111P is enhanced by the particular COQ7 polymorphism (T103M) that
the patient carries, but not by a mitochondrial DNA mutation (A1555G) that is
also present in the patient and that has been linked to aminoglycoside-dependent
hearing loss. We analysed treatment with the unnatural biosynthesis precursor 2,4
dihydroxybenzoate (DHB), which can restore ubiquinone synthesis in cells
completely lacking the enzymatic activity of COQ7. We find that the treatment is
not beneficial for every COQ7 mutation and its outcome depends on the extent of
enzyme activity loss.
PMID- 28409913
TI - Editorial: Tumor Necrosis Factor-Transgenic Mice: Close Enough to Human
Epigenetics?
PMID- 28409914
TI - The Chemistry of Thought: The Role of the Measurement Sciences in Brain Research.
PMID- 28409915
TI - Nitrogen and Phosphorus Harvesting from Human Urine Using a Stripping,
Absorption, and Precipitation Process.
AB - Human urine contains significant amounts of N (nitrogen) and P (phosphorus);
therefore it has been successfully used as fertilizer in different crops. But the
use of urine as fertilizer has several constraints, such as, the high cost of
transportation, an unpleasant smell, the risk of pathogens, and pharmaceutical
residue. A combined and improved N stripping and P precipitation technique is
used in this study. In this technique, Ca(OH)2 is used to increase the pH of
urine which converts ammonium into ammonia gas and precipitate P as Ca-P
compound. The ammonia gas is stripped and passed into the sulfuric acid where
ammonium sulfate and hydrogen triammonium disulfate is formed. The experiment was
performed using 700 mL of urine and the pH of the urine was increased above 12.
Our results showed that 85-99% of N and 99% of P (w/w) can be harvested from
urine in 28 h at 40 degrees C and in 32 h at 30 degrees C. The harvested N (13%
N w/w) and P (1.5% P w/w) can be used as mineral fertilizer. The economic
assessment of the technique showed that the extraction of N and P from 1 m3 of
pure urine can make a profit of ?2.25.
PMID- 28409917
TI - Response to Comment on "Activation of Persulfate by Graphitized Nanodiamonds for
Removal of Organic Compounds".
PMID- 28409916
TI - Surfactant-Free Aqueous Synthesis of Novel Ba2GdF7:Yb3+, Er3+@PEG Upconversion
Nanoparticles for in Vivo Trimodality Imaging.
AB - In this work, we developed the surfactant-free aqueous synthesis of novel
polyethylene glycol (PEG) coated Ba2GdF7:Yb3+, Er3+ upconversion nanoparticles
(named as, Ba2GdF7:Yb3+, Er3+@PEG UCNPs) for in vivo multimodality imaging
including upconversion luminescence (UCL), X-ray computed tomography (CT), and T1
weighted magnetic resonance (MR). The as-prepared Ba2GdF7:Yb3+, Er3+@PEG UCNPs
not only present bright UCL and reasonably high CT/MR enhancements but also
exhibit excellent colloidal stability, inappreciable cytotoxicity, and negligible
organ toxicity. In particular, the Ba2GdF7:Yb3+, Er3+@PEG UCNPs emit red UCL with
high intensity in the tumor site after intravenous injection via the tail vein of
a nude mouse. The Ba2GdF7:Yb3+, Er3+@PEG UCNPs as contrast agents exhibit high
performance for in vivo trimodality (UCL/CT/MR) imaging of a tumor during HepG2
tumor-bearing nude mouse experiments.
PMID- 28409918
TI - Comment on "Activation of Persulfate by Graphitized Nanodiamonds for Removal of
Organic Compounds".
PMID- 28409919
TI - Atomic-Layer-Deposition Functionalized Carbonized Mesoporous Wood Fiber for High
Sulfur Loading Lithium Sulfur Batteries.
AB - Lithium-sulfur battery (LSB) as one of the most promising energy storage devices
suffers from poor conductivity of sulfur and fast capacity decay triggered by the
dissolution of polysulfides. In this work, functionalized carbonized mesoporous
wood fiber (f-CMWF) is employed as a host to accommodate sulfur for the first
time. Natural wood microfiber has unique hierarchical and mesoporous structure,
which is well-maintained after carbonization. With such a hierarchical mesoporous
structure, a high sulfur loading of 76 wt % is achieved in CMWF electrodes. The
pore size of CMWF is tunable by atomic layer deposition (ALD) of a 5 nm Al2O3
coating to form the f-CMWF. Such a thin layer slightly decreases the sulfur
loading to 70%, but it remarkably promotes the cyclic stability of sulfur
cathode, which delivers an initial capacity of 1115 mAh g-1, and maintains a
reversible capacity of 859 mAh g-1 for 450 cycles, corresponding to a slow
capacity decay rate of 0.046% per cycle. More importantly, natural wood
microfiber is first used as a raw material for sulfur encapsulating. This work is
also critical for using low cost and mesoporous biomass carbon as bifunctional
scaffold for LSB.
PMID- 28409920
TI - Enhanced Photocatalytic Removal of Uranium(VI) from Aqueous Solution by Magnetic
TiO2/Fe3O4 and Its Graphene Composite.
AB - The separation and recovery of uranium from radioactive wastewater is important
from the standpoints of environmental protection and uranium reuse. In the
present work, magnetically collectable TiO2/Fe3O4 and its graphene composites
were fabricated and utilized for the photocatalytical removal of U(VI) from
aqueous solutions. It was found that, under ultraviolet (UV) irradiation, the
photoreactivity of TiO2/Fe3O4 for the reduction of U(VI) was 19.3 times higher
than that of pure TiO2, which is strongly correlated with the Fe0 and additional
Fe(II) generated from the reduction of Fe3O4 by TiO2 photoelectrons. The effects
of initial uranium concentration, solution pH, ionic strength, the composition of
wastewater, and organic pollutants on the U(VI) removal by TiO2/Fe3O4 were
systematically investigated. The results demonstrated its excellent performance
in the cleanup of uranium contamination. As graphene can efficiently attract the
TiO2 photoelectrons and thus decrease their transfer to Fe3O4, the
photodissolution of Fe3O4 in the TiO2/graphene/Fe3O4 composite can be largely
alleviated compared to that of the TiO2/Fe3O4, rendering this ternary composite a
much higher stability. In addition, scanning electron microscopy (SEM), X-ray
diffraction (XRD), X-ray absorption near edge spectroscopy (XANES), and X-ray
photoelectron spectroscopy (XPS) were used to explore the reaction mechanisms.
PMID- 28409921
TI - Mesenchymal Stem Cell-Seeded Regenerated Silk Fibroin Complex Matrices for Liver
Regeneration in an Animal Model of Acute Liver Failure.
AB - The main limitation of liver transplantation as a treatment for end-stage liver
disease or acute liver failure is the scarcity of liver organ donors. To develop
an alternative therapy for acute liver failure, mesenchymal stem cell (MSC)
seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in
vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived
mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form a
scaffold complex. The RSF-MSC scaffold complex (the experimental group) and neat
RSF scaffolds (the control group) were then placed onto the liver surface of mice
induced by CCl4 and detected after 5, 7, 14, 28, and 60 days. The growth and
distribution of MSCs were tracked using fluorescence microscopy and live small
animal fluorescence. Liver functions were tested using an automatic biochemistry
analyzer. The histological kinetics of RSF complex and liver tissues were
observed using hematoxylin & eosin staining. We found that MSCs exhibited good
biocompatibility with RSF and differentiated to hepatocyte-like cells in vitro.
Liver functions of the mice in the experimental group were significantly improved
than that in the control group. Moreover, angiogenesis and hepatocyte-like cells
were discovered in the RSF scaffolds in an animal model of acute liver failure on
the fifth day and in the second month, respectively. The MSCs-RSF matrices show
an obvious therapeutic ability for injured liver function of mice, which is more
efficient than the neat RSF scaffolds.
PMID- 28409922
TI - Generation of Gaseous ClO2 from Thin Films of Solid NaClO2 by Sequential Exposure
to Ultraviolet Light and Moisture.
AB - We report that thin films of solid sodium chlorite (NaClO2) can be
photochemically activated by irradiation with ultraviolet (UV) light to generate
gaseous chlorine dioxide (ClO2) upon subsequent exposure to moisture. The
limiting role of water in the reaction is evidenced by an increase in yield of
ClO2 with relative humidity of the gas stream passed over the UV-activated salt.
The UV-activated state of the NaClO2 was found to possess a half-life of 48 h,
revealing the presence of long-lived UV activated species that subsequently react
with water to produce gaseous ClO2. The yield of ClO2 was determined to be
proportional to the surface area of NaClO2 particles projected to the incident
illumination, consistent with activation of a ~10 nm-thick layer of NaClO2 at the
surface of the micrometer-sized salt crystals (for an activation wavelength of
254 nm). We also found that the quantity of ClO2 released can be tuned ~10-fold
by varying wavelength of UV irradiation and relative humidity of the gas stream
passed over the UV-activated NaClO2. The UV-activated species were not detectable
by electron paramagnetic resonance spectroscopy, indicating that the activated
intermediate is not an excited triplet state of ClO2-. Additionally, neither X
ray photoelectron spectroscopy, nor Raman spectroscopy, nor attenuated total
reflection infrared spectroscopy revealed the identity of the activated
intermediate species. The ability to preactivate solid phase chlorite salt for
subsequent generation of ClO2 upon exposure to moisture suggests the basis of new
materials and methods that permit triggered release of ClO2 in contexts that use
its disinfectant properties.
PMID- 28409923
TI - The Catalase Activity of Catalase-Peroxidases Is Modulated by Changes in the pKa
of the Distal Histidine.
AB - The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an
associated mobile Arg is essential for catalase activity in catalase-peroxidases.
In addition, acidic residues in the entrance channel, in particular an Asp and a
Glu ~7 and ~15 A, respectively, from the heme, significantly enhance catalase
activity. The mechanism by which these channel carboxylates influence catalase
activity is the focus of this work. Seventeen new variants with fewer and
additional acidic residues have been constructed and characterized structurally
and for enzymatic activity, revealing that their effect on activity is roughly
inversely proportional to their distance from the heme and adduct, suggesting
that the electrostatic potential of the heme cavity may be affected. A discrete
group of protonable residues are contained within a 15 A sphere surrounding the
heme iron, and a computational analysis reveals that the pKa of the distal
His112, alone, is modulated within the pH range of catalase activity by the
remote acidic residues in a pattern consistent with its protonated form having a
key role in the catalase reaction cycle. The electrostatic potential also impacts
the catalatic reaction through its influence on the charged status of the Met-Tyr
Trp adduct.
PMID- 28409924
TI - Use of Multiple Linear Regression Models for Setting Water Quality Criteria for
Copper: A Complementary Approach to the Biotic Ligand Model.
AB - Biotic Ligand Models (BLMs) for metals are widely applied in ecological risk
assessments and in the development of regulatory water quality guidelines in
Europe, and in 2007 the United States Environmental Protection Agency (USEPA)
recommended BLM-based water quality criteria (WQC) for Cu in freshwater. However,
to-date, few states have adopted BLM-based Cu criteria into their water quality
standards on a state-wide basis, which appears to be due to the perception that
the BLM is too complicated or requires too many input variables. Using the
mechanistic BLM framework to first identify key water chemistry parameters that
influence Cu bioavailability, namely dissolved organic carbon (DOC), pH, and
hardness, we developed Cu criteria using the same basic methodology used by the
USEPA to derive hardness-based criteria but with the addition of DOC and pH. As
an initial proof of concept, we developed stepwise multiple linear regression
(MLR) models for species that have been tested over wide ranges of DOC, pH, and
hardness conditions. These models predicted acute Cu toxicity values that were
within a factor of +/-2 in 77% to 97% of tests (5 species had adequate data) and
chronic Cu toxicity values that were within a factor of +/-2 in 92% of tests (1
species had adequate data). This level of accuracy is comparable to the BLM.
Following USEPA guidelines for WQC development, the species data were then
combined to develop a linear model with pooled slopes for each independent
parameter (i.e., DOC, pH, and hardness) and species-specific intercepts using
Analysis of Covariance. The pooled MLR and BLM models predicted species-specific
toxicity with similar precision; adjusted R2 and R2 values ranged from 0.56 to
0.86 and 0.66-0.85, respectively. Graphical exploration of relationships between
predicted and observed toxicity, residuals and observed toxicity, and residuals
and concentrations of key input parameters revealed many similarities and a few
key distinctions between the performances of the two models. The pooled MLR model
was then applied to the species sensitivity distribution to derive acute and
chronic criteria equations similar in form to the USEPA's current hardness-based
criteria equations but with DOC, pH, and hardness as the independent variables.
Overall, the MLR is less responsive to DOC than the BLM across a range of
hardness and pH conditions but more responsive to hardness than the BLM.
Additionally, at low and intermediate hardness, the MLR model is less responsive
than the BLM to pH, but the two models respond comparably at high hardness. The
net effect of these different response profiles is that under many typical water
quality conditions, MLR- and BLM-based criteria are quite comparable. Indeed,
conditions where the two models differ most (high pH/low hardness and low pH/high
hardness) are relatively rare in natural aquatic systems. We suggest that this
MLR-based approach, which includes the mechanistic foundation of the BLM but is
also consistent with widely accepted hardness-dependent WQC in terms of
development and form, may facilitate adoption of updated state-wide Cu criteria
that more accurately account for the parameters influencing Cu bioavailability
than current hardness-based criteria.
PMID- 28409925
TI - Conformational Changes in 5-Methoxyindole: Effects of Thermal, Vibrational, and
Electronic Excitations.
AB - The molecule of 5-methoxyindole (5MOI) may adopt two conformational states, syn
and anti, with respect to the relative orientation of the NH and OCH3 groups. The
structure of monomeric 5MOI was characterized spectroscopically, in mid- and near
infrared domains. The conformational composition of 5MOI could be controlled in
three different ways. Thermally, two conformers of 5MOI could be trapped in xenon
matrixes at 16 K. Upon annealing the xenon matrix to temperatures about 30-40 K,
the higher-energy syn form converted to the ground-state anti conformer.
Vibrational excitations in the near-infrared domain, at the frequency of the
first NH stretching overtone, 6853 cm-1, afforded the inverse conformational
transformation, and a part of the anti conformer was upconverted to the syn form.
Electronic excitations in the UV domain, at 315-310 nm, resulted in a total
consumption of the syn form again, in favor of anti. Upon further irradiations at
308 nm, a partial repopulation of the syn form, at the expense of anti, was
observed. We propose a mechanistic explanation of the observed transformations,
which is based on computations of the vibrational spectra of the two conformers
and also on computations of the ground state S0 and the first excited state S1
potential energy surfaces along the coordinate for conformational isomerization.
The highlights of the present work are the first experimental observation of the
minor syn conformer of 5MOI, evidence of the long-range vibrational energy
transfer resulting in conformational isomerization upon excitation of the NH
stretching overtone, and the possibility of partial conformational control of
5MOI by using electronic excitations.
PMID- 28409926
TI - On-Surface Synthesis of Self-Assembled Monolayers of Benzothiazole Derivatives
Studied by STM and XPS.
AB - On-surface synthesis has gradually become a prevalent approach to constructing
two-dimensional functional monolayers on various substrates. In the present work,
the synthesis of self-assembled monolayers (SAMs) of benzothiazole derivatives
was conducted at the liquid/solid interface for the first time. Two kinds of
nanostructures were achieved on the highly oriented pyrolytic graphite (HOPG)
surface via the condensation reaction between aromatic aldehyde derivatives and 2
aminothiophenol (ATP). The formation of thiazole-based self-assemblies was
revealed by scanning tunneling microscopy (STM) and further confirmed by X-ray
photoelectron spectroscopy (XPS). The successful synthesis of the benzothiazole
derivatives not only extends the scope of on-surface reactions but also can be
applied in designing multifunctional SAMs at the interface.
PMID- 28409927
TI - Complex, Dynamic Behavior of Extremely Asymmetric Di-n-Alkylphosphate-Anion
Aggregates, the Long-Chain Effect and the Role of a Limiting Size: Cryo-TEM,
SANS, and X-Ray Diffraction Studies.
AB - For extremely asymmetric n-hexyl(n-decyl)phosphate (HDeP), n-hexyl(n
dodecyl)phosphate (HDoP), and n-hexyl(n-cetyl)phosphate (HCeP), the effect of the
long-chains on the dynamic behavior of their aggregate structures in water was
examined by cryo-TEM imaging, SANS, and X-ray diffraction techniques. The cryo
TEM images demonstrated the complex and dynamic behavior of the aggregates, and
its dependence on the length of the long-chain. Application of the one
dimensional aggregate theory to the SANS results led to the conclusion that the
existence of a limiting size also depended on the length of the main long
hydrocarbon chain and affected strongly the dynamic behavior of the aggregates,
causing breakage of thread-like micelles or ribbon-like aggregates. The X-ray
diffraction patterns of the lyotropic liquid crystalline samples of HDeP and HCeP
were used to estimate the aggregate structures of this limited size.
PMID- 28409928
TI - Sprouting Droplets Driven by Physical Effects Alone.
AB - Combining a partially miscible three-liquid system with interfacially trapped
silica colloids, we show that small droplets can exhibit dramatic growth
phenomena driven by physical effects alone. The mass dense droplets sprout tubes
which grow vertically upward in a gravitational field and respond to the presence
of other droplets in their path. Two of the liquids in our system are water and
toluene. By varying the third liquid, we are able to relate the growth behavior
to the details of the underlying three-fluid phase diagram and the changes to the
interfacial tension. Additionally, we introduce a pendant drop in the path of our
growing drop. We use this to confirm that growth is driven by the partitioning of
solvents, that exchange of solvents between droplets is chemically selective, and
that the exchange behavior can itself generate further growth phenomena.
PMID- 28409929
TI - Oxidative Deaminations and Deisatinylations of Ugi-Azide and Ugi-3CR Products: A
Two-Step MCR-Oxidation Protocol toward Functionalized alpha-Ketoamides and alpha
Ketotetrazoles.
AB - A new postcondensation multicomponent reaction (MCR) methodology, comprising
oxidative deaminations enabling access to multiple privileged carbonyl-containing
scaffolds in two steps, is described. These protocols allow facile access to
functionalized alpha-ketoamide and alpha-ketotetrazole small-molecule
peptidomimetic-like building blocks from prototypical synthons with two points of
diversity. Incorporation of chalcone and alkynyl moieties with further ring
forming reactions enables access to additional novel heterocyclic ring systems,
including a unique and potentially highly pharmacologically relevant scaffold, a
1,2-selenazol-3(2H)-one.
PMID- 28409930
TI - Ultrathin Nonlinear Metasurface for Optical Image Encoding.
AB - Security of optical information is of great importance in modern society. Many
cryptography techniques based on classical and quantum optics have been widely
explored in the linear optical regime. Nonlinear optical encryption in which
encoding and decoding involve nonlinear frequency conversions represents a new
strategy for securing optical information. Here, we demonstrate that an ultrathin
nonlinear photonic metasurface, consisting of meta-atoms with 3-fold rotational
symmetry, can be used to hide optical images under illumination with a
fundamental wave. However, the hidden image can be read out from second harmonic
generation (SHG) waves. This is achieved by controlling the destructive and
constructive interferences of SHG waves from two neighboring meta-atoms. In
addition, we apply this concept to obtain gray scale SHG imaging. Nonlinear
metasurfaces based on space variant optical interference open new avenues for
multilevel image encryption, anticounterfeiting, and background free image
reconstruction.
PMID- 28409931
TI - 1-(4-[18F]Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine: A Novel
Suitable Radioligand with Low Lipophilicity for Imaging sigma1 Receptors in the
Brain.
AB - We have designed and synthesized novel piperazine compounds with low
lipophilicity as sigma1 receptor ligands. 1-(4-Fluorobenzyl)-4-[(tetrahydrofuran
2-yl)methyl]piperazine (10) possessed a low nanomolar sigma1 receptor affinity
and a high selectivity toward the vesicular acetylcholine transporter (>2000
fold), sigma2 receptors (52-fold), and adenosine A2A, adrenergic alpha2,
cannabinoid CB1, dopamine D1, D2L, gamma-aminobutyric acid A (GABAA), NMDA,
melatonin MT1, MT2, and serotonin 5-HT1 receptors. The corresponding radiotracer
[18F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios
in biodistribution studies in mice. Pretreatment with the selective sigma1
receptor agonist SA4503 significantly reduced the level of accumulation of the
radiotracer in the brain. No radiometabolite of [18F]10 was observed to enter the
brain. Positron emission tomography and magnetic resonance imaging confirmed
suitable kinetics and a high specific binding of [18F]10 to sigma1 receptors in
rat brain. Ex vivo autoradiography showed a reduced level of binding of [18F]10
in the cortex and hippocampus of the senescence-accelerated prone (SAMP8)
compared to that of the senescence-accelerated resistant (SAMR1) mice, indicating
the potential dysfunction of sigma1 receptors in Alzheimer's disease.
PMID- 28409932
TI - Study of Protein Dynamics under Nanoconfinement by Spin-Label ESR: A Case of T4
Lysozyme Protein.
AB - The electron spin resonance (ESR) spectra of spin-labeled proteins are sensitive
to dynamics, but discrimination between the various dynamics is often difficult.
Here, we report an improvement in ESR spectral sensitivity to local backbone
dynamics of a protein by a methodology that performs ESR measurement when the
protein is confined in the nanochannels of a mesoporous material. An extensive
set of ESR data, which includes the spectra of a nitroxide-based side chain from
buried and solvent-exposed sites of a T4 lysozyme (T4L) protein, were obtained
over a range of temperatures, 200-300 K, to explore the dynamics of T4L under
nanoconfinement. Spectra were simulated by performing theoretical fits to the
data using the microscopic ordering with macroscopic disordering model. Two
principle dynamic modes, which differ in mobility and ordering, are required to
account for the spectra at temperatures >240 K. We show that the mobile one
correlates only with the local backbone dynamics of buried sites, whereas the
other reflects the difference in local hydration dynamics between the labeling
sites in T4L. The assignment of the mobile component is supported by the X-ray
crystallography data of T4L. Collectively, this study has demonstrated the
validity of such a methodology for improving ESR sensitivity to buried sites in a
protein.
PMID- 28409933
TI - Benzene C-H Etherification via Photocatalytic Hydrogen-Evolution Cross-Coupling
Reaction.
AB - Aryl ethers can be constructed from the direct coupling between the benzene C-H
bond and the alcohol O-H bond with the evolution of hydrogen via the synergistic
merger of photocatalysis and cobalt catalysis. Utilizing the dual catalyst system
consisting of 3-cyano-1-methylquinolinum photocatalyst and cobaloxime,
intermolecular etherification of arenes with various alcohols and intramolecular
alkoxylation of 3-phenylpropanols with formation of chromanes are accomplished.
These reactions proceed at remarkably mild conditions, and the sole byproduct is
equivalent hydrogen gas.
PMID- 28409934
TI - Diastereoselective Synthesis of Cephalotaxus Esters via Asymmetric Mukaiyama
Aldol Reaction.
AB - We report a protocol for efficient stereoselective installation of the chiral
oxygen-containing tetrasubstituted tertiary carbon stereocenter of the side chain
of cephalotaxus esters by means of highly diastereoselective Mukaiyama aldol
reactions between alpha-keto esters (2) and a (Z)-alpha-chloro ketene silyl
acetal. This protocol permitted synthesis of cephalotaxus esters including six
natural products in good to excellent yields (up to 94%) with high
diastereoselectivities (dr up to 97:3) and could be performed on a multigram
scale.
PMID- 28409935
TI - Assessment of Two Solid Anaerobic Digestate Soil Amendments for Effects on Soil
Quality and Biosolarization Efficacy.
AB - Anaerobic digestion is an organic waste bioconversion process that produces
biofuel and digestates. Digestates have potential to be applied as soil amendment
to improve properties for crop production including phytonutrient content and
pest load. Our objective was to assess the impact of solid anaerobic digestates
on weed seed inactivation and soil quality upon soil biosolarization (a pest
control technique that combines solar heating and amendment-induced microbial
activity). Two solid digestates from thermophilic (TD) and mesophilic (MD)
digesters were tested. The solarized TD-amended samples presented significantly
higher mortality of Brassica nigra (71%, P = 0.032) than its equivalent incubated
at room temperature. However, biosolarization with digestate amendment led to
decreased weed seed mortality in certain treatments. The plant-available water,
total C, and extractable P and K were significantly increased (P < 0.05) in the
incubated amended soils. The results confirm the potential of digestates as
beneficial soil amendments. Further studies are needed to elucidate the impacts
of digestate stability on biosolarization efficacy and soil properties.
PMID- 28409936
TI - Visualizing Strain-Induced Pseudomagnetic Fields in Graphene through an hBN
Magnifying Glass.
AB - Graphene's remarkable properties are inherent to its two-dimensional honeycomb
lattice structure. Its low dimensionality, which makes it possible to rearrange
the atoms by applying an external force, offers the intriguing prospect of
mechanically controlling the electronic properties. In the presence of strain,
graphene develops a pseudomagnetic field (PMF) that reconstructs the band
structure into pseudo Landau levels (PLLs). However, a feasible route to
realizing, characterizing and controlling PMFs is still lacking. Here we report
on a method to generate and characterize PMFs in a graphene membrane supported on
nanopillars. A direct measure of the local strain is achieved by using the
magnifying effect of the moire pattern formed against a hexagonal boron nitride
substrate under scanning tunneling microscopy. We quantify the strain-induced PMF
through the PLLs spectra observed in scanning tunneling spectroscopy. This work
provides a pathway to strain induced engineering and electro-mechanical graphene
based devices.
PMID- 28409937
TI - Spatial and Temporal Localization of Flavonoid Metabolites in Strawberry Fruit
(Fragaria * ananassa).
AB - Flavonoids are important metabolites in strawberries (Fragaria * ananassa)
because they accomplish an extensive collection of physiological functions and
are valuable for human health. However, their localization within the fruit
tissue has not been extensively explored. Matrix-assisted laser
desorption/ionization mass spectrometric imaging (MALDI-MSI) was employed to shed
light on the spatial distribution of flavonoids during fruit development. One
wild-type (WT) and two transgenic lines were compared, wherein the transgenic
enzymes anthocyanidin reductase (ANRi) and flavonol synthase (FLSi),
respectively, were down-regulated using an RNAi-based silencing approach. In most
cases, fruit development led to a reduction of the investigated flavonoids in the
fruit tissue; as a consequence, they were exclusively present in the skin of
mature red fruits. In the case of (epi)catechin dimer, both the ANRi and the WT
phenotypes revealed low levels in mature red fruits, whereas the ANRi line bore
the lowest relative concentration, as analyzed by liquid chromatography
electrospray ionization multiple-step mass spectrometry (LC-ESI-MSn).
PMID- 28409938
TI - Molting Materials: Restoring Superhydrophobicity after Severe Damage via
Snakeskin-like Shedding.
AB - The nanostructures that are required to generate superhydrophobic surfaces are
always sensitive to shear and are easily damaged, especially by scratching with
sharp objects. As a result of this destruction, the water repellency will be
lost. We introduce a novel approach to restoring the original surface properties
after mechanical damage. In this approach, the damaged layer is shed like the
skin of a snake. This is demonstrated with a three-layer stack as a proof-of
principle system: when the original, superhydrophobic surface layer is damaged,
this leads to the dissolution of a sacrificial layer below it. Thus, the damaged
layer is shed, a new unscathed surface is uncovered, and superhydrophobicity can
easily be restored after a short washing.
PMID- 28409939
TI - Band-Resolved Double Photoemission Spectroscopy on Correlated Valence Electron
Pairs in Metals.
AB - Correlated valence electrons in Ag and Cu are investigated using double
photoemission spectroscopy driven by a high-order harmonic light source. Electron
pairs consisting of two d electrons as well as pairs with one sp and one d
electron are resolved in the two-dimensional energy spectrum. Surprisingly, the
intensity ratio of sp-d to d-d pairs from Ag is 3 times higher than in the self
convoluted density of states. Our results directly show the band-resolved
configurations of electron pairs in solids and emphasize a band-dependent picture
for electron correlation even in these paradigmatic metals.
PMID- 28409940
TI - Scaling Theory for the Frictionless Unjamming Transition.
AB - We develop a scaling theory of the unjamming transition of soft frictionless
disks in two dimensions by defining local areas, which can be uniquely assigned
to each contact. These serve to define local order parameters, whose distribution
exhibits divergences as the unjamming transition is approached. We derive scaling
forms for these divergences from a mean-field approach that treats the local
areas as noninteracting entities, and demonstrate that these results agree
remarkably well with numerical simulations. We find that the asymptotic behavior
of the scaling functions arises from the geometrical structure of the packing
while the overall scaling with the compression energy depends on the force law.
We use the scaling forms of the distributions to determine the scaling of the
total grain area A_{G} and the total number of contacts N_{C}.
PMID- 28409941
TI - Arbitrarily Accurate Pulse Sequences for Robust Dynamical Decoupling.
AB - We introduce universally robust sequences for dynamical decoupling, which
simultaneously compensate pulse imperfections and the detrimental effect of a
dephasing environment to an arbitrary order, work with any pulse shape, and
improve performance for any initial condition. Moreover, the number of pulses in
a sequence grows only linearly with the order of error compensation. Our
sequences outperform the state-of-the-art robust sequences for dynamical
decoupling. Beyond the theoretical proposal, we also present convincing
experimental data for dynamical decoupling of atomic coherences in a solid-state
optical memory.
PMID- 28409942
TI - Breakdown of String Perturbation Theory for Many External Particles.
AB - We consider massless string scattering amplitudes in a limit where the number of
external particles becomes very large, while the energy of each particle remains
small. Using the growth of the volume of the relevant moduli space, and by means
of independent numerical evidence, we argue that string perturbation theory
breaks down in this limit. We discuss some remarkable implications for the
information paradox.
PMID- 28409943
TI - Probing the Scale Invariance of the Inflationary Power Spectrum in Expanding
Quasi-Two-Dimensional Dipolar Condensates.
AB - We consider an analogue de Sitter cosmos in an expanding quasi-two-dimensional
Bose-Einstein condensate with dominant dipole-dipole interactions between the
atoms or molecules in the ultracold gas. It is demonstrated that a hallmark
signature of inflationary cosmology, the scale invariance of the power spectrum
of inflaton field correlations, experiences strong modifications when, at the
initial stage of expansion, the excitation spectrum displays a roton minimum.
Dipolar quantum gases thus furnish a viable laboratory tool to experimentally
investigate, with well-defined and controllable initial conditions, whether
primordial oscillation spectra deviating from Lorentz invariance at trans
Planckian momenta violate standard predictions of inflationary cosmology.
PMID- 28409944
TI - Coherent Atom-Phonon Interaction through Mode Field Coupling in Hybrid
Optomechanical Systems.
AB - We propose a novel type of optomechanical coupling which enables a tripartite
interaction between a quantum emitter, an optical mode, and a macroscopic
mechanical oscillator. The interaction uses a mechanism we term mode field
coupling: a mechanical displacement modifies the spatial distribution of the
optical mode field, which, in turn, modulates the emitter-photon coupling rate.
In properly designed multimode optomechanical systems, we can achieve situations
in which mode field coupling is the only possible interaction pathway for the
system. This enables, for example, swapping of a single excitation between
emitter and phonon, creation of nonclassical states of motion, and mechanical
ground-state cooling in the bad-cavity regime. Importantly, the emitter-phonon
coupling rate can be enhanced through an optical drive field, allowing active
control of the emitter-phonon coupling for realistic experimental parameters.
PMID- 28409945
TI - Chained Bell Inequality Experiment with High-Efficiency Measurements.
AB - We report correlation measurements on two ^{9}Be^{+} ions that violate a chained
Bell inequality obeyed by any local-realistic theory. The correlations can be
modeled as derived from a mixture of a local-realistic probabilistic distribution
and a distribution that violates the inequality. A statistical framework is
formulated to quantify the local-realistic fraction allowable in the observed
distribution without the fair-sampling or independent-and-identical-distributions
assumptions. We exclude models of our experiment whose local-realistic fraction
is above 0.327 at the 95% confidence level. This bound is significantly lower
than 0.586, the minimum fraction derived from a perfect Clauser-Horne-Shimony
Holt inequality experiment. Furthermore, our data provide a device-independent
certification of the deterministically created Bell states.
PMID- 28409946
TI - Geometric Baryogenesis from Shift Symmetry.
AB - We present a new scenario for generating the baryon asymmetry of the Universe
that is induced by a Nambu-Goldstone (NG) boson. The shift symmetry naturally
controls the operators in the theory while allowing the NG boson to couple to the
spacetime geometry as well as to the baryons. The cosmological background thus
sources a coherent motion of the NG boson, which leads to baryogenesis. Good
candidates of the baryon-generating NG boson are the QCD axion and axionlike
fields. In these cases, the axion induces baryogenesis in the early Universe and
can also serve as dark matter in the late Universe.
PMID- 28409947
TI - Spontaneous Photon Production in Time-Dependent Epsilon-Near-Zero Materials.
AB - Quantum field theory predicts that a spatially homogeneous but temporally varying
medium will excite photon pairs out of the vacuum state. However, this important
theoretical prediction lacks experimental verification due to the difficulty in
attaining the required nonadiabatic and large amplitude changes in the medium.
Recent work has shown that in epsilon-near-zero (ENZ) materials it is possible to
optically induce changes of the refractive index of the order of unity, in
femtosecond time scales. By studying the quantum field theory of a spatially
homogeneous, time-varying ENZ medium, we theoretically predict photon-pair
production that is up to several orders of magnitude larger than in non-ENZ time
varying materials. We also find that while in standard materials the emission
spectrum depends on the time scale of the perturbation, in ENZ materials the
emission is always peaked at the ENZ wavelength. These studies pave the way to
technologically feasible observation of photon-pair emission from a time-varying
background with implications for quantum field theories beyond condensed matter
systems and with potential applications as a new source of entangled light.
PMID- 28409948
TI - Observation of Quantum-Limited Spin Transport in Strongly Interacting Two
Dimensional Fermi Gases.
AB - We measure the transport properties of two-dimensional ultracold Fermi gases
during transverse demagnetization in a magnetic field gradient. Using a phase
coherent spin-echo sequence, we are able to distinguish bare spin diffusion from
the Leggett-Rice effect, in which demagnetization is slowed by the precession of
a spin current around the local magnetization. When the two-dimensional
scattering length is tuned to be comparable to the inverse Fermi wave vector
k_{F}^{-1}, we find that the bare transverse spin diffusivity reaches a minimum
of 1.7(6)h/m, where m is the bare particle mass. The rate of demagnetization is
also reflected in the growth rate of the s-wave contact, observed using time
resolved spectroscopy. The contact rises to 0.28(3)k_{F}^{2} per particle, which
quantifies how scaling symmetry is broken by near-resonant interactions, unlike
in unitary three-dimensional systems. Our observations support the conjecture
that, in systems with strong scattering, the local relaxation rate is bounded
from above by k_{B}T/h.
PMID- 28409949
TI - Publisher's Note: Hydrogen Bonds in Excited State Proton Transfer [Phys. Rev.
Lett. 117, 163002 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.117.163002.
PMID- 28409950
TI - Boson Sampling with Single-Photon Fock States from a Bright Solid-State Source.
AB - A boson-sampling device is a quantum machine expected to perform tasks
intractable for a classical computer, yet requiring minimal nonclassical
resources as compared to full-scale quantum computers. Photonic implementations
to date employed sources based on inefficient processes that only simulate
heralded single-photon statistics when strongly reducing emission probabilities.
Boson sampling with only single-photon input has thus never been realized. Here,
we report on a boson-sampling device operated with a bright solid-state source of
single-photon Fock states with high photon-number purity: the emission from an
efficient and deterministic quantum dot-micropillar system is demultiplexed into
three partially indistinguishable single photons, with a single-photon purity 1
g^{(2)}(0) of 0.990+/-0.001, interfering in a linear optics network. Our
demultiplexed source is between 1 and 2 orders of magnitude more efficient than
current heralded multiphoton sources based on spontaneous parametric down
conversion, allowing us to complete the boson-sampling experiment faster than
previous equivalent implementations.
PMID- 28409951
TI - Electron Number-Based Phase Diagram of Pr_{1-x}LaCe_{x}CuO_{4-delta} and Possible
Absence of Disparity between Electron- and Hole-Doped Cuprate Phase Diagrams.
AB - We performed annealing and angle resolved photoemission spectroscopy studies on
electron-doped cuprate Pr_{1-x}LaCe_{x}CuO_{4-delta} (PLCCO). It is found that
the optimal annealing condition is dependent on the Ce content x. The electron
number (n) is estimated from the experimentally obtained Fermi surface volume for
x=0.10, 0.15 and 0.18 samples. It clearly shows a significant and annealing
dependent deviation from the nominal x. In addition, we observe that the pseudo
gap at hot spots is also closely correlated with n; the pseudogap gradually
closes as n increases. We established a new phase diagram of PLCCO as a function
of n. Different from the x-based one, the new phase diagram shows similar
antiferromagnetic and superconducting phases to those of hole doped ones. Our
results raise a possibility for absence of disparity between the phase diagrams
of electron- and hole-doped cuprates.
PMID- 28409952
TI - Nonsymmetric Interactions Trigger Collective Swings in Globally Ordered Systems.
AB - Many systems in nature, from ferromagnets to flocks of birds, exhibit ordering
phenomena on the large scale. In condensed matter systems, order is statistically
robust for large enough dimensions, with relative fluctuations due to noise
vanishing with system size. Several biological systems, however, are less stable
and spontaneously change their global state on relatively short time scales. Here
we show that there are two crucial ingredients in these systems that enhance the
effect of noise, leading to collective changes of state on finite time scales and
off-equilibrium behavior: the nonsymmetric nature of interactions between
individuals, and the presence of local heterogeneities in the topology of the
network. Our results might explain what is observed in several living systems and
are consistent with recent experimental data on bird flocks and other animal
groups.
PMID- 28409953
TI - Quantum State Transfer via Noisy Photonic and Phononic Waveguides.
AB - We describe a quantum state transfer protocol, where a quantum state of photons
stored in a first cavity can be faithfully transferred to a second distant cavity
via an infinite 1D waveguide, while being immune to arbitrary noise (e.g.,
thermal noise) injected into the waveguide. We extend the model and protocol to a
cavity QED setup, where atomic ensembles, or single atoms representing quantum
memory, are coupled to a cavity mode. We present a detailed study of sensitivity
to imperfections, and apply a quantum error correction protocol to account for
random losses (or additions) of photons in the waveguide. Our numerical analysis
is enabled by matrix product state techniques to simulate the complete quantum
circuit, which we generalize to include thermal input fields. Our discussion
applies both to photonic and phononic quantum networks.
PMID- 28409954
TI - Direct Probe of Topological Invariants Using Bloch Oscillating Quantum Walks.
AB - The topology of a single-particle band structure plays a fundamental role in
understanding a multitude of physical phenomena. Motivated by the connection
between quantum walks and such topological band structures, we demonstrate that a
simple time-dependent, Bloch-oscillating quantum walk enables the direct
measurement of topological invariants. We consider two classes of one-dimensional
quantum walks and connect the global phase imprinted on the walker with its
refocusing behavior. By disentangling the dynamical and geometric contributions
to this phase, we describe a general strategy to measure the topological
invariant in these quantum walks. As an example, we propose an experimental
protocol in a circuit QED architecture where a superconducting transmon qubit
plays the role of the coin, while the quantum walk takes place in the phase space
of a cavity.
PMID- 28409955
TI - Divergent and Ultrahigh Thermal Conductivity in Millimeter-Long Nanotubes.
AB - Low-dimensional materials could display anomalous thermal conduction that the
thermal conductivity (kappa) diverges with increasing lengths, in ways
inconceivable in any bulk materials. However, previous theoretical or
experimental investigations were plagued with many finite-size effects, rendering
the results either indirect or inconclusive. Indeed, investigations on the
anomalous thermal conduction must demand the sample length to be sufficiently
long so that the phenomena could emerge from unwanted finite-size effects. Here
we report experimental observations that the kappa's of single-wall carbon
nanotubes continuously increase with their lengths over 1 mm, reaching at least
8640 W/mK at room temperature. Remarkably, the anomalous thermal conduction
persists even with the presence of defects, isotopic disorders, impurities, and
surface absorbates. Thus, we demonstrate that the anomalous thermal conduction in
real materials can persist over much longer distances than previously thought.
The finding would open new regimes for wave engineering of heat as well as
manipulating phonons at macroscopic scales.
PMID- 28409956
TI - Nonlocalized Generation of Correlated Photon Pairs in Degenerate Down-Conversion.
AB - The achievement of optimum conversion efficiency in conventional spontaneous
parametric down-conversion requires consideration of quantum processes that
entail multisite electrodynamic coupling, actively taking place within the
conversion material. The physical mechanism, which operates through virtual
photon propagation, provides for photon pairs to be emitted from spatially
separated sites of photon interaction; occasionally pairs are produced in which
each photon emerges from a different point in space. The extent of such
nonlocalized generation is influenced by individual variations in both distance
and phase correlation. Mathematical analysis of the global contributions from
this mechanism provides a quantitative measure for a degree of positional
uncertainty in the origin of down-converted emission.
PMID- 28409957
TI - Background Independence and Duality Invariance in String Theory.
AB - Closed string theory exhibits an O(D,D) duality symmetry on tori, which in double
field theory is manifest before compactification. I prove that to first order in
alpha^{'} there is no manifestly background independent and duality invariant
formulation of bosonic string theory in terms of a metric, b field, and dilaton.
To this end I use O(D,D) invariant second order perturbation theory around flat
space to show that the unique background independent candidate expression for the
gauge algebra at order alpha^{'} is inconsistent with the Jacobi identity. A
background independent formulation exists instead for frame variables subject to
alpha^{'}-deformed frame transformations (generalized Green-Schwarz
transformations). Potential applications for curved backgrounds, as in cosmology,
are discussed.
PMID- 28409958
TI - Pressure-Stabilized Tin Selenide Phase with an Unexpected Stoichiometry and a
Predicted Superconducting State at Low Temperatures.
AB - Tin-selenium binary compounds are important semiconductors that have attracted
much interest for thermoelectric and photovoltaic applications. As tin has a +2
or +4 oxidation state and selenium has an oxidation number of -2, only SnSe and
SnSe_{2} have been observed. In this work, we show that the chemical bonding
between tin and selenium becomes counterintuitive under pressures. Combining
evolutionary algorithms and density functional theory, a novel cubic tin-selenium
compound with an unexpected stoichiometry 3?4 has been predicted and further
synthesized in laser-heated diamond anvil cell experiments. Different from the
conventional SnSe and SnSe_{2} semiconductors, Sn_{3}Se_{4} is predicted to be
metallic and exhibit a superconducting transition at low temperatures. Based on
electron density and Bader charge analysis, we show that Sn_{3}Se_{4} has a mixed
nature of chemical bonds. The successful synthesis of Sn_{3}Se_{4} paves the way
for the discovery of other IV-VI compounds with nonconventional stoichiometries
and novel properties.
PMID- 28409959
TI - Systematic Fuel Cavity Asymmetries in Directly Driven Inertial Confinement Fusion
Implosions.
AB - We present narrow-band self-emission x-ray images from a titanium tracer layer
placed at the fuel-shell interface in 60-laser-beam implosion experiments at the
OMEGA facility. The images are acquired during deceleration with inferred
convergences of ~9-14. Novel here is that a systematically observed asymmetry of
the emission is linked, using full sphere 3D implosion modeling, to performance
limiting low mode asymmetry of the drive.
PMID- 28409960
TI - Diffraction-Induced Bidimensional Talbot Self-Imaging with Full Independent
Period Control.
AB - We predict, formulate, and observe experimentally a generalized version of the
Talbot effect that allows one to create diffraction-induced self-images of a
periodic two-dimensional (2D) waveform with arbitrary control of the image
spatial periods. Through the proposed scheme, the periods of the output self
image are multiples of the input ones by any desired integer or fractional
factor, and they can be controlled independently across each of the two wave
dimensions. The concept involves conditioning the phase profile of the input
periodic wave before free-space diffraction. The wave energy is fundamentally
preserved through the self-imaging process, enabling, for instance, the
possibility of the passive amplification of the periodic patterns in the wave by
a purely diffractive effect, without the use of any active gain.
PMID- 28409961
TI - Lateral Casimir Force on a Rotating Particle near a Planar Surface.
AB - We study the lateral Casimir force experienced by a particle that rotates near a
planar surface. The origin of this force lies in the symmetry breaking induced by
the particle rotation in the vacuum and thermal fluctuations of its dipole
moment, and therefore, in contrast to lateral Casimir forces previously described
in the literature for corrugated surfaces, it exists despite the translational
invariance of the planar surface. Working within the framework of fluctuational
electrodynamics, we derive analytical expressions for the lateral force and
analyze its dependence on the geometrical and material properties of the system.
In particular, we show that the direction of the force can be controlled by
adjusting the particle-surface distance, which may be exploited as a new
mechanism to manipulate nanoscale objects.
PMID- 28409962
TI - Anomalous Nernst Effect in the Dirac Semimetal Cd_{3}As_{2}.
AB - Dirac and Weyl semimetals display a host of novel properties. In Cd_{3}As_{2},
the Dirac nodes lead to a protection mechanism that strongly suppresses
backscattering in a zero magnetic field, resulting in ultrahigh mobility (~10^{7}
cm^{2} V^{-1} s^{-1}). In an applied magnetic field, an anomalous Nernst effect
is predicted to arise from the Berry curvature associated with the Weyl nodes. We
report the observation of a large anomalous Nernst effect in Cd_{3}As_{2}. Both
the anomalous Nernst signal and transport relaxation time tau_{tr} begin to
increase rapidly at ~50 K. This suggests a close relation between the protection
mechanism and the anomalous Nernst effect. In a field, the quantum oscillations
of bulk states display a beating effect, suggesting that the Dirac nodes split
into Weyl states, allowing the Berry curvature to be observed as an anomalous
Nernst effect.
PMID- 28409963
TI - Nonsignaling Deterministic Models for Nonlocal Correlations have to be
Uncomputable.
AB - Quantum mechanics postulates random outcomes. However, a model making the same
output predictions but in a deterministic manner would be, in principle,
experimentally indistinguishable from quantum theory. In this work we consider
such models in the context of nonlocality on a device-independent scenario. That
is, we study pairs of nonlocal boxes that produce their outputs
deterministically. It is known that, for these boxes to be nonlocal, at least one
of the boxes' outputs has to depend on the other party's input via some kind of
hidden signaling. We prove that, if the deterministic mechanism is also
algorithmic, there is a protocol that, with the sole knowledge of any upper bound
on the time complexity of such an algorithm, extracts that hidden signaling and
uses it for the communication of information.
PMID- 28409964
TI - Gapless Spin-Liquid Ground State in the S=1/2 Kagome Antiferromagnet.
AB - The defining problem in frustrated quantum magnetism, the ground state of the
nearest-neighbor S=1/2 antiferromagnetic Heisenberg model on the kagome lattice,
has defied all theoretical and numerical methods employed to date. We apply the
formalism of tensor-network states, specifically the method of projected
entangled simplex states, which combines infinite system size with a correct
accounting for multipartite entanglement. By studying the ground-state energy,
the finite magnetic order appearing at finite tensor bond dimensions, and the
effects of a next-nearest-neighbor coupling, we demonstrate that the ground state
is a gapless spin liquid. We discuss the comparison with other numerical studies
and the physical interpretation of this result.
PMID- 28409965
TI - Quantum Backreaction on Three-Dimensional Black Holes and Naked Singularities.
AB - We analytically investigate backreaction by a quantum scalar field on two
rotating Banados-Teitelboim-Zanelli (BTZ) geometries: that of a black hole and
that of a naked singularity. In the former case, we explore the quantum effects
on various regions of relevance for a rotating black hole space-time. We find
that the quantum effects lead to a growth of both the event horizon and the
radius of the ergosphere, and to a reduction of the angular velocity, compared to
the unperturbed values. Furthermore, they give rise to the formation of a
curvature singularity at the Cauchy horizon and show no evidence of the
appearance of a superradiant instability. In the case of a naked singularity, we
find that quantum effects lead to the formation of a horizon that shields it,
thus supporting evidence for the role of quantum mechanics as a cosmic censor in
nature.
PMID- 28409966
TI - Parafermionic Wires at the Interface of Chiral Topological States.
AB - We explore a scenario where local interactions form one-dimensional gapped
interfaces between a pair of distinct chiral two-dimensional topological states
referred to as phases 1 and 2-such that each gapped region terminates at a domain
wall separating the chiral gapless edge states of these phases. We show that this
type of T junction supports pointlike fractionalized excitations obeying
parafermion statistics, thus implying that the one-dimensional gapped interface
forms an effective topological parafermionic wire possessing a nontrivial ground
state degeneracy. The physical properties of the anyon condensate that gives rise
to the gapped interface are investigated. Remarkably, this condensate causes the
gapped interface to behave as a type of anyon "Andreev reflector" in the bulk,
whereby anyons from one phase, upon hitting the interface, can be transformed
into a combination of reflected anyons and outgoing anyons from the other phase.
Thus, we conclude that while different topological orders can be connected via
gapped interfaces, the interfaces are themselves topological.
PMID- 28409967
TI - Quantum Simulation of Single-Qubit Thermometry Using Linear Optics.
AB - Standard thermometry employs the thermalization of a probe with the system of
interest. This approach can be extended by incorporating the possibility of using
the nonequilibrium states of the probe and the presence of coherence. Here, we
illustrate how these concepts apply to the single-qubit thermometer introduced by
Jevtic et al. [Phys. Rev. A 91, 012331 (2015)PLRAAN1050
294710.1103/PhysRevA.91.012331] by performing a simulation of the qubit
environment interaction in a linear-optical device. We discuss the role of the
coherence and how this affects the usefulness of nonequilibrium conditions. The
origin of the observed behavior is traced back to how the coherence affects the
propensity to thermalization. We discuss this aspect by considering the
availability function.
PMID- 28409968
TI - Local Polar Fluctuations in Lead Halide Perovskite Crystals.
AB - Hybrid lead-halide perovskites have emerged as an excellent class of photovoltaic
materials. Recent reports suggest that the organic molecular cation is
responsible for local polar fluctuations that inhibit carrier recombination. We
combine low-frequency Raman scattering with first-principles molecular dynamics
(MD) to study the fundamental nature of these local polar fluctuations. Our
observations of a strong central peak in the cubic phase of both hybrid
(CH_{3}NH_{3}PbBr_{3}) and all-inorganic (CsPbBr_{3}) lead-halide perovskites
show that anharmonic, local polar fluctuations are intrinsic to the general lead
halide perovskite structure, and not unique to the dipolar organic cation. MD
simulations indicate that head-to-head Cs motion coupled to Br face expansion,
occurring on a few hundred femtosecond time scale, drives the local polar
fluctuations in CsPbBr_{3}.
PMID- 28409969
TI - First Benchmark of Relativistic Photoionization Theories against 3D ab initio
Simulation.
AB - Photoelectron spectra and ionization rates encompassing relativistic intensities
and hydrogenlike ions with relativistic binding energies are obtained using a
quasiclassical S-matrix approach. These results, along with those based on the
imaginary time method, are compared with three-dimensional, 1/2-period ab initio
simulations for a wide range of ionization potentials and electric field
amplitudes. Significant differences between the three results are demonstrated.
Time-dependent simulations indicate that the peak ionization current can occur
before the peak of the electric field.
PMID- 28409971
TI - Flow Control of A+B->C Fronts by Radial Injection.
AB - The dynamics of A+B->C fronts is analyzed theoretically in the presence of
passive advection when A is injected radially into B at a constant inlet flow
rate Q. We compute the long-time evolution of the front position, r_{f}, of its
width, w, and of the local production rate R of the product C at r_{f}. We show
that, while advection does not change the well-known scaling exponents of the
evolution of corresponding reaction-diffusion fronts, their dynamics is however
significantly influenced by the injection. In particular, the total amount of
product varies as Q^{-1/2} for a given volume of injected reactant and the front
position as Q^{1/2} for a given time, paving the way to a flow control of the
amount and spatial distribution of the reaction front product. This control
strategy compares well with calcium carbonate precipitation experiments for which
the amount of solid product generated in flow conditions at fixed concentrations
of reactants and the front position can be tuned by varying the flow rate.
PMID- 28409970
TI - Observation of Betatron X-Ray Radiation in a Self-Modulated Laser Wakefield
Accelerator Driven with Picosecond Laser Pulses.
AB - We investigate a new regime for betatron x-ray emission that utilizes kilojoule
class picosecond lasers to drive wakes in plasmas. When such laser pulses with
intensities of ~5*10^{18} W/cm^{2} are focused into plasmas with electron
densities of ~1*10^{19} cm^{-3}, they undergo self-modulation and channeling,
which accelerates electrons up to 200 MeV energies and causes those electrons to
emit x rays. The measured x-ray spectra are fit with a synchrotron spectrum with
a critical energy of 10-20 keV, and 2D particle-in-cell simulations were used to
model the acceleration and radiation of the electrons in our experimental
conditions.
PMID- 28409972
TI - Causality, Nonlocality, and Negative Refraction.
AB - The importance of spatial nonlocality in the description of negative refraction
in electromagnetic materials has been put forward recently. We develop a theory
of negative refraction in homogeneous and isotropic media, based on first
principles, and that includes nonlocality in its full generality. The theory
shows that both dissipation and spatial nonlocality are necessary conditions for
the existence of negative refraction. It also provides a sufficient condition in
materials with weak spatial nonlocality. These fundamental results should have
broad implications in the theoretical and practical analyses of negative
refraction of electromagnetic and other kinds of waves.
PMID- 28409973
TI - Transport Signatures of Quasiparticle Poisoning in a Majorana Island.
AB - We investigate effects of quasiparticle poisoning in a Majorana island with
strong tunnel coupling to normal-metal leads. In addition to the main Coulomb
blockade diamonds, "shadow" diamonds appear, shifted by 1e in gate voltage,
consistent with transport through an excited (poisoned) state of the island.
Comparison to a simple model yields an estimate of parity lifetime for the
strongly coupled island (~1 MUs) and sets a bound for a weakly coupled island
(>10 MUs). Fluctuations in the gate-voltage spacing of Coulomb peaks at high
field, reflecting Majorana hybridization, are enhanced by the reduced lever arm
at strong coupling. When converted from gate voltage to energy units,
fluctuations are consistent with previous measurements.
PMID- 28409974
TI - Picosecond Control of Quantum Dot Laser Emission by Coherent Phonons.
AB - A picosecond acoustic pulse can be used to control the lasing emission from
semiconductor nanostructures by shifting their electronic transitions. When the
active medium, here an ensemble of (In,Ga)As quantum dots, is shifted into or out
of resonance with the cavity mode, a large enhancement or suppression of the
lasing emission can dynamically be achieved. Most interesting, even in the case
when gain medium and cavity mode are in resonance, we observe an enhancement of
the lasing due to shaking by coherent phonons. In order to understand the
interactions of the nonlinearly coupled photon-exciton-phonon subsystems, we
develop a semiclassical model and find an excellent agreement between theory and
experiment.
PMID- 28409975
TI - Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a
Solid-State Single Spin System.
AB - The adiabatic quantum computation is a universal and robust method of quantum
computing. In this architecture, the problem can be solved by adiabatically
evolving the quantum processor from the ground state of a simple initial
Hamiltonian to that of a final one, which encodes the solution of the problem.
Adiabatic quantum computation has been proved to be a compatible candidate for
scalable quantum computation. In this Letter, we report on the experimental
realization of an adiabatic quantum algorithm on a single solid spin system under
ambient conditions. All elements of adiabatic quantum computation, including
initial state preparation, adiabatic evolution (simulated by optimal control),
and final state read-out, are realized experimentally. As an example, we found
the ground state of the problem Hamiltonian S_{z}I_{z} on our adiabatic quantum
processor, which can be mapped to the factorization of 35 into its prime factors
5 and 7.
PMID- 28409976
TI - Many-Particle Dephasing after a Quench.
AB - After a quench in a quantum many-body system, expectation values tend to relax
towards long-time averages. However, temporal fluctuations remain in the long
time limit, and it is crucial to study the suppression of these fluctuations with
increasing system size. The particularly important case of nonintegrable models
has been addressed so far only by numerics and conjectures based on analytical
bounds. In this work, we are able to derive analytical predictions for the
temporal fluctuations in a nonintegrable model (the transverse Ising chain with
extra terms). Our results are based on identifying a dynamical regime of "many
particle dephasing," where quasiparticles do not yet relax but fluctuations are
nonetheless suppressed exponentially by weak integrability breaking.
PMID- 28409977
TI - Hamiltonian for the Zeros of the Riemann Zeta Function.
AB - A Hamiltonian operator H[over ^] is constructed with the property that if the
eigenfunctions obey a suitable boundary condition, then the associated
eigenvalues correspond to the nontrivial zeros of the Riemann zeta function. The
classical limit of H[over ^] is 2xp, which is consistent with the Berry-Keating
conjecture. While H[over ^] is not Hermitian in the conventional sense, iH[over
^] is PT symmetric with a broken PT symmetry, thus allowing for the possibility
that all eigenvalues of H[over ^] are real. A heuristic analysis is presented for
the construction of the metric operator to define an inner-product space, on
which the Hamiltonian is Hermitian. If the analysis presented here can be made
rigorous to show that H[over ^] is manifestly self-adjoint, then this implies
that the Riemann hypothesis holds true.
PMID- 28409978
TI - Erratum: Gravitational Casimir Effect [Phys. Rev. Lett. 114, 081104 (2015)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.114.081104.
PMID- 28409979
TI - Coexistence of Quantum and Classical Flows in Quantum Turbulence in The T=0
Limit.
AB - Tangles of a quantized vortex line of initial density L(0)~6*10^{3} cm^{-2} and
a variable amplitude of fluctuations of flow velocity U(0) at the largest length
scale are generated in superfluid ^{4}He at T=0.17 K, and their free decay L(t)
is measured. If U(0) is small, the excess random component of the vortex line
length first decays as L?t^{-1} until it becomes comparable with the structured
component responsible for the classical velocity field, and the decay changes to
L?t^{-3/2}. The latter regime always ultimately prevails, provided the classical
description of U holds. A quantitative model of coexisting cascades of quantum
and classical energies describes all regimes of the decay.
PMID- 28409980
TI - Nonuniversal Equation of State of the Two-Dimensional Bose Gas.
AB - For a dilute two-dimensional Bose gas the universal equation of state has a
logarithmic dependence on the s-wave scattering length. Here we derive
nonuniversal corrections to this equation of state, taking account of finite
range effects of the interatomic potential. Our beyond-mean-field analytical
results are obtained performing dimensional regularization of divergent zero
point quantum fluctuations within the finite-temperature formalism of functional
integration. In particular, we find that in the grand canonical ensemble the
pressure has a nonpolynomial dependence on the finite- range parameter and it is
a highly nontrivial function of chemical potential and temperature.
PMID- 28409981
TI - Two-Photon Blockade in an Atom-Driven Cavity QED System.
AB - Photon blockade is a dynamical quantum-nonlinear effect in driven systems with an
anharmonic energy ladder. For a single atom strongly coupled to an optical
cavity, we show that atom driving gives a decisively larger optical nonlinearity
than cavity driving. This enhances single-photon blockade and allows for the
implementation of two-photon blockade where the absorption of two photons
suppresses the absorption of further photons. As a signature, we report on three
photon antibunching with simultaneous two-photon bunching observed in the light
emitted from the cavity. Our experiment constitutes a significant step towards
multiphoton quantum-nonlinear optics.
PMID- 28409982
TI - Spin-Liquid-to-Spin-Liquid Transition in Kitaev Magnets Driven by
Fractionalization.
AB - While phase transitions between magnetic analogs of the three states of matter-a
long-range ordered state, paramagnet, and spin liquid-are extensively studied,
the possibility of "liquid-liquid" transitions, namely, between different spin
liquids, remains elusive. By introducing the additional Ising coupling into the
honeycomb Kitaev model with bond asymmetry, we discover that the Kitaev spin
liquid turns into a spin-nematic quantum paramagnet before a magnetic order is
established by the Ising coupling. The quantum phase transition between the two
liquid states accompanies a topological change driven by fractionalized
excitations, the Z_{2} gauge fluxes, and is of first order. At finite
temperatures, this yields a persisting first-order transition line that
terminates at a critical point located deep inside the regime where quantum spins
are fractionalized. It is suggested that similar transitions may occur in other
perturbed Kitaev magnets with bond asymmetry.
PMID- 28409983
TI - Emergence of Compositional Representations in Restricted Boltzmann Machines.
AB - Extracting automatically the complex set of features composing real high
dimensional data is crucial for achieving high performance in machine-learning
tasks. Restricted Boltzmann machines (RBM) are empirically known to be efficient
for this purpose, and to be able to generate distributed and graded
representations of the data. We characterize the structural conditions (sparsity
of the weights, low effective temperature, nonlinearities in the activation
functions of hidden units, and adaptation of fields maintaining the activity in
the visible layer) allowing RBM to operate in such a compositional phase.
Evidence is provided by the replica analysis of an adequate statistical ensemble
of random RBMs and by RBM trained on the handwritten digits data set MNIST.
PMID- 28409984
TI - Omnidirectional Transport in Fully Reconfigurable Two Dimensional Optical
Ratchets.
AB - A fully reconfigurable two-dimensional (2D) rocking ratchet system created with
holographic optical micromanipulation is presented. We can generate optical
potentials with the geometry of any Bravais lattice in 2D and introduce a spatial
asymmetry with arbitrary orientation. Nontrivial directed transport of Brownian
particles along different directions is demonstrated numerically and
experimentally, including on axis, perpendicular, and oblique with respect to an
unbiased ac driving. The most important aspect to define the current direction is
shown to be the asymmetry and not the driving orientation, and yet we show a
system in which the asymmetry orientation of each potential well does not
coincide with the transport direction, suggesting an additional symmetry breaking
as a result of a coupling with the lattice configuration. Our experimental
device, due to its versatility, opens up a new range of possibilities in the
study of nonequilibrium dynamics at the microscopic level.
PMID- 28409985
TI - Gas-Solid Phase Transition in Laser Multiple Filamentation.
AB - While propagating in transparent media, near-infrared multiterawatt (TW) laser
beams break up in a multitude of filaments of typically 100-200 um diameter with
peak intensities as high as 10 to 100 TW/cm^{2}. We observe a phase transition
at incident beam intensities of 0.4 TW/cm^{2}, where the interaction between
filaments induce solidlike two-dimensional crystals with a 2.7 mm lattice
constant, independent of the initial beam diameter. Below 0.4 TW/cm^{2}, we
evidence a mixed phase state in which some filaments are closely packed in
localized clusters, nucleated on inhomogeneities (seeds) in the transverse
intensity profile of the beam, and other are sparse with almost no interaction
with their neighbors, similar to a gas. This analogy with a thermodynamic gas
solid phase transition is confirmed by calculating the interaction Hamiltonian
between neighboring filaments, which takes into account the effect of
diffraction, Kerr self-focusing, and plasma generation. The shape of the
effective potential is close to a Morse potential with an equilibrium bond length
close to the observed value.
PMID- 28409986
TI - Dynamical Crossovers in Prethermal Critical States.
AB - We study the prethermal dynamics of an interacting quantum field theory with an N
component order parameter and O(N) symmetry, suddenly quenched in the vicinity of
a dynamical critical point. Depending on the initial conditions, the evolution of
the order parameter, and of the response and correlation functions, can exhibit a
temporal crossover between universal dynamical scaling regimes governed,
respectively, by a quantum and a classical prethermal fixed point, as well as a
crossover from a Gaussian to a non-Gaussian prethermal dynamical scaling.
Together with a recent experiment, this suggests that quenches may be used in
order to explore the rich variety of dynamical critical points occurring in the
nonequilibrium dynamics of a quantum many-body system. We illustrate this fact by
using a combination of renormalization group techniques and a nonperturbative
large-N limit.
PMID- 28409987
TI - Collective Phenomena Emerging from the Interactions between Dynamical Processes
in Multiplex Networks.
AB - We introduce a framework to intertwine dynamical processes of different nature,
each with its own distinct network topology, using a multilayer network approach.
As an example of collective phenomena emerging from the interactions of multiple
dynamical processes, we study a model where neural dynamics and nutrient
transport are bidirectionally coupled in such a way that the allocation of the
transport process at one layer depends on the degree of synchronization at the
other layer, and vice versa. We show numerically, and we prove analytically, that
the multilayer coupling induces a spontaneous explosive synchronization and a
heterogeneous distribution of allocations, otherwise not present in the two
systems considered separately. Our framework can find application to other cases
where two or more dynamical processes such as synchronization, opinion formation,
information diffusion, or disease spreading, are interacting with each other.
PMID- 28409988
TI - Control of Spatial Correlations between Rydberg Excitations using Rotary Echo.
AB - We manipulate correlations between Rydberg excitations in cold atom samples using
a rotary-echo technique in which the phase of the excitation pulse is flipped at
a selected time during the pulse. The correlations are due to interactions
between the Rydberg atoms. We measure the resulting change in the spatial pair
correlation function of the excitations via direct position-sensitive atom
imaging. For zero detuning of the lasers from the interaction-free Rydberg
excitation resonance, the pair-correlation value at the most likely nearest
neighbor Rydberg-atom distance is substantially enhanced when the phase is
flipped at the middle of the excitation pulse. In this case, the rotary echo
eliminates most uncorrelated (unpaired) atoms, leaving an abundance of correlated
atom pairs at the end of the sequence. In off-resonant cases, a complementary
behavior is observed. We further characterize the effect of the rotary-echo
excitation sequence on the excitation-number statistics.
PMID- 28409989
TI - Superfluid Boundary Layer.
AB - We model the superfluid flow of liquid helium over the rough surface of a wire
(used to experimentally generate turbulence) profiled by atomic force microscopy.
Numerical simulations of the Gross-Pitaevskii equation reveal that the sharpest
features in the surface induce vortex nucleation both intrinsically (due to the
raised local fluid velocity) and extrinsically (providing pinning sites to vortex
lines aligned with the flow). Vortex interactions and reconnections contribute to
form a dense turbulent layer of vortices with a nonclassical average velocity
profile which continually sheds small vortex rings into the bulk. We characterize
this layer for various imposed flows. As boundary layers conventionally arise
from viscous forces, this result opens up new insight into the nature of
superflows.
PMID- 28409991
TI - Spin Superfluidity in Biaxial Antiferromagnetic Insulators.
AB - Antiferromagnets may exhibit spin superfluidity since the dipole interaction is
weak. We seek to establish that this phenomenon occurs in insulators such as NiO,
which is a good spin conductor according to previous studies. We investigate
nonlocal spin transport in a planar antiferromagnetic insulator with a weak
uniaxial anisotropy. The anisotropy hinders spin superfluidity by creating a
substantial threshold that the current must overcome. Nevertheless, we show that
applying a high magnetic field removes this obstacle near the spin-flop
transition of the antiferromagnet. Importantly, the spin superfluidity can then
persist across many micrometers, even in dirty samples.
PMID- 28409990
TI - Memory-Induced Chaos in Cardiac Excitation.
AB - Excitable systems display memory, but how memory affects the excitation dynamics
of such systems remains to be elucidated. Here we use computer simulation of
cardiac action potential models to demonstrate that memory can cause dynamical
instabilities that result in complex excitation dynamics and chaos. We develop an
iterated map model that correctly describes these dynamics and show that memory
converts a monotonic first return map of action potential duration into a
nonmonotonic one, resulting in a period-doubling bifurcation route to chaos.
PMID- 28409992
TI - Correlated Electron Dynamics at Surfaces Investigated via He^{2+} Ion
Neutralization.
AB - The neutralization of a single He^{2+} ion near a Ir surface leads to the
emission of an electron pair. Via coincidence spectroscopy we give evidence that
a sizable amount of these electron pairs originate from a correlated single step
neutralization of the ion involving a total of four electrons from the metal.
These correlated electron pairs cannot be explained in the common picture of two
consecutive and independent neutralization steps. We infer a characteristic time
scale for the correlated electron dynamics in the metal of 40-400 as.
PMID- 28409993
TI - Animal experimentation and alternatives: revealed preferences.
PMID- 28409994
TI - A novel porcine ex vivo retina culture model for oxidative stress induced by
H2O2.
AB - Oxidative stress is a key player in many ophthalmic diseases. However, the role
of oxidative stress in most degenerative processes is not yet known. Therefore,
accurate and practical models are required to efficiently screen for
therapeutics. Porcine eyes are closely related to the human eye, and can be
obtained from the abattoir as a by-product of the food industry. Therefore, they
offer excellent opportunities for the development of culture models with which to
pre-screen potential therapies, while reducing the use of laboratory animals. To
induce oxidative stress, organotypic cultures of porcine retina were treated with
different doses of hydrogen peroxide (H2O2; 100, 300 and 500MUM) for three hours.
On days 3 and 8, the retinas were conserved for histological and Western blotting
analyses and for evaluation of gene expression, which determined the number of
retinal ganglion cells (RGCs), the activation state of glial cells, and the
expression levels of several oxidative stress markers. H2O2 treatment led to a
reduction in the number of RGCs and to an increase in apoptotic RGCs. In
addition, a dose-dependent increase of microglia and an elevation of CD11b
expression was observed. On day 3, a reduction of IL-1beta, and an increase of
iNOS, as well as of HSP70 mRNA were found. On day 8, an increase in TNF-alpha and
IL-1beta mRNA expression was detected. In conclusion, this ex vivo model offers
an opportunity to study the molecular mechanisms underlying certain eye disorders
and to test new therapeutic approaches to diminish the effects of oxidative
stress.
PMID- 28409996
TI - The use of animals in medical research - a historical perspective.
PMID- 28409995
TI - The perception of animal experimentation ethics among Indian teenage school
pupils.
AB - To promote awareness of animal experimentation ethics among teenagers, we created
an educational pamphlet and an accompanying questionnaire. One hundred Indian
teenage school pupils were given the pamphlet and subsequently surveyed with the
questionnaire, to evaluate: a) their perception of animal experimentation ethics;
and b) their opinion on the effectiveness of the pamphlet, according to gender
and school grade/age. There was a significant correlation between grade/age and
support for animal experimentation, i.e. senior students were more inclined to
show support for animal experimentation. There was also a significant correlation
between gender and perception of the need to learn about animal experimentation
ethics, with girls more likely to feel the need to learn about ethics than boys.
In addition, the four questions relating to the usefulness of the pamphlet, and
student satisfaction with its content, received positive responses from the
majority of the students. Even though the pamphlet was concise, it was apparent
that three quarters of the students were satisfied with its content. Gender and
age did not influence this level of satisfaction. Overall, our study shows that
there is a significant correlation between a pupil's school grade/age and their
support for animal experimentation, and that there is also a significant
correlation between gender and the perceived need to learn about animal
experimentation ethics. This pilot scheme involving an educational pamphlet and
questionnaire could be beneficial in helping to formulate basic strategies for
educating teenage school pupils about animal ethics.
PMID- 28409997
TI - Launch of the Alliance for Human Relevant Science.
PMID- 28409998
TI - Suitability of various DNA extraction methods for a traditional Chinese paocai
system.
AB - Traditional paocai brine (PB), which is continuously propagated by back-slopping
and contains various species of lactic acid bacteria (LAB), is critical for the
flavor of paocai. Culture-independent approaches are commonly used to investigate
the microbial communities of fermented food. To evaluate the influence of
different DNA (DNA) extraction methods on estimates of bacterial community
profiles from 4 PBs, the lysis efficiency, DNA yield, purity and denaturing
gradient gel electrophoresis (DGGE) profiles of V3 region of a 16S ribosomal
ribonucleic acid gene were acquired. The cell lysis pattern of SDS + beads and
Lysing matrix E+ beads (methods 3 and 4) showed higher cell lysis efficiency than
SDS and SDS + Lysozyme (methods 1 and 2) in all PBs. SDS + beads obtained the
largest DNA yield of the 4 methods. Moreover, methods 3 and 4 resulted in higher
H' values and generated more global bacteria profiles than other methods.
Overall, our results demonstrate that the properties of PB significantly affect
the efficiency of DNA extraction methods. Methods 3 and 4 were both suitable for
DNA extraction from PB. Method 3 is more economic, simple and rapid than method 4
for large-scale studies of the bacterial profiles of PB.
PMID- 28409999
TI - Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic
retinopathy.
AB - Autophagy plays critical and complex roles in many human diseases, including
diabetes and its complications. However, the role of autophagy in the development
of diabetic retinopathy remains uncertain. Core histone modifications have been
reported involved in the development of diabetic retinopathy, but little is known
about the histone variants. Here, we observed increased autophagy and histone
HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of
type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and
HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG
proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C
overexpression also promotes inflammation and cell toxicity in vitro. Knockdown
of histone HIST1H1C reduces both the basal and stresses (including high glucose)
induced autophagy, and inhibits high glucose induced inflammation and cell
toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the
retinas leads to increased autophagy, inflammation, glial activation and neuron
loss, similar to the pathological changes identified in the early stage of
diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the
retinas of diabetic mice significantly attenuated the diabetes-induced autophagy,
inflammation, glial activation and neuron loss. These results indicate that
histone HIST1H1C may offer a novel therapeutic target for preventing diabetic
retinopathy.
PMID- 28410001
TI - Respiratory Pattern and Tidal Volumes Differ for Pressure Support and Volume
assured Pressure Support in Amyotrophic Lateral Sclerosis.
AB - RATIONALE: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular
disease resulting in respiratory failure and death. Use of noninvasive
ventilation (NIV) improves survival. However, use of volume-assured pressure
support (VAPS) has not been extensively studied in ALS. OBJECTIVES: To explore
the clinical usefulness of a detailed evaluation of device-recorded NIV data in
the management of chronic respiratory failure in ALS, and to determine whether
there are differences in efficacy between patients using VAPS or PS. METHODS: We
performed a retrospective chart review of 271 patients with ALS using either PS
or VAPS, along with an evaluation of device-recorded data to explore differences
in attainment of goal tidal volumes (Vt) and ratio of respiratory rate to tidal
volume (f/Vt), in addition to triggering and cycling ability. RESULTS: Two
hundred and fifteen patients were using PS, while 56 were using VAPS. There were
no significant differences in demographic data, symptoms, pulmonary function, or
patient compliance. Compared with VAPS, achieved Vt was significantly lower for
PS while f/Vt was significantly higher. Percent spontaneous triggering was
relatively preserved in both cohorts, whereas percent spontaneous cycling was
considerably decreased in both. Furthermore, there was no association found
between spontaneous triggering or cycling, and pulmonary function, indicating the
presence of low spontaneous breath cycling or triggering ability is difficult to
predict. CONCLUSIONS: Examination of device data for exhaled tidal volumes and
f/Vt may be of use in evaluating efficacy of NIV in ALS. VAPS provides more
reliable goal Vt than does PS, and is associated with decreased f/Vt. Spontaneous
cycling is decreased in ALS despite preservation of triggering ability. Although
a set backup rate may address decreased triggering, perhaps more importantly,
setting a sufficient fixed inspiratory time would address the issue of decreased
cycling.
PMID- 28410000
TI - Properties of porcine adipose-derived stem cells and their applications in
preclinical models.
AB - Adipose-derived stem cells represent a reliable adult stem cell source thanks to
their abundance, straightforward isolation, and broad differentiation abilities.
Consequently, human adipose-derived stem cells (hASCs) have been used in vitro
for several innovative cellular therapy and regenerative medicine applications.
However, the translation of a novel technology from the laboratory to the clinic
requires first to evaluate its safety, feasibility, and potential efficacy
through preclinical studies in animals. The anatomy and physiology of pigs and
humans are very similar, establishing pigs as an attractive and popular large
animal model for preclinical studies. Knowledge of the properties of porcine
adipose-derived stem cells (pASCs) used in preclinical studies is critical for
their success. While hASCs have been extensively studied this past decade, only a
handful of reports relate to pASCs. The aim of this concise review is to
summarize the current findings about the isolation of pASCs, their culture,
proliferation, and immunophenotype. The differentiation abilities of pASCs and
their applications in porcine preclinical models will also be reported.
PMID- 28410003
TI - Smoking cessation treatment in substance use disorder treatment settings: an
emergency too.
PMID- 28410002
TI - Comparing behavioral health models for reducing risky drinking among older male
veterans.
AB - BACKGROUND: Screening older veterans in Veterans Affairs Medical Center (VAMC)
primary care clinics for risky drinking facilitates early identification and
referral to treatment. OBJECTIVE: This study compared two behavioral health
models, integrated care (a standardized brief alcohol intervention co-located in
primary care clinics) and enhanced referral care (referral to specialty mental
health or substance abuse clinics), for reducing risky drinking among older male
VAMC primary care patients. VAMC variation was also examined. METHOD: A secondary
analysis of longitudinal data from the Primary Care Research in Substance Abuse
and Mental Health for Elderly (PRISM-E) study, a multisite randomized controlled
trial, was conducted with a sample of older male veterans (n = 438) who screened
positive for risky drinking and were randomly assigned to integrated or enhanced
referral care at five VAMCs. RESULTS: Generalized estimating equations revealed
no differences in either behavioral health model for reducing risky drinking at a
6-month follow-up (AOR: 1.46; 95% CI: 0.42-5.07). Older veterans seen at a VAMC
providing geriatric primary care and geriatric evaluation and management teams
had lower odds of risky drinking (AOR: 0.24; 95% CI: 0.07-0.81) than those seen
at a VAMC without geriatric primary care services. CONCLUSIONS: Both integrated
and enhanced referral care reduced risky drinking among older male veterans.
However, VAMCs providing integrated behavioral health and geriatric specialty
care may be more effective in reducing risky drinking than those without these
services. Integrating behavioral health into geriatric primary care may be an
effective public health approach for reducing risky drinking among older
veterans.
PMID- 28410004
TI - RNA in Salivary Extracellular Vesicles as a Possible Tool for Systemic Disease
Diagnosis.
AB - Saliva contains biological information as blood and is recognized as a valuable
diagnostic medium for their noninvasiveness. Although "-omics" researches have
tried to investigate saliva, the origin and significance of its contents are not
clear, and its usage is largely confined to oral disease in the diagnostic and
prognostic field. In an attempt to broaden the applicability of saliva and to
find systemic disease-derived RNA in saliva, we made mouse models that had human
melanoma and isolated extracellular vesicles (EVs) from their saliva by an
aqueous 2-phase system (ATPS), then identified and evaluated their expression of
human melan-A RNA, which is associated with melanoma on skin. With ATPS, EVs were
isolated efficiently and stably while taking less time compared to isolation by
ultracentrifugation. When ATPS was used to isolate EVs from saliva, the mean +/-
SD percentage of EVs recovered from initial EVs was 38.22% +/- 18.55% by the
number of particles, and the mean +/- SD percentage of RNA recovered from the
initial amount was 60.33% +/- 5.34%. RNAs within isolated EVs were analyzed
subsequently by reverse transcription quantitative polymerase chain reaction and
polymerase chain reaction from saliva and plasma. In melanoma mice, amplification
of human melan-A was identified from saliva and plasma, even though a relative
amount of normalized melan-A was lower than that of plasma. These results present
a possibility that RNAs derived from systemic disease are transferred into saliva
from blood in EVs. Also, they suggest that saliva could be exploited in obtaining
information about systemic disease, not only about oral disease, by examining
RNAs in EVs from saliva instead of blood.
PMID- 28410005
TI - Meeting report of the 2016 bone marrow adiposity meeting.
AB - There is considerable interest in the physiology and pathology, as well as the
cellular and molecular biology, of bone marrow adipose tissue (BMAT). Because
bone marrow adiposity is linked not only to systemic energy metabolism, but also
to both bone marrow and musculoskeletal disorders, this biologic compartment has
become of major interest to investigators from diverse disciplines. Bone marrow
adiposity represents a virtual multi-tissue endocrine organ, which encompasses
cells from multiple developmental lineages (e.g., mesenchymal, myeloid, lymphoid)
and occupies all the non-osseous and non-cartilaginous space within long bones. A
number of research groups are now focusing on bone marrow adiposity to understand
a range of clinical afflictions associated with bone marrow disorders and to
consider mechanisms-based strategies for future therapies.
PMID- 28410007
TI - Key roles of Arf small G proteins and biosynthetic trafficking for animal
development.
AB - Although biosynthetic trafficking can function constitutively, it also functions
specifically for certain developmental processes. These processes require either
a large increase to biosynthesis or the biosynthesis and targeted trafficking of
specific players. We review the conserved molecular mechanisms that direct
biosynthetic trafficking, and discuss how their genetic disruption affects animal
development. Specifically, we consider Arf small G proteins, such as Arf1 and
Sar1, and their coat effectors, COPI and COPII, and how these proteins promote
biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of
neuronal dendrites and synapses, extracellular matrix secretion for bone
development, lumen development in epithelial tubes, notochord and neural tube
development, and ciliogenesis. Specific need for the biosynthetic trafficking
system is also evident from conserved CrebA/Creb3-like transcription factors
increasing the expression of secretory machinery during several of these
developmental processes. Moreover, dysfunctional trafficking leads to a range of
developmental syndromes.
PMID- 28410006
TI - Chaperone-mediated autophagy prevents cellular transformation by regulating MYC
proteasomal degradation.
AB - Chaperone-mediated autophagy (CMA), a selective form of protein lysosomal
degradation, is maximally activated in stress situations to ensure maintenance of
cellular homeostasis. CMA activity decreases with age and in several human
chronic disorders, but in contrast, in most cancer cells, CMA is upregulated and
required for tumor growth. However, the role of CMA in malignant transformation
remains unknown. In this study, we demonstrate that CMA inhibition in fibroblasts
augments the efficiency of MYC/c-Myc-driven cellular transformation. CMA blockage
contributes to the increase of total and nuclear MYC, leading to enhancement of
cell proliferation and colony formation. Impaired CMA functionality accentuates
tumorigenesis-related metabolic changes observed upon MYC-transformation.
Although not a direct CMA substrate, we have found that CMA regulates cellular
MYC levels by controlling its proteasomal degradation. CMA promotes MYC
ubiquitination and degradation by regulating the degradation of
C330027C09Rik/KIAA1524/CIP2A (referred to hereafter as CIP2A), responsible for
MYC stabilization. Ubiquitination and proteasomal degradation of MYC requires
dephosphorylation at Ser62, and CIP2A inhibits the phosphatase responsible for
this dephosphorylation. Failure to degrade CIP2A upon CMA blockage leads to
increased levels of phosphorylated MYC (Ser62) and to stabilization of this
oncogene. We demonstrate that this phosphorylation is essential for the CMA
mediated effect, since specific mutation of this site (Ser62 to Ala62) is enough
to normalize MYC levels in CMA-incompetent cells. Altogether these data
demonstrate that CMA mitigates MYC oncogenic activity by promoting its
proteasomal degradation and reveal a novel tumor suppressive role for CMA in
nontumorigenic cells.
PMID- 28410008
TI - Randomized Clinical Trials on Deep Carious Lesions: 5-Year Follow-up.
AB - Deep caries presents a dilemma in terms of which treatment that will render an
optimal prognosis by maintaining pulp vitality with absence of apical pathology.
Previously, 2 randomized clinical trials were performed testing the short-term
effects of stepwise carious tissue removal versus nonselective carious removal to
hard dentin with or without pulp exposure. The aim of this article was to report
the 5-y outcome on these previously treated patients having radiographically well
defined carious lesions extending into the pulpal quarter of the dentin but with
a well-defined radiodense zone between the carious lesion and the pulp. In this
long-term study, 239 of 314 (76.2%) patients were analyzed. The stepwise removal
group had a significantly higher proportion of success (60.2%) at 5-y follow-up
compared with the nonselective carious removal to hard dentin group (46.3%) ( P =
0.031) when pulp exposures per se were included as failures. Pulp exposure rate
was significantly lower in the stepwise carious removal group (21.2% vs. 35.5%; P
= 0.014). Irrespective of pulp exposure status, the difference (13.3%) was still
significant when sustained pulp vitality without apical radiolucency and
unbearable pain was considered (95% confidence interval, 3.1-26.3, P = 0.045).
After pulp exposure, only 9% ( n = 4) of the analyzed patients were assessed as
successful, indicating that the prognosis is highly dubious following
conventional pulp-capping procedures (direct pulp capping or partial pulpotomy)
in deep carious lesions in adults. In conclusion, the stepwise carious removal
group had a significantly higher proportion of pulps with sustained vitality
without apical radiolucency versus nonselective carious removal of deep carious
lesions in adult teeth at 5-y follow-up ( ClinicalTrials.gov NCT00187837 and
NCT00187850).
PMID- 28410009
TI - Studies in the Antrodia serialis group (Polyporales, Basidiomycota).
AB - Taxonomy and phylogeny of the Antrodia serialis group are revised with
morphological, ecological, and geographic data, partial translation elongation
factor 1-alpha (tef1) gene sequences, and nuc rDNA ITS1-5.8S-ITS2-28S sequences.
The group contains 13 species found in boreal and temperate zones of the Northern
Hemisphere. The species are limited to certain geographic areas within Eurasia
and North America. The traditional morphology-based concept of A. serialis covers
at least four closely related species: A. serialis s. str. in Eurasia, A.
angusta, sp. nov., in East Asia, A. serrata, sp. nov., in the American Northeast,
and A. calcitrosa, sp. nov., in the American Northwest. They all are associated
mostly with Picea spp. and show small, but stable morphological differences from
each other. In addition, A. morganii, comb. nov., inhabiting wood of Populus
spp., occurs in North America, and Antrodia alaskana, comb. nov., a large-pored
species, macroscopically similar to A. variiformis, is distributed along the
Pacific coast of North America. The pine-dwelling A. flavimontis, sp. nov.,
similar to A. primaeva from Eurasia, is so far known only from the eastern part
of the Rocky Mountains (Utah and Wyoming).
PMID- 28410010
TI - Phylogeny and diversity of Fomitiporella (Hymenochaetales, Basidiomycota).
AB - Fomitiporella accommodates polypores producing annual to perennial basidiocarps
with an indistinct subiculum (very thin to almost lacking), mostly a dimitic
hyphal structure, lacking any kind of setae, with brownish, thick-walled
basidiospores, and causing a white rot. Previously, only a few samples of
Fomitiporella were studied on the basis of morphological and nuc 28S rDNA (28S)
based phylogenetic analyses. In this study, we made a comprehensive study on
Fomitiporella on the basis of collections from Central America, USA, Europe, and
China. The phylogenetic analysis, including 28 nuc 28S rDNA and 29 nuc rDNA ITS1
5.8S-ITS2 (internal transcribed spacer [ITS]) sequences newly generated,
discovered 14 new lineages. Combined with morphological evidence, 4 new lineages
are described and illustrated as new species, viz., Fomitiporella americana, F.
micropora, F. sinica, and F. subinermis; 10 other new lineages, each with a
single collection, are still treated as unidentified taxa; three new
combinations, viz., Fomitiporella tenuissima, F. chinensis, and F. resupinata,
are proposed. In addition, F. inermis is redescribed. A key to the 12 known
species of Fomitiporella is provided.
PMID- 28410012
TI - Combination of Arginine Depletion and Chemotherapy in Thoracic Malignancies.
PMID- 28410011
TI - Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal
Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic.
AB - Purpose Multidisciplinary management improves complex treatment decision making
in cancer care, but its impact for bladder cancer (BC) has not been documented.
Although radical cystectomy (RC) currently is viewed as the standard of care for
muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing
trimodal therapy (TMT) that combines transurethral resection of bladder tumor,
chemotherapy for radiation sensitization, and external beam radiotherapy has
emerged as a valid treatment option. In the absence of randomized studies, this
study compared the oncologic outcomes between patients treated with RC or TMT by
using a propensity score matched-cohort analysis. Methods Data from patients
treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013
were reviewed retrospectively. Those who received TMT for MIBC were identified
and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status,
Charlson comorbidity score, treatment date, age, carcinoma in situ status, and
hydronephrosis) with propensity scores to patients who underwent RC. Overall
survival and disease-specific survival (DSS) were assessed with Cox proportional
hazards modeling and a competing risk analysis, respectively. Results A total of
112 patients with MIBC were included after matching (56 who had been treated with
TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage
cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths
(35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT
group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC
and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6
(10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC,
TMT yielded survival outcomes similar to those of matched patients who underwent
RC. Appropriately selected patients with MIBC should be offered the opportunity
to discuss various treatment options, including organ-sparing TMT.
PMID- 28410013
TI - Genetic Testing in Patients With Newly Diagnosed Breast Cancer: Room for
Improvement.
PMID- 28410014
TI - Gender Differences in Posttraumatic Stress Disorder Among U.S. Navy Healthcare
Personnel.
AB - BACKGROUND: The role of women in the U.S. military has changed markedly over the
course of 20th- and 21st-century conflicts. Although women frequently occupy
healthcare positions in the military, little is known about gender differences in
posttraumatic stress disorder (PTSD) within this occupational subgroup. MATERIALS
AND METHODS: A total of 4275 (667 women and 3608 men) U.S. Navy healthcare
personnel supporting military operations in Iraq and Afghanistan were identified
from electronic deployment records. Data from Post-Deployment Health Assessments
were abstracted to identify PTSD screen positives, and to adjust for self
reported combat exposure and other deployment experiences. RESULTS: The
prevalence of PTSD screen positive in the sample was 8.2% (n = 351/4275). After
adjusting for combat exposure, previous psychiatric history, and demographics,
women had significantly higher odds of screening positive for PTSD than did men
(odds ratio = 1.99, 95% confidence interval 1.34-2.96). Interactions between
gender and combat exposure, and between gender and previous psychiatric history
were not statistically significant. CONCLUSIONS: This is one of the first studies
to examine gender differences in PTSD among military healthcare personnel. Future
research should account for additional stressors, such as long work hours,
disrupted sleep patterns, and number of casualties treated. As women are further
integrated into military occupations that may lead to different exposures,
knowledge of gender differences in the manifestation of PTSD is paramount for
prevention and treatment purposes.
PMID- 28410017
TI - Abstracts from Women's Health 2017: The 25th Annual Congress April 28-30, 2017
Washington, DC.
PMID- 28410015
TI - Management of Weight Gain in Midlife Women: Hormone Therapy and Beyond.
PMID- 28410018
TI - Assessing the Potential Contributions of Reduced Immigrant Viability and
Fecundity to Reproductive Isolation.
AB - Reduced fitness of immigrants from alternative environments is thought to be an
important reproductive isolating barrier. Most studies evaluating the importance
of the relative fitness of immigrants to speciation have focused on reduced
survival of immigrants (i.e., immigrant inviability). However, variation in
fecundity appears to have a greater impact on variation in fitness than does
variation in viability, suggesting that reduced fecundity of immigrants could act
as an important yet largely overlooked reproductive isolating barrier. Using a
model and a survey of studies of local adaptation, we evaluate the relative
strength of reduced immigrant viability and fecundity as potential causes of
reproductive isolation. We found that reduced fecundity as compared to reduced
viability as a reproductive isolating barrier should increase in importance as
the relative costs of reproduction increase. Consistent with the elevated demands
of reproduction reported in the literature, we found that reproductive isolation
from reduced immigrant fecundity was of similar magnitude or greater than that
from reduced immigrant viability, particularly in the early stages of speciation.
These results suggest that the important role of differential fecundity in local
adaptation extends to speciation.
PMID- 28410020
TI - Honorary Lifetime Membership Award: Robert Ricklefs.
PMID- 28410019
TI - Mating System Evolution under Strong Pollen Limitation: Evidence of Disruptive
Selection through Male and Female Fitness in Clarkia xantiana.
AB - Selection on floral traits in hermaphroditic plants is determined by both male
and female reproductive success. However, predictions regarding floral trait and
mating system evolution are often based solely on female fitness. Selection via
male fitness has the potential to affect the outcomes of floral evolution. In
this study, we used paternity analysis to assess individual selfing rates and
selection on floral traits via male and female fitness in an experimental
population of Clarkia xantiana where pollen limitation of seed set was strong. We
detected selection through both female and male fitness with reinforcing or
noninterfering patterns of selection through the two sex functions. For female
fitness, selection favored reduced herkogamy and protandry, traits that promote
increased autonomous selfing. For male fitness, selection on petal area was
disruptive, with higher trait values conferring greater pollinator attraction and
outcross siring success and smaller trait values leading to higher selfed siring
success. Combining both female and male fitness, selection on petal area and
protandry was disruptive because intermediate phenotypes were less successful as
both males and females. Finally, functional relationships among male and female
fertility components indicated that selfing resulted in seed discounting and
pollen discounting. Under these functional relationships, the evolutionarily
stable selfing rate can be intermediate or predominantly selfing or outcrossing,
depending on the segregating load of deleterious mutations.
PMID- 28410021
TI - Frontispiece (1891).
PMID- 28410022
TI - Intraspecific Competition and Inbreeding Depression: Increased Competitive Effort
by Inbred Males Is Costly to Outbred Opponents.
AB - A recent theoretical model suggests that intraspecific competition is an
important determinant of the severity of inbreeding depression. The reason for
this is that intraspecific competition is density dependent, leading to a
stronger negative effect on inbred individuals if they are weaker competitors
than outbred ones. In support of this prediction, previous empirical work shows
that inbred individuals are weaker competitors than outbred ones and that
intraspecific competition often exacerbates inbreeding depression. Here, we
report an experiment on the burying beetle Nicrophorus vespilloides, in which we
recorded the outcome of competition over a small vertebrate carcass between an
inbred or outbred male resident caring for a brood and a size-matched inbred or
outbred male intruder. We found that inbred males were more successful as
intruders in taking over a carcass from a male resident and were injured more
frequently as either residents or intruders. Furthermore, inbred males gained
less mass during the breeding attempt and had a shorter adult life span than
outbred males. Finally, successful resident males reared a substantially smaller
brood comprised of lighter larvae when the intruder was inbred than when it was
outbred. Our results shows that inbred males increased their competitive effort,
thus contradicting previous work suggesting that inbred males are weaker
competitors. Furthermore, our results shows that inbred intruders impose a
greater cost to resident males, suggesting that outbred individuals can suffer
fitness costs as a result of competition with inbred ones.
PMID- 28410023
TI - Timing of Breeding in an Ecologically Trapped Bird.
AB - In human-modified environments, organisms may prefer to use habitats where their
reproductive performance is lower compared to alternative options. Many such
ecological traps occur in seasonally changing environments. Although the timing
of breeding has been shown to impact reproductive performance in a variety of
organisms, it has never been considered as a potential mechanism underlying
ecological traps. We address this issue with a migratory bird, the red-backed
shrike, breeding in a human-modified, farmland-forest landscape. Shrikes prefer
breeding in forest clear-cuts where their reproductive performance is lower than
in less attractive farmland. We compared brood size and quality of early (first
broods) and delayed breeders (replacement broods) between the two habitats. We
found a stronger seasonal decrease in reproductive performance in preferred
forest clear-cuts than in farmland. Food resources were slightly more abundant in
forest than in farmland at the beginning of the season but depleted more steeply
in forest by the end of the breeding season. By contrast, the phenotypic quality
of breeders did not decline over the course of the season in either habitat. This
is the first report that the timing of breeding relative to the seasonal change
in key resources may play a significant role in explaining low reproductive
performance in ecological traps.
PMID- 28410024
TI - Testing the Terminal Investment Hypothesis in California Oaks.
AB - The terminal investment hypothesis-which proposes that reproductive investment
should increase with age-related declines in reproductive value-has garnered
support in a range of animal species but has not been previously examined in long
lived plants, such as trees. We tested this hypothesis by comparing relative
acorn production and radial growth among 1,000+ mature individuals of eight
species of California oaks (genus Quercus) followed for up to 37 years, during
which time 70 trees died apparently natural deaths. We found no significant
differences in the radial growth, acorn production, or index of reproductive
effort, taking into consideration both growth and reproduction among dying trees
relative to either conspecific trees at the same site that did not die or growth
and reproduction from earlier years for the focal trees that did eventually die.
Furthermore, we found no consistent trade-off between growth and reproduction
among trees that died, nor did dying trees significantly alter their relative
investment in reproduction even as they underwent physical decline. Trees
approaching the end of their lives are often in poor physical condition but do
not appear to differentially invest more of their diminished resources in
reproduction compared with healthy trees.
PMID- 28410025
TI - Fear Mediates Trophic Cascades: Nonconsumptive Effects of Predators Drive Aquatic
Ecosystem Function.
AB - Predators control prey populations and influence communities and the functioning
of ecosystems through a combination of consumptive and nonconsumptive effects.
These effects can be locally confined to one ecosystem but can also be extended
to neighboring ecosystems. In this study, we investigated the nonconsumptive
effects of terrestrial avian predators on the communities of aquatic
invertebrates inhabiting bromeliads and on the functioning of these natural
ecosystems. Bromeliads with stuffed birds placed nearby showed a decrease in
aquatic damselfly larvae abundance and biomass, and we can infer that these
changes were caused by antipredator responses. These larvae, which are top
predators in bromeliad ecosystems, changed the composition of the entire aquatic
invertebrate community. While total species richness, mesopredator richness, and
shredder abundance increased in the presence of birds, scraper biomass decreased,
possibly as a consequence of the increase in mesopredator richness. High scraper
biomass in the absence of birds may have accelerated detrital decomposition,
making more nutrients available for bromeliads, which grew more. These results
show that nonconsumptive effects triggered by terrestrial predators can cascade
down to lower trophic levels and dramatically affect the functioning of aquatic
ecosystems, which can in turn alter nutrient provision to terrestrial ecosystems.
PMID- 28410026
TI - Variation in Growth Drives the Duration of Parental Care: A Test of Ydenberg's
Model.
AB - The duration of parental care in animals varies widely, from none to lifelong.
Such variation is typically thought to represent a trade-off between growth and
safety. Seabirds show wide variation in the age at which offspring leave the
nest, making them ideal to test the idea that a trade-off between high energy
gain at sea and high safety at the nest drives variation in departure age
(Ydenberg's model). To directly test the model assumptions, we attached time
depth recorders to murre parents (fathers [which do all parental care at sea] and
mothers; [Formula: see text] of each). Except for the initial mortality
experienced by chicks departing from the colony, the mortality rate at sea was
similar to the mortality rate at the colony. However, energy gained by the chick
per day was ~2.1 times as high at sea compared with at the colony because the
father spent more time foraging, since he no longer needed to spend time
commuting to and from the colony. Compared with the mother, the father spent ~2.6
times as much time diving per day and dived in lower-quality foraging patches. We
provide a simple model for optimal departure date based on only (1) the
difference in growth rate at sea relative to the colony and (2) the assumption
that transition mortality from one life-history stage to the other is size
dependent. Apparently, large variation in the duration of parental care can arise
simply as a result of variation in energy gain without any trade-off with safety.
PMID- 28410027
TI - How Sex-Biased Dispersal Affects Sexual Conflict over Care.
AB - Existing models of parental investment have mainly focused on interactions at the
level of the family and have paid much less attention to the impact of population
level processes. Here we extend classical models of parental care to assess the
impact of population structure and limited dispersal. We find that sex
differences in dispersal substantially affect the amount of care provided by each
parent, with the more philopatric sex providing the majority of care to young.
This effect is most pronounced in highly viscous populations: in such cases, when
classical models would predict stable biparental care, inclusion of a modest sex
difference in dispersal leads to uniparental care by the philopatric sex. In
addition, mating skew also affects sex differences in parental investment, with
the more numerous sex providing most of the care. However, the effect of mating
skew holds only when parents care for their own offspring. When individuals breed
communally, we recover the previous finding that the more philopatric sex
provides most of the care even when it is the rarer sex. We conclude that sex
biased dispersal is likely to be an important yet currently overlooked driver of
sex differences in parental care.
PMID- 28410028
TI - Perceptual Ranges, Information Gathering, and Foraging Success in Dynamic
Landscapes.
AB - How organisms gather and utilize information about their landscapes is central to
understanding land-use patterns and population distributions. When such
information originates beyond an individual's immediate vicinity, movement
decisions require integrating information out to some perceptual range. Such
nonlocal information, whether obtained visually, acoustically, or via
chemosensation, provides a field of stimuli that guides movement. Classically,
however, models have assumed movement based on purely local information (e.g.,
chemotaxis, step-selection functions). Here we explore how foragers can exploit
nonlocal information to improve their success in dynamic landscapes. Using a
continuous time/continuous space model in which we vary both random (diffusive)
movement and resource-following (advective) movement, we characterize the optimal
perceptual ranges for foragers in dynamic landscapes. Nonlocal information can be
highly beneficial, increasing the spatiotemporal concentration of foragers on
their resources up to twofold compared with movement based on purely local
information. However, nonlocal information is most useful when foragers possess
both high advective movement (allowing them to react to transient resources) and
low diffusive movement (preventing them from drifting away from resource peaks).
Nonlocal information is particularly beneficial in landscapes with sharp (rather
than gradual) patch edges and in landscapes with highly transient resources.
PMID- 28410029
TI - Ecological Pleiotropy Suppresses the Dynamic Feedback Generated by a Rapidly
Changing Trait.
AB - Population dynamics may carry a signature of an ecology-evolution-ecology
feedback, known as eco-evolutionary dynamics, when functionally important traits
change. Given current theory, the absence of a feedback from a trait with strong
links to species interactions should not occur. In a previous study with the
Didinium-Paramecium predator-prey system, however, rapid and large-magnitude
changes in predator cell volume occurred without any noticeable effect on the
population dynamics. Here I resolve this theory-data conflict by showing that
ecological pleiotropy-when a trait has more than one functional effect on an
ecological process-suppresses shifts in dynamics that would arise, given the
links between cell volume and the species interaction. Whether eco-evolutionary
dynamics arise, therefore, depends not just on the ecology-evolution feedback but
on the net effect that a trait has on different parts of the underlying
interaction.
PMID- 28410030
TI - Ecological Release from Aquatic Predation Is Associated with the Emergence of
Marine Blenny Fishes onto Land.
AB - An ecological release from competition or predation is a frequent adaptive
explanation for the colonization of novel environments, but empirical data are
limited. On the island of Rarotonga, several blenny fish species appear to be in
the process of colonizing land. Anecdotal observations have implied that aquatic
predation is an important factor in prompting such amphibious fish behavior. We
provide evidence supporting this hypothesis by demonstrating that amphibious
blennies shift their abundance up and down the shoreline to remain above
predatory fishes that periodically move into intertidal areas during high tide. A
predation experiment using blenny mimics confirmed a high risk of aquatic
predation for blennies, significantly higher than predation experienced on land.
These data suggest that predation has played an active role in promoting
terrestrial activity in amphibious blennies and provide a rare example of how
ecological release from predation could drive the colonization of a novel
environment.
PMID- 28410031
TI - The Ecological Dynamics of Natural Selection: Traits and the Coevolution of
Community Structure.
AB - Natural selection has both genetic and ecological dynamics. The fitnesses of
individuals change with their ecological context, and so the form and strength of
selective agents change with abiotic factors and the phenotypes and abundances of
interacting species. I use standard models of consumer-resource interactions to
explore the ecological dynamics of natural selection and how various trait types
influence these dynamics and the resulting structure of a community of coevolving
species. Evolutionary optima favored by natural selection depend critically on
the abundances of interacting species, and the traits of species can undergo
dynamic cycling in limited areas of parameter space. The ecological dynamics of
natural selection can also drive shifts from one adaptive peak to another, and
these ecologically driven adaptive peak shifts are fundamental to the dynamics of
niche differentiation. Moreover, this ecological differentiation is fostered in
more productive and more benign environments where species interactions are
stronger and where the selection gradients generated by species interactions are
stronger. Finally, community structure resulting from coevolution depends
fundamentally on the types of traits that underlie species interactions. The
ecological dynamics of the process cannot be simplified, neglected, or ignored if
we are to build a predictive theory of natural selection.
PMID- 28410032
TI - Predicting Responses to Contemporary Environmental Change Using Evolutionary
Response Architectures.
AB - Rapid environmental change currently presents a major threat to global
biodiversity and ecosystem functions, and understanding impacts on individual
populations is critical to creating reliable predictions and mitigation plans.
One emerging tool for this goal is high-throughput sequencing technology, which
can now be used to scan the genome for signs of environmental selection in any
species and any system. This explosion of data provides a powerful new window
into the molecular mechanisms of adaptation, and although there has been some
success in using genomic data to predict responses to selection in fields such as
agriculture, thus far genomic data are rarely integrated into predictive
frameworks of future adaptation in natural populations. Here, we review both
theoretical and empirical studies of adaptation to rapid environmental change,
focusing on areas where genomic data are poised to contribute to our ability to
estimate species and population persistence and adaptation. We advocate for the
need to study and model evolutionary response architectures, which integrate
spatial information, fitness estimates, and plasticity with genetic architecture.
Understanding how these factors contribute to adaptive responses is essential in
efforts to predict the responses of species and ecosystems to future
environmental change.
PMID- 28410033
TI - Student nurse mentoring: an evaluative study of the mentor's perspective.
AB - An evaluative study aimed to capture the 'mentor voice' and provide an insight
into the mentoring role from the perspective of the nurse mentor. Participants
from each of the four fields of nursing practice were asked to comment on the
satisfying and frustrating aspects of their mentoring role. The narrative data
gleaned from the evaluation were qualitatively analysed and subsequently
organised into key themes around the student-mentor relationship and the clinical
environment. Given that the landscape of nurse education is set to change, in
terms of new standards from the professional bodies and the political drivers,
not to mention the changing profile of the student nurse, it is hoped that the
findings may help to shape the relationship between the mentor, the student and
the higher education institution.
PMID- 28410035
TI - Easing student stress.
PMID- 28410034
TI - The Barnstaple Leg Club, Devon.
AB - Andrew Kingsley, Sylvie Hampton, Ellie Lindsay and Roland Renyi discuss how the
social model of care has proved its worth in the South West of England.
PMID- 28410036
TI - Using an index of wellbeing to help achieve optimum care for older people.
AB - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
the quest by charity Age UK to better understand the experiences of older people
to help it shape future health and social policy.
PMID- 28410037
TI - Meeting the healthcare needs of adults on the autism spectrum.
AB - People with Asperger's syndrome/high functioning autism (AS/HFA) are just as
likely to experience the full range of health conditions and needs as
'neurotypicals', people who do not have AS/HFA. However, many people with AS/HFA
fall between the cracks of health service design and provision as they do not
receive support from learning disabilities or mental health services. This
article highlights the need for a comprehensive review of healthcare provision,
led by people on the autism spectrum.
PMID- 28410038
TI - Critical care nurses' knowledge and practice of delirium assessment.
AB - AIMS: The aim of this study was to examine perceived barriers to assessment of
delirium for critical care nurses, and the impact of education on their knowledge
and practice. BACKGROUND: Delirium is a significant problem in critical care,
leading to increased morbidity and mortality. Many authors have found variations
in assessment by critical care nurses, but there has been limited analysis of the
reasons for this. Education on the topic improves knowledge and practice, but the
best approach has not been examined. DESIGN: A questionnaire survey design.
METHODS: A self-reported questionnaire was distributed to critical care nurses
(n=31) at a district general hospital. Data were analysed with descriptive
statistics. RESULTS: Knowledge and practice were variable, but correlation was
seen between nursing band and years of experience with better scores. Any type of
education led to significantly improved scores. Several barriers to assessment
were found, with the most common being lack of knowledge and difficulty in
assessing intubated patients. CONCLUSION: It is essential to improve practice in
delirium assessment and management. Education is vital to improve the knowledge
and practice of critical care nurses regarding delirium.
PMID- 28410039
TI - Education does matter: nursing apprenticeships in the workforce.
AB - Elizabeth Rosser, Deputy Dean (Education and Professional Practice) and Professor
of Nursing, Bournemouth University, considers the concerns around seeing
apprenticeships as a solution to the crisis in the workforce.
PMID- 28410040
TI - A vision for the future of nursing.
PMID- 28410041
TI - Implementation and evaluation of a pre-assessment telephone triage system in an
outpatient photopheresis service.
AB - The prompt assessment of patients as fit for photopheresis is imperative to
ensure delivery of a safe and efficient service. Before January 2015 the
photopheresis unit was reliant on patients contacting the department directly to
cancel their appointment if they were unwell or were suffering from any pre
defined exclusion criteria. Methods to reduce the number of cancellations and
patients arriving unwell were therefore examined. The authors combined aspects of
patient pre-assessment with telephone triage to develop a system that could
provide better care and improve the use of resources within the department. The
pre-assessment telephone triage system successfully reduced cancellations and
increased patient awareness of conditions that would prevent delivery of
photopheresis treatment. Subsequently the quality improvement initiative
established that the pre-assessment telephone triage system saved the
photopheresis unit over L33 000 over a 12-month period.
PMID- 28410042
TI - The State of Care report: patient safety in NHS acute hospitals.
AB - John Tingle, Reader in Health Law at Nottingham Trent University, discusses the
Care Quality Commission's recently published report on the quality of hospital
care in England.
PMID- 28410043
TI - Optimising inhaler technique in chronic obstructive pulmonary disease: a complex
issue.
AB - Inhaled therapies play a central role in the management of chronic obstructive
pulmonary disease (COPD); however, studies indicate that many patients do not use
their inhaled medication as directed, resulting in decreased medication delivery
and suboptimal disease control. Key factors that should be considered when
evaluating whether patients are achieving optimal outcomes with inhaled therapies
are: if patients are using a correct inhalation technique; if patients have
adequate dexterity to use the prescribed inhaler; if patients have sufficient
inspiratory flow rate to achieve adequate lung deposition (for dry powder
inhalers); and if the inhaler is accepted by the patient. There are many
different types of dry powder inhalers available for COPD medications and their
specific features can affect ease of use and suitability and acceptability for
individual patients and patients' preferences.
PMID- 28410044
TI - Tackling comorbidity associated with rheumatic diseases in standard practice.
AB - In spite of the dramatic improvement of the long-term prognosis of inflammatory
arthritic conditions, patients living with arthritis remain more likely to have a
shorter lifespan in contrast to the age-matched population without arthritis.
This high incidence of morbidity-mortality has been attributed to an increased
prevalence of comorbidities, particularly cardiovascular disease, infections, and
the development of malignant space-occupying lesions. In spite of the published
guidelines highlighting the importance of comorbidity assessment and management,
implementing these recommendations in standard clinical practice remains a
challenge for the treating rheumatologists and rheumatology nurse specialists.
This article will review the challenge of comorbidity in inflammatory arthritic
conditions and its dynamic nature, the impact on patient management, as well as
recent trends in the screening and assessment of comorbidity risk in standard
clinical practice.
PMID- 28410045
TI - The role of the biologics nurse specialist in rheumatology.
PMID- 28410046
TI - Deprivation of liberty safeguard deaths: changes to reporting requirements.
AB - Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses
changes to the requirement to report deaths of patients subject to a deprivation
of liberty safeguards standard authorisation to the coroner.
PMID- 28410047
TI - Demystifying research: it's for everyone.
AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, explains how
practical guidance is now available to help all nurses-including those starting
their careers on the frontline-to contribute to research.
PMID- 28410048
TI - Lag Synchronization Criteria for Memristor-Based Coupled Neural Networks via
Parameter Mismatches Analysis Approach.
AB - This letter focuses on lag synchronization control analysis for memristor-based
coupled neural networks with parameter mismatches. Due to the parameter
mismatches, lag complete synchronization in general cannot be achieved. First,
based on the [Formula: see text]-measure method, generalized Halanay inequality,
together with control algorithms, some sufficient conditions are obtained to
ensure that coupled memristor-based neural networks are in a state of lag
synchronization with an error. Moreover, the error level is estimated. Second, we
show that memristor-based coupled neural networks with parameter mismatches can
reach lag complete synchronization under a discontinuous controller. Finally, two
examples are given to illustrate the effectiveness of the proposed criteria and
well support theoretical results.
PMID- 28410049
TI - A Customized Attention-Based Long Short-Term Memory Network for Distant
Supervised Relation Extraction.
AB - Distant supervision, a widely applied approach in the field of relation
extraction can automatically generate large amounts of labeled training corpus
with minimal manual effort. However, the labeled training corpus may have many
false-positive data, which would hurt the performance of relation extraction.
Moreover, in traditional feature-based distant supervised approaches, extraction
models adopt human design features with natural language processing. It may also
cause poor performance. To address these two shortcomings, we propose a
customized attention-based long short-term memory network. Our approach adopts
word-level attention to achieve better data representation for relation
extraction without manually designed features to perform distant supervision
instead of fully supervised relation extraction, and it utilizes instance-level
attention to tackle the problem of false-positive data. Experimental results
demonstrate that our proposed approach is effective and achieves better
performance than traditional methods.
PMID- 28410050
TI - The Deterministic Information Bottleneck.
AB - Lossy compression and clustering fundamentally involve a decision about which
features are relevant and which are not. The information bottleneck method (IB)
by Tishby, Pereira, and Bialek ( 1999 ) formalized this notion as an information
theoretic optimization problem and proposed an optimal trade-off between throwing
away as many bits as possible and selectively keeping those that are most
important. In the IB, compression is measured by mutual information. Here, we
introduce an alternative formulation that replaces mutual information with
entropy, which we call the deterministic information bottleneck (DIB) and argue
better captures this notion of compression. As suggested by its name, the
solution to the DIB problem turns out to be a deterministic encoder, or hard
clustering, as opposed to the stochastic encoder, or soft clustering, that is
optimal under the IB. We compare the IB and DIB on synthetic data, showing that
the IB and DIB perform similarly in terms of the IB cost function, but that the
DIB significantly outperforms the IB in terms of the DIB cost function. We also
empirically find that the DIB offers a considerable gain in computational
efficiency over the IB, over a range of convergence parameters. Our derivation of
the DIB also suggests a method for continuously interpolating between the soft
clustering of the IB and the hard clustering of the DIB.
PMID- 28410051
TI - Information Rate Analysis of a Synaptic Release Site Using a Two-State Model of
Short-Term Depression.
AB - Synapses are the communication channels for information transfer between neurons;
these are the points at which pulse-like signals are converted into the
stochastic release of quantized amounts of chemical neurotransmitter. At many
synapses, prior neuronal activity depletes synaptic resources, depressing
subsequent responses of both spontaneous and spike-evoked releases. We
analytically compute the information transmission rate of a synaptic release
site, which we model as a binary asymmetric channel. Short-term depression is
incorporated by assigning the channel a memory of depth one. A successful
release, whether spike evoked or spontaneous, decreases the probability of a
subsequent release; if no release occurs on the following time step, the release
probabilities recover back to their default values. We prove that synaptic
depression can increase the release site's information rate if spontaneous
release is more strongly depressed than spike-evoked release. When depression
affects spontaneous and evoked release equally, the information rate must
invariably decrease, even when the rate is normalized by the resources used for
synaptic transmission. For identical depression levels, we analytically disprove
the hypothesis, at least in this simplified model, that synaptic depression
serves energy- and information-efficient encoding.
PMID- 28410052
TI - Robust Averaging of Covariances for EEG Recordings Classification in Motor
Imagery Brain-Computer Interfaces.
AB - The estimation of covariance matrices is of prime importance to analyze the
distribution of multivariate signals. In motor imagery-based brain-computer
interfaces (MI-BCI), covariance matrices play a central role in the extraction of
features from recorded electroencephalograms (EEGs); therefore, correctly
estimating covariance is crucial for EEG classification. This letter discusses
algorithms to average sample covariance matrices (SCMs) for the selection of the
reference matrix in tangent space mapping (TSM)-based MI-BCI. Tangent space
mapping is a powerful method of feature extraction and strongly depends on the
selection of a reference covariance matrix. In general, the observed signals may
include outliers; therefore, taking the geometric mean of SCMs as the reference
matrix may not be the best choice. In order to deal with the effects of outliers,
robust estimators have to be used. In particular, we discuss and test the use of
geometric medians and trimmed averages (defined on the basis of several metrics)
as robust estimators. The main idea behind trimmed averages is to eliminate data
that exhibit the largest distance from the average covariance calculated on the
basis of all available data. The results of the experiments show that while the
geometric medians show little differences from conventional methods in terms of
classification accuracy in the classification of electroencephalographic
recordings, the trimmed averages show significant improvement for all subjects.
PMID- 28410053
TI - Nested-Clique Network Model of Neural Associative Memory.
AB - Clique-based neural associative memories introduced by Gripon and Berrou (GB),
have been shown to have good performance, and in our previous work we improved
the learning capacity and retrieval rate by local coding and precoding in the
presence of partial erasures. We now take a step forward and consider nested
clique graph structures for the network. The GB model stores patterns as small
cliques, and we here replace these by nested cliques. Simulation results show
that the nested-clique structure enhances the clique-based model.
PMID- 28410054
TI - Chaotic Pattern Alternations Can Reproduce Properties of Dominance Durations in
Multistable Perception.
AB - We propose a pulse neural network that exhibits chaotic pattern alternations
among stored patterns as a model of multistable perception, which is reflected in
phenomena such as binocular rivalry and perceptual ambiguity. When we regard the
mixed state of patterns as a part of each pattern, the durations of the retrieved
pattern obey unimodal distributions. We confirmed that no chaotic properties are
observed in the time series of durations, consistent with the findings of
previous psychological studies. Moreover, it is shown that our model also
reproduces two properties of multistable perception that characterize the
relationship between the contrast of inputs and the durations.
PMID- 28410055
TI - Olfactory Recognition Based on EEG Gamma-Band Activity.
AB - There are various kinds of brain monitoring techniques, including local field
potential, near-infrared spectroscopy, magnetic resonance imaging (MRI), positron
emission tomography, functional MRI, electroencephalography (EEG), and
magnetoencephalography. Among those techniques, EEG is the most widely used one
due to its portability, low setup cost, and noninvasiveness. Apart from other
advantages, EEG signals also help to evaluate the ability of the smelling organ.
In such studies, EEG signals, which are recorded during smelling, are analyzed to
determine the subject lacks any smelling ability or to measure the response of
the brain. The main idea of this study is to show the emotional difference in EEG
signals during perception of valerian, lotus flower, cheese, and rosewater odors
by the EEG gamma wave. The proposed method was applied to the EEG signals, which
were taken from five healthy subjects in the conditions of eyes open and eyes
closed at the Swiss Federal Institute of Technology. In order to represent the
signals, we extracted features from the gamma band of the EEG trials by
continuous wavelet transform with the selection of Morlet as a wavelet function.
Then the [Formula: see text]-nearest neighbor algorithm was implemented as the
classifier for recognizing the EEG trials as valerian, lotus flower, cheese, and
rosewater. We achieved an average classification accuracy rate of 87.50% with the
4.3 standard deviation value for the subjects in eyes-open condition and an
average classification accuracy rate of 94.12% with the 2.9 standard deviation
value for the subjects in eyes-closed condition. The results prove that the
proposed continuous wavelet transform-based feature extraction method has great
potential to classify the EEG signals recorded during smelling of the present
odors. It has been also established that gamma-band activity of the brain is
highly associated with olfaction.
PMID- 28410056
TI - Generalization Analysis of Fredholm Kernel Regularized Classifiers.
AB - Recently, a new framework, Fredholm learning, was proposed for semisupervised
learning problems based on solving a regularized Fredholm integral equation. It
allows a natural way to incorporate unlabeled data into learning algorithms to
improve their prediction performance. Despite rapid progress on implementable
algorithms with theoretical guarantees, the generalization ability of Fredholm
kernel learning has not been studied. In this letter, we focus on investigating
the generalization performance of a family of classification algorithms, referred
to as Fredholm kernel regularized classifiers. We prove that the corresponding
learning rate can achieve [Formula: see text] ([Formula: see text] is the number
of labeled samples) in a limiting case. In addition, a representer theorem is
provided for the proposed regularized scheme, which underlies its applications.
PMID- 28410057
TI - Learning Rates for Classification with Gaussian Kernels.
AB - This letter aims at refined error analysis for binary classification using
support vector machine (SVM) with gaussian kernel and convex loss. Our first
result shows that for some loss functions, such as the truncated quadratic loss
and quadratic loss, SVM with gaussian kernel can reach the almost optimal
learning rate provided the regression function is smooth. Our second result shows
that for a large number of loss functions, under some Tsybakov noise assumption,
if the regression function is infinitely smooth, then SVM with gaussian kernel
can achieve the learning rate of order [Formula: see text], where [Formula: see
text] is the number of samples.
PMID- 28410058
TI - Local Intrinsic Dimension Estimation by Generalized Linear Modeling.
AB - We propose a method for intrinsic dimension estimation. By fitting the power of
distance from an inspection point and the number of samples included inside a
ball with a radius equal to the distance, to a regression model, we estimate the
goodness of fit. Then, by using the maximum likelihood method, we estimate the
local intrinsic dimension around the inspection point. The proposed method is
shown to be comparable to conventional methods in global intrinsic dimension
estimation experiments. Furthermore, we experimentally show that the proposed
method outperforms a conventional local dimension estimation method.
PMID- 28410061
TI - The American Telemedicine Association ATA 2017 Telehealth 2.0 Conference
Abstracts.
PMID- 28410059
TI - Corrigendum.
PMID- 28410062
TI - Role of Imaging in the Evaluation of Male Infertility.
AB - Infertility is defined herein as the inability to achieve pregnancy after
frequently engaging in unprotected sexual intercourse for 1 year. Among infertile
couples, the cause of infertility involves the male partner in approximately 50%
of cases. Male infertility is usually caused by conditions affecting sperm
production, sperm function, or both, or blockages that prevent the delivery of
sperm. Chronic health problems, injuries, lifestyle choices, anatomic problems,
hormonal imbalances, and genetic defects can have a role in male infertility. The
diagnostic workup of male infertility should include a thorough medical and
reproductive history, physical examination, and semen analysis, followed by
imaging. The main role of imaging is identification of the causes of infertility,
such as congenital anomalies and disorders that obstruct sperm transport and may
be correctable. Scrotal ultrasonography is the most common initially performed
noninvasive examination used to image the male reproductive system, including the
testes and extratesticular structures such as the epididymis. Magnetic resonance
(MR) imaging is another noninvasive imaging modality used in the pelvis to
evaluate possible obstructive lesions involving the ductal system. MR imaging of
the brain is extremely useful for evaluating relevant neurologic abnormalities,
such as pituitary gland disorders, that are suspected on the basis of hormone
analysis results. Invasive techniques are usually reserved for therapeutic
interventions in patients with known abnormalities. In this article, the causes
and imaging findings of obstructive and nonobstructive azoospermia are discussed.
In addition to detecting treatable conditions that are related to male
infertility, identifying the life-threatening entities associated with
infertility and the genetic conditions that could be transmitted to offspring
especially in patients who undergo assisted reproduction-is critical. (c)RSNA,
2017.
PMID- 28410063
TI - Troubleshooting to Overcome Technical Challenges in Image-guided Breast Biopsy.
AB - Image-guided breast biopsy with stereotactic, ultrasonographic, or magnetic
resonance imaging guidance has become an integral component of every breast
imaging program. It has many advantages over open surgical biopsy, including
lower cost, lower patient morbidity, faster patient recovery, and minimal to no
scarring, with equal accuracy to that of open surgical biopsy. Successful
completion of a breast biopsy begins with thorough preprocedural planning to
choose the appropriate imaging modality and most efficient biopsy approach.
Patient mental and physical comorbidities, anticoagulation status, small or thin
breasts, and breast implants, as well as lesion conspicuity and posterior,
superficial, axillary, or subareolar location, pose technical challenges to
successful image-guided breast biopsy that must be overcome. When biopsy is
performed with use of a different imaging modality than that used to initially
identify the target, careful preprocedural multimodality radiologic correlation,
postprocedural identification of the biopsy marker location, and radiologic
pathologic correlation must be undertaken to ensure accurate biopsy of the
intended target with use of the different modality. If, after employing all
available strategic and procedural modifications, image-guided breast biopsy
cannot be performed, then surgical excision of the intended target should be
recommended at the time of biopsy cancellation to avoid a delay in diagnosis.
This article reviews patient and lesion factors that pose technical challenges to
successful breast biopsy and presents strategies and procedural modifications
that aid in successful completion of breast biopsy in challenging situations.
(c)RSNA, 2017.
PMID- 28410064
TI - ?
PMID- 28410065
TI - ?
PMID- 28410066
TI - Health Professionals Working With First Nations, Inuit, and Metis Consensus
Guideline.
AB - OBJECTIVE: Our aim is to provide health care professionals in Canada with the
knowledge and tools to provide culturally safe care to First Nations, Inuit, and
Metis women and through them, to their families, in order to improve the health
of First Nations, Inuit, and Metis. EVIDENCE: Published literature was retrieved
through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane
Library in 2011 using appropriate controlled vocabulary (e.g., cultural
competency, health services, indigenous, transcultural nursing) and key words
(e.g, indigenous health services, transcultural health care, cultural safety).
Targeted searches on subtopics (e.g, ceremonial rites and sexual coming of age)
were also performed. The PubMed search was restricted to the years 2005 and later
because of the large number of records retrieved on this topic. Searches were
updated on a regular basis and incorporated in the guideline to May 2012. Grey
(unpublished) literature was identified through searching the websites of
selected related agencies (e.g, Campbell Collaboration, Social Care Online,
Institute for Healthcare Improvement) VALUES: The quality of evidence in this
document was rated using the criteria described in the Report of the Canadian
Task force on Preventive Health Care (Table). SPONSORS: This consensus guideline
was supported by the First Nations and Inuit Health Branch, Health Canada.
PMID- 28410068
TI - The Birth of Gossip.
PMID- 28410067
TI - ?
PMID- 28410070
TI - Chapter 3 Social Determinants of Health Among First Nations, Inuit, and Metis.
PMID- 28410069
TI - Health Professionals Working With First Nations, Inuit, and Metis Consensus
Guideline.
AB - OBJECTIVE: Our aim is to provide health care professionals in Canada with the
knowledge and tools to provide culturally safe care to First Nations, Inuit, and
Metis women and through them, to their families, in order to improve the health
of First Nations, Inuit, and Metis. EVIDENCE: Published literature was retrieved
through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane
Library in 2011 using appropriate controlled vocabulary (e.g., cultural
competency, health services, indigenous, transcultural nursing) and key words
(e.g., indigenous health services, transcultural health care, cultural safety).
Targeted searches on subtopics (e.g., ceremonial rites and sexual coming of age)
were also performed. The PubMed search was restricted to the years 2005 and later
because of the large number of records retrieved on this topic. Searches were
updated on a regular basis and incorporated in the guideline to May 2012. Grey
(unpublished) literature was identified through searching the websites of
selected related agencies (e.g., Campbell Collaboration, Social Care Online,
Institute for Healthcare Improvement). VALUES: The quality of evidence in this
document was rated using the criteria described in the Report of the Canadian
Task force on Preventive Health Care (Table 1). SPONSORS: This consensus
guideline was supported by the First Nations and Inuit Health Branch, Health
Canada.
PMID- 28410071
TI - Chapter 4 Health Systems, Policies, and Services for First Nations, Inuit, and
Metis.
PMID- 28410072
TI - Chapter 5 First Nations, Inuit, and Metis Women's Sexual and Reproductive Health.
PMID- 28410073
TI - Chapter 6 First Nations, Inuit, and Metis Maternal Health.
PMID- 28410074
TI - Chapter 7 Mature Women's Health.
PMID- 28410075
TI - Chapter 8 Changing Outcomes Through Culturally Competent Care.
PMID- 28410076
TI - Chapter 9 Conclusion.
PMID- 28410077
TI - Chapter 10 Case Studies.
PMID- 28410078
TI - Appendix 1. Apology for the Forced Relocation of Inukjuak and Pond Inlet
Families.
PMID- 28410079
TI - Appendix 2. Apology for the Residential School System.
PMID- 28410080
TI - Introduction.
PMID- 28410081
TI - Appendix 3. Avoiding Re-Traumatization of Sexual Abuse/Assault Victims During the
Birthing Process.
PMID- 28410082
TI - Chapter 1 Definitions.
PMID- 28410083
TI - Chapter 2 Demographics.
PMID- 28410084
TI - Clinical and Electroencephalographic Characteristics of Infantile-Onset
Epilepsies Caused by Genetic Mutations.
AB - OBJECTIVES: To determine whether certain characteristic electroencephalography
(EEG) features are indicative of a genetic cause in early-life epilepsy. STUDY
DESIGN: We enrolled a total of 100 patients with infantile-onset (<3 years)
epilepsy due to known genetic cause (n = 50) and nongenetic cause (acquired,
structural, or unknown, n = 50). The genetic group was classified into
synaptopathies, channelopathies, mTOR (mammalian target of rapamycin)-opathies,
and chromosomal abnormalities. The nongenetic group included epilepsy of unknown
cause and structural abnormalities such as brain tumor, focal cortical dysplasia
and encephalomalacia. The clinical features, magnetic resonance imaging, and
video EEG obtained before 3 years of age and again at follow-up were reviewed.
Specifically, the background rhythms and patterns of interictal epileptiform
discharges were analyzed to define the EEG characteristics. RESULTS: The genetic
group was more likely to have seizure recurrence beyond infancy and significant
developmental delay (P <.01). The genetic and nongenetic groups showed different
EEG patterns in the initial EEGs that persisted in follow-up EEGs. Diffuse
slowing with pleomorphic focal/multifocal epileptiform discharges were present
more often in the genetic (86%) compared with the nongenetic group (20%) in the
initial EEGs (P <.01). The last available follow-up EEG features were similar
(81% in genetic versus 17% in nongenetic) to the EEG performed prior to 3 years
of age. CONCLUSIONS: Our findings suggest a simple guide for genetic screening in
children with early-onset epilepsy. Genetic testing may be indicated and useful
in infants with delayed development, no obvious cause, and significant EEG
background slowing with pleomorphic focal or multifocal epileptiform discharges.
PMID- 28410085
TI - Early Solid Food Introduction: Role in Food Allergy Prevention and Implications
for Breastfeeding.
PMID- 28410086
TI - Premature Discontinuation of Pediatric Randomized Controlled Trials: A
Retrospective Cohort Study.
AB - OBJECTIVES: To determine the proportion of pediatric randomized controlled trials
(RCTs) that are prematurely discontinued, examine the reasons for
discontinuation, and compare the risk for recruitment failure in pediatric and
adult RCTs. STUDY DESIGN: A retrospective cohort study of RCTs approved by 1 of 6
Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between
2000 and 2003. We recorded trial characteristics, trial discontinuation, and
reasons for discontinuation from protocols, corresponding publications, REC
files, and a survey of trialists. RESULTS: We included 894 RCTs, of which 86
enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs
and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56%
of pediatric RCT discontinuations and 43% of adult RCT discontinuations.
Multivariable logistic regression analyses suggested that pediatric RCT was not
an independent risk factor for recruitment failure after adjustment for other
potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors
were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship
(aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95%
CI 1.01-1.09, in decrements of 100 participants). CONCLUSION: Forty percent of
pediatric RCTs were discontinued prematurely, owing predominately to slow
recruitment. Enrollment of children was not an independent risk factor for
recruitment failure.
PMID- 28410088
TI - Improvements in treatment of children younger than age 5 years infected with
Ebola virus.
PMID- 28410087
TI - Racial and Ethnic Disparities in Parental Refusal of Consent in a Large,
Multisite Pediatric Critical Care Clinical Trial.
AB - OBJECTIVE: To evaluate whether race or ethnicity was independently associated
with parental refusal of consent for their child's participation in a multisite
pediatric critical care clinical trial. STUDY DESIGN: We performed a secondary
analyses of data from Randomized Evaluation of Sedation Titration for Respiratory
Failure (RESTORE), a 31-center cluster randomized trial of sedation management in
critically ill children with acute respiratory failure supported on mechanical
ventilation. Multivariable logistic regression modeling estimated associations
between patient race and ethnicity and parental refusal of study consent. RESULT:
Among the 3438 children meeting enrollment criteria and approached for consent,
2954 had documented race/ethnicity of non-Hispanic White (White), non-Hispanic
Black (Black), or Hispanic of any race. Inability to approach for consent was
more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic
children (13.2%). Among those offered consent, parents of Black (29.5%) and
Hispanic children (25.9%) more frequently refused consent than parents of White
children (18.2%, P < .0167 for each). Compared with parents of White children,
parents of Black (OR 2.15, 95% CI 1.56-2.95, P < .001) and Hispanic (OR 1.44, 95%
CI 1.10-1.88, P = .01) children were more likely to refuse consent. Parents of
children offered participation in the intervention arm were more likely to refuse
consent than parents in the control arm (OR 2.15, 95% CI 1.37-3.36, P < .001).
CONCLUSIONS: Parents of Black and Hispanic children were less likely to be
approached for, and more frequently declined consent for, their child's
participation in a multisite critical care clinical trial. Ameliorating this
racial disparity may improve the validity and generalizability of study findings.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00814099.
PMID- 28410090
TI - Reply.
PMID- 28410089
TI - Mortality and Morbidity after Laparoscopic Surgery in Children with and without
Congenital Heart Disease.
AB - OBJECTIVES: To determine the risk of morbidity and mortality after laparoscopic
surgery among children with congenital heart disease (CHD). STUDY DESIGN: Cohort
study using the 2013-2014 National Surgical Quality Improvement Program
Pediatrics, which prospectively collected data at 56 and 64 hospitals in 2013 and
2014, respectively. Primary exposure was CHD. Primary outcome was overall in
hospital postoperative mortality. Secondary outcomes included 30-day mortality
and 30-day morbidity (any nondeath adverse event). Among 34?543 children who
underwent laparoscopic surgery, 1349, 1106, and 266 had minor, major, and severe
CHD, respectively. After propensity score matching within each stratum of CHD
severity, morbidity and mortality were compared between children with and without
CHD. RESULTS: Children with severe CHD had higher overall mortality and 30-day
morbidity (OR 12.31, 95% CI 1.59-95.01; OR 2.51, 95% CI 1.57-4.01, respectively),
compared with matched controls. Overall mortality and 30-day morbidity were also
higher among children with major CHD compared with children without CHD (OR 3.46,
95% CI 1.49-8.06; OR 2.07, 95% CI 1.65-2.61, respectively). Children with minor
CHD had similar mortality outcomes, but had higher 30-day morbidity compared with
children without CHD (OR 1.71, 95% CI 1.37-2.13). CONCLUSIONS: Children with
major or severe CHD have higher morbidity and mortality after laparoscopic
surgery. Clinicians should consider the increased risks of laparoscopic surgery
for these children during medical decision making.
PMID- 28410091
TI - Maternal Attitudes and Other Factors Associated with Infant Vaccination Status in
the United States, 2011-2014.
AB - OBJECTIVE: To assess the role of maternal attitudes and other factors associated
with infant vaccination status. STUDY DESIGN: Data on reported vaccination status
were analyzed from a nationally representative prospective survey of mothers of 2
to 6-month-old infants. Weighted univariate and multiple logistic regression
analyses were conducted. Latent profile analysis of mothers reporting
nonimmunized infants identified distinct groups, RESULTS: Of 3268 mothers, 2820
(weighted 86.2%), 311 (9.1%), and 137 (4.7%), respectively, reported their infant
had received all, some, or no recommended vaccinations for age. Younger infants
and infants with younger mothers were more likely to have received no
vaccinations. Mothers with neutral and negative attitudes toward vaccination were
>3 (aOR 3.66, 95% CI 1.80-7.46) and 43 times (aOR 43.23, 95% CI 20.28-92.16),
respectively, more likely than mothers with positive attitudes to report their
infants had received no vaccinations. Two subgroups of mothers reporting that
their infants had received no vaccinations were identified: group A (52.5%) had
less than positive attitudes and less than positive subjective norms about
vaccination (ie, perceived social pressure from others); group B (47.5%) had
positive attitudes and positive subjective norms. Group A mothers were more
likely to be white (76.1% vs 48.3%, P?=?.002), more educated (43.5% vs 35.4%
college or higher, P?=?.02), and to exclusively breastfeed (74.9% vs. 27.3%,
P?8.0 mL/kg, respectively), compared with 29% in the NICU (P < .001,
chi2 test). The use of a flow-inflating bag resulted in a median (range) VT of
8.5 mL/kg (range, 5.3-11.4 mL/kg) vs 5.6 ml/kg (range, 4.3-7.9 mL/kg) using a
Neopuff T-piece system (P < .0001, Mann-Whitney U test). The mean anesthetic
machine expiratory VT was 3.2 mL/kg (95% CI, -4.5 to 10.8 mL/kg) above RFM.
CONCLUSIONS: VT is highly variable during the anesthetic care of neonates, and
potentially injurious VT is frequently delivered; thus, we suggest close VT
monitoring using a dedicated neonatal RFM.
PMID- 28410094
TI - Stiffness Perception During Active Ankle and Knee Movement.
AB - OBJECTIVE: Recently, human joint impedance-the instantaneous mechanical response
to a perturbation-has been quantified during gait, providing new insight beyond
the traditional biomechanical descriptions of kinetics and kinematics. However,
the role of joint impedance in neuromotor control and the development of
exoskeletons and other wearable robotic systems remains unknown. One approach to
studying the role of impedance in neuromotor control involves characterizing the
human ability to discriminate changes in external impedance properties. Thus, the
purpose of this work is to quantify the minimum detectable change in the
stiffness component of impedance when interacting with an external mechanical
impedance at the human ankle or knee. METHODS: A dynamometer coupled to subjects'
right ankle or knee rendered the dynamics of a virtual rotational spring-mass
damper system. The minimum detectable change, or just noticeable difference, was
determined via a weighted up-down staircase method in which subjects compared the
stiffness values of two different controller configurations. RESULTS: We found
that subjects could reliably detect stiffness changes of at least 12% at the
ankle and 13% at the knee. CONCLUSION: Stiffness errors or variations produced by
an external mechanical device will be undetected if they remain below the 12-13%
threshold. SIGNIFICANCE: Our results provide novel insight into how the
sensorimotor system senses joint impedance, information that may improve the
design and control of impedance-based wearable robotic technologies.
PMID- 28410096
TI - Leave-One-Out Kernel Optimization for Shadow Detection and Removal.
AB - The objective of this work is to detect shadows in images. We pose this as the
problem of labeling image regions, where each region corresponds to a group of
superpixels. To predict the label of each region, we train a kernel Least-Squares
Support Vector Machine (LSSVM) for separating shadow and non-shadow regions. The
parameters of the kernel and the classifier are jointly learned to minimize the
leave-one-out cross validation error. Optimizing the leave-one-out cross
validation error is typically difficult, but it can be done efficiently in our
framework. Experiments on two challenging shadow datasets, UCF and UIUC, show
that our region classifier outperforms more complex methods. We further enhance
the performance of the region classifier by embedding it in a Markov Random Field
(MRF) framework and adding pairwise contextual cues. This leads to a method that
outperforms the state-of-the-art for shadow detection. In addition we propose a
new method for shadow removal based on region relighting. For each shadow region
we use a trained classifier to identify a neighboring lit region of the same
material. Given a pair of lit-shadow regions we perform a region relighting
transformation based on histogram matching of luminance values between the shadow
region and the lit region. Once a shadow is detected, we demonstrate that our
shadow removal approach produces results that outperform the state of the art by
evaluating our method using a publicly available benchmark dataset.
PMID- 28410095
TI - Position and Orientation Insensitive Wireless Power Transmission for EnerCage
Homecage System.
AB - We have developed a new headstage architecture as part of a smart experimental
arena, known as the EnerCage-HC2 system, which automatically delivers stimulation
and collects behavioral data over extended periods with minimal small animal
subject handling or personnel intervention in a standard rodent homecage.
Equipped with a four-coil inductive link, the EnerCage-HC2 system wirelessly
powers the receiver (Rx) headstage, irrespective of the subject's location or
head orientation, eliminating the need for tethering or carrying bulky batteries.
On the transmitter (Tx) side, a driver coil, five high-quality (Q) factor
segmented resonators at different heights and orientations, and a closed-loop Tx
power controller create a homogeneous electromagnetic (EM) field within the
homecage 3-D space, and compensate for drops in power transfer efficiency (PTE)
due to Rx misalignments. The headstage is equipped with four small slanted
resonators, each covering a range of head orientations with respect to the Tx
resonators, which direct the EM field toward the load coil at the bottom of the
headstage. Moreover, data links based on Wi-Fi, UART, and Bluetooth low energy
are utilized to enables remote communication and control of the Rx. The PTE
varies within 23.6%-33.3% and 6.7%-10.1% at headstage heights of 8 and 20 cm,
respectively, while continuously delivering >40 mW to the Rx electronics even at
90 degrees rotation. As a proof of EnerCage-HC2 functionality in vivo, a
previously documented on-demand electrical stimulation of the globus pallidus,
eliciting consistent head rotation, is demonstrated in three freely behaving
rats.
PMID- 28410097
TI - Progressive Minimal Path Method for Segmentation of 2D and 3D Line Structures.
AB - We propose a novel minimal path method for the segmentation of 2D and 3D line
structures. Minimal path methods perform propagation of a wavefront emanating
from a start point at a speed derived from image features, followed by path
extraction using backtracing. Usually, the computation of the speed and the
propagation of the wave are two separate steps, and point features are used to
compute a static speed. We introduce a new continuous minimal path method which
steers the wave propagation progressively using dynamic speed based on path
features. We present three instances of our method, using an appearance feature
of the path, a geometric feature based on the curvature of the path, and a joint
appearance and geometric feature based on the tangent of the wavefront. These
features have not been used in previous continuous minimal path methods. We
compute the features dynamically during the wave propagation, and also
efficiently using a fast numerical scheme and a low-dimensional parameter space.
Our method does not suffer from discretization or metrication errors. We
performed qualitative and quantitative evaluations using 2D and 3D images from
different application areas.
PMID- 28410093
TI - Race, Income, and Disease Outcomes in Juvenile Dermatomyositis.
AB - OBJECTIVE: To determine the relationships among race, income, and disease
outcomes in children with juvenile dermatomyositis (JDM). STUDY DESIGN: Data from
438 subjects with JDM enrolled in the Childhood Arthritis and Rheumatology
Research Alliance (CARRA) Legacy Registry were analyzed. Demographic data
included age, sex, race, annual family income, and insurance status. Clinical
outcomes included muscle strength, presence of rash, calcinosis, weakness,
physical function, and quality of life measures. Disease outcomes were compared
based on race and income. RESULTS: Minority subjects were significantly more
likely to have low annual family income and significantly worse scores on
measures of physical function, disease activity, and quality of life measures.
Subjects with lower annual family income had worse scores on measures of physical
function, disease activity, and quality of life scores, as well as weakness.
Black subjects were more likely to have calcinosis. Despite these differences in
outcome measures, there were no significant differences among the racial groups
in time to diagnosis or duration of disease. Using calcinosis as a marker of
disease morbidity, black race, annual family income <$50 000 per year, negative
antinuclear antibody, and delay in diagnosis >12 months were associated with
calcinosis. CONCLUSION: Minority race and lower family income are associated with
worse morbidity and outcomes in subjects with JDM. Calcinosis was more common in
black subjects. Further studies are needed to examine these associations in more
detail, to support efforts to address health disparities in subjects with JDM and
improve disease outcomes.
PMID- 28410098
TI - Learning a Deep Model for Human Action Recognition from Novel Viewpoints.
AB - Recognizing human actions from unknown and unseen (novel) views is a challenging
problem. We propose a Robust Non-Linear Knowledge Transfer Model (R-NKTM) for
human action recognition from novel views. The proposed R-NKTM is a deep fully
connected neural network that transfers knowledge of human actions from any
unknown view to a shared high-level virtual view by finding a set of non-linear
transformations that connects the views. The R-NKTM is learned from 2D
projections of dense trajectories of synthetic 3D human models fitted to real
motion capture data and generalizes to real videos of human actions. The strength
of our technique is that we learn a single R-NKTM for all actions and all
viewpoints for knowledge transfer of any real human action video without the need
for re-training or fine-tuning the model. Thus, R-NKTM can efficiently scale to
incorporate new action classes. R-NKTM is learned with dummy labels and does not
require knowledge of the camera viewpoint at any stage. Experiments on three
benchmark cross-view human action datasets show that our method outperforms
existing state-of-the-art.
PMID- 28410099
TI - Confidence-Based Data Association and Discriminative Deep Appearance Learning for
Robust Online Multi-Object Tracking.
AB - Online multi-object tracking aims at estimating the tracks of multiple objects
instantly with each incoming frame and the information provided up to the moment.
It still remains a difficult problem in complex scenes, because of the large
ambiguity in associating multiple objects in consecutive frames and the low
discriminability between objects appearances. In this paper, we propose a robust
online multi-object tracking method that can handle these difficulties
effectively. We first define the tracklet confidence using the detectability and
continuity of a tracklet, and decompose a multi-object tracking problem into
small subproblems based on the tracklet confidence. We then solve the online
multi-object tracking problem by associating tracklets and detections in
different ways according to their confidence values. Based on this strategy,
tracklets sequentially grow with online-provided detections, and fragmented
tracklets are linked up with others without any iterative and expensive
association steps. For more reliable association between tracklets and
detections, we also propose a deep appearance learning method to learn a
discriminative appearance model from large training datasets, since the
conventional appearance learning methods do not provide rich representation that
can distinguish multiple objects with large appearance variations. In addition,
we combine online transfer learning for improving appearance discriminability by
adapting the pre-trained deep model during online tracking. Experiments with
challenging public datasets show distinct performance improvement over other
state-of-the-arts batch and online tracking methods, and prove the effect and
usefulness of the proposed methods for online multi-object tracking.
PMID- 28410100
TI - Estimation of Strain Elastography from Ultrasound Radio-Frequency Data by
Utilizing Analytic Gradient of the Similarity Metric.
AB - Most strain imaging techniques follow a pipeline strategy: in the first step,
tissue displacement is estimated from radio-frequency (RF) frames, and in the
second step, a spatial derivative operation is applied. There are two main issues
that arise from this framework. First, the gradient operation amplifies noise,
and therefore, smoothing techniques have to be adopted. Second, strain estimation
does not exploit the original RF data. It rather relies solely on the noisy
displacement field. In this paper, a novel technique is proposed that utilizes
both the displacement field and the RF frames to accurately obtain the strain
estimates. The normalized cross correlation (NCC) metric between two
corresponding windows around the samples of the pre- and post-compressed images
is employed to generate a dissimilarity measurement. The derivative of NCC with
respect to the strain is analytically derived using the chain rule. This allows
an efficient minimization of the dissimilarity metric with respect to the strain
using the gradient descent optimization technique. The effectiveness of the
proposed method is investigated through simulation data, phantom experiments, and
in vivo patient data. The experimental results show that exploiting the
information in RF data significantly improves the strain estimates.
PMID- 28410101
TI - Medical Instrument Detection in 3-Dimensional Ultrasound Data Volumes.
AB - Ultrasound-guided medical interventions are broadly applied in diagnostics and
therapy, e.g., regional anesthesia or ablation. A guided intervention using 2-D
ultrasound is challenging due to the poor instrument visibility, limited field of
view, and the multi-fold coordination of the medical instrument and ultrasound
plane. Recent 3-D ultrasound transducers can improve the quality of the image
guided intervention if an automated detection of the needle is used. In this
paper, we present a novel method for detecting medical instruments in 3-D
ultrasound data that is solely based on image processing techniques and validated
on various ex vivo and in vivo data sets. In the proposed procedure, the
physician is placing the 3-D transducer at the desired position, and the image
processing will automatically detect the best instrument view, so that the
physician can entirely focus on the intervention. Our method is based on the
classification of instrument voxels using volumetric structure directions and
robust approximation of the primary tool axis. A novel normalization method is
proposed for the shape and intensity consistency of instruments to improve the
detection. Moreover, a novel 3-D Gabor wavelet transformation is introduced and
optimally designed for revealing the instrument voxels in the volume, while
remaining generic to several medical instruments and transducer types.
Experiments on diverse data sets, including in vivo data from patients, show that
for a given transducer and an instrument type, high detection accuracies are
achieved with position errors smaller than the instrument diameter in the 0.5-1.5
mm range on average.
PMID- 28410104
TI - Low-Rank Embedding for Robust Image Feature Extraction.
AB - Robustness to noises, outliers, and corruptions is an important issue in linear
dimensionality reduction. Since the sample-specific corruptions and outliers
exist, the class-special structure or the local geometric structure is destroyed,
and thus, many existing methods, including the popular manifold learning- based
linear dimensionality methods, fail to achieve good performance in recognition
tasks. In this paper, we focus on the unsupervised robust linear dimensionality
reduction on corrupted data by introducing the robust low-rank representation
(LRR). Thus, a robust linear dimensionality reduction technique termed low-rank
embedding (LRE) is proposed in this paper, which provides a robust image
representation to uncover the potential relationship among the images to reduce
the negative influence from the occlusion and corruption so as to enhance the
algorithm's robustness in image feature extraction. LRE searches the optimal LRR
and optimal subspace simultaneously. The model of LRE can be solved by
alternatively iterating the argument Lagrangian multiplier method and the
eigendecomposition. The theoretical analysis, including convergence analysis and
computational complexity, of the algorithms is presented. Experiments on some
well-known databases with different corruptions show that LRE is superior to the
previous methods of feature extraction, and therefore, it indicates the
robustness of the proposed method. The code of this paper can be downloaded from
http://www.scholat.com/laizhihui.
PMID- 28410103
TI - The Ultrasound Needle Pulse.
AB - Recent theoretical developments have defined the conditions for forming a
broadband beam that is narrow in axial extent but extended in range. The
formulation is based on the classical angular spectrum decomposition and the
requirement for arranging all spatial and temporal frequencies such that all
components have constant phase propagation between planes. Analytic formulations
are given for a 1-D source and a 2-D axisymmetric source, and comparisons are
made against conventional focused Gaussian beams under similar conditions
relevant to medical imaging systems.
PMID- 28410102
TI - Scanned 3-D Intracardiac ARFI and SWEI for Imaging Radio-Frequency Ablation
Lesions.
AB - Radio-frequency ablation (RFA) is used to locally disrupt electrical propagation
in myocardium and treat arrhythmias, and direct visualization of ablation lesions
by acoustic radiation force methods may benefit RFA procedures. This paper
compares four imaging modalities, B-mode, acoustic radiation force impulse
(ARFI), single-track-location shear wave elasticity imaging (STL-SWEI), and
multiple-track-location shear wave elasticity imaging (MTL-SWEI), in their
ability to resolve RFA lesions in four ex vivo experiments. Ablation lesions are
shown to be marked by at least a local halving of ARFI displacements and doubling
of shear wave speeds. In a controlled ablation of ex vivo porcine and canine
cardiac tissue, STL-SWEI and ARFI are shown to have a similar CNR, better than
MTL-SWEI and B-mode. The SWEI modalities are demonstrated to have improved
imaging of distal lesion boundaries. Gaps smaller than 5 mm are visualized in
ablation lines made of discretely spaced ablations, and complex structures are
reconstructed through depth in an "x" ablation experiment. Scans of suspended
atria show increased noise, but successfully visualize ablations in ARFI, MTL
SWEI, and STL-SWEI.
PMID- 28410105
TI - Dynamical Textures Modeling via Joint Video Dictionary Learning.
AB - Video representation is an important and challenging task in the computer vision
community. In this paper, we consider the problem of modeling and classifying
video sequences of dynamic scenes which could be modeled in a dynamic textures
(DTs) framework. At first, we assume that image frames of a moving scene can be
modeled as a Markov random process. We propose a sparse coding framework, named
joint video dictionary learning (JVDL), to model a video adaptively. By treating
the sparse coefficients of image frames over a learned dictionary as the
underlying "states", we learn an efficient and robust linear transition matrix
between two adjacent frames of sparse events in time series. Hence, a dynamic
scene sequence is represented by an appropriate transition matrix associated with
a dictionary. In order to ensure the stability of JVDL, we impose several
constraints on such transition matrix and dictionary. The developed framework is
able to capture the dynamics of a moving scene by exploring both the sparse
properties and the temporal correlations of consecutive video frames. Moreover,
such learned JVDL parameters can be used for various DT applications, such as DT
synthesis and recognition. Experimental results demonstrate the strong
competitiveness of the proposed JVDL approach in comparison with the state-of-the
art video representation methods. Especially, it performs significantly better in
dealing with DT synthesis and recognition on heavily corrupted data.
PMID- 28410106
TI - Structured Sparse Subspace Clustering: A Joint Affinity Learning and Subspace
Clustering Framework.
AB - Subspace clustering refers to the problem of segmenting data drawn from a union
of subspaces. State-of-the-art approaches for solving this problem follow a two
stage approach. In the first step, an affinity matrix is learned from the data
using sparse or low-rank minimization techniques. In the second step, the
segmentation is found by applying spectral clustering to this affinity. While
this approach has led to the state-of-the-art results in many applications, it is
suboptimal, because it does not exploit the fact that the affinity and the
segmentation depend on each other. In this paper, we propose a joint optimization
framework - Structured Sparse Subspace Clustering (S3C) - for learning both the
affinity and the segmentation. The proposed S3C framework is based on expressing
each data point as a structured sparse linear combination of all other data
points, where the structure is induced by a norm that depends on the unknown
segmentation. Moreover, we extend the proposed S3C framework into Constrained S3C
(CS3C) in which available partial side-information is incorporated into the stage
of learning the affinity. We show that both the structured sparse representation
and the segmentation can be found via a combination of an alternating direction
method of multipliers with spectral clustering. Experiments on a synthetic data
set, the Extended Yale B face data set, the Hopkins 155 motion segmentation
database, and three cancer data sets demonstrate the effectiveness of our
approach.
PMID- 28410107
TI - Feature Sensitive Label Fusion With Random Walker for Atlas-Based Image
Segmentation.
AB - In this paper, a novel label fusion method is proposed for brain magnetic
resonance image segmentation. This label fusion method is formulated on a graph,
which embraces both label priors from atlases and anatomical priors from target
image. To represent a pixel in a comprehensive way, three kinds of feature
vectors are generated, including intensity, gradient, and structural signature.
To select candidate atlas nodes for fusion, rather than exact searching,
randomized k-d tree with spatial constraint is introduced as an efficient
approximation for high-dimensional feature matching. Feature sensitive label
prior (FSLP), which takes both the consistency and variety of different features
into consideration, is proposed to gather atlas priors. As FSLP is a non-convex
problem, one heuristic approach is further designed to solve it efficiently.
Moreover, based on the anatomical knowledge, parts of the target pixels are also
employed as the graph seeds to assist the label fusion process, and an iterative
strategy is utilized to gradually update the label map. The comprehensive
experiments carried out on two publicly available databases give results to
demonstrate that the proposed method can obtain better segmentation quality.
PMID- 28410108
TI - Clearing the Skies: A Deep Network Architecture for Single-Image Rain Removal.
AB - We introduce a deep network architecture called DerainNet for removing rain
streaks from an image. Based on the deep convolutional neural network (CNN), we
directly learn the mapping relationship between rainy and clean image detail
layers from data. Because we do not possess the ground truth corresponding to
real-world rainy images, we synthesize images with rain for training. In contrast
to other common strategies that increase depth or breadth of the network, we use
image processing domain knowledge to modify the objective function and improve
deraining with a modestly sized CNN. Specifically, we train our DerainNet on the
detail (high-pass) layer rather than in the image domain. Though DerainNet is
trained on synthetic data, we find that the learned network translates very
effectively to real-world images for testing. Moreover, we augment the CNN
framework with image enhancement to improve the visual results. Compared with the
state-of-the-art single image de-raining methods, our method has improved rain
removal and much faster computation time after network training.
PMID- 28410109
TI - Classification via Sparse Representation of Steerable Wavelet Frames on Grassmann
Manifold: Application to Target Recognition in SAR Image.
AB - Automatic target recognition has been widely studied over the years, yet it is
still an open problem. The main obstacle consists in extended operating
conditions, e.g.., depression angle change, configuration variation,
articulation, and occlusion. To deal with them, this paper proposes a new
classification strategy. We develop a new representation model via the steerable
wavelet frames. The proposed representation model is entirely viewed as an
element on Grassmann manifolds. To achieve target classification, we embed
Grassmann manifolds into an implicit reproducing Kernel Hilbert space (RKHS),
where the kernel sparse learning can be applied. Specifically, the mappings of
training sample in RKHS are concatenated to form an overcomplete dictionary. It
is then used to encode the counterpart of query as a linear combination of its
atoms. By designed Grassmann kernel function, it is capable to obtain the sparse
representation, from which the inference can be reached. The novelty of this
paper comes from: 1) the development of representation model by the set of
directional components of Riesz transform; 2) the quantitative measure of
similarity for proposed representation model by Grassmann metric; and 3) the
generation of global kernel function by Grassmann kernel. Extensive comparative
studies are performed to demonstrate the advantage of proposed strategy.
PMID- 28410110
TI - Portable and Reconfigurable Wrist Robot Improves Hand Function for Post-Stroke
Subjects.
AB - Rehabilitation robots have become increasingly popular for stroke rehabilitation.
However, the high cost of robots hampers their implementation on a large scale.
This paper implements the concept of a modular and reconfigurable robot, reducing
its cost and size by adopting different therapeutic end effectors for different
training movements using a single robot. The challenge is to increase the robot's
portability and identify appropriate kinds of modular tools and configurations.
Because literature on the effectiveness of this kind of rehabilitation robot is
still scarce, this paper presents the design of a portable and reconfigurable
rehabilitation robot and describes its use with a group of post-stroke patients
for wrist and forearm training. Seven stroke subjects received training using a
reconfigurable robot for 30 sessions, lasting 30 min per session. Post-training,
statistical analysis showed significant improvement of 3.29 points (16.20%, p =
0.027) on the Fugl-Meyer assessment scale for forearm and wrist components.
Significant improvement of active range of motion was detected in both pronation
supination (75.59%, p = 0.018) and wrist flexion-extension (56.12%, p = 0.018)
after the training. These preliminary results demonstrate that the developed
reconfigurable robot could improve subjects' wrist and forearm movement.
PMID- 28410111
TI - A Compact Synchronous Cellular Model of Nonlinear Calcium Dynamics: Simulation
and FPGA Synthesis Results.
AB - Recent studies have demonstrated that calcium is a widespread intracellular ion
that controls a wide range of temporal dynamics in the mammalian body. The
simulation and validation of such studies using experimental data would benefit
from a fast large scale simulation and modelling tool. This paper presents a
compact and fully reconfigurable cellular calcium model capable of mimicking Hopf
bifurcation phenomenon and various nonlinear responses of the biological calcium
dynamics. The proposed cellular model is synthesized on a digital platform for a
single unit and a network model. Hardware synthesis, physical implementation on
FPGA, and theoretical analysis confirm that the proposed cellular model can mimic
the biological calcium behaviors with considerably low hardware overhead. The
approach has the potential to speed up large-scale simulations of slow
intracellular dynamics by sharing more cellular units in real-time. To this end,
various networks constructed by pipelining 10 k to 40 k cellular calcium units
are compared with an equivalent simulation run on a standard PC workstation.
Results show that the cellular hardware model is, on average, 83 times faster
than the CPU version.
PMID- 28410112
TI - Epithelium-Stroma Classification via Convolutional Neural Networks and
Unsupervised Domain Adaptation in Histopathological Images.
AB - Epithelium-stroma classification is a necessary preprocessing step in
histopathological image analysis. Current deep learning based recognition methods
for histology data require collection of large volumes of labeled data in order
to train a new neural network when there are changes to the image acquisition
procedure. However, it is extremely expensive for pathologists to manually label
sufficient volumes of data for each pathology study in a professional manner,
which results in limitations in real-world applications. A very simple but
effective deep learning method, that introduces the concept of unsupervised
domain adaptation to a simple convolutional neural network (CNN), has been
proposed in this paper. Inspired by transfer learning, our paper assumes that the
training data and testing data follow different distributions, and there is an
adaptation operation to more accurately estimate the kernels in CNN in feature
extraction, in order to enhance performance by transferring knowledge from
labeled data in source domain to unlabeled data in target domain. The model has
been evaluated using three independent public epithelium-stroma datasets by cross
dataset validations. The experimental results demonstrate that for epithelium
stroma classification, the proposed framework outperforms the state-of-the-art
deep neural network model, and it also achieves better performance than other
existing deep domain adaptation methods. The proposed model can be considered to
be a better option for real-world applications in histopathological image
analysis, since there is no longer a requirement for large-scale labeled data in
each specified domain.
PMID- 28410113
TI - Watch-Dog: Detecting Self-Harming Activities From Wrist Worn Accelerometers.
AB - In a 2012 survey, in the United States alone, there were more than 35 000
reported suicides with approximately 1800 of being psychiatric inpatients. Recent
Centers for Disease Control and Prevention (CDC) reports indicate an upward trend
in these numbers. In psychiatric facilities, staff perform intermittent or
continuous observation of patients manually in order to prevent such tragedies,
but studies show that they are insufficient, and also consume staff time and
resources. In this paper, we present the Watch-Dog system, to address the problem
of detecting self-harming activities when attempted by in-patients in clinical
settings. Watch-Dog comprises of three key components-Data sensed by tiny
accelerometer sensors worn on wrists of subjects; an efficient algorithm to
classify whether a user is active versus dormant (i.e., performing a physical
activity versus not performing any activity); and a novel decision selection
algorithm based on random forests and continuity indices for fine grained
activity classification. With data acquired from 11 subjects performing a series
of activities (both self-harming and otherwise), Watch-Dog achieves a
classification accuracy of , , and for same-user 10-fold cross-validation, cross
user 10-fold cross-validation, and cross-user leave-one-out evaluation,
respectively. We believe that the problem addressed in this paper is practical,
important, and timely. We also believe that our proposed system is practically
deployable, and related discussions are provided in this paper.
PMID- 28410114
TI - Multilayer Optimization of Heterogeneous Networks Using Grammatical Genetic
Programming.
AB - Heterogeneous cellular networks are composed of macro cells (MCs) and small cells
(SCs) in which all cells occupy the same bandwidth. Provision has been made under
the third generation partnership project-long term evolution framework for
enhanced intercell interference coordination (eICIC) between cell tiers.
Expanding on previous works, this paper instruments grammatical genetic
programming to evolve control heuristics for heterogeneous networks. Three
aspects of the eICIC framework are addressed including setting SC powers and
selection biases, MC duty cycles, and scheduling of user equipments (UEs) at SCs.
The evolved heuristics yield minimum downlink rates three times higher than a
baseline method, and twice that of a state-of-the-art benchmark. Furthermore, a
greater number of UEs receive transmissions under the proposed scheme than in
either the baseline or benchmark cases.
PMID- 28410115
TI - Networked Predictive Control for Nonlinear Systems With Arbitrary Region
Quantizers.
AB - In this paper, networked predictive control is investigated for planar nonlinear
systems with quantization by an extended state observer (ESO). The ESO is used
not only to deal with nonlinear terms but also to generate predictive states for
dealing with network-induced delays. Two arbitrary region quantizers are applied
to take effective values of signals in forward channel and feedback channel,
respectively. Based on a "zoom" strategy, sufficient conditions are given to
guarantee stabilization of the closed-loop networked control system with
quantization. A simulation example is proposed to exhibit advantages and
availability of the results.
PMID- 28410116
TI - Hyperbaric oxygenation for resuscitation and therapy of elderly patients with
cerebral and cardio-respiratory dysfunction.
AB - Hyperbaric oxygenation therapy (HBOT) has been gaining an increasing recognition
as a versatile therapeutic approach. This article reviews the application of
hyperbaric oxygenation as a method for resuscitation and therapy of elderly
patients with cerebral and cardio-respiratory dysfunction, in acute as compared
to chronic impairments. The vital role of proper dosage of HBO therapy to ensure
both the efficacy and safety of the treatment is emphasized. We argue that in the
acute stages of brain and cardiorespiratory impairment, the adequate hyperbaric
oxygen dose is the most important condition for obtaining maximum therapeutic
effect, due to the powerful anti-hypoxic capabilities of this method. In
contrast, during the chronic course of such impairments, there is an increased
importance of safe dosing for the prevention of oxygen intoxication. Further
dosage adjustments need to be made for the elderly as compared to younger
patients, while examining and taking into consideration long term therapy
effects. Some potential geroprotective mechanisms of HBO therapy are considered,
that may be analogous to other geroprotective medications.
PMID- 28410117
TI - Racial disparities: disruptive genes in prostate carcinogenesis.
AB - Population specific studies in prostate cancer (PCa) reveal a unique
heterogeneous etiology. Various factors, such as genetics, environment and
dietary regimen seems to determine disease progression, therapeutic resistance
and rate of mortality. Enormous disparity documented in disease incidences,
aggressiveness and mortality in PCa among AAs (African Americans) and CAs
(Caucasian Americans) is attributed to the variations in genetics, epigenetics
and their association with metabolism. Scientific and clinical evidences have
revealed the influence of variations in Androgen Receptor (AR), RNAse L,
macrophage scavenger receptor 1 (MRS1), androgen metabolism by cytochrome P450
3A4, differential regulation of microRNAs, epigenetic alterations and diet in
racial disparity in PCa incidences and mortality. Concerted efforts are needed to
identify race specific prognostic markers and treatment regimen for a better
management of the disease.
PMID- 28410119
TI - Second law efficiency for living cells.
AB - The exergetic analysis of the biosystems is developed. It takes into account that
cells are able to convert only part of the energy absorbed. The result is to
highlight the fundamental role of the exergy as a quantity useful to develop
considerations on the cells behavior in relation to normal or disease states.
PMID- 28410118
TI - Disparity in rates of HPV infection and cervical cancer in underserved US
populations.
AB - There is a higher rate of HPV infection and cervical cancer incidence and
mortality in underserved US population who reside in Appalachian mountain region
compared to Northern Plains. Social and behavioral factors such as smoking and
alcohol consumption are for such a high incidence. However, by and large, the
reasons for these discrepancies lie in the reluctance of the underserved
population to adopt preventive measures such as prophylactic Human papilloma
virus (HPV) vaccines and Pap smear screening that have significantly reduced the
incidence and mortality rate of cervical cancer in Caucasian women. Thus, it is
clear that drastic change in social behavior and implementation of preventive
measures is required to effectively reduce the incidence and mortality from
cervical cancer in this underserved population.
PMID- 28410120
TI - SNP_TATA_Comparator: genomewide landmarks for preventive personalized medicine.
AB - Year after year, conditions, quality, and duration of human lives have been
improving due to the progress of science, technology, education, and medicine,
which however has a downside. Owing to improvement in children's nutrition,
developmental acceleration occurs that imbalances a child's system. Because of
virtual worlds of the Internet, social experience of teenagers expands and
clashes with puberty of adolescents. Due to the comfort of cities, urbanization
emerges and causes stress to adults because of artificial light, noise,
pollution, violations of personal space, and family disruption. At old age, all
these factors taken together contribute to loneliness, cancer, diabetes, drug
addiction, and sporadic Alzheimer's disease, which shorten the lifespan, as
reviewed in the US, 1990-2010. That is why, a person may ask oneself: "What can I
do now to keep my health in my old age?" To help them, we provide this
comprehensive review on predictive preventive personalized medicine. This branch
of molecular medicine uses single nucleotide polymorphisms to prevent diseases on
the basis of the difference between the individual and reference human genomes.
PMID- 28410121
TI - Nitric oxide signaling during meiotic cell cycle regulation in mammalian oocytes.
AB - Nitric oxide (NO) acts as a major signal molecules and modulate physiology of
mammalian oocytes. Ovarian follicles generate large amount of NO through nitric
oxide synthase (NOS) pathway to maintain diplotene arrest in preovulatory
oocytes. Removal of oocytes from follicular microenvironment or follicular
rupture during ovulation disrupt the flow of NO from granulosa cells to the
oocyte that results a transient decrease of oocyte cytoplasmic NO level.
Decreased NO level reduces cyclic nucleotides level by inactivating guanylyl
cyclases directly or indirectly. The reduced cyclic nucleotides level modulate
specific phosphorylation status of cyclin-dependent kinase 1 (Cdk1) and triggers
cyclin B1 degradation. These changes result in maturation promoting factor (MPF)
destabilization that finally triggers meiotic resumption from diplotene as well
as metaphase-II (M-II) arrest in most of the mammalian species.
PMID- 28410122
TI - High-value compounds from microalgae with industrial exploitability - A review.
AB - From the past several years, algal biotechnology has gained noticeable
interests among research-based organizations and industrial sectors. Recent
studies have provided considerable evidence that microalgae-derived bioactive
compounds could play a vital role in bio- and non-bio sectors of the modern
world. Microalgae-based industrial exploitability ranges from basic biomass-based
food and feeds nutraceuticals to high-value pharmaceuticals, cosmeceuticals,
ecological and biomedical applications. With ever increasing scientific
knowledge, social and environmental awareness, bio-inspired synthesis of
microalgae-based green products, and recent advancements in algal biotechnology
will extend the utilization of microalgae into new areas. Microalgae offer high
biodiversity with an enormous potential to produce structurally complex yet
bioactive compounds which are either impossible or difficult to produce via
synthetic routes. In this paper, a range of value-added bioactive compounds from
microalgae with industrial potentialities has been reviewed. The contribution
ended with a critical description of the main research gaps and envisioned with
future considerations to progress further in this exciting era of research.
PMID- 28410123
TI - Poly(ADP-Ribose) polymerase 1: a therapeutic hope in gynecologic cancers.
AB - The Poly(ADP-ribose) polymerase-1 (PARP1) is a multifunctional nuclear protein
involved in a variety of cellular functions. Recently, its role in the onset,
progression and therapy resistance of cancers in general and reproductive cancers
in particular has been recognised. The PARP associated signaling is perceived to
play a key role in the development, sustenance and relapse of reproductive
cancers. This has led to the preclinical and clinical assessment of PARP
inhibitors as targeted therapeutic agents in reproductive cancers. In the first
part of this review, we have summarized the current status of PARP in the onset,
progression and therapy resistance of reproductive cancers. In the second part of
the review, we have discussed the translational applications of PARP inhibitors,
underscoring the perceived therapeutic opportunities, bottlenecks and the utility
of the ongoing clinical trials.
PMID- 28410124
TI - Wildlife population management: are contraceptive vaccines a feasible
proposition?
AB - To minimize human-animal conflicts for habitation and burden of zoonotic
diseases, it is imperative to develop new strategies for wildlife population
management. In this direction, contraceptive vaccines eliciting immune response
against hormones/proteins critical for reproduction have emerged as one of the
promising options. Contraceptive vaccines based on neutralization of gonadotropin
releasing hormone (GnRH) have been used for inhibition of fertility in various
species such as wild horses, white-tailed deer, pigs, cats, dogs etc. It has been
used for immunocastration of male pigs to improve meat quality. However,
additional safety studies of GnRH vaccine will be needed in light of presence of
its receptor at extra-pituitary sites. Native porcine zona pellucida (PZP)-based
contraceptive vaccines have shown their utility in the management of the
population of both captive and free-ranging wild horses and white-tailed deer.
Long-term use of the PZP-based contraceptive vaccines has also demonstrated their
safety. Ideally single injection of the contraceptive vaccine should elicit long
lasting immune response and desired contraceptive efficacy, which will require
development of novel vaccine delivery platforms and more potent adjuvants.
PMID- 28410125
TI - Multi-omics and male infertility: status, integration and future prospects.
AB - Within the cell, gene expression analysis is the key to gain information about
different cellular and physiological events. The multifaceted route of
fertilization is a combination of different processes, which include production,
maturation and ejaculation of the sperm, its travel through the female genital
tract, followed by the ultimate fusion of the fertile sperm with the egg. Early
embryogenesis and gametogenesis as well as gene expression at tissue level and
global gene silencing are under different levels of stringent epigenetic checks.
Moreover, transcriptome (expressed segment of the genome in form of RNA) and the
proteome (expressed set of genomic proteins) contribute uniformly to the overall
cellular gene expression. In both normal and pathophysiological environments,
this gene expression is altered across various levels viz., genome variations,
post-transcriptional modifications, protein expression and post translational
modifications. Consequently, more informative conclusions can be drawn through a
new 'omics' approach of system biology, which takes into account all the
genomics, epigenomics, proteomics, and metabolomics findings under one roof, thus
computing the alterations in all the entities (genes, proteins, metabolites)
concurrently.
PMID- 28410126
TI - Fertilization failure and gamete health: Is there a link?
AB - Fertilization is a hallmark event of sexual reproduction marked by the fusion of
male and female gamete to form zygote. It is a highly complex, yet a robust
process that is intricately regulated by various signalling molecules. A healthy
fertilization is determined by the quality of zygote which is contingent on the
health of egg and sperm. The relationship between infertility and gametic health
can be reciprocal. On one hand gametogenesis has to be dynamic and unremitting to
sustain the reproductive health, while on the other hand it has to be error free
for proper embryonic development. Complex cellular interactions make
gametogenesis highly vulnerable to extrinsic as well as intrinsic intrusions.
Molecular disparities during these phases may result in complete fertilization
failure. Present review provides an overview of the regulation of gametogenesis,
determinants of healthy gamete, players at fertilization window and what may go
wrong during the development of zygote to embryo leading to implantation failure.
We have outlined different 'windows' of vulnerability during gametogenesis
supported by evidences affecting the fertility potential of both the partners.
PMID- 28410127
TI - Oxidative stress: Major executioner in disease pathology, role in sperm DNA
damage and preventive strategies.
AB - Oxidative stress (OS) has been implicated in a wide array of diseases such as
neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and
cancer. OS is caused by an imbalance in production of Reactive Oxygen Species
(ROS) and antioxidant defenses in the cell which results in the damage of
cellular components, inactivate essential metabolic enzymes and disrupt signal
transduction pathways. OS induces peroxidative damage to the sperm plasma
membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes
dysregulation in levels of mRNAs/transcripts. OS induced sperm DNA damage is
associated with male infertility, recurrent pregnancy loss (RPL), congenital
malformations and high frequency of childhood disorders. OS induced pathologies
are caused by endogenous and exogenous factors, majority of which, are
modifiable. Antioxidant supplementation could help in relieving OS, however, its
long-term usage may disrupt the intricate oxidation-reduction balance and can
lead to "Reductive Stress". Adoption of simple lifestyle interventions may
relieve OS and can also aid in its management. This may improve overall quality
of life (QOL) and can reduce prevalence of OS induced diseases.
PMID- 28410128
TI - Genomics: Tool to predict and prevent male infertility.
AB - A large number of human diseases arise as a result of genetic abnormalities. With
the advent of improved molecular biology techniques, the genetic etiology of male
infertility is increasing. The common genetic factors responsible for male
infertility are chromosomal abnormalities, Yq microdeletion and cystic fibrosis.
These are responsible for approximately 30 percent cases of male infertility.
About 40 percent cases of male infertility are categorized as idiopathic. These
cases may be associated with genetic and genomic abnormalities. During last few
years more and more genes are implicated in male infertility leading to decline
in prevalence of idiopathic etiology. In this review we will summarize up to date
published works on genetic etiologies of male infertility including our own
works. We also briefly describe reproductive technologies used to overcome male
infertility, dangers of transmitting genetic disorders to offspring and ways to
prevent transmission of genetic disorders during assisted reproduction. At the
end we will provide our points on how genomic information can be utilized for
prediction and prevention of male infertility in coming years.
PMID- 28410129
TI - Epigenetics of reproductive infertility.
AB - Infertility is a complex pathophysiological condition. It may caused by specific
or multiple physical and physiological factors, including abnormalities in
homeostasis, hormonal imbalances and genetic alterations. In recent times various
studies implicated that, aberrant epigenetic mechanisms are associated with
reproductive infertility. There might be transgenerational effects associated
with epigenetic modifications of gametes and studies suggest the importance of
alterations in epigenetic modification at early and late stages of gametogenesis.
To determine the causes of infertility it is necessary to understand the altered
epigenetic modifications of associated gene and mechanisms involved therein. This
review is devoted to elucidate the recent mechanistic advances in regulation of
genes by epigenetic modification and emphasizes their possible role related to
reproductive infertility. It includes environmental, nutritional, hormonal and
physiological factors and influence of internal structural architecture of
chromatin nucleosomes affecting DNA and histone modifications in both male and
female gametes, early embryogenesis and offspring. Finally, we would like to
emphasize that research on human infertility by gene knock out of epigenetic
modifiers genes must be relied upon animal models.
PMID- 28410130
TI - Ghrelin doesn't limit insulin release in pregnant rats fed low protein diet.
AB - To test the hypothesis that insulin secretion in pregnant rats fed LP diet is
reduced by ghrelin signaling in pancreatic islets, we investigated plasma
insulin levels, expression of ghrelin and its receptor and glucose stimulated
insulin secretion (GSIS) of pancreatic islets in response to ghrelin. Plasma
insulin levels were lower and ghrelin receptor abundance in islets was unaltered
in LP rats. In the presence of both 2.8 and 16.7 mM glucose, GSIS was lower in LP
compared to CT rats. In the presence of 2.8 mM glucose, GSIS was unaltered by
ghrelin and its antagonist in both CT and LP rats. In the presence of 16.7 mM
glucose, GSIS in LP rats was unchanged while in CT rats was reduced by ghrelin
and reversed by ghrelin antagonist. These results indicate ghrelin signaling
inhibits GSIS of pancreatic islets in pregnant rats fed CT diet, but it is
blunted in pregnant rats fed LP diet and thus may not contribute to the reduction
of plasma insulin and GSIS of pancreatic islets in late pregnancy.
PMID- 28410132
TI - Tackling intra- and inter-tumor heterogeneity to combat triple negative breast
cancer.
AB - Rampant inter-patient and intra-tumor heterogeneity present formidable challenges
in the clinical management of triple-negative breast cancer (TNBC) and mandate a
"divide-and-conquer" approach wherein deep biomarker profiling drives patient
segmentation and development of customized treatments. Genomic and proteomic
studies have uncovered several TNBC subtypes each of which represents a distinct
disease pathobiology and harbors unique actionable targets that may illuminate
sensitivities to specific classes of therapeutics. This review details the mind
boggling complexity of TNBC, its ramifications for prognosis and therapeutic
response, and discusses what treatments might befit each TNBC subtype.
Additionally, focused efforts geared toward translating these findings into the
clinic are urged. This review also supports an evidence-based paradigm shift
towards inclusion of agents that target the mechanisms that drive intra-tumor
heterogeneity, in order to improve long-term outcomes for TNBC patients.
PMID- 28410131
TI - Substance use disorder a bio-directional subset of reward deficiency syndrome.
AB - This commentary is to inform clinicians challenged with an increase in people
seeking treatment for Substance Use Disorder (SUD), that the ninety percent
revolving door, is, in part, due to post-withdrawal, untreated neurotoxicity.
This impairment attenuates neurotransmitter signaling and compromises resting
state functional connectivity, leading to unwanted sequelae including depression,
sleep disturbances, sensation seeking, lack of satisfaction and impulsivity.
Neuroimaging studies indicate that neurobiological recovery can take years. Like
a "double edge sword" SUD has a biological bi -directional (bio-directional)
effect on the brain reward circuitry. The acute intake of psychoactive drugs
results in heightened dopaminergic activity, while, the opposite,
hypodopaminergia occurs following chronic abuse. Individuals with SUD can have a
genetic predisposition, compounded by stress and neurotoxically induced,
epigenetic insults that impact recovery from protracted abstinence. Follow-up
post -short-term recovery usually includes supportive therapies and programs like
12 -steps and other fellowships. However, relapse will usually occur if post
short-term recovery hypodopaminergia is not treated with attempts at epigenetic
manipulation of compromised brain neurochemistry using some manner of pro
dopamine regulation.
PMID- 28410133
TI - The role of lipids in host microbe interactions.
AB - Lipids are one of the major subcellular constituents and serve as signal
molecules, energy sources, metabolic precursors and structural membrane
components in various organisms. The function of lipids can be modified by
multiple biochemical processes such as (de-)phosphorylation or (de
)glycosylation, and the organization of fatty acids into distinct cellular pools
and subcellular compartments plays a pivotal role for the morphology and function
of various cell populations. Thus, lipids regulate, for example, phagosome
formation and maturation within host cells and thus, are critical for the
elimination of microbial pathogens. Vice versa, microbial pathogens can
manipulate the lipid composition of phagosomal membranes in host cells, and thus
avoid their delivery to phagolysosomes. Lipids of microbial origin belong also to
the strongest and most versatile inducers of mammalian immune responses upon
engagement of distinct receptors on myeloid and lymphoid cells. Furthermore,
microbial lipid toxins can induce membrane injuries and cell death. Thus, we will
review here selected examples for mutual host-microbe interactions within the
broad and divergent universe of lipids in microbial defense, tissue injury and
immune evasion.
PMID- 28410134
TI - Pathogen-associated regulatory non-coding RNAs and oncogenesis.
AB - Among all new cancer cases in 2012, on average, 15.4% were caused by Helicobacter
pylori or oncoviruses, including Epstein-Barr virus, human papillomavirus,
hepatitis B virus, hepatitis C viruses, Kaposi sarcoma-associated herpesvirus and
human T-lymphotropic virus. These pathogens encode a variety of non-coding RNAs,
which are important cofactors for oncogenesis. In this review, we focus on recent
developments in the study of long and small non-protein-coding RNAs, including
microRNAs, of oncogenic pathogens, and discuss their mechanisms of action in the
multiple steps of oncogenesis.
PMID- 28410135
TI - Custom-built tools for the study of deer antler biology.
AB - Deer antlers can be developed into multiple novel models to study growth and
development of tissues for biomedical research. To facilitate this process, we
have invented and further refined five custom-built tools through three decades
of antler research. These are: 1. Pedicle growth detector to pinpoint the timing
when pedicle growth is initiated, thus stimuli for pedicle and first antler
formation can be investigated and identified. 2. Thin periosteum slice cutter to
thinly slice (0.2mm or 0.7 mm thick) a whole piece of antlerogenic periosteum
(AP) or pedicle periosteum (PP), which facilitates gene delivery into cells
resident in these tissues, thus making transgenic antlers possible. 3. The porous
periosteum multi-needle punch to effectively loosen the dense AP or PP tissue.
This allows most cells of the periosteum to come into direct contact with
treating solutions, thus making artificial manipulation of antler development
possible. 4. The intra-dermal pocket maker to cut the thin dermal tissue (less
than 2 mm in thickness) of a male deer calf horizontally into two layers to make
an intra-dermal pocket. This allows loading of AP tissue intra-dermally to test
the theory of "antler stem cell niche" in vivo. 5. The sterile periosteum
sampling system to allow aseptic collection of the AP, PP or the antler growth
centre tissue on farm, thus allowing antler generation, regeneration or rapid
growth to be investigated in vitro. Overall, we believe the application of
contemporary cellular and molecular biological techniques coupled with these
custom-built tools would greatly promote the establishment of this unique and
novel model for the benefits of biomedical research, and hence human health.
PMID- 28410136
TI - Directed connectivity of brain default networks in resting state using GCA and
motif.
AB - Nowadays, there is a lot of interest in assessing functional interactions between
key brain regions. In this paper, Granger causality analysis (GCA) and motif
structure are adopted to study directed connectivity of brain default mode
networks (DMNs) in resting state. Firstly, the time series of functional magnetic
resonance imaging (fMRI) data in resting state were extracted, and the causal
relationship values of the nodes representing related brain regions are analyzed
in time domain to construct a default network. Then, the network structures were
searched from the default networks of controls and patients to determine the
fixed connection mode in the networks. The important degree of motif structures
in directed connectivity of default networks was judged according to p-value and
Z-score. Both node degree and average distance were used to analyze the effect
degree an information transfer rate of brain regions in motifs and default
networks, and efficiency of the network. Finally, activity and functional
connectivity strength of the default brain regions are researched according to
the change of energy distributions between the normals and the patients' brain
regions. Experimental results demonstrate that, both normal subjects and stroke
patients have some corresponding fixed connection mode of three nodes, and the
efficiency and power spectrum of the patient's default network is somewhat lower
than that of the normal person. In particular, the Right Posterior Cingulate
Gyrus (PCG.R) has a larger change in functional connectivity and its activity.
The research results verify the feasibility of the application of GCA and motif
structure to study the functional connectivity of default networks in resting
state.
PMID- 28410137
TI - FLAG-tagged CD19-specific CAR-T cells eliminate CD19-bearing solid tumor cells in
vitro and in vivo.
AB - Autologous T cells expressing chimeric antigen receptors (CARs) specific for CD19
have demonstrated remarkable efficacy as therapeutics for B cell malignancies. In
the present study, we generated FLAG-tagged CD19-specific CAR-T cells (CD19-FLAG)
and compared them to their non-tagged counterparts for their effects on solid and
hematological cancer cells in vitro and in vivo. For solid tumors, we used HeLa
cervical carcinoma cells engineered to overexpress CD19 (HeLa-CD19), and for
hematological cancer we used Raji Burkitt's lymphoma cells, which endogenously
express CD19. Like non-tagged CD19 CAR-T cells, CD19-FLAG CAR-T cells expanded in
culture >100-fold and exhibited potent cytolytic activity against both HeLa-CD19
and Raji cells in vitro. CD19-FLAG CAR-T cells also secreted significantly more
IFN-gamma and IL-2 than the control T cells. In vivo, CD19-FLAG CAR-T cells
significantly blocked the growth of HeLa-CD19 solid tumors, increased tumor
cleaved caspase-3 levels, and expanded systemically. CD19-FLAG CAR-T cells also
significantly reduced Raji tumor burden and extended mouse survival. These
results demonstrate the strong efficacy of FLAG-tagged CD19 CAR-T cells in solid
and hematological cancer models.
PMID- 28410138
TI - Clinical, functional, behavioural and epigenomic biomarkers of obesity.
AB - Overweight and obesity are highly prevalent conditions worldwide, linked to an
increased risk for death, disability and disease due to metabolic and biochemical
abnormalities affecting the biological human system throughout different domains.
Biomarkers, defined as indicators of biological processes in health and disease,
relevant for body mass excess management have been identified according to
different criteria, including anthropometric and molecular indexes, as well as
physiological and behavioural aspects. Analysing these different biomarkers, we
identified their potential role in diagnosis, prognosis and treatment. Epigenetic
biomarkers, cellular mediators of inflammation and factors related to microbiota
host interactions may be considered to have a theranostic value. Though, the
molecular processes responsible for the biological phenomenology detected by the
other analysed markers, is not clear yet. Nevertheless, these biomarkers possess
valuable diagnostic and prognostic power. A new frontier for theranostic
biomarkers can be foreseen in the exploitation of parameters defining behaviours
and lifestyles linked to the risk of obesity, capable to describe the effects of
interventions for obesity prevention and treatment which include also behaviour
change strategies.
PMID- 28410139
TI - Exosomes-based biomarker discovery for diagnosis and prognosis of prostate
cancer.
AB - African American men in the United States have higher incidence and mortality
rates due to prostate cancer (PCa) compared to other races. In 2016 alone, nearly
30,000 cases of PCa in African American men were diagnosed and 4,450 men died
from PCa. The underlying reasons for this health disparity in PCa are complex and
include social, economic, and biologic determinants. To reduce or eliminate this
health disparity, we must better understand the biology of the disease in African
Americans and then develop novel diagnostic and prognostic biomarkers useful for
timely and effective treatment decisions. Recently, there has been remarkable
progress in understanding the role of exosomes (vesicles of 30-150 nm diameter)
in cancer development and progression. Exosomes are loaded with unique cargo,
including proteins, nucleic acids, lipids, and metabolites, that could predict
the cells of their origin. Therefore, circulating exosomes in cancer patients are
being used as a type of biopsy to identify novel biomarkers for early diagnosis,
prognosis, and therapeutics. In this review, we discuss the promising use of
exosomes to (a) identify race-related unique biological features of PCa, and (b)
discover novel biomarkers for better diagnosis and prognosis of PCa, with the
goal of reducing cancer health disparities.
PMID- 28410140
TI - Pathway-based classification of breast cancer subtypes.
AB - Cancer heterogeneity represents a major hurdle in the development of effective
theranostic strategies, as it prevents to devise unique and maximally efficient
diagnostic, prognostic and therapeutic procedures even for patients affected by
the same tumor type. Computational techniques can nowadays leverage the huge and
ever increasing amount of (epi)genomic data to tackle this problem, therefore
providing new and valuable instruments for decision support to biologists and
pathologists, in the broad sphere of precision medicine. In this context, we here
introduce a novel cancer subtype classifier from gene expression data and we
apply it to two different Breast Cancer datasets, from TCGA and GEO repositories.
The classifier is based on Support Vector Machines and relies on the information
about the relevant pathways involved in breast cancer development to reduce the
huge variable space. Among the main results, we show that the classifier accuracy
is preserved at excellent values even when the variable space is reduced by a 20
fold, hence providing a precious tool for cancer patient profiling even in case
of limited experimental resources.
PMID- 28410141
TI - FDG PET/CT as theranostic imaging in diagnosis of non-small cell lung cancer.
AB - Objective of this work was to evaluate the role of 18F-fluorodeoxyglucose (FDG)
positron-emission tomography features as theranostic imaging biomarkers in non
small cell lung cancer. In a retrospective protocol, 31 stage I-III NSCLC
patients were enrolled. Patients underwent FDG PET/CT for staging purposes before
surgery and were followed for two years after surgery. PET images were
quantitatively analyzed. For the primary lesion, metabolic tumour volume, maximum
standardized uptake value (SUV), SUV corrected for partial volume effect, total
lesion glycolysis, 14 histogram and four shape-and-size features were extracted
as PET imaging features. PET features were correlated with histology and 2-year
disease-free survival (DFS). Significant correlations were found between grading,
T parameter, N status, pathological stage and different FDG PET features.
Histogram-based features "energy" and "kurtosis" resulted to be predictive for
DFS. The cut-off value identified for "kurtosis" was able to separate the
adenocarcinoma patients with different outcomes. FDG PET features are able to
characterize lung cancer lesions, suggesting the possibility of reliable "imaging
biopsy", and have a predictive role in adenocarcinoma patients undergoing
surgery.
PMID- 28410142
TI - Theranostic biomarkers in hypertrophic cardiomyopathy: insights in a long road
ahead.
AB - The study of biomarkers and their related signalling pathways has allowed the
development of new therapeutic strategies in a range of disorders. However, in
hypertrophic cardiomyopathy (HCM), which is the most common hereditary cardiac
disease, there are many potential biomarkers described, but their specificity and
applicability for HCM remains an open field. The aim of the present review is to
provide an overview of molecules that could give some insight into the
pathophysiologic mechanisms underlying HCM, especially to those with
"theranostic" - a combination of diagnostics and therapy - potential. The
clinical and pre-clinical state of the art and theranostic perspectives of this
topic will be part of the current discussion. The better understanding of this
subject would provide an algorithm, to optimize the integration of diagnosis,
prognostics and therapeutics findings in HCM, leading to a tailored approach for
this pathology.
PMID- 28410143
TI - Targeted radionuclide therapy: frontiers in theranostics.
AB - The concept of targeted radionuclide therapy (TRT) relies on the use of injected
nuclear medicine as treating agents, targeted at the cellular or molecular level.
The growth of the interest in TRT was stimulated by the advances in radionuclide
production and labeling as well as by the improvement in the knowledge of
appropriate and specific molecular targets. In recent years, different studies on
TRT were focused on the evaluation of radionuclide compounds able to combine
imaging of the disease with TRT, in a theranostic approach. This approach is of
particular interest towards the personalization of treatments, allowing both the
baseline characterization of oncological pathologies and treatment optimization
by correct dosimetric calculation as well as therapy monitoring. This paper
presents a review of recent literature on TRT, with a particular focus on
clinical applications promoting such a theranostic approach, showing the impact
of the synergy of diagnostic imaging and therapeutics.
PMID- 28410144
TI - Cardiotoxicity in oncology and coronary microcirculation: future challenges in
theranostics.
AB - Many of the patients undergoing chemotherapy or radiotherapy for cancer are at
increased risk of developing cardiovascular diseases. Recent evidence suggests
that cardiac dysfunction and subsequent heart failure are mainly due to vascular
toxicity rather than only to due to myocyte toxicity. However, not all of the
vascular toxicity of cancer therapies can be explained by epicardial coronary
artery disease. In fact, in the last decades, it has been found that myocardial
ischemia may occur as a consequence of structural or functional dysfunction of
the complex network of vessels, which cannot be seen by a coronary angiography:
the coronary microcirculation. Nowadays many diagnostic and therapeutic options
are available both in coronary microvascular dysfunction and cardio-oncology. Aim
of this review is to suggest future theranostic implications of the relationship
between cardiotoxicity in oncology and coronary microvascular dysfunction,
showing common pathophysiologic mechanisms, proposing new diagnostic approaches
and therapeutic options for cardioprotection.
PMID- 28410145
TI - A review of computational approaches detecting microRNAs involved in cancer.
AB - MicroRNAs (miRNAs) are small non-coding RNAs playing an essential role in gene
expression regulation. Multiple studies have demonstrated that miRNAs are
dysregulated in cancer initiation and progression, pointing out their potential
as biomarkers for diagnosis, prognosis and response to treatment. With the
introduction of high-throughput technologies several computational approaches
have been proposed to identify cancer-associated miRNAs. Here, we present a
systematic and comprehensive overview of the current knowledge concerning the
computational detection of miRNAs involved in tumor onset and subtyping, with
possible theranostic employment. An overview of the state of art in this field is
thus proposed with the aim of supporting researchers, especially experimentalists
and pathologists, in choosing the optimal approach for their case of study.
PMID- 28410146
TI - NOK mediates glycolysis and nuclear PDC associated histone acetylation.
AB - NOK is a potent oncogene that can transform normal cells to cancer cells. We
hypothesized that NOK might impact cancer cell metabolism and histone
acetylation. We show that NOK localizes in the mitochondria, and while it
minimally impacts tricarboxylic acid (TCA) cycle, it markedly inhibits the
process of electron transport and oxidative phosphorylation processes and
dramatically enhances aerobic glycolysis in cancer cells. NOK promotes the
mitochondrial-nuclear translocation of pyruvate dehydrogenase complex (PDC), and
enhances histone acetylation in the nucleus. Together, these findings show that
NOK mediates glycolysis and nuclear PDC associated histone acetylation.
PMID- 28410148
TI - Remodeling of tick cytoskeleton in response to infection with Anaplasma
phagocytophilum.
AB - The obligate intracellular pathogen Anaplasma phagocytophilum infects vertebrate
and tick hosts. In this study, a genome-wide search for cytoskeleton components
was performed in the tick vector, Ixodes scapularis. The available
transcriptomics and proteomics data was then used to characterize the mRNA and
protein levels of I. scapularis cytoskeleton components in response to A.
phagocytophilum infection. The results showed that cytoskeleton components
described in other model organisms were present in the I. scapularis genome. One
type of intermediate filaments (lamin), a family of septins that was recently
implicated in the cellular response to intracellular pathogens, and several
members of motor proteins (kinesins and dyneins) that could be implicated in the
cytoplasmic movements of A. phagocytophilum were found. The results showed that
levels of tubulin, actin, septin, actin-related proteins and motor proteins were
affected by A. phagocytophilum, probably to facilitate infection in I.
scapularis. Functional studies demonstrated a role for selected cytoskeleton
components in pathogen infection. These results provided a more comprehensive
view of the cytoskeletal components involved in the response to A.
phagocytophilum infection in ticks.
PMID- 28410149
TI - Rerouting the traffic from a virus perspective.
AB - Viruses are important human and animal pathogens causing disease that affect
global health and the economy. One outcome of many virus infections is the
regulation of cellular trafficking machinery. Viral proteins recruit and interact
with cellular trafficking proteins to divert the normal trafficking of key
proteins or to induce the formation of novel membrane structures in the host
cell. These alterations often increase replication efficiency by mislocalizing
immune regulators or restriction factors ot by creating platforms for replication
and assembly of new virus particles. Our knowledge of how viruses interact with
the cellular trafficking machinery is still limited and furthering this
understanding will be important for the future development of prophylactic and
therapeutic treatments. This review provides a glimpse of the types of interplay
between viral and cellular factors that result in a disruption of cellular
trafficking or modifications to cellular membranes.
PMID- 28410150
TI - Platelet toll-like receptors in thromboinflammation.
AB - Besides their undiscussed role in hemostasis and thrombosis, platelets are also
key effector cells capable of assisting and modulating inflammatory reactions and
immune responses. Platelets play a sentinel role in immune surveillance by
recognizing danger signals from pathogens and cell damage through the expression
of toll-like receptors (TLRs) on its surface and internal compartments. Platelets
express all 10 TLRs transcripts and its signalosome, including adaptor proteins
and transcription factors. The activation of these receptors in platelets
triggers hemostatic and inflammatory responses which participate in the host's
response to bacterial and viral infections, linking thrombosis with infection and
immunity. Among the responses elicited by the activation of platelet TLRs are
platelet adhesion and aggregation, formation of mixed platelet-leukocyte
aggregates, expression and secretion of cytokines and quemokines, and thrombin
generation. TLRs also are expressed in megakaryocytes, and their activation
regulates not only platelet biogenesis, but also pro-inflammatory and antiviral
responses. This review will focus on work that has shown the role of platelet
TLRs, mainly in thromboinflammatory responses elicited by platelets and
megakaryocytes.
PMID- 28410151
TI - Effect of ancestry on interleukin-10 haplotypes in chronic periodontitis.
AB - Chronic periodontitis is caused by an inflammatory reaction of the periodontal
tissues and alveolar bone. This inflammation is caused by periodontopathic
bacteria located in the subgingival biofilm, resulting in inflammatory reactions
that may lead to loss of attachment. This tissue destruction is a consequence of
host immune and inflammatory responses to specific periodontal pathogens and
their metabolic products. Cytokines modulate the immune response, altering its
efficiency in the competition against pathogens and increasing periodontal
susceptibility. This study investigated genetic polymorphisms in Interleukin 10
(A-1082G, C-819T and C-592A) in 205 individuals from an admixed Brazilian
population. A significantly increased risk of developing chronic periodontitis
was observed in individuals with low IL-10 production and Amerindian ancestry.
These results suggest that the polymorphisms A-1082G, C-819T, and C-592A, which
are associated with ancestry, are involved in the susceptibility to the
development of chronic periodontitis in an admixed northern Brazilian population.
PMID- 28410152
TI - Fungal immunomodulatory proteins in the context of biomedicine.
AB - Fungi represent a large group of biodiverse microorganisms with potential
applications ranging from industrial fields to the treatment for human diseases.
A large number of pharmacologically active compounds including terpenoids,
polysaccharides and proteins have been derived from these microorganisms. Fungal
Immunomodulatory Proteins (FIPs) are a group of active compounds that are being
considered for the treatment of asthma, allergy, autoimmune diseases and cancer.
Here, we discuss the discovery, heterologous production bioactive mechanisms of
action and their potential use in biomedicine.
PMID- 28410147
TI - The roles of microglia/macrophages in tumor progression of brain cancer and
metastatic disease.
AB - Malignant brain tumors and brain metastases are highly aggressive diseases that
are often resistant to treatment. Consequently, the current prognosis of patients
with brain tumors and metastases is dismal. Activated microglia and macrophages
are often observed in close proximity to or within the malignant tumor masses,
suggesting that microglia/macrophages play an important role in brain tumor
progression. Microglia, being resident macrophages of the central nervous system,
form a major component of the brain immune system. They exhibit anti-tumor
functions by phagocytosis and the release of cytotoxic factors. However, these
microglia/macrophages can be polarized into becoming tumor-supportive and
immunosuppressive cells by certain tumor-derived soluble factors, thereby
promoting tumor maintenance and progression. The activated microglia/macrophages
also participate in the process of tumor angiogenesis, metastasis, dormancy, and
relapse. In this review, we discuss the recent literature on the dual roles of
microglia/macrophages in brain tumor progression. We have also reviewed the
effect of several well-known microglia/macrophages-derived molecules and signals
on brain tumor progression and further discussed the potential therapeutic
strategies for targeting the pro-tumor and metastatic functions of
microglia/macrophages.
PMID- 28410153
TI - The cognitive dysregulation of Internet addiction and its neurobiological
correlates.
AB - Individuals with Internet addiction (IA) show loss of control and recurring
maladaptive Internet use. This condition has negative consequences and causes
significant psychosocial distress. Here, we review neurobiological changes in
four key paradigms in cognitive domain in IA including reward processing,
impulsivity, cue reactivity, and decision-making. IA is associated with
alterations in prefrontal-cingulate region activation during the inhibition of
inappropriate responses. Such patterns are also observed in cue-reactivity
paradigm tasks, suggesting a relationship with loss of control and deficits in
the control of cue-eliciting behavior. Individuals with IA exhibit heightened
reward prediction, devalue negative outcomes and have a higher risk-taking
propensity under ambiguous situations. In conclusion, addictive use of the
Internet is associated with deficits in cognitive-emotional processing, aberrant
sensitivity to rewards and Internet-related cues, poor impulse control, and
impaired decision-making. There is a need to examine neural underpinnings of
these aberrant behaviors and neurobiological-cognitive perspective in IA.
PMID- 28410154
TI - Current status of a unique vaccine preventing pregnancy.
AB - The ability of a vaccine linking beta hCG to a carrier to generate antibodies
against hCG, its reversibility and safety was established by Phase I clinical
trials conducted in India, Finland, Sweden, Chile and Brazil. Employing a hetero
species dimer (beta hCG-alphaoLH) linked to tetanus toxoid further improved the
immunogenicity of the vaccine. Phase II clinical trials showed that anti-hCG
titres above 50 ng/ml prevented pregnancy of sexually active fertile women
without derangement of ovulation and menstrual regularity. On decline of
antibodies, women conceived again to give birth to normal progeny. A genetically
engineered vaccine consisting of beta hCG linked to B subunit of heat labile
enterotoxin of E. coli has been made. It is expressed as DNA as well as protein.
Priming with DNA followed by protein version of the vaccine generates very high
titres against hCG in mice. Extensive toxicology studies in 2 species of rodents,
and marmosets have shown complete safety of the vaccine. The vaccine is cleared
for Clinical trials by the National Review committee on Genetic Manipulation and
Drugs Controller General of India.
PMID- 28410155
TI - The puzzle of bakanae disease through interactions between Fusarium fujikuroi and
rice.
AB - Bakanae disease, one of the most noteworthy seedborne rice diseases, is caused by
Fusarium fujikuroi, a member of the Gibberella fujikuroi species complex. The
decreasing availability of chemical seed-dressing products over the last few
years has raised the concerns of rice seed companies regarding bakanae disease.
Therefore, new research trends require a deeper investigation into the main
aspects of bakanae disease through interactions between rice and F. fujikuroi, in
order to find new resistant or tolerant cultivars and alternative bakanae disease
control strategies, as well as to develop more sensitive molecular diagnostic
techniques. Here, some new aspects of F. fujikuroi epidemiology and
pathogenicity, as well as its interactions with rice, are reported, and recent
approaches applied to control bakanae disease are summarized.
PMID- 28410156
TI - Diffuse gingival hyperplasia. Ramus radiolucency.
PMID- 28410157
TI - Needs and Preferences of Partners of Cancer Patients Regarding a Web-Based
Psychological Intervention: A Qualitative Study.
AB - BACKGROUND: Evidence-based, easily accessible, supportive interventions for
partners of cancer patients are limited, despite the fact that they often suffer
from diminished emotional, social, physical, and relational functioning. To
develop a new intervention that will fit their demands, it is important to
consult potential users. OBJECTIVE: To examine partners' interest in a Web-based
psychological intervention and to identify their needs and wishes regarding such
an intervention. METHODS: Semistructured interviews were conducted with 16
partners of cancer patients, who varied in terms of age, gender, education,
employment, type, and stage of disease. Partners were asked (1) whether they
would use a psychological Web-based intervention and which preconditions (maximum
time, structure, participate alone or with their partner) it should meet; (2)
which functionalities (information, peer support, online psychological
counseling) the intervention should contain; and (3) which topics (eg, taking
care of oneself) should be addressed. Data were coded by 2 coders independently.
RESULTS: The need for a Web-based intervention varied. Arguments for being
interested in a Web-based intervention included the need for acknowledgement; the
need for someone they could talk to; and the need for information, tips, and
support. Based on their experiences as a partner of a cancer patient,
participants would prefer an intervention that is not too time-consuming (about 1
2 hours a week) and which is based on a "step-by-step" approach, meaning that the
content of the intervention should match the stage of their partner's disease.
Also, they would prefer a positive approach, which means that the intervention
should be a source of hope and energy. Most participants stated that they would
prefer to participate without their ill spouse, because they do not want to
burden their partners with their own problems. An intervention should contain
information and optional peer support. Participants' opinions about online
psychological counseling in the intervention were divided. Arguments for online
psychological counseling were that a professional could check on them and they
were able to ask questions. Arguments against online counseling were that
partners were not in need for guidance or they had enough support from usual
care. Topics with the highest priority were "coping with feelings and emotions,"
"should I or shouldn't I spare my partner?," "communicating with each other,"
"asking for help and refusing help," and "moving on with life after cancer
treatment." Furthermore, participants suggested additional topics of "dare to
enjoy" and "acceptance of the patient's disease." CONCLUSIONS: A Web-based
intervention can be a valuable addition to existing support initiatives for
partners of cancer patients. This study provides important information about the
content and form of such an intervention. Flexibility and a positive approach
seem to be the most important features.
PMID- 28410158
TI - Efficacy of a Mobile-Enabled Web App (iCanFit) in Promoting Physical Activity
Among Older Cancer Survivors: A Pilot Study.
AB - BACKGROUND: The benefits of physical activity for cancer survivors are well
documented. However, few older cancer survivors are engaged in regular physical
activity. Mobile technologies may be an effective method to deliver physical
activity promotion programs for older cancer survivors. iCanFit, a mobile-enabled
Web-based app, was developed based on formative research and usability testing.
This app includes interactive features of physical activity, goal setting and
tracking, and receiving personalized visual feedback. OBJECTIVE: The aim of this
study is to pilot test the initial efficacy of iCanFit. METHODS: Older cancer
survivors (N=30) were recruited online through our collaborative partnership with
a cancer survivor's organization. After the participants completed an online
baseline survey, they were asked to use the iCanFit website. Instructional videos
on how to use the web app were available on the website. Participants were asked
to complete a follow-up survey 2-3 months later. Participants' physical activity,
quality of life, and their experience with iCanFit were measured. RESULTS: A
total of 30 participants completed the baseline survey, and 26 of them (87%,
26/30) also completed a follow-up survey 2-3 months later. The median age of
participants was 69 years (range 60-78). Participants' quality of life and
engagement in regular physical activity improved significantly after the use of
iCanFit. Participants indicated a general affinity towards the key function
"Goals" in iCanFit, which motivated continued activity. They also provided
suggestions to further improve the app (eg, adding a reminder functionality,
easier or alternative ways of entering activities). CONCLUSION: The interactive
Web-based app iCanFit has demonstrated initial efficacy. Even though our study
was limited by a small sample size, convenience sampling, and a short follow-up
period, results suggest that using mobile tools to promote physical activity and
healthy living among older cancer survivors holds promise. Next steps include
refining iCanFit based on users' feedback and developing versatile functionality
to allow easier physical activity goal setting and tracking. We also call for
more studies on developing and evaluating mobile and web apps for older cancer
survivors.
PMID- 28410159
TI - Defining the Role of the Online Therapeutic Facilitator: Principles and
Guidelines Developed for Couplelinks, an Online Support Program for Couples
Affected by Breast Cancer.
AB - Development of psychological interventions delivered via the Internet is a
rapidly growing field with the potential to make vital services more accessible.
However, there is a corresponding need for careful examination of factors that
contribute to effectiveness of Internet-delivered interventions, especially given
the observed high dropout rates relative to traditional in-person (IP)
interventions. Research has found that the involvement of an online therapist in
a Web-based intervention reduces treatment dropout. However, the role of such
online therapists is seldom well articulated and varies considerably across
programs making it difficult to discern processes that are important for online
therapist involvement.In this paper, we introduce the concept of "therapeutic
facilitation" to describe the role of the online therapist that was developed and
further refined in the context of a Web-based, asynchronous psychosocial
intervention for couples affected by breast cancer called Couplelinks.
Couplelinks is structured into 6 dyadic learning modules designed to be completed
on a weekly basis in consultation with a facilitator through regular,
asynchronous, online text-based communication.Principles of therapeutic
facilitation derived from a combination of theory underlying the intervention and
pilot-testing of the first iteration of the program are described. Case examples
to illustrate these principles as well as commonly encountered challenges to
online facilitation are presented. Guidelines and principles for therapeutic
facilitation hold relevance for professionally delivered online programs more
broadly, beyond interventions for couples and cancer.
PMID- 28410160
TI - The Impact of Advice Seekers' Need Salience and Doctors' Communication Style on
Attitude and Decision Making: A Web-Based Mammography Consultation Role Play.
AB - BACKGROUND: Patients and advice seekers come to a medical consultation with
typical needs, and physicians require adequate communication skills in order to
address those needs effectively. It is largely unclear, however, to what extent
advice seekers' attitudes toward a medical procedure or their resulting decisions
are influenced by a physician's communication that ignores or explicitly takes
these needs into account. OBJECTIVE: This experimental study tested how advice
seekers' salient needs and doctor's communication styles influenced advice
seekers' attitudes toward mammography screening and their decision whether or not
to participate in this procedure. METHODS: One hundred women (age range 20-47
years, mean 25.22, SD 4.71) participated in an interactive role play of an online
consultation. During the consultation, a fictitious, program-controlled physician
provided information about advantages and disadvantages of mammography screening.
The physician either merely communicated factual medical information or made
additional comments using a communication style oriented toward advice seekers'
typical needs for clarity and well-being. Orthogonal to this experimental
treatment, participants' personal needs for clarity and for well-being were
either made salient before or after the consultation with a needs questionnaire.
We also measured all participants' attitudes toward mammography screening and
their hypothetical decisions whether or not to participate before and after the
experiment. RESULTS: As assumed, the participants expressed strong needs for
clarity (mean 4.57, SD 0.42) and for well-being (mean 4.21, SD 0.54) on 5-point
Likert scales. Making these needs salient or not revealed significant interaction
effects with the physician's communication style regarding participants' attitude
change (F1,92=7.23, P=.009, eta2=.073) and decision making (F1,92=4.43, P=.038,
eta2=.046). Those participants whose needs were made salient before the
consultation responded to the physician's communication style, while participants
without salient needs did not. When the physician used a need-oriented
communication style, those participants with salient needs had a more positive
attitude toward mammography after the consultation than before (mean 0.13, SD
0.54), while they changed their attitude in a negative direction when confronted
with a purely fact-oriented communication style (mean -0.35, SD 0.80). The same
applied to decision modification (need-oriented: mean 0.10, SD 0.99; fact
oriented: mean -0.30, SD 0.88). CONCLUSIONS: The findings underline the
importance of communicating in a need-oriented style with patients and advice
seekers who are aware of their personal needs. Ignoring the needs of those people
appears to be particularly problematic. So physicians' sensitivity for advice
seekers' currently relevant needs is essential.
PMID- 28410161
TI - Effect of Web-Based Versus Paper-Based Questionnaires and Follow-Up Strategies on
Participation Rates of Dutch Childhood Cancer Survivors: A Randomized Controlled
Trial.
AB - BACKGROUND: Questionnaires are widely used in survey research, especially in
cohort studies. However, participation in questionnaire studies has been
declining over the past decades. Because high participation rates are needed to
limit the risk of selection bias and produce valid results, it is important to
investigate invitation strategies which may improve participation. OBJECTIVES:
The purpose of this study is to investigate the effect of Web-based versus paper
based questionnaires on participation rates in a questionnaire survey on late
effects among childhood cancer survivors (CCSs). METHODS: A total of 750 CCSs
were randomized across 3 study arms. The initial invitation in study arms 1 and 2
consisted of a Web-based questionnaire only, whereas in study arm 3 this
invitation was complemented with a paper-based version of the questionnaire. The
first postal reminder, sent to the nonresponding CCSs in all 3 study arms,
consisted of either a reminder letter only (study arms 1 and 3) or a reminder
letter complemented with a paper-based questionnaire (study arm 2). The second
postal reminder was restricted to CCSs in study arms 1 and 2, with only those in
study arm 1 also receiving a paper-based questionnaire. CCSs in study arm 3
received a second reminder by telephone instead of by mail. In contrast to CCSs
in study arm 3, CCSs in study arms 1 and 2 received a third reminder, this time
by telephone. Results: Overall, 58.1% (436/750) of the CCSs participated in the
survey. Participation rates were equal in all 3 study arms with 57.4% (143/249)
in arm 1, 60.6% (152/251) in arm 2, and 56.4% (141/250) in arm 3 (P=.09).
Participation rates of CCSs who received an initial invitation for the Web-based
questionnaire only and CCSs who received an invitation to complete either a paper
based or Web-based questionnaire did not differ (P=.55). After the first postal
reminder, participation rates of CCSs invited for the Web-based questionnaire
only also did not differ compared with CCSs invited for both the Web-based and
paper-based questionnaires (P=.48). In general, CCSs preferred the paper-based
over the Web-based questionnaire, and those completing the paper-based
questionnaire were more often unemployed (P=.004) and lower educated (P<.001).
CONCLUSION: Invitation strategies offering a Web-based questionnaire without a
paper-based alternative at first invitation can be used without compromising
participation rates of CCS. Offering the choice between paper- and Web-based
questionnaires seems to result in the highest accrual participation rate. Future
research should look into the quality of the data delivered by both
questionnaires filled in by respondents themselves. TRIAL REGISTRATION:
International Standard Randomized Controlled Trial Number (ISRCTN): 84711754;
http://www.controlled-trials.com/ISRCTN84711754 (Archived by WebCite at
http://www.webcitation.org/6c9ZB8paX).
PMID- 28410162
TI - Lifestyle Modification Experiences of African American Breast Cancer Survivors: A
Needs Assessment.
AB - BACKGROUND: Little is known about the rates of obesity among African American
(AA) breast cancer survivors (BCSs), the availability and use of lifestyle
modification methods suitable for this population, and the impact of changes in
dietary intake and physical activity on health-related quality of life (HR-QoL).
OBJECTIVE: The objectives of the study were to describe obesity rates, dietary
intake, and physical activity as lifestyle modification strategies; examine
predictors of engagement in these strategies post diagnosis; and learn more about
salient features of lifestyle interventions from AA BCSs participating in a
breast cancer support group. METHODS: The needs assessment included four
components: (1) a literature review to determine existing lifestyle modification
strategies of AA BCSs; (2) secondary data analysis of the 2010 National Health
Interview Survey, Cancer Control Supplement to examine HR-QoL; (3)
administration, to 200 AA BCSs, of an assessment tool relating to weight and
breast cancer history, dietary intake, and physical activity through a variety of
approaches (eg, Internet, mail, in-person, and telephone); and (4) focus group
discussions to frame lifestyle interventions. RESULTS: Preliminary findings
indicate that AA BCSs are underrepresented in lifestyle intervention research,
have disparities in HR-QoL outcomes, do not meet current cancer prevention
guidelines, and have recommendations for effective strategies for lifestyle
modification. CONCLUSIONS: As analyses of the needs assessment are completed, the
research team is partnering with community coalitions and breast cancer support
groups in Miami, Chicago, Houston, Los Angeles, and Philadelphia to develop
community-engaged intervention approaches for promoting adherence to cancer
prevention guidelines.
PMID- 28410163
TI - Evaluation of a Web-Based App Demonstrating an Exclusionary Algorithmic Approach
to TNM Cancer Staging.
AB - BACKGROUND: TNM staging plays a critical role in the evaluation and management of
a range of different types of cancers. The conventional combinatorial approach to
the determination of an anatomic stage relies on the identification of distinct
tumor (T), node (N), and metastasis (M) classifications to generate a TNM
grouping. This process is inherently inefficient due to the need for scrupulous
review of the criteria specified for each classification to ensure accurate
assignment. An exclusionary approach to TNM staging based on sequential
constraint of options may serve to minimize the number of classifications that
need to be reviewed to accurately determine an anatomic stage. OBJECTIVE: Our aim
was to evaluate the usability and utility of a Web-based app configured to
demonstrate an exclusionary approach to TNM staging. METHODS: Internal medicine
residents, surgery residents, and oncology fellows engaged in clinical training
were asked to evaluate a Web-based app developed as an instructional aid
incorporating (1) an exclusionary algorithm that polls tabulated classifications
and sorts them into ranked order based on frequency counts, (2) reconfiguration
of classification criteria to generate disambiguated yes/no questions that
function as selection and exclusion prompts, and (3) a selectable grid of TNM
groupings that provides dynamic graphic demonstration of the effects of
sequentially selecting or excluding specific classifications. Subjects were asked
to evaluate the performance of this app after completing exercises simulating the
staging of different types of cancers encountered during training. RESULTS:
Survey responses indicated high levels of agreement with statements supporting
the usability and utility of this app. Subjects reported that its user interface
provided a clear display with intuitive controls and that the exclusionary
approach to TNM staging it demonstrated represented an efficient process of
assignment that helped to clarify distinctions between tumor, node, and
metastasis classifications. High overall usefulness ratings were bolstered by
supplementary comments suggesting that this app might be readily adopted for use
in clinical practice. CONCLUSIONS: A Web-based app that utilizes an exclusionary
algorithm to prompt the assignment of tumor, node, and metastasis classifications
may serve as an effective instructional aid demonstrating an efficient and
informative approach to TNM staging.
PMID- 28410164
TI - Interest in Health Behavior Intervention Delivery Modalities Among Cancer
Survivors: A Cross-Sectional Study.
AB - BACKGROUND: Effective, broad-reaching channels are important for the delivery of
health behavior interventions in order to meet the needs of the growing
population of cancer survivors in the United States. New technology presents
opportunities to increase the reach of health behavior change interventions and
therefore their overall impact. However, evidence suggests that older adults may
be slower in their adoption of these technologies than the general population.
Survivors' interest for more traditional channels of delivery (eg, clinic) versus
new technology-based channels (eg, smartphones) may depend on a variety of
factors, including demographics, current health status, and the behavior
requiring intervention. OBJECTIVE: The aim of this study was to determine the
factors that predict cancer survivors' interest in new technology-based health
behavior intervention modalities versus traditional modalities. METHODS: Surveys
were mailed to 1871 survivors of breast, prostate, and colorectal cancer.
Participants' demographics, diet and physical activity behaviors, interest in
health behavior interventions, and interest in intervention delivery modalities
were collected. Using path analysis, we explored the relationship between four
intervention modality variables (ie, clinic, telephone, computer, and smartphone)
and potential predictors of modality interest. RESULTS: In total, 1053
respondents to the survey (56.3% response rate); 847 provided complete data for
this analysis. Delivery channel interest was highest for computer-based
interventions (236/847, 27.9% very/extremely interested) and lowest for
smartphone-based interventions (73/847, 8.6%), with interest in clinic-based
(147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use
of other technology platforms, such as Web cameras and social networking sites,
was positively predictive of interest in technology-based delivery channels.
Older survivors were less likely to report interest in smartphone-based diet
interventions. Physical activity, fruit and vegetable consumption, weight status,
and age moderated relationships between interest in targeted intervention
behavior and modality. CONCLUSIONS: This study identified several predictors of
survivor interest in various health behavior intervention delivery modalities.
Overall, computer-based interventions were found to be most acceptable, while
smartphones were the least. Factors related to survivors' current technology use
and health status play a role in their interest for technology-based intervention
versus more traditional delivery channels. Future health behavior change research
in this population should consider participants' demographic, clinical, and
lifestyle characteristics when selecting a delivery channel. Furthermore, current
health behavior interventions for older cancer survivors may be best delivered
over the Internet. Smartphone interventions may be feasible in the future
following further adoption and familiarization by this particular population.
PMID- 28410165
TI - Age-Related Use and Perceptions of eHealth in Men With Prostate Cancer: A Web
Based Survey.
AB - BACKGROUND: Men with prostate cancer require ample information and support along
the continuum of care, and eHealth is one way to meet such critical information
and support needs. Currently, evidence about how age influences use and
perceptions about prostate cancer eHealth information and support is lacking.
OBJECTIVE: The aim of this paper is to explore use and perceptions about eHealth
among men living with prostate cancer. Specifically, we aimed to analyze men with
prostate cancer by age-specific cohorts to identify potential age-related
differences in use and perceptions about prostate cancer eHealth information.
METHODS: We used survey methodology to examine how men under 65 years old with
prostate cancer differ from those aged 65 years old or older in use and
perceptions about prostate cancer eHealth information and support (n=289).
RESULTS: We found that men in the younger cohort used the Internet more often to
be informed about treatment options (P=.04) and to learn more about
staging/grading (P=.01) than men in the older cohort. Results also showed
comparatively greater use of online prostate cancer information for emotional
support and encouragement by the younger as compared to the older cohort
(P=.001). Furthermore, the older cohort reported more negative psychosocial
effects of eHealth (eg, more anxious, depressed) than younger men (P=.002). We
also found that as a result of more frequent Internet use, younger men
experienced more positive psychosocial effects (eg, more informed, in control)
from accessing information about prostate cancer through eHealth channels (b=
0.10, 95% CI -0.28 to 0). CONCLUSIONS: Men with prostate cancer have different
information and support needs; our findings suggest that these needs might vary
by age. Future research is needed to unravel age-related factors underlying these
differences to be better able to tailor prostate cancer eHealth information to
men's information and support needs.
PMID- 28410166
TI - Feasibility and Preliminary Efficacy of an Online Intervention to Increase
Physical Activity in Nova Scotian Cancer Survivors: A Randomized Controlled
Trial.
AB - BACKGROUND: Physical activity (PA) behavior change interventions among cancer
survivors have used face-to-face, telephone, email, and print-based methods.
However, computer-tailored, Internet-delivered programs may be a more viable
option to achieve PA behavior change. OBJECTIVE: The objective of this study is
to test the feasibility and preliminary efficacy of a Web-based PA behavior
change program among cancer survivors. METHODS: Nova Scotian cancer survivors
(N=415) who previously expressed interest in a research study were approached.
Interested participants were asked to complete an online assessment of PA and
quality of life (QOL) before being randomized to either a theory-based PA
behavior change program using the PA tracking website UWALK (UCAN; n=48) or usual
care (UC; n=47). After the intervention (9 weeks), participants completed another
online assessment of PA and QOL as well as measures to evaluate the program and
website. Descriptive analyses from surveys and Web analytic software were used to
assess feasibility and mean change scores were used to test efficacy. RESULTS: Of
all contacted survivors, 95 (22.3%, 95/415) completed baseline measures and were
randomized with 84 (88%, 84/95) completing the 9-week assessment. The behavior
change program and website were rated highly on the satisfaction items. Average
logins were 10.3 (1.1 per week) and 26.0% (111/432) of the weekly modules were
completed. Most participants (71%, 29/41) indicated they were more aware of their
daily PA levels and 68% (28/41) found the site easily navigable. Adjusted group
differences in total exercise minutes favored the UCAN group by an increase of 42
minutes (95% CI -65 to 150; P=.44, d=0.17). Results were more pronounced, though
still nonsignificant, among those not meeting guidelines at baseline where UCAN
increased PA by 52 minutes compared to a decrease of 15 minutes in UC (adjusted
between group difference=75, 95% CI -95 to 244; P=.38, d=0.27). CONCLUSIONS: We
found that Internet-delivery may be a feasible alternative to more costly methods
to promote PA among Nova Scotian cancer survivors. Moreover, there was a trend
toward increased PA among those in the UCAN group, especially among those who
were not meeting PA guidelines at baseline. Future research should focus on
recruiting inactive cancer survivors and engaging them in the website to
determine the optimal potential of Web-based interventions for promoting PA in
cancer survivors.
PMID- 28410167
TI - YouTube Videos Related to Skin Cancer: A Missed Opportunity for Cancer Prevention
and Control.
AB - BACKGROUND: Early detection and treatment influence the mortality risk of skin
cancer. OBJECTIVE: The objective of this study was to analyze the content of the
most viewed professional and consumer videos uploaded to YouTube related to skin
cancer. METHODS: A total of 140 professional and consumer videos uploaded between
2007 and 2014 were identified and coded. Coding involved identifying and sorting
followed by gathering descriptive information, including length of the video,
number of views, and year uploaded. A dichotomous coding scheme (ie, yes or no)
was used in coding specific aspects of video content, including provision of
information, type of skin cancer, age group, family history, risk reduction, risk
factors, fear, and home remedies for skin cancer treatment. RESULTS: The majority
of videos provided information related to screening. Many consumer videos
conveyed information related to the use of a black salve as a home remedy for
skin cancer, despite the fact that there is no evidence that it is an effective
treatment. CONCLUSIONS: Research is needed to identify characteristics of videos
that are most likely to be viewed to inform the development of credible
communications.
PMID- 28410168
TI - Assessment of Cancer Survivors' Experiences of Using a Publicly Available
Physical Activity Mobile Application.
AB - BACKGROUND: Regular participation in physical activity (PA) is associated with
improved physical and psychosocial outcomes in cancer survivors. However, PA
levels are low during and after cancer treatment. Interventions to promote PA in
this population are needed. PA mobile apps are popular and have potential to
increase PA participation, but little is known about how appropriate or relevant
they are for cancer survivors. OBJECTIVE: This study aims to (1) assess
recruitment, study uptake, and engagement for a publicly available PA mobile app
(GAINFitness) intervention in cancer survivors; (2) assess cancer survivors'
attitudes towards the app; (3) understand how the app could be adapted to better
meet the needs of cancer survivors; and (4) to determine the potential for change
in PA participation and psychosocial outcomes over a 6-week period of using the
app. METHODS: The present study was a one-arm, pre-post design. Cancer survivors
(N=11) aged 33 to 62 years with a mean (SD) age of 45 (9.4), and 82% (9/11)
female, were recruited (via community/online convenience sampling to use the app
for 6 weeks). Engagement with the app was measured using self-reported frequency
and duration of usage. Qualitative semi-structured telephone interviews were
conducted after the 6-week study period and were analyzed using thematic
analysis. PA, well-being, fatigue, quality of life (QOL), sleep quality, and
anxiety and depression were self-reported at baseline and at a 6-week follow-up
using the Godin Leisure Time Exercise Questionnaire (GLTEQ), the Functional
Assessment of Cancer Therapy-General (FACT-G), the Functional Assessment of
Chronic Illness Therapy (FACIT)-Fatigue Scale Questionnaire, the Health and
Quality of Life Outcomes (EQ5D) Questionnaire, the Pittsburgh Sleep Quality Index
(PSQI), and the Hospital Anxiety and Depression Scale (HADS), respectively.
RESULTS: Of the people who responded to the study advertisement, 73% (16/22)
agreed to participate and 100% (11/11) of the participants who started the study
completed all baseline and follow-up outcome measures and the telephone
interview. On average, participants used the app twice a week for 25 minutes per
session. Four themes were identified from the qualitative interviews surrounding
the suitability of the app for cancer survivors and how it could be adapted: (1)
barriers to PA, (2) receiving advice about PA from reliable sources, (3)
tailoring the application to one's lifestyle, and (4) receiving social support
from others. Pre-post comparison showed significant increases in strenuous PA,
improvements in sleep quality, and reductions in mild PA. There were no
significant changes in moderate PA or other psychosocial outcomes. CONCLUSIONS:
All participants engaged with the app and qualitative interviews highlighted that
the app was well-received. A generic PA mobile app could bring about positive
improvements in PA participation and psychosocial outcomes among cancer
survivors. However, a targeted PA app aimed specifically towards cancer survivors
may increase the relevance and suitability of the app for this population.
PMID- 28410169
TI - Blog Posting After Lung Cancer Notification: Content Analysis of Blogs Written by
Patients or Their Families.
AB - BACKGROUND: The advent and spread of the Internet has changed the way societies
communicate. A portion of information on the Internet may constitute an important
source of information concerning the experiences and thoughts of patients and
their families. Patients and their families use blogs to obtain updated
information, search for alternative treatments, facilitate communication with
other patients, and receive emotional support. However, much of this information
has yet to be actively utilized by health care professionals. OBJECTIVE: We
analyzed health-related information in blogs from Japan, focusing on the feelings
and satisfaction levels of lung cancer patients or their family members after
being notified of their disease. METHODS: We collected 100 blogs written in
Japanese by patients (or their families) who had been diagnosed with lung cancer
by a physician. These 100 blogs posts were searchable between June 1 and June 30,
2013. We focused on blog posts that addressed the lung cancer notification event.
We analyzed the data using two different approaches (Analysis A and Analysis B).
Analysis A was blog content analysis in which we analyzed the content addressing
the disease notification event in each blog. Analysis B was patient's
dissatisfaction and anxiety analysis. Detailed blog content regarding patient's
dissatisfaction and anxiety at the individual sentence level was coded and
analyzed. RESULTS: The 100 blog posts were written by 48 men, 46 women, and 6
persons whose sex was undisclosed. The average age of the blog authors was 52.4
years. With regard to cancer staging, there were 5 patients at Stage I, 3
patients at Stage II, 14 patients at Stage III, 21 patients at Stage IV, and 57
patients without a disclosed cancer stage. The results of Analysis A showed that
the proportion of patients who were dissatisfied with the level of health care
exceeded that of satisfied patients (22% vs 8%). From the 2499 sentences in the
100 blog posts analyzed, we identified expressions of dissatisfaction and anxiety
in 495 sentences. Our results showed that there were substantially more posts
concerning "Way of living, reasons for living, set of values" and "Relationships
with medical staff (own hospital)" than in previous studies (Analysis B).
CONCLUSIONS: This study provides insight into the feelings of dissatisfaction and
anxieties held by lung cancer patients and their families, including those
regarding the "Way of living, reasons for living, set of values" and
"Relationship with medical staff (own hospital)," which were inaccessible in
previous survey analyses. When comparing information obtained from patients'
voluntary records and those from previous surveys conducted by health care
institutions, it is likely that the former would be more indicative of patients'
actual opinions and feelings. Therefore, it is important to utilize such records
as an information resource.
PMID- 28410170
TI - Patients' and Health Care Providers' Opinions on a Supportive Health App During
Breast Cancer Treatment: A Qualitative Evaluation.
AB - BACKGROUND: Health apps are increasingly being used in clinical care and may hold
significant theoretical potential. However, they are often implemented in
clinical care before any research has been done to confirm actual benefits for
patients, physicians, and researchers. OBJECTIVE: This study aimed to explore
experiences of patients and health care providers with the use of a supportive
breast cancer app during the first 6 months following diagnosis, in terms of
benefits for clinical practice and research purposes. METHODS: Between June 2013
and April 2014, breast cancer patients of all ages were invited shortly after
diagnosis to use a supportive breast cancer app, and were followed for 6 months.
Patients were asked to use the app at their own convenience. In-depth interviews
were conducted regularly with patients and their medical team (ie, physicians and
nurses) to evaluate their experiences. RESULTS: A total of 15 patients aged 30-63
years participated. The medical team consisted of 7 physicians and 3 specialized
breast cancer nurses. Out of the 15 patients, 12 (80%) used the app to obtain
information on breast cancer and treatment. A total of 11 out of 12 patients
(92%) evaluated this information as useful. All 15 patients used the app to
record consultations with practitioners, and 14 (93%) found this useful. Symptom
registration was used by 8 out of 15 patients (53%), and was found useful by 4
out of these 8 patients (50%). Overall, 14 out of 15 patients (93%) would
recommend the app to other patients. The app, in particular the recording
function, was rated as useful by 9 out of 10 medical professionals (90%), and
they reported that it did not increase consultation time. These 9 professionals
would recommend the app to their patients. CONCLUSIONS: This evaluation of a
supportive health app shows positive experiences among patients and their medical
teams. Based on experiences in this study, patients may need to be actively
encouraged to regularly register symptoms within health apps to generate
sufficient patient-reported app data for use in clinical practice and scientific
research.
PMID- 28410171
TI - An eHealth Intervention to Increase Physical Activity and Healthy Eating in Older
Adult Cancer Survivors: Summative Evaluation Results.
AB - BACKGROUND: A healthy lifestyle is associated with improved quality of life among
cancer survivors, yet adherence to health behavior recommendations is low.
OBJECTIVE: This pilot trial developed and tested the feasibility of a tailored
eHealth program to increase fruit and vegetable consumption and physical activity
among older, long-term cancer survivors. METHODS: American Cancer Society (ACS)
guidelines for cancer survivors were translated into an interactive, tailored
health behavior program on the basis of Social Cognitive Theory. Patients (N=86)
with a history of breast (n=83) or prostate cancer (n=3) and less than 5 years
from active treatment were randomized 1:1 to receive either provider advice,
brief counseling, and the eHealth program (intervention) or advice and counseling
alone (control). Primary outcomes were self-reported fruit and vegetable intake
and physical activity. RESULTS: About half (52.7%, 86/163) of the eligible
patients consented to participate. The most common refusal reasons were lack of
perceived time for the study (32/163) and lack of interest in changing health
behaviors (29/163). Furthermore, 72% (23/32) of the intervention group reported
using the program and most would recommend it to others (56%, 14/25). Qualitative
results indicated that the intervention was highly acceptable for survivors. For
behavioral outcomes, the intervention group reported increased fruit and
vegetable consumption. Self-reported physical activity declined in both groups.
CONCLUSIONS: The brief intervention showed promising results for increasing fruit
and vegetable intake. Results and participant feedback suggest that providing the
intervention in a mobile format with greater frequency of contact and more
indepth information would strengthen treatment effects.
PMID- 28410172
TI - Adolescent and Young Adult Cancer Survivorship Educational Programming: A
Qualitative Evaluation.
AB - BACKGROUND: This program evaluation considers the need for increased professional
and patient education for adolescent and young adult (AYA) cancer survivorship.
Due to the high incidence of late effects of cancer treatment among AYA cancer
survivors, knowledge sharing and communications are needed throughout the
transition from cancer care into community care. AYA survivors are likely to need
developmentally appropriate psychosocial care as well as extensive follow-on
surveillance by physicians who are educated and aware of the likely chronic
conditions and late effects that may occur in these patients. OBJECTIVE: The
objective of this study was to evaluate the outcomes of the After Cancer Care
Ends, Survivorship Starts for Adolescent and Young Adults (ACCESS AYA)
programming. The intent of the ACCESS AYA program was to build health literacy
around AYA survivorship issues and to stimulate improved communications between
survivors and health care providers. This paper addresses the central research
question of "How did the ACCESS AYA program increase health literacy,
communications, and understanding among AYA survivors and providers?" METHODS:
The primarily qualitative evaluation included a brief introductory survey of
participant awareness and effectiveness of the ACCESS AYA project serving as a
recruitment tool. Survey respondents were invited to participate in in-depth
interviews based on interview guides tailored to the different stakeholder
groups. The evaluation used the Atlas Ti qualitative database and software for
coding and key word analyses. Interrater reliability analyses were assessed using
Cohen kappa analysis with Stata 12.1 (StataCorp LLC) software. RESULTS: The key
themes, which included survivor wellbeing, health care professional education,
cancer advocates role and education, hospital and community-based resources, and
the role of societal support, are presented in a concept map. The interrater
reliability scores (ranging from 1 to minus 1) were .893 for first cycle coding
and .784 for the second cycle. In the brief quantitative survey based on a scale
of 1 to 5 with 5 as high, the 22 respondents rated their level of awareness of
the project with a mean 3.2 (CI 3.02-3.45) and project effectiveness with a mean
of 4 (CI 3.72-4.27). CONCLUSIONS: This study contributes to understanding of the
ACCESS AYA survivor community in central Texas and the health care professionals
and advocates who aid them in their efforts to a new normal life and wellbeing in
their survivorship. The results of the evaluation highlight the need to continue
to build both survivor and professional resources to address the unique impact of
cancer on AYA cancer survivors.
PMID- 28410173
TI - eHealth in Modern Patient-Caregiver Communication: High Rate of Acceptance Among
Physicians for Additional Support of Breast Cancer Patients During Long-Term
Therapy.
AB - BACKGROUND: Lack of adherence and compliance with drug regimens among breast
cancer patients represent substantial problems in oral therapies, leading to
significant impacts on mortality. Where other systems have failed, electronic
health (eHealth) could be a possible solution to improve medication intake, along
with the doctor-patient relationship. Initial results from studies concerning new
interventions for therapy support are promising, but reports suggest that general
acceptance of new treatment support tools is needed among patients and physicians
alike. OBJECTIVE: The aim of this study was to investigate the actual use of the
Internet and other modern media among physicians involved in breast cancer
treatment. METHODS: Using a standardized questionnaire, actual utilization of new
media among physicians was analyzed. Internet-related behaviors in private, as
well as in business life, were investigated. Attention was focused on physicians'
opinions regarding modern eHealth tools and how patients could be best supported
to enhance adherence. RESULTS: A total of 120 physicians, all participating in
breast cancer care, completed the questionnaire (median age 41 years). Almost all
participants (99.2%, 119/120) used the Internet for general purposes and 98.3%
(118/120) used it for medical issues as well. Virtually all medical professionals
(99.2%, 119/120) reported that they owned a computer, while more recently
invented technologies such as tablets and smartphones were owned by 31.9%
(38/119) and 73.1% (87/119), respectively. The Internet was favored by 66.4%
(79/119) of the physicians in our survey as a source for patient support; 71.2%
(84/118) would also favor modern media for side effect registration. Based on our
analysis, the most frequent Internet-utilizing physicians were characterized by
age <60, worked in a hospital, and were employed as a junior physician.
CONCLUSIONS: This study demonstrated a high usage of Internet-related
technologies among physicians, indicating that the use of eHealth for advanced
and individualized support in breast cancer care is a promising addition to
treatment management. Such technologies have the potential to enhance adherence
and compliance in therapy among cancer patients.
PMID- 28410174
TI - Pilot and Feasibility Test of a Mobile Health-Supported Behavioral Counseling
Intervention for Weight Management Among Breast Cancer Survivors.
AB - BACKGROUND: Health behavior and weight management interventions for cancer
survivors have the potential to prevent future cancer recurrence and improve long
term health; however, their translation can be limited if the intervention is
complex and involves high participant burden. Mobile health (mHealth) offers a
delivery modality to integrate interventions into daily life routines. OBJECTIVE:
The objective of this study was to evaluate the effects of a one-group trial with
a pre-post evaluation design on engagement (use and acceptability), physiological
(weight), behavioral (diet and physical activity), and other secondary outcomes.
METHODS: The 10-week intervention consisted of mHealth components (self
monitoring of selected diet behaviors via daily text messages, wireless devices
to automatically track weight and steps) and 4 motivational interviewing-based
technology-assisted phone sessions with a nonprofessionally trained counselor.
Participants were overweight breast cancer survivors who had completed treatment
and owned a smartphone. Weight was measured objectively; diet and physical
activity were measured with brief self-reported questionnaires. RESULTS: Ten
women participated; they had a mean age of 59 years (SD 6), 50% belonged to a
racial or ethnic minority group, 50% had some college or less, and 40% reported
using Medicaid health insurance. Engagement was high: out of 70 days in total,
the mean number of days recording steps via the wristband pedometer was 64 (SD
7), recording a weight via the scale was 45 (SD 24), and responding to text
messages was 60 (SD 13); 100% of participants completed all 4 calls with the
counselor. Most (90%) were very likely to participate again and recommend the
program to others. Mean weight in pounds decreased (182.5 to 179.1, mean change
3.38 [SD 7.67]), fruit and vegetable daily servings increased (2.89 to 4.42, mean
change 1.53 [SD 2.82]), and self-reported moderate physical activity increased in
metabolic equivalent of task (MET) minutes per week (2791 to 3336, mean change
545 [SD 1694]). CONCLUSIONS: Findings support the conduct of a fully powered
trial to evaluate the efficacy of mHealth as a feasible intervention modality for
breast cancer survivors. Future research should employ accelerometer-based
physical activity assessment and consider development of an all-in-one app to
integrate devices, messaging, and educational content and other mHealth
approaches to support behavioral counselors conducting weight management
interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02387671;
https://clinicaltrials.gov/ct2/show/NCT02387671 (Archived by WebCite at
http://www.webcitation.org/6hGEuttbZ).
PMID- 28410175
TI - Availability of Information About Lifestyle for Cancer Survivors in England: A
Review of Statutory and Charitable Sector Organizations and Cancer Centers.
AB - BACKGROUND: Health behavior change following a cancer diagnosis has the potential
to improve long-term outcomes. However, many patients do not receive professional
advice about lifestyle and are therefore increasingly using the Internet to seek
further information. The statutory and charitable sectors and cancer centers all
play an important role in the provision of information and have been found to be
favored by cancer survivors searching for information. However, to date there has
been no systematic evaluation of the lifestyle information available online for
cancer survivors. OBJECTIVE: The purpose of this review was to identify the
lifestyle information provided for cancer survivors by statutory and charitable
sector organizations and cancer centers in the United Kingdom. We aimed to
identify information on tobacco, physical activity, diet, weight, and alcohol
designed for people who have been diagnosed with breast, prostate, or colorectal
cancer. METHODS: The National Health Service (NHS) website was the focus of the
search for information provided by the statutory sector. Cancer centers were
identified from the Organization of European Cancer Institutes and an Internet
search, and charitable sector organizations were identified by searching the
Charity Commission database. The three largest generic, breast, prostate, and
colorectal cancer charitable organizations were included. A systematic search of
the organizations was conducted to identify lifestyle information for cancer
survivors. RESULTS: Ten organizations had some lifestyle information for cancer
survivors on their websites. The Christie NHS Foundation Trust, Macmillan Cancer
Support, and Prostate Cancer UK had the most comprehensive guides, covering
physical activity, diet, weight management, smoking, and alcohol. The NHS website
did not provide any information but had a link to Cancer Research UK's
information about diet. Eight organizations suggested talking to a health
professional before making any changes. CONCLUSIONS: The majority of
organizations included in this review would benefit from updating their websites
to include adequate information and advice about lifestyle for cancer survivors,
or they risk cancer survivors turning to less reliable sources of information.
Health professionals should be appropriately trained to deal with questions about
lifestyle and to advise cancer survivors about lifestyle changes following their
diagnosis.
PMID- 28410176
TI - Response Across the Health-Literacy Spectrum of Kidney Transplant Recipients to a
Sun-Protection Education Program Delivered on Tablet Computers: Randomized
Controlled Trial.
AB - BACKGROUND: Sun protection can reduce skin cancer development in kidney
transplant recipients, who have a greater risk of developing squamous cell
carcinoma than the general population. OBJECTIVE: A culturally sensitive sun
protection program (SunProtect) was created in English and Spanish with the
option of choosing audio narration provided by the tablet computer (Samsung
Galaxy Tab 2 10.1). The intervention, which showed skin cancer on patients with
various skin tones, explained the following scenarios: skin cancer risk, the
ability of sun protection to reduce this risk, as well as offered sun-protection
choices. The length of the intervention was limited to the time usually spent
waiting during a visit to the nephrologist. METHODS: The development of this
culturally sensitive, electronic, interactive sun-protection educational program,
SunProtect, was guided by the "transtheoretical model," which focuses on decision
making influenced by perceptions of personal risk or vulnerability to a health
threat, importance (severity) of the disease, and benefit of sun-protection
behavior. Transportation theory, which holds that narratives can have uniquely
persuasive effects in overcoming preconceived beliefs and cognitive biases
because people transported into a narrative world will alter their beliefs based
on information, claims, or events depicted, guided the use of testimonials.
Participant tablet use was self-directed. Self-reported responses to surveys were
entered into the database through the tablet. Usability was tested through
interviews. A randomized controlled pilot trial with 170 kidney transplant
recipients was conducted, where the educational program (SunProtect) was
delivered through a touch-screen tablet to 84 participants. RESULTS: The study
involved 62 non-Hispanic white, 60 non-Hispanic black, and 48 Hispanic/Latino
kidney transplant recipients. The demographic survey data showed no significant
mean differences between the intervention and control groups in age, sex, income,
or time since transplantation. The mean duration of program use varied by the
ethnic/racial group, with non-Hispanic whites having the shortest use (23
minutes) and Hispanic/Latinos having the longest use (42 minutes). Knowledge,
awareness of skin cancer risk, willingness to change sun protection, and use of
sun protection increased from baseline to 2 weeks after the program in
participants from all ethnic/racial groups in comparison with controls (P<.05).
Kidney transplant recipients with inadequate (47/170, 28%) and marginal
functional health literacy (59/170, 35%) listened to either Spanish or English
audio narration accompanying the text and graphics. After completion of the
program, Hispanic/Latino patients with initially inadequate health literacy
increased their knowledge more than non-Hispanic white and black patients with
adequate health literacy (P<.05). Sun protection implemented 2 weeks after
education varied by the ethnic/racial group. Outdoor activities were reduced by
Hispanics/Latinos, non-Hispanic blacks sought shade, Hispanic/Latinos and non
Hispanic blacks wore clothing, and non-Hispanic whites wore sunscreen (P<.05).
CONCLUSION: Educational program with a tablet computer during the kidney
transplant recipients' 6- or 12-month follow-up visits to the transplant
nephrologist improved sun protection in all racial/ethnic groups. Tablets may be
used to provide patient education and reduce the physician's burden of educating
and training patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01646099;
https://clinicaltrials.gov/ct2/show/NCT01646099.
PMID- 28410177
TI - Predictors of Online Cancer Prevention Information Seeking Among Patients and
Caregivers Across the Digital Divide: A Cross-Sectional, Correlational Study.
AB - BACKGROUND: The digital divide is a recognized public health problem caused by
social determinants that exacerbate health disparities. Despite the "tectonic
shift" in how most of the public obtains cancer information, underserved
communities are at increased risk of being digitally marginalized. However,
research that examines factors underlying eHealth information seeking in diverse
health contexts is lacking. OBJECTIVE: The aim of this paper is to explore
preferences and use of eHealth cancer prevention information (CPI) among patients
and caregivers attending a minority-serving oncology clinic using the
comprehensive model of information seeking as a theoretical framework.
Specifically, the study examined the role of social determinants and prevention
orientation in differences in preference and use of the Internet for CPI seeking
among this diverse sample. METHODS: Survey methodology was used to identify
social determinants and behavioral factors, including prevention orientation as
correlates and predictors of respondents' (n=252) preferences and use of eHealth
for CPI seeking. RESULTS: Less than half (112/252, 44.4%) of respondents said
that if faced with the need to seek CPI, they would seek this information online.
In the final logistic regression model, education, ethnicity, age, and prevention
orientation made significant contributions to the model (P<.05). Specifically,
for each year increase in age, participants were 3% less likely to use the
Internet for CPI seeking (P=.011). Compared to college graduates, respondents who
did not complete high school were 11.75 times less likely to cite the Internet as
a CPI carrier (P<.001) and those with a high school education were 3 times (2.99,
P=.015) less likely. In addition, the odds that a Spanish speaker would cite the
Internet as a CPI carrier were one-fifth (22%) of non-Hispanic whites (P=.032)
and about one-quarter (26%) of English-speaking Latinos (P=.036). Finally, with
each one point increase on the prevention orientation scale, respondents were
1.83 times less likely to cite online CPI seeking (P=.05). CONCLUSIONS: Social
determinants to health have profound influence on eHealth CPI seeking. Providers
and policy makers should focus on meeting patients and family members' CPI needs
following diagnosis and increase eHealth accessibility and availability of
evidence-based CPI to diverse populations. Future research is needed to unravel
further differences in eHealth CPI seeking, including those among Native
Americans that emerged as an additional digitally underserved racial/ethnic
group. Finally, additional factors underlying these differences should be
explored to better tailor CPI eHealth information to diverse communities'
information needs.
PMID- 28410178
TI - eHealth for Breast Cancer Survivors: Use, Feasibility and Impact of an
Interactive Portal.
AB - BACKGROUND: MijnAVL is an interactive portal including patient education,
overview of appointments, access to the electronic medical records (EMR), patient
reported outcomes, plus feedback and physical activity support. OBJECTIVE: With
this study we aimed to evaluate the use, feasibility, and impact of MijnAVL among
breast cancer survivors. METHODS: We included survivors currently or recently
treated with curative intent, who completed questions on sociodemographics,
patient activation (PAM), quality of life (SF-36), and physical activity (IPAQ).
MijnAVL could be used noncommittally for four months. Log data were collected
retrospectively and participants completed questions on acceptability,
satisfaction, and the PAM, SF-36 and IPAQ. RESULTS: Ninety-two women (mean age
49.5 years, 59% on-treatment) participated, with a mean number of logins of 8.7.
Overview of appointments (80% of participants) and access to the EMR (90%) were
most frequently used and most highly valued. Average website user satisfaction
was 3.8 on a 5-point scale. Although participants reported having more knowledge
and experiencing more control of their situation after using MijnAVL, PAM scores
did not change significantly. Three domains of the SF-36 (role functioning -
emotional, mental health, and social functioning) and median vigorous physical
activity improved significantly over time. The burden of MijnAVL for
professionals was limited. CONCLUSIONS: User experiences were positive and
exposure to MijnAVL was accompanied by improvements in three quality of life
domains and vigorous physical activity. Tailored features may be needed to
enhance the usefulness and efficacy of MijnAVL. Research with a controlled design
is needed to confirm our findings.
PMID- 28410179
TI - Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations
from the Clinical Trials Transformation Initiative Investigational New Drug
Safety Advancement Project.
AB - BACKGROUND: Use of electronic clinical trial portals has increased in recent
years to assist with sponsor-investigator communication, safety reporting, and
clinical trial management. Electronic portals can help reduce time and costs
associated with processing paperwork and add security measures; however, there is
a lack of information on clinical trial investigative staff's perceived
challenges and benefits of using portals. OBJECTIVE: The Clinical Trials
Transformation Initiative (CTTI) sought to (1) identify challenges to
investigator receipt and management of investigational new drug (IND) safety
reports at oncologic investigative sites and coordinating centers and (2)
facilitate adoption of best practices for communicating and managing IND safety
reports using electronic portals. METHODS: CTTI, a public-private partnership to
improve the conduct of clinical trials, distributed surveys and conducted
interviews in an opinion-gathering effort to record investigator and research
staff views on electronic portals in the context of the new safety reporting
requirements described in the US Food and Drug Administration's final rule (Code
of Federal Regulations Title 21 Section 312). The project focused on receipt,
management, and review of safety reports as opposed to the reporting of adverse
events. RESULTS: The top challenge investigators and staff identified in using
individual sponsor portals was remembering several complex individual passwords
to access each site. Also, certain tasks are time-consuming (eg, downloading
reports) due to slow sites or difficulties associated with particular operating
systems or software. To improve user experiences, respondents suggested that
portals function independently of browsers and operating systems, have intuitive
interfaces with easy navigation, and incorporate additional features that would
allow users to filter, search, and batch safety reports. CONCLUSIONS: Results
indicate that an ideal system for sharing expedited IND safety information is
through a central portal used by all sponsors. Until this is feasible, electronic
reporting portals should at least have consistent functionality. CTTI has issued
recommendations to improve the quality and use of electronic portals.
PMID- 28410180
TI - Rotterdam Prostate Cancer Risk Calculator: Development and Usability Testing of
the Mobile Phone App.
AB - BACKGROUND: The use of prostate cancer screening tools that take into account
relevant prebiopsy information (ie, risk calculators) is recommended as a way of
determining the risk of cancer and the subsequent need for a prostate biopsy.
This has the potential to limit prostate cancer overdiagnosis and subsequent
overtreatment. mHealth apps are gaining traction in urological practice and are
used by both practitioners and patients for a variety of purposes. OBJECTIVE: The
impetus of the study was to design, develop, and assess a smartphone app for
prostate cancer screening, based on the Rotterdam Prostate Cancer Risk Calculator
(RPCRC). METHODS: The results of the Rotterdam arm of the European Randomized
Study of Screening for Prostate Cancer (ERSPC) study were used to elaborate
several algorithms that allowed the risk of prostate cancer to be estimated. A
step-by-step workflow was established to ensure that depending on the available
clinical information the most complete risk model of the RPCRC was used. The user
interface was designed and then the app was developed as a native app for iOS.
The usability of the app was assessed using the Post-Study System Usability
Questionnaire (PSSUQ) developed by IBM, in a group of 92 participants comprising
urologists, general practitioners, and medical students. RESULTS: A total of 11
questions were built into the app, and, depending on the answers, one of the
different algorithms of the RPCRC could be used to predict the risk of prostate
cancer and of clinically significant prostate cancer (Gleason score >=7 and
clinical stage >T2b). The system usefulness, information quality, and interface
quality scores were high-92% (27.7/30), 87% (26.2/30), and 89% (13.4/15),
respectively. No usability problems were identified. CONCLUSIONS: The RPCRC app
is helpful in predicting the risk of prostate cancer and, even more importantly,
clinically significant prostate cancer. Its algorithms have been externally
validated before and the usability score shows the app's interface is well
designed. Further usability testing is required in different populations to
verify these results and ensure that it is easy to use, to warrant a broad
appeal, and to provide better patient care.
PMID- 28410181
TI - Alcohol Intake Among Breast Cancer Survivors: Change in Alcohol Use During a
Weight Management Intervention.
AB - BACKGROUND: Daily alcohol intake in quantities as small as half a drink/day
significantly increases the risk of breast cancer recurrence for postmenopausal
survivors. Interventions designed to modify alcohol use among survivors have not
been studied; however, lifestyle interventions that target change in dietary
intake may affect alcohol intake. OBJECTIVE: To evaluate change in alcohol use
during a weight loss intervention for obese, rural-dwelling breast cancer
survivors. METHODS: Data were derived from an 18-month trial that included a 6
month weight loss intervention delivered via group conference calls, followed by
a 12-month randomized weight loss maintenance phase in which participants
received continued group calls or mailed newsletters. Participants who reported
regular alcohol use at baseline (N=37) were included in this study. RESULTS: Mean
daily alcohol intake significantly decreased from baseline to 6 months during the
weight loss intervention (19.6-2.3 g; P=.001). Mean alcohol intake did not
significantly increase (b=0.99, P=.12) during the weight loss maintenance phase
(months 6-18) and did not depend on randomization group (b=0.32, P=.799).
CONCLUSIONS: Findings provide preliminary evidence that a weight loss
intervention may address obesity and alcohol use risk factors for cancer
recurrence. Minimal mail-based contact post weight loss can maintain alcohol use
reductions through 18 months, suggesting durability in these effects. These
results highlight a possibility that lifestyle interventions for survivors may
modify health behaviors that are not the main foci of an intervention but that
coincide with intervention goals. TRIAL REGISTRATION: Clinicaltrials.gov
NCT01441011; https://clinicaltrials.gov/ct2/show/NCT01441011 (Archived by WebCite
at http://www.webcitation.org/6lsJ9dMa9).
PMID- 28410182
TI - Parent and Health Care Provider Perceptions for Development of a Web-Based Weight
Management Program for Survivors of Pediatric Acute Lymphoblastic Leukemia: A
Mixed Methods Study.
AB - BACKGROUND: Survivors of pediatric acute lymphoblastic leukemia (ALL) may
experience unhealthy weight gain during treatment, which has been associated with
higher risk for chronic health issues. OBJECTIVE: The purpose of this study was
to obtain feedback on weight management in pediatric ALL survivors and on the
content and implementation of a Web-based weight management program. METHODS:
Study participants included 54 parent survey respondents and 19 pediatric
oncology professionals in 4 focus groups. Survey questions included report of
child weight status and interest in participating in weight management
programming at various time points. Pediatric oncology professionals were asked
about the preferred topics and timing, as well as their role. Focus group data
were analyzed by a multidisciplinary research team for common themes. RESULTS:
The mean age of survivors was 6.5 years. By parent report, 19% of children were
overweight and 25% were obese. Preferred timing for weight management program
participation was within 3 months of starting maintenance chemotherapy (23/53,
43%) or within 12 months after completion of all cancer treatments (18/53, 34%).
Pediatric oncology professionals likewise considered the maintenance phase
appropriate. They considered parenting to be an important topic to include and
indicated that their most appropriate roles would be promotion and support.
CONCLUSIONS: Parents and pediatric oncology professionals are interested in and
supportive of early weight management in pediatric ALL survivors. Future research
needs to identify strategies to integrate this into pediatric cancer care and to
evaluate the feasibility and efficacy of these strategies.
PMID- 28410183
TI - Online Versus Telephone Methods to Recruit and Interview Older Gay and Bisexual
Men Treated for Prostate Cancer: Findings from the Restore Study.
AB - BACKGROUND: Recently, researchers have faced the challenge of conflicting
recommendations for online versus traditional methods to recruit and interview
older, sexual minority men. Older populations represent the cohort least likely
to be online, necessitating the use of traditional research methods, such as
telephone or in-person interviews. By contrast, gay and bisexual men represent a
population of early adopters of new technology, both in general and for medical
research. In a study of older gay and bisexual men with prostate cancer, we asked
whether respondents preferred online versus offline methods for data collection.
Given the paucity of research on how to recruit older gay and bisexual men in
general, and older gay and bisexual men with prostate cancer in particular, we
conducted an observational study to identify participant preferences when
participating in research studies. OBJECTIVE: To test online versus offline
recruitment demographic data collection, and interview preferences of older gay
and bisexual men with prostate cancer. METHODS: Email blasts were sent from a
website providing support services for gay and bisexual men with prostate cancer,
supplemented with an email invitation from the web-host. All invitations provided
information via the study website address and a toll-free telephone number. Study
tasks included respondents being screened, giving informed consent, completing a
short survey collecting demographic data, and a 60-75 minute telephone or
Internet chat interview. All materials stressed that enrollees could participate
in each task using either online methods or by telephone, whichever they
preferred. RESULTS: A total of 74 men were screened into the study, and 30 were
interviewed. The average age of the participants was 63 years (standard deviation
6.9, range 48-75 years), with most residing in 14 American states, and one
temporarily located overseas. For screening, consent, and the collection of
demographic data, 97% (29/30) of the participants completed these tasks using
online methods. For the interview, 97% (29/30) chose to be interviewed by
telephone, rather than Internet chat. CONCLUSIONS: Older gay and bisexual men,
when given choices, appear to prefer a mixed methods approach to qualitative
investigations. For most aspects of the study, the older men chose online
methods; the exception was the interview, in which case almost all preferred
telephone. We speculate that a combination of the deeply personal nature of the
topic (sexual effects of prostate cancer treatment), unfamiliarity with online
chat, and possibly the subject burden involved in extensive typing contributed to
the preference of telephone versus online chat. Recruitment of older men into
this study showed good geographic diversity. We recommend that other qualitative
researchers consider a mixed methods approach when recruiting older populations
online.
PMID- 28410184
TI - The Effects of Physical Activity on Health and Quality of Life in Adolescent
Cancer Survivors: A Systematic Review.
AB - BACKGROUND: There are numerous published controlled trials assessing the safety
and the benefits of physical activity (PA) for child and adult cancer survivors.
However, trials exclusively comprised of adolescent cancer survivors aged 13-19
years, who may experience different health and quality of life (QOL) effects as a
function of their developmental status, are lacking. Rather, some trials have
included both adolescent and child cancer survivors together. OBJECTIVE: The aim
of this systematic review was to synthesize the findings from randomized
controlled trails (RCTs) and controlled clinical trials (CCTs) investigating the
effects of PA on health and QOL outcomes in samples comprised of >50% adolescent
cancer survivors to summarize the current state of evidence, identify knowledge
gaps, and highlight areas in need of additional research within this population.
METHODS: Using a search strategy developed for this review, 10 electronic
databases were searched for RCTs and CCTs that reported on the effects of PA on
at least 1 health and/or QOL outcome in samples comprised of >50% adolescent
cancer survivors. RESULTS: From the 2249 articles identified, 2 CCTs met the
predetermined eligibility criteria and were included in this review. Combined, 28
adolescents (of 41 participants) who were receiving active treatment participated
in the 2 studies reviewed. A total of 4 health and QOL outcomes (ie, bone mass,
fatigue, grip strength, QOL) were assessed pre- and post-PA intervention.
CONCLUSIONS: On the basis of the 2 studies reviewed, PA appears to be safe and
feasible. PA also shows promise to mitigate reductions in bone mass and might be
a viable strategy to improve fatigue, grip strength, and QOL. High-quality
controlled trials with larger samples exclusively comprised of adolescent cancer
survivors that assess a wide range of outcomes are needed to determine the
effects of PA on health and QOL outcomes in this population.
PMID- 28410185
TI - "Googling" for Cancer: An Infodemiological Assessment of Online Search Interests
in Australia, Canada, New Zealand, the United Kingdom, and the United States.
AB - BACKGROUND: The infodemiological analysis of queries from search engines to shed
light on the status of various noncommunicable diseases has gained increasing
popularity in recent years. OBJECTIVE: The aim of the study was to determine the
international perspective on the distribution of information seeking in Google
regarding "cancer" in major English-speaking countries. METHODS: We used Google
Trends service to assess people's interest in searching about "Cancer" classified
as "Disease," from January 2004 to December 2015 in Australia, Canada, New
Zealand, the United Kingdom, and the United States. Then, we evaluated top cities
and their relative search volumes (SVs) and country-specific "Top searches" and
"Rising searches." We also evaluated the cross-country correlations of SVs for
cancer, as well as rank correlations of SVs from 2010 to 2014 with the incidence
of cancer in 2012 in the abovementioned countries. RESULTS: From 2004 to 2015,
the United States (relative SV [from 100]: 63), Canada (62), and Australia (61)
were the top countries searching for cancer in Google, followed by New Zealand
(54) and the United Kingdom (48). There was a consistent seasonality pattern in
searching for cancer in the United States, Canada, Australia, and New Zealand.
Baltimore (United States), St John's (Canada), Sydney (Australia), Otaika (New
Zealand), and Saint Albans (United Kingdom) had the highest search interest in
their corresponding countries. "Breast cancer" was the cancer entity that
consistently appeared high in the list of top searches in all 5 countries. The
"Rising searches" were "pancreatic cancer" in Canada and "ovarian cancer" in New
Zealand. Cross-correlation of SVs was strong between the United States, Canada,
and Australia (>.70, P<.01). CONCLUSIONS: Cancer maintained its popularity as a
search term for people in the United States, Canada, and Australia, comparably
higher than New Zealand and the United Kingdom. The increased interest in
searching for keywords related to cancer shows the possible effectiveness of
awareness campaigns in increasing societal demand for health information on the
Web, to be met in community-wide communication or awareness interventions.
PMID- 28410186
TI - Online Social Engagement by Cancer Patients: A Clinic-Based Patient Survey.
AB - BACKGROUND: The Internet is commonly used as a source of health information, but
little is known about the Internet practices specific to cancer patients.
OBJECTIVE: To understand cancer patients' use of the Internet as an informational
resource and for social support. METHODS: The researchers conducted a survey of
1282 patients at a comprehensive cancer center to assess frequency of Internet
access and online behaviors. RESULTS: Of the cancer patients surveyed, 1096
(85.49%) had Internet access; of those with Internet access, 953 (86.95%)
reported going online at least weekly, and 747 (68.16%) reported daily online
activity. Grouping Internet users by their level of online social engagement
revealed that out of 1096 users, 331 (30.20%) had not sought out social
connections online, 227 (20.71%) had read about experiences from other cancer
patients, 410 (37.41%) had also written about their personal experiences, and 128
(11.68%) had participated in a formal online group for cancer patients. Increased
online social engagement was associated with an increased perception that the
Internet was useful for social support. CONCLUSIONS: Internet use among cancer
patients was common, and most patients reported that they found useful
information about their cancer diagnosis online. Cancer patients who actively
posted or shared content perceived more social support from the Internet than
those who used the Internet solely as an informational resource or to read about
other cancer patients' experiences. Physicians have a great opportunity to direct
users to quality health information on the Web.
PMID- 28410187
TI - Comparing Web-Based Provider-Initiated and Patient-Initiated Survivorship Care
Planning for Cancer Patients: A Randomized Controlled Trial.
AB - BACKGROUND: Survivorship care plans (SCPs) are intended to facilitate
communication and coordination between patients, oncologists, and primary care
providers. Most SCP initiatives have focused on oncology providers initiating the
SCP process, but time and resource barriers have limited uptake. OBJECTIVE: This
trial compares the feasibility and value of 2 Web-based SCP tools: provider
initiated versus patient-initiated. METHODS: This mixed-methods study recruited
clinicians from 2 academically-affiliated community oncology practices. Eligible
patients were treated by a participating oncologist, had nonmetastatic cancer,
completed acute treatment <= 2 months before enrollment, and had no evidence of
disease. Patients were randomized 1:1 to either provider-initiated or patient
initiated SCPs-both are Web-based tools. We conducted qualitative interviews with
providers at baseline and follow-up and with patients 2 months after enrollment.
In addition, patients were administered the Preparing for Life as a (New)
Survivor (PLANS) and Cancer Survivors' Unmet Needs (CaSUN) surveys at baseline
and 2 months. RESULTS: A total of 40 providers were approached for the study, of
whom 13 (33%) enrolled. Providers or clinic staff required researcher assistance
to identify eligible patients; 41 patients were randomized, of whom 25 completed
follow-up (61%; 13 provider-initiated, 12 patient-initiated). Of the 25, 11 (44%)
had initiated the SCP; 5 (20%) provided the SCP to their primary care provider.
On the Preparing for Life as a (New) Survivor and Cancer Survivors' Unmet Needs,
patients in both arms tended to report high knowledge and confidence and few
unmet needs. In qualitative interviews, providers and patients discussed SCPs'
value. CONCLUSIONS: Regardless of patient- versus provider-initiated templates
and the Web-based design of these tools, barriers to survivorship care planning
persist. Further efforts should emphasize workflow functions for identifying and
completing SCPs-regardless of the SCP form used. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02405819; https://clinicaltrials.gov/ct2/show/NCT02405819
(Archived by WebCite at http://www.webcitation.org/6jWqcWOvK).
PMID- 28410188
TI - Like or Dislike? Impact of Facebook on Ewing Sarcoma Treatment.
AB - BACKGROUND: An increasing number of patients are raising their voices in online
forums to exchange health-related information. Facebook is the leading social
media platform with more than 1 billion international daily users recorded in the
summer of 2015. Facebook has a dynamic audience and is utilized in a number of
ways, discussing medical issues being one of them. Ewing sarcoma mainly affects
teenagers and young adults. Additionally, many individuals within this age group
are regular users of Facebook. However, little is known about the impact of this
modern way of communication via Web-based platforms on patients with Ewing
sarcoma and their social environment. OBJECTIVE: The aim of this study was to
analyze and compare Ewing sarcoma patients' and relatives' behavior on Facebook
to draw conclusions regarding the impact of Facebook on Ewing sarcoma treatment.
METHODS: We examined a Facebook group named "Ewing Sarcoma Awareness" that is
used to exchange information for both patients and relatives regarding Ewing
sarcoma. A self-designed questionnaire was used to compare patients' and
relatives' answers. Additionally, we analyzed all processes (posts, likes,
threads, links) in the group for 6 consecutive months. A total of 65 members of
the Facebook group (26 patients, 39 relatives) out of 2227 international group
members participated in our study. RESULTS: More than 70% (46/65) of all
participants reported that they use the group Ewing Sarcoma Awareness as a source
of information about Ewing sarcoma. Of the participants, 89% (58/65) agreed on
our scale from a little to a lot that being in contact with other affected people
through the group makes it easier to handle the diagnosis. In this study, 20%
(13/65) of all participants reported that the group affected their choice of
treatment and 15% (10/65) of participants were influenced in the selection of
their specialist. Regarding the recommendation of the Facebook group toward other
people, significant differences (P=.003) were found comparing patients' and
relatives' results. During the last 6 months most activities in the group
concerned sharing destiny and handling the diagnosis. CONCLUSIONS: The Facebook
group Ewing Sarcoma Awareness has a relevant impact on group members regarding
their choice of treatment. Moreover, participants turn toward the group to
receive mental and emotional support in everyday life. Statements made within the
group are in part questionable from a medical point of view and the impact made
by these statements on patients' care requires further evaluation.
PMID- 28410189
TI - EHealth Acceptance and New Media Preferences for Therapy Assistance Among Breast
Cancer Patients.
AB - BACKGROUND: Electronic health (eHealth) and mobile communication-based health
care (mHealth) applications have been increasingly utilized in medicine over the
last decade, and have facilitated improved adherence to therapy regimens in
patients with chronic conditions. Due to the long duration of breast cancer
therapy, and the long course of disease in metastatic breast cancer, a need for
more intensified physician-patient communication has emerged. Various support
mechanisms, including new media such as mHealth and eHealth, have been proposed
for this purpose. OBJECTIVE: The aim of this study was to analyze the correlation
between sociodemographic factors, as well as health status of breast cancer
patients, and their current utilization of new media, or their willingness to use
Internet and mobile phone apps for improvement of therapy management. METHODS:
The survey for this study was conducted anonymously during the 2012 Mamazone
Projekt Diplompatient meeting (Augsburg, Germany), which hosted approximately 375
participants per day. A total of 168 questionnaires were completed. The
questionnaire aimed to assess sociodemographic status, disease patterns, and
current use of new media (ie, Internet, mobile phone, and mobile phone apps) in
breast cancer patients. Habits and frequency of use for these new technologies,
as well as patients' affinity towards eHealth and mHealth tools for therapy
management improvement, were investigated. RESULTS: Almost all participants used
the Internet (95.8%, 161/168), with 91.5% (151/165) also utilizing this
technology for health-related issues. Approximately 23% (38/168) of respondents
owned a mobile phone. When asked about their preferences for therapy assistance,
67.3% (113/168) of respondents were interested in assistance via the Internet,
25.0% (42/168) via mobile phone, and 73.2% (123/168) via call center. Patients
diagnosed with breast cancer <5 years before the survey were significantly more
interested in a call center than patients diagnosed >5 years before survey
participation. CONCLUSIONS: The vast majority of breast cancer patients accept
the Internet for therapy assistance, which indicates that eHealth is a promising
medium to improve patient-physician communication. Such technologies may improve
individual disease management and ultimately lead to an enhanced adherence to
therapy regimens.
PMID- 28410190
TI - Dietary oleuropein inhibits tumor angiogenesis and lymphangiogenesis in the
B16F10 melanoma allograft model: a mechanism for the suppression of high-fat diet
induced solid tumor growth and lymph node metastasis.
AB - Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates
melanoma progression in the B16F10 allograft model. In this study, we examined
whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits
HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD
diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were
subcutaneously injected and the primary tumor was resected 3 weeks later. OL
suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD
induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2),
lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1alpha
and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2
macrophages (MPhis). All animals were euthanized 2.5 weeks after tumor resection.
OL suppressed HFD-induced increases in lymph node (LN) metastasis; expression of
VEGF-A, VEGF-C, and VEGF-D in the LN; and M2-MPhis and the size of adipocytes in
adipose tissues surrounding LNs. Co-culture results revealed that the crosstalk
between B16F10s, M2-MPhis, and differentiated 3T3-L1 cells under hypoxic
conditions increased the secretion of VEGF-A and -D, which stimulated tube
formation and migration of endothelial cells (HUVECs) and lymphatic endothelial
cells (LEC), respectively. Additionally, OL directly inhibited the
differentiation of 3T3-L1 preadipocytes and tube formation by HUVECs and LECs.
The overall results indicated that dietary OL inhibits lipid and M2-MPhi
accumulation in HFD-fed mice, which contributes to decreases in VEGF secretion,
thereby leading to inhibition of angiogenesis and lymphangiogenesis.
PMID- 28410191
TI - Loss of PTEN expression in breast cancer: association with clinicopathological
characteristics and prognosis.
AB - Various studies have evaluated the significance of PTEN (phosphatase and tensin
homolog deleted from chromosome 10) expression in breast cancer, but their
results remain controversial. We conducted a meta-analysis to evaluate the
associations of PTEN expression with clinicopathological characteristics and
prognosis in breast cancer. PubMed, Embase, Web of Science, and China National
Knowledge Infrastructure were searched to identify relevant publications. The
associations between PTEN expression and clinicopathological parameters, disease
free survival (DFS), and overall survival (OS) were then assessed via meta
analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals
(CIs). Based on 27 studies involving 10,231 patients, the pooled results revealed
that PTEN loss was significantly more common in breast cancer than in normal
tissues (OR = 12.15, 95% CI = 6.48-22.79, P < 0.00001) and that PTEN loss had
clear associations with larger tumor size (> 2 cm, OR = 0.62, 95% CI = 0.48-0.82,
P = 0.0006), lymph node metastasis(OR = 0.61, 95% CI = 0.45-0.82, P = 0.0001),
later TNM stage(stage III-IV, OR = 0.55, 95% CI = 0.35-0.86, P = 0.009), poor
differentiation(OR = 0.37, 95% CI = 0.24-0.59, P < 0.0001), and the highly
aggressive triple-negative phenotype (OR = 1.62, 95% CI = 1.23-2.12, P = 0.0005).
Moreover, patients with PTEN loss exhibited significantly worse DFS and OS(HR =
1.63, 95% CI = 1.04-2.22, P < 0.00001; HR = 1.41, 95% CI = 1.08-1.73, P < 0.0001;
respectively). In conclusion, PTEN loss might predict more aggressive behavior
and worse outcomes in patients with breast cancer.
PMID- 28410192
TI - Pellino 1 inactivates mitotic spindle checkpoint by targeting BubR1 for
ubiquitinational degradation.
AB - Aberrant constitutive activation of receptor-mediated downstream signalling plays
an active role in the deregulation of cell cycle control. The mitotic spindle
checkpoint is important in preventing abnormal mitotic cell cycle with chromosome
missegregation from achieving neoplastic aneuploidy. However, mechanisms coupling
receptor-mediated signalling to mitotic spindle checkpoint regulation remain
unclear. Pellino 1 is a receptor signal-responsive E3 ubiquitin ligase, and the
application of certain receptor-mediated signalling regulates the expression and
activity of Pellino 1. In the present study, Pellino 1 expression induced
extensive chromosome aneuploidy and allowed abnormal mitotic cells to adapt and
become aneuploid in vitro and in vivo. Pellino 1 directly interacted with BubR1,
a key component of mitotic spindle checkpoint, in a mitotic cell-cycle dependent
manner, and down-regulated the stability of BubR1 by ubiquitination-mediated
degradation and induced mitotic dysfunction. In summary, Pellino 1 expression
acts as an inhibitory signal of the homeostatic regulation of mitotic cell cycle
and checkpoint, and thus contributes to the initiation and progression of
neoplastic chromosome aneuploidy.
PMID- 28410193
TI - Metabolic targeting of EGFRvIII/PDK1 axis in temozolomide resistant glioblastoma.
AB - Glioblastomas are characterized by amplification of EGFR. Approximately half of
tumors with EGFR over-expression also express a constitutively active ligand
independent EGFR variant III (EGFRvIII). While current treatments emphasize
surgery followed by radiation and chemotherapy with Temozolomide (TMZ), acquired
chemoresistance is a universal feature of recurrent GBMs. To mimic the GBM
resistant state, we generated an in vitro TMZ resistant model and demonstrated
that dichloroacetate (DCA), a metabolic inhibitor of pyruvate dehydrogenase
kinase 1 (PDK1), reverses the Warburg effect. Microarray analysis conducted on
the TMZ resistant cells with their subsequent treatment with DCA revealed PDK1 as
its sole target. DCA treatment also induced mitochondrial membrane potential
change and apoptosis as evidenced by JC-1 staining and electron microscopic
studies. Computational homology modeling and docking studies confirmed DCA
binding to EGFR, EGFRvIII and PDK1 with high affinity. In addition, expression of
EGFRvIII was comparable to PDK1 when compared to EGFR in GBM surgical specimens
supporting our in silico prediction data. Collectively our current study provides
the first in vitro proof of concept that DCA reverses the Warburg effect in the
setting of EGFRvIII positivity and TMZ resistance leading to GBM cytotoxicity,
implicating cellular tyrosine kinase signaling in cancer cell metabolism.
PMID- 28410194
TI - Chicoric acid is a potent anti-atherosclerotic ingredient by anti-oxidant action
and anti-inflammation capacity.
AB - Atherosclerotic cardiovascular disease is linked to both oxidative stress and
endothelial cell dysfunction. Chicoric acid has antioxidant and anti-inflammatory
properties. In the present investigation, we demonstrated that chicoric acid
inhibits oxidized low-density lipoprotein (oxLDL)-facilitated dysfunction in
human umbilical vein endothelial cells (HUVECs). Oxidative injuries were tested
by investigating the formation of intracellular reactive oxygen species (ROS) and
by examining the activity of antioxidant enzymes and the function of endothelial
nitric oxide synthase (eNOS). We also confirmed that chicoric acid mitigates
apoptotic features caused by oxLDL, such as the subsequent break down of
mitochondrial transmembrane potential and the activation of Bax, which promote
DNA strand breaks and activate caspase-3. Moreover, our data revealed that
chicoric acid attenuated the oxLDL activation of NF-kappaB, the attachment of THP
1 cells and the overexpression of adhesion molecules in human endothelial cells.
The results of this study suggest a potential molecular mechanism through which
chicoric acid inhibits oxLDL-induced human endothelial dysfunction.
PMID- 28410195
TI - Antagonistic effects of selenium on lead-induced autophagy by influencing
mitochondrial dynamics in the spleen of chickens.
AB - Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has
antagonistic effects on Pb. In our study, brown layer chickens were randomly
allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and
350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the
90th day; spleen tissues were subjected to observation of ultrastructure and
detection of spleen-related indexes. The results revealed that in the Pb group,
expression levels of the cytokines IL-1 and TNF-alpha significantly increased,
and expression levels of IL-2 and INF-gamma significantly decreased; activities
of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression
level of malondialdehyde (MDA) significantly increased; expression levels of
mitochondrial fission-related genes (Mff and Drp1) significantly increased, and
expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2)
significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein,
Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of
rapamycin (mTOR) was downregulated. The results of transmission electron
microscopy indicated that Pb induced mitochondrial fragmentation, and triggered
autophagy in the spleen of chickens. The Se and Pb co-treatment remarkably
alleviated these injuries induced by Pb in the spleen of chickens. In conclusion,
Pb can induce the oxidative stress to influence the mitochondrial dynamics
balance and lead to autophagy, which triggers the immune dysfunction in the
spleen of chickens; the Se exhibits the antagonistic effects on lead-induced
autophagy by influencing mitochondrial dynamics in the spleen of chickens.
PMID- 28410196
TI - The p38 signaling pathway mediates quiescence of glioma stem cells by regulating
epidermal growth factor receptor trafficking.
AB - EGFR pathway is upregulated in malignant gliomas, and its downstream signaling is
important for self-renewal of glioma cancer stem-like cells (GSC). p38 mitogen
activated protein kinase (MAPK) signaling, a stress-activated signaling cascade
with suppressive and permissive effects on tumorigenesis, can promote
internalization and ubiquitin ligase mediated degradation of EGFR. In this study,
we investigated the role of p38 MAPK signaling on the self-renewal of GSCs with
the hypothesis that inhibition may lead to enhanced self-renewal capacity by
retention of EGFR. Inhibition of p38 MAPK pathway led to increase in EGFR
expression but surprisingly, reduced proliferation. Additional functional
evaluation revealed that p38 inhibition was associated with decrease in cell
death and maintenance of undifferentiated state. Further probing the effect of
p38 inhibition demonstrated attenuation of EGFR downstream signaling activity in
spite of prolonged surface expression of the receptor. In vitro observations were
confirmed in xenograft in vivo experiments. These data suggest that p38 MAPK
control of EGFR signaling activity may alter GSC cell cycle state by regulating
quiescence and passage into transit amplifying state.
PMID- 28410197
TI - Associations of the glutathione S-transferase P1 Ile105Val genetic polymorphism
with gynecological cancer susceptibility: a meta-analysis.
AB - : The association between the glutathione S-transferase P1 (GSTP1) Ile105Val
polymorphism and gynecological cancer susceptibility has been evaluated in many
studies. However, the results remain controversial. Thus, this meta-analysis,
based on 10 published case-control studies, was designed to clarify the
association of the GSTP1 Ile105Val polymorphism with gynecological cancer risk.
Our results suggested that there was no significant association between the GSTP1
Ile105Val polymorphism and the risk of gynecological cancer in all genetic models
(GG vs. AA: odds ratio [OR] = 1.41, 95% confidence interval [CI] = 0.75-2.26; AG
vs. AA: OR = 1.13, 95% CI = 0.74-1.73; AG/GG vs. AA: OR = 1.17, 95% CI = 0.75
1.81; GG vs. AA/AG: OR = 1.38, 95% CI = 0.79-2.42). Similarly, in the subgroup
analyses by cancer type, ethnicity, and smoking status, no significant
association with any genetic model was observed. In conclusion, the results of
our meta-analysis suggest that the GSTP1 Ile105Val polymorphism is not associated
with the development of gynecological cancer.
PMID- 28410198
TI - Specific changes in mitochondrial lipidome alter mitochondrial proteome and
increase the geroprotective efficiency of lithocholic acid in chronologically
aging yeast.
AB - We have previously found that exogenously added lithocholic acid delays yeast
chronological aging. We demonstrated that lithocholic acid enters the yeast cell,
is sorted to mitochondria, resides in both mitochondrial membranes, changes the
relative concentrations of different membrane phospholipids, triggers changes in
the concentrations of many mitochondrial proteins, and alters some key aspects of
mitochondrial functionality. We hypothesized that the lithocholic acid-driven
changes in mitochondrial lipidome may have a causal role in the remodeling of
mitochondrial proteome, which may in turn alter the functional state of
mitochondria to create a mitochondrial pattern that delays yeast chronological
aging. Here, we test this hypothesis by investigating how the ups1Delta,
ups2Delta and psd1Delta mutations that eliminate enzymes involved in
mitochondrial phospholipid metabolism influence the mitochondrial lipidome. We
also assessed how these mutations affect the mitochondrial proteome, influence
mitochondrial functionality and impinge on the efficiency of aging delay by
lithocholic acid. Our findings provide evidence that 1) lithocholic acid
initially creates a distinct pro-longevity pattern of mitochondrial lipidome by
proportionally decreasing phosphatidylethanolamine and cardiolipin concentrations
to maintain equimolar concentrations of these phospholipids, and by increasing
phosphatidic acid concentration; 2) this pattern of mitochondrial lipidome allows
to establish a specific, aging-delaying pattern of mitochondrial proteome; and 3)
this pattern of mitochondrial proteome plays an essential role in creating a
distinctive, geroprotective pattern of mitochondrial functionality.
PMID- 28410199
TI - Chronic intratracheal application of the soluble guanylyl cyclase stimulator BAY
41-8543 ameliorates experimental pulmonary hypertension.
AB - Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the
pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP
synthesis via sGC are important therapeutic options for treatment of PH patients.
An unwanted effect of this novel class of drugs is their systemic hypotensive
effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the
sGC stimulator BAY41-8543 could diminish its systemic vasodilating
effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal
delivery was tested in healthy rats. Four weeks after a single injection of
monocrotaline (MCT, 60 mg/kg s.c.), rats were randomized to a two-week treatment
with either placebo, BAY 41-8543 (10 mg/kg per os (PO)) or intra-tracheal (IT)
instillation (3 mg/kg or 1 mg/kg).Circulating concentrations of the drug 10 mg/kg
PO and 3 mg/kg IT were comparable. BAY 41-8543 was detected in the lung tissue
and broncho-alveolar fluid after IT delivery at higher concentrations than after
PO administration. Systemic arterial pressure transiently decreased after oral
BAY 41-8543 and was unaffected by intratracheal instillation of the drug. PO 10
mg/kg and IT 3 mg/kg regimens partially reversed pulmonary hypertension and
improved heart function in MCT-injected rats. Minor efficacy was noted in rats
treated IT with 1 mg/kg. The degree of pulmonary vascular remodeling was largely
reversed in all treatment groups.Intratracheal administration of BAY 41-8543
reverses PAH and vascular structural remodeling in MCT-treated rats. Local lung
delivery is not associated with systemic blood pressure lowering and represents
thus a further development of PH treatment with sGC stimulators.
PMID- 28410200
TI - SNORD47, a box C/D snoRNA, suppresses tumorigenesis in glioblastoma.
AB - SNORD47 is a member of the C/D box small nucleolar RNAs, which have been
implicated in cancer development. We intended to investigate the therapeutic
potential of SNORD47 in glioma. We found that the expression of SNORD47 was
downregulated in glioma tissues samples and inversely associated with advanced
tumor stage (WHO grade IV). Kaplan-Meier survival analysis revealed that glioma
patients with high SNORD47 expression had longer overall survival than those with
low SNORD47 expression. SNORD47 suppressed the proliferation of glioma cells and
induced G2 phase arrest. In addition, upregulation of SNORD47 suppressed invasion
and epithelial-mesenchymal transition in glioma cells, and combination treatment
with lenti-SNORD47 could augment the anti-tumor effect of temozolomide. These
results showed that SNORD47 acted as a tumor suppressor in glioma, and provided
the potential anti-tumor function in glioma treatment.
PMID- 28410201
TI - Incidence and survival differences in esophageal cancer among ethnic groups in
the United States.
AB - OBJECTIVES: This study was performed to identify the differences in incidence,
clinicopathological features, and survival in esophageal cancer among ethnic
groups in the United States and to determine the reasons for the differences.
RESULT: A total of 49,766 patients were included. Black and Asian groups had a
higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%,
respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non
Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic
groups declined since 1973, especially in black males. At the same time,
incidences of esophageal adenocarcinoma (EAC) dramatically increased in white
males since 1973. And incidences of ESCC and EAC were the lowest and stable in
Asian female. Multivariable models showed that patients who were male, or black,
or had larger tumors, or positive lymph nodes had an increased risk of death from
esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated
with surgery had a lower likelihood of death. For ESCC, the black patients had
the lowest DSS, while for EAC there were no significant differences in DSS among
the ethnic/racial groups. MATERIALS AND METHOD: From the Surveillance,
Epidemiology, and End Results Program database, patients diagnosed with
esophageal cancer from 1998-2013 were identified. Differences in incidences,
clinicopathological features, treatments, and disease-specific survival (DSS) in
four broad racial/ethnic groups were compared. CONCLUSION: Histological type
distribution between racial groups could be an important consideration in the
incidence and the survival trend but other factors could also have an effect.
PMID- 28410202
TI - Identification of C21orf59 and ATG2A as novel determinants of renal function
related traits in Japanese by exome-wide association studies.
AB - We have performed exome-wide association studies to identify genetic variants
that influence renal function-related traits or confer susceptibility to chronic
kidney disease or hyperuricemia in Japanese. Exome-wide association studies for
estimated glomerular filtration rate and the serum concentration of creatinine
were performed with 12,565 individuals, that for the serum concentration of uric
acid with 9934 individuals, and those for chronic kidney disease or hyperuricemia
with 5161 individuals (3270 cases, 1891 controls) or 11,686 individuals (2045
cases, 9641 controls), respectively. The relation of genotypes of single
nucleotide polymorphisms to estimated glomerular filtration rate or the serum
concentrations of creatinine or uric acid was examined by linear regression
analysis, and that of allele frequencies of single nucleotide polymorphisms to
chronic kidney disease or hyperuricemia was examined with Fisher's exact test.
The exome-wide association studies revealed that 25, seven, and six single
nucleotide polymorphisms were significantly (P <1.21 * 10-6) associated with
estimated glomerular filtration rate or the serum concentrations of creatinine or
uric acid, respectively, and that 49 and 35 polymorphisms were significantly
associated with chronic kidney disease or hyperuricemia, respectively. Subsequent
multivariable logistic regression analysis with adjustment for covariates
revealed that four and three single nucleotide polymorphisms were related (P <
0.05) to chronic kidney disease or hyperuricemia, respectively. Among
polymorphisms identified in the present study, rs76974938 [C/T (D67N)] of
C21orf59 and rs188780113 [G/A (R478C)] of ATG2A may be novel determinants of
estimated glomerular filtration rate and chronic kidney disease or of the serum
concentration of uric acid, respectively.
PMID- 28410203
TI - Exploring the key genes and pathways in enchondromas using a gene expression
microarray.
AB - Enchondromas are the most common primary benign osseous neoplasms that occur in
the medullary bone; they can undergo malignant transformation into
chondrosarcoma. However, enchondromas are always undetected in patients, and the
molecular mechanism is unclear. To identify key genes and pathways associated
with the occurrence and development of enchondromas, we downloaded the gene
expression dataset GSE22855 and obtained the differentially expressed genes
(DEGs) by analyzing high-throughput gene expression in enchondromas. In total,
635 genes were identified as DEGs. Of these, 225 genes (35.43%) were up
regulated, and the remaining 410 genes (64.57%) were down-regulated. We
identified the predominant gene ontology (GO) categories and Kyoto Encyclopedia
of Genes and Genomes (KEGG) pathways that were significantly over-represented in
the enchondromas samples compared with the control samples. Subsequently the top
10 core genes were identified from the protein-protein interaction (PPI) network.
The enrichment analyses of the genes mainly involved in two significant modules
showed that the DEGs were principally related to ribosomes, protein digestion and
absorption, ECM-receptor interaction, focal adhesion, amoebiasis and the PI3K-Akt
signaling pathway.Together, these data elucidate the molecular mechanisms
underlying the occurrence and development of enchondromas and provide promising
candidates for therapeutic intervention and prognostic evaluation. However,
further experimental studies are needed to confirm these results.
PMID- 28410204
TI - Clinical verification of plasma messenger RNA as novel noninvasive biomarker
identified through bioinformatics analysis for lung cancer.
AB - Lung cancer (LC) remains associated with significant mortality worldwide. The
lack of reliable noninvasive biomarkers and targeted therapies contributes to
poor survival rate. Herein, we initially took advantage of the public microarray
data from Oncomine database to filter messenger RNAs (mRNAs) as potential
biomarkers. Subsequently, clinical validation was applied to identify candidate
noninvasive biomarkers in plasma from patients with LC. Through comprehensive
analysis of transcriptional expression profiles across 12 studies, top 6 over-
and underexpressed mRNAs were generated. Then, a pair of matched plasma samples
from LC patient and normal control was detected by RT-PCR, and three genes with
positive bands were selected for further validation. Finally, qPCR was conducted
to further assess values of the three identified genes. We displayed with high
confidence that two cell-free mRNAs (HJURP and ADAMTS8) were expressed at
significantly levels compared to normal controls. Receiver-operating
characteristic (ROC) curves on the diagnostic efficacy of plasma HJURP and
ADAMTS8 mRNAs in LC diagnosis showed that the area under the ROC (AUC) was 0.6960
and 0.6877; sensitivity was 66.0% and 83.7%; specificity was 78.6% and 71.4%,
respectively. Combined ROC analyses using these two biomarkers revealed an
elevated AUC of 0.75. Furthermore, the higher HJURP level could be associated
with early-stage LC while lower ADAMTS8 level could be correlated with non-small
cell lung cancer. Collectively, circulating HJURP and ADAMTS8 mRNAs are promising
noninvasive biomarkers for LC diagnosis. Our integrative strategy provides new
insights into novel noninvasive biomarker identification for other types of
cancer.
PMID- 28410205
TI - Variant 2 of KIAA0101, antagonizing its oncogenic variant 1, might be a potential
therapeutic strategy in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors
worldwide and effective therapies, including molecular therapy, remain elusive.
Our previous work demonstrates that oncogenic KIAA0101 transcript variant (tv) 1
promotes HCC development and might be a HCC therapeutic target. However, the
function of another KIAA0101 variant, KIAA0101 tv2, remains unknown. In this
study, we reported that KIAA0101 tv2 was highly expressed in adjacent non
tumorous liver tissues (NTs) compared to HCC tissues. In vivo and in vitro
results showed that KIAA0101 tv2 decreased cell survival, colony formation, tumor
xenografts, migration, and invasion, as well as induced cell cycle arrest and
apoptosis. Interestingly, it could inhibit the function of KIAA0101 tv1 by
partially down-regulating KIAA0101 tv1, acting similar to KIAA0101 tv1 short
hairpin RNA (shRNA). Further studies illustrated that KIAA0101 tv2 could increase
the activity of p53 by competing with KIAA0101 tv1 for P53 binding. In
conclusion, KIAA0101 tv2 exerts anti-tumor activity in HCC and acts as an
endogenous competitor of tumor-associated KIAA0101 tv1. KIAA0101 tv2 has a
potential to work as a therapeutic drug targeting the KIAA0101 tv1 in HCC.
PMID- 28410206
TI - Development of diagnostic SCAR markers for genomic DNA amplifications in breast
carcinoma by DNA cloning of high-GC RAMP-PCR fragments.
AB - Cancer is genetically heterogeneous regarding to molecular genetic
characteristics and pathogenic pathways. A wide spectrum of biomarkers, including
DNA markers, is used in determining genomic instability, molecular subtype
determination and disease prognosis, and estimating sensitivity to different
drugs in clinical practice. In a previous study, we developed highly effective
DNA markers using improved random amplified polymorphic DNA (RAPD) with high-GC
primers, which is a valuable approach for the genetic authentication of medicinal
plants. In this study, we applied this effective DNA marker technique to generate
genetic fingerprints that detect genomic alterations in human breast cancer
tissues and then developed sequence-characterized amplified region (SCAR)
markers. Three SCAR markers (BC10-1, BC13-4 and BC31-2) had high levels of
genomic DNA amplification in breast cancer. The PHKG2 and RNF40 genes are either
overlapping or close to the sequences of SCAR marker BC13-4, while SCAR marker
BC10-1 is in the intron and overlap the DPEP1 gene, suggesting that alterations
in the expression of these genes could contribute to cancer progression.
Screening of breast cancer cell lines showed that the mRNA expression levels for
the PHKG2 and DPEP1 were lower in non-tumorigenic mammary epithelial cell MCF10A,
but elevated in other cell lines. The DPEP1 mRNA level in invasive ductal
carcinoma specimens was significantly higher than that of the adjacent normal
tissues in women. Taken together, high-GC RAMP-PCR provides greater efficacy in
measuring genomic DNA amplifications, deletion or copy number variations.
Furthermore, SCAR markers BC10-1 and BC13-4 might be useful diagnostic markers
for breast cancer carcinomas.
PMID- 28410208
TI - Tristetraprolin inhibits mitochondrial function through suppression of alpha
Synuclein expression in cancer cells.
AB - Mitochondrial dynamics play critical roles in maintaining mitochondrial
functions. Here, we report a novel mechanism for regulation of mitochondrial
dynamics mediated by tristetraprolin (TTP), an AU-rich element (ARE)-binding
protein. Overexpression of TTP resulted in elongated mitochondria, down
regulation of mitochondrial oxidative phosphorylation, reduced membrane
potential, cytochrome c release, and increased apoptotic cell death in cancer
cells. TTP overexpression inhibited the expression of alpha-Synuclein (alpha
Syn). TTP bound to the ARE within the mRNA 3'-untranslated regions (3'-UTRs) of
alpha-Syn and enhanced the decay of alpha-Syn mRNA. Overexpression of alpha-Syn
without the 3'-UTR restored TTP-induced defects in mitochondrial morphology,
mitochondrial oxidative phosphorylation, membrane potential, and apoptotic cell
death. Taken together, our data demonstrate that TTP acts as a regulator of
mitochondrial dynamics through enhancing degradation of alpha-Syn mRNA in cancer
cells. This finding will increase understanding of the molecular basis of
mitochondrial dynamics.
PMID- 28410209
TI - MiR-106b inhibitors sensitize TRAIL-induced apoptosis in hepatocellular carcinoma
through increase of death receptor 4.
AB - TNF-related apoptosis-inducing ligand (TRAIL), which is a member of the TNF
superfamily, can induce tumor cell apoptosis. However, multiple types of tumor,
including hepatocellular carcinoma, show tolerance to TRAIL. Previous studies
have demonstrated that tumor cells usually change their expression profile of
microRNA (miRNA) to obtain the ability of tolerance to drugs. However, whether
such change of miRNA on TRAIL sensitivity is seen in hepatocellular carcinoma
still needs to be explored. In this study, we observed overexpression of miR-106b
in both HCC patients' tumor tissues and cell lines. Furthermore, we found that
overexpression of miR-106b is associated with the sensitivity of TRAIL to HCC.
Silencing of miR-106b with antisense oligonucleotide (anti-miR-106b) is proved to
enhance the TRAIL-induced apoptosis and reduce the acquired drug resistance to
TRAIL in HCC. Mechanically, we didn't observe the obvious change of pro-apoptotic
proteins (Bax and Bid) and anti-apoptotic proteins (Bcl-2, Mcl-1 and Bcl-xl)
after treatment of anti-miR-106b. However, we used the methods of bioinformatics,
flow cytometry, cellular and molecular methods to prove that miR-106b directly
targeted to death receptor 4 (DR4) 3'-UTR (3'-Untranslated Regions). MiR-106b
inhibitors induced increase of DR4 expression and therefore enhancing TRAIL
mediated apoptosis in HCC. In summary, these results suggest the application of
miR-106b inhibitors in HCC treatment. Combination with miR-106b inhibitors and
TRAIL may be a novel clinical treatment method on HCC treatment in the future.
PMID- 28410210
TI - Non-invasive assessment of murine PD-L1 levels in syngeneic tumor models by
nuclear imaging with nanobody tracers.
AB - Blockade of the inhibitory PD-1/PD-L1 immune checkpoint axis is a promising
cancer treatment. Nonetheless, a significant number of patients and malignancies
do not respond to this therapy. To develop a screen for response to PD-1/PD-L1
inhibition, it is critical to develop a non-invasive tool to accurately assess
dynamic immune checkpoint expression. Here we evaluated non-invasive SPECT/CT
imaging of PD-L1 expression, in murine tumor models with varying PD-L1
expression, using high affinity PD-L1-specific nanobodies (Nbs). We generated and
characterized 37 Nbs recognizing mouse PD-L1. Among those, four Nbs C3, C7, E2
and E4 were selected and evaluated for preclinical imaging of PD-L1 in syngeneic
mice. We performed SPECT/CT imaging in wild type versus PD-L1 knock-out mice,
using Technetium-99m (99mTc) labeled Nbs. Nb C3 and E2 showed specific antigen
binding and beneficial biodistribution. Through the use of CRISPR/Cas9 PD-L1
knock-out TC-1 lung epithelial cell lines, we demonstrate that SPECT/CT imaging
using Nb C3 and E2 identifies PD-L1 expressing tumors, but not PD-L1 non
expressing tumors, thereby confirming the diagnostic potential of the selected
Nbs. In conclusion, these data show that Nbs C3 and E2 can be used to non
invasively image PD-L1 levels in the tumor, with the strength of the signal
correlating with PD-L1 levels. These findings warrant further research into the
use of Nbs as a tool to image inhibitory signals in the tumor environment.
PMID- 28410211
TI - Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is
used as a novel biomarker for hepatocellular carcinoma.
AB - Circular RNAs (circRNAs), a class of long-time-ignored noncoding RNA, have been
revealed as multifunctional RNAs in recent years. However, the diagnostic values
and the mechanism of most circRNAs in hepatocellular carcinoma (HCC) remain
unknown. In this study, we revealed that the expression level of hsa_circ_0005986
in HCC was significantly lower than that in adjacent non-tumorous tissues (P <
0.001). Its levels in HCC cell lines, HepG2, SMMC7721, Huh7, MHCC97L, MHCC97H,
and HCCLM3 were significantly lower than those in human normal hepatic cell line
L02 (P < 0.001). In addition, the low expression level of hsa_circ_0005986 was
correlated with chronic hepatitis B family history (P = 0.001), tumor diameters
(P < 0.001), microvascular invasion (P = 0.026), and Barcelona Clinic Liver
Cancer (BCLC) stage (P < 0.001). Further experiments demonstrated that both
hsa_circ_0005986 and Notch1mRNA were targets of miR-129-5p, and that
hsa_circ_0005986 downregulation liberated miR-129-5p and decreased the expression
level of Notch1mRNA. More importantly, hsa_circ_0005986 downregulation
accelerated cell proliferation by promoting the G0/G1 to S phase transition. We
conclude that hsa_circ_0005986 function as microRNA sponge in tumorigenesis and
can be used as a novel biomarker for HCC.
PMID- 28410212
TI - Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt
signaling in glioma.
AB - Gliomas are the most common form of malignant primary brain tumors with poor 5
year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5
dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and
molecular mechanism of PLOD2 in glioma have not been reported yet. In this study,
PLOD2 was found to be frequently up-regulated in glioma and could serve as an
independent prognostic marker to identify patients with poor clinical outcome.
Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma
cells in vitro and in vivo. Mechanistically, inhibition of PLOD2 inactivated
PI3K/AKT signaling pathway and thus regulated the expression of its downstream
epithelial-mesenchymal transition (EMT)-associated regulators, including E
cadherin, vimentin, N-cadherin, beta-catenin, snail and slug in glioma cells.
Moreover, PLOD2 could be induced by hypoxia-inducible factor-1alpha (HIF-1alpha)
via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data
suggests that PLOD2 may be a potential therapeutic target for patients with
glioma.
PMID- 28410213
TI - BRCA2 mutations should be screened early and routinely as markers of poor
prognosis: evidence from 8,988 patients with prostate cancer.
AB - The aim of this study was to focus on clinicopathological characteristics and
prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 (BRCA2)
gene mutation and to offer convincing evidence to consider BRCA2 mutation as a
marker of poor prognosis in the molecular classification of PCa. We searched
relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library
databases to evaluate the differences in the overall survival (OS) and cancer
specific survival (CSS) between BRCA2 mutation carriers and non-carriers in
patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers
in total from 10 studies in our meta-analysis. The results showed that carrying a
BRCA2 mutation was correlated with a reduced CSS and OS when compared with that
of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval
(CI): 2.10-3.06, P < 0.001) and 2.21 (95% CI: 1.64-2.99, P < 0.001),
respectively. The results also demonstrated that BRCA2 mutation-carriers harbored
a higher Gleason Score (GS) (> 7), TNM stage (> T3, N1, M1), and risk level than
non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor
survival outcomes in patients with prostate cancer, especially in those
undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as
a clinical prognostic factor could help stratify the high-risk patients and
provide clinical strategies for more effective targeted treatments for patients
with prostate cancer.
PMID- 28410214
TI - A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in
breast cancer.
AB - C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides
by proteolytic processing and this process is believed to be necessary for
C2ORF40 to exert cell type specific biological activity. Here, we reported a
short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human
cancer cells in vitro and in vivo. We synthesized a short peptide of human
C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological
function on cancer cell growth, migration and tumorigenesis. Cell growth assay
showed that C2ORF40 mimic peptide fragment significantly suppressed cell
proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide
fragment significantly inhibited the migration and invasion of breast cancer
cells. Furthermore, we showed that this peptide suppressed tumorigenesis in
breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic
peptide fragment suppressed the growth of tumor cells through inducing mitotic
phase arrest. In conclusion, our results firstly suggested that this short
synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.
PMID- 28410215
TI - Cardiac glycosides suppress the maintenance of stemness and malignancy via
inhibiting HIF-1alpha in human glioma stem cells.
AB - Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of
adaptive programs. We previously showed that hypoxia promotes the preferential
expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a
hypoxia inducible factor 1 alpha (HIF-1alpha)-dependent mechanism. Here, we
examined the activity of digitoxin (DT), a cardiac glycoside and a putative
inhibitor of HIF-1alpha, on human GSC in vitro and in vivo. During hypoxic
conditions (1% O2), we observed the effect of DT on the intracellular level of
HIF-1alpha and the extracellular level of vascular endothelial growth factor
(VEGF) in human GSC. We found that DT at clinically achievable concentrations,
suppressed HIF-1alpha accumulation during hypoxic conditions in human GSC and
established glioma cell lines. DT treatment also significantly attenuated hypoxia
induced expression of VEGF, a downstream target of HIF-1alpha. Exposure to DT
also reduced hypoxia-induced activation of the extracellular signal-regulated
kinase 1/2 (ERK1/2) signaling pathway. Furthermore, DT potently inhibited
neurosphere formation, and decreased CD133 expression even at concentrations that
were not overtly cytotoxic. Lastly, treatment with DT reduced GSC engraftment in
an in vivo xenograft model of glioblastoma. Intraperitoneal injections of DT
significantly inhibited the growth of established glioblastoma xenografts, and
suppressed expression of HIF-1alpha and carbonic anhydrase (CA9), a surrogate
marker of hypoxia. Taken together, these results suggest that DT at clinically
achievable concentration functions as an inhibitor of HIF-1alpha, worthy of
further investigations in the therapy of glioblastoma.
PMID- 28410216
TI - Friend leukemia virus integration 1 promotes tumorigenesis of small cell lung
cancer cells by activating the miR-17-92 pathway.
AB - Small cell lung cancer (SCLC) is regarded as the most devastative type of human
lung malignancies. The rapid and disseminated growth pattern remains the primary
cause of poor clinical prognosis in patients with SCLC. However, the molecular
factors that drive rapid progression of SCLC remain unclear. Friend leukemia
virus integration 1 (FLI1), an Ets transcription factor family member, has been
previously reported to act as a major driver of hematological malignancies. In
this study, we explored the potential role of FLI1 in SCLC. Using
immunohistochemical staining, we found that FLI1 was significantly upregulated in
SCLC tissues, compared to that in non-small cell lung cancer (NSCLC) and normal
lung tissues (p < 0.01). The expression score of FLI1 oncoprotein was associated
with the extensive stage of SCLC and the overexpressed Ki67. Knockdown of FLI1
with small interfering RNA (siRNA) or short hairpin RNA (shRNA) promoted
apoptosis and induced repression of cell proliferation, tumor colony formation
and in vivo tumorigenicity in highly aggressive SCLC cell lines. Importantly, we
discovered that FLI1 promoted tumorigenesis by activating the miR-17-92 cluster
family. This study uncovers FLI1 as an important driving factor that promotes
tumor growth in SCLC through the miR-17-92 pathway. FLI1 may serve as an
attractive target for therapeutic intervention of SCLC.
PMID- 28410218
TI - 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by
activating PPAR-gamma.
AB - 6-Shogaol, a pungent agent isolated from Zingiber officinale Roscoe, has been
known to have anti-tumor and anti-inflammatory effects. However, the anti
inflammatory effects and biological mechanism of 6-Shogaol in LPS-activated BV2
microglia remains largely unknown. In this study, we evaluated the anti
inflammatory effects of 6-Shogaol in LPS-activated BV2 microglia. 6-Shogaol was
administrated 1 h before LPS treatment. The production of inflammatory mediators
were detected by ELISA. The expression of NF-kappaB and PPAR-gamma were detected
by western blot analysis. Our results revealed that 6-Shogaol inhibited LPS
induced TNF-alpha, IL-1beta, IL-6, and PGE2 production in a concentration
dependent manner. Furthermore, 6-Shogaol inhibited LPS-induced NF-kappaB
activation by inhibiting phosphorylation and nuclear translocation of NF-kappaB
p65. In addition, 6-Shogaol could increase the expression of PPAR-gamma.
Moreover, inhibition of PPAR-gamma by GW9662 could prevent the inhibition of 6
Shogaol on LPS-induced inflammatory mediator production. In conclusion, 6-Shogaol
inhibits LPS-induced inflammation by activating PPAR-gamma.
PMID- 28410217
TI - Pterostilbene inhibits inflammation and ROS production in chondrocytes by
activating Nrf2 pathway.
AB - Pterostilbene has been reported as a potential drug to inhibit oxidative stress
and inflammation. However, the effect of pterostilbene on chondrocytes and
osteoarthritis remains to be elucidated. We sought to investigate whether
pterostilbene could protect chondrocytes from inflammation and ROS production
through factor erythroid 2-related factor 2 (Nrf2) activation. The pterostilbene
toxicity on chondrocytes collected from cartilages of Sprague-Dawley rats was
assessed by CCK-8 test. Immunofluorescence and Western blotting explored the
nuclear translocation of Nrf2. Nrf2 expression was silenced by siRNA to evaluate
the involvement of Nrf2 in the effect of pterostilbene on chondrocytes. Finally,
osteoarthritis model was established by the transection of anterior cruciate
ligament and partial medial meniscectomy in rats, and then these rats received
pterostilbene 30 mg/kg, daily, p.o. for 8 weeks. Histology and
immunohistochemistry were used to assess histopathological change and Nrf2
expression in cartilage. Nuclear translocation of Nrf2 was stimulated by
pterostilbene without cellular toxicity. Pterostilbene inhibited the level of COX
2, iNOS, PGE2, and NO, as well as the mitochondrial and total intracellular ROS
production induced by IL-1beta in chondrocytes, partially reversed by the Nrf2
silencing. Pterostilbene prevented cartilage degeneration and promoted the
nuclear translocation of Nrf2 in cartilage. These results suggest that
pterostilbene could inhibit the IL-1beta-induced inflammation and ROS production
in chondrocytes by stimulating the nuclear translocation of Nrf2.
PMID- 28410220
TI - Reprogramming induced by isoliquiritigenin diminishes melanoma cachexia through
mTORC2-AKT-GSK3beta signaling.
AB - Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor
activity in vitro and in vivo. The effect of ISL on reprogramming in cancer
cells, however, remains elusive. In this study, we investigated the effect of ISL
on reprogramming in human melanoma A375 cells. ISL (15 MUg/ml) significantly
inhibited A375 cell proliferation, anchorage independent cell proliferation and
G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no
significant changes in apoptosis rate. Terminal differentiation indicators
(melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were
all up-regulated by ISL treatment. In ISL-treated cells, glucose uptake, lactate
levels and mRNA expression levels of GLUT1 and HK2 were significantly decreased,
and accompanied by an increase in O2 consumption rate (OCR) and adenosine
triphosphate (ATP) deficiency. Protein expression levels of mTORC2-AKT-GSK3beta
signaling pathway components (mTOR, p-mTOR, RICTOR, p-AKT, p-GSK3beta) decreased
significantly after ISL treatment. Co-treatment of ISL and the mTOR-specific
inhibitor Ku-0063794 had a synergistic effect on the inhibition of proliferation,
and increased melanin content and TYR activity. Glucose uptake and lactate levels
decreased more significantly than treatment with ISL alone. These findings
indicate that ISL induced reprogramming in A375 melanoma cells by activating
mTORC2-AKT-GSK3beta signaling.
PMID- 28410221
TI - Discovery and characterization of small molecule Rac1 inhibitors.
AB - Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types,
including pancreatic cancer. Rac1 activates multiple signaling pathways that lead
to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1
activity is a viable therapeutic strategy for proliferative disorders such as
cancer. Here we identified small molecule inhibitors that target the nucleotide
binding site of Rac1 through in silico screening. Follow up in vitro studies
demonstrated that two compounds blocked active Rac1 from binding to its effector
PAK1. Fluorescence polarization studies indicate that these compounds target the
nucleotide-binding site of Rac1. In cells, both compounds blocked Rac1 binding to
its effector PAK1 following EGF-induced Rac1 activation in a dose-dependent
manner, while showing no inhibition of the closely related Cdc42 and RhoA
activity. Furthermore, functional studies indicate that both compounds reduced
cell proliferation and migration in a dose-dependent manner in multiple
pancreatic cancer cell lines. Additionally, the two compounds suppressed the
clonogenic survival of pancreatic cancer cells, while they had no effect on the
survival of normal pancreatic ductal cells. These compounds do not share the core
structure of the known Rac1 inhibitors and could serve as additional lead
compounds to target pancreatic cancers with high Rac1 activity.
PMID- 28410222
TI - Dietary score and the risk of oral cancer: a case-control study in southeast
China.
AB - This study aims to develop a simple dietary score to comprehensively evaluate the
role of diet in the risk of oral cancer. A case-control study including 930 oral
cancer cases and 2667 frequency-matched controls was performed in Fujian, China.
Unconditional logistic regression model was used to estimate the effects of
dietary factors on oral cancer. After adjustment for potential confounders, less
intake of domestic meat (< 3 times per week), fish (< 3 times per week), seafood
(< 3 times per week), leafy vegetables (< 1 time per day), other vegetables (< 1
time per day), fruits (< 3 times per week), milk and dairy products (< 1 time per
week) and eggs (< 5 times per week) were significant risk factors for oral
cancer. Then these variables were incorporated to establish dietary risk score.
Assessed by the receiver operating characteristic curve, the score showed a
satisfactory discriminatory capacity, with an area under the curve of 0.682 (95%
CI: 0.662-0.702). Moreover, the score was positively associated with the risk of
oral cancer as quartiles, and the association was apparently stronger in tobacco
smokers or alcohol drinkers. Additionally, there were significant multiplicative
interactions between the score and tobacco smoking or alcohol drinking for oral
cancer. In the present study, a convenient dietary score with satisfactory
discriminatory capacity was developed to assess the collected effect of dietary
factors on oral cancer, which could provide a new strategy for the prevention of
oral cancer through changing in dietary habits.
PMID- 28410223
TI - Interleukin-10 rs1800896 polymorphism is associated with increased head and neck
cancer risk but not associated with its clinical stages.
AB - BACKGROUND: The association of interleukin-10 rs1800896 polymorphism with head
and neck cancer risk and its clinical stages has been investigated by many
published studies, but the results remain inconsistent. Therefore, we conducted
this meta-analysis for further investigation. RESULTS: Six case-control studies
involving 1,781 head and neck cancer patients and 1,978 controls were yielded.
The results indicated an association between rs1800896 polymorphism and increased
head and neck risk [odds ratio (95%confidence interval) for G vs. A, GA vs. AA,
GG vs. AA, GA+GG vs. AA, and GG vs. AA + GA were 1.63 (1.30-2.04), 3.17 (2.11
4.76), 1.63 (1.17-2.26), 1.73 (1.25-2.39), and 2.73 (1.82-4.09), respectively].
The subgroup analyses all obtained similar results with overall populations. The
results of clinical stages yielded a non-significant association. No publication
bias was detected. MATERIALS AND METHODS: The PubMed and Chinese National
Knowledge Infrastructure databases were searched up to December 27, 2016. Two
authors independently selected studies, extracted and analyzed the data using the
RevMan 5 software. Either a fixed effect or a random effect model was used to
estimate pooled odds ratio and its 95% confidence intervals. CONCLUSIONS: We
concluded that interleukin-10 rs1800896 polymorphism was significantly associated
with head and neck cancer risk but not with the clinical stages thereof.
PMID- 28410224
TI - Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial
cells through miR-21/VEGF signal.
AB - Glioma stem cells (GSCs) play an important role in glioblastoma prognosis.
Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs).
Glioblastoma has a high level of miR-21 which could upregulate vascular
endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promote
the angiogenic ability of endothelial cells (ECs) through miR-21/VEGF signal.
GSCs were isolated from U-251 cells with stem cell marker CD133. GSCs transfected
without or with scramble or miR-21 mimics were used to produce GSC-EXscon, GSC
EXssc and GSC-EXsmiR-21. Human brain ECs were co-cultured with vehicle, GSC
EXscon, GSC-EXssc or GSC-EXsmiR-21 plus VEGF siRNAs (siRNAVEGF). After 24 hours,
the angiogenic abilities of ECs were evaluated. The levels of miR-21, VEGF and p
Flk1/VEGFR2 were determined. Results showed: 1) Over 90% of purified GSCs
expressed CD133; 2) The levels of miR-21 and VEGF in GSCs and GSC-EXs were up
regulated by miR-21 mimic transfection; 3) Compared to GSC-EXscon or GSC-EXssc,
GSC-EXsmiR-21 were more effective in elevating the levels of miR-21 and VEGF, and
the ratio of p-Flk1/VEGFR2 in ECs; 4) GSC-EXsmiR-21 were more effective in
promoting the angiogenic ability of ECs than GSC-EXscon or GSC-EXssc, which were
remarkably reduced by siRNAVEGF pretreatment. In conclusion, GSC-EXs can promote
the angiogenic ability of ECs by stimulating miR-21/VEGF/VEGFR2 signal pathway.
PMID- 28410225
TI - Sentinel lymph node mapping in endometrial cancer: a systematic review and meta
analysis.
AB - Endometrial cancer is the most frequent tumor in the female reproductive system,
while the sentinel lymph node (SLN) mapping for diagnostic efficacy of
endometrial cancer is still controversial. This meta-analysis was conducted to
evaluate the diagnostic value of SLN in the assessment of lymph nodal involvement
in endometrial cancer. Forty-four studies including 2,236 cases were identified.
The pooled overall detection rate was 83% (95% CI: 80-86%). The pooled
sensitivity was 91% (95% CI: 87-95%). The bilateral pelvic node detection rate
was 56% (95% CI: 48-64%). Use of indocyanine green (ICG) increased the overall
detection rate to 93% (95% CI: 89-96%) and robotic-assisted surgery also
increased the overall detection rate to 86% (95% CI: 79-93%). In summary, our
meta-analysis provides strong evidence that sentinel node mapping is an accurate
and feasible method that performs well diagnostically for the assessment of lymph
nodal involvement in endometrial cancer. Cervical injection, robot-assisted
surgery, as well as using ICG, optimized the sensitivity and detection rate of
the technique. Sentinel lymph mapping may potentially leading to a greater
utilization by gynecologic surgeons in the future.
PMID- 28410226
TI - Use of acetaminophen and risk of endometrial cancer: evidence from observational
studies.
AB - Previous meta-analyses suggested that aspirin was associated with reduced risk of
endometrial cancer. However, there has been no study comprehensively summarize
the evidence of acetaminophen use and risk of endometrial cancer from
observational studies. We systematically searched electronic databases (PubMed ,
EMBASE, Web of Science, and Cochrane Library) for relevant cohort or case-control
studies up to February 28, 2017. Two independent authors performed the
eligibility evaluation and data extraction. All differences were resolved by
discussion. A random-effects model was applied to estimate summary relative risks
(RRs) with 95% CIs. All statistical tests were two-sided. Seven observational
studies including four prospective cohort studies and three case-control studies
with 3874 endometrial cancer cases were included for final analysis. Compared
with never use acetaminophen, ever use this drug was not associated with risk of
endometrial cancer (summarized RR = 1.02; 95% CI: 0.93-1.13, I2 = 0%). Similar
null association was also observed when compared the highest category of
frequency/duration with never use acetaminophen (summarized RR = 0.88; 95% CI:
0.70-1.11, I2 = 15.2%). Additionally, the finding was robust in the subgroup
analyses stratified by study characteristics and adjustment for potential
confounders and risk factors. There was no evidence of publication bias by a
visual inspection of a funnel plot and formal statistical tests. In summary, the
present meta-analysis reveals no association between acetaminophen use and risk
of endometrial cancer. More large scale prospective cohort studies are warranted
to confirm our findings and carry out the dose-response analysis of
aforementioned association.
PMID- 28410227
TI - Subcloning and characterization of highly metastatic cells derived from human
esophageal squamous cell carcinoma KYSE150 cells by in vivo selection.
AB - Esophageal cancer is the eighth most common cancer and the sixth most common
cause of cancer-related deaths worldwide. Despite the research progress in
understanding the disease, the mechanism underlying the metastasis is still
unclear. Here, we successfully generated a highly metastatic cell subline,
designated as KYSE150-LuM, derived from an esophageal squamous cell carcinoma
cell line (KYSE150) by in vivo selection. To elucidate the mechanisms driving
metastasis, we characterized the gene expression differences between LuM cells
and parent KYSE150 cells. IL-6, IL-1beta, and LCN2, previously associated with
tumor growth and metastasis, were up-regulated in LuM cells. Recent studies on
cancer have increasingly focused on the tumor microenvironment, from which these
cytokines are released. The fact that these three cytokines (IL-6, IL-1beta,
LCN2) were up-regulated in LuM cells indicates that these highly metastatic cells
obtained through in vivo selection will be a useful resource for further studies
on elucidating the mechanisms underlying the tumor microenvironment which is
associated with cytokine-related tumor growth and metastasis. Moreover, LuM cells
could disseminate to the lung in shorter period of time in vivo, indicating their
utility for in vivo experiments of metastasis and new therapeutic targets in a
shorter period of time than currently possible.
PMID- 28410228
TI - Identification of a novel functional JAK1 S646P mutation in acute lymphoblastic
leukemia.
AB - The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching
90%, while the prognosis of adults remains poor due to the limited therapeutic
approaches. In order to identify new targets for ALL, we performed whole-exome
sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P
mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two
cases exhibited A639G and P960S mutations separately. Functional studies
demonstrated that only JAK1 S646P mutation could activate multiple signaling
pathways, drive cytokine-independent cell growth, and promote proliferation of
malignant cells in nude mice. Moreover, a high sensitivity to the JAK1/2
inhibitor ruxolitinib was observed in S646P mutant model. Exploration in a total
of 209 ALL cases showed that JAK1 mutations occur at a frequency of 10.5% in T
ALL (2/19) and 1.6% in B-ALL (3/190). Collectively, our results suggested that
JAK1 S646P is an activating mutation in vitro and in vivo. JAK-STAT pathway might
represent a promising therapeutic target for ALL.
PMID- 28410229
TI - In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF
1alpha by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal
carcinoma using micro 18F-FDG PET/CT.
AB - PURPOSE: Hypoxia-inducible factor 1alpha (HIF-1alpha) and glucose transporter-1
(GLUT-1) are two important hypoxic markers associated with the radioresistance of
cancers including laryngeal carcinoma. We evaluated whether the simultaneous
inhibition of GLUT-1 and HIF-1alpha expression improved the radiosensitivity of
laryngeal carcinoma. We explored whether the expression of HIF-1alpha and GLUT-1
was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and
whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was
appropriate for early evaluation of the response of laryngeal carcinoma to
targeted treatment in vivo. MATERIALS AND METHODS: To verify the above
hypotheses, an in vivo model was applied by subcutaneously injecting Hep-2 (2 *
107/mL * 0.2 mL) and Tu212 cells (2 * 107/mL * 0.2 mL) into nude mice. The
effects of HIF-1alpha antisense oligodeoxynucleotides (AS-ODNs) (100 MUg) and
GLUT-1 AS-ODNs (100 MUg) on the radiosensitivity of laryngeal carcinoma were
assessed by tumor volume and weight, microvessel density (MVD), apoptosis index
(AI) and necrosis in vivo based on a full factorial (23) design. 18F-FDG-PET/CT
was taken before and after the treatment of xenografts. The relationships between
HIF-1alpha and GLUT-1 expression and 18F-FDG uptake in xenografts were estimated
and the value of 18F-FDG-PET/CT was assessed after treating the xenografts.
RESULTS: 10 Gy X-ray irradiation decreased the weight of Hep-2 xenografts 8 and
12 days after treatment, and the weights of Tu212 xenografts 8 days after
treatment. GLUT-1 AS-ODNs decreased the weight of Tu212 xenografts 12 days after
treatment. There was a synergistic interaction among the three treatments (GLUT-1
AS-ODNs, HIF-1alpha AS-ODNs and 10Gy X-ray irradiation) in increasing apoptosis,
decreasing MVD, and increasing necrosis in Hep-2 xenografts 8 days after
treatment (p < 0.05) and in Tu212 xenografts 12 days after treatment (p < 0.001).
Standardized uptake value (tumor/normal tissue)( SUVmaxT/N) did not show a
statistically significant correlation with GLUT1 and HIF-1alpha expression and
therapeutic effect (necrosis, apoptosis). CONCLUSIONS: Simultaneous inhibition of
HIF-1alpha and GLUT-1 expression might increase the radiosensitivity of laryngeal
carcinoma, decreasing MVD, and promoting apoptosis and necrosis. 18F-FDG-PET/CT
wasn't useful in evaluating the therapeutic effect on laryngeal cancer in this
animal study.
PMID- 28410230
TI - Insulin growth factor binding protein 2 mediates the progression of
lymphangioleiomyomatosis.
AB - Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease that almost
exclusively affects women. LAM cells migrate to the lungs, where they cause
cystic destruction of lung parenchyma. Mutations in TSC1 or TSC2 lead to the
activation of the mammalian target of rapamycin complex-1, a kinase that
regulates growth factor-dependent protein translation, cell growth, and
metabolism. Insulin-like growth factor binding protein 2 (IGFBP2) binds insulin,
IGF1 and IGF2 in circulation, thereby modulating cell survival, migration, and
invasion in neoplasms. In this study, we identified that IGFBP2 primarily
localized in the nucleus of TSC2-null LAM patient-derived cells in vitro and in
vivo. We also showed that nuclear accumulation of IGFBP2 is closely associated
with estrogen receptor alpha (ERa) expression. Furthermore, estrogen treatment
induced IGFBP2 nuclear translocation in TSC2-null LAM patient-derived cells.
Importantly, depletion of IGFBP2 by siRNA reduced cell proliferation, enhanced
apoptosis, and decreased migration and invasion of TSC2-null LAM patient-derived
cells. More interestingly, depletion of IGFBP2 markedly decreased the
phosphorylation of MAPK in LAM patient-derived TSC2-null cells. Collectively,
these results suggest that IGFBP2 plays an important role in promoting
tumorigenesis, through estrogen and ERalpha signaling pathway. Thus, targeting
IGFBP2 may serve as a potential therapeutic strategy for women with LAM and other
female gender specific neoplasms.
PMID- 28410231
TI - Genetic alterations in seborrheic keratoses.
AB - Seborrheic keratoses are common benign epidermal lesions that are associated with
increased age and sun-exposure. Those lesions despite harboring multiple somatic
alterations in contrast to malignant tumors appear to be genetically stable. In
order to investigate and characterize the presence of recurrent mutations, we
performed exome sequencing on DNA from one seborrheic keratosis lesion and
corresponding blood cells from the same patients with follow up investigation of
alterations identified by exome sequencing in 24 additional lesions from as many
patients. In addition we investigated alterations in all lesions at specific
genes loci that included FGFR3, PIK3CA, HRAS, BRAF, CDKN2A and TERT and DHPH3
promoters. The exome sequencing data indicated three mutations per Mb of the
targeted sequence. The mutational pattern depicted typical UV signature with
majority of alterations being C>T and CC>TT base changes at dipyrimidinic sites.
The FGFR3 mutations were the most frequent, detected in 12 of 25 (48%) lesions,
followed by the PIK3CA (32%), TERT promoter (24%) and DPH3 promoter mutations
(24%). TERT promoter mutations associated with increased age and were present
mainly in the lesions excised from head and neck. Three lesions also carried
alterations in CDKN2A. FGFR3, TERT and DPH3 expression did not correlate with
mutations in the respective genes and promoters; however, increased FGFR3
transcript levels were associated with increased FOXN1 levels, a suggested
positive feedback loop that stalls malignant progression. Thus, in this study we
report overall mutation rate through exome sequencing and show the most frequent
mutations seborrheic keratosis.
PMID- 28410232
TI - Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated
by TRPM7 activity induced by exogenous ATP.
AB - Glioblastomas (GBM) are the most malignant brain tumors in humans and have a very
poor prognosis. New therapeutic options are urgently needed. A novel drug,
Vacquinol-1 (Vac), a quinolone derivative, displays promising properties by
inducing rapid cell death in GBM but not in non-transformed tissues. Features of
this type of cell death are compatible with a process termed methuosis. Here we
tested Vac on a highly malignant glioma cell line observed by long-term video
microscopy. Human dental-pulp stem cells (DPSCs) served as controls. A major
finding was that an exogenous ATP concentration of as little as 1 MUM counter
regulated the Vac-induced cell death. Studies using carvacrol, an inhibitor of
transient receptor potential cation channel, subfamily M, member 7 (TRPM7),
demonstrated that the ATP-inducible inhibitory effect is likely to be via TRPM7.
Exogenous ATP is of relevance in GBM with large necrotic areas. Our results
support the use of GBM cultures with different grades of malignancy to address
their sensitivity to methuosis. The video-microscopy approach presented here
allows decoding of signaling pathways as well as mechanisms of chemotherapeutic
resistance by long-term observation. Before implementing Vac as a novel
therapeutic drug in GBM, cells from each individual patient need to be assessed
for their ATP sensitivity. In summary, the current investigation supports the
concept of methuosis, described as non-apoptotic cell death and a promising
approach for GBM treatment. Tissue-resident ATP/necrosis may interfere with this
cell-death pathway but can be overcome by a natural compound, carvacrol that even
penetrates the blood-brain barrier.
PMID- 28410233
TI - Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro
growth.
AB - Uterine leiomyomas (UL) are the most prevalent symptomatic human tumors at all
and somatic mutations of the gene encoding mediator subcomplex 12 (MED12)
constitute the most frequent driver mutations in UL. Recently, a rapid loss of
mutated cells during in vitro growth of UL-derived cell cultures was reported,
resulting in doubts about the benefits of UL-derived cell cultures. To evaluate
if the rapid loss of MED12-mutated cells in UL cell cultures depends on in vitro
passaging, we set up cell cultures from nine UL from 40-50 year old Caucasian
patients with at least one UL. Cultured UL cells were investigated for loss of
MED12-mutated cells. Genetic characterization of native tumor samples and
adjacent myometrium was done by array analysis. "Aged" primary cultures without
passaging were compared to cells of three subsequent passages. Comparative
analyses of the mutated/non-mutated ratios between native tissue, primary cells,
and cultured tumor cells revealed a clear decrease of MED12-mutated cells. None
of the tumors showed gross alterations of the array profiles, excluding the
presence of gross genomic imbalances besides the MED12 mutations as a reason for
the intertumoral variation in the loss of MED12-mutated cells. Albeit at a lesser
rate, loss of MED12-mutated cells from cell cultures of UL occurs even without
passaging thus indicating the requirement of soluble factors or matrix components
lacking in vitro. Identification of these factors can help to understand the
mechanisms of the growth of the most frequent type of uterine leiomyomas and to
decipher novel drug targets.
PMID- 28410234
TI - The ovarian cancer oncobiome.
AB - Humans and other mammals are colonized by microbial agents across the kingdom
which can represent a unique microbiome pattern. Dysbiosis of the microbiome has
been associated with pathology including cancer. We have identified a microbiome
signature unique to ovarian cancers, one of the most lethal malignancies of the
female reproductive system, primarily because of its asymptomatic nature during
the early stages in development. We screened ovarian cancer samples along with
matched, and non-matched control samples using our pan-pathogen array
(PathoChip), combined with capture-next generation sequencing. The results show a
distinct group of viral, bacterial, fungal and parasitic signatures of high
significance in ovarian cases. Further analysis shows specific viral integration
sites within the host genome of tumor samples, which may contribute to the
carcinogenic process. The ovarian cancer microbiome signature provides insights
for the development of targeted therapeutics against ovarian cancers.
PMID- 28410235
TI - Cysteinyl leukotriene receptor 1 facilitates tumorigenesis in a mouse model of
colitis-associated colon cancer.
AB - Cysteinyl leukotriene receptor 1 (CysLT1R) has been shown to be up-regulated in
the adenocarcinomas of colorectal cancer patients, which is associated with a
poor prognosis. In a spontaneous model of colon cancer, CysLT1R disruption was
associated with a reduced tumor burden in double-mutant female mice
(ApcMin/+/Cysltr1-/-) compared to ApcMin/+ littermates. In the current study, we
utilized a genetic approach to investigate the effect of CysLT1R in the induced
azoxymethane/dextran sulfate sodium (AOM/DSS) model of colitis-associated colon
cancer. We found that AOM/DSS female mice with a global disruption of the Cysltr1
gene (Cysltr1-/-) had a higher relative body weight, a more normal weight/length
colon ratio and smaller-sized colonic polyps compared to AOM/DSS wild-type
counterparts. The Cysltr1-/- colonic polyps exhibited low-grade dysplasia, while
wild-type polyps had an adenoma-like phenotype. The Cysltr1-/- colonic polyps
exhibited significant decreases in nuclear beta-catenin and COX-2 protein
expression, while the normal crypts surrounding the polyps exhibited increased
Mucin 2 expression. Furthermore, Cysltr1-/- mice exhibited an overall reduction
in inflammation, with a significant decrease in proinflammatory cytokines, polyp
5-LOX expression and infiltration of CD45 leukocytes and F4/80 macrophages. In
conclusion, the present genetic approach in an AOM/DSS model further supports an
important role for CysLT1R in colon tumorigenesis.
PMID- 28410236
TI - Development of new prognostic model based on pretreatment betaLRI and LLRI for
stage IE/IIE upper aerodigestive tract ENKTL, nasal type.
AB - To identify simple non-invasive prognostic factors for extranodal natural
killer/T cell lymphoma (ENKTL), we have investigated the prognostic value of
pretreatment beta2-microglobin to lymphocytes ratio index (betaLRI) or lactate
dehydrogenase to lymphocytes ratio index (LLRI), by analyzing the retrospective
data from 211 ENKTL patients. Receiver operating characteristic (ROC) curve
analysis was performed to determine the cut-off value of pretreatment betaLRI and
LLRI. The univariate analysis indicated that Ann Arbor Stage (p = 0.008), Eastern
Cooperative Oncology Group score (ECOG) (p = 0.009), International Prognostic
Index (IPI) (p = 0.023), betaLRI (p = 0.003), LLRI (p = 0.04), neutrophil
lymphocyte ratio index (p = 0.025) and monocyte/granulocyte to lymphocyte ratio
(p = 0.030) were significantly associated with overall survival (OS) in ENKTL
patients. However, multivariate analysis demonstrated that only Ann Arbor Stage
(p = 0.028), betaLRI (p < 0.001) and LLRI (p = 0.006) were only correlated
independently with OS. Furthermore, betaLRI and LLRI based new prognostic model
showed improved discrimination for stage IE/IIE upper aerodigestive tract in
ENKTL patients than IPI and Korean Prognostic Index. Overall, our study concluded
that new betaLRI-based prognosis model is useful to stratify ENKTL patients and
higher betaLRI and LLRI can act as independent prognostic predictor candidates in
early stage ENKTL.
PMID- 28410238
TI - Physical activity and telomere length: Impact of aging and potential mechanisms
of action.
AB - Telomeres protect the integrity of information-carrying DNA by serving as caps on
the terminal portions of chromosomes. Telomere length decreases with aging, and
this contributes to cell senescence. Recent evidence supports that telomere
length of leukocytes and skeletal muscle cells may be positively associated with
healthy living and inversely correlated with the risk of several age-related
diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic
pain, and stress. In observational studies, higher levels of physical activity or
exercise are related to longer telomere lengths in various populations, and
athletes tend to have longer telomere lengths than non-athletes. This
relationship is particularly evident in older individuals, suggesting a role of
physical activity in combating the typical age-induced decrements in telomere
length. To date, a small number of exercise interventions have been executed to
examine the potential influence of chronic exercise on telomere length, but these
studies have not fully established such relationship. Several potential
mechanisms through which physical activity or exercise could affect telomere
length are discussed, including changes in telomerase activity, oxidative stress,
inflammation, and decreased skeletal muscle satellite cell content. Future
research is needed to mechanistically examine the effects of various modalities
of exercise on telomere length in middle-aged and older adults, as well as in
specific clinical populations.
PMID- 28410239
TI - Homoharringtonine suppresses imatinib resistance via the Bcl-6/p53 pathway in
chronic myeloid leukemia cell lines.
AB - BACKGROUND: The anti-leukemic mechanism of homoharringtonine (HHT) differs from
that of IM, and HHT is one of the most useful agents for use in patients with IM
resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the
sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the
Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in
vitro and in vivo. RESULTS: Ph+ acute lymphoblastic leukemia (ALL) cells and IM
resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6
protein. Bcl-6 mediated the upregulation of p53, and and Bcl-6 induced growth
inhibition of IM-resistant cells as well as its apoptosis by targeting p53. In
addition, Bcl-6 was downregulated moderately after HHT treatment in different
cells. The Bcl-6 expression was significantly increased in patients with CML when
compared with healthy subjects. Furthermore, the expression of Bcl-6 was higher
in patients with CML-blastic phase (CML-BP) than in those with CML-chronic phase
(CML-CP). METHODS: The inhibitory effect of drugs on cell growth was detected by
Cell Counting Kit-8 (CCK-8), The apoptosis rate and the cell cycle were
investigated by flow cytometry. The expression of Bcl-6, p53, Bcl-2, caspase9,
and caspase3 proteins was assayed by western blot, Real- Time PCR (qPCR) detect
Bcl-6 and p53 mRNA. CONCLUSIONS: HHT can suppress the growth and induce apoptosis
of IM-resistant cells, the mechanism of which is associated with blocking of the
Bcl-6/p53 pathway. Our results could offer a theoretical explanation for HHT use
in patients with IM resistance or intolerance.
PMID- 28410237
TI - Combination therapy in combating cancer.
AB - Combination therapy, a treatment modality that combines two or more therapeutic
agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs
enhances efficacy compared to the mono-therapy approach because it targets key
pathways in a characteristically synergistic or an additive manner. This approach
potentially reduces drug resistance, while simultaneously providing therapeutic
anti-cancer benefits, such as reducing tumour growth and metastatic potential,
arresting mitotically active cells, reducing cancer stem cell populations, and
inducing apoptosis. The 5-year survival rates for most metastatic cancers are
still quite low, and the process of developing a new anti-cancer drug is costly
and extremely time-consuming. Therefore, new strategies that target the survival
pathways that provide efficient and effective results at an affordable cost are
being considered. One such approach incorporates repurposing therapeutic agents
initially used for the treatment of different diseases other than cancer. This
approach is effective primarily when the FDA-approved agent targets similar
pathways found in cancer. Because one of the drugs used in combination therapy is
already FDA-approved, overall costs of combination therapy research are reduced.
This increases cost efficiency of therapy, thereby benefiting the "medically
underserved". In addition, an approach that combines repurposed pharmaceutical
agents with other therapeutics has shown promising results in mitigating tumour
burden. In this systematic review, we discuss important pathways commonly
targeted in cancer therapy. Furthermore, we also review important repurposed or
primary anti-cancer agents that have gained popularity in clinical trials and
research since 2012.
PMID- 28410240
TI - Ulk1 over-expression in human gastric cancer is correlated with patients' T
classification and cancer relapse.
AB - Ulk1 is a key autophagy protein. Here, we tested expression and potential
function of Ulk1 in human gastric cancer. Ulk1 mRNA and protein were
significantly elevated in multiple fresh human gastric cancer tissues. Its level
was relatively low in surrounding normal epithelial tissues. Ulk1 over-expression
was also observed in several gastric cancer cell lines (AGS, HGC-27, and SNU601).
Remarkably, Ulk1 knockdown by targeted-shRNA inhibited AGS gastric cancer cell
survival and proliferation. On the other hand, exogenous Ulk1 over-expression
could further promote AGS cell survival and proliferation. Immunohistochemistry
(IHC) staining assay of 145 paraffin-embedded gastric cancer tissues showed that
Ulk1 was over-expressed in majority (114 out of 145) of gastric cancer tissues.
Importantly, high Ulk1 expression in gastric cancer was correlated with patients'
T classification and cancer relapse. Together, we demonstrate that Ulk1 over
expression in human gastric cancer is pro-survival. Its over-expression is
associated with patients' T classification and cancer relapse.
PMID- 28410241
TI - Prognostic role of the long non-coding RNA, SPRY4 Intronic Transcript 1, in
patients with cancer: a meta-analysis.
AB - Recent studies have emphasized the important role of long non-coding RNAs
(lncRNAs) in cancer development. The present study performed a meta-analysis to
investigate whether lncRNA, SPRY4 Intronic Transcript 1(SPRY4-IT1) can be served
as a potential biomarker for prognosis in human cancers. The eligible studies
were collected by searching multiple online databases (Pubmed, EMBASE, CNKI, Web
of Science and Google Scholar) and meta-analysis was performed to explore the
association between the expression levels of SPRY4-IT1 and overall survival (OS),
disease-free survival (DFS) and clinicopathological parameters. A total of 1329
patients from 13 studies were included for meta-analysis. The meta-analysis
results showed that high expression level of SPRY4-IT1 was significantly
associated with shorter OS in cancer patients (HR = 3.20, 95% CI: 2.59-3.90,
P<0.001) except in the patients with non-small cell lung cancer (NSCLC).
Increased SPRY4-IT1 expression level was correlated with shorter DFS in patients
with gastric cancer and ovarian cancer. SPRY4-IT1 expression level was not
correlated with the clinicopathological parameters including age (P = 0.37),
gender (P = 0.87), tumor size (P = 0.47) and invasion depth (P = 0.52), and
increased SPRY4-IT1 expression level was significantly associated with distant
metastasis (odds ratio (OR) = 1.96, 95% CI: 1.24-3.08, P = 0.004), lymph node
metastasis (OR = 3.96, 95% CI: 1.48-5.54, P<0.001), advanced
tumor/node/metastasis stage (OR = 3.72, 95% CI = 2.91-4.76, P<0.001) and poor
tumor differentiation (OR = 1.86, 95% CI = 1.35-2.58, P<0.001) in cancer patients
except in patients with NSCLC. In summary, the meta-analysis results suggested
that increased expression level of SPRY4-IT1 was positively associated with
unfavorable prognosis and advanced features of cancers in cancer patients but not
in patients with NSCLC.
PMID- 28410243
TI - Impact of perioperative blood transfusion on clinical outcomes in patients with
colorectal liver metastasis after hepatectomy: a meta-analysis.
AB - BACKGROUND: Perioperative blood transfusion may be associated with negative
clinical outcomes in oncological surgery. A meta-analysis of published studies
was conducted to evaluate the impact of blood transfusion on short- and long-term
outcomes following liver resection of colorectal liver metastasis (CLM).
MATERIALS AND METHODS: A systematic search was performed to identify relevant
articles. Data were pooled for meta-analysis using Review Manager version 5.3.
RESULTS: Twenty-five observational studies containing 10621 patients were
subjected to the analysis. Compared with non-transfused patients, transfused
patients experienced higher overall morbidity (odds ratio [OR], 1.98; 95%
confidence intervals [CI] =1.49-2.33), more major complications (OR, 2.12; 95% CI
=1.26-3.58), higher mortality (OR, 4.13; 95% CI =1.96-8.72), and longer length of
hospital stay (weighted mean difference, 4.43; 95% CI =1.15-7.69). Transfusion
was associated with reduced overall survival (risk ratio [RR], 1.24, 95% CI =1.11
1.38) and disease-free survival (RR, 1.38, 95% CI=1.23-1.56). CONCLUSION:
Perioperative blood transfusion has a detrimental impact on the clinical outcomes
of patients undergoing CLM resection.
PMID- 28410245
TI - Rivaroxaban Associated Cholestatic Jaundice.
PMID- 28410242
TI - Functional and therapeutic significance of EZH2 in urological cancers.
AB - The enhancer of zeste homolog 2 (EZH2) is a core subunit of the polycomb
repressor complex 2 (PRC2), which is overexpressed in numerous cancers and
mutated in several others. Notably, EZH2 acts not only a critical epigenetic
repressor through its role in histone methylation, it is also an activator of
gene expression, acting through multiple signaling pathways in distinct cancer
types. Increasing evidence suggests that EZH2 is an oncogene and is central to
initiation, growth and progression of urological cancers. In this review, we
highlight the critical role of EZH2 as a master regulator of tumorigenesis in the
prostate, bladder and the kidney through epigenetic control of transcription as
well as a modulation of various critical signaling pathways. We also discuss the
promise and challenges for EZH2 inhibitors as future anticancer therapeutics,
some of which are currently in clinical trials.
PMID- 28410244
TI - Platelet-derived growth factor receptor-alpha positive cardiac progenitor cells
derived from multipotent germline stem cells are capable of cardiomyogenesis in
vitro and in vivo.
AB - Cardiac cell therapy has the potential to revolutionize treatment of heart
diseases, but its success hinders on the development of a stem cell therapy
capable of efficiently producing functionally differentiated cardiomyocytes. A
key to unlocking the therapeutic application of stem cells lies in understanding
the molecular mechanisms that govern the differentiation process. Here we report
that a population of platelet-derived growth factor receptor alpha (PDGFRA) cells
derived from mouse multipotent germline stem cells (mGSCs) were capable of
undergoing cardiomyogenesis in vitro. Cells derived in vitro from PDGFRA positive
mGSCs express significantly higher levels of cardiac marker proteins compared to
PDGFRA negative mGSCs. Using Pdgfra shRNAs to investigate the dependence of
Pdgfra on cardiomyocyte differentiation, we observed that Pdgfra silencing
inhibited cardiac differentiation. In a rat myocardial infarction (MI) model,
transplantation of a PDGFRAenriched cell population into the rat heart readily
underwent functional differentiation into cardiomyocytes and reduced areas of
fibrosis associated with MI injury. Together, these results suggest that mGSCs
may provide a unique source of cardiac stem/progenitor cells for future
regenerative therapy of damaged heart tissue.
PMID- 28410246
TI - Multiple Tumors on the Extremities: Challenge.
PMID- 28410247
TI - CE: Original Research: Creating an Evidence-Based Progression for Clinical
Advancement Programs.
AB - : : Background: The Institute of Medicine (IOM) and the Quality and Safety
Education for Nurses (QSEN) project have identified six nursing competencies and
supported their integration into undergraduate and graduate nursing curricula
nationwide. But integration of those competencies into clinical practice has been
limited, and evidence for the progression of competency proficiency within
clinical advancement programs is scant. Using an evidence-based approach and
building on the competencies identified by the IOM and QSEN, a team of experts at
an academic health system developed eight competency domains and 186 related
knowledge, skills, and attitudes (KSAs) for professional nursing practice.
PURPOSE: The aim of our study was to validate the eight identified competencies
and 186 related KSAs and determine their developmental progression within a
clinical advancement program. METHODS: Using the Delphi technique, nursing
leadership validated the newly identified competency domains and KSAs as
essential to practice. Clinical experts from 13 Magnet-designated hospitals with
clinical advancement programs then participated in Delphi rounds aimed at
reaching consensus on the developmental progression of the 186 KSAs through four
levels of clinical advancement. RESULTS: Two Delphi rounds resulted in consensus
by the expert participants. All eight competency domains were determined to be
essential at all four levels of clinical practice. At the novice level of
practice, the experts identified a greater number of KSAs in the domains of
safety and patient- and family-centered care. At more advanced practice levels,
the experts identified a greater number of KSAs in the domains of
professionalism, teamwork, technology and informatics, and continuous quality
improvement. CONCLUSION: Incorporating the eight competency domains and the 186
KSAs into a framework for clinical advancement programs will likely result in
more clearly defined role expectations; enhance accountability; and elevate and
promote nursing practice, thereby improving clinical outcomes and quality of
care. With their emphasis on quality and safety, the eight competency domains
also offer a framework for enhancing position descriptions, performance
evaluations, clinical recognition, initial and ongoing competency assessment
programs, and orientation and residency programs.
PMID- 28410248
TI - CE: Venous Thromboembolism: Updated Management Guidelines.
AB - : Venous thromboembolism (VTE) is a leading cause of death and disability
worldwide. Each year, more than 10 million cases of VTE are diagnosed; studies
suggest there are as many as 900,000 cases per year in the United States. The
condition is estimated to cost the U.S. health care system between $7 billion and
$10 billion annually. In February 2016, the American College of Chest Physicians
released the 10th edition of the Antithrombotic Therapy for VTE Disease: CHEST
Guideline and Expert Panel Report. After providing an overview of VTE
pathophysiology, risk factors, signs, symptoms, and key clinical assessments,
this article details recommendations from the new guideline, which incorporates
the most up-to-date treatment options for patients with VTE. The authors
highlight key changes from the 2012 guideline, particularly those related to
nursing practice, patient education, care coordination, patient adherence,
medication costs, follow-up appointments, and diagnostic testing.
PMID- 28410249
TI - When could new antiretrovirals be recommended for national treatment programmes
in low-income and middle-income countries: results of a WHO Think Tank.
AB - PURPOSE OF REVIEW: To discuss barriers and opportunities for the introduction of
new antiretrovirals into national treatment programmes in low-income and middle
income countries to support further treatment scale-up. Invitees to a WHO Think
Tank in February 2017 evaluated recently published results. RECENT FINDINGS:
There is not sufficient clinical experience of dolutegravir (DTG), tenofovir
alafenamide (TAF) or efavirenz 400 mg (EFV400) to recommend their use in
pregnancy. Outcomes from births and assessment of congenital anomalies need to be
evaluated from several hundred pregnant women. Clinical experience of these
treatments during rifampicin-based treatment for tuberculosis is also required.
This could be difficult for TAF, which is currently contraindicated with TAF.
Changes in second-line treatment from two nucleoside analogues + protease
inhibitor plus ritonavir will require new randomized trials of alternative
combinations. CONCLUSION: Additional safety and efficacy data on DTG, TAF and
EFV400 in some subpopulations are needed before a large introduction in national
treatment programmes. There is currently limited support for the introduction of
TAF as part of first-line antiretroviral treatment in low-income and middle
income settings. There was an overall agreement for 6-monthly reviews of safety
and efficacy data, in parallel with a phased introduction of the new
antiretrovirals.
PMID- 28410250
TI - Effects of Antigravity Treadmill Training on Gait, Balance, and Fall Risk in
Children With Diplegic Cerebral Palsy.
AB - OBJECTIVE: The aim of this study was to investigate the effects of antigravity
treadmill training on gait, balance, and fall risk in children with diplegic
cerebral palsy. DESIGN: Thirty children with diplegic cerebral palsy were
selected for this randomized controlled study. They were randomly assigned to (1)
an experimental group that received antigravity treadmill training (20 mins/d, 3
d/wk) together with traditional physical therapy for 3 successive mos and (2) a
control group that received only traditional physical therapy program for the
same period. Outcomes included selected gait parameters, postural stability, and
fall risk. Outcomes were measured at baseline and after 3 mos of intervention.
RESULTS: Children in both groups showed significant improvements in the mean
values of all measured variables (P < 0.05), with significantly greater
improvements in the experimental group than the control group. The posttreatment
gait parameters (i.e., velocity, stride length, cadence, and percent of time
spent in double-limb support) were 0.74 m/sec, 119 steps/min, 0.75 m/sec, 0.65
sec, and 55.9% as well as 0.5 m, 125 steps/min, 0.6 m/sec, 0.49 sec, and 50.4%
for the experimental and control group, respectively. CONCLUSIONS: Antigravity
treadmill training may be a useful tool for improving gait parameters, balance,
and fall risk in children with diplegic cerebral palsy.
PMID- 28410251
TI - Association of Need for Tracheotomy With Decreasing Mechanical In-Exsufflation
Flows in Amyotrophic Lateral Sclerosis.
AB - Although patients with lower motor neuron and myopathic disorders can prolong
their lives by depending on continuous noninvasive ventilatory support, most
patients with amyotrophic lateral sclerosis (ALS) cannot and must use
tracheostomy mechanical ventilation to prolong survival. This case demonstrates
that this occurs because amyotrophic lateral sclerosis patients' upper motor
neuron reflex laryngeal closure and stridor cause upper airway collapse that
renders mechanical insufflation-exsufflation (MIE) ineffective in expulsing
airway secretions as well as for permitting continuous noninvasive ventilatory
support. A decrease in MIE-exsufflation flows is a marker for a decrease in upper
airway patency that renders MIE ineffective. As airway secretions accumulate and
baseline oxyhemoglobin saturation decreases, tracheotomy becomes necessary for
further survival. This case demonstrates an association between diminishing MIE
exsufflation flow and need to resort to tracheotomy.
PMID- 28410252
TI - Molecular modifiers of kidney stones.
AB - PURPOSE OF REVIEW: This review discusses the role of molecular modifiers as
inhibitors of kidney stone formation, drawing largely from in-vitro evidence
while also citing relevant in-vivo studies. An emphasis is placed on physical
observations of crystal growth inhibition, including mechanisms of action that
focus predominantly on the literature of calcium oxalate and L-cystine. RECENT
FINDINGS: The last decade has witnessed several breakthroughs in the
identification of molecules with promise to curb kidney stone formation, as well
as discoveries of the mechanisms by which these molecules (or combinations
thereof) function as inhibitors of pathological crystal growth. Studies of L
cystine and calcium oxalate crystallization have uncovered inhibitors that are
more effective than current therapies. In-vitro assays using advanced techniques
such as atomic force microscopy have been able to characterize modifier-crystal
interactions and the mechanisms of crystal growth inhibition. A recent study of
calcium oxalate crystals uncovered a new inhibition pathway leading to crystal
dissolution at relatively low modifier concentrations. SUMMARY: Advanced methods
of identifying therapeutics for kidney stone disease have created a greater
awareness of the potential impact of crystal modifiers in pathological
crystallization. Many natural and synthetic species have the capacity to act as
growth inhibitors; however, the challenge of bridging in-vitro and in-vivo
evidence has proven to be difficult. Future effort to better integrate laboratory
research, clinical trials and animal studies has the potential to broaden our
understanding of crystal growth modification and its role in mitigating
pathological crystallization.
PMID- 28410253
TI - Factors Associated With Visual Field Progression in Cirrus Optical Coherence
Tomography-guided Progression Analysis: A Topographic Approach.
AB - PURPOSE: To identify factors associated with visual field (VF) progression in
optical coherence tomography (OCT)-guided progression analysis (GPA) using a
topographic approach. METHODS: Topographic components of OCT-GPA maps (Cirrus HD
OCT; Carl Zeiss Meditec) were classified according to location (temporal,
superotemporal, superonasal, nasal, inferornasal, and inferotemporal), size
(small, medium, and large), shape (wedge and irregular types), and pattern of
retinal nerve fiber layer (RNFL) progression (widening, deepening, and new
development). All positive findings in OCT-GPA (RNFL thickness maps, profiles,
and average RNFL thickness) were defined as strong RNFL progression. VF
progression was determined by linear regression analysis of VF mean deviation
over time. Univariate and multivariate logistic regression analyses were
performed to evaluate the association of VF progression with OCT-GPA parameters.
RESULTS: In total, 276 primary open-angle glaucoma patients were followed up for
5.1 years. According to OCT-GPA, 89 eyes were found to have RNFL progression. Of
these, VF progression was detected in 27 (30.3%) eyes. Eyes with progressed VF
group showed topographically different characteristics, which were wedge-shaped
(80.6%), large-sized (40.0%), and widening (69.5%) or deepening (11.1%) pattern
of RNFL progression in the inferotemporal (44.4%) and superotemporal (30.6%)
regions, compared with eyes with non-progressed VF group. In multivariate
analysis, strong RNFL progression and widening or deepening pattern of RNFL
progression were significantly associated with VF progression (P=0.012 and 0.016,
respectively). CONCLUSIONS: Topographic analysis in OCT-GPA maps showed different
characteristics between progressed VF and nonprogressed VF groups. Glaucoma
patients with widening or deepening pattern of RNFL progression should be
carefully monitored for greater risk of VF progression.
PMID- 28410254
TI - Decompression Retinopathy After Goniotomy in a Child: A Case Report.
AB - PURPOSE: To report a case of ocular decompression retinopathy that developed in a
child after undergoing goniotomy for uncontrolled pediatric uveitic glaucoma.
PATIENT AND METHODS: We describe an 11-year-old Hispanic boy with a history of
idiopathic uveitis and elevated intraocular pressure (IOP) in both eyes. He
developed marked elevation of the IOP in the right eye (44 mm Hg) despite
glaucoma medical therapy. RESULTS: The patient's right eye was treated with
goniotomy, with reduction of vision to 20/70 and IOP to between 4 and 7 mm Hg
during the first week postoperatively. The retina developed diffuse hemorrhages,
both deep and superficial. Many of these hemorrhages had white centers. The
findings were consistent with decompression retinopathy. The retinal hemorrhages
began to improve 2 weeks and had cleared by 6 weeks after surgery. The IOP
measurements ranged between 14 and 16 mm Hg from 2 to 6 weeks after goniotomy and
the vision returned to preoperative baseline of 20/20-2 in the right eye. Six
weeks after the initial surgery, the left eye was treated with goniotomy with no
complications. CONCLUSIONS: Ocular decompression retinopathy, an uncommon
complication of glaucoma surgery, can occur after goniotomy.
PMID- 28410255
TI - Neurocognitive Correlates of Attention-Deficit Hyperactivity Disorder Symptoms in
Children Born at Extremely Low Gestational Age.
AB - OBJECTIVE: Compared with children born near term, those born extremely preterm
(EP) are at much higher risk for attention-deficit hyperactivity disorder (ADHD).
Little information is available about differences in neuropsychological outcomes
among EP children with and without ADHD. Our analyses aimed to evaluate the
neuropsychological correlates of ADHD symptoms in extremely low gestational age
newborns (ELGANs). METHODS: We obtained Child Symptom Inventory-4 reports from
parents (n = 871) and teachers (n = 634) of 10-year-old children born before the
28th week of gestation. Participants completed standardized assessments of
neurocognitive and academic functioning. RESULTS: In the total sample, children
who screened positive for ADHD symptoms were at increased risk for neurocognitive
limitations. These associations were weaker when the sample was limited to those
with intelligence quotient (IQ) >=70 or >=85. Even those with IQ >=85 who
screened positive for ADHD symptoms were more likely than their peers to have
deficits on the DAS-II Working Memory Cluster and the NEPSY-II Auditory Response
subtest. The risks for impaired academic performance (Z <= -1) on components of
the WIAT-III were 2-to-3 times higher in this group than among ELGANs not
classified as having ADHD symptoms. CONCLUSION: Among children born EP, those
with ADHD symptoms are more likely to have global neurocognitive impairment. When
IQ is within normal limits, ADHD symptoms are associated with deficits in
executive functioning skills. These findings highlight a group at risk for
executive functioning deficits and related academic difficulties, even in the
absence of intellectual disability.
PMID- 28410256
TI - Parent-Reported Severity and Health/Educational Services Use Among US Children
with Autism: Results from a National Survey.
AB - OBJECTIVE: Little national data exist regarding service use patterns for children
with autism spectrum disorder (ASD) of varying severity. This study aimed to
assess the relationship between parent-reported severity and use of educational
and health care services. METHODS: Data from the 2011 Survey of Pathways to
Diagnosis and Services were used to examine a nationally representative sample of
1420 US children aged 6 to 17 years with ASD, with or without developmental delay
and intellectual disability. Weighted multivariable logistic regression assessed
associations of parent-reported ASD severity and child sociodemographic
characteristics with school-based therapy, non-school-based therapy, behavioral
interventions, and specialty provider visits. RESULTS: Higher parent-reported ASD
severity was associated with increased likelihood of current use of school-based
therapy (adjusted odds ratio [AOR] = 4.08, 95% confidence interval =1.85-8.98),
non-school-based therapy (AOR = 3.60 [1.95-6.66]), and behavioral interventions
(AOR = 2.30 [1.22-4.34]), as well as regular specialty provider visits (AOR =
2.99 [1.38-6.46]). Although rates of service use were generally highest among
children with severe ASD, non-school-based therapy and behavioral interventions
were only used by about half of children with severe ASD, and about 1 in 4
children with mild ASD were using none of the therapies asked about. CONCLUSION:
Parent-reported severity is associated with increased therapy and specialty
provider service use among children with ASD. However, substantial variability
exists in service use across levels of severity.
PMID- 28410257
TI - Utilization of a Text and Translation Application for Communication With a
Foreign Deaf Family: A Call for Validation of This Technology-A Case Report.
AB - Effective communication with patients is essential to quality care. Obviously,
language barriers significantly impact this and can increase the risk of poor
patient outcomes. Smartphones and mobile health technology are valuable resources
that are beginning to break down language barriers in health care. We present a
case of a challenging language barrier where successful perioperative
communication was achieved using mobile technology. Although quite beneficial,
use of technology that is not validated exposes providers to unnecessary
medicolegal risk. We hope to highlight the need for validation of such technology
to ensure that these tools are an effective way to accurately communicate with
patients in the perioperative setting.
PMID- 28410258
TI - Behavioral Disturbance Causing Sudden Respiratory Distress in a 3-Year-Old After
Tracheocutaneous Fistula Closure: A Case Report.
AB - A 3-year-old boy underwent tracheostomy at age 5 months for respiratory failure.
The tracheostomy tube was removed a year later but a tracheocutaneous fistula
developed requiring fistulectomy and primary skin closure. After an initial
uneventful course in the postanesthesia care unit, the patient became agitated,
began to scream, and suddenly developed rapidly progressing subcutaneous
emphysema over his chest, face, and abdomen. Orotracheal intubation was
emergently performed and chest radiograph revealed pneumothorax and
pneumomediastinum. The child was taken to the operating room for placement of a
tracheostomy tube.
PMID- 28410259
TI - Central Venous Catheter Placement in the Left Internal Jugular Vein Complicated
by Perforation of the Left Brachiocephalic Vein and Massive Hemothorax: A Case
Report.
AB - An elderly male presented for emergent repair of a ruptured abdominal aortic
aneurysm. For anticipated volume resuscitation, vasopressor administration, and
hemodynamic monitoring, a large-bore central venous catheter was placed in the
left internal jugular vein under ultrasound guidance before surgical incision.
Initially, there were no readily apparent signs of venous perforation. However, a
massive left hemothorax developed because of perforation of the brachiocephalic
vein and violation of the pleural space. This case report discusses both
prevention and management of such a complication.
PMID- 28410260
TI - Intraoperative Tonic-Clonic Seizure Under General Anesthesia Captured by
Electroencephalography: A Case Report.
AB - We present the case of a 34-year-old man undergoing craniotomy for arteriovenous
malformation resection under general anesthesia who suffered a tonic-clonic
seizure captured by intraoperative electroencephalograph. The seizure was
extinguished with a propofol bolus. This patient had no previous history of
seizures, and no precipitating cause was identified. Intraoperative
electroencephalographic seizures under general anesthesia have been recorded
previously in the literature, but our observation is the first to demonstrate
this with overt motor manifestations. We also discuss the differential diagnosis
of an intraoperative seizure under general anesthesia and provide guidance to the
anesthesiologist who encounters this event.
PMID- 28410261
TI - Successful Continuous Adductor Canal Block Placement in a Patient With Absent
Sartorius Muscle: A Case Report.
AB - We report a novel case of a patient who presented for elective total knee
arthroplasty and had distorted adductor canal anatomy due to previous sartorius
rotational flap surgery. Despite the lack of a sartorius muscle on the intended
operative limb, we describe the successful placement of a continuous adductor
canal block. This case is a clinically relevant example that highlights the
importance of the vastoadductor membrane as the anatomical anteromedial boundary
for the adductor canal, and that it remains intact even after sartorius muscle
flap surgery.
PMID- 28410262
TI - Life-Saving Esophageal Intubation in Neonate With Undiagnosed Tracheal Agenesis:
A Case Report.
AB - A 3-day-old, 2.2-kg former 34-week premature infant with imperforate anus
required loop ileostomy surgery. At delivery, the child had respiratory distress.
Endotracheal intubation was "confirmed" by detection of exhaled carbon dioxide
with a Pedi-Cap (Covidien, Dublin, Ireland) and subsequent chest x-ray. On
arrival to the operating room, the pulse oximeter reading was 100% despite a
large leak around the endotracheal tube and high-airway pressures. Packing the
throat reduced the leak and increased the tidal volume. Intraoperative
bronchospasm occurred during the surgery. On postoperative day 1, fiberoptic
examination by an otolaryngologist revealed esophageal intubation and the absence
of laryngeal opening. Subsequent computed tomography scan revealed Floyd type II
tracheal agenesis. To our knowledge, this is the only case of tracheal agenesis
diagnosed after a non-airway related procedure. We discussed how the diagnosis
was missed.
PMID- 28410263
TI - Volatile Sedation in Reversible Cerebral Vasoconstriction Syndrome: A Case
Report.
AB - Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by
reversible multifocal narrowing of cerebral arteries heralded by sudden
(thunderclap) headaches with or without neurological deficits, resolving within 3
months. It often occurs in the peripartum period. To date, the ideal treatment
remains unclear. Here, we report the case of a 31-year-old primigravida who
presented with intracranial hemorrhage and went on to develop RCVS and acute
respiratory distress syndrome over the course of her illness. Her condition was
further complicated by uterine atony and septic shock.We describe for the first
time the use of short-acting volatile sedation for prone positioning in acute
respiratory distress syndrome during RCVS.
PMID- 28410264
TI - Esophageal Atresia/Tracheoesophageal Fistula Repair Complicated by
Tracheomalacia: A Case Report of Successful Management of Respiratory Distress
Using Caudal Morphine.
AB - We report a case of severe respiratory distress in a neonate who was not
endotracheally intubated soon after esophageal atresia/tracheoesophageal fistula
(EA/TEF) repair. In this serious situation, any form of emergency respiratory
support or definitive airway management may compromise the esophageal anastomosis
and fistula repair. The cause of respiratory distress in the early postoperative
period after EA/TEF is multifactorial, and in this case, included symptomatic
tracheomalacia, which is commonly associated with EA/TEF.
PMID- 28410265
TI - Mangiferin inhibits hippocampal NLRP3 inflammasome and exerts antidepressant
effects in a chronic mild stress mice model.
AB - A growing body of evidence suggests that inflammation may contribute toward the
development of major depressive disorder. Mangiferin, a glucosylxanthone from
Mangifera indica, exerts a number of biological actions, including anti
inflammatory effects. Although mangiferin has potential antidepressant activity,
the mechanisms of this effect remain unclear. The present study investigated the
effects of mangiferin on behavioral changes and inflammatory responses induced by
chronic mild stress (CMS) in mice. We found that treatment with mangiferin for 3
weeks significantly increased the body weight of mice and ameliorated CMS-induced
behavioral abnormalities by increasing sucrose consumption, improving locomotor
activities, and decreasing the immobility time in the forced-swimming test and
tail-suspension test. It also suppressed increased serum corticosterone levels in
CMS mice. In response to CMS induction, the NLR family, pyrin domain containing 3
(NLRP3) inflammasome was activated and interleukin (IL)-1beta and IL-18 levels
were increased in the mouse hippocampus. Mangiferin treatment downregulated the
expression of NLRP3, the adaptor protein ASC, and caspase-1, which subsequently
reduced the production of IL-1beta and IL-18 in CMS mice. In sum, our results
indicate that mangiferin exerts antidepressant-like effects in CMS model,
possibly by inhibiting IL-1beta production and NLRP3 inflammasome expression.
PMID- 28410266
TI - 2, 3, 5, 4'-Tetrahydroxystilbene-2-O-beta-D-glucoside prevention of
lipopolysaccharide-induced depressive-like behaviors in mice involves
neuroinflammation and oxido-nitrosative stress inhibition.
AB - Although numerous hypotheses have been raised in recent years, the exact
mechanisms that promote the development of major depression are largely unknown.
Recently, strategies targeting the process of neuroinflammation and oxidative
stress in depression have been attracting greater attention. 2, 3, 5, 4'
Tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), a compound purified from a
traditional Chinese herbal medicine polygonummultiflorum, has been widely
reported to inhibit neuroinflammation and oxidative stress. In this context, we
investigated whether TSG affects lipopolysaccharide (LPS)-induced depressive-like
behaviors in a manner associated with neuroinflammation and oxido-nitrosative
stress. Results showed that administration of ICR mice with 0.83 mg/kg of LPS
induced typical depressive-like behaviors in the experiments of the tail
suspension test, the forced-swimming test, and sucrose preference, and these
behaviors were prevented by TSG treatment (30 and 60 mg/kg). Further analysis
showed that TSG pretreatment at the doses of 30 and 60 mg/kg not only inhibited
the production of proinflammatory cytokines induced by LPS, such as interleukin
1beta, interleukin-6, and tumor necrosis factor-alpha, but also prevented the LPS
induced enhancement of oxido-nitrosative stress in mouse hippocampus and
prefrontal cortex. The LPS-induced decreases in brain-derived neurotrophic factor
levels in the hippocampus and prefrontal cortex were also prevented by TSG
treatment. Generally, our data provide evidence to show that TSG could be used to
cope with depressive-like symptoms by inhibition of neuroinflammation and oxido
nitrosative stress.
PMID- 28410267
TI - Lacrimal Sac Pneumatocele Following Blunt Nasal Trauma.
AB - Pneumatocele of the lacrimal sac is an uncommon entity and has been rarely
reported in literature. The valvular function of the Hasner's valve at the lower
end of nasolacrimal duct is presumed to prevent the retrograde reflux of air into
the lacrimal sac with increased intranasal pressure as in valsalva maneuver. Loss
of this valvular function as noted with persistent positive airway pressure
ventilation can cause retrograde air reflux into lacrimal sac. The authors report
a case of lacrimal sac pneumatocele which developed following blunt nasal trauma
involving the bony nasolacrimal duct.
PMID- 28410268
TI - Long-term anti-itch effect of botulinum neurotoxin A is associated with
downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice.
AB - Itch is a common symptom in patients with skin and systemic diseases, but the
effective treatment is limited. Here, we evaluated the anti-itch effects of the
botulinum toxin type A (BoNT/A) using acute and chronic dry skin itch mouse
models, which were induced by compound 48/80, chloroquine, and a mixture of
acetone-diethylether-water treatment, respectively. Pretreatment of intradermal
BoNT/A exerted long-term inhibitory effects on compound 48/80-induced and
chloroquine-induced acute itch on days 1, 3, 7, and 14, but not on day 21, in
mice. Furthermore, a single injection of BoNT/A reduced the expression of the
transient receptor potential cation channel, subfamily V, member 1 (TRPV1), and
the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) at
both transcriptional and translational levels in the dorsal root ganglia (DRG) in
mice. Pretreatment of BoNT/A also attenuated chronic itch induced by acetone
diethylether-water treatment and abolished the upregulation of TRPA1 in the DRG.
Thus, it was suggested that downregulation of the expression of TRPA1 and TRPV1
in the DRG may contribute toward the long-term anti-itch effects of a single
injection of BoNT/A in mice and BoNT/A treatment may serve as an alternative
strategy for anti-itch therapy.
PMID- 28410269
TI - Social isolation induces schizophrenia-like behavior potentially associated with
HINT1, NMDA receptor 1, and dopamine receptor 2.
AB - Both genetic factors and early life adversity play major roles in the etiology of
schizophrenia. Our previous studies indicated that social isolation (SI) during
early postnatal development leads to several lasting abnormal behavioral and
pathophysiological features resembling the core symptoms of some human
neuropsychiatric disorders in mice. The glutamate and dopamine hypotheses are
tightly linked to the development of schizophrenia. The cross-talk between
glutamate N-methyl-D-aspartate acid receptors and dopamine receptors is
associated with histidine triad nucleotide binding protein 1 (HINT1), which is
correlated with diverse psychiatric disorders. We examined the effects of SI on
schizophrenia-like behavior and used enzyme-linked immunosorbent assays to
investigate the expression levels of HINT1, the NR1 subunit of N-methyl-D
aspartate acid receptor, and dopamine type 2 receptor (D2R) in C57 mice. We found
that SI leads to a series of schizophrenia-related deficits, such as social
withdrawal, anxiety disorder, cognitive impairments, and sensorimotor gating
disturbances. These abnormal phenotypes paralleled changes of HINT1, NR1, and
D2R. SI may be considered a robust model of the effects of early life stress on
the schizophrenia-related behaviors in mice. Potential interactions among HINT1,
NR1, and D2R may underlie the behavioral deficits induced by SI.
PMID- 28410270
TI - The aurora kinase inhibitor AMG 900 increases apoptosis and induces
chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma
cell line.
AB - Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the
current therapy for advanced disease has a limited impact on overall patient
survival. A previous study from our group suggested that elevated expression of
aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar
results were also reported for adult ACTs. The present in-vitro study shows that
AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900
inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary
cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it
potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis
induction and acted synergistically with mitotane and doxorubicin in the
inhibition of proliferation. In addition, we found that AMG 900 activated Notch
signaling and rendered the cells sensitive to the combination of AMG 900 and
Notch signaling inhibition. Altogether, these data show that aurora kinases
inhibition using AMG 900 may be an adjuvant therapy to treat patients with
invasive or recurrent adrenocortical carcinomas.
PMID- 28410271
TI - Measuring the Nursing Work Environment in Mainland China: Further Development of
the Chinese Nursing Work Environment Scale.
AB - BACKGROUND: For the stabilization of the nursing profession in mainland China, a
valid and reliable nursing work environment instrument, grounded in China's
context, should be developed to better provide rigorous evidence for policy
makers. OBJECTIVE: The purpose of the current research was to further develop a
scale that could capture the characteristics of the nursing work environment in
mainland China. METHODS: A convenience sample of 542 nurses employed in a
tertiary hospital of mainland China completed the 108-item Chinese Nursing Work
Environment (C-NWE) Scale (1st ed.). Items that did not differentiate between
respondents with the highest and lowest 27% of total scores and those that did
not meet criteria for factor loadings were set aside. Exploratory factor analysis
based on the maximum likelihood method was used to identify the structure of the
scale. The chi-square test was used to evaluate model fit, and expert review was
conducted to test content validity. Reliability was estimated using Cronbach's
alpha coefficient. RESULTS: The revised C-NWE Scale, which consists of nine
subscales and 47 items, is a simplified version of the C-NWE (1st ed.). Using
exploratory maximum likelihood factor analysis, the normed chi-square fit index
for a nine-factor solution was 1.97. The content validity index for the total
scale was 0.93; Cronbach's alpha was .94. DISCUSSION: Initial evidence of the
psychometric properties of C-NWE scores was presented. Further studies could be
conducted in various settings to identify the C-NWE Scale's validity and
reliability.
PMID- 28410273
TI - Up-regulation of Intracellular Calcium Handling Underlies the Recovery of
Endotoxemic Cardiomyopathy in Mice.
AB - BACKGROUND: In surviving patients, sepsis-induced cardiomyopathy is spontaneously
reversible. In the absence of any experimental data, it is generally thought that
cardiac recovery in sepsis simply follows the remission of systemic inflammation.
Here the authors aimed to identify the myocardial mechanisms underlying cardiac
recovery in endotoxemic mice. METHODS: Male C57BL/6 mice were challenged with
lipopolysaccharide (7 MUg/g, intraperitoneally) and followed for 12 days. The
authors assessed survival, cardiac function by echocardiography, sarcomere
shortening, and calcium transients (with fura-2-acetoxymethyl ester) in
electrically paced cardiomyocytes (5 Hz, 37 degrees C) and myocardial protein
expression by immunoblotting. RESULTS: Left ventricular ejection fraction,
cardiomyocyte sarcomere shortening, and calcium transients were depressed 12 h
after lipopolysaccharide challenge, started to recover by 24 h (day 1), and were
back to baseline at day 3. The recovery of calcium transients at day 3 was
associated with the up-regulation of the sarcoplasmic reticulum calcium pump to
139 +/- 19% (mean +/- SD) of baseline and phospholamban down-regulation to 35 +/-
20% of baseline. At day 6, calcium transients were increased to 123 +/- 31% of
baseline, associated with increased sarcoplasmic reticulum calcium load (to 126
+/- 32% of baseline, as measured with caffeine) and inhibition of sodium/calcium
exchange (to 48 +/- 12% of baseline). CONCLUSIONS: In mice surviving
lipopolysaccharide challenge, the natural recovery of cardiac contractility was
associated with the up-regulation of cardiomyocyte calcium handling above
baseline levels, indicating the presence of an active myocardial recovery
process, which included sarcoplasmic reticulum calcium pump activation, the down
regulation of phospholamban, and sodium/calcium exchange inhibition.
PMID- 28410272
TI - Management of Severe Bleeding in Patients Treated with Direct Oral
Anticoagulants: An Observational Registry Analysis.
AB - BACKGROUND: The use of prothrombin complex concentrates and the role of plasma
concentration of anticoagulants in the management of bleeding in patients treated
with direct oral anticoagulants are still debated. Our aim was to describe
management strategies and outcomes of severe bleeding events in patients treated
with direct oral anticoagulants. METHODS: We performed a prospective cohort study
of 732 patients treated with dabigatran, rivaroxaban, or apixaban hospitalized
for severe bleeding, included prospectively in the registry from June 2013 to
November 2015. RESULTS: Bleeding was gastrointestinal or intracranial in 37% (212
of 732) and 24% (141 of 732) of the cases, respectively. Creatinine clearance was
lower than 60 ml/min in 61% (449 of 732) of the cases. The plasma concentration
of direct oral anticoagulants was determined in 62% (452 of 732) of the cases and
was lower than 50 ng/ml or higher than 400 ng/ml in 9.2% (41 of 452) and in 6.6%
(30 of 452) of the cases, respectively. Activated or nonactivated prothrombin
complex concentrates were administered in 38% of the cases (281 of 732).
Mortality by day 30 was 14% (95% CI, 11 to 16). CONCLUSIONS: Management of severe
bleeding in patients treated with direct oral anticoagulants appears to be
complex. The use of prothrombin complex concentrates differs depending on
bleeding sites and direct oral anticoagulant plasma concentrations. Mortality
differs according to bleeding sites and was similar to previous estimates.
PMID- 28410275
TI - Implementation of an ICU Bundle: An Interprofessional Quality Improvement Project
to Enhance Delirium Management and Monitor Delirium Prevalence in a Single PICU.
AB - OBJECTIVES: To examine the impact of an ICU bundle on delirium screening and
prevalence and describe characteristics of delirium cases. DESIGN: Quality
improvement project with prospective observational analysis. SETTING: Nineteen
bed PICU in an urban academic medical center. PATIENTS: All consecutive patients
admitted from December 1, 2013, to September 30, 2015. INTERVENTIONS: A
multidisciplinary team implemented an ICU bundle consisting of three clinical
protocols: delirium, sedation, and early mobilization using the Plan-Do-Study-Act
cycles as part of a quality improvement project. The delirium protocol
implemented in December 2013 consisted of universal screening with the Cornell
Assessment of Pediatric Delirium revised instrument, prevention and treatment
strategies, and case conferences. The sedation protocol and early mobilization
protocol were implemented in October 2014 and June 2015, respectively.
MEASUREMENTS AND MAIN RESULTS: One thousand eight hundred seventy-five patients
were screened using the Cornell Assessment of Pediatric Delirium revised tool.
One hundred forty patients (17%) had delirium (having Cornell Assessment of
Pediatric Delirium revised scores >= 9 for 48 hr or longer). Seventy-four percent
of delirium positive patients were mechanically ventilated of which 46% were
younger than 12 months and 59% had baseline developmental delays. Forty-one
patients had emerging delirium (having one Cornell Assessment of Pediatric
Delirium revised score >= 9). Statistical process control was used to evaluate
the impact of three ICU bundle process changes on monthly delirium rates over a
22-month period. The delirium rate decreased with the implementation of each
phase of the ICU bundle. Ten months after the delirium protocol was implemented,
the mean delirium rate was 19.3%; after the sedation protocol and early
mobilization protocols were implemented, the mean delirium rate was 11.84%.
CONCLUSIONS: Implementation of an ICU bundle along with staff education and case
conferences is effective for improving delirium screening, detection, and
treatment and is associated with decreased delirium prevalence.
PMID- 28410274
TI - Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis
Induced Multiple Organ Failure Outcome.
AB - OBJECTIVES: We hypothesize that three inflammation pathobiology phenotypes are
associated with increased inflammation, proclivity to develop features of
macrophage activation syndrome, and multiple organ failure-related death in
pediatric severe sepsis. DESIGN: Prospective cohort study comparing children with
severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple
organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin <
200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset
thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase
with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3)
sequential multiple organ failure with hepatobiliary dysfunction (respiratory
distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to
those without any of these phenotypes. SETTING: Tertiary children's hospital
PICU. PATIENTS: One hundred consecutive severe sepsis admissions. INTERVENTIONS:
Clinical data were recorded daily, and blood was collected twice weekly.
MEASUREMENTS AND MAIN RESULTS: Multiple organ failure developed in 75 cases and
eight died. Multiple organ failure cases with any of the three inflammation
phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and
ferritin, p < 0.001) than multiple organ failure cases without any of these
phenotypes (n = 38) or cases with only single organ failure (n = 25). Development
of features of macrophage activation syndrome and death were more common among
multiple organ failure cases with any of the phenotypes (macrophage activation
syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases
without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and
death: 0/38, 0%; p = 0.002). CONCLUSIONS: Our approach to phenotype
categorization remains hypothetical, and the phenotypes identified need to be
confirmed in multicenter studies of pediatric multiple organ dysfunction
syndrome.
PMID- 28410276
TI - HIV Transmission to Premature Very Low Birth Weight Infants.
AB - There is sparse literature about HIV transmission in preterm infants. Eighty-two
HIV-exposed preterm infants received birth polymerase chain reactions (PCRs).
Five (6.1%) were HIV positive with all 5 mothers receiving inadequate
antiretrovirals. Of the PCR-negative infants, 9 died and 87% of the survivors
received further PCR testing which remained negative. With correct care,
intrapartum transmission of HIV can virtually be eliminated.
PMID- 28410277
TI - Use of Population Pharmacokinetics and Electronic Health Records to Assess
Piperacillin-Tazobactam Safety in Infants.
AB - BACKGROUND: Piperacillin, in combination with tazobactam, is frequently used in
infants for treating nosocomial infections, although safety data in this
population are limited. Electronic health record (EHR) data can be used to
evaluate drug safety in infants, but measures of drug exposure are lacking.
METHODS: To relate simulated piperacillin exposure with adverse events (AEs) in
infants using EHR data, we identified infants discharged from 333 neonatal
intensive care units managed by the Pediatrix Medical Group between 1997 and
2012. Using a previously published population pharmacokinetic model in the target
population, we simulated piperacillin steady state area under the concentration
versus time curve from zero to tau (AUCss,0-tau) and steady state maximal drug
concentration (Cmaxss). Next, we used multivariable logistic regression to
evaluate the association between simulated AUCss,0-tau and Cmaxss with clinical
AEs (seizure and rash) and laboratory AEs controlling for gestational age. The
odds ratios (95% confidence intervals) comparing the third versus the first
tertiles for AUCss,0-tau and Cmaxss were reported. RESULTS: We identified 746
infants with a median (interquartile range) gestational age of 30 weeks (26-33)
and postnatal age of 11 days (6-25). The median (interquartile range)
piperacillin dose was 225 mg/kg/d (176-300). No significant associations were
found between simulated piperacillin exposure (AUCss,0-tau and Cmaxss) and
clinical and laboratory AEs. CONCLUSIONS: We found no associations between
predicted piperacillin exposures and the occurrence of AEs. This study confirms
the feasibility of using population pharmacokinetics and EHR to relate drug
exposure with safety.
PMID- 28410279
TI - Ocular Motor Manifestations of Multiple Sclerosis.
AB - BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central
nervous system leading to disability, especially in young patients. Acute or
chronic lesions of MS within the brainstem and the cerebellum frequently result
in ocular motor disorders. EVIDENCE ACQUISITION: This review encompasses the
spectrum of ocular motor disorders in patients with MS emphasizing prevalence,
examination findings, diagnostic features, functional consequences,
classification of MS course, and management of these disturbances of ocular
motility. RESULTS: Ocular motor manifestations of MS can occur acutely in relapse
or chronically, the latter as a consequence of previous relapses or as a chronic
course of the disease. The most frequent and specific acute ocular motor
manifestation is uni- or bilateral internuclear ophthalmoplegia (INO). The most
frequent chronic manifestations include INO and cerebellar ocular motor disorders
such as gaze-evoked nystagmus, saccadic hypermetria, and lack of vestibulo-ocular
reflex inhibition. The most disabling syndrome is pendular nystagmus.
CONCLUSIONS: The high prevalence of ocular motor manifestations emphasizes the
importance of neuro-ophthalmological examination among patients with MS. Because
chronic manifestations may cause minimal or no symptoms, a systematic
investigation of the most common manifestations should be performed in daily
practice. Appropriate treatment may improve visual outcome in some of these
ocular motor disorders.
PMID- 28410278
TI - Neuromyelitis Optica: Deciphering a Complex Immune-Mediated Astrocytopathy.
PMID- 28410280
TI - Long-Term Impacts of Orthokeratology Treatment on Sub-Basal Nerve Plexus and
Corneal Sensitivity Responses and Their Reversibility.
AB - PURPOSE: To examine the effects of one year of overnight orthokeratology (OK)
treatment on the sub-basal nerve plexus (SBNP) and corneal sensitivity and to
assess the reversibility of these effects one month after treatment interruption.
METHODS: Thirty-two subjects with low-moderate myopia underwent OK treatment for
one year. Fifteen non-contact lens wearers served as controls. At the time points
baseline, one year of treatment, and one month after removing the OK lenses, two
tests were conducted: corneal sensitivity (Cochet-Bonnet esthesiometer) and SBNP
imaging by in vivo confocal microscopy. RESULTS: In participants wearing OK
lenses, significant reductions over the year were produced in SBNP nerve density
(P=0.001 and P=0.006) and number of nerves (P<0.001 and P=0.001) in the central
and mid-peripheral cornea, respectively. Differences over the year were also
detected in central objective tortuosity (P=0.002). After lens removal, baseline
values of nerve density (P=0.024 and P=0.001) and number of nerves (P=0.021 and
P<0.001) for the central and mid-peripheral cornea, respectively, were not
recovered. At one month post-treatment, a difference was observed from one-year
values in central corneal sensitivity (P=0.045) and mid-peripheral Langerhans
cell density (P=0.033), and from baseline in mid-peripheral objective tortuosity
(P=0.049). Direct correlation was detected at one year between nerve density and
tortuosity both in the central (P<0.01; r=0.69) and mid-peripheral cornea
(P<0.01; r=0.76). CONCLUSIONS: Long-term OK treatment led to reduced SBNP nerve
density and this was directly correlated with corneal tortuosity. After one month
of treatment interruption, nerve density was still reduced.
PMID- 28410281
TI - Evaluated Conjunctival Blood Flow Velocity in Daily Contact Lens Wearers.
AB - OBJECTIVE: This study examined conjunctival microvasculature development in long
term habitual contact lens (HCL) wearers after a night of sleep. METHODS: Twenty
HCL wearers (15 women and 5 men, aged 28.6+/-6.9 years, mean age+/-standard
deviation) who had worn contact lenses on a daily basis for at least 3 years and
40 noncontact lens (NCL) wearers (23 women and 17 men, aged 36.5+/-6.6 years,
mean age+/-standard deviation) participated in the study. A functional slitlamp
biomicroscopy imaging system was used to image the temporal bulbar conjunctiva.
Imaging was performed in the morning while the contact lens wearers were not
wearing their lenses after a night of sleep. The conjunctival vessel diameters,
blood flow velocities, and flow rates were measured. In addition, fractal
analyses were performed to obtain the vessel network density (Dbox) and
complexity (D0). RESULTS: The average blood flow velocity in HCL wearers after a
night of sleep was 0.59+/-0.19 mm/s, which was significantly higher than that in
NCL wearers (0.48+/-0.17 mm/s, P<0.05). The microvessel network density and
complexity levels (Dbox=1.64+/-0.05 and D0=1.71+/-0.05, respectively) in the HCL
wearers were significantly higher than those in NCL wearers (Dbox=1.61+/-0.05 and
D0=1.69+/-0.04, both P<0.05). The blood flow velocity was positively correlated
with the duration of contact lens wear (r=0.46, P<0.05) and with the daily number
of lens-wearing hours (r=0.49, P<0.05) in HCL wearers. CONCLUSIONS: This study
identified microvascular alterations in the conjunctiva in response to daily
contact lens wear after a night of sleep in long-term daily contact lens wearers.
The unrecovered changes may indicate that para-inflammation occurs on ocular
surfaces because of contact lens wear and that overnight sleeping with no lenses
may not sufficiently restore the ocular surface to an intact state.
PMID- 28410282
TI - New Insights Into the Lipid Layer of the Tear Film and Meibomian Glands.
AB - Meibomian glands secrete lipids (meibum) that form the surface lipid layer of the
tear film and thereby prevent excessive evaporation of tear fluid. Meibomian
gland dysfunction is a major cause of evaporative dry eye, which is more
prevalent than aqueous-deficient dry eye. Noninvasive meibography with infrared
light and an infrared charge-coupled device camera can detect morphological
changes of meibomian glands in both upper and lower eyelids, whereas tear
interferometry allows qualitative and quantitative evaluations of the lipid layer
of the tear film. Such assessment of meibomian gland morphology provides clinical
information that contributes to the diagnosis of evaporative dry eye, whereas
that of the lipid layer of the tear film allows the monitoring of meibomian gland
function. In addition, the balance between the lipid and aqueous layers of the
tear film revealed by tear interferometry has provided both support for the
operation of a compensatory system that maintains tear film homeostasis as well
as insight into the pathophysiology of dry eye.
PMID- 28410283
TI - Postoperative Evaluation of Bilateral Reading Performance With Two Intraocular
Lenses: Twelve-Month Results.
AB - PURPOSE: The aim of this study was to compare the bilateral reading performances
within the first 12 months after the implantation of two intraocular lens (IOL)
models. METHODS: The patients involved in this research had bilateral
phacoemulsification and implantation of the Acriva Reviol MFM 613 IOL (group 1)
or AcrySof ReSTOR SN6AD1 apodized multifocal IOL (group 2). The bilateral reading
performance was evaluated preoperatively and postoperatively using the MNREAD
acuity charts. The reading speed, critical print size, and reading acuity were
measured binocularly at 40 and 60 cm. In addition, the binocular uncorrected
visual acuities (far, UDVA; intermediate, UIVA; and near, UNVA) were also
measured. RESULTS: Each IOL model was implanted in 30 eyes (15 patients), and 30
patients were included in this study. Overall, there were no statistically
significant postoperative differences in the mean UDVA, UIVA and mean (P>0.05).
There were statistically significant postoperative differences in the mean
reading acuity (group 1, 0.07+/-0.10 logMAR; group 2, 0.02+/-0.08 logMAR;
P=0.019) at 40 cm. When tested at 60 cm, the reading acuity (0.13+/-0.10 logMAR
and 0.21+/-0.11 logMAR, respectively; P=0.021) and critical print size (0.25+/
0.13 logMAR and 0.39+/-0.16 logMAR, respectively; P=0.005) were significantly
better in group 1 than in group 2. CONCLUSION: Both of the IOLs achieved good
visual performances. However, the Acriva Reviol MFM 613 IOL performed better than
the AcrySof ReSTOR SN6AD1 at an intermediate distance, whereas the AcrySof ReSTOR
SN6AD1 provided better near distance results.
PMID- 28410284
TI - European Surgical Education and Training in Gynecologic Oncology: The impact of
an Accredited Fellowship.
AB - OBJECTIVE: The aim of this study was to understand the current situation of
surgical education and training in Europe among members of the European Society
of Gynecological Oncology (ESGO) and its impact on the daily surgical practice of
those that have completed an accredited fellowship in gynecologic oncology.
METHODS: A questionnaire addressing topics of interest in surgical training was
designed and sent to ESGO members with surgical experience in gynecologic
oncology. The survey was completely confidentially and could be completed in less
than 5 minutes. Responses from 349 members from 42 European countries were
obtained, which was 38% of the potential target population. The respondents were
divided into 2 groups depending on whether they had undergone an official
accreditation process. RESULTS: Two thirds of respondents said they had received
a good surgical education. However, accredited gynecologists felt that global
surgical training was significantly better. Surgical self-confidence among
accredited specialists was significantly higher regarding most surgical
oncological procedures than it was among their peers without such accreditation.
However, the rate of self-assurance in ultraradical operations, and bowel and
urinary reconstruction was quite low in both groups. There was a general request
for standardizing surgical education across the ESGO area. Respondents demanded
further training in laparoscopy, ultraradical procedures, bowel and urinary
reconstruction, and postoperative management of complications. Furthermore, they
requested the creation of fellowship programs in places where they are not now
accredited and the promotion of rotations and exchange in centers of excellence.
Finally, respondents want supporting training in disadvantaged countries of the
ESGO area. CONCLUSIONS: Specialists in gynecologic oncology that have obtained a
formal accreditation received a significantly better surgical education than
those that have not. The ESGO responders recognize that their society should lead
the standardization of surgical training and promote ways of improving members'
surgical skills.
PMID- 28410285
TI - Comorbidities in Patients With Chronic Obstructive Pulmonary Disease and
Pulmonary Rehabilitation Outcomes.
AB - PURPOSE: The objective of this study was to evaluate the impact of comorbidities
as potential predictors of the response to pulmonary rehabilitation in patients
with chronic obstructive pulmonary disease (COPD). METHODS: The study included
165 patients with COPD with exercise limitations. Comorbidity was classified as
cardiac, metabolic, orthopedic, behavioral health problems, or other diseases.
Number of comorbidities was grouped as 0, 1, or >=2. Outcomes were defined as
improvement in exercise capacity (maximal exercise capacity, 6-minute walk test,
and constant workload cycle exercise duration) and quality of life (Chronic
Respiratory Questionnaire). We assessed the effect of comorbidities on
improvement in outcomes and the impact of the number of comorbidities on the
percentage of patients reaching the minimal clinically important difference for
each outcome. RESULTS: Most patients (n = 160; 96%) were elderly males (mean age
70 years) with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD)
stages II to IV. Sixty-four percent of patients had at least 1 comorbidity. The
>=2 comorbidity group (n = 29) had a higher modified Charlson index and more
patients required continuous supplemental oxygen. Absolute differences in dyspnea
scores in patients with cardiac disease and orthopedic problems compared with
those without these comorbidities were 2.6 +/- 0.87; 95% CI 0.89 to 4.32; p =
.003, and -3.25 +/- 1.23; 95% CI -5.69 to -0.82; p = .009, respectively.
Comorbidities had no significant effect on other exercise outcomes or quality of
life. CONCLUSION: Patients with cardiac disease experienced greater improvement
in the dyspnea score compared with patients with no cardiac disease, whereas
patients with orthopedic problems had a smaller but also clinically significant
improvement in dyspnea after pulmonary rehabilitation.
PMID- 28410286
TI - Successful treatment with imatinib after nilotinib and ipilimumab in a c-kit
mutated advanced melanoma patient: a case report.
AB - Treatment of melanoma remains a challenge in advanced disease. Recently, the
molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated
melanomas led to new treatment strategies. Different trials show that imatinib or
nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There
are little published data on sequential inhibition using these two drugs in
melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit
mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine,
nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor
imatinib. From July 2011 to September 2011, the patient received ipilimumab (four
doses with 3 mg/kg). Clinical assessment after immunotherapy showed disease
progression. Therefore, a treatment change to imatinib 800 mg daily was made from
February 2012 to May 2013. Under this treatment, the patient showed a partial
response as per the RECIST criteria. The present lesions continued responding
(computed tomography scans: May 2012-March 2013). Unfortunately, in October 2012,
new brain metastases developed. Nevertheless, the use of c-kit inhibitors in c
kit-mutated melanoma patients seems to be a promising treatment option.
Furthermore, a delayed response to ipilimumab after 6 months could also have led
to or supported the partial response in this case. However, when two biologically
similar compounds are administered in a melanoma patient and the tumour mass
shows progressive disease upon administration of the first agent, an additional
progression with no effect may be expected when the second one is used. This case
shows, in contrast, that the use of imatinib after progression upon nilotinib can
be beneficial.
PMID- 28410287
TI - Critical points of T1 stage in primary melanoma.
PMID- 28410288
TI - The utility of the combination of a SPECT study with [123I]-FP-CIT of dopamine
transporters and [123I]-MIBG myocardial scintigraphy in differentiating Parkinson
disease from other degenerative parkinsonian syndromes.
AB - OBJECTIVE: Molecular imaging of nigrostriatal dopamine transporters (DAT) and
sympathetic cardiac innervation with single-photon emission computed tomography
(SPECT) are useful tools for differentiating idiopathic Parkinson disease (PD)
from other degenerative parkinsonian syndromes (non-PD). Nevertheless, these
modalities are often insufficient for achieving a definite diagnosis. The aims of
this study were to evaluate the diagnostic accuracy of the combination of these
tools. MATERIALS AND METHODS: The SPECT radiotracers [I]-N-omega-fluoropropyl
2beta-carbomethoxy-3beta-(4-iodophenyl)-nortropane (FP-CIT) and meta-[I]
iodobenzylguanidine (MIBG) were used to research presynaptic dopaminergic
projections (DAT SPECT) and myocardial adrenergic innervation (MIBG
scintigraphy), respectively. PD patients (n=15; age: 61.5+/-13.6 years) and non
PD patients (n=19; age: 62.6+/-14.2 years) who underwent both tests were enrolled
in this study. Receiver-operating characteristic analyses were used to set the
cutoff values of the specific binding ratio in DAT SPECT and the heart to
mediastinum ratio in delayed scan in MIBG scintigraphy for differentiating PD
from non-PD. We calculated the sensitivity, specificity, and test accuracy of the
individual methods and also the combination of these two modalities. RESULTS:
When DAT SPECT and MIBG scintigraphy were used individually, they showed mild
accuracy in differentiating PD from non-PD (DAT, 67.6%; MIBG, 67.6%). The
combination of the two approaches using cutoff values of less than 3.24 for the
specific binding ratio and less than 2.745 for the delayed heart to mediastinum
ratio enabled more accurate differentiation between PD and non-PD. The accuracy
of these indices in distinguishing PD from non-PD was 79.4%. CONCLUSION: These
results suggested that the combination of DAT SPECT and MIBG scintigraphy may
improve the diagnostic accuracy in differentiating PD from non-PD.
PMID- 28410289
TI - Initial experience with real-time hybrid single-photon emission computed
tomography/computed tomography-guided percutaneous transthoracic needle biopsy.
AB - The aim of this study was to explore a technique that uses real-time fusion image
of single-photon emission computed tomography/computed tomography (SPECT/CT) to
guide percutaneous transthoracic needle biopsy (PTNB) and test its feasibility
and safety in patients. Twelve patients with intrathoracic lesions suspicious for
malignancy underwent real-time 99m-technetium sestamibi SPECT/CT-guided PTNB.
Chest SPECT/CT fusion images were used for biopsy planning and intraprocedure
fusion of SPECT with guiding CT was used to adjust the puncture angle and
direction. Tissues were sampled when the tip of needle was placed on the margin
of the hyperactive area within the mass. Postoperation CT scan was performed to
exclude acute complications. The technical success rate, complications, and
histological results were recorded. Room time and operation time were calculated.
All biopsy procedures fulfilled the primary endpoint of yielding diagnostic
results: lung adenocarcinoma (n=5), lung squamous cell carcinoma (n=4), lung
small cell carcinoma (n=1), mediastinum lymphoma (n=1), and pleura inflammation
(n=1). There were no major complications. The mean room time was 74.3+/-10.4
(range: 57-91) min, and the mean operation time was 33.5+/-9.1 (range: 15-45)
min. The average number of CT guiding scans was 3.2 (range: 1-4). The pilot study
explored a new technique of real-time guidance of PTNB using SPECT/CT and
verified its feasibility and safety.
PMID- 28410290
TI - Diagnostic and prognostic impact of fluorine-18-fluorodeoxyglucose PET/CT in
preoperative and postoperative setting of breast cancer patients.
AB - PURPOSE: The aim of this study was to assess the diagnostic and prognostic value
of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in patients with breast cancer
(BC) in the preoperative and the postoperative setting. PATIENTS AND METHODS:
Between 2011 and 2015, we prospectively enrolled 275 patients (mean age: 53
years) with BC (stage I-III; triple-negative or HER2-positive cancer). One
hundred and forty-nine (54.2%) patients underwent F-FDG PET/CT before neoadjuvant
therapy and 126 (45.8%) after surgery and before any additional adjuvant therapy.
The patients were followed for a median period of 44 (2-57) months. The different
effects of PET/CT on the presetting and postsetting phase form a therapeutic and
prognostic point of view were assessed by chi, by Kaplan-Meier, and Cox
regression analyses. RESULTS: In the preoperative setting, PET/CT provided
additional diagnostic information in 42/149 (28%) patients. In particular, 17/70
(24%) patients at stage III were converted into stage IV and 4/68 (6%) at stage
II were upstaged to IV. In the postoperative setting, PET/CT upstaged the disease
in both stage IIIC and stage IV in 14/126 (11%) cases. At the end of follow-up,
28/271 (10%) patients died from BC and 40 (15%) had a recurrence of disease. On
Kaplan-Meier analysis, patients with a positive PET/CT other than the primary
tumor site showed both a worse overall survival and a worse disease-free survival
compared with their counterpart (76 vs. 92%; P=0.063 and 65 vs. 100%; P<0.001).
Conversely, in the postoperative setting, no differences in overall survival and
disease-free survival were found between patients with positive and negative
PET/CT findings (both P>0.05). On multivariate Cox-regression analysis, a
positive PET/CT was a significant predictive factor of a poor prognosis in the
preoperative setting. The significance was lost in the postoperative setting.
CONCLUSION: In the preoperative setting, PET/CT can provide additional diagnostic
and prognostic information. Conversely, in the postoperative setting, PET/CT adds
diagnostic information, but does not provide any adjunctive prognostic
assessment.
PMID- 28410291
TI - Role of Induction Chemotherapy Prior to Chemoradiation in Head and Neck Squamous
Cell Cancer-Systematic Review and Meta-analysis.
AB - The objective of this study was to review and assess the impact of additional
induction chemotherapy to concomitant chemoradiation in head and neck squamous
cell cancer. We performed a comparative systematic review and meta-analysis of
clinical trials of induction chemotherapy + chemoradiation and chemoradiation
alone in this setting. We identified trials randomizing 1314 patients (published
2004-2015). A non-statistically significant trend was observed in favor of
induction chemotherapy + chemoradiation on overall survival (hazard ratio, 0.88;
95% confidence interval, 0.75-1.04). Disease control was superior in the
induction chemotherapy + chemoradiation group (hazard ratio, 0.69; 95% confidence
interval, 0.57-0.83). The rate of complete response improved with induction
chemotherapy compared with concomitant chemoradiation (relative risk, 1.52; 95%
confidence interval, 1.20-1.92). This study showed no benefit of induction
chemotherapy + chemoradiation on overall survival. However, improved complete
response rate and death certificate-only registrations may imply that selected
patients may benefit from induction chemotherapy.
PMID- 28410292
TI - Meta-analyses and Systematic Reviews: Can They Solve Contentious Clinical
Questions?
PMID- 28410293
TI - Long-term Efficacy of Methotrexate Plus Vinblastine/Vinorelbine in a Large Series
of Patients Affected by Desmoid-Type Fibromatosis.
AB - PURPOSE: Today, surgery and radiation therapy have a limited role in desmoid-type
fibromatosis. Different systemic treatments were shown to be effective. Herein,
we report on our institutional experience with low-dose methotrexate (MTX) +
vinca alkaloids in this disease over the last 25 years. METHODS: We
retrospectively reviewed data from all adult patients with sporadic desmoid-type
fibromatosis treated with MTX and vinca alkaloids at our institution between 1989
and 2014. RESULTS: We identified 75 patients treated with MTX + vinblastine
(40%), MTX + vinorelbine (57%), and vinorelbine alone (3%). All patients had
progressive disease before chemotherapy; 72%, 10%, and 48% of patients had
received previous surgery, radiation therapy, and/or systemic treatments,
respectively. Chemotherapy was administered for a median duration of 14 months
and a median number of 37.5 cycles. Eight patients interrupted chemotherapy
because of toxicity. According to RECIST (Response Evaluation Criteria in Solid
Tumors) complete response, partial response, stable disease, and progressive
disease were observed in 1%, 47%, 51%, and 1% of patients, respectively.
Symptomatic relief was obtained in 80% of symptomatic cases. The median
progression-free survival (PFS) was 75 months; it was 136 months in responding
patients. Upon progression, after chemotherapy withdrawal, MTX plus
vinblastine/vinorelbine was offered to 11 patients with partial response, stable
disease, and progressive disease in 4, 6, and 1 cases, resulting in a median PFS
of 53 months. CONCLUSIONS: In this series, chemotherapy with MTX and vinca
alkaloids is confirmed to be active and effective, with a remarkable PFS, higher
in responding patients, and limited toxicity. Even progression can be
successfully rechallenged.
PMID- 28410294
TI - Methotrexate and Vinblastine or Vinorelbine Remain Useful Treatments for Desmoid
Type Fibromatosis 30 Years Later.
PMID- 28410295
TI - From the Guest Editor.
PMID- 28410296
TI - Neoantigen Discovery in Human Cancers.
AB - Cancer is caused by alterations to DNA that ultimately are translated into
altered proteins with unique amino acid sequences when compared with their
counterparts in normal cells. By inference, these altered proteins have the
potential to elicit immune responses such as T-cell recognition, if properly
presented by the immune system following protein degradation and major
histocompatibility complex binding. Historically, identifying tumor-specific
mutant antigens was painstaking work that involved molecular cloning and immune
screening. This scenario has changed dramatically in the last few years as new
sequencing technology combined with computational data analysis can identify the
unique tumor peptide sequences, and algorithmic evaluation of these novel
peptides can estimate their binding affinity to the major histocompatibility
complex haplotypes encoded by each genome. This process can identify unique
neoantigens in each cancer, either as a means of characterizing the overall
neoantigen load or as a precursor to designing a personalized cancer vaccine. An
overview of the data and analysis methods used to identify cancer neoantigens
will be presented along with an in-depth consideration of the nuances of each
step.
PMID- 28410297
TI - Identification of Immunogenic Epitopes by MS/MS.
AB - The interrogation of cell surface-presented immunogenic epitopes is of great
importance to differentiate diseased cells in consequence to malignant
transformation or viral infections. On the basis of this knowledge, next
generation immunotherapies against cancers, autoimmunity, or infectious diseases
can be developed. The identification of altered peptide repertoires of
transformed cells renders mass spectrometry-based analysis indispensable. This is
evident considering the low correlation of gene or protein expression
alterations, respectively, with changes in the peptide repertoire rendering those
analyses less informative. Nevertheless, immunogenicity of peptides appearing to
be exclusively found on diseased cells has to be finally proven in T cell-based
assays. This review highlights the capabilities and limitations of mass
spectrometry in the identification of entire immunopeptidomes, as well as
individual potential immunogenic epitopes with a strong focus on cancer.
Furthermore, an overview of state-of-the-art immunogenicity screens is presented.
PMID- 28410298
TI - Identifying Abundant Immunotherapy and Other Targets in Solid Tumors: Integrating
RNA-seq and Mass Spectrometry Proteomics Data Sets.
AB - RNA-seq and mass-spectrometry proteomics combined with growing data repositories
have greatly increased the capacity to identify candidate proteins or protein
sequence variants that share properties of ideal therapy targets, which include
being abundant in cancer cells, absent or rare in adult organs (especially vital
organs), and shared by many patient tumors. RNA-seq and fixed content arrays can
identify genes that are overexpressed or misexpressed in cancer. RNA-seq is
uniquely suited to identifying cancer-specific sequence variants. We review
factors relevant for determining whether products of genes that are abundant or
differentially abundant in RNA-seq are concordant or discordant with proteins
that are identified as abundant or differentially abundant in mass-spectrometry
proteomics assays.
PMID- 28410302
TI - Tumor-Infiltrating Lymphocyte Therapy and Neoantigens.
AB - The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has
been shown to be effective at mediating tumor regression in more than half of
patients with metastatic melanoma and in mediating long-term complete regression
in approximately one fourth of all patients with this cancer. The success of this
approach in patients with cholangiocarcinoma and colon cancer supports efforts to
expand ACT therapies to treatment of patients bearing a wide array of cancer
types. Recent improvements in deep sequencing of the patient cancers, combined
with extensive immunological testing of autologous tumor-infiltrating
lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous
somatic mutations, termed neoantigens, play important roles in mediating many of
the effective cancer immunotherapies seen in response to ACT.
PMID- 28410300
TI - Applied Cancer Immunogenomics: Leveraging Neoantigen Discovery in Glioblastoma.
AB - Glioblastoma (GBM) remains a significant cause of cancer-related mortality in
pediatric and adult patients with limited treatment options. Immunotherapy
represents a promising new therapeutic approach in many solid and hematologic
malignancies, including GBM, although only a subset of patients responds
clinically. Thus, current efforts are focused on identifying patients most likely
to benefit from immune-based therapies. The cancer immunogenomics approach
identifies candidate neoantigens from genomics information and represents a
potentially exciting new space in precision neuro-oncology. In this review, we
discuss the role of neoantigens in GBM both as predictive biomarkers and as
targets of immunotherapy.
PMID- 28410303
TI - Personalized Therapy: Tumor Antigen Discovery for Adoptive Cellular Therapy.
AB - Adoptive cell therapy using endogenous T cells involves the ex vivo isolation and
expansion of antigen-specific T cells from the peripheral blood and is uniquely
suited for validating and translating antigen discovery. Endogenous T-cell
therapy does not require accessible tumor as a source of infiltrating T cells and
is free of regulatory and logistical constraints associated with engineering T
cells. Candidate epitope peptides identified through antigen discovery may be
rapidly implemented as targets in clinical trials of endogenous T-cell therapy
and even incorporated as an "ad hoc" approach to personalized treatment when
autologous tumor is available. Several first-in-human studies using a uniform
population of antigen-specific T cells defined by phenotype and specificity have
provided a means to confirm candidate antigens as potential tumor rejection
antigens and to evaluate the reasons for success or failure using as a
"transferrable cellular biomarker" the adoptively transferred T cells.
PMID- 28410301
TI - Dendritic Cell Strategies for Eliciting Mutation-Derived Tumor Antigen Responses
in Patients.
AB - Dendritic cells (DCs) are equipped for sensing danger signals and capturing,
processing, and presenting antigens to naive or effector cells and are critical
in inducing humoral and adaptive immunity. Successful vaccinations are those that
activate DCs to elicit both cellular and humoral responses, as well as long
lasting memory response against the target of interest. Recently, it has become
apparent that tumor cells can provide new sources of antigens through
nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds
of mutation-derived tumor antigens (MTAs) or neoantigens. T cells recognizing MTA
have been detected in cancer patients and can even lead to tumor regression.
Designing MTA-specific vaccination strategies will have to take into account the
adjuvant activity of DC subsets and the best formulation to elicit an effective
immune response. We discuss the potential of human DCs to prime MTA-specific
responses.
PMID- 28410299
TI - Antigen Discovery and Therapeutic Targeting in Hematologic Malignancies.
AB - Historically, immune-based therapies have played a leading role in the treatment
of hematologic malignancies, with the efficacy of stem cell transplantation
largely attributable to donor immunity against malignant cells. As new and more
targeted immunotherapies have developed, their role in the treatment of
hematologic malignancies is evolving and expanding. Herein, we discuss approaches
for antigen discovery and review known and novel tumor antigens in hematologic
malignancies. We further explore the role of established and investigational
immunotherapies in hematologic malignancies, with a focus on personalization of
treatment modalities such as cancer vaccines and adoptive cell therapy. Finally,
we identify areas of active investigation and development. Immunotherapy is at an
exciting crossroads for the treatment of hematologic malignancies, with further
investigation aimed at producing effective, targeted immune therapies that
maximize antitumor effects while minimizing toxicity.
PMID- 28410304
TI - Diagnostic rate of primary aldosteronism in Emilia-Romagna, Northern Italy,
during 16 years (2000-2015).
AB - BACKGROUND: Although primary aldosteronism is considered the most common form of
endocrine hypertension, the diagnostic rate of primary aldosteronism in the
territory is unknown. OBJECTIVES: The aims of the current study were to compare
the number of patients discharged with International Classification of Diseases 9
Clinical Modification codes compatible with primary aldosteronism from all the
hospitals in Emilia-Romagna during 16 years (from 2000 to 2015) with the number
of expected cases of primary aldosteronism, and to compare the number of patients
with primary aldosteronism who underwent adrenalectomy in the period 2000-2015
with the number of expected cases of unilateral primary aldosteronism. METHODS:
We accessed the Database of the Emilia-Romagna Health Service to select all
patients from the age of 20 years discharged with International Classification of
Diseases 9 Clinical Modification codes compatible with primary aldosteronism and,
among them, those who underwent adrenalectomy in the same period. The prevalence
of hypertension in Emilia-Romagna from the age of 20 years was drawn from the
Health Search Database. The population from the age of 20 years in Emilia-Romagna
has been drawn from the Italian National Statistical Institute. We hypothesized a
prevalence of primary aldosteronism of 5% among hypertensive patients and a
prevalence of unilateral subtypes of 30% among the primary aldosteronism
patients. RESULTS: A total of 992 patients have been discharged with codes
consistent with primary aldosteronism during 16 years in Emilia-Romagna, that is
1.9% of the expected cases of primary aldosteronism. A total of 160 of them
underwent adrenalectomy in the same period, which corresponds to 1% of the
expected cases of unilateral primary aldosteronism in Emilia-Romagna.
CONCLUSIONS: Our results clearly indicate that primary aldosteronism is
dramatically underdiagnosed and undertreated.
PMID- 28410305
TI - Patient- and Family-Centered Care: First Steps on a Long Journey.
PMID- 28410306
TI - Antibiotics in Sepsis: The New Frontier.
PMID- 28410307
TI - The Decision to Transfuse: One Size Might Not Fit All.
PMID- 28410308
TI - Glucocorticosteroids as Adjunctive Therapy for Acute Respiratory Distress
Syndrome and Sepsis? Yes, But Not as Monotherapy.
PMID- 28410309
TI - Will Artificial Intelligence Contribute to Overuse in Healthcare?
PMID- 28410310
TI - Steroids and beta-Agonists in Acute Respiratory Distress Syndrome: Timing Is
Everything.
PMID- 28410311
TI - Extracorporeal Membrane Oxygenation Therapy for Community-Acquired Pneumonia: Are
We Moving the Dial?
PMID- 28410312
TI - The Obesity Paradox and Effects of Early Nutrition: Is There a Paradox, or Is
There Not?
PMID- 28410313
TI - Driving Pressure-The Emperor's New Clothes.
PMID- 28410314
TI - Times Are Changing in Pediatric Delirium.
PMID- 28410315
TI - beta-Lactams Dosing in Overweight Critically Ill Patients: Are We Driving in the
Dark?
PMID- 28410317
TI - "Defining" Sepsis: Moving Toward Measuring the "Dysregulated Host Response".
PMID- 28410316
TI - Extracorporeal Membrane Oxygenation Support Following Stem Cell Transplant-When
Is All That We Have Still Not Enough?
PMID- 28410319
TI - Interpreting National Databases on Mechanical Circulatory Support.
PMID- 28410320
TI - The authors reply.
PMID- 28410318
TI - Characteristics and Outcome of Patients After Allogeneic Hematopoietic Stem Cell
Transplantation Treated With Extracorporeal Membrane Oxygenation for Acute
Respiratory Distress Syndrome.
AB - OBJECTIVES: The acute respiratory distress syndrome is a frequent condition
following allogeneic hematopoietic stem cell transplantation. Extracorporeal
membrane oxygenation may serve as rescue therapy in refractory acute respiratory
distress syndrome but has not been assessed in allogeneic hematopoietic stem cell
transplantation recipients. DESIGN: Multicenter, retrospective, observational
study. SETTING: ICUs in 12 European tertiary care centers (Austria, Germany,
France, and Belgium). PATIENTS: All allogeneic hematopoietic stem cell
transplantation recipients treated with venovenous extracorporeal membrane
oxygenation for acute respiratory distress syndrome between 2010 and 2015.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven patients, nine
of whom underwent noninvasive ventilation at the time of extracorporeal membrane
oxygenation initiation, were analyzed. ICU admission occurred at a median of 146
(interquartile range, 27-321) days after allogeneic hematopoietic stem cell
transplantation. The main reason for acute respiratory distress syndrome was
pneumonia in 81% of patients. All but one patient undergoing noninvasive
ventilation at extracorporeal membrane oxygenation initiation had to be intubated
thereafter. Overall, seven patients (19%) survived to hospital discharge and were
alive and in remission of their hematologic disease after a follow-up of 18
(range, 5-30) months. Only one of 24 patients (4%) initiated on extracorporeal
membrane oxygenation within 240 days after allogeneic hematopoietic stem cell
transplantation survived compared to six of 13 (46%) of those treated thereafter
(p < 0.01). Fourteen patients (38%) experienced bleeding events, of which six
(16%) were associated with fatal outcomes. CONCLUSIONS: Discouraging survival
rates in patients treated early after allogeneic hematopoietic stem cell
transplantation do not support the use of extracorporeal membrane oxygenation for
acute respiratory distress syndrome in this group. On the contrary, long-term
allogeneic hematopoietic stem cell transplantation recipients otherwise eligible
for full-code ICU management may be potential candidates for extracorporeal
membrane oxygenation therapy in case of severe acute respiratory distress
syndrome failing conventional measures.
PMID- 28410321
TI - Wait! Wait! I Am Not Dead Yet!
PMID- 28410322
TI - The authors reply.
PMID- 28410323
TI - Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute
Liver Failure: Is the Clearance Mechanism Appropriate for Detoxification?
PMID- 28410324
TI - The author replies.
PMID- 28410325
TI - Is the Obesity Paradox Valid in Pediatric Intensive Care?
PMID- 28410326
TI - The authors reply.
PMID- 28410327
TI - The activPALTM Accurately Classifies Activity Intensity Categories in Healthy
Adults.
AB - : The activPAL (AP) monitor is well established for distinguishing sitting,
standing, and stepping time. However, its validity in predicting time in physical
activity intensity categories in a free-living environment has not been
determined. PURPOSE: This study aimed to determine the validity of the AP in
estimating time spent in sedentary, light, and moderate-to-vigorous physical
activity (MVPA) in a free-living environment. METHODS: Thirteen participants
(mean +/- SD age = 24.8 +/- 5.2 yr, BMI = 23.8 +/- 1.9 kg.m) were directly
observed for three 10-h periods wearing an AP. A custom R program was developed
and used to summarize detailed active and sedentary behavior variables from the
AP. AP estimates were compared with direct observation. RESULTS: The AP
accurately and precisely estimated time in activity intensity categories (bias
[95% confidence interval]; sedentary = 0.8 min [-2.9 to 4.5], light = 1.7 min
[2.2-5.7], and -2.6 min [-5.8 to 0.7]). The overall accuracy rate for time in
intensity categories was 96.2%. The AP also accurately estimated guideline
minutes, guideline bouts, prolonged sitting minutes, and prolonged sitting bouts.
CONCLUSION: The AP can be used to accurately capture individualized estimates of
active and sedentary behavior variables in free-living settings.
PMID- 28410328
TI - Manipulation of Muscle Creatine and Glycogen Changes Dual X-ray Absorptiometry
Estimates of Body Composition.
AB - : Standardizing a dual x-ray absorptiometry (DXA) protocol is thought to provide
a reliable measurement of body composition. PURPOSE: We investigated the effects
of manipulating muscle glycogen and creatine content independently and additively
on DXA estimates of lean mass. METHOD: Eighteen well-trained male cyclists
undertook a parallel group application of creatine loading (n = 9) (20 g.d for 5
d loading; 3 g.d maintenance) or placebo (n = 9) with crossover application of
glycogen loading (12 v 6 g.kg BM per day for 48 h) as part of a larger study
involving a glycogen-depleting exercise protocol. Body composition, total body
water, muscle glycogen and creatine content were assessed via DXA, bioelectrical
impedance spectroscopy and standard biopsy techniques. Changes in the mean were
assessed using the following effect-size scale: >0.2 small, >0.6, moderate, >1.2
large and compared with the threshold for the smallest worthwhile effect of the
treatment. RESULTS: Glycogen loading, both with and without creatine loading,
resulted in substantial increases in estimates of lean body mass (mean +/- SD;
3.0% +/- 0.7% and 2.0% +/- 0.9%) and leg lean mass (3.1% +/- 1.8% and 2.6% +/-
1.0%) respectively. A substantial decrease in leg lean mass was observed after
the glycogen depleting condition (-1.4% +/- 1.6%). Total body water showed
substantial increases after glycogen loading (2.3% +/- 2.3%), creatine loading
(1.4% +/- 1.9%) and the combined treatment (2.3% +/- 1.1%). CONCLUSIONS: Changes
in muscle metabolites and water content alter DXA estimates of lean mass during
periods in which minimal change in muscle protein mass is likely. This
information needs to be considered in interpreting the results of DXA-derived
estimates of body composition in athletes.
PMID- 28410329
TI - Psychological Issues Related to Illness and Injury in Athletes and the Team
Physician: A Consensus Statement-2016 Update.
PMID- 28410330
TI - What's New in Shock, May 2017?
PMID- 28410331
TI - The Role of Erbin in GTS-21 Regulating Inflammtory Responses in MDP-Stimulated
Macrophages.
AB - OBJECTIVE: To explore the role of Erbin protein and nucleotide-binding
oligomerization domain 2/receptor-interacting serine/threonine protein kinases
(NOD2/RICK) in GTS-21 activating cholinergic anti-inflammatory pathway. METHODS:
Experiments were randomly divided into four groups: normal control (NC) group,
muramyl dipeptide (MDP) group, 10 MUg/mL MDP, GTS-21 (GTS) group, 10 MUg/mL MDP
plus 50 MUg/mL GTS-21 (alpha7 nAChRs agonist), Erbin shRNA interference (sh
Erbin) group: sh-Erbin RNA plus 10 MUg/mL MDP and 50 MUg/mL GTS-21. We extract
specimens at the point of 1, 6, and 24 h after stimulation of MDP in Raw264.7
macrophages. RESULTS: After stimulation of MDP, the NLR2 mRNA, RICK and Erbin
protein, nuclear factor (NF)-kappaB activity, the pro-inflammatory cytokines
tumor necrosis factor (TNF)-alpha and HMGB1 were significantly increased in MDP
group (P <0.05). The expression peak of TNF-alpha is at 1 h. The peak of HMGB1 is
at 24 h. Compared with MDP group, the NLR2 mRNA, RICK, NF-kappaB, TNF-alpha, and
HMGB1 were significantly decreased, but the Erbin was increased in GTS group (P
<0.05). Compared with GTS group, the NLR2 mRNA, RICK, NF-kappaB, TNF-alpha, and
HMGB1 increase in sh-Erbin group (P <0.05). CONCLUSION: GTS-21 could
significantly inhibit MDP-induced pro-inflammatory cytokines responses via
activating cholinergic anti-inflammatory pathway, and the Erbin might be the key
negative regulatory protein in NLR2/RICK signal transduction.
PMID- 28410332
TI - Sepsis-3 on the Block: What Does It Mean for Preclinical Sepsis Modeling?
AB - To effectively improve outcomes of septic patients, we first need to elucidate
the multifaceted pathogenesis of sepsis syndromes and related inflammatory
conditions. In fulfillment of such needs, in February 2016, new definitions for
sepsis and septic shock were published under the acronym Sepsis-3. Although aimed
at the clinical area, Sepsis-3 will have an inevitable influence upon the field
of translational research as well. Sepsis-3 brings a considerable shift regarding
the experimental focal point: from inflammatory states (SIRS/CARS) to organ
failure (single and multiple) as the decisive factor. This shift exposes several
shortcomings of the current in vivo sepsis modeling including lack of uniform
scoring system for sepsis severity and organ dysfunction/failure; high
variability of organ dysfunction phenotypes among animal species/strains;
difficulty in reproducing severe, intensive care unit grade of organ dysfunction
due to high resistance of experimental animals and others. It is intuitive that
clinical Sepsis-3 should also serve as an incentive for developing a global
standardized approach in sepsis modeling to maximize its translational potential.
This could be achieved, for example, by generating consensus guidelines that
would support scientists in their study design and optimal sepsis modeling
decision-making. An implementation of such hypothetical "Minimum Quality
Threshold in Preclinical Sepsis Studies" guidelines across different species has
a strong potential for making sepsis studies more reliable and transpolatable. We
strongly believe that an internationally coordinated standardization effort in
sepsis modeling will certainly serve the above purposes well.
PMID- 28410333
TI - Perceived Stress, Parent-Adolescent/Young Adult Communication, and Family
Resilience Among Adolescents/Young Adults Who Have a Parent With Cancer in
Taiwan: A Longitudinal Study.
AB - BACKGROUND: Family resilience helps family members successfully overcome
adversity, for example, chronic disease or unpleasant situations. However, few
studies have identified correlates of family resilience among adolescents/young
adults having a parent with cancer. OBJECTIVE: This longitudinal study explored
(1) relationships among family resilience, adolescents' perceived stress, and
parent-adolescent/young adult communication; (2) trends in family resilience with
data collection time; and (3) differences in parent-adolescent/young adult
communication by parent gender (ie, father or mother). METHODS: Participants were
teenagers and young adults (12-25 years) with a parent who had cancer. Data were
collected using structured questionnaires at 3 times for 4 to 5 months, with 2
months between each collection. RESULTS: Of 96 adolescent/young adult
participants enrolled at T1, only 32 completed all measurements at T3. We found
that (1) family resilience was negatively associated with adolescents' perceived
stress (B = -0.35) and positively associated with adolescent/young adult
communication with both the father (B = 0.58) and the mother (B = 0.36), (2) the
degree of family resilience at T3 was significantly lower than at T1 (B = -4.79),
and (3) at all 3 data collection times, the degree of adolescent/young adult
communication was higher with mothers than with fathers, whether the mother had
cancer or did not have cancer. CONCLUSIONS: Family resilience was positively
associated with parent-adolescent/young adult communication and negatively
related to perceived stress. Family resilience tended to decline with longer
parental survival since cancer diagnosis. IMPLICATIONS FOR PRACTICE: We suggest
nursing interventions to reduce adolescent/young adult stress and develop optimal
parent-adolescent/young adult communication to enhance family resilience.
PMID- 28410334
TI - Change of Uncertainty in Illness and Unmet Care Needs in Patients With Recurrent
Hepatocellular Carcinoma During Active Treatment.
AB - BACKGROUND: Uncertainty about or related to cancer-related treatment and
prognosis is commonly experienced by patients with hepatocellular carcinoma and
might be associated with unmet care needs. However, their dynamic associations
have not been examined in this population. OBJECTIVE: The aim of this study was
to explore change in unmet care needs and uncertainty under different levels of
uncertainty (low vs high) before discharge and the significant factors related to
change of uncertainty in patients with recurrent hepatocellular carcinoma after
treatment. METHODS: A set of questionnaires was used to collect data including
symptom distress, supportive care needs, and uncertainty of illness before
discharge (T0), 1 month after discharge (T1), and 2 months after discharge (T2).
The significant factors related to uncertainty were identified by generalized
estimating equations. RESULTS: The patients with high uncertainty, who were
younger in age, had significantly higher levels of symptom distress and unmet
care needs. Before discharge, the patients' highest levels of unmet needs were
psychological in the high-uncertainty group. Patients with jobs, higher unmet
care needs, and high uncertainty before discharge had higher levels of
uncertainty over time. CONCLUSIONS: The changes in uncertainty were significantly
associated with unmet care needs over time, and the baseline level of uncertainty
was a significant factor related to the change of uncertainty. IMPLICATIONS FOR
PRACTICE: Healthcare providers should take into account each individual's age,
levels of psychological need, and symptom distress and should offer personalized
information related to psychological needs and symptom management to decrease
levels of uncertainty before discharge.
PMID- 28410335
TI - Experiences of Oncology and Palliative Care Nurses When Supporting Parents Who
Have Cancer and Dependent Children.
AB - BACKGROUND: It is important not to ignore the impact of parental cancer on
children, and this is where oncology and palliative care nurses can play a key
role, providing support to parents as a regular aspect of oncological nursing
care. OBJECTIVES: This study explored the experience, needs, and confidence of
nurses working in acute cancer services when supporting parents with cancer who
have dependent children. METHODS: Two focus group interviews were conducted with
oncology and palliative care nurses in 1 acute hospital trust in the south of
England. RESULTS: Nurses described how they identified with their patients as a
parent themselves. This identification with patients added to the emotionally
charged context of care and resulted in nurse avoidance of the troubling issue of
dependent children. Nurses identified the importance of peer support with regular
opportunities to reflect on practice when dealing with issues relevant to parents
and children. CONCLUSIONS: Oncology and palliative care nurses take a reactive
approach to family centred care, taking their cue from patients to initiate or
request support for their children. IMPLICATIONS FOR PRACTICE: Guidance was
needed on children's developmental stages and how to communicate with children of
different ages. In addition, guidance was needed on assessing family needs and
access to up to date resources. To enable nurses to engage with the issue of
children, strategies of peer support and further educational opportunities need
to be implemented.
PMID- 28410336
TI - Improved oxygen uptake efficiency slope in acute myocardial infarction patients
after early phase I cardiac rehabilitation.
AB - A predischarge submaximal exercise test is often recommended after acute
myocardial infarction (AMI) as part of phase I cardiac rehabilitation. In this
study, a submaximal exercise parameter, oxygen uptake efficiency slope (OUES),
was used to monitor the benefit of early mobilization within 48 h after AMI. An
early mobilization protocol within 48 h after AMI has been initiated since 1
September 2012 in our center. Patients with onset time of AMI within 1 year
before and 1 year after initiation of the early mobilization protocol were
recruited for comparisons. Sixty patients were analyzed on the basis of this
criterion, and were subjected to predischarge submaximal exercise tests. The OUES
calculated with 100% exercise duration (OUES100) and calculated with the first
50% of exercise duration (OUES50) were obtained and analyzed. Both OUES100 and
OUES50 of the AMI patients with early mobilization were significantly higher than
those without early mobilization (P=0.025 and 0.007, respectively). The OUES100
and OUES50 were also highly correlated (r=0.891, P<0.001). The subgroup analysis
using patients within 3 months before and 3 months after initiation of the
protocol also showed a significant difference. OUES could be used to measure the
exercise capacity and monitor the effect of phase I cardiac rehabilitation in
patients soon after AMI. Early mobilization within 48 h following AMI
significantly enhanced the patient's exercise capacity.
PMID- 28410337
TI - Adaptation of Lean Six Sigma Methodologies for the Evaluation of Veterans Choice
Program at 3 Urban Veterans Affairs Medical Centers.
AB - OBJECTIVE: The Veterans Health Administration (VHA) is adapting to meet the
changing needs of our Veterans. VHA leaders are promoting quality improvement
strategies including Lean Six Sigma (LSS). This study used LSS tools to evaluate
the Veterans Choice Program (VCP), a program that aims to improve access to
health care services for eligible Veterans by expanding health care options to
non-VHA providers. RESEARCH DESIGN: LSS was utilized to assess the current
process and efficiency patterns of the VCP at 3 VHA Medical Centers. LSS
techniques were used to assess data obtained through semistructured interviews
with Veterans, staff, and providers to describe and evaluate the VCP process by
identifying wastes and defects. RESULTS: The LSS methodology facilitated the
process of targeting priorities for improvement and constructing suggestions to
close identified gaps and inefficiencies. Identified key process wastes included
inefficient exchange of clinical information between stakeholders in and outside
of the VHA; poor dissemination of VCP programmatic information; shortages of VCP
participating providers; duplication of appointments; declines in care
coordination; and lack of program adaptability to local processes.
Recommendations for improvement were formulated using LSS. CONCLUSIONS: This
evaluation illustrates how LSS can be utilized to assess a nationally mandated
health care program. By focusing on stakeholder, staff, and Veteran perspectives,
process defects in the VCP were identified and improvement recommendations were
made. However, the current LSS language used is not intuitive in health care and
similar applications of LSS may consider using new language and goals adapted
specifically for health care.
PMID- 28410338
TI - Multiple Sources of Prescription Payment and Risky Opioid Therapy Among Veterans.
AB - BACKGROUND: Opioid overdose and other related harms are a major source of
morbidity and mortality among US Veterans, in part due to high-risk opioid
prescribing. OBJECTIVES: We sought to determine whether having multiple sources
of payment for opioids-as a marker for out-of-system access-is associated with
risky opioid therapy among veterans. RESEARCH DESIGN: Cross-sectional study
examining the association between multiple sources of payment and risky opioid
therapy among all individuals with Veterans Health Administration (VHA) payment
for opioid analgesic prescriptions in Kentucky during fiscal year 2014-2015.
MEASURES: Source of payment categories: (1) VHA only source of payment (sole
source); (2) sources of payment were VHA and at least 1 cash payment [VHA+cash
payment(s)] whether or not there was a third source of payment; and (3) at least
one other noncash source: Medicare, Medicaid, or private insurance [VHA+noncash
source(s)]. Our outcomes were 2 risky opioid therapies: combination
opioid/benzodiazepine therapy and high-dose opioid therapy, defined as morphine
equivalent daily dose >=90 mg. RESULTS: Of the 14,795 individuals in the analytic
sample, there were 81.9% in the sole source category, 6.6% in the VHA+cash
payment(s) category, and 11.5% in the VHA+noncash source(s) category. In logistic
regression, controlling for age and sex, persons with multiple payment sources
had significantly higher odds of each risky opioid therapy, with those in the
VHA+cash having significantly higher odds than those in the VHA+noncash source(s)
group. CONCLUSIONS: Prescribers should examine the prescription monitoring
program as multiple payment sources increase the odds of risky opioid therapy.
PMID- 28410339
TI - Patterns of Buprenorphine-Naloxone Treatment for Opioid Use Disorder in a
Multistate Population.
AB - BACKGROUND: Buprenorphine-naloxone treatment for opioid use disorder has rapidly
expanded, yet little is known about treatment outcomes among patients in the
general population. OBJECTIVE: To examine predictors of treatment duration,
dosage, and continuity in a diverse community setting. RESEARCH DESIGN: We
examined QuintilesIMS Real World Data, an all-payer, pharmacy claims database, to
conduct an analysis of individuals age 18 years and above initiating
buprenorphine-naloxone treatment between January 2010 and July 2012 in 11 states.
We used logistic regression to assess treatment duration longer than 6 months. We
used accelerated failure time models to assess risk of treatment discontinuation.
We used ordinary least squares regression to assess mean daily dosage. For
patients with >=3 fills, we also used logistic regression to assess whether ;an
individual had a medication possession ratio of <80% and/or gaps in treatment >14
days. Models adjusted for individual demographics, prescribing physician
specialty, state, and county-level variables. RESULTS: Overall, 41% of
individuals were retained in treatment for at least 6 months and the mean
treatment length was 266 days. Compared with individuals who paid primarily for
treatment with cash, adjusted odds of 6 month retention were significantly lower
for individuals with primary payment from Medicaid fee-for-service, Medicare part
D, and third-party commercial. There were substantial differences in 6-month
retention across states with the lowest in Arizona and highest in New York. Low
possession ratios occurred for 30% of individuals and 26% experienced treatment
episodes with gaps >14 days. Odds of low-possession and treatment gaps were
largely similar across demographic groups and geographic areas. CONCLUSIONS:
Current initiatives to improve access and quality of buprenorphine-naloxone
treatment should examine geographic barriers as well as the potential role of
insurance benefit design in restricting treatment length.
PMID- 28410341
TI - Effects of Transient and Persistent Anti-drug Antibodies to Certolizumab Pegol:
Longitudinal Data from a 7-Year Study in Crohn's Disease.
AB - BACKGROUND: Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics
and increase the risk of adverse events. A single positive test may not preclude
further treatment because of variations in assays used, test timing, and patient
variables. We evaluated the longitudinal patterns of immunogenicity during 7
years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment
for moderate-to-severe Crohn's disease. METHODS: PRECiSE 3 patients (n = 595)
received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression,
plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal
calprotectin concentrations were measured multiple times. Longitudinal data,
examined for CZP-ADAb positivity and categorized as transient (with temporary/no
effect on CZP concentration), persistent, or negative, were correlated with
clinical and biological variables. RESULTS: Of the CZP-ADAb-positive patients, 40
(22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs.
Demographic characteristics were similar between groups. Median C-reactive
protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma
CZP concentrations were significantly lower (P < 0.0001 at all visits) in the
persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group.
Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma
CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey
Bradshaw Index scores and rates of adverse events were similar among groups.
CONCLUSIONS: This analysis demonstrates that persistent CZP-ADAb has negative
effects on drug levels and efficacy, whereas transient expression may not. Serial
measurements may be needed to characterize ADAb positivity.
www.clinicaltrials.gov, Number NCT00160524.
PMID- 28410340
TI - Inflammatory Bowel Disease is Similar in Patients with Older Onset and Younger
Onset.
AB - BACKGROUND: As the American population is aging, the number of older people with
inflammatory bowel disease is increasing. We used clinical data from the Sinai
Helmsley Alliance for Research Excellence (SHARE), a prospective cohort, to
examine disease and treatment differences in older adults. METHODS: We performed
a cross-sectional study assessing demographics and disease behavior by age at
diagnosis with univariate, bivariate, and multivariate analyses. "Older-onset"
patients were diagnosed after age 60, "younger-onset" patients were diagnosed
before age 60 but are older than 60 years, and the remainder were "young."
RESULTS: There were 91 older-onset, 389 younger-onset, and 3431 young patients
with Crohn's disease. Older-onset patients had more ileal (37%) and colonic (27%)
disease compared with younger-onset and young patients. There were no differences
in disease behavior, location, or surgeries between older-onset and young
patients with Crohn's disease within 5 years of diagnosis. Older-onset patients
with inflammatory disease had a higher odds of being in remission. Young patients
reported more anti-tumor necrosis factor and thiopurine use compared with younger
onset and older-onset patients (P < 0.01). There were 98 older-onset, 218 younger
onset, and 1702 young patients with ulcerative colitis. There were no differences
in disease extent, activity index, or surgeries. Young patients with ulcerative
colitis reported more anti-tumor necrosis factor use (26%) compared with younger
onset patients (17%, P < 0.01). CONCLUSIONS: Disease behavior or location was not
different between younger and older adults with inflammatory bowel disease. Older
patients were less likely to be treated with immunosuppression. If older patients
have similar disease behavior, less frequent treatment with immunosuppressives
may risk suboptimally controlled disease.
PMID- 28410342
TI - Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and
May Predict Need for Surgery.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered body
composition, such as low muscle mass, which affects clinical outcomes. Body
composition changes in overweight patients with IBD are less understood. The
study aim was to determine the prevalence of sarcopenic overweight and obese
patients in a cohort of patients with IBD starting new anti-tumor necrosis factor
alpha therapy and examine differences in response. METHODS: This is a
retrospective review of patients with IBD starting a new anti-tumor necrosis
factor-alpha medication that had computed tomography within 3 months of
initiation. L3 vertebral slice was used for segmentation of body composition and
identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH
vitamin D, and body mass index at anti-tumor necrosis factor-alpha initiation and
at 6 months were collected. Outcomes included hospitalization, need for surgery,
or new biological medication. RESULTS: Ninety patients were studied. Forty-one of
ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index
and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P
< 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did
not predict outcomes in the cohort but was the only significant predictor of need
for surgery in overweight and obese subjects (P = 0.002). CONCLUSIONS: Almost
half of our cohort was sarcopenic. Most of these patients are normal or
overweight and would not be identified as malnourished by traditional measures.
Sarcopenia was a predictor of surgery in patients with a body mass index >= 25.
Identification of sarcopenia has implications for medical nutrition therapy as
typically efforts are focused on underweight patients.
PMID- 28410343
TI - Patient Understanding of the Risks and Benefits of Biologic Therapies in
Inflammatory Bowel Disease: Insights from a Large-scale Analysis of Social Media
Platforms.
AB - BACKGROUND: Few studies have examined inflammatory bowel disease (IBD) patients'
knowledge and understanding of biologic therapies outside traditional surveys.
Here, we used social media data to examine IBD patients' understanding of the
risks and benefits associated with biologic therapies and how this affects
decision-making. METHODS: We collected posts from Twitter and e-forum discussions
from >3000 social media sites posted between June 27, 2012 and June 27, 2015.
Guided by natural language processing, we identified posts with specific IBD
keywords that discussed the risks and/or benefits of biologics. We then manually
coded the resulting posts and performed qualitative analysis using ATLAS.ti
software. A hierarchical coding structure was developed based on the keyword list
and relevant themes were identified through manual coding. RESULTS: We examined
1598 IBD-related posts, of which 452 (28.3%) centered on the risks and/or
benefits of biologics. There were 5 main themes: negative experiences and
concerns with biologics (n = 247; 54.6%), decision-making surrounding biologic
use (n = 169; 37.4%), positive experiences with biologics (n = 168; 37.2%),
information seeking from peers (n = 125; 27.7%), and cost (n = 38; 8.4%). Posts
describing negative experiences primarily commented on side effects from
biologics, concerns about potential side effects and increased cancer risk, and
pregnancy safety concerns. Posts on decision-making focused on nonbiologic
treatment options, hesitation to initiate biologics, and concerns about changing
or discontinuing regimens. CONCLUSIONS: Social media reveals a wide range of
themes governing patients' experience and choice with IBD biologics. The
complexity of navigating their risk-benefit profiles suggests merit in creating
online tailored decision tools to support IBD patients' decision-making with
biologic therapies.
PMID- 28410344
TI - Preoperative Clostridium difficile Infection Does Not Affect Pouch Outcomes in
Patients with Ulcerative Colitis Who Undergo Ileal Pouch-anal Anastomosis.
AB - BACKGROUND: The operation of choice for patients with chronic ulcerative colitis
(CUC) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).
Pouchitis is the most common complication after IPAA. The incidence of
Clostridium difficile infection (CDI) is higher in CUC patients than the general
population and can lead to significant disease flares and higher rates of
colectomy. We sought to determine the risk of pouchitis in patients with
precolectomy CDI and 90-day postoperative IPAA complications. METHODS: A
retrospective case-control study was conducted on patients with CUC who underwent
an IPAA between January 1, 2000 and January 10, 2015. The study cohort was
comprised of patients diagnosed with CDI within 90 days before colectomy;
patients with CUC without CDI comprised the control cohort. The primary outcome
measure was the frequency of pouchitis after IPAA. Secondary outcomes included
time to pouchitis, 90-day postoperative pouch morbidity: surgical site infection,
hemorrhage, anastomotic leak, fistula formation, pouchitis treatment and
response, and pouch failure requiring end-ileostomy or fecal diversion.
Univariate and multivariable analysis was used to determine differences between
CDI and non-CDI groups. RESULTS: Forty-eight case patients and 154 control
patients were included. Patients with preoperative CDI were younger (P = 0.010),
had higher rates of medically refractory disease (P = 0.002), and had greater use
of biologic therapy (P = 0.046). The rate of pouchitis was 50.0% (n = 24) and
46.8% (n = 72) (P = 0.694) among patients with and without preoperative CDI,
respectively. Patients with preoperative CDI who developed pouchitis post-IPAA
were more likely to require medical management with an anti-TNFalpha (P = 0.042)
and surgical management with end/diverting ileostomy (P = 0.042). Preoperative
CDI was associated with higher rates of postoperative IPAA anastamotic or pouch
strictures (P = 0.018). Multivariable analysis revealed primary sclerosing
cholangitis (PSC) as the only variable associated with increased risk for
pouchitis (OR 10.59; 95% CI, 3.07-51.08; P < 0.001). CONCLUSIONS: Preoperative
CDI does not seem to be associated with an increased risk of pouchitis in
patients with CUC.
PMID- 28410345
TI - Development of a Novel Predictive Model for the Clinical Course of Crohn's
Disease: Results from the CONNECT Study.
AB - BACKGROUND: A considerable number of patients with Crohn's disease (CD) develop
irreversible intestinal damage, although the early administration of
immunomodulatory or biological therapies might prevent this. The aims of our
study were to develop and validate a novel predictive model that can be used to
predict the risk of surgical intervention in Korean patients with CD. METHODS:
The prognostic model was derived from the multicenter longitudinal CONNECT
(CrOhn's disease cliNical NEtwork and CohorT) study cohort consisting of 1338
patients with CD, who were split into training and validation sets. The Korean
Crohn's Disease Prediction (KCDP) model was developed with the training set data
using the Cox proportional hazards model and multivariate analysis, and was then
validated using the validation set. RESULTS: A total of 1271 patients with CD
were analyzed. During the follow-up period of 10,188 patient-years (median 7.1
yrs), 361 patients (28.4%) underwent CD-related surgery. Age at diagnosis,
jejunal involvement, initial disease behavior, and perianal disease at diagnosis
were associated with a poor prognosis and included in the KCDP model, which
showed a modest discrimination ability with a Harrel's c-index of 0.731 at 5
years, and was well calibrated (Hosmer-Lemeshow chi = 8.230, P = 0.511).
CONCLUSIONS: This is the first validated surgery risk prediction model for Korean
patients with CD; it provides accurate individualized estimates of the
probability of surgery using clinical parameters collected at diagnosis. This
model might guide appropriate patient selection for the early intensive treatment
of CD.
PMID- 28410346
TI - Improved Survival in a Long-Term Rat Model of Sepsis Is Associated With Reduced
Mitochondrial Calcium Uptake Despite Increased Energetic Demand.
AB - OBJECTIVES: To investigate the relationship between prognosis, changes in
mitochondrial calcium uptake, and bioenergetic status in the heart during sepsis.
DESIGN: In vivo and ex vivo controlled experimental studies. SETTING: University
research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS: Sepsis was
induced by intraperitoneal injection of fecal slurry. Sham-operated animals
served as controls. Confocal microscopy was used to study functional and
bioenergetic parameters in cardiomyocytes isolated after 24-hour sepsis. Electron
microscopy was used to characterize structural changes in mitochondria and
sarcoplasmic reticulum. The functional response to dobutamine was assessed in
vivo by echocardiography. MEASUREMENTS AND MAIN RESULTS: Peak aortic blood flow
velocity measured at 24 hours was a good discriminator for 72-hour survival (area
under the receiver operator characteristic, 0.84 +/- 0.1; p = 0.03) and was used
in ex vivo experiments at 24 hours to identify septic animals with good
prognosis. Measurements from animals with good prognostic showed 1) a smaller
increase in mitochondrial calcium content and in nicotinamide adenine
dinucleotide fluorescence following pacing and 2) increased distance between
mitochondria and sarcoplasmic reticulum on electron microscopy, and 3)
nicotinamide adenine dinucleotide redox potential and adenosine
triphosphate/adenosine diphosphate failed to reach a new steady state following
pacing, suggesting impaired matching of energy supply and demand. In vivo, good
prognosis animals had a blunted response to dobutamine with respect to stroke
volume and kinetic energy. CONCLUSIONS: In situations of higher energetic demand
decreased mitochondrial calcium uptake may constitute an adaptive cellular
response that confers a survival advantage in response to sepsis at a cost of
decreased oxidative capacity.
PMID- 28410347
TI - Accuracy of Zero-Heat-Flux Cutaneous Temperature in Intensive Care Adults.
AB - OBJECTIVES: To compare accuracy of a continuous noninvasive cutaneous temperature
using zero-heat-flux method to esophageal temperature and arterial temperature.
DESIGN: Prospective study. SETTING: ICU and NeuroICU, University Hospital.
PATIENTS: Fifty-two ICU patients over a 4-month period who required continuous
temperature monitoring were included in the study, after informed consent.
INTERVENTIONS: All patients had esophageal temperature probe and a noninvasive
cutaneous device to monitor their core temperature continuously. In seven
patients who required cardiac output monitoring, continuous iliac arterial
temperature was collected. Simultaneous core temperatures were recorded from 1 to
5 days. Comparison to the esophageal temperature, considered as the reference in
this study, used the Bland and Altman method with adjustment for multiple
measurements per patient. MEASUREMENTS AND MAIN RESULTS: The esophageal
temperature ranged from 33 degrees C to 39.7 degrees C, 61,298 pairs of
temperature using zero-heat-flux and esophageal temperature were collected and
1,850 triple of temperature using zero-heat-flux, esophageal temperature, and
arterial temperature. Bias and limits of agreement for temperature using zero
heat-flux were 0.19 degrees C +/- 0.53 degrees C compared with esophageal
temperature with an absolute difference of temperature pairs equal to or lower
than 0.5 degrees C of 92.6% (95% CI, 91.9-93.4%) of cases and equal to or lower
than 1 degrees C for 99.9% (95% CI, 99.7-100.0%) of cases. Compared with arterial
temperature, bias and limits of agreement were -0.00 degrees C +/- 0.36 degrees C
with an absolute difference of temperature pairs equal to or lower than 0.5
degrees C of 99.8% (95% CI, 95.3-100%) of cases. All absolute difference of
temperature pairs between temperature using zero-heat-flux and arterial
temperature and between arterial temperature and esophageal temperature were
equal to or lower than 1 degrees C. No local or systemic serious complication was
observed. CONCLUSIONS: These results suggest a comparable reliability of the
cutaneous sensor using the zero-heat-flux method compared with esophageal or
iliac arterial temperatures measurements.
PMID- 28410349
TI - Zika virus and assisted reproduction.
AB - PURPOSE OF REVIEW: Due to the fact that the Zika virus can be sexually
transmitted, there is a potential risk for disease transmission at several stages
of assisted reproduction. Such a possibility poses a serious challenge to couples
pursing fertility with reproductive technologies. Here, we discuss what is known
regarding Zika virus infection with respect to sexual transmission and correlate
this knowledge with recent recommendations in the realm of infertility treatment.
RECENT FINDINGS: Zika virus can be transmitted from infected men and women
through vaginal, oral or anal intercourse. Zika virus RNA has been detected in
blood, semen, cervical mucus and vaginal fluid. Currently, the Centers for
Disease Control recommends that infected men wait 6 months, and infected women 8
weeks, prior to attempting pregnancy. Reproductive tissue donors should wait 6
months before giving a specimen. SUMMARY: Further study of Zika virus
transmission in different reproductive tissues and establishment of validated
testing methods for viral disease transmissibility are urgently needed.
Reproductive technologists need to establish screening, testing and laboratory
protocols aimed to reduce the risk of Zika virus transmission during assisted
reproduction.
PMID- 28410350
TI - Education, Socioeconomic Status, and Intelligence in Childhood and Stroke Risk in
Later Life: A Meta-analysis.
AB - BACKGROUND: Stroke is the second most common cause of death, and a common cause
of dependency and dementia. Adult vascular risk factors and socioeconomic status
(SES) are associated with increased risk, but less is known about early life risk
factors, such as education, childhood SES, or intelligence (IQ). METHODS: We
comprehensively searched Medline, PsycINFO, and EMBASE from inception to November
2015. We included all studies reporting data on >50 strokes examining
childhood/premorbid IQ, SES, and education. Two reviewers independently screened
full texts and extracted and cross-checked data, including available risk factor
adjustments. We meta-analyzed stroke risk using hazard ratios (HR), odds ratios
(OR), and mean differences (MD). We tested effects of study and participant
characteristics in sensitivity analyses and meta-regression, and assessed
heterogeneity and publication bias. RESULTS: We identified 90 studies examining
stroke risk and education (79), SES (10), or IQ (nine) including approximately
164,683 stroke and over 5 million stroke-free participants. Stroke risk increased
with lower education (OR = 1.35, 95% CI = 1.24, 1.48), SES (OR = 1.28, 95% CI =
1.12, 1.46), and IQ (HR = 1.17, 95% CI = 1.00, 1.37) in studies reporting point
estimates, with similar associations for MD. We found minimal publication bias.
Between-study heterogeneity was partly explained by participant age and case
ascertainment method. CONCLUSIONS: Education, childhood SES, and intelligence
have modest but important associations with lifetime stroke, and hence dementia,
risks. Future studies distinguishing between the individual and combined effects
of education, childhood SES and intelligence are needed to determine the
independent contribution of each factor to stroke risk. See video abstract at,
http://links.lww.com/EDE/B210.
PMID- 28410351
TI - Short article: Viral dynamics among hepatitis C virus chronic infected patients
during direct-acting antiviral agents therapy: impact for monitoring and
optimizing treatment duration.
AB - OBJECTIVES: Direct-acting antiviral agents (DAAs) have provided an ultimate
treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected
patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being
evaluated. Here, the HCV viral dynamics at short times during HCV therapies and
its implications for monitoring and optimizing treatment duration have been
assessed. PATIENTS AND METHODS: HCV chronic infected patients who began HCV
therapy (March 2014 to June 2015) at a reference hospital of the Northwest of
Spain were selected. HCV-RNA was quantified at different short time points during
HCV therapy using Abbott RealTime HCV assay. Epidemiological, clinical, and
virological data were recorded. RESULTS: Eleven HCV-infected patients were
included; 90.9% had cirrhosis (>12.5 kPa) and 72.7% were treatment-experienced.
HCV genotype 1b was the most prevalent (72.7%). All of the combinations were
pegylated interferon-free and all included ribavirin. The median HCV-RNA (log
IU/ml) at baseline was 5.8 (5.4-6.1); the decline between baseline and day 3,
weeks 4, 8, and 12 was 3.2, 4.8, 5.1, and 5.6, respectively. Fewer than 50% of
patients achieved undetectable viral load at weeks 4 and 8; however, all patients
achieved a sustained virologic response at 12 weeks. CONCLUSION: Rapid and high
HCV-RNA decline was observed among HCV-infected patients under DAA-based
regimens, especially for those without cirrhosis. Despite low rates of patients
with undetectable HCV-RNA at weeks 4 and 8, all achieved a sustained virologic
response at 12 weeks. These findings suggest that the time points to monitor HCV
RNA during DAA therapies and the treatment duration need to be optimized.
PMID- 28410352
TI - Small-bowel mucosal healing assessment by capsule endoscopy as a predictor of
long-term clinical remission in patients with Crohn's disease: a systematic
review and meta-analysis.
AB - Capsule endoscopy (CE) may be used for the evaluation and follow-up of patients
with Crohn's disease. CE scores correspond to the degree of mucosal inflammation,
a major therapeutic target. The aim of this meta-analysis and systematic review
was to determine whether mucosal healing assessment by CE may serve as a
predictor of clinical remission in patients with Crohn's disease. To identify
observational or controlled English-language full-text studies assessing mucosal
healing by CE in patients with Crohn's disease up to 30 September 2016, we
searched PubMed, Embase, Central, Medline, and Scopus using the key words
'mucosal healing' and 'capsule endoscopy'. A meta-analysis was carried out using
'Comprehensive meta-analysis' software. Pooled odds ratios and 95% confidence
intervals were calculated. Five observational studies including 142 patients from
five countries fulfilled the inclusion criteria. No publication bias was found by
funnel plot. The mucosal healing CE score was found to be significantly
associated with improved outcome after a follow-up of 12 weeks to 24 months, with
an odds ratio of 11.06 (95% confidence interval: 3.74-32.73, P<0.001). The degree
of heterogeneity among the studies was small (Q=2.014, d.f.[Q]=3, P=0.569 and
I=0). Endoscopy scores may play a role in the long-term prognostic evaluation of
patients with Crohn's disease. Our results may be accepted as proof of concept,
but larger studies are needed to corroborate these findings.
PMID- 28410353
TI - Post-colonoscopy colorectal cancers in Sweden: room for quality improvement.
AB - OBJECTIVE: Post-colonoscopy colorectal cancer (PCCRC), a cancer occurring within
a short interval of a colonoscopy, might be partly explained as missed or
incompletely resected lesions. Associated risk factors are age, sex, comorbidity,
cancer location, and colonoscopy volume. There is a gap in the knowledge of
prevalence of PCCRC and the impact of different risk factors in Sweden. METHODS:
This is a retrospective population-based observational cohort study of the
colonoscopies performed on adults during the years 2001-2010 that were identified
from Swedish health registers. The rate of PCCRC (diagnosed 6-36 months after the
first colonoscopy) was defined as the number of PCCRCs divided by the number of
colorectal cancers (CRC) in the interval of 0-36 months. Univariate and
multivariate Poisson regression analyses examined associations with PCCRC.
RESULTS: There were 289 729 colonoscopies performed on 249 079 individuals
included in the study. There were 16 319 individuals with a colorectal cancer
diagnosis 0-36 months after a colonoscopy. Of these, 1286 (7.9%) were PCCRCs. In
the multivariate analysis, young age (18-30 years) and former polyp diagnosis had
the highest risks [relative risk (RR)=3.3; 95% confidence interval: 2.1-5.2 and
RR=3.1; 95% confidence interval: 2.7-3.6]. The impact of other risk factors, such
as female sex, comorbidity, right sided colorectal cancer location, and time
period, was consistent with the finding in other studies. CONCLUSION: The
prevalence of PCCRC in Sweden seems to be relatively high, indicating that there
is room for improvement in colonoscopy quality. The high RR of PCCRC in the
youngest age group, even though there were only a few cases, has not been
described in other studies.
PMID- 28410354
TI - Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film
Instability After Corneal Refractive Surgery.
AB - PURPOSE: To investigate associations between changes in tear film instability and
the lipid layer thickness (LLT) and blink pattern after corneal refractive
surgery (CRS). METHODS: Forty patients were enrolled in this study. The LLT and
blink pattern were evaluated 1 week before and 30 days after CRS using a novel
interferometer and an ocular surface disease index (OSDI) questionnaire, and
other tear film stability markers were also evaluated. RESULTS: Mean OSDI scores
increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores
increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time
(NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average
noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds
(P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20
seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not
change significantly (P = 0.447). The change in NIBUT-Ave was positively
correlated with that in LLT (P = 0.003) and negatively correlated with that in
the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT,
LLT, and blink pattern were not different between the laser-assisted in situ
keratomileusis and laser-assisted subepithelial keratomileusis groups.
CONCLUSIONS: A decrease in tear film stability occurs 1 month after CRS, the
change in the blink pattern and unchanged LLT preoperatively and postoperatively
suggesting that these parameters play a role in maintaining tear film stability
after CRS.
PMID- 28410355
TI - Descemetorhexis Without Graft Placement for the Treatment of Fuchs Endothelial
Dystrophy: Preliminary Results and Review of the Literature.
AB - PURPOSE: To report our preliminary experience with a central descemetorhexis
without graft placement in Fuchs endothelial corneal dystrophy (FECD) and to
review the existing literature on the topic. METHODS: A 4-mm central
descemetorhexis was performed in 5 patients (4 women, 1 man; mean age: 69.8 +/-
8.6 yrs; range: 57-78 yrs) with FECD. All patients had central confluent guttae,
undetectable central endothelial cell count, healthy peripheral corneal
endothelium, no clinically evident bullous keratopathy, and no ocular
comorbidities. In 3 patients, the procedure was combined with phacoemulsification
and intraocular lens implantation. RESULTS: All patients completed at least 6
months of postoperative follow-up (mean follow-up 9 +/- 2.5 mo; 7-13 mo).
Endothelial repopulation of the central stroma was completed in all patients by
the third month. Corneal clarity was achieved in 4 of 5 patients. The patient
with persistent edema and haze had the highest preoperative central pachymetry. A
final improvement in corrected visual acuity was achieved in 4/5 patients. A
reduction in preoperative central pachymetry was observed in all cases. All
patients developed deep stromal opacities around the margin of the
descemetorhexis, which did not resolve over the follow-up time. Abnormal corneal
topography and irregular astigmatism developed in 3 of 5 patients; these patients
achieved 20/20 corrected distance visual acuity with rigid gas-permeable contact
lens fitting. CONCLUSIONS: In partial concordance with previous studies,
preliminary outcomes of a central descemetorhexis in FECD performed without
endothelial graft placement seemed rather unpredictable. Baring of central stroma
may trigger a variable wound-healing response with subsequent posterior stromal
scarring and topographical irregularity.
PMID- 28410356
TI - Water Exposure is a Common Risk Behavior Among Soft and Gas-Permeable Contact
Lens Wearers.
AB - PURPOSE: To understand soft contact lens (SCL) and gas-permeable (GP) lens
wearers' behaviors and knowledge regarding exposure of lenses to water. METHODS:
The Contact Lens Risk Survey (CLRS) and health behavior questions were completed
online by a convenience sample of 1056 SCL and 85 GP lens wearers aged 20 to 76
years. Participants were asked about exposing their lenses to water and their
understanding of risks associated with these behaviors. Chi-square analyses
examined relationships between patient behaviors and perceptions. RESULTS: GP
lens wearers were more likely than SCL wearers to ever rinse or store lenses in
water (rinsing: 91% GP, 31% SCL, P < 0.001; storing: 33% GP, 15% SCL P < 0.001).
Among SCL wearers, men were more likely to store (24% vs. 13%, P = 0.003) or
rinse (41% vs. 29%, P = 0.012) their lenses in water. Showering while wearing
lenses was more common in SCL wearers (86%) than GP lens wearers (67%) (P <
0.0001). Swimming while wearing lenses was reported by 62% of SCL wearers and 48%
of GP lens wearers (P = 0.027). Wearers who rinsed (SCL; P < 0.0001, GP; P =
0.11) or stored lenses in water (SCL; P < 0.0001, GP P = 0.007) reported that
this behavior had little or no effect on their infection risk, compared with
those who did not. Both SCL (P < 0.0001) and GP lens wearers (P < 0.0001)
perceived that distilled water was safer than tap water for storing or rinsing
lenses. CONCLUSIONS: Despite previously published evidence of Acanthamoeba
keratitis' association with water exposure, most SCL, and nearly all GP lens
wearers, regularly expose their lenses to water, with many unaware of the risk.
PMID- 28410357
TI - Donor Endothelial Cell Count Does Not Correlate With Descemet Stripping Automated
Endothelial Keratoplasty Transplant Survival After 2 Years of Follow-up.
AB - PURPOSE: To analyze the influence of low endothelial cell density (ECD) of donor
cornea tissue, donor age, and sex on the transplant survival rate after Descemet
stripping automated endothelial keratoplasty (DSAEK). METHODS: Graft ECD, age,
and sex of donors used for DSAEK (n = 1789) during 7 years (2007-2014) in 4
Scandinavian hospitals were assessed for potential association with transplant
survival at 2 years of follow-up using a Cox regression model correcting for
confounding factors. The data were obtained from The Swedish Cornea Transplant
Registry. RESULTS: Transplant failure occurred in 196 patients, with 69 early
failures during the first 3 postoperative months, and 127 late secondary
failures. Twenty-five of the late secondary failures were due to rejection.
Reversible rejections occurred in 67 patients. There was no significant impact of
donor age [hazard ratio (HR) 1.0, 95% confidence interval (CI), 0.99-1.02, P =
0.32] or endothelial cell count (HR 1.00, 95% CI, 0.99-1.01, P = 0.3) on the
survival rate of DSAEK transplants at 2 years of follow-up. The use of donor
grafts with low ECD (<2300 cells/mm) did not influence the survival rate (HR 1.3,
95% CI, 0.76-2.35, P = 0.31). Male donor sex was associated with lower 2-year
graft survival (HR 1.5, 95% CI, 1.04-2.28, P = 0.03), but not with rejection
events (P = 0.26). CONCLUSIONS: Based on data from The Swedish Cornea Transplant
Registry, low donor ECD was not detrimental to graft survival, whereas donor sex
seemed to influence the outcome at the end of the 2-year follow-up.
PMID- 28410358
TI - Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster
Vaccination.
AB - PURPOSE: We present a case of reactivated herpes zoster keratouveitis of 6 years
duration with corneal perforation requiring penetrating keratoplasty shortly
after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada).
METHODS: Retrospective case report. RESULTS: A 67-year-old woman with a 5-year
history of recurrent unilateral herpes zoster keratouveitis in her right eye
presented with another recurrence 2 weeks after Zostavax vaccination. Three
months later, she developed descemetocele and 2 months afterward, corneal
perforation, which was managed by penetrating keratoplasty.
Immunohistopathological examination disclosed positive staining for varicella
zoster virus in most of the keratocytes adjacent to the descemetocele and
perforation, most vividly in the deeper two-thirds of the stroma where the
keratocytes were most dense, but not in corneal epithelium or endothelium.
Electron microscopic examination showed universally severely degenerated corneal
keratocytes in the corneal stroma adjacent to the perforation with variable
numbers of herpes virus capsids present in half of these cells. Only a rare
normal-appearing keratocyte was identified in the more peripheral corneal stroma.
CONCLUSIONS: We present a case of reactivation of herpes keratouveitis shortly
after vaccination with Zostavax in a patient with previous herpes zoster
ophthalmicus. We demonstrate, for the first time, ultrastructural evidence
consistent with inactive virus capsids in diffusely degenerated keratocytes in
the extracted corneal tissue.
PMID- 28410359
TI - Intraoperative S-Stamp Enabled Rescue of 3 Inverted Descemet Membrane Endothelial
Keratoplasty Grafts.
AB - PURPOSE: To report the clinical outcomes of 3 Descemet membrane endothelial
keratoplasty (DMEK) grafts, in which an upside down DMEK graft orientation was
discovered after SF6 gas insufflation of the anterior chamber and the orientation
was then corrected intraoperatively. METHODS: A total of 371 consecutive DMEK
cases using an S-stamp were analyzed and found to include 3 cases in which the
DMEK graft was initially elevated with SF6 gas in an upside down orientation, as
demonstrated intraoperatively by the S-stamp. In each case, the graft was
immediately manipulated into the proper orientation and the rescued case
completed using our standard technique. The postoperative complications of these
cases were reported and the percentage of endothelial cell loss at 6 months was
compared with that of cases in this series without this rare intraoperative
complication. RESULTS: All 3 rescued grafts achieved successful recipient corneal
clearance and improved vision for the patient. There was no graft failure,
rebubble, or rejection in these 3 cases. The average 6-month endothelial cell
loss in the 3 initially inverted grafts was 51%, 58.3%, and 67% compared with
31.6% (SD +/- 17.4%) in the series at large. CONCLUSIONS: Incorporation of a
stromal-sided S-stamp has been previously shown to reduce the risk of iatrogenic
primary graft failure through the prevention of upside down graft implantation.
In these 3 instances, although the stamp did not prevent initial upside down
graft elevation, it did allow the surgeon to immediately recognize this rare
problem, correct it intraoperatively, and prevent iatrogenic graft failure in
each case.
PMID- 28410360
TI - Estimation of Prevalence of Meibomian Gland Dysfunction in Japan.
AB - PURPOSE: To estimate the prevalence of meibomian gland dysfunction (MGD) in the
Japanese population using new diagnostic criteria, including lid margin
abnormalities and signs of occlusion of the meibomian gland orifices as essential
signs. METHODS: The participants were consecutive patients scheduled for cataract
surgery at Inouye Eye Hospital. All participants were aged 50 years or older. The
participants completed a symptoms questionnaire and underwent a comprehensive
slit-lamp examination. MGD was diagnosed when both of the following 2 factors
were positive: lid margin abnormalities and signs of occlusion of the meibomian
gland orifices. RESULTS: The study included 510 participants (205 men, 305 women)
of mean age 71.1 +/- 8.5 (range 50-93) years. The prevalence rates of symptomatic
MGD and total (symptomatic + asymptomatic) MGD were 18.0% and 47.5%,
respectively. The prevalence of total MGD increased significantly with increasing
patient age (P < 0.0001). The ratio of men to women and the prevalence of
systemic disease did not differ between participants who were positive or
negative for MGD. For the total MGD group, slit-lamp findings (lid margin
abnormality, shift of the mucocutaneous junction, telangiectasia, and plugging)
were more frequent; tear film breakup time was shorter; and the meiboscore was
higher than in participants without MGD. CONCLUSIONS: The prevalence of MGD is
high in the Japanese population aged 50 years or older.
PMID- 28410361
TI - Rates of Intraocular Pressure Elevation and Use of Topical Antihypertensive
Medication After Descemet Stripping Automated Endothelial Keratoplasty.
AB - PURPOSE: To investigate intraocular pressure (IOP) elevation and medication
augmentation after Descemet stripping automated endothelial keratoplasty (DSAEK)
in those with and without glaucoma. METHODS: The records of 379 patients who
underwent DSAEK at the Cleveland Clinic Foundation between January 2009 and 2014
were retrospectively reviewed. Postoperative IOP elevations were considered
significant if IOP was >=22 mm Hg on at least 1 follow-up visit or if it
increased by >=10 mm Hg from baseline. RESULTS: The incidence rate of IOP
elevation was 4% per person-month (confidence interval [CI], 3%-6%) in patients
with preexisting glaucoma and 3% (CI, 2%-4%) in those without. Rates of
medication augmentation were 4% per person-month (CI, 3%-5%) in patients with
glaucoma and 1.8% (CI, 1.4%-2.4%) in those without. Incidence rates for both
outcomes peaked at 1 month. Whites had nearly a 47% lower incidence of IOP
elevation compared with nonwhites (P = 0.004); patients with pseudophakic bullous
keratopathy had a 54% higher incidence of IOP elevation (P = 0.024); and those
with Fuchs endothelial corneal dystrophy had a 36% lower incidence (P = 0.024).
Patients with glaucoma had over a 2-fold higher incidence of medication
augmentation compared with those without (hazard rate ratio = 2.08, P < 0.001).
CONCLUSIONS: The incidence of post-DSAEK IOP elevation did not significantly
differ by glaucoma status, although patients with glaucoma were more likely to
have escalation of topical antihypertensive therapy. The incidence of IOP
elevation was significantly associated with pseudophakic bullous keratopathy and
nonwhite race. These patients should be followed closely in the early
postoperative period, as elevated IOP can be a serious consequence of DSAEK.
PMID- 28410362
TI - Joint Assessment of Donor and Recipient hTERT Gene Polymorphism Provides
Additional Information for Early Kidney Transplantation Outcomes.
AB - BACKGROUND There are several genes and genetic loci affecting telomere length,
including hTERT gene and BICD1 gene as well as polymorphisms within chromosome
18. It has been demonstrated that the age of the donor is a negative factor
associated with long-term kidney allograft function, and that post-transplant
complications accelerate transplanted organ aging, thus contributing to estimated
glomerular filtration rate (eGFR) decreases. The aim of this study was a joint
assessment of donors' and recipients' hTERT and BICD1 genes as well as chromosome
18 polymorphisms with regard to early kidney transplantation outcomes. MATERIAL
AND METHODS The study enrolled 74 pairs of Polish Caucasian kidney allograft
cadaveric donors (60% male, mean age 45.99+/-14.62) and recipients (50.0% male,
mean age 48.89+/-13.50). The transplantation procedure (Tx) was performed between
2001 and 2012. All samples were genotyped in duplicate using Real-Time PCR.
RESULTS This study showed that rs2735940 hTERT CX-TT donor-recipient genotype
pair was associated with almost five times higher odds (OR=4.82; 95% CI: 1.32-18;
p=0.016) of delayed graft function (DGF), and that rs2735940 hTERT, rs2630578
BICD1, and rs7235755 chromosome 18 polymorphisms combined pairs were not
associated with acute rejection (AR). CONCLUSIONS In conclusion, both the donor's
and the recipient's rs2735940 hTERT gene polymorphism was associated with early
graft function after transplantation. The odds of DGF were almost five times
higher for a combination of CX (CT or CC) donor genotype and TT recipient
genotype. Joint assessment of donor-recipient genotype pairs provides more
information for prediction of early kidney transplantation outcomes.
PMID- 28410363
TI - Highly accessible AU-rich regions in 3' untranslated regions are hotspots for
binding of regulatory factors.
AB - Post-transcriptional regulation is regarded as one of the major processes
involved in the regulation of gene expression. It is mainly performed by RNA
binding proteins and microRNAs, which target RNAs and typically affect their
stability. Recent efforts from the scientific community have aimed at
understanding post-transcriptional regulation at a global scale by using high
throughput sequencing techniques such as cross-linking and immunoprecipitation
(CLIP), which facilitates identification of binding sites of these regulatory
factors. However, the diversity in the experimental procedures and bioinformatics
analyses has hindered the integration of multiple datasets and thus limited the
development of an integrated view of post-transcriptional regulation. In this
work, we have performed a comprehensive analysis of 107 CLIP datasets from 49
different RBPs in HEK293 cells to shed light on the complex interactions that
govern post-transcriptional regulation. By developing a more stringent CLIP
analysis pipeline we have discovered the existence of conserved regulatory AU
rich regions in the 3'UTRs where miRNAs and RBPs that regulate several processes
such as polyadenylation or mRNA stability bind. Analogous to promoters, many
factors have binding sites overlapping or in close proximity in these hotspots
and hence the regulation of the mRNA may depend on their relative concentrations.
This hypothesis is supported by RBP knockdown experiments that alter the relative
concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts
containing "free" target sites show increased expression levels compared to those
containing target sites in hotspots, which suggests that target sites within
hotspots are less available for miRNAs to bind. Interestingly, these hotspots
appear enriched in genes with regulatory functions such as DNA binding and RNA
binding. Taken together, our results suggest that hotspots are functional
regulatory elements that define an extra layer of regulation of post
transcriptional regulatory networks.
PMID- 28410365
TI - Effects of physical education, extracurricular sports activities, and leisure
satisfaction on adolescent aggressive behavior: A latent growth modeling
approach.
AB - The present study aimed to investigate the longitudinal influence of physical
education classes, extracurricular sports activities, and leisure satisfaction on
aggressive behavior among South Korean adolescents. Data were drawn from the
Korea Youth Panel Survey. We used latent growth curve modeling to explain the
growth trajectory of adolescent aggressive behaviors and a multi-group analysis
to investigate gender differences in aggressive behavior. The results indicated
that adolescents' aggressive behavior significantly changed with age. There were
significant gender-based differences in the level of and changes in aggressive
behavior over time. Both extracurricular sports activities and leisure
satisfaction had significant influences on the changes in adolescents' aggressive
behavior with age, whereas physical education classes did not.
PMID- 28410364
TI - Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic
kidney disease or retinal degeneration.
AB - Arf4 is proposed to be a critical regulator of membrane protein trafficking in
early secretory pathway. More recently, Arf4 was also implicated in regulating
ciliary trafficking, however, this has not been comprehensively tested in vivo.
To directly address Arf4's role in ciliary transport, we deleted Arf4
specifically in either rod photoreceptor cells, kidney, or globally during the
early postnatal period. Arf4 deletion in photoreceptors did not cause protein
mislocalization or retinal degeneration, as expected if Arf4 played a role in
protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney
did not cause cystic disease, as expected if Arf4 were involved in general
ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal
period resulted in growth restriction, severe pancreatic degeneration and early
death. These findings are consistent with Arf4 playing a critical role in
endomembrane trafficking, particularly in the pancreas, but not in ciliary
function.
PMID- 28410366
TI - Brief educational interventions to improve performance on novel quality metrics
in ambulatory settings in Kenya: A multi-site pre-post effectiveness trial.
AB - BACKGROUND: The quality of primary care delivered in resource-limited settings is
low. While some progress has been made using educational interventions, it is not
yet clear how to sustainably improve care for common acute illnesses in the
outpatient setting. Management of urinary tract infection is particularly
important in resource-limited settings, where it is commonly diagnosed and
associated with high levels of antimicrobial resistance. We describe an
educational programme targeting non-physician health care providers and its
effects on various clinical quality metrics for urinary tract infection. METHODS:
We used a series of educational interventions including 1) formal introduction of
a clinical practice guideline, 2) peer-to-peer chart review, and 3) peer-reviewed
literature describing local antimicrobial resistance patterns. Interventions were
conducted for clinical officers (N = 24) at two outpatient centers near Nairobi,
Kenya over a one-year period. The medical records of 474 patients with urinary
tract infections were scored on five clinical quality metrics, with the primary
outcome being the proportion of cases in which the guideline-recommended
antibiotic was prescribed. The results at baseline and following each
intervention were compared using chi-squared tests and unpaired two-tailed T
tests for significance. Logistic regression analysis was used to assess for
possible confounders. FINDINGS: Clinician adherence to the guideline-recommended
antibiotic improved significantly during the study period, from 19% at baseline
to 68% following all interventions (Chi2 = 150.7, p < 0.001). The secondary
outcome of composite quality score also improved significantly from an average of
2.16 to 3.00 on a five-point scale (t = 6.58, p < 0.001). Interventions had
different effects at different clinical sites; the primary outcome of appropriate
antibiotic prescription was met 83% of the time at Penda Health, and 50% of the
time at AICKH, possibly reflecting differences in onboarding and management of
clinical officers. Logistic regression analysis showed that intervention stage
and clinical site were independent predictors of the primary outcome (p <
0.0001), while all other features, including provider and patient age, were not
significant at a conservative threshold of p < 0.05. CONCLUSION: This study shows
that brief educational interventions can dramatically improve the quality of care
for routine acute illnesses in the outpatient setting. Measurement of quality
metrics allows for further targeting of educational interventions depending on
the needs of the providers and the community. Further study is needed to expand
routine measurement of quality metrics and to identify the interventions that are
most effective in improving quality of care.
PMID- 28410367
TI - Nitric oxide charged catheters as a potential strategy for prevention of hospital
acquired infections.
AB - BACKGROUND: Catheter-Associated Hospital-Acquired Infections (HAI's) are caused
by biofilm-forming bacteria. Using a novel approach, we generated anti-infective
barrier on catheters by charging them with Nitric Oxide (NO), a naturally
produced gas molecule. NO is slowly released from the catheter upon contact with
physiological fluids, and prevents bacterial colonization and biofilm formation
onto catheter surfaces. AIMS AND METHODS: The aim of the study was to assess the
anti-infective properties of NO-charged catheters exposed to low concentration
(up to 103 CFU/ml) of microbial cells in-vitro. We assessed NO-charged tracheal
tubes using Pseudomonas aeruginosa, dialysis and biliary catheters using
Escherichia coli, and urinary catheters using E. coli, Candida albicans or
Enterococcus faecalis. Safety and tolerability of NO-charged urinary catheters
were evaluated in a phase 1 clinical study in 12 patients. Six patients were
catheterized with NO-charged catheters (NO-group), followed by 6 patients
catheterized with regular control catheters (CT-group). Comparison of safety
parameters between the study groups was performed. RESULTS: NO-charged tracheal,
dialysis biliary and urinary catheters prevented P. aeruginosa, E. coli and C.
albicans attachment and colonization onto their surfaces and eradicated
corresponding planktonic microbial cells in the surrounding media after 24-48
hours, while E. faecalis colonization onto urinary catheters was reduced by 1 log
compared to controls. All patients catheterized with an NO-charged urinary
catheter successfully completed the study without experiencing NO-related AE's or
serious AE's (SAE's). CONCLUSION: These data highlight the potential of NO-based
technology as potential platform for preventing catheter-associated HAI's.
PMID- 28410368
TI - Comprehensive bioinformatics analysis of Mycoplasma pneumoniae genomes to
investigate underlying population structure and type-specific determinants.
AB - Mycoplasma pneumoniae is a significant cause of respiratory illness worldwide.
Despite a minimal and highly conserved genome, genetic diversity within the
species may impact disease. We performed whole genome sequencing (WGS) analysis
of 107 M. pneumoniae isolates, including 67 newly sequenced using the Pacific
BioSciences RS II and/or Illumina MiSeq sequencing platforms. Comparative genomic
analysis of 107 genomes revealed >3,000 single nucleotide polymorphisms (SNPs) in
total, including 520 type-specific SNPs. Population structure analysis supported
the existence of six distinct subgroups, three within each type. We developed a
predictive model to classify an isolate based on whole genome SNPs called against
the reference genome into the identified subtypes, obviating the need for genome
assembly. This study is the most comprehensive WGS analysis for M. pneumoniae to
date, underscoring the power of combining complementary sequencing technologies
to overcome difficult-to-sequence regions and highlighting potential differential
genomic signatures in M. pneumoniae.
PMID- 28410369
TI - Quantitative assessment of the impact of partially protective anti
schistosomiasis vaccines.
AB - BACKGROUND: Mass drug administration (MDA) of praziquantel has been the
intervention of choice against schistosomiasis but with limited success in
interrupting the transmission. The development of anti-Schistosoma vaccines is
underway. Our objective is to quantify the population-level impact of anti
Schistosoma vaccines when administered alone and in combination with mass drug
administration (MDA) and determine factors in vaccine design and public health
implementation that optimize vaccination role in schistosomiasis control and
elimination. METHODS AND FINDINGS: We developed a deterministic compartmental
model simulation of schistosomiasis transmission in a high-risk Kenyan community,
including stratification by age, parasite burden, and vaccination status. The
modeled schistosomiasis vaccines differed in terms of vaccine duration of
protection (durability) and three biological efficacies. These are vaccine
susceptibility effect (SE) of reducing person's susceptibility to Schistosoma
acquisition, vaccine mortality effect (ME) of reducing established worm burden
and vaccine fecundity effect (FE) of reducing egg release by mature worms. We
quantified the population-level impact of vaccination over two decades under
diverse vaccination schemes (childhood vs. mass campaigns), with different age
targeting scenarios, different risk settings, and with combined intervention with
MDA. We also assessed the sensitivity of our predictions to uncertainties in
model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME
efficacies, 10 years' durability, provided by mass vaccination every 10 years,
reduced host prevalence, mean intensity, incidence, and patent snail prevalence
to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from
endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was
found when coverage did not encompass all potential contaminators, and childhood
only vaccination schemes showed delayed and lower impact. In lower prevalence
settings, the base case vaccine generated a proportionately smaller impact. A
substantially larger vaccine program effect was generated when MDA + mass
vaccination was provided every 5 years, which could be achieved by an MDA-only
program only if drug was offered annually. Vaccine impact on schistosomiasis
transmission was sensitive to a number of parameters including vaccine
efficacies, human contact rates with water, human density, patent snails' rate of
patency and lifespan, and force of infection to snails. CONCLUSIONS: To be
successful a vaccine-based control strategy will need a moderately to highly
effective formulation combined with early vaccination of potential contaminators
and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA
only program, vaccination combined with MDA accelerates and prolongs the impact
by reducing the acquisition of new worms and reducing egg release from residual
worms.
PMID- 28410370
TI - A systematic screen for morphological abnormalities during fission yeast sexual
reproduction identifies a mechanism of actin aster formation for cell fusion.
AB - In non-motile fungi, sexual reproduction relies on strong morphogenetic changes
in response to pheromone signaling. We report here on a systematic screen for
morphological abnormalities of the mating process in fission yeast
Schizosaccharomyces pombe. We derived a homothallic (self-fertile) collection of
viable deletions, which, upon visual screening, revealed a plethora of phenotypes
affecting all stages of the mating process, including cell polarization, cell
fusion and sporulation. Cell fusion relies on the formation of the fusion focus,
an aster-like F-actin structure that is marked by strong local accumulation of
the myosin V Myo52, which concentrates secretion at the fusion site. A secondary
screen for fusion-defective mutants identified the myosin V Myo51-associated
coiled-coil proteins Rng8 and Rng9 as critical for the coalescence of the fusion
focus. Indeed, rng8Delta and rng9Delta mutant cells exhibit multiple stable dots
at the cell-cell contact site, instead of the single focus observed in wildtype.
Rng8 and Rng9 accumulate on the fusion focus, dependent on Myo51 and tropomyosin
Cdc8. A tropomyosin mutant allele, which compromises Rng8/9 localization but not
actin binding, similarly leads to multiple stable dots instead of a single focus.
By contrast, myo51 deletion does not strongly affect fusion focus coalescence. We
propose that focusing of the actin filaments in the fusion aster primarily relies
on Rng8/9-dependent cross-linking of tropomyosin-actin filaments.
PMID- 28410372
TI - Correction: Gifsy-1 Prophage IsrK with Dual Function as Small and Messenger RNA
Modulates Vital Bacterial Machineries.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1005975.].
PMID- 28410371
TI - Determining the role of missense mutations in the POU domain of HNF1A that reduce
the DNA-binding affinity: A computational approach.
AB - Maturity-onset diabetes of the young type 3 (MODY3) is a non-ketotic form of
diabetes associated with poor insulin secretion. Over the past years, several
studies have reported the association of missense mutations in the Hepatocyte
Nuclear Factor 1 Alpha (HNF1A) with MODY3. Missense mutations in the POU
homeodomain (POUH) of HNF1A hinder binding to the DNA, thereby leading to a
dysfunctional protein. Missense mutations of the HNF1A were retrieved from public
databases and subjected to a three-step computational mutational analysis to
identify the underlying mechanism. First, the pathogenicity and stability of the
mutations were analyzed to determine whether they alter protein structure and
function. Second, the sequence conservation and DNA-binding sites of the mutant
positions were assessed; as HNF1A protein is a transcription factor. Finally, the
biochemical properties of the biological system were validated using molecular
dynamic simulations in Gromacs 4.6.3 package. Two arginine residues (131 and 203)
in the HNF1A protein are highly conserved residues and contribute to the function
of the protein. Furthermore, the R131W, R131Q, and R203C mutations were predicted
to be highly deleterious by in silico tools and showed lower binding affinity
with DNA when compared to the native protein using the molecular docking
analysis. Triplicate runs of molecular dynamic (MD) simulations (50ns) revealed
smaller changes in patterns of deviation, fluctuation, and compactness, in
complexes containing the R131Q and R131W mutations, compared to complexes
containing the R203C mutant complex. We observed reduction in the number of
intermolecular hydrogen bonds, compactness, and electrostatic potential, as well
as the loss of salt bridges, in the R203C mutant complex. Substitution of
arginine with cysteine at position 203 decreases the affinity of the protein for
DNA, thereby destabilizing the protein. Based on our current findings, the MD
approach is an important tool for elucidating the impact and affinity of
mutations in DNA-protein interactions and understanding their function.
PMID- 28410373
TI - Parallel reorganization of protein function in the spindle checkpoint pathway
through evolutionary paths in the fitness landscape that appear neutral in
laboratory experiments.
AB - Regulatory networks often increase in complexity during evolution through gene
duplication and divergence of component proteins. Two models that explain this
increase in complexity are: 1) adaptive changes after gene duplication, such as
resolution of adaptive conflicts, and 2) non-adaptive processes such as
duplication, degeneration and complementation. Both of these models predict
complementary changes in the retained duplicates, but they can be distinguished
by direct fitness measurements in organisms with short generation times.
Previously, it has been observed that repeated duplication of an essential
protein in the spindle checkpoint pathway has occurred multiple times over the
eukaryotic tree of life, leading to convergent protein domain organization in its
duplicates. Here, we replace the paralog pair in S. cerevisiae with a single-copy
protein from a species that did not undergo gene duplication. Surprisingly, using
quantitative fitness measurements in laboratory conditions stressful for the
spindle-checkpoint pathway, we find no evidence that reorganization of protein
function after gene duplication is beneficial. We then reconstruct several
evolutionary intermediates from the inferred ancestral network to the extant one,
and find that, at the resolution of our assay, there exist stepwise mutational
paths from the single protein to the divergent pair of extant proteins with no
apparent fitness defects. Parallel evolution has been taken as strong evidence
for natural selection, but our results suggest that even in these cases,
reorganization of protein function after gene duplication may be explained by
neutral processes.
PMID- 28410375
TI - Coping strategies related to food insecurity at the household level in
Bangladesh.
AB - INTRODUCTION: In connection to food insecurity, adaptation of new techniques or
alteration of regular behavior is executed that translates to coping strategies.
This paper has used data from food security and nutrition surveillance project
(FSNSP), which collects information from a nationally representative sample in
Bangladesh on coping behaviors associated with household food insecurity. To
complement the current understanding of different coping strategies implemented
by the Bangladeshi households, the objective of this paper has been set to
examine the demographic and socio-economic characteristics of the food insecure
households which define their propensity towards adaptation of different types of
coping strategies. METHODOLOGY: FSNSP follows a repeated cross-sectional survey
design. Information of 23,374 food insecure households available from February
2011 to November 2013 was selected for the analyses. Coping strategies were
categorized as financial, food compromised and both. Multinomial logistic
regression was employed to draw inference. RESULTS: Majority of the households
were significantly more inclined to adopt both multiple financial and food
compromisation coping strategies. Post-aman season, educational status of the
household head and household women, occupation of the household's main earner,
household income, food insecurity status, asset, size and possession of
agricultural land were found to be independently and significantly associated
with adaptation of both financial and food compromisation coping strategies
relative to only financial coping strategies. The relative risk ratio of adopting
food compromisation coping relative to financial coping strategies when compared
to mildly food insecure households, was 4.54 times higher for households with
moderate food insecurity but 0.3 times lower when the households were severely
food insecure. Whereas, households were 8.04 times and 4.98 times more likely to
adopt both food compromisation and financial relative to only financial coping
strategies if moderately and severely food insecure respectively when compared to
being mildly food insecure. CONCLUSION: Households suffering from moderate and
severe food insecurity, are more likely to adopt both financial and food
compromisation coping strategies.
PMID- 28410374
TI - Factors influencing postnatal Option B+ participation and breastfeeding duration
among HIV-positive women in Lilongwe District, Malawi: A qualitative study.
AB - To ensure the health of mothers and children, prevention of mother-to-child HIV
transmission (PMTCT) programs test women for HIV, engage HIV-positive women in
care, and promote recommended breastfeeding practices. Under Malawi's Option B+
PMTCT program, ~20% of women are lost-to-follow-up (LTFU) and little is known
about their breastfeeding practices. The purpose of this study is to describe
facilitators and barriers to Option B+ participation and how participation
influences breastfeeding duration. We conducted in-depth interviews with HIV
positive women in Option B+ (n = 32) or LTFU from Option B+ (n = 32). They were
recruited from four government clinics in Lilongwe District and had a child aged
0-23 months. Women in Option B+ had better disclosure experiences and more social
support than LTFU women. The most common reasons for LTFU were fear of HIV
disclosure, anticipated or experienced stigma, and insufficient social support.
Other reasons included: non-acceptance of HIV status, antiretroviral therapy
(ART) side effects, lack of funds for transport, and negative experiences with
clinic staff. Worries about possible transmission, even while on ART, influenced
timing of weaning for some women in Option B+. Despite their knowledge of the
risk of HIV transmission to the child, most LTFU women continued to breastfeed
after stopping ART because they considered breastmilk to be an important source
of nutrients for the child. Given that HIV-positive Malawian women LTFU from
Option B+ breastfeed in the absence of ART, efforts are needed to use evidence
based strategies to address the barriers to Option B+ participation and avert
preventable transmission through breastmilk.
PMID- 28410376
TI - Tuber indicum shapes the microbial communities of ectomycorhizosphere soil and
ectomycorrhizae of an indigenous tree (Pinus armandii).
AB - The aim of this study was to investigate the effect of an ectomycorrhizal fungus
(Tuber indicum) on the diversity of microbial communities associated with an
indigenous tree, Pinus armandii, and the microbial communities in the surrounding
ectomycorhizosphere soil. High-throughput sequencing was used to analyze the
richness of microbial communities in the roots or rhizosphere of treatments with
or without ectomycorrhizae. The results indicated that the bacterial diversity of
ectomycorhizosphere soil was significantly lower compared with the control soil.
Presumably, the dominance of truffle mycelia in ectomycorhizosphere soil (80.91%)
and ectomycorrhizae (97.64%) was the main factor that resulted in lower diversity
and abundance of endophytic pathogenic fungi, including Fusarium, Monographella,
Ustilago and Rhizopus and other competitive mycorrhizal fungi, such as Amanita,
Lactarius and Boletus. Bacterial genera Reyranena, Rhizomicrobium, Nordella,
Pseudomonas and fungal genera, Cuphophyllus, Leucangium, Histoplasma were
significantly more abundant in ectomycorrhizosphere soil and ectomycorrhizae.
Hierarchical cluster analysis of the similarities between rhizosphere and
ectomycorrhizosphere soil based on the soil properties differed significantly,
indicating the mycorrhizal synthesis may have a feedback effect on soil
properties. Meanwhile, some soil properties were significantly correlated with
bacterial and fungal diversity in the rhizosphere or root tips. Overall, this
work illustrates the interactive network that exists among ectomycorrhizal fungi,
soil properties and microbial communities associated with the host plant and
furthers our understanding of the ecology and cultivation of T. indicum.
PMID- 28410377
TI - Plasma from patients with anti-glomerular basement membrane disease could
recognize microbial peptides.
AB - Infection has long been suspected as a trigger of autoimmune diseases, and
molecular mimicry mechanism was hypothesized in this study. Microbe originated
peptides were searched from the Uniprot database based on a previous defined
critical amino acid motif within alpha3129-150, isoleucine137, tryptophan140,
glycine142, phenylalanine 143 and phenylalanine 145. 23826 microbial peptides
were identified using our searching strategy, among which seven were related with
human infections. Circulating IgG and IgM antibodies against the seven microbial
peptides were detected using ELISA in 76 patients with anti-GBM disease. Four
peptides were recognized by both IgG and IgM antibodies, and one peptide was
recognized by IgG antibodies only. Peptides from Bacteroides, Saccharomyces
cerevisiae, and Bifidobacterium thermophilum possessed the highest recognition
frequency with the prevalence of 73.7%, 61.8% and 67.1% for IgG, 56.6%, 44.7% and
67.1% for IgM in anti-GBM patients. Patients with antibodies against these
microbial peptides showed more severe kidney injury, including higher serum
creatinine and higher percentage of crescent formation. In conclusion, antibodies
against microbial peptides were identified in the circulation of anti-GBM
patients, implying its etiological role in eliciting autoimmune response against
alpha3(IV)NC1 through molecular mimicry.
PMID- 28410378
TI - Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse
model of Alzheimer's disease: Alleviation by pantethine.
AB - Astrocytes play critical roles in central nervous system homeostasis and support
of neuronal function. A better knowledge of their response may both help
understand the pathophysiology of Alzheimer's disease (AD) and implement new
therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg
thereafter) to generate astrocyte cultures and investigate the impact of the
genotype on metabolic changes and astrocytes activation. Metabolomic analysis
showed that Tg astrocytes exhibited changes in the glycolytic pathway and
tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells. Tg astrocytes
displayed also a prominent basal inflammatory status, with accentuated reactivity
and increased expression of the inflammatory cytokine interleukin-1 beta (IL
1beta). Compensatory mechanisms were activated in Tg astrocytes, including: i)
the hexose monophosphate shunt with the consequent production of reducing
species; ii) the induction of hypoxia inducible factor-1 alpha (HIF-1alpha),
known to protect against amyloid-beta (Abeta) toxicity. Such events were
associated with the expression by Tg astrocytes of human isoforms of both amyloid
precursor protein (APP) and presenilin-1 (PS1). Similar metabolic and
inflammatory changes were induced in WT astrocytes by exogenous Abeta peptide.
Pantethine, the vitamin B5 precursor, known to be neuroprotective and anti
inflammatory, alleviated the pathological pattern in Tg astrocytes as well as WT
astrocytes treated with Abeta. In conclusion, our data enlighten the dual
pathogenic/protective role of astrocytes in AD pathology and the potential
protective role of pantethine.
PMID- 28410379
TI - New insights into valve-related intramural and intracellular bacterial diversity
in infective endocarditis.
AB - AIMS: In infective endocarditis (IE), a severe inflammatory disease of the
endocardium with an unchanged incidence and mortality rate over the past decades,
only 1% of the cases have been described as polymicrobial infections based on
microbiological approaches. The aim of this study was to identify potential
biodiversity of bacterial species from infected native and prosthetic valves.
Furthermore, we compared the ultrastructural micro-environments to detect the
localization and distribution patterns of pathogens in IE. MATERIAL AND METHODS:
Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the
entire bacterial community within a single sample, we investigated the
biodiversity of infectious bacterial species from resected native and prosthetic
valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the
ultrastructural infected valve micro-environment by focused ion beam scanning
electron microscopy (FIB-SEM). RESULTS: Biodiversity was detected in 7 of 8
resected heart valves. This comprised 13 bacterial genera and 16 species. In
addition to 11 pathogens already described as being IE related, 5 bacterial
species were identified as having a novel association. In contrast, valve and
blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and
did not show any relevant antibiotic resistance. The antibiotics chosen on this
basis for treatment, however, did not cover the bacterial spectra identified by
our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural
distribution patterns of infective bacteria, intracellular localization with
evidence of bacterial immune escape mechanisms was identified. CONCLUSION: The
high frequency of polymicrobial infections, pathogen diversity, and intracellular
persistence of common IE-causing bacteria may provide clues to help explain the
persistent and devastating mortality rate observed for IE. Improved bacterial
diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy
may result in improved outcomes.
PMID- 28410380
TI - Interleukin-10 and prostaglandin E2 have complementary but distinct suppressive
effects on Toll-like receptor-mediated dendritic cell activation in ovarian
carcinoma.
AB - Dendritic cells (DC) have the potential to instigate a tumour-specific immune
response, but their ability to prime naive lymphocytes depends on their
activation status. Thus, for tumour immunotherapy to be effective, the provision
of appropriate DC activation stimuli such as Toll-like receptor (TLR) agonists is
crucial in order to overcome immunosuppression associated with the tumour
microenvironment. To address this, we investigated how ovarian carcinoma (OC)
associated ascites impedes activation of DC by TLR agonists. Our results show
that ascites reduces the TLR-mediated up-regulation of CD86 and partially
inhibits the production of the pro-inflammatory cytokines interleukin 6 (IL-6),
IL-12 and tumour necrosis factor alpha (TNFalpha) in monocyte-derived DC from
healthy controls. We further observe an impaired T cell stimulatory capacity of
DC upon activation with TLR agonists in the presence of ascites, indicating that
their functionality is affected by the immunosuppressive factors. We identify IL
10 and prostaglandin E2 (PGE2) as the pivotal immunosuppressive components in OC
associated ascites compromising TLR-mediated DC activation. Interestingly, IL-10
is present in both ascites from patients with malignant OC and in peritoneal
fluid from patients with benign ovarian conditions and both fluids have similar
ability to reduce TLR-mediated DC activation. However, depletion of IL-10 from
ascites revealed that the presence of paracrine IL-10 is not crucial for ascites
mediated suppression of DC activation in response to TLR activation. Unlike IL
10, PGE2 is absent from peritoneal fluid of patients with benign conditions and
selectively reduces TNFalpha induction in response to TLR-mediated activation in
the presence of OC-associated ascites. Our study highlights PGE2 as an
immunosuppressive component of the malignant OC microenvironment rendering PGE2 a
potentially important target for immunotherapy in OC.
PMID- 28410381
TI - Qualitative analysis of the impact of Oral Potentially Malignant Disorders on
daily life activities.
AB - OBJECTIVE: To evaluate the impact of Oral Potentially Malignant Disorders (OPMD)
on daily life activities. MATERIALS AND METHODS: Patients diagnosed with Oral
Leukoplakia, Oral submucous fibrosis and Oral Lichen Planus attending the Oral
Medicine clinic of Panineeya Institute of Dental Sciences & Research Centre,
Hyderabad, India were invited to participate. Eighteen interviews and three focus
groups were conducted in a non-clinical setting. Voice recordings were
transcribed and translated from Telugu to English. Data coding was performed
using the NVivo software. RESULTS: Sample size for this qualitative study
comprised 32 patients. Four main themes emerged: (1) difficulties with diagnosis
and knowledge about the condition, (2) physical impairment and functional
limitations, (3) psychological and social wellbeing and (4) effects of treatment
on daily life. In a majority of the patients, most of the interview time was
spent discussing physical impairment and functional limitations. Patients also
reported their mouth condition having a debilitating effect on their
psychological well-being and social interactions. CONCLUSIONS: 'Physical
impairment and functional limitations' was the most important theme for many of
the patients. However, the impacts of OPMD also extended beyond physical
impairment and functional limitations to aspects of daily living, notably
psychological and social wellbeing.
PMID- 28410382
TI - Controlling cholera in the Ouest Department of Haiti using oral vaccines.
AB - Following the 2010 cholera outbreak in Haiti, a plan was initiated to provide
massive improvements to the sanitation and drinking water infrastructure in order
to eliminate cholera from the island of Hispaniola by 2023. Six years and a half
billion dollars later, there is little evidence that any substantial improvements
have been implemented; with increasing evidence that cholera has become endemic.
Thus, it is time to explore strategies to control cholera in Haiti using oral
cholera vaccines (OCVs). The potential effects of mass administration of OCVs on
cholera transmission were assessed using dynamic compartment models fit to
cholera incidence data from the Ouest Department of Haiti. The results indicated
that interventions using an OCV that was 60% effective could have eliminated
cholera transmission by August 2012 if started five weeks after the initial
outbreak. A range of analyses on the ability of OCV interventions started January
1, 2017 to eliminate cholera transmission by 2023 were performed by considering
different combinations of vaccine efficacies, vaccine administration rates, and
durations of protective immunity. With an average of 50 weeks for the waiting
time to vaccination and an average duration of three years for the vaccine
induced immunity, all campaigns that used an OCV with a vaccine efficacy of at
least 60% successfully eliminated cholera transmission by 2023. The results of
this study suggest that even with a relatively wide range of vaccine efficacies,
administration rates, and durations of protective immunity, future epidemics
could be controlled at a relatively low cost using mass administration of OCVs in
Haiti.
PMID- 28410383
TI - Shared processing in multiple object tracking and visual working memory in the
absence of response order and task order confounds.
AB - To understand how the visual system represents multiple moving objects and how
those representations contribute to tracking, it is essential that we understand
how the processes of attention and working memory interact. In the work described
here we present an investigation of that interaction via a series of tracking and
working memory dual-task experiments. Previously, it has been argued that
tracking is resistant to disruption by a concurrent working memory task and that
any apparent disruption is in fact due to observers making a response to the
working memory task, rather than due to competition for shared resources.
Contrary to this, in our experiments we find that when task order and response
order confounds are avoided, all participants show a similar decrease in both
tracking and working memory performance. However, if task and response order
confounds are not adequately controlled for we find substantial individual
differences, which could explain the previous conflicting reports on this topic.
Our results provide clear evidence that tracking and working memory tasks share
processing resources.
PMID- 28410384
TI - Relay discovery and selection for large-scale P2P streaming.
AB - In peer-to-peer networks, application relays have been commonly used to provide
various networking services. The service performance often improves significantly
if a relay is selected appropriately based on its network location. In this
paper, we studied the location-aware relay discovery and selection problem for
large-scale P2P streaming networks. In these large-scale and dynamic overlays, it
incurs significant communication and computation cost to discover a sufficiently
large relay candidate set and further to select one relay with good performance.
The network location can be measured directly or indirectly with the tradeoffs
between timeliness, overhead and accuracy. Based on a measurement study and the
associated error analysis, we demonstrate that indirect measurements, such as
King and Internet Coordinate Systems (ICS), can only achieve a coarse estimation
of peers' network location and those methods based on pure indirect measurements
cannot lead to a good relay selection. We also demonstrate that there exists
significant error amplification of the commonly used "best-out-of-K" selection
methodology using three RTT data sets publicly available. We propose a two-phase
approach to achieve efficient relay discovery and accurate relay selection.
Indirect measurements are used to narrow down a small number of high-quality
relay candidates and the final relay selection is refined based on direct
probing. This two-phase approach enjoys an efficient implementation using the
Distributed-Hash-Table (DHT). When the DHT is constructed, the node keys carry
the location information and they are generated scalably using indirect
measurements, such as the ICS coordinates. The relay discovery is achieved
efficiently utilizing the DHT-based search. We evaluated various aspects of this
DHT-based approach, including the DHT indexing procedure, key generation under
peer churn and message costs.
PMID- 28410385
TI - Structural power and the evolution of collective fairness in social networks.
AB - From work contracts and group buying platforms to political coalitions and
international climate and economical summits, often individuals assemble in
groups that must collectively reach decisions that may favor each part unequally.
Here we quantify to which extent our network ties promote the evolution of
collective fairness in group interactions, modeled by means of Multiplayer
Ultimatum Games (MUG). We show that a single topological feature of social
networks-which we call structural power-has a profound impact on the tendency of
individuals to take decisions that favor each part equally. Increased fair
outcomes are attained whenever structural power is high, such that the networks
that tie individuals allow them to meet the same partners in different groups,
thus providing the opportunity to strongly influence each other. On the other
hand, the absence of such close peer-influence relationships dismisses any
positive effect created by the network. Interestingly, we show that increasing
the structural power of a network leads to the appearance of well-defined modules
as found in human social networks that often exhibit community structure
providing an interaction environment that maximizes collective fairness.
PMID- 28410386
TI - Radiation dose reduction in pediatric great vessel stent computed tomography
using iterative reconstruction: A phantom study.
AB - BACKGROUND: To study dose reduction using iterative reconstruction (IR) for
pediatric great vessel stent computed tomography (CT). METHODS: Five different
great vessel stents were separately placed in a gel-containing plastic holder
within an anthropomorphic chest phantom. The stent lumen was filled with diluted
contrast gel. CT acquisitions were performed at routine dose, 52% and 81% reduced
dose and reconstructed with filtered back projection (FBP) and IR. Objective
image quality in terms of noise, signal-to-noise ratio (SNR) and contrast-to
noise ratio (CNR) as well as subjective image quality were evaluated. RESULTS:
Noise, SNR and CNR were improved with IR at routine and 52% reduced dose,
compared to FBP at routine dose. The lowest dose level resulted in decreased
objective image quality with both FBP and IR. Subjective image quality was
excellent at all dose levels. CONCLUSION: IR resulted in improved objective image
quality at routine dose and 52% reduced dose, while objective image quality
deteriorated at 81% reduced dose. Subjective image quality was not affected by
dose reduction.
PMID- 28410387
TI - Mathematical algorithm for the automatic recognition of intestinal parasites.
AB - Parasitic infections are generally diagnosed by professionals trained to
recognize the morphological characteristics of the eggs in microscopic images of
fecal smears. However, this laboratory diagnosis requires medical specialists
which are lacking in many of the areas where these infections are most prevalent.
In response to this public health issue, we developed a software based on pattern
recognition analysis from microscopi digital images of fecal smears, capable of
automatically recognizing and diagnosing common human intestinal parasites. To
this end, we selected 229, 124, 217, and 229 objects from microscopic images of
fecal smears positive for Taenia sp., Trichuris trichiura, Diphyllobothrium
latum, and Fasciola hepatica, respectively. Representative photographs were
selected by a parasitologist. We then implemented our algorithm in the open
source program SCILAB. The algorithm processes the image by first converting to
gray-scale, then applies a fourteen step filtering process, and produces a
skeletonized and tri-colored image. The features extracted fall into two general
categories: geometric characteristics and brightness descriptions. Individual
characteristics were quantified and evaluated with a logistic regression to model
their ability to correctly identify each parasite separately. Subsequently, all
algorithms were evaluated for false positive cross reactivity with the other
parasites studied, excepting Taenia sp. which shares very few morphological
characteristics with the others. The principal result showed that our algorithm
reached sensitivities between 99.10%-100% and specificities between 98.13%-
98.38% to detect each parasite separately. We did not find any cross-positivity
in the algorithms for the three parasites evaluated. In conclusion, the results
demonstrated the capacity of our computer algorithm to automatically recognize
and diagnose Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and
Fasciola hepatica with a high sensitivity and specificity.
PMID- 28410388
TI - Tiger on the prowl: Invasion history and spatio-temporal genetic structure of the
Asian tiger mosquito Aedes albopictus (Skuse 1894) in the Indo-Pacific.
AB - BACKGROUND: Within the last century, increases in human movement and
globalization of trade have facilitated the establishment of several highly
invasive mosquito species in new geographic locations with concurrent major
environmental, economic and health consequences. The Asian tiger mosquito, Aedes
albopictus, is an extremely invasive and aggressive daytime-biting mosquito that
is a major public health threat throughout its expanding range.
METHODOLOGY/PRINCIPAL FINDINGS: We used 13 nuclear microsatellite loci (on 911
individuals) and mitochondrial COI sequences to gain a better understanding of
the historical and contemporary movements of Ae. albopictus in the Indo-Pacific
region and to characterize its population structure. Approximate Bayesian
computation (ABC) was employed to test competing historical routes of invasion of
Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC
results show that Ae. albopictus was most likely introduced to New Guinea via
mainland Southeast Asia, before colonizing the Solomon Islands via either Papua
New Guinea or SE Asia. The analysis also supported that the recent incursion into
northern Australia's Torres Strait Islands was seeded chiefly from Indonesia. For
the first time documented in this invasive species, we provide evidence of a
recently colonized population (the Torres Strait Islands) that has undergone
rapid temporal changes in its genetic makeup, which could be the result of
genetic drift or represent a secondary invasion from an unknown source.
CONCLUSIONS/SIGNIFICANCE: There appears to be high spatial genetic structure and
high gene flow between some geographically distant populations. The species'
genetic structure in the region tends to favour a dispersal pattern driven mostly
by human movements. Importantly, this study provides a more widespread sampling
distribution of the species' native range, revealing more spatial population
structure than previously shown. Additionally, we present the most probable
invasion history of this species in the Australasian region using ABC analysis.
PMID- 28410389
TI - Molecular subtyping of Treponema pallidum and associated factors of serofast
status in early syphilis patients: Identified novel genotype and cytokine marker.
AB - Serofast, a persistent nontreponemal serological response observed in early
syphilis patients after conventional treatment, remains a concern of clinicians
and syphilis patients. No consensus has been established, however, that defines
an effective treatment strategy and clarifies the pathogenesis. In this study,
517 patients with early syphilis were enrolled and treated. Twelve months after
treatment, 79.3% (410/517) of patients achieved serological cure, 20.1% (104/517)
were serofast, and 0.6% (3/517) were serological failures. Multivariate analysis
demonstrated that older age (>40 years) and lower baseline RPR titer (<= 1:8)
were associated with serofast status. We also identified 21 T. pallidum molecular
subtypes among early syphilis patients and detected a new subtype, 14i/a. We
found that the proportion of 14i/a type in serofast patients was significantly
higher than that in patients with serological cure, predicting an increasing risk
of serofast status. Levels of chemerin were higher in the serum of serofast cases
than serological cure cases, potentially indicating a novel cytokine marker for
serofast in early syphilis patients after therapy. We hope that these results
contribute to improve guidelines for the management of syphilis patients who
experience serofast.
PMID- 28410391
TI - Cilia and sensory signaling: The journey from "animalcules" to human disease.
AB - Nearly all cell types in mammals contain cilia, small rod-like or more elaborate
structures that extend from the cell surface. Cilia house signaling proteins that
allow the cell to sample their environment and respond appropriately. Mutations
in ciliary genes alter the functions of a broad range of cell and tissue types,
including sensory and central neurons, and underlie a collection of heterogeneous
human disorders called ciliopathies. Here, I highlight the critical contributions
of nearly three centuries of research in diverse organisms to our current
knowledge of cilia function in sensory signaling and human disease.
PMID- 28410390
TI - Accessory gene regulator (Agr) functionality in Staphylococcus aureus derived
from lower respiratory tract infections.
AB - OBJECTIVE: Characterization of Staphylococcus aureus clinical isolates derived
from lower respiratory tract infections (LRTIs), and correlation between the
functionality of the accessory gene regulator (Agr) and genotypic and phenotypic
characteristics, clinical variables and clinical outcome. METHODS: S aureus
isolates derived from LRTIs and control groups (nasal carriage and bacteraemia)
were genotyped using StaphyType DNA microarray. Agr activity was evaluated using
the CAMP synergistic haemolysis assay and the Vesicle Lysis Test (VLT).
Discordant strains were analysed by quantitative reverse-transcriptase real-time
PCR (qRT-PCR). RESULTS: Agr was functional in 79.7% and 84.5% of strains
according to the CAMP and VLT assays respectively. Higher concordance with RNAIII
expression measured by qRT-PCR was observed with the VLT assay (76.2%) compared
with the CAMP assay (23.8%). No statistically significant differences were
observed in Agr functionality between the study groups, nor the
phenotypical/genotypical bacterial characteristics. No association between
increased mortality/respiratory complications and Agr function was observed.
CONCLUSIONS: Agr activity was high (82.2%) in isolates from LRTIs suggesting the
importance of this global regulator in lower respiratory tract colonisation and
infection. However, equally high Agr activity was observed in isolates derived
from nasal carriage and bacteraemia, contradictory to previous observations. Agr
functionality measured by the VLT assay was superior to CAMP assay.
PMID- 28410392
TI - CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous
cell carcinoma.
AB - Squamous cell carcinoma of the skin (SCC) represents one of the most common
cancers in the general population and is associated with a substantial risk of
metastasis. Previous work uncovered the functional role of CYFIP1 in epithelial
tumors as an invasion inhibitor. It was down-regulated in some cancers and
correlated with the metastatic properties of these malignant cells. We
investigated its role and expression mechanisms in SCC. We analyzed the
expression of CYFIP1 in patient derived SCC, primary keratinocytes and SCC cell
lines, and correlated it to the differentiation and NOTCH1 levels. We analyzed
the effects of Notch1 manipulation on CYFIP1 expression and confirmed the biding
of Notch1 to the CYFIP1 promoter. CYFIP1 expression was down-regulated in SCC and
correlated inversely with histological differentiation of tumors. As keratinocyte
differentiation depends on Notch1 signaling, we investigated the influence of
Notch1 on CYFIP1 expression. CYFIP1 mRNA was highly increased in human Notch1
overexpressing keratinocytes. Further manipulation of the Notch1 pathway in
keratinocytes impacted CYFIP1 levels and chromatin immunoprecipitation assay
confirmed the direct binding of Notch1 to the CYFIP1 promoter. CYFIP1 may be a
link between loss of differentiation and invasive potential in malignant
keratinocytes of cutaneous squamous cell carcinoma.
PMID- 28410393
TI - Counting distance: Effects of egocentric distance on numerical perception.
AB - Numerical value is long known to be associated with a variety of magnitude
representations, such as size, time and space. The present study focused on the
interactive relations of numerical magnitude with a spatial factor which is
dominant in everyday vision and is often overlooked, namely, egocentric distance,
or depth. We hypothesized that digits denoting large magnitudes are associated
with large perceived distances, and vice versa. While the relations of numerical
value and size have been long documented, effects of egocentric distance on
numeral perception have been scarcely investigated, presumably due to the
difficulty to disentangle size and depth factors within three-dimensional visual
displays. The current study aimed to assess the potential linkage between
egocentric distance and number magnitude, while neutralizing any perceived and/or
physical size parameters of target digits. In Experiment 1, participants
conducted a numeral size-classification task ('bigger or smaller than 5'), to
which they responded with a near-to-body or a far-from-body key. Results revealed
shorter responses for small than for large numbers when responded with a key
positioned close to the body, and for large than small numbers when responded
with a key positioned far from the body (regardless of hand-key mapping).
Experiment 2 used verbal stimuli denoting near/remote concepts as irrelevant
primes to target digits, further demonstrating a priming effect of conceived
distance on numerical value processing. Collectively, our results suggest that
distance magnitudes are associatively linked to numerical magnitudes and may
affect digit processing independently of the effects of visual size.
PMID- 28410394
TI - Non-fragile mixed Hinfinity and passive synchronization of Markov jump neural
networks with mixed time-varying delays and randomly occurring controller gain
fluctuation.
AB - This paper studies the non-fragile mixed Hinfinity and passive synchronization
problem for Markov jump neural networks. The randomly occurring controller gain
fluctuation phenomenon is investigated for non-fragile strategy. Moreover, the
mixed time-varying delays composed of discrete and distributed delays are
considered. By employing stochastic stability theory, synchronization criteria
are developed for the Markov jump neural networks. On the basis of the derived
criteria, the non-fragile synchronization controller is designed. Finally, an
illustrative example is presented to demonstrate the validity of the control
approach.
PMID- 28410395
TI - The role of temporal predictability for early attentional adjustments after
conflict.
AB - A frequently-studied phenomenon in cognitive-control research is conflict
adaptation, or the finding that congruency effects are smaller after incongruent
trials. Prominent cognitive control accounts suggest that this adaptation effect
can be explained by transient conflict-induced modulations of selective
attention, reducing congruency effects on the next trial. In the present study,
we investigated these possible attentional modulations in four experiments using
the Stroop and Flanker tasks, dissociating possible enhancements of task-relevant
information from suppression of task-irrelevant information by varying when this
information was presented. In two experiments, the irrelevant stimulus
information was randomly presented shortly before, at the same time, or briefly
after the presentation of the relevant dimension. In the other two, irrelevant
information was always presented first, making this aspect fully predictable.
Despite the central role that attentional adjustments play in theoretical
accounts of conflict adaption, we only found evidence for such processes in one
of the four experiments. Specifically, we found a modulation of the attention
related posterior N1 event-related potential component that was consistent with
paying less attention to the irrelevant information after incongruent trials.
This was accompanied by increased inter-trial mid-frontal theta power and a theta
power conflict adaptation effect. We interpret these results as evidence for an
adaptive mechanism based on relative attentional inhibition. Importantly, this
mechanism only clearly seems to be implemented in a very specific context of high
temporal predictability, and only in the Flanker task.
PMID- 28410398
TI - Do people who experience incarceration age more quickly? Exploratory analyses
using retrospective cohort data on mortality from Ontario, Canada.
AB - OBJECTIVES: We aimed to explore whether mortality data are consistent with the
view that aging is accelerated for people with a history of incarceration
compared to the general population, using data on mortality rates and life
expectancy for persons in Ontario, Canada. METHODS: We obtained data from the
Ontario Ministry of Community Safety and Correctional Services on all adults
admitted to provincial correctional facilities in Ontario in 2000, and linked
these data with death records from provincial vital statistics between January 1,
2000 and December 31, 2012. We used life table methods to calculate mortality
rates and life expectancies for this cohort by sex and 5-year age group. We
similarly generated population comparison rates using publicly available data for
the general population of Ontario in 2006 as the midpoint of the follow up
period. We compared these mortality indices between the 2000 Ontario prison
cohort and the general population by age group and sex. RESULTS: The difference
in all-cause mortality rates between the 2000 Ontario prison cohort and the
general population was greatest for younger adults, with the prison cohort
experiencing rates of death that would be expected for persons at least 15 years
older at ages 20 to 44 for men and ages 20 to 59 for women. Life expectancy in
the 2000 Ontario prison cohort was most similar to life expectancy of persons
five years older in the general population at age intervals 20 to 45 in men and
20 to 30 in women. CONCLUSIONS: For most of adulthood, life expectancy and
mortality rates are worse for adults with a history of incarceration than for the
general population in Ontario, Canada. However, the association between mortality
and incarceration status is modified by age, with the greatest relative burden of
mortality experienced by younger persons with a history of incarceration and
modified by sex, with worse relative mortality in women. Future research should
explore the association between incarceration status and markers of aging
including mortality, morbidity and physical appearance.
PMID- 28410396
TI - Evolution of the neuraminidase gene of seasonal influenza A and B viruses in
Thailand between 2010 and 2015.
AB - The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used
for the treatment and control of influenza A and B virus infection. However, the
emergence of new influenza virus strains with reduced susceptibility to NAIs may
appear with the use of these antivirals or even naturally. We therefore screened
the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1),
A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for
the presence of substitutions previously reported to reduce susceptibility to
NAIs. We initially examined oseltamivir resistance (characterized by the H275Y
mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and
found that 0.82% (4/485) had this substitution. To further evaluate the evolution
of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69
influenza B virus strains for NA gene amplification and sequencing, which
revealed various amino acid mutations in the active site of the NA protein
previously shown to be associated with reduced susceptibility to NAIs.
Phylogenetic analysis of the influenza virus strains from this study and
elsewhere around the world, together with the estimations of nucleotide
substitution rates and selection pressure, and the predictions of B-cell epitopes
and N-linked glycosylation sites all provided evidence for the ongoing evolution
of NA. The overall rates of NA evolution for influenza A viruses were higher than
for influenza B virus at the nucleotide level, although influenza B virus
possessed more genealogical diversity than that of influenza A viruses. The
continual surveillance of the antigenic changes associated with the NA protein
will not only contribute to the influenza virus database but may also provide a
better understanding of selection pressure exerted by antiviral use.
PMID- 28410397
TI - A bis-sulphamoylated estradiol derivative induces ROS-dependent cell cycle
abnormalities and subsequent apoptosis.
AB - Clinical trials have revealed that the potential anticancer agent, 2
methoxyestradiol (2ME2) has limitations due to its low bioavailability.
Subsequently, 2ME2 derivatives including (8R,13S,14S,17S)-2-ethyl-13-methyl
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrane-3,17-diyl
bis(sulphamate) (EMBS) have shown improved efficacies in inducing apoptosis.
However, no conclusive data exist to explain the mode of action exerted by these
drugs. This study investigated the mode of action used by EMBS as a
representative of the sulphamoylated 2ME2 derivatives. Hydrogen peroxide and
superoxide production was quantified using dichlorofluorescein diacetate and
hydroethidine. Cell proliferation and mitochondrial metabolism were investigated
using crystal violet and Alamar Blue. Apoptosis was assessed using Annexin V-FITC
while mitochondrial integrity was assessed using Mitocapture. Autophagy was
visualised using LC3B II antibodies. The effects of EMBS on H2A phosphorylation
and nuclei were visualised using phospho H2A antibody and 4',6-diamidino-2
phenylindole, dihydrochloride. Data showed that EMBS exposure leads to increased
reactive oxygen species (ROS) production which is correlated with loss of cell
proliferation, mitochondrial membrane damage, decreased metabolic activity, G2/M
arrest, endoreduplication, DNA double stranded breaks, micronuclei and apoptosis
induction. Treatment of EMBS-exposed cells with the ROS scavenger, N-acetyl
cysteine, abrogated ROS production, cell cycle arrest and apoptosis implying an
essential role for ROS production in EMBS signaling. The inhibition of c-Jun N
terminal kinase (JNK) activity also inhibited EMBS-induced apoptosis suggesting
that EMBS triggers apoptosis via the JNK pathway. Lastly, evaluation of LC3IIB
protein levels indicated that autophagy is not activated in EMBS-exposed cells.
Our data shows that EMBS targets a pathway that leads to increased ROS production
as an early event that culminates in G2/M arrest and apoptosis by means of JNK
signaling in cancer cells. This study suggests a novel oxidative stress-dependent
mode of action for sulphamoylated derivatives.
PMID- 28410399
TI - Altered glucose metabolism and hypoxic response in alloxan-induced diabetic
atherosclerosis in rabbits.
AB - Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular
events. Several metabolic pathways are considered to contribute to the
development of atherosclerosis, but comprehensive metabolic alterations to
atherosclerotic arterial cells remain unknown. The present study investigated
metabolic changes and their relationship to vascular histopathological changes in
the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic
atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan
(100 mg/kg), injuring the arteries using a balloon, and feeding with a 0.5%
cholesterol diet. We histologically assessed the atherosclerotic lesion
development, cellular content, pimonidazole positive-hypoxic area, the nuclear
localization of hypoxia-inducible factor-1alpha, and apoptosis. We evaluated
comprehensive arterial metabolism by performing metabolomic analyses using
capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose
uptake and its relationship to vascular hypoxia using 18F-fluorodeoxyglucose and
pimonidazole. Plaque burden, macrophage content, and hypoxic areas were more
prevalent in arteries with diabetic, than non-diabetic atherosclerosis.
Metabolomic analyses highlighted 12 metabolites that were significantly altered
between diabetic and non-diabetic atherosclerosis. A half of them were associated
with glycolysis metabolites, and their levels were decreased in diabetic
atherosclerosis. The uptake of glucose evaluated as 18F-fluorodeoxyglucose in
atherosclerotic lesions increased according to increased macrophage content or
hypoxic areas in non-diabetic, but not diabetic rabbits. Despite profound hypoxic
areas, the nuclear localization of hypoxia-inducible factor-1alpha decreased and
the number of apoptotic cells increased in diabetic atherosclerotic lesions.
Altered glycolysis metabolism and an impaired response to hypoxia in
atherosclerotic lesions under conditions of insulin-dependent diabetes might be
involved in the development of diabetic atherosclerosis.
PMID- 28410400
TI - Inherited variants in genes somatically mutated in thyroid cancer.
AB - BACKGROUND: Tumour suppressor genes when mutated in the germline cause various
cancers, but they can also be somatically mutated in sporadic tumours. We
hypothesized that there may also be cancer-related germline variants in the genes
commonly mutated in sporadic well-differentiated thyroid cancer (WDTC). METHODS:
We performed a two-stage case-control association study with a total of 2214
cases and 2108 healthy controls from an Italian population. By genotyping 34
single nucleotide polymorphisms (SNPs), we covered a total of 59 missense SNPs
and SNPs located in the 5' and 3' untranslated regions (UTRs) of 10 different
genes. RESULTS: The Italian1 series showed a suggestive association for 8 SNPs,
from which three were replicated in the Italian2 series. The meta-analysis
revealed a study-wide significant association for rs459552 (OR: 0.84, 95%CI: 0.75
0.94) and rs1800900 (OR: 1.15, 95%CI: 1.05-1.27), located in the APC and GNAS
genes, respectively. The APC rs459552 is a missense SNP, located in a conserved
amino acid position, but without any functional consequences. The GNAS rs1800900
is located at a conserved 5'UTR and according to the experimental ENCODE data it
may affect promoter and histone marks in different cell types. CONCLUSIONS: The
results of this study yield new insights on WDTC, showing that inherited variants
in the APC and GNAS genes can play a role in the etiology of thyroid cancer.
Further studies are necessary to better understand the role of the identified
SNPs in the development of WDTC and to functionally validate our in silico
predictions.
PMID- 28410401
TI - RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A
virus infection.
AB - The type I interferon pathway plays a critical role in both host defense and
tolerance against viral infection and thus requires refined regulatory
mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti
viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus
(IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/-
mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral
load and heightened morbidity and mortality. Unexpectedly, this susceptibility
was linked to an inability of RIKP3-deficient macrophages (Mphi) to produce type
I IFN in the lungs of infected mice. In Mphi infected with IAV in vitro, we found
that RIPK3 regulates type I IFN both transcriptionally, by interacting with MAVS
and limiting RIPK1 interaction with MAVS, and post-transcriptionally, by
activating protein kinase R (PKR)-a critical regulator of IFN-beta mRNA
stability. Collectively, our findings indicate a novel role for RIPK3 in
regulating Mphi-mediated type I IFN anti-viral immunity, independent of its
conventional role in necroptosis.
PMID- 28410402
TI - Unexpected associated microalgal diversity in the lichen Ramalina farinacea is
uncovered by pyrosequencing analyses.
AB - The current literature reveals that the intrathalline coexistence of multiple
microalgal taxa in lichens is more common than previously thought, and additional
complexity is supported by the coexistence of bacteria and basidiomycete yeasts
in lichen thalli. This replaces the old paradigm that lichen symbiosis occurs
between a fungus and a single photobiont. The lichen Ramalina farinacea has
proven to be a suitable model to study the multiplicity of microalgae in lichen
thalli due to the constant coexistence of Trebouxia sp. TR9 and T. jamesii in
long-distance populations. To date, studies involving phycobiont diversity within
entire thalli are based on Sanger sequencing, but this method seems to
underestimate the diversity. Here, we aim to analyze both the microalgal
diversity and its community structure in a single thallus of the lichen R.
farinacea by applying a 454 pyrosequencing approach coupled with a careful ad hoc
performed protocol for lichen sample processing prior to DNA extraction. To
ascertain the reliability of the pyrosequencing results and the applied
bioinformatics pipeline results, the thalli were divided into three sections
(apical, middle and basal zones), and a mock community sample was used. The
developed methodology allowed 40448 filtered algal reads to be obtained from a
single lichen thallus, which encompassed 31 OTUs representative of different
microalgae genera. In addition to corroborating the coexistence of the two
Trebouxia sp. TR9 and T. jamesii taxa in the same thallus, this study showed a
much higher microalgal diversity associated with the lichen. Along the thallus
ramifications, we also detected variations in phycobiont distribution that might
correlate with different microenvironmental conditions. These results highlight
R. farinacea as a suitable material for studying microalgal diversity and further
strengthen the concept of lichens as multispecies microecosystems. Future
analyses will be relevant to ecophysiological and evolutionary studies to
understand the roles of the multiple photobionts in lichen symbioses.
PMID- 28410403
TI - Assessing gastroenterologist and patient acceptance of biosimilars in ulcerative
colitis and Crohn's disease across Germany.
AB - OBJECTIVES: This study examined gastroenterologists' motivation for prescribing
biosimilars, assessed their treatment preferences in relation to prescribing
behaviour, and explored patient attitudes to biosimilars. METHODS: Data were
taken from the Adelphi Real World Biosimilars Programme, a real-world, cross
sectional study undertaken in 2015-2016 with German gastroenterologists and
patients with ulcerative colitis or Crohn's disease. Gastroenterologists provided
data on their prescribing behaviour and attitudes towards biosimilars, and
invited the next eight eligible consecutive consulting patients to complete a
detailed questionnaire. For analysis, gastroenterologists were split into
'Investigative', 'Conservative', and 'Other' groups. RESULTS: Overall, 25
gastroenterologists and 136 patients participated. Biosimilars accounted for <15%
of all biologic therapies and >80% of gastroenterologists would prescribe a bio
originator rather than biosimilar as 1st line therapy if unrestricted. Patients
showed some reluctance to accept biosimilars, although of those receiving
biosimilars, 79% were satisfied with the current treatment of their condition,
and 69% were satisfied with the control of symptoms. Although at least 35% of
patients in each analysis group reported no concerns when starting treatment with
a bio-originator or biosimilar, 41% of previously biologic-naive patients
prescribed a biosimilar indicated potential side effects and potential long-term
problems, and 24% not knowing enough about the drug, as concerns. CONCLUSION:
Results demonstrate that there is reluctance from patients to accept biosimilars
and the need to further educate patients who are unsure to allow them to be
involved in decision making, highlighting the importance of patient and physician
communication. There remains a need for further research into non-clinical
switching and the long term impact of prescribing biosimilars.
PMID- 28410404
TI - Novel behavioral indicator of explicit awareness reveals temporal course of
frontoparietal neural network facilitation during motor learning.
AB - Deficits in sequential motor learning have been observed in many patient
populations. Having an understanding of the individual neural progression
associated with sequential learning in healthy individuals may provide valuable
insights for effective interventions with these patients. Due to individual
variability in motor skill acquisition, the temporal course of such learning will
be vary, suggesting a need for a more individualized approach. Knowing when a
subject becomes aware of movement patterns may provide a marker with which to
identify each individual's learning time course. To avoid interfering with the
incidental nature of discovery during learning, such an indicator requires an
indirect, behaviorally-based approach. In Part I, our study aimed to identify a
reliable behavioral indicator predictive of the presence of incidental explicit
awareness in a sequential motor learning task. Part II, utilized the predictive
indicator and EEG to provide neural validation of perceptual processing changes
temporally correlated with the indicator. Results of Part I provide a reliable
predictive indicator for the timing of explicit awareness development. Results
from Part II demonstrates strong classification reliability, as well as a
significant neural correlation with behavior for subjects developing awareness
(EXP), not observed with subjects without awareness (NOEXP). Additionally, a
temporal correlation of peak activation between neural regions was noted over
frontoparietal regions, suggesting that the incidental discovery of motor
patterns may involve a facilitative network during awareness development. The
proposed indicator provides a tool in which to further examine potential impacts
of awareness associated with incidental, or exploratory, motor learning, while
the individual nature of the indicator provides a tool for monitoring progress in
rehabilitative, exploratory motor learning paradigms.
PMID- 28410405
TI - Real-world treatment patterns for patients receiving second-line and third-line
treatment for advanced non-small cell lung cancer: A systematic review of
recently published studies.
AB - Most patients with advanced non-small cell lung cancer (NSCLC) have a poor
prognosis and receive limited benefit from conventional treatments, especially in
later lines of therapy. In recent years, several novel therapies have been
approved for second- and third-line treatment of advanced NSCLC. In light of
these approvals, it is valuable to understand the uptake of these new treatments
in routine clinical practice and their impact on patient care. A systematic
literature search was conducted in multiple scientific databases to identify
observational cohort studies published between January 2010 and March 2017 that
described second- or third-line treatment patterns and clinical outcomes in
patients with advanced NSCLC. A qualitative data synthesis was performed because
a meta-analysis was not possible due to the heterogeneity of the study
populations. A total of 12 different study cohorts in 15 articles were
identified. In these cohorts, single-agent chemotherapy was the most commonly
administered treatment in both the second- and third-line settings. In the 5
studies that described survival from the time of second-line treatment
initiation, median overall survival ranged from 4.6 months (95% CI, 3.8-5.7) to
12.8 months (95% CI, 10.7-14.5). There was limited information on the use of
biomarker-directed therapy in these patient populations. This systematic
literature review offers insights into the adoption of novel therapies into
routine clinical practice for second- and third-line treatment of patients with
advanced NSCLC. This information provides a valuable real-world context for the
impact of recently approved treatments for advanced NSCLC.
PMID- 28410406
TI - Lubiprostone improves intestinal permeability in humans, a novel therapy for the
leaky gut: A prospective randomized pilot study in healthy volunteers.
AB - BACKGROUND AND AIMS: The barrier function of the small intestinal mucosa prevents
the introduction of undesired pathogens into the body. Breakdown of this barrier
function increases intestinal permeability. This has been proposed to induce not
only gastrointestinal diseases, including inflammatory bowel disease and
irritable bowel syndrome, but also various other diseases, including allergies,
diabetes mellitus, liver diseases, and collagen diseases, which are associated
with this so called "leaky gut syndrome." As such, a method to prevent leaky gut
syndrome would have substantial clinical value. However, no drugs have been
demonstrated to improve disturbed intestinal permeability in humans to date.
Therefore, we investigated whether a drug used to treat chronic constipation,
lubiprostone, was effective for this purpose. METHODS: Healthy male volunteers
were treated with lubiprostone (24 MUg/day) for 28 days. Intestinal permeability
was evaluated by measuring the lactulose-mannitol ratio (LMR) after
administration of diclofenac and compared with an untreated group. The
examination was conducted three times in total, i.e., at baseline before
diclofenac administration and after 14 and 28 days of lubiprostone treatment.
Blood endotoxin activity was also evaluated at the same time points. RESULTS: The
final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14
in the untreated group). The LMR after 28 days of treatment was significantly
lower in the lubiprostone group than that in the untreated group (0.017 vs.
0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood
endotoxin activity exhibited almost no change over time in the lubiprostone and
untreated groups and displayed no significant differences at any time point of
examination. CONCLUSIONS: This study is the first to report an improvement in
leaky gut using an available drug in humans. The result suggests that
lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal
trial is needed to confirm our finding.
PMID- 28410407
TI - Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune
response via TLR2 and TLR9.
AB - Bacterial biofilms are associated with numerous human infections. The predominant
protein expressed in enteric biofilms is the amyloid curli, which forms highly
immunogenic complexes with DNA. Infection with curli-expressing bacteria or
systemic exposure to purified curli-DNA complexes triggers autoimmunity via the
generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies.
Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll
like receptor 9 (TLR9) through a two-step mechanism. First, the cross beta-sheet
structure of curli is bound by cell-surface Toll-like receptor 2 (TLR2), enabling
internalization of the complex into endosomes. After internalization, the curli
DNA immune complex binds strongly to endosomal TLR9, inducing production of type
I IFNs. Analysis of wild-type and TLR2-deficient macrophages showed that TLR2 is
the major receptor that drives the internalization of curli-DNA complexes.
Suppression of TLR2 internalization via endocytosis inhibitors led to a
significant decrease in Ifnbeta expression. Confocal microscopy analysis
confirmed that the TLR2-bound curli was required for shuttling of DNA to
endosomal TLR9. Structural analysis using small-angle X-ray scattering revealed
that incorporation of DNA into curli fibrils resulted in the formation of ordered
curli-DNA immune complexes. Curli organizes parallel, double-stranded DNA rods at
an inter-DNA spacing that matches up well with the steric size of TLR9. We also
found that production of anti-double-stranded DNA autoantibodies in response to
curli-DNA was attenuated in TLR2- and TLR9-deficient mice and in mice deficient
in both TLR2 and TLR9 compared to wild-type mice, suggesting that both innate
immune receptors are critical for shaping the autoimmune adaptive immune
response. We also detected significantly lower levels of interferon-stimulated
gene expression in response to purified curli-DNA in TLR2 and TLR9 deficient mice
compared to wild-type mice, confirming that TLR2 and TLR9 are required for the
induction of type I IFNs. Finally, we showed that curli-DNA complexes, but not
cellulose, were responsible elicitation of the immune responses to bacterial
biofilms. This study defines the series of events that lead to the severe pro
autoimmune effects of amyloid-expressing bacteria and suggest a mechanism by
which amyloid curli acts as a carrier to break immune tolerance to DNA, leading
to the activation of TLR9, production of type I IFNs, and subsequent production
of autoantibodies.
PMID- 28410409
TI - Correction: Rapid evolution of distinct Helicobacter pylori subpopulations in the
Americas.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1006546.].
PMID- 28410408
TI - Pleistocene climate changes shaped the population structure of Partamona
seridoensis (Apidae, Meliponini), an endemic stingless bee from the Neotropical
dry forest.
AB - Partamona seridoensis is an endemic stingless bee from the Caatinga, a
Neotropical dry forest in northeastern Brazil. Like other stingless bees, this
species plays an important ecological role as a pollinator. The aim of the
present study was to investigate the genetic structure and evolutionary history
of P. seridoensis across its current geographic range. Workers from 84 nests from
17 localities were analyzed for COI and Cytb genic regions. The population
structure tests (Bayesian phylogenetic inference, AMOVA and haplotype network)
consistently characterized two haplogroups (northwestern and eastern), with
little gene flow between them, generating a high differentiation between them as
well as among the populations within each haplogroup. The Mantel test revealed no
isolation by distance. No evidence of a potential geographic barrier in the
present that could explain the diversification between the P. seridoensis
haplogroups was found. However, Pleistocene climatic changes may explain this
differentiation, since the initial time for the P. seridoensis lineages
diversification took place during the mid-Pleistocene, specifically the
interglacial period, when the biota is presumed to have been more associated with
dry conditions and had more restricted, fragmented geographical distribution.
This event may have driven diversification by isolating the two haplogroups.
Otherwise, the climatic changes in the late Pleistocene must not have drastically
affected the population dynamics of P. seridoensis, since the Bayesian Skyline
Plot did not reveal any substantial fluctuation in effective population size in
either haplogroup. Considering its importance and the fact that it is an endemic
bee from a very threatened Neotropical dry forest, the results herein could be
useful to the development of conservation strategies for P. seridoensis.
PMID- 28410410
TI - Diabetes mellitus in patients with chronic obstructive pulmonary disease-The
impact on mortality.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the leading cause of
morbidity and mortality worldwide. There is evidence to support a connection
between COPD and diabetes mellitus (DM), another common medical disorder.
However, additional research is required to improve our knowledge of these
relationships and their possible implications. In this study, we investigated the
impact of DM on patient outcomes through the clinical course of COPD. METHODS: We
conducted a cohort study in patients from the Taiwan Longitudinal Health
Insurance Database between 2000 and 2013. Patients with COPD were identified and
assessed for pre-existing and incident DM. A Cox proportional hazards model was
built to identify factors associated with incident DM and to explore the
prognostic effects of DM on COPD patients. A propensity score method was used to
match COPD patients with incident DM to controls without incident DM. RESULTS:
Pre-existing DM was present in 332 (16%) of 2015 COPD patients who had a
significantly higher hazard ratio (HR) [1.244, 95% confidence interval (CI) 1.010
1.532] for mortality than that of the COPD patients without pre-existing DM.
During the 10-year follow-up period, 304 (19%) of 1568 COPD patients developed
incident DM; comorbid hypertension (HR, 1.810; 95% CI, 1.363-2.403),
cerebrovascular disease (HR, 1.517; 95% CI, 1.146-2.008) and coronary artery
disease (HR, 1.408; 95% CI 1.089-1.820) were significant factors associated with
incident DM. Survival was worse for the COPD patients with incident DM than for
the matched controls without incident DM (Log-rank, p = 0.027). CONCLUSIONS: DM,
either pre-existing or incident, was associated with worse outcomes in COPD
patients. Targeted surveillance and management of DM may be important in clinical
care of the COPD population.
PMID- 28410411
TI - Hepatitis C virus impairs natural killer cell activity via viral serine protease
NS3.
AB - Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic
cases owing to the impairment of innate and adaptive immune responses. The
modulation of natural killer (NK) cell functions by HCV leads to an impaired
innate immune response. However, the underling mechanisms and roles of HCV
proteins in this immune evasion are controversial, especially in the early phase
of HCV infection. To investigate the role of HCV nonstructural proteins
especially NS3 in the impairment of NK functions, NK cells were isolated from the
PBMCs by negative selection. To assess the direct cytotoxicity and IFN-gamma
production capability of NK cells, co-cultured with uninfected, HCV-infected, HCV
NS3 DNA-transfected Huh-7.5, or HCV-NS replicon cells. To determine the effect of
an NS3 serine protease inhibitor, HCV-infected Huh-7.5 cells were treated with
BILN-2061. Then, NK cells were harvested and further co-cultured with K-562
target cells. NK cell functions were analyzed by flow cytometry and enzyme-linked
immunosorbent assay. When co-cultured with HCV-infected Huh-7.5 cells, the
natural cytotoxicity and IFN-gamma production capability of NK cells were
significantly reduced. NK cell functions were inhibited to similar levels upon co
culture with HCV-NS replicon cells, NS3-transfected cells, and HCV-infected Huh
7.5 cells. These reductions were restored by BILN-2061-treatment. Furthermore,
BILN-2061-treatment significantly increased degranulation against K-562 target
cells and IFN-gamma productivity in NK cells. Consistent with these findings, the
expression levels of activating NK cell receptors, such as NKp46 and NKp30, were
also increased. In HCV-infected cells, the serine protease NS3 may play a role in
the abrogation of NK cell functions in the early phase of infection through
downregulation of NKp46 and NKp30 receptors on NK cells. Together, these results
suggest that NS3 represents a novel drug target for the treatment of HCV
infections.
PMID- 28410412
TI - Mycobacterium ulcerans low infectious dose and mechanical transmission support
insect bites and puncturing injuries in the spread of Buruli ulcer.
AB - Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is
a World Health Organization priority. In Australia, we have observed an
association between mosquitoes harboring the causative agent, Mycobacterium
ulcerans, and BU. Here we tested a contaminated skin model of BU transmission by
dipping the tails from healthy mice in cultures of the causative agent,
Mycobacterium ulcerans. Tails were exposed to mosquito (Aedes notoscriptus and
Aedes aegypti) blood feeding or punctured with sterile needles. Two of 12 of mice
with M. ulcerans contaminated tails exposed to feeding A. notoscriptus mosquitoes
developed BU. There were no mice exposed to A. aegypti that developed BU. Eighty
eight percent of mice (21/24) subjected to contaminated tail needle puncture
developed BU. Mouse tails coated only in bacteria did not develop disease. A
median incubation time of 12 weeks, consistent with data from human infections,
was noted. We then specifically tested the M. ulcerans infectious dose-50 (ID50)
in this contaminated skin surface infection model with needle puncture and
observed an ID50 of 2.6 colony-forming units. We have uncovered a biologically
plausible mechanical transmission mode of BU via natural or anthropogenic skin
punctures.
PMID- 28410413
TI - Validation of enhanced kinect sensor based motion capturing for gait assessment.
AB - Optical motion capturing systems are expensive and require substantial dedicated
space to be set up. On the other hand, they provide unsurpassed accuracy and
reliability. In many situations however flexibility is required and the motion
capturing system can only temporarily be placed. The Microsoft Kinect v2 sensor
is comparatively cheap and with respect to gait analysis promising results have
been published. We here present a motion capturing system that is easy to set up,
flexible with respect to the sensor locations and delivers high accuracy in gait
parameters comparable to a gold standard motion capturing system (VICON).
Further, we demonstrate that sensor setups which track the person only from one
side are less accurate and should be replaced by two-sided setups. With respect
to commonly analyzed gait parameters, especially step width, our system shows
higher agreement with the VICON system than previous reports.
PMID- 28410414
TI - Phthalate exposure and reproductive hormones and sex-hormone binding globulin
before puberty - Phthalate contaminated-foodstuff episode in Taiwan.
AB - BACKGROUND: In May 2011, a major incident involving phthalates-contaminated
foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to
foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements.
Concerns arose that normal pubertal development, especially reproductive hormone
regulation in children, could be disrupted by DEHP exposure. OBJECTIVE: To
investigate the association between phthalate exposure and reproductive hormone
levels among children following potential exposure to phthalate-tainted
foodstuffs. METHODS: A total of 239 children aged <12 years old were recruited
from 3 hospitals in north, central, and south Taiwan after the episode.
Structured questionnaires were used to collect the frequency and quantity of
exposures to 5 categories of phthalate-contaminated foodstuffs to assess
phthalate exposure in children. Urine samples were collected for the measurement
of phthalate metabolites. The estimated daily intake of DEHP exposure at the time
of the contamination incident occurred was calculated using both questionnaire
data and urinary DEHP metabolite concentrations. Multiple regression analyses
were applied to assess associations between phthalate exposure and reproductive
hormone levels in children. RESULTS: After excluding children with missing data
regarding exposure levels and hormone concentrations and girls with menstruation,
222 children were included in the statistical analyses. After adjustment for age
and birth weight, girls with above median levels of urinary mono-(2-ethyl-5
hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2
ethylhexyl) phthalate concentrations had higher odds of above median follicle
stimulating hormone concentrations. Girls with above median estimated average
daily DEHP exposures following the contamination episode also had higher odds of
sex hormone-binding globulin above median levels. CONCLUSIONS: Phthalate exposure
was associated with alterations of reproductive hormone levels in girls.
PMID- 28410415
TI - Influence of host factors and parasite biomass on the severity of imported
Plasmodium falciparum malaria.
AB - OBJECTIVES: Imported malaria in France is characterized by various clinical
manifestations observed in a heterogeneous population of patients such as
travelers/expatriates and African migrants. In this population, host factors and
parasite biomass associated with severe imported malaria are poorly known.
METHODS: From data collected by the Centre National de Reference du Paludisme, we
identified epidemiological, demographic and biological features including
parasite biomass and anti-plasmodial antibody levels (negative, positive and
strongly positive serology) associated with different disease severity groups
(very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological
groups (travelers/expatriates, first- and second-generation migrants). RESULTS:
Age, ethnicity, absence of prior infection with P. falciparum, antibody levels,
plasma PfHRP2 levels, total and circulating parasite biomass were related to
severe malaria onset. Sequestered parasite biomass tended to be increased in very
severe malaria, and was strongly correlated to the antibody level of the host.
CONCLUSIONS: Prior exposure to P. falciparum is associated with high anti
plasmodial antibody levels which influence clinical presentation of imported
malaria and its correlated circulating and sequestered parasite burden.
PMID- 28410416
TI - Correction: A Year of Infection in the Intensive Care Unit: Prospective Whole
Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions
and Novel Microbiota.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1005413.].
PMID- 28410417
TI - Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non
small cell lung cancer in a Chinese Han population.
AB - Non-small cell lung cancer is one of the most common cancers and the leading
cause of cancer death worldwide. Genetic variants in regulatory regions of some
miRNAs might be involved in non-small cell lung cancer susceptibility and
survival. rs12220909 (G/C) genetic polymorphism in miR-4293 has been shown to be
associated with decreased risk of esophageal squamous cell carcinoma. However,
the influence of rs12220909 genetic variation on non-small cell lung cancer
susceptibility has not been reported. In order to evaluate the potential
association between miR-4293 rs12220909 and non-small cell lung cancer risk in a
Chinese population, we performed a case-control study among 998 non-small cell
lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was
significantly associated with decreased susceptibility to non-small cell lung
cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR
= 0.687, 95%CI = 0.564-0.837, P = 1.95E-4), which indicates that rs12220909 in
miR-4293 may play a significant role in the development of non-small cell lung
cancer.
PMID- 28410418
TI - Heterogeneous firing responses predict diverse couplings to presynaptic activity
in mice layer V pyramidal neurons.
AB - In this study, we present a theoretical framework combining experimental
characterizations and analytical calculus to capture the firing rate input-output
properties of single neurons in the fluctuation-driven regime. Our framework
consists of a two-step procedure to treat independently how the dendritic input
translates into somatic fluctuation variables, and how the latter determine
action potential firing. We use this framework to investigate the functional
impact of the heterogeneity in firing responses found experimentally in young
mice layer V pyramidal cells. We first design and calibrate in vitro a simplified
morphological model of layer V pyramidal neurons with a dendritic tree following
Rall's branching rule. Then, we propose an analytical derivation for the membrane
potential fluctuations at the soma as a function of the properties of the
synaptic input in dendrites. This mathematical description allows us to easily
emulate various forms of synaptic input: either balanced, unbalanced,
synchronized, purely proximal or purely distal synaptic activity. We find that
those different forms of dendritic input activity lead to various impact on the
somatic membrane potential fluctuations properties, thus raising the possibility
that individual neurons will differentially couple to specific forms of activity
as a result of their different firing response. We indeed found such a
heterogeneous coupling between synaptic input and firing response for all types
of presynaptic activity. This heterogeneity can be explained by different levels
of cellular excitability in the case of the balanced, unbalanced, synchronized
and purely distal activity. A notable exception appears for proximal dendritic
inputs: increasing the input level can either promote firing response in some
cells, or suppress it in some other cells whatever their individual excitability.
This behavior can be explained by different sensitivities to the speed of the
fluctuations, which was previously associated to different levels of sodium
channel inactivation and density. Because local network connectivity rather
targets proximal dendrites, our results suggest that this aspect of biophysical
heterogeneity might be relevant to neocortical processing by controlling how
individual neurons couple to local network activity.
PMID- 28410419
TI - The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis
following a multicentre randomised controlled trial.
AB - OBJECTIVE: Reducing perinatal morbidity and mortality is one of the major
challenges in modern health care. Analysing the ST segment of the fetal
electrocardiogram was thought to be the breakthrough in fetal monitoring during
labour. However, its implementation in clinical practice yields many false alarms
and ST monitoring is highly dependent on cardiotocogram assessment, limiting its
value for the prediction of fetal distress during labour. This study aims to
evaluate the relation between physiological variations in the orientation of the
fetal electrical heart axis and the occurrence of ST events. METHODS: A post-hoc
analysis was performed following a multicentre randomised controlled trial,
including 1097 patients from two participating centres. All women were monitored
with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal
quality, missing blood gas analysis, and congenital heart disease were excluded.
The orientation of the fetal electrical heart axis affects the height of the
initial T/QRS baseline, and therefore the incidence of ST events. We grouped
tracings with the same initial baseline T/QRS value. We depicted the number of ST
events as a function of the initial baseline T/QRS value with a linear regression
model. RESULTS: A significant increment of ST events was observed with increasing
height of the initial T/QRS baseline, irrespective of the fetal condition;
correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12.
CONCLUSION: The orientation of the fetal electrical heart axis and accordingly
the height of the initial T/QRS baseline should be taken into account in fetal
monitoring with ST analysis.
PMID- 28410420
TI - Comparison of cell-based assays for the identification and evaluation of
competitive CXCR4 inhibitors.
AB - The chemokine receptor CXCR4 is activated by its unique chemokine ligand CXCL12
and regulates many physiological and developmental processes such as
hematopoietic cell trafficking. CXCR4 is also one of the main co-receptors for
human immunodeficiency virus (HIV) entry. Dysfunction of the CXCL12/CXCR4 axis
contributes to several human pathologies, including cancer and inflammatory
diseases. Consequently, inhibition of CXCR4 activation is recognized as an
attractive target for therapeutic intervention. In this regard, numerous agents
modifying CXCR4 activity have been evaluated in in vitro experimental studies and
pre-clinical models. Here, we evaluated a CXCL12 competition binding assay for
its potential as a valuable initial screen for functional and competitive CXCR4
inhibitors. In total, 11 structurally diverse compounds were included in a side
by-side comparison of in vitro CXCR4 cell-based assays, such as CXCL12
competition binding, CXCL12-induced calcium signaling, CXCR4 internalization,
CXCL12-guided cell migration and CXCR4-specific HIV-1 replication experiments.
Our data indicated that agents that inhibit CXCL12 binding, i.e. the anti-CXCR4
peptide analogs T22, T140 and TC14012 and the small molecule antagonists AMD3100,
AMD3465, AMD11070 and IT1t showed inhibitory activity with consistent relative
potencies in all further applied CXCR4-related assays. Accordingly, agents
exerting no or very weak receptor binding (i.e., CTCE-9908, WZ811, Me6TREN and
gambogic acid) showed no or very poor anti-CXCR4 inhibitory activity. Thus,
CXCL12 competition binding studies were proven to be highly valuable as an
initial screening assay and indicative for the pharmacological and functional
profile of competitive CXCR4 antagonists, which will help the design of new
potent CXCR4 inhibitors.
PMID- 28410421
TI - phylo-node: A molecular phylogenetic toolkit using Node.js.
AB - BACKGROUND: Node.js is an open-source and cross-platform environment that
provides a JavaScript codebase for back-end server-side applications. JavaScript
has been used to develop very fast and user-friendly front-end tools for
bioinformatic and phylogenetic analyses. However, no such toolkits are available
using Node.js to conduct comprehensive molecular phylogenetic analysis. RESULTS:
To address this problem, I have developed, phylo-node, which was developed using
Node.js and provides a stable and scalable toolkit that allows the user to
perform diverse molecular and phylogenetic tasks. phylo-node can execute the
analysis and process the resulting outputs from a suite of software options that
provides tools for read processing and genome alignment, sequence retrieval,
multiple sequence alignment, primer design, evolutionary modeling, and phylogeny
reconstruction. Furthermore, phylo-node enables the user to deploy server
dependent applications, and also provides simple integration and interoperation
with other Node modules and languages using Node inheritance patterns, and a
customized piping module to support the production of diverse pipelines.
CONCLUSIONS: phylo-node is open-source and freely available to all users without
sign-up or login requirements. All source code and user guidelines are openly
available at the GitHub repository: https://github.com/dohalloran/phylo-node.
PMID- 28410422
TI - Diversity of Algerian oases date palm (Phoenix dactylifera L., Arecaceae):
Heterozygote excess and cryptic structure suggest farmer management had a major
impact on diversity.
AB - Date palm (Phoenix dactyliferaL.) is the mainstay of oasis agriculture in the
Saharan region. It is cultivated in a large part of the Mediterranean coastal
area of the Sahara and in most isolated oases in the Algerian desert. We sampled
10 oases in Algeria to understand the structure of date palm diversity from the
coastal area to a very isolated desert location. We used 18 microsatellite
markers and a chloroplast minisatellite to characterize 414 individual palm trees
corresponding to 114 named varieties. We found a significant negative inbreeding
coefficient, suggesting active farmer selection for heterozygous individuals.
Three distinct genetic clusters were identified, a ubiquitous set of varieties
found across the different oases, and two clusters, one of which was specific to
the northern area, and the other to the drier southern area of the Algerian
Sahara. The ubiquitous cluster presented very striking chloroplast diversity,
signing the frequency of haplotypes found in Saudi Arabia, the most eastern part
of the date palm range. Exchanges of Middle Eastern and Algerian date palms are
known to have occurred and could have led to the introduction of this particular
chlorotype. However, Algerian nuclear diversity was not of eastern origin. Our
study strongly suggests that the peculiar chloroplastic diversity of date palm is
maintained by farmers and could originate from date palms introduced from the
Middle East a long time ago, which since then, hasbeen strongly introgressed.
This study illustrates the complex structure of date palm diversity in Algerian
oases and the role of farmers in shaping such cryptic diversity.
PMID- 28410424
TI - Trends in the prevalence and management of pre-stroke atrial fibrillation, the
South London Stroke Register, 1995-2014.
AB - BACKGROUND: Previous studies have found low use of anticoagulation prior to
stroke, in people with atrial fibrillation (AF). This study examined data on
patients with AF-related stroke from a population-based stroke register, and
sought to examine changes in management of AF prior to stroke, and reasons for
suboptimal treatment, in those who were known to be at a high risk of stroke.
METHODS: The South London Stroke Register (SLSR) is an ongoing population-based
register recording first-in-a-lifetime stroke. Trends in the prevalence of AF,
and antithrombotic medication prescribed before the stroke, were investigated
from 1995 to 2014. Multivariable logistic regression analyses were conducted to
assess the factors associated with appropriate management. RESULTS: Of the 5041
patients on the register, 816 (16.2%) were diagnosed with AF before their stroke.
AF related stroke increased substantially among Black Carribean and Black African
patients, comprising 5% of the overall cohort in 1995-1998, increasing to 25% by
2011-2014 (p<0.001). Anticoagulant prescription in AF patients at high-risk of
stroke (CHADS2 score [> = 2]) increased from 9% (1995-1998) to 30% (2011-2014)
(p<0.001). Antiplatelet prescription was more commonly prescribed throughout all
time periods (43% to 64% of high-risk patients.) Elderly patients (>65) were
significantly less likely to be prescribed an anticoagulant, with ethnicity,
gender and deprivation showing no association with anticoagulation. CONCLUSIONS:
Most AF-related strokes occurred in people who could have been predicted to be at
high risk before their stroke, yet were not prescribed optimal preventative
treatment. The elderly,despite being at highest stroke risk, were rarely
prescribed anticoagulants.
PMID- 28410425
TI - The cobas(r) HCV GT is a new tool that accurately identifies Hepatitis C virus
genotypes for clinical practice.
AB - OBJECTIVE: We aimed to evaluate the correct assignment of HCV genotype/subtypes
1a and 1b by cobas(r) HCV genotyping (GT) assay (Roche Molecular Diagnostics)
compared with nonstructural protein 5B (NS5B) sequencing. PATIENTS AND METHODS:
Clinical samples from 153 patients submitted for HCV genotyping were studied.
After genotyping with the cobas(r) HCV GT, sequencing of a 387 bp fragment in the
NS5B gene and phylogenetic analysis was employed to compare genotyping results.
Major discrepancies were defined as differences in the assigned genotype by
cobas(r) HCV GT and NS5B sequencing (including genotype 1 subtypes 1a and 1b
misclassification). RESULTS: Overall agreement between the cobas(r) HCV GT and
NS5B sequencing was 98%; all the 1a, 1b, 2, 3 and 4 genotypes identified by
cobas(r) HCV GT were concordant with NS5B sequencing. Three samples tested
"indetermined" by cobas(r) HCV GT assay and were genotyped as 1a, 3a, and 4d by
NS5B sequencing. CONCLUSSION: These results indicate that the cobas(r) HCV GT
assay correctly identifies HCV genotypes, and points out the importance of
additional methods based on DNA sequencing for resolving indeterminate results.
PMID- 28410423
TI - DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control
of germline stem cell proliferation.
AB - Under replete growth conditions, abundant nutrient uptake leads to the systemic
activation of insulin/IGF-1 signalling (IIS) and the promotion of stem cell
growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the
activation of which also supports optimal stem cell proliferation in various
systems. Stem cell proliferation rates can further be locally refined to meet the
resident tissue's need for differentiated progeny. We have recently shown that
the accumulation of mature oocytes in the C. elegans germ line, through DAF
18/PTEN, inhibits adult germline stem cell (GSC) proliferation, despite high
systemic IIS activation. We show here that this feedback occurs through a novel
cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3
to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC
proliferation and the production of additional oocytes. Interestingly, our
results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in
the absence of apparent energy stress. As all components are conserved, similar
signalling cascades may regulate stem cell activities in other organisms and be
widely implicated in cancer.
PMID- 28410426
TI - Factors affecting human colostrum fatty acid profile: A case study.
AB - The role of maternal colostrum to infant development has been extensively studied
and presented. Among the main factors which contribute to breast milk composition
are maternal diet, age and body mass index, parity, duration of pregnancy and
stage of lactation. This study aims to investigate the potential impact of
several factors including demographic (i.e. maternal age and nationality) on the
colostrum fatty acid profile. Colostrum was collected the third day postpartum in
a Greek maternity hospital. Certain lipid quality indices and fatty acid ratios
were estimated and results were statistically processed. The main identified
fatty acids were palmitic (C16:0), oleic (C18:1omega-9), and linoleic (C18:2omega
6) acids. Among fatty acids, saturated fatty acids predominated (47.61%),
followed by monounsaturated fatty acids (39.26%), while polyunsaturated fatty
acids had the lowest proportion (13.13%). Values of lipid quality indices were
within the reported in the literature ranges. Maternal body mass index,
nationality, age, mode of delivery, gender and fetal weight percentile were
studied in respect to their potential influence on the fatty acid profile of
colostrum fat. Results suggest that colostrum fatty acid profile was mainly
dependent on maternal nationality and age rather than mode of delivery and
maternal BMI. Regarding the effect of maternal nationality, significant
differences were found for saturated and monounsaturated fatty acids. Of the most
interesting findings is that colostrum fat from older (>=35 years) mothers had
less saturated fat and more appropriate LQIs values. Finally, a reversed
correlation was observed between the customized centile of the infants and the
colostrum fat content.
PMID- 28410427
TI - TCR stimulation strength is inversely associated with establishment of functional
brain-resident memory CD8 T cells during persistent viral infection.
AB - Establishing functional tissue-resident memory (TRM) cells at sites of infection
is a newfound objective of T cell vaccine design. To directly assess the impact
of antigen stimulation strength on memory CD8 T cell formation and function
during a persistent viral infection, we created a library of mouse polyomavirus
(MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that
exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By
altering a subdominant epitope in a nonstructural viral protein and monitoring
memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice,
we circumvented potentially confounding changes in viral infection levels, virus
associated inflammation, size of the immunodominant virus-specific CD8 T cell
response, and shifts in TCR affinity that may accompany temporal recruitment of
endogenous polyclonal cells. Using this strategy, we found that antigen
stimulation strength was inversely associated with the function of memory CD8 T
cells during a persistent viral infection. We further show that CD8 TRM cells
recruited to the brain following systemic infection with viruses expressing
epitopes with suboptimal stimulation strength respond more efficiently to
challenge CNS infection with virus expressing cognate antigen. These data
demonstrate that the strength of antigenic stimulation during recruitment of CD8
T cells influences the functional integrity of TRM cells in a persistent viral
infection.
PMID- 28410429
TI - Bayesian methods for jointly estimating genomic breeding values of one continuous
and one threshold trait.
AB - Genomic selection has become a useful tool for animal and plant breeding.
Currently, genomic evaluation is usually carried out using a single-trait model.
However, a multi-trait model has the advantage of using information on the
correlated traits, leading to more accurate genomic prediction. To date, joint
genomic prediction for a continuous and a threshold trait using a multi-trait
model is scarce and needs more attention. Based on the previously proposed
methods BayesCpi for single continuous trait and BayesTCpi for single threshold
trait, we developed a novel method based on a linear-threshold model, i.e., LT
BayesCpi, for joint genomic prediction of a continuous trait and a threshold
trait. Computing procedures of LT-BayesCpi using Markov Chain Monte Carlo
algorithm were derived. A simulation study was performed to investigate the
advantages of LT-BayesCpi over BayesCpi and BayesTCpi with regard to the accuracy
of genomic prediction on both traits. Factors affecting the performance of LT
BayesCpi were addressed. The results showed that, in all scenarios, the accuracy
of genomic prediction obtained from LT-BayesCpi was significantly increased for
the threshold trait compared to that from single trait prediction using
BayesTCpi, while the accuracy for the continuous trait was comparable with that
from single trait prediction using BayesCpi. The proposed LT-BayesCpi could be a
method of choice for joint genomic prediction of one continuous and one threshold
trait.
PMID- 28410428
TI - TUFT1, a novel candidate gene for metatarsophalangeal osteoarthritis, plays a
role in chondrogenesis on a calcium-related pathway.
AB - Osteoarthritis (OA) is the most common degenerative joint disorder and genetic
factors have been shown to have a significant role in its etiology. The first
metatarsophalangeal joint (MTP I) is highly susceptible to development of OA due
to repetitive mechanical stress during walking. We used whole exome sequencing to
study genetic defect(s) predisposing to familial early-onset bilateral MTP I OA
inherited in an autosomal dominant manner. A nonsynonymous single nucleotide
variant rs41310883 (c.524C>T, p.Thr175Met) in TUFT1 gene was found to co
segregate perfectly with MTP I OA. The role of TUFT1 and the relevance of the
identified variant in pathogenesis of MTP I OA were further assessed using
functional in vitro analyses. The variant reduced TUFT1 mRNA and tuftelin protein
expression in HEK293 cells. ATDC5 cells overexpressing wild type (wt) or mutant
TUFT1 were cultured in calcifying conditions and chondrogenic differentiation was
found to be inhibited in both cell populations, as indicated by decreased marker
gene expression when compared with the empty vector control cells. Also, the
formation of cartilage nodules was diminished in both TUFT1 overexpressing ATDC5
cell populations. At the end of the culturing period the calcium content of the
extracellular matrix was significantly increased in cells overexpressing mutant
TUFT1 compared to cells overexpressing wt TUFT1 and control cells, while the
proteoglycan content was reduced. These data imply that overexpression of TUFT1
in ATDC5 inhibits chondrogenic differentiation, and the identified variant may
contribute to the pathogenesis of OA by increasing calcification and reducing
amount of proteoglycans in the articular cartilage extracellular matrix thus
making cartilage susceptible for degeneration and osteophyte formation.
PMID- 28410431
TI - The effect of foetal growth restriction on the development of migraine and
tension-type headache in adulthood. The HUNT Study.
AB - BACKGROUND: There is little knowledge about how factors early in life affect the
development of migraine and tension-type headache. We aimed to examine whether
growth restriction in utero is associated with development of migraine and
frequent tension-type headache in adults. METHODS: The population-based Nord
Trondelag Health Study (HUNT 3) contained a validated headache questionnaire,
which differentiated between migraine and tension-type headache. These data were
linked to information on weight and gestational age at birth from the Norwegian
Medical Birth Registry. In total 4557 females and 2789 males, aged 19-41 years,
were included in this registry-based study. Participants were categorized as
appropriate for gestational age (AGA, 10th-90th percentile), small for
gestational age (SGA, 3rd-10th percentile) or very small for gestational age
(VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios
(OR) with 95% confidence intervals (CI) for migraine and tension-type headache,
with exposure being growth restriction at birth. RESULTS: The effect of growth
restriction on migraine was modified by sex, with a significant association in
males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA
were at increased risk of developing migraine (OR 2.73, 95% CI 1.63-4.58,
p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96
2.35, p = 0.08) compared to those born AGA. There was no significant association
between growth restriction and frequent TTH (p = 0.051). CONCLUSION: Growth
restriction was associated with increased risk of migraine in adulthood among
males, but not among females. This suggests that migraine might, in part, be
influenced by early life events, and that males seem to be particularly
vulnerable.
PMID- 28410432
TI - Patterns of orchid bee species diversity and turnover among forested plateaus of
central Amazonia.
AB - The knowledge of spatial pattern and geographic beta-diversity is of great
importance for biodiversity conservation and interpreting ecological information.
Tropical forests, especially the Amazon Rainforest, are well known for their high
species richness and low similarity in species composition between sites, both at
local and regional scales. We aimed to determine the effect and relative
importance of area, isolation and climate on species richness and turnover in
orchid bee assemblages among plateaus in central Brazilian Amazonia. Variance
partitioning techniques were applied to assess the relative effects of spatial
and environmental variables on bee species richness, phylogeny and composition.
We hypothesized that greater abundance and richness of orchid bees would be found
on larger plateaus, with a set of core species occurring on all of them. We also
hypothesized that smaller plateaus would possess lower phylogenetic diversity. We
found 55 bee species distributed along the nine sampling sites (plateaus) with 17
of them being singletons. There was a significant decrease in species richness
with decreasing size of plateaus, and a significant decrease in the similarity in
species composition with greater distance and climatic variation among sampling
sites. Phylogenetic diversity varied among the sampling sites but was directly
related to species richness. Although not significantly related to plateau area,
smaller or larger PDFaith were observed in the smallest and the largest plateaus,
respectively.
PMID- 28410430
TI - Caste-, sex-, and age-dependent expression of immune-related genes in a Japanese
subterranean termite, Reticulitermes speratus.
AB - Insects protect themselves from microbial infections through innate immune
responses, including pathogen recognition, phagocytosis, the activation of
proteolytic cascades, and the synthesis of antimicrobial peptides. Termites,
eusocial insects inhabiting microbe-rich wood, live in closely-related family
groups that are susceptible to shared pathogen infections. To resist pathogenic
infection, termite families have evolved diverse immune adaptations at both
individual and societal levels, and a strategy of trade-offs between reproduction
and immunity has been suggested. Although termite immune-inducible genes have
been identified, few studies have investigated the differential expression of
these genes between reproductive and neuter castes, and between sexes in each
caste. In this study, we compared the expression levels of immune-related genes
among castes, sexes, and ages in a Japanese subterranean termite, Reticulitermes
speratus. Using RNA-seq, we found 197 immune-related genes, including 40 pattern
recognition proteins, 97 signalling proteins, 60 effectors. Among these genes,
174 showed differential expression among castes. Comparing expression levels
between males and females in each caste, we found sexually dimorphic expression
of immune-related genes not only in reproductive castes, but also in neuter
castes. Moreover, we identified age-related differential expression of 162 genes
in male and/or female reproductives. In addition, although R. speratus is known
to use the antibacterial peptide C-type lysozyme as an egg recognition pheromone,
we determined that R. speratus has not only C-type, but also P-type and I-type
lysozymes, as well as other termite species. Our transcriptomic analyses revealed
immune response plasticity among all castes, and sex-biased expression of immune
genes even in neuter castes, suggesting a sexual division of labor in the immune
system of R. speratus. This study heightens the understanding of the evolution of
antimicrobial strategies in eusocial insects, and of sexual roles in insect
societies as a whole.
PMID- 28410433
TI - Simple biochemical networks allow accurate sensing of multiple ligands with a
single receptor.
AB - Cells use surface receptors to estimate concentrations of external ligands.
Limits on the accuracy of such estimations have been well studied for pairs of
ligand and receptor species. However, the environment typically contains many
ligands, which can bind to the same receptors with different affinities,
resulting in cross-talk. In traditional rate models, such cross-talk prevents
accurate inference of concentrations of individual ligands. In contrast, here we
show that knowing the precise timing sequence of stochastic binding and unbinding
events allows one receptor to provide information about multiple ligands
simultaneously and with a high accuracy. We show that such high-accuracy
estimation of multiple concentrations can be realized with simple structural
modifications of the familiar kinetic proofreading biochemical network diagram.
We give two specific examples of such modifications. We argue that structural and
functional features of real cellular biochemical sensory networks in immune
cells, such as feedforward and feedback loops or ligand antagonism, sometimes can
be understood as solutions to the accurate multi-ligand estimation problem.
PMID- 28410435
TI - Small area estimation of child undernutrition in Ethiopian woredas.
AB - Reducing child undernutrition is a key social policy objective of the Ethiopian
government. Despite substantial reduction over the last decade and a half, child
undernutrition is still high; with 48 percent of children either stunted,
underweight or wasted, undernutrition remains an important child health
challenge. The existing literature highlights that targeting of efforts to reduce
undernutrition in Ethiopia is inefficient, in part due to lack of data and
updated information. This paper remedies some of this shortfall by estimating
levels of stunting and underweight in each woreda for 2014. The estimates are
small area estimations based on the 2014 Demographic and Health Survey and the
latest population census. It is shown that small area estimations are powerful
predictors of undernutrition, even compared to household characteristics, such as
wealth and education, and hence a valuable targeting metric. The results show
large variations in share of children undernourished within each region, more
than between regions. The results also show that the locations with larger
challenges depend on the chosen undernutrition statistic, as the share, number
and concentration of undernourished children point to vastly different locations.
There is also limited correlation between share of children underweight and
stunted across woredas, indicating that different locations face different
challenges.
PMID- 28410434
TI - New function of aldoxime dehydratase: Redox catalysis and the formation of an
unexpected product.
AB - In general, hemoproteins are capable of catalyzing redox reactions. Aldoxime
dehydratase (OxdA), which is a unique heme-containing enzyme, catalyzes the
dehydration of aldoximes to the corresponding nitriles. Its reaction is a rare
example of heme directly activating an organic substrate, unlike the utilization
of H2O2 or O2 as a mediator of catalysis by other heme-containing enzymes. While
it is unknown whether OxdA catalyzes redox reactions or not, we here for the
first time detected catalase activity (which is one of the redox activities) of
wild-type OxdA, OxdA(WT). Furthermore, we constructed a His320 -> Asp mutant of
OxdA [OxdA(H320D)], and found it exhibits catalase activity. Determination of the
kinetic parameters of OxdA(WT) and OxdA(H320D) revealed that their Km values for
H2O2 were similar to each other, but the kcat value of OxdA(H320D) was 30 times
higher than that of OxdA(WT). Next, we examined another redox activity and found
it was the peroxidase activity of OxdAs. While both OxdA(WT) and OxdA(H320D)
showed the activity, the activity of OxdA(H320D) was dozens of times higher than
that of OxdA(WT). These findings demonstrated that the H320D mutation enhances
the peroxidase activity of OxdA. OxdAs (WT and H320D) were found to catalyze
another redox reaction, a peroxygenase reaction. During this reaction of
OxdA(H320D) with 1-methoxynaphthalene as a substrate, surprisingly, the reaction
mixture changed to a color different from that with OxdA(WT), which was due to
the known product, Russig's blue. We purified and identified the new product as 1
methoxy-2-naphthalenol, which has never been reported as a product of the
peroxygenase reaction, to the best of our knowledge. These findings indicated
that the H320D mutation not only enhanced redox activities, but also
significantly altered the hydroxylation site of the substrate.
PMID- 28410437
TI - 4-Cyanobenzenesulfonamides: Amine Synthesis and Protecting Strategy To Compliment
the Nosyl Group.
AB - 4-Cyanobenzenesulfonamides of secondary amines were found to cleave to the parent
amine cleanly under the action of thiol and base. This feature readily lends
itself to the use of this motif as an amine protecting/activating group within a
broader context of amine synthesis. The crystalline sulfonamides could be further
elaborated by alkylation and arylation similarly to nitrobenzenesulfonamides. The
sulfonamides could withstand conditions that functionalize nitroarenes, such as
reductions and vicarious nucleophilic substitution reactions.
PMID- 28410436
TI - Ocean acidification effects on mesozooplankton community development: Results
from a long-term mesocosm experiment.
AB - Ocean acidification may affect zooplankton directly by decreasing in pH, as well
as indirectly via trophic pathways, where changes in carbon availability or pH
effects on primary producers may cascade up the food web thereby altering
ecosystem functioning and community composition. Here, we present results from a
mesocosm experiment carried out during 113 days in the Gullmar Fjord, Skagerrak
coast of Sweden, studying plankton responses to predicted end-of-century pCO2
levels. We did not observe any pCO2 effect on the diversity of the
mesozooplankton community, but a positive pCO2 effect on the total
mesozooplankton abundance. Furthermore, we observed species-specific
sensitivities to pCO2 in the two major groups in this experiment, copepods and
hydromedusae. Also stage-specific pCO2 sensitivities were detected in copepods,
with copepodites being the most responsive stage. Focusing on the most abundant
species, Pseudocalanus acuspes, we observed that copepodites were significantly
more abundant in the high-pCO2 treatment during most of the experiment, probably
fuelled by phytoplankton community responses to high-pCO2 conditions.
Physiological and reproductive output was analysed on P. acuspes females through
two additional laboratory experiments, showing no pCO2 effect on females'
condition nor on egg hatching. Overall, our results suggest that the Gullmar
Fjord mesozooplankton community structure is not expected to change much under
realistic end-of-century OA scenarios as used here. However, the positive pCO2
effect detected on mesozooplankton abundance could potentially affect biomass
transfer to higher trophic levels in the future.
PMID- 28410438
TI - Effect of Lipoxygenase Oxidation on Surface Deposition of Unsaturated Fatty
Acids.
AB - We studied the interactions of lipid molecules (linoleic acid, glycerol
trilinoleate and a complex mixture of wood extractives) with hydrophilic and
hydrophobic surfaces (cellulose nanofibrils (CNFs) and polyethylene terephthalate
(PET), respectively). The effect of lipoxygenase treatment to minimize the
affinity of the lipids with the given surface was considered. Application of an
electroacoustic sensing technique (QCM) allowed the monitoring of the kinetics of
oxidation as well as dynamics of lipid deposition on CNF and PET. The effect of
the lipoxygenase enzymes (LOX) was elucidated with regards to their ability to
reduce the formation of soiling lipid layers. The results pointed to the fact
that the rate of colloidal oxidation depended on the type of lipid substrate. The
pretreatment of the lipids with LOX reduced substantially their affinity to the
surfaces, especially PET. Surface plasmon resonance (SPR) sensograms confirmed
the effect of oxidation in decreasing the extent of deposition on the hydrophilic
CNF. QCM energy dissipation analyses revealed the possible presence of a loosely
adsorbed lipid layer on the PET surface. The morphology of the deposits
accumulated on the solids was determined by atomic force microscopy and indicated
important changes upon lipid treatment with LOX. The results highlighted the
benefit of enzyme as a biobased treatment to reduce hydrophobic interactions,
thus providing a viable solution to the control of lipid deposition from aqueous
media.
PMID- 28410439
TI - Responses of Bacterial Communities to CuO Nanoparticles in Activated Sludge
System.
AB - The main objectives of this study were to investigate the influence of copper
oxide nanoparticles (CuO NPs) on wastewater nutrient removal, bacterial community
and molecular ecological network in activated sludge. The results showed that
long-term exposure to 1 mg/L CuO NPs induced an increase of effluent
concentrations of ammonia and total phosphorus, which was consistent with the
inhibition of enzyme activities of ammonia monooxygenase, nitrite oxidoreductase,
exopolyphosphatase, and polyphosphate in the presence of CuO NPs. MiSeq
sequencing data indicated that CuO NPs significantly decreased the bacterial
diversity and altered the overall bacterial community structure in activated
sludge. Some genera involved in nitrogen and phosphorus removal, such as
Nitrosomonas, Acinetobacter, and Pseudomonas decreased significantly. Molecular
ecological network analysis showed that network interactions among different
phylogenetic populations were markedly changed by CuO NPs. For example, beta
Proteobacteria, playing an important role in nutrients removal, had less complex
interactions in the presence of CuO NPs. These shifts of the abundance of related
genera, together with the network interactions may be associated with the
deterioration of ammonia and phosphorus removal. This study provides insights
into our understanding of shifts in the bacteria community and their molecular
ecological network under CuO NPs in activated sludge systems.
PMID- 28410440
TI - Control of Liposomal Penetration into Three-Dimensional Multicellular Tumor
Spheroids by Modulating Liposomal Membrane Rigidity.
AB - Effective penetration of drug-carrying nanoparticles into solid tumors is a major
challenge in cancer therapy. Exploration of the physicochemical properties of
nanoparticles that affect penetration efficiency is required to achieve maximum
therapeutic effects. Here, we used confocal laser scanning microscopy to evaluate
the efficiencies of penetration of fluorescently labeled liposomes into three
dimensional spheroids composed of HeLa cells. The prepared liposomes were
composed of phosphatidylcholines and varying contents of cholesterol and/or a
polyethylene glycol-modified phospholipid. We demonstrated that the efficiency of
penetration into spheroids increased with the bending modulus (i.e., membrane
rigidity) of the liposome, as determined by atomic force microscopy (correlation
coefficient, 0.84). To clarify the mechanism by which membrane rigidity
contributes to the penetration behavior of liposomes, we also analyzed the
cellular uptake using monolayer cells. We showed that penetration efficiency was
explained partially by cellular uptake efficiency, but that other factors such as
liposome diffusion efficiency in the intercellular space of tumor spheroids
contributed. Our results quantitatively demonstrate that the bending modulus of
the liposomal membrane is a major determinant of liposomal penetration into three
dimensional spheroids. The present study will contribute to the understanding and
control of tumor penetration of liposomal formulations.
PMID- 28410441
TI - Visualization of Electron Paramagnetic Resonance Hyperfine Structure Coupling
Pathways.
AB - The close relation between the EPR hyperfine coupling constant and NMR indirect
spin-spin coupling constant is well-known. For example, the Karplus-type
dependence of hyperfine constants on the dihedral angle, originally proposed for
NMR spin-spin coupling, is widely used in pNMR studies. In the present work we
propose a new tool for visualization of hyperfine coupling pathways based on our
experience with visualization of NMR indirect spin-spin couplings. The plotted 3D
function is the difference between the total electron densities when the magnetic
moment of the nucleus of interest changes its sign and as such is an observable
from the physical point of view. It has been shown that it is proportional to the
linear response of the spin density to the nuclear spin (i.e., magnetic moment).
In contrast to the widely used visualization of spin density, our new approach
depicts only the part of the electron cloud of a molecule that is affected by the
interaction of the unpaired electron(s) with the desired nuclear magnetic moment.
Because visualization of NMR spin-spin couplings and hyperfine interaction is
based on the same ideas and done using similar techniques, it allows a direct
comparison of the corresponding pathways for the two phenomena so as to analyze
their resemblance and/or dissimilarity.
PMID- 28410442
TI - Development of an Acrylate Derivative Targeting the NLRP3 Inflammasome for the
Treatment of Inflammatory Bowel Disease.
AB - Pharmacological inhibition of NLRP3 inflammasome activation may offer a new
option in the treatment of inflammatory bowel disease. In this work, we report
the design, synthesis, and biological screening of a series of acrylate
derivatives as NLRP3 inhibitors. The in vitro determination of reactivity,
cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the
selection of 11 (INF39), a nontoxic, irreversible NLRP3 inhibitor able to
decrease interleukin-1beta release from macrophages. Bioluminescence resonance
energy transfer experiments proved that this compound was able to directly
interfere with NLRP3 activation in cells. In vivo studies confirmed the ability
of the selected lead to alleviate the effects of colitis induced by 2,4
dinitrobenzenesulfonic acid in rats after oral administration.
PMID- 28410443
TI - Molecular Characterization of Volatiles and Petrochemical Base Oils by Photo
Ionization GC*GC-TOF-MS.
AB - The characterization of organic mixtures by comprehensive two-dimensional gas
chromatography (GC*GC) coupled to electron impact (EI) ionization time-of-flight
mass spectrometry (TOF-MS) allows the detection of thousands of compounds.
However, owing to the exhaustive fragmentation following EI ionization, despite
the use of mass spectral libraries, a majority of the compounds remains
unidentified because of the lack of parent ion preservation. Thus, soft
ionization energies leading to organic compounds being ionized with limited or no
fragmentation, retaining the molecular ion, has been of interest for many years.
In this study, photoionization (PI) was evaluated as the ion source for GC*GC-TOF
MS measurements. First, capabilities and limitations of PI were tested using an
authentic mixture of compounds of several chemical classes. Ionization energy
exhibited by PI, equivalent to 10.8 eV, resulted in significant retention of
molecular ion information; [M]+* for alkanes, ketones, FAMEs, aromatics, [M-H]+*
for chloroalkanes, and [M-H2O]+* for alcohols. Second, considering the potential
of PI for hydrocarbons, base oils, complex mixtures of saturated and unsaturated
hydrocarbons blended for finished lubricant formulations, were extensively
evaluated. Several chemical classes of hydrocarbons were positively identified
including a large number of isomeric compounds, both aliphatics and cyclics.
Interestingly, branched-alkanes were ionized with lower excess internal energy,
not only retaining the molecular ions but also exhibiting unique fragmentation
patterns. The results presented herein offer a unique perspective into the
detailed molecular characterization of base oils. Such unprecedented
identification power of PI coupled with GC*GC-TOF-MS is the first report covering
volatiles to low-volatile organic mixtures.
PMID- 28410444
TI - Verification of Nonequilibrium Mechanism of Ultrafast Charge Recombination in
Excited Donor-Acceptor Complexes.
AB - Control of charge transfer requires knowledge of its detailed mechanism. Due to
the large number of known mechanisms, the identification of the mechanism in
specific systems is a challenge so far. In this article we propose the idea of
how to distinguish between thermal and nonequilibrium modes of charge
recombination in excited donor-acceptor complexes. Simulations of the effect of
solvent relaxation time scale on ultrafast charge recombination kinetics in
photoexcited donor-acceptor complexes within the framework of the multichannel
stochastic model have shown that a series of regularities inherent to the thermal
and nonequilibrium charge transfer can strongly differ. Among them there are
opposite regularities, for example, the dependence of the dynamic solvent effect
on the free energy gap. In particular, theory predicts that in ultrafast charge
recombination of excited donor-acceptor complexes the dynamic solvent effect is
weak in the area of weak exergonicity and becomes stronger in the area of
stronger exergonicity whereas for the thermal reactions an opposite trend is
expected. Comparison of such trends with experimental data implemented in this
article allowed establishing the regime in which the reaction proceeds. It is
shown that observation of dynamic solvent effect in the region of strong
exergonicity for ultrafast charge recombination is decisive evidence in favor of
nonequilibrium mechanism.
PMID- 28410445
TI - Integrative Skin Care: Dermatology and Traditional and Complementary Medicine.
AB - Skin problems and diseases are extremely common globally and, due to their
visibility, often result in severe distress and stigma for sufferers. Traditional
(i.e., indigenous or local) and complementary health systems are widely used and
incorporate many treatment modalities suitable for skin care, and a body of
evidence for their efficacy and safety has built up over many decades. These
approaches are often used as part of a broader "integrative medicine" (IM)
approach that may also include, for example, nutrition and mind-body approaches.
This article presents an overview of current knowledge about traditional and
complementary medicine (T&CM) and IM principles and practices for skin health;
reviews published epidemiologic studies, clinical trials, and wider literature;
and discusses the challenges of conducting research into T&CM and IM. It also
highlights the need for an innovative research agenda-one which is congruent with
the principles of IM, as well as taking policy and public health dimensions into
consideration.
PMID- 28410446
TI - Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in
Patients with Bipolar Disorder.
AB - OBJECTIVES: This study focused on patients with bipolar disorder (BD), several
years after their participation in mindfulness-based cognitive therapy (MBCT). It
aimed at documenting sustained mindfulness practice, perceived long-term benefit
from the program, and changes regarded as direct consequences of the
intervention. DESIGN: This cross-sectional survey took place at least 2 years
after MBCT for 70.4% of participants. LOCATION: It was conducted in two
specialized outpatient units for BDs that are part of the Geneva University
Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). SUBJECTS:
Eligibility criteria were a diagnosis of BD according to DSM-IV and participation
in at least four MBCT sessions. Response rate was 66.4%. The final sample
included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). OUTCOME MEASURES: A
questionnaire retrospectively assessed patient-perceived change, benefit from
MBCT, and current mindfulness practice. RESULTS: Proportions of respondents who
practiced mindfulness at least once a week were 54.9% for formal practice (body
scan, sitting meditation, mindful walking, or movements) and 57.7% for informal
practice (mindful daily activities). Perceived benefit for the prevention of
relapse was moderate, but patients acknowledged long-lasting effects and
persistent changes in their way of life. Formal mindfulness practice at least
once a week tended to be associated with increased long-lasting effects (p =
0.052), whereas regular informal practice and mindful breathing were
significantly associated with persistent changes in daily life (p = 0.038) and
better prevention of depressive relapse (p = 0.035), respectively. The most
frequently reported positive change was increased awareness of being able to
improve one's health. CONCLUSIONS: Despite methodological limitations, this
survey allowed documenting mindfulness practice and perceived sustained benefit
from MBCT in patients with BD. Participants particularly valued increased
awareness that they can influence their own health. Both informal and formal
practices, when sustained in the long term, might promote long-lasting changes.
PMID- 28410447
TI - Correction to: Hum Gene Ther Clin Devel 2017;28(1):17-27.
PMID- 28410448
TI - IL17A Polymorphism Is Not Associated with Human T-Lymphotropic Virus 1-Associated
Myelopathy/Tropical Spastic Paraparesis.
AB - The human T-lymphotropic virus 1 (HTLV-1) is the causative agent of HTLV-1
associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study
investigated the association between the rs2275913 polymorphism in the IL17A gene
and the development of HAM/TSP. Peripheral blood samples were collected from 116
patients (29 symptomatic patients with HAM/TSP and 87 asymptomatic) with a
positive diagnosis of HTLV-1. The single nucleotide polymorphism genotyping was
carried out by real time PCR using TaqMan probes. In addition, serum levels of IL
2, IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, and IL-17 were measured in 64
infected individuals from the study (47 asymptomatic and 17 HAM/TSP), using
cytometric bead array technique. No significant differences were found in
genotypic and allelic frequencies between the groups. Analysis of cytokine levels
showed highest concentrations of IFN-gamma and TNF-alpha in HAM/TSP patients. The
results of the present study, therefore, suggest a lack of association between
the rs2275913 polymorphism in the IL17A gene and the presence of HAM/TSP.
PMID- 28410449
TI - The Suffering Pictogram: Measuring Suffering in Palliative Care.
AB - BACKGROUND: Measuring suffering objectively presents a challenge because
suffering is a unique and subjective experience. However, objective tools are of
profound importance in the detection and management of suffering in clinical
practice for optimal patient care. OBJECTIVE: The objective of the study is to
assess the psychometric properties of the Suffering Pictogram, a new suffering
assessment instrument on a population of palliative care patients. DESIGN AND
SETTING: This is a validation study conducted at University of Malaya Medical
Centre, Kuala Lumpur, Malaysia. Ninety one palliative care patients were
recruited. Patients were interviewed with the Suffering Pictogram and FACIT-Sp.
RESULTS: The median completion time for the Suffering Pictogram was five minutes.
The Suffering Pictogram showed good internal consistency, with a Cronbach's alpha
of 0.836. The total scores of the Suffering Pictogram correlated strongly and
negatively with FACIT-Sp total score (Spearman's Rho = -0.625, p < 0.001).
CONCLUSION: The Suffering Pictogram is a brief, reliable, and valid instrument to
measure suffering in palliative care. The instrument can be used as a screening
tool to detect suffering directly.
PMID- 28410450
TI - Delirium: Use Antipsychotics When Appropriate and Appropriately.
PMID- 28410451
TI - Advances in Innate Antiviral Immunity.
PMID- 28410452
TI - Notch Signaling Regulates Circulating T Helper 22 Cells in Patients with Chronic
Hepatitis C.
AB - Notch signaling enhanced the response of interleukin (IL)-22-producing CD4+ T
cells that were defined as T helper 22 (Th22) cells, and Notch-aryl hydrocarbon
receptor (AhR)-IL-22 axis fine-tuned inflammatory response. Previous studies have
demonstrated that both Notch signaling and Th22 cells took part in the
pathogenesis of chronic hepatitis C virus (HCV) infection. Thus, in this study,
we aimed at examining the regulatory role of Notch signaling in Th22 cells in HCV
infection. A total of 59 patients with chronic hepatitis C and 22 normal controls
(NCs) were enrolled in this study. The percentage of Th22 cells and mRNA
expression of related transcriptional factors and cytokines were analyzed in
response to gamma-secretase inhibitor. Th22 cell frequency was significantly
elevated in chronic hepatitis C in comparison with that in NCs. Inhibition of
Notch signaling downregulated HCV-specific Th22 cells and IL-22 production, which
was accompanied by the reduction of AhR and modulatory cytokines (IL-6 and tumor
necrosis factor-alpha). Moreover, the suppression of Notch signaling also
decreased the IL-22-mediated antimicrobial response in both normal and HCV
infected HepG2 cells/Huh7.5 cells. This process was also accompanied by the
depression of signal transducers and activators of transcription 3 signaling. In
conclusion, the current results suggested that Notch signaling acted as a
critical pathway in determining the response to IL-22 in chronic hepatitis C.
Thus, Notch-Th22 axis might be considered a new therapeutic target for HCV
infected patients.
PMID- 28410453
TI - Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.
AB - BACKGROUND: Multiple sclerosis is considered a complex and heterogeneous disease.
Approximately 85% of patients with multiple sclerosis indicate impaired gait as
one of the major limitations in their daily life. Acupuncture studies found a
reduction of spasticity and improvement of fatigue and imbalance in patients with
multiple sclerosis, but there is a lack of studies regarding gait. DESIGN: We
designed a study of acupuncture treatment, according to the Heidelberg model of
Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful
therapeutic strategy in patients with gait impairment in multiple sclerosis of
relapsing-remitting type. The sample consisted of 20 individuals with diagnosis
of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated
by the 25-foot walk test. RESULTS: The results showed differences in time to walk
25 feet following true acupuncture. In contrast, there was no difference in time
to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of
cases showed an improvement in 25-foot walk test, compared with 45% when sham
acupuncture was done. CONCLUSIONS: Our study protocol provides evidence that
acupuncture treatment can be an attractive option for patients with multiple
sclerosis, with gait impairment.
PMID- 28410454
TI - Transcriptomic Analysis of Host Immune Response in the Skin of Chickens Infected
with Marek's Disease Virus.
AB - Marek's disease virus (MDV), a highly cell-associated oncogenic alpha
herpesvirus, is the causative agent of T cell lymphoma and neuropathic disease
called Marek's disease. The skin is the only anatomical site where infectious
enveloped cell-free virions are produced and shed into the environment. Studies
have demonstrated that MDV infection induces immunological responses within the
skin, including the release of cytokines and the recruitment of T lymphocytes.
The host immune response, however, is not sufficient to block replication and
shedding of the virus particles from the skin. In this study, we examined the
gene expression profiling in the skin tissues of MDV-infected chickens to
identify viral-induced alterations in the host gene expression pattern. To
identify these genes in an unbiased and comprehensive manner, we performed RNA
seq on skin samples of MDV-infected chickens at 10, 20, and 30 days postinfection
(dpi). We identified 820, 1,333, and 1,571 upregulated genes in the skin of MDV
infected chickens at 10, 20, and 30 dpi, respectively. In addition, we identified
461, 878, and 1,751 downregulated genes corresponding to the same time points,
respectively. Analysis of the upregulated genes resulted in the identification of
multiple gene ontology (GO) categories, with most falling under the host immune
response. Searching these immune related GO categories, we identified six genes,
gga-let-7d, interleukin 22 receptor subunit alpha 2, tumor necrosis factor
receptor superfamily member 21, Proline-serine-threonine phosphatase-interacting
protein 2, Suppressor of cytokine signaling (SOCS)1, and SOCS3, with known
immunosuppressive properties that are upregulated in the skin of MDV-infected
chickens.
PMID- 28410455
TI - Diallyl Polysulfides from Allium sativum as Immunomodulators, Hepatoprotectors,
and Antimycobacterial Agents.
AB - Mycobacterium tuberculosis remains one of the world's deadliest killers, with an
annual death rate of ~1.5 million. The medicinal effects of garlic have been well
documented, and natural products have been shown to have antimycobacterial
activity. The current study evaluated the efficacy of six Allium sativum L.
polysulfide mixtures as antimycobacterial agents together with their cytotoxic,
immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue
assay was used to determine the minimum inhibitory concentrations (MIC).
Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC).
Excreted cytokine levels were determined by utilizing an enzyme-linked
immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations
of polysulfide mixtures. Human C3A liver cells were utilized in the
hepatoprotective study, to assess the protective effect against the toxicity
induced by acetaminophen. Samples with higher amounts of diallyl trisulfide
(Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of
2.5 MUg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity
in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest,
with a selectivity index close to one. Two samples, G3 and G6 containing higher
amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed
>50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin,
which showed a hepatoprotective effect of 30% at the tested concentration.
Diallyl tetrasulfide showed significant antimycobacterial activity. A combination
of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of
hepatoprotective activity.
PMID- 28410456
TI - Use of Bone Morphogenetic Protein 15 Polymorphisms to Predict Ovarian Stimulation
Outcomes in Infertile Brazilian Women.
AB - AIMS: Polymorphisms in the gene encoding bone morphogenetic protein 15 (BMP15)
can result in inhibited secretion or lowered bioactivity of the BMP15 protein.
BMP15 levels are associated with follicle-stimulating hormone receptor (FSHR)
action on granulosa cells, wherein FSHR increases the sensitivity of ovarian
follicles to follicle-stimulating hormone (FSH). In this study we evaluated the
BMP15 polymorphisms A905 > G/rs3897937, C901 > T/rs17003221, and C-9 >
G/rs3810682 in infertile Brazilian women in terms of anti-Mullerian hormone
(AMH), FSH, and estradiol serum levels, as well as controlled ovarian
hyperstimulation response and assisted reproduction outcomes. METHODS: A cross
sectional study comprising 186 infertile women who underwent the first cycle of
high complexity assisted reproduction treatment was conducted using the TaqMan
assay for quantitative polymerase chain reaction genotyping. Serum AMH, FSH, and
estradiol levels were measured by enzyme-linked immunosorbent assay. RESULTS: For
C901 > T (rs17003221) carriers, there was a statistically significant difference
among carriers of a polymorphic BMP15 genotype (TT) and the estradiol
concentration. These women had higher estradiol levels than women who had
homozygous wild type or heterozygous genotypes. There was also a positive
correlation between serum AMH and the C-9 > G (rs3810682) polymorphism, wherein
women carrying both polymorphic alleles (homozygous, GG) had higher average AMH
levels than heterozygous women. However, none of the three polymorphisms studied
showed a statistically significant correlation with assisted reproduction
outcome. DISCUSSION: Oocytes are known to secrete factors that regulate
follicular development and oocyte maturation. Abnormal expression of these
factors may thus be involved in follicular development disorders. A recent study
highlighted the importance of BMP15 in regulating ovulation rates in sheep and
that heterozygous deletions in the -9C > G polymorphism reduced BMP15
concentrations, increased granulosa cell FHSR mRNA levels, elevated estrogen
secretion, and activated production of stem cell factors. In this study we found
that BMP15 polymorphisms affected estrogen and AMH levels. CONCLUSION: BMP15
polymorphisms are not correlated with ovarian stimulation and assisted
reproduction outcomes in infertile Brazilian women.
PMID- 28410457
TI - Editorial Comment.
PMID- 28410458
TI - Editorial Comment.
PMID- 28410459
TI - Reply by Authors.
PMID- 28410460
TI - Anisotropic diffusion phantoms based on microcapillaries.
AB - Diffusion MRI is an efficient and widely used technique for the investigation of
tissue structure and organisation in vivo. Multiple phenomenological and
biophysical diffusion models are intensively exploited for the analysis of the
diffusion experiments. However, the verification of the applied diffusion models
remains challenging. In order to provide a "gold standard" and to assess the
accuracy of the derived parameters and the limitations of the diffusion models,
anisotropic diffusion phantoms with well known architecture are demanded. In the
present work we built four anisotropic diffusion phantoms consisting of hollow
microcapillaries with very small inner diameters of 5, 10 and 20MUm and outer
diameters of 90 and 150MUm. For testing the suitability of these phantoms, we
performed diffusion measurements on all of them and evaluated the resulting data
with a set of popular diffusion models, such as diffusion tensor and diffusion
kurtosis imaging, a two compartment model with intra- and extra-capillary water
spaces using bi-exponential fitting, and time-dependent diffusion coefficients in
Mitra's limit. The perspectives and limitations of these diffusion phantoms are
presented and discussed.
PMID- 28410461
TI - Gradients of fear: How perception influences fear generalization.
AB - The current experiment investigated whether overgeneralization of fear could be
due to an inability to perceptually discriminate the initial fear-evoking
stimulus from similar stimuli, as fear learning-induced perceptual impairments
have been reported but their influence on generalization gradients remain to be
elucidated. Three hundred and sixty-eight healthy volunteers participated in a
differential fear conditioning paradigm with circles of different sizes as
conditioned stimuli (CS), of which one was paired to an aversive IAPS picture.
During generalization, each subject was presented with one of 10 different sized
circles including the CSs, and were asked to categorize the stimulus as either a
CS or as novel after fear responses were recorded. Linear mixed models were used
to investigate differences in fear generalization gradients depending on the
participant's perception of the test stimulus. We found that the incorrect
perception of a novel stimulus as the initial fear-evoking stimulus strongly
boosted fear responses. The current findings demonstrate that a significant
number of novel stimuli used to assess generalization are incorrectly identified
as the initial fear-evoking stimulus, providing a perceptual account for the
observed overgeneralization in panic and anxiety disorders. Accordingly,
enhancing perceptual processing may be a promising treatment for targeting
excessive fear generalization.
PMID- 28410462
TI - Health service provision for people with epilepsy in sub-Saharan Africa: A
situational review.
AB - BACKGROUND: Epilepsy is a public health issue in sub-Saharan Africa (SSA) where
many people with the condition receive no treatment. Health-care services for
epilepsy in this region have not been comprehensively assessed. We examined key
features of epilepsy health services provided in SSA. METHODOLOGY: This was a
scoping review conducted using pre-specified protocols. We implemented an
electronic search strategy to identify relevant citations using PUBMED, EMBASE,
Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature
(CINAHL), African Index Medicus (AIM), Open Grey, Cochrane database, and Google
Scholar. Articles eligible for full-text review were screened and data of
interest were reported. RESULT: The search identified 81 eligible articles, forty
nine from East Africa, 19 from West Africa, 8 from South Africa, and 5 from
Central Africa. A variety of care services were identified, with reporting of
rural epilepsy care in 75% of retrieved articles mainly from East and South
African countries. The majority of the rural epilepsy clinics were health worker-
or nurse-led, reporting good seizure control in about two-thirds of patients
using phenobarbital as the most commonly prescribed antiepileptic drug. Funding
for rural epilepsy care came mainly from external donor agencies. CONCLUSION: We
attempted to provide a 'snapshot' of epilepsy care services in SSA. The successes
achieved in some of the centers are due to the use of existing primary health
care systems and employing non-physician health-care personnel. The true picture
of epilepsy care coverage is not apparent due to the lack of data and proper
health system structure in most parts of SSA. As more individuals begin to
receive care, the long-term funding for epilepsy care in African countries will
depend on the commitment of their respective governments.
PMID- 28410463
TI - VEGF treatment during status epilepticus attenuates long-term seizure-associated
alterations in astrocyte morphology.
AB - Vascular endothelial growth factor (VEGF) treatment during pilocarpine-induced
status epilepticus (SE) causes sustained preservation of behavioral function in
rats in the absence of enduring neuroprotection (Nicoletti et al., 2010),
suggesting the possibility that other cells or mechanisms could be involved in
the beneficial effects of VEGF during SE. Astrocytes have been reported to
contribute to epileptiform discharges in the hippocampus (Tian et al., 2005; Kang
et al., 1998) and to express VEGF receptors (Krum & Rosenstein, 2002). We report
here that VEGF treatment significantly alters multiple astrocyte parameters. This
study investigated astrocyte morphology one month after SE in animals treated
with VEGF or inactivated VEGF control protein during SE. Individual GFAP
immunostained astrocytes from CA1 and dentate gyrus hilus were traced and
morphologically quantified, and both somatic and process structures were
analyzed. VEGF treatment during SE significantly prevented post-SE increases in
number of branch intersections, process length, and node count. Furthermore,
analysis of distance to nearest neighboring astrocytes revealed that VEGF
treatment significantly increased inter-astrocyte distance. Overall, VEGF
treatment during SE did not significantly alter the shape of the astrocytes, but
did prevent SE-induced changes in branching complexity, size, and spatial
patterning. Because astrocyte morphology may be related to astrocyte function, it
is possible that VEGF's enduring effects on astrocyte morphology may impact the
functioning of the post-seizure hippocampus.
PMID- 28410464
TI - Surgical outcomes in two different age groups with Focal Cortical Dysplasia type
II: Any real difference?
AB - OBJECTIVE: Focal Cortical Dysplasias (FCDs) represent a common architectural
cortical disorder underlying drug-resistant focal epilepsy. So far, studies aimed
at evaluating whether age at surgery is a factor influencing surgical outcome are
lacking, so that data on the comparison between patients harboring Type II FCD
operated at younger age and those operated at adult age are still scarce. We
compared presurgical clinical features and surgical outcomes of patients with
histopathologically diagnosed Type II FCD undergoing surgery at an earlier age
with those operated after 20 years of age. METHODS: We retrospectively analyzed
1660 consecutive patients operated at the "Claudio Munari" Epilepsy Surgery
Centre. There were 289 patients (17.4%) with a neuropathological diagnosis of
Type II FCD. We included two different groups of patients, the first one
including patients operated on at less than 6years, the second sharing the same
seizure onset age but with delayed surgery, carried out after the age of 20.
Seizure characteristics and, neuropsychological and postoperative seizure
outcomes were evaluated by study group. RESULTS: Forty patients underwent surgery
before the age of 6 and 66 patients after the age of 20. Surgical outcome was
favorable in the whole population (72.6% were classified in Engel's Class Ia+Ic),
independently from age at surgery. In the children group, 32 patients were
classified in Class I, including 30 (75%) children in classes Ia and Ic. In the
adult group, 53 belonged to Class I of whom 47 (71%) were in classes Ia and Ic.
The percentage of permanent complications, the surgical outcomes, and AED
withdrawal did not significantly differ by study group. CONCLUSION: Our results
indicate that there is no difference between the groups, suggesting that outcome
depends mainly on the histological findings and not on timing of surgery.
PMID- 28410465
TI - Potentially preventable complications in epilepsy admissions: The "weekend
effect".
AB - INTRODUCTION: Epilepsy affects approximately 1% of the population in the United
States with frequent hospital admissions accounting for a significant burden on
patients and society as a whole. Weekend admissions have generally been found to
have poorer outcomes compared to weekday admissions with increased rates of
preventable complications, such as nationally identified "hospital-acquired
conditions" (HAC). OBJECTIVE: This study aimed to assess the impact of weekend
admission on HACs and mortality in the adult epilepsy population. PARTICIPANTS:
All adult patients with epilepsy hospitalized in the U.S. from 2000 to 2010 in
the Nationwide Inpatient Sample. RESULTS: There were 12,997,181 admissions for
epilepsy with 10,106,152 (78%) weekday, 2,891,019 (22%) weekend, and 10 (<0.1%)
missing admissions. Weekend admissions saw a 10% increased likelihood of both
HACs (RR=1.10, 95% CI:1.09, 1.11, p<0.01) and mortality (RR=1.10, 95% CI: 1.09,
1.11, p<0.01) compared to weekday admissions. The occurrence of HAC was
associated with higher inpatient charges (RR=1.36, 95% CI: 1.35, 1.36, p<0.01),
pLOS (RR=1.21, 95% CI: 1.21, 1.22, p<0.01), and higher mortality (RR=1.13, 95%
CI: 1.12, 1.14, p<0.01). CONCLUSION: Prior studies have shown weekend admissions
are usually associated with higher rates of complications leading to higher costs
and a longer hospital stay. Likewise, weekend admissions for epilepsy were
associated with increased rates of HACs and mortality; however, they were also
negatively associated with LOS and total charge. Thus, weekend admissions for
epilepsy should be considered high risk with greater effort made to mitigate
these risks.
PMID- 28410466
TI - History of surgery for temporal lobe epilepsy.
AB - The history of epilepsy and its treatment goes back to ancient times when it
included medicinal herbs, lifestyle modifications, and even surgery. Trepanation
is considered the oldest surgical procedure for the treatment of epilepsy. The
first series of temporal lobectomies for the treatment of drug-resistant epilepsy
were reported by Penfield and Flanigin (1950). During the years since then,
neuroimaging and other technologies have had remarkable and revolutionary
progress. This progress has resulted in tremendous advancements in understanding
the underlying causes and pathophysiology of epilepsies. With the help of these
technologies and advancements, we may now offer surgery as a safer therapeutic
option to more patients who are suffering from drug-resistant temporal lobe
epilepsy. However, the degree of improvement in surgery outcome has not been
proportionate to the technological progress.
PMID- 28410468
TI - Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp,
Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.
AB - The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim
(TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single
dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed.
In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg
(drug weight/body weight). In multiple-dose oral administration, shrimps were fed
three times a day for three consecutive days at a dose of 100mg/kg. The results
showed the kinetic characteristic of SMZ was different from TMP in Pacific white
shrimp. In the single-dose administration, the SMZ was widely distributed in the
tissues, while TMP was highly concentrated in the hepatopancreas. The t1/2z
values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In
the multiple-dose administration, SMZ accumulated well in the tissues, and
reached steady state level after successive administrations, while TMP did not.
TMP concentration even appeared the downward trend with the increase of drug
times. Compared with the single dose, the t1/2z values of SMZ in hepatopancreas
(8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the
haemolymph dropped (13.76-11.03) in the multiple-dose oral administration.
Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53
9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following
single-dose and multiple-dose oral administration in Pacific white shrimps. In
addition, it is worth mentioning that the ratios of SMZ and TMP were unusually
larger than the general aim ratio.
PMID- 28410467
TI - Examination of the interpersonal model of loss of control eating in the
laboratory.
AB - BACKGROUND: The interpersonal model of loss of control (LOC) eating proposes that
interpersonal problems lead to negative affect, which in turn contributes to the
onset and/or persistence of LOC eating. Despite preliminary support, there are no
data examining the construct validity of the interpersonal model of LOC eating
using temporally sensitive reports of social stress, distinct negative affective
states, and laboratory energy intake. METHOD: 117 healthy adolescent girls (BMI:
75th-97th %ile) were recruited for a prevention trial targeting excess weight
gain in adolescent girls who reported LOC eating. Prior to the intervention,
participants completed questionnaires of recent social stress and consumed lunch
from a multi-item laboratory test meal. Immediately before the test meal,
participants completed a questionnaire of five negative affective states (anger,
confusion, depression, fatigue, anxiety). Bootstrapping mediation models were
conducted to evaluate pre-meal negative affect states as explanatory mediators of
the association between recent social stress and palatable (desserts and snack
type) food intake. All analyses adjusted for age, race, pubertal stage, height,
fat mass percentage, and lean mass. RESULTS: Pre-meal state anxiety was a
significant mediator for recent social stress and palatable food intake (ps<.05).
By contrast, pre-meal state anger, confusion, depression, and fatigue did not
mediate the relationship between social stress and palatable food intake
(ps>.05). DISCUSSION: Pre-meal anxiety appears to be the salient mood state for
the interpersonal model among adolescent girls with LOC eating. Interventions
that focus on improving both social functioning and anxiety may prove most
effective at preventing and/or ameliorating disordered eating and obesity in
these adolescents.
PMID- 28410469
TI - 18beta-Glycyrrhetinic acid, the major bioactive component of Glycyrrhizae Radix,
attenuates airway inflammation by modulating Th2 cytokines, GATA-3, STAT6, and
Foxp3 transcription factors in an asthmatic mouse model.
AB - 18beta-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae
Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological
properties. Although 18Gly is associated with immunoregulatory functions of
allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic
inflammatory lung disease have not been examined. Moreover, there are no in vivo
studies on the anti-asthmatic effects of 18Gly in allergic asthma. We
investigated its effect and mechanism of action in airway inflammation in a
BALB/c mouse model of allergic asthma. Interestingly, 18Gly strongly suppressed
airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T
helper type 2 (Th2) cytokines (interleukin (IL)-5 and IL-13) in bronchoalveolar
lavage fluid (BALF). It also attenuated lung IL-5, IL-13, and IL-4 expression,
but it upregulated peroxisome proliferator-activated receptor gamma (PPARgamma)
mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by
suppressing Th2 cytokines (IL-5, IL-13) production through upregulation of
forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of
transcription (STAT6), GATA-binding protein 3 (GATA-3), and retinoic acid-related
orphan receptor gamma t (RORgammat) expression. These results suggest that the
anti-asthmatic activity of 18Gly may occur by the suppression of IL-5, IL-13, and
OVA-specific Immunoglobulin E (IgE) production through inhibition of the
RORgammat, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription
pathway. Also, 18Gly treatment was protective against the oxidative stress by
inducing significant decrease of reactive oxygen species (ROS) generation in MH-S
alveolar macrophage cells. Our results suggest that 18Gly can improve allergic
asthma and can be a novel therapeutic component for the treatment of allergic
asthma.
PMID- 28410470
TI - The action congruency effect on the feelings of agency.
AB - Previous studies suggest that the sense of agency (SoA), the feeling of control
about one's own actions and ensuing effects is also generated during action
selection processes. We investigate whether the conflict at the action selection
stage induced by a supraliminal stimulus, modulates an implicit measure of SoA,
namely intentional binding. Furthermore, we were interested to investigate the
influence of different types of stimulus-response compatibility on SoA. To this
aim we compared the influence of an automatic imitation task and a stroop-like
task on intentional binding. In both tasks participants performed congruent and
incongruent fingers movements (key release) in response to an external stimulus.
Their movements caused an effect and participants estimated the time between
their action and the ensuing effect. We found a reduced intentional binding
effect in incongruent compared to congruent conditions in both tasks. The results
are discussed within the theoretical framework of the fluency of action.
PMID- 28410471
TI - Toxicity of titanium dioxide nanoparticles to Chlorella vulgaris Beyerinck
(Beijerinck) 1890 (Trebouxiophyceae, Chlorophyta) under changing nitrogen
conditions.
AB - The broad application of titanium dioxide nanoparticles (n-TiO2) in many consumer
products has resulted in the release of substantial quantities into aquatic
systems. While n-TiO2 have been shown to induce some unexpected toxic effects on
aquatic organisms such as microalgae, the influence of changing nutrient
conditions on the toxicity of the metal has not been investigated. We evaluated
the toxicity of n-TiO2 to Chlorella vulgaris under varying nitrogen conditions.
Limited nitrogen (2.2MUM) decreased growth and biomass (dry weight and pigment
content), while lipid peroxidation (malondialdehyde content), glutathione S
transferase activity (GST) and peroxidase (POD) activity were increased.
Similarly, exposure to n-TiO2 under replete nitrogen condition resulted in a
general decrease in growth and biomass, while GST and POD activities were
significantly increased. The combination of limited nitrogen with n-TiO2 exposure
further decreased growth and biomass, and increased GST and POD activities of the
microalga. These results suggest that in addition to the individual effects of
each investigated condition, nitrogen limitation makes C. vulgaris more
susceptible to the effects of n-TiO2 with regard to some physiological
parameters. This implies that the exposure of C. vulgaris and possibly other
green algae to this nanoparticle under limited or low nitrogen conditions may
negatively affect their contribution to primary production in oligotrophic
aquatic ecosystems.
PMID- 28410472
TI - Histological alterations in gills of Macrobrachium amazonicum juveniles exposed
to ammonia and nitrite.
AB - Aquaculture has shown great growth in the last decades. Due to the restrictions
on water use, production systems are becoming increasingly more intensive,
raising concerns about the production water quality. Macrobrachium amazonicum is
among the freshwater prawn species with favorable characteristics for production
and possibility of intensification. Nitrogen compounds such as ammonia and
nitrite affect the health of aquatic organisms since they quickly reach toxic
concentrations. These compounds can also cause damage to the gill structure,
leading to hypoxia in tissues, affecting acid-base balance, osmoregulation (salt
absorption) and ammonia excretion, decreasing the immune capacity of the animal
and, in extreme cases, cause death. The aim of this study was to assess
histological changes in the gills of Macrobrachium amazonicum juveniles subjected
to different concentrations of total ammonia and nitrite. The prawns were
subjected to different concentrations of those compounds and their gills were
removed and preserved for histological analysis. The gills were assessed for
changes according to the Organ Index (Iorg) and, for each change, an importance
factor (w) was attributed according to the degree of reversibility and applied
according to the degree of extension or frequency of the damage. The damage to
the gills in the treatments with 100% mortality, both for ammonia and nitrite,
corresponded to the high occurrence of progressive, regressive, circulatory, and
inflammation damages. The other treatments (which caused less mortality) had
mainly inflammation and regressive damages, whose occurrence increased according
to the increase in ammonia and nitrite concentration. The histological analysis
confirmed that the higher the total ammonia and nitrite concentrations, the
larger the damages caused to the gill structure and that lower nitrite
concentrations caused similar damages to those caused by higher total ammonia
concentrations, which reflects the lower capacity M. amazonicum has to tolerate
nitrite.
PMID- 28410474
TI - A methodology to determine natural radioactivity by gamma spectrometry without
using calibrated standard samples.
AB - When determining the radioactivity in materials by gamma spectra, different
processes are involved difficulting the fit. Besides, calibrated standard samples
are necessary. In this work we propose a methodology to determine natural
radioactivity using simulated gamma spectra by Monte Carlo and without the use of
calibrated standard samples. We applied this methodology to determine
radioactivity of K 40 isotopes from a light salt sample. Then we applied this
process in soil samples and the results where compared with the values obtained
by an other laboratory. In this comparison our results are on average a 13%
smaller.
PMID- 28410473
TI - Thyroid hormone parameters during pregnancy in relation to urinary bisphenol A
concentrations: A repeated measures study.
AB - BACKGROUND: Maternal supply of thyroid hormones during pregnancy serves a
critical role in fetal development. Although animal and in vitro studies provide
evidence for thyroid hormone disruption as a result of bisphenol A (BPA)
exposure, there is still a lack of evidence in human studies, particularly in the
context of pregnancy. OBJECTIVES: We aimed to explore the associations between
urinary BPA concentrations and plasma thyroid hormone parameters during gestation
in pregnant women, and also investigated potential windows of vulnerability
during gestation. METHODS: Our study population included 116 cases of preterm
birth and 323 controls from a nested case-control study. We measured BPA in urine
and thyroid hormone parameters in plasma samples collected at up to four study
visits during pregnancy (median for each visit: 9.64, 17.9, 26.0, and 35.1weeks
gestation). We used linear mixed models for repeated measures analyses, and
multivariate linear regression models stratified by study visit to explore
potential windows of susceptibility. RESULTS: In our repeated measures analysis,
BPA and thyrotropin (TSH) were inversely associated. An interquartile range (IQR)
increase in BPA was associated with an 8.21% decrease in TSH (95% confidence
interval [CI]: -14.2, -1.83), and a 4.79% increase in free T4 (95% CI: 0.82,
8.92). BPA and TSH were also inversely associated in our cross-sectional analyses
at visits 3 and 4. CONCLUSIONS: Our results suggest that TSH is inversely
associated with urinary BPA in a consistent manner across pregnancy. Disruption
of TSH levels during pregnancy can potentially impact child development and
interfere with normal birth outcomes.
PMID- 28410475
TI - Exploring the potential of Saccharomyces cerevisiae for biopharmaceutical protein
production.
AB - Production of recombinant proteins by yeast plays a vital role in the
biopharmaceutical industry. It is therefore desirable to develop yeast platform
strains for over-production of various biopharmaceutical proteins, but this
requires fundamental knowledge of the cellular machinery, especially the protein
secretory pathway. Integrated analyses of multi-omics datasets can provide
comprehensive understanding of cellular function, and can enable systems biology
driven and mathematical model-guided strain engineering. Rational engineering and
introduction of trackable genetic modifications using synthetic biology tools,
coupled with high-throughput screening are, however, also efficient approaches to
relieve bottlenecks hindering high-level protein production. Here we review
advances in systems biology and metabolic engineering of yeast for improving
recombinant protein production.
PMID- 28410476
TI - Fear reactivity to cognitive dyscontrol via novel head-mounted display perceptual
illusion exercises.
AB - BACKGROUND: Anxiety sensitivity cognitive concerns (ASCC), refer to fears of
mental catastrophe or losing control over mental processes. Recent findings show
that ASCC are related to suicide risk, mood disorders and trauma-related
disorders. Using controlled experimental psychopathology paradigms could be one
heretofore unutilized method of increasing understanding of ASCC. Our goal was to
test fear reactivity to four head-mounted display perceptual illusion challenges
designed to bring on feelings of cognitive dyscontrol (i.e., derealization,
depersonalization) in a group of high and low anxiety sensitivity cognitive
concerns participants. METHODS: Participants (N=49) with Anxiety Sensitivity
Index-3 cognitive scores at least 1.5 SD above or below the mean completed four
cognitive dyscontrol challenges utilizing head-mounted display technology.
RESULTS: Results showed all four challenges successfully elicited high cognitive
anxiety symptoms. Consistent with other laboratory challenge studies; high versus
low ASCC participants reported comparable cognitive symptoms but reported
significantly greater fear. LIMITATIONS: This was an initial proof of concept
study designed to examine fear reactivity to cognitive dyscontrol challenges.
Therefore, no control exercises were evaluated. CONCLUSIONS: The finding that
fear reactivity to the laboratory challenges can potentially serve as a viable
behavioral correlate of ASCC provides a potentially useful exposure exercise for
clients experiencing high levels of ASCC. Given the association between ASCC and
severe psychopathology, with further investigation and refinement, such exposure
exercises could be integrated into cognitive-behavioral treatments.
PMID- 28410477
TI - Anxiety among adults with a history of childhood adversity: Psychological
resilience moderates the indirect effect of emotion dysregulation.
AB - BACKGROUND: Adverse childhood experiences (ACEs) have been widely identified as
risk factors for increased symptoms of anxiety across the lifespan. Little is
known, however, about the processes by which ACEs set the stage for increased
symptoms of anxiety in adulthood. The current study evaluated whether emotion
dysregulation and psychological resilience influence the association between ACEs
and symptoms of anxiety. METHODS: A sample of adult primary care patients
(N=4006) completed self-report measures related to ACEs, symptoms of anxiety,
emotion dysregulation, and psychological resilience. RESULTS: A moderated
mediation analysis showed that emotion dysregulation mediated the association
between ACEs and anxiety symptoms, and that the strength of this effect varied as
a function of psychological resilience. Specifically, the influence of ACEs on
emotional dysregulation was stronger among individuals with low levels of
psychological resilience than among those with high levels of psychological
resilience. These findings remained significant when controlling for a range of
sociodemographic variables in the model. LIMITATIONS: Cross-sectional designs
preclude inferences about causality and self-report data may be susceptible to
reporting biases. Other psychological variables that may be relevant to the
current results, such as protective factors in childhood, were not assessed.
CONCLUSIONS: These results have implications for the conceptualization of ACEs,
emotion dysregulation, and psychological resilience in etiological models of
anxiety. They also highlight the relevance of ACEs, emotion dysregulation, and
psychological resilience to the detection, treatment, and prevention of anxiety
disorders.
PMID- 28410478
TI - Non-contrast MRI diagnosis of adhesive capsulitis of the shoulder.
AB - PURPOSE: To investigate non-contrast MRI findings of clinical adhesive
capsulitis. METHODS: 31 non-contrast, non-arthrographic, shoulder MRIs were
evaluated for coracohumeral ligament thickness, rotator interval infiltration,
and axillary recess thickening/edema. RESULTS: In detection of adhesive
capsulitis, sensitivity is 76.7% and specificity is 53.3% for coracohumeral
ligament thickening, sensitivity is 66.7% and specificity is 55.2% for
coracohumeral ligament thickening and rotator interval infiltration, and
sensitivity is 23.3% and specificity is 86.7% for coracohumeral ligament
thickening, rotator interval infiltration, and axillary recess thickening/edema.
CONCLUSIONS: Adhesive capsulitis can be accurately diagnosed on non-contrast MRI
shoulder examinations with appropriate clinical criteria without direct MR
arthrography.
PMID- 28410480
TI - Chemiluminescence noncompetitive immunoassay based on microchip electrophoresis
for the determination of beta-subunit of human chorionic gonadotropin.
AB - In this work, a microchip-electrophoresis chemiluminescence (MCE-CL)-based
immunoassay method was established for the determination of beta-subunit of human
chorionic gonadotropin (beta-HCG). This approach uses MCE-CL assay as a platform.
First, the beta-HCG antigen (Ag) binds to excess horseradish peroxidase (HRP)
labeled anti-beta-HCG antibodies (Ab*) to form an immune complex (Ag-Ab*).
Subsequently, the obtained Ag-Ab* complex and unreacted Ab* were separated by
MCE, and detected by CL. The CL intensity (peak high) of Ag-Ab* was used to
estimate beta-HCG concentration. The calibration curve between the peak high and
beta-HCG concentration showed a good linearity in the range of 0.6-60mIU/mL.
Based on a signal/noise ratio (S/N) of 3, the detection limit for beta-HCG was
estimated to be 0.36mIU/mL. The present method was successfully applied for the
detection of beta-HCG in human serum, and the serum content of beta-HCG from
three healthy subjects was found be in the range of 9.5-15.7mIU/mL, while that
from three ovarian cancer patients was found be in the range of 160.9
210.4mIU/mL. These results suggest that cancer patients have higher contents of
beta-HCG than healthy individuals do, indicating that this method can be applied
for assisting diagnosis of ovarian cancer in clinical application.
PMID- 28410479
TI - Analysis of sulfonamides, tilmicosin and avermectins residues in typical animal
matrices with multi-plug filtration cleanup by liquid chromatography-tandem mass
spectrometry detection.
AB - The frequent use of various veterinary drugs could lead to residue
bioaccumulation in animal tissues, which could cause dietary risks to human
health. In order to quickly analyze the residues, a liquid chromatography tandem
mass spectrometry (LC-MS/MS) method was developed for detecting Sulfonamides,
Tilmicosin and Avermectins (AVMs) residues in animal samples. For sample
preparation, modified QuEChERS (quick, easy, cheap, effective, rugged and safe)
and ultrasound-assisted extraction (UAE) methods were used. For sample cleanup, n
Hexane delipidation and multi-plug filtration cleanup (m-PFC) method based on
primary-secondary amine (PSA) and octadecyl-silica (C18) were used, followed by
LC-MS/MS analysis. It was validated on 7 animal matrices (bovine, caprine, swine
meat and their kidneys, milk) at two fortified concentration levels of 5 and
100MUg/kg. The recoveries ranged from 82 to 107% for all analytes with relative
standard deviations (RSDs) less than 15%. Matrix-matched calibrations were
performed with coefficients of determination above 0.998 for all analytes within
concentration levels of 5-500MUg/kg. The developed method was successfully used
to analysis veterinary drugs of real animal samples from local markets.
PMID- 28410481
TI - Leg symptoms associated with sacroiliac joint disorder and related pain.
AB - OBJECTIVE: The symptoms of sacroiliac joint (SIJ) disorders are usually detected
in the buttock and groin, and occasionally referred to the thigh and leg.
However, lumbar disorders also cause symptoms in these same body regions. The
presence of a characteristic, symptomatic pattern in the legs would be useful for
diagnosing SIJ disorders. This study aimed to identify specific leg symptoms in
patients with SIJ pain originating from the posterior sacroiliac ligament and
determine the rate of occurrence of these symptoms. PATIENTS AND METHODS: The
source population consisted of 365 consecutive patients from February 2005 to
December 2007. One hundred patients were diagnosed with SIJ pain by a
periarticular SIJ injection (42 males and 58 females, average age 46 years, age
range, 18-75 years). A leg symptom map was made by subtracting the symptoms after
a periarticular SIJ injection from the initial symptoms, and evaluating the rate
of each individual symptom by area. RESULTS: Ninety-four patients reported pain
at or around the posterior-superior iliac spine (PSIS). Leg symptoms comprised
pain and a numbness/tingling sensation; >=60% of the patients had these symptoms.
Pain was mainly detected in the back, buttock, groin, and thigh areas, while
numbness/tingling was mainly detected in the lateral to posterior thigh and back
of the calf. CONCLUSIONS: Leg symptoms associated with SIJ pain originating from
the posterior sacroiliac ligament include both pain and numbness, which do not
usually correspond to the dermatome. These leg symptoms in addition to pain
around the PSIS may indicate SIJ disorders.
PMID- 28410482
TI - Cheiro-pedal syndrome: A revisit of etiology, localization and outcome.
AB - OBJECTIVE: Cheiro-pedal syndrome (CPS) is an incomplete sensory disorder confined
to hand and foot and is generally considered a benign entity. However, knowledge
comes from case report or case series only. The aim of this study is to clarify
the etiology, localization and outcome of CPS. PATIENT AND METHOD: A total of 21
CPS patients from our database and another 9 patients from literature were
reviewed. CPS was classified into 4 types, namely unilateral and ipsilateral
(Type I), bilateral (Type II), incomplete bilateral (Type III), and crossed (Type
IV). RESULTS: They were 20 men and 10 women; including 20 Type I patients, 9 Type
II patients, 1 Type III patients, and 0 Type IV patient. Vascular disorders, non
vascular cervical disorder and polyneuropathy were the responsible causes in 18
patients, 7 patients, and 2 patients, respectively. Etiology was unknown in
another 3 patients. Lesions were located at brain parenchyma in 16 patients, and
cervical cord above C5 level in 9 patients. Disable motoroparesis occurred
between 4days to 2 months in two-third of deteriorated patients. In three
patients, their lesions were detected only on recurrence or exacerbation of CPS 4
months to 2 years later. Recovery, residual deficit and deterioration ensued in
44%, 28% and 28% patients, respectively. A 33.3% of brain involvement patients
and 100.0% of spinal involvement patients terminated to residual deficit or
deterioration. The sensitivity and specificity of prediction for deterioration
was 77.8% and 100%, respectively, by type II or III CPS. CONCLUSION: CPS is
actually not a benign neurological disorder but a sensory alarm sign. A thorough
examination of brain parenchyma and cervical spinal cord is urgent for
identifying any treatable or preventable pathological lesions to reduce harmful
consequence, especially in case of type II or III CPS.
PMID- 28410484
TI - Microalgae screening under CO2 stress: Growth and micro-nutrients removal
efficiency.
AB - Algae are one of the promising agents for greenhouse gas reduction and biofuel
production. Different technologies have been developed and introduced in last
decades for algae growth. Algae plays a very imperative role in the aquatic
ecosystem regarding CO2 reduction and micro-nutrient removal. In present
investigation, eight locally isolated (microalgae) strains and two pure strains
were studied. The selected microalgae were grown under variable CO2 concentration
and CO2 biofixation efficiencies along with micro-nutrient removal were
monitored. Among selected strains, three strains (UMN266, UMN268 and UTEX 2714
showed adaptability up to 20% CO2 concentration with high biomass production of
1.3, 1.4 and 1.21g/L, respectively, whereas UTEX 78 and UMN 230 growth was slow
under high CO2 concentration (20% CO2). However, in step wise CO2 feeding, the
growth of UTEX 78 and UMN 230 improved considerably and up to 0.9 and 0.97 (g/L)
biomasses were recorded, respectively. All algae strains showed high growth rate
at 2% CO2 feeding and nitrogen, phosphorus and ammonia removal from the simulated
media were also significant. The fast-growing microalgae species tolerant up to
20% CO2 concentration and could be used for flue gas mitigation and valuable
products production. These results can contribute to understand the nature of CO2
bio-fixation and microalgae could be a potential alternative for CO2 fixation.
PMID- 28410483
TI - Contributions of CD8 T cells to the pathogenesis of mouse adenovirus type 1
respiratory infection.
AB - CD8 T cells are key components of the immune response to viruses, but their roles
in the pathogenesis of adenovirus respiratory infection have not been
characterized. We used mouse adenovirus type 1 (MAV-1) to define CD8 T cell
contributions to the pathogenesis of adenovirus respiratory infection. CD8 T cell
deficiency in beta2m-/- mice had no effect on peak viral replication in lungs,
but clearance of virus was delayed in beta2m-/- mice. Virus-induced weight loss
and increases in bronchoalveolar lavage fluid total protein, IFN-gamma, TNF
alpha, IL-10, CCL2, and CCL5 concentrations were less in beta2m-/- mice than in
controls. CD8 T cell depletion had similar effects on virus clearance, weight
loss, and inflammation. Deficiency of IFN-gamma or perforin had no effect on
viral replication or inflammation, but perforin-deficient mice were partially
protected from weight loss. CD8 T cells promote MAV-1-induced pulmonary
inflammation via a mechanism that is independent of direct antiviral effects.
PMID- 28410485
TI - Impact of posttraumatic stress symptom dimensions on psychophysiological
reactivity to threat and reward.
AB - Posttraumatic stress symptoms (PTSS) are associated with significant distress and
impairment. Research has therefore focused on identifying neurobehavioral
deficits that contribute to the pathophysiology of PTSS. One issue that has
contributed to difficulty in identifying these deficits is the highly
heterogeneous nature of PTSS. PTSS is comprised of four, factor analytically
distinct dimensions of symptoms - re-experiencing, avoidance, hyperarousal, and
negative cognitions and mood. It is therefore unlikely that there is one single
mechanism that accounts for all of PTSS and elucidating neurobehavioral deficits
associated with specific PTSS symptom dimensions may better inform clinical
prevention and intervention efforts. Within the broader internalizing disorder
literature, two key constructs that contribute to psychopathology are aberrant
neural reactivity to threat and reward. However, the literature linking PTSS to
these deficits is mixed, suggesting that aberrant neural reactivity to threat or
reward may be specific to certain PTSS dimensions. In a sample of 51 trauma
exposed adults with a range PTSS, the present study therefore examined how the
four dimensions of PTSS uniquely relate to two well-validated event-related
potential (ERP) neural indices of threat and reward reactivity - the error
related negativity (ERN) and reward-related positivity (RewP), respectively.
Results indicated that hyperarousal symptoms were associated with enhanced ERN,
and enhanced RewP. In contrast, negative cognitions and mood symptoms were
uniquely associated with a more blunted RewP. These results indicate that certain
PTSS symptom dimensions have unique relations with neural indicators of threat
and reward reactivity and may therefore have distinct pathophysiologies.
PMID- 28410486
TI - How to treat Ebola virus infections? A lesson from the field.
AB - The reported case fatality ratios (CFR) of Ebola virus disease (EVD) have been as
high as 90% in previous outbreaks. While the cumulative CFR among patients
medically evacuated and treated in Western countries was inferior to 20%, it
peaked to approximately 75% between September and December 2014 in West Africa,
thereafter decreasing to less than 40% (May 2015) without current evidence of
major virus mutations capable to alter virus pathogenicity over the course of the
epidemic. Therefore, the observed diminution of CFR is likely to reflect
improvement of EVD patient care. Here, we summarize major lessons learned, that
is, progresses and knowledge gaps, about the clinical management of patients in
West African settings during the 2014-2016 outbreak.
PMID- 28410487
TI - Structural brain changes in medically refractory focal epilepsy resemble
premature brain aging.
AB - OBJECTIVE: We used whole brain T1-weighted MRI to estimate the age of individuals
with medically refractory focal epilepsy, and compared with individuals with
newly diagnosed focal epilepsy and healthy controls. The difference between
neuroanatomical age and chronological age was compared between the three groups.
METHODS: Neuroanatomical age was estimated using a machine learning-based method
that was trained using structural MRI scans from a large independent healthy
control sample (N=2001). The prediction model was then used to estimate age from
MRI scans obtained from newly diagnosed focal epilepsy patients (N=42), medically
refractory focal epilepsy patients (N=94) and healthy controls (N=74). RESULTS:
Individuals with medically refractory epilepsy had a difference between predicted
brain age and chronological age that was on average 4.5 years older than healthy
controls (p=4.6*10-5). No significant differences were observed in newly
diagnosed focal epilepsy. Earlier age of onset was associated with an increased
brain age difference in the medically refractory group (p=0.034). SIGNIFICANCE:
Medically refractory focal epilepsy is associated with structural brain changes
that resemble premature brain aging.
PMID- 28410488
TI - Understanding the potency of fatty acids with the amino acid side chains of
bovine beta lactoglobulin-A quantum chemical approach.
AB - The present study aims to spotlight on the strength of interaction between
different fatty acids with the Bovine-lactoglobulin (LGB) protein side chains
along with the crystal water molecules at M062X/def2-QZVP level of theory. To
analyse the role of carboxylic acid and its interaction with side chains and to
reveal the significance of carboxylic acid, it was replaced by Acyl chloride
(COCl), Acyl Bromide (COBr) and Acyl-Fluorine (COF) group and COS group. The
ligands are linear with a straight and branched chain of carbon atoms, but
extended methyl group make the ligand bend resulting in non-planar geometry. The
least and highest band gap energy reveals the conductivity properties of ligands.
3UEW, the Palmitic acid is well-built owing to the interaction with the amino
acid side chains Lys 69 and Glu 62 resulting in interaction energy of
124.98kcal/mol. 3D-NCIplot isosurface map and 2D-NCIplot graph plays a key role
to confirm and analyse the occurrence of various non covalent interactions. The
overall analysis of the fatty acids implies the fact that depending on the
aliphatic chain length, the carboxyl group was capable of positioning favourable
binding site.
PMID- 28410489
TI - The contribution of urbanization to non-communicable diseases: Evidence from 173
countries from 1980 to 2008.
AB - It is widely believed that the expanding burden of non-communicable diseases
(NCDs) is in no small part the result of major macro-level determinants. We use a
large amount of new data, to explore in particular the role played by
urbanization - the process of the population shifting from rural to urban areas
within countries - in affecting four important drivers of NCDs world-wide:
diabetes prevalence, as well as average body mass index (BMI), total cholesterol
level and systolic blood pressure. Urbanization is seen by many as a double-edged
sword: while its beneficial economic effects are widely acknowledged, it is
commonly alleged to produce adverse side effects for NCD-related health outcomes.
In this paper we submit this hypothesis to extensive empirical scrutiny, covering
a global set of countries from 1980-2008, and applying a range of estimation
procedures. Our results indicate that urbanization appears to have contributed to
an increase in average BMI and cholesterol levels: the implied difference in
average total cholesterol between the most and the least urbanized countries is
0.40mmol/L, while people living in the least urbanized countries are also
expected to have an up to 2.3kg/m2 lower BMI than in the most urbanized ones.
Moreover, the least urbanized countries are expected to have an up to 3.2p.p.
lower prevalence of diabetes among women. This association is also much stronger
in the low and middle-income countries, and is likely to be mediated by energy
intake-related variables, such as calorie and fat supply per capita.
PMID- 28410491
TI - Multi-ion detection and molecular switching behaviour of reversible dual
fluorescent sensor.
AB - The selective chemosensing behaviour of imidazole bisthiocarbohydrazone (IBTC)
towards F- and Cu2+ are studied via colorimetric, UV-Visible, fluorescence
spectra studies, and binding constants were calculated. The 1H NMR titration
study strongly support that the deprotonation of IBTC followed by the hydrogen
bond formation via N1H1 and N2H2 protons with fluoride ion. The fluorescence
inactive IBTC-Cu complex became fluorescence active in the presence of
perchlorate (ClO4-) ion. The selective detection of perchlorate ion was also
explained. The F- sensing mechanism of IBTC has been investigated by Density
Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT)
methods. The theoretical outcomes well reproduce the experimental results. And it
concluded the NH protons, nearby the imine group was first captured by the added
F- ion and then deprotonation happened followed by the formation of hydrogen
bond. The IBTC found good reversibility character with the alternative addition
of Ca2+ and F-. The multi-ion detection of IBTC was used to construct the NOR, OR
and INHIBITION molecular logic gates.
PMID- 28410492
TI - Synthesis and biological evaluation of novel indole-pyrimidine hybrids bearing
morpholine and thiomorpholine moieties.
AB - Based on our previous screening hit compound 1, a series of novel indole
pyrimidine hybrids possessing morpholine or thiomorpholine moiety were
synthesized via an efficient one-pot multistep synthetic method. The
antiproliferative activities of the synthesized compounds were evaluated in vitro
against four cancer cell lines including HeLa, MDA-MB-231, MCF-7, and HCT116. The
results revealed that most compounds possessed moderate to excellent potency. The
IC50 values of the most promising compound 15 are 0.29, 4.04, and 9.48 MUM
against MCF-7, HeLa, and HCT116 cell lines, respectively, which are 48.0, 4.9,
and 1.8 folds more active than the lead compound 1. Moreover, fluorescence
activated cell sorting analysis revealed that compound 14 showing the highest
activity against HeLa (IC50 = 2.51 MUM) displayed a significant effect on G2/M
cell-cycle arrest in a concentration-dependent manner in HeLa cell line. In
addition, representative nine active hybrids were evaluated for tubulin
polymerization inhibitory activities, and compound 15 exhibited the most potent
anti-tubulin activity showing 42% inhibition at 10 MUM. These preliminary results
encourage a further investigation on indole-pyrimidine hybrids for the
development of potent anticancer agents that inhibit tubulin polymerization.
PMID- 28410493
TI - Oxadiazole-substituted naphtho[2,3-b]thiophene-4,9-diones as potent inhibitors of
keratinocyte hyperproliferation. Structure-activity relationships of the
tricyclic quinone skeleton and the oxadiazole substituent.
AB - Novel analogues of oxadiazole-substituted naphtho[2,3-b]thiophene-4,9-diones were
synthesized in which the tricyclic quinone skeleton was systematically replaced
with simpler moieties, such as structures with fewer rings and open-chain forms,
while the oxadiazole ring was maintained. In addition, variants of the original
1,2,4-oxadiazole ring were explored. Overall, the complete three-ring quinone was
essential for potent suppression of human keratinocyte hyperproliferation,
whereas analogous anthraquinones were inactive. Also, the oxadiazole ring per se
was not sufficient to elicit activity. However, rearrangement of the heteroatom
positions in the oxadiazole ring resulted in highly potent inhibitors with
compound 24b being the most potent analogue of this series showing an IC50 in the
nanomolar range. Furthermore, experiments in isolated enzymatic assays as well as
in the keratinocyte-based hyperproliferation assay did not support a major role
of redox cycling in the mode of action of the compounds.
PMID- 28410494
TI - Enhancing the antimony sorption properties of nano titania-chitosan beads using
epichlorohydrin as the crosslinker.
AB - Antimony is classified as a pollutant of priority importance by USEPA. We have
earlier reported the synthesis of nano-titania impregnated epichlorohydrin
crosslinked chitosan (TA-Cts-Epi) beads, in a format suitable for large scale
applications with high sorption capacity for antimony. To understand the sorption
mechanism, and to fine tune the bead composition, the effect of crosslinking
density on the swelling and sorption properties of the beads was investigated in
detail. Epichlorohydrin effected significant changes in physical and sorption
properties of the beads. The antimony sorption capacity of the TA-Cts-Epi beads
prepared by crosslinking 0.3g non-crosslinked titania-chitosan beads (TA-Cts-NCL)
with 6.4mmol epichlorohydrin was 493MUmol/g, while those crosslinked with
0.64mmol showed a capacity of 133MUmol/g. Whereas, TA-Cts-NCL beads showed a
capacity of 75MUmol/g. The increase in uptake capacity with increase in
crosslinking demonstrated the active involvement of the epichlorohydrin moieties
in antimony binding leading to enhanced sorption. Apart from altering the
stability, swelling behaviour and sorption kinetics of the beads, crosslinking
significantly increased the uptake of the anionic species via electrostatic
interactions. Epichlorohydrin crosslinked chitosan beads prepared without TiO2
also showed similar behaviour. The results demonstrated the involvement of
chitosan, TiO2 and epichlorohydrin in sorption.
PMID- 28410490
TI - Survival of 86,690 patients with thyroid cancer: A population-based study in 29
European countries from EUROCARE-5.
AB - BACKGROUND: Incidence rates of thyroid cancer (TC) increased in several countries
during the last 30 years, while mortality rates remained unchanged, raising
important questions for treatment and follow-up of TC patients. This study
updates population-based estimates of relative survival (RS) after TC diagnosis
in Europe by sex, country, age, period and histology. METHODS: Data from 87
cancer registries in 29 countries were extracted from the EUROCARE-5 dataset. One
and 5-year RS were estimated using the cohort approach for 86,690 adult TC
patients diagnosed in 2000-2007 and followed-up to 12/31/2008. RS trends in 1999
2007 and 10-year RS in 2005-2007 were estimated using the period approach.
RESULTS: In Europe 2000-2007, 5-year RS after TC was 88% in women and 81% in men.
Survival rates varied by country and were strongly correlated (Pearson rho = 75%)
with country-specific incidence rates. Five-year RS decreased with age (in women
from >95% at age 15-54 to 57% at age 75+), from 98% in women and 94% in men with
papillary TC to 14% in women and 12% in men with anaplastic TC. Proportion of
papillary TC varied by country and increased over time, while survival rates were
similar across areas and periods. In 1999-2007, 5-year RS increased by five
percentage points for all TCs but only by two for papillary and by four for
follicular TC. Ten-year RS in 2005-2007 was 89% in women and 79% in men.
CONCLUSIONS: The reported increasing TC survival trend and differences by area
are mainly explained by the varying histological case-mix of cases.
PMID- 28410495
TI - Local induction of lymphangiogenesis with engineered fibrin-binding VEGF-C
promotes wound healing by increasing immune cell trafficking and matrix
remodeling.
AB - Lymphangiogenesis occurs in inflammation and wound healing, yet its functional
roles in these processes are not fully understood. Consequently, clinically
relevant strategies for therapeutic lymphangiogenesis remain underdeveloped,
particularly using growth factors. To achieve controlled, local capillary
lymphangiogenesis with protein engineering and determine its effects on fluid
clearance, leukocyte trafficking, and wound healing, we developed a fibrin
binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is
slowly released upon demand from infiltrating cells. Using a novel wound healing
model, we show that implanted fibrin containing FB-VEGF-C, but not free VEGF-C,
could stimulate local lymphangiogenesis in a dose-dependent manner. Importantly,
the effects of FB-VEGF-C were restricted to lymphatic capillaries, with no
apparent changes to blood vessels and downstream collecting vessels. Leukocyte
intravasation and trafficking to lymph nodes were increased in hyperplastic
lymphatics, while fluid clearance was maintained at physiological levels. In
diabetic wounds, FB-VEGF-C-induced lymphangiogenesis increased extracellular
matrix deposition and granulation tissue thickening, indicators of improved wound
healing. Together, these results indicate that FB-VEGF-C is a promising strategy
for inducing lymphangiogenesis locally, and that such lymphangiogenesis can
promote wound healing by enhancing leukocyte trafficking without affecting
downstream lymphatic collecting vessels.
PMID- 28410496
TI - Acute kidney injury in symptomatic primary Epstein-Barr virus infectious
mononucleosis: Systematic review.
AB - BACKGROUND AND OBJECTIVES: Textbooks and reviews do not mention the association
of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute
kidney injury in subjects without immunodeficiency or autoimmunity. STUDY DESIGN:
Stimulated by our experience with two cases, we performed a review of the
literature. RESULTS: The literature documents 38 cases (26 male and 12 female
individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic
primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney
injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7
myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal
replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not
resolve in one patient with acute interstitial nephritis. Two patients died
because of systemic complications. The remaining 35 cases fully recovered.
CONCLUSIONS: In individuals with acute symptomatic Epstein-Barr virus infectious
mononucleosis, a relevant kidney injury is rare but the outcome potentially
fatal. It results from interstitial nephritis, myositis-associated acute kidney
injury, hemolytic uremic syndrome or jaundice-associated nephropathy.
PMID- 28410497
TI - Anesthetics mechanism on a DMPC lipid membrane model: Insights from molecular
dynamics simulations.
AB - To provide insight into the molecular mechanisms of local anesthetic action, we
have carried out an extensive investigation of two amide type local anesthetics,
lidocaine and articaine in both charged and uncharged forms, interacting with
DMPC lipid membrane. We have applied both standard molecular dynamics simulations
and metadynamics simulations to provide a detailed description of the free energy
landscape of anesthetics embedded in the lipid bilayer. The global minimum of the
free energy surface (equilibrium position of anesthetics in the lipid membrane)
occurred around 1nm of the bilayer center. The uncharged anesthetics show more
affinity to bind to this region compared to the charged drugs. The binding free
energy of uncharged lidocaine in the membrane (-30.3kJ/mol) is higher than
uncharged articaine (-24.0kJ/mol), which is in good agreement with higher lipid
solubility of lidocaine relative to the articaine. The octanol/water partition
coefficient of uncharged drugs was also investigated using expanded ensemble
simulations. In addition, complementary standard MD simulations were carried out
to study the partitioning behavior of multiple anesthetics inside the lipid
bilayer. The results obtained here are in line with previously reported
simulations and suggest that the different forms of anesthetics induce different
structural modifications in the lipid bilayer, which can provide new insights
into their complex membrane translocation phenomena.
PMID- 28410498
TI - SmartStart: Results of a large point of entry study into preloading alcohol and
associated behaviours.
AB - BACKGROUND: There is a growing trend of preloading with alcohol before entering
entertainment districts. It is claimed that this occurs to save money and that
preloading may be a good indicator of harmful drinking and risk taking behaviours
more generally. No study has collected data from a large sample as the
participants entered entertainment districts and measured blood alcohol
concentration (BAC) levels and self-reported drinking and risk taking behaviours
in a systematic way. METHODS: In this research, police and academics worked
together to gauge the breadth and depth of preloading behaviours. In all, 3039
people completed a questionnaire and were breathalysed as they entered
entertainment districts in Queensland, Australia. Of those, 2751 represented
people from Brisbane and this data, collected every Thursday night to Sunday
morning during the warm months, was analysed. RESULTS: More than 79% of people
reported to preload and 71% returned a BAC greater than zero, both with little
difference between the genders. Of preloaders, the mean BAC was 0.071, with 'to
socialise with friends' being the primary reason given for preloading. Increasing
preloading BAC was related to increasing risk taking and antisocial behaviours,
as well as alcohol abuse and dependence. Older people entering entertainment
districts had more accurate estimates of their BAC, yet 20% of our sample did not
understand how the BAC system worked. Conducting the research was associated with
a higher access rate to police and a lower arrest rate in the areas of data
collection in comparison to the same nights 1year earlier. CONCLUSION: Preloading
is widespread and involves moderate to heavy drinking in the Australian
population visiting entertainment districts. Any interventions to curb drinking
behaviours and reduce violence in night time entertainment districts need to
involve approaches aimed at cultural phenomena, such as preloading behaviours.
PMID- 28410499
TI - Comparing the impact of ultrafine particles from petrodiesel and biodiesel
combustion to bacterial metabolism by targeted HPLC-MS/MS metabolic profiling.
AB - Alterations of gut bacterial metabolism play an important role in their host
metabolism, and can result in diseases such as obesity and diabetes. While many
factors were discovered influencing the gut bacterial metabolism, exposure to
ultrafine particles (UFPs) from engine combustions were recently proposed to be a
potential risk factor for the perturbation of gut bacterial metabolism, and
consequentially to obesity and diabetes development. This study focused on
evaluation of how UFPs from diesel engine combustions impact gut bacterial
metabolism. We hypothesize that UFPs from different type of diesel (petrodiesel
vs. biodiesel) will both impact bacterial metabolism, and the degree of impact is
also diesel type-dependent. Targeted metabolic profiling of 221 metabolites were
applied to three model gut bacteria in vitro, Streptococcus salivarius,
Lactobacillus acidophilus and Lactobacillus fermentum. UFPs from two types of
fuels, petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by
volume), were exposed to the bacteria and their metabolic changes were compared.
For each bacterial strain, metabolites with significantly changed abundance were
observed in both perturbations, and all three strains have increased number of
altered metabolites detected from B20 UFPs perturbation in comparison to B0 UFPs.
Multivariate statistical analysis further confirmed that the metabolic profiles
were clearly different between testing groups. Metabolic pathway analyses also
demonstrated several important metabolic pathways, including pathways involves
amino acids biosynthesis and sugar metabolism, were significantly impacted by
UFPs exposure.
PMID- 28410500
TI - Cancer is a propagandist.
AB - Communication among cells (also known as cross-talk) plays a prominent role in
the current knowledge of the pathophysiology of cancer and of cancer-associated
conditions such as paraneoplastic syndromes and cachexia that are responsible for
much of cancer's morbidity and mortality. Yet, biomedical scientists lack an
explicit unifying frame that places this exchange of molecular information at the
core of their understanding of cancer as a systemic disease. Propaganda is a type
of information that aims at misleading, a form of communication intended
primarily to serve the messenger. The biased molecular cross-talk between cancer
and non-cancer cells can be considered as a form of biological propaganda. I here
propose cancer is a propagandist as a metaphor that may serve as a unifying frame
to interpret both cancer and cancer-associated syndromes under the same
communication-based concept and may thus serve to bring together research that is
currently compartmentalized under separate disciplines.
PMID- 28410501
TI - Comparison of gene expression profiles induced by fresh or ozone-oxidized black
carbon particles in A549 cells.
AB - Epidemiological studies have showed an association between black carbon (BC)
exposure and adverse health effects. This study intends to investigate the
influence of oxidation processes in atmosphere on the initial cellular responses
of BC. The changes of gene expressions induced by fresh BC (FBC) and ozone
oxidized BC (OBC) in human lung epithelial A549 cells were analyzed. And their
toxic effects presented by viability, LDH release and DNA damage were compared.
Totally 47, 000 genes in A549 cells were examined using Affymetrix Human U133
plus 2.0 chips. Some of the differentially expressed genes were verified by
reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The
results showed that 1446 genes (including 756 up-regulated and 690 down
regulated) and 1594 genes (including 788 up-regulated and 806 down-regulated
genes) were significantly changed by FBC and OBC respectively. Only 4 of 14
(FBC)/15 (OBC) oxidative stress related genes, up- or down-regulated by FBC and
OBC, were identical; 13 of 29 (FBC)/31 (OBC) inflammation related genes, and 6 of
20 (FBC)/18 (OBC) autophagy related genes were identical. No obvious differences
were observed between the toxic effects of FBC and OBC. The cytotoxicity of OBC
and FBC in A549 cells is at least partially induced by oxidative stress and
consequent inflammation or autophagy process. Previous studies indicated that OBC
may be more toxic than FBC. However, our results suggested that FBC and OBC might
lead to diverse toxic endpoints through activating different molecular pathways.
PMID- 28410502
TI - Importance of allochthonous and autochthonous dissolved organic matter in Fe(II)
oxidation: A case study in Shizugawa Bay watershed, Japan.
AB - Ferrous iron (Fe[II]) oxidation by dissolved oxygen was investigated in the
Shizugawa Bay watershed with particular attention given to the effect of
dissolved organic matter (DOM) properties on Fe(II) oxidation. To cover a wide
spectrum of DOM composition, water samples were collected from various water
sources including freshwater (e.g., river water and wastewater effluent) and
coastal seawater. Measurement of nanomolar Fe(II) oxidation by using luminol
chemiluminescence under dark, air-saturated conditions at 25 degrees C indicated
that spatio-temporal variation of the second-order rate constant (6.7-74.5 M-1 s
1) was partially explained by the variation of the sample pH (7.5-8.6). However,
at comparable pH values, the oxidation rates for freshwater were generally
greater than those for coastal seawater. The substantial decline in oxidation
rate constant after the removal of humic-type (allochthonous) DOM suggested that
this hydrophobic DOM is a key factor that accelerates the Fe(II) oxidation in the
freshwater samples. Observed lower oxidation rates for coastal seawater compared
with freshwater and organic ligand-free seawater were likely associated with
microbially derived autochthonous DOM, and the variation of Fe(II) oxidation at a
fixed pH was best described by fluorescence index that represents the proportion
of autochthonous and allochthonous DOM in natural waters. Consistently, Fe(II)
oxidation was found to be slower in the presence of cellular exudates from
phytoplankton. The present study highlighted the significant effect of DOM
composition on the Fe(II) oxidation in inland and coastal waters.
PMID- 28410503
TI - Continuous micro-current stimulation to upgrade methanolic wastewater
biodegradation and biomethane recovery in an upflow anaerobic sludge blanket
(UASB) reactor.
AB - The dispersion of granules in upflow anaerobic sludge blanket (UASB) reactor
represents a critical technical issue in methanolic wastewater treatment. In this
study, the potentials of coupling a microbial electrolysis cell (MEC) into an
UASB reactor for improving methanolic wastewater biodegradation, long-term
process stability and biomethane recovery were evaluated. The results indicated
that coupling a MEC system was capable of improving the overall performance of
UASB reactor for methanolic wastewater treatment. The combined system maintained
the comparatively higher methane yield and COD removal efficiency over the single
UASB process through the entire process, with the methane production at the
steady-state conditions approaching 1504.7 +/- 92.2 mL-CH4 L-1-reactor d-1,
around 10.1% higher than the control UASB (i.e. 1366.4 +/- 71.0 mL-CH4 L-1
reactor d-1). The further characterizations verified that the input of external
power source could stimulate the metabolic activity of microbes and reinforced
the EPS secretion. The produced EPS interacted with Fe2+/3+ liberated during
anodic corrosion of iron electrode to create a gel-like three-dimensional [-Fe
EPS-]n matrix, which promoted cell-cell cohesion and maintained the structural
integrity of granules. Further observations via SEM and FISH analysis
demonstrated that the use of bioelectrochemical stimulation promoted the growth
and proliferation of microorganisms, which diversified the degradation routes of
methanol, convert the wasted CO2 into methane and accordingly increased the
process stability and methane productivity.
PMID- 28410504
TI - Exercise training in older adults, what effects on muscle oxygenation? A
systematic review.
AB - AIM: To determine the effects of different modality of exercise training programs
on muscle oxygenation in older adults. METHODS: Relevant articles were searched
in PubMed, Web of Science, Science Direct and Scopus, using the keywords: "Aged"
AND "Muscle oxygenation" AND (Exercise OR "Exercise therapy" OR "Exercise
Movement Techniques" OR Hydrotherapy), without limitation concerning the
publication date. To be included in the full analysis, the study had to be a
randomized controlled trial in which older adults participants (mean age: 65
years at least) were submitted to an exercise-training program and muscle
oxygenation assessment. RESULTS: The searches resulted in 1238 articles from
which 7 met all the inclusion criteria. The trials involved 370 older adults
(68.7+/-1.7years), healthy and with peripheral arterial disease. Studies included
resistance and endurance exercises as well as walking sessions. Training sessions
were 2-6 time per week, lasted 3-24 months and with different training intensity
throughout studies. After a long-term resistance training, healthy older adults
showed enhanced muscle oxygen extraction capacity, regulation of vessels and
vascular endothelium function; endurance training is reported to improve
microvascular blood flow and matching of oxygen delivery to oxygen utilization,
muscle oxidative capacity and muscle saturation, and walking sessions results in
better muscle oxygen availability and muscle oxygen extraction capacity in older
adults with peripheral arterial disease. CONCLUSIONS: This review supports the
fact that depending on the clinical status of the participants and the modality,
exercise training improves different aspects of the muscle oxygenation in older
adults.
PMID- 28410505
TI - Multi-atlas pancreas segmentation: Atlas selection based on vessel structure.
AB - Automated organ segmentation from medical images is an indispensable component
for clinical applications such as computer-aided diagnosis (CAD) and computer
assisted surgery (CAS). We utilize a multi-atlas segmentation scheme, which has
recently been used in different approaches in the literature to achieve more
accurate and robust segmentation of anatomical structures in computed tomography
(CT) volume data. Among abdominal organs, the pancreas has large inter-patient
variability in its position, size and shape. Moreover, the CT intensity of the
pancreas closely resembles adjacent tissues, rendering its segmentation a
challenging task. Due to this, conventional intensity-based atlas selection for
pancreas segmentation often fails to select atlases that are similar in pancreas
position and shape to those of the unlabeled target volume. In this paper, we
propose a new atlas selection strategy based on vessel structure around the
pancreatic tissue and demonstrate its application to a multi-atlas pancreas
segmentation. Our method utilizes vessel structure around the pancreas to select
atlases with high pancreatic resemblance to the unlabeled volume. Also, we
investigate two types of applications of the vessel structure information to the
atlas selection. Our segmentations were evaluated on 150 abdominal contrast
enhanced CT volumes. The experimental results showed that our approach can
segment the pancreas with an average Jaccard index of 66.3% and an average Dice
overlap coefficient of 78.5%.
PMID- 28410506
TI - Inhibitory effect of Campomanesia xanthocarpa in platelet aggregation: Comparison
and synergism with acetylsalicylic acid.
AB - BACKGROUND AND AIMS: Cardiovascular diseases of thrombotic origin are related to
high mortality and standard therapeutic agent used in this case is
acetylsalicylic acid (ASA), but serious adverse events may occur. However, recent
data has suggested the plant Campomanesia xanthocarpa has antiplatelet activity
and could be a viable alternative. In this study we investigated the effects of
the encapsulated powder of this plant in human platelet aggregation. METHODS: 23
healthy subjects were randomly divided into three groups: (1) ASA (100mg), (2) C.
xanthocarpa (1000mg) or (3) synergism (500mg of C. xanthocarpa plush 50mg of
ASA); daily for five days. Antiplatelet activity was determined by turbidimetric
method using ADP or arachidonic acid (AA) agonists before, 5 and 8days after
treatments. RESULTS: Treatment with C. xanthocarpa and synergism caused a
reduction of 8+/-13.5% and 12.5+/-5% in platelet aggregation induced by ADP after
5days of treatment, respectively, returning to basal levels after 8days. For AA
agonist, 5days of treatment with C. xanthocarpa, ASA or synergism caused a
reduction of 46+/-15%, 36+/-12% and 69.3+/-6% in platelet aggregation,
respectively, and first two groups returned to baseline values 8days after
treatment ended. Synergism group prolonged antiplatelet effect maintaining
aggregation reduction after 8days the end of treatment. CONCLUSION: C.
xanthocarpa showed antiplatelet action when stimulated by agonist AA, and
contributed to the antiplatelet effect when associated with ASA for both
agonists, allowing dose reduction to 50mg.
PMID- 28410507
TI - High level of IL-10 expression in the blood of animal models possibly relates to
resistance against leptospirosis.
AB - Leptospirosis is a severe zoonosis which immunopathogenesis is poorly understood.
We evaluated correlation between acute form of the disease and the ratio of the
anti-inflammatory cytokine IL-10 to the pro-inflammatory TNF-alpha and IL-1beta
expression during the early phase of infection comparing resistant mice and
susceptible hamsters infected with two different species of virulent Leptospira.
The IL-10/TNF-alpha and IL-10/IL-1beta expression ratios were higher in mouse
compared to hamster independently of the Leptospira strain, suggesting a
preponderant role of the host response and notably these cytokines in the
clinical expression and survival to leptospirosis. Using an IL-10 neutralization
strategy in Leptospira-infected mouse model, we also showed evidence of a
possible role of this cytokine on host susceptibility, bacterial clearance and on
regulation of cytokine gene expression.
PMID- 28410508
TI - Around the macrolide - Impact of 3D structure of macrocycles on lipophilicity and
cellular accumulation.
AB - The aim of this study was to investigate lipophilicity and cellular accumulation
of rationally designed azithromycin and clarithromycin derivatives at the
molecular level. The effect of substitution site and substituent properties on a
global physico-chemical profile and cellular accumulation of investigated
compounds was studied using calculated structural parameters as well as
experimentally determined lipophilicity. In silico models based on the 3D
structure of molecules were generated to investigate conformational effect on
studied properties and to enable prediction of lipophilicity and cellular
accumulation for this class of molecules based on non-empirical parameters. The
applicability of developed models was explored on a validation and test sets and
compared with previously developed empirical models.
PMID- 28410509
TI - Effects of atmospheric reactive phosphorus deposition on phosphorus transport in
a subtropical watershed: A Chinese case study.
AB - Atmospheric phosphorus (P) deposition is not only an important external
macronutrient source for aquatic ecosystems but also a major cause of high export
coefficient (EC) values. However, there are limited numbers of studies in the
literature that focus on estimating the deposition flux of reactive P (Pr). The
aim of this study is to estimate the Pr deposition on the Xiangxi River
watershed, and therefore, provide a comprehensive understanding about the Pr
deposition on subtropical watersheds in China. Results have shown that maximal Pr
deposition fluxes reached 12 kg km-2 in our selected subtropical watershed.
Furthermore, we found out the particulate phosphorus (PP) were dominating the
total Pr deposition in the Xiangxi River watershed. According to our experiments,
certain forms of Pr deposition were associated with high correlation coefficients
with respect to the variation of rainfall intensity. Results also demonstrated
that the dissolved organic phosphorus (DOP) and soluble reactive phosphorus (SRP)
via wet deposition had large influences on the DOP and SRP concentrations in
runoff, while the PO4-P and PP via wet deposition only affected PO4-P and PP
loads through runoff discharge. Our experiments also shown that most parts of the
Pr in runoff water was derived from rainfall and its magnitudes varied with land
types. Results suggested that during the dry season, the Pr wet deposition not
only was an important source for the Pr transport driven by runoff, but also was
one of the most important influencing factors that dominated the Pr transport in
subtropical watersheds.
PMID- 28410510
TI - Tourniquet application after local forearm warming to improve venodilation for
peripheral intravenous cannulation in young and middle-aged adults: A single
blind prospective randomized controlled trial.
AB - BACKGROUND: Local forearm warming before tourniquet application is often used to
promote venodilation for peripheral intravenous cannulation; however, few studies
have compared the effect of tourniquet application with and without local warming
on vein size. OBJECTIVE: To evaluate the effectiveness of tourniquet application
after local forearm warming with that of tourniquet application alone in young
and middle-aged adults. DESIGN: A single-blind, prospective, parallel group,
randomized controlled trial. SETTING: A national university in Japan.
PARTICIPANTS: Seventy-two volunteers aged 20-64 years. METHODS: Participants were
randomly allocated to one of two groups: tourniquet application for 30s after
forearm application of a heat pack warmed to 40 degrees C+/-2 degrees C for 15min
(active warming group; n=36) or tourniquet application for 30s after applying a
non-warmed heat pack for 15min (passive warming group; n=36). The primary
outcomes were vein cross-sectional area on the forearm, measured after the
intervention by blinded research assistants using ultrasound. Secondary outcomes
were shortest diameter, and longest diameter of vein on the forearm, forearm skin
temperature, body temperature, pulse, systolic blood pressure, and diastolic
blood pressure. All outcomes were assessed at the same site before and
immediately after the intervention, once per participant. RESULTS: Vein cross
sectional area, shortest vein diameter, and longest vein diameter were
significantly increased in the active warming group compared with the passive
warming group (p <0.01). Tourniquet application after local warming was superior
to tourniquet application alone in increasing vein cross-sectional, shortest
diameter, and longest diameter (between-group differences of 2.2mm2, 0.5mm, and
0.5mm, respectively), and in raising skin temperature (between-group difference:
5.2 degrees C). However, there were no significant differences in body
temperature, pulse, or systolic or diastolic blood pressure between the groups.
There were no adverse events associated with either intervention. CONCLUSION:
Tourniquet application after local warming was associated with increased forearm
vein size when compared with tourniquet application alone, and was demonstrated
as being safe. Thus, with demonstrable effects on vein size, we recommend local
warming before tourniquet application as a safe and effective technique for
improving venodilation.
PMID- 28410511
TI - Evaluation of intraventricular colistin utilization: A case series.
AB - PURPOSE: Multi-drug resistant organisms (MDROs) are an increasing concern in
health systems. Pathogens such as Pseudomonas aeruginosa, Acinetobacter baumanii,
and carbapenamase-producing Enterobacteriaceae hold highest mortality rates
especially when the central nervous system is involved. When MDROs are cultured
treatment options are limited and reliance on medications such as colistin is
becoming more prevalent. Penetration of these therapies into the central nervous
system is concerning therefore local administration is a potential concomitant
therapy. METHODS: This study was a retrospective review from 2009 to 2015 for all
patients with documented MDROs gram negative pathogens who received
intraventricular colistin. RESULTS: Seven patients met inclusion criteria. The
average age of the patients was 49years old, 4 were males, and the median length
of intensive care unit stay was 30days. The duration of therapy ranged from 2 to
14days and all cerebrospinal fluid cultures were sterile at 7days after
administration of colistin. Six of the seven patients were discharged from the
hospital and one discharged to a skilled nursing facility. The use of
intraventricular colistin was not associated with any reported adverse events.
CONCLUSION: The use of intraventricular colistin was associated with positive
clinical outcomes with no reported adverse effects.
PMID- 28410512
TI - Hydronium jarosite activation of peroxymonosulfate for the oxidation of organic
contaminant in an electrochemical reactor driven by microbial fuel cell.
AB - Electro-assisted Fenton-like (EAFL) system based on sulfate radicals (SO4-) has
been extensively explored for the degradation of recalcitrant organic
contaminant. Nevertheless, external power supply should be provided
uninterruptedly in the EAFL process and thus the high energy consumption is
ineluctable. Recently, microbial fuel cell (MFC), a bio-electrochemical system
where exoelectricigens are used to catalyze fuels into electricity energy has
gained popularity mainly due to its renewability. Herein, a novel heterogeneous
EAFL system, hydronium jarosite (HJ) activation of peroxymonosulfate (PMS) in an
electrochemical reactor driven by an uncoated single-chamber MFC (MFC/HJ/PMS),
was employed to decolorize acid orange 7 (AO7). The results suggest that the
MFC/HJ/PMS system can remove AO7 efficiently in a wide pH range (3-9). The
concentration of total iron leached could meet European Union discharge standards
and hydronium jarosite could be used at least three circles. The results of
electron paramagnetic resonance analysis and radical scavenging experiments
indicate SO4- is the major active species responsible for the AO7 elimination.
The work provides an efficient, energy-saving and cost-effective approach to
treat organic wastewater and develops the conceivable utilization of hydronium
jarosite, precipitates produced in hydrometallurgical process.
PMID- 28410513
TI - Representation learning via Dual-Autoencoder for recommendation.
AB - Recommendation has provoked vast amount of attention and research in recent
decades. Most previous works employ matrix factorization techniques to learn the
latent factors of users and items. And many subsequent works consider external
information, e.g., social relationships of users and items' attributions, to
improve the recommendation performance under the matrix factorization framework.
However, matrix factorization methods may not make full use of the limited
information from rating or check-in matrices, and achieve unsatisfying results.
Recently, deep learning has proven able to learn good representation in natural
language processing, image classification, and so on. Along this line, we propose
a new representation learning framework called Recommendation via Dual
Autoencoder (ReDa). In this framework, we simultaneously learn the new hidden
representations of users and items using autoencoders, and minimize the
deviations of training data by the learnt representations of users and items.
Based on this framework, we develop a gradient descent method to learn hidden
representations. Extensive experiments conducted on several real-world data sets
demonstrate the effectiveness of our proposed method compared with state-of-the
art matrix factorization based methods.
PMID- 28410514
TI - Age estimation in adults by dental imaging assessment systematic review.
AB - IMPORTANCE: The need to rely on proper, simple, and accurate methods for age
estimation in adults is still a world-wide issue. It has been well documented
that teeth are more resistant than bones to the taphonomic processes, and that
the use of methods for age estimation based on dental imaging assessment are not
only less invasive than those based on osseous analysis, but also have shown
similar or superior accuracy in adults. OBJECTIVES: To summarise the results of
some of the recently most recently cited methods for dental age estimation in
adults, based on odontometric dental imaging analysis, to establish which is more
accurate, accessible, and simple. EVIDENCE REVIEW: A literature search from
several databases was conducted from January 1995 to July 2016 with previously
defined inclusion criteria. CONCLUSION: Based on the findings of this review, it
could be possible to suggest pulp/tooth area ratio calculation from first, upper
canines and other single rooted teeth (lower premolars, upper central incisors),
and a specific statistical analysis that considers the non-linear production of
secondary dentine with age, as a reliable, easy, faster, and predictable method
for dental age estimation in adults. The second recommended method is the
pulp/tooth width-length ratio calculation. The use of specific population
formulae is recommended, but to include data of individuals from different groups
of population in the same analysis is not discouraged. A minimum sample size of
at least 120 participants is recommended to obtain more reliable results. Methods
based on volume calculation are time consuming and still need improvement.
PMID- 28410515
TI - Folate receptor-targeted hybrid lipid-core nanocapsules for sequential delivery
of doxorubicin and tanespimycin.
AB - When exposed to cancer cells, cytotoxic drugs such as doxorubicin (DOX) can lead
to the induction of heat shock protein 90 (Hsp90), a molecular chaperone
associated with a number of cancer-related client proteins, and result in cell
survival. Co-administration of DOX with tanespimycin (TNP), an Hsp90 inhibitor,
can sensitize the cancer cells to the cytotoxic effects of DOX. The effect of
such a combination has been found to depend on the schedule of administration.
Sequential administration of DOX and TNP has been linked to highly synergistic
combination effects. Therefore, we aimed to develop folate-receptor targeted
hybrid lipid-core nanocapsules comprising a hybrid lipid core lodging TNP and a
polymeric corona lodging DOX (F-DTN). These nanocarriers were capable of
delivering DOX and TNP sequentially, which was well demonstrated by an in vitro
release study. The in vitro release profiles displayed pH-dependent and sustained
release features. F-DTN exhibited excellent morphological characteristics with
highly monodispersed particles. In vitro tests with F-DTN in MCF-7 cell line
demonstrated exceptional cytotoxicity, with high cellular uptake and apoptosis.
These findings were appreciably more assertive than tests with free individual
drugs (DOX, TNP), free drug combination (DOX/TNP), or non-folate receptor
targeted hybrid lipid-core nanocapsules (DTN). In vivo pharmacokinetic study
revealed noticeable enhancement of bioavailability and plasma circulation time of
the drugs when encapsulated in the carrier system. Therefore, hybrid lipid-core
nanocapsules have the potential to be utilized for application in folate receptor
targeted combination chemotherapy.
PMID- 28410516
TI - Environmental knowledge and attitudes and behaviours towards energy consumption.
AB - Numerous investigations have arisen in order to study and characterise
environmentally friendly consumer profiles, with some authors applying the
relationship between knowledge, attitudes and behaviour to this end. The present
research approach, based upon the Theory of Reasoned Action (TRA), seeks to
verify the existence of relationships between knowledge and attitudes and between
knowledge and environmental behaviour. In this instance, data collection involved
a questionnaire aimed at assessing the overall environmental knowledge of
respondents as well as their attitudes and behaviours regarding energy issues
(savings, consumption, interest, use). The results pointed to the lack of
relationship between knowledge and attitudes, and between knowledge and behaviour
whilst the relationship between attitudes and behaviour proved to be only weak.
The results also found that males, older students and those studying Engineering
and the Social and Human Sciences are those reporting higher levels of
environmental knowledge. However, when it comes to attitudes and behaviours,
females seem to display more awareness around these issues.
PMID- 28410517
TI - Effect of the acid treatment conditions of kaolinite on etheramine adsorption: A
comparative analysis using chemometric tools.
AB - The present work evaluated the effect of the acid treatment conditions of natural
kaolinite (NK) regarding its efficiency in removing etheramine. The treatment was
conducted using sulfuric acid at the concentrations of 1 mol L-1 (KA-01), 2 mol L
1 (KA-02) and 5 mol L-1 (KA-05) at 85 degrees C. The obtained adsorbents were
characterized by X-ray fluorescence, X-ray diffraction, N2 adsorption/desorption
isotherms, zeta potential analysis and infrared spectroscopy. The Response
Surface Method was used to optimize adsorption parameters (initial concentration
of etheramine, adsorbent mass and pH of the solution). The results, described by
means of a central composite design, were adjusted to the quadratic model.
Results revealed that the adsorption was more efficient at the etheramine
concentration of 400 mg L-1, pH 10 and adsorbent mass of 0.1 g for NK and 0.2 g
for KA-01, KA-02 and KA-05. The sample KA-02 presented a significant increase of
etheramine removal compared to the NK sample. The adsorption kinetics conducted
under optimized conditions showed that the system reached the equilibrium in
approximately 30 min. The kinetic data were better adjusted to the pseudo-second
order model. The isotherm data revealed that the Sips model was the most adequate
one. The calculation of Eads allowed to infer that the mechanism for etheramine
removal in all the evaluated samples was chemisorption. The reuse tests showed
that, after four uses, the efficiency of adsorbents in removing etheramine did
not suffer significant modifications, which makes the use of kaolinite to treat
effluents from the reverse flotation of iron ore feasible.
PMID- 28410518
TI - Interactive effects of specific fine particulate matter compositions and airborne
pollen on frequency of clinic visits for pollinosis in Fukuoka, Japan.
AB - BACKGROUND: Previous studies have revealed the interactive effects of airborne
pollen and particulate matter on the daily consultations for pollinosis, but it
is uncertain which compositions are responsible. This study aimed to investigate
the interactive effects of specific PM2.5 compositions and airborne pollen on the
daily number of clinic visits for pollinosis in Fukuoka. METHODS: We obtained
daily data on pollen concentrations, PM2.5 compositions, PM2.5 mass, gaseous
pollutants (SO2, NO2, CO, and O3), and weather variables monitored in Fukuoka
between February and April, 2002-2012. In total, 73,995 clinic visits for
pollinosis were made at 10 clinics in Fukuoka Prefecture during the study period.
A time-stratified case-crossover design was applied to examine the interactive
effects. The concentrations of PM2.5 and its compositions were stratified into
low (<15th percentile), moderate (15th-85th percentile), and high (>85th
percentile) levels, and the association between airborne pollen and daily clinic
visits for pollinosis was analyzed within each level. RESULTS: We found a
significant interaction between specific PM2.5 compositions and airborne pollen.
Specifically, the odds ratio of daily clinic visits for pollinosis per
interquartile increase in pollen concentration (39.8 grains/cm2) at the average
cumulative lag of 0 and 2 days during high levels of non-sea-salt Ca2+ was 1.446
(95% CI: 1.323-1.581), compared to 1.075 (95% CI: 1.067-1.083) when only moderate
levels were observed. This result remained significant when other air pollutants
were incorporated into the model and was fairly persistent even when different
percentile cut-off points were used. A similar interaction was found when we
stratified the data according to non-sea-salt SO42- levels. This finding differed
from estimates made according to PM2.5 and NO3- levels, which predicted that the
effects of pollen were strongest in the lower levels. CONCLUSIONS: Associations
between airborne pollen and daily clinic visits for pollinosis could be enhanced
by high levels of specific PM2.5 compositions, especially non-sea-salt Ca2+.
PMID- 28410519
TI - In utero exposure to atrazine analytes and early menarche in the Avon
Longitudinal Study of Parents and Children Cohort.
AB - BACKGROUND: Evidence from experimental studies suggests that atrazine and its
analytes alter the timing of puberty in laboratory animals. Such associations
have not been investigated in humans. OBJECTIVE: To determine the association
between in utero exposure to atrazine analytes and earlier menarche attainment in
a nested case-control study of the population-based Avon Longitudinal Study of
Parents and Children. METHODS: Cases were girls who reported menarche before 11.5
years while controls were girls who reported menarche at or after 11.5 years.
Seven atrazine analyte concentrations were measured in maternal gestational urine
samples (sample gestation week median (IQR): 12 (8-17)) during the period 1991
1992, for 174 cases and 195 controls using high performance liquid chromatography
tandem mass spectrometry. We evaluated the study association using multivariate
logistic regression, adjusting for potential confounders. We used multiple
imputation to impute missing confounder data for 29% of the study participants.
RESULTS: Diaminochlorotriazine (DACT) was the most frequently detected analyte
(58%>limit of detection [LOD]) followed by desethyl atrazine (6%), desethyl
atrazine mercapturate (3%), atrazine mercapturate (1%), hydroxyl atrazine (1%),
atrazine (1%) and desisopropyl atrazine (0.5%). Because of low detection of other
analytes, only DACT was included in the exposure-outcome analyses. The adjusted
odds of early menarche for girls with DACT exposures>=median was 1.13 (95%
Confidence Interval [95% CI]:0.82, 1.55) and exposure=median was 1.86 (95% CI: 1.03, 3.38) and exposure=65years) were included. Using a previously validated enhanced optical motion
capture approach, sagittal and frontal plane spinal curvature angles and general
trunk kinematics were measured during shod walking at a self-selected normal
speed. Postural differences indicated that lumbar lordosis and thoracic kyphosis
increase throughout adolescence and reach their peak in adulthood. The absence of
excessive thoracic kyphosis in older individuals could be explained by a
previously reported subdivision in those who develop excessive kyphosis and those
who maintain their curve. Furthermore, adults displayed increased lumbar spine
range of motion as compared to the adolescents, whereas the increased values in
older individuals were found to be related to higher gait speeds. This dataset on
the age-related kinematics of the healthy spine can serve as a basis for
understanding pathological deviations and monitoring rehabilitation progression.
PMID- 28410536
TI - The influence of ball-swing on the timing and coordination of a natural
interceptive task.
AB - Successful interception relies on the use of perceptual information to accurately
guide an efficient movement strategy that allows performers to be placed at the
right place at the right time. Although previous studies have highlighted the
differences in the timing and coordination of movement that underpin interceptive
expertise, very little is known about how these movement patterns are adapted
when intercepting targets that follow a curvilinear flight-path. The aim of this
study was to examine how curvilinear ball-trajectories influence movement
patterns when intercepting a fast-moving target. Movement timing and coordination
was examined when four groups of cricket batters, who differed in their skill
level and/or age, hit targets that followed straight or curvilinear flight-paths.
The results revealed that when compared to hitting straight trials, (i) mixing
straight with curvilinear trials altered movement coordination and when the ball
was hit, (ii) curvilinear trajectories reduced interceptive performance and
significantly delayed the timing of all kinematic moments, but there were (iii)
larger decrease in performance when the ball swung away from (rather than in
towards) the performer. Movement coordination differed between skill but not age
groups, suggesting that skill-appropriate movement patterns that are apparent in
adults may have fully emerged by late adolescence.
PMID- 28410537
TI - Prediction of intra-abdominal adhesions using the visceral slide test: A
prospective observational study.
AB - OBJECTIVE: The goal of this study was to determine whether the visceral slide
test is an effective screening method for the prediction of intra-abdominal
adhesions. STUDY DESIGN: A prospective, observational study was conducted
assessing a cohort of women undergoing benign gynaecologic surgery between April
2015 and June 2015. At the patient's preoperative visit, they underwent the
ultrasound-based visceral slide test in five zones of the abdomen. The ultrasound
assessments were validated against direct visualization during surgery. The
effectiveness of the slide test as a screening technique was examined by
recording the presence, extent, and severity of adhesions observed
intraoperatively; this was scored using a modified version of the American
Fertility Society (mAFS) system. RESULTS: In total, 144 women completed the
study, 33 (22.9%) of whom had previously undergone intra-abdominal surgery. The
median time to perform the visceral slide test was 2min, and using our
methodology, 48 patients (33.3%) were diagnosed with adhesions. We found that the
visceral slide test had a sensitivity of 97.2%, specificity of 68.6%, positive
predictive value of 90.6%, negative predictive value of 88.9%, and diagnostic
accuracy of 90.3%. Further, the number of negative visceral slide tests was
positively correlated with the mAFS scores. CONCLUSION: Our data suggest that the
visceral slide test is a simple, fast, reliable assay for detecting intra
abdominal adhesions in patients undergoing gynaecologic surgery.
PMID- 28410538
TI - Synthesis of Co3O4 nanoclusters via an EDTANa4-assisted route for enhanced
electrochemical application.
AB - Three-dimensional (3D) Co3O4 nanoclusters were fabricated with the assistance of
tetrasodium ethylene diamine tetraacetic acid (EDTANa4) through a one-pot wet
chemical reaction, featuring self-limiting assembly of building blocks and
controlled regrowth process. The molar ratio of Co2+ and EDTANa4 plays a key role
in building initial clusters as blocks, and the amount of NaOH effects the
regrowth process. A possible formation mechanism for the Co3O4 nanoclusters was
proposed based on the characterization results of X-ray diffraction (XRD),
Fourier-transform infrared (FT-IR) spectroscopy and scanning electron microscopy
(SEM). The designed hierarchical Co3O4 nanoclusters exhibit a high specific
capacitance of 221Fg-1 at a current density of 2Ag-1 in 2molL-1 KOH electrolyte.
PMID- 28410539
TI - Solid-state ionics method fabricated centimeter level CuAu alloy nanowires:
Application in SERS.
AB - CuAu alloy nanowires were prepared by a solid-state ionics method under a direct
current electric field (DCEF) using fast ionic conductor Rb4Cu16Cl13I7 films. The
surface morphology, chemical composition and crystal structures of the CuAu alloy
nanowires were characterized by scanning electron microscopy (SEM), energy
dispersive spectrometer (EDS) and X-ray diffraction (XRD), respectively. Raman
enhancement performance of the CuAu alloy nanowires substrates was detected by
Rhodamine 6G (R6G) aqueous solutions as probe molecules. Long-range disorder and
short-range order CuAu alloy nanowires with the length of 1 cm were prepared by a
solid-state ionics method. The nanowires were bamboo-shaped and the diameters of
nanowires ranged from 40 to 100nm. The molar ratio of Cu to Au is 16:1. The
crystal structure of the CuAu alloy nanowires is crystallized. A part of Cu and
Au formed Au3Cu alloy structure. The limiting concentrations of R6G for the
prepared CuAu alloy nanowires SERS substrates is 10-15mol/L.
PMID- 28410540
TI - Moderated surface defects of Ni particles encapsulated with NiO nanofibers as
supercapacitor with high capacitance and energy density.
AB - Nickel oxide is a promising material for supercapacitors owing to its high
theoretical specific capacitance; however, its practical capacitance is far below
the theoretical limit. In this work, we report a novel Ni/NiO composite supported
by carbon nanofibers as a pseudocapacitor electrode. Characterization of this
sample by X-ray diffraction, transmission electron microscopy, scanning electron
microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller analysis,
and contact angle measurements revealed that Ni nanoparticles were uniformly
dispersed on the surface of the nanofibers, leading to strong metal-metal oxide
interactions and the formation of oxygen vacancies. Such three dimensional hetero
Ni/NiO components afford high conductivity owing to efficient electron transport
and abundant surface defects (oxygen vacancies), which result in enhanced
supercapacitor performance and energy density (ED). A moderate concentration of
oxygen vacancies is crucial for achieving optimized electrochemical activity. As
prepared Ni/NiO-3 nanofibers generated high capacitances of 526 and 400F/g at
current densities of 1 and 10A/g, respectively, with good stability (80% of the
initial capacitance retained after 1000 cycles). Moreover, an ED as high as
65.8Wh/kg was achieved at a power density of 900W/kg, which is higher than those
of NiO-based supercapacitors. This work provides a strategy for improving the
potential of metal oxides for energy storage applications.
PMID- 28410541
TI - The influence of a novel two dimensional graphene-like nanomaterial on thermal
stability and flammability of polystyrene.
AB - Significant improvements in thermal stability and fire resistance properties of
polymer materials with nanofillers at low loadings hold tremendous promise for
fire safety materials. In this study, a novel two dimensional (2D) graphene-like
nanomaterial (VOP) was synthesized by a simple refluxing method and then modified
with typical organic surfactants. Subsequently, the novel graphene-like
nanomaterials were incorporated into polystyrene (PS) matrix for reducing fire
hazards. The SEM and TEM images indicated that the VOP nanosheets were well
dispersed throughout the matrix without obvious aggregates, leading to remarkable
improvements of thermal stability and fire safety properties. With the loading of
1wt% modified VOP, the T5%, T10%, T50% and Tmax values were increased by 15, 22,
29 and 33 degrees C, respectively. In addition, the presence of VOP nanosheets
decreased the decomposition rate of PS and increased the amount of char residues.
Furthermore, the peak heat release rate and total heat release of PS composites
was decreased by 48.3% and 43.6%, respectively, compared to that of neat PS. The
well dispersion, physical barrier effect and catalytic carbonization effect of
VOP nanosheets were the main causations for the reduction of fire hazards.
PMID- 28410542
TI - Estimation of critical supersaturation solubility ratio for predicting diameters
of dry particles prepared by air-jet atomization of solutions.
AB - Air-jet atomization of solution into droplets followed by controlled drying is
increasingly being used for producing nanoparticles for drug delivery
applications. Nanoparticle size is an important parameter that influences the
stability, bioavailability and efficacy of the drug. In air-jet atomization
technique, dry particle diameters are generally predicted by using solute
diffusion models involving the key concept of critical supersaturation solubility
ratio (Sc) that dictates the point of crust formation within the droplet. As no
reliable method exists to determine this quantity, the present study proposes an
aerosol based method to determine Sc for a given solute-solvent system and
process conditions. The feasibility has been demonstrated by conducting
experiments for stearic acid in ethanol and chloroform as well as for anti
tubercular drug isoniazid in ethanol. Sc values were estimated by combining the
experimentally observed particle and droplet diameters with simulations from a
solute diffusion model. Important findings of the study were: (i) the measured
droplet diameters systematically decreased with increasing precursor
concentration (ii) estimated Sc values were 9.3+/-0.7, 13.3+/-2.4 and 18+/-0.8
for stearic acid in chloroform, stearic acid and isoniazid in ethanol
respectively (iii) experimental results pointed at the correct interfacial
tension pre-factor to be used in theoretical estimates of Sc and (iv) results
showed a consistent evidence for the existence of induction time delay between
the attainment of theoretical Sc and crust formation. The proposed approach has
been validated by testing its predictive power for a challenge concentration
against experimental data. The study not only advances spray-drying technique by
establishing an aerosol based approach to determine Sc, but also throws
considerable light on the interfacial processes responsible for solid-phase
formation in a rapidly supersaturating system. Until satisfactory theoretical
formulae for predicting CSS are developed, the present approach appears to offer
the best option for engineering nanoparticle size through solute diffusion
models.
PMID- 28410544
TI - Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid
Responsiveness: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: The aim of fluid resuscitation is to increase stroke volume, yet this
effect is observed in only 50% of patients. Prediction of fluid responsiveness
may allow fluid resuscitation to be administered to those most likely to benefit.
The aim of this study was to systematically review the test characteristics of
respiratory variation in inferior vena cava (IVC) diameter as a predictor of
fluid responsiveness in patients with acute circulatory failure. METHODS:
Electronic searches combined with reference review of identified studies.
Prospective observational studies of all patient groups and ages that used a
recognized reference standard, stratified participants into fluid responders and
fluid non-responders, and used summary statistics to describe their results were
selected for inclusion. Study design, size, setting, patient population, use of
mechanical ventilation and tidal volume, definition of fluid responsiveness,
fluid challenge strategy, and summary statistics were abstracted. Quality
assessment was performed using the Quality Assessment of Diagnostic Accuracy
Studies-2 (QUADAS-2) domains. RESULTS: Seventeen studies involving 533 patients
were included, in whom 253 (47%) were fluid responders. The pooled sensitivity
and specificity for a positive IVC ultrasound as a predictor of fluid
responsiveness were 0.63 (95% confidence interval [CI]: 0.56-0.69) and 0.73 (95%
CI: 0.67-0.78), respectively, with a pooled area under the receiver operating
characteristic curve of 0.79 (standard error 0.05). In subgroup analysis,
respiratory variation in IVC diameter was a better predictor of fluid
responsiveness in mechanically ventilated patients. CONCLUSIONS: Respiratory
variation in IVC diameter has limited ability to predict fluid responsiveness,
particularly in spontaneously ventilating patients. A negative test cannot be
used to rule out fluid responsiveness. Clinical context should be taken into
account when using IVC ultrasound to help make treatment decisions.
PMID- 28410543
TI - Probing the prostate tumour microenvironment II: Impact of hypoxia on a cell
model of prostate cancer progression.
AB - Approximately one in six men are diagnosed with Prostate Cancer every year in the
Western world. Although it can be well managed and non-life threatening in the
early stages, over time many patients cease to respond to treatment and develop
castrate resistant prostate cancer (CRPC). CRPC represents a clinically
challenging and lethal form of prostate cancer. Progression of CRPC is, in part,
driven by the ability of cancer cells to alter their metabolic profile during the
course of tumourgenesis and metastasis so that they can survive in oxygen and
nutrient-poor environments and even withstand treatment. This work was carried
out as a continuation of a study aimed towards gaining greater mechanistic
understanding of how conditions within the tumour microenvironment impact on both
androgen sensitive (LNCaP) and androgen independent (LNCaP-abl and LNCaP-abl-Hof)
prostate cancer cell lines. Here we have applied technically robust and
reproducible label-free liquid chromatography mass spectrometry analysis for
comprehensive proteomic profiling of prostate cancer cell lines under hypoxic
conditions. This led to the identification of over 4,000 proteins - one of the
largest protein datasets for prostate cancer cell lines established to date. The
biological and clinical significance of proteins showing a significant change in
expression as result of hypoxic conditions was established. Novel, intuitive
workflows were subsequently implemented to enable robust, reproducible and high
throughput verification of selected proteins of interest. Overall, these data
suggest that this strategy supports identification of protein biomarkers of
prostate cancer progression and potential therapeutic targets for CRPC.
PMID- 28410545
TI - LPS Stimulation of Cord Blood Reveals a Newborn-Specific Neutrophil
Transcriptomic Response and Cytokine Production.
AB - BACKGROUND: The neonatal innate immune system differs to microbial infection both
quantitatively and qualitatively when compared with adults. Here, we provide the
first genome-wide ex-vivo expression profile of umbilical cord blood (UCB)
neutrophils from full-term infants prior to and in response to whole-blood
lipopolysaccharide (LPS) stimulation. Additionally, we provide cytokine
expression prior to and following LPS stimulation. The genomic expression and
cytokine profile are compared with LPS-stimulated whole blood from healthy adult
subjects (HC). METHODS: Whole blood from UCB (n = 6) and HC (n = 6) was studied
at baseline or was stimulated for 24 h with 100 ngs/mL of LPS. CD66b neutrophils
were subsequently isolated with microfluidic techniques and genome-wide
expression analyses were performed. Ingenuity Pathway Analysis (IPA) software was
utilized to predict downstream functional effects. Additionally, cytokine
concentrations in whole blood prior to and after 24 h of LPS incubation were
determined. RESULTS: LPS stimulated whole blood from UCB demonstrated significant
differences in both ex-vivo cytokine production and PMN gene expression. Mixed
effect modeling identified 1,153 genes whose expression changed significantly in
UCB and HC after exposure to LPS (P < 0.001 with a minimum 1.5-fold change). IPA
downstream predictions suggest that PMNs from UCB fail to effectively upregulate
genes associated with activation, phagocytosis, and chemotaxis in response to LPS
stimulation. Furthermore, whole blood from UCB showed increased interleukin (IL)
10 production to LPS, but failed to significantly increase several pro
inflammatory cytokines. CONCLUSIONS: LPS-stimulated whole blood from UCB
exhibited a markedly suppressed inflammatory cytokine production and PMN innate
immune genome response. These differences in gene expression and cytokine
production may be an adaptive response to a prior fetal environment, but may also
explain their increased susceptibility to infections. Characterization of these
deficits is the first step toward developing prophylactic and therapeutic
interventions.
PMID- 28410546
TI - Coinfection and Mortality in Pneumonia-Related Acute Respiratory Distress
Syndrome Patients with Bronchoalveolar Lavage: A Prospective Observational Study.
AB - BACKGROUND: Pneumonia is the leading risk factor of acute respiratory distress
syndrome (ARDS). It is increasing studies in patients with pneumonia to reveal
that coinfection with viral and bacterial infection can lead to poorer outcomes
than no coinfection. This study evaluated the role of coinfection identified
through bronchoalveolar lavage (BAL) examination on the outcomes of pneumonia
related ARDS. METHODS: We performed a prospective observational study at Chang
Gung Memorial Hospital from October 2012 to May 2015. Adult patients were
included if they met the Berlin definition of ARDS. The indications for BAL were
clinically suspected pneumonia-related ARDS and no definite microbial sample
identified from tracheal aspirate or sputum. The presence of microbial pathogens
and clinical outcomes were analyzed. RESULTS: Of the 19,936 patients screened,
902 (4.5%) fulfilled the Berlin definition of ARDS. Of these patients, 255
(22.7%) had pneumonia-related ARDS and were included for analysis. A total of 142
(55.7%) patients were identified to have a microbial pathogen through BAL and
were classified into three groups: a virus-only group (n = 41 [28.9%]), no virus
group (n = 60 [42.2%]), and coinfection group (n = 41 [28.9%]). ARDS severity did
not differ significantly between the groups (P = 0.43). The hospital mortality
rates were 53.7% in virus-only identified group, 63.3% in no virus identified
group, and 80.5% in coinfection identified group. The coinfection group had
significantly higher mortality than virus-only group (80.5% vs. 53.7%; P = 0.01).
CONCLUSION: In patients with pneumonia-related ARDS, the BAL pathogen-positive
patients had a trend of higher mortality rate than pathogen-negative patients.
Coinfection with a virus and another pathogen was associated with increased
hospital mortality in pneumonia-related ARDS patients.
PMID- 28410547
TI - Endocan Overexpression in Pterygium.
AB - PURPOSE: The aim of this study was to evaluate the possible role of endocan in
the pathogenesis of pterygium. METHODS: The study was conducted on 33 patients
with primary pterygium and 20 control subjects with normal bulbar conjunctiva.
Patients with pterygium were graded into 3 groups as atrophic, fleshy, and
intermediate, according to the Tan classification. Primary nasal pterygia and
normal bulbar conjunctivas were surgically removed. Endocan expression was
immunohistochemically investigated. RESULTS: Endocan expression in epithelial and
endothelial cells was statistically significantly higher in pterygium tissues
than control tissues (P = 0.001). No significant correlation was observed between
pterygium classification groups and endocan expression in both epithelial and
endothelial cells (P > 0.05). CONCLUSIONS: The results suggest that endocan may
have a role in the pathogenesis of pterygium.
PMID- 28410548
TI - Two-Year Clinical Outcome of 500 Consecutive Cases Undergoing Descemet Membrane
Endothelial Keratoplasty.
AB - PURPOSE: To evaluate the clinical outcome of 500 consecutive cases up to 2 years
after Descemet membrane endothelial keratoplasty (DMEK) and to assess which
parameters may have influenced the clinical outcome. METHODS: From a group of 500
eyes (393 patients), which underwent DMEK for Fuchs endothelial corneal dystrophy
(FECD), bullous keratopathy, failed corneal transplants and other indications,
clinical outcomes [best-corrected visual acuity (BCVA), central endothelial cell
density (ECD), and central corneal thickness] were evaluated before, and at 6,
12, and 24 months after DMEK and postoperative complications were documented.
RESULTS: At 12 months postoperatively, 81% of eyes reached a BCVA of >=20/25
(>=0.8), 49% >=20/20 (>=1.0), and 15% >=20/18 (>=1.2) (n = 396) and remained
stable up to 24 months (P = 0.828). Compared with preoperative ECD, mean
postoperative ECD decreased by 37 (+/-18)%, 40 (+/-18)%, and 45 (+/-18)% at 6,
12, and 24 months, respectively (P < 0.05 for all time points). Surgery
indication and graft attachment status were related to postoperative BCVA and ECD
results. Eyes with FECD and attached grafts showed better BCVA outcomes and
higher ECD (P < 0.05). Central corneal thickness decreased by 20 (+/-11)% to 525
(+/-46) MUm from preoperative to 6 months postoperatively and remained stable
thereafter (P > 0.05). Within the study period, retransplantation was required in
32 eyes (6.4%). Principal longer-term complications were secondary graft failure
(1.4%) and allograft rejection (1.4%). CONCLUSIONS: Clinical outcomes remain
excellent up to 2 years after DMEK, in particular for eyes operated on for FECD
and with completely attached grafts.
PMID- 28410549
TI - Evaluation of Factors Influencing Antibody Reduction for Development of Antibody
Drug Conjugates
AB - Background: Reduction/alkylation is one of the leading strategies for the
development of antibody drug conjugates (ADCs). Precise control of the reduction
process would not only yield a defined number of free thiols per antibody but
also result in development of more homogenous conjugates. Methods: In the present
study, we investigated the effect of various dithiothreitol (DTT) concentrations,
temperature conditions, and DTT exposure times on antibody reduction. After
antibody reduction, the Ellman's test and SDS-PAGE analysis were used to evaluate
free thiols produced and confirm the reduction process, respectively. Results:
DTT concentration seems to be a potential factor in the reduction process.
Concentrations of 0.1, 1, 5, 10, 20, 50, and 100 mM DTT at 37 degrees C for 30
minutes resulted in approximately 0.4, 1.2, 5.4, 7, 8, 8, and 8 thiols per
antibody, respectively. Conclusion: Optimized site-specific conjugation can
provide better process control and reproducibility for the development of
disulfide-based ADCs.
PMID- 28410550
TI - Electrical and Photoelectrical Properties of Reduced Graphene Oxide-Porous
Silicon Nanostructures.
AB - In this work, the hybrid structures were created by electrochemical etching of
silicon wafer and deposition of reduced graphene oxide (RGO) on the porous
silicon (PS) layer. With the help of SEM and AFM, the formation of hybrid PS-RGO
structure was confirmed. By means of current-voltage characteristic analysis and
impedance spectroscopy, we studied electrical characteristics of PS-RGO
structures. The formation of photosensitive electrical barriers in hybrid
structures was revealed. Temporal parameters and spectral characteristics of
photoresponse in the 400-1100-nm wavelength range were investigated. The widening
of spectral range of photosensitivity of the hybrid structures in short
wavelength range in comparison with single-crystal silicon was revealed. The
obtained results broaden the prospects of application of the PS-RGO structures in
photoelectronics.
PMID- 28410551
TI - The Computational Studies of Plasmon Interaction.
AB - In this paper, an interaction of metal nanoparticles that appears in the
extinction spectra was investigated. The mutual coupling between the
nanoparticles, the effect of size difference, and the interparticle separation in
silver nanoparticle dimers are studied by computer discrete dipole approximation
methods. The obtained results show that nanoparticle interaction results in the
distinct collective modes, known as the low-energy bonding modes and the higher
energy antibounding modes. The spectral position of the modes is analyzed as a
function of the ratio of interparticle distance to particle size that reduces the
dependency on the particle size itself. The optical spectra of nanoparticles that
form the fractal cluster were investigated. It was found that the number of
spectral bands increase with the growth of the number of nanoparticles in the
fractal cluster, which are described within the plasmon hybridization model.
PMID- 28410552
TI - A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer
Therapy.
AB - Many anti-cancer drugs have a common problem of poor solubility. Increasing the
solubility of the drugs is very important for its clinical applications. In the
present study, we revealed that the solubility of insoluble drugs was
significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated
that RUB could form micelles, which was well characterized by Langmuir monolayer
investigation, transmission electron microscopy, atomic-force microscopy, and
cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with
the horizontal distance of ~25 nm and vertical distance of ~1.2 nm. Insoluble
synergistic anti-cancer drugs including curcumin and resveratrol were loaded in
RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR +
RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR
micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could
load other two insoluble drugs together for remarkably enhanced anti-cancer
effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded
that RUB-based micelles could efficiently load insoluble drugs for enhanced anti
cancer effect.
PMID- 28410553
TI - Effects of Photochromic Furan-Based Diarylethenes on Gold Nanoparticles
Aggregation.
AB - The photochromic properties of furan-based diarylethenes and their interaction
with citrate-capped gold nanoparticles were investigated by ultraviolet/visible
absorption spectroscopy and transmission electron microscopy. We identified the
optimal concentration of diarylethenes in water-ethanol mixture required for
stability of colloidal systems. Nanoparticles coupled with diarylethene
derivatives exhibit a new surface plasmon resonance band coming from their
aggregation. We analyzed the effects of functional side-chain groups on
aggregation process. These results can be considered as a basis for further
designing of novel hybrid nanomaterials and optoelectronic elements.
PMID- 28410554
TI - Yolk @ cage-Shell Hollow Mesoporous Monodispersion Nanospheres of Amorphous
Calcium Phosphate for Drug Delivery with High Loading Capacity.
AB - In this paper, yolk-shell hollow nanospheres of amorphous calcium phosphate (ACP)
are prepared, and its loading capacity is investigated by comparing with that of
solid-shell hollow structure ACP and cage-shell hollow structure ACP. Results
show that the products are yolk @ cage-shell of ACP with large shell's pores size
(15-40 nm) and large cavity volume. Adsorption results show that the loading
capacity of yolk @ cage-shell hollow spherical ACP is very high, which is more
than twice that of hollow ACP and 1.5 times of cage-like ACP. The main reasons
are that the big shell's pore size contributes the large molecular doxorubicin
hydrochloride (DOX . HCl) to enter the inner of hollow spheres easier, and the
yolk-shell structure provides larger interior space and more adsorption sites for
loading drugs.
PMID- 28410555
TI - Microwave Properties of One-dimensional Photonic Structures Based on Composite
Layers Filled with Nanocarbon.
AB - This work presents the results of computer modeling and experimental measurements
of microwave transmission properties for one-dimensional periodic multi-layered
photonic structures (PCs), composed of epoxy layers and composite layers filled
with nanocarbon particles-multi-walled carbon nanotubes and graphite
nanoplatelets. The results show that the characteristics of observed photonic
band gaps in transmission spectra of PC can be controlled by varying the
parameters of layers, namely, the complex permittivity and the layer thickness.
It was found that the insertion of the defects (for instance, magnetic layer)
into photonic structure can change the EMR transmission spectrum. The comparative
analysis of EMR transmission spectra for investigated photonic structures has
showed good agreement between the experimental and simulated data. It was found
that EMR absorption in composite layers of photonic structures shifts the
transmission spectra to the smaller values of EMR transmission index and reduces
the sharpness of photonic band gaps. Thus, by changing the parameters of
composite layers in photonic structure, we can obtain the tunable photonic band
gaps, necessary for technological applications in devices, capable of storing,
guiding, and filtering microwaves.
PMID- 28410556
TI - Electronic Structure and Charge-Trapping Characteristics of the Al2O3-TiAlO-SiO2
Gate Stack for Nonvolatile Memory Applications.
AB - In this work, high-k composite TiAlO film has been investigated as charge
trapping material for nonvolatile memory applications. The annealing formed Al2O3
TiAlO-SiO2 dielectric stack demonstrates significant memory effects and excellent
reliability properties. The memory device exhibits a large memory window of ~2.6
V under +/-8 V sweeping voltage, and it shows only ~14% charge loss after more
than 10 years' retention, indicating excellent charge retention properties. The
electronic structures of the Al2O3-TiAlO-SiO2 have been studied by X-ray
photoelectron spectroscopy measurements, and it reveals that the quantum well and
the defect traps in TiAlO film can provide a >1.8 eV deep barrier for charge
confinement in the TiAlO layer. The mixing between Al2O3 and TiO2 can increase
the defects related to the under-coordinated Ti3+ atoms, thereby enhancing the
charge-trapping efficiency of the device. Our work implies that high-k TiAlO
composite film is promising for applications in future nonvolatile charge
trapping memories.
PMID- 28410557
TI - Introducing Overlapping Grain Boundaries in Chemical Vapor Deposited Hexagonal
Boron Nitride Monolayer Films.
AB - We demonstrate the growth of overlapping grain boundaries in continuous,
polycrystalline hexagonal boron nitride (h-BN) monolayer films via scalable
catalytic chemical vapor deposition. Unlike the commonly reported atomically
stitched grain boundaries, these overlapping grain boundaries do not consist of
defect lines within the monolayer films but are composed of self-sealing bilayer
regions of limited width. We characterize this overlapping h-BN grain boundary
structure in detail by complementary (scanning) transmission electron microscopy
techniques and propose a catalytic growth mechanism linked to the subsurface/bulk
of the process catalyst and its boron and nitrogen solubilities. Our data suggest
that the overlapping grain boundaries are comparatively resilient against
deleterious pinhole formation associated with grain boundary defect lines and
thus may reduce detrimental breakdown effects when polycrystalline h-BN monolayer
films are used as ultrathin dielectrics, barrier layers, or separation membranes.
PMID- 28410558
TI - Ultrasensitive Vertical Piezotronic Transistor Based on ZnO Twin Nanoplatelet.
AB - High sensitivity of pressure/strain sensors is the key to accurately evaluating
external mechanical stimuli and could become more important in future generations
of human-machine interfaces and artificial skin. Here we report the study of a
two-terminal piezotronic transistor based on ZnO twin nanoplatelets (TNPT). Owing
to the mirror symmetrical structure of ZnO twin nanplatelet, compressive pressure
induced positive piezoelectric polarization charges created at both metal
semiconductor interfaces can simultaneously lower both Schottky barrier heights
and thus significantly modulate the carrier transport. Our device exhibits the
highest pressure sensitivity of 1448.08-1677.53 meV/MPa, which is more than ~20
times larger than the highest value reported previously, and a fast response time
of <5 ms. In addition, it can be used as a photodector with an ultrahigh external
photoresponsivity of ~1.45 * 104 AW-1, which is ~105 times larger in magnitude
than that of commercial UV photodetectors. The coupling between the mirror
symmetrical structure and strong piezotronic effect in ZnO twin nanoplatelets may
enable the development of ultrasensitive pressure/strain sensors for various
applications such as artificial skin, health monitoring, and adaptive biomedical
probes.
PMID- 28410560
TI - Role of Long-Acting Muscarinic Antagonist/Long-Acting beta2-Agonist Therapy in
Chronic Obstructive Pulmonary Disease.
AB - OBJECTIVE: To compare the available literature regarding the use of long-acting
muscarinic antagonist (LAMA)/long-acting beta2 agonists (LABA) and inhaled
corticosteroid (ICS)/LABA combination inhaler therapy in chronic obstructive
pulmonary disease (COPD) maintenance therapy management. DATA SOURCES: A MEDLINE
literature search from database inception to February 2017 was conducted using
the search terms chronic obstructive pulmonary disease, adrenergic beta-agonist,
muscarinic antagonist, and inhaled corticosteroid. References from extracted
sources were further searched for any relevant, missed data sources. STUDY
SELECTION AND DATA EXTRACTION: All English-language randomized-controlled trials
comparing LAMA/LABA and ICS/LABA combination inhaler therapy were evaluated. DATA
SYNTHESIS: A total of 10 randomized controlled trials have reviewed the use of
LAMA/LABA compared with ICS/LABA therapy for COPD maintenance therapy. Results of
clinical trials that evaluated LAMA/LABA and ICS/LABA maintenance therapy
demonstrated superior improvements in pulmonary function tests via spirometry and
improved clinical outcomes with LAMA/LABA therapy, specifically reduction in COPD
exacerbation rates. The safety of LAMA/LABA combination therapy also is favorable
compared with ICS/LABA combination therapy because of the increased infection
risk with ICS therapy. CONCLUSIONS: COPD is a disease state with significant
morbidity and mortality in the United States and is the third leading cause of
death. Long-acting inhalers are recommended for the majority of COPD severities,
and combination therapy is typically utilized. LAMA/LABA combination therapy has
demonstrated superior improvements in pulmonary function and reduction in COPD
exacerbation rates compared with ICS/LABA. LAMA/LABA combination therapy will
have a larger future role in COPD maintenance management.
PMID- 28410561
TI - Sexual dimorphism of the planum temporale in schizophrenia: A MRI study.
AB - OBJECTIVE: Anatomical alterations in the superior temporal gyrus have been
consistently reported in patients with schizophrenia, and they have mostly been
linked to positive symptoms, including hallucinations and thought disorders. The
superior temporal gyrus is considered one of the most asymmetric and lateralized
structure of the human brain, and the process of lateralization seems to vary
according to gender in the normal population. However, although it has been
consistently suggested that patients with schizophrenia did not show normal brain
lateralization in several regions, only few studies investigated it in the
superior temporal gyrus and its sub-regions considering the effects of gender. In
this context, the aim of this study was to evaluate sexual dimorphism in superior
temporal gyrus volumes in a sample of patients with schizophrenia compared to age
and gender-matched healthy controls. METHODS: A total of 72 right/left-handed
males (40 schizophrenia patients and 32 healthy controls) and 45 right/left
handed females (18 schizophrenia patients and 27 healthy controls) underwent
clinical evaluation and a 1.5T magnetic resonance imaging scan. Gray and white
matter volumes of regions of interest within the superior temporal gyrus were
manually detected, including the Heschl's gyrus and the planum temporale.
RESULTS: Female patients with schizophrenia presented a reduction in left planum
temporale gray matter volumes ( F = 4.58, p = 0.03) and a lack of the normal
planum temporale asymmetry index ( t = 0.27; p = 0.79) compared to female
controls ( t = 5.47; p = 0.001). No differences were found between males for any
volumes or laterality indices. Finally, in female patients with schizophrenia,
Heschl's gyrus gray and white matter volumes negatively correlated with positive
symptoms ( r = -0.56, p = 0.01). CONCLUSION: Our results showed that sexual
dimorphism plays a key role on planum temporale in schizophrenia, underlining the
importance of gender as a modulator of brain morphology and lateralization of
schizophrenia.
PMID- 28410559
TI - The "Iron"-y of Iron Overload and Iron Deficiency in Chronic Obstructive
Pulmonary Disease.
PMID- 28410562
TI - Superior vena cava reconstruction under the left internal jugular vein to left
femoral vein bypass support.
AB - The complete surgical resection of malignant thymoma is recommended. We present a
rare case of tumor resection and superior vena cava (SVC) reconstruction under
veno-venous bypass support from the left internal jugular vein to the left
femoral vein. The full amount of systemic heparinization (3 mg/kg) was avoided.
The surgical pathology revealed thymic squamous cell carcinoma. No complications
such as fatal extensive bleeding, coagulopathy, thromboembolism or transfusion
reaction were found postoperatively. The patient was discharged home
uneventfully. The support of this veno-venous bypass allows a safe and feasible
thymic tumor resection and SVC reconstruction.
PMID- 28410563
TI - Wernicke's encephalopathy following reduced food intake due to depressive
disorders.
AB - Wernicke's encephalopathy (WE) is an unexpected common neurological disorder
caused by thiamine deficiency often due to alcohol abuse, but WE-not alcohol
related is also frequent. A prolonged reduction of food intake can cause WE. This
condition can arise in depression disorders, especially in the early stages of
these psychiatric syndromes. WE is characterized by the triad of signs: ataxia,
ocular dysfunctions and confusional state. However, they rarely appear together
and this makes the diagnosis particularly difficult, especially when there is not
a history of alcohol abuse. Electroencephalography, since in the early stage of
the disease, can be helpful in detecting pattern of metabolic encephalopathy. We
describe three cases of thiamine deficiency responsible of WE, caused by a
decrease in appetite and food intake due to the onset of a depressive disorder.
In our series, the most frequent symptom observed at the onset of the disease was
the motor incoordination. We recommend to perform quickly thiamine infusion in
all depressed patients with a history of reduced food intake, presenting to
Emergency Department with recent onset of motor incoordination, with or without
alterations in eyes' movements and confusional state, after exclusion of other
neurological conditions.
PMID- 28410564
TI - A Review of Methods for Analysis of the Expected Value of Information.
AB - In recent years, value-of-information analysis has become more widespread in
health economic evaluations, specifically as a tool to guide further research and
perform probabilistic sensitivity analysis. This is partly due to methodological
advancements allowing for the fast computation of a typical summary known as the
expected value of partial perfect information (EVPPI). A recent review discussed
some approximation methods for calculating the EVPPI, but as the research has
been active over the intervening years, that review does not discuss some key
estimation methods. Therefore, this paper presents a comprehensive review of
these new methods. We begin by providing the technical details of these
computation methods. We then present two case studies in order to compare the
estimation performance of these new methods. We conclude that a method based on
nonparametric regression offers the best method for calculating the EVPPI in
terms of accuracy, computational time, and ease of implementation. This means
that the EVPPI can now be used practically in health economic evaluations,
especially as all the methods are developed in parallel with R functions and a
web app to aid practitioners.
PMID- 28410565
TI - Intensity of singular stress fields of wedge-shaped defect in human tooth due to
occlusal force before and after restoration with composite resins.
AB - Wedge-shaped defects are frequently observed on the cervical region of the human
tooth. Previously, most studies explained that improper tooth-brushing causes
such defects. However, recent clinical observation suggested that the repeated
stress due to occlusal force may induce the formation of these wedge-shaped
defects. In this study, therefore, two-dimensional human tooth models are
considered with and without a wedge-shaped defect by applying the finite element
method. To evaluate large stress concentrations accurately, a method of analysis
is discussed in terms of the intensity of singular stress fields appearing at the
tip of the sharp wedge-shaped defect. The effects of the position and direction
of occlusion on the intensity of singular stress fields are discussed before and
after restoration with composite resins.
PMID- 28410566
TI - Biomechanical effect of interspinous process distraction height after lumbar
fixation surgery: An in vitro model.
AB - Pedicle screw fixation may induce abnormal activity at adjacent segment and
accelerate the degeneration of lumbar vertebrae. Dynamic stabilizers could
provide an intermediate solution between conservative treatment and fusion
surgery. Lumbar vertebral segment cephalad to instrumented fixation was the most
common localization of adjacent segment degeneration. The aim of this study is to
explore the use of interspinous process devices in the lumbar vertebral segment
cephalad to fixation segment in changing the mechanical distribution and limiting
abnormal activity of the spine. Eight specimens were tested in the following
groups: intact group, instability group (bilateral facetectomy at L3-L4),
fixation group (bilateral facetectomy and pedicle screw fixation at L3-L4), and
hybrid fixation group (fixation at L3-L4 and simulating interspinous device
implantation of 6, 8, 10, 12, 14, 16, and 18 mm at L2-L3). Range of motion,
motion of vertebral body, and strain distribution change were recorded. The range
of motion in extension with 16- and 18-mm hybrid constructs was significantly
lower than intact, instability, and fixation groups. In flexion and lateral
bending, the strain values of L4 inferior articular process with 18-mm hybrid
construct have a significant difference compared with other groups. In axial
rotation, under the condition of a contralateral state, the strain values of L2
superior articular process with 18-mm hybrid construct have a significant
difference compared with intact and fixation groups. The strain value of the L4
inferior articular process had negative correlation with height distraction in
three dimensions, except extension. A negative correlation between the strain
value of the L2 superior articular process and distraction height was found in
contralateral bending and contralateral axial rotation. Interspinous process
devices above the fixation segment can change the mechanical distribution of the
spine and limit activity in some of the segments of the spine, which may delay
the degeneration of the adjacent segment.
PMID- 28410567
TI - Farm suicides in New Zealand, 2007-2015: A review of coroners' records.
AB - OBJECTIVE: Economic recessions and severe weather events are often associated
with increased suicide rates. The Global Dairy Crisis 2015/2016 led to an
economic downturn in the New Zealand dairy farming industry and, coupled with
droughts in some regions and floods in others, raised fears about increased
suicide rates among farmers. However, little was known about suicides in the
farming sector. This study reviews characteristics of recent farm-related
suicides in New Zealand and assesses the extent to which financial stresses
contributed to the deaths. METHODS: Data were abstracted from coroners' records
for a consecutive series of 185 people in farm- and agriculture-related
occupations who died by suicide between 2007 and 2015 and for whom coronial
inquiries had been completed. RESULTS: Farm suicides were heterogeneous: six
distinct risk profiles were identified. Financial stresses made negligible
contributions to farm suicides. Overall, risk factors for farm suicides differed
little from risk factors for suicide in the general population. However, suicide
risk in farmers was exacerbated by ready access to firearms: almost 40% of farm
suicides involved firearms, compared to 8% in the general population over the
same time. Among farm suicides, young male farm labourers predominated, rather
than farm owners or managers. For many young men, relationship losses, acute
alcohol intoxication and ready access to a firearm formed a common constellation
of risk factors. CONCLUSIONS: While coroners' records are variable and do not
record specific information about financial stresses and weather events, it was
clear that these issues made a negligible contribution to farm suicides. A range
of rural suicide prevention initiatives are needed to address various farm
suicide risk profiles. In particular, young male labourers often had no contact
with health services prior to death, suggesting that rural suicide prevention
efforts need to be positioned within community, farming and sports organisations,
as well as health and social service providers.
PMID- 28410568
TI - Health, functional ability and life satisfaction among older people 65 years and
over: a cross-sectional study.
AB - BACKGROUND: Satisfaction with life is a complex interplay of older people's
perspectives on life achievements. Satisfaction with life, alongside health and
functional ability contribute to successful ageing. AIM: To explore the impact of
increasing age on older people's perceptions of their health, functional ability
and life satisfaction. METHODS: A cross-sectional survey of non-institutionalised
older people (65+) was conducted (n = 542). The Short Form-12 Health Survey
measured perceived physical and mental health, the Groningen Activity Restriction
Scale measured functional ability and the Satisfaction With Life Scale measured
life satisfaction. RESULTS: Significant group differences were found; while
participants' perceptions of health and function decreased with age, perceptions
of life satisfaction increased. Unexpectedly, the youngest groups reported low
levels of life satisfaction while the oldest reported very high levels.
CONCLUSIONS: Further study should consider factors that might influence the
perception of health, functional ability and particularly life satisfaction
across older age groups.
PMID- 28410569
TI - Phenotypes of Rapid Cystic Fibrosis Lung Disease Progression during Adolescence
and Young Adulthood.
AB - RATIONALE: Individuals with cystic fibrosis are at risk for prolonged drops in
lung function, clinically termed rapid decline, during discreet periods of the
disease. OBJECTIVES: To identify phenotypes of rapid pulmonary decline and
determine how these phenotypes are related to patient characteristics. METHODS: A
longitudinal cohort study of patients with cystic fibrosis aged 6-21 years was
conducted using the Cystic Fibrosis Foundation Patient Registry. A statistical
approach for clustering longitudinal profiles, sparse functional principal
components analysis, was used to classify patients into distinct phenotypes by
evaluating trajectories of FEV1 decline. Phenotypes were compared with respect to
baseline and mortality characteristics. MEASUREMENTS AND MAIN RESULTS: Three
distinct phenotypes of rapid decline were identified, corresponding to early,
middle, and late timing of maximal FEV1 loss, in the overall cohort (n = 18,387).
The majority of variation (first functional principal component, 94%) among
patient profiles was characterized by differences in mean longitudinal FEV1
trajectories. Average degree of rapid decline was similar among phenotypes
(roughly -3% predicted/yr); however, average timing differed, with early, middle,
and late phenotypes experiencing rapid decline at 12.9, 16.3, and 18.5 years of
age, respectively. Individuals with the late phenotype had the highest initial
FEV1 but experienced the greatest loss of lung function. The early phenotype was
more likely to have respiratory infections and acute exacerbations at baseline or
to develop them subsequently, compared with other phenotypes. CONCLUSIONS: By
identifying phenotypes and associated risk factors, timing of interventions may
be more precisely targeted for subgroups at highest risk of lung function loss.
PMID- 28410570
TI - Natural selection drove metabolic specialization of the chromatophore in
Paulinella chromatophora.
AB - BACKGROUND: Genome degradation of host-restricted mutualistic endosymbionts has
been attributed to inactivating mutations and genetic drift while genes coding
for host-relevant functions are conserved by purifying selection. Unlike their
free-living relatives, the metabolism of mutualistic endosymbionts and
endosymbiont-originated organelles is specialized in the production of
metabolites which are released to the host. This specialization suggests that
natural selection crafted these metabolic adaptations. In this work, we analyzed
the evolution of the metabolism of the chromatophore of Paulinella chromatophora
by in silico modeling. We asked whether genome reduction is driven by metabolic
engineering strategies resulted from the interaction with the host. As its widely
known, the loss of enzyme coding genes leads to metabolic network restructuring
sometimes improving the production rates. In this case, the production rate of
reduced-carbon in the metabolism of the chromatophore. RESULTS: We reconstructed
the metabolic networks of the chromatophore of P. chromatophora CCAC 0185 and a
close free-living relative, the cyanobacterium Synechococcus sp. WH 5701. We
found that the evolution of free-living to host-restricted lifestyle rendered a
fragile metabolic network where >80% of genes in the chromatophore are essential
for metabolic functionality. Despite the lack of experimental information, the
metabolic reconstruction of the chromatophore suggests that the host provides
several metabolites to the endosymbiont. By using these metabolites as
intracellular conditions, in silico simulations of genome evolution by gene lose
recover with 77% accuracy the actual metabolic gene content of the chromatophore.
Also, the metabolic model of the chromatophore allowed us to predict by flux
balance analysis a maximum rate of reduced-carbon released by the endosymbiont to
the host. By inspecting the central metabolism of the chromatophore and the free
living cyanobacteria we found that by improvements in the gluconeogenic pathway
the metabolism of the endosymbiont uses more efficiently the carbon source for
reduced-carbon production. In addition, our in silico simulations of the
evolutionary process leading to the reduced metabolic network of the
chromatophore showed that the predicted rate of released reduced-carbon is
obtained in less than 5% of the times under a process guided by random gene
deletion and genetic drift. We interpret previous findings as evidence that
natural selection at holobiont level shaped the rate at which reduced-carbon is
exported to the host. Finally, our model also predicts that the ABC phosphate
transporter (pstSACB) which is conserved in the genome of the chromatophore of P.
chromatophora strain CCAC 0185 is a necessary component to release reduced-carbon
molecules to the host. CONCLUSION: Our evolutionary analysis suggests that in the
case of Paulinella chromatophora natural selection at the holobiont level played
a prominent role in shaping the metabolic specialization of the chromatophore. We
propose that natural selection acted as a "metabolic engineer" by favoring
metabolic restructurings that led to an increased release of reduced-carbon to
the host.
PMID- 28410572
TI - Incidence of infection following internal fixation of open and closed tibia
fractures in India (INFINITI): a multi-centre observational cohort study.
AB - BACKGROUND: Trauma is a major public health problem, particularly in India due to
the country's rapid urbanization. Tibia fractures are a common and often
complicated injury that is at risk of infection following surgical fixation. The
primary objectives of this cohort study were to determine the incidence of
infection within one year of surgery and to describe the distribution of
infections by location and time of diagnosis for tibia fractures in India.
METHODS: We conducted a multi-center, prospective cohort study. Patients who
presented with an open or closed tibia fracture treated with internal fixation to
one of the participating hospitals in India were invited to participate in the
study. Participants attended follow-up visits at 3, 6, and 12 months post
surgery, where they were assessed for infections, fracture healing, and health
related quality of life as measured by the EurQol-5 Dimensions (EQ-5D). RESULTS:
Seven hundred eighty-seven participants were included in the study and 768
participants completed the 12 month follow-up. The overall incidence of infection
was 2.9% (23 infections). The incidence of infection was 1.6% (10 infections) in
closed and 8.0% (13 infections) in open fractures. There were 7 deep and 16
superficial infections, with 5 being early, 7 being delayed, and 11 being late
infections. Intra-operative antibiotics were given to 92.1% of participants and
post-operative antibiotics were given to 96.8% of participants. Antibiotics were
prescribed for an average of 8.3 days for closed fractures and 9.1 days for open
fractures. Infected fractures took significantly longer to heal, and participants
who had an infection had significantly lower EQ-5D scores. CONCLUSIONS: The
incidence of infection within this cohort is similar to those seen in developed
countries. The duration of prophylactic antibiotic use was longer than standard
practice in North America, raising concern for the potential development of
antibiotic resistant microbes within Indian orthopaedic settings. Future research
should aim to identify the best practice for antibiotic use in India to ensure
that antibiotic usage patterns do not lead to unnecessary overuse, while
maintaining a low incidence of infection. TRIAL REGISTRATION: NCT01691599 ,
September 17, 2012.
PMID- 28410571
TI - Pre- and post-surgical evaluation of the inflammatory response in patients with
aortic stenosis treated with different types of prosthesis.
AB - BACKGROUND: The inflammatory process in aortic valvular stenosis persists after
surgery to replace the valve in almost half of the patients. No association has
been found to its persistence. The main objective of this study was to evaluate
the inflammatory response in patients with aortic stenosis through the
determination of several biomarkers in plasma measured before and after the
valvular replacement and to seek an association with the type of prosthesis used.
METHODS: This is an observational study with a follow up of 6 months in subjects
with severe aortic stenosis. Seric concentrations of TNFa, IL-1, IL-6 and ICAM
and echocardiographic variables were quantified previous to the surgery and a
week and 6 months after it. A group of control subjects paired by age and gender
was included. RESULTS: Seventy-nine subjects were studied of which 57% were male;
the average age was of 59 (+/- 11.4) years. Previous to surgery, the
concentration of cytokines was higher in patients than in control subjects. A
biological prosthesis was implanted in 48 patients and a mechanical prosthesis in
31. Both, types of prosthesis have components made of titanium. The
echocardiograms 1 week and 6 months after the surgery showed a decrease in the
mean aortic gradient and an increase in the valvular area (p = 0.001). Half of
the patients still showed high proinflammatory cytokine levels. There were no
differences according to the type of prosthesis implanted after adjustments for
demographic variables, comorbidities and echocardiographic data. CONCLUSIONS: The
inflammatory response caused by both types of valvular prothesis at 6 months
after implantation were similar. Both types of prosthesis are recommended, they
had similarities in hemodynamic profiles registered with Doppler
echocardiography. Age of the patient or the suitability use of anticoagulants
determines the type of prosthesis to be used.
PMID- 28410573
TI - Risk factors for necrotizing enterocolitis in neonates: a systematic review of
prognostic studies.
AB - BACKGROUND: Necrotizing enterocolitis (NEC) is a severe multifactorial disease in
preterm neonates associated with high morbidity and mortality. Better insight
into prognostic values of the many reported factors associated with NEC is needed
to enable identification of neonates at risk for NEC. The aim was to
systematically review the literature to identify independent risk factors for NEC
from the literature. METHODS: Medline, Cochrane, Embase, Pubmed and Google
Scholar were searched systematically for cohort studies reporting prognostic
factors for NEC in neonates using multivariable analysis. Studies were scored
with the Quality In Prognosis Studies tool (QUIPS). RESULTS: From 5154 initial
hits, 14 prognostic studies were included, with various designs. Study quality
was rated high in three studies, moderate or low in the 11 others. Significant
prognostic factors for NEC reported in at least two studies were: low birth
weight, small for gestational age, low gestational age, assisted ventilation,
premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension
(all increased risk), surfactant therapy (conflicting results) and cesarean
section (lower risk). Meta-analysis was considered not feasible. CONCLUSION: High
quality studies on prognostic factors for NEC are rare. Several prognostic
factors, that are not necessarily causal, are associated with NEC. High quality
prognostic research is necessary to establish the predictive values of these
factors.
PMID- 28410574
TI - Comparison of different cell type correction methods for genome-scale epigenetics
studies.
AB - BACKGROUND: Whole blood is frequently utilized in genome-wide association studies
of DNA methylation patterns in relation to environmental exposures or clinical
outcomes. These associations can be confounded by cellular heterogeneity.
Algorithms have been developed to measure or adjust for this heterogeneity, and
some have been compared in the literature. However, with new methods available,
it is unknown whether the findings will be consistent, if not which method(s)
perform better. RESULTS: Methods: We compared eight cell-type correction methods
including the method in the minfi R package, the method by Houseman et al., the
Removing unwanted variation (RUV) approach, the methods in FaST-LMM-EWASher,
ReFACTor, RefFreeEWAS, and RefFreeCellMix R programs, along with one approach
utilizing surrogate variables (SVAs). We first evaluated the association of DNA
methylation at each CpG across the whole genome with prenatal arsenic exposure
levels and with cancer status, adjusted for estimated cell-type information
obtained from different methods. We then compared CpGs showing statistical
significance from different approaches. For the methods implemented in minfi and
proposed by Houseman et al., we utilized homogeneous data with composition of
some blood cells available and compared them with the estimated cell
compositions. Finally, for methods not explicitly estimating cell compositions,
we evaluated their performance using simulated DNA methylation data with a set of
latent variables representing "cell types". RESULTS: Results from the SVA-based
method overall showed the highest agreement with all other methods except for
FaST-LMM-EWASher. Using homogeneous data, minfi provided better estimations on
cell types compared to the originally proposed method by Houseman et al. Further
simulation studies on methods free of reference data revealed that SVA provided
good sensitivities and specificities, RefFreeCellMix in general produced high
sensitivities but specificities tended to be low when confounding is present, and
FaST-LMM-EWASher gave the lowest sensitivity but highest specificity.
CONCLUSIONS: Results from real data and simulations indicated that SVA is
recommended when the focus is on the identification of informative CpGs. When
appropriate reference data are available, the method implemented in the minfi
package is recommended. However, if no such reference data are available or if
the focus is not on estimating cell proportions, the SVA method is suggested.
PMID- 28410575
TI - Effects of omega-3 fatty acids on patients undergoing surgery for
gastrointestinal malignancy: a systematic review and meta-analysis.
AB - BACKGROUND: Surgical resection remains the primary treatment for gastrointestinal
(GI) malignancy including early-stage cancer. Omega-3 polyunsaturated fatty acids
(n-3 PUFAs) have been reported to have beneficial clinical and immune-modulating
effects in the prognosis of GI cancer patients undergoing surgery. METHODS: We
searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled
Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the
effects of n-3 PUFAs compared with isocaloric nutrition on GI cancer patients who
underwent surgery up to the end of June 30, 2016. Two authors independently
reviewed and selected eligible randomized controlled trials (RCTs). RESULTS: A
total of 9 RCTs (623 participants) were included. The n-3 PUFAs regime resulted
in lower levels of C-reactive protein (CRP) (P < 0.05), interleukin-6 (IL-6) (P <
0.01), and higher levels of albumin (ALB), CD3+ T cells, CD4+ T cells and
CD4+/CD8+ ratio (P < 0.05) compared with the isocaloric nutrition regime.
However, there was no significant difference in the level of tumor necrosis
factor-alpha (TNF-alpha) between the n-3 PUFAs regime and the isocaloric
nutrition regime (P = 0.17). And the level of CD8 + T cells decreased compared
with the isocaloric nutrition regime (P < 0.0001). CONCLUSIONS: Our meta-analysis
revealed that n-3 PUFAs are effective in improving the nutritional status and
immune function of GI cancer patients undergoing surgery as they effectively
enhance immunity and attenuate the inflammatory response.
PMID- 28410576
TI - Knowledge and attitude regarding pharmacogenetics among formerly pregnant women
in the Netherlands and their interest in pharmacogenetic research.
AB - BACKGROUND: Pharmacogenetics is an emerging field currently being implemented to
improve safety when prescribing drugs. While many women who take drugs during
pregnancy would likely benefit from such personalized drug therapy, data is
lacking on the awareness towards pharmacogenetics among women. We aim to
determine the level of knowledge and acceptance of formerly pregnant women in the
Netherlands regarding pharmacogenetics and its implementation, and their interest
in pharmacogenetic research. METHODS: A population-based survey using postal
questionnaires was conducted among formerly pregnant women in the Northern parts
of the Netherlands. A total of 986 women were invited to participate. RESULTS: Of
the 219 women who returned completed questionnaires (22.2% response rate), only
22.8% had heard of pharmacogenetics, although the majority understood the concept
(64.8%). Women who had experience with drug side-effects were more likely to know
about pharmacogenetics [OR = 2.06, 95% CI 1.16, 3.65]. Of the respondents, 53.9%
were positive towards implementing pharmacogenetics in their future drug therapy,
while 46.6% would be willing to participate in pharmacogenetic research. Among
those who were either not willing or undecided in this regard, their concerns
were about the consequences of the pharmacogenetic test, including the privacy
and anonymity of their genetic information. CONCLUSION: The knowledge and
attitude regarding the concept of pharmacogenetics among our population of
interest is good. Also, their interest in pharmacogenetic research provides
opportunities for future research related to drug use during pregnancy and fetal
outcome.
PMID- 28410577
TI - A candidate RxLR effector from Plasmopara viticola can elicit immune responses in
Nicotiana benthamiana.
AB - BACKGROUND: Diverse plant pathogens deliver effectors into plant cells to alter
host processes. Oomycete pathogen encodes a large number of putative RxLR
effectors which are likely to play a role in manipulating plant defense
responses. The secretome of Plasmopara viticola (downy mildew of grapevine)
contains at least 162 candidate RxLR effectors discovered in our recent studies,
but their roles in infection and pathogenicity remain to be determined. Here, we
characterize in depth one of the putative RxLR effectors, PvRxLR16, which has
been reported to induce cell death in Nicotiana benthamiana in our previous
study. RESULTS: The nuclear localization, W/Y/L motifs, and a putative N
glycosylation site in C-terminal of PvRxLR16 were essential for cell death
inducing activity. Suppressor of G-two allele of Skp1 (SGT1), heat shock protein
90 (HSP90) and required for Mla12 resistance (RAR1), but not somatic
embryogenesis receptor-like kinase (SERK3), were required for the cell death
response triggered by PvRxLR16 in N. benthamiana. Some mitogen-activated protein
kinases and transcription factors were also involved in the perception of
PvRxLR16 by N. benthamiana. PvRxLR16 could also significantly enhance plant
resistance to Phytophthora capsici and the nuclear localization was required for
this ability. However, some other PvRxLR effectors could suppress defense
responses and disease resistance induced by PvRxLR16, suggesting that it may not
trigger host cell death or immune responses during physiological infection under
natural conditions. CONCLUSION: These data demonstrate that PvRxLR16 may be
recognized by endogenous proteins in nucleus to trigger immune responses in N.
benthamiana, which in turn can be suppressed by other PvRxLR effectors.
PMID- 28410578
TI - Serum low-density lipoprotein and low-density lipoprotein expression level at
diagnosis are favorable prognostic factors in patients with small-cell lung
cancer (SCLC).
AB - BACKGROUND: Patients with small-cell lung cancer (SCLC) patients demonstrate
varied survival outcomes. Previous studies have reported that lipoproteins are
associated with prognosis in various cancers; however, the role of low-density
lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients
with SCLC has not been studied. METHODS: In this study, the impact of LDL and
LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients
with SCLC were retrospectively evaluated, in which 198 patients had adequate
tissues for immunohistochemistry, and serum LDL and LDLR expression levels at
baseline were tested. X-tile tool, and univariate and multivariate Cox analysis
were used to assess the association between LDL, LDLR and overall survival (OS).
RESULTS: Univariate analysis demonstrated that a lower LDL level was
significantly associated with superior OS (P = 0.037). Similarly, LDLR also
significantly predicted OS (P = 0.003). Multivariate Cox analyses confirmed that
lower LDL and LDLR expression was independent prognostic factors associated with
longer OS (P = 0.019 and P = 0.027, respectively). CONCLUSIONS: This study showed
that both LDL and LDLR are prognostic indexes for survival in patients with SCLC.
Patients with high LDL or LDLR expression level may benefit from treatment that
modulates lipoprotein combined with platinum-based chemotherapy.
PMID- 28410579
TI - Assessing the usability by clinicians of VISION: A hierarchical display of
patient-collected physiological information to clinicians.
AB - BACKGROUND: The inability of patients to accurately and completely recount their
clinical status between clinic visits reduces the clinician's ability to properly
manage their patients. One way to improve this situation is to collect objective
patient information while the patients are at home and display the collected
multi-day clinical information in parallel on a single screen, highlighting
threshold violations for each channel, and allowing the viewer to drill down to
any analog signal on the same screen, while maintaining the overall physiological
context of the patient. All this would be accomplished in a way that was easy for
the clinician to view and use. METHODS: Patients used five mobile devices to
collect six heart failure-related clinical variables: body weight, systolic and
diastolic blood pressure, pulse rate, blood oxygen saturation, physical activity,
and subjective input. Fourteen clinicians practicing in a heart failure clinic
rated the display using the System Usability Scale that, for acceptability, had
an expected mean of 68 (SD, 12.5). In addition, we calculated the Intraclass
Correlation Coefficient of the clinician responses using a two-way, mixed effects
model, ICC (3,1). RESULTS: We developed a single-screen temporal hierarchical
display (VISION) that summarizes the patient's home monitoring activities between
clinic visits. The overall System Usability Scale score was 92 (95% CI, 87-97), p
< 0.0001; the ICC was 0.89 (CI, 0.79-0.97), p < 0.0001. CONCLUSION: Clinicians
consistently found VISION to be highly usable. To our knowledge, this is the
first single-screen, parallel variable, temporal hierarchical display of both
continuous and discrete information acquired by patients at home between clinic
visits that presents clinically significant information at the point of care in a
manner that is usable by clinicians.
PMID- 28410580
TI - Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal
response: an ex-vivo organ culture model of post-infectious irritable bowel
syndrome.
AB - BACKGROUND: The evidence on the role of gut microbiota in post-infectious
irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively
affect IBS symptoms, although the mechanisms through which probiotics exert their
beneficial effects are largely unknown. The aim of the study is to evaluate the
role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the
inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.
METHODS: Ex vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea
predominant subtype (D) patients, and 10 healthy controls (HC) were treated with
LPS, LC-DG and PB. Interleukin (IL)-1alpha, IL-6, IL-8 and IL-10 mRNA levels were
assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by
Western blotting. RESULTS: At baseline, IL-1alpha, IL-6 and IL-8 mRNA levels as
well as TLR-4 protein expression were significantly higher while IL-10 mRNA
levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB
significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4
while increased that of IL-10 after LPS stimulation. The protective effect was
more pronounced for PB than LC-DG treatment. CONCLUSION: LC-DG and its PB
attenuate the inflammatory mucosal response in an ex-vivo organ culture model of
PI-IBS D.
PMID- 28410581
TI - Statistical evaluation of adding multiple risk factors improves Framingham stroke
risk score.
AB - BACKGROUND: Framingham Stroke Risk Score (FSRS) is the most well-regarded risk
appraisal tools for evaluating an individual's absolute risk on stroke onset.
However, several widely accepted risk factors for stroke were not included in the
original Framingham model. This study proposed a new model which combines an
existing risk models with new risk factors using synthesis analysis, and applied
it to the longitudinal Atherosclerosis Risk in Communities (ARIC) data set.
METHODS: Risk factors in original prediction models and new risk factors in
proposed model had been discussed. Three measures, like discrimination,
calibration and reclassification, were used to evaluate the performance of the
original Framingham model and new risk prediction model. RESULTS: Modified C
statistics, Hosmer-Lemeshow Test and classless NRI, class NRI were the
statistical indices which, respectively, denoted the performance of
discrimination, calibration and reclassification for evaluating the newly
developed risk prediction model on stroke onset. It showed that the NEW-STROKE
(new stroke risk score prediction model) model had higher modified C-statistics,
smaller Hosmer-Lemeshow chi-square values after recalibration than original FSRS
model, and the classless NRI and class NRI of the NEW-STROKE model over the
original FSRS model were all significantly positive in overall group. CONCLUSION:
The NEW-STROKE integrated with seven literature-derived risk factors outperformed
the original FSRS model in predicting the risk score of stroke. It illustrated
that seven literature-derived risk factors contributed significantly to stroke
risk prediction.
PMID- 28410582
TI - Metronidazole for the treatment of Tritrichomonas foetus in bulls.
AB - BACKGROUND: Tritrichomonas foetus is a sexually transmitted protozoon that causes
reproductive failure, among cattle, so disruptive that many western US states
have initiated control programs. Current control programs are based on the
testing and exclusion of individual bulls. Unfortunately, these programs are
utilizing screening tests that are lacking in sensitivity. Blanket treatment of
all the exposed bulls and adequate sexual rest for the exposed cows could provide
a more viable disease control option. The objectives of this study were twofold.
The first objective was to demonstrate effectiveness for metronidazole treatment
of a bull under ideal conditions and with an optimized treatment regime. This
type of study with a single subject is often referred to as an n-of-1 or single
subject clinical trial. The second objective of the current study was to review
the scientific basis for the banning of metronidazole for use in Food Animals by
the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). RESULTS:
Results from an antimicrobial assay indicated that metronidazole at a
concentration of 0.5 MUg/mL successfully eliminated in vitro protozoal growth of
bovine Tritrichomonas foetus. The estimated effective intravenous dose was two
treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested
positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior
to treatment was negative for Tritrichomonas foetus culture at weekly intervals
for five consecutive weeks following this treatment regimen. An objective
evaluation of the published evidence on the potential public health significance
of using metronidazole to treat Tritrichomonas foetus in bulls provides
encouragement for veterinarians and regulators to consider approaches that might
lead to permitting the legal use of metronidazole in bulls. CONCLUSION: The study
demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in
vivo with metronidazole. The current status of metronidazole is that the Animal
Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in
food-producing animals. Veterinarians and regulators should consider approaches
that might lead to permitting the legal use of metronidazole in bulls.
PMID- 28410583
TI - Short-term motor learning through non-immersive virtual reality task in
individuals with down syndrome.
AB - BACKGROUND: Down syndrome (DS) has unique physical, motor and cognitive
characteristics. Despite cognitive and motor difficulties, there is a possibility
of intervention based on the knowledge of motor learning. However, it is
important to study the motor learning process in individuals with DS during a
virtual reality task to justify the use of virtual reality to organize
intervention programs. The aim of this study was to analyze the motor learning
process in individuals with DS during a virtual reality task. METHODS: A total of
40 individuals participated in this study, 20 of whom had DS (24 males and 8
females, mean age of 19 years, ranging between 14 and 30 yrs.) and 20 typically
developing individuals (TD) who were matched by age and gender to the individuals
with DS. To examine this issue, we used software that uses 3D images and
reproduced a coincidence-timing task. RESULTS: The results showed that all
individuals improved performance in the virtual task, but the individuals with DS
that started the task with worse performance showed higher difference from the
beginning. Besides that, they were able to retain and transfer the performance
with increase of speed of the task. CONCLUSION: Individuals with DS are able to
learn movements from virtual tasks, even though the movement time was higher
compared to the TD individuals. The results showed that individuals with DS who
started with low performance improved coincidence- timing task with virtual
objects, but were less accurate than typically developing individuals. TRIAL
REGISTRATION: ClinicalTrials.gov Identifier: NCT02719600 .
PMID- 28410584
TI - Case-crossover study to examine the change in postpartum risk of pulmonary
embolism over time.
AB - BACKGROUND: Although the current guidelines recommend anticoagulation up until 6
weeks after delivery in women at high risk of venous thromboembolism (VTE), the
risk of VTE may extend beyond 6 weeks. Our objective was to estimate the risk of
a pulmonary embolism in successive 2-week intervals during the postpartum period.
METHODS: In a population-based, case-crossover study, we analyzed the French
national inpatient database from 2007 to 2013 (n = 5,517,680 singleton
deliveries). Using ICD-10 codes, we identified women who were diagnosed with a
postpartum pulmonary embolism between July 1st, 2008, and December 31st, 2013.
Deliveries were identified during a case "period" immediately before the
pulmonary embolism, and five different control periods one year before the
pulmonary embolism. Using conditional logistic regression, Odds ratios (ORs) and
95% confidential intervals (CIs) were estimated for ten successive 2-week
intervals that preceded the diagnosis of pulmonary embolism. RESULTS: We
identified 167,103 cases with a pulmonary embolism during the inclusion period.
After delivery, the risk of pulmonary embolism declined progressively over time,
with an OR [95%CI] of 17.2 [14.0-21.3] in postpartum weeks 1 to 2 and 1.9 [1.4
2.7] in postpartum weeks 11 to 12. The OR [95%CI] in postpartum weeks 13 to 14
was 1.4 [0.9-2.0], and the OR did not fall significantly after postpartum week
14. CONCLUSIONS: Our findings indicate that women are at risk of a pulmonary
embolism up to 12 weeks after delivery. The shape of the risk curve suggests that
the risk decreases exponentially over time. Future research is needed to
establish whether the duration of postpartum anticoagulation should be extended
beyond 6 weeks.
PMID- 28410585
TI - Practical application of opt-out recruitment methods in two health services
research studies.
AB - BACKGROUND: Participant recruitment is an ongoing challenge in health research.
Recruitment may be especially difficult for studies of access to health care
because, even among those who are in care, people using services least often also
may be hardest to contact and recruit. Opt-out recruitment methods (in which
potential participants are given the opportunity to decline further contact about
the study (opt out) following an initial mailing, and are then contacted directly
if they have not opted out within a specified period) can be used for such
studies. However, there is a dearth of literature on the effort needed for
effective opt-out recruitment. METHODS: In this paper we describe opt-out
recruitment procedures for two studies on access to health care within the U.S.
Department of Veterans Affairs. We report resource requirements for recruitment
efforts (number of opt-out packets mailed and number of phone calls made). We
also compare the characteristics of study participants to potential participants
via t-tests, Fisher's exact tests, and chi-squared tests. RESULTS: Recruitment
rates for our two studies were 12 and 21%, respectively. Across multiple study
sites, we had to send between 4.3 and 9.2 opt-out packets to recruit one
participant. The number of phone calls required to arrive at a final status for
each potentially eligible Veteran (i.e. study participation or the termination of
recruitment efforts) were 2.9 and 6.1 in the two studies, respectively. Study
participants differed as expected from the population of potentially eligible
Veterans based on planned oversampling of certain subpopulations. The final
samples of participants did not differ statistically from those who were mailed
opt-out packets, with one exception: in one of our two studies, participants had
higher rates of mental health service use in the past year than did those mailed
opt-out packets (64 vs. 47%). CONCLUSIONS: Our results emphasize the practicality
of using opt-out methods for studies of access to health care. Despite the
benefits of these methods, opt-out alone may be insufficient to eliminate non
response bias on key variables. Researchers will need to balance considerations
of sample representativeness and feasibility when designing studies investigating
access to care.
PMID- 28410586
TI - Efficacy and safety of Jianzhong decoction in treating peptic ulcers: a meta
analysis of 58 randomised controlled trials with 5192 patients.
AB - BACKGROUND: Jianzhong decoction is widely used to treat peptic ulcers; however,
due to lack of systematic evaluations, its clinical efficacy remains
controversial. We performed meta-analysis to evaluate the efficacy and safety of
Jianzhong decoction in treating peptic ulcers. METHODS: Studies were
systematically retrieved from PubMed, Embase, Cochrane library, China National
Knowledge Infrastructure, Wanfang Database, Chongqing VIP, China Biology Medicine
disc (CBMdisc), and references cited in related studies/reviews. Extracted data
included the total effective rate, helicobacter pylori eradication rates,
recurrence rate, and adverse reaction rate. Fifty-eight randomised controlled
trials involving 5192 patients were included in the final analysis. RESULTS:
Results showed that Jianzhong decoction therapy was more effective than
conventional Western medicine therapy (total effective rate, odds ratio [OR] =
4.29, 95% confidence interval [CI]: 3.51-5.23, P = 0.000; helicobacter pylori
eradication rates, OR =2.10, 95% CI: 1.69-2.61, P = 0.000; recurrence rate, OR
=0.23, 95% CI: 0.18-0.29, P = 0.000; and adverse reaction rate, OR =0.20, 95% CI:
0.12-0.33, P = 0.000). CONCLUSIONS: Jianzhong decoction increased the total
effective rate and helicobacter pylori eradication rate, and lowered the
recurrence and adverse reaction rates. The results of this study can be used as a
guide for clinical treatment of peptic ulcers.
PMID- 28410587
TI - Overview of cancer incidence and mortality among people living with HIV/AIDS in
British Columbia, Canada: Implications for HAART use and NADM development.
AB - BACKGROUND: The objective of this study is to evaluate the incidence of non-AIDS
defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in
British Columbia, focusing on clinical correlates, highly active antiretroviral
therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM
development. METHODS: A retrospective population based analysis was carried out
for individuals with HIV/AIDS that began their treatment between 1996 and 2008.
RESULTS: There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies
(ADMs) identified in 4918 PLWHA in the study population. NADMs were represented
by a range of cancer types including, most commonly, lung cancer, followed by
anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a
SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals
without an HIV/AIDS diagnosis in the general population. Independent factors
significantly associated with a NADM were: male gender, older age, lower CD4 cell
counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment
during the early-HAART era (before 2000 versus after 2000). CONCLUSIONS: NADMs
represent an important source of morbidity for PLWHA. Use of HAART with its
associated improvement in immune-restoration, and tailored targeted cancer
screening interventions, may be beneficial and improve outcomes in this unique
patient population.
PMID- 28410588
TI - Evidence synthesis to inform model-based cost-effectiveness evaluations of
diagnostic tests: a methodological review of health technology assessments.
AB - BACKGROUND: Evaluations of diagnostic tests are challenging because of the
indirect nature of their impact on patient outcomes. Model-based health economic
evaluations of tests allow different types of evidence from various sources to be
incorporated and enable cost-effectiveness estimates to be made beyond the
duration of available study data. To parameterize a health-economic model fully,
all the ways a test impacts on patient health must be quantified, including but
not limited to diagnostic test accuracy. METHODS: We assessed all UK NIHR HTA
reports published May 2009-July 2015. Reports were included if they evaluated a
diagnostic test, included a model-based health economic evaluation and included a
systematic review and meta-analysis of test accuracy. From each eligible report
we extracted information on the following topics: 1) what evidence aside from
test accuracy was searched for and synthesised, 2) which methods were used to
synthesise test accuracy evidence and how did the results inform the economic
model, 3) how/whether threshold effects were explored, 4) how the potential
dependency between multiple tests in a pathway was accounted for, and 5) for
evaluations of tests targeted at the primary care setting, how evidence from
differing healthcare settings was incorporated. RESULTS: The bivariate or HSROC
model was implemented in 20/22 reports that met all inclusion criteria. Test
accuracy data for health economic modelling was obtained from meta-analyses
completely in four reports, partially in fourteen reports and not at all in four
reports. Only 2/7 reports that used a quantitative test gave clear threshold
recommendations. All 22 reports explored the effect of uncertainty in accuracy
parameters but most of those that used multiple tests did not allow for
dependence between test results. 7/22 tests were potentially suitable for primary
care but the majority found limited evidence on test accuracy in primary care
settings. CONCLUSIONS: The uptake of appropriate meta-analysis methods for
synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in
recent years. Future research should focus on other evidence requirements for
cost-effectiveness assessment, threshold effects for quantitative tests and the
impact of multiple diagnostic tests.
PMID- 28410589
TI - Lung involvement in childhood onset granulomatosis with polyangiitis.
AB - Granulomatosis with polyangiitis is an ANCA-associated systemic vasculitis with a
low incidence in the pediatric population. Lung involvement is a common
manifestation in children affected by granulomatosis with polyangiitis, both at
disease's onset and during flares. Its severity is variable, ranging from
asymptomatic pulmonary lesions to dramatic life-threatening clinical
presentations such as diffuse alveolar haemorrhage. Several radiologic findings
have been described, but the most frequent abnormalities detected are nodular
lesions and fixed infiltrates. Interstitial involvement, pleural disease and
pulmonary embolism are less common. Histology may show necrotizing or
granulomatous vasculitis of small arteries and veins of the lung, but since
typical features may be patchy, the site for lung biopsy should be carefully
chosen with the help of imaging techniques such as computed tomography.
Bronchoalveolar lavage is helpful to confirm the diagnosis of alveolar
haemorrhage. Pulmonary function tests are frequently altered, showing a reduction
in the diffusion capacity for carbon monoxide, which can be associated with
obstructive abnormalities related to airway stenosis. Nodular lung lesions tend
to regress with immunosuppressive therapy, but lung disease may also require
second line treatments such as plasmapheresis. In cases of massive diffuse
alveolar haemorrhage, ventilator support is crucial in the management of the
patient.
PMID- 28410590
TI - Early predictors of poor outcome after out-of-hospital cardiac arrest.
AB - BACKGROUND: Early identification of predictors for a poor long-term outcome in
patients who survive the initial phase of out-of-hospital cardiac arrest (OHCA)
may facilitate future clinical research, the process of care and information
provided to relatives. The aim of this study was to determine the association
between variables available from the patient's history and status at intensive
care admission with outcome in unconscious survivors of OHCA. METHODS: Using the
cohort of the Target Temperature Management trial, we performed a post hoc
analysis of 933 unconscious patients with OHCA of presumed cardiac cause who had
a complete 6-month follow-up. Outcomes were survival and neurological function as
defined by the Cerebral Performance Category (CPC) scale at 6 months after OHCA.
After multiple imputations to compensate for missing data, backward stepwise
multivariable logistic regression was applied to identify factors independently
predictive of a poor outcome (CPC 3-5). On the basis of these factors, a risk
score for poor outcome was constructed. RESULTS: We identified ten independent
predictors of a poor outcome: older age, cardiac arrest occurring at home,
initial rhythm other than ventricular fibrillation/tachycardia, longer duration
of no flow, longer duration of low flow, administration of adrenaline, bilateral
absence of corneal and pupillary reflexes, Glasgow Coma Scale motor response 1,
lower pH and a partial pressure of carbon dioxide in arterial blood value lower
than 4.5 kPa at hospital admission. A risk score based on the impact of each of
these variables in the model yielded a median (range) AUC of 0.842 (0.840-0.845)
and good calibration. Internal validation of the score using bootstrapping
yielded a median (range) AUC corrected for optimism of 0.818 (0.816-0.821).
CONCLUSIONS: Among variables available at admission to intensive care, we
identified ten independent predictors of a poor outcome at 6 months for initial
survivors of OHCA. They reflected pre-hospital circumstances (six variables) and
patient status on hospital admission (four variables). By using a simple and easy
to-use risk scoring system based on these variables, patients at high risk for a
poor outcome after OHCA may be identified early.
PMID- 28410591
TI - Eurasian golden jackal as host of canine vector-borne protists.
AB - BACKGROUND: Jackals are medium-sized canids from the wolf-like clade, exhibiting
a unique combination of ancestral morphotypes, broad trophic niches, and close
phylogenetic relationships with the wolf and dog. Thus, they represent a
potential host of several pathogens with diverse transmission routes. Recently,
populations of the Eurasian golden jackal Canis aureus have expanded into the
Western Palaearctic, including most of Europe. The aim of our study was to
examine Eurasian golden jackals from Romania, Czech Republic and Austria for a
wide spectrum of vector-borne protists and to evaluate the role of this species
as a reservoir of disease for domestic dogs and/or humans. RESULTS: Diagnostic
polymerase chain reaction (PCR) DNA amplifications revealed 70% of jackals to be
positive for Hepatozoon, 12.5% positive for piroplasms, and one individual
positive for Leishmania infantum. Phylogenetic analyses of partial 18S rDNA
sequences invariably placed sequenced isolates of Hepatozoon into the H. canis
clade. For piroplasms, both the 18S and cox1 sequences obtained confirmed the
presence of Babesia canis and "Theileria annae" in 5 and 2 individuals,
respectively, providing the first records of these two piroplasmids in Eurasian
golden jackals. A single animal from Dolj County (Romania) was PCR-positive for
L. infantum, as confirmed also by sequencing of ITS1-5.8S. CONCLUSIONS:
Apparently, expanding populations of jackals can play a significant role in
spreading and maintaining new Babesia canis foci in Central Europe. The role of
jackals in the epidemiology of "Theileria annae" and H. canis is probably similar
to that of red foxes and should be taken into account in further research on
these parasites. Also the presence of L. infantum deserves attention. Our study
confirms that once established, the populations of Eurasian golden jackals
constitute natural reservoirs for many canine vector-borne diseases, analogous to
the role of the coyotes in North America.
PMID- 28410592
TI - Study of SV40 large T antigen nucleotide specificity for DNA unwinding.
AB - BACKGROUND: Simian Virus 40 (SV40) Large Tumor Antigen (LT) is an essential
enzyme that plays a vital role in viral DNA replication in mammalian cells. As a
replicative helicase and initiator, LT assembles as a double-hexamer at the SV40
origin to initiate genomic replication. In this process, LT converts the chemical
energy from ATP binding and hydrolysis into the mechanical work required for
unwinding replication forks. It has been demonstrated that even though LT
primarily utilizes ATP to unwind DNA, other NTPs can also support low DNA
helicase activity. Despite previous studies on specific LT residues involved in
ATP hydrolysis, no systematic study has been done to elucidate the residues
participating in the selective usage of different nucleotides by LT. In this
study, we performed a systematic mutational analysis around the nucleotide pocket
and identified residues regulating the specificity for ATP, TTP and UTP in LT DNA
unwinding. METHODS: We performed site-directed mutagenesis to generate 16 LT
nucleotide pocket mutants and characterized each mutant's ability to unwind
double-stranded DNA, oligomerize, and bind different nucleotides using helicase
assays, size-exclusion chromatography, and isothermal titration calorimetry,
respectively. RESULTS: We identified four residues in the nucleotide pocket of
LT, cS430, tK419, cW393 and cL557 that selectively displayed more profound impact
on using certain nucleotides for LT DNA helicase activity. CONCLUSION: Little is
known regarding the mechanisms of nucleotide specificity in SV40 LT DNA unwinding
despite the abundance of information available for understanding LT nucleotide
hydrolysis. The systematic residue analysis performed in this report provides
significant insight into the selective usage of different nucleotides in LT
helicase activity, increasing our understanding of how LT may structurally prefer
different energy sources for its various targeted cellular activities.
PMID- 28410593
TI - Comparing health-related quality of life of Dutch and Chinese patients with
traumatic brain injury: do cultural differences play a role?
AB - BACKGROUND: There is growing interest in health related quality of life (HRQoL)
as an outcome measure in international trials. However, there might be
differences in the conceptualization of HRQoL across different socio-cultural
groups. The objectives of current study were: (I) to compare HRQoL, measured with
the short form (SF)-36 of Dutch and Chinese traumatic brain injury (TBI) patients
1 year after injury and; (II) to assess whether differences in SF-36 profiles
could be explained by cultural differences in HRQoL conceptualization. TBI
patients are of particular interest because this is an important cause of diverse
impairments and disabilities in functional, physical, emotional, cognitive, and
social domains that may drastically reduce HRQoL. METHODS: A prospective cohort
study on adult TBI patients in the Netherlands (RUBICS) and a retrospective
cohort study in China were used to compare HRQoL 1 year post-injury. Differences
on subscales were assessed with the Mann-Whitney U-test. The internal
consistency, interscale correlations, item-internal consistency and item
discriminate validity of Dutch and Chinese SF-36 profiles were examined.
Confirmatory factor analysis was performed to assess whether Dutch and Chinese
data fitted the SF-36 two factor-model (physical and mental construct). RESULTS:
Four hundred forty seven Dutch and 173 Chinese TBI patients were included. Dutch
patients obtained significantly higher scores on role limitations due to
emotional problems (p < .001) and general health (p < .001), while Chinese
patients obtained significantly higher scores on physical functioning (p < .001)
and bodily pain (p = .001). Scores on these subscales were not explained by
cultural differences in conceptualization, since item- and scale statistics were
all sufficient. However, differences among Dutch and Chinese patients were found
in the conceptualization of the domains vitality, mental health and social
functioning. CONCLUSIONS: One year after TBI, Dutch and Chinese patients reported
a different pattern of HRQoL. Further, there might be cultural differences in the
conceptualization of some of the SF-36 subscales, which has implications for
outcome evaluation in multi-national trials.
PMID- 28410594
TI - Physical human-robot interaction of an active pelvis orthosis: toward ergonomic
assessment of wearable robots.
AB - BACKGROUND: In human-centered robotics, exoskeletons are becoming relevant for
addressing needs in the healthcare and industrial domains. Owing to their close
interaction with the user, the safety and ergonomics of these systems are
critical design features that require systematic evaluation methodologies. Proper
transfer of mechanical power requires optimal tuning of the kinematic coupling
between the robotic and anatomical joint rotation axes. We present the methods
and results of an experimental evaluation of the physical interaction with an
active pelvis orthosis (APO). This device was designed to effectively assist in
hip flexion-extension during locomotion with a minimum impact on the
physiological human kinematics, owing to a set of passive degrees of freedom for
self-alignment of the human and robotic hip flexion-extension axes. METHODS: Five
healthy volunteers walked on a treadmill at different speeds without and with the
APO under different levels of assistance. The user-APO physical interaction was
evaluated in terms of: (i) the deviation of human lower-limb joint kinematics
when wearing the APO with respect to the physiological behavior (i.e., without
the APO); (ii) relative displacements between the APO orthotic shells and the
corresponding body segments; and (iii) the discrepancy between the kinematics of
the APO and the wearer's hip joints. RESULTS: The results show: (i) negligible
interference of the APO in human kinematics under all the experimented
conditions; (ii) small (i.e., < 1 cm) relative displacements between the APO
cuffs and the corresponding body segments (called stability); and (iii)
significant increment in the human-robot kinematics discrepancy at the hip
flexion-extension joint associated with speed and assistance level increase.
CONCLUSIONS: APO mechanics and actuation have negligible interference in human
locomotion. Human kinematics was not affected by the APO under all tested
conditions. In addition, under all tested conditions, there was no relevant
relative displacement between the orthotic cuffs and the corresponding anatomical
segments. Hence, the physical human-robot coupling is reliable. These facts prove
that the adopted mechanical design of passive degrees of freedom allows an
effective human-robot kinematic coupling. We believe that this analysis may be
useful for the definition of evaluation metrics for the ergonomics assessment of
wearable robots.
PMID- 28410595
TI - Examining the role of macrolides and host immunity in combatting filarial
parasites.
AB - Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are
known for their effectiveness against a broad spectrum of disease-causing
nematodes and arthropods in humans and animals. In most nematodes, drugs in this
class induce paralysis, resulting in starvation, impaired ability to remain
associated with their anatomical environment, and death of all life stages.
Initially, this was also thought to be the ML mode of action against filarial
nematodes, but researchers have not been able to validate these characteristic
effects of immobilization/starvation of MLs in vitro, even at higher doses than
are possible in vivo. Relatively recently, ML receptor sites exclusively located
proximate to the excretory-secretory (ES) apparatus were identified in Brugia
malayi microfilaria and an ML-induced suppression of secretory protein release by
B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that
suppression of these ES proteins prevents the filarial worm from interfering with
the host's complement cascade, reducing the ability of the parasite to evade the
immune system. Live microfilariae and/or larvae, thus exposed, are attacked and
presented to the host's innate immune mechanisms and are ultimately killed by the
immune response, not the ML drug. These live, exposed filarial worms stimulate
development of innate, cellular and humoral immune responses that when properly
stimulated, are capable of clearing all larvae or microfilariae present in the
host, regardless of their individual sensitivity to MLs. Additional research in
this area can be expected to improve our understanding of the relationships among
filarial worms, MLs, and the host immune system, which likely would have
implications in filarial disease management in humans and animals.
PMID- 28410596
TI - Toll-like receptor 4 in glial inflammatory responses to air pollution in vitro
and in vivo.
AB - BACKGROUND: Exposure to traffic-related air pollution (TRAP) is associated with
accelerated cognitive aging and higher dementia risk in human populations. Rodent
brains respond to TRAP with activation of astrocytes and microglia, increased
inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4
(TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung
macrophage responses to air pollution. METHODS: To further analyze these
mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA
responses to nanoscale particulate matter (nPM; diameter <0.2 MUm), a well
characterized nanoscale particulate matter subfraction of TRAP collected from a
local freeway (Morgan et al. Environ Health Perspect 2011; 119,1003-1009, 2011).
The nPM was compared with responses to the endotoxin lipopolysaccharide (LPS), a
classic TLR4 ligand, using Affymetrix whole genome microarray in rats. Expression
patterns were analyzed by significance analysis of microarrays (SAM) for fold
change and by weighted gene co-expression network analysis (WGCNA) to identify
modules of shared responses between nPM and LPS. Finally, we examined TLR4
activation in hippocampal tissue from mice chronically exposed to nPM. RESULTS:
SAM and WGCNA analyses showed strong activation of TLR4 and NF-kappaB by both nPM
and LPS. TLR4 siRNA attenuated TNFalpha and other inflammatory responses to nPM
in vitro, via the MyD88-dependent pathway. In vivo, mice chronically exposed to
nPM showed increased TLR4, MyD88, TNFalpha, and TNFR2 RNA, and decreased NF
kappaB and TRAF6 RNA TLR4 and NF-kappaB responses in the hippocampus.
CONCLUSIONS: These results show TLR4 activation is integral in brain inflammatory
responses to air pollution, and warrant further study of TLR4 in accelerated
cognitive aging by air pollution.
PMID- 28410597
TI - The role of nuclear localization signal in parvovirus life cycle.
AB - Parvoviruses are small, non-enveloped viruses with an approximately 5.0 kb,
single-stranded DNA genome. Usually, the parvovirus capsid gene contains one or
more nuclear localization signals (NLSs), which are required for guiding the
virus particle into the nucleus through the nuclear pore. However, several
classical NLSs (cNLSs) and non-classical NLSs (ncNLSs) have been identified in
non-structural genes, and the ncNLSs can also target non-structural proteins into
the nucleus. In this review, we have summarized recent research findings on
parvovirus NLSs. The capsid protein of the adeno-associated virus has four
potential nuclear localization sequences, named basic region 1 (BR), BR2, BR3 and
BR4. BR3 was identified as an NLS by fusing it with green fluorescent protein.
Moreover, BR3 and BR4 are required for infectivity and virion assembly. In
Protoparvovirus, the canine parvovirus has a common cNLS located in the VP1
unique region, similar to parvovirus minute virus of mice (MVM) and porcine
parvovirus. Moreover, an ncNLS is found in the C-terminal region of MVM VP1/2.
Parvovirus B19 also contains an ncNLS in the C-terminal region of VP1/2, which is
essential for the nuclear transport of VP1/VP2. Approximately 1 or 2 cNLSs and 1
ncNLS have been reported in the non-structural protein of bocaviruses.
Understanding the role of the NLS in the process of parvovirus infection and its
mechanism of nuclear transport will contribute to the development of therapeutic
vaccines and novel antiviral medicines.
PMID- 28410598
TI - Prevalence of overweight and obesity among police officers in Riyadh City and
risk factors for cardiovascular disease.
AB - BACKGROUND: Despite the prevalence of overweight and obesity and increases in
associated diseases such as diabetes and heart disease in the Saudi population,
no studies have addressed the spread of obesity among Saudi police officers.
Therefore, the present study aimed to assess the prevalence of overweight and
obesity and associations with biochemical parameters among the police in Riyadh.
METHOD: The study involved a cross-sectional survey of 160 police officers in
Riyadh, Saudi Arabia. Anthropometric measurements, blood pressure, lipid profiles
and fasting blood sugar levels were measured for all individuals. RESULTS:
According to the results, the average body mass index (BMI) was 27.5 +/- 5.1,
indicating an increase in overweight in this population and 66.9% were overweight
or obese. Moreover, the mean systolic and diastolic blood pressure values were
119.5 and 79.4 mmHg, respectively, within normal limits. The mean total
cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density
lipoprotein-cholesterol (LDL-C), and triglyceride (TG) levels were 187.5, 43.9,
119.5 and 124.5 mg/100 ml, respectively. DISCUSSION: These BMI and biochemical
findings suggest a high proportion of overweight and obese individuals in the
sample population, as well as an increase in the proportion of individuals with
high levels of biochemical indicators who are therefore susceptible to heart
disease and diabetes. CONCLUSION: The study recommends using preventive programs
to combat obesity and overweight and related diseases and conducting further
studies using measures other than BMI.
PMID- 28410600
TI - Primary adrenal non-Hodgkin lymphoma: a case report and review of the literature.
AB - BACKGROUND: Lymphomas are cancers that arise from the white blood cells and have
been traditionally divided into two large subtypes: Hodgkin and non-Hodgkin
lymphoma. B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma;
almost 85% of patients with lymphoma have this variant. Lymphomas can potentially
arise from any lymphoid tissue located in the body; however, primary adrenal non
Hodgkin lymphoma is extremely rare. We report the history, examination findings,
and laboratory results of a 50-year-old man diagnosed with a primary left adrenal
diffuse large B-cell lymphoma. CASE PRESENTATION: A 50-year-old Pakistani man
presented to our hospital with progressively increasing pain and fullness in the
left upper quadrant of his abdomen, generalized weakness, easy fatigability, and
decreased appetite of 1.5 months' duration. On examination, he had a blood
pressure of 140/80 mmHg with no postural drop, a pulse rate of 106 beats/minute,
and no fever. His past medical history was significant for pulmonary tuberculosis
2 years earlier, for which he received antituberculous therapy. Computed
tomography revealed a heterogeneous enhancing soft tissue density mass in the
left adrenal gland. It measured 7.1 * 5.6 * 9.5 cm. Further laboratory workup
revealed the following levels: sodium 135 mEq/L, potassium 4.5 mEq/L, lactate
dehydrogenase 905 IU/L, renin 364 IU/ml, aldosterone 5.79 ng/dl,
dehydroepiandrosterone sulfate 79.20 MUg/dl, urinary vanillylmandelic acid 6.4
mg/24 hours, and a low-dose overnight dexamethasone suppression test result of
3.20 MUg/dl. The patient underwent left adrenalectomy. Histopathological test
results showed a diffuse large B-cell lymphoma. Immunohistochemical stains were
strongly positive for CD20 and negative for CD3, CD5, CD10, and cyclin D1. The
patient's Ki-67 (Mib-1) index was approximately 80%. He received a total of six
cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy
(rituximab was not given, owing to financial constraints) and was routinely
followed pre- and postchemotherapy at our hematology clinic with complete blood
count and serum lactate dehydrogenase evaluations. The patient responded to
chemotherapy and is currently doing well. CONCLUSIONS: Primary adrenal lymphoma
is an extremely rare but rapidly progressive disease. It generally carries a poor
prognosis, partly because an optimal treatment protocol has not yet been
established. Further studies with larger sample sizes are needed to establish the
best treatment option and increase overall survival.
PMID- 28410599
TI - The role of vitamin C in the treatment of pain: new insights.
AB - The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain
and recent epidemiological evidence has indicated an association between
suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence
indicates that vitamin C administration can exhibit analgesic properties in some
clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency
is high in various patient groups, such as surgical/trauma, infectious diseases
and cancer patients. A number of recent clinical studies have shown that vitamin
C administration to patients with chronic regional pain syndrome decreases their
symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high
dose vitamin C administration. Furthermore, cancer-related pain is decreased with
high dose vitamin C, contributing to enhanced patient quality of life. A number
of mechanisms have been proposed for vitamin C's analgesic properties. Herein we
propose a novel analgesic mechanism for vitamin C; as a cofactor for the
biosynthesis of amidated opioid peptides. It is well established that vitamin C
participates in the amidation of peptides, through acting as a cofactor for
peptidyl-glycine alpha-amidating monooxygenase, the only enzyme known to amidate
the carboxy terminal residue of neuropeptides and peptide hormones. Support for
our proposed mechanism comes from studies which show a decreased requirement for
opioid analgesics in surgical and cancer patients administered high dose vitamin
C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for
acute and chronic pain relief in specific patient groups.
PMID- 28410601
TI - The diagnosis and management of NK/T-cell lymphomas.
AB - Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignancy of
putative NK-cell origin, with a minority deriving from the T-cell lineage.
Pathologically, the malignancy occurs in two forms, extranodal NK/T-cell
lymphoma, nasal type; and aggressive NK-cell leukaemia. Lymphoma occur most
commonly (80%) in the nose and upper aerodigestive tract, less commonly (20%) in
non-nasal areas (skin, gastrointestinal tract, testis, salivary gland), and
rarely as disseminated disease with a leukemic phase. Genetic analysis showed
mutations of genes involved in the JAK/STAT pathway, RNA assembly, epigenetic
regulation, and tumor suppression. In initial clinical evaluation, positron
emission tomography computed tomography, and quantification of plasma EBV DNA are
mandatory as they are useful for response monitoring and prognostication. In
stage I/II diseases, combined chemotherapy and radiotherapy (sequentially or
concurrently) is the best approach. Conventional anthracycline-containing
regimens are ineffective and should be replaced by non-anthracycline-containing
regimens, preferably including L-asparaginase. Radiotherapy alone is associated
with high systemic relapse rates and should be avoided. In stage III/IV diseases,
non-anthracycline-regimens-containing L-asparaginase are the standard. In
relapsed/refractory cases, blockade of the programmed death protein 1 has
recently shown promising results with high response rates. In the era of
effective non-anthracycline-containing regimens, autologous haematopoietic stem
cell transplantation (HSCT) has not been shown to be beneficial. However,
allogeneic HSCT may be considered for high-risk or advanced-stage patients in
remission or relapsed/refractory patients responding to salvage therapy.
Prognostic models taking into account presentation, interim, and end-of-treatment
parameters are useful in triaging patients to different treatment strategies.
PMID- 28410602
TI - Extreme caution on the use of sirolimus for the congenital hyperinsulinism in
infancy patient.
AB - We have recently published on the limited effectiveness of sirolimus as a
treatment option for hypoglycaemia as a consequence of hyperinsulinism. Our data
oppose the view that mTOR inhibitors provide new opportunities for the treatment
of patients with hyperinsulinism. We are not convinced by the argument that any
benefit for some patients outweighs the potential and later long-term problems
that accompany mTOR inhibition in the neonate. We also express the opinion that
caution must be taken when repurposing/repositioning therapies in the field of
rare disease.
PMID- 28410603
TI - Unexpected episodes of cyanosis in late preterm and term neonates prompted
admission to a neonatal care unit.
AB - BACKGROUND: We studied late preterm and term infants who were admitted to our
neonatal care unit in a tertiary hospital for unexpected episodes of cyanosis
that occurred during rooming-in for evaluation of their frequency, most frequent
associated diseases, and documentation of the diagnostic clinical approach.
METHODS: We carried out a retrospective study of infants with a gestational age
>=35 weeks who were admitted from the nursery with the diagnosis of cyanosis from
January 2009 to December 2016. Exclusion criteria were the occurrence of
acrocyanosis and the diagnosis of sudden unexpected postnatal collapse (SUPC).
RESULTS: We studied 49 infants with a mean gestational age of 38 +/- 2 weeks. The
frequency of admission for cyanosis was 1.8/1000 live births and was similar (p =
0.167) in late preterm and term infants. The majority of episodes occurred during
the first 24 h of life (57%). Only 16 infants (33%) were discharged with a
diagnosis, that was mostly (n = 5;10%) gastro-esophageal reflux. CONCLUSIONS:
Unexpected episodes of cyanosis caused admission of 1.8/1000 live births to the
neonatal care unit without differences between late preterm and term infants.
These episodes occurred mainly during the first day of life and infants were
mostly discharged without a known diagnosis.
PMID- 28410604
TI - The association of patient and trauma characteristics with the health-related
quality of life in a Dutch trauma population.
AB - BACKGROUND: It is suggested in literature to use the Health Related Quality of
Life (HRQoL) as an outcome indicator for evaluating trauma centre performances.
In order to predict HRQoL, characteristics that could be of influence on a
predictive model should be identified. This study identifies patient and injury
characteristics associated with the HRQoL in a general trauma population.
METHODS: Retrospective study of trauma patients admitted from 1st January 2007
through 31th December 2012. Patients were aged >=18 years and discharged alive
from the level I trauma centre. A combined health survey (SF-36 and EQ-5D) was
sent to all traceable patients. The subdomain outcomes and EQ-5D index value (EQ
5Di) were compared with the reference population. A linear regression analysis
was performed to identify parameters associated parameters with the HRQoL
outcome. RESULTS: A total of 1870 patients were included for analyses. Compared
to the eligible population, included patients were significantly older, more
severely injured, more often admitted in the ICU and had a longer admission
duration. The SF-36 and EQ-5Di were significantly lower compared to the Dutch
reference population. The variables age, Injury Severity Score, hospital length
of stay, ICU length of stay, Revised Trauma Score, probability of survival, and
severe injury to the head and extremities were associated with the HRQoL in the
majority of the subdomains. DISCUSSION: In order to use HRQoL as an indicator for
trauma centre performances, there should be a consensus of the ideal timing for
the measurement of HRQoL post-injury and the appropriate HRQoL instrument.
Furthermore, standardised HRQoL outcomes must be developed. CONCLUSION: This
study revealed eight factors (described above) which could be used to predict the
HRQoL in trauma patients.
PMID- 28410605
TI - Frosted branch angiitis and cerebral venous sinus thrombosis as an initial onset
of neuro-Behcet's disease: a case report and review of the literature.
AB - BACKGROUND: Frosted branch angiitis is a rare, severe condition. It can be either
a primary or a secondary condition and is characterized by rapid deterioration of
vision and fulminant retinal vasculitis that manifests as diffuse sheathing of
retinal vessels, macular edema, papillitis, vitritis and anterior uveitis. We
aimed to describe a case of frosted branch angiitis and cerebral venous sinus
thrombosis as an initial neuro-Behcet's disease onset. Diagnosis of Behcet's
disease was based on the current 2014 International Criteria for Behcet's Disease
and the International consensus recommendation criteria for neuro-Behcet's
disease. In addition, a literature review using search parameters of "frosted
branch angiitis", "Behcet" and "neuro-Behcet" in the PubMed database is
presented. CASE PRESENTATION: A 28-year-old Brazilian pardo woman presented to
our hospital with abrupt bilateral vision loss associated with recurrent aphthous
oral ulcers 6 months before visual symptom onset. A fundus examination showed
bilateral widespread retinal vasculitis with venous and arterial white sheathing,
optic disc swelling, macular edema, and retinal hemorrhages, leading to the
diagnosis of frosted branch angiitis. An extensive systemic workup for retinal
vasculitis was uneventful, except for brain magnetic resonance imaging
demonstrating cerebral venous sinus thrombosis and lymphocytic aseptic
meningitis. A diagnosis of neuro-Behcet's disease was made, and treatment was
started with methylprednisolone therapy 1 g/day for 5 consecutive days, followed
by oral mycophenolate mofetil and infliximab 5 mg/kg infusion. The patient's
response was rapid, with improvement of visual acuity to hand movement and
counting fingers by day 7 and final visual acuity of counting fingers and 20/130.
CONCLUSIONS: Frosted branch angiitis may be associated with infectious,
noninfectious, or idiopathic causes. An extensive workup should be done to
exclude systemic vasculitis such as Behcet's disease. Treatment with systemic
steroids must be promptly initiated in association with specific treatment aimed
at inflammation control and blindness risk reduction.
PMID- 28410606
TI - In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice
following skin application post-ultraviolet radiation.
AB - BACKGROUND: Previous work has demonstrated size, surface charge and skin barrier
dependent penetration of nanoparticles into the viable layers of mouse skin. The
goal of this work was to characterize the tissue distribution and mechanism of
transport of nanoparticles beyond skin, with and without Ultraviolet Radiation
(UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow
cytometry and confocal microscopy were used to examine the effect of UVR dose
(180 and 360 mJ/cm2 UVB) on the skin penetration and systemic distribution of
quantum dot (QD) nanoparticles topically applied at different time-points post
UVR using a hairless C57BL/6 mouse model. RESULTS: Results indicate that QDs can
penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased
cadmium in the local lymph nodes of all QD treated mice. The average % recovery
for all treatment groups was 69.68% with ~66.84% of the applied dose recovered
from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the
applied dose was recovered from the lymph nodes across various treatment groups.
When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier
defect and LC migration to the local lymph node, there is an increased cellular
presence of QD in the lymph node; however, AAS analysis of local lymph nodes
display no difference in cadmium levels due to UVR treatment. CONCLUSIONS: Our
data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport
to the lymph node may occur by both cellular (dendritic and macrophage) and non
cellular mechanisms. It is interesting that these specific nanoparticles were
retained in skin similarly regardless of UVR barrier disruption, but the observed
skin immune cell interaction with nanoparticles suggest a potential for
immunomodulation, which we are currently examining in a murine model of skin
allergy.
PMID- 28410607
TI - ApreciseKUre: an approach of Precision Medicine in a Rare Disease.
AB - BACKGROUND: Alkaptonuria (AKU; OMIM:203500) is a classic Mendelian genetic
disorder described by Garrod already in 1902. It causes urine to turn black upon
exposure to air and also leads to ochronosis as well as early osteoarthritis. Our
objective is the implementation of a Precision Medicine (PM) approach to AKU. We
present here a novel ApreciseKUre database facilitating the collection,
integration and analysis of patient data in order to create an AKU-dedicated "PM
Ecosystem" in which genetic, biochemical and clinical resources can be shared
among registered researchers. In order to exploit the ApreciseKUre database, we
developed an analytic method based on Pearson's correlation coefficient and P
value that generates as refreshable correlation matrix. A complete statistical
analysis is obtained by associating every pair of parameters to examine the
dependence between multiple variables at the same time. SHORT CONCLUSIONS:
Employing this analytic approach, we showed that some clinically used biomarkers
are not suitable as prognostic biomarkers in AKU for a more reliable patients'
clinical monitoring. We believe this database could be a good starting point for
the creation of a new clinical management tool in AKU, which will lead to the
development of a deeper knowledge network on the disease and will advance its
treatment. Moreover, our approach can serve as a personalization model paradigm
for other inborn errors of metabolism or rare diseases in general.
PMID- 28410608
TI - Cross-sectional survey of selected enteric viruses in Polish turkey flocks
between 2008 and 2011.
AB - BACKGROUND: Enteric diseases are an important health problem for the intensive
poultry industry, resulting in considerable economic losses. Apart from such
microbiological agents associated with enteritis as bacteria and parasites, a lot
of research has been recently conducted on viral origin of enteric diseases.
However, enteric viruses have been identified in intestinal tract of not only
diseased but also healthy poultry, so their role in enteritis is still unclear.
The present study aimed at determination of the prevalence of four enteric
viruses, namely astrovirus, coronavirus, parvovirus and rotavirus in meat-type
turkey flocks in Poland as well as at statistical evaluation of the occurrence of
the studied viruses and their relationships with the health status and the age of
birds. Two hundred and seven flocks of birds aged 1-20 weeks originating from
different regions of the country were investigated between 2008 and 2011.
Clinical samples (10 individual faecal swabs/flock) were duly processed and
examined using molecular methods targeting the conservative regions of viral
genomes: RNA-dependent RNA polymerase gene of astrovirus, non-structural 1 gene
of parvovirus, non-structural protein 4 gene of rotavirus, and 5' untranslated
region fragment of turkey coronavirus. Different statistical methods (i.e. the
independence chi-square test, the correspondence analysis and the logistic
regression model) were used to establish any relationships between the analyzed
data. RESULTS: Overall, 137 (66.2%, 95% CI: 59.3-72.6) of the 207 turkey flocks
sampled were infected with one or more enteric viruses. Among the 137 flocks, 74
(54%, 95% CI: 45.3-62.6) were positive for one virus, whereas 54 (39.4%, 9 5% CI:
31.2-48.1) and 9 (6.6%, 95% CI: 3.1-12.1) were co-infected with two or three
different enteric viruses, respectively. No flock was simultaneously infected
with all four viruses studied. The prevalence of astrovirus infection was 44.9%
(95% CI: 38.0-52.0), parvovirus 27.5% (95% CI: 21.6-34.2), rotavirus 18.8% (95%
CI: 13.8-24.8), and coronavirus 9.7% (95% CI: 6.0-14.5). Young turkeys aged 1-4
weeks old had the highest (82.1%, 95% CI:71.7-89.8) prevalence of viral
infection. Applied statistical methods have indicated the dependence of rotavirus
infection as well as the co-infection with multiple viruses and the health status
of turkeys. Furthermore, our results statistically confirm that especially young
birds are susceptible to infection with rotavirus and astrovirus. CONCLUSIONS:
The study demonstrated the presence of astrovirus, coronavirus, parvovirus and
rotavirus infections in Polish turkey farms. These viruses were detected in both
healthy and diseased birds. However, the presented results provide valuable
feedback which could help to evaluate the role of some enteric viruses in the
etiology of enteritis in turkey.
PMID- 28410609
TI - Engineered microbial biosensors based on bacterial two-component systems as
synthetic biotechnology platforms in bioremediation and biorefinery.
AB - Two-component regulatory systems (TCRSs) mediate cellular response by coupling
sensing and regulatory mechanisms. TCRSs are comprised of a histidine kinase
(HK), which serves as a sensor, and a response regulator, which regulates
expression of the effector gene after being phosphorylated by HK. Using these
attributes, bacterial TCRSs can be engineered to design microbial systems for
different applications. This review focuses on the current advances in TCRS-based
biosensors and on the design of microbial systems for bioremediation and their
potential application in biorefinery.
PMID- 28410610
TI - An intricate case of multidrug resistant Plasmodium falciparum isolate imported
from Cambodia.
AB - BACKGROUND: Imported cases of multidrug resistant Plasmodium falciparum and
treatment failure with artemisinin-based regimens, although rare, have been
described also in Western countries and their management is often challenging.
This is also due to an inadequate knowledge and implementation of health
prevention measures. CASE REPORT: A complex case of imported malaria caused by
Plasmodium vivax/P. falciparum isolates in a patient who was not taking
chemoprophylaxis while he was travelling in Cambodia is reported in this article.
After failures of artemisinin-based and both oral and intravenous quinine-based
regimens, a multidrug resistant P. falciparum was detected. The patient was
successfully treated with atovaquone-proguanil. CONCLUSIONS: This experience
highlights the importance of a careful management that should be based not only
on the most up-to-date guidelines, but also on the awareness of a rapidly
evolving scenario.
PMID- 28410611
TI - Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical
excision and terbinafine treatment: a case report and review of the literature.
AB - BACKGROUND: Scedosporium apiospermum is an emerging opportunistic filamentous
fungus, which is notorious for its high levels of antifungal-resistance. It is
able to cause localized cutaneous or subcutaneous infections in both
immunocompromised and immunocompetent persons, pulmonary infections in patients
with predisposing pulmonary diseases and invasive mycoses in immunocompromised
patients. Subcutaneous infections caused by this fungus frequently show chronic
mycetomatous manifestation. CASE REPORT: We report the case of a 70-year-old
immunocompromised man, who developed a fungal mycetomatous infection on his right
leg. There was no history of trauma; the aetiological agent was identified by
microscopic examination and ITS sequencing. This is the second reported case of
S. apiospermum subcutaneous infections in Hungary, which was successfully treated
by surgical excision and terbinafine treatment. After 7 months, the patient
remained asymptomatic. Considering the antifungal susceptibility and increasing
incidence of the fungus, Scedosporium related subcutaneous infections reported in
the past quarter of century in European countries were also reviewed.
CONCLUSIONS: Corticosteroid treatment represents a serious risk factor of S.
apiospermum infections, especially if the patient get in touch with manure
enriched or polluted soil or water. Such infections have emerged several times in
European countries in the past decades. The presented data suggest that besides
the commonly applied voriconazole, terbinafine may be an alternative for the
therapy of mycetomatous Scedosporium infections.
PMID- 28410612
TI - Milk protein-based formulas containing different oils affect fatty acids balance
in term infants: A randomized blinded crossover clinical trial.
AB - BACKGROUND: Palm olein is used in infant formula fat blends in order to match the
fatty acid profile of human milk. While the effects on fatty acid balance have
been evaluated, the use of palm olein in combination with palm kernel oil and
supplementation with docosahexaenoic acid (DHA) and arachidonic acid (ARA) has
not been similarly assessed in infants. This study evaluated the effects of
infant formulas containing different fat compositions on the balance of fat,
fatty acids, and calcium. METHODS: In this randomized, crossover, double-blinded
study, 33 healthy term infants (68-159 +/- 3 days of age at enrollment) were fed
two formulas for 14 days in a tolerance period, followed by a 4-day metabolic
balance period in 17 of the male subjects. The study compared two commercially
available milk-based powdered formulas in Brazil; the PALM formula contained palm
olein (44%), kernel palm oil (21.7%), and canola oil (18.5%) as the predominant
fats, whereas the NoPALM formula contained other fat sources. RESULTS: Fat
absorption (%) was greater for NoPALM versus PALM-fed infants (96.55 and 95.50%,
respectively; p = 0.023). The absorption percentage of palmitic acid (C16:0) did
not differ significantly between formulas (p > 0.05), but this acid was excreted
at significantly higher concentrations in the PALM (29.42 mg/kg/day) than in the
NoPALM (12.28 mg/kg/day) formula groups. DHA and ARA absorption percentages were
also higher in NoPALM-fed infants. Calcium absorption was higher in NoPALM-fed
infants (58.00%) compared to those fed PALM (40.90%), but the difference was not
significant (p = 0.104) when calcium intake was used as a covariate. However,
calcium retention was higher in NoPALM-fed infants compared to that in PALM-fed
infants with or without calcium intake as a covariate. Adverse events did not
differ between groups (p > 0.05). CONCLUSIONS: The absorption of essential fatty
acids was similar for both formulas; however, long-chain polyunsaturated fatty
acids (DHA and ARA) were better absorbed from the NoPALM formula. Fat absorption
and calcium retention were lower in term infants fed the PALM-based formula.
CLINICAL TRIAL REGISTRATION: Clinicaltrial.gov # NCT00941564 .
PMID- 28410613
TI - Evaluation of six serological ELISA kits available in Italy as screening tests
for equine infectious anaemia surveillance.
AB - BACKGROUND: ELISAs are known to have a higher diagnostic sensitivity than the
agar gel immunodiffusion (AGID) when employed for serological diagnosis of equine
infectious anaemia (EIA). For this purpose, an "in-house" and five commercial
ELISAs available in Italy were assessed by the National Reference Centre for EIA
for their analytic specificity (Sp); precocity, defined as capability of
detecting first antibodies produced during a new infection; precision based on
repeatability and reproducibility, estimated from the coefficient of variation
(CV); accuracy, estimated from multiple K and relative Sp and sensitivity (Se).
Two serum panels, positive for non-equine retroviruses and the most frequent
equine viruses, were employed to measure analytic Sp. ELISA precocity was also
compared to that of one "in-house" and three commercial AGID kits, employing a
panel of sera, collected weekly from horses infected with modified EIA viruses.
Precision and accuracy were defined using results of a panel containing positive
and negative sera examined in an inter-laboratory trial with the participation of
the ten Official Laboratories. Furthermore, a questionnaire was used to assess
the appropriateness of each kit for routine use. RESULTS: Analytic Sp was 100%,
while the 75th percentile of CVs for positive sera varied from 0.4% to 12.73% for
repeatability and from 1.6% to 44.87% for reproducibility. Although CV of the
negative serum was constantly high, its outcome was unaltered. Relative Se ranged
from 98.2% to 100%, relative Sp was constantly 100% and multiple K ranged from
0.95 to 1. Precocity differed among the assays: three kits detected 4.8% and
42.9% positive samples on 21 days post infection (dpi), all assays detected
positive samples on 28 dpi, between 47.6% and 95.2%. Precocity of ELISAs was
superior to that of the AGIDs except for two assays. In view of the feedback
obtained from the questionnaires, all kits were considered appropriate for
routine use. CONCLUSION: All ELISAs having high Se and precocity are preferable
as a screening test in EIA surveillance programmes to the AGID tests examined.
These two tests can be incorporated in a serial diagnostic pathway to improve the
efficacy of a surveillance plan.
PMID- 28410614
TI - Factors associated with high-utilization in a safety net setting.
AB - BACKGROUND: Patients with frequent hospital readmissions, or high-utilizer
patients (HUPs), are a major driver of rising healthcare costs in the United
States. This group has a significant burden of medical illness, but less is known
about whether or how social determinants of health may drive their increased
healthcare use and poor health outcomes. Our study aimed to define the population
of HUPs at a large, safety-net hospital system, to understand how these patients
differ from patients who are not HUPs, and to analyze how their demographic,
medical, and social factors contribute to their healthcare use and mortality
rates. METHODS: For this case-control study, data were collected via
retrospective chart review. We included 247 patients admitted three or more times
in a single calendar year between 2011 and 2013 and 247 controls with one or two
admissions in a single calendar year matched for age, sex, and year of high
utilization. We used multivariable logistic regression models to understand which
demographic, clinical, and social factors were associated with HUP status, and if
HUP status was independently associated with mortality. RESULTS: The factors that
contributed significant odds of being a HUP included having Medicaid (OR 3.34,
95% CI 1.50, 7.44) or Medicare (OR 3.39, 95% CI 1.50, 7.67), having a history of
recreational drug use (OR 2.44, 95% 1.36, 4.38), and being homeless (OR 3.73, 95%
CI 1.69, 8.23) The mortality rate among HUPs was 22.6% compared to 8.9% among
controls (p < 0.0001). CONCLUSIONS: These data show that social factors are
related to high-utilization in this population. Future efforts to understand and
improve the health of this population need to incorporate non-clinical patient
factors.
PMID- 28410615
TI - Signal-to-noise ratio evaluation of magnetic resonance images in the presence of
an ultrasonic motor.
AB - BACKGROUND: Safe robot-assisted intervention using magnetic resonance imaging
(MRI) guidance requires the precise control of assistive devices, and most
currently available tools are rarely MRI-compatible. To obtain high precision, it
is necessary to characterize and develop existing MRI-safe actuators for use in a
high magnetic field (>=3 T). Although an ultrasonic motor (USM) is considered to
be an MRI-safe actuator, and can be used in the vicinity of a high field scanner,
its presence interferes with MR images. Although an MR image provides valuable
information regarding the pathology of a patient's body, noise, generally of a
granular type, decreases the quality of the image and jeopardizes the true
evaluation of any existing pathological issues. An eddy current induced in the
conductor material of the motor structure can be a source of noise when the motor
is close to the isocenter of the image. We aimed to assess the effects of a USM
on the signal-to-noise ratio (SNR) of MR images in a 3-T scanner. The SNR was
compared for four image sequences in transverse directions for three orientations
of the motor (x, y, and z) when the motor was in the "off" state. The SNR was
evaluated to assess three artifact reduction methods used to minimize the motor
induced artifacts. RESULTS: The SNR had a range of 5-10 dB for slices close to
the motor in the x and y orientations, and increased to 15-20 dB for slices far
from the motor. Averaging the SNR for slices in all cases gave an SNR loss of
about 10 dB. The maximum SNR was measured in the z orientation. In this case, the
SNR loss was almost the same as that of other motor orientations, approximately
10 dB, but with a higher range, approximately 20-40 dB. CONCLUSIONS: The
selection of certain scanning parameters is necessary for reducing motor
generated artifacts. These parameters include slice selection and bandwidth. In
developing any MRI-compatible assisted device actuated by a USM, this study
recommends the use of an approximately 3-mm slice thickness with minimum
bandwidth to achieve optimized SNR values when a USM is operating close to
(within approximately 40 mm) the region being imaged. The SNR can be further
enhanced by increasing the number of signal averages, but this is achieved only
at the cost of increased scan duration.
PMID- 28410616
TI - Breast masses in mammography classification with local contour features.
AB - BACKGROUND: Mammography is one of the most popular tools for early detection of
breast cancer. Contour of breast mass in mammography is very important
information to distinguish benign and malignant mass. Contour of benign mass is
smooth and round or oval, while malignant mass has irregular shape and spiculated
contour. Several studies have shown that 1D signature translated from 2D contour
can describe the contour features well. METHODS: In this paper, we propose a new
method to translate 2D contour of breast mass in mammography into 1D signature.
The method can describe not only the contour features but also the regularity of
breast mass. Then we segment the whole 1D signature into different subsections.
We extract four local features including a new contour descriptor from the
subsections. The new contour descriptor is root mean square (RMS) slope. It can
describe the roughness of the contour. KNN, SVM and ANN classifier are used to
classify benign breast mass and malignant mass. RESULTS: The proposed method is
tested on a set with 323 contours including 143 benign masses and 180 malignant
ones from digital database of screening mammography (DDSM). The best accuracy of
classification is 99.66% using the feature of root mean square slope with SVM
classifier. CONCLUSION: The performance of the proposed method is better than
traditional method. In addition, RMS slope is an effective feature comparable to
most of the existing features.
PMID- 28410617
TI - Treatment with high-dose n-3 PUFAs has no effect on platelet function,
coagulation, metabolic status or inflammation in patients with atherosclerosis
and type 2 diabetes.
AB - BACKGROUND: Despite numerous studies on cardioprotective effects of omega-3
polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA
mediated effects, especially at its higher dose, on cardiovascular risk in
patients with type 2 diabetes (DM2) and established atherosclerosis. PURPOSE: To
investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs
on platelet function, coagulation parameters, fibrin clot properties, markers of
systemic inflammation and metabolic status, in patients with atherosclerotic
vascular disease and DM2 who receive optimal medical therapy. METHODS: We
conducted a prospective, double-blind, placebo-controlled, randomized, double
center study, in which thrombin generation (plasma thrombogenic potential from
automated thrombogram), fibrin clot properties (plasma fibrin clot permeability;
lysis time), platelet aggregation (light transmission aggregometry with adenosine
diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid
profiles, leptin and adiponectin levels, as well as markers of systemic
inflammation (i.e., hsCRP, IL-6, TNF-alpha, ICAM-1, VCAM-1, and myeloperoxidase)
were determined at baseline and at 3 months after treatment with 2 g/day of n-3
PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of
the phospholipid fraction by gas chromatography both at baseline and at the end
of the study. RESULTS: Majority of patients were treated with optimal medical
therapy and achieved recommended treatment targets. Despite higher serum levels
of eicosapentaenoic acid (EPA) (by 204%; p < 0.001) and docosahexaenoic acid
(DHA) (by 62%; p < 0.0001) in n-3 PUFA group at the end of treatment no changes
in platelet aggregation, thrombin generation, fibrin clot properties or markers
of systemic inflammation were observed. No intergroup differences in the insulin,
HbA1c and lipid levels were found at the end of the study. There was no change in
adiponectin and leptin in interventional group, however leptin increased in
control group (p = 0.01), therefore after study period leptin levels were lower
in the interventional group (p = 0.01). Additionally, resolvin D1 did not differ
between interventional and control group. CONCLUSIONS: In conclusion, our study
demonstrated that in patients with long-standing, well-controlled DM2 and
atherosclerotic disease the treatment with a high dose of n-3 PUFAs (namely, 1
g/day of EPA and 1 g/day of DHA for 3 months) does not improve coagulation,
metabolic, and inflammatory status when measured with the specified tests. The
study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration
date: April 12, 2014.
PMID- 28410619
TI - FOXO1, PXK, PYCARD and SAMD9L are differentially expressed by fibroblast-like
cells in equine synovial membrane compared to joint capsule.
AB - BACKGROUND: The synovial membrane lines the luminal side of the joint capsule in
synovial joints. It maintains joint homeostasis and plays a crucial role in
equine joint pathology. When trauma or inflammation is induced in a joint, the
synovial membrane influences progression of joint damage. Equine synovial
membrane research is hampered by a lack of markers of fibroblast-like
synoviocytes (FLS) to distinguish FLS from other fibroblast-like cells in
musculoskeletal connective tissues. The aim of this study is to identify
potential FLS markers of the equine synovial membrane using microarray to compare
between gene expression in equine synovial membrane and the joint capsule in
metacarpophalangeal joints. RESULTS: Microarray analysis of tissues from 6 horses
resulted in 1167 up-regulated genes in synovial membrane compared with joint
capsule. Pathway analysis resulted in 241 candidate genes. Of these, 15 genes
were selected for further confirmation as genes potentially expressed by
fibroblast-like synoviocytes. Four genes: FOXO1, PXK, PYCARD and SAMD9L were
confirmed in 9 horses by qPCR as differentially expressed in synovial membrane
compared to joint capsule. CONCLUSIONS: In conclusion, FOXO1, PXK, PYCARD and
SAMD9L were confirmed as differentially expressed in synovial membrane compared
to joint capsule. These four genes are potential markers of fibroblast-like
synoviocytes of the synovial membrane. As these genes are overexpressed in
synovial membrane compared to joint capsule, these genes could shed light on
synovial membrane physiology and its role in joint disease.
PMID- 28410620
TI - Resolution of recurrent aphthous ulcers after discontinuation of cow's milk
protein intake.
AB - BACKGROUND AND OVERVIEW: Authors of published studies have reported elevated
levels of circulating antibodies to cow's milk protein (CMP) in patients with
recurrent aphthous ulcers (RAUs), and authors of case reports have described
resolution of RAU after dairy elimination. CASE DESCRIPTION: A 10-year-old girl
and an 11-year-old boy, both with 5-year histories of frequent RAU episodes, with
multiple ulcerations, underwent dairy elimination trials. Both were free of oral
ulcers within 2 weeks of discontinuing CMP and remained so with a CMP-free diet.
In addition, the first patient had recurrence of ulcerations after occasional
ingestion of CMP-containing foods. She showed elevated blood levels of
immunoglobulin E in reaction to CMP and soy. Soy intake did not trigger the
ulcerations. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The proportion of patients
with RAU in whom CMP acts as a trigger is unknown. However, CMP elimination
trials are safe and feasible and, therefore, should be considered, particularly
before use of medications with potential side effects.
PMID- 28410618
TI - Liquid biopsy: a step forward towards precision medicine in urologic
malignancies.
AB - There is a growing trend towards exploring the use of a minimally invasive
"liquid biopsy" to identify biomarkers in a number of cancers, including urologic
malignancies. Multiple aspects can be assessed in circulating cell-free DNA,
including cell-free DNA levels, integrity, methylation and mutations. Other
prospective liquid biopsy markers include circulating tumor cells, circulating
RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have
also emerged as non-invasive cancer biomarkers. These circulating molecules can
be detected in various biological fluids, including blood, urine, saliva and
seminal plasma. Liquid biopsies hold great promise for personalized medicine due
to their ability to provide multiple non-invasive global snapshots of the primary
and metastatic tumors. Molecular profiling of circulating molecules has been a
stepping-stone to the successful introduction of several non-invasive multi
marker tests into the clinic. In this review, we provide an overview of the
current state of cell-free DNA-based kidney, prostate and bladder cancer
biomarker research and discuss the potential utility other circulating molecules.
We will also discuss the challenges and limitations facing non-invasive cancer
biomarker discovery and the benefits of this growing area of translational
research.
PMID- 28410621
TI - Expanding the Genotype of Sjogren-Larsson Syndrome: A New Case Due to Two Novel
Mutations.
PMID- 28410622
TI - Histone deacetylase inhibitors, Thimerosal, and autism spectrum disorder.
PMID- 28410624
TI - Definition: Apraxia.
PMID- 28410625
TI - In search of a shared language in neuropsychology.
PMID- 28410623
TI - Impact of GM1 on Membrane-Mediated Aggregation/Oligomerization of beta-Amyloid:
Unifying View.
AB - In this perspective we summarize current knowledge of the effect of
monosialoganglioside GM1 on the membrane-mediated aggregation of the beta-amyloid
(Abeta) peptide. GM1 has been suggested to be actively involved in the
development of Alzheimer's disease due to its ability to seed the aggregation of
Abeta. However, GM1 is known to be neuroprotective against Abeta-induced
toxicity. Here we suggest that the two scenarios are not mutually exclusive but
rather complementary, and might depend on the organization of GM1 in membranes.
Improving our understanding of the molecular details behind the role of
gangliosides in neurodegenerative amyloidoses might help in developing disease
modifying treatments.
PMID- 28410626
TI - Definition: Limb apraxia.
PMID- 28410627
TI - Polyunsaturated Fatty Acids in Perinatal Depression: A Systematic Review and Meta
analysis.
AB - BACKGROUND: Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) are promising
antidepressant treatments for perinatal depression (PND) because of supporting
evidence from clinical trials, the advantage in safety, and their anti
inflammatory and neuroplastic effects. Although several observational studies
have shown n-3 PUFA deficits in women with PND, the results of individual PUFAs
from different studies were inconsistent. METHODS: This systematic review and
meta-analysis aims to compare the levels of PUFA indices, including
eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, total n-3, total n
6, and the n-6/n-3 ratio between women with PND and healthy control subjects. The
meta-analysis included 12 eligible studies available as of December 2016. The
effect sizes were synthesized by using a random effects model. In addition, we
performed subgroup analysis for the PUFA levels in patients with prenatal and
postnatal depression, both of which were compared with healthy control subjects.
RESULTS: There were significantly lower levels of total n-3 PUFAs and
docosahexaenoic acid and significantly increased n-6/n-3 ratios in PND patients.
In the subgroup analyses, there were significantly lower levels of n-3 PUFAs,
eicosapentaenoic acid, and docosahexaenoic acid in women with prenatal
depression. The n-6/n-3 ratio was significantly increased in both prenatal and
postnatal depression subgroups. CONCLUSIONS: Our meta-analysis consolidates the
important role of n-3 PUFAs in PND. Nutritional medicine is an important strategy
to improve the effectiveness of treatment for depression, and our findings
provide the strong rationale to conduct clinical trials to test the therapeutic
and prophylactic effects of n-3 PUFAs in PND.
PMID- 28410628
TI - Laparoscopic partial splenectomy for a splenic epidermoid cyst.
PMID- 28410629
TI - Conservative management of massive pneumoperitoneum after argon plasma
coagulation.
PMID- 28410630
TI - Tumor size as a prognostic factor in patients with stage IIa colon cancer.
AB - BACKGROUND: The aim of this study was to identify stage II colon cancer patients
with a high risk of recurrence. METHODS: All patients who underwent surgery for
stage II colon cancer (CC) were retrospectively enrolled and sub-grouped
according to TNM staging (IIa-b-c) and stage IIa in high (IIaHR) and low risk
(IIaLR) according to pathologic features. The primary outcomes measured were the
5-year overall survival (OS) and disease-free survival (DFS). RESULTS: A total of
214 patients were reviewed. Only a maximum tumor diameter<4 cm in the IIaLR group
was associated with a higher recurrence rate than a large tumor size (5-year DFS
71.7%vs.87.6%, p = 0.028). The DFS in the large IIaLR CC group was better than
that in the IIaHR and IIb-c groups (5-year DFS: 92.7%vs.79.3%, p = 0.023). In
contrast, the recurrence rate in the small IIaLR CC group was similar to that in
the IIaHR, IIb-c stage CC group. CONCLUSIONS: In stage IIa CC evaluation of the
tumor size as a prognostic factor may help identify patients who could benefit
from additional postoperative therapy.
PMID- 28410631
TI - Comparison of three caval reconstruction techniques in orthotopic liver
transplantation: A retrospective review.
AB - BACKGROUND: Classic caval reconstruction during liver transplantation involves
complete cross-clamping and resection of the recipient inferior vena cava (IVC)
followed by donor IVC interposition. Other techniques preserve the IVC, with
piggyback (PB) to the hepatic veins or side-to-side (SS) caval anastomosis.
Avoidance of cross-clamping may be beneficial for minimizing hemodynamic
instability and transfusion requirements. METHODS: Retrospective review of a
provincial transplant database (2007-2011). MELD score was used to measure
disease severity. Intraoperative blood loss and volume resuscitation were
compared between three caval reconstruction techniques using ANOVA. RESULTS: 200
deceased-donor transplants (Classic:58, PB:72, SS:70) were included. Baseline
disease severity was equal. Mean case duration was shorter in the PB technique
(Classic:366, PB:306, SS:385 min, p < 0.001). Despite similar blood loss, there
was significantly less cell saver return, FFP, platelets, and overall
resuscitation volume (Classic:12.8, PB:9.5, SS:13.2 L, p = 0.001) utilized in the
piggyback technique. CONCLUSIONS: The PB technique was faster and used less cell
saver return, FFP and platelets, despite similar blood loss. Availability of
different caval reconstruction techniques allows for a breadth of options in
difficult cases.
PMID- 28410632
TI - Evolution of Left Ventricular Size in Late Survivors of Surgery for Hypoplastic
Left Heart Syndrome.
AB - BACKGROUND: Aortic atresia and mitral atresia are predictors of adverse events in
early life in patients with hypoplastic left heart syndrome, but it is unclear
whether late outcomes are also affected, and whether this impact is related to a
small hypertrophied left ventricle (LV) that impairs right ventricle (RV)
function. METHODS: Thirty patients with hypoplastic left heart syndrome surviving
with a Fontan procedure were identified. Follow-up echocardiograms were available
at birth, before the Fontan procedure, and several years after. Mean follow-up
time was 10.9 +/- 3.1 years. Measurements included interventricular septum
thickness and ventricular length. The LV/RV length ratio at birth was calculated,
and its impact on later LV and septal growth was examined. The primary endpoint
was a composite of death, transplantation, or Fontan takedown. RESULTS: A cutoff
LV/RV length ratio of 0.55 was identified: length ratio was 0.55 or less in group
A (18 patients) and more than 0.55 in group B (12 patients) The LV/RV length
ratio and interventricular septum thickness decreased over time in group A while
remaining static in group B. The LV length at birth did not affect late adverse
outcomes (hazard ratio 2.7, 95% confidence interval: 0.31 to 23.4, p = 0.37),
whereas aortic atresia and mitral atresia were the most potent predictors of
death or transplantation or takedown (hazard ratio 8.5, 95% confidence interval:
1.2 to 57.7, p = 0.029). CONCLUSIONS: Patients with aortic atresia and mitral
atresia have worse outcomes even after Fontan independently of a small, thick,
hypertrophied LV. The most severely hypoplastic LVs do not grow proportionally as
much as the RVs.
PMID- 28410633
TI - Mean Computed Tomography Value to Predict the Tumor Invasiveness in Clinical
Stage IA Lung Cancer.
AB - BACKGROUND: The purpose of this study was to validate the ability of the mean
computed tomography (m-CT) value to predict tumor invasiveness and recurrence,
and further, to compare with other measurements such as consolidation/tumor ratio
and solid tumor size. METHODS: A retrospective study was conducted of 494
patients with clinical stage IA lung cancer who had peripherally located lung
adenocarcinoma. Receiver operating characteristic curve analysis was used to
compare the ability to predict tumor invasiveness and recurrence between m-CT
value, consolidation/tumor ratio, and tumor size. Multiple logistic regression
analyses were performed to determine the independent variables for the prediction
of pathologic, less invasive lung cancer. Disease-free survival was measured from
the date of the operation until any recurrence. RESULTS: The m-CT values were
643.6 +/- 9.4 Hounsfield units in the noninvasive cancer group and 365.9 +/- 11.4
Hounsfield units in the invasive cancer group (p < 0.0001). The invasive cancer
group was strongly associated with a high CT attenuation value, high
consolidation/tumor ratio, large solid tumor size, large tumor size, and high
standardized uptake value. Multiple logistic analyses, including the
preoperatively determined variables, revealed that standardized uptake value and
m-CT are independent predictive factors of less invasive lung cancer. In
addition, the hazard ratio of the m-CT value was higher than that of the
standardized uptake value value. CONCLUSIONS: The evaluation of m-CT value is
useful in predicting less invasive lung cancer. The m-CT value can potentially
determine operative procedure, particularly limited resection for peripheral lung
adenocarcinoma.
PMID- 28410634
TI - Three Hundred Fifty-One Patients With Pneumothorax Undergoing Uniportal (Single
Port) Video-Assisted Thoracic Surgery.
AB - BACKGROUND: Video-assisted thoracic surgery (VATS) is usually performed using
three ports. Uniportal VATS has not yet been widely developed. We report our
single institution experience in uniportal VATS for the surgical management of
351 patients with pneumothorax. METHODS: Between November 2009 and February 2016,
we conducted a study in 351 patients treated for pneumothorax using uniportal
VATS. Resection of apical bullae associated with partial pleurectomy, pleural
abrasion, or talc effusion was performed. RESULTS: The mean age was 29.6 +/- 10.1
years. Surgical indications were mainly persistence or recurrence of
pneumothorax. Sixty-seven patients (19%) presented with complications. At the 30
day control, 60.1% of patients were asymptomatic; 85% of patients were satisfied
with the single small scar. The recurrence rate was 3.6% at 24 +/- 13 months.
CONCLUSIONS: Uniportal VATS is feasible, safe, and reproducible in the treatment
of pneumothorax. Morbidity is similar to multiport VATS. The recurrence rate is
comparable with best results after multiport VATS or thoracotomy. Patients were
satisfied with the single small scar.
PMID- 28410635
TI - Severe Chronic Obstructive Pulmonary Disease Is Not Associated With Complications
After Navigational Bronchoscopy Procedures.
AB - BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) is a commonly used
technique to obtain biopsies of peripheral pulmonary lesions. Little is known
about risk factors for complications with this procedure. The aim of this study
was to assess the complication rate associated with ENB and the relationship of
complications to patient- and procedure-related factors. METHODS: Consecutive ENB
procedures at an academic medical center between May 11, 2011, and September 11,
2015, were reviewed retrospectively. Preoperative characteristics, including
pulmonary function, procedure characteristics, and the occurrence of
complications, were recorded. RESULTS: In all, 361 procedures were performed on
341 patients. Complications occurred in 30 of 361 (8.3%), the most common of
which was pneumothorax (27, 7.5%). Complications were not related to age, sex,
American Society of Anesthesiologists grade, or pulmonary function test result.
Patients with complications had longer procedure times (50 versus 73 minutes, p =
0.03), and had more interventional modalities used (2.4 versus 3.2, p = 0.001).
Multiple logistic regression demonstrated that bronchoalveolar lavage was
significantly associated with complications (odds ratio 6.40; 95% confidence
interval: 1.68 to 24.3, p = 0.006). CONCLUSIONS: Electromagnetic navigational
bronchoscopy is safe, and the rate of complications is not elevated among
patients with poor lung function. Bronchoalveolar lavage performed during ENB was
associated with elevated risk of complications and should be studied further.
PMID- 28410636
TI - Stent and Leaflet Stresses in 29-mm Second-Generation Balloon-Expandable
Transcatheter Aortic Valve.
AB - BACKGROUND: Equipoise of transcatheter aortic valve replacement with surgical
aortic valve replacement in intermediate-risk patients has been demonstrated. As
transcatheter aortic valve replacement usage expands, questions regarding long
term durability become paramount. Valve design impacts durability with regions of
increased leaflet stress being vulnerable to early failure. However,
transcatheter aortic valve (TAV) leaflet stresses are unknown. The objective of
this study was to determine stent and leaflet stresses of second-generation
balloon-expandable TAV. METHODS: Commercial 29-mm Edwards Sapien XT (Edwards
Lifesciences, Irvine, CA) valves underwent high-resolution microcomputed
tomography scanning to develop precise three-dimensional geometric mesh.
Compressed and uncompressed TAVs were modeled under systemic pressure using
finite element software. Material properties of stent were based on cobalt
chromium, whereas those for leaflets were obtained from surgical bioprostheses.
RESULTS: Maximum and minimum principal stresses on uncompressed Sapien XT TAV
were 1.63 MPa and -0.36 MPa on leaflets and 93.3 MPa and -105.6 MPa on stent at
diastolic pressure. Peak leaflet stress was observed at commissural tips where
leaflets connected to the stent. For compressed TAV to 26 mm, maximum and minimum
principal stresses were 1.55 MPa and -0.63 MPa on leaflets and 526.1 MPa and
902.2 MPa on stent at diastolic pressure. Peak leaflet stress was located at
similar position and also along the suture line with the Dacron (C. R. Bard,
Haverhill, PA). CONCLUSIONS: Stress analysis of two extreme deployed geometries
of 29-mm Edwards Sapien XT using exact geometry from high-resolution scans
demonstrated that peak stresses for TAV leaflets were present at commissural tips
where leaflets were attached. These regions would be mostly likely to initiate
degeneration.
PMID- 28410637
TI - The Influence of Physician and Patient Gender on Risk Assessment for Lung Cancer
Resection.
AB - BACKGROUND: Women do not receive appropriate surgical therapy for lung cancer as
often as men. Patient gender may influence treatment recommendations; less is
known about the effect of physician gender on recommendations. METHODS: Gender
neutral vignettes representing low-risk, average-risk, and high-risk candidates
for lung resection were paired with concordant videos of standardized patients
(SPs). Cardiothoracic trainees and practicing thoracic surgeons read a vignette,
provided an initial estimate of the percentage risk of major adverse events after
lung resection, viewed a video (randomized to male or female SP), provided a
final estimate of risk, and ranked the importance of the video in the final risk
estimate. RESULTS: Overall, 107 surgeons participated, of whom 90 were men.
Initial estimated risks mirrored actual vignette risks: 10.4% +/- 9.9 for low
risk, 17.6% +/- 13.2 for average risk, and 21.0% +/- 14.7 for high risk (p <
0.001). After SP videos were viewed and final risk estimates were rendered, there
was a significant difference between male and female physicians in the absolute
change in estimated risk (p = 0.002), with male physicians having larger changes
than female physicians. There was also an effect of SP gender that varied by
vignette type (p < 0.001). Increasing video importance scores were directly
associated with increasing change in risk scores for average-risk and high-risk
vignette/video combinations (p < 0.001 for each). CONCLUSIONS: Differences in
estimating complication risk for lung resection candidates are related to
physician and patient gender. This may influence recommendations for surgical
treatment. Understanding such differences may help reduce inequities in treatment
recommendations.
PMID- 28410638
TI - Utility of Objective Chest Tube Management After Pulmonary Resection Using a
Digital Drainage System.
AB - BACKGROUND: We sought to evaluate the clinical utility of chest tube management
after pulmonary resection based on objective digital monitoring of pleural
pressure and digital surveillance for air leaks. METHODS: We prospectively
recorded the perioperative data of 308 patients who underwent pulmonary resection
between December 2013 and January 2016. We used information from a digital
monitoring thoracic drainage system to measure peak air leakage during the first
24 hours after the operation, patterns of air leakage over the first 72 hours,
and patterns of pleural pressure changes until the chest tubes were removed.
RESULTS: There were 240 patients with lung cancer and 68 patients with other
diseases. The operations included 49 wedge resections, 58 segmentectomies, and
201 lobectomies. A postoperative air leak was observed in 61 patients (20%). A
prolonged air leak exceeding 20 mL/min lasting 5 days or more was observed in 18
patients (5.8%). Multivariate analysis of various perioperative factors showed
forced expiratory volume in 1 second below 70%, patterns of air leakage, defined
as exacerbating and remitting or without a trend toward improvement, and peak air
leakage of 100 mL/min or more were significant positive predictors of prolonged
air leak. Fluctuations in pleural pressure occurred just after the air leakage
rate decreased to less than 20 mL/min. CONCLUSIONS: Digital monitoring of peak
air leakage and patterns of air leakage were useful for predicting prolonged air
leak after pulmonary resection. Information on the disappearance of air leak
could be derived from the change in the rate of air leakage and from the increase
in fluctuation of pleural pressure.
PMID- 28410639
TI - Socioeconomic Status, Not Race, Is Associated With Reduced Survival in
Esophagectomy Patients.
AB - BACKGROUND: Black patients with esophageal cancer have worse survival than white
patients. This study examines this racial disparity in conjunction with
socioeconomic status (SES) and explores whether race-based outcome differences
exist using a national database. METHODS: The associations between race and SES
with overall survival of patients treated with esophagectomy for stages I to III
esophageal cancer between 2003 and 2011 in the National Cancer Data Base were
investigated using the Kaplan-Meier method and proportional hazards analyses.
Median income by zip code and proportion of the zip code residents without a high
school diploma were grouped into income and education quartiles, respectively and
used as surrogates for SES. The association between race and overall survival
stratified by SES is explored. RESULTS: Of 11,599 esophagectomy patients who met
study criteria, 3,503 (30.2%) were in the highest income quartile, 2,847 (24.5%)
were in the highest education quartile, and 610 patients (5%) were black. Before
adjustment for SES, black patients had worse overall survival than white patients
(median survival 23.0 versus 34.7 months, log rank p < 0.001), and overall,
survival times improved with increasing income and education (p < 0.001 for
both). After adjustment for putative prognostic factors, SES was associated with
overall survival, whereas race was not. CONCLUSIONS: Prior studies have suggested
that survival of esophageal cancer patients after esophagectomy is associated
with race. Our study suggests that race is not significantly related to overall
survival when adjusted for other prognostic variables. Socioeconomic status,
however, remains significantly related to overall survival in our model.
PMID- 28410640
TI - Florida Sleeve Procedure Is Durable and Improves Aortic Valve Function in Marfan
Syndrome Patients.
AB - BACKGROUND: The Florida sleeve (FS) procedure was developed as a simplified
approach for repair of functional type I aortic insufficiency secondary to aortic
root aneurysm. We evaluated postoperative aortic valve function, long-term
survival, and freedom from reoperation in Marfan syndrome patients who underwent
the FS procedure at our center. METHODS: All Marfan syndrome patients undergoing
FS procedure from May 2002 to December 2014 were included. Echocardiography
assessment included left ventricular end-diastolic diameter (LVEDD), left
ventricular end-systolic diameter (LVESD), ejection fraction, and degree of
aortic insufficiency (none = 0, minimal = 1, mild = 2, moderate = 3, severe = 4).
Social Security Death Index and primary care physicians' report were used for
long-term follow-up. RESULTS: Thirty-seven Marfan syndrome patients, 21 (56.8%)
men and 16 (43%) women with mean age of 35.08 +/- 13.45 years underwent FL repair
at our center. There was no in-hospital or 30-day death or stroke. Two patients
required reoperation due to bleeding. Patients' survival rate was 94% at 1 to 8
years. Freedom from reoperation was 100% at 8 years. Twenty-five patients had
postoperative follow-up echocardiography at 1 week. Aortic insufficiency grade
significantly decreased after the procedure (preoperative mean +/- SD: 1.76 +/-
1.2 versus 1-week postoperative mean +/- SD: 0.48 +/- 0.71, p < 0.001), and mean
LVEDD decreased from 52.23 +/- 5.29 mm to 47.53 +/- 8.89 mm (p = 0.086). Changes
in LVESD (35.33 +/- 9.97 mm to 36.58 +/- 9.82 mm, p = 0.58) and ejection fraction
(57.65% +/- 6.22% to 55% +/- 10.83%, p = 0.31) were not significant. CONCLUSIONS:
The FS procedure can be performed safely in Marfan syndrome patients with
immediate improvement in aortic valve function. Long-term survival and freedom
from reoperation rates are encouraging.
PMID- 28410641
TI - A Comparative Analysis of Survival Prediction Using PRESERVE and RESP Scores.
AB - BACKGROUND: Venovenous (VV) extracorporeal membrane oxygenation (ECMO) can be a
life-saving therapy for patients with severe acute lung failure refractory to
conventional therapy. The respiratory ECMO survival prediction (RESP) score and
the predicting death for severe acute respiratory distress syndrome on VV-ECMO
(PRESERVE) score were created to predict survival at the time of initiation of
ECMO. This study aimed to validate both of these scores externally and to compare
their predictive accuracies in patients with non-Western acute respiratory
distress syndrome (ARDS). METHODS: In this retrospective cohort study, we
reviewed and extracted data from electronic medical records of consecutive adult
ARDS patients who were treated with VV-ECMO from 2007 to 2015. The PRESERVE and
RESP scores were calculated for each patient. The outcomes of interest were
inhospital and 6-month survival. RESULTS: In all, 99 patients were included. The
mean age of the patients was 54 years, and male patients constituted 70% of the
cohort. The inhospital and 6-month survival rates were 23% and 22%, respectively.
Receiver-operating characteristics curve analysis of the PRESERVE and RESP scores
showed area under the curve values of 0.64 and 0.69, respectively (p = 0.53), for
inhospital survival. The receiver-operating characteristics areas under the curve
for 6-month survival were 0.66 and 0.69, respectively (p = 0.68). The prognostic
accuracies of the PRESERVE and RESP scores were thus similar. CONCLUSIONS: Both
PRESERVE and RESP scores are useful for predicting survival in Asian ARDS
patients, and both scores had similar prognostic accuracies in our Korean ARDS
cohort.
PMID- 28410644
TI - Optimizing the Transition to End-Stage Renal Disease.
PMID- 28410643
TI - High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem
Cells.
AB - Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the
possibility of studying the molecular mechanisms underlying human diseases in
cell types difficult to extract from living patients, such as neurons and
cardiomyocytes. To date, studies have been published that use small panels of
iPSC-derived cell lines to study monogenic diseases. However, to study complex
diseases, where the genetic variation underlying the disorder is unknown, a
sizable number of patient-specific iPSC lines and controls need to be generated.
Currently the methods for deriving and characterizing iPSCs are time consuming,
expensive, and, in some cases, descriptive but not quantitative. Here we set out
to develop a set of simple methods that reduce cost and increase throughput in
the characterization of iPSC lines. Specifically, we outline methods for high
throughput quantification of surface markers, gene expression analysis of in
vitro differentiation potential, and evaluation of karyotype with markedly
reduced cost.
PMID- 28410642
TI - iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of
Genetic Variation across a Variety of Cell Types.
AB - Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as
powerful model systems for examining how genetic variation affects biology and
disease. Here we describe the iPSCORE resource: a collection of systematically
derived and characterized iPSC lines from 222 ethnically diverse individuals that
allows for both familial and association-based genetic studies. iPSCORE lines are
pluripotent with high genomic integrity (no or low numbers of somatic copy-number
variants) as determined using high-throughput RNA-sequencing and genotyping
arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC
derived cardiomyocytes demonstrate gene expression patterns that cluster by
genetic background, and can be used to examine variants associated with
physiological and disease phenotypes. The iPSCORE collection contains
representative individuals for risk and non-risk alleles for 95% of SNPs
associated with human phenotypes through genome-wide association studies. Our
study demonstrates the utility of iPSCORE for examining how genetic variants
influence molecular and physiological traits in iPSCs and derived cell lines.
PMID- 28410645
TI - Epidemiology and Risk Factors for Early Mortality After Dialysis Initiation.
AB - Confronted with the decision to initiate dialysis, patients and caregivers often
seek information about how expected survival chances evolve, both initially and
afterward, providing the patient survives beyond arbitrary periods of time. Large
registry data, used to examine these issues, may be subject to early
ascertainment bias, such as those accruing from nonregistration of with end-stage
kidney disease who die shortly after dialysis initiation and inclusion of
patients with acute kidney injury with slower than typical recovery rates.
Despite these caveats, available studies have suggested that mortality hazards
are much higher in the first 3 months of renal replacement therapy. Prominent
modifiable associations of early mortality include late referral to nephrology
services, initial dialysis with vascular catheters, and, most problematically,
higher glomerular filtration rates at initiation of renal replacement therapy.
Despite their imperfections, currently available information is relatively user
unfriendly and could be better leveraged to help patients and treatment teams
make better decisions.
PMID- 28410647
TI - Disease Trajectories Before ESRD: Implications for Clinical Management.
AB - One of the biggest challenges nephrologists face is to predict complex clinical
pathways of kidney disease progression that do not follow a steady linear
decline. This unpredictability often becomes a barrier to timely shared decision
making between patients and physicians and could lead to adverse patient
outcomes. By using numerous analytic approaches to characterize the longitudinal
changes in kidney function, emerging evidence has disclosed the heterogeneous
trajectories of kidney disease progression, particularly in late-stage chronic
kidney disease (CKD) nearing end-stage renal disease (ESRD), and showed their
independent associations with various clinical outcomes. These findings, in turn,
have reinforced the importance of incorporating individual kidney disease
trajectories into the clinical management of patients with late-stage CKD, which
may help clarify the optimal timing of preparatory interventions, such as
vascular access planning and transplant referral, and deliver better care with
potential downstream benefits, such as a lower incidence of ESRD or a more
seamless transition to ESRD. In this article, we review the current evidence on
trajectories of kidney disease progression, particularly among patients with late
stage CKD progressing to ESRD, and discuss their implications for clinical
management.
PMID- 28410648
TI - Risk Prediction Models in CKD.
AB - Chronic kidney disease (CKD) currently affects 20 million Americans and is
associated with increased morbidity and mortality. Resource-efficient and
appropriate treatment of CKD benefits the patient and provides improved resource
allocation for the health care system. Prediction models can be useful in
efficiently allocating resources, and currently are being used at the bedside for
several important clinical decisions. There is a paucity of prediction models in
use in nephrology, but one such model, the Kidney Failure Risk Equation, uses
routinely collected laboratory values and can inform clinical decisions related
to the following: (1) triage of nephrology referrals, (2) evaluating the need for
more intensive interdisciplinary clinic care, (3) determining the timing of
modality education, and (4) dialysis access planning. The development of new
models that predict survival and quality of life on dialysis, success on home
modalities, failure of arteriovenous fistulas, and risk of cardiovascular disease
in patients with CKD is needed.
PMID- 28410646
TI - Evolution of Cardiovascular Disease During the Transition to End-Stage Renal
Disease.
AB - Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality
in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD).
The rate of death in incident dialysis patients remains high. This has led to
interest in the study of the evolution of CVD during the critical transition
period from CKD to ESRD. Understanding the natural history and risk factors of
clinical and subclinical CVD during this transition may help guide the timing of
appropriate CVD therapies to improve outcomes in patients with kidney disease.
This review provides an overview of the epidemiology of subclinical and clinical
CVD during the transition from CKD to ESRD and discusses clinical trials of CVD
therapies to mitigate risk of CVD in CKD and ESRD patients.
PMID- 28410649
TI - Incident Dialysis Access in Patients With End-Stage Kidney Disease: What Needs to
Be Improved.
AB - The initiation of dialysis is a challenging time of transition for patients,
families, and their supporters. Patients with exposure to a comprehensive chronic
kidney disease clinic may have had education and subsequent decision making
regarding dialysis modality and access; however, many patients with or without
prior education will require an urgent start to dialysis, requiring quick
decisions regarding dialysis modality and access. In many countries, hemodialysis
(HD) using a central venous catheter (CVC) is the most common initial renal
replacement modality and dialysis access. Multiple factors, both remedial and
nonremedial, contribute to this including late referral, rapid decrease in kidney
function, delay in delivery or acceptance of education, and decision making and
other system delays. Recent use of urgent peritoneal dialysis as the initial
dialysis modality has resulted in decreased exposure to CVCs and in-center HD.
This article addresses the current state of incident dialysis access, recent
trends toward urgent peritoneal dialysis start, and opportunities to avoid the
use of CVCs for HD when appropriate, with a focus on considering dialysis access
as a critical component of the end-stage kidney disease life-plan, which requires
consideration of future modalities and access when making the choice of the
initial dialysis access.
PMID- 28410651
TI - Advance Care Planning for Patients Approaching End-Stage Kidney Disease.
AB - Patients with chronic kidney disease typically suffer a cascade of comorbid
conditions, the magnitude of which have formidable impact on advance care
planning (ACP). Complex health care decisions are complicated further by
contextual issues that may change over time. A dynamic and evolving process, ACP
ideally begins early in the continuum of chronic kidney disease, long before end
stage kidney disease is reached. Planning ahead for care is preparatory to making
decisions about kidney replacement therapy and can make for a smooth transition
in addition to preventing the start of dialysis by default. This article
addresses the key components and unique aspects of ACP for patients approaching
dialysis, highlighting the importance of shared decision making, and its effect
on the execution of multiple aspects of transition.
PMID- 28410650
TI - Prehabilitation for the Frail Patient Approaching ESRD.
AB - Frailty is a distinct phenotype that is highly prevalent in chronic kidney
disease (CKD) and appears to be more prevalent with decreasing glomerular
filtration rate. Exercise training or intervention to increase physical activity
may ameliorate poor physical functioning and frailty, and even may improve
survival in patients with CKD. Although exercise interventions improve outcomes
across the spectrum of CKD, including patients treated with dialysis, patients
treated with dialysis face barriers to exercise that patients with predialysis
CKD do not. Rehabilitation at earlier stages of CKD (or prehabilitation before
dialysis) might be more beneficial than not addressing the decreasing physical
functioning and low physical activity until patients are receiving dialysis. This
review summarizes available literature on frailty in the CKD and end-stage renal
disease population, including exercise interventions and the limited evidence for
prehabilitation as a strategy.
PMID- 28410653
TI - Ensuring Patient Safety During the Transition to ESRD.
AB - Patients with chronic kidney disease (CKD) are at risk for complications both
inherent to the disease and as a consequence of its treatment. The dangers that
CKD patients face change across the spectrum of the disease. Providers who are
well-versed in these safety threats are best poised to safeguard patients as
their CKD progresses.
PMID- 28410652
TI - Timing of Dialysis Initiation: What Has Changed Since IDEAL?
AB - The optimal timing of initiation of maintenance dialysis in patients with end
stage renal disease currently is unknown. This transition period is one of
exceptionally high vulnerability for patients; annual mortality rates in stage 5
chronic kidney disease through the first year of maintenance dialysis exceed 20%.
The results of the Initiating Dialysis Early and Late (IDEAL) study, a randomized
trial that tested the impact of dialysis initiation at two different levels of
kidney function on outcomes, showed no significant difference in survival or
other patient-centered outcomes between treatment groups. These data have
challenged the established paradigm of using estimates of glomerular filtration
as the primary guide for initiation of maintenance dialysis and illustrate the
compelling need for research to optimize the high-risk transition period from
chronic kidney disease to end-stage renal disease. This article reviews the
findings of the IDEAL study and summarizes the evolution of research findings,
updated clinical practice guidelines, and trends in dialysis initiation practices
in the United States in the 6 years since the publication of the results from
IDEAL. Complementary strategies to the use of estimated glomerular filtration
rate to optimally time the initiation of maintenance dialysis and potentially
improve patient-centered outcomes also are considered.
PMID- 28410654
TI - Update on Alzheimer's and the Dementias: Introduction.
AB - Though the numbers of dementia cases are rising worldwide, there is evidence that
incidence rates are decreasing. We now know that the neuropathological changes of
Alzheimer's disease (AD) precede overt clinical signs by 15 to 20 years and we
have biochemical and imaging markers that enable us to identify them. The genetic
complexity of AD suggests it is not a single entity but rather represents a group
of related diseases. The amyloid cascade hypothesis has led to the development of
putative disease-modifying interventions but these have not yet been demonstrated
to be substantively effective and additional approaches are warranted.
PMID- 28410656
TI - The Role of Neuropsychology in the Assessment of the Cognitively Impaired
Elderly.
AB - Cognitive abilities decline with age and older adults, as a group, are at
increased risk for developing age-related cognitive disorders. Neuropsychological
evaluation provides objective quantification of the type and severity of
cognitive deficits that can affect the elderly population and elucidates a
pattern of scores that provides diagnostic clues regarding etiology. It can also
detect mild cognitive impairment that may not be evident on bedside assessment or
mental status examination and provides critical information regarding the
progression of cognitive changes through serial evaluations. Such information
assists in counseling patients and family members and can guide therapeutic
decisions.
PMID- 28410657
TI - Assessment of the Hispanic Cognitively Impaired Elderly Patient.
AB - Hispanics are the largest minority group in the United States, approximately 7%
of the population older than 65. They often encounter challenges related to
health care access and quality of care. The prevalence of dementia among
Hispanics is higher than that of non-Hispanic whites and they frequently present
at a more advanced stage of illness. Cognitive evaluation should take into
account sociodemographic information and cultural factors to avoid misdiagnosis
and guide management. A provider who has knowledge of Hispanic culture should
conduct the neuropsychological assessment, and tests used to measure cognitive
functioning should be developed for Hispanics in the United States.
PMID- 28410655
TI - Tau Spread, Apolipoprotein E, Inflammation, and More: Rapidly Evolving Basic
Science in Alzheimer Disease.
AB - To date, Alzheimer disease drug candidates have produced negative results in
human trials, and progress in moving new targets out of the laboratory and into
trials has been slow. However, based on 3 decades of previous work, there is
reason to hope that amyloid-based and other novel therapies will move at a faster
pace toward successful clinical trials. This article highlights selected
preclinical research topics that are rapidly advancing in the laboratory.
PMID- 28410658
TI - The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly.
AB - This article reviews the current diagnostic tools that are available for
structural, functional, and molecular imaging of the brain, summarizing some of
the key findings that have been reported in individuals diagnosed with Alzheimer
disease, mild cognitive impairment, prodromal AD, or other prevalent dementias.
Given recent advances in the development of amyloid PET tracers, current
guidelines for the use of amyloid PET imaging in patients with cognitive
complaints are reviewed. In addition, data addressing the potential value of
amyloid PET imaging in the clinical setting are highlighted.
PMID- 28410660
TI - Late-Onset Alzheimer Disease.
AB - The oldest-old represent the fastest growing segment of society, and the risk of
developing dementia continues to increase with advancing age into the 9th and
10th decades of life. The most common form of dementia in the oldest-old is
Alzheimer disease (AD), although there are often mixed pathologies contributing
to dementia in addition to amyloid plaques and neurofibrillary tangles.
Diagnosing AD in the oldest-old is challenging due to cognitive and physical
changes associated with aging. Treatment remains supportive, with current
approved medications able to provide modest symptomatic benefit but unable to
slow the progression of disease.
PMID- 28410659
TI - Early-Onset Alzheimer Disease.
AB - Early-onset Alzheimer disease (EOAD), with onset in individuals younger than 65
years, although overshadowed by the more common late-onset AD (LOAD), differs
significantly from LOAD. EOAD comprises approximately 5% of AD and is associated
with delays in diagnosis, aggressive course, and age-related psychosocial needs.
One source of confusion is that a substantial percentage of EOAD are phenotypic
variants that differ from the usual memory-disordered presentation of typical AD.
The management of EOAD is similar to that for LOAD, but special emphasis should
be placed on targeting the specific cognitive areas involved and more age
appropriate psychosocial support and education.
PMID- 28410661
TI - Vascular Contributions to Cognitive Impairment in Late Life.
AB - Cerebrovascular disease (CVD) is the second leading cause of cognitive impairment
in late life. Structural neuroimaging offers the most sensitive and specific
biomarkers for hemorrhages and infarcts, but there are significant limitations in
its ability to detect microvascular disease, microinfarcts, dynamic changes in
the blood-brain barrier, and preclinical cerebrovascular disease. Autopsy studies
disclose the common co-occurrence of vascular and neurodegenerative conditions,
suggesting that in late life, a multifactorial approach to cognitive impairment
may be more appropriate than traditional dichotomous classifications. Management
of vascular risk factors remains a proven and practical approach to reducing
acute and progressive cognitive impairment and dementia.
PMID- 28410662
TI - Lewy Body Disorders.
AB - Dementia syndromes associated with Lewy bodies are subdivided into dementia with
Lewy bodies (DLB), an underdiagnosed cause of dementia in the elderly, and
Parkinson disease with dementia (PDD), cognitive impairment appearing in people
diagnosed with Parkinson disease. Their neuropathologic substrates are the
widespread distribution of aggregates of the protein alpha-synuclein in neurons
in cortical brain regions, accompanied by variable Alzheimer pathology. Clinical
features of DLB and PDD include distinctive changes in cognition, behavior,
movement, sleep, and autonomic function. Diagnostic criteria for DLB and PDD
incorporate these features. Current treatment options for DLB and PDD are
symptomatic.
PMID- 28410664
TI - Alzheimer and the Dementias.
PMID- 28410665
TI - Impact of dietary precursor ALA versus preformed DHA on fatty acid profiles of
eggs, liver and adipose tissue and expression of genes associated with hepatic
lipid metabolism in laying hens.
AB - Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), including alpha-linolenic
acid (ALA) and preformed longer chain PUFA (LCPUFA, particularly docosahexaenoic
acid, DHA) differ in their egg LCPUFA enrichment efficiency. However, mechanisms
leading to these differences are unclear. To this end, omega-3 PUFA contents in
different lipid classes, including triacylglycerol (TAG) and total phospholipid
(PL) in yolk, liver and adipose, as well as the expression of key hepatic enzymes
in lipid metabolism were evaluated in laying hens in response to changes in
dietary supply. Seventy Lohmann hens (n=10/treatment) consumed either a control
diet (0.03% total omega-3 PUFA), or the control with supplementation (0.20%,
0.40% and 0.60% total omega-3 PUFA) from either flaxseed oil or algal product, as
sources of ALA (precursor) or DHA (preformed), respectively. The study was
arranged in a completely randomized design, and data were analyzed using the Proc
Mixed procedure of SAS. ALA accumulated as a function of intake (P<0.0001) in
total and lipid classes of yolk, liver and adipose (TAG only) for ALA- and DHA
fed hens. Unlike flaxseed oil, preformed-DHA contributed to greater (P<0.0001)
accumulation of LCPUFA in yolk total PL and TAG pool, as well as adipose TAG.
This may relate to elevated (P<0.0001) expression of acyl-CoA synthetase (ACSL1).
No difference in hepatic EPA level in total lipids was noted between both
treatment groups; EPAliver=2.1493x-0.0064; R2=0.70, P<0.0001 (x=dietary omega-3
PUFA). The latter result may highlight the role of hepatic EPA in the regulation
of LCPUFA metabolism in laying hens.
PMID- 28410666
TI - A new CysLT1 and CysLT2 receptors-mediated anaphylaxis guinea pig model.
AB - Although the effectiveness of CysLT1 receptor antagonists on asthma has been
clinically established, the effects of CysLT2 receptor antagonists are still
unclear. The purpose of this study was to develop a new CysLT1 and CysLT2
receptors-mediated anaphylaxis guinea pig model using S-hexyl GSH, a gamma
glutamyl transpeptidase (GTP) inhibitor, to suppress conversion of LTC4 to LTD4.
Actively sensitized guinea pigs were challenged with OVA in the absence or
presence of S-hexyl GSH, and survival rate following anaphylactic response was
monitored. OVA-induced fatal anaphylaxis in the absence of S-hexyl GSH was almost
completely inhibited by montelukast, a CysLT1 receptor antagonist, but not by the
CysLT2 receptor antagonist BayCysLT2RA. However, under treatment with S-hexyl
GSH, the inhibitory effect of motelukast was dramatically diminished, whereas
that of BayCysLT2RA was markedly increased. The dual CysLT1/2 receptor antagonist
ONO-6950 effectively inhibited anaphylactic response in both S-hexyl GSH-treated
and non-treated animals. LC/MS/MS analysis revealed that S-hexyl GSH treatment
actually inhibited LTC4 metabolism in the blood and lung tissues. Using S-hexyl
GSH, we developed a novel CysLT1 and CysLT2 receptors-mediated anaphylaxis guinea
pig model that can be useful for not only screening both CysLT2 and CysLT1/2
receptors antagonists, but also for functional analysis of CysLT2 receptors.
PMID- 28410663
TI - Frontotemporal Dementia.
AB - Frontotemporal dementia (FTD) is a heterogeneous disorder with distinct clinical
phenotypes associated with multiple neuropathologic entities. Presently, the term
FTD encompasses clinical disorders that include changes in behavior, language,
executive control, and often motor symptoms. The core FTD spectrum disorders
include behavioral variant FTD, nonfluent/agrammatic variant primary progressive
aphasia, and semantic variant PPA. Related FTD disorders include frontotemporal
dementia with motor neuron disease, progressive supranuclear palsy syndrome, and
corticobasal syndrome. In this article, the authors discuss the clinical
presentation, diagnostic criteria, neuropathology, genetics, and treatments of
these disorders.
PMID- 28410667
TI - Comparative effects of high oleic acid vs high mixed saturated fatty acid
obesogenic diets upon PUFA metabolism in mice.
AB - Emerging evidence indicates that the fatty acid composition of obesogenic diets
influences physiologic outcomes. There are scant data regarding how the content
of non-essential fatty acids like monounsaturated fatty acids (MUFA) and
saturated fatty acids (SFAs) impact the metabolism of polyunsaturated fatty acids
(PUFAs). In this work, we tested the hypothesis that obesogenic diets enriched in
oleic acid (OA; 18:1n-9) reduce polyunsaturated fatty acid (PUFA) levels vs an
obesogenic diet enriched in SFAs. Adult male mice were fed for eight weeks either
(1) a control 16% fat energy (en) diet with 5.7% en OA and 4.4% en SFA, (2) a 50%
fat en diet with 33% en OA and 9.9% en SFA, or (3) a 50% en diet with a high SFA
diet with 33% en SFA and 9.1% en OA. Dietary levels and intake of linoleic acid
(LA; 18:2n-6) and alpha-linolenic acid (ALA; 18:3n-3) were constant between the
experimental groups. Several peripheral organs (liver, heart, kidney, and
adipose) were analyzed for lipid composition and oxylipin analysis was performed
for liver and adipose. Our data demonstrate that a high OA diet reduced tissue
content of LA and ALA (>=30%) in phospholipid and neutral lipid fractions,
reduced the content of some LA-derived and ALA-derived oxylipins in liver and
adipose, and conversely, elevated hepatic content of PGF2alpha. In all tissues
examined, except for adipose, levels of arachidonic acid (ARA; 20:4n-6) and
docosahexaenoic acid (DHA; 22:6n-3) were either elevated or unaffected by the
obesogenic diets. Our data indicate that the non-essential fatty content of
obesogenic diets impacts PUFA content in peripheral tissues and influences the
levels of bioactive oxylipins.
PMID- 28410669
TI - Curcumin and linseed oil co-delivered in phospholipid nanoemulsions enhances the
levels of docosahexaenoic acid in serum and tissue lipids of rats.
AB - Docosahexaenoic acid (DHA) is an important long chain omega-3 polyunsaturated
fatty acid (PUFA) primarily found in marine fishes. The diets of vegetarian
population do not contain preformed DHA, but they can derive it from shorter
chain alpha-linolenic acid (ALA) found in plant oils. However, the conversion
efficiency of ALA to DHA is minimal in human adults. This may cause insufficiency
of DHA in the vegetarian population. Curcumin, diferuloyl methane found in the
spice turmeric, has the potential to increase the formation of DHA from ALA by
activating the enzymes FADS2 and elongase 2. The present study was designed to
prepare curcumin nanoemulsion using phospholipid core material (LipoidTM) and
exploring the possibility of enhancing its bioavailability and its impact on DHA
levels in rats. Curcumin was dissolved in coconut oil (CNO, MCFA rich), Sunflower
oil (SNO, n-6 PUFA rich) or Linseed oil (LSO, n-3 PUFA rich) and nanoemulsions
were prepared after mixing with LipoidTM using high pressure homogenizer. The
nanoemulsions were fed to weaning rats for 60 days along with AIN-93 diets. Rats
fed nanoemulsion containing curcumin in LSO showed high levels of curcumin in
serum liver, heart and brain. Significant increase in DHA levels of serum and
tissue lipids were observed in rats given LSO with curcumin in nanoemulsions.
Therefore, supplementation of diets with ALA rich LSO and curcumin could increase
DHA concentrations in serum, liver, heart and brain lipids which have
implications for meeting the DHA requirements of vegetarian populations.
PMID- 28410668
TI - Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid
supplementation: A pilot study.
AB - Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major
depression. We examined effects of six weeks of fish oil supplementation on
clinical characteristics in 16 patients with symptomatic major depressive
disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and
eicosapentaenoic acid (EPA) as correlates of clinical response. Depression
symptoms improved after supplementation (p=0.007). The reduction in depression
severity was not predicted by baseline PUFA levels but did exhibit a relationship
with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma
phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and
correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for
endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the
reduction in depression severity (r=-0.43, p=0.097). Five patients showed a
decrease of >50% on the 17-item Hamilton Depression Rating Scale and a final
score <7 and were thus not only responders but met standard criteria for
remission, and were distinguished from non-responders by higher levels of DHA%
(p=0.03). This pilot study suggests that post-supplementation DHA% levels may be
a necessary target for antidepressant response to fish oil, and that this may
depend to some extent on the efficacy of EPA conversion to DHA.
PMID- 28410670
TI - Characterisation and intracellular labelling of mesenchymal stromal cells derived
from synovial fluid of horses and sheep.
AB - Multipotent mesenchymal stromal cells (MSCs) derived from synovial fluid (SF) are
considered to be a promising cell type for therapeutic applications in joint
disease. However, despite their potential relevance for clinical and experimental
studies, there is insufficient knowledge about SF-derived MSCs isolated from
horses and sheep. In this study, cells were recovered from healthy SF and bone
marrow (BM) of sheep, and from healthy and osteoarthritic SF of horses. Ovine SF
MSCs were used to assess the efficiency of intracellular labelling with quantum
dots (QDs). Colony forming units, generation times, trilineage differentiation
potential and expression of CD73, CD90 and CD105 at mRNA level were assessed. QD
labelling was efficient, with >98% positive cells directly after labelling at 10
nmol/L and >95% positive cells directly after labelling at 2 nmol/L. The label
decreased over 7 days of culture, with more persistence at the higher labelling
concentration. No significant differences in proliferation were observed. All
MSCs had trilineage differentiation potential, but adipogenesis was more distinct
in equine samples and chondrogenesis was most pronounced in ovine SF-MSCs. CD73,
CD90 and CD105 were expressed in equine and ovine MSCs.
PMID- 28410671
TI - Dog erythrocyte antigens (DEA) 1, 4, 7 and suspected naturally occurring anti-DEA
7 antibodies in Italian Corso dogs.
AB - We sought to determine the prevalence of dog erythrocyte antigen (DEA) 1, 4 and 7
and naturally occurring anti-DEA7 antibodies in Italian Corso dogs. In addition,
we correlated DEAs with different epidemiologic variables, compared the
prevalence of DEAs against other canine populations and assessed the risk of
sensitisation and transfusion reactions (TRs) following unmatched transfusion.
Blood samples from 100 Corso dogs were evaluated for DEA 1, 4, 7 and naturally
occurring anti-DEA 7 antibodies. Seventy-one percent of samples were DEA 1
negative, 100% tested DEA 4-positive, and 95% tested DEA 7-negative. Suspected
anti-DEA7 antibodies were found in 32% dogs. The DEA 1 and 7-negative phenotypes
were significantly more common than in most canine populations. When a previously
tested Italian canine population was considered as blood donors for Corso dogs,
the risk of DEA 1 sensitisation using DEA 1 untyped blood was 29%, and of acute
haemolytic TRs after a second untyped DEA 1-incompatible transfusion was 8%. The
potential for delayed TRs between DEA 7-negative Corso dogs with suspected
naturally occurring anti-DEA 7 antibodies receiving untyped DEA 7-positive blood
was 11%. Conversely, when Corso dogs were blood donors for the same population,
the risk of DEA 1 sensitisation was 17% and the risk of an acute haemolytic TR
after a second DEA 1-incompatible blood transfusion was 3%. Corso dogs can be
suitable blood donors. Additional studies are needed to clarify whether the high
prevalence of naturally occurring anti-DEA 7 antibodies in this breed could
increase their risk of delayed TRs when they are blood recipients.
PMID- 28410672
TI - Effects of sedation and salbutamol administration on hyperpnoea and tidal
breathing spirometry in healthy horses.
AB - Sedation is often required to perform pulmonary function testing (PFT) in horses,
but drug effects may influence respiratory function. The current study was
designed to characterise the effects of sedation and bronchodilator
administration on absolute and relative indices of pulmonary function during
eupnoeic respiration and carbon dioxide-induced hyperpnoea (rebreathing) in
healthy horses using a pneumotachographic spirometry system. Sedation with
acetylpromazine (ACP), xylazine, or both drugs in combination was associated with
significant reductions in respiratory frequency, minute ventilation and peak
airflows during eupnoeic respiration. Peak expiratory airflow occurred later in
the respiratory cycle than was observed in untreated horses, and expiratory
relative flow-time indices were also affected during eupnoeic respiration.
Rebreathing attenuated the effects of sedation on indices of pulmonary function,
suggesting that future studies should consider the use of induced hyperpnoea as
part of the spirometry protocol. Based on the finding that all sedative agents
had some effect on eupnoeic respiration, albeit least pronounced with ACP, the
latter drug should be considered for sedation of horses undergoing PFT.
Salbutamol increased peak inspiratory flow during eupnoeic respiration in healthy
horses.
PMID- 28410673
TI - Hotspots of canine leptospirosis in the United States of America.
AB - Leptospirosis is a widespread zoonotic disease that causes hepatic and renal
disease in dogs and human beings. The incidence of leptospirosis in dogs in the
USA appears to be increasing. This study used 14 years of canine leptospirosis
testing data across 3109 counties in the USA to analyze environmental and socio
economic correlates with rates of infection and to produce a map of locations of
increased risk for canine leptospirosis. Boosted regression trees were used to
identify the probability of a dog testing positive for leptospirosis based on
microscopic agglutination test (MAT) results, and environmental and socio
economic data. The Midwest, East and Southwest were more likely to yield positive
tests for leptospirosis, although specific counties in Appalachia had some of the
highest predicted probabilities. Location (suburban areas or areas with deciduous
forest) and climate (precipitation and temperature) were predictors for positive
MAT results for leptospirosis, although the precise direction and strength of the
effects was difficult to interpret. Wide geographic variation in predicted risk
was identified. This risk mapping approach may provide opportunities for improved
diagnosis, control and prevention of leptospirosis in dogs.
PMID- 28410674
TI - The use of nosebands in equitation and the merits of an international equestrian
welfare and safety committee: A commentary.
PMID- 28410675
TI - The relationship between epileptiform discharges and background activity in the
visual analysis of electroencephalographic examinations in dogs with seizures of
different etiologies.
AB - Electroencephalographic (EEG) recordings in 125 outpatient dogs with various
epileptiform encephalopathies were acquired under medetomidine sedation using
subdermal wire electrodes. The features of canine EEG (background activity [BGA]
and epileptiform discharges [EDs]) were assessed, described and compared. The
dogs included neurologically healthy controls (N, n = 19), dogs with
portosystemic shunt (PSS, n = 9), dogs with intracranial pathologies (IP, n = 27)
and dogs with idiopathic epilepsy (IE, n = 70). A visual EEG analysis revealed
significantly more pronounced high voltage, low-frequency BGA in the PSS and IP
groups in comparison to the N and IE groups (PSS vs. N, PSS vs. IE P <0.0001; IP
vs. N, IP vs. IE P = 0.043). At least one ED in the recording was found in 47.37%
(n = 9/19) of the individuals in the N group, 88.9% (n = 8/9) of the dogs in the
PSS group, 77.78% (n = 21/27) of the dogs in the IP group and 61.43% (n = 43/70)
of the dogs in the IE group. The presence of bilateral symmetric triphasic (BST)
waves was significantly higher in the PSS group than in the remaining groups.
There was a strong prevalence of spike-waves in dogs with idiopathic epilepsy and
of BST waves in dogs with portosystemic shunt. None of the dogs in group N had
spike-waves or BST activity. EDs were observed more frequently in high and very
high voltage, low frequency BGA than in low voltage, high frequency BGA.
PMID- 28410676
TI - The immunoregulatory effects of co-infection with Fasciola hepatica: From bovine
tuberculosis to Johne's disease.
AB - Fasciola hepatica (liver fluke) is a parasite prevalent in much of the world that
causes the economically-important disease of fasciolosis in livestock. The threat
that this disease poses extends beyond its direct effects due to the parasite's
immunomodulatory effects. Research at this laboratory is focusing on whether this
immunoregulation can, in animals infected with liver fluke, exert a bystander
effect on concurrent infections in the host. It has already been established that
F. hepatica infection reduces cell mediated immune responses to Mycobacterium
bovis in cattle, and that the interaction between the two pathogens can be
detected on an epidemiological scale. This review explores the immunological
consequences of co-infection between F. hepatica and other bacterial infections.
Arguments are presented suggesting that immunity of cattle to Mycobacterium avium
subsp. paratuberculosis is also likely to be affected.
PMID- 28410677
TI - Challenges in calculation of the gamma index in radiotherapy - Towards good
practice.
AB - The gamma index (gamma) is one of the most commonly used metrics for the
verification of complex modulated radiotherapy. The mathematical definition of
the gamma is computationally expensive and various techniques have been reported
to speed up the calculation either by mathematically refining the gamma or
employing various computational techniques. These techniques can cause variation
in output with different software implementations. The gamma has traditionally
been used to compare a 2D measured plane against a 2D or 3D dose distribution.
Recently, software algorithm and hardware improvements have led to the
possibility of using measured 2D data from commercial detector arrays to
reconstruct a 3D-dose distribution and perform a volumetric comparison against
the treatment planning system (TPS). A limitation in this approach is that
commercial detector arrays have so far been limited by their spatial resolution
which may affect the accuracy of the reconstructed 3D volume and subsequently the
gamma calculation. Additionally, 3D versus 3D gamma comparison adds a layer of
complication in the calculation of the gamma given the increase in the number of
calculation points and the result cannot be as easily interpreted in the same way
as 2D comparison. This review summarises and highlights the computational
challenges of the gamma calculation and sheds light on some of these issues by
means of a bespoke MATLAB software to demonstrate the impact of interpolation,
gamma search distance, resolution and 2D and 3D calculations. Finally, a
recommendation is made on the minimum information that should be reported when
publishing gamma results.
PMID- 28410678
TI - Novel 6MV X-ray photoneutron detection and dosimetry of medical accelerators.
AB - PURPOSE: Dosimetry of fast, epithermal and thermal photoneutrons in 6MV X-ray
beams of two medical accelerators were studied by novel dosimetry methods.
METHODS: A Siemens ONCOR and an Elekta COMPACT medical accelerators were used.
Fast, epithermal and thermal photoneutron dose equivalents in 10cm*10cm 6MV X
rays fields were determined in air and on surface of a polyethylene phantom in X
and Y directions. Polycarbonate dosimeters as bare or with enriched 10B
convertors (with or without cadmium covers) were used applying a 50Hz-HV
electrochemical etching method. RESULTS: Fast, epithermal and thermal
photoneutron dose equivalents were efficiently determined respectively as
~1145.8, ~45.3 and ~170.6MUSv in air and ~1888.5, ~96.1 and ~640.6MUSv on phantom
per 100Gy X-rays at the isocenter of Siemens ONCOR accelerator in air. The dose
equivalent is maximum at the isocenter which decreases as distance from it
increases reaching a constant level. Tissue-to-air ratios are constants up to
15cm from the isocenter. No photoneutrons was detected in the Elekta COMPACT
accelerator. CONCLUSIONS: Fast, epithermal and thermal photoneutron dosimetry of
6MV X-rays were made by novel dosimetry methods in a Siemens ONCOR accelerator
with sum dose equivalent per Gy of ~0.0014% MUSv with ~0.21MeV mean energy at the
isocenter; i.e. ~150 times smaller than that of 18MV X-rays. This observation
assures clinical safety of 6MV X-rays in particular in single-mode machines like
Elekta COMPACT producing no photoneutrons due to no "beryllium exit window" in
the head structure.
PMID- 28410679
TI - Dual-energy imaging method to improve the image quality and the accuracy of dose
calculation for cone-beam computed tomography.
AB - PURPOSE: To improve the image quality and accuracy of dose calculation for cone
beam computed tomography (CT) images through implementation of a dual-energy cone
beam computed tomography method (DE-CBCT), and evaluate the improvement
quantitatively. METHODS: Two sets of CBCT projections were acquired using the X
ray volumetric imaging (XVI) system on a Synergy (Elekta, Stockholm, Sweden)
system with 120kV (high) and 70kV (low) X-rays, respectively. Then, the electron
density relative to water (relative electron density (RED)) of each voxel was
calculated using a projection-based dual-energy decomposition method. As a
comparison, single-energy cone-beam computed tomography (SE-CBCT) was used to
calculate RED with the Hounsfield unit-RED calibration curve generated by a CIRS
phantom scan with identical imaging parameters. The imaging dose was measured
with a dosimetry phantom. The image quality was evaluated quantitatively using a
Catphan 503 phantom with the evaluation indices of the reproducibility of the RED
values, high-contrast resolution (MTF50%), uniformity, and signal-to-noise ratio
(SNR). Dose calculation of two simulated volumetric-modulated arc therapy plans
using an Eclipse treatment-planning system (Varian Medical Systems, Palo Alto,
CA, USA) was performed on an Alderson Rando Head and Neck (H&N) phantom and a
Pelvis phantom. Fan-beam planning CT images for the H&N and Pelvis phantom were
set as the reference. A global three-dimensional gamma analysis was used to
compare dose distributions with the reference. The average gamma values for
targets and OAR were analyzed with paired t-tests between DE-CBCT and SE-CBCT.
RESULTS: In two scans (H&N scan and body scan), the imaging dose of DE-CBCT
increased by 1.0% and decreased by 1.3%. It had a better reproducibility of the
RED values (mean bias: 0.03 and 0.07) compared with SE-CBCT (mean bias: 0.13 and
0.16). It also improved the image uniformity (57.5% and 30.1%) and SNR (9.7% and
2.3%), but did not affect the MTF50%. Gamma analyses of the 3D dose distribution
with criteria of 1%/1mm showed a pass rate of 99.0-100% and 85.3-97.6% for DE
CBCT and 73.5-99.1% and 80.4-92.7% for SE-CBCT. The average gamma values were
reduced significantly by DE-CBCT (p< 0.05). Gamma index maps showed that matching
of the dose distribution between CBCT-based and reference was improved by DE
CBCT. CONCLUSIONS: DE-CBCT can achieve both better image quality and higher
accuracy of dose calculation, and could be applied to adaptive radiotherapy.
PMID- 28410680
TI - The evaluation of the neutron dose equivalent in the two-bend maze.
AB - The purpose of this study was to explore the effect of the second bend of the
maze, on the neutron dose equivalent, in the 15MV linear accelerator vault, with
two bend maze. These two bends of the maze were covered by 32 points where the
neutron dose equivalent was measured. There is one available method for
estimation of the neutron dose equivalent at the entrance door of the two bend
maze which was tested using the results of the measurements. The results of this
study show that the neutron equivalent dose at the door of the two bend maze was
reduced almost three orders of magnitude. The measured TVD in the first bend
(closer to the inner maze entrance) is about 5m. The measured TVD result is close
to the TVD values usually used in the proposed models for estimation of neutron
dose equivalent at the entrance door of the single bend maze. The results also
determined that the TVD in the second bend (next to the maze entrance door) is
significantly lower than the TVD values found in the first maze bend.
PMID- 28410681
TI - Simulation of scanner- and patient-specific low-dose CT imaging from existing CT
images.
AB - PURPOSE: Simulating low-dose Computed Tomography (CT) facilitates in-silico
studies into the required dose for a diagnostic task. Conventionally, low-dose CT
images are created by adding noise to the projection data. However, in practice
the raw data is often simply not available. This paper presents a new method for
simulating patient-specific, low-dose CT images without the need of the original
projection data. METHODS: The low-dose CT simulation method included the
following: (1) computation of a virtual sinogram from a high dose CT image
through a radon transform; (2) simulation of a 'reduced'-dose sinogram with
appropriate amounts of noise; (3) subtraction of the high-dose virtual sinogram
from the reduced-dose sinogram; (4) reconstruction of a noise volume via filtered
back-projection; (5) addition of the noise image to the original high-dose image.
The required scanner-specific parameters, such as the apodization window, bowtie
filter, the X-ray tube output parameter (reflecting the photon flux) and the
detector read-out noise, were retrieved from calibration images of a water
cylinder. The low-dose simulation method was evaluated by comparing the noise
characteristics in simulated images with experimentally acquired data. RESULTS:
The models used to recover the scanner-specific parameters fitted accurately to
the calibration data, and the values of the parameters were comparable to values
reported in literature. Finally, the simulated low-dose images accurately
reproduced the noise characteristics in experimentally acquired low-dose-volumes.
CONCLUSION: The developed methods truthfully simulate low-dose CT imaging for a
specific scanner and reconstruction using filtered backprojection. The scanner
specific parameters can be estimated from calibration data.
PMID- 28410682
TI - Integrated Digital Tomosynthesis for patient positioning of image-guided
radiation therapy.
AB - PURPOSE: Digital Tomosynthesis (DTS), originally developed for diagnostic
applications, has been recently introduced to image guided radiotherapy (IGRT).
Due to limited scan range, DTS was featured by anisotropic spatial resolution. A
new approach, integrated DTS (IDTS), was developed to improve image resolution of
DTS for patient positioning in IGRT. MATERIALS AND METHODS: For registration
purpose, both on-board IDTS (O-IDTS) and reference IDTS (R-IDTS) were required. O
IDTS was generated from cone-beam (CB) projections acquired in two narrow scan
ranges separated by 90 degrees . R-IDTS was generated from digitally
reconstructed radiographs (DRR) computed from planning CT in the same two narrow
scan ranges. Target offsets were determined by registration of O-IDTS and R-IDTS.
The reconstruction algorithms of DRR and IDTS were implemented on general purpose
graphics processing unit (GPGPU) for acceleration purpose. IDTS approach was
evaluated by phantom and patient cases. RESULTS: Comparing with DTS, IDTS
provided high-resolution images in both coronal view and sagittal views. The
image resolution of IDTS in axial view was significantly improved compared to
that of DTS, but still inferior compared to that of cone-beam computed tomography
(CBCT). Reconstruction accuracy and registration accuracy for all cases were high
which was within 1mm. Reconstruction performance of IDTS using general purpose
graphics processing unit (GPGPU) can be substantially improved, thus competent
for daily clinical use. CONCLUSIONS: IDTS can provide high-resolution images in
coronal and sagittal views with fewer CB projections. Image registration based on
IDTS was simple and reliable compared to DTS. IDTS is potentially a useful
imaging tool for fast patient positioning in IGRT.
PMID- 28410683
TI - Evaluation of automatic image quality assessment in chest CT - A human cadaver
study.
AB - PURPOSE: The evaluation of clinical image quality (IQ) is important to optimize
CT protocols and to keep patient doses as low as reasonably achievable.
Considering the significant amount of effort needed for human observer studies,
automatic IQ tools are a promising alternative. The purpose of this study was to
evaluate automatic IQ assessment in chest CT using Thiel embalmed cadavers.
METHODS: Chest CT's of Thiel embalmed cadavers were acquired at different
exposures. Clinical IQ was determined by performing a visual grading analysis.
Physical-technical IQ (noise, contrast-to-noise and contrast-detail) was assessed
in a Catphan phantom. Soft and sharp reconstructions were made with filtered back
projection and two strengths of iterative reconstruction. In addition to the
classical IQ metrics, an automatic algorithm was used to calculate image quality
scores (IQs). To be able to compare datasets reconstructed with different
kernels, the IQs values were normalized. RESULTS: Good correlations were found
between IQs and the measured physical-technical image quality: noise (rho=-1.00),
contrast-to-noise (rho=1.00) and contrast-detail (rho=0.96). The correlation
coefficients between IQs and the observed clinical image quality of soft and
sharp reconstructions were 0.88 and 0.93, respectively. CONCLUSIONS: The
automatic scoring algorithm is a promising tool for the evaluation of thoracic CT
scans in daily clinical practice. It allows monitoring of the image quality of a
chest protocol over time, without human intervention. Different reconstruction
kernels can be compared after normalization of the IQs.
PMID- 28410684
TI - Knowledge-based treatment planning: An inter-technique and inter-system
feasibility study for prostate cancer.
AB - PURPOSE: Helical Tomotherapy (HT) plans were used to create two RapidPlan
knowledge-based (KB) models to generate plans with different techniques and to
guide the optimization in a different treatment planning system for prostate
plans. Feasibility and performance of these models were evaluated. MATERIAL AND
METHODS: two sets of 35 low risk (LR) and 30 intermediate risk (IR) prostate
cancer cases who underwent HT treatments were selected to train RapidPlan models.
The KB predicted constraints were used to perform new 20KB plans using RapidArc
technique (KB-RA) (inter-technique validation), and to optimise 20 new HT (KB-HT)
plans in the Tomoplan (inter-system validation). For each validation modality, KB
plans were benchmarked with the manual plans created by an expert planner (EP).
RESULTS: RapidPlan was successfully configured using HT plans. The KB-RA plans
fulfilled the clinical dose-volume requirements in 100% and 92% of cases for
planning target volumes (PTVs) and organs at risk (OARs), respectively. For KB-HT
plans these percentages were found to be a bit lower: 90% for PTVs and 86% for
OARs. In comparison to EP plans, the KB-RA plans produced higher bladder doses
for both LR and IR, and higher rectum doses for LR. KB-HT and EP plans produced
similar results. CONCLUSION: RapidPlan can be trained to create models by using
plans of a different treatment modality. These models were suitable for
generating clinically acceptable plans for inter-technique and inter-system
applications. The use of KB models based on plans of consolidated technique could
be useful with a new treatment modality.
PMID- 28410685
TI - Evaluation of mesh- and binary-based contour propagation methods in 4D thoracic
radiotherapy treatments using patient 4D CT images.
AB - Based on four dimensional (4D) computed tomography (CT) images, mesh- and binary
based contour propagation algorithms for 4D thoracic radiotherapy treatments were
evaluated. Gross tumor volumes (GTVs), lungs, hearts and spinal cords on the CT
images at the end-exhale and end-inhale phases for six patients were delineated
by the physician. All volumes of interest (VOIs) were automatically propagated
from the end-exhale phase to the end-inhale phase using two propagation methods.
The propagated VOIs were quantitatively compared with the VOIs contoured at the
end-inhale phase by the physician using Dice Similarity Coefficient (DSC), Mean
Slicewise Hausdorff Distance (MSHD), Center Of Mass (COM) displacement and volume
difference. A two-sided Student's t test was implemented to examine the
significance of the differences between the results obtained from the two
algorithms. For GTVs, statistically significant differences between the two
algorithms were not observed. For all the other VOIs, the mesh-based method
showed higher mean DSCs for the heart, left lung, right lung and spinal cord,
lower mean MSHD for the spinal cord, lower mean COM displacement for the heart,
and lower mean volume differences for the left lung, right lung and spinal cord
with statistically significant differences than the binary-based method. The
running time for propagation was approximately 3s and 3min for the mesh- and
binary-based methods, respectively. Collectively, the mesh-based algorithm
provides superiorities in running time and reliability for contour propagation in
4D radiotherapy.
PMID- 28410686
TI - Relations between doses cumulated in bone marrow and dose delivery techniques
during radiation therapy of cervical and endometrial cancer.
AB - PURPOSE: To compare normal tissue complication probability (NTCP) and average
doses in the bone marrow (BM), obtained for five different radiotherapy delivery
and planning strategies of cervical and endometrial cancer. MATERIAL/METHODS: 50
patients were taken to analysis. For each case, 3 different dose delivery
techniques were used: 4-field, X15MV, 3DCRT; 7-field, X6MV, IMRT; and 2-arc,
X6MV, VMAT. Two optimization scenarios were used for the IMRT and VMAT plans
generation: with (+) and without (-) the inclusion of the BM as an optimized
structure. Average doses and dose-volume histogram parameters for the PTV, BM,
bladder, rectum, bowels and femoral heads were compared. In addition, the BM
doses were analyzed with respect to the PTV and/or volume of the BM, and NTCP for
the BM were computed. RESULTS: The dose in PTV for evaluated plans was similar.
The worst doses in organs at risk were obtained for 3DCRT. Using the BM during
the optimization of IMRT and VMAT reduces an average dose in BM without
increasing the doses in the bladder, rectum and bowels. Differences between doses
in BM for IMRT(+) and VMAT(+) plans were similar while NTCP was lower for
VMAT(+). A correlation between average dose in BM and the volume ratio of BM and
PTV was found for each technique. CONCLUSION: Using the BM during the
optimization of the IMRT and VMAT plans effectively reduces the dose in BM
without increasing the dose in the bladder, rectum and bowels. The VMAT(+) plans
were characterized by the lowest NTCP.
PMID- 28410687
TI - The evaluation of the feasibility of carotid sparing intensity modulated
radiation therapy technique for comprehensive breast irradiation.
AB - PURPOSE: To investigate the feasibility of carotid sparing intensity modulated
radiation therapy (CS-IMRT) to minimize the radiation dose to carotid arteries
for comprehensive irradiation of breast cancer patients who have risk factors for
atherosclerosis. The dose distribution of CS-IMRT technique and the conventional
irradiation technique were also compared. PATIENTS AND METHODS: Ten patients who
were previously treated with comprehensive three-dimensional conformal radiation
therapy (3DCRT) were selected. DICOM data were used to contour the carotid artery
and to create the virtual CS-IMRT plans for each patient. 3DCRT and CS-IMRT plans
were compared in terms of conformity index, homogeneity index, and the doses to
organ at risk and carotid arteries. RESULTS: The homogeneity and conformity
indices were better with CS-IMRT plans compared to 3DCRT plan. The homogeneity
index was 1.13 vs 1.11 (p=0.007) for 3DCRT and CS-IMRT and the conformity index
was 0.96 vs 0.97 (p=0.006) for 3DCRT and CS-IMRT. The radiation dose to the
carotid arteries were reduced by applying CS-IMRT without compromising the target
volume coverage. When the carotid artery was considered as organ at risk for CS
IMRT planning, the median of V50 was decreased to 0% from 12.5% compared to 3DCRT
plans (p=0.017). The median of the maximum dose to the carotid artery was
decreased under 50Gy with CS-IMRT. CONCLUSIONS: CS-IMRT can significantly reduce
the unnecessary radiation dose to the carotid arteries compared with conventional
3DCRT technique while maintaining target volume coverage. CS-IMRT technique can
be considered for breast cancer patient with high risk of atherosclerosis.
PMID- 28410688
TI - Education and training of medical physics in Iran: The past, the present and the
future.
AB - PURPOSE: The aim of this study was to investigate the current status of education
and training programs in medical physics in Iran. METHODS: A questionnaire was
designed and sent to 274 IAMP (Iranian Association of Medical Physicists) members
focusing on these two topics: the educational situation (course syllabus, number
of faculty members, number of PhD and MSc students and sub-fields offered in the
department) and the professional situation (work experience, workplaces of
medical physicists, postgraduate degrees that were granted and the amount of
therapy and imaging equipment). RESULTS: Medical physics education in Iran is
provided at 14 universities at master and doctorate levels. All medical physics
departments offer an MSc program and 6 of them offer a PhD program. Most medical
physics faculty (24%) work in the radiotherapy physics sub-specialty. Also, about
95 medical physics students graduate every year. There are six major peer
reviewed Iranian journals that publish medical physics papers in English. In
addition, there are 74 radiotherapy machines including Co-60 and LINACs (LINear
ACcelerators) across Iran as of 2013. CONCLUSIONS: The curriculum of medical
physics programs (MSc and PhD) in Iran must be improved to include long-term
clinical courses in the four major sub-specialties of radiotherapy, medical
imaging, nuclear medicine and radiation protection. It is hoped that clinical
medical physicists will go through nationally-accredited exams before assuming
independent clinical responsibilities. Moreover, the work situation of the
medical physics profession in Iran should be clear and the government authorities
must recognize importance of this interdisciplinary field in medicine.
PMID- 28410689
TI - Photoneutron depth dose equivalent distributions in high-energy X-ray medical
accelerators by a novel position-sensitive dosimeter.
AB - PURPOSE: The purpose of this study was to; (1) investigate employing a novel
position-sensitive mega-size polycarbonate (MSPC) dosimeter for photoneutron (PN)
depth, profile and dose equivalent distributions studies in a multilayer
polyethylene phantom in a Siemens ONCOR accelerator, and (2) develop depth dose
equivalent distribution matrix data at different depths and positions of the
phantom for patient PN dose equivalent determination and in particular for PN
secondary cancer risk estimation. METHODS: Position-sensitive MSPC dosimeters
were successfully exposed at 9 different depths of the phantom in a 10*10cm2 X
ray field. The dosimeters were processed in mega-size electrochemical chambers at
optimum conditions. Each MSPC dosimeter was placed at a known phantom depth for
PN depth dose equivalents and profiles on transverse, longitudinal and diagonal
axes and isodose equivalent distribution studies in and out of the X-ray beam.
RESULTS: PN dose equivalent distributions at any depth showed the highest value
at the beam central axis and decreases as the distance increases. PN dose
equivalent at any position studied in the axes has a maximum value on the phantom
surface which decreases as depth increases due to flux reduction by multi-elastic
scattering interactions. CONCLUSIONS: Extensive PN dose equivalent matrix data at
different depths and positions in the phantom were determined. The position
sensitive MSPC dosimeters proved to be highly efficient for PN depth, profile and
isodose equivalent distribution studies. The extensive data obtained highly
assists for determining PN dose equivalent of a patient undergoing high-energy X
ray therapy and for PN secondary cancer risk estimation.
PMID- 28410691
TI - Quantification of the uncertainties of a biological model and their impact on
variable RBE proton treatment plan optimization.
AB - PURPOSE: In proton radiation therapy, a relative biological effectiveness (RBE)
equal to 1.1 is currently assumed, although biological experiments show that it
is not constant. The purpose of this study was to quantify the uncertainties of a
published biological model and explore their impact on variable RBE treatment
plan (TP) optimization. METHODS: Two patient cases with a high and a low
(alpha/beta)x tumor were investigated. Firstly, intensity modulated proton
therapy TPs assuming constant RBE were derived, and subsequently the variable RBE
weighted dose (RWD), including the uncertainty originating in the fit to the
experimental data and the uncertainty of the (alpha/beta)x, were calculated.
Secondly, TPs optimized for uniform biological effect assuming a variable RBE
were created using the worst case tissue specific (alpha/beta)x. RESULTS: For the
nasopharyngeal cancer patient, the uncertainty of (alpha/beta)x corresponded to a
CTV D98 confidence interval (CI) of (-2, +4)% while for the fit parameter CI was
(-2,+1)%. For the standard fractionation prostate case the (alpha/beta)x CI was (
7,+5)% and the fit parameter CI was (-3,+3)%. For the hypofractionated case both
CIs were (-1,+1)%. In both patient cases, the RBE in most organs at risk (OARs)
was significantly underestimated by the constant RBE approximation, whereas the
situation was not as definite in the target volumes. Overdosage of OARs was
reduced by using the biological effect optimization. CONCLUSION: For the two
patient cases, the RWD uncertainty from the fit parameter in the biological model
contributed non-negligibly to the total uncertainty, depending on the patient
case and the organ. The presented optimization strategy is a basic method for
robust biological effect optimization to reduce potential consequences caused by
the (alpha/beta)x uncertainty.
PMID- 28410690
TI - Eye lens dose correlations with personal dose equivalent and patient exposure in
paediatric interventional cardiology performed with a fluoroscopic biplane
system.
AB - PURPOSE: To analyse the correlations between the eye lens dose estimates
performed with dosimeters placed next to the eyes of paediatric interventional
cardiologists working with a biplane system, the personal dose equivalent
measured on the thorax and the patient dose. METHODS: The eye lens dose was
estimated in terms of Hp(0.07) on a monthly basis, placing optically stimulated
luminescence dosimeters (OSLDs) on goggles. The Hp(0.07) personal dose equivalent
was measured over aprons with whole-body OSLDs. Data on patient dose as recorded
by the kerma-area product (PKA) were collected using an automatic dose management
system. The 2 paediatric cardiologists working in the facility were involved in
the study, and 222 interventions in a 1-year period were evaluated. The ceiling
suspended screen was often disregarded during interventions. RESULTS: The annual
eye lens doses estimated on goggles were 4.13+/-0.93 and 4.98+/-1.28mSv. Over the
aprons, the doses obtained were 10.83+/-0.99 and 11.97+/-1.44mSv. The correlation
between the goggles and the apron dose was R2=0.89, with a ratio of 0.38. The
correlation with the patient dose was R2=0.40, with a ratio of 1.79MUSvGy-1cm-2.
The dose per procedure obtained over the aprons was 102+/-16MUSv, and on goggles
40+/-9MUSv. The eye lens dose normalized to PKA was 2.21+/-0.58MUSvGy-1cm-2.
CONCLUSIONS: Measurements of personal dose equivalent over the paediatric
cardiologist's apron are useful to estimate eye lens dose levels if no radiation
protection devices are typically used.
PMID- 28410692
TI - Treatment outcome of extrapulmonary tuberculosis under Revised National
Tuberculosis Control Programme.
AB - BACKGROUND: Extrapulmonary tuberculosis (EPTB) constitutes 15-20% of tuberculosis
cases in India. Earlier studies have evaluated treatment outcomes of EPTB with
little information on outcomes of individual site of EPTB. AIMS: The objective
was to study the outcome of Directly Observed Treatment Short course (DOTS)
treatment of EPTB in different organ systems under Revised National Tuberculosis
Control Programme. METHODS: Multi-centric retrospectives record review was
carried out in three states in India. Data were collected from TB registers and
analysed. RESULTS: Of the total 2219 patients studied, there were more males in
age group 15-45. The commonest sites of EPTB were lymph node (34.4%) and pleural
effusion (25.2%) followed by abdominal (12.8%) and central nervous system (CNS)
(9.4%). Lymph node involvement was more common in females (58%) and pleural
effusion in males (70%). Overall treatment completion rate was 84% in EPTB
patients. Treatment completion was 86% in HIV negative EPTB patients compared to
66% in HIV positive patients. Individually, treatment completion rate observed as
follows: lymph node 90.9%, genitourinary 92.6%, bone and joint 86%, pleural
effusion 84.7%, abdominal 76% and CNS (tuberculoma and meningitis) 63.7%. The
site of EPTB was not recorded in 173 (7.8%) patients. CONCLUSION: Treatment
outcome of EPTB was poor in HIV infected patients and those with CNS
tuberculosis. More efforts are needed to improve the treatment completion rates
in these groups of patients.
PMID- 28410693
TI - Clinical and radiological spectrum of intracranial tuberculosis: A hospital based
study in Northeast India.
AB - : Central nervous system tuberculosis (TB) is the most severe extra pulmonary TB
having a high mortality and morbidity. OBJECTIVE: To study the various clinical,
biochemical, and radiological spectrum of intracranial TB. MATERIALS AND METHOD:
Ninety-three patients were enrolled in this prospective study after ethical
clearance and consent from August 2013 to May 2015. The entire clinical course
with complications and predictors of mortality were assessed. RESULTS: 36 females
(38.7%) and 57 males (61.3%) were included whose mean age of presentation was
32.3+/-17.05 years. Alcohol was the most common risk factor seen in 19.4%.
Headache (90.3%) was the most common symptom. Co-infection with human
immunodeficiency virus, cryptococcal, and toxoplasmosis were seen in 11, 3, and 2
patients, respectively. Cerebrospinal fluid analysis showed acid-fast bacilli in
1 patient; polymerase chain reaction for TB and BACTEC was positive in one and
three patients, respectively. Neuroimaging showed basal exudates (21.7%),
tuberculoma (28.6%), brain edema (27%), hydrocephalus (32.9%), infarct (21%), and
abscess (2.9%). Complications were noted such as brain edema (24.7%), vasculitis
(26.9%), hydrocephalus (17.2%), hyponatremia (11.8%), drug-induced hepatitis
(4.3%), and drug rash in 5 patients (5.4%). A total of 25 patients (26.9%) died
and 38 patients (40.9%) developed neurological sequelae like hemiparesis,
paraparesis, visual loss, and hearing loss. Logistic regression showed that a
Glasgow scale of <10, British Medical Research Council stage 3, and vasculitis
were associated with poor outcome. CONCLUSION: Lack of sensitive diagnostic
method and criteria makes central nervous system TB a challenge where early
diagnosis and prompt management is required.
PMID- 28410694
TI - Pyridines: Multidrug-resistant tuberculosis (MDR-TB) inhibitors.
AB - Mycobacterium tuberculosis (MTB) infection has become an increasing health threat
due to the worldwide emergence of multidrug-resistant MTB (MDR-MTB) strain.
Isoniazid (pyridine) resistance problem is a complex process and is associated
with mutations in several genes. However, the emergence of isoniazid (INH)
resistant M. tuberculosis strains dictates the necessity for redesigning this old
drug in order to create analogs effective against INH-resistant strains by using
rational approach. In light of these findings, the present review discusses the
synthesis, structural optimization, and modification in pyridine structure to
combat the problem of multidrug-resistant tuberculosis.
PMID- 28410695
TI - Linezolid-induced optic neuropathy in XDR pulmonary TB: A case series.
AB - Optic neuropathy has been reported as a side effect of long-term use of
linezolid. This is particularly seen in cases of extensively drug resistant
tuberculosis (XDR-TB) where treatment with linezolid may continue for about 24-30
months. We, hereby, report two cases of XDR-TB treated patients with a regimen
containing linezolid who developed progressive painless loss of vision during the
course of treatment. In both the cases, the visual symptoms resolved completely
on withdrawing linezolid. Early recognition of this rare side effect and timely
withdrawal may salvage the eyesight of such patients.
PMID- 28410696
TI - Isolated splenic tuberculosis diagnosed by endoscopic ultrasound-guided fine
needle aspiration.
AB - Our patient was a 48-year-old female, who presented with history of persistent
low-grade fever and weight loss. The CT scan of the abdomen revealed multiple
hypodense lesions in spleen. No primary focus of infection was detected in any
other organs. Endoscopic ultrasound-guided fine needle aspiration of splenic
lesion revealed granulomatous inflammation. The patient was started on anti
tuberculous therapy. There is a diagnostic possibility of splenic tuberculosis
even in immunocompetent individuals and we chose a combination anti-tuberculous
therapy as the first line treatment with consideration of splenectomy depending
on the response.
PMID- 28410697
TI - Multifocal pure tubercular osteomyelitis: An unusual presentation in childhood.
AB - Tuberculosis is a major health problem in the developing world. One-third of
children infected with Mycobacterium tuberculosis have extra pulmonary
involvement. Skeletal tuberculosis occurs in 1-6% of them with vertebra being the
commonest site. Pure tubercular osteomyelitis without joint involvement occurs in
only 2-3% cases of osteoarticular tuberculosis. Common sites are femur, tibia,
and fibula. Disseminated skeletal involvement is very rare in children (7%) and
calvarial osteomyelitis is even rarer (1%). Here, we report a unique case of
disseminated skeletal TB. A 7-year-old tribal girl with no evidence of
immunodeficiency presented with multiple lytic lesions involving skull, sternum,
and hip bone surprisingly sparing the joints and appendicular skeleton. There was
no pulmonary involvement either. FNAC from all three swellings showed presence of
acid-fast bacillus. Bone biopsy followed by culture in BACTEC further confirmed
the diagnosis. There was complete resolution of the swellings after one year of
anti-tubercular drug therapy.
PMID- 28410698
TI - Spontaneous chylothorax revealing a mediastinal and abdominal lymph node
tuberculosis.
AB - Chylothorax is a rare manifestation of tuberculosis. We report a case of
spontaneous chylothorax due to tuberculosis. A 62-year-old woman was admitted
with fever, chest pain and dyspnea. Chest and abdominal computed tomography
revealed a fluid collection with necrotic mediastinal and abdominal lymph nodes.
Biopsy of lymph nodes by mediastinoscopy. The patient was treated with anti
tuberculosis medication. He is clinically improved and his pleural effusion also
completely resolved.
PMID- 28410699
TI - Anaphylaxis to rifampicin and pyrazinamide in a child with tuberculous
meningitis: A case report.
AB - Rifampicin (RFP) and pyrazinamide (PZA) are the primary anti-tubercular drugs
with a considerably safe profile. However, none of the drugs are without adverse
reactions. They both can lead to a variety of adverse effects including life
threatening anaphylaxis. We report an interesting and possibly the first case of
concurrent hypersensitivity to two primary anti-tubercular treatment (ATT) drugs.
Hypersensitivity to RFP and PZA was confirmed in this patient by drug provocation
and intradermal skin testing. He improved on alternative ATT regime withdrawing
RFP and PZA.
PMID- 28410701
TI - LAMP - An innovative POC tool for diagnosing pulmonary TB in remote areas.
PMID- 28410700
TI - GeneXpert: A momentous innovation that needs a touch of prudence.
PMID- 28410702
TI - Study of the structure and functioning of referral mechanism of patients
receiving treatment and records linkage under Revised National Tuberculosis
Control Programme (RNTCP) of Government of India.
AB - BACKGROUND: The reliable and successful performance of the Revised National
Tuberculosis Control Programme (RNTCP) "referral mechanism" is profoundly
important in the medical college scenario, and it is an important requirement of
the programme to have feedback status report of the referred patients. METHODS:
An observational study on tuberculosis (TB) patients referred from Directly
Observed Treatment (DOT) Centre, Sri Venkateswara Institute of Medical Sciences
(SVIMS) was conducted during the years 2010 to 2012 (n=622). Subjects referred to
other TUs within the District but failed to report there within 45 days
constituted "cases" and subjects, who obtained treatment from the TUs they were
referred to "controls". The initial information or confirmation of registration
for treatment status feedback were obtained from patient/Senior Treatment
Supervisor (STS)/District Tuberculosis Centre (DTC) levels respectively both
before using intervention (Phase I, year 2010) and after using intervention
(Phase II, years 2011 and 2012) by sending day-to-day text messaging of referral
details of patients to the STS and District Tuberculosis Officer (DTO). RESULTS:
During Phase I, the distribution of subjects (n=242) in the ages <=25, 26-50, and
>=51 years was similar in both the cases and control subjects (p=0.054). Further,
there was no statistically significant difference in the median age of the cases
and controls [34.5 (interquartile range, IQR 31-51) vs 39 (30-54); p=0.319].
There was no statistically significant difference in other parameters, such as
gender distribution (p=0.9748); availability of phone numbers (p=0.9614); type of
disease (p=0.8395); and type of case (p=0.0793). In Phase II, the effect of
intervention on feedback related parameters showed statistically significant
improvement in all the parameters such as initial feedback levels obtained within
15 days (p=0.0077); within 45 days (p<0.0001); above 45 days (p<0.0001);
registration status confirmation within 45 days (p=0.0343); mismatch of feedback
received by observer (p<0.0001); and telephone number of patients recorded
(p<0.0001). CONCLUSION: Our findings suggest that text messaging reminders may be
an important tool to achieve optimal feedback response in resource-limited
settings.
PMID- 28410703
TI - Frequency and outcomes of new patients with pulmonary tuberculosis in Hatay
province after Syrian civil war.
AB - OBJECTIVE: It is known that tuberculosis is frequently seen among refugees. Hatay
province is one of the cities that substantially expose to migration of refugees
after Syrian civil war. In this study, it was aimed to compare frequency of new
pulmonary tuberculosis (PTB) cases and treatment success/cure rates between
Turkish and Syrian patients. FINDINGS: The study included 211 patients with PTB
(178 Turkish and 33 Syrian patients) registered to Hatay Tuberculosis Outpatient
Clinic between 2010 and 2013. On the basis of years, number of PTB patients
registered was 53 (Turkish/Syrian: 52/1) in 2010, 44 (44/0) in 2011, 41 (39/2) in
2012, and 73 (43/30) in 2013. There were no significant differences between
Turkish and Syrian patients regarding age groups, gender, marital status, contact
history, smear result, and drug sensitivity assays when treatment success was
considered (p>0.05). Directly observed therapy (DOT) rate was higher in patients
who achieved successful treatment (97.6% vs. 2.4%; p<0.001). Number of patients
successfully treated was smaller among Syrian patients (63.6% vs. 88.8%;
p<0.001). Leaving the treatment and/or transfer rates were higher among Syrian
patients (30.3% vs. 3.9%; p<0.001). During the study period, drug-resistant
tuberculosis was detected in one Syrian and 3 Turkish patients. CONCLUSIONS:
Although PTB frequency has increased in Hatay province within prior 4 years,
treatment success among local population is still within limits established by
World Health Organization (WHO). However, the treatment goal could not be
achieved when considered together with refugees. To improve treatment success in
refugees, implementation of a new national tuberculosis is needed control program
in this population.
PMID- 28410704
TI - Resident doctors' attitudes toward tuberculosis patients.
AB - BACKGROUND: The attitude of the resident doctors toward tuberculosis (TB)
patients can affect their treatment seeking behavior, compliance to treatment as
well as reinforce the stigma attached to the disease by the society at large.
AIMS: To assess the attitudes of resident medical doctors toward TB patients.
MATERIAL AND METHODS: A cross-sectional study was conducted among postgraduate
resident medical doctors at B.J. Government Medical College and Sassoon General
Hospital, Pune in September 2014. The background characteristics and attitudes
were assessed using a semi-structured questionnaire. The responses were analyzed
using Chi-square/Fishers exact test and calculating odds ratio (OR). RESULTS: Of
the 212 resident doctors who responded to the question on attitudes, 132 (62%)
see TB patients on a daily basis, 40 (19%) of the resident doctors had attended a
training program on TB, and 99 (47%) respondents knew of a colleague with TB.
Only 104 (49%) of the residents reported feeling compassion for and the desire to
help TB patients. The residents who had attended a training program in TB were
three times more likely to report compassion and a desire to help TB patients
than those who had not undergone such training [28/40 vs 76/172; p=0.005;
OR=2.95, 95% CI (1.33-6.61)]. Compared to residents who did not know of a
colleague with TB, residents who knew of a colleague with TB were nearly three
times more likely to avoid managing TB patients or fear them and think they may
cause infection [33/99 vs 17/113; p=0.002; OR=2.82, 95% CI (1.39-5.76)].
CONCLUSION: The feeling of fear, lack of compassion, and tendency to avoid TB
patients reported by 51% of the patients is a cause of concern. Addressing the
knowledge gaps through training programs and ensuring safe working environment
will make residents more supportive and compassionate toward TB patients which
will contribute to TB control.
PMID- 28410705
TI - Patients' perception towards directly observed treatment - A qualitative study
from Kollam district, Kerala, southern India.
AB - BACKGROUND: The Direct Observation of Treatment (DOT) is an important component
of the country's TB Control strategy. Standards of TB care in India and the End
TB strategy emphasised the importance of a patient-centered approach to foster
adherence. A qualitative study was conducted to explore the perception of people
with Tuberculosis in Kerala regarding DOT, mechanisms to make the treatment of TB
more patients centered and to identify the preferable mechanisms to ensure
adherence. METHODS: Six focus group discussions were conducted - two among people
with TB from rural area, two among people with TB in urban area, one among
multipurpose health workers of rural area and one among key field staff of TB
control in urban area. RESULTS: Patients who were on a strict DOT were unhappy
about the issues of confidentiality, patient inconvenience and provider centered
approach. A flexible, patient centered approach were a family member can act as
the DOT provider with guidance from a trained health worker was evolved as the
most acceptable and comfortable mode of treatment to majority of the TB patients.
They felt that a strict external monitor as a DOT provider was not a necessity in
majority of the cases. Only practical way to effectively incorporate ICT in
monitoring patient compliance in current scenario was identified as daily phone
call reminders. Patients also expressed their concerns in keeping the medicines
for entire duration at home. CONCLUSION: A flexible patient wise individualized
system based on patient's behavior, literacy and awareness along with attitude of
family members is needed to ensure adherence to anti TB drugs.
PMID- 28410706
TI - Conventional TBNA experience over a 10-year period: Diagnostic yield and
associated limitations in a tertiary care government set-up.
AB - INTRODUCTION: It is challenging for pulmonologists to sample mediastinal lymph
nodes or some endobronchial lesions because of safety concerns. C-TBNA
(conventional transbronchial needle aspiration) is a procedure to sample such
sites, but is underutilized. We present a retrospective review of patients
subjected to C-TBNA through fibre-optic bronchoscopy over a 10-year period.
MATERIALS AND METHODS: Year-wise statistics of C-TBNA was reviewed and results
were analyzed with regard to sampling sites and type of intraluminal lesions
encountered, diagnosis made and their correlation with sampling sites, sex and
age. RESULTS: 160 patients underwent successful C-TBNA with 111/160 (69.4%) males
and 49/160 (30.6%) females. Non-availability of in-house needles dramatically
decreased the number of procedures. 17 (10.6%) patients underwent C-TBNA from
intraluminal bulge, 41 (25.6%) from endobronchial growth and 102 (63.8%) from
enlarged lymph nodes. Subcarinal lymph node alone was predominantly aspirated in
83/102 (81.4%) lymph node sampled patients. In 100 (62.5%) patients, diagnosis
was achieved as follows: 57/100 as tumour, 30/100 as infection and 13/100 as
sarcoidosis. Non-small cell lung cancer (NSCLC) and tuberculosis (TB)
predominated in tumour and infection groups, respectively. Patients with
intraluminal growth or bulge had higher chances of being diagnosed with tumour
(p<0.001). Intraluminal bulge and growth predominated in older ages while
enlarged lymph nodes predominated in the young (p=0.018). Infection was
predominantly diagnosed in younger patients, sarcoidosis in the middle aged, and
tumour in older patients (p<0.001). CONCLUSION: C-TBNA should be used as a
diagnostic tool in developing countries like India. It can give confirmatory
results in difficult cases with intraluminal growths and submucosal lesions. Cost
constraints are of paramount importance, and hence continuous supply of expensive
accessories should be ensured.
PMID- 28410707
TI - Capsulorhexis: The perfect circle.
PMID- 28410708
TI - Twenty-nine-gauge dual-chandelier retroillumination for the non-open-sky
continuous curvilinear capsulorhexis in the penetrating keratoplasty triple
procedure.
AB - We describe a technique for the penetrating keratoplasty (PKP) triple procedure
that uses 29-gauge dual-chandelier illumination during creation of a non-open-sky
continuous curvilinear capsulorhexis (CCC). The chandeliers are inserted through
the pars plana into the vitreous cavity through the bulbar conjunctiva at the 3
o'clock and 9 o'clock positions. We compared this approach with that of a core
vitrectomy, in which a single 25-gauge port is inserted into the vitreous cavity
transconjunctivally through the upper temporal pars plana. The area of halation
around the corneal opacity was significantly smaller in the 29-gauge group than
in the 25-gauge group. The reduction in halation improved visibility of the
anterior capsule and enabled the surgeon to perform CCC with greater safety. The
29-gauge chandelier system was more suitable than the 25-gauge chandelier system
for the non-open-sky CCC component of the PKP triple procedure.
PMID- 28410709
TI - Suture-guided sulcus implantation of a single-piece foldable acrylic intraocular
lens after posterior capsule rupture.
AB - We describe a technique for suture-guided sulcus implantation of a foldable
acrylic posterior chamber IOL (PC IOL). A 10-0 monofilament nylon suture is used
to control insertion of the PC IOL over the ciliary sulcus and enable safe
retrieval if the PC IOL drops during insertion, stabilization, or centration. In
this technique, the 10-0 monofilament nylon suture acts as a guy rope to hold
onto the PC IOL, enabling the surgeon to inject the IOL into the sulcus, unfold
it in the iris plane, dial it in the appropriate meridian, and stabilize it.
PMID- 28410710
TI - Supracapsular glued intraocular lens in progressive subluxated cataracts:
Technique to retain an intact vitreous face.
AB - We describe a technique to prevent late intraocular lens (IOL) subluxation and
dislocation that can be associated with progressive zonulopathy. Supracapsular
glued IOL fixation is done to retain an intact anterior hyaloid face and avoid
vitreous disturbance while providing stable long-term IOL fixation.
Phacoemulsification is followed by glued IOL implantation above intact anterior
and posterior capsules. Sclerotomies are created ab interno in a supracapsular
plane under diametrically opposite lamellar scleral flaps without entering the
vitreous cavity. Haptics are externalized in the supracapsular plane and tucked
into intrascleral tunnels. Intraoperative or postoperative posterior
capsulorhexis or capsulotomy and anterior capsule relaxing cuts can prevent
capsule phimosis.
PMID- 28410711
TI - Failure Modes and Effects Analysis of bilateral same-day cataract surgery.
AB - PURPOSE: To systematically analyze potential process failures related to
bilateral same-day cataract surgery toward the goal of improving patient safety.
SETTING: Twenty-one Kaiser Permanente surgery centers, Northern California, USA.
DESIGN: Retrospective cohort study. METHODS: Quality experts performed a Failure
Modes and Effects Analysis (FMEA) that included an evaluation of sterile
processing, pharmaceuticals, perioperative clinic and surgical center visits, and
biometry. Potential failures in human factors and communication (modes) were
identified. Rates of endophthalmitis, toxic anterior segment syndrome (TASS), and
unintended intraocular lens (IOL) implantation were assessed in eyes having
bilateral same-day surgery from 2010 through 2014. RESULTS: The study comprised
4754 eyes. The analysis identified 15 significant potential failure modes. These
included lapses in instrument processing and compounding errors of intracameral
antibiotics that could lead to endophthalmitis or TASS, and ambiguous
documentation of IOL selection by surgeons, which could lead to unintended IOL
implantation. Of the study sample, 1 eye developed endophthalmitis, 1 eye had
unintended IOL implantation (rates, 2 per 10 000; 95% confidence interval [CI],
0.1-12.0 per 10 000), and no eyes developed TASS (upper 95% CI, 8 per 10 000).
Recommendations included improving oversight of cleaning and sterilization
practices, separating lots of compounded drugs for each eye, and enhancing IOL
verification procedures. CONCLUSIONS: Potential failure modes and recommended
actions in bilateral same-day cataract surgery were determined using an FMEA.
These findings might help improve the reliability and safety of bilateral same
day cataract surgery based on current evidence and standards.
PMID- 28410712
TI - Swept-source optical coherence tomography to screen for macular pathology in eyes
having routine cataract surgery.
AB - PURPOSE: To determine the incremental benefit of swept-source optical coherence
tomography (SS-OCT) in identifying occult macular disease preoperatively in
patients scheduled for routine cataract surgery. SETTING: Shahzad Eye Hospital,
Karachi, Pakistan. DESIGN: Prospective case series. METHODS: Preoperative SS-OCT
scans were performed in all patients scheduled to have cataract surgery between
January and March 2016. Scans were subsequently reviewed for the presence of
macular abnormalities. Patients with clinically detectable retinal pathologies
were excluded. RESULTS: Of the 179 eligible patients, 155 were included in the
study. Macular pathology was noted in 17 patients (10.9%). The most commonly
identified conditions were age-related macular degeneration (n = 5), idiopathic
epiretinal membrane (n = 4), and vitreomacular interface abnormalities (n = 4).
Other abnormalities included cystoid macular edema (n = 2) and ellipsoid zone
abnormalities (n = 2). Media opacities precluded interpretation of 9 scans
(4.7%). CONCLUSIONS: Swept-source OCT was an effective noninvasive modality for
detecting macular structural abnormalities, especially in the presence media
opacities. Optical coherence tomography imaging should be considered as an
adjunct to routine dilated fundus examination for macular evaluation,
particularly if premium intraocular lenses are being considered.
PMID- 28410713
TI - Axial length measurements: Comparison of a new swept-source optical coherence
tomography-based biometer and partial coherence interferometry in myopia.
AB - PURPOSE: To compare axial length (AL) measurements between a swept-source optical
coherence tomography (SS-OCT) biometer (IOLMaster 700) and a partial coherence
interferometry (PCI) biometer (IOLMaster, version 5.4) in myopic eyes. SETTING:
Severance Hospital, Yonsei University, Seoul, South Korea. DESIGN: Prospective
evaluation of a diagnostic test. METHODS: This study enrolled patients with a
diagnosis of myopia in their medical records. Two consecutive AL measurements
were performed in each eye in random order using the 2 biometers. Subanalysis was
performed according to lens status, fixation status, degree of myopia, and the
presence of posterior staphyloma. The interdevice agreement was evaluated with
Bland-Altman analyses and paired t tests. RESULTS: This study comprised 219 eyes
of 117 patients. During a fixation check using SS-OCT, 19.6% of eyes showed
fixation loss. Overall, the SS-OCT biometer showed a longer AL than the PCI
biometer. (P < .001) In a subanalysis that categorized eyes according to lens
status, fixation status, degree of myopia, and the presence of posterior
staphyloma, the SS-OCT biometer also showed longer ALs than the PCI biometer. Of
eyes with good fixation, significant differences in AL measurements between
devices were detected for those with posterior staphyloma (P < .001) but not for
those without posterior staphyloma (P = .104). CONCLUSIONS: The 2 devices showed
differences in AL measurements in myopic eyes. Fixation status and the presence
of posterior staphyloma were important factors in these differences. For myopic
eyes with posterior staphyloma, the SS-OCT biometer is expected to produce more
precise AL measurements because it allows evaluation of the fixation status.
PMID- 28410714
TI - Accuracy of 3 new methods for intraocular lens power selection.
AB - PURPOSE: To evaluate the accuracy of 3 new methods for intraocular lens (IOL)
power selection (Hill-Radial Basis Function [Hill-RBF] method, FullMonte method,
and the Ladas Super Formula) compared with that of the Holladay 1 and Barrett
Universal II formulas. SETTING: Ophthalmology Department, Alfred Hospital,
Melbourne, Australia. DESIGN: Retrospective case series. METHODS: Patients who
had uneventful cataract surgery with insertion of the Acrysof IQ SN60WF IOL over
5 years were included in the study. Data obtained from the electronic medical
record and the IOLMaster device were entered into the respective calculators
using self-designed computer programs. Using optimized lens constants, the
predicted refractive outcome using each of the 5 methods/formulas was calculated
and compared with the actual refractive outcome to give the prediction error.
Eyes were separated into subgroups based on axial length as follows: short
(<=22.0 mm), medium (>22.0 to <24.5 mm), medium-long (>=24.5 to <26.0 mm), and
long (>=26.0 mm). RESULTS: The study comprised 3122 eyes of 3122 patients. A
statistically significant difference in the mean absolute prediction error (MAE)
between the 5 methods for IOL power calculation was found (P < .001), with the
Barrett Universal II formula being the most accurate. The Ladas Super Formula had
the third lowest MAE, the Hill-RBF the fourth lowest MAE, and the FullMonte the
highest MAE of the 5 methods assessed. CONCLUSION: New methods for predicting the
postoperative refraction failed to yield more accurate results than current
formulas.
PMID- 28410715
TI - Comparison of astigmatic prediction errors associated with new calculation
methods for toric intraocular lenses.
AB - PURPOSE: To compare the prediction errors in residual astigmatism associated with
new calculation methods for toric intraocular lenses (IOLs). SETTING: Hospital da
Luz, Lisbon, Portugal. DESIGN: Retrospective case series. METHODS: In eyes having
cataract surgery with toric IOL implantation (Acrysof IQ), the predicted residual
astigmatism by each calculation method was compared with the manifest refractive
astigmatism. The prediction error in residual astigmatism was calculated by
vector analysis. RESULTS: The study evaluated 86 eyes (86 patients). All
calculation methods resulted in overcorrection of with-the-rule astigmatism and
undercorrection of against-the-rule astigmatism. For the original Alcon
calculator, the centroid prediction error was 0.43 @ 170, which was reduced by
the application of the Baylor nomogram (0.35 @ 169) or the Abulafia-Koch formula
(0.34 @ 170). For the Holladay toric calculator, the centroid prediction error
was 0.40 @ 168, which was reduced by the Baylor nomogram (0.35 @ 169), the
Abulafia-Koch formula (0.25 @ 158), and the Goggin coefficient of adjustment
(0.38 @ 170). The Barrett calculator and the newly introduced Alcon calculator
yielded the lowest centroid prediction errors (0.17 @ 165 and 0.19 @ 164,
respectively). The centroid prediction error of ray-tracing calculations
(PhacoOptics) using real posterior corneal surface measurements was 0.32 @ 171.
CONCLUSIONS: The Barrett toric calculator and the new Alcon calculator yielded
the lowest astigmatic prediction errors. Of the nomogram methods, application of
the Abulafia-Koch formula achieved the best results. The outcomes of toric IOL
implantation might be improved by using 1 of these calculation methods.
PMID- 28410716
TI - Clinical performance in continuous curvilinear capsulorhexis creation supported
by a digital image guidance system.
AB - PURPOSE: To test whether a default capsulorhexis diameter could be attained more
precisely when manual continuous curvilinear capsulorhexis (CCC) creation was
supported by a biomorphological detection unit. SETTING: Ruhr University Eye
Hospital, Bochum, Germany. DESIGN: Prospective interventional study. METHODS:
Patients were assigned to either of 2 groups. In the first group, a digital image
system was applied to guide capsulorhexis. In the second group, the CCC was
created without digital support. Postoperatively, horizontal and vertical
capsulorhexis dimensions were measured. A set target diameter of 5.5 mm was
compared with intraoperative and postoperative CCC diameters, which were also
compared with each other. The number of eyes with postoperative CCC diameters
outside the reference range of 4.5 to 6.0 mm was assessed. RESULTS: In 427 eyes,
the capsulorhexis size was assessed. Digital image guidance was applied in 203
eyes. Intraoperatively, horizontal capsulorhexis diameters created with surgical
guidance differed significantly less from the target diameter than in the control
group (P < .001). Eyes treated with surgical guidance differed significantly less
from the target diameter (P < .001). Analogously, vertical capsulorhexis
diameters differed significantly less from the target when digital support was
used, intraoperatively and postoperatively (P < .001). In 418 eyes, postoperative
diameters were significantly larger than intraoperatively in both directions (P <
.001). Vertical CCC diameters were more frequently within the reference range
intraoperatively and postoperatively with surgical guidance (P = .009).
Horizontally, eye tracking showed accordance with the target diameter in 87.6%
(controls: 91.7%). CONCLUSION: Intraoperative image guidance facilitated CCC
creation significantly during standard phacoemulsification.
PMID- 28410717
TI - Greater vertical spot spacing to improve femtosecond laser capsulotomy quality.
AB - PURPOSE: To evaluate the effect of adapted capsulotomy laser settings on the
cutting quality in femtosecond laser-assisted cataract surgery. SETTING: Ruhr
University Eye Clinic, Bochum, Germany. DESIGN: Prospective randomized case
series. METHODS: Eyes were treated with 1 of 2 laser settings. In Group 1, the
regular standard settings were used (incisional depth 600 MUm, pulse energy 4
MUJ, horizontal spot spacing 5 MUm, vertical spot spacing 10 MUm, treatment time
1.2 seconds). In Group 2, vertical spot spacing was increased to 15 MUm and the
treatment time was 1.0 seconds. Light microscopy was used to evaluate the cut
quality of the capsule edge. The size and number of tags (misplaced laser spots,
which form a second cut of the capsule with high tear risk) were evaluated in a
blinded manner. Groups were compared using the Mann-Whitney U test. RESULTS: The
study comprised 100 eyes (50 eyes in each group). Cataract surgery was
successfully completed in all eyes, and no anterior capsule tear occurred during
the treatment. Histologically, significant fewer tags were observed with the new
capsulotomy laser setting. The mean score for the number and size of free tags
was significantly lower in this group than with the standard settings (P < .001).
CONCLUSIONS: The new laser settings improved cut quality and reduced the number
of tags. The modification has the potential to reduce the risk for radial capsule
tears in femtosecond laser-assisted cataract surgery. With the new settings, no
tags and no capsule tears were observed under the operating microscope in any
eye.
PMID- 28410718
TI - Analysis of competency in phacoemulsification trainees using the cumulative sum
analysis.
AB - PURPOSE: To determine the number of cases required to achieve competency in
phacoemulsification in terms of the posterior capsule rupture rate. SETTING:
Singapore National Eye Centre, Singapore. DESIGN: Retrospective cohort study.
METHODS: The posterior capsule rupture rate of the first 300 phacoemulsification
cases performed by each trainee in the Singapore National Eye Centre (2004 to
2012) was charted using cumulative sum graphs. Competency was primarily defined
as a posterior capsule rupture rate of 2% or lower and secondarily as 5% or
lower. RESULTS: Twenty trainees fulfilled the inclusion criteria. Four trainees
(20%) and 19 trainees (95%) achieved a posterior capsule rupture rate of 2% and
5%, respectively. At least 41 cases were required to achieve a 5% posterior
capsule rupture rate (mean 106, median 83). CONCLUSIONS: There was considerable
variation in the trainees' abilities. Only 20% of the trainees achieved a
posterior capsule rupture rate of 2% or lower and required at least 212 cases.
PMID- 28410719
TI - Assessment of resident training and preparedness for cataract surgery.
AB - PURPOSE: To assess which surgical teaching methods are used for residency
surgical training and which methods residents find most useful. SETTING: Wilmer
Eye Institute, Baltimore, Maryland, USA. DESIGN: Retrospective observational
cross-sectional study. METHODS: A survey was developed and sent to residents at
accredited ophthalmology training programs in the United States. The survey asked
about demographics, program characteristics, surgical training methods, perceived
initial preparedness, eventual competence, and difficulty with the steps of
cataract surgery. The correlation between surgical training methods was compared
with perceived preparedness, competence, and difficulty. RESULTS: One hundred
sixteen residents completed the survey. Discussing surgical procedures with
senior surgeons or using surgical simulators preoperatively improved resident
perceived surgical competency in several areas, such as paracentesis. Residents
who had preoperative discussions with senior surgeons were statistically less
likely to report difficulty with surgical procedures, such as performing a clear
corneal incision. The presence of a supervised wet lab or surgical simulator in a
residency was also associated with improved resident-perceived surgical
competency. CONCLUSION: Educational resources, such as surgical simulators and
supervised wet labs, tended to be associated with greater resident-perceived
competency for steps in cataract surgery.
PMID- 28410720
TI - Secondary intraocular lens implantation: Complication rates, visual acuity, and
refractive outcomes.
AB - PURPOSE: To compare complication rates, visual acuity, and refractive outcomes of
secondary intraocular lens (IOLs) implantation. SETTING: Department of
Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas,
USA. DESIGN: Retrospective case series. METHODS: All secondary IOLs placed by the
anterior segment service were reviewed. Preoperative data, operative reports, and
data from each subsequent postoperative visit were evaluated. Patients were
divided into 5 groups based on the final IOL position: (1) sulcus with optic
capture, (2) sulcus without optic capture, (3) anterior chamber (AC), (4) iris
fixated, and (5) transscleral-sutured. Complication rates, visual acuity, and
refractive outcomes were compared for each group. RESULTS: The sulcus with and
without optic capture groups had the lowest complication rates and best visual
acuity outcomes. There was no difference in final corrected distance visual
acuity (CDVA) between the transscleral-sutured IOL, iris-fixated IOL, and AC IOL
groups, although the AC IOL group had the lowest rates of early postoperative
complications and a significant improvement in vision. The transscleral-sutured
IOL group had the highest complication rates, and 25% of patients in the iris
fixated IOL group lost 2 or more lines of CDVA. CONCLUSIONS: When a secondary IOL
cannot be placed within the capsular bag, sulcus with optic capture is the best
alternative, followed by sulcus without optic capture. There was no difference in
visual acuity outcomes between transscleral-sutured IOLs, iris-fixated IOLs, and
AC IOLs. Anterior chamber IOLs resulted in fewer early complications.
PMID- 28410721
TI - Microbypass stent implantation with cataract extraction and
endocyclophotocoagulation versus microbypass stent with cataract extraction for
glaucoma.
AB - PURPOSE: To compare the outcomes of combined microbypass stent implantation,
cataract extraction, and endocyclophotocoagulation (ECP) with those of
implantation of the same microbypass stent with concomitant cataract surgery in
patients with open-angle glaucoma (OAG). SETTING: Private Practice, Sioux Falls,
South Dakota, USA. DESIGN: Retrospective consecutive case series. METHODS:
Patients from January 2015 to August 2016 were included. The study group
comprised eyes that had implantation of a microbypass stent in combination with
cataract extraction and ECP. To compare outcomes, a control group of eyes with
similar baseline characteristics that had implantation of a stent in combination
with cataract surgery was established. Data were collected preoperatively and
postoperatively at 1 day, 1 week, and 1, 3, 6, and 12 months. Data included
intraocular pressure (IOP) and number of glaucoma medications. RESULTS: The mean
preoperative IOP was 21.49 mm Hg +/- 9.56 (SD) in the study group (51 eyes) and
20.66 +/- 3.23 mm Hg in the control group (50 eyes). Twelve months
postoperatively, the mean IOP reduction was 7.14 mm Hg in the study group and
4.48 mm Hg in the control group and the medication reduction was 38% (0.68) and
63% (1.06), respectively. CONCLUSIONS: Patients who had implantation of the
microbypass stent in combination with cataract surgery and ECP had significantly
better IOP reduction than those who did not have ECP. The combination procedure
was also effective in patients with severe OAG.
PMID- 28410722
TI - Visual outcomes of laser vision correction in eyes with preoperative amblyopia.
AB - PURPOSE: To evaluate the visual outcomes of photorefractive keratectomy (PRK) and
laser in situ keratomileusis (LASIK) in amblyopic eyes. SETTING: Care Vision
Refractive Clinic, Tel Aviv, Israel. DESIGN: Retrospective case series. METHODS:
Amblyopic eyes of patients with a preoperative corrected distance visual acuity
(CDVA) of 20/33 or worse had PRK or LASIK. Postoperative visual outcomes
(uncorrected distance visual acuity, CDVA) and correlations with age,
preoperative CDVA, refractive error type, astigmatism grade, procedure type,
laser suite model, amblyopia grade, and amblyopia type were analyzed. RESULTS:
This study evaluated 327 eyes (327 patients). The CDVA improved more than 1, 2,
and 3 Snellen lines in 147 eyes (45.0%), 75 eyes (22.9%), and 32 eyes (9.8%),
respectively. Age (P = .007, B = 0.002), and preoperative CDVA (P < .001, B =
0.405) were significantly associated with CDVA improvement. The outcome in eyes
with lower myopia was significantly better than in eyes with hyperopia (0.054
logMAR difference; P = .016) or high myopia (0.036 logMAR difference; P = .002).
Moderately amblyopic eyes had significantly better visual outcomes than mildly
amblyopic eyes (0.038 logMAR difference; P = .001). No significant difference was
found between PRK and LASIK (P = .262). CONCLUSIONS: Laser vision correction,
regardless of the type of procedure (LASIK or PRK) might improve CDVA in a large
portion of amblyopic patients. Improvement was greater in younger patients, eyes
with lower initial CDVA, and eyes with lower myopia.
PMID- 28410723
TI - Risk factors predicting steroid-induced ocular hypertension after photorefractive
keratectomy.
AB - PURPOSE: To assess the risk factors contributing to steroid-induced ocular
hypertension after photorefractive keratectomy (PRK). SETTING: Care Laser
Centers, Tel Aviv, Israel. DESIGN: Retrospective case series. METHODS: Patients
having PRK between January 2000 and December 2015 were followed for at least 3
months. Intraocular pressure (IOP) was measured using the Goldmann applanation
tonometer after 1 week and after 1, 3, and 6 months. Ocular hypertension was
defined as an IOP elevation of 25% while on topical steroid treatment (minimum 28
mm Hg) followed by an IOP drop of 25% when steroid treatment was discontinued.
RESULTS: The study comprised 1783 patients (3566 eyes). The mean age of the
patients was 26.95 years +/- 7.56 (SD), and 54.85% were men. A total of 106 eyes
(2.97%) were steroid responders. The responder group had a higher proportion of
men than the nonresponder group (70.75% versus 29.25%; P < .001), higher central
corneal thickness (CCT) (531.9 +/- 40.2 MUm versus 521.2 +/- 40.9 MUm; P = .008),
lower mean keratometry (K) power (43.39 +/- 1.84 diopters [D] versus 44.08 +/-
1.88 D; P < .001), higher proportion of high myopia (>6.0 D) (31.13% versus
22.18%; P = .03), and higher rate of postoperative corneal haze (16.98% versus
4.25%; P < .001) and were treated postoperatively with more potent steroids. All
factors remained significant in the multivariate analysis. CONCLUSION:
Significant factors associated with post-PRK ocular hypertension were male sex,
high CCT, a low mean K reading, high myopia, corneal haze, and treatment with
stronger steroids such as dexamethasone.
PMID- 28410724
TI - Effects of senofilcon A mechanical protector on corneal endothelial cells during
phacoemulsification in rabbit eyes: Pilot study.
AB - PURPOSE: To evaluate the effects of a senofilcon A mechanical protector against
corneal endothelial cell damage induced by phacoemulsification in rabbit eyes.
SETTING: Department of Ophthalmology, Seoul Metropolitan Government-Seoul
National University Boramae Medical Center, Seoul, South Korea. DESIGN:
Experimental study. METHODS: The endothelial cell count, intraocular pressure
(IOP), and central corneal thickness (CCT) were measured before and 3 days after
the experiment in 26 rabbit eyes randomized into a test group and control group
(6 per group). In study 1, a senofilcon A mechanical protector was inserted into
the anterior chamber in the hard-shell group (test group) whereas, an ophthalmic
viscosurgical device (OVD) was injected in the cohesive group (control group).
Phacoemulsification was performed for a total of 5 minutes (10-second intervals).
In study 2, the soft-shell technique was used in the control group with 5 minutes
of continuous phacoemulsification. In 2 eyes, the safety and toxicity of the
mechanical protector were evaluated. RESULTS: In study 1, there was a 4% loss of
endothelial cells associated with the mechanical protector and an 18% loss after
phacoemulsification in eyes injected with an OVD; the difference between them was
not statistically significant (P = .394). The IOP and CCT also showed
nonsignificant differences in both studies. In study 2, the hard-shell technique
induced significantly less endothelial cell damage than the soft-shell group (P =
.026). Endothelial cell loss caused by the mechanical protector was negligible.
CONCLUSION: The senofilcon A mechanical protector had a protective effect against
corneal endothelial cell damage during phacoemulsification in rabbits.
PMID- 28410725
TI - Optimizing the antisepsis protocol: Effectiveness of 3 povidone-iodine 1.0%
applications versus a single application of povidone-iodine 5.0.
AB - PURPOSE: To determine the minimum effective concentration of povidone-iodine that
reduces the bacterial load by 3-log10, the U.S. Food and Drug Administration
requirement for antiseptic agents, and to study alternative dosing schedules of
povidone-iodine to optimize its bactericidal effect. SETTING: Microbiology
Laboratory, Evanston Hospital, Evanston, Illinois, USA. DESIGN: Experimental
study. METHODS: A standard 0.5 McFarland solution of Staphylococcus epidermidis
was applied to blood agar plates. The plates were treated with a single
application of povidone-iodine solutions from 10.0% to 0.1% to define the range
of interest. Another set of plates received 3 applications of various povidone
iodine solutions. Microbial growth was evaluated after 24 hours. Standard
deviations with 99.0% and 99.9% confidence intervals for each concentration were
estimated and used to estimate the minimum concentration that reduced the colony
counts by at least 3-log10. RESULTS: Povidone-iodine at 2.5% and higher
concentrations was effective in eliminating S epidermidis with a single
application. Three 30-second applications of povidone-iodine at concentrations of
0.7% and higher resulted in at least a 3-log10 reduction of colonies.
CONCLUSIONS: Povidone-iodine 5.0% has been the standard of care for preoperative
ocular antisepsis for 3 decades. Povidone-iodine 0.7% was as effective as a
bactericidal agent when applied multiple times. This suggests povidone-iodine
1.0%, applied in three 30-second applications for preoperative surface
disinfection might be as effective for preoperative antisepsis.
PMID- 28410726
TI - Surgical techniques and adjuvants for the management of primary and recurrent
pterygia.
AB - The removal and rate of recurrence of pterygium have been discussed for years.
The disorder is highly associated with environmental factors, and recurrence
rates can be unacceptably high and cannot be successfully predicted. New
techniques and graft preparations and postoperative management strategies are
helping to reduce the recurrence rates and provide an ocular surface that is near
ideal for future cataract or refractive surgery. This review discusses the
advantages and disadvantages of various treatment strategies.
PMID- 28410727
TI - Transection and explantation of intraocular lenses using femtosecond lasers.
AB - We present 2 cases in which a femtosecond laser was used in vitro to transect
hydrophilic acrylic intraocular lenses (IOLs). At 8 MUJ with 3 MUm spot
separation and 6 MUm line separation, no charring occurred and there was no
increase in total organic carbon. In vivo, the IOLs were successfully transected
in the capsular bag (Case 1, opaque IOL) and the sulcus (Case 2, subluxated IOL
post-pneumatic displacement of submacular hemorrhage) and explanted through a
clear corneal incision (~3.0 mm). At 3 months, in Case 1, the corrected distance
visual acuity (CDVA) improved from 6/24 to 6/5, astigmatism improved by 0.23
diopters, and endothelial cell density (ECD) remained unchanged (1935 to 2210
cells/mm2); in Case 2, the CDVA was hand motion, astigmatism remained unchanged,
and ECD decreased (1960 to 1600 cells/mm2), possibly as a result of complex
surgery. Femtosecond IOL transection and explantation may be a clinically safe
and feasible option for surgeons.
PMID- 28410728
TI - Corneal collagen crosslinking and pigment dispersion syndrome.
AB - We describe the case of a keratoconus patient with pigment dispersion syndrome
(PDS) who was treated for progressive corneal ectasia with corneal collagen
crosslinking (CXL). Pigment dispersion syndrome has been shown to have associated
morphologic changes of the corneal endothelium. Corneal CXL has the potential to
cause toxicity to the corneal endothelium, and adjacent pigment might increase
the likelihood of damage. In this case, the presence of PDS had no detrimental
effect on the outcome of treatment, and no complications were observed at 12
months follow-up, indicating that it may be safe to perform corneal CXL in the
setting of PDS. This is an important observation as the number of indications for
corneal CXL grows.
PMID- 28410730
TI - March consultation #2.
PMID- 28410729
TI - Retrospective analysis of the effects of using sterile water in addition to
hypoosmolar riboflavin during corneal collagen crosslinking for keratoconus.
PMID- 28410731
TI - March consultation #3.
PMID- 28410732
TI - Delayed epithelial healing after photorefractive keratectomy: March consultation
#1.
PMID- 28410734
TI - March consultation #5.
PMID- 28410733
TI - March consultation #4.
PMID- 28410735
TI - March consultation #6.
PMID- 28410736
TI - Unexpectedly low power formula lens constants.
PMID- 28410737
TI - Reply.
PMID- 28410738
TI - Soft tissue artefacts of skin markers on the lower limb during cycling: Effects
of joint angles and pedal resistance.
AB - Soft tissue artefacts (STA) are a major error source in skin marker-based
measurement of human movement, and are difficult to eliminate non-invasively. The
current study quantified in vivo the STA of skin markers on the thigh and shank
during cycling, and studied the effects of knee angles and pedal resistance by
using integrated 3D fluoroscopy and stereophotogrammetry. Fifteen young healthy
adults performed stationary cycling with and without pedal resistance, while the
marker data were measured using a motion capture system, and the motions of the
femur and tibia/fibula were recorded using a bi-plane fluoroscopy-to-CT
registration method. The STAs with respect to crank and knee angles over the
pedaling cycle, as well as the within-cycle variations, were obtained and
compared between resistance conditions. The thigh markers showed greater STA than
the shank ones, the latter varying linearly with adjacent joint angles, the
former non-linearly with greater within-cycle variability. Both STA magnitudes
and within-cycle variability were significantly affected by pedal resistance
(p<0.05). The STAs appeared to be composed of one component providing the stable
and consistent STA patterns and another causing their variations. Mid-segment
markers experienced smaller STA ranges than those closer to a joint, but tended
to have greater variations primarily associated with pedal resistance and muscle
contractions. The current data will be helpful for a better choice of marker
positions for data collection, and for developing methods to compensate for both
stable and variation components of the STA.
PMID- 28410739
TI - Changes in tendon spatial frequency parameters with loading.
AB - To examine and compare the loading related changes in micro-morphology of the
patellar tendon. Fifteen healthy young males (age 19+/-3yrs, body mass 83+/-5kg)
were utilised in a within subjects matched pairs design. B mode ultrasound images
were taken in the sagittal plane of the patellar tendon at rest with the knee at
90 degrees flexion. Repeat images were taken whilst the subjects were carrying
out maximal voluntary isometric contractions. Spatial frequency parameters
related to the tendon morphology were determined within regions of interest (ROI)
from the B mode images at rest and during isometric contractions. A number of
spatial parameters were observed to be significantly different between resting
and contracted images (Peak spatial frequency radius (PSFR), axis ratio, spatial
Q-factor, PSFR amplitude ratio, and the sum). These spatial frequency parameters
were indicative of acute alterations in the tendon micro-morphology with loading.
Acute loading modifies the micro-morphology of the tendon, as observed via
spatial frequency analysis. Further research is warranted to explore its utility
with regard to different loading induced micro-morphological alterations, as
these could give valuable insight not only to aid strengthening of this tissue
but also optimization of recovery from injury and treatment of conditions such as
tendinopathies.
PMID- 28410740
TI - Serum IgE as biomarker for predicting allergen immunotherapy effectiveness.
PMID- 28410741
TI - Reply.
PMID- 28410742
TI - A delayed neurological syndrome after carbon monoxide intoxication.
PMID- 28410743
TI - Symptomatic cervical myelopathy due to general dystonia: Case report and review
of the literature.
PMID- 28410744
TI - Rapid liver volume increase induced by associating liver partition with portal
vein ligation for staged hepatectomy (ALPPS): Is it edema, steatosis, or true
proliferation?
PMID- 28410745
TI - The vena cava filter mystery and misery.
PMID- 28410746
TI - Erratum to "Comparison of different models predicting the phospholipid-membrane
water partition coefficients of charged compounds" [Chemosphere 144C (2016) 382
391].
PMID- 28410747
TI - Robust guaranteed cost tracking control of quadrotor UAV with uncertainties.
AB - In this paper, a robust guaranteed cost controller (RGCC) is proposed for
quadrotor UAV system with uncertainties to address set-point tracking problem. A
sufficient condition of the existence for RGCC is derived by Lyapunov stability
theorem. The designed RGCC not only guarantees the whole closed-loop system
asymptotically stable but also makes the quadratic performance level built for
the closed-loop system have an upper bound irrespective to all admissible
parameter uncertainties. Then, an optimal robust guaranteed cost controller is
developed to minimize the upper bound of performance level. Simulation results
verify the presented control algorithms possess small overshoot and short setting
time, with which the quadrotor has ability to perform set-point tracking task
well.
PMID- 28410748
TI - A proportional integral estimator-based clock synchronization protocol for
wireless sensor networks.
AB - Clock synchronization is an issue of vital importance in applications of WSNs.
This paper proposes a proportional integral estimator-based protocol (EBP) to
achieve clock synchronization for wireless sensor networks. As each local clock
skew gradually drifts, synchronization accuracy will decline over time. Compared
with existing consensus-based approaches, the proposed synchronization protocol
improves synchronization accuracy under time-varying clock skews. Moreover, by
restricting synchronization error of clock skew into a relative small quantity,
it could reduce periodic re-synchronization frequencies. At last, a pseudo
synchronous implementation for skew compensation is introduced as synchronous
protocol is unrealistic in practice. Numerical simulations are shown to
illustrate the performance of the proposed protocol.
PMID- 28410749
TI - Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated
receptor alpha modulator (SPPARMalpha), in combination with statin treatment: Two
randomised, double-blind, placebo-controlled clinical trials in patients with
dyslipidaemia.
AB - BACKGROUND AND AIMS: Substantial residual cardiovascular risks remain despite
intensive statin treatment. Residual risks with high triglyceride and low high
density lipoprotein cholesterol are not the primary targets of statins. K-877
(pemafibrate) demonstrated robust efficacy on triglycerides and high-density
lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of
these studies was to evaluate the efficacy and safety of K-877 add-on therapy to
treat residual hypertriglyceridaemia during statin treatment. METHODS: The
objectives were investigated in two, multicentre, randomised, double-blind,
placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1,
0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188
patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration)
mg/day in combination with any statin for 24 weeks in 423 patients. RESULTS: In
both studies, we found a robust reduction in fasting triglyceride levels by
approximately 50% in all combination therapy groups, which was significant
compared to the statin-monotherapy (placebo) groups (p < 0.001). High-performance
liquid chromatography analysis for lipoprotein subfractions revealed that
atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy, i.e.
small low-density lipoproteins decreased whereas larger ones increased, and
larger high-density lipoproteins decreased whereas smaller ones increased. The
incidence rates of adverse events and adverse drug reactions in K-877 combination
therapy groups were comparable to those in statin-monotherapy groups without any
noteworthy event in both studies. CONCLUSIONS: These results strongly support the
favourable benefit-to-risk ratio of K-877 add-on therapy in combination with
statin treatment.
PMID- 28410750
TI - Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra(r))
on the fertilisation biology of broadcast spawning marine invertebrates.
AB - Exposure to synthetic chemicals is a key environmental challenge faced by aquatic
organisms. The time and dose effects of the pharmaceuticals diclofenac,
ibuprofen, and sildenafil citrate on sperm motility and successful fertilisation
are studied using the echinoderms, Asterias rubens and Psammechinus miliaris, and
the polychaete worm Arenicola marina, all important components of the marine
benthos. Motility was reduced for all species when exposed to diclofenac
concentrations >=0.1 MUg/L. Exposure to >=1.0 MUg/L of ibuprofen affected only P.
miliaris gametes and fertilisation success of A. marina. A. rubens and P.
miliaris sperm increased in both percentage motility and swimming velocity when
exposed to sildenafil citrate at concentrations >=18 and >= 50 ng/L,
respectively. Pre-incubation of sperm with sildenafil citrate significantly
increased fertilisation success in A. rubens and P. miliaris but not in A.
marina. Pre-incubated A. rubens oocytes fertilised successfully in ibuprofen.
According to EU Directive 93/67/EEC, diclofenac is classified as a very toxic
substance to gametes of A. rubens, P. miliaris, and A. marina (EC50 = 100-1000
MUg/L) while ibuprofen is classified as very toxic to gametes of P. miliaris but
non-toxic to gametes of A. marina (EC50 > 10,000 MUg/L). The present study
indicates that diclofenac exposure may have negative impacts on invertebrate
reproductive success, whereas ibuprofen potentially may compromise P. miliaris
reproduction. This study provides a valuable insight into the mechanisms that
allow marine invertebrates to survive and reproduce in contaminated and changing
habitats.
PMID- 28410751
TI - Mizagliflozin, a novel selective SGLT1 inhibitor, exhibits potential in the
amelioration of chronic constipation.
AB - Chronic constipation is a highly common functional gastrointestinal disorder that
adversely affects patient quality of life. At present, limited therapeutic
options are available for the treatment of chronic constipation, which indicates
the need for new therapeutic agents. Herein, we report the potential of
mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1)
inhibitor, for the amelioration of chronic constipation. Mizagliflozin's
inhibitory activity against SGLTs was evaluated by an in vitro assay of cells
transiently expressing SGLTs. The safety profile of an initial single dose (2
160mg, orally) and multiple doses (2-20mg, orally, once daily immediately prior
to breakfast on Days 1 and 13, and three times daily immediately prior to every
meal on Days 3-12) of mizagliflozin was determined by performing a phase I study
in healthy male subjects. In addition, the effect of mizagliflozin and
lubiprostone on fecal wet weight was compared using a dog model of loperamide
induced constipation and rat model of low-fiber-diet-induced constipation.
Mizagliflozin potently inhibited human SGLT1 in a highly selective manner. The
results of the phase I study showed mizagliflozin increased stool frequency and
loosened stool consistency; these effects increased progressively with an
increase in the dosage and the number of doses of mizagliflozin. In addition, the
oral administration of mizagliflozin increased fecal wet weight in a dog model of
loperamide-induced constipation and a rat model of low-fiber-diet-induced
constipation, similar to lubiprostone. These results suggest the potential use of
a novel selective SGLT1 inhibitor, mizagliflozin, for the amelioration of chronic
constipation.
PMID- 28410752
TI - Acute Liver Failure Secondary to Neuroblastoma Amplified Sequence Deficiency.
PMID- 28410753
TI - Retrospective review of patients with atypical bisphosphonate related proximal
femoral fractures.
AB - INTRODUCTION: Patients may be at an increased risk of atypical proximal femoral
fractures with prolonged bisphosphonate use. PATIENTS AND METHODS: This was a
retrospective review of patients who sustained a subtrochanteric fracture of the
femur in our department between April 2009 and March 2014. The radiographs were
reviewed for features of atypical femoral fractures as described by the American
Society of Bone Mineral Research. RESULTS: 185 patients were coded according to
the National Hip Fracture Database as having sustained a subtrochanteric fracture
of the femur. Of these, 26 patients had radiographic findings consistent with an
atypical subtrochanteric fracture. 5 patients were excluded as their histology
confirmed malignancy. 12 patients were taking bisphosphonates on admission. All
12 patients were females taking alendronic acid on admission, who sustained the
fracture as the result of minimal or no trauma and underwent long gamma nail
fixation. The mean age was 71.6 years (range 62-79 years). The mean length of
time on bisphosphonates prior to admission was 8.33 years (range 3-25 years).
9/12 patients had pre-existing symptoms for between 5days and 2 years prior to
admission. 1 patient sustained a broken gamma nail 14 weeks post-operatively
requiring revision. The mean time to discharge from theatre was 16days (range 5
57days). The mean time to radiological union in the patients in whom there was
evidence was 24 weeks. CONCLUSIONS: In this small group of patients, management
of this fracture pattern can be complex with the potential for delayed or non
union and prodromal symptoms are common.
PMID- 28410754
TI - Finite element analysis of the influence of anterior talofibular ligament injury
on Hook test results.
AB - AIM: To determine whether the anterior talofibular ligament injury will influence
the Hook test result. METHOD: A three-dimensional model of the ankle was
established based on CT scan of a healthy volunteer and ligament attachment
through references; Four groups (A-D) of operating conditions were set up. In
group A, the anterior and posterior ligaments of the inferior tibiofibular joint
were cut off and the anterior talofibular ligament was kept intact; in group B,
all the anterior and posterior tibiofibular ligaments and the anterior
talofibular ligament were cut off; in group C, the medial and lateral ligaments
of the ankle joint and the inferior tibiofibular ligament were kept intact; in
group D, only the talofibular ligament was cut off and other ligaments were kept
intact. The proximal end of the model was restrained in all four groups, an
outward pulling force of 100N perpendicular to the fibula was applied, and
displacement and rotation of the distal end of the fibula in the four groups was
observed. RESULTS: When the inferior tibiofibular joint injury was associated
with an anterior talofibular ligament injury, the Hook test indicated about
3.19mm of displacement of the distal end of the fibula, and obvious external
rotation occurred due to increased activity of the anterior border of the fibula.
In the other groups, a single inferior tibiofibular joint injury or a single
anterior talofibular ligament injury did not increase displacement or rotation of
the distal end of the fibula.
PMID- 28410755
TI - The clinical trials crisis in gynecologic oncology.
PMID- 28410756
TI - Perioperative sexual interest in women with suspected gynecologic malignancies.
AB - OBJECTIVES: For women with gynecologic cancer, the impact of surgery on sexual
interest and desire in the immediate and later postoperative period is not well
characterized. The objective of this study was to report the perioperative trends
of changing sexual interest and desire in a cohort of women undergoing surgery
for suspected gynecologic malignancies. METHODS: This is an ancillary analysis of
a cohort study analyzing health-related outcomes in women who underwent primary
surgical management of a suspected gynecologic malignancy between 10/2013 and
10/2014. Subjects completed the Patient-Reported Outcomes Measurement Information
System Sexual Function and Satisfaction Questionnaire (PROMIS-SFQ) preoperatively
and questions on sexual interest and desire at one, three, and six months
postoperatively. Bivariate tests and multiple linear regression were used to
analyze data. RESULTS: Of 231 women who completed a baseline PROMIS-SFQ, 187
(81%) completed one-month, 170 (74%) three-month, and 174 (75%) six-month follow
up interviews. Following surgery, 71% of enrolled subjects were diagnosed with a
malignancy. Women age <55 had a greater decrease in sexual interest from baseline
to one month than women age >55 (-5.5+/-1.0 vs -2.3+/-0.9, p=0.02). In a
multivariable analysis, age <55 remained associated with a larger decrease in
sexual interest at one month postoperatively (-4.6, 95% CI: -1.8, -7.4), as did
having cancer vs benign disease for women of all ages (-5.6, 95% CI: -9.6, -1.5).
CONCLUSIONS: This study provides new data regarding the timing and magnitude of
changes in sexual interest following gynecologic oncology procedures.
PMID- 28410757
TI - Outpatient desensitization in selected patients with platinum hypersensitivity
reactions.
AB - Platinum-based chemotherapies are a standard treatment for both initial and
recurrent gynecologic cancers. Given this widespread use, it is important to be
aware of the features of platinum hypersensitivity reactions and the subsequent
treatment of these reactions. There is also increasing interest in the
development of desensitization protocols to allow patients with a history of
platinum hypersensitivity to receive further platinum based therapy. In this
review, we describe the management of platinum hypersensitivity reactions and the
desensitization protocols utilized at our institution. We also describe the
clinical categorizations utilized to triage patients to appropriate
desensitization protocols.
PMID- 28410758
TI - A rare cause of abdominal pain: Isolated superior mesenteric artery dissection.
PMID- 28410759
TI - State-level immigration and immigrant-focused policies as drivers of Latino
health disparities in the United States.
AB - There has been a great deal of state-level legislative activity focused on
immigration and immigrants over the past decade in the United States. Some
policies aim to improve access to education, transportation, benefits, and
additional services while others constrain such access. From a social
determinants of health perspective, social and economic policies are
intrinsically health policies, but research on the relationship between state
level immigration-related policies and Latino health remains scarce. This paper
summarizes the existing evidence about the range of state-level immigration
policies that affect Latino health, indicates conceptually plausible but under
explored relationships between policy domains and Latino health, traces the
mechanisms through which immigration policies might shape Latino health, and
points to key areas for future research. We examined peer-reviewed publications
from 1986 to 2016 and assessed 838 based on inclusion criteria; 40 were included
for final review. These 40 articles identified four pathways through which state
level immigration policies may influence Latino health: through stress related to
structural racism; by affecting access to beneficial social institutions,
particularly education; by affecting access to healthcare and related services;
and through constraining access to material conditions such as food, wages,
working conditions, and housing. Our review demonstrates that the field of
immigration policy and health is currently dominated by a "one-policy, one-level,
one-outcome" approach. We argue that pursuing multi-sectoral, multi-level, and
multi-outcome research will strengthen and advance the existing evidence base on
immigration policy and Latino health.
PMID- 28410760
TI - Deconstructing the relative benefits of a universal glove and gown intervention
on MRSA acquisition.
AB - BACKGROUND: The 20-site Benefits of Universal Glove and Gown (BUGG) study found
that wearing gloves and gowns for all patient contacts in the intensive care unit
(ICU) reduced acquisition rates of meticillin-resistant Staphylococcus aureus
(MRSA). The relative importance of gloves and gowns as a barrier, improved hand
hygiene, and reduced healthcare worker (HCW)-patient contact rates is unknown.
AIM: To determine what proportion of the reduction in acquisition rates observed
in the BUGG study was due to improved hand hygiene, reduced contact rates, and
universal glove and gown use using agent-based simulation modelling. METHODS: An
existing agent-based model to simulate MRSA transmission dynamics in an ICU was
modified, and the model was calibrated using site-specific data. Model validation
was completed using data collected in the BUGG study. A full 2k factorial design
was conducted to quantify the relative benefits of improving each of the
aforementioned factors with respect to MRSA acquisition rates. FINDINGS: Across
40 simulated replications for each factorial design point and intervention site,
approximately 44% of the decrease in MRSA acquisition rates was due to universal
glove and gown use, 38.1% of the decrease was due to improvement in hand hygiene
compliance on exiting patient rooms, and 14.5% of the decrease was due to the
reduction in HCW-patient contact rates. CONCLUSION: Using mathematical modelling,
the decrease in MRSA acquisition in the BUGG study was found to be due primarily
to the barrier effects of gowns and gloves, followed by improved hand hygiene and
lower HCW-patient contact rates.
PMID- 28410761
TI - Impact of surgical site infection on healthcare costs and patient outcomes: a
systematic review in six European countries.
AB - BACKGROUND: Surgical site infections (SSIs) are associated with increased
morbidity and mortality. Furthermore, SSIs constitute a financial burden and
negatively impact on patient quality of life (QoL). AIM: To assess, and evaluate
the evidence for, the cost and health-related QoL (HRQoL) burden of SSIs across
various surgical specialties in six European countries. METHODS: Electronic
databases and conference proceedings were systematically searched to identify
studies reporting the cost and HRQoL burden of SSIs. Studies published post 2005
in France, Germany, the Netherlands, Italy, Spain, and the UK were eligible for
data extraction. Studies were categorized by surgical specialty, and the primary
outcomes were the cost of infection, economic evaluations, and HRQoL. FINDINGS:
Twenty-six studies met the eligibility criteria and were included for analysis.
There was a paucity of evidence in the countries of interest; however, SSIs were
consistently associated with elevated costs, relative to uninfected patients.
Several studies reported that SSI patients required prolonged hospitalization,
reoperation, readmission, and that SSIs increased mortality rates. Only one study
reported QoL evidence, the results of which demonstrated that SSIs reduced HRQoL
scores (EQ-5D). Hospitalization reportedly constituted a substantial cost burden,
with additional costs arising from medical staff, investigation, and treatment
costs. CONCLUSION: Disparate reporting of SSIs makes direct cost comparisons
difficult, but this review indicated that SSIs are extremely costly. Thus,
rigorous procedures must be implemented to minimize SSIs. More economic and QoL
studies are required to make accurate cost estimates and to understand the true
burden of SSIs.
PMID- 28410762
TI - Ultrasound Assessment of Abdominal Muscle Thickness in Women With and Without Low
Back Pain During Pregnancy.
AB - OBJECTIVE: The aim of this preliminary study was to determine the differences in
abdominal musculature thickness, within 1 month of delivery, in women who
experienced back pain during pregnancy compared with those who did not. METHODS:
B-mode ultrasound imaging was used to measure abdominal muscle thickness on 76
postpartum participants who participated in a larger study; 47 women experienced
back pain during pregnancy, and 29 did not. Participant data were stratified by
group, and primary comparisons were based on these grouping across the abdominal
muscles, including rectus abdominis (upper and lower fibers), external oblique,
internal oblique, and transversus abdominis. Means and standard deviations were
also used to set parameters for future studies. RESULTS: In the present study,
there was no difference in any abdominal muscle thickness between groups. Women
with low back pain were significantly shorter (165.19 +/- 6.64 cm) than women who
did not have from back pain during pregnancy (169.38 +/- 7.58 cm). All other
demographics, such as age, weight, and date tested postpartum, were not
significantly different between groups. CONCLUSION: The results of this study
showed no variation in abdominal muscle thickness in women who had back pain
during pregnancy and those who did not.
PMID- 28410763
TI - Correlation Between Upper Limb Volume and Arterial and Venous Blood Flow Velocity
in Lymphedema Secondary to Breast Cancer Treatment.
AB - OBJECTIVE: The purpose of this study was to correlate upper limb volume and
arterial and venous blood flow velocity in breast cancer survivors. METHODS: A
cross-sectional study was conducted on 30 women with lymphedema and a mean age of
55.60 years (standard deviation = 8.12). For the assessment of upper limb volume,
perimetry was performed with measures at 6 points on the limb, which were
mathematically calculated as volume. The blood flow velocity of the axillary and
brachial arteries and veins were assessed by Doppler ultrasound with a probe at 4
MHz. In the statistical analysis, a Shapiro-Wilk test determined a non-normal
data distribution. Spearman correlation coefficients (rho) were calculated to
determine the association between the variables blood flow velocity and
lymphedema volume. RESULTS: We identified significant and positive associations
between all variables correlated with limb volume: blood flow velocity of the
axillary artery (rho = 0.381, P = .041), axillary vein (rho = 0.383, P = .039),
brachial artery (rho = 0.375, P = .044), and the brachial vein (rho = 0.373, P =
.045). CONCLUSION: There is a positive association between limb volume and blood
flow velocity in the upper limbs of women with lymphedema secondary to breast
cancer treatment.
PMID- 28410764
TI - beta-Trace Protein Assays: A Comparison Between Nephelometric and ELISA
Methodologies.
PMID- 28410765
TI - Development of Nephrolithiasis in Asymptomatic Hyperuricemia: A Cohort Study.
AB - BACKGROUND: Although the association between gout and nephrolithiasis is well
known, the relationship between asymptomatic hyperuricemia and the development of
nephrolithiasis is largely unknown. STUDY DESIGN: Cohort study. SETTING &
PARTICIPANTS: 239,331 Korean adults who underwent a health checkup examination
during January 2002 to December 2014 and were followed up annually or biennially
through December 2014. PREDICTOR: Baseline serum uric acid levels of
participants. OUTCOME: The development of nephrolithiasis during follow-up.
MEASUREMENTS: Nephrolithiasis is determined based on ultrasonographic findings. A
parametric Cox model was used to estimate the adjusted HRs of nephrolithiasis
according to serum uric acid level. RESULTS: During 1,184,653.8 person-years of
follow-up, 18,777 participants developed nephrolithiasis (incidence rate, 1.6/100
person-years). Elevated uric acid level was significantly associated with
increased risk for nephrolithiasis in a dose-response manner (P for trend <
0.001) in men. This dose-response association was not observed in women. In male
participants, multivariable-adjusted HRs for incident nephrolithiasis comparing
uric acid levels of 6.0 to 6.9, 7.0 to 7.9, 8.0 to 8.9, 9.0 to 9.9, and
>=10.0mg/dL with uric acid levels < 6.0mg/dL were 1.06 (95% CI, 1.02-1.11), 1.11
(95% CI, 1.05-1.16), 1.21 (95% CI, 1.13-1.29), 1.31 (95% CI, 1.17-1.46), and 1.72
(95% CI, 1.44-2.06), respectively. This association was observed in all
clinically relevant subgroups and persisted even after adjustment for homeostasis
model assessment of insulin resistance and high-sensitivity C-reactive protein
level. LIMITATIONS: Dietary information and computed tomographic diagnosis of
nephrolithiasis were unavailable. CONCLUSIONS: In this large cohort study,
increased serum uric acid level was modestly and independently associated with
increased risk for the development of nephrolithiasis in a dose-response manner
in apparently healthy men.
PMID- 28410767
TI - Non-anesthesiologist-administered Propofol is not Related to an Increase in
Transcutaneous CO2 Pressure During Flexible Bronchoscopy Compared to Guideline
based Sedation: A Randomized Controlled Trial.
AB - INTRODUCTION: Evidence for the use of non-anesthesiologist-administered propofol
for sedation during flexible bronchoscopy is scarce. The main objective of this
study was to determine whether non-anesthesiologist-administered propofol
balanced sedation was related to higher transcutaneous CO2 pressure compared with
current guideline-based sedation (combination midazolam and opioid). Secondary
outcomes were post-procedural recuperation time, patient satisfaction and
frequency of adverse events. METHODS: In this randomized controlled trial we
included data from outpatients aged 18 years or older with an indication for
flexible bronchoscopy in a university hospital in northern Mexico. RESULTS:
Ninety-one patients were included: 42 in the midazolam group and 49 in the
propofol group. During 60min of transcutaneous capnometry monitoring, mean
transcutaneous CO2 pressure values did not differ significantly between groups
(43.6 [7.5] vs. 45.6 [9.6]mmHg, P=.281). Propofol was related with a high Aldrete
score at 5, 10, and 15min after flexible bronchoscopy (9 [IQR 6-10] vs. 10
[9,10], P=.006; 9 [8-10] vs. 10 [IQR 10-10], P<.001 and 10 [IQR 9-10] vs. 10
[10], respectively) and with high patient satisfaction on a visual analogue scale
of 1 (not satisfied) to 10 (very satisfied) (8.41 [1.25] vs. 8.97 [0.98], P=.03).
Frequency of adverse events was similar among groups (30.9% vs. 22.4%, P=.47).
CONCLUSION: Compared with guideline-recommended sedation, non-anesthesiologist
administered propofol balanced sedation is not associated with higher
transcutaneous CO2 pressure or with more frequent adverse effects. Propofol use
is associated with faster sedation recovery and with high patient satisfaction.
CLINICAL TRIAL REGISTRATION: NCT02820051.
PMID- 28410766
TI - Endobronquial leiomyoma: Outcome of conservative management.
PMID- 28410768
TI - [Small fiber neuropathy].
AB - Small fiber neuropathy (SFN) is still unknown. Characterised by neuropathic pain,
it typically begins by burning feet, but could take many other expression. SFN
affects the thinly myelinated Adelta and unmyelinated C-fibers, by an inherited
or acquired mechanism, which could lead to paresthesia, thermoalgic disorder or
autonomic dysfunction. Recent studies suggest the preponderant role of ion
channels such as Nav1.7. Furthermore, erythromelalgia or burning mouth syndrome
are now recognized as real SFN. Various aetiologies of SFN are described. It
could be isolated or associated with diabetes, impaired glucose metabolism,
vitamin deficiency, alcohol, auto-immune disease, sarcoidosis etc. Several
mutations have recently been identified, like Nav1.7 channel leading to
channelopathies. Diagnostic management is based primarily on clinical examination
and demonstration of small fiber dysfunction. Laser evoked potentials,
Sudoscan(r), cutaneous biopsy are the main test, but had a difficult access.
Treatment is based on multidisciplinary management, combining symptomatic
treatment, psychological management and treatment of an associated etiology.
PMID- 28410769
TI - [Granulomatous periocular eruption].
AB - BACKGROUND: Herein, we report a case of atypical periorificial dermatitis in a
patient that had been receiving treatment for some time for atopic dermatitis.
The specific feature of this rash was its periocular predominance with no
perioral involvement, its clinical aspect and its histological picture evocative
of sarcoidosis. PATIENTS AND METHODS: A 33-year-old man was being treated for a
atopic dermatitis limited to the face and poorly responsive to dermal
corticosteroids. Treatment was initiated with topical tacrolimus 0.1%. After 4
years, dependence on this treatment was noted, with daily application being
needed to control the lesions. One year later, symmetric lesions were seen on the
eyelids and periorbital regions; these were erythematous, micropapular and poorly
delineated in a setting of oedema. Biopsy revealed epithelioid granulomatous
inflammation, and, to a lesser degree, sarcoidal giant-cell features without
caseous necrosis. Staging tests to identify systemic sarcoidosis were negative.
Treatment with hydroxychloroquine at 400mg per day and discontinuation of topical
tacrolimus resulted in complete remission of the lesions within 2 months.
Hydroxychloroquine was discontinued after 6 months, and no relapses had occurred
after 2 years of follow-up. DISCUSSION: Three diagnostic hypotheses may be
posited for these granulomatous facial lesions. We opted for a diagnosis of
granulomatous periorificial dermatitis despite the fact that exclusively
periorbital involvement is rare (this condition is generally associated with
perioral dermatitis). The second was that of pure cutaneous sarcoidosis, but the
topography and clinical appearance of the lesions did not correspond to any of
the cutaneous forms classically described. The third was that of tacrolimus
induced granulomatous rosacea, but the histological picture is different.
CONCLUSION: The present case underscores the fact that a histological appearance
of sarcoidosis on skin biopsy may be associated with perioral dermatitis.
PMID- 28410770
TI - Calcium signaling and cellular senescence.
AB - Cellular senescence is a stable cell proliferation arrest induced by a variety of
stresses including telomere shortening, oncogene activation and oxidative stress.
This process plays a crucial role in many physiopathological contexts, especially
during aging when cellular senescence favors development of age-related diseases,
shortening lifespan. However, the molecular and cellular mechanisms controlling
senescence are still a matter of active research. In the last decade, there has
been emerging literature indicating a key involvement of calcium signaling in
cellular senescence. In this review we will initially give an account of the
direct evidence linking calcium and the regulation of senescence. We will then
review our current knowledge on the role of calcium in some senescence-associated
features and physiopathological conditions, which will shed light on additional
ways in which calcium signaling is implicated in cellular senescence.
PMID- 28410771
TI - The esophageal cooling device: A new temperature control tool in the
intensivist's arsenal.
AB - BACKGROUND: Therapeutic hypothermia has been demonstrated to improve neurological
outcome in comatose survivors of cardiac arrest. Current temperature control
modalities however, have several limitations. Exploring innovative methods of
temperature management has become a necessity. METHODS: We describe the first use
of a novel esophageal cooling device as a sole modality for hypothermia
induction, maintenance and rewarming in a series of four postcardiac arrest
patients. The device was inserted in a manner similar to standard orogastric
tubes and connected to an external heat exchange unit. RESULTS: A mean cooling
rate of 0.42 degrees C/hr (SD +/- 0.26) was observed. An average of 4 hr 24 min
(SD +/- 2 hr 6 min) was required to reach target temperature, and this was
maintained 90.25% (SD +/- 16.20%) of the hypothermia protocol duration. No
adverse events related to device use were encountered. Questionnaires
administered to ICU nursing staff regarding ease-of-use of the device and its
performance were rated as favorable. CONCLUSIONS: When used as a sole modality,
objective performance parameters of the esophageal-cooling device were found to
be comparable to standard temperature control methods. More research is required
to further quantify efficacy, safety, assess utility in other patient
populations, and examine patient outcomes with device use in comparison to
standard temperature control modalities.
PMID- 28410772
TI - Recovery of quantum efficiency in spin-polarized photocathodes by atomic hydrogen
cleaning.
AB - We demonstrate a new method of cleaning superlattice (SL) photocathodes using
atomic hydrogen that allows an increased number of repeat activations. GaAs/GaAsP
SL photocathodes were activated with either conventional heat cleaning or atomic
hydrogen cleaning. Repeated heat cleaning was found to gradually lower the
quantum efficiency (QE) of the photocathodes, while a relatively constant QE was
maintained over repeated atomic hydrogen cleaning. These results show that atomic
hydrogen cleaning allows a greater number of photocathode cleanings without a
loss of performance. Analyses of SL photocathodes indicated that the degradation
resulting from heat cleaning can likely be attributed to the build-up of residual
Cs compounds as well as damage to the GaAs cap layer. The present study also
determined the 1/e lifetime for a GaAs/GaAsP SL photocathode to be 7 h at an
initial current of 2.2 uA.
PMID- 28410773
TI - Brain Activity During Phonation in Women With Muscle Tension Dysphonia: An fMRI
Study.
AB - OBJECTIVES: The main objectives of this functional magnetic resonance imaging
(fMRI) study are (1) to investigate brain activity during phonation in women with
muscle tension dysphonia (MTD) in comparison with healthy controls; and (2) to
explain the neurophysiological mechanism of laryngeal hyperfunction/tension
during phonation in patients with MTD. METHODS: Ten women with MTD and fifteen
healthy women participated in this study. The fMRI experiment was carried out
using a block design paradigm. Brain activation during phonation and exhalation
was analyzed using BrainVoyager software. RESULTS: The statistical analysis of
fMRI data has demonstrated that MTD patients control phonation by use of the
auditory, motor, frontal, parietal, and subcortical areas similar to phonation
control by healthy people. Comparison of phonation tasks in the two groups
revealed higher brain activities in the precentral gyrus, inferior, middle and
superior frontal gyrus, lingual gyrus, insula, cerebellum, midbrain, and
brainstem as well as lower brain activities in the cingulate gyrus, superior and
middle temporal gyrus, and inferior parietal lobe in the MTD group. No
differences were found between the two groups regarding exhalation control.
CONCLUSIONS: The findings in this study provide insight into phonation and
exhalation control in patients with MTD. The imaging results demonstrated that in
patients with MTD, altered (higher/lower) brain activities may result in
laryngeal tension and vocal hyperfunction.
PMID- 28410774
TI - Maintaining the Gift of Life: Achieving Adherence in Adolescent Heart Transplant
Recipients.
AB - Since the beginning of United Network of Organ Sharing data collection in 1987, a
total of 8,333 pediatric patients have received a heart transplant in the United
States. Because these patients now have longer graft success with improved care
and immunosuppression, many of them are entering adolescence and young adulthood.
Primary care pediatric nurse practitioners need to be alert to the prevalence of
noncompliance with treatment in heart transplant patients, which continues to be
highest in adolescence. Low compliance in adolescence increases morbidity,
contributes to decreasing quality of life, and is the leading reason for graft
failure and mortality in this age group. This article will review common barriers
to treatment adherence in the adolescent heart transplant patient, discuss the
role of the primary care pediatric nurse practitioner in preventing
noncompliance, and review strategies that the primary care pediatric nurse
practitioner can implement to improve compliance in this patient population.
PMID- 28410775
TI - Don't throw smokeless tobacco users under the bus.
PMID- 28410776
TI - Do not damn tobacco users to ignorance about big differences in deadly products
because you disapprove of the 'bus' they are on.
PMID- 28410777
TI - Evidence for Neurocognitive Improvement After Bariatric Surgery: A Systematic
Review.
AB - BACKGROUND: Bariatric surgery is an effective means of weight reduction in
severely obese patients and correlates with improvements in quality of life,
mental health outcomes, and neurocognition, especially in those with high
psychosocial burden. OBJECTIVE: The primary purpose of this systematic review was
to evaluate the impact of bariatric surgery on long-term neurocognitive
functioning and neuropsychological outcomes. METHODS: OVID Medline and PsychInfo
databases from January 1990 to August 2015 were searched with key terms and
phrases: "bariatric surgery" and "cognition." The inclusion criteria for the
studies included the following: n >= 10, minimum postoperative follow-up of 12
months, and use of formal neurocognitive assessment tools presurgery and
postsurgery. RESULTS: Of 422 identified abstracts, a total of 10 studies met
inclusion criteria and sample sizes ranged from 10-156. Postsurgical follow-up
time ranged from 12-36 months. All 10 studies documented significant improvements
of statistical significance (p < 0.05) in at least 1 neurocognitive domain
following bariatric surgery; 9 studies showed improvements in memory, 4 studies
showed improvement in executive function, and 2 studies showed improvements in
language, and 1 study showed no improvement in any neurocognitive domain.
CONCLUSION: Mental health care providers should consider the effect of
neurocognitive performance on presurgery psychiatric assessments for bariatric
surgery and implications for psychosocial functioning postsurgery. The
aforementioned effect that bariatric surgical intervention has on neurocognition
underscores the complex interrelationship between metabolism and brain function.
Future research should validate the use of neurocognitive screening tools
presurgery and evaluate the impact of neurocognitive changes on neurocognitive,
bariatric, and functional outcomes.
PMID- 28410778
TI - Encephalopathy With Psychosis Following Group A Streptococcal Sepsis-An Immune
Mediated Phenomenon?
PMID- 28410779
TI - Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation
Treatment for Liver Metastases for Use in Future Economic Evaluations.
AB - AIM: Stereotactic body radiation therapy (SBRT) is increasingly used as an option
for those with liver metastases. In order to facilitate future economic impact of
health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D)
preference-based healthy utility instrument was used to evaluate the impact of
treatment with SBRT on health utility scores. MATERIALS AND METHODS: Between
August 2013 and October 2014, 31 patients treated with 3-5 fractions of SBRT for
liver metastases were enrolled in this study. The EQ-5D instrument was
administered at baseline, during and up to 6 months post-SBRT. RESULTS: Mean EQ
5D score at baseline was 0.857, which remained stable across the entire study
time period. Transient increases in difficulties with mobility (9.7% reported at
baseline to 16.1% on the last day of treatment) and usual activities (3.2%
reported at baseline to 34.5% on day two) were found during the course of
treatment; these returned to baseline levels subsequently. The mean visual
analogue score at baseline was 65.8 and remained unchanged throughout treatment
and follow-up. CONCLUSIONS: The stability of health utility scores and problems
reported by patients undergoing treatment indicate that SBRT for liver metastases
does not impart a significant adverse effect on quality of life. These results
may be used for future economic evaluation of SBRT.
PMID- 28410780
TI - Analyzing interactions on combining multiple clinical guidelines.
AB - Accounting for patients with multiple health conditions is a complex task that
requires analysing potential interactions among recommendations meant to address
each condition. Although some approaches have been proposed to address this
issue, important features still require more investigation, such as (re)usability
and scalability. To this end, this paper presents an approach that relies on
reusable rules for detecting interactions among recommendations coming from
various guidelines. It extends a previously proposed knowledge representation
model (TMR) to enhance the detection of interactions and it provides a systematic
analysis of relevant interactions in the context of multimorbidity. The approach
is evaluated in a case study on rehabilitation of breast cancer patients,
developed in collaboration with experts. The results are considered promising to
support the experts in this task.
PMID- 28410781
TI - Virtual screen to NMR (VS2NMR): Discovery of fragment hits for the CBP
bromodomain.
AB - Overexpression of the CREB-binding protein (CBP), a bromodomain-containing
transcription coactivator involved in a variety of cellular processes, has been
observed in several types of cancer with a correlation to aggressiveness. We have
screened a library of nearly 1500 fragments by high-throughput docking into the
CBP bromodomain followed by binding energy evaluation using a force field with
electrostatic solvation. Twenty of the 39 fragments selected by virtual screening
are positive in one or more ligand-observed nuclear magnetic resonance (NMR)
experiments. Four crystal structures of the CBP bromodomain in complex with in
silico screening hits validate the pose predicted by docking. Thus, the success
ratio of the high-throughput docking procedure is 50% or 10% if one considers the
validation by ligand-observed NMR spectroscopy or X-ray crystallography,
respectively. Compounds 1 and 3 show favorable ligand efficiency in two different
in vitro binding assays. The structure of the CBP bromodomain in the complex with
the brominated pyrrole 1 suggests fragment growing by Suzuki coupling.
PMID- 28410782
TI - Posterior Arthroscopic Tibiotalar Arthrodesis: Anatomic Feasibility Study.
AB - Anterior arthroscopic tibiotalar arthrodesis has been well codified. A posterior
approach with the patient in prone position is indicated when the anterior
approach is precluded by soft tissue issues or for a 1-step procedure associated
with posterior subtalar fusion. In an anatomic study, we assessed the feasibility
of posterior arthroscopic tibiotalar fusion and sought to determine the
arthroscopy entry points, mortise cartilage freshening quality, and risk of
osseous, tendinous, vascular, and neural complications. We mapped 22 zones of the
fibular tibiotalar mortise from 10 specimens. Medial and lateral para-Achilles
arthroscopic approaches were used, with a 4-mm arthroscope at 30 degrees . For
chondral resection, we used a motorized burr, curette, and osteotome. The entire
plafond of the tibial mortise could be freshened in all cases, but the talar dome
could be freshened in its entirety in only 20% of cases. In 80%, only the
posterior two thirds could be treated, because the anterior portion descending to
the neck of the talus was poorly accessible. More than 50% of the area of the
malleolar grooves was freshened. One medial malleolar fracture and one posterior
fibular artery lesion developed. Thus, the technique was shown to be feasible, if
no frontal hindfoot deformity or tibiotalar equinus is present, which would
prevent satisfactory resection of the posterior and anterior talar cartilage. The
procedure allows for single-step associated subtalar fusion, requiring 2
complementary arthroscopic approaches, 1 cm distally.
PMID- 28410783
TI - Editorial Comment.
PMID- 28410784
TI - Author Reply.
PMID- 28410785
TI - Plastic litter in sediments from the coasts of south Tuscany (Tyrrhenian Sea).
AB - This study estimated the total loads of plastic litter (macro-meso- and micro
plastics) in sediments from a wide stretch of marine and coastal environment of
Tyrrhenian Sea. The prevailing category of debris was microplastic. The results
obtained, in terms of average amount of microplastic per kilogram of dry
sediment, are in agreement with data reported by various Authors internationally.
The study area resulted to be uniform for plastic items levels. Particularly
evident was the influence of a flood, occurred in November 2012 in Talamone, on
sediments collected at the harbour of this locality: in this area, a difference
in levels and quality of plastic debris, attributable to periods before and after
the flood, was observed in sediments. In addition to focusing on the effect of
this phenomenon, this study gives an important overview, for what concerns the
presence of plastic litter, of a significant naturalistic area.
PMID- 28410786
TI - The use of ECMO for gastroschisis and omphalocele: Two decades of experience.
AB - PURPOSE: The aim was to review the respiratory failure causes and outcomes of
infants with omphalocele or gastroschisis receiving ECMO and reported to the
Extracorporeal Life Support Organization (ELSO). METHODS: Gastroschisis and
omphalocele infants supported with ECMO and reported to the ELSO Registry between
1992 and 2015 were retrospectively reviewed. Clinical variables, diagnosis of
respiratory failure (pulmonary hypertension (PHN), congenital heart defects
(CHD), congenital diaphragmatic hernia (CDH), and sepsis), and outcomes were
recorded. Univariate analysis was performed using Student's t-test for continuous
or Fisher's exact test for categorical variables. RESULTS: Fifty-two infants with
gastroschisis (41) (79%) or omphalocele (11) (21%) were identified. The survival
to discharge rate of 51% for gastroschisis remained stable and was significantly
higher (P=0.05). The overall mortality rate for omphalocele was 82%. Omphalocele
had significantly more PHN (P<0.01), CDH (P<0.01), and multiple anomalies
(P=0.04) had significantly more sepsis (P=0.02), and none had a CDH. CONCLUSION:
Infants with gastroschisis requiring ECMO support have significantly better
survival than omphaloceles, and respiratory failure is significantly associated
with sepsis. The majority of omphalocele infants die despite ECMO, and
respiratory failure is associated PHN and CDH. The association of omphalocele,
PHN, and CDH merits further investigation. STUDY TYPE AND EVIDENCE LEVEL:
Retrospective comparative study of Registry Database, Level 3.
PMID- 28410787
TI - Efficacy of nitroglycerine ointment in the treatment of pediatric anal fissure.
AB - BACKGROUND: Anal fissure is the most common anal disease in children. In the past
few decades, the understanding of its pathophysiology has led to a progressive
reduction in invasive procedures in favor of conservative treatment based on
stool softeners and the relaxation of the anal sphincter. This randomized
controlled study assessed the safety and efficacy of nitroglycerine (NTG)
ointment in the treatment of pediatric anal fissure, which had not yet been
proved. PATIENTS AND METHODS: An unequal randomized controlled study included 105
pediatric patients with anal fissure who had presented to the private and
outpatient clinics of the Central Teaching Hospital of Pediatrics during the
period from February 2015 to May 2016. The control group consisted of 70
patients. Both groups were treated with classical conservative therapy of sitz
bath, stool softener, and local anesthetic. In the second group, chemical
sphincterotomy with 0.2% NTG ointment was used in 35 patients, and was applied at
the anal canal twice daily for 8weeks. The primary outcomes of symptomatic
improvement and healed fissure, as well as side effects, were analyzed. RESULTS:
The average age of patients was 2years (range, 4months to 5years). Patients in
the NTG group had 77% symptomatic relief and 60% healed fissure compared to the
control group, which had 54% and 32.8% respectively. All were statistically
significant. No serious adverse effects were noticed during the treatment period.
CONCLUSION: The use of 0.2% NTG ointment is an effective therapy for anal fissure
in children in terms of good healing rate and rapid symptom relief, but it has
the drawback of a long treatment period, making patient compliance more
difficult, in addition to the problems of tolerance and recurrence. TYPE OF
STUDY: Prospective randomized controlled study (treatment study). LEVEL OF
EVIDENCE: Type 2.
PMID- 28410788
TI - Independence of gut bacterial content and neonatal necrotizing enterocolitis
severity.
AB - INTRODUCTION: Necrotizing enterocolitis (NEC) is a common and devastating
gastrointestinal disease of premature infants. NEC severity varies widely. Recent
data have demonstrated a strong link between gut microbial dysbiosis and
development of NEC. We tested the hypothesis that alterations in the gut
microbiome at the time of diagnosis predict the severity of NEC. METHODS: We used
prospectively collected fecal samples from very low birth weight infants who
developed NEC, stratifying by NEC severity. Fecal bacterial DNA was sequenced
using 16S rRNA pyrosequencing. A generalized Wald-type test based on the
Dirichlet multinomial distribution was used to test for differences in microbial
communities. RESULTS: Of 489 infants at risk, 30 NEC cases had 410 fecal samples
collected in the 28days prior to the onset of NEC available for analysis. There
were no differences in the pre-NEC gut microbial community between infants
treated medically vs. surgically, or those with NEC totalis. Furthermore, neither
treatment of NEC significantly changed the gut microbiome post-NEC among the
survivors. CONCLUSION: We found no evidence that the gut microbiome, prior to the
onset of disease, differentiates the clinical course of NEC. These data suggest
that factors other than the gut microbiome may dictate disease severity. LEVEL OF
EVIDENCE: Level 4.
PMID- 28410790
TI - Which multi-trauma patients benefit from performing a total-body CT?
PMID- 28410789
TI - Duodenogastric regurgitation in hepaticoduodenostomy after excision of congenital
biliary dilatation (choledochal cyst).
AB - PURPOSE: We examined the clinical significance of duodenogastric regurgitation
(DGR) as a late complication in the long-term follow-up after
hepaticoduodenostomy (HD) as a reconstruction surgery for congenital biliary
dilatation (CBD). METHODS: Seventeen patients with CBD were retrospectively
analyzed for late complications (mean follow-up, 16.8 years). All patients had
undergone total resection of the extrahepatic bile duct followed by HD. DGR was
identified using endoscopic examination, intraluminal bile monitoring, and liver
scanning. RESULTS: DGR was found in all 17 patients by endoscopic examination and
intraluminal bile monitoring. Fourteen of the 17 (82.4%) patients with DGR had
experienced abdominal symptoms since a mean of 6.9 years postoperatively. Liver
scanning also revealed apparent DGR in all 14 symptomatic patients. We converted
7 of the 14 patients to hepaticojejunostomy reconstruction at a mean of 13.0
years after the initial excisional surgery. Their symptoms were completely
relieved postoperatively. CONCLUSIONS: DGR is an important complication after HD.
Examination of patients for the development of DGR is an essential part of long
term follow-up in patients with CBD who have undergone HD as a reconstruction
surgery. Conversion surgery is recommended in patients with DGR accompanied by
long-term abdominal symptoms. LEVELS OF EVIDENCE: Level IV.
PMID- 28410791
TI - Gastrointestinal safety of celecoxib versus naproxen in patients with
cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding
(CONCERN): an industry-independent, double-blind, double-dummy, randomised trial.
AB - BACKGROUND: Present guidelines are conflicting for patients at high risk of both
cardiovascular and gastrointestinal events who continue to require non-steroidal
anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2
selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID
plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in
concomitant users of aspirin with previous ulcer bleeding. METHODS: For this
industry-independent, double-blind, double-dummy, randomised trial done in one
academic hospital in Hong Kong, we screened patients with arthritis and
cardiothrombotic diseases who were presenting with upper gastrointestinal
bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing,
an independent staff member randomly assigned (1:1) patients who were negative
for Helicobacter pylori with a computer-generated list of random numbers to
receive oral administrations of either celecoxib 100 mg twice per day plus
esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus
esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg
once per day. Both patients and investigators were masked to their treatments.
The primary endpoint was recurrent upper gastrointestinal bleeding within 18
months. The primary endpoint and secondary safety endpoints were analysed in the
modified intention-to-treat population. This study was registered with
ClinicalTrials.gov, number NCT00153660. FINDINGS: Between May 24, 2005, and Nov
28, 2012, we enrolled 514 patients, assigning 257 patients to each study group,
all of whom were included in the intention-to-treat population. Recurrent upper
gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine
gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group
(25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer,
and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18
months was 5.6% (95% CI 3.3-9.2) in the celecoxib group and 12.3% (8.8-17.1) in
the naproxen group (p=0.008; crude hazard ratio 0.44, 95% CI 0.23-0.82; p=0.010).
Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib
group and 17 (7%) patients in the naproxen group had adverse events leading to
discontinuation of treatment. No treatment-related deaths occurred during the
study. INTERPRETATION: In patients at high risk of both cardiovascular and
gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus
proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent
upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived
cardiovascular safety. FUNDING: The Research Grant Council of Hong Kong.
PMID- 28410793
TI - Paediatric head imaging decisions are not child's play.
PMID- 28410792
TI - Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a
prospective cohort study.
AB - BACKGROUND: Clinical decision rules can help to determine the need for CT imaging
in children with head injuries. We aimed to validate three clinical decision
rules (PECARN, CATCH, and CHALICE) in a large sample of children. METHODS: In
this prospective observational study, we included children and adolescents (aged
<18 years) with head injuries of any severity who presented to the emergency
departments of ten Australian and New Zealand hospitals. We assessed the
diagnostic accuracy of PECARN (stratified into children aged <2 years and >=2
years), CATCH, and CHALICE in predicting each rule-specific outcome measure
(clinically important traumatic brain injury [TBI], need for neurological
intervention, and clinically significant intracranial injury, respectively). For
each calculation we used rule-specific predictor variables in populations that
satisfied inclusion and exclusion criteria for each rule (validation cohort). In
a secondary analysis, we compiled a comparison cohort of patients with mild head
injuries (Glasgow Coma Scale score 13-15) and calculated accuracy using rule
specific predictor variables for the standardised outcome of clinically important
TBI. This study is registered with the Australian New Zealand Clinical Trials
Registry, number ACTRN12614000463673. FINDINGS: Between April 11, 2011, and Nov
30, 2014, we analysed 20 137 children and adolescents attending with head
injuries. CTs were obtained for 2106 (10%) patients, 4544 (23%) were admitted, 83
(<1%) underwent neurosurgery, and 15 (<1%) died. PECARN was applicable for 4011
(75%) of 5374 patients younger than 2 years and 11 152 (76%) of 14 763 patients
aged 2 years and older. CATCH was applicable for 4957 (25%) patients and CHALICE
for 20 029 (99%). The highest point validation sensitivities were shown for
PECARN in children younger than 2 years (100.0%, 95% CI 90.7-100.0; 38 patients
identified of 38 with outcome [38/38]) and PECARN in children 2 years and older
(99.0%, 94.4-100.0; 97/98), followed by CATCH (high-risk predictors only; 95.2%;
76.2-99.9; 20/21; medium-risk and high-risk predictors 88.7%; 82.2-93.4; 125/141)
and CHALICE (92.3%, 89.2-94.7; 370/401). In the comparison cohort of 18 913
patients with mild injuries, sensitivities for clinically important TBI were
similar. Negative predictive values in both analyses were higher than 99% for all
rules. INTERPRETATION: The sensitivities of three clinical decision rules for
head injuries in children were high when used as designed. The findings are an
important starting point for clinicians considering the introduction of one of
the rules. FUNDING: National Health and Medical Research Council, Emergency
Medicine Foundation, Perpetual Philanthropic Services, WA Health Targeted
Research Funds, Townsville Hospital Private Practice Fund, Auckland Medical
Research Foundation, A + Trust.
PMID- 28410794
TI - NSAIDs for high-risk patients: none, celecoxib, or naproxen?
PMID- 28410795
TI - The double burden of malnutrition: a threat for Peruvian childhood.
PMID- 28410796
TI - [Improving diet quality in children through a new nutritional education
programme: INFADIMED].
AB - OBJECTIVE: To assess the results of a nutritional education programme developed
by using available local resources to improve diet quality and decrease
overweight and obesity prevalence among children. METHOD: A longitudinal
intervention study by means of nutritional education (INFADIMED) in children
(aged 3-7 years) from Vilafranca del Penedes (Barcelona, Spain), recruited from
preschool centres and primary schools, with an intervention or INFADIMED group
(n=319; 50.2% female) and a control group (n=880; 49.8% female). Weight, height
and body mass index were measured in both groups at the beginning and at the end
of the programme. Adherence to the Mediterranean diet was also assessed using the
KIDMED test. RESULTS: Consumption of fruit or juices, vegetables, yogurt and/or
cheese, pasta or rice, and nuts increased, while skipping breakfast, consumption
of bakery products for breakfast, and/or consumption of sweets several times per
day decreased in the INFADIMED group. INFADIMED also changed, from the beginning
to the end of the study, the adherence to a Mediterranean diet: high (39.2% to
70.5%), acceptable (49.2% to 28.2%), and low (11.6% to 1.3%). Approximately 2.6%
of the participants in the control group and 11.3% of the participants in the
INFADIMED group who were overweight and obese changed to normal weight (odds
ratio: 4.08; 95% confidence interval: 2.37-7.04). CONCLUSIONS: INFADIMED is a
nutritional education programme with benefits on both diet quality and overweight
and obesity prevalence among children.
PMID- 28410797
TI - [Infobarris: an interactive tool to monitor and disseminate information on health
and its determinants in the neighbourhoods of Barcelona (Spain)].
AB - In order to know about the health of the population, it is necessary to perform a
systematic and continuous analysis of their health status and social and economic
health determinants. The objective of this paper is to describe the development
and implementation of the Infobarris tool, which allows to visualize a wide
battery of indicators and social determinants of health by neighbourhoods in the
city of Barcelona (Spain). For the development of the Infobarris tool, we used an
agile methodology that allows the development of a project in iterative and
incremental stages, which are the following: selection of indicators, design of
the prototype, development of the tool, data loading, and tool review and
improvements. Infobarris displays 64 indicators of health and its determinants
through graphics, maps and tables, in a friendly, interactive and attractive way,
which facilitates health surveillance in the neighbourhoods of Barcelona.
PMID- 28410798
TI - Protective role of CoQ10 or L-carnitine on the integrity of the myocardium in
doxorubicin induced toxicity.
AB - Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different
cancers and its clinical usage is hindered by the oxidative injury-related
cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart
can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study
was performed on seventy two female Wistar albino rats divided into six groups,
12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L
carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L
carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that
injected intraperitoneally (IP) then the treatment continued for 10days. At the
end of the study, serum biochemical parameters of cardiac damage, oxidative
stress indices, and histopathological changes were investigated. CoQ10 or L
carnitine showed a noticeable effects in improving cardiac functions evidenced
reducing serum enzymes as serum interleukin-1 beta (IL-1 beta), tumor necrosis
factor alpha (TNF-alpha), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1,
Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac
Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced
glutathione levels to normal levels. Both corrected the cardiac alterations
histologically and ultrastructurally. With a visible improvements in alpha-SMA,
vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine
supplementation improves the functional and structural integrity of the
myocardium.
PMID- 28410800
TI - Superparamagnetic graphene oxide-based dispersive-solid phase extraction for
preconcentration and determination of tamsulosin hydrochloride in human plasma by
high performance liquid chromatography-ultraviolet detection.
AB - In the present study, superparamagnetic graphene oxide-Fe3O4 nanocomposites were
successfully prepared by a modified impregnation method (MGOmi) and their
application as a sorbent in the magnetic-dispersive solid phase extraction (M
dSPE) mode to the preconcentration and determination of tamsulosin hydrochloride
(TMS) in human plasma was investigated by coupling with high performance liquid
chromatography-ultraviolet detection (HPLC-UV). The structure, morphology and
magnetic properties of the prepared nanocomposites were characterized using X-ray
diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning
electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and
vibrating sample magnetometry (VSM). Some factors affecting the extraction
efficiency, including the pH value, amount of sorbent, extraction time, elution
solvent and its volume, and desorption time were studied and optimized. Magnetic
nanocomposites plasma extraction of TMS following HPLC analyses showed a linear
calibration curve in the range of 0.5-50.0ngmL-1 with an acceptable correlation
coefficient (R2=0.9988). The method was sensitive, with a low limit of detection
(0.17ngmL-1) and quantification (0.48ngmL-1). Inter- and intra-day precision
expressed as relative standard deviation (n=3) and the preconcentration factor,
were found to be 5.6-7.2%, 2.9-4.2% and 10, respectively. Good recoveries (98.1
101.4%) with low relative standard deviations (4.2-5.0%) indicated that the
matrices under consideration do not significantly affect the extraction process.
Due to its high precision and accuracy, the developed method may be a HPLC-UV
alternative with M-dSPE for bioequivalence analysis of TMS in human plasma.
PMID- 28410801
TI - Layer-by-layer self-assembly of polyelectrolyte multilayers on silica spheres as
reversed-phase/hydrophilic interaction mixed-mode stationary phases for high
performance liquid chromatography.
AB - In this study, a series of stationary phases, comprising silica spheres and
polyelectrolyte multilayers (PEMs) as the core and surface coating, respectively,
were prepared via a layer-by-layer self-assembly approach for use in high
performance liquid chromatography. PEMs coatings were formed by the alternate
deposition of positively charged poly(allylamine hydrochloride) and negatively
charged poly(ethylene-alt-maleate) anions which were synthesized by
esterification between poly(ethylene-alt-maleic anhydride) and n-alkyl alcohols
(CnH2n+1OH, n=4, 8, 10, 12). The chromatographic performance and retention
mechanism of the new stationary phases were evaluated in simultaneous reversed
phase/hydrophilic interaction mixed-mode chromatography using different solute
probes, such as alkyl benzene, p-hydroxybenzoic acid and its esters, anilines,
phenols, and pyrimidines. The separation performance of the new stationary phases
was optimized by tuning the n-alkyl chain length of poly(ethylene-alt-maleate)
and bilayer numbers of PEMs. These results indicated that the new stationary
phases demonstrate promise for the simultaneous separation of complex hydrophobic
and hydrophilic samples with high selectivity.
PMID- 28410799
TI - Genomic identification and characterization of the elite strains Bradyrhizobium
yuanmingense BR 3267 and Bradyrhizobium pachyrhizi BR 3262 recommended for cowpea
inoculation in Brazil.
AB - The leguminous inoculation with nodule-inducing bacteria that perform biological
nitrogen fixation is a good example of an "eco-friendly agricultural practice".
Bradyrhizobium strains BR 3267 and BR 3262 are recommended for cowpea (Vigna
unguiculata) inoculation in Brazil and showed remarkable responses; nevertheless
neither strain was characterized at species level, which is our goal in the
present work using a polyphasic approach. The strains presented the typical
phenotype of Bradyrhizobium with a slow growth and a white colony on yeast
extract-mannitol medium. Strain BR 3267 was more versatile in its use of carbon
sources compared to BR 3262. The fatty acid composition of BR 3267 was similar to
the type strain of Bradyrhizobium yuanmingense; while BR 3262 was similar to
Bradyrhizobium elkanii and Bradyrhizobium pachyrhizi. Phylogenetic analyses based
on 16S rRNA and three housekeeping genes placed both strains within the genus
Bradyrhizobium: strain BR 3267 was closest to B. yuanmingense and BR 3262 to B.
pachyrhizi. Genome average nucleotide identity and DNA-DNA reassociation
confirmed the genomic identification of B. yuanmingense BR 3267 and B. pachyrhizi
BR 3262. The nodC and nifH gene analyses showed that strains BR 3267 and BR 3262
hold divergent symbiotic genes. In summary, the results indicate that cowpea can
establish effective symbiosis with divergent bradyrhizobia isolated from
Brazilian soils.
PMID- 28410802
TI - Dispersive micro-solid phase extraction of aromatic amines based on an efficient
sorbent made from poly(1,8-diaminonaphtalen) and magnetic multiwalled carbon
nanotubes composite.
AB - In this work, the extraction of aromatic amines with an efficient magnetic
multiwalled carbon nanotubes/Fe3O4@Poly(1,8-diaminonaphtalen) (MWCNTs/Fe3O4@PDAN)
composite followed by HPLC-DAD was presented. Imprimis, the comparison among
different magnetic nanosorbents including Fe3O4, MWCNTs/Fe3O4, Fe3O4@PDAN and
MWCNTs/Fe3O4@PDAN was conducted. The obtained results, exhibited that the
MWCNTs/Fe3O4@PDAN composite has the highest extraction efficiency for target
analytes (3-nitroaniline, 4-chloroaniline, 4-bromoaniline and 3,4
dichloroaniline). This sorbent was characterized by Fourier transform infrared
spectroscopy, X-ray dispersive spectroscopy, thermogravimetry analysis, scanning
electron microscopy, transition electron microscopy, vibrating sample
magnetometry and X-ray diffraction. Design of experiment approach was applied to
find out the optimal experimental conditions. The optimal extraction conditions
were: pH of the sample, 10; sorbent amount, 10mg; sorption time, 15min; salt
concentration, 10% w/w; type and volume of the eluent, 0.01molL-1 HCl in
acetonitrile, 145MUL; elution time; 2min. Under the optimal extraction conditions
detection limits and linear dynamic ranges were achieved in the range of 0.1
0.25MUgL-1 and 0.25-500MUgL-1, respectively. The percent of extraction recovery
and relative standard deviations (n=5) were in the range of 31.2-82.8% and 3.4
5.6%, respectively. Finally, the applicability of the method was successfully
confirmed by the extraction and determination of target analytes in various water
samples.
PMID- 28410803
TI - Evaluation of the measurement uncertainty: Some common mistakes with a focus on
the uncertainty from linear calibration.
AB - The rational strategy in the evaluation of analytical measurement uncertainty is
to combine the "whole method" performance data, such as precision and recovery,
with the uncertainty contributions from sources not adequately covered by those
data. This paper highlights some common mistakes in evaluating the uncertainty
when pursuing that strategy, as revealed in current chromatographic literature.
The list of the uncertainty components usually taken into account is discussed
first and fallacies with the LOD- and recovery uncertainties are noted. Close
attention is paid to the uncertainty arising from a linear calibration normally
used. It is demonstrated that following a well-known formula for the standard
deviation of an analytical result obtained from a straight line calibration leads
to double counting the precision contribution to the uncertainty budget.
Furthermore, the precision component itself is often estimated improperly, based
on the number of replicates taken from the precision assessment experiment. As a
result, the relative uncertainty from linear calibration is overestimated in the
budget and may become the largest contribution to the combined uncertainty, which
is clearly shown with an example calculation based on the literature data.
PMID- 28410804
TI - Neutron reflectivity measurement of protein A-antibody complex at the solid
liquid interface.
AB - Chromatography is a ubiquitous unit operation in the purification of
biopharmaceuticals yet few studies have addressed the biophysical
characterisation of proteins at the solution-resin interface. Chromatography and
other adsorption and desorption processes have been shown to induce protein
aggregation which is undesirable in biopharmaceutical products. In order to
advance understanding of how adsorption processes might impact protein stability,
neutron reflectivity was used to characterise the structure of adsorbed
immunoglobulin G (IgG) on model surfaces. In the first model system, IgG was
adsorbed directly to silica and demonstrated a side-on orientation with high
surface contact. A maximum dimension of 60A in the surface normal direction and
high density surface coverage were observed under pH 4.1 conditions. In
chromatography buffers, pH was found to influence IgG packing density and
orientation at the solid-liquid interface. In the second model system, which was
designed to mimic an affinity chromatography surface, protein A was attached to a
silica surface to produce a configuration representative of a porous glass
chromatography resin. Interfacial structure was probed during sequential stages
from ligand attachment, through to IgG binding and elution. Adsorbed IgG
structures extended up to 250A away from the surface and showed dependence on
surface blocking strategies. The data was suggestive of two IgG molecules bound
to protein A with a somewhat skewed orientation and close proximity to the silica
surface. The findings provide insight into the orientation of adsorbed antibody
structures under conditions encountered during chromatographic separations.
PMID- 28410805
TI - Startle responses in functional jerky movement disorders are increased but have a
normal pattern.
AB - BACKGROUND: Exaggerated startle reactions have been frequently described in
patients with functional movement disorders (FMD). Long onset latencies and
inconsistent recruitment pattern are thought to be a hallmark in these patients.
The auditory startle reflex has not been systematically assessed though.
OBJECTIVES: Assessing the frequency and pattern of the early and late component
of the auditory startle response in patients with functional jerky movement
disorders. METHODS: A case-control design was used to study 17 patients with
functional jerky movement disorders and 15 healthy gender- and age-matched
control subjects. The auditory startle reflex was elicited by 108 dB loud tones
and assessed with electromyography in multiple muscles. RESULTS: Response
probability of the early and the late response were significantly enlarged in
patients with FMD. The early response showed a normal muscle recruitment pattern
whereas the late response revealed a more variable pattern compared to controls.
The early and late responses showed normal habituation in both groups.
Remarkably, a high response rate of the abdominal muscle was noted especially in
patients suffering from abdominal jerks. CONCLUSIONS: This study shows enlarged,
but normally patterned early startle responses in FMD. The high response
frequency of the late responses found in these patients reflects a behavioral
component. Hypersensitivity to external stimuli, often noted in FMD is supported
by high response probabilities of both components of the auditory startle
response.
PMID- 28410806
TI - External costs of PM2.5 pollution in Beijing, China: Uncertainty analysis of
multiple health impacts and costs.
AB - Some cities in China are facing serious air pollution problems including high
concentrations of particles, SO2 and NOx. Exposure to PM2.5, one of the primary
air pollutants in many cities in China, is highly correlated with various adverse
health impacts and ultimately represents a cost for society. The aim of this
study is to assess health impacts and external costs related to PM2.5 pollution
in Beijing, China with different baseline concentrations and valuation methods.
The idea is to provide a reasonable estimate of the total health impacts and
external cost due to PM2.5 pollution, as well as a quantification of the relevant
uncertainty. PM2.5 concentrations were retrieved for the entire 2012 period in 16
districts of Beijing. The various PM2.5 related health impacts were identified
and classified to avoid double counting. Exposure-response coefficients were then
obtained from literature. Both the value of statistical life (VSL) and the
amended human capital (AHC) approach were applied for external costs estimation,
which could provide the upper and lower bound of the external costs due to PM2.5.
To fully understand the uncertainty levels, the external cost distribution was
determined via Monte Carlo simulation based on the uncertainty of the parameters
such as PM2.5 concentration, exposure-response coefficients, and economic cost
per case. The results showed that the external costs were equivalent to around
0.3% (AHC, China's guideline: C0 = 35 MUg/m3) to 0.9% (VSL, WHO guideline: C0 =
10 MUg/m3) of regional GDP depending on the valuation method and on the assumed
baseline PM2.5 concentration (C0). Among all the health impacts, the economic
loss due to premature deaths accounted for more than 80% of the overall external
costs. The results of this study could help policymakers prioritizing the PM2.5
pollution control interventions and internalize the external costs through the
application of economic policy instruments.
PMID- 28410807
TI - Assessing impacts of the WHO FCTC on national legislations: A case study of the
Republic of Korea.
AB - The World Health Organization Framework Convention on Tobacco Control (WHO FCTC)
is an international treaty that was adopted in 2003 with the aim of addressing
public health problems related to tobacco. The treaty is expected to bring
substantial changes to global tobacco control because it has legally binding
power over its signatory countries. However, its actual impact on national
legislative processes, to date, has not been thoroughly examined. This article
assesses the effect of the WHO FCTC on national tobacco legislation, with the
Republic of Korea as a case study. This article also reviews whether and how
lawmakers and government officials actually refer to the WHO FCTC as a
justification for amending tobacco law after Korea ratified the WHO FCTC in 2005.
This review shows that the WHO FCTC served as an important ground upon which to
amend laws to strengthen tobacco control in Korea. The legally binding power of
the WHO FCTC compelled lawmakers to comply with international standards.
Furthermore, various tobacco control measures listed in the treaty have provided
practical tips for Korean policymakers to refer to in designing tobacco control
laws.
PMID- 28410808
TI - Questioning the differences between general public vs. patient based preferences
towards EQ-5D-5L defined hypothetical health states.
AB - The purpose of this article is to explore whether any differences exist between
the general population and patient based preferences towards EQ-5D-5L defined
hypothetical health states. The article discusses the role of adaptation and self
interest in valuing health states and it also contributes rigorous empirical
evidence to the scientific debate on the differences between the patient and
general population preferences towards hypothetical health states. Patient
preferences were elicited in 2015 with the EQ-5D-5L questionnaire using time
trade-off and discrete choice experiment design and compared to the Spanish
general population preferences, which were elicited using identical methods.
Patients were chosen on a voluntary basis according to their willingness to
participate in the survey. They were recruited from patient organisations and a
hospital in Madrid, Spain. 282 metastatic breast cancer patients and 333
rheumatoid arthritis patients were included in the sample. The analysis revealed
differences in preferences between the general population and patient groups.
Based on the results of our analysis, it is suggested that the differences in
preferences stem from patients being more able to accurately imagine "non
tangible" dimensions of health states (anxiety or depression, and pain or
discomfort) than the general population with less experience in various health
states. However, this does not mean that general public values should not be
reflected in utilities derived for coverage decision making.
PMID- 28410809
TI - A randomized phase II trial of concurrent chemoradiation with two doses of
radiotherapy, 60Gy and 66Gy, concomitant with a fixed dose of oral vinorelbine in
locally advanced NSCLC.
AB - INTRODUCTION: In order to test the best performing radiation dose with a
convenient chemotherapy schedule of an oral formulation of radio-sensitizing
vinorelbine in inoperable locally advanced non-small cell lung cancer (NSCLC), we
performed a randomized phase II trial based on a "pick the winner" design.
METHODS: After 2 cycles of neoadjuvant chemotherapy, 117 patients with NSCLC
stage IIB-IIIB in performance status 0-1 were randomized to radiotherapy 60Gy/30
fractions or 66Gy/33 fractions concurrent with a fixed dose of oral vinorelbine
50mg administered 3 times weekly. The primary endpoint was local progression free
interval. A scheduled FDG-PET-CT-scan was performed 9months after randomization.
The study was registered at ClinicalTrials.gov (NCT 00887783). RESULTS: Both arms
were well tolerated. The local progression free interval at 9months was 54% in
the 60Gy arm and 59% in the 66Gy arm (log rank test p=0.55). There was no
statistically significant difference in overall survival. The median survival was
23.3 and 23.7months in the 60 and 66Gy arm, respectively. No significant
difference in toxicity was observed. CONCLUSION: Both 60 and 66Gy administered
concomitant with oral vinorelbine showed similar local control and overall
survival, and was well tolerated. The pick the winner design choose 66Gy as the
winning arm.
PMID- 28410810
TI - To screen or not to screen for obstructive sleep apnea, that is the question.
PMID- 28410811
TI - Long-term non-invasive ventilation therapies in children: A scoping review.
AB - Long-term non-invasive ventilation (NIV) is a common modality of breathing
support used for a range of sleep and respiratory disorders. The aim of this
scoping review was to provide a summary of the literature relevant to long-term
NIV use in children. We used systematic methodology to identify 11,581 studies
with final inclusion of 289. We identified 76 terms referring to NIV; the most
common term was NIV (22%). Study design characteristics were most often single
center (84%), observational (63%), and retrospective (54%). NIV use was reported
for 73 medical conditions with obstructive sleep apnea and spinal muscular
atrophy as the most common conditions. Descriptive data, including NIV incidence
(61%) and patient characteristics (51%), were most commonly reported. Outcomes
from sleep studies were reported in 27% of studies followed by outcomes on
reduction in respiratory morbidity in 19%. Adverse events and adherence were
reported in 20% and 26% of articles respectively. Authors reported positive
conclusions for 73% of articles. Long-term use of NIV has been documented in a
large variety of pediatric patient groups with studies of lower methodological
quality. While there are considerable data for the most common conditions, there
are fewer data to support NIV use for many additional conditions.
PMID- 28410812
TI - CD4+ T cells support establishment of RSV-specific IgG and IgA antibody secreting
cells in the upper and lower murine respiratory tract following RSV infection.
AB - The RSV vaccine field suffered a major set-back when children were vaccinated
with a formalin-inactivated RSV vaccine (FI-RSV). Unexpectedly, the vaccinated
children fared worse than unvaccinated children when they were naturally infected
with RSV. Mouse models were then developed that implicated the CD4+ T helper cell
population as a contributor to adverse events. Today, the T cell is viewed with
much caution in the RSV field, and its induction by vaccination is sometimes
discouraged. Here we re-emphasize the beneficial role of the CD4+ T cell.
Experiments were performed with RSV-infected nude mice that received CD4+ T cells
by adoptive transfer. Data demonstrated that CD4+ T cells were necessary for the
induction of mucosal and systemic RSV-specific antibodies, for the establishment
of RSV-specific IgG and IgA antibody secreting cells in the upper and lower
respiratory tract, and for RSV clearance.
PMID- 28410813
TI - Post-hoc analysis of a randomized controlled trial: Diabetes mellitus modifies
the efficacy of the 13-valent pneumococcal conjugate vaccine in elderly.
AB - BACKGROUND: The 13-valent pneumococcal conjugate-vaccine (PCV13) was effective in
preventing vaccine-type Community-Acquired Pneumonia (VT-CAP) and Invasive
Pneumococcal Disease (VT-IPD) in elderly subjects, but vaccine efficacy (VE) in
patients with comorbidities at time of vaccination is unknown. METHODS: This is a
post hoc analysis of the CAPiTA study, a double blind, randomized controlled
trial with 84,496 immunocompetent participants aged ?65years, receiving PCV13 or
placebo vaccination. Presence of diabetes mellitus (DM), heart disease,
respiratory disease, liver disease, asplenia, and smoking at the time of
immunization was verified on medical records in 139 subjects developing the
primary endpoint of VT-CAP. Presence of DM and respiratory disease based on
International Classification of Primary Care (ICPC) coding was also determined in
40,427 subjects. FINDINGS: In the 139 subjects developing VT-CAP, DM caused
significant effect modification (p-value 0.002), yielding VE of 89.5% (95%CI,
65.5-96.8) and 24.7% (95%CI, -10.4 to 48.7) for those with and without DM,
respectively. Comparable effect modification (p-value 0.020) was found in the
40,427 subjects with and without ICPC-based classification of DM with VE of 85.6%
(95%CI, 36.7-96.7) and of 7.0% (95%CI, -58.5 to 45.5) respectively. Effect
modification through respiratory disease was not statistically significant,
although the point estimate of VE was lower for those with respiratory disease in
both analyses. There was no evidence of effect modification in subjects
stratified by heart disease, smoking, and presence of any comorbidity.
CONCLUSIONS: Among immunocompetent elderly, VE of PCV13 was modified by DM with
higher VE among subjects with DM. Significant effect modification was not
observed for subjects with heart disease, respiratory disease, smoking, or
presence of any comorbidity. CAPiTA trial registration number:
www.ClinicalTrials.gov; trial number NCT00744263.
PMID- 28410814
TI - The effects of convenience and quality on the demand for vaccination: Results
from a discrete choice experiment.
AB - BACKGROUND: Vaccination is an effective way to prevent infectious diseases. Most
studies analysed people's vaccine decisions, but few studies have analysed the
effects of convenience such as immunisation schedule and distance and the quality
of vaccination service on vaccination uptake. OBJECTIVE: The aim of this paper
was to investigate adults' preferences for convenience and quality of vaccination
service, calculate the private economic benefit from convenience (vaccination
schedule and distance) and quality, and predict the uptake rate for different
vaccine scenarios. METHODS: In our study, we interviewed 266 adults in 2 counties
of Shandong province in China. The discrete choice experiment (DCE) was employed
to analyse the preference for hepatitis B virus (HBV) vaccination, and a mixed
logit model was used to estimate respondent preferences for vaccination
attributes included in the DCE. RESULTS: The protection rate against hepatitis B
(HB), duration of protection, risk of side effects, vaccination cost, schedule,
and vaccination sites were proved to influence adults' preferences for HBV
vaccination. The estimated willingness to pay (WTP) for 1 dose schedule instead
of 3 doses and for a third-level vaccination site instead of a first-level site
was almost equal (19 RMB). However, if the protection duration of the vaccination
programme changed from 5years to 20years, the adults were willing to pay 35.05
RMB, and WTP for a 99% protection rate instead of a 79% rate was 67.71 RMB. The
predicted uptake rate is almost 43% for the base case of HBV vaccination.
CONCLUSIONS: Adults made trade-offs between vaccination schedules, vaccination
sites, and other characteristics of HBV vaccine. The impact of attributes of the
vaccine itself, especially protection rate against HB, duration of protection,
and risk of side-effects, is more dramatic than convenience and quality of
vaccination service.
PMID- 28410815
TI - Advancing new vaccines against pandemic influenza in low-resource countries.
AB - With the support of the Biomedical Advanced Research and Development Authority
(BARDA), PATH is working with governments and vaccine manufacturers to strengthen
their influenza vaccine manufacturing capacity and improve their ability to
respond to emerging pandemic influenza viruses. Vaccines directed against
influenza A/H5N1 and A/H7N9 strains are a particular focus, given the potential
for these viruses to acquire properties that may lead to a pandemic. This paper
will review influenza vaccine development from a developing country perspective
and PATH's support of this effort. Several vaccines are currently in preclinical
and clinical development at our partners for seasonal and pandemic influenza in
Vietnam (IVAC and VABIOTECH), Serbia (Torlak), China (BCHT), Brazil (Butantan),
and India (SII). Products in development include split, whole-virus inactivated
and live attenuated influenza vaccines (LAIVs). Additionally, while most
manufacturers propagate the virus in eggs, PATH is supporting the development of
cell-based processes that could substantially increase global manufacturing
capacity and flexibility. We review recent data from clinical trials of pandemic
influenza vaccines manufactured in developing countries. An important discussion
is on the role of whole virion vaccines for H5N1, given the poor immunogenicity
of split vaccines and the complexity involved in developing potent adjuvants.
PMID- 28410816
TI - The Pneumocell-study: Vaccination of IgG1- and IgG2-deficient patients with
Prevnar13.
AB - BACKGROUND: Patients with IgG-deficiency often suffer from repeated bacterial
infections with S. pneumoniae. Since there is a lack of knowledge regarding
whether IgG-deficient patients would benefit from conjugate pneumococcal
vaccination, we set out to evaluate the effect of Prevnar13 vaccination in IgG1-
and/or IgG2-deficient patients. METHOD: We designed a small pilot-study including
IgG1- and/or IgG2-deficient patients (n=10) and age- and sex-matched healthy
controls (n=10). Serum, plasma and heparin-blood were collected prior to
vaccination, as well as 1, 2 and 4weeks post vaccination, and the levels of
opsonophagocytic activity (Opa) titers and anti-pneumococcal IgG-antibodies were
analyzed. RESULTS: Patients generally had lower Opa-titers than controls for most
serotypes, but they exhibited an almost normal vaccine response to serotypes 6A
and 6B. Notably, 5/10 patients showed vaccine-response to at least one serotype.
Most patients reached the presumably protective levels of Opa-titers >=8 and anti
pneumococcal IgG levels of 0.35ug/ml by 4weeks post-vaccination for a majority of
the serotypes. CONCLUSION: Our results show that vaccination of IgG-deficient
patients with Prevnar13 is likely to have a clinical benefit. Our initial
findings will provide a framework for future vaccine-trials in this vulnerable
patient group. Registered at www.clinicaltrials.gov as NCT01847781.
PMID- 28410817
TI - Medication adherence and persistence over time with self-administered TNF-alpha
inhibitors among young adult, middle-aged, and older patients with rheumatologic
conditions.
AB - OBJECTIVE: Self-injectable TNF inhibitors are increasingly used early in the
chronic treatment of moderate to severe rheumatologic conditions. We estimated
medication adherence/persistence over time following initiation in young adult
and older adult patients with rheumatoid arthritis, ankylosing spondylitis or
psoriatic arthritis. METHODS: We conducted a retrospective cohort study of
patients aged 18+ years newly initiating etanercept, adalimumab, certolizumab
pegol, or golimumab using the Truven Health MarketScan Database between 2009 and
2013. Pharmacy dispensing data were used to calculate 12-month medication
possession ratios (MPR) and determine adherence (MPR >= 0.80) for up to 3 years
after starting therapy. Persistence over each 12-month interval was defined as
not having a >=92-day treatment gap. Multivariable generalized estimating
equation models were used to calculate odds ratios (OR) and robust 95% confidence
intervals (CI) for associations between patient characteristics and repeated
adherence/persistence measures over time. RESULTS: Among 53,477 new users, 14%
were young adults (18-34 years), 49% middle-aged (35-54 years), and 37% older
adults (55+ years). Overall, 37% of patients were adherent and 83% were
persistent in the first year of therapy. The lowest adherence (17%) and
persistence (70%) were observed among young adult patients by Year +3. Compared
to older adults, middle-aged (OR = 0.73, 95% CI: 0.71-0.76) and young adults (OR
= 0.50, 95% CI: 0.47-0.53) were less likely to be adherent. Higher Charlson
comorbidity scores, hospitalizations, and emergency department visits were
associated with non-adherence/non-persistence. CONCLUSIONS: We observed low
adherence to self-administered TNF inhibitors but most patients remained
persistent over time. Further efforts to improve adherence in young adults and
patients with greater comorbidity are needed.
PMID- 28410818
TI - [Use of protocol and evaluation of postoperative residual curarization incidence
in the absence of intraoperative acceleromyography - Randomized clinical trial].
AB - OBJECTIVE: Evaluate the incidence of postoperative residual curarization (PORC)
in the post-anesthesia care unit (PACU) after the use of protocol and absence of
intraoperative acceleromyography (AMG). METHODS: Randomized clinical trial with
122 patients allocated into two groups (protocol and control). Protocol group
received initial and additional doses of rocuronium (0.6mg.kg-1 and 10mg,
respectively); the use of rocuronium was avoided in the final 45minutes; blockade
reversal with neostigmine (50MUg.kg-1); time >= 15minutes between reversion and
extubation. CONTROL: initial and additional doses of rocuronium, blockade
reversal, neostigmine dose, and extubation time, all at the discretion of the
anesthesiologist. AMG was used in the PACU and PORC considered at T4/T1
ratio<1.0. RESULTS: The incidence of PORC was lower in protocol group than in
control group (25% vs. 45.2%, p=0.02). In control group, total dose of rocuronium
was higher in patients with PORC than without PORC (0.43 vs. 0.35mg.kg-1.h-1,
p=0.03) and the time interval between the last administration of rocuronium and
neostigmine was lower (75.0 vs. 101.0min, p<0.01). In protocol group, there was
no difference regarding the analyzed parameters (with PORC vs. without PORC).
Considering the entire study population and the presence or absence of PORC,
total dose of rocuronium was higher in patients with PORC (0.42 vs. 0.31mg.kg-1.h
1, p=0.01), while the time interval between the last administration of rocuronium
and neostigmine was lower (72.5 vs. 99.0min, p <= 0.01). CONCLUSION: The proposed
systematization reduced PORC incidence in PACU in the absence of intraoperative
AMG.
PMID- 28410819
TI - [Remifentanil does not increase urine output during oral surgery, contrary to its
effect during other surgeries - a cohort study].
AB - BACKGROUND: An increase in urine output by remifentanil injection during
laparoscopic procedures and surgeries such as cardiac and gynecological
procedures, due to suppression of the stress response to surgery, has been
reported. The aim of our prospective, observational, cohort study was to assess
the effect of remifentanil analgesia on urine output during dental and minor oral
surgery by comparing intraoperative urine output under defined infusion volumes
with and without the use of remifentanil. METHODS: Dental patients aged 16 years
or older, American Society of Anesthesiologists physical status 1, with no renal
diseases or abnormal blood values of serum creatinine and BUN, not on treatment
with diuretic drugs, and undergoing minor oro-maxillofacial surgery or dental
treatment under inhalation general anesthesia were included in this study.
Urethral catheterization was performed after anesthesia induction, and urine
output was measured every 30minutes. We measured urine volume (mL) and rate of
urine output (mL.kg-1.h-1) intraoperatively, and compared these parameters
between patients who did and did not receive remifentanil during the
intraoperative period. RESULTS: Eighty-seven patients were categorized into the
remifentanil group (n=43) or remifentanil non-use group (n=44). Both volume of
urine (mL) and rate of urine output (mL.kg-1.h-1) were not significantly
different between the two groups (remifentanil group, 372.3+/-273.5mL, 1.8+/
1.1mL.kg-1.h-1; remifentanil non-use group, 343.3+/-283.3mL, 1.9+/-1.2mL.kg-1.h
1; p=0.63; 0.57). CONCLUSION: Our results show that use of remifentanil during
dental and minor oral surgeries does not increase urine output.
PMID- 28410820
TI - [Optimizing post-operative pain management in Latin America].
AB - Post-operative pain management is a significant problem in clinical practice in
Latin America. Insufficient or inappropriate pain management is in large part due
to insufficient knowledge, attitudes and education, and poor communications at
various levels. In addition, the lack of awareness of the availability and
importance of clear policies and guidelines for recording pain intensity, the use
of specific analgesics and the proper approach to patient education have led to
the consistent under-treatment of pain management in the region. However, these
problems are not insurmountable and can be addressed at both the provider and
patient level. Robust policies and guidelines can help insure continuity of care
and reduce unnecessary variations in practice. The objective of this paper is to
call attention to the problems associated with Acute Post-Operative Pain (APOP)
and to suggest recommendations for their solutions in Latin America. A group of
experts on anesthesiology, surgery and pain developed recommendations that will
lead to more efficient and effective pain management. It will be necessary to
change the knowledge and behavior of health professionals and patients, and to
obtain a commitment of policy makers. Success will depend on a positive attitude
and the commitment of each party through the development of policies, programs
and the promotion of a more efficient and effective system for the delivery of
APOP services as recommended by the authors of this paper. The writing group
believes that implementation of these recommendations should significantly
enhance efficient and effective post-operative pain management in Latin America.
PMID- 28410821
TI - [Analgesia Nociception Index for perioperative analgesia monitoring in spinal
surgery].
AB - BACKGROUND AND OBJECTIVES: The Analgesia Nociception Index is an index used to
measure the levels of pain, sympathetic system activity and heart rate
variability during general anesthesia. In our study, Analgesia Nociception Index
monitoring in two groups who had undergone spinal stabilization surgery and were
administered propofol-remifentanil (Total Intravenous Anesthesia) and sevoflurane
remifentanyl anesthesia was compared regarding its significance for prediction of
postoperative early pain. METHODS: BIS and Analgesia Nociception Index monitoring
were conducted in the patients together with standard monitoring. During
induction, fentanyl 2MUg.kg-1, propofol 2.5mg.kg-1 and rocuronium 0.6mg.kg-1 were
administered. During maintenance, 1.0 MAC sevoflurane+remifentanil 0.05-0.3MUg.kg
1.min-1 and propofol 50-150MUg.kg-1.min+remifentanil 0.05-0.3MUg.kg-1.min-1 were
administered in Group S and Group T, respectively. Hemodynamic parameters, BIS
and Analgesia Nociception Index values were recorded during surgery and 30min
postoperatively. Postoperative visual analog scale (VAS) values at 30minutes were
recorded. RESULTS: While no difference was found between mean Analgesia
Nociception Index at all times of measurement in both groups, Analgesia
Nociception Index measurements after administration of perioperative analgesic
drug were recorded to be significantly higher compared to baseline values in both
groups. There was correlation between mean values of Analgesia Nociception Index
and VAS after anesthesia. CONCLUSION: Analgesia Nociception Index is a valuable
parameter for monitoring of perioperative and postoperative analgesia. In spine
surgery, similar analgesia can be provided in both Total Intravenous Anesthesia
with remifentanil and sevoflurane administration. Analgesia Nociception Index is
efficient for prediction of the need for analgesia during the early postoperative
period, and therefore is the provision of patient comfort.
PMID- 28410823
TI - The case for performing pleural biopsies for the aetiological diagnosis of
exudates. Yes.
AB - Pleural biopsies are especially indicated in the following circumstances: a)
inconclusive pleural fluid analysis and negative sputum study, if adenosine
deaminase (ADA) levels are unavailable; b) suspected multi-resistant
tuberculosis; c) a need for differentiating tuberculous pleurisy (if it
progresses with neutrophilia) and complicated parapneumonic effusion; d)
malignant pleural effusion coexisting with very high ADA levels; e) effusion
coexisting with lung cancer and negative pleural cytology; f) suspected
mesothelioma; and g) need for implementing re-treatment for patients with relapse
after chemotherapy. Image-guided needle biopsy is recommended for cases a and b,
while thoracoscopy is preferable for the other cases.
PMID- 28410822
TI - Diagnostic validity of hand gestures in chest pain of coronary origin.
AB - OBJECTIVES: To determine the frequency of 3 hand gestures by patients with chest
pain and determine the diagnostic validity of the gestures in acute coronary
syndrome. PATIENTS AND METHODS: A prospective study was conducted on 383 adult
patients treated for chest pain in an emergency department. We observed certain
hand gestures, previously referred to in the medical literature as characteristic
of coronary pain (gesture 1: a clenched fist held over the sternal area or
Levine's sign; gesture 2: open hand located over the same area; gesture 3: both
hands placed in the centre of the chest), as well as other gestures. We analysed
their association with the coronary origin of the pain. RESULTS: We confirmed the
coronary origin of the pain in 164 (43%) patients (ACS group). The other 219
patients (57%) did not have a coronary origin for the pain (nonACS group). Eighty
nine percent of the patients identified their pain with one of the 3 classical
gestures. The most frequent gesture was number 2, both overall (59%) and by group
(60% ACS group; 57.5% nonACS group). There was no significant association between
the type of gesture and the final diagnosis (P=.172). The greater specificity
corresponded to Levine's sign (90%), followed by other gestures (86%) and gesture
3 (81%). CONCLUSIONS: Although 89% of the patients expressed their chest pain
with one of the 3 manual gestures classically associated with coronary pain, none
achieved sufficient diagnostic accuracy to be used as indicative of this type of
pain.
PMID- 28410824
TI - Treated-and-released urinary catheterization in the emergency department by sex.
AB - BACKGROUND: The prevalence and difference in likely indications of urinary
catheterization (UC) in treated-and-released emergency department (ED) visits
between men and women are currently unknown. METHODS: This was a cross-sectional
analysis using the 2013 National Emergency Department Sample for all treated-and
released visits in persons aged >=18 years. The prevalence of conditions
associated with UC visits in men and women were identified. A hierarchical
ranking was used to categorize diagnosis codes identified during ED visits into
clinically meaningful categories to assess conditions for UC. RESULTS: In 2013,
there were 87,797,062 treated-and-released ED visits in adults. The rate of UC in
treated-and-released ED visits in adults was 4.3 per 1,000 visits, with 6.5 per
1,000 visits in men and 2.7 per 1,000 visits in women. Using the hierarchal
ranking, a higher proportion of UC visits in men were coded for acute urinary
retention, and a higher proportion of UC visits in women were coded for
neurologic, cognitive, and psychiatric conditions. CONCLUSIONS: The rate of UC in
treated-and-released ED visits was higher in men than women, and UC rate
increased with age. The heterogeneity of conditions coded in UC visits in women
compared with men may suggest more potentially avoidable UC in women in the
treated-and-released ED population. If confirmed, this would suggest
opportunities for quality improvement in the ED to prevent overutilization of
urinary catheters.
PMID- 28410826
TI - Crimean-Congo hemorrhagic fever: A neglected infectious disease with potential
nosocomial infection threat.
PMID- 28410825
TI - Active offer of vaccinations during hospitalization improves coverage among
splenectomized patients: An Italian experience.
AB - In 2014, an Italian hospital implemented a protocol for pneumococcal,
meningococcal, and Haemophilus influenzae type b vaccines offer to splenectomized
patients during their hospitalization. After 1 year, coverage for recommended
vaccinations increased from 5.7%-66.7% and the average time between splenectomy
and vaccines administration decreased from 84.7-7.5 days.
PMID- 28410827
TI - Staphylococcus aureus surface contamination of mobile phones and presence of
genetically identical strains on the hands of nursing personnel.
AB - We investigated the genetic relatedness of Staphylococcus aureus isolates
recovered from mobile phones and palms and fingers of users. Genetically
identical isolates were detected from mobile phones and their user and multiple
users, which is consistent with mobile phones serving as reservoirs of infection
in the health care environment. These findings reinforce the need for hand
hygiene prior to patient contact as the most effective intervention for
preventing health care-associated infection.
PMID- 28410828
TI - Early onset symptomatic neuropathy in a child with Type 1 Diabetes mellitus.
AB - Diabetic neuropathy (DN) is a major complication of Type 1 Diabetes Mellitus
(T1DM). It is usually subclinical in childhood, but can cause significant
impairment with its progression through to adulthood. Current guidelines vary in
their recommendation regarding screening for DN in children with T1DM, with some
advocating starting screening 5 years after the diagnosis of T1DM. Clinical
assessment comprising of history and neurological examination is the most
commonly used method for screening, though Nerve Conduction Studies (NCS) provide
better sensitivity in picking up early subclinical diabetic neuropathy. We
describe an adolescent female with poorly controlled T1DM, presenting with
symptomatic diabetic neuropathy within 2 years of disease onset and as the
initial long term complication. Thus, guidelines regarding screening for DN may
need revision, to start screening earlier than presently recommended, and NCS
could play a prominent role in screening children with significant risk factors
for developing DN.
PMID- 28410829
TI - Metabolic syndrome among HIV infected patients: A comparative cross sectional
study in northwestern Nigeria.
AB - INTRODUCTION: The increasing availability of antiretroviral drugs has made HIV
positive patients to live longer, and conditions that are associated with
longevity such as metabolic syndrome and other cardiovascular related conditions
have become relevant in them. This is less well studied among African
populations. Therefore the study aimed at estimating and comparing the prevalence
of and associated risk factors for the metabolic syndrome (MS) among African HIV
infected patients. METHOD: In this comparative cross-sectional study, we analyzed
the data of 300 participants matched for age and gender who satisfied the
inclusion criteria with half of the subjects on HAART, while the other half was
HAART naive. The MS was diagnosed using ATP-III criteria. RESULTS: The mean age
of the patients was 34.8+/-9.9years. The majority of the patients were females
64%. The prevalence of MS among HAART-exposed patients was found to be 19.3%,
while it was 5.3% among HAART naive patients (p=0.001). Raised triglyceride and
elevated blood pressure were the criteria with the highest occurrence among HAART
exposed, 82.8% for each. Advanced age, longer duration of HIV diagnosis and HAART
exposure, increased BMI, weight gain after HAART exposure, exposure to PIs and
increased mean CD4 cell count were found to be significantly associated with MS
(p<0.05). However, only age (OR 4.3, 95% CI 1.6-11.8, p=0.005) and BMI (OR 4.2,
95% CI 1.5-11.9, p=0.007) were found to be independently associated with the
development of MS. CONCLUSION: Exposure to HAART particularly protease inhibitor
based regimen increases the risk of MS among HIV-infected patients.
PMID- 28410830
TI - ?
PMID- 28410831
TI - Feasibility and Efficacy of Presurgical Exercise in Survivors of Rectal Cancer
Scheduled to Receive Curative Resection.
AB - BACKGROUND: Localized rectal carcinoma is invasive, with surgical resection the
standard treatment. The aim of this study was to determine the feasibility of a
supervised presurgical exercise intervention in patients with rectal cancer prior
to rectal resection. PATIENTS AND METHODS: Twelve patients volunteered to
undertake twice-weekly aerobic and resistance exercise for ~16 weeks prior to
surgery. At baseline, presurgery, and ~8 weeks postsurgery, muscle strength and
physical performance, body composition, quality of life, and fatigue were
assessed. RESULTS: Ten patients completed training, with 80% completing more than
one-half of the exercise sessions. Muscle strength improved 9% to 29% at
presurgery, although this was not statistically significant, and declined
postsurgery (P < .05). Importantly, postsurgery strength levels were comparable
with pretraining levels. Lean mass was preserved at presurgery despite
neoadjuvant chemoradiation treatment, whereas postsurgery lean mass decreased (P
< .05) compared with baseline (-3.2 +/- 5.4 kg) and presurgery (-3.7 +/- 5.4 kg).
There were no substantial changes in quality of life or fatigue. CONCLUSION:
Presurgical exercise is feasible, leading to modest improvements in some outcomes
despite chemoradiation treatment. The detrimental effects of surgery were
evident, especially in relation to lean mass. As such, exercise may facilitate
recovery by enhancing presurgery physical reserve capacity, thereby providing a
buffer to declines following surgery.
PMID- 28410832
TI - A Dose-finding and Biomarker Evaluation Phase Ib Study of Everolimus in
Association With 5-Fluorouracil and Pelvic Radiotherapy as Neoadjuvant Treatment
of Locally Advanced Rectal Cancer (E-LARC Study).
AB - BACKGROUND: During the past 20 years, considerable improvement has occurred in
the treatment of patients with locally advanced rectal cancer (LARC). With the
introduction of multimodal treatment, refinements in preclinical staging and
improvements in surgical skills, local relapse is no longer the major problem for
patients with LARC. However, many patients die of metastatic disease. The present
phase Ib study aimed to establish the maximum tolerated dose of everolimus
combined with 5-fluorouracil and radiotherapy in patients with LARC. PATIENTS AND
METHODS: Patients were sequentially assigned to 4 cohorts with an increasing dose
of everolimus, starting from 14 days before 5-fluorouracil and radiotherapy and
continuing throughout concomitant treatment. The secondary endpoints were the
Dworak tumor regression grade, pathologic complete response rate, neoadjuvant
rectal score, biomarker assessment (phosphorylated mTOR [mammalian target of
rapamycin] protein and phosphorylated-p70S6K protein). RESULTS: At the time of
this report, 12 patients had been treated, and no dose-limiting toxicity was
recorded. The most frequently reported acute toxicities were rectal tenesmus,
skin rash, diarrhea, and dysuria. All 12 patients underwent curative R0
resection. Two patients had Dworak tumor regression grade 4 (pathologic complete
response). No everolimus-related postoperative complications were observed. No
relationship was found between biomarker expression and the clinicopathologic
outcomes. CONCLUSION: Although the addition of everolimus did not appear to
worsen the toxicity of chemoradiation in patients with LARC, evaluation of its
activity deserves further investigation in larger clinical trials.
PMID- 28410833
TI - Boberg et al. (2011) - Corrigendum (2016): Further significant modifications
needed.
PMID- 28410834
TI - Wearing ID Badges in the Operating Room Environment: Is Reconsideration
Warranted?
AB - BACKGROUND: Surgical site infection and nosocomial infections in general have
appropriately undergone increased scrutiny over the last decade. Numerous studies
have documented pathogenic bacterial contamination of personal items such as cell
phones, pagers, ties, and pens in the hospital setting. It is our understanding
that Joint Commission on Accreditation of Healthcare Organizations requires all
personnel to wear an identification badge at all times, which includes the
operating room environment. METHODS: Badges, lanyards, and pagers from operating
room personnel were swabbed and cultured using the same protocol used for
surgical specimens in the operating rooms. Personnel included orthopedic
attendings (14), orthopedic residents (20), nurses (19), and anesthesia personnel
(11). RESULTS: A total of 64 badges were sampled, with no methicillin-sensitive
Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) cultured
on any of the badges. Two of 64 had enterococcus (3%), and 1 of those was
vancomycin resistant. Pagers had similar results, with only 1/42 growing MSSA or
enterococcus (2.4%), and no MRSA. Lanyards showed higher rates of contamination.
There were 11% with MSSA or MRSA out of 27 sampled. Highest contamination rates
were with orthopedic staff and resident lanyards, with 3/22 (13.6%) growing MSSA
or MRSA. No lanyards grew enterococcus. When comparing rates of MSSA and/or MRSA
between groups, lanyards had a statistically significant higher rate (P < .05).
CONCLUSION: At a minimum, operating room personnel should probably not use
lanyards to display their ID badges.
PMID- 28410835
TI - Modified Extended Trochanteric Osteotomy for the Treatment of Vancouver B2/B3
Periprosthetic Fractures of the Femur.
AB - BACKGROUND: Femoral component revision is the treatment of choice for Vancouver
type B2/B3 periprosthetic femur fractures (PFFs). The purpose of this study was
to report the clinical outcome of revision total hip arthroplasty with the use of
a modified extended trochanteric osteotomy (ETO) in PFF treatment. METHODS: A
total of 43 cases between 2000 and 2014 were analyzed. Clinical and radiographic
evaluation was performed with a mean follow-up of 40 months. Patient survival
after revision surgery, complications, radiographic outcomes, and quality of life
and hip function were assessed. RESULTS: Merle d'Aubigne and Postel score
averaged 15, and mean postoperative Harris hip score was 70. Radiographic
evaluation revealed that the ETO and fractures healed in all but 1 patient within
9 months. Component stability and apparent osseointegration were not coincident
with healing of the osteotomy and fracture sites proximal to the inserted stem.
Six patients (15%) developed postoperative complications, which included the
following: 1 nonunion with progressive subsidence, 2 hip dislocations, 2 deep
infections, and 1 breakage of the modular junction of the revision stem.
CONCLUSION: The modified ETO with a lateral approach to the hip for the treatment
of PFF is compatible with fracture healing, a low dislocation rate, and good
clinical results. However, component stability and apparent osseointegration are
coincident with fracture healing only in the distal aspect of the inserted stem.
Absence of proximal osseointegration might lead to poor osseous support resulting
in inadequate fatigue strength at the junction of the dual modular revision stem.
PMID- 28410836
TI - Low Preoperative BMD Is Related to High Migration of Tibia Components in
Uncemented TKA-92 Patients in a Combined DEXA and RSA Study With 2-Year Follow
Up.
AB - BACKGROUND: The fixation of uncemented tibia components in total knee
arthroplasty may rely on the bone quality of the tibia; however, no previous
studies have shown convincing objective proof of this. Component migration is
relevant as it has been shown to predict aseptic loosening. METHODS: We performed
2-year follow-up of 92 patients who underwent total knee arthroplasty surgery
with an uncemented tibia component. Bone mineral density (BMD; g/cm2) of the
tibia host bone was measured preoperatively using dual energy X-ray
absorptiometry. The proximal tibia was divided into 2 regions of interest (ROI)
in the part of the tibia bone where the components were implanted.
Radiostereometric analysis was performed postoperatively and after 3, 6, 12, and
24 months. The primary outcome was maximum total point motion (MTPM; mm).
Regression analysis was performed to evaluate the relation between preoperative
BMD and MTPM. RESULTS: We found low preoperative BMD in ROI1 to be significantly
related to high MTPM at all follow-ups: after 3 months (R2 = 20%, PBMD = 0.017),
6 months (R2 = 29%, PBMD = 0.003), 12 months (R2 = 33%, PBMD = 0.001), and 24
months (R2 = 27%, PBMD = 0.001). We also found a significant relation for low BMD
in ROI2 and high MTPM: 3 months (R2 = 19%, PBMD = 0.042), 6 months (R2 = 28%,
PBMD = 0.04), 12 months (R2 = 32%, PBMD = 0.004), and 24 months (R2 = 24%, PBMD =
0.005). CONCLUSION: Low preoperative BMD in the tibia is related to high MTPM.
Thus, high migration of uncemented tibia components is to be expected in patients
with poor bone quality.
PMID- 28410837
TI - Diurnal salivary cortisol levels and slopes in a community sample of healthy
adults: Is current research conclusive?
PMID- 28410838
TI - Reply to the commentary by Parrot and Downey (2017).
PMID- 28410839
TI - New technique for midpalatal osteotomy in surgically-assisted rapid palatal
expansion.
PMID- 28410840
TI - Bilateral submandibular rhabdomyomas: case report.
PMID- 28410841
TI - Contemporary surgical management of hypodontia.
AB - Hypodontia is the term most commonly applied to the condition in which teeth
congenitally fail to develop. Such cases differ from teeth that have been lost
early or that have failed to erupt, although their initial presentation may be
similar and therefore not recognised. The range of missing teeth and their
physical and psychological results is large, and the difference in complexity in
the management of a patient with isolated hypodontia compared with one with
oligodontia or anodontia together with skeletal and orthognathic discrepancies
should not be underestimated. Surgical interventions primarily involve
augmentation of bone before placement of an implant, but may include techniques
such as distraction osteogenesis and orthognathic surgery. These patients are
best managed by a multidisciplinary team, and in this review our aim has been to
describe the role of oral and maxillofacial surgeons within it.
PMID- 28410842
TI - Evidence of impaired microvascular dilatation in preterms with acute respiratory
distress syndrome.
AB - BACKGROUND: Evaluating microcirculatory function in severely ill neonates is a
relevant, unmet clinical need. Inappropriate peripheral microvascular
vasodilatation is thought to contribute to cardiovascular alterations in preterm
infants with acute respiratory distress syndrome (ARDS). We directly evaluated
microcirculatory function in preterms with ARDS. METHODS: Peripheral
microvascular function was assessed in 50 newborns, divided in three groups:
preterms with ARDS; at-term newborns with mild-moderate congenital cardiac
disease (Cardio group); healthy controls. Skin microvascular perfusion was
assessed using an operator-independent, laser-Doppler camera, under basal
conditions and during post-ischemic hyperemia, allowing objective quantification
of microcirculatory flow reserve (MFR). RESULTS: At baseline, perfusion was
similar among the three groups. During post-ischemic phase, microcirculatory
perfusion significantly increased in controls compared to baseline (baseline
perfusion units [PU] 3.65+/-1.8 to 4.59+/-2.1 during hyperemia; p for
trend=0.041), whereas in ARDS group perfusion tended to decrease. Comparing
results across groups, ARDS showed lower values compared to either controls or
Cardio groups (p<0.05). Controls, and to a lesser extent Cardio group, showed
recruitable MFR (1.78+/-1.13 and 1.19+/-0.30 in controls and Cardio group,
respectively). MFR was absent in ARDS (0.88+/-0.48; p<0.05), documenting impaired
microcirculatory response. CONCLUSION: We demonstrate that it is possible to
assess, non-invasively and quantitatively, vasodilator response of skin
microcirculation to physiological stimuli in neonates. We also documented that
microvascular vasodilation is impaired in preterms with ARDS.
PMID- 28410843
TI - Left ventricular hypertrophy does not prevent heart failure in experimental
hypertension.
AB - BACKGROUND: Left ventricular hypertrophy (LVH) secondary to hypertension has been
accepted to prevent heart failure (HF) while paradoxically increasing
cardiovascular morbi-mortality. OBJECTIVES: To evaluate whether antihypertensive
treatment inhibits LVH, restores beta-adrenergic response and affects myocardial
oxidative metabolism. METHODS: Ninety spontaneously hypertensive rats (SHR) were
distributed into groups and treated (mg/kg, p.o.) with: losartan 30 (L),
hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C). Hypertension control
group comprised 18 normotensive rats (Wistar-Kyoto, WKY). Following euthanasia at
16months, contractility was measured in 50% of rats (Langendorff system) before
and after isoproterenol (Iso) 10-9M, 10-7M and 10-5M stimulation. Left
ventricular weight (LVW) was measured in the remaining hearts, and normalized by
BW. Expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2), glutaredoxin 3
(Grx-3), caspase-3 and brain natriuretic peptide (BNP) was determined. RESULTS:
Systolic blood pressure (mmHg): 154+/-3 (L), 137+/-1 (H), 190+/-3 (R)*, 206+/-3
(SHR)*, 183+/-1 (C)**, and 141+/-1 (WKY) (*p<0.05 vs. L, H, WKY, **p<0.05 vs. L,
H, WKY, SHR). LVW/BW was higher in SHR and R (p<0.05). Groups SHR, R and C
evidenced baseline contractile depression. Response to Iso 10-5M was similar in
WKY and L. Expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L
(p<0.01). CONCLUSIONS: Present findings argue against the traditional idea and
support that LVH might not be required to prevent HF. Increased expression of
thioredoxins by antihypertensive treatment might be involved in protection from
HF.
PMID- 28410844
TI - Folate Receptor Alpha Expression Is Associated With Increased Risk of Recurrence
in Triple-negative Breast Cancer.
AB - BACKGROUND: Folate receptor alpha (FOLR1) has been identified as a potential
prognostic and therapeutic target in breast cancer. The limited studies
evaluating the role of FOLR1 in breast cancer have shown that FOLR1 protein
expression is enriched in triple-negative breast cancer (TNBC) and associated
with poor prognosis in all breast cancer types. Newly developed anti-FOLR1
therapy could potentially be used in patients with TNBC for whom few therapeutic
options exist. We sought to evaluate FOLR1 protein expression in a cohort of
patients with TNBC to determine its prevalence and prognostic value. MATERIALS:
Immunohistochemistry was performed for FOLR1 in 76 cases of primary TNBC.
Membranous staining in >= 5% of cells was deemed positive in a given case.
Statistical analyses correlating FOLR1 protein expression with clinicopathologic
parameters and clinical outcome (disease-free survival and overall survival) were
performed. RESULTS: A total of 76 cases of primary TNBC were studied. Most cases
were negative for FOLR1 (80.3%; 61/76). FOLR1 expression did not correlate with
any clinicopathologic parameters. FOLR1 expression was significantly correlated
with decreased disease-free survival (hazard ratio, 2.61; 95% confidence
interval, 0.96-7.09; P = .0497 log-rank test). Although FOLR1 expression trended
towards decreased overall survival, it was not statistically significant (hazard
ratio, 1.99; 95% confidence interval, 0.62-6.36; P > .05 log-rank test).
CONCLUSION: We found a lower incidence of FOLR1 expression in TNBC compared with
other studies; however, these patients may benefit from anti-folate therapy as
other targeted therapies are not available. Although no correlation between FOLR1
expression and standard clinicopathologic parameters was identified, our findings
suggest that FOLR1 expression is prognostically significant in TNBC.
PMID- 28410845
TI - [Paraneoplastic hypoglycemia: The hopes of pathophysiological documentation].
AB - Doege-Potter syndrome is a paraneoplastic syndrome characterized by non-islet
cell tumor hypoglycemia secondary to a solitary fibrous tumor. These tumors are
rare and usually asymptomatic. The syndrome of hypoglycemia is seen in less than
5% of the cases, and the associated tumors are large with a high mitotic rate.
The cause of hypoglycemia is related to insulin-like growth factors produced by
these tumors called "big" IGF-2. Several biological tests can demonstrate the
increase of "big" IGF-2 plasma levels confirming the diagnosis of non-islet cell
tumor induced hypoglycemia. The diagnosis is suggested by imaging but diagnostic
confirmation is provided by the surgery, which remains the treatment of choice.
Resection in many cases is the cure leading to hypoglycemia resolution.
Recurrences and malignant transformations are possible which imposes a long-term
monitoring. We report a case with relapsed malignant pleural fibrous tumor for
which the pathophysiological mechanism of hypoglycemia could be documented as a
paraneoplastic syndrome.
PMID- 28410846
TI - Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in
the implementation of precision medicine.
AB - In the last decade, breakthroughs in technology have improved our understanding
of genomic, transcriptional, proteomic, epigenetic aberrations and immune
mechanisms in carcinogenesis. Genomics and model systems have enabled the
validation of novel therapeutic strategies. Based on these developments, in 2007,
we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer
Therapy) study, the first personalized medicine program for patients with
advanced cancer at The University of Texas MD Anderson Cancer Center. We
demonstrated that in patients referred for Phase I clinical trials, the use of
tumor molecular profiling and treatment with matched targeted therapy was
associated with encouraging rates of response, progression-free survival and
overall survival compared to non-matched therapy. We are currently conducting
IMPACT2, a randomized study evaluating molecular profiling and targeted agents in
patients with metastatic cancer. Optimization of innovative biomarker-driven
clinical trials that include targeted therapy and/or immunotherapeutic approaches
for carefully selected patients will accelerate the development of novel drugs
and the implementation of precision medicine.
PMID- 28410847
TI - Response to the letter to the Editor "Biodegradable airway stents in infants -
Potential life-threating pitfalls".
PMID- 28410848
TI - Improving Access to Image-guided Procedures at an Integrated Rural Critical
Access Hospital: Ultrasound-guided Thyroid Biopsy Program.
AB - PURPOSE: Critical access hospitals face difficulty providing all services locally
and may need to refer patients off-site for additional care. Providing on-site
minimally invasive biopsies, may obviate visits to tertiary or quaternary care
centers. This study aims to assess feasibility and outcomes of an ultrasound
guided thyroid biopsy program in a critical access hospital. METHODS: In this
HIPAA compliant, IRB approved study, the Interventional Radiology (IR) database
of a 19-bed, island, rural, critical access hospital without onsite pathology
services affiliated with our quaternary care institution was retrospectively
reviewed to identify all thyroid biopsies that were performed on site since
inception of the service in April 2014 through August 2016. A specialized biopsy
and specimen collection protocol was created as each specimen was transferred to
and analyzed by the pathology department at our affiliated quaternary care
institution. RESULTS: Two IR physicians carried out thyroid biopsies on 34
nodules in 29 patients during the study period. The mean age of patients was 56.5
+/- 14.0, with a range of 35-85 and 86% female, 14% male. 94.1% of nodules had
adequate material for interpretation on the first biopsy and 97.1% upon repeat
biopsy. Ultimately, 5 patients (with 6 nodules) underwent surgical resection at
the integrated quaternary care center. Surgical resection identified one atypical
follicular adenoma, one follicular variant of papillary thyroid carcinoma, two
papillary carcinomas, and two Hurthle cell tumors. CONCLUSION: IR thyroid biopsy
services may be successfully provided in the rural setting without onsite
pathology analysis and adequacy checks, enhancing patient access and streamlining
care while also expanding the reach of tertiary care centers.
PMID- 28410849
TI - Research Mentorship for Our Residents and Fellows: A Vital Supplement for the
Health of Our Specialty.
AB - In this article, we discuss the importance of mentorship in Radiology and more
specifically mentorship in Radiology research to help ensure the advancement of
our specialty. We also describe how research mentorship is conducted at our
institution.
PMID- 28410850
TI - Simultaneous analysis of nucleobases, nucleosides and ginsenosides in ginseng
extracts using supercritical fluid chromatography coupled with single quadrupole
mass spectrometry.
AB - Nucleobases, nucleosides and ginsenosides, which have a significant impact on the
physiological activity of organisms, are reported to be the active components of
ginseng, while they are less present in ginseng extracts. Few analytical methods
have been developed so far to simultaneously analyze these three classes of
compounds with different polarities present in ginseng extracts. In the present
study, a simple and efficient analytical method was successfully developed for
the simultaneous separation of 17 nucleobases, nucleosides and ginsenosides in
ginseng extracts using supercritical fluid chromatography coupled with single
quadrupole mass spectrometry (SFC-MS). The effect of various experimental factors
on the separation performance, such as the column type, temperature and
backpressure, the type of modifier and additive, and the concentration of make-up
solvent were systematically investigated. Under the selected conditions, the
developed method was successfully applied to the quality evaluation of 14 batches
of ginseng extracts from different origins. The results obtained for the
different batches indicate that this method could be employed for the quality
assessment of ginseng extracts.
PMID- 28410851
TI - Paediatric Laboratory Medicine - Some reflections on the sub-specialty.
PMID- 28410852
TI - Cefiderocol MIC quality control ranges in iron-depleted cation-adjusted Mueller
Hinton broth using a CLSI M23-A4 multi-laboratory study design.
AB - Cefiderocol (formerly S-649266) is a new catechol-substituted parenteral
siderophore cephalosporin with potent in vitro antibacterial activity against
Gram-negative isolates including multidrug-resistant strains. A recent study
following CLSI M23-A4 quality control guidelines established cefiderocol MIC QC
ranges against Escherichia coli ATCC 25922 (0.06-0.5 MUg/mL) and Pseudomonas
aeruginosa ATCC 27853 (0.06-0.5 MUg/mL).
PMID- 28410853
TI - Use of organism identification by 16S ribosomal RNA polymerase chain reaction to
shorten antimicrobial length of therapy.
AB - BACKGROUND: Organism detection by 16S ribosomal RNA (rRNA) PCR followed by
amplicon sequencing identification may help guide antimicrobial treatment in
culture-negative patients. The objectives of this study were to assess the effect
of a positive versus negative 16S rRNA PCR on antibiotic length of therapy (LOT)
and rate of antibiotic discontinuation. METHODS: Patients with a sterile site,
direct-specimen 16S rRNA PCR negative, and suspected active infection were
matched 1:1 with 16S rRNA PCR positive patients based on specimen site and
retrospectively evaluated. RESULTS: Ninety patients were included (n=45 positive
and negative). 16S rRNA PCR negative patients had shorter median LOT (33days [IQR
8-46] versus 43days [IQR 29-51], P=0.02). Antibiotics were discontinued more
frequently in 16S rRNA PCR negative patients (38% versus 4%, P<0.01).
CONCLUSIONS: For culture-negative patients with suspected sterile site infection,
a negative, direct-specimen 16S rRNA PCR may help discontinue antibiotics and
decrease LOT.
PMID- 28410854
TI - The correlation of serum bilirubin levels with disease activity in patients with
rheumatoid arthritis.
AB - BACKGROUND: We investigated the relationship between serum bilirubin and disease
activity in patients with rheumatoid arthritis (RA). METHODS: We included a total
of 173 consecutive RA patients without steroid treatment and 346 healthy
subjects; the disease activity score in 28 joints (DAS28) was used to assess
disease activity in patients with RA. RESULTS: Serum bilirubin concentrations
were significantly lower in RA patients than in controls. Serum bilirubin was
found to be negatively correlated with C-reactive protein (CRP) concentration and
erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in
patients with RA. There was a negative correlation between the serum bilirubin
and DAS28 score (r=-0.331, P<0.001). Serum bilirubin was independently associated
with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression
analysis. CONCLUSIONS: Serum bilirubin concentrations are lower in patients with
RA compared to controls and correlate with disease activity in patients with RA.
PMID- 28410855
TI - Methods of albumin estimation in clinical biochemistry: Past, present, and
future.
AB - Estimation of serum and urinary albumin is routinely performed in clinical
biochemistry laboratories. In the past, precipitation-based methods were popular
for estimation of human serum albumin (HSA). Currently, dye-binding or
immunochemical methods are widely practiced. Each of these methods has its
limitations. Research endeavors to overcome such limitations are on-going. The
current trends in methodological aspects of albumin estimation guiding the field
have not been reviewed. Therefore, it is the need of the hour to review several
aspects of albumin estimation. The present review focuses on the modern trends of
research from a conceptual point of view and gives an overview of recent
developments to offer the readers a comprehensive understanding of the subject.
PMID- 28410856
TI - Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy
Scores Over Time in Early Alzheimer Disease.
AB - OBJECTIVES: Apathy is among the earliest and most pervasive neuropsychiatric
symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates
with functional impairment and disease progression. We investigated the
association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in
cognitively normal, mild cognitive impairment, and AD dementia subjects from the
Alzheimer's Disease Neuroimaging Initiative database. DESIGN: Cross-sectional and
longitudinal studies. SETTING: 57 North American research sites. PARTICIPANTS:
402 community dwelling elders. MEASUREMENTS: Apathy was assessed using the
Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions
implicated in the neurobiology of apathy and AD was investigated in relationship
to apathy at baseline (cross-sectional general linear model) and longitudinally
(mixed random/fixed effect model). Covariates included age, sex, diagnosis,
apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant
use. RESULTS: Cross-sectional analysis revealed that posterior cingulate
hypometabolism, diagnosis, male sex, and antidepressant use were associated with
higher apathy scores. Longitudinal analysis revealed that the interaction of
supramarginal hypometabolism and time, posterior cingulate hypometabolism, and
antidepressant use were associated with higher apathy scores across time; only
supramarginal hypometabolism was positively related to rate of increase of
apathy. CONCLUSIONS: Results support an association of apathy with hypometabolism
in parietal regions commonly affected in early stages of AD, rather than medial
frontal regions implicated in the neurobiology of apathy in later stages. Further
work is needed to substantiate whether this localization is specific to apathy
rather than to disease stage, and to investigate the potential role of AD
proteinopathies in the pathogenesis of apathy.
PMID- 28410857
TI - Measuring Participant Effort in a Depression Prevention Trial: Who Engages in
Problem-Solving Therapy?
AB - OBJECTIVE: To determine the acceptability of clinical interventions for
depression prevention, identification of clinical characteristics associated with
intervention engagement is needed. The purpose of this study is to describe
levels and correlates of participant engagement in Problem Solving Therapy (PST)
in adults 60 and older with subthreshold depression. METHODS: As part of a
clinical trial to prevent depression among older adults with subthreshold
depression, participants who were randomized to receive PST completed 6-8
sessions in which they learned skills to solve self-selected problems that were
contributing to stress and reduced quality of life. To measure participants'
engagement with PST, interventionists completed 3 scales that rated participants'
level of participation in problem solving activities, understanding of the
multistep process of PST, and between-session homework effort. Using logistic
regression, we examined whether physical health, level of cognitive function,
gait speed, and disability served as correlates of engagement in the PST
intervention. RESULTS: Gait speed, a measure of physical and cognitive health,
was significantly associated with engagement in PST. Participants who walked
faster were more likely to engage with PST compared to participants who walked
more slowly. No other baseline variables were significant correlates.
CONCLUSIONS: Older adults who walk more slowly may need alternative delivery
methods to fully engage in PST. Gait speed reflects physical and cognitive
health, and predicts frailty, disability, and psychomotor speed slowing. For
these reasons, gait speed may be a marker for factors that will serve to predict
poorer engagement in psychosocial interventions like PST.
PMID- 28410858
TI - Prevalence of older in-patients at risk of clopidogrel resistance according to
the STIB score. Results from REPOSI registry.
PMID- 28410859
TI - Optic Nerve Hypoplasia: More Than Meets the Eye.
PMID- 28410860
TI - Comprehensive Screening for Suicide Risk in Primary Care.
AB - INTRODUCTION: Suicide is a major public health problem and a complex clinical
challenge. Assessment and early identification could be enhanced with screening
tools that look beyond depression. The purpose of this study was to identify
profiles of risk behaviors and social stress associated with suicidal ideation
and behavior using the Behavioral Health Screen. METHODS: The study used
screening data from 2,513 primary care patients (aged 14-24 years). Data were
collected between 2008 and 2012, and were analyzed in 2016. RESULTS: Latent class
analysis identified a high and low risk profile. Domains of primary influence
included substance use, sexual assault, same-sex behavior, and unsafe sex. The
high-risk group was 11 times more likely to have made a suicide attempt, five
times more likely to report a history of suicidal ideation and behavior, and
three times more likely to report recent suicidal ideation and behavior.
CONCLUSIONS: Risk behaviors and social stress contribute to the risk for suicide
above and beyond depression and should be assessed during routine primary care
visits with adolescents. The Behavioral Health Screen can screen all these
domains and thus assist primary care providers in assessing for both psychiatric
and social stress factors associated with youth suicide.
PMID- 28410861
TI - Prevalence of Cardiovascular Health by Occupation: A Cross-Sectional Analysis
Among U.S. Workers Aged >=45 Years.
AB - INTRODUCTION: Identification of groups with poor cardiovascular health (CVH) can
inform where and how to target public health efforts. National prevalence
estimates of CVH were derived for clinical (blood glucose, total cholesterol,
blood pressure) and behavioral (BMI, diet quality, physical activity, smoking)
factors among U.S. workers aged >=45 years. METHODS: This cross-sectional
analysis included 6,282 employed black and white men and women aged >=45 years
enrolled in the national population-based REasons for Geographic And Racial
Differences in Stroke study from 2003 to 2007. Each CVH factor was scored as
ideal (2); intermediate (1); or poor (0) according to American Heart Association
criteria, and summed to define optimal composite scores: CVH (sum, 10-14);
clinical (sum, 5-6); and behavioral (sum, 6-8) health. Occupational data were
collected 2011-2013. Analyses were conducted in 2016. RESULTS: Only 14% met ideal
criteria for all three clinical health factors, and none met ideal criteria for
all four behavioral health factors. Sales and low status office workers had a low
prevalence of optimal CVH. Service workers in protective services and the food
preparation and serving occupations had a low prevalence of optimal clinical
health; computer and healthcare support workers had a low prevalence of optimal
behavioral health. CONCLUSIONS: The prevalence of optimal CVH among middle-aged
and older workers in the U.S. is low, but considerable differences exist by
occupation. Targeted public health interventions may improve the CVH of at-risk
older workers with different clinical and behavioral risk factor profiles
employed in diverse occupational settings.
PMID- 28410862
TI - State-Level Awareness of Chronic Kidney Disease in the U.S.
AB - INTRODUCTION: This study examined state-level variation in chronic kidney disease
(CKD) awareness using national estimates of disease awareness among adults in the
U.S. with CKD. METHODS: Data on U.S. adults were obtained from two national,
population-based surveys: (1) the Behavioral Risk Factor Surveillance System
(BRFSS 2011; n=506,467), a state-level phone survey containing information on
self-reported kidney disease; and (2) the National Health and Nutrition
Examination Survey (NHANES 2005-2012; n=20,831), containing physical health
examination, surveys containing data on self-reported kidney disease, risk
factors, and laboratory values. CKD was defined as an estimated glomerular
filtration rate of 15-59 mL/minute/1.73 m2 or urinary albumin-to-creatinine ratio
>30 mg/g. As BRFSS does not include laboratory data, CKD status for each person
was imputed (multiple) based on a logistic regression model predicting NHANES CKD
status. CKD awareness in each state was estimated as the weighted proportion of
BRFSS participants with imputed CKD who reported having kidney disease. RESULTS:
Overall, estimated CKD awareness was 9.0% (95% CI=8.0%, 10.0%), ranging from 5.8%
(95% CI=4.8%, 6.8%) in Iowa to 11.7% (95% CI=9.7%, 13.7%) in Arizona. Awareness
was greater among adults with hypertension (12.0%) and diabetes (15.3%) than
among adults without those conditions, and lower in Hispanics (6.0%) than in non
Hispanic whites (8.8%), non-Hispanic blacks (9.9%), and other racial/ethnic
groups (12.7%). CONCLUSIONS: Among individuals with CKD, awareness of their
condition was very low and varied approximately twofold among states. This is the
first study to estimate awareness of kidney disease by state for the U.S. adult
population.
PMID- 28410863
TI - [Human papillomaviruses vaccination: Parental awareness and acceptance of the
vaccine for children in Lower Normandy schools and informative campaign during
the 2015-2016 school year].
AB - BACKGROUND: The vaccine against human papillomavirus (HPV) can be administered
starting at the age of 9 years. Parents thus play a major role in the choice of
vaccination. The objective of this study was to investigate parental awareness
about anti-HPV vaccination in Lower Normandy and to measure their vaccinal
intentions before an informative campaign. METHODS: The study population included
parents of children aged 10-11 years enrolled in school (2015-2016) in Lower
Normandy, France. The initial study was observational and descriptive. With the
agreement of the academic directors, 16 middle schools were selected. A
questionnaire was delivered to the school children and collected in September
2015 by the school nurses. RESULTS: Within the selected middle schools, 1427
questionnaires were delivered. School nurses collected 1168 questionnaires
(81.9%) among which 1155 could be analyzed because they contained answers
(80.9%). Out of 575 girls aged 10-11 years, 523 (91.0%) were not vaccinated
against HPV. Among parents of non-vaccinated schoolgirls who answered, 48.4% did
not know if they intended to have their children vaccinated (251 of 519
questionnaires). There was a significant association between the socio
professional status of the parents who answered and their intention to vaccinate
their daughters against HPV (P=0.03). Parents were significantly more likely to
immunize their children when they previously knew about the vaccine (P<0.001) and
when they had good knowledge about the vaccine (P<0.05). Parents who previously
had their daughters vaccinated were also significantly more likely to have their
sons vaccinated against HPV (P<0.001). CONCLUSION: The significant association
between knowledge about the vaccine and intentions to have their children
vaccinated allows us to predict the effectiveness of information campaigns on
vaccination rates.
PMID- 28410864
TI - [Prevalence of cardiovascular risk factors in urban and rural communities in the
Wilaya of Tlemcen (Algeria): A comparative study].
AB - BACKGROUND: In Algeria, few studies have been conducted to determine the
prevalence of genetic and environmental risk factors of cardiovascular diseases
as a function of residence. The objective of this study was therefore to
determine the prevalence of cardiovascular risk factors according to sex and age
in urban and rural communities in the Wilaya of Tlemcen (Algeria). MATERIAL AND
METHODS: A population survey was conducted on a representative sample of 864
individuals aged 20years and over, among inhabitants in urban and rural communes
in the Wilaya of Tlemcen. Each subject answered the questionnaire on
cardiovascular risk factors, underwent a physical examination and had a blood
sample drawn. RESULTS: The prevalence of hypercholesterolemia was 6.6%, it was
found to be higher in urban areas (8.4%) than in rural areas (4.6%). The
prevalence of low HDL cholesterol levels was higher in urban (28.8%) than rural
(23.9%) areas. The prevalence of family history of cardiovascular disease did not
differ between the two sexes and between urban (15.7%) and rural (14.0%) areas.
The prevalence of hypertension was higher in urban (28.0%) than in rural (16.8%)
areas, and was highest among women aged 65 years or older in urban areas (67.3%)
and in rural areas (66.6%). The prevalence of diabetes was higher among women
living in urban areas (21.4%) compared with rural areas (15.4%). Obesity was much
more frequent among women than among men in urban areas (24.7% in women and 9.5%
in men) and in rural areas (28.3% in women and 8.3% in men). The prevalence of
smoking was 45.8% for men and with no significant variations between urban areas
and rural areas. CONCLUSION: The prevalence of cardiovascular risk factors
according to sex and age in the two communes are high in two communes in the
Wilaya of Tlemcen. However, the prevalence of hypertension, hypercholesterolemia
and diabetes were higher in women in urban than in rural areas. This finding
focuses attention on the need for measures to reduce the prevalence of these
cardiovascular risk factors in these communities. Factors such as sex age and
area of residence are indicators to consider when targeting interventions.
PMID- 28410866
TI - Backward masking interrupts spatial attention, slows downstream processing, and
limits conscious perception.
AB - The attentional blink (AB) is a difficulty in correctly processing a target when
it follows one or more other targets after a short delay. When no backward mask
is presented after the last critical target, there is no or little behavioral AB
deficit. The mask plays an important role in limiting conscious access to target
information. In this electrophysiological study, we tested the impact of masking
on the deployment and engagement of attention by measuring the N2pc and P3
components in an RSVP paradigm. We found that the presence of a mask in an AB
paradigm reduced the amplitude of the N2pc, P3a, and P3b components. In addition
to reducing encoding in memory, masking also reduced the effectiveness of the
deployment and engagement of attention on the last target. We discuss the role of
these findings in the context of current masking, consciousness, and AB models.
PMID- 28410865
TI - Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma
Treated with Nivolumab in CheckMate 025.
AB - BACKGROUND: Response patterns to nivolumab differ from those seen with other
approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab
in previously treated patients with advanced renal cell carcinoma who were
treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression.
DESIGN, SETTING, AND PARTICIPANTS: This was a subgroup analysis of patients
treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to
tolerate therapy and exhibiting investigator-assessed clinical benefit were
eligible to be treated beyond RECIST progression (TBP) and received therapy for
>=4 wk after first progression; patients not treated beyond RECIST progression
(NTBP) received 0 wk to <4 wk of therapy after progression. INTERVENTIONS:
Nivolumab 3mg/kg intravenously every 2 wk. RESULTS AND LIMITATIONS: Of 406
nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who
progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response
rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patients TBP and
NTBP, respectively. Differences in clinical characteristics assessed at first
progression between patients TBP versus NTBP included better Karnofsky
performance status, less deterioration in Karnofsky performance status, shorter
time to response, lower incidence of new bone lesions, and improved quality of
life. Postprogression, 13% of all patients TBP (20/153) had >=30% tumor burden
reduction including patients with preprogression and postprogression tumor
measurements (n=142) and complete/partial response (28%, 8/29), stable disease
(6%, 3/47), and progressive disease (14%, 9/66) as their best response before
being TBP. Incidence of treatment-related adverse events in patients TBP was
lower after (59%) versus before (71%) progression. Limitations included potential
bias from the nonrandomized nature of the analysis. CONCLUSIONS: A subset of
patients with advanced renal cell carcinoma and RECIST progression experienced
tumor reduction postprogression with nivolumab, and had an acceptable safety
profile. Clinical judgment remains essential when switching therapy.
ClinicalTrials.gov Identifier: NCT01668784. PATIENT SUMMARY: A subset of patients
with advanced renal cell carcinoma and disease progression may continue to
benefit from nivolumab treatment beyond progression as evidenced by tumor
reduction postprogression and an acceptable safety profile.
PMID- 28410867
TI - Psychotropic implant can be a new hope in psychiatry.
AB - Non-adherence to oral psychotropic medications is common in patients with severe
mental illness (SMI). This substantially limits the effectiveness of treatment
and results in higher rates of relapse, rehospitalization, suicide, early
mortality and disability in SMI. This is a major concern for professionals,
caregivers and policy makers. The pharmacological, psychological, psychosocial
models and interventions have been there since last few decades to address non
adherence. These have not made major changes in treatment adherence and outcome
of SMI. Hence new powerful, long acting and novel psychotropic implant can be
developed and could soon revolutionize the treatment in psychiatry.
PMID- 28410868
TI - Quantifying cardiorespiratory responses resulting from speed and slope increments
during motorized treadmill propulsion among manual wheelchair users.
AB - BACKGROUND: Cardiorespiratory fitness assessment and training among manual
wheelchair (MW) users are predominantly done with an arm-crank ergometer.
However, arm-crank ergometer biomechanics differ substantially from MW propulsion
biomechanics. This study aimed to quantify cardiorespiratory responses resulting
from speed and slope increments during MW propulsion on a motorized treadmill and
to calculate a predictive equation based on speed and slope for estimating peak
oxygen uptake (VO2peak) in MW users. METHODS: In total, 17 long-term MW users
completed 12 MW propulsion periods (PP), each lasting 2min, on a motorized
treadmill, in a random order. Each PP was separated by a 2-min rest. PPs were
characterized by a combination of 3 speeds (0.6, 0.8 and 1.0m/s) and 4 slopes (0
degrees , 2.7 degrees , 3.6 degrees and 4.8 degrees ). Six key cardiorespiratory
outcome measures (VO2, heart rate, respiratory rate, minute ventilation and tidal
volume) were recorded by using a gas-exchange analysis system. Rate of perceived
exertion (RPE) was measured by using the modified 10-point Borg scale after each
PP. RESULTS: For the 14 participants who completed the test, cardiorespiratory
responses increased in response to speed and/or slope increments, except those
recorded between the 3.6o and 4.8o slope, for which most outcome measures were
comparable. The RPE was positively associated with cardiorespiratory response
(rs>=0.85). A VO2 predictive equation (R2=99.7%) based on speed and slope for
each PP was computed. This equation informed the development of a future testing
protocol to linearly increase VO2 via 1-min stages during treadmill MW
propulsion. CONCLUSIONS: Increasing speed and slope while propelling a MW on a
motorized treadmill increases cardiorespiratory response along with RPE. RPE can
be used to easily and accurately monitor cardiorespiratory responses during MW
exercise. The VO2 can be predicted to some extent by speed and slope during MW
propulsion. A testing protocol is proposed to assess cardiorespiratory fitness
during motorized MW propulsion.
PMID- 28410869
TI - Effect of natural and semi-synthetic cadinanes from Heterotheca inuloides on NF
kappaB, Nrf2 and STAT3 signaling pathways and evaluation of their in vitro
cytotoxicity in human cancer cell lines.
AB - The effects of ten natural cadinane sesquiterpenoids isolated from Heterotheca
inuloides on the pathways of the NF-kappaB, Nrf2 and STAT3 transcription factors
were studied for the first time. The main constituent in this species, 7-hydroxy
3,4-dihydrocadalene (1), showed anti-NF-kappaB activity and activated the
antioxidant Nrf2 pathway, which may explain the properties reported for the
traditional use of the plant. In addition to the main metabolite, a structurally
similar compound, 7-hydroxy-cadalene (2), also displayed anti-NF-kappaB activity.
Thus, both natural compounds were used as templates for the preparation of a
novel semi-synthetic derivative set, including esters and carbamates, which were
evaluated for their potential in vitro antiproliferative activities against six
human cancer cell lines. Carbamate derivatives 32 and 33 were found to exhibit
potent activity against human colorectal adenocarcinoma and showed important
selectivity in cancer cells. Among ester derivatives, compound 13 was determined
to be a more potent NF-kappaB inhibitor and Nrf2 activator than its parent, 7
hydroxy-3,4-dihydrocadalene (1). Furthermore, this compound decreases levels of
phospho-IkappaBalpha, a protein complex involved in the NF-kappaB activation
pathway. Molecular simulations suggest that all active compounds interact with
the activation loop of the IKKbeta subunit in the IKK complex, which is the
responsible of IkappaBalpha phosphorylation. Thus, we identified two natural, and
one semi-synthetic, NF-kappaB and Nrf2 modulators and two new promising cytotoxic
compounds.
PMID- 28410870
TI - Interleukin-33 in children with asthma: A systematic review and meta-analysis.
AB - BACKGROUND: Previous studies have shown that serum interleukin 33 serving as an
"alarmin" is increased in children with asthma. The objective of this study was
to assess the validity of serum IL33 test for early diagnosis of childhood
asthma. METHODS: A literature search was performed in June 2016 using PubMed,
Embase, the Cochrane Library and other Chinese Medical Databases to identify
studies. The search terms used were "cytokine", "interleukin-33", "asthma" and
"children". The meta-analysis was performed using Review Manager 5.3 software.
Random-effects model was used to estimate the standardized mean differences
(SMDs) with 95% confidence intervals (CIs). RESULTS: A total of eight studies
were included into this meta-analysis, involving 330 asthmatic children and 248
healthy children. The meta-analysis results revealed that the serum IL33 level
was higher in asthmatic children compared to that in healthy children (SMD=1.29,
95%CI=0.53-2.05, P=0.0009), with significant heterogeneity across studies (I2=94%
and P<0.00001). CONCLUSIONS: The meta-analysis showed that serum IL33 is a
helpful biomarker for early diagnosis of childhood asthma. However, owing to lack
of enough data, the increased serum concentration of IL33 cannot be an indicator
for the asthma severity.
PMID- 28410871
TI - Is the evidence of breast feeding protection against coeliac disease real?
AB - Many recent studies discredit breastfeeding protection against coeliac disease.
We will try to answer the question: "Is the evidence of breast feeding protection
against coeliac disease real?"
PMID- 28410872
TI - Prevalence and risk factors for wheezing and allergic diseases in preschool
children: A perspective from the Mediterranean coast of Turkey.
AB - OBJECTIVES: The aim of the present study was to determine the prevalence and risk
factors of allergic diseases in preschool children from one of the biggest cities
in the Mediterranean Region of Turkey. METHODS: The study population included 396
preschool children attending to urban daycare centres in Mersin. In the first
stage, a comprehensive standardised questionnaire modified from the International
Study of Asthma and Allergies in Childhood (ISAAC) was employed. In the second
stage, serum food and inhalant specific IgE, and skin tests were performed in 45
children with frequent wheezing and 28 children with no wheezing. RESULTS: The
prevalence of ever wheezing, current wheezing, physician-diagnosed asthma,
allergic rhinitis and eczema were 53% (210), 33.3% (132), 27.3% (108), 13.4% (53)
and 8.3% (33), respectively. A family history of atopy (OR=2.5, 95% CI: 1.3-4.7,
p=0.004), dampness at home (OR=2.4, 95% CI: 1.2-4.8, p=0.008), a history of
intestinal parasites (OR=4.3, 95% CI: 1.7-10.9, p=0.002), previous history of
pneumonia (OR=6.9, 95% CI: 1.9-25.9, p=0.004), initiation of complementary foods
before the age of three months (OR=6.1, 95%CI: 1.4-26.9, p=0.02) and presence of
food allergy (OR=3.1, 95% CI: 1.1-9.2, p=0.03) were found to be significant risk
factors for physician-diagnosed asthma. The risk factors for frequent wheezing
were maternal smoking during pregnancy (OR=5.2, 95% CI: 0.9-28.7, p=0.05) and
high serum IgE levels (OR=2.9, 95% CI: 0.9-9.0, p=0.05) at borderline
significance. CONCLUSION: Our study was the first epidemiological study in
preschool children in the Mediterranean region of Turkey and demonstrated a high
prevalence of asthma and allergic diseases, probably related to humid climatic
properties in addition to other environmental and genetic factors.
PMID- 28410873
TI - Under the superficial dichotomy pathogen and allergen are two manifestations of
same immune activation and pathogenesis mechanisms.
AB - Pathogens and allergens are deemed as two contrasting facets of host immune
status, deficiency and exuberant. In silico domain analysis of a diverse panel of
pathogen and allergen proteins has revealed the shortcoming of this notion. Both
the pathogen and allergen proteins elicit immune activation, with the outcome of
immune agitation depending on the pathogen strain, allergen exposure duration,
and host factors. Pathogens can replicate within the host and constantly irritate
the immune system, leading to blood coagulation, respiratory collapse and death.
Allergens, being non-viable, can only provoke the immune system transiently;
however, depending on the allergen dose and extent exposed to, inflammation and
fatality can occur. In silico analysis of pathogen and allergen proteins showed
the conserved domains to be AAA, WR1, VKc, Kelch, Hr1, HAMP, HELICc, Dak2, CHAD,
CHASE2, Galanin, PKS_TE, Robl_LC7, Excalibur, DISIN, etc. This exciting discovery
can have far-reaching effects in drug target identification approaches.
PMID- 28410874
TI - Predictivity of clinical efficacy of sublingual immunotherapy (SLIT) based on
sensitisation pattern to molecular allergens in children with allergic
rhinoconjunctivitis.
AB - BACKGROUND: The diagnostic and therapeutic approach to grass pollen allergy is
now possible by detecting specific IgE (sIgE) to its allergenic components. AIM:
To evaluate the correlation between the sensitisation to different molecular
Phleum pratense (Phl p) allergens and clinical efficacy of SLIT. METHODS: The
pilot study included 36 patients affected by allergic rhinoconjunctivitis, all
treated with SLIT actively. We performed serum analysis of sIgE to Phl p 1, 2, 4,
5, 6, 7, 11 and 12. The Average Rhinoconjunctivitis Total Symptom Score (ARTSS)
and the Average Combined Score (ACS) were evaluated before and after one year of
immunotherapy. RESULTS: Three different groups of sensitisation were defined
based on the range of IgE reactivity to Phleum pratense allergens at baseline:
group I (sIgE reactive to 1-3 allergens); group II (sIgE reactive to 4-5
allergens); and group III (sIgE reactive to 6-8 allergens). At T0 ACS was 1.79+/
0.18 in group I; 1.81+/-0.23 in group II; and 1.95+/-0.34 in group III. At T1 ACS
was 0.85+/-0.55 in group I; 1.01+/-0.31 in group II; and 1.44+/-0.39 in group
III. At T1 there was a significant improvement of ARTSS and ACS for group I
(p=0.001). CONCLUSIONS: Sublingual immunotherapy with a grass pollen is
efficacious irrespective of the patients' baseline sensitisation to either single
or multiple grass pollen molecular allergens. We found that patients with few
sensitisations have a greater improvement in combined symptom and medication
score. SLIT improves the clinical course of allergic patients although new
sensitisations may appear.
PMID- 28410875
TI - Particle sorting by Paramecium cilia arrays.
AB - Motile cilia are cell-surface organelles whose purposes, in ciliated protists and
certain ciliated metazoan epithelia, include generating fluid flow, sensing and
substance uptake. Certain properties of cilia arrays, such as beating
synchronisation and manipulation of external proximate particulate matter, are
considered emergent, but remain incompletely characterised despite these
phenomena having being the subject of extensive modelling. This study constitutes
a laboratory experimental characterisation of one of the emergent properties of
motile cilia: manipulation of adjacent particulates. The work demonstrates
through automated videomicrographic particle tracking that interactions between
microparticles and somatic cilia arrays of the ciliated model organism Paramecium
caudatum constitute a form of rudimentary 'sorting'. Small particles are drawn
into the organism's proximity by cilia-induced fluid currents at all times,
whereas larger particles may be held immobile at a distance from the cell margin
when the cell generates characteristic feeding currents in the surrounding media.
These findings can contribute to the design and fabrication of biomimetic cilia,
with potential applications to the study of ciliopathies.
PMID- 28410876
TI - The treatment of fatigue by non-invasive brain stimulation.
AB - The use of non-invasive brain neurostimulation (NIBS) techniques to treat
neurological or psychiatric diseases is currently under development. Fatigue is a
commonly observed symptom in the field of potentially treatable pathologies by
NIBS, yet very little data has been published regarding its treatment. We
conducted a review of the literature until the end of February 2017 to analyze
all the studies that reported a clinical assessment of the effects of NIBS
techniques on fatigue. We have limited our analysis to repetitive transcranial
magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS).
We found only 15 studies on this subject, including 8 tDCS studies and 7 rTMS
studies. Of the tDCS studies, 6 concerned patients with multiple sclerosis while
6 rTMS studies concerned fibromyalgia or chronic fatigue syndrome. The remaining
3 studies included patients with post-polio syndrome, Parkinson's disease and
amyotrophic lateral sclerosis. Three cortical regions were targeted: the primary
sensorimotor cortex, the dorsolateral prefrontal cortex and the posterior
parietal cortex. In all cases, tDCS protocols were performed according to a
bipolar montage with the anode over the cortical target. On the other hand, rTMS
protocols consisted of either high-frequency phasic stimulation or low-frequency
tonic stimulation. The results available to date are still too few, partial and
heterogeneous as to the methods applied, the clinical profile of the patients and
the variables studied (different fatigue scores) in order to draw any conclusion.
However, the effects obtained, especially in multiple sclerosis and fibromyalgia,
are really carriers of therapeutic hope.
PMID- 28410877
TI - Chronic fatigue syndrome and the immune system: Where are we now?
AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterised by
multiple symptoms including fatigue, headaches and cognitive impairment, which
have a significantly adverse effect on the normal functioning and well-being of
the individual. These symptoms are often triggered or worsened following physical
or mental exertion. ME/CFS has long been thought of as having a significant
immunological component, but reports describing changes in immune function are
often inconsistent between study groups. Although the wide range of physical,
neurocognitive and autonomic symptoms reported have seriously hampered attempts
to understand pathophysiological pathways, investment in biomedical research in
ME/CFS is finally increasing with a number of novel and promising investigations
being published. The onset of ME/CFS may often be linked to (viral) infections
which would be consistent with a variety of alterations in natural killer (NK)
cell function as described by a number of different groups. Consistency in
cytokine data has been lacking so far, although recently more sophisticated
approaches have led to more robust data from large patient cohorts. New hope has
also been given to sufferers with the possibility that therapies that deplete B
cells can result in clinical improvement. To understand the pathogenic mechanism
in this complex condition, it is important to consider repeated analysis in
different cohorts. In this review, we will discuss the potential of different
components of the immune system to be involved in the pathogenesis of ME/CFS.
PMID- 28410878
TI - Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who
initiated enzyme replacement therapy in adult age. A systematic review and meta
analysis.
AB - BACKGROUND: The efficacy of starting enzyme replacement therapy (ERT) in adults
with Muchopolysaccharidosis Type I (MPS-I) is controversial. Evaluating the
benefits reported by patients initiating ERT with laronidase at adult age might
help physicians decide whether the use of ERT in these patients is worthwhile
from a clinical point of view. OBJECTIVE: To assess every effectiveness variable
modified in MPS-I patients who initiated laronidase at adult age. METHODS: A
systematic search of the literature, from inception to July 2016, was conducted
using MEDLINE, EMBASE, CENTRAL and LILACS to identify randomized trials or
observational studies including >=1 MPS-I patients with ERT initiated in adult
age (>=18years) and evaluating ERT efficacy. A meta-analysis of studies
evaluating the same effectiveness outcome was performed and the evidence was
rated according to GRADE criteria. Heterogeneity was assessed by the Chi-squared
test and the I-squared statistic. Case reports were excluded from meta-analysis
but their main outcomes were separately evaluated. The decrease in urine
glycosaminoglycans (uGAGs) levels as patient percentage with reduction in uGAGs
and with normalization was the primary outcome. RESULTS: Nineteen clinical
studies and 12 case reports were selected. ERT decreased uGAG levels (high
evidence) and liver volume (high), improved 6-min walking test (6MWT) (moderate)
and increased blood anti-ERT antibody levels (high). There was no conclusive
results (low or very low evidence) regarding improvement/stabilization of
respiratory function, change in shoulder flexion, cardiac
improvement/stabilization, improvement in symptoms of nocturnal hypoventilation
and sleep apnea, improvement in quality of life, visual acuity, otolaryngologic
function, bone mineral density or effectiveness of intrathecal therapy.
LIMITATIONS: Excluding case reports, there was no study conducted specifically in
the target population (ERT >=18years). Data were from subgroup analyses of
selected studies. There was a great heterogeneity between designs and clinical
outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver volume in MPS-I
patients initiating therapy as adults, although the putative clinical benefit
associated to these improvements is unclear. Moderate evidence was shown for
improvement in 6MWT. Systematic review registration number (PROSPERO):
42,016,041,306.
PMID- 28410879
TI - Determination of reference genes that are independent of feeding rhythms for
circadian studies of mouse metabolic tissues.
AB - Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis is a
popular method for the measurement of mRNA expression level and is a critical
tool for basic research. The identification of suitable reference genes that are
stable and not affected by experimental conditions is a critical step in the
accurate normalization of RT-PCR. On the other hand, the levels of numerous
transcripts exhibit circadian oscillation in various peripheral tissues and it is
thought to be regulated by feeding rhythms in addition to the molecular circadian
clock. Here, we investigated the effects of feeding schedule on the temporal
expression profiles of 13 common housekeeping genes in metabolic tissues of mice
fed during either the sleep or the active phase. The expression of most of these
genes fluctuated dependently on feeding rhythms in the liver and WAT, but not in
skeletal muscle. Two-way analyses of variance (ANOVA) identified 18S ribosomal
RNA (Rn18s) as the only gene that was stably expressed throughout the day
independently of feeding schedules in the liver and WAT, although RefFinder
software showed that peptidylprolyl isomerase A (Ppia) was the most stably
expressed housekeeping gene. Both ANOVA and RefFinder software determined that
Actb was the preferred reference gene for skeletal muscle. Furthermore,
NormFinder proposed that the optimal pairs of reference genes were beta-2
microglobulin (B2m)-Ppia in the liver, Ppia-TATA box binding protein (Tbp) in
WAT, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,
zeta polypeptide (Ywhaz)-glyceraldehyde-3-phosphate dehydrogenase (Gapdh) in
skeletal muscle, and that their stability value was better than that of a single
stable gene. The appropriate reference gene pairs for normalizing genes of
interest in mouse circadian studies are B2m-Ppia in the liver, Ppia-Tbp in WAT,
and Ywhaz-Gapdh in skeletal muscle.
PMID- 28410880
TI - The effect of user experience and inflation technique on endotracheal tube cuff
pressure using a feline airway simulator.
AB - OBJECTIVE: The effect of user experience and inflation technique on endotracheal
tube cuff pressure using a feline airway simulator. STUDY DESIGN: Prospective,
experimental clinical study. METHODS: Participants included veterinary students
at the beginning (group S1) and end (group S2) of their 2-week anaesthesia
rotation and veterinary anaesthetists (group A). The feline airway simulator was
designed to simulate an average size feline trachea, intubated with a 4.5 mm low
pressure, high-volume cuffed endotracheal tube, connected to a Bain breathing
system with oxygen flow of 2 L minute-1. Participants inflated the on
endotracheal tube cuff by pilot balloon palpation and by instilling the minimum
occlusive volume (MOV) required for loss of airway leaks during manual
ventilation. Intracuff pressures were measured by manometers obscured to
participants and ideally were 20-30 cm H2O. Student t, Fisher exact, and Chi
squared tests were used where appropriate to analyse data (p < 0.05). RESULTS:
Participants were 12 students and eight anaesthetists. Measured intracuff
pressures for palpation and MOV, respectively, were 19 +/- 12 and 29 +/- 19 cm
H2O for group S1, 10 +/- 5 and 20 +/- 11 cm H2O for group S2 and 13 +/- 6 and 29
+/- 18 cm H2O for group A. All groups performed poorly at achieving intracuff
pressures within the ideal range. There was no significant difference in
intracuff pressures between techniques. Students administered lower (p = 0.02)
intracuff pressures using palpation after their training. CONCLUSIONS AND
CLINICAL RELEVANCE: When using palpation and MOV for cuff inflation operators
rarely achieved optimal intracuff pressures. Experience had no effect on this
skill and, as such, a cuff manometer is recommended.
PMID- 28410881
TI - Patterns, Policy and Appropriateness: A 12-Year Utilization Review of Blood
Glucose Test Strip Use in Insulin Users.
AB - OBJECTIVES: Considerable attention has been paid to the rising costs of the use
of blood glucose test strips (BGTS). Insulin users have generally been treated as
a single homogeneous group, resulting in policies that cap usage (8.2 strips/day)
in provincial drug insurance programs. The objective of this study was to conduct
a utilization review of BGTS by insulin users and to evaluate use patterns
against current insulin use patterns and BGTS policy. METHODS: BGTS usage was
examined in a cohort of insulin users with type 1 and type 2 diabetes over a 12
year period (2001 to 2013) using the population-based administrative data in
Manitoba, Canada. RESULTS: Total BGTS strip use increased by 121%, from $4.3 to
$9.5 million. However, the number of insulin users also increased by 115%. Use
has been stable at 1.5 strips per day per person since 2004 by insulin users with
type 2 diabetes but has risen from 1.9 to 3.0 strips per day per person in those
with type 1 diabetes. Mean daily test strip use was below the number of daily
tests recommended for patients using insulin as per the current Canadian
guidelines, with 11% and 15% of insulin users with type 1 and type 2 diabetes not
claiming any BGTS use and a further 15% (type 1) and 28% (type 2) using fewer
than 1 strip per day. CONCLUSIONS: BGTS use per insulin user has been stable for
most of the past decade, and the vast majority of use falls well below provincial
insurance caps. The amount of low-level testing (0 to <1 strip/day) suggests that
greater attention should be directed to ensuring a safe level of testing by all
insulin users.
PMID- 28410883
TI - Aminoglutethimide-induced lysosomal changes in adrenal gland in mice.
AB - Aminoglutethimide is a steroidogenesis inhibitor and inhibits a cholesterol side
chain cleavage enzyme (CYP11A1) that converts cholesterol to pregnenolone in
mitochondria. We investigated histopathological changes induced by 5-day
administration of AG in mice. Cytoplasmic vacuoles of various sizes and single
cell necrosis were found in zona fasciculata cells in AG-treated mice. Some
vacuoles were positive for adipophilin, whereas others were positive for lysosome
associated membrane protein-2 on immunohistochemical staining, indicating they
were enlarged lipid droplets and lysosomes, respectively. Electron microscopy
revealed enlarged lysosomes containing damaged mitochondria and lamellar bodies
in zona fasciculata cells, and they were considered to reflect the intracellular
protein degradation processes, mitophagy and lipophagy. From these results, we
showed that AG induces excessive lipid accumulation and mitochondrial damage in
zona fasciculata cells, which leads to an accelerated lysosomal degradation in
mice.
PMID- 28410884
TI - The effect of transcranial direct current stimulation on motor sequence learning
and upper limb function after stroke.
AB - OBJECTIVE: To assess the impact of electrode arrangement on the efficacy of tDCS
in stroke survivors and determine whether changes in transcallosal inhibition
(TCI) underlie improvements. METHODS: 24 stroke survivors (3-124months post
stroke) with upper limb impairment participated. They received blinded tDCS
during a motor sequence learning task, requiring the paretic arm to direct a
cursor to illuminating targets on a monitor. Four tDCS conditions were studied
(crossover); anodal to ipsilesional M1, cathodal to contralesional M1,
bihemispheric, sham. The Jebsen Taylor hand function test (JTT) was assessed pre-
and post-stimulation and TCI assessed as the ipsilateral silent period (iSP)
duration using transcranial magnetic stimulation. RESULTS: The time to react to
target illumination reduced with learning of the movement sequence, irrespective
of tDCS condition (p>0.1). JTT performance improved after unilateral tDCS (anodal
or cathodal) compared with sham (p<0.05), but not after bihemispheric (p>0.1).
There was no effect of tDCS on change in iSP duration (p>0.1). CONCLUSIONS:
Unilateral tDCS is effective for improving JTT performance, but not motor
sequence learning. SIGNIFICANCE: This has implications for the design of future
clinical trials.
PMID- 28410885
TI - Successful implantation and immediate activation of Vagus Nerve Stimulation (VNS)
during pregnancy in a patient with intractable epilepsy: A case illustration and
review of the literature.
AB - While Vagus Nerve Stimulation (VNS) is proven to be a safe and effective
adjunctive therapy in the general population with medically intractable seizures,
little is published about its implantation during pregnancy. Here we illustrate
the case of a 21year old primigravid woman with medically refractory seizures who
underwent safe and successful VNS implantation and immediate activation of the
device in her 32nd week of pregnancy, resulting in dramatically improved seizure
control and subsequent delivery of a healthy baby.
PMID- 28410882
TI - Epo reprograms the epigenome of erythroid cells.
AB - The hormone erythropoietin (Epo) is required for erythropoiesis, yet its
molecular mechanism of action remains poorly understood, particularly with
respect to chromatin dynamics. To investigate how Epo modulates the erythroid
epigenome, we performed epigenetic profiling using an ex vivo murine cell system
that undergoes synchronous erythroid maturation in response to Epo stimulation.
Our findings define the repertoire of Epo-modulated enhancers, illuminating a new
facet of Epo signaling. First, a large number of enhancers rapidly responded to
Epo stimulation, revealing a cis-regulatory network of Epo-responsive enhancers.
In contrast, most of the other identified enhancers remained in an active
acetylated state during Epo signaling, suggesting that most erythroid enhancers
are established at an earlier precursor stage. Second, we identified several
hundred super-enhancers that were linked to key erythroid genes, such as Tal1,
Bcl11a, and Mir144/451. Third, experimental and computational validation revealed
that many predicted enhancer regions were occupied by TAL1 and enriched with DNA
binding motifs for GATA1, KLF1, TAL1/E-box, and STAT5. Additionally, many of
these cis-regulatory regions were conserved evolutionarily and displayed
correlated enhancer:promoter acetylation. Together, these findings define a cis
regulatory enhancer network for Epo signaling during erythropoiesis, and provide
the framework for future studies involving the interplay of epigenetics and Epo
signaling.
PMID- 28410886
TI - The autogenous graft versus transport distraction osteogenesis for reconstruction
of the ramus-condyle unit: a prospective comparative study.
AB - This study aimed to compare the joint function and morphology achieved following
condylar reconstruction using sternoclavicular grafts (SCG) versus transport
distraction osteogenesis (TDO) in temporomandibular joint (TMJ) ankylosis
patients. Twenty-two patients with TMJ ankylosis underwent TMJ reconstruction
with SCG or TDO (n=11 each). Radiographic and clinical evaluations were performed
at 1 week and at 1, 3, and 6 months post-surgery. Clinical criteria examined
included the duration of surgery, mean postoperative mouth opening, excursive jaw
movements, and pain scores. The radiographic evaluation 6 months postoperatively
(computed tomography) included subjective assessment of joint morphology and
measurements of the mean condylar height, width achieved, and amount of condylar
resorption. The chi2 test and Student t-test were used to compare qualitative and
quantitative variables, respectively. Similar mean mouth opening (SCG=31.8mm,
TDO=32.1mm at 6 months), excursive movements, and pain scores were observed in
the two groups throughout follow-up. Mean condylar resorption was significantly
greater in the TDO group (TDO=7.0mm, SCG=2.7mm; P=0.005). The duration of
reconstruction surgery was greater in the SCG group (P=0.035). A greater
incidence of complications was observed with TDO. In conclusion, based on the
protocols used in this study, SCGs are superior to TDO in terms of condylar
morphology, stability, and surgical safety.
PMID- 28410887
TI - On "Cleft relapse and oronasal fistula after Furlow palatoplasty in infants with
cleft palate: incidence and risk factors" by Li et al.
PMID- 28410888
TI - Temperature control strategy to enhance the activity of yeast inoculated into
compost raw material for accelerated composting.
AB - The effects of inoculating the mesophilic yeast Pichia kudriavzevii RB1, which is
able to degrade organic acids, on organic matter degradation in composting were
elucidated. When model food waste with high carbohydrate content (C/N=22.3) was
used, fluctuation in the inoculated yeast cell density was observed, as well as
fluctuation in the composting temperature until day 5 when the temperature rose
to 60 degrees C, which is lethal for the yeast. After the decrease in yeast,
acetic acid accumulated to levels as high as 20mg/g-ds in the composting material
and vigorous organic matter degradation was inhibited. However, by maintaining
the temperature at 40 degrees C for 2days during the heating phase in the early
stage of composting, both the organic acids originally contained in the raw
material and acetic acid produced during the heating phase were degraded by the
yeast. The concentration of acetic acid was kept at a relatively low level
(10.1mg/g-ds at the highest), thereby promoting the degradation of organic matter
by other microorganisms and accelerating the composting process. These results
indicate that temperature control enhances the effects of microbial inoculation
into composts.
PMID- 28410889
TI - Methodology for the determination of optimum power of a Thermal Power Plant (TPP)
by biogas from sanitary landfill.
AB - This study aimed to determine theoretically, the electrical optimum power of LFG
using the maximum net benefit (MNB) methodology, and taking into consideration
the economic, demographic, and regional aspects of the Inter municipal Consortium
of the Micro-region of the High Sapucai for Sanitary Landfill (CIMASAS, as
acronym in Portuguese), that is located in the southern part of the State of
Minas Gerais, Brazil. To this end, the prognosis for a 20-year period of
household solid waste generation in this region was estimated and quantified
based on population data, in order to estimate the LFG production and the energy
that can be generated. From this point, the optimum power for thermal power plant
(TPP) by LFG was determined. The results indicated that the landfill in this
region could produce more 66,293,282m3CH4 (with maximum power of 997kW in 2036)
in twenty years and that there would be no economic viability to generate energy
from LFG, because the Net Present Value (NPV) would not be positive. The smallest
population to that can achieve a minimum attractiveness rate (MAR) of 15% should
be 3,700,000 inhabitants under the conditions studied. Considering the Brazilian
National Electric Energy Agency (ANEEL) Resolutions, it would be 339,000
inhabitants with an installed power of 440kW. In addition, the outcome of the
CIMASAS case-study demonstrated the applicability of MNB methodology for the
determination of TPP optimum power.
PMID- 28410890
TI - Pyrolysis of automotive shredder residue in a bench scale rotary kiln.
AB - Automotive shredder residue (ASR) can create difficulties when managing, with its
production increasing. It is made of different type of plastics, foams,
elastomers, wood, glasses and textiles. For this reason, it is complicated to
dispose of in a cost effective way, while also respecting the stringent
environmental restrictions. Among thermal treatments, pyrolysis seems to offer an
environmentally attractive method for the treatment of ASR; it also allows for
the recovery of valuable secondary materials/fuels such as pyrolysis oils, chars,
and gas. While, there is a great deal of significant research on ASR pyrolysis,
the literature on higher scale pyrolysis experiments is limited. To improve
current literature, the aim of the study was to investigate the pyrolysis of ASR
in a bench scale rotary kiln. The Italian ASR was separated by dry-sieving into
two particle size fractions: d<30mm and d>30mm. Both the streams were grounded,
pelletized and then pyrolyzed in a continuous bench scale rotary kiln at 450, 550
and 650 degrees C. The mass flow rate of the ASR pellets was 200-350g/h and each
test ran for about 4-5h. The produced char, pyrolysis oil and syngas were
quantified to determine product distribution. They were thoroughly analyzed with
regard to their chemical and physical properties. The results show how higher
temperatures increase the pyrolysis gas yield (44wt% at 650 degrees C) as well as
its heating value. The low heating value (LHV) of syngas ranges between 18 and
26MJ/Nm3dry. The highest pyrolysis oil yield (33wt.%) was observed at 550 degrees
C and its LHV ranges between 12.5 and 14.5MJ/kg. Furthermore, only two out of the
six produced chars respect the LHV limit set by the Italian environmental
regulations for landfilling. The obtained results in terms of product
distribution and their chemical-physical analyses provide useful information for
plant scale-up.
PMID- 28410891
TI - Advancing our Understanding of Ubiquitination Using the Ub-Toolkit.
AB - Post-translational protein modification by ubiquitin (Ub) and Ub-like modifiers
is orchestrated by the sequential action of Ub-activating, -conjugating, and
ligating enzymes to regulate a vast array of fundamental biological processes.
Unsurprisingly, the dysregulation of the intricate interplay between
ubiquitination and deubiquitination gives rise to numerous pathologies, most
notably cancer and neurodegenerative diseases. While activity-based probes (ABPs)
and assay reagents have been extensively developed and applied for
deubiquitinating enzymes, similar tools for the Ub cascade have only recently
emerged. Given the recent efforts to develop inhibitors for the Ub system, the
urgency for developing ABPs and assay reagents is imminent. In this light, we
comprehensively discuss the currently available ABPs with a focus on the newly
developed reagents targeting the Ub cascade while illustrating their potential
applications.
PMID- 28410892
TI - Antiplatelet therapy suspension in patients undergoing coronary surgery for acute
coronary syndrome: Is point-of-care guided strategy the best choice?
PMID- 28410893
TI - Need for Caution in Diagnosis of Irritable Bowel Syndrome in Patients With
Inflammatory Bowel Disease.
PMID- 28410894
TI - Analysis of Functional Luminal Imaging Probe Data.
PMID- 28410895
TI - Unusual Submucosal Tumor in the Rectosigmoid Colon.
PMID- 28410896
TI - White Paper AGA: Gastroparesis: Clinical and Regulatory Insights for Clinical
Trials.
AB - Gastroparesis continues to represent a large unmet clinical need and a major
opportunity for new drug development. This has led to increasing interest by
federal funding agencies, regulatory bodies, and industry. This article
summarizes the proceedings of the gastroparesis section of the "Drug Development
Conference: Clinical Endpoints in Upper GI Disorders" organized by the American
Gastroenterological Association in Washington, DC, on October 27-28, 2016. The
presentation, diagnosis, and current therapeutic strategies are briefly reviewed,
followed by a detailed discussion of the regulatory strategy, recommended
endpoints, and future directions.
PMID- 28410897
TI - Efficient production of antibody Fab fragment by transient gene expression in
insect cells.
AB - Transient gene expression allows a rapid production of diverse recombinant
proteins in early-stage preclinical and clinical developments of biologics.
Insect cells have proven to be an excellent platform for the production of
functional recombinant proteins. In the present study, the production of an
antibody Fab fragment by transient gene expression in lepidopteran insect cells
was investigated. The DNA fragments encoding heavy-chain (Hc; Fd fragment) and
light-chain (Lc) genes of an Fab fragment were individually cloned into the
plasmid vector pIHAneo, which contained the Bombyx mori actin promoter downstream
of the B. mori nucleopolyhedrovirus (BmNPV) IE-1 transactivator and the BmNPV HR3
enhancer for high-level expression. Trichoplusia ni BTI-TN-5B1-4 (High Five)
cells were co-transfected with the resultant plasmid vectors using linear
polyethyleneimine. When the transfection efficiency was evaluated, a plasmid
vector encoding an enhanced green fluorescent protein (EGFP) gene was also co
transfected. Transfection and culture conditions were optimized based on both the
flow cytometry of the EGFP expression in transfected cells and the yield of the
secreted Fab fragments determined by enzyme-linked immunosorbent assay (ELISA).
Under optimal conditions, a yield of approximately 120 mg/L of Fab fragments was
achieved in 5 days in a shake-flask culture. Transient gene expression in insect
cells may offer a promising approach to the high-throughput production of
recombinant proteins.
PMID- 28410899
TI - ?
PMID- 28410900
TI - ?
PMID- 28410898
TI - Inactivation kinetics and conformation change of Hypocrea orientalis beta
glucosidase with guanidine hydrochloride.
AB - The relationship between unfolding and inactivation of Hypocrea orientalis beta
glucosidase has been investigated for the first time. The secretion of beta
glucosidase from H. orientalis is induced by raw cassava residues. The enzyme was
75 kD without glycosylation. Guanidine hydrochloride (GuHCl) could reversibly
inactivate the enzyme with an estimated IC50 value of 0.4 M. The inactivation
kinetics model by GuHCl has been established and the microscopic inactivation
rate constants are determined. The values of forward inactivation rate constants
of free enzyme are found to be larger than that of substrate-enzyme complex
suggesting the enzyme could be protected by substrate during denaturation.
Conformational change of the enzyme during denaturation is observed as the
intrinsic fluorescence emission peaks appeared red-shift (334-354 nm) with
intensity decreased following increase of GuHCl concentrations. Inactivation
extent is found to be greater than conformation change of the whole enzyme,
indicating that the active site of H. orientalis beta-glucosidase might be a more
flexible region than the whole enzyme.
PMID- 28410901
TI - Unicornuate Uterus in Klippel-Feil Syndrome.
PMID- 28410902
TI - Use of Narrowband Imaging for the Surgical Management of Endometriosis.
PMID- 28410903
TI - ?
PMID- 28410904
TI - ?
PMID- 28410906
TI - Angular Pregnancy, Interstitial Pregnancy, Caesarean Scar Pregnancy and Multidose
Methotrexate.
PMID- 28410905
TI - Correction.
PMID- 28410907
TI - ?
PMID- 28410908
TI - National Utilization of Partial Nephrectomy Pre- and Post- AUA Guidelines: Is
This as Good as It Gets?
AB - BACKGROUND: The purpose of the study was to compare utilization and predictors of
partial nephrectomy (PN) in the pre- and post-guideline eras. MATERIALS AND
METHODS: American Board of Urology certification/recertification operative logs
were reviewed from 2003 to 2014. Nephrectomy cases were extracted using Current
Procedural Terminology codes. The cases were then stratified according to pre
guidelines (2003-October 2009) and post-guidelines (November 2009-2014).
Multivariable logistic regression was used to evaluate patient, surgeon, and
practice characteristics as predictors of PN. A general linear model with
regression analysis was used to evaluate the change in PN over time relative to
the incidence of renal cell carcinoma (RCC). RESULTS: We identified 20,402 and
20,729 nephrectomies in the pre- and post-guidelines eras, respectively. In
multivariable analysis, the post-guidelines group was more likely to undergo PN
(odds ratio, 1.87; P < .001). The pre- as well as post-guidelines groups had a
higher likelihood of undergoing PN with an open approach, higher-volume surgeons,
and younger patient age (P < .05). Surgeon subspecialty and US region were no
longer significant factors after guidelines publication. Number of PN normalized
to the incidence of RCC continued to increase over time (0.14%/y; R2 = 0.77; P <
.001). CONCLUSION: Partial nephrectomy in the post-guidelines era is no longer
confined to urological subspecialists or certain densely populated US regions.
Although rates of PN continue to increase relative to the recently decreasing
overall incidence of RCC, the slope has leveled off somewhat. This is likely
related to clinical intricacies of the best treatment modality and technologic
advances rather than changes related to guidelines publication.
PMID- 28410909
TI - Neoadjuvant Chemotherapy in Elderly Patients With Bladder Cancer: Oncologic
Outcomes From a Single Institution Experience.
AB - INTRODUCTION: We conducted this study to determine if, in appropriately selected
elderly patients receiving neoadjuvant chemotherapy (NAC), clinical outcomes
including pathologic complete response/downstaging and overall survival were
similar to a younger cohort. METHODS: Chart review was performed on patients
receiving NAC for urothelial carcinoma of the bladder (UCB) from 2004 to 2013. A
total of 116 patients were identified that underwent NAC from 2004 to 2013 for >=
cT2N0M0 UCB. Patients were excluded who received 2 cycles or less of chemotherapy
(N = 18; 11 patients in the younger cohort, 7 in the elderly group; P = .74).
Data was analyzed, and Kaplan-Meir analysis curves were used for survival and
recurrence. RESULTS: Forty-six elderly patients (age >= 70 years) (67% cisplatin
based regimen) were identified and compared with 70 (93% cisplatin-based regimen)
younger patients. The estimated glomerular filtration rate, performance status,
preoperative hemoglobin, and body mass index were significantly worse in elderly
patients. Dose reduction and pathologic downstaging to non-muscle-invasive
disease was not statistically different between older and younger patients
Complete pathologic response in older patients (16%) and in the younger cohort
(17%) were similar (P = .146). There was no significant difference in follow-up,
recurrence, or in median overall survival between patient groups (28 months
elderly vs. 35 months younger; P = .78). Age was not an independent predictor of
pathologic downstaging, complete response, overall survival, or recurrence-free
survival. CONCLUSIONS: NAC in elderly patients (>= 70 years old) demonstrated
equivalent toxicity and oncologic outcomes in our single-institution cohort.
Although older patients had significantly poorer performance status and renal
function, there were no differences in survival or response to NAC.
PMID- 28410910
TI - Heart Failure: A Paraneoplastic Manifestation of Renal Cell Carcinoma - Reversed
With Pazopanib.
PMID- 28410911
TI - Comprehensive Analysis of Survival Outcomes in Non-Clear Cell Renal Cell
Carcinoma Patients Treated in Clinical Trials.
AB - BACKGROUND: Clinical data from patients with non-clear cell renal cell carcinoma
(nccRCC) receiving targeted therapy are limited, and many clinical trials have
excluded these patients from study entry. We sought to investigate the outcomes
of patients with nccRCC treated in clinical trials in the modern era compared
with the outcomes of patients with clear cell RCC (ccRCC). PATIENTS AND METHODS:
We conducted a retrospective study of patients with metastatic RCC who had
received targeted therapy in Pfizer-sponsored phase II and III clinical trials
from 2003 to 2013. Associations between the histologic type and treatment outcome
(overall survival [OS] and progression-free survival [PFS]) were assessed using
the log-rank test on univariate analysis or the Wald chi2 test from Cox
regression on multivariable analysis, adjusted for baseline characteristics,
including age, sex, Eastern Cooperative Oncology Group performance status, body
mass index, International Metastatic RCC Database Consortium risk factors,
previous nephrectomy, previous therapy, metastatic sites, angiotensin system
inhibitor use, and statin use. RESULTS: We identified 4527 patients with
metastatic RCC: 4235 with ccRCC and 337 with nccRCC. Overall, the median OS was
shorter for those with nccRCC than for those with ccRCC (15.7 vs. 20.2 months;
hazard ratio [HR], 1.41; 95% confidence interval 1.22-1.63; P < .001). When
stratified by the International Metastatic RCC Database Consortium risk group,
the median OS was inferior for the intermediate- and poor-risk patients with
nccRCC than for those with ccRCC. However, no differences were found in the
favorable risk group for nccRCC versus ccRCC. The patients with nccRCC who had
received vascular endothelial growth factor-targeted therapy had shorter PFS
compared with that of ccRCC patients (median, 6.1 vs. 8.5 months; HR, 1.49; P <
.001) but similar PFS when treated with mammalian target of rapamycin inhibitors
(median, 4.3 vs. 4.4 months; HR, 0.92; P = .63). CONCLUSION: Our findings have
confirmed that patients with nccRCC are underrepresented in clinical trials and
highlight the need for further prospective studies exploring current and novel
agents for this patient population.
PMID- 28410913
TI - Superior mesenteric artery (SMA) resection during pancreatectomy for malignant
disease of the pancreas: a systematic review.
AB - BACKGROUND: Resection of the superior mesenteric artery (SMA) during
pancreatectomy is performed infrequently and is undertaken with the aim of
removing non-metastatic locally advanced pancreatic tumours. SMA resection
reports also encompass resection of other visceral vessels. The consequences of
resection of these different arteries are not necessarily equivalent. This is a
focused systematic review of the outcome of SMA resection during pancreatectomy
for cancer. METHODS: A computerized search of the English language literature was
undertaken for the period 1st January 2000 through 30th April 2016. The keywords
"Pancreatic surgery" and "Vascular resections" were used. Thirteen studies
reported 70 patients undergoing pancreatectomy with SMA resection from 10,726
undergoing pancreatectomy. Individual patient-level outcome data were available
for 25. RESULTS: Median (range) accrual period was 132 (48-372) months. Reported
peri-operative morbidity ranged from 39% to 91%. There were 5 peri-operative
deaths in the 25 patients with individual-outcome data. Median survival was 11
months (95% Confidence interval 9.5-12.5 months; standard error 0.8 months).
CONCLUSIONS: SMA resection during pancreatectomy is undertaken infrequently
incurring high peri-operative morbidity and mortality. Median survival is 11 (95%
CI 9.5-12.5) months. In contemporary practice there is no evidence to support SMA
resection during pancreatectomy.
PMID- 28410912
TI - Beyond Correlations, Sensitivities, and Specificities: Case Examples of the
Evaluation of Advanced Imaging in Oncology Clinical Trials and Cancer Treatment.
AB - Although advanced imaging is an important component of oncology clinical trials,
there has not been a lot of success in advancing its use from a research
perspective. One likely reason is the lack of consensus on the methodology used
to study advanced imaging in trials, which results in a disconcerted research
effort and produces data that are difficult to collate for use in validating the
imaging components being studied. Imaging is used in cancer clinical trials for
various indications, and the study design needed to evaluate the imaging in a
particular indication will vary. Through case examples, this paper will discuss
how advanced imaging is currently being investigated in oncology clinical trials,
categorized by the potential clinical indication for the imaging tool and offer
suggestions on how development should proceed to further evaluate imaging in the
given indication. Available National Cancer Institute resources that can assist
in this process will also be discussed.
PMID- 28410914
TI - Occult hepatitis B infection reactivation after ruxolitinib therapy.
PMID- 28410915
TI - Early hospital readmission in decompensated cirrhosis: Incidence, impact on
mortality, and predictive factors.
AB - BACKGROUND & AIMS: The early hospital readmission of patients with decompensated
cirrhosis is a current problem. A study is presented on the incidence, the impact
on mortality, and the predictive factors of early hospital readmission. PATIENTS
AND METHODS: On the study included 112 cirrhotic patients, discharged after some
decompensation between January 2013 and May 2014. Multivariate analyses were
performed to identify predictors of early readmission and mortality. RESULTS: The
early readmission rate was 29.5%. The predictive factors were male gender (OR:
2.81; 95% CI: 1.07-7.35), Model for End-Stage Liver Disease-sodium score >=15
(OR: 3.79; 95% CI 1.48-9.64), and Charlson index >=7 (OR: 4.34, 95% CI 1.65
11.4). This model enabled patients to be classified into low or high risk of
early readmissions (13.6% vs. 52.2%). The mortality rate was significantly higher
among patients with early readmission (73% vs. 35%) (p<.0001). After adjusting
for the Model for End-Stage Liver Disease-sodium score, Charlson index,
dependence in activities of daily living, educational status, and number of
medications on discharge, the early readmission was independently associated with
mortality. CONCLUSIONS: Early hospital readmission is common, and is
independently associated with mortality. Male gender, MELD-Na >=15, and Charlson
index >=7 are predictors of early readmission. These results could be used to
develop future strategies to reduce early readmission.
PMID- 28410916
TI - Chronic alcohol abuse in men alters bone mechanical properties by affecting both
tissue mechanical properties and microarchitectural parameters.
AB - OBJECTIVE OF THE STUDY: Alcohol-induced secondary osteoporosis in men has been
characterized by higher fracture prevalence and a modification of bone
microarchitecture. Chronic alcohol consumption impairs bone cell activity and
results in an increased fragility. A few studies highlighted effects of heavy
alcohol consumption on some microarchitectural parameters of trabecular bone. But
to date and to our knowledge, micro- and macro-mechanical properties of bone of
alcoholic subjects have not been investigated. PATIENTS: In the present study,
mechanical properties and microarchitecture of trabecular bone samples from the
iliac crest of alcoholic male patients (n=15) were analyzed and compared to a
control group (n=8). MATERIALS AND METHODS: Nanoindentation tests were performed
to determine the tissue's micromechanical properties, micro-computed tomography
was used to measure microarchitectural parameters, and numerical simulations
provided the apparent mechanical properties of the samples. RESULTS: Compared to
controls, bone tissue from alcoholic patients exhibited an increase of
micromechanical properties at tissue scale, a significant decrease of apparent
mechanical properties at sample scale, and significant changes in several
microarchitectural parameters. In particular, a crucial role of structure model
index (SMI) on mechanical properties was identified. CONCLUSIONS: 3D
microarchitectural parameters are at least as important as bone volume fraction
to predict bone fracture risk in the case of alcoholic patients.
PMID- 28410917
TI - The relative contribution of provider and ED-level factors to variation among the
top 15 reasons for ED admission.
AB - STUDY OBJECTIVE: We examine adult emergency department (ED) admission rates for
the top 15 most frequently admitted conditions, and assess the relative
contribution in admission rate variation attributable to the provider and
hospital. METHODS: This was a retrospective, cross-sectional study of ED
encounters (>=18years) from 19 EDs and 603 providers (January 2012-December
2013), linked to the Area Health Resources File for county-level information on
healthcare resources. "Hospital admission" was the outcome, a composite of
inpatient, observation, or intra-hospital transfer. We studied the 15 most
commonly admitted conditions, and calculated condition-specific risk-standardized
hospital admission rates (RSARs) using multi-level hierarchical generalized
linear models. We then decomposed the relative contribution of provider-level and
hospital-level variation for each condition. RESULTS: The top 15 conditions made
up 34% of encounters and 49% of admissions. After adjustment, the eight
conditions with the highest hospital-level variation were: 1) injuries, 2)
extremity fracture (except hip fracture), 3) skin infection, 4) lower respiratory
disease, 5) asthma/chronic obstructive pulmonary disease (A&C), 6) abdominal
pain, 7) fluid/electrolyte disorders, and 8) chest pain. Hospital-level intra
class correlation coefficients (ICC) ranged from 0.042 for A&C to 0.167 for
extremity fractures. Provider-level ICCs ranged from 0.026 for abdominal pain to
0.104 for chest pain. Several patient, hospital, and community factors were
associated with admission rates, but these varied across conditions. CONCLUSION:
For different conditions, there were different contributions to variation at the
hospital- and provider-level. These findings deserve consideration when designing
interventions to optimize admission decisions and in value-based payment
programs.
PMID- 28410918
TI - Comparison of UTI antibiograms stratified by ED patient disposition.
AB - OBJECTIVE: Institutional antibiograms guide Emergency Department (ED) clinicians'
empiric antibiotic selection. For this study, we created and compared
antibiograms of ED patients stratified by disposition (admitted or discharged).
METHODS: We conducted a cross-sectional study at two hospitals for 2014,
comparing antibiograms limited to Escherichia coli urinary tract infections.
Study-Specific Antibiograms, created for the study, excluded polymicrobial
samples and multiple cultures from the same patient. Study-Specific Antibiograms
were arranged by patient disposition: admitted (IP-Only) vs discharged from the
ED (ED-Only). Antibiogram data were presented as average antibiotic sensitivities
with 95% confidence intervals and demographic data as medians with interquartile
ranges. Sensitivities between Study-Specific Antibiograms were compared by
Fisher's Exact Test, alpha=0.05, 2 tails. RESULTS: For Hospital A, 13 antibiotics
were compared between Study-Specific ED-Only (n=313) vs IP-Only (n=244). We found
that sensitivities to all four antibiotics appropriate for empiric outpatient
therapy by Infectious Disease Society of America guidelines were significantly
(p<0.0001) higher in the ED-Only compared to IP-Only groups: ciprofloxacin 80%
(76-90%) vs 60% (53-69%), levofloxacin 81% (77-91%) vs 63% (57-72%),
nitrofurantoin 75% (70-84%) vs 51% (44-58%), and trimethoprim/sulfamethoxazole
73% (68-82%) vs 58% (52-67%). For Hospital B, 14 antibiotics were compared
between Study-Specific ED-Only (n=256) and IP-Only (n=168). Two out of the five
appropriate empiric outpatient antibiotics had significantly (p<0.0001) higher
sensitivities for ED-Only compared to IP-Only: ciprofloxacin 87% (83-91%) vs 71%
(64-78%) and levofloxacin 86% (82-91%) vs 71% (65-78%). CONCLUSIONS: We found
higher antibiotic sensitivities in ED-Only than the IP-Only Study-Specific
Antibiograms. Our Study-Specific Antibiograms offer an alternative guide for
antibiotic selection in the ED.
PMID- 28410920
TI - Potential drug interaction with opioid agonist in the setting of chronic low-dose
opioid antagonist use.
AB - Low dose naltrexone (LDN) has been evaluated in several small studies for the
treatment of inflammatory conditions. It is thought to work through modulation of
inflammatory mediators and upregulation of endogenous opioid receptors. This may
hypersensitize patients to exogenous opioids. Drug-drug interaction screening
tools built into electronic health records and other services identify the
interaction as risk of opioid withdrawal rather than hypersensitivity. We present
a case of a drug-drug interaction in a patient who was receiving LDN treatment of
multiple sclerosis. The patient received a single dose of oxycodone 5mg that
resulted in obtundation unresponsive to painful stimuli necessitating the
administration of naloxone boluses and infusion along with admission to the
intensive care unit for 1 night. The patient responded well to naloxone therapy.
He was discharged in satisfactory condition.
PMID- 28410919
TI - Factors associated with hospital admission after an emergency department treat
and release visit for older adults with injuries.
AB - INTRODUCTION: Emergency Department (ED) visits for injury often precede hospital
admissions in older adults, but risk factors for these admissions are poorly
characterized. We sought to determine the incidence and risk factors for
hospitalization shortly following discharge home from an ED visit for traumatic
injury in older adults. We hypothesized higher risk for admission in those with
increased age, discharged home after falls, with increased comorbidity burden,
and who live in poor neighborhoods. METHODS: We identified all community-dwelling
patients >=65years old treated and released for traumatic injury at non-federal
EDs in Florida using the 2011 State Inpatient Database and State ED Database of
the Agency for Healthcare Research and Quality. Outcome measures were
hospitalization within 9 and 30days of discharge from the ED. Multivariable
logistic regression was used to establish independent risk factors for hospital
admission. RESULTS: Of 163,851 index ED injury visits, 6298 (3.8%) resulted in
inpatient admissions within 9days and 12,938 (7.9%) within 30days. Factors
associated with increased odds of admission within 9days included: each
additional comorbidity, >=moderate injury to abdomen or pelvis/extremities, and
median neighborhood income<$39,000. Additional factors associated with increased
odds of admission within 30days included: lack of private insurance supplement
and median neighborhood income<$48,000. CONCLUSION: Among older adults treated
and discharged from the ED for an injury, those who have high comorbidity
burdens, have abdominal or orthopedic injuries, and live in poor neighborhoods
are at increased risk of hospitalization within 9 or 30days of ED discharge.
PMID- 28410921
TI - A randomized trial to determine the impact of a digestion resistant starch
composition on the gut microbiome in older and mid-age adults.
AB - BACKGROUND: The elderly often have a diet lacking resistant starch (RS) which is
thought to lead to gut microbiome dysbiosis that may result in deterioration of
gut colonocytes. OBJECTIVE: The primary objective was to assess if elderly (ELD;
>= 70 years age) had microbiome dysbiosis compared to mid-age (MID; 30-50 years
age) adults and then determine the impact of daily consumption of MSPrebiotic(r)
(a RS) or placebo over 3 months on gut microbiome composition. Secondary
objectives included assessment of stool short-chain fatty acids (SCFA) and
inflammatory markers in ELD and MID Canadian adults. DESIGN: This was a
prospective, placebo controlled, randomized, double-blinded study. Stool was
collected at enrollment and 6, 10 and 14 weeks after randomization to placebo or
MSPrebiotic(r). Microbiome analysis was done using 16S rRNA sequencing of DNA
extracted from stool. SCFA analysis of stool was performed using gas
chromatography. RESULTS: There were 42 ELD and 42 MID participants randomized to
either placebo or MSPrebiotic(r) who completed the study. There was significantly
higher abundance of Proteobacteria (Escherichia coli/Shigella) in ELD compared to
MID at enrollment (p < 0.001) that was not observed after 12 weeks of
MSPrebiotic(r) consumption. There was a significant increase in Bifidobacterium
in both ELD and MID compared to placebo (p = 0.047 and 0.006, respectively).
There was a small but significant increase in the stool SCFA butyrate levels in
the ELD on MSPrebiotic(r) versus placebo. CONCLUSIONS: The study data
demonstrated that MSPrebiotic(r) meets the criteria of a prebiotic and can
stimulate an increased abundance of endogenous Bifidobacteria in both ELD and MID
without additional probiotic supplementation. MSPrebiotic(r) consumption also
eliminated the dysbiosis of gut Proteobacteria observed in ELD at baseline.
CLINICAL TRIAL REGISTRY NUMBER: NCT01977183 listed on NIH website:
ClinicalTrials.gov. The full trial protocol is available on request from the
corresponding author. NUCLEOTIDE SEQUENCE ACCESSION NUMBERS: The 16S rRNA
sequencing data and metadata generated in this study have been submitted to the
NCBI Sequence Read Archive (SRA: http://www.ncbi.nlm.nih.gov/bioproject/381931).
PMID- 28410922
TI - Antioxidant response to artichoke leaf extract supplementation in metabolic
syndrome: A double-blind placebo-controlled randomized clinical trial.
AB - BACKGROUND: Oxidative stress is associated with most components and complications
of Metabolic Syndrome (MetS). Artichoke Leaf Extract (ALE) has demonstrated anti
oxidant properties in both laboratory and animal studies. AIM: This study was
designed to examine the effects of ALE on oxidative stress indices in patients
with MetS. METHODS: In the current double-blind placebo-controlled randomized
clinical trial, 80 patients with MetS were randomly allocated to either "ALE
group" (received 1800 mg ALE as four tablets per day) or "Placebo group"
(received placebo containing cornstarch, lactose and avicel as four tablets per
day) for 12 weeks. Serum levels of malondialdehyde (MDA), total antioxidant
capacity (TAC), oxidized-LDL (ox-LDL), red blood cell glutathione peroxidase
(GPx) and superoxidase dismutase (SOD), as well as dietary intakes were assessed
at baseline and at the end of the study. RESULTS: A total number of 68 patients
completed the study (ALE group = 33; placebo group = 35). Dietary intakes of
energy, macronutrients, and micronutrients were not significantly different
between two groups throughout the trial, with the exception of zinc (p < 0.05).
The concentration of ox-LDL decreased significantly in ALE group in comparison to
the placebo group (-266.8 +/- 615.9 vs -129.5 +/- 591.2 ng/L; p < 0.05). However,
no significant inter- and intra-group changes in MDA, SOD, GPx, and TAC
concentrations were observed. CONCLUSION: ALE decreased serum ox-LDL level in
patients with MetS, with no beneficial effects on other antioxidant indices.
CLINICAL TRIAL REGISTRATION NUMBER: IRCT201409033320N9.
PMID- 28410923
TI - Infrarenal endograft clamping in late open conversions after endovascular
abdominal aneurysm repair.
AB - OBJECTIVE: The aim of this study was to report the technical aspects and outcomes
of late open conversion (LOC) after endovascular aneurysm repair (EVAR) in a
single center by using exclusively infrarenal clamping of the endograft as an
alternative to suprarenal or supraceliac aortic clamping. METHODS: A
retrospective analysis of EVAR requiring late explantation (>30 days) from
January 1996 to October 2016 was performed. Patients' demographics, type of
endograft, duration of implantation, reason for removal, extent of stent graft
removal, type of reconstruction, 30-day mortality, postoperative complications,
and long-term survival were obtained for analysis. RESULTS: During the study
period, 28 patients required LOC. The mean age at conversion was 75.11 +/- 6.65
years; 26 of 28 (92.86%) were male. Grafts were excised after a median of 41.4
months (range, 5.97-112.67 months), with 21 of 28 explantations (75%) performed
electively. Multiple types of EVAR devices have been explanted; suprarenal
fixation was present in 75% of the cases. The indication for LOC was the presence
of an endoleak in 27 cases (20 type I, 4 type II associated with aneurysm growth,
3 type III, and 3 endotensions; in 3 cases, multiple types of endoleak were
present) and graft thrombosis in 1 case. All patients underwent a transperitoneal
approach with infrarenal clamping. No patient required revascularization of
visceral or renal vessels. Complete removal of the stent graft was performed in 8
of 28 cases, partial removal in the remaining 20 cases (with conservation of the
proximal portion in 16 of 20 cases). Technical success was 100%. Overall 30-day
mortality was 7.14% (2/28). The 30-day mortality was 9.5% in elective patients
and 0% in the urgent setting; this difference was not statistically significant
(P = .56). Postoperative kidney injury rate was 7.7% (2/26). Mean follow-up was
47.37 +/- 55.67 months (range, 0.23-175.07 months). The estimated 5-year survival
rate was 78%. No aneurysm-related death or additional procedure occurred during
follow-up. CONCLUSIONS: LOC after EVAR using infrarenal clamping of the endograft
is a feasible and effective technique, with satisfactory postoperative mortality
and morbidity. This method allows simplification of the surgical technique and
may avoid renal and visceral complications related to suprarenal or supraceliac
clamping.
PMID- 28410924
TI - Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score
correlates with the intensity of multimodal limb treatment and patient-centered
outcomes in patients with threatened limbs managed in a limb preservation center.
AB - OBJECTIVE: The Society for Vascular Surgery Wound, Ischemia, foot Infection
(WIfI) system aims to stratify threatened limbs according to their anticipated
natural history and estimate the likelihood of benefit from revascularization,
but whether it accurately stratifies outcomes in limbs undergoing aggressive
treatment for limb salvage is unknown. We investigated whether the WIfI stage
correlated with the intensity of limb treatment required and patient-centered
outcomes. METHODS: We stratified limbs from a prospectively maintained database
of consecutive patients referred to a limb preservation center according to WIfI
stage (October 2013-May 2015). Comorbidities, multimodal limb treatment,
including foot operations and revascularization, and patient-centered outcomes
(wound healing, limb salvage, amputation-free survival, maintenance of ambulatory
and independent living status, and mortality) were compared among WIfI stages.
Multivariate analysis was performed to identify predictors of wound healing and
limb salvage. RESULTS: We identified 280 threatened limbs encompassing all WIfI
stages in 257 consecutive patients: stage 1, 48 (17%); stage 2, 67 (24%); stage
3, 64 (23%); stage 4, 83 (30%); and stage 5 (unsalvageable), 18 (6%). Operative
foot debridement, minor amputation, and use of revascularization increased with
increasing WIfI stage (P <= .04). Revascularization was performed in 106 limbs
(39%), with equal use of open and endovascular procedures. Over a median follow
up of 209 days (interquartile range, 95, 340) days, 1-year Kaplan-Meier wound
healing cumulative incidence was 71%, and the proportion with complete wound
healing decreased with increasing WIfI stage. Major amputation was required in 26
stage 1 to 4 limbs (10%). Increasing WIfI stage was associated with decreased 1
year Kaplan-Meier limb salvage (stage 1: 96%, stage 2: 84%, stage 3: 90%, and
stage 4: 78%; P = .003) and amputation-free survival (P = .006). Stage 4 WIfI
independently predicted amputation (hazard ratio, 12; 95% confidence interval,
1.6-94). Amputation rates in patients with severe Ischemia grade 3 were lower in
those who underwent revascularization than in those who did not (14% vs 41%; P =
.01) Ambulatory and independent living status at follow-up deteriorated
significantly from baseline in stage 4 but not stage 1 to 3 patients. Mortality
was not different between WIfI stages. CONCLUSIONS: In patients treated
aggressively for limb salvage, WIfI stage correlated with intensity of multimodal
limb treatment and with limb salvage and patient-centered outcomes at 1 year.
Revascularization improved limb salvage in severe ischemia. These data support
the Society for Vascular Surgery WIfI system as a powerful tool to risk-stratify
patients with threatened limbs and guide treatment.
PMID- 28410925
TI - Circulating osteocalcin is unrelated to glucose homoeostasis in adults with type
1 diabetes.
AB - AIMS: To assess the relationship between total osteocalcin (tOC),
undercarboxylated osteocalcin (ucOC) and a range of markers of glucose
homeostasis in type 1 diabetes. METHODS: One hundred and eight community-based
Caucasian adults (53 males, 55 females) without a history of osteoporosis and
with a mean+/-SD age 39.1+/-15.1years and median [inter-quartile range] type 1
diabetes duration of 14.3 [6.6-20.4] years participated in a cross-sectional
study of bone health. Fasting serum glucose and HbA1c, and serum tOC, ucOC, total
adiponectin and procollagen type 1N-terminal propeptide (P1NP) were measured
using validated assays, and daily insulin dose and estimated glucose disposal
rate (eGDR) were calculated. Multiple linear regression was used to determine
independent associates of markers of glucose homoeostasis (HbA1c, fasting serum
glucose, daily insulin dose, eGDR and serum total adiponectin). RESULTS: In sex
adjusted multivariable regression analyses, ln(serum P1NP) was independently and
inversely associated with ln(HbA1c) and ln(serum adiponectin) (P<=0.013). Other
associations included those between ln(serum vitamin D) and ln(HbA1c)
(inversely), daily insulin dose (inversely) and eGDR (positively) (P<=0.035), as
well as an inverse relationship between overweight by waist circumference and
ln(serum adiponectin) (P<0.001). Ln(serum tOC) and ln(serum ucOC) were not
independently associated with any glucose homoeostasis marker. CONCLUSIONS: These
data from well characterized community-based adults with type 1 diabetes do not
suggest that there is a role for osteocalcin in the potentially complex interplay
between the skeleton and energy homoeostasis in type 1 diabetes.
PMID- 28410926
TI - Effect of high density lipoprotein cholesterol on the relationship of serum iron
and hemoglobin with kidney function in diabetes.
AB - Findings of increased hemoglobin inside the HDL proteome among persons with
diabetes who have haptoglobin 2-2 genotype suggest that iron-induced lipid
peroxidation may be involved in diabetic kidney disease. We investigated the
relationships of serum hemoglobin and iron with kidney function, and whether this
varied by level of HDLc, in 5296 adults with and 49,161 without diabetes.
Estimated eGFR was our marker of kidney function. Hemoglobin was positively
associated with eGFR among those with diabetes and inversely among those without
diabetes (interaction p-value <0.0001). Iron was inversely associated with eGFR
regardless of diabetes status. When stratified by median HDLc and median
hemoglobin, among persons with diabetes mean eGFR was highest in those with high
hemoglobin and low HDLc and lowest in those with both low hemoglobin and low
HDLc. This divergent relationship was not observed in the non-diabetic
population. In contrast to hemoglobin, high iron and low HDLc were associated
with a lower mean eGFR regardless of diabetes status. Our data suggest that among
persons with diabetes, both hemoglobin and iron are harmful to kidney function at
high levels. Our data also suggest that HDLc may play a role in the relationship
of high hemoglobin in kidney function in diabetes.
PMID- 28410927
TI - Younger-onset versus older-onset type 2 diabetes: Clinical profile and
complications.
AB - AIMS: To compare the clinical profile and complications between younger and older
onset type 2 diabetes (T2DM) patients at a tertiary care diabetes center in south
India. METHODS: We compared individuals with T2DM detected at age <=25years
(n=267) and at age>=50years (n=267), matched for gender and duration of diabetes.
We reviewed electronic patient charts and extracted data on biochemical
parameters (plasma glucose, serum lipids and glycated hemoglobin). We estimated
prevalence of complications (retinopathy, nephropathy, neuropathy, and peripheral
vascular disease). We examined odds of having each complication, after adjusting
for clinical differences between younger- and older-onset T2DM. RESULTS:
Individuals with younger-onset T2DM had significantly greater glycated hemoglobin
(8.7 vs. 7.5%), serum cholesterol (160 vs. 148mg/dl), serum triglycerides (147
vs. 128mg/dl), LDL cholesterol (92 vs. 82mg/dl) and lower HDL cholesterol levels
(39 vs. 42mg/dl). However, waist circumference (90.4 vs. 92.6cm) and systolic
blood pressure (125 vs. 133mmHg) were significantly higher in older onset T2DM.
Prevalence of retinopathy (47.6 vs. 31.0%) was higher in younger onset T2DM while
neuropathy (41.8 vs. 9.2%) and peripheral vascular disease (6.2 vs. 1.2%) were
higher in older onset T2DM. In multiple logistic regression analysis, after
adjusting for glycated hemoglobin, hypertension, and hypercholesterolemia,
younger onset T2DM had a higher odds of developing retinopathy [Odds Ratio: 2.19;
Confidence Intervals: 1.42-3.38] when compared to older onset T2DM. CONCLUSIONS:
Younger onset T2DM patients have worse glycemic and lipid control, and higher
prevalence of retinopathy compared to older onset T2DM patients. This underscores
the need for more aggressive metabolic control in young-onset T2DM.
PMID- 28410928
TI - Letter.
PMID- 28410929
TI - Applying ethical principles in discussing SUDEP with patients and families.
PMID- 28410930
TI - Ligand diffusion in proteins via enhanced sampling in molecular dynamics.
AB - Computational simulations in biophysics describe the dynamics and functions of
biological macromolecules at the atomic level. Among motions particularly
important for life are the transport processes in heterogeneous media. The
process of ligand diffusion inside proteins is an example of a complex rare event
that can be modeled using molecular dynamics simulations. The study of physical
interactions between a ligand and its biological target is of paramount
importance for the design of novel drugs and enzymes. Unfortunately, the process
of ligand diffusion is difficult to study experimentally. The need for
identifying the ligand egress pathways and understanding how ligands migrate
through protein tunnels has spurred the development of several methodological
approaches to this problem. The complex topology of protein channels and the
transient nature of the ligand passage pose difficulties in the modeling of the
ligand entry/escape pathways by canonical molecular dynamics simulations. In this
review, we report a methodology involving a reconstruction of the ligand
diffusion reaction coordinates and the free-energy profiles along these reaction
coordinates using enhanced sampling of conformational space. We illustrate the
above methods on several ligand-protein systems, including cytochromes and G
protein-coupled receptors. The methods are general and may be adopted to other
transport processes in living matter.
PMID- 28410931
TI - A model of recovery from inhalation injury and cutaneous burn in ambulatory
swine.
AB - Inhalation injury commonly accompanies thermal injury, increasing the likelihood
of mortality and multiple organ dysfunction (MOD). Large animal models have given
important insight into the pathophysiology of this injury; however recapitulating
late MOD has remained difficult. The current report describes experiments using a
smoke inhalation and burn model, with follow-up of ambulatory swine for 14days
with bronchoscopy, CT scanning, and bronchoalveolar lavage fluid (BALF)/blood
collection. Clinically, animals cleared airway damage in the first several days
after-injury. This was mirrored with erythematous airways on day 2 after-injury,
which resolved by the end of the experiment, as did parenchymal damage seen on
CT. An initial rise in the protein content of BALF immediately after-injury was
followed by a dramatic increase in the concentration of leukocytes. Circulating
neutrophils increased while lymphocytes decreased; both correlated with cell
counts in BALF. IL8 levels in BALF increased 30-fold and remained elevated
throughout the experiment. IL1ra increased circulation immediately after-injury,
and afterwards in BALF. Other cytokines (TNFalpha, IL12) transiently increased in
BALF (and decreased in circulation) on day 2. Taken together, these results
display a remarkable capability for the lungs to recover in the absence of
intubation, with further evidence of the role of cytokines such as IL8 and IL1ra.
The possible exacerbating effects of clinical practices such as ventilation and
bronchoscopies should be considered.
PMID- 28410932
TI - Outcome analysis of colistin-treated burn center patients.
AB - OBJECTIVES: Intravenous colistimethate sodium (CMS) use in burn center patients
is increasing due to the emergence of multidrug-resistant gram-negative bacteria.
However, optimal dosing strategies and factors that may contribute to treatment
failure are limited. The purpose of this study was to determine factors that may
contribute to treatment failure in colistin-treated burn center patients.
METHODS: This retrospective, observational study included burn center patients
that received >=48h of intravenous CMS between June 1, 2009 and June 30, 2014.
Data was collected utilizing the institution's electronic medical record system.
Statistical analysis included demographic, univariable, and multivariable
analysis to determine factors that may predict clinical failure of burn center
patients requiring intravenous CMS. RESULTS: Eighty-one patients were included in
this study, with 55 patients (68%) achieving clinical success. A total daily dose
(TDD) of >5mg/kg ideal body weight (IBW) was associated with significantly less
clinical failure (odds ratio=0.21; 95% CI, 0.05, 0.91). Additionally, clinical
failure was significantly higher in patients with wounds as the primary source of
infection, creatinine clearances of 91-120mL/min, and those receiving renal
replacement therapy. No difference was observed in nephrotoxicity when comparing
TDD >5mg/kg IBW and TDD <=5mg/kg IBW. CONCLUSIONS: Clinical success was
significantly higher with larger intravenous CMS doses in burn center patients.
Higher CMS doses were not found to be associated with increased nephrotoxicity
within this patient group.
PMID- 28410933
TI - The role of complement in the acute phase response after burns.
AB - Severe burns induce a complex systemic inflammatory response characterized by a
typical prolonged acute phase response (APR) that starts approximately 4-8h after
burn and persists for months up to a year after the initial burn trauma. During
this APR, acute phase proteins (APPs), including C-reactive protein (CRP) and
complement (e.g. C3, C4 and C5) are released in the blood, resulting amongst
others, in the recruitment and migration of inflammatory cells. Although the APR
is necessary for proper wound healing, a prolonged APR can induce local tissue
damage, hamper the healing process and cause negative systemic effects in several
organs, including the heart, lungs, kidney and the central nervous system. In
this review, we will discuss the role of the APR in burns with a specific focus
on complement.
PMID- 28410934
TI - Holistic burn care: Survival and beyond.
PMID- 28410935
TI - Erratum to "Inhibition of cancer migration and invasion by knocking down delta-5
desaturase in COX-2 overexpressed cancer cells" [Redox Biol. 11 (2017) 653-662].
PMID- 28410936
TI - Radiographic and Clinical Analysis of Lateral Epicondylitis.
AB - PURPOSE: The literature suggests that radiographs may be unnecessary in the
initial evaluation of lateral epicondylitis because treatment is rarely altered
as a result of the radiographic findings. The most commonly reported radiographic
finding is calcification at the lateral epicondyle. Our goal was to perform a
quantitative and qualitative analysis of this finding to determine its importance
and possible relationship with various clinical factors and patient-reported
measures. METHODS: All patients diagnosed with lateral epicondylitis by a single
surgeon during a 5-year period were retrospectively reviewed. Age, sex,
laterality, hand dominance, pain visual analog scale, duration of symptoms, Quick
Disability of the Arm, Shoulder, and Hand questionnaire score, and history of
steroid injection were recorded. Calcifications on standard elbow radiographs,
acquired digitally and viewed at 200% magnification on a 24-inch monitor, were
characterized by size and relationship with the lateral epicondyle. RESULTS: We
reviewed 245 patients diagnosed with lateral epicondylitis. A total of 115 elbows
(47%) demonstrated lateral epicondyle calcifications. Patients with and without
calcifications were similar with regard to clinical factors, as were patients
with larger or smaller lesions. Eighty-five elbows (35%) had additional
radiographic findings. Treatment was not altered by the radiographic findings in
any case. CONCLUSIONS: Lateral epicondyle calcifications are much more common in
lateral epicondylitis than previously reported, possibly owing to modern digital
radiography and magnification, although they do not appear to be related to
clinical factors including patient-reported measures. Thus, patients and surgeons
should be careful to avoid overinterpretation of such findings. Although
radiographs may be helpful in ruling out additional pathology, we did not find
other clinically important contributions to the initial evaluation and management
of this condition, and thus we do not recommend their routine use. TYPE OF
STUDY/LEVEL OF EVIDENCE: Diagnostic IV.
PMID- 28410937
TI - Proximal Row Carpectomy and 4-Corner Arthrodesis in Patients Younger Than Age 45
Years.
AB - PURPOSE: To examine the long-term outcome of patients aged less than 45 years who
underwent either proximal row carpectomy (PRC) or 4-corner arthrodesis (4CA) for
wrist arthritis. METHODS: We reviewed a retrospective cohort of 89 patients aged
less than 45 years who underwent either 4CA (n = 51) or PRC (n = 38) for wrist
arthritis. Mean follow-up was 11 years in the 4CA group and 18 years in the PRC
group. RESULTS: Overall, there were no differences between groups in the need for
revision surgery. Complications included 6 nonunions in the 4CA group (12%), 1
infection in each group, and 11 patients who experienced radiocarpal impingement
(8 4CA and 3 PRC). There was no difference in the number of patients reporting
moderate or severe pain between the PRC and 4CA groups. Mean flexion-extension
arc was 54 degrees after 4CA, compared with 73 degrees after PRC. Patients who
underwent 4CA had slightly improved grip strength (65% of the opposite side)
compared with those who had PRC (54%). Mean postoperative Disabilities of the
Arm, Shoulder, and Hand questionnaire scores were 32 versus 19 (PRC vs 4CA) and
patient-rated wrist evaluation scores were 27 versus 28 (PRC vs 4CA). Comparing
radiographic arthritis, the 10-year outcome, free of moderate/severe arthritis
for the PRC and 4CA groups, was 70% and 71%, respectively. CONCLUSIONS: Both PRC
and 4CA represent a good surgical option for young patients with wrist arthritis,
with similar complication rates, postoperative pain levels, wrist function, and
long-term outcomes free of arthrodesis. Proximal row carpectomy has improved
motion and fewer complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 28410939
TI - Acute Hand Ischemia Following Elective Venous Sclerotherapy for Dorsal Hand
Varicose Veins.
AB - Venous sclerotherapy is an emerging cosmetic treatment option for dorsal hand
varicose veins. Although venous sclerotherapy is considered a safe and effective
procedure for treatment of venous malformations and varicosities in both the
upper and lower extremities, inadvertent injection of the sclerosing agent into
the arterial system has led to reported instances of acute ischemic events and
distal limb necrosis. This is a rare but well-documented complication of lower
extremity venous sclerotherapy. Only 2 cases have been reported in upper
extremity venous sclerotherapy, both of which occurred during treatment of
complex vascular malformations. We report an instance of acute, distal digit
ischemia after elective venous sclerotherapy for a dorsal hand varicosity. As
this procedure grows in popularity, it is essential for hand surgeons to be aware
of this rare but potentially devastating complication.
PMID- 28410938
TI - Preservation of Devitalized Bone in Necrotic Digits Following Crush Injury With
Free Tissue Transfer.
AB - Traditional management of necrotic digits has been to allow demarcation between
viable and nonviable tissues to occur, and thus to indicate the level of
amputation required. In this case report, the phalangeal length of the necrotic
thumb was maintained in 2 patients who had sustained crush injury. After
nonviable soft tissues were debrided, the devitalized bones were covered with
soft tissue flaps. All wounds healed without infection. Both cosmetic and
functional results of the reconstructed thumbs were satisfactory. In one patient,
radiographs of the thumb demonstrated resorption of the distal phalanx, but this
did not impede daily use. This experience supports an earlier observation
suggesting that devitalized bone can be covered for salvage in some cases.
PMID- 28410940
TI - Stability of different influenza subtypes: How can high hydrostatic pressure be a
useful tool for vaccine development?
AB - BACKGROUND: Avian influenza A viruses can cross naturally into mammals and cause
severe diseases, as observed for H5N1. The high lethality of human infections
causes major concerns about the real risk of a possible pandemic of severe
diseases to which human susceptibility may be high and universal. High
hydrostatic pressure (HHP) is a valuable tool for studies regarding the folding
of proteins and the assembly of macromolecular structures such as viruses;
furthermore, HHP has already been demonstrated to promote viral inactivation.
METHODS: Here, we investigated the structural stability of avian and human
influenza viruses using spectroscopic and light-scattering techniques. We found
that both particles have similar structural stabilities and that HHP promotes
structural changes. RESULTS: HHP induced slight structural changes to both human
and avian influenza viruses, and these changes were largely reversible when the
pressure returned to its initial level. The spectroscopic data showed that H3N2
was more pressure-sensitive than H3N8. Structural changes did not predict changes
in protein function, as H3N2 fusion activity was not affected, while H3N8 fusion
activity drastically decreased. The fusion activity of H1N1 was also strongly
affected by HHP. In all cases, HHP caused inactivation of the different influenza
viruses. CONCLUSIONS: HHP may be a useful tool for vaccine development, as it
induces minor and reversible structural changes that may be associated with
partial preservation of viral biological activities and may potentiate their
immunogenic response while abolishing their infectivity. We also confirmed that,
although pressure does not promote drastic changes in viral particle structure,
it can distinctly affect viral fusion activity.
PMID- 28410941
TI - Potentiometric, UV and 1H NMR study on the interaction of Cu2+ with ampicillin
and amoxicillin in aqueous solution.
AB - A potentiometric, UV and 1H NMR study on Cu2+-ampicillin [(2S,5R,6R)-6-([(2R)-2
amino-2-phenylacetyl]amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane
2-carboxylic acid] and -amoxicillin [(2S,5R,6R)-6-{[(2R)-2-amino-2-(4
hydroxyphenyl)-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane
24-carboxylic acid] systems in NaCl aqueous solution at I=0.15molL-1 and t=25
degrees C is reported. On the basis of potentiometric results two speciation
models were proposed for each system. It was found that spectrophotometric and 1H
NMR measurements are essential for selecting the most reliable speciation models.
They included ML, MLOH and ML(OH)2 species in both systems and, only for Cu2+
ampicillin, also MLH species. The stability constants obtained by UV and 1H NMR
titrations were comparable to the ones calculated by potentiometry. The
sequestering ability of the ligands under study towards Cu2+ by pL0.5 empiric
parameter (ligand concentration required to sequester 50% of the metal cation
present in traces) at several pH values was calculated as well. For ampicillin
and amoxicillin, pL0.5=7.19 and 6.67, respectively, at physiological pH,
I=0.15molL-1 and t=25 degrees C were obtained.
PMID- 28410942
TI - Effect of pressure on bilayer phase behavior of N-methylated di-O
hexadecylphosphatidylethanolamines: relevance of head-group modification on the
bilayer interdigitation.
AB - The phase transitions of N-methylated di-O-hexadecylphosphatidylethanolamines
(DHPE, DH-N-methyl-PE (DHMePE) and DH-N,N-dimethyl-PE (DHMe2PE)) were observed by
differential scanning calorimetry (DSC) and fluorometry under atmospheric
pressure and by light-transmittance measurements under high pressure. The DSC
thermograms showed that the N-methylated DHPE bilayers underwent the phase
transition from the gel phase to the liquid crystalline (Lalpha) phase under
atmospheric pressure. The gel phase was identified by fluorometry as the lamellar
gel (Lbeta) phase, and not interdigitated gel (LbetaI) phase. The gel/Lalpha
transition temperature increased with pressure while decreased stepwise with
increasing polar head-group size. This stepwise depression of the transition
temperature may be caused by the inverse-proportional hydrogen-bonding
capabilities of the head-group to the head-group size. The thermodynamic
quantities of the gel/Lalpha transition were comparable for the N-methylated DHPE
bilayers. The pressure-induced LbetaI phase was not found in these bilayers
although the bilayer of di-O-hexadecylphosphatidylcholine (DHPC), which is a kind
of N-methylated DHPEs, forms the LbetaI phase only by hydration under atmospheric
pressure. Taking into account that the bilayers of diacyl-homologs of N
methylated DHPEs, N-methylated dipalmitoyl-PEs except for
dipalmitoylphosphatidylcholine (DPPC), do not form the LbetaI phase in the whole
pressure range investigated but the DPPC bilayer forms the LbetaI phase under
high pressure, we can say that the interdigitation requires weaker interaction
between large-sized head groups like the bulky choline group.
PMID- 28410943
TI - Efficacy of single-stage and two-stage Fowler-Stephens laparoscopic orchidopexy
in the treatment of intraabdominal high testis.
AB - BACKGROUND/OBJECTIVE: To compare the curative effect of single-stage and two
stage Fowler-Stephens (F-S) laparoscopic orchidopexy for intraabdominal high
testis and explore the appropriate surgical approach. METHODS: We performed a
prospective analysis of the clinical data of 28 patients who underwent F-S
laparoscopic orchidopexy for intraabdominal high testis in our department from
May 2012 to April 2015, including 15 cases of the single-stage F-S operation and
13 cases of the two-stage F-S operation. By comparing the two groups preoperative
and postoperative (6 months) clinical data of testicular position, testicular
volume, and sex hormone levels [testosterone (T), follicle stimulating hormone
(FSH), and estradiol (E2)], we analyzed the difference in efficacy between the
two procedures. RESULTS: Twenty-eight patients completed laparoscopic surgery, no
case was converted, and no testis was excised. All patients were followed up for
9-25 months after the operation, with an average follow-up of 16.2 months. The
postoperative testicular volume of the single-stage and two-stage F-S groups was
not significantly reduced (p>0.05). In both groups, the postoperative T levels
were significantly increased compared to the preoperative levels (p<0.05), while
the FSH and E2 levels were significantly decreased (p<0.05). The differences in
testicular volume and T, FSH, and E2 levels between the two surgical procedures
were not significant (p>0.05). In the single-stage F-S group, the testes were
located in the scrotum in 13 cases and retracted to the lower groin in two cases.
In the two-stage F-S group, the testes were located in the scrotum in 12 cases
and retracted to the lower groin in one case. The difference in postoperative
testicular position between the two groups was not significant (p>0.05).
CONCLUSION: In the case of testis with good collateral circulation, single-stage
F-S laparoscopic orchidopexy had the same safety and efficacy as the two-stage F
S procedure. Surgical options should be based on comprehensive consideration of
intraoperative testicular location, testicular ischemia test, and collateral
circumstances surrounding the testes. Under the appropriate conditions, we
propose single-stage F-S laparoscopic orchidopexy be preferred. It may be
appropriate to avoid unnecessary application of the two-stage procedure that has
a higher cost and causes more pain for patients.
PMID- 28410944
TI - [Asthma control in patients attending primary care in Spain (Actis study)].
AB - OBJECTIVE: To assess prevalence of non controlled (ACT- Asthma Control Test<20)
asthma in real world clinical practice in Spain. DESIGN: Observational, cross
sectional study. LOCATION: 58 primary care centers from 13 Autonomous
Communities. PARTICIPANTS: Asthma patients attending physicians office to collect
repeat prescriptions for continuous treatment (Group A), or due to symptoms
worsening (Group B). MAIN MEASUREMENTS: Socio-demographic characteristics (age,
gender, education, smoking history), physician's assessment of asthma severity,
current treatment for asthma, co-morbidities, healthcare-related resources
utilization (primary care or emergency visits, hospitalizations), labour or
school absenteeism, ACT score and treatment adherence. RESULTS: 376 patients from
group A and 262 from group B were included, 59% female, mean age 45 years, 21%
smokers and time since asthma diagnosis 8.9 years. 87% were on short acting beta
2 agonists, 62% long acting beta-2 agonists with inhaled corticosteroids and
13.8% regular inhaled corticosteroids. Poor asthma control was observed in 75.6%
from group B and 23.8% from group A; only 5.3% from group A showed total asthma
control (ACT=25). Poorer asthma control was significantly associated with longer
disease duration and higher use of resources. CONCLUSIONS: Prevalence of poor
asthma control among patients attending due to symptoms worsening continues to be
very high even in patients who come to renew their prescription. Poor asthma
control is associated to high use of resources and high impact on burden of
disease.
PMID- 28410945
TI - Diagnostic Approach in Fetal Coarctation of the Aorta: A Cost-Utility Analysis.
AB - BACKGROUND: Coarctation of the aorta (CoA) is difficult to diagnose by fetal
echocardiogram (F-Echo), often requiring multiple F-Echos during gestation and
neonatal echocardiograms (N-Echos) after birth. Furthermore, CoA is the most
common ductal-dependent lesion missed on routine physical exam. OBJECTIVES: We
sought to determine the most cost-effective diagnostic approach in caring for
infants in whom an initial F-Echo is concerning for CoA. METHODS: Four paradigms
for management after initial F-Echo could not rule out CoA were compared, with a
single paradigm involving additional F-Echos: (1) multiple F-Echos for diagnostic
clarity and performance of N-Echo on neonates with remaining high suspicion for
CoA on F-Echos (prenatal-multiple), (2) no further F-Echo and performance of N
Echo on neonates with high suspicion for CoA on initial F-Echo (postnatal
selective), (3) no further F-Echo and performance of N-Echo on all neonates
(postnatal-all), and (4) no further F-Echo or N-Echo with reliance on routine
physical exam to identify afflicted infants (postnatal-none). Decision analysis
models were constructed. Probabilities dictating clinical course and costs were
calculated using our institution's study population. The utility-state values
were derived from existing literature. The measure of effectiveness was quality
adjusted life years. To represent societal perspectives, cost was defined as
hospital reimbursement payments. RESULTS: From 2007 to 2014 at our institution,
92 patients were diagnosed with CoA and met the inclusion criteria for this
study. These patients presented to care either through prenatal diagnosis (n =
31), postnatal examination findings while clinically well (n = 41), or after
clinical deterioration in extremis (n = 20), with one patient subsequently dying.
Presenting in extremis was associated with a 20% increase in the cost of their
subsequent care and with a 51% increase in length of hospital stay. Postnatal
none was the least effective paradigm but also the least costly, thus forming the
baseline model. Of the three other diagnostic approaches modeled, Postnatal-all
was the cost-effective paradigm, maximizing utility due to avoidance of high
cost/low-utility disease states such as presentation in extremis and death.
Prenatal-multiple was the next most effective but was also the most expensive.
CONCLUSIONS: Echocardiography is the screening gold standard in avoiding the
devastating clinical manifestations of a missed CoA. When a diagnosis of CoA
cannot be ruled out on initial F-Echo, the most cost-effective approach is
performance of N-Echo on all neonates with no further prenatal evaluation.
PMID- 28410946
TI - Right Atrial Dysfunction in the Fetus with Severely Regurgitant Tricuspid Valve
Disease: A Potential Source of Cardiovascular Compromise.
AB - BACKGROUND: In severe right heart obstruction (RHO), redistribution of cardiac
output to the left ventricle (LV) is well tolerated by the fetal circulation.
Although the same should be true of severely regurgitant tricuspid valve disease
(rTVD) with reduced or no output from the right ventricle, affected fetuses more
frequently develop hydrops or suffer intrauterine demise. We hypothesized that
right atrium (RA) function is altered in rTVD but not in RHO, which could
contribute to differences in outcomes. METHODS: Multi-institutional retrospective
review of fetal echocardiograms performed over a 10-year period on fetuses with
rTVD (Ebstein's anomaly, tricuspid valve dysplasia) or RHO (pulmonary
atresia/intact ventricular septum, tricuspid atresia) and a healthy fetal control
group. Offline velocity vector imaging and Doppler measurements of RA size and
function and LV function were made. RESULTS: Thirty-four fetuses with rTVD, 40
with RHO, and 79 controls were compared. The rTVD fetuses had the largest RA size
and lowest RA expansion index, fractional area of change, and RA indexed filling
and emptying rates compared with fetuses with RHO and controls. The rTVD fetuses
had the shortest LV ejection time and increased Tei index with a normal LV
ejection fraction. RA dilation (odds ratio, 1.27; 95% CI, 1.05-1.54) and reduced
indexed emptying rate (odds ratio, 2.49; 95% CI, 1.07-5.81) were associated with
fetal or neonatal demise. CONCLUSIONS: Fetal rTVD is characterized by more severe
RA dilation and dysfunction compared with fetal RHO and control groups. RA
dysfunction may be an important contributor to reduced ventricular filling and
output, potentially playing a critical role in the worsened outcomes observed in
fetal rTVD.
PMID- 28410947
TI - Marching for science.
PMID- 28410948
TI - Population genetic data and mutations of 22 autosomal STR loci in Guizhou Han
population.
PMID- 28410949
TI - [Pigmentations of the oral cavity].
AB - Buccal mucosa color is explained by hemoglobin in the vessels and melanin in the
epithelium. Abnormal presence of melanin pigments (hypermelaninosis,
hypermelanocytosis), hematic pigments (hemoglobin, hemosiderin, iron) but also
some exogenous circonstancies explain pigmented lesions (figure 1). These lesions
could be localized (single lesions), multifocal (multiple lesions) or diffused.
In case of a localized pigmentation with melanic appearance, melanoma must be
systematically eliminated with a biopsy. In the case of a more diffused lesion,
systemic disease must be evoked. A drug etiology is also possible. A blood
pigment excess could be a vascular malformation (flat lesions) or a tumoral
process (nodular or swollen lesions). In both cases, Kaposi's disease should be
systematically eliminated. Pigmentations near dental restorations (amalgams,
prosthetic crowns) could be explained by an exogenous factor but a biopsy should
be performed in case of a doubt with melanoma.
PMID- 28410950
TI - Detection of Anaplasma spp. and Ehrlichia spp. anibodies, and Dirofilaria immitis
antigens in dogs from seven locations of Morocco.
AB - In Morocco no data has been published on canine exposure to Anaplasma spp.,
Borrrelia burgdorferi, and Ehrlichia spp., and only one report is available on
the occurrence of Dirofilaria immitis in dogs. Therefore, the aim of this study
was to collect current data on the canine exposure to these vector-borne
pathogens (VBPs) in Morocco. A total of 217 urban (n=57), rural (n=110) and
military (n=50) dogs from seven Moroccan locations were screened for Anaplasma
spp., B. burgdorferi and Ehrlichia spp. antibodies and for D. immitis antigens
using a commercial in-clinic ELISA test. Of these dogs, 182 (83.9%) tested
positive for at least one pathogen and positivity to two or three pathogens was
found in 14.3% and 2.3% of the dogs, respectively. Ehrlichia spp. antibodies
(34.6%) were the most frequently detected followed by Anaplasma spp. antibodies
(16.6%) and D. immitis antigens (16.1%). None of the dogs was tested seropositive
to B. burgdorferi. Statistically significant differences in seropositivity rates
were found for Ehrlichia spp. and D. immitis in rural dogs especially those from
the north central region (p<0.001) but not for Anaplasma spp. No significant
difference was found according to the health status of the dog. This study
demonstrates that Moroccan dogs are at high risk of acquiring a vector-borne
infection.
PMID- 28410951
TI - Effect of acidity on the physicochemical properties of alpha- and beta-chitin
nanofibers.
AB - We have investigated whether acidity can be used to control the physicochemical
properties of chitin nanofibers (ChNFs). In this study, we define acidity as the
molar ratio of dissociated protons from the acid to the amino groups in the raw
chitin powder. The effect of acidity on the physicochemical properties of alpha-
and beta-ChNFs was compared. The transmittance and viscosity of the beta-ChNFs
drastically and continuously increased with increasing acidity, while those of
the alpha-ChNFs were not affected by acidity. These differences are because of
the higher ability for cationization based on the more flexible crystal structure
of beta-chitin than alpha-chitin. In addition, the effect of the acid species on
the transmittance of beta-ChNFs was investigated. The transmittance of beta-ChNFs
can be expressed by the acidity regardless of the acid species, such as
hydrochloric acid, phosphoric acid, and acetic acid. These results indicate that
the acidity defined in this work is an effective parameter to define and control
the physicochemical properties of ChNFs.
PMID- 28410952
TI - Molecular cloning and functional characterization of multiple NADPH-cytochrome
P450 reductases from Andrographis paniculata.
AB - Andrographis paniculata (Burm.f.) Wall. ex Nees is widely used as medicinal herb
in Southern and Southeastern Asia and andrographolide is its main medicinal
constituent. Based on the structure of andrographolide, it has been proposed that
cytochrome P450 enzymes play vital roles on its biosynthesis. NADPH:cytochrome
P450 reductase (CPR) is the most important redox partner of multiple P450s. In
this study, three CPRs were identified in the genomic data of A. paniculata
(namely ApCPR1, ApCPR2, and ApCPR3), and their coding regions were cloned. They
varied from 62% to 70% identities to each other at the amino acid sequence level.
ApCPR1 belongs to Class I of dicotyledonous CPR while both ApCPR2 and ApCPR3 are
grouped to Class II. The recombinant enzymes ApCPR1 and ApCPR2 reduced cytochrome
c and ferricyanide in an NADPH-dependent manner. In yeast, they supported the
activity of CYP76AH1, a ferruginol-forming enzyme. However, ApCPR3 did not show
any enzymatic activities either in vitro or in vivo. Quantitative real-time PCR
analysis showed that both ApCPR1 and ApCPR2 expressed in all tissues examined,
but ApCPR2 showed higher expression in leaves. Expression of ApCPR2 was inducible
by MeJA and its pattern matched with andrographolide accumulation. Present
investigation suggested ApCPR2 involves in the biosynthesis of secondary
metabolites including andrographolide.
PMID- 28410953
TI - Spontaneous cerebrospinal fluid fistula in the clivus.
AB - INTRODUCTION: Spontaneous cerebrospinal fluid (CSF) fistulas are infrequent and
only 10 cases in the literature have been located in the clivus. We describe two
new cases of CSF fistulas in this site and review the literature. CASE REPORT:
The first patient was a 52-year-old woman referred to our centre for intermittent
rhinorrhea that had been diagnosed after an episode of meningitis. The second
case was a 69-year-old man who was visited for rhinorrhea of one-year duration;
he also developed meningitis during the preoperative study. In both cases, the
spontaneous CSF fistula was diagnosed by beta-2-transferrin testing, CT scan and
MRI. We performed an endonasal endoscopic transsphenoidal approach and used free
grafts and vascularized flaps to close the clival defect. Treatment was
successful in both cases. DISCUSSION: The physiopathology of spontaneous CSF
fistulas remains unknown. Possible explanations given to date in this location
are pulsatility of the basilar artery, repeated Valsalva maneuvers and Marfan's
disease, the two latter also related to CSF fistulas in other locations. Closure
of a CSF leak towards the nasal cavity is mandatory due to potential
complications. Our results support the endoscopic transsphenoidal approach using
free grafts and/or pediculated flaps as a good alternative to open surgery.
PMID- 28410954
TI - Fatal hidradenocarcinoma of the scalp: A case report.
PMID- 28410955
TI - Isolated avascular necrosis of the olecranon.
PMID- 28410956
TI - Nine-year outcome after anatomic stemless shoulder prosthesis: clinical and
radiologic results.
AB - BACKGROUND: Several stemless shoulder implants are available on the market, but
only a few studies have presented results with sufficient mid- to long-term
follow-up. The present study evaluated clinical and radiologic outcomes 9 years
after anatomic stemless shoulder replacement. METHODS: This is a prospective
cohort study evaluating the stemless shoulder prosthesis since 2005. Anatomic
stemless shoulder replacement using a single prosthesis was performed in 49
shoulders; 17 underwent total shoulder replacement, and 32 underwent
hemiarthroplasty. Forty-three patients were clinically and radiologically
monitored after a mean of 9 years (range, 90-127 months; follow-up rate, 88%).
The indications for shoulder replacement were primary osteoarthritis in 7
shoulders, post-traumatic in 24, instability in 7, cuff tear arthropathy in 2,
postinfectious arthritis in 1, and revision arthroplasty in 2. RESULTS: The
Constant-Murley Score improved significantly from 52% to 79% (P < .0001). The
active range of motion also increased significantly for flexion from 101 degrees
to 118 degrees (P = .022), for abduction from 79 degrees to 105 degrees (P =
.02), and for external rotation from 21 degrees to 43 degrees (P < .0001).
Radiologic evaluation revealed incomplete radiolucency in 1 patient without
clinical significance or further intervention. No revision caused by loosening or
countersinking of the humeral implant was observed. CONCLUSIONS: The 9-year
outcome after stemless shoulder replacement is comparable to that of third- and
fourth-generation standard shoulder arthroplasty.
PMID- 28410957
TI - Fetal alpha 5-reductase Val89Leu mutation is associated with late miscarriage.
AB - The present study was undertaken to determine the role of different polymorphisms
affecting the testosterone/oestrogen pathway in miscarriage. Alpha 5-reductase
(SRD5A2) rs523349 and rs9282858, cytochrome P450 aromatase (CYP19A1) rs4646,
rs10046 and rs2236722 and oestrogen receptor (ESR1) rs9340799, rs2234693 and
rs6932902 polymorphisms were selected. The case group consisted of 94 samples of
formalin-fixed and paraffin-embedded fetal tissue from a miscarriage at <=24
weeks. The control group comprised a population of 331 young healthy subjects.
Only those single nucleotide polymorphisms (SNPs) fitting the Hardy-Weinberg
equilibrium (n = 4) and euploid miscarriage samples (n = 67) were included for
downstream analysis. Interestingly, SRD5A2 rs523349 (Val89Leu) was significantly
associated with the risk of undergoing miscarriage after Bonferroni correction
(odds ratio = 11.245, P < 2.2 * 10-9). Moreover, when Mantel-Cox regression
analysis was performed, we observed that the effect was significantly constrained
to the second trimester (P = 0.024, log rank). These results are compatible with
an imbalance of testosterone/dihydrotestosterone, associated with a higher risk
of miscarriage, especially in late pregnancy.
PMID- 28410958
TI - Rapid vivid-coloured dreaming induced by cerebral radiotherapy.
PMID- 28410959
TI - The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism
of combined SSRI- antipsychotic treatment in schizophrenia.
AB - Previous studies into the mechanism of SSRI-antipsychotic synergism in our
laboratory identified unique changes in the brain, particularly in the gamma
aminobutyric acid (GABA)-A receptor and its modulators. This study examined the
role of brain derived neurotrophic factor (BDNF)-cAMP response element binding
(CREB) protein signaling pathways, including protein kinase B (AKT), glycogen
synthase kinase (GSK)-3beta and related molecules in the molecular response to
haloperidol, fluvoxamine, combined haloperidol+fluvoxamine and clozapine
treatments in rat frontal cortex, hippocampus and primary cortical neuronal
cultures. The effect of fluvoxamine augmentation on BDNF-CREB pathways in
peripheral mononuclear cells (PMC's) of medicated schizophrenia patients was also
studied. Chronic haloperidol (1mg/kg) +fluvoxamine (10mg/kg) treatment increased
TrkB receptor and BDNF expression levels, and the phosphorylation of AKT/CREB/GSK
3beta, compared to the individual drugs in rat brain. In addition,
haloperidol+fluvoxamine treatment improved cognitive functions in rats,
indicating that the molecular changes may have a role in behavioral improvement.
In primary neuronal cell cultures, pretreatment with a selective PI3K inhibitor
abolished the haloperidol+fluvoxamine-induced phosphorylation of AKT and GSK
3beta, but did not affect the upregulation of CREB phosphorylation. In the
clinic, PMC's of treated patients showed upregulation of mRNA expression and
protein levels of BDNF, CREB and AKT after addition of fluvoxamine. Analyses of
PMC genes and proteins showed significant inter-correlations and some gene
changes correlated with improvement in negative and cognitive symptoms. Our study
provides new knowledge of the molecular mechanisms of symptom amelioration in
schizophrenia and may advance development of new drugs for this disease and other
neuropsychiatric disorders.
PMID- 28410961
TI - Heroin.
PMID- 28410960
TI - A Randomized Controlled Trial of a Citywide Emergency Department Care
Coordination Program to Reduce Prescription Opioid-Related Visits: An Economic
Evaluation.
AB - BACKGROUND: Care provided in the emergency department (ED) can cost up to five
times as much as care received for comparable diagnoses in alternative settings.
Small groups of patients, many of whom suffer from an opioid use disorder, often
account for a large proportion of total ED visits. We recently conducted, and
demonstrated the effectiveness of, the first randomized controlled trial of a
citywide ED care-coordination program intending to reduce prescription-opioid
related ED visits. All EDs in the metropolitan study area were connected to a Web
based information exchange system. OBJECTIVE: The objective of this article was
to perform an economic evaluation of the 12-month trial from a third-party-payer
perspective. METHODS: We modeled the person-period monthly for the 12-month
observation period, and estimated total treatment costs and return on investment
(ROI) with regard to cost offsets, over time, for all visits where the patient
was admitted to and discharged from the ED. RESULTS: By the end of month 4, the
mean cumulative cost differential was significantly lower for intervention
relative to treatment-as-usual participants (-$1370; p = 0.03); this figure
climbed to -$3200 (p = 0.02) by the end of month 12. The ROI trended upward
throughout the observation period, but failed to reach statistical significance
by the end of month 12 (ROI = 3.39, p = 0.07). CONCLUSION: The intervention
produced significant cost offsets by the end of month 4, which continued to
accumulate throughout the trial; however, ROI was not significant. Because the
per-patient administrative costs of the program are incurred at the time of
enrollment, our results highlight the importance of future studies that are able
to follow participants for a period beyond 12 months to more accurately estimate
the program's ROI.
PMID- 28410962
TI - Determinants of neurological disease: Synthesis of systematic reviews.
AB - Systematic reviews were conducted to identify risk factors associated with the
onset and progression of 14 neurological conditions, prioritized as a component
of the National Population Health Study of Neurological Conditions. These
systematic reviews provided a basis for evaluating the weight of evidence of
evidence for risk factors for the onset and progression of the 14 individual
neurological conditions considered. A number of risk factors associated with an
increased risk of onset for more than one condition, including exposure to
pesticides (associated with an increased risk of AD, amyotrophic lateral
sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette
syndrome). Coffee and tea intake was associated with a decreased risk of onset of
both dystonia and PD. Further understanding of the etiology of priority
neurological conditions will be helpful in focusing future research initiatives
and in the development of interventions to reduce the burden associated with
neurological conditions in Canada and internationally.
PMID- 28410963
TI - Regional differences in glutathione accumulation pathways in the rat cornea:
Mapping of amino acid transporters involved in glutathione synthesis.
AB - In this study we have sought to complete the identification and localisation of
uptake pathways involved in accumulating precursor amino acids involved in GSH
synthesis in the rat cornea. To do this, we performed reverse transcription PCR
(RT-PCR) to identify the Excitatory Amino Acid Transporters (EAAT 1-5)
responsible for glutamate uptake, and glycine transporters (GLYT 1-2) at the
transcript level. Western blotting was used to verify protein expression, while
immunolabelling of sagittal sections was used to localise transporters to the
different layers of the cornea. Immunolabelling of en face sections was used to
examine the subcellular distribution of proteins in the corneal endothelium. Our
findings revealed EAAT 1-5 and GLYT 1-2 to be expressed at the transcript and
protein level in the rat cornea. Immunohistochemistry revealed all amino acid
transporters to be localised to the epithelium. In the majority of cases,
labelling was restricted to the epithelium, and labelling absent from the stroma
or endothelium. However, EAAT 4 and GLYT 2 labelling was detected in the stroma
with EAAT 4 labelling also present in the endothelium. Overall, the
identification of amino acid transporters strongly supports the existence of an
intracellular GSH synthesis pathway in the rat corneal epithelium. This suggests
that regional differences in GSH accumulation pathways exist, with direct uptake
of GSH and intracellular synthesis of GSH restricted to the endothelial and
epithelial cell layers, respectively. This information is important in the design
of targeted strategies to enhance GSH levels in specific layers of the cornea to
prevent against oxidative damage, corneal swelling and loss of corneal
transparency.
PMID- 28410964
TI - Comparison of Turbo Spin Echo and Echo Planar Imaging for intravoxel incoherent
motion and diffusion tensor imaging of the kidney at 3Tesla.
AB - Echo Planar Imaging (EPI) is most commonly applied to acquire diffusion-weighted
MR-images. EPI is able to capture an entire image in very short time, but is
prone to distortions and artifacts. In diffusion-weighted EPI of the kidney
severe distortions may occur due to intestinal gas. Turbo Spin Echo (TSE) is
robust against distortions and artifacts, but needs more time to acquire an
entire image compared to EPI. Therefore, TSE is more sensitive to motion during
the readout. In this study we compare diffusion-weighted TSE and EPI of the human
kidney with regard to intravoxel incoherent motion (IVIM) and diffusion tensor
imaging (DTI). Images were acquired with b-values between 0 and 750s/mm2 with TSE
and EPI. Distortions were observed with the EPI readout in all volunteers, while
the TSE images were virtually distortion-free. Fractional anisotropy of the
diffusion tensor was significantly lower for TSE than for EPI. All other
parameters of DTI and IVIM were comparable for TSE and EPI. Especially the main
diffusion directions yielded by TSE and EPI were similar. The results demonstrate
that TSE is a worthwhile distortion-free alternative to EPI for diffusion
weighted imaging of the kidney at 3Tesla.
PMID- 28410965
TI - Permissive role of reduced inwardly-rectifying potassium current density in the
automaticity of the guinea pig pulmonary vein myocardium.
AB - The electrophysiological properties underlying the automaticity of the guinea pig
pulmonary vein myocardium were studied. About 30% of the isolated pulmonary vein
tissue preparations showed spontaneous electrical activity, as shown by glass
microelectrode recordings from their myocardial layer. The remaining quiescent
preparations had a resting membrane potential less negative than that in the left
atria. Blockade of the acetylcholine activated potassium current (IK-ACh) by
tertiapin induced a depolarizing shift of the resting membrane potential and
automatic electrical activity in the pulmonary vein, but not in the atria. The
tertiapin-induced electrical activity, as well as the spontaneous activity, was
inhibited by the application of carbachol or by chelation of intracellular Ca2+
by BAPTA. The isolated pulmonary vein cardiomyocytes had an IK-ACh density
similar to that of the atrial cardiomyocytes, but a lower density of the inwardly
rectifying potassium current (IK1). Spontaneous Ca2+ transients were observed in
about 30% of the isolated pulmonary vein cardiomyocytes, but not in atrial
cardiomyocytes. The Ca2+ transients in the pulmonary vein cardiomyocytes were
induced by tertiapin and inhibited by carbachol. These results indicate that the
pulmonary vein cardiomyocytes have a reduced density of the inwardly-rectifying
potassium current, which plays a permissive role in their intracellular Ca2+
dependent automaticity.
PMID- 28410966
TI - Vincristine-induced peripheral neuropathic pain and expression of transient
receptor potential vanilloid 1 in rat.
AB - The clinical anti-cancer efficacy of vincristine is limited by the development of
dose-dependent peripheral neuropathy. Up-regulation of transient receptor
potential vanilloid 1 (TRPV1) is correlated with peripheral neuropathy following
anti-cancer drug treatment. To analyze the contribution of TRPV1 to the
development of vincristine-induced mechanical allodynia/hyperalgesia, TRPV1
expression in the rat dorsal root ganglion (DRG) was analyzed after vincristine
treatment. Mechanical allodynia/hyperalgesia was tested with von Frey filaments
14 days after intraperitoneal administration of 0.1 mg/kg vincristine in rats.
TRPV1 expression in DRGs following vincristine treatment was assessed with
western blot analysis and in situ hybridization histochemistry. Vincristine
induced mechanical allodynia/hyperalgesia after day 14 was significantly
inhibited by the TRP antagonist ruthenium red (3 mg/kg, s.c.) and the TRPV1
antagonist capsazepine (30 mg/kg, s.c.). Vincristine treatment increased the
expression of TRPV1 protein in DRG neurons. In situ hybridization histochemistry
revealed that most of the TRPV1 mRNA-labeled neurons in the DRG were small in
size. Immunohistochemistry showed that isolectin B4-positive small DRG neurons co
expressed TRPV1 protein 14 days after treatment. These results suggest that
vincristine treatment increases TRPV1 expression in small DRG neurons. TRPV1
expression may contribute to the development of vincristine-induced painful
peripheral neuropathy.
PMID- 28410967
TI - Involvement of alpha- and beta-adrenoceptors in the automaticity of the isolated
guinea pig pulmonary vein myocardium.
AB - We examined the involvement of adrenoceptors in the automaticity of the pulmonary
vein myocardium, which probably plays a crucial role in the generation of atrial
fibrillation. The automatic activity of the myocardium in guinea pig pulmonary
vein tissue preparations were monitored by contractile force or membrane
potential measurement. In quiescent preparations, application of noradrenaline
induced an automatic activity. The firing frequency was reduced by prazosin or
atenolol. Methoxamine induced an automatic activity of low frequency, which was
accelerated by further application of isoproterenol. In preparations driven at a
constant frequency, noradrenaline, in the presence of atenolol, caused a
depolarizing shift of the resting membrane potential and an increase in the slope
of the diastolic depolarization. In contrast, in the presence of prazosin,
noradrenaline had no effect on the slope, but caused acceleration of the late
repolarization and a hyperpolarizing shift of the maximum diastolic potential. At
clinically relevant concentrations, carvedilol significantly inhibited the
noradrenaline-induced activity but bisoprolol did not. It was concluded that
alpha1- and beta1-adrenoceptor stimulation enhance automaticity through different
mechanisms in the guinea pig pulmonary vein myocardium. Dual blockade of these
adrenoceptors appears to be effective for suppressing noradrenaline-induced
pulmonary vein automaticity and probably atrial fibrillation.
PMID- 28410968
TI - Increase in serum noradrenaline concentration by short dives with bradycardia in
Indo-Pacific bottlenose dolphin Tursiops aduncus.
AB - In cetaceans, diving behavior immediately induces a change in blood circulation
to favor flow to the brain and heart; this is achieved by intense
vasoconstriction of the blood vessels that serve other organs. This blood
circulation response is allied to a decrease in heart rate in order to optimize
oxygen usage during diving. Vasoconstrictors are present in all mammals and
stimulate the contraction of the smooth muscle in the walls of blood vessels. The
most important of these vasoconstrictors are the hormones adrenaline (A),
noradrenaline (NA), and angiotensin II (ANG II). At present, the contribution of
these hormones to vasoconstriction during diving in cetaceans is unclear. To
elucidate their possible roles, changes in serum levels of A, NA and ANG II were
monitored together with heart rate in the Indo-Pacific bottlenose dolphin
Tursiops aduncus during 90 and 180s dives. Both brief diving periods induced an
increase in serum NA concentration and a decrease in heart rate; however, no
changes were detected in serum levels of A or ANG II. These data indicate that NA
may play a role in diving-induced vasoconstriction.
PMID- 28410969
TI - Characterization and mechanism of phosphoinositide 3-kinases (PI3Ks) members in
insulin-induced changes of protein metabolism in yellow catfish Pelteobagrus
fulvidraco.
AB - In the present study, seven phosphoinositide 3-kinase (PI3K) members (PI3KCa,
PI3KCb, PI3KCd, PI3KCg, PI3KC2a, PI3KC2b and PI3KC3, respectively) were isolated
and characterized from yellow catfish Pelteobagrus fulvidraco, and their roles in
insulin-induced changes of protein metabolism were determined. These seven PI3Ks
can be divided into three classes, class I (including PI3KCa, PI3KCb, PI3KCd and
PI3KCg), class II (including PI3KC2a and PI3KC2b) and class III (only including
PI3KC3). Compared with mammals, all of these members share similar domain
structure. Their mRNAs were widely expressed across ten tested tissues (liver,
white muscle, spleen, brain, gill, mesenteric fat, intestine, heart, kidney and
ovary), but at variable levels. In the in vivo study, insulin treatment
significantly increased hepatic protein content at 3h, accompanied with reduced
plasma total amino acid contents and liver ALT activity, and with increased total
RNA content and the mRNA levels of PI3KCb, PI3KC2a, AKT2, mTORC1 and S6K1 in
liver. At 6h and 12h, insulin injection showed no significant effect on liver
protein content and plasma total amino acid, but reduced liver ALT activity and
increased liver total RNA and the mRNA levels of AKT2, mTORC1 and S6K1 in liver
at 6h. In the in vitro study, insulin incubation also tended to increase protein
content of hepatocytes, accompanied with reduced cell medium total amino acid
contents and hepatocytes ALT activity, and increased total RNA content and the
mRNA levels of PI3KCb, PI3KC2a, AKT2, mTORC1 and S6K1 in hepatocytes. However,
insulin treatment showed no significant effect on GDH activity and mRNA
expression of PI3KCa, PI3KCd, PI3KCg, PI3KC2b, PI3KC3 and eEF2 both in the in
vivo and in vitro studies. Effects of insulin on the mRNA levels of eIF-4E and 4E
BP1 were different between the in vivo and in vitro studies, and also time
dependent. Compared to single insulin group, insulin+wortmannin group increased
ALT activity at 6h but reduced T-RNA content at 6 and 12h. AKT2 and S6K1 mRNA
levels at 6 and 12h, mRNA levels of mTORC1, 4E-BP1 and eEF2 at 3 and 6h, and EIF
4E mRNA levels at 3 and 12h, PI3KCb and PI3KC2a mRNA levels were significantly
lower in insulin+wortmannin group than those in single insulin group. Thus, our
study demonstrated that among seven PI3K members, PI3KCb and PI3KC2a were more
sensitive to the insulin signaling pathway, and insulin stimulated hepatic
protein synthesis in yellow catfish through PI3K signaling pathway.
PMID- 28410970
TI - Insulin and insulin-like growth factor-1 modulate the lipolytic action of growth
hormone by altering signal pathway linkages.
AB - Growth hormone (GH) has many actions in vertebrates, including the regulation of
two disparate metabolic processes: growth promotion (anabolic) and the
mobilization of stored lipids (catabolic). Our previous studies showed that GH
stimulated IGF-1 production in hepatocytes from fed rainbow trout, but in cells
from fasted fish GH stimulated lipolysis. In this study, we used rainbow trout
(Oncorhynchus mykiss) to elucidate regulation of the mechanisms that enable cells
to alter their lipolytic responsiveness to GH. In the first experiment, cells
were removed from either fed or fasted fish, conditioned in medium containing
serum (10%) from either fed or fasted fish, then challenged with GH. GH
stimulated the expression of hormone sensitive lipase (HSL), the primary
lipolytic enzyme, in cells from fasted fish conditioned with "fasted serum" but
not in cells from fasted fish conditioned in "fed serum." Pretreatment of cells
from fed fish with "fasted serum" resulted in GH-stimulated HSL expression,
whereas GH-stimulated HSL expression in cells from fasted fish was blocked by
conditioning in "fed serum." The nature of the conditioning serum governed the
signaling pathways activated by GH irrespective of the nutritional state of the
animals from which the cells were removed. When hepatocytes were pretreated with
"fed serum," GH activated JAK2, STAT5, Akt, and ERK pathways; when cells were
pretreated with "fasted serum," GH activated PKC and ERK. In the second study, we
examined the direct effects of insulin (INS) and insulin-like growth factor (IGF
1), two nutritionally-regulated hormones, on GH-stimulated lipolysis and signal
transduction in isolated hepatocytes. GH only stimulated HSL mRNA expression in
cells from fasted fish. Pretreatment with INS and/or IGF-1 abolished this
lipolytic response to GH. INS and/or IGF-1 augmented GH activation of JAK2 and
STAT5 in cells from fed and fasted fish. However, INS and/or IGF-1 eliminated the
ability of GH to activate PKC and ERK from fasted cells. These results indicate
that INS and IGF-1 determine the signaling pathways activated by GH and whether
or not a lipolytic response ensues. Such hormone-receptor-signal pathway linkages
provide insight into the molecular basis of GH multifunctionality and into how
cellular responses to GH can be adjusted to meet physiological (e.g.,
nutritional), developmental, or other conditions.
PMID- 28410972
TI - Fostering Resilience among Mothers under Stress: "Authentic Connections Groups"
for Medical Professionals.
AB - BACKGROUND: We report on effects of an intervention to foster resilience among
professional women at high risk for stress and burnout: health care providers
(physicians, PhD clinicians, physician assistants, and nurse practitioners) who
are mothers. METHODS: Between February and November 2015, 40 mothers on staff at
the Mayo Clinic, Arizona, were assigned randomly to either 1) 12 weekly 1-hour
sessions of a structured, relational supportive intervention, the Authentic
Connections Groups (n = 21) with protected time to attend sessions or to 2) 12
weekly hours of protected time to be used as desired (controls; n = 19).
Participants were assessed at baseline, after the intervention, and 3 months
follow-up on multiple psychological measures plus plasma cortisol. RESULTS:
Across the 12 weeks of the intervention groups, there were zero dropouts. After
the intervention, analyses of covariance showed significantly greater
improvements (p < .05) for mothers in the Authentic Connections Groups than
control condition for depression and global symptoms. By 3 months follow-up,
significant differences were seen for these two dimensions and almost all other
central variables, including self-compassion, feeling loved, physical affection
received, and parenting stress, with moderate effect sizes (etap2 0.08-0.19;
median, 0.16). Participants in the Authentic Connections Groups (but not control)
condition also showed significant reductions in cortisol levels at both after the
intervention and follow-up. CONCLUSIONS: Facilitated colleague support groups
could be a viable, low-cost, preventive intervention to mitigate burnout and
distress for mothers in high-stress professional settings such as hospitals,
resulting in personal benefit, greater engagement at work, and attenuated stress
associated with parenting.
PMID- 28410971
TI - The Association between Parity and Inflammation among Mexican-American Women of
Reproductive Age Varies by Acculturation Level: Results of the National Health
and Nutrition Examination Survey (1999-2006).
AB - INTRODUCTION: Parity and acculturation are linked with cardiometabolic risk.
Their joint association with cardiometabolic health among Mexican-American women
is less established, even though immigrant Mexican-American women have the
highest fertility rate in the United States. We examined the modifying role of
acculturation on the association of parity with a cardiometabolic risk biomarker,
C-reactive protein (CRP). METHODS: Participants (n = 1,002) were women of Mexican
background, ages 16 to 39 years, in the National Health and Nutrition Examination
Survey (NHANES) from 1999 through 2006. The association between parity and
elevated CRP was examined using logistic regression adjusted for age, household
food security, access to health care, hemoglobin A1c, total cholesterol, high
density lipoprotein cholesterol, waist circumference, physical activity,
acculturation, and a product term of parity and acculturation. Acculturation was
measured on a 6-point score based on nativity status and duration of residence in
the United States (0, Mexico born, U.S. resident <10 years; 1, Mexico born, U.S.
resident 10-19 years; 2-Mexico born, U.S. resident >=20 years; and 3, U.S. born),
and language used at home (0, Spanish; 1, bilingual; 2, English). Scores of 0 or
1, 2 or 3, and 4 or 5 represented low, moderate, and high acculturation,
respectively. RESULTS: The association of parity with elevated CRP varied by
acculturation level (pinteraction = 0.10). Parity was associated with elevated
CRP among women with low (adjusted odds ratio [OR], 2.26; 95% CI, 1.07-4.80) and
moderate acculturation (adjusted OR, 2.79; 95% CI, 1.16-6.73), compared with
nulliparous women. CONCLUSIONS: Higher odds of elevated CRP associated with
parity in immigrant Mexican-American women of reproductive age indicate the need
for greater use of maternal/women's health care services for cardiometabolic risk
screening and interventions.
PMID- 28410973
TI - The Influence of Relationship Power and Partner Communication on the Syndemic
Factor among Hispanic Women.
AB - BACKGROUND: This study expands research on the substance abuse, intimate partner
violence, human immunodeficiency virus (HIV), and depression syndemic theory for
Hispanic women. We hypothesized relationship power and partner communication
would be related to the syndemic. METHODS: Data were used from the baseline
assessment of an effectiveness trial of SEPA (Salud/Health, Educacion/Education,
Prevencion/Prevention, and Autocuidado/Self-care), an HIV/sexually transmitted
infection risk reduction program for Hispanic women. Hispanic adult women (n =
320) completed measures (in Spanish or English) of relationship power, partner
communication about HIV, and acculturation. The syndemic was defined with a
factor model of substance abuse, intimate partner violence, risk for HIV/sexually
transmitted infection, and depression using structural equation modeling.
RESULTS: Controlling for acculturation and education, relationship power was
inversely related to the syndemic factor (beta = -0.49, p < .001), but partner
communication was not (beta = 0.14, p = .054). Acculturation and education were
also related to the syndemic factor. These variables combined accounted for more
than one-half (53%) of the variance in the syndemic factor. CONCLUSIONS: Findings
suggest the need to develop and test interventions that address the power
dynamics of intimate relationships as a means of reducing health disparities
among Hispanic women.
PMID- 28410974
TI - Short Interpregnancy Intervals: Results from the First Baby Study.
AB - BACKGROUND: Short interpregnancy interval (SIPI), defined as 18 months or fewer
between delivery and subsequent conception, has become an independent marker of
maternal and child health. METHODS: We performed a secondary analysis of 18
months of data from The First Baby Study, a prospective cohort of women followed
from pregnancy through 3 years after their first birth. Women with SIPIs by 6, 6
to 12, and 12 to 18 months were compared with those without conceptions at those
times. We then analyzed pregnancy intention of the subpopulation of women with a
SIPI of 18 months or fewer. Logistic regression analyses determined associations
between maternal characteristics, including sociodemographic and reproductive
indicators, and SIPI incidence and intention. FINDINGS: Of 3,006 participants,
795 (26.5%) had a repeat pregnancy within 18 months: 58 (1.9%) occurred within 6
months, 242 (8.1%) between 6 and 12 months, and 495 (16.5%) between 12 and 18
months. Incidence of SIPI at each interval differed by maternal characteristics,
including income, marital status, and intention. Most women (84%) with a SIPI of
6 months or less classified them as unintended. Less than 2% of women with SIPIs
of 18 months or fewer reported any contraceptive use in the postpartum period and
no pregnancies occurred with the use of very effective methods, including long
acting reversible contraception. CONCLUSIONS: The population of women at risk for
SIPI is not homogenous. Among those with SIPIs, there is a stark contrast in
intention between those who conceive early (<=6 months) versus later (>=12
months). Given that almost no pregnancies occurred when women used postpartum
contraception, contraceptive counseling and unfettered access should be available
for those at greatest risk for an early, repeat, unintended pregnancy.
PMID- 28410975
TI - Engagement of nurses in their profession. Qualitative study on engagement.
AB - OBJECTIVE: To identify common issues of nurses with high engagement to enable us
to develop the construct as it applies to nursing in more depth. METHOD: Based on
the constructivist paradigm and with a phenomenological approach, a qualitative
content analysis was conducted using an inductive approach. Participants were
nurses working in direct care in different healthcare areas. The sample size was
determined by data saturation and 15 participants were interviewed. RESULTS: The
units of meaning were grouped into 11 subcategories, and then into 7 categories
termed vigour, dedication, reward, autonomy, social support, conciliation and
attributes of nurses. Then these categories were grouped into 3 major themes: job
characteristics, characteristics of organizations, and individual
characteristics. CONCLUSIONS: Having high engagement does not mean ignoring the
negative aspects of work and organizations. Nurses who maintain high engagement
are also affected by the negative aspects, however the assessment of positive
aspects such as enjoying the work, the meaning of being a nurse, reward and
autonomy enable the process of depletion of engagement to be overcome. In view of
the findings, we propose reconceptualising the construct, taking the features of
nursing into account.
PMID- 28410976
TI - Genome editing via delivery of Cas9 ribonucleoprotein.
AB - The CRISPR-Cas genome editing system is very powerful. The format of the CRISPR
reagents and the means of delivery are often important factors in targeting
efficiency. Delivery of recombinant Cas9 protein and guide RNA (gRNA) as a
preformed ribonucleoprotein (RNP) complex has recently emerged as a powerful and
general approach to genome editing. Here we outline methods to produce and
deliver Cas9 RNPs. A donor DNA carrying desired sequence changes can also be
included to program precise sequence introduction or replacement. RNP delivery
limits exposure to genome editing reagents, reduces off-target events, drives
high rates of homology-dependent repair, and can be applied to embryos to rapidly
generate animal models. RNP delivery thus minimizes some of the pitfalls of
alternative editing modalities and is rapidly being adopted by the genome editing
community.
PMID- 28410977
TI - Intravital imaging of the kidney.
AB - Two-photon intravital microscopy is a powerful tool that allows the examination
of dynamic cellular processes in the live animal with unprecedented resolution.
Indeed, it offers the ability to address unique biological questions that may not
be solved by other means. While two-photon intravital microscopy has been
successfully applied to study many organs, the kidney presents its own unique
challenges that need to be overcome in order to optimize and validate imaging
data. For kidney imaging, the complexity of renal architecture and salient
autofluorescence merit special considerations as these elements directly impact
image acquisition and data interpretation. Here, using illustrative cases, we
provide practical guides and discuss issues that may arise during two-photon live
imaging of the rodent kidney.
PMID- 28410978
TI - Performance monitoring in nicotine dependence: Considering integration of recent
reinforcement history.
AB - INTRODUCTION: Impaired monitoring of errors and conflict (performance monitoring;
PM) is well documented in substance dependence (SD) including nicotine dependence
and may contribute to continued drug use. Contemporary models of PM and
complementary behavioural evidence suggest that PM works by integrating recent
reinforcement history rather than evaluating individual behaviours. Despite this,
studies of PM in SD have typically used indices derived from reaction to task
error or conflict on individual trials. Consequently impaired integration of
reinforcement history during action selection tasks requiring behavioural control
in SD populations has been underexplored. METHODS: A reinforcement learning task
assessed the ability of abstinent, satiated, former and never smokers (N=60) to
integrate recent reinforcement history alongside a more typical behavioural index
of PM reflecting the degree of reaction time slowing following an error (post
punishment slowing; PPS). RESULTS: On both indices there was a consistent pattern
in PM data: Former smokers had the greatest and satiated smokers the poorest PM.
Specifically satiated smokers had poorer reinforcement integration than former
(p=0.005) and never smokers (p=0.041) and had less post-punishment slowing than
former (p<0.001), never (p=0.003) and abstinent smokers (p=0.026). CONCLUSIONS:
These are the first data examining the effects of smoking status on PM that use
an integration of reinforcement history metric. The concordance of the
reinforcement integration and PPS data suggest that this could be a promising
method to interrogate PM in future studies. PM is influenced by smoking status.
As PM is associated with adapting behaviour, poor PM in satiated smokers may
contribute towards continued smoking despite negative consequences. Former
smokers show elevated PM suggesting this may be a good relapse prevention target
for individuals struggling to remain abstinent however prospective and
intervention studies are needed. A better understanding of PM deficits in terms
of reinforcement integration failure may stimulate development of novel treatment
approaches.
PMID- 28410979
TI - Post-migration follow-up of migrants identified to be at increased risk of
developing tuberculosis at pre-migration screening: a systematic review and meta
analysis.
AB - BACKGROUND: Post-migration follow-up of migrants considered at increased risk of
developing tuberculosis based on pre-migration screening abnormalities (high-risk
migrants) is implemented in several low-incidence countries. We aimed to
determine the rate of tuberculosis in this population to inform cross-border
tuberculosis control policies. METHODS: We searched MEDLINE and Embase (since
inception to Jan 12, 2017) for studies evaluating post-migration follow-up of
high-risk migrants. Outcomes evaluated were the number of tuberculosis cases
occurring post-migration, expressed as the tuberculosis incidence per 100 000
person-years of follow-up, as cumulative incidence of tuberculosis per 100 000
persons, and the cumulative incidence of tuberculosis at the first post-migration
follow-up visit. Random-effects models were used to summarise outcomes across
studies. FINDINGS: We identified 20 publications (describing 23 study cohorts)
reporting the pre-migration screening outcomes of 8 355 030 migrants processed
between Jan 1, 1981, and May 1, 2014, with 222 375 high-risk migrants identified.
The pooled cumulative incidence of tuberculosis post-migration in our study
population from 22 cohorts was 2794 per 100 000 persons (95% CI 2179-3409;
I2=99%). The pooled cumulative incidence of tuberculosis at the first follow-up
visit from ten cohorts was 3284 per 100 000 persons (95% CI 2173-4395; I2=99%).
The pooled tuberculosis incidence from 15 cohorts was 1249 per 100 000 person
years of follow-up (95% CI 924-1574; I2=98%). INTERPRETATION: The high rate of
tuberculosis in high-risk migrants suggests that tuberculosis control measures in
this population, including more sensitive pre-migration screening, preventive
treatment of latent tuberculosis infection, or post-migration follow-up, are
potentially effective cross-border tuberculosis control strategies in low
incidence countries. FUNDING: Australian National Health and Medical Research
Council.
PMID- 28410980
TI - Effectiveness of post-migration tuberculosis screening.
PMID- 28410981
TI - Predicting healthcare trajectories from medical records: A deep learning
approach.
AB - Personalized predictive medicine necessitates the modeling of patient illness and
care processes, which inherently have long-term temporal dependencies. Healthcare
observations, stored in electronic medical records are episodic and irregular in
time. We introduce DeepCare, an end-to-end deep dynamic neural network that reads
medical records, stores previous illness history, infers current illness states
and predicts future medical outcomes. At the data level, DeepCare represents care
episodes as vectors and models patient health state trajectories by the memory of
historical records. Built on Long Short-Term Memory (LSTM), DeepCare introduces
methods to handle irregularly timed events by moderating the forgetting and
consolidation of memory. DeepCare also explicitly models medical interventions
that change the course of illness and shape future medical risk. Moving up to the
health state level, historical and present health states are then aggregated
through multiscale temporal pooling, before passing through a neural network that
estimates future outcomes. We demonstrate the efficacy of DeepCare for disease
progression modeling, intervention recommendation, and future risk prediction. On
two important cohorts with heavy social and economic burden - diabetes and mental
health - the results show improved prediction accuracy.
PMID- 28410982
TI - EHR-based phenotyping: Bulk learning and evaluation.
AB - In data-driven phenotyping, a core computational task is to identify medical
concepts and their variations from sources of electronic health records (EHR) to
stratify phenotypic cohorts. A conventional analytic framework for phenotyping
largely uses a manual knowledge engineering approach or a supervised learning
approach where clinical cases are represented by variables encompassing
diagnoses, medicinal treatments and laboratory tests, among others. In such a
framework, tasks associated with feature engineering and data annotation remain a
tedious and expensive exercise, resulting in poor scalability. In addition,
certain clinical conditions, such as those that are rare and acute in nature, may
never accumulate sufficient data over time, which poses a challenge to
establishing accurate and informative statistical models. In this paper, we use
infectious diseases as the domain of study to demonstrate a hierarchical learning
method based on ensemble learning that attempts to address these issues through
feature abstraction. We use a sparse annotation set to train and evaluate many
phenotypes at once, which we call bulk learning. In this batch-phenotyping
framework, disease cohort definitions can be learned from within the abstract
feature space established by using multiple diseases as a substrate and
diagnostic codes as surrogates. In particular, using surrogate labels for model
training renders possible its subsequent evaluation using only a sparse annotated
sample. Moreover, statistical models can be trained and evaluated, using the same
sparse annotation, from within the abstract feature space of low dimensionality
that encapsulates the shared clinical traits of these target diseases,
collectively referred to as the bulk learning set.
PMID- 28410983
TI - Toward better public health reporting using existing off the shelf approaches:
The value of medical dictionaries in automated cancer detection using plaintext
medical data.
AB - OBJECTIVES: Existing approaches to derive decision models from plaintext clinical
data frequently depend on medical dictionaries as the sources of potential
features. Prior research suggests that decision models developed using non
dictionary based feature sourcing approaches and "off the shelf" tools could
predict cancer with performance metrics between 80% and 90%. We sought to compare
non-dictionary based models to models built using features derived from medical
dictionaries. MATERIALS AND METHODS: We evaluated the detection of cancer cases
from free text pathology reports using decision models built with combinations of
dictionary or non-dictionary based feature sourcing approaches, 4 feature subset
sizes, and 5 classification algorithms. Each decision model was evaluated using
the following performance metrics: sensitivity, specificity, accuracy, positive
predictive value, and area under the receiver operating characteristics (ROC)
curve. RESULTS: Decision models parameterized using dictionary and non-dictionary
feature sourcing approaches produced performance metrics between 70 and 90%. The
source of features and feature subset size had no impact on the performance of a
decision model. CONCLUSION: Our study suggests there is little value in
leveraging medical dictionaries for extracting features for decision model
building. Decision models built using features extracted from the plaintext
reports themselves achieve comparable results to those built using medical
dictionaries. Overall, this suggests that existing "off the shelf" approaches can
be leveraged to perform accurate cancer detection using less complex Named Entity
Recognition (NER) based feature extraction, automated feature selection and
modeling approaches.
PMID- 28410984
TI - A systematic review of complications associated with direct implants vs. tissue
expanders following Wise pattern skin-sparing mastectomy.
AB - INTRODUCTION: With proven oncological safety and improved aesthetic outcomes, the
Type IV or "Wise pattern" skin-sparing mastectomy (SSM) is a procedure that is
being performed with increasing frequency. Unfortunately, it is also associated
with an increased risk of complications. The purpose of this investigation was to
determine the complications associated with direct-to-implant and two-step tissue
expander breast reconstruction following Wise pattern SSM. METHODS: Systematic
electronic searches were performed using PubMed, MEDLINE, and Embase databases.
Search terms used were those for studies reporting complications following breast
reconstruction using direct-to-implant and two-step tissue-expander approaches
following Wise pattern SSM. Included studies were graded for their risk of bias.
Pooled descriptive statistics on overall complication rates, skin flap necrosis,
delayed wound healing, hematoma, and infections were performed for both
procedures. Other complications specific to each procedure were also reported.
RESULTS: A total of 16 articles met the inclusion criteria for this
investigation, representing 561 direct-to-implant or two-step breast
reconstruction procedures. For direct-to-implant reconstructions, the pooled
complication rate was 30%, while for those using tissue expansion, it was 20.3%.
Rates of skin flap necrosis (9.70%, 4.69%), delayed wound healing (2.77%, 0.78%),
infection (2.54%, 3.91%), seroma (1.15%, 4.68%), and hematoma (0.92%, 0.78%) were
calculated for direct-to-implant procedures and two-step tissue expansion,
respectively. CONCLUSION: Following Wise pattern SSM, direct-to-implant
reconstruction appears to be associated with an increased rate of overall
complications and skin flap necrosis. Modification of the procedure through the
placement of a de-epithelialized dermal flap may help limit delays in wound
healing and infection. Future investigations that report complication rates for
SSM should present data that are segregated according to the type of procedure
and the method of reconstruction.
PMID- 28410985
TI - Rectus femoris muscle necrosis: An underrated donor-site complication of free
anterolateral thigh flap.
PMID- 28410986
TI - Predictors of biochemical recurrence after primary focal cryosurgery
(hemiablation) for localized prostate cancer: A multi-institutional analytic
comparison of Phoenix and Stuttgart criteria.
AB - BACKGROUND: The Phoenix definition (PD) and Stuttgart definition (SD) designed to
determine biochemical recurrence (BCR) in patients with postradiotherapy and high
intensity focused ultrasound organ-confined prostate cancer are being applied to
follow patients after cryosurgery. We sought to identify predictors of BCR using
the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC).
MATERIALS AND METHODS: We performed a retrospective review of patients who
underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients
were followed up with serial prostate-specific antigen (PSA). PSA levels, pre-
and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA
nadir+2ng/ml]; SD = [PSA nadir+1.2ng/ml]) were recorded. Patients who experienced
BCR were biopsied, monitored carefully or treated at the discretion of the
treating urologist. Cox regression and survival analyses were performed to assess
time to BCR using PD and SD. RESULTS: A total of 163 patients were included with
a median follow-up of 36.6 (interquartile range: 18.9-56.4) months. In all, 64
(39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On
multivariable Cox regression, the number of positive pre-PFC biopsy cores was an
independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR
= 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR
using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival
analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and
SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and
18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those
with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and
66.7% of those with BCR by the SD were found to have a Gleason score >=7.
CONCLUSION: Both the PD and the SD may be used to determine BCR in post-PFC
patients. However, the ideal definition of BCR after PFC remains to be
elucidated.
PMID- 28410987
TI - Alkaline phosphatase velocity predicts overall survival and bone metastasis in
patients with castration-resistant prostate cancer.
AB - INTRODUCTION AND OBJECTIVES: Identifying patients with prostate cancer (CaP) who
will ultimately develop bone metastasis (BM) or die of disease is essential.
Alkaline phosphatase velocity (APV) has been shown to predict overall survival
(OS) and bone metastasis-free survival (BMFS) in an earlier study of an equal
access military patient cohort of patients with castrate-resistant prostate
cancer (CRPC). To confirm these findings, we examined a cohort of patients from a
high-volume cancer center to validate a previous observation that faster alkaline
phosphatase (AP) kinetics are predictive of OS and BMFS in this second cohort of
patients. MATERIALS AND METHODS: A retrospective cohort study was conducted of
patients with CRPC treated at Memorial Sloan Kettering Cancer Center between 1989
and 2010. All patients who received androgen deprivation therapy (ADT) as primary
treatment in response to a rising PSA after definitive surgery for CaP were
eligible. For those who received primary ADT or surgery followed by ADT, CRPC was
defined as one rising PSA value after a PSA nadir <=4ng/ml, and confirmed by a
second rising PSA value, with concurrently documented testosterone levels
<50ng/dl. APV was computed as the slope of the linear regression line of all AP
values (>2 values per patient) plotted against time. Study outcome included BMFS
and OS. Univariable Kaplan-Meier analysis was used to examine time-to-event
outcomes. Multivariable Cox proportional hazards regression analysis was used to
model time to BMFS and OS. RESULTS: Of 89 patients with CRPC with evaluable data
and CRPC, 17 (19%) experienced BM and 26 (29%) died. APV was dichotomized at the
uppermost quartile split of all observed APV values:>=5.42U/l/y vs. the lower 3
quartiles combined,<5.42U/l/y. Patients with faster APV had significantly worse
outcomes, including faster progression to BM and poorer OS when compared with
those with slower APV (P = 0.0451 and P = 0.0109, respectively). There was strong
correlation between PSA doubling time (PSADT) (<10,>=10mo) and APV (>=5.42U/l/y
vs.<5.42U/l/y) (P = 0.0289), preventing simultaneous evaluation of both factors
in multivariable analysis. Kaplan-Meier analysis showed that PSADT was also
predictive of BM and OS (log-rank P<0.0001). Separate multivariable Cox
proportional hazards regression models were used to examine PSADT and APV, as
predictors of each study outcome (BMFS and OS). Both PSADT and APV were strongly
predictive of BMFS and OS (respectively). CONCLUSIONS: APV and PSADT were
predictors of BM and OS in patients with CRPC, respectively. These data are
additional evidence of the potential value of AP kinetics in patients with
advanced CaP. Prospective studies will be required to clarify these associations.
However, given the restrictions on the current patient population in excluding
metastatic disease within 12 months of ADT and a PSA nadir >4ng/ml, the findings
are not inappropriately generalized to other men.
PMID- 28410989
TI - Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8+
T Cell Terminal Differentiation and Loss of Multipotency.
AB - Understanding immunological memory formation depends on elucidating how
multipotent memory precursor (MP) cells maintain developmental plasticity and
longevity to provide long-term immunity while other effector cells develop into
terminally differentiated effector (TE) cells with limited survival. Profiling
active (H3K27ac) and repressed (H3K27me3) chromatin in naive, MP, and TE CD8+ T
cells during viral infection revealed increased H3K27me3 deposition at numerous
pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate
restriction, but permissive chromatin at both pro-memory and pro-effector genes
in MP cells, indicative of multipotency. Polycomb repressive complex 2 deficiency
impaired clonal expansion and TE cell differentiation, but minimally impacted
CD8+ memory T cell maturation. Abundant H3K27me3 deposition at pro-memory genes
occurred late during TE cell development, probably from diminished transcription
factor FOXO1 expression. These results outline a temporal model for loss of
memory cell potential through selective epigenetic silencing of pro-memory genes
in effector T cells.
PMID- 28410990
TI - Tyrosine Kinase SYK Licenses MyD88 Adaptor Protein to Instigate IL-1alpha
Mediated Inflammatory Disease.
AB - Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6spin mice)
develop an inflammatory skin disease that resembles neutrophilic dermatosis in
humans. Here, we demonstrated that interleukin-1alpha (IL-1alpha) signaling
through IL-1R and MyD88 in both stromal and immune cells drive inflammation in
Ptpn6spin mice. We further identified SYK as a critical kinase that
phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis
in Ptpn6spin mice. Our studies further demonstrated that SHP1 encoded by Ptpn6
binds and suppresses SYK activation to inhibit MyD88 phosphorylation. Downstream
of SHP1 and SYK-dependent counterregulation of MyD88 tyrosine phosphorylation, we
have demonstrated that the scaffolding function of receptor interacting protein
kinase 1 (RIPK1) and tumor growth factor-beta activated kinase 1 (TAK1)-mediating
signaling were required to spur inflammatory disease. Overall, these studies
identify SHP1 and SYK crosstalk as a critical regulator of MyD88 post
translational modifications and IL-1-driven inflammation.
PMID- 28410992
TI - Ethical issues in education: Medical trainees and the global health experience.
AB - With interest in global health experiences (GHEs) by medical trainees remaining
high, the number of global health programs offering educational experiences in
resource limited settings has proliferated. Development and implementation of
GHEs has outpaced the critical evaluation of ethical considerations inherent in
these programs. Global health programs must adhere to the four principles of
beneficence, nonmaleficence, respect of autonomy, and justice in crafting a GHE
focused on maximizing the experience of the learners, host country, and patients.
The four ethical principles provide a guideline for the development and
implementation of highly ethical GHEs for medical trainees.
PMID- 28410988
TI - Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and
Synergizes with PD-1 Blockade to Eradicate Established Tumors.
AB - CD25 is expressed at high levels on regulatory T (Treg) cells and was initially
proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have
displayed limited activity against established tumors. We demonstrated that CD25
expression is largely restricted to tumor-infiltrating Treg cells in mice and
humans. While existing anti-CD25 antibodies were observed to deplete Treg cells
in the periphery, upregulation of the inhibitory Fc gamma receptor (FcgammaR) IIb
at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie
the lack of anti-tumor activity previously observed in pre-clinical models. Use
of an anti-CD25 antibody with enhanced binding to activating FcgammaRs led to
effective depletion of tumor-infiltrating Treg cells, increased effector to Treg
cell ratios, and improved control of established tumors. Combination with anti
programmed cell death protein-1 antibodies promoted complete tumor rejection,
demonstrating the relevance of CD25 as a therapeutic target and promising
substrate for future combination approaches in immune-oncology.
PMID- 28410991
TI - NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with
Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8.
AB - Intestinal epithelial cells (IECs) form a critical barrier against pathogen
invasion. By generation of mice in which inflammasome expression is restricted to
IECs, we describe a coordinated epithelium-intrinsic inflammasome response in
vivo. This response was sufficient to protect against Salmonella tissue invasion
and involved a previously reported IEC expulsion that was coordinated with lipid
mediator and cytokine production and lytic IEC death. Excessive inflammasome
activation in IECs was sufficient to result in diarrhea and pathology.
Experiments with IEC organoids demonstrated that IEC expulsion did not require
other cell types. IEC expulsion was accompanied by a major actin rearrangement in
neighboring cells that maintained epithelium integrity but did not absolutely
require Caspase-1 or Gasdermin D. Analysis of Casp1-/-Casp8-/- mice revealed a
functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic,
Caspase-1 and -8 inflammasome response plays a key role in intestinal immune
defense and pathology.
PMID- 28410993
TI - Development of a novel recombinant LHRH fusion protein for therapy of androgen
and estrogen dependent cancers.
AB - LHRH based vaccines are promising candidates for therapy of androgen and estrogen
dependent cancers. We report in this communication development of a novel
recombinant protein vaccine candidate against LHRH. A synthetic gene was designed
in which the codon sequence in the LHRH decapeptide was modified by substituting
the codon for 6-glycine with that of l-leucine. Further the LHRH(6leu) gene was
linked to heat-labile enterotoxin of E. coli (LTB) as carrier. This LHRH(6leu)
LTB gene was cloned into a prokaryotic expression vector under the control of
inducible and strong bacteriophage T7 promoter to over-express LHRH(leu) fused to
LTB as recombinant protein in E. coli. Recombinant LHRH(leu)-LTB protein of ~14
kDa size, was purified from inclusion bodies using in-situ refolding on the
column and Ni-NTA based immobilized affinity chromatography. Western blot
confirmed the immunoreactivity of purified LHRH(leu)-LTB fusion protein with anti
LHRH monoclonal antibody. The vaccine protein was further characterized by mass
spectroscopy, circular dichroism and fluorescence spectroscopy. This
communication reports a recombinant LHRH fusion protein with potential for
blocking of sex hormones production for eventual therapy of sex hormones
dependent neoplasms.
PMID- 28410995
TI - Transcatheter versus surgical aortic valve replacement in patients with non-high
surgical risk severe aortic stenosis: A systematic review.
AB - OBJECTIVE: Transcatether aortic valve replacement (TAVR) has emerged as an
acceptable alternative to surgical aortic valve replacement (SAVR) in patients
with high-risk surgical profile. In this analysis, we compare both approaches in
non-high surgical risk severe aortic stenosis. METHODS: Only studies comparing
SAVR and TAVR and enrolling patients with low-intermediate risk were included
from January 2000 through May 2016. Primary endpoints were assessed at 1 and
12months including: mortality, cerebrovascular accident (CVA) and myocardial
infarction (MI). Secondary endpoints at 1month included: bleeding, acute kidney
injury, new permanent pacemaker implantation and vascular access site
complications. RESULTS: A total of 5223 patients from 8 studies were included (4
prospective and 4 retrospective). There were no significant differences between
TAVR and SAVR at one month in terms of mortality (risk ratio RR 0.91, 95% CI:
0.68 to 1.20), or CVA (RR 0.91, 95% CI 0.68 to 1.21). However, MI was lower in
the TAVR group (RR 0.58, 95% CI 0.34 to 0.99). At 12months, there was no
significant difference between strategies in terms of mortality (RR 0.98, 95% CI
0.84-1.13), CVA (RR1.07, 95% CI 0.85-1.33) or MI (RR 0.78, 95% CI 0.53-1.15).
With regard to secondary outcomes, TAVR was associated with lower rates of
bleeding (RR 0.44, 95% CI 0.22-0.88) and acute kidney injury (RR 0.54, 95% CI
0.31-0.93) but higher need for new permanent pacemaker implantation (RR 2.99, 95%
CI 1.51-5.94) and high rate of vascular access site complications (RR 9.08, 95%
CI 2.03-40.66). CONCLUSION: In severe AS patients with non-high surgical risk,
TAVR has lower risk of MI at one month, but both TAVR and SAVR yielded similar
outcomes at one month in terms of mortality and CVA and at 12months in terms of
mortality, CVA and MI. In regard to secondary outcomes at one month, TAVR has
lower rates of bleeding and acute kidney injury, and higher rates of need for new
permanent pacemakers and high rate of vascular access site complications.
PMID- 28410994
TI - The Role of Oxysterols in Human Cancer.
AB - Oxysterols are oxygenated derivatives of cholesterol formed in the human body or
ingested in the diet. By modulating the activity of many proteins [e.g., liver X
receptors (LXRs), oxysterol-binding proteins (OSBPs), some ATP-binding cassette
(ABC) transporters], oxysterols can affect many cellular functions and influence
various physiological processes (e.g., cholesterol metabolism, membrane fluidity
regulation, intracellular signaling pathways). Therefore, the role of oxysterols
is also important in pathological conditions (e.g., atherosclerosis, diabetes
mellitus type 2, neurodegenerative disorders). Finally, current evidence suggests
that oxysterols play a role in malignancies such as breast, prostate, colon, and
bile duct cancer. This review summarizes the physiological importance of
oxysterols in the human body with a special emphasis on their roles in various
tumors.
PMID- 28410996
TI - Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of
Transcription Factors at Early Stages of Stem Cell Differentiation.
AB - Recruitment of transcription factors (TFs) to repressed genes in euchromatin is
essential to activate new transcriptional programs during cell differentiation.
However, recruitment of all TFs, including pioneer factors, is impeded by
condensed H3K27me3-containing chromatin. Single-cell and gene-specific analyses
revealed that, during the first hours of induction of differentiation of
mammalian embryonic stem cells (ESCs), accumulation of the repressive histone
mark H3K27me3 is delayed after DNA replication, indicative of a decondensed
chromatin structure in all regions of the replicating genome. This delay provides
a critical "window of opportunity" for recruitment of lineage-specific TFs to
DNA. Increasing the levels of post-replicative H3K27me3 or preventing S phase
entry inhibited recruitment of new TFs to DNA and significantly blocked cell
differentiation. These findings suggest that recruitment of lineage-specifying
TFs occurs soon after replication and is facilitated by a decondensed chromatin
structure. This insight may explain the developmental plasticity of stem cells
and facilitate their exploitation for therapeutic purposes.
PMID- 28410998
TI - A retrospective longitudinal analysis of anthropometric and physical qualities
that associate with adult career attainment in junior rugby league players.
AB - OBJECTIVES: To retrospectively compare the longitudinal physical development of
junior rugby league players between the Under 13 and 15 age categories in
relation to their adult career attainment outcome. DESIGN: Retrospective
longitudinal design. METHODS: Fifty-one former junior rugby league players were
retrospectively grouped according to their career attainment outcome as adults
(i.e., amateur, academy or professional). As juniors, players undertook a
physical testing battery on three consecutive annual occasions (Under 13s, 14s,
15s) including height, body mass, sum of four skinfolds, maturation, vertical
jump, medicine ball chest throw, 10-60m sprint, agility 505 and estimated VO2max
. RESULTS: Future professional players were younger than academy players with a
greater estimated VO2max compared to amateur players. Between Under 13s and 15s,
professional players (5.8+/-2.5cm) increased sitting height more than amateur
(4.4+/-2.1cm) and academy (4.1+/-1.4cm) players. Logistic regression analyses
demonstrated improvements in sitting height, 60m sprint, agility 505 and
estimated VO2max between amateur and professional players with a high degree of
accuracy (sensitivity=86.7%, specificity=91.7%). CONCLUSIONS: Findings
demonstrate that the development of anthropometric, maturational and physical
qualities in junior rugby league players aged between 13 and 15 years contributed
to adulthood career attainment outcomes. Results suggest that age, maturity and
size advantages, commonly observed in adolescent focused talent identification
research and practice, may not be sensitive to changes in later stages of
development in order to correctly identify career attainment. Practitioners
should identify, monitor and develop physical qualities of adolescent rugby
league players with long-term athlete development in mind.
PMID- 28410999
TI - Impact of time and work:rest ratio matched sprint interval training programmes on
performance: A randomised controlled trial.
AB - OBJECTIVES: The aim of this study was to examine the effects of a short training
intervention using two repeated sprint protocols matched for total sprint
duration and work:rest ratio. DESIGN: Randomised-controlled trial. METHODS:
Thirty physically active males were randomly allocated to one of two sprint
training groups: a 6s group, a 30s group or a non-exercising control. The
training groups were matched for work:rest ratio and total sprint time per
session, and completed 6 training sessions over a 2-week period. Before and after
the 2 week training period, participants completed a VO2max test and a 10km time
trial on a cycle ergometer. RESULTS: Time trial performance increased
significantly by 5.1% in 6s (630+/-115s to 598+/-92s; p<0.05) and 6.2% in 30s
(579+/-68s to 543+/-85s; p<0.05) from baseline testing, but there was no
significant change in the control group (p>0.05), and no significant difference
between exercise groups (p>0.05). The 6s group increased peak power output by
9.0% (from 1092+/-263W to 1181+/-248W; p<0.05) from sprint session 1 to 6, and
the 30s group by 20.0% (1041+/-161W to 1237+/-159W; p<0.05). CONCLUSIONS: This
study indicates that both 6 and 30s bouts of repeated sprint exercise, matched
for total sprint duration and W:R can improve athletic performance.
PMID- 28411000
TI - Meconium "aspiration" (or respiratory distress associated with meconium-stained
amniotic fluid?).
AB - The designation meconium aspiration syndrome (MAS) reflects a spectrum of
disorders in infants born with meconium-stained amniotic fluid, ranging from mild
tachypnea to severe respiratory distress and significant mortality. The frequency
of MAS is highest among infants with post-term gestation, thick meconium, and
birth asphyxia. Pulmonary hypertension is an important component in severe cases.
Prenatal hypopharyngeal suctioning and postnatal endotracheal intubation and
suctioning of vigorous infants are not effective. Intubation and suctioning of
non-breathing infants is controversial and needs more investigation. Oxygen,
mechanical ventilation, and inhaled nitric oxide are the mainstays of treatment.
Surfactant is often used in infants with severe parenchymal involvement. High
frequency ventilation and extracorporeal membrane oxygenation are usually
considered rescue therapies.
PMID- 28411001
TI - Interstitial lung disease induced by fluoxetine: Systematic review of literature
and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance
database.
AB - We investigated a pulmonary adverse drug reaction possibly induced by fluoxetine,
the Interstitial Lung Disease, by performing a systematic review of published
case reports on this subject, a review of the World Health Organization
VigiAccess database, of the European EudraVigilance database and of a national
Pharmacovigilance database (Italian Pharmacovigilance Network). The research
found a total of seven cases linking fluoxetine to Interstitial Lung Disease in
the literature. 36 cases of interstitial lung disease related to fluoxetine were
retrieved from the VigiAccess database (updated to July 2016), and 36 reports
were found in EudraVigilance database (updated to June 2016). In the Italian
Pharmacovigilance database (updated to August 2016), we found only one case of
Interstitial Lung Disease, codified as "pulmonary disease". Our investigation
shows that fluoxetine might be considered as a possible cause of Interstitial
Lung Disease. In particular, although here we do not discuss the assessment of
benefits and harms of fluoxetine, since this antidepressant is widely used, our
review suggests that fluoxetine-induced Interstitial Lung Disease should be
considered in patients with dyspnea, associated or not with dry cough, who are
treated with this drug. An early withdrawn of fluoxetine could be useful to
obtain a complete remission of this adverse drug reaction and special attention
should be particularly devoted to long-term therapy, and to female and elderly
patients. Although the spontaneous reporting system is affected by important
limitations, drug post- marketing surveillance represents an important tool to
evaluate the real world effectiveness and safety of drugs.
PMID- 28411002
TI - P-gp/ABCB1 exerts differential impacts on brain and fetal exposure to
norbuprenorphine-Response to 'Letter to the Editor'.
PMID- 28410997
TI - International incidence of childhood cancer, 2001-10: a population-based registry
study.
AB - BACKGROUND: Cancer is a major cause of death in children worldwide, and the
recorded incidence tends to increase with time. Internationally comparable data
on childhood cancer incidence in the past two decades are scarce. This study
aimed to provide internationally comparable local data on the incidence of
childhood cancer to promote research of causes and implementation of childhood
cancer control. METHODS: This population-based registry study, devised by the
International Agency for Research on Cancer in collaboration with the
International Association of Cancer Registries, collected data on all
malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years
in populations covered by high-quality cancer registries with complete data for
2001-10. Incidence rates per million person-years for the 0-14 years and 0-19
years age groups were age-adjusted using the world standard population to provide
age-standardised incidence rates (WSRs), using the age-specific incidence rates
(ASR) for individual age groups (0-4 years, 5-9 years, 10-14 years, and 15-19
years). All rates were reported for 19 geographical areas or ethnicities by sex,
age group, and cancer type. The regional WSRs for children aged 0-14 years were
compared with comparable data obtained in the 1980s. FINDINGS: Of 532 invited
cancer registries, 153 registries from 62 countries, departments, and territories
met quality standards, and contributed data for the entire decade of 2001-10. 385
509 incident cases in children aged 0-19 years occurring in 2.64 billion person
years were included. The overall WSR was 140.6 per million person-years in
children aged 0-14 years (based on 284 649 cases), and the most common cancers
were leukaemia (WSR 46.4), followed by CNS tumours (WSR 28.2), and lymphomas (WSR
15.2). In children aged 15-19 years (based on 100 860 cases), the ASR was 185.3
per million person-years, the most common being lymphomas (ASR 41.8) and the
group of epithelial tumours and melanoma (ASR 39.5). Incidence varied
considerably between and within the described regions, and by cancer type, sex,
age, and racial and ethnic group. Since the 1980s, the global WSR of registered
cancers in children aged 0-14 years has increased from 124.0 (95% CI 123.3-124.7)
to 140.6 (140.1-141.1) per million person-years. INTERPRETATION: This unique
global source of childhood cancer incidence will be used for aetiological
research and to inform public health policy, potentially contributing towards
attaining several targets of the Sustainable Development Goals. The observed
geographical, racial and ethnic, age, sex, and temporal variations require
constant monitoring and research. FUNDING: International Agency for Research on
Cancer and the Union for International Cancer Control.
PMID- 28411003
TI - Bryne's grading system predicts poor disease-specific survival of oral squamous
cell carcinoma: a comparative study among different histologic grading systems.
AB - OBJECTIVES: The aim of this study was to access the prognostic value of 4
histopathologic grading systems of oral squamous cell carcinoma (OSCC): The World
Health Organization (WHO), Anneroth, Bryne (1989), and Bryne (1992). STUDY
DESIGN: Eighty-five cases of OSCC diagnosed between 1996 and 2010 at the Clinics
Hospital of Porto Alegre (Porto Alegre, Brazil) were included. Slides stained
with hematoxylin and eosin were obtained, and a histologic grade was assigned on
the basis of the consensus of 3 expert oral pathologists, who were blinded to the
clinicopathologic factors. Each system was correlated with proliferative labeling
index, accessed through Ki67 immunostaining, clinicopathologic factors, patient
outcome (alive or deceased), and survival time. RESULTS: The increase in Bryne
(1992) histologic grades was accompanied by an increase in proliferative labeling
index. Moreover, this system was the only one associated with patient outcome (P
= .01) and survival. Bryne (1992) grading system grade III tumors were associated
with poor disease-specific survival according to univariate and multivariate cox
regression analyses and the log-rank test (P < .05). The other systems evaluated
presented no association with patients' outcome or survival. CONCLUSIONS: The
Bryne (1992) grading system is more effective in predicting survival in OSCC
compared with the systems proposed by the WHO, Anneroth, or Bryne (1989).
PMID- 28411004
TI - Firm, dome-shaped mass of lower lip.
PMID- 28411005
TI - Bacterial and histopathological findings in deep head and neck infections: a
retrospective analysis.
AB - OBJECTIVES: Deep neck infections are among the most dangerous acute diseases in
the head and neck region. This analysis gives an overview of the bacterial and
histopathologic findings of deep neck infections. STUDY DESIGN: From January 2002
to December 2012, 63 patients were diagnosed with and treated for deep neck
infections at the University Medical Center Gottingen. Bacterial and
histopathologic examinations were made, and the occurrence of bacterial pathogens
and histopathologic findings were analyzed. RESULTS: The most commonly isolated
aerobic gram-positive pathogen was Streptococcus viridans (26.7%); Staphylococcus
epidermidis and Staphylococcus aureus were each found in 16.7% of infections. The
most commonly isolated aerobic gram-negative pathogens were Escherichia coli,
Klebsiella oxytoca, and Haemophilus influenzae. In 1.6% of patients, a malignant
cancer was detected. CONCLUSION: For clear diagnosis and effective therapy, a
bacteriologic investigation of deep neck infections is essential because of the
heterogeneous spectrum of the detected bacteria. In contrast to Asia, where
Klebsiella pneumoniae is the most common pathogen, in South Lower Saxony,
Germany, we discovered a dominating spectrum of aerobic gram-positive cocci.
Biopsy obtained from an abscess cavity for histologic examination should always
be part of the diagnostic process in order to exclude a malignant process.
PMID- 28411006
TI - The efficacy of minocycline mouth rinses on the symptoms associated with
recurrent aphthous stomatitis: a randomized, double-blind, crossover study
assessing different doses of oral rinse.
AB - OBJECTIVE: The aim of the study was to assess the efficacy of 2 different
concentrations of minocycline mouthwashes on the symptoms of recurrent aphthous
stomatitis (RAS). STUDY DESIGN: The 2-year study was designed as a randomized,
double-blind, crossover study. Healthy patients with frequent RAS episodes
received 2 sealed and computer-randomized marked kits containing minocycline
mouthwashes (0.2% and 0.5% solution). The patients were asked to use 1 of the
kits on the first episode of RAS, starting with the first onset of prodromal
symptoms, until the symptoms resolved or up to a maximum of 10 days (whichever
came first). The patients were asked to use their second kit during a subsequent
episode. RESULTS: A total of 14 patients (8 males, 6 females) completed the 2
arms of the study. The mean intensity of pain was significantly lower when the
0.5% solution was used compared with the 0.2% solution (P = .027). The difference
reached the level of statistical significance as soon as the end of the second
day of use (P = .032). Only minor and temporary adverse reactions were
documented. CONCLUSIONS: We found that 0.5% minocycline mouth rinse was more
effective than the 0.2% concentration, which had been suggested by our group in
previous studies for the management of RAS.
PMID- 28411007
TI - Influence of lip retraction on the cone beam computed tomography assessment of
bone and gingival tissues of the anterior maxilla.
AB - OBJECTIVE: To evaluate the influence of lip retraction on cone beam computed
tomography (CBCT) assessment of bone and gingival tissues on the labial surface
of the anterior maxilla. STUDY DESIGN: A retrospective study was conducted using
measurements of bone and gingival tissues collected from 120 maxillary incisors.
The thicknesses of the bone and gingival tissues of different regions were
measured on CBCT images, with and without a lip retractor. The thicknesses of the
gingival tissues obtained from CBCT were correlated with measurements performed
by clinical probing. RESULTS: The thickness of bone in the more cervical region
presented a higher mean value for exams performed with a lip retractor (P =
.021). The thickness of bone found a significant correlation with the thickness
of the gingiva (P <= .020) with a lip retractor in CBCT exams. The thickness of
the gingival tissue obtained from CBCT scans with lip retraction found
significant correlations with those obtained clinically (P <= .001). CONCLUSIONS:
The use of lip retractors is a simple and reliable practice that allows the
measurement of gingival tissues on CBCT images. This practice can exempt a
patient from an invasive clinical procedure for measuring the thickness of the
gingival tissue for implant cases of the anterior segment.
PMID- 28411008
TI - Cone beam computed tomography incidental findings of the cervical spine and
clivus: retrospective analysis and review of the literature.
AB - OBJECTIVE: The aim of this study was to analyze and describe incidental findings
in the cervical spine (C-spine) and the clivus encountered in cone beam computed
tomography (CBCT) imaging. The wide range of possible anatomic variants and
pathoses is discussed in the context of the medical and dental literature to
clarify their radiographic appearance and clinical implications as a guide for
the oral and maxillofacial radiologist. STUDY DESIGN: A retrospective analysis of
radiographic reports was conducted based on CBCT images from 2 oral and
maxillofacial imaging centers. Reports documenting incidental findings in the C
spine or the clivus were selected. Data on patient age and sex were collected,
and each incidental finding was categorized as degenerative, congenital, or
developmental/pathologic. Each finding is discussed with clinical importance and
is pictorially presented. RESULTS: From a total of 7689 CBCT reports, there were
732 incidental findings (9.5%) in the C-spine or the clivus. Most findings were
in the C-spine (92.3%), were degenerative in nature (78.7%), and occurred in
females in their sixth decade. Logistic regression analysis showed that the odds
of presenting with a degenerative incidental finding in the C-spine or the clivus
did not differ based on sex but were 5.5 times (95% confidence interval, 3.77
8.04) higher if the patient was aged 50 years or older. CONCLUSIONS: This review
is the largest and the first to characterize incidental findings in the C-spine
and the clivus. Such findings were reported in 9.5% of radiographic reports.
Several presented as uncommon congenital variants that are not usually
spotlighted during oral and maxillofacial radiology training.
PMID- 28411009
TI - Skeletal muscle morphology and regulatory signalling in endurance-trained and
sedentary individuals: The influence of ageing.
AB - Muscle mass in humans is inversely associated with circulating levels of
inflammatory cytokines, but the interaction between ageing and training on muscle
composition and the intra-muscular signalling behind inflammation and contractile
protein synthesis and degradation is unknown. We studied 15 healthy life-long
endurance runners, 12 age-matched untrained controls, 10 young trained and 12
young untrained individuals. Thigh muscle composition was investigated by
magnetic resonance imaging (MRI), where non-contractile intramuscular tissue
(NCIT) area (fat and connective tissue) was found to be greater in older but
lower in trained individuals. Subcutaneous adipose tissue was also lower in
trained individuals but was not affected by age. In vastus lateralis biopsies, no
influence of age or training was found on levels of endomysial collagen,
determined by Sirius Red and Collagen III staining, whereas perimysial
organisation tended to be more complex in older individuals. No clear difference
with training was seen on intramuscular inflammatory signalling, whereas lower
protein levels of NFkB subunits p105, p50 and p65 were observed with ageing. Gene
expression of IL6 and TNFalpha was not different between groups, while IL1
receptor and TNFalpha-receptor1 levels were lower with age. Myostatin mRNA was
lower in older and trained groups, while expression of MuRF1 was lower in trained
individuals and FoxO3 expression was greater in aged groups. The association of
increased muscle NCIT with age-associated muscle loss in humans is not
accompanied by any major alterations in intramuscular signalling for
inflammation, but rather by direct regulatory factors for protein synthesis and
proteolysis in skeletal muscle.
PMID- 28411010
TI - Effects of vitamin D and resveratrol on metabolic associated markers in liver and
adipose tissue from SAMP8 mice.
AB - : SAMP8 mice exhibit multiple metabolic characteristics associated with age, and
it is a suitable candidate for researching aging associated metabolic
dysfunction. OBJECTIVES: We aimed to 1) explore how key metabolic markers will be
altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the
combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated
metabolic impairment in liver and adipose tissue from SAMP8 mice. METHODS: SAMP8
mice and their control SAMR1 mice were divided into 5 groups, i.e. SAMR1, SAMP8,
SAMP8 mice supplemented with VD, RSV and VD combined with RSV group,
respectively. At the end of the intervention, glucose and insulin tolerance, p
AMP-activated protein kinase (AMPK) and amyloid precursor protein (APP), and
endoplasmic reticulum (ER) stress markers in liver and adipose tissue,
adiponectin secretion, p-NF-kappaBp65 and TNF-alpha protein expression in adipose
tissue were determined. RESULTS: Compared to SAMR1 control, SAMP8 mice
demonstrate impaired glucose tolerance and reduction in circulating adiponectin
level; in the liver, SAMP8 mice have reduction in p-Aktser473, elevation in PTP1B
and APP, p-eIF2alpha, GRP78 and p-JNK protein expression. In epididymal (EPI)
fat, SAMP8 mice also have elevated p-Aktser473 and PTP1B compared to SAMR1 mice.
In both epididymal (EPI) and subcutaneous (SC) fat, there were elevated ER stress
markers, reduced p-AMPK and elevated APP, as well as elevated p-NF-kappaBp65 and
TNF-alpha protein expression from SAMP8 compared to SAMR1 mice. In liver, the
combined intervention significantly restored p-Aktser473, p-eIF2alpha and p-JNK
protein expression. In both EPI and SC fat, the combined intervention is
effective for reducing p-NF-kappaB p65 and TNF-alpha in both fat depot, while
only partially reduced ER stress markers in SC fat. As for adiponectin, their
combination is unable to reverse reduction in adiponectin level. Adiponectin
secretion in SC fat from VD, RSV and VDRSV group were also significantly reduced
compared to SAMR1. CONCLUSION: The combined intervention might exert greater
beneficial effects for reversing aging associated metabolic dysfunction in liver
and adipose tissue from SAMP8 mice.
PMID- 28411011
TI - Managerial skills of new practitioner pharmacists within community practice.
AB - OBJECTIVES: To identify managerial skills required in community pharmacy
practice, explore new practitioners' previous exposure to these skills, and
assess new practitioners' perceived preparedness to take on managerial
responsibilities. METHODS: A survey was developed with the use of Qualtrics and
distributed by state pharmacy associations using a convenience sample of
pharmacists from Iowa, Kentucky, Michigan, Ohio, and Pennsylvania. Pharmacists
not practicing in a community pharmacy setting at the time of the study were
excluded. New practitioners were defined as pharmacists practicing for no more
than 10 years. RESULTS: A total of 168 pharmacists completed the survey. More
than one-half (56%) of respondents self-reported being in a managerial position,
and 90% of respondents thought that managerial skills were always or very often
necessary. At graduation, 15% of respondents rated their managerial skill
proficiency to be high to very high, with this increasing to 57% at current point
in their career. When comparing managers versus non-managers, 78% of skills
assessed showed higher utilization in managers. Interestingly, only 44% of skills
showed a higher proficiency in managers. Finally, 88% of respondents thought that
their managerial skills could be improved. CONCLUSION: New practitioners in
community practice reported a high utilization of managerial skills, as well as
improved proficiency throughout their careers. These skills are important in both
community pharmacy training and practice. Managers reported higher utilization of
managerial skills, but that utilization did not always correlate with
proficiency. This highlights the need to further identify and improve managerial
skills during pharmacy education and as part of ongoing continuing professional
development.
PMID- 28411012
TI - Look-alike/sound-alike dietary supplements.
PMID- 28411013
TI - Physician-reported factors that encourage collaboration with community
pharmacists.
AB - OBJECTIVE: To determine factors that encourage physicians to establish
collaborative practice agreements with community pharmacists. METHODS: A 20-item
cross-sectional survey was mailed to a random sample of 1000 family medicine
physicians practicing in North Carolina. Two weeks after the initial mailing, a
reminder was sent to physicians. Physicians were entered into a drawing to
receive a gift card as an incentive for survey completion. The questionnaire
collected demographic information, factors important to physicians for
collaboration with a community pharmacist, and physician perceptions of
pharmacist qualifications. Descriptive statistics were used to analyze patterns
in the Likert scale survey responses. RESULTS: Of the 1000 mailed surveys, 67
were returned as undeliverable, resulting in a final sample size of 933 surveys.
One hundred forty-six family medicine physicians responded to the survey,
yielding a 15.6% response rate. Respondents were 58% male, 73% had been
practicing longer than 10 years, and 60% had an academic affiliation. Our results
indicate that an established relationship with a community pharmacist is the most
important factor when considering a collaborative practice agreement. At least
90% of physicians reported that the most important pharmacist contributions were
drug therapy adverse effect management, drug interaction management, medication
access assistance, prescription counseling, and medication adherence. A majority
of physicians reported that community pharmacists improve quality outcomes and
metrics (74% and 72%, respectively). CONCLUSION: Physicians in North Carolina
recognize the value of the services a pharmacist can provide to their patients.
Developing relationships between community pharmacists and physicians and
describing the value of additional credentialing in the provision of patient care
will be integral in establishing collaborative practice agreements in the
community setting.
PMID- 28411014
TI - Impact of the Act FAST stroke campaign delivered by student pharmacists on the
primary prevention of stroke.
AB - OBJECTIVES: To evaluate the impact of an Act FAST educational intervention
performed by student pharmacists on knowledge of stroke recognition and
management. DESIGN: Stroke preparedness and knowledge of primary prevention were
assessed with the use of pre- and post-intervention surveys targeting community
members at health fairs. The intervention was an Act FAST educational session
with blood pressure and blood glucose screenings provided by student pharmacists.
Act FAST is a quick tool to help recognize and respond to a stroke. The acronym
FAST stands for Face, Arms, Speech, and Time. SETTING: Community health fairs in
Vallejo, CA. PARTICIPANTS: Community members 18 years of age and older.
INTERVENTION: Act FAST educational session delivered by student pharmacists. MAIN
OUTCOME MEASURES: Knowledge of signs, symptoms, management, and risk factors of
strokes as defined by the American Heart Association. RESULTS: Following the Act
FAST educational intervention, total knowledge of signs, symptoms, and management
of stroke significantly increased from moderate to high (n = 112; 95% confidence
interval [CI] 1.419-2.188; P <0.0001). Total knowledge of risk factors of stroke
also significantly increased following the educational intervention (n = 88; 95%
CI 0.6496-1.746; P <0.0001). CONCLUSION: The Act FAST educational intervention
delivered by student pharmacists increased knowledge of signs, symptoms,
immediate management, and modifiable risk factors of stroke. This suggests that
student pharmacists may have a positive impact on community members' preparedness
and knowledge of primary prevention of stroke. The Act FAST campaign may be a
useful tool for all training health care professionals.
PMID- 28411015
TI - Pharmacist contributions to the ten essential services of public health in three
National Association of Boards of Pharmacy regions.
AB - BACKGROUND: Pharmacists have contributed to improved population health through
the delivery of public health services, but their contributions often go
unrecognized within the larger health care system. OBJECTIVES: To determine
pharmacist perceptions of their contributions to the 10 essential services of
public health and to compare those contributions among pharmacists in Iowa, North
Dakota, and Manitoba. METHODS: Licensed pharmacists in Iowa, North Dakota, and
Manitoba were sent an online survey of their perceived level of achievement of
the 10 essential services of public health. RESULTS: A total of 649 pharmacists
completed the survey. The 3 essential services that scored the highest overall
were enforce laws and regulations that protect health and ensure safety, inform
and educate people about health issues, and participate in ongoing training
beyond continuing education requirements. Contributions of pharmacists to the 10
essential services of public health were previously evaluated by frequency of
citation in the published literature. There was relative agreement between what
was reported in the literature and what was determined by survey. One exception
was "enforce laws and regulations that protect health and ensure safety," which
was rarely reported in the literature but was reported in the survey to be the
most frequently delivered service. CONCLUSION: Pharmacist contributions to
improved population health should be reported with the use of the 10 essential
services of public health. This will increase recognition of pharmacist
contributions and better align the disciplines of pharmacy and public health. In
particular, pharmacists should consider ways to increase their level of
involvement in the community and in partnership with other health care
professionals.
PMID- 28411016
TI - Gene Therapy for Hemophilia.
AB - The X-linked bleeding disorder hemophilia causes frequent and exaggerated
bleeding that can be life-threatening if untreated. Conventional therapy requires
frequent intravenous infusions of the missing coagulation protein (factor VIII
[FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a
lasting cure through gene therapy has long been sought. After a series of
successes in small and large animal models, this goal has finally been achieved
in humans by in vivo gene transfer to the liver using adeno-associated viral
(AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic,
and in some cases curative, expression. At the same time, cellular immune
responses against the virus have emerged as an obstacle in humans, potentially
resulting in loss of expression. Transient immune suppression protocols have been
developed to blunt these responses. Here, we provide an overview of the clinical
development of AAV gene transfer for hemophilia, as well as an outlook on future
directions.
PMID- 28411017
TI - Biological properties of propolis extracts: Something new from an ancient
product.
AB - Natural products are an interesting source of new therapeutics, especially for
cancer therapy as 70% of them have botany origin. Propolis, a resinous mixture
that honey bees collect and transform from tree buds, sap flows, or other
botanical sources, has been used by ethnobotany and traditional practitioners as
early in Egypt as 3000 BCE. Enriched in flavonoids, phenol acids and terpene
derivatives, propolis has been widely used for its antibacterial, antifungal and
anti-inflammatory properties. Even though it is a challenge to standardize
propolis composition, chemical analyses have pointed out interesting molecules
that also present anti-oxidant and anti-proliferative properties that are of
interest in the field of anti-cancer therapy. This review describes the various
geographical origins and compositions of propolis, and analyzes how the main
compounds of propolis could modulate cell signaling. A focus is made on the
putative use of propolis in prostate cancer.
PMID- 28411018
TI - Charge-tagging liquid chromatography-mass spectrometry methodology targeting
oxysterol diastereoisomers.
AB - The introduction of a hydroxy group to the cholesterol skeleton introduces not
only the possibility for positional isomers but also diastereoisomers, where two
or more isomers have different configurations at one or more of the stereocentres
but are not mirror images. The differentiation of diastereoisomers is important
as differing isomers can have differing biochemical properties and are formed via
different biochemical pathways. Separation of diasterioisomers is not always easy
by chromatographic methods Here we demonstrate, by application of charge-tagging
and derivatisation with the Girard P reagent, the separation and detection of
biologically relevant diastereoisomers using liquid chromatography - mass
spectrometry with multistage fragmentation.
PMID- 28411020
TI - Paired editorial: Do sleeve gastrectomy and gastric bypass influence treatment
with proton pump inhibitors 4 years postsurgery? A nationwide cohort.
PMID- 28411019
TI - Comparison of surgical outcomes of three different stump closure techniques
during distal pancreatectomy.
AB - BACKGROUND: To find the appropriate method of pancreatic transection during
distal pancreatectomy (DP), we retrospectively compared post-operative
complications including postoperative pancreatic fistula (POPF) according to the
different types of pancreatic transection. METHODS: This study included 169
patients who underwent pancreatic transection using an ultrasonic activated
device (USAD) with transfixion of the pancreatic duct (DP-TF group, n = 89), USAD
followed by pancreaticogastrostomy (DP-PG group, n = 44), and a reinforced linear
tristapler (DP-ST, n = 36). RESULTS: Overall and POPF-related complications in DP
PG group, and delayed gastric emptying (DGE) in DP-ST group were significantly
lower than DP-TF group. There were no significant difference in overall
complication, length of hospitalization and operative costs between DP-PG and DP
ST groups. Operative time was significantly longer in DP-PG group than others.
CONCLUSION: Both DP-PG and DP-ST are associated with better surgical outcomes.
Regarding ease of surgical technique, shorter operative times, and similar
medical costs, DP with a reinforced linear tristapler is a good choice during DP.
PMID- 28411021
TI - Improvement in cardiovascular risk in women after bariatric surgery as measured
by carotid intima-media thickness: comparison of sleeve gastrectomy versus
gastric bypass.
AB - BACKGROUND: Bariatric surgery may diminish cardiovascular risk (CVR) and its
associated mortality. However, studies that compare these effects with different
techniques are scarce. OBJECTIVE: To evaluate the changes in CVR as estimated by
carotid intima-media thickness (IMT) after obesity surgery in women with high CVR
as defined by the presence of metabolic syndrome. SETTING: Academic hospital.
METHODS: We studied 40 severely obese women, of whom 20 received laparoscopic
Roux en Y gastric bypass (RYGB) and 20 received sleeve gastrectomy (SG). Twenty
control women matched for age and cardiovascular risk were also included.
Patients and controls were evaluated at baseline and 1 year after surgery or
conventional treatment with diet and exercise, respectively. Only 18 of the 20
women in the control group were available for analysis after 1 year. None of the
women who had bariatric surgery was lost to follow-up. RESULTS: Mean carotid IMT
decreased 1 year after surgery irrespective of the surgical technique used,
whereas no changes were observed in the control women who had conventional
therapy (Wilks' lambda = .802, P = .002 for the interaction, P = .011 for RYGB
versus controls, P = .002 for SG versus controls, P = .349 for RYGB versus SG).
CONCLUSION: Both RYGB and SG decrease CVR as measured by carotid IMT in obese
women.
PMID- 28411022
TI - The prevalence of obesity and metabolic syndrome in Tibetan immigrants living in
high altitude areas in Ladakh, India.
AB - OBJECTIVE: To examine the prevalence of obesity and related cardiovascular
disease risk factors among Tibetan immigrants living in high altitude areas.
RESEARCH METHODS & PROCEDURES: A total of 149 Tibetan immigrants aged 20 years
and over were recruited in 2016 in Ladakh, India. Anthropometric indices and
biochemical factors were measured. Using the provided Asia-Pacific criteria from
the World Health Organization, overweight and obese status were determined.
Metabolic syndrome (MetS) was defined according to the American Heart
Association. RESULTS: In general, men were older, taller, and had a greater
amount of fasting glucose, and uric acid when compared to women. The prevalence
of overweight, general obesity, and central obesity was 23.4, 42.6, and 42.6% in
men and 7.8, 64.7, and 69.6% in women, respectively. The prevalence of MetS was
10.6% in men and 33.3% in women, respectively. In older subjects, the prevalence
of obesity and MetS was found to be greater. In both genders, the prevalence of
hypertension, central obesity, and MetS was significantly different among these
body mass index (BMI) groups. Compared to the non-central obesity group, the
central obesity group has higher weight, BMI, body fat, hip circumference,
systolic and diastolic BP, and prevalence of hypertension. No relationship was
found between the prevalence of diabetes and fasting glucose and BMI groups or
central obesity groups in both genders. CONCLUSIONS: Among this group of Tibetan
immigrants living in high altitude areas, women have a higher prevalence of
obesity and MetS than men. No relationship was found between diabetes and
obesity.
PMID- 28411023
TI - Comparison of bioelectrical impedance and DXA for measuring body composition
among adults with Down syndrome.
AB - BACKGROUND: Individuals with Down syndrome (DS) have been shown to display high
levels of adiposity and a unique body shape. Laboratory methods used to evaluate
body composition might be too cumbersome for this special population. Therefore,
field methods are desired due to their non-invasive nature. OBJECTIVE: to
determine the agreement between dual energy x-ray absorptiometry (DXA) and
bioelectrical impedance analysis (BIA) for measuring body fat percentage BF% and
fat-free mass (FFM) among adults with DS. METHODS: Twenty-one adults (male: n =
10; female: n = 11) with DS participated in this study. BF% and FFM were
determined by DXA and BIA. RESULTS: There was a significant mean difference
between DXA and BIA for BF% (41.33 +/- 8.98% and 34.23 +/- 9.22%, respectively)
and FFM (41.80 +/- 8.74 kg and 46.95 +/- 9.92 kg, respectively). The correlation
between the two devices for BF% and FFM were significant (r = 0.89 and r = 0.94,
respectively, p < 0.001 for both). The standard error of estimate and total error
values were 4.38% and 8.27%, respectively, for BF% and 3.04 kg and 6.13 kg,
respectively, for FFM. The 95% limits of agreement ranged from -15.64% below to
1.46% above the constant error (CE) of -7.09% for BF% and from -1.52 kg below to
11.83 kg above the CE of 5.15 kg for FFM. CONCLUSIONS: The significant mean
differences and large amount of individual error suggest that BIA may not be an
appropriate surrogate body composition measure compared to DXA in adults with DS.
PMID- 28411024
TI - EpCAM controls morphogenetic programs during zebrafish pronephros development.
AB - Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is
dynamically expressed in human and murine renal epithelia during development. The
levels of EpCAM in the renal epithelium are upregulated both during regeneration
after ischemia/reperfusion injury and in renal-derived carcinomas. The role of
EpCAM in early kidney development, however, has remained unclear. The zebrafish
pronephros shows a similar segmentation pattern to the mammalian metanephric
nephron, and has recently emerged as a tractable model to study the regulatory
programs governing early nephrogenesis. Since EpCAM shows persistent expression
in the pronephros throughout early development, we developed a method to study
the global changes in gene expression in specific pronephric segments of wild
type and EpCAM-deficient zebrafish embryos. In epcam mutants, we found 379
differentially expressed genes. Gene ontology analysis revealed that EpCAM
controls various developmental programs, including uretric bud development,
morphogenesis of branching epithelium, regulation of cell differentiation and
cilium morphogenesis.
PMID- 28411025
TI - Klotho down-regulates Egr-1 by inhibiting TGF-beta1/Smad3 signaling in high
glucose treated human mesangial cells.
AB - Diabetic kidney disease (DKD) has become the leading cause of end-stage renal
disease worldwide and is associated with glomerular mesangial cell (MC)
proliferation and excessive extracellular matrix (ECM) production. Klotho can
attenuate renal fibrosis in part by inhibiting TGF-beta1/Smad3 signaling in DKD.
Early growth response factor 1 (Egr-1) has been shown to play a key role in renal
fibrosis in part by facilitating the formation of a positive feedback loop
involving TGF-beta1. However, whether Klotho down-regulates Egr-1 by inhibiting
TGF-beta1/Smad3 signaling in DKD is unclear. In the present study, we assessed
human MCs that were incubated under high-glucose conditions to mimic diabetes.
Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or
knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN),
collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and
protein expression levels were determined by RT-qPCR and western blotting
respectively. High glucose time-dependently down-regulated Klotho mRNA and
protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated
Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p
Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up
regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover,
the effects of si-Klotho on Egr-1 expression were abolished by the TGF-beta1
inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production
in high-glucose-treated human MCs, an effect that has been partially attributed
to Egr-1 down-regulation facilitated by TGF-beta1/Smad3 signaling inhibition.
PMID- 28411026
TI - Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus
cells by promoting mitochondrial translocation of p53 and nuclear translocation
of AIF.
AB - Compression-induced programmed cell death of nucleus pulposus (NP) cells is an
important contributor to intervertebral disc degeneration (IDD). Dynamin-related
protein 1 (Drp1), a crucial mitochondrial fission protein, triggers programmed
necrosis upon cellular injury. However, limited information is available about
the role of Drp1 in compression-induced programmed necrosis of NP cells. In the
present study, we found that compression resulted in upregulation and
mitochondrial translocation of Drp1. Inhibition of Drp1 by siRNA or mitochondrial
division inhibitor 1 (mdivi-1) effectively prevented the programmed necrosis of
NP cells treated with compression. Furthermore, Drp1 promoted mitochondrial
translocation of p53 and nuclear translocation of apoptosis-inducing factor (AIF)
in compression-treated NP cells. Inhibition of p53 mitochondrial translocation by
pifithrin-MU (PFT-MU) and silencing of AIF expression by siRNA significantly
alleviated compression-induced NP cell programmed necrosis. These data indicates
that Drp1 mediates compression-induced programmed necrosis of NP cells by
promoting mitochondrial translocation of p53 and nuclear translocation of AIF.
PMID- 28411027
TI - beta-caryophyllene reduces atherogenic index and coronary risk index in
hypercholesterolemic rats: The involvement of cardiac oxidative damage.
AB - Hypercholesterolemia and cardiac oxidative damage have been implicated in the
pathophysiology of atherosclerosis. In earlier studies, treatment using natural
phytocannabinoid beta-caryophyllene caused a hypolipemic effect, as well as
ameliorated hepatic oxidative damage. In this regard, the present study aimed to
investigate whether beta-caryophyllene treatment was able to protect the cardiac
tissue against hypercholesterolemic atherosclerosis, and to investigate the
involvement of antioxidant mechanisms in this effect using a model of
hypercholesterolemia induced by Triton WR-1339. The hypercholesterolemic animals
exhibited a significant increase in the cholesterol (TC), triglycerides (TG) and
free fatty acids (FFA) contents in cardiac tissue, as well as showed significant
increase on atherogenic index (AI) and coronary risk index (CRI). Moreover,
cardiac levels of reactive oxygen species (ROS) and thiobarbituric acid reactive
substances (TBARS) were increased in hypercholesterolemic animals, while the
glutathione reduced (GSH) levels and glutathione peroxidase (GPx) activity were
decreased. beta-caryophyllene treatment reduced the cardiac lipid content, as
well as decreased the AI and CRI. Moreover, the treatment was able to improve the
antioxidant/oxidant status in heart tissue of hypercholesterolemic animals. In
summary, beta-caryophyllene possesses antioxidant properties, preventing lipidic
oxidative damage and ameliorating the GPx activity, an important enzyme linked to
the prevention of atherosclerosis. Thus, this compound can be used as an attempt
to prevent or reduce atherosclerosis in hypercholesterolemic rats.
PMID- 28411028
TI - Extensive diversity of rickettsiales bacteria in ticks from Wuhan, China.
AB - Rickettsiales bacteria are important agents of (re)emerging infectious diseases,
with ticks playing a key role in their evolution and transmission. We collected
1079 hard ticks belonging to five species (Ixodes sinensis, Rhipicephalus
microplus, Haemaphysalis flava, Haemaphysalis hystricis and Haemaphysalis
longicornis) from cattle and goats in Wuhan city, Hubei province, China. The
dominant tick species was H. longicornis (578, 53.57%), followed by R. microplus
(354, 32.81%), H. hystricis (62, 5.75%), H. flava (57, 5.28%), and I. sinensis
(28, 2.59%). Rickettsiales bacteria were identified in these ticks by amplifying
the Rickettsiales 16S rRNA (rrs), citrate synthase (gltA), and heat shock protein
(groEL) genes. The rrs gene of Rickettsiales was positive in 32 (2.97%) ticks,
including 2 cases of co-infection, with 4 (0.69%) in H. longicornis, 15 (4.24%)
in R. microplus, 7 (12.28%) in H. flava, 1 (1.61%) in H. hystricis, and 5
(17.86%) in I. sinensis ticks. Phylogenetic analysis revealed the presence of six
recognized and seven Candidatus species of Rickettsiaceae, Anaplasmataceae and
Candidatus Midichloriaceae. Notably, one lineage within both Ehrlichia and
Candidatus Midichloriaceae was distinct from any known Rickettsiales, suggesting
the presence of potentially novel species of Rickettsiales bacteria. In sum,
these data reveal an extensive diversity of Rickettsiales in ticks from Wuhan,
highlighting the need to understand Rickettsiales infection in local animals and
humans.
PMID- 28411030
TI - A critical and interpretive literature review of birthing women's non-elicited
pain language.
AB - BACKGROUND: Standardised pain assessment i.e. the McGill Pain Questionnaire
provide an elicited pain language. Midwives observe spontaneous non-elicited pain
language to guide their assessment of how a woman is coping with labour. This
paper examined the labour pain experience using the questions: What type of pain
language do women use? Do any of the words match the descriptors of standardised
pain assessments? What type of information doverbal and non-verbal cues provide
to the midwife? METHODS: A literature search was conducted in 2013. Studies were
included if they had pain as the primary outcome and examined non-elicited pain
language from the maternal perspective. A total of 12 articles were included.
FINDINGS: The analysis revealed six categories in which labour pain can be
viewed: 'positive', 'negative', 'physical', 'emotional', 'transcendent' and
'natural'. Women's language comprised i.e. prefixes and suffixes, which indicate
the qualities of pain, and figurative language. Language indicated location of
pain, gave insight into other life phenomena i.e. death, and shared similarities
with standardised pain assessmentdescriptors. Labour cues were 'functional',
'dysfunctional,' or 'neutral' (part of the physiological childbirth process), and
were verbal, non-verbal, emotional, psychological, physical behaviour or
reactions, or tactile. CONCLUSION: Labour can bring about a spectrum of
sensations and therefore emotions from happiness and pleasure to suffering and
grief. Spontaneous pain language comprises verbal language and non-verbal
behaviour. Narratives are an effective form of pain communication in that they
provide details regarding the quality, nature and dimensions of pain, and details
notcaptured in quantitative data.
PMID- 28411029
TI - Clinical and Economic Impact of a Multisciplinary Intervention to Reduce Bleeding
Risk in Patients With Acute Coronary Syndrome.
AB - INTRODUCTION AND OBJECTIVES: To evaluate the clinical and economic impact of a
multidisciplinary program to reduce bleeding events in patients with acute
coronary syndrome through optimization of antithrombotic therapy. METHODS: We
designed a preintervention (PRE) and postintervention (POST) quasi-experimental
study using a retrospective analysis of 2 cohorts. The first cohort was analyzed
to detect correctable measures contributing to bleeding (PRE). Afterward, a
quality improvement intervention with a bundle of recommendations was
implemented. Finally, a second cohort of patients was evaluated to investigate
the impact of the measures on bleeding reduction (POST). The impact on health
outcomes was evaluated through comparison of the percentage of in-hospital
bleeding events and 30-day readmissions between the 2 cohorts. The economic
analysis took into account the costs associated with the implementation of the
program and the cost-savings associated with the prevention of bleeding events
and 30-day readmissions. RESULTS: A total of 677 patients were included (377 in
PRE and 300 in POST). The total bleeding rate was reduced after the
implementation of the bundled intervention by 29.2% (31.6% in POST vs 22.3% in
PRE; OR, 0.62; 95%CI, 0.44-0.88) while 30-day readmission rates were 7.7% in PRE
and 5% in POST (P=.20). The estimated avoided cost was ?95 113.6 per year,
meaning that ?10.1 would be obtained in return for each euro invested during the
first year and ?36.3 during the following years. CONCLUSIONS: This
multidisciplinary program has proven to be effective in reducing bleeding events
and is economically attractive.
PMID- 28411031
TI - Prognostic value of visually detected coronary artery calcification on unenhanced
non-gated thoracic computed tomography for prediction of non-fatal myocardial
infarction and all-cause mortality.
AB - PURPOSE: To determine the prognostic value of visually detected coronary artery
calcification (CAC) on unenhanced non-gated thoracic computed tomography (CT) for
non-fatal myocardial infarction (MI) and all-cause mortality. METHODS: This
retrospective single-centre cohort study comprised of 410 consecutive patients
aged 40-80 years without any known cardiovascular disease at baseline. CT images
without electrocardiogram-gating were acquired for a variety of respiratory
medicine indications. CAC was examined by a single reader blinded to clinical
data and outcome, using 1) the Agatston coronary calcium score (CCS), 2) visual
CAC and 3) number of visually calcified coronary arteries. RESULTS: Visible CAC
was identified in 201 (49.0%) of the 410 patients (60.5 +/- 10.0 years old, 42.4%
males). After a median follow up of 7.0 years, 39 patients (9.5%) experienced an
event (death or non-fatal MI). After adjustment for cardiovascular risk factors,
those with 1) higher CCS, 2) presence of visual CAC or 3) greater number of
calcified coronary arteries by visual assessment, had an increased risk of
adverse outcome (all p-value <0.05). There was no significant difference in c
statistics of the three methods of assessment (0.81, 0.80, 0.81 respectively),
indicating that simple visual assessment of CAC may have a prognostic value
similar to CCS. CONCLUSION: Among patients with no known cardiovascular disease
who underwent unenhanced non-gated CT for a pulmonary-related indication,
visually detected CAC was a strong independent predictor of non-fatal MI and all
cause mortality.
PMID- 28411032
TI - A 2-bp insertion (c.67_68insCC) in MC1R causes recessive white coat color in Bama
miniature pigs.
PMID- 28411033
TI - Significant differences of function and expression of microRNAs between ground
state and serum-cultured pluripotent stem cells.
AB - Serum- and 2i-cultured embryonic stem cells (ESCs) show different epigenetic
landscapes and transcriptomic profiles. The difference in the function and
expression of microRNAs (miRNAs) between these two states remains unclear. Here,
we showed that 2i- and serum-cultured ESCs exhibited distinctive miRNA expression
profiles with >100 miRNAs differentially expressed, and the expression changes
were largely due to transcriptional regulation. We further characterized the
function of miRNAs differentially expressed under two conditions and found that
ESCs exhibited higher degree of dependency on miRNAs for rapid proliferation;
since Dgcr8-/- or Dicer1-/- but not wild-type ESCs showed slower growth rate and
more accumulation in the G1 phase under 2i than serum condition. More
interestingly, introduction of various self-renewal-silencing miRNAs in wild-type
or Dgcr8-/- ESCs failed to silence the self-renewal in 2i medium, but regained
the ability to silence the self-renewal upon the addition of serum. Our findings
reveal significant differences in the expression and function of miRNAs between
serum- and 2i-cultured ESCs.
PMID- 28411034
TI - Task-optimal auditory attention set restored as fast in older as in younger
adults after distraction.
AB - The present study investigated how fast younger and older adults recovered from a
distracted attentional state induced by rare, unpredictable sound events. The
attentional state was characterized by the auditory N1 event-related potential
(ERP), which is enhanced for sound events in the focus of attention. Younger (19
26 years) and older (62-74 years) adults listened to continuous tones containing
rare pitch changes (glides) and short gaps. Glides and gaps could be separated in
150ms, 250ms, 650ms or longer and the task was gap detection while ignoring
glides. With longer glide-gap separations similar N1 enhancements were observable
in both groups suggesting that the duration of the distracted sensory state was
not affected by aging. Older adults responded, however, slower at short glide-gap
separations which indicated that distraction at subsequent levels of processing
may have nonetheless more impact in older than in younger adults.
PMID- 28411035
TI - Altered ion transport in normal human bronchial epithelial cells following
exposure to chemically distinct metal welding fume particles.
AB - Welding fume inhalation causes pulmonary toxicity, including susceptibility to
infection. We hypothesized that airway epithelial ion transport is a target of
fume toxicity, and investigated the effects of fume particulates from manual
metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion
transport in normal human bronchial epithelium (NHBE) cultured in air-interface.
MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn;
GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167
166.7MUg/cm2) were applied apically to NHBEs. After 18h transepithelial potential
difference (Vt), resistance (Rt), and short circuit current (Isc) were measured.
Particle effects on Na+ and Cl- channels and the Na+,K+,2Cl--cotransporter were
evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid
(NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167
16.7MUg/cm2) increased basal Vt. Only 16.7MUg/cm2 GMA-MS increased basal Vt
significantly. MMA-SS or GMA-MS exposure potentiated Isc responses (decreases) to
amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser
degree than MMA-SS. Variable effects on Rt were observed in response to
amiloride, and bumetanide. Generally, MMA-SS was more potent in altering
responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in
the absence of LDH release, but decreases in Vt, Rt, and Isc at higher fume
particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus,
Na+ transport and Na+,K+,2Cl--cotransport are affected by fume exposure; MMA-MS
is more potent than GMA-MS. Enhanced Na+ absorption and decreased airway surface
liquid could compromise defenses against infection.
PMID- 28411037
TI - Carotid Plaque Evaluation Using Gemstone Spectral Imaging: Comparison with
Magnetic Resonance Angiography.
AB - BACKGROUND: The present study compared the applicability of computed tomography
carotid plaque imaging using effective Z maps with gemstone spectral imaging
(GSI) to that of magnetic resonance plaque imaging using 3-dimensional time-of
flight magnetic resonance angiography. METHODS: Stenosis was assessed in 18
carotid arteries of 14 patients, and the effective Z values of noncalcified
carotid plaques were compared with the signal intensities of magnetic resonance
angiography. RESULTS: It was found that the effective Z value of noncalcified
carotid plaques was significantly lower for a group with high signal intensity
than for a group with low signal intensity on magnetic resonance angiography (P
<.001). The area under the receiver operating characteristic curve of effective Z
values was .975, and the presumed cutoff effective Z value required to
discriminate low and high intensity plaques on magnetic resonance angiography was
7.83. CONCLUSIONS: The effective Z value generated by GSI is a useful parameter
to detect vulnerable carotid plaque materials.
PMID- 28411036
TI - Prolonged particulate chromate exposure does not inhibit homologous recombination
repair in North Atlantic right whale (Eubalaena glacialis) lung cells.
AB - Chromosome instability is a common feature of cancers that forms due to the
misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a
high fidelity DNA repair pathway that utilizes a homologous DNA sequence to
accurately repair such damage and protect the genome. Prolonged exposure (>72h)
to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits
HR repair, resulting in increased chromosome instability in human cells.
Comparative studies have shown acute Cr(VI) exposure induces less chromosome
damage in whale cells than human cells, suggesting investigating the effect of
this carcinogen in other species may inform efforts to prevent Cr(VI)-induced
chromosome instability. Thus, the goal of this study was to determine the effect
of prolonged Cr(VI) exposure on HR repair and clastogenesis in North Atlantic
right whale (Eubalaena glacialis) lung cells. We show particulate Cr(VI) induces
HR repair activity after both acute (24h) and prolonged (120h) exposure in North
Atlantic right whale cells. Although the RAD51 response was lower following
prolonged Cr(VI) exposure compared to acute exposure, the response was sufficient
for HR repair to occur. In accordance with active HR repair, no increase in
Cr(VI)-induced clastogenesis was observed with increased exposure time. These
results suggest prolonged Cr(VI) exposure affects HR repair and genomic stability
differently in whale and human lung cells. Future investigation of the
differences in how human and whale cells respond to chemical carcinogens may
provide valuable insight into mechanisms of preventing chemical carcinogenesis.
PMID- 28411038
TI - Long-Term Impact of Implementation of a Stroke Protocol on Door-to-Needle Time in
the Administration of Intravenous Tissue Plasminogen Activator.
AB - BACKGROUND: This study aims to evaluate the effectiveness of implementing a
stroke protocol (SP) in improving door-to-needle time (DTNT) and door-to-computed
tomography (DTCT) time from 2010 to 2014. Published data from the Get With The
Guidelines-Stroke (GWTGS) participating hospitals showed that median DTNT = 75
minutes with 26.6% of the patients achieving the recommended DTNT of 60 minutes
or less. Implementation of an SP, which specifies the role of nurses, physicians,
and technicians during acute stroke evaluation, can improve DTNT. METHODS: This
longitudinal quality assurance study was designed to compare the DTNT and the
DTCT time pre- and post implementation of an SP in our hospital. Patients' data
before (2009-2010) and after (2010-2014) the implementation of an SP were
collected each year during the same 6-month period and compared using statistical
software SPSS 20.0 for Windows (SPSS Inc., Chicago, IL). RESULTS: Although our
DTNT did not significantly improve over the years, the median DTNT (59 minutes)
was much less than the reported 75 minutes of GWTGS hospitals. Our DTCT time
diminished from 20.6 minutes in 2009 to 15.9 minutes in 2014. The percentage of
patients with a DTNT of 1 hour or less did not differ among all years (P = .296)
and was 55.8%. CONCLUSIONS: Our study suggests that our performance in evaluating
acute ischemic stroke patients within the American Heart Association/American
Stroke Association suggested time window is reachable for prolonged periods of
time. Continuous monitoring and education of all players involved are crucial to
ensure best possible outcomes in the timely administration of intravenous tissue
plasminogen activator.
PMID- 28411039
TI - The Prevalence of Self-Reported Stroke in the Australian National Eye Health
Survey.
AB - BACKGROUND AND PURPOSE: The study aimed to determine the prevalence of and risk
factors for self-reported stroke in Indigenous and non-Indigenous Australians.
RESEARCH DESIGN AND METHODS: In this national eye study, 1738 Indigenous
Australians (41.1% male) aged 40-92 years and 3098 non-Indigenous Australians
(46.4% male) aged 50-98 years from 30 randomly selected sites, stratified by
remoteness, were recruited and examined. Sociodemographic information and a
history of stroke, diabetes, and ocular health were obtained using an interviewer
administered questionnaire. RESULTS: The crude prevalence of self-reported stroke
was 5.04% (156 of 3098, 95% confidence interval: 4.29%-5.87%) for non-Indigenous
Australians and 8.75% (152 of 1738, 95% confidence interval: 7.46%-10.17%) for
Indigenous Australians (P < .0001). The age-adjusted prevalence of self-reported
stroke for non-Indigenous and Indigenous Australians was 4.23% and 12.72%,
respectively. The prevalence of stroke increased significantly with age for both
Indigenous (odds ratio = 1.06 per year, P <= .001) and non-Indigenous Australians
(odds ratio = 1.04 per year, P <= .001), with the Indigenous prevalence being
higher than that of the non-Indigenous group at every age. CONCLUSIONS: The
prevalence of self-reported stroke was 3 times higher in Indigenous Australians
than in non-Indigenous Australians. This disparity is consistent with previous
reports, highlighting the need for intensified prevention and support services to
reduce the burden of stroke on Indigenous Australians.
PMID- 28411040
TI - Occurrence of hepatocellular carcinoma in HIV/HCV co-infected patients treated
with direct-acting antivirals.
PMID- 28411041
TI - In HIV/HCV co-infected patients T regulatory and myeloid-derived suppressor cells
persist after successful treatment with directly acting antivirals.
PMID- 28411042
TI - Negotiating better discounts for DAA therapy is critical to achieve HCV
elimination by 2030.
PMID- 28411043
TI - Gastrointestinal Hormone Cholecystokinin Increases P-Glycoprotein Membrane
Localization and Transport Activity in Caco-2 Cells.
AB - It was reported that stimulation of taste receptor type 2 member 38 by a bitter
substance, phenylthiocarbamide (PTC), increased P-glycoprotein (P-gp) mRNA level
and transport activity via release of the gastrointestinal hormone
cholecystokinin-8 (CCK-8) at 9 h. Therefore, we hypothesized that CCK-8 and PTC
might also regulate P-gp activity more rapidly via a different mechanism. As a
result, we found that the pretreatment of human colon adenocarcinoma (Caco-2)
cells with 10-mM PTC significantly decreased the intracellular accumulation of P
gp substrate rhodamine 123 (Rho123) compared with the control after 90-min
incubation. Moreover, CCK-8 treatments significantly reduced the accumulation of
Rho123 within 30 min, compared with the control. On the other hand, when Caco-2
cells were pretreated with PTC, the efflux ratio of Rho123 was significantly
increased compared with control. The efflux ratio of Rho123 in CCK-8 treatment
cells was also significantly increased compared with control. Furthermore, CCK-8
increased the phosphorylation of the scaffold proteins ezrin, radixin, and
moesin, which regulate translocation of P-gp to the plasma membrane. Therefore,
our results indicate that PTC induced release of CCK-8, which in turn induced the
phosphorylation of ezrin, radixin, and moesin proteins, leading to upregulation
of P-gp transport activity via increased membrane localization of P-gp.
PMID- 28411044
TI - A short report on the effect of decreased incubation time on the architectural
profile of autologous conditioned serum (ACS).
AB - If present in high enough concentrations, IL-1-Ra has the potential to inhibit
Interleukin-1, the chief offender that promotes the pro-inflammatory cascade
causing pain, swelling and joint dysfunction associated with osteoarthritis (OA).
IL-1-Ra and growth factor levels were quantified from whole blood in this
retrospective chart review investigation (n=20) using Zero and 15min incubation
times respectively. The hypothesis that this process can significantly (p<0.0001)
increase levels of IL-1-Ra was confirmed. Mean ArthrokinexTM induced IL-1-Ra
levels reached a concentration of 13,288pg/mL and 12,809pg/mL compared to
518pg/mL at baseline, representing a 26-fold increase. Post conditioning levels
of pro-inflammatories IL-1beta, IL-6 and TNF alpha were not changed to any
significant degree. The ArthrokinexTM blood conditioning process induces adequate
levels of IL-1-Ra to alter the IL-1-Ra: IL-1beta ratio and mitigate the
inflammatory cascade, while increasing growth factors PDGF and TGF respectively.
PMID- 28411045
TI - Pro-inflammatory effects of the Th1 chemokine CXCL10 in acquired aplastic
anaemia.
AB - CXCL10/IFN-gamma-induced protein 10 (IP-10) and its corresponding receptor CXCR3
have long been considered to be involved in the pathophysiology of type 1 T (Th1)
cell-orientated autoimmune diseases. However, the exact role of CXCL10 in the
pathogenesis of aplastic anaemia (AA) has not been thoroughly studied. The aim of
our study was to evaluate the plasma level of CXCL10 and its effects on CD4+ T
cell differentiation in AA. In our study, we found that an elevated plasma level
of CXCL10 was negatively correlated with platelet, absolute neutrophil and
reticulocyte counts, while it was positively correlated with the proportion of
lymphocytes in white blood cells in AA patients. To confirm the pro-inflammatory
effects of CXCL10 in AA, we isolated CD4+ T cells and evaluated the function of
CXCL10 in CD4+ T cell differentiation. In vitro stimulation experiments further
revealed the pro-inflammatory role of CXCL10 in AA, partially by promoting the
secretion of interferon (IFN)-gamma and IL-17. In addition, CXCL10 significantly
skewed CD4+ T cell differentiation to Th1 cells and T helper 17 (Th17) cells in
AA patients, while it inhibited the differentiation of type 2 T (Th2) cells only
in controls. The mRNA expression of transcription factors representative of T
cell differentiation was detected by RT-PCR. Consistently, our results showed
that after CXCL10 treatment, the expression of T-bet and RORgammat was
significantly enhanced, while the expression of GATA3 was inhibited. In
conclusion, our results indicated that CXCL10, a pro-inflammatory chemokine,
might be involved in the abnormal immune response in AA.
PMID- 28411046
TI - Different influence of antipsychotics on the balance between pro- and anti
inflammatory cytokines depends on glia activation: An in vitro study.
AB - The microglial hypothesis of schizophrenia suggests that its neuropathology is
closely associated with neuroinflammation manifested, inter alia, by an increased
expression of cytokines. However, clinical investigations imply that
schizophrenia is a heterogeneous disease and in some groups of patients the
activated inflammatory process does not contribute to the disease-associated
impairment of brain function. Clinical studies revealed also an equivocal impact
of antipsychotics on peripheral and CSF cytokines, whereas experimental research
performed on the stimulated glia cultures showed their inhibitory effect on pro
inflammatory cytokine levels. In the present study, the effect of chlorpromazine,
haloperidol and risperidone (0.5, 5 or 10MUM) on production of pro-inflammatory
cytokines IL-1beta and TNF-alpha and anti-inflammatory IL-10 was investigated in
the unstimulated and lipopolysaccharide-stimulated primary rat mixed glial cell
cultures. In the unstimulated cultures, haloperidol at all applied
concentrations, risperidone at 5, 10MUM and chlorpromazine at 10MUM increased IL
10 levels in the culture supernatants without a significant influence on IL-1beta
or TNF-alpha levels, and all drugs applied at 10MUM induced a robust increase in
IL-10 mRNA expression. Under strong inflammatory activation, haloperidol and
risperidone at all concentrations reduced production of both pro-inflammatory
cytokines, without adverse effects on IL-10 expression when used at 10MUM.
Chlorpromazine at all concentrations diminished the production of three cytokines
and did not induce anti-inflammatory effect. These results suggest that
dependently on glia activation antipsychotics via different mechanisms may induce
anti-inflammatory effect and that this activity is not common for all drugs under
conditions of strong glia activation.
PMID- 28411047
TI - Immunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac
surgery - A prospective trial.
AB - BACKGROUND: Corrective surgery for congenital heart defects is known to trigger a
severe immune reaction. There has been extensive research on the effects of
inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are
observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under
these conditions, indicating a state of immunodepression, which lays the ground
for second hit infections after cardiosurgery with CPB. OBJECTIVES: The aim of
this prospective study was to analyze immunodepression after pediatric
cardiopulmonary bypass and to differentiate the effects of monocytic anergy on
postoperative outcome. METHODS: In a prospective trial, we quantified the immune
responses in 20 pediatric patients (median age 4.9months, range 2.3-38.2months;
median weight 7.2kg, range 5.2-11.7kg) with congenital ventricular septal defect
undergoing heart surgery with CPB. Ex vivo LPS-induced protein expression of IFN
gamma, IL-1beta, IL-1Ra, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-alpha, and MCP-1
was measured before (T1), immediately after (T2) and 4h after (T3)
cardiopulmonary bypass surgery using Luminex technology. RESULTS: The innate
immune system responds to CPB with an almost complete depression of monocytic
function. Inflammatory IL-12, TNF-alpha, IL-1beta, IL-6, IL-8 and IFN-y are
completely suppressed. IL-10, IL-1Ra and MCP-1 are still produced during
suppression with IL-1Ra being overly secreted during reversion. Suppression of
TNF-alpha expression after LPS-stimulation correlates closely with longer
mechanical ventilation time (r=-0.619, p=0.004). CONCLUSION: Cardiosurgery with
CPB causes a state of immunodepression making pediatric patients more vulnerable
to second hit infections. MCP-1, IL-10, and IL-1Ra play an important role in
monocyte recovery, eventually permitting new therapeutic options for controlling
immunodepression and inflammation. Standardized glucocorticoid therapy should be
evaluated carefully for each individual patient.
PMID- 28411048
TI - Development of cellulase-nanoconjugates with enhanced ionic liquid and thermal
stability for in situ lignocellulose saccharification.
AB - The present work aimed to improve catalytic efficiency of Trichoderma reesei
cellulase for enhanced saccharification. The cellulase was immobilized on two
nanomatrices i.e. magnetic and silica nanoparticles with immobilization
efficiency of 85% and 76% respectively. The nanobioconjugates exhibited increase
in Vmax, temperature optimum, pH and thermal stability as compared with free
enzyme. These could be efficiently reused for five repeated cycles and were
stable in 1-ethyl-3-methylimidazoliumacetate [EMIM][Ac], an ionic liquid. Ionic
liquids (IL) are used as green solvents to dissolve lignocellulosic biomass and
facilitate better saccharification. The cellulase immobilized on magnetic
nanoparticles was used for in situ saccharification of [EMIM][Ac] pretreated
sugarcane bagasse and wheat straw for two cycles. The structural deconstruction
and decrease in biomass crystallinity was confirmed by SEM, XRD and FTIR. The
high hydrolysis yields (~89%) obtained in this one-pot process coupled with IL
stability and recycled use of immobilized cellulase, potentiates its usefulness
in biorefineries.
PMID- 28411049
TI - Impact of ultrasounds and high voltage electrical discharges on physico-chemical
properties of rapeseed straw's lignin and pulps.
AB - In this study, ultrasound (US) and high voltage electrical discharges (HVED) were
combined with chemical treatments (soda or organosolv) for rapeseed straw
delignification. Delignification was improved by both physical pretreatments. US
increased the extractability of hemicelluloses and HVED induced a partial
degradation of cellulose. Best synergies were observed for HVED-soda and US
organosolv treatments. The obtained lignin fractions were characterized with 13C
NMR and 2D 1H-13C HSQC. It was observed that the physical treatments affected the
syringyl/guaiacyl (S/G) ratios. The values of S/G were ~1.19, 1.31 and 1.75 for
organosolv, HVED-organosolv and US-organosolv processes, suggesting
recondensation reactions. The lignin fractions obtained from HVED-organosolv
treatment contained less quantity of p-coumaric acid and ferulic acid as compared
to those extracted by US-organosolv. Thermogravimetric analysis (TGA) revealed a
better heat resistance of physically extracted lignins as compared to the
control. The enzymatic digestibility increased by 24.92% when applying HVED to
mild organosolv treatment.
PMID- 28411050
TI - Impact of wet aerobic pretreatments on cellulose accessibility and bacterial
communities in rape straw.
AB - A new pretreatment method of lignocellulosic biomass was explored by using a wet
aerobic process with an alkaline lignin and a mineral salt solution. This
treatment significantly improved structural modification of rape straw used as
substrate model in this study. Change in cellulose accessibility to cellulase of
rape straw rose up to six fold within the first days of this pretreatment without
generated significant modification of van Soest lignocellulose fractionation. The
biological pretreatment apply to rape straw induced a high microbial activity
revealed by quantitative PCR and sequencing techniques, suggesting that bacteria
including Xanthomonadales and Sphingobacteriales may be involved in this
lignocellulosic biomass transformation. Moreover, results of this work
demonstrate that the endogenous microbial community associated with rape straw
plays a key role in its alteration.
PMID- 28411051
TI - Enhancing enzymatic hydrolysis of coconut husk through Pseudomonas aeruginosa AP
029/GLVIIA rhamnolipid preparation.
AB - This work investigated the influence of chemical (Triton X-100) and biological
surfactant preparation (rhamnolipids) in coconut husk hydrolysis that was
subjected to pretreatment with acid-alkali or alkaline hydrogen peroxide. The
natural and pretreated biomass was characterized using the National Renewable
Energy Laboratory protocol analysis as well as X-ray diffraction and scanning
electron microscopy. The results demonstrated that in terms of the total reducing
sugars, there was no significant difference between the hydrolysis using Triton X
100 and rhamnolipids, regardless of the pretreatment. A cellulosic conversion
value as high as 33.0% was obtained in experiments with rhamnolipids. The coconut
husk was observed to be a potential biomass that could produce second generation
ethanol, and the rhamnolipid preparation can be used to support for the enzymatic
hydrolysis, enhancing the advantage of cellulose conversion into glucose over
chemical surfactants because it is an environmentally friendly approach.
PMID- 28411052
TI - Selective enrichment of Eicosapentaenoic acid (20:5n-3) in N. oceanica CASA CC201
by natural auxin supplementation.
AB - The present study aims to evaluate the effect of different concentration of
natural auxin, Indole-3 acetic acid (IAA) on growth, lipid yield, PUFA and EPA
accumulation in Nannochloropsis oceanica CASA CC201. It was observed that the,
treatment with 10ppm concentration of IAA resulted in high cell number
579.5*106cells/ml than the control (215.5*106cells/ml). Treatment with IAA at a
concentration of 40ppm gives the highest cellular lipid accumulation of 60.9% DCW
than the control 31.05% DCW). Lipid yield is also found to be increased by the
addition of 40ppm IAA (319.5mg/L) compared with the control (121.5mg/L). EPA
percentage is increased to 10.76% by the addition of 40ppm IAA compared to the
control (1.87%).
PMID- 28411053
TI - Fostering triacylglycerol accumulation in novel oleaginous yeast Cryptococcus
psychrotolerans IITRFD utilizing groundnut shell for improved biodiesel
production.
AB - The investigation was carried out to examine the potential of triacylglycerol
(TAG) accumulation by novel oleaginous yeast isolate Cryptococcus psychrotolerans
IITRFD on utilizing groundnut shell acid hydrolysate (GSH) as cost-effective
medium. The maximum biomass productivity and lipid productivity of 0.095+/
0.008g/L/h and 0.044+/-0.005g/L/h, respectively with lipid content 46% was
recorded on GSH. Fatty acid methyl ester (FAME) profile obtained by GC-MS
analysis revealed oleic acid (37.8%), palmitic (29.4%) and linoleic (32.8%) as
major fatty acids representing balance between oxidative stability (OS) and cold
flow filter properties (CFFP) for improved biodiesel quality. The biodiesel
property calculated were correlated well with the fuel standards limits of ASTM
D6751, EN 14214 and IS 15607. The present findings raise the possibility of using
agricultural waste groundnut shell as a substrate for production of biodiesel by
novel oleaginous yeast isolate C. psychrotolerans IITRFD.
PMID- 28411054
TI - Salidroside protects rat liver against ischemia/reperfusion injury by regulating
the GSK-3beta/Nrf2-dependent antioxidant response and mitochondrial permeability
transition.
AB - Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and
neuroprotective effects in vivo and in vitro; however, its impact on hepatic
ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was
to investigate the hepatoprotective effects of salidroside against segmental
(70%) warm hepatic I/R injury in rats. Animals were randomized into Sham,
Sham+salidroside pretreatment (Sal), Sham+Sal+carboxyatractyloside (CATR),
Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups. The hepatic artery,
left portal vein and median liver lobes were occluded for 60min and then
unclamped to allow reperfusion. Pretreatment with salidroside (20mg/kg/day for 7
days, intraperitoneally) significantly decreased serum alanine aminotransferase
(sALT) and serum aspartate aminotransferase (sAST) levels after 6h and 24h of
reperfusion and protected the liver against I/R-induced injury. However, this
protective effect could be reversed by CATR, a mitochondrial permeability
transition pore (MPTP) opener (5mg/kg 30min before I/R insult,
intraperitoneally). Mechanistic studies have revealed that salidroside inhibits
glycogen synthase kinase-3 beta (GSK-3beta) activity and enhances the NF-E2
related factor (Nrf2)-dependent antioxidant response by activating the Akt
signaling pathway, thereby reducing mitochondrial reactive oxygen species
generation, increasing MPTP resistance and preventing apoptosis by suppressing
cytochrome c release and caspase activation during reperfusion. Therefore,
salidroside ameliorates hepatocyte death and apoptosis through activation of the
GSK-3beta/Nrf2-dependent antioxidant response and subsequent MPTP inhibition.
These results provide experimental evidence supporting the clinical use of
salidroside for hepatoprotection in surgical settings.
PMID- 28411055
TI - PPARalpha, PPARgamma and SREBP-1 pathways mediated waterborne iron (Fe)-induced
reduction in hepatic lipid deposition of javelin goby Synechogobius hasta.
AB - The 42-day experiment was conducted to investigate the effects and mechanism of
waterborne Fe exposure influencing hepatic lipid deposition in Synechogobius
hasta. For that purpose, S. hasta were exposed to four Fe concentrations (0
(control), 0.36, 0.72 and 1.07MUM Fe) for 42days. On days 21 and 42,
morphological parameters, hepatic lipid deposition and Fe contents, and
activities and mRNA levels of enzymes and genes related to lipid metabolism,
including lipogenic enzymes (6PGD, G6PD, ME, ICDH, FAS and ACC) and lipolytic
enzymes (CPTI, HSL), were analyzed. With the increase of Fe concentration,
hepatic Fe content tended to increase but HSI and lipid content tended to
decrease. On day 21, Fe exposure down-regulated the lipogenic activities of 6PGD,
G6PD, ICDH and FAS as well as the mRNA levels of G6PD, ACCa, FAS, SREBP-1 and
PPARgamma, but up-regulated CPT I, HSLa and PPARalpha mRNA levels. On day 42, Fe
exposure down-regulated the lipogenic activities of 6PGD, G6PD, ICDH and FAS as
well as the mRNA levels of 6PGD, ACCa, FAS and SREBP-1, but up-regulated CPT I,
HSLa, PPARalpha and PPARgamma mRNA levels. Using primary S. hasta hepatocytes,
specific pathway inhibitors (GW6471 for PPARalpha and fatostatin for SREBP-1) and
activator (troglitazone for PPARgamma) were used to explore the signaling
pathways of Fe reducing lipid deposition. The GW6471 attenuated the Fe-induced
down-regulation of mRNA levels of 6PGD, G6PD, ME, FAS and ACCa, and attenuated
the Fe-induced up-regulation of mRNA levels of CPT I, HSLa and PPARalpha.
Compared with single Fe-incubated group, the mRNA levels of G6PD, ME, FAS, ACCa,
ACCb and PPARgamma were up-regulated while the CPT I mRNA levels were down
regulated after troglitazone pre-treatment; fatostatin pre-treatment down
regulated the mRNA levels of 6PGD, ME, FAS, ACCa, ACCb and SREBP-1, and increased
the CPT I and HSLa mRNA levels. Based on these results above, our study indicated
that Fe exposure reduced hepatic lipid deposition by down-regulating lipogenesis
and up-regulating lipolysis, and PPARalpha, PPARgamma and SREBP-1 pathways
mediated the Fe-induced reduction of hepatic lipid deposition in S. hasta.
PMID- 28411056
TI - Development and evaluation of resveratrol, Vitamin E, and epigallocatechin
gallate loaded lipid nanoparticles for skin care applications.
AB - Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been
studied as potential carriers for both dermal and transdermal drug delivery. SLN
contain lipid droplets that are fully crystallized and have a highly-ordered
crystalline structure. NLC are modified SLN in which the lipid phase contains
both solid and liquid lipids at room temperature. SLN and NLC are thought to
combine the advantages of polymeric particles, liposomes and emulsions. Therefore
they provide high encapsulation percentages, better protection for incorporated
actives and allow for control of desired release profile. In this work,
Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent
antioxidants known to provide protection to the skin, were formulated into lipid
nanoparticles. Several different formulations were successfully developed and
demonstrated high uniformity and stability. Both resveratrol and VE lipid
nanoparticles provided effective protection of actives against UV induced
degradation. However, lipid nanoparticles did not show protection from UV
degradation for EGCG in this work. An active release study exhibited a sustained
release of resveratrol over 70% after 24h. Skin penetration studies showed that
lipid nanoparticles directionally improved the penetration of resveratrol through
the stratum corneum. Our findings suggest that lipid nanoparticles are promising
viable carriers for the delivery of resveratrol and VE to provide longlasting
antioxidant benefits to the skin.
PMID- 28411058
TI - Brain signatures of early lexical and morphological learning of a new language.
AB - Morphology is an important part of language processing but little is known about
how adult second language learners acquire morphological rules. Using a word
picture associative learning task, we have previously shown that a brief exposure
to novel words with embedded morphological structure (suffix for natural gender)
is enough for language learners to acquire the hidden morphological rule. Here we
used this paradigm to study the brain signatures of early morphological learning
in a novel language in adults. Behavioural measures indicated successful lexical
(word stem) and morphological (gender suffix) learning. A day after the learning
phase, event-related brain potentials registered during a recognition memory task
revealed enhanced N400 and P600 components for stem and suffix violations,
respectively. An additional effect observed with combined suffix and stem
violations was an enhancement of an early N2 component, most probably related to
conflict-detection processes. Successful morphological learning was also evident
in the ERP responses to the subsequent rule-generalization task with new stems,
where violation of the morphological rule was associated with an early (250
400ms) and late positivity (750-900ms). Overall, these findings tend to converge
with lexical and morphosyntactic violation effects observed in L1 processing,
suggesting that even after a short exposure, adult language learners can acquire
both novel words and novel morphological rules.
PMID- 28411057
TI - Microwave-assisted microemulsion technique for production of miconazole nitrate-
and econazole nitrate-loaded solid lipid nanoparticles.
AB - The microwave-assisted production of solid lipid nanoparticles (SLNs) is a novel
technique reported recently by our group. The small particle size, solid nature
and use of physiologically well-tolerated lipid materials make SLNs an
interesting and potentially efficacious drug carrier. The main purpose of this
research work was to investigate the suitability of microwave-assisted
microemulsion technique to encapsulate selected ionic drug substances such as
miconazole nitrate and econazole nitrate. The microwave-produced SLNs had a small
size (250-300nm), low polydispersity (<0.20), high encapsulation efficiency (72
87%) and loading capacity (3.6-4.3%). Differential scanning calorimetry (DSC) and
X-ray diffraction (XRD) studies suggested reduced crystallinity of stearic acid
in SLNs. The release studies demonstrated a slow, sustained but incomplete
release of drugs (<60% after 24h) from microwave-produced SLNs. Data fitting of
drug release data revealed that the release of both drugs from microwave-produced
SLNs was governed by non-Fickian diffusion indicating that drug release was both
diffusion- and dissolution- controlled. Anti-fungal efficacy of drug-loaded SLNs
was evaluated on C. albicans. The cell viability studies showed that cytotoxicity
of SLNs was concentration-dependent. These encouraging results suggest that the
microwave-assisted procedure is suitable for encapsulation of ionic drugs and
that microwave-produced SLNs can act as potential carriers of antifungal drugs.
PMID- 28411059
TI - Antibacterial efficacy of silver nanoparticles against multi-drug resistant
clinical isolates from post-surgical wound infections.
AB - In order to investigate new effective and inexpensive nano-therapeutic approach
for P. aeruginosa, staphylococcus aureus and coagulase negative staphylococci
(CoNS), the present study reports an eco-friendly process for rapid synthesis of
silver nanoparticles (Ag-NPs) using aqueous leaf extract of Corchorus Capsularis
(CRCP). Formation of stable Ag-NPs at different time intervals gives mostly
spherical particles with diameters ranging from 5 to 45 nm. The resulting Ag-NPs
were characterized using Ultraviolet visible (UV-Vis) spectroscopy, Fourier
Transform Infrared (FT-IR) spectroscopy, X-Ray Diffraction (XRD) analysis,
Transmission Electron Microscopy (TEM) and Energy Dispersive X-ray analysis
(EDX). XRD study shows that the particles are crystalline in nature with face
centered cubic geometry. TEM studies show the formation of Ag-NPs with average
size of 20.52 nm. The antimicrobial activity of the synthesized Ag-NPs was
investigated against multi drug resistant (MDR) P. aeruginosa, Staphylococcus
aureus and CoNS isolates from post-surgical wound infections. The present study
suggests that Ag-NPs synthesized from aqueous leaf extract of CRCP shows
significant antibacterial potential against MDR isolates from post-surgical wound
infections.
PMID- 28411060
TI - In vitro anti-Candida activity of selective serotonin reuptake inhibitors against
fluconazole-resistant strains and their activity against biofilm-forming
isolates.
AB - Recent research has shown broad antifungal activity of the classic
antidepressants selective serotonin reuptake inhibitors (SSRIs). This fact,
combined with the increased cross-resistance frequency of the genre Candida
regarding the main treatment today, fluconazole, requires the development of
novel therapeutic strategies. In that context, this study aimed to assess the
antifungal potential of fluoxetine, sertraline, and paroxetine against
fluconazole-resistant Candida spp. planktonic cells, as well as to assess the
mechanism of action and the viability of biofilms treated with fluoxetine. After
24 h, the fluconazole-resistant Candida spp. strains showed minimum inhibitory
concentration (MIC) in the ranges of 20-160 MUg/mL for fluoxetine, 10-20 MUg/mL
for sertraline, and 10-100.8 MUg/mL for paroxetine by the broth microdilution
method (M27-A3). According to our data by flow cytometry, each of the SSRIs cause
fungal death after damaging the plasma and mitochondrial membrane, which
activates apoptotic signaling pathways and leads to dose-dependant cell viability
loss. Regarding biofilm-forming isolates, the fluoxetine reduce mature biofilm of
all the species tested. Therefore, it is concluded that SSRIs are capable of
inhibit the growth in vitro of Candida spp., both in planktonic form, as biofilm,
inducing cellular death by apoptosis.
PMID- 28411061
TI - A nuanced view of post-anoxic myoclonus.
PMID- 28411062
TI - Incidence and characteristics of positive pressure ventilation delivered to
newborns in a US tertiary academic hospital.
AB - INTRODUCTION: The Neonatal Resuscitation Program (NRP) guidelines recommend
positive pressure ventilation (PPV) in the first 60s of life to support perinatal
transition in non-breathing newborns. Our aim was to describe the incidence and
characteristics of newborn PPV using real-time observation in the delivery unit.
METHODS: Prospective, observational, quality improvement study conducted at a
tertiary academic hospital. Deliveries during randomized weekday/evening 8-h
shifts were attended by a trained observer. Intervention data were recorded for
all newborns with gestational age (GA) >=34wks that received PPV. Descriptive
summaries and Kruskal-Wallis test for continuous variables and Fisher's exact
test for categorical variables were used to compare characteristics. RESULTS: Of
1135 live deliveries directly observed over 18mos, 64 (6%) newborns with a mean
GA 39+/-2wks received PPV: Median time from birth to warmer was 20s (IQR 15-22s);
PPV was initiated within 60s of life in 29 (45%) and between 60 and 90s of life
in 17 (27%). PPV duration was <120s in 38 (60%). Seven/21 (33%) newborns that
received PPV after vaginal delivery were not pre-identified and resuscitation
team was alerted after delivery. We found no association between PPV start time
and duration of PPV (p=0.86). CONCLUSION: We observed that most (94%) term
newborns spontaneously initiate respirations. In over half observed deliveries
receiving PPV, time to initiation of PPV was greater than 60s (longer than
recommended). Compliance with current NRP guidelines is difficult, and it's not
clear whether it is the recommendations or the training to achieve PPV
recommendations that should be modified.
PMID- 28411064
TI - Health benefits of a reduction of PM10 and NO2 exposure after implementing a
clean air plan in the Agglomeration Lausanne-Morges.
AB - Exposure to urban air pollution has been associated with adverse effects on
cardio-vascular and respiratory health, both short and long term. Consequently,
governments have applied policies to reduce air pollution. Quantitative health
impact assessments of hypothetic changes in air pollution have been conducted at
national and global level, but assessments of observed air pollution changes
associated with specific clean air policies at a local or regional scale remain
scarce. This study estimates health impacts attributable to a decrease in PM10
and NO2 exposure in the Agglomeration of Lausanne-Morges (ALM), Switzerland,
between 2005 and 2015, corresponding to the implementation period of a supra
municipal plan of measures to reduce air pollution in different sectors such as
transport, energy, and industry (called Plan OPair 05). The health impact
assessment compares health effects attributed to air pollution exposure levels in
2015 (reference case) with those in 2005 (counterfactual scenario), using 2015 as
baseline for all other input data. In the ALM, the modeled PM10 exposure
reduction of 3.3MUg/m3 from 2005 to 2015 prevents 26 premature deaths (equivalent
to around 290 years of life lost), 215 hospitalization days due to cardio
vascular and respiratory diseases as well as approximately 47,000 restricted
activity days annually. Monetized health impacts of the reduction of PM10
exposure are valued at approximately CHF 36 million annually. Immaterial costs,
mainly related to the economic valuation of years of life lost, dominate the
monetized health impacts (90% of total value), while savings at the workplace
(net loss in production and reoccupation costs) amount to about CHF 1.9 million,
and savings in health care costs to about CHF 0.5 million. The assessment is
sensitive to the value assigned to immaterial costs and to uncertainties in the
relative risk estimates, whereas variations in the baseline year (i.e. using 2005
data instead of 2015 data) affect results to a much lower degree. The alternative
calculation based on NO2 exposure, which dropped by 5.6MUg/m3, suggests the
prevention of 51 premature deaths (equivalent to around 550 years of life lost)
overall impacts valued at CHF 49 million. All in all, the reduction in mortality
due to the air quality improvements accounts for (depending on the considered
pollutant) about 1% to 2% of total all-cause annual mortality in the ALM
population or 4-8 times larger than the annual traffic fatalities in the ALM.
PMID- 28411063
TI - Deploying dengue-suppressing Wolbachia : Robust models predict slow but effective
spatial spread in Aedes aegypti.
AB - A novel strategy for controlling the spread of arboviral diseases such as dengue,
Zika and chikungunya is to transform mosquito populations with virus-suppressing
Wolbachia. In general, Wolbachia transinfected into mosquitoes induce fitness
costs through lower viability or fecundity. These maternally inherited bacteria
also produce a frequency-dependent advantage for infected females by inducing
cytoplasmic incompatibility (CI), which kills the embryos produced by uninfected
females mated to infected males. These competing effects, a frequency-dependent
advantage and frequency-independent costs, produce bistable Wolbachia frequency
dynamics. Above a threshold frequency, denoted p^, CI drives fitness-decreasing
Wolbachia transinfections through local populations; but below p^, infection
frequencies tend to decline to zero. If p^ is not too high, CI also drives
spatial spread once infections become established over sufficiently large areas.
We illustrate how simple models provide testable predictions concerning the
spatial and temporal dynamics of Wolbachia introductions, focusing on rate of
spatial spread, the shape of spreading waves, and the conditions for initiating
spread from local introductions. First, we consider the robustness of diffusion
based predictions to incorporating two important features of wMel-Aedes aegypti
biology that may be inconsistent with the diffusion approximations, namely fast
local dynamics induced by complete CI (i.e., all embryos produced from
incompatible crosses die) and long-tailed, non-Gaussian dispersal. With complete
CI, our numerical analyses show that long-tailed dispersal changes wave-width
predictions only slightly; but it can significantly reduce wave speed relative to
the diffusion prediction; it also allows smaller local introductions to initiate
spatial spread. Second, we use approximations for p^ and dispersal distances to
predict the outcome of 2013 releases of wMel-infected Aedes aegypti in Cairns,
Australia, Third, we describe new data from Ae. aegypti populations near Cairns,
Australia that demonstrate long-distance dispersal and provide an approximate
lower bound on p^ for wMel in northeastern Australia. Finally, we apply our
analyses to produce operational guidelines for efficient transformation of vector
populations over large areas. We demonstrate that even very slow spatial spread,
on the order of 10-20 m/month (as predicted), can produce area-wide population
transformation within a few years following initial releases covering about 20
30% of the target area.
PMID- 28411065
TI - Modifying the physicochemical properties of pea protein by pH-shifting and
ultrasound combined treatments.
AB - The effect of a pH-shifting and ultrasound combined process on the functional
properties and structure of pea protein isolate (PPI) was investigated. PPI
dispersions were adjusted to pH 2, 4, 10, or 12, treated by power ultrasound for
5min, and incubated for 1h before the sample pH was brought back to neutral.
After treatment, water solubility, protein aggregate size, solution turbidity,
surface hydrophobicity (Ho), free sulfhydryl content (SH), and sodium dodecyl
sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the soluble PPI were
determined. pH-shifting at pH 12 and ultrasound combined treatment (pH12-US)
significantly improved protein properties, while property modification of the
samples treated under acidic conditions was less pronounced. The pH12-US treated
PPI had a solubility seven times higher than the control, reaching an average
particle size of 45.2nm. In addition, the pH12-US treated PPI significantly
improved Ho due to disulfide bonds disruption, and produced more protein sub
units than other treatments. The soluble PPI obtained through this process may be
a promising emulsifier for the enrichment of fat-soluble nutrients in foods.
PMID- 28411066
TI - The Actual and Ideal Sexual Self Concept in the Context of Genital Pain Using
Implicit and Explicit Measures.
AB - BACKGROUND: The experience of pain during sexual intercourse generates
significant distress and sexual impairments, which is likely to affect sexual
identity and become a threat to the sense of self. AIM: To explore the role of
the concept of the sexual self in the context of genital pain by measuring
different states of self (ie, actual vs ideal) at different levels of responding
(ie, explicit vs implicit) and examine their associations with sexual, emotional,
and pain-related variables. METHODS AND MAIN OUTCOMES: Thirty young women who
identified with genital pain and 29 women without pain completed (i) two versions
of the Relational Responding Task as a measurement of implicit actual and ideal
sexual self; (ii) explicit ratings of the actual and the ideal sexual self; and
(iii) measurements of sexual self-esteem, global self-esteem, depression, sexual
satisfaction, sexual distress or depression, sexual frequency, and pain
experiences. RESULTS: Women with genital pain scored lower on the explicit and
implicit actual-self measurements than women without pain but did not differ in
their ideal self. Furthermore, the pain group reported higher ideal- than actual
self scores at the explicit level. Actual- and ideal-self measurements had
differential effects on sexual, emotional, and behavioral outcome variables. In
general, rating the ideal self higher than the actual self was related to more
negative outcomes. Pain-related variables were predicted only by the implicit
measurements, showing that the high pain group reported more pain, fear of pain,
and a stronger tendency to continue with sex despite the pain when perceiving
themselves as sexually less competent and when this perception did not match
their ideal self. CLINICAL IMPLICATIONS: Therapeutic interventions might benefit
from discussing women's internal guides for self, decreasing potential
discrepancies, and developing identity-related motivational treatments that
target the emotional discomfort and maladaptive behavioral strategies that result
from trying to conform with their guides of self. Setting idealistically high
sexual standards, feeling pressure to perform as a sexual partner, and fearing to
be sexually unqualified could be key factors in developing, maintaining, and
exacerbating sexual dysfunctions. STRENGTHS AND LIMITATIONS: This is the first
study to systematically examine different components of the concept of the sexual
self in the context of genital pain. Despite the small sample and the use of a
non-clinical group of women, we found a theoretically and clinically interesting
pattern of results. CONCLUSIONS: Differentiating between different components of
the sexual self is relevant to explain sexual, emotional, and pain-related
responses. Dewitte M, De Schryver M, Heider N, De Houwer J. The Actual and Ideal
Sexual Self Concept in the Context of Genital Pain Using Implicit and Explicit
Measures. J Sex Med 2017;14:702-714.
PMID- 28411067
TI - Is Cigarette and Alcohol Use Associated With High-Risk Sexual Behaviors Among
Youth in China?
AB - BACKGROUND: Very few studies have explored the association between cigarette or
alcohol use and high-risk sexual behaviors (HRSBs) among Chinese youth. AIM: To
identify the associations between cigarette and/or alcohol use and HRSBs in
unmarried youth 15 to 24 years old in China. METHODS: Data were obtained from a
nationally representative survey of youth 15 to 24 years old in China. Population
numbers, prevalences, and proportions were calculated where appropriate. The chi2
test was used to examine the different proportions of cigarette and alcohol use
behaviors and HRSBs in female vs male youth. Logistic regression with propensity
score-based weighting was used to elucidate the separate and combined
associations of cigarette use and alcohol use with each HRSB. OUTCOMES: The
sexual behaviors of condom non-use during the first sexual experience, sexual
activity with multiple partners, being forced to have sexual intercourse, taking
part in casual sex, engaging in commercial sex, taking part in anal sex, and
condom non-use during the most recent sexual encounter were classified as HRSBs.
RESULTS: Of youth 15 to 24 years old, 23.2% ever used cigarettes, 38.1% used
alcohol, and 19.9% used cigarettes and alcohol. Compared with cigarette and
alcohol non-use, cigarette and alcohol use showed a significantly increased risk
of condom non-use during the first sexual experience (odds ratio = 2.9, 95% CI =
2.5-3.3), sexual activity with multiple partners (4.9, 3.8-6.2), forced sex (2.7,
1.1-6.9), casual sex (4.0, 3.1-5.3), commercial sex (2.9, 2.1-3.9), anal
copulation (3.1, 2.1-4.6), condom non-use during the most recent sexual encounter
(2.5, 2.1-3.0), and any HSRB (3.2, 2.8-3.6) among youth. The relations between
cigarette and alcohol use and HRSBs were stronger among female youth than among
male youth for all HRSBs. CLINICAL IMPLICATIONS: More efforts should be made to
implement HIV and AIDS prevention that consider the role of cigarette and alcohol
use in precipitating HRSBs. STRENGTHS AND LIMITATIONS: This study provided a more
detailed evaluation with greater confidence of the association between cigarette
and/or alcohol use and HRSBs with sex disparity taken into account using
nationally representative data, although no detailed information about cigarette
and alcohol use behaviors such as dependence and cessation was gathered in this
survey. CONCLUSION: Youth who use cigarette and alcohol are at greater risk of
HRSBs, especially female youth. Guo C, Wen X, Li N, et al. Is Cigarette and
Alcohol Use Associated With High-Risk Sexual Behaviors Among Youth in China? J
Sex Med 2017:14:659-665.
PMID- 28411068
TI - Protective effect of dapsone on cognitive impairment induced by propofol involves
hippocampal autophagy.
AB - Post-operative cognitive dysfunction (POCD) is a commonly seen postoperative
complication in elderly patients and its underlying mechanisms are still unclear.
Autophagy, a degradation mechanism of cellular components, is required for cell
survival and many physiological processes. Although propofol is one of the most
commonly used intravenous anesthetics, investigations into its mechanisms and
effects on cognition in aged rodents are relatively scarce. In this study, we
evaluate the influence of propofol on learning and memory, and identify the
potential role of hippocampal autophagy in propofol-induced cognitive alterations
in aged rats. The results demonstrate that 4h propofol exposure significantly
impaired cognitive performance through the inhibition of hippocampal autophagy.
Diaminodiphenyl sulfone (dapsone, DDS), which was used as an anti-leprosy drug,
has been found to have neuroprotective effects. We have previously demonstrated
that DDS can improve surgical stress induced depression- and anxiety-like
behavior. We therefore aimed to investigate the effects of DDS on propofol
induced cognitive dysfunction and associated hippocampal autophagy responses.
Pretreatment with 5mg/kg or 10mg/kg body weight DDS significantly improved the
behavioral disorder and upregulated the inhibited autophagic response in aged
rats. Our exploration is the first to establish an in vivo link between central
autophagy and cognitive dysfunction in aged hippocampus after propofol anesthesia
and demonstrate that the prophylactic effect of DDS on the cognitive impairment
induced by propofol involves autophagy. These findings may imply a potential
novel target for the treatment in patients with propofol anesthesia-induced
cognitive impairment.
PMID- 28411069
TI - Clostridium difficile and cystic fibrosis: management strategies and the role of
faecal transplantation.
AB - Clostridium difficile is a bacterial infection that colonises the gut in
susceptible hosts. It is associated with exposure to healthcare settings and
antibiotic use. It could be assumed that cystic fibrosis (CF) patients are a high
risk group for C.difficile. However, despite high carriage rates, CF patients
have low rates of active disease. There are guidelines for the treatment of
C.difficile, however little is published specific to treating C.difficile in CF.
This article provides an overview of the current management strategies for
C.difficile in CF, including a description of the first faecal transplantation in
this patient population.
PMID- 28411070
TI - Development and Initial Testing of the FLOW Instrument: Novel Assessment of Lower
Urinary Tract Symptoms in Men.
AB - PURPOSE: We sought to develop a method to assess lower urinary tract symptoms
regardless of literacy and numeracy. MATERIALS AND METHODS: We convened focus
groups and developed a questionnaire based on 4 identified domains of urinary
function, including frequency, incontinence (leakage), nocturia (overnight
voiding) and weak stream. We pilot tested the novel FLOW (frequency, leakage,
overnight voiding and weak stream) questionnaire in 64 men and performed
quantitative analysis to determine internal consistency. Criterion validity was
established via direct comparison to the AUA (American Urological Association)
symptom score in a larger cohort of 161 men. RESULTS: Median time to complete the
FLOW questionnaire was 18.0 seconds (IQR 15.8-21.0). The mean number of positive
responses to the FLOW instrument was 1.7. Test-retest reliability was 0.91 and
the Cronbach alpha was 0.67. In the validation cohort there was a significant
correlation between FLOW scores and AUA symptom score (r = 0.63, p <0.001). All
men regardless of health literacy completed FLOW. However, fewer men with low
health literacy completed the AUA symptom score compared to men with adequate
health literacy (81% vs 100%, p <0.001). For FLOW health literacy was unrelated
to the median completion time (21.5 seconds), the median number of prompts needed
(0) or the median score (2). CONCLUSIONS: A critical analysis of the AUA symptom
score using valid health literacy scales revealed that it is frequently not
completed, requires prompting and takes longer to complete for men with low
health literacy. The FLOW instrument represents a novel method to assess lower
urinary tract symptoms in all men. It represents a valid alternative to the AUA
symptom score.
PMID- 28411071
TI - Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell
Cancer with Tumor Thrombus.
AB - PURPOSE: Following surgery for nonmetastatic renal cell carcinoma with tumor
thrombus the risk of recurrence is significant but variable among patients. The
purpose of this study was to develop and validate a predictive nomogram for
individual estimation of recurrence risk following surgery for renal cell
carcinoma with venous tumor thrombus. MATERIALS AND METHODS: Comprehensive data
were collected on patients with nonmetastatic renal cell carcinoma and thrombus
treated at a total of 5 institutions from 2000 to 2013. Independent predictors of
recurrent renal cell carcinoma from a competing risks analysis were developed
into a nomogram. Predictive accuracy was compared between the development and
validation cohorts, and between the nomogram and the UISS (UCLA Integrated
Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models.
RESULTS: A total of 636 patients were analyzed, including the development cohort
of 465 and the validation cohort of 171. Independent predictors, including tumor
diameter, body mass index, preoperative hemoglobin less than the lower limit of
normal, thrombus level, perinephric fat invasion and nonclear cell histology,
were developed into a nomogram. Estimated 5-year recurrence-free survival was 49%
overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more
than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy
was similar in the development and validation cohorts (AUC 0.726 and 0.724,
respectively). Predictive accuracy of the thrombus nomogram was higher than that
of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04)
and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). CONCLUSIONS: We present a
predictive nomogram for postoperative recurrence in patients with nonmetastatic
renal cell carcinoma with venous thrombus. Improving individual postoperative
risk assessment may allow for better design and analysis of future adjuvant
clinical trials.
PMID- 28411072
TI - Outcomes of Patients with Renal Cell Carcinoma and Sarcomatoid Dedifferentiation
Treated with Nephrectomy and Systemic Therapies: Comparison between the Cytokine
and Targeted Therapy Eras.
AB - PURPOSE: We studied overall survival and prognostic factors in patients with
sarcomatoid renal cell carcinoma treated with nephrectomy and systemic therapy in
the cytokine and targeted therapy eras. MATERIALS AND METHODS: This is a
retrospective study of patients with sarcomatoid renal cell carcinoma who
underwent nephrectomy and received systemic therapy at our center in the cytokine
era (1987 to 2005) or the targeted therapy era (2006 to 2015). Multivariate
regression models were used to determine the association of covariables with
survival. RESULTS: Of the 199 patients with sarcomatoid renal cell carcinoma 167
(83.9%) died (median overall survival 16.5 months, 95% CI 15.2-20.9). Survival of
patients with clear cell histology was significantly longer vs those with
nonclear cell histology (p = 0.034). Patients with synchronous metastatic disease
had significantly shorter survival than patients with metachronous metastatic
disease (median 12.1 vs 23.3 months, p = 0.0064). Biopsy of the primary tumor or
a metastatic site could detect the presence of sarcomatoid features in only 7.5%
of cases. Although a significant improvement in survival rate was observed in the
first year in patients treated in the targeted therapy era (p = 0.011), this
effect was attenuated at year 2, disappeared at years 3 to 5 after diagnosis and
was not evident in patients with poor risk features. CONCLUSIONS: Patients with
sarcomatoid renal cell carcinoma still have poor prognosis with no clear long
term benefit of targeted therapy. This underscores the need to develop more
effective systemic therapies for these patients.
PMID- 28411073
TI - Arterial stiffness and elevated left ventricular filling pressure in patients at
risk for the development or a previous diagnosis of HF-A subgroup analysis from
the DIAST-CHF study.
AB - Left ventricular filling pressure (LVFP) is a marker for diastolic dysfunction
and heart failure (HF) with preserved ejection fraction (pEF). The interaction
between arterial stiffness (AS) and elevated LVFP has not been sufficiently
investigated. In 257 patients with preserved left ventricular ejection fraction
(mean age: 66 years, 53% female, mean left ventricular ejection fraction: 61%)
and at least one cardiovascular risk factor (eg, hypertension and diabetes) for
the development of HF or a previous diagnosis of HF, LVFP was estimated in
accordance with the recommendations of the American Society of Echocardiography
(elevated when E/e' >= 13, left atrial volume index >= 34 mL/m2). LVFP was
correlated with radial pulse wave analysis (augmentation index normalized by 75
b/min [AIx@75]) and carotid-femoral pulse wave velocity (cfPWV). Thirty-eight
percent of patients demonstrated an elevated LVFP. These patients were
significantly older (68.3 +/- 7.4 vs. 63.5 +/- 7.6 years, P < .001), demonstrated
a higher body mass index (29.8 +/- 4.6 vs. 28.0 +/- 5.0; P < .01), presented more
often with hypertension (89.7% vs. 73.1%, P < .01), hypercholesterolemia (32.0%
vs. 21.3%, P < .05), dyspnea on exertion (28.4% vs. 16.6%, P < .05), and
peripheral edema (25.3% vs. 10.2%, P < .01). cfPWV and AIx@75 and were
significantly elevated in patients with elevated LVFP (12.2 +/- 2.7 m/s vs. 10.5
+/- 2.6 m/s, P < .001, an 29.2 +/- 6.7% vs. 27.4 +/- 6.7%, P < .05 respectively).
cfPWV and AIx@75 were correlated with echocardiographic parameters, that is,
posterior wall thickness (r = 0.292, P < .001; r = 0.167, P < .01), left
ventricular mass index (r = 0.255, P < .001; r = -0.192, P < .01), e' (r =
0.508, P < .001; r = -0.159, P < .05), and E/e' (r = 0.380, P < .001; r = 0.200,
P < .01). cfPWV correlated with left atrial volume index (r = 0.189, P < .05) and
increasing E/A ratio (r = -0.334, P < .001). Multivariate linear regression
analysis demonstrated age and PWV as most important and independent predictors of
LVFP elevation in the cohort. Increased AS measured by cfPWV was associated with
an elevated LVFP in patients with preserved systolic function. Whether targeting
AS as a major component of diastolic dysfunction and HF with preserved ejection
fraction needs to be further investigated.
PMID- 28411074
TI - Low-dose sustained-release deoxycorticosterone acetate-induced hypertension in
Bama miniature pigs for renal sympathetic nerve denervation.
AB - Recently, the effectiveness of renal sympathetic nerve denervation for treatment
of hypertension has been doubted after SYMPLICITY HTN-3 trial. An ideal animal
model is still unavailable for preclinical study about catheter-based renal
sympathetic nerve denervation for treatment of hypertension. Traditional high
dose deoxycorticosterone acetate (DOCA)-induced hypertension pig model has some
problems due to extensive end-organ damage. Based on the similarity in the
anatomic characteristics of renal artery between pigs and humans, this study was
undertaken to establish a low-dose sustained-release DOCA-induced hypertension
model in pigs. A total of 14 pigs were subcutaneously implanted with low-dose
DOCA in the abdomen and cannulated from the femoral artery for the measurement of
blood pressure (BP). Plasma angiotensin I (Ang I), angiotensin II (Ang II),
plasma renin activity (PRA), aldosterone (Ald), creatinine, epinephrine, and
norepinephrine (NE) were determined before and after treatments. The kidneys were
collected and processed for hematoxylin and eosin staining, Masson-Goldner
trichromic, and periodic acid Schiff staining. Ten pigs survived for 1 month.
Mean BP significantly increased after 2-week treatment (P < .001). The plasma Ang
I, Ang II, PRA, and Ald significantly decreased (Ang I: 6.92 +/- 6.06 vs. 2.22 +/
3.08, P = .002; Ang II: 768.85 +/- 525.8 vs. 213.76 +/- 148.63, P = .003; PRA:
1.68 +/- 1.67 vs. 0.29 +/- 0.39, P = .008; Ald: 0.37 +/- 0.12 vs. 0.25 +/- 0.09,
P < .001), but norepinephrine significantly increased (7.59 +/- 4.57 vs. 16.96 +/
10.38, P = .021). Plasma creatinine remained unchanged. Hisotological
examination showed mild damage to the kidney. Low-dose sustained-release DOCA is
able to induce hypertension in pigs. A femoral catheter is not only helpful for
monitoring BP, but can be used to quickly exchange the renal sympathetic nerve
denervation equipment.
PMID- 28411075
TI - Effect of gender and adiposity on in vivo vascular function in young African
Americans.
AB - The relationship between obesity and high blood pressure is not as strong among
African Americans (AA) as compared to Caucasians. We designed the current study
to determine the effect of adiposity on vascular endothelial function (a
harbinger of hypertension) among young healthy AA without additional
cardiovascular disease risk factors. A total of 108 AA subjects (46 women)
between the ages of 18 and 45 years were recruited. All the subjects were
normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular
disease risk factor measurements (lipid, insulin resistance, and inflammatory
markers) were obtained. Vascular endothelial function was measured by brachial
artery flow-mediated dilation (FMD). Adiposity distribution was measured by using
magnetic resonance imaging scan. There were no gender differences in age and
levels of blood pressure, lipids, insulin resistance, and inflammatory markers.
Women had higher total body fat percentage and higher peripheral adiposity
compared to men. We observed that total and central adiposity did not correlate
significantly with brachial artery FMD in women (r = -0.12 and r = 0.23,
respectively; P = NS). However, in men, waist circumference was positively
associated with FMD (r = 0.3, P <= .05). Hyperemic flow was negatively correlated
significantly with total and central adiposity in men (r = -0.34 and r = -0.48,
respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P
= NS). Our study suggests that increased adiposity may pose greater risk to AA
men compared to AA women by adversely affecting resistance vessel function (as
measured by hyperemic flow). Larger studies are necessary to validate these
findings.
PMID- 28411076
TI - Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin
causes structural alterations accompanied by modulation at the epigenomic/genomic
level.
AB - BACKGROUND: NSAIDs are the most common class of painkillers and anti-inflammatory
agents. They also show other functions like chemoprevention and chemosuppression
for which they act at the protein but not at the genome level since they are
mostly anions at physiological pH, which prohibit their approach to the poly
anionic DNA. Complexing the drugs with bioactive metal obliterate their negative
charge and allow them to bind to the DNA, thereby, opening the possibility of
genome level interaction. To test this hypothesis, we present the interaction of
a traditional NSAID, Piroxicam and its copper complex with core histone and
chromatin. METHODS: Spectroscopy, DLS, and SEM studies were applied to see the
effect of the interaction on the structure of histone/chromatin. This was coupled
with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis
and qRT-PCR. RESULTS: The interaction of Piroxicam and its copper complex with
histone/chromatin results in structural alterations. Such structural alterations
can have different biological manifestations, but to test our hypothesis, we have
focused only on the accompanied modulations at the epigenomic/genomic level. The
complex, showed alteration of key epigenetic signatures implicated in
transcription in the global context, although Piroxicam caused no significant
changes. We have correlated such alterations caused by the complex with the
changes in global gene expression and validated the candidate gene expression
alterations. CONCLUSION AND GENERAL SIGNIFICANCE: Our results provide the proof
of concept that DNA binding ability of the copper complexes of a traditional
NSAID, opens up the possibility of modulations at the epigenomic/genomic level.
PMID- 28411077
TI - The "good-cop bad-cop" TGF-beta role in breast cancer modulated by non-coding
RNAs.
AB - BACKGROUND: Lack of early diagnosis methods and the development of drug
resistance are among the main reasons for increased mortality rates within breast
cancer patients. These two aspects are governed by specific pro-carcinogenic
modifications, where TGBbeta-induced EMT is one of the leading actors. Endowment
of the epithelial cells with mesenchymal characteristics allows them to migrate
and invade secondary tissues in order to form malignant sites and also confers
chemoresistance. TGFbeta which role switches from the tumor suppressor cytokine
to the oncogenic one favoring the tumor microenvironment regulates this process.
SCOPE OF REVIEW: This review aims to comprehensively present the updated TGFbeta
induced EMT in breast cancer, including the regulatory role of the non-coding
RNAs with focus on the miR-200 family and newly discovered lncRNAs such as
HOTAIRM1. Additionally, a new phenotype, P-EMT, also modulated by miR-200 and miR
34 families that form complex feedback loops with TGFbeta, SNAI1 and ZEB1/2 is
presented under an updated form. MAJOR CONCLUSIONS: The hallmarks of EMT are
becoming increasingly associated with aggressive forms of breast cancer and low
survival rates among patients. Considering that this phenotypical switch can
trigger drug resistance, invasion and metastasis, inhibition of EMT could
represent an important milestone in mammary cancer treatment. GENERAL
SIGNIFICANCE: The present review assembles the most recent data regarding TGFbeta
induced EMT, including the input of non-coding RNAs, contributing to the possible
development of new targeted treatment strategies for cancer patients.
PMID- 28411078
TI - Performance of the Xpert(r) Carba-R v2 in the daily workflow of a hygiene unit in
a country with a low prevalence of carbapenemase-producing Enterobacteriaceae.
AB - Early detection of patients colonised with carbapenemase-producing
Enterobacteriaceae (CPE) is crucial for implementing proper infection control
measures. Here we evaluated the biological performance of the Xpert(r) Carba-R v2
(Cepheid) in the daily workflow of a hygiene unit in a country with a low CPE
prevalence. Patients repatriated from countries known for high CPE prevalence or
contact patients of a known CPE carrier were targeted as being 'high-risk
patients' for CPE carriage. Between September 2015 and March 2016, 241 'high-risk
patients' for CPE carriage were screened using the Xpert(r) Carba-R v2 and by
plating on chromID(r) CARBA Smart medium (bioMerieux) with and without ertapenem
containing enrichment culture for 24 h. Of these patients, 81.7% were previously
hospitalised abroad and 18.3% were contact patients of known CPE carriers. The
Xpert(r) Carba-R v2 was able to detect 12 OXA-48-like, 1 KPC and 1 OXA-48
like/NDM carriers. For 2 of the 14 Xpert(r) Carba-R v2-positive samples, cultures
remained negative even on two additional screenings (performed at Days 4 and 7).
The Xpert(r) Carba-R v2 presents 100% sensitivity, 99.13% specificity, 85.71%
positive predictive value and 100% negative predictive value. This study
demonstrated that the Xpert(r) Carba-R v2 kit is well adapted for rapid screening
of high-risk patients even in low prevalence regions (in <1 h versus 24/48 h for
culture). This assay may guide infection control programmes to limit the spread
of CPE.
PMID- 28411079
TI - Commentary on "A meta-analysis but not a systematic review: an evaluation of the
Global BMI Mortality Collaboration".
PMID- 28411080
TI - A meta-analysis of individual participant data constructed to align with prior
expert views: comments on Bhupathiraju et al.
PMID- 28411081
TI - Identification of suitable reference genes for miRNA expression normalization in
gastric cancer.
PMID- 28411082
TI - A dominant negative FGFR1 mutation identified in a Kallmann syndrome patient.
AB - Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism
(IHH) with anosmia. Fibroblast growth factor receptor 1 (FGFR1) is one of KS
associated genes, accounts for approximately 10% of total patients. FGFR1
mutations have also been identified in more severe craniosynostosis syndromes,
and a subset of craniosynostosis syndromes-associated FGFR1 mutations show
dominant negative effect. In this study, we identified a novel FGFR1 mutation
(c.867G>A; p.W289X) in a KS patient. The p.W289X mutation leads premature
termination, producing a truncated FGFR1 without the transmembrane and
intracellular domains. Indeed, the W289X FGFR1 was secreted into culture medium.
Further, W289X FGFR1 interfered with the function of wild type receptor to induce
ERK1/2 phosphorylation. We therefore identified a dominant negative FGFR1
mutation in the KS patient, and this mutant FGFR1 may be used to decipher the
physiological function of FGFR1.
PMID- 28411083
TI - Overexpression of gma-miR1510a/b suppresses the expression of a NB-LRR domain
gene and reduces resistance to Phytophthora sojae.
AB - MicroRNAs (miRNAs) are universal regulators that repress target gene expression
in eukaryotes and play essential roles in plant immune responses. miRNAs were
recently found to be involved in soybean and Phytophthora sojae interactions.
Here, we screened miR1510, which was repressed in soybean during infection with
P. sojae, indicating that it might be involved in soybean response to pathogens.
To further uncover the roles of miRNAs in soybean, gma-miR1510a/b was
overexpressed in the hairy roots of soybean using an Arabidopsis miR319a
precursor as the backbone. The gma-miR1510a/b-overexpressing hairy roots showed
enhanced susceptibility to P. sojae, and the results showed that miR1510 guides
the cleavage of the Glyma.16G135500 gene, which encodes a classic type of plant
disease resistance-associated gene that harbors the Toll-interleukin-like
receptor (TIR) domain and nucleotide-binding site-leucine-rich repeat (NB-LRR)
domain. Noticeably, several biotic stresses and hormone-responsive cis-regulatory
elements were found to be present in the promoters of gma-MIR1510a and the target
gene. Collectively, the results obtained in the current study reveal that gma
miR1510 regulates the target NB-LRR immune receptor gene Glyma.16G135500 and thus
plays a crucial role in regulating the resistance of soybean to P. sojae.
PMID- 28411084
TI - Pelvic tuberculosis mimicking deep endometriosis.
AB - Pelvic tuberculosis is most frequently observed in developing countries and often
leads to the misdiagnosis of pelvic malignancy. We report the first case of
pelvic tuberculosis mimicking deep endometriosis.
PMID- 28411085
TI - Vaginal Myomectomy Using the Duhrssen (Longitudinal Median Cervical) Incision: A
Case Series of 19 Patients.
AB - STUDY OBJECTIVE: To examine demographics and outcome measures of women having
undergone vaginal excision of myomas through the Duhrssen (longitudinal median
cervical) incision. DESIGN: Prospective case series (Canadian Task Force
classification II-3). SETTING: A London teaching hospital. PATIENTS: Nineteen
patients with either a submucous myoma (type 1) located near the cervix or a
pedunculated intracavity myoma (type 0), excised via the Duhrssen incision.
INTERVENTIONS: Duhrssen (median longitudinal) incision on the anterior or
posterior cervical lip. MEASUREMENTS AND MAIN RESULTS: Duration of procedures,
intraoperative complications, estimated blood loss, length of stay, percent of
patients discharged in 24 hours, and readmission rates were studied. Between 2009
and 2016, 19 women had their myomas (submucous type 1, n = 17; pedunculated
intracavity type 0, n = 2) removed vaginally with the Duhrssen incision. The
median age at time of procedure was 46 years (range, 43-55), and the most common
indication was menorrhagia, which occurred in 90% of cases. The median myoma size
was 7 cm (range, 6-9), whereas the median duration of surgery was 60 minutes
(range, 40-120). Anterior cervical incisions were performed in 60% of cases, and
20% of the patients received gonadotropins for medical debulking of the myomas
before surgery. One patient sustained a bladder injury that occurred when making
the anterior cervical incision. The median length of stay was 8 hours (range, 6
36) and the median estimated blood loss was 90 mL (range, 50-150). The median
duration of follow-up was 4 years (range, .5-6), and no patients had symptoms
that were attributable to the procedure. CONCLUSION: This is a useful technique
that complements a minimally invasive surgeon's repertoire and is a viable
alternative when hysteroscopic myomectomy is deemed unsuitable because of
location and size of the myomas.
PMID- 28411086
TI - Early depletion of CA1 neurons and late neurodegeneration in a mouse tauopathy
model.
AB - Alzheimer's disease (AD) and tauopathies, such as frontotemporal dementia (FTD),
are characterized by formation of neurofibrillary tangles consisting of
hyperphosphorylated tau. Further neuropathological characteristics include
synaptic loss, neurodegeneration and brain atrophy. Here, we explored the
association between hyperphosphorylated tau species, brain atrophy, synaptic and
neuronal loss in a mouse model (rTg4510) carrying the human tau (hTau) P301L
mutation found in a familiar form of FTD. We established that hTau expression
during the first 6 postnatal weeks was important for the progression of tauopathy
in rTg4510 mice. Short term suppression of postnatal hTau expression delayed the
onset of tau pathology by approximately 6months in this model. Early postnatal
hTau expression was detrimental to CA1 neurons of the hippocampus and reduced
neuronal numbers in 6-10weeks young rTg4510 mice prior to the appearance of
hyperphosphorylated hTau species in the hippocampus. Hyperphosphorylated hTau
species emerged from 10 to 24weeks of age and were associated with increased
ubiquitin levels, gliosis, and brain atrophy and preceded the synaptic loss and
CA1 neurodegeneration that occurred at 48weeks of age. We present two
consequences of hTau expression in CA1 in rTg4510 mice: an early decrease in
neuron number already established prior to the presence of hyperphosphorylated
tau species and a later neurodegeneration dependent on hyperphosphorylated tau.
Neurodegeneration and synaptic protein loss were completely prevented when hTau
expression was suppressed prior to the appearance of hyperphosphorylated tau
species. Suppression of hTau expression after the onset of tau
hyperphosphorylation and tangle pathology initiated at 16weeks partially rescued
neuronal loss at 48weeks of age, while a reduction of neurodegeneration was no
longer possible when hTau suppression was introduced as late as at 24weeks of
age. Our results in rTg4510 mice argue that it is promising to lower
hyperphosphorylated tau species at early stages of tau pathology to protect from
neurodegeneration.
PMID- 28411087
TI - Pediatric extravasation injury management: A survey comparing 10 hospitals.
PMID- 28411088
TI - Hepatic Laceration due to Umbilical Venous Catheter Malpositioning.
PMID- 28411089
TI - Evidence for polymicrobial communities in explanted vascular filters and atheroma
debris.
AB - RATIONALE: Microbial communities have been implicated in a variety of disease
processes and have been intermittently observed in arterial disease; however, no
comprehensive unbiased community analysis has been performed. We hypothesize that
complex microbial communities may be involved in chronic vascular diseases as
well and may be effectively characterized by molecular assays. OBJECTIVE: The
main objective is to survey vascular debris, atheroma, and vascular filters for
polymicrobial communities consisting of prokaryotic and eukaryotic microbes,
specifically eukaryotic microbes. METHODS AND RESULTS: We examined vascular
aspirates of atheromatous debris or embolic protection filters in addition to
matched peripheral blood samples, from fifteen patients, as well as three
cadaveric coronary arteries from two separate patients, for microbial
communities. General fluorescence microscopy by Hoechst and ethidium bromide DNA
stains, prokaryotic and eukaryotic community analysis by Next Generation DNA
Sequencing (NGS), and a eukaryotic microbial 9 probe multiplexed quantitative PCR
were used to detect and characterize the presence of putative polymicrobial
communities. No prokaryotes were detected in peripheral blood; however, in 4 of 9
sequenced filters and in 2 of 7 sequenced atheroma debris samples, prokaryotic
populations were identified. By DNA sequencing, eukaryotic microbes were detected
in 4 of 15 blood samples, 5 of the 9 sequenced filters, and 3 of the 7 atheroma
debris samples. The quantitative multiplex PCR detected sequences consistent with
eukaryotic microbes in all 9 analyzed filter samples as well as 5 of the 7
atheroma debris samples. Microscopy reveals putative polymicrobial communities
within filters and atheroma debris. The main contributing prokaryotic species in
atheroma debris suggest a diverse and novel composition. Additionally,
Funneliformis mosseae, an arbuscular mycorrhizal fungus in the Glomeraceae
family, was detected in the coronary hard plaque from two patients. Well studied
biofilm forming bacteria were not detectable in circulating peripheral blood and
were not universally present in atheroma or filters. Analyses of the sequenced
eukaryotes are consistent with a diverse of array poorly studied environmental
eukaryotes. In summary, out of 15 patients, 6 exhibited molecular evidence of
prokaryotes and 14 had molecular evidence of eukaryotic and/or polymicrobial
communities in vivo, while 2 post-mortem coronary plaque samples displayed
evidence of fungi. CONCLUSION: Prokaryotes are not consistently observed in
atheroma debris or filter samples; however, detection of protozoa and fungi in
these samples suggests that they may play a role in arterial vascular disease or
atheroma formation.
PMID- 28411090
TI - Less frequent CD4 monitoring in virologically suppressed HIV.
PMID- 28411092
TI - Self-Assessed Kyphosis and Chewing Disorders Predict Disability and Mortality in
Community-Dwelling Older Adults.
AB - OBJECTIVE: It is clear that each trend of kyphosis with increased age and the
ability to eat firm foods with the back teeth (chewing ability) has a strong
influence on both the physical and mental condition of older people. Thus, this
study aimed to examine whether the combination of kyphosis and chewing disorders
was associated with mortality or the need for care under the new long-term care
insurance (LTCI) service requirement, over 3 years in community-dwelling older
Japanese adults. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We
analyzed the cohort data for older adults (65 years or older) from a prospective
study in Kami town. The response rate was 94.3%, and we followed 5094 older
individuals for 3 years. Thus, we analyzed 5083 older adults using multiple
imputation to manage missing data. OUTCOME: The outcomes were mortality or new
certifications for LTCI services in a 3-year period. MEASUREMENTS: We developed 3
groups by asking 2 self-reported questions on both "no kyphosis" and "good
chewing ability." The groups were no kyphosis and good chewing ability (GG),
kyphosis and poor chewing ability (BB), and kyphosis and good chewing ability or
no kyphosis and poor chewing ability (GB/BG). RESULTS: The prevalence of BB,
BG/GB, and GG were 8.9%, 40.3%, and 50.8%, respectively, in our survey. During
the 3-year follow-up period, 5.2% (n = 262) died and 13.9% (n = 708) individuals
were newly certified as needing LTCI services. As determined by multivariate
analyses, BG/GB older adults (adjusted hazard ratio: 1.3 [95% CI 1.1-1.6]) and BB
older adults (adjusted hazard ratio: 2.0 [95% CI 1.5-2.4]) had a significantly
higher risk of needing LTCI services than GG older adults. Similarly, BG/GB older
adults (adjusted hazard ratio: 1.5 [95% CI 1.1-2.0]) and BB older adults
(adjusted hazard ratio: 2.3 [95% CI 1.5-3.3]) had a significantly higher risk of
mortality than GG older adults did. CONCLUSION: The presence of kyphosis or poor
chewing ability was related to mortality and new certifications for LTCI
services, and we found an additive effect of these 2 factors related to frailty.
PMID- 28411093
TI - Association Between Diet Inflammatory Index and Osteoporotic Hip Fracture in
Elderly Chinese Population.
AB - BACKGROUND: Chronic inflammation provides the substrate for various mechanisms
involved in osteoporotic fracture. The Dietary Inflammatory Index (DII) could
shed light on the effect of the inflammatory potential of the diet on
osteoporotic hip fracture. OBJECTIVE: This study tested the hypothesis that
higher DII scores are associated with greater hip fracture risk in an elderly
Chinese population. METHODS: A 1:1 age- (+/-3 years), sex- and region-matched
case-control study of 1050 pairs (female/male: 781/269) of elderly (age range =
52-83 years) Chinese was conducted in Guangdong, China (2009-2015). Cases were
newly diagnosed (within 2 weeks) hip fracture patients and controls were
recruited from either communities (n = 835 controls) or the hospital (n = 215).
DII scores were calculated from self-reports using a validated 79-item food
frequency questionnaire. Odds ratios (ORs) and their 95% confidence intervals
(CIs) of the risk of hip fracture for DII scores were estimated from conditional
logistic regression. RESULTS: The multivariable-adjusted ORs (95% CIs) for hip
fracture across quartiles of DII scores were 1 (reference), 1.42 (1.01, 1.99),
1.63 (1.16, 2.28), and 2.44 (1.73, 3.45) (P trend <.001). Comparing extreme
quartiles, the adjusted ORs (95% CIs) for hip fractures were 2.08 (1.38, 3.12)
for female and 4.30 (1.89, 9.80) for male participants, respectively (P
interaction = .26). When stratified by the source of controls, a dose-response
positive relationship was observed between DII scores and hip fracture risk among
community-based controls but not those from the hospital (P interaction = .16).
CONCLUSIONS: A proinflammatory diet appears to be positively associated with hip
fracture risk.
PMID- 28411091
TI - Comparison of dynamic monitoring strategies based on CD4 cell counts in virally
suppressed, HIV-positive individuals on combination antiretroviral therapy in
high-income countries: a prospective, observational study.
AB - BACKGROUND: Clinical guidelines vary with respect to the optimal monitoring
frequency of HIV-positive individuals. We compared dynamic monitoring strategies
based on time-varying CD4 cell counts in virologically suppressed HIV-positive
individuals. METHODS: In this observational study, we used data from prospective
studies of HIV-positive individuals in Europe (France, Greece, the Netherlands,
Spain, Switzerland, and the UK) and North and South America (Brazil, Canada, and
the USA) in The HIV-CAUSAL Collaboration and The Centers for AIDS Research
Network of Integrated Clinical Systems. We compared three monitoring strategies
that differ in the threshold used to measure CD4 cell count and HIV RNA viral
load every 3-6 months (when below the threshold) or every 9-12 months (when above
the threshold). The strategies were defined by the threshold CD4 counts of 200
cells per MUL, 350 cells per MUL, and 500 cells per MUL. Using inverse
probability weighting to adjust for baseline and time-varying confounders, we
estimated hazard ratios (HRs) of death and of AIDS-defining illness or death,
risk ratios of virological failure, and mean differences in CD4 cell count.
FINDINGS: 47 635 individuals initiated an antiretroviral therapy regimen between
Jan 1, 2000, and Jan 9, 2015, and met the eligibility criteria for inclusion in
our study. During follow-up, CD4 cell count was measured on average every 4.0
months and viral load every 3.8 months. 464 individuals died (107 in threshold
200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1091 had AIDS
defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350,
and 459 in threshold 500). Compared with threshold 500, the mortality HR was 1.05
(95% CI 0.86-1.29) for threshold 200 and 1.02 (0.91.1.14) for threshold 350.
Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95-1.22)
for threshold 200 and 1.03 (0.96-1.12) for threshold 350. Compared with threshold
500, the 24 month risk ratios of virological failure (viral load more than 200
copies per mL) were 2.01 (1.17-3.43) for threshold 200 and 1.24 (0.89-1.73) for
threshold 350, and 24 month mean CD4 cell count differences were 0.4 (-25.5 to
26.3) cells per MUL for threshold 200 and -3.5 (-16.0 to 8.9) cells per MUL for
threshold 350. INTERPRETATION: Decreasing monitoring to annually when CD4 count
is higher than 200 cells per MUL compared with higher than 500 cells per MUL does
not worsen the short-term clinical and immunological outcomes of virally
suppressed HIV-positive individuals. However, more frequent virological
monitoring might be necessary to reduce the risk of virological failure. Further
follow-up studies are needed to establish the long-term safety of these
strategies. FUNDING: National Institutes of Health.
PMID- 28411094
TI - Association of Social Frailty With Both Cognitive and Physical Deficits Among
Older People.
AB - OBJECTIVES: Our objective was to investigate the association between social
frailty and cognitive and physical function among older adults. DESIGN: This was
a cross-sectional study. SETTING: We examined community-dwelling adults in Japan.
PARTICIPANTS: Participants comprised 4425 older Japanese people from the National
Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. MEASUREMENTS:
Social frailty was defined by using responses to 5 questions (going out less
frequently, rarely visiting friends, feeling unhelpful to friends or family,
living alone, and not talking with someone every day). Participants showing none
of these components were considered nonfrail; those showing 1 component were
considered prefrail; and those showing 2 or more components were considered
frail. To screen for cognitive deficits, we assessed memory, attention, executive
function, and processing speed. Having 2 or more tests with age-adjusted scores
of at least 1.5 standard deviations below the reference threshold was sufficient
to be characterized as cognitively deficient. To screen for physical function
deficits, we assessed walking speed (<1.0 m/s cut-off) and grip strength (<26 kg
for men; <18 kg for women cut-off). Scoring below the cut-off point on 1 or more
tests was sufficient to be characterized as physically deficient. RESULTS: The
prevalence of social frailty was the following: nonfrailty, 64.1% (N = 2835);
social prefrailty, 24.8% (N = 1097); social frailty, 11.1% (N = 493; P for trend
< .001). All cognitive function tests (word list memory, Trail Making Test parts
A and B, and the symbol digit-substitution task) significantly varied between
social frailty groups; physical function (gait speed and grip strength) also
varied between social frailty groups (all Ps for trend <.001). Referred to social
nonfrailty, social frailty was independently associated with each cognitive
deficit (odds ratio = 1.61, 95% confidence interval 1.13-2.30) and deficits in
physical function (odds ratio = 1.99, 95% confidence interval 1.57-2.52) after
adjusting for covariates. CONCLUSIONS: This study revealed that social frailty is
associated with both cognitive and physical function among Japanese older adults.
And social frailty status was also negatively associated with physical function.
Further studies are needed to elucidate if a casual association exists between
social frailty and cognitive and physical function.
PMID- 28411095
TI - Acute hepatitis E virus infection in a migrant population in North East Italy: A
retrospective analysis.
AB - OBJECTIVE: To study the epidemiological and clinical features of Hepatitis E
Virus (HEV) infection in a migrant population. METHODS: We performed a
retrospective chart review, identifying a cohort of 21 symptomatic patients of
migrant origin with confirmed HEV infection admitted in the period between
January 1995-November 2014. RESULTS: 20 (95%) patients came from South Asian
countries highly endemic for HEV, all positive for HEV genotype 1. Recent travel
to a highly endemic country was the most consistent risk factor identified in 90%
of cases, duration from return to Italy to hospitalization ranged from 10 to 120
days. Nausea and vomiting (100%), jaundice (95.2%), and anorexia (85.7%) were the
most common reported symptoms. Fever was present in 57.1% of cases. Transaminase
values were elevated in all patients and serum bilirubin was raised in 86% of
patients. We found no statistically significant differences between clinical
symptoms, laboratory results or duration of hospitalization in patients with co
morbidities compared to those without. We also report a secondary case of HEV
genotype 1 transmitted within Italy. CONCLUSION: Our study highlights the
epidemiological risk factors and clinical features of HEV infection in a migrant
population in Italy and should stimulate further research regarding the
prevalence and morbidity of HEV within migrant populations in Europe.
PMID- 28411096
TI - [Seroprevalence and vertical transmission of Chagas disease in a cohort of Latin
american pregnant women in a tertiary hospital in Madrid].
AB - BACKGROUND: Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is endemic in
Latin-America and is emerging in Spain due to immigration. The vertical
transmission rate is around 5%. A routine prenatal screening with serology of all
pregnant women from endemic areas is recommended to identify infected newborns,
allowing early treatment and cure. OBJECTIVE: The aim of this study was to
estimate the prevalence of positive Chagas serology in a cohort of pregnant women
from Latin-America and its vertical transmission. PATIENTS AND METHODS: An
observational, prospective, follow-up study was conducted on women with positive
serology to T. cruzi, as well as their newborns, from January 2013 to April 2015.
Congenital Chagas was ruled out using a PCR technique at birth and at 1 month,
and with serology at 9-12 months old. A child was considered infected when PCR
was positive, and uninfected when PCR was negative, and/or it had a negative
serology. RESULTS: Screening was performed on 1244 pregnant women from Latin
America, and there were positive results in 40 (prevalence 3.2%, 95% CI: 2.4
4.4%), with 85% of them from Bolivia. There was only one infected newborn (rate
of vertical transmission 2.8% (95% CI: 0-15%)), who had a positive PCR at birth.
Relative studies enabled an 8-year-old sister with an asymptomatic disease to be
diagnosed and treated. Both were treated successfully with benznidazole (later
the PCR and serology were negative). CONCLUSION: Screening during pregnancy in
Latin-American women helped to detect those with Chagas disease. The rate of
vertical transmission was 2.8%, in keeping with literature. Screening led to the
detection and treatment of previously unidentified familial cases.
PMID- 28411097
TI - [Acute liver failure related to inherited metabolic diseases in young children].
AB - INTRODUCTION: Pediatric acute liver failure (ALF) due to inherited metabolic
diseases (IMD) is a rare life-threatening condition with a poor prognosis. Early
intervention may be lifesaving. OBJECTIVE: To describe clinical presentation,
investigation and outcomes of ALF related to IMD in young children. MATERIAL AND
METHODS: Retrospective review of the medical records of children aged up to 24
months, admitted to a tertiary pediatric and neonatal Intensive Care Unit during
a 27-year period, fulfilling the ALF criteria, with documented metabolic
etiology. RESULTS: From 34 ALF cases, 18 were related to IMD: galactosemia (4),
mitochondrial DNA depletion syndrome (MDS) (3), ornithine transcarbamilase
deficiency (3), congenital defects of glycosylation (2), tyrosinemia type 1 (2),
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1), hereditary fructose
intolerance (1), classic methylmalonic aciduria (1) and citrulinemia type 1 (1).
The median age was 1.3 months. At least one previous suggestive sign/symptom of
IMD (vomiting, failure to thrive, hypotonia or developmental delay) was observed
in 67% of the cases. The most common physical signs at admission included:
hepatomegaly (72%), jaundice (67%) and encephalopathy (44%). The peak
laboratorial findings were: mean international normalizad ratio 4.5, median
lactate 5mmol/L, mean bilirubin 201MUmol/L, median alanine aminotransferase (ALT)
137 UI/L and median ammonia 177MUmol/L. One patient was submitted to liver
transplant in ALF context (MSD). The mortality rate was 44%. DISCUSSION: The
identification of IMD as a frequent cause of ALF allowed specific therapeutic
measures and adequate family counselling. Particular clinical features and
moderated ALT and bilirubin levels can lead to its suspicion.
PMID- 28411098
TI - The Impact of Postoperative Conformal Radiotherapy after Radical Surgery on
Survival and Recurrence in Pathologic T3N0M0 Esophageal Carcinoma: A Propensity
Score-Matched Analysis.
AB - INTRODUCTION: The role of conformal radiotherapy (cRT) in thoracic esophageal
squamous cell carcinoma (TESCC) has not been addressed in adjuvant settings. The
aim of this study was to investigate whether postoperative radiotherapy using cRT
after an R0 resection improves outcomes in pT3N0M0 TESCC compared with resection
alone. METHODS: This study included 678 patients with pT3N0M0 TESCC who were
treated at the Cancer Hospital, Chinese Academy of Medical Sciences, from January
2004 to December 2011. The patients were divided into two groups: a surgery plus
cRT group (S+cRT group) comprising patients who underwent cRT after an R0
resection and a surgery group (S group), comprising a control group of patients
who underwent an R0 resection alone. Propensity score matching was used to create
patient groups that were balanced across several covariates (n = 83 in each
group). Outcome measures included overall survival (OS), disease-free survival
(DFS), and recurrence. RESULTS: In the overall study cohort, 5-year OS (75.2%
versus 58.5%, p = 0.004) and DFS (71.8% versus 49.2%, p = 0.001) rates were
significantly higher in the S+cRT group than in the S group. These data were
confirmed in the matched samples (5-year OS, 75.7% versus 58.8% [p = 0.017]; DFS,
71.7% versus 50.3% [p = 0.009]). The overall (p = 0.001) and locoregional (p =
0.004) recurrence rates in the S+cRT group were significantly lower than in the S
group. Multivariate Cox analyses in the matched samples revealed that surgery and
postoperative cRT were independently associated with longer OS (hazard ratio =
0.505, 95% confidence interval: 0.291-0.876, p = 0.015) and longer DFS (hazard
ratio = 0.513, 95% confidence interval: 0.309-0.854, p = 0.010) than resection
alone. CONCLUSIONS: Postoperative radiotherapy using cRT is strongly associated
with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter,
randomized phase III clinical trial is warranted to confirm these findings.
PMID- 28411099
TI - Robot-assisted Transplanted Ureteral Stricture Management.
AB - OBJECTIVE: To assess the feasibility of robot-assisted transplanted ureteral
reimplantation as a minimally invasive alternative to open surgery. MATERIAL AND
METHODS: Between August 2015 and March 2016, 5 patients presented with
transplanted ureteral strictures after failure of a previous endoscopic
management. All patients underwent robot-assisted ureteral reimplantation.
Patients' demographics, perioperative outcomes, and complications are reported.
RESULTS: All patients presented with deterioration of kidney function with or
without recurrent urinary tract infection. Two patients had short strictures (<1
cm) and 2 had long strictures (>1 cm), whereas 1 patient had a nitinol ureteral
stent in situ. The location of the stricture varied among these patients with 3
distal and 1 proximal. Intraoperatively, 3 patients had a modified Lich-Gregoir
reimplantation and 2 patients had a pyelovesicostomy. The mean operative time was
164 (+/-52) minutes. There were no intraoperative complications, conversion to
open surgery, or significant blood loss necessitating blood transfusion. There
were no urine leaks in the immediate or late postoperative period. One patient
developed a Clavien grade IVa complication (sepsis). The median length of stay,
the duration of catheterization, and the duration of stenting were 1 day (range 1
5 days), 7 days (range 6-14 days), and 39 days (range 25-51 days), respectively.
After a median follow-up of 79 days (range 40-139 days), no strictures or delayed
leakages were identified. CONCLUSION: Robot-assisted transplanted ureteral
reimplantation is technically feasible. With a larger number of cases and a
longer follow-up, robot-assisted transplanted ureteral reimplantation may provide
a new and effective, minimally invasive alternative for the treatment of this
complex surgical problem.
PMID- 28411100
TI - W-pouch With Modified Non-isolated Extra Limb for Continence in Cutaneous
Diversion After Radical Cystectomy.
AB - OBJECTIVE: To report the functional results of continent cutaneous ileal urinary
diversion using modified W-pouch with non-isolated extra limb for continence.
PATIENTS AND METHODS: From January 2013 to January 2016, 21 patients with muscle
invasive bladder cancer with median (interquartile range) of 59 (56.5-62.5) years
old underwent radical cystectomy with pelvic lymphadenectomy; they then had an
ileal continent cutaneous pouch constructed from W-pouch with non-isolated extra
limb for continence. The technique entails the creation of a detubularized ileal
W-pouch with extra limb fashioned from 59 cm of the terminal ileum. This extra
limb is not isolated from the pouch. The proximal part of this limb is tailored
and fixed in a subserous extramural tunnel for continence, whereas the distal
part is left continuous with the pouch. The median (interquartile range) of
follow up was 12 (8-17) months. Evaluation of the technique included operative
time, continence efficiency, overall complications, and quality of life
questionnaire for the patients. RESULTS: The median (interquartile range) of
operative time of the operation was 4.7 (3.9-5.4) hours. The median
(interquartile range) of operative time of the cutaneous pouch creation was 39
(33-43) minutes. No perioperative mortality had occurred. The incidence of
continence was 95.2%. The overall complications were 42.8%, and most of them were
grade 1 or 2 on Clavien-Dindo classification system. CONCLUSION: Modification of
W-pouch with non-isolated extra limb as continent cutaneous pouch can simplify
the technique and shorten the operative time with efficient continence, less side
effects, and good quality of life.
PMID- 28411101
TI - Surgical Management of Primary Spindle Cell Sarcoma of Prostate.
AB - Primary spindle cell sarcoma of prostate is an extremely rare malignancy and very
few cases of it have been reported Ozturk and Sivrikoz, 2013; Hansel and Epstein,
2006. We searched the literature through MEDLINE database using PubMed and Scopus
for the articles published between January 1988 and September 2016. Our search
was limited to the following keywords: "spindle cell sarcoma," "prostate," and
"surgical management." Most of the papers focused on histopathology of the tumor,
and very few discussed surgical management. We present a case of localized
primary spindle cell sarcoma of the prostate operated at our institute with the
difficulties we faced and their management.
PMID- 28411102
TI - ZL006 protects spinal cord neurons against ischemia-induced oxidative stress
through AMPK-PGC-1alpha-Sirt3 pathway.
AB - Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades,
including activation of glutamate receptors and downstream signaling. Post
synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS)
with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in
the CNS. This molecular complex-mediated cytotoxicity has been implicated in
brain ischemia, but its role in SCI has not been determined. The goal of the
study was to investigate the potential protective effects of ZL006, a small
molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model
induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons.
We found that ZL006 reduced OGD-induced lactate dehydrogenase (LDH) release,
neuronal apoptosis and loss of cell viability. This protection was accompanied by
the preservation of mitochondrial function, as evidenced by reduced mitochondrial
oxidative stress, attenuated mitochondrial membrane potential (MMP) loss, and
enhanced ATP generation. In addition, ZL006 stimulated mitochondrial enzyme
activities and SOD2 deacetylation in a Sirt3-dependent manner. The results of
western blot analysis showed that ZL006 increased the activation of AMPK-PGC
1alpha-Sirt3 pathway, and the beneficial effects of ZL006 was partially abolished
by AMPK inhibitor and PGC-1alpha knockdown. Therefore, our present data showed
that, by the AMPK-PGC-1alpha-Sirt3 pathway, ZL006 protects spinal cord neurons
against ischemia through reducing mitochondrial oxidative stress to prevent
apoptosis.
PMID- 28411103
TI - Endogenous regeneration: Engineering growth factors for stroke.
AB - Despite the efforts in developing therapeutics for stroke, recombinant tissue
plasminogen activator (rtPA) remains the only FDA approved drug for ischemic
stroke. Regenerative medicine targeting endogenous growth factors has drawn much
interest in the clinical field as it provides potential restoration for the
damaged brain tissue without being limited by a narrow therapeutic window. To
date, most of the translational studies using regenerative medicines have
encountered problems and failures. In this review, we discuss the effects of some
trophic factors which include of erythropoietin (EPO), brain derived neurotrophic
factor (BDNF), granulocyte-colony stimulating factor (G-CSF), vascular
endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal
growth factor (EGF) and heparin binding epidermal growth factor (HB-EGF) in
experimental ischemic stroke models and elaborate the lost in translation of the
candidate growth factors from bench to bedside. Several new methodologies have
been developed to overcome the caveats in translational studies. This review
highlights the latest bioengineering approaches including the controlled release
and delivery of growth factors by hydrogel-based scaffolds and the enhancement of
half-life and selectivity of growth factors by a novel approach facilitated by
glycosaminoglycans.
PMID- 28411104
TI - Genetic control of oromotor phenotypes: A survey of licking and ingestive
behaviors in highly diverse strains of mice.
AB - In order to examine genetic influences on fluid ingestion, 20-min intake of
either water or 0.1M sucrose was measured in a lickometer in 18 isogenic strains
of mice, including 15 inbred strains and 3 F1 hybrid crosses. Intake and licking
data were examined at a number of levels, including lick rate as defined by mean
or median interlick interval, as well as several microstructural parameters (i.e.
burst-pause structure). In general, strain variation for ingestive phenotypes
were correlated across water and sucrose in all strains, indicating fundamental,
rather than stimulus-specific, mechanisms of intake. Strain variation was
substantial and robust, with heritabilities for phenotypes ranging from 0.22 to
0.73. For mean interlick interval (MPI; a measure of lick rate) strains varied
continuously from 94.3 to 127.0ms, a range consistent with previous studies.
Furthermore, variation among strains for microstructural traits such as burst
size and number suggested that strains possess different overall ingestive
strategies, with some favoring more short bursts, and others favoring fewer, long
bursts. Strains also varied in cumulative intake functions, exhibiting both
linear and decelerated rates of intake across the session.
PMID- 28411105
TI - Long-Term Cognitive Functioning and Psychological Well-Being in Surgically
Treated Patients with Low-Grade Glioma.
AB - OBJECTIVE: The aim of this work is to provide an in-depth investigation of the
impact of low-grade gliomas (LGG) and their surgery on patients' cognitive and
emotional functioning and well-being, carried out via a comprehensive and
multiple-measure psychological and neuropsychological assessment. PATIENTS AND
METHODS: Fifty surgically treated patients with LGG were evaluated 40 months
after surgery on their functioning over 6 different cognitive domains, 3 core
affective/emotional aspects, and 3 different psychological well-being measures to
obtain a clearer picture of the long-term impact of illness and surgery on their
psychological and relational world. Close relatives were also involved to obtain
an independent measure of the psychological dimensions investigated. RESULTS:
Cognitive status was satisfactory, with only mild short-term memory difficulties.
The affective and well-being profile was characterized by mild signs of
depression, good satisfaction with life and psychological well-being, and good
personality development, with patients perceiving themselves as stronger and
better persons after illness. However, patients showed higher emotional
reactivity, and psychological well-being measures were negatively affected by
epileptic burden. Well-being was related to positive affective/emotional
functioning and unrelated to cognitive functioning. Good agreement between
patients and relatives was found. CONCLUSIONS: In the long-term, patients
operated on for LGG showed good cognitive functioning, with no significant long
term cognitive sequelae for the extensive surgical approach. Psychologically,
patients appear to experience a deep psychological change and maturation, closely
resembling that of so-called posttraumatic growth, which, to our knowledge, is
for the first time described and quantified in patients with LGG.
PMID- 28411106
TI - Mass spectrometry imaging shows major derangements in neurogranin and in purine
metabolism in the triple-knockout 3*Tg Alzheimer mouse model.
AB - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging
(MSI) can simultaneously measure hundreds of biomolecules directly from tissue.
Using different sample preparation strategies, proteins and metabolites have been
profiled to study the molecular changes in a 3*Tg mouse model of Alzheimer's
disease. In comparison with wild-type (WT) control mice MALDI-MSI revealed
Alzheimer's disease-specific protein profiles, highlighting dramatic reductions
of a protein with m/z 7560, which was assigned to neurogranin and validated by
immunohistochemistry. The analysis also revealed substantial metabolite changes,
especially in metabolites related to the purine metabolic pathway, with a shift
towards an increase in hypoxanthine/xanthine/uric acid in the 3*Tg AD mice
accompanied by a decrease in AMP and adenine. Interestingly these changes were
also associated with a decrease in ascorbic acid, consistent with oxidative
stress. Furthermore, the metabolite N-arachidonyl taurine was increased in the
diseased mouse brain sections, being highly abundant in the hippocampus. Overall,
we describe an interesting shift towards pro-inflammatory molecules (uric acid)
in the purinergic pathway associated with a decrease in anti-oxidant level
(ascorbic acid). Together, these observations fit well with the increased
oxidative stress and neuroinflammation commonly observed in AD. This article is
part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and
Prof. Peter Hoffmann.
PMID- 28411107
TI - Pulmonary hypertension due to left heart disease.
AB - Pulmonary hypertension due to left heart disease, also known as group 2 pulmonary
hypertension according to the European Society of Cardiology/European Respiratory
Society classification, is the most common cause of pulmonary hypertension. In
patients with left heart disease, the development of pulmonary hypertension
favours right heart dysfunction, which has a major impact on disease severity and
outcome. Over the past few years, this condition has been considered more
frequently. However, epidemiological studies of group 2 pulmonary hypertension
are less exhaustive than studies of other causes of pulmonary hypertension. In
group 2 patients, pulmonary hypertension may be caused by an isolated increase in
left-sided filling pressures or by a combination of this condition with increased
pulmonary vascular resistance, with an abnormally high pressure gradient between
arteries and pulmonary veins. A better understanding of the conditions underlying
pulmonary hypertension is of key importance to establish a comprehensive
diagnosis, leading to an adapted treatment to reduce heart failure morbidity and
mortality. In this review, epidemiology, mechanisms and diagnostic approaches are
reviewed; then, treatment options and future approaches are considered.
PMID- 28411108
TI - Causes and temporal trends in procedural deaths after transcatheter aortic valve
implantation.
AB - BACKGROUND: The causes of procedural deaths after transcatheter aortic valve
implantation (TAVI) have been scarcely detailed. AIMS: To assess these causes and
their temporal trends since the beginning of the TAVI era. METHODS: From October
2006 to April 2014, 601 consecutive high-risk/inoperable patients with severe
aortic stenosis underwent TAVI using the Edwards SAPIEN or SAPIEN XT or the
Medtronic CoreValve. The transfemoral route was the default approach; the
transapical or left subclavian approaches were alternative options. Patients were
divided into three tertiles according to the date of the procedure. RESULTS:
Procedural death occurred in 45 patients (7.5%), with a median+/-standard
deviation age of 83+/-7 years; 23 were men (51%) and the mean logistic EuroSCORE
was 26+/-16%. The main cause of death was heart failure (n=19, 42%), followed by
cardiac rupture (n=12, 27%), intensive care complications (n=9, 20%) and vascular
complications (n=5, 11%). The mortality rate was higher after transapical than
transfemoral TAVI (17% vs. 5%; P<0.001). The mortality rate decreased over time
(11.9% in the first tertile, 6.0% in the second and 4.5% in the third [P=0.007]),
driven by a reduction in heart failure-related deaths (6.5% in the first tertile
vs. 1.5% in the third; P=0.011). Vascular complication-related deaths disappeared
in the third tertile. However, there was no decrease in deaths related to cardiac
ruptures and intensive care complications. CONCLUSIONS: The procedural mortality
rate of TAVI decreased over time, driven by the decrease in heart failure-related
deaths. However, efforts should continue to prevent cardiac ruptures and improve
the outcomes of patients requiring intensive care after TAVI.
PMID- 28411109
TI - Letter to the Editor concerning "Hajdu Cheney syndrome; report of a novel NOTCH2
mutation and treatment with denosumab" by G. Adami et al. Bone 2016;92:150-156.
PMID- 28411110
TI - Impaired WNT signaling and the spine-Heterozygous WNT1 mutation causes severe age
related spinal pathology.
AB - BACKGROUND: WNT signaling plays a major role in bone and cartilage metabolism.
Impaired WNT/beta-catenin signaling leads to early-onset osteoporosis, but
specific features in bone and other tissues remain inadequately characterized. We
have identified two large Finnish families with early-onset osteoporosis due to a
heterozygous WNT1 mutation c.652T>G, p.C218G. This study evaluated the impact of
impaired WNT/beta-catenin signaling on spinal structures. METHODS: Altogether 18
WNT1 mutation-positive (age range 11-76years, median 49years) and 14 mutation
negative subjects (10-77years, median 43years) underwent magnetic resonance
imaging (MRI) of the spine. The images were reviewed for spinal alignment,
vertebral compression fractures, intervertebral disc changes and possible
endplate deterioration. The findings were correlated with clinical data. RESULTS:
Vertebral compression fractures were present in 78% (7/9) of those aged over
50years but were not seen in younger mutation-positive subjects. All those with
fractures had several severely compressed vertebrae. Altogether spinal
compression fractures were present in 39% of those with a WNT1 mutation. Only 14%
(2/14) mutation-negative subjects had one mild compressed vertebra each. The
mutation-positive subjects had a higher mean spinal deformity index (4.0+/-7.3 vs
0.0+/-0.4) and more often increased thoracic kyphosis (Z-score>+2.0 in 33% vs
0%). Further, they had more often Schmorl nodes (61% vs 36%), already in
adolescence, and their intervertebral discs were enlarged. CONCLUSION:
Compromised WNT signaling introduces severe and progressive changes to the spinal
structures. Schmorl nodes are prevalent even at an early age and increased
thoracic kyphosis and compression fractures become evident after the age of
50years. Therapies targeting the WNT pathway may be an effective way to prevent
spinal pathology not only in those harboring a mutation but also in the general
population with similar pathology.
PMID- 28411111
TI - S-SulfPred: A sensitive predictor to capture S-sulfenylation sites based on a
resampling one-sided selection undersampling-synthetic minority oversampling
technique.
AB - Protein S-sulfenylation is a reversible post-translational modification involving
covalent attachment of hydroxide to the thiol group of cysteine residues, which
is involved in various biological processes including cell signaling, response to
stress and protein functions. Herein we present S-SulfPred, a support vector
machine based model to capture potential S-sulfenylation sites and improve the
efficiency and relevance of experimental identification of protein S
sulfenylation sites. One-sided selection (OSS) undersampling and synthetic
minority oversampling technique (SMOTE) oversampling were combined to establish
balanced training datasets. This approach is shown to perform better than using
only OSS or SMOTE in an independent test. The best combination of position
specific amino acid propensity and five physicochemical properties of amino acids
were selected to optimize the predictor performance. Using S-SulfPred, we achieve
an average sensitivity of 74.62%, and an average specificity of 71.62% on
independent datasets. Compared with other published tools, S-SulfPred attains
both higher sensitivity and specificity. We not only propose a highly accurate
method to predict protein S-sulfenylation sites, but also provide insights that
could improve the efficiency of other bioinformatics tools.
PMID- 28411112
TI - Morphine Use in the ED and Outcomes of Patients With Acute Heart Failure: A
Propensity Score-Matching Analysis Based on the EAHFE Registry.
AB - OBJECTIVE: The objective was to determine the relationship between short-term
mortality and intravenous morphine use in ED patients who received a diagnosis of
acute heart failure (AHF). METHODS: Consecutive patients with AHF presenting to
34 Spanish EDs from 2011 to 2014 were eligible for inclusion. The subjects were
divided into those with (M) or without IV morphine treatment (WOM) groups during
ED stay. The primary outcome was 30-day all-cause mortality, and secondary
outcomes were mortality at different intermediate time points, in-hospital
mortality, and length of hospital stay. We generated a propensity score to match
the M and WOM groups that were 1:1 according to 46 different epidemiological,
baseline, clinical, and therapeutic factors. We investigated independent risk
factors for 30-day mortality in patients receiving morphine. RESULTS: We included
6,516 patients (mean age, 81 [SD, 10] years; 56% women): 416 (6.4%) in the M and
6,100 (93.6%) in the WOM group. Overall, 635 (9.7%; M, 26.7%; WOM, 8.6%) died by
day 30. After propensity score matching, 275 paired patients constituted each
group. Patients receiving morphine had a higher 30-day mortality (55 [20.0%] vs
35 [12.7%] deaths; hazard ratio, 1.66; 95% CI, 1.09-2.54; P = .017). In patients
receiving morphine, death was directly related to glycemia (P = .013) and
inversely related to the baseline Barthel index and systolic BP (P = .021) at ED
arrival (P = .021). Mortality was increased at every intermediate time point,
although the greatest risk was at the shortest time (at 3 days: 22 [8.0%] vs 7
[2.5%] deaths; OR, 3.33; 95% CI, 1.40-7.93; P = .014). In-hospital mortality did
not increase (39 [14.2%] vs 26 [9.1%] deaths; OR, 1.65; 95% CI, 0.97-2.82; P =
.083) and LOS did not differ between groups (median [interquartile range] in M, 8
[7]; WOM, 8 [6]; P = .79). CONCLUSIONS: This propensity score-matched analysis
suggests that the use of IV morphine in AHF could be associated with increased 30
day mortality.
PMID- 28411114
TI - Circulating Biologically Active Adrenomedullin (bio-ADM) Predicts Hemodynamic
Support Requirement and Mortality During Sepsis.
AB - BACKGROUND: The biological role of adrenomedullin (ADM), a hormone involved in
hemodynamic homeostasis, is controversial in sepsis because administration of
either the peptide or an antibody against it may be beneficial. METHODS: Plasma
biologically active ADM (bio-ADM) was assessed on days 1, 2, and 7 after
randomization of 956 patients with sepsis or septic shock to albumin or
crystalloids for fluid resuscitation in the multicenter Albumin Italian Outcome
Sepsis trial. We tested the association of bio-ADM and its time-dependent
variation with fluid therapy, vasopressor administration, organ failures, and
mortality. RESULTS: Plasma bio-ADM on day 1 (median [Q1-Q3], 110 [59-198] pg/mL)
was higher in patients with septic shock, associated with 90-day mortality,
multiple organ failures and the average extent of hemodynamic support therapy
(fluids and vasopressors), and serum lactate time course over the first week.
Moreover, it predicted incident cardiovascular dysfunction in patients without
shock at enrollment (OR [95% CI], 1.9 [1.4-2.5]; P < .0001, for an increase of 1
interquartile range of bio-ADM concentration). bio-ADM trajectory during the
first week of treatment clearly predicted 90-day mortality after adjustment for
clinically relevant covariates (hazard ratio [95% CI], 1.3 [1.2-1.4]; P < .0001),
and its reduction below 110 pg/mL at day 7 was associated with a marked reduction
in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were
not dependent on albumin treatment. CONCLUSIONS: In patients with sepsis, the
circulating, biologically active form of ADM may help individualizing hemodynamic
support therapy, while avoiding harmful effects. Its possible pathophysiologic
role makes bio-ADM a potential candidate for future targeted therapies. TRIAL
REGISTRY: ClinicalTrials.gov; No.: NCT00707122.
PMID- 28411113
TI - Restrictive Spirometry Pattern Is Associated With Increased Arterial Stiffness in
Men and Women.
AB - BACKGROUND: There is growing evidence that pulmonary function impairment is
related to cardiovascular events and death. Some studies have shown that the
level of FVC is negatively related to arterial stiffness, but most studies were
confined to men, and none of them examined the association of the presence of
restrictive spirometry pattern with arterial stiffness. Therefore, this study
aimed to investigate the association of restrictive spirometry pattern with
arterial stiffness by sex. METHODS: This study recruited 2,961 subjects after
excluding those with (1) obstructive lung disease, as defined by history and
pulmonary function test; (2) history of asthma, lung cancer, tuberculosis,
coronary heart disease, stroke, or any pulmonary structural deformities; and (3)
medications influencing BP, plasma glucose, lipid profile, and pulmonary function
test. Restrictive spirometry pattern was diagnosed as an FVC < 80% of the
predicted value and an FEV1/FVC ratio >= 70%. Increased arterial stiffness was
defined as right brachial ankle pulse wave velocity (baPWV) >= 1,400 cm/s.
RESULTS: In both men and women, FVC was negatively associated with the baPWV
level. Restrictive spirometry pattern was positively associated with increased
arterial stiffness in both men and women (men: OR, 2.16; 95% CI, 1.33-3.50;
women: OR, 1.95; 95% CI, 1.02-3.72) after adjustment for other clinical
variables. CONCLUSIONS: Both restrictive spirometry pattern and reduced FVC were
associated with a higher risk of arterial stiffness, not only in men but also in
women. Clinically, assessment of arterial stiffness might be considered in
individuals with restrictive spirometry pattern.
PMID- 28411115
TI - Sponging off nature for new drug leads.
AB - Marine sponges have consistently been the richest source of new marine natural
products with unprecedented chemical scaffolds and potent biological activities
that have been reported in the chemical literature since the early 1970s. During
the last 40years, chemists in the Andersen laboratory at UBC, in collaboration
with biologists, have discovered many novel bioactive sponge natural products.
Four experimental drug candidates for treatment of inflammation and cancer, that
were inspired by members of this sponge natural product collection, have
progressed to phase I/II/III clinical trials. This review recounts the scientific
stories behind the discovery and development of these four drug candidates;
IPL576,092, HTI-286 (Taltobulin), EPI-506 (Ralaniten acetate), and AQX-1125.
PMID- 28411116
TI - Global field synchronization in gamma range of the sleep EEG tracks sleep depth:
Artifact introduced by a rectangular analysis window.
AB - BACKGROUND: Investigating functional connectivity between brain networks has
become an area of interest in neuroscience. Several methods for investigating
connectivity have recently been developed, however, these techniques need to be
applied with care. We demonstrate that global field synchronization (GFS), a
global measure of phase alignment in the EEG as a function of frequency, must be
applied considering signal processing principles in order to yield valid results.
NEW METHOD: Multichannel EEG (27 derivations) was analyzed for GFS based on the
complex spectrum derived by the fast Fourier transform (FFT). We examined the
effect of window functions on GFS, in particular of non-rectangular windows.
RESULTS: Applying a rectangular window when calculating the FFT revealed high GFS
values for high frequencies (>15Hz) that were highly correlated (r=0.9) with
spectral power in the lower frequency range (0.75-4.5Hz) and tracked the depth of
sleep. This turned out to be spurious synchronization. With a non-rectangular
window (Tukey or Hanning window) these high frequency synchronization vanished.
Both, GFS and power density spectra significantly differed for rectangular and
non-rectangular windows. COMPARISON WITH EXISTING METHOD(S): Previous papers
using GFS typically did not specify the applied window and may have used a
rectangular window function. However, the demonstrated impact of the window
function raises the question of the validity of some previous findings at higher
frequencies. CONCLUSIONS: We demonstrated that it is crucial to apply an
appropriate window function for determining synchronization measures based on a
spectral approach to avoid spurious synchronization in the beta/gamma range.
PMID- 28411117
TI - In vitro alpha-synuclein neurotoxicity and spreading among neurons and astrocytes
using Lewy body extracts from Parkinson disease brains.
AB - Synucleinopathies are a group of diseases characterized by the presence of
intracellular protein aggregates containing alpha-synuclein (alpha-syn). While
alpha-syn aggregates have been shown to induce multimodal cellular dysfunctions,
uptake and transport mechanisms remain unclear. Using high-content imaging on
cortical neurons and astrocytes, we here define the kinetics of neuronal and
astrocytic abnormalities induced by human-derived alpha-syn aggregates grounding
the use of such system to identify and test putative therapeutic compounds. We
then aimed at characterizing uptake and transport mechanisms using primary
cultures of cortical neurons and astrocytes either in single well or in
microfluidic chambers allowing connection between cells and cell-types. We report
that astrocytes take up alpha-syn-aggregates far more efficiently than neurons
through an endocytic event. We also highlight that active alpha-syn transport
occurs between cells and any cell-types. Of special interest regarding the
disease, we also show that uptake and spreading of alpha-syn from astrocytes to
neurons can lead to neuronal death. Altogether, we here show that patients
derived alpha-synuclein aggregates, which are taken up by neurons and astrocytes,
induce a differential endogenous response in the two cell types including a
peculiar astrocytic toxic gain-of-function that leads to neuronal death.
PMID- 28411118
TI - Regulation of motor proteins, axonal transport deficits and adult-onset
neurodegenerative diseases.
AB - Neurons affected in a wide variety of unrelated adult-onset neurodegenerative
diseases (AONDs) typically exhibit a "dying back" pattern of degeneration, which
is characterized by early deficits in synaptic function and neuritic pathology
long before neuronal cell death. Consistent with this observation, multiple
unrelated AONDs including Alzheimer's disease, Parkinson's disease, Huntington's
disease, and several motor neuron diseases feature early alterations in kinase
based signaling pathways associated with deficits in axonal transport (AT), a
complex cellular process involving multiple intracellular trafficking events
powered by microtubule-based motor proteins. These pathogenic events have
important therapeutic implications, suggesting that a focus on preservation of
neuronal connections may be more effective to treat AONDs than addressing
neuronal cell death. While the molecular mechanisms underlying AT abnormalities
in AONDs are still being analyzed, evidence has accumulated linking those to a
well-established pathological hallmark of multiple AONDs: altered patterns of
neuronal protein phosphorylation. Here, we present a short overview on the
biochemical heterogeneity of major motor proteins for AT, their regulation by
protein kinases, and evidence revealing cell type-specific AT specializations.
When considered together, these findings may help explain how independent
pathogenic pathways can affect AT differentially in the context of each AOND.
PMID- 28411120
TI - Effectiveness and safety of rivaroxaban and warfarin in patients with unprovoked
venous thromboembolism: a propensity-matched nationwide cohort study.
AB - BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism are collectively
known as venous thromboembolism (VTE), which is a common vascular disease and a
major cause of morbidity and mortality worldwide. We compare effectiveness and
safety of rivaroxaban versus warfarin in a prospective cohort of routine care
patients with incident unprovoked VTE. METHODS: In this propensity-matched cohort
study, we linked nationwide Danish health registries to identify all patients
with a first hospital diagnosis of unprovoked VTE who were new users of
rivaroxaban or warfarin. Excluded patients included those who had not been
residents in Denmark for at least 1 year before VTE diagnosis, patients with
outpatient VTE diagnosis only, patients with other indications for oral
anticoagulation treatment, patients with previous experience of oral
anticoagulation, patients who did not have a prescription for rivaroxaban or
warfarin within 7 days of VTE, and patients who redeemed prescriptions for both
rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness
outcome was recurrent VTE and primary safety outcome was major bleeding. We used
propensity matching and Cox regression to compare rates of the outcomes with
rivaroxaban versus standard treatment. RESULTS: From Dec 9, 2011, to Feb 28,
2016, we identified 29 963 patients with incident VTE. After exclusion, we
identified 1734 propensity-matched patients given rivaroxaban (1751 before
propensity matching) and 2945 propensity-matched patients given warfarin. The
rate of recurrent VTE at 6 months' follow-up was 9.9 incidents per 100 person
years with rivaroxaban versus 13.1 incidents per 100 person-years with warfarin,
yielding a hazard ratio (HR) of 0.74 (95% CI 0.56-0.96). The rate of major
bleeding was 2.4 per 100 person-years at 6 months in rivaroxaban users versus 2.0
in warfarin users (HR 1.19, 95% CI 0.66-2.13). INTERPRETATION: In this clinical
practice setting, rivaroxaban in patients with unprovoked VTE was associated with
reduced risk of recurrent VTE compared with standard treatment, without
compromising safety. FUNDING: Obel Family Foundation.
PMID- 28411121
TI - Issues raised by the incidence and survival of childhood cancers.
PMID- 28411122
TI - The lure and pitfalls of administrative health registers.
PMID- 28411124
TI - M3 muscarinic acetylcholine receptor facilitates the endocytosis of mu opioid
receptor mediated by morphine independently of the formation of heteromeric
complexes.
AB - Morphine inefficiency to induce the internalization of mu opioid (MOP) receptors
observed in numerous experimental models constitutes a paradigm of G-protein
coupled receptor (GPCR) functional selectivity. We recently described that
activation of Galphaq/11 proteins through 5-HT2A serotonin receptors co-expressed
in the same cells facilitates MOP receptor endocytosis promoted by morphine. In
order to explore whether a different Galphaq/11 coupled GPCR would emulate this
effect, a double stable Flp-In T-REx HEK293 cell line permanently expressing MOP
YFP receptors along with FLAG-M3-Cerulean receptors expressed in an inducible
manner was generated. Fluorescence microscopy examination of these cells revealed
a co-distribution of both receptors mainly compartmentalized in plasma membrane.
Concurrent stimulation with carbachol and morphine promoted MOP receptor
internalization, desensitization and down-regulation and this facilitation was
not dependent on PKC activation. Co-immunoprecipitation experiments demonstrated
that FLAG-M3-Cerulean/MOP-YFP receptors interact forming heteromeric complexes in
a time depending manner, i.e. the strongest interaction was detected after 96h of
FLAG-M3-Cerulean induced expression. Under these experimental conditions,
treatment of cells with carbachol plus morphine resulted in the internalization
of both receptors within separated endocytic vesicles as visualized by confocal
microscopy. This trafficking segregation observed for FLAG-M3-Cerulean and MOP
YFP receptors upon agonist stimulation suggests that this protein-protein
interaction presents temporal and dynamic properties. Moreover, MOP-YFP receptor
internalization facilitated by FLAG-M3-Cerulean receptors is independent of the
constitution of heteromeric complexes.
PMID- 28411123
TI - The lens growth process.
AB - The factors that regulate the size of organs to ensure that they fit within an
organism are not well understood. A simple organ, the ocular lens serves as a
useful model with which to tackle this problem. In many systems, considerable
variance in the organ growth process is tolerable. This is almost certainly not
the case in the lens, which in addition to fitting comfortably within the
eyeball, must also be of the correct size and shape to focus light sharply onto
the retina. Furthermore, the lens does not perform its optical function in
isolation. Its growth, which continues throughout life, must therefore be
coordinated with that of other tissues in the optical train. Here, we review the
lens growth process in detail, from pioneering clinical investigations in the
late nineteenth century to insights gleaned more recently in the course of cell
and molecular studies. During embryonic development, the lens forms from an
invagination of surface ectoderm. Consequently, the progenitor cell population is
located at its surface and differentiated cells are confined to the interior. The
interactions that regulate cell fate thus occur within the obligate ellipsoidal
geometry of the lens. In this context, mathematical models are particularly
appropriate tools with which to examine the growth process. In addition to
identifying key growth determinants, such models constitute a framework for
integrating cell biological and optical data, helping clarify the relationship
between gene expression in the lens and image quality at the retinal plane.
PMID- 28411125
TI - Hypersociability in the Angelman syndrome mouse model.
AB - Deletions and reciprocal triplications of the human chromosomal 15q11-13 region
cause two distinct neurodevelopmental disorders. Maternally-derived deletions or
inactivating mutations of UBE3A, a 15q11-13 gene expressed exclusively from the
maternal allele in neurons, cause Angelman syndrome, characterized by
intellectual disability, motor deficits, seizures, and a characteristic increased
social smiling, laughing, and eye contact. Conversely, maternally-derived
triplications of 15q11-13 cause a behavioral disorder on the autism spectrum with
clinical features that include decreased sociability that we recently
reconstituted in mice with Ube3a alone. Based on the unique sociability features
reported in Angelman syndrome and the repressed sociability observed when Ube3a
gene dosage is increased, we hypothesized that mice with neuronal UBE3A loss that
models Angelman syndrome would display evidence of hypersocial behavior. We
report that mice with maternally-inherited Ube3a gene deletion (Ube3amKO) have a
prolonged preference for, and interaction with, social stimuli in the three
chamber social approach task. By contrast, interactions with a novel object are
reduced. Further, ultrasonic vocalizations and physical contacts are increased in
male and female Ube3amKO mice paired with an unfamiliar genotype-matched female.
Single housing wild type mice increased these same social behavior parameters to
levels observed in Ube3amKO mice where this effect was partially occluded. These
results indicate sociability is repressed by social experience and the endogenous
levels of UBE3A protein and suggest some social behavioral features observed in
Angelman syndrome may reflect an increased social motivation.
PMID- 28411126
TI - Low interleukin-2 concentration favors generation of early memory T cells over
effector phenotypes during chimeric antigen receptor T-cell expansion.
AB - BACKGROUND: Adoptive T-cell therapy offers new options for cancer treatment.
Clinical results suggest that T-cell persistence, depending on T-cell memory,
improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is
not straightforward because it drives effector T-cell differentiation but does
not promote the formation of T-cell memory. We have developed a cost-effective
expansion protocol for chimeric antigen receptor (CAR) T cells with an early
memory phenotype. METHODS: Lymphocytes were transduced with third-generation
lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of
altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20
days) on the phenotype of the T-cell products were analyzed. RESULTS: High IL-2
levels led to a decrease in overall generation of early memory T cells by both
decreasing central memory T cells and augmenting effectors. T memory stem cells
(TSCM, CD95+CD45RO-CD45RA+CD27+) were present variably during T-cell expansion.
However, their presence was not IL-2 dependent but was linked to expansion
kinetics. CD19-CAR T cells generated in these conditions displayed in vitro
antileukemic activity. In summary, production of CAR T cells without any cytokine
supplementation yielded the highest proportion of early memory T cells, provided
a 10-fold cell expansion and the cells were functionally potent. DISCUSSION: The
number of early memory T cells in a T-cell preparation can be increased by simply
reducing the amount of IL-2 and limiting the length of T-cell expansion,
providing cells with potentially higher in vivo performance. These findings are
significant for robust and cost-effective T-cell manufacturing.
PMID- 28411119
TI - Worldwide comparison of survival from childhood leukaemia for 1995-2009, by
subtype, age, and sex (CONCORD-2): a population-based study of individual data
for 89 828 children from 198 registries in 53 countries.
AB - BACKGROUND: Global inequalities in access to health care are reflected in
differences in cancer survival. The CONCORD programme was designed to assess
worldwide differences and trends in population-based cancer survival. In this
population-based study, we aimed to estimate survival inequalities globally for
several subtypes of childhood leukaemia. METHODS: Cancer registries participating
in CONCORD were asked to submit tumour registrations for all children aged 0-14
years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009,
and followed up until Dec 31, 2009. Haematological malignancies were defined by
morphology codes in the International Classification of Diseases for Oncology,
third revision. We excluded data from registries from which the data were judged
to be less reliable, or included only lymphomas, and data from countries in which
data for fewer than ten children were available for analysis. We also excluded
records because of a missing date of birth, diagnosis, or last known vital
status. We estimated 5-year net survival (ie, the probability of surviving at
least 5 years after diagnosis, after controlling for deaths from other causes
[background mortality]) for children by calendar period of diagnosis (1995-99,
2000-04, and 2005-09), sex, and age at diagnosis (<1, 1-4, 5-9, and 10-14 years,
inclusive) using appropriate life tables. We estimated age-standardised net
survival for international comparison of survival trends for precursor-cell acute
lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). FINDINGS: We
analysed data from 89 828 children from 198 registries in 53 countries. During
1995-99, 5-year age-standardised net survival for all lymphoid leukaemias
combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8%
(81.6-92.0) in Austria. International differences in 5-year survival for
childhood leukaemia were still large as recently as 2005-09, when age
standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8
61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for
AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German
registries. Survival from precursor-cell ALL was very close to that of all
lymphoid leukaemias combined, with similar variation. In most countries, survival
from AML improved more than survival from ALL between 2000-04 and 2005-09.
Survival for each type of leukaemia varied markedly with age: survival was
highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than
1 year). There was no systematic difference in survival between boys and girls.
INTERPRETATION: Global inequalities in survival from childhood leukaemia have
narrowed with time but remain very wide for both ALL and AML. These results
provide useful information for health policy makers on the effectiveness of
health-care systems and for cancer policy makers to reduce inequalities in
childhood cancer survival. FUNDING: Canadian Partnership Against Cancer, Cancer
Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK, US
Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research
foundation, Swiss Cancer League, and the University of Kentucky.
PMID- 28411127
TI - Preventing false-negatives in the in vitro skin sensitization testing of acid
anhydrides using interleukin-8 release assays.
AB - In vitro safety tests may be used as replacements for animal tests owing to their
accuracy and high-throughput performance. However, several in vitro skin
sensitization tests produce false-negative results such as acid anhydride. Here,
we investigated the relationship between false-negative results of acid anhydride
and its hydrolysis by aqueous vehicle. Differences in the pattern of hydrolysis
for phthalic anhydride (PAH) due to addition of 1 drop of stock solution of PAH
in liquid paraffin (LP) dispersion medium and PAH in DMSO were analyzed in a cell
free system. The results showed that use of LP dispersion medium stabilized the
concentration of PAH in water over 5min by sustained-release, although almost all
PAH converted to phthalic acid in water within 5min using DMSO. Additionally,
treatment of THP-1 cells with PAH and phthalic acid using LP dispersion medium
for 5min resulted in a 32-fold increase in IL-8 release for PAH as compared with
that in the vehicle control. In contrast, for PAH using aqueous vehicle and
phthalic acid using LP dispersion medium, there were no significant increases in
IL-8 release. Similarly, using LP dispersion medium, trimellitic anhydride
significantly increased IL-8 release was observed.
PMID- 28411128
TI - The effects of experimental gestational hypertension on maternal blood pressure
and fluid intake and pre-weanling hypothalamic neuronal activity.
AB - To examine the fetal programming effects of maternal hypertension, natriophilia
and hyperreninemia [experimentally induced in rats by partial inter-renal aortic
ligature (PAL) prior to mating] fos immunoreactivity was studied in 6-day-old
offspring of PAL and control mothers. The purposes of the present set of
experiments were twofold. The first was to characterize the effects of PAL on the
mother's arterial blood pressure and intake of salt (1.8% NaCl solution) and
water over the course of gestation. Second, was to study the pattern of neuronal
activation in key brain areas of 6-day-old offspring treated with the dipsogen
isoproterenol that were from PAL and control mothers. Beta-adrenergic receptor
agonist-treated pups allowed the determination whether there were neuroanatomical
correlates within the neural substrates controlling thirst and the enhanced water
intake evidenced by the isoproterenol treated pups of PAL mothers. Hydromineral
ingestive behavior along with blood pressure and heart rate of PAL (M-PAL) and
control (M-sPAL) dams throughout gestation was studied. Higher salt and water
intakes along with blood pressures and heart rates were found during gestation
and lactation in the M-PAL group. Maternal PAL evoked significantly increased
isoproterenol-elicited Fos staining in brain regions (e.g. subfornical organ,
organum vasculosum of the lamina terminalis, supraoptic nucleus, hypothalamic
paraventricular nucleus and median preoptic nucleus) of 6-day-old pups, which is
the age of animals shown enhanced thirst responses in PAL offspring. These
results indicate that PAL is compatible with pregnancy, producing a sustained
increase in blood pressure and heart rate, along with increased water and salt
intake. The present study demonstrates that the neural substrates involved in
cardiovascular homeostasis and fluid balance in adult rats are responsive in six
day-old rats, and can be altered by fetal programming.
PMID- 28411129
TI - Detection of a novel highly pathogenic H7 influenza virus by duplex real-time
reverse transcription polymerase chain reaction.
AB - On February 19, 2017, China announced that the mutant H7N9 virus appeared in
human cases, which showed molecular characteristic of highly pathogenic virus for
poultry. In this study, a duplex real-time reverse transcription polymerase chain
reaction (rRT-PCR) assay was developed for distinguish between highly pathogenic
H7 virus and low pathogenic H7 virus. The sensitivity, specificity, stability and
conformance tests were conducted for this method. The data showed that the new
method is sensitive. The minimum detection limit for the RNA of highly pathogenic
H7 virus is 0.0052fg and the minimum detection limit for the RNA of low
pathogenic H7 virus is 0.36fg. The method gave specific results in detecting
novel highly pathogenic H7 virus and will play an important role in the rapid
identification of novel highly pathogenic H7 virus.
PMID- 28411131
TI - Influence of N-acetyl cysteine on beta-amyloid-induced Alzheimer's disease in a
rat model: A behavioral and electrophysiological study.
AB - Alzheimer's disease is an age-related neurodegenerative disorder characterized by
a progressive decline in cognitive function due to the extracellular accumulation
and deposition of beta-amyloid peptide (Abeta). The purpose of this study was to
evaluate the protective effect of N-acetyl cysteine (NAC) on learning and memory
in an Abeta-induced Alzheimer's disease model in adult male rats, using
behavioral and electrophysiological methods Thirty-five rats were divided into
five groups: control, sham-operated, Abeta, Abeta+NAC (1-14days), and Abeta+NAC
(14-28days). Learning and memory were evaluated behaviorally using the passive
avoidance test and electrophysiologically by assessing hippocampal long-term
potentiation, a cellular mechanism of learning and memory. Intrahippocampal Abeta
injections reduced step-through latency in the passive avoidance test, and
decreased both the amplitude of hippocampal neuron population spikes and the
slope of excitatory postsynaptic potentials, compared to the sham and control
groups. Administration of NAC in rats receiving Abeta alleviated the Abeta
induced deficits in comparison to the Abeta-only group. The results of this study
suggest that NAC shows potential for treatment of Alzheimer's disease.
PMID- 28411130
TI - IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor
resistant breast cancer in vivo by JAK/STAT-mediated induction of p21.
AB - Interferon induced transmembrane protein 1 (IFITM1) belongs to a family of
interferon stimulated genes (ISGs) that is associated with tumor progression and
DNA damage resistance; however, its role in endocrine resistance is not known.
Here, we correlate IFITM1 expression with clinical stage and poor response to
endocrine therapy in a tissue microarray consisting of 94 estrogen receptor (ER)
positive breast tumors. IFITM1 overexpression is confirmed in the AI-resistant
MCF-7:5C cell line and not found in AI-sensitive MCF-7 cells. In this study, the
orthotopic (mammary fat pad) and mouse mammary intraductal (MIND) models of
breast cancer are used to assess tumor growth and invasion in vivo. Lentivirus
mediated shRNA knockdown of IFITM1 in AI-resistant MCF-7:5C cells diminished
tumor growth and invasion and induced cell death, whereas overexpression of
IFITM1 in wild-type MCF-7 cells promoted estrogen-independent growth and enhanced
their aggressive phenotype. Mechanistic studies indicated that loss of IFITM1 in
MCF-7:5C cells markedly increased p21 transcription, expression and nuclear
localization which was mediated by JAK/STAT activation. These findings suggest
IFITM1 overexpression contributes to breast cancer progression and that targeting
IFITM1 may be therapeutically beneficial to patients with endocrine-resistant
disease.
PMID- 28411134
TI - An unusual localization for an usual tumor.
PMID- 28411132
TI - Methyl jasmonate attenuates memory dysfunction and decreases brain levels of
biomarkers of neuroinflammation induced by lipopolysaccharide in mice.
AB - Neuroinflammation plays a central role in the etiology and progression of
Alzheimer's disease (AD), a neurodegenerative disorder, characterized by a
gradual loss of memory functions. Thus, it has been proposed that agents that
could reduce inflammatory processes in AD brains might be useful for the
treatment of the disease. Methyl jasmonate (MJ) is a bioactive compound, which
has been reported to exhibit anti-amnesic and in vitro anti-inflammatory
activities. In this study, we further examine its effects on the brain levels of
biomarkers of neuroinflammation in lipopolysaccharide (LPS)-induced memory
deficits in mice. Mice (n=6) were pretreated intraperitoneally with MJ (10
40mg/kg), donepezil (DP) (1mg/kg) or vehicle (10mL/kg) for 30min prior to
injection of LPS (250MUg/kg, i.p) daily for 7days. Thirty minutes after LPS
administration on day 7, memory function was assessed using Y-maze test. After Y
maze test, the levels of biomarkers of neuroinflammation: prostaglandin E2
(PGE2), tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta)
were estimated in brain tissue homogenates using ELISA. Expressions of positive
cells of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), nuclear
factor kappa B (NF-kappaB) and amyloid-beta (Abeta) in the prefrontal cortex were
also assessed using immunohistochemistry technique. Our data showed that MJ (10,
20 and 40mg/kg) significantly (p<0.05) reversed LPS-induced memory deficits in
mice. The increased brain levels of PGE2, TNFalpha and IL1beta in LPS-treated
mice were significantly (p<0.05) reduced by MJ indicating anti-neuroinflammatory
activity. MJ also suppressed the expression of COX2, iNOS and NFkappaB, which
further suggest anti-neuroinflammation. The increased brain level of Abeta in LPS
treated mice was significantly (p<0.05) suppressed by MJ suggesting anti
amyloidogenesis-like effect. Our present data showed that MJ attenuated LPS
induced memory dysfunction via mechanisms involving inhibition of pro
inflammatory mediators and beta-amyloid generation in mice.
PMID- 28411133
TI - Clinical significance of fibromyalgia syndrome in different rheumatic diseases:
Relation to disease activity and quality of life.
AB - OBJECTIVE: To describe the frequencies of fibromyalgia syndrome (FMS) in various
rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus
(SLE), systemic sclerosis (SSc) and Behcets disease (BD) patients and to study
the relation to clinical manifestations and quality of life (QoL). PATIENTS AND
METHODS: 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding
healthy controls were included. Disease activity was assessed using disease
activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI),
modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL
was also recorded. Severity in FMS cases was estimated using the revised
Fibromyalgia Impact Questionnaire score. RESULTS: In the RA, SLE, SSc and BD
patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to
2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was
significantly higher in those with FMS (p=0.009) and significantly correlated
with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale
(p=0.012). The QoL scale in those with FMS was significantly worse (62.3+/-7.9)
compared to those without (71.7+/-14.4) (p=0.023). In SLE patients, The WPI and
SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049
and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the
SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated
(p=0.03). CONCLUSION: Fibromyalgia syndrome is more frequent in rheumatic
diseases, could be related to the disease activity in RA and BD patients and to
thrombosis in SLE and affected the QoL in RA.
PMID- 28411135
TI - Silent sinus syndrome: A traumatic case.
AB - INTRODUCTION: Silent sinus syndrome is an unusual cause of progressive
enophthalmos and hypoglobus due to atelectasia of the maxillary sinus associated
with osteolysis of the orbital floor. This syndrome is classically idiopathic,
but the term is also used to describe traumatic or iatrogenic (surgical orbital
decompression) cases. CASE REPORT: We report the case of a 33-year-old man who
presented with a left orbital trauma without functional disorder. Computed
tomography (CT) scan revealed a nondisplaced fracture of the left orbital floor.
No surgical indication was made. Three months later, the patient presented with
progressive enophthalmos. CT revealed a complete lysis of the left orbital floor
and a left maxillary sinus atelectasia. DISCUSSION: The original nondisplaced
fracture of the orbital floor was not responsible for enophthalmos but the
associated fracture of the left uncinate process that induced the closure of the
left maxillary sinus infundibulum. This induced in turn hypoventilation of the
sinus and a left orbital floor lysis. Treatment consisted in surgical opening of
the maxillary sinus ostium and reconstruction of the orbital floor.
PMID- 28411136
TI - Augmentation of keratinized gingiva around dental implants.
AB - To date, there is no general consensus with respect to the amount of soft-tissue
volume needed for esthetic and functional purposes on the buccal aspect of dental
implants. Numerous studies have investigated the relationship between the width
of keratinized mucosa and the health of peri-implant tissues. Our purpose was to
discuss about the necessity of keratinized tissue to maintain the peri-implant
health and to report clinical efficacy of different techniques used to increase
the keratinized tissue around dental implants.
PMID- 28411137
TI - GOSPEL 3: Management of gout by primary-care physicians and office-based
rheumatologists in France in the early 21st century - comparison with 2006 EULAR
Recommendations.
AB - INTRODUCTION: In 2006, recommendations about the management of gout were issued
by the European League Against Rheumatism (EULAR). The objective of this work was
to compare these recommendations to practice patterns of physicians working in
private practices in France. METHOD: In a prospective multicenter nationwide
study conducted in France, a random sample of primary-care physicians (PCPs) and
private-practice rheumatologists (PPRs) was taken in 2009. Each physician
included 2 consecutive patients with gout. Each patient was evaluated twice at an
interval of 3-6months. Information on EULAR 2006 management modalities were
collected in a standardized manner. RESULTS: Of 1003 patients, 771 were evaluated
twice. Allopurinol was prescribed to 75.1% of patients in all and was initiated
at the first study visit in 44 patients, among whom 19 (43.2%) 19 patients
received the recommended starting dosage of 100mg/day. Colchicine therapy to
prevent flares was prescribed to 74.3% of patients. Of the 522 patients on
allopurinol therapy at the first visit, only 34.5% had serum uric acid
levels<=360MUmoL/L (mean dosage, 173 mg/day). Excessive dietary intake by
patients who were overweight or obese was recorded in 31.5% of patients seen by
PCPs and in 19.7% of those seen by OBRs. This finding prompted the delivery of
nutritional advice to 45.8% of patients. Discontinuation of excessive alcohol
intake was recommended to only 10% of patients. Diuretic therapy discontinuation
was feasible in 175 patients but was recommended in only 7 patients. CONCLUSION:
Differences between practice patterns and 2006 EULAR recommendations were
identified. Simplifying the recommendations and teaching them during medical
training and continued medical education may deserve consideration.
PMID- 28411138
TI - Acute lumbar radiculopathy caused by an epidural pseudocyst associated to an
intraosseous pneumatocyst.
PMID- 28411139
TI - The QUIDAM study: Hydroquinidine therapy for the management of Brugada syndrome
patients at high arrhythmic risk.
AB - BACKGROUND: Although the implantable cardioverter-defibrillator (ICD) remains the
main therapy for Brugada syndrome (BrS), it does not reduce life-threatening
ventricular arrhythmia. Based on pathophysiologic mechanisms, hydroquinidine (HQ)
has been suggested for effective prevention of arrhythmia. OBJECTIVE: The purpose
of this study was to provide evidence-based data supporting HQ use to prevent
life-threatening ventricular arrhythmia in high-risk patients with BrS. METHODS:
We performed a prospective multicenter randomized (HQ vs placebo) double-blind
study with two 18-month crossover phases in patients with BrS and implanted with
an ICD. RESULTS: Among the 50 patients enrolled (mean age 47.0 +/- 11.4 years, 42
[84%] male), 26 (52%) fully completed both phases. Thirty-four (68%) presented HQ
related side effects, mainly gastrointestinal, which led to discontinuation of
the therapy in 13 (26%). HQ lengthened the QTc interval (409 +/- 32 ms vs 433 +/-
37 ms; P = .027) and increased repolarization dispersion as evaluated by Tpe max
in precordial leads (89 +/- 15 ms vs 108 +/- 27 ms; P <.0001) with no significant
changes in J-point elevation. During the 36-month follow-up, 1 appropriate ICD
shock (0.97% event per year), 1 self-terminating ventricular fibrillation, and 1
inappropriate ICD shock occurred under placebo therapy. No arrhythmic events were
reported under HQ therapy. CONCLUSION: Although HQ seems to be effective in
preventing life-threatening ventricular arrhythmia, it could not be an
alternative for ICD implantation. Its frequent side effects greatly reduce its
probable compliance and therefore do not reveal a significant effect. HQ
increases repolarization dispersal with no changes in BrS pattern, which could
indicate a more complex action of HQ than its Ito blocking effect alone.
PMID- 28411141
TI - Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic
bacterial resistance: In vitro antibacterial study.
AB - Despite the fact that carbapenems (powerful beta-lactams antibiotics) were able
to fight serious infectious diseases, nowadays the spread of carbapenems
resistant bacteria is considered the main challenge in antibacterial therapy. In
this study, we focused on evaluating the surface conjugation of carbapenems
(imipenem and meropenem) with gold nanoparticles as a delivering strategy to
specifically and safely maximize their therapeutic efficacy while destroying the
developing resistance of the pathogens. Different particle size formulae (35, 70
and 200nm) were prepared by citrate reduction method. The prepared nanoparticles
were functionalized with imipenem (Ipm) or meropenem (Mem) and physico-chemically
characterized for loading efficiency, particle size, morphology, and in-vitro
release. The antibacterial efficacy was also evaluated against carbapenems
resistant Gram-negative bacteria isolated from infected human, through measuring
the minimum inhibitory concentration and antibiotic kill test. All the obtained
gold nanoparticles showed a distinct nano-size with loading efficiency up to 72%
and 74% for Ipm and Mem, respectively. The conjugation and physico-chemical
stability of the formulated carbapenems were confirmed by FTIR and X-RPD.
Diffusion driven release behavior was observed for both Ipm and Mem from all of
the loaded gold nanoparticles. For both Ipm and Mem, formula with 35nm diameter
showed the most significant enhancement in antibacterial activity against all the
selected isolates including Klebsiella pneumoniae, Proteus mirabilis and
Acinteobacter baumanii. Ipm loaded Gold nanoparticles demonstrated decrease in
the MIC of Ipm down to four folds, whereas, Mem loaded gold nanoparticles showed
decrease in the MIC of Mem down to three folds on the tested bacterial isolates.
Based on these results, the formulation of carbapenems-loaded gold nanoparticles
demonstrated to be a promising nano-size delivery vehicle for improving the
therapeutic activity and destroying the bacterial resistance for carbapenems.
PMID- 28411140
TI - Batf3-dependent CD8alpha+ Dendritic Cells Aggravates Atherosclerosis via Th1 Cell
Induction and Enhanced CCL5 Expression in Plaque Macrophages.
AB - Dendritic cells (DCs) play an important role in controlling T cell-mediated
adaptive immunity in atherogenesis. However, the role of the basic leucine zipper
transcription factor, ATF-like 3 (Batf3)-dependent CD8alpha+ DC subset in
atherogenesis remains unclear. Here we show that Batf3-/-Apoe-/- mice, lacking
CD8alpha+ DCs, exhibited a significant reduction in atherogenesis and T help 1
(Th1) cells compared with Apoe-/- controls. Then, we found that CD8alpha+ DCs
preferentially induce Th1 cells via secreting interleukin-12 (IL-12), and that
the expression of interferon-gamma (IFN-gamma)or chemokine (C-C motif) ligand 5
(CCL5) in aorta were significantly decreased in Batf3-/-Apoe-/- mice. We further
demonstrated that macrophages were the major CCL5-expressing cells in the plaque,
which was significantly reduced in Batf3-/-Apoe-/- mice. Furthermore, we found
CCL5 expression in macrophages was promoted by IFN-gamma. Finally, we showed that
Batf3-/-Apoe-/- mice displayed decreased infiltration of leukocytes in the
plaque. Thus, CD8alpha+ DCs aggravated atherosclerosis, likely by inducing Th1
cell response, which promoted CCL5 expression in macrophages and increased
infiltration of leukocytes and lesion inflammation.
PMID- 28411142
TI - Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory
drug nimesulide.
AB - Understanding the phase behavior of active pharmaceutical ingredients is
important for formulations of dosage forms and regulatory reasons. Nimesulide is
an anti-inflammatory drug that is known to exhibit dimorphism; however up to now
its stability behavior was not clear, as few thermodynamic data were available.
Therefore, calorimetric melting data have been obtained, which were found to be
TI-L=422.4+/-1.0K, DeltaI->LH=117.5+/-5.2Jg-1,TII-L=419.8+/-1.0K and DeltaII
>LH=108.6+/-3.3Jg-1. In addition, vapor-pressure data, high-pressure melting
data, and specific volumes have been obtained. It is demonstrated that form II is
intrinsically monotropic in relation to form I and the latter would thus be the
best polymorph to use for drug formulations. This result has been obtained by
experimental means, involving high-pressure measurements. Furthermore, it has
been shown that with very limited experimental and statistical data, the same
conclusion can be obtained, demonstrating that in first instance topological
pressure-temperature phase diagrams can be obtained without necessarily measuring
any high-pressure data. It provides a quick method to verify the phase behavior
of the known phases of an active pharmaceutical ingredient under different
pressure and temperature conditions.
PMID- 28411143
TI - Proposed diagnostic criteria for the case definition of amniotic fluid embolism
in research studies.
PMID- 28411144
TI - Management of sexuality, intimacy, and menopause symptoms in patients with
ovarian cancer.
AB - Issues of sexuality, intimacy, and early menopause significantly impact the
quality of life of patients following the diagnosis and treatment of ovarian
cancer. These are undertreated problems. Successful treatment requires the
provider's awareness of the problem, ability to identify it, and willingness to
treat it. Unfortunately many providers do not address these issues in the
pretreatment or perioperative period. Furthermore, patients do not often alert
their providers to their symptoms. While systemic hormone therapy may improve
many of the issues, they are not appropriate for all patients given their action
on estrogen receptors. However, other nonhormonal treatments exist including
selective serotonin reuptake inhibitors, antiepileptics, natural remedies, and
pelvic floor physical therapy. In addition psychological care and the involvement
of the partner can be helpful in managing the sexual health concerns of these
patients. At the time of diagnosis or at initial consultation, women should be
informed of the potential physiologic, hormonal, and psychosocial effects of
ovarian cancer on sexuality and that there is a multimodal approach to dealing
with symptoms.
PMID- 28411145
TI - Current and future role of genetic screening in gynecologic malignancies.
AB - The world of hereditary cancers has seen exponential growth in recent years.
While hereditary breast and ovarian cancer and Lynch syndrome account for the
majority of mutations encountered by gynecologists, newly identified deleterious
genetic mutations continue to be unearthed with their associated risks of
malignancies. However, these advances in genetic cancer predispositions then
force practitioners and their patients to confront the uncertainties of these
less commonly identified mutations and the fact that there is limited evidence to
guide them in expected cancer risk and appropriate risk-reduction strategies.
Given the speed of information, it is imperative to involve cancer genetics
experts when counseling these patients. In addition, coordination of screening
and care in conjunction with specialty high-risk clinics, if available, allows
for patients to have centralized management for multiple cancer risks under the
guidance of physicians with experience counseling these patients. The objective
of this review is to present the current literature regarding genetic mutations
associated with gynecologic malignancies as well to propose screening and risk
reduction options for these high-risk patients.
PMID- 28411146
TI - Reply.
PMID- 28411147
TI - 20-Year Trend of CVD Risk Factors: Urban and Rural National Capital Region of
India.
AB - BACKGROUND: The World Health Organization and the Government of India have set
targets to reduce burden of noncommunicable diseases. Information on population
level trend of risk factors would provide insights regarding the possibility of
achieving them. OBJECTIVE: This study aimed to determine the population trends of
cardiovascular disease risk factors in the National Capital Region of Delhi over
2 decades. METHODS: Two representative cross-sectional surveys were conducted
among men and women ages 35 to 64 years, residing in the urban and rural areas
(survey 1 [1991 to 1994] and survey 2 [2010 to 2012]) using similar methodology.
The urban sample was collected from the Municipal Corporation of Delhi, and the
rural sample was from the Ballabgarh block of the adjoining state of Haryana. A
total of 3,048 and 2,052 subjects of urban areas and 2,487 and 1,917 subjects of
rural areas were surveyed in surveys 1 and 2, respectively. Behavioral (smoking
and alcohol use), physical (overweight, abdominal obesity, and raised blood
pressure), and biochemical risk factors (raised fasting blood glucose and raised
total cholesterol) were measured using standard tools. RESULTS: Urban and rural
prevalence of overweight, alcohol use, raised blood pressure, and blood glucose
increased with increases in age-standardized mean body mass index (urban: 24.4 to
26.0 kg/m2; rural: 20.2 to 23.0 kg/m2), systolic blood pressure (urban: 121.2 to
129.8 mm Hg; rural: 114.9 to 123.1 mm Hg), diastolic blood pressure (urban: 74.3
to 83.9 mm Hg; rural: 73.1 to 82.3 mm Hg), and fasting glucose (urban: 101.2 to
115.3 mg/dl; rural: 83.9 to 103.2 mg/dl). The smoking prevalence increased in the
rural male population. Raised total cholesterol declined in urban and increased
significantly in rural populations. CONCLUSIONS: The study indicates an overall
worsening of population levels of all cardiovascular disease risk factors in
National Capital Region over past 20 years, though some signs of stabilization
and reversal are seen in urban Delhi.
PMID- 28411148
TI - Behavioural characterization of AnkyrinG deficient mice, a model for ANK3 related
disorders.
AB - ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in
several different isoforms in many tissues. A unique serine-rich domain and tail
domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the
axon initial segment and nodes of Ranvier of myelinated neurons. At these sites,
AnkG is a master regulator, coordinating the strict clustering of components
necessary for proper action potential initiation and propagation along the axon.
These components include voltage-gated sodium channels, potassium channels and
members of the L1 cell adhesion molecule family. Genetic variation in the ANK3
gene has been linked to a range of neuropsychiatric and neurodevelopmental
disorders in human, including schizophrenia, bipolar disorder, intellectual
disability and autism spectrum disorders. Here, we study the effect of reduced
expression of the large isoforms of Ank3 on cognition and behaviour using a
heterozygous knockout mouse model. In three independent behavioural tests, being
the open field test, elevated plus maze and social interaction test, we found
evidence for increased anxiety in our Ank3 mouse model. Besides, we observed
specific neuroanatomical defects in heterozygous knockout mice, including a
smaller cingulate cortex, granular retrosplenial cortex, primary motor cortex and
fimbria of the hippocampus.
PMID- 28411149
TI - Neuroprotective effect of three caffeic acid derivatives via ameliorate oxidative
stress and enhance PKA/CREB signaling pathway.
AB - This study was conducted to elucidate the neuroprotective effect of caffeic acid
phenethyl ester (CAPE), (R)-2-Hydroxy-3-(3,4-dihydroxyphenyl) propionic acid
(Danshensu) and Curcumin, three caffeic acid derivatives which are contained in
fruits, grains and certain dietary supplements. Our results showed that these
compounds significantly attenuated H2O2-induced toxicity in PC12 cells in a dose
dependent manner. Furthermore, these compounds significantly improved the
behavioral performance of d-gal-treated mice in both step-down avoidance test and
Morris water maze test. Biochemical examination and western blot analysis showed
that these compounds could ameliorate oxidative stress and facilitate activation
of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB)
pathway. Its beneficial effects may partly relate to enhancing the activity of
endogenous antioxidant enzymes and modulating the PKA/CREB signaling pathway.
Furthermore, our results also indicated that the presence of 3, 4-dihydroxyphenyl
groups in A ring may enhance their neuroprotective activity.
PMID- 28411150
TI - Comparative diagnostic efficacy of recombinant LLO and PI-PLC-based ELISAs for
detection of listeriosis in animals.
AB - The present study for the first time evaluates the serodiagnostic efficacy of two
recombinant antigens namely, listeriolysin O (rLLO) and phosphatidyl-inositol
phospholipase C (rPI-PLC). Indirect ELISA with the above recombinant antigens was
used on samples collected from bovines (n=106), goats (n=138) and pigs (n=92)
having either a history of abortion, emaciation and/or apparently healthy
animals. Isolation of Listeria was attempted from the blood samples using USDA
FSIS method. On screening of test sera by rLLO-based ELISA, antibodies against
anti-listeriolysin O (ALLO) were observed in goats (22.46%), bovines (15.10%) and
pigs (16.31%). As advocated, after adsorption of positive serum samples with
streptolysin O (SLO), the seropositivity for ALLO was marginally reduced (p>0.05)
in goats (21.73%) and bovines (10.38%), whereas, in pigs the reduction (5.43%)
was significant (p<0.05). On the contrary, rPI-PLC-based ELISA revealed higher
non-specific seropositivity for antilisterial antibodies in goats (45.65%),
bovines (31.13%) and pigs (8.69%). Further, on comparing the seropositivity with
isolation rate, of the 16 animals that were culturally-positive for L.
monocytogenes, 15 showed ALLO positivity in unadsorbed as well as SLO-adsorbed
sera by rLLO-based ELISA, however, rPI-PLC-based ELISA could detect
seropositivity in only 5 animals. Moreover, rPI-PLC-based ELISA also showed
seropositivity in those animals (7/30) that were culturally positive for other
Listeria spp. In conclusion, rLLO can serve as a better antigen than rPI-PLC in
ELISA for the serodiagnosis of listeriosis in animals; however, prior adsorption
of test sera with SLO is required to avoid false positive results.
PMID- 28411151
TI - Enabling a sustainable and prosperous future through science and innovation in
the bioeconomy at Agriculture and Agri-Food Canada.
AB - Science and innovation are important components underpinning the agricultural and
agri-food system in Canada. Canada's vast geographical area presents diverse,
regionally specific requirements in addition to the 21st century agricultural
challenges facing the overall sector. As the broader needs of the agricultural
landscape have evolved and will continue to do so in the next few decades, there
is a trend in place to transition towards a sustainable bioeconomy, contributing
to reducing greenhouse gas emission and our dependency on non-renewable
resources. We highlight some of the key policy drivers on an overarching national
scale and those specific to agricultural research and innovation that are
critical to fostering a supportive environment for innovation and a sustainable
bioeconomy. As well, we delineate some major challenges and opportunities facing
agriculture in Canada, including climate change, sustainable agriculture, clean
technologies, and agricultural productivity, and some scientific initiatives
currently underway to tackle these challenges. The use of various technologies
and scientific efforts, such as Next Generation Sequencing, metagenomics
analysis, satellite image analysis and mapping of soil moisture, and value-added
bioproduct development will accelerate scientific development and innovation and
its contribution to a sustainable and prosperous bioeconomy.
PMID- 28411152
TI - The origins of the bioeconomy in the European Union.
AB - This article outlines the context and circumstances that favoured the development
of a Bioeconomy Strategy in the European Union (EU) and the role played by the
different Framework programmes for Research, Technological Development and
Demonstration. Particular attention is given to the biotechnology related
programmes and more specifically to the "Cell Factory" Key Action in the 5th
Framework Programme (1998-2002). This, together with the parallel development of
a Strategy on Biotechnology in 2002, served as a solid foundation for the
creation of the, at the time, so-called Knowledge-Based Bio-Economy (KBBE). The
KBBE concept emerged in 2005, a couple of years before the launch of the 7th
Framework Programme (2007-2013). The experience accumulated over the years and
the new societal expectations triggered the EU to launch a Strategy on Bioeconomy
in 2012. This article concludes with a brief analysis of the two most important
impacts of the EU Strategy on Bioeconomy. One is the Bioeconomy dedicated
activity within the Programme Horizon 2020 (2014-2020), and the other the
creation of a public-private partnership of bio-based industries. Both the impact
of Horizon 2020 on the EU Bioeconomy Strategy and the bio-based industries public
private partnership are analysed in depth in two articles elsewhere in this
volume.
PMID- 28411154
TI - Neural mechanisms of individual differences in temporal discounting of monetary
and primary rewards in adolescents.
AB - Adolescents are generally characterized as impulsive. However, impulsivity is a
multi-dimensional construct that involves multiple component processes. Which of
these components contribute to adolescent impulsivity is currently unclear. This
study focused on the neural mechanisms underlying individual differences in
distinct components of temporal discounting (TD), i.e., the preference for
smaller immediate rewards over larger delayed rewards. Participants were 58
adolescents (12-16 years-old) who performed an fMRI TD task with both monetary
and snack rewards. Using mixed-effects modeling, we determined participants'
average impatience, and further decomposed TD choices into: 1) amount sensitivity
(unique contribution of the magnitude of the immediate reward); and 2) delay
sensitivity (unique contribution of delay duration). Adolescents' average
impatience was positively correlated with frontoparietal and ventral striatal
activity during delayed reward choices, and with ventromedial prefrontal cortex
activity during immediate reward choices. Adolescents' amount sensitivity was
positively associated with ventral striatal and dorsal anterior cingulate cortex
activity during immediate reward choices. Delay sensitivity was positively
correlated with inferior parietal cortex activity during delayed reward choices.
As expected, snacks were discounted more steeply than money, and TD of both
reward types was associated with overlapping activation in the inferior parietal
cortex. Exploring whether testosterone or estradiol were associated with TD and
its neural correlates revealed no significant associations. These findings
indicate that distinct components contribute uniquely to TD choice and that
individual differences in amount sensitivity are uniquely associated with
activation of reward valuation areas, while individual differences in delay
sensitivity are uniquely associated with activation of cognitive control areas.
PMID- 28411153
TI - Antagonism of muscarinic acetylcholine receptors in medial prefrontal cortex
disrupts the context preexposure facilitation effect.
AB - Cholinergic function plays a role in a variant of context fear conditioning known
as the context preexposure facilitation effect (CPFE; Robinson-Drummer, Dokovna,
Heroux, & Stanton, 2016). In the CPFE, acquisition of a context representation,
the context-shock association, and expression of context fear occur across
successive phases, usually 24h apart. Systemic administration of scopolamine, a
muscarinic acetylcholine receptor antagonist, prior to each phase (context
preexposure, immediate-shock training, and testing) disrupts the CPFE in juvenile
rats (Robinson-Drummer et al., 2016). Dorsal hippocampal (dHPC) cholinergic
function contributes significantly to this effect, as local infusion of
scopolamine into the dHPC prior to any individual phase of the CPFE produces a
disruption identical to systemic administration (Robinson-Drummer et al., 2016).
The current experiment extended these findings to another forebrain region
implicated in the CPFE, the medial prefrontal cortex (mPFC). Adolescent rats
received bilateral infusions of scopolamine (35MUg/side) or PBS 10min before all
three phases of the CPFE or only prior to a single phase. Intra-mPFC
administration of scopolamine prior to all three phases significantly impaired
fear conditioning suggesting that mPFC cholinergic function is necessary for
successful CPFE performance. Analyses of the individual infusion days revealed a
significant impairment of the CPFE when infusions occurred prior to preexposure
or training (i.e. immediate footshock) but not prior to testing. In total, these
findings suggests a role of mPFC cholinergic function in the acquisition and/or
consolidation of a contextual representation and the context-shock association
but not in retrieval or expression of fear memory. Implications for mPFC
involvement in contextual fear conditioning and neurological dysfunction
following neonatal alcohol exposure are discussed.
PMID- 28411155
TI - Trial timing and pattern-information analyses of fMRI data.
AB - Pattern-information approaches to fMRI data analysis are becoming increasingly
popular but few studies to date have investigated experimental design
optimization for these analyses. Here, we tested several designs that varied in
the number of trials and trial timing within fixed duration scans while
participants encoded images of animals and tools. Trial timing conditions with
fixed onset-to-onset timing ranged from slow 12-s trials with two repetitions of
each item to quick 6-s trials with four repetitions per item. We also tested a
jittered version of the quick design with 4-8s trials. We assessed the effect of
trial timing on three dependent measures: category-level (animals vs. tools)
decoding accuracy using a multivoxel pattern analysis, item-level (e.g., cat vs.
dog vs. lion) information estimates using pattern similarity analysis, and memory
effects comparing pattern similarity scores across repetitions of individual
items subsequently remembered vs. forgotten. For single trial estimates, category
decoding was equal across all trial timing conditions while item-level
information and memory effects were better detected using slow trial timing. When
modeling events on an item-by-item basis across all repetitions of a given item,
a larger number of quick, regularly spaced trials provided an advantage over
fewer slow trials for category decoding while item-level information was
comparable across conditions. Jittered and non-jittered versions of the quick
trial timing did not differ significantly in any analysis. These results will
help inform experimental design choices in future studies planning to employ
pattern-information analyses and demonstrate that design optimization guidelines
developed for univariate analyses of a few conditions are not necessarily optimal
for pattern-information analyses and condition-rich designs.
PMID- 28411156
TI - A graded tractographic parcellation of the temporal lobe.
AB - The temporal lobe has been implicated in multiple cognitive domains through
lesion studies as well as cognitive neuroimaging research. There has been a
recent increased interest in the structural and connective architecture that
underlies these functions. However there has not yet been a comprehensive
exploration of the patterns of connectivity that appear across the temporal lobe.
This article uses a data driven, spectral reordering approach in order to
understand the general axes of structural connectivity within the temporal lobe.
Two important findings emerge from the study. Firstly, the temporal lobe's
overarching patterns of connectivity are organised along two key structural axes:
medial to lateral and anteroventral to posterodorsal, mirroring findings in the
functional literature. Secondly, the connective organisation of the temporal lobe
is graded and transitional; this is reminiscent of the original work of 19th
Century neuroanatomists, who posited the existence of some regions which
transitioned between one another in a graded fashion. While regions with unique
connectivity exist, the boundaries between these are not always sharp. Instead
there are zones of graded connectivity reflecting the influence and overlap of
shared connectivity.
PMID- 28411157
TI - The separate effects of lipids and proteins on brain MRI contrast revealed
through tissue clearing.
AB - Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the
relative contribution of different biological components (e.g. lipids and
proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density,
diffusion) remains incompletely understood. This limitation can undermine the
interpretation of clinical MRI and hinder the development of new contrast
mechanisms. Here, we determine the respective contribution of lipids and proteins
to MRI contrast by removing lipids and preserving proteins in mouse brains using
CLARITY. We monitor the temporal dynamics of tissue clearance via NMR
spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared
brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased
relaxation times; and 3) diffusion rates close to free water. We conclude that
lipids, present in myelin and membranes, are a dominant source of MRI contrast in
brain tissue.
PMID- 28411158
TI - Intrinsic membrane properties and cholinergic modulation of mouse basal forebrain
glutamatergic neurons in vitro.
AB - The basal forebrain (BF) controls sleep-wake cycles, attention and reward
processing. Compared to cholinergic and GABAergic neurons, BF glutamatergic
neurons are less well understood, due to difficulties in identification. Here, we
use vesicular glutamate transporter 2 (vGluT2)-tdTomato mice, expressing a red
fluorescent protein (tdTomato) in the major group of BF glutamatergic neurons
(vGluT2+) to characterize their intrinsic electrical properties and cholinergic
modulation. Whole-cell, patch-clamp recordings were made from vGluT2+ neurons in
coronal BF slices. Most BF vGluT2+ neurons were small/medium sized (<20um),
exhibited moderately sized H-currents and had a maximal firing frequency of
~50Hz. However, vGluT2+ neurons in dorsal BF (ventral pallidum) had larger H
currents and a higher maximal firing rate (83Hz). A subset of BF vGluT2+ neurons
exhibited burst/cluster firing. Most vGluT2+ neurons had low-threshold calcium
spikes/currents. vGluT2+ neurons located in ventromedial regions of BF (in or
adjacent to the horizontal limb of the diagonal band) were strongly
hyperpolarized by the cholinergic agonist, carbachol, a finding apparently in
conflict with their increased discharge during wakefulness/REM sleep and
hypothesized role in wake-promotion. In contrast, most vGluT2+ neurons located in
lateral BF (magnocellular preoptic area) or dorsal BF did not respond to
carbachol. Our results suggest that BF glutamatergic neurons are heterogeneous
and have morphological, electrical and pharmacological properties which
distinguish them from BF cholinergic and GABAergic neurons. A subset of vGluT2+
neurons, possibly those neurons which project to reward-related areas such as the
habenula, are hyperpolarized by cholinergic inputs, which may cause phasic
inhibition during reward-related events.
PMID- 28411159
TI - In vivo visualization of connections among revised Papez circuit hubs using full
q-space diffusion spectrum imaging tractography.
AB - Structural connections among the hubs of the revised Papez circuit remain to be
elucidated in the human brain. As the original Papez circuit failed to explain
functional imaging findings, a more detailed investigation is needed to delineate
connections among the circuit's key hubs. Here we acquired diffusion spectrum
imaging (DSI) from eight normal subjects and used data from the Human Connectome
Project (HCP) to elucidate connections among hubs in the retrosplenial gyrus,
hippocampus, mammillary bodies, and anterior thalamic nuclei. Our results show
that the ventral hippocampal commissure (VHC) was visualized in all eight
individual DSI datasets, as well as in the DSI and HCP group datasets, but a
strictly defined VHC was only visualized in one individual dataset. Thalamic
fibers were observed to connect with both the posterior cingulate cortex (PCC)
and retrosplenial cortex (RSC). The RSC was mainly responsible for direct
hippocampal connections, while the PCC was not. This indicates that the RSC and
PCC represent separate functional hubs in humans, as also shown by previous
primate axonal tracing studies and functional magnetic resonance imaging
observations.
PMID- 28411160
TI - Life on the rocks: Multilocus phylogeography of rock hyrax (Procavia capensis)
from southern Africa.
AB - Understanding the role of geography and climatic cycles in determining patterns
of biodiversity is important in comparative and evolutionary biology and
conservation. We studied the phylogeographic pattern and historical demography of
a rock-dwelling small mammal species from southern Africa, the rock hyrax
Procavia capensis capensis. Using a multilocus coalescent approach, we assessed
the influence of strong habitat dependence and fluctuating regional climates on
genetic diversity. We sequenced a mitochondrial gene (cytochrome b) and two
nuclear introns (AP5, PRKC1) supplemented with microsatellite genotyping, in
order to assess evolutionary processes over multiple temporal scales. In
addition, distribution modelling was used to investigate the current and
predicted distribution of the species under different climatic scenarios.
Collectively, the data reveal a complex history of isolation followed by
secondary contact shaping the current intraspecific diversity. The cyt b
sequences confirmed the presence of two previously proposed geographically and
genetically distinct lineages distributed across the southern African Great
Escarpment and north-western mountain ranges. Molecular dating suggests Miocene
divergence of the lineages, yet there are no discernible extrinsic barriers to
gene flow. The nuclear markers reveal incomplete lineage sorting or ongoing
mixing of the two lineages. Although the microsatellite data lend some support to
the presence of two subpopulations, there is weak structuring within and between
lineages. These data indicate the presence of gene flow from the northern into
the southern parts of the southern African sub-region likely following the
secondary contact. The distribution modelling predictably reveal the species'
preference for rocky areas, with stable refugia through time in the northern
mountain ranges, the Great Escarpment, as well as restricted areas of the
Northern Cape Province and the Cape Fold Mountains of South Africa. Different
microclimatic variables appear to determine the distributional range of the
species. Despite strong habitat preference, the micro-habitat offered by rocky
crevices and unique life history traits likely promoted the adaptability of P.
capensis, resulting in the widespread distribution and persistence of the species
over a long evolutionary period. Spatio-temporal comparison of the evolutionary
histories of other co-distributed species across the rocky landscapes of southern
Africa will improve our understanding of the regional patterns of biodiversity
and local endemism.
PMID- 28411161
TI - A reassessment of the phylogeny and circumscription of Zaluzianskya
(Scrophulariaceae).
AB - The genus Zaluzianskya (Scrophulariaceae s.s.) encompasses a diversity of floral
and ecological traits. However, this diversity, as described by the current
taxonomic circumscription of Zaluzianskya, is an underestimate. We present
molecular data suggesting that this genus requires expansion via incorporation of
species from other genera and recognition of unnamed cryptic species. This study
advances prior molecular phylogenies of the southern African genus through the
addition of DNA regions and 51 populations that had not previously been sampled
in a published phylogeny. A total of 82 species of Zaluzianskya and related
genera are included, adding 48 to those previously sampled. Results are presented
from analyses of five DNA regions, including nuclear ITS and four rapidly
evolving chloroplast regions (trnL-trnF, rpl16, rps16, and trnS-trnfM). Our
primary finding is that the genus Phyllopodium is polyphyletic as currently
circumscribed, with some species placed within Zaluzianskya and others grouping
with Polycarena, indicating the need for further phylogenetic work on these
genera. Preliminary support for the incorporation of Reyemia into Zaluzianskya is
reinforced here by the first molecular analysis to include both species of
Reyemia and a strong sampling of species across Zaluzianskya and major clades of
tribe Limoselleae. The two disjunct, tropical African species of Zaluzianskya are
also confirmed as members of this genus. Finally, a broad sampling of 21
populations of Z. microsiphon establishes their phylogenetic division into two to
five separate lineages. Hybridization, coevolution, and cryptic speciation may
each play a role in the evolution of Z. microsiphon. Further resolution within a
clade comprising sections Nycterinia and Macrocalyx is needed to better
understand their relationships.
PMID- 28411162
TI - Insights into evolution in Andean Polystichum (Dryopteridaceae) from expanded
understanding of the cytosolic phosphoglucose isomerase gene.
AB - Cytosolic phosphoglucose isomerase (pgiC) is an enzyme essential to glycolysis
found universally in eukaryotes, but broad understanding of variation in the gene
coding for pgiC is lacking for ferns. We used a substantially expanded
representation of the gene for Andean species of the fern genus Polystichum to
characterize pgiC in ferns relative to angiosperms, insects, and an amoebozoan;
assess the impact of selection versus neutral evolutionary processes on pgiC; and
explore evolutionary relationships of selected Andean species. The dataset of
complete sequences comprised nine accessions representing seven species and one
hybrid from the Andes and Serra do Mar. The aligned sequences of the full data
set comprised 3376 base pairs (70% of the entire gene) including 17 exons and 15
introns from two central areas of the gene. The exons are highly conserved
relative to angiosperms and retain substantial homology to insect pgiC, but
intron length and structure are unique to the ferns. Average intron size is
similar to angiosperms; intron number and location in insects are unlike those of
the plants we considered. The introns included an array of indels and, in intron
7, an extensive microsatellite array with potential utility in analyzing
population-level histories. Bayesian and maximum-parsimony analysis of 129
variable nucleotides in the Andean polystichums revealed that 59 (1.7% of the
3376 total) were phylogenetically informative; most of these united sister
accessions. The phylogenetic trees for the Andean polystichums were incongruent
with previously published cpDNA trees for the same taxa, likely the result of
rapid evolutionary change in the introns and contrasting stability in the exons.
The exons code a total of seven amino-acid substitutions. Comparison of non
synonymous to synonymous substitutions did not suggest that the pgiC gene is
under selection in the Andes. Variation in pgiC including two additional
accessions represented by incomplete sequences provided new insights into
reticulate relationships among Andean taxa.
PMID- 28411163
TI - Development of a multi-epitope peptide vaccine inducing robust T cell responses
against brucellosis using immunoinformatics based approaches.
AB - Current investigations have demonstrated that a multi-epitope peptide vaccine
targeting multiple antigens could be considered as an ideal approach for
prevention and treatment of brucellosis. According to the latest findings, the
most effective immunogenic antigens of brucella to induce immune responses are
included Omp31, BP26, BLS, DnaK and L7-L12. Therefore, in the present study, an
in silico approach was used to design a novel multi-epitope vaccine to elicit a
desirable immune response against brucellosis. First, five novel T-cell epitopes
were selected from Omp31, BP26, BLS, DnaK and L7-L12 proteins using different
servers. In addition, helper epitopes selected from Tetanus toxin fragment C
(TTFrC) were applied to induce CD4+ helper T lymphocytes (HTLs) responses.
Selected epitopes were fused together by GPGPG linkers to facilitate the immune
processing and epitope presentation. Moreover, cholera toxin B (CTB) was linked
to N terminal of vaccine construct as an adjuvant by using EAAAK linker. A multi
epitope vaccine was designed based on predicted epitopes which was 377 amino acid
residues in length. Then, the physico-chemical properties, secondary and tertiary
structures, stability, intrinsic protein disorder, solubility and allergenicity
of this multi-epitope vaccine were assessed using immunoinformatics tools and
servers. Based on obtained results, a soluble, and non-allergic protein with
40.59kDa molecular weight was constructed. Expasy ProtParam classified this
chimeric protein as a stable protein and also 89.8% residues of constructed
vaccine were located in favored regions of the Ramachandran plot. Furthermore,
this multi-epitope peptide vaccine was able to strongly induce T cell and B-cell
mediated immune responses. In conclusion, immunoinformatics analysis indicated
that this multi-epitope peptide vaccine can be effectively expressed and
potentially be used for prophylactic or therapeutic usages against brucellosis.
PMID- 28411164
TI - High levels of local inter- and intra-host genetic variation of West Nile virus
and evidence of fine-scale evolutionary pressures.
AB - West Nile virus (WNV; Flaviviridae, Flavivirus) has been endemic in New York
State (NYS) since its 1999 introduction, yet prevalence in Culex mosquitoes
varies substantially over small spatial and temporal scales. It is unclear if
viral genetics plays a role in this variability, as genetic and phenotypic
characterization on local scales has generally been lacking. In addition,
intrahost diversity of circulating strains have not been fully characterized
despite the documented role of minority variants in viral fitness and virulence.
In an effort to characterize WNV variability within epidemiologically relevant
scales, we performed phylogenetic analyses on NYS isolates from 1999 to 2012. In
addition, we performed full-genome, deep-sequencing and genetic analyses on 15
WNV strains isolated in 2012 from Cx. pipiens in an endemic focus of Suffolk
County, NY. Our results indicate continued evolution and seasonal maintenance in
NYS, yet also widespread mixing and high levels of genetic diversity within
geographic foci and individual seasons. Well supported local clusters with shared
amino acid differences were identified and suggest local evolutionary pressures
and the potential for phenotypic variability. Intrahost diversity of focal
isolates was also high, with polymorphism at levels >1.0% identified in
approximately 10% of the WNV genome. Although most minority mutations were
unique, mutational hotspots shared among local isolates were identified,
particularly in C, NS1 and NS2A genes. The most polymorphic region, positions
3198-3388 of the NS1 gene, was comprised predominately of non-synonymous
mutations, suggesting a selective advantage for amino acid diversity in this
region.
PMID- 28411165
TI - Vitamin D and Sjogren syndrome.
AB - The immunomodulatory effects of vitamin D have been extensively studied in the
context of autoimmunity. Multiple studies have demonstrated a high prevalence of
vitamin D deficiency in autoimmune diseases. Recently, a possible protective role
of vitamin D in autoimmunity has been described; however, this function remains
controversial. Few studies have investigated the role of vitamin D in patients
with Sjogren syndrome (SS). In this review, we compiled the main features of SS
pathogenesis, the vitamin D immunomodulatory effects and the possible interaction
between both. Data suggests that vitamin D may play a role in the SS
pathogenesis. In addition, vitamin D low levels have been found in SS patients,
which are associated with extra-glandular manifestations, such as lymphoma or
neuropathy, suggesting a possible benefit effect of vitamin D in SS.
PMID- 28411166
TI - Antiphospholipid antibodies can identify lupus patients at risk of pulmonary
hypertension: A systematic review and meta-analysis.
AB - BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition that may
affect outcomes in patients with systemic lupus erythematosus (SLE). The role of
antiphospholipid antibodies (aPL) on the risk of PH is controversial. Therefore
our objective was to estimate the risk of PH (WHO groups 1-5) including
associated pulmonary arterial hypertension (APAH, WHO group 1 only) related to
aPL in patients with SLE. METHODS: Systematic review and meta-analysis were
performed: MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference
lists of eligible studies were searched through 2015. Studies were selected if
they included SLE patients with descriptions of the exposure to aPL and the
outcomes (PH including APAH). Two reviewers extracted study characteristics and
outcome data from published reports. Estimates were pooled using random effects
models and sensitivity analyses. PROSPERO registration number: CRD42015016872.
RESULTS: Of 984 identified abstracts, 31 primary studies (five cohorts, 13 case
control, 13 cross-sectional) met inclusion criteria, including 4480 SLE patients.
Prevalence of PH in aPL-positive vs. aPL-negative SLE patients was 12.3% vs.
7.3%, respectively. The overall pooled odds ratio (OR) for PH was 2.28 (95% CI,
1.65 to 3.15) (I2=39%). The risk of APAH was also significantly increased
(OR=2.62 [95% CI, 1.11-6.15]). The risk of PH was the highest for lupus
anticoagulant (OR=1.96 [95% CI, 1.31-2.92]) and IgG anticardiolipin antibodies
(OR=2.64 [95% CI, 1.30-5.36]) while other antibodies were not significantly
associated with PH. CONCLUSIONS: Among SLE patients, aPL can identify patients at
risk for PH and APAH. These findings warrant implementation of effective
screening and early treatment strategies.
PMID- 28411167
TI - Mast cells in rheumatoid arthritis: friends or foes?
AB - Mast cells are tissue-resident cells of the innate immunity, implicated in the
pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA).
They are present in synovia and their activation has been linked to the
potentiation of inflammation in the course of RA. However, recent investigations
questioned the role of mast cells in arthritis. In particular, animal models
generated conflicting results, so that many of their pro-inflammatory, i.e. pro
arthritogenic functions, even though supported by robust experimental evidence,
have been labelled as redundant. At the same time, a growing body of evidence
suggests that mast cells can act as tunable immunomodulatory cells. These
characteristics, not yet fully understood in the context of RA, could partially
explain the inconsistent results obtained with experimental models, which do not
account for the pro- and anti-inflammatory functions exerted in more chronic
heterogeneous conditions such as RA. Here we present an overview of the current
knowledge on mast cell involvement in RA, including the intriguing hypothesis of
mast cells acting as subtle immunomodulatory cells and the emerging concept of
synovial mast cells as potential biomarkers for patient stratification.
PMID- 28411168
TI - Dysregulated homeostasis of target tissues or autoantigens - A novel principle in
autoimmunity.
AB - Monogenic autoimmune disorders provide a powerful tool for our understanding of
the principles of autoimmunity due to the obvious impact of a single gene on the
disease. So far, approximately 100 single gene defects causing murine monogenic
autoimmune disorders have been reported and the functional characterization of
these genes will provide significant progress in understanding the nature of
autoimmunity. According to their function, genes leading to monogenic autoimmune
disorders can be categorized into two groups. An expectable first group contains
genes involved in the homeostasis of the immune system, including homeostasis of
immune organs and immune cells. Intriguingly, the second group consists of genes
functionally involved in the homeostasis of target tissues or autoantigens.
According to our novel hypothesis, we propose that autoimmunity represents a
consequence of a dysregulated homeostasis of the immune system and/or its targets
including autoantigens and target tissues. In this review we refer to both
aspects of homeostasis in autoimmunity with a highlight on the role of the
homeostasis of target tissues and autoantigens.
PMID- 28411169
TI - The impact of immunogenicity of TNFalpha inhibitors in autoimmune inflammatory
disease. A systematic review and meta-analysis.
AB - BACKGROUND: Monoclonal antibodies drugs directed against TNFalpha, TNFalpha
inhibitors, are immunogenic, and consequent anti-drug antibodies (ADA) formation
may decrease the functional drug concentration, resulting in a loss of response.
We evaluated the impact of ADA on TNFalpha therapeutic response. METHODS: We
considered studies enrolling adult patients affected by autoimmune inflammatory
disease in therapy with TNFalpha inhibitors. We collected data about study and
population characteristics, treatment dosage, determination of ADA and adverse
events (AE). We combined data in meta-analysis, calculating risk ratios (RR) for
each study. p-Values<0.05 were considered as statistically significant.
Methodological quality was evaluated. Analyses were performed with the STATA 11
and RevMan 5.3 softwares. RESULTS: We included 34 studies enrolling 4273
patients. Of these, 794 (18.6%) developed ADA. Our analysis showed a significant
reduction of response (RR 0.43, 95%CI 0.3-0.63) in patients with ADA respect to
patients without, especially in patients treated with Infliximab (RR 0.37) or
Adalimumab (RR 0.40). Furthermore, the administration of TNFalpha inhibitors
produced a reaction at the infusion site in 17%, infection in 30% and serious AE
in 5% of patients. CONCLUSION: Detectable ADA significantly reduced TNFalpha
inhibitors response. Drug administration can also cause injection site reaction
and infections. Early detection of serum ADA levels may improve patients'
management. Currently, there are many indications about the use of immunogenicity
tests to guide the therapy, but information regarding how to implement it in
clinical practice is needed.
PMID- 28411170
TI - The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism
in health and disease.
AB - Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant
phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and
co-workers performed groundbreaking research that established the general outline
of many of the pathways of phospholipid biosynthesis. In recent years, the
importance of phospholipid metabolism in regulating lipid, lipoprotein and whole
body energy metabolism has been demonstrated in numerous dietary studies and
knockout animal models. The purpose of this review is to highlight the
unappreciated impact of phospholipid metabolism on health and disease. Abnormally
high, and abnormally low, cellular PC/PE molar ratios in various tissues can
influence energy metabolism and have been linked to disease progression. For
example, inhibition of hepatic PC synthesis impairs very low density lipoprotein
secretion and changes in hepatic phospholipid composition have been linked to
fatty liver disease and impaired liver regeneration after surgery. The relative
abundance of PC and PE regulates the size and dynamics of lipid droplets. In
mitochondria, changes in the PC/PE molar ratio affect energy production. We
highlight data showing that changes in the PC and/or PE content of various
tissues are implicated in metabolic disorders such as atherosclerosis, insulin
resistance and obesity. This article is part of a Special Issue entitled:
Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.
PMID- 28411171
TI - G protein-membrane interactions II: Effect of G protein-linked lipids on membrane
structure and G protein-membrane interactions.
AB - G proteins often bear myristoyl, palmitoyl and isoprenyl moieties, which favor
their association with the membrane and their accumulation in G Protein Coupled
Receptor-rich microdomains. These lipids influence the biophysical properties of
membranes and thereby modulate G protein binding to bilayers. In this context, we
showed here that geranylgeraniol, but neither myristate nor palmitate, increased
the inverted hexagonal (HII) phase propensity of phosphatidylethanolamine
containing membranes. While myristate and palmitate preferentially associated
with phosphatidylcholine membranes, geranylgeraniol favored nonlamellar-prone
membranes. In addition, Galphai1 monomers had a higher affinity for lamellar
phases, while Gbetagamma and Galphabetagamma showed a marked preference for
nonlamellar prone membranes. Moreover, geranylgeraniol enhanced the binding of G
protein dimers and trimers to phosphatidylethanolamine-containing membranes, yet
it decreased that of monomers. By contrast, both myristate and palmitate
increased the Galphai1 preference for lamellar membranes. Palmitoylation
reinforced the binding of the monomer to PC membranes and myristoylation
decreased its binding to PE-enriched bilayer. Finally, binding of dimers and
trimers to lamellar-prone membranes was decreased by palmitate and myristate, but
it was increased in nonlamellar-prone bilayers. These results demonstrate that
co/post-translational G protein lipid modifications regulate the membrane lipid
structure and that they influence the physico-chemical properties of membranes,
which in part explains why G protein subunits sort to different plasma membrane
domains. This article is part of a Special Issue entitled: Membrane Lipid
Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.
PMID- 28411172
TI - Computational study on human sphingomyelin synthase 1 (hSMS1).
AB - Human sphingomyelin synthase 1 (hSMS1) is the last enzyme for sphingomyelin (SM)
biosynthesis. It has been discovered that in different human tumor tissues the SM
levels are lower compared to normal tissues and the activation of hSMS1, to
restore the normal levels of SM, inhibits cell cycle proliferation of cancer
cells. Since the importance of SM and other lipid metabolism genes in the
malignant transformation, we decided to explore the hSMS1 mechanism of action.
Enzymes capable to regulate the formation of lipids are therefore of paramount
importance. Here we present a computational study on sphingomyelin synthases
hSMS1. The full structure of the enzyme was obtained by means of homology and ab
initio techniques. Further molecular dynamics and docking studies permitted to
identify putative binding sites and to identify the key residues for binding.
This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs
Targeting Biomembranes edited by Pablo V. Escriba.
PMID- 28411174
TI - Evaluation of Hematopoietic Stem Cell Mobilization Rates with Early Plerixafor
Administration for Adult Stem Cell Transplantation.
AB - The addition of plerixafor to high-dose colony-stimulating growth factor has been
shown to improve stem cell mobilization rates in autologous transplant patients
with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change
in administration time of plerixafor to determine if cell mobilization rates are
similar between the US Food and Drug Administration-approved administration time
of 11 hours before apheresis and an earlier administration time of 16 hours
before apheresis. Medical records of patients age >= 18 years undergoing
autologous stem cell transplantation requiring the use of plerixafor after at
least 4 days of granulocyte colony-stimulating factor therapy to complete stem
cell mobilization from January 1, 2010 through September 30, 2014 were
retrospectively reviewed. The primary outcome was CD34+ cell mobilization success
rates when plerixafor was administered 11 +/- 2 hours (standard administration
group) compared with 16 +/- 2 hours before cell apheresis (early administration
group), as defined as collection of >=2 * 106 CD34+ cells/kg. Secondary outcomes
included the number of plerixafor therapy days required to collect a total of >=2
* 106 CD34+ cells/kg, the number of apheresis cycles required to achieve >=2 *
106 CD34+ cells/kg, the median CD34+ cells/kg collected in each apheresis
session, and the rates of reported adverse events that occurred in the standard
administration time group compared with the early administration time group. Of
the 197 patients included, 114 patients received plerixafor 11 +/- 2 hours before
apheresis and 83 patients received plerixafor 16 hours +/- 2 hours before
apheresis. Ninety-four percent of patients in the early administration group
achieved successful stem cell mobilization compared with 81.6% in the standard
administration group (P = .0111). The median number of plerixafor days to reach
the collection goal of >=2 * 106 CD34+ cells/kg was 1 day for each group (P =
.323), and the median number of apheresis days to reach the collection goal was 2
days for the standard administration group compared with 1 day for the early
administration group (P = .0156). Most adverse events were similar between the 2
groups except for fever, which occurred in 4.8% of the patients in the early
administration group and none of the patients in the standard administration
group. This study demonstrates plerixafor effectively mobilizes peripheral blood
stem cells when given at an early administration time of 16 hours before
apheresis compared with standard administration of 11 hours before apheresis.
However, further prospective studies could strengthen these results.
PMID- 28411173
TI - Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond.
AB - The regulation of glycerolipid biosynthesis is critical for homeostasis of
cellular lipid stores and membranes. Here we review the role of lipin
phosphatidic acid phosphatase enzymes in glycerolipid synthesis. Lipin proteins
are unique among glycerolipid biosynthetic enzymes in their ability to transit
among cellular membranes, rather than remain membrane tethered. We focus on the
mechanisms that underlie lipin protein interactions with membranes and the
versatile roles of lipins in several organelles, including the endoplasmic
reticulum, mitochondria, endolysosomes, lipid droplets, and nucleus. We also
review the corresponding physiological roles of lipins, which have been uncovered
by the study of genetic lipin deficiencies. We propose that the growing body of
knowledge concerning the biochemical and cellular activities of lipin proteins
will be valuable for understanding the physiological functions of lipin proteins
in health and disease. This article is part of a Special Issue entitled: Membrane
Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.
PMID- 28411176
TI - Hematopoietic Stem Cell Transplant for a New Primary Immunodeficiency Disorder: A
Voyage Where No Transplant Physician Has Gone Before.
PMID- 28411175
TI - Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic
Hematopoietic Cell Transplant: A Study from the Center for International Blood
and Marrow Transplant Research (CIBMTR).
AB - Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent
solid tumors, including central nervous system (CNS) tumors. The risk of CNS
tumors after HCT in pediatric HCT recipients is not known. We evaluated the
incidence and risk factors for CNS tumors in pediatric recipients of allogeneic
HCT reported to the Center for International Blood and Marrow Transplant Research
between 1976 and 2008. A case control design was used. There were no CNS tumors
in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors
(n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic
malignancies. In comparison with the general population, pediatric HCT recipients
with hematologic malignancies had a 33 times higher than expected rate of CNS
tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative
incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to
1.87) at 20 years after HCT. Significant risk factors in the entire cohort were
having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for
both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid
leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an
unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR,
7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P =
.0234) to be significant risk factors. Chronic graft-versus-host disease was
associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for
nonmalignant diseases did not show an increased incidence of CNS tumors, whereas
survivors of hematologic malignancies have a markedly increased incidence of CNS
tumors that warrants lifelong surveillance.
PMID- 28411177
TI - Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of
papillary thyroid carcinoma with a solid component.
AB - Solid variant of papillary thyroid carcinoma (PTC) is characterized by a solid
component (SC) retaining classical cytological features of PTC. Despite some
controversies, PTC with SC (PTCSC) cases have poor prognosis compared with well
differentiated PTC. We investigated if cancer stem cells (CSCs) may have a role
in pathogenesis of PTCSC. PTCSC tumors (n=27) were histologically represented by
a mixture of papillary component (PC) and varying degrees of SC involving 10% to
85% of the tumor. Immunohistochemical expression of CSC markers ABCG2 and MRP1,
and HBME1 and CK19 was compared between SC and PC within each tumor in
association with clinicopathological parameters. ABCG2 and MRP1 were highly
expressed in SC, whereas their expression was limited or absent in PC (P=.04 and
.002, respectively). In contrast, expression of HBME1 and CK19 appeared higher in
PC than in SC (P=.08 and .02, respectively). Higher expression of ABCG2 was
associated with higher incidence of large-sized SC (P=.01). Higher expression of
MRP1 was associated with higher incidence of lymphovascular invasion (P=.049).
Higher expression of ABCG2 and MRP1, and lower expression of CK19 in SC were
associated with higher tumor recurrence rate (P=.02, .01, and .02, respectively),
and shorter disease-free survival (P<.001 for all the variables). Our findings
indicate that the tumor cells harboring CSC-like characteristics in SC could
contribute to the pathogenesis of PTCSC and might account for the poor disease
prognosis.
PMID- 28411178
TI - MicroRNA expression profiling of Xp11 renal cell carcinoma.
AB - Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a
distinctive molecular subtype characterized by chromosomal translocations
involving the Xp11.2 locus, resulting in gene fusions between the TFE3
transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ).
RCCs with Xp11 translocations comprise up to 1% to 4% of adult cases, frequently
displaying papillary architecture with epithelioid clear cells. To better
understand the biology of this molecularly distinct tumor subtype, we analyze the
microRNA (miRNA) expression profiles of Xp11 RCC compared with normal renal
parenchyma using microarray and quantitative reverse-transcription polymerase
chain reaction. We further compare Xp11 RCC with other RCC histologic subtypes
using publically available data sets, identifying common and distinctive miRNA
signatures along with the associated signaling pathways and biological processes.
Overall, Xp11 RCC more closely resembles clear cell rather than papillary RCC.
Furthermore, among the most differentially expressed miRNAs specific for Xp11
RCC, we identify miR-148a-3p, miR-221-3p, miR-185-5p, miR-196b-5p, and miR-642a
5p to be up-regulated, whereas miR-133b and miR-658 were down-regulated. Finally,
Xp11 RCC is most strongly associated with miRNA expression profiles modulating
DNA damage responses, cell cycle progression and apoptosis, and the Hedgehog
signaling pathway. In summary, we describe here for the first time the miRNA
expression profiles of a molecularly distinct type of renal cancer associated
with Xp11.2 translocations involving the TFE3 gene. Our results might help
understanding the molecular underpinning of Xp11 RCC, assisting in developing
targeted treatments for this disease.
PMID- 28411179
TI - Clusterin expression in medullary thyroid carcinoma is inversely correlated with
the presence of lymph node metastases.
AB - Clusterin (CLU) is a sulfated glycoprotein implicated in many physiological and
pathological processes, including tumorigenesis. Several studies have reported
the overexpression of CLU in human neoplasm, examined by immunohistochemistry.
However, there are no extensive data on its role in the thyroid. Here we
investigate CLU expression in thyroid tumors, and the potential correlation
between this expression and clinicopathological parameters. Immunohistochemistry
with anti-CLU was performed on paraffin sections from 39 thyroid tumors. Only
medullary thyroid carcinomas (MTCs) were positive (n = 5). To confirm these
results, 130 further cases (including 4 C-cell hyperplasia), their matched lymph
node metastases (46 cases), and lymph node recurrences (10 cases) were analyzed.
All MTCs were subdivided according to World Health Organization classification.
Cytoplasmic positivity was scored qualitatively (weak, moderate, strong) and
quantitatively on a 5-tier scale from 0, 1+ (<10% of cells positive) to 5+
(>75%). Statistical analysis was performed. CLU was expressed in normal C cells,
C-cell hyperplasia, all MTCs, their lymph node metastases, and recurrences. There
was a strong association between CLU score and the cellular type (P < .004). CLU
score was inversely correlated with the presence of lymph node metastases (P <
.0001). There were no differences between primary and metastatic or recurrent
tumors. CLU expression is related to the cellular type and inversely correlated
with the presence of lymph node metastases, which could represent a new positive
prognostic factor.
PMID- 28411180
TI - Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression
of PTEN and poor prognosis in patients with hepatocellular carcinoma.
AB - Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in
several cancers. A previous study has demonstrated that SALL4 interacts with the
nucleosome remodeling deacetylase complex, which contains histone deacetylase 1
(HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the
expression status of SALL4, HDAC1, and HDAC2 and their relationship with
phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by
immunohistochemical analysis of the posthepatectomy specimens of 135 patients
with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen
samples were subjected to quantitative reverse-transcription polymerase chain
reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%)
of 135 patients were positive for SALL4, and this group had a higher prevalence
of hepatitis B antigen, a higher value of alpha-fetoprotein (AFP) and protein
induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5
year survival rate was significantly lower in the SALL4-positive group. High
HDAC1 expression (51%) was correlated with a poor histologic differentiation and
a poor prognosis. High HDAC2 expression (46%) was associated with a higher
prevalence of hepatitis B antigen positivity, a poor histologic differentiation
and higher prevalence of vascular invasion, and a lower 5-year survival rate.
Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression
of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4
with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus
suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential
target for molecular therapy.
PMID- 28411181
TI - Monoclonal antibodies to the reactive centre loop (RCL) of human corticosteroid
binding globulin (CBG) can protect against proteolytic cleavage.
AB - Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation
and is a non-functional member of the family of serine protease inhibitors
(serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL
can be cleaved by human neutrophil elastase, released from activated neutrophils,
and can also be cleaved at nearby site(s) by elastase released by Pseudomonas
aeruginosa, and at two further sites, also within the RCL, by bovine
chymotrypsin. Cleavage of the RCL results in a conformational change accompanied
by a marked decrease in affinity for cortisol and hence its release at the site
of proteolysis. These cleavages are irreversible and the similar half-lives of
cleaved and intact CBG could mean that there may be some advantage in slowing the
rate of CBG cleavage in acute inflammation thereby increasing the proportion of
intact CBG in circulation. Here we show, for the first time, that pre-incubation
of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects
against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation
with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the
RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin
cleavage of the RCL. These findings may provide a basis and rationale for the
concept of the use of RCL antibodies as therapeutic agents to effectively
increase the proportion of intact CBG in circulation which may be of benefit in
acute inflammation.
PMID- 28411182
TI - PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in
vitro and in vivo.
AB - Small interfering RNAs (siRNAs) present a strong therapeutic potential because of
their ability to inhibit the expression of any desired protein. Recently, we
developed the retro-inverso amphipathic RICK peptide as novel non-covalent siRNA
carrier. This peptide is able to form nanoparticles (NPs) by self-assembling with
the siRNA resulting in the fully siRNA protection based on its protease resistant
peptide sequence. With regard to an in vivo application, we investigated here the
influence of the polyethylene glycol (PEG) grafting to RICK NPs on their in vitro
and in vivo siRNA delivery properties. A detailed structural study shows that
PEGylation did not alter the NP formation (only decrease in zeta potential)
regardless of the used PEGylation rates. Compared to the native RICK:siRNA NPs,
low PEGylation rates (<=20%) of the NPs did not influence their cellular
internalization capacity as well as their knock-down specificity (over-expressed
or endogenous system) in vitro. Because the behavior of PEGylated NPs could
differ in their in vivo application, we analyzed the repartition of fluorescent
labeled NPs injected at the one-cell stage in zebrafish embryos as well as their
pharmacokinetic (PK) profile after administration to mice. After an intra-cardiac
injection of the PEGylated NPs, we could clearly determine that 20% PEG-RICK NPs
reduce significantly liver and kidney accumulation. NPs with 20% PEGylation
constitutes a modular, easy-to-handle drug delivery system which could be adapted
to other types of functional moieties to develop safe and biocompatible delivery
systems for the clinical application of RNAi-based cancer therapeutics.
PMID- 28411183
TI - Membrane permeation of arginine-rich cell-penetrating peptides independent of
transmembrane potential as a function of lipid composition and membrane fluidity.
AB - Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer
cellular entry of (bio-) macromolecules. Internalization efficiency and uptake
mechanism depend, next to the type of CPP and cargo, also on cell type. Direct
penetration of the plasma membrane is the preferred route of entry as this
circumvents endolysosomal sequestration. However, the molecular parameters
underlying this import mechanism are still poorly defined. Here, we make use of
the frequently used HeLa and HEK cell lines to address the role of lipid
composition and membrane potential. In HeLa cells, at low concentrations, the CPP
nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration
occurs only at high peptide concentrations through a mechanism involving
activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK
cells, by comparison, R9 enters the cytoplasm through direct membrane permeation
already at low concentrations. This direct permeation is strongly reduced at room
temperature and upon cholesterol depletion, indicating a complex dependence on
membrane fluidity and microdomain organisation. Lipidomic analyses show that in
comparison to HeLa cells HEK cells have an endogenously low sphingomyelin
content. Interestingly, direct permeation in HEK cells and also in HeLa cells
treated with exogenous sphingomyelinase is independent of membrane potential.
Membrane potential is only required for induction of sphingomyelinase-dependent
uptake which is then associated with a strong hyperpolarization of membrane
potential as shown by whole-cell patch clamp recordings. Next to providing new
insights into the interplay of membrane composition and direct permeation, these
results also refute the long-standing paradigm that transmembrane potential is a
driving force for CPP uptake.
PMID- 28411184
TI - CMI theme issues: invitation to submit papers.
PMID- 28411185
TI - Detection of pyrazinamide resistance of Mycobacterium tuberculosis using
nicotinamide as a surrogate.
AB - OBJECTIVES: Despite the importance of pyrazinamide (PZA) in tuberculosis
treatment, PZA susceptibility testing is not routinely performed because of its
acid pH requirement. We evaluated the Microplate Alamar Blue assay (MABA) to
detect resistance to PZA using nicotinamide (NIC) as a surrogate in neutral pH
and identify the appropriate cutoff point for the assay. METHODS: The NIC minimal
inhibition concentrations (MICs) for 125 Mycobacterium tuberculosis clinical
isolates were tested by MABA at nine different concentrations (8-2000 MUg/mL).
The PZA susceptibility testing by the BACTEC MGIT 960 system was used as a
reference method. The pncA gene and its promoter region were sequenced for all
the recruited strains. RESULTS: A total of 64 of 125 clinical isolates were
identified as resistant by MGIT 960. Using a minimum inhibitory concentration
(MIC) of >500 MUg/mL as the cutoff concentration to define resistance presented
the best fit of the MABA assay with the MGIT 960 outcomes. MABA demonstrated
sensitivity of 100% (95% confidence interval, 92.6-100), specificity of 95.2%
(95% confidence interval, 86.0-98.8) and an accuracy of 97.6% compared to the
MGIT 960 method. Nine PZA susceptible strains defined by MGIT 960 also had pncA
mutations; however, three of them were defined as PZA resistant by NIC MABA with
MIC >=2000 MUg/mL. CONCLUSIONS: The NIC substitution method for PZA
susceptibility test is reliable, cheap, rapid and easy, which makes it promising
for use in clinical laboratories.
PMID- 28411186
TI - Direct Antimicrobial Activity of IFN-beta.
AB - Type I IFNs are a cytokine family essential for antiviral defense. More recently,
type I IFNs were shown to be important during bacterial infections. In this
article, we show that, in addition to known cytokine functions, IFN-beta is
antimicrobial. Parts of the IFN-beta molecular surface (especially helix 4) are
cationic and amphipathic, both classic characteristics of antimicrobial peptides,
and we observed that IFN-beta can directly kill Staphylococcus aureus Further, a
mutant S. aureus that is more sensitive to antimicrobial peptides was killed more
efficiently by IFN-beta than was the wild-type S. aureus, and immunoblotting
showed that IFN-beta interacts with the bacterial cell surface. To determine
whether specific parts of IFN-beta are antimicrobial, we synthesized IFN-beta
helix 4 and found that it is sufficient to permeate model prokaryotic membranes
using synchrotron x-ray diffraction and that it is sufficient to kill S. aureus
These results suggest that, in addition to its well-known signaling activity, IFN
beta may be directly antimicrobial and be part of a growing family of cytokines
and chemokines, called kinocidins, that also have antimicrobial properties.
PMID- 28411187
TI - The Nuclear Receptor Nr4a1 Acts as a Microglia Rheostat and Serves as a
Therapeutic Target in Autoimmune-Driven Central Nervous System Inflammation.
AB - Microglia cells fulfill key homeostatic functions and essentially contribute to
host defense within the CNS. Altered activation of microglia, in turn, has been
implicated in neuroinflammatory and neurodegenerative diseases. In this study, we
identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the
activation threshold and polarization of microglia. In steady-state microglia,
ubiquitous neuronal-derived stress signals such as ATP induced expression of this
NR, which contributed to the maintenance of a resting and noninflammatory
microglia phenotype. Global and microglia-specific deletion of Nr4a1 triggered
the spontaneous and overwhelming activation of microglia and resulted in
increased cytokine and NO production as well as in an accelerated and exacerbated
form of experimental autoimmune encephalomyelitis. Ligand-induced activation of
Nr4a1 accordingly ameliorated the course of this disease. Our current data thus
identify Nr4a1 as regulator of microglia activation and potentially new target
for the treatment of inflammatory CNS diseases such as multiple sclerosis.
PMID- 28411188
TI - Raf Kinase Inhibitor Protein Preferentially Promotes TLR3-Triggered Signaling and
Inflammation.
AB - Raf kinase inhibitor protein (RKIP) protects against host immunological responses
in nematodes and Drosophila Whether RKIP functions in innate immune responses in
mammals remains unknown. In this article, we report that RKIP preferentially
regulates the TLR3-mediated immune response in macrophages. RKIP deficiency or
silencing significantly decreases polyinosinic:polycytidylic acid [Poly(I:C)]
induced IFN-beta, IL-6, and TNF-alpha production without affecting the
counterpart induced by LPS or CpG. Compared with their wild-type counterparts,
RKIP-deficient mice produce less IFN-beta, IL-6, and TNF-alpha in serum and
display decreased lethality upon peritoneal Poly(I:C) plus d-galactosamine
injection. Mechanistically, RKIP interacts with TBK1 and promotes the Poly(I:C)
induced TANK-binding kinase 1/IRF3 activation. Simultaneously, RKIP enhances the
Poly(I:C)-induced interaction between TGF-beta-activated kinase 1 and MAPK kinase
3 (MKK3), thus promoting MKK3/6 and p38 activation. We further demonstrated that
Poly(I:C) treatment, but not LPS treatment, induces RKIP phosphorylation at S109.
This action is required for RKIP to promote TANK-binding kinase 1 activation, as
well as the interaction between TGF-beta-activated kinase 1 and MKK3, which lead
to activation of the downstream IRF3 and p38, respectively. Therefore, RKIP acts
as a positive-feedback regulator of the TLR3-induced inflammatory response and
may be a potential therapeutic target for inflammatory disease.
PMID- 28411190
TI - The evolutionary origins of antagonistic neurotrophin signaling.
AB - A competitive balance between constructive and destructive developmental cues
governs both the form and function of the vertebrate nervous system. In this
issue, Foldi et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607098)
explore the evolutionary origins of these cues and report that in Drosophila
melanogaster pro- and mature neurotrophins are capable of inducing death and
survival pathways, respectively, by binding Toll receptor family members, which
then recruit distinct sets of effector proteins.
PMID- 28411189
TI - Centrioles initiate cilia assembly but are dispensable for maturation and
maintenance in C. elegans.
AB - Cilia are cellular projections that assemble on centriole-derived basal bodies.
While cilia assembly is absolutely dependent on centrioles, it is not known to
what extent they contribute to downstream events. The nematode C. elegans
provides a unique opportunity to address this question, as centrioles do not
persist at the base of mature cilia. Using fluorescence microscopy and electron
tomography, we find that centrioles degenerate early during ciliogenesis. The
transition zone and axoneme are not completely formed at this time, indicating
that cilia maturation does not depend on intact centrioles. The hydrolethalus
syndrome protein HYLS-1 is the only centriolar protein known to remain at the
base of mature cilia and is required for intraflagellar transport trafficking.
Surprisingly, targeted degradation of HYLS-1 after initiation of ciliogenesis
does not affect ciliary structures. Taken together, our results indicate that
while centrioles are essential to initiate cilia formation, they are dispensable
for cilia maturation and maintenance.
PMID- 28411191
TI - Delivering Clinical Grade Sequencing and Genetic Test Interpretation for
Cardiovascular Medicine.
PMID- 28411192
TI - Socioeconomic Status Interacts with the Genetic Effect of a Chromosome 9p21.3
Common Variant to Influence Coronary Artery Calcification and Incident Coronary
Events in the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary
Calcium, and Lifestyle).
AB - BACKGROUND: Genetic variants of a locus within the chromosome 9p21.3 region are
consistently associated with coronary artery disease and coronary artery
calcification (CAC). The aim of this study was to examine whether a 9p21.3 common
variant interacts with socioeconomic status (SES) to influence CAC and incident
coronary events in a population-based cohort. METHODS AND RESULTS: 9p21.3 single
nucleotide polymorphism rs2891168 was genotyped in 4116 participants of the Heinz
Nixdorf Recall study. SES indicators (education and income) and CAC were assessed
at baseline. Incident coronary events were ascertained over a median follow-up of
9.3 years. Multiple regression models were fitted to estimate genetic effects on
loge(CAC+1) and incident coronary events. Genetic effects were highest in the
lower income tertile with a 53.1% (95% confidence interval, 30.6%-79.6%; P=1.8*10
-7) increase in CAC and a hazard ratio of 1.44 (95% confidence interval, 1.01
2.07; P=0.049) for incident coronary events per additional risk allele. After
including genotype*SES interaction terms in the regression models,
genotype*income interactions were observed for CAC (exp[betag*income]=0.85 [95%
confidence interval, 0.74-0.98; Pg*income=0.02] per 1000?/mo increase and
additional risk allele) and for incident coronary events (hazard
ratiog*income=0.69 [95% confidence interval, 0.48-0.98; Pg*income=0.04] per
1000?/mo increase and additional risk allele). No interaction was observed using
education as SES indicator. CONCLUSIONS: A 9p21.3 common variant seems to
interact with SES to influence CAC and incident coronary events in a population
based cohort. This supports the hypothesis that better material, psychosocial,
and lifestyle conditions enable higher SES groups to reduce the expression of
their genetic susceptibility to coronary artery disease.
PMID- 28411193
TI - Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in
Patients with Melanoma and NSCLC.
AB - We explored the association between liver metastases, tumor CD8+ T-cell count,
and response in patients with melanoma or lung cancer treated with the anti-PD-1
antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I
Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote
002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from
Keynote 001. Liver metastasis was associated with reduced response and shortened
progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS,
5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median
PFS, 20.1 months) P <= 0.0001, and confirmed in the validation cohort (P =
0.0006). The presence of liver metastasis significantly increased the likelihood
of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n =
62), liver metastasis was associated with reduced CD8+ T-cell density at the
invasive tumor margin (liver metastasis+ group, n = 547 +/- 164.8; liver
metastasis- group, n = 1,441 +/- 250.7; P < 0.016). A reduced response rate and
shortened PFS was also observed in NSCLC patients with liver metastasis [median
PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those
without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P =
0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been
treated with pembrolizumab were associated with reduced responses and PFS, and
liver metastases were associated with reduced marginal CD8+ T-cell infiltration,
providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417
24. (c)2017 AACR.
PMID- 28411196
TI - Correction: SENP1 deSUMOylates and Regulates Pin1 Protein Activity and Cellular
Function.
PMID- 28411197
TI - Correction: Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia.
PMID- 28411194
TI - Systematic characterization of A-to-I RNA editing hotspots in microRNAs across
human cancers.
AB - RNA editing, a widespread post-transcriptional mechanism, has emerged as a new
player in cancer biology. Recent studies have reported key roles for individual
miRNA editing events, but a comprehensive picture of miRNA editing in human
cancers remains largely unexplored. Here, we systematically characterized the
miRNA editing profiles of 8595 samples across 20 cancer types from miRNA
sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine
(A-to-I) RNA editing hotspots. We independently validated 15 of them by
perturbation experiments in several cancer cell lines. These miRNA editing events
show extensive correlations with key clinical variables (e.g., tumor subtype,
disease stage, and patient survival time) and other molecular drivers. Focusing
on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we
found that the miR-200b editing level correlates with patient prognosis opposite
to the pattern observed for the wild-type miR-200b expression. We further
experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b
can promote cell invasion and migration through its impaired ability to inhibit
ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including
LIFR, a well-characterized metastasis suppressor. Our study highlights the
importance of miRNA editing in gene regulation and suggests its potential as a
biomarker for cancer prognosis and therapy.
PMID- 28411198
TI - Correction: EGFL6 Regulates the Asymmetric Division, Maintenance, and Metastasis
of ALDH+ Ovarian Cancer Cells.
PMID- 28411199
TI - Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in
mice.
AB - Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier
protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)]
gene products facilitate hepatic uptake and metabolism of lipotoxic dietary
phytol. However, interpretation of physiological function in mice singly gene
ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of
FABP1. The work presented herein provides several novel insights: i) An 8-anilino
1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L
FABP bound phytol, but both had high affinity for its metabolite, phytanic acid;
ii) GC-MS studies with phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple
KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of phytol
metabolites in vivo in females and less so in males. Concomitantly, dietary
phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both
male and female WT and TKO mice. Moreover, in both WT and TKO female mice,
dietary phytol increased hepatic ratios of saturated/unsaturated and
polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability
index. However, in male mice, dietary phytol selectively increased the
saturated/unsaturated ratio only in TKO mice, while decreasing the
peroxidizability index in both WT and TKO mice. These findings suggested that: 1)
SCP-2 and FABP1 both facilitated phytol metabolism after its conversion to
phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic phytol
metabolism than FABP1.
PMID- 28411201
TI - CORRIGENDUM.
PMID- 28411200
TI - Isolation and characterization of a thermostable F420:NADPH oxidoreductase from
Thermobifida fusca.
AB - F420H2-dependent enzymes reduce a wide range of substrates that are otherwise
recalcitrant to enzyme-catalyzed reduction, and their potential for applications
in biocatalysis has attracted increasing attention. Thermobifida fusca is a
moderately thermophilic bacterium and holds high biocatalytic potential as a
source for several highly thermostable enzymes. We report here on the isolation
and characterization of a thermostable F420: NADPH oxidoreductase (Tfu-FNO) from
T. fusca, the first F420-dependent enzyme described from this bacterium. Tfu-FNO
was heterologously expressed in Escherichia coli, yielding up to 200 mg of
recombinant enzyme per liter of culture. We found that Tfu-FNO is highly
thermostable, reaching its highest activity at 65 degrees C and that Tfu-FNO is
likely to act in vivo as an F420 reductase at the expense of NADPH, similar to
its counterpart in Streptomyces griseus We obtained the crystal structure of FNO
in complex with NADP+ at 1.8 A resolution, providing the first bacterial FNO
structure. The overall architecture and NADP+-binding site of Tfu-FNO were highly
similar to those of the Archaeoglobus fulgidus FNO (Af-FNO). The active site is
located in a hydrophobic pocket between an N-terminal dinucleotide binding domain
and a smaller C-terminal domain. Residues interacting with the 2'-phosphate of
NADP+ were probed by targeted mutagenesis, indicating that Thr-28, Ser-50, Arg
51, and Arg-55 are important for discriminating between NADP+ and NAD+
Interestingly, a T28A mutant increased the kinetic efficiency >3-fold as compared
with the wild-type enzyme when NADH is the substrate. The biochemical and
structural data presented here provide crucial insights into the molecular
recognition of the two cofactors, F420 and NAD(P)H by FNO.
PMID- 28411202
TI - Characterization of the mammalian DEAD-box protein DDX5 reveals functional
conservation with S. cerevisiae ortholog Dbp2 in transcriptional control and
glucose metabolism.
AB - DEAD-box proteins are a class of nonprocessive RNA helicases that dynamically
modulate the structure of RNA and ribonucleoprotein complexes (RNPs). However,
the precise roles of individual members are not well understood. Work from our
laboratory revealed that the DEAD-box protein Dbp2 in Saccharomyces cerevisiae is
an active RNA helicase in vitro that functions in transcription by promoting mRNP
assembly, repressing cryptic transcription initiation, and regulating long
noncoding RNA activity. Interestingly, Dbp2 is also linked to glucose sensing and
hexose transporter gene expression. DDX5 is the mammalian ortholog of Dbp2 that
has been implicated in cancer and metabolic syndrome, suggesting that the role of
Dbp2 and DDX5 in glucose metabolic regulation is conserved. Herein, we present a
refined biochemical and biological comparison of yeast Dbp2 and human DDX5
enzymes. We find that human DDX5 possesses a 10-fold higher unwinding activity
than Dbp2, which is partially due to the presence of a mammalian/avian specific C
terminal extension. Interestingly, ectopic expression of DDX5 rescues the cold
sensitivity, cryptic initiation defects, and impaired glucose import in dbp2Delta
cells, suggesting functional conservation. Consistently, we show that DDX5
promotes glucose uptake and glycolysis in mouse AML12 hepatocyte cells,
suggesting that mammalian DDX5 and S. cerevisiae Dbp2 share conserved roles in
cellular metabolism.
PMID- 28411209
TI - Phylogeography of the wild and cultivated stimulant plant qat (Catha edulis,
Celastraceae) in areas of historical cultivation.
AB - PREMISE OF THE STUDY: Qat (Catha edulis, Celastraceae) is a woody plant species
cultivated for its stimulant alkaloids. Qat is important to the economy and
culture in large regions of Ethiopia, Kenya, and Yemen. Despite the importance of
this species, the wild origins and dispersal of cultivars have only been
described in often contradictory historical documents. We examined the wild
origins, human-mediated dispersal, and genetic divergence of cultivated qat
compared to wild qat. METHODS: We sampled 17 SSR markers and 1561 wild and
cultivated individuals across the historical areas of qat cultivation. KEY
RESULTS: On the basis of genetic structure inferred using Bayesian and
nonparametric methods, two centers of origin in Kenya and one in Ethiopia were
found for cultivated qat. The centers of origin in Ethiopia and northeast of Mt.
Kenya are the primary sources of cultivated qat genotypes. Qat cultivated in
Yemen is derived from Ethiopian genotypes rather than Yemeni wild populations.
Cultivated qat with a wild Kenyan origin has not spread to Ethiopia or Yemen,
whereas a small minority of qat cultivated in Kenya originated in Ethiopia.
Hybrid genotypes with both Ethiopian and Kenyan parentage are present in northern
Kenya. CONCLUSIONS: Ethiopian cultivars have diverged from their wild relatives,
whereas Kenyan qat has diverged less. This pattern of divergence could be caused
by the extinction of the wild-source qat populations in Ethiopia due to
deforestation, undersampling, and/or artificial selection for agronomically
important traits.
PMID- 28411207
TI - Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of
Castration-Resistant Prostate Cancer.
AB - Current treatments for castration-resistant prostate cancer (CRPC) that target
androgen receptor (AR) signaling improve patient survival, yet ultimately fail.
Here, we provide novel insights into treatment response for the antiandrogen
abiraterone by analyses of a genetically engineered mouse (GEM) model with
combined inactivation of Trp53 and Pten, which are frequently comutated in human
CRPC. These NPp53 mice fail to respond to abiraterone and display accelerated
progression to tumors resembling treatment-related CRPC with neuroendocrine
differentiation (CRPC-NE) in humans. Cross-species computational analyses
identify master regulators of adverse response that are conserved with human CRPC
NE, including the neural differentiation factor SOX11, which promotes
neuroendocrine differentiation in cells derived from NPp53 tumors. Furthermore,
abiraterone-treated NPp53 prostate tumors contain regions of focal and/or overt
neuroendocrine differentiation, distinguished by their proliferative potential.
Notably, lineage tracing in vivo provides definitive and quantitative evidence
that focal and overt neuroendocrine regions arise by transdifferentiation of
luminal adenocarcinoma cells. These findings underscore principal roles for TP53
and PTEN inactivation in abiraterone resistance and progression from
adenocarcinoma to CRPC-NE by transdifferentiation.Significance: Understanding
adverse treatment response and identifying patients likely to fail treatment
represent fundamental clinical challenges. By integrating analyses of GEM models
and human clinical data, we provide direct genetic evidence for
transdifferentiation as a mechanism of drug resistance as well as for stratifying
patients for treatment with antiandrogens. Cancer Discov; 7(7); 736-49. (c)2017
AACR.See related commentary by Sinha and Nelson, p. 673This article is
highlighted in the In This Issue feature, p. 653.
PMID- 28411210
TI - Photoperiod throughout the maternal life cycle, not photoperiod during seed
imbibition, influences germination in Arabidopsis thaliana.
AB - PREMISE OF THE STUDY: Plants adjust their phenology in response to seasonal cues
experienced both by their parents and by themselves, and coordinating responses
to these cues is necessary for expressing adaptive phenology. We investigated how
cues are integrated across time to influence an important progeny phenotype,
i.e., seed germination. METHODS: We used Arabidopsis thaliana to investigate how
the photoperiod experienced by maternal parents and by progeny influences seed
germination. We examined when maternal photoperiod effects on germination are
imposed and how long they persist in progeny. KEY RESULTS: The photoperiod
experienced by maternal plants more strongly influenced germination than the
photoperiod experienced during seed imbibition. In addition, the photoperiod
experienced at the prereproductive stage frequently influenced germination as
strongly as that experienced during reproduction. In general, seeds from plants
grown under short days had higher seed germination percentages than seeds from
plants grown in longer days. These maternal effects diminished with after
ripening, but reappeared in seeds induced into secondary dormancy. CONCLUSIONS:
We found no evidence that the effect of photoperiod systematically attenuates in
proportion to the time that elapsed between the cue and the timing of seed
germination. Moreover, more recently experienced cues did not override the
effects of cues experienced previously. Instead, specific sequences of
photoperiods experienced at the prereproductive and reproductive stages appear to
influence germination behavior.
PMID- 28411211
TI - Persistence of endophytic fungi in cultivars of Lolium perenne grown from seeds
stored for 22 years.
AB - PREMISE OF THE STUDY: Genetic resources for forage crops often consist of seeds
of specific species and cultivars in cold storage for future use in breeding and
selection programs. Temperate grasses such as Lolium perenne, used worldwide for
forage and turf, produce seeds commonly infected by hyphae of an endophytic
fungus (Epichloe festucae var. lolii). This research determined whether
endophytes could persist and infect seedlings of L. perenne emerging from seeds
stored for over two decades. METHODS: Endophyte-infected seeds (>90% infected) of
four cultivars were obtained in 1994 and stored dry in plastic bags at 4 degrees
C. Seed germination was tested after 12 yr (for two cultivars) and after 18 and
22 yr (for all cultivars). Seedling leaf sheaths were excised, stained, and
examined at 400* for endophytic hyphae to quantify infection frequency (% plants
infected) and intensity (mean number of endophytic hyphae per field of view). KEY
RESULTS: Seed germination after 22 yr depended on cultivar, ranging from 53 to
78%. Between 58 and 73% of plants grown from seeds stored for 22 yr still
contained viable endophytic hyphae. Infection intensity remained at original
levels for 18 yr in one cultivar; however, in all cultivars, infection intensity
declined significantly between 18 and 22 yr. CONCLUSIONS: Persistence of the
grass seed-endophyte symbiosis for over 20 yr surpasses all prior records of
endophyte longevity within stored seeds. Storage of germplasm of cool-season
grass cultivars that contain potentially beneficial fungal endophytes should be
possible for several decades under dry, cold conditions.
PMID- 28411212
TI - Insights into the effects of complement factor H on the assembly and decay of the
alternative pathway C3 proconvertase and C3 convertase.
PMID- 28411213
TI - Allostery modulates the beat rate of a cardiac pacemaker.
AB - The S672R mutation in heart cell ion channels leads to low heart rates and
arrhythmia by an unknown route. A multifaceted NMR analysis now demonstrates that
this mutant impacts allosteric coupling in domains inside of the cell to change
channel activation, providing a mechanistic explanation for phenotypic outcomes.
PMID- 28411214
TI - Achiral symmetry breaking and positive Gaussian modulus lead to scalloped
colloidal membranes.
AB - In the presence of a nonadsorbing polymer, monodisperse rod-like particles
assemble into colloidal membranes, which are one-rod-length-thick liquid-like
monolayers of aligned rods. Unlike 3D edgeless bilayer vesicles, colloidal
monolayer membranes form open structures with an exposed edge, thus presenting an
opportunity to study elasticity of fluid sheets. Membranes assembled from single
component chiral rods form flat disks with uniform edge twist. In comparison,
membranes composed of a mixture of rods with opposite chiralities can have the
edge twist of either handedness. In this limit, disk-shaped membranes become
unstable, instead forming structures with scalloped edges, where two adjacent
lobes with opposite handedness are separated by a cusp-shaped point defect. Such
membranes adopt a 3D configuration, with cusp defects alternatively located above
and below the membrane plane. In the achiral regime, the cusp defects have
repulsive interactions, but away from this limit we measure effective long-ranged
attractive binding. A phenomenological model shows that the increase in the edge
energy of scalloped membranes is compensated by concomitant decrease in the
deformation energy due to Gaussian curvature associated with scalloped edges,
demonstrating that colloidal membranes have positive Gaussian modulus. A simple
excluded volume argument predicts the sign and magnitude of the Gaussian
curvature modulus that is in agreement with experimental measurements. Our
results provide insight into how the interplay between membrane elasticity,
geometrical frustration, and achiral symmetry breaking can be used to fold
colloidal membranes into 3D shapes.
PMID- 28411215
TI - The effect of Rho drugs on mast cell activation and degranulation.
AB - Mast cells are tissue-resident immune cells that produce potent proinflammatory
mediators, which are stored in cytoplasmic granules. Stimulation triggers
degranulation, a process that mobilizes granules to dock and fuse to the plasma
membrane, releasing mediators. Mast cell degranulation has an important role in
immunity but can also intensify inflammation and contribute to allergic
disorders. Hence, it is important to understand signaling pathways that regulate
mast cell degranulation. Here, we examined the role of Rho proteins in regulating
mast cell activation leading to degranulation. RBL-2H3 cells and bone marrow
derived mast cells (BMMCs) were stimulated through aggregation of FcepsilonRI
receptors. Stimulated cells showed a large increase in the levels of activated
Rac and, to a lesser extent, RhoA. Drugs were used to acutely inhibit the
function of specific Rho proteins. The Rac inhibitor EHT-1864 and the RhoA
inhibitor rhosin inhibited degranulation. Microscopic characterization showed
that, upon stimulation, RBL-2H3 cells formed surface ridges that grew into large
protrusions reminiscent of circular dorsal ruffles, which flattened into large
lamellipodia. LysoTracker-labeled cells showed granules stream into peripheral
protrusions. EHT-1864 reduced granule motility, whereas rhosin increased
motility; both drugs affected the formation of peripheral protrusions. These
results showed that, in response to stimuli, Rho proteins control discrete
cytoskeletal remodeling processes that are needed for granule exocytosis. Rac is
required to stimulate the remodeling of mast cells, triggering actin-mediated
flattening of the cell periphery to create an active degranulation zone, whereas
RhoA controls the streaming of highly motile granules into the active zone.
PMID- 28411216
TI - Construction of a Gene Knockdown System Based on Catalytically Inactive ("Dead")
Cas9 (dCas9) in Staphylococcus aureus.
AB - There has been an absence of an efficient method of gene knockdown in the
important human pathogen Staphylococcus aureus like RNA interference in
eukaryotes. The previously developed antisense RNA technology is mainly applied
for forward genetic screening but is rather limited in specific gene knockdown
because of the lack of rational antisense RNA design strategies. Here we report
an efficient and specific system for gene knockdown in S. aureus based on the
type II clustered regularly interspaced short palindromic repeat (CRISPR) system
from Streptococcus pyogenes We can achieve gene silencing with the coexpression
of dCas9, an RNA-guided DNA binding protein, and a small guide RNA complementary
to the target gene. With this system, we have successfully silenced diverse sets
of genes varying in size and expression level in different S. aureus strains.
This system exhibited high-efficiency knockdown of both essential and
nonessential genes, and its effect is inducible and reversible. In addition, the
system can repress the expression of multiple genes simultaneously and silence an
entire operon or part of it. This RNA-guided DNA targeting system thus provides a
simple, rapid, and affordable method for selective gene knockdown in S.
aureusIMPORTANCEStaphylococcus aureus is an important human and animal pathogen
that can cause a diversity of infectious diseases. Molecular genetic study of S.
aureus has provided an avenue for the understanding of its virulence,
pathogenesis, and drug resistance, leading to the discovery of new therapies for
the treatment of staphylococcal infections. However, methodologies developed for
genetic manipulation of S. aureus usually involve either low efficiency or
laborious procedures. Here we report an RNA-guided system for gene knockdown in
S. aureus and show its high efficiency and simplicity for selective gene
silencing in different strains of S. aureus This simple, rapid, and affordable
system may serve as a promising tool for functional gene study in S. aureus,
especially for the study of essential genes, thus facilitating the understanding
of this pathogen and its interaction with its hosts.
PMID- 28411217
TI - Transfer Potential of Plasmids Conferring Extended-Spectrum-Cephalosporin
Resistance in Escherichia coli from Poultry.
AB - Escherichia coli strains resistant to extended-spectrum cephalosporins (ESC) are
widely distributed in Norwegian broiler production, and the majority harbor
transferable IncK or IncI1 plasmids carrying blaCMY-2 Persistent occurrence in
broiler farms may occur through the survival of ESC-resistant E. coli strains in
the farm environment, or by transfer and maintenance of resistance plasmids
within a population of environmental bacteria with high survival abilities. The
aim of this study was to determine the transferability of two successful blaCMY-2
carrying plasmids belonging to the incompatibility groups IncK and IncI1 into E.
coli and Serratia species recipients. Initially, conjugative plasmid transfer
from two E. coli donors to potential recipients was tested in an agar assay.
Conjugation was further investigated for selected mating pairs in surface and
planktonic assays at temperatures from 12 degrees C to 37 degrees C. Transfer of
plasmids was observed on agar, in broth, and in biofilm at temperatures down to
25 degrees C. The IncK plasmid was able to transfer into Serratia marcescens, and
transconjugants were able to act as secondary plasmid donors to different E. coli
and Serratia species recipients. All transconjugants displayed an AmpC phenotype
corresponding to the acquisition of blaCMY-2 In summary, the results indicate
that the IncK plasmid may transfer between E. coli and Serratia spp. under
conditions relevant for broiler production.IMPORTANCE Certain blaCMY-2-carrying
plasmids are successful and disseminated in European broiler production.
Traditionally, plasmid transferability has been studied under conditions that are
optimal for bacterial growth. Plasmid transfer has previously been reported
between E. coli bacteria in biofilms at 37 degrees C and in broth at temperatures
ranging from 8 to 37 degrees C. However, intergenus transfer of blaCMY-2-carrying
plasmids from E. coli to environmental bacteria in the food-processing chain has
not been previously studied. We demonstrate that blaCMY-2-carrying plasmids are
capable of conjugative transfer between different poultry-associated bacterial
genera under conditions relevant for broiler production. Transfer to Serratia
spp. and to hosts with good biofilm-forming abilities and with the potential to
act as secondary plasmid donors to new hosts might contribute to the persistence
of these resistance plasmids. These results contribute to increased knowledge of
factors affecting the persistence of ESC resistance in broiler production and can
provide a basis for improvement of routines and preventive measures.
PMID- 28411218
TI - The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human
Genome.
AB - Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase
TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at
the oriT gene, covalently attaches to it, and leads the single-stranded DNA
(ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific
integration of the transferred DNA into its target sequence present in the genome
of the recipient bacterium. Here, we report the analysis of the efficiency and
specificity of the integrase activity of TrwC in human cells, using the type IV
secretion system of the human pathogen Bartonella henselae to introduce relaxase
DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC
mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells
and a 100-fold increase in the rate of chromosomal integration of the transferred
DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize
the integration pattern in the human genome. DNA sequence analysis revealed
mostly reconstituted oriT sequences, indicating that TrwC is active and
recircularizes transferred DNA in human cells. One TrwC-mediated site-specific
integration event was detected, proving that TrwC is capable of mediating site
specific integration in the human genome, albeit with very low efficiency
compared to the rate of random integration. Our results suggest that TrwC may
stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by
recircularization of the transferred DNA strand. This stabilization would
increase the opportunities for integration of the DNA by the host
machinery.IMPORTANCE Different biotechnological applications, including gene
therapy strategies, require permanent modification of target cells. Long-term
expression is achieved either by extrachromosomal persistence or by integration
of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC,
a bacterial protein with site-specific integrase activity in bacteria, as an
integrase in human cells. Although it is not efficient as a site-specific
integrase, we found that TrwC is active in human cells and promotes random
integration of the transferred DNA in the human genome, probably acting as a DNA
chaperone until it is integrated by host mechanisms. TrwC-DNA complexes can be
delivered to human cells through a type IV secretion system involved in
pathogenesis. Thus, TrwC could be used in vivo to transfer the DNA of interest
into the appropriate cell and promote its integration. If used in combination
with a site-specific nuclease, it could lead to site-specific integration of the
incoming DNA by homologous recombination.
PMID- 28411219
TI - Global-Scale Structure of the Eelgrass Microbiome.
AB - Plant-associated microorganisms are essential for their hosts' survival and
performance. Yet, most plant microbiome studies to date have focused on
terrestrial species sampled across relatively small spatial scales. Here, we
report the results of a global-scale analysis of microbial communities associated
with leaf and root surfaces of the marine eelgrass Zostera marina throughout its
range in the Northern Hemisphere. By contrasting host microbiomes with those of
surrounding seawater and sediment, we uncovered the structure, composition, and
variability of microbial communities associated with eelgrass. We also
investigated hypotheses about the assembly of the eelgrass microbiome using a
metabolic modeling approach. Our results reveal leaf communities displaying high
variability and spatial turnover that mirror their adjacent coastal seawater
microbiomes. By contrast, roots showed relatively low compositional turnover and
were distinct from surrounding sediment communities, a result driven by the
enrichment of predicted sulfur-oxidizing bacterial taxa on root surfaces.
Predictions from metabolic modeling of enriched taxa were consistent with a
habitat-filtering community assembly mechanism whereby similarity in resource use
drives taxonomic cooccurrence patterns on belowground, but not aboveground, host
tissues. Our work provides evidence for a core eelgrass root microbiome with
putative functional roles and highlights potentially disparate processes
influencing microbial community assembly on different plant
compartments.IMPORTANCE Plants depend critically on their associated microbiome,
yet the structure of microbial communities found on marine plants remains poorly
understood in comparison to that for terrestrial species. Seagrasses are the only
flowering plants that live entirely in marine environments. The return of
terrestrial seagrass ancestors to oceans is among the most extreme habitat shifts
documented in plants, making them an ideal testbed for the study of microbial
symbioses with plants that experience relatively harsh abiotic conditions. In
this study, we report the results of a global sampling effort to extensively
characterize the structure of microbial communities associated with the
widespread seagrass species Zostera marina, or eelgrass, across its geographic
range. Our results reveal major differences in the structure and composition of
above- versus belowground microbial communities on eelgrass surfaces, as well as
their relationships with the environment and host.
PMID- 28411220
TI - The Global Transcription Factor Lrp Is both Essential for and Inhibitory to
Xenorhabdus nematophila Insecticidal Activity.
AB - In the entomopathogenic bacterium Xenorhabdus nematophila, cell-to-cell variation
in the abundance of the Lrp transcription factor leads to virulence modulation;
low Lrp levels are associated with a virulent phenotype and suppression of
antimicrobial peptides (AMPs) in Manduca sexta insects, while cells that lack lrp
or express high Lrp levels are virulence attenuated and elicit AMP expression. To
better understand the basis of these phenotypes, we examined X. nematophila
strains expressing fixed Lrp levels. Unlike the lrp-null mutant, the high-lrp
strain is fully virulent in Drosophila melanogaster, suggesting that these two
strains have distinct underlying causes of virulence attenuation in M. sexta
Indeed, the lrp-null mutant was defective in cytotoxicity against M. sexta
hemocytes relative to that in the high-lrp and low-lrp strains. Further,
supernatant derived from the lrp-null mutant but not from the high-lrp strain was
defective in inhibiting weight gain when fed to 1st instar M. sexta These data
suggest that contributors to the lrp-null mutant virulence attenuation phenotype
are the lack of Lrp-dependent cytotoxic and extracellular oral growth inhibitory
activities, which may be particularly important for virulence in D. melanogaster
In contrast, the high-Lrp strain was sensitive to the antimicrobial peptide
cecropin, had a transient survival defect in M. sexta, and had reduced
extracellular levels of insecticidal activity, measured by injection of
supernatant into 4th instar M. sexta Thus, high-lrp strain virulence attenuation
may be explained by its hypersensitivity to M. sexta host immunity and its
inability to secrete one or more insecticidal factors.IMPORTANCE Adaptation of a
bacterial pathogen to host environments can be achieved through the coordinated
regulation of virulence factors that can optimize success under prevailing
conditions. In the insect pathogen Xenorhabdus nematophila, the global
transcription factor Lrp is necessary for virulence when injected into Manduca
sexta or Drosophila melanogaster insect hosts. However, high levels of Lrp,
either naturally occurring or artificially induced, cause attenuation of X.
nematophila virulence in M. sexta but not D. melanogaster Here, we present
evidence suggesting that the underlying cause of high-Lrp-dependent virulence
attenuation in M. sexta is hypersensitivity to host immune responses and
decreased insecticidal activity and that high-Lrp virulence phenotypes are insect
host specific. This knowledge suggests that X. nematophila faces varied
challenges depending on the type of insect host it infects and that its success
in these environments depends on Lrp-dependent control of a multifactorial
virulence repertoire.
PMID- 28411221
TI - An Extracellular Cell-Attached Pullulanase Confers Branched alpha-Glucan
Utilization in Human Gut Lactobacillus acidophilus.
AB - Of the few predicted extracellular glycan-active enzymes, glycoside hydrolase
family 13 subfamily 14 (GH13_14) pullulanases are the most common in human gut
lactobacilli. These enzymes share a unique modular organization, not observed in
other bacteria, featuring a catalytic module, two starch binding modules, a
domain of unknown function, and a C-terminal surface layer association protein
(SLAP) domain. Here, we explore the specificity of a representative of this group
of pullulanases, Lactobacillus acidophilus Pul13_14 (LaPul13_14), and its role in
branched alpha-glucan metabolism in the well-characterized Lactobacillus
acidophilus NCFM, which is widely used as a probiotic. Growth experiments with L.
acidophilus NCFM on starch-derived branched substrates revealed a preference for
alpha-glucans with short branches of about two to three glucosyl moieties over
amylopectin with longer branches. Cell-attached debranching activity was
measurable in the presence of alpha-glucans but was repressed by glucose. The
debranching activity is conferred exclusively by LaPul13_14 and is abolished in a
mutant strain lacking a functional LaPul13_14 gene. Hydrolysis kinetics of
recombinant LaPul13_14 confirmed the preference for short-branched alpha-glucan
oligomers consistent with the growth data. Curiously, this enzyme displayed the
highest catalytic efficiency and the lowest Km reported for a pullulanase.
Inhibition kinetics revealed mixed inhibition by beta-cyclodextrin, suggesting
the presence of additional glucan binding sites besides the active site of the
enzyme, which may contribute to the unprecedented substrate affinity. The enzyme
also displays high thermostability and higher activity in the acidic pH range,
reflecting adaptation to the physiologically challenging conditions in the human
gut.IMPORTANCE Starch is one of the most abundant glycans in the human diet.
Branched alpha-1,6-glucans in dietary starch and glycogen are nondegradable by
human enzymes and constitute a metabolic resource for the gut microbiota. The
role of health-beneficial lactobacilli prevalent in the human small intestine in
starch metabolism remains unexplored in contrast to colonic bacterial residents.
This study highlights the pivotal role of debranching enzymes in the breakdown of
starchy branched alpha-glucan oligomers (alpha-limit dextrins) by human gut
lactobacilli exemplified by Lactobacillus acidophilus NCFM, which is one of the
best-characterized strains used as probiotics. Our data bring novel insight into
the metabolic preference of L. acidophilus for alpha-glucans with short alpha-1,6
branches. The unprecedented affinity of the debranching enzyme that confers
growth on these substrates reflects its adaptation to the nutrient-competitive
gut ecological niche and constitutes a potential advantage in cross-feeding from
human and bacterial dietary starch metabolism.
PMID- 28411222
TI - Effect of Antimicrobial and Physical Treatments on Growth of Multispecies
Staphylococcal Biofilms.
AB - The prevalence and structure of Staphylococcus aureus and Staphylococcus
epidermidis within multispecies biofilms were found to depend sensitively on
physical environment and antibiotic dosage. Although these species commonly
infect similar sites, such as orthopedic implants, little is known about their
behavior in multispecies communities, particularly in response to treatment. This
research establishes that S. aureus is much more prevalent than S. epidermidis
when simultaneously seeded and grown under unstressed conditions (pH 7, 37
degrees C) in both laboratory and clinical strains. In multispecies communities,
S. epidermidis is capable of growing a more confluent biofilm when the addition
of S. aureus is delayed 4 to 6 h during 18 h of growth. Different vancomycin
dosages generate various behaviors: S. epidermidis is more prevalent at a dose of
1.0 MUg/ml vancomycin, but reduced growth of both species occurs at 1.9 MUg/ml
vancomycin. This variability is consistent with the different MICs of S. aureus
and S. epidermidis Growth at higher temperature (45 degrees C) results in an
environment where S. aureus forms porous biofilms. This porosity allows S.
epidermidis to colonize more of the surface, resulting in detectable S.
epidermidis biomass. Variations in pH result in increased prevalence of S.
epidermidis at low pH (pH 5 and 6), while S. aureus remains dominant at high pH
(pH 8 and 9). This work establishes the structural variability of multispecies
staphylococcal biofilms as they undergo physical and antimicrobial treatments. It
provides a basis for understanding the structure of these communities at
infection sites and how treatments disrupt their multispecies
behaviors.IMPORTANCEStaphylococcus aureus and Staphylococcus epidermidis are two
species of bacteria that are commonly responsible for biofilm infections on
medical devices. Biofilms are structured communities of bacteria surrounded by
polysaccharides, proteins, and DNA; bacteria are more resistant to antimicrobials
as part of a biofilm than as individual cells. This work investigates the
structure and prevalence of these two organisms when grown together in
multispecies biofilms and shows shifts in the behavior of the polymicrobial
community when grown in various concentrations of vancomycin (an antibiotic
commonly used to treat staphylococcal infections), in a high-temperature
environment (a condition previously shown to lead to cell disruption and death),
and at low and high pH (a change that has been previously shown to soften the
mechanical properties of staphylococcal biofilms). These shifts in community
structure demonstrate the effect such treatments may have on multispecies
staphylococcal infections.
PMID- 28411223
TI - Modified Bacteriophage S16 Long Tail Fiber Proteins for Rapid and Specific
Immobilization and Detection of Salmonella Cells.
AB - Bacteriophage-based assays and biosensors rival traditional antibody-based
immunoassays for detection of low-level Salmonella contaminations. In this study,
we harnessed the binding specificity of the long tail fiber (LTF) from
bacteriophage S16 as an affinity molecule for the immobilization, enrichment, and
detection of Salmonella We demonstrate that paramagnetic beads (MBs) coated with
recombinant gp37-gp38 LTF complexes (LTF-MBs) are highly effective tools for
rapid affinity magnetic separation and enrichment of Salmonella Within 45 min,
the LTF-MBs consistently captured over 95% of Salmonella enterica serovar
Typhimurium cells from suspensions containing from 10 to 105 CFU . ml-1, and they
yielded equivalent recovery rates (93% +/- 5%, n = 10) for other Salmonella
strains tested. LTF-MBs also captured Salmonella cells from various food sample
preenrichments, allowing the detection of initial contaminations of 1 to 10 CFU
per 25 g or ml. While plating of bead-captured cells allowed ultrasensitive but
time-consuming detection, the integration of LTF-based enrichment into a sandwich
assay with horseradish peroxidase-conjugated LTF (HRP-LTF) as a detection probe
produced a rapid and easy-to-use Salmonella detection assay. The novel enzyme
linked LTF assay (ELLTA) uses HRP-LTF to label bead-captured Salmonella cells for
subsequent identification by HRP-catalyzed conversion of chromogenic 3,3',5,5'
tetramethylbenzidine substrate. The color development was proportional for
Salmonella concentrations between 102 and 107 CFU . ml-1 as determined by
spectrophotometric quantification. The ELLTA assay took 2 h to complete and
detected as few as 102 CFU . ml-1S Typhimurium cells. It positively identified 21
different Salmonella strains, with no cross-reactivity for other bacteria. In
conclusion, the phage-based ELLTA represents a rapid, sensitive, and specific
diagnostic assay that appears to be superior to other currently available
tests.IMPORTANCE The incidence of foodborne diseases has increased over the
years, resulting in major global public health issues. Conventional methods for
pathogen detection can be laborious and expensive, and they require lengthy
preenrichment steps. Rapid enrichment-based diagnostic assays, such as
immunomagnetic separation, can reduce detection times while also remaining
sensitive and specific. A critical component in these tests is implementing
affinity molecules that retain the ability to specifically capture target
pathogens over a wide range of in situ applications. The protein complex that
forms the distal tip of the bacteriophage S16 long tail fiber is shown here to
represent a highly sensitive affinity molecule for the specific enrichment and
detection of Salmonella Phage-encoded long tail fibers have huge potential for
development as novel affinity molecules for robust and specific diagnostics of a
vast spectrum of bacteria.
PMID- 28411224
TI - Concurrent Haloalkanoate Degradation and Chlorate Reduction by Pseudomonas
chloritidismutans AW-1T.
AB - Haloalkanoates are environmental pollutants that can be degraded aerobically by
microorganisms producing hydrolytic dehalogenases. However, there is a lack of
information about the anaerobic degradation of haloalkanoates. Genome analysis of
Pseudomonas chloritidismutans AW-1T, a facultative anaerobic chlorate-reducing
bacterium, showed the presence of two putative haloacid dehalogenase genes, the l
DEX gene and dehI, encoding an l-2-haloacid dehalogenase (l-DEX) and a
halocarboxylic acid dehydrogenase (DehI), respectively. Hence, we studied the
concurrent degradation of haloalkanoates and chlorate as a yet-unexplored trait
of strain AW-1T The deduced amino acid sequences of l-DEX and DehI revealed 33 to
37% and 26 to 86% identities with biochemically/structurally characterized l-DEX
and the d- and dl-2-haloacid dehalogenase enzymes, respectively. Physiological
experiments confirmed that strain AW-1T can grow on chloroacetate, bromoacetate,
and both l- and d-alpha-halogenated propionates with chlorate as an electron
acceptor. Interestingly, growth and haloalkanoate degradation were generally
faster with chlorate as an electron acceptor than with oxygen as an electron
acceptor. In line with this, analyses of l-DEX and DehI dehalogenase activities
using cell-free extract (CFE) of strain AW-1T grown on dl-2-chloropropionate
under chlorate-reducing conditions showed up to 3.5-fold higher dehalogenase
activity than the CFE obtained from AW-1T cells grown on dl-2-chloropropionate
under aerobic conditions. Reverse transcription-quantitative PCR showed that the
l-DEX gene was expressed constitutively independently of the electron donor
(haloalkanoates or acetate) or acceptor (chlorate or oxygen), whereas the
expression of dehI was induced by haloalkanoates. Concurrent degradation of
organic and inorganic halogenated compounds by strain AW-1T represents a unique
metabolic capacity in a single bacterium, providing a new piece of the puzzle of
the microbial halogen cycle.IMPORTANCE Halogenated organic and inorganic
compounds are important environmental pollutants that have carcinogenic and
genotoxic effects on both animals and humans. Previous research studied the
degradation of organic and inorganic halogenated compounds separately but not
concurrently. This study shows concurrent degradation of halogenated alkanoates
and chlorate as an electron donor and acceptor, respectively, coupled to growth
in a single bacterium, Pseudomonas chloritidismutans AW-1T Hence, besides
biogenesis of molecular oxygen from chlorate reduction enabling a distinctive
placement of strain AW-1T between aerobic and anaerobic microorganisms, we can
now add another unique metabolic potential of this bacterium to the roster. The
degradation of different halogenated compounds under anoxic conditions by a
single bacterium is also of interest for the natural halogen cycle in different
aquatic and terrestrial ecosystems where ample natural production of halogenated
compounds has been documented.
PMID- 28411225
TI - A Genome-Wide Search for Ionizing-Radiation-Responsive Elements in Deinococcus
radiodurans Reveals a Regulatory Role for the DNA Gyrase Subunit A Gene's 5'
Untranslated Region in the Radiation and Desiccation Response.
AB - Tight regulation of gene expression is important for the survival of Deinococcus
radiodurans, a model bacterium of extreme stress resistance. Few studies have
examined the use of regulatory RNAs as a possible contributing mechanism to
ionizing radiation (IR) resistance, despite their proffered efficient and dynamic
gene expression regulation under IR stress. This work presents a transcriptome
based approach for the identification of stress-responsive regulatory 5'
untranslated region (5'-UTR) elements in D. radiodurans R1 that can be broadly
applied to other bacteria. Using this platform and an in vivo fluorescence
screen, we uncovered the presence of a radiation-responsive regulatory motif in
the 5' UTR of the DNA gyrase subunit A gene. Additional screens under H2O2
induced oxidative stress revealed the specificity of the response of this element
to IR stress. Further examination of the sequence revealed a regulatory motif of
the radiation and desiccation response (RDR) in the 5' UTR that is necessary for
the recovery of D. radiodurans from high doses of IR. Furthermore, we suggest
that it is the preservation of predicted RNA structure, in addition to DNA
sequence consensus of the motif, that permits this important regulatory
ability.IMPORTANCEDeinococcus radiodurans is an extremely stress-resistant
bacterium capable of tolerating up to 3,000 times more ionizing radiation than
human cells. As an integral part of the stress response mechanism of this
organism, we suspect that it maintains stringent control of gene expression.
However, understanding of its regulatory pathways remains incomplete to date.
Untranslated RNA elements have been demonstrated to play crucial roles in gene
regulation throughout bacteria. In this work, we focus on searching for and
characterizing responsive RNA elements under radiation stress and propose that
multiple levels of gene regulation work simultaneously to enable this organism to
efficiently recover from exposure to ionizing radiation. The model we propose
serves as a generic template to investigate similar mechanisms of gene regulation
under stress that have likely evolved in other bacterial species.
PMID- 28411226
TI - The Current State of Macrolide Resistance in Campylobacter spp.: Trends and
Impacts of Resistance Mechanisms.
AB - Campylobacter spp., especially Campylobacter jejuni and C. coli, are leading
bacterial foodborne pathogens worldwide. In the United States, an estimated 0.8
million cases of campylobacteriosis occur annually, mostly involving C. jejuni
Campylobacteriosis is generally self-limiting, but in severe cases, treatment
with antibiotics may be mandated. The increasing incidence of fluoroquinolone
resistance in Campylobacter has rendered macrolides such as erythromycin and
azithromycin the drugs of choice for human campylobacteriosis. The prevalence of
macrolide resistance in C. jejuni remains low, but macrolide resistance can be
common in C. coli Substitutions in the 23S rRNA gene, specifically A2075G, and
less frequently A2074C/G, remain the most common mechanism for high-level
resistance to macrolides. In C. jejuni, resistance mediated by such substitutions
is accompanied by a reduced ability to colonize chickens and other fitness costs,
potentially contributing to the low incidence of macrolide resistance.
Interestingly, similar fitness impacts have not been noted in C. coli Also
noteworthy is a novel mechanism first reported in 2014 for a C. coli isolate from
China and mediated by erm(B) harbored on multidrug resistance genomic islands.
The incidence of erm(B) appears to reflect clonal expansion of certain strains,
and whole-genome sequencing has been critical to the elucidation of erm(B)
associated macrolide resistance in Campylobacter spp. With the exception of one
report from Spain, erm(B)-mediated macrolide resistance has been restricted to
Campylobacter spp., mostly C. coli, of animal and human origin from China. If
erm(B)-mediated macrolide resistance does not confer fitness costs in C. jejuni,
the range of this gene may expand in C. jejuni, threatening to compromise
treatment effectiveness for severe campylobacteriosis cases.
PMID- 28411227
TI - Fate and Persistence of a Pathogenic NDM-1-Positive Escherichia coli Strain in
Anaerobic and Aerobic Sludge Microcosms.
AB - The presence of emerging biological pollutants in treated wastewater effluents
has gained attention due to increased interest in water reuse. To evaluate the
effectiveness of the removal of such contaminants by the conventional wastewater
treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli
strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were
assessed in microcosms of anaerobic and aerobic sludge. Results showed that E.
coli PI7 decayed at a significantly lower rate under anaerobic conditions.
Approximate half-lives were 32.4 +/- 1.4 h and 5.9 +/- 0.9 h in the anaerobic and
aerobic microcosms, respectively. In the aerobic microcosms, after 72 h of
operation, E. coli PI7 remained detectable, but no further decay was observed.
Instead, 1 in every 10,000 E. coli cells was identified to be recalcitrant to
decay and persist indefinitely in the sludge. ARGs associated with the E. coli
PI7 strain were detected to have transferred to other native microorganisms in
the sludge or were released to the liquid fraction upon host decay. Extracellular
DNA quickly degraded in the liquid fraction of the aerobic sludge. In contrast,
no DNA decay was detected in the anaerobic sludge water matrix throughout the 24
h sampling period. This study suggests an increased likelihood of environmental
dispersion of ARGs associated with anaerobically treated wastewater effluents and
highlights the potential importance of persister cells in the dissemination of E.
coli in the environment during reuse events of treated wastewater.IMPORTANCE This
study examines the decay kinetics of a pathogenic and antibiotic resistant strain
of Escherichia coli in microcosms simulating biological treatment units of
aerobic and anaerobic sludge. The results of this study point at a significantly
prolonged persistence of the E. coli and the associated antibiotic resistance
gene in the anaerobic sludge. However, horizontal transfer of the plasmid
encoding the antibiotic resistance gene was detected in the aerobic sludge by a
cultivation method. A subpopulation of persister E. coli cells was also detected
in the aerobic sludge. The findings of this study suggest potential areas of
concern arising from pathogenic and antibiotic-resistant E. coli during both
anaerobic and aerobic sludge treatment processes.
PMID- 28411228
TI - Day-to-Day Dynamics of Commensal Escherichia coli in Zimbabwean Cows Evidence
Temporal Fluctuations within a Host-Specific Population Structure.
AB - To get insights into the temporal pattern of commensal Escherichia coli
populations, we sampled the feces of four healthy cows from the same herd in the
Hwange District of Zimbabwe daily over 25 days. The cows had not received
antibiotic treatment during the previous 3 months. We performed viable E. coli
counts and characterized the 326 isolates originating from the 98 stool samples
at a clonal level, screened them for stx and eae genes, and tested them for their
antibiotic susceptibilities. We observed that E. coli counts and dominant clones
were different among cows, and very few clones were shared. No clone was shared
by three or four cows. Clone richness and evenness were not different between
cows. Within each host, the variability in the E. coli count was evidenced
between days, and no clone was found to be dominant during the entire sampling
period, suggesting the existence of clonal interference. Dominant clones tended
to persist longer than subdominant ones and were mainly from phylogenetic groups
A and B1. Five E. coli clones were found to contain both the stx1 and stx2 genes,
representing 6.3% of the studied isolates. All cows harbored at least one Shiga
toxin-producing E. coli (STEC) strain. Resistance to tetracycline, penicillins,
trimethoprim, and sulfonamides was rare and observed in three clones that were
shed at low levels in two cows. This study highlights the fact that the commensal
E. coli population, including the STEC population, is host specific, is highly
dynamic over a short time frame, and rarely carries antibiotic resistance
determinants in the absence of antibiotic treatment.IMPORTANCE The literature
about the dynamics of commensal Escherichia coli populations is very scarce. Over
25 days, we followed the total E. coli counts daily and characterized the sampled
clones in the feces of four cows from the same herd living in the Hwange District
of Zimbabwe. This study deals with the day-to-day dynamics of both quantitative
and qualitative aspects of E. coli commensal populations, with a focus on both
Shiga toxin-producing E. coli and antibiotic-resistant E. coli strains. We show
that the structure of these commensal populations was highly specific to the
host, even though the cows ate and roamed together, and was highly dynamic
between days. Such data are of importance to understand the ecological forces
that drive the dynamics of the emergence of E. coli clones of particular interest
within the gastrointestinal tract and their transmission between hosts.
PMID- 28411230
TI - Interaction of 12/15-lipoxygenase with fatty acids alters the leukocyte kinetics
leading to improved postmyocardial infarction healing.
AB - The metabolic transformation of fatty acids to form oxylipids using 12/15
lipoxygenase (LOX) can promote either resolving or nonresolving inflammation.
However, the mechanism of how 12/15-LOX interacts with polyunsaturated fatty
acids (PUFA) in postmyocardial infarction (post-MI) healing is unclear. Here, we
reported the role of 12/15-LOX in post-MI cardiac remodeling in a PUFA [10%
(wt/wt), 22 kcal]-enriched environment. Wild-type (WT; C57BL/6J) and 12/15-LOX
null (12/15-LOX-/-) male mice of 8-12 wk of age were fed a PUFA-enriched diet for
1 mo and subjected to permanent coronary artery ligation. Post-MI mice were
monitored for day 1 or until day 5 along with standard diet-fed MI controls. No
MI surgery mice served as naive controls. PUFA-fed WT and 12/15-LOX-/- mice
improved ejection fraction and reduced lung edema greater than WT mice at day 5
post-MI (P < 0.05). Post-MI, neutrophil density was decreased in PUFA-fed WT and
12/15-LOX-/- mice at day 1 (P < 0.05). Deletion of 12/15-LOX in mice led to
increased cytochrome P-450-derived bioactive lipid mediator epoxyeicosatrienoic
acids (EETs), i.e., 11,12-EpETrE and 14,15-EpETrE, which were further enhanced by
acute PUFA intake post-MI. Macrophage density was decreased in WT + PUFA and
12/15-LOX-/- mice compared with their respective standard diet-fed WT controls at
day 5 post-MI. 12/15-LOX-/- + PUFA mice displayed an increased expression of
chemokine (C-C motif) ligand 2 and reparative macrophages markers (Ym-1, Mrc-1,
and Arg-1, all P < 0.05) in the infarcted area. Furthermore, 12/15-LOX-/- mice,
with or without PUFA, showed reduced collagen deposition at day 5 post-MI
compared with WT mice. In conclusion, deletion of 12/15-LOX and short-term
exposure of PUFA promoted leukocyte clearance, thereby limiting cardiac
remodeling and promoting an effective resolution of inflammation.NEW & NOTEWORTHY
This study determined that 1) deletion of 12/15-lipoxygenase (LOX) promotes the
generation of epoxyeicosatrienoic acids, the cytochrome P-450-derived metabolites
in postmyocardial infarction (post-MI) healing; 2) acute exposure of fatty acids
to 12/15-LOX-/- mice drives leukocyte (neutrophils and macrophages) clearance
post-MI; and 3) metabolic transformation of fats is the significant contributor
in leukocyte clearance to drive either resolving or nonresolving inflammation
post-MI.
PMID- 28411229
TI - A comprehensive analysis of myocardial substrate preference emphasizes the need
for a synchronized fluxomic/metabolomic research design.
AB - The heart oxidizes fatty acids, carbohydrates, and ketone bodies inside the
tricarboxylic acid (TCA) cycle to generate the reducing equivalents needed for
ATP production. Competition between these substrates makes it difficult to
estimate the extent of pyruvate oxidation. Previously, hyperpolarized pyruvate
detected propionate-mediated activation of carbohydrate oxidation, even in the
presence of acetate. In this report, the optimal concentration of propionate for
the activation of glucose oxidation was measured in mouse hearts perfused in
Langendorff mode. This study was performed with a more physiologically relevant
perfusate than the previous work. Increasing concentrations of propionate did not
cause adverse effects on myocardial metabolism, as evidenced by unchanged O2
consumption, TCA cycle flux, and developed pressures. Propionate at 1 mM was
sufficient to achieve significant increases in pyruvate dehydrogenase flux (3*),
and anaplerosis (6*), as measured by isotopomer analysis. These results further
demonstrate the potential of propionate as an aid for the correct estimation of
total carbohydrate oxidative capacity in the heart. However, liquid
chromotography/mass spectroscopy-based metabolomics detected large changes (~30
fold) in malate and fumarate pool sizes. This observation leads to a key
observation regarding mass balance in the TCA cycle; flux through a portion of
the cycle can be drastically elevated without changing the O2 consumption.
PMID- 28411231
TI - Angiotensin-(1-7) attenuates angiotensin II-induced cardiac hypertrophy via a
Sirt3-dependent mechanism.
AB - The objectives of the present study were to investigate the effect of ANG-(1-7)
on the development of cardiac hypertrophy and to identify the intracellular
mechanism underlying this action of ANG-(1-7). Blood pressure and heart rate were
recorded using radiotelemetry before and after chronic subcutaneous infusion of
control (PBS), ANG II, ANG-(1-7), or ANG II + ANG-(1-7) for 4 wk in normotensive
rats. Chronic administration of ANG-(1-7) did not affect either basal blood
pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1-7)
significantly attenuated ANG II-induced cardiac hypertrophy and perivascular
fibrosis in these rats. These effects of ANG-(1-7) were confirmed in cultured
cardiomyocytes, in which ANG-(1-7) significantly attenuated ANG II-induced
increases in cell size. This protective effect of ANG-(1-7) was significantly
attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a
mitochondria-targeting superoxide scavenger) as well as blockade of Sirt3 (a
deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin
(Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment
with ANG-(1-7) dramatically increased Sirt3 expression. In addition, ANG-(1-7)
attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect
that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1-7) increased FoxO3a
deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA.
In summary, the protective effects of ANG-(1-7) on ANG II-induced cardiac
hypertrophy and increased mitochondrial ROS production are mediated by elevated
SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in
cardiomyocytes. Thus, activation of the ANG-(1-7)/Sirt3 signaling pathway could
be a novel therapeutic strategy in the management of cardiac hypertrophy and
associated complications.NEW & NOTEWORTHY Chronic subcutaneous ANG-(1-7) has no
effect on ANG II-induced elevations in blood pressure but significantly
attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS
dependent mechanism. This protective effect of ANG-(1-7) against the action of
ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of
FoxO3a, which triggers SOD2 expression.
PMID- 28411232
TI - WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in
obese humans.
AB - Experimental studies have suggested that Wingless-related integration site 5A
(WNT5A) is a proinflammatory secreted protein that is associated with metabolic
dysfunction in obesity. Impaired angiogenesis in fat depots has been implicated
in the development of adipose tissue capillary rarefaction, hypoxia,
inflammation, and metabolic dysfunction. We have recently demonstrated that
impaired adipose tissue angiogenesis is associated with overexpression of
antiangiogenic factor VEGF-A165b in human fat and the systemic circulation. In
the present study, we postulated that upregulation of WNT5A is associated with
angiogenic dysfunction and examined its role in regulating VEGF-A165b expression
in human obesity. We biopsied subcutaneous and visceral adipose tissue from 38
obese individuals (body mass index: 44 +/- 7 kg/m2, age: 37 +/- 11 yr) during
planned bariatric surgery and characterized depot-specific protein expression of
VEGF-A165b and WNT5A using Western blot analysis. In both subcutaneous and
visceral fat, VEGF-A165b expression correlated strongly with WNT5A protein (r =
0.9, P < 0.001). In subcutaneous adipose tissue where angiogenic capacity is
greater than in the visceral depot, exogenous human recombinant WNT5A increased
VEGF-A165b expression in both whole adipose tissue and isolated vascular
endothelial cell fractions (P < 0.01 and P < 0.05, respectively). This was
associated with markedly blunted angiogenic capillary sprout formation in human
fat pad explants. Moreover, recombinant WNT5A increased secretion of soluble fms
like tyrosine kinase-1, a negative regulator of angiogenesis, in the sprout media
(P < 0.01). Both VEGF-A165b-neutralizing antibody and secreted frizzled-related
protein 5, which acts as a decoy receptor for WNT5A, significantly improved
capillary sprout formation and reduced soluble fms-like tyrosine kinase-1
production (P < 0.05). We demonstrated a significant regulatory nexus between
WNT5A and antiangiogenic VEGF-A165b in the adipose tissue of obese subjects that
was linked to angiogenic dysfunction. Elevated WNT5A expression in obesity may
function as a negative regulator of angiogenesis.NEW & NOTEWORTHY Wingless
related integration site 5a (WNT5A) negatively regulates adipose tissue
angiogenesis via VEGF-A165b in human obesity.
PMID- 28411233
TI - Vasculopathy in the setting of cardiorenal syndrome: roles of protein-bound
uremic toxins.
AB - Chronic kidney disease (CKD) often leads to and accelerates the progression of
cardiovascular disease (CVD), while CVD also causes kidney dysfunction. This
bidirectional interaction leads to the development of a complex syndrome known as
cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney
but also the vascular system through a vast array of contributing factors. In
addition to hemodynamic, neurohormonal, mechanical, and biochemical factors,
nondialyzable protein-bound uremic toxins (PBUTs) are also key contributing
factors that have been demonstrated through in vitro, in vivo, and clinical
observations. PBUTs are ineffectively removed by hemodialysis because their
complexes with albumins are larger than the pores of the dialysis membranes.
PBUTs such as indoxyl sulfate and p-cresyl sulfate are key determinate and
predictive factors for the progression of CVD in CKD patients. In CRS, both
vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) exhibit
significant dysfunction that is associated with the progression of CVD. PBUTs
influence proliferation, calcification, senescence, migration, inflammation, and
oxidative stress in VSMCs and ECs through various mechanisms. These pathological
changes lead to arterial remodeling, stiffness, and atherosclerosis and thus
reduce heart perfusion and impair left ventricular function, aggravating CRS.
There is limited literature about the effect of PBUT on the vascular system and
their contribution to CRS. This review summarizes current knowledge on how PBUTs
influence vasculature, clarifies the relationship between uremic toxin-related
vascular disease and CRS, and highlights the potential therapeutic strategies of
uremic vasculopathy in the setting of CRS.
PMID- 28411234
TI - Phenotype of GABA-transaminase deficiency.
AB - OBJECTIVE: We report a case series of 10 patients with gamma-aminobutyric acid
(GABA)-transaminase deficiency including a novel therapeutic trial and an
expanded phenotype. METHODS: Case ascertainment, literature review, comprehensive
evaluations, and long-term treatment with flumazenil. RESULTS: All patients
presented with neonatal or early infantile-onset encephalopathy; other features
were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated
linear growth. EEGs showed burst-suppression, modified hypsarrhythmia, multifocal
spikes, and generalized spike-wave. Five of the 10 patients are currently alive
with age at last follow-up between 18 months and 9.5 years. Treatment with
continuous flumazenil was implemented in 2 patients. One patient, with a milder
phenotype, began treatment at age 21 months and has continued for 20 months with
improved alertness and less excessive adventitious movements. The second patient
had a more severe phenotype and was 7 years of age at initiation of flumazenil,
which was not continued. CONCLUSIONS: GABA-transaminase deficiency presents with
neonatal or infantile-onset encephalopathy including hypersomnolence and
choreoathetosis. A widened phenotypic spectrum is reported as opposed to
lethality by 2 years of age. The GABA-A benzodiazepine receptor antagonist
flumazenil may represent a therapeutic strategy.
PMID- 28411235
TI - Anticoagulant and antiplatelet use in seniors with chronic subdural hematoma:
Systematic review.
AB - OBJECTIVE: To address whether to restart older patients on anticoagulants or
antiplatelet agents in the setting of a chronic subdural hematoma (cSDH).
METHODS: This is an update of a previous review (searched until July 2012).
Medline, EMBASE, ISI Web of Knowledge, Google Scholar, PLOS, and the Cochrane
Register for Systematic Reviews databases were searched from January 2012 to
December 2016. Studies included older adults (those over 65 years) experiencing
traumatic subdural hematoma or cSDH who were on anticoagulation or antiplatelet
agents. RESULTS: Seven studies were included (mean age 72 years). Four out of 7
studies provided combined data on anticoagulants or antiplatelet use. Only one
study found anticoagulant or antiplatelet agent use to be a significant factor
for cSDH rebleeding. Two studies considered anticoagulant use only and both
reported similar increased odds of rebleeding (odds ratio [OR] 1.75, 95%
confidence interval [CI] 0.18-16.86; OR 2.7 95% CI 1.42-6.96). Antiplatelets were
not found to be associated with rebleeding. Ideal timing to resume anticoagulants
or antiplatelets was unclear. CONCLUSIONS: Anticoagulant medication was
associated with increased rebleeding risk in older adults with cSDH. However,
antiplatelet medication was not associated with increased risk of rebleeding.
PMID- 28411236
TI - Thromboembolism prevention after chronic subdural hematoma in the elderly: A leap
in the dark.
PMID- 28411237
TI - Physical interaction between human ribonucleotide reductase large subunit and
thioredoxin increases colorectal cancer malignancy.
AB - Ribonucleotide reductase (RR) is the rate-limiting enzyme in DNA synthesis,
catalyzing the reduction of ribonucleotides to deoxyribonucleotides. During each
enzymatic turnover, reduction of the active site disulfide in the catalytic large
subunit is performed by a pair of shuttle cysteine residues in its C-terminal
tail. Thioredoxin (Trx) and glutaredoxin (Grx) are ubiquitous redox proteins,
catalyzing thiol-disulfide exchange reactions. Here, immunohistochemical
examination of clinical colorectal cancer (CRC) specimens revealed that human
thioredoxin1 (hTrx1), but not human glutaredoxin1 (hGrx1), was up-regulated along
with human RR large subunit (RRM1) in cancer tissues, and the expression levels
of both proteins were correlated with cancer malignancy stage. Ectopically
expressed hTrx1 significantly increased RR activity, DNA synthesis, and cell
proliferation and migration. Importantly, inhibition of both hTrx1 and RRM1
produced a synergistic anticancer effect in CRC cells and xenograft mice.
Furthermore, hTrx1 rather than hGrx1 was the efficient reductase for RRM1
regeneration. We also observed a direct protein-protein interaction between RRM1
and hTrx1 in CRC cells. Interestingly, besides the known two conserved cysteines,
a third cysteine (Cys779) in the RRM1 C terminus was essential for RRM1
regeneration and binding to hTrx1, whereas both Cys32 and Cys35 in hTrx1 played a
counterpart role. Our findings suggest that the up-regulated RRM1 and hTrx1 in
CRC directly interact with each other and promote RR activity, resulting in
enhanced DNA synthesis and cancer malignancy. We propose that the RRM1-hTrx1
interaction might be a novel potential therapeutic target for cancer treatment.
PMID- 28411238
TI - Characterization of protein complexes of the endoplasmic reticulum-associated
degradation E3 ubiquitin ligase Hrd1.
AB - Hrd1 is the core structural component of a large endoplasmic reticulum membrane
embedded protein complex that coordinates the destruction of folding-defective
proteins in the early secretory pathway. Defining the composition, dynamics, and
ultimately, the structure of the Hrd1 complex is a crucial step in understanding
the molecular basis of glycoprotein quality control but has been hampered by the
lack of suitable techniques to interrogate this complex under native conditions.
In this study we used genome editing to generate clonal HEK293 (Hrd1.KI) cells
harboring a homozygous insertion of a small tandem affinity tag knocked into the
endogenous Hrd1 locus. We found that steady-state levels of tagged Hrd1 in these
cells are indistinguishable from those of Hrd1 in unmodified cells and that the
tagged variant is functional in supporting the degradation of well characterized
luminal and membrane substrates. Analysis of detergent-solubilized Hrd1.KI cells
indicates that the composition and stoichiometry of Hrd1 complexes are strongly
influenced by Hrd1 expression levels. Analysis of affinity-captured Hrd1
complexes from these cells by size-exclusion chromatography, immunodepletion, and
absolute quantification mass spectrometry identified two major high-molecular
mass complexes with distinct sets of interacting proteins and variable
stoichiometries, suggesting a hitherto unrecognized heterogeneity in the
functional units of Hrd1-mediated protein degradation.
PMID- 28411239
TI - Discrimination of cytosolic self and non-self RNA by RIG-I-like receptors.
AB - RIG-I-like receptors (RLRs) are cytosolic innate immune sensors that detect
pathogenic RNA and induce a systemic antiviral response. During the last decade,
many studies focused on their molecular characterization and the identification
of RNA agonists. Therefore, it became more and more clear that RLR activation
needs to be carefully regulated, because constitutive signaling or detection of
endogenous RNA through loss of specificity is detrimental. Here, we review the
current understanding of RLR activation and selectivity. We specifically focus
upon recent findings on the function of the helicase domain in discriminating
between different RNAs, and whose malfunctioning causes serious autoimmune
diseases.
PMID- 28411240
TI - Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039.
AB - Programmed cell death or apoptosis of infected host cells is an important defense
mechanism in response to viral infections. This process is regulated by
proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein
family. To counter premature death of a virus-infected cell, poxviruses use a
range of different molecular strategies including the mimicry of prosurvival Bcl
2 proteins. One such viral prosurvival protein is the fowlpox virus protein
FPV039, which is a potent apoptosis inhibitor, but the precise molecular
mechanism by which FPV039 inhibits apoptosis is unknown. To understand how
fowlpox virus inhibits apoptosis, we examined FPV039 using isothermal titration
calorimetry, small-angle X-ray scattering, and X-ray crystallography. Here, we
report that the fowlpox virus prosurvival protein FPV039 promiscuously binds to
cellular proapoptotic Bcl-2 and engages all major proapoptotic Bcl-2 proteins.
Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with
cellular proapoptotic Bcl-2 with affinities comparable with those of Bcl-2's
endogenous cellular counterparts. Structural studies revealed that FPV039 adopts
the conserved Bcl-2 fold observed in cellular prosurvival Bcl-2 proteins and
closely mimics the structure of the prosurvival Bcl-2 family protein Mcl-1. Our
findings suggest that FPV039 is a pan-Bcl-2 protein inhibitor that can engage all
host BH3-only proteins, as well as Bcl-2-associated X, apoptosis regulator (Bax)
and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an
infected host cell. This work therefore provides a mechanistic platform to better
understand FPV039-mediated apoptosis inhibition.
PMID- 28411241
TI - 2-Alkylquinolone alkaloid biosynthesis in the medicinal plant Evodia rutaecarpa
involves collaboration of two novel type III polyketide synthases.
AB - 2-Alkylquinolone (2AQ) alkaloids are pharmaceutically and biologically important
natural products produced by both bacteria and plants, with a wide range of
biological effects, including antibacterial, cytotoxic, anticholinesterase, and
quorum-sensing signaling activities. These diverse activities and 2AQ occurrence
in vastly different phyla have raised much interest in the biosynthesis pathways
leading to their production. Previous studies in plants have suggested that type
III polyketide synthases (PKSs) might be involved in 2AQ biosynthesis, but this
hypothesis is untested. To this end, we cloned two novel type III PKSs,
alkyldiketide-CoA synthase (ADS) and alkylquinolone synthase (AQS), from the 2AQ
producing medicinal plant, Evodia rutaecarpa (Rutaceae). Functional analyses
revealed that collaboration of ADS and AQS produces 2AQ via condensations of N
methylanthraniloyl-CoA, a fatty acyl-CoA, with malonyl-CoA. We show that ADS
efficiently catalyzes the decarboxylative condensation of malonyl-CoA with a
fatty acyl-CoA to produce an alkyldiketide-CoA, whereas AQS specifically
catalyzes the decarboxylative condensation of an alkyldiketide acid with N
methylanthraniloyl-CoA to generate the 2AQ scaffold via C-C/C-N bond formations.
Remarkably, the ADS and AQS crystal structures at 1.80 and 2.20 A resolutions,
respectively, indicated that the unique active-site architecture with Trp-332 and
Cys-191 and the novel CoA-binding tunnel with Tyr-215 principally control the
substrate and product specificities of ADS and AQS, respectively. These results
provide additional insights into the catalytic versatility of the type III PKSs
and their functional and evolutionary implications for 2AQ biosynthesis in plants
and bacteria.
PMID- 28411242
TI - Differences in Short- and Long-Term Mortality Associated With BMI Following
Coronary Revascularization.
AB - BACKGROUND: The association between obesity and mortality risks following
coronary revascularization is not clear. We examined the associations of BMI
(kg/m2) with short-, intermediate-, and long-term mortality following coronary
artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI)
in patients with different coronary anatomy risks and diabetes mellitus status.
METHODS AND RESULTS: Data from the Alberta Provincial Project for Outcomes
Assessment in Coronary Heart Disease (APPROACH) registry were analyzed. Using
normal BMI (18.5-24.9) as a reference, multivariable-adjusted hazard ratios for
all-cause mortality within 6 months, 1 year, 5 years, and 10 years were
individually calculated for CABG and PCI with 4 prespecified BMI categories:
overweight (25.0-29.9), obese class I (30.0-34.9), obese class II (35.0-39.9),
and obese class III (>=40.0). The analyses were repeated after stratifying for
coronary risks and diabetes mellitus status. The cohorts included 7560 and 30 258
patients for CABG and PCI, respectively. Following PCI, overall mortality was
lower in patients with overweight and obese class I compared to those with normal
BMI; however, 5- and 10-year mortality rates were significantly higher in
patients with obese class III with high-risk coronary anatomy, which was
primarily driven by higher mortality rates in patients without diabetes mellitus
(5-year adjusted hazard ratio, 1.78 [95% CI, 1.11-2.85] and 10-year adjusted
hazard ratio, 1.57 [95% CI, 1.02-2.43]). Following CABG, overweight was
associated with lower mortality risks compared with normal BMI. CONCLUSIONS:
Overweight was associated with lower mortality following CABG and PCI. Greater
long-term mortality in patients with obese class III following PCI, especially in
those with high-risk coronary anatomy without diabetes mellitus, warrants further
investigation.
PMID- 28411243
TI - Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression
and Instability: Reversal by its Receptor GPR54 Antagonist.
AB - BACKGROUND: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of
angiogenesis, and its receptor, GPR54, have currently received much attention in
relation to pre-eclampsia. However, it still remains unknown whether KP-10 could
affect atherogenesis. METHODS AND RESULTS: We evaluated the effects of KP-10 on
human umbilical vein endothelial cells, human monocyte-derived macrophages, human
aortic smooth muscle cells in vitro, and atherosclerotic lesions in
apolipoprotein E-deficient (ApoE-/-) mice in vivo. KP-10 significantly increased
the adhesion of human monocytes to human umbilical vein endothelial cells, which
was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10
stimulated mRNA expression of tumor necrosis factor-alpha, interleukin-6,
monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular
adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP
10 significantly enhanced oxidized low-density lipoprotein-induced foam cell
formation associated with upregulation of CD36 and acyl-CoA:cholesterol
acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth
muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and
proliferation, but enhanced apoptosis and activities of matrix metalloproteinase
(MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and
2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10
into ApoE-/- mice significantly accelerated the development of aortic
atherosclerotic lesions with increased monocyte/macrophage infiltration and
vascular inflammation as well as decreased intraplaque vascular smooth muscle
cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were
completely canceled by P234 infusion in ApoE-/- mice. CONCLUSIONS: Our results
suggest that KP-10 may contribute to accelerate the progression and instability
of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be
useful for prevention and treatment of atherosclerosis. Thus, the KP-10/GPR54
system may serve as a novel therapeutic target for atherosclerotic diseases.
PMID- 28411244
TI - Long-Term Follow-up of the PADI Trial: Percutaneous Transluminal Angioplasty
Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia.
AB - BACKGROUND: Clinical outcomes reported after treatment of infrapopliteal lesions
with drug-eluting stents (DESs) have been more favorable compared with
percutaneous transluminal angioplasty with a bailout bare metal stent (PTA-BMS)
through midterm follow-up in patients with critical limb ischemia. In the present
study, long-term results of treatment of infrapopliteal lesions with DESs are
presented. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford
category >=4) and infrapopliteal lesions were randomized to receive PTA-BMS or
DESs with paclitaxel. Long-term follow-up consisted of annual assessments up to 5
years after treatment or until a clinical end point was reached. Clinical end
points were major amputation (above ankle level), infrapopliteal surgical or
endovascular reintervention, and death. Preserved primary patency (<=50%
restenosis) of treated lesions was an additional morphological end point,
assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with
DESs and 66 limbs (64 patients) were treated with PTA-BMS. The estimated 5-year
major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA-BMS;
P=0.091). The 5-year rates of amputation- and event-free survival (survival free
from major amputation or reintervention) were significantly higher in the DES arm
compared with PTA-BMS (31.8% versus 20.4%, P=0.043; and 26.2% versus 15.3%,
P=0.041, respectively). Survival rates were comparable. The limited available
morphological results showed higher preserved patency rates after DESs than after
PTA-BMS at 1, 3, and 4 years of follow-up. CONCLUSIONS: Both clinical and
morphological long-term results after treatment of infrapopliteal lesions in
patients with critical limb ischemia are improved with DES compared with PTA-BMS.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT00471289.
PMID- 28411245
TI - Characteristics of Earlier Versus Delayed Presentation of Very Late Drug-Eluting
Stent Thrombosis: An Optical Coherence Tomographic Study.
AB - BACKGROUND: The pathophysiology underlying very late drug-eluting stent (DES)
thrombosis is not sufficiently understood. Using optical coherence tomography, we
investigated characteristics of very late stent thrombosis (VLST) according to
different onset times. METHODS AND RESULTS: A total of 98 patients from 10 South
Korean hospitals who underwent optical coherence tomography for evaluation of
very late DES thrombosis were retrospectively included in analyses. VLST occurred
at a median of 55.1 months after DES implantation. All patients were divided into
2 equal groups of earlier versus delayed presentation of VLST, according to
median onset time. In total, 27 patients were treated with next-generation DES
and 71 with first-generation DES. Based on optical coherence tomography findings
at thrombotic sites, main VLST mechanisms were as follows, in descending order:
neoatherosclerosis (34.7%), stent malapposition (33.7%), and uncovered struts
without stent malapposition or evagination (24.5%). Compared with patients with
earlier VLST, patients with delayed VLST had lower frequency of uncovered struts
without stent malapposition or evagination (34.7% versus 14.3%, respectively;
P=0.019). Conversely, the frequency of neoatherosclerosis was higher in patients
with delayed versus earlier VLST (44.9% versus 24.5%, respectively; P=0.034). The
frequency of stent malapposition was not different between patients with earlier
and delayed VLST (34.7% versus 32.7%, respectively; P=0.831). The frequency of
stent malapposition, evagination, and uncovered struts was still half of delayed
VLST. CONCLUSIONS: The pathological mechanisms of very late DES thrombosis
changed over time. Delayed neointimal healing remained a substantial substrate
for VLST, even long after DES implantation.
PMID- 28411246
TI - Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is
Associated With Increased Risk of Major Bleeding.
AB - BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major
bleeding when measured at initial presentation in patients with acute coronary
syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether
follow-up measurements provide additional information. The objective of this
study was to investigate whether GDF-15 measured 1 month after an ACS provides
additional information beyond the baseline levels with regard to the risk of
major bleeding. METHODS AND RESULTS: GDF-15 was measured at baseline and at 1
month after an ACS in 4049 patients included in the PLATelet inhibition and
patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and
non-coronary artery bypass grafting surgery-related major bleeding was assessed
by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia,
impaired renal function, history of gastrointestinal bleeding, and sex. Elevated
GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non
coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard
ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had
elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month
had a similar risk as patients who had nonelevated levels at both measurements.
CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding
during DAPT and provides additional information on the bleeding risk beyond
baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision
support concerning long-term antithrombotic treatment in patients post-ACS.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT00391872.
PMID- 28411248
TI - State of the art thoracic ultrasound: intervention and therapeutics.
AB - The use of thoracic ultrasound outside the radiology department and in everyday
clinical practice is becoming increasingly common, having been incorporated into
standards of care for many specialties. For the majority of practitioners, their
experience of, and exposure to, thoracic ultrasound will be in its use as an
adjunct to pleural and thoracic interventions, owing to the widely recognised
benefits for patient safety and risk reduction. However, as clinicians become
increasingly familiar with the capabilities of thoracic ultrasound, new
directions for its use are being sought which might enhance practice and patient
care. This article reviews the ways in which the advent of thoracic ultrasound is
changing the approach to the investigation and treatment of respiratory disease
from an interventional perspective. This will include the impact of thoracic
ultrasound on areas including patient safety, diagnostic and therapeutic
procedures, and outcome prediction; and will also consider potential future
research and clinical directions.
PMID- 28411247
TI - Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning.
AB - BACKGROUND: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute
myocardial infarction by distinctive macrophage (Mphi) polarization. Here we
demonstrate that CDC-secreted exosomes (CDCexo) recapitulate the cardioprotective
effects of CDC therapy known as cellular postconditioning. METHODS: Rats and pigs
underwent myocardial infarction induced by ischemia/reperfusion before
intracoronary infusion of CDCexo, inert fibroblast exosomes (Fbexo; control), or
vehicle. Two days later, infarct size was quantified. Macrophages were isolated
from cardiac tissue or bone marrow for downstream analyses. RNA sequencing was
used to determine exosome content and alterations in gene expression profiles in
Mphi. RESULTS: Administration of CDCexo but not Fbexo after reperfusion reduces
infarct size in rat and pig models of myocardial infarction. Furthermore, CDCexo
reduce the number of CD68+ Mphi within infarcted tissue and modify the
polarization state of Mphi so as to mimic that induced by CDCs. CDCexo are
enriched in several miRNAs (including miR-146a, miR-181b, and miR-126) relative
to Fbexo. Reverse pathway analysis of whole-transcriptome data from CDCexo-primed
Mphi implicated miR-181b as a significant (P=1.3x10-21) candidate mediator of CDC
induced Mphi polarization, and PKCdelta (protein kinase C delta) as a downstream
target. Otherwise inert Fbexo loaded selectively with miR-181b alter Mphi
phenotype and confer cardioprotective efficacy in a rat model of myocardial
infarction. Adoptive transfer of PKCdelta-suppressed Mphi recapitulates
cardioprotection. CONCLUSIONS: Our data support the hypothesis that exosomal
transfer of miR-181b from CDCs into Mphi reduces PKCdelta transcript levels and
underlies the cardioprotective effects of CDCs administered after reperfusion.
PMID- 28411249
TI - Endoscopic advanced imaging of the respiratory tract: exploring probe-based
confocal laser endomicroscopy in emphysema.
AB - : : Probe-based confocal laser endomicroscopy (pCLE) was performed in 15 patients
with emphysema and 15 healthy subjects to visualise small airways in a direct and
dynamic way. Morphometry shows that the median cross-sectional area of the
alveolar openings at the level of the alveolar ducts is significantly larger in
emphysema (7.2*104 um2) as compared with healthy subjects (5.2*104 um2)
(p=0.0002). Normalised autofluorescence intensity histograms show a decrease in
median autofluorescence intensity (mAFI) in emphysema (p=0.001). mAFI correlates
well with Tiffeneau index (r=0.66, p=0.007, 95% CI 0.21 to 0.88).
Autofluorescence intensity in emphysema correlates with corresponding data of CT
based quantification. pCLE-based morphometry and autofluorescence intensity
analysis in emphysema is able to detect regional changes inside the 'quiet zone'.
TRIAL REGISTRATION NUMBER: Results, NCT01204970.
PMID- 28411250
TI - Visualising early lung disease in CF: the emergence of MRI.
PMID- 28411251
TI - An extracellular matrix signature in leukemia precursor cells and acute myeloid
leukemia.
PMID- 28411252
TI - Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome
18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker
Consortium.
AB - In follicular lymphoma, studies addressing the prognostic value of
microenvironment-related immunohistochemical markers and tumor cell-related
genetic markers have yielded conflicting results, precluding implementation in
practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a
validation study evaluating published markers. To maximize sensitivity, an end of
spectrum design was applied for 122 uniformly immunochemotherapy-treated
follicular lymphoma patients retrieved from international trials and registries.
The criteria were: early failure, progression or lymphoma-related death <2 years
versus long remission, response duration of >5 years. Immunohistochemical
staining for T cells and macrophages was performed on tissue microarrays from
initial biopsies and scored with a validated computer-assisted protocol. Shallow
whole-genome and deep targeted sequencing was performed on the same samples. The
96/122 cases with complete molecular and immunohistochemical data were included
in the analysis. EZH2 wild-type (P=0.006), gain of chromosome 18 (P=0.002), low
percentages of CD8+ cells (P=0.011) and CD163+ areas (P=0.038) were associated
with early failure. No significant differences in other markers were observed,
thereby refuting previous claims of their prognostic significance. Using an
optimized study design, this Lunenburg Lymphoma Biomarker Consortium study
substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of
CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy
in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic
impact of various other markers.
PMID- 28411253
TI - A new path to platelet production through matrix sensing.
AB - Megakaryocytes (MK) in the bone marrow (BM) are immersed in a network of
extracellular matrix components that regulates platelet release into the
circulation. Combining biological and bioengineering approaches, we found that
the activation of transient receptor potential cation channel subfamily V member
4 (TRPV4), a mechano-sensitive ion channel, is induced upon MK adhesion on softer
matrices. This response promoted platelet production by triggering a cascade of
events that lead to calcium influx, beta1 integrin activation and
internalization, and Akt phosphorylation, responses not found on stiffer
matrices. Lysyl oxidase (LOX) is a physiological modulator of BM matrix stiffness
via collagen crosslinking. In vivo inhibition of LOX and consequent matrix
softening lead to TRPV4 activation cascade and increased platelet levels. At the
same time, in vitro proplatelet formation was reduced on a recombinant enzyme
mediated stiffer collagen. These results suggest a novel mechanism by which MKs,
through TRPV4, sense extracellular matrix environmental rigidity and release
platelets accordingly.
PMID- 28411254
TI - Safety and efficacy of romiplostim in splenectomized and nonsplenectomized
patients with primary immune thrombocytopenia.
AB - Primary immune thrombocytopenia is an autoimmune disorder characterized by
increased platelet destruction and insufficient platelet production without
another identified underlying disorder. Splenectomy may alter responsiveness to
treatment and/or increase the risk of thrombosis, infection, and pulmonary
hypertension. The analysis herein evaluated the safety and efficacy of the
thrombopoietin receptor agonist romiplostim in splenectomized and
nonsplenectomized adults with primary immune thrombocytopenia. Data were pooled
across 13 completed clinical studies in adults with immune thrombocytopenia from
2002-2014. Adverse event rates were adjusted for time of exposure. Results were
considered different when 95% confidence intervals were non-overlapping. Safety
was analyzed for 1111 patients (395 splenectomized; 716 nonsplenectomized) who
received romiplostim or control (placebo or standard of care). At baseline,
splenectomized patients had a longer median duration of immune thrombocytopenia
and a lower median platelet count, as well as a higher proportion with >3 prior
immune thrombocytopenia treatments versus nonsplenectomized patients. In each
treatment group, splenectomized patients used rescue medications more often than
nonsplenectomized patients. Platelet response rates (>=50*109/L) for romiplostim
were 82% (310/376) for splenectomized and 91% (592/648) for nonsplenectomized
patients (P<0.001 by Cochran-Mantel-Haenszel test). Platelet responses were
stable over time in both subgroups. Exposure-adjusted adverse event rates were
higher for control versus romiplostim for both splenectomized (1857 versus 1226
per 100 patient-years) and nonsplenectomized patients (1052 versus 852 per 100
patient-years). In conclusion, responses to romiplostim were seen in both
splenectomized and nonsplenectomized patients, and romiplostim was not associated
with an increase in the risk of adverse events in splenectomized patients.
clinicaltrials.gov Identifier: 00111475(A)(B), 00117143, 00305435, 01143038,
00102323, 00102336, 00415532, 00603642, 00508820, 00907478, 00116688, and
00440037.
PMID- 28411255
TI - Absence of the spleen and the occurrence of primary red cell alloimmunization in
humans.
PMID- 28411256
TI - Epigenetically induced ectopic expression of UNCX impairs the proliferation and
differentiation of myeloid cells.
AB - We here describe a leukemogenic role of the homeobox gene UNCX, activated by
epigenetic modifications in acute myeloid leukemia (AML). We found the ectopic
activation of UNCX in a leukemia patient harboring a t(7;10)(p22;p14)
translocation, in 22 of 61 of additional cases [a total of 23 positive patients
out of 62 (37.1%)], and in 6 of 75 (8%) of AML cell lines. UNCX is embedded
within a low-methylation region (canyon) and encodes for a transcription factor
involved in somitogenesis and neurogenesis, with specific expression in the eye,
brain, and kidney. UNCX expression turned out to be associated, and significantly
correlated, with DNA methylation increase at its canyon borders based on data in
our patients and in archived data of patients from The Cancer Genome Atlas. UNCX
positive and -negative patients displayed significant differences in their gene
expression profiles. An enrichment of genes involved in cell proliferation and
differentiation, such as MAP2K1 and CCNA1, was revealed. Similar results were
obtained in UNCX-transduced CD34+ cells, associated with low proliferation and
differentiation arrest. Accordingly, we showed that UNCX expression characterizes
leukemia cells at their early stage of differentiation, mainly M2 and M3 subtypes
carrying wild-type NPM1 We also observed that UNCX expression significantly
associates with an increased frequency of acute promyelocytic leukemia with PML
RARA and AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 classes, according to the
World Health Organization disease classification. In summary, our findings
suggest a novel leukemogenic role of UNCX, associated with epigenetic
modifications and with impaired cell proliferation and differentiation in AML.
PMID- 28411257
TI - Relief of Pain-Depressed Behavior in Rats by Activation of D1-Like Dopamine
Receptors.
AB - Clinically significant pain often includes a decrease in both behavior and
mesolimbic dopamine signaling. Indirect and/or direct dopamine receptor agonists
may alleviate pain-related behavioral depression. To test this hypothesis, the
present study compared effects of indirect and direct dopamine agonists in a
preclinical assay of pain-depressed operant responding. Male Sprague-Dawley rats
with chronic indwelling microelectrodes in the medial forebrain bundle were
trained in an intracranial self-stimulation (ICSS) procedure to press a lever for
pulses of electrical brain stimulation. Intraperitoneal injection of dilute
lactic acid served as an acute noxious stimulus to depress ICSS. Intraperitoneal
lactic acid-induced depression of ICSS was dose-dependently blocked by the
dopamine transporter inhibitor methylphenidate and the D1-selective agonist
SKF82958, but not by the D2/3-selective agonists quinpirole, pramipexole, or
sumanirole. The antinociceptive effects of methylphenidate and SKF82958 were
blocked by the D1-selective antagonist SCH39166. Acid-induced stimulation of a
stretching response was evaluated in separate groups of rats, but all agonists
decreased acid-stimulated stretching, and antagonism experiments were
inconclusive due to direct effects of the antagonists when administered alone.
Taken together, these results suggest that D1-receptor stimulation is both
sufficient to block acid-induced depression of ICSS and necessary for
methylphenidate antinociception in this procedure. Conversely, D2/3-receptor
stimulation is not sufficient to relieve pain-depressed behavior. These results
support the hypothesis that pain-related depression of dopamine D1 receptor
signaling contributes to pain-related depression of behavior in rats.
Additionally, these results support further consideration of indirect dopamine
agonists and direct D1 receptor agonists as candidate treatments for pain-related
behavioral depression.
PMID- 28411258
TI - Patient With Severe Moyamoya Disease Who Presents With Acute Cortical Blindness.
PMID- 28411259
TI - Cerebral Embolic Protection Devices During Transcatheter Aortic Valve
Implantation: Systematic Review and Meta-Analysis.
AB - BACKGROUND AND PURPOSE: Silent ischemic embolic lesions are common after
transcatheter aortic valve implantation (TAVI). The use of embolic protection
devices (EPD) may reduce the occurrence of these embolic lesions. Thus, a
quantitative overview and credibility assessment of the literature was necessary
to draw a robust message about EPD. Therefore, the aim of this meta-analysis was
to study whether the use of EPD reduces silent ischemic and clinically evident
cerebrovascular events associated with TAVI. METHODS: We conducted a
comprehensive search to identify studies that evaluated patients undergoing TAVI
with or without EPD. Random-effects meta-analyses were performed to estimate the
effect of EPD compared with no-EPD during TAVI using aggregate data. RESULTS:
Sixteen studies involving 1170 patients (865/305 with/without EPD) fulfilled the
inclusion criteria. The EPD delivery success rate was reported in all studies and
was achieved in 94.5% of patients. Meta-analyses evaluating EPD versus without
EPD strategies could not confirm or exclude any differences in terms of
clinically evident stroke (relative risk, 0.70; 95% confidence interval [CI],
0.38-1.29; P=0.26) or 30-day mortality (relative risk, 0.58; 95% CI, 0.20-1.64;
P=0.30). There were no significant differences in new-single, multiple, or total
number of lesions. The use of EPD was associated with a significantly smaller
ischemic volume per lesion (standardized mean difference, -0.52; 95% CI, -0.85 to
-0.20; P=0.002) and smaller total volume of lesions (standardized mean
difference, -0.23; 95% CI, -0.42 to -0.03; P=0.02). Subgroup analysis by type of
valve showed an overall trend toward significant reduction in new lesions per
patient using EPD (standardized mean difference, -0.41; 95% CI, -0.82 to 0.00;
P=0.05), driven by self-expanding devices. CONCLUSIONS: The use of EPD during
TAVI may be associated with smaller volume of silent ischemic lesions and smaller
total volume of silent ischemic lesions. However, EPD may not reduce the number
of new-single, multiple, or total number of lesions. There was only very low
quality of evidence showing no significant differences between patients
undergoing TAVI with or without EPD with respect to clinically evident stroke and
mortality.
PMID- 28411260
TI - The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With
Stroke.
AB - BACKGROUND AND PURPOSE: The Emergency Medical Services field triage to stroke
centers has gained considerable complexity with the recent demonstration of
clinical benefit of endovascular treatment for acute ischemic stroke. We sought
to describe a new smartphone freeware application designed to assist Emergency
Medical Services professionals with the field assessment and destination triage
of patients with acute ischemic stroke. METHODS: Review of the application's
platform and its development as well as the different variables, assessments,
algorithms, and assumptions involved. RESULTS: The FAST-ED (Field Assessment
Stroke Triage for Emergency Destination) application is based on a built-in
automated decision-making algorithm that relies on (1) a brief series of
questions assessing patient's age, anticoagulant usage, time last known normal,
motor weakness, gaze deviation, aphasia, and hemineglect; (2) a database of all
regional stroke centers according to their capability to provide endovascular
treatment; and (3) Global Positioning System technology with real-time traffic
information to compute the patient's eligibility for intravenous tissue-type
plasminogen activator or endovascular treatment as well as the
distances/transportation times to the different neighboring stroke centers in
order to assist Emergency Medical Services professionals with the decision about
the most suitable destination for any given patient with acute ischemic stroke.
CONCLUSIONS: The FAST-ED smartphone application has great potential to improve
the triage of patients with acute ischemic stroke, as it seems capable to
optimize resources, reduce hospital arrivals times, and maximize the use of both
intravenous tissue-type plasminogen activator and endovascular treatment
ultimately leading to better clinical outcomes. Future field studies are needed
to properly evaluate the impact of this tool in stroke outcomes and resource
utilization.
PMID- 28411261
TI - Feasibility and Diagnostic Value of Cardiovascular Magnetic Resonance Imaging
After Acute Ischemic Stroke of Undetermined Origin.
AB - BACKGROUND AND PURPOSE: Etiology of acute ischemic stroke remains undetermined
(cryptogenic) in about 25% of patients after state-of-the-art diagnostic work-up.
METHODS: One-hundred and three patients with magnetic resonance imaging (MRI)
proven acute ischemic stroke of undetermined origin were prospectively enrolled
and underwent 3-T cardiac MRI and magnetic resonance angiography of the aortic
arch in addition to state-of-the-art diagnostic work-up, including
transesophageal echocardiography (TEE). We analyzed the feasibility, diagnostic
accuracy, and added value of cardiovascular MRI (cvMRI) compared with TEE for
detecting sources of stroke. RESULTS: Overall, 102 (99.0%) ischemic stroke
patients (median 63 years [interquartile range, 53-72], 24% female, median NIHSS
(National Institutes of Health Stroke Scale) score on admission 2 [interquartile
range, 1-4]) underwent cvMRI and TEE in hospital; 89 (86.4%) patients completed
the cvMRI examination. In 93 cryptogenic stroke patients, a high-risk embolic
source was found in 9 (8.7%) patients by cvMRI and in 11 (11.8%) patients by
echocardiography, respectively. cvMRI and echocardiography findings were
consistent in 80 (86.0%) patients, resulting in a degree of agreement of
kappa=0.24. In 82 patients with cryptogenic stroke according to routine work-up,
including TEE, cvMRI identified stroke etiology in additional 5 (6.1%) patients.
Late gadolinium enhancement consistent with previous myocardial infarction was
found in 13 (14.6%) out of 89 stroke patients completing cvMRI. Only 2 of these
13 patients had known coronary artery disease. CONCLUSIONS: Our study
demonstrated that cvMRI was feasible in the vast majority of included patients
with acute ischemic stroke. The diagnostic information of cvMRI seems to be
complementary to TEE but is not replacing echocardiography after acute ischemic
stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT01917955.
PMID- 28411262
TI - Aspirin's Benefits Were Previously Underestimated and Are Primarily Accrued in
the Acute Setting.
PMID- 28411263
TI - Use of Platelet Function Testing Before Pipeline Embolization Device Placement: A
Multicenter Cohort Study.
AB - BACKGROUND AND PURPOSE: Thromboembolic complications constitute a significant
source of morbidity after neurointerventional procedures. Flow diversion using
the pipeline embolization device for the treatment of intracranial aneurysms
necessitates the use of dual antiplatelet therapy to reduce this risk. The use of
platelet function testing before pipeline embolization device placement remains
controversial. METHODS: A retrospective review of prospectively maintained
databases at 3 academic institutions was performed from the years 2009 to 2016 to
identify patients with intracranial aneurysms treated with pipeline embolization
device placement. Clinical and radiographic data were analyzed with emphasis on
thromboembolic complications and clopidogrel responsiveness. RESULTS: A total of
402 patients underwent 414 pipeline embolization device procedures for the
treatment of 465 intracranial aneurysms. Thromboembolic complications were
encountered in 9.2% of procedures and were symptomatic in 5.6%. Clopidogrel
nonresponders experienced a significantly higher rate of thromboembolic
complications compared with clopidogrel responders (17.4% versus 5.6%). This risk
was significantly lower in nonresponders who were switched to ticagrelor when
compared with patients who remained on clopidogrel (2.7% versus 24.4%). In
patients who remained on clopidogrel, the rate of thromboembolic complications
was significantly lower in those who received a clopidogrel boost within 24 hours
pre-procedure when compared with those who did not (9.8% versus 51.9%). There was
no significant difference in the rate of hemorrhagic complications between
groups. CONCLUSIONS: Clopidogrel nonresponders experienced a significantly higher
rate of thromboembolic complications when compared with clopidogrel responders.
However, this risk seems to be mitigated in nonresponders who were switched to
ticagrelor or received a clopidogrel boost within 24 hours pre-procedure.
PMID- 28411266
TI - Genetic Variation at the Sulfonylurea Receptor, Type 2 Diabetes, and Coronary
Heart Disease.
AB - Despite widespread clinical use in the treatment of type 2 diabetes, the impact
of sulfonylurea therapy on cardiovascular outcomes remains uncertain. Studies of
naturally occurring genetic variation can be used to anticipate the expected
clinical consequences of a pharmacological therapy. A common missense variant in
the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S)
promotes closure of the target channel of sulfonylurea therapy and is associated
with increased insulin secretion, thus mimicking the effects of sulfonylurea
therapy. Using individual-level data from 120,286 participants in the UK Biobank
and summary association results from four large-scale genome-wide association
studies, we examined the impact of this variant on cardiometabolic traits, type 2
diabetes, and coronary heart disease. The p.A1369S variant was associated with a
significantly lower risk of type 2 diabetes (odds ratio [OR] 0.93; 95% CI 0.91,
0.95; P = 1.2 * 10-11). The variant was associated with increased BMI (+0.062
kg/m2; 95% CI 0.037, 0.086; P = 8.1 * 10-7) but lower waist-to-hip ratio adjusted
for BMI, a marker of abdominal fat distribution. Furthermore, p.A1369S was
associated with a reduced risk of coronary heart disease (OR 0.98; 95% CI 0.96,
0.99; P = 5.9 * 10-4). These results suggest that, despite a known association
with increased weight, long-term sulfonylurea therapy may reduce the risk of
coronary heart disease.
PMID- 28411264
TI - GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to
Predict the Vascular Recurrence After Stroke.
AB - BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the
first year after ischemic stroke (IS) or transient ischemic attack. Clinical
scores do not predict the whole vascular recurrence risk; therefore, we aimed to
find genetic variants associated with recurrence that might improve the clinical
predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115
candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic
attack patients. The discovery cohort was prospectively recruited and included
1494 patients, 6.2% of them developed a new IS during the first year of follow
up. Replication analysis was performed in 2988 patients using SNPlex or
HumanOmni1-Quad technology. We generated a predictive model using Cox regression
(GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups
using a classification tree method. RESULTS: The analyses revealed that rs1800801
in the MGP gene (hazard ratio, 1.33; P=9*10-03), a gene related to artery
calcification, was associated with new IS during the first year of follow-up.
This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was
not significantly associated in a North American cohort (n=1.683). The GRECOS
score predicted new IS (P=3.2*10-09) and could classify patients, from low risk
of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of
genetic risk factors to the GRECOS score improves the prediction compared with
previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of
genetics could be useful to estimate vascular recurrence risk after IS. Genetic
variability in the MGP gene was associated with vascular recurrence in the
Spanish population.
PMID- 28411267
TI - NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by
Repressing the Hepatic FAM3A-ATP-Akt Pathway.
AB - Hepatic FAM3A expression is repressed under obese conditions, but the underlying
mechanism remains unknown. This study determined the role and mechanism of miR
423-5p in hepatic glucose and lipid metabolism by repressing FAM3A expression.
miR-423-5p expression was increased in the livers of obese diabetic mice and in
patients with nonalcoholic fatty liver disease (NAFLD) with decreased FAM3A
expression. miR-423-5p directly targeted FAM3A mRNA to repress its expression and
the FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic miR-423-5p inhibition
suppressed gluconeogenesis and improved insulin resistance, hyperglycemia, and
fatty liver in obese diabetic mice. In contrast, hepatic miR-423-5p
overexpression promoted gluconeogenesis and hyperglycemia and increased lipid
deposition in normal mice. miR-423-5p inhibition activated the FAM3A-ATP-Akt
pathway and repressed gluconeogenic and lipogenic gene expression in diabetic
mouse livers. The miR-423 precursor gene was further shown to be a target gene of
NFE2, which induced miR-423-5p expression to repress the FAM3A-ATP-Akt pathway in
cultured hepatocytes. Hepatic NFE2 overexpression upregulated miR-423-5p to
repress the FAM3A-ATP-Akt pathway, promoting gluconeogenesis and lipid deposition
and causing hyperglycemia in normal mice. In conclusion, under the obese
condition, activation of the hepatic NFE2/miR-423-5p axis plays important roles
in the progression of type 2 diabetes and NAFLD by repressing the FAM3A-ATP-Akt
signaling pathway.
PMID- 28411268
TI - Attention to Multiple Objects Facilitates Their Integration in Prefrontal and
Parietal Cortex.
AB - Selective attention is known to interact with perceptual organization. In visual
scenes, individual objects that are distinct and discriminable may occur on their
own, or in groups such as a stack of books. The main objective of this study is
to probe the neural interaction that occurs between individual objects when
attention is directed toward one or more objects. Here we record steady-state
visual evoked potentials via electrocorticography to directly assess the
responses to individual stimuli and to their interaction. When human participants
attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective
enhancement of only the neural interaction between stimuli, but not the responses
to individual stimuli. When only one stimulus is attended, the neural response to
that stimulus is selectively enhanced in prefrontal and parietal cortex. In
contrast, early visual areas generally manifest responses to individual stimuli
and to their interaction regardless of attentional task, although a subset of the
responses is modulated similarly to prefrontal and parietal cortex. Thus, the
neural representation of the visual scene as one progresses up the cortical
hierarchy becomes more highly task-specific and represents either individual
stimuli or their interaction, depending on the behavioral goal. Attention to
multiple objects facilitates an integration of objects akin to perceptual
grouping.SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as
distinct entities or as parts of a whole. Here we examine how attention to
multiple objects affects their neural representation. Previous studies measured
single-cell or fMRI responses and obtained only aggregate measures that combined
the activity to individual stimuli as well as their potential interaction. Here,
we directly measure electrocorticographic steady-state responses corresponding to
individual objects and to their interaction using a frequency-tagging technique.
Attention to two stimuli increases the interaction component that is a hallmark
for perceptual integration of stimuli. Furthermore, this stimulus-specific
interaction is represented in prefrontal and parietal cortex in a task-dependent
manner.
PMID- 28411270
TI - Short-Term Facilitation at a Detonator Synapse Requires the Distinct Contribution
of Multiple Types of Voltage-Gated Calcium Channels.
AB - Neuronal calcium elevations are shaped by several key parameters, including the
properties, density, and the spatial location of voltage-gated calcium channels
(VGCCs). These features allow presynaptic terminals to translate complex firing
frequencies and tune the amount of neurotransmitter released. Although
synchronous neurotransmitter release relies on both P/Q- and N-type VGCCs at
hippocampal mossy fiber-CA3 synapses, the specific contribution of VGCCs to
calcium dynamics, neurotransmitter release, and short-term facilitation remains
unknown. Here, we used random-access two-photon calcium imaging together with
electrophysiology in acute mouse hippocampal slices to dissect the roles of P/Q-
and N-type VGCCs. Our results show that N-type VGCCs control glutamate release at
a limited number of release sites through highly localized Ca2+ elevations and
support short-term facilitation by enhancing multivesicular release. In contrast,
Ca2+ entry via P/Q-type VGCCs promotes the recruitment of additional release
sites through spatially homogeneous Ca2+ elevations. Altogether, our results
highlight the specialized contribution of P/Q- and N-types VGCCs to
neurotransmitter release.SIGNIFICANCE STATEMENT In presynaptic terminals,
neurotransmitter release is dynamically regulated by the transient opening of
different types of voltage-gated calcium channels. Hippocampal giant mossy fiber
terminals display extensive short-term facilitation during repetitive activity,
with a large several fold postsynaptic response increase. Though, how giant mossy
fiber terminals leverage distinct types of voltage-gated calcium channels to
mediate short-term facilitation remains unexplored. Here, we find that P/Q- and N
type VGCCs generate different spatial patterns of calcium elevations in giant
mossy fiber terminals and support short-term facilitation through specific
participation in two mechanisms. Whereas N-type VGCCs contribute only to the
synchronization of multivesicular release, P/Q-type VGCCs act through microdomain
signaling to recruit additional release sites.
PMID- 28411269
TI - Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for
Visual Pathway Development.
AB - What pathways specify retinal ganglion cell (RGC) fate in the developing retina?
Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is
required for RGC differentiation and for optic nerve formation in mice in vivo,
and is sufficient to differentiate human induced pluripotent stem cells into
electrophysiologically active RGCs. These data place Sox4 downstream of RE1
silencing transcription factor in regulating RGC fate, and further describe a
newly identified, Sox4-regulated site for post-translational modification with
small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's
nuclear localization and its ability to promote RGC differentiation, providing a
mechanism for the SoxC familial compensation observed here and elsewhere in the
nervous system. These data define novel regulatory mechanisms for this SoxC
molecular network, and suggest pro-RGC molecular approaches for cell replacement
based therapies for glaucoma and other optic neuropathies.SIGNIFICANCE STATEMENT
Glaucoma is the most common cause of blindness worldwide and, along with other
optic neuropathies, is characterized by loss of retinal ganglion cells (RGCs).
Unfortunately, vision and RGC loss are irreversible, and lead to bilateral
blindness in ~14% of all diagnosed patients. Differentiated and transplanted RGC
like cells derived from stem cells have the potential to replace neurons that
have already been lost and thereby to restore visual function. These data uncover
new mechanisms of retinal progenitor cell (RPC)-to-RGC and human stem cell-to-RGC
fate specification, and take a significant step toward understanding neuronal and
retinal development and ultimately cell-transplant therapy.
PMID- 28411271
TI - Neural Correlates of Semantic Prediction and Resolution in Sentence Processing.
AB - Most brain-imaging studies of language comprehension focus on activity following
meaningful stimuli. Testing adult human participants with high-density EEG, we
show that, already before the presentation of a critical word, context-induced
semantic predictions are reflected by a neurophysiological index, which we
therefore call the semantic readiness potential (SRP). The SRP precedes critical
words if a previous sentence context constrains the upcoming semantic content
(high-constraint contexts), but not in unpredictable (low-constraint) contexts.
Specific semantic predictions were indexed by SRP sources within the motor system
in dorsolateral hand motor areas for expected hand-related words (e.g., "write"),
but in ventral motor cortex for face-related words ("talk"). Compared with
affirmative sentences, negated ones led to medial prefrontal and more widespread
motor source activation, the latter being consistent with predictive semantic
computation of alternatives to the negated expected concept. Predictive
processing of semantic alternatives in negated sentences is further supported by
a negative-going event-related potential at ~400 ms (N400), which showed the
typical enhancement to semantically incongruent sentence endings only in high
constraint affirmative contexts, but not to high-constraint negated ones. These
brain dynamics reveal the interplay between semantic prediction and resolution
(match vs error) processing in sentence understanding.SIGNIFICANCE STATEMENT Most
neuroscientists agree on the eminent importance of predictive mechanisms for
understanding basic as well as higher brain functions. This contrasts with a
sparseness of brain measures that directly reflects specific aspects of
prediction, as they are relevant in the processing of language and thought. Here
we show that when critical words are strongly expected in their sentence context,
a predictive brain response reflects meaning features of these anticipated
symbols already before they appear. The granularity of the semantic predictions
was so fine grained that the cortical sources in sensorimotor and medial
prefrontal cortex even distinguished between predicted face- or hand-related
action words (e.g., the words "lick" or "pick") and between affirmative and
negated sentence meanings.
PMID- 28411272
TI - Disconnection of the Perirhinal and Postrhinal Cortices Impairs Recognition of
Objects in Context But Not Contextual Fear Conditioning.
AB - The perirhinal cortex (PER) is known to process object information, whereas the
rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in
primates, is thought to process spatial information. A number of studies,
however, provide evidence that both areas are involved in processing contextual
information. In this study, we tested the hypothesis that the rat POR relies on
object information received from the PER to form complex representations of
context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and
renewal) and two context-guided object recognition tasks (with 3D and 2D
objects), we examined the effects of crossed excitotoxic lesions to the POR and
the contralateral PER. Performance of rats with crossed lesions was compared with
that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We
found that rats with contralateral PER-POR lesions were impaired in object
context recognition but not in contextual FC. Therefore, interaction between the
POR and PER is necessary for context-guided exploratory behavior but not for
associating fear with context. Our results provide evidence for the hypothesis
that the POR relies on object and pattern information from the PER to encode
representations of context. The association of fear with a context, however, may
be supported by alternate cortical and/or subcortical pathways when PER-POR
interaction is not available. Our results suggest that contextual FC may
represent a special case of context-guided behavior.SIGNIFICANCE STATEMENT
Representations of context are important for perception, memory, decision making,
and other cognitive processes. Moreover, there is extensive evidence that the use
of contextual representations to guide appropriate behavior is disrupted in
neuropsychiatric and neurological disorders including developmental disorders,
schizophrenia, affective disorders, and Alzheimer's disease. Many of these
disorders are accompanied by changes in parahippocampal and hippocampal
structures. Understanding how context is represented in the brain and how
parahippocampal structures are involved will enhance our understanding and
treatment of the cognitive and behavioral symptoms associated with neurological
disorders and neuropsychiatric disease.
PMID- 28411273
TI - Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory
Stimuli.
AB - Many environmental stimuli contain temporal regularities, a feature that can help
predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency
neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism
for enhancing neuronal responses and perceptual sensitivity, by aligning high
excitability phases to events within a stimulus stream. Previous experiments show
that rhythmic structure has a behavioral benefit even when the rhythm itself is
below perceptual detection thresholds (ten Oever et al., 2014). It is not known
whether this "inaudible" rhythmic sound stream also induces entrainment. Here we
tested this hypothesis using magnetoencephalography and electrocorticography in
humans to record changes in neuronal activity as subthreshold rhythmic stimuli
gradually became audible. We found that significant phase locking to the rhythmic
sounds preceded participants' detection of them. Moreover, no significant
auditory-evoked responses accompanied this prethreshold entrainment. These
auditory-evoked responses, distinguished by robust, broad-band increases in
intertrial coherence, only appeared after sounds were reported as audible. Taken
together with the reduced perceptual thresholds observed for rhythmic sequences,
these findings support the proposition that entrainment of low-frequency
oscillations serves a mechanistic role in enhancing perceptual sensitivity for
temporally predictive sounds. This framework has broad implications for
understanding the neural mechanisms involved in generating temporal predictions
and their relevance for perception, attention, and awareness.SIGNIFICANCE
STATEMENT The environment is full of rhythmically structured signals that the
nervous system can exploit for information processing. Thus, it is important to
understand how the brain processes such temporally structured, regular features
of external stimuli. Here we report the alignment of slowly fluctuating
oscillatory brain activity to external rhythmic structure before its behavioral
detection. These results indicate that phase alignment is a general mechanism of
the brain to process rhythmic structure and can occur without the perceptual
detection of this temporal structure.
PMID- 28411274
TI - Posterior Orbitofrontal and Anterior Cingulate Pathways to the Amygdala Target
Inhibitory and Excitatory Systems with Opposite Functions.
AB - The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC)
with the amygdala is essential in cognitive-emotional functions. The pOFC also
sends a uniquely one-way excitatory pathway to the amygdalar inhibitory
intercalated masses (IM), which inhibit the medial part of the central amygdalar
nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar
activation of autonomic structures and emotional arousal. Using multiple labeling
approaches to identify pathways and their postsynaptic sites in the amygdala in
rhesus monkeys, we found that the anterior cingulate cortex innervated mostly the
basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic
arousal. By contrast, a pathway from pOFC to IM exceeded all other pathways to
the amygdala by density and size and proportion of large and efficient terminals.
Moreover, whereas pOFC terminals in IM innervated each of the three distinct
classes of inhibitory neurons, most targeted neurons expressing dopamine- and
cAMP-regulated phosphoprotein (DARPP-32+), known to be modulated by dopamine. The
predominant pOFC innervation of DARPP-32+ neurons suggests activation of IM and
inhibition of CeM, resulting in modulated autonomic function. By contrast,
inhibition of DARPP-32 neurons in IM by high dopamine levels disinhibits CeM and
triggers autonomic arousal. The findings provide a mechanism to help explain how
a strong pOFC pathway, which is poised to moderate activity of CeM, through IM,
can be undermined by the high level of dopamine during stress, resulting in
collapse of potent inhibitory mechanisms in the amygdala and heightened autonomic
drive, as seen in chronic anxiety disorders.SIGNIFICANCE STATEMENT The dialogue
between prefrontal cortex and amygdala allows thoughts and emotions to influence
actions. The posterior orbitofrontal cortex sends a powerful pathway that targets
a special class of amygdalar intercalated mass (IM) inhibitory neurons, whose
wiring may help modulate autonomic function. By contrast, the anterior cingulate
cortex innervates other amygdalar parts, activating circuits to help avoid
danger. Most IM neurons in primates label for the protein DARPP-32, known to be
activated or inhibited based on the level of dopamine. Stress markedly increases
dopamine release and inhibits IM neurons, compromises prefrontal control of the
amygdala, and sets off a general alarm system as seen in affective disorders,
such as chronic anxiety and post-traumatic stress disorder.
PMID- 28411275
TI - Odorant Sensory Input Modulates DNA Secondary Structure Formation and
Heterogeneous Ribonucleoprotein Recruitment on the Tyrosine Hydroxylase and
Glutamic Acid Decarboxylase 1 Promoters in the Olfactory Bulb.
AB - Adaptation of neural circuits to changes in sensory input can modify several
cellular processes within neurons, including neurotransmitter biosynthesis
levels. For a subset of olfactory bulb interneurons, activity-dependent changes
in GABA are reflected by corresponding changes in Glutamate decarboxylase 1
(Gad1) expression levels. Mechanisms regulating Gad1 promoter activity are poorly
understood, but here we show that a conserved G:C-rich region in the mouse Gad1
proximal promoter region both recruits heterogeneous nuclear ribonucleoproteins
(hnRNPs) that facilitate transcription and forms single-stranded DNA secondary
structures associated with transcriptional repression. This promoter architecture
and function is shared with Tyrosine hydroxylase (Th), which is also modulated by
odorant-dependent activity in the olfactory bulb. This study shows that the
balance between DNA secondary structure formation and hnRNP binding on the mouse
Th and Gad1 promoters in the olfactory bulb is responsive to changes in odorant
dependent sensory input. These findings reveal that Th and Gad1 share a novel
transcription regulatory mechanism that facilitates sensory input-dependent
regulation of dopamine and GABA expression.SIGNIFICANCE STATEMENT Adaptation of
neural circuits to changes in sensory input can modify several cellular processes
within neurons, including neurotransmitter biosynthesis levels. This study shows
that transcription of genes encoding rate-limiting enzymes for GABA and dopamine
biosynthesis (Gad1 and Th, respectively) in the mammalian olfactory bulb is
regulated by G:C-rich regions that both recruit heterogeneous nuclear
ribonucleoproteins (hnRNPs) to facilitate transcription and form single-stranded
DNA secondary structures associated with repression. hnRNP binding and formation
of DNA secondary structure on the Th and Gad1 promoters are mutually exclusive,
and odorant sensory input levels regulate the balance between these regulatory
features. These findings reveal that Th and Gad1 share a transcription regulatory
mechanism that facilitates odorant-dependent regulation of dopamine and GABA
expression levels.
PMID- 28411278
TI - Correction: Inhibition of SOAT1 Suppresses Glioblastoma Growth via Blocking SREBP
1-Mediated Lipogenesis.
PMID- 28411277
TI - Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted
Vaccination.
AB - Purpose: Patients with glioblastoma have less than 15-month median survival
despite surgical resection, high-dose radiation, and chemotherapy with
temozolomide. We previously demonstrated that targeting cytomegalovirus pp65
using dendritic cells (DC) can extend survival and, in a separate study, that
dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony
stimulating factor (GM-CSF) potentiate tumor-specific immune responses in
patients with glioblastoma. Here, we evaluated pp65-specific cellular responses
following DI-TMZ with pp65-DCs and determined the effects on long-term
progression-free survival (PFS) and overall survival (OS).Experimental Design:
Following standard-of-care, 11 patients with newly diagnosed glioblastoma
received DI-TMZ (100 mg/m2/d * 21 days per cycle) with at least three vaccines of
pp65 lysosome-associated membrane glycoprotein mRNA-pulsed DCs admixed with GM
CSF on day 23 +/- 1 of each cycle. Thereafter, monthly DI-TMZ cycles and pp65-DCs
were continued if patients had not progressed.Results: Following DI-TMZ cycle 1
and three doses of pp65-DCs, pp65 cellular responses significantly increased.
After DI-TMZ, both the proportion and proliferation of regulatory T cells (Tregs)
increased and remained elevated with serial DI-TMZ cycles. Median PFS and OS were
25.3 months [95% confidence interval (CI), 11.0-infinity] and 41.1 months (95%
CI, 21.6-infinity), exceeding survival using recursive partitioning analysis and
matched historical controls. Four patients remained progression-free at 59 to 64
months from diagnosis. No known prognostic factors [age, Karnofsky performance
status (KPS), IDH-1/2 mutation, and MGMT promoter methylation] predicted more
favorable outcomes for the patients in this cohort.Conclusions: Despite increased
Treg proportions following DI-TMZ, patients receiving pp65-DCs showed long-term
PFS and OS, confirming prior studies targeting cytomegalovirus in glioblastoma.
Clin Cancer Res; 23(8); 1898-909. (c)2017 AACR.
PMID- 28411280
TI - Interrelationships between Infliximab and Recombinant Tumor Necrosis Factor-alpha
in Plasma Using Minimal Physiologically Based Pharmacokinetic Models.
AB - The soluble cytokine tumor necrosis factor-alpha (TNF-alpha) is an important
target for many therapeutic proteins used in the treatment of rheumatoid
arthritis. Biologics targeting TNF-alpha exert their pharmacologic effects
through binding and neutralizing this cytokine and preventing it from binding to
its cell surface receptors. The magnitude of their pharmacologic effects directly
corresponds to the extent and duration of free TNF-alpha suppression. However,
endogenous TNF-alpha is of low abundance, so it is quite challenging to assess
the free TNF-alpha suppression experimentally. Here we have applied an
experimental approach to bypass this difficulty by giving recombinant human TNF
alpha (rhTNF-alpha) to rats by s.c. infusion. This boosted TNF-alpha
concentration enabled quantification of TNF-alpha in plasma. Free rhTNF-alpha
concentrations were measured after separation from the infliximab-rhTNF-alpha
complex using Dynabeads Protein A. The interrelationship of infliximab and TNF
alpha was assessed with minimal physiologically based pharmacokinetic models for
TNF-alpha and infliximab with a target-mediated drug disposition component.
Knowledge of TNF-alpha pharmacokinetics allows reliable prediction of the free
TNF-alpha suppression with either free or total TNF-alpha concentration profiles.
The experimental and modeling approaches in our study may aid in the development
of next-generation TNF-alpha inhibitors with improved therapeutic effects.
PMID- 28411279
TI - Characterization and Interspecies Scaling of rhTNF-alpha Pharmacokinetics with
Minimal Physiologically Based Pharmacokinetic Models.
AB - Tumor necrosis factor-alpha (TNF-alpha) is a soluble cytokine and target of
specific monoclonal antibodies (mAbs) and other biologic agents used in the
treatment of inflammatory diseases. These biologics exert their pharmacological
effects through binding and neutralizing TNF-alpha, and thus they prevent TNF
alpha from interacting with its cell surface receptors. The magnitude of the
pharmacological effects is governed not only by the pharmacokinetics (PK) of
mAbs, but also by the kinetic fate of TNF-alpha We have examined the
pharmacokinetics of recombinant human TNF-alpha (rhTNF-alpha) in rats at low
doses and quantitatively characterized its pharmacokinetic features with a
minimal physiologically based pharmacokinetic model. Our experimental and
literature-digitalized PK data of rhTNF-alpha in rats across a wide range of
doses were applied to global model fitting. rhTNF-alpha exhibits permeability
rate-limited tissue distribution and its elimination is comprised of a saturable
clearance pathway mediated by tumor necrosis factor receptor binding and
disposition and renal filtration. The resulting model integrated with classic
allometry was further used for interspecies PK scaling and resulted in model
predictions that agreed well with experimental measurements in monkeys. In
addition, a semimechanistic model was proposed and applied to explore the
absorption kinetics of rhTNF-alpha following s.c. and other routes of
administration. The model suggests substantial presystemic degradation of rhTNF
alpha for s.c. and i.m. routes and considerable lymph uptake contributing to the
overall systemic absorption through the stomach wall and gastrointestinal wall
routes of dosing. This report provides comprehensive modeling and key insights
into the complexities of absorption and disposition of a major cytokine.
PMID- 28411281
TI - Long-Term Stability of Cryopreserved Human Hepatocytes: Evaluation of Phase I and
II Drug-Metabolizing Enzyme Activities and CYP3A4/5 Induction for More than a
Decade.
AB - We evaluated the long-term stability of hepatocytes stored in the vapor phase of
liquid nitrogen for their viability, cytochrome P450 (CYP) 1A2 activity, CYP3A4/5
activity, uridine diphosphate-glucuronosyl transferase (UGT) activity,
sulfotransferase (SULT) activity, and CYP3A4/5 induction during 14 years of
preservation. No substantial degradation of viability, CYP1A2 activity, UGT
activity, or CYP3A4/5 induction was observed. CYP3A4/5 activity showed a slight
decrease after 7 years of storage, and SULT activity gradually decreased during
storage, although substantial activities remained even after 14 years. These
results indicate that cryopreserved human hepatocytes can be stored stably for
more than a decade with little or no change in viability, activity of drug
metabolizing enzymes, or CYP3A4/5 induction, and can be widely applicable to
qualitative research in drug metabolism.
PMID- 28411282
TI - Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a
Children's Oncology Group report.
AB - Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal
instability. Approximately 50% of patients have disease relapse, and novel
prognostic markers are needed to improve risk stratification. We performed genome
wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's
Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and
Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs)
and determine their associations with treatment outcome. Data from Affymetrix and
Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average
of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring
altered genomic regions were identified, and the presence of CNAs was found to be
associated with decreased 3-year overall survival (OS), event-free survival
(EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95%
confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI,
1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS
in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI,
1.1-2.6, respectively). Additional studies are required to test the prognostic
significance of CNA presence in disease relapse in patients with AML. COG studies
AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials.gov as
#NCT01407757, #NCT00070174, and #NCT00003790, respectively.
PMID- 28411283
TI - Systematic functional perturbations uncover a prognostic genetic network driving
human breast cancer.
AB - Prognostic classifiers conceivably comprise biomarker genes that functionally
contribute to the oncogenic and metastatic properties of cancer, but this has not
been investigated systematically. The transcription factor Fra-1 not only has an
essential role in breast cancer, but also drives the expression of a highly
prognostic gene set. Here, we systematically perturbed the function of 31
individual Fra-1-dependent poor-prognosis genes and examined their impact on
breast cancer growth in vivo. We find that stable shRNA depletion of each of nine
individual signature genes strongly inhibits breast cancer growth and
aggressiveness. Several factors within this nine-gene set regulate each other's
expression, suggesting that together they form a network. The nine-gene set is
regulated by estrogen, ERBB2 and EGF signaling, all established breast cancer
factors. We also uncover three transcription factors, MYC, E2F1 and TP53, which
act alongside Fra-1 at the core of this network. ChIP-Seq analysis reveals that a
substantial number of genes are bound, and regulated, by all four transcription
factors. The nine-gene set retains significant prognostic power and includes
several potential therapeutic targets, including the bifunctional enzyme PAICS,
which catalyzes purine biosynthesis. Depletion of PAICS largely cancelled breast
cancer expansion, exemplifying a prognostic gene with breast cancer activity. Our
data uncover a core genetic and prognostic network driving human breast cancer.
We propose that pharmacological inhibition of components within this network,
such as PAICS, may be used in conjunction with the Fra-1 prognostic classifier
towards personalized management of poor prognosis breast cancer.
PMID- 28411284
TI - Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new
therapeutic targets in breast cancer.
AB - Here, we identified two new molecular targets, which are functionally sufficient
to metabolically confer the tamoxifen-resistance phenotype in human breast cancer
cells. Briefly, ~20 proteins were first selected as potential candidates, based
on unbiased proteomics analysis, using tamoxifen-resistant cell lines. Then, the
cDNAs of the most promising candidates were systematically transduced into MCF-7
cells. Remarkably, NQO1 and GCLC were both functionally sufficient to
autonomously confer a tamoxifen-resistant metabolic phenotype, characterized by
i) increased mitochondrial biogenesis, ii) increased ATP production and iii)
reduced glutathione levels. Thus, we speculate that pharmacological inhibition of
NQO1 and GCLC may be new therapeutic strategies for overcoming tamoxifen
resistance in breast cancer patients. In direct support of this notion, we
demonstrate that treatment with a known NQO1 inhibitor (dicoumarol) is indeed
sufficient to revert the tamoxifen-resistance phenotype. As such, these findings
could have important translational significance for the prevention of tumor
recurrence in ER(+) breast cancers, which is due to an endocrine resistance
phenotype. Importantly, we also show here that NQO1 has significant prognostic
value as a biomarker for the prediction of tumor recurrence. More specifically,
higher levels of NQO1 mRNA strongly predict patient relapse in high-risk ER(+)
breast cancer patients receiving endocrine therapy (mostly tamoxifen; H.R. >
2.15; p = 0.007).
PMID- 28411285
TI - Monitoring of Hypercoagulability by Thromboelastography in Bariatric Surgery.
AB - BACKGROUND Obesity is known as a major risk factor for postoperative vein
thrombosis. Thromboelastography (TEG) is used to monitor viscoelastic features of
blood clots. The aim of this study was to determine hypercoagulable states in
patients undergoing bariatric surgery and to assess dynamics of coagulation
parameters in the perioperative setting using TEG. MATERIAL AND METHODS We
included 60 consecutive patients undergoing bariatric surgery. TEG alterations
were assessed at 4 time points: at baseline, after the surgery, and on
postoperative day 1 (POD1) and 2 (POD2). Hypercoagulable state was defined when
patients showed clot strength (G) of >=11 dynes/cm2 or maximum amplitude (MA)
>=68 mm. RESULTS Fourteen patients (23.3%) out of 60 showed hypercoagulability
prior to surgery on TEG. Fibrinogen levels were significantly higher in the G
>=11 group compared to the G <11 group, at 4.2 and 3.8 g/l, respectively
(p=0.02). Seventeen patients (28.3%) had MA >=68 mm at baseline. Fibrinogen
levels increased significantly from 3.90 at baseline to 4.16 g/l in POD2
(p<0.001). There was an increase in mean reaction time from baseline (6.74 s) to
POD2 (7.43 s, p=0.022). We found a correlation between baseline fibrinogen levels
and MA (R=0.431, p=0.001) or G (R=0.387, p=0.003). ROC curve analysis showed that
fibrinogen levels can predict clot strength (G) >=11 dynes/cm2 with AUC=0.680
(p=0.044). CONCLUSIONS A considerable proportion of patients referred to
bariatric surgery show a trend towards hypercoagulability on TEG. This study
shows the potential of hypercoagulation monitoring by TEG in the perioperative
setting of bariatric surgery.
PMID- 28411287
TI - Impact of a Connected Care Model on 30-Day Readmission Rates from Skilled Nursing
Facilities.
AB - BACKGROUND: About one-fifth of hospitalized Medicare beneficiaries are discharged
to skilled nursing facilities (SNFs) for post-acute care. Readmissions are common
but interventions to reduce readmissions are scarce. OBJECTIVE: To assess the
impact of a connected care model on 30-day hospital readmission rates among
patients discharged to SNFs. DESIGN: Retrospective cohort. SETTING: SNFs that
receive referrals from an academic medical center in Cleveland, Ohio.
PARTICIPANTS: All patients admitted to Cleveland Clinic main campus between
January 1, 2011 and December 31, 2014 and subsequently discharged to 7
intervention SNFs or 103 control SNFs. INTERVENTIONS: Hospital-employed
physicians and advanced practice professionals (nurse practitioners and physician
assistants) visited SNF patients 4 to 5 times per week. RESULTS: During the study
period, 13,544 patients were discharged to SNFs within a 25-miles radius of
Cleveland Clinic main campus. Of these, 3334 were discharged to 7 intervention
SNFs and 10,201 were discharged to 103 usualcare SNFs. During the intervention
phase (2013-2014), adjusted 30-day readmission rates declined at the intervention
SNFs (28.1% to 21.7%, P < 0.001), while there was a slight increase at control
SNFs (27.1 % to 28.5%, P < 0.001). The absolute reductions ranged from 4.6% for
patients at low risk for readmission to 9.1% for patients at high risk, and
medical patients benefited more than surgical patients. CONCLUSIONS: A program of
frequent visits by hospital employed physicians and advanced practice
professionals at SNFs can reduce 30-day readmission rates. Journal of Hospital
Medicine 2017;12:238-244.
PMID- 28411286
TI - Rapid Induction Therapy with Oral Tacrolimus in Elderly Patients with Refractory
Ulcerative Colitis Can Easily Lead to Elevated Tacrolimus Concentrations in
Blood: A Report of 5 Cases.
AB - BACKGROUND Tacrolimus is reportedly effective for the treatment of refractory
ulcerative colitis (UC). At our hospital, there has been an increase in the
number of patients, including elderly patients, with refractory UC treated with
tacrolimus. Here, we review the data from 5 patients with elderly-onset UC
treated with tacrolimus as remission induction therapy. CASE REPORT The subjects
were 5 patients >=65 years of age with refractory UC who had received oral
tacrolimus as remission induction therapy between 2009 and 2014 (3 men and 2
women; median age at onset, 75 years). At the start of the tacrolimus treatment,
the median duration of disease was 3 months, and the type of UC was total colitis
in 4 cases, and left-sided colitis in 1 case. The drugs used concomitantly at the
start of tacrolimus treatment were mesalazine (5 cases) and an immunomodulator
drug (1 case). Standard induction therapy (0.05 mg/kg/day) was used in 2 patients
and rapid induction therapy (0.1 mg/kg/day) was used in the remaining 3 patients.
One week after the start of treatment, the blood trough concentrations of
tacrolimus were over the target level of 15 mg/mL in 4 patients. The clinical
activity index values on day 0 and day 14 were 10.6+/-2.1 and 7.6+/-3.4,
respectively. The ulcerative colitis endoscopic index of severity in the
remaining 3 patients, after excluding the 2 patients who required colectomy
within 14 days after the start of tacrolimus therapy, was 7.3+/-1.0 before the
start of the tacrolimus treatment, improving to 4.5+/-0.5 on day 14.
Subsequently, 1 of these 3 patients was also judged to need surgery due to
symptom exacerbation, while complete remission was maintained in the other 2
patients. CONCLUSIONS In elderly-onset refractory UC patients, tacrolimus appears
to be effective as remission induction therapy. However, since tacrolimus
concentrations in the blood can rise easily in elderly patients, frequent
monitoring of the drug concentrations and dosage adjustments are necessary.
PMID- 28411288
TI - Predicting 30-Day Pneumonia Readmissions Using Electronic Health Record Data.
AB - BACKGROUND: Readmissions after hospitalization for pneumonia are common, but the
few risk-prediction models have poor to modest predictive ability. Data routinely
collected in the electronic health record (EHR) may improve prediction.
OBJECTIVE: To develop pneumonia-specific readmission risk-prediction models using
EHR data from the first day and from the entire hospital stay ("full stay").
DESIGN: Observational cohort study using stepwise-backward selection and cross
validation. SUBJECTS: Consecutive pneumonia hospitalizations from 6 diverse
hospitals in north Texas from 2009-2010. MEASURES: All-cause nonelective 30-day
readmissions, ascertained from 75 regional hospitals. RESULTS: Of 1463 patients,
13.6% were readmitted. The first-day pneumonia-specific model included
sociodemographic factors, prior hospitalizations, thrombocytosis, and a modified
pneumonia severity index; the full-stay model included disposition status, vital
sign instabilities on discharge, and an updated pneumonia severity index
calculated using values from the day of discharge as additional predictors. The
full-stay pneumonia-specific model outperformed the first-day model (C statistic
0.731 vs 0.695; P = 0.02; net reclassification index = 0.08). Compared to a
validated multi-condition readmission model, the Centers for Medicare and
Medicaid Services pneumonia model, and 2 commonly used pneumonia severity of
illness scores, the full-stay pneumonia-specific model had better discrimination
(C statistic range 0.604-0.681; P < 0.01 for all comparisons), predicted a
broader range of risk, and better reclassified individuals by their true risk
(net reclassification index range, 0.09-0.18). CONCLUSIONS: EHR data collected
from the entire hospitalization can accurately predict readmission risk among
patients hospitalized for pneumonia. This approach outperforms a first-day
pneumonia-specific model, the Centers for Medicare and Medicaid Services
pneumonia model, and 2 commonly used pneumonia severity of illness scores.
Journal of Hospital Medicine 2017;12:209-216.
PMID- 28411289
TI - Evaluating Automated Rules for Rapid Response System Alarm Triggers in Medical
and Surgical Patients.
AB - BACKGROUND: The use of rapid response systems (RRS), which were designed to bring
clinicians with critical care expertise to the bedside to prevent unnecessary
deaths, has increased. RRS rely on accurate detection of acute deterioration
events. Early warning scores (EWS) have been used for this purpose but were
developed using heterogeneous populations. Predictive performance may differ in
medical vs surgical patients. OBJECTIVE: To evaluate the performance of published
EWS in medical vs surgical patient populations. DESIGN: Retrospective cohort
study. SETTING: Two tertiary care academic medical center hospitals in the
Midwest totaling more than 1500 beds. PATIENTS: All patients discharged from
January to December 2011. INTERVENTION: None. MEASUREMENTS: Time-stamped
longitudinal database of patient variables and outcomes, categorized as surgical
or medical. Outcomes included unscheduled transfers to the intensive care unit,
activation of the RRS, and calls for cardiorespiratory resuscitation
("resuscitation call"). The EWS were calculated and updated with every new
patient variable entry over time. Scores were considered accurate if they
predicted an outcome in the following 24 hours. RESULTS: All EWS demonstrated
higher performance within the medical population as compared to surgical: higher
positive predictive value (P < .0001 for all scores) and sensitivity (P < .0001
for all scores). All EWS had positive predictive values below 25%. CONCLUSIONS:
The overall poor performance of the evaluated EWS was marginally better in
medical patients when compared to surgical patients. Journal of Hospital Medicine
2017;12:217-223.
PMID- 28411290
TI - Prognosticating with the Hospitalized Patient 1-year Mortality Risk Score Using
Information Abstracted from the Medical Record.
AB - BACKGROUND: Predicting death risk in patients with diverse conditions is
difficult. The Hospitalized-patient One-year Mortality Risk (HOMR) score
accurately determines death risk in adults admitted to hospital using health
administrative data unavailable to clinicians and most researchers. OBJECTIVE:
Determine if HOMR is valid when calculated using data abstracted directly from
the medical record. DESIGN: Medical record review linked to population-based
administrative data. PARTICIPANTS: 4996 adults admitted in 2011 to a
nonpsychiatric service at a tertiary hospital. MAIN MEASURES: From the chart, we
abstracted information required to calculate the HOMR score and linked to
population-based mortality data to determine vital status within 1 year of
admission date. KEY RESULTS: Patients had a mean age of 55.6 (standard deviation
[SD], 20.7) with 563 (11.3%) dying. The mean chart HOMR score was 22 (SD, 12) and
significantly predicted death risk; a 1-point increase in HOMR increased death
odds by 19% (odds ratio, 1.192;, 95% confidence interval [CI], 1.175-1.210;, P <
0.0001). Chart HOMR was strongly discriminative ( C statistic 0.888) and well
calibrated (Hosmer-Lemeshow goodness-of-fit test, 12.9; P = 0.11). The observed
death risk was strongly associated with expected death risk (calibration slope,
1.02; 95% CI, 0.89-1.16). Notation of delirium or falls on admitting notes or
dependence for at least 1 activity of daily living were each associated with 1
year death risk independent of the HOMR score. CONCLUSIONS: One-year mortality
risk can be accurately determined in adults admitted to hospital with the HOMR
score calculated using information abstracted from the medical record. Patient
functional status was independently associated with death risk. Journal of
Hospital Medicine 2017;12:224-230.
PMID- 28411291
TI - Automating Venous Thromboembolism Risk Calculation Using Electronic Health Record
Data upon Hospital Admission: The Automated Padua Prediction Score.
AB - BACKGROUND: Venous thromboembolism (VTE) risk scores assist providers in
determining the relative benefit of prophylaxis for individual patients. While
automated risk calculation using simpler electronic health record (EHR) data is
feasible, it lacks clinical nuance and may be less predictive. Automated
calculation of the Padua Prediction Score (PPS), requiring more complex input
such as recent medical events and clinical status, may save providers time and
increase risk score use. OBJECTIVE: We developed the Automated Padua Prediction
Score (APPS) to auto-calculate a VTE risk score using EHR data drawn from prior
encounters and the first 4 hours of admission. We compared APPS to standard
practice of clinicians manually calculating the PPS to assess VTE risk. DESIGN:
Cohort study of 30,726 hospitalized patients. APPS was compared to manual
calculation of PPS by chart review from 300 randomly selected patients.
MEASUREMENTS: Prediction of hospital-acquired VTE not present on admission.
RESULTS: Compared to manual PPS calculation, no significant difference in average
score was found (5.5 vs. 5.1, P = 0.073), and area under curve (AUC) was similar
(0.79 vs. 0.76). Hospital- acquired VTE occurred in 260 (0.8%) of 30,726
patients. Those without VTE averaged APPS of 4.9 (standard deviation [SD], 2.6)
and those with VTE averaged 7.7 (SD, 2.6). APPS had AUC = 0.81 (confidence
interval [CI], 0.79-0.83) in patients receiving no pharmacologic prophylaxis and
AUC = 0.78 (CI, 0.76- 0.82) in patients receiving pharmacologic prophylaxis.
CONCLUSIONS: Automated calculation of VTE risk had similar ability to predict
hospital-acquired VTE as manual calculation despite differences in how often
specific scoring criteria were considered present by the 2 methods. Journal of
Hospital Medicine 2017;12: 231- 237.
PMID- 28411292
TI - Updating the Core Competencies in Hospital Medicine--2017 Revision: Introduction
and Methodology.
PMID- 28411293
TI - Safe and Effective Bedside Thoracentesis: A Review of the Evidence for Practicing
Clinicians.
AB - BACKGROUND: Physicians often care for patients with pleural effusion, a condition
that requires thoracentesis for evaluation and treatment. We aim to identify the
most recent advances related to safe and effective performance of thoracentesis.
METHODS: We performed a narrative review with a systematic search of the
literature. Two authors independently reviewed search results and selected
studies based on relevance to thoracentesis; disagreements were resolved by
consensus. Articles were categorized as those related to the pre-, intra- and
postprocedural aspects of thoracentesis. RESULTS: Sixty relevant studies were
identified and included. Pre-procedural topics included methods for physician
training and maintenance of skills, such as simulation with direct observation.
Additionally, pre-procedural topics included the finding that moderate
coagulopathies (international normalized ratio less than 3 or a platelet count
greater than 25,000/MUL) and mechanical ventilation did not increase risk of
postprocedural complications. Intraprocedurally, ultrasound use was associated
with lower risk of pneumothorax, while pleural manometry can identify a
nonexpanding lung and may help reduce risk of re-expansion pulmonary edema.
Postprocedurally, studies indicate that routine chest X-ray is unwarranted,
because bedside ultrasound can identify pneumothorax. CONCLUSIONS: While the
performance of thoracentesis is not without risk, clinicians can incorporate
recent advances into practice to mitigate patient harm and improve effectiveness.
Journal of Hospital Medicine 2017;12:266-276.
PMID- 28411294
TI - Hospital Medicine and Perioperative Care: A Framework for High-Quality, High
Value Collaborative Care.
AB - BACKGROUND: Hospitalists have long been involved in optimizing perioperative care
for medically complex patients. In 2015, the Society of Hospital Medicine
organized the Perioperative Care Work Group to summarize this experience and to
develop a framework for providing optimal perioperative care. METHODS: The work
group, which consisted of perioperative care experts from institutions throughout
the United States, reviewed current hospitalist-based perioperative care
programs, compiled key issues in each perioperative phase, and developed a
framework to highlight essential elements to be considered. The framework was
reviewed and approved by the board of the Society of Hospital Medicine. RESULTS:
The Perioperative Care Matrix for Inpatient Surgeries was developed. This matrix
characterizes perioperative phases, coordination, and metrics of success.
Additionally, concerns and potential risks were tabulated. Key questions
regarding program effectiveness were drafted, and examples of models of care were
provided. CONCLUSIONS: The Perioperative Care Matrix for Inpatient Surgeries
provides an essential collaborative framework hospitalists can use to develop and
continually improve perioperative care programs. Journal of Hospital Medicine
2017;12:277-282.
PMID- 28411295
TI - What Are the Chances?
PMID- 28411296
TI - The Value of Using Ultrasound to Rule Out Deep Vein Thrombosis in Cases of
Cellulitis.
PMID- 28411297
TI - Hospitalizations With Observation Services and the Medicare Part A Complex
Appeals Process at Three Academic Medical Centers.
AB - Hospitalists and other providers must classify hospitalized patients as inpatient
or outpatient, the latter of which includes all observation stays. These orders
direct hospital billing and payment, as well as patient out-of-pocket expenses.
The Centers for Medicare & Medicaid Services (CMS) audits hospital billing for
Medicare beneficiaries, historically through the Recovery Audit program. A recent
U.S. Government Accountability Office (GAO) report identified problems in the
hospital appeals process of Recovery Audit program audits to which CMS proposed
reforms. In the context of the GAO report and CMS's proposed improvements, we
conducted a study to describe the time course and process of complex Medicare
Part A audits and appeals reaching Level 3 of the 5-level appeals process as of
May 1, 2016 at 3 academic medical centers. Of 219 appeals reaching Level 3, 135
had a decision--96 (71.1%) successful for the hospitals. Mean total time since
date of service was 1663.3 days, which includes mean days between date of service
and audit (560.4) and total days in appeals (891.3). Government contractors were
responsible for 70.7% of total appeals time. Overall, government contractors and
judges met legislative timeliness deadlines less than half the time (47.7%), with
declining compliance at successive levels (discussion, 92.5%; Level 1, 85.4%;
Level 2, 38.8%; Level 3, 0%). Most Level 1 and Level 2 decision letters (95.2%)
cited time-based (24-hour) criteria for determining inpatient status, despite
70.3% of denied appeals meeting the 24-hour benchmark. These findings suggest
that the Medicare appeals system merits process improvement beyond current
proposed reforms. Journal of Hospital Medicine 2017;12:251-255.
PMID- 28411298
TI - Detecting Sepsis: Are Two Opinions Better Than One?
AB - The diagnosis of sepsis requires that objective criteria be met with a
corresponding subjective suspicion of infection. We conducted a study to
characterize the agreement between different providers' suspicion of infection
and the correlation with patient outcomes using prospective data from a general
medicine ward. Registered nurse (RN) suspicion of infection was collected every
12 hours and compared with medical doctor or advanced practice professional
(MD/APP) suspicion, defined as an existing order for antibiotics or a new order
for blood or urine cultures within the 12 hours before nursing screen time.
During the study period, 1386 patients yielded 11,489 screens, 3744 (32.6%) of
which met at least 2 systemic inflammatory response syndrome (SIRS) criteria.
Infection was suspected by RN and MD/APP in 5.8% of cases, by RN only in 22.2%,
by MD/APP only in 7.2%, and by neither provider in 64.7%. Overall agreement rate
was 80.7% for suspicion of infection (kappa = 0.11, P < 0.001). Progression to
severe sepsis or shock was highest when both providers suspected infection in a
SIRS-positive patient (17.7%), was substantially reduced with single-provider
suspicion (6.0%), and was lowest when neither provider suspected infection (1.5%)
(P < 0.001). Provider disagreement regarding suspected infection is common, with
RNs suspecting infection more often, suggesting that a collaborative model for
sepsis detection may improve timing and accuracy. Journal of Hospital Medicine
2017;12:256-258.
PMID- 28411299
TI - The Core Competencies in Hospital Medicine 2017 Revision. Section 1: Clinical
conditions.
PMID- 28411300
TI - The Core Competencies in Hospital Medicine 2017 Revision. Section 2: Procedures.
PMID- 28411301
TI - The Core Competencies in Hospital Medicine 2017 Revision. Section 3: Healthcare
Systems.
PMID- 28411303
TI - Comparative approaches to same/different abstract-concept learning.
AB - Martinho and Kacelnik (2016) imprinted newly hatched ducklings (Anas
platyrhynchos domestica) with a moving pair of either same or different objects,
and following only one session, the ducklings accurately transferred the
same/different relationship to novel object pairs that maintained the training
relationship. This rapid learning and transfer of the concepts same and different
far outstrips the more gradual learning of these basic concepts by animals in
associative-learning tasks in which reinforcement is given for correct responses.
PMID- 28411302
TI - Common and Species-Specific Effects of Phosphate on Marine Microalgae Fatty Acids
Shape Their Function in Phytoplankton Trophic Ecology.
AB - The use of fatty acids (FA) to infer structure of phytoplankton assemblages and
as indicators of microalgae nutritional value is acquiring relevance in modern
phytoplankton ecology and new advances concerning factors influencing FA
variability among microalgae are demanded. In this regard, the relationship
between phosphorus and FA remains particularly little studied in marine
phytoplankton. In the present study, we focus on phosphate effects on FA from a
diversified set of marine microalgae and provide new insights into the
applicability of FA in phytoplankton trophic ecology. Phosphate deprivation
mainly induced monounsaturated FA production in eight out of nine microalgae and
their changes were species-specific, with palmitoleic acid exhibiting extreme
variation and discriminating between haptophyte classes. The important phosphate
induced and interspecific variability found for oleic acid was perceived as a
concern for the current application of this FA as a trophic position indicator in
grazers. Chloroplast C-16 and C-18 polyunsaturated FA were more affected by
phosphate than C-20 and C-22 highly unsaturated FA (HUFA). The relative stability
of stearidonic acid to phosphate in cryptophytes and haptophytes pinpointed this
FA as a suited marker for both microalgae groups. Taken all species together,
phosphate deprivation and taxonomy accounted for 20.8 and 50.7% of total FA
variation, respectively. HUFA were minimally affected by phosphate indicating
their suitability as indicators of phytoplankton trophic value. The asymptotic
relationship between HUFA and phosphorus cell content suggested mineral
composition (phosphorus) could be more important than HUFA content as attribute
of marine microalgae nutritional value at the species level.
PMID- 28411304
TI - Numbers and brains.
AB - The representation of discrete and continuous quantities appears to be ancient
and pervasive in animal brains. Because numbers are the natural carriers of these
representations, we may discover that in brains, it's numbers all the way down.
PMID- 28411305
TI - Reading charts in ophthalmology.
AB - A new generation of logarithmic reading charts has sparked interest in
standardized reading performance analyses. Such reading charts have been
developed according to the standards of the International Council of
Ophthalmology. The print size progression in these calibrated charts is in
accordance with the mathematical background of EN ISO 8596. These reading charts
are: the Bailey-Lovie Word Reading Chart, the Colenbrander English Continuous
Text Near Vision Cards, the Oculus Reading Probe II, the MNREAD Charts, the
SKread Charts, and the RADNER Reading Charts. The test items used for these
reading charts differ among the charts and are standardized to various extents.
The Bailey-Lovie Charts, MNREAD Charts, SKread Charts, and RADNER Charts are also
meant to measure reading speed and allow determination of further reading
parameters such as reading acuity, reading speed based on reading acuity,
critical print size, reading score, and logMAR/logRAD ratio. Such calibrated
reading charts have already provided valuable insights into the reading
performance of patients in many research studies. They are available in many
languages and thus facilitate international communication about near visual
performance. In the present review article, the backgrounds of these modern
reading charts are presented, and their different levels of test-item
standardization are discussed. Clinical research studies are mentioned, and a
discussion about the immoderately high number of reading acuity notations is
included. Using the logReading Acuity Determination ([logRAD] = reading acuity
equivalent of logMAR) measure for research purposes would give reading acuity its
own identity as a standardized reading parameter in ophthalmology.
PMID- 28411306
TI - Is Fecal Diversion Needed in Pelvic Anastomoses During Hyperthermic
Intraperitoneal Chemotherapy (HIPEC)?
AB - BACKGROUND: The role of fecal diversion with pelvic anastomosis during
cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
(HIPEC) is not well defined. METHODS: A retrospective review of patients who
underwent CRS and HIPEC between 2009 and 2016 was performed to identify those
with a pelvic anastomosis (colorectal, ileorectal, or coloanal anastomosis).
RESULTS: The study identified 73 patients who underwent CRS and HIPEC at three
different institutions between July 2009 and June of 2016. Of these patients, 32
(44%) underwent a primary anastomosis with a diverting ileostomy, whereas 41
(56%) underwent a primary anastomosis without fecal diversion. The anastomotic
leak rate for the no-diversion group was 22% compared with 0% for the group with
a diverting ileostomy (p < 0.01). The 90-day mortality rate for the no-diversion
group was 7.1%. The hospital stay was 14.1 +/- 8.0 days in the diversion group
compared with 17.9 +/- 12.5 days in the no-diversion group (p = 0.12). Of those
patients with a diverting ileostomy, 68% (n = 22) had their bowel continuity
restored, 18% of which required a laparotomy for reversal. Postoperative
complications occurred for 50% of those who required a laparotomy and for 44% of
those who did not require a laparotomy (p = 0.84). CONCLUSION: Diverting
ileostomies in patients with a pelvic anastomosis undergoing CRS and HIPEC are
associated with a significantly reduced anastomotic leak rate. Reversal of the
diverting ileostomy in this patient population required a laparotomy in 18% of
the cases and had an associated morbidity rate of 50%.
PMID- 28411307
TI - Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute
Rejection.
AB - PURPOSE: To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle
(USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection
in pediatric kidney transplant patients. PROCEDURES: The USPIO ferumoxytol has a
long blood half-life and is phagocytosed by macrophages. In an IRB-approved
single-center prospective clinical trial, 26 pediatric patients and adolescents
(age 10-26 years) with acute allograft rejection (n = 5), non-rejecting
allografts (n = 13), and normal native kidneys (n = 8) underwent multi-echo T2*
fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5 mg
Fe/kg ferumoxytol. T2* relaxation times at 4 h p.i. (perfusion phase) and more
than 20 h p.i. (macrophage phase) were compared with biopsy results. The presence
of rejection was assessed using the Banff criteria, and the prevalence of
macrophages on CD163 immunostains was determined based on a semi-quantitative
scoring system. MRI and histology data were compared among patient groups using t
tests, analysis of variance, and regression analyses with a significance
threshold of p < 0.05. RESULTS: At 4 h p.i., mean T2* values were 6.6 +/- 1.5 ms
for native kidneys and 3.9 ms for one allograft undergoing acute immune
rejection. Surprisingly, at 20-24 h p.i., one rejecting allograft showed
significantly prolonged T2* relaxation times (37.0 ms) compared to native kidneys
(6.3 +/- 1.7 ms) and non-rejecting allografts (7.6 +/- 0.1 ms). Likewise, three
additional rejecting allografts showed significantly prolonged T2* relaxation
times compared to non-rejecting allografts at later post-contrast time points, 25
97 h p.i. (p = 0.008). Histological analysis revealed edema and compressed
microvessels in biopsies of rejecting allografts. Allografts with and without
rejection showed insignificant differences in macrophage content on
histopathology (p = 0.44). CONCLUSION: After ferumoxytol administration, renal
allografts undergoing acute rejection show prolonged T2* values compared to non
rejecting allografts. Since histology revealed no significant differences in
macrophage content, the increasing T2* value is likely due to the combined effect
of reduced perfusion and increased edema in rejecting allografts.
PMID- 28411308
TI - The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in
Colorectal Cancer.
AB - 5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal
cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which
decreases the therapeutic potential of 5-FU. Several studies indicated that miR
200c is also involved in chemotherapeutic drug resistance, but the exact
mechanism of miR-200c mediated chemoresistance has not yet been fully understood.
In this study, we examined the effect of inhibition of miR-200c on the
sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA
anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR.
The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin
were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity
were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c
expression in the transfected cells compared with that in the control group. LNA
anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the
presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU
induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker
in CRC, can be a potential therapeutic approach to overcome chemoresistance
during 5-FU chemotherapy.
PMID- 28411309
TI - Calreticulin Mutations in Bulgarian MPN Patients.
AB - Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the
cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs).
We applied four molecular genetic methods for identification of CALR exon 9
mutations, including high resolution melt (HRM) analysis, Sanger sequencing,
semiconductor target genes sequencing and whole exome sequencing. A total of 78
patients with myeloid malignancies were included in the study. We identified 14
CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies.
All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n =
7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon
9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no
statistically significant differences in the hematological parameters between the
cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were
fully concordant in the detection of CALR mutations. This is one of the few
reports on the CALR mutations frequency in South-eastern populations. Our study
shows that the frequency and patterns of these mutations is identical to those in
the patients' cohorts from Western countries. Besides we demonstrated the utility
of four different methods for their detection.
PMID- 28411310
TI - Identifying the D-Pentoses Using Water Adduction to Lithium Cationized Molecule.
AB - A method has been developed that is capable of distinguishing an exhaustive list
of underivatized D-pentoses with only a mass spectrometer. Electrospray
ionization (ESI) of a solution containing a pentose and a lithium salt yields
[Pentose + Li]+. These lithiated pentoses adduct water in a quadrupole ion trap.
The reaction rate of water adduction is unique for several of the pentose
isomers. Additionally, there are multiple potential gas-phase lithiation sites to
form [Pentose + Li]+. A mixture of ions with at least one reactive (water
adducting) and at least one unreactive (non-adducting) lithiation site is formed
for each pentose. The water adduction reaction rate along with the unreactive
fraction of lithiated pentose can be used to completely discriminate all D
pentoses. Graphical Abstract ?.
PMID- 28411311
TI - Total Fluorescence Fingerprinting of Pesticides: A Reliable Approach for
Continuous Monitoring of Soils and Waters.
AB - The present work relates to the creation/extension of a database of Total
Excitation-Emission and Total Synchronous Fluorescence Matrices (TEEMs and TSFMs)
along with optimal Synchronous Fluorescence Spectra (SFS) to fingerprint
pesticides widely used in Morocco. This spectrometric multi-component
fingerprinting may permit the direct detection of pesticides persisting in soil
or water. The objective of the current investigation is to detect four pesticide
remains in agricultural soils by applying the spectrometric fingerprinting
results. They are the commercial: i) insecticide Axlera 5G (carbamate), ii)
fungicide Orsalis 5% SC (triazole), iii) insecticide Force 0,5 G (pyrethrinoid)
and iv) insecticide Proclaim 05 SG (non-assigned). The agricultural plantations
monitored are located in the great agricultural Doukkala region at the western
Atlantic side of Morocco, where these chemicals are in large sale and use.
PMID- 28411312
TI - 2014: The Year of the Sleeve Supremacy.
PMID- 28411313
TI - Roux-En-Y Gastric Bypass and Sleeve Gastrectomy Does Not Affect Food Preferences
When Assessed by an Ad libitum Buffet Meal.
AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to a
reduction in energy intake. It is uncertain whether this reduction is simply due
to eating smaller portions or if surgery changes food preferences towards less
energy-dense food. Previous results rely on verbal reports, which may be prone to
recall bias and underestimation of especially unhealthy foods. METHODS: Using an
ad libitum buffet meal targeting direct behavior, we investigated if RYGB and SG
surgery leads to changes in food preferences. In addition, we assessed food
preferences by a picture display test to explore differences between a method
relying on verbal report and a method assessing direct behavior. RESULTS: Forty
one subjects (BMI 45.0 +/- 6.8 kg/m2) completed a visit pre- and 6 months post
RYGB (n = 31) and SG (n = 10). Mean BMI decreased with 11.7 +/- 0.6 kg/m2 and
total energy intake at the buffet meal with 54% (4491 +/- 208 kJ vs. 2083 +/- 208
kJ, P < 0.001), respectively. However, relative energy intake from the following
food categories: high-fat, low-fat, sweet, savory, high-fat-savory, high-fat
sweet, low-fat-savory, and low-fat-sweet, as well as energy density did not
change following surgery (all P >= 0.18). In contrast, the picture display test
showed that food from the low-fat-savory group was chosen more often post-surgery
(34 +/- 8% vs. 65 +/- 9%, P = 0.02). CONCLUSION: The reduction in energy intake
after RYGB and SG surgery and the subsequent weight loss seems to be primarily
related to a reduction in portion sizes and not by changes in food preferences
towards less energy-dense foods. These results underline the necessity of
investigating eating behavior by targeting direct behavior.
PMID- 28411314
TI - Dental enamel as biomarker for environmental contaminants in relevant
industrialized estuary areas in Sao Paulo, Brazil.
AB - Heavy metal contamination is a long-standing and very well-known public health
problem, and its exposure can cause damage to several organs of human body,
especially on the central nervous system of young children and teenagers. The aim
of this article is to evaluate lead, cadmium, and manganese contamination in 125
children from 6 to 13 years old living in contaminated areas during the period
from 2006 to 2009 (Sao Vicente, Cubatao Downtown, Bertioga and Cubatao
Piloes/Agua Fria). This estuary area is the most important example of
environmental degradation by chemicals from industrial sources. This is a cross
sectional study through clinical examinations and dental enamel tests. All
mothers from these children lived in the area since before the pregnancy. Lead,
cadmium, and manganese levels (MUg/g) were measured on dental enamel samples
through graphite furnace atomic absorption spectrometry, searching for the
occurrence of heavy metals. The mean lead concentrations were 139.48 MUg/g in
Cubatao Piloes/Agua Fria, 170.45 MUg/g in Cubatao Downtown, 213.52 MUg/g in Sao
Vicente, and 151.89 MUg/g in Bertioga. The mean cadmium concentrations were 10.83
MUg/g in Cubatao Piloes/Agua Fria, 12.58 MUg/g in Cubatao Downtown, 10.92 MUg/g
in Sao Vicente, and 14.57 MUg/g in Bertioga. The mean manganese concentrations
were 23.49 MUg/g in Cubatao Piloes/Agua Fria, 30.90 MUg/g in Cubatao Downtown,
41.46 MUg/g in Sao Vicente, and 42.00 MUg/g in Bertioga. Dental surface enamel
may be used as an efficient biomarker of past environmental exposure to lead,
manganese, and cadmium which are associated to well-known sources of heavy metal
contamination. The results suggest that the evaluated children were exposed to
sources of lead, cadmium, and manganese since before their conceptions. Although
Bertioga initially was chosen as a control area of this study, it was also was
verified to have heavy metal contamination on examined children.
PMID- 28411315
TI - Contamination of marine fauna by chlordecone in Guadeloupe: evidence of a seaward
decreasing gradient.
AB - Chlordecone is an organochlorine pesticide, used in the Lesser Antilles from 1972
to 1993 to fight against a banana weevil. That molecule is very persistent in the
natural environment and ends up in the sea with runoff waters. The objective of
the present study is to evaluate the level of contamination in several trophic
groups of marine animals according to their distance from the source of
pollution. Samples of suspended matter, macroalgae, herbivorous fishes,
detrivorous crustaceans, zooplanktivorous fishes, first- and second-order of
carnivorous fishes, and piscivorous fishes have been collected in two sites,
located downstream the contaminated sites (Goyave and Petit-Bourg), in three
marine habitats (coastal mangroves, seagrass beds located 1.5 km from the
shoreline, and coral reefs at 3 km offshore). Animals collected in mangroves were
the most contaminated (mean concentrations 193 MUg kg-1 in Goyave and 213 MUg kg
1 in Petit-Bourg). Samples from seagrass beds presented intermediate
concentrations of chlordecone (85 MUg kg-1 in Goyave and 107 MUg kg-1 in Petit
Bourg). Finally, samples from coral reefs were the less contaminated (71 MUg kg-1
in Goyave and 74 MUg kg-1 in Petit-Bourg). Reef samples, collected 3 km offshore,
were two to three times less contaminated than those collected in mangroves.
PMID- 28411316
TI - Phytoextraction of rare earth elements in herbaceous plant species growing close
to roads.
AB - The aim of study was to determine the phytoextraction of rare earth elements
(REEs) to roots, stems and leaves of five herbaceous plant species (Achillea
millefolium L., Artemisia vulgaris L., Papaver rhoeas L., Taraxacum officinale
AND Tripleurospermum inodorum), growing in four areas located in close proximity
to a road with varied traffic intensity. Additionally, the relationship between
road traffic intensity, REE concentration in soil and the content of these
elements in plant organs was estimated. A. vulgaris and P. rhoeas were able to
effectively transport REEs in their leaves, independently of area collection. The
highest content of REEs was observed in P. rhoeas leaves and T. inodorum roots.
Generally, HREEs were accumulated in P. rhoeas roots and leaves and also in the
stems of T. inodorum and T. officinale, whereas LREEs were accumulated in T.
inodorum roots and T. officinale stems. It is worth underlining that there was a
clear relationship between road traffic intensity and REE, HREE and LREE
concentration in soil. No positive correlation was found between the
concentration of these elements in soil and their content in plants, with the
exception of T. officinale. An effective transport of REEs from the root system
to leaves was observed, what points to the possible ability of some of the tested
plant species to remove REEs from soils near roads.
PMID- 28411317
TI - Race, obesity, and the renin-angiotensin-aldosterone system: treatment response
in children with primary hypertension.
AB - BACKGROUND: Pediatric primary hypertension (HTN) is increasingly recognized, but
the effect of patient characteristics such as obesity and race on treatment
outcomes is not well described. The renin-angiotensin-aldosterone system (RAAS)
may also contribute to HTN. We hypothesized patient parameters of these factors,
including baseline RAAS, influence blood pressure (BP) response to
pharmacological treatment in HTN. METHODS: This was a retrospective cohort of 102
consecutive patients with HTN. Primary outcomes were changes per year in systolic
and diastolic BP (SBP, DBP). Secondary outcome was change per year in left
ventricular mass index (LVMI). We evaluated whether baseline plasma renin
activity (PRA), aldosterone, renin-to-aldosterone ratio, overweight/obesity,
race, initial drug choice, and multidrug therapy were associated with the
outcomes using general linear regression models adjusted for confounding
variables. RESULTS: Racially diverse (43% Hispanic, 28% black, 25% white) and
predominantly overweight/obese (75%) patients were studied. Median length of
follow-up was 14.5 months. Higher baseline aldosterone was associated with
decreased SBP (-1.03 mmHg/year), DBP (-0.95 mmHg/year), and DBP z score (
0.07/year) during the study period. Higher baseline PRA was associated with
decreased SBP z score (-0.04/year) and LVMI (-2.89 g/m2.7/year). Stratified
analyses revealed the relationships between baseline aldosterone and PRA, and
annual reductions in outcomes were strengthened in nonobese and white patients.
CONCLUSIONS: Pretreatment aldosterone and PRA predicted short-term follow-up BP
and LVMI, especially in nonobese and white patients. The RAAS profile could guide
treatment of HTN and suggests consideration of angiotensin-converting enzyme
inhibitors and angiotensin II receptor blockers as first-line treatment options.
PMID- 28411318
TI - Long-term grazing effects on vegetation characteristics and soil properties in a
semiarid grassland, northern China.
AB - Understanding the responses of vegetation characteristics and soil properties to
grazing disturbance is useful for grassland ecosystem restoration and management
in semiarid areas. Here, we examined the effects of long-term grazing on
vegetation characteristics, soil properties, and their relationships across four
grassland types (meadow, Stipa steppe, scattered tree grassland, and sandy
grassland) in the Horqin grassland, northern China. Our results showed that
grazing greatly decreased vegetation cover, aboveground plant biomass, and root
biomass in all four grassland types. Plant cover and aboveground biomass of
perennials were decreased by grazing in all four grasslands, whereas grazing
increased the cover and biomass of shrubs in Stipa steppe and of annuals in
scattered tree grassland. Grazing decreased soil carbon and nitrogen content in
Stipa steppe and scattered tree grassland, whereas soil bulk density showed the
opposite trend. Long-term grazing significantly decreased soil pH and electrical
conductivity (EC) in annual-dominated sandy grassland. Soil moisture in fenced
and grazed grasslands decreased in the following order of meadow, Stipa steppe,
scattered tree grassland, and sandy grassland. Correlation analyses showed that
aboveground plant biomass was significantly positively associated with the soil
carbon and nitrogen content in grazed and fenced grasslands. Species richness was
significantly positively correlated with soil bulk density, moisture, EC, and pH
in fenced grasslands, but no relationship was detected in grazed grasslands.
These results suggest that the soil carbon and nitrogen content significantly
maintains ecosystem function in both fenced and grazed grasslands. However,
grazing may eliminate the association of species richness with soil properties in
semiarid grasslands.
PMID- 28411319
TI - Fifty-year spatiotemporal analysis of landscape changes in the Mont Saint-Hilaire
UNESCO Biosphere Reserve (Quebec, Canada).
AB - Diachronic analysis with a GIS-based classification of land-use changes based on
aerial photographs, orthophotos, topographic maps, geotechnical reports, urban
plans, and using landscape metrics has permitted insight into the driving forces
responsible for landscape fragmentation in the Mont Saint-Hilaire (MSH) Biosphere
Reserve over the period 1958-2015. Although the occurrence of exogenous factors,
such as extreme weather and fires, can have a significant influence on the
fragmentation of the territory in time and space, the accelerated development of
the built environment (+470%) is nevertheless found to be primarily responsible
for landscape fragmentation and the loss of areas formerly occupied by orchards,
agriculture, and woodlands. The landscape metrics used corroborate these results,
with a simplification of the shape of polygons, and once again reveal the
difficulties of harmonizing different land uses. MSH has become somewhat of a
forest island in a sea of residential development and agriculture. To counter
this isolation of fragmented habitat components, forest corridors have been
proposed and developed for the Biosphere Reserve and particularly for the core
area. Two corridors, to the north and south, are used to connect the protected
area and other wooded areas at the regional scale, in order to promote genetic
exchange between populations of various species. In that regard, the forest
buffer zone around the hill continues to play a key role and has great ecological
value for species and ecological preservation and conservation. However,
appropriate management and landscape preservation actions should recognize and
focus on landscape composition and the associated geographical configuration.
PMID- 28411320
TI - Addition of straw from hyperaccumulator plants to cadmium-contaminated soil
increases cadmium uptake by loquat seedlings.
AB - The straw from three different cadmium (Cd) hyperaccumulators (Galinsoga
parviflora, Youngia erythrocarpa, and Solanum photeinocarpum) was added to Cd
contaminated soil, and its effects on plant growth and Cd accumulation in loquat
seedlings were evaluated. Straw from each of G. parviflora, Y. erythrocarpa, and
S. photeinocarpum was added to Cd-contaminated soil before planting seedlings of
two varieties of loquat (Dawuxing and Chuanzao). Addition of straw from G.
parviflora and S. photeinocarpum increased the root and shoot biomasses of both
loquat varieties, compared with that in the control. Addition of straw also
increased Cd uptake by loquat seedlings. The treatments could be ranked, from
highest Cd contents in roots and shoots of loquat seedlings to lowest, as
follows: S. photeinocarpum straw > Y. erythrocarpa straw > G. parviflora straw >
control. All three types of hyperaccumulator straw increased the amount of Cd
extracted by shoots of two loquat seedlings, with the maximum effect in the S.
photeinocarpum straw treatment. Addition of hyperaccumulator straw also resulted
in increased soil invertase, urease, and catalase activities to varying degrees.
Among the three types of hyperaccumulator straw, S. photeinocarpum straw was the
most effective to increase Cd accumulation in loquat seedlings. Therefore, this
material has the potential to increase the phytoremediation capacity of loquat
seedlings in Cd-contaminated orchards.
PMID- 28411321
TI - Endoscopic colloid cyst excision: surgical techniques and nuances.
AB - BACKGROUND: Endoscopic excision of colloid cysts is currently well established as
a minimally invasive and highly effective technique that is associated with less
morbidity in comparison to microsurgical resection. METHODS: Operative charts and
videos of patients undergoing endoscopic colloid cyst excision were retrieved
from the senior author's database of endoscopic procedures and reviewed. This
revealed nine trans-foraminal and three trans-septal procedures. Description of
the surgical techniques was then formulated. CONCLUSIONS: Variation of the
technique is based on the specific patho-anatomical features of the colloid cyst
being resected. For the trans-foraminal approach, we think that the rotational
technique is associated with a more complete removal of the cyst wall and
consequently lower recurrence rate.
PMID- 28411322
TI - I can hear my shunt-audible noises associated with CSF shunts in hydrocephalic
patients.
AB - BACKGROUND: Cerebrospinal fluid (CSF) shunts are life-long implants, and patients
have reported anecdotally on noises associated with their shunts. There is,
however, a marked lack of information regarding acoustic phenomena related to CSF
shunts. METHODS: We identified all patients who had been treated or followed in
our neurosurgical department within a 15-year period from January 2000 up to the
end of 2014. After approval of the local ethics committee all patients who were
cognitively intact were explored by a questionnaire and by personal interview
about acoustic phenomena related to their shunts. RESULTS: Three hundred forty
seven patients were eligible for the survey, and 260 patients completed the
questionnaire. Twenty-nine patients (11.2%) reported on noises raised by their
shunts. All of them experienced short-lasting noises while changing body posture,
mainly from a horizontal to an upright position, or while reclining the head.
Most of the patients reported on soft sounds, but loud and even very loud noises
occurred in some patients. Seventy-six percent of the patients were not bothered
by these noises as they considered it as a normal part of the therapy or as proof
that the shunt device was functioning. Modern valves with gravitational units are
prone to produce noises in young adults, but nearly all valve types can evoke
noises. CONCLUSIONS: Noises caused by a shunt do occur in a considerable number
of patients with shunts. One should be aware of this phenomenon, and these
patients must be taken seriously.
PMID- 28411323
TI - Practice patterns for the prophylaxis and treatment of acute radiation dermatitis
in the United States.
AB - PURPOSE: Due to the inconclusive evidence for available treatment options,
management of radiation dermatitis (RD) varies among practitioners. This study
defines and reviews the current treatment patterns for RD in the USA, providing
guidance for practicing physicians as well as directions for future research.
METHODS: An online survey of 21 questions was emailed to all 5626 members of the
2013 American Society for Radiation Oncology (ASTRO) directory, which included
radiation oncologists, residents, fellows, physician assistants, nurse
practitioners, registered nurses and other care providers. The questions were
designed to evaluate demographics of responders, their training and comfort in
the management RD, and their patterns of care regarding prophylaxis and treatment
of RD. Data was analyzed using simple summary and descriptive statistics.
RESULTS: Out of the 5626 emails sent, we were left with 709 physician respondents
for our analysis, or a response rate of 12.9%. Although 84.7% of physicians felt
that RD had a moderate or large impact on patients' quality of life during cancer
treatment, only 30.1% received special training or specific instructional courses
in treating RD during their medical training in residency or fellowship. Eighty
nine percent of surveyed physicians rely on observational and/or anecdotal
findings to guide treatment decisions, and 51.4% reported using evidence-based
treatments. CONCLUSION: The results of our study show that there is great
variability in the topical agents and dressings used in practice by radiation
oncologists to prevent and treat RD. This information may be useful to other
practitioners to develop their own personal recommendations and can guide further
research into strategies to prevent and treat radiation dermatitis.
PMID- 28411325
TI - A literature update elucidating production of Panax ginsenosides with a special
focus on strategies enriching the anti-neoplastic minor ginsenosides in ginseng
preparations.
AB - Ginseng, an oriental gift to the world of healthcare and preventive medicine, is
among the top ten medicinal herbs globally. The constitutive triterpene saponins,
ginsenosides, or panaxosides are attributed to ginseng's miraculous efficacy
towards anti-aging, rejuvenating, and immune-potentiating benefits. The major
ginsenosides such as Rb1, Rb2, Rc, Rd., Re, and Rg1, formed after extensive
glycosylations of the aglycone "dammaranediol," dominate the chemical profile of
this genus in vivo and in vitro. Elicitations have successfully led to
appreciable enhancements in the production of these major ginsenosides. However,
current research on ginseng biotechnology has been focusing on the enrichment or
production of the minor ginsenosides (the less glycosylated precursors of the
major ginsenosides) in ginseng preparations, which are either absent or are
produced in very low amounts in nature or via cell cultures. The minor
ginsenosides under current scientific scrutiny include diol ginsenosides such as
Rg3, Rh2, compound K, and triol ginsenosides Rg2 and Rh1, which are being touted
as the next "anti-neoplastic pharmacophores," with better bioavailability and
potency as compared to the major ginsenosides. This review aims at describing the
strategies for ginsenoside production with special attention towards production
of the minor ginsenosides from the major ginsenosides via microbial
biotransformation, elicitations, and from heterologous expression systems.
PMID- 28411324
TI - Determinants of social competence in pediatric brain tumor survivors who
participated in an intervention study.
AB - PURPOSE: This prospective study describes disease/treatment, personal
characteristics, and social/family contextual variables as risk and resilience
factors that predict social competence in pediatric brain tumor survivors (PBTS).
METHODS: Ninety-one PBTS (51% male, mean age 11.21 years, off-treatment,
attending a regular classroom >50% of the time) participated. PBTS and their
primary caregivers (proxy) completed the Social Skills Rating System (SSRS) to
assess social competence at baseline, 2, and 8 months follow-up. At baseline,
medical information (e.g., tumor type and location, cranial irradiation therapy
(CIT)), personal characteristics (e.g., child's age and gender, intelligence,
executive function, attention, and memory), and social/family factors (family
income and ethnicity) were obtained. RESULTS: Using mixed model multivariable
analyses with a longitudinal component, tumor type (medulloblastoma) (p < 0.01)
and poor executive function, specifically, emotional control, were the best
predictors of low total and assertion self-reported SSRS scores (p < 0.02).
Receiving CIT was associated with low proxy-reported assertion (p = 0.035), and
cooperation score (p = 0.02). Poor emotional control was associated with low
proxy-reported total (p = 0.032), assertion (p = 0.023), and self-control scores
(p = 0.007). Being non-White was associated with low proxy-reported total (p =
0.016), self-control (p = 0.040), responsibility (p = 0.035), and cooperation
scores (p = 0.002). There were no significant changes over time. CONCLUSIONS:
This study supports a multifactorial model of insult and non-insult factors
(medical, personal, and social context) as determinants of social competence in
PBTS. Data from both informants identify determinants of social competence. These
factors need to be considered in future interventions to help children better
improve their social competence.
PMID- 28411326
TI - Neck Muscle EMG-Force Relationship and Its Reliability During Isometric
Contractions.
AB - BACKGROUND: Susceptible to injury, the neck is subject to scientific
investigations, frequently aiming to elucidate possible injury mechanisms via
surface electromyography (EMG) by indirectly estimating cervical loads. Accurate
estimation requires that the EMG-force relationship is known and that its
measurement error is quantified. Hence, this study examined the relationship
between EMG and isometric force amplitude of the anterior neck (AN), the upper
posterior neck (UPN), and the lower posterior neck (LPN) and then assessed the
relationships' test-retest reliability across force-percentiles within and
between days. METHODS: EMG and force data were sampled from 18 participants
conducting randomly ordered muscle contractions at 5-90% of maximal voluntary
force during three trials over 2 days. EMG-force relationships were modeled with
general linear mixed-effects regression. Overall fitted lines' between-trial
discrepancies were evaluated. Finally, the reliability of participants' fitted
regression lines was quantified by an intraclass correlation coefficient (ICC)
and the standard error of measurement (SEM). RESULTS: A rectilinear model had the
best fit for AN while positively oriented quadratic models had the best fit for
UPN and LPN, with mean adjusted conditional coefficients of determination and
root mean square errors of 0.97-0.98 and 4-5%, respectively. Overall EMG-force
relationships displayed a maximum 6% between-trial discrepancy and over 20% of
maximal force, and mean ICC was above 0.79 within day and 0.27-0.61 between days
across areas. Corresponding SEM was below 12% both within and between days across
areas, excluding UPN between days, for which SEM was higher. CONCLUSIONS: EMG
force relationships were elucidated for three neck areas, and provided models
allow inferences to be drawn from EMG to force on a group level. Reliability of
EMG-force relationship models was higher within than between days, but typically
acceptable for all but the lowest contraction intensities, and enables adjustment
for measurement imprecision in future studies.
PMID- 28411327
TI - Racial Differences in Mental Health Recovery among Veterans with Serious Mental
Illness.
AB - Black consumers with serious mental illness (SMI) face significant challenges in
obtaining quality mental health care and are at risk for experiencing significant
disparities in mental health care outcomes, including recovery from mental
illness. Patient-provider interactions may partly contribute to this disparity.
The purpose of the current study was to understand the effects of race,
psychosis, and therapeutic alliance on mental health recovery orientation among
Veterans with SMI. Participants were Veterans who had an SMI being treated at two
Veteran Affairs outpatient mental health clinics by a psychiatrist or nurse
practitioner. Participants completed the Behavior and Symptom Identification
Scale (BASIS-24), Mental Health Recovery Measure, and patient-report Scale to
Assess the Therapeutic Relationship (STAR-P) which includes three subscales:
positive collaboration, positive clinician input, and non-supportive clinician
input. Regression analyses were used to determine interactive effects of race,
psychosis severity, and therapeutic alliance variables. The sample was 226
Veterans (50% black, 50% white). Black participants were slightly older (p <
.05), had higher baseline psychosis (p < .05), higher mental health recovery (p <
.05), and perceived less non-supportive clinician input (p < .01) than white
participants. Regression analyses indicated a significant three-way interaction
among race, psychosis, and positive collaboration (p < .01). Greater positive
collaboration attenuated the negative effect of higher levels of psychosis on
mental health recovery orientation for black participants. Conversely, for white
participants, positive collaboration had little effect on the negative
relationship between psychosis severity and mental health recovery orientation.
Increased levels of psychosis may inhibit patients' perceptions of their ability
to recover from SMI. However, for black participants, positive collaboration with
mental health providers may moderate the effects of psychotic symptomatology.
PMID- 28411328
TI - Dance and Hometown Associations are Promising Strategies to Improve Physical
Activity Participation Among US Nigerian Transnational Immigrants.
AB - OBJECTIVE: Lack of physical activity participation has been identified as a
determinant for negative health outcomes across various ethnicities worldwide and
within the USA. We investigated the perceptions of the prospects of promoting
dancing within hometown associations as a form for improving physical activity
participation for Nigerian Transnational Immigrants (NTIs) in the USA: a migrant
cohort subset of individuals who maintain cross-border ties with their indigenous
communities of origin. METHOD: Using PEN-3 cultural model, we conducted semi
structured interviews with 24 transnational African migrants (11 males and 13
females) living in Chicago to explore culturally sensitive strategies to promote
physical activity participation among our target population. RESULTS: The
findings revealed positive perceptions related to dancing that might help to
promote physical activity (PA) among NTI, existential or unique perceptions
related to Nigerian parties that may also play a role with PA promotion, and
negative perception in the form of limited discussions about PA in Nigerian
hometown associations in the USA. CONCLUSION: Results from this study highlight
the need for further investigation on culturally sensitive strategies to improve
physical activity and participation in diverse Black immigrant populations,
specifically in the form of cultural dance and activities such as parties in
which this population frequently participate in. Furthermore, hometown
associations may also serve as a platform for the implementation of PA programs
due to its large reach to a rather covert group.
PMID- 28411329
TI - Racial and Ethnic Difference in Falls Among Older Adults: Results from the
California Health Interview Survey.
AB - BACKGROUND: Research suggests that fall risk among older adults varies by
racial/ethnic groups; however, few studies have examined fall risk among
Hispanics and Asian American older adults. METHODS: Using 2011-2012 California
Health Interview Survey data, this study examines falling >=2 times in the past
year by racial/ethnic groups (Asian Americans, Hispanics, and Blacks) aged >=65,
adjusting for socio-demographic characteristics, body mass index, co-morbidities,
and functional limitations. A secondary analysis examines differences in fall
risk by English language proficiency and race/ethnicity among Asian Americans and
Hispanics. RESULTS: Asian Americans were significantly less likely to fall
compared to non-Hispanic whites, individuals with >=2 chronic diseases were
significantly more likely to fall than individuals with <2 chronic diseases, and
many functional limitations were significantly associated with fall risk, when
adjusting for all factors. African Americans and Hispanics did not differ
significantly from non-Hispanic whites. Analysis adjusting for race/ethnicity and
English language proficiency found that limited English proficient Asian
Americans were significantly less likely to fall compared to non-Hispanic whites,
individuals with >=2 chronic diseases were significantly more likely to fall than
individuals with <2 chronic diseases, and all functional limitations were
significantly associated with fall risk, when adjusting for all factors. No
differences were found when examining by racial/ethnic and English
proficient/limited English proficient groups. CONCLUSION: Further research is
needed to explore factors associated with fall risks across racial/ethnic groups.
Culturally relevant and targeted interventions are needed to prevent falls and
subsequent injuries in the increasingly diverse aging population in the USA.
PMID- 28411330
TI - A Restorative Yoga Intervention for African-American Breast Cancer Survivors: a
Pilot Study.
AB - BACKGROUND: Data show that yoga is effective for improving health-related
outcomes in breast cancer survivors. While breast cancer is the most commonly
diagnosed cancer among African-American women (AAW), AAW are less likely to
engage in yoga compared to other ethnic groups. The goals of the current study
were to assess the feasibility of an 8-week restorative yoga program among
African-American breast cancer survivors (AA BCS). Specifically, study aims were
to (1) measure changes in study outcomes in a restorative yoga (RY) group
compared to a wait list control group, (2) assess adherence to the RY program,
and (3) assess program satisfaction among study participants. METHODS: Thirty
three AA BCS were randomly assigned to either the RY intervention (n = 18) or
wait list control group (n = 15). RY classes met once per week for 8 weeks. Pre-
and post-testing assessments were measured at 0 and 8 weeks (immediately post
intervention). RESULTS: Depression scores at follow-up were significantly lower
in the yoga group (M = 4.78, SD = 3.56) compared to the control group (M = 6.91,
SD = 5.86). No significant group differences were observed for sleep quality,
fatigue, or perceived stress. Yoga program participants completing baseline
assessments demonstrated 61% adherence to the yoga classes. Average rating of the
yoga program was "very useful." Recommendations for future yoga programs were
provided. CONCLUSIONS: This study suggests that yoga has a beneficial effect on
depression in AA BCS. There is, however, a need to further explore the benefits
of yoga among minority breast cancer survivors using a study with larger sample
sizes.
PMID- 28411331
TI - Glutaric Acidemia Type 1: A Case of Infantile Stroke.
AB - BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited
metabolic disorder which is associated with GCDH gene mutations which alters the
glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of
the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are
often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT:
A 9-month-old male infant referred to our department with focal tonic-clonic
seizures during rotavirus infection and acute infarcts in MRI. Clinical
manifestation, MRI findings, and metabolic investigations directed thoughts
towards GA-I. Molecular genetic testing revealed a homozygous c.572T>C (p.M191T)
mutation in GCDH gene which confirmed the diagnosis. Application of protein
restricted diet, carnitine and riboflavin supplementations prevented the
progression of Magnetic Resonance Imaging (MRI) and clinical pathologic findings
during the 1 year of follow-up period. CONCLUSION: This case is of great
importance since it shows possibility of infantile stroke in GA-1, significance
of early diagnosis and phenotypic variability of disease.
PMID- 28411332
TI - Evaluation of Rosin Gum and Eudragit(r) RS PO as a Functional Film Coating
Material.
AB - Polymers are essential tools in the research and development of new therapeutic
devices. The diversity and flexibility of these materials have generated high
expectations in the composition of new materials with extraordinary abilities,
especially in the design of new systems for the modified release of
pharmaceutically active ingredients. The natural polymer rosin features moisture
protection and pH-dependent behavior (i.e., it is sensitive to pH > 7.0),
suggesting its possible use in pharmaceutical systems. The synthetic polymer
Eudragit(r) RS PO is a low-permeability material, the disintegration of which
depends on the time of residence in the gastrointestinal tract. The present study
developed a polymeric material with desirable physicochemical characteristics and
synergistic effects that resulted from the inherent properties of the associated
polymers. Isolated films were obtained by solvent evaporation and subjected to a
water vapor transmission test, scanning electron microscopy, calorimetry, Fourier
transform-infrared (FT-IR) spectroscopy, micro-Raman spectroscopy, and mechanical
analysis. The new polymeric material was macroscopically continuous and
homogeneous, was appropriately flexible, had low water permeability, was
vulnerable in alkaline environments, and was thermally stable, maintaining an
unchanged structure up to temperatures of ~400 degrees C. The new material also
presented potentially suitable characteristics for application in film coatings
for oral solids, suggesting that it is capable of carrying therapeutic substances
to distal regions of the gastrointestinal tract. These findings indicate that
this new material may be added to the list of functional excipients.
PMID- 28411333
TI - Technological Device for Manufacturing Transdermal Films: Possible Applications
to the Individualized Treatment for Erectile Dysfunction.
AB - Pharmacological advances in erectile dysfunction (ED) treatment have aroused
growing interest among health professionals towards sexual dysfunction,
generating an increasing demand for dosage forms and drug delivery systems,
including tadalafil. This study aimed to develop a device to generate patches
that would enable drug dosage individualization and transdermal administration.
To create such a mechanical device, technical drawings were made using the CAD
software. A functional prototype was built, and a pharmaceutical formulation
containing tadalafil (10 mg cm-2) was prepared. An analytical method (HPLC) was
developed and validated. The average weight of adhesives (n = 10) was 241.01 mg;
the content uniformity for preparations in unit doses (n = 10) was 108.93%, and a
CV <2% for intraadhesive tadalafil content (n = 40) was observed. The ex vivo
permeation of patches containing tadalafil was determined in Franz cells (n = 6),
equipped with human skin and kept for 12 h in contact with the patch, by using
the tape stripping method. The optimized method showed acceptable confidence
limits within the range recommended by regulatory agencies, being validated for
use in this ex vivo permeation study. Tadalafil could permeate to the viable
epidermis and dermis (5.7%). The created device produced homogeneous patches of
tadalafil, showing such technological innovation as to be feasible in
individualized therapy for the treatment of ED.
PMID- 28411334
TI - Normative values for a tablet computer-based application to assess chromatic
contrast sensitivity.
AB - Tablet computer displays are amenable for the development of vision tests in a
portable form. Assessing color vision using an easily accessible and portable
test may help in the self-monitoring of vision-related changes in ocular/systemic
conditions and assist in the early detection of disease processes. Tablet
computer-based games were developed with different levels of gamification as a
more portable option to assess chromatic contrast sensitivity. Game 1 was
designed as a clinical version with no gaming elements. Game 2 was a gamified
version of game 1 (added fun elements: feedback, scores, and sounds) and game 3
was a complete game with vision task nested within. The current study aimed to
determine the normative values and evaluate repeatability of the tablet computer
based games in comparison with an established test, the Cambridge Colour Test
(CCT) Trivector test. Normally sighted individuals [N = 100, median (range) age
19.0 years (18-56 years)] had their chromatic contrast sensitivity evaluated
binocularly using the three games and the CCT. Games 1 and 2 and the CCT showed
similar absolute thresholds and tolerance intervals, and game 3 had significantly
lower values than games 1, 2, and the CCT, due to visual task differences. With
the exception of game 3 for blue-yellow, the CCT and tablet computer-based games
showed similar repeatability with comparable 95% limits of agreement. The custom
designed games are portable, rapid, and may find application in routine clinical
practice, especially for testing younger populations.
PMID- 28411335
TI - Development of a puff- and suction-type pressure stimulator for human tactile
studies.
AB - In this study, we developed a tactile stimulator capable of administering either
puff- or suction-type stimuli. The system is composed of three parts: a control
unit, an air-handling unit, and a stimulation unit. The control unit controls the
type, intensity, and time of stimulation. The air-handling unit delivers the
stimulation power quantitatively to the stimulation unit, as commanded by the
control unit. The stimulation unit stably administers either type of pressure to
the skin, without any change of the tactor. Although the design of the stimulator
is simple, it allows for five levels of control of the stimulation intensity (2-6
psi) and 0.1-s steps of control of the stimulation time, as we confirmed by
tests. Preliminary electroencephalographic and event-related potential (ERP)
studies of our system in humans confirmed the presence of N100 and P300 waves at
standard electrode position C3, which are related to perception and cognition,
respectively, in the somatosensory area of the brain. In addition, different
stimulation types (puff and suction) and intensities (2 and 6 psi) were reflected
in different peak-to-peak amplitudes and slopes of the mean ERP signal. The
system developed in this study is expected to contribute to human tactile studies
by providing the ability to administer puff- or suction-type stimuli
interchangeably.
PMID- 28411337
TI - Protocols for the obvious: Where does it start, and stop?
AB - Protocols can be helpful in specific situations and may have show benefits in
clinical trials. So-called evidence based protocols and checklists frequently
remind clinicians to do the obvious, but may also contain as part of a bundle,
elements that are not based on the best current evidence. However, so called
quality improvement programs frequently call for implementation of the total
bundle. We think this is basically wrong and warn against that practice.
PMID- 28411336
TI - FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas.
AB - PET using 18F-FDG for treatment monitoring in patients with lymphoma is one of
the most well-developed clinical applications. PET/CT is nowadays used during
treatment to assess chemosensitivity, with response-adapted therapy given
according to 'interim' PET in clinical practice to adults and children with
Hodgkin lymphoma. PET is also used to assess remission from disease and to
predict prognosis in the pretransplant setting. Mature data have been reported
for the common subtypes of aggressive B-cell lymphomas, with more recent data
also supporting the use of PET for response assessment in T-cell lymphomas. The
Deauville five-point scale incorporating the Deauville criteria (DC) is
recommended for response assessment in international guidelines. FDG uptake is
graded in relation to the reference regions of normal mediastinum and liver. The
DC have been validated in most lymphoma subtypes. The DC permit the threshold for
adequate or inadequate response to be adapted according to the clinical context
or research question. It is important for PET readers to understand how the DC
have been applied in response-adapted trials for correct interpretation and
discussion with the multidisciplinary team. Quantitative methods to perform PET
in standardized ways have also been developed which may further improve response
assessment including a quantitative extension to the DC (qPET). This may have
advantages in providing a continuous scale to refine the threshold for
adequate/inadequate response in specific clinical situations or treatment
optimization in trials. qPET is also less observer-dependent and limits the
problem of optical misinterpretation due to the influence of background activity.
PMID- 28411338
TI - Shoulder Bankart lesion with posterior instability: A case report of ultrasound
detection.
AB - Minor instability of the shoulder has recently drawn attention as a cause of
shoulder pain in athletes. However, it is difficult to correctly diagnose the
direction in which the humeral head translates and subluxates, and to clarify the
pathology of the instability. We present a case of a 20-year-old male with an
unstable shoulder who could not raise his left arm due to pain. Since 6 years
prior to the onset of pain, the patient could asymptomatically perform voluntary
subluxation, but it was slight and the direction of the subluxation could not be
confirmed. On physical examination, the conventional apprehension test and
Castagna test were positive, but the jerk test was negative. Imaging studies
including arthroscopy showed a Bankart lesion associated with anterior labrum
detachment. There was no posterior Bankart lesion. Due to painful anterior
shoulder instability, arthroscopic Bankart repair was successfully done; however,
9 months later the patient began experiencing symptomatic subluxation of the
shoulder. At this time, the conventional apprehension test and Castagna test were
both negative. It was difficult to detect the direction of the subluxation, just
like in the preoperative condition. We performed an ultrasonographic examination
from the posterior side; this clearly revealed the posterior subluxation
mechanism as posterior slide of the humeral head and anterior shift of the
glenoid. Based on these findings, we modified the rehabilitation and the
subluxation resolved. This case suggests that ultrasound imaging can be an
effective practical option for evaluating shoulder instability, especially in
cases of slight posterior subluxation.
PMID- 28411339
TI - Validation of a novel endoscopic program for measuring the size of
gastrointestinal lesions.
AB - BACKGROUND: Valid and reliable methods for measurement of lesion sizes during
endoscopy have not been established. METHODS: We developed a novel software
program (ENDOVER; Poinbionics, Seoul, Republic of Korea) to measure lesions sizes
and assessed its validity and reliability. To validate the program, we measured
standard coin sizes and estimated measurement errors. To assess program
reliability, 32 pictures of endoscopically resected specimens were used to
measure tissue sizes six times in a 24-h interval by two examiners. Intraclass
correlation coefficients (ICCs) were used to assess intraobserver and
interobserver agreements. Agreement between the program and pathological
measurements was assessed by absolute differences. RESULTS: The nominal standard
sizes of 10-won, 100-won, and 500-won coins were 18.0, 24.0, and 26.5 mm, and the
calculated sizes were 18.09, 24.48, and 26.31 mm, respectively. ICCs of the long
and short diameters were, respectively, 0.92 [95% confidence interval (CI) 0.87
0.95] and 0.93 (CI 0.89-0.96) for examiner 1 and 0.88 (CI 0.81-0.93) and 0.92 (CI
0.87-0.95) for examiner 2. Interobserver ICCs of the long and short diameters
were 0.97 (CI 0.94-0.99) and 0.97 (CI 0.94-0.99), respectively. The mean absolute
differences between the program and pathological measurements were 4.4 and 4.7 mm
for the long and short diameters, respectively. CONCLUSIONS: Our findings
indicate that the novel measurement program is a valid and reliable method for
estimation of lesion sizes from endoscopic findings during and after examination.
PMID- 28411340
TI - Attainment and retention of force moderation following laparoscopic resection
training with visual force feedback.
AB - BACKGROUND: Laparoscopic training with visual force feedback can lead to
immediate improvements in force moderation. However, the long-term retention of
this kind of learning and its potential decay are yet unclear. METHODS: A
laparoscopic resection task and force sensing apparatus were designed to assess
the benefits of visual force feedback training. Twenty-two male university
students with no previous experience in laparoscopy underwent relevant FLS
proficiency training. Participants were randomly assigned to either a control or
treatment group. Both groups trained on the task for 2 weeks as follows: initial
baseline, sixteen training trials, and post-test immediately after. The treatment
group had visual force feedback during training, whereas the control group did
not. Participants then performed four weekly test trials to assess long-term
retention of training. Outcomes recorded were maximum pulling and pushing forces,
completion time, and rated task difficulty. RESULTS: Extreme maximum pulling
force values were tapered throughout both the training and retention periods.
Average maximum pushing forces were significantly lowered towards the end of
training and during retention period. No significant decay of applied force
learning was found during the 4-week retention period. Completion time and rated
task difficulty were higher during training, but results indicate that the
difference eventually fades during the retention period. Significant differences
in aptitude across participants were found. CONCLUSIONS: Visual force feedback
training improves on certain aspects of force moderation in a laparoscopic
resection task. Results suggest that with enough training there is no significant
decay of learning within the first month of the retention period. It is essential
to account for differences in aptitude between individuals in this type of
longitudinal research. This study shows how an inexpensive force measuring system
can be used with an FLS Trainer System after some retrofitting. Surgical
instructors can develop their own tasks and adjust force feedback levels
accordingly.
PMID- 28411341
TI - 25th International Congress of the European Association for Endoscopic Surgery
(EAES) Frankfurt, Germany, 14-17 June 2017 : Poster Presentations.
PMID- 28411342
TI - Mesh fixation in endoscopic inguinal hernia repair: evaluation of methodology
based on a systematic review of randomised clinical trials.
AB - BACKGROUND: The issue of mesh fixation in endoscopic inguinal hernia repair is
frequently debated and still no conclusive data exist on differences between
methods regarding long-term outcome and postoperative complications. The quantity
of trials and the simultaneous lack of high-quality evidence raise the question
how future trials should be planned. METHODS: PubMed, EMBASE and the Cochrane
Library were searched, using the filters "randomised clinical trials" and
"humans". Trials that compared one method of mesh fixation with another fixation
method or with non-fixation in endoscopic inguinal hernia repair were eligible.
To be included, the trial was required to have assessed at least one of the
following primary outcome parameters: recurrence; surgical site infection;
chronic pain; or quality-of-life. RESULTS: Fourteen trials assessing 2161
patients and 2562 hernia repairs were included. Only two trials were rated as low
risk for bias. Eight trials evaluated recurrence or surgical site infection; none
of these could show significant differences between methods of fixation. Two of
11 trials assessing chronic pain described significant differences between
methods of fixation. One of two trials evaluating quality-of-life showed
significant differences between fixation methods in certain functions.
CONCLUSION: High-quality evidence for differences between the assessed mesh
fixation techniques is still lacking. From a socioeconomic and ethical point of
view, it is necessary that future trials will be properly designed. As small- and
medium-sized single-centre trials have proven unable to find answers, register
studies or multi-centre studies with an evident focus on methodology and study
design are needed in order to answer questions about mesh fixation in inguinal
hernia repair.
PMID- 28411343
TI - A modified uncut Roux-en-Y anastomosis in totally laparoscopic distal
gastrectomy: preliminary results and initial experience.
AB - OBJECTIVE: To investigate the safety and feasibility of totally laparoscopic
uncut Roux-en-Y anastomosis in the distal gastrectomy with D2 dissection for
gastric cancer. We also summarized the preliminary experience of totally
laparoscopic uncut Roux-en-Y anastomosis. METHODS: A retrospective analysis was
done in 51 cases of total laparoscopic uncut Roux-en-Y anastomosis in the distant
gastrectomy with D2 dissection for gastric cancer in our hospital from September
2014 to December 2015. RESULTS: All of 51 cases underwent total laparoscopic
uncut Roux-en-Y anastomosis. All the procedures were performed successfully.
There were neither conversions to open surgery nor intraoperative complications
in all 51 cases. In this study, the median operative time was 170 (135-210) min
and the median time of anastomosis was 27 (24-41) min. The blood loss was 60 (30
110) ml. The time to flatus and length of postoperative hospital stay were 2 (1
3) days, and 8 (7-12) days, respectively. The mean lymph node harvest was 34 (18
49). One anastomotic bleeding occurred postoperatively which was cured by
conservative treatment. No major postoperative complication occurred, such as
anastomotic leak, anastomotic stenosis, and Roux stasis syndrome. After a short
term follow-up, no recanalization or reflux gastritis was encountered by
endoscopy. CONCLUSION: The totally laparoscopic uncut Roux-en-Y anastomosis in
distal gastrectomy with lymph node dissection for gastric cancer is safe and
feasible, with a very low rate of recanalization and reflux gastritis.
PMID- 28411344
TI - The effect of a novel minimally invasive strategy for infected necrotizing
pancreatitis.
AB - BACKGROUND: Step-up approach consisting of multiple minimally invasive techniques
has gradually become the mainstream for managing infected pancreatic necrosis
(IPN). In the present study, we aimed to compare the safety and efficacy of a
novel four-step approach and the conventional approach in managing IPN. METHODS:
According to the treatment strategy, consecutive patients fulfilling the
inclusion criteria were put into two time intervals to conduct a before-and-after
comparison: the conventional group (2010-2011) and the novel four-step group
(2012-2013). The conventional group was essentially open necrosectomy for any
patient who failed percutaneous drainage of infected necrosis. And the novel
drainage approach consisted of four different steps including percutaneous
drainage, negative pressure irrigation, endoscopic necrosectomy and open
necrosectomy in sequence. The primary endpoint was major complications (new-onset
organ failure, sepsis or local complications, etc.). Secondary endpoints included
mortality during hospitalization, need of emergency surgery, duration of organ
failure and sepsis, etc. RESULTS: Of the 229 recruited patients, 92 were treated
with the conventional approach and the remaining 137 were managed with the novel
four-step approach. New-onset major complications occurred in 72 patients (78.3%)
in the two-step group and 75 patients (54.7%) in the four-step group (p < 0.001).
For other important endpoints, although there was no statistical difference in
mortality between the two groups (p = 0.403), significantly fewer patients in the
four-step group required emergency surgery when compared with the conventional
group [14.6% (20/137) vs. 45.6% (42/92), p < 0.001]. In addition, stratified
analysis revealed that the four-step approach group presented significantly lower
incidence of new-onset organ failure and other major complications in patients
with the most severe type of AP. CONCLUSION: Comparing with the conventional
approach, the novel four-step approach significantly reduced the rate of new
onset major complications and requirement of emergency operations in treating
IPN, especially in those with the most severe type of acute pancreatitis.
PMID- 28411345
TI - An appraisal of the learning curve in robotic general surgery.
AB - BACKGROUND: Robotic-assisted surgery is used with increasing frequency in general
surgery for a variety of applications. In spite of this increase in usage, the
learning curve is not yet defined. This study reviews the literature on the
learning curve in robotic general surgery to inform adopters of the technology.
METHODS: PubMed and EMBASE searches yielded 3690 abstracts published between July
1986 and March 2016. The abstracts were evaluated based on the following
inclusion criteria: written in English, reporting original work, focus on general
surgery operations, and with explicit statistical methods. RESULTS: Twenty-six
full-length articles were included in final analysis. The articles described the
learning curves in colorectal (9 articles, 35%), foregut/bariatric (8, 31%),
biliary (5, 19%), and solid organ (4, 15%) surgery. Eighteen of 26 (69%) articles
report single-surgeon experiences. Time was used as a measure of the learning
curve in all studies (100%); outcomes were examined in 10 (38%). In 12 studies
(46%), the authors identified three phases of the learning curve. Numbers of
cases needed to achieve plateau performance were wide-ranging but overlapping for
different kinds of operations: 19-128 cases for colorectal, 8-95 for
foregut/bariatric, 20-48 for biliary, and 10-80 for solid organ surgery.
CONCLUSION: Although robotic surgery is increasingly utilized in general surgery,
the literature provides few guidelines on the learning curve for adoption. In
this heterogeneous sample of reviewed articles, the number of cases needed to
achieve plateau performance varies by case type and the learning curve may have
multiple phases as surgeons add more complex cases to their case mix with growing
experience. Time is the most common determinant for the learning curve. The
literature lacks a uniform assessment of outcomes and complications, which would
arguably reflect expertise in a more meaningful way than time to perform the
operation alone.
PMID- 28411347
TI - Pure 3D laparoscopic living donor right hemihepatectomy in a donor with separate
right posterior and right anterior hepatic ducts and portal veins.
AB - BACKGROUND: Despite increases in the performance of pure laparoscopic living
donor hepatectomy, variations in the bile duct or portal vein have been regarded
as relative contraindications to this technique [1-3]. This report describes a
donor with separate right posterior and right anterior hepatic ducts and portal
veins who underwent pure laparoscopic living donor right hemihepatectomy,
integrated with 3D laparoscopy and indocyanine green (ICG) near-infrared
fluorescence cholangiography [1, 4, 5]. METHODS: A 50-year-old man offered to
donate part of his liver to his older brother, who required a transplant for
hepatitis B-associated liver cirrhosis and hepatocellular carcinoma. Donor height
was 178.0 cm, body weight was 82.7 kg, and body mass index was 26.1 kg/m2.
Preoperative computed tomography and magnetic resonance cholangiopancreatography
showed that the donor had separate right posterior and right anterior hepatic
ducts and portal veins. The entire procedure was performed under 3D laparoscopic
view. Following intravenous injections of 0.05 mg/kg ICG, ICG near-infrared
fluorescence camera was used to demarcate the exact transection line and
determine the optimal bile duct division point. RESULTS: The total operation time
was 443 min; the donor required no transfusions and experienced no intraoperative
complications. The graft weighed 1146 g with a graft-to-recipient weight ratio of
1.88%. The optimal bile duct division point was identified using ICG fluorescence
cholangiography, and the bile duct was divided with good patency without any
stricture. The right anterior and posterior portal veins were transected with
endostaplers without any torsion. The patient was discharged on postoperative day
8, with no complications. CONCLUSION: Using a 3D view and ICG fluorescence
cholangiography, pure 3D laparoscopic living donor right hemihepatectomy is
feasible in a donor with separate right posterior and right anterior hepatic
ducts and portal veins.
PMID- 28411348
TI - Quantitative detection of fecal contamination with domestic poultry feces in
environments in China.
AB - Poultry are an important source of fecal contamination in environments. However,
tools for detecting and tracking this fecal contamination are in the early stages
of development. In practice, we have found that source tracking methods targeting
the 16S rRNA genes of poultry-specific microbiota are not sufficiently sensitive.
We therefore developed two quantitative PCR assays for detection of poultry fecal
contamination, by targeting chicken and duck mitochondrial genes: NADH
dehydrogenase subunit 5 (ND5) and cytochrome b (cytb). The sensitivity of both
assays was 100% when tested on 50 chicken and duck fecal samples from 10
provinces of China. These assays were also tested in field samples, including
soil and water collected adjacent to duck farms, and soils fertilized with
chicken manure. Poultry mitochondrial DNA was detected in most of these samples,
indicating that the assays are a robust method for monitoring environmental
contamination with poultry feces. Complemented with existing indicators of fecal
contamination, these markers should improve the efficiency and accuracy of
microbial source tracking.
PMID- 28411346
TI - Peroral endoscopic myotomy compared with pneumatic dilation for newly diagnosed
achalasia.
AB - BACKGROUND: This study retrospectively compared the safety and efficacy of two
endoscopic techniques for treating newly diagnosed achalasia, pneumatic dilation
(PD), and peroral endoscopic myotomy (POEM). METHODS: Demographics, clinical and
manometric data, and outcomes were collected from the medical records of patients
who received POEM or PD as the primary therapy for achalasia at our hospital from
January 2012 to August 2015. RESULTS: Of 72 patients, 32 and 40 received POEM and
PD, respectively. The two groups had similar preoperative features. On short-term
follow-up, improvements in high-resolution esophageal manometry and barium
esophagogram parameters were similar. For PD, the success rates at 3, 6, 12, 24,
and 36 months were 95, 88, 75, 72, and 60%, respectively. For POEM, these were
96, 96, 96, 93, and 93% (P = 0.013, log-rank test). On subgroup analysis, the
success rate was higher with POEM than that with PD in all 3 manometric subtypes,
but only that of type III was statistically significant. POEM required
significantly longer operative time and hospitalization than did PD (P < 0.001).
Four POEM patients experienced subcutaneous emphysema. The rate of
gastroesophageal reflux was higher in patients treated by POEM (18.8%) than that
in PD (10%; P = 0.286). CONCLUSIONS: In the intermediate term, the remission rate
of symptoms associated with POEM therapy was better than that with PD for newly
diagnosed achalasia, especially in patients with type III achalasia. The short
term outcomes of the two therapies were similar.
PMID- 28411349
TI - Effect of low appendicular lean mass, grip strength, and gait speed on the
functional outcome after surgery for distal radius fractures.
AB - : Patients with low appendicular lean mass plus slow gait speed or weak grip
strength are at risk for poor functional recovery after surgery for distal radius
fracture, even when they have similar radiologic outcomes. INTRODUCTION: Loss of
skeletal muscle mass and consequent loss in muscle function associate with aging,
and this condition negatively impacts the activities of daily living and
increases elderly individuals' frailty to falls. Thus, patients with low
appendicular lean mass would show different functional recovery compared to those
without this condition after surgery for distal radius fracture (DRF). This study
compares the functional outcomes after surgery for DRF in patients with or
without low appendicular lean mass plus slowness or weakness. METHODS: A total of
157 patients older than 50 years of age with a DRF treated via volar plate
fixation were enrolled in this prospective study. A definition of low
appendicular lean mass with slowness or weakness was based on the consensus of
the Asian Working Group for Sarcopenia. The researchers compared functional
assessments (wrist range of motion and Michigan Hand Questionnaire [MHQ]) and
radiographic assessments (radial inclination, volar tilt, ulnar variance, and
articular congruity) 12 months after surgery between patients with and without
low appendicular lean mass plus slowness or weakness. Multivariable regression
analyses were performed to determine whether appendicular lean mass, grip
strength, gait speed, patient demographic, or injury characteristics accounted
for the functional outcomes. RESULTS: Patients with low appendicular lean mass
plus slowness or weakness showed a significantly lower recovery of MHQ score than
those in the control group throughout 12 months. There was no significant
difference in the range of motion between the groups. The radiologic outcomes
showed no significant difference between groups in terms of volar tilt, radial
inclination, or ulnar variance. According to multivariable regression analysis,
the poor recovery of MHQ score was associated with an increase in age, weak grip
strength, and lower appendicular lean mass, and these three factors accounted for
37% of the variation in the MHQ scores. CONCLUSION: Patients with low
appendicular lean mass plus slowness or weakness are at risk for poor functional
recovery after surgery for DRF, even when they have similar radiologic outcomes.
PMID- 28411350
TI - Acute Appendicitis, Somatosensory Disturbances ("Head Zones"), and the
Differential Diagnosis of Anterior Cutaneous Nerve Entrapment Syndrome (ACNES).
AB - BACKGROUND: Anterior cutaneous nerve entrapment syndrome (ACNES) is a neuropathic
abdominal wall pain syndrome typically characterized by locally altered skin
sensations. On the other hand, visceral disease may also be associated with
similar painful and altered skin sensations ("Head zones"). Aim of the study was
to determine if patients with acute appendicitis demonstrated somatosensory
disturbances in the corresponding right lower quadrant Head zone. METHODS: The
presence of somatosensory disturbances such as hyperalgesia, hypoesthesia,
altered cool perception, or positive pinch test was determined in 100 patients
before and after an appendectomy. Potential associations between altered skin
sensations and various items including age, sex, history, body temperature, C
reactive protein (CRP), leukocyte count, and type of appendicopathy (normal,
inflamed, necrotic, or perforated) were assessed. RESULTS: A total of 39 patients
demonstrated at least one right lower abdominal quadrant skin somatosensory
disturbance before the laparoscopic appendectomy. However, locoregional skin
sensation normalized in all but 2 patients 2 weeks postoperatively. No
differences were found concerning patient characteristics or type of
appendicopathy between populations with or without altered lower abdominal skin
sensations. CONCLUSION: A substantial portion of patients with acute appendicitis
demonstrate right lower abdominal somatosensory disturbances that are similar as
observed in acute ACNES. Both may be different sides of the same coin and are
possibly expressions of segmental phenomena as described by Head. McBurney's
point, a landmark area of maximum pain in acute appendicitis, is possibly a
trigger point within a Head zone. Differentiating acute appendicitis from acute
ACNES is extremely difficult, but imaging and observation may aid in the
diagnostic process.
PMID- 28411351
TI - Simultaneous Resection for Synchronous Colorectal Liver Metastasis: the New
Standard of Care?
AB - BACKGROUND: Optimal surgical management for patients with synchronous colorectal
cancer liver metastasis is controversial. We provide an analysis of surgical
utilization and outcomes for patients presenting with synchronous colon and
rectal cancer liver metastasis between simultaneous and staged approaches.
METHODS: SPARCS database was used to follow patients undergoing surgery for
colorectal cancer with liver metastases from 2005 to 2014. Using International
Classification of Diseases, Ninth Revision codes, we identified patients
undergoing staged and simultaneous resection. Our primary endpoint was major
events at 30-day follow-up. RESULTS: Of the patients, 1430 underwent surgery for
synchronous colorectal primary and liver metastases between 2005 and 2014. There
was no difference in adjusted rates of major events or anastomotic leak. Patients
undergoing simultaneous resection were significantly less likely to experience
prolonged length of stay (OR = 0.28; 95% CI = 0.21-0.37) or high hospital charges
(OR = 0.24; 95% CI = 0.17-0.32) compared to staged resection even among patients
undergoing total hepatic lobectomy and complex colorectal resection. CONCLUSIONS:
Simultaneous resection was found to be equally as safe as staged resection even
when evaluating patients undergoing more complex operations, and led to lower
health care utilization. Under appropriate clinical circumstances, simultaneous
resection offers benefits to patients and the health care system and should be
the recommended surgical approach.
PMID- 28411352
TI - Impact of postoperative complications on readmission and long-term survival in
patients following surgery for colorectal cancer.
AB - PURPOSE: It is well known that specific postoperative complications such as
stroke influence readmissions and overall survival (OS) after surgery for
colorectal cancer (CRC). Whether overall hospital morbidity is associated with
increased risk of readmission and poorer long-term survival is unknown. New tools
are available to accurately quantify overall morbidity, such as the comprehensive
complication index (CCI). The aim is to evaluate the impact of complications on
readmission and overall survival (OS) in patients operated for colorectal cancer.
METHODS: Postoperative complications of patients undergoing surgery for CRC were
assessed over a 5-year period using the Clavien-Dindo classification, and overall
morbidity was assessed by using the CCI. Individual scores were analyzed
regarding their association with readmission and OS by using the multivariate
logistic and Cox proportional-hazards regression analysis, respectively. RESULTS:
Two hundred eighty-four patients were operated for CRC, of which 22 (8%) were
readmitted. One hundred five patients (37%) developed at least one postoperative
complication during the hospital stay. While single complications or the use of
severe complication only (grade >=IIIb) was not associated with readmission,
overall morbidity (CCI) predicted readmission (OR 1.02 (95% CI 1.0-1.04), p =
0.044). Similarly, morbidity assessed by the CCI had a significant negative
predictive value on OS, e.g., patients with a CCI of 20 were 22% more likely to
die within a 5-year follow-up, when compared to patients with a CCI of 10 (p =
0.022). CONCLUSIONS: Overall combined morbidity as assessed by the CCI leads to
more frequent readmission, and is associated with poorer long-term survival after
surgery for CRC.
PMID- 28411353
TI - Prevalence of Body Dysmorphic Disorder in Plastic Surgery and Dermatology
Patients: A Systematic Review with Meta-Analysis.
AB - : The aim of the present study was to evaluate the prevalence of body dysmorphic
disorder in plastic surgery and dermatology patients, by performing a systematic
review of the literature and meta-analysis. The most relevant studies published
originally in any language were analyzed. The literature search was performed
using the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and
Scielo databases. The final sample comprised 33 publications that were submitted
to meta-analysis. The study verified that 15.04% of plastic surgery patients had
body dysmorphic disorder (range 2.21-56.67%); patient mean age was 34.54 +/-
12.41 years, and most were women (74.38%). Among dermatology patients, 12.65%
(range 4.52-35.16%) had body dysmorphic disorder; patient mean age was 27.79 +/-
9.03 years, and most were women (76.09%). Both plastic surgeons and
dermatologists must adequately assess their patients to identify those with a
higher likelihood of body dysmorphic disorder and should arrange
multidisciplinary care for such individuals. LEVEL OF EVIDENCE V: This journal
requires that authors assign a level of evidence to each article. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 28411355
TI - Rabies Acquired Through Kidney Transplantation in a Child: A Case Report.
AB - Rabies is usually transmitted to humans through bites of infected animals;
however, it can rarely be transmitted through deceased donor organs or tissues
when not suspected. Here, we report a case of rabies transmission in a child. The
child was a 5-year-old girl who was admitted to the pediatric intensive care unit
with encephalitis of unexplained cause 3.5 months after she received a kidney
transplant from a deceased donor. The laboratory and imaging studies did not
reveal any explanation for her rapidly declining clinical and neurologic
condition, which ended with death 4 days after admission. Death of another
recipient from the same donor led to an investigation that revealed rabies as the
cause. Both corneas were explanted from other recipients to prevent further
death. Polymerase chain reaction sequence analysis of the corneas was consistent
with a rabies virus from the same donor's state of residence. Rabies
transmission, although rare, should be suspected when a donor comes from or has
visited endemic countries. Donors with unclear causes of death should be
rejected.
PMID- 28411354
TI - Preventing the Complications Associated with the Use of Dermal Fillers in Facial
Aesthetic Procedures: An Expert Group Consensus Report.
AB - BACKGROUND: The use of dermal fillers in minimally invasive facial aesthetic
procedures has become increasingly popular of late, yet as the indications and
the number of procedures performed increase, the number of complications is also
likely to increase. Paying special attention to specific patient characteristics
and to the technique used can do much to avoid these complications. Indeed, a
well-trained physician can also minimize the impact of such problems when they do
occur. METHODS: A multidisciplinary group of experts in aesthetic treatments
reviewed the main factors associated with the complications that arise when using
dermal fillers. A search of English, French and Spanish language articles in
PubMed was performed using the terms "complications" OR "soft filler
complications" OR "injectable complications" AND "dermal fillers". An initial
document was drafted that reflected the complications identified and
recommendations as to how they should be handled. This document was then reviewed
and modified by the expert panel, until a final text was agreed upon and
validated. RESULTS: The panel addressed consensus recommendations about the
preparation, the procedure and the post-procedural care. The panel considered it
crucial to obtain an accurate medical history to prevent potential complications.
An additional clinical assessment, including standardized photography, is also
crucial to evaluate the outcomes and prevent potential complications.
Furthermore, the state of the operating theatre, the patient's health status and
the preparation of the skin are critical to prevent superficial soft tissue
infections. Finally, selecting the appropriate technique, based on the
physician's experience, as well as the characteristics of the patient and filler,
helps to ensure successful outcomes and limits the complications. CONCLUSIONS:
This consensus document provides key elements to help clinicians who are starting
to use dermal fillers to employ standard procedures and to understand how best to
prevent potential complications of the treatment. LEVEL OF EVIDENCE V: This
journal requires that authors assign a level of evidence to each article. For a
full description of these Evidence-Based Medicine ratings, please refer to the
Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 28411356
TI - Mitochondrial Neurogastrointestinal Encephalomyopathy Syndrome Treated with Stem
Cell Transplant: A Case Series and Literature Review.
AB - Mitochondrial neurogastrointestinal encephalomyopathy syndrome is a rare
autosomal recessive multisystem disorder caused by nuclear TYMP gene mutations,
which leads to deficiency in thymidine phosphorylase enzyme. This deficiency then
leads to mitochondrial dysfunction, which causes the features characteristic of
this syndrome, including severe muscle wasting, gastrointestinal dysmotility,
leukoencephalopathy, peripheral neuropathy, and ophthalmoplegia. Here, we present
a case series of 3 patients with mitochondrial neurogastrointestinal
encephalomyopathy from Saudi Arabia who underwent allogeneic stem cell transplant
at King Faisal Specialist Hospital (Riyadh, Saudi Arabia). Two patients died
within the first year of transplant, and the third is still alive but without
improvement in clinical features. Allogeneic hematopoietic stem cell transplant
related mortality appears to be high; this may at least be partially related to
established end-organ effects with decreased performance status. Although
allogeneic hematopoietic stem cell transplant clearly affects correction of
genetic and biochemical defects in mitochondrial neurogastrointestinal
encephalomyopathy, its ability to reverse or improve established clinical
manifestations has not been proven.
PMID- 28411357
TI - Kidney Transplant From a Deceased Donor With Renal Artery Aneurysm: A Case
Report.
AB - The use of marginal kidneys or kidneys with pathologic problems (such as renal
artery aneurysms in a living or deceased donor) is on the rise due to organ
shortages and improvements in surgical techniques. When renal vascular
abnormalities are detected during a transplant, it puts the surgeon in a
difficult position to decide what to do with the organ. In this study, we report
a case of a kidney from a deceased donor who had 2 renal artery saccular
aneurysms, which we were able to use for transplant. The recipient was a 61-year
old male patient with diabetic nephropathy and significant comorbidities. Kidney
transplant was performed successfully with a good outcome. Recent advancements in
surgical techniques have allowed the use of kidneys with renal artery aneurysms
for kidney transplant, thus helping to overcome shortages of transplantable
organs.
PMID- 28411358
TI - Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic
Hematopoietic Stem Cell Transplant Recipients.
AB - OBJECTIVES: Acute kidney injury is a relatively frequent complication of
allogenic hematopoietic stem cell transplant, resulting in increased risk of
morbidity and mortality. Early diagnosis and management of acute kidney injury is
of great importance for prevention of poor outcomes in these transplant
recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for
allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation
Unit of Gazi University Faculty of Medicine, were included in this prospective
study. Serial measurements of serum creatinine and creatinine clearance were
obtained before administration of conditioning regimen and at 0, 7, 14, 21, and
28 days after start of conditioning. Blood and urine samples were also obtained
for the measurement of serum cystatin C and urine neutrophil gelatinase
associated lipocalin levels before conditioning and 24 hours before each serum
creatinine measurement. RESULTS: During the median 25 days of follow-up, acute
kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2,
and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury
Network classification. There were significant positive correlations between
serum cystatin C levels and serum creatinine levels and negative correlations
with creatinine clearance levels at each time point (P < .001), whereas no
statistically significant associations were observed with urinary neutrophil
gelatinase-associated lipocalin levels. Both univariate and multivariate Cox
regression models showed a statistically significant association between serum
cystatin C levels and development of acute kidney injury, whereas urine
neutrophil gelatinase-associated lipocalin levels did not show any significant
associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for
early detection of acute kidney injury in adult allogenic hematopoietic stem cell
transplant recipients. Close monitoring of kidney function by sensitive
biomarkers might provide early recognition and timely management of acute kidney
injury in high-risk patient populations.
PMID- 28411359
TI - Incidence and Treatment of Bile Stones After Liver Transplant.
AB - OBJECTIVES: Although the incidence of bile stones after liver transplant is rare
(2%-6%), various complications can occur, including recurrent cholangitis,
biliary strictures, graft loss, and patient mortality. MATERIALS AND METHODS: We
retrospectively evaluated bile stone incidence, pathogenesis, and treatment in
352 liver transplant recipients, comparing demographics, transplant indication,
blood lipid profile, bile reconstruction technique, postoperative complications,
time of diagnosis, and treatment regimens. RESULTS: Of 352 recipients, 18 had
bile stones, with 13 of these patients (72.2%) receiving duct-to-duct bile
reconstruction, 17 having biliary complications before bile stone development, 7
(38.9%) having biliary stricture, 6 (33.3%) having biliary leakage, 4 (22.2%)
having biliary strictures secondary to biliary leakage, and 7 (38.9%) having
hepatic artery complications early posttransplant. Previous biliary complications
and recurrent cholangitis significantly increased bile stones. Incidence in
patients with triglyceride levels > 250 mg/dL was significantly different from
those with levels at < 250 mg/dL. Cold ischemia time was significant in those
with and without bile stones (P = .001). Three patients (16%) were treated by
endoscopic tools, with others (15/18, 84%) treated via percutaneous procedures.
CONCLUSIONS: Bile stone risk can be greater in those with previous biliary
complications, hepatic artery problems, long cold ischemia time, and high
cholesterol levels. It can be successfully treated by endoscopic and percutaneous
techniques.
PMID- 28411360
TI - Association Between TLR2, TLR4, and CD14 Gene Polymorphisms and Acute Rejection
in Kidney Transplant.
AB - OBJECTIVES: Toll-like receptors play an important role in innate and adaptive
immune responses and can induce acute graft rejection, especially in the early
phase after transplant. The aim of this study was to evaluate the possible
association between TLR2, TLR4, and CD14 polymorphisms and acute renal rejection.
MATERIALS AND METHODS: Our study included 239 patients seen between 2013 and
2015. Patients were classified into 3 groups: acute rejection group (71
patients), stable graft function group (71 patients), and healthy control group
(97 patients). Polymorphisms in TLR2 (Arg753Gln, rs5743708), TLR4 (Asp299Gly,
rs4986790; Thr399Ile, rs4986791), and CD14 (-159C/T, rs2569190) were determined
by the TaqMan allelic discrimination assay for detection of single-nucleotide
polymorphisms. RESULTS: The genotype distribution of CD14 rs2569190C/T was found
to be significantly different among the acute rejection, stable graft function,
and healthy control groups (P < .05). Interestingly, based on logistic
regression, CD14 genotype (rs2569190) in patients with acute rejection was still
significant after including risk factors. The adjusted odds ratio for CD14 CT+TT
over CC genotype was calculated as 3.172 (95% confidence interval, 1.397-7.200; P
= .006). Moreover, incidence of acute rejection and graft loss were significantly
more frequent in recipients carrying CD14 TT (95% confidence interval, 2.81
27.16; P <= .001). In contrast to CD14, no significant differences were observed
in the single-nucleotide polymorphisms of TLR2 and TLR4 genes in the acute
rejection group versus the stable graft function and healthy control groups. The
presence of CD14 T allele was associated with a significantly lower rejection
free survival compared with the CD14 CT and CC genotypes (P <= .001).
CONCLUSIONS: Renal transplant recipients carrying the CD14-159 TT genotype have
significantly higher risk of acute rejection and reduced transplant survival rate
than patients with heterozygous or wild-type genotypes.
PMID- 28411361
TI - Liver Transplant in Children with Hepatoblastoma.
AB - OBJECTIVES: In this paper, the results of liver transplant due to hepatoblastoma
in 10 pediatric patients at Istanbul Sisli Memorial Hospital Transplantation
Center are presented. MATERIALS AND METHODS: We retrospectively evaluated medical
records of pediatric patients diagnosed with hepatoblastoma and who underwent
liver transplant at our clinic between January 2009 and March 2014. We examined
age, weight, chemotherapy regimen, graft type for liver transplant, duration of
hospital stay, complications, follow-up duration, and survival information.
RESULTS: The median age of the 10 patients included in our study was 13.5 months
(range, 8-120 mo), and the median weight was 10 kg (range, 6.5-30 kg). Two of the
patients were twins. Five patients had pretreatment extent of disease III
(centrally placed cases), and five had pretreatment extent of disease IV
hepatoblastoma. Preoperative chemotherapy was given to 7 patients as cisplatin
plus doxorubicin and to 3 patients per the International Childhood Liver Tumors
Strategy Group 3 High-Risk Protocol at external centers. These protocols were
administered according to treatment center preference. Nine patients received
transplants from living donors. Two grafts were right lobes, and 7 were left
lateral segments. In the remaining patient, a whole liver was received from a
deceased donor. The histopathologic subgroups were epithelial in 5 patients, with
others being of mixed type. Postoperative complications occurred in 3 patients as
infection, intra-abdominal fluid collection, and acute rejection. The median
follow-up was 32 months. One patient died because of lung metastasis within 9
months after transplant. CONCLUSIONS: Centers should offer liver transplant to
patients with centrally located tumors. For centers that have an insufficient
number of deceased donors, living-donor liver transplant with optimal planning
and early treatment can be performed.
PMID- 28411362
TI - Knockdown of Long Noncoding RNA TUG1 Inhibits the Proliferation and Cellular
Invasion of Osteosarcoma Cells by Sponging miR-153.
AB - Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been confirmed
to be involved in the progression of various cancers; however, its mechanism of
action in osteosarcoma has not been well addressed. In our study, TUG1 was
overexpressed and miR-153 was downregulated in osteosarcoma tissues and cell
lines. A loss-of-function assay showed that TUG1 knockdown suppressed the
viability, colony formation, and invasion of osteosarcoma cells in vitro.
Moreover, TUG1 was confirmed to be an miR-153 sponge. Ectopic expression of TUG1
reversed the inhibitory effect of miR-153 on the proliferation and invasion of
osteosarcoma cells. Further transplantation experiments proved the carcinogenesis
of TUG1 in osteosarcoma in vivo. Collectively, our study elucidated that TUG1
contributes to the development of osteosarcoma by sponging miR-153. These
findings may provide a novel lncRNA-targeted therapy for patients with
osteosarcoma.
PMID- 28411363
TI - Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance.
AB - Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide,
comprises a range of disorders including simple steatosis, steatohepatitis,
cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal
models for the study of ALD pathogenesis have been developed. Recently, a chronic
plus-binge ethanol feeding model was reported. This model induces significant
steatosis, hepatic neutrophil infiltration, and liver injury. A clinically
relevant model of high-fat diet feeding plus binge ethanol was also developed,
which highlights the risk of excessive binge drinking in obese/overweight
individuals. All of these models recapitulate some features of the different
stages of ALD and have been widely used by many investigators to study the
pathogenesis of ALD and to test for therapeutic drugs/components. However, these
models are somewhat variable, depending on mouse genetic background, ethanol
dose, and animal facility environment. This review focuses on these models and
discusses these variations and some methods to improve the feeding protocol. The
pathogenesis, clinical relevance, and translational studies of these models are
also discussed.
PMID- 28411365
TI - Analysis of glycosylated flavonoids extracted from sweet-cherry stems, as
antibacterial agents against pathogenic Escherichia coli isolates.
AB - The aim of this study was to evaluate the bioactivity of flavonoids extracted
from sweet-cherry stems which are often used by a traditional system of medicine
to treat gastro-intestinal and urinary tract infections but lacking any
consistent scientific evidence; moreover the information about the class of
phenolics, their content and the potential bioactivity of such material is very
scarce. Thus, in this context, we have set a research study in which we evaluated
the profile and content of phenolics extracted from sweet-cherry stems through a
conventional (70oC and 20 min) and ultrasound assisted extraction (40 kHz, room
temperature and 20 min). The extracts were phytochemically characterized by using
an HPLC-DAD-UV/VIS system and assayed by an in vitro minimum inhibitory
concentration (MIC) bioassay against Escherichia coli isolates. Simultaneously,
the total antioxidant activities were measured using the 2,2'-azinobis-3
ethylbenzothiazoline-6-sulphonate (ABTS*+) radical cation assay. Our results
indicate that sweet-cherry stems have a high content of sakuranetin, ferulic
acid, p-coumaric acid, p-coumaroylquinic acid, chlorogenic acid and its isomer
neochlorogenic acid. Their average levels were highly affected by the extraction
method used (p<0.001). The same trend was observed for total antioxidant activity
and MIC values. The extracts produced with ultrasounds presented both, a higher
total antioxidant activity and a lower minimum inhibitory concentration.
Statistical analyses of our results showed a significant correlation (p<0.01) of
total antioxidant activity and minimum inhibitory concentration with phenolics
present in the extracts studied. Thus, we can conclude that cherry stems can be
further exploited to purify compounds and produce coproducts with enhanced
biologically added value for pharmaceutical industry.
PMID- 28411364
TI - Centriolar remodeling underlies basal body maturation during ciliogenesis in
Caenorhabditis elegans.
AB - The primary cilium is nucleated by the mother centriole-derived basal body (BB)
via as yet poorly characterized mechanisms. BBs have been reported to degenerate
following ciliogenesis in the C. elegans embryo, although neither BB architecture
nor early ciliogenesis steps have been described in this organism. In a previous
study (Doroquez et al., 2014), we described the three-dimensional morphologies of
sensory neuron cilia in adult C. elegans hermaphrodites at high resolution. Here,
we use serial section electron microscopy and tomography of staged C. elegans
embryos to demonstrate that BBs remodel to support ciliogenesis in a subset of
sensory neurons. We show that centriolar singlet microtubules are converted into
BB doublets which subsequently grow asynchronously to template the ciliary
axoneme, visualize degeneration of the centriole core, and define the
developmental stage at which the transition zone is established. Our work
provides a framework for future investigations into the mechanisms underlying BB
remodeling.
PMID- 28411366
TI - Anticancer activity of some polyamine derivatives on human prostate and breast
cancer cell lines.
AB - The aim of this study was to expand our knowledge about anticancer activity of
some polyamine derivatives with quinoline or chromane as terminal moieties.
Tested compounds were evaluated in vitro towards metastatic human prostate
adenocarcinoma (PC3), human carcinoma (DU145) and mammary gland adenocarcinoma
(MCF7) cell lines. Cell viability was estimated on the basis of mitochondrial
metabolic activity using water-soluble tetrazolium WST1 to establish effective
concentrations of the tested compounds under experimental conditions. Cytotoxic
potential of polyamine derivatives was determined by the measurement of lactate
dehydrogenase activity released from damaged cells, changes in mitochondrial
membrane potential, the cell cycle distribution analysis and apoptosis assay. It
was revealed that the tested polyamine derivatives differed markedly in their
antiproliferative activity. Bischromane derivative 5a exhibited a rather
cytostatic than cytotoxic effect on the tested cells, whereas quinoline
derivative 3a caused changes in cell membrane integrity, inhibited cell cycle
progression, as well as induced apoptosis of prostate and breast cancer cells
which suggest its potential application in cancer therapy.
PMID- 28411368
TI - Laparoscopy-specific ventral approach in laparoscopic hemihepatectomy.
AB - BACKGROUND: The laparoscopic caudal approach is very different from the open
ventral approach, specifically with respect to the surgical view, which is
completely different and is the underlying reason for why laparoscopic
hepatectomy is technically challenging. We have introduced a new laparoscopy
specific ventral approach in laparoscopic hemihepatectomy. METHODS: The liver was
transected from the ventral side to the dorsal side, via a flexible laparoscope,
as in open liver resection. The key characteristic of the ventral approach is the
early opening of the cranial part, which guides the accurate transection and
maintains an open cutting plane. The middle hepatic vein is exposed from the root
side toward the periphery. RESULTS: From March to December 2016, this technique
was performed on 12 patients. Of these patients, five underwent right
hepatectomy, five underwent left hepatectomy, and two underwent extended left
hepatectomy that included the middle hepatic vein. The median operative time was
250 min (range 210-350 min), and the median blood loss was 165 mL (range 100-260
mL). There was no postoperative morbidity or mortality. The median postoperative
hospital stay was 8 days (range 5-14 days). CONCLUSION: This ventral approach may
be an effective and feasible technique for laparoscopic hemihepatectomy.
PMID- 28411367
TI - Serum 25(OH)D concentration, common variants of the VDR gene and lung cancer
occurrence.
AB - The first aim of our study was to examine the association between common variants
in VDR [rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI) and
rs11568820 (Cdx2)] and lung cancer risk in the Polish population. Genotyping and
statistical analysis which included Chi-square test with Yates correction and
haplotype frequency analysis were performed on a series of 840 consecutively
collected lung cancer patients and 920 healthy controls. The second aim was to
evaluate the link between serum 25(OH)D concentration and the number of lung
cancers in a subgroup of 200 patients. A separate control group that consisted of
400 matched (by age, sex, smoking habits and the season of blood collection)
healthy individuals was used to avoid posterior adjustment on the matched
variables. Statistical analysis with the use of Chi-square test with Yates was
performed. We found no statistically significant difference in the distribution
of the allels of studied VDR variants among cases and controls. A statistically
significant over-representation of VDR haplotypes: rs731236_A + rs1544410_T [odds
ratio (OR) = 2.43, 95% confidence interval (CI) = 1.11-5.32, p < 0.001],
rs731236_G + rs1544410_T (OR = 1.54, 95% CI = 1.31-1.81, p < 0.001) and
rs731236_G + rs1544410_C (OR = 0.04, 95% CI = 0.03-0.07, p < 0.001) was detected.
We found a tendency toward an increased number of lung cancers among individuals
with low serum levels of 25(OH)D. To answer the question, whether VDR can be
regarded as lung cancer susceptibility gene and low 25(OH)D serum levels is
associated with lung cancer occurrences, additional, multicenter study needs to
be performed.
PMID- 28411369
TI - Comparison of equine platelet function and survival in whole blood collected in
acid-citrate-dextrose solution or citrate-phosphate-dextrose-adenine solution.
AB - BACKGROUND: Equine whole blood collection and storage methods have been evaluated
to assess red blood cell viability; however, platelet (PLT) viability has not
been comprehensively assessed. OBJECTIVES: The purpose of the study was to
compare viability of PLTs collected in whole blood into 2 different
anticoagulants. METHODS: Whole blood from 6 healthy adult Thoroughbred horses was
collected into citrate-phosphate-dextrose-adenine (CPDA) or acid-citrate-dextrose
(ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon
dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured
within 10 minutes of collection and then again one hour later at which time PLT
aggregometry was performed to assess PLT function. RESULTS: Aggregometry mean
amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH,
bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA
compared to ACD. Lactate concentration was higher following one hour in either
anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were
significantly higher in ACD compared to CPDA at collection. CONCLUSIONS: Platelet
aggregometry results suggest that CPDA is superior to ACD for maintaining PLT
viability following whole blood collection. This may be associated with the
higher, more neutral pH as well as an increase in glucose available for
metabolism. Although lactate was increased in the CPDA samples it was not high
enough to decrease pH and therefore may not have been high enough to cause
morphologic lesions and loss of PLT viability.
PMID- 28411370
TI - Nomograms to estimate long-term overall survival and tongue cancer-specific
survival of patients with tongue squamous cell carcinoma.
AB - The aim of this study was to construct nomograms to predict long-term overall
survival (OS) and tongue cancer-specific survival (TCSS) of tongue squamous cell
carcinoma (TSCC) patients based on clinical and tumor characteristics. Clinical,
tumor, and treatment characteristics of 12,674 patients diagnosed with TSCC
between 2004 and 2013 were collected from the Surveillance, Epidemiology, and End
Results database. These patients were then divided into surgery and nonsurgery
cohorts, and nomograms were developed for each of these groups. The step-down
method and cumulative incidence function were used for model selection to
determine the significant prognostic factors associated with OS and TCSS. These
prognostic variables were incorporated into nomograms. An external cohort was
used to validate the surgery nomograms. Seven variables were used to create the
surgery nomograms for OS and TCSS, which had c-indexes of 0.709 and 0.728,
respectively; for the external validation cohort, the c-indexes were 0.691 and
0.711, respectively. Nine variables were used to create the nonsurgery nomograms
for OS and TCSS, which had c-indexes of 0.750 and 0.754, respectively. The
calibration curves of the 5- and 8-year surgery and nonsurgery nomograms showed
excellent agreement between the probabilities and observed values. By
incorporating clinicopathological and host characteristics in patients, we are
the first to establish nomograms that accurately predict prognosis for individual
patients with TSCC. These nomograms ought to provide more personalized and
reliable prognostic information, and improve clinical decision-making for TSCC
patients.
PMID- 28411371
TI - "Cough Hemicrania" - An Overlapping Form of Headache: Case Reports.
AB - OBJECTIVE: To describe two patients with recurring unilateral brief headaches
that fulfilled criteria for both primary cough headache (CH) and chronic
paroxysmal hemicrania (CPH). BACKGROUND: CH is typically a bilateral headache,
specifically triggered by cough, straining, or other Valsalva maneuvers. The
report of cases sharing features with other primary headache disorders, such as
CPH, suggest common pathogenic mechanisms. METHODS: Case reports. RESULTS: Two
patients (one man), aged 55 and 64, had a two-year history of daily, unilateral,
side-locked headache attacks, lasting about 15 minutes, and associated with
ipsilateral tearing. Headaches were triggered by cough, sneezing, laughing, or
bending forward. Both patients experienced a marked and sustained improvement
with indomethacin, and both relapsed when it was interrupted. CONCLUSIONS: These
cases suggest the existence of transitional phenotypes, or shared pathogenic
mechanisms, between CH and CPH, two indomethacin-responsive headaches. A more
comprehensive analysis of different CH subtypes is necessary to understand their
relation with other primary headaches.
PMID- 28411372
TI - Development of a Vivid FRET System Based on a Highly Emissive dG-dC Analogue
Pair.
AB - A new type of Forster Resonance Energy Transfer (FRET) system using highly
emissive isomorphic nucleobase analogues is reported. The FRET pair consists of 2
aminothieno[3,4-d]pyrimidine G-mimic deoxyribonucleoside (th dG) as an energy
donor and 1,3-diaza-2-oxophenothiazine (tC) as an energy acceptor. The distance
and orientation between donor and acceptor was controlled by systematic
incorporation of th dG and tC into DNA sequences to investigate the FRET
efficiencies. This is the first Watson-Crick base-pairable FRET pair to produce
vivid colors. In addition, this nucleic acid-based FRET pair was used to monitor
DNA conformation and achieved visualization of the B-Z transition.
PMID- 28411373
TI - Impact of major vascular resection on outcomes and survival in patients with
intrahepatic cholangiocarcinoma: A multi-institutional analysis.
AB - BACKGROUND: Major vascular involvement (IVC or portal vein) for intrahepatic
cholangiocarcinoma (ICC) has traditionally been considered a contraindication to
resection. We sought to define perioperative outcomes and survival of ICC
patients undergoing hepatectomy with major vascular resection in a large
international multi-institutional database. METHODS: A total of 1087 ICC patients
who underwent curative-intent hepatectomy between 1990 and 2016 were identified
from 13 institutions. Multivariable logistic and cox regressions were used to
determine the impact of major vascular resection on perioperative and survival
outcomes. RESULTS: Of 1087 patients who underwent resection, 128 (11.8%) also
underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV
resections, 9 [7.0%] combined resections). Despite more advanced disease, major
vascular resection was not associated with the risk of any complication (OR =
0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post
operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32
3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737,
95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40)
survival were similar among patients who did and did not undergo major vascular
resection (both P > 0.05). CONCLUSION: Among patients with ICC, major vascular
resection was not associated with worse perioperative or oncologic outcomes.
Concurrent major vascular resection should be considered in appropriately
selected patients with ICC undergoing hepatectomy.
PMID- 28411374
TI - Magnetic Response of Aromatic Rings Under Rotation: Aromatic Shielding Cone of
Benzene Upon Different Orientations of the Magnetic Field.
AB - The induced shielding cone is one of the most characteristic aspects of aromatic
species. Herein, we explore its behavior under different orientations of the
applied magnetic field by evaluating the overall and dissected pi- and sigma
electron contributions. Our results shed light onto the orientation dependence
behavior of the shielding cone, unraveling a characteristic pattern upon rotation
of the aromatic ring. This pattern decreases the long range of the magnetic
response, such that it resembles the behavior under constant molecular tumbling
in solution.
PMID- 28411375
TI - Development of Tetramethylenedisulfotetramine (TETS) Hapten Library: Synthesis,
Electrophysiological Studies, and Immune Response in Rabbits.
AB - There is a need for fast detection methods for the banned rodenticide
tetramethylenedisulfotetramine (TETS), a highly potent blocker of the gamma
aminobutyric acid (GABAA ) receptors. General synthetic approach toward two
groups of analogues was developed. Screening of the resulting library of
compounds by FLIPR or whole-cell voltage-clamp revealed that, despite the
structural differences, some of the TETS analogues retained GABAA receptor
inhibition; however, their potency was an order of magnitude lower. Antibodies
raised in rabbits against some of the TETS analogues conjugated to protein
recognized free TETS and will be used for the development of an immunoassay for
TETS.
PMID- 28411376
TI - Nodular oncocytic hyperplasia: Can cytomorphology allow for the preoperative
diagnosis of a nonneoplastic salivary disease?
AB - BACKGROUND: Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is
a benign process that does not inherently require surgical excision. However,
cytologic findings in fine-needle aspiration (FNA) of oncocytosis cases have not
been well characterized previously, limiting preoperative identification.
METHODS: All available cases of oncocytosis with corresponding FNA specimens were
identified from the pathology archives of 3 academic institutions. Clinical,
cytologic, and histologic findings were tabulated for all cases. RESULTS: Twelve
cases of oncocytosis were identified from 11 patients, including 11 parotid FNA
specimens and 1 submandibular FNA specimen. On the original diagnoses, 6
specimens were classified as benign, 4 as atypical, and 2 as nondiagnostic.
Oncocytosis was listed in the differential diagnosis in only 1 case. Among
diagnostic aspirates, 8 demonstrated low cellularity and 2 demonstrated moderate
cellularity. All 10 cases demonstrated oncocytic cells in small to medium groups,
with single cells in just 1 case. Spindled and squamous morphology were each
noted in 3 cases. Four cases demonstrated cystic change and 1 showed background
mucin without goblet cells. No necrosis or mitoses were observed. CONCLUSIONS:
Although oncocytosis demonstrates some overlap with Warthin tumor and oncocytoma,
it lacks the diagnostic findings specific to oncocytic salivary gland
malignancies such as salivary duct carcinoma, acinic cell carcinoma, mammary
analog secretory carcinoma, and mucoepidermoid carcinoma. Despite current
limitations in the understanding of oncocytic salivary gland lesions, the
presence of a paucicellular specimen comprised of small groups of oncocytic cells
should raise the possibility of oncocytosis in the differential diagnosis and can
favor it in elderly patients with multiple salivary nodules. Cancer Cytopathol
2017;125:627-34. (c) 2017 American Cancer Society.
PMID- 28411379
TI - Ancillary testing strategies in salivary gland aspiration cytology: A practical
pattern-based approach.
AB - Fine needle aspiration of salivary gland tumors is a common preoperative triage
as it is useful in determining which patients should undergo surgical resection
and in guiding the extent of surgery in those cases deemed appropriate for
resection. While a specific diagnosis can be achieved on a cytologic specimen in
many cases, there is also a considerable amount of morphologic diversity that
prevents such confident preoperative classification and in these cases it can be
a challenge to confidently determine if a tumor is benign or malignant. Recently,
a pattern based risk stratification approach was proposed for salivary gland
cytology in which basaloid neoplasms are separated by stromal characteristics and
oncocytoid neoplasms are separated primarily by background material such as
mucus. In addition to potentially providing a stratification in risk of
malignancy for salivary gland tumors, this approach is also useful to narrow
differential diagnostic considerations and guide ancillary testing. In this
review we use this proposed pattern based approach as a framework to discuss
immunostains and fluorescence in situ hybridization studies which we find useful
in our practice.
PMID- 28411378
TI - Immune responses and long-term disease recurrence status after telomerase-based
dendritic cell immunotherapy in patients with acute myeloid leukemia.
AB - BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among
patients with high-risk acute myeloid leukemia (AML). In the current study, the
authors evaluated the feasibility, safety, immunogenicity, and therapeutic
potential of human telomerase reverse transcriptase (hTERT)-expressing autologous
dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were
produced from patient-specific leukapheresis, electroporated with an mRNA
encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A total of
22 patients with a median age of 58 years (range, 30-75 years) with intermediate
risk or high-risk AML in first or second complete remission (CR) were enrolled.
hTERT-DCs were generated for 24 patients (73%). A median of 17 intradermal
vaccinations (range, 6-32 intradermal vaccinations) containing 1*107 cells were
administered as 6 weekly injections followed by 6 biweekly injections. A total of
21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence)
received hTERT-DCs. RESULTS: hTERT-DCs were well tolerated with no severe
toxicities reported, with the exception of 1 patient who developed idiopathic
thrombocytopenic purpura. Of the 19 patients receiving hTERT-DCs in CR, 11
patients (58%) developed hTERT-specific T-cell responses that primarily were
targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)
binding affinities. With a median follow-up of 52 months, 58% of patients in CR
(11 of 19 patients) were free of disease recurrence at the time of their last
follow-up visit; 57% of the patients who were aged >=60 years (4 of 7 patients)
also were found to be free of disease recurrence at a median follow-up of 54
months. CONCLUSIONS: The generation of hTERT-DCs is feasible and vaccination with
hTERT-DCs appears to be safe and may be associated with favorable recurrence-free
survival. Cancer 2017;123:3061-72. (c) 2017 American Cancer Society.
PMID- 28411377
TI - miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol
by inhibiting MDR1 expression.
AB - MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R
gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of
cells, leading to decreased drug accumulation in cells and making cancer cells
susceptible to multidrug resistance. Here, we identified that miR-495 was
predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux
and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and
A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results
indicated that the expression of MDR1 in the above cells or tumours was
suppressed and that subsequently the drug accumulation in the MDR cells was
decreased, cell death was increased, and tumour growth was inhibited after
treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This
study suggests that pre-treatment with miR-495 before chemotherapy could improve
the curative effect on MDR1-based MDR cancer.
PMID- 28411380
TI - Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with
Decompensated Liver Cirrhosis.
AB - Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent
farnesoid X receptor agonist approved to treat cholestasis. We evaluated the
biodistribution and metabolism of OCA administered to carbon tetrachloride
induced cirrhotic rats. This was to ascertain if plasma and hepatic
concentrations of OCA are potentially more harmful than those of endogenous BAs.
After administration of OCA (30 mg/kg), we used liquid chromatography-mass
spectrometry to measure OCA, its metabolites, and BAs at different timepoints in
various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were
higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar
metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal
clearance were lower than in controls. BAs' qualitative and quantitative
compositions were not modified by a single administration of OCA. In all the
matrices studied, OCA concentrations were significantly lower than those of
endogenous BAs, potentially much more cytotoxic.
PMID- 28411381
TI - PBX3 is essential for leukemia stem cell maintenance in MLL-rearranged leukemia.
AB - Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system
transformation in MLL-rearranged (MLL-r) leukemia. Of these genes, HOXA9 has been
shown to be critical for leukemia cell survival, while MEIS1 has been identified
as an essential regulator for leukemia stem cell (LSC) maintenance. Although
significantly high expression of PBX3 was observed in clinical acute myeloid
leukemia (AML) samples, the individual role of PBX3 in leukemia development is
still largely unknown. In this study, we explored the specific role of PBX3 and
its associated regulatory network in leukemia progression. By analyzing the
clinical database, we found that the high expression of PBX3 is significantly
correlated with a poor prognosis in AML patients. ChIP-Seq/qPCR analysis in MLL-r
mouse models revealed aberrant epigenetic modifications with increased H3K79me2,
and decreased H3K9me3 and H3K27me3 levels in LSCs, which may account for the high
expression levels of Pbx3. To further examine the role of Pbx3 in AML maintenance
and progression, we used the CRISPR/Cas9 system to delete Pbx3 in leukemic cells
in the MLL-AF9 induced AML mouse model. We found that Pbx3 deletion significantly
prolonged the survival of leukemic mice and decreased the leukemia burden by
decreasing the capacity of LSCs and promoting LSC apoptosis. In conclusion, we
found that PBX3 is epigenetically aberrant in the LSCs of MLL-r AML and is
essential for leukemia development. Significantly, the differential expression of
PBX3 in normal and malignant hematopoietic cells suggests PBX3 as a potential
prognostic marker and therapeutic target for MLL-r leukemia.
PMID- 28411382
TI - Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube
Defects in the Fetus: Evidence from Case-Control and Family-Based Triad
Approaches.
AB - BACKGROUND: Neural tube defects (NTDs) are caused by the failure of neural tube
formation which occurs during early embryonic development. NTDs are the most
severe and leading cause of fetal mortality. Serine hydroxymethyl transferase
(SHMT1) provides one-carbon units necessary for embryogenesis and defects in one
carbon production result in specific pathological conditions during pregnancy.
The present study is aimed to evaluate the association of SHMT1 C1420T with NTD
risk in the fetus using fetal, maternal and paternal groups by applying both case
control and family-based triad approaches. METHODS: A total of 924 subjects
including 124 NTD case-parent trios (n = 124 * 3 = 372) and 184 healthy control
parent trios (n = 184 * 3 = 552) from Telangana State, South India were analyzed.
DNA from umbilical cord tissues and parental blood samples were extracted, and
genotyped by polymerase chain reaction-restriction fragment length polymorphism.
Statistical analysis used were SPSS, parent-of-origin effect (POE) analysis.
RESULTS: Case-control study design demonstrated fetuses with homozygous variant
genotype (TT) to be at risk toward spina bifida subtype (p = 0.022). Among
parents, fathers with TT genotype were associated with anencephaly (p = 0.018)
and spina bifida subtypes (p = 0.027) in the offspring. Of interest, maternal
paternal-offspring genotype incompatibility revealed maternal CT genotype in
combination with paternal TT genotype increased risk for NTDs in the fetus (CTxTT
= TT; p = 0.021). Family-based parent-of-origin effect linkage analysis revealed
significant maternal over-transmission of variant allele to NTD fetuses (p <
0.01). CONCLUSION: The present study, using both case-control and family-based
triad approach is the first report to demonstrate parental association of SHMT1
C1420T variant in conferring NTD risk in the fetus. Birth Defects Research, 2017.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28411383
TI - 2017 Electronic Posters (ePosters).
PMID- 28411384
TI - 2017 Late-Breaking Abstracts.
PMID- 28411386
TI - Lars O. Svaasand.
PMID- 28411387
TI - Prophylactic dissection of level V in primary mucosal SCC in the clinically N
positive neck: A systematic review.
AB - OBJECTIVE: To review the evidence for level V dissection in the management of
previously untreated mucosal squamous cell carcinoma (SCC) of the head and neck
presenting with nodal metastasis when level V is clinically uninvolved. DATA
SOURCE: The Preferred Reporting Items for Systematic Review and Meta-Analyses
(PRISMA) were used to conduct a systematic review of the current literature,
including all English language articles published after 1990. A literature search
was performed on November 29, 2015, of Medline, EMBASE, Cumulative Index to
Nursing and Allied Health Literature (CINAHL), and the Cochrane Library. REVIEW
METHODS: The search yielded a total of 270 papers. Strict inclusion and exclusion
criteria were applied, leaving 20 eligible papers. Overall prevalence was
calculated using random effect meta-analysis. RESULTS: The overall prevalence of
level V occult disease in the node (N)-positive neck, irrespective of subsite,
was 2.56% (95% confidence interval 1.29-3.84) (2,368 patients and 2,533 necks).
The prevalence of occult level V metastasis was up to 7.7% for oral cavity and
8.3% for oropharyngeal tumors. Five studies reported regional recurrence rates
over variable time periods. There is exceedingly limited data on outcomes, such
as spinal accessory nerve function, quality of life, and perioperative
complications. CONCLUSION: Mucosal head and neck SCC presenting with nodal
metastasis but with level V clinically uninvolved has a low prevalence of occult
level V disease. Routine dissection of level V does not appear to be warranted;
however, a definitive conclusion is unable to be drawn due to limited data on
morbidity and oncological outcomes. Laryngoscope, 127:2074-2080, 2017.
PMID- 28411388
TI - Adiposity across the adult life course and incidence of primary liver cancer: The
NIH-AARP cohort.
AB - Obesity relatively late in adulthood has been consistently associated with
increased risk of primary liver cancer. However, little is known about the role
of early adult adiposity and evolution of adiposity across adulthood in
hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m2 ) in relation
to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a
large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was
retrospectively reported by 303,620 participants. BMI trajectories were
identified using latent class trajectory modeling. Incidence of HCC and ICC was
determined through 2011. Cox proportional hazards modeling was used to calculate
adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372
HCC cases and 104 ICC cases occurred during follow-up. Being obese (BMI >= 30) at
ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3-71.5 years) was
associated with an 86-119% elevated risk of HCC. BMI trajectories that resulted
in obesity were associated with ~80% higher HCC incidence. BMI at age 18, per 5
kg/m2 , was associated with a 34% higher risk of ICC, but the association
attenuated for BMI at older ages. In conclusion, our findings suggest that
maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk.
Future studies with longitudinally collected weight information are warranted to
further elucidate the role of life-course adiposity in liver cancer development.
PMID- 28411389
TI - The comet assay in Folsomia candida: A suitable approach to assess genotoxicity
in collembolans.
AB - The present study shows the comet assay technique being successfully applied for
the first time to one of the most widely used soil organisms in standardized
ecotoxicological tests, Folsomia candida, providing a step forward in assessing
the genotoxicity induced by xenobiotics. Because collembolans have a high content
of chitin, a new methodology was developed in which the heads of the collembolans
were separated from the rest of the body, allowing the hemolymph to leak out.
This procedure allows the cells to be released, and after lysis the genetic
material is available for the comet assay. Among other key procedures, the use of
30 organisms (20- to 22-d-old adults) per replicate and the correct amount of
cells with genetic material (translated as 10 MUL of suspension) applied on the
agarose gel were determinants for the success of the results obtained. The
methodology was validated by exposing F. candida to a representative metallic
element (cadmium) and a representative of organophosphates, the insecticide
dimethoate, for a shorter time period of 10 d, compared with the 28 d for the
International Organization for Standardization 11267 method. Within this method,
the relatively low percentage of DNA damage (30%) observed in controls and the
significant increase in terms of percentage of DNA damage for almost all the
concentrations of dimethoate and Cd (reaching 52% and 56% of damage in the
highest concentrations, respectively) confirmed the genotoxic effect of both
compounds and validated this technique. The comet assay proved to be a sensitive
technique to detect DNA strand breaks in collembolans' cells. Environ Toxicol
Chem 2017;36:2514-2520. (c) 2017 SETAC.
PMID- 28411390
TI - Statin use and mortality among ovarian cancer patients: A population-based cohort
study.
AB - Statin use has been suggested to improve prognosis in cancer patients, however,
for ovarian cancer, the evidence is sparse. From the Danish Cancer Registry, we
identified patients aged 30-84 years with a histologically verified first
diagnosis of epithelial ovarian cancer between 2000 and 2013. Data on filled
prescriptions, death, and potential confounding factors were obtained from
nationwide registers. Cox proportional hazard regression models were used to
calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the
association between post-diagnostic statin use and all-cause or ovarian cancer
specific mortality. Among 4,419 patients with epithelial ovarian cancer, post
diagnostic statin use was not statistically significantly associated with all
cause (HR: 0.90, 95% CI: 0.78-1.04) or ovarian cancer-specific mortality (HR:
0.90, 95% CI: 0.76-1.08). There was little evidence of a dose-response
relationship and the neutral associations persisted in sensitivity analyses. In
women with endometrioid or clear cell tumour histology, cancer-specific mortality
was reduced by 30-40% among statin users compared to non-users, however the
analyses were limited by small numbers. Significantly reduced mortality with
statin use was observed in subcohorts of new users of statins and of patients not
using low-dose aspirin. In conclusion, we found no strong evidence of an
association between post-diagnostic statin use and reduced mortality in ovarian
cancer patients. However, our finding of potential differential susceptibility to
statins among patients with different histologic types of ovarian cancer warrants
further evaluation.
PMID- 28411391
TI - Phenotypic expression of 19q13.32 microdeletions: Report of a new patient and
review of the literature.
AB - The phenotypic manifestations of microdeletions in the 19q13.32 region are still
poorly known. In this paper we report a patient who presented with hypotonia,
developmental delay, facial dysmorphism, micrognathia, kyphoscoliosis, and buried
penis. Chromosomal microarray revealed an interstitial 327 kb de novo
microdeletion in the 19q13.32 region comprising eight genes (ARGHAP35, NPAS1,
TMEM160, ZC3H4, SAE1, BBC3, MIR3190, and MIR3191). Previously reported cases of
microdeletions in the 19q13.32 region were reviewed and compared to our patient,
highlighting the common features of a possible 19q13.32 microdeletion syndrome.
PMID- 28411392
TI - Clinical prognostic markers in stage IIIC melanoma.
AB - BACKGROUND: Although the EORTC 18071-trial has shown a clear survival benefit for
adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant
therapy is important. We aimed to identify prognostic factors for death and
disease recurrence in AJCC stage IIIC melanoma patients. PATIENTS AND METHODS:
Retrospective analysis of patients who underwent lymph node dissection (LND) for
stage IIIC melanoma in our institution between 2000 and 2016. Baseline
characteristics, melanoma-specific survival (MSS), and disease-free survival
(DFS) were assessed, and prognostic factors for recurrence and survival were
analyzed using uni- and multivariable analysis. RESULTS: A total of 205 patients
were included. Median follow-up was 20 months (interquartile range 11-43 months),
median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and
5-year DFS was 23%. N3 (>=4 involved lymph nodes) and extracapsular extension
(ECE) carried an increased risk of disease recurrence after LND and death by
melanoma. Patients with both N3 and ECE had virtually no long-term survival.
CONCLUSIONS: Although survival for patients with stage IIIC is poor in general,
patients with both N3 disease and ECE constitute the group with the worst
prognosis and should be considered for adjuvant therapy with ipilimumab or any
other future effective adjuvant therapy (study).
PMID- 28411393
TI - Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis.
AB - OBJECTIVE: Accumulating evidence supports a role for exosomes in immune
regulation. In this study, we investigated the total circulating exosome
transcriptome in relapsing-remitting multiple sclerosis (RRMS) patients and
healthy controls (HC). METHODS: Next generation sequencing (NGS) was used to
define the global RNA profile of serum exosomes in 19 RRMS patients (9 in
relapse, 10 in remission) and 10 HC. We analyzed 5 million reads and >50,000
transcripts per sample, including a detailed analysis of microRNAs (miRNAs)
differentially expressed in RRMS. The discovery set data were validated by
quantification using digital quantitative polymerase chain reaction with an
independent cohort of 63 RRMS patients (33 in relapse, 30 in remission) and 32
HC. RESULTS: Exosomal RNA NGS revealed that of 15 different classes of
transcripts detected, 4 circulating exosomal sequences within the miRNA category
were differentially expressed in RRMS patients versus HC: hsa-miR-122-5p, hsa-miR
196b-5p, hsa-miR-301a-3p, and hsa-miR-532-5p. Serum exosomal expression of these
miRNAs was significantly decreased during relapse in RRMS. These miRNAs were also
decreased in patients with a gadolinium enhancement on brain magnetic resonance
imaging. In vitro secretion of these miRNAs by peripheral blood mononuclear cells
was also significantly impaired in RRMS. INTERPRETATION: These data show that
circulating exosomes have a distinct RNA profile in RRMS. Because putative
targets for these miRNAs include the signal transducer and activator of
transcription 3 and the cell cycle regulator aryl hydrocarbon receptor, the data
suggest a disturbed cell-to-cell communication in this disease. Thus, exosomal
miRNAs might represent a useful biomarker to distinguish multiple sclerosis
relapse. Ann Neurol 2017;81:703-717.
PMID- 28411394
TI - Improved magnetic resonance fingerprinting reconstruction with low-rank and
subspace modeling.
AB - PURPOSE: This article introduces a constrained imaging method based on low-rank
and subspace modeling to improve the accuracy and speed of MR fingerprinting
(MRF). THEORY AND METHODS: A new model-based imaging method is developed for MRF
to reconstruct high-quality time-series images and accurate tissue parameter maps
(e.g., T1 , T2 , and spin density maps). Specifically, the proposed method
exploits low-rank approximations of MRF time-series images, and further enforces
temporal subspace constraints to capture magnetization dynamics. This allows the
time-series image reconstruction problem to be formulated as a simple linear
least-squares problem, which enables efficient computation. After image
reconstruction, tissue parameter maps are estimated via dictionary-based pattern
matching, as in the conventional approach. RESULTS: The effectiveness of the
proposed method was evaluated with in vivo experiments. Compared with the
conventional MRF reconstruction, the proposed method reconstructs time-series
images with significantly reduced aliasing artifacts and noise contamination.
Although the conventional approach exhibits some robustness to these corruptions,
the improved time-series image reconstruction in turn provides more accurate
tissue parameter maps. The improvement is pronounced especially when the
acquisition time becomes short. CONCLUSIONS: The proposed method significantly
improves the accuracy of MRF, and also reduces data acquisition time. Magn Reson
Med 79:933-942, 2018. (c) 2017 International Society for Magnetic Resonance in
Medicine.
PMID- 28411395
TI - A longitudinal study of smokeless tobacco use and mortality in the United States.
AB - Few studies in the United States have examined longitudinally the mortality risks
associated with use of smokeless tobacco (SLT). The sample of our study was
composed of participants from the National Longitudinal Mortality Study who
completed a single Tobacco Use Supplement to the Current Population Survey
between the years 1985 and 2011. Using survival methods, SLT use at the baseline
survey was examined as a predictor of all-cause mortality and cause-specific
mortalities in models that excluded individuals who had ever smoked cigarettes,
cigars or used pipes (final n = 349,282). The participants had median and maximum
follow-up times of 8.8 and 26.3 years, respectively. Regression analyses
indicated that compared to the never tobacco users, the current SLT users did not
have elevated mortality risks from all cancers combined, the digestive system
cancers and cerebrovascular disease. However, current SLT users had a higher
mortality risk for coronary heart disease (CHD) [hazard ratio (HR) (95% CI) =
1.24 (1.05, 1.46)] relative to never tobacco users. In a separate model, the
elevated risk for CHD mortality corresponded to the use of moist snuff [HR (95%
CI) = 1.30 (1.03, 1.63)]. The associations with CHD mortality could be attributed
to long-term nicotine exposure, other SLT constituents (e.g., metals) or the
confounding effects of CHD risk factors not accounted for in our study. The
study's findings contribute to the ongoing dialogue on tobacco harm reduction and
the US FDA's evaluation of Modified Risk Tobacco Product applications submitted
by American SLT manufacturers.
PMID- 28411396
TI - The usefulness of adding p53 immunocytochemistry to bile drainage cytology for
the diagnosis of malignant biliary strictures.
AB - BACKGROUND: Obstructive jaundice is frequently caused by bile duct strictures.
Determination of malignant strictures is crucial for the initiation of
appropriate treatment. Cytologic examination of bile drainage fluid is an easy
and reproducible method of detecting malignant cells. This method, however,
frequently yields indeterminate results, such as atypia or suspicious of
malignancy, due to difficulties in differentiating malignancy from benign atypia.
Immunocytochemical assessment of p53 expression by cells in bile drainage fluid
may enhance the ability to detect malignancy. METHODS: A total of 139 samples of
bile drainage fluid were obtained from 80 patients. Following cytologic
examination, the samples were incubated with antibody to p53. The performance of
cytology with and without p53 immunocytochemistry was evaluated, with reference
to surgical or clinical findings of benign and malignant biliary strictures.
RESULTS: Bile drainage cytology alone had a sensitivity of 31.6% and a
specificity of 98.4% in the identification of malignant strictures, whereas the
combination of p53 immunocytochemistry and bile drainage cytology had a
sensitivity of 80.3% and a specificity of 92.1%. P53 immunocytochemistry alone
had a sensitivity of 64.5% and a specificity of 92.7% for the identification of
malignant strictures in bile drainage samples with atypical cytology, and a
sensitivity of 85.0% and a specificity of 100.0% in samples with suspicious of
malignancy. CONCLUSION: The addition of p53 immunocytochemistry to bile drainage
cytology can be useful in identifying malignant strictures in samples showing
indeterminate results on bile drainage cytology. Diagn. Cytopathol. 2017;45:592
597. (c) 2017 Wiley Periodicals, Inc.
PMID- 28411397
TI - Chondrosarcoma-like metastasis from a poorly differentiated uterine cervical
squamous cell carcinoma. A unique morphology and diagnostic pitfall in cytology.
AB - Rare cases of metastatic squamous cell carcinoma with chondroid differentiation
from esophageal primary have been reported but none from the uterine cervix.
Given the rarity of this phenomenon and potential diagnostic pitfall, we present
this unusual case. The patient is a 25-year-old woman who presented with
shortness of breath. Computerized tomography (CT) showed several lung and pleural
based nodules. CT-guided core biopsy with touch preparations were performed on
the pleural-based nodule. The touch preparations showed large, spindle-to-oval
shaped cells with pleomorphic nuclei embedded in metachromatic chondroid stroma.
The core biopsies also showed predominantly round-to-spindle shaped cells with
hyperchromatic nuclei and prominent nucleoli embedded in a cartilaginous matrix.
Her past medical history is significant for a poorly differentiated squamous cell
carcinoma of the cervix, which on review showed a typical non-keratinizing
squamous cell carcinoma without sarcomatous differentiation. Immunohistochemical
stains performed on the pleural-based mass showed tumor positivity for AE1/AE3,
CK5/6, p16, and S-100. Similar results were seen when the cervical tumor was
stained retrospectively. Human papilloma virus (HPV) in situ hybridization
performed on both the pleural-based mass and cervical tumor detected the presence
of high-risk HPV subtypes including 16 and 18. These findings supported a lung
metastasis from the prior cervical carcinoma. This case emphasizes that cervical
carcinoma can develop mesenchymal (chondrosarcomatous) differentiation in
metastasis even in tumors presenting with pure epithelial phenotype. Awareness of
this occurrence especially on limited cytology material, knowledge of the prior
history and use of ancillary tests are extremely helpful in arriving at the
correct diagnosis. Diagn. Cytopathol. 2017;45:750-753. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28411398
TI - Bud detachment in hydra requires activation of fibroblast growth factor receptor
and a Rho-ROCK-myosin II signaling pathway to ensure formation of a basal
constriction.
AB - BACKGROUND: Hydra propagates asexually by exporting tissue into a bud, which
detaches 4 days later as a fully differentiated young polyp. Prerequisite for
detachment is activation of fibroblast growth factor receptor (FGFR) signaling.
The mechanism which enables constriction and tissue separation within the
monolayered ecto- and endodermal epithelia is unknown. RESULTS: Histological
sections and staining of F-actin by phalloidin revealed conspicuous cell shape
changes at the bud detachment site indicating a localized generation of
mechanical forces and the potential enhancement of secretory functions in
ectodermal cells. By gene expression analysis and pharmacological inhibition, we
identified a candidate signaling pathway through Rho, ROCK, and myosin II, which
controls bud base constriction and rearrangement of the actin cytoskeleton.
Specific regional myosin phosphorylation suggests a crucial role of ectodermal
cells at the detachment site. Inhibition of FGFR, Rho, ROCK, or myosin II kinase
activity is permissive for budding, but represses myosin phosphorylation,
rearrangement of F-actin and constriction. The young polyp remains permanently
connected to the parent by a broad tissue bridge. CONCLUSIONS: Our data suggest
an essential role of FGFR and a Rho-ROCK-myosin II pathway in the control of cell
shape changes required for bud detachment. Developmental Dynamics 246:502-516,
2017. (c) 2017 The Authors Developmental Dynamics published by Wiley Periodicals,
Inc. on behalf of American Association of Anatomists.
PMID- 28411400
TI - Physiologically Based Pharmacokinetic Modeling Suggests Limited Drug-Drug
Interaction Between Clopidogrel and Dasabuvir.
AB - Dasabuvir, a nonnucleoside NS5B polymerase inhibitor, is a sensitive substrate of
cytochrome P450 (CYP) 2C8 with a potential for drug-drug interaction (DDI) with
clopidogrel. A physiologically based pharmacokinetic (PBPK) model was developed
for dasabuvir to evaluate the DDI potential with clopidogrel, the acyl-beta-D
glucuronide metabolite of which has been reported as a strong mechanism-based
inhibitor of CYP2C8 based on an interaction with repaglinide. In addition, the
PBPK model for clopidogrel and its metabolite were updated with additional in
vitro data. Sensitivity analyses using these PBPK models suggested that CYP2C8
inhibition by clopidogrel acyl-beta-D glucuronide may not be as potent as
previously suggested. The dasabuvir and updated clopidogrel PBPK models predict a
moderate increase of 1.5-1.9-fold for Cmax and 1.9-2.8-fold for AUC of dasabuvir
when coadministered with clopidogrel. While the PBPK results suggest there is a
potential for DDI between dasabuvir and clopidogrel, the magnitude is not
expected to be clinically relevant.
PMID- 28411401
TI - Expression of Stem Cell Markers and Dopamine D2 Receptors in Human and Rat
Prolactinomas.
AB - BACKGROUND Dopamine agonists (DAs) are the first-line treatment for
prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem
like cells (TSLCs) are associated with the tolerance to radiotherapy and
chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to
characterize the expression pattern of stem cell markers and D2R in human and rat
prolactinomas. MATERIAL AND METHODS Human prolactinoma specimens (n=14) were
obtained from patients with surgical resection. The xenograft model of rat
prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were
confirmed by immunohistochemical staining of tumor sections, and the expression
of serum PRL was measured by ELISA. The expression of stem cell markers (CD133,
Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by
immunofluorescence. The proportion of CD133-expressing cells after DA treatment
was evaluated by flow cytometry in vitro. RESULTS We found that a small
subpopulation of cells expressing stem cell markers existed both in human and rat
prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R
expression. Conversely, the D2R-expressing cells showed negative CD133
expression. The proportion of CD133-expressing cells in surviving tumor cells was
significantly increased after DA treatment. CONCLUSIONS Our results confirmed the
existence of cells expressing stem cell markers in human and rat prolactinomas.
Additionally, the CD133-expressing cells might resist DA therapy due to the lack
of D2R expression.
PMID- 28411402
TI - Transcriptomics of cereal-Fusarium graminearum interactions: what we have learned
so far.
AB - The ascomycete fungal pathogen Fusarium graminearum causes the globally important
Fusarium head blight (FHB) disease on cereal hosts, such as wheat and barley. In
addition to reducing grain yield, infection by this pathogen causes major quality
losses. In particular, the contamination of food and feed with the F. graminearum
trichothecene toxin deoxynivalenol (DON) can have many adverse short- and long
term effects on human and animal health. During the last decade, the interaction
between F. graminearum and both cereal and model hosts has been extensively
studied through transcriptomic analyses. In this review, we present an overview
of how such analyses have advanced our understanding of this economically
important plant-microbe interaction. From a host point of view, the
transcriptomes of FHB-resistant and FHB-susceptible cereal genotypes, including
near-isogenic lines (NILs) that differ by the presence or absence of quantitative
trait loci (QTLs), have been studied to understand the mechanisms of disease
resistance afforded by such QTLs. Transcriptomic analyses employed to dissect
host responses to DON have facilitated the identification of the genes involved
in toxin detoxification and disease resistance. From the pathogen point of view,
the transcriptome of F. graminearum during pathogenic vs. saprophytic growth, or
when infecting different cereal hosts or different tissues of the same host, have
been studied. In addition, comparative transcriptomic analyses of F. graminearum
knock-out mutants with altered virulence have provided new insights into
pathogenicity-related processes. The F. graminearum transcriptomic data generated
over the years are now being exploited to build a systems level understanding of
the biology of this pathogen, with an ultimate aim of developing effective and
sustainable disease prevention strategies.
PMID- 28411403
TI - Ni/Ir-Catalyzed Photoredox Decarboxylative Coupling of S-Substituted Thiolactic
Acids with Heteroaryl Bromides: Short Synthesis of Sulfoxaflor and Its SF5
Analog.
AB - Metallaphotoredox cross-coupling reactions have recently emerged as a powerful
tool for the construction of C(sp2 )-C(sp3 ) bonds between alkyl chains and
aromatic systems, including electron-deficient heteroaryls, which are known to be
challenging coupling partners. In this article, we disclose the Ni/Ir-catalyzed
photoredox decarboxylative coupling of readily available S-substituted thiolactic
acids with electron-deficient heteroaryl bromides, which resulted in the
formation of simple but otherwise not easily accessible heteroarenes with
alkylsulfide side chains. To demonstrate a practical use of this coupling
reaction, we have shown its efficiency in the one-step synthesis of a key
intermediate in the synthesis of the recently marketed insecticide Sulfoxaflor,
and for the short synthesis of SF5 -Sulfoxaflor.
PMID- 28411404
TI - Patients' use of and attitudes towards self-medication in rural and remote
Slovenian family medicine practices: a cross-sectional multicentre study.
AB - INTRODUCTION: Self-medication is very common in the general population, but its
prevalence can differ according to the place of residence. The aim of this study
was to determine the prevalence of self-medication in patients attending rural
and remote family physicians, and to detect the important factors that are
associated with it. METHODS: A cross-sectional multicentre study was performed in
24 rural and remote family medicine practices in Slovenia was performed. The aim
was to include 720 patients who visited their family physicians on a particular
day. The authors used a validated questionnaire on self-medication, which
consisted of questions about demographic characteristics (sex, age, education and
working status), questions about health status, questions about self-medication
practices, and questions about attitudes towards self-medication. The level of
participants' trust in different sources of medical information was measured by a
five-point Likert scale. The participants were asked to take into account the
year 2013 when completing the questionnaire. RESULTS: Of 720 invited patients,
371 (51.5%) completed the questionnaire. There were 233 (62.8%) women in the
sample. The mean age of the participants was 48.1 (+/-15.1) years. Self
medication was practised by 300 (80.9%) participants. In multivariate analysis,
the variables independently associated with self-medication were information on
self-medication obtained from pharmacists, and information on self-medication
obtained from relatives. Additionally, some other variables had high odds ratios
such as information on self-medication obtained from books, information on self
medication obtained from media, and reason for self-medication: burdening
physicians. CONCLUSIONS: The practices of self-medication in rural Slovenia as
reported by patients can be defined as moderately safe. People tend to seek more
information on self-medication but the main sources for this are lay informants.
Further studies are needed to explore the safety of such practices.
PMID- 28411406
TI - Discovery of novel 2-substituted-4-(2-fluorophenoxy) pyridine derivatives
possessing pyrazolone and triazole moieties as dual c-Met/VEGFR-2 receptor
tyrosine kinase inhibitors.
AB - In our efforts to develop novel dual c-Met/VEGFR-2 inhibitors as potential
anticancer agents, a series of 2-substituted-4-(2-fluorophenoxy) pyridine
derivatives bearing pyrazolone scaffold were designed and synthesized. The cell
proliferation assay in vitro demonstrated that most target compounds had
inhibition potency on both c-Met and VEGFR-2, especially compound 9h, 12b and
12d. Based on the further enzyme assay in vitro, compound 12d was considered as
the most promising one, the IC50 values of which were 0.11MUM and 0.19MUM for c
Met and VEGFR-2, respectively. Further molecular docking studies suggested a
common mode of interaction at the ATP-binding site of c-Met and VEGFR-2,
indicating that 12d was a potential compound for cancer therapy deserving further
study.
PMID- 28411405
TI - Biomarkers of chronic fluoride exposure in groundwater in a highly exposed
population.
AB - This study examined the relation between fluoride (F-) concentrations in
fingernail clippings and urine and the prevalence and severity of enamel
fluorosis (EF) among Ethiopian Rift Valley populations exposed to high levels of
F- in drinking water. The utility of fingernail clippings as a biomarker for F-
exposure and EF was also assessed for the first time in a high-F- region. The
study recorded the EF status of 386 individuals (10 to 50years old), who consume
naturally contaminated groundwater with widely varying F- concentration (0.6
15mg/L). The mean F- concentrations among residents of communities with primary
reliance on groundwater were 5.1mg/kg (range: 0.5-34mg/kg) in fingernails and
8.9mg/L (range: 0.44-34mg/L) in urine. We show strong positive correlations
between F- in drinking water and 12-hour urinary excretion (r=0.74, p<0.001,
n=287), fingernail F- content (r=0.6, p<0.001, n=258), and mean individual
measures of EF severity as measured using the Thylstrup and Fejerskov (TF) Index
(r=0.42, p<0.001, n=316). The data indicate that both fingernail and urine
measures are good biomarkers for F- exposure and EF outcomes, the latter being
slightly more sensitive. Cases of moderate/severe EF were significantly more
common among younger subjects (10 to 15years old) than older subjects (mostly
>25years old) (p<0.001), consistent with their greater exposure to F- during
early childhood, which is the only period of life the enamel is at risk of
fluorosis. In this younger population, EF may be useful as a biomarker for
identifying individuals with other potential health effects that depend on a
specific age window of susceptibility. The finding of exceptionally high F-
concentrations in water, fingernail clippings and urine in this region should
motivate further investigations of other potential health consequences such as
bone disease and abnormalities in the function of the neurological and endocrine
systems.
PMID- 28411407
TI - New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design,
synthesis and biological evaluation as potential anti-inflammatory and analgesic
agents.
AB - A new series of 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives
10a-h was designed and synthesized for evaluation as selective COX-2 inhibitors,
anti-inflammatory agents and as analgesic agents. All compounds were more
selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity.
Compounds 10a, 10b, 10e and 10f were the most COX-2 selective compounds
(S.I.=10.76, 10.87, 8.69 and 9.14 respectively), the most potent anti
inflammatory derivatives (ED50=65.7, 60.2, 76.3 and 107.4MUmol/kg respectively)
in comparison with Celecoxib (COX-2 S.I.=8.61, ED50=82.2MUmol/kg) and were less
ulcerogenic (ulcer indexes=1.22-3.02) than Ibuprofen (ulcer index=20.25) and
comparable to Celecoxib (ulcer index=2.93). The four derivatives (10a, 10b, 10e
and 10f) showed considerable analgesic activities which are clearly parallel to
their anti-inflammatory activities.
PMID- 28411408
TI - Psychopathology and traffic violations in subjects who have lost their driving
license.
AB - BACKGROUND: The persistence of risky behaviors while driving and traffic
accidents despite campaigns to increase awareness suggest that there may be
underlying causes that maintain proneness to traffic violations. The aim of the
current study was to assess: a) the prevalence of psychopathology in a sample of
people who have lost their driving license due to former traffic violations and
b) the discriminatory capacity of each psychopathological disorder to
differentiate among people with high and low proneness to perform risky behaviors
while driving. METHODS: 383 participants in a course to recover their driving
license after its loss due to previous traffic violations were included. The
International Neuropsychiatric Interview (M.I.N.I.) according to DSM-IV was used
to assess psychopathology. RESULTS: Between 67% and 76.2% of the participants had
been affected by a lifetime psychopathological disorder until the moment of
assessment. The most prevalent diagnoses were substance abuse including alcohol
(52.5-62.7%), ADHD (19.7-28.5%), depression (7.9-14.4%) and anxiety (3.6-12.4%).
Substance abuse and ADHD also showed the strongest set of associations with
specific risk behaviors, but ADHD emerged as the most discriminant disorder to
distinguish between those people at high and low risk of while driving.
CONCLUSIONS: The results of the current study suggest that addressing
psychopathology explicitly to prevent risky behaviors and recidivism while
driving would provide benefits in this area.
PMID- 28411410
TI - Spatio-temporal patterns of event-related potentials related to audiovisual
synchrony judgments in older adults.
AB - Older adults have altered perception of the relative timing between auditory and
visual stimuli, even when stimuli are scaled to equate detectability. To help
understand why, this study investigated the neural correlates of audiovisual
synchrony judgments in older adults using electroencephalography (EEG). Fourteen
younger (18-32 year old) and 16 older (61-74 year old) adults performed an
audiovisual synchrony judgment task on flash-pip stimuli while EEG was recorded.
All participants were assessed to have healthy vision and hearing for their age.
Observers responded to whether audiovisual pairs were perceived as synchronous or
asynchronous via a button press. The results showed that the onset of predictive
sensory information for synchrony judgments was not different between groups.
Channels over auditory areas contributed more to this predictive sensory
information than visual areas. The spatial-temporal profile of the EEG activity
also indicates that older adults used different resources to maintain a similar
level of performance in audiovisual synchrony judgments compared with younger
adults.
PMID- 28411409
TI - Dynamic imaging of AMPA receptor trafficking in vitro and in vivo.
AB - Modulation of synaptic strength through trafficking of AMPA receptors is a
fundamental mechanism underlying synaptic plasticity and has been shown to be an
important process in higher brain functions such as learning and memory. Many
studies have used live time-lapse imaging of fluorescently tagged AMPA receptors
to directly monitor their membrane trafficking in the basal state as well as
during synaptic plasticity. While most of these studies are performed in vitro
using neuronal cell cultures, in the past years technological advances have
enabled the imaging of synaptic proteins in vivo in intact organisms. This has
allowed for visualization of synaptic plasticity on a molecular level in living
and behaving animals. Here, we discuss key studies and approaches using dynamic
imaging to visualize AMPA receptor trafficking in vitro as well as imaging
synaptic proteins, including AMPA receptors, in vivo.
PMID- 28411411
TI - Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old
offspring.
AB - INTRODUCTION: There is evidence, though not consistent, that offspring born to
mothers with subtle decreases in thyroid function early in their pregnancies may
be at risk of cognitive impairments and attention problems. However, other types
of problem behavior have not been addressed thus far. We tested whether maternal
thyroid function in early pregnancy is associated with several types of problem
behavior in offspring at age 5-6 years. METHODS: This was a longitudinal study
that included the data of 2000 mother-child pairs from the Amsterdam Born
Children and their Development study. At a median gestational age of 12.9
(interquartile range: 11.9-14.1) weeks, maternal blood was sampled for assessment
of free T4 and TSH. Overall problem behavior, hyperactivity/inattention, conduct
problems, emotional problems, peer relationship problems and prosocial behavior
were measured at age 5-6 years using the Strengths and Difficulties
Questionnaire, which was filled out by both parents and teachers. RESULTS:
Maternal hypothyroxinaemia <5th percentile was associated with a 1.70 (95%
confidence interval (CI): 1.01-2.86) increased odds of teacher-reported
hyperactivity/inattention after adjustment for confounders. By increasing the cut
off level to <10th percentile, the odds ratio became 1.47 (95% CI: 0.99-2.20).
There were no associations between maternal thyroid function parameters and
hyperactivity/inattention as reported by parents, nor with teacher or parent
reports of other types of problem behavior. CONCLUSIONS: Our results partially
confirm previous observations, showing that early disruptions in the maternal
thyroid hormone supply may be associated with ADHD symptoms in offspring. Our
study adds that there is no evidence for an effect on other types of problem
behavior.
PMID- 28411412
TI - Individual differences in the activity of the hypothalamic pituitary adrenal
axis: Relations to age and cumulative risk in early childhood.
AB - This study examined individual differences in the function of the hypothalamic
pituitary-adrenal (HPA) axis with regard to age and cumulative risk during
challenging laboratory tasks administered at 6, 12, 24, and 36 months. Saliva
samples were collected from a majority-minority sample of N=185 children (57%
African American, 50% female) prior to and following these tasks and later
assayed for cortisol. Cumulative distal risk was indexed via a composite of
maternal marital status, maternal education, income-to-needs ratio, the number of
children in the household, and maternal age at childbirth. Probing of
hierarchical models in which cortisol levels and age were nested within child
revealed significant differences in cortisol as a function of both age and
cumulative risk, such that children exposed to high levels of risk exhibited
higher levels of cortisol both within and across age. These results highlight the
sensitivity of the HPA axis to environmental context at the level of the
individual, even as that sensitivity is manifest against the background of
species-typical biological development.
PMID- 28411414
TI - Laser interstitial thermotherapy (LiTT) in epilepsy surgery.
AB - Besides other innovative stereotactic procedures (radiofrequency
thermocoagulation, focused ultrasound, gamma knife) laser interstitial
thermotherapy (LiTT) provides minimally invasive destruction of pathological soft
tissues which could be especially relevant for epilepsy surgeries involving adult
and pediatric patients. Unlike standard resections, no craniotomy is required;
just a tiny borehole trepanation is sufficient. Damage to cortical areas when
accessing deep lesions can be minimized or completely avoided, and treating
epileptogenic foci near eloquent or even vital brain areas becomes possible.
Here, we briefly describe the history and rationale of laser neurosurgery as well
as the technical key features of the two currently available systems for magnetic
resonance-guided LiTT (Visualase(r), NeuroBlate(r); CE marks pending for both).
We also discuss the published clinical experience with LiTT in the field of
epilepsy surgery (approximately 200 cases) with regard to complications, LiTT
induced, long-term brain structural alterations, seizure outcome, preliminary
neuropsychological findings and first estimates of treatment costs. Overall, the
seizure outcome appears to be slightly worse than for resective surgery. Due to
insufficient research methods (e.g. non-established measures, lack of a control
condition), the expected neuropsychological superiority over resective surgery
has not been unambiguously demonstrated thus far. Also, the cost-benefit ratio
requires further critical evaluation. Clinical, multi-center and adequately
controlled outcome studies of high quality should also accompany the imminent
introduction of LiTT into the field of epilepsy surgery and therewith permit
critical scientific evaluation and rational, individual, clinical decisions.
PMID- 28411413
TI - Sexual intimacy in couples is associated with longer telomere length.
AB - High-quality relationships have been shown to be beneficial for physical and
mental health. This study examined overall relationship satisfaction and
perceived stress as well as daily reports of partner support, partner conflict,
and physical intimacy obtained over the course of one week in a sample of 129
high and low stress mothers. Telomere length was examined in whole blood, as well
as the two cell subpopulations: peripheral blood mononuclear cells (PBMCs) and
granulocytes. Telomerase activity was measured in PBMCs. Analyses revealed no
statistically significant associations of telomere length with current
relationship satisfaction, daily support or conflict, or perceived stress. In
contrast, women who reported any sexual intimacy during the course of the week
had significantly longer telomeres measured in whole blood and PBMCs, but not in
granulocytes. These relationships held covarying for age, body mass index,
perceived stress, the relationship indices, and caregiver status. Sexual intimacy
was not significantly related to PBMC telomerase activity. These data provide
preliminary data that sexual intimacy is associated with longer telomere length.
Future studies investigating these associations are warranted.
PMID- 28411415
TI - Chromosome conformation capture-based studies reveal novel features of plant
nuclear architecture.
AB - Nuclear genome organization has recently received increasing attention due to its
manifold functions in basic nuclear processes, such as replication,
transcription, and the maintenance of genome integrity. Using technologies based
on chromosome conformation capture, such as Hi-C, we now have the possibility to
study the three-dimensional organization of the genome at unprecedented
resolution, shedding light onto a previously unexplored level of nuclear
architecture. In plants, research in this field is still in its infancy but a
number of publications provided first insights into basic principles of nuclear
genome organization and the factors that influence it. Apart from general
aspects, newly discovered three-dimensional conformations, such as the KNOT,
raise special interest on how nuclear organization may influence the function of
the genome in previously unexpected ways.
PMID- 28411416
TI - Plant centromeres.
AB - Plant centromeres, which are determined epigenetically by centromeric histone 3
(CENH3) have revealed surprising structural diversity, ranging from the canonical
monocentric seen in vertebrates, to polycentric, and holocentric. Normally
stable, centromeres can change position over evolutionary times or upon genomic
stress, such as when chromosomes are broken. At the DNA level, centromeres can be
based on single copy DNA or more commonly on repeats. Rapid evolution of
centromeric sequences and of CENH3 protein remains a mystery, as evidence of co
adaptation is lacking. Epigenetic differences between parents can trigger
uniparental centromere failure and genome elimination, contributing to
postzygotic hybridization barriers..
PMID- 28411417
TI - Heart rate variability and cordance in rapid eye movement sleep as biomarkers of
depression and treatment response.
AB - OBJECTIVES: The relevance of rapid eye movement (REM) sleep in affective
disorders originates from its well-known abnormalities in depressed patients, who
display disinhibition of REM sleep reflected by increased frequency of rapid eye
movements (REM density). In this study we examined whether heart rate variability
(HRV) and prefrontal theta cordance, both derived from REM sleep, could represent
biomarkers of antidepressant treatment response. METHODS: In an open-label, case
control design, thirty-three in-patients (21 females) with a depressive episode
were treated with various antidepressants for four weeks. Response to treatment
was defined as a >=50% reduction of HAM-D score at the end of the fourth week.
Sleep EEG was recorded after the first and the fourth week of medication. HRV was
derived from 3-min artifact-free electrocardiogram segments during REM sleep.
Cordance was computed for prefrontal EEG channels in the theta frequency band
during tonic REM sleep. RESULTS: HRV during REM sleep was decreased in depressed
patients at week four as compared to controls (high effect size; Cohen's d > 1),
and showed a negative correlation with REM density in both, healthy subjects and
patients at week four. Further, the fourteen responders had significantly higher
prefrontal theta cordance as compared to the nineteen non-responders after the
first week of antidepressant medication; in contrast, HRV at week one did not
discriminate between responders and non-responders. CONCLUSIONS: Our data suggest
that HRV in REM sleep categorizes healthy subjects and depressed patients,
whereas REM sleep-derived prefrontal cordance may predict the response to
antidepressant treatment in depressed patients.
PMID- 28411418
TI - Quantum mechanics models of the methanol dimer: OH?O hydrogen bonds of beta-d
glucose moieties from crystallographic data.
AB - The interaction of two methanol molecules, simplified models of carbohydrates and
cellulose, was examined using a variety of quantum mechanics (QM) levels of
theory. Energy plots for hydrogen bonding distance (H?O) and angle (OH?O) were
constructed. All but two experimental structures were located in stabilized areas
on the vacuum phase energy plots. Each of the 399 models was analyzed with
Bader's atoms-in-molecules (AIM) theory, which showed a widespread ability by the
dimer models to form OH?O hydrogen bonds that have bond paths and Bond Critical
Points. Continuum solvation calculations suggest that a portion of the energy
stabilized structures could occur in the presence of water. A survey of the
Cambridge Structural Database (CSD) for all donor-acceptor interactions in beta-D
glucose moieties examined the similarities and differences among the hydroxyl
groups and acetal oxygen atoms that participate in hydrogen bonds. Comparable
behavior was observed for the O2H, O3H, O4H, and O6H hydroxyls, acting either as
acceptors or donors. Ring O atoms showed distinct hydrogen bonding behavior that
favored mid-length hydrogen bonds.
PMID- 28411419
TI - Effective adsorption of malachite green using magnetic barium phosphate composite
from aqueous solution.
AB - Magnetic Ba3(PO4)2/Fe3O4-nanoparticle (called BPFN) was prepared, characterized,
and developed as a low-cost adsorbent for malachite green (MG) from aqueous
solution. Factors such as adsorption temperature, pH of solution, dosage of
adsorbent, adsorption kinetics and isotherms were investigated. The maximum
adsorption capacity obtained in this work was 1639mgg-1 at 45 degrees C and pH6.
The adsorption process fitted the pseudo-first-order kinetic model and Langmuir
isotherm model. Evidences from zeta potential, Fourier transform infrared
spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS) data revealed
that the adsorption process was driven by electrostatic attraction, the
interaction between Lewis base N(CH3)2 in MG and Lewis acid Ba sites of BPFN. In
addition, the BPFN could be easily regenerated by a magnet and the adsorption
capacity maintained at 70% after five cycles. The present study suggests that the
BPFN had high potential of removing MG from wastewater.
PMID- 28411420
TI - Corrigendum to "Interaction of vasicine with calf thymus DNA: Molecular docking,
spectroscopic and differential scanning calorimetric insights" [Spectrochim. Acta
A Mol. Biomol. Spectrosc. 180 (2017) 217-223].
PMID- 28411421
TI - Influence of the silver deposition method on the activity of platforms for
chemometric surface-enhanced Raman scattering measurements: Silver films on ZrO2
nanopore arrays.
AB - Deposition of plazmonic metal nanoparticles on nanostructured oxide templates is
an important part in preparation and design of suitable substrates for surface
enhanced Raman scattering (SERS) measurements. In this contribution we analyze
the influence of the Ag deposition methods (magnetron sputtering and evaporation
in vacuum, which are often used interchangeably) on SERS activity of the
resultant Ag-n/ZrO2/Zr composite samples fabricated. We found that deposition of
the same amount of Ag (0.020mg/cm2) on the ZrO2 nanoporous layers using magnetron
sputtering and evaporation in vacuum leads to formation of two different surface
morphologies, which can be distinguished on the basis of high-resolution scanning
electron microscopy (HR-SEM) measurements. Those differences distinctly affect
SERS intensity measured for probe molecules: pyridine and sodium 2
mercaptoethanesulfonate. SERS substrates obtained using evaporation technique are
ca. 1.5 times more efficient than substrates prepared using magnetron sputtering.
PMID- 28411422
TI - Ventilation distribution and lung recruitment with speaking valve use in
tracheostomised patient weaning from mechanical ventilation in intensive care.
AB - PURPOSE: Speaking valves (SV) are used infrequently in tracheostomised ICU
patients due to concerns regarding their putative effect on lung recruitment. A
recent study in cardio-thoracic population demonstrated increased end-expiratory
lung volumes during and post SV use without examining if the increase in end
expiratory lung impedance (EELI) resulted in alveolar recruitment or potential
hyperinflation in discrete loci. MATERIALS AND METHODS: A secondary analysis of
Electrical Impedance Tomography (EIT) data from a previous study was conducted.
EELI distribution and tidal variation (TV) were assessed with a previously
validated tool. A new tool was used to investigate ventilated surface area (VSA)
and regional ventilation delay (RVD) as indicators of alveolar recruitment.
RESULTS: The increase in EELI was found to be uniform with significant increase
across all lung sections (p<0.001). TV showed an initial non-significant decrease
(p=0.94) with subsequent increase significantly above baseline (p<0.001). VSA and
RVD showed non-significant changes during and post SV use. CONCLUSIONS: These
findings indicate that hyperinflation did not occur with SV use, which is
supported by previously published data on respiratory parameters. These data
along with obvious psychological benefits to patients are encouraging towards
safe use of SVs in this critically ill cardio-thoracic patient population. TRIAL
REGISTRATION: Anna-Liisa Sutt, Australian New Zealand Clinical Trials Registry
(ANZCTR). ACTRN: ACTRN12615000589583. 4/6/2015.
PMID- 28411423
TI - Novel urinary biomarkers and the early detection of acute kidney injury after
open cardiac surgeries.
AB - BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac
surgery, recently, several biomarkers have been used to facilitate early
detection of AKI, including Neutrophil-gelatinase-associated-lipocalin (NGAL) and
Kidney-injury-molecule-1 (KIM-1).This study was carried out to study the efficacy
of urinary KIM-1 and NGAL separately and in combination in relation to early
detection and assessment of severity of AKI after cardiac surgeries. METHODS:
This prospective study was carried out on 45 adult patients, of both sexes,
Cleveland score(CCS) (0-5) and scheduled for elective coronary artery bypass
graft (CABG) surgery in Alexandria Main University Hospital, after approval of
the ethical committee and having an informed written consent from every patient.
Patients were screened for renal function tests before surgery and every day for
3 day after surgery. Freshly urine samples were taken from all patients and
centrifuged for microscopic examination of the sediment: preoperative, 2, 12, 24,
and 48 hr after cardiopulmonary bypass (CPB) and for measurement of NGAL and KIM
1; after induction, 2, 6, 12, and 24 hr after CPB. The primary end point was the
incidence of AKI defined by the AKIN criteria of serum creatinine. RESULTS: 11
patients developed AKI. Patients with AKI had a higher AKIN stages and CCS. CPB
time and cross clamp time were significantly higher in the AKI group with a mean
of (90.5+/-16.2) and (60.9+/-8.1) minutes respectively. Serum creatinine started
to be significantly higher in AKI group from the second postoperative day with a
mean value of 1.56+/-0.28 mg/dl compared to a mean value of 0.85+/-0.14 mg/dl in
non-AKI group. Urine sediment score(USS) 1 and 2 were higher in the AKI group
than in the non-AKI group 2 hrs after CPB and till the end of the 2nd day with
area under the curve (AUC) average of (0.865). Urinary NGAL significantly rise in
AKI patients 2 and 6 hr after CPB with corresponding AUC of (0.710 and 0.700) but
uKIM-1 was higher in the AKI group 12 and 24 hr after CPB with AUC (0.725 and
0.703) respectively. Combination of urinary NGAL, KIM-1, and USS yielded AUC of
0.906. CONCLUSIONS: urinary NGAL is early sensitive but KIM-1which appears later
than but is a more specific biomarker to ischemic renal injury. Urinary
microscopic examination was found to be with very high sensitivity and
specificity and injury site informative. The combination of more than one
biomarker increases the accuracy of early detection of AKI after cardiac surgery.
PMID- 28411424
TI - Drug use among transgender people in Ontario, Canada: Disparities and
associations with social exclusion.
AB - INTRODUCTION: We identified the prevalence and correlates of past-year illicit
drug use among transgender people in Ontario, Canada, and disparities with the
age-standardized non-transgender population. METHODS: Data on transgender persons
aged 16+ (n=406) were obtained from Trans PULSE, a respondent-driven sampling
(RDS) survey (2009-2010). Overall and sex-specific estimates of past-year drug
use (cocaine and amphetamines, based on data availability) in the reference
population were obtained from Ontario residents aged 16+ (n=39, 980) in the
Canadian Community Health Survey (2009-2010), and standardized to the overall and
gender-specific transgender age distributions. For regression analyses with Trans
PULSE data, past-year drug use included drug types associated with high risk of
physical, psychological, and social harm to the user, and RDS-II weights were
applied to frequencies and prevalence ratios (PR) derived from blockwise logistic
regression models. RESULTS: An estimated 12.3% (95% CI: 7.7, 17.0) of transgender
Ontarians had used at least one of the specified drugs in the past year, with no
significant difference by gender identity. Transgender Ontarians were more likely
to use both cocaine (standardized prevalence difference; SPD=6.8%; 95% CI=1.6,
10.9) and amphetamines (SPD=SPD=1.3%, 95% CI=0.2, 3.1) as compared to the age
standardized non-transgender population. History of transphobic assault,
homelessness or underhousing, and sex work were associated with greater drug use
among transgender persons. CONCLUSIONS: The prevalence of cocaine and amphetamine
use among transgender people in Ontario, Canada was higher than in the age
standardized reference population. Social exclusion predicted within-group
variation in drug use among transgender persons.
PMID- 28411425
TI - Thoron Mitigation System based on charcoal bed for applications in thorium fuel
cycle facilities (part 1): Development of theoretical models for design
considerations.
AB - Regulating the environmental discharge of 220Rn (historically known as thoron)
and its decay products from thorium processing facilities is important for
protection of environment and general public living in the vicinities. Activated
charcoal provides an effective solution to this problem because of its high
adsorption capacity to gaseous element like radon. In order to design and develop
a charcoal based Thoron Mitigation System, a mathematical model has been
developed in the present work for studying the 220Rn transport and adsorption in
a flow through charcoal bed and estimating the 220Rn mitigation factor (MF) as a
function of system and operating parameters. The model accounts for inter- and
intra-grain diffusion, advection, radioactive decay and adsorption processes.
Also, the effects of large void fluctuation and wall channeling on the mitigation
factor have been included through a statistical model. Closed form solution has
been provided for the MF in terms of adsorption coefficient, system dimensions,
grain size, flow rate and void fluctuation exponent. It is shown that the delay
effects due to intra grain diffusion plays a significant role thereby rendering
external equilibrium assumptions unsuitable. Also, the application of the
statistical model clearly demonstrates the transition from the exponential MF to
a power-law form and shows how the occurrence of channels with low probability
can lower mitigation factor by several orders of magnitude. As a part of aiding
design, the model is further extended to optimise the bed dimensions in respect
of pressure drop and MF. The application of the results for the design and
development of a practically useful charcoal bed is discussed.
PMID- 28411426
TI - Thoron Mitigation System based on charcoal bed for applications in thorium fuel
cycle facilities (part 2): Development, characterization, and performance
evaluation.
AB - Exposure due to thoron (220Rn) gas and its decay products in a thorium fuel cycle
facility handling thorium or 232U/233U mixture compounds is an important issue of
radiological concern requiring control and mitigation. Adsorption in a flow
through charcoal bed offers an excellent method of alleviating the release of
220Rn into occupational and public domain. In this paper, we present the design,
development, and characterization of a Thoron Mitigation System (TMS) for
industrial application. Systematic experiments were conducted in the TMS for
examining the 220Rn mitigation characteristics with respect to a host of
parameters such as flow rate, pressure drop, charcoal grain size, charcoal mass
and bed depth, water content, and heat of the carrier gas. An analysis of the
experimental data shows that 220Rn attenuation in a flow through charcoal bed is
not exponential with respect to the residence time, L/Ua (L: bed depth; Ua:
superficial velocity), but follows a power law behaviour, which can be attributed
to the occurrence of large voids due to wall channeling in a flow through bed.
The study demonstrates the regeneration of charcoal adsorption capacity degraded
due to moisture adsorption, by hot air blowing technique. It is found that the
mitigation factor (MF), which is the ratio of the inlet 220Rn concentration (Cin)
to the outlet 220Rn concentration (Cout), of more than 104 for the TMS is easily
achievable during continuous operation (>1000 h) at a flow rate of 40 L min-1
with negligible (<1 cm of water column) pressure drop. The Thoron Mitigation
System based on adsorption on charcoal bed offers a compact and effective device
to remove 220Rn from affluent air streams in a space constrained domain. The
prototype system has been installed in a thorium fuel cycle facility where it is
being evaluated for its long-term performance and overall effectiveness in
mitigating 220Rn levels in the workplace.
PMID- 28411427
TI - Macroscopic urea-functionalized cadmium sulfide material with high visible-light
photocatalytic activity for rewritable paper application.
AB - A macroscopic urea-functionalized CdS (CdS-U) is synthesized for the first time.
The CdS-U material is formed through the interaction between NH2/NH groups on
urea and COO- groups on sodium oleate-capped CdS nanoparticles (CdS-So NPs). The
CdS-U material exhibites excellent visible light photocatalytic activity and
plasticity and has the potential to be produced as rewritable papers. It is
convenience to produce a large-scale film by CdS-U. Letters can be written on the
CdS-U film and disappear through a dissolution-irradiation process, and then the
CdS-U film can be recycled by drying. This novel CdS-U material might be of
interest and provide a new chance to advance the application of visible light
photocatalyst on rewritable papers.
PMID- 28411428
TI - Highly ordered mesoporous organosilica-titania with ionic liquid framework as
very efficient nanocatalyst for green oxidation of alcohols.
AB - Preparation, characterization and catalytic application of a novel ordered
mesoporous organosilica-titania with ionic liquid framework (ILNOS-Ti) is
developed. The ILNOS-Ti was prepared by surfactant directed simultaneous
hydrolysis and condensation of alkyl-imidazolium ionic liquid and
tetramethoxysilane followed by treatment with tetra-tert-butylorthotitanate
(TBOT) under moderate conditions. The chemical and physical properties of the
material were investigated using TG, EDX, DRIFT, TEM, SEM, small angle XRD and
nitrogen adsorption-desorption analyses. The ILNOS-Ti was applied as efficient
nanocatalyst for the green oxidation of alcohols in the presence of hydrogen
peroxide under mild conditions. The corresponding carbonyl products were obtained
in high yield. The stability, recoverability and reusability of the designed
nanocatalyst were also studied under applied reaction conditions.
PMID- 28411429
TI - Degradation of refractory organic compounds by photocatalytic fuel cell with
solar responsive WO3/FTO photoanode and air-breathing cathode.
AB - A novel solar responsive photocatalytic fuel cell (PFC) consisted of a WO3/FTO
photoanode and an air-breathing cathode was successfully prepared for
simultaneous pollutant degradation and power production. The as-prepared PFC
system exhibited outstanding photocurrent performances, which were attributed to
the combined effects of the large specific surface area and the improved oxygen
transportation by air-breathing cathode design, as well as the enhanced light
absorption by transparent FTO substrate. Oxytetracycline hydrochloride was used
as the model compound in this paper, and parametric effects on the PFC
performances were deeply investigated. Results showed that increasing electrolyte
concentration and light density were effective approaches to enhance power
outputs. In terms of oxytetracycline hydrochloride concentration, the maximum
power density firstly enhanced when oxytetracycline hydrochloride concentration
increased to 0.5mmol/L, then dropped dramatically with further increasing of
oxytetracycline hydrochloride concentration to 2.0mmol/L. The highest short
circuit current density of 372.4MUA/cm2 and maximum power density of 36.3MUW/cm2
were obtained when the PFC operated at the optimum operation condition of
0.1mol/l Na2SO4 electrolyte, 200mW/cm2 light density and 0.5mmol/L
oxytetracycline hydrochloride. The PFC-assisted photocatalytic degradation
experiments also suggested a promising application of the as-prepared PFC system
in refractory wastewater treatment.
PMID- 28411430
TI - The role of surface active species in the fabrication and functionality of edible
solid lipid particles.
AB - Lipid particles are very promising candidates for utilisation as Pickering
stabilisers, and fabrication of these species has been attracting considerable
academic and industrial research. Nonetheless, current understanding of these
systems is hindered by the fact that, as a whole, studies reporting on the
fabrication and Pickering utilisation of lipid particles vary significantly in
processing conditions being utilised and formulation parameters considered. The
present study investigates, under well-controlled processing and formulation
conditions, the fabrication of edible lipid particles from two lipid sources in
the presence of two different types of amphiphilic species (surfactant or
protein) via melt-emulsification and subsequent crystallisation. Fabricated solid
lipid particles were assessed in terms of their particle size, interfacial and
thermal behaviour, as well as stability, as these microstructure attributes have
established links to Pickering functionality. Lipid particle size and stability
were controlled by the type and concentration of the used amphiphilic species
(affecting the melt emulsification step) and the type of lipid source
(influencing the crystallisation step). Interfacial behaviour was closely linked
to the type and concentration of the surface active component used. Finally, the
types of lipid and amphiphilic agents employed were found to affect lipid
particle thermal behaviour the most.
PMID- 28411431
TI - Simultaneous removal of Cd(II), Ni(II), Pb(II) and Cu(II) ions via their
complexation with HBANSA based on a combined ultrasound-assisted and cloud point
adsorption method using CSG-BiPO4/FePO4 as novel adsorbent: FAAS detection and
optimization process.
AB - Ultrasound irradiation, cloud point and adsorption methods were coupled to
develop a new technique for the simultaneous removal of Cd(II), Ni(II), Pb(II)
and Cu(II) ions after their complexation with (E)-4-((2-hydroxybenzylidene)
amino) naphthalene-1-sulfonic acid (HBANSA). In order to reduce cost and improve
practicability of process, chitosan gel (CSG) composited with bismuth(III)
phosphate/iron(III) phosphate nanoparticles (CSG-BiPO4/FePO4) were hydrothermally
synthesized followed by their characterization using FE-SEM, EDS and XRD
analysis. The operational parameters such as metal ions concentration, CSG
BiPO4/FePO4 mass, sonication time and temperature were investigated and optimized
using central composite design (CCD). In addition, the possible significant
correlation between these variables and removal efficiency was studied from which
the maximum efficiencies were obtained at 5.57mg/L, 51.49 degrees C, 0.018g and
10.73min corresponding to metal ions concentration, temperature, CSG-BiPO4/FePO4
and sonication time, respectively. Moreover, at these conditions, the removal
percentages of the Cd(II), Ni(II), Pb(II) and Cu(II) ions were found to be 96.24,
93.73, 95.55 and 97.47, respectively. After applying various isotherms, the
Langmuir isotherm model was found to be most appropriate model for describing and
fitting the experimental equilibrium data and thus maximum mono-layer adsorption
capacities of 8.61, 8.54, 8.65 and 8.62mgg-1 were obtained for Cd(II), Pb(II),
Cu(II) and Ni(II) ions, respectively. The study of kinetics showed well
applicability of pseudo second order kinetic model with maximum mass transfer
rate in adsorption process.
PMID- 28411432
TI - Automated in-line mixing system for large scale production of chitosan-based
polyplexes.
AB - Chitosan (CS)-based polyplexes are efficient non-viral gene delivery systems that
are most commonly prepared by manual mixing. However, manual mixing is not only
poorly controlled but also restricted to relatively small preparation volumes,
limiting clinical applications. In order to overcome these drawbacks and to
produce clinical quantities of CS-based polyplexes, a fully automated in-line
mixing platform was developed for production of large batches of small-size and
homogeneous CS-based polyplexes. Operational conditions to produce small-sized
homogeneous polyplexes were identified. Increasing mixing concentrations of CS
and nucleic acid was directly associated with an increase in size and
polydispersity of both CS/pDNA and CS/siRNA polyplexes. We also found that
although the speed of mixing has a negligible impact on the properties of CS/pDNA
polyplexes, the size and polydispersity of CS/siRNA polyplexes are strongly
influenced by the mixing speed: the higher the speed, the smaller the size and
polydispersity. While in-line and manual CS/pDNA polyplexes had similar size and
PDI, CS/siRNA polyplexes were smaller and more homogenous when prepared in-line
in the non-laminar flow regime compared to manual method. Finally, we found that
in-line mixed CS/siRNA polyplexes have equivalent or higher silencing efficiency
of ApoB in HepG2 cells, compared to manually prepared polyplexes.
PMID- 28411433
TI - Preparation method of Ni@Pt/C nanocatalyst affects the performance of direct
borohydride-hydrogen peroxide fuel cell: Improved power density and increased
catalytic oxidation of borohydride.
AB - The Ni@Pt/C electrocatalysts were synthesized using two different methods: with
sodium dodecyl sulfate (SDS) and without SDS. The metal loading in synthesized
nanocatalysts was 20wt% and the molar ratio of Ni: Pt was 1:1. The structural
characterizations of Ni@Pt/C electrocatalysts were investigated by field emission
scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy
(EDX), X-ray diffraction (XRD), transmission electron microscopy (TEM) and high
resolution transmission electron microscopy (HR-TEM). The electrocatalytic
activity of Ni@Pt/C electrocatalysts toward BH4- oxidation in alkaline medium was
studied by means of cyclic voltammetry (CV), chronopotentiometry (CP),
chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). The
results showed that Ni@Pt/C electrocatalyst synthesized without SDS has superior
catalytic activity toward borohydride oxidation (22016.92AgPt-1) in comparison
with a catalyst prepared in the presence of SDS (17766.15AgPt-1) in NaBH4 0.1M at
25 degrees C. The Membrane Electrode Assembly (MEA) used in fuel cell set-up was
fabricated with catalyst-coated membrane (CCM) technique. The effect of Ni@Pt/C
catalysts prepared with two methods as anode catalyst on the performance of
direct borohydride-hydrogen peroxide fuel cell was studied. The maximum power
density was obtained using Ni@Pt/C catalyst synthesized without SDS at 60 degrees
C, 1M NaBH4 and 2M H2O2 (133.38mWcm-2).
PMID- 28411434
TI - Synthesis and characterization of NiFe2O4@Cu nanoparticles as a magnetically
recoverable catalyst for reduction of nitroarenes to arylamines with NaBH4.
AB - In this research, a simple and efficient method for synthesis of magnetically
separable NiFe2O4@Cu nanocomposite under co-precipitation conditions was
described. X-ray diffraction (XRD), scanning electron microscopy (SEM), energy
dispersive X-ray spectroscopy (EDX), atomic absorption spectroscopy (AAS),
Brunauer-Emmett-Teller (BET) and vibrating sample magnetometer (VSM) analyses
confirmed the construction of NiFe2O4@Cu nanoparticles. The prepared core-shell
nanocomposite showed a satisfactory catalytic activity for NaBH4 reduction of
nitroarenes to arylamines. All reactions were carried out in a mixture of H2O
EtOH (1.5:0.5mL) within 1-12min under reflux conditions. The Cu nanocatalyst can
be easily separated by a magnet and reused seven consecutive runs with no obvious
loss of activity.
PMID- 28411435
TI - The effect of surfactant crystallization on partial coalescence in O/W emulsions.
AB - Partial coalescence is a ubiquitous instability in emulsions whose dispersed
phase is partially crystallized. When emulsions are stabilized with proteins,
interfacial stiffness and long-range repulsive surface forces hinder this type of
instability. The addition of low molecular weight surfactants modifies the
interfacial properties and surface forces, generally promoting partial
coalescence. In the present work, various surfactants (Tween(r) 80, palmitic acid
and monoglycerides) differing in their crystallization temperature were probed
for their ability to induce partial coalescence in model O/W emulsions stabilized
by sodium caseinate. The initially fluid emulsions were submitted to a tempering
cycle leading to the gelation of the system. The extent of partial coalescence
was evaluated by measuring the bulk storage modulus. DSC was used to determine
the melting range of the oil phase and surfactants, while polarized microscopy,
Raman imaging, and surface rheology measurements were performed to characterize
the oil/water interface. The experimental conditions in terms of droplet size,
surfactant-to-protein molar ratio and tempering history favoring partial
coalescence were first explored in presence of Tween(r) 80. We show that partial
coalescence is rather marginal when crystallizable surfactants are added, and
pronounced with liquid surfactants. The phenomena underlying this result,
especially interfacial crystallization of surfactants, are evidenced and
discussed.
PMID- 28411436
TI - Acoustic source localization in an anisotropic plate without knowing its material
properties - A new approach.
AB - Acoustic source localization (ASL) in a highly anisotropic plate is a challenging
task. The basic assumption in many of the currently available techniques is that
the wave propagates along a straight line from the source to the receiving
sensor. However, waves in anisotropic solids propagate along curved lines and
form non-circular wave fronts. As a result, for a highly anisotropic solid the
acoustic source localization techniques that assume straight line propagation of
waves from the source to the receiver are bound to produce a significant error.
In this paper a new technique is introduced for acoustic source localization in
an anisotropic plate by dealing with non-circular shape of wave fronts. Direction
vectors of the wave fronts are computed from the Time-Difference-Of-Arrivals
(TDOA) at three sensors placed in a cluster, then they are cast into a geometric
vector analysis or an optimization process to accurately obtain the acoustic
source location. Two common wave front shapes in highly anisotropic plates,
rhombus and ellipse, are analyzed. Following this analysis, the acoustic source
could be successfully localized without knowing the material properties of the
plate.
PMID- 28411437
TI - Design and construction of a novel 1H/19F double-tuned coil system using PIN
diode switches at 9.4T.
AB - A double-tuned 1H/19F coil using PIN-diode switches was developed and its
performance evaluated. The is a key difference from the previous developments
being that this design used a PIN-diode switch in series with an additionally
inserted inductor in parallel to one of the capacitors on the loop. The probe was
adjusted to 19F when the reverse bias voltage was applied (PIN-diode OFF), whilst
it was switched to 1H when forward current was flowing (PIN-diode ON). S
parameters and Q-factors of single- and double-tuned coils were examined and
compared with/without a phantom on the bench. Imaging experiments were carried
out on a 9.4T preclinical scanner. All coils were tuned at resonance frequencies
and matched well. It is shown that the Q-ratio and SNR of double-tuned coil at
19F frequency are nearly as good as those of a single-tuned coil. Since the
operating frequency was tuned to 19F when the PIN-diodes were turned off, losses
due to PIN-diodes were substantially lower resulting in the provision of
excellent image quality of X-nuclei.
PMID- 28411438
TI - Quantifying a threat: Evidence of a numeric processing bias.
AB - Humans prioritize the processing of threats over neutral stimuli; thus, not
surprisingly, the presence of threats has been shown to alter performance on both
perceptual and cognitive tasks. Yet whether the quantification process is
disrupted in the presence of threat is unknown. In three experiments, we examined
numerical estimation and discrimination abilities in adults in the context of
threatening (spiders) and non-threatening (e.g., flowers) stimuli. Results of the
numerical estimation task (Experiment 1) showed that participants underestimated
the number of threatening relative to neutral stimuli. Additionally, numerical
discrimination data reveal that participants' abilities to discriminate between
the number of entities in two arrays were worsened when the arrays consisted of
threatening entities versus neutral entities (Experiment 2). However,
discrimination abilities were enhanced when threatening content was presented
immediately before neutral dot arrays (Experiment 3). Together, these studies
suggest that threats impact our processing of visual numerosity via changes in
attention to numerical stimuli, and that the nature of the threat (intrinsic or
extrinsic to the stimulus) is vital in determining the direction of this impact.
Intrinsic threat content in stimuli impedes its own quantification; yet threat
that is extrinsic to the sets to be enumerated enhances numerical processing for
subsequently presented neutral stimuli.
PMID- 28411439
TI - Neuropeptide Y enhances proliferation and prevents apoptosis in rat bone marrow
stromal cells in association with activation of the Wnt/beta-catenin pathway in
vitro.
AB - Neuropeptide Y (NPY) exhibits a critical but poorly understood regulatory
signaling function and has been shown to promote proliferation, vascularization
and migration in several types of cells and tissues. However, little is known
about the specific role of NPY in the proliferation and apoptosis of bone marrow
stromal cells (also known as bone marrow-derived mesenchymal stem cells, BMSCs),
which contain a subpopulation of multipotent skeletal stem cells. Based on BrdU
incorporation tests, Cell Counting Kit-8, flow cytometry, quantitative polymerase
chain reaction and western blotting, we showed that NPY significantly promoted
the proliferation of BMSCs in a concentration-dependent manner, with a maximal
effect observed at a concentration of 10-10M for pro-proliferative and 10-12M for
anti-apoptotic activities. Furthermore, NPY significantly increased the
percentage of cells in S and G2/M phases. In addition, NPY exhibited a protective
effect after 24h of serum starvation as illustrated by a reduction in the
apoptosis rate, degree of nuclear condensation, and expression of apoptosis
markers, including caspase-3, caspase-9 and Bax mRNA expression. NPY also
increased the mRNA and protein expression levels of canonical Wnt signaling
pathway proteins, including beta-catenin and c-myc, during the induced
proliferative and anti-apoptotic processes. However, the proliferative and anti
apoptotic activities of NPY were partially blocked by both PD160170 (1MUM) and
DKK1 (0.2MUg/mL). These compounds also blocked the mRNA and protein expression of
beta-catenin, p-GSK-3beta and c-myc. Therefore, the results of the present study
demonstrated that NPY exerts a proliferative and protective effect on BMSCs in a
dose- and time-dependent manner in vitro, and importantly, these effects may be
mediated via its Y1 receptor and involved in activation of the canonical Wnt
signaling pathway.
PMID- 28411440
TI - TWEAK/Fn14 promotes pro-inflammatory cytokine secretion in hepatic stellate cells
via NF-kappaB/STAT3 pathways.
AB - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor
fibroblast growth factor-inducible 14 (Fn14) have been associated with liver
disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound
healing response after liver injury, but there is little information available on
the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the
role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with
TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme
linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Western blotting
and RT-PCR were performed to evaluate the expression of Fn14 after TWEAK
stimulation. Total and phosphorylated of inhibitor-kappaB (I-kappaB), nuclear
factor kappa B (NF-kappaB), Janus kinase 2 (JAK2), and signal transducers and
activators of transcription 3 (STAT3) were examined by western blotting after
TWEAK stimulation and small interfering RNA (siRNA) transfection. The result
showed that TWEAK upregulated the expression of Fn14 and pro-inflammatory factors
interleukin-8 (IL-8), interleukin-6 (IL-6), regulated upon activation normal T
cell expressed and secreted (RANTES), and monocyte chemotactic protein-1 (MCP-1).
In LX-2 cells, the pro-inflammatory cytokine secretion was closely related to the
activation of the NF-kappaB and STAT3 pathways. Furthermore, our research showed
that STAT3 and NF-kappaB could interact with each other, which resulted in a
significant increase of pro-inflammatory cytokine secretion. The activation of NF
kappaB and STAT3 signalling-dependent pro-inflammatory cytokine expression may be
responsible for such a novel principle and new therapeutic targets in chronic
liver disease.
PMID- 28411441
TI - Longitudinal gait and balance decline in Friedreich's Ataxia: A pilot study.
AB - INTRODUCTION: Friedreich's Ataxia (FA) is a devastating, progressive,
neurodegenerative disease. Objective measures that detect changes in neurological
function in FA patients are needed to facilitate therapeutic clinical trials. The
purpose of this pilot study was to analyze longitudinal changes in gait and
balance in subjects with FA using the GAITRite Walkway System(r) and Biodex
Balance SystemTM, respectively, and to test the ability of these measures to
detect change over time compared to the Friedreich's Ataxia Rating Scale (FARS).
METHODS: This was a 24-month longitudinal study comparing ambulatory FA subjects
with age- and gender-matched, healthy controls. Eight FA subjects and 8 controls
were tested at regular intervals using the GAITRite and Biodex Balance systems
and the FARS. RESULTS: In the FA group, comfortable and fast gait velocity
declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months,
respectively. Postural stability indices increased in FA subjects an average of
41% from baseline to 24 months, representing a decline in balance. Subjects with
FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24
months. There were no changes in gait or balance variables in controls. In the FA
group, multiple gait and balance measures correlated significantly with FARS
neurological exam scores. CONCLUSIONS: The GAITRite and Biodex Balance systems
provided objective and clinically relevant measures of functional decline in
subjects with FA that correlated significantly with performance measures in the
FARS. Gait velocity may be an important objective measure to identify disease
progression in adults with FA.
PMID- 28411442
TI - Ankle muscle co-contractions during quiet standing are associated with decreased
postural steadiness in the elderly.
AB - It has been reported that the elderly use co-contraction of the tibialis anterior
(TA) and plantarflexor muscles for longer duration during quiet standing than the
young. However, the particular role of ankle muscle co-contractions in the
elderly during quiet standing remains unclear. Therefore, the objective of this
study was to investigate the association between ankle muscle co-contractions and
postural steadiness during standing in the elderly. Twenty-seven young (27.2+/
4.5yrs) and twenty-three elderly (66.2+/-5.0yrs) subjects were asked to stand
quietly on a force plate for five trials. The center of pressure (COP) trajectory
and its velocity (COPv) as well as the center of mass (COM) trajectory and its
velocity (COMv) and acceleration (ACC) were calculated using the force plate
outputs. Electromyograms were obtained from the right TA, soleus (SOL), and
medial gastrocnemius (MG) muscles. Periods of TA activity (TAon) and inactivity
(TAoff) were determined using an EMG threshold based on TA resting level. Our
results indicate that, in the elderly, the COPv, COMv, and ACC variability were
significantly larger during TAon periods compared to TAoff periods. However, in
the young, no significant association between respective variability and TA
activity was found. We conclude that ankle muscle co-contractions in the elderly
are not associated with an increase, but a decrease in postural steadiness.
Future studies are needed to clarify the causal relationship between (1) ankle
muscle co-contractions and (2) joint stiffness and multi-segmental actions during
standing as well as their changes with aging.
PMID- 28411443
TI - Assessment of stability during gait in patients with spinal deformity-A
preliminary analysis using the dynamic stability margin.
AB - Daily living activities are dynamic, requiring spinal motion through space.
Current assessment of spinal deformities is based on static measurements from
full-spine standing radiographs. Tools to assess dynamic stability during gait
might be useful to enhance the standard evaluation. The aim of this study was to
evaluate gait dynamic imbalance in patients with spinal deformity using the
dynamic stability margin (DSM). Twelve normal subjects and 17 patients with
spinal deformity were prospectively recruited. A kinematic 3D gait analysis was
performed for the control group (CG) and the spinal deformity group (SDG). The
DSM (distance between the extrapolated center of mass and the base of support)
and time-distance parameters were calculated for the right and left side during
gait. The relationship between DSM and step length was assessed using three
variables: gait stability, symmetry, and consistency. Variables' accuracy was
validated by a discriminant analysis. Patients with spinal deformity exhibited
gait instability according to the DSM (0.25m versus 0.31m) with decreased
velocity (1.1ms-1 versus 1.3ms-1) and decreased step length (0.32m versus 0.38m).
According to the discriminant analysis, gait stability was the more accurate
variable (area under the curve AUC=0.98) followed by gait symmetry and
consistency. However, gait consistency showed 100% of specificity, sensitivity,
and accuracy of precision. The DSM showed that patients with spinal malalignment
exhibit decreased gait stability, symmetry, and consistency besides gait time
distance parameter changes. Additional work is required to determine how to apply
the DSM for preoperative and postoperative spinal deformity management.
PMID- 28411444
TI - Continuous and difficult discrete cognitive tasks promote improved stability in
older adults.
AB - Directing attention away from postural control and onto a cognitive task affords
the emergence of automatic control processes. Perhaps the continuous withdrawal
of attention from the postural task facilitates an automatization of posture as
opposed to only intermittent withdrawal; however this is unknown in the aging
population. Twenty older adults (69.9+/-3.5years) stood with feet together on a
force platform for 60s while performing randomly assigned discrete and continuous
cognitive tasks. Participants were instructed to stand comfortably with their
arms by their sides while verbally responding to the auditory stimuli as fast as
possible during the discrete tasks, or mentally performing the continuous
cognitive tasks. Participants also performed single-task standing. Results
demonstrate significant reductions in sway amplitude and sway variability for the
difficult discrete task as well as the continuous tasks relative to single-task
standing. The continuous cognitive tasks also prompted greater frequency of sway
in the anterior-posterior direction compared to single-standing and discrete
tasks, and greater velocity in both directions compared to single-task standing,
which could suggest ankle stiffening. No differences in the simple discrete
condition were shown compared to single-task standing, perhaps due to the
simplicity of the task. Therefore, we propose that the level of difficulty of the
task, the specific neuropsychological process engaged during the cognitive task,
and the type of task (discrete vs. continuous) influence postural control in
older adults. Dual-tasking is a common activity of daily living; this work
provides insight into the age-related changes in postural stability and attention
demand.
PMID- 28411445
TI - Comparison of the Classifier Oriented Gait Score and the Gait Profile Score based
on imitated gait impairments.
AB - Common summary measures of gait quality such as the Gait Profile Score (GPS) are
based on the principle of measuring a distance from the mean pattern of a healthy
reference group in a gait pattern vector space. The recently introduced
Classifier Oriented Gait Score (COGS) is a pathology specific score that measures
this distance in a unique direction, which is indicated by a linear classifier.
This approach has potentially improved the discriminatory power to detect subtle
changes in gait patterns but does not incorporate a profile of interpretable sub
scores like the GPS. The main aims of this study were to extend the COGS by
decomposing it into interpretable sub-scores as realized in the GPS and to
compare the discriminative power of the GPS and COGS. Two types of gait
impairments were imitated to enable a high level of control of the gait patterns.
Imitated impairments were realized by restricting knee extension and inducing leg
length discrepancy. The results showed increased discriminatory power of the COGS
for differentiating diverse levels of impairment. Comparison of the GPS and COGS
sub-scores and their ability to indicate changes in specific variables supports
the validity of both scores. The COGS is an overall measure of gait quality with
increased power to detect subtle changes in gait patterns and might be well
suited for tracing the effect of a therapeutic treatment over time. The newly
introduced sub-scores improved the interpretability of the COGS, which is helpful
for practical applications.
PMID- 28411446
TI - A study of reaching actions in walking infants.
AB - Acquiring motor skills transforms the perceptual and cognitive world of infants
and expands their exploratory engagement with objects. This study investigated
how reaching is integrated with walking among infant walkers (n=23, 14.5-15.5
months). In a walk-to-reach paradigm, diverse object retrieval strategies were
observed. All infants were willing to use their upper and lower bodies in
concert, and the timing of this coordination reflected features of their
environment. Infants with an older walking age (months since walking onset)
retrieved items more rapidly and exploited their non-reaching hand more
effectively during object retrieval than did same-age infants with a younger
walking age. This suggests that the actions of the upper- and lower-body are
flexibly integrated and that this integration may change across development.
Mechanisms that shape sophisticated upper-body use during upright object
retrieval are discussed. Infants flexibly integrate emerging motor skills in the
service of object retrieval in ways not previously documented.
PMID- 28411447
TI - Making progress in early breast cancer: Taking time or accepting risk?
AB - Outcomes for patients diagnosed with early breast cancer in developed countries
have improved substantially over recent decades. Adjuvant therapies have
contributed to this improvement and their benefits have been confirmed in large
randomised controlled trials (RCTs) and meta-analyses. Lower event rates, whilst
welcome, have created problems for RCTs, that need to be larger and often take
longer to provide a reliable result. In an effort to maintain the rate of
progress and to obviate the complexity, cost and time required to conduct large
RCTs, there has been an increased tendency to rely on observational data to
determine a treatment effect and also to accelerate progress by the use of a
surrogate marker (pathological complete remission after neoadjuvant
chemotherapy). We highlight the pitfalls in these approaches and suggest some
simplifications in the conduct of RCTs.
PMID- 28411449
TI - Prenatal concentrations of Perfluoroalkyl substances and early communication
development in British girls.
AB - Perfluoroalkyl substances (PFAS), found in many household products and classed as
endocrine disrupting chemicals, can be transferred through the placenta and are
associated with multiple developmental deficits in offspring. Using data from the
Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the
association between intrauterine exposure to PFAS and early communication
development in 432 mother-daughter dyads at 15 and 38months of age.
Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA),
perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in
maternal serum collected during pregnancy. Early communication development was
measured with the ALSPAC-adapted MacArthur Communicative Development Inventories
for Infants and Toddlers. The infant questionnaire measured verbal comprehension,
vocabulary comprehension and production, nonverbal communication, and social
development. The toddler questionnaire measured language, intelligibility, and
communicative sub-scores. Multivariable linear regression was used to examine
associations between each PFAS exposure and each communication sub-scale score.
The association between maternal PFAS concentrations and early communication
development at 15 and 38months of age varied by maternal age at delivery. In
daughters of younger mothers (<25years of age), every 1ng/mL of PFOS was
associated with a 3.82 point (95% confidence interval (CI): -6.18, -1.47) lower
vocabulary score at 15months and a 0.80 point (95% CI: -1.74, 0.14) lower
language score at 38months. Prenatal exposure to select PFAS was positively and
negatively associated with communication development among girls, with
inconsistent pattern of association across all measured PFAS and endpoints.
PMID- 28411450
TI - Activatable near infrared dye conjugated hyaluronic acid based nanoparticles as a
targeted theranostic agent for enhanced fluorescence/CT/photoacoustic imaging
guided photothermal therapy.
AB - Targeted theranostic nano-system integrating functions of both diagnosis and
therapy shows great potential for improving diagnosis and therapeutic efficacy.
Herein, multifunctional nanoparticle based on activatable hyaluronic acid (HA)
conjugating two near-infrared (NIR) dyes of Cy5.5 and IR825 was successfully
designed and fabricated, and simultaneously used as a carrier for encapsulating
perfluorooctylbromide (PFOB). In this system, PFOB showed good capability to
absorb the X-rays, Cy5.5 on the outer surface acted as a fluorescent dye
activatable by hyaluronidases (Hyals) in the tumor, and IR825 in the core as a
photothermal agent. The obtained nanoparticles (NPs) of PFOB@IR825-HA-Cy5.5 can
be utilized for triple X-ray computed tomography (CT), fluorescence and
photoacoustic imaging. When PFOB@IR825-HA-Cy5.5 NPs were intravenously injected
into the mice bearing HT-29 tumor, efficient tumor accumulation was clearly
observed, as revealed by the triple modal imaging. An in vivo tumor treatment
experiment was conducted by combination of PFOB@IR825-HA-Cy5.5 and near-infrared
laser irradiation, achieving effective tumor ablation in mice. Therefore,
PFOB@IR825-HA-Cy5.5 NPs is a safe, efficient, imageable photothermal nanoprobe,
showing great potential for cancer theranostics.
PMID- 28411448
TI - mTORC1 signaling and the metabolic control of cell growth.
AB - mTOR [mechanistic target of rapamycin] is a serine/threonine protein kinase that,
as part of mTORC1 (mTOR complex 1), acts as an important molecular connection
between nutrient signals and the metabolic processes indispensable for cell
growth. While there has been pronounced interest in the upstream mechanisms
regulating mTORC1, the full range of downstream molecular targets through which
mTORC1 signaling stimulates cell growth is only recently emerging. It is now
evident that mTORC1 promotes cell growth primarily through the activation of key
anabolic processes. Through a diverse set of downstream targets, mTORC1 promotes
the biosynthesis of macromolecules, including proteins, lipids, and nucleotides
to build the biomass underlying cell, tissue, and organismal growth. Here, we
focus on the metabolic functions of mTORC1 as they relate to the control of cell
growth. As dysregulated mTORC1 underlies a variety of human diseases, including
cancer, diabetes, autoimmune diseases, and neurological disorders, understanding
the metabolic program downstream of mTORC1 provides insights into its role in
these pathological states.
PMID- 28411451
TI - Anisotropic tough double network hydrogel from fish collagen and its spontaneous
in vivo bonding to bone.
AB - Soft supporting tissues in the human body, such as cartilages and ligaments, are
tough materials and firmly fixed to bones. These soft tissues, once injured,
cannot regenerate spontaneously in vivo. Developing tough and biocompatible
hydrogels as artificial soft supporting tissues would substantially improve
outcomes after soft tissue injury. Collagen is the main rigid component in soft
connective tissues which is organized in various hierarchical arrays. We have
successfully developed a novel class of collagen fibril-based tough hydrogels
based on the double network (DN) concept using swim bladder collagen (SBC)
extracted from Bester sturgeon fish. The DN hydrogels, SBC/PDMAAm, are composed
of physically/chemically crosslinked anisotropic SBC fibril as the first network
and neutral, biocompatible poly(N,N'-dimethylacrylamide) (PDMAAm) as the second
network. The anisotropic structure of SBC fibril network, which is well retained
in the DN hydrogels, is formed by free injection method, taking advantage of the
excellent fibrillogenesis capacity of SBC. The denaturation temperature of
collagen is improved in the DN hydrogels. These DN gels possess anisotropic
swelling behavior, exhibit excellent mechanical properties comparable to natural
cartilage. The 4 weeks implantation of the gels in the osteochondral defect of
rabbit knee also shows excellent biomechanical performance in vivo. Furthermore,
the hydroxyapatite (HAp) coated DN gels, HAp/SBC/PDMAAm gels, strongly bond to
bone after 4 weeks. This new class of collagen-based hybrid DN gels, as soft and
elastic ceramics, having good biomechanical performance and strong bonding
ability with bone would expand the choice for designing next-generation
orthopedic implants such as artificial cartilage, bone defect repair material in
the load-bearing region of the body.
PMID- 28411452
TI - Peptide valency plays an important role in the activity of a synthetic fibrin
crosslinking polymer.
AB - Therapeutic polymers have the potential to improve the standard of care for
hemorrhage, or uncontrolled bleeding, as synthetic hemostats. PolySTAT, a fibrin
crosslinking peptide-polymer conjugate, has the capacity to rescue fibrin clot
formation and improve survival in a model of acute traumatic bleeding. PolySTAT
consists of a synthetic polymer backbone to which targeting fibrin-binding
peptides are linked. For translation of PolySTAT, the optimal valency of peptides
must be determined. Grafting of fibrin-binding peptides to the poly(hydroxyethyl
methacrylate)-based backbone was controlled to produce peptide valencies ranging
from 0 to 10 peptides per polymer. PolySTATs with valencies of ~4 or greater
resulted in increased clot firmness, kinetics, and decreased breakdown as
measured by thromboelastometry. A valency of ~4 increased clot firmness 57% and
decreased clot breakdown 69% compared to phosphate-buffered saline. This trend
was characterized by neutron scattering, which probed the structure of clots
formed in the presence of PolySTAT. Finally, PolySTAT with valencies of 4 (100%
survival; p = 0.013) and 8 (80% survival; p = 0.063) improved survival compared
to an albumin control in a femoral artery injury model (20% survival). This work
demonstrates tunability of hemostatic polymers and the ability of in vitro assays
to predict in vivo efficacy.
PMID- 28411453
TI - Inhibition of influenza virus infection by multivalent pentacyclic triterpene
functionalized per-O-methylated cyclodextrin conjugates.
AB - Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin
(HA) trimer can block the interaction of HA with its sialic acid receptor. In
this study, a series of multivalent pentacyclic triterpene-functionalized per-O
methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3
dipolar cycloaddition click reaction. A cell-based assay showed that three
compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza
A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity
with IC50 of 4.7 MUM. The time-of-addition assay indicated that compound 28
inhibited the entry of influenza virus into host cell. Further hemagglutination
inhibition (HI) and surface plasmon resonance (SPR) assays indicated that
compound 28 tightly bound to influenza HA protein with a dissociation constant
(KD) of 4.0 MUM. Our results demonstrated a strategy of using per-O-methylated
beta-CD as a scaffold for designing multivalent compounds to disrupt influenza HA
protein-host receptor protein interaction and thus block influenza virus entry
into host cells.
PMID- 28411454
TI - Synthesis and immunogenicity of PG-tb1 monovalent glycoconjugate.
AB - A PG-tb1 hapten from the West Beijing strains of Mycobacterium tuberculosis cell
wall has been efficiently synthesized and conjugated to CRM197 in a simple way as
linker-equipped carbohydrate by applying squaric acid chemistry for an original
neoglycoprotein, creating a potent T-dependent conjugate vaccine. The
intermediate monoester can be easily purified and the degree of incorporation can
be monitored by MALDI-TOF mass spectrometry. After administered systemically in
mice without any adjuvant, the conjugate induced high antigen-specific IgG levels
in serum. Furthermore, following the third immunization, significant antibody
titers frequently exceeding 0.8 million were observed in the sera of mice
vaccinated with PG-CRM197 conjugate which showed the potential for preparation of
TB vaccine.
PMID- 28411455
TI - Identification of 3-substituted-6-(1-(1H-[1,2,3]triazolo[4,5-b]pyrazin-1
yl)ethyl)quinoline derivatives as highly potent and selective mesenchymal
epithelial transition factor (c-Met) inhibitors via metabolite profiling-based
structural optimization.
AB - c-Met/HGF signaling pathway plays an important role in cancer progression, and it
was considered to be related to poor prognosis and drug resistance. Based on
metabolite profiling of (S)-7-fluoro-6-(1-(6-(1-methyl-1H-pyrazol-4-yl)-1H
imidazo[4,5-b]pyrazin-1-yl)ethyl)quinoline (1), a series of 2-substituted or 3
substituted-6-(1-(1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline
derivatives was rationally designed and evaluated. Most of the 3-substituted
derivatives not only exhibited potent activities in both enzymatic and cellular
assays, but also were stable in liver microsomes among different species (human,
rat and monkey). SAR investigation revealed that introducing of N-methyl-1H
pyrazol-4-yl group at the 3-position of quinoline moiety is beneficial to improve
the inhibitory potency, especially in the cellular assays. The influence of
fluorine atom at 7-position or 5, 7-position of quinoline moiety and substituents
at the 6-position of triazolo[4,5-b]pyrazine core on overall activity is not very
significant. Racemate 14, an extremely potent and exquisitely selective c-Met
inhibitor, demonstrated favorable pharmacokinetic properties in rats, no
significant AO metabolism, and effective tumor growth inhibition in c-Met
overexpressed NSCLC (H1993 cell line) and gastric cancer (SNU-5 cell line)
xenograft models. Docking analysis indicated that besides the typical
interactions of most selective c-Met inhibitors, the intramolecular halogen bond
and additional hydrogen bond interactions with kinase are beneficial to the
binding. These results may provide deep insight into potential structural
modifications for developing potent c-Met inhibitors.
PMID- 28411456
TI - Urinary bladder injury during cesarean delivery: Maternal outcome from a
contemporary large case series.
AB - BACKGROUND: Urinary bladder injury is a rare complication during cesarean
delivery. Little is known on maternal outcome following this injury. OBJECTIVE:
To evaluate short and long-term maternal outcome following bladder injury during
cesarean delivery. STUDY DESIGN: A retrospective case series of all pregnancies
complicated by full-thickness bladder injury during cesarean delivery in a single
university affiliated tertiary medical center (August 2007-June 2016). Data on
demographics, labor and surgery parameters, postpartum sequelae, and cystography
were collected and reviewed by study personnel. Short-term maternal outcome
included catheterization period, cystography results (if performed), any febrile
illness and/or need for second operation prior to maternal discharge. Long term
maternal outcome was obtained by searching our urology departmental and
ambulatory database for follow up for all women. Univariate analysis was used to
compare maternal outcome following first or repeat cesarean delivery. RESULTS: Of
17,326 cesarean deliveries performed during study period, 81 (0.47%) were
complicated by bladder injury. Of them, 8 cases (9.9%) occurred during primary
cesarean delivery (overall risk in primary cesarean 0.07%). Of the other 73 cases
that followed repeated cesarean, adhesions were documented in 55 (75.3%) of them.
Six cases (8.2%) had placenta accreta. Bladder injury occurred at peritoneal
entry in 55 (67.9%) cases, and involved the bladder dome in 49 (60.5%) of them.
Injury was diagnosed during cesarean delivery in all but 3 women, in whom
abdominal pain and bloating prompted evaluation on first to third postoperative
day. All 3 underwent re-laparotomy with bladder closure without further adverse
sequelae. Cystography was performed in 35 patients on median postoperative day 8
(6-11 days). Eleven patients had abnormal findings as follows: 5 urinary leakage,
4 bladder wall irregularity and two urinary reflux. Two of the 11 patients (18%)
required additional interventions: One patient required bilateral nephrostomy and
re-laparotomy for bladder closure followed by additional surgery to repair
consequent vesico-vaginal fistula. The second patient required left nephrostomy
and ureteral re-implantation. Both women had combined ureteral and bladder
injury. For the rest of the cohort, no febrile illness or other short- or long
term adverse events were reported. There were no clinically significant
differences in adverse maternal outcomes between women with repeat cesarean
delivery compared to primary cesarean delivery. CONCLUSION: Bladder injury is a
rare complication of cesarean delivery. In our case series, unless there is
combined ureteral and bladder injury, prognosis was favorable without any long
term sequelae.
PMID- 28411457
TI - Getting it right: Culturally safe approaches to health partnership work in low to
middle income countries.
AB - Many health professionals become engaged in international health and education
work in low to middle income countries, often as part of health partnerships.
This type of work, increasingly popular in an age of global health, can present a
number of challenges. Many of these involve cultural factors which are often
acknowledged in the literature on overseas health work but rarely explored in
depth. This paper aims to illustrate the key cultural considerations to be made
by those currently engaged in or considering overseas health and education work
in a low to middle income country. A comprehensive literature review methodology
was used to examine data through the lens of Cultural Safety Theory and as a
result provide guidance for professionals working with international colleagues.
Recommendations for practice are based on the importance of gaining an
understanding of the host country's history and social context and of
professionals examining their own individual worldviews.
PMID- 28411459
TI - A hybrid 3D SEM reconstruction method optimized for complex geologic material
surfaces.
AB - Reconstruction methods are widely used to extract three-dimensional information
from scanning electron microscope (SEM) images. This paper presents a new hybrid
reconstruction method that combines stereoscopic reconstruction with shape-from
shading calculations to generate highly-detailed elevation maps from SEM image
pairs. The method makes use of an imaged glass sphere to determine the
quantitative relationship between observed intensity and angles between the beam
and surface normal, and the detector and surface normal. Two specific equations
are derived to make use of image intensity information in creating the final
elevation map. The equations are used together, one making use of intensities in
the two images, the other making use of intensities within a single image. The
method is specifically designed for SEM images captured with a single secondary
electron detector, and is optimized to capture maximum detail from complex
natural surfaces. The method is illustrated with a complex structured abrasive
material, and a rough natural sand grain. Results show that the method is capable
of capturing details such as angular surface features, varying surface roughness,
and surface striations.
PMID- 28411460
TI - Theoretical insights into the interaction between RunPt13-n (n=4, 7 and 9)
clusters and [BMIM]+ based ionic liquids: Effect of anion.
AB - Density functional theory has been performed to systematically study the
interactions between RunPt13-n (n=4, 7 and 9) clusters and [BMIM]+ based ionic
liquids. Ionic liquids [BMIM][Br], [BMIM][BF4], [BMIM][PF6], [BMIM][CF3SO3], and
[BMIM][NTf2] have different effects on the stability of Ru7Pt6. Ionic liquids
with median size anions of PF6- and CF3SO3- can better improve the stability of
Ru7Pt6 than those with the small anions of Br- and BF4- and large anion of NTf2-.
Based on negative relaxation energies, the stabilities of Ru4Pt9, Ru7Pt6, and
Ru9Pt4 are all enhanced after interacting with [BMIM][CF3SO3]. The stability
enhanced degree is in agreement with the interaction strength. For Ru7Pt6
n{[BMIM][CF3SO3]} (n=1, 2, 3, 4), the interaction between ionic liquid and
cluster plays the primary role in stabilizing the cluster in Ru7Pt6
[BMIM][CF3SO3]. With the increase of the number of [BMIM][CF3SO3], the role of
the interaction in stabilizing the cluster is getting weaker, while the role of
steric protection is getting more important.
PMID- 28411458
TI - Transformation diffusion reconstruction of three-dimensional histology volumes
from two-dimensional image stacks.
AB - Traditional histology is the gold standard for tissue studies, but it is
intrinsically reliant on two-dimensional (2D) images. Study of volumetric tissue
samples such as whole hearts produces a stack of misaligned and distorted 2D
images that need to be reconstructed to recover a congruent volume with the
original sample's shape. In this paper, we develop a mathematical framework
called Transformation Diffusion (TD) for stack alignment refinement as a solution
to the heat diffusion equation. This general framework does not require contour
segmentation, is independent of the registration method used, and is trivially
parallelizable. After the first stack sweep, we also replace registration
operations by operations in the space of transformations, several orders of
magnitude faster and less memory-consuming. Implementing TD with operations in
the space of transformations produces our Transformation Diffusion Reconstruction
(TDR) algorithm, applicable to general transformations that are closed under
inversion and composition. In particular, we provide formulas for translation and
affine transformations. We also propose an Approximated TDR (ATDR) algorithm that
extends the same principles to tensor-product B-spline transformations. Using TDR
and ATDR, we reconstruct a full mouse heart at pixel size 0.92um*0.92um, cut 10um
thick, spaced 20um (84G). Our algorithms employ only local information from
transformations between neighboring slices, but the TD framework allows
theoretical analysis of the refinement as applying a global Gaussian low-pass
filter to the unknown stack misalignments. We also show that reconstruction
without an external reference produces large shape artifacts in a cardiac
specimen while still optimizing slice-to-slice alignment. To overcome this
problem, we use a pre-cutting blockface imaging process previously developed by
our group that takes advantage of Brewster's angle and a polarizer to capture the
outline of only the topmost layer of wax in the block containing embedded tissue
for histological sectioning.
PMID- 28411461
TI - Structural insights into type I and type II of nsp4 porcine reproductive and
respiratory syndrome virus (nsp4 PRRSV) by molecular dynamics simulations.
AB - Porcine reproductive and respiratory virus (PRRSV) causes major economic concerns
for the swine industry worldwide. We have performed molecular dynamics
simulations (MD) and principle component analysis (PCA) to investigate the role
of the catalytic triad and conformational dynamics of type I and type II of nsp4
PRRSV. The results showed that the RMSF of residues 136-142 near the active site
of all models was highly flexible. Moreover, we identified the effect of single
structural mutations of the catalytic triad. The percentage of residue with a
0.1nm RMSF value and PCA results revealed that the mutations affected domain I
and II suggesting the wild types were more stable than the mutants. At the
catalytic triad, the distances between H39 and S118 were very flexible while the
distances between H39 and D64 were very stable. H39, D64 and S118 showed high
occupancy percentage of the hydrogen bond interaction with many residues that are
conserved in PRRSVAS, PRRSVES, LDVC, LDVP and EAV. Moreover, S118 of wild-type
protein formed H-bonds with T134 and G135 but these interactions were lost in
PRRSVAV (S118A) and PRRSVES (S117A) indicating that the substitution of important
H-bond interaction in PRRSVAS (S118A) and PRRSVES (S117A) affected the
flexibility around the catalytic triad, conformation and proteolytic activity.
Overall, our study may provide the structural basic of the catalytic triad and be
useful for testing the protein activity in future experiments.
PMID- 28411462
TI - Flavone polyphenols dominate in Thymus schimperi Ronniger: LC-ESI-MS/MS
characterization and study of anti-proliferative effects of plant extract on AGS
and HepG2 cancer cells.
AB - Thymus schimperi is a highly localized and a rare plant endemic to Ethiopia. An
optimized and validated high-performance liquid chromatography-electrospray
ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was applied to
characterize 23 polyphenolic compounds found in ethyl acetate extracts of the
plant. From those, flavones dominated and luteolin was the major component
contributing 21.83% of the total composition (or 46.05+/-0.59g/kg of fresh sample
weight). Validation data showed a determination coefficient (R2)>=0.997. Limits
of detection (LOD) and quantification (LOQ) were 0.03-0.97 and 0.11-3.23mg/L,
while recovery values spiked at 5 and 50mg/L were between 70.89-115.39 and 67.65
120.19%, respectively. Except for caffeic acid and epicatechin gallate, the
relative standard deviations (%RSDs) were far below 15%, showing acceptable
precision values. The plant extracts inhibited cell proliferation and induced
cell death in human gastric adenocarcinoma (AGS) and liver hepatocellular
carcinoma (HepG2) cancer cells. This is the first report of polyphenolic
components from T. schimperi being characterized using HPLC-ESI-MS/MS. Being
components of many edible vegetables, fruits, and spices, the identified
polyphenols suggest that T. schimperi could be a potential food with promising
health benefits.
PMID- 28411463
TI - Simultaneous separation of taxon-specific crystallins from Mule duck and
characterization of their enzymatic activities and structures.
AB - Methods to obtain pure proteins in large amounts are indispensible in protein
research. We report here a large-scale/simultaneous isolation of taxon-specific
crystallins (E- and delta-crystallin) from the eye lenses of Mule duck. We also
investigate the compositions, enzymatic activities, and structures of these
purified taxon-specific proteins. A relatively mild method of ion-exchange
chromatography was developed to fractionate E-crystallin and delta-crystallin in
large amount, ca. ~6.60mg/g-lens and ~41.0mg/g-lens, respectively. Both
crystallins were identified by electrophoresis, HPLC, and MALDI-TOF-MS. E
Crystallin, with native composition of Mr 142kDa, consisted of two subunits of
35kDa and 36kDa, while delta-Crystallin, with native molecular mass of 200kDa,
comprised single subunit of Mr ~50kDa. Both E- and delta-crystallin were
tetramers. The former showed lactate dehydrogenase (LDH) activity, while the
latter appeared slightly active in an argininosuccinate lyase (ASL) assay. Raman
spectroscopic results indicated that the secondary structures of E- and delta
crystallin were predominantly alpha-helix as evidenced by the vibrational
stretching of amide III over 1260cm-1 and amide I at 1255cm-1, in greatly
contrast to the anti-parallel beta-sheet of alpha- and beta-crystallin as
demonstrated by amide III at 1238cm-1 and amide I at 1672cm-1. The
microenvironments of aromatic amino acids and the status of thiol groups also
vary in different crystallins. The compositions, enzyme activities, and
structures of the E- and delta-crystalline of Mule duck are different from those
of Muscovy duck (Cairina moschata) or Kaiya duck (Anas Platyrhynchos var.
domestica), which reflect faithfully species specificity.
PMID- 28411464
TI - Development, validation and different approaches for the measurement uncertainty
of a multi-class veterinary drugs residues LC-MS method for feeds.
AB - A sensitive method for the simultaneous residues analysis of 62 veterinary drugs
in feeds by liquid chromatography-tandem mass spectrometry has been developed and
validated in accordance to Commission Decision 657/2002/EC. Additionally, limits
of detection (LOD), limits of quantitation (LOQ), matrix effects and measurement
uncertainty were also assessed. Extraction was performed for all analytes and
respective internal standards in a single step and chromatographic separation was
achieved in only 12min. LOQ were set to 0.63-5.00MUgkg-1 (amphenicols), 0.63
30.00MUgkg-1 (avermectins), 0.63MUgkg-1 (benzimidazoles), 0.25-200.00MUgkg-1
(coccidiostats), 0.63-200.00MUgkg-1 (lincosamides and macrolides), 0.25-5.00MUgkg
1 (nitrofurans), 0.63-20.00MUgkg-1 (fluoroquinolones and quinolones), 15.00MUgkg
1 (quinoxaline), 0.63-7.50MUgkg-1 (sulfonamides), 0.63-20.00MUgkg-1
(tetracyclines), 0.25MUgkg-1 (beta-agonists), and 30.00MUgkg-1 (beta-lactams).
The top-down approach was adequate for the calculation of measurement uncertainty
for all analytes, except the banned substances, which should be rather assessed
by the bottom-up approach. Routine analysis of different types of feeds was then
carried out. An interesting profile of residues of veterinary drugs among samples
was revealed, enlightening the need for stricter control in producing animals.
Among the total of 27 feed samples, 20 analytes could be detected/quantified,
ranging from trace levels to very high concentrations. A high throughput
screening/confirmatory method for the residue analysis of several veterinary
drugs in feeds was proposed as a helpful control tool.
PMID- 28411465
TI - Simultaneous and multi-point measurement of ammonia emanating from human skin
surface for the estimation of whole body dermal emission rate.
AB - Ammonia is one of the members of odor gases and a possible source of odor in
indoor environment. However, little has been known on the actual emission rate of
ammonia from the human skin surface. Then, this study aimed to estimate the whole
body dermal emission rate of ammonia by simultaneous and multi-point measurement
of emission fluxes of ammonia employing a passive flux sampler - ion
chromatography system. Firstly, the emission fluxes of ammonia were non
invasively measured for ten volunteers at 13 sampling positions set in 13
anatomical regions classified by Kurazumi et al. The measured emission fluxes
were then converted to partial emission rates using the surface body areas
estimated by weights and heights of volunteers and partial rates of 13 body
regions. Subsequent summation of the partial emission rates provided the whole
body dermal emission rate of ammonia. The results ranged from 2.9 to 12mgh-1 with
an average of 5.9+/-3.2mgh-1 per person for the ten healthy young volunteers. The
values were much greater than those from human breath, and thus the dermal
emission of ammonia was found more significant odor source than the breath
exhalation in indoor environment.
PMID- 28411466
TI - Capillary isoelectric focusing with whole column imaging detection (iCIEF): A new
approach to the characterization and quantification of salivary alpha-amylase.
AB - Saliva is an easily collected biological fluid with potentially important
diagnostic value. While gel electrophoresis is generally used for salivary
analysis, we employed the capillary isoelectric focusing technique to allow for a
rapid, automated mode of electrophoresis. Capillary isoelectric focusing coupled
with UV whole column imaging detection (iCIEF) was used to develop a robust
protocol to characterize salivary alpha-amylase collected from various glands.
Notably, three sample preparation methods were examined: ultrafiltration, gel
filtration, and starch affinity interaction with salivary amylase. Salivary alpha
amylase separated into two major peaks before sample treatment; while both
filtration methods and starch affinity interaction of salivary amylase enhanced
the resolution of isozymes, desalting with gel-filtration displayed the best
recovery and the highest resolution of isozymes. Good agreement existed between
the observed isoelectric points and the values reported in the literature. In
addition, a high level of precision was apparent, and the relative standard
deviation for replicates was less than 0.5% for pIs (peak positions) and below
10% for peak area. Furthermore, saliva secreted from the parotid gland proved to
have a higher amylase content compared to either secretions from the
submandibular/sublingual complex, or whole saliva, as well as amylase enhancement
under stimulation. The results suggest that the iCIEF technique can be used to
accurately resolve and quantitate amylase isozymes in a rapid and automated
fashion, and that gel-filtration should be applied to saliva samples beforehand
to allow for optimal purification and characterization.
PMID- 28411467
TI - Different transcriptomic responses of two marine copepods, Tigriopus japonicus
and Pseudodiaptomus annandalei, to a low dose of mercury chloride (HgCl2).
AB - Mercury (Hg) pollution is a ubiquitous and serious concern in marine
environments, but the response mechanisms of marine animals to Hg pollution
(i.e., toxicity/tolerance) are poorly understood. To compare the global responses
of two marine copepods (Tigriopus japonicus and Pseudodiaptomus annandalei), we
analyzed whole transcriptomes using RNA-seq technology in response to Hg
treatment (a nominal 10MUg/L HgCl2 in seawater) for 5h. Hg was strikingly
accumulated in both copepods under treatment. The Hg concentration in P.
annandalei was higher under metal exposure by approximately 1.4-fold compared
with treated T. japonicus. Among transcriptomic data, 101 genes in T. japonicus
and 18 genes in P. annandalei were differentially regulated in response to Hg
exposure. The up-regulated genes in T. japonicus were concerned with stress,
growth, and development, while the down-regulated ones were mainly related to
immune response. In P. annandalei, most of the differentially expressed genes
were up-regulated, and all were involved in stress response. Our work indicated
that Hg exhibits endocrine-disrupting potential at the transcriptomic level in
marine copepods. Overall, our study demonstrates the species-specific molecular
responses of these two copepods to Hg pollution.
PMID- 28411468
TI - Nine co-localized cytochrome P450 genes of the CYP2N, CYP2AD, and CYP2P gene
families in the mangrove killifish Kryptolebias marmoratus genome: Identification
and expression in response to B[alpha]P, BPA, OP, and NP.
AB - The CYP2 genes are the largest and most diverse cytochrome P450 (CYP) subfamily
in vertebrates. We have identified nine co-localized CYP2 genes (~55kb) in a new
cluster in the genome of the highly resilient ecotoxicological fish model
Kryptolebias marmoratus. Molecular characterization, temporal and tissue-specific
expression pattern, and response to xenobiotics of these genes were examined. The
CYP2 gene clusters were characterized and designated CYP2N22-23, CYP2AD12, and
CYP2P16-20. Gene synteny analysis confirmed that the cluster in K. marmoratus is
similar to that found in other teleost fishes, including zebrafish. A gene
duplication event with diverged catalytic function was observed in CYP2AD12.
Moreover, a high level of divergence in expression was observed among the co
localized genes. Phylogeny of the cluster suggested an orthologous relationship
with similar genes in zebrafish and Japanese medaka. Gene expression analysis
showed that CYP2P19 and CYP2N20 were consecutively expressed throughout embryonic
development, whereas CYP2P18 was expressed in all adult tissues, suggesting that
members of each CYP2 gene family have different physiological roles even though
they are located in the same cluster. Among endocrine-disrupting chemicals
(EDCs), benzo[alpha]pyrene (B[alpha]P) induced expression of CYP2N23, bisphenol A
(BPA) induced CYP2P18 and CYP2P19, and 4-octylphenol (OP) induced CYP2AD12, but
there was no significant response to 4-nonylphenol (NP), implying differential
catalytic roles of the enzyme. In this paper, we identify and characterize a CYP2
gene cluster in the mangrove killifish K. marmoratus with differing catalytic
roles toward EDCs. Our findings provide insights on the roles of nine co
localized CYP2 genes and their catalytic functions for better understanding of
chemical-biological interactions in fish.
PMID- 28411469
TI - Primary hepatocytes from Arctic char (Salvelinus alpinus) as a relevant Arctic in
vitro model for screening contaminants and environmental extracts.
AB - Contaminants find their way to the Arctic through long-range atmospheric
transport, transport via ocean currents, and through increased anthropogenic
activity. Some of the typical pollutants reaching the Arctic (PAHs, PCBs) are
known to induce cytochrome P450 1a (CYP1A) protein expression and ethoxyresorufin
O-deethylase (EROD) activity through the aryl hydrocarbon receptor (AhR). In
addition, some endocrine disrupting chemicals (EDCs) such as estrogen mimics
(xenoestrogens) have been documented in Arctic areas and they may interfere with
natural sexual development and reproduction. In vitro assays that are capable of
detecting effects of such pollutants, covering multiple endpoints, are generally
based on mammalian or temperate species and there are currently no well
characterized cell-based in vitro assays for effect assessment from Arctic fish
species. The present study aimed to develop a high-throughput and multi-endpoint
in vitro assay from Arctic char (Salvelinus alpinus) to provide a non-animal
(alternative) testing method for an ecologically relevant Arctic species. A
method for isolation and exposure of primary hepatocytes from Arctic char for
studying the toxic effects and mode of action (MoA) of pollutants was applied and
validated. The multi-versatility of the bioassay was assessed by classical
biomarker responses such as cell viability (membrane integrity and metabolic
activity), phase I detoxification (CYP1A protein expression, EROD activity) and
estrogen receptor (ER) mediated vitellogenin (Vtg) protein expression using a
selection of model compounds, environmental pollutants and an environmental
extract containing a complex mixture of pollutants. Primary hepatocytes from
Arctic char were successfully isolated and culture conditions optimized to
identify the most optimal assay conditions for covering multiple endpoints. The
hepatocytes responded with concentration-dependent responses to all of the model
compounds, most of the environmental pollutants and the environmental sample
tested. The bioassay response and sensitivity of the hepatocytes from Arctic char
differed slightly from closely related salmonid species, thus highlighting the
need for developing in vitro assays relevant for Arctic species. The present
multi-endpoint in vitro assay offer a highly versatile tool to screen potential
effects of pollutants and complex samples relevant for Arctic exposure scenarios.
PMID- 28411470
TI - Incorporation of spheroidene and spheroidenone into light-harvesting complexes
from purple sulfur bacteria.
AB - Spheroidene and spheroidenone from the non-sulfur bacterium Rhodobacter (Rba.)
sphaeroides were incorporated into diphenylamine (DPA) LH1-RC and LH2 complexes
from sulfur bacteria Allochromatium (Alc.) minutissimum and Ectothiorhodospira
(Ect.) haloalkaliphila in which carotenoid (Car) biosynthesis was inhibited by
~95%. A series of biochemical characteristics of the modified LH2 complexes was
studied (electrophoretic mobility, absorption and CD spectra, Car composition,
Car-to-BChl energy transfer and thermal stability). It was found that the
electrophoretic mobility of the complexes with incorporated Cars did not change
compared to that of the control and DPA-complexes, indicating the absence of any
significant change in the structure of LH complexes upon DPA-treatment and
subsequent incorporation of Cars. The analysis of fluorescence excitation spectra
of the spheroidene-incorporated LH2 complex (LH2:sph) and the spheroidenone
incorporated LH2 complex (LH2:sph-ne) showed that spheroidene and spheroidenone
exhibited relatively low efficiencies of energy transfer to BChl, when
incorporated into the LH2 DPA-complexes from Alc. minutissimum and Ect.
haloalkaliphila, although, they showed high efficiencies, being in their natural
state in the LH2 complexes from Rba. sphaeroides. A significant increase in
thermostability observed for the LH2:sph and LH2:sph-ne complexes with respect to
the LH2 DPA-complexes indicated that the two incorporated Cars stabilized the
structure of the LH2 complexes.
PMID- 28411471
TI - QSAR, docking studies of 1,3-thiazinan-3-yl isonicotinamide derivatives for
antitubercular activity.
AB - The enzyme - enoyl acyl carrier protein reductase (enoyl ACP reductase) is a
validated target for antitubercular activity. Inhibition of this enzyme
interferes with mycolic acid synthesis which is crucial for Mycobacterium
tuberculosis cell growth. In the present work 2D and 3D quantitative structure
activity relationship (QSAR) studies were carried out on a series of thiazinan
Isoniazid pharmacophore to design newer analogues. For 2D QSAR, the best
statistical model was generated using SA-MLR method (r2=0.958, q2=0.922) while 3D
QSAR model was derived using the SA KNN method (q2=0.8498). These studies could
guide the topological, electrostatic, steric, hydrophobic substitutions around
the nucleus based on which the NCEs were designed. Furthermore, molecular docking
was performed to gauze the binding affinity of the designed analogues for enoyl
ACP reductase enzyme. Amongst all the designed analogues the binding energies of
SKS 01 and SKS 05 were found to be -5.267kcal/mol and -5.237kcal/mol respectively
which was comparable with the binding energy of the standard Isoniazid (
6.254kcal/mol).
PMID- 28411472
TI - Thin and sexy vs. muscular and dominant: Prevalence of gendered body ideals in
popular dolls and action figures.
AB - We examined the extent to which popular dolls and action figures were portrayed
with gendered body proportions, and the extent to which these gendered ideals
were associated with heterosexual "success." We coded internet depictions of 72
popular female dolls and 71 popular male action figures from the websites of
three national stores in the United States. Sixty-two percent of dolls had a
noticeably thin body, while 42.3% of action figures had noticeably muscular
bodies. Further, more thin dolls were portrayed with more sex object features
than less thin dolls, including revealing, tight clothing and high-heeled shoes;
bodies positioned with a curved spine, bent knee, and head cant; and with a
sexually appealing facial expression. More muscular male action figures were more
likely than less muscular ones to be shown with hands in fists and with an angry,
emotional expression, suggesting male dominance.
PMID- 28411473
TI - Adaptive attunement of selective covert attention to evolutionary-relevant
emotional visual scenes.
AB - We investigated selective attention to emotional scenes in peripheral vision, as
a function of adaptive relevance of scene affective content for male and female
observers. Pairs of emotional-neutral images appeared peripherally-with
perceptual stimulus differences controlled-while viewers were fixating on a
different stimulus in central vision. Early selective orienting was assessed by
the probability of directing the first fixation towards either scene, and the
time until first fixation. Emotional scenes selectively captured covert attention
even when they were task-irrelevant, thus revealing involuntary, automatic
processing. Sex of observers and specific emotional scene content (e.g., male-to
female-aggression, families and babies, etc.) interactively modulated covert
attention, depending on adaptive priorities and goals for each sex, both for
pleasant and unpleasant content. The attentional system exhibits domain-specific
and sex-specific biases and attunements, probably rooted in evolutionary
pressures to enhance reproductive and protective success. Emotional cues
selectively capture covert attention based on their bio-social significance.
PMID- 28411474
TI - Prior expectations modulate unconscious evidence accumulation.
AB - Unconscious processes have been shown to affect both perception and behaviour.
However, the flexibility of such processes remains unknown. Here we investigate
whether unconscious decisional processes can adapt to the utility of sensory
information. To this end, we had participants gradually accumulate information
from noisy motion stimuli, until a decision was reached. We titrated conscious
awareness of these stimuli by simultaneously presenting a dynamic dichoptic mask.
Crucially, we manipulated the likelihood that the suppressed portion of each
presentation would contain useful information. Our results show that the
statistics of the environment can be used to modulate unconscious evidence
accumulation, resulting in faster choices. Furthermore, computational modelling
revealed that this modulation is due to a change in the quality of unconscious
evidence accumulation, rather than a conscious change in strategy. Together,
these results indicate that unconscious decisional mechanisms are capable of
optimising performance by flexibly adapting to the statistical environment.
PMID- 28411475
TI - Extensibility effect of poly(3-hexylthiophene) on the glucose sensing performance
of mixed poly(3-hexylthiophene)/octadecylamine/glucose oxidase Langmuir-Blodgett
films.
AB - Poly(3-hexylthiophene) (P3HT) is utilized as a material to enhance the glucose
sensing performance of glucose oxidase (GOx) Langmuir-Blodgett (LB) films. To
enhance the extensibility and homogeneity of the P3HT in the LB films,
octadecylamine (ODA) is introduced. The characteristics of the mixed P3HT/ODA
Langmuir monolayers are investigated first and then, utilized as template layers
to adsorb GOx from the subphase, preparing P3HT/ODA/GOx Langmuir-Blodgett films
for glucose sensing. The results show that P3HT molecules tend to aggregate at
the air/liquid interface and, furthermore, the P3HT monolayer has a weak ability
to adsorb GOx from the subphase. By using mixed P3HT/ODA monolayer, the presence
of ODA not only inhibits the aggregation of P3HT, but also increases the
adsorption ability of the monolayer to GOx. The extensibility of P3HT and the
homogeneity of the P3HT/ODA monolayers are closely related to the concentration
of P3HT/ODA stock solutions. On the glucose sensing experiments, the performance
of the P3HT/ODA/GOx LB film is greatly improved due to the presence of P3HT and,
furthermore, the sensibility increases with increasing extensibility of P3HT
molecules. The best sensitivity achieved for the P3HT/ODA/GOx film is 5.4MUAmM
1cm-2 which is over two times the value obtained by the ODA/GOx film (2.3MUAmM
1cm-2).
PMID- 28411476
TI - Trimethyl chitosan-capped silver nanoparticles with positive surface charge:
Their catalytic activity and antibacterial spectrum including multidrug-resistant
strains of Acinetobacter baumannii.
AB - We report a facile route for the green synthesis of trimethyl chitosan nitrate
capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this
synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were
used as silver precursor, reducing agent, and stabilizer, respectively. The
reaction was carried out in a stirred basic aqueous medium at room temperature
without the use of energy-consuming or expensive equipment. We investigated the
effects of the concentrations of NaOH, glucose, and TMCN on the particle size,
zeta potential, and formation yield. The AgNPs were characterized by UV-vis
spectroscopy, photon correlation spectroscopy, laser Doppler anemometry,
transmission electron microscopy, X-ray diffraction, and X-ray photoelectron
spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the
reduction of 4-nitrophenol using NaBH4 as a reducing agent. We evaluated the
antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia
coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth
microdilution method. The results showed that both gram-positive and gram
negative bacteria were killed by the TMCN-AgNPs at very low concentration
(<6.13MUg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity
against clinically isolated multidrug-resistant A. baumannii strains, and the
minimum inhibitory concentration (MIC) was <=12.25MUg/mL.
PMID- 28411477
TI - Comparative surface energetic study of Matrigel(r) and collagen I interactions
with endothelial cells.
AB - Understanding of the surface energetic aspects of the spontaneously deposited
proteins on biomaterial surfaces and how this influences cell adhesion and
differentiation is an area of regenerative medicine that has not received
adequate attention. Current controversies surround the role of the biomaterial
substratum surface chemistry, the range of influence of said substratum, and the
effects of different surface energy components of the protein interface.
Endothelial cells (ECs) are a highly important cell type for regenerative
medicine applications, such as tissue engineering, and In-vivo they interact with
collagen I based stromal tissue and basement membranes producing different
behavioral outcomes. The surface energetic properties of these tissue types and
how they control EC behavior is not well known. In this work we studied the
surface energetic properties of collagen I and Matrigel(r) on various previously
characterized substratum polyurethanes (PU) via contact angle analysis and
examined the subsequent EC network forming characteristics. A combinatorial
surface energy approach was utilized that compared Zisman's critical surface
tension, Kaelble's numerical method, and van Oss-Good-Chaudhury theory (vOGCT).
We found that the unique, rapid network forming characteristics of ECs on
Matrigel(r) could be attributed to the apolar or monopolar basic interfacial
characteristics according to Zisman/Kaelble or vOGCT, respectively. We also found
a lack of significant substratum influence on EC network forming characteristics
for Matrigel(r) but collagen I showed a distinct influence where more apolar PU
substrata tended to produce higher Lewis acid character collagen I interfaces
which led to a greater interaction with ECs. Collagen I interfaces on more polar
PU substrata lacked Lewis acid character and led to similar EC network
characteristics as Matrigel(r). We hypothesized that bipolar character of the
protein film favored cell-substratum over cell-cell adhesive interactions which
resulted in less rapidly forming but more stable networks.
PMID- 28411478
TI - A supramolecular nanoparticle system based on beta-cyclodextrin-conjugated poly-l
lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent
targeting hepatocellular carcinoma.
AB - A novel supramolecular nanoparticle system with core-shell structure was designed
based on beta-cyclodextrin-conjugated poly-l-lysine (PLCD) and hyaluronic acid
for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma
(HCC). PLCD was synthesized by the conjugation of monoaldehyde activated beta
cyclodextrin with poly-l-lysine via Shiff's base reaction. Doxorubicin, as a
model therapeutic drug, was included into the hydrophobic cavity of beta
cyclodextrin in PLCD through host-guest interaction. OligoRNA, as a model gene,
was further condensed into the inclusion complexes by electrostatic interaction
to form oligoRNA and doxorubicin co-loaded supramolecular nanoparticle system.
Hyaluronic acid, which is often over-expressed by HCC cells, was coated on the
surface of the above nanoparticles to construct HCC-targeted nanoparticle system.
These nanoparticles had regular spherical shape with classic "core-shell"
structure, and their size and zeta potential were 195.8nm and -22.7mV,
respectively. The nanoparticles could effectively deliver doxorubicin and
oligoRNA into HCC cells via CD44 receptor-mediated endocytosis and significantly
inhibit the cell proliferation. In the nude mice bearing MHCC-97H tumor, the
nanoparticles could be efficiently accumulated in the tumor, suggesting their
strong hepatoma-targeting capability. These findings demonstrated that this novel
supramolecular nanoparticle system had a promising potential for combining gene
therapy and chemotherapy to treat HCC.
PMID- 28411479
TI - Aged patients with metastatic castration resistant prostate cancer: Should we
treat with chemotherapy?
AB - Prostate cancer largely affects aged men and as life expectancy continues to
increase, it is likely to be a growing burden requiring an adequate management.
Aging is a heterogeneous process, thus, to assess the individual state of health
when making decisions is essential. Comprehensive geriatric assessment allows a
detailed evaluation of the state of health of a specific subject and can modify
the therapeutic decision. It is still not commonly used because it is time
consuming. Chemotherapy should be administered equally in aged well-fit patients
as in the general population as per the SIOG (International society of geriatric
oncology) recommendations for geriatric evaluation and treatment in prostate
cancer patients. Chemotherapy with docetaxel or cabazitaxel is expected to have
an efficacy and toxicity similar to younger patients and they might be considered
treatment options for these patients among others. In vulnerable or frail
patients, weekly or biweekly docetaxel regimens are acceptable treatment options.
PMID- 28411480
TI - Hemorrhagic fever with renal syndrome in Albania. Focus on predictors of acute
kidney injury in HFRS.
AB - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent borne
zoonosis, caused by the members of the family Bunyaviridae, genus Hantavirus. The
main clinical features of the infection by this virus family are fever,
thrombocytopenia and acute kidney injury. OBJECTIVE: The aim of our study was to
identify, for the first time, characteristic features of HFRS in the Albanian
population. STUDY DESIGN: The study comprised 33 consecutive patients admitted
with suspected HFRS from April 2011-April 2016 at one center. Clinical diagnosis
was confirmed by ELISA and real-time PCR. Statistical analysis was performed to
identify prognostic markers and indicators of disease severity. RESULTS: The
virus strain causing HFRS was Dobrava type in all 33 cases. The disease outbreaks
occurred during the period June-July. Mean hospital stay was 15.7+/-6.9days. 29
(88%) of the patients were male. The mean age was 39.7+/-14.1. 16 (48.5%)
patients were from Northeast Albania. 8 (24.2%) patients required dialysis. The
strongest correlation was the inverse relationship of nadir platelet count with
urea and creatinine, p<0.0001, p<0.0079 respectively. Creatinine and hyponatremia
were inversely correlated p=0.0007, whereas hyponatremia and nadir platelet count
had the highest sensitivity and specificity for development of severe AKI, 92.6%,
100%; 88.9%, 83.3% respectively. Mortality rate was 9.09%. CONCLUSION: HFRS is a
severe viral disease in Albania caused by Dobrava strain. It is associated with
high mortality, 9.09% in our cohort. In our study, thrombocytopenia, urinary
volume, hyponatremia were indicators of more severe disease.
PMID- 28411481
TI - A re-evaluation of the final step of vanillin biosynthesis in the orchid Vanilla
planifolia.
AB - A recent publication describes an enzyme from the vanilla orchid Vanilla
planifolia with the ability to convert ferulic acid directly to vanillin. The
authors propose that this represents the final step in the biosynthesis of
vanillin, which is then converted to its storage form, glucovanillin, by
glycosylation. The existence of such a "vanillin synthase" could enable
biotechnological production of vanillin from ferulic acid using a "natural"
vanilla enzyme. The proposed vanillin synthase exhibits high identity to cysteine
proteases, and is identical at the protein sequence level to a protein identified
in 2003 as being associated with the conversion of 4-coumaric acid to 4
hydroxybenzaldehyde. We here demonstrate that the recombinant cysteine protease
like protein, whether expressed in an in vitro transcription-translation system,
E. coli, yeast, or plants, is unable to convert ferulic acid to vanillin. Rather,
the protein is a component of an enzyme complex that preferentially converts 4
coumaric acid to 4-hydroxybenzaldehyde, as demonstrated by the purification of
this complex and peptide sequencing. Furthermore, RNA sequencing provides
evidence that this protein is expressed in many tissues of V. planifolia
irrespective of whether or not they produce vanillin. On the basis of our
results, V. planifolia does not appear to contain a cysteine protease-like
"vanillin synthase" that can, by itself, directly convert ferulic acid to
vanillin. The pathway to vanillin in V. planifolia is yet to be conclusively
determined.
PMID- 28411482
TI - Guaianolide sesquiterpenoids from Ainsliaea yunnanensis.
AB - Six previously undescribed C17-guaianolides, a previously undescribed guaianolide
alkaloid, and two previously undescribed guaianolides as well as 10 known
guaianolides were obtained from an ethanol extract of Ainsliaea yunnanensis
Franch. The chemical structures of all previously reported sesquiterpenoids were
determined by extensive NMR spectroscopic analysis in combination with a modified
Mosher's method. All isolates were in vitro screened for inhibitory effect
against nitric oxide release in RAW 264.7 macrophages stimulated by LPS.
Zaluzanin C remarkably inhibited the production of nitric oxide with an IC50
value of 6.54 MUM.
PMID- 28411483
TI - Guidelines for consistent characterisation and documentation of plant source
materials for studies in phytochemistry and phytopharmacology.
AB - Plants are still by far the most important source of natural products. For higher
plants as source materials identification and documentation are less challenging
than for many other groups of organisms such as microorganisms or marine
invertebrates. Nonetheless, many studies in natural products chemistry and
phytopharmacology involving higher plants are flawed because the plant material
is erroneously assigned, inaccurately documented, untraceable, or not named in
accordance with the rules of nomenclature. Recently, the importance of the proper
usage of plant nomenclature has been highlighted in a dedicated series of
articles in the Journal of Ethnopharmacology and the importance of taxonomic and
geographic information in a viewpoint in Natural Products Reports. Here, the
importance of three related points is being emphasized: a) the traceability of
the identification of plant source materials, b) easy access to vouchers and
digital vouchers of the studied plants, and c) standards for accurate geographic
data about the collection sites of these plants.
PMID- 28411484
TI - Parental monitoring, adolescent dishonesty and underage drinking: A nationally
representative study.
AB - Little research has connected underage drinking with adolescent information
management strategies. The present study uses longitudinal analyses to
theoretically link adolescent lying with parental "monitoring knowledge," and, in
turn, with prospective adolescent drinking, in a large nationally representative
sample of U.S. seventh- and eighth-graders (N = 4020). Structural equation
modeling evaluated and supported, two key hypotheses: (1) dishonesty promotes
future alcohol use by decreasing parental monitoring knowledge, and (2)
dishonesty directly predicts alcohol consumption independent of its effects on
parental monitoring. Maternal warmth and adolescent satisfaction with maternal
relationships, but not parental control, were associated with lessened lying, and
predicted parental monitoring and underage drinking. Our data implicate the role
of adolescent agency for parental monitoring and highlight advantages of cohesive
as opposed to over-restrictive parenting.
PMID- 28411485
TI - Cerebral and muscle microvascular oxygenation in children with sickle cell
disease: Influence of hematology, hemorheology and vasomotion.
AB - The present study investigated cerebral and muscle hemoglobin oxygen saturation
(tissue oxygen index, TOI) in children with sickle cell anemia (SS), sickle cell
hemoglobin C disease (SC) and healthy children (AA). TOI was measured by near
infrared spectroscopy (NIRS) and spectral analysis of the TOI variability was
used to assess flowmotion and vasomotion. Arterial oxyhemoglobin saturation
(SpO2), hemorheological and hematological parameters were also measured in SS and
SC children. Both TOI were lower in SS compared to both AA and SC children, with
SC exhibiting lower values than AA children. Cerebral vasomotion expressed in
absolute values was enhanced in SS compared to AA and SC children. Muscle
vasomotion did not differ between the three groups. Hematocrit, SpO2 and red
blood cell deformability were positively associated with cerebral TOI in SS
children. We demonstrated that 1) cerebral and muscle TOI were markedly decreased
in SS children while the decrease of TOI was milder in SC children, 2) cerebral
TOI level was associated with several biological markers in SS children only and
3) cerebral vasomotion was enhanced in SS, possibly to counterbalance the effects
of chronic cerebral hypoxia.
PMID- 28411486
TI - The effect of age and knee osteoarthritis on muscle activation patterns and knee
joint biomechanics during dual belt treadmill gait.
AB - PURPOSE: To compare a group of individuals with moderate medial compartment knee
osteoarthritis (OA) to both an age-matched asymptomatic group of older adults and
younger adults to determine whether differences in knee joint muscle activation
patterns and joint biomechanics exist during gait between these three groups.
SCOPE: 20 young adults, 20 older adults, and 40 individuals with moderate knee OA
were recruited. Using standardized procedures, surface electromyograms were
recorded from the vastus lateralis and medialis, rectus femoris and the medial
and lateral hamstrings. All individuals walked on a dual belt instrumented
treadmill while segment motions and ground reaction forces were recorded.
Sagittal plane motion and net external sagittal and frontal plane moments were
calculated. Discrete measures and principal component analyses extracted
amplitude and temporal waveform features. Analysis of Variance models using
Bonferroni corrections determined between and within group differences in these
gait features (alpha=0.05). CONCLUSIONS: Individuals with knee OA have distinct
biomechanics and muscle activation patterns when compared to age-matched
asymptomatic adults and younger adults whereas differences between the young and
older adults were few and included only measures of muscle activation amplitude.
PMID- 28411487
TI - The relationship of corticospinal excitability with pain, motor performance and
disability in subjects with chronic wrist/hand pain.
AB - There is a growing body of evidence of changes in corticospinal excitability
associated with musculoskeletal disorders, however there is a lack of knowledge
of how these changes relate to measures of pain, motor performance and
disability. An exploratory study was performed utilizing Transcranial Magnetic
Stimulation to investigate differences in corticospinal excitability in the
Abductor Pollicis Brevis (APB) between 15 pain-free subjects and 15 subjects with
chronic wrist/hand pain and to determine how corticospinal excitability was
associated with measures of pain (visual analog scale, AUSCANTM), hand motor
performance (isometric and key pinch strength, Purdue Pegboard Test), disability
(AUSCANTM), and spinal motoneuronal excitability. Input-output curves
demonstrated increased corticospinal excitability of the APB in the affected hand
of subjects with chronic pain (p<0.01). Changes in corticospinal excitability
were significantly correlated with pain intensity (r=0.77), disability (r=0.58),
and negatively correlated with motoneuronal excitability (r=-0.57). Corticospinal
excitability in subjects with heterogeneous injuries of the wrist/hand was
associated with disability and pain.
PMID- 28411488
TI - Inter-joint coordination of posture on a seesaw device.
AB - Even though specific adjustments of the multi-joint control of posture have been
observed when posture is challenged, multi-joint coordination on a seesaw device
has never been accurately assessed. The current study was conducted in order to
investigate the multi-joint coordination when subjects were standing on either a
seesaw device or on a stable surface, with the eyes open or closed. Eighteen
healthy active subjects were recruited. A principal component analysis and a Self
Organizing Maps analysis were performed on the joint angles in order to detect
and characterize dominant coordination patterns. Intermuscular EMG coherence was
analysed in order to assess the neurophysiological mechanisms associated with
these coordination patterns. The results illustrated a multi-joint organization
of posture on both stable ground and on the seesaw, with a higher variability
among the individual postural responses observed when standing on the seesaw.
These findings challenge the classical assumption of ankle mechanisms as
dominating control on seesaw devices and confirm that inter-joint coordination in
postural control is strongly modulated by stance conditions. When standing on the
seesaw without vision, a decrease in intermuscular coherence was observed without
any impact on the joint coordination patterns, likely due to an increase
dependence on proprioceptive information.
PMID- 28411490
TI - Sequential batch thermophilic solid-state anaerobic digestion of lignocellulosic
biomass via recirculating digestate as inoculum - Part I: Reactor performance.
AB - Sequential batch thermophilic (55 degrees C) solid-state anaerobic digestion (SS
AD) of yard trimmings was evaluated at a total solids (TS) content of 22% via
recirculating digestate as the inoculum. The substrate-to-inoculum (S/I) ratio of
1 (TS basis) was favored over 2 and 3 due to significantly higher methane yield
and volumetric productivity. At an S/I ratio of 1, sequential batch SS-AD
gradually reached steady state by 3 runs (30days/run) with increases in both
methane yields (up to 11.5%) and cellulose degradation (up to 55%), indicating
that recirculated digestate could be a feasible inoculum to establish long term
stable SS-AD of lignocellulosic biomass. The initial sharp increases of volatile
fatty acids during runs 2-4 indicated faster hydrolysis of organic matter than
during run 1, suggesting that microbes were probably more acclimated due to
digestate recirculation. At steady state, 51% (w/w) of the digestate was
recirculated as the inoculum.
PMID- 28411489
TI - Kale BoRACK1 is involved in the plant response to salt stress and Peronospora
brassicae Gaumann.
AB - The receptor for activated C kinase 1 (RACK1) belongs to a protein subfamily
containing a tryptophan-aspartic acid-domain (WD) repeat structure. Compelling
evidence indicates that RACK1 can interact with many signal molecules and affect
different signal transduction pathways. In this study, a kale (Brassica oleracea
var. acephala f.tricolor) RACK1 gene (BoRACK1) was cloned by RT-PCR. The amino
acid sequence of BoRACK1 had seven WD repeats in which there were typical GH
(glycine-histidine) and WD dipeptides. Comparison with AtRACK1 from Arabidopsis
revealed 87.1% identity at the amino acid level. Expression pattern analysis by
RT-PCR showed that BoRACK1 was expressed in all analyzed tissues of kale and that
its transcription in leaves was down-regulated by salt, abscisic acid, and H2O2
at a high concentration. Overexpression of BoRACK1 in kale led to a reduction in
symptoms caused by Peronospora brassicae Gaumann on kale leaves. The expression
levels of the pathogenesis-related protein genes, PR-1 and PRB-1, increased 2.5-4
fold in transgenic kale, and reactive oxygen species production was more active
than in the wild-type. They also exhibited increased tolerance to salt stress in
seed germination. H2O2 may also be involved in the regulation of BoRACK1 during
seed germination under salt stress. Quantitative real-time PCR analyses showed
that the transcript levels of BoRbohs genes were significantly higher in
overexpression of BoRACK1 transgenic lines. Yeast two-hybrid assays showed that
BoRACK1 could interact with WNK8, eIF6, RAR1, and SGT1. This study and previous
work lead us to believe that BoRACK1 may form a complex with regulators of plant
salt and disease resistance to coordinate kale reactions to pathogens.
PMID- 28411491
TI - Production of bio-sugar and bioethanol from coffee residue (CR) by acid-chlorite
pretreatment.
AB - Nowadays, coffee residue (CR) after roasting is recognized as one of the most
useful resources in the world for producing the biofuel and bio-materials. In
this study, we evaluated the potential of bio-sugar and bioethanol production
from acid-chlorite treated CR. Notably, CR treated three times with acid-chlorite
after organic solvent extraction (OSE-3), showed the high monosaccharide content,
and the efficient sugar conversion yield compared to the other pretreatment
conditions. The OSE-3 (6% substrate loading, w/v) can produce bio-sugar (0.568g/g
OSE-3). Also, simultaneous saccharification and fermentation (SSF) produced
ethanol (0.266g/g OSE-3), and showed an ethanol conversion yield of 73.8% after a
72-h reaction period. These results suggest that acid-chlorite pretreatment can
improve the bio-sugar and bioethanol production of CR by removing the phenolic
and brown compounds.
PMID- 28411492
TI - Evaluation of an integrated process to fully utilize bamboo biomass during the
production of bioethanol.
AB - Aiming for the complete utilization of bamboo biomass, an integrated process
which combines ethanol production with the recovery of silica and lignin was
proposed. To reduce chemical charge required for the fractionation of silica and
lignin from bamboo and improve the digestibility of the obtained substrate, a
sequentially two-stage pretreatment process of autohydrolysis and alkaline
extraction was carried out. From the view of enhancing enzymatic hydrolysis and
recovery of silica and lignin, a two-stage treatment of autohydrolysis at 180
degrees C for 90min followed by alkaline extraction at 100 degrees C with 6% NaOH
(based on pretreated chips) for 120min was optimized. About 93.7% of original
silica and 75.7% of original lignin could be recovered from bamboo. Enzymatic
hydrolysis and fermentation of carbohydrates showed that an overall sugar yield
of 88.6% of original sugar content and an ethanol recovery of 0.467g/g sugar were
achieved based on the proposed scheme.
PMID- 28411493
TI - A generalized disjunctive programming framework for the optimal synthesis and
analysis of processes for ethanol production from corn stover.
AB - The aim of this study is to analyze the techno-economic performance of process
configurations for ethanol production involving solid-liquid separators and
reactors in the saccharification and fermentation stage, a family of process
configurations where few alternatives have been proposed. Since including these
process alternatives creates a large number of possible process configurations, a
framework for process synthesis and optimization is proposed. This approach is
supported on kinetic models fed with experimental data and a plant-wide techno
economic model. Among 150 process configurations, 40 show an improved MESP
compared to a well-documented base case (BC), almost all include solid separators
and some show energy retrieved in products 32% higher compared to the BC.
Moreover, 16 of them also show a lower capital investment per unit of ethanol
produced per year. Several of the process configurations found in this work have
not been reported in the literature.
PMID- 28411494
TI - Fibroblast growth factor 23 as a predictor of cardiovascular and all-cause
mortality in prospective studies.
AB - BACKGROUND AND AIMS: The prognostic value of fibroblast growth factor 23 (FGF23)
for mortality remains controversial. We performed a meta-analysis of cohort
studies to examine the controversial relationship between FGF23 and mortality.
METHODS: PubMed, EMBASE, the Cochrane Library databases and reference
bibliographies were searched through September 2016 to identify prospective
cohort studies with relative risks (RRs) and 95% confidence intervals (CIs) for
FGF23 and mortality. A random effects model was used to pool the risk estimates.
A dose-response analysis of the risk for all-cause mortality associated with
FGF23 was conducted using the generalized least squares trend estimation method.
RESULTS: Nineteen prospective cohort studies were eligible for inclusion in this
meta-analysis, of which 16 reported all-cause mortality and 9 reported
cardiovascular mortality. During the follow-up periods ranging from 1 to 18.6
years, 5606 deaths occurred among 22,805 participants and 2458 cardiovascular
deaths occurred among 28,845 participants. Elevated FGF23 was associated with an
increased risk of all-cause mortality (RR 1.68; 95% CI 1.48-1.92) and
cardiovascular mortality (RR 1.68; 95% CI 1.38-2.04) with moderate heterogeneity.
These associations were not markedly modified by the geographic location, follow
up length, patient predisposition, FGF23 measurement or study quality. A
sensitivity analysis yielded a similar effect on the pooled risk estimate.
Evidence of a nonlinear relationship between FGF23 and all-cause mortality was
observed in the dose-response analysis, with the risk gradually increasing as
FGF23 increased. CONCLUSIONS: This meta-analysis showed that individuals with
increased plasma FGF23 levels might suffer a higher risk of all-cause mortality
and cardiovascular mortality.
PMID- 28411495
TI - Arbuscular mycorrhiza formation and its function under elevated atmospheric O3: A
meta-analysis.
AB - We quantitatively evaluated the effects of elevated O3 on arbuscular mycorrhiza
(AM) formation and on AM role in promoting plant growth in regard to several
moderating variables (O3 levels, O3 exposure duration, plant types, AM fungi
family, and additional stress) by means of meta-analysis of published data. The
analysis consisted of 117 trials representing 20 peer-reviewed articles and 16
unpublished trials. Relative to non-mycorrhizal controls, AM inoculation did not
significantly alter plant growth (shoot biomass, root biomass, total biomass and
plant height) when O3 concentration was less than 80 ppb, but at concentrations
above 80 ppb symbiosis was associated with increases of 68% in shoot biomass and
131% in root biomass. AM effects on plant growth were affected by the duration of
O3 exposure but did not differ much with AM fungi taxa or plant type. AM
symbiosis has also led to higher yields under O3 stress, relative to the non
mycorrhizal plants, and the AM effects have been more pronounced as O3
concentration increases. As with biomass, AM effects on yield have been affected
by the duration of O3 exposure, with the greatest increase (100%) occurring at 61
90 d. AM-induced promotion of yield differed with fungal species but not with
plant type or other abiotic stress. Colonization of roots by AM fungi has been
negatively affected by elevated O3 compared to ambient O3; total mycorrhizal
colonization rate (MCR), arbuscular MCR, vesicular MCR and hyphal coil MCR
declined as O3 levels rose. AM colonization rates were affected by duration of O3
exposure, plant type, AM fungal taxa and other concurrent stresses in most cases.
The analysis showed that AM inoculation has the potential to ameliorate
detrimental effects of elevated O3 on plant growth and productivity, despite
colonization rates being negatively affected by elevated O3.
PMID- 28411496
TI - Exposure to environmental noise and risk for male infertility: A population-based
cohort study.
AB - BACKGROUND: Noise is associated with poor reproductive health. A number of animal
studies have suggested the possible effects of exposure to high noise levels on
fertility; to date, a little such research has been performed on humans.
OBJECTIVES: We examined an association between daytime and nocturnal noise
exposures over four years (2002-2005) and subsequent male infertility. METHODS:
We used the National Health Insurance Service-National Sample Cohort (2002-2013),
a population-wide health insurance claims dataset. A total of 206,492 males of
reproductive age (20-59 years) with no history of congenital malformations were
followed up for an 8-year period (2006-2013). Male infertility was defined as per
ICD-10 code N46. Data on noise exposure was obtained from the National Noise
Information System. Exposure levels of daytime and night time noise were
extrapolated using geographic information systems and collated with the subjects'
administrative district code, and individual exposure levels assigned. RESULTS:
During the study period, 3293 (1.6%) had a diagnosis of infertility. Although
there was no association of infertility with 1-dB increments in noise exposure, a
non-linear dose-response relationship was observed between infertility and
quartiles of daytime and night time noise after adjustment for confounding
variables (i.e., age, income, residential area, exercise, smoking, alcohol
drinking, blood sugar, body mass index, medical histories, and particulate
pollution). Based on WHO criteria, adjusted odds for infertility were
significantly increased (OR = 1.14; 95% CI, 1.05-1.23) in males exposed to night
time noise >= 55 dB. CONCLUSION: We found a significant association between
exposure to environmental noise for four years and the subsequent incidence of
male infertility, suggesting long-term exposure to noise has a role in
pathogenesis of male infertility.
PMID- 28411497
TI - Chlorpyrifos-induced oxidative damage is reduced under warming and predation
risk: Explaining antagonistic interactions with a pesticide.
AB - Interactions with pollutants and environmental factors are poorly studied for
physiological traits. Yet physiological traits are important for explaining and
predicting interactions at higher levels of organization. We investigated the
single and combined impact of the pesticide chlorpyrifos, predation risk and
warming on endpoints related to oxidative stress in the damselfly Enallagma
cyathigerum. We thereby integrated information on reactive oxygen species (ROS),
antioxidant enzymes and oxidative damage. All three treatments impacted the
oxidative stress levels and for most traits the pesticide interacted
antagonistically with warming or predation risk. Chlorpyrifos exposure resulted
in increased ROS levels, decreased antioxidant defence and increased oxidative
damage compared to the control situation. Under warming, the pesticide-induced
increase in oxidative stress was less strong and the investment in antioxidant
defence higher. Although both the pesticide and predation risk increased
oxidative damage, the effects of the pesticide on oxidative damage were less
strong in the presence of predator cues (at 20 degrees C). Despite the weaker
pesticide-induced effects under predation risk, the combination of the pesticide
and predator cues consistently caused the highest ROS levels, the lowest
antioxidant defence and the highest oxidative damage, indicating the importance
of cumulative stressor effects for impairing fitness. Our results provide the
first evidence for antagonistic interactions of warming and predation risk with a
pollutant for physiological traits. We identified two general mechanisms that may
generate antagonistic interactions for oxidative stress: cross-tolerance and the
maximum cumulative levels of damage.
PMID- 28411498
TI - A pilot study on the association between rare earth elements in maternal hair and
the risk of neural tube defects in north China.
AB - Rare earth elements (REEs) have many applications in industry, agriculture, and
medicine, resulting in occupational and environmental exposure and concerns
regarding REE-associated health effects. However, few epidemiological studies
have examined the adverse effects of REEs on pregnancy outcomes. Therefore, this
study examined the relationship between the REE concentrations in maternal hair
growing during early pregnancy and the risk of neural tube defects (NTDs) in
offspring. We included 191 women with NTD-affected pregnancies (cases) and 261
women delivering healthy infants (controls). The cases were divided into three
subtypes: anencephaly, spina bifida, and encephalocele. Four REEs in maternal
hair were analyzed by inductively coupled plasma-mass spectrometry: lanthanum
(La), cerium (Ce), praseodymium (Pr), and neodymium (Nd). A questionnaire was
used to collect information about maternal sociodemographic characteristics and
dietary habits. The median concentrations of Ce and Pr in the NTD group were
higher than those in the control group, whereas there were no significant
differences for La and Nd. The adjusted odds ratios (ORs) for the four REE
concentrations above the median in the case groups were not significantly > 1. An
increasing frequency of the consumption of beans or bean products and fresh fruit
was negatively correlated with the four REE concentrations. Our results did not
suggest that the concentrations of REEs in maternal hair were associated with the
risk of NTDs or any subtype of NTDs in the general population.
PMID- 28411499
TI - Characteristics and environmental fate of the anionic surfactant sodium lauryl
ether sulphate (SLES) used as the main component in foaming agents for mechanized
tunnelling.
AB - The anionic surfactant sodium lauryl ether sulphate (SLES) is the main component
of most commercial products used for soil conditioning in the excavation
industry, in particular as lubricants for mechanized tunnelling. Its use during
the excavation processes can result in either the subsequent possible re-use of
the huge amount of soil debris as by-products (e.g. land covering) or its
discharge as waste. Currently, there are neither SLES soil threshold limits in
European legislation, nor comprehensive studies on the environmental risk for
soil ecosystems in these exposure scenarios. In this context, the present paper
reviews the available data on the intrinsic characteristics of persistence and
the ecotoxicological effects of the anionic surfactant SLES. Although SLES is
generally reported to be biodegradable in standard tests, with degradation rates
between 7 h and 30 days, depending on the initial conditions, data on its
biodegradation in environmental studies are quite scarce. Consequently, assessing
SLES biodegradation rates in field conditions is crucial for evaluating if in
residual concentrations (typically in the range 40-500 mg/kg in excavated soils)
it can or not be a potential hazard for terrestrial and water organisms.
Laboratory ecotoxicological tests pointed out detrimental effects of SLES for
aquatic organisms, while data on the terrestrial species are rather poor so far
and further studies at the expected environmental concentrations are necessary.
Finally, the review reports the main analytical methods available for detecting
anionic surfactants in solid matrices and the future research needed to improve
knowledge on the possible environmental risks posed by the use of SLES in foaming
agents for mechanized tunnelling.
PMID- 28411500
TI - Computerized reconstruction of fragmentary skeletal remains.
AB - This research presents a new software, "Fragmento", for accurate analyses of
fragmentary human skeletal remains and facilitation of three-dimensional (3D)
fragmentary matching and full bone reconstruction. The framework utilizes the
power of statistical bone atlases to create 3D templates for bone matching and to
interpolate missing anatomy for full bone reconstruction. Developed tool has
enhanced features allowing the user to visualize, review and scale all scanned
skeletal remains within a 3D statistical template, merging accepted registered
elements to provide a fully reconstructed bone. A three stage validation was
performed on Fragmento: Stages I and II used simulated fragmentary data which was
compared to full bones with an error less than 3mm; Stage III compared output
from geographic information system (GIS) software with comparable results. This
validation process demonstrates the robustness and utility of Fragmento as tool
for 3D fragmentary bone matching and full bone reconstruction.
PMID- 28411501
TI - Different cross protection scopes of two avian influenza H5N1 vaccines against
infection of layer chickens with a heterologous highly pathogenic virus.
AB - Avian influenza (AI) virus strains vary in antigenicity, and antigenic
differences between circulating field virus and vaccine virus will affect the
effectiveness of vaccination of poultry. Antigenic relatedness can be assessed by
measuring serological cross-reactivity using haemagglutination inhibition (HI)
tests. Our study aims to determine the relation between antigenic relatedness
expressed by the Archetti-Horsfall ratio, and reduction of virus transmission of
highly pathogenic H5N1 AI strains among vaccinated layers. Two vaccines were
examined, derived from H5N1 AI virus strains A/Ck/WJava/Sukabumi/006/2008 and
A/Ck/CJava/Karanganyar/051/2009. Transmission experiments were carried out in
four vaccine and two control groups, with six sets of 16 specified pathogen free
(SPF) layer chickens. Birds were vaccinated at 4weeks of age with one strain and
challenge-infected with the homologous or heterologous strain at 8weeks of age.
No transmission or virus shedding occurred in groups challenged with the
homologous strain. In the group vaccinated with the Karanganyar strain, high
cross-HI responses were observed, and no transmission of the Sukabumi strain
occurred. However, in the group vaccinated with the Sukabumi strain, cross-HI
titres were low, virus shedding was not reduced, and multiple transmissions to
contact birds were observed. This study showed large differences in cross
protection of two vaccines based on two different highly pathogenic H5N1 virus
strains. This implies that extrapolation of in vitro data to clinical protection
and reduction of virus transmission might not be straightforward.
PMID- 28411502
TI - Characteristics of Diogenes syndrome.
PMID- 28411503
TI - Anatomical distance affects cortical-subcortical connectivity in first-episode,
drug-naive somatization disorder.
AB - BACKGROUND: Brain structural and functional alterations in the cortical
subcortical circuits have been observed in somatization disorder (SD). However,
whether and how anatomical distance affects the cortical-subcortical connectivity
in SD remain unclear. This study aims to examine whether anatomical distance
affects the cortical-subcortical in first-episode, drug-naive SD. METHODS: Twenty
five first-episode, drug-naive patients with SD and twenty-eight healthy controls
were recruited for a resting-state scan. Regional functional connectivity
strength (FCS) was calculated for each voxel in the brain, which was further
divided into short- and long-range FCSs. Correlation analyses were conducted
between abnormal FCS and clinical/cognitive variables in the patients. RESULTS:
Compared with the controls, the patients showed increased short-range positive
FCS (spFCS) in the right superior frontal gyrus (SFG) and decreased spFCS in the
left pallidum, and increased long-range positive FCS (lpFCS) in the left middle
frontal gyrus and right inferior temporal gyrus (ITG). Positive correlations were
observed between the spFCS values in the right SFG and Eysenck Personality
Questionnaire psychoticism scores (r=0.441, p=0.027, uncorrected) and between the
lpFCS values in the right ITG and scores of digit symbol-coding of Wechsler Adult
Intelligence Scale (r=0.416, p=0.039, uncorrected) in the patients CONCLUSIONS:
The patients exhibited increased spFCS/lpFCS in the cortical regions and
decreased spFCS in the subcortical regions. The left pallidum is first reported
here to show decreased spFCS in SD. The present results suggest that abnormal
cortical-subcortical circuits may play an important role in SD neurobiology.
PMID- 28411504
TI - Severe insomnia is associated with hypertriglyceridemia in women with major
depression treated in psychiatry settings.
AB - BACKGROUND: Hypertriglyceridemia (HTG) is a cardiovascular risk factor. In the
general population, elevated fasting triglyceridemia (TG) is associated with
insomnia. Since insomnia is a core symptom of Major Depressive Episodes (MDE), we
studied the association of severe insomnia with HTG in major depression. METHODS:
We used the baseline data of the METADAP cohort, comprising 624 patients with a
current MDE in a context of Major Depressive Disorder treated in psychiatry
settings, without current alcohol use disorders. Patients were screened for
severe insomnia, defined by a score of four or more on the three Hamilton
Depression Rating Scale (HDRS) sleep items, and for HTG characterised by
TG>=200mg/dL. RESULTS: Severe insomnia was observed in 335(54%) patients with a
current MDE, of whom 234(70%) were women; 49(8%) patients had HTG, of whom
25(51%) were women. 69(11%) patients were treated with lipid-lowering drugs.
Severe insomnia was associated with a higher frequency of HTG in the whole sample
(9.9% vs 5.6%, p=0.046) and in the subgroup of women (9.0% vs 2.0%, p=0.002).
Multivariate logistic regression analyses adjusted for age, education levels, BMI
and total HDRS scores confirmed the association between severe insomnia and HTG
in the whole sample (OR=2.02, 95%CI [1.00-4.08], p=0.05) as well as in the
subgroup of women (OR=4.82, 95%CI [1.5-15.5], p=0.008). No association was shown
in men. PERSPECTIVES: HTG should be systematically investigated in depressed
patients with severe insomnia and particularly in women. Further studies are
needed to explain the association we observed between severe insomnia and HTG.
PMID- 28411505
TI - Heterogeneity of emotional and interpersonal difficulties in alcohol-dependence:
A cluster analytic approach.
AB - BACKGROUND: Emotional and interpersonal impairments have been largely reported in
alcohol-dependence, and their role in its development and maintenance is widely
established. However, earlier studies have exclusively focused on group
comparisons between healthy controls and alcohol-dependent individuals,
considering them as a homogeneous population. The variability of socio-emotional
profiles in this disorder thus remains totally unexplored. The present study used
a cluster analytic approach to explore the heterogeneity of affective and social
disorders in alcohol-dependent individuals. METHODS: 296 recently-detoxified
alcohol-dependent patients were first compared with 246 matched healthy controls
regarding self-reported emotional (i.e. alexithymia) and social (i.e.
interpersonal problems) difficulties. Then, a cluster analysis was performed,
focusing on the alcohol-dependent sample, to explore the presence of differential
patterns of socio-emotional deficits and their links with demographic,
psychopathological and alcohol-related variables. RESULTS: The group comparison
between alcohol-dependent individuals and controls clearly confirmed that
emotional and interpersonal difficulties constitute a key factor in alcohol
dependence. However, the cluster analysis identified five subgroups of alcohol
dependent individuals, presenting distinct combinations of alexithymia and
interpersonal problems ranging from a total absence of reported impairment to
generalized socio-emotional difficulties. CONCLUSIONS: Alcohol-dependent
individuals should no more be considered as constituting a unitary group
regarding their affective and interpersonal difficulties, but rather as a
population encompassing a wide variety of socio-emotional profiles. Future
experimental studies on emotional and social variables should thus go beyond mere
group comparisons to explore this heterogeneity, and prevention programs
proposing an individualized evaluation and rehabilitation of these deficits
should be promoted.
PMID- 28411506
TI - The ten-year course of depression in primary care and long-term effects of
psychoeducation, psychiatric consultation and cognitive behavioral therapy.
AB - BACKGROUND: While the majority of depressed patients are treated in primary care,
long-term follow-up data on the naturalistic course of depression and treatment
effectiveness in this setting are scarce. This study examined the ten-year course
of depression in primary care patients who had participated in a randomized
clinical trial aiming at enhancement of depression outcomes. METHODS: Of the
original sample (n=267), 166 patients participated in the ten-year follow-up;
missingness was random. Four treatments were compared: (1) Care As Usual (CAU;
n=51); (2) a Psychoeducational Prevention program (PEP; n=68); (3) Psychiatric
Consultation followed by PEP (PC+PEP; n=21); and (4) brief Cognitive Behavioral
Therapy followed by PEP (CBT+PEP; n=26). During the first three years interviews
based on the Composite International Diagnostic Interview (CIDI) were three
monthly applied, the seven years thereafter were assessed with a once applied
CIDI and a face-to-face life chart-based interview. RESULTS: During the ten-year
follow-up 76.5% of the patients developed a new depressive episode, 83.4% used
antidepressants (median usage 3.1 years), median depression diagnosis-free time
was 9.0 years, and median residual symptom-free time 3.8 years. Treatments did
not significantly differ on these outcomes, only trends appeared for lower
depression severity for CBT+PEP, and, along with PEP, a higher proportion of
symptom-free time. LIMITATIONS: Assessment with the once applied life chart
interview (a valid and reliable instrument) is less precise than the three
monthly assessments during the first three years. CONCLUSIONS: The long-term
course of depression in primary care is unfavorable, whereas treatment effects
over time seem absent or small.
PMID- 28411507
TI - Bipolar mixed features - Results from the comparative effectiveness for bipolar
disorder (Bipolar CHOICE) study.
AB - BACKGROUND: DSM-5 changed the criteria from DSM-IV for mixed features in mood
disorder episodes to include non-overlapping symptoms of depression and
hypomania/mania. It is unknown if, by changing these criteria, the same group
would qualify for mixed features. We assessed how those meeting DSM-5 criteria
for mixed features compare to those meeting DSM-IV criteria. METHODS: We analyzed
data from 482 adult bipolar patients in Bipolar CHOICE, a randomized comparative
effectiveness trial. Bipolar diagnoses were confirmed through the MINI
International Neuropsychiatric Interview (MINI). Presence and severity of mood
symptoms were collected with the Bipolar Inventory of Symptoms Scale (BISS) and
linked to DSM-5 and DSM-IV mixed features criteria. Baseline demographics and
clinical variables were compared between mood episode groups using ANOVA for
continuous variables and chi-square tests for categorical variables. RESULTS: At
baseline, the frequency of DSM-IV mixed episodes diagnoses obtained with the MINI
was 17% and with the BISS was 20%. Using DSM-5 criteria, 9% of participants met
criteria for hypomania/mania with mixed features and 12% met criteria for a
depressive episode with mixed features. Symptom severity was also associated with
increased mixed features with a high rate of mixed features in patients with
mania/hypomania (63.8%) relative to those with depression (8.0%). LIMITATIONS:
Data on mixed features were collected at baseline only and thus do not reflect
potential patterns in mixed features within this sample across the study
duration. CONCLUSIONS: The DSM-5 narrower, non-overlapping definition of mixed
episodes resulted in fewer patients who met mixed criteria compared to DSM-IV.
PMID- 28411508
TI - Interventions to support people with dementia and their caregivers during the
transition from home care to nursing home care: A systematic review.
AB - BACKGROUND: During the transition of people with dementia from home to nursing
home family caregivers often feel burdened. OBJECTIVES: We aimed to 1) identify
interventions which support people with dementia and their caregivers in the
transition from home care to nursing home care, 2) synthesize the evidence for
efficacy of these interventions, and 3) examine whether the identified
interventions have been systematically developed, evaluated and implemented
according to the Medical Research Council guidance on complex interventions.
DESIGN: A systematic review of randomised controlled trials was conducted
according to the recommendations specified in the Cochrane Handbook for
Intervention Reviews. The review protocol was registered in PROSPERO (2015:
CRD42015019839). Reporting follows the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses: the PRISMA statement. DATA SOURCES: MEDLINE, CENTRAL,
PsycINFO, CINAHL, OTseeker, and PEDro, were searched. Other sources included
Google Scholar, and ALOIS. REVIEW METHODS: Two reviewers independently assessed
the eligibility of the articles. Data extraction was performed by one reviewer
and verified independently by another. The Cochrane Risk of Bias tool was used
for critical appraisal. Development and evaluation of the identified
interventions were assessed, taking the Medical Research Council guidance into
account. Review findings were synthesized narratively. RESULTS: The search
yielded 1278 records. Five studies were included, all conducted in the United
States (4 RCTs and 1 cRCT with a total of 695 participants). The psychosocial
interventions were individual and family counseling via telephone or ad hoc all
of which addressed only informal caregivers. The intervention components, content
and mode of delivery differed widely with inconsistent results. Significant
intervention effects were found for the reduction of caregivers' depressive
symptoms, burden, feeling of guilt, emotional distress, overload, and
interactions with staff. Other outcomes, i.e. stress, placement adaptation, role
overload, and role captivity, were not statistically significantly affected. The
assessment for bias risk across studies varied from moderate to low. Only two
studies tested the feasibility of the intervention before full scale evaluation,
none evaluated the implementation process according to the Medical Research
Council framework. CONCLUSIONS: We identified only a few studies with
heterogeneous outcomes; evidence regarding the effectiveness of psychosocial
interventions is thus insufficient. Further research is needed focusing on the
development and evaluation of complex psychosocial interventions and more well
designed RCTs with larger sample sizes based on a rigorous methodology. Reporting
on feasibility and implementation processes of interventions should be
guaranteed, since it is crucial to evaluate transferability across care settings.
PMID- 28411510
TI - Compressed sensing for STEM tomography.
AB - A central challenge in scanning transmission electron microscopy (STEM) is to
reduce the electron radiation dosage required for accurate imaging of 3D
biological nano-structures. Methods that permit tomographic reconstruction from a
reduced number of STEM acquisitions without introducing significant degradation
in the final volume are thus of particular importance. In random-beam STEM (RB
STEM), the projection measurements are acquired by randomly scanning a subset of
pixels at every tilt view. In this work, we present a tailored RB-STEM
acquisition-reconstruction framework that fully exploits the compressed sensing
principles. We first demonstrate that RB-STEM acquisition fulfills the
"incoherence" condition when the image is expressed in terms of wavelets. We then
propose a regularized tomographic reconstruction framework to recover volumes
from RB-STEM measurements. We demonstrate through simulations on synthetic and
real projection measurements that the proposed framework reconstructs high
quality volumes from strongly downsampled RB-STEM data and outperforms existing
techniques at doing so. This application of compressed sensing principles to STEM
paves the way for a practical implementation of RB-STEM and opens new
perspectives for high-quality reconstructions in STEM tomography.
PMID- 28411509
TI - Direct-acting antivirals and host-targeting strategies to combat enterovirus
infections.
AB - Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus
D68, rhinovirus) include many human pathogens causative of various mild and more
severe diseases, especially in young children. Unfortunately, antiviral drugs to
treat enterovirus infections have not been approved yet. Over the past decades,
several direct-acting inhibitors have been developed, including capsid binders,
which block virus entry, and inhibitors of viral enzymes required for genome
replication. Capsid binders and protease inhibitors have been clinically
evaluated, but failed due to limited efficacy or toxicity issues. As an
alternative approach, host-targeting inhibitors with potential broad-spectrum
activity have been identified. Furthermore, drug repurposing screens have
recently uncovered promising new inhibitors with disparate viral and host
targets. Together, these findings raise hope for the development of (broad-range)
anti-enteroviral drugs.
PMID- 28411511
TI - Elevated CO2 and salinity are responsible for phenolics-enrichment in two
differently pigmented lettuces.
AB - Both salt stress and high CO2 level, besides influencing secondary metabolism,
can affect oxidative status of plants mainly acting in an opposite way with
salinity provoking oxidative stress and elevated CO2 alleviating it. The aim of
the present work was to study the changes in the composition of phenolic acids
and flavonoids as well as in the antioxidant activity in two differently
pigmented lettuce cvs (green or red leaf) when submitted to salinity (200 mM
NaCl) or elevated CO2 (700 ppm) or to their combination in order to evaluate how
a future global change can affect lettuce quality. Following treatments, the red
cv. always maintained higher levels of antioxidant secondary metabolites as well
as antioxidant activity, proving to be more responsive to altered environmental
conditions than the green one. Overall, these results suggest that the
application of moderate salinity or elevated CO2, alone or in combination, can
induce the production of some phenolics that increase the health benefits of
lettuce. In particular, moderate salinity was able to induce the synthesis of the
flavonoids quercetin, quercetin-3-O-glucoside, quercetin-3-O-glucuronide and
quercitrin. Phenolics-enrichment as well as a higher antioxidant capacity were
also observed under high CO2 with the red lettuce accumulating cyanidin, free
chlorogenic acid, conjugated caffeic and ferulic acid as well as quercetin,
quercetin-3-O-glucoside, quercetin-3-O-glucuronide, luteolin-7-O-glucoside,
rutin, quercitrin and kaempferol. When salinity was present in combination with
elevated CO2, reduction in yield was prevented and a higher presence of phenolic
compounds, in particular luteolin, was observed compared to salinity alone.
PMID- 28411512
TI - Evaluating biochemical response of filamentous algae integrated with different
water bodies.
AB - The present study prompted the second attempts to evaluate biochemical responses
of filamentous algae under different physico-chemical variables in various water
bodies in Turkey. These variables were investigated by use of multivariate
approach in the years of 2013 (May and November) and 2014 (May and October).
Studied ecoregions had the different geographic position, climate, land-use, and
anthropogenic activities, could strongly affect physico-chemical variables of
water bodies, which caused to change or regulate in algal biomass composition due
to the different response of filamentous species. Besides, biochemical responses
of species changed at different sampling times and stations. Multivariate
analyses indicated that temperature, heavy metals, and nutrient contents of
aquatic systems were found to be major variables driving the spatial and temporal
occurrence and biochemical contents of filamentous species. Total protein and
pigment production by filamentous algae were high in water bodies having high
nutrients, whereas they were low in high heavy metal contents. Amount of
malondialdehyde (MDA), H2O2, total thiol group, total phenolic compounds,
proline, total carbohydrate, and bioaccumulation of metals by filamentous algae
were closely related with heavy metal contents of water bodies, indicated by the
multivariate approach. Significant increase in aforementioned biochemical
compounds with a distinct range of habitats and sensitive-tolerance to
environmental conditions could make them highly valuable indicators.
PMID- 28411513
TI - Contamination, source identification, and risk assessment of polycyclic aromatic
hydrocarbons in the soils of vegetable greenhouses in Shandong, China.
AB - The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were analyzed in
soil (n=196) and vegetable (n=30) collected from greenhouses, and also in the
soil (n=27) collected from agriculture fields close to the greenhouses in
Shandong Province, China. The total PAH concentration (?16PAH) ranged from
152.2ug/kg to 1317.7ug/kg, within the moderate range in agricultural soils of
China. Three-ring PAHs were the dominant species, with Phe (16.3%), Ace (13.1%),
and Fl (10.5%) as the major compounds. The concentrations of low molecular weight
(LMW <=3 rings) PAHs were high in the east and north of Shandong, while the
concentrations of high molecular weight (HMW >=4 rings) PAHs were high in the
south and west of the study area. The PAH level in soils in industrial areas (IN)
was higher than those in transport areas (TR) and rural areas (RR). No
significant difference in concentration of ?16PAH and composition was observed in
soils of vegetable greenhouses and field soils. PAH concentration exhibited a
weakly positive correlation with alkaline nitrogen, available phosphorus in soil,
but a weakly negative correlation with soil pH. However, no obvious correlation
was observed between PAH concentration and organic matter of soil, or ages of
vegetable greenhouses. ?16PAH in vegetables ranged from 89.9ug/kg to 489.4ug/kg,
and LMW PAHs in vegetables positively correlated with those in soils. The sources
of PAHs were identified and quantitatively assessed through positive matrix
factorization. The main source of PAHs in RR was coal combustion, while the
source was traffic in TR and IN. Moreover, petroleum source, coke source, biomass
combustion, or mixed sources also contributed to PAH pollution. According to
Canadian soil quality guidelines, exposure to greenhouse soils in Shandong posed
no risk to human health.
PMID- 28411514
TI - Cylindrospermopsin induced changes in growth, toxin production and antioxidant
response of Acutodesmus acuminatus and Microcystis aeruginosa under differing
light and nitrogen conditions.
AB - Growing evidence suggests that some bioactive metabolites (e.g. cyanotoxins)
produced by cyanobacteria have allelopathic potential, due to their inhibitory or
stimulatory effects on competing species. Although a number of studies have shown
that the cyanotoxin cylindrospermopsin (CYN) has variable effects on
phytoplankton species, the impact of changing physicochemical conditions on its
allelopathic potential is yet to be investigated. We investigated the
physiological response of Microcystis aeruginosa (Cyanobacteria) and Acutodesmus
acuminatus (Chlorophyta) to CYN under varying nitrogen and light conditions. At
24h, higher microcystins content of M. aeruginosa was recorded under limited
light in the presence of CYN, while at 120h the lower levels of the toxins were
observed in the presence of CYN under optimum light. Total MCs concentration was
significantly (p<0.05) lowered by CYN after 120h of exposure under limited and
optimum nitrogen conditions. On the other hand, there were no significant
(p>0.05) changes in total MCs concentrations after exposure to CYN under high
nitrogen conditions. As expected, limited light and limited nitrogen conditions
resulted in lower cell density of both species, while CYN only significantly
(p<0.05) inhibited the growth of M. aeruginosa. Regardless of the light or
nitrogen condition, the presence of CYN increased internal H2O2 content of both
species, which resulted in significant (p<0.05) changes in antioxidant enzyme
(catalase, peroxidase, superoxide dismutase and glutathione S-transferase)
activities. The oxidative stress caused by CYN was higher under limited light and
limited nitrogen. These results showed that M. aeruginosa and A. acuminatus have
variable response to CYN under changing light and nitrogen conditions, and
demonstrate that need to consider changes in physicochemical conditions during
ecotoxicological and ecophysiological investigations.
PMID- 28411515
TI - Response of soil microbial activities and microbial community structure to
vanadium stress.
AB - High levels of vanadium (V) have long-term, hazardous impacts on soil ecosystems
and biological processes. In the present study, the effects of V on soil
enzymatic activities, basal respiration (BR), microbial biomass carbon (MBC), and
the microbial community structure were investigated through 12-week greenhouse
incubation experiments. The results showed that V content affected soil
dehydrogenase activity (DHA), BR, and MBC, while urease activity (UA) was less
sensitive to V stress. The average median effective concentration (EC50)
thresholds of V were predicted using a log-logistic dose-response model, and they
were 362mgV/kg soil for BR and 417mgV/kg soil for DHA. BR and DHA were more
sensitive to V addition and could be used as biological indicators for soil V
pollution. According to a polymerase chain reaction-denaturing gradient gel
electrophoresis (PCR-DGGE) analysis, the structural diversity of the microbial
community decreased for soil V contents ranged between 254 and 1104mg/kg after 1
week of incubation. As the incubation time increased, the diversity of the soil
microbial community structure increased for V contents ranged between 354 and
1104mg/kg, indicating that some new V-tolerant bacterial species might have
replicated under these conditions.
PMID- 28411516
TI - Effects of foliar dressing of selenite and silicate alone or combined with
different soil ameliorants on the accumulation of As and Cd and antioxidant
system in Brassica campestris.
AB - This study was conducted to investigate the possibility of using a combined
technology to synchronously reduce As and Cd accumulation in the edible parts of
Brassica campestris. The results showed that a foliar application of selenite
(Se) and silicon (Si) combined with soil ameliorants (including Ca-Mg-P
fertilizer, sodium silicate and red mud) showed limited effects on the growth of
B. campestris. The As concentration in the leaves of B. campestris in all
treatments was below the Chinese safety standard. When sodium silicate and Ca-Mg
P fertilizer were added to the soil, the additional foliar application of Se and
Si could in some cases help further reduce the concentrations of As and Cd in the
leaves of B. campestris. However, when red mud was applied to the soil, the
foliar application of Se and Si enhanced the Cd concentration in the leaves of B.
campestris. In most cases, high levels of soil ameliorants plus foliar
application of Se and Si significantly enhanced the As concentrations in both the
soil solution and the roots of B. campestris but reduced the soil solution Cd
concentration and the leaf As concentration. Most of the treatments reduced the
thiobarbituric acid reactive substances (TBARS) concentration in the leaves of B.
campestris, and the foliar application of Se and Si helped the soil ameliorants
alleviate the oxidative stress resulting from As and Cd exposure. In this study,
several treatments significantly increased the activities of superoxide dismutase
(SOD) and ascorbate peroxidase (APX). However, the enzymes peroxidase (POD) and
catalase (CAT) were not induced by most treatments. In summary, the combined
treatment of 1gkg-1 Ca-Mg-P fertilizer plus foliar spraying 2mmolL-1 sodium
selenite was most effective in reducing the Cd concentration and a rather strong
ability to reduce the As concentration and trigger the activities of SOD and APX
in the leaves of B. campestris.
PMID- 28411517
TI - Pre- and post-surgical psychiatric assessments and intervention by major epilepsy
centers in Japan - Nationwide survey.
AB - BACKGROUND: Although psychiatric issues following epilepsy surgery are now widely
recognized as a major problem, actual awareness of these issues by epilepsy
centers remains to be elucidated. This is the first known report regarding the
use of psychiatric assessments and interventions by epilepsy centers throughout
Japan. PARTICIPANTS AND METHODS: At the beginning of 2016, we sent a
questionnaire regarding psychiatric assessments performed before and after
epilepsy surgery, psychiatric intervention after surgery, and future plans for
dealing with psychiatric issues in relation to epilepsy surgery, which consisted
of a total of 24 items, to all members of the Japan Epilepsy Center Association
(JEPICA). Nearly all major epilepsy centers in Japan are included in JEPICA,
which had 31 members in 2016. Twenty-four (77%) of the 31 centers responded to
the questionnaire. RESULTS: Seventeen (70.8%) centers answered that a
psychiatrist was incorporated as part of their epilepsy surgery unit. In
addition, 17 (70.8%) noted that psychiatric assessments were obtained prior to
surgery, which were performed by psychiatrists in 8 (33.3%) centers and
psychologists in 11 (45.8%). In 23 (95.8%) of the centers, the risk of occurrence
of psychiatric illness following surgery was routinely explained prior to
surgery, at least to surgical candidates with high susceptibility. In total,
cases of psychiatric illness following surgery had been experienced in 16 (66.7%)
centers, with depression as the most commonly encountered (41.7%), followed by
anxiety (33.3%), psychosis (25.0%), and psychogenic non-epileptic seizures
(8.3%). DISCUSSION: Strong points of epilepsy centers in Japan include serious
concern regarding post-surgical psychiatric illness by nearly all members of
JEPICA and explanation of the risk of psychiatric adverse events provided
beforehand to their patients. On the other hand, the small size of some epilepsy
centers, along with lack of a standardized method for evaluation of psychiatric
symptoms as well as dependence on the individual willingness of psychiatrists
assigned as members of the epilepsy units, seem to have led to significant
diagnostic and therapeutic gaps among epilepsy centers regarding psychiatric
issues related to epilepsy surgery.
PMID- 28411518
TI - How do you exercise with epilepsy? Insights into the barriers and adaptations to
successfully exercise with epilepsy.
AB - Exercise has been shown to be a physiological and psychological benefit for
people with epilepsy (PWE). However, barriers prevent many PWE from exercising
safely and confidently. This research explored current perceived barriers to
exercise and adaptation techniques used by PWE in order to maintain physical
activity levels. Three focus groups (2-3 participants per group) and three semi
structured interviews were conducted (11 participants total). Constructive
grounded theory was used to frame the study and analyse the findings, presenting
new insight into the motivation, perceived barriers, and adaptation techniques
used to exercise. The main motivator to maintain physical activity levels was the
benefit of exercise on physical and mental health. This was shown in an increase
in mood, higher social interaction, and perceived improvement in overall physical
health as a result of exercise. Current barriers to exercise included a fear of
injury, lack of social support, and exercise-induced seizures (e.g., through
overheating and/or high exercise intensity level). Adaptation techniques used
were self-monitoring through the use of technology, reducing exercise frequency
and intensity level, and exercising at certain times of the day. The importance
of social support was shown to provide increased confidence and positive
encouragement to exercise, contrasting with family and friends worrying for
his/her safety and medical professionals requesting termination of some physical
activities. These findings provide new insight into current adaptation techniques
that are used and developed by PWE to overcome common barriers to exercise. These
new additions to the literature can lead to further development of such
techniques as well as examine current medical professionals' knowledge of the
benefits of exercise for PWE.
PMID- 28411519
TI - 'Breaking Good News': Neurologists' experiences of discussing SUDEP with patients
in Scotland.
AB - Since the findings of a Fatal Accident Inquiry (FAI) in 2010, clinicians working
in Scotland have been advised to discuss the risk of Sudden Unexpected Death in
Epilepsy (SUDEP) with patients immediately or soon after a diagnosis of epilepsy
is made. A thematic analysis was used to describe the experiences discussing
SUDEP of 10 clinicians (six Consultant Neurologists and four Neurology
Registrars) working in Scotland. Contrary to previous research, clinicians appear
to be routinely discussing SUDEP in a standardized fashion with newly diagnosed
patients and the FAI appears to have instigated this change in practice.
Clinicians are ambivalent about the practice and whether this is a Breaking Bad
News (BBN) experience. Clinicians appear to anticipate that patients will be
anxious or distressed discussing SUDEP, despite their experiences that patients
do not react this way. There are further concerns that the pressure to discuss
SUDEP, as a result of the FAI, hinders effective communication of the SUDEP
message. Implications for guideline development are discussed.
PMID- 28411520
TI - The relationship between mood disorder and insomnia depends on race in US
veterans with epilepsy.
AB - PURPOSE: Few data exist on race, medical/psychiatric comorbidities, and insomnia
symptoms in US veterans with epilepsy. Our aims were to examine 1) whether
insomnia symptom prevalence was different between Black and White veterans and 2)
whether predictors of insomnia symptoms varied by race. METHODS: This
retrospective, cross-sectional study included veterans evaluated in an epilepsy
clinic over the course of 1.5years. Individuals completed standardized
assessments for epilepsy and sleep complaints. Insomnia criteria were met by 1)
report of difficulty with sleep initiation, maintenance, or premature awakenings
accompanied by daytime impairment or 2) sedative-hypnotic use on most days of the
month. Demographics, medical/psychiatric comorbidities, and medications were
determined per electronic medical record review. Hierarchical multivariable
logistic regression analyses were performed to determine if race, medical/mental
health comorbidities, and the potential interaction of race with each comorbid
condition were associated with insomnia. RESULTS: Our sample consisted of 165
veterans (32% Black). The unadjusted prevalence of insomnia was not different
between Black and White veterans (42% vs 39%, p=0.68). In adjusted analyses, the
association between mood disorder and insomnia varied by race. Depressed White
veterans had over 11-times higher predicted odds of insomnia (OR 11.4, p<0.001)
than non-depressed White veterans, while depressed Black veterans had 4-times
higher predicted odds of insomnia (OR 4.1, p=0.06) than non-depressed Black
veterans. Although mood disorder diagnosis was associated with insomnia for both
racial groups, White veterans had a stronger association between mood disorder
diagnosis and insomnia than Black veterans. CONCLUSIONS: The relationship between
mood disorder diagnosis and insomnia was stronger for White than Black veterans
with epilepsy. Future studies are needed to explore mental health symptoms and
psychosocial determinants of insomnia with larger samples of minority individuals
with epilepsy.
PMID- 28411521
TI - The experience of epilepsy in later life: A qualitative exploration of illness
representations.
AB - The objective of this study was to explore how older people living with epilepsy
appraise their condition through their lived-experience. The common-sense model
of illness representations (CSMIR) provides a framework to explain how
individuals make sense of and manage health threats. Semi-structured in-depth
interviews based on the CSMIR were conducted with ten people with epilepsy who
were above the age of 65. The results were analyzed using Interpretative
Phenomenological Analysis. Three overarching themes emerged from the analysis:
'the power of epilepsy', 'they say you can live a normal life but you can't' and
'attempts to adjust and cope'. Epilepsy was described as a threatening,
persistent, and unpredictable condition associated with distressing experiences.
Participants described a process of balancing negative psychosocial consequences
including stigma, loss of control, and reliance on other people and medication
with parallel co-existing coping strategies. These attempts to manage the
condition were characterized by a desire for acceptance and increased awareness
of epilepsy, strategies to restore loss of control, and strength derived from
supportive relationships. We conclude that there is large scope for psychosocial
interventions in healthcare provision for this patient group. The roles of
specialist nursing, relationship-centered models, psychotherapy, educational, and
self-management programs are highlighted.
PMID- 28411522
TI - Breaking the age barrier: Epilepsy surgery in septuagenarians.
AB - Resective epilepsy surgery (RES) has traditionally been offered to young patients
(<50years). The reservation about offering RES to the elderly is multifactorial
with their advanced age and comorbidities being the primary reason. The elderly
age group (>=65years of age) is one of the fastest growing populations. The
arbitrary age limits for RES need reconsideration in the face of an ever
increasing elderly population. Considering such changes in demographics, we
report the first case series in the literature of seven septuagenarians who
underwent RES in the form of anterior temporal lobectomy (ATL). The 10-year
median survival probability based on their comorbidities and age was more than
50%. Six patients had good surgical outcome (Engle I/II) with four of them being
completely free of disabling seizures after a median follow-up of almost 2years.
No significant medical or surgical morbidity was observed. However, three out of
the four patients undergoing pre- and post-RES neuropsychological testing showed
decline in memory function. Seizure-related injuries were noted in four out of
seven patients and may have been a motivation to proceed with RES in our cohort.
Our experience suggests that RES can be a safe and effective therapy in well
selected, septuagenarian patients with drug-resistant epilepsy.
Neuropsychological outcomes after RES in this population need further evaluation.
PMID- 28411523
TI - Doctors' experience of coordination across care levels and associated factors. A
cross-sectional study in public healthcare networks of six Latin American
countries.
AB - Improving coordination between primary care (PC) and secondary care (SC) has
become a policy priority in recent years for many Latin American public health
systems looking to reinforce a healthcare model based on PC. However, despite
being a longstanding concern, it has scarcely been analyzed in this region. This
paper analyses the level of clinical coordination between PC and SC experienced
by doctors and explores influencing factors in public healthcare networks of
Argentina, Brazil, Chile, Colombia, Mexico and Uruguay. A cross-sectional study
was carried out based on a survey of doctors working in the study networks (348
doctors per country). The COORDENA questionnaire was applied to measure their
experiences of clinical management and information coordination, and their
related factors. Descriptive analyses were conducted and a multivariate logistic
regression model was generated to assess the relationship between general
perception of care coordination and associated factors. With some differences
between countries, doctors generally reported limited care coordination, mainly
in the transfer of information and communication for the follow-up of patients
and access to SC for referred patients, especially in the case of PC doctors and,
to a lesser degree, inappropriate clinical referrals and disagreement over
treatments, in the case of SC doctors. Factors associated with a better general
perception of coordination were: being a SC doctor, considering that there is
enough time for coordination within consultation hours, job and salary
satisfaction, identifying the PC doctor as the coordinator of patient care across
levels, knowing the doctors of the other care level and trusting in their
clinical skills. These results provide evidence of problems in the implementation
of a primary care-based model that require changes in aspects of employment,
organization and interaction between doctors, all key factors for coordination.
PMID- 28411524
TI - The network structure of sex partner meeting places reported by HIV-infected MSM:
Opportunities for HIV targeted control.
AB - Baltimore, Maryland ranks among U.S. cities with the highest incidence of HIV
infection among men who have sex with men (MSM). HIV screening at sex partner
meeting places or venues frequented by MSM with new diagnoses and/or high HIV
viral load may reduce transmission by identifying and linking infected
individuals to care. We investigated venue-based clustering of newly diagnosed
MSM to identify high HIV transmission venues. HIV surveillance data from MSM
diagnosed between October 2012-June 2014 and reporting >=1 sex partner meeting
place were examined. Venue viral load was defined according to the geometric mean
viral load of the cluster of cases that reported the venue and classified as high
(>50,000 copies/mL), moderate (1500-50,000 copies/mL), and low (<1500 copies/mL).
143 MSM provided information on >=1 sex partner meeting place, accounting for 132
unique venues. Twenty-six venues were reported by > 1 MSM; of these, a tightly
connected cluster of six moderate viral load sex partner meeting places emerged,
representing 66% of reports. Small, dense networks of moderate to high viral load
venues may be important for targeted HIV control among MSM.
PMID- 28411525
TI - Health & access to care among working-age lower income adults in the Great
Recession: Disparities across race and ethnicity and geospatial factors.
AB - In the United States (US) and elsewhere, residents of low resource areas face
health-related disparities, and may experience different outcomes throughout
times of severe economic flux. We aimed to identify individual (e.g.
sociodemographic) and environmental (e.g. region, rurality) factors associated
with self-reported health and forgone medical care due to the cost of treatment
in the US across the Great Recession (2008-2009). We analyzed nationally
representative data (2004-2010) using the Behavioral Risk Factor Surveillance
System in the US. Individual and geospatial factors (rurality, census region)
were used to identify differences in self-reported health and forgone medical
care due to the cost. Adjusted-analyses taking into account individual and
geospatial factors among those with incomes <$50,000 identified multiple
differences across time, sex, education, disability, rurality and Census Region
for health. Similar analyses for forgone medical care found that those in the
Recovery and the Recession were more likely to report forgone care than before
the Recession. Having insurance and/or being employed (versus unemployed) was a
protective factor in terms of reporting fair/poor health and having to forgo
health care due to cost. Policies affecting improvements in health and access for
vulnerable populations (e.g., low-income minority adults) are critical.
Monitoring trends related to Social Determinants of Health, including the
relationship between health and place (e.g. Census region, rurality), is
necessary in efforts targeted towards ameliorating disparities.
PMID- 28411526
TI - Endovascular repair of a ruptured thoracic aortic dissection with a right sided
aortic arch: A case report.
AB - BACKGROUND: Emergency treatment of complex aortic pathology is challenging in the
setting of a right-sided aortic arch. We report the successful treatment of a
ruptured thoracic aortic aneurysm (TAA) in the setting of a Stanford type B
aortic dissection (TBAD) and right-sided aortic arch. PRESENTATION OF CASE: The
patient is a 66-year-old male with chronic kidney disease (CKD) admitted with
right sided chest pain and hypotension. Computed tomography angiography (CTA)
revealed a 5cm ruptured TAA in the setting of a TBAD and right-sided aortic arch.
The TBAD began just distal to the right common carotid artery and involved the
origin of the left subclavian artery (SCA). Using a totally percutaneous
approach, a conformable Gore(r) TAG(r) thoracic endoprosthesis was placed in
proximal descending thoracic aorta covering the left SCA. Aside from progression
of his pre-existing CKD, the patient had an uneventful recovery. CTA one-month
post-procedure revealed a type IB endoleak with degeneration of the distal
descending thoracic aorta. To exclude the endoleak, the repair was extended
distally using a Medtronic Valiant(r) thoracic stent graft. The left subclavian
artery was subsequently coil embolized to treat an additional retrograde
endoleak. The patient has done well with no further evidence of endoleak or
aneurysm expansion. CONCLUSION: Right-sided aortic arch presents challenges in
the emergency setting. CTA and post-processing reconstructions are very helpful.
While the endoleaks prompted additional interventions, the end result was
excellent. This case displays the importance of careful attention to detail and
follow-up in these complicated patients.
PMID- 28411527
TI - Development of sensitivity versus specificity for print in the visual word form
area.
AB - An area near the left lateral occipito-temporal sulcus that responds
preferentially to print has been designated as the visual word form area (VWFA).
Research suggests that specialization in this brain region increases as reading
expertise is achieved. Here we aimed to characterize that development in terms of
sensitivity (response to printed words relative to non-linguistic faces) versus
specificity (response to printed words versus line drawings of nameable objects)
in typically reading children ages 7-14 versus young adults as measured by
functional magnetic resonance imaging (fMRI). Relative to adults, children
displayed equivalent sensitivity but reduced specificity. These findings suggest
that sensitivity for print relative to non-linguistic stimuli develops relatively
early in the VWFA in the course of reading development, but that specificity for
printed words in VWFA is still developing through at least age 14.
PMID- 28411528
TI - Anodic oxidation of surfactants and organic compounds entrapped in micelles -
Selective degradation mechanisms and soil washing solution reuse.
AB - Formation of micelles at high surfactant concentration strongly modifies organic
pollutant oxidation mechanisms and kinetics during anodic oxidation (AO) using
boron doped diamond (BDD) anode. Results presented and discussed in this study
emphasized the following mechanisms: (i) micelles act as a protective environment
and reduce the availability of target molecules towards BDD(*OH); (ii) the use of
low current density strongly reduces micelle degradation kinetics due to both
steric hindrance phenomenon for oxidation of micelles at the BDD surface and
decrease of mediated oxidation in the bulk; (iii) compounds solubilized in
surfactant-containing solutions can be either oxidized after degradation of the
protective environment formed by micelles or if they are present as free extra
micellar compounds. Therefore, selective degradation of organic compounds
entrapped in micelles can be achieved by using low current density and high
surfactant concentration. In fact, these operating conditions strongly hinder
micelle oxidation, while free (extra-micellar) compounds can still be oxidized.
Then, the remaining entrapped compounds can also be continuously released in the
aqueous phase, according to the micellar/aqueous phase partitioning coefficient
(Km). These results have been applied for the treatment of a real polycyclic
aromatic hydrocarbon-containing soil washing (SW) solution. After 23 h of
treatment at 2.1 mA cm-2, 83% of phenanthrene, 90% of anthracene, 77% of pyrene
and 75% of fluoranthene were degraded and the treated SW solution was reused for
an additional SW step with only 5% lower extraction capacity than a fresh TW80
solution. A comparative study highlighted the superiority of this treatment
strategy, compared to the use of activated carbon for selective adsorption of
polycyclic aromatic hydrocarbons and SW solution reuse.
PMID- 28411529
TI - Free ammonia pre-treatment of secondary sludge significantly increases anaerobic
methane production.
AB - Energy recovery in the form of methane from sludge/wastewater is restricted by
the poor and slow biodegradability of secondary sludge. An innovative pre
treatment technology using free ammonia (FA, i.e. NH3) was proposed in this study
to increase anaerobic methane production. The solubilisation of secondary sludge
was significantly increased after FA pre-treatment at up to 680 mg NH3-N/L for 1
day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble
chemical oxygen demand; VS: volatile solids) was >10 times higher than that
without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential
assays showed that FA pre-treatment at above 250 mg NH3-N/L is effective in
improving anaerobic methane production. The highest improvement in biochemical
methane potential (B0) and hydrolysis rate (k) was achieved at FA concentrations
of 420-680 mg NH3-N/L, and was determined as approximately 22% (from 160 to 195 L
CH4/kg VS added) and 140% (from 0.22 to 0.53 d-1) compared to the secondary
sludge without pre-treatment. More analysis revealed that the FA induced
improvement in B0 and k could be attributed to the rapidly biodegradable
substances rather than the slowly biodegradable substances. Economic and
environmental analyses showed that the FA-based technology is economically
favourable and environmentally friendly. Since this FA technology aims to use the
wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to
enhance methane production from the WWTPs, it will set an example for the
paradigm shift of the WWTPs from 'linear economy' to 'circular economy'.
PMID- 28411530
TI - The influence of intrapartum opioid use on breastfeeding experience at 6 weeks
post partum: A secondary analysis.
AB - OBJECTIVE: To examine breastfeeding experiences up to 6 weeks postpartum for
mothers administered intranasal fentanyl, subcutaneous fentanyl or intramuscular
pethidine for intrapartum analgesia. DESIGN: A secondary analysis was undertaken
using the per-protocol dataset to examine the third phase of a larger randomised
controlled trial. This phase of the study examined breastfeeding intention and
experience from the first hour of birth to 6 weeks postpartum. Medical records
were audited and women were contacted at 6 weeks postpartum to complete a
telephone questionnaire. SETTING: Two maternity hospitals in South Australia.
PARTICIPANTS: Healthy women birthing at term received intranasal fentanyl (n=37),
subcutaneous fentanyl (n=37), or intramuscular pethidine (n=35). FINDINGS: While
maternal characteristics and birth outcomes were comparable between groups, women
who received either intranasal fentanyl or subcutaneous fentanyl experienced
fewer difficulties in establishing breastfeeding by 6 weeks postpartum when
compared to intramuscular pethidine (p<0.01). KEY CONCLUSIONS: Women who received
fentanyl reported that their neonates had less difficulties establishing
breastfeeding, compared to those who received pethidine. Therefore, for woman who
intend to breastfeed, fentanyl should be the preferred opiate, for the relief of
pain in labour. IMPLICATIONS FOR PRACTICE: When providing education to women in
relation to intrapartum pain relief it is important to consider the potential
influence on breastfeeding experience. This research provides evidence that
fentanyl is a suitable alternative to pethidine for women requesting parenteral
analgesia in labour.
PMID- 28411531
TI - Advanced oxidation of preservative agents in H2O2/UVC system - Kinetics study,
transformation products and toxicity assessment.
AB - Phenylphenol isomers (hydroxylated derivatives of biphenyl) are widely used as a
preservative agents and disinfectants in many branches of industry. This work
focuses on removal of phenylphenol isomers from aqueous solution using H2O2/UVC
process. The influence of different operating variables such as pH, initial
concentration of hydrogen peroxide, initial concentration of target compounds,
fluence rate and presence of radical scavengers on degradation rate was
investigated. Moreover, transformation products and toxicity of the reaction
solutions were studied. The reaction rate constants of hydroxyl radicals with
phenylphenol isomers were determined by using classical and competition kinetics.
The value of reaction rate constant depends on the position of the hydroxyl group
in the aromatic ring and follows the order: ortho- phenylphenol1, t-test p value < 0.05. The metabolic pathway analysis
was analyzed with MetaMapp and drew by CytoScape. Result shows that DON could
induce an increased protein synthesis to repair the damaged membrane protein
structure, in both kidney and spleen, with decrease of valine, leucine and
phenylalanine, et al. essential precursors for protein synthesis and energy
production; the energy metabolism in kidney disordered by DON, with the
decreasing of ribitol, glycerol 1-phosphate, et al. Furthermore, DON could lead
to the disorder in immunity function and nucleotide metabolism in spleen, with
decreasing trend of cytidine and alanine.
PMID- 28411544
TI - Coexposure to sulfamethoxazole and cadmium impairs development and attenuates
transcriptional response in sea urchin embryo.
AB - Among sulfonamides, sulfamethoxazole represents one of the most widely employed.
A considerable amount of sulfamethoxazole is introduced into the marine
environment after utilization in aquaculture. The cytotoxicity of
sulfamethoxazole relies mainly on arylhydroxylamine metabolites and it is
associated with the production of reactive oxygen species. Cadmium represents a
metal largely employed in several anthropic activities and it is toxic for all
living organisms even at low concentrations. Since it is not degraded, cadmium
irreversibly accumulates into cells. In order to understand the mechanisms of
response to changes in the chemical environment, we investigated by light
microscopy observations and RT-qPCR assays the impact of sulfamethoxazole and
cadmium in P. lividus sea urchin embryos. During development, embryos were
exposed to sulfamethoxazole amount comparable to that usually used in aquaculture
procedures and/or sublethal levels of cadmium chloride. Impairment of development
and biomarkers for inflammation, detoxification, metal scavenging and cell death
were inspected. Even though treatment with sulfamethoxazole apparently did not
affect development, it stimulated a remarkable molecular response to oxidative
stress. Moreover, combined exposure seriously compromised development and the
defense mechanisms to cadmium were blocked. This study leads to the conclusion
that coexposure to sulfamethoxazole and cadmium induces neutralizing effects on
sea urchin embryos. Thus, in marine areas nearby aquaculture farms, where
sulfamethoxazole discharge represents an important environmental contaminant,
cadmium occurrence may alter population dynamics of P. lividus.
PMID- 28411545
TI - A millimeter-scale observation of the competitive effect of phosphate on
promotion of arsenic mobilization in sediments.
AB - A millimeter-scale investigation is key to the understanding of the competitive
effects of phosphate(P) on arsenic(As) mobility in sediments by taking the great
biogeochemical heterogeneity of the sediments into consideration. In this study,
a microcosm experiment was performed in this aspect using high-resolution
dialysis and diffusive gradients in thin films (DGT) to simultaneously measure
dissolved and labile P, As, and iron (Fe) in sediments, respectively. With the
increase of P content in water from 0.02 mg L-1 to 0.20 and 2.4 mg L-1,
consistent release of As from sediments was observed. The concentrations of DGT
labile As increased significantly especially in the upper sediment layer (up to
12 times of the 0.02 mg P L-1 treatment) due to the competition of phosphate,
which corresponded well to the increase in DGT-labile P. There was limited
increase in dissolved P and As contents due to the buffering provided by sediment
solids, while the concentrations of both dissolved and DGT-labile Fe in sediments
decreased. A stoichiometric calculation showed that 47% and 8% of the added P
were removed through Fe(II) precipitation for the 0.20 and 2.4 mg P L-1
treatments, respectively, which greatly suppressed the release of As induced by P
competition for the 0.20 mg P L-1 treatment. The DGT-induced fluxes in sediments
(DIFS) modeling showed an increase in solid resupply to pore water As from
elevation of water P through the increases of the desorption rate constant from
5.4 to 31( * 10-7) s-1 and the sorption rate constant from 1.8 to 22( * 10-4) s
1.
PMID- 28411546
TI - Design and discovery of silybin analogues as antiproliferative compounds using a
ring disjunctive - Based, natural product lead optimization approach.
AB - The present study reports the synthesis and anticancer activity evaluation of
twelve novel silybin analogues designed using a ring disjunctive-based natural
product lead (RDNPL) optimization approach. All twelve compounds were tested
against a panel of cancer cells (i.e. breast, prostate, pancreatic, and ovarian)
and compared with normal cells. While all of the compounds had significantly
greater efficacy than silybin, derivative 15k was found to be highly potent (IC50
< 1 MUM) and selective against ovarian cancer cell lines, as well as other cancer
cell lines, compared to normal cells. Preliminary mechanistic studies indicated
that the antiproliferative efficacy of 15k was mediated by its induction of
apoptosis, loss of mitochondrial membrane potential and cell cycle arrest at the
sub-G1 phase. Furthermore, 15k inhibited cellular microtubules dynamic and
assembly by binding to tubulin and inhibiting its expression and function.
Overall, the results of the study establish 15k as a novel tubulin inhibitor with
significant activity against ovarian cancer cells.
PMID- 28411547
TI - Mechanical properties and state of miscibility in poly(racD,L-lactide-co
glycolide)/(L-lactide-co-epsilon-caprolactone) blends.
AB - Polymers based on lactic acid (PLA) are a very promising category of biopolymers.
As they are multi-stimuli responsive, can, in many ways, positively interact with
the host, stimulating the innate reparative machinery of the human body. Since
biopolymers for medical applications are subject to restrictive regulations,
blending stands out as an effective method for obtaining tailored properties
within a reduced time to market if compared to synthesis. Hence, in this study a
set of PDLGA/PLCL blends was obtained by means of thermoplastic techniques and
then further characterized. Evaluation techniques include GPC, NMR, DSC, tensile
testing and SEM. Although mixtures proved to be immiscible, a full range of
tensile properties was achieved. Observation of the surfaces of fracture provided
visual evidence of the deformation mechanisms that occurred during the tensile
tests which in the end led to failure. Interpretation of the thermal events based
on molecular characterization parameters revealed phase separation,
crystallization and plasticisation mechanisms that are relevant to any potential
applications based on mechanical performance and shape memory behaviour.
PMID- 28411548
TI - The production of injectable hydrazone crosslinked gellan gum-hyaluronan
hydrogels with tunable mechanical and physical properties.
AB - Gellan gum (GG) has been proposed for use in tissue engineering (TE) due to its
structural and functional similarities with alginate. The most traditional
crosslinking methods of GG, ionical and photocrosslinking, have downsides such as
loss of stability or phototoxicity, which can limit their use in certain
applications. In this study, an alternative hydrazone crosslinking method is
introduced. Hydrazone crosslinking is a simple method that produces no toxic
reagents or side-products. The method enables the fabrication of injectable
hydrogels. GG was combined with hyaluronan (HA) to improve some properties such
as cell attachment. The mechanical and physical properties of GG-HA hydrogels
were controlled by changing the molecular weight, the degree of modification, and
the ratio of polymer components. GG-HA hydrogels showed ionic nature of
deswelling in the presence of cations enabling the control of physical properties
in different solution environments. Due to the non-linear elastic behavior of
hydrogels and tissues, the stiffness as a function of strain was represented
instead of solely giving the second-order elastic constants. The stiffness of GG
HA hydrogels was similar to that of soft tissues at small strains.
PMID- 28411549
TI - Stability of knee ligament complex of Thiel-embalmed cadaver compared to in vivo
knee.
AB - BACKGROUND: The first biomechanical evaluation of new implants is usually carried
out with cadavers. Fixation of Thiel-embalmed cadavers is supposed to preserve
the histological structure, colour and consistency of the tissue and has a low
risk of infection and toxicity. However, the biomechanical properties of Thiel
fixated tissue are still unknown. The aim of this study was to quantify the
effect of the Thiel-embalming method on the elastic properties of the ligament
complex of the knee compared to in vivo knees during total knee arthroplasty.
METHODS: The results of biomechanical tensile tests with 10 Thiel-embalmed knees
were compared with the findings of 10 patients who underwent total knee
arthroplasty with a standardised knee balancer at our department. We
reconstructed the force-elongation curves of the medial and lateral ligament
complex and calculated the stiffness in direct correlation with overall soft
tissue stability in full extension and in 90 degrees of flexion. RESULTS: All
curves consisted of a non-linear part at the beginning and a linear part from
about 80N onwards. In full extension, median stiffness in the cadavers was
26.6N/mm for the medial compartment and 31.6N/mm for the lateral compartment. The
values for in vivo were 25.7N/mm for the medial compartment and 25.3N/mm for the
lateral compartment (p=0.684 for the medial compartment and p=0.247 for the
lateral compartment). In 90 degrees of flexion, median stiffness in the cadaver
group was 24.7N/mm for the medial compartment and 22.2N/mm for the lateral
compartment. In vivo, median stiffness was 30.3N/mm for the medial compartment
and 29.2N/mm for the lateral compartment (p=0.009 for the medial compartment and
p=0.143 for the lateral compartment). CONCLUSION: Stiffness of the medial and
lateral ligament complex in the knee was comparable between Thiel-embalmed
cadavers and in vivo patients during total knee arthroplasty. Thiel fixation
seems to preserve the soft tissue properties similar to those in vivo.
PMID- 28411550
TI - Nature based solutions to mitigate soil sealing in urban areas: Results from a 4
year study comparing permeable, porous, and impermeable pavements.
AB - Soil sealing is one of the most pervasive forms of soil degradation that follows
urbanization and, despite innovative pavements (i.e. pervious) are being
installed in urban areas to mitigate it, there is little research on the effects
of pervious pavements on soil water and carbon cycle and on the physiology of
urban trees. The aim of this 4-year experiment was to assess the effects of three
pavements, differing in permeability to water and gases, on some soil physical
parameters, and on growth and physiology of newly planted Celtis australis and
Fraxinus ornus. Treatments were: 1) impermeable pavement (asphalt on concrete sub
base); 2) permeable pavement (pavers on crushed rock sub-base); 3) porous design
(porous pavement on crushed rock sub-base); 4) control (unpaved soil, kept free
of weed by chemical control). Soil (temperature, moisture, oxygen content and CO2
efflux) and plant (above- and below-ground growth, leaf gas exchange, chlorophyll
fluorescence, water relations) parameters were measured. All types of pavements
altered the water cycle compared to unpaved soil plots, but this disturbance was
less intense in porous pavements than in other soil cover types. Porous pavements
allowed both higher infiltration and evaporation of water than both pavers and
asphalt. Reduction of evaporative cooling from soil paved with permeable and
impermeable pavements contributed to significant soil warming: at 20cm depth,
soils under concrete pavers and asphalt were 4 and 5 degrees C warmer than soil
covered by porous pavements and unpaved soils, respectively. Thus, enhancing
evaporation from paved soil by the use of porous pavements may contribute to
mitigating urban heat islands. CO2 greatly accumulated under impermeable and
permeable pavements, but not under porous pavements, which showed CO2 efflux
rates similar to control. Soil oxygen slightly decreased only beneath asphalt.
Growth of newly planted C. australis and F. ornus was little affected by pavement
type. Tree transpiration rapidly depleted soil moisture compared to the not
planted scenario, but soil moisture did not fall below wilting point
(particularly in the deeper soil layers, i.e. 40-50cm) in any treatment. While C.
australis showed similar leaf gas exchange and water relations in all treatments,
F. ornus showed a depression in CO2 assimilation and slight signs of stress of
the photosynthetic apparatus when planted in soil covered with impermeable
pavement. The effects of soil cover with different materials on tree growth and
physiology were little, because newly planted trees have most of their roots
still confined in the unpaved planting pit. Still, the reduction of soil sealing
around the planting pit triggered the establishment of sensitive species such as
ash. Further research is needed to assess the effects of different pavement types
on established, larger trees.
PMID- 28411551
TI - An alternative whole-body marker set to accurately and reliably quantify joint
kinematics during load carriage.
AB - Body armor covers anatomical landmarks that would otherwise be used to track
trunk and pelvis movement in motion analysis. This study developed and evaluated
a new marker set, and compared it to placing markers on the skin and over-top of
body armor. In our method, pelvis and trunk motions were measured using a custom
built sacral and upper-back marker cluster, respectively. Joint angles and ranges
of motion were determined while participants walked without and with body armor.
Angles were obtained from the new marker set and compared against conventional
marker sets placed on the skin or over-top the body armor. Bland-Altman analyses
compared the agreement of kinematic parameters between marker sets, while joint
angle waveforms were compared using inter-protocol coefficient of multiple
correlations (CMCs). The intra- and inter-session similarities of joint angle
waveforms from each marker set were also assessed using CMCs. There was a strong
agreement between joint angles from the new marker set and markers placed
directly on the skin at key anatomical landmarks. The agreement worsened with
markers placed on top of body armor. Inter-protocol CMCs comparing markers on
body armor to the new marker set were poor compared to CMCs between skin-mounted
markers and the new marker set. Intra- and inter-session repeatability were
higher for the new marker set compared to placing markers over-top of body armor.
The new marker set provides a viable alternative for researchers to reliably
measure trunk and pelvis motion when equipment, such as body armor, obscures
marker placement.
PMID- 28411552
TI - Reliability of four models for clinical gait analysis.
AB - Three-dimensional gait analysis (3DGA) has become a common clinical tool for
treatment planning in children with cerebral palsy (CP). Many clinical gait
laboratories use the conventional gait analysis model (e.g. Plug-in-Gait model),
which uses Direct Kinematics (DK) for joint kinematic calculations, whereas,
musculoskeletal models, mainly used for research, use Inverse Kinematics (IK).
Musculoskeletal IK models have the advantage of enabling additional analyses
which might improve the clinical decision-making in children with CP. Before any
new model can be used in a clinical setting, its reliability has to be evaluated
and compared to a commonly used clinical gait model (e.g. Plug-in-Gait model)
which was the purpose of this study. Two testers performed 3DGA in eleven CP and
seven typically developing participants on two occasions. Intra- and inter-tester
standard deviations (SD) and standard error of measurement (SEM) were used to
compare the reliability of two DK models (Plug-in-Gait and a six degrees-of
freedom model solved using Vicon software) and two IK models (two modifications
of 'gait2392' solved using OpenSim). All models showed good reliability (mean SEM
of 3.0 degrees over all analysed models and joint angles). Variations in joint
kinetics were less in typically developed than in CP participants. The modified
'gait2392' model which included all the joint rotations commonly reported in
clinical 3DGA, showed reasonable reliable joint kinematic and kinetic estimates,
and allows additional musculoskeletal analysis on surgically adjustable
parameters, e.g. muscle-tendon lengths, and, therefore, is a suitable model for
clinical gait analysis.
PMID- 28411553
TI - Cerium dioxide nanoparticles possess anti-inflammatory properties in the
conditions of the obesity-associated NAFLD in rats.
AB - BACKGROUND: Obesity is a risk factor for non-alcoholic fatty liver disease
(NAFLD). The disease is associated with impairment of pro/antioxidant equilibrium
and the inflammation in liver tissue. The aim of the work was to investigate the
anti-inflammatory properties of the nanocrystalline cerium dioxide (nCeO2) on the
rat model of NAFLD associated with monosodium glutamate (MSG)-induced obesity.
METHODS: The study was carried out on three groups of rats: control, MSG- and
MSG+nCeO2. They were injected with saline (control) or MSG. A month after born
MSG-rats had been treated with water in a volume of 2.9ml/kg, MSG+CeO2 groups -
with CeO2 intragastrically (i.g.). The anthropometric and carbohydrate metabolism
parameters, content of proinflammatory cytokines (interleukin (IL)-1beta, IL
12Bp40, interferon-gamma (INF-gamma)) and anti-inflammatory cytokines (IL-4, IL
10, tumor growth factor-beta (TGF-beta)) were measured by ELISA. RESULTS: We have
demonstrated the anti-obesity effect of nanocrystalline cerium dioxide and for
the first time its anti-inflammatory properties. Nanoparticles reduced the
content of pro-inflammatory cytokines (IL-1beta, IL-12Bp40) in rat serum and
restored the level of anti-inflammatory cytokines (IL-4, IL-10, TGF-beta) to the
control values. CONCLUSION: The precise mechanisms of this phenomenon remain to
be unclear but we suppose they are at least partially associated with the strong
anti-oxidant action of studied substance. Nanocrystalline cerium dioxide
attenuates the inflammatory processes in rat blood that can prevent obesity
complications and liver injury.
PMID- 28411554
TI - Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride
channels.
AB - Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum.
Recent studies demonstrated that emodin has anti-cancer activity in different
kinds of human cancer cell lines. However, the underlying mechanism has not been
very well studied. Our previous studies showed chloride channels is an important
target of anti-cancer drugs. Therefore, the purpose of this research was aimed to
explore the role of chloride channels involving in the anti-cancer activity of
emodin. The proliferation, cell cycle arrest and apoptosis of poorly
differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal
nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5
dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry.
The results indicated that emodin inhibited the CNE-2Z cell growth more
significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis
in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2
(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the
apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force
microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease
(AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel
blocker. These data could be a further evidence of chloride channel for
preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp
study also demonstrated that emodin can activate chloride channel in CNE-2Z cells
but not in NP69-SV40T cells. Furthermore, the activated chloride currents can
also be inhibited by chloride channel blockers indicating that chloride channel
may be the potential target molecular of emodin exerting its anti-tumor
efficiency in CNE-2Z cells.
PMID- 28411555
TI - Chemoproteomic profiling of targets of lipid-derived electrophiles by
bioorthogonal aminooxy probe.
AB - Redox imbalance in cells induces lipid peroxidation and generates a class of
highly reactive metabolites known as lipid-derived electrophiles (LDEs) that can
modify proteins and affects their functions. Identifying targets of LDEs is
critical to understand how such modifications are functionally implicated in
oxidative-stress associated diseases. Here we report a quantitative
chemoproteomic method to globally profile protein targets and sites modified by
LDEs. In this strategy, we designed and synthesized an alkyne-functionalized
aminooxy probe to react with LDE-modified proteins for imaging and proteomic
profiling. Using this probe, we successfully quantified >4000 proteins modified
by 4-hydroxy-2-nonenal (HNE) of high confidence in mammalian cell lysate and
combined with a tandem-orthogonal proteolysis activity-based protein profiling
(TOP-ABPP) strategy, we identified ~400 residue sites targeted by HNE including
reactive cysteines in peroxiredoxins, an important family of enzymes with anti
oxidant roles. Our method expands the toolbox to quantitatively profile protein
targets of endogenous electrophiles and the enlarged inventory of LDE-modified
proteins and sites will contribute to functional elucidation of cellular pathways
affected by oxidative stress.
PMID- 28411556
TI - Hydrogen peroxide modifies both activity and isoforms of acetylcholinesterase in
human neuroblastoma SH-SY5Y cells.
AB - The involvement of cholinergic system and the reactive oxygen species (ROS) in
the pathogenesis of some degenerative diseases has been widely reported; however,
the specific impact of hydrogen peroxide (H2O2) on the acetylcholinesterase
(AChE) activity as well as AChE isoform levels has not been clearly established.
Hence, the purpose of present study is to clarify whether H2O2 alters these
parameters. Human neuroblastoma SH-SY5Y cells were treated with H2O2 (1-1000uM)
for 24h and AChE activity and AChE and cytochrome c levels were evaluated. AChE
activity was strongly increased from 1uM to 1000uM of H2O2. The results of the
kinetic study showed that H2O2 affected Vmax but not Km; and also that H2O2
changed the sigmoid kinetic observed in control samples to hyperbolic kinetic.
Thus, results suggest that H2O2 acts as an allosteric activators. In addition,
H2O2, (100-1000uM) reduced the total AChE content and modified its isoform
profile (mainly 50-, 70-, and 132-kDa).H2O2 from 100uM to 1000uM induced
cytochrome c release confirming cell death by apoptosis. All these results
together suggest: a) the involvement of oxidative stress in the imbalance of
AChE; and b) treatment with antioxidant agents may be a suitable strategy to
protect cholinergic system alterations promoted by oxidative stress.
PMID- 28411557
TI - Controversy about pharmacological modulation of Nrf2 for cancer therapy.
AB - Conventional anticancer therapies such as radiotherapy and chemotherapies are
associated with oxidative stress generating reactive oxygen species (ROS) and
reactive aldehydes like 4-hydroxynonenal in cancer cells that govern them to die.
The main mechanism activated due to exposure of the cell to these reactive
species is the Nrf2-Keap1 pathway. Although Nrf2 was firstly perceived as a tumor
suppressor that inhibits tumor initiation and cancer metastasis, more recent data
reveal its role also as a pro-oncogenic factor. Discovery of the upregulation of
Nrf2 in different types of cancer supports such undesirable pathophysiological
roles of Nrf2. The upregulation of Nrf2 leads to activation of cytoprotective
genes thus helping malignant cells to withstand high levels of ROS and to avoid
apoptosis, eventually becoming resistant to conventional anticancer therapy.
Therefore, new treatment strategies are needed for eradication of cancer and in
this review, we will explore two opposing approaches for modulation of Nrf2 in
cancer treatments.
PMID- 28411559
TI - Synthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives.
AB - In the present study a series of 4-methyl-2-aryl-5-(2-aryl/benzyl thiazol-4-yl)
oxazole (4a-v) have been synthesized and evaluated for their preliminary
antitubercular, antimicrobial and cytotoxicity activity. Among all the
synthesized compounds, 4v reported comparable activity against dormant M.
tuberculosis H37Ra and M. bovis BCG strains with respect to standard drug
rifampicin. The active compounds from the antitubercular study were further
tested for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines
using MTT assay and showed no significant cytotoxic activity at the maximum
concentration evaluated. Further, the synthesized compounds were found to have
potential antibacterial activities with MIC range of 2.1-26.8 MUg/mL. High
potency, lower cytotoxicity and promising antimycobacterial activity suggested
that these compounds could serve as good leads for further optimisation and
development.
PMID- 28411558
TI - Sporadic periventricular nodular heterotopia: Classification, phenotype and
correlation with Filamin A mutations.
AB - OBJECTIVE: The purpose of this study was to better delineate the clinical
spectrum of periventricular nodular heterotopia (PNH) in a large patient
population after long term follow up. Specifically, this study aimed to relate
PNH subtypes to clinical or epileptic outcomes, epileptic discharges and
underlying Filamin A (FLNA) mutations by analyzing anatomical features. METHODS:
The study included 100 patients with radiologically confirmed nodular
heterotopia. Patients' FLNA gene sequences and medical records were analyzed. Two
sided Chi-square test and Fisher's exact t-test were used to assess associations
between the distribution of PNHs and specific clinical features. RESULTS: Based
on imaging data, patients were subdivided into three groups: (a) classical
(bilateral frontal and body, n=41 patients), (b) bilateral asymmetrical or
posterior (n=16) and (c) unilateral heterotopia (n=43). Most patients with
classical heterotopia were females (P=0.033) and were likely to have arachnoid
cysts (P=0.025) and cardiac abnormalities (P=0.041), but were mostly seizure
free. Additionally, hippocampal abnormalities (P=0.022), neurological deficits
(P=0.028) and cerebellar abnormalities (P=0.005) were more common in patients
with bilateral asymmetrical heterotopia. Patients with unilateral heterotopia
were prone to develop refractory epilepsy (P=0.041). FLNA mutations were
identified in 8 patients. CONCLUSIONS: Each group's distinctive genetic
mutations, epileptic discharge patterns and overall clinical outcomes confirm
that the proposed classification system is reliable. These findings could not
only be an indicator of a more severe morphological and clinical phenotype, but
could also have clinical implications with respect to the epilepsy management and
optimization of therapeutic options.
PMID- 28411561
TI - Selective attention moderates the relationship between attentional capture by
signals of nondrug reward and illicit drug use.
AB - BACKGROUND: The current study examined whether cognitive control moderates the
association between (non-drug) reward-modulated attentional capture and use of
alcohol and other drugs (AOD). METHODS: Participants were 66 university students
who completed an assessment including questions about AOD use, a visual search
task to measure value-modulated attentional capture, and a goal-directed
selective attention task as a measure of cognitive control. RESULTS: The
association between the effect of value-modulated attentional capture and illicit
drug use was moderated by level of cognitive control. Among participants with
lower levels of cognitive control, value-modulated attentional capture was
associated with illicit drug use. This was not the case among participants with
higher levels of cognitive control, who instead showed a significant association
between illicit drug use and self-reported impulsivity, as well as alcohol use.
CONCLUSIONS: These results provide support for models that view addictive
behaviours as resulting from interaction and competition between automatic and
more reflective processes. That is, the mechanisms that ultimately drive
addictive behaviour may differ between people low or high in cognitive control.
This has important implications for understanding the development and maintenance
of substance use disorders and potentially their treatment and prevention.
PMID- 28411562
TI - Comparing 3d and 2d computational modeling of an oil well blowout using MOHID
platform - A case study in the Campos Basin.
AB - The oil well blowout releases hydrocarbons into the marine environment as an oil
droplets and gas bubbles dispersion. The oil trajectory is strongly influenced by
physical, chemical and biological processes. In general, the ocean oil drift
studies are based on a two-dimensional approach, whereas the whole oil from a
well blowout can be represented by a surface oil leak in the same geographical
coordinates. This work is a case study, where MOHID software is used at the
Campos Basin region, in which the Lagrangian results of the surface oil leaks
were confronted to their well blowout scenarios in different conditions of depth,
seasonality (summer and winter), and use of dispersants at the source of the
leak. The research results reinforced the importance of the three-dimensional
approach to the scenario of deep and ultra-deep waters, especially for cases in
which the dispersant injection into the source of the leak was considered.
PMID- 28411560
TI - Comparison between the WHO and NIAAA criteria for binge drinking on drinking
features and alcohol-related aftermaths: Results from a cross-sectional study
among eight emergency wards in France.
AB - BACKGROUND: Binge drinking (BD) consists of heavy episodic alcohol use. Whereas
the World Health Organization (WHO) defines BD as 60g of alcohol or more per
occasion, the National Institute on Alcoholism and Alcohol Abuse (NIAAA)
conceives BD as drinking 70g (men) or 56g (women) in less than two hours. We
compared the subjects delineated by each definition. METHODS: Eight-center cross
sectional study among 11,695 subjects hospitalized in emergency wards.
Participants completed the Alcohol Use Disorders Identification Test -
Consumption (AUDIT-C), CAGE and Rapid Alcohol Problem Screen 4 (RAPS4-QF)
questionnaires. The WHO criteria were investigated using the RAPS4-QF.
Independent questions assessed the NIAAA criteria. The main medical admission
motive was noted. The characteristics of subjects meeting respectively: 1) the
exclusive WHO criteria (BD1); 2) the NIAAA criteria (BD2); and 3) no BD criteria
(noBD) were compared using multinomial regression analyses. Binary age- and
gender-adjusted regression analyses directly compared BD1 and BD2. Subjects with
at least four drinking occasions per week were excluded from the analyses, to
withdrawn regular heavy drinking. RESULTS: Compared to BD1, BD2 subjects were
more frequently males (OR=1.67 [1.39-2.0]), single (aOR=1.64 [1.36-1.98]) and
unemployed (aOR=1.57 [1.27-1.90]). BD2 reported significantly more drinks per
occasion, and higher heavy drinking frequencies. Previous alcohol-related remarks
from family (aOR=3.00 [2.53-3.56]), ever drinking on waking-up (aOR=2.05 [1.37
2.72]), and admission for psychiatric motive (aOR=2.27 [1.68-3.07]) were more
frequent among BD2 subjects. CONCLUSIONS: Compared to WHO criteria, NIAAA
criteria for BD delineate subjects with more concerning drinking patterns and
alcohol aftermaths.
PMID- 28411563
TI - Spatio-temporal trends in fire weather in the French Alps.
AB - The Alpine area is particularly sensitive to climatic and environmental changes
that might impact socio-ecosystems and modify the regime of natural hazards.
Among them, wildfire is of major importance as it threatens both ecosystems and
human lives and infrastructures. Wildfires result from complex interactions
between available vegetation fuels, climate and weather, and humans who decide of
the land use and are the main source of fire ignitions. The changes in fire
weather during the past decades are rather unknown in the French Alps especially
due to their complex topography. Moreover, local institutions and managers wonder
if the ongoing climate changes might increase fire risk and affect the
environmental quality and the different ecosystem services provided by the
mountain forests. In this context, we used the national forest fires database
together with daily meteorological observations from 1959 to 2015 to investigate
the changes in wildfire danger in the French Alps. We analysed the spatial and
temporal variations in terms of intensity, frequency, seasonality and window of
opportunity of two fire weather indices: the fine fuel moisture code (FFMC) and
the fire weather index (FWI) that measure the daily water content of vegetation
and the potential intensity of fires, respectively. Our results showed a major
contrast between Southern Alps with a high fire weather danger on average and a
significant increase in the past decades, and Northern Alps with low to moderate
danger on average that increased only at low elevations. This study contributes
to the understanding of the consequences of ongoings climate changes on wildfires
in the French Alps. It produced high resolution results that account for the
topographic and climatic variability of the area. Finally, the maps of the
different fire weather components have practical implications for fire management
and modelling and for preventing indirect effects of fires on ecosystems and
human assets.
PMID- 28411564
TI - Corrigendum to "Sea ice-associated decline in body condition leads to increased
concentrations of lipophilic pollutants in polar bears (Ursus maritimus) from
Svalbard, Norway" [Sci. Total Environ. 576 (2017) 409-419].
PMID- 28411565
TI - Enantioselective oxidative stress caused by chiral ionic liquids forms of 1-alkyl
3-methyl imidazolium tartrate on Scenedesmus obliquus.
AB - Ionic liquids (ILs) are widely used, but their potential threat to the
environment has recently gained more attention. The enantioselective oxidative
stress caused by chiral ionic liquids (CILs), such as 1-alkyl-3-methyl
imidazolium tartrate (RMIM T), on Scenedesmus obliquus was demonstrated in this
study. Stronger green fluorescence was observed in response to l-(+)-RMIM T
treatment than to d-(+)-RMIM T treatment, which suggested that more reactive
oxygen species (ROS) were stimulated by l-(+)-RMIM T. Significantly higher ROS
levels were recorded during the RMIM T treatments than in the control. There were
1.13-, 1.25-, 1.43-, 1.68-, and 1.96-fold increases over levels in the control in
the 3, 5, 10, 15, and 25mg/L d-(-)-HMIM T treatments, respectively, and 1.26-,
1.37-, 1.58-, 1.86- and 2.08-fold increases over levels in the control in the 3,
5, 10, 15, and 25mg/L l-(+)-HMIM T treatments, respectively. The total soluble
protein content decreased as the RMIM T concentration increased. The SOD and CAT
activities were stimulated at lower concentrations, but were inhibited at higher
concentrations. Regression analysis implied that ROS is the major factor
responsible for the oxidative damage caused by RMIM T. The ultrastructural
morphology analysis showed that plasmolysis and damage to the chloroplasts,
starch granule decreases, and lipid granule increased, and pyrenoid and nucleoid
damage had occurred. These results showed that enantioselective oxidative stress
and oxidative damage were caused by d-(+)-RMIM T and l-(+)-RMIM T, and that l-(+)
RMIM T caused more damage than d-(+)-RMIM T.
PMID- 28411566
TI - Ambient fine particulate matter (PM2.5) in Canadian oil sands communities:
Levels, sources and potential human health risk.
AB - An investigation of levels and potential sources affecting ambient fine
particulate matter (PM2.5) and associated risk to public health was undertaken at
two Canadian oil sands communities (Fort McKay and Fort McMurray) using a 4-year
dataset (2010-2013). Geometric mean concentrations of PM2.5 at Fort McKay and
Fort McMurray are not considered high and were 5.47MUg/m3 (interquartile range,
IQR=3.02-8.55MUg/m3) and 4.96MUg/m3 (IQR=3.20-7.04MUg/m3), respectively.
Carcinogenic risks of trace elements were below acceptable (1*10-6) and/or within
tolerable risk (1*10-4), and non-carcinogenic risks were below a safe level of
concern (hazard index=1). Positive matrix factorization (PMF) modeling revealed
five sources, where fugitive dust appeared as the major contributor to PM2.5 mass
(Fort McKay: 32%, Fort McMurray: 46%) followed by secondary sulfate (31%, 42%)
and secondary nitrate/biomass burning (26%, 8%). Other minor sources included a
mining/mobile and a Mn-rich/Mn-Co-Zn-rich source. Source-specific risk values
were also estimated and were well below acceptable and safe level of risks.
Further work would be needed to better understand the contribution of secondary
organic aerosols to PM2.5 formation in these oil sands communities.
PMID- 28411567
TI - Comment on "Environmental exposure to manganese in air: Associations with tremor
and motor function" by Bowler et al. (2016).
PMID- 28411568
TI - Projecting biodiversity and wood production in future forest landscapes: 15 key
modeling considerations.
AB - A variety of modeling approaches can be used to project the future development of
forest systems, and help to assess the implications of different management
alternatives for biodiversity and ecosystem services. This diversity of
approaches does however present both an opportunity and an obstacle for those
trying to decide which modeling technique to apply, and interpreting the
management implications of model output. Furthermore, the breadth of issues
relevant to addressing key questions related to forest ecology, conservation
biology, silviculture, economics, requires insights stemming from a number of
distinct scientific disciplines. As forest planners, conservation ecologists,
ecological economists and silviculturalists, experienced with modeling trade-offs
and synergies between biodiversity and wood biomass production, we identified
fifteen key considerations relevant to assessing the pros and cons of alternative
modeling approaches. Specifically we identified key considerations linked to
study question formulation, modeling forest dynamics, forest processes, study
landscapes, spatial and temporal aspects, and the key response metrics -
biodiversity and wood biomass production, as well as dealing with trade-offs and
uncertainties. We also provide illustrative examples from the modeling literature
stemming from the key considerations assessed. We use our findings to reiterate
the need for explicitly addressing and conveying the limitations and
uncertainties of any modeling approach taken, and the need for interdisciplinary
research efforts when addressing the conservation of biodiversity and sustainable
use of environmental resources.
PMID- 28411569
TI - Melamine-formaldehyde derived porous carbons for adsorption of CO2 capture.
AB - In this work, we report carbon adsorbents obtained from high nitrogen content
melamine-formaldehyde resin as starting material and mesoporous zeolite MCM-41 as
template through nanocasting technique. To synthesize different carbon structure
adsorbents with improved textural and surface properties, the material undergo
carbonization followed by physical activation under CO2 atmosphere at different
temperatures. Characterizations of the adsorbents using SEM, TEM, XPS, nitrogen
sorption, CHN, TKN, and TPD have been carried out. Characterization results
reveal the development of nanostructured carbon adsorbents with better texture
and surface properties as compared to the sample prepared by direct
carbonization. Sample prepared at carbonization-activation temperature of 700
degrees C shows highest basicity, surface area (193.28 m2 g-1) and pore volume
(0.32 cm3 g-1). Performance evaluation of adsorbent was performed thermo
gravimetrically at different temperatures and concentrations and was found that
the adsorbent synthesized at 700 degrees C exhibit highest CO2 uptake of 0.93
mmol g-1 with nitrogen content of 22.73%. It was found that both surface area and
nitrogen functional group have a major impact on adsorption capacity.
Physiosorption process was confirmed by a decrease in adsorption capacity with
increase in temperature. Three kinetic models and isotherms were used in this
study and found that fractional order kinetic model and Freundlich isotherm best
fitted with the experimental data. Isotherm study depicts the heterogeneous
nature of adsorbent surface. Adsorbent exhibited complete regenerability and was
stable over four adsorption-desorption cycles. Low value of isosteric heat of
adsorption of 15.75 kJ mol-1, indicates physiosorption process. Negative value of
DeltaG0 and DeltaH0 confirms spontaneous, feasible and exothermic nature of
adsorption process.
PMID- 28411570
TI - Impacts of coal fly ash on plant growth and accumulation of essential nutrients
and trace elements by alfalfa (Medicago sativa) grown in a loessial soil.
AB - Coal fly ash (CFA) is a problematic solid waste all over the world. One distinct
beneficial reuse of CFA is its utilization in land application as a soil
amendment. A pot experiment was carried out to assess the feasibility of using
CFA to improve plant growth and increase the supply of plant-essential elements
and selenium (Se) of a loessial soil for agricultural purpose. Plants of alfalfa
(Medicago sativa) were grown in a loessial soil amended with different rates (5%,
10%, 20% and 40%) of CFA for two years and subjected to four successive cuttings.
Dry mass of shoots and roots, concentrations of plant-essential elements and Se
in plants were measured. Shoot dry mass and root dry mass were always
significantly increased by 5%, 10% and 20% CFA treatments, and by 40% CFA
treatment in all harvests except the first one. The CFA had a higher supply of
exchangeable phosphorus (P), magnesium (Mg), copper (Cu), zinc (Zn), molybdenum
(Mo), and Se than the loessial soil. Shoot P, calcium (Ca), Mg, Mo, boron (B),
and Se concentrations were generally markedly increased, but shoot potassium (K),
Cu, and Zn concentrations were generally reduced. The CFA can be a promising
source of some essential elements and Se for plants grown in the loessial soil,
and an application rate of not higher than 5% should be safe for agricultural
purpose without causing plant toxicity symptoms in the studied loessial soil and
similar soils. Field trials will be carried out to confirm the results of the pot
experiment.
PMID- 28411571
TI - A Structural Equation Modeling approach to water quality perceptions.
AB - Researches on water quality perceptions have used various techniques and models
to explain relationships between specific variables. Surprisingly, Structural
Equation Modeling (SEM) has received little attention in water quality
perceptions studies, and reporting has been inconsistent among existing studies.
One objective of this article is to provide readers with a methodological example
for conducting and reporting SEM. Another objective is to build a model that
explains the different relationships among the diverse factors highlighted by
previous studies on water quality perceptions. Our study focuses on the factors
influencing people's perceptions of water quality in the Appalachian region. As
such, researchers have conducted a survey in a mid-sized city in northcentral
West Virginia to assess residents' perceptions of water quality for drinking and
recreational purposes. Specifically, we aimed to understand the relationships
between perceived water quality, health risk perceptions, organoleptic
perceptions, environmental concern, area satisfaction and perceptions of surface
water quality. Our model provided a good fit that explained about 50% of the
variance in health risk perceptions and 43% of the variance in organoleptic
perceptions. Environmental concern, area satisfaction and perceived surface water
quality are important factors in explaining these variances. Perceived water
quality was dismissed in our analysis due to multicollinearity. Our study
demonstrates that risk communication needs to be better addressed by local
decision-makers and water managers.
PMID- 28411572
TI - Adaptive response of arbuscular mycorrhizal symbiosis to accumulation of elements
and translocation in Phragmites australis affected by cadmium stress.
AB - Arbuscular mycorrhizal (AM) fungi have been reported to play a central role in
improving plant tolerance to cadmium (Cd)-contaminated sites. This is achieved by
enhancing both the growth of host plants and the nutritive elements in plants.
This study assessed potential regulatory effects of AM symbiosis with regard to
nutrient uptake and transport, and revealed different response strategies to
various Cd concentrations. Phragmites australis was inoculated with Rhizophagus
irregularis in the greenhouse cultivation system, where it was treated with 0-20
mg L-1 of Cd for 21days to investigate growth parameters, as well as Cd and
nutritive element distribution in response to AM fungus inoculation. Mycorrhizal
plants showed a higher tolerance, particularly under high Cd-level stress in the
substrate. Moreover, our results determined the roots as dominant Cd reservoirs
in plants. The AM fungus improved Cd accumulation and saturated concentration in
the roots, thus inhibiting Cd uptake to shoots. The observed distributions of
nutritive elements and the interactions among these indicated the highest
microelement contribution to roots, Ca contributed maximally in leaves, and K and
P contributed similarly under Cd stress. In addition, AM fungus inoculation
effectively impacted Mn and P uptake and accumulation while coping with Cd
toxicity. This study also demonstrated translocation factor from metal
concentration (TF) could be a good parameter to evaluate different transportation
strategies induced by various Cd stresses in contrast to the bioconcentration
factor (BCF) and translocation factor from metal accumulation (TF').
PMID- 28411573
TI - Frequency of non-right-handedness in bipolar disorder and schizophrenia.
AB - Increased non-right-handedness (NRH) probably reflects neurodevelopmental
abnormalities in psychiatric disorders. Past studies of NRH have focused more on
schizophrenia (SZ) than bipolar disorder (BPD). We report results on NRH in two
large studies. In (1), NRH was compared among BPD patients with psychosis, SZ
patients, and healthy controls (HC). NRH was elevated in BPD with psychosis and
SZ patients relative to HC, but not SZ relative to BPD. In (2), NRH was compared
between BPD patients with and without psychosis. NRH was similarly elevated in
both. The findings suggest that NRH may reflect shared brain anomalies in SZ and
BPD.
PMID- 28411574
TI - Risperidone versus olanzapine in the acute treatment of Persistent Delusional
Disorder: A retrospective analysis.
AB - There is a dearth of prospective trials studying treatment response in Persistent
Delusional Disorder (PDD) to guide clinical practice. Available retrospective
data indicate good response to second-generation antipsychotics (SGAs). We
selected the data of patients prescribed either olanzapine or risperidone from a
retrospective chart review of PDD (n=455) at our centre. We compared the two
groups olanzapine (n =86) versus risperidone (n =280) on dose, drug adherence,
response and adverse effects. The two groups were comparable on socio-demographic
and clinical characteristics of PDD. There was no statistically significant
difference between the two groups on adherence (>80%) and response to treatment
(>52% good response). Olanzapine was effective at lower mean chlorpromazine
equivalents than risperidone. Logistic regression analysis identified shorter
mean duration of illness, good adherence and absence of substance dependence as
predictors of good response to both drugs. Our study indicates that acute PDD
responds well to treatment with both risperidone and olanzapine, provided
adherence can be ensured. In the absence of specific treatment guidelines and
randomized controlled trials for PDD, our analysis reaffirms the efficacy of
SGAs.
PMID- 28411575
TI - The risk factors of possible PTSD in individuals exposed to a suicide attack in
Turkey.
AB - The aims of this study were to determine both the rate of possible PTSD in
individuals who were exposed to a suicide attack in Ankara, Turkey, and the
factors that relate to the elevated risk for PTSD in individuals who survived
that suicide attack. The researchers carried out the study with 93 participants
who had attended a meeting held in Ankara on October 10, 2015. Participants
completed a sociodemographic information form, the Traumatic Stress Symptom
Checklist (TSSC), the Post-Traumatic Cognitions Inventory, the Beck Depression
Inventory (BDI), and the Influence of Perceived Societal Attitudes Questionnaire
(IPSAQ). Twenty-three of participants were determined to have possible PTSD
(24.7%). Participants who were exposed previously to a suicide attack, who
witnessed a life-threatening injury, who had the need for psychological help, and
who had suicidal thoughts had significantly higher rates of possible PTSD. The
IPSAQ, BDI, and TSSC scores were significantly higher in the participants with
possible PTSD. The IPSAQ score was found to be related to the development of
possible PTSD. This study demonstrated that in participants who had been exposed
to a terrorist attack, the negative impact of perceived societal attitudes toward
the victims was related to the possible development of PTSD.
PMID- 28411576
TI - A population-based study of premorbid scholastic achievement among patients with
psychiatric disorders.
AB - Population-based studies of premorbid cognitive functioning in schizophrenia have
found verbal deficits and low IQ scores. It remains unclear, however, whether
premorbid deficits are specific to schizophrenia, compared with other psychiatric
disorders. Moreover, studies using school-based measures are few and their
results inconsistent. This study assesses the eighth-grade (ages 13-14; n=11,
418) scholastic performance of adults with psychiatric disorders (n=194, 1.7,
particularly with schizophrenia (n=86, 0.8%), comparing the results with those of
their normative peers. The researchers examined report cards of eighth-graders at
state secular schools in Jerusalem over a ten-year period (1978-1988), applying
ANOVA and logistic regression models to evaluate associations between school
performance and subsequent psychiatric hospitalization. The findings indicated
that participants hospitalized with varied psychiatric disorders had lower grades
in mathematics, gym, handcraft and academic core subjects, with significantly
lower overall scores. Amended logistic regression models indicate that reduced
performance (in mathematics, gym, handcraft and overall scores) was correlated
with an increasing likelihood of hospitalization for the psychiatric disorders
group and the subgroup with schizophrenia-related ailments. These results imply
that eighth-grade school performance in core subjects is poorer among persons
later hospitalized with psychiatric disorders than that of their classmates.
PMID- 28411577
TI - Perceived parental child rearing and attachment as predictors of anxiety and
depressive disorder symptoms in children: The mediational role of attachment.
AB - The present study aimed to examine (a) the relative contribution of perceived
parental child-rearing behaviors and attachment on anxiety and depressive
symptoms, and (b) the role of attachment as a possible mediator of the
association between parental rearing and anxiety and depression. A sample of 1002
children (aged 9-12 years) completed a booklet of self-report questionnaires
measuring parental rearing behaviors, attachment towards peers, and DSM anxiety
and depressive disorder symptoms. We found that parental aversiveness, parental
neglect, and fearful/preoccupied attachment, each accounted for a significant
amount of the variance in both anxiety and depressive symptoms. In addition,
parental overcontrol was found to account for unique variance in anxiety whereas
communication/warmth accounted for a significant proportion of the variance in
depression. A relevant finding was that fearful/preoccupied attachment was found
to mediate the association between parental rearing behaviors and both anxiety
and depression. Parental rearing behaviors and attachment to peers may act as
risk factors to the development and/or maintenance of anxiety and depressive
symptomatology in children. Findings may contribute to outline preventive and/or
treatment programs to prevent or reduce both clinical anxiety and depression
during childhood.
PMID- 28411578
TI - Differential effects of low-dose fludarabine or 5-fluorouracil on the tumor
growth and myeloid derived immunosuppression status of tumor-bearing mice.
AB - Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and
play a key role in the suppression of the innate and adaptive immunity.
Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in
different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to
reduce the tumor size by depleting MDSCs. Here, we asked whether the purine
analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma
model, we demonstrated that in mice with advanced tumors (where MDSC-induced
suppression was present), treatment with a single low-dose Flu (25, 50, 100mg/kg)
elevated the numbers of splenic MDSCs and serum arginase activity, and
simultaneously, increased the tumor growth (only the highest dose). On the other
hand, in mice with palpable tumors (where the MDSC-induced suppression was in
progress), treatment with Flu had no significant effects on the tumor growth or
the number of splenic MDSCs. In contrast to Flu, treatment with low-dose 5-FU,
irrespective of tumor stage, caused tumor regression which coincided with
significant reductions in the numbers of splenic MDSCs and blood neutrophils, but
increases in the ratios of splenic CD4+ T and CD8+ T cells to suppressive MDSCs.
Finally, in healthy mice (where MDSC-induced immuosuppression did not exist), 5
FU, but not Flu induced significant decreases in the number of myeloid cells in
the bone marrow, naturally occurring splenic MDSCs and thymocytes. In conclusion,
Flu exacerbates MDSC-induced immunosuppression in a tumor stage-dependent manner,
whereas 5-FU alleviates the suppressive effects of MDSC at all stages of tumor
development.
PMID- 28411579
TI - Self-injury and aggression in adults with tuberous sclerosis complex: Frequency,
associated person characteristics, and implications for assessment.
AB - : Even though self-injury and aggression are common in tuberous sclerosis complex
(TSC), understanding of these behaviours in adults with TSC and intellectual
disability (ID) is limited. Little is known about their frequency in comparison
to other ID-related genetic disorders or their association with other TSC
Associated Neuropsychiatric Disorders (TAND). This study determined the caregiver
reported frequency of self-injury and aggression in adults with TSC plus ID in
comparison to Down syndrome (DS) and Angelman syndrome (AS), and assessed
demographic and behavioural characteristics associated with the occurrence of
each behaviour in TSC. Rates of self-injury and aggression in adults with TSC
plus ID were 31% and 37.9% respectively. The odds of self-injury for adults with
TSC were nearly twice as high as the odds for adults with DS, and the odds of
aggression were over 2.5 times higher for adults with TSC than for adults with
DS. When compared to adults with AS, odds of self-injury in TSC were around half
those of the AS group, and odds of aggression were less than a third of those for
adults with AS. These differences were not statistically significant. In adults
with TSC, poorer communication and socialisation skills, gastric health problems
and impulsivity were associated with self-injury; compulsive behaviour and
impulsivity were associated with aggression. Caregivers and professionals should
be alert to the likelihood of these behaviours in adults with TSC plus ID, and to
characteristics associated with increased risk for their occurrence. We suggest
assessment strategies to identify those at elevated risk. WHAT THIS PAPER ADDS:
This paper adds specific examination of behavioural difficulties in adults with
tuberous sclerosis complex who also have intellectual disability, a population at
heightened risk of adverse behavioural outcomes which has received limited
focussed examination to date. Findings support existing suggestions that there is
relatively high risk for both self-injury and aggression, and provide novel
insight into characteristics that may be associated with the presence of these
behaviours.
PMID- 28411580
TI - Comparative analysis of the liver transcriptome of Pelteobagrus vachellii with an
alternative feeding time.
AB - Pelteobagrus vachellii, an important freshwater fish in China, shows
predominantly nocturnal behavior. To better understand the growth and molecular
mechanisms underlying altered feeding times in this species, we studied the
growth and liver transcriptome of P. vachellii with shifted feeding times. In
this study, a 9-week growth trial was conducted on male P. vachellii (mean
weight+/-S.E.=1.05+/-0.36g) with commercial feed. Two triplicate groups of fish
were fed either at 0800 (day group, control) or at 2000 (night group) with the
same amount of feed. After nine weeks, a significant increase in growth was
observed in the night group, demonstrated by the specific growth rate (SGR).
Using high-throughput RNA-seq, 70,793,844 and 67,930,610 paired-end clean reads
were obtained from six cDNA libraries of P. vachellii liver, and 60,069 unigenes
were assembled. Gene expression comparison revealed that 122 genes were
significantly up-regulated and 59 genes were significantly down-regulated in the
night group. Gene pathway and GO enrichment analyses revealed metabolic responses
of genes and gene networks related to protein, lipid and carbohydrate metabolism
and rhythms. This study indicates that an alternative feeding time can improve
growth and create metabolic alterations in the liver of P. vachellii.
PMID- 28411581
TI - Silica nanoparticles and lead acetate co-exposure triggered synergistic
cytotoxicity in A549 cells through potentiation of mitochondria-dependent
apoptosis induction.
AB - The adverse effects of PM2.5 are the results of combined toxicities of finer
particles and their adsorbed toxic pollutants. Nevertheless, the combined
toxicity of finer particles and air pollutants still remains unclear. The present
study was therefore undertaken to investigate the combined cytotoxicity of silica
nanoparticles (nano-SiO2, a typical atmospheric ultrafine particle) and lead
acetate (Pb, a representative air pollutant) in A549 cells focusing on
mitochondria-dependent apoptosis induction. The results showed that Pb exposure
alone induced mitochondria-dependent apoptosis in A549 cells, as evidenced by
increased apoptotic rate and Bax/Bcl-2 ratio, up-regulated caspases 3 and 9
expressions as well as decreased mitochondrial membrane potential. Non-cytotoxic
concentration of nano-SiO2 exposure alone did not trigger apoptosis in A549
cells, but potentialized the apoptotic changes when co-exposure with Pb.
Factorial analyses revealed synergistic interactions were responsible for the
potentiation of joint apoptotic responses.
PMID- 28411582
TI - Dexmedetomidine attenuates propofol-induce neuroapoptosis partly via the
activation of the PI3k/Akt/GSK3beta pathway in the hippocampus of neonatal rats.
AB - Recent studies have demonstrated that propofol causes neurodegeneration in
developing brains. Evidence has shown that dexmedetomidine has neuroprotective
effects. However, whether dexmedetomidine can reduce propofol-induced
neuroapoptosis and by what mechanisms it acts remain unclear. We investigated
whether dexmedetomidine can attenuate propofol-induced neuroapoptosis by
disturbing the PI3K/Akt/GSK3beta pathway during brain development. Seven-day-old
rats were randomly exposed to 100mg/kg propofol and 100mg/kg propofol plus
different doses of dexmedetomidine or 100mg/kg propofol and 75MUg/kg
dexmedetomidine plus PI3K inhibitor LY294002 or GSK3beta inhibitor TDZD-8. TEM
and TUNEL were used to detect neuronal structure changes and apoptosis. The
expression of phospho-Akt, phospho-GSK3beta, Akt and GSK3beta were quantified
using western blots and immunofluorescence. Pretreatment with different doses of
dexmedetomidine protected against propofol-induced neuroapoptosis. Furthermore,
propofol decreased the levels of phospho-Akt and phospho-GSK3beta, whereas
dexmedetomidine partially reversed this inhibition. In addition, treatment with
LY294002 inhibited the neuroprotection of dexmedetomidine, whereas TDZD-8
enhanced neuroprotection. Our results indicate that dexmedetomidine prevents
propofol-induced neuroapoptosis by increasing the levels of phospho-Akt and
phospho-GSK3beta.
PMID- 28411583
TI - How plants cope with UV-B: from perception to response.
AB - Ultraviolet-B radiation (UV-B) is an intrinsic part of the solar radiation that
reaches the Earth's surface and affects the biosphere. Plants have evolved a
specific UV-B signaling pathway mediated by the UVR8 photoreceptor that regulates
growth, development, and acclimation. Major recent advances have contributed to
our understanding of the UVR8 photocycle, UV-B-responsive protein-protein
interactions, regulation of UVR8 subcellular localization, and UVR8-regulated
physiological responses. Here, we review the latest progress in our understanding
of UVR8 signaling and UV-B responses, which includes studies in the unicellular
alga Chlamydomonas reinhardtii and the flowering plant Arabidopsis.
PMID- 28411584
TI - Illuminating colors: regulation of carotenoid biosynthesis and accumulation by
light.
AB - Light stimulates the biosynthesis of carotenoids and regulates the development of
plastid structures to accommodate these photoprotective pigments. Work with
Arabidopsis revealed molecular factors coordinating carotenoid biosynthesis and
storage with photosynthetic development during deetiolation, when underground
seedlings emerge to the light. Some of these factors also adjust carotenoid
biosynthesis in response to plant proximity (i.e., shade), a mechanism that was
readapted in tomato to monitor fruit ripening progression. While light positively
impacts carotenoid production and accumulation in most cases, total carotenoid
levels decrease in roots of colored carrot cultivars when illuminated. The recent
discovery that such cultivars might be photomorphogenic mutants provides an
explanation for this striking phenotype.
PMID- 28411585
TI - The association between air pollution and type 2 diabetes in a large cross
sectional study in Leicester: The CHAMPIONS Study.
AB - BACKGROUND: Observational evidence suggests there is an association between air
pollution and type 2 diabetes; however, there is high risk of bias. OBJECTIVE: To
investigate the association between air pollution and type 2 diabetes, while
reducing bias due to exposure assessment, outcome assessment, and confounder
assessment. METHODS: Data were collected from 10,443 participants in three
diabetes screening studies in Leicestershire, UK. Exposure assessment included
standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter
concentrations in a 1*1km area at the participant's home postcode. Three-year
exposure was investigated in the primary analysis and one-year exposure in a
sensitivity analysis. Outcome assessment included the oral glucose tolerance test
for type 2 diabetes. Confounder assessment included demographic factors (age,
sex, ethnicity, smoking, area social deprivation, urban or rural location),
lifestyle factors (body mass index and physical activity), and neighbourhood
green space. RESULTS: Nitrogen dioxide and particulate matter concentrations were
associated with type 2 diabetes in unadjusted models. There was no statistically
significant association between nitrogen dioxide concentration and type 2
diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91,
1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further
adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further
adjustment for neighbourhood green space. The associations between particulate
matter concentrations and type 2 diabetes were also explained away by demographic
factors. There was no evidence of exposure definition bias. CONCLUSIONS:
Demographic factors seemed to explain the association between air pollution and
type 2 diabetes in this cross-sectional study. High-quality longitudinal studies
are needed to improve our understanding of the association.
PMID- 28411586
TI - Inherited and Acquired Muscle Weakness: A Moving Target for Diagnostic Muscle
Biopsy.
AB - Inherited and acquired muscular weakness is caused by multiple conditions. While
the inherited ones are mostly caused by mutations in genes coding for myopathic
or neurogenic diseases, the acquired ones occur due to inflammatory, endocrine,
or toxic etiologies. Precise diagnosis of a specific disease may be challenging
and may require a multidisciplinary approach. What is the current place for a
diagnostic biopsy of skeletal muscle? Diagnostic muscle biopsy lost in this
context its first-tier place in the primary diagnostic workup for some diseases,
but it is still mandatory for others. We here summarize conditions in which we
believe a diagnostic sample is most relevant and mention those in which a biopsy
may be secondary or can even be left out. We would like to stress that muscle
biopsy nowadays has a new important place in description and definition of new
diseases, for example, discovered by modern genetic approaches.
PMID- 28411587
TI - Novel STAC3 Mutations in the First Non-Amerindian Patient with Native American
Myopathy.
AB - Native American myopathy (NAM) is an autosomal recessive congenital myopathy, up
till now exclusively described in Lumbee Indians who harbor one single homozygous
mutation (c.1046G>C, pW284S) in the STAC3 gene, encoding a protein important for
proper excitation-contraction coupling in muscle. Here, we report the first non
Amerindian patient of Turkish ancestry, being compound heterozygous for the
mutations c.862A>T (p.K288*) and c.432+4A>T (aberrant splicing with skipping of
exon 4). Symptoms in NAM include congenital muscle weakness and contractures,
progressive scoliosis, early ventilatory failure, a peculiar facial gestalt with
mild ptosis and downturned corners of the mouth, short stature, and marked
susceptibility to malignant hyperthermia. This case shows that NAM should also be
considered in non-Indian patients with congenital myopathy, and suggests that
STAC3 mutations should be taken into account as a potential cause of malignant
hyperthermia.
PMID- 28411588
TI - Dynamics in higher lying excited states: Valence to Rydberg transitions in the
relaxation paths of pyrrole and methylated derivatives.
AB - The involvement of intermediate Rydberg states in the relaxation dynamics of
small organic molecules which, after excitation to the valence manifold, also
return to the valence manifold is rarely observed. We report here that such a
transiently populated Rydberg state may offer the possibility to modify the
outcome of a photochemical reaction. In a time resolved photoelectron study on
pyrrole and its methylated derivatives, N-methyl pyrrole and 2,5-dimethyl
pyrrole, 6.2 eV photons (200 nm) are used to excite these molecules into a bright
pipi* state. In each case, a pi3p-Rydberg state, either the B1(pi3py) or the
A2(pi3pz) state, is populated within 20-50 fs after excitation. The wavepacket
then proceeds to the lower lying A2(pisigma*) state within a further 20 fs, at
which point two competing reaction channels can be accessed: prompt N-H (N-CH3)
bond cleavage or return to the ground state via a conical intersection accessed
after ring puckering, the latter of which is predicted to require an additional
100-160 fs depending on the molecule.
PMID- 28411589
TI - Excited states from modified coupled cluster methods: Are they any better than
EOM CCSD?
AB - Simplifications or modifications of coupled cluster methods such as the CCSD
(coupled cluster singles and doubles) model often perform better than the
original method in providing the total energy, equilibrium geometries, and
harmonic vibration frequencies for the ground state. Three such methods that have
been recently proposed include 2CC, parameterized CCSD generalizations, and
distinguishable cluster singles and doubles (DCSD) approach. In this paper, we
lay the theoretical foundation needed to treat excited states via the equation of
motion (EOM) approach using these ground state CC methods. As these ground state
approximations to CCSD share its property of being exact for two-electron
systems, so will their excited state extensions. These methods are tested for two
complementary benchmark sets of excited states for a wide range of organic
molecules with focus on singlet and triplet excited states of both valence and
Rydberg nature. We also test these methods for doubly excited states, taking CH+
as an example to test their performance at equilibrium and stretched bond
geometries. Finally, we assess if any of these methods perform consistently
better than EOM CCSD.
PMID- 28411590
TI - Effects of ordered islands on surface resistivity: Ni on Au(111).
AB - The change in surface resistivity due to the formation of nickel islands on
gold(111) was studied by measuring the resistance of a thin film of Au as a
function of Ni coverage, theta. Previous studies showed that the Au(111)
herringbone reconstruction provides a template for the periodic growth of ordered
islands. Ni islands grow radially until theta ~ 0.3 ML, after which subsequent Ni
atoms contribute primarily to a second layer. Since Ni atoms on Au(111) grow in
ordered nanoclusters, a nonlinear dependence of resistance on theta might be
anticipated. Our results, however, show a linear dependence for Ni atoms in the
first layer, as if they were independent point scatterers. Above theta ~ 0.3 ML,
there is little change in resistivity, which we attribute to Ni atoms in the
second layer making no significant contribution to the resistivity. Although we
did not directly image the islands, our results are consistent with the growth
model and structures previously observed with scanning tunneling microscopy. Our
results serve as an indirect probe of the growth kinetics of this system, as well
as determining the contributions of Ni islands to the surface resistivity of the
Au film.
PMID- 28411591
TI - Analysis of the second harmonic generation signal from a liquid/air and
liquid/liquid interface.
AB - Three different liquid interfaces, water/air, thiophene/air, and water/thiophene,
were probed using the second harmonic generation (SHG) technique. Thiophene and
water have been chosen because the hyperpolarizability of these molecules has
already been measured or calculated and the different values can be found in
literature. We have studied the microscopic structure of these interfaces by
comparing the components of the second order susceptibility tensor determined
from the SHG polarization curve analysis with those determined via a molecular
dynamics (MD) simulation of these interfaces. We have indeed computed the
structure and orientation of water and thiophene molecules at the liquid/air and
liquid/liquid (L/L) interfaces as a function of the distance from the interface.
The integrated susceptibility values calculated by MD simulations agree well with
SHG results and validate the choice of force fields that should permit to
quantify more complex L/L interfaces.
PMID- 28411592
TI - On the accuracy of the LSC-IVR approach for excitation energy transfer in
molecular aggregates.
AB - We investigate the applicability of the linearized semiclassical initial value
representation (LSC-IVR) method to excitation energy transfer (EET) problems in
molecular aggregates by simulating the EET dynamics of a dimer model in a wide
range of parameter regime and comparing the results to those obtained from a
numerically exact method. It is found that the LSC-IVR approach yields accurate
population relaxation rates and decoherence rates in a broad parameter regime.
However, the classical approximation imposed by the LSC-IVR method does not
satisfy the detailed balance condition, generally leading to incorrect
equilibrium populations. Based on this observation, we propose a post-processing
algorithm to solve the long time equilibrium problem and demonstrate that this
long-time correction method successfully removed the deviations from exact
results for the LSC-IVR method in all of the regimes studied in this work.
Finally, we apply the LSC-IVR method to simulate EET dynamics in the
photosynthetic Fenna-Matthews-Olson complex system, demonstrating that the LSC
IVR method with long-time correction provides excellent description of coherent
EET dynamics in this typical photosynthetic pigment-protein complex.
PMID- 28411593
TI - High-resolution Fourier transform emission spectroscopy of the A~2Pii-X~2Pii band
of the OCS+ ion.
AB - High resolution Fourier transform emission spectroscopy of the A~2Pii-X~2Pii band
of the OCS+ ion was performed in the UV region to observe the nu1 (CO stretch)
progression bands (upsilon1 = 0 -> 2-5) for both the Omega=3/2 and 1/2 spin
components. Accurate molecular constants including the rotational constants, B0 =
0.194 765(13) and 0.187 106(13) cm-1, and the spin-orbit interaction constants,
A0 = -381.0(56) and -126.5(56) cm-1, were determined for the X~2Pi and A~2Pi
states, respectively, by the simultaneous analysis of the observed progression
bands. The CO bond length (rCO = 1.2810 A) for the A~2Pi state, derived from the
rotational constant B0 and Franck-Condon factors, is longer by 0.1756 A than that
(1.1054 A) for the X~2Pi state, while the CS bond length for the A~2Pi state is
shorter by 0.0905 A than that for the X~2Pi state. Pure rotational transition
frequencies in the ground X~2Pi state are predicted, as well as transition
frequencies of the nu1 fundamental band, with the present molecular constants.
PMID- 28411594
TI - QED effects in 1s and 2s single and double ionization potentials of the noble
gases.
AB - We present calculations on the quantum electrodynamics (QED) effects in 1s and 2s
single and double ionization potentials of noble gases from Ne to Rn as
perturbations on relativistic four-component Dirac-Fock wavefunctions. The most
dominant effect originates from the self-energy of the core-electron that yields
corrections of similar order as the transverse interaction. For 1s ionization
potentials, a match within few eV against the known experimental values is
obtained, and our work reveals considerable QED effects in the photoelectron
binding energies across the periodic table-most strikingly even for Ne. We
perform power-law fits for the corrections as a function of Z and interpolate the
QED correction of ~-0.55 eV for S1s. Due to this, the K-edge electron spectra of
the third row and below need QED for a match in the absolute energy when using
state-of-the-art instrumentation.
PMID- 28411595
TI - Infrared absorption of methanol-water clusters (CH3OH)n(H2O), n = 1-4, recorded
with the VUV-ionization/IR-depletion technique.
AB - We recorded infrared (IR) spectra in the CH- and OH-stretching regions of size
selected clusters of methanol (M) with one water molecule (W), represented as
MnW, n = 1-4, in a pulsed supersonic jet using the photoionization/IR-depletion
technique. Vacuum ultraviolet emission at 118 nm served as the source of
ionization in a time-of-flight mass spectrometer to detect clusters MnW as
protonated forms Mn-1WH+. The variations in intensities of Mn-1WH+ were monitored
as the wavelength of the IR laser light was tuned across the range 2700-3800 cm
1. IR spectra of size-selected clusters were obtained on processing of the
observed action spectra of the related cluster-ions according to a mechanism that
takes into account the production and loss of each cluster due to IR
photodissociation. Spectra of methanol-water clusters in the OH region show
significant variations as the number of methanol molecules increases, whereas
those in the CH region are similar for all clusters. Scaled harmonic vibrational
wavenumbers and relative IR intensities predicted with the M06-2X/aug-cc-pVTZ
method for the methanol-water clusters are consistent with our experimental
results. For dimers, absorption bands of a structure WM with H2O as a hydrogen
bond donor were observed at 3570, 3682, and 3722 cm-1, whereas weak bands of MW
with methanol as a hydrogen-bond donor were observed at 3611 and 3753 cm-1. For
M2W, the free OH band of H2O was observed at 3721 cm-1, whereas a broad feature
was deconvoluted to three bands near 3425, 3472, and 3536 cm-1, corresponding to
the three hydrogen-bonded OH-stretching modes in a cyclic structure. For M3W, the
free OH shifted to 3715 cm-1, and the hydrogen-bonded OH-stretching bands became
much broader, with a weak feature near 3179 cm-1 corresponding to the symmetric
OH-stretching mode of a cyclic structure. For M4W, the observed spectrum agrees
unsatisfactorily with predictions for the most stable cyclic structure,
indicating significant contributions from branched isomers, which is distinctly
different from M5 of which the cyclic form dominates.
PMID- 28411596
TI - Anomalous sound attenuation in Voronoi liquid.
AB - The physics of simple fluids in the hydrodynamic limit and notably the connection
between the proper microscopic scales and the macroscopic hydrodynamical
description are nowadays well understood. In particular, the three peak shape of
the dynamical structure factor S(k,omega) is a universal feature, as well as the
k-dependence of the peak position (?k) and width ?k2, the latter accounting for
the sound attenuation rate. In this paper, we present a theoretical model of
monodisperse fluid, whose interactions are defined via the Voronoi tessellations
of the configurations [called the Voronoi liquid and first studied in Ruscher et
al., Europhys. Lett. 112, 66003 (2015)], which displays at low temperatures a
marked violation of the universal features of S(k,omega) with a sound attenuation
rate only ?k. This anomalous behaviour, which apparently violates the basic
symmetries of the liquid state, is traced back to the existence of a time scale
which is both short enough for the viscoelastic features of the liquid to impact
the relaxational dynamics and however long enough for the momentum diffusion to
be substantially slower than the sound propagation on that characteristic time.
PMID- 28411597
TI - A diabatization protocol that includes spin-orbit coupling.
AB - A diabatization protocol that combines the recently developed model space
diabatization scheme and a mean-field treatment for spin-orbit coupling is
presented. The protocol is highly efficient and easy to use. Its robustness is
demonstrated in the calculations of the diabatic spin-orbit matrix elements of
PH3+, AsH3+, and SbH3+. It captures subtle geometry-dependence of the spin-orbit
couplings and provides wave function information to explain the origin of the
dependence.
PMID- 28411598
TI - Designing pairwise interactions that stabilize open crystals: Truncated square
and truncated hexagonal lattices.
AB - Using a recently introduced formulation of the ground-state inverse design
problem for a targeted lattice [W. Pineros et al., J. Chem. Phys. 144, 084502
(2016)], we discover purely repulsive and isotropic pair interactions that
stabilize low-density truncated square and truncated hexagonal crystals, as well
as promote their assembly in Monte Carlo simulations upon isochoric cooling from
a high-temperature fluid phase. The results illustrate that the primary challenge
to stabilizing very open two-dimensional lattices is to design interactions that
can favor the target structure over competing stripe microphases.
PMID- 28411599
TI - Bloch oscillations in organic and inorganic polymers.
AB - The transport of polarons above the mobility threshold in organic and inorganic
polymers is theoretically investigated in the framework of a one-dimensional
tight-binding model that includes lattice relaxation. The computational approach
is based on parameters for which the model Hamiltonian suitably describes
different polymer lattices in the presence of external electric fields. Our
findings show that, above critical field strengths, a dissociated polaron moves
through the polymer lattice as a free electron performing Bloch oscillations.
These critical electric fields are considerably smaller for inorganic lattices in
comparison to organic polymers. Interestingly, for inorganic lattices, the free
electron propagates preserving charge and spin densities' localization which is a
characteristic of a static polaron. Moreover, in the turning points of the
spatial Bloch oscillations, transient polaron levels are formed inside the band
gap, thus generating a fully characterized polaron structure. For the organic
case, on the other hand, no polaron signature is observed: neither in the shape
of the distortion-those polaron profile signatures are absent-nor in the energy
levels-as no such polaron levels are formed during the simulation. These results
solve controversial aspects concerning Bloch oscillations recently reported in
the literature and may enlighten the understanding about the charge transport
mechanism in polymers above their mobility edge.
PMID- 28411600
TI - CC2 oscillator strengths within the local framework for calculating excitation
energies (LoFEx).
AB - In a recent work [P. Baudin and K. Kristensen, J. Chem. Phys. 144, 224106
(2016)], we introduced a local framework for calculating excitation energies
(LoFEx), based on second-order approximated coupled cluster (CC2) linear-response
theory. LoFEx is a black-box method in which a reduced excitation orbital space
(XOS) is optimized to provide coupled cluster (CC) excitation energies at a
reduced computational cost. In this article, we present an extension of the LoFEx
algorithm to the calculation of CC2 oscillator strengths. Two different
strategies are suggested, in which the size of the XOS is determined based on the
excitation energy or the oscillator strength of the targeted transitions. The two
strategies are applied to a set of medium-sized organic molecules in order to
assess both the accuracy and the computational cost of the methods. The results
show that CC2 excitation energies and oscillator strengths can be calculated at a
reduced computational cost, provided that the targeted transitions are local
compared to the size of the molecule. To illustrate the potential of LoFEx for
large molecules, both strategies have been successfully applied to the lowest
transition of the bivalirudin molecule (4255 basis functions) and compared with
time-dependent density functional theory.
PMID- 28411601
TI - Kinetic Monte Carlo simulations of GaN homoepitaxy on c- and m-plane surfaces.
AB - The surface orientation can have profound effects on the atomic-scale processes
of crystal growth and is essential to such technologies as GaN-based light
emitting diodes and high-power electronics. We investigate the dependence of
homoepitaxial growth mechanisms on the surface orientation of a hexagonal crystal
using kinetic Monte Carlo simulations. To model GaN metal-organic vapor phase
epitaxy, in which N species are supplied in excess, only Ga atoms on a hexagonal
close-packed (HCP) lattice are considered. The results are thus potentially
applicable to any HCP material. Growth behaviors on c-plane (0001) and m-plane
(011-0) surfaces are compared. We present a reciprocal space analysis of the
surface morphology, which allows extraction of growth mode boundaries and direct
comparison with surface X-ray diffraction experiments. For each orientation, we
map the boundaries between 3-dimensional, layer-by-layer, and step flow growth
modes as a function of temperature and growth rate. Two models for surface
diffusion are used, which produce different effective Ehrlich-Schwoebel step-edge
barriers and different adatom diffusion anisotropies on m-plane surfaces.
Simulation results in agreement with observed GaN island morphologies and growth
mode boundaries are obtained. These indicate that anisotropy of step edge energy,
rather than adatom diffusion, is responsible for the elongated islands observed
on m-plane surfaces. Island nucleation spacing obeys a power-law dependence on
growth rate, with exponents of -0.24 and -0.29 for the m- and c-plane,
respectively.
PMID- 28411602
TI - Mapping the conformational free energy of aspartic acid in the gas phase and in
aqueous solution.
AB - The conformational free energy landscape of aspartic acid, a proteogenic amino
acid involved in a wide variety of biological functions, was investigated as an
example of the complexity that multiple rotatable bonds produce even in
relatively simple molecules. To efficiently explore such a landscape, this
molecule was studied in the neutral and zwitterionic forms, in the gas phase and
in water solution, by means of molecular dynamics and the enhanced sampling
method metadynamics with classical force-fields. Multi-dimensional free energy
landscapes were reduced to bi-dimensional maps through the non-linear
dimensionality reduction algorithm sketch-map to identify the energetically
stable conformers and their interconnection paths. Quantum chemical calculations
were then performed on the minimum free energy structures. Our procedure returned
the low energy conformations observed experimentally in the gas phase with
rotational spectroscopy [M. E. Sanz et al., Phys. Chem. Chem. Phys. 12, 3573
(2010)]. Moreover, it provided information on higher energy conformers not
accessible to experiments and on the conformers in water. The comparison between
different force-fields and quantum chemical data highlighted the importance of
the underlying potential energy surface to accurately capture energy rankings.
The combination of force-field based metadynamics, sketch-map analysis, and
quantum chemical calculations was able to produce an exhaustive conformational
exploration in a range of significant free energies that complements the
experimental data. Similar protocols can be applied to larger peptides with
complex conformational landscapes and would greatly benefit from the next
generation of accurate force-fields.
PMID- 28411603
TI - Determination of the bond dissociation energies of FeX and NiX (X = C, S, Se).
AB - The bond dissociation energies of FeC, NiC, FeS, NiS, FeSe, and NiSe have been
measured by the observation of a predissociation threshold in their resonant two
photon ionization spectra. Because the lowest separated atom limits generate a
vast number of potential energy curves, it is thought that the molecules
dissociate as soon as the ground separated atom limit is exceeded in energy. From
the observed thresholds, dissociation energies have been measured as D0(FeC) =
3.961(19), D0(NiC) = 4.167(3), D0(FeS) = 3.240(3), D0(NiS) = 3.651(3), D0(FeSe) =
2.739(6), and D0(NiSe) = 3.218(3) eV. Through the use of thermochemical cycles,
these values have been combined with other precisely known values to improve the
accuracy of other quantities, providing: D0(Fe+-C) = 4.270(19) eV, D0(Ni+-C) =
3.435(3) eV, IE(FeS) = 8.06(4) eV, IE(NiS) = 8.82(4) eV, and D0 (Fe-S-) =
2.92(10) or 2.89(10) eV, depending on the reference employed for EA(FeS-).
Comparisons to previous values are noted, when available. The periodic trends
observed are discussed in terms of a molecular orbital diagram for these species.
Finally, these results have also been used to calculate 0 K enthalpies of
formation of the gaseous MX molecules.
PMID- 28411604
TI - Ultrafast coherent energy transfer with high efficiency based on plasmonic
nanostructures.
AB - The theory of energy transfer dynamics of a pair of donor and acceptor molecules
located in the plasmonic hot spots is developed by means of the master equation
approach and the electromagnetic Green's tensor technique. A nonlocal effect has
been considered by using a hydrodynamic model. The coherent interaction between
the two molecules in plasmonic nanostructures is investigated, and we find that
the coupling strength between two molecules can be larger than dissipation. It is
shown that the energy transfer efficiency of a pair of molecules can be improved
largely and the transfer time decreases to dozens of femtoseconds when the
contribution of quantum coherence is considered. The physical origin for such a
phenomenon has also been analyzed. This ultrafast and high-efficiency energy
transfer mechanism could be beneficial for artificial light-harvesting devices.
PMID- 28411605
TI - Correlated natural transition orbitals for core excitation energies in multilevel
coupled cluster models.
AB - In this article, we present a black-box approach for the selection of orbital
spaces when computing core excitation energies in the multilevel coupled cluster
(MLCC) framework. Information available from the lower level of theory is used to
generate correlated natural transition orbitals (CNTOs) for the high-level
calculation by including both singles and doubles information in the construction
of the transition orbitals. The inclusion of the doubles excitation information
is essential to obtain a set of orbitals that all contain physical information,
in contrast to the natural transition orbitals where only a small subset of the
virtual orbitals contains physical information. The CNTOs may be included in an
active space based on a cutoff threshold for the eigenvalues corresponding to the
orbitals. We present MLCC results for core excitation energies calculated using
coupled cluster singles and doubles (CCSD) in the inactive space and CCSD with
perturbative triples (CC3) in the active space. The use of CNTOs results in small
errors compared to full CC3.
PMID- 28411606
TI - Mean-trajectory approximation for electronic and vibrational-electronic nonlinear
spectroscopy.
AB - Mean-trajectory approximations permit the calculation of nonlinear vibrational
spectra from semiclassically quantized trajectories on a single electronically
adiabatic potential surface. By describing electronic degrees of freedom with
classical phase-space variables and subjecting these to semiclassical
quantization, mean-trajectory approximations may be extended to compute both
nonlinear electronic spectra and vibrational-electronic spectra. A general mean
trajectory approximation for both electronic and nuclear degrees of freedom is
presented, and the results for purely electronic and for vibrational-electronic
four-wave mixing experiments are quantitatively assessed for harmonic surfaces
with linear electronic-nuclear coupling.
PMID- 28411607
TI - A simulation study on the phase behavior of hard rhombic platelets.
AB - Using Monte Carlo simulations, we investigate the phase behavior of hard rhombic
platelets as a function of the thickness of the platelets, T. The phase diagram
displays a columnar phase and a crystal phase in which the platelets are stacked
in columns that are arranged in a two-dimensional lattice. We find that the shape
of the platelets determines the symmetry of the two-dimensional lattice, i.e.,
rhombic platelets form an oblique columnar phase and a simple monoclinic crystal
phase. For sufficiently thick platelets, i.e., for a thickness-to-length ratio
T/L>0.17, we find only an isotropic fluid, an oblique columnar phase, and a
monoclinic crystal phase. Surprisingly, for an intermediate plate thickness,
0.083=9) is found due to a common spatial
distribution of the wave functions involved with the first dark exciton and the
first bright exciton, which are characterized primarily by a number of the wave
function nodes. The exciton wave function as well as other properties of smaller
molecules of n = 7 and 8 is, on the contrary, size-sensitive, although and the
peak positions are essentially size-insensitive because of the cancellation of
size-dependence of exciton binding energy and orbital energy. Different size
sensitivity between absorption and fluorescence can thus be explained unless such
cancellation also occurs for fluorescence.
PMID- 28411614
TI - Small static electric field strength promotes aggregation-prone structures in
amyloid-beta(29-42).
AB - The formation of senile plaques in central neural system resulting from the
aggregation of the amyloid beta (Abeta) of 40 and 42 residues is one of the two
hallmarks of Alzheimer's disease. Numerous experiments and computational studies
have shown that the aggregation of Abeta peptides in vitro is very complex and
depends on many factors such as pH, agitation, temperature, and peptide
concentration. The impact of a static electric field (EF) on amyloid peptide
aggregation has been much less studied, although EFs may have some applications
to treat Parkinson's disease symptoms. Here, we study the influence of an EF
strength of 20 mV/nm, present in the human brains, on the conformation of the
Abeta29-42 dimer. Our 7 MUs non-equilibrium atomistic simulations in aqueous
solution show that this field-strength promotes substantially the formation of
beta-hairpins, believed to be a very important intermediate state during
aggregation. This work also suggests that structural biology experiments
conducted under appropriate EF strengths may help reduce the conformational
heterogeneity of Abeta1-40/Abeta1-42 dimers and provide significant insights into
their structures that may be disease-causing.
PMID- 28411615
TI - Water/ice phase transition: The role of zirconium acetate, a compound with ice
shaping properties.
AB - Few compounds feature ice-shaping properties. Zirconium acetate is one of the
very few inorganic compounds reported so far to have ice-shaping properties
similar to that of ice-shaping proteins, encountered in many organisms living at
low temperature. When a zirconium acetate solution is frozen, oriented and
perfectly hexagonal ice crystals can be formed and their growth follows the
temperature gradient. To shed light on the water/ice phase transition while
freezing zirconium acetate solution, we carried out differential scanning
calorimetry measurements. From our results, we estimate how many water molecules
do not freeze because of their interaction with Zr cations. We estimate the
colligative properties of the Zr acetate on the apparent critical temperature. We
further show that the phase transition is unaffected by the nature of the base
which is used to adjust the pH. Our results provide thus new hints on the ice
shaping mechanism of zirconium acetate.
PMID- 28411616
TI - Experimental scaling of plane-Born cross sections and ab initio assignments for
electron-impact excitation and dissociation of XF4 (X = C, Si, and Ge) molecules.
AB - Electron energy loss spectra of carbon tetrafluoride, silicon tetrafluoride, and
germanium tetrafluoride molecules (CF4, SiF4, and GeF4) have been measured for
incident electron energies of 50-360 eV at 1.5 degrees -15.5 degrees and for 30
eV and 30 degrees scattering angle, while sweeping the energy loss over the
range 9.0-20.0 eV. Low-lying valence excited triplet and singlet states are
investigated by quantum chemical ab initio calculations. The Rydberg series
converging to the (lowest) ionisation energy limits of XF4 (X = C, Si, Ge) are
also identified and classified using the systematic behaviour according to the
magnitude of the quantum defects. A generalized oscillator strength analysis is
employed to derive oscillator strength f0 value and the apparent Born integral
cross sections from the corresponding differential cross sections by using the
Vriens formula for the optically allowed transitions. The f0 value is compared
with the optical oscillator strength of the photoabsorption, pseudo-photon
measurements, and theoretical values. The binary-encounter and f-scaled Born
cross sections of the most intense optically allowed transitions have been also
derived from the excitation threshold to the high energy region where the Born
approximation is valid. Potential energy curves were obtained along the XF3 + F
coordinate with two different basis sets to lend support on electron impact
dissociation processes yielding radical formation. We found that in CF4, the
lowest-lying dissociative character is due to intramolecular conversion from
Rydberg 3s to valence character (sigma*(C-F)), whereas in SiF4 and GeF4, an
antibonding behaviour prevails.
PMID- 28411617
TI - Temperature of maximum density and excess properties of short-chain alcohol
aqueous solutions: A simplified model simulation study.
AB - We perform an extensive computational study of binary mixtures of water and short
chain alcohols resorting to two-scale potential models to account for the
singularities of hydrogen bonded liquids. Water molecules are represented by a
well studied core softened potential which is known to qualitatively account for
a large number of water's characteristic anomalies. Along the same lines, alcohol
molecules are idealized by dimers in which the hydroxyl groups interact with each
other and with water with a core softened potential as well. Interactions
involving non-polar groups are all deemed purely repulsive. We find that the
qualitative behavior of excess properties (excess volume, enthalpy, and constant
pressure heat capacity) agrees with that found experimentally for alcohols such
as t-butanol in water. Moreover, we observe that our simple solute under certain
conditions acts as a "structure-maker," in the sense that the temperature of
maximum density of the bulk water model increases as the solute is added, i.e.,
the anomalous behavior of the solvent is enhanced by the solute.
PMID- 28411618
TI - An improved spin-orbit coupling model for use within the effective relativistic
coupling by asymptotic representation (ERCAR) method.
AB - An improved atomic spin-orbit model is presented, which is designed to be used
within the framework of the effective relativistic coupling by asymptotic
representation method. This method is used for the generation of highly accurate
coupled potential energy surfaces (PESs) to represent the fine structure energies
of appropriate systems. The approach is demonstrated using CH3I and its
photodissociation as a typical example. The method is based on a specific
diabatization of electronic spin-space ("spin-free") states with respect to the
asymptote at which a single relativistic atom is separated from a molecular non
relativistic fragment. Thus, the relativistic coupling effects can be treated
entirely within the atomic framework. So far, an effective spin-orbit coupling
operator which only accounts for intra-state coupling within each atomic spin
space state was used. In the present work, this approach is extended to account
for inter-state couplings among different atomic spin-space states as well. It is
shown that this extended approach improves the accuracy of the PESs significantly
for higher excited states and also enhances the accuracy of low energy states. In
particular, it improves the representation of the spin-orbit induced conical
intersection among the 3Q0 and 1Q1 states of CH3I, which is of high relevance for
the nonadiabatic quantum dynamics of the photodissociation.
PMID- 28411619
TI - Statistical properties of fluctuating enzymes with dynamic cooperativity using a
first passage time distribution formalism.
AB - We study the temporal fluctuations in catalytic rates for single enzyme reactions
undergoing slow transitions between two active states. We use a first passage
time distribution formalism to obtain the closed-form analytical expressions of
the mean reaction time and the randomness parameter for reaction schemes where
conformational fluctuations are present between two free enzyme conformers. Our
studies confirm that the sole presence of free enzyme fluctuations yields a non
Michaelis-Menten equation and can lead to dynamic cooperativity. The randomness
parameter, which is a measure of the dynamic disorder in the system, converges to
unity at a high substrate concentration. If slow fluctuations are present between
the enzyme-substrate conformers (off-pathway mechanism), dynamic disorder is
present at a high substrate concentration. Our results confirm that the dynamic
disorder at a high substrate concentration is determined only by the slow
fluctuations between the enzyme-substrate conformers and the randomness parameter
is greater than unity. Slow conformational fluctuations between free enzymes are
responsible for the emergence of dynamic cooperativity in single enzymes. Our
theoretical findings are well supported by comparison with experimental data on
the single enzyme beta-galactosidase.
PMID- 28411620
TI - Ordering of anisotropic nanoparticles in diblock copolymer lamellae: Simulations
with dissipative particle dynamics and a molecular theory.
AB - Local distribution and orientation of anisotropic nanoparticles in microphase
separated symmetric diblock copolymers has been simulated using dissipative
particle dynamics and analyzed with a molecular theory. It has been demonstrated
that nanoparticles are characterized by a non-trivial orientational ordering in
the lamellar phase due to their anisotropic interactions with isotropic monomer
units. In the simulations, the maximum concentration and degree of ordering are
attained for non-selective nanorods near the domain boundary. In this case, the
nanorods have a certain tendency to align parallel to the interface in the
boundary region and perpendicular to it inside the domains. Similar orientation
ordering of nanoparticles located at the lamellar interface is predicted by the
molecular theory which takes into account that the nanoparticles interact with
monomer units via both isotropic and anisotropic potentials. Computer simulations
enable one to study the effects of the nanorod concentration, length, stiffness,
and selectivity of their interactions with the copolymer components on the phase
stability and orientational order of nanoparticles. If the volume fraction of the
nanorods is lower than 0.1, they have no effect on the copolymer transition from
the disordered state into a lamellar microstructure. Increasing nanorod
concentration or nanorod length results in clustering of the nanorods and
eventually leads to a macrophase separation, whereas the copolymer preserves its
lamellar morphology. Segregated nanorods of length close to the width of the
diblock copolymer domains are stacked side by side into smectic layers that fill
the domain space. Thus, spontaneous organization and orientation of nanorods
leads to a spatial modulation of anisotropic composite properties which may be
important for various applications.
PMID- 28411621
TI - On the magnetic circular dichroism of benzene. A density-functional study.
AB - Spectroscopy of magnetic circular dichroism (MCD) provides enhanced information
on molecular structure and a more reliable assignment of spectral bands than
absorption alone. Theoretical modeling can significantly enhance the information
obtained from experimental spectra. In the present study, the time dependent
density functional theory is employed to model the lowest-energy benzene
transitions, in particular to investigate the role of the Rydberg states and
vibrational interference in spectral intensities. The effect of solvent is
explored on model benzene-methane clusters. For the lowest-energy excitation, the
vibrational sub-structure of absorption and MCD spectra is modeled within the
harmonic approximation, providing a very good agreement with the experiment. The
simulations demonstrate that the Rydberg states have a much stronger effect on
the MCD intensities than on the absorption, and a very diffuse basis set must be
used to obtain reliable results. The modeling also indicates that the Rydberg
like states and associated transitions may persist in solutions. Continuum-like
solvent models are thus not suitable for their modeling; solvent-solute clusters
appear to be more appropriate, providing they are large enough.
PMID- 28411622
TI - Modelling oxide formation and growth on platinum.
AB - We present a mathematical model of oxide formation and growth on platinum. The
motivation stems from the necessity to understand platinum dissolution in the
cathode catalyst layer of polymer electrolyte fuel cells. As is known, platinum
oxide formation and reduction are strongly linked to platinum dissolution
processes. However, a consistent model of the oxidation processes on platinum
does not exist. Our oxide growth model links interfacial exchange processes
between platinum and oxygen ions with the transport of oxygen ion vacancies via
diffusion and migration. A parametric analysis is performed to rationalize vital
trends in oxide growth kinetics. The rate determining step of oxide formation and
growth is identified as the extraction of platinum atoms at the metal-oxide
interface. A kinetic effect is observed while adjusting the potential when
growing the oxide layer, and the solution indicates that a structural change
occurs at high potentials, around 1.5 VRHE. The model compares well to
experimental data for various materials from various sources.
PMID- 28411623
TI - Hemoptysis as primary manifestation in three women with choriocarcinoma with
pulmonary metastasis: a case series.
AB - BACKGROUND: Gestational choriocarcinoma is the most common gestational
trophoblastic neoplasia; it is often secondary to hydatidiform mole, as well as
to abortion, ectopic pregnancy, premature delivery, or term delivery.
Approximately 60% of patients with choriocarcinoma develop pulmonary metastases,
but for patients with a respiratory condition, choriocarcinoma with lung
metastasis is a relatively rare lung cancer diagnosis. Three cases of
choriocarcinoma with pulmonary metastasis who had the primary symptom of
hemoptysis are described. CASE PRESENTATION: This case report describes a 35-year
old Chinese woman of Han nationality, a 23-year-old Chinese woman of Han
nationality, and a 46-year-old Chinese woman of Han nationality whose primary
symptom was hemoptysis and different chest imaging manifestations; they were
finally diagnosed as having pulmonary metastatic choriocarcinoma. All patients
had low risk factors, including abortion, hydatidiform mole, and ectopic
pregnancy. Human chorionic gonadotropin played an important role in
choriocarcinoma diagnosis. CONCLUSIONS: Based on the diagnosis and treatment of
the three patients, we suggested that for women with pregnancy history and
hemoptysis (particularly in the presence of risk factors such as abortion,
hydatidiform mole, ectopic pregnancy, and >35-years old), choriocarcinoma may be
the possible diagnosis or at least the main differential diagnosis.
PMID- 28411624
TI - Adverse drug events observed in patients with type 2 diabetes mellitus treated
with 100 mg versus 300 mg canagliflozin: a systematic review and meta-analysis of
published randomized controlled trials.
AB - BACKGROUND: Nowadays, canagliflozin monotherapy, or in combination with other
oral hypoglycemic agents (OHAs), is often administered in patients who are
treated for type 2 diabetes mellitus (T2DM). Therefore, we aimed to
systematically compare the adverse drugs events (AEs) which were associated with
100 mg versus 300 mg canagliflozin respectively, using a large number of
randomized patients with T2DM which were obtained from published trials. METHODS:
Randomized controlled trials (RCTs) comparing 100 mg versus 300 mg canagliflozin
in patients who were treated for T2DM were searched from electronic databases.
AEs reported during a follow up period ranging from 12 to 104 weeks were
considered as the clinical endpoints in this analysis. We calculated odds ratios
(OR) with 95% confidence intervals (CIs) and the analyses were carried out by
RevMan 5 . 3 software. RESULTS: Ten trials involving a total number of 5394
patients (2604 patients who were treated with 100 mg canagliflozin and 2790
patients who were treated with 300 mg canagliflozin) were included. The current
results showed that serious AEs were not significantly higher in patients who
were treated by 300 mg canagliflozin, with OR: 1.01, 95% CI: 0.79-1.29; P = 0.93.
Also, a similar rate of death was observed in patients who were treated by either
100 or 300 mg canagliflozin with OR: 1.13, 95% CI: 0.43-2.94; P = 0.80. Urinary
tract infections, postural dizziness and hypoglycemia were also similarly
manifested, with OR: 0.93, 95% CI: 0.70-1.23; P = 0.61, OR: 1.51, 95% CI: 0.42
5.37; P = 0.53 and OR: 0.96, 95% CI: 0.81-1.13; P = 0.60 respectively. However,
drug discontinuation due to AEs significantly favored 100 mg canagliflozin only
during this unequal follow-up period with OR: 1.35, 95% CI: 1.06-1.72; P = 0.01,
but it was not significantly different when trials with similar follow-up periods
were analyzed. CONCLUSION: 300 mg canagliflozin was not associated with
significantly higher adverse events compared to 100 mg canagliflozin in those
patients who were treated for T2DM. However, because this result was partly
affected by other anti-diabetic medications which were included in the treatment
regimen, further studies based on patients who were treated strictly on
canagliflozin monotherapy should be recommended to completely solve this issue.
PMID- 28411625
TI - Rapid imaging and detection of circulating tumor cells using a wide-field
fluorescence imaging system.
AB - Circulating tumor cells (CTCs) provide potentially accessible in vivo sources of
metastatic cancer cells. As such, considerable focus has been placed on analyzing
the genetics of single-CTCs. Prior to these analyses, however, CTCs must first be
detected within the blood samples of cancer patients. Current methods for
detection of CTCs by fluorescence microscopy require the analysis of hundreds of
images per blood sample, making this a time-consuming process that creates a
bottleneck in CTC analysis. In this study, we therefore developed a wide-field
fluorescence imaging system for rapid CTC detection. For these analyses, CTCs
were first isolated using the microcavity array (MCA), a micro-sized filter for
CTC recovery that separates cells based on differences in cell size and
deformability. Notably, the proposed imaging system enabled rapid (~10 s)
visualization of all stained cells within the 6 mm * 6 mm MCA field via one-shot
imaging. Furthermore, the morphology of the cells in the resulting images
accurately reflected that observed by conventional microscopy. In total,
isolation and detection of CTCs using the MCA combined with our novel wide-field
fluorescence imaging system was achieved within 1 h. Thus, our proposed system
will provide rapid CTC detection system.
PMID- 28411626
TI - Quantitative determination of polysulfide in albumins, plasma proteins and
biological fluid samples using a novel combined assays approach.
AB - Hydrogen sulfide (H2S) signaling involves polysulfide (RSSnSR') formation on
various proteins. However, the current lack of sensitive polysulfide detection
assays poses methodological challenges for understanding sulfane sulfur
homeostasis and signaling. We developed a novel combined assay by modifying
Sulfide Antioxidant Buffer (SAOB) to produce an "Elimination Method of Sulfide
from Polysulfide" (EMSP) treatment solution that liberates sulfide, followed with
methylene blue (MB) sulfide detection assay. The combined EMSP-MB sulfide
detection assay performed on low molecular weight sulfur species showed that
sulfide was produced from trisulfide compounds such as glutathione trisulfide and
diallyl trisulfide, but not from the thiol compounds such as cysteine, cystine
and glutathione. In the case of plasma proteins, this novel combined detection
assay revealed that approximately 14.7, 1.7, 3.9, 3.7 sulfide mol/mol released
from human serum albumin, alpha1-anti-trypsin, alpha1-acid glycoprotein and
ovalbumin, respectively, suggesting that serum albumin is a major pool of
polysulfide in human blood circulation. Taken together with the results of
albumins of different species, the liberated sulfide has a good correlation with
cysteine instead of methionine, indicating the site of incorporation of
polysulfide is cysteine. With this novel sulfide detention assay, approximately
8,000, 120 and 1100 MUM of polysulfide concentrations was quantitated in human
healthy plasma, saliva and tear, respectively. Our promising polysulfide specific
detection assay can be a very important tool because quantitative determination
of polysulfide sheds light on the functional consequence of protein-bound
cysteine polysulfide and expands the research area of reactive oxygen to reactive
polysulfide species.
PMID- 28411627
TI - Combination of electrospray ionization, atmospheric pressure photoionization and
laser desorption ionization Fourier transform ion cyclotronic resonance mass
spectrometry for the investigation of complex mixtures - Application to the
petroleomic analysis of bio-oils.
AB - The comprehensive description of complex mixtures such as bio-oils is required to
understand and improve the different processes involved during biological,
environmental or industrial operation. In this context, we have to consider how
different ionization sources can improve a non-targeted approach. Thus, the
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been
coupled to electrospray ionization (ESI), laser desorption ionization (LDI) and
atmospheric pressure photoionization (APPI) to characterize an oak pyrolysis bio
oil. Close to 90% of the all 4500 compound formulae has been attributed to CxHyOz
with similar oxygen class compound distribution. Nevertheless, their relative
abundance in respect with their double bound equivalent (DBE) value has evidenced
significant differences depending on the ion source used. ESI has allowed
compounds with low DBE but more oxygen atoms to be ionized. APPI has demonstrated
the efficient ionization of less polar compounds (high DBE values and less oxygen
atoms). The LDI behavior of bio-oils has been considered intermediate in terms of
DBE and oxygen amounts but it has also been demonstrated that a significant part
of the features are specifically detected by this ionization method. Thus, the
complementarity of three different ionization sources has been successfully
demonstrated for the exhaustive characterization by petroleomic approach of a
complex mixture.
PMID- 28411628
TI - Accurate and sensitive determination of molar fractions of 13C-Labeled
intracellular metabolites in cell cultures grown in the presence of isotopically
labeled glucose.
AB - This work describes a methodology based on multiple linear regression and GC-MS
for the determination of molar fractions of isotopically-labeled intracellular
metabolites in cell cultures. Novel aspects of this work are: i) the calculation
of theoretical isotopic distributions of the different isotopologues from an
experimentally measured value of % 13C enrichment of the labeled precursor ii)
the calculation of the contribution of lack of mass resolution of the mass
spectrometer and different fragmentation mechanism such as the loss or gain of
hydrogen atoms in the EI source to measure the purity of the selected cluster for
each metabolite and iii) the validation of the methodology not only by the
analysis of gravimetrically prepared mixtures of isotopologues but also by the
comparison of the obtained molar fractions with experimental values obtained by
GC-Combustion-IRMS based on 13C/12C isotope ratio measurements. The method is
able to measure molar fractions for twenty-eight intracellular metabolites
derived from glucose metabolism in cell cultures grown in the presence of 13C
labeled Glucose. The validation strategies demonstrate a satisfactory accuracy
and precision of the proposed procedure. Also, our results show that the minimum
value of 13C incorporation that can be accurately quantified is significantly
influenced by the calculation of the spectral purity of the measured cluster and
the number of 13C atoms of the labeled precursor. The proposed procedure was able
to accurately quantify gravimetrically prepared mixtures of natural and labeled
glucose molar fractions of 0.07% and mixtures of natural and labeled glycine at
molar fractions down to 0.7%. The method was applied to initial studies of
glucose metabolism of different prostate cancer cell lines.
PMID- 28411629
TI - Fluorescence probe for hypochlorous acid in water and its applications for highly
lysosome-targetable live cell imaging.
AB - Hypochloric acid (HOCl) plays important roles in cell signaling and homeostasis,
such as anti-inflammation and immune regulation, pathogen response and so on.
Accordingly, direct detection of HOCl at the organelle level is important for
investigation of the complex contributions of HOCl to human health. In the
present study, a water soluble lysosome-targeting fluorescent probe Lyso-1
bearing a hydrazone moiety as a HOCl-responsive site and a morpholine unit as a
lysosomal-targeting group has been synthesized and evaluated for its ability to
image lysosomal HOCl. The probe Lyso-1, based on a novel HOCl-promoted hydrazone
oxidation strategy, showed a highly selective fluorescent off/on response to HOCl
with the various reactive oxygen species in water. With increasing amount of ClO-
from 0.5 to 2.5 MUM, a linear correlation between the fluorescence intensity (570
nm) of Lyso-1 and [ClO-] was found, and the regression equation was y = 96.65 +
110.2068[ClO-] with a linear coefficient R of 0.9920. The detection limit is
determined to be 60 nM. Lyso-1 demonstrated a perfect lysosomal targetable
ability, and was successfully applied to image of exogenous, endogenous produced
lysosomal HOCl in live L929 cells. The success of subcellular imaging indicated
that the lysosome-targetable probe Lyso-1 could be used in further applications
for the investigation of biological functions and pathological roles of HClO at
organelle levels.
PMID- 28411630
TI - An immunochromatographic assay for carcinoembryonic antigen on cotton thread
using a composite of carbon nanotubes and gold nanoparticles as reporters.
AB - This paper describes a low-cost, sensitive, visual and rapid
immunochromatographic assay method on cotton thread for carcinoembryonic antigen
(CEA) detection by using novel carbon nanotube/gold nanoparticles (CNT/GNPs)
nanocomposite reporter probe. CEA, a lung cancer protein biomarker, was used as
analyte to demonstrate the principle of the immunochromatographic assay on cotton
thread biosensor. In the presence of target CEA, the decreasing aggregation
amount of CNT/GNPs nanocomposite reporter probes on the test zone induced
directly readout by naked eye. Meanwhile, quantitative detection could be
performed conveniently with a commercial available scanner. The performance with
respect to sensitivity of the method was greatly improved by 2-3 magnitudes
comparing with traditional gold nanoparticles (GNPs) or carbon nanotubes (CNTs)
as reporter probe. Under optimal conditions, the biosensor was capable of
detecting 2.32 ng/mL CEA (S/N >= 3) which is sensitive enough for clinical
diagnosis. These results indicated the novel CNT/GNPs nanocomposite reporter
probe based immunochromatographic assay on cotton thread is particularly suitable
for point-of-care (POC) diagnostics in resource-limited regions.
PMID- 28411631
TI - Escherichia coli adhesive coating as a chiral stationary phase for open tubular
capillary electrochromatography enantioseparation.
AB - Bacteria, the microorganism with intrinsic chirality, have numerous fascinating
chiral phenomena such as various chirality-triggered biological processes and
behaviors. Herein, bacteria were firstly explored as novel chiral stationary
phases in open-tubular capillary electrochromatography (OT-CEC) for
enantioseparation of fluoroquinolone enantiomers and simultaneous separation of
six fluoroquinolone antibiotics. The model strain, i.e. non-pathogenic
Escherichia coli (E. coli) DH5alpha, was adhered onto the inner surface of
positively charged polyethyleneimine (PEI) modified capillaries based on the
bacterial adhesion characteristics and strong electrostatic interaction. The
morphology and thickness of the bacteria adhesive coatings in the capillary were
characterized by field emission scanning electron microscopy (FESEM) and atomic
force microscopy (AFM). Baseline separation of ofloxacin and partial separation
of lomefloxacin enantiomers could be achieved by the E. coli coated columns. The
preparation parameters including the coating time and concentration of bacteria
that affecting the chiral resolution were intensively investigated. The
electrophoretic parameters, including pH, buffer concentration and applied
voltage, were also optimized. The developed method was validated (linearity, LOD,
LOQ, intra-day, inter-day and column-to-column repeatability and recovery) and
successfully utilized for the quantitative analysis of ofloxacin enantiomers in
the ofloxacin tablets. Moreover, only a slight decrease in the separation
efficiency was observed after 90 consecutive runs on the E. coli@capillary. These
results demonstrated that bacteria are promising stationary phases for chiral
separation in CEC.
PMID- 28411632
TI - An ultra-specific and sensitive sandwich ELISA for imatinib using two anti
imatinib antibodies.
AB - The development of an immunoassay for a low-molecular-weight drug first requires
the identification of specific antibodies that do not cross-react with the drug's
metabolites. If two antibodies can simultaneously recognize the entire structure
of the drug, we can then utilize them to establish an ultra-specific sandwich
ELISA, free from interference due to the metabolic products of the drug. This
paper reports an ultra-specific and sensitive sandwich ELISA for determination of
the tyrosine kinase inhibitor imatinib using two anti-imatinib antibodies. The
anti-imatinib antibodies were obtained by two partial structures of imatinib as
haptens (2-(5-amino-2-methylanilino)-4-(3-pyridyl)pyrimidine and 4-{(4-methyl-1
piperazinyl)-methyl}-benzoate). Under optimized conditions, this sandwich ELISA
shows a linear detection range from 64 pg mL-1 to 8 ng mL-1, and a limit of
detection of approximately 64 pg mL-1 for 100-MUL samples. The ELISA is specific
to imatinib and while there was no cross-reactivity with the major metabolite N
desmethyl-imatinib, slight cross-reactivity was found with metabolite pyridine-N
oxide-imatinib. This assay demonstrated significantly lower cross-reactivity with
metabolites than competitive ELISAs. Using this assay, drug levels were easily
measured in rat blood after oral administration of imatinib via a single dose of
30 mg kg-1 or 100 mg kg-1. The levels in rat serum measured by this ELISA were
comparable with those measured by HPLC, and there was a strong correlation
between the values determined by the two methods (y = 0.983x + 0.081, R2 =
0.948). Thus, we have successfully developed the first specific and sensitive
sandwich ELISA for imatinib using two anti-imatinib antibodies. This sandwich
ELISA will be a valuable tool for therapeutic drug monitoring and pharmacokinetic
studies of imatinib.
PMID- 28411633
TI - Proximity hybridization-regulated catalytic DNA hairpin assembly for
electrochemical immunoassay based on in situ DNA template-synthesized Pd
nanoparticles.
AB - Novel hybridization proximity-regulated catalytic DNA hairpin assembly strategy
has been proposed for electrochemical immunoassay based on in situ DNA template
synthesized Pd nanoparticles as signal label. The DNA template-synthesized Pd
nanoparticles were characterized with atomic force microscopic and X-ray
photoelectron spectroscopy. The highly efficient electrocatalysis by DNA template
synthesized Pd nanoparticles for NaBH4 oxidation produced an intense detection
signal. The label-free electrochemical method achieved the detection of
carcinoembryonic antigen (CEA) with a linear range from 10-15 to 10-11 g mL-1 and
a detection limit of 0.43 * 10-15 g mL-1. Through introducing a supersandwich
reaction to increase the DNA length, the electrochemical signal was further
amplified, leading to a detection limit of 0.52 * 10-16 g mL-1. And it rendered
satisfactory analytical performance for the determination of CEA in serum
samples. Furthermore, it exhibited good reproducibility and stability; meanwhile,
it also showed excellent specificity due to the specific recognition of antigen
by antibody. Therefore, the DNA template synthesized Pd nanoparticles based
signal amplification approach has great potential in clinical applications and is
also suitable for quantification of biomarkers at ultralow level.
PMID- 28411634
TI - Encapsulating Proteins in Nanoparticles: Batch by Batch or One by One.
AB - Encapsulation of proteins in nanoparticles (NPs) can greatly improve the
properties of proteins such as their stability against denaturation and
degradation by proteases, and branches out the applications of natural proteins
from their intrinsic localizations and functions in living organisms for
biomedical and industrial applications. We recently developed several methods to
armor proteins in NPs with sizes from nanometers up to >100nm, batch by batch or
one by one, covalently or noncovalently, for a wide range of applications from
biocatalysis to bioimaging and drug delivery. In this chapter, we provide
detailed protocols on these methods. Key steps of specific protocols are
explained with particular examples to help other laboratories to adopt and modify
these methods for their own purposes. The advantages and disadvantages of each
method are summarized, and guidelines for choosing the right method for a given
application, as well as the current challenges and future directions of this
field, are discussed.
PMID- 28411635
TI - Guide to the Preparation of Molecularly Imprinted Polymer Nanoparticles for
Protein Recognition by Solid-Phase Synthesis.
AB - Molecularly imprinted polymers (MIPs) are synthetic antibody mimics possessing
specific cavities designed for a target molecule. Nowadays, molecular imprinting
of proteins still remains a challenge as the generation of selective imprinted
cavities is extremely difficult, due to their flexible structure and the presence
of a multitude of functional sites. To overcome this difficulty, we propose a
solid-phase synthesis strategy to prepare MIPs specific for any protein that can
be immobilized in an oriented way on a solid support. Trypsin and kallikrein were
used as model proteins. The solid-phase support consists of glass beads
functionalized with two affinity ligands of the enzymes, the competitive
inhibitor p-aminobenzamidine to orient the enzymes via their active site, or a
Cu2+chelate to orient via the surface histidine residues of the enzyme.
Thermoresponsive molecularly imprinted polymer nanoparticles (MIP-NPs) are then
synthesized around the immobilized enzyme. The MIP-NPs are released by a simple
temperature change, resulting in protein-free polymers endowed with improved
binding site homogeneity since all binding sites have the same orientation. The
MIP-NPs exhibit apparent dissociation constants between 0.02 and 2nM toward their
target proteins, which is comparable to those of natural antibodies. Moreover,
these water-compatible polymers, targeting different domains of the enzyme, can
also function as protective agents (armor), hence preventing the target proteins
from denaturation by heat or pH.
PMID- 28411636
TI - Armored Urease: Enzyme-Bioconjugated Poly(acrylamide) Hydrogel as a Storage and
Sensing Platform.
AB - Jack bean urease is an important enzyme not only because of its numerous uses in
medical and other fields but also because of its historical significance-the
first enzyme to be crystallized and also the first nickel metalloenzyme. This
enzyme hydrolyzes urea into ammonia and carbon dioxide; however, the stability of
this enzyme at ambient temperature is a bottleneck for its applicability. To
improve urease stability, it was immobilized on different substrates,
particularly on polymeric hydrogels. In this study, the enzyme was coupled
covalently with poly(acrylamide) hydrogel with an yield of 18MUmol/cm3. The
hydrogel served as the nanoarmor and protected the enzyme against denaturation.
The enzyme immobilized on the polymer hydrogel showed no loss in activity for
more than 30 days at ambient temperature, whereas free enzyme lost its activity
within a couple of hours. The Michaelis-Menten constant (Km) for free and
immobilized urease were 0.0256 and 0.2589mM, respectively, on the first day of
the study. The Km of the immobilized enzyme was approximately 10 times higher
than that of the free enzyme. The hydrogel technique was also used to prepare
light diffracting polymerized colloidal crystal array in which urease enzyme was
covalently immobilized. This system was applied for the detection of mercury
(Hg2+) with the lower limit as 1ppb, which is below the maximum contaminant limit
(2ppb) for mercury ions in water. The experimental details of these studies are
presented in this chapter.
PMID- 28411637
TI - Armored Enzyme-Nanohybrids and Their Catalytic Function Under Challenging
Conditions.
AB - Synthesis and characterization of highly stable and functional bienzyme-polymer
triads assembled on layered graphene oxide (GO) are described here. Glucose
oxidase (GOx) and horseradish peroxidase (HRP) were used as model enzymes and
polyacrylic acid (PAA) as model polymer to armor the enzymes. PAA-armored GOx and
HRP covalent conjugates were further protected from denaturation by adsorption
onto GO nanosheets. Structure and morphology of this enzyme-polymer-nanosheet
hybrid biocatalyst (GOx-HRP-PAA/GO) were confirmed by agarose gel
electrophoresis, zeta potential, circular dichroism, and transmission electron
microscopy. The armored biocatalysts retained full enzymatic activities under
challenging conditions of pH (2.5-7.4), warm temperatures (65 degrees C), and
presence of chemical denaturants, 4mM sodium dodecyl sulfate, while GOx/HRP
physical mixtures without the armor had very little activity under the same
conditions. Therefore, this novel combination of two orthogonal approaches,
enzyme conjugation with PAA and subsequent physical adsorption onto GO
nanosheets, resulted in super stable hybrid biocatalysts that function under
harsh conditions. Therefore, this general and powerful approach may be used to
design environmentally friendly, green, biocompatible, and biodegradable
biocatalysts for energy production in biofuel cell or biobattery applications.
PMID- 28411638
TI - Approaches for Conjugating Tailor-Made Polymers to Proteins.
AB - A series of methods are outlined for attaching functional polymers to proteins.
Polymers with good control over structure, functionality, and composition can be
created using reversible addition-fragmentation chain transfer (RAFT)
polymerization. These polymers can be covalently linked to enzymes and proteins
using either the "grafting-to" approach, where a preformed polymer is attached to
the protein surface, or the "grafting-from" approach, where the polymer is grown
from the protein surface. Methods for grafting-to, or attaching the RAFT chain
transfer agent to the protein surface outlined include the commonly used
carbodiimide/activated ester (EDC/NHS) coupling. Methods are also outlined to
graft-from the surface of the protein using RAFT polymerization. Additionally, it
is possible to site specifically introduce a reactive azide group to the protein
surface using enzymatic ligation as a posttranslational modification. This
reactive azide group can be conjugated to an alkyne-containing polymer using
highly efficient click chemistry. These robust protocols can produce protein
polymer conjugates with various architectures and functionalities. Methods are
also outlined for characterization of the resulting bioconjugates.
PMID- 28411639
TI - NanoArmoring of Enzymes by Polymer-Functionalized Iron Oxide Nanoparticles.
AB - Polymer-armored enzymes loaded onto magnetic nanoparticles, as efficient
nanobioreactors with enhanced properties, are described in this chapter. Polymers
are useful macromolecules carrying a large number of surface charges and
repeating units of desired chemical functional groups for linking enzymes onto
them. Magnetic micro/nanoparticles have been widely used as enzyme carriers with
the incorporation of suitable polymer layers. Synthesized iron oxide magnetic
nanoparticles have been used to immobilize a peroxide-catalyzing enzyme-like heme
protein: myoglobin using covalent and noncovalent strategies. The stability,
scalability, and kinetics of the conjugate were studied in detail using
spectroscopic and electrochemical analysis. Compared to the free myoglobin in
solution, myoglobin conjugated to magnetic nanoparticles demonstrated high
catalytic stability and easy recovery from the reaction medium for further use.
Due to the large surface area offered by the magnetic nanoparticles, a large
amount of myoglobin could be loaded with a small amount of magnetic
nanoparticles. Selected examples of polymer-enzyme and polymer-magnetic
nanoparticle-enzyme conjugates developed by us and others are presented in this
chapter, and representative methods for making cost-effective scalable and
reusable enzymatic reactors have been described.
PMID- 28411640
TI - Expression of Cellulolytic Enzyme as a Fusion Protein That Reacts Specifically
With a Polymeric Scaffold.
AB - The formation of higher-order assemblies of multiple proteins or enzymes is a
general mechanism to achieve more sophisticated biological function in biological
systems. For example, cellulosomes are large complexes consisting of multiple
cellulolytic enzymes that rely on the concerted actions of different enzymes
built onto a common protein scaffold to facilitate the breakdown of the polymeric
substrate, cellulose. One strategy for mimicking these highly effective
nanomachines may involve the use of synthetic scaffolds that can react to and
organize multiple engineered enzymes to promote synergistic action between the
enzymes on the scaffold. As an example of the earlier strategy, we describe here
an approach for the expression of cellulolytic enzymes with a serine esterase
tag, and the rapid reaction between the tag and the end-functionalized polymers
to form enzyme-polymer-enzyme multienzyme conjugates. In principle, this general
and versatile supramolecular approach may be used to organize specific
cellulolytic enzymes onto synthetic scaffolds to form multienzyme complexes to
potentially work in synergy for enhanced biological activities. Best reaction
conditions, good activities of the armored cellulolytic enzymes and the design of
optimal protein linker in the fusion protein are discussed in detail. If other
reactive tags are included on the enzyme in future, multiple types of synergistic
enzymes may be positioned at specific sites on a designed polymer scaffold that
mimics the complex structure and enhanced function of natural cellulosomes. This
type of nanoarmoring of multiple enzymes on a nanoscale might also enhance enzyme
stability, when compared to the unprotected enzymes.
PMID- 28411641
TI - Nanoarmoring of Proteins by Conjugation to Block Copolymer Micelles.
AB - The creation of polymer nanoparticles with protein functionality is of great
interest to many applications such as targeted drug or gene delivery, diagnostic
imaging, cancer theranostics, delivery of protein therapeutics, sensing chemical
and biomolecular analytes in complex environments, and design of protective
clothing resembling a second skin. Many approaches to achieving this goal are
being explored in the current literature. In this chapter, we describe a
relatively simple and flexible approach of conjugating the protein to an
amphiphilic block copolymer and creating polymer nanoparticles with protein
functionality by taking advantage of the intrinsic self-assembly behavior of the
amphiphilic block copolymer. The commercially available and biocompatible
polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer is
used as the polymer building block. For demonstrative purposes, bovine serum
albumin was chosen as the protein. We determine the molecular weight of the
protein-polymer conjugate and thereby the degree of conjugation using sodium
dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry measurements. Retention of
protein secondary structure in the conjugate was determined by circular dichroism
spectroscopy, and the biological activity of the protein in the conjugated state
has been evaluated by kinetic assay involving hydrolysis of an organophosphate
compound. Dynamic light scattering and zeta potential measurements were used to
characterize the size and charge of the protein-polymer conjugate micelle.
Precise control of the size of the micelle and surface number density of the
proteins on the micelle surface by coassembling with a second block copolymer
have been demonstrated. These studies document a rational approach to armor the
protein by conjugation with a block copolymer micelle, as a general approach.
PMID- 28411642
TI - Semisynthetic Enzymes by Protein-Peptide Site-Directed Covalent Conjugation:
Methods and Applications.
AB - This chapter describes the rational design and synthesis of semisynthetic lipases
by site-directed incorporation of tailor-made peptides on the lipase-lid site to
improve its activity, specificity, and enantioselectivity in specific
biotransformations. Cysteine was genetically introduced at a particular point of
the oligopeptide lid of the enzyme, and cysteine-containing peptides,
complementary to the amino acid sequence on the lid site of Geobacillus
thermocatenulatus lipase (BTL), were covalently attached on the lid of two
different cysteine-BTL variants based on a fast thiol-disulfide exchange ligation
followed by desulfurization. The BTL variants were initially immobilized on solid
support to introduce the advantages of solid-state chemistry, such as
quantitative transformations, easy purification, and recyclability. In the two
different immobilized variants BTL-A193C and BTL-L230C, the cysteine was then
activated with 2-dipyridyldisulfide to help the disulfide exchange with the
peptide, generating the semisynthetic enzyme in high yield. Excellent results of
improvement of activity and selectivity were obtained. For example, the peptide
BTL conjugate (at position 193) was 40-fold more active than the corresponding
unmodified enzyme for the hydrolysis of per-acetylated thymidine at pH 5, or
fourfold in the desymmetrization of dimethyl-3-phenylglutarate at pH 7. The new
enzyme also exhibited excellent enantioselectivity in the desymmetrization
reaction with enantiomeric excess (ee) of >99% when compared to that of the
unmodified enzyme (ee=78%).
PMID- 28411643
TI - Transgultaminase-Mediated Nanoarmoring of Enzymes by PEGylation.
AB - PEGylation, the covalent attachment of polyethylene glycol to bioactive
molecules, is one of the leading approaches used to prolong pharmacokinetics, to
improve the stability, and to reduce the immunogenicity of therapeutic proteins.
PEG-conjugated products are associated with better therapy outcomes and improved
patient compliance. Widely applied in clinical practice, the technology is mainly
used to modify proteins, peptides, and oligonucleotides but also other drug
delivery systems such as the liposomal one. Undergoing continuous attempts to
optimize therapeutic efficacy and to tune the formation of conjugates, a number
of different PEGylation processes are now available to researchers for protein
conjugation. Although the possibility of obtaining highly homogeneous conjugate
mixtures, preferably formed by a single monoconjugate, from a chemical
conjugation reaction continues to be limited, several enzymatic conjugation
approaches have recently been investigated to address this need. PEGylation
mediated by microbial transglutaminase and its many advantages and modifications
are outlined in detail in the current work permitting interested readers to
perform site-specific protein derivatization to glutamines or lysines.
PMID- 28411644
TI - Enzyme Adsorption on Nanoparticle Surface Probed by Highly Sensitive Second
Harmonic Light Scattering.
AB - Recent developments in second harmonic light scattering technique and the
associated theoretical models have provided a deeper insight of molecular
interactions on micro- and nanoparticle surfaces. This technique is extended to
probe the thermodynamics of protein adsorption on nanoparticle surface which is
crucial for understanding the fate of nanoparticle-based formulations in
biomedical applications. A modified Langmuir adsorption model has been applied to
extract the thermodynamic parameters from the experimental data. The general
applicability of the technique is established by extracting free energy change,
association constant, and binding stoichiometry of adsorption of a moderate size
protein, alcohol dehydrogenase, and a small size protein, insulin, on gold
nanoparticles. The free energy change for the adsorption is found to be of the
order of -55kJ/mol, which indicates that the interaction of proteins with the
nanoparticle surface involves weak forces. On the other hand, the low value of
the free energy change makes the detachment of the protein from the particle
surface easier and guarantees reversibility of the binding process. In addition,
one gets the binding stoichiometry of the proteins with the nanoparticle surface
which opens up the possibility of controlling the payload of the protein- or
peptide-based therapeutics in future biomedical applications.
PMID- 28411645
TI - Polymer-Based Protein Engineering: Synthesis and Characterization of Armored,
High Graft Density Polymer-Protein Conjugates.
AB - Atom transfer radical polymerization (ATRP) from the surface of a protein can
generate remarkably dense polymer shells that serve as armor and rationally tune
protein function. Using straightforward chemistry, it is possible to covalently
couple or display multiple small molecule initiators onto a protein surface. The
chemistry is fine-tuned to be sequence specific (if one desires a single targeted
site) at controlled density. Once the initiator is anchored on the protein
surface, ATRP is used to grow polymers on protein surface, in situ. The technique
is so powerful that a single-protein polymer conjugate molecule can contain more
than 90% polymer coating by weight. If desired, stimuli-responsive polymers can
be "grown" from the initiated sites to prepare enzyme conjugates that respond to
external triggers such as temperature or pH, while still maintaining enzyme
activity and stability. Herein, we focus mainly on the synthesis of chymotrypsin
polymer conjugates. Control of the number of covalently coupled initiator sites
by changing the stoichiometric ratio between enzyme and the initiator during the
synthesis of protein-initiator complexes allowed fine-tuning of the grafting
density. For example, very high grafting density chymotrypsin conjugates were
prepared from protein-initiator complexes to grow the temperature-responsive
polymers, poly(N-isopropylacrylamide), and poly[N,N'
dimethyl(methacryloyloxyethyl) ammonium propane sulfonate]. Controlled growth of
polymers from protein surfaces enables one to predictably manipulate enzyme
kinetics and stability without the need for molecular biology-dependent
mutagenesis.
PMID- 28411646
TI - Nano-Armoring of Enzymes: Rational Design of Polymer-Wrapped Enzymes.
AB - The formulation in which therapeutic proteins are administered plays a key role
in retaining their biological activity. Enzyme wrapping, using synthetic
polymers, is a strategy employed to provide enzymes with lower immunogenicity,
longer circulation times, and better targeting capabilities. Protein-polymer
complexation methods, involving covalent, noncovalent, and electrostatic
interactions, that can provide means to develop formulations for retaining enzyme
stability are discussed in this chapter. Amphiphilic self-cross-linkable polymer
was used to encapsulate capsase-3 enzyme in the nanogel, while inverse emulsion
polymerization method was used to entrap alpha-glucosidase enzyme in the nanogel.
These nanogels were characterized by dynamic light scattering, transmission
electron microscopy, and gel electrophoresis. Upon release of caspase-3 enzyme
from polymeric nanogel, it retained nearly 86% of its original activity.
Similarly, alpha-glucosidase that was encased in the acid cleavable polymeric
nanogel exhibited substantial activity after release under acidic conditions (pH
5, 48h). Nano-armoring of the enzymes were nearly complete and provided high
yields of the encased enzyme.
PMID- 28411647
TI - Nanoarmored Enzymes for Organic Enzymology: Synthesis and Characterization of
Poly(2-Alkyloxazoline)-Enzyme Conjugates.
AB - The properties of enzymes can be altered significantly by modification with
polymers. Numerous different methods are known to obtain such polymer-enzyme
conjugates (PECs). However, there is no universal method to render enzymes into
PECs that are fully soluble in organic solvents. Here, we present a method, which
achieves such high degree of modification of proteins that the majority of
modified enzymes will be soluble in organic solvents. This is achieved by
preparing poly(2-alkyloxazoline)s (POx) with an NH2 end group and coupling this
functional polymer via pyromellitic acid dianhydride onto the amino groups of the
respective protein. The resulting PECs are capable of serving as surfactants for
unmodified proteins, rendering the whole mixture organosoluble. Depending on the
nature of the POx and the molecular weight and the nature of the enzyme, the PECs
are soluble in chloroform or even toluene. Another advantage of this method is
that the poly(2-alkyloxazoline) can be activated with the coupling agent and used
for the enzyme conjugation without further purification. The POx-enzyme
conjugates generated by this modification strategy show modulated catalytic
activity in both, aqueous and organic, systems.
PMID- 28411648
TI - Preparation and Applications of Dendronized Polymer-Enzyme Conjugates.
AB - Dendronized polymer-enzyme conjugates are large, water-soluble macromolecular
structures built from a linear, fully synthetic, dendronized polymer (denpol),
and several copies of enzyme molecules covalently bound to the peripheral
functional groups of the denpol. Since denpol chains comprise repeating units
with regularly branched side chains (dendrons), denpols have a cylindrical shape
and are much thicker than conventional linear polymers. Depending on the dendron
generation and chemical structure, denpols may have a large number of functional
groups on their surface, exposed to the aqueous medium in which they are
dissolved. Enzymes (and also other molecules) can be attached to these functional
groups, for example, via a stable bis-aryl hydrazone (BAH) bond. The dendronized
polymer scaffold might also serve as a nanoarmor and stabilize the delicate
enzymes. One of the denpols which can be used for the preparation of denpol
enzyme conjugates is de-PG2. It has a poly(methacrylate) backbone and consists of
second-generation dendrons with four peripheral amino groups in each repeating
unit. The synthesis of de-PG2 and the preparation of a de-PG2 conjugate carrying
BAH-linked proteinase K (proK), as an example, are described here for
applications in the field of enzyme immobilization on solid surfaces. The
nanoarmored enzyme-polymer conjugate indicated high stability and retention of
enzymatic activity.
PMID- 28411649
TI - Nanoarmoring of Enzymes by Interlocking in Cellulose Fibers With Poly(Acrylic
Acid).
AB - A simple method for interlocking glucose oxidase (GOx) and horseradish peroxidase
(HRP) in cellulose fibers using poly(acrylic acid) (PAA) as an armor around the
enzyme, without any need for activation of the cellulose support, is reported
here. The resulting enzyme paper is an inexpensive, stable, simple, wearable, and
washable biosensor. PAA functions as a multifunctional tether to interlock the
enzyme molecules around the paper fibers so that the enzymes are protected
against thermal/chemical denaturation and not released from the paper when washed
with a detergent. The decreased conformational entropy of the interlocked enzyme
protected by the nanoarmor is likely responsible for increased enzyme stability
to heat and chemical denaturants (retained >=70 percent enzyme activity after
washing with urea or SDS for 30min), and the polymer protects the enzyme against
inactivation by proteases, bacteria, inhibitors, etc. The kinetics of the
interlocked enzyme were similar to that of the enzyme in solution. The Vmax was
6(+/-0.5)mM per minute before washing, then increased slightly to 9(+/-1.4)mM per
minute after washing with water. The Km was 22(+/-6.4mM), which was slightly
higher compared to GOx in solution (25-27mM). Because the surface area of the
paper does not limit the enzyme loading, about 20% of enzyme was successfully
loaded onto the paper (0.2g enzyme per gram of paper), and >=95% of the enzyme
was retained after washing. Interlocking works with other enzymes such as
laccase, where >=60% of the enzyme activity is retained. This novel methodology
provides a low cost, simple, modular approach of achieving high enzyme loadings
in ordinary filter paper, not limited by cellulose surface area, and there has
been no need for complex methods of enzyme engineering or toxic methods of
activation of the solid support to prepare highly active biocatalysts.
PMID- 28411650
TI - Armoring Enzymes by Metal-Organic Frameworks by the Coprecipitation Method.
AB - Enzymatic processes have great potential for applications in industrial
biocatalysis, biosensing, and biomedical engineering. However, poor stability and
difficulty in the reuse of enzymes still create challenges for their use in
catalysis and other applications. In recent years, enzyme-incorporated metal
organic frameworks (enzyme@MOF) have emerged as a new type of armored enzymes and
are thought to be an appealing solution to the above challenges. To date, the
preparation of enzyme-MOF composites can be divided into three categories,
including physical adsorption, covalent conjugation, and coprecipitation. The
coprecipitation method integrates the synthesis of MOFs and encapsulation of
enzymes into one step, allowing common MOFs with regular pore sizes to be used as
carriers for enzyme binding. In this chapter, we present a protocol for the
synthesis of enzyme@MOF composites using the coprecipitation approach with
particular details.
PMID- 28411651
TI - Enzyme Armoring by an Organosilica Layer: Synthesis and Characterization of
Hybrid Organic/Inorganic Nanobiocatalysts.
AB - The availability of highly stable and reusable enzymes is one of the main
challenges in bio-based industrial processes. Enzyme immobilization and
encapsulation represent promising strategies to reach this goal. In this chapter,
the synthetic strategy to produce hybrid organic/inorganic nanobiocatalysts (NBC)
is reported. This strategy is based on the sequential immobilization of an enzyme
on the surface of silica nanoparticles followed by the growth, at the surface of
the nanoparticles, of a shielding layer which serves as an armor to protect the
enzyme against denaturation/degradation. This armor is produced through a
thickness-controlled organosilane poly-condensation onto the nanoparticle surface
around the enzyme to form a protective organosilica layer. The armored
nanobiocatalysts present enhanced catalytic activity and improved stability
against heat, pH, chaotropic agents, proteases, and ultrasound. The method is
versatile in that it can be successfully adapted to a number of different
enzymes.
PMID- 28411652
TI - Strategies for Biophysical Characterization of Protein-Polymer Conjugates.
AB - Protein-polymer conjugates are increasingly viewed as promising avenues to
producing industrial enzymes with high activity capable of withstanding
potentially harsh reaction conditions, or to designing novel therapeutics with
triggered release, controlled masking, or increased resistance to proteolytic
degradation. Common among these applications are the desire to improve the
stability of protein-polymer conjugates to unfolding by exposure to chemicals or
thermal stress. Thus, assays that allow researchers to robustly and easily
characterize protein-polymer conjugates by obtaining thermodynamic parameters for
folding stand to play an important role in the development of improved protein
polymer conjugates. Herein, we describe two techniques, differential scanning
fluorimetry and intrinsic tryptophan fluorescence, used in our laboratories to
obtain thermodynamic parameters of unfolding that allow for direct comparison of
protein-polymer conjugates and the myriad effects of variations in attachment
site, polymer identity, and polymer length. These two experiments, which are
easily amenable to parallelization, are presented as high-throughput replacements
for more traditionally employed circular dichroism experiments and as complements
to functional chemical stability or functional thermal stability experiments.
Each assay is presented in a parallelized format that allows for rapid scaling
and high-throughput analysis of protein-polymer conjugate libraries. Descriptions
of the assays include a discussion of advantages and disadvantages alongside
protocol details and approaches to data analysis.
PMID- 28411653
TI - Preface.
PMID- 28411654
TI - ?
PMID- 28411655
TI - [A new cleansing technique for complex wounds].
AB - Fast, effective and pain-free cleansing is essential in the management of wounds,
in order to favour the formation of the granulation tissue and the filling of the
cavity. Faced with a chronic wound which was not progressing from the
inflammatory phase, caregivers put in place a technique combining negative
pressure therapy and instillations of sodium bicarbonate and oxygenated water.
The initial results are promising, with the patient benefiting from effective and
pain-free cleansing.
PMID- 28411656
TI - ?
PMID- 28411657
TI - [Suicide in France, a situational analysis].
AB - The fall in the number of suicides in France in no way diminishes the urgent need
to act and reinforce the efforts, initiatives and resources to fight against this
human tragedy. Public policies are starting to show results. The action of the
French national suicide watch, associations, health professionals as well as the
perspectives of the French national mental health council should amplify this
movement.
PMID- 28411658
TI - [Improving suicide prevention].
AB - Suicidal thoughts precede a suicide attempt. Knowing the people who are exposed
to such thoughts enables prevention to be improved. The results of a study of the
general population show that one in five French people claim to have already
seriously considered committing suicide. This represents a particularly
concerning public health issue.
PMID- 28411659
TI - [Suicide, a social fact].
AB - Treating suicide as a social fact means disregarding its individual and dramatic
dimensions. Sociologists do not reason on the basis of specific cases but by
studying the variations, in space and time, of suicide rates. Their contribution
relates essentially to a renewed perspective on society: suicide is in fact a
very accurate indicator of the intensity and quality of the bonds which unite or
isolate individuals in a society.
PMID- 28411660
TI - [The clinical manifestation of suicide and its process].
AB - There emerges from the suicidal process much more than a model. When suicide
forces itself on people, it is extremely difficult for them to pull themselves
out of its grip. From the psychopathological crisis to the psychosocial crisis,
the process acts like a psychological trauma which requires adapted care.
PMID- 28411661
TI - [The suicidal crisis in emergency departments].
AB - Professionals working in emergency departments have an important role to play in
assessing and orienting suicidal patients. A patient's suicide risk must be
assessed using the 'Risk-Emergency-Dangerousness' grid. The main objective of the
initial care is to buy time in order to avoid the patient attempting suicide.
Enabling the patient to return home accompanied by a close friend or family
member after their visit to the emergency department must be favoured whenever
possible, by proposing close monitoring.
PMID- 28411662
TI - [Suicide in adolescence].
AB - On average, in one year in France, six in every thirty teenagers have suicidal
thoughts and two attempt suicide. At this age, suicidal behaviour is structured
around psychopathological, developmental and relational dimensions. Talking about
suicide helps to avoid it but educating teenagers in mental health is the best
way of preventing this definitive act.
PMID- 28411663
TI - [Suicide in the elderly].
AB - Suicide in the elderly is a real public health issue and has been the subject of
a national prevention plan. It is very frequently linked to depression. To
prevent people attempting suicide, health professionals must be trained to
recognise and manage a suicidal crisis.
PMID- 28411664
TI - [Work-related suicide].
AB - Work and the working environment can push a person to suicide, notably in the
context of burnout. There are, however, a wide variety of risk factors, suicide
being multifactorial. Identifying protective elements and recognising the warning
signs is essential.
PMID- 28411665
TI - [The nursing care of a suicidal patient].
AB - The management of a suicidal crisis falls within the scope of nursing care. There
is a high rate of recurrence in the months following an attempted suicide. The
nurse monitoring strategy, based on the principle of the 'recontacting' of
patients, has been tested by the team of a post-emergency psychiatric unit of a
university hospital.
PMID- 28411666
TI - [Psychological support for people bereaved by suicide].
AB - For several years, the Deux-Sevres department has been providing psychological
support to people bereaved after the suicide of a loved one. The care provision
is collaborative and coordinated.
PMID- 28411667
TI - ?
PMID- 28411669
TI - [Acting with compassion, designing care together].
AB - Making care and compassion a central concern in the hospital, and more widely
within the community, is essential. This means reflecting on the existential
questioning imposed by illness, on the key role of the nursing function and the
need to act with compassion, as well as on the awareness of our common
vulnerability and the need to support it.
PMID- 28411668
TI - [Realist evaluation for implementation research].
AB - The realist approach to evaluation can be useful faced with the complexity of
health interventions in populations. Implementation is the process by which these
interventions are put into practice. Scientific realism can provide an important
contribution to the development of programme theories through implementation
research, and help to reveal the distal and proximal mechanisms of programmes
aimed at combatting social inequalities in healthcare.
PMID- 28411670
TI - ?
PMID- 28411671
TI - Evidence to Support Screening Women in Their 40s.
AB - A large body of evidence demonstrates a 30% to 50% mortality benefit of screening
mammography for women aged 40 to 49. Because of more rapid cancer growth rates in
younger women, annual screening is more effective than biennial. Studies indicate
that selective screening of women aged 40 to 49 would miss the majority of breast
cancers. If implemented, recent US Preventive Services Task Force breast cancer
screening guidelines, which recommend against routine screening of women in their
40s, could result in thousands of preventable breast cancer deaths per year.
Vigilance is needed to safeguard younger women's access to screening mammography.
PMID- 28411672
TI - Evidence to Support Screening Women Annually.
AB - The American College of Radiology, American Cancer Society, and US Preventive
Services Task Force agree that mammography screening beginning at age 40 saves
more lives than any other strategy. Despite these seemingly concordant summaries
of the benefits of screening mammography, there are persistent debates regarding
when to start and how often women should participate. Costs of screening, both
monetary and personal, comprise the foundation of arguments against screening.
This article specifically explores the evidence related to screening intervals
and attempts to answer the question: should women be screened annually or
biennially?
PMID- 28411673
TI - Breast Cancer Risk Assessment Models and High-Risk Screening.
AB - It is important to recognize that patients at high risk for breast cancer may
benefit by following breast cancer screening paradigms that are more robust than
those recommended for the average-risk population. Assessing individual cancer
risk and using guidelines to determine if a patient is a candidate for genetic
counseling and possibly genetic testing are essential components to comprehensive
breast cancer screening.
PMID- 28411674
TI - Breast Tomosynthesis: Clinical Evidence.
AB - In the last 20 years, there has been rapid evolution of the clinical research on
digital breast tomosynthesis supporting its adoption in clinical breast imaging
practice. Beginning with proof of principle pilot observational studies and
culminating in prospective population-based screening trials and outcome
reporting from clinical practice, there is a wealth of data on the DBT
technology. This article catalogs the scientific and clinical evidence of DBT,
highlighting some of the most important studies that have been reported to date.
PMID- 28411675
TI - Breast Tomosynthesis: Practical Considerations.
AB - Digital breast tomosynthesis (DBT) is rapidly becoming the new standard of care
for breast cancer screening. DBT has improved on the limitations of traditional
digital mammography by increasing cancer detection and decreasing false-positive
examinations. Interpretation of DBT is slightly different than digital
mammography and therefore experience with the technology is paramount to achieve
best performance. Examples of malignancies that should be recalled and benign
findings that are safely called as benign are provided in this article.
Additionally, practical interpretation methods and implementation protocols are
explained.
PMID- 28411676
TI - Synthesized Digital Mammography Imaging.
AB - Synthesized mammography (SM) is a new imaging technique similar to digital
mammography constructed from an acquired digital breast tomosynthesis (DBT)
examination. SM allows for widespread screening using DBT, maintaining the
benefits of DBT while decreasing the radiation of DBT by nearly half. This
article reviews studies evaluating SM, most of which suggest that SM may be
appropriate to use clinically to replace an actual acquired conventional 2
dimensional full-field digital mammogram (FFDM) when using DBT for breast cancer
screening. These results should be interpreted with caution because there are
inherent differences between SM and FFDM image quality and lesion visibility and
larger, more robust studies still need to be performed.
PMID- 28411677
TI - Breast Density Legislation and Clinical Evidence.
AB - Breast density inform legislation is widely accepted in the United States and has
fueled research regarding the clinical significance of dense breast tissue
present on mammography and the value of supplemental screening. This article
reviews the origins and current status of breast density inform laws and
strategies for optimal breast density determination. Clinical evidence that dense
breast tissue is associated with increased breast cancer risk is presented,
together with a review of relative risk compared with other risk factors.
Finally, there is in-depth analysis regarding the rationale, benefits, and risks
of supplemental screening modalities, including ultrasound, tomosynthesis, and
MRI.
PMID- 28411678
TI - Implementation of Whole-Breast Screening Ultrasonography.
AB - Whole-breast screening ultrasonography is being increasingly implemented in
breast imaging centers because numerous studies have shown the benefit of
supplemental screening for women with dense breasts and breast density
notification laws are becoming more widespread. This article reviews the numerous
considerations involved in integrating a screening ultrasonography program into a
busy practice.
PMID- 28411679
TI - Breast MR Imaging in Newly Diagnosed Breast Cancer.
AB - The role of breast MR imaging in preoperative evaluation of disease extent
remains controversial. MR imaging increases detection of mammographically occult
ipsilateral and contralateral disease, but the clinical impact of these
incidental cancers in unknown. There are no randomized trials of recurrence or
mortality as the primary end point. This missing evidence is needed before the
role of extent of disease MR imaging can be outlined. There are specific clinical
scenarios in which breast MR imaging plays a clear role. In most cases, the
decision to obtain MR imaging depends on physician practice style and patient
preference.
PMID- 28411680
TI - MR Imaging: Future Imaging Techniques.
AB - Breast MR imaging is the most sensitive modality for breast cancer detection.
This high sensitivity has led to widespread adoption of this technique,
particularly in screening women at elevated risk for breast cancer. Despite its
high sensitivity, standard breast MR imaging protocols are limited by moderate
specificity and relative higher cost, longer examination time, longer
interpretation time, and lower availability compared with mammography and
ultrasound. As such, new techniques in MR imaging, including abbreviated breast
MR imaging, pharmacokinetic modeling, and diffusion-weighted imaging, are active
areas of research. This article discusses the rationale, current evidence, and
limitations of these new MR imaging techniques.
PMID- 28411681
TI - Breast PET/MR Imaging.
AB - Breast and whole-body PET/MR imaging is being used to detect local and metastatic
disease and is being investigated for potential imaging biomarkers, which may
eventually help personalize treatments and prognoses. This article provides an
overview of breast and whole-body PET/MR exam techniques, summarizes PET and MR
breast imaging for lesion detection, outlines investigations into multi
parametric breast PET/MR, looks at breast PET/MR in the setting of neo-adjuvant
chemotherapy, and reviews the pros and cons of whole-body PET/MR in the setting
of metastatic or suspected metastatic breast cancer.
PMID- 28411682
TI - Update on Preoperative Breast Localization.
AB - The radiologist plays an important role in detection, diagnosis, localization,
pathologic correlation, and follow-up imaging of breast cancer. A successful
breast surgical treatment program relies on the image guidance tools and skills
of the radiologist and surgeon. This article reviews the evolving tools available
for preoperative localization. Non-wire devices provide a safe, efficient,
noninferior alternative to wire localization and can be placed 0 to 30 days
before scheduled surgery. This technology may evolve to other longer-term,
efficient, and cost-effective applications for patients who require neoadjuvant
treatment or who have findings visible only at MR imaging.
PMID- 28411683
TI - Breast Imaging.
PMID- 28411684
TI - In vivo antimalarial activity of synthetic hepcidin against Plasmodium berghei in
mice.
AB - The present study was designed to investigate the antimalarial activity of
synthetic hepcidin and its effect on cytokine secretion in mice infected with
Plasmodium berghei. The mice were infected with P. berghei intravenously and
treated with hepcidin according to 4-day suppression test and Rane's test. The
serum levels of interleukins (IL-1beta, IL-2, IL-6, IL-10, IL-12p70, and IL-17A),
tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in the
experimental mice were determined using a cytometric bead array (CBA) kit. The
survival rate of the infected mice was also registered. Additionally, the serum
iron, alanine transaminase (ALT), aspartate transaminase (AST), and total
bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted
direct anti-malarial function in vivo and increased survival rate in a dose
dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2,
and Th17 cytokines, TNF-alpha, and IFN-gamma were inhibited by hepcidin. In
conclusion, our results demonstrated that synthetic hepcidin exerts in vivo
antimalarial activity and possesses anti-inflammatory function, which provides a
basis for future design of new derivatives with ideal anti-malarial activity.
PMID- 28411685
TI - Antihyperglycemic, antihyperlipidemic and antioxidant effects of standard ethanol
extract of Bombax ceiba leaves in high-fat-diet- and streptozotocin-induced Type
2 diabetic rats.
AB - The present study aimed at exploring the therapeutic potential of standard
extract of Bombax ceiba L. leaves (BCE) in type 2 diabetic mellitus (T2DM). Oral
administration of BCE at doses of 70, 140, and 280 mg.kg-1, to the normal rats
and the high-fat-diet- and streptozotocin-induced T2DM rats were carried out.
Effects of BCE on blood glucose, body weight, and a range of serum biochemical
parameters were tested, and histopathological observation of pancreatic tissues
was also performed. HPLC-ESI-Q/TOF-MS/MS analysis indicated that the chemical
composition of BCE mainly contained mangiferin, isoorientin, vitexin,
isomangiferin, isovitexin, quercetin hexoside, 2'-trans-O-cumaroyl mangiferin,
and nigricanside. BCE caused a significant decrease in the concentrations of
fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride,
low density lipoprotein-cholesterol, serum insulin, and malondialdehyde, and
increases in oral glucose tolerance, high density lipoprotein-cholesterol, and
superoxide dismutase in the T2DM model rats. Moreover, considerable pancreatic
beta-cells protection effect and stimulation of insulin secretion from the
remaining pancreatic beta-cells could be observed after BCE treatment. The
results indicated that BCE exhibited an excellent hypoglycemic activity, and
alleviated dyslipidemia which is associated with T2DM. Antioxidant activity and
protecting pancreatic beta-cells are the possible mechanisms involved in anti
diabetic activity of BCE.
PMID- 28411686
TI - Mechanism underlying berberine's effects on HSP70/TNFalpha under heat stress:
Correlation with the TATA boxes.
AB - Heat stress can stimulate an increase in body temperature, which is correlated
with increased expression of heat shock protein 70 (HSP70) and tumor necrosis
factor alpha (TNFalpha). The exact mechanism underlying the HSP70 and TNFalpha
induction is unclear. Berberine (BBR) can significantly inhibit the temperature
rise caused by heat stress, but the mechanism responsible for the BBR effect on
HSP70 and TNFalpha signaling has not been investigated. The aim of the present
study was to explore the relationship between the expression of HSP70 and
TNFalpha and the effects of BBR under heat conditions, using in vivo and in vitro
models. The expression levels of HSP70 and TNFalpha were determined using RT-PCR
and Western blotting analyses. The results showed that the levels of HSP70 and
TNFalpha were up-regulated under heat conditions (40 degrees C). HSP70 acted as
a chaperone to maintain TNFalpha homeostasis with rising the temperature, but
knockdown of HSP70 could not down-regulate the level of TNFalpha. Furthermore,
TNFalpha could not influence the expression of HSP70 under normal and heat
conditions. BBR targeted both HSP70 and TNFalpha by suppressing their gene
transcription, thereby decreasing body temperature under heat conditions. In
conclusion, BBR has a potential to be developed as a therapeutic strategy for
suppressing the thermal effects in hot environments.
PMID- 28411687
TI - Oral administration of red ginseng powder fermented with probiotic alleviates the
severity of dextran-sulfate sodium-induced colitis in a mouse model.
AB - Red ginseng is a well-known alternative medicine with anti-inflammatory activity.
It exerts pharmacological effects through the transformation of saponin into
metabolites by intestinal microbiota. Given that intestinal microflora vary among
individuals, the pharmacological effects of red ginseng likely vary among
individuals. In order to produce homogeneously effective red ginseng, we prepared
probiotic-fermented red ginseng and evaluated its activity using a dextran
sulfate sodium (DSS)-induced colitis model in mice. Initial analysis of
intestinal damage indicated that the administration of probiotic-fermented red
ginseng significantly decreased the severity of colitis, compared with the
control and the activity was higher than that induced by oral administration of
ginseng powder or probiotics only. Subsequent analysis of the levels of serum IL
6 and TNF-alpha, inflammatory biomarkers that are increased at the initiation
stage of colitis, were significantly decreased in probiotic-fermented red ginseng
treated groups in comparison to the control group. The levels of inflammatory
cytokines and mRNAs for inflammatory factors in colorectal tissues were also
significantly decreased in probiotic-fermented red ginseng-treated groups.
Collectively, oral administration of probiotic-fermented red ginseng reduced the
severity of colitis in a mouse model, suggesting that it can be used as a
uniformly effective red ginseng product.
PMID- 28411688
TI - Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in
rats.
AB - The present investigation was carried out to evaluate anti-inflammatory and
membrane stabilizing properties of methyl jasmonate (MJ) in experimental rat
models of acute and chronic inflammation. The effects of MJ on acute inflammation
were assessed using carrageenan-induced rat's paw edema model. The granuloma air
pouch model was employed to evaluate the effects of MJ on chronic inflammation
produced by carrageenan in rats. The number of white blood cells (WBC) in pouch
exudates was estimated using light microscopy. The levels of biomarkers of
oxidative stress, such as malondialdehyde (MDA), glutathione (GSH) and activity
of antioxidant enzymes in the exudates, were determined using spectrophotometry.
The membrane stabilizing property of MJ was assessed based on inhibition of
hemolysis of rat red blood cells (RBC) exposed to hypotonic medium. Our results
indicated that MJ (25-100 mg.kg-1, i.p.) produced significant anti-inflammatory
activity in carrageenan-induced paw edema in rats (P < 0.05). MJ reduced the
volume of pouch exudates and the number of WBC in carrageenan-induced
granulomatous inflammation. It also exhibited potent antioxidant and membrane
stabilizing activities. In conclusion, these findings suggest the therapeutic
potentials of methyl jasmonate in disease conditions associated with inflammation
and its anti-inflammatory activity may be related to its antioxidant and membrane
stabilizing activities.
PMID- 28411689
TI - Moutan Cortex and Paeoniae Radix Rubra reverse high-fat-diet-induced metabolic
disorder and restore gut microbiota homeostasis.
AB - The present study was designed to investigate the therapeutic effcts of Moutan
Cortex (CM, root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra (PR,
root of Paeonia veitchii Lynch) on metabolic disorders, focusing on the infuence
of CM and PR on the obesity-related gut microbiota homeostasis. The diet-induced
obese (DIO) mouse model was used to test the therapeutic effects of CM and PR.
The mice were orally administered with CM and PR for 6 weeks, and oral glucose
tolerance test (OGTT) and insulin tolerance test (ITT) were performed to evaluate
the insulin sensitivity of the mice. Sterol-regulatory element binding proteins
(SREBPs) and their target genes were measured by quantitative RT-PCR. High
throughput 16S ribosomal RNA (16S rRNA) gene sequencing technology was used to
determine the composition of gut microbiota, and the metabolites in serum were
analyzed by GC-MS. Our results indicated that CM and PR combination alleviated
obese and insulin resistance in the DIO mice, leading to increased glucose uptake
and gene expression in muscle and liver, and down-regulated SREBPs and their
target genes in liver. Interesting, neither the CM-PR extracts, nor the major
components of CM and PR did not affect SREBPs activity in cultured cells.
Meanwhile, CM and PR significantly modulated the gut microbiota of the high-fat
diet (HFD) treated mice, similar to metformin, and CM-PR reversed the overall
microbiota composition similar to the normal chow diet (NCD) treated mice. In
conclusion, our results provide novel mechanisms of action for the effects of CM
and PR in treating DIO-induced dysregulation of sugar and lipid metabolism.
PMID- 28411690
TI - Two new steroidal saponins isolated from Anemarrhena asphodeloides.
AB - Two new steroidal saponins, named timosaponin P (1) and timosaponin Q (2), were
isolated from the rhizome parts of Anemarrhena asphodeloides Bunge using various
chromatographic methods. Their structures and absolute configurations were
elucidated by a combination of spectroscopic and spectrometric data, including
1D, 2D NMR, HR-ESI-MS and ECD calculations, and this is the first time the
absolute configuration of C-23 of steroidal saponin was confirmed by ECD
calculations.
PMID- 28411691
TI - Flavonoids isolated from Sinopodophylli Fructus and their bioactivities against
human breast cancer cells.
AB - Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a
flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known
compounds (compounds 5-12 and 14-24) were isolated from the fruits of
Sinopodophyllum hexandrum. The structures of new compounds were elucidated by
extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1
6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer
T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11
showed significant cytotoxicity (IC50 values < 10 MUmol.L-1) against T47D cells.
PMID- 28411692
TI - Quantitation of camellianin A in HepG2 cells using a high performance liquid
chromatography-electrospray ionization tandem mass spectrometric method.
AB - The present study was designed to develop a sensitive and selective high
performance liquid chromatography-tandem mass spectrometric method for the
determination of Camellianin A in HepG2 cells. The extraction of Camellianin A
was achieved using 15% trichloroacetic acid and then separated on a C18 column
interfaced with a triple quadrupole tandem mass spectrometer in multiple reaction
monitoring mode. The mobile phase was consisted of methanol-water (0.1% formic
acid) (55 : 45, V/V). The total run time was 5.0 min. The method was linear in
the concentration range of 0.25-250.0 ng.mL-1. The lower limit of quantification
was 0.25 ng.mL-1. The intra- and inter-day relative standard deviations of entire
concentration range were less than 9.3%. The proposed HPLC-MS/MS method was
successfully applied to detect the intracellular concentration of Camellianin A
in HepG2 cells.
PMID- 28411693
TI - Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) meeting in
July 2016 on chronic venous disease: An important first step.
PMID- 28411694
TI - Predictors of failure and complications of catheter-directed interventions for
pulmonary embolism.
AB - OBJECTIVE: Catheter-directed interventions (CDIs) are increasingly performed for
acute pulmonary embolism (PE) as they are presumed to provide similar therapeutic
benefits to systemic thrombolysis while decreasing the dose of thrombolytic
required and the associated risks. This study aimed to identify factors
associated with CDI failure and to describe anticipated complications. METHODS:
Consecutive patients who underwent CDI for massive or submassive PE between 2009
and 2015 were identified; outcomes and complications were retrospectively
collected. CDI clinical failure was defined as major bleeding, perioperative
stroke or other major adverse procedure-related event, decompensation for
submassive or persistent shock for massive PE, need for surgical
thromboembolectomy, or in-hospital death. Univariate analysis was used to study
the factors associated with CDI failure. RESULTS: There were 102 patients who
received a CDI during the study period (36 standard catheter thrombolysis, 60
ultrasound assisted, 6 other; age, 59.2 +/- 15.9 years; male, 50 [49.0%]; massive
PE, 14 [13.7%]). Five patients (4.9%) had a major contraindication and 15
patients (14.7%) had a minor contraindication to systemic thrombolysis. The mean
alteplase dose was 28.2 +/- 18.8 mg (range, 0-123 mg; three patients had already
received systemic lysis). CDI failure occurred in 15 patients (14.7%; 7 in
massive PE, 8 in submassive PE). Of these patients, seven had major bleeding
events, whereas eight patients decompensated. Ten (9.8%) patients had minor
bleeding events (four access related). Factors associated with CDI failure and
major bleeding included massive PE, age >=70 years, and major contraindication to
thrombolytics. Both failures and bleeding events were independent of lysis dose
and CDI technique. CONCLUSIONS: CDIs for acute PE are not risk-free procedures,
and their use should be individualized on the basis of a risk-benefit ratio.
Particularly for patients with major contraindications to systemic thrombolytics,
CDIs should be used selectively. Lytic dose, within the low-volume range
administered in CDI, and type of CDI seem to have no impact on adverse events.
PMID- 28411695
TI - Invited commentary.
PMID- 28411696
TI - First 10-month results of the Vascular Quality Initiative Varicose Vein Registry.
AB - OBJECTIVE: The Vascular Quality Initiative Varicose Vein Registry (VQI VVR)
represents a new Patient Safety Organization database launched in January 2015 as
a collaborative effort between the American Venous Forum and the Society for
Vascular Surgery. This study was undertaken to identify real-world trends among
treatment choices and outcomes of varicose vein patients. METHODS: Registry data
prospectively captured anatomic, procedural, and outcome data for patients with
C2 or more severe disease undergoing intervention for venous varicosities from
January to November 2015. Univariate descriptive statistics of demographic and
procedural data was performed. Preprocedural and postprocedural comparisons were
performed with t-test or chi2 analysis as appropriate. RESULTS: In total, 2661
veins in 1803 limbs of 1406 patients were treated for varicose vein disease. The
majority of patients were female (71.5%) and white (78.3%). Previous varicose
vein treatment had been undertaken by 31.2%. The most common site of reflux was
the great saphenous vein in 74.4%, with 31% of patients having coexisting deep
venous reflux. The right and left extremities were affected equally. Endovenous
treatment of axial reflux was the preferred treatment in 89.1%, divided largely
between radiofrequency ablation (55.2%) and endovenous laser ablation (33.9%).
Clusters were often treated concomitantly with truncal reflux (n = 488 [76%]).
The majority of cluster treatments were performed in an office-based setting
(78.1%). The majority of clusters were located at the calf (89.7%) and treated
with stab phlebectomy (84.8%). For all patients undergoing intervention for
varicose veins, Venous Clinical Severity Score (VCSS) improved on average 4.68 +/
3.35 (n = 719; P < .001) postoperatively from a mean preoperative VCSS of 9.39
+/- 3.87 to a mean postoperative VCSS of 4.71 +/- 3.83. Improvements were seen in
patient-reported outcomes (PROs) of heaviness, achiness, throbbing, swelling,
itching, appearance, and work impact (total score change, 10.75 +/- 6.94; n =
607; P < .001) from a mean preoperative PRO score of 16.48 +/- 6.23 to a mean
postoperative PRO score of 5.73 +/- 5.80. CONCLUSIONS: The VQI VVR provides
detailed assessment of varicose vein interventions and is useful for monitoring
of changes after treatment. Modern-day varicose vein surgery is characterized by
predominantly endovenous treatment of axial vein reflux, phlebectomy of clusters,
and substantial improvements in both VCSS and PROs.
PMID- 28411698
TI - Invited Commentary.
PMID- 28411697
TI - VeClose trial 12-month outcomes of cyanoacrylate closure versus radiofrequency
ablation for incompetent great saphenous veins.
AB - OBJECTIVE: Endovenous cyanoacrylate closure (CAC) is a new U.S. Food and Drug
Administration-approved therapy for treatment of clinically symptomatic venous
reflux in saphenous veins. The device is indicated for the permanent closure of
lower extremity superficial truncal veins, such as the great saphenous vein
(GSV). Early results from a randomized trial of CAC have been reported
previously. Herein we report 1-year outcomes. METHODS: There were 222 subjects
with symptomatic GSV incompetence randomly assigned to receive either CAC (n =
108) or radiofrequency ablation (RFA; n = 114). After the month 3 visit, subjects
could receive adjunctive therapies aimed at treating visible varicosities and
incompetent tributaries. Vein closure was assessed at day 3 and months 1, 3, 6,
and 12 using duplex ultrasound. Additional study visit assessments included the
Venous Clinical Severity Score; Clinical, Etiology, Anatomy, and Pathophysiology
classification; EuroQol-5 Dimension; and Aberdeen Varicose Vein Questionnaire.
Both time to closure and time to first reopening of the target vein were
evaluated using survival curve analysis. Adverse events were evaluated at each
visit. RESULTS: Of 222 enrolled and randomized subjects, a 12-month follow-up was
obtained for 192 (95 CAC and 97 RFA; total follow-up rate, 192/222 [86.5%]). By
month 1, 100% of CAC subjects and 87% of RFA subjects demonstrated complete
occlusion of the target vein. By month 12, the complete occlusion rate was nearly
identical in both groups (97.2% in the CAC group and 97.0% in the RFA group).
Twelve-month freedom from recanalization was similar in the CAC and RFA groups,
although there was a trend toward greater freedom from recanalization in the CAC
group (P = .08). Symptoms and quality of life improved equally in both groups.
Most adverse events were mild to moderate and not related to the device or
procedure. CONCLUSIONS: In patients with incompetent GSVs, treatment with both
CAC and RFA results in high occlusion rates. Time to complete occlusion was
faster with CAC, and freedom from reopening was higher after CAC. Quality of life
scores improved equally with both therapies.
PMID- 28411699
TI - Outcomes of a single-center experience with classification and treatment of
endothermal heat-induced thrombosis after endovenous ablation.
AB - OBJECTIVE: Endothermal heat-induced thrombosis (EHIT) is a known complication of
endothermal venous ablation procedures. EHIT can lead to deep vein
thrombosis/pulmonary embolism, which cause significant disability and, rarely,
death. Other studies have evaluated risk factors for EHIT. There is an accepted
grading system for EHIT, but there is no consensus on treatment type, duration,
or follow-up. We retrospectively evaluated all cases of EHIT after radiofrequency
ablation or endovenous laser ablation at our institution during a 7-year period,
focusing on classification, treatment, and outcomes of EHIT. METHODS: The
analysis included all patients aged >18 years who underwent radiofrequency
ablation or endovenous laser ablation at our institution, Spectrum Health
Hospital Vein Solutions (Grand Rapids, Mich), between January 1, 2008, and
December 31, 2014. Electronic medical records were queried retrospectively to
identify patients with EHIT during the study interval by International
Classification of Diseases-Ninth Revision code. Demographic data, including age,
gender, comorbidities (eg, history of deep venous thrombosis, hypercoagulable
state, family history of blood clots, etc), body mass index, Clinical, Etiology,
Anatomy, and Pathophysiology (CEAP) classification, and use of preoperative
anticoagulation were collected for each patient in the registry. Each patient had
a required postoperative duplex ultrasound (US) examination within 1 to 2 weeks
of the procedure. Preoperative and postoperative US imaging data and procedure
specific data were also recorded for each patient. EHIT was graded from 1 to 4 by
review of the US studies. Each patient's treatment course was reviewed for type
of anticoagulation, duration of treatment, follow-up imaging, and outcome.
RESULTS: From 2008 to 2014, 4799 ablations were performed at Spectrum Health
Hospital Vein Center, and EHIT was identified in 70 patients. At presentation,
87% of patients were asymptomatic, 10% reported pain, and 2.9% reported swelling.
Patients with EHIT grades 1 or 2 were treated with daily aspirin, and most of
those with grades 3 or 4 were treated with systemic anticoagulation. Repeat US
imaging was performed at 1 to 2 weeks to evaluate progression. Progression was
not seen in any patients treated with systemic anticoagulation (grades 3-4).
Thrombus progression occurred in two patients with grades 1 or 2 EHIT treated
with aspirin. A bleeding complication occurred in one patient. CONCLUSIONS: EHIT
after endovenous ablation occurred in ~1.5% of patients, which is similar to that
reported in the literature. Our review shows that systemic anticoagulation is
effective in the prevention of progression with a low risk of bleeding
complications. Patients with EHIT grades 1 or 2 can be treated with aspirin alone
with a low risk of progression (3%).
PMID- 28411700
TI - Association between antithrombotic therapy and risk of postoperative
complications among patients undergoing endovenous laser ablation.
AB - BACKGROUND: The aim of the study was to evaluate the clinical results and
postoperative complications, especially recanalization or bleeding complications,
in patients with saphenous varicose veins undergoing endovenous laser ablation
(EVLA) while receiving antithrombotic therapy (ATT). METHODS: This retrospective
cohort study included 1136 Japanese patients undergoing EVLA with a 980-nm diode
laser between January 2012 and November 2015 at our institution. The patients
were divided into two groups: ATT users (ATT group) and nonusers (control group).
The ATT group was further divided into two subgroups according to whether the
patients received antiplatelet or anticoagulant therapy. Clinical outcomes and
postoperative complications among these patients were assessed. RESULTS:
Approximately 20% of the patients undergoing surgery for saphenous varicose veins
at our institution received ATT. Of these, 141 (12.4%) received antiplatelet
therapy and 95 (8.4%) received anticoagulant therapy. Successful occlusion of the
full length of the treated vein was achieved in 99.9% of the patients; there were
no severe perioperative complications. Endovenous heat-induced thrombosis
occurred in 2.4% of patients, whereas postoperative complications developed in
1.2% of patients. One patient experienced recanalization (0.08%). There were no
significant between-group differences in the incidence of recanalization and
postoperative complications on univariate analysis. CONCLUSIONS: The clinical
outcomes and postoperative complications of EVLA in the ATT group were equivalent
to those in the control group, indicating that EVLA can be safely performed in
patients receiving ATT.
PMID- 28411701
TI - Lack of symmetry in the major lower limb veins.
AB - BACKGROUND: Contemporary texts frequently present the venous system of the lower
limb as a prime example of bilateral symmetry. However, overt bilateral asymmetry
may be noted. This study was designed to examine and to quantify the level of
symmetry in the lower extremity veins. METHODS: This prospective cohort study
evaluated major anatomic differences between right and left lower extremity veins
in adult patients. Two hundred patients presenting with signs and symptoms of
chronic venous disease (CVD; class 2-6) and venous reflux on duplex ultrasound
were examined. A second group of 25 healthy volunteers without reflux or
obstruction were used as controls. Those with conditions that could potentially
alter vasculature, including vascular malformation, lower extremity trauma, and
previously documented surgery for venous disease or bypass operations, were
excluded. Only overt changes in the main superficial veins (great saphenous and
small saphenous veins) and deep veins (femoral, popliteal, peroneal, and tibial
veins) of the lower extremities were examined for symmetry. The level of small
saphenous vein termination and thigh extension veins were also included. Location
and extent of hypoplasia or aplasia and venous duplication or triplication were
noted for all venous segments. RESULTS: Of the 100 patients (200 limbs) with CVD
class 2-3 (age, 49 years; range, 21-78 years), the extent of asymmetry in the
superficial system, deep system, and combined was 84%, 86%, and 100%,
respectively. Similarly, of the 100 patients (200 limbs) with CVD class 4-6 (age,
56 years; range, 28-84 years), the level of asymmetry in the superficial system,
deep system, and combined was 83%, 84%, and 100%, respectively. Fifty (100 limbs)
healthy volunteers (age, 46 years; range, 18-74 years) also presented similarly
elevated levels of asymmetry compared with both cohorts of differing CVD class
severity (superficial, 78%; deep, 84%; both, 100%). The most common reason for
asymmetry in the great saphenous vein was hypoplasia or aplasia, whereas
duplication was rare. In the small saphenous vein, the level of termination,
thigh extension, and hypoplasia were the more frequent reasons. In the deep
veins, duplication of the femoral and popliteal veins at different locations and
extents was the most common finding for asymmetry. These findings remained
consistent for all subgroups of patients and healthy controls. CONCLUSIONS: A
complete lack of symmetry is consistently seen in CVD patients and healthy
subjects. Asymmetry in the veins of the lower extremities appears to be the norm.
This is true despite examination of only overt changes and exclusion of multiple
veins from the comparison.
PMID- 28411702
TI - Outcomes of iliac vein stents after pregnancy.
AB - OBJECTIVE: Stenting is the first-line treatment for obstructive iliocaval lesions
when intervention is required. The aim of the study was to evaluate iliocaval
stent patency during and after pregnancy in women of reproductive age who became
pregnant after stent placement. METHODS: Female patients of reproductive age (18
45 years old) who underwent iliocaval stenting between May 2007 and March 2014
were identified from a three-center prospectively maintained database. Medical
records were reviewed for demographics, baseline risk factors, operative data,
and clinical follow-up to identify pregnancy and postpartum stent imaging. The
primary end point was stent patency. Standard descriptive statistics were used.
RESULTS: There were 310 women of reproductive age who received iliocaval
stenting; 12 were identified to have had at least one pregnancy after stenting.
The mean age was 28 +/- 5 years. One patient received thrombolysis and stenting
at 14 weeks of pregnancy for deep venous thrombosis (DVT) and May-Thurner
syndrome, three for a previous postpartum DVT (2, 4, and 6 weeks postpartum),
three for DVT before any pregnancy with a history of factor V Leiden, and the
remaining five for unprovoked DVT. All stents were self-expanding with a diameter
range of 14 to 16 mm. Mean time from stenting to pregnancy was 23.3 +/- 28
months. All patients had patent stents during pregnancy and were prescribed
therapeutic low-molecular-weight heparin by their obstetrician. One had
asymptomatic left-sided stent compression 1 year after her second delivery,
treated with balloon dilation. At average follow-up of 61 +/- 56 months, all
patients had patent stents with no ultrasound-identified structural damage or
thrombosis. CONCLUSIONS: Pregnancy does not negatively affect the outcomes of
iliocaval stents after lysis of DVT or May-Thurner syndrome. Iliocaval stenting
is not contraindicated in women of reproductive age, although close clinical and
ultrasound follow-up is warranted during and after pregnancy.
PMID- 28411703
TI - A novel duplex finding of superficial epigastric vein flow reversal to diagnose
iliocaval occlusion.
AB - OBJECTIVE: Although duplex ultrasound (DUS) imaging is the current gold standard
in the diagnosis of femoropopliteal deep venous thrombosis, it is not an optimal
diagnostic modality to diagnose iliocaval occlusion. Screening for iliocaval
occlusion thus remains a challenge for clinicians because of the lack of a
reliable noninvasive technique. This challenge results in most patients
undergoing computed tomography venography or magnetic resonance venography or
invasive venography and intravascular ultrasound imaging. This study reports a
novel, yet simple, reproducible and intuitive, surface DUS finding of physiologic
flow reversal within the superficial epigastric vein (SEV) as a sign of proximal
iliocaval occlusion (ICO). METHODS: This was a retrospective study of 15 patients
who were diagnosed with ICO based on the finding of SEV flow reversal on DUS
imaging. Patient demographics, presenting CEAP C scores, ICO characteristics,
correlation with advanced imaging, and short-term follow-up findings are
reported. RESULTS: Physiologic reversal of the SEV resulted in confirmation of
ICO in all patients who underwent advanced imaging, including computed tomography
venography or traditional venogram along with intravascular ultrasound imaging.
All patients who underwent follow-up DUS scans demonstrated normalization of the
SEV flow after ICO recanalization. CONCLUSIONS: ICO can result in deep venous
thrombosis, post-thrombotic syndrome, and chronic venous insufficiency.
Physiologic flow reversal in SEV is diagnostic of ICO. To the best of our
knowledge, this is the first report of this novel DUS finding.
PMID- 28411704
TI - Lymphoscintigraphic abnormalities in the contralateral lower limbs of patients
with unilateral lymphedema.
AB - OBJECTIVE: The contralateral limbs of patients with unilateral lymphedema in the
lower limbs (LLs) can exhibit abnormal lymphatic circulation, even in the absence
of lymphedema. This idea is based on a number of reports that have studied
isolated cases using lymphoscintigraphy. It is likely that these patients
previously had some form of lymphopathy, and the lymphedema arose after the
action of some external factor. However, there are no studies in the literature
that adequately assess the asymptomatic contralateral limbs of these patients or
address the prevalence and characteristics of the abnormal lymphatic circulation
in these limbs. The aim of this study was to assess the prevalence of abnormal
lymphatic circulation in the asymptomatic contralateral limbs of patients with
unilateral lymphedema of the LL. METHODS: Forty-three patients from the angiology
and vascular surgery ward of the Hospital das Clinicas da Universidade Federal de
Pernambuco with unilateral lymphedema of the LL underwent lymphoscintigraphy. All
patients received a subcutaneous injection of 0.2 mL (74 MBq) of a solution of
dextran 70 labeled with technetium Tc 99m in the first interdigital space of each
foot. Images were obtained on two occasions: 10 minutes and 1 hour after the
injection. The study design was transversal prospective. RESULTS: Among the 43
asymptomatic LLs, 30 (70%) showed abnormal lymphatic circulation. The
lymphoscintigraphic abnormalities found were the following: reduced visualization
of the lymphatic vessels and lymph nodes during 1 hour (83%), collateral
circulation (30%), visualization of the inguinal and pelvic lymph nodes after at
least 1 hour (30%), visualization of the popliteal lymph nodes (20%), dilation
and lymphatic tortuosity (20%), and dermal backflow (10%). CONCLUSIONS: In this
study,70% of the patients with unilateral lymphedema of the LL had some form of
lymphopathy in the contralateral limb during the lymphoscintigraphic examination.
These findings could favor the early treatment of these patients to prevent the
disease from progressing to its most severe stage.
PMID- 28411705
TI - Mechanochemical ablation causes endothelial and medial damage to the vein wall
resulting in deeper penetration of sclerosant compared with sclerotherapy alone
in extrafascial great saphenous vein using an ex vivo model.
AB - BACKGROUND: Nonthermal, tumescentless devices are the next generation of
minimally invasive devices to treat varicose veins. We aimed to investigate the
effects of mechanochemical ablation (MOCA) using ClariVein (Vascular Insights,
Quincy, Mass) on ex vivo great saphenous vein with histology and
immunofluorescent staining. METHODS: Extrafascial great saphenous veins were
harvested during surgery for varicose veins and were treated ex vivo for 10 to 11
minutes with either liquid sclerotherapy or the use of ClariVein, with and
without 3% sodium tetradecyl sulfate. Veins were sectioned and subjected to
hematoxylin and eosin staining and immunofluorescent staining for endothelial and
smooth muscle cell markers (CD31 and alpha-actin) to assess overall damage and
cell death in the vein wall compared with control sections. RESULTS: Histologic
observations confirmed intimal damage from ClariVein, as has been previously
shown; however, medial damage was also evident, which was not observed in control
or liquid sclerotherapy sections. Immunofluorescent staining in the three
sections studied showed a 42% decrease in CD31 staining and 27% mean reduction in
alpha-actin staining up to a depth of 300 MUm with liquid sclerotherapy. This
cytotoxic effect was significantly enhanced by MOCA with a reduction in CD31
staining just above 60% and a 46% mean decrease in alpha-actin staining noted up
to a depth of 300 MUm. Far greater reductions in staining compared with
sclerotherapy were observed up to a depth of 600 MUm. CONCLUSIONS: MOCA using 3%
sodium tetradecyl sulfate increases the penetration of the sclerosant and its
effect into the vein wall and shows superior rates of tissue destruction compared
with liquid sclerotherapy alone. In this model, it appears not solely to damage
the endothelium but also to shear the medial layer, creating small lesions into
which sclerosant can flow and exert its cytotoxic effect.
PMID- 28411706
TI - Report of the Society for Vascular Surgery and the American Venous Forum on the
July 20, 2016 meeting of the Medicare Evidence Development and Coverage Advisory
Committee panel on lower extremity chronic venous disease.
AB - On July 20, 2016, a Medicare Evidence Development and Coverage Advisory Committee
panel assessed the benefits and risks of currently used lower extremity chronic
venous disease (CVD) treatments and their effects on health outcome of the
American adult population. The main purpose of the meeting was to advise the
Centers for Medicare & Medicaid Services on coverage determination for
interventions used for treatment of CVD. A systematic review of the Agency for
Healthcare Research and Quality was presented, followed by lectures of invited
experts and a public hearing of representatives of professional societies and the
industry. After discussing critical issues, the panel voted for key questions.
This report summarizes the presented evidence to support recommendations of the
Society for Vascular Surgery/American Venous Forum coalition and the
presentations on selected discussion topics. These included important venous
disease evidence gaps that have not been sufficiently addressed, venous disease
treatment disparities and how they may affect the health outcomes of Medicare
beneficiaries, and mechanisms that might be supported by the Centers for Medicare
& Medicaid Services to improve the evidence base to optimize the care of patients
with lower extremity CVD.
PMID- 28411707
TI - The evidence supporting treatment of reflux and obstruction in chronic venous
disease.
AB - On July 20, 2016, a Medicare Evidence Development and Coverage Advisory Committee
panel convened to assess the evidence supporting treatment of chronic venous
disease. Several societies addressed the questions posed to the panel. A
multidisciplinary coalition, representing nine societies of venous specialists,
reviewed the literature and presented a consensus opinion regarding the panel
questions. The purpose of this paper is to present our coalition's consensus
review of the literature and recommendations for chronic venous disease.
PMID- 28411708
TI - Life-threatening pulmonary embolism associated with multiple venous aneurysms.
AB - Popliteal venous aneurysms (PVAs) are often reported as a cause of pulmonary
embolism. Previous reports documented the association between a single PVA and
pulmonary embolism. We experienced a rare case with multiple venous saccular and
fusiform aneurysms resulting in a nearly fatal pulmonary embolism. Surgical
ligation is usually considered the first-line treatment for PVAs. In our patient,
however, we selected inferior vena cava filter implantation and anticoagulant
therapy to avoid the phlegmasia cerulea dolens caused by ligation of multiple
aneurysms in both legs. We report a patient with multiple venous aneurysms,
including PVAs, causing a nearly fatal pulmonary embolism.
PMID- 28411709
TI - Chronic refractory venous ulcer exacerbated by a congenital pelvic arteriovenous
malformation successfully treated by transarterial Onyx embolization.
AB - Congenital arteriovenous malformations (AVMs) are an important but often
neglected cause of lower extremity venous hypertension. A case of a chronic
refractory venous stasis ulcer of the lower extremity exacerbated by a pelvic AVM
is presented. Healing of the ulcer was achieved at 2 months without recurrence at
1 year after superselective ethylene vinyl alcohol copolymer (Onyx 34; ev3,
Covidien, Plymouth, Minn) embolization of the AVM nidus. Chronic venous
arterialization should be considered in cases of refractory, nonhealing venous
ulcers. Embolotherapy in addition to standard of care therapy can be a
therapeutic measure. Modification of the Clinical, Etiology, Anatomy, and
Pathophysiology (CEAP) classification to include AVMs as a contributing
pathophysiologic process is suggested.
PMID- 28411710
TI - Invited commentary.
PMID- 28411711
TI - An update on the currently available nonthermal ablative options in the
management of superficial venous disease.
AB - BACKGROUND: Chronic venous insufficiency affects millions of Americans with
symptoms spanning a broad range. Saphenous incompetence resulting in chronic
reflux is at the root of most disease and is amenable to surgical correction.
METHODS: We conducted a systematic review of the literature on nonthermal
ablative techniques using a MEDLINE (Ovid) search from January 2000 to August
2016. Only prospective studies and literature review articles in the English
language were included for final analysis. RESULTS: A total of 358 unique
articles were identified, with a total of 60 articles meeting the stated
inclusion and exclusion criteria. Historically, nonthermal ablative techniques
have not demonstrated clinical results on par with thermal ablative
interventions. However, three newer nonthermal ablative techniques have become
available for use in the United States. Review of the literature demonstrated
significant improvements in nonthermal ablative results, with intermediate-term
data suggesting improved durability. CONCLUSIONS: Advances in nonthermal ablative
techniques have led to a developing role and acceptance in the primary management
of varicose veins and venous insufficiency, even in the setting of challenging
cases.
PMID- 28411712
TI - Treatment options and outcomes for caval thrombectomy and resection for renal
cell carcinoma.
AB - OBJECTIVE: Advanced renal cell carcinoma (RCC) has a significant predisposition
to vascular invasion. Tumor vascular invasion and thrombus are found in the renal
vein and the inferior vena cava (IVC) in up to 10% to 25% of patients. This study
reviewed the current status of radical nephrectomy with IVC thrombectomy for
advanced RCC. METHODS: A two-level search strategy of the literature (MEDLINE,
PubMed, The Cochrane Library, and Google Scholar) for relevant articles listed
between January 2000 and December 2015 was performed. The review was confined to
patients with primary RCC associated with vascular invasion. RESULTS: Untreated
RCC with intravascular thrombus has a median survival of 5 months. Surgical
exposure and intervention are tailored to the level of tumor thrombus. The 30-day
mortality for radical nephrectomy with IVC thrombectomy is low (1.5%-10%), and
the complication rates have been reported to be 18%, 20%, 26%, and 47% for IVC
tumor thrombus level I, II, III, and IV disease, respectively. Disease-specific
survival ranges from 40% to 60% at 5 years after nephrectomy and removal of the
intravascular tumor. CONCLUSIONS: Radical nephrectomy with IVC thrombectomy is an
effective cancer control operation that can be safely performed with acceptable
mortality and morbidity. Preoperative imaging coupled with perioperative surgical
management of the IVC is critical to procedural success and patient outcomes.
PMID- 28411713
TI - Cosmetic sclerotherapy.
AB - Telangiectasias and spider veins are considered a common cosmetic concern for
both women and men. Sclerotherapy is a frequently used, low-risk, and highly
successful method to treat these venous problems. This article reviews the
pathophysiology and diagnosis of telangiectasias and reticular veins as well as
the currently available agents and techniques of sclerotherapy. The possible
complications and adverse outcomes of sclerotherapy are described. Standard care
and follow-up for patients after the procedure are outlined. Also included are
tips and tricks found to be valuable in a busy vein practice.
PMID- 28411714
TI - Evaluating the venous experience in vascular surgery training.
AB - OBJECTIVE: There is an increasing recognition and treatment of venous disease in
the United States; results of the Society for Vascular Surgery 2014 membership
survey showed that venous disease represents 18.8% of a vascular surgeon's
current practice. Despite this, there are no operative objectives or case
requirements specific to venous disease for vascular surgery trainees. The
objective of this study was to examine the current venous surgical training
experience of graduating vascular surgery trainees. METHODS: Following
Institutional Review Board waiver and Association of Program Directors in
Vascular Surgery and Residency Review Committee approval, results of the 2014
Association of Program Directors in Vascular Surgery Educational Needs Assessment
Survey pertinent to venous training as well as the Vascular Surgery In-Training
Examination (VSITE) venous scores were summarized. Using the Residency Review
Committee case log database, venous case logs of 0/5 resident and 5/2 fellow
vascular surgery graduates from 2012 to 2015 differentiated by Current Procedural
Technology code were summarized. Venous case logs of 0/5 vascular surgery
residents were compared with those of 5/2 fellows using a Student t-test, with
results considered statistically significant at P < .05. RESULTS: Of the recent
vascular surgery graduates, 15% thought they encountered training gaps in venous
procedures; 54% thought this was due to a gap in vascular surgery training,
whereas 43% thought this was due to evolution in technology. Venous VSITE scores
were similar between 0/5 residents and 5/2 fellows (69% vs 76% correct answers,
respectively), as were overall VSITE scores (70% vs 74% correct answers,
respectively). The 0/5 residents completed between 11 and 264 cases and 5/2
fellows completed between 1 and 188 cases during their training. The 0/5
residents' venous cases were 8.1% of overall cases and the 5/2 fellows' cases
were 4.3% of overall cases during their training. CONCLUSIONS: Current vascular
surgery trainee experience is highly variable and not consistent with future
vascular surgery clinical practice. Vascular surgery trainee fund of knowledge
does not appear affected. Program directors should consider developing a better
defined venous curriculum that includes venous case minimums in defined
categories.
PMID- 28411715
TI - Proposal for a national coverage determination for the treatment of varicose
veins and venous disease due to disparate Centers for Medicare and Medicaid
Services local coverage determination policies.
AB - Varicose veins and chronic venous disease are common problems in the United
States. Persons with these conditions often have an adversely affected quality of
life. There are a number of proven interventions to treat varicose veins and to
improve patients' life quality, but these interventions are often restricted by
the Centers for Medicare and Medicaid Services and private third-party payers.
The Centers for Medicare and Medicaid Services have private contractors that
administer Medicare policies in 10 jurisdictions across the United States. There
is no national policy or coverage for the treatment of varicose veins; rather,
there are multiple, disparate regional policies written by the contractors that
cover the same Medicare beneficiary population. These disparate policies are not
evidence based and provide unfair coverage of the same disease to the Medicare
population, depending on where they live. Our proposal is for a national coverage
determination policy for the treatment of varicose veins.
PMID- 28411716
TI - Pathophysiology of varicose veins.
AB - BACKGROUND: Varicose veins, a common problem with effects on quality of life,
account for a significant cost burden on the health care system. Despite their
prevalence, the pathophysiologic mechanism of varicose veins remains incompletely
understood. The fundamental issue is whether venous hypertension and valvular
incompetence precede and influence the development of vein wall changes or
whether the reverse is true. METHODS: We have reviewed the English-language
literature to provide the most current understanding of the hemodynamic and
cellular and molecular processes that underlie the development of varicose veins.
RESULTS: Data at this time remain inconclusive, with compelling arguments to be
made for both sides. It is clear that valvular incompetence and hemodynamic
factors play a significant role, despite heterogeneity in study findings and lack
of clear data for a specific pattern of valvular incompetence as an inciting
factor. Numerous factors influence the development of varices on the cellular
level, including hypoxia, dysregulated apoptosis, and alterations in the
extracellular matrix. CONCLUSIONS: Based on currently available evidence,
varicose veins are a complex disease with multifactorial pathogenesis; it is as
yet not possible to state conclusively what inciting factor is responsible for
the development of varicose veins, and their development may result from
imbalance of any number of several factors.
PMID- 28411717
TI - Utilizing registries to meet Medicare reimbursement requirements.
PMID- 28411718
TI - Regarding "Validation of the novel venous drainage index with stepwise increases
in thigh compression pressure in the quantification of venous obstruction".
PMID- 28411719
TI - Reply.
PMID- 28411720
TI - Inter- and intra- observer reliability of risk assessment of repetitive work
without an explicit method.
AB - A common way to conduct practical risk assessments is to observe a job and report
the observed long term risks for musculoskeletal disorders. The aim of this study
was to evaluate the inter- and intra-observer reliability of ergonomists' risk
assessments without the support of an explicit risk assessment method. Twenty-one
experienced ergonomists assessed the risk level (low, moderate, high risk) of
eight upper body regions, as well as the global risk of 10 video recorded work
tasks. Intra-observer reliability was assessed by having nine of the ergonomists
repeat the procedure at least three weeks after the first assessment. The
ergonomists made their risk assessment based on his/her experience and knowledge.
The statistical parameters of reliability included agreement in %, kappa,
linearly weighted kappa, intraclass correlation and Kendall's coefficient of
concordance. The average inter-observer agreement of the global risk was 53% and
the corresponding weighted kappa (Kw) was 0.32, indicating fair reliability. The
intra-observer agreement was 61% and 0.41 (Kw). This study indicates that risk
assessments of the upper body, without the use of an explicit observational
method, have non-acceptable reliability. It is therefore recommended to use
systematic risk assessment methods to a higher degree.
PMID- 28411721
TI - Ergonomic analysis of construction worker's body postures using wearable mobile
sensors.
AB - Construction jobs are more labor-intensive compared to other industries. As such,
construction workers are often required to exceed their natural physical
capability to cope with the increasing complexity and challenges in this
industry. Over long periods of time, this sustained physical labor causes bodily
injuries to the workers which in turn, conveys huge losses to the industry in
terms of money, time, and productivity. Various safety and health organizations
have established rules and regulations that limit the amount and intensity of
workers' physical movements to mitigate work-related bodily injuries. A precursor
to enforcing and implementing such regulations and improving the ergonomics
conditions on the jobsite is to identify physical risks associated with a
particular task. Manually assessing a field activity to identify the ergonomic
risks is not trivial and often requires extra effort which may render it to be
challenging if not impossible. In this paper, a low-cost ubiquitous approach is
presented and validated which deploys built-in smartphone sensors to
unobtrusively monitor workers' bodily postures and autonomously identify
potential work-related ergonomic risks. Results indicates that measurements of
trunk and shoulder flexions of a worker by smartphone sensory data are very close
to corresponding measurements by observation. The proposed method is applicable
for workers in various occupations who are exposed to WMSDs due to awkward
postures. Examples include, but are not limited to industry laborers, carpenters,
welders, farmers, health assistants, teachers, and office workers.
PMID- 28411722
TI - Kinematic and ergonomic assessment of laparoendoscopic single-site surgical
instruments during simulator training tasks.
AB - While laparoendoscopic single-site surgery (LESS) appears to be feasible and
safe, instrument triangulation, tissue handling, and other bimanual tasks are
difficult even for experienced surgeons. Novel technologies emerged to overcome
LESS' procedural and ergonomic difficulties of "tunnel vision" and "instrument
clashing." Surgeon kinematics, self-reported workload and upper body discomfort
were used to compare straight, bent and two articulating instruments while
performing two basic surgical tasks in a LESS simulator. All instruments resulted
in bilateral elevation and rotation of the shoulders, excessive forearm motion
and flexion and ulnar deviation of wrists. Surgeons' adopted non-neutral upper
extremity postures and performed excessive joint excursions to compensate for
reduced freedom of movement at the single insertion site and to operate the
instrument mechanisms. LESS' cosmetic benefits continue to impact laparoscopic
surgery and by enabling performance through improved instruments, ergonomic
improvement for LESS can reduce negative impact on surgeon well-being and patient
safety.
PMID- 28411723
TI - Fatigue of Chinese railway employees and its influential factors: Structural
equation modelling.
AB - Fatigue is an identifiable and preventable cause of accidents in transport
operations. Regarding the railway sector, incident logs and simulation studies
show that employee fatigue leads to lack of alertness, impaired performance, and
occurrence of incidents. China has one of the largest rail systems in the world,
and Chinese railway employees work under high fatigue risks; therefore, it is
important to assess their fatigue level and find the major factors leading to
fatigue. We designed a questionnaire that uses Multidimensional Fatigue
Instrument (MFI-20), NASA-TLX and subjective rating of work overtime feelings to
assess employee fatigue. The contribution of each influential factor of fatigue
was analysed using structural equation modelling. In total, 297 employees from
the rail maintenance department and 227 employees from the locomotive department
returned valid responses. The average scores and standard deviations for the five
subscales of MFI-20, namely General Fatigue, Physical Fatigue, Reduced Activity,
Reduced Motivation, and Mental Fatigue, were 2.9 (0.8), 2.8 (0.8), 2.5 (0.8), 2.5
(0.7), and 2.4 (0.8) among the rail maintenance employees and 3.5 (0.8), 3.5
(0.7), 3.3 (0.7), 3.0 (0.6), and 3.1 (0.7), respectively, among the locomotive
employees. The fatigue of the locomotive employees was influenced by feelings
related to working overtime (standardized r = 0.22) and workload (standardized r
= 0.27). The work overtime control and physical working environment significantly
influenced subjective feelings (standardized r = -0.25 and 0.47, respectively),
while improper work/rest rhythms and an adverse physical working environment
significantly increased the workload (standardized r = 0.48 and 0.33,
respectively).
PMID- 28411724
TI - Thermal comfort of seats as visualized by infrared thermography.
AB - Published studies that deal with the question of how the temperature of chair
seats influences human activities are few, but the studies considering such a
factor, a function of the type of material, could contribute to improvements in
the design of chairs. This study evaluates seat temperatures of 8 types of chairs
made of different materials. The parts of the furniture that people come into
contact with, and the thermal response of the material to heating and cooling
have been evaluated. Infrared thermography was used for this, as it is a non
contact technique that does not present any type of risk in the measurement of
temperatures. Seats made of synthetic leather (leatherette), wood and polyester
fabric were found to have the highest temperatures, and the plywood seat showed
the lowest. The study has also revealed that thermography can contribute to
studies of thermal comfort of chair seats in addition to determining the most
suitable material.
PMID- 28411725
TI - Effects of heat stress on risk perceptions and risk taking.
AB - Exposure to extreme heat at work is a serious occupational hazard, as exposure
can result in heat-related illnesses, and it has been linked to increased risk of
accidents and injuries. The current study aimed to examine whether heat exposure
is related to changes in individuals' psychological process of risk evaluation,
and whether acclimatization can mitigate the effect of heat exposure. A study
with quasi-experiment research design was used to compare participants' risk
perceptions and risk-taking behaviors at baseline, initial exposure to heat, and
exposure after acclimatization across male participants who were exposed to heat
(N = 6), and males (N = 5) and females (N = 6) who were in the control group who
were exposed to ambient temperature. Results show that participants perceived the
same risky behaviors to be less risky (p = 0.003) and demonstrated increased risk
taking behaviors (p = 0.001) after initial heat exposure. While their risk
perceptions returned to baseline level after acclimatization, their risk-taking
behaviors remained heightened (p = 0.031). Participants who were not exposed to
heat showed no significant fluctuation in their risk perceptions and risk-taking.
Our findings support that risk-related processes may explain the effects of heat
exposure on increased accidents and injuries beyond its direct impact on heat
related illnesses.
PMID- 28411726
TI - A wellness platform for stereoscopic 3D video systems using EEG-based visual
discomfort evaluation technology.
AB - Recent advances in three-dimensional (3D) video technology have extended the
range of our experience while providing various 3D applications to our everyday
life. Nevertheless, the so-called visual discomfort (VD) problem inevitably
degrades the quality of experience in stereoscopic 3D (S3D) displays. Meanwhile,
electroencephalography (EEG) has been regarded as one of the most promising brain
imaging modalities in the field of cognitive neuroscience. In an effort to
facilitate comfort with S3D displays, we propose a new wellness platform using
EEG. We first reveal features in EEG signals that are applicable to practical S3D
video systems as an index for VD perception. We then develop a framework that can
automatically determine severe perception of VD based on the EEG features during
S3D video viewing by capitalizing on machine-learning-based braincomputer
interface technology. The proposed platform can cooperate with advanced S3D video
systems whose stereo baseline is adjustable. Thus, the optimal S3D content can be
reconstructed according to a viewer's sensation of VD. Applications of the
proposed platform to various S3D industries are suggested, and further technical
challenges are discussed for follow-up research.
PMID- 28411727
TI - Evaluation of the Indonesian National Standard for elementary school furniture
based on children's anthropometry.
AB - In Indonesia, National Standardization Agency of Indonesia issued the Indonesian
National Standard SNI 12-1015-1989 and SNI 12-1016-1989 to define the type of
furniture dimensions that should be used by children in the elementary school
level. This study aims to examine whether the current national standards for
elementary school furniture dimensions issued by National Standardization Agency
of Indonesia match the up-to-date Indonesian children's anthropometry. Two types
of school furniture, small type (Type I, for grade 1-3) and large type (Type II,
for grade 4-6), were evaluated in terms of seat height, seat depth, seat width
and backrest height of a chair as well as the height and underneath height of a
desk. 1146 students aged between 6 and 12 years old participated in the study.
Seven anthropometric measurements were taken including stature, sitting shoulder
height, sitting elbow height, popliteal height, buttock-popliteal length, knee
height and hip breadth. Based on the standard school furniture dimensions and
students' body dimensions, numbers of matches and mismatches between them were
computed. Results indicated a substantial degree of mismatch between children's
anthropometry and the standard dimensions of school furniture. The standard seat
height was not appropriate for students among different grades with the mismatch
percentage ranging from 63.4% to 96.7% for Type I and 72.7% to 99.0% for Type II.
For desk height, the standard dimensions were not appropriate for students among
different grades with the mismatch percentage ranging from 32.3% to 88.9% for
Type I and 67.7% to 99.0% for Type II. Apparently, the current standards are out
of date and need to be updated. Four different sizes of school furniture were
hence proposed to accommodate the variation in students' anthropometry from Grade
1 to Grade 6. The proposed standard dimensions (PrS) of school furniture cover a
slightly broader range of age and present a higher cumulative fit than the
current standard dimensions (CrS). In addition, a better strategy for sizing can
be also developed to fit chairs and desks to a larger number of students.
PMID- 28411728
TI - Improvements in musculoskeletal health and computing behaviors: Effects of a
macroergonomics office workplace and training intervention.
AB - Computer use and its association with musculoskeletal and visual symptoms is an
escalating concern. Organizations are shifting to a more proactive injury
prevention perspective. Accordingly, a macroergonomics intervention consisting of
flexible workplace design and office ergonomics training was designed to examine
the effects on worker's computing behaviors, postures, and musculoskeletal
discomfort, and their relationship to psychosocial factors. Participants were
assigned to either group: 1) no-intervention control 2) flexible Workplace-only
(WP-only), and 3) flexible Workplace + Training (WP+T). Observational findings
indicate both intervention groups experienced positive, significant changes in
improved workstation arrangements and computing postures, with the WP+T
intervention group exhibiting a higher, significant change of behavioral
translation. Also, significant, positive relationships between observed postures
and musculoskeletal discomfort/pain were found. The intervention effect was
stronger when management was responsive to workers' ergonomics needs. This study
suggests that a macroergonomics intervention can produce beneficial effects for
office and computer workers and organizations.
PMID- 28411729
TI - Design with limited anthropometric data: A method of interpreting sums of
percentiles in anthropometric design.
AB - Occasionally practitioners must work with single dimensions defined as
combinations (sums or differences) of percentile values, but lack information
(e.g. variances) to estimate the accommodation achieved. This paper describes
methods to predict accommodation proportions for such combinations of percentile
values, e.g. two 90th percentile values. Kreifeldt and Nah z-score multipliers
were used to estimate the proportions accommodated by combinations of percentile
values of 2-15 variables; two simplified versions required less information about
variance and/or correlation. The estimates were compared to actual observed
proportions; for combinations of 2-15 percentile values the average absolute
differences ranged between 0.5 and 1.5 percentage points. The multipliers were
also used to estimate adjusted percentile values, that, when combined, estimate a
desired proportion of the combined measurements. For combinations of two and
three adjusted variables, the average absolute difference between predicted and
observed proportions ranged between 0.5 and 3.0 percentage points.
PMID- 28411730
TI - Thermal sensation, rate of temperature change, and the heat dissipation design
for tablet computers.
AB - Past research has shown that the rate of change of skin surface temperature can
affect thermal sensation. This study investigated users' thermal responses to a
tablet heating surface with different heat pads and different temperature change
rates. The test conditions included: A. keeping the surface at a constant 42
degrees C, B. increasing the surface temperature from 38 degrees C to 42
degrees C at a rate of 0.02 degrees C/s in progressive intervals, C. increasing
the temperature at 0.15 degrees C/s in progressive intervals, and D. Heating two
left and right side pads alternately from 38 degrees C to 42 degrees C at 0.15
degrees C/s in progressive intervals. Overall results showed the lowest
temperature change rate of 0.02 degrees C/s was most preferred in terms of
thermal comfort. The findings suggest a potential to improve user thermal
experience by dissipating tablet computer heat at a lower temperature change
rate, or by alternating the dissipation areas.
PMID- 28411731
TI - Take-over again: Investigating multimodal and directional TORs to get the driver
back into the loop.
AB - When a highly automated car reaches its operational limits, it needs to provide a
take-over request (TOR) in order for the driver to resume control. The aim of
this simulator-based study was to investigate the effects of TOR modality and
left/right directionality on drivers' steering behaviour when facing a head-on
collision without having received specific instructions regarding the directional
nature of the TORs. Twenty-four participants drove three sessions in a highly
automated car, each session with a different TOR modality (auditory,
vibrotactile, and auditory-vibrotactile). Six TORs were provided per session,
warning the participants about a stationary vehicle that had to be avoided by
changing lane left or right. Two TORs were issued from the left, two from the
right, and two from both the left and the right (i.e., nondirectional). The
auditory stimuli were presented via speakers in the simulator (left, right, or
both), and the vibrotactile stimuli via a tactile seat (with tactors activated at
the left side, right side, or both). The results showed that the multimodal TORs
yielded statistically significantly faster steer-touch times than the unimodal
vibrotactile TOR, while no statistically significant differences were observed
for brake times and lane change times. The unimodal auditory TOR yielded
relatively low self-reported usefulness and satisfaction ratings. Almost all
drivers overtook the stationary vehicle on the left regardless of the
directionality of the TOR, and a post-experiment questionnaire revealed that most
participants had not realized that some of the TORs were directional. We conclude
that between the three TOR modalities tested, the multimodal approach is
preferred. Moreover, our results show that directional auditory and vibrotactile
stimuli do not evoke a directional response in uninstructed drivers. More salient
and semantically congruent cues, as well as explicit instructions, may be needed
to guide a driver into a specific direction during a take-over scenario.
PMID- 28411732
TI - Design and validation of an aircraft seat comfort scale using item response
theory.
AB - This article aims to evaluate the psychometric properties of a scale that
measures aircraft seat comfort. Factor analysis was used to study data variances.
Psychometric quality was checked by using Item Response Theory. The sample
consisted of 1500 passengers who completed a questionnaire at a Brazilian
airport. Full information factor analysis showed the presence of one dominant
factor explaining 34% of data variance. The scale generated covered all levels of
comfort data, from 'no comfort' to 'maximum comfort'. The results show that the
passengers consider there is comfort, but this is very minimal when these
passengers have to perform their desired activities. It tends to increase when
aspects of the aircraft seating are improved and positive emotions are elicited.
Comfort peaks when pleasure is experienced and passenger expectations are
exceeded (maximum comfort). This outcome seems consistent with the literature.
Further research is advised to compare the outcome of this questionnaire with
other research methods, and to check if the questionnaire is sensitive enough and
whether its conclusions are useful in practice.
PMID- 28411733
TI - Can an aircraft be piloted via sonification with an acceptable attentional cost?
A comparison of blind and sighted pilots.
AB - In the aeronautics field, some authors have suggested that an aircraft's attitude
sonification could be used by pilots to cope with spatial disorientation
situations. Such a system is currently used by blind pilots to control the
attitude of their aircraft. However, given the suspected higher auditory
attentional capacities of blind people, the possibility for sighted individuals
to use this system remains an open question. For example, its introduction may
overload the auditory channel, which may in turn alter the responsiveness of
pilots to infrequent but critical auditory warnings. In this study, two groups of
pilots (blind versus sighted) performed a simulated flight experiment consisting
of successive aircraft maneuvers, on the sole basis of an aircraft sonification.
Maneuver difficulty was varied while we assessed flight performance along with
subjective and electroencephalographic (EEG) measures of workload. The results
showed that both groups of participants reached target-attitudes with a good
accuracy. However, more complex maneuvers increased subjective workload and
impaired brain responsiveness toward unexpected auditory stimuli as demonstrated
by lower N1 and P3 amplitudes. Despite that the EEG signal showed a clear
reorganization of the brain in the blind participants (higher alpha power), the
brain responsiveness to unexpected auditory stimuli was not significantly
different between the two groups. The results suggest that an auditory display
might provide useful additional information to spatially disoriented pilots with
normal vision. However, its use should be restricted to critical situations and
simple recovery or guidance maneuvers.
PMID- 28411734
TI - HRI usability evaluation of interaction modes for a teleoperated agricultural
robotic sprayer.
AB - Teleoperation of an agricultural robotic system requires effective and efficient
human-robot interaction. This paper investigates the usability of different
interaction modes for agricultural robot teleoperation. Specifically, we examined
the overall influence of two types of output devices (PC screen, head mounted
display), two types of peripheral vision support mechanisms (single view,
multiple views), and two types of control input devices (PC keyboard, PS3
gamepad) on observed and perceived usability of a teleoperated agricultural
sprayer. A modular user interface for teleoperating an agricultural robot sprayer
was constructed and field-tested. Evaluation included eight interaction modes:
the different combinations of the 3 factors. Thirty representative participants
used each interaction mode to navigate the robot along a vineyard and spray grape
clusters based on a 2 * 2 * 2 repeated measures experimental design. Objective
metrics of the effectiveness and efficiency of the human-robot collaboration were
collected. Participants also completed questionnaires related to their user
experience with the system in each interaction mode. Results show that the most
important factor for human-robot interface usability is the number and placement
of views. The type of robot control input device was also a significant factor in
certain dependents, whereas the effect of the screen output type was only
significant on the participants' perceived workload index. Specific
recommendations for mobile field robot teleoperation to improve HRI awareness for
the agricultural spraying task are presented.
PMID- 28411735
TI - A practical review of energy saving technology for ageing populations.
AB - Fuel poverty is a critical issue for a globally ageing population. Longer
heating/cooling requirements combine with declining incomes to create a problem
in need of urgent attention. One solution is to deploy technology to help elderly
users feel informed about their energy use, and empowered to take steps to make
it more cost effective and efficient. This study subjects a broad cross section
of energy monitoring and home automation products to a formal ergonomic analysis.
A high level task analysis was used to guide a product walk through, and a
toolkit approach was used thereafter to drive out further insights. The findings
reveal a number of serious usability issues which prevent these products from
successfully accessing an important target demographic and associated energy
saving and fuel poverty outcomes. Design principles and examples are distilled
from the research to enable practitioners to translate the underlying research
into high quality design-engineering solutions.
PMID- 28411736
TI - Masked priming for the comparative evaluation of camouflage conspicuity.
AB - Human observer test and evaluation of camouflage patterns is critical for
understanding relative pattern conspicuity against a range of background scenes.
However, very few validated methodologies exist for this purpose, and those that
do carry several limitations. Five experiments examined whether masked priming
with a dot probe could be used to reliably differentiate camouflage patterns. In
each experiment, participants were primed with a camouflaged target appearing on
the left or right of the screen, and then made a speeded response to a dot probe
appearing on the same (congruent) or different (incongruent) side. Across
experiments we parametrically varied prime duration between 35, 42, 49, 56, and
63 ms. Results demonstrated that as prime duration increased, a response time
disadvantage for incongruent trials emerged with certain camouflage patterns.
Interestingly, the most conspicuous patterns showed behavioral differences at a
relatively brief (49 ms) prime duration, whereas behavioral differences were only
found at longer prime durations for less conspicuous patterns; this overall
results pattern matched that predicted by a visual salience model. Together, we
demonstrate the viability of masked priming for the test and evaluation of
camouflage patterns, and correlated outcomes for saliency models and primed
object processing.
PMID- 28411737
TI - Neck posture during lifting and its effect on trunk muscle activation and lumbar
spine posture.
AB - Neck and head posture have been found to have a significant influence on the
posture of the lower spine region during lifting and both an extended/upward gaze
and a flexed/downward gaze have been hypothesized to lead to increased pain
and/or overuse of the neck musculature. As a result, strength training
recommendations have turned to the use of a retracted neck posture as being the
safer posture to assume during lifting. This study examined trunk and neck muscle
activity and lumbar spine posture in seven participants while performing moderate
load lifts using a retracted neck posture (chin drawn in posteriorly; recently
gaining popularity among coaches, trainers, and physical therapists to reduce
neck pain during lifting, and freestyle neck posture (no instructions given). The
retracted neck resulted in less lumbar spine flexion and increased lumbar erector
spinae, external oblique, and sternocleidomastoid activity. The retracted posture
also resulted in decreased activity in the thoracic erector spinae and dorsal
neck musculature. The increased trunk and sternocleidomastoid activity and
decreased spine flexion observed in the seven participants of this study when
lifting with a retracted neck may have the potential to help lower the risk of
spine pain/injury.
PMID- 28411738
TI - Implementing powered stretcher and load systems was a cost effective intervention
to reduce the incidence rates of stretcher related injuries in a paramedic
service.
AB - Paramedic services are considering moving towards the use of powered stretcher
and load systems to reduce stretcher related injuries, but cost is perceived as a
barrier. This study compared injury incidence rates, days lost, and compensation
costs between Niagara Emergency Medical Service (NEMS) and Hamilton Paramedic
Service (HPS) pre- (four years) and post- (one year) implementation of powered
stretcher and load systems in NEMS. Prior to the intervention stretcher related
musculoskeletal disorder (MSD) incidence rates averaged 20.0 (+/-6.8) and 17.9
(+/-6.4) per 100 full time equivalent (FTE), in NEMS and HPS respectively. One
year post intervention rates decreased to 4.3 per 100 FTE in NEMS, a 78%
reduction. Rates modestly increased to 24.6 per 100 FTE in HPS in same period.
Cost-benefit analysis estimated that the added cost to purchase powered stretcher
and load systems would be recovered within their expected 7-year service life due
to the reduction in compensation costs.
PMID- 28411739
TI - Qualitative ergonomics/human factors research in health care: Current state and
future directions.
AB - The objective of this systematic review was to understand the current state of
Ergonomics/Human Factors (E/HF) qualitative research in health care and to draw
implications for future efforts. This systematic review identified 98 qualitative
research papers published between January 2005 and August 2015 in the seven
journals endorsed by the International Ergonomics Association with an impact
factor over 1.0. The majority of the studies were conducted in hospitals and
outpatient clinics, were focused on the work of formal health care professionals,
and were classified as cognitive or organizational ergonomics. Interviews, focus
groups, and observations were the most prevalent forms of data collection.
Triangulation and data archiving were the dominant approaches to ensuring rigor.
Few studies employed a formal approach to qualitative inquiry. Significant
opportunities remain to enhance the use of qualitative research to advance
systems thinking within health care.
PMID- 28411740
TI - Optimal bus temperature for thermal comfort during a cool day.
AB - A challenge for electric buses is to minimize heating and cooling power to
maximally extend the driving range, but still provide sufficient thermal comfort
for the driver and passengers. Therefore, we investigated the thermal sensation
(TS) and thermal comfort (TC) of passengers in buses during a cool day
(temperature 13.4 +/- 0.5 degrees C, relative humidity (RH) 60 +/- 5.8%) typical
for the Dutch temperate maritime climate. 28 Males and 72 females rated TS and TC
and gave information on age, stature, body weight and worn garments. The
temperature in the bus of 22.5 +/- 1.1 degrees C and RH of 59.9 +/- 5.8%
corresponded to a slightly warm feeling (TS = 0.85 +/- 1.06) and TC of 0.39 +/-
0.65. TS related significantly to bus temperature, clothing insulation and age.
Linear regression based on these parameters showed that the temperature in the
bus corresponding to TC = 0 and TS = 0 would have been 20.9 +/- 0.6 degrees C.
In conclusion, a 1.6 degrees C lower bus temperature during the investigated
cool day probably would have led to less thermal discomfort and energy savings of
electrical busses. The methodology to relate climatic measurements to subjective
assessments is currently employed in a wider climatic range and may prove to be
useful to find a better balance between thermal comfort and energy savings of the
bus.
PMID- 28411741
TI - Required friction during overground walking is lower among obese compared to non
obese older men, but does not differ with obesity among women.
AB - Obesity and aging have been independently associated with altered required
friction during walking, but it is unclear how these factors interact to
influence the likelihood of slipping. Therefore, the purpose of this study was to
determine whether there are differences related to obesity and aging on required
friction during overground walking. Fourteen older non-obese, 11 older obese, 20
younger non-obese, and 20 younger obese adults completed walking trials at both a
self-selected and hurried speed. When walking at a hurried speed, older obese men
walked at a slower gait speed and exhibited lower frictional demands compared
both to older non-obese men and to younger obese men. No differences in required
friction were found between non-obese and obese younger adults. These results
suggest that the increased rate of falls among obese or older adults is not
likely due to a higher risk of slip initiation.
PMID- 28411742
TI - A biomechanical and physiological study of office seat and tablet device
interaction.
AB - Twenty subjects performed typing tasks on a desktop computer and touch-screen
tablet in two chairs for an hour each, and the effects of chair, device, and
their interactions on each dependent measure were recorded. Biomechanical
measures of muscle force, spinal load, and posture were examined, while
discomfort was measured via heart rate variability (HRV) and subjective reports.
HRV was sensitive enough to differentiate between chair and device interactions.
Biomechanically, a lack of seat back mobility forced individuals to maintain an
upright seating posture with increased extensor muscle forces and increased
spinal compression. Effects were exacerbated by forward flexion upon interaction
with a tablet device or by slouching. Office chairs should be designed with both
the human and workplace task in mind and allow for reclined postures to off-load
the spine. The degree of recline should be limited, however, to prevent decreased
lumbar lordosis resulting from posterior hip rotation in highly reclined
postures.
PMID- 28411743
TI - Psychophysiological responses to short-term cooling during a simulated monotonous
driving task.
AB - For drivers on monotonous routes, cognitive fatigue causes discomfort and poses
an important risk for traffic safety. Countermeasures against this type of
fatigue are required and thermal stimulation is one intervention method.
Surprisingly, there are hardly studies available to measure the effect of cooling
while driving. Hence, to better understand the effect of short-term cooling on
the perceived sleepiness of car drivers, a driving simulator study (n = 34) was
conducted in which physiological and vehicular data during cooling and control
conditions were compared. The evaluation of the study showed that cooling applied
during a monotonous drive increased the alertness of the car driver. The
sleepiness rankings were significantly lower for the cooling condition.
Furthermore, the significant pupillary and electrodermal responses were
physiological indicators for increased sympathetic activation. In addition,
during cooling a better driving performance was observed. In conclusion, the
study shows generally that cooling has a positive short-term effect on drivers'
wakefulness; in detail, a cooling period of 3 min delivers best results.
PMID- 28411744
TI - Effects of transit bus interior configuration on performance of wheeled mobility
users during simulated boarding and disembarking.
AB - The emergence of low-floor bus designs and related regulatory standards in the
U.S. have resulted in substantial improvements in public transit accessibility.
However, passengers using wheeled mobility devices still experience safety
concerns and inefficiencies in boarding, disembarking, and interior circulation
on low-floor buses. This study investigates effects of low-floor bus interior
configuration and passenger crowding on boarding and disembarking efficiency and
safety. Users of manual wheelchairs (n = 18), powered wheelchairs (n = 21) and
electric scooters (n = 9) simulated boarding and disembarking in three interior
layout configurations at low and high passenger crowding conditions on a full
scale laboratory mock-up of a low-floor bus. Dependent measures comprised task
times and critical incidents during access ramp use, fare payment, and movement
to and from the doorway and wheeled mobility securement area. Individual times
for unassisted boarding ranged from 15.2 to 245.3 s and for disembarking ranged
from 9.1 to 164.6 s across layout and passenger crowding conditions.
Nonparametric analysis of variance showed significant differences and
interactions across vehicle design conditions, passenger load and mobility device
type on user performance. The configuration having electronic on-board fare
payment, rear-bus entrance doorways and adjacent device securement areas
demonstrated greatest efficiency and safety. High passenger load adversely
impacted efficiency and frequency of critical incidents during on-board
circulation across all three layouts. Findings have broader implications for
improving transit system efficiency and quality of service across the spectrum of
transit users.
PMID- 28411745
TI - When the going gets tough, the tough go colder!
PMID- 28411746
TI - The art of repair.
PMID- 28411747
TI - The impact of carotid or intracranial atherosclerosis on perioperative stroke in
patients undergoing open aortic arch surgery.
AB - OBJECTIVES: This study aimed to clarify the impact of carotid or intracranial
atherosclerosis on perioperative stroke in patients undergoing open aortic arch
surgery. METHODS: Between 2008 and 2015, 200 consecutive patients underwent
elective aortic arch surgery with selective antegrade cerebral perfusion and
moderate hypothermic circulatory arrest. Nonselective screening for carotid or
intracranial atherosclerosis was performed using carotid ultrasonography or
magnetic resonance angiography. Carotid or intracranial atherosclerosis was
classified as below moderate (0%-49% stenosis), moderate (50%-69%), or severe
(70%-100%). In patients with moderate or severe stenosis, cerebral hemodynamics
were evaluated using single-photon emission computed tomography with
acetazolamide. RESULTS: None of the 37 patients undergoing preoperative single
photon emission computed tomography with acetazolamide had impaired cerebral
hemodynamics. In-hospital mortality rate was 3.5% (7/200). Postoperative
neurologic morbidity included permanent stroke in 8 patients (4.0%) and transient
neurologic deficits in 27 patients (14%). Permanent stroke occurred in 3 of 159
patients (1.9%) with below moderate stenosis and 5 of 41 patients (12.2%) with
moderate or severe stenosis (P = .008). Seven of 8 patients (87.5%) with stroke
experienced multiple atherothrombotic embolizations, and 1 patient experienced a
stroke of unknown cause. In multivariate analysis, previous cerebrovascular
accident (odds ratio, 5.0; 95% confidence interval, 2.07-12.42; P = .0004) and
shaggy aorta (odds ratio, 4.2; 95% confidence interval, 1.58-10.98; P = .0045)
were significant determinants of neurologic morbidity. CONCLUSIONS: Embolism was
the major cause of permanent stroke in our patient population. Preoperative
craniocervical and aortic screening may aid in modifying the operative strategy
to reduce the occurrence of stroke.
PMID- 28411748
TI - Mitral stenosis with pulmonary hypertension: We should operate early.
PMID- 28411749
TI - Pulmonary hypertension and mitral valve disease: Still a beast.
PMID- 28411750
TI - Safety of air travel in the immediate postoperative period after anatomic
pulmonary resection.
AB - OBJECTIVE: The study objective was to determine whether air travel in the
immediate postoperative period after anatomic pulmonary resection is associated
with increased morbidity or mortality. METHODS: All patients undergoing anatomic
pulmonary resection at the Mayo Clinic (2005-2012) were identified and sent
surveys querying their mode of transportation home after hospital dismissal and
any complications encountered during or shortly after this travel. This included
pneumonia, hospital readmission, deep venous thrombosis/pulmonary embolism, and
specific pleural complications (pneumothorax, empyema, or chest tube placement).
We compared the results of patients returning home by conventional ground travel
with the results of patients using air travel. RESULTS: Surveys were sent to 1833
patients, and 817 responded (44.6% response rate). A total of 96 responders
(11.8%) used air travel (median distance, 1783 km; range, 486-9684 km) compared
with 278 km (range, 1-2618 km) for the 721 responders (88.2%) using ground travel
(P < .0001). Male patients used air travel more than female patients (14.4% vs
9.3%; P = .02). Otherwise, no significant differences were observed between the 2
groups. The median duration of hospitalization was 5 days in both groups using
air travel (range, 1-25 days) and ground travel (range, 1-42 days) (P = .83).
There was no mortality due to postdismissal travel. The rates of major
complication after hospital dismissal for those using air and ground travel were
8.3% and 7.8%, respectively (P = .87). CONCLUSIONS: Overall major complications
are rare in the immediate posthospital dismissal period after lung resection. Air
travel during this period was not associated with any significant increase in
risk of complications when compared with conventional ground transportation and
seems to be a safe option for patients after chest tube removal.
PMID- 28411751
TI - Notice of Correction.
PMID- 28411752
TI - Complex homograft aortic reconstruction: New recipes from old ingredients.
PMID- 28411753
TI - 2016 update to The American Association for Thoracic Surgery (AATS) consensus
guidelines: Ischemic mitral valve regurgitation.
PMID- 28411754
TI - New common ground: EUS-guided portal pressure measurements as a bridge between
endoscopy and hepatology.
PMID- 28411755
TI - Combination pharmacoprophylaxis for post-ERCP pancreatitis: working toward an
evidence base.
PMID- 28411756
TI - Pancreatic cyst guidelines: Which one to live by?
PMID- 28411757
TI - Impact of endoscopist training on postcolonoscopy colorectal cancer rate.
PMID- 28411758
TI - Postcolonoscopy colorectal carcinoma.
PMID- 28411759
TI - Response.
PMID- 28411760
TI - Erratum.
PMID- 28411761
TI - EUS-guided biliary drainage: moving into a new era of biliary drainage.
PMID- 28411762
TI - POEM outcomes: How long is long enough?
PMID- 28411763
TI - Is timing everything in the management of acute upper GI bleeding?
PMID- 28411764
TI - Early gastric cancer in super-agers: To treat or not to treat?
PMID- 28411765
TI - Hepatic artery disease and anastomotic bile leaks after liver transplantation:
shining the light on the true Achilles' heel.
PMID- 28411766
TI - A review of the impact of patch testing on quality of life in allergic contact
dermatitis.
PMID- 28411767
TI - Low risk of hemorrhagic complications after obtaining diagnostic skin biopsy
specimens in a cohort of thrombocytopenic inpatients.
PMID- 28411768
TI - Who wrote this paper? The ethical issues of authorship.
PMID- 28411769
TI - Introducing the JAAD Virtual Journal Club.
PMID- 28411770
TI - Erratum to "Reporting adverse events related to cosmetic products".
PMID- 28411771
TI - Psychocutaneous disease: Clinical perspectives.
AB - Psychocutaneous disease, defined in this review as primary psychiatric disease
with skin manifestations, is commonly encountered in dermatology. Dermatologists
can play an important role in the management of psychocutaneous disease because
patients visit dermatology for treatment of their skin problems but often refuse
psychiatric intervention. This review describes common psychocutaneous syndromes,
including delusional, factitious, obsessive-compulsive and related, and eating
disorders, as well as psychogenic pruritus, cutaneous sensory (pain) syndromes,
posttraumatic stress disorder, and sleep-wake disorders. The updated
classification of these disorders in the Diagnostic and Statistical Manual of
Mental Disorders, 5th edition is included. Strategies for management are
reviewed.
PMID- 28411772
TI - Psychocutaneous disease: Pharmacotherapy and psychotherapy.
AB - Building a strong therapeutic alliance with the patient is of utmost importance
in the management of psychocutaneous disease. Optimal management of
psychocutaneous disease includes both pharmacotherapy and psychotherapy. This
article reviews psychotropic medications currently used for psychocutaneous
disease, including antidepressants, antipsychotics, mood stabilizers, and
anxiolytics, with a discussion of relevant dosing regimens and adverse effects.
Pruritus management is addressed. In addition, basic and complex forms of
psychotherapy, such as cognitive-behavioral therapy and habit-reversal training,
are described.
PMID- 28411773
TI - Commentary: The quest for an improved risk stratification tool for patients with
melanoma.
PMID- 28411774
TI - Nail removal in pachyonychia congenita: Patient-reported survey outcomes.
PMID- 28411775
TI - Comparing the sensitivity of auramine-rhodamine fluorescence to polymerase chain
reaction in the detection of Mycobacterium leprae in Fite-negative tissue
sections.
PMID- 28411776
TI - Establishment of a dermatology global health outreach and residency partnership
program in Guatemala.
PMID- 28411777
TI - A survey-based study of management of longitudinal melanonychia amongst attending
and resident dermatologists.
PMID- 28411778
TI - Lack of efficacy of topical timolol for cutaneous telangiectasias in patients
with hereditary hemorrhagic telangiectasia: Results of a pilot study.
PMID- 28411779
TI - Prescribing propranolol for infantile hemangioma: Assessment of dosing errors.
PMID- 28411788
TI - Intralesional corticosteroid therapy for relapsing polychondritis.
PMID- 28411789
TI - Significant cost savings from treating peristomal irritant contact dermatitis
with an over-the-counter spray.
PMID- 28411790
TI - The use of gentian violet 2% solution to identify holes in the deep margin of
tissue excised during Mohs micrographic surgery.
PMID- 28411791
TI - Preventing disruption of surgical dressings in patients with cognitive
impairment.
PMID- 28411792
TI - Surgical staples for hemostasis during scalp surgery.
PMID- 28411793
TI - Conclusions about atopic dermatitis persistence might be premature.
PMID- 28411794
TI - Reply to: "Conclusions about atopic dermatitis persistence might be premature".
PMID- 28411795
TI - Heterogeneity of data included in meta-analysis on persistence of atopic
dermatitis changes interpretation.
PMID- 28411796
TI - Reply to: "Heterogeneity of data included in meta-analysis on persistence of
atopic dermatitis alters interpretation".
PMID- 28411797
TI - A label-free fluorescence turn-on assay for glutathione detection by using MnO2
nanosheets assisted aggregation-induced emission-silica nanospheres.
AB - Glutathione (GSH) serves several vital biological functions and its abnormal
levels are associated with many diseases. Simple and sensitive methods capable of
detecting GSH are desired for better understanding the mechanism of diseases. In
this work, a label-free MnO2 nanosheets assisted aggregation-induced emission
(AIE)-silica nanospheres (SiO2 NPs) nanoprobe for fluorescent "turn-on" detection
of GSH with high sensitivity was reported for the first time. The anionic
tetraphenylethylene derivative 3 (TPE3) was synthesized and employed as the AIE
active probe, which can be aggregated on the uncoated amino-functionalized SiO2
NPs to form AIE-SiO2 NPs and emitted strong fluorescence. Negatively charged MnO2
nanosheets were employed as both positive charge protectors for amino
functionalized SiO2 NPs and recognition units for GSH. The presence of GSH could
selectively reduce MnO2 nanosheets to Mn2+, thus releasing the amino
functionalized SiO2 NPs and exposure its positive charges. Accordingly, the TPE3
could be aggregated on the exposured amino-functionalized SiO2 NPs to form AIE
SiO2 NPs and emitted strong fluorescence. The proposed assay is simple, fast, low
cost, and highly sensitive with a detection limit of 200nM for GSH. The assay was
further applied in human serum samples for the detection of GSH with satisfactory
results, demonstrating its promising application in practical biological samples.
PMID- 28411798
TI - Polyelectrolyte mediated nano hybrid particle as a nano-sensor with outstandingly
amplified specificity and sensitivity for enzyme free estimation of cholesterol.
AB - As a proof of concept, here it is established that curcumin integrated chitosan
oligosaccharide lactate (COL) self-assembles on silica nanoparticle surface to
form nano hybrid particles (NHPs). These NHPs have size in the ranges of 25-35nm
with silica nanoparticle as its core and curcumin-COL as outer layer having
thickness of 4-8nm. The fluorescence intensity of these NHPs are found to be
quenched and emission maximum is ~50nm red shifted compared to free curcumin
implying inner filter effect and/or homo-FRET between curcumin molecules present
on the surface of individual nano hybrid particle. Although fluorescence of free
curcumin is remarkably quenched by Hg2+/Cu2+ ions due to chelation through keto
enol form, the fluorescence of NHPs is unaffected by Hg2+/Cu2+ ion that boosts
analytical selectivity. The fluorescence intensity is outstandingly enhanced in
the presence of cholesterol but is not influenced by ascorbic acid, uric acid,
glucose, albumin, lipid and other potential interfering substances that either
obstruct during enzymatic reaction or affect fluorescence of free curcumin. Thus,
NHPs outstandingly improve analytical specificity, selectivity and sensitivity
during cholesterol estimation compared to free curcumin. The interaction between
cholesterol and NHPs is found to be a combination of ground state electrostatic
interaction through the free hydroxyl group of cholesterol along with hydrophobic
interaction between NHPs and cholesterol and excited state interaction. The
proposed cholesterol biosensor illustrates a wider linear dynamic range, 0.002
10mmolL-1, (upper limit is due to lack of solubility of cholesterol) needed for
biomedical application and better than reported values during enzymatic reaction.
In addition, the NHPs are found to be photo-stable potentially making it suitable
for simple, quick and cost-effective cholesterol estimation and opening an
alternative approach other than enzymatic reaction using nano hybrid structure to
tune analytical specificity, selectivity and sensitivity of probe molecule.
PMID- 28411799
TI - Selective detection of ZnO nanoparticles in aqueous suspension by capillary
electrophoresis analysis using dithiothreitol and L-cysteine adsorbates.
AB - The UV detection sensitivity of ZnO nanoparticles in capillary electrophoresis
(CE) analysis was selectively enhanced, by 27 or 19 folds, after adsorption of
dithiothreitol (DTT) or cysteine (Cys) in 10mM sodium phosphate buffer.
Adsorption equilibrium was reached within 90min for DTT but only 10min for Cys.
The adsorption process was best modeled by the Langmuir isotherm, indicating the
formation of a monolayer of DTT or Cys on the surface of ZnO nanoparticles. The
selectivity of DTT and Cys towards ZnO nanoparticles was tested using alumina
(Al2O3), ceria (CeO2), silica (SiO2) and titania (TiO2) nanoparticles. No changes
in the CE-UV peak area of either adsorbates or nanoparticles were observed,
indicating a lack of adsorption. Dynamic light scattering (DLS) provided similar
evidence of the selectivity of both adsorbates towards ZnO. Cys also improved the
colloidal stability of ZnO nanoparticles by breaking down the aggregates, as
evidenced by a reduction of their average hydrodynamic diameter. This new
analytical approach provides a simple and rapid methodology to detect ZnO
nanoparticles selectively by CE-UV analysis with enhanced sensitivity.
PMID- 28411800
TI - Quantification of copper content with laser induced breakdown spectroscopy as a
potential indicator of offal adulteration in beef.
AB - Laser induced breakdown spectroscopy (LIBS) is an emerging technique in the field
of food analysis which provides various advantages such as minimal sample
preparation, chemical free, rapid detection, provision of spatial information and
portability. In this study, LIBS was employed for quantitative analysis of copper
content in minced beef samples spiked with beef liver over three independent
batches. Copper content was determined with graphite furnace atomic absorption
spectroscopy (GFAAS) in order to obtain reference values for modelling. Partial
least square regression (PLSR) was performed to build a calibration and
validation model. A calibration model with a high Rcv2 of 0.85 and a RMSECV of
43.5ppm was obtained, confirming a good fit for the model. The validation model
showed a good prediction accuracy with a high Rp2 of 0.85 and RMSEP of 36.8ppm.
Moreover, on a further study to evaluate the spatial capabilities, LIBS was able
to successfully map copper content within a pellet, indicating the suitability of
LIBS to provide spatial information and therefore potential use on heterogeneous
samples. Overall, it can be concluded that LIBS combined with chemometrics
demonstrates potential as a quality monitoring tool for the meat processing
industry.
PMID- 28411801
TI - Optimization of gold nanoparticle-based real-time colorimetric assay of
dipeptidyl peptidase IV activity.
AB - Dipeptidyl peptidase IV (DPP-IV also referred to as CD-26) is a serine protease
enzyme with remarkable diagnostic and prognostic value in a variety of health and
disease conditions. Herein, we describe a simple and real-time colorimetric assay
for DPP-IV/CD-26 activity based on the aggregation of gold nanoparticles (AuNPs)
functionalized with the peptide substrates: Gly-Pro-Asp-Cys (GPDC) or Val-Pro
ethylene diamine-Asp-Cys (VP-ED-DC). Cleavage of the substrates by DPP-IV
resulted in aggregation of the AuNPs with accompanying color change in the
solution from red to blue that was monitored using either a UV-visible
spectrophotometer or by the naked eye. Factors, such as time course of the
reaction, stability of the functionalized AuNPs and the structure of the
substrate that influence the cleavage reaction in solution were investigated. The
effects of potential interference from serum proteins (lysozyme, thrombin and
trypsin) on the analytical response were negligible. The detection limits when
GPDC or VP-EN-DC functionalized AuNPs were used for DPP-IV assay were 1.2U/L and
1.5U/L, respectively. The VP-EN-DC method was preferred for the quantitative
determination of DPP-IV activity in serum because of its wide linear range 0
30U/L compared to 0-12U/L for the GPDC assay. Recoveries from serum samples
spiked with DPP-IV activity, between 5 and 25U/L, and using the VP-EN-DC modified
AuNPs method ranged between 83.6% and 114.9%. The two colorimetric biosensors
described here are superior to other conventional methods because of their
simplicity, stability, selectivity and reliability.
PMID- 28411802
TI - Protein separation through preliminary experiments concerning pH and salt
concentration by tube radial distribution chromatography based on phase
separation multiphase flow using a polytetrafluoroethylene capillary tube.
AB - Protein mixtures were separated using tube radial distribution chromatography
(TRDC) in a polytetrafluoroethylene (PTFE) capillary (internal diameter=100um)
separation tube. Separation by TRDC is based on the annular flow in phase
separation multiphase flow and features an open-tube capillary without the use of
specific packing agents or application of high voltages. Preliminary experiments
were conducted to examine the effects of pH and salt concentration on the phase
diagram of the ternary mixed solvent solution of water-acetonitrile-ethyl acetate
(8:2:1 volume ratio) and on the TRDC system using the ternary mixed solvent
solution. A model protein mixture containing peroxidase, lysozyme, and bovine
serum albumin was analyzed via TRDC with the ternary mixed solvent solution at
various pH values, i.e., buffer-acetonitrile-ethyl acetate (8:2:1 volume ratio).
Protein was separated on the chromatograms by the TRDC system, where the elution
order was determined by the relation between the isoelectric points of protein
and the pH values of the solvent solution.
PMID- 28411803
TI - A quantitative method for detecting DNA methylation over targeted genomic regions
using isotope dilution liquid chromatography tandem mass spectrometry.
AB - Aberrant DNA methylation is associated with various diseases. Quantitative
analysis of regional DNA methylation levels of some specific genes would aid in
diseases diagnosis and risk stratification. In this study, we developed a robust
method for detecting DNA methylation level over targeted genomic regions using
nucleobases quantification in bisulfite amplicons by isotope dilution liquid
chromatography tandem mass spectrometry coupled with a simple equation. This
method had wide detection range (from 0% to 100% methylation) and high accuracy
while more time-saving compared to clonal bisulfite sequencing method. The
application for clinical tissue samples showed good applicability and cost
effectiveness. This analytical method is suitable for quantifying average DNA
methylation level over targeted genomic regions and expected to be a useful tool
for detecting DNA methylation biomarkers.
PMID- 28411804
TI - Carrot-derived carbon dots modified with polyethyleneimine and nile blue for
ratiometric two-photon fluorescence turn-on sensing of sulfide anion in
biological fluids.
AB - In this article, a facile and green synthesis of carbon dots (CDs) was developed
by using natural carrot as new carbon source. After direct hydrothermal
carbonization for 5h at 180 degrees C, CDs were prepared facilely. Then, CDs were
conjugated with polyethyleneimine (PEI) and Nile Blue (NB) chloride to produce
CDs/PEI/NB nanocomposites under electrostatic interactions. Upon excitation at
800nm, two-photon fluorescence (TPF) of the nanocomposites was observed, with TPF
peaks of CDs at 415nm and NB at 675nm. The addition of Cu2+ could lead to TPF
quenching of CDs via inner filter effect, but hardly any impacted on TPF of NB.
Afterward, the added S2- combined with Cu2+ to form stable species that caused
the separation of Cu2+ from CDs surface and the TPF recovery of CDs, with
negligible effects on TPF of NB. Herein, a new CDs-based ratiometric TPF turn-on
probe of S2- was developed and showed a good linear relationship (R2 =0.9933)
between ratiometric TPF intensity (I415/I675) and S2- concentration (0.1-8.0MUM),
with a low detection limit of 0.06MUM. This probe was highly selective and
sensitive toward S2- over potential interferences in real biological fluids, with
high detection recoveries.
PMID- 28411805
TI - A ratiometric fluorescent probe for rapid and sensitive detection of biothiols in
fetal bovine serum.
AB - Herein, a ratiometric turn-on fluorescent probe for sensitive detection of
biothiols was designed. The probe consisted of two parts: one was rhodamine B
serving as a fluorescence reference, and the other was coumarin derivative as the
responsive fluorophore with an acrylate group for biothiols recognition. The
response was based on the mechanism of Michael addition and intramolecular
cyclization reaction, and the probe showed ratiometric and sensitive response to
biothiols. Especially, the detection limit of this probe for cysteine was found
to be 0.13MUMU. More importantly, the probe showed the advantage of fast
response, of which the fluorescence intensity can reach the maximum within 10min.
The ratiometric fluorescent probe has been successfully applied for the
determination of biothiols in fetal bovine serum samples and the result was in
good agreement with that tested by Ellman method.
PMID- 28411806
TI - Automated alkaline-induced salting-out homogeneous liquid-liquid extraction
coupled with in-line organic-phase detection by an optical probe for the
determination of diclofenac.
AB - A fully automated alkaline-induced salting-out homogeneous liquid-liquid
extraction (AI-SHLLE) procedure coupled with in-line organic-phase detection by
an optical probe has been suggested. Diclofenac was used as a proof-of-concept
analyte. The method is based on the oxidation of diclofenac with potassium
ferricyanide in an alkaline medium followed by separation of the acetonitrile
phase from the homogeneous sample solution and simultaneous extraction of the
derivative. Sodium hydroxide serves as both the alkaline agent for the
derivatization of diclofenac and as the salting-out agent for the acetonitrile
rich phase formation. Absorbance of the derivative in the acetonitrile-rich phase
was measured in-line using an optical probe. The calibration graph was linear
over the range of 2.5-60umolL-1 with the regression coefficient equal to 0.9997.
The LOD calculated from the calibration plot based on 3sigma was 0.8umolL-1. The
sample throughput was 7 samplesh-1. The method was applied for the determination
of diclofenac in spiked saliva samples and pharmaceutical preparations and the
results were compared with those obtained by the reference method.
PMID- 28411807
TI - A sensitive and disposable indium tin oxide based electrochemical immunosensor
for label-free detection of MAGE-1.
AB - MAGE-1 (MAGE, for melanoma antigen), was identified by virtue of its processing
and cell surface expression as a tumor-specific peptide bound to major
histocompatibility complexes which was reactive with autolytic T cells. 3
Glycidoxypropyltrimethoxysilane (3-GOPS) is frequently employed for the
preparation of dense heterometal hybrid polymers which are used, e.g., for hard
coatings of organic polymers and contact lens materials in the optical industry.
In this study, we have improved a new immunological biosensor with indium tin
oxide (ITO). Then, Anti-MAGE-1 antibody was covalently immobilized with 3-GOPS
which formed a self-assembled monolayers (SAMs) on modified ITO electrodes.
Analytical characteristics such as square wave voltammetry, linear determination
range, repeatability, reproducibility and regeneration of biosensors are
determined. All characterization steps are monitored by electrochemical impedance
spectroscopy (EIS), cyclic voltammetry (CV). The developed biosensor has wide
determination range (0.5fg-15fg/mL). To investigate long shelf life of the
fabricated biosensor, the immunosensors were stored at 4 degrees C for periods
ten weeks. Futhermore, binding kinetics of MAGE1 to antiMAGE-1 is monitored by
single frequency technique in real time. Additionally, Kramer's-Kronig transform
was used to understand whether the impedance spectra of biosensor system are
affected from the variation that occurred because of external factor.
Morphological characteristics of constructed biosensor were observed by scanning
electron microscopy. Real human serum samples were also analyzed by the proposed
biosensor, successfully. A commercial ELISA kit was also used as a reference
method to validate the results obtained by the biosensor. Finally, this biosensor
was tried in real blood sample and that showed it could be utilized in clinical
applications. This biosensor can be preferred due to it has a wide linear range
and it can be prepared easily.
PMID- 28411808
TI - Validation of a new method by nano-liquid chromatography on chip tandem mass
spectrometry for combined quantitation of C3f and the V65 vitronectin fragment as
biomarkers of diagnosis and severity of osteoarthritis.
AB - Microfluidic liquid chromatography coupled to a nanoelectrospray source ion trap
mass spectrometry was used for the absolute and simultaneous quantitation of C3f
and the V65 vitronectin fragment in serum. The method was first carefully
optimized and then validated in serum biological matrix. Stable isotopes for the
two biomarkers of interest were used as stable isotope labeled peptide standards.
A weighted 1/x2 quadratic regression for C3f and a weighted 1/x quadratic
regression for the V65 vitronectin peptide were selected for calibration curves.
Trueness (with a relative bias <10%), precision (repeatability and intermediate
precision <15%) and accuracy (risk <15%) of the method were successfully
demonstrated. The linearity of results was validated in the concentration range
of 2.5-200ng/mL for C3f and 2.5-100ng/mL for the V65 vitronectin fragment. Serum
samples (n=147) classified in 7 groups [(healthy volunteers, OA with 5 grades of
severity and rheumatoid arthritis (RA) patients] were analyzed with our new
quantitative method. Our data confirm that C3f and the V65 vitronectin fragment
are biomarkers of OA severity, but also that C3f fragment is further related to
OA severity whereas the V65 vitronectin fragment is more related to early OA
detection.
PMID- 28411809
TI - Temperature sensing and bio-imaging applications based on polyethylenimine/CaF2
nanoparticles with upconversion fluorescence.
AB - Rare earth ion-doped upconversion nanoparticles (UCNPs) have become a research
hotspot for their applications such as nano-thermometry and bio-imaging. Here we
report one pot solvothermal synthesis of polyethylenimine (PEI) coated CaF2:
1%Er3+, 2%Yb3+ UCNPs with good water-solubility and biocompatibility. The
nanoparticles show a spherical shape with an average size of 40nm and display
intense green light (Yb3+ and Er3+) under the 980nm irradiation. The maximum
sensitivity of temperature sensing in the biological temperature range is
obtained to be 0.00215K-1 using the fluorescence intensity ratio (FIR) technique.
Furthermore, after the UCNPs are incubated with Hela cancer cells for 6h, the
obvious green sign from Er3+ can be observed under the excitation at 980nm. All
the experimental results imply that the PEI/CaF2: 1%Er3+, 2%Yb3+ nanoparticles
are excellent candidates for nano-thermometry and have good potential for
biological applications.
PMID- 28411810
TI - Multivariate curve resolution applied to kinetic-spectroscopic data matrices: Dye
determination in foods by means of enzymatic oxidation.
AB - In this work, the combination of chemometric techniques with kinetic
spectroscopic data allowed quantifying two dyes (tartrazine and carminic acid) in
complex matrices as mustard, ketchup, asparagus soup powder, pumpkin soup powder,
plum jam and orange-strawberry juice. Quantitative analysis was performed without
the use of tedious sample pretreatment, due to the achievement of the second
order advantage. The results obtained showed an improvement in simplicity, speed
and cost with respect to usual separation techniques, allowing to properly
quantifying these dyes obtaining limits of detection below 0.6mgL-1. In addition,
to the best of our knowledge, is the first time that kinetic-spectroscopic data
are obtained from the action of laccase for analytical purposes.
PMID- 28411811
TI - A novel strategy for global mapping of O-GlcNAc proteins and peptides using
selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry
identification.
AB - O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic
and mitochondrial proteins. It serves as a major nutrient sensor to regulate
numerous biological processes including transcriptional regulation, cell
metabolism, cellular signaling, and protein degradation. Dysregulation of
cellular O-GlcNAcylated levels contributes to the etiologies of many diseases
such as diabetes, neurodegenerative disease and cancer. However, deeper insight
into the biological mechanism of O-GlcNAcylation is hampered by its extremely low
stoichiometry and the lack of efficient enrichment approaches for large-scale
identification by mass spectrometry. Herein, we developed a novel strategy for
the global identification of O-GlcNAc proteins and peptides using selective
enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
Standard O-GlcNAc peptides can be efficiently enriched even in the presence of
500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry
with a low nanogram detection sensitivity. This strategy successfully achieved
the first large-scale enrichment and characterization of O-GlcNAc proteins and
peptides in human urine. A total of 474 O-GlcNAc peptides corresponding to 457 O
GlcNAc proteins were identified by mass spectrometry analysis, which is at least
three times more than that obtained by commonly used enrichment methods. A large
number of unreported O-GlcNAc proteins related to cell cycle, biological
regulation, metabolic and developmental process were found in our data. The above
results demonstrated that this novel strategy is highly efficient in the global
enrichment and identification of O-GlcNAc peptides. These data provide new
insights into the biological function of O-GlcNAcylation in human urine, which is
correlated with the physiological states and pathological changes of human body
and therefore indicate the potential of this strategy for biomarker discovery
from human urine.
PMID- 28411812
TI - Quantifying endogenous androgens, estrogens, pregnenolone and progesterone
metabolites in human urine by gas chromatography tandem mass spectrometry.
AB - A method for the quantitation of 22 urinary steroids (androgens, estrogens and
the main pregnenolone and progesterone metabolites) by means of gas
chromatography tandem mass spectrometry using a triple quadrupole analyzer has
been developed. Two different enzymatic hydrolysis protocols were investigated;
one capable of releasing steroids present as both sulfates and glucuronides
(total fraction), and another with beta-glucuronidase activity only. After
selecting adequate internal standards and choosing the optimal instrumental
parameters, i.e. chromatographic separation and ion transition conditions, the
method was fully validated using both hydrolysis protocols. The method was shown
to be linear (r >0.99) in the range of endogenous concentrations for all studied
steroids with extraction recoveries higher than 80%. The use of labeled internal
standards allowed for both a correct quantification and the evaluation of the
rate of deconjugation for sulfates and glucuronides in every sample. In general,
the sensitivity of the method was suitable for the detection of the endogenous
levels, with limits of quantification ranging from 0.1 to 20ng/mL. Accuracies
ranging from 80% to 120%, and relative standard deviations below 25% in intra-
and inter- assay experiments were found for most of the analytes. The
applicability of the validated method was tested by quantifying twenty-two
metabolites in 24-h urine samples collected from healthy individuals. The ranges
for the excretion of steroids in the total and glucuronide fractions obtained
with the new method were compared with those available in the literature. By
comparing the figures in both fractions, an estimation of the percentage that the
sulfation represents for each steroid was also calculated. The presence of side
enzymatic activities and the utility of the method for clinical studies as well
as for doping control analysis is discussed.
PMID- 28411813
TI - Voltammetric determination of trace amounts of diacetyl at a mercury meniscus
modified silver solid amalgam electrode following gas-diffusion microextraction.
AB - A new approach was developed for the determination of trace amounts of diacetyl
in food products using gas-diffusion microextraction (GDME) and subsequent
detection by differential pulse voltammetry (DPV) at a mercury meniscus modified
silver solid amalgam electrode (m-AgSAE). Diacetyl is a vicinal diketone
responsible for the buttery aroma in many fermented foods and beverages. Its
determination is important not only for evaluation of the final product quality
(note of mention: health related concerns were associated with continuous
diacetyl exposure) but also to monitor fermentation. GDME, a technique combining
gas-diffusion and microextraction, particularly aimed to volatile and semi
volatile analytes, seemed the best way to selective extract diacetyl. A solution
of 0.05% o-phenylenediamine (OPDA) prepared in a Britton-Robinson buffer (pH 5.0)
was chosen as the extracting solution. This solution simultaneously extracts, pre
concentrates and derivatizes diacetyl to 2,3-dimethylquinoxaline (DMQ), enhancing
the extraction selectivity and making the analyte electroactive. After finding
the optimum conditions for the extraction process (10min at 60 degrees C with
1.0mL of OPDA at pH 5.0), the DPV measurements at the m-AgSAE were conducted with
a scan rate of 7mVs-1, a modulation amplitude of 50mV and a modulation time of
100ms. Under these conditions, the resulting DMQ could be easily measured at a
potential of -0.6V vs. Ag|AgCl (3molL-1 KCl). The amalgam electrode keeps the
advantages of classic mercury electrodes, like high sensitivity, while being
environmentally friendly. The GDME/m-AgSAE produced suitable method features for
the determination of low amounts of diacetyl (as DMQ) in alcoholic beverages, and
in fact, to the best of our knowledge, the limit of quantification of 0.18ugL-1
is one of the lowest reported in literature.
PMID- 28411814
TI - Nanocoating cellulose paper based microextraction combined with nanospray mass
spectrometry for rapid and facile quantitation of ribonucleosides in human urine.
AB - A rapid and facile analytical method for quantification of ribonucleosides in
human urine was developed by the combination of nanocoating cellulose paper based
microextraction and nanoelectrospray ionization-tandem mass spectrometry (nESI
MS/MS). Cellulose paper used for microextraction was modified by nano-precision
deposition of uniform ultrathin zirconia gel film using a sol-gel process. Due to
the large surface area of the cellulose paper and the strong affinity between
zirconia and the cis-diol compounds, the target analytes were selectively
extracted from the complex matrix. Thus, the detection sensitivity was greatly
improved. Typically, the nanocoating cellulose paper was immersed into the
diluted urine for selective extraction of target analytes, then the extracted
analytes were subjected to nESI-MS/MS detection. The whole analytical procedure
could be completed within 10min. The method was evaluated by the determination of
ribonucleosides (adenosine, cytidine, uridine, guanosine) in urine sample. The
signal intensities of the ribonuclesides extracted by the nanocoating cellulose
paper were greatly enhanced by 136-459-folds compared with the one of the
unmodified cellulose paper based microextraction. The limits of detection (LODs)
and the limits of quantification (LOQs) of the four ribonucleosides were in the
range of 0.0136-1.258MUgL-1 and 0.0454-4.194MUgL-1, respectively. The recoveries
of the target nucleosides from spiked human urine were in the range of 75.64
103.49% with the relative standard deviations (RSDs) less than 9.36%. The results
demonstrate the potential of the proposed method for rapid and facile
determination of endogenous ribonucleosides in urine sample.
PMID- 28411815
TI - Automation of sample processing for ICP-MS determination of 90Sr radionuclide at
ppq level for nuclear technology and environmental purposes.
AB - 90Sr is a widely determined radionuclide for environmental purposes, nuclear
waste control, and can be also monitored in coolants in nuclear reactor plants.
In the developed method, the ICP-MS detection was employed together with sample
processing in sequential injection analysis (SIA) setup, equipped with a lab-on
valve with mechanized renewal of sorbent bed for solid-phase extraction. The
optimized conditions of determination included preconcentration of 90Sr on cation
exchange column and removal of different type of interferences using extraction
Sr-resin. The limit of detection of the developed procedure depends essentially
on the configuration of the employed ICP-MS spectrometer and on the available
volume of the sample to be analyzed. For 1L initial sample volume, the method
detection limit (MDL) value was evaluated as 2.9ppq (14.5BqL-1). The developed
method was applied to analyze spiked river water samples, water reference
materials, and also simulated and real samples of the nuclear reactor coolant.
PMID- 28411816
TI - A novel metal-organic framework composite MIL-101(Cr)@GO as an efficient sorbent
in dispersive micro-solid phase extraction coupling with UHPLC-MS/MS for the
determination of sulfonamides in milk samples.
AB - As a novel material, metal-organic framework/graphite oxide (MIL-101(Cr)@GO) has
great potential for the pretreatment of trace analytes. In the present study, MIL
101(Cr)@GO was synthesized using a solvothermal synthesis method at the nanoscale
and was applied as sorbent in the dispersive micro-solid phase extraction (DMSPE)
for the enrichment of the trace sulfonamides (SAs) from milk samples for the
first time. Several experimental parameters including kinds of sorbents, the
effect of pH, the amount of MIL-101(Cr)@GO, ionic strength, adsorption time,
desorption solvent and desorption time were investigated. Under the optimal
conditions, the linear ranges were from 0.1 to 10MUg/L, 0.2-20MUg/L or 0.5
50MUg/L for the analytes with regression coefficients (r) from 0.9942 to 0.9999.
The limits of detection were between 0.012 and 0.145MUg/L. The recoveries ranged
from 79.83% to 103.8% with relative standard deviations (RSDs)<10% (n=3). MIL
101(Cr)@GO exhibited remarkable advantages compared to MIL-101(Cr), MIL-100(Fe),
activated carbon and other sorbent materials used in pretreatment methods. A
simple, rapid, sensitive, inexpensive and less solvent consuming method of DMSPE
ultra-high performance liquid chromatography-tandem mass spectrometry (DMSPE
UHPLC-MS/MS) was successfully applied to the pre-concentration and determination
of twelve SAs in milk samples.
PMID- 28411817
TI - Trimethyl-beta-cyclodextrin-encapsulated monolithic capillary columns:
Preparation, characterization and chiral nano-LC application.
AB - Trimethylated-beta-cyclodextrin (TM-beta-CD) was encapsulated within several
polymer monolithic capillary columns for reversed-phase chiral nano-liquid
chromatography (nano-LC). The monolithic phases were prepared using the one-pot
in situ copolymerization of ethylene glycol dimethacrylate (EDMA), glycidyl
methacrylate (GMA) monomers and 1-propanol, 1,4-butanediol as progenic solvents
in presence of TM-beta-CD solution within fused silica capillaries (150um I.D.).
The obtained chiral monolithic stationery phases were characterized by scanning
electron microscopy (SEM), N2 adsorption/desorption isotherms, wide angle x-ray
diffraction (WAXRD), thermogravimetric analysis (TGA) and differential thermal
analysis (DTA). The materials characterization demonstrated that monolithic
phases with higher concentration of TM-beta-CD have relatively larger surface
area, smaller pore size and larger total pore volume compared to those with lower
concentration TM-beta-CD. The prepared columns were tested for their
enantioseparation efficiency of a range of racemic pharmaceuticals. The screening
results demonstrated the potential of functionalizing polymer monolithic
stationary phases with TM-beta-CD using the in situ encapsulation approach.
PMID- 28411818
TI - Rapid evaporative ionization mass spectrometry for high-throughput screening in
food analysis: The case of boar taint.
AB - Boar taint is a contemporary off-odor present in meat of uncastrated male pigs.
As European Member States intend to abandon surgical castration of pigs by 2018,
this off-odor has gained a lot of research interest. In this study, rapid
evaporative ionization mass spectrometry (REIMS) was explored for the rapid
detection of boar taint in neck fat. Untargeted screening of samples (n=150)
enabled discrimination between sow, tainted and untainted boars. The obtained
OPLS-DA models showed excellent classification accuracy, i.e. 99% and 100% for
sow and boar samples or solely boar samples, respectively. Furthermore, the
obtained models demonstrated excellent validation characteristics (R2(Y)=0.872
0.969; Q2(Y)=0.756-0.917), which were confirmed by CV-ANOVA (p<0.001) and
permutation testing. In conclusion, in this work for the first time highly
accurate and high-throughput (<10s) classification of tainted and untainted boar
samples was achieved, rendering REIMS a promising technique for predictive
modelling in food safety and quality applications.
PMID- 28411819
TI - An electrochemical bisphenol A sensor based on one step electrochemical reduction
of cuprous oxide wrapped graphene oxide nanoparticles modified electrode.
AB - Bisphenol A (BPA), as an important industrial material, has been widespread
concerned in recent years as its endocrine disrupting effect. This study reported
a novel bisphenol A sensor via a facile one step electrochemical reduction of
graphene oxide (rGO) and cuprous oxide (Cu2O) nanocomposite modified glassy
carbon electrodes. The characterization of the fabricated sensor was performed by
scanning electron microscopy and X-ray spectroscopy. The prepared Cu2O-rGO
electrode presented fast response, high sensitivity and low background current.
The response of BPA on prepared electrode was 2.15 times higher than reduced
graphene modified electrode. Under the optimized experimental parameters, the
detection range of the modified electrode was from 1*10-7 to 8*10-5 M and the
limit of detection was 5.3*10-8 M (S/N =3). The prepared Cu2O-rGO modified
electrode has been successfully used for detecting BPA in environmental water
samples.
PMID- 28411820
TI - Thrombin aptasensor enabled by Pt nanoparticles-functionalized Co-based metal
organic frameworks assisted electrochemical signal amplification.
AB - In this work, a Pt nanoparticles-functionalized Co-based metal organic frameworks
(PtNPs@Co(II)MOFs@PtNPs) was synthesized and applied in electrochemical
aptasensor for thrombin (TB) detection. First, the Co(II)MOFs@PtNPs were prepared
via the mixed solvothermal method, which consists of inner Pt nanoparticles
(PtNPs) encapsulated by aminofunctionalized Co(II)MOFs materials. Following that,
additional PtNPs were adsorbed on the surface of Co(II)MOFs@PtNPs, resulting in
the formation of PtNPs@Co(II)MOFs@PtNPs nanocomposite. The PtNPs@Co(II)MOFs@PtNPs
nanocomposites with a large surface area were implimented as nanocarriers to
immobilize a mass of TBA II for the formation of the TBA II bioconjugates that
could be captured onto the electrode surface by sandwich-type format. Moreover,
the PtNPs@Co(II)MOFs@PtNPs nanocomposites could directly use as redox tags for
charge-generating and electron-transporting with the electron transfer from
Co(II) to Co(III). Furthermore, in the presence of H2O2, the
PtNPs@Co(II)MOF@PtNPs could effectively catalyze H2O2 oxidation with improvement
electron transfer of redox probe, resulting in electrochemical signal
amplification. Based on the above superior advantages, TB was determined in the
concentration range from 0.1pM to 50nM with a detection limit of 0.33fM.
Furthermore, the excellent sensitivity and selectivity can be easily established
for quantitative analysis of other analytes.
PMID- 28411821
TI - Electrochemical discrimination of mints: The last Chinese emperors Kuang Hsu and
Hsuan T'ung monetary unification.
AB - An electrochemical methodology for discriminating monetary emissions, a recurrent
problem in much archaeological studies, is introduced. The method is based on the
record of voltammetric signatures of cuprite and tenorite corrosion products in
the patina using a minimally invasive nanosampling following the voltammetry of
immobilized particles methodology. A model for the depth variation of
voltammetric electrochemical parameters characterizing the composition of the
corrosion patinas is presented. This model permits to rationalize electrochemical
data and discriminate different monetary emissions. The application of this
technique, corroborated by electrochemical impedance spectroscopy (EIS) and
focusing ion beam-field emission scanning electron microscopy (FIB-FESEM-EDX), to
a series of 10 cash copper coins produced around the Kuang Hsu and Hsuan T'ung
last Chinese emperors permits to discern different provincial mints and reveals
that the monetary unification developed in this period was not uniform.
PMID- 28411822
TI - Label-free and sensitive assay for deoxyribonuclease I activity based on
enzymatically-polymerized superlong poly(thymine)-hosted fluorescent copper
nanoparticles.
AB - Deoxyribonuclease I (DNase I) is an important physiological indicator and
diagnostic biomarker, but traditional methods for assessing its activity are time
consuming, laborious, and usually radioactive. Herein, by effectively combining
the special functions of DNase I and terminal deoxynucleotidyl transferase (TdT),
a simple, green, cost-effective, label-free and ultrasensitive assay for DNase I
activity has been constructed based on superlong poly(thymine)-hosted copper
nanoparticles (poly T-CuNPs). In this strategy, a 3'-phosphorylated DNA primer is
designed to block TdT polymerization. After addition of DNase I, the primer could
be digested to release 3'-hydroxylated fragments, which could further be tailed
by TdT in dTTP pool with superlong poly T ssDNA for CuNPs formation. Fluorescence
measurements and gel electrophoresis demonstrated its feasibility for DNase I
analysis. The results indicated that with a size of 3-4nm, the CuNPs templated by
TdT-polymerized superlong poly T (>500 mer) had several advantages such as short
synthetic time (<5min), large Stokes shift (~275nm) and intense red fluorescence
emission. Under the optimal conditions, quantitative detection of DNase I was
realized, showing a good linear correlation between 0.02 and 2.0U/mL (R2=0.9928)
and a detection limit of 0.02U/mL. By selecting six other nucleases or proteins
as controls, an excellent specificity was also verified. Then, the strategy was
successfully applied to detect DNase I in diluted serum with a standard addition
method, thus implying its reliability and practicability for biological samples.
The proposed strategy might be promising as a sensing platform for related
molecular biology and disease studies.
PMID- 28411823
TI - Nucleic acid-controlled quantum dots aggregation: A label-free fluorescence turn
on strategy for alkaline phosphatase detection.
AB - Based on the controlled aggregation of quantum dots (QDs), a valid, reliable, and
label-free fluorescence turn-on strategy is established for the detection of
alkaline phosphatase activity. The aqueous solution of anionic QDs exhibits
intense fluorescence. However, the addition of cationic polymer (poly-1)
significantly quenched the fluorescence of the QDs via their induced aggregation.
While short 3'-phosphorylated DNA (DNA-P) could not be extended by terminal
deoxynucleotidyl transferase (TdT) and therefore, fluorescence of the QDs was
recovered negligibly. The effective elimination of phosphate group of DNA-P in
the presence of alkaline phosphatase (ALP) produced 3'-OH termini and the
resulting DNA could be sufficiently extended by TdT. The presence of greater
binding strength between the elongated DNA and poly-1 is very crucial to compete
with the poly-1/QDs aggregates and release the QDs. Turned-on fluorescence
emission is observed due to the efficient release of the QDs. A novel strategy
for alkaline phosphatase detection is therefore established. Our method is quite
sensitive and selective, as low as 0.1 mU/mL ALP can be easily detected.
PMID- 28411824
TI - Application of benchtop and portable near-infrared spectrometers for predicting
the optimum harvest time of Verbena officinalis.
AB - This study examined the applicability of near-infrared (NIR) spectroscopy coupled
with multivariate data analysis (MVA) to determine the ideal harvest time of
Verbena officinalis. NIR analyses were performed non-invasively on the fresh
plant material based on the quantification of the key constituents verbenalin and
verbascoside. Vibrational spectroscopic measurements were performed applying a
conventional NIR benchtop device as well as a laboratory independent handheld NIR
spectrometer. A novel high performance liquid chromatography (HPLC) method was
applied as a reference method. For both instruments partial least squares (PLS)
regression models were established performing cross validations (CV) and test-set
validations (TSV). Quality parameters obtained for the benchtop device revealed
that the newly established NIR method enabled reliable quantifications of the
main compounds verbenalin and verbascoside related to the dried and fresh plant
material. The results of the miniaturised spectrometer revealed that accurate
quantitative calibration models could be developed for verbascoside achieving a
comparable prediction power to the benchtop device. PLS models for verbenalin
were less precise suggesting the application of portable devices including a
different spectral range and resolution. The work demonstrated the feasibility of
NIR vibrational spectroscopy performing direct measurements on pharmaceutically
relevant fresh plant material enabling a quick and simple determination of the
ideal harvest time of Verbena officinalis.
PMID- 28411825
TI - Volatile profiles of green Spanish-style table olives: Application of
compositional data analysis for the segregation of their cultivars and production
areas.
AB - The work presents the application of compositional data methodology to analytical
results, taking as an example the study of the volatile profiles of green Spanish
style table olives according to cultivars and production areas. For this purpose,
the volatile compounds (analysed by GC-MS and expressed as percentages of the
total area) were considered as a compositional data set in the Simplex space and,
as a result, analysed by their specific new statistical tools. Application of
compositional exploratory tools (variation array, tertiary graphs, biplots, or
coda-dendrogram) allowed differentiating cultivars and production areas based on
their volatile profiles. Also, the application of Cluster and Principal Component
analysis to the ilr transformed values (coordinates), following the new
methodology, led to more realistic results than the formally incorrect
implementation of the standard multivariate analysis (developed for data from the
Euclidean space) to percentages (data in the Simplex). Therefore, the work
presents a novel consideration of the volatile profiles of table olives as
compositional data and shows their proper analysis by statistical tools
specifically developed for them.
PMID- 28411826
TI - A novel fluorescent biosensor for Adenosine Triphosphate detection based on the
polydopamine nanospheres integrating with enzymatic recycling amplification.
AB - Based on the protective performance of polydopamine nanospheres (PDANSs) for DNA
against nuclease digestion and the specific recognition characteristic of
aptamer, we have developed an enzymatic recycling signal amplification method for
highly sensitive and selective detection of adenosine triphosphate (ATP).
Fluorescence measurements were carried out to verify the DNA polymerase and
exonuclease III (Exo III) assisted target recycling process and fluorescence
signal amplification. In the absence of the ATP, initially, the signal DNA-PDANSs
complex was in the "off" state due to the efficient fluorescence quenching of 6
carboxyfluorescein (FAM) adjacent to the surface of PDANSs. Due to the binding of
the aptamer by ATP, it trigger DNA polymerase and Exo III assisted target
recycling process by the product of release, the complex would change into the
"on" state as a result of the dissociation of the FAM from the surface of PDANSs,
thus providing greatly enhanced fluorescence emission intensity. The method
allows quantitative detection of ATP in the range of 20-600nM with a detection
limit of 8.32nM. This biosensor requires no complex operations, and is a new high
efficiency method for ATP detection.
PMID- 28411827
TI - Sensitive determination of malondialdehyde in exhaled breath condensate and
biological fluids by capillary electrophoresis with laser induced fluorescence
detection.
AB - In this work, a sensitive capillary electrophoresis method with laser induced
fluorescence detection for determination of malondialdehyde in various biological
fluids was developed. Malondialdehyde reacts with thiobarbituric acid under
optimized conditions of pH=2, reaction time of 60min and temperature of 90
degrees C, yielding an adduct that can be separated in a 50mM sodium borate
background electrolyte at pH 9. The separation of the formed adduct was
accomplished in less than 6min with limit of detection of 1.1nM due to the use of
532nm laser module, exactly matching the maximum excitation wavelength of the
formed adduct. The developed method offers unprecedented sensitivity and was for
the first time used for analysis of malondialdehyde in exhaled breath condensate.
The method proved to be also applicable to other samples of biological fluids,
such as blood plasma and saliva.
PMID- 28411828
TI - Development of reusable magnetic chitosan microspheres adsorbent for selective
extraction of trace level silver nanoparticles in environmental waters prior to
ICP-MS analysis.
AB - Solid-phase extraction (SPE) based on reusable magnetic chitosan microspheres was
coupled with ICP-MS for separation and quantification of silver nanoparticles
(AgNPs) in the presence of silver ions in environmental water samples. The
monodisperse magnetic chitosan microspheres with an average size of 2um were
engineered using suspension cross-linking technique, and characterized and
investigated for its application as SPE adsorbent. Parameters affecting the SPE
were optimized, and the best performance was achieved by extracting a 20mL sample
(pH 4.5) with 10mg adsorbent for 90min, followed by elution with 1mL 1% (w/v)
thiourea in 10% (v/v) nitric acid for 10min. The detection limit, calculated as
3s (s, standard deviation for 11 blank readings), for three AgNPs coated with
polyvinyl pyrrolidone (PVP), citrate and polyvinyl alcohol (PVA) and sizes of 31,
40, 46nm, respectively, were in the range of 0.016-0.023MUg/L. The repeatability
and reproducibility (RSD, n=7) at a spiking level of 0.1MUg/L AgNPs were 4.2% and
8.1%, respectively. The developed method has been applied in the analysis of
AgNPs in river, lake and wastewater samples, with excellent extraction
efficiencies (84.9-98.8%) for AgNPs at spiking levels of 0.86 and 8.70MUg/L. The
cationic chitosan microspheres showed good species selectivity and reusability
for extraction of AgNPs in the presence of Ag+, and hence the proposed method is
simple, cost effective and environmentally friendly.
PMID- 28411829
TI - Rapid and efficient separation of glycoprotein using pH double-responsive
imprinted magnetic microsphere.
AB - As biomarkers of many diseases, glycoproteins are of great significance to
clinical diagnostics. However, the determination of low abundant glycoproteins in
complex biological samples without any pretreatment process is still a problem.
In this study, a rapid and convenient separation method for highly efficient
enrichment of glycoproteins is reported, based on pH double-responsive imprinted
magnetic microspheres. Thin imprinted polymer shells were fabricated onto the
surface of magnetic microspheres by free radical polymerization, using 2
(Dimethylamino) ethyl methacrylate as pH-sensitive monomer, 4-vinylphenylbronic
acid as boronate affinity monomer, and ovalbumin (OVA) as template molecule.
Combining the advantages of pH-sensitive monomer and boronate affinity monomer,
rapidly capture-release of OVA could be modulated by changing solution pH.
Moreover, high absorption ability (81.2mg/g) was achieved within about 10min.
This study provided responsible way to imprint glycoproteins and showed great
potential for glycoprotein detection in clinical diagnostic.
PMID- 28411830
TI - Leveraging Molecular Data Analysis to Understand Drug Response in Systemic
Sclerosis.
AB - Taroni et al. integrate and analyze genomic information generated from different
clinical trials on systemic sclerosis, a disease for which there is yet no Food
and Drug Administration-approved therapy. By using a recent network analysis
approach based on tissue-specific functionality, they leverage the biological
information extracted from molecular profiling studies and report findings that
could be useful for patient stratification.
PMID- 28411831
TI - Toxic Memories in Systemic Sclerosis.
AB - Systemic sclerosis is an autoimmune disease characterized by T-cell infiltration
in the skin that leads to fibrosis, which can be life-limiting. Although T cells
are important, it is not known which types mediate the fibrosis. The work
presented by Li et al shows that memory CD8+ cytotoxic T cells mediate fibrosis
via the secretion of IL-13. IL-13 is profibrotic, and it is released in a higher
amount in patients with systemic sclerosis. This suggests that targeting IL-13
may be therapeutically beneficial.
PMID- 28411832
TI - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Associations, Outcomes,
and Pathobiology-Thirty Years of Progress but Still Much to Be Done.
AB - Although rare, Stevens-Johnson syndrome and toxic epidermal necrolysis remain
among the most devastating of acute conditions involving the skin. In the past 30
years, tremendous progress has been made in understanding the causes and
pathobiology of this often life-threatening condition. Su et al demonstrate
associations between IL 15 serum levels and the outcome of patients with Stevens
Johnson syndrome and toxic epidermal necrolysis. Their findings provide ideas for
further investigations that may help us better understand the role of cytokines
in this T-cell mediate disease and provides clues to possible new therapies.
PMID- 28411833
TI - Atopic Dermatitis and Comorbidities: Added Value of Comprehensive
Dermatoepidemiology.
AB - Atopic dermatitis is common and in its severe form is devastating. This chronic
inflammatory dermatosis is part of the atopic syndrome, which includes asthma,
food allergies, and hay fever and is known to be associated with mental health
disorders. In line with psoriasis, several recent observational studies using
national survey and linkage data have suggested a link between atopic dermatitis
and cardiovascular disease. The atopic dermatitis field can benefit from the past
experiences in psoriasis research and should not follow the same path, but,
rather, aim for a more comprehensive approach from the beginning. A recent German
consortium studying links between atopic dermatitis and cardiovascular disease
first screened a large claims database, followed by analyses of more deeply
phenotyped (birth) cohorts with longitudinal data. In addition, genetic and
metabolic analyses assessing the predisposition of patients with atopic
dermatitis for cardiovascular disease were performed. Overall, the association
between atopic dermatitis and cardiovascular disease was at most modest, but in
more refined cohorts the cardiovascular risk profile and genetic architecture was
comparable. A more integrated approach could create clarity about the clinical
relevance of cardiovascular disease in individuals with atopic dermatitis sooner,
avoid speculation that affects patient care, and save scientific resources.
PMID- 28411834
TI - Glucocorticoids Inhibit Wound Healing: Novel Mechanism of Action.
AB - Jozic et al. describe mechanisms of glucocorticoid (GC) downregulation of wound
healing by interaction with the membrane bound GC receptor, followed by
stimulation of beta-catenin and c-myc pathways. Targeting the membrane bound GC
receptor or the recently discovered interaction of GC with mineralocorticoid
receptors may counteract negative effects of GC on the skin barrier and
potentially could serve as a remedy for age-related skin atrophy.
PMID- 28411835
TI - Erratum.
PMID- 28411836
TI - The JID in Full Flower.
PMID- 28411837
TI - Doing Good Research Is Difficult, Doing No Research Is More Difficult.
PMID- 28411838
TI - Introduction to JID's Landmarks in the Molecular Revolution.
PMID- 28411839
TI - The Molecular Revolution in Cutaneous Biology: EDC and Locus Control.
AB - The epidermal differentiation complex (EDC) locus consists of a cluster of genes
important for the terminal differentiation of the epidermis. While early studies
identified the functional importance of individual EDC genes, the recognition of
the EDC genes as a cluster with its shared biology, homology, and physical
linkage was pivotal to later studies that investigated the transcriptional
regulation of the locus. Evolutionary conservation of the EDC and the
transcriptional activation during epidermal differentiation suggested a cis
regulatory mechanism via conserved noncoding elements or enhancers. This line of
pursuit led to the identification of CNE 923, an epidermal-specific enhancer that
was found to mediate chromatin remodeling of the EDC in an AP-1 dependent manner.
These genomic studies, as well as the advent of high-throughput sequencing and
genome engineering techniques, have paved the way for future investigation into
enhancer-mediated regulatory networks in cutaneous biology.
PMID- 28411840
TI - The Molecular Revolution in Cutaneous Biology: Noncoding RNAs: New Molecular
Players in Dermatology and Cutaneous Biology.
AB - Progress in genome sequencing achieved during the last two decades revealed that
only about 2% of the genome codes for proteins, while the largest genome fraction
is encoding thousands of non-coding RNAs. Non-coding RNAs play indispensable
roles in regulating the activity and stability of the genome. Recent research in
the area of the non-coding transcriptome signified the crucial roles for RNA
regulatory networks in the normal development and their implications in a variety
of pathological conditions. Here, recent advances in our understanding of non
coding RNA-mediated regulation of skin development and homeostasis are
highlighted, focusing mainly on the regulatory roles of miRNAs and lncRNAs.
PMID- 28411842
TI - The Molecular Revolution in Cutaneous Biology: Investigating the Skin Microbiome.
AB - Building upon the knowledge garnered from investigations utilizing traditional
culturing methods, advances in sequencing technologies have catalyzed a
revolution in studying human-associated microbes: bacteria, fungi and viruses.
Skin microbiome research in healthy individuals and patients with dermatologic
disorders has provided insights into the complexity and biogeography of human
skin microbes. The continual developments in sequencing and analyses will provide
increasingly sophisticated tools to interrogate human-associated microbes,
ultimately to improve our understanding of health and disease.
PMID- 28411841
TI - The Molecular Revolution in Cutaneous Biology: The Era of Genome-Wide Association
Studies and Statistical, Big Data, and Computational Topics.
AB - The investigation of biological systems involving all organs of the body
including the skin is in era of big data. This requires heavy-duty computational
tools, and novel statistical methods. Microarrays have allowed the interrogation
of thousands of common genetic markers in thousands of individuals from the same
population (termed genome wide association studies or GWAS) to reveal common
variation associated with disease or phenotype. These markers are usually single
nucleotide polymorphisms (SNPs) that are relatively common in the population. In
the case of dermatological diseases such as alopecia areata, vitiligo, psoriasis
and atopic dermatitis, common variants have been identified that are associated
with disease, and these provide insights into biological pathways and reveal
possible novel drug targets. Other skin phenotypes such as acne, color and skin
cancers are also being investigated with GWAS. Analyses of such large GWAS
datasets require a consideration of a number of statistical issues including the
testing of multiple markers, population substructure, and ultimately a
requirement for replication. There are also issues regarding the missing
heritability of disease that cannot be entirely explained with current GWAS
approaches. Next generation sequencing technologies such as exome and genome
sequencing of similar patient cohorts will reveal additional variants
contributing to disease susceptibility. However, the data generated with these
approaches will be orders of magnitude greater than that those generated with
arrays, with concomitant challenges in the identification of disease causing
variants.
PMID- 28411843
TI - The Molecular Revolution in Cutaneous Biology: Emerging Landscape in Genomic
Dermatology: New Mechanistic Ideas, Gene Editing, and Therapeutic Breakthroughs.
AB - Stunning technological advances in genomics have led to spectacular breakthroughs
in the understanding of the underlying defects, biological pathways and
therapeutic targets of skin diseases leading to new therapeutic interventions.
Next-generation sequencing has revolutionized the identification of disease
causing genes and has a profound impact in deciphering gene and protein
signatures in rare and frequent skin diseases. Gene addition strategies have
shown efficacy in junctional EB and in recessive dystrophic EB (RDEB). TALENs and
Cripsr/Cas9 have emerged as highly efficient new tools to edit genomic sequences
to creat new models and to correct or disrupt mutated genes to treat human
diseases. Therapeutic approaches have not been limited to DNA modification and
strategies at the mRNA, protein and cellular levels have also emerged, some of
which have already proven clinical efficacy in RDEB. Improved understanding of
the pathogenesis of skin disorders has led to the development of specific drugs
or repurposing of existing medicines as in basal cell nevus syndrome, alopecia
areata, melanoma and EB simplex. These discoveries pave the way for improved
targeted personalized medicine for rare and frequent diseases. It is likely that
a growing number of orphan skin diseases will benefit from combinatory new
therapies in a near future.
PMID- 28411844
TI - Research Techniques Made Simple: Mass Cytometry Analysis Tools for Decrypting the
Complexity of Biological Systems.
AB - Mass cytometry by time-of-flight experiments allow analysis of over 40 functional
and phenotypic cellular markers simultaneously at the single-cell level. The data
dimensionality escalation accentuates limitations, inherent to manual analysis,
as being subjective, labor-intensive, slow, and often incapable of showing the
detailed features of each unique cell within populations. The subsequent
challenge of examining, visualizing, and presenting mass cytometry data has
motivated continuous development of dimensionality reduction methods. As a
result, an increasing recognition of the inherent diversity and complexity of
cellular networks is emerging, with the discovery of unexpected cell
subpopulations, hierarchies, and developmental pathways, such as those existing
within the immune system. Here, we briefly review some frequently used and
accessible mass cytometry data analysis tools, including principal component
analysis (PCA); spanning-tree progression analysis of density-normalized events
(SPADE); t-distributed stochastic neighbor embedding (t-SNE)-based visualization
(viSNE); automatic classification of cellular expression by nonlinear stochastic
embedding (ACCENSE); and cluster identification, characterization, and regression
(CITRUS). Mass cytometry, used together with these innovative analytic tools, has
the power to lead to key discoveries in investigative dermatology, including but
not limited to identifying signaling phenotypes with predictive value for early
diagnosis, prognosis, or relapse and a thorough characterization of intratumor
heterogeneity and disease-resistant cell populations, that may ultimately unveil
novel therapeutic approaches.
PMID- 28411847
TI - The Molecular Revolution in Cutaneous Biology: Era of Cytogenetics and Copy
Number Analysis.
AB - Development of karyotyping techniques in the 1950s sparked groundbreaking reports
of chromosomal aberrations in cancer, such as the Philadelphia chromosome in
chronic myelogenous leukemia in 1960, followed by a number of others. Spatial
resolution of karyotyping is limited and vital tumor cells are required for
metaphase preparation. To overcome these limitations, DNA hybridization
techniques were developed. In situ hybridization of radioactively or fluorescence
labeled RNA probes onto tumor samples allowed the identification of specific
genomic regions, translocations and copy number alterations. However, it is only
suited for a limited number of candidate genes or regions. Genome-wide copy
number analysis was made possible by the development of comparative genomic
hybridization. It compares an entire cancer genome to a normal genome by
differential fluorescence labeling and hybridization onto normal metaphase
chromosomes. Replacing the metaphase chromosomes with arrays of oligonucleotides
significantly increased the resolution. Karyotypic analysis of melanomas could
demonstrate chromosomal aberrations decades ago. However, only CGH allowed
understanding the complex melanoma genomes. Based on mutation analysis and CGH
data, Boris Bastian and his group changed our view of melanoma towards a variety
of genetically distinct tumors. Recent next generation sequencing allows
simultaneous mutation, translocation and copy number analysis, and thereby
accelerates melanoma research.
PMID- 28411848
TI - The Molecular Revolution in Cutaneous Biology: Identification of Skin Disease
Genes.
PMID- 28411850
TI - The Molecular Revolution in Cutaneous Biology: Era of Mosaicism.
PMID- 28411849
TI - The Molecular Revolution in Cutaneous Biology: Keratin Genes and their Associated
Disease: Diversity, Opportunities, and Challenges.
AB - The abundance of keratin proteins and the filaments they form in surface
epithelia has long been appreciated. This said, the remarkable diversity of
keratin proteins and the notion that they are encoded by one of the largest gene
families in the human genome has come to the fore relatively recently, coinciding
with the sequencing of whole genomes. This complexity has generated some
practical challenges, notably in terms of nomenclature and tractability. More
importantly, however, studies of keratin have seeded the discovery of the genetic
basis for a large number of genodermatoses and continue to provide a unique
perspective on and insight into epithelial cells and tissues, whether normal or
diseased.
PMID- 28411851
TI - The Molecular Revolution in Cutaneous Biology: Era of Next-Generation Sequencing.
AB - Like any true conceptual revolution, next-generation sequencing (NGS) has not
only radically changed research and clinical practice, it has also modified
scientific culture. With the possibility to investigate DNA contents of any
organism and in any context, including in somatic disorders or in tissues
carrying complex microbial populations, it initially seemed as if the genetic
underpinning of any biological phenomenon could now be deciphered in an almost
streamlined fashion. However, over the past recent years, we have once again come
to understand that there is no such a thing as great opportunities without great
challenges. The steadily expanding use of NGS and related applications is now
facing biologists and physicians with novel technological obstacles, analytical
hurdles and increasingly pressing ethical questions.
PMID- 28411852
TI - The Molecular Revolution in Cutaneous Biology: Era of Molecular Diagnostics for
Inherited Skin Diseases.
AB - The discovery of pathogenic mutations in inherited skin diseases represents one
of the major landmarks of late 20th century molecular genetics. Mutation data can
provide accurate diagnoses, improve genetic counseling, help define disease
mechanisms, establish disease models, and provide a basis for translational
research and testing of novel therapeutics. The process of detecting disease
mutations, however, has not always been straightforward. Traditional approaches
using genetic linkage or candidate gene analysis have often been limited, costly,
and slow to yield new insights, but the advent of next-generation sequencing
(NGS) technologies has altered the landscape of current gene discovery and
mutation detection approaches.
PMID- 28411853
TI - The Molecular Revolution in Cutaneous Biology: The Era of Global Transcriptional
Analysis.
AB - In the 3 decades since the discovery of the polymerase chain reaction, a
progression of remarkable technical advances has driven great strides in our
understanding of molecular biology such that now we are able to study at once the
entire and complete set of RNA transcripts that are produced by the genome. In
this review, we describe the milestones that have led to this era of global
transcriptional analysis, how these approaches have been extended towards skin
disease, and their future directions.
PMID- 28411855
TI - Single molecule force spectroscopy for in-situ probing oridonin inhibited ROS
mediated EGF-EGFR interactions in living KYSE-150 cells.
AB - As the active anticancer component of Rabdosia Rubescens, oridonin has been
proved to show strong anticancer activity in cancer cells, which is also found to
be closely related to its specific inhibition effects on the EGFR tyrosine kinase
activity. In this study, atomic force microscopy based single molecule force
spectroscopy (AFM-SMFS) was used for real-time and in-situ detection of EGF-EGFR
interactions in living esophageal cancer KYSE-150 cells to evaluate the
anticancer activity of oridonin for the first time. Oridonin was found to induce
apoptosis and also reduce EGFR expression in KYSE-150 cells. AFM-SMFS results
demonstrated that oridonin could inhibit the binding between EGF and EGFR in KYSE
150 cells by decreasing the unbinding force and binding probability for EGF-EGFR
complexes, which was further proved to be closely associated with the
intracellular ROS level. More precise mechanism studies based on AFM-SMFS
demonstrated that oridonin treatment could decrease the energy barrier width,
increase the dissociation off rate constant and decrease the activation energy of
EGF-EGFR complexes in ROS dependent way, suggesting oridonin as a strong
anticancer agent targeting EGF-EGFR interactions in cancer cells through ROS
dependent mechanism. Our results not only suggested oridonin as a strong
anticancer agent targeting EGF-EGFR interactions in ROS dependent mechanism, but
also highlighted AFM-SMFS as a powerful technique for pharmacodynamic studies by
detecting ligand-receptor interactions, which was also expected to be developed
into a promising tool for the screening and mechanism studies of drugs.
PMID- 28411856
TI - Corrigendum to "Hexanal as biomarker for milk oxidative stress induced by copper
ions" (J. Dairy Sci. 100:1650-1656).
PMID- 28411857
TI - Corrigendum to "Health, physiology, and behavior of dairy calves reared on 4
different substrates" (J. Dairy Sci. 100:2148-2156).
PMID- 28411854
TI - The Molecular Revolution in Cutaneous Biology: Chromosomal Territories, Higher
Order Chromatin Remodeling, and the Control of Gene Expression in Keratinocytes.
AB - Three-dimensional organization of transcription in the nucleus and mechanisms
controlling the global chromatin folding, including spatial interactions between
the genes, noncoding genome elements, and epigenetic and transcription machinery,
are essential for establishing lineage-specific gene expression programs during
cell differentiation. Spatial chromatin interactions in the nucleus involving
gene promoters and distal regulatory elements are currently considered major
forces that drive cell differentiation and genome evolution in general, and such
interactions are substantially reorganized during many pathological conditions.
During terminal differentiation of the epidermal keratinocytes, the nucleus
undergoes programmed transformation from highly active status, associated with
execution of the genetic program of epidermal barrier formation, to a fully
inactive condition and finally becomes a part of the keratinized cells of the
cornified epidermal layer. This transition is accompanied by marked remodeling of
the three-dimensional nuclear organization and microanatomy, including changes in
the spatial arrangement of lineage-specific genes, nuclear bodies, and
heterochromatin. This mini-review highlights the important landmarks in the
accumulation of our current knowledge on three-dimensional organization of the
nucleus, spatial arrangement of the genes, and their distal regulatory elements,
and it provides an update on the mechanisms that control higher-order chromatin
remodeling in the context of epidermal keratinocyte differentiation in the skin.
PMID- 28411858
TI - Corrigendum to "Different milk feeding intensities during the first 4 weeks of
rearing dairy calves: Part 2: Effects on the metabolic and endocrine status
during calfhood and around the first lactation" (J. Dairy Sci. 100:3109-3125).
PMID- 28411860
TI - Importance of Accommodation and Eye Dominance for Measuring Objective
Refractions.
PMID- 28411859
TI - CD14 Plays a Protective Role in Experimental Inflammatory Bowel Disease by
Enhancing Intestinal Barrier Function.
AB - Intestinal homeostasis disturbance through intestinal barrier disruption
presumably plays a key role in inflammatory bowel disease (IBD) development.
Genetic and candidate gene analyses in an Il10-deficient IBD mouse model system
identified Cd14 as a potentially protective candidate gene. The role of Cd14 in
colitis development was determined using dextran sulfate sodium (DSS)-induced
acute and an Il10-deficiency-induced chronic model of intestinal inflammation.
Intestinal permeability was investigated by fluorescein isothiocyanate-dextran
uptake assay, quantitative RT-PCR analysis of tight junction proteins, myosin
light chain kinase, and proinflammatory cytokine expression. Immunohistological
staining of occludin, Ki-67, NF-kappaB-p65, and terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling assay was performed, and intestinal
inflammation severity was evaluated histologically. Untreated B6-Cd14-/- mice and
wild-type controls did not differ in intestinal barrier function. However, DSS
treated Cd14-deficient and B6-Il10-/-Cd14-/- mice exhibited more severe
intestinal barrier disruption, with increased histological scores and
proinflammatory cytokine expression, compared to controls. Therefore, Cd14
deficiency did not influence epithelial integrity under steady-state conditions
but caused intestinal barrier dysfunction under inflammation. As expected, CD14
overexpression increased barrier integrity. No difference in intestinal
epithelial NF-kappaB translocation was observed between the investigated groups.
Intestinal myosin light chain kinase expression decreased in Cd14-deficient mice
under steady-state conditions and in the chronic model, whereas no difference was
detected in the DSS models. Thus, CD14 plays a protective role in IBD development
by enhancing intestinal barrier function.
PMID- 28411861
TI - Reply.
PMID- 28411862
TI - Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With
Pseudomonas aeruginosa and Fusarium spp.
AB - Photodynamic therapy (PDT) is a therapeutic modality with significant
antimicrobial activity. We present 2 cases of chronic lower limb ulcers in which
fungal and bacterial superinfection complicated management. PDT with methylene
blue as the photosensitizer led to clinical and microbiological cure with no
significant adverse effects. PDT with methylene blue is a valid option for the
management of superinfected chronic ulcers, reducing the use of antibiotics and
the induction of resistance.
PMID- 28411863
TI - Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?
AB - OBJECTIVE: There is currently no consensus regarding how to address pelvic
sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify
the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a
prospectively collected multi-institutional melanoma database. RESULTS: Of 2476
cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to
both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and
46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal
metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and
SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14%
respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy
upstaged one patient (0.6%), and completion dissection based on a positive PSLN
did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of
negative SSLNs there is minimal clinical impact. We therefore recommend PSLN
biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.
PMID- 28411864
TI - Extended anticoagulation in venous thromboembolism disease. In favour.
AB - Venous thromboembolism disease can be considered a chronic disease because, after
the first episode, there is a life-long risk of recurrence. Recurrence is a
severe complication. Anticoagulation is effective while it is maintained, but
when it is discontinued, the risk of new thrombotic events persists indefinitely.
Clinical practice guidelines offer specific recommendations on the treatment
duration for patients with provoked or recurrent disease but are not specific for
those with a first unprovoked episode. The decision should be made after a
careful individual assessment of the risk-benefit of anticoagulation. This
article reviews the evidence in favour of extending the anticoagulation and the
current therapeutic options.
PMID- 28411865
TI - Predicting postoperative outcomes of liver resection by magnetic resonance
elastography.
AB - BACKGROUND: Cirrhosis is associated with blood loss during liver resection and
postoperative complications. The liver stiffness measurement has recently become
available for assessment of liver fibrosis. METHODS: This prospective study was
performed to predict postoperative outcomes of liver resection. The liver
stiffness measurement was measured prospectively using magnetic resonance
elastography for patients who had undergone liver resection for malignancy. We
investigated whether the liver stiffness measurement by magnetic resonance
elastography is correlated with liver fibrosis and postoperative outcomes.
RESULTS: The median liver stiffness measurement by magnetic resonance
elastography in 175 patients was 3.4 (range: 1.5-11.3) kPa, and the pathologic
grade of liver fibrosis was significantly correlated with the liver stiffness
measurement (r = 0.68, P < .001). The median blood loss during transection per
unit area was 4.1 mL/cm2 (range: 0.1-37.0 mL/cm2), and the frequency of major
complications was 16.0%. The liver stiffness measurement was the only independent
prognostic factor for both blood loss (regression coefficient: 1.14, 95%
confidence interval: 0.45-1.83, P = .001) and major complications (odds ratio:
2.14, 95% confidence interval: 1.63-2.93, P < .001). Receiver operating
characteristic curve analysis indicated a significant correlation between the
liver stiffness measurement and major complications with calculated area under
the curve of 0.81 (P < .001), and the sensitivity and specificity for prediction
of major complications (cutoff value: 5.3 kPa) were 64.3% and 87.8%,
respectively. On the other hand, the amount of blood loss was significantly
correlated with the frequency of major complications (P = .003). CONCLUSION: The
liver stiffness measurement by magnetic resonance elastography could be used as a
predictive marker for the risk of major complications due to blood loss during
liver resection.
PMID- 28411866
TI - Addressing the challenges of sleeve gastrectomy in end-stage renal disease:
Analysis of 100 consecutive renal failure patients.
AB - BACKGROUND: While previous studies have demonstrated short-term efficacy of
laparoscopic sleeve gastrectomy in candidates awaiting renal transplantation, the
combination of morbid obesity and end-stage renal disease presents unique
challenges to perioperative care. We demonstrate how increasing experience and
the development of postoperative care guidelines can improve outcomes in this
high-risk population. METHODS: Single-center medical records were reviewed for
renal transplantation candidates undergoing laparoscopic sleeve gastrectomy
between 2011 and 2015 by a single surgeon. Postoperative care protocols were
established and continually refined throughout the study period, including a
multidisciplinary approach to inpatient management and hospital discharge
planning. The first 100 laparoscopic sleeve gastrectomy patients were included
and divided into 4 equal cohorts based on case sequence. RESULTS: Compared with
the first 25 patients undergoing laparoscopic sleeve gastrectomy, the last 25
patients had shorter operative times (97.8 +/- 27.9 min vs 124.2 +/- 33.6 min),
lower estimated blood loss (6.6 +/- 20.8 mL vs 34.0 +/- 38.1 mL), and shorter
hospital duration of stay (1.7 +/- 2.1 days vs 2.9 +/- 0.7 days) (P < .01 each).
Readmission rates, complications, and 1-year mortality did not differ
significantly. CONCLUSION: Increasing experience and the development of clinical
care guidelines in this high-risk population is associated with reduced health
care resource utilization and improved perioperative outcomes.
PMID- 28411867
TI - A rapid approach for measuring silver nanoparticle concentration and dissolution
in seawater by UV-Vis.
AB - Detection and quantification of engineered nanoparticles (NPs) in environmental
systems is challenging and requires sophisticated analytical equipment.
Furthermore, dissolution is an important environmental transformation process for
silver nanoparticles (AgNPs) which affects the size, speciation and concentration
of AgNPs in natural water systems. Herein, we present a simple approach for the
detection, quantification and measurement of dissolution of PVP-coated AgNPs (PVP
AgNPs) based on monitoring their optical properties (extinction spectra) using UV
vis spectroscopy. The dependence of PVP-AgNPs extinction coefficient (E) and
maximum absorbance wavelength (lambdamax) on NP size was experimentally
determined. The concentration, size, and extinction spectra of PVP-AgNPs were
characterized during dissolution in 30ppt synthetic seawater. AgNPs concentration
was determined as the difference between the total and dissolved Ag
concentrations measured by inductively coupled plasma-mass spectroscopy (ICP-MS);
extinction spectra of PVP-AgNPs were monitored by UV-vis; and size evolution was
monitored by atomic force microscopy (AFM) over a period of 96h. Empirical
equations for the dependence of maximum absorbance wavelength (lambdamax) and
extinction coefficient (E) on NP size were derived. These empirical formulas were
then used to calculate the size and concentration of PVP-AgNPs, and dissolved Ag
concentration released from PVP-AgNPs in synthetic seawater at variable particle
concentrations (i.e. 25-1500MUgL-1) and in natural seawater at particle
concentration of 100MUgL-1. These results suggest that UV-vis can be used as an
easy and quick approach for detection and quantification (size and concentration)
of sterically stabilized PVP-AgNPs from their extinction spectra. This approach
can also be used to monitor the release of Ag from PVP-AgNPs and the concurrent
NP size change. Finally, in seawater, AgNPs dissolve faster and to a higher
extent with the decrease in NP concentration toward environmentally relevant
concentrations.
PMID- 28411868
TI - High resolution stream water quality assessment in the Vancouver, British
Columbia region: a citizen science study.
AB - Changing land cover and climate regimes modify water quantity and quality in
natural stream systems. In regions undergoing rapid change, it is difficult to
effectively monitor and quantify these impacts at local to regional scales. In
Vancouver, British Columbia, one of the most rapidly urbanizing areas in Canada,
750 measurements were taken from a total of 81 unique sampling sites representing
49 streams located in urban, forest, and agricultural-dominant watersheds at a
frequency of up to 12 times per year between 2013 and 2016. Dissolved nitrate
(NO3-N) and phosphate (PO4-P) concentrations, turbidity, water temperature, pH
and conductivity were measured by citizen scientists in addition to observations
of hydrology, vegetation, land use, and visible stream impacts. Land cover was
mapped at a 15-m resolution using Landsat 8 OLI imagery and used to determine
dominant land cover for each watershed in which a sample was recorded. Regional,
seasonal, and catchment-type trends in measurements were determined using
statistical analyses. The relationships of nutrients to land cover varied
seasonally and on a catchment-type basis. Nitrate showed seasonal highs in winter
and lows in summer, though phosphate had less seasonal variation. Overall,
nitrate concentrations were positively associated to agriculture and deciduous
forest and negatively associated with coniferous forest. In contrast, phosphate
concentrations were positively associated with agricultural, deciduous forest,
and disturbed land cover and negatively associated with urban land cover. Both
urban and agricultural land cover were significantly associated with an increase
in water conductivity. Increased forest land cover was associated with better
water quality, including lower turbidity, conductivity, and water temperature.
This study showed the importance of high resolution sampling in understanding
seasonal and spatial dynamics of stream water quality, made possible with the
large number of measurements taken with the help of trained volunteers. The
results underscore the value of citizen science in freshwater research.
PMID- 28411870
TI - The presence of coronary artery lesions may indicate the severity of the
inflammation rather than the cause.
PMID- 28411869
TI - Detection of endocrine disrupting chemicals and evidence of their effects on the
HPG axis of the European anchovy Engraulis encrasicolus.
AB - Natural/synthetic Endocrine Disrupting Chemicals (EDCs) may display estrogenic
activity and a lower potency than 17beta-estradiol. Nonetheless, their
concentrations and additive effects can affect the endocrine system and
reproductive processes related to the Hypothalamic-Pituitary-Gonadal (HPG) axis.
Because of their persistence in both the environment and biological systems, they
ultimately target multi-level predators, including humans. We detected presence
and effects of xenobiotics on wild anchovy Engraulis encrasicolus in the Western
Adriatic Sea. Twenty-one PCBs and five organochlorines were detected on the order
of ng g-1; vitellogenin, vitellogenin receptor and genes encoding for the zona
radiata proteins were evaluated in gonad and/or liver and found transcribed in
male specimens; in addition, intersex was histologically identified in the 13% of
testis. Our results have developed the understanding of the European anchovy's
reproductive toxicological risk and our approach could assist the comprehension
of the complex dynamics of commercially relevant Teleost species.
PMID- 28411871
TI - Targeting interleukin 23 for Crohn's disease: finding the right drug for the
right patient.
PMID- 28411872
TI - Induction therapy with the selective interleukin-23 inhibitor risankizumab in
patients with moderate-to-severe Crohn's disease: a randomised, double-blind,
placebo-controlled phase 2 study.
AB - BACKGROUND: The interleukin-23 pathway is implicated genetically and biologically
in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and
safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a
humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in
patients with moderately-to-severely active Crohn's disease. METHODS: In this
randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients
at 36 referral sites in North America, Europe, and southeast Asia. Eligible
patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least
3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as
a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the
ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity
(CDEIS) of at least 7 (>=4 for patients with isolated ileitis) on ileocolonoscopy
scored by a masked central reader. Patients were randomised 1:1:1 using an
interactive response system to a double-blind investigational product, and
stratified by previous exposure to TNF antagonists (yes vs no). Patients received
intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4,
and 8. The primary outcome was clinical remission (CDAI <150) at week 12
(intention-to-treat population). Safety was assessed in patients who received at
least one dose of study drug. This study is registered with ClinicalTrials.gov,
number NCT02031276. FINDINGS: Between March, 2014, and September, 2015, 213
patients were screened, and 121 patients randomised. At baseline, 113 patients
(93%) had been previously treated with at least one tumour necrosis factor (TNF)
antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82
risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg
arms) had clinical remission versus six (15%) of 39 placebo patients (difference
vs placebo 15.0%, 95% CI 0.1 to 30.1; p=0.0489). Ten (24%) of 41 patients who
received 200 mg risankizumab had clinical remission (9.0%, -8.3 to 26.2; p=0.31)
and 15 (37%) of 41 who received the 600 mg dose (20.9%, 2.6 to 39.2; p=0.0252).
95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to
200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse
events (nine, six, three); 12 discontinued (six, five, one); 24 had serious
adverse events (12, nine, three). The most common adverse event was nausea and
most common serious adverse event was worsening of underlying Crohn's disease. No
deaths occurred. INTERPRETATION: In this short-term study, risankizumab was more
effective than placebo for inducing clinical remission in patients with active
Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition
of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING:
Boehringer Ingelheim.
PMID- 28411873
TI - [Survey adaptation for bio-behavioural surveillance of HIV in Chilean female sex
workers].
AB - OBJECTIVE: To adapt a behavioural questionnaire for second-generation HIV/AIDS
surveillance in female sex workers (FSWs) in the Metropolitan Region, Chile.
METHODS: Qualitative study of instruments validation. A Spanish instrument
adapted in Catalonia was validated through a translation and back-translation of
the original version. The content validity was determined through a modified
Delphi method, via FSW and HIV experts representing community, political and
institutional levels. Applicability aspects were determined by the application of
the questionnaire to FSW in the Metropolitan Region. RESULTS: The questionnaire,
drafted in Spain, was successfully adapted to Chilean Spanish. The content
validity process enabled sections to be created that address HIV in FSWs. The
adapted questionnaire takes less than 15minutes to complete, which makes it
usable in fieldwork. The 61 women surveyed came from different countries (all
were Latin Americans) and had different educational levels; all this enabled
potential applicability problems to be detected. DISCUSSION: The adapted
questionnaire for Chile contains all the UNAIDS indicators for FSWs, as well as
the recommended indicators of Family Health International for bio-behavioural
surveillance. Said questionnaire serves as a tool for second-generation HIV/other
STD surveillance and further contributes to preventive policies in Chilean FSWs.
PMID- 28411874
TI - [Association between radiation from mobile phones and tumour risk in adults].
AB - OBJECTIVE: To synthesize and analyse systematic reviews, case-control studies,
cohort studies and meta-analysis that investigate the association between
exposure to radiofrequency from mobile phones and the appearance of tumours in
adults. METHODS: A systematic search was conducted in Scopus, Web of Science, The
Cochrane Library, Medline and Cinahl of articles published in English and Spanish
between January 2005 and February 2016 that analyse the risk of tumour associated
with exposure to radiofrequency from mobile phones in adults. The recommendations
of the PRISMA Declaration were followed, and the quality of the articles was
analysed with the AMSTAR tool and the Newcastle-Ottawa Scale. RESULTS: 1034
studies were found, fourteen of which were included. Most studies agree that it
is not possible to determine a relationship in the short term, although long-term
(over 10 years) radiofrequency emitted by mobile phones can cause tumour effects,
with an increased risk by ipsilateral exposure and latency. CONCLUSIONS: Although
radiofrequency from mobile phones has tumour effects on humans, the available
scientific evidence is not robust. More rigorous follow-up studies with larger
sample sizes and broader periods are necessary to learn more about the long-term
effects.
PMID- 28411875
TI - Association between lateral patellar osteoarthrosis and knee morphology and
alignment in young adults.
AB - AIM: To assess whether patellar and trochlea morphology and patellar alignment
are associated with lateral patellar osteoarthrosis/chondrosis (OAC) in young
adults. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) images of 183
subjects (81 cases, 102 controls) aged 21-35 years of age were evaluated.
Quantitative measurements of patella and trochlea morphology and patellar
alignment were obtained. Axial and sagittal MRI images were reviewed to grade the
severity of focal cartilage defects along the lateral facet of the patella.
Controls had knees without any abnormalities and were compared to cases with mild
and severe lateral patellar OAC. Multivariable logistic regression was used to
assess associations between measurements and lateral patellar OAC adjusting for
body mass index. RESULTS: Cases were more likely to have higher Insall-Salvati
ratios (OR=350; p<0.001), shorter ratios of the medial to lateral facets of the
patella (OR=1.63*10-3; p<0.001), a shallower (angle closer to 180 degrees )
median eminence of the patella (OR=1.063; p=0.009), decreased trochlear cartilage
overlap with the patellar cartilage (OR=0.086; p=0.023), and a less angulated
lateral patellofemoral angle (OR=0.903; p=0.028), compared to controls. Cases
were also more likely to have patellar tendinosis (OR=5.265; p=0.045) and oedema
in the superolateral aspect of Hoffa's fat pad (OR=9.872; p<0.001). CONCLUSION:
Patellar and trochlear morphology and patellar alignment are associated with
lateral patellofemoral compartment OAC in young adults.
PMID- 28411876
TI - Stakeholders' Perceptions of Care Coordination: A Participatory Process.
AB - OBJECTIVE: Children with special health care needs or chronic conditions are more
likely to have unmet health needs than other children. The purpose of this study
was to use a community engagement research strategy to assess the essential
elements of care coordination that can serve as the foundation for a system-wide
care coordination model for children with special health care needs. STUDY
DESIGN: As part of a summit designed to review the status of pediatric care
coordination within the state of Arizona and a call to action, a qualitative
descriptive study was conducted to solicit anonymous feedback from 104
stakeholders (family, health care provider, or community entity) on the strengths
and areas of improvement in the current system that provides care to Arizona
children with special health care needs. Data were analyzed using inductive
content analysis. RESULTS: Five essential categories crucial to building an
effective and seamless care coordination model were extracted from the data:
Communication, Insurance, Health Care Capacity, Provider Knowledge, and Family
Education. CONCLUSIONS: The results from this study can serve as the working
foundation to build a system-wide model for pediatric care coordination
throughout the state. Providing care coordination services involves many
activities across a wide range of organizations and locations. Research that is
inclusive of community stakeholders can determine essential components for
building a foundation for care coordination.
PMID- 28411877
TI - Combined resection and radiofrequency ablation versus transarterial embolization
for intermediate-stage hepatocellular carcinoma: A propensity score matching
study.
AB - BACKGROUND/PURPOSE: This study aimed to compare the outcomes of combined hepatic
resection (HR) plus intraoperative radiofrequency ablation (RFA) and
transarterial embolization (TAE) for Barcelona Clinic Liver Cancer (BCLC) stage B
hepatocellular carcinoma (HCC) in case-controlled patient groups using the
propensity score. METHODS: A total of 179 patients with multifocal HCC treated
with HR plus RFA (n = 26) or TAE (n = 153) were retrospectively studied. All
patients were classified as BCLC stage B and Child-Pugh class A. Analyses were
performed over all participants as well as for propensity score-matched (1:3)
patients to adjust for baseline differences. Cumulative overall survival (OS) and
time to progression (TTP) were compared between the two groups using the Kaplan
Meier method, and independent predictors were identified by multivariate Cox
regression analysis. RESULTS: Patients treated with HR plus RFA had better OS and
longer TTP than those with TAE (p = 0.011 and p < 0.001, respectively).
Multivariate Cox regression analysis showed that combined therapy (hazard ratio
0.31; 95% confidence interval (CI), 0.12-0.78; p = 0.013), BCLC substage B2
(hazard ratio 1.82; 95% CI, 1.13-2.92; p = 0.013) and alpha-fetoprotein >= 400
ng/ml (hazard ratio 1.85; 95% CI, 1.12-3.05; p = 0.016) were independent factors
associated with OS. After propensity score matching, combined therapy was the
significant factor associated with OS and TTP by univariate and multivariate
analyses. CONCLUSION: Combined HR plus RFA may provide survival advantage
compared to TAE in patients with BCLC stage B HCC.
PMID- 28411878
TI - Food for thought: Autophagy researcher wins 2016 Nobel Prize in Physiology or
Medicine.
AB - This special edition of the Biomedical Journal honors the awarding of the 2016
Nobel Prize in Physiology and Medicine to Yoshinori Ohsumi for his pioneering
work on elucidating the mechanisms of autophagy. We also highlight a study
reporting a new and simple animal model for a widespread surgical technique
called interbody spinal fusion. Finally, this issue also includes two articles
reporting protocols that could produce specific cell types for cell based
therapies.
PMID- 28411879
TI - Apicomplexan autophagy and modulation of autophagy in parasite-infected host
cells.
AB - Apicomplexan parasites are responsible for a number of important human
pathologies. Obviously, as Eukaryotes they share a number of cellular features
and pathways with their respective host cells. One of them is autophagy, a
process involved in the degradation of the cell's own components. These
intracellular parasites nonetheless seem to present a number of original features
compared to their very evolutionarily distant host cells. In mammals and other
metazoans, autophagy has been identified as an important contributor to the
defence against microbial pathogens. Thus, host autophagy also likely plays a key
role in the control of apicomplexan parasites, although its potential
manipulation and subversion by intracellular parasites creates a complex
interplay in the regulation of host and parasite autophagy. In this mini-review,
we summarise current knowledge on autophagy in both parasites and their host
cells, in the context of infection by three Apicomplexa: Plasmodium, Toxoplasma,
and Theileria.
PMID- 28411880
TI - In vitro induction effect of 1,25(OH)2D3 on differentiation of hair follicle stem
cell into keratinocyte.
AB - BACKGROUND: Stem cells are characterized by self-renewal and differentiation
capabilities. The bulge hair follicle stem cells (HFSCs) are able to convert to
epithelial components. The active metabolite of vitamin D, 1,25(OH)2D3, plays
important roles in this differentiation process. In the present study has found
that 1,25(OH)2D3 induces the HFSCs differentiation into keratinocyte. METHODS:
HFSCs are isolated from rat whiskers and cultivated in DMEM medium. To isolate
bulge stem cell population, flow cytometry and immunocytochemistry using K15,
CD34 and nestin biomarkers were performed. In order to accelerate the HFSCs
differentiation into eratinocyte, HFSCs were treated with 10-12 M, 1,25(OH)2D3
every 48 h for a week. RESULTS: Immunocytochemistry results showed that bulge
stem cells are nestin and CD34 positive but K15 negative before differentiation.
Subsequently flow cytometry results, showed that the expression of nestin, CD34
and K15 were 70.96%, 93.03% and 6.88% respectively. After differentiation, the
immunocytochemical and flow cytometry results indicated that differentiated cells
have positive reaction to K15 with 68.94% expression level. CONCLUSION: It was
concluded that 10-12 M, 1,25(OH)2D3 could induce the HFSCs differentiation into
keratinocytes.
PMID- 28411881
TI - Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed
prognostic implications for stage I-II colon cancer patients.
AB - BACKGROUND: The outcome of colon cancer patients without lymph node metastasis is
heterogeneous. Searching for new prognostic markers is warranted. METHODS: One
hundred twenty stage I-II colon cancer patients who received complete surgical
excision during 1995-2004 were selected for this biomarker study.
Immunohistochemical method was used to assess p53, epidermal growth factor
receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing.
RESULTS: Thirty three patients (27.5%) developed metachronous metastasis during
follow up. By multivariate analysis, only female gender (p = 0.03), high serum
carcinoembryonic antigen (CEA) level (?5 ng/ml) (p = 0.04), and MLH1
overexpression (p = 0.003) were associated with the metastasis group. The 5-year
survival rate were also significantly lower for female gender (71.7% versus
88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1
overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression
was associated with better survival, 95.1% versus 75.5% (p = 0.024). CONCLUSIONS:
The reversed prognostic implications in the overexpression of MLH1 and MSH2 for
stage I-II colon cancer patients is a novel finding and worthy of further
confirmation.
PMID- 28411882
TI - In-vitro generation of interleukin-10 secreting B-regulatory cells from donor
adipose tissue derived mesenchymal stem cells and recipient peripheral blood
mononuclear cells for potential cell therapy.
AB - BACKGROUND: Interleukin-10 secreting B-cells are a major subset of B-regulatory
cells (B-regs), commonly recognized as CD19+/38hi/24hi/IL10+. They carry out
immunomodulation by release of specific cytokines and/or cell-to-cell contact. We
have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem
cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear
cells (PBMC) for potential cell therapy. MATERIAL AND METHODS: Mononuclear cells
separated by density gradient centrifugation from 50 ml anti-coagulated blood of
15-RAR and respective donors were analysed for baseline B-regs using appropriate
antibodies. Equal amount (20 * 106 cells/ml) of stimulator (irradiated at 7.45
Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in
vitro generated AD-MSC (1 * 106 cells/ml) in proliferation medium containing
lipopolysaccharide from E. coli K12 strain at 37 degrees C with 5% CO2. Cells
were harvested on day-7 and analyzed for viability, sterility, quantity,
morphology and phenotyping. In-vitro generated B-reg levels were compared with
baseline B-regs. RESULTS: In-vitro generated B-reg count increased to 16.75% from
baseline count of 3.35%. CONCLUSION: B-regs can be successfully generated in
vitro from donor AD-MSC and RAR PBMC for potential cell therapy.
PMID- 28411883
TI - Horning cell self-digestion: Autophagy wins the 2016 Nobel Prize in Physiology or
Medicine.
AB - Autophagy is an evolutionarily conserved process by which eukaryotic cells
eliminate intracellular components via the lysosomal degradation process. This
cell self-digestion process was first discovered and morphologically
characterized in the late 1950s and early 1960s. The genetic screen studies in
baker's yeast in the 1990s further identified the essential genes functioning in
the autophagic process. In the past two decades, the detailed molecular process
involved in the completion of autophagy was delineated. Additionally, autophagy
has been implied to function in many aspects of biological processes, including
maintenance of organelle integrity, protein quality control, regulation of the
stress response, and immunity. In addition to maintain cell homeostasis,
autophagy has recently been shown to be modulated and to participate in the
pathogenesis of human diseases, such as pathogen infections, neurodegenerative
diseases, and tumor development. Overall, the breakthrough in autophagy research
relies on the discovery of autophagy-related genes (ATGs) using a genetic
screening approach in Saccharomyces cerevisiae, which was established by
Yoshinori Ohsumi. This year the Nobel Committee has awarded Yoshinori Ohsumi the
Nobel Prize in Physiology or Medicine for his remarkable contribution to
autophagy research.
PMID- 28411884
TI - Risk factors for relapse of resectable pathologic N2 non small lung cancer and
prediction model for time-to-progression.
AB - BACKGROUND: Pathologic N2 non-small-cell lung cancer (NSCLC) was demonstrated
with poor survival among literature. In this study, we retrospectively reviewed
patients with pathologic N2 NSCLC and received anatomic resection (i.e.
lobectomy) for further relapse risk factor analysis. The aim of this study is to
identify the clinicopathologic factors related to relapse among resectable N2
NSCLC patients and to help clinicians in developing individualized follow up
program and treatment plan. METHOD: From January 2005 to July 2012, 90 diagnosed
pathologic N2 NSCLC patients were enrolled into this study. We retrospectively
reviewed medical records, image studies, and pathology reports to collect the
patient clinico-pathologic factors. RESULT: We identified that patients with
visceral pleural invasion (p = 0.001) and skip metastases along mediastinal lymph
node (p = 0.01) had a significant relationship to distant and disseminated
metastases. Patients who had 2 or more risk factors for relapse demonstrated poor
disease free survival than those who had less than 2 risk factors (p = 0.02). The
number of involved metastatic area were significantly influential to the period
of time-to-progression. The duration of time-to-progression was correlated with
square of number of involved metastatic areas. (Pearson correlation coefficient =
-0.29; p = 0.036). CONCLUSION: Relapse risk factors of resectable pathologic N2
NSCLC patient after anatomic resection were visceral pleural invasion, skip
mediastinal lymph node involvement, and the receipt of neoadjuvant therapy. The
duration of time-to-progression was correlated with square of number of involved
metastatic areas.
PMID- 28411885
TI - Characterization of a novel caudal vertebral interbody fusion in a rat tail
model: An implication for future material and mechanical testing.
AB - BACKGROUND: Of the proposed animal interbody fusion models, rat caudal discs have
gained popularity in disc research due to their strong resemblance to human discs
with respect to geometry, composition and mechanical properties. The purpose of
this study is to demonstrate an efficient, repeatable and easily accessible
animal model of interbody fusion for future research into mechanical testing and
graft materials. METHODS: Twelve 12-week-old female Sprague-Dawley (SD) rats
underwent caudal interbody fusion of the third and fourth coccygeal vertebrae of
the tail. Serial radiological evaluation, and histological evaluation and manual
palpation after sacrifice were performed to assess the fusion quality. Mechanical
testing of functional units (FUs) of non-operated and operated segments was
compared using a three-point bending test. RESULTS: At postoperative 12 weeks,
callus formation was observed at the fusion sites in all rats, with the mean
radiological evaluations of 2.75/3 according to the Bransford classification.
Newly formed bone tissue was also observed in all rats with the mean histological
score of 5.85/7, according to the Emery grading system. No palpable gaps and
obvious change of bending stiffness was observed in the operated segments. The
mean bending stiffness of the FUs was statistically higher than that of the
control FUs (26.57 +/- 6.71 N/mm vs. 12.45 +/- 3.21 N/mm, p < 0.01). CONCLUSION:
The rat caudal disc interbody fusion model proved to be an efficient, repeatable
and easily accessible model. Future research into adjuvant treatments like growth
factor injection and alternative fusion materials under conditions of
osteoporosis using this model would be worthwhile.
PMID- 28411886
TI - Interference factors regarding the path of insertion of rotational-path removable
partial dentures.
AB - BACKGROUND: The aims of this study were to evaluate the effect of the location of
the rotational center and the morphology of teeth resulting in interference with
the rotational path of insertion and to estimate when an interference test should
be performed. METHODS: A total of 400 dental radiograms of maxillary and
mandibular first and second molars (100 for each position) were selected. The
radiograms were used to hand-sketch the outlines on tracing paper. Then, an
interference test was simulated using calipers. Mesial long occlusal rest seats
with three different lengths were designed. A curve-simulated rotational path was
drawn on the tracing paper showing the outline of a molar. If the curve was
intersected by the mesial outline, interference was occurred. A total of 1200
tests were performed. RESULTS: A significant number of interference cases (18.5%,
N = 400) occurred when the rotational center was placed at the most distal margin
of the occlusal surface. The interference was reduced (2.75%, N = 400) but still
present at the distal fourth of the occlusal surface. At the distal one-third of
the occlusal surface, interference did not occur (0%, N = 400). There was a
significant difference between the results of the three rotational centers (p <
0.0001). CONCLUSIONS: The interference test was not required for a rotational
center at the distal third to half of the occlusal surface. However, if the
length of the long occlusal rest extends beyond the distal third, an interference
test is recommended before final impression.
PMID- 28411889
TI - Factibility and security study of the PICS-AFTM plug for the treatment of
cryptoglandular anal fistula.
AB - INTRODUCTION: The PICS-AFTM (Curaseal Inc.) device is a new plug made of collagen
that has a retention system in the internal orifice. This pilot study was
designed to assess both the feasibility and safety of this plug in the treatment
of trans-sphincteric anal fistulas. METHODS: A total of 44 patients (34 men),
with a mean age of 54.68+/-7.3, with trans-sphincteric anal fistulas were
included in the study; 34 of them were analyzed. All patients were examined
according to a strict preoperative protocol and until 6 months after surgery. The
feasibility of the procedure and the adverse events were analyzed. RESULTS:
Finally, 34 patients were operated on, and in 30 of them the plug was used.
Therefore, the feasibility was calculated at 88%. There was a total of 16 adverse
events, 4recorded as not related (3 mild and one moderate) and 12 related to the
procedure or to the device implanted. Of these, 5were mild, 5moderate and
2severe. The majority of the events reported were related to proctalgia (4
patients) or infection at the implant site (4 patients). CONCLUSIONS: The present
study indicates that the new collagen plug can be placed effectively and with an
acceptable complication rate.
PMID- 28411888
TI - Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0
rectal tumors. Local recurrence, complete clinical and pathological response.
AB - INTRODUCTION: The association of preoperative chemoradiotherapy and transanal
endoscopic surgery in T2 and superficial T3 rectal cancers presents promising
results in selected patients. The main objective is to evaluate the long-term
loco-regional and systemic recurrence and, as secondary objectives, to provide
results of postoperative morbidity and the correlation between complete clinical
and pathological response. METHODS: This is a retrospective observational study
including a consecutive series of patients with T2-T3 superficial rectal cancer,
N0, M0 who refused radical surgery (2008-2016). The treatment consisted of
preoperative chemotherapy (5-fluorouracil or capecitabine) combined with
radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks.
Preoperative, surgical, pathological and long-term oncologic results were
analyzed. RESULTS: Twenty-four patients were included in the study. Two of them
required rescue radical surgery for unfavorable pathological results. A local
recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%),
with a median follow-up of 45 months. A complete clinical tumor response was
achieved in 12 patients (50%), and complete pathological tumor response in 9
patients (37.5%). Postoperative complications were observed in 5 patients
(20.8%), and they were mild except one. There was no postoperative mortality.
CONCLUSIONS: In this stage of rectal cancer, our results seem to support this
strategy, mainly when a complete pathological response is achieved. The complete
clinical tumor response does not coincide with the pathological tumor response.
Randomized prospective studies should be performed to standardize this treatment.
PMID- 28411890
TI - Time to rethink transanal endoscopic microsurgery for rectal cancer after
neoadjuvant chemoradiation for highly selected patients.
PMID- 28411887
TI - From Christian de Duve to Yoshinori Ohsumi: More to autophagy than just dining at
home.
AB - Christian de Duve first coined the expression "autophagy" during his seminal work
on the discovery of lysosomes, which led to him being awarded the Nobel Prize in
Physiology or Medicine in 1974. The term was adopted to distinguish degradation
of intracellular components from the uptake and degradation of extracellular
substances that he called "heterophagy". Studies until the 1990s were largely
observational/morphological-based until in 1993 Yoshinori Oshumi described a
genetic screen in yeast undergoing nitrogen deprivation that led to the isolation
of autophagy-defective mutants now better known as ATG (AuTophaGy-related) genes.
The screen identified mutants that fell into 15 complementation groups implying
that at least 15 genes were involved in the regulation of autophagy in yeast
undergoing nutrient deprivation, but today, 41 yeast ATG genes have been
described and many (though not all) have orthologues in humans. Attempts to
identify the genetic basis of autophagy led to an explosion in its research and
it's not surprising that in 2016 Yoshinori Oshumi was awarded the Nobel Prize in
Physiology or Medicine. Our aim here is not to exhaustively review the ever
expanding autophagy literature (>60 papers per week), but to celebrate Yoshinori
Oshumi's Nobel Prize by highlighting just a few aspects that are not normally
extensively covered. In an accompanying mini-review we address the role of
autophagy in early-diverging eukaryote parasites that like yeast, lack lysosomes
and so use a digestive vacuole to degrade autophagosome cargo and also discuss
how parasitized host cells react to infection by subverting regulation of
autophagy.
PMID- 28411891
TI - Recombinant expression of Thermobifida fusca E7 LPMO in Pichia pastoris and
Escherichia coli and their functional characterization.
AB - The discovery of lytic polysaccharides monooxygenases copper dependent (LPMOs)
revolutionized the classical concept that the cleavage of cellulose is a
hydrolytic process in recent years. These enzymes carry out oxidative cleavage of
cellulose (and other polysaccharides), acting synergistically with cellulases and
other hydrolases. In fact, LPMOs have the potential for increasing the efficiency
of the lignocellulosic biomass conversion in biofuels and high value chemicals.
Among a small number of microbial LPMOs that have been characterized, some LPMOs
were expressed and characterized biochemically from the bacteria Thermobifida
fusca, using the host Escherichia coli. In this work, the E7 LPMO protein of T.
fusca was expressed both in E. coli (native DNA sequence) and Pichia pastoris
(codon-optimized DNA sequence), for further analysis of oxidative cleavage, with
PASC (phosphoric acid swollen cellulose) and Avicel PH-101 substrates, using mass
spectrometry analysis. Mass spectra results of Avicel PH-101 and PASC cleavages
by purified E7 LPMO expressed in E. coli and in P. pastoris allowed the
visualization of compounds corresponding to oxidized and non-oxidized
oligosaccharides. Further optimization of reactions will be performed, since it
was found only one degree of polymerization (DP 7). This work demonstrated that
it is possible to produce the E7 LPMO from T. fusca in the host P. pastoris, and
the recombinant protein was shown to be active on cellulose. The approach used in
the present work could be an alternative to produce this bacterial LPMO for
cellulose cleavage.
PMID- 28411892
TI - Advanced penile cancer with iliac lymph node involvement treated with radiation
and concurrent gemcitabine.
AB - Penile cancer is a rare entity with only 2000 new cases a year in the United
States. Even though early stage penile cancer has an excellent prognosis,
patients with positive pelvic lymph nodes have an overall 5-year survival rate
under 10%. There is no consensus for the management of pelvic node-positive
patients, although most guidelines are in favour of pelvic lymph node dissection
for patients with two or more positive nodes, followed by adjuvant chemotherapy.
We describe here the case of a patient with numerous metastatic lymph nodes at
diagnosis, treated with chemoradiation (66Gy with concurrent gemcitabine) after
failure of first-line chemotherapy and still alive and disease-free 7 years after
diagnosis.
PMID- 28411893
TI - Genomic Approaches to Hypertension.
AB - Genomic insights and analyses of Mendelian hypertension (HTN) syndromes and
Genome-Wide Association study (GWAS) on essential hypertension have contributed
to the depth of understanding of the genetics origins of hypertension. Mendelian
syndromes are important for the field, since such knowledge leads to specific
insights about disease pathogenesis and the potential for precision medicine. The
clinical impact of findings of on essential hypertension is continuously
evolving, and the insights accrued will refine efforts to combat the societal
impact of hypertension. Comprehensive identification of all genomic variants of
hypertension, along with their individual associated mechanisms, is paving the
way forward in the era of personalized medicine. The overriding challenge for
care providers is to reduce health inequities through improved compliance and,
perhaps, new paradigms for implementation science that incorporate genomic
medicine.
PMID- 28411894
TI - The Effects of Dietary Factors on Blood Pressure.
AB - Evidence supports that multiple dietary factors affect blood pressure (BP).
Dietary changes that effectively lower BP are weight loss, reduced sodium intake,
increased potassium intake, moderation of alcohol intake, and Dietary Approaches
to Stop Hypertension-style and vegetarian dietary patterns. In view of the
increasing levels of BP in children and adults and the continuing epidemic of BP
related cardiovascular and renal diseases, efforts to reduce BP in both
nonhypertensive and hypertensive individuals are warranted. The challenge to
health care providers, researchers, government officials, and the general public
is developing and implementing clinical and public health strategies that lead to
sustained dietary changes.
PMID- 28411895
TI - The Environment and Blood Pressure.
AB - A host of environmental factors can significantly increase arterial blood
pressure (BP) including cold temperature, high altitude, loud noises, and ambient
air pollutants. Although brief exposures acutely elevate BP, over the long term,
chronic exposures may be capable of promoting the development of sustained
hypertension. Given their omnipresent nature, environmental factors may play a
role in worsening BP control and heightening overall cardiovascular risk at the
global public health level.
PMID- 28411897
TI - Management of Essential Hypertension.
AB - The treatment of essential hypertension is one of the most critical interventions
to decrease cardiovascular morbidity and mortality. The prevalence of
hypertension in the US varies across race/ethnicity with African Americans having
the highest prevalence and overall less control among racial/ethnic minorities
compared with non-Hispanic whites. Therapeutic lifestyle modifications are the
bedrock of essential hypertension control, but most patients with hypertension
will require pharmacotherapy, usually with multiple medications often in
combination. Overall, the principal drug classes recommended as initial
pharmacotherapy are thiazide-type diuretics, calcium channel blockers, and
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
PMID- 28411896
TI - Psychosocial Factors and Hypertension: A Review of the Literature.
AB - Black people have the highest prevalence of hypertension in the United States.
Evidence suggests that psychosocial factors increase the risks for hypertension
and help to account for racial differences in this condition. This article
reviews research on psychosocial factors and hypertension, and contextualizes the
findings within a health disparities framework. A wide range of psychosocial
factors contribute to hypertension but understanding remains limited about how
these factors relate to each other and accumulate to contribute to hypertension
disparities. Future research on psychosocial factors and hypertension needs to
enhance the effectiveness of interventions to reduce hypertension risk in ethnic
minority communities.
PMID- 28411898
TI - Balancing Overscreening and Underdiagnosis in Secondary Hypertension: The Case of
Fibromuscular Dysplasia.
AB - Knowledge about fibromuscular dysplasia (FMD) has broadened over the last several
decades. It is no longer considered a rare and benign entity limited to renal
arteries and causing just hypertension. It affects other parts of the arterial
tree nearly as frequently as the renal arteries. Complications of undiagnosed and
untreated extrarenal FMD can be debilitating and life threatening. However, this
disease, specifically extrarenal FMD, is not well known to many physicians and
patients. Combined with the nonspecific symptoms and signs of the disease, this
leads to delayed diagnosis and missed opportunity to prevent serious vascular
complications.
PMID- 28411899
TI - Device-Directed Therapy for Resistant Hypertension.
AB - Hypertension remains a significant risk factor for an array of diseases despite
advancements in pharmacotherapy. Patients with resistant hypertension who do not
respond to conventional medical treatments and lifestyle modifications are
especially at risk for poor health outcomes. With the increasing awareness of
resistant hypertension, ever-evolving research efforts continue to focus on
innovative interventions, including renal denervation, median nerve stimulation,
and baroreceptor activation therapy. This article reviews the current evidence
and summarizes previous clinical trials for each of these interventions.
PMID- 28411900
TI - Contemporary Approaches to Patients with Heart Failure.
AB - Incident heart failure and the burden of hospitalization may be demonstrating a
decline. However, as the population ages, the prevalence of heart failure
continues to increase. Mortality among heart failure patients is increasingly due
to non-cardiovascular causes. Current evidence-based therapy for heart failure
has improved heart failure related mortality. Current efforts should be directed
toward optimizing evidence based medical and device therapy, reducing morbidity,
and increasing quality of life with heart failure. Future clinical trials should
focus on therapies for heart failure with preserved ejection fraction,
regenerative therapy for heart failure, and optimizing durable mechanical support
for end-stage heart failure.
PMID- 28411901
TI - The Role of Implantable Hemodynamic Monitors to Manage Heart Failure.
AB - Heart failure is associated with high rates of hospitalization and
rehospitalization, resulting in substantial clinical and economic burden. Current
approaches to monitoring patients with heart failure have done little to reduce
these high rates of heart failure hospitalization. Implantable hemodynamic
monitors have been developed to remotely provide direct measurement of
intracardiac and pulmonary artery pressures in ambulatory patients with heart
failure. These devices have the potential to direct day-to-day management of
patients with heart failure to reduce hospitalization rates. The use of a
pulmonary artery pressure measurement system has been shown to reduce the risk of
heart failure hospitalization in patients with systolic and diastolic heart
failure.
PMID- 28411902
TI - Contemporary Drug-Eluting Stent Platforms: Design, Safety, and Clinical Efficacy.
AB - First-generation drug-eluting stents significantly improved treatment of coronary
disease, decreasing rates of revascularization. This was offset by high rates of
late adverse events, driven primarily by stent thrombosis. Research and design
improvements of individual DES platform components led to next-generation devices
with superior clinical safety and efficacy profiles compared with bare-metal
stents and first-generation drug-eluting stents. These design improvements and
features are explored, and their resulting clinical safety and efficacy reviewed,
focusing on platforms approved by the Food and Drug Administration currently
widely used in the United States.
PMID- 28411903
TI - Left Atrial Appendage Closure Device in Atrial Fibrillation.
AB - The relationship of stroke and atrial fibrillation seems to become more complex
as we gain more knowledge of the issue. Recent studies have questioned the
temporal relationship between the two, which also questions causation. Left
atrial appendage closure is an attractive, but unproven technology when compared
with the 50-year experience with warfarin. In a patient who is on warfarin and
having no issues with bleeding, medication intolerance, or lack of efficacy, it
is difficult to justify stopping the drug and placing a closure device as sole
therapy to prevent a stroke.
PMID- 28411905
TI - FPIES: The dark side of food allergy.
PMID- 28411906
TI - Serum levels of adiponectin and leptin in asthmatic patients and its relation
with asthma severity, lung function and BMI.
AB - INTRODUCTION: Asthma is one of the diseases which has a high prevalence in
developed and developing countries. The relationship between asthma and obesity
has always been focused by researchers. In this field, adipokines, especially
adiponectin and leptin have highly attended by the scientist. The aim of this
study was to determine the serum level of adiponectin, leptin and the
leptin/adiponectin ratio in asthmatic patients and its relationship with disease
severity, lung function and BMI (body mass index). METHODS: In this cross
sectional study, 90 asthmatic women admitted to the tertiary referral hospital in
Kurdistan province - Iran, were examined. First, BMI was measured and then
pulmonary function tests were performed in all asthmatics patient. Forced
expiratory volume in 1s (FEV1), forced vital capacity (FVC), and FEV1/FVC, were
measured. At the end, blood samples were collected and serum level of adiponectin
and leptin were measured by ELISA method. RESULT: Serum leptin and
leptin/adiponectin levels correlated positively with asthma severity and BMI
(p=0.0001), but there was no correlation between adiponectin level with asthma
severity and BMI (p>0.05), also serum leptin and leptin/adiponectin levels
inversely correlated with FEV1 and FVC in patient (p=0.0001). CONCLUSION: Asthma
is linked with obesity, and there is an association between asthma severity and
BMI with serum leptin and leptin/adiponectin levels, but our results do not
support a significant role of adiponectin in obesity or asthma.
PMID- 28411908
TI - Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal
Mass.
AB - The management of patients with hereditary kidney cancers presents unique
challenges to clinicians. In addition to an earlier age of onset compared with
patients with sporadic kidney cancer, those with hereditary kidney cancer
syndromes often present with bilateral and/or multifocal renal tumors and are at
risk for multiple de novo lesions. This population of patients may also present
with extrarenal manifestations, which adds an additional layer of complexity.
Physicians who manage these patients should be familiar with the underlying
clinical characteristics of each hereditary kidney cancer syndrome and the
suggested surgical approaches and recommendations of genetic testing for at-risk
individuals.
PMID- 28411907
TI - Epidemiology of the Small Renal Mass and the Treatment Disconnect Phenomenon.
AB - The incidence of kidney cancer has steadily increased over recent decades, with
most new cases now found when lesions are asymptomatic and small. This downward
stage migration relates to the increasing use of abdominal imaging. Three public
health epidemics-smoking, hypertension, and obesity-also play roles in the
increase. Treatment mirrors the rise in incidence, with increasing interest in
nephron-sparing therapies. Despite earlier detection and increasing treatment,
the mortality rate has not decreased. This treatment disconnect phenomenon
highlights the need to decrease unnecessary treatment of indolent tumors and
address modifiable risk factors to reduce incidence and mortality.
PMID- 28411909
TI - Current Trends in Renal Surgery and Observation for Small Renal Masses.
AB - There has been a rising incidence of small renal masses and concomitant downward
stage migration. This has led to an evolution in the management of kidney cancer
from radical nephrectomy to nephron-sparing treatment options including
observation. The adoption of partial nephrectomy continues to increase but is
still incomplete leading to significant disparities in the delivery of care
throughout the country. Surgical excision remains the treatment of choice for
small kidney cancers; however, ablative therapies and active surveillance are
emerging as reasonable options for select patients. With continued refinements in
treatment options and improvements in ability to risk stratify SRMs, the current
treatment trends will likely continue to evolve.
PMID- 28411910
TI - Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.
AB - Anatomic tumor complexity can be objectively measured and reported using
nephrometry. Various scoring systems have been developed in an attempt to
correlate tumor complexity with intraoperative and postoperative outcomes.
Nephrometry may also predict tumor biology in a noninvasive, reproducible manner.
Other scoring systems can help predict surgical complexity and the likelihood of
complications, independent of tumor characteristics. The accumulated data in this
new field provide provocative evidence that objectifying anatomic complexity can
consolidate reporting mechanisms and improve metrics of comparisons. Further
prospective validation is needed to understand the full descriptive and
predictive ability of the various nephrometry scores.
PMID- 28411911
TI - Risk Assessment in Small Renal Masses: A Review Article.
AB - The incidence of localized renal cell carcinoma (RCC) has been steadily
increasing, in large part because of the increased use of imaging. Optimizing the
management of localized RCC has become one of the leading priorities and foremost
challenges within the urologic-oncologic community. Adequate risk stratification
of patients following the diagnosis of localized RCC has become meaningful in
deciding whether to treat, how to treat, and how intensively to treat. This
article characterizes the existing risk assessment models that can be useful as
treatment decision aids for patients with localized RCC.
PMID- 28411912
TI - Current Role of Renal Biopsy in Urologic Practice.
AB - Most small renal masses (SRMs) are indolent. In fact, only approximately 80% of
SRMs are malignant. Furthermore, SRMs are commonly detected in elderly and
comorbid patients. Therefore, opportunities for better care intensity calibration
exist. Renal mass biopsy (RMB), when appropriately used, is a valuable clinical
tool to help with critical clinical decision-making in patients with SRM. This
article summarizes the role of modern RMB in helping gauge care for patients with
SRM.
PMID- 28411913
TI - Active Surveillance for the Small Renal Mass: Growth Kinetics and Oncologic
Outcomes.
AB - Active surveillance for small renal masses (SRMs) is an accepted management
strategy for patients with prohibitive surgical risk. Emerging prospectively
collected data support the concept that a period of initial active surveillance
in an adherent patient population with well-defined criteria for delayed
intervention is safe. This article summarizes the literature describing growth
kinetics of SRMs managed initially with observation and oncologic outcomes for
patients managed with active surveillance. Existing clinical tools to determine
and contextualize competing risks to mortality are explored. Finally, current
prospective clinical trials with defined eligibility criteria, surveillance
schema, and triggers for delayed intervention are highlighted.
PMID- 28411914
TI - Ablative Therapy for Small Renal Masses.
AB - The management of small renal masses has become an important public health topic.
The increased use of cross-sectional imaging and ultrasound has led to a downward
stage migration for the detection of small renal masses. Cancer-specific
survival, however, has not reflected this trend accordingly. Although partial
nephrectomy has been the mainstay of treatment of small renal masses less than 4
cm, there is growing interest in ablative therapies, such as cryoablation and
radiofrequency ablation, due to decreased morbidity. Oncologic outcomes are
limited by methodology and length of follow-up, but short-term recurrence rates
are low.
PMID- 28411915
TI - Surgical Techniques in the Management of Small Renal Masses.
AB - This article provides a review and outline of the various surgical techniques for
small renal masses. It covers surgical approaches and compares outcomes of open
versus minimally invasive surgery. The article discusses renal nephrometry
scoring and renal ischemia at time of resection. Techniques for controlling the
renal hilum and controlling blood flow to the kidney are described. Extirpative
techniques for small renal masses are reviewed along with a comparison of
outcomes. With careful adherence to key oncologic and surgical principles,
negative margins, no complications, and no or minimal decline in renal functional
outcomes can be achieved.
PMID- 28411916
TI - Renal Ischemia and Functional Outcomes Following Partial Nephrectomy.
AB - Renal function after renal cancer surgery is a critical component of
survivorship. Quantity and quality of preserved parenchyma are the most important
determinants of functional recovery; type and duration of ischemia play secondary
roles. Several studies evaluated surgical techniques to minimize ischemia;
however, long-term outcomes and potential benefits over clamped partial
nephrectomy (PN) have not been consistently demonstrated. Analysis of acute
kidney injury (AKI) after PN suggest that most kidneys recover strongly even if
AKI is experienced after surgery. Ongoing study is required to evaluate long-term
implications of AKI after PN and further assess impact of ischemia on functional
outcomes.
PMID- 28411917
TI - Comparative Effectiveness of Surgical Treatments for Small Renal Masses.
AB - In the management of small renal masses (SRMs), treatment options include partial
nephrectomy (PN), radical nephrectomy (RN), ablation, renal biopsy, and active
surveillance. Large series retrospective and meta-analyses demonstrate PN may
confer greater preservation of renal function, overall survival, and equivalent
cancer control when compared with RN. As newer therapies emerge, we should
critically evaluate the risks and benefits associated with the surgical
management of SRMs among patients with competing comorbidities, complex tumors,
and high-risk disease. Among younger patients with SRMs amenable to resection,
optimization of postoperative patient health should be prioritized.
PMID- 28411918
TI - Lymph Node Dissection for Small Renal Masses.
AB - Because the majority of small renal masses (SRMs; <4 cm) demonstrate low
metastatic potential and can be effectively treated with radical or partial
nephrectomy, the role of lymph node dissection (LND) at the time of surgery is
unclear. A randomized trial demonstrated no survival benefit of LND in clinically
localized renal cell carcinoma. Thus, LND is not recommended routinely for SRMs.
For patients with high-risk features or radiographic evidence of lymphadenopathy,
however, LND may improve local staging and potentially provide a survival
benefit. If performed, a LND template should be based on the known lymphatic
drainage of the kidneys.
PMID- 28411919
TI - Complications of Renal Surgery.
AB - The incidence of the small renal mass continues to increase owing to the aging
population and the ubiquity imaging. Most of these tumors are stage I tumors.
Management strategies include surveillance, ablation, and extirpation. There is a
wide body of literature favoring nephron-sparing approaches. Although nephron
sparing surgery may yield decreased long-term morbidity, it is not without its
drawbacks, including a higher rate of complications. Urologists must be attuned
to the complications of surgery and develop strategies to minimize risk. This
article reviews expected complications of surgery on renal masses and risk
stratification schema.
PMID- 28411920
TI - Neoadjuvant Targeted Molecular Therapy Before Renal Surgery.
AB - Neoadjuvant targeted molecular therapy may benefit select patients with
metastatic renal cell carcinoma. The primary use of this therapy in patients with
metastatic disease is to reduce tumor burden, prevent distant metastasis, and
increase overall survival. Neoadjuvant therapy may reduce tumor size and tumor
complexity, facilitate partial nephrectomy rather than radical nephrectomy,
downstage tumor thrombus facilitating thrombectomy, and make unresectable tumors
resectable when applied to selected patients. These potential benefits of
neoadjuvant therapy require further clinical trials to better define the renal
function and oncological and survival outcomes in patients receiving each active
agent.
PMID- 28411921
TI - Salvage Surgery After Renal Mass Ablation.
AB - Thermal ablative techniques represent treatment options for patients with small
renal masses who are not candidates for surgery. The oncologic efficacy of
ablation has not been compared in a randomized fashion with nephron-sparing
surgery, and the urologist must be knowledgeable regarding the workup and
treatment of patients with suspected residual or recurrent tumor following these
therapies. Surveillance of patients with tumor recurrence after ablation may be
indicated in select circumstances. When patients are deemed appropriate for
salvage therapy, most undergo a repeat course of the same ablative modality.
Salvage surgery is possible but often complicated by the prior ablative
techniques.
PMID- 28411922
TI - Postoperative Surveillance for Renal Cell Carcinoma.
AB - Postoperative surveillance is an integral part of renal cell carcinoma (RCC)
care. However, evidence supporting the practice is lacking. RCC guidelines offer
disparate recommendations leading to variation in care. Recently, the
effectiveness of guidelines has been questioned and a debate has ignited over
whether current protocols merit optimization. Guidelines show limitations in RCC
risk assessment, protocol stratification, and definition of duration of follow
up. Alternative strategies have addressed some of these limitations, but further
analysis is warranted. Until challenges with assessing a survival benefit are
negotiated, efforts should be made to optimize and standardize guidelines and
learn of more tangible benefits to surveillance.
PMID- 28411923
TI - Erratum.
PMID- 28411924
TI - Small Renal Mass.
PMID- 28411925
TI - The Small Renal Mass and Its Management in Urologic Practice.
PMID- 28411926
TI - Advances in the Prevention and Treatment of High Altitude Illness.
AB - High altitude illness encompasses a spectrum of clinical entities to include:
acute mountain sickness, high altitude cerebral edema, and high altitude
pulmonary edema. These illnesses occur as a result of a hypobaric hypoxic
environment. Although a mild case of acute mountain sickness may be self-limited,
high altitude cerebral edema and high altitude pulmonary edema represent critical
emergencies that require timely intervention. This article reviews recent
advances in the prevention and treatment of high altitude illness, including new
pharmacologic strategies for prophylaxis and revised treatment guidelines.
PMID- 28411927
TI - Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia.
AB - Accidental hypothermia is an unintentional drop in core temperature to 35 degrees
C or below. Core temperature is best measured by esophageal probe. If core
temperature cannot be measured, the degree should be estimated using clinical
signs. Treatment is to protect from further heat loss, minimize afterdrop, and
prevent cardiovascular collapse during rescue and resuscitation. The patient
should be handled gently, kept horizontal, insulated, and actively rewarmed.
Active rewarming is also beneficial in mild hypothermia but passive rewarming
usually suffices. Cardiopulmonary resuscitation should be performed if there are
no contraindications to resuscitation. CPR may be delayed or intermittent.
PMID- 28411928
TI - Frostbite.
AB - Deep frostbite is a thermal injury associated with significant morbidity.
Historically, this has been associated with military personnel; however,
increasingly it is becoming an injury that afflicts the civilian population. The
use of intravenous iloprost or intra-arterial thrombolytics has led to promising
tissue salvage. This article provides an up-to-date understanding of frostbite
pathophysiology, classification, prevention, and management. It also highlights
the role of telemedicine in optimizing patient outcomes. To further the
understanding of optimal frostbite management, larger, likely multicenter, high
quality trials are required. An international frostbite register would facilitate
data gathering.
PMID- 28411929
TI - Updates in Decompression Illness.
AB - Decompression sickness and arterial gas embolism, collectively known as
decompression illness (DCI), are rare but serious afflictions that can result
from compressed gas diving exposures. Risk is primarily determined by the
pressure-time profile but is influenced by several factors. DCI can present
idiosyncratically but with a wide range of neurologic symptoms. Examination is
critical for assessment in the absence of diagnostic indicators. Many conditions
must be considered in the differential diagnosis. High-fraction oxygen breathing
provides first aid but definitive treatment of DCI is hyperbaric oxygen.
PMID- 28411930
TI - Marine Envenomation.
AB - Venomous aquatic animals are hazardous to swimmers, surfers, divers, and
fishermen. Exposures include mild stings, bites, abrasions, and lacerations.
Severe envenomations can be life threatening. This article reviews common marine
envenomations, exploring causative species, clinical presentation, and current
treatment recommendations. Recommendations are included for cnidaria, sponges,
bristle worms, crown-of-thorns starfish, sea urchins, venomous fish, stingrays,
cone snails, stonefish, blue-ringed octopus, and sea snakes. Immediate and long
term treatment options and management of common sequelae are reviewed. Antivenom
administration, treatment of anaphylaxis, and surgical indications are discussed.
PMID- 28411931
TI - North American Snake Envenomation.
AB - Native US snakes that produce clinically significant envenomation can be divided
into 2 groups, crotalids and elapids. The crotalids include rattlesnakes,
cottonmouths, and copperheads. Crotalid envenomation can result in significant
local tissue damage as well as thrombocytopenia and coagulopathy. Rarely are
bites fatal. Native US elapids are all coral snakes that possess neurotoxic venom
that can cause weakness, respiratory paralysis, and rarely death. Treatment of
both types of envenomation revolves around general supportive care and antivenom
administration when indicated. Previously advocated treatments, such as
tourniquets, venom extraction, and bite site excision are not recommended.
PMID- 28411932
TI - Arthropod Envenomation in North America.
AB - Arthropods (phylum Arthopoda) account for a higher percentage of morbidity and
mortality to humans than do mammalian bites, snake bites, or marine envenomation.
They are ubiquitous in domestic dwellings, caves, and campsites and in wilderness
settings such as deserts, forests, and lakes. Although arthropods are most
intrusive during warmer months, many are active throughout the winter,
particularly indoors. Arthropods are also nocturnal and often bite unsuspecting
victims while they are sleeping. Encounters with humans are generally defensive,
accidental, or reactive. An individual stung by an insect or bitten by an
arachnid may experience pain and local swelling, an anaphylactic reaction, or
life-threatening toxicity. This review discusses the clinical presentation and
latest treatment recommendations for bites and stings from spiders, scorpions,
bees, ants, ticks and centipedes of North America.
PMID- 28411933
TI - Wilderness Emergency Medical Services Systems.
AB - Wilderness emergency medical services (WEMS) are designed to provide high quality
health care in wilderness environments. A WEMS program should have oversight by a
qualified physician responsible for protocol development, education, and quality
improvement. The director is also ideally fully trained as a member of that
wilderness rescue program, supporting the team with real-time patient care. WEMS
providers function with scopes of practice approved by the local medical director
and regulatory authority. With a focus on providing quality patient care, it is
time for the evolution of WEMS as an integrated element of a local emergency
response system.
PMID- 28411934
TI - Tactical Combat Casualty Care and Wilderness Medicine: Advancing Trauma Care in
Austere Environments.
AB - Tactical Combat Casualty Care (TCCC) is a set of evidence-based, best-practice
prehospital trauma care guidelines customized for use on the battlefield.
Military units that have trained all of their unit members in TCCC have now
documented the lowest incidence of preventable deaths in the history of modern
warfare and TCCC is now the standard for battlefield trauma care in the US
Military. TCCC and wilderness medicine share the goal of optimizing care for
patients with trauma in austere environments that impose significant challenges
in both equipment and evacuation capability. This article reviews the current
battlefield trauma care recommendations in TCCC and discusses their applicability
to the wilderness setting.
PMID- 28411935
TI - Point-of-Care Ultrasound in Austere Environments: A Complete Review of Its
Utilization, Pitfalls, and Technique for Common Applications in Austere Settings.
AB - With the advent of portable ultrasound machines, point-of-care ultrasound (POCUS)
has proven to be adaptable to a myriad of environments, including remote and
austere settings, where other imaging modalities cannot be carried. Austere
environments continue to pose special challenges to ultrasound equipment, but
advances in equipment design and environment-specific care allow for its
successful use. This article describes the technique and illustrates pathology of
common POCUS applications in austere environments. A brief description of common
POCUS-guided procedures used in austere environments is also provided.
PMID- 28411936
TI - Is There a Doctor Onboard? Medical Emergencies at 40,000 Feet.
AB - It is estimated 2.75 billion people travel aboard commercial airlines every year
and 44,000 in-flight medical emergencies occur worldwide each year. Wilderness
medicine requires a commonsense and improvisational approach to medical issues. A
sudden call for assistance in the austere and unfamiliar surroundings of an
airliner cabin may present the responding medical professional with a "wilderness
medicine" experience. From resource management to equipment, this article sheds
light on the unique conditions, challenges, and constraints of the flight
environment.
PMID- 28411937
TI - Preparing for International Travel and Global Medical Care.
AB - Thorough pretravel preparation and medical consultation can mitigate avoidable
health and safety risks. A comprehensive pretravel medical consultation should
include an individualized risk assessment, immunization review, and discussion of
arthropod protective measures, malaria prophylaxis, traveler's diarrhea, and
injury prevention. Travel with children and jet lag reduction require additional
planning and prevention strategies; travel and evacuation insurance may prove
essential when traveling to less resourced countries. Consideration should also
be given to other high-risk travel scenarios, including the provision of health
care overseas, adventure and extreme sports, water environments and diving, high
altitude, and terrorism/unstable political situations.
PMID- 28411938
TI - Medicolegal Issues in Expedition and Wilderness Medicine.
AB - There is increased participation in wilderness expeditions to remote and austere
environments, which increases the likelihood of an accident and/or medical
emergency and the professional liability risks for trip organizers. Trip
organizers, outfitters, tour guides, and health care providers must understand
the medicolegal liabilities involved in and the legal protection and immunity
available when rendering care in austere and challenging settings to mitigate
risks and prepare for the level of medical care that may be required. There is a
great deal of variability in the legal protections provided by Good Samaritan
laws and interpretations may differ among jurisdictions.
PMID- 28411939
TI - Erratum.
PMID- 28411940
TI - Wilderness and Environmental Medicine.
PMID- 28411941
TI - Wilderness and Environmental Medicine.
PMID- 28411942
TI - Transplacental nutrient transfer in the human in vivo determined by 4 vessel
sampling.
AB - BACKGROUND: The intrauterine environment and especially the fetal nutritional
conditions affect lifelong health. There are few human in vivo studies on fetal
nutrition. The importance to test experimentally based concepts of fetal
nutrition in a human in vivo setting is becoming increasingly apparent. A way of
testing nutrient transfer in human is 4-vessel sampling, which implies blood
sampling from artery and vein on both sides of the placenta. Here we give a brief
review of the studies using the 4-vessel sampling method. METHOD: We performed
systematic searches in Ovid MEDLINE and EMBASE (Ovid) from 1946 to May 2016. The
following search terms were used to identify eligible articles: [placenta] AND
[glucose/blood glucose] OR [amino acids] OR [lipids] OR [cholesterol] OR
[nutrient] AND [blood sample] OR [biological transport] OR
[transport/transfer/exchange] OR [maternal-fetal exchange] AND [humans]. RESULTS:
The search retrieved 623 studies. After abstract scanning 25 full text articles
were evaluated and seven articles describing 4-vessel sampling were identified.
The studies had from 14 to 77 participants and reported placental transfer of
different nutrients (glucose, lactate, amino acids and arachidonic acid).
CONCLUSION: Few studies have used 4 vessel sampling to study placental nutrient
transfer in human pregnancies. Overall these studies indicate that the transfer
of nutrients between the mother and the fetus is highly "dynamic," i.e. most
nutrients may pass either way on both the maternal and fetal sides of the
placenta. Furthermore, the concept that the placenta is a metabolically highly
active organ affecting transfer of glucose, amino acids and lipids, fits the
human in vivo data. The 4-vessel method can provide essential information on the
transfer between the mother, placenta and fetus of virtually any compound.
PMID- 28411943
TI - Immunomodulatory properties of human placental mesenchymal stem/stromal cells.
AB - Mesenchymal stem/stromal cells (MSCs) are isolated from various fetal and adult
tissues such as bone marrow, adipose tissue, cord blood and placenta. Placental
MSCs (pMSCs), the main focus of this review, are relatively new MSC types that
are not as intensively studied compared with bone marrow-derived MSCs (BMMSCs).
MSCs modulate the immune functions of important immune cells involved in
alloantigen recognition and elimination, including antigen presenting cells
(APCs), T cells, B cells and natural killer (NK) cells. Clinical trials, both
completed and underway, employ MSCs to treat various human immunological
diseases, such as multiple sclerosis (MS) and type 1 diabetes. However, the
mechanisms that mediate the immunosuppressive effects of pMSCs are still largely
unknown, and the safety of pMSC use in clinical settings needs further
confirmation. Here, we review the current knowledge of the immunosuppressive
properties of placental MSCs.
PMID- 28411944
TI - Differentiation of amniotic epithelial cells into various liver cell types and
potential therapeutic applications.
AB - The aim of Regenerative Medicine is to replace or regenerate human cells, tissues
or organs in order to restore normal function. Among all organs, the liver is
endowed with remarkable regenerative capacity. Nonetheless, there are conditions
in which this ability is impaired, and the use of isolated cells, including stem
cells, is being considered as a possible therapeutic tool for the management of
chronic hepatic disease. Placenta holds great promise for the field of
regenerative medicine. It has long been used for the treatment of skin lesions
and in ophthalmology, due to its ability to modulate inflammation and promote
healing. More recently, cells isolated from the amniotic membrane are being
considered as a possible resource for tissue regeneration, including in the
context liver disease. Two cell types can be easily isolated from human amnion:
epithelial cells (hAEC) and mesenchymal stromal cells (hAMSC). However only the
first cell population has been demonstrated to be a possible source of proficient
hepatic cells. This review will summarize current knowledge on the
differentiation of hAEC into liver cells and their potential therapeutic
application.
PMID- 28411945
TI - Shallow rocky nursery habitat for fish: Spatial variability of juvenile fishes
among this poorly protected essential habitat.
AB - Coastal nursery habitats are essential for the renewal of adult fish populations.
We quantified the availability of a coastal nursery habitat (shallow
heterogeneous rocky bottoms) and the spatial variability of its juvenile fish
populations along 250km of the Catalan coastline (France and Spain). Nurseries
were present in 27% of the coastline, but only 2% of them benefited from strict
protection status. For nine taxa characteristic of this habitat, total juvenile
densities varied significantly between nursery sites along the coastline, with
the highest densities being found on the northern sites. Recruitment level (i.e.
a proxy of nursery value) was not explained by protection level, but it was
moderately and positively correlated with an anthropization index. Patterns of
spatial variations were taxa-specific. Exceptional observations of four juveniles
of the protected grouper Epinephelus marginatus were recorded. Our data on
habitat availability and recruitment levels provides important informations which
help to focus MPA management efforts.
PMID- 28411946
TI - Introduction.
PMID- 28411947
TI - Central line-associated bloodstream infections in the NICU: Successes and
controversies in the quest for zero.
AB - Central line-associated bloodstream infections (CLABSI) are among the most common
healthcare-acquired infections in the neonatal intensive care unit (NICU)
population and are associated with an increased risk of morbidity and mortality,
as well as increased healthcare costs, and duration of hospitalization. Over the
past decade, numerous local, statewide, and national quality improvement
initiatives have resulted in a significant reduction in CLABSI rates. The
majority of successful initiatives have utilized similar strategies to implement
and sustain their efforts, including education of NICU staff in the principles of
quality improvement, creation and implementation of central line insertion and
maintenance bundles and methods for assessing compliance, formation of dedicated
central line insertion and maintenance teams, and utilization of reliable and
effective methods for collecting, analyzing, and displaying data. Despite this
progress, continued work toward discovery of better practices, such as the safest
and most effective agent for cutaneous antisepsis or identification of optimal
outcome and process measures, is required if further progress is to be made.
Additionally, sustained progress in reducing the burden of neonatal infections
may require a shift in focus away from CLABSI and toward the reporting,
investigation, and prevention of all NICU-onset bacteremia.
PMID- 28411948
TI - Reporting 'Denominator' data is essential for benchmarking and quality standards
in ovarian cancer.
AB - OBJECTIVE: Combined surgery and platinum-based chemotherapy is the
internationally agreed standard therapy for advanced ovarian cancer (AOC).
However international cancer registry datasets demonstrate a significant
proportion of patients do not receive both or either therapies. Our objective was
to evaluate the effect of total patient cohort data ('Denominator') on median
overall survival (OS) and determine how frequently this was reported in
literature. METHODS: We retrospectively reviewed OS outcomes for 593 patients
diagnosed with AOC for 77 months at a regional cancer centre. Patients were
stratified into five progressively overlapping categories based on treatment
received - Primary debulking surgery (PDS), PDS or Interval debulking (IDS), all
surgery and those considered for IDS, patients receiving any treatment and total
patient cohort. A systematic search of literature was performed. RESULTS: Median
OS progressively decreased from 54.5 months in patients receiving PDS, 38.7
months in the PDS+IDS group, 35.4 months in the PDS/IDS+patients considered for
IDS, 33.3 months in patients receiving any treatment and 30.2 months in the total
patient cohort. OS in the surgically treated group was statistically
significantly different from the OS in the total patient cohort
(Denominator)(p=0.000353). Denominator descriptors were identified in 11% of
studies. CONCLUSIONS: Denominator data is critical to understanding selection and
OS in AOC. Published outcomes of selected cohorts should routinely incorporate
outcomes for all women managed within the reporting Centre. This is essential for
benchmarking and quality assurance in gynaecological cancer and should be an
integral part of any publication on outcomes from AOC.
PMID- 28411949
TI - Reliability of Echocardiographic Indicators of Pulmonary Vascular Disease in
Preterm Infants at Risk for Bronchopulmonary Dysplasia.
AB - OBJECTIVES: To determine the assessment and inter-rater reliability of
echocardiographic evaluations of pulmonary vascular disease (PVD) in preterm
infants at risk for bronchopulmonary dysplasia. STUDY DESIGN: We prospectively
studied echocardiograms from preterm infants (birthweights 500-1250 g) at 7 days
of age and 36 weeks postmenstrual age (PMA). Echocardiograms were assessed by
both a cardiologist on clinical service and a single research cardiologist.
Interpretations were reviewed for inclusion of determinants of PVD and assessed
for inter-rater reliability using the Prevalence Adjusted Bias Adjusted Kappa
Score (PABAK). RESULTS: One hundred eighty and 188 matching research and clinical
echocardiogram reports were available for the 7-day and 36-week PMA studies. At
least one of the specific qualitative measures of PVD was missing from 54% of the
clinical reports. PVD was diagnosed at 7 days in 31% and 20% of research and
clinical interpretations, respectively (PABAK score of 0.54). At 36 weeks, PH was
diagnosed in 15.6% and 17.8% of research and clinical interpretations,
respectively (PABAK score of 0.80). CONCLUSIONS: Although all qualitative
variables of PVD are not consistently provided in echocardiogram reports, the
inter-rater reliability of cardiologists evaluating measures of PVD revealed
strong agreement, especially at 36 weeks PMA. We speculate that establishment of
a protocol for echocardiographic evaluation may improve the identification of PVD
in preterm infants.
PMID- 28411950
TI - Priorities to Advance Monitoring of Ecosystem Services Using Earth Observation.
AB - Managing ecosystem services in the context of global sustainability policies
requires reliable monitoring mechanisms. While satellite Earth observation offers
great promise to support this need, significant challenges remain in quantifying
connections between ecosystem functions, ecosystem services, and human well-being
benefits. Here, we provide a framework showing how Earth observation together
with socioeconomic information and model-based analysis can support assessments
of ecosystem service supply, demand, and benefit, and illustrate this for three
services. We argue that the full potential of Earth observation is not yet
realized in ecosystem service studies. To provide guidance for priority setting
and to spur research in this area, we propose five priorities to advance the
capabilities of Earth observation-based monitoring of ecosystem services.
PMID- 28411951
TI - Reply to: "Considerations about: "Prevalence of hypertension and hypertension
phenotypes by age and gender among schoolchildren in Greece: The Healthy Growth
Study"".
PMID- 28411952
TI - Improved design of constrained model predictive tracking control for batch
processes against unknown uncertainties.
AB - In this paper, an improved constrained tracking control design is proposed for
batch processes under uncertainties. A new process model that facilitates process
state and tracking error augmentation with further additional tuning is first
proposed. Then a subsequent controller design is formulated using robust stable
constrained MPC optimization. Unlike conventional robust model predictive control
(MPC), the proposed method enables the controller design to bear more degrees of
tuning so that improved tracking control can be acquired, which is very important
since uncertainties exist inevitably in practice and cause model/plant
mismatches. An injection molding process is introduced to illustrate the
effectiveness of the proposed MPC approach in comparison with conventional robust
MPC.
PMID- 28411953
TI - Adaptive fuzzy control of a class of nonaffine nonlinear system with input
saturation based on passivity theorem.
AB - In this paper, based on the passivity theorem, an adaptive fuzzy controller is
designed for a class of unknown nonaffine nonlinear systems with arbitrary
relative degree and saturation input nonlinearity to track the desired
trajectory. The system equations are in normal form and its unforced dynamic may
be unstable. As relative degree one is a structural obstacle in system
passivation approach, in this paper, backstepping method is used to circumvent
this obstacle and passivate the system step by step. Because of the existence of
uncertainty and disturbance in the system, exact passivation and reference
tracking cannot be tackled, so the approximate passivation or passivation with
respect to a set is obtained to hold the tracking error in a neighborhood around
zero. Furthermore, in order to overcome the non-smoothness of the saturation
input nonlinearity, a parametric smooth nonlinear function with arbitrary
approximation error is used to approximate the input saturation. Finally, the
simulation results for the theoretical and practical examples are given to
validate the proposed controller.
PMID- 28411954
TI - n-3 Polyunsaturated Fatty Acids for the Management of Patients With Chronic
Kidney Disease.
PMID- 28411955
TI - Message From the Chairperson.
PMID- 28411956
TI - Medical Nutrition Therapy for Pediatric Kidney Stone Prevention, Part 3:
Cystinuria.
PMID- 28411957
TI - Elevated temperature adhesion of bioinspired polymeric micropatterns to glass.
AB - Micropatterned polymer surfaces that operate at various temperatures are required
for emerging technical applications such as handling of objects or space debris.
As the mechanical properties of polymers can vary significantly with temperature,
adhesion performance can exhibit large variability. In the present paper, we
experimentally study temperature effects on the adhesion of micropatterned
adhesives (pillar length 20um, aspect ratios 0.4 and 2) made from three different
polymers, i.e., polydimethylsiloxane (PDMS), perfluoropolyether dimethacrylate
(PFPEdma), and polyurethane (PU-ht). PU specimens showed the highest pull-off
stresses of about 57kPa at 60 degrees C, i.e., more than twice the value of
unpatterned control samples. The work of separation similarly showed a maximum at
that temperature, which was identified as the glass transition temperature, Tg.
PDMS and PFPEdma specimens were tested above their Tg. As a result, the adhesion
properties decreased monotonically (about 50% for both materials) for temperature
elevation from 20 to 120 degrees C. Overall, the results obtained in our study
indicate that the operating temperature related to the glass transition
temperature should be considered as a significant parameter for assessing the
adhesion performance of micropatterned adhesives and in the technical design of
adhesion devices.
PMID- 28411958
TI - Effects of step length and step frequency on lower-limb muscle function in human
gait.
AB - The aim of this study was to quantify the effects of step length and step
frequency on lower-limb muscle function in walking. Three-dimensional gait data
were used in conjunction with musculoskeletal modeling techniques to evaluate
muscle function over a range of walking speeds using prescribed combinations of
step length and step frequency. The body was modeled as a 10-segment, 21-degree
of-freedom skeleton actuated by 54 muscle-tendon units. Lower-limb muscle forces
were calculated using inverse dynamics and static optimization. We found that
five muscles - GMAX, GMED, VAS, GAS, and SOL - dominated vertical support and
forward progression independent of changes made to either step length or step
frequency, and that, overall, changes in step length had a greater influence on
lower-limb joint motion, net joint moments and muscle function than step
frequency. Peak forces developed by the uniarticular hip and knee extensors, as
well as the normalized fiber lengths at which these muscles developed their peak
forces, correlated more closely with changes in step length than step frequency.
Increasing step length resulted in larger contributions from the hip and knee
extensors and smaller contributions from gravitational forces (limb posture) to
vertical support. These results provide insight into why older people with weak
hip and knee extensors walk more slowly by reducing step length rather than step
frequency and also help to identify the key muscle groups that ought to be
targeted in exercise programs designed to improve gait biomechanics in older
adults.
PMID- 28411959
TI - Implementation and outcomes of an antimicrobial stewardship program:
Effectiveness of education.
AB - BACKGROUND: Unnecessary use of antibiotics is a common occurrence in hospitals.
Implementation of antibiotic stewardship programs (ASPs) has been shown to reduce
both unnecessary antibiotic use and drug-resistant bacteria. Education is a
fundamental component of an ASP. However, the effectiveness of proper uses of
antibiotics education has not been clearly analyzed. METHODS: In a 520-bed
university hospital located in northeastern Taiwan, a significantly increasing
prescription of carbapenems, specifically imipenem and meropenem, was observed.
An educational program highlighting the judicious use of carbapenems was started,
beginning in October 2013. A multidisciplinary ASP was implemented starting in
January 2014. The consumption of antibiotics, measured by defined daily dose per
1000 occupied bed-days, was compared among the pre-educational, posteducational,
and post-ASP periods. RESULTS: Compared with the pre-educational period, there
was a significant reduction in antibiotics consumption of 13% total inpatient
antibiotics (p = 0.008), 29.8% carbapenems (p = 0.001), 34.9% imipenem and
meropenem (p < 0.001), and 27% glycopeptides (p = 0.015), in the posteducational
and post-ASP periods. The major reduction emerged during the posteducational
period and was sustained after the ASP. The percentage of inpatients prescribed
with antibiotics was significantly decreased (16.2%; p < 0.001). The rate of
carbapenem-resistant Acinetobacter baumannii decreased from 70.8% to 29.6% within
7 months. CONCLUSION: A focused educational program is effective in controlling
the prescription of specific antibiotic classes in the early phase of a
multidisciplinary ASP.
PMID- 28411960
TI - Age and gender influences on the needs, concerns and strategies of CABG
caregivers.
AB - BACKGROUND: Caring for coronary artery bypass (CABG) surgery patients can be
challenging. No studies have explored caregiver burden by age and gender.
OBJECTIVE: To describe age and gender-specific concerns, needs and strategies
during the first 3 months. METHODS: Themes for burden concerns, needs and
strategies were derived from interviews of 32 CABG caregivers using constant
comparative analysis. RESULTS: Age-specific themes related to motivating exercise
(<70), applying support hose, and self-reliance (>70). Gender-specific themes
related to incision worries and transportation (all females); regulating blood
sugars, vital sign anxiety, hurrying back, reinforcing healthy behaviors, and
being there (females <70); meal planning, coordinating appointments, and anger
over self-care reminders (females >70); caregiver relief, inconsistent
information, and doing it all (all males); upsetting scars (males <70), and lost
sleep (male >70). CONCLUSIONS: Future research should validate concerns in
diverse samples so interventions can be targeted to support male and female
caregivers by age groups.
PMID- 28411961
TI - Nutrition in the first 1000 days and respiratory health: A descriptive review of
the last five years' literature.
AB - The aim of this paper is to discuss the current evidence regarding short and long
term health respiratory effects of nutrients and dietary patterns during the
first 1000 days from conception. Population of interest included children from
birth to two years and their mothers (during pregnancy and lactation). Studies
were searched on MEDLINE(r) and Cochrane database, inserting individually and
using the Boolean ANDs and ORs, 'nutrients', 'micronutrients', 'LC-PUFA',
'Mediterranean Diet', 'human milk', 'complementary food', 'pregnancy',
'respiratory disease', 'pulmonary disease', 'asthma', 'epigenetics', 'first 1000
days', 'maternal diet' and 'respiratory health'. All sources were retrieved
between 01-09-2015 and 07-12-2016. While unhealthy maternal dietary patterns
(high fat intake) during pregnancy can result in alteration of foetal lung
development, with increased risk of respiratory disorders, Mediterranean diet has
been associated with a lower risk of allergic sensitisation and allergic
rhinitis. Breastfeeding has beneficial effects on respiratory infections while
evidences about its protective effect on allergic disorders are unclear. During
complementary feeding there is no evidence to avoid or encourage exposition to
'highly allergenic' foods to have modification of tolerance development. In
children from birth to two years of age, Mediterranean diet has been associated
with a lower risk of atopy, wheezing and asthma. Micronutrients, antioxidant and
LCPUFA supplementation is not recommended and a whole food approach should be
preferred, except for Vitamin D.
PMID- 28411962
TI - Epidemiology and pathophysiology of malignancy in common variable
immunodeficiency?
AB - Common variable immunodeficiency (CVID) is a diagnostic category of primary
immunodeficiency (PID) which may present with heterogeneous disorders including
recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other
types of malignancies. Generally, the incidence of malignancy in CVID patients is
around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non
Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours
of stomach, breast, bladder and cervix. The exact pathological mechanisms for
cancer development in CVID are not fully determined; however, several mechanisms
including impaired genetic stability, genetic predisposition, immune
dysregulation, impaired clearance of oncogenic viruses and bacterial infections,
and iatrogenic causes have been proposed to contribute to the high susceptibility
of these patients to malignancies.
PMID- 28411963
TI - Using a knowledge-based planning solution to select patients for proton therapy.
AB - BACKGROUND AND PURPOSE: Patient selection for proton therapy by comparing
proton/photon treatment plans is time-consuming and prone to bias. RapidPlanTM, a
knowledge-based-planning solution, uses plan-libraries to model and predict organ
at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan,
utilizing an algorithm based only on photon beam characteristics, could generate
proton DVH-predictions and whether these could correctly identify patients for
proton therapy. MATERIAL AND METHODS: ModelPROT and ModelPHOT comprised 30 head
and-neck cancer proton and photon plans, respectively. Proton and photon
knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH
prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR
doses. KBPs and manual plans were compared using salivary gland and swallowing
muscle mean doses. For illustration, patients were selected for protons if
predicted ModelPHOT mean dose minus predicted ModelPROT mean dose
(DeltaPrediction) for combined OARs was >=6Gy, and benchmarked using achieved KBP
doses. RESULTS: Achieved and predicted ModelPROT/ModelPHOT mean dose R2 was
0.95/0.98. Generally, achieved mean dose for ModelPHOT/ModelPROT KBPs was
respectively lower/higher than predicted. Comparing ModelPROT/ModelPHOT KBPs with
manual plans, salivary and swallowing mean doses increased/decreased by <2Gy, on
average. DeltaPrediction>=6Gy correctly selected 4 of 5 patients for protons.
CONCLUSIONS: Knowledge-based DVH-predictions can provide efficient, patient
specific selection for protons. A proton-specific RapidPlan-solution could
improve results.
PMID- 28411964
TI - Understanding what matters: An exploratory study to investigate the views of the
general public for priority setting criteria in health care.
AB - Health care policy makers internationally are increasingly expressing commitment
to consultation with, and incorporation of, the views of the general public into
the formulation of health policy and the process of setting health care
priorities. In practice, however, there are relatively few opportunities for the
general public to be involved in health care decision-making. In making resource
allocation decisions, funders, tasked with managing scarce health care resources,
are often faced with difficult decisions in balancing efficiency with equity
considerations. A mixed methods (qualitative and quantitative) approach
incorporating focus group discussions and a ranking exercise was utilised to
develop a comprehensive list of potential criteria for setting priorities in
health care formulated from the perspective of members of the general public in
Australia. A strong level of congruence was found in terms of the rankings of the
key criteria with the size of the health gain, clinical effectiveness, and the
ability to provide quality of life improvements identified consistently as the
three most important criteria for prioritising the funding of an intervention.
Findings from this study will be incorporated into a novel DCE framework to
explore how decision makers and members of the general public prioritize and
trade off different types of health gain and to quantify the weights attached to
specific efficiency and equity criteria in the priority setting process.
PMID- 28411965
TI - Dynamic Cerebral Autoregulation Assessment Using Extracranial Internal Carotid
Artery Doppler Ultrasonography.
AB - Transcranial Doppler ultrasonography of the middle cerebral artery (MCA) is
frequently used to assess dynamic cerebral autoregulation (dCA); however, this is
difficult in patients with poor temporal bone windows. In the study described
here, we investigated the agreement and sensitivity of dCA indices determined
from the extracranial internal carotid artery (ICA) and those determined from the
MCA. Measurements for 32 stroke patients and 59 controls were analyzed.
Measurement of the mean flow correlation index (Mx) and transfer function
analysis based on spontaneous blood pressure fluctuation were simultaneously
performed for the extracranial ICA and MCA. The mean values of Mx and phase shift
did not significantly differ between the ICA and MCA (mean difference: Mx = 0.01;
phase shift of very low frequency [VLF] = 0.7 degrees , low frequency [LF] = 3.3
degrees and high frequency = 4.5 degrees ), but the gains in VLF and LF in the
ICA were significantly lower than those in the MCA (mean difference: gain of VLF
= -0.13, gain of LF = -0.10). The intra-class correlation coefficient between the
dCA indices of the ICA and MCA was favorable in Mx (0.76) and the phase shift of
VLF (0.72). The area under the receiver operating characteristic curve for stroke
diagnosis did not differ among the dCA indices. We conclude that dCA assessed
from the ICA is as effective as that from the MCA, but the results are not
interchangeable.
PMID- 28411966
TI - Ultrasound Screening for Adverse Local Tissue Reaction after Hip Arthroplasty.
AB - Early detection of adverse local tissue reaction (ALTR) to prosthetic hip wear
debris is vital to improve the success of revision surgery. Magnetic resonance
imaging with metal artefact reduction sequencing (MARS MRI) is considered the
modality of choice to provide cross-sectional imaging of the soft tissues. The
areas adjacent to the prosthesis are, however, not readily imaged using these
protocols. Ultrasound has also been recommended as an imaging modality in the
follow-up of hip replacement surgery. We decided to characterise the typical
ultrasound findings in a group of patients undergoing routine biennial review of
arthroplastic hips with particular reference to the hip capsule, femoral neck and
iliopsoas bursa and tendon adjacent to the implant. Fifty-two patients with a
mean (+/-SD) age of 60.4 (+/-12) y were prospectively recruited. Twelve patients
had bilateral hip prostheses, giving 64 hips for analysis. Mean (+/-SD) age of
the prosthesis in situ was 8.2 (+/-3.3) y. Data were grouped on the basis of the
shape of the iliofemoral ligament. The median (range) maximal anteroposterior
synovial thickness was 5 (2-8) mm in the normal concave iliofemoral ligament
group and 7 (4-56) mm in the abnormal straight/convex iliofemoral ligament group
(p = 0.001). The anteroposterior iliopsoas tendon measurement was 5 (3-8) mm in
the normal group and 5 (4-8) mm in the abnormal group (p = 0.065). ALTR
development in asymptomatic well-functioning prostheses may be recognised earlier
using ultrasound rather than MARS MRI by carefully assessing the shape of the
iliofemoral ligament. Ultrasound findings of an abnormal straight or convex
ligament may be suggestive of early ALTR and warrant streaming of patients to a
more frequent surveillance program.
PMID- 28411968
TI - Waterlining, Shebanging, and Monkey Water: An Unrecognized Route of Heroin Abuse.
PMID- 28411967
TI - Utility of relative ADC ratio in patient selection for endovascular
revascularization of large vessel occlusion.
AB - PURPOSE: The relative apparent diffusion coefficient (ADC) ratio on magnetic
resonance imaging (MRI) can be used to evaluate the degree of ischemia. Here, we
assessed the predictability of ischemic reversibility and the risk of hemorrhagic
transformation using the relative ADC ratio. METHODS: This single-center
retrospective study analyzed 56 patients with acute occlusion of the internal
carotid artery (ICA) or the middle cerebral artery (M1) with endovascular
revascularization. Diffusion-weighted imaging (DWI) lesions were classified as
reversible lesions, final infarct lesions, and hemorrhagic or non-hemorrhagic
regions. The relative ADC ratio was calculated in each DWI lesion and was defined
as the ratio of ADC pixel values within affected territory to ADC pixel values in
contralateral normal brain regions. RESULTS: The average relative ADC ratio was
0.890+/-0.045 in reversible DWI lesion and 0.640+/-0.041 in final infarct DWI
lesion (P<0.001). In 4 cases with hemorrhagic transformation, hemorrhagic
transformation regions were 0.557+/-0.049 and non-hemorrhagic transformation
regions were 0.762+/-0.042 (P<0.001). In addition, percentage DWI improvement was
inversely correlated with DWI lesion volume at the time of hospitalization (r=
0.840) and onset-to-reperfusion time (r=-0.765), but no correlation was noted
with patient age (r=-0.043) or the first NIHSS score (r=-0.277). CONCLUSIONS: The
relative ADC ratio may be useful for predicting DWI reversibility and post
reperfusion hemorrhagic transformation, even in patients with an unknown time of
onset.
PMID- 28411969
TI - Valproate-Induced Hyperammonemic Encephalopathy in General Hospital Patients With
One or More Psychiatric Disorders.
AB - BACKGROUND: Divalproex sodium/valproic acid (VPA) is an antiepileptic drug
approved for use in epilepsy and bipolar disorder. Valproate-induced
hyperammonemia occurs in up to 50% of VPA-treated patients, some of whom may
become encephalopathic. Valproate-induced hyperammonemic encephalopathy (VHE) is
thought to be rare, and for a variety of reasons, the diagnosis requires a high
index of suspicion. OBJECTIVE: The study's goals are to determine how common VHE
is, and the quality of treatment provided when diagnosed. METHODS: Retrospective,
cross-sectional survey of general hospital patients. The hospital's laboratory
and pharmacy databases were combined to identify a cohort of all VPA-treated
patients who developed hyperammonemia during a 5-year period. Hospital records of
the subset of patients with a psychiatric disorder were selected and reviewed for
data collection. RESULTS: Twenty of 793 (2.52%) VPA-treated patients had signs
and symptoms consistent with VHE. The majority were White males on multiple
psychotropic agents. Valproate was appropriately discontinued in 8 (40%)
patients. Lactulose was the only ammonia-lowering drug used, and it was
administered to 6 patients and only one among them had VPA discontinued.
CONCLUSION: Study results indicate that VHE may be more common in psychiatric
patients than previously assumed but underrecognized and inadequately treated.
The diagnosis of VHE requires a high index of suspicion. Outcome is favorable
once it is recognized and treated appropriately.
PMID- 28411970
TI - Long-term outcomes of the New Jersey nurse faculty preparation program scholars.
AB - BACKGROUND: Rising concerns over the capacity of nursing education to prepare
enough nurses to meet population demand have received national attention. The
Robert Wood Johnson Foundation implemented the New Jersey Nursing Initiative
Faculty Preparation Program to address nursing workforce issues in New Jersey.
PURPOSE: This paper describes program and scholar outcomes and provides
recommendations for nurse faculty development. METHODS: This descriptive study
uses data from scholar surveys and interviews with grantees. DISCUSSION: Findings
suggest that a faculty preparation program that targets doctoral students and
includes financial support, socialization to the faculty role, and formal
education courses produces graduates who maintain a career in nursing education
for up to three years after program completion. However, most master's-level
students who also received formal preparation in nursing education were employed
in clinical practice. CONCLUSIONS: Program developers must carefully consider the
design of programs that integrate faculty preparation and advanced clinical
training for master's-level students.
PMID- 28411971
TI - MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney
donors.
AB - INTRODUCTION: The evaluation of the measured Glomerular Filtration Rate (mGFR) or
estimated Glomerular Filtration Rate (eGFR) is key in the proper assessment of
the renal function of potential kidney donors. We aim to study the correlation
between glomerular filtration rate estimation equations and the measured methods
for determining renal function. MATERIAL AND METHODS: We analysed the
relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene
triamine-pentaacetate) and those estimated by the four-variable Modification of
Diet in Renal Disease (MDRD4) and Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equations in a series of living donors at our
institution. RESULTS: We included 64 donors (70.6% females; mean age 48.3+/-11
years). Baseline creatinine was 0.8+/-0.1 mg/dl and it was 1.1+/-0.2 mg/dl one
year after donation. The equations underestimated GFR when measured by Tc99m-DTPA
(MDRD4-9.4 +/- 25ml/min, P<.05, and CKD-EPI-4.4 +/- 21ml/min). The correlation
between estimation equations and the measured method was superior for CKD-EPI
(r=.41; P<.004) than for MDRD4 (r=.27; P<.05). eGFR decreased to 59.6+/-11
(MDRD4) and 66.2+/-14ml/min (CKD-EPI) one year after donation. This means a mean
eGFR reduction of 28.2+/-16.7 ml/min (MDRD4) and 27.31+/-14.4 ml/min (CKD-EPI) at
one year. CONCLUSIONS: In our experience, CKD-EPI is the equation that better
correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening
purposes.
PMID- 28411972
TI - Influence of cognitive style on information processing and selection of yogurt
labels: Insights from an eye-tracking study.
AB - Cognitive styles are characteristic and stable ways in which people acquire,
organize and use information for solving problems and making decisions. Field
dependence/independence is one of the most studied cognitive styles. Field
independent subjects are characterized by having less difficulty in separating
information from its contextual surroundings and being less likely to be
influenced by external cues than field dependent individuals. The present work
aimed at studying the influence of field dependence/independence cognitive style
on consumers' visual processing and choice of yogurt labels. One hundred and
thirty three consumers completed a choice conjoint task. They were asked to
select their preferred yogurt label from each of 16 pairs of labels. While they
completed the task their eye movements were recorded using an eye-tracker. Then,
consumers were asked to complete the Group Embedded Figure Test to determine
their cognitive style. Consumers were divided into two groups with different
cognitive styles: 58% of the sample was characterized as field dependent and 42%
as field independent. When making their choices, field dependent consumers tended
to engage in less thoughtful information processing than field independent
consumers and they made fewer fixations on traditional nutritional information.
Besides, cognitive style significantly affected the relative importance of fat
and sugar content on consumer choices and modulated the influence of the traffic
light system. Field dependent consumers gave less importance to the nutritional
composition of the yogurts than field independent consumers for selecting their
preferred label. Results from this work suggest that studying the psychological
underpinnings of consumers' decision making process when selecting food products
has a great potential to contribute to a better understanding of how eating
patterns and consumer preferences are shaped.
PMID- 28411973
TI - Antioxidants: Characterization, natural sources, extraction and analysis.
AB - Recently many review papers regarding antioxidants from different sources and
different extraction and quantification procedures have been published. However
none of them has all the information regarding antioxidants (chemistry, sources,
extraction and quantification). This article tries to take a different
perspective on antioxidants for the new researcher involved in this field.
Antioxidants from fruit, vegetables and beverages play an important role in human
health, for example preventing cancer and cardiovascular diseases, and lowering
the incidence of different diseases. In this paper the main classes of
antioxidants are presented: vitamins, carotenoids and polyphenols. Recently, many
analytical methodologies involving diverse instrumental techniques have been
developed for the extraction, separation, identification and quantification of
these compounds. Antioxidants have been quantified by different researchers using
one or more of these methods: in vivo, in vitro, electrochemical,
chemiluminescent, electron spin resonance, chromatography, capillary
electrophoresis, nuclear magnetic resonance, near infrared spectroscopy and mass
spectrometry methods.
PMID- 28411974
TI - Improvement of radio frequency (RF) heating uniformity on low moisture foods with
Polyetherimide (PEI) blocks.
AB - Radio frequency (RF) heating is rapid, volumetric, and can penetrate most food
packaging material. Thus, it is suited for in-packaged food pasteurization
applications. However, the non-uniform heating problem needs to be resolved. In
this study, a method of adding Polyetherimide (PEI) cylindrical blocks on top of
and at the bottom of peanut butter samples in a cylindrical jar (d=10cm, h=5cm)
was evaluated to improve RF heating uniformity. A computer simulation model built
with COMSOL Multiphysics(r) was used for heating pattern prediction, and a new
temperature uniformity index was proposed to suitably evaluate pasteurization
process heating uniformity. Results showed that a pair of PEI blocks with a
diameter of 8cm among all five diameters (2, 4, 6, 8, and 10cm) added to the cold
spots of a given peanut butter sample could make the sample reach the best
heating uniformity. Furthermore, the best height of PEI blocks with a diameter of
8cm that allows the sample to be heated most uniformly was found to be 1.3cm
after sweeping from 0.1 to 2.3cm with a step of 0.1cm. Simulation results also
showed that the combination of PEI surrounding and the addition of 8cm diameter
PEI blocks could further control the temperature distribution range in peanut
butter within 7.1 degrees C when the peanut butter was heated from 23 to 70
degrees C. The newly developed temperature uniformity index provided a more
reasonable evaluation on heating uniformity of pasteurization process than the
traditional uniformity index.
PMID- 28411975
TI - Application of microsatellite markers as potential tools for traceability of
Girgentana goat breed dairy products.
AB - In livestock, breed assignment may play a key role in the certification of
products linked to specific breeds. Traceability of farm animals and
authentication of their products can contribute to improve breed profitability
and sustainability of animal productions with significant impact on the rural
economy of particular geographic areas and on breed and biodiversity
conservation. With the goal of developing a breed genetic traceability system for
Girgentana dairy products, the aim of this study was to identify specific
microsatellite markers able to discriminate among the most important Sicilian
dairy goat breeds, in order to detect possible adulteration in Girgentana dairy
products. A total of 20 microsatellite markers were analyzed on 338 individual
samples from Girgentana, Maltese, and Derivata di Siria goat breeds. Specific
microsatellite markers useful for traceability of dairy products were identified.
Eight microsatellite markers showed alleles present at the same time in Maltese
and Derivata di Siria and absent in Girgentana and, therefore, they were tested
on DNA pools of the three breeds. Considering the electropherograms' results,
only FCB20, SRCRSP5, and TGLA122 markers were tested on DNA samples extracted
from cheeses of Girgentana goat breed. These three microsatellite markers could
be applied in a breed genetic traceability system of Girgentana dairy products in
order to detect adulteration due to Maltese and Derivata di Siria goat breeds.
PMID- 28411976
TI - How do Brazilian consumers perceive a non-traditional and innovative fruit juice?
An approach looking at the packaging.
AB - Consumer interest in nutritious and innovative foods encourages the development
of products based on raw materials with nutraceutical potential. The health
benefits provided by pomegranate have been recognized; therefore, the development
of pomegranate juice may match consumer expectations regarding this goal.
However, the concept has to first be accepted by the consumer. The aim of the
study was to utilize a rating based conjoint analysis to investigate how
Brazilian consumers perceive pomegranate juice by identifying the role of
packaging attributes relevant to the consumer's intention to purchase. Five
factors were considered in the study: technology used in the juice production
(high hydrostatic pressure - HHP - a technology that preserves nutritional and
sensory properties), antioxidants, price, preservatives, and colorant. Eight
hypothetical pomegranate juice packages were created following an incomplete
block design and evaluated by 150 fruit juice consumers. Three clusters were
identified. The average results revealed that antioxidants were the attribute of
greatest relative importance to cluster 1 (RI: 36%), followed by HHP (RI: 25%)
and colorants (14%). Consumers in cluster 2 considered price as the most
important attribute (RI: 41%), followed by antioxidants (RI: 21%) and HHP (RI:
18%). Cluster 3, as well as cluster 2, considered price the most important
attribute (RI: 28%), followed by antioxidants (RI: 26%) and HHP (RI: 22%). The
results showed that consumers valued information on the health benefits of
antioxidants as well as on the technology, suggesting that both types of
information may be relevant tools to increase the intention to purchase the
product. The application of HHP for pomegranate juice processing was positively
perceived by consumers, suggesting a potential commercial application in the
Brazilian industry.
PMID- 28411977
TI - Influence of anionic dietary fibers (xanthan gum and pectin) on oxidative
stability and lipid digestibility of wheat protein-stabilized fish oil-in-water
emulsion.
AB - The influence of two anionic dietary fibers (xanthan gum and pectin) on the
oxidative stability and lipid digestibility of fish oil emulsions stabilized by
wheat protein (gliadin) was investigated. Lipid oxidation was determined by
measuring lipid hydroperoxides and TBARS of the emulsions during storage, while
protein oxidation was measured using fluorescence spectroscopy. Lipid and protein
oxidation was faster at pH3.5 than at pH7, which may have been due to increased
iron solubility under acidic conditions. Xanthan gum inhibited lipid and protein
oxidation, which was attributed to its ability to bind iron ions. Conversely,
pectin promoted oxidation, which was attributed to the presence of endogenous
transition metals in the polysaccharide ingredient. In vitro digestion was
carried out to evaluate the digestibility of oil droplets in emulsions with or
without polysaccharides. Both xanthan gum and pectin significantly increased the
rate of lipid digestion, which was attributed to their ability to inhibit droplet
aggregation under gastrointestinal conditions. These results have important
implications for designing emulsion-based functional foods with improved
oxidative stability and lipid digestibility.
PMID- 28411978
TI - Safety evaluation of tangeretin and the effect of using emulsion-based delivery
system: Oral acute and 28-day sub-acute toxicity study using mice.
AB - Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging
group of bioactive compounds with wide arrays of disease prevention
functionalities. To understand the potential oral toxicity, tangeretin, being one
of the most abundant polymethoxyflavones from natural sources, was used as model
compound for the safety evaluation. Acute oral toxicity study was conducted using
both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of
tangeretin in oil suspension from single gavage administration. No evidence of
death was observed during 14-day post-administration period. Alterations of the
hepatic cell and clinical chemistry profile increased dose dependently and
exhibited distinct injury recovery pattern among different sexes. To determine
the potential safety concern related to emulsification, the sub-acute toxicity of
tangeretin in emulsion was evaluated and compared with un-processed oil
suspension when conducting the sub-acute toxicity study over 28days. In the sub
acute study, emulsion system did not induce a significant increase of toxicity
response. However, the daily low-dose application of tangeretin showed U-shaped
dose-response pattern in regard to hepatic alteration. The result from this study
can serve as a good safety reference for future application of polymethoxyflavone
as a functional ingredient in food.
PMID- 28411979
TI - Peroxidase (POD) and polyphenol oxidase (PPO) photo-inactivation in a coconut
water model solution using ultraviolet (UV).
AB - The interest in coconut water as a beverage is increasing due, not only to its
sensory properties, but also to its nutritional characteristics. Even so, several
challenges limit its processing, the inactivation of the polyphenol oxidase (PPO)
and peroxidase (POD) enzymes being the most important. Although the inactivation
of these enzymes has been extensively studied in coconut water, both by
conventional and emerging technologies, the technologies evaluated so far are
either not effective in the inactivation of these enzymes and/or result in
undesirable changes. This work evaluated the photo-inactivation of POD and PPO in
a coconut water model solution using ultraviolet radiation (UV). Both enzymes
showed continuous inactivation behaviour in relation to the processing time, this
being described by a two-portion inactivation kinetics. A possible mechanism for
the observed photo-inactivation was proposed, involving steps of molecular
unfolding and aggregation. The POD activity after 15min of processing was ~5% of
its original value, and reduced to ~1% after 30min of UV processing. After 15min
of processing, PPO activity was ~8% of its original value, falling to ~2% after
30min of UV processing. The results obtained highlight the potential use of the
ultraviolet radiation to inactivate both enzymes in coconut water.
PMID- 28411980
TI - Stability of flocculated particles in concentrated and high hydrophilic solid
layer-by-layer (LBL) emulsions formed using whey proteins and gum Arabic.
AB - The objective of the present study was to investigate flocculation in layer-by
layer (LBL) emulsion systems with high total solids content and deflocculation at
various pH conditions, and the effects of whey protein isolate (WPI)
concentration and total solids content on the stability of LBL emulsions. WPI
(1.96% (1WPI) or 10.71% (10WPI), w/w in water) was prepared in water and high
pressure homogenized with sunflower oil (10%, w/w, of total emulsion). Gum Arabic
(0.15%, w/w, in total emulsion) was added to assemble electrostatically on WPI at
oil particle interfaces at pH3.5 using aqueous citric acid (10% w/w) forming LBL
emulsion. The zeta-potential measurements showed charge reversal upon addition of
gum Arabic solution into single layer (SL) emulsion confirming the formation of
LBL interface. Trehalose:maltodextrin mixture (1:1, w/w, total emulsion, 28.57%
(28) or 57.14% (57), w/w, in water) was used in the continuous phase. The high
total solids content of the system results in depletion flocculation of the
particles leading to bridging flocculation without coalescence as deflocculation
into individual particles occurred with increasing pH from pH3.5 to pH6.5 in
10WPI systems. Deflocculation was evident in 10WPI-28 and 10WPI-57 as found from
a decreased zeta-average diameter and visually under microscope. Coalescence was
observed in 1WPI systems. Viscosity of the systems was significantly (P<0.05)
increased with higher total solids content. Accelerated destabilization test
showed that systems at higher WPI and total solids contents exhibited the highest
stability against creaming. Deflocculation in LBL systems can be controlled by pH
while high solids in the aqueous phase provide stability against creaming.
PMID- 28411981
TI - Sweetness potency and sweetness synergism of sweeteners in milk and coffee
systems.
AB - This study investigated the presence of sweetness synergism in milk and instant
coffee systems. It consists of three parts: 1) modeling concentration-sweetness
intensity curves of sweeteners (stevia, sucralose, xylose, tagatose and
erythritol); 2) measuring the sweetness potencies of sweeteners compared to
sucrose at wide concentration range; and 3) investigating the presence of
sweetness synergisms in binary sweetener mixtures. The panelists evaluated
sweetness and other sensory characteristics of sweeteners using descriptive
analysis. Based on the modeled curve derived from step 1, the concentration of
each sweetener with sweetness intensity equal to 2.5% or 2.8% sucrose was
calculated for milk and coffee systems, respectively. For the sweetness synergism
study, one type of intense sweetener was mixed with one type of bulk sweetener,
each eliciting 2.5% or 2.8% equi-sweetness to sucrose, and compared with 5%
sucrose added to a milk system or 5.6% sucrose added to a coffee system. The
sweetness potencies of bulk sweeteners generally increased whereas the sweetness
potencies of intense sweeteners decreased as the concentration increased. The
binary sweetener mixtures mostly showed additivity in milk and suppression in
coffee system rather than synergism when the concentration dependent nature of
sweetness potency for each sweetener was taken into account.
PMID- 28411982
TI - Interactions of caseins with phenolic acids found in chocolate.
AB - To investigate the interactions between caseins and phenolic acids, such as the
ones present in chocolate, casein was incubated with protocatechuic acid or p
coumaric acid at 55 degrees C. In addition, casein was isolated from chocolate
and the phenolic compounds within these caseins were quantified. Electrophoresis
results revealed that casein-phenolic interactions were induced by incubation;
minor aggregation of casein subunits was observed after incubation of casein with
protocatechuic acid. Minor aggregation of casein isolated from milk chocolate was
also observed. In vitro hydrolysis of casein control, casein-protocatechuic acid,
casein-p-coumaric acid, caseins isolated from milk chocolate and white chocolate
using trypsin showed degree of hydrolysis of 19.3, 18.6, 17.7, 10.4 and 17.8%
respectively. The presence of protocatechuic acid and p-coumaric acid in the
model system and the presence of phenolic compounds in milk chocolate, in
addition to the structural changes occurring during processing, affected the
peptide profiles of casein hydrolysates.
PMID- 28411983
TI - Biologically active peptides: Processes for their generation, purification and
identification and applications as natural additives in the food and
pharmaceutical industries.
AB - Recent technological advances have created great interest in the use of
biologically active peptides. Bioactive peptides can be defined as specific
portions of proteins with 2 to 20 amino acids that have desirable biological
activities, including antioxidant, anti-hypertensive, antithrombotic, anti
adipogenic, antimicrobial and anti-inflammatory effects. Specific
characteristics, including low toxicity and high specificity, make these
molecules of particular interest to the food and pharmaceutical industries. This
review focuses on the production of bioactive peptides, with special emphasis on
fermentation and enzymatic hydrolysis. The combination of different technologies
and the use of auxiliary processes are also addressed. A survey of isolation,
purification and peptide characterization methods was conducted to identify the
major techniques used to determine the structures of bioactive peptides. Finally,
the antioxidant, antimicrobial, anti-hypertensive, anti-adipogenic activities and
probiotic-bacterial growth-promoting aspects of various peptides are discussed.
PMID- 28411984
TI - Capability of exopolysaccharide-producing Lactobacillus paraplantarum BGCG11 and
its non-producing isogenic strain NB1, to counteract the effect of
enteropathogens upon the epithelial cell line HT29-MTX.
AB - The putative protective role of the exopolysaccharide (EPS)-producing
Lactobacillus paraplantarum BGCG11, and its non-EPS-producing isogenic strain
NB1, was tested upon HT29-MTX monolayers challenged with seven opportunistic
pathogens. The probiotic strain Lactobacillus rhamnosus LMG18243 (GG) was used as
a reference bacterium. Tested lactobacilli were able to efficiently reduce the
attachment to HT29-MTX of most pathogens. Lb. paraplantarum NB1 and Lb. rhamnosus
GG were more efficient reducing the adhesion of Clostridium difficile or Yersinia
enterocolitica than Lb. paraplantarum BGCG11, while strain BGCG11 reduced, to a
greater extent, the adhesion of Escherichia coli and Listeria monocytogenes. The
detachment and cell lysis of HT29-MTX monolayers in the presence of pathogens
alone and co-incubated with lactobacilli or purified EPS was followed. L.
monocytogenes induced the strongest cell detachment among the seven tested
pathogens and this effect was prevented by addition of purified EPS-CG11. The
results suggest that this EPS could be an effective macromolecule in protection
of HT29-MTX cells from the pathogen-induced lysis. Regarding innate intestinal
barrier, the presence of C. difficile induced the highest IL-8 production in HT29
MTX cells and this capability was reinforced by the co-incubation with Lb.
paraplantarum NB1 and Lb. rhamnosus GG. However, the increase in IL-8 production
was not noticed when C. difficile was co-incubated with EPS-producing Lb.
paraplantarum BGCG11 strain or its purified EPS-CG11 polymer, thus indicating
that the polymer could hinder the contact of bacteria with the intestinal
epithelium. The measurement of mucus secreted by HT29-MTX and the expression of
muc1, muc2, muc3B and muc5AC genes in the presence of pathogens and lactobacilli
suggested that all lactobacilli strains are weak "co-adjuvants" helping some
pathogens to slightly increase the secretion of mucus by HT29-MTX, while purified
EPS-CG11 did not induce mucus secretion. Taking altogether, Lb. paraplantarum
BGCG11 could act towards the reinforcement of the innate mucosal barrier through
the synthesis of a physical-protective EPS layer which could make difficult the
contact of the pathogens with the epithelial cells.
PMID- 28411986
TI - Changes in dietary fiber fractions and gut microbial fermentation properties of
wheat bran after extrusion and bread making.
AB - The dietary fiber in wheat bran, principally non-starch polysaccharides (NSP), is
mostly water-unextractable and is poorly utilized by human gut microbiota. The
purpose of this study was to determine the change in water-extractability of NSP
in wheat bran upon extrusion and then to determine if extrusion impacts the
availability of NSP for fermentation by the fecal microbiota during in vitro
fecal fermentation. A secondary objective was to incorporate extruded bran into a
product formulation to determine if changes in WE-NSP and NSP fermentation were
maintained in a finished product. Bran was extruded using combinations of high or
low moisture (15% and 30% wb) and high or low screw speed (120 and 250rpm). All
extrusion conditions resulted in increases in WE-NSP and fecal microbiota short
chain fatty acid (SCFA) production upon fermentation compared with unextruded
bran. Low screw speed and low moisture resulted in the greatest increase in WE
NSP (3-fold) as well as the highest production of SCFA during fermentation (1.4
fold) compared with unextruded bran. Whole wheat breads containing extruded bran
did not show increases in either WE-NSP or SCFA production compared with the
control. In conclusion, extrusion of wheat bran increased WE-NSP, which enabled
greater fermentability by human fecal microbiota. However, once extruded bran was
used in a whole wheat bread formulation the changes in fermentation outcomes were
no longer evident.
PMID- 28411985
TI - Stability of probiotic Lactobacillus plantarum in dry microcapsules under
accelerated storage conditions.
AB - This study investigated the stability of freeze dried and fluid bed dried
alginate microcapsules coated with chitosan containing model probiotic bacteria,
Lactobacillus plantarum, during storage for up to 45days at different water
activities (0.11, 0.23, 0.40 and 0.70) and temperatures (4, 30 and 37 degrees C).
The loss in cell viability was around 0.8 log in the case of fluid bed drying and
around 1.3 in the case of freeze drying, with the former method resulting in
dried capsules of smaller size (~1mm vs 1.3mm), more irregular shape, and with a
rougher surface. In both cases, the water activity and water content were less
than 0.25 and 10% w/w, respectively, which favours high storage stability. The
storage stability studies demonstrated that as the water activity and temperature
decreased the survival of the dried encapsulated cells increased. Considerably
better survival was observed for fluid bed dried encapsulated cells compared to
freeze dried encapsulated cells and freeze dried free cells with 10% sucrose
(control), and in some cases, e.g. at 4 and 30 degrees C at water activities of
0.11, 0.23 and 0.40, there was more than 1 log difference after 45days, with
concentrations higher than 108CFU/g after 45days of storage. The results indicate
that fluid bed drying is an effective and efficient manufacturing method to
produce probiotic containing capsules with enhanced storage stability.
PMID- 28411987
TI - Structural and viscoelastic characterization of ternary mixtures of sunflower
oil, saturated monoglycerides and aqueous phases containing different bases.
AB - The structure at different length scales and the viscoelastic properties of
ternary mixtures composed of saturated monoglycerides, sunflower oil and aqueous
solutions of weak bases (KHCO3, NaHCO3, and NH4HCO3) or strong bases (NaOH and
KOH) were investigated. The characteristics of ternary mixtures were studied
systematically by using polarized light microscopy, differential scanning
calorimetry (DSC), synchrotron X-ray diffraction (XRD) and rheological analysis.
Results showed that the base type and concentration greatly affected the
structure of the mixtures. The use of strong bases allowed gelled systems to be
obtained only at low concentrations (<10mM). On the contrary, the presence of
weak bases induced gelling at all concentrations considered (from 1 to 1000mM).
The increase of base concentration led to a reduction of the mean droplet
diameter and melting temperature. At the same time, the viscoelastic
characteristics as a function of base concentration followed a more complex
behavior: G' and G" progressively decreased as the salt concentration increased
in a concentration range from 1 to 100mM, while the rheological parameters
increased when salt concentration increased from 100 to 1000mM. The structural
and viscoelastic behavior of systems prepared with different salts were commonly
independent of the cation present in the medium. Results highlight that it is
possible to tailor the structure of these gels by using specific bases.
PMID- 28411988
TI - Effect of drying, storage temperature and air exposure on astaxanthin stability
from Haematococcus pluvialis.
AB - Astaxanthin is a powerful antioxidant with various health benefits such as
prevention of age-related macular degeneration and improvement of the immune
system, liver and heart function. To improve the post-harvesting stability of
astaxanthin used in food, feed and nutraceutical industries, the biomass of the
high astaxanthin producing alga Haematococcus pluvialis was dried by spray- or
freeze-drying and under vacuum or air at -20 degrees C to 37 degrees C for
20weeks. Freeze-drying led to 41% higher astaxanthin recovery compared to
commonly-used spray-drying. Low storage temperature (-20 degrees C, 4 degrees C)
and vacuum-packing also showed higher astaxanthin stability with as little as
12.3+/-3.1% degradation during 20weeks of storage. Cost-benefit analysis showed
that freeze-drying followed by vacuum-packed storage at -20 degrees C can
generate AUD$600 higher profit compared to spray-drying from 100kgH. pluvialis
powder. Therefore, freeze-drying can be suggested as a mild and more profitable
method for ensuring longer shelf life of astaxanthin from H. pluvialis.
PMID- 28411990
TI - Qualitative and nutraceutical aspects of lemon fruits grown on the mountainsides
of the Mount Etna: A first step for a protected designation of origin or
protected geographical indication application of the brand name 'Limone
dell'Etna'.
AB - The cultivation of lemon (Citrus limon (L.) Burm f.) has occurred for centuries
at the mountainsides of the Mount Etna the largest active volcano in Europe
(Sicily, Italy). The peculiar geographical, soil and climatic conditions that
characterize this area have recently prompted citrus growers to launch the brand
name 'Limone dell'Etna' for the lemon fruits produced in that area. The present
research focused on evaluating the quality and nutraceutical properties of the
'Limone dell'Etna' fruit juice ('Primofiore', 'Bianchetto', and 'Verdello'
blooming) to enhance the value of a product that, due to its peculiar qualities,
could be awarded with one of the European certified labels protecting the lemon
geographical origin. Qualitative parameters, health-promoting components (such as
ascorbic acid, flavonoids, and hydroxycinnamic acids) and the in-vitro total
antioxidant capacity (ORAC, FCR) of fruit juice of two different varieties
('Femminello zagara bianca' and 'Monachello') were determined at fruit maturity.
The results showed that the Bianchetto and Verdello lemon fruit exhibited higher
levels of ascorbic acid than those recorded for the Primofiore production. The
amount of flavonoids in Verdello fruits of both cultivars was the highest, as was
reflected in the highest antioxidant activity. Thus, the 'Limone dell'Etna'
production, with particular reference to the Verdello fruit, must be considered
as a new, valuable and original source of natural antioxidants to be valorized
and even exploited in the processing industry.
PMID- 28411989
TI - Partridgeberry polyphenols protect primary cortical and hippocampal neurons
against beta-amyloid toxicity.
AB - beta-Amyloid (Abeta) deposition elicits a toxic effect on neurons and plays a
crucial role in the etiology and/or progression of Alzheimer's disease (AD).
Polyphenols found in fruits are endorsed for nutritional intervention in AD,
since they are known to have extensive therapeutic properties apropos of brain
health owing to their anti-oxidative effects against Abeta and neural reactive
oxygen species (ROS). The present study was aimed to investigate the
neuroprotective potential of polyphenols of partridgeberry (Vaccinium vitis-idaea
L.) and elucidate the mechanism by which they confer protection against Abeta
toxicity in rat primary neurons in vitro. The pre-treatment of rat primary
cortical and hippocampal neurons with partridgeberry polyphenols (10-200MUgmL-1)
significantly attenuated Abeta-induced cell death and membrane damage. The flavan
3-ol- and flavonol-rich fractions of the partridgeberry exhibited the strongest
ability to maintain cell viability (EC50 5.9MUgmL-1) and prevent lactose
dehydrogenase release (IC50 0.01MUgmL-1) (P<=0.05). Similar to the maintenance of
cellular viability, the flavan-3-ol- and flavonol-rich fractions also amplified
the greatest activity of SOD and catalase among all polyphenol preparations
exposed to neurons (P<=0.05). All four partridgeberry polyphenol preparations
reduced the intracellular Abeta levels by 7-15 folds, and initiated Abeta
clearance from neurons as compared to untreated cells (P<=0.05). Partridgeberry
derived polyphenol preparations; especially the flavonol-rich fraction (IC50
97.1MUgmL-1) significantly modulated the apoptotic targets and in vitro
acetylcholinesterase activity (P<=0.05), indicating potential pharmacotherapy
application in AD. Furthermore, the restoration of hyperactive caspases and Bcl2
family of apoptotic architects added to the neuroprotective candidacy of PPFs.
These findings suggest that partridgeberry polyphenols, especially flavan-3-ol-
and flavonol-rich fractions, could be of importance in prevention and/or
treatment of AD.
PMID- 28411991
TI - Effect of carrier oils on the physicochemical properties of orange oil beverage
emulsions.
AB - In this study, the effect of carrier oils on the physicochemical properties of
orange oil beverage emulsions was investigated. The beverage emulsions were
prepared by soybean soluble polysaccharides (SSPS) using a two-stage processing
of homogenization. Results showed that the presence of carrier oils could improve
the physical properties of beverage emulsions, including droplet size, size
distribution and turbidity, compared with only orange oil in oil phase of the
beverage emulsion. And the effect of long chain triglycerides on the physical
stabilities of beverage emulsions was significant (p<0.05) than that with medium
chain triglycerides (MCT). The oxidation rate of orange oil in the emulsion was
faster compared to that of the orange oil/carrier oils in emulsions. However, the
rheological properties of beverage emulsions were hardly dependent on the carrier
oils. In addition, all the emulsions exhibited near-Newtonian fluid behavior.
These findings revealed that the physicochemical properties of the beverage
emulsions could be effectively improved by the presence of carrier oils.
PMID- 28411992
TI - Improved oxidative barrier properties of emulsions stabilized by silica-polymer
microparticles for enhanced stability of encapsulants.
AB - The materials encapsulated within oil-in-water emulsions are prone to oxidation
due to the permeation of oxidative species across the oil-water interface and
into the lipid phase. Thus, the oxidative barrier properties of the interfacial
layer are pivotal in reducing oxidation within emulsified oils. To enhance these
barrier properties, we explored an approach of stabilizing emulsions using
'silica-polymer microparticles'. We hypothesize that these microparticles will
enhance the barrier properties of emulsion interfaces by mechanisms such as
higher interfacial thickness and quenching of oxidative species before they
permeate into the emulsions. Silica-epsilon-polylysine (Si-EPL) microparticles
were synthesized by electrostatic aggregation of anionic silica nanoparticles and
cationic epsilon-polylysine in the aqueous phase. Formation of Si-EPL
microparticles was validated using particle size, zeta-potential and scanning
electron microscopy measurements. These microparticles were subsequently used for
emulsion stabilization. Emulsions stabilized by silica nanoparticles alone were
used as control. Oxidative barrier properties were determined by measuring the
rate of permeation of peroxyl radicals from the aqueous to the oil phase of the
emulsion using fluorescence based methods. The rate of permeation of peroxyl
radicals was significantly lower in emulsions stabilized by Si-EPL microparticles
compared to that stabilized by silica nanoparticles. One of the mechanisms
responsible for the observed effect was enhanced quenching of peroxyl radical by
Si-EPL microparticles before they can permeate inside the oil phase. To further
validate the results, stability of a model bioactive compound, retinol,
encapsulated in these emulsions was compared. Consistent with peroxyl radical
permeation measurements, emulsion stabilized by Si-EPL microparticles
significantly improved the oxidative stability of retinol compared to that
stabilized by silica nanoparticles alone. Thus, by engineering the physical
properties of the interfacial layers, the oxidation of the encapsulants in
emulsions can be controlled.
PMID- 28411993
TI - Impact of irradiation and thermal processing on the immunochemical detection of
milk and egg allergens in foods.
AB - There is little information available on the antigenicity of allergens in foods
subjected to gamma irradiation and thermal processes. The objective of the study
was to evaluate the effects of gamma irradiation and thermal processing on the
recovery of milk and egg allergens in foods prepared using irradiated wheat flour
incurred with these allergens. Bread, boiled pasta and extruded cereal were
selected as food matrices for the study. Allergen detection was performed using
Surface Plasmon Resonance (SPR) and commercially available enzyme linked
immunosorbent assay (ELISA) kits. Protein structure was characterized using
differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)
spectroscopy, and circular dichroism (CD) spectroscopy. The ELISA kits performed
well in detecting allergens in the unprocessed flours with recoveries ranging
from 63-120%. The results for dough and uncooked pasta were similar to those of
unprocessed flours. Recoveries for boiled pasta were significantly (p<=0.05)
reduced. The lowest allergen recoveries were obtained in bread samples. Allergen
recoveries in gamma irradiated samples depended on the irradiation dose, the type
of ELISA kit used, the tested matrix, and the processing method. FTIR and CD
results showed that among the allergens casein was the most thermostable followed
by ovomucoid. beta-Lg and ovalbumin showed thermal sensitivity. In conclusion,
gamma irradiation may affect the antigenicity of allergenic food residues at low
levels depending on the food matrices and the processing methods.
PMID- 28411994
TI - Factors affecting the rheological properties of a structured cellular solid used
as a fat mimetic.
AB - The effects of water content, monoglyceride chain length and concentration, oil
type, and the addition of oil-phase and water-phase additives on the elastic
modulus and yield stress of a structured oil in water were evaluated. The goal
was to increase the elastic modulus of the original emulsion from 8.42*103+/
11.3Pa to 1.55*106+/-2.1*105Pa, and the yield stress from 112+/-2.31Pa to 835+/
227Pa. The addition of wax at greater than 10% (w/w), the use of palm oil or the
gelation of the liquid oil phase with 5-7.5% rice bran wax, the use of C-18
saturated monoglyceride at 6%(w/w), and 4% (w/w) for C-22 saturated monoglyceride
molecules were effective modifications capable of improving the mechanical
behavior of the emulsion so that it can be used as a zero trans and reduced
saturated fat laminating shortening substitute for puff pastry products.
PMID- 28411995
TI - The effect of in-amphorae aging on oenological parameters, phenolic profile and
volatile composition of Minutolo white wine.
AB - A wine was obtained from cryomacerated Minutolo grapes under reductive conditions
and aged for 12months in glass container and in 3 types of amphorae. After aging,
wines in glass containers showed the highest alcohol content, volatile acidity,
dissolved oxygen, concentrations of aromatics, alcohols, and esters and by the
lowest contents of enols and terpenes. They also showed the highest decrease of
flavonoids, hydroxycinnamoyl tartaric acids, and procyanidins. Wines in raw
amphorae showed the dramatic decrease of flavonoids and flavans reactive with
vanillin. The highest antioxidant activity was exhibited by wines in engobe
amphorae, while the lowest values were showed by the wines in glass containers
and glazed amphorae. Caftaric acid and procyanidin B3 decreased in wine aged
under glass while epicatechin mainly reduced in raw amphorae. According to the
Principal Component Analysis, the wines resulted homogeneously grouped as a
function of the type of container in which were aged.
PMID- 28411996
TI - Generation of volatile compounds in Brazilian low-sodium dry fermented sausages
containing blends of NaC1, KC1, and CaC12 during processing and storage.
AB - Brazilian dry fermented sausages with different salt contents were manufactured:
control (2.5% NaCl), 50% salt reduced (1.25% NaCl, F1), 50% replaced by KCl
(1.25% NaCl and 1.25% KCl, F2), 50% replaced by CaCl2 (1.25% NaCl and 1.25%
CaCl2, F3), and 50% replaced by KCl and CaCl2 (1.25% NaCl, 0.625% KCl and 0.625%
CaCl2, F4). Changes in the composition of volatile compounds were studied during
processing (0, 7, and 19days) and storage (30, 60, and 90days). Neither reduction
nor replacement of NaCl by KCI affected the volatile compounds produced during
the manufacturing process, and both increased the volatile compounds from
carbohydrate fermentation and amino acid degradation during storage. The addition
of CaCl2 improved the generation of hexanal and (E)-hept-2-enal and other
volatiles from lipid oxidation during processing and storage. After 90days of
storage, the control sample showed an increase in the generation of volatile
compounds from lipid oxidation.
PMID- 28411997
TI - Macromolecular antioxidants or non-extractable polyphenols in fruit and
vegetables: Intake in four European countries.
AB - Macromolecular antioxidants or non-extractable polyphenols are an emerging and
ignored fraction of dietary antioxidants that present differential structural and
physiological features as compared with the well-known extractable polyphenols.
In this study, the macromolecular antioxidant content and profile were determined
by the first time for the 24 most consumed fruit and vegetables in four European
countries (France, Germany, The Netherlands and Spain). Results showed that
macromolecular antioxidants, made up of hydolysable polyphenols and polymeric
proanthocyanidins, are major contributors (mean value 57%) to the total
polyphenol content of fruit and vegetables. Macromolecular antioxidant intake
from fruit and vegetable determined in the four countries selected was about
200mg. Spain had the highest daily per capita macromolecular antioxidant intake
from fruit, while The Netherlands had the highest intake derived from vegetables.
Future studies of plant food macromolecular antioxidant analysis and of dietary
intakes in different populations are needed to elucidate the contribution of
these macromolecular antioxidants to the health effects associated with fruit and
vegetable consumption, and with dietary antioxidant intake.
PMID- 28411998
TI - Social representations of safety in food services.
AB - This research aimed to evoke and analyze the perceptions of safe food through the
perspective of customers at two different food service settings in Sao Paulo,
Brazil. In-depth interviews (N=66) were conducted using a guide with open
questions focused on the individual's perceptions of safety, knowledge of food
borne diseases and self-involvement in the food chain. The Collective Subject
Discourse (CSD) technique, based on the Theory of Social Representations, was set
as the framework for the content analysis of the individual speeches with the aim
of writing a collective discourse representing the "voice of the customer".
Similarities and differences reflecting different socio-economic backgrounds came
up: in general, the interviewees showed concerns about hygiene and good practices
and recognized some food hazards, especially those of chemical and biological
natures. In situation of social vulnerability, some customers showed greater
concern with the guarantee of access to a substantial meal in face of economic
constraint. Finally, most customers reported a passive role in the food chain and
seemed to transfer to the restaurant staff the entire responsibility for the
safety of the meals served therein.
PMID- 28411999
TI - Impact of the industrial freezing process on selected vegetables - Part I.
Structure, texture and antioxidant capacity.
AB - In this work, the impact of the industrial freezing process on structure, texture
and total antioxidant capacity was studied using green asparagus stems, zucchini
and green beans. Samples were analysed as raw/uncooked, blanched, raw/boiled and
industrially frozen/boiled. A consistent damage of the vegetable tissue was
revealed by the histological analysis on vegetables boiled after freezing. The
cells appeared to be dehydrated, contracted and separated at different levels
depending on the anatomical structure of each vegetable. The initial textural
quality was partially retained in all blanched vegetables, and enhanced in cut
tested asparagus stems, in relation to the action of phenolic acids at cell wall
level. Raw/boiled and industrially frozen/boiled asparagus stems exhibited
comparable forces of penetration and cut tests. On the other hand, zucchini, both
raw and frozen, completely softened after boiling making the texture measurement
impossible. Industrially frozen/boiled green beans showed higher values of cut
and penetration forces, probably due to a higher presence of swollen cell walls,
in comparison to those raw/boiled. Blanching and boiling significantly increased
the ferric reducing antioxidant power values of asparagus stems and green beans
compared to uncooked/raw samples, while boiling after the freezing process
significantly deprived both vegetables of the initial antioxidant capacity. On
the other hand, boiling the frozen zucchini proved to be detrimental to the
antioxidant capacity. In conclusion, manufacturers and researchers should join
together to develop specific industrial freezing process conditions according to
the matrix of each vegetable.
PMID- 28412000
TI - Corrigendum to "Reliable estimation of dietary exposure to furan from coffee: An
automatic vending machine as a case study" [Food Research International 61 (2014)
257-263].
PMID- 28412001
TI - In vitro antioxidative and binding properties of phenolics in traditional, citrus
and exotic fruits.
AB - Many polyphenols bind proteins, therefore our research was focused on the
potential of protein binding to polyphenols of investigated fruits and their
health-related effects. The contents of polyphenols and related antioxidant
activities of traditional, citrus and exotic fruits were compared. The presence
of polyphenols (flavonoids and phenolic acids) in the investigated samples and
their interaction with human serum albumin (HSA) was studied by HPLC, Fourier
Transform Infrared (FT-IR) and three dimensional fluorescence spectroscopy (3D
FL). The highest levels of polyphenols, antioxidant and binding capacities were
found in red and blond grapefruits (citrus group), followed by strawberries and
apples (traditional group) and mangosteen and kiwi fruit (exotic fruit), which
also contained the highest levels of protocatechuic, p-coumaric, ferulic acids
and quercetin. In conclusion, for the first time, the interaction of the
polyphenols with human serum albumin was evaluated by fluorometry/FTIR. The
obtained binding profiles allowed the comparison of three different groups of
fruits. A mixture of these fruits can be recommended for consumption.
PMID- 28412002
TI - Yacon (Smallanthus sonchifolius) and Lactobacillus acidophilus CRL 1014 reduce
the early phases of colon carcinogenesis in male Wistar rats.
AB - The modifying effects of aqueous yacon extract (AYE) and Lactobacillus
acidophilus CRL 1014 against colon carcinogenesis induced by 1,2
dimethylhydrazine (DMH) in male Wistar rats were investigated. Animals were
allocated into five groups: G1: untreated group; G2: DMH-treated group; G3:
DMH+L. acidophilus-treated group; G4: DMH+AYE-treated group; G5: DMH+L.
acidophilus and AYE-treated group. A significant reduction (p<0.05) in leukocyte
DNA damage and in colonic cell proliferation was observed after the first DMH
administration in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. In
this moment, a significant increase (p<0.05) in colonic apoptosis was also
observed in G3 (probiotic) and G5 (synbiotic) groups. In special, at five months
after DMH administrations, a significant reduction (p<0.05) in ACF development
was observed in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups.
Incidence of colon tumors was lower at five months in G4 (prebiotic) and G5
(synbiotic) groups but not in eight months after DMH administrations. In
conclusion, the findings suggest that the oral treatments have potential effects
as a chemopreventive agent against colon carcinogenesis on an early stage of
tumor development.
PMID- 28412003
TI - Preparation, physicochemical characterization and release behavior of the
inclusion complex of trans-anethole and beta-cyclodextrin.
AB - Trans-anethole (AT) has a variety of antimicrobial properties and is widely used
as food functional ingredient. However, the applications of AT are limited due to
its low water solubility, strong odor and low physicochemical stability.
Therefore, the aim of this work was to encapsulate AT with beta-cyclodextrin
(beta-CD) for obtaining inclusion complex by co-precipitation method. The
measurements effectively confirmed the formation of inclusion complex between AT
and beta-CD. The results showed that the inclusion complex presented new solid
crystalline phases and was more thermally stable than the physical mixture and
beta-CD. The phase solubility study showed that the aqueous solubility of AT was
increased by being included in beta-CD. The calculated stability constant of
inclusion complex was 1195M-1, indicating the strong interaction between AT and
beta-CD. Furthermore, the release study suggested that beta-CD provided the
protection for AT against evaporation. The release behavior of AT from the
inclusion complex was controlled.
PMID- 28412004
TI - The use of active PET to package rose wine: Changes of aromatic profile by
chemical evolution and by transfers.
AB - Active Polyethylene Terephthalate (PET) bottles containing 1 or 3% of oxygen
scavenger (named 1osPET and 3osPET) were used to pack rose wine. Changes in the
aromatic profiles were monitored during 12months and compared to those of a wine
packed in glass bottles. Wine in 1osPET bottles was differentiated from wine in
glass or 3osPET bottles by ten aging markers such as cis-dioxane, ethyl pyruvate
or furfural. Only trans-1,3-dioxolane allowed to discriminate wine in glass and
in 3osPET bottles. Methionol, an oxygen sensitive aroma compound, was preserved
in glass and 3osPET bottles but was slightly degraded (15%) in 1osPET bottles.
Chemical reactions were the main cause of the aroma compound degradation. Indeed,
the total amount of compounds sorbed only reached 160MUg considering the bottles
and the joint of cap after 12months of storage. The use of PET with 3% of oxygen
scavenger is adapted to pack wine for at least 12months.
PMID- 28412005
TI - Assessing of the potential of extruded flour paste as fat replacer in O/W
emulsion: A rheological and microstructural study.
AB - Extruded flour represents an economical and environmental friendly alternative as
fat replacer. In this research, the potential use of an extruded flour-water
paste as fat replacer in an oil-in-water emulsion was studied. The effect of
flour-water ratio and level of oil replacement (30, 50 and 70%) on the
microstructure, rheological properties and stability of mayonnaise-like emulsion
was evaluated. Fat replacement by extruded flour gradually increased the number
and reduced the size of oil droplets. All the emulsion samples showed a
pseudoplastic behaviour. At low shear rates a Newtonian region characterised by
Carreau model appeared (R2>0.99). In general, the limiting viscosity of the
Newtonian region and the consistency index increased with the decreased water
content of the paste and increased the level of oil substitution. A decrease in
oil concentration led to a greater thixotropic behaviour. Oscillatory test
revealed that predominance of the continuous or dispersed phase influenced
viscoelastic behaviour. Reduction in oil content resulted in an increased freeze
thaw stability. Results suggested that if the flour-water ratio of the paste is
controlled, extruded flour is appropriate for preparing reduced-fat oil-in-water
emulsion with similar rheological properties to the full fat and greater freeze
thaw stability.
PMID- 28412006
TI - Identification of potent antioxidant bioactive peptides from goat milk proteins.
AB - Goat milk proteins have gained increasing attention especially the bioactive
peptides released from the parent proteins by digestive enzymes. Specifically,
the interest in bioactives of goat milk is intensifying due to its reduced
allergenicity compared to bovine milk. In this study, proteins of goat milk were
fractionated into caseins (GCP) and whey proteins (GWP), hydrolyzed by pepsin and
the generated peptides were examined for radical scavenging activities. The
hydrolysates of whey (P-GWP) and casein (P-GCP) proteins exhibited potent
superoxide anion (O2?-) scavenging activity in a dose-dependent manner, as
investigated using the natural xanthine/xanthine oxidase (X/XOD) system. The P
GWP and P-GCP dramatically quenched the O2?- flux but had negligible effect on
the catalytic function of the enzyme, indicating specificity to scavenge O2?- but
not oxidase inhibition. Further, both P-GWP and P-GCP were able to remarkably
quench the chemical DPPH radical. Fractionation of hydrolysates by size-exclusion
chromatography produced four fractions (F1-F4) from both hydrolysates, with
variable O2?- scavenging activities. However, the slow eluting fractions (F4) of
both hydrolysates and fast eluting fraction (F2) of P-GCP contained peptides with
the highest scavenging activities. Peptides in the active fractions of P-GWP and
P-GCP, isolated by reversed phase-HPLC, exhibited significantly strong O2?-
scavenging activities. MALDI-TOF-MS allowed the identification of several
antioxidant peptides derived from both caseins and whey proteins, with beta
casein and beta-lactoglobulin being the major contributors, respectively. The
results demonstrate that digestion with pepsin generates multiple soluble
peptides from goat milk protein fractions with remarkable ability to scavenge
superoxide radicals and thus providing a fascinating opportunity for their
potential candidacy as antioxidant bioactive peptides.
PMID- 28412007
TI - Volatile profiles of healthy and aflatoxin contaminated pistachios.
AB - The volatile profile of four different groups of dried pistachios namely: H:
healthy, NC: naturally contaminated with aflatoxin, AC: artificially contaminated
with aflatoxigenic strains of the fungi Aspergillus flavus and ANT: artificially
contaminated with non-toxigenic strains of the fungi A. flavus, was determined.
The volatiles were isolated by the HS-SPME method and determined by GC-FID and GC
MS, whereas aflatoxin by HPLC. Seventy two volatile compounds were identified
almost equally distributed among the above four studied groups. The predominant
chemical compounds were monoterpenes, alcohols, ketones, aldehydes, esters and
hydrocarbons. The monoterpenes, mainly determined as alpha-pinene and alpha
terpinolene were detected in all samples. Even though the general volatile
profile was similar among groups, some differences were detected between healthy
and contaminated groups of samples. When some key volatiles such as eight-carbon
and seven-carbon alcohols and aldehydes were used along with the species-specific
sesquiterpenes and the other terpenes detected, a correct classification was
obtained in H, NC, AC and ANT groups, as was demonstrated by cluster and
discriminant analyses. This evidence provides a potential tool for distinguishing
contaminated samples on the basis of characteristic volatile patterns.
PMID- 28412008
TI - Temperature-dependent structure stability and in vitro release of chitosan-coated
curcumin liposome.
AB - Liposome, a promising delivery system with phospholipid bilayer, could improve
the water solubility of curcumin, which is a polyphenolic natural product with
many bioactivities. However, the instability of liposome limits its development
in application. In this study, the chitosan was used to protect the structure
stability of phospholipid bilayer of curcumin liposome and control the sustained
release rate of curcumin further. The temperature stability and phase transition
were studied by differential scanning calorimetry. When curcumin molecule was
embedded in phospholipid bilayer, the pre-transition temperature (50.40 degrees
C) and main phase transition temperature (61.47 degrees C) decreased about 10
degrees C compared to it without curcumin, and phospholipid bilayer fluidity was
increased. The pre-transition temperature was disappeared after chitosan coated
on the surface of curcumin liposome. The thermal stability test and X-ray
diffraction also indicate that high temperature could change the structure of
liposome and chitosan could protect the curcumin from damage and leak. The in
vitro release study showed that the cumulative release rate got faster with
temperature increased and chitosan could decrease the release rate. These results
may guide the potential application of chitosan-coated liposome as a carrier of
curcumin in nutraceutical and functional foods.
PMID- 28412009
TI - Shockwave lithotripsy with music: Less painful and more satisfactory treatment.
AB - INTRODUCTION: The objective of this study was to determine whether listening to
music during a session of extracorporeal shockwave lithotripsy (ESWL) improves
patients' pain. MATERIAL AND METHOD: A simple, blind randomisation was undertaken
of patients with kidney and ureter stones attending an ESWL session of 7,000
waves for the first time, between September and December 2014. One group was
given music and the other was not. The age, gender, location of stones
(kidney/ureter) were recorded and 2questionnaires: pre ESWL (questionnaire A) and
postESWL (questionnaire B). Each questionnaire contained a question about anxiety
and another question on pain on the Likert scale (0-10). Questionnaire B also had
a question on satisfaction and comfort (Likert 0-10). Other variables included
heart rate, respiratory rate, systolic and diastolic blood pressure on wave
2,000, 5,000 and 7,000, reason for halting the procedure, total pethidine (mg),
secondary analgesia, energy (J) and frequency (Hz). Bivariate analysis using the
Student's t-test, X2/Fisher test and a multiple linear regression model. RESULTS:
The sample comprised 95 patients, with a mean age of 52 (+/-13) years, 35
(36.84%) females, 60 (63.2%) males. A total of 25 (26.3%) ureter stones and 70
(73.7%) kidney stones. A number of 42 (44.2%) patients were given music. There
were no differences between the demographic variables or questionnaire A scores.
Satisfaction and pain were better on questionnaire B with music. CONCLUSION:
Music can reduce pain and improve patient satisfaction in ESWL treatment. More
studies are required to confirm this effect.
PMID- 28412010
TI - Assessment of impact of urbanisation on background radiation exposure and human
health risk estimation in Kuala Lumpur, Malaysia.
AB - Kuala Lumpur has been undergoing rapid urbanisation process, mainly in
infrastructure development. The opening of new township and residential in former
tin mining areas, particularly in the heavy mineral- or tin-bearing alluvial soil
in Kuala Lumpur, is a contentious subject in land-use regulation. Construction
practices, i.e. reclamation and dredging in these areas are potential to enhance
the radioactivity levels of soil and subsequently, increase the existing
background gamma radiation levels. This situation is worsened with the
utilisation of tin tailings as construction materials apart from unavoidable soil
pollutions due to naturally occurring radioactive materials in construction
materials, e.g. granitic aggregate, cement and red clay brick. This study was
conducted to assess the urbanisation impacts on background gamma radiation in
Kuala Lumpur. The study found that the mean value of measured dose rate was 251+/
6nGyh-1 (156-392nGyh-1) and 4 times higher than the world average value. High
radioactivity levels of 238U (95+/-12Bqkg-1), 232Th (191+/-23Bqkg-1,) and 40K
(727+/-130Bqkg-1) in soil were identified as the major source of high radiation
exposure. Based on statistical ANOVA, t-test, and analyses of cumulative
probability distribution, this study has statistically verified the dose
enhancements in the background radiation. The effective dose was estimated to be
0.31+/-0.01mSvy-1 per man. The recommended ICRP reference level (1-20mSvy-1) is
applicable to the involved existing exposure situation in this study. The
estimated effective dose in this study is lower than the ICRP reference level and
too low to cause deterministic radiation effects. Nevertheless based on
estimations of lifetime radiation exposure risks, this study found that there was
small probability for individual in Kuala Lumpur being diagnosed with cancer and
dying of cancer.
PMID- 28412011
TI - [Nicolau livedoid dermatitis with severe neurological involvement in a child].
AB - BACKGROUND: Nicolau syndrome is a rare condition consisting in tissue ischemia
and necrosis following intramuscular, intra-articular or subcutaneous injection.
PATIENTS AND METHODS: Immediately after gluteal intramuscular injection of
benzathine-penicillin, a 10-year-old male child presented an extensive painful
violaceous lesion on the left buttock associated with urinary incontinence and
left lower-limb paresis. Additional underlying muscular damage was supported by
high serum levels of creatine kinase and lactate dehydrogenase. Treatment was
based on fluid expansion, intravenous steroids and anticoagulants, resulting in
improvement of cutaneous and muscular lesions. Improvement in terms of
neurological dysfunction was obtained after regular neuromuscular rehabilitation.
DISCUSSION: This case underlines the need to prevent Nicolau syndrome by means of
compliance with the technical recommendations for intramuscular injections.
PMID- 28412012
TI - Preliminary results for interval feeding the orthogonal pressurized planar
electrochromatography system with sample solution for its preparative separation.
AB - The orthogonal pressurized planar electrochromatography (OPPEC) is an example of
2-D separation technique, in which two simultaneous and orthogonal processes of
electrophoresis and chromatography are involved in the separation mechanism. In
the case of preparative separation of substances characterized by different
electrophoretic mobility, such separation system can be constantly fed with the
sample solution and the separated components can be constantly collected at its
outlet. In the paper, as opposed to the previous studies, we discuss the
capabilities of OPPEC technique for preparative separation of substances
characterized by the same electrophoretic mobility. According to the proposed
solution, the separation system can be periodically fed with the sample solution
and separated components can be collected alternately at its outlet. The
advantages of this new approach over the column chromatography with regard to the
separation of complex mixtures have been signaled.
PMID- 28412013
TI - Investigation of the imaging characteristics of the ALBIRA II small animal PET
system for 18F, 68Ga and 64Cu.
AB - AIM: In this study the performance characteristics of the Albira II PET sub
system and the response of the system for the following radionuclides 18F, 68Ga
and 64Cu was analyzed. MATERIALS AND METHODS: The Albira II tri-modal system
(Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET,
SPECT and CT. The PET sub-system uses single continuous crystal detectors of
lutetium yttrium orthosilicate (LYSO). The detector assembly consists of three
rings of 8 detector modules. The transaxial field of view (FOV) has a diameter of
80mm and the axial FOV is 148mm. A NEMA NU-4 image quality phantom (Data Spectrum
Corporation, Durham, USA) having five rods with diameters of 1, 2, 3, 4 and 5mm
and a uniform central region was used. Measurements with 18F, 68Ga and 64Cu were
performed in list mode acquisition over 10h. Data were reconstructed using a
maximum-likelihood expectation-maximization (MLEM) algorithm with iteration
numbers between 5 and 50. System sensitivity, count rate linearity, convergence
and recovery coefficients were analyzed. RESULTS: The sensitivities for the
entire FOV (non-NEMA method) for 18F, 68Ga and 64Cu were (3.78+/-0.05)%, (3.97+/
0.18)% and (3.79+/-0.37)%, respectively. The sensitivity based on the NEMA
protocol using the 22Na point source yielded (5.53+/-0.06)%. Dead-time corrected
true counts were linear for activities <=7MBq (18F and 68Ga) and <=17MBq (64Cu)
in the phantom. The radial, tangential and axial full widths at half maximum
(FWHMs) were 1.52, 1.47 and 1.48mm. Recovery coefficients for the uniform region
with a total activity of 8MBq in the phantom were (0.97+/-0.05), (0.98+/-0.06),
(0.98+/-0.06) for 18F, 68Ga and 64Cu, respectively. CONCLUSION: The Albira II pre
clinical PET system has an adequate sensitivity range and the system linearity is
suitable for the range of activities used for pre-clinical imaging. Overall, the
system showed a favorable image quality for pre-clinical applications.
PMID- 28412014
TI - Continuum-based DFN-consistent numerical framework for the simulation of oxygen
infiltration into fractured crystalline rocks.
AB - We present an enhanced continuum-based approach for the modelling of groundwater
flow coupled with reactive transport in crystalline fractured rocks. In the
proposed formulation, flow, transport and geochemical parameters are represented
onto a numerical grid using Discrete Fracture Network (DFN) derived parameters.
The geochemical reactions are further constrained by field observations of
mineral distribution. To illustrate how the approach can be used to include
physical and geochemical complexities into reactive transport calculations, we
have analysed the potential ingress of oxygenated glacial-meltwater in a
heterogeneous fractured rock using the Forsmark site (Sweden) as an example. The
results of high-performance reactive transport calculations show that, after a
quick oxygen penetration, steady state conditions are attained where abiotic
reactions (i.e. the dissolution of chlorite and the homogeneous oxidation of
aqueous iron(II) ions) counterbalance advective oxygen fluxes. The results show
that most of the chlorite becomes depleted in the highly conductive deformation
zones where higher mineral surface areas are available for reactions.
PMID- 28412015
TI - Managing sepsis: Electronic recognition, rapid response teams, and standardized
care save lives.
AB - PURPOSE: Sepsis can lead to poor outcomes when treatment is delayed or
inadequate. The purpose of this study was to evaluate outcomes after initiation
of a hospital-wide sepsis alert program. MATERIALS AND METHODS: Retrospective
review of patients >=18years treated for sepsis. RESULTS: There were 3917 sepsis
admissions: 1929 admissions before, and 1988 in the after phase. Mean age (57.3
vs. 57.1, p=0.94) and Charlson Comorbidity Scores (2.52 vs. 2.47, p=0.35) were
similar between groups. Multivariable analyses identified significant reductions
in the after phase for odds of death (OR 0.62, 95% CI 0.39-0.99, p=0.046), mean
intensive care unit LOS (2.12days before, 95%CI 1.97, 2.34; 1.95days after, 95%CI
1.75, 2.06; p<0.001), mean overall hospital LOS (11.7days before, 95% CI 10.9,
12.7days; 9.9days after, 95% CI 9.3, 10.6days, p<0.001), odds of mechanical
ventilation use (OR 0.62, 95% CI 0.39, 0.99, p=0.007), and total charges with a
savings of $7159 per sepsis admission (p=0.036). There was no reduction in
vasopressor use (OR 0.89, 95% CI 0.75, 0.1.06, p=0.18). CONCLUSION: A hospital
wide program utilizing electronic recognition and RRT intervention resulted in
improved outcomes in patients with sepsis.
PMID- 28412016
TI - Comment on, "On the influence of the electron dose-rate on the HRTEM image
contrast", by Juri Barthel, Markus Lentzen, Andreas Thust, ULTRAM12246 (2016),
http://dx.doi.org/10.1016/j.ultramic.2016.11.016.
PMID- 28412017
TI - The endocannabinoid system, a novel and key participant in acupuncture's multiple
beneficial effects.
AB - Acupuncture and its modified forms have been used to treat multiple medical
conditions, but whether the diverse effects of acupuncture are intrinsically
linked at the cellular and molecular level and how they might be connected have
yet to be determined. Recently, an emerging role for the endocannabinoid system
(ECS) in the regulation of a variety of physiological/pathological conditions has
been identified. Overlap between the biological and therapeutic effects induced
by ECS activation and acupuncture has facilitated investigations into the
participation of ECS in the acupuncture-induced beneficial effects, which have
shed light on the idea that the ECS may be a primary mediator and regulatory
factor of acupuncture's beneficial effects. This review seeks to provide a
comprehensive summary of the existing literature concerning the role of
endocannabinoid signaling in the various effects of acupuncture, and suggests a
novel notion that acupuncture may restore homeostasis under different
pathological conditions by regulating similar networks of signaling pathways,
resulting in the activation of different reaction cascades in specific tissues in
response to pathological insults.
PMID- 28412018
TI - Diffuse Carotid Arteriosclerosis and Stroke in a Patient With Schimke Immuno
osseous Dysplasia.
PMID- 28412019
TI - Renal function in relation to sodium intake: a quantitative review of the
literature.
AB - We undertook a quantitative literature review to search for evidence underpinning
current guidelines proposing a reduction of sodium intake to less than 2.4 g/d
for the management of chronic kidney disease. We searched PubMed for peer
reviewed articles published from January 1980 through May 2016. Two investigators
screened 5072 publications and extracted data from 36, including 11 cross
sectional and 5 longitudinal observational studies and 20 intervention trials.
Within-study effect sizes were pooled and standardized to a sodium gradient of
100 mmol/d by using inverse-variance weighted random effects models. Among cross
sectional studies, the pooled odds ratio for albuminuria was 1.23 (95% confidence
interval [CI], 0.92-1.64, P = 0.16), and the pooled mean difference in glomerular
filtration rate amounted to 8.5 ml/min (CI, -2.3 to 19.2 ml/min; P = 0.12). In
the cohort studies, the pooled relative risk of a renal endpoint was 1.08 (CI,
0.92-1.29; P = 0.35). In the intervention trials (median duration, 14 days
[range, 4-186 days]), the mean differences in estimated glomerular filtration
rate and albuminuria (high vs. low sodium intake) averaged 4.6 ml/min (CI, 3.4
5.8 ml/min; P < 0.0001) and 53% (CI, 21-84; P = 0.001), respectively. Cochran's Q
statistic indicated significant heterogeneity among cross-sectional studies for
both estimated glomerular filtration rate and albuminuria (P < 0.0001) and among
intervention trials for albuminuria (P = 0.04). In conclusion, there is no robust
evidence suggesting that long-term reduction of salt intake would prevent chronic
kidney disease or delay its progression. However, our current findings, which
were mainly obtained in people with slight renal impairment, cannot be
extrapolated to patients with moderate or severe chronic kidney disease.
PMID- 28412020
TI - Cardiac surgery in patients with congenital heart disease is associated with
acute kidney injury and the risk of chronic kidney disease.
AB - Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of
patients undergoing surgery for congenital heart disease. Here we determine if CS
AKI is associated with chronic kidney disease (CKD) in patients with congenital
heart disease. Using Danish regional population-based registries, our cohort
study included patients with congenital heart disease born between 1990-2010 with
first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in
and out-patient laboratory serum creatinine data, we identified individuals
fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique
personal identifier enabled unambiguous data linkage and virtually complete
follow-up. The cumulative incidences of CKD stages 2-5 according to presence of
CS-AKI were computed utilizing serum creatinine values and Pottel's formula.
Using Cox regression, the corresponding hazard ratios were computed, adjusting
for sex, age at first cardiac surgery, calendar period of surgery, and congenital
heart disease severity. Of 382 patients with congenital heart disease undergoing
cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow
up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS
AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3%
(1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8
(1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and
is associated with an increased risk for CKD.
PMID- 28412021
TI - Prediction and validation of the duration of hemodialysis sessions for the
treatment of acute ethylene glycol poisoning.
AB - The duration of hemodialysis (HD) sessions for the treatment of acute ethylene
glycol poisoning is dependent on concentration, the operational parameters used
during HD, and the presence and severity of metabolic acidosis. Ethylene glycol
assays are not readily available, potentially leading to undue extension or
premature termination of HD. We report a prediction model for the duration of
high-efficiency HD sessions based retrospectively on a cohort study of 26 cases
of acute ethylene glycol poisoning in 24 individuals treated by alcohol
dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD
for more than 14 days, and two died. In 19 cases, the mean ethylene glycol
elimination half-life during high-efficiency HD was 165 minutes (95% confidence
interval of 151-180 minutes). In a training set of 12 patients with acute
ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and
a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases
to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model
was then validated in a set of seven acute ethylene glycol poisonings. Thus, the
HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene
glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.
PMID- 28412022
TI - Acute kidney injury is associated with microvascular myocardial damage following
myocardial infarction.
AB - Acute kidney injury (AKI) is a frequent complication in patients with ST
elevation myocardial infarction (STEMI) treated by primary percutaneous coronary
intervention. However, the pathophysiology of AKI in this setting is complex and
goes beyond the administration of contrast media. Studies assessing the impact of
infarct characteristics on AKI are currently lacking. Therefore, we investigated
the association of AKI with myocardial as well as microvascular injury in an
initial total of 361 consecutive STEMI patients treated by primary percutaneous
coronary intervention. Of these, 318 patients were included in final analysis.
Serum creatinine was measured on admission as well as 24, 48, and 72 hours
thereafter with AKI defined as an increase in serum creatinine of 0.3 mg/dl or
more. Cardiac magnetic resonance (CMR) scans were performed in the first week
after infarction, with microvascular injury visualized by late gadolinium
enhancement CMR defined as any region of hypoenhancement within the hyperenhanced
area of infarction. Sixteen patients developed AKI. They showed significantly
lower left ventricular ejection fraction (45[interquartile range 40-52]% vs.
54[47-59]%), larger infarct size (21[15-35]% vs. 12[7-22]%) of left ventricular
myocardial mass, and more frequent microvascular injury (81 vs. 46%) than those
free of AKI. Meaningfully, in multivariate analysis including all CMR data,
microvascular injury was the sole independent predictor of AKI (odds ratio 6.74,
95% confidence interval of 1.49-30.43). Thus, among revascularized STEMI
patients, the presence of microvascular injury assessed by CMR was independently
associated with an increased risk of AKI. This suggests a potential
pathophysiological link between cardiac microvascular disease and renal injury
following STEMI.
PMID- 28412023
TI - Precise prediction of activators for the human constitutive androstane receptor
using structure-based three-dimensional quantitative structure-activity
relationship methods.
AB - The constitutive androstane receptor (CAR, NR1I3) regulates the expression of
numerous drug-metabolizing enzymes and transporters. The upregulation of various
enzymes, including CYP2B6, by CAR activators is a critical problem leading to
clinically severe drug-drug interactions (DDIs). To date, however, few effective
computational approaches for identifying CAR activators exist. In this study, we
aimed to develop three-dimensional quantitative structure-activity relationship
(3D-QSAR) models to predict the CAR activating potency of compounds emerging in
the drug-discovery process. Models were constructed using comparative molecular
field analysis (CoMFA) based on the molecular alignments of ligands binding to
CAR, which were obtained from ensemble ligand-docking using 28 compounds as a
training set. The CoMFA model, modified by adding a lipophilic parameter with
calculated logD7.4 (S+logD7.4), demonstrated statistically good predictive
ability (r2 = 0.99, q2 = 0.74). We also confirmed the excellent predictability of
the 3D-QSAR model for CAR activation (r2pred = 0.71) using seven compounds as a
test set for external validation. Collectively, our results indicate that the 3D
QSAR model developed in this study provides precise prediction of CAR activating
potency and, thus, should be useful for selecting drug candidates with minimized
DDI risk related to enzyme-induction in the early drug-discovery stage.
PMID- 28412024
TI - Prevalence of bacterial contamination in platelet concentrates at the National
Center of Blood Transfusion (Mexico).
AB - OBJECTIVES: Most common bacterial sepsis associated with transfusion is caused by
contaminated Platelet Concentrates (PC). The screening of PC to detect bacterial
contamination is obligatory in Mexico, and it is carried out in quality control
programs. In Mexico, the identification and molecular characterization of
bacterial contaminants to detect contamination sources have not been implemented
due to high costs; however, it is an actual current need. MATERIAL AND METHODS:
One hundred PC were randomly selected and microbiologically analyzed. This sample
size corresponds to 1% of the PC obtained by the National Center of Blood
Transfusion (NCBT) in Mexico City according to the Official Mexican Standard NOM
253-SSA1-2012. Additionally, molecular biology tests were implemented in order to
identify the possible contamination sources. RESULTS: Nine of the 100 PC analyzed
(9%) showed bacterial contamination; analysis of the nucleotide sequences
revealed the presence of characteristic microbiota from donor skin and soil.
Diverse clonal relationship between the strains was identified in Staphylococcus
epidermidis. CONCLUSION: Detection of contaminants associated with environmental
and skin flora, shows the need to implement measures in the process of
disinfecting skin at the site of phlebotomy and cleaning each of the areas
involved in blood collection.
PMID- 28412025
TI - The influence of chronic IL-6 exposure, in vivo, on rat Achilles tendon
extracellular matrix.
AB - When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and
collagen cross-linking. APAP also enhances the exercise-induced increase in
peritendinous levels of IL-6. Elevated levels of IL-6 are associated with
tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6
would alter tendon extracellular matrix (ECM). IL-6 (~3000pgml-1) was injected
(3dwk-1 for 8-wks) into the Achilles peritendinous region of male Wistar rats
(n=16) with the opposite leg serving as a sham. Fractional synthesis rates (FSR)
were determined using deuterium oxide. Collagen (hydroxyproline) and hydroxylysl
pyridinoline (HP) cross-linking were analyzed by HPLC. ECM and IL-6 related genes
were evaluated using qRT-PCR. Relative to sham, collagen (Col) 1a1 but not Col3a1
expression was suppressed (47%) in tendons exposed to IL-6 (p<0.05). Lysyl
oxidase (LOX) and MMP-1 expression were also reduced (37%) in IL-6 treated
tendons (p<0.05). Relative to sham the expression of MMP-2, -3, -9, and TIMP-1
were not altered by IL-6 treatment (p>0.05). Interleukin-6 receptor subunit beta
precursor (IL6st) was lower (16%) in IL-6 treated tendons when compared to sham
(p<0.05). Suppressor of cytokine signaling 3 (Socs3), signal transducer and
activator of transcription 3 (STAT3), and protein inhibitor of activated STAT 1
(Pias1) were not altered by IL-6 exposure (p>0.05). Neither collagen nor cross
linking content were altered by IL-6 (p>0.05). Additionally, IL-6 treatment did
not alter tendon FSR. Chronic treatment with physiologically relevant levels of
IL-6 suppresses expression of Col1a1 and LOX while also altering expression of
select MMPs but does not alter Achilles tendon collagen synthesis.
PMID- 28412026
TI - Primary bone sarcomas in patients over 40 years of age: A retrospective study
using data from the Bone Tumor Registry of Japan.
AB - BACKGROUND: Optimal treatments of patients aged >40 years with osteosarcoma and
Ewing sarcoma and of patients with other types of bone sarcoma have not yet been
established. METHODS: The clinical characteristics of 746 patients with primary
bone sarcomas aged >40 years listed in the nationwide tumor registry (Bone and
Soft Tissue Tumor Registry of Japan) were investigated. Patients with Ewing
sarcoma, conventional chondrosarcoma, multiple myeloma, and malignant lymphoma
were excluded. The effects of adjuvant chemotherapy were determined by comparing
outcomes in patients aged 40-70 years with non-metastatic high grade bone tumors
who received surgery plus chemotherapy with those who underwent surgery alone.
RESULTS: Axial site tumors (38.6%) and distant metastasis at presentation (21.4%)
were frequent in patients aged >40 years with primary bone sarcomas. Chemotherapy
was administered to 407 (54.6%) patients. Their 5-year overall survival (OS) and
progression free survival (PFS) rates were 47.6% and 39.8%, respectively.
Multivariate analysis showed that distant metastases at presentation,
histological high grade, and radiation therapy were significantly correlated with
both OS and PFS. Age and tumor size were also significantly correlated with OS.
Patients aged 40-70 years who underwent surgery plus chemotherapy and those who
underwent surgery alone had 5-year OS rates of 69.3% and 63.2%, respectively (p =
0.092), and 5-year PFS rates of 55.4% and 50.7%, respectively (p = 0.63).
CONCLUSIONS: Bone sarcoma patients aged >40 years had distinct clinical features
and a poor prognosis. Chemotherapy did not improve OS or PFS in patients aged 40
70 years.
PMID- 28412027
TI - Regionalization of radical cystectomy in the United States.
AB - PURPOSE: Radical cystectomy (RC) has become increasingly regionalized to high
volume hospitals. Our objective was to describe changes in regional market
concentration and the distribution of RCs among hospitals, and examine how these
changes affect patient travel distance to surgery. MATERIALS AND METHODS: We used
the surveillance, epidemiology, and end results-Medicare database to identify
patients who had RC for bladder cancer from 2001 to 2011. We defined RC market
concentration within each Hospital Referral Regions (HRR) in surveillance,
epidemiology, and end results using the Hirschman-Herfindhal Index. We measured
straight-line patient travel distance to the nearest cystectomy provider hospital
and used linear regression to evaluate the effect of market concentration on
travel distance for surgery. We performed a similar analysis on patients who had
laparoscopic cholecystectomy as a comparator. RESULTS: We identified 10,802
patients with bladder cancer who had RC. From 2001 to 2011, 40% of HRRs had a
statistically significant increase in Hirschman-Herfindhal Index, 53% had no
significant change and 7% had a statically significant decrease. The median
patient travel distance increased significantly from 10.4 miles (interquartile
range: 2.6-30.2) to 16 miles (interquartile range: 6.3-40.4, P<0.0001). Patients
who lived in a highly concentrated HRR had to travel significantly further than
patients who lived in an unconcentrated HRR (beta = 37.5, P<0.001). These trends
were not seen for laparoscopic cholecystectomy. CONCLUSIONS: Between 2001 and
2011, RC became increasingly regionalized to a small group of hospitals with a
resultant increase in regional RC market concentration and patient travel
distance. The clinical consequences on these changes to patients who require RC
are uncertain.
PMID- 28412028
TI - [Effectiveness of erlotinib in Critical Care Unit in patients with non-small cell
lung cancer with EGFR mutation].
AB - INTRODUCTION: The search for mutations epidermal growth factor receptor (EGFR)
has changed the therapeutic approach and prognosis of non-small cell lung cancer
(NSCLC). The effectiveness of tyrosine kinase inhibitors (TKI) has been
demonstrated orally in patients with EGFR mutation. We report the case of a
patient for whom treatment with TKI was started effectively in a Critical Care
Unit. OBSERVATION: A patient of 59 years is followed for a stage IV lung
adenocarcinoma with metastases in liver, brain, adrenal, lung and pleura. After a
first course of chemotherapy (cisplatin-gemcitabine), the patient presents a
multi-factorial acute respiratory distress. Due to an EGFR mutation, transfer to
intensive care is decided then orotracheal intubation with mechanical
ventilation. It is decided to initiate treatment with erlotinib via nasogastric
tube. The evolution will be marked by a tumor response leading to a favorable
issue. CONCLUSIONS: This case shows the value of initiate TKI despite
hospitalization in Intensive Care Unit and highlights the question of the
transfer in ICU patients with EGFR mutation.
PMID- 28412029
TI - What's in a side effect? The association between pulmonary vasodilator adverse
drug events and clinical outcomes in patients with pulmonary arterial
hypertension.
AB - BACKGROUND: Adverse drug events (ADEs) with pulmonary vasodilator use in
pulmonary arterial hypertension (PAH) are common. ADEs may contribute to worse
quality of life; however, their relationship to prognosis is unknown. The
objective of this study was to determine whether common ADEs after initiating
subcutaneous treprostinil were associated with prognosis in PAH. METHODS: We
assembled a retrospective cohort of participants from four clinical trials of
treprostinil for PAH, including 908 participants who received subcutaneous
treprostinil and 243 who received placebo at the time ADEs were ascertained. The
occurrences of four common early ADEs (infusion reactions, headaches, jaw pain,
or gastrointestinal side effects) were assessed during the eight weeks after
starting the infusion. We used Cox proportional hazards to estimate associations
between ADEs and mortality. RESULTS: No ADEs related to placebo were associated
with mortality. In participants who received treprostinil, infusion reactions,
headaches, and jaw pain were not associated with mortality. Gastrointestinal side
effects occurring during the first eight weeks following treprostinil infusion
were associated with a 57% increase in the hazard of mortality (95% CI: 14-118%).
This relationship was unchanged after adjusting for demographic differences and
differences in baseline PAH severity. CONCLUSIONS: Gastrointestinal ADEs after
starting subcutaneous treprostinil were associated with an increased risk for
mortality. Increased mortality was not observed with other early ADEs or with
gastrointestinal symptoms in participants who were not receiving treprostinil at
the time. This hypothesis-generating association suggests ADEs may identify
different phenotypes in PAH.
PMID- 28412030
TI - Simple quantification method for N-nitrosamines in atmospheric particulates based
on facile pretreatment and GC-MS/MS.
AB - Nine N-nitrosamines (i.e., N-nitrosomethylamine, N-nitrosodiethylamine (NDEA), N
nitrosodimethylamine (NDMA), N-nitrosodi-n-propylamine (NDPA), N
nitrosomorpholine (NMor), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine
(NPip), N-nitorosodi-n-butylamine (NDBA), and N-nitrosodiphenylamine (NDPhA) in
atmospheric PM2.5 collected in the fall season from an roadside site and a
residential in Seoul, Korea have been analyzed using a newly developed method
consisting of simple direct liquid extraction assisted by ultrasonication and
subsequent quantification using a gas chromatography-triple quadrupole mass
spectrometry (GC-TQMS). Excellent recovery values (92-100%) and method detection
limits for the target compounds atmospheric PM samples could be achieved even
without an evaporation step for sample concentration. The concentration of total
N-nitrosamines in PM2.5 was ranged from 0.3 to 9.4 ng m-3 in this study; NDMA,
NDEA, NDBA, NPyr, and NMor in PM2.5 were found to be the most frequently
encountered compounds at the sampling sites. Since no industrial plant is located
in Seoul, vehicle exhausts were considered major cause of the formation of
nitrosamines in this study. The mechanisms how these compounds are formed and
detected in the atmosphere are explained from the viewpoint of secondary organic
aerosol. Considering the concentrations of N-nitrosamines and their associated
potential health risks, a systematic monitoring of nitrosamines present in both
ambient air and PM2.5 including seasonal and diurnal variations of selected sites
(including potential precursor sources) should be carried out in the future. The
proposed sample pretreatment method along with the analytical method will
definitely help us perform the monitoring study.
PMID- 28412031
TI - Alterations in hyolaryngeal elevation after esophageal anastomosis: A possible
mechanism for airway aspiration.
AB - AIM: A prospective study was performed to evaluate anatomical alterations and
hyolaryngeal elevation (HE) by videofluoroscopic swallowing study (VFSS) in
patients with esophageal atresia-tracheoesophageal fistula (EA-TEF). METHODS:
Patients operated for EA-TEF were evaluated for age, sex, type of atresia and
time to esophageal anastomosis. All patients were evaluated by videofluoroscopic
swallowing study (VFSS). Penetration-Aspiration scale (PAS>=7 is considered as
aspiration), distance between upper esophageal sphincter and 2nd cervical
vertebrae (UES-C2) and hyolaryngeal elevation (HE) were evaluated by the same
deglutitionist who was blind to the study. The results of EA-TEF patients were
compared with healthy children. RESULTS: Eighteen patients with EA-TEF and 10
healthy controls were included. The median age was 16months (12-36m) in EA-TEF
and 18months (13-51m) in controls. Male-to-female ratio was 5:4 and 4:1
respectively. 12 of cases were isolated-EA, 1 of them was EA-proximal TEF and 5
of the cases were EA-distal TEF. Half of the cases had primary EAN and others
underwent delayed esophageal repair. Early oral feeding was also started in 9
patients (50%) whereas others had delayed oral feeding. VFSS showed aspiration in
27.7 (n=5) of cases (PAS>=7) in EA group. The median distance between UES-C2 was
3.04cm (min: 2.17-max: 3.94) in EA and 4.17cm (min: 3.45-max: 6.24cm) in
controls. Median distance for HE was 0.37cm (min: 0.18-max: 1.1cm) in EA and 1.15
(min: 0.61-max: 1.06cm) in controls. The distance between UES-C2 was
significantly lower than controls (p<0.05) and HE was decreased in EA-TEF without
any statistical significance. CONCLUSION: Children with EA-TEF had shortened
distance between airway and upper esophagus. HE may be inefficient to protect
airway during deglutition. Anatomical alterations after EAN suggest that airway
problems may be related with decreased HE in children with EATEF. LEVEL OF
EVIDENCE: Level II (Development of diagnostic criteria in a consecutive series of
patients and a universally applied "gold standard").
PMID- 28412032
TI - Upregulation of MiR-369-3p suppresses cell migration and proliferation by
targeting SOX4 in Hirschsprung's disease.
AB - BACKGROUND: Hirschsprung disease (HSCR) is a congenital digestive disease in the
new born. miR-369-3p has been reported to be involved in many human diseases.
However, the relationship between miR-369-3p and HSCR remains largely unknown.
METHODS: In this study, qRT-PCR was used to detect the relative expression of miR
369-3p in 60 HSCR bowel tissue samples and 47 matched controls. Bioinformatic
analysis and dual-luciferase reporter assay were performed to evaluate the target
for miR-369-3p. Cell Counting Kit-8 (CCK-8) assay, Transwell assay, wound healing
assay and flow cytometry were employed to investigate the biological function of
miR-369-3p in human SH-SY5Y and 293T cell lines. RESULTS: We found that ganglion
cell numbers were remarkably reduced while miR-369-3p was significantly
upregulated in HSCR tissues compared to that in adjacent normal tissues (P<0.01).
Dual-luciferase reporter assay showed that the 3'-UTR of SOX4 was a direct target
to miR-369-3p. Moreover, an increased level of miR-369-3p was inversely
correlated with decreased levels of SOX4 mRNA and protein (P<0.05, respectively).
Dysregulation of miR-369-3p and SOX4 significantly suppressed cell proliferation
and migration in SH-SY5Y and 293T cell lines in vitro (P<0.05, respectively).
CONCLUSION: Our study demonstrates that aberrant expression of miR-369-3p might
play a crucial role in the development HSCR by regulating SOX4 expression, which
may infer that it is an effective diagnostic target in the pathogenesis of HSCR,
but investigation is still needed to explore the underlying mechanism.
PMID- 28412033
TI - Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of
diabetic nephropathy in a mouse model of type 2 diabetes.
AB - AIMS: Vasopressin is increased in diabetes and was shown to contribute to
development of diabetic nephropathy through V2 receptor (V2R) activation in an
experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains
undocumented. This study addresses the issue in a mouse model of type 2 diabetes.
METHODS: Male obese diabetic db/db mice were treated for 12weeks with a selective
V2R antagonist (SR121463) and compared to non-treated db/db and non-diabetic db/m
mice. All animals were previously uninephrectomized. RESULTS: The V2R antagonist
did not alter glycemia or glycosuria in db/db mice. It induced a two-fold
increase in urine output and a 52% decrease in urine osmolality compared to non
treated db/db mice. After four weeks of treatment urinary albumin to creatinine
ratio was 50% lower in treated mice compared to non-treated mice, and remained
significantly lower until end of experiment. Glomerular filtration rate increased
significantly over time in non-treated db/db mice but remained stable in treated
mice. CONCLUSIONS: This study shows that vasopressin contributes to albuminuria
and glomerular hyperfiltration via V2R in a mouse model of type 2 diabetes. It
documents causality behind the association of vasopressin with renal disease
observed in diabetic patients.
PMID- 28412034
TI - Reply to: A systematic review of complications associated with direct implants
vs. tissue expanders following wise pattern skin-sparing mastectomy.
PMID- 28412035
TI - Novel Consequences of Bird Pollination for Plant Mating.
AB - Pollinator behaviour has profound effects on plant mating. Pollinators are
predicted to minimise energetic costs during foraging bouts by moving between
nearby flowers. However, a review of plant mating system studies reveals a
mismatch between behavioural predictions and pollen-mediated gene dispersal in
bird-pollinated plants. Paternal diversity of these plants is twice that of
plants pollinated solely by insects. Comparison with the behaviour of other
pollinator groups suggests that birds promote pollen dispersal through a
combination of high mobility, limited grooming, and intra- and interspecies
aggression. Future opportunities to test these predictions include seed paternity
assignment following pollinator exclusion experiments, single pollen grain
genotyping, new tracking technologies for small pollinators, and motion-triggered
cameras and ethological experimentation for quantifying pollinator behaviour.
PMID- 28412036
TI - RNA-Binding Proteins Revisited - The Emerging Arabidopsis mRNA Interactome.
AB - RNA-protein interaction is an important checkpoint to tune gene expression at the
RNA level. Global identification of proteins binding in vivo to mRNA has been
possible through interactome capture - where proteins are fixed to target RNAs by
UV crosslinking and purified through affinity capture of polyadenylated RNA. In
Arabidopsis over 500 RNA-binding proteins (RBPs) enriched in UV-crosslinked
samples have been identified. As in mammals and yeast, the mRNA interactomes came
with a few surprises. For example, a plethora of the proteins caught on RNA had
not previously been linked to RNA-mediated processes, for example proteins of
intermediary metabolism. Thus, the studies provide unprecedented insights into
the composition of the mRNA interactome, highlighting the complexity of RNA
mediated processes.
PMID- 28412037
TI - Relationship between the degree of perineal trauma at vaginal birth and change in
haemoglobin concentration.
AB - BACKGROUND: Postpartum anaemia is a problem with high prevalence that
significantly affects maternal recovery. Among the causal factors is perineal
trauma. However, it is still not known what degree of perineal trauma produces a
greater reduction of haemoglobin. AIM: To assess the relationship between the
degree of perineal trauma and change in haemoglobin concentration at vaginal
birth. METHODS: An observational, analytical retrospective cohort study was
performed at the Mancha-Centro Hospital (Spain) during the period 2010-2014. Data
were collected regarding 3479 women who gave birth vaginally. The main outcome
variable was the change in haemoglobin concentration. Multivariate analysis by
means of multiple linear regression was performed to control possible confounding
factors and to determine the net effect of each degree of perineal trauma on
haemoglobin reduction. FINDINGS: Of the total sample, 20.1% of women (699) had an
intact perineum, 41.6% (1446) experienced some form of perineal trauma, but not
episiotomy, and the remaining 38.3% of women (1334) underwent an episiotomy. The
average reduction of haemoglobin was 1.46g/dL (Standard Deviation (SD)=1.09g/dL)
for women without episiotomy with a second degree tear and 2.07g/dL (SD=1.24g/dL)
for women who had an episiotomy and no perineal tear. The greatest reduction
occurred among women with episiotomy and a third or fourth degree tear with a
decrease of 3.10g/dL (SD=1.32g/dL). CONCLUSION: Episiotomy is related to greater
reduction of haemoglobin concentration in comparison with all degrees of
spontaneous perineal trauma. The use of episiotomy should be strictly limited.
PMID- 28412038
TI - Surgical treatment of postintubation tracheal stenosis: A retrospective 22
patient series from a single center.
AB - BACKGROUND/OBJECTIVE: We aimed to present cases of postintubation tracheal
stenosis (PITS), all due to long-term intubation and treated surgically in a
university hospital, and to discuss them in light of the literature. METHODS: In
this retrospective study, 22 patients who were treated with tracheal resection
and reconstruction due to PITS were included. Demographics, intubation
characteristics, localization of stenosis, surgical technique and material,
postoperative complications, and survival of patients were recorded. RESULTS: The
mean intubation duration was 16.95 days with a median of 15.00 days. Collar
incision was applied in 19 cases (86.4%); in two cases (9.1%) a median sternotomy
incision was used; and in the remaining case (4.5%), a right thoracotomy incision
was made. The mean tracheal stenosis length was 2.14 cm (mean excision length,
2.5 cm). In 17 cases (77.3%), the anterior walls were supported with vicryl
(polyglactin) suture one by one. No postoperative complications were observed in
12 cases (54.5%). No recurrence developed during the long-term follow-up of 15 of
the 22 patients (68.2%). Two patients (9.1%) died in the early stages after
surgery, and five patients (22.7%) had a stent inserted due to restenosis.
CONCLUSION: Tracheal resection and end-to-end anastomosis are the most efficient
techniques in cases without medical contraindications, despite emerging stent or
endoscopic procedures. Endoscopic interventions can be suggested as an
alternative to surgery in patients for whom surgery cannot be performed or who
develop recurrence.
PMID- 28412039
TI - Distal left main trifurcation disease in a patient with porcelain aorta.
AB - Coronary trifurcation lesions are a complex subset of lesions and are
substantially more complex than bifurcations when treated with percutaneous
coronary intervention (PCI) because of higher rates of acute periprocedural
complications (dissection, myocardial infarction, acute vessel closure) and less
effective long-term outcomes (stent thrombosis, restenosis) as compared to non
bifurcation lesions. We present the case of a 73-year-old man who was admitted to
our hospital with symptomatic severe aortic stenosis who was found to have a
distal left main trifurcation disease as well as porcelain aorta on work-up.
Given the high risk of stroke during surgical aortic valve replacement and
coronary artery bypass grafting, the patient was accepted by the heart team to
proceed with percutaneous coronary intervention (PCI) and trans-catheter aortic
valve replacement (TAVR). We describe a successful double mini-crush stenting
technique approach for this case.
PMID- 28412040
TI - ROS formation is a differential contributory factor to the fungicidal action of
Amphotericin B and Micafungin in Candida albicans.
AB - The hypothetical role played by the intracellular formation of reactive oxygen
species (ROS) in the fungicidal action carried out by Amphotericin B (AmB) and
Micafungin (MF) was examined in Candida albicans, which remains the most
prevalent fungal pathogen. The clinical MICs for MF and AmB were 0.016 and
0.12MUg/ml, respectively. Whereas AmB (0.5-1.0*MIC) induced a marked production
of intracellular ROS accompanied by a high degree of cell killing in the C.
albicans SC5314 strain, the fungicidal effect of MF was still operative, but ROS
generation was slight. Preincubation with thiourea suppressed the formation of
ROS and caused a marked increase in cell viability, regardless of the antifungal
used. Simultaneous measurement of several well established antioxidant enzymes
(catalase, glutathione reductase and superoxide dismutase) revealed strong AmB
induced activation of the three enzymatic activities, whereas MF only had a weak
stimulating effect. Likewise, AmB but not MF promoted a conspicuous rise in the
mitochondrial membrane potential together with the intracellular synthesis of
trehalose, the non-reducing disaccharide which acts as a specific protector
against oxidative stress in C. albicans. Optical and electronic microscopy
analysis revealed a significant damage to cell integrity and structural
alterations caused by both antifungals. Taken together, our results strongly
suggest that the induction of an internal oxidative stress in C. albicans through
the accumulation of ROS is a preferential contributory factor to the antifungal
action of a widely used polyene (AmB) but not of MF (echinocandin).
PMID- 28412042
TI - Targeting the Prostacyclin Pathway: Beyond Pulmonary Arterial Hypertension.
AB - Pioneering work demonstrated that an unstable substance isolated from rabbit and
pig aortas could relax arterial smooth muscle and inhibit platelet aggregation.
Since then, prostacyclin (prostaglandin I2, PGI2) and its analogs have raised
much pharmacological interest. In this review we detail how the PGI2 signaling
pathway is much more complex than was initially anticipated, involving peroxisome
proliferator-activated receptors (PPARs), prostaglandin transporters (PGTs), and
PGI2-thromboxane A2 (TXA2) receptor (IP TP) heterodimerization. We discuss the
distinct affinities of PGI2 analogs for prostanoid receptors. In addition, we
introduce the new direct and indirect pharmacological approaches to targeting the
PGI2 pathway within the systemic circulation, including non-prostanoid agonists
of the prostacyclin receptor (IP) and PGT inhibitors, as well as transcutaneous
pathways using iontophoresis and nanostructured lipid carriers.
PMID- 28412041
TI - Targeting Tyrosine Phosphatases: Time to End the Stigma.
AB - Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for
numerous cellular processes, and several PTPs have been validated as therapeutic
targets for human diseases. Historically, the development of drugs targeting PTPs
has been highly challenging, leading to stigmatization of these enzymes as
undruggable targets. Despite these difficulties, efforts to drug PTPs have
persisted, and recent years have seen an influx of new probes providing
opportunities for biological examination of old and new PTP targets. Here we
discuss progress towards drugging PTPs with special emphasis on the development
of selective probes with biological activity. We describe the development of new
small-molecule orthosteric, allosteric, and oligomerization-inhibiting PTP
inhibitors and discuss new studies targeting the receptor PTP (RPTP) subfamily
with biologics.
PMID- 28412043
TI - Assessment of high-priced systemic antifungal prescriptions.
AB - OBJECTIVES: To assess compliance with international guidelines for costly
antifungal prescriptions and to compare these results with a first study
performed in 2007. METHODS: Retrospective study including all costly antifungal
prescriptions made in surgical and medical intensive care units and in a
hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were
assessed in terms of indication, dosage, and antifungal de-escalation. RESULTS:
Seventy-four treatments were analyzed. Treatments were prescribed for
prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%).
Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%)
and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable
in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%,
and inappropriate in 23%. Prescriptions were inappropriate for the following
reasons: lack of dosage adjustment in light of the hepatic function (10 cases),
underdosage or excessive dosage by>25% of the recommended dose in seven cases. De
escalation to fluconazole was implemented in 40% of patients presenting with a
fluconazole-susceptible candidiasis. CONCLUSION: The overall incidence of
appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively,
P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in
particular for empirical therapy, dosage adjustment, and potential de-escalation
to fluconazole.
PMID- 28412044
TI - Guidelines on the management of infectious encephalitis in adults.
PMID- 28412045
TI - Transcranial direct current stimulation (tDCS) as a treatment for visual
hallucinations: A case study.
PMID- 28412046
TI - The epigenetic mechanism for discordance of autoimmunity in monozygotic twins.
AB - Monozygotic twins share an identical DNA sequence but are not truly "identical".
In fact, when it comes to health and disease, they may often display some level
of phenotypic discordance. The cause of this discordance is often unknown.
Epigenetic modifications such as DNA methylation, histone modification, and
microRNAs-mediated regulation regulate gene expression and are sensitive to
external stimuli. These modifications may be seen to bridge the gap between
genetics and the environment. Over the years, the importance of epigenetics as a
primary mechanism for the role that the environment plays in defining phenotype
has been increasingly appreciated. Mechanisms of epigenetics include DNA
methylation, histone modifications and microRNAs. Discordance rates in
monozygotic twins vary depending on the specific condition, from 11% in SLE to
64% in psoriasis and 77% in PBC. Other autoimmune diseases in which discordance
is found among monozygotic twins has also been studied include type 1 diabetes,
multiple sclerosis, rheumatoid arthritis, dermatomyositis and systemic sclerosis.
In some cases, the differences in various epigenetic modifications is slight,
even though the concordance rate is low, suggesting that epigenetics is not the
only factor that needs to be considered. Nonetheless, the study of phenotypic
discordance in monozygotic twins may shed light on the pathogenesis of autoimmune
diseases and contribute to the development of new methodologies for the diagnosis
and treatment of these diseases.
PMID- 28412047
TI - Patient-reported Quality of Life After Proton Beam Therapy for Prostate Cancer:
The Effect of Prostate Size.
AB - BACKGROUND: In the present study, we assessed the effect of prostate gland size
on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL)
after definitive treatment of prostate adenocarcinoma with proton beam therapy.
PATIENTS AND METHODS: As a part of a prospective outcome tracking protocol, 81
patients treated at a single center between with proton beam therapy completed
the Expanded Prostate Cancer Index Composite (EPIC) questionnaire before
treatment and at the follow-up examinations. We reviewed the dosimetric data,
reported as Vx (volume of organ receiving x Gy), and patient-reported QOL at 6
months. Genitourinary QOL was assessed using the American Urological Association
symptom score and EPIC urinary domain score. GI QOL was assessed using the EPIC
GI domain score. RESULTS: Larger prostate glands were associated with greater
bladder V70 (P < .01) and rectal V70 (P < .01). The rectal V70 was < 15% for all
patients (range, 4%-13.8%) with the planned treatment volume coverage (percentage
of the prescription dose covering 95% of the volume > 95%) maintained. Patients
with larger prostates did not have a greater change in their American Urological
Association symptom index scores (< 30 cm3, +2.3; 30-49 cm3, +3.2; >= 50 cm3,
0.2; P = .06) or urinary domain score (< 30 cm3, -3.6; 30-49 cm3, -3.1; >= 50
cm3, +3.8; P = .76) at 6 months after treatment. Also, prostate size was not
associated with a change in the EPIC GI domain score at 6 months after treatment
(< 30 cm3, -3.7; 30-49 cm3, -1.1; >= 50 cm3, -0.55; P = .67). CONCLUSION:
Definitive proton beam therapy for prostate cancer to a dose of 79.2 Gy resulted
in excellent patient-reported urinary and GI QOL, independently of the baseline
prostate size. This single-institution finding should be tested further in a
multi-institutional study to confirm the potential limited role of androgen
deprivation therapy.
PMID- 28412048
TI - Comparative proteome profiling of hydatid fluid from Algerian patients reveals
cyst location-related variation in Echinococcus granulosus.
AB - Human cystic echinococcosis, an endemic zoonosis in Algeria, is caused by larvae
of the cestode Echinococcus granulosus. Parasitic modulation of the immune
response allows E. granulosus to persist in intermediate hosts. Previous in vitro
and in vivo immunological studies have shown differences in host immune responses
according to the status and location of the hydatid cysts in the body. In this
study, a proteomic analysis of human hydatid fluids was performed to identify the
proteins in hydatid cyst fluids. Hydatid fluid was obtained after cystic surgical
removal from three patients with these cysts. The study was conducted on fertile
hydatid fluids from lungs, vertebra, and infertile paravertebral fluids.
Comparisons of the protein compositions of these fluids revealed differences in
their protein profiles. These differences are probably related to the cyst
location and fertility status of the parasite. Notably, our analysis identified
new proteins from the parasite and human host. The identification of host
proteins in hydatid fluids indicates that the hydatid walls are permeable
allowing a high protein exchange rate between the metacestode and the affected
tissue. Interestingly, our study also revealed that parasite antigenic protein
expression variations reflect the differences observed in host immunostimulation.
PMID- 28412050
TI - [The correlation among the Ramsay sedation scale, Richmond agitation sedation
scale and Riker sedation agitation scale during midazolam-remifentanil sedation].
AB - BACKGROUND AND OBJECTIVES: Sedative and analgesic treatment administered to
critically ill patients need to be regularly assessed to ensure that previously
stated goals are well achieved as the risk of complications of oversedation is
minimized. We revised and prospectively tested the Ramsay Sedation Scale (RSS)
for interrater reliability and compared it with the Riker Sedation-Agitation
Scale (RSAS) and the Richmond Agitation Sedation Scale (RASS) to test construct
validity during midazolam-remifentanil sedation. METHODS: A convenience sample of
ICU patients was simultaneously and independently examined by pairs of trained
evaluators by using the revised RSAS, RSS, and RASS. Ninety-two ICU patients were
examined a total of 276 times by evaluator pairs. RESULTS: The mean patient age
was 61.32+/-18.68years, 45,7% were female (n=42), 54.3% male (n=50). Their APACHE
values varied between 3 and 39 with an average of 13.27+/-7.86 and 75% of the
cases were under mechanical ventilation. When classified by using RSS (2.70+/
1.28), 10.9% were anxious or agitated (RSS1), 68.5% were calm (RSS 2-3), and
20.6% were sedated (RSS 4-6). When classified by using RASS (-0.64+/-1.58), 20.7%
were anxious or agitated (RASS+1 to +4), 63.0% were calm (RASS 0 to -2), and
16.3% were sedated (RASS -3 to -5). When classified by using RSAS (2.63+/-1.00),
12% were anxious or agitated (RSAS 5-7), 57.6% were calm (RSAS 4), and 30.4% were
sedated (RSAS 1-3). RSS was correlated with the RSAS (r=-0.656, p<0.001) and RASS
was correlated with the RSAS (r=0.565, p<0.001). RSS was highly correlated with
the RASS (r=-0.664, p<0.001). CONCLUSIONS: Ramsay is both reliable and valid
(high correlation with the RASS and RSAS scales) in assessing agitation and
sedation in adult ICU patients.
PMID- 28412049
TI - More Than a Destination: Contraceptive Decision Making as a Journey.
AB - BACKGROUND: Contraceptive use is widely recognized as a means of reducing adverse
health-related outcomes. However, dominant paradigms of contraceptive counseling
may rely on a narrow definition of "evidence" (i.e., scientifically accurate but
exclusive of individual women's experiences). Given increased enthusiasm for long
acting, reversible contraceptive methods, such paradigms may reinforce counseling
that overprivileges effectiveness, particularly for groups considered at high
risk of unintended pregnancy. This study investigates where and how women's
experiences fit into the definition of evidence these counseling protocols use.
METHODS: Using a qualitative approach, this analysis draws on semistructured
interviews with 38 young (ages 18-24) Black and Latina women. We use a
qualitative content analysis approach, with coding categories derived directly
from the textual data. FINDINGS: Our analysis suggests that contraceptive
decision making is an iterative, relational, reflective journey. Throughout
contraceptive histories, participants described experiences evolving to create a
foundation from which decision-making power was drawn. The same contraceptive
related decisions were revisited repeatedly, with knowledge accrued along the
way. The cumulative experience of using, assigning meanings to, and developing
values around contraception meant that young women experienced contraceptive
decision making as a dynamic process. IMPLICATIONS FOR PRACTICE: This journey
creates a rich body of evidence that informs contraceptive decision making. To
provide appropriate, acceptable, patient-centered family planning care, providers
must engage with evidence grounded in women's expertise on their contraceptive
use in addition to medically accurate data on method effectiveness, side effects,
and contraindications.
PMID- 28412051
TI - [Impact of postoperative cognitive decline in quality of life: a prospective
study].
AB - BACKGROUND: Regardless the progress in perioperative care postoperative cognitive
decline (PCD) has been accepted unequivocally as a significant and frequent
complication of surgery in older patients. The aim of this study was to evaluate
the incidence of postoperative cognitive decline and its influence on quality of
life three months after surgery. METHODS: Observational, prospective study in a
Post-Anesthesia Care Unit (PACU) in patients aged above 45 years, after elective
major surgery. Cognitive function was assessed with Montreal Cognitive Assessment
(MOCA); Quality of life (QoL) was assessed using SF-36 Health Survey (SF-36).
Assessments were performed preoperatively (T0) and 3 months after surgery (T3).
RESULTS: Forty-one patients were studied. The incidence of PCD 3 months after
surgery was 24%. At T3 MOCA scores were lower in patients with PCD (median 20 vs.
25, p=0.009). When comparing the median scores for each of SF-36 domains, there
were no differences between patients with and without PCD. In patients with PCD,
and comparing each of SF-36 domains obtained before and three months after
surgery, had similar scores for every of the 8 SF-36 areas while patients without
PCD had better scores for six domains. At T3 patients with PCD presented with
higher levels of dependency in personal activities of daily living (ADL).
CONCLUSION: Three months after surgery patients without PCD had significant
improvement in MOCA scores. Patients with PCD obtained no increase in SF-36
scores but patients without PCD improved in almost all SF-36 domains. Patients
with PCD presented higher rates of dependency in personal ADL after surgery.
PMID- 28412052
TI - [The relationship between preoperative anxiety levels and vasovagal incidents
during the administration of spinal anesthesia].
AB - BACKGROUND: It was aimed to investigate the relationship between preoperative
anxiety and vasovagal symptoms observed during the administration of spinal
anesthesia in patients undergoing surgery in the perianal and inguinal regions.
METHODS: The study included patients with planned surgery for inguinal hernia
repair, anal fissure, hemorrhoid and pilonidal sinus excision. The study included
a total of 210 patients of ASA I-II, aged 18-65 years. Patients were evaluated in
respect of demographic characteristics, smoking and alcohol consumption, ASA
grade and educational level. Correlations were evaluated between the number of
attempts at spinal anesthesia and anesthesia history with vasovagal symptoms and
educational level, gender, smoking and alcohol consumption and anesthesia history
with anxiety scores. The instant (transient) state anxiety inventory part of the
Transient State/Trait Anxiety Inventory (State Trait Anxiety Inventory - STAI)
was used to determine the anxiety levels of the participants. Clinical findings
of peripheral vasodilation, hypotension, bradycardia and asystole observed during
the administration of spinal anesthesia were recorded. RESULTS: Vasovagal
incidences during the administration of spinal anesthesia were seen to increase
in cases of high anxiety score, male gender, and an absence of anesthesia
history. Educational level and the number of spinal needle punctures were not
found to have any effect on vasovagal incidents. CONCLUSION: The determination of
causes triggering vasovagal incidents seen during the application of spinal
anesthesia, better patient information of regional anesthesia implementations and
anxiety relief with preoperative anxiolytic treatment will help to eliminate
potential vasovagal incidents.
PMID- 28412053
TI - [The prognostic value of cerebral oxygen saturation measurement for assessing
prognosis after cardiopulmonary resuscitation].
AB - BACKGROUND: Despite new improvements on cardiopulmonary resuscitation (CPR),
brain damage is very often after resuscitation. OBJECTIVE: To assess the
prognostic value of cerebral oxygen saturation measurement (rSO2) for assessing
prognosis on patients after cardiopulmonary resuscitation. DESIGN: Retrospective
analysis. MEASUREMENTS AND RESULTS: We analyzed 25 post-CPR patients (12 female
and 13 male). All the patients were cooled to a target temperature of 33-34
degrees C. The Glascow Coma Scale (GCS), Corneal Reflexes (CR), Pupillary
Reflexes (PR), arterial Base Excess (BE) and rSO2 measurements were taken on
admission. The rewarming GCS, CR, PR, BE and rSO2 measurements were made after
the patient's temperature reached 36 degrees C. RESULTS: In survivors, the
baseline rSO2 value was 67.5 (46-70) and the percent difference between baseline
and rewarming rSO2 value was 0.03 (0.014-0.435). In non-survivors, the baseline
rSO2 value was 30 (25-65) and the percent difference between baseline and
rewarming rSO2 value was 0.031 (-0.08 to -20). No statistical difference was
detected on percent changes between baseline and rewarming values of rSO2.
Statistically significant difference was detected between baseline and rewarming
GCS groups (p=0.004). No statistical difference was detected between GCS, CR, PR,
BE and rSO2 to determine the prognosis. CONCLUSION: Despite higher values of rSO2
on survivors than non-survivors, we found no statistically considerable
difference between groups on baseline and the rewarming rSO2 values. Since the
measurement is simple, and not affected by hypotension and hypothermia, the rSO2
may be a useful predictor for determining the prognosis after CPR.
PMID- 28412054
TI - Community pharmacy transition of care services and rural hospital readmissions: A
case study.
AB - OBJECTIVES: To explore community pharmacist involvement in the transition of care
(TOC) process for patients discharged with acute myocardial infarction (AMI),
heart failure (HF), pneumonia, chronic obstructive pulmonary disease (COPD), or
elective total hip or knee arthroplasty (THA/TKA). SETTING: Patients discharged
from a 60-bed acute care hospital located in rural Missouri were seen by a
community pharmacist in 2 independent community pharmacy locations. PRACTICE
INNOVATION: Patients admitted with 1 of the 5 qualifying conditions and
identifying the participating pharmacy as their primary pharmacy spoke with a
community pharmacist within 72 hours of discharge to complete a comprehensive
medication review. A follow-up telephone call occurred 7 days after the encounter
to evaluate for drug-related problems, adherence, and key information recalled
from the previous visit. A final telephone call occurred on the 30th day after
discharge to assess for hospital readmissions and emergency department (ED)
visits. EVALUATION: Number of patients readmitted or visiting the ED within 30
days after discharge. RESULTS: Of the 9 patients completing the study, none were
readmitted or visited the ED within 30 days after discharge. All of the
participants were satisfied with the care and education provided by pharmacists.
The majority of patients recalled points related to specific medication education
topics. Based on the adherence tool, 8 of the 9 study participants had at least 1
barrier to medication access or adherence that could lead to post-discharge
medication-related problems. CONCLUSION: Community pharmacist involvement in the
TOC process may help to prevent readmissions for patients with AMI, HF,
pneumonia, COPD, and elective THA/TKA. Patients are overall satisfied with
community pharmacist involvement as they move from inpatient care to home. In
addition, there are multiple barriers affecting access and adherence to
medication therapy while at home, providing opportunities for pharmacist
intervention and assistance.
PMID- 28412055
TI - Impact of an open enrollment service on costs for Medicare Part D beneficiaries.
AB - OBJECTIVE: The primary objective was to determine total estimated cost savings
based on a patient's current medication regimen after comparing available
Medicare Part D plans for the upcoming year by using a plan comparison platform.
The secondary objective was to determine patient-centered concerns when
considering a change in Part D plans. DESIGN: Review of an open enrollment
service that included a patient survey and a Part D plan comparison. SETTING:
This study took place at a single independent community pharmacy in northwest
Alabama. PARTICIPANTS: Fifty-four patients eligible for Medicare Part D were
included in this study. MAIN OUTCOME MEASURES: The study was a review of an open
enrollment service that aids Medicare beneficiaries in selecting a Part D plan
that best fits their needs. It included a patient survey and plan comparison
using a plan comparison platform, during the 2015 Medicare open enrollment period
(October 15 to December 7). The survey assessed patient demographics, pharmacy
preferences, and cost concerns. Survey data were used to aid in plan selection
and analysis to determine the most common patient-centered concerns when
considering a change in plans. RESULTS: During the open enrollment period, 54
patients compared Medicare Part D plans. The majority of participants were female
(57%) and ranged in age from 65-69 years (37%) to 70-74 years (25.9%). The
majority of patients reported a preference for independent pharmacies (92.6%).
Deductible (40.7%) was the biggest concern for patients when comparing the main
cost variables for medication insurance. The average total cost difference per
patient per year showed that each patient saved an average of $1166.46.
CONCLUSION: The analysis of an independent pharmacy's open enrollment service
determined that a plan comparison platform is a valuable tool in helping patients
to compare and select cost-effective Medicare Part D prescription plans and in
helping patients save money.
PMID- 28412056
TI - Biomolecules from olive pruning waste in Sierra Magina - Engaging the energy
transition by multi-actor and multidisciplinary analyses.
AB - The price volatility of fossil resources, the uncertainty of their long-term
availability and the environmental, climatic and societal problems posed by their
operation lead to the need of an energy transition enabling the development and
utilization of other alternative and sustainable resources. Acknowledging that
indirect land-use change can increase greenhouse gas emission, the European Union
(EU) has reshaped its biofuel policy. It has set criteria for sustainability to
ensure that the use of biofuels guarantees real carbon savings and protects
biodiversity. From a sustainability perspective, biofuels and bioliquids offer
indeed both advantages (e.g., more secure energy supply, emission reductions,
reduced air pollution and production of high added-value molecules) as well as
risks (monocultures, reduced biodiversity and even higher emissions through land
use change). Approaching economic, environmental and social sustainability at the
local level and in an integrated way should help to maximize benefits and
minimize risks. This approach has been adopted and is described in the present
work that combines chemical, biological, social and territorial studies on the
management of pruning waste residues from olive trees in the Sierra Magina in
Spain. The biological and social analyses helped to orientate the research
towards an attractive chemical process based on extraction and pyrolysis, in
which high added value molecules are recovered and in which the residual biochar
may be used as pathogen-free fertilizer. In this region where farmers face
declining economic margins, the new intended method may both solve greenhouse gas
emission problems and provide farmers with additional revenues and convenient
fertilizers. Further research with a larger partnership will consolidate the
results and tackle issues such as the logistics.
PMID- 28412057
TI - Chemical characterization of biochar and assessment of the nutrient dynamics by
means of preliminary plant growth tests.
AB - Biochar can be produced from several organic sources with varying nutrients and
metal concentrations. Four commercial grade biochars were evaluated as peat
substitute. Biochars were characterised for plant nutrients and for biological
stability. The results showed that there were negligible quantities of N and P
and generally high levels of K and high biological stability. When these
materials were mixed with peat at 10, 25 and 50% and nutrients were added to
bring them to the same level of nutrients as in fertilized peat, it was found
that biochar mixtures considerably reduced the levels of calcium chloride/DTPA
(CAT) extractable N (including nitrate), P, and electrical conductivity- greater
extent with higher rates of biochar addition except for K. The pH and K levels
were increased with biochar addition. The drop in EC has important implications
regarding the use of other materials used to dilute peat, for example, composted
green waste, the rate of dilution is limited due to high EC and biochar addition
gives the potential for higher peat dilution of these materials. Nitrate and
phosphorus are very vulnerable to leaching of these nutrients in the environment
in peat substrates and the binding of these by biochar has implication for
leaching and nutrient application strategy. Root development using Cress test and
tomato plant height and biomass using containers, were in some cases better than
peat indicating that biochar could be used to dilute peat e.g. for seedling
production where root development and rapid growth are very important.
Application of biochars resulted in a marked reduction of N (and P) in the plant.
There were significant correlation between CAT extractable N and P and
corresponding plant concentration, indicating the standard growing media test,
CAT, would be suitable for assessing the nutrient status of peat biochar mixes.
PMID- 28412058
TI - Functional Outcomes and Cam Recurrence After Arthroscopic Treatment of
Femoroacetabular Impingement in Adolescents.
AB - PURPOSE: To compare the functional outcomes after arthroscopic treatment of
femoroacetabular impingement (FAI) in adolescent patients and non-adolescent
patients, and to report on the rate of cam recurrence within 2 years after
femoral osteoplasty in a limited sample of the adolescent group. METHODS: From
2010 to 2014, patients younger than 18 years with symptomatic FAI (alpha angle
>50 degrees ) who underwent hip arthroscopy with minimum 2-year follow-up or
reoperation were identified. A group of non-adolescent patients with identical
inclusion criteria, except age of 18 years or older, was also identified for
comparison. In addition, a separate group of adolescent patients with 2-year
postoperative radiographs was reviewed for cam recurrence. Demographic data,
operative data, and radiographic and clinical outcomes (modified Harris Hip Score
[mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score
Sport-Specific Subscale [HOS-SSS], and International Hip Outcome Tool 33 [iHOT
33] score) were collected. RESULTS: We identified 34 adolescent patients (38
hips) with an average age of 16 years (range, 13-17 years). The mean clinical
follow-up period was 36.1 +/- 11.6 months (range, 24.1-71.7 months) and 29.6 +/-
2.4 months (range, 27.9-31.3 months) without and with reoperation, respectively.
A control group of 296 non-adolescent patients (306 hips), with a mean age of 31
years (range, 18-59 years), was identified as our non-adolescent group. The mean
clinical follow-up period was 34.1 +/- 11 months (range, 24.0-77.4 months) and
15.1 +/- 9.1 months (range, 3.6-34.6 months) without and with reoperation,
respectively. Significant improvement was noted in adolescents in the changes in
outcome scores (mHHS, 22.2 [95% confidence interval (CI), 15.4-29.0]; HOS-ADL,
18.6 [95% CI, 11.9-25.2]; HOS-SSS, 33.5 [95% CI, 24.5-42.5]; and iHOT-33 score,
30.5 [95% CI, 21.8-39.2]; P < .001). Similar improvements were observed in non
adolescents (mHHS, 21.0 [95% CI, 19.0-23.0]; HOS-ADL, 16.6 [95% CI, 14.6-18.6];
HOS-SSS, 30.1 [95% CI, 26.6-33.6]; and iHOT-33 score, 34.9 [95% CI, 31.5-38.3]; P
< .001). There was no evidence of a difference in follow-up survey scores between
groups (P > .203). Revision surgery was required in 2 adolescent hips (5.3% [95%
CI, 1.5%-17.3%]) and 19 non-adolescent hips (6.2% [95% CI, 4.0%-9.5%]). Minimum 2
year radiographs were available for review in 24 adolescent patients (30 hips).
The alpha angle (mean +/- standard deviation) was reduced from 55.4 degrees +/-
12.1 degrees preoperatively to 38.7 degrees +/- 4.9 degrees at 6 weeks
postoperatively (mean difference, -16.4 degrees [95% CI, -19.8 degrees to -12.9
degrees ]; P < .001). At 2 years, the alpha angle remained at 39.2 degrees +/-
11.2 degrees , which did not differ from 6-week measurements (mean difference,
0.5 degrees [95% CI, -2.9 degrees to 3.9 degrees ]; P = .784). There were no
cases of cam recurrence (0% [95% CI, 0%-11.4%]). CONCLUSIONS: Significant
improvement in clinical outcomes can be anticipated after arthroscopic treatment
of FAI in adolescents. From a limited sample of our adolescent population, the
risk of cam recurrence appears low; however, further follow-up is needed to
ensure this does not represent a biased sample of the initial population. LEVEL
OF EVIDENCE: Level III, retrospective comparative study.
PMID- 28412059
TI - A Systematic Review of Tennis Elbow Surgery: Open Versus Arthroscopic Versus
Percutaneous Release of the Common Extensor Origin.
AB - PURPOSE: To compare complications, function, pain, and patient satisfaction after
conventional open, percutaneous, or arthroscopic release of the extensor origin
for the treatment of lateral epicondylitis. METHODS: A thorough review of 4
databases-PubMed, EBSCOhost, CINAHL (Cumulative Index to Nursing and Allied
Health Literature) Plus, and Scopus-was performed to identify all studies that
addressed surgical management of lateral epicondylitis. We included (1) studies
published between 2000 and 2015 and (2) studies with clearly defined surgical
techniques. We excluded (1) non-English-language manuscripts, (2) isolated case
reports, (3) studies with fewer than 10 subjects, (4) animal studies, (5) studies
with additional adjunctive procedures aside from release of the extensor origin,
(6) clinical or systematic review manuscripts, (7) studies with a follow-up
period of 6 months or less, and (8) studies in which less than 80% of patients
completed follow-up. Each study was analyzed for complication rates, functional
outcomes, pain, and patient satisfaction. RESULTS: Thirty reports were identified
that included 848 open, 578 arthroscopic, and 178 percutaneous releases. Patients
within each release group had a similar age (46 years vs 46 years vs 48 years; P
= .9 and P = .4, respectively), whereas there was a longer follow-up time in
patients who underwent surgery by an open technique (49.4 months vs 42.6 months
vs 23 months, P < .001). There were no differences in complication rates among
these techniques (3.8% vs 2.9% vs 3.9%; P = .5 and P = .9, respectively).
However, open techniques were correlated with higher surgical-site infection
rates than arthroscopic techniques (0.7% vs 0%, P = .04). Mean Disabilities of
the Arm, Shoulder and Hand scores were substantially better with both open and
arthroscopic techniques than with percutaneous release (19.9 points vs 21.3
points vs 29 points, P < .001). In addition, there was less pain reported in the
arthroscopic and percutaneous release groups as opposed to their open
counterparts (1.9 points vs 1.4 points vs 1.3 points, P < .0001). There were no
differences among the techniques in patient satisfaction rate (93.7% vs 89% vs
88%; P = .08 and P = .07, respectively). CONCLUSIONS: Functional outcomes of open
and arthroscopic releases may be superior to those of percutaneous release. In
addition, patients may report less pain with arthroscopic and percutaneous
techniques. Although the risk of complications is similar regardless of
technique, patients may be counseled that their risk of infectious complications
may be slightly higher with open releases. However, it is important to note that
this statistical difference may not necessarily portend noticeable clinical
differences. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV
evidence.
PMID- 28412060
TI - Minimum 2-Year Outcomes of Arthroscopic Management of Symptomatic Hip Labrum
Tears in Patients With Global Acetabular Overcoverage.
AB - PURPOSE: To report minimum 2-year patient-reported outcomes (PROs) after hip
arthroscopy (HA) for symptomatic labral tears in patients with global acetabular
overcoverage. METHODS: This study was a retrospective case series of patients who
underwent HA from April 2008 to April 2013. The inclusion criteria were patients
with global acetabular overcoverage, defined as a lateral center-edge angle
greater than 40 degrees , and with coxa profunda, defined radiologically by the
ilioischial line lateral to the acetabular floor. Only patients with minimum 2
year follow-up and no history of hip conditions or surgery were included. We
recorded demographic, examination, radiologic, and intraoperative findings;
intraoperative procedures performed; and the following PROs: modified Harris Hip
Score (mHHS), Non-Arthritic Hip Score, Hip Outcome Score-Activities of Daily
Living (HOS-ADL), Hip Outcome Score-Sports-Specific Subscale (HOS-SSS), visual
analog scale, and patient satisfaction. RESULTS: The inclusion criteria were met
by 39 patients, of whom 35 (89.7%) had 2-year follow-up. There was no distinct
pattern of examination findings. The study population had a mean acetabular
inclination of -1.19 degrees and an anterior center-edge angle of 35 degrees .
There was no association with measures of acetabular retroversion. Intrasubstance
tearing of the labrum occurred in 75% of patients (mean tear size, 2.68 hours on
acetabular clock face; mean location, 11.5 to 3 on acetabular clock face). There
were significant improvements in the mean scores for all PROs: mHHS, 13.5 +/-
17.7 points (P < .01); Non-Arthritic Hip Score, 14.3 +/- 21.3 (P < .001); HOS
ADL, 11.6 +/- 19.7 (P < .001); HOS-SSS, 17.1 +/- 35.1 (P < .001); and visual
analog scale, -2.77 +/- 2.58 (P < .001). The mean patient satisfaction rating was
6.61. The improvements in mHHS, HOS-ADL, and HOS-SSS did not reach the minimal
clinically important difference. The incidence of secondary procedures was 17% (4
patients underwent conversion to total hip arthroplasty and 2 required revision
HA). CONCLUSIONS: HA in patients with global acetabular overcoverage was
associated with improvements in PROs and pain at minimum 2-year follow-up.
However, these improvements did not reach the minimal clinically important
difference for the mHHS, HOS-ADL, and HOS-SSS. The incidence of secondary
procedures was 17%. The pattern of labral injury is predominantly intrasubstance
labral damage with a narrow rim of adjacent chondral injury. LEVEL OF EVIDENCE:
Level IV, therapeutic case series.
PMID- 28412061
TI - Influence of the Labrum on Version and Diameter of the Glenoid: A Morphometric
Study Using Magnetic Resonance Images.
AB - PURPOSE: To use magnetic resonance imaging to determine the influence of the
labrum on both the osseous version and effective diameter of the glenoid.
METHODS: This was a retrospective, cross-sectional study of patients with
shoulder pain who underwent MRI between February 2014 and February 2015. The
morphology of the glenoid labrum and glenoid was scanned with a 3-T magnetic
resonance imaging scanner, and variables were measured by use of IntelliSpace
PACS Enterprise. Patients were included if they were aged between 18 and 40 years
and the radiologist reported a normal glenohumeral joint or if they were young
patients aged less than 30 years with acute traumatic isolated partial- or full
thickness tears of the rotator cuff with a history of symptoms of less than 3
months. A pilot study was conducted with 3 observers and 3 repeated measurements
at intervals to determine the interobserver and intraobserver reliability. Data
analysis included descriptive statistics of measured variables, as well as paired
Student t tests to determine the relative difference between labral and osseous
morphometric variables. RESULTS: Excellent inter-rater reliability (0.95-0.96)
and intrarater reliability (0.93-0.98) were obtained in the pilot study of 20
patients. The study population was composed of 100 patients with a mean age of
37.3 years (standard deviation [SD], 11.8 years), having a gender distribution of
56 male and 44 female patients; there were 53 right and 47 left shoulders. The
glenoid osseous version measured -5.7 degrees (SD, 5.3 degrees ), and the labral
version measured -10 degrees (SD, 5.5 degrees ); the glenoid osseous diameter
measured 28.0 mm (SD, 3.3 mm), and the labral diameter measured 31.9 mm (SD, 3.2
mm). The labrum significantly increased the version by 4.3 degrees (P = .001)
and significantly increased the diameter by 3.9 mm (P = .001). CONCLUSIONS: The
results of this study showed that the labrum increased the effective glenoid
version by 75% (4.3 degrees of retroversion) and the effective glenoid diameter
by 14% (3.9 mm). LEVEL OF EVIDENCE: Level IV, prognostic case series.
PMID- 28412062
TI - Development and Internal Validation of a Novel Model to Identify the Candidates
for Extended Pelvic Lymph Node Dissection in Prostate Cancer.
AB - BACKGROUND: Preoperative assessment of the risk of lymph node invasion (LNI) is
mandatory to identify prostate cancer (PCa) patients who should receive an
extended pelvic lymph node dissection (ePLND). OBJECTIVE: To update a nomogram
predicting LNI in contemporary PCa patients with detailed biopsy reports. DESIGN,
SETTING, AND PARTICIPANTS: Overall, 681 patients with detailed biopsy
information, evaluated by a high-volume uropathologist, treated with radical
prostatectomy and ePLND between 2011 and 2016 were identified. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariable logistic regression model
predicting LNI was fitted and represented the basis for a coefficient-based
nomogram. The model was evaluated using the receiver operating characteristic
derived area under the curve (AUC), calibration plot, and decision-curve analyses
(DCAs). RESULTS AND LIMITATIONS: The median number of nodes removed was 16.
Overall, 79 (12%) patients had LNI. A multivariable model that included prostate
specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores
with highest-grade PCa, and percentage of cores with lower-grade disease
represented the basis for the nomogram. After cross validation, the predictive
accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated
improved risk prediction against threshold probabilities of LNI <=20%. Using a
cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven
(1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering
Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs
89.5%), better calibration characteristics, and a higher net benefit at DCA.
CONCLUSIONS: An ePLND should be avoided in patients with detailed biopsy
information and a risk of nodal involvement below 7%, in order to spare
approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. PATIENT SUMMARY:
We developed a novel nomogram to predict lymph node invasion (LNI) in patients
with clinically localized prostate cancer based on detailed biopsy reports. A
lymph node dissection exclusively in men with a risk of LNI >7% according to this
model would significantly reduce the number of unnecessary pelvic nodal
dissections with a risk of missing only 1.5% of patients with LNI.
PMID- 28412063
TI - Diagnostic Performance of Magnetic Resonance Imaging for the Detection of Bone
Metastasis in Prostate Cancer: A Systematic Review and Meta-analysis.
AB - CONTEXT: Magnetic resonance imaging (MRI) has been tested for detecting bone
metastasis and has shown promising results. Yet, consensus has not been reached
regarding whether it can replace the role of bone scintigraphy in this clinical
setting or not. OBJECTIVE: To review the diagnostic performance of contemporary
(>=1.5 T) MRI for the detection of bone metastasis in patients with prostate
cancer. EVIDENCE ACQUISITION: MEDLINE and EMBASE were searched up to January 22,
2017. We included studies that used MRI using >=1.5-T scanners for the detection
of bone metastasis in patients with prostate cancer, using histopathology or best
value comparator as the reference standard. Two independent reviewers assessed
the methodological quality using the Quality Assessment of Diagnostic Accuracy
Studies-2 tool. Per-patient sensitivity and specificity of included studies were
calculated, and pooled and plotted in a hierarchical summary receiver operating
characteristic plot. Meta-regression and sensitivity analyses were performed.
EVIDENCE SYNTHESIS: Ten studies (1031 patients) were included. Pooled sensitivity
was 0.96 (95% confidence interval [CI] 0.87-0.99) with a specificity of 0.98 (95%
CI 0.93-0.99). At meta-regression analysis, only the number of imaging planes
(>=2 vs 1) was a significant factor affecting heterogeneity (p<0.01). Sensitivity
analyses showed that specificity estimates were comparable and consistently high
across all subgroups, but sensitivity estimates demonstrated some differences.
Studies using two or more planes (n=4) had the highest sensitivity (0.99 [95% CI
0.98-1.00]). CONCLUSIONS: Contemporary MRI shows excellent sensitivity and
specificity for detection of bone metastasis in patients with prostate cancer.
Using two or more imaging planes may further improve sensitivity. However,
caution is needed in applying our results due to the heterogeneity among the
included studies. PATIENT SUMMARY: We reviewed studies using contemporary
magnetic resonance imaging (MRI) for the detection of bone metastasis in prostate
cancer patients. MRI shows excellent diagnostic performance in finding patients
with bone metastasis.
PMID- 28412064
TI - Re: Diagnostic Accuracy of Multi-parametric Magnetic Resonance Imaging and
Transrectal Ultrasound Biopsy in Prostate Cancer (PROMIS): A Paired Validating
Confirmatory Study.
PMID- 28412065
TI - Comparative Effectiveness of Trimodal Therapy Versus Radical Cystectomy for
Localized Muscle-invasive Urothelial Carcinoma of the Bladder.
AB - : Given the lack of randomized evidence comparing trimodal therapy (TMT) to
radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder
(UCB), we performed an observational cohort study to examine the comparative
effectiveness of these two definitive treatments. Within the National Cancer Data
Base (2004-2011),we identified 1257 (9.8%) and 11 586 (90.2%) patients who
received TMT and RC, respectively. Inverse probability of treatment weighting
(IPTW)-adjusted Kaplan-Meier analysis showed that median overall survival (OS)
was similar between the TMT (40 mo, 95% confidence interval [CI] 34-46) and RC
groups (43 mo 95% CI 41-45; p=0.3). In IPTW-adjusted Cox regression analysis with
a time-varying covariate, TMT was associated with a significant adverse impact on
long-term OS (hazard ratio 1.37, 95% CI 1.16-1.59; p<0.001). Interaction terms
indicated that the adverse treatment effect of TMT versus RC decreased with age
(p=0.004), while there was no significant interaction with gender (p=0.6),
Charlson comorbidity index (p=0.09) or cT stage (p=0.8). In conclusion, we found
that TMT was generally associated with worse long-term OS compared to RC for
muscle-invasive UCB. However, the survival benefit of RC should be weighed
against the risks of surgery, especially in older patients. These results are
preliminary and emphasize the need for a randomized controlled trial to compare
TMT versus RC. PATIENT SUMMARY: We examined the comparative effectiveness of
trimodal therapy versus radical cystectomy for muscle-invasive urothelial
carcinoma of the bladder. We found that trimodal therapy was generally associated
with worse long-term overall survival, although there may be no difference with
radical cystectomy in older individuals.
PMID- 28412066
TI - Ranibizumab Injection as Primary Treatment in Patients with Retinopathy of
Prematurity: Anatomic Outcomes and Influencing Factors.
AB - PURPOSE: To investigate the anatomic outcomes and influencing factors of
ranibizumab in the treatment of retinopathy of prematurity (ROP). DESIGN:
Retrospective case series. PARTICIPANTS: A total of 283 eyes of 145 patients with
type 1 ROP treated with intravitreal injection of ranibizumab (IVR) as primary
treatment. METHODS: Retrospective review of infants who were diagnosed with type
1 ROP and accepted IVR (0.25 mg/0.025 ml) as primary treatment from January 2012
to August 2015. The anatomic outcomes and the influencing factors were analyzed.
MAIN OUTCOME MEASURES: Anatomic outcomes of ROP eyes after IVR and the
influencing factors. RESULTS: A total of 283 eyes of 145 patients were included
in this study. There were a total of 266 eyes (94.0%) in the positive response
group and 17 eyes (6.0%) in the negative/no response group after IVR. Within the
positive response group, 139 eyes (48.6%) were in the regression without
reactivation subgroup, and 127 eyes (44.9%) were in the regression with
reactivation subgroup. A total of 152 eyes received additional laser or surgical
treatment. At the last visit, 278 eyes (98.2%) had attached retinas, and 5 eyes
(1.8%) had retinal detachment. A classification tree model showed that for
patients with gestational age (GA) <=29.5 weeks, the possibility of experiencing
reactivation after IVR is higher than that of those with GA >29.5 weeks (61.6%
vs. 29.6%). Moreover, for patients with GA <=29.5 weeks, those diagnosed with
zone II stage 2+ ROP have a lower possibility of experiencing reactivation than
other patients (37.9% vs. 80%). CONCLUSIONS: Intravitreal injection of
ranibizumab seemed to be effective in treating patients with ROP. After
treatment, there were primarily 3 different outcomes. Our predictive tree model
is helpful for ophthalmologists to evaluate the risk of reactivation.
PMID- 28412067
TI - Trend-based Analysis of Ganglion Cell-Inner Plexiform Layer Thickness Changes on
Optical Coherence Tomography in Glaucoma Progression.
AB - PURPOSE: To evaluate the rate of thinning in ganglion cell-inner plexiform layer
(GCIPL) thickness by optical coherence tomography (OCT) in glaucomatous eyes and
to use a trend-based approach to determine its diagnostic ability for detecting
glaucoma progression. DESIGN: Prospective, observational study. PARTICIPANTS:
Sixty-five patients with primary open-angle glaucoma with a minimum 3-year follow
up involving serial spectral-domain OCT measurement of GCIPL thickness. METHODS:
Patients were divided into a nonprogressor group (n = 38) and a progressor group
(n = 27) on the basis of serial red-free photography or visual field tests. The
rates of GCIPL thinning in the global region, affected hemifield, and 6 macular
sectors, and the minimum thickness, were determined by linear regression and
compared between groups. The area under the receiver operating characteristic
curves (AUCs) were calculated for each parameter. The GCIPL thinning rates were
compared between affected hemifields and unaffected hemifields. MAIN OUTCOME
MEASURES: The macular GCIPL thinning rates in the progressor and nonprogressor
groups and the ability of the GCIPL thinning rate to diagnose glaucoma
progression. RESULTS: The GCIPL thinning rate was significantly faster in
progressors than in nonprogressors in the global area (P < 0.001); in the
affected hemifield (P = 0.001); in the temporal, vertical, and nasal sectors of
the affected hemifield (P = 0.017, 0.032, and 0.030, respectively); and in the
minimum GCIPL thickness (P < 0.001). In the temporal sectors, the GCIPL thinning
rates were significantly faster in the affected than in the unaffected hemifield
(P = 0.013). The best GCIPL parameters were the global (AUC = 0.791), minimum
(AUC = 0.755), inferior hemifield (AUC = 0.708), and affected hemifield (AUC =
0.702) thinning rates. The global circumpapillary retinal nerve fiber layer
thinning rate correlated significantly with the global and inferotemporal sector
GCIPL thinning rates (rho = 0.259 and 0.366, respectively). CONCLUSIONS: The
GCIPL thinning rate on OCT was significantly faster for patients with glaucoma
with progression than for those without progression. The GCIPL thinning rate of
the temporal sector was faster in the affected than in the unaffected hemifield,
suggesting that the glaucomatous damage may progress locally in a specific
sequence. Trend-based analysis of GCIPL thickness on OCT may be useful for
assessing glaucoma progression objectively and quantitatively.
PMID- 28412068
TI - Vitreous Amyloidosis: Ocular, Systemic, and Genetic Insights.
AB - PURPOSE: To report the unique clinical and surgical characteristics encountered
in eyes with vitreous amyloidosis. Systemic evaluation and visual outcome after
vitrectomy are discussed. A novel mutation in the transthyretin gene (TTR) in
Indian patients with familial amyloid polyneuropathy (FAP) is described. DESIGN:
Retrospective, observational study. PARTICIPANTS: Ten eyes of 5 patients from 2
pedigrees with a diagnosis of vitreous amyloidosis. METHODS: Detailed history,
pedigree charting, systemic and ocular examination of 10 eyes (5 patients from 2
pedigrees) were carried out. Tests were performed to rule out vitreitis, retinal
vasculitis, vitreous hemorrhage, and systemic amyloidosis. Genetic analysis to
identify the mutation was performed in 1 patient. Vitreous biopsy, followed by 25
gauge pars plana vitrectomy, was performed in the same sitting in all cases.
Samples were sent for Congo red staining and polarized microscopy. Patients were
followed up on days 1, 7, and 28 and then every 2 months. Visual acuity
assessment, intraocular pressure measurement, and fundus examination were
performed each time. MAIN OUTCOME MEASURES: Mutations in TTR and postoperative
visual acuity. RESULTS: Mean age at presentation was 32 years, with a 3:2 male-to
female distribution. Family history was positive in all patients. Nine eyes had
pseudopodia lentis, whereas all 10 had glass wool-like vitreous. Glaucoma
developed in 1 patient (2 eyes). Waxy paper-like vitreous with firm vitreous
adhesions beyond major arcades and along retinal vessels was noted during surgery
in all eyes. Congo red staining and apple green birefringence demonstrated
vitreous amyloidosis. The mean preoperative best-corrected visual acuity (BCVA)
was 1.39+/-0.64 logarithm of the minimum angle of resolution (logMAR), whereas
the postoperative BCVA improved to 0.17+/-0.07 logMAR (P = 0.004). Gene
sequencing revealed a phenylalanine->isoleucine mutation in the 33rd position of
exon 2 of TTR in 1 patient of 1 pedigree, confirming the diagnosis of FAP. Two
patients subsequently were found to have sensorimotor autonomic neuropathy,
whereas 2 others had subclinical autonomic dysfunction. CONCLUSIONS: The clinical
clues, management strategy, surgical characteristics, vitrectomy outcomes, and
significance of systemic evaluation in vitreous amyloidosis are highlighted. A
novel single mutation (Phe33Ile) in a case of FAP with vitreous amyloidosis from
India is reported.
PMID- 28412069
TI - Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of
Retinitis Pigmentosa Accompanied by Pseudocoloboma.
AB - PURPOSE: To identify the genetic cause of and describe the phenotype in 4
families with autosomal recessive retinitis pigmentosa (arRP) that can be
associated with pseudocoloboma. DESIGN: Case series. PARTICIPANTS: Seven patients
from 4 unrelated families with arRP, among whom 3 patients had bilateral early
onset macular pseudocoloboma. METHODS: We performed homozygosity mapping and
whole-exome sequencing in 5 probands and 2 unaffected family members from 4
unrelated families. Subsequently, Sanger sequencing and segregation analysis were
performed in additional family members. We reviewed the medical history of
individuals carrying IDH3A variants and performed additional ophthalmic
examinations, including full-field electroretinography, fundus photography,
fundus autofluorescence imaging, and optical coherence tomography. MAIN OUTCOME
MEASURES: IDH3A variants, age at diagnosis, visual acuity, fundus appearance,
visual field, and full-field electroretinography, fundus autofluorescence, and
optical coherence tomography findings. RESULTS: We identified 7 different
variants in IDH3A in 4 unrelated families, that is, 5 missense, 1 nonsense, and 1
frameshift variant. All participants showed symptoms early in life, ranging from
night blindness to decreased visual acuity, and were diagnosed between the ages
of 1 and 11 years. Four participants with biallelic IDH3A variants displayed a
typical arRP phenotype and 3 participants were diagnosed with arRP and
pseudocoloboma of the macula. CONCLUSIONS: IDH3A variants were identified as a
novel cause of typical arRP in some individuals associated with macular
pseudocoloboma. We observed both phenotypes in 2 siblings carrying the same
compound heterozygous variants, which could be explained by variable disease
expression and warrants caution when making assertions about genotype-phenotype
correlations.
PMID- 28412070
TI - Evaluation of Femtosecond Laser Intrastromal Incision Location Using Optical
Coherence Tomography.
AB - PURPOSE: To use optical coherence tomography (OCT) to evaluate the femtosecond
laser intrastromal incisions made during cataract surgery to reduce corneal
astigmatism. DESIGN: Retrospective case series. PARTICIPANTS: Seventy-seven eyes
of 77 patients. METHODS: Paired intrastromal incisions were created using the
Catalys femtosecond laser (Abbott Medical Optics, Inc., Santa Ana, CA). The
planned intrastromal incision parameters were 20% uncut anterior, 20% uncut
posterior, midpoint depth of 50%, and 90 degrees side cut angle. Optical
coherence tomography scans were obtained 3 weeks or more after surgery to assess
these 4 parameters, and actual values were compared with intended values. MAIN
OUTCOME MEASURES: Percentages of uncut anterior and posterior tissue, midpoint
depth, and degrees of side cut angle. RESULTS: The mean values were 17.2+/-5.8%
(range, 7.2%-36.9%) for uncut anterior, 32.5+/-8.8% (range, 6.0%-57.9%) for uncut
posterior, and 42.3+/-6.6% (range, 25.5%-65.4%) for midpoint depth, which all
were significantly different from the planned parameters (all P < 0.05). The mean
side cut angle was 88.5 degrees +/-5.6 degrees (range, 71 degrees -114 degrees )
and was significantly different from the planned side cut angle of 90 degrees (P
< 0.05). In 50 eyes that had paired intrastromal incisions scanned by the OCT,
there was no correlation between the paired incisions for midpoint depth and side
cut angle (correlation coefficient, r = -0.063 and -0.067, respectively; P >
0.05). CONCLUSIONS: The intrastromal incision midpoint depth was significantly
more anterior than the planned depth of 50%. The locations of paired intrastromal
incisions in each eye were not correlated. Further improvements are needed to
ensure the precise location of the intrastromal incisions made with this device.
PMID- 28412071
TI - Emergency Medicine Myths: Cerebral Edema in Pediatric Diabetic Ketoacidosis and
Intravenous Fluids.
AB - BACKGROUND: Pediatric diabetic ketoacidosis (DKA) is a disease associated with
several complications that can be severe. One complication includes cerebral
edema (CE), and patients may experience significant morbidity with this disease.
OBJECTIVE: This review evaluates the myths concerning CE in pediatric DKA
including mechanism, presentation of edema, clinical assessment of dehydration,
and association with intravenous (i.v.) fluids. DISCUSSION: Multiple
complications may occur in pediatric DKA. CE occurs in < 1% of pediatric DKA
cases, though morbidity and mortality are severe without treatment. Several myths
surround this disease. Subclinical CE is likely present in many patients with
pediatric DKA, though severe disease is rare. A multitude of mechanisms likely
account for development of CE, including vasogenic and cytotoxic causes. Clinical
dehydration is difficult to assess. Literature has evaluated the association of
fluid infusion with the development of CE, but most studies are retrospective,
with no comparator groups. The few studies with comparisons suggest fluid
infusion is not associated with DKA. Rather, the severity of DKA with higher
blood urea nitrogen and greater acidosis contribute to CE. Multiple strategies
for fluid replacement exist. A bolus of 10 mL/kg of i.v. fluid is likely safe,
which can be repeated if hemodynamic status does not improve. CONCLUSIONS:
Pediatric CE in DKA is rare but severe. Multiple mechanisms result in this
disease, and many patients experience subclinical CE. Intravenous fluids are
likely not associated with development of CE, and 10-mL/kg or 20-mL/kg i.v. bolus
is safe.
PMID- 28412072
TI - Do Slow and Steady Residents Win the Race? Modeling the Effects of Peak and
Overall Resident Productivity in the Emergency Department.
AB - BACKGROUND: Emergency medicine residents need to be staffed in a way that
balances operational needs with their educational experience. Key to developing
an optimal schedule is knowing a resident's expected productivity, a poorly
understood metric. OBJECTIVE: We sought to measure how a resident's busiest
(peak) workload affects their overall productivity for the shift. METHODS: We
conducted a retrospective, observational study of resident productivity at an
urban, tertiary care center with a 3-year Accreditation Council for Graduate
Medical Education-approved emergency medicine training program, with 55,000
visits annually. We abstracted resident productivity data from a database of
patient assignments from July 1, 2010 to June 20, 2015, utilizing a generalized
estimation equation method to evaluate physician shifts. Our primary outcome
measure was the total number of patients seen by a resident over a shift. The
secondary outcome was the number of patients seen excluding those in the peak
hour. RESULTS: A total of 14,361 shifts were evaluated. Multivariate analysis
showed that the total number of patients seen was significantly associated with
the number of patients seen during the peak hour, level of training, the timing
of the shift, but most prominently, lower variance in patients seen per hour
(coefficient of variation < 0.10). CONCLUSIONS: A resident's peak productivity
can be a strong predictor of their overall productivity, but the substantial
negative effect of variability favors a steadier pace. This suggests that
resident staffing and patient assignments should generally be oriented toward a
more consistent workload, an effect that should be further investigated with
attending physicians.
PMID- 28412073
TI - Pediatric Acute Flaccid Paralysis: Enterovirus D68-Associated Anterior Myelitis.
AB - BACKGROUND: Enteroviral infections can cause acute flaccid paralysis secondary to
anterior myelitis. Magnetic resonance imaging (MRI) is important in the diagnosis
of this potentially devastating pediatric disease. Before the 2014 outbreak of
Enterovirus D68 (EV-D68), the virus was considered a relatively benign disease.
CASE REPORT: A fully immunized 8-year-old boy was brought to the emergency
department complaining of a cough, headache, neck pain, and right arm pain and
weakness. Deep tendon reflexes in the weak arm could not be elicited. MRI of the
brain and cervical spine revealed anterior myelitis of the cervical spine. The
patient was given intravenous antibiotics, acyclovir, and methylprednisolone with
no initial improvement. He was then given intravenous immunoglobulin over 3 days
with improvement in symptoms. Nasal swab polymerase chain reaction revealed EV
D68. Despite medical management, the child was left with long-term motor
disability in the effected extremity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
OF THIS?: Acute flaccid paralysis is a potential devastating complication of
enteroviral infections. Extremity complaints in the clinical setting of central
nervous system infection should raise concern for encephalomyelitis. MRI is
extremely helpful in establishing this diagnosis. Prevalence of non-polio
enteroviral paralytic events is increasing in the United States. Potential EV-D68
cases should be reported to local health departments. Emergency medicine
providers should consider this complication in the child with acute, unexplained
significant respiratory illness with new neurologic complaints.
PMID- 28412074
TI - Reversible synthesis of colanic acid and O-antigen polysaccharides in Salmonella
Typhimurium enhances induction of cross-immune responses and provides protection
against heterologous Salmonella challenge.
AB - Colanic Acid (CA) and lipopolysaccharide (LPS) are two major mannose-containing
extracellular polysaccharides of Salmonella. Their presence on the bacterial
surface can mask conserved protective outer membrane proteins (OMPs) from the
host immune system. The mannose moiety in these molecules is derived from GDP
mannose, which is synthesized in several steps. The first two steps require the
action of phosphomannose isomerase, encoded by pmi (manA), followed by
phosphomannomutase, encoded by manB. There are two copies of manB present in the
Salmonella chromosome, one located in the cps gene cluster (cpsG) responsible for
CA synthesis, and the other in the rfb gene cluster (rfbK) involved in LPS O
antigen synthesis. In this study, it was demonstrated that the products of cpsG
and rfbK are isozymes. To evaluate the impact of these genes on O-antigen
synthesis, virulence and immunogenicity, single mutations (Deltapmi, DeltarfbK or
DeltacpsG) and a double mutation (DeltarfbK DeltacpsG) were introduced into both
wild-type Salmonella enterica and an attenuated Deltacya Deltacrp vaccine strain.
The Deltapmi, DeltarfbK and DeltacpsG DeltarfbK mutants were defective in LPS
synthesis and attenuated for virulence. In orally inoculated mice, strain S122
(Deltacrp Deltacya DeltacpsG DeltarfbK) and its parent S738 (Deltacrp Deltacya)
were both avirulent and colonized internal tissues. Strain S122 elicited higher
levels of anti-S. Typhimurium OMP serum IgG than its parent strain. Mice
immunized with S122 were completely protected against challenge with wild-type
virulent S. Typhimurium and partially protected against challenge with either
wild-type virulent S. Choleraesuis or S. Enteritidis. These data indicate that
deletions in rfbK and cpsG are useful mutations for inclusion in future
attenuated Salmonella vaccine strains to induce cross-protective immunity.
PMID- 28412075
TI - Vaccine preferences and acceptance of older adults.
AB - BACKGROUND: Expanding vaccination programs for the older population might be
important as older adults are becoming a larger proportion of the general
population. The aim of this study is to determine the relative importance of
vaccine and disease specific characteristics and acceptance for Dutch older
adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and
influenza vaccination. METHODS: A discrete choice experiment was conducted to
generate choice data that was analyzed using a mixed multinomial logit
statistical model. RESULTS: Important factors that were associated with
vaccination acceptance in older adults are high mortality risk of the infectious
disease, high susceptibility of getting the infectious disease, and high vaccine
effectiveness. Age, influenza vaccination in 2013 and self-perceived health score
were identified as personal factors that affect vaccine preference. Potential
vaccination rates of older adults were estimated at 68.1% for pneumococcal
vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination
and 54.3% for influenza vaccination. For persons aged 50-65, potential
vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for
herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for
influenza vaccination. For persons aged 65 and older, these were respectively
76.2%, 67.5%, 57.5% and 65.5%. DISCUSSION: Our results suggest that older adults
are most likely to accept pneumococcal vaccination of the four vaccines.
Information provision accompanied with the implementation of a new vaccine has to
be tailored for the individual and the vaccine it concerns. Special attention is
needed to ensure high uptake among persons aged 50-65years.
PMID- 28412076
TI - Varicella vaccination elicits a humoral and cellular response in children with
rheumatic diseases using immune suppressive treatment.
AB - OBJECTIVE: To assess humoral and cellular responses to live-attenuated varicella
zoster virus (VZV) vaccination of patients with juvenile idiopathic arthritis
(JIA), juvenile dermatomyositis (JDM) or juvenile scleroderma (JScle) compared to
those of healthy controls (HC). METHODS: Before, 4-6weeks and one year after VZV
vaccination, blood samples of patients and HC were collected. VZV-specific
antibody concentrations were measured by ELISA and multiplex immune-assay. IFN
gamma ELISpot assays were performed to assess VZV-specific T-cell responses.
Cytokine production upon VZV stimulation were measured with a Luminex-assay.
RESULTS: 49 patients (39 JIA, 5 JDM, 5 JScle) and 18 HC were included. All
patients used methotrexate (MTX), 16 also used corticosteroids, 3 patients used
biologics. No disease flares were reported after vaccination. Antibody response
to the vaccine was similar in patients and controls (p=0.139). Use of
immunosuppressive drugs did not affect the response (p=0.203). A second
vaccination (n=21) increased VZV-specific antibody concentrations (p=0.02). VZV
specific T-cells increased after vaccination (p=0.043), with a cytokine profile
suggesting a VZV-specific Th1 and cytotoxic T-cell response. CONCLUSION: The
humoral response to VZV vaccination in patients with pediatric rheumatic diseases
(PRD) is similar to that of HC. Generally, patients are able to mount a VZV
specific cellular response. This study has been registered in the Brazilian
Clinical Trials Registry under number U1111-1189-9837.
PMID- 28412077
TI - Influenza vaccine effectiveness estimates in the Dutch population from 2003 to
2014: The test-negative design case-control study with different control groups.
AB - Information about influenza vaccine effectiveness (IVE) is important for vaccine
strain selection and immunization policy decisions. The test-negative design
(TND) case-control study is commonly used to obtain IVE estimates. However, the
definition of the control patients may influence IVE estimates. We have conducted
a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database
which includes data from patients who consulted the General Practitioner (GP) for
an episode of acute influenza-like illness (ILI) or acute respiratory infection
(ARI) with known influenza vaccination status. Cases were patients tested
positive for influenza virus. Controls were grouped into those who tested (1)
negative for influenza virus (all influenza negative), (2) negative for influenza
virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus
(non-influenza virus positive), and (3) negative for these four viruses (pan
negative). We estimated the IVE over all epidemic seasons from 2003/2004 through
2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched
seasons and the individual seasons using generalized linear mixed-effect and
multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI
diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15-48), 64%
(95% CI: 49-75) and 21% (95% CI: -1 to 39) for all influenza negative, non
influenza virus positive and pan-negative controls, respectively. In both the
main and subgroup analyses IVE estimates were the highest using non-influenza
virus positive controls, likely due to limiting inclusion of controls without
laboratory-confirmation of a virus causing the respiratory disease.
PMID- 28412078
TI - A rare tumor of the auricle.
PMID- 28412079
TI - Polymyalgia rheumatica and vagal paraganglioma.
AB - INTRODUCTION: Vagal paraganglioma are rare tumors that are mostly asymptomatic.
We report a case of vagal paraganglioma associated with paraneoplastic
polymyalgia rheumatica and review the literature on benign paragangliomas of the
head and neck associated with paraneoplastic syndrome. CASE REPORT: A 53-year-old
man presented with atypical polymyalgia rheumatica. MRI revealed a tumor that was
then surgically excised. Histological examination confirmed the diagnosis of
benign vagal paraganglioma. Rapid, complete and permanent resolution of all
rheumatological symptoms were observed postoperatively, confirming the diagnosis
of paraneoplastic polymyalgia rheumatica. CONCLUSION: Paraganglioma of the neck
associated with paraneoplastic syndrome remains exceptional. A predisposing gene
mutation must be systematically investigated. Long-term surveillance must be
ensured due to the risk of local recurrence, second tumors or metastasis.
PMID- 28412080
TI - Reproductive parameters of critically endangered European mink (Mustela lutreola)
in captivity.
AB - Founding captive populations is often the last chance for saving endangered
species from extinction. Ensuring successful reproduction is typically most
critical for the maintenance of captive populations, with purposeful selection of
individuals for breeding being one of the crucial aspects. Comparable cross
species data on the determinants of reproduction success are most useful for
solving problems in captive species programs. In the present study, we provide an
overview of a 20-year captive breeding program of the critically endangered
European mink. The mating season starts in March, reaching its peak in the middle
of April. The average gestation length was 43.8days (mode 43), the mean litter
size being 4.4 (mode 4). Litter size and cub survival were negatively correlated
with maternal age but this effect was entirely due to the lower performance of
the females over 4 years of age. Female body weight also showed a positive
correlation with litter size, with the weight itself having increased by 10%
during the 20- year period. We did not find any signs of a cost of reproduction:
the number of litters the female had delivered earlier in her life did not have
an effect on her litter size in the focal year. Beyond the effect of age and
size, individual females did not differ in litter sizes. Consistently, we found
the heritability of litter size to be low. We conclude that, when selecting
females for breeding, there is little need to consider aspects other than genetic
relatedness crucial for avoiding progressive inbreeding.
PMID- 28412082
TI - Corrigendum to "The combination of UCP3-55CT and PPARgamma2Pro12Ala polymorphisms
affects BMI and substrate oxidation in two diabetic populations" [Nutr Metab
Cardiovasc Dis 26 (2016) 400-406].
PMID- 28412081
TI - Nasopharyngeal polymicrobial colonization during health, viral upper respiratory
infection and upper respiratory bacterial infection.
AB - OBJECTIVES: We sought to understand how polymicrobial colonization varies during
health, viral upper respiratory infection (URI) and acute upper respiratory
bacterial infection to understand differences in infection-prone vs. non-prone
patients. METHODS: Nasopharyngeal (NP) samples were collected from 74 acute
otitis media (AOM) infection-prone and 754 non-prone children during 2094 healthy
visits, 673 viral URI visits and 631 AOM visits. Three otopathogens Streptococcus
pneumoniae (Spn), Nontypeable Haemophilus influenzae (NTHi), and Moraxella
catarrhalis (Mcat) were identified by culture. RESULTS: NP colonization rates of
multiple otopathogens during health were significantly lower than during viral
URI, and during URI they were lower than at onset of upper respiratory bacterial
infection in both AOM infection-prone and non-prone children. AOM infection-prone
children had higher polymicrobial colonization rates than non-prone children
during health, viral URI and AOM. Polymicrobial colonization rates of AOM
infection-prone children during health were equivalent to that of non-prone
children during viral URI, and during viral URI were equivalent to that of non
prone during AOM infection. Spn colonization was positively associated with NTHi
and Mcat colonization during health, but negatively during AOM infection.
CONCLUSION: The infection-prone patients more frequently have multiple potential
bacterial pathogens in the NP than the non-prone patients. Polymicrobial
interaction in the NP differs during health and at onset of infection.
PMID- 28412083
TI - Elucidation of the complex metabolic profile of cerebrospinal fluid using an
untargeted biochemical profiling assay.
AB - We sought to determine the molecular composition of human cerebrospinal fluid
(CSF) and identify the biochemical pathways represented in CSF to understand the
potential for untargeted screening of inborn errors of metabolism (IEMs).
Biochemical profiles for each sample were obtained using an integrated
metabolomics workflow comprised of four chromatographic techniques followed by
mass spectrometry. Secondarily, we wanted to compare the biochemical profile of
CSF with those of plasma and urine within the integrated mass spectrometric-based
metabolomic workflow. Three sample types, CSF (N=30), urine (N=40) and EDTA
plasma (N=31), were analyzed from retrospectively collected pediatric cohorts of
equivalent age and gender characteristics. We identified 435 biochemicals in CSF
representing numerous biological and chemical/structural families. Sixty-three
percent (273 of 435) of the biochemicals detected in CSF also were detected in
urine and plasma, another 32% (140 of 435) were detected in either plasma or
urine, and 5% (22 of 435) were detected only in CSF. Analyses of several
metabolites showed agreement between clinically useful assays and the
metabolomics approach. An additional set of CSF and plasma samples collected from
the same patient revealed correlation between several biochemicals detected in
paired samples. Finally, analysis of CSF from a pediatric case with
dihydropteridine reductase (DHPR) deficiency demonstrated the utility of
untargeted global metabolic phenotyping as a broad assessment to screen samples
from patients with undifferentiated phenotypes. The results indicate a single CSF
sample processed with an integrated metabolomics workflow can be used to identify
a large breadth of biochemicals that could be useful for identifying disrupted
metabolic patterns associated with IEMs.
PMID- 28412084
TI - Coding update of the SMFM definition of low risk for cesarean delivery from ICD-9
CM to ICD-10-CM.
AB - In 2015, the Society for Maternal-Fetal Medicine developed a low risk for
cesarean delivery definition based on administrative claims-based diagnosis codes
described by the International Classification of Diseases, Ninth Revision,
Clinical Modification. The Society for Maternal-Fetal Medicine definition is a
clinical enrichment of 2 available measures from the Joint Commission and the
Agency for Healthcare Research and Quality measures. The Society for Maternal
Fetal Medicine measure excludes diagnosis codes that represent clinically
relevant risk factors that are absolute or relative contraindications to vaginal
birth while retaining diagnosis codes such as labor disorders that are
discretionary risk factors for cesarean delivery. The introduction of the
International Statistical Classification of Diseases, 10th Revision, Clinical
Modification in October 2015 expanded the number of available diagnosis codes and
enabled a greater depth and breadth of clinical description. These coding
improvements further enhance the clinical validity of the Society for Maternal
Fetal Medicine definition and its potential utility in tracking progress toward
the goal of safely lowering the US cesarean delivery rate. This report updates
the Society for Maternal-Fetal Medicine definition of low risk for cesarean
delivery using International Statistical Classification of Diseases, 10th
Revision, Clinical Modification coding.
PMID- 28412085
TI - In vivo evidence of significant levator ani muscle stretch on MR images of a live
childbirth.
AB - OBJECTIVE: Vaginal childbirth is believed to be a significant risk factor for the
development of pelvic floor dysfunction later in life. Previous studies have
explored the use of medical imaging and simulations of childbirth to determine
the stretch in the levator ani muscle. A report in 2012 has recorded magnetic
resonance images of a live childbirth of a 24 year old woman giving birth
vaginally for the second time, using a 1.0 Tesla open, high-field scanner. Our
objective was to determine the stretch ratios in the levator muscle using these
magnetic resonance images of live childbirth. STUDY DESIGN: Three-dimensional
magnetic resonance image sequences were obtained to visualize coronal and axial
planes before and after the childbirth. These images were obtained before the
expulsion phase without pushing and were used to reconstruct the levator muscle
and the fetal head in 3 dimensions. The fetal head was approximated to be an
ellipsoid, and it is assumed that its middle section is visible in dynamic
magnetic resonance images. Assuming incompressibility, the full deformation field
of the fetal head is then calculated. Real-time cine magnetic resonance images
were acquired for the during the expulsion phase, occurring over 2 contractions
in the midsagittal plane. The levator muscle stretch is estimated using a custom
program. The program calculates points of contact between the fetal head
ellipsoid and the levator ani muscle model as the head descends down the birth
canal and moves them orthogonal to its surface. Circumferential stretch was
calculated to represent the extension needed to allow the passage of the fetal
head. RESULTS: Starting from a position in the preexpulsion phase, the levator
muscle experiences a maximum circumferential stretch of 248% on the posterior
medial portion of the levator ani muscle, as shown in previously published finite
element simulations. However, the maximal stretch was notably less than that
predicted by finite element models. This is because our baseline 3-dimensional
model of the levator muscle is created from images taken shortly before expulsion
and thus is already in a stretched state. Furthermore, the finite element models
are created from images of a healthy nulliparous woman, while this study uses
images from a para 2 woman. CONCLUSION: This study is the first attempt to
estimate the stretch in levator ani muscle using magnetic resonance images of a
live childbirth. The stretch was significant and the locations corroborate with
previous findings of finite element models.
PMID- 28412086
TI - Tocolysis after preterm premature rupture of membranes and neonatal outcome: a
propensity-score analysis.
AB - BACKGROUND: There are conflicting results regarding tocolysis in cases of preterm
premature rupture of membranes. Delaying delivery may reduce neonatal morbidity
because of prematurity and allow for prenatal corticosteroids and, if necessary,
in utero transfer. However, that may increase the risks of maternofetal infection
and its adverse consequences. OBJECTIVE: The objective of the study was to
investigate whether tocolytic therapy in cases of preterm premature rupture of
membranes is associated with improved neonatal or obstetric outcomes. STUDY
DESIGN: Etude Epidemiologique sur les Petits Ages Gestationnels 2 is a French
national prospective, population-based cohort study of preterm births that
occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were
women with preterm premature rupture of membranes at 24-32 weeks' gestation and
singleton gestations. Outcomes were survival to discharge without severe
morbidity, latency prolonged by >=48 hours and histological chorioamnionitis.
Uterine contractions at admission, individual and obstetric characteristics, and
neonatal outcomes were compared by tocolytic treatment or not. Propensity scores
and inverse probability of treatment weighting for each woman were used to
minimize indication bias in estimating the association of tocolytic therapy with
outcomes. RESULTS: The study population consisted of 803 women; 596 (73.4%)
received tocolysis. Women with and without tocolysis did not differ in neonatal
survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by
>=48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs
47.6%, P = .73). After applying propensity scores and assigning inverse
probability of treatment weighting, tocolysis was not associated with improved
survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01
[95% confidence interval, 0.94-1.09], latency prolonged by >=48 hours (1.03 [95%
confidence interval, 0.95-1.11]), or histological chorioamnionitis (1.03 [95%
confidence interval, 0.92-1.17]). There was no association between the initial
tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs
no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm
premature rupture of membranes at 26-31 weeks' gestation, women who delivered at
least 12 hours after rupture of membranes, women with direct admission after the
rupture of membranes and the presence or absence of contractions gave similar
results. CONCLUSION: Tocolysis in cases of preterm premature rupture of membranes
is not associated with improved obstetric or neonatal outcomes; its clinical
benefit remains unproven.
PMID- 28412088
TI - Tobacco smoking and its association with cognition in first episode psychosis
patients.
AB - Available evidence suggests that nicotine may enhance cognitive functioning.
Moreover, it has been suggested that the high prevalence of smoking in people
with schizophrenia is in part due to self-medication behaviour to alleviate
cognitive deficits. We assessed the association between tobacco smoking and
cognitive functioning in a large population of first episode psychosis (FEP)
patients (n=304) and healthy controls (n=156). Smokers were not tobacco deprived,
or were minimally deprived (<=2h). Verbal memory, visual memory, working memory,
processing speed, executive function, motor dexterity and attention were
assessed. The smoking prevalence among the FEP group was 57% (n=174). The age at
which patients began smoking cigarettes regularly was 16.2years (SD=3.1), an
average of 12years before experiencing the first frank symptoms of psychosis (age
of onset=28.8; SD=9.3). The number of cigarettes smoked per day was 19.6
(SD=9.4), significantly more than healthy controls [11.0 (SD=7.6); p<0.001].
ANCOVA analysis did not show any significant difference between smokers and non
smokers in in the performance of any of the cognitive tasks in the FEP group or
in the healthy control group, independent of gender, age, education or premorbid
IQ. This suggests chronic exposure to nicotine through cigarette smoking is not
associated with cognitive functioning in first-episode psychosis. These findings
do not support the nicotine self-medication hypothesis as a contributor to the
high prevalence of smoking among individuals suffering from serious mental
illness.
PMID- 28412087
TI - Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine
embryo through cardiac remodeling and fibrosis.
AB - BACKGROUND: Cardiac hypertrophy is highly prevalent in patients with type 2
diabetes mellitus. Experimental evidence has implied that pregnant women with
type 2 diabetes mellitus and their children are at an increased risk of
cardiovascular diseases. Our previous mouse model study revealed that maternal
type 2 diabetes mellitus induces structural heart defects in their offspring.
OBJECTIVE: This study aims to determine whether maternal type 2 diabetes mellitus
induces embryonic heart hypertrophy in a murine model of diabetic embryopathy.
STUDY DESIGN: The type 2 diabetes mellitus embryopathy model was established by
feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks.
Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by
measuring heart size and thickness of the right and left ventricle walls and the
interventricular septum, as well as the expression of beta-myosin heavy chain,
atrial natriuretic peptide, insulin-like growth factor-1, desmin, and
adrenomedullin. Cardiac remodeling was determined by collagen synthesis and
fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining
the expression of connective tissue growth factor, osteopontin, and galectin-3
genes. Cell apoptosis also was measured in the developing heart. RESULTS: The
thicknesses of the left ventricle walls and the interventricular septum of
embryonic hearts exposed to maternal diabetes were significantly thicker than
those in the nondiabetic group. Maternal diabetes significantly increased beta
myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and
desmin expression, but decreased expression of adrenomedullin. Moreover, collagen
synthesis was significantly elevated, whereas fibronectin synthesis was
suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac
remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis
marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type
2 diabetes mellitus activated the proapoptotic c-Jun-N-terminal kinase 1/2 stress
signaling and triggered cell apoptosis by increasing the number of terminal
deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling
positive cells (10.4 +/- 2.2% of the type 2 diabetes mellitus group vs 3.8 +/-
0.7% of the nondiabetic group, P < .05). CONCLUSION: Maternal type 2 diabetes
mellitus induces cardiac hypertrophy in embryonic hearts. Adverse cardiac
remodeling, including elevated collagen synthesis, suppressed fibronectin
synthesis, profibrosis, and apoptosis, is implicated as the etiology of cardiac
hypertrophy.
PMID- 28412089
TI - Inverse association between negative symptoms and body mass index in chronic
schizophrenia.
AB - BACKGROUND: We investigated whether negative symptoms, such as poor motivation or
anhedonia, were associated with higher body mass index (BMI) in stable patients
with schizophrenia chronically treated with antipsychotic medication. METHODS: 62
olanzapine- or clozapine-treated patients with illness duration of at least four
years were selected from an international multicenter study on the
characterization of negative symptoms. All participants completed the Brief
Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale
(PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were
explored, as well as multiple regression analyses. We further explored the
association of two principal component factors of the BNSS and BMI. Subsidiary
analyses re-modeled the above using the negative symptoms subscale of the PANSS
and the EMSLEY factor for negative symptoms for convergent validity. RESULTS:
Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31;
p=0.015). A multiple regression analysis showed that negative symptoms (BNSS
score) and age were significant predictors of BMI (p=0.037). This was mostly
driven by the motivation/pleasure factor of the BNSS. Within this second factor,
BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality
(r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was
positively associated with BNSS (r=0.873, p<0.001), but negatively associated
with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach
significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative
symptoms were associated with higher BMI (assessed using both the BNSS and
EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia
and asociality levels.
PMID- 28412090
TI - Pituitary gland in Bipolar Disorder and Major Depression: Evidence from
structural MRI studies: Special Section on "Translational and Neuroscience
Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This
Section of JAD focuses on the relevance of translational and neuroscience studies
in providing a better understanding of the neural basis of affective disorders.
The main aim is to briefly summarise relevant research findings in clinical
neuroscience with particular regards to specific innovative topics in mood and
anxiety disorders.
AB - BACKGROUND: The function of the hypothalamo-pituitary-adrenal axis (HPA) has been
widely investigated in mood disorders based on its role in regulating stress
response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored
pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder
(MDD). In this context, the present review summarizes the results from MRI
studies with the final aim of commenting on the presence of common or distinct PG
structural alterations between these two disabling illnesses. METHODS: A
bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and
MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was
performed. RESULTS: Following the screening process of the available literature
it can be said that a) PG enlargement has been found in both BD and MDD,
therefore potentially representing a common neurobiological marker characterizing
mood disorders, and b) PG volumes are moderated by age and sex in both illnesses,
although the direction and the extent of this moderation are still not fully
clear. LIMITATIONS: Few MRI studies with heterogeneous results. CONCLUSIONS:
These hypotheses must be taken with caution especially because the heterogeneity
of the results of the studies reviewed does not allow for a definite answer about
the role of PG in affective disorders. Therefore, larger longitudinal studies
investigating PG volumes in BD and MDD patients at the early phases of the
illness, by considering females and males separately, are needed to further
corroborate these findings.
PMID- 28412091
TI - Lansoprazole halts contrast induced nephropathy through activation of Nrf2
pathway in rats.
AB - Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury
characterized by significant mortality and morbidity. To date, there is no
successful protective regimen for CIN especially in poor kidney function
patients. Lansoprazole has been shown to exert antioxidant action through
induction of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. The aim
of the present study is to investigate the potential of lansoprazole to activate
Nrf2 pathway in the kidney and consequently to protect against oxidative stress
induced by iodinated contrast media. Lansoprazole, at a dose of 100 mg/kg, showed
a significant induction of Nrf2 mRNA after 3 h. Administration of contrast media
induced significant increase in serum creatinine and blood urea nitrogen,
histological deterioration, and reduction in total antioxidant capacity.
Moreover, it instigated the defensive Nrf2 gene expression and immunoreactivity.
In addition, there were overexpression of HO-1, caspase 3, p53 and IL6 genes and
downregulation of Bcl2 gene. Pre-treatment with lansoprazole (100 mg/kg)
ameliorated the nephrotoxicity parameters and oxidative stress, improved
histological lesions, and hijacked apoptotic and inflammatory markers that were
provoked by contrast media. In conclusion, lansoprazole attenuates experimental
CIN which might be due to activation of Nrf2 antioxidant defence pathway. These
findings highlight the potential benefit of incorporating lansoprazole in the
protective regimen against CIN especially for susceptible patients.
PMID- 28412092
TI - Chaotic oscillations of gas bubbles under dual-frequency acoustic excitation.
AB - Chaotic oscillation of bubbles in liquids reduces the efficiency of the
sonochemical system and should be suppressed in the practical applications. In
the present paper, a chaos control method based on the dual-frequency approach is
numerically investigated and is proved to be an effective method even for cases
with intensive energy input. It was found that the chaos could be successfully
suppressed by the application of dual-frequency approach in a wide range of
parameter zone (even with high acoustic pressure amplitude). Furthermore,
influences of power allocation between two waves on the chaos control are
quantitatively discussed with clear descriptions of the routes from stable
oscillations to chaos.
PMID- 28412093
TI - Non-Small Cell Lung Cancer as a Second Primary Among Patients With Previous
Malignancy: Who Is at Risk?
AB - BACKGROUND: Patients with previous malignancies could be at increased risk of non
small cell lung cancer (NSCLC). However, the extent of the risk is unknown for
many cancer types; thus, it is unclear who might benefit from screening.
MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results data set
from 1992 to 2012 was used to identify patients with previous malignancies who
received a diagnosis of NSCLC >= 6 months after their initial cancer diagnosis.
Standardized incidence ratios (SIRs) for NSCLC were calculated as a ratio of the
observed to expected cases adjusted by person-years at risk. Cancers with a SIR >
1.0 had a risk of NSCLC greater than expected. The analyses were stratified by
sex, radiation therapy use, and histologic type. RESULTS: Among the cancer
survivors, 32,058 developed NSCLC. Smoking-related (lung, head and neck, bladder)
and hematologic malignancies, regardless of previous radiation therapy, had the
greatest SIR for NSCLC (range, 1.97-4.88). Colorectal and renal cancer survivors
also had an increased SIR for NSCLC (1.16 and 1.21, respectively). Women with
previous pancreatic cancer treated with radiation, breast cancer with or without
radiation therapy, and those with thyroid cancer demonstrated a greater SIR for
lung adenocarcinoma. Men with previous irradiated prostate cancer also had an
elevated SIR (1.08; 99% confidence interval, 1.01-1.15) for lung adenocarcinoma.
Patients with melanoma, prostate or uterine cancer had a lower SIR for NSCLC than
expected. CONCLUSION: Smoking-related malignancies had the greatest risk of
NSCLC. Radiation therapy conferred an elevated risk of NSCLC for certain cancers.
Melanoma, prostate, and uterine cancer survivors had a low risk of NSCLC. These
results could help identify high-risk screening candidates in the growing
population of cancer survivors.
PMID- 28412094
TI - Emotional Problems, Quality of Life, and Symptom Burden in Patients With Lung
Cancer.
AB - OBJECTIVES: Lung cancer is associated with a greater symptom burden than other
cancers, yet little is known about the prevalence of emotional problems and how
emotional problems may be related to the physical symptom burden and quality of
life in newly diagnosed patients with lung cancer. This study aimed to identify
the patient and disease characteristics of patients with lung cancer experiencing
emotional problems and to examine how emotional problems relate to quality of
life and symptom burden. PATIENTS AND METHODS: A total of 2205 newly diagnosed
patients with lung cancer completed questionnaires on emotional problems, quality
of life, and symptom burden. RESULTS: Emotional problems at diagnosis were
associated with younger age, female gender, current cigarette smoking, current
employment, advanced lung cancer disease, surgical or chemotherapy treatment, and
a lower Eastern Cooperative Oncology Group performance score. Additionally,
strong associations were found between greater severity of emotional problems,
lower quality of life, and greater symptom burden. CONCLUSION: Certain
characteristics place patients with lung cancer at greater risk for emotional
problems, which are associated with a reduced quality of life and greater symptom
burden. Assessment of the presence of emotional problems at the time of lung
cancer diagnosis provides the opportunity to offer tailored strategies for
managing negative mood, and for improving the quality of life and symptom burden
management of patients with lung cancer.
PMID- 28412095
TI - The pathology associated with diabetic retinopathy.
AB - This review summarizes the pathological features of diabetic retinopathy. The
lesions occurring in the diabetic retina have been described over many decades
using descriptive and experimental approaches based on clinical studies on
patients, human post-mortem material, animal models and various in vitro systems.
We have also accumulated a wealth of knowledge about basic molecular mechanisms
and key pathogenic processes that drive these abnormalities in diabetic retina.
Despite these advances, there are still limited therapeutic options for diabetic
retinopathy with those currently available only addressing late-stage disease.
With a particular focus on the earlier stages of diabetes, there is growing
appreciation the complex neuronal, glial and microvascular abnormalities which
progressively disrupt retinal function. This is especially true from the
perspective of the neurovascular unit during health and disease. Based on a
strong appreciation of cellular and molecular pathology that underpins diabetic
retinopathy, further advances are anticipated as we drive towards development of
efficacious therapeutic options that can address all stages of disease.
PMID- 28412096
TI - Evolution of saturated hydraulic conductivity with compression and degradation
for municipal solid waste.
AB - Municipal solid waste (MSW) specimens were created from synthetic fresh MSW
degraded in a laboratory scale enhanced degradation reactor. The degree of
degradation and saturated hydraulic conductivity ks were measured to study the
effects of compression and degradation on ks of MSW. The degree of degradation
was characterized through the ratio of cellulose content to lignin content (i.e.,
C/L) and the loss ratio of volatile solid (i.e., DOD). ks of MSW specimens with
different degrees of degradation was measured through triaxial permeameter tests
under different confining pressures. It was found that, when the degradation time
increased from 0month to 18months, ks decreased less than 1 order of magnitude
for specimens with the same porosity (i.e., n=0.63 or 0.69). However, for
specimens with the same degradation time, the decrease of ks could reach 2 orders
of magnitude with n decreasing from 0.8 to 0.6. It indicates that compression has
much greater influence on the reduction of ks than that of degradation. Based on
the Kozeny-Carman model and first-order kinetics, a prediction model related to n
and C/L (or DOD) of MSW was proposed to analyze the evolution of ks with
compression and biodegradation. The methods to determine the values of model
parameters were also proposed.
PMID- 28412097
TI - Optimization and characterization of hydrochar produced from microwave
hydrothermal carbonization of fish waste.
AB - Fish processing results in large amounts of solid and liquid wastes that are
unsustainably dumped into oceans and landfills. Alternative sustainable
technologies that completely utilize seafood wastes are needed. Hydrothermal
carbonization (HTC) that converts moisture-rich biomass into hydrochar is mostly
employed for pure lignocellulosic biowaste. However, the suitability of HTC for
pure non-lignocellulosic waste is unknown. Here, for the first time, a response
surface design guided optimization of microwave hydrothermal carbonization (MHTC)
process parameters, holding temperature (150-210 degrees C) and time (90-120min),
showed that a temperature of approximately 200 degrees C and a time of
approximately 119min yielded maximal hydrochar (~34%). The atomic carbon and ash
content, and calorific value of hydrochar were approximately 25-57%, 20-28%, and
19-24.5MJ/kg respectively, depending on the MHTC operating conditions. Taken
together, these results confirm that MHTC produces hydrochar from fish waste of
quality comparable to one produced from certain lignocellulosic, sewage and
municipal wastes. Therefore, this strategy presents an exciting alternative
technology that can be used either independently or in combination with other
valorization techniques to completely utilize fish wastes irrespective of their
quality.
PMID- 28412098
TI - Supply and demand of some critical metals and present status of their recycling
in WEEE.
AB - New development and technological innovations make electrical and electronic
equipment (EEE) more functional by using an increasing number of metals,
particularly the critical metals (e.g. rare and precious metals) with specialized
properties. As millions of people in emerging economies adopt a modern lifestyle,
the demand for critical metals is soaring. However, the increasing demand causes
the crisis of their supply because of their simple deficiency in the Earth's
crust or geopolitical constraints which might create political issues for their
supply. This paper focuses on the sustainable supply of typical critical metals
(indium, rare earth elements (REEs), lithium, cobalt and precious metals) through
recycling waste electrical and electronic equipment (WEEE). To illuminate this
issue, the production, consumption, expected future demand, current recycling
situation of critical metals, WEEE management and their recycling have been
reviewed. We find that the demand of indium, REEs, lithium and cobalt in EEE will
continuously increasing, while precious metals are decreasing because of new
substitutions with less or even without precious metals. Although the generation
of WEEE in 2014 was about 41.9 million tons (Mt), just about 15% (6.5 Mt) was
treated environmentally. The inefficient collection of WEEE is the main obstacle
to relieving the supply risk of critical metals. Furthermore, due to the
widespread use in low concentrations, such as indium, their recycling is not just
technological problem, but economic feasibility is. Finally, relevant
recommendations are point out to address these issues.
PMID- 28412100
TI - Risk of Acute Kidney Injury after Percutaneous Pharmacomechanical Thrombectomy
Using AngioJet in Venous and Arterial Thrombosis.
AB - BACKGROUND: Percutaneous mechanical thrombectomy is commonly used to treat acute
thrombotic syndromes. AngioJet (AJ) forcibly sprays fibrinolytics to fragment and
aspirate thrombus. It is known to cause hemolysis and gross hematuria, yet
potential consequences to renal function after AJ remain unstudied. We sought to
determine the risk of acute kidney injury (AKI) after AJ when compared with other
lysis techniques. METHODS AND RESULTS: We retrospectively reviewed patients
treated with thrombolysis over 5 years. We identified those treated with AJ or
catheter-directed thrombolysis (CDT). Demographics, indications, procedures, and
laboratory values within 3 days were recorded. AKI was defined as an increase
>25% above the baseline creatinine within 72 hr of the procedure. IN total, 102
patients (52 AJ, 50 CDT) had no statistical difference in mean age (50 and 51),
indication (arterial thrombosis 65% and 88%), or baseline creatinine (0.9 and 1.0
mg/dL), respectively. AKI occurred in 15 (29%) patients treated with AJ versus 4
(8%) of CDT (P = 0.007). Similar numbers of AJ and CDT patients underwent
additional open surgical procedures (21% and 30%, respectively, P = not
significant). Multivariable analysis demonstrated that the odds of AKI were only
increased by AJ (odds ratio [OR] 8.2, 95% confidence interval [CI] 1.98-34.17, P
= 0.004), open surgery (OR 5.4, 95% CI 1.43-20.17, P = 0.013), or a >10% drop in
hematocrit (OR 4.0, 95% CI 1.15-14.25, P = 0.03). CONCLUSIONS: In our
observational study, AJ is an independent risk factor for AKI. Concomitant open
surgery and drop in hematocrit also raise the odds of AKI. Renal injury after AJ
is under-reported in the literature, and may be related to hemolysis from the
device.
PMID- 28412099
TI - Tumor Cell Invadopodia: Invasive Protrusions that Orchestrate Metastasis.
AB - Invadopodia are a subset of invadosomes that are implicated in the integration of
signals from the tumor microenvironment to support tumor cell invasion and
dissemination. Recent progress has begun to define how tumor cells regulate the
plasticity necessary for invadopodia to assemble and function efficiently in the
different microenvironments encountered during dissemination in vivo. Exquisite
mapping by many laboratories of the pathways involved in integrating diverse
invadopodium initiation signals, from growth factors, to extracellular matrix
(ECM) and cell-cell contact in the tumor microenvironment, has led to insight
into the molecular basis of this plasticity. Here, we integrate this new
information to discuss how the invadopodium is an important conductor that
orchestrates tumor cell dissemination during metastasis.
PMID- 28412101
TI - Genetics of recurrent miscarriage and fetal loss.
AB - Despite years of research, miscarriage, particularly when recurrent, continues to
pose a medical challenge. An embryo chromosomal error is responsible for 50-60%
of recurrent cases; however, up to 30-50% remains an enigma. Successful pregnancy
involves different maternal physiologic changes and certain complex interactions
between the fetus and the mother by cytokines, angiogenic mediators and hormones.
To date, research lines have focused on genetic and epigenetic polymorphisms
related mainly to immune response and inflammatory mediators, and have yielded a
significant relationship between recurrent miscarriage and immune mechanisms.
Thus, unknown causes of miscarriage could be due to an immune imbalance induced
by T-helper Th1/Th2/Th17 cytokines and regulatory T cells. Furthermore, these
genes and mediators have long been suspected of being blood markers for the
clinical diagnosis and management of miscarriage; however, more evidence is
required for them to be included in medical practice and obstetric guidelines.
PMID- 28412102
TI - The method of urine sampling is not a valid predictor for vesicoureteral reflux
in children after febrile urinary tract infections.
AB - INTRODUCTION: The likelihood of detecting vesicoureteral reflux (VUR) after
febrile urinary tract infections (UTI) in children logically should correlate
with the correct diagnosis of the UTI. Beneath the unspecific symptoms of fever
urine analysis is the main diagnostic criterion for the exact diagnosis of
febrile UTIs in children. Use of inadequate urine sampling techniques during
diagnosis may lead to impaired accuracy in UTI diagnosis. This could lead to the
assumption that children, having diagnosed their UTI by the use of possibly
inadequate urine sampling techniques should not be evaluated as consequently
compared to those, where the diagnosis relied on sterile urine sampling
techniques. We hypothesized that children with possibly contaminated urine
samples during the initial diagnosis may show a lower rate of VUR in subsequent
VCUGs because of a wrong diagnosis initially compared to children, where accurate
urine sampling techniques were used. PATIENTS: Between 2009 and 2014, a total of
555 patients underwent a primary VCUG at our department indicated because of
febrile UTIs. Patients with urine collection methods other than bag urine and
catheter/suprapubic aspiration (SPA) were excluded from this study (mid-stream
urine, potty urine, n = 149). We evaluated 402 patients (male/female 131/271,
mean age 1.91 years), VUR rates and grades were compared between patients where
urine was sampled by the use of a urine bag only at the time of diagnosis (n =
296, 73.6%) and those where sterile urine sampling (catheter, suprapubic
puncture) was performed (n = 106, 26.3%). 4 patients were excluded due to
equivocal data on urine sampling. RESULTS: VUR rate in children after sterile
urine sampling using a catheter or SPA accounted to 31.1%. In those where urine
samples acquired by the use of urine bags were used, 33.7% showed VUR on
subsequent VCUG (p = 0.718). There were no significant differences as to VUR
grades or gender, although VUR was much more commonly diagnosed in female
patients (37.0% vs 28.2%, p = 0.227) (Figure). CONCLUSION: Children diagnosed
with their UTI by use of bag urine in our experience carried the same risk of
showing a VUR in a subsequent VCUG compared to those, where the initial diagnosis
relied - beneath clinical criteria - on urine samples acquired by suprapubic
puncture or catheterization. Consequently urine-sampling technique during initial
UTI diagnosis alone should not be used as predictor for the reliability of UTI
diagnosis and should not influence the further management after UTI.
PMID- 28412103
TI - Reverse shoulder arthroplasty compared with hemiarthroplasty in the treatment of
acute proximal humeral fractures.
AB - BACKGROUND: Complex proximal humeral fractures may require prosthetic replacement
of the humeral head. Surgical options include reverse shoulder arthroplasty (RSA)
and shoulder hemiarthroplasty; however, the optimal technique remains
controversial. The goal of this study was to compare functional outcomes and
revision rates of RSA with hemiarthroplasty in patients with acute proximal
humeral fractures. MATERIALS AND METHODS: Between January 1, 1999, and December
31, 2014, there were 218 patients who underwent RSA and 427 who underwent
hemiarthroplasty for acute proximal humeral fractures identified through New
Zealand Joint Registry records. Study groups were compared with regard to
baseline characteristics, operative characteristics, and postoperative outcomes
(Oxford Shoulder Score [OSS], revision rate, mortality rate) at 6 months and 5
years after surgery. RESULTS: RSA patients were significantly older (mean age,
78.2 vs. 71.6 years; P < .001), with a higher proportion of female patients (90%
vs. 77%; P < .001) than in the hemiarthroplasty group. No statistically
significant difference existed in revision rate per 100 component-years (0.58
[RSA] vs. 1.16 [hemiarthroplasty]; P = .137) or 1-year mortality (3.8% vs. 3.4%;
P = .805) between both groups. There was no significant difference in 6-month OSS
(29.6 vs. 28.4; P = .305). The RSA group demonstrated a superior mean 5-year OSS
(37.6 vs. 32.7; P = .078); however, the difference did not achieve statistical
significance. CONCLUSIONS: Although our results suggest that RSA patients may
experience superior 5-year functional scores, we have identified no significant
difference in functional outcomes and revision rates between RSA and
hemiarthroplasty in the treatment of acute proximal humeral fractures.
PMID- 28412104
TI - Cement stress predictions after anatomic total shoulder arthroplasty are
correlated with preoperative glenoid bone quality.
AB - HYPOTHESIS: We hypothesized that biomechanical parameters typically associated
with glenoid implant failure after anatomic total shoulder arthroplasty (aTSA)
would be correlated with preoperative glenoid bone quality. METHODS: We developed
an objective automated method to quantify preoperative glenoid bone quality in
different volumes of interest (VOIs): cortical bone, subchondral cortical plate,
subchondral bone after reaming, subchondral trabecular bone, and successive
layers of trabecular bone. Average computed tomography (CT) numbers (in
Hounsfield units [HU]) were measured in each VOI from preoperative CT scans. In
parallel, we built patient-specific finite element models of simulated aTSAs to
predict cement stress, bone-cement interfacial stress, and bone strain around the
glenoid implant. CT measurements and finite element predictions were obtained for
20 patients undergoing aTSA for primary glenohumeral osteoarthritis. We tested
all linear correlations between preoperative patient characteristics (age, sex,
height, weight, glenoid bone quality) and biomechanical predictions (cement
stress, bone-cement interfacial stress, bone strain). RESULTS: Average CT numbers
gradually decreased from cortical (717 HU) to subchondral and trabecular (362 HU)
bone. Peak cement stress (4-10 MPa) was located within the keel hole, above the
keel, or behind the glenoid implant backside. Cement stress, bone-cement
interfacial stress, and bone strain were strongly negatively correlated with
preoperative glenoid bone quality, particularly in VOIs behind the implant
backside (subchondral trabecular bone) but also in deeper trabecular VOIs.
CONCLUSION: Our numerical study suggests that preoperative glenoid bone quality
is an important parameter to consider in aTSA, which may be associated with
aseptic loosening of the glenoid implant. These initial results should now be
confronted with clinical and radiologic outcomes.
PMID- 28412105
TI - How bone quality may influence intraoperative and early postoperative problems
after angular stable open reduction-internal fixation of proximal humeral
fractures.
AB - BACKGROUND: With the introduction of the deltoid tuberosity index (DTI), a simple
radiographic tool has become available to measure bone mineral density of the
proximal humerus. The aim of this study was to assess the influence of local bone
mineral density on the early failure rate after angular stable open reduction
internal fixation of proximal humeral fractures (PHFs). METHODS: We
retrospectively followed up all patients treated with angular stable implants for
PHFs from 2007 to 2014. The fractures were classified according to Neer, and the
DTI, metaphyseal head extension (MHE), medial hinge displacement, and quality of
reduction were assessed. Failures were defined as head screw cutouts. RESULTS:
The study included 146 patients (mean age, 66 years; range, 20-94 years). The
mean follow-up period was 11 months (range, 3-94 months). Of the fractures, 91%
were classified as 2- or 3-part fractures and 9% as 4-part fractures. The mean
DTI was 1.44 (range, 1.19-2.11), and the mean MHE was 12 mm (range, 0-48 mm). The
reduction result was at least acceptable in 80% of fractures. Screw cutouts were
found in 23%. The DTI and MHE were the most significant preoperative predictors
for the reduction result. The DTI (P = .036) and age (P = .02) were independent
preoperative factors, and a good reduction (P = .001) was the only intraoperative
factor influencing cutout. DISCUSSION: This study proves that good bone quality
and a long MHE are helpful for the reduction. Furthermore, good bone quality, a
younger age, and a good reduction prevent later cutout. We conclude that local
bone quality is a relevant factor in the treatment plan for PHFs.
PMID- 28412106
TI - Radial notch labralization for proximal radioulnar joint dysplasia.
AB - BACKGROUND: Chronic posterior subluxation or dislocation of the radial head is
uncommon and difficult to treat. To restore radiocapitellar alignment, procedures
such as deepening of the notch using a high-speed burr have been described, but
they can result in cartilage damage. We hypothesized that a radial notch
labralization using soft tissue could improve radiocapitellar tracking without
violating the joint surface. METHODS: A radial notch labralization was performed
in 3 patients with chronic posterior subluxation of the radial head and
developmental dysplasia of the radial notch in the setting of complex recurrent
instability of the elbow. A soft tissue graft (typically a portion of an
allograft hamstring tendon) was used to create a meniscus-like bumper
posteriorly, thereby deepening the radial notch and reducing its radius of
curvature. A corrective anterior opening wedge ulnar osteotomy was also performed
to realign the radial head with the capitellum. RESULTS: At a mean follow-up of
32 months, all 3 patients were pain free and had maintained a stable joint, with
a functional range of motion. Each patient gave a rating of either "Greatly
Improved" or "Almost Normal" on the Summary Outcome Determination scale.
Radiographs performed during the last follow-up showed improved radiocapitellar
alignment. CONCLUSION: Chronic posterior subluxation or dislocation of the radial
head can occur subsequent to developmental joint changes. The radial notch
labralization using a soft tissue graft associated with a corrective ulnar
osteotomy was successful in restoring radial head stability and avoiding
cartilage damage.
PMID- 28412107
TI - Glenoid morphology in obstetrical brachial plexus lesion: a three-dimensional
computed tomography study.
AB - BACKGROUND: Obstetric brachial plexus lesion (OBPL) frequently leads to
glenohumeral dysplasia, and excessive retroversion of the glenoid is among the
best known developmental disturbances. Most analyses of the glenoid are based on
2-dimensional (D) imaging and do not address glenoid inclination or provide
information on the glenoid in the sagittal plane. We aim to describe the 3-D
deformity of the glenoid in children with OBPL. METHODS: Preoperative computed
tomography (CT) scans of the nonaffected and the affected scapula of 24 children
(aged 5 to 12 years) with developmental disturbances after OBPL years were
analyzed. The dimensions of the scapula and the deformation of the glenoid were
visualized in 3-D. RESULTS: The retroversion of the glenoid fossa was greater in
all affected shoulders, and 2-D measurements significantly overestimated
retroversion compared with angles measured in 3-D. The inclination of the glenoid
fossa was altered, and a distal bony edge loss was observed on 3-D reformations
in the sagittal plane. The reliability of the measured angles was excellent, and
the kappa agreement for the description of the glenoid form was substantial.
Furthermore, the dimensions of the scapula were significantly smaller on the
affected shoulders. CONCLUSION: OBPL is indeed a 3-D disorder. Our measurements
revealed excessive retroversion of the glenoid fossa, and the reliability of the
3-D CT measurements was superior to their 2-D counterparts. 3-D CT reformations
of the glenoid in the coronal and the sagittal plane added further to 3-D
understanding of glenoid morphology in OBPL. These new findings legitimatize a 3
D CT-based description of the glenoid deformities connected with OPBL.
PMID- 28412108
TI - Emergence of the arterial switch procedure for transposition of the great
arteries and the potential cost of surgical innovation.
PMID- 28412110
TI - Change of paradigm or change of heart?
PMID- 28412109
TI - Reengineering valve patients' postdischarge management for adapting to bundled
payment models.
AB - BACKGROUND: Bundled Payments for Care Improvement (BPCI) initiatives were
developed by Medicare in an effort to reduce expenditures while preserving
quality of care. Payment model 2 reimburses based on a target price for 90-day
episode of care postprocedure. The challenge for valve patients is the
historically high (>35%) 90-day readmission rate. We analyzed our institutional
cardiac surgical service line adaptation to this initiative. METHODS: On May 1,
2015, we instituted a readmission reduction initiative (RRI) that included
presurgical risk stratification, comprehensive predischarge planning, and
standardized postdischarge management led by cardiac nurse practitioners (CNPs)
who attempt to guide any postdischarge encounters (PDEs). A prospective database
also was developed, accruing data on all cardiac surgery patients discharged
after RRI initiation. We analyzed detailed PDEs for all valve patients with
complete 30-day follow-up through November 2015. RESULTS: Patients included 219
surgical patients and 126 transcatheter patients. Sixty-four patients had 79
PDEs. Of these 79 PDEs, 46 (58.2%) were guided by CNPs. PDEs were due to fluid
overload/effusion (21, 27%), arrhythmia (17, 22%), bleeding/thromboembolic events
(13, 16%), and falls/somatic complaints (12, 15%). Thirty-day readmission rate
was 10.1% (35/345). Patients with transcatheter aortic valve replacement had a
higher rate of readmission than surgical patients (15.0% vs 6.9%), but were older
with more comorbidities. The median readmission length of stay was 2.0 days
(interquartile range 1.0-5.0 days). Compared with 2014, the 30-day readmission
rate for BPCI decreased from 18% (44/248) to 11% (20/175), P = .05. CONCLUSIONS:
Our reengineering of pre/postdischarge management of BPCI valve patients under
tight CNP control has significantly reduced costly 30-day readmissions in this
high-risk population.
PMID- 28412111
TI - Apneic oxygen insufflation decreases the incidence of hypoxemia during one-lung
ventilation in open and thoracoscopic pulmonary lobectomy: A randomized
controlled trial.
AB - OBJECTIVE: Hypoxemia is common during one-lung ventilation (OLV) for thoracic
surgery. When hypoxemia occurs, surgery is interrupted for rescue ventilation.
Apneic oxygen insufflation (AOI), which provides O2 without applying pressure,
may prevent hypoxemia and does not interrupt surgery. The aim of this study was
to determine the effectiveness of the AOI technique for preventing hypoxemia
during OLV in thoracic surgery. METHODS: Patients undergoing open or
thoracoscopic pulmonary lobectomy from September to December 2015 were included.
Patients were assigned randomly to a non-AOI group or an AOI group (n = 45 each).
OLV was initiated and at the 15-minute mark (OLV15), patients in the AOI group
received oxygen insufflation at 3 L/min to the nonventilated lung for 30 minutes
(OLV45). The primary endpoint was the occurrence of hypoxemia (SaO2 <90%) during
OLV. RESULTS: The demographic and operative data were similar between the 2
groups. The incidence of hypoxemia was greater in the non-AOI than the AOI group
(18% vs 0%; P = .009). DeltaPaO2 (the difference in partial pressure of oxygen in
arterial blood between OLV 45 and 15 minutes) was smaller in the AOI than the non
AOI group (-29 mm Hg vs -69 mm Hg; P = .005). Duration of surgery and incidence
of complications did not vary between groups. CONCLUSIONS: AOI decreases the
incidence of hypoxemia and improves arterial oxygenation during OLV for open and
thoracoscopic surgery. AOI may be a valuable option to prevent hypoxemia. It can
be used before relying on continuous positive airway pressure or intermittent two
lung ventilation and result in fewer interruptions in surgery.
PMID- 28412112
TI - During one-lung ventilation, K.I.S.S.-Keep It Simple Surgeons.
PMID- 28412113
TI - The half-turned truncal switch operation adds a new spin for patients with
complex coronary anatomy and transposition of the great arteries.
PMID- 28412114
TI - Vascular rings: To scope or not to scope.
PMID- 28412115
TI - Outcome of isolated aortic valve replacement in patients with classic and
paradoxical low-flow, low-gradient aortic stenosis.
AB - OBJECTIVE: To analyze operative outcomes and mid-term results after isolated
aortic valve replacement (AVR) in low-flow, low-gradient aortic stenosis (LFLG
AS) by comparing the 2 subcategories (classic low-flow, low-gradient aortic
stenosis [CLFLG] and paradoxical low-flow, low-gradient aortic stenosis [PLFLG]).
METHODS: This was a retrospective analysis of prospectively collected data for
all isolated AVR in LFLG AS performed in our center during the last 13 years (n =
198; CLFLG AS, n = 66, 33% and PLFLG AS, n = 132, 67%). Median follow-up was 3.7
+/- 3.3 years. RESULTS: Preoperative mean gradient was 30.2 +/- 8.8 mm Hg in the
CLFLG AS group and 31.4. +/- 7.0 mmHg in the PLFLG AS group (P = .001). Female
sex, hypertension, and neurologic and renal disease were more frequent in the
PLFLG AS group (P < .01) whereas advanced New York Heart Association class,
atrial fibrillation, and pulmonary hypertension were more frequent in the CLFLG
AS group (P < .01). In-hospital mortality was 3% in the CLFLG AS group and 2.3%
in the PLFLG AS group, P = .08. One- and five-year mortality rates were
significantly greater in the CLFLG AS group (27% and 42% vs 6% and 20% in the
PLFLG AS group, respectively, P = .001). On follow-up, 90% of the total survivors
were in New York Heart Association class I-II, and 51% of the patients in the
CLFLG AS group had an improvement in their ventricular function. CONCLUSIONS: AVR
can be performed in LFLG AS with low in-hospital mortality. CLFLG AS carries
similar in-hospital mortality to PLFLG AS but greater mid-term mortality. Surgery
provided excellent functional status among survivors.
PMID- 28412116
TI - Is new-onset postoperative atrial fibrillation a benign complication?
PMID- 28412117
TI - Bigger is not always better.
PMID- 28412119
TI - I am at my best when I slow down and that is what I will teach my trainees!
PMID- 28412118
TI - Main stem bronchus surgery with pulmonary preservation.
PMID- 28412120
TI - Single lymph node metastasis 10 years after radical resection of a thymoma.
PMID- 28412121
TI - HeartMate 3: Better...but not perfect.
PMID- 28412122
TI - Coronary artery disease is associated with an increased mortality rate following
video-assisted thoracoscopic lobectomy.
AB - OBJECTIVE: To compare the incidence of major adverse cardiac events (MACE) and
mortality following video-assisted thoracoscopic surgery (VATS) lobectomy in
patients with and without coronary artery disease (CAD). METHODS: Multicentre
retrospective analysis of 1699 patients undergoing VATS lobectomy (January 2012
March 2015). CAD definition: previous acute myocardial infarct (AMI), angina,
percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).
MACE definition: postoperative acute myocardial ischemia, cardiac arrest or any
cardiac death. Propensity score analysis was performed to match patients with and
without CAD. Outcomes of the 2 matched groups were compared. RESULTS: The
incidence of MACE and mortality for the entire population was 0.4% (7 patients)
and 1.7% (29 patients); 218 patients (13%) had a history of CAD: 106 previous
AMI, 55 angina, 32 CABG, and 81 PCI. The propensity score yielded 2 well-balanced
groups of 218 pairs with and without CAD. MACE (CAD 2 [0.9%] vs no-CAD 1 [0.5%];
P = 1), cardiovascular and pulmonary complications (CAD 61 [28%] vs no-CAD 51
[23%]; P = .3) and postoperative stay (CAD 7.3 days vs no-CAD 6.2 days; P = .3)
were not different between the groups. The incidence of atrial fibrillation (CAD
31 [14%] vs no-CAD 18 [8.2%]; P = .07), 30-day mortality (CAD: 11 [5%] vs no-CAD
2 [0.9%]; P = .02) and death among complicated patients (CAD 18% vs no-CAD 3.9%;
P = .009) were higher in the CAD group. CONCLUSIONS: The incidence of MACE
following VATS lobectomy in patients with CAD is low and similar to patients
without CAD. However, their risk of postoperative mortality is fivefold higher
compared with non-CAD patients, warranting refined preoperative functional
evaluation and more intense postoperative monitoring.
PMID- 28412123
TI - Discussion.
PMID- 28412124
TI - Time for randomization.
PMID- 28412125
TI - Is gout an easy-to-treat disease? The importance of health determinants.
PMID- 28412126
TI - Gender-specific differences and burn outcome.
PMID- 28412127
TI - Consideration of the use of commercial flights to transfer patients with burns.
PMID- 28412128
TI - The official update of the POSAS: An invitation to share experiences to improve
the POSAS in 'Project POSAS 3.0'.
PMID- 28412129
TI - Acute kidney injury after burn.
AB - Acute kidney injury (AKI) is a common and morbid complication after severe burn,
with an incidence and mortality as high as 30% and 80%, respectively. AKI is a
broad clinical condition with many etiologies, which makes definition and
diagnosis challenging. The most recent Kidney Disease: Improving Global Outcomes
(KDIGO) consensus guidelines defined stage and severity of AKI based on changes
of serum creatinine and urine output (UOP) across time. Burn-related kidney
injury is typically classified as early (0-3days after injury) or late (4-14days
after injury). Early burn AKI is typically due to hypovolemia, poor renal
perfusion, direct cardiac suppression from TNF-alpha, and precipitation of
denatured proteins, while late AKI is often due to sepsis, multi-organ failure,
and nephrotoxic drugs. Diagnosis can be difficult as UOP and biochemical markers
can be relatively normal even with significant renal injury. A sensitive and
specific biomarker for the early diagnosis of AKI is sorely needed, and multiple
potential biomarkers are being investigated. For treatment, the reversal of the
underlying cause is the first intervention. The advent of renal replacement
therapy has significantly improved the mortality of burn patients with AKI and
should be initiated early if injury progresses despite initial maneuvers.
Unfortunately, no beneficial pharmacologic agents have been identified, despite
multiple investigations. Of burn patients who survive AKI, the vast majority do
not receive long-term hemodialysis and they are generally thought to have a good
renal prognosis although this view is shifting. Preliminary data in the burn
population suggest that AKI may confer an increased risk of end-stage renal
disease and long-term all-cause mortality, but further research is needed.
PMID- 28412130
TI - Early excision and grafting (EE&G): Opportunity or threat?
PMID- 28412131
TI - Screening nasal swabs for methicillin resistant Staphylococcus aureus: A regional
burn center's experience.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that
can result in substantial morbidity and mortality. Early detection of MRSA
colonization by screening nasal swabs may be important in the management of burn
injured patients. However, studies examining its use in this population are
limited. The aim of this study was to study the utility of admission MRSA
screening nasal swabs and determine if being positive for MRSA on admission
impacted outcomes. MATERIALS AND METHODS: A retrospective review was conducted of
burn patients who presented to a single regional burn center between June 2012
and December 2014. Electronic medical records and charts were reviewed for
patient demographics and management. MRSA screening swabs were obtained from the
anterior nares of burn patients upon admission. Patients without a MRSA nasal
swab within 48h of admission were excluded. Outcomes analyzed included overall
length of stay, ICU admission and length of stay, mechanical ventilation,
procedure count, time to excision, and wound complications after normalizing to
total body surface area burn size (%TBSA). RESULTS: During the study period, 601
patients received a MRSA screening nasal swab upon admission. Of these, 24
patients screened positive for MRSA (4%). Patients who screened positive for MRSA
had a significantly increased mean length of stay (3.95v 2.36 days; p<0.05) and
number of surgical procedures (1.92v 1.06; p<0.05). Positively screened patients
also had a higher proportion of wound infections (50% v 18.2%; p<0.05), half of
which were caused by MRSA. Subsequent graft complications were seen in 50% of
patients with a wound complication. Only 2 positively screened patients were
started on empiric antibiotics. CONCLUSIONS: Burn patients who screened positive
for MRSA had greater lengths of stay, more surgical procedures, and higher wound
complications. Early identification of MRSA colonized patients in this patient
population might allow for treatment modifications that improve outcomes. Further
study is warranted in a prospective clinical trial.
PMID- 28412132
TI - Pre-existing psychiatric disorder in the burn patient is associated with worse
outcomes.
AB - OBJECTIVE: To compare patient and burn characteristics between patients who had a
pre-existing psychiatric diagnosis and patients who did not in a Burn Unit at an
academic hospital. BACKGROUND: Psychosocial issues are common in patients
recovering from a burn; however, little is known regarding hospital course and
discharge outcomes in patients with a pre-existing psychiatric diagnosis
presenting with a burn. Baseline medical comorbidities of burn patients have been
shown to be a significant risk for in-hospital mortality. METHODS: A
retrospective chart review of 479 consecutive patients admitted to the Burn Unit
of an academic hospital in Halifax, Nova Scotia between March 2nd 1995 and June
1st 2013 was performed. Extensive data regarding patient and burn characteristics
and outcomes was collected. Patients with and without pre-existing psychiatric
diagnoses at the time of hospital admission were compared. RESULTS: Sixty-three
(13%) patients had a psychiatric diagnosis, with the most common being depression
(52%). Forty-percent (n=25/63) of these patients had multiple pre-existing
psychiatric diagnoses. Patients with a psychiatric diagnosis had a greater total
body-surface-area (TBSA)% covered by a third-degree burn (p=0.001), and were more
likely to have an inhalation injury (p<0.001). These patients were also
significantly more likely to experience 6 of the 10 most prevalent in-hospital
complications and had a higher mortality rate (p=0.02). They were less likely to
be discharged home (p=0.001), and more likely to go to a home hospital (p=0.04)
or rehabilitation facility (p=0.03). Psychiatric diagnosis was associated with
significantly more placement issues (e.g. rehab bed unavailability, homeless)
upon discharge from the Burn Unit (p=0.01). The risk of death in burn patients
with pre-existing psychiatric disorders was about three times the risk of death
in patients with no psychiatric disorders when adjusting for other potential
confounders (95% CI, 1.13-9.10; p-value 0.03). CONCLUSION: Presence of a pre
existing psychiatric disorder in the burn patient was associated with worse
outcomes and was a significant predictor of death. Psychiatric diagnoses should
be identified early in burn treatment and efforts should be made to ensure a
comprehensive approach to inpatient support and patient discharge to reduce
unfavorable burn outcomes and placement issues.
PMID- 28412133
TI - The Southwest UK Burns Network (SWUK) experience of electronic cigarette
explosions and review of literature.
AB - INTRODUCTION: Since the introduction of e-cigarettes to the UK market in 2007
their popularity amongst young adults has significantly increased. These lithium
ion powered devices remain unregulated by the Standards Agency and as a result
burns centres across the world have seen an increasing number of patients
presenting with significant burns, resulting from poor quality batteries that
appear to be liable to explode when over-heated, over-charged or incorrectly
stored. METHODS: Retrospective and perspective review of all e-cigarette related
burns presenting to the Southwest Burns Network; South Wales Burns Centre
(Morriston Hospital) or to Bristol burns centre (Southmead Hospital) between Oct
15-July 16, followed by a review of available literature performed and eligible
papers identified using PRISMA 2009 Checklist. RESULTS: South Wales Burns Centre
(Morriston Hospital) (N=5), Bristol burns centre (Southmead Hospital) (N=7). 92%
of injuries were seen in male patients with a mean age of 34.58 (+/-12.7). The
mean TSBA sustained 2.54% of mixed depth, most common anatomical area is the
thigh 83% (n=10) with a mean 23.1(+/-5) days to heal with conservative
management. The literature search yielded 3 case series (Colaianni et al., 2016;
Kumetz et al., 2016; Nicoll et al., 2016) [8,9,12] and 4 case reports (Jablow and
Sexton, 2015; Harrison and Hicklin, 2016; Walsh et al., 2016; Shastry and
Langdorf, 2016) [6,7,10,11]. We compare our findings with the published studies.
CONCLUSION: The import and sale of e-cigarettes remains unrestricted. This
increases the risk of devices being available in the UK market that do not meet
the British Standard Specification, potentially increasing their risk of causing
fire and exploding. Consumers should be made aware of this risk, and advised of
adequate charging and storage procedures. In case lithium ion compounds leak
following a breach in the battery, first aid with mineral oil use is advocated to
avoid a further chemical reaction.
PMID- 28412134
TI - Clinical courses of herpes simplex virus-induced urethritis in men.
AB - We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced
non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a
clinic in Sendai, Japan, between April 2013 and December 2015. All the men
complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear
cells were observed in the urethral smears from 9 men. The 13 men were treated
with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens
became negative for HSV in 8 of the 10 men who returned to the clinic after
antibacterial treatment, and urethritis symptoms were alleviated. However,
herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them
were still positive for HSV in their FVU. HSV could be a cause of acute
urethritis without causing visible herpetic lesions. The shedding of HSV from the
urethra would spontaneously cease with alleviation of urethritis symptoms in most
cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions
could be developed in some cases. Early antiviral therapy is beneficial for
patients with HSV infections. The development of meatitis and the mononuclear
cell response in the urethral smear could be helpful to diagnose HSV-induced NGU.
Therefore, we should presumptively initiate anti-HSV therapy for patients with
signs and symptoms suggestive of HSV-induced NGU at their first presentation.
PMID- 28412135
TI - Moving beyond quality control in diagnostic radiology and the role of the
clinically qualified medical physicist.
AB - Quality control (QC), according to ISO definitions, represents the most basic
level of quality. It is considered to be the snapshot of the performance or the
characteristics of a product or service, in order to verify that it complies with
the requirements. Although it is usually believed that "the role of medical
physicists in Diagnostic Radiology is QC", this, not only limits the contribution
of medical physicists, but is also no longer adequate to meet the needs of
Diagnostic Radiology in terms of Quality. In order to assure quality practices
more organized activities and efforts are required in the modern era of
diagnostic radiology. The complete system of QC is just one element of a
comprehensive quality assurance (QA) program that aims at ensuring that the
requirements of quality of a product or service will consistently be fulfilled. A
comprehensive Quality system, starts even before the procurement of any
equipment, as the need analysis and the development of specifications are
important components under the QA framework. Further expanding this framework of
QA, a comprehensive Quality Management System can provide additional benefits to
a Diagnostic Radiology service. Harmonized policies and procedures and elements
such as mission statement or job descriptions can provide clarity and consistency
in the services provided, enhancing the outcome and representing a solid platform
for quality improvement. The International Atomic Energy Agency (IAEA) promotes
this comprehensive quality approach in diagnostic imaging and especially supports
the field of comprehensive clinical audits as a tool for quality improvement.
PMID- 28412136
TI - Dose painting by means of Monte Carlo treatment planning at the voxel level.
AB - PURPOSE: To develop a new optimization algorithm to carry out true dose painting
by numbers (DPBN) planning based on full Monte Carlo (MC) calculation. METHODS:
Four configurations with different clustering of the voxel values from PET data
were proposed. An optimization method at the voxel level under Lineal Programming
(LP) formulation was used for an inverse planning and implemented in CARMEN, an
in-house Monte Carlo treatment planning system. RESULTS: Beamlet solutions
fulfilled the objectives and did not show significant differences between the
different configurations. More differences were observed between the segment
solutions. The plan for the dose prescription map without clustering was the
better solution. CONCLUSIONS: LP optimization at voxel level without dose-volume
restrictions can carry out true DPBN planning with the MC accuracy.
PMID- 28412137
TI - Are Markers of Systemic Inflammation Good Prognostic Indicators in Colorectal
Cancer?
AB - Systemic inflammation has been proved to play a crucial role in promoting cancer
progression and metastasis in many cancer types, including colorectal cancer
(CRC). The aim of the present review was to provide an overview of studies
regarding the prognostic value of inflammation-based markers in patients with
CRC. A literature search was performed for articles reporting the prognostic
value of the Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-to
lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to
monocyte ratio (LMR) in relation to CRC outcomes. In resectable early-stage CRC,
high GPS scores seem significantly associated with cancer-specific survival. It
has also been suggested that adjuvant chemotherapy for stage II CRC could improve
cancer-specific survival in patients with high GPS scores. In patients with both
resectable and unresectable metastatic CRC and a higher GPS score, all studies
suggested poorer overall survival. In early-stage and resectable metastatic CRC,
the NLR seemed related to overall survival; however, the data for disease-free
survival were discordant. In metastatic disease, a possible correlation between a
greater NLR and poorer response to bevacizumab has been suggested. Data
concerning the prognostic and predictive role of the PLR and LMR in CRC are to
date insufficient. In patients with unresectable metastatic disease, inflammation
markers can be used to predict the chemotherapeutic outcome and monitor tumor
progression. However, further prospective studies might lead to better risk
stratification for patients eligible for curative surgery, thus, allowing the
restriction of neoadjuvant and adjuvant therapy to patients with high-risk CRC.
PMID- 28412138
TI - Early Postoperative FDG-PET-CT Imaging Results in a Relevant Upstaging in the pN2
Subgroup of Stage III Colorectal Cancer Patients.
AB - INTRODUCTION: Clinical practice guidelines regarding follow-up in patients after
curative resection of colorectal cancer (CRC) vary widely. Current follow-up
recommendations do not include additional postoperative imaging before starting
adjuvant treatment in any patients. We evaluated the potential benefit of our
institutional approach, recommending 18fluor-deoxy-glucose (FDG)-positron
emission tomography (PET)-computed tomography (CT) imaging in CRC stage III
patients with >=4 locoregional lymph node metastases (pN2). PATIENTS AND METHODS:
Our study included all patients from a single center with complete resection of a
pT1-4, pN2, cM0 CRC. All patients were considered free of distant metastases on
the basis of preoperative CT imaging of the chest, abdomen, and pelvis. The main
objective of the present study was to assess the proportion of patients with
changes of therapeutic management (defined as any other treatment than the
preplanned adjuvant chemotherapy) because of the results of additional
postoperative FDG-PET-CT imaging. RESULTS: Fifty patients (22 female/28 male)
were included; the median age was 64 years (range, 37-78 years). Previously
undiagnosed metastatic disease resulting in a change of the therapeutic
management was detected using postoperative FDG-PET-CT imaging in 7 patients
(14.0%; 95% confidence interval, 5.8%-26.7%). The number needed to screen to
detect new or previously occult metastases was 7 (7 of 50). CONCLUSION: To our
knowledge, this is the first study to evaluate the role of an additional
postoperative FDG-PET-CT scan before adjuvant treatment in patients with
completely resected CRC with >=4 lymph node metastases (pT1-4, pN2) and without
distant metastases on preoperative CT imaging (cM0). Postoperative FDG-PET-CT
imaging represents a valuable tool for the detection of new macrometastases in
the subgroup of pN2 cM0 CRC patients. The low number needed to screen for
consequent therapeutic changes is clinically relevant and should be further
evaluated.
PMID- 28412139
TI - Comparative Effectiveness Research: The Impact of Biologic Agents in Ethnic
Minorities With Metastatic Colorectal Cancer.
AB - BACKGROUND: Biologic agents have improved the outcomes of patients with
metastatic colorectal cancer (mCRC). However, the clinical trials included a
predominately white population (85%), with Hispanic and black patients
underrepresented. Thus, the real world benefit for the latter remains unknown.
Comparative effectiveness research is a tool allowing for this exploration.
PATIENTS AND METHODS: The demographic and clinical characteristics of patients
treated for mCRC from 2000 to 2011 were extracted from the medical records of
Montefiore Medical Center. A semiparametric accelerated failure time model was
used to assess the survival differences between patients receiving chemotherapy
(CT) alone versus CT plus biologic agents (CBT). RESULTS: Of the 290 patients
(black, 45.9%; Hispanic, 26.2%; and white, 27.9%), 53.8% received biologic
agents. The median overall survival was 15.2 months in the CT-alone group and
25.6 months in CBT group (P = .004). On univariate analysis, a lower number of
metastatic sites, carcinoembryonic antigen < 41 ng/mL, and more lines of CT were
associated with improved overall survival. In a propensity score-based analysis
of the entire cohort, CBT offered a survival benefit compared with CT alone
(increased median survival, 1.44-fold; 95% confidence interval [CI], 1.11-1.86; P
= .038). The results of the subgroup analysis suggested a survival benefit for
white patients (2.01; 95% CI, 1.26-3.23; P = .031) but not for Hispanic (1.42;
95% CI, 0.91-2.20; P = .370) or black (1.12; 95% CI, 0.76-1.66; P = .596)
patients. CONCLUSION: In the present cohort, CBT was associated with longer
survival, with the effect mainly driven by the outcomes for white patients, with
black patients not appearing to benefit. These data are provocative and warrant
further confirmation. Efforts to increase ethnic minority patients' enrollment in
clinical trials is required to prospectively define the benefit from novel
therapies.
PMID- 28412140
TI - Chronic sleep restriction promotes brain inflammation and synapse loss, and
potentiates memory impairment induced by amyloid-beta oligomers in mice.
AB - It is increasingly recognized that sleep disturbances and Alzheimer's disease
(AD) share a bidirectional relationship. AD patients exhibit sleep problems and
alterations in the regulation of circadian rhythms; conversely, poor quality of
sleep increases the risk of development of AD. The aim of the current study was
to determine whether chronic sleep restriction potentiates the brain impact of
amyloid-beta oligomers (AbetaOs), toxins that build up in AD brains and are
thought to underlie synapse damage and memory impairment. We further investigated
whether alterations in levels of pro-inflammatory mediators could play a role in
memory impairment in sleep-restricted mice. We found that a single
intracerebroventricular (i.c.v.) infusion of AbetaOs disturbed sleep pattern in
mice. Conversely, chronically sleep-restricted mice exhibited higher brain
expression of pro-inflammatory mediators, reductions in levels of pre- and post
synaptic marker proteins, and exhibited increased susceptibility to the impact of
i.c.v. infusion of a sub-toxic dose of AbetaOs (1pmol) on performance in the
novel object recognition memory task. Sleep-restricted mice further exhibited an
increase in brain TNF-alpha levels in response to AbetaOs. Interestingly, memory
impairment in sleep-restricted AbetaO-infused mice was prevented by treatment
with the TNF-alpha neutralizing monoclonal antibody, infliximab. Results
substantiate the notion of a dual relationship between sleep and AD, whereby
AbetaOs disrupt sleep/wake patterns and chronic sleep restriction increases brain
vulnerability to AbetaOs, and point to a key role of brain inflammation in
increased susceptibility to AbetaOs in sleep-restricted mice.
PMID- 28412141
TI - Toll like receptor 4 activation can be either detrimental or beneficial following
mild repetitive traumatic brain injury depending on timing of activation.
AB - A history of repeated concussion has been linked to the later development of
neurodegeneration, which is associated with the accumulation of
hyperphosphorylated tau and the development of behavioral deficits. However, the
role that exogenous factors, such as immune activation, may play in the
development of neurodegeneration following repeated mild traumatic brain injury
(rmTBI) has not yet been explored. To investigate, male Sprague-Dawley rats were
administered three mTBIs 5days apart using the diffuse impact-acceleration model
to generate ~100G. Sham animals underwent surgery only. At 1 or 5days following
the last injury rats were given the TLR4 agonist, lipopolysaccharide (LPS,
0.1mg/kg), or saline. TLR4 activation had differential effects following rmTBI
depending on the timing of activation. When given at 1day post-injury, LPS
acutely activated microglia, but decreased production of pro-inflammatory
cytokines like IL-6. This was associated with a reduction in neuronal injury,
both acutely, with a restoration of levels of myelin basic protein (MBP), and
chronically, preventing a loss of both MBP and PSD-95. Furthermore, these animals
did not develop behavioral deficits with no changes in locomotion, anxiety,
depressive-like behavior or cognition at 3months post-injury. Conversely, when
LPS was given at 5days post-injury, it was associated acutely with an increase in
pro-inflammatory cytokine production, with an exacerbation of neuronal damage and
increased levels of aggregated and phosphorylated tau. At 3months post-injury,
there was a slight exacerbation of functional deficits, particularly in cognition
and depressive-like behavior. This highlights the complexity of the immune
response following rmTBI and the need to understand how a history of rmTBI
interacts with environmental factors to influence the potential to develop later
neurodegeneration.
PMID- 28412142
TI - Early enriched physical environment reverses impairments of the hippocampus, but
not medial prefrontal cortex, of socially-isolated mice.
AB - Early social isolation (SI) produces a variety of emotional, behavioral and
cognitive abnormalities. Conversely, environmental enrichment (EE), a complicated
social and physical construct, offers beneficial effects on brain plasticity and
development. However, whether or not exclusive physical EE is sufficient to
reverse the adverse consequences of early SI remains unclear. Here we reported
that 1month-old solitary mice housed in the EE for 8weeks corrected spatial
cognitive dysfunction, but did not ameliorate social interaction deficits and
increased anxiety-like behavior. Pathological analyses revealed that the enriched
environment decreased cellular apoptosis, synaptic protein loss, myelination
defect and microglial activation in the hippocampus, but not medial prefrontal
cortex (mPFC) of mice housed singly. Moreover, increased nuclear factor-kappaB
and interleukin-1beta levels, and downregulation of brain-derived neurotrophic
factor signaling pathway were normalized in the hippocampus rather than mPFC of
these animals. Our results revealed a brain region-specific effectiveness of
physical EE in remediating brain impairment of adolescent SI mice, with a
complete reversal of hippocampus-dependent cognitive dysfunctions, but without
mitigation of mPFC associated anxiety and social interaction defects. This
finding emphasizes the irreplaceable role of social life for the early brain
development.
PMID- 28412143
TI - Thermo-sensitive assembly of the biomaterial REP reduces hematoma volume
following collagenase-induced intracerebral hemorrhage in rats.
AB - Intracerebral hemorrhage (ICH) frequently results in severe disabilities and high
mortality. RGD-containing elastin-like polypeptide (REP), a modified elastin-like
polypeptide (ELP), is a thermally responsive biopolymer. REP has high affinity
for cells and is known to show non-immunotoxicity, -cytotoxicity, and
inflammatory responses. Here we found that administration of REP in the acute
phase of the ICH rat model reduced the hematoma volume, decreased the number of
activated microglia, attenuated the expression of von Willebrand Factor (vWF),
and prevented the leakage of immunoglobulin G (IgG) into the cerebral parenchyma
without any occlusion of intact microvessels. Therefore, the present data suggest
that REP treatment could be a novel therapeutic strategy for attenuating the
acute phase of ICH.
PMID- 28412144
TI - Quantitative microscopy-based measurements of circulating nanoparticle
concentration using microliter blood volumes.
AB - Nanoparticles (NPs) are potential drug delivery vehicles for treatment of a broad
range of diseases. Intravenous (IV) administration, the most common form of
delivery, is relatively non-invasive and provides (in theory) access throughout
the circulatory system. However, in practice, many IV injected NPs are quickly
eliminated by specialized phagocytes in the liver and spleen. Consequently, new
materials have been developed with the capacity to significantly extend the
circulating half-life of IV administered NPs. Unfortunately, current procedures
for measuring circulation half-lives are often expensive, time consuming, and can
require large blood volumes that are not compatible with mouse models of disease.
Here we describe a simple and reliable procedure for measuring circulation half
life utilizing quantitative microscopy. This method requires only 2MUL of blood
and minimal sample preparation, yet provides robust quantitative results.
PMID- 28412145
TI - Role of flexible bronchoscopy in non-resolving community-acquired pneumonia - A
retrospective analysis.
PMID- 28412146
TI - Acetate-detoxification of wood hydrolysates with alkali tolerant Bacillus sp. as
a strategy to enhance the lipid production from Rhodosporidium toruloides.
AB - The aim of the current work was to convert an acetate-rich hemicellulose liquid
fraction (LF) from hot-water extraction of Betula pendula to oils for biodiesel,
with Rhodosporidium toruloides. The toxicity of acetate was circumvented by
biological detoxification with an isolated alkali-tolerant and acetate-resistant
Bacillus sp. strain. Removal of other lignocellulose-derived inhibitors, such as
furfural and phenols, was evaluated by two strategies; an activated carbon (AC)
treatment of the undiluted LF, and dilution of the LF by 25% (0.75LF) and 50%.
(0.50LF). The bacterium consumed most of the acetic acid in 6-8days in the
treated or diluted media, which were subsequently used for cultivation of the
yeast, for conversion of sugars to oils. The oil concentration reached 2.8 and
1.8g/L, in the AC LF and 0.75LF medium, respectively. In comparison, the oil
accumulation in the same media without prior cultivation of Bacillus sp. was 0.86
and 0.03g/L, respectively.
PMID- 28412147
TI - Anaerobic co-digestion of microalgal biomass and wheat straw with and without
thermo-alkaline pretreatment.
AB - This study aimed at analyzing the anaerobic co-digestion of microalgal biomass
grown in wastewater and wheat straw. To this end, Biochemical Methane Potential
(BMP) tests were carried out testing different substrate proportions (20-80, 50
50 and 80-20%, on a volatile solid basis). In order to improve their
biodegradability, the co-digestion of both substrates was also evaluated after
applying a thermo-alkaline pretreatment (10% CaO at 75 degrees C for 24h). The
highest synergies in degradation rates were observed by adding at least 50% of
wheat straw. Therefore, the co-digestion of 50% microalgae - 50% wheat straw was
investigated in mesophilic lab-scale reactors. The results showed that the
methane yield was increased by 77% with the co-digestion as compared to
microalgae mono-digestion, while the pretreatment only increased the methane
yield by 15% compared to the untreated mixture. Thus, the anaerobic co-digestion
of microalgae and wheat straw was successful even without applying a thermo
alkaline pretreatment.
PMID- 28412148
TI - No evidence to support a role for Helicobacter pylori infection and plasminogen
binding protein in autoimmune pancreatitis and IgG4-related disease in a UK
cohort.
AB - BACKGROUND AND OBJECTIVES: Helicobacter pylori (H.pylori) plasminogen binding
protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis
(AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We
investigated exposure to H. pylori infection, cytokine response and immunological
memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS:
Clinical and endoscopic evidence of peptic ulceration, serological H. pylori
exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52
disease controls (DC) with autoimmune or inflammatory conditions with an elevated
serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and
immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were
used to detect immune responses to H. pylori PBP. RESULTS: 85% of IgG4-RD
patients had pancreatic and/or biliary disease, 89% had extra-pancreatic
manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%),
gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in
IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic
inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1
4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54)
compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B
cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS:
In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H.
pylori, cytokine response and immunological memory to H. pylori PBP did not
differ in IgG4-RD patients compared with DC. This study does not support a role
for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT:
Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.
PMID- 28412149
TI - Prevalence of arrhythmias in patients with type 2 diabetes and the role of
structural changes in myocardium in their development.
AB - OBJECTIVE: The aim of the study was to evaluate the prevalence of arrhythmias in
patients with type 2 diabetes and their relationships with the structural
parameters of the heart. METHODS: A retrospective case-control study was
conducted using clinical and biochemical profiles of patients with diabetes at
the Endocrinology Centre and City Clinical Hospital No. 40, Ekaterinburg, Russia.
RESULTS: The total study sample included 75 subjects. The average age (SD) was
48.2 (5.6) years, and the mean duration of diabetes (SD) was 6.2 (2.4) years. The
most common type of extrasystoles were the single supraventricular extrasystoles,
observed in 72.29% of cases (vs 38.89% in the control group) and paired
supraventricular extrasystoles, which were identified in 30% of cases (vs 19.44%
in the control group). Ventricular cardiac arrhythmias in the form of ventricular
extrasystoles (VE) were identified in 25.71% of cases (13.89% in the control
group). CONCLUSIONS: This study revealed the signs of the morphological
restructuring of the right chambers of the heart and a relatively high prevalence
of supraventricular arrhythmias in the early stages of type 2 diabetes. Moreover,
according to the results, the incidence of some types of supraventricular
arrhythmias and the occurrence of tachycardia episodes in patients with type 2
diabetes mostly depends on the restructuring of the right chambers of the heart,
which may be caused by the peculiarities of the cardiac innervation, with the
higher density of choline and adrenergic plexuses in the right chambers.
PMID- 28412150
TI - Epidemiological features of and changes in incidence of infectious diseases in
China in the first decade after the SARS outbreak: an observational trend study.
AB - BACKGROUND: The model of infectious disease prevention and control changed
significantly in China after the outbreak in 2003 of severe acute respiratory
syndrome (SARS), but trends and epidemiological features of infectious diseases
are rarely studied. In this study, we aimed to assess specific incidence and
mortality trends of 45 notifiable infectious diseases from 2004 to 2013 in China
and to investigate the overall effectiveness of current prevention and control
strategies. METHODS: Incidence and mortality data for 45 notifiable infectious
diseases were extracted from a WChinese public health science data centre from
2004 to 2013, which covers 31 provinces in mainland China. We estimated the
annual percentage change in incidence of each infectious disease using joinpoint
regression. FINDINGS: Between January, 2004, and December, 2013, 54 984 661 cases
of 45 infectious diseases were reported (average yearly incidence 417.98 per 100
000). The infectious diseases with the highest yearly incidence were hand, foot,
and mouth disease (114.48 per 100 000), hepatitis B (81.57 per 100 000), and
tuberculosis (80.33 per 100 000). 132 681 deaths were reported among the 54 984
661 cases (average yearly mortality 1.01 deaths per 100 000; average case
fatality 2.4 per 1000). Overall yearly incidence of infectious disease was higher
among males than females and was highest among children younger than 10 years.
Overall yearly mortality was higher among males than females older than 20 years
and highest among individuals older than 80 years. Average yearly incidence rose
from 300.54 per 100 000 in 2004 to 483.63 per 100 000 in 2013 (annual percentage
change 5.9%); hydatid disease (echinococcosis), hepatitis C, and syphilis showed
the fastest growth. The overall increasing trend changed after 2009, and the
annual percentage change in incidence of infectious disease in 2009-13 (2.3%) was
significantly lower than in 2004-08 (6.2%). INTERPRETATION: Although the overall
incidence of infectious diseases was increasing from 2004, the rate levelled off
after 2009. Effective prevention and control strategies are needed for diseases
with the highest incidence-including hand, foot, and mouth disease, hepatitis B,
and tuberculosis-and those with the fastest rates of increase (including hydatid
disease, hepatitis C, and syphilis). FUNDING: Chinese Ministry of Science and
Technology, National Natural Science Foundation (China).
PMID- 28412151
TI - Infectious diseases in China in the post-SARS era.
PMID- 28412152
TI - Discrepancies between home medication and patient documentation in primary care.
AB - BACKGROUND: Medication Reconciliation leads to quick detection of drug-related
problems, studies in ambulatory care are scarce. The recently introduced
Medication Plan in Germany serves as an ideal basis for Medication
Reconciliation. OBJECTIVE: The study aim was to provide accurate data on the
magnitude of discrepancy between the prescription and the actually taken
medicine. Clinical relevance of discrepancies was assessed to estimate the impact
on medication safety. METHODS: Patients were assessed at home, data was
reconciled with the physician's documentation. Discrepancies were analyzed and
stratified. Risk for hospitalization, risk for falls and the potential for drug
drug interactions was estimated based on literature. Drugs were tested for its
origin and grouped to indication clusters. Detected DRPs at a Medication Review
were linked to the results at Medication Reconciliation. RESULTS: Medication of
142 elderly patients from 12 practices was reconciled. 1498 drugs were found at
the home assessment, 1099 (73.4%) of which were detected in the physician's
documentation. 94.4% of the patients were affected by discrepancies. A total of
2.8 +/- 2.4 drugs was undocumented per patient. 26.6% of missing drugs were
prescribed by medical specialists, 42.5% of drugs of unknown origin were
prescription drugs. 53.9% of the patients used a undocumented drug, which carried
a high risk for hospitalization. 23.1% of the drugs not covered were used for
treatment of cardiovascular diseases. 65.8% of the differing drugs caused at
least one DRP. CONCLUSION: A high discrepancy between the drugs used by the
patient and the medication documented by the primary care physician could be
found. Relating drugs had a profound systemic effect and were particular relevant
to medication safety. Many drugs were prescription drugs. The majority of
differing drugs caused DRPs. A collaborative Medication Reconciliation as part of
a Medication Management could compile the entire medication and increase patient
safety.
PMID- 28412153
TI - The effect of counseling on willingness to use a hypothetical medication and
perceptions of medication safety.
AB - BACKGROUND: Poor medication adherence is an ongoing issue, and contributes to
increased hospitalizations and healthcare costs. Although most adverse effects
are rare, the perceived risk of adverse effects may contribute to low adherence
rates. OBJECTIVES: The objective of this study was to determine how adverse
effect likelihood and pharmacist counseling on adverse effect prevention affects
individuals': (1) willingness to use a hypothetical medication and (2)
perceptions of medication safety. METHODS: This study used a 3 * 3 experimental
design. Participants (n = 601) viewed a hypothetical scenario asking them to
imagine being prescribed an anti-asthma medication that could cause fungal
infections of the throat. Participants were randomized to 1 of 9 scenarios that
differed on: probability of developing an infection (5%, 20%, no probability
mentioned) and whether they were told how to reduce the risk of infection (no
prevention strategy discussed, prevention strategy discussed, prevention strategy
discussed with explanation for how it works). Participants were recruited through
Amazon Mechanical Turk. RESULTS: Participants were less willing to take the
medication (F = 12.86, p < 0.0001) and considered it less safe (F = 13.11, p <
0.0001) when the probability of fungal infection was presented as 20% compared to
5% or when no probability information was given. Participants were more willing
to take the medication (F = 11.78, p < 0.0001) and considered it safer (F =
11.17, p < 0.0001) when a prevention strategy was given. Finally, there was a non
statistically significant interaction between the probability and prevention
strategy information such that provision of prevention information reduced the
effect of variation in the probability of infection on both willingness to use
the medication and perceived medication safety. CONCLUSIONS: Optimal risk
communication involves more than informing patients about possible adverse
effects. Pharmacists could potentially improve patient acceptance of therapeutic
recommendations, and allay medication safety concerns, by counseling about
strategies patients can implement to reduce the perceived risk of adverse
effects.
PMID- 28412154
TI - Quality Indicator for Epilepsy Treatment 15 (QUIET-15): Intervening after
recurrent seizures in the elderly.
AB - In this study, we examined the provision of care to older adults with epilepsy
and compliance with the "Quality Indicator for Epilepsy Treatment 15" (QUIET-15)
measure. We analyzed 2008-2010, 5% random sample of Medicare beneficiaries
augmented with data from all beneficiaries who identified as a minority with
claims related to seizures (780.3x) or epilepsy (345.xx). Of 36,912 identified
epilepsy cases, 12.6% had >=1 emergency room (ER) visit for seizure(s). For those
who presented to ER, among those taking anti-epileptic drugs (AEDs), AED was
changed in 15.4%, dose adjusted in 19.7%, and stopped in 14.9%; among those not
taking AED, therapy was initiated in 68.5%. In adjusted logistic regressions,
African-Americans were more likely to have recurrent seizures than Whites (OR
1.41, 95%CI 1.27-1.56), while Asians were less likely to have recurrent seizures
(OR 0.71, 95%CI 0.57-0.89). There were no significant racial/ethnic differences
in the likelihood of a post-seizure intervention. The chance of seizure
recurrence leading to ER visit decreased with age and increased with the number
of comorbidities. Patients with seizure recurrence were more likely to be taking
an enzyme-inducing AED (OR 1.69, 95%CI 1.57-1.82) and receiving Part D Low Income
Subsidy (OR 1.36, 95%CI 1.22-1.51). The probability of AED change after a seizure
was higher for patients with >=4 comorbidities (OR 1.69, 95%CI 1.25-2.27),
patients who saw a neurologist (OR 1.49, 95%CI 1.30-1.70), and patients who were
taking an enzyme-inducing AED (OR 1.47, 95%CI 1.27-1.71). Overall, a minority of
Medicare beneficiaries experienced seizure recurrence that resulted in an ER
visit. However, only half of them received treatment concordant with QUIET-15.
Though racial differences were observed in occurrence of seizures, none were
noted in the provision of care.
PMID- 28412155
TI - Ascorbic acid inhibits human insulin aggregation and protects against amyloid
induced cytotoxicity.
AB - Protein aggregation into oligomers and fibrils are associated with many human
pathophysiologies. Compounds that modulate protein aggregation and interact with
preformed fibrils and convert them to less toxic species, expect to serve as
promising drug candidates and aid to the drug development efforts against
aggregation diseases. In present study, the kinetics of amyloid fibril formation
by human insulin (HI) and the anti-amyloidogenic activity of ascorbic acid (AA)
were investigated by employing various spectroscopic, imaging and computational
approaches. We demonstrate that ascorbic acid significantly inhibits the
fibrillation of HI in a dose-dependent manner. Interestingly ascorbic acid
destabilise the preformed amyloid fibrils and protects human neuroblastoma cell
line (SH- SY5Y) against amyloid induced cytotoxicity. The present data signifies
the role of ascorbic acid that can serve as potential molecule in preventing
human insulin aggregation and associated pathophysiologies.
PMID- 28412156
TI - Tyrosine oxidation and nitration in transmembrane peptides is connected to lipid
peroxidation.
AB - Tyrosine nitration is an oxidative post-translational modification that can occur
in proteins associated to hydrophobic bio-structures such as membranes and
lipoproteins. In this work, we have studied tyrosine nitration in membranes using
a model system consisting of phosphatidylcholine liposomes with pre-incorporated
tyrosine-containing 23 amino acid transmembrane peptides. Tyrosine residues were
located at positions 4, 8 or 12 of the amino terminal, resulting in different
depths in the bilayer. Tyrosine nitration was accomplished by exposure to
peroxynitrite and a peroxyl radical donor or hemin in the presence of nitrite. In
egg yolk phosphatidylcholine liposomes, nitration was highest for the peptide
with tyrosine at position 8 and dramatically increased as a function of oxygen
levels. Molecular dynamics studies support that the proximity of the tyrosine
phenolic ring to the linoleic acid peroxyl radicals contributes to the efficiency
of tyrosine oxidation. In turn, alpha-tocopherol inhibited both lipid
peroxidation and tyrosine nitration. The mechanism of tyrosine nitration involves
a "connecting reaction" by which lipid peroxyl radicals oxidize tyrosine to
tyrosyl radical and was fully recapitulated by computer-assisted kinetic
simulations. Altogether, this work underscores unique characteristics of the
tyrosine oxidation and nitration process in lipid-rich milieu that is fueled via
the lipid peroxidation process.
PMID- 28412157
TI - Are we ready for a "tissue identity card" of inherited cardiomyopathies?
PMID- 28412160
TI - Study design for vulnerable older adults with multiple myeloma.
PMID- 28412159
TI - Synthesis and evaluation of a series of pyridine and pyrimidine derivatives as
type II c-Met inhibitors.
AB - In this study, a series of novel pyridine and pyrimidine-containing derivatives
were designed, synthesized and biologically evaluated for their c-Met inhibitory
activities. In the biological evaluation, half of the target compounds exhibited
moderate to potent c-Met inhibitory activities. Among which, it is noteworthy
that compounds 13d not only showed most potent c-Met inhibitory potency but also
displayed excellent anti-proliferative activity (IC50=127nM against EBC-1 cell
line) as well as an acceptable kinase selectivity profile. Moreover, the western
blot assay indicated that 13d inhibited c-Met phosphorylation in EBC-1 cells in a
dose-dependent manner, with complete abolishment at 0.1mM. All these experimental
results suggested that 13d could be served as a promising lead compound for the
development of anticancer agents.
PMID- 28412158
TI - Lidocaine attenuation testing: An in vivo investigation of putative LQT3
associated variants in the SCN5A-encoded sodium channel.
AB - BACKGROUND: Long QT syndrome type 3 (LQT3) accounts for 5%-10% of long QT
syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium
channel. Approximately 2% of healthy individuals host rare SCN5A variants of
uncertain significance (VUS). Distinction of true LQT3-causative mutations from
background genetic noise is essential. OBJECTIVE: The purpose of this study was
to assess the use of the lidocaine attenuation test (LAT) in evaluating patients
with possible LQT3. METHODS: We reviewed the LAT results and medical records for
25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a
loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion
at 50 MUg/(kg?min) for 20 minutes. If the corrected QT interval shortened by >=30
ms, the LAT was defined as positive. RESULTS: Sixteen patients (64%) had a
positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT
correlated in 86% of cases with abnormal in vitro channel function (mean
corrected QT interval attenuation 43 +/- 3 ms vs 25 +/- 5 ms for wild-type
variants; P = .03). Four of 5 patients (80%) with a VUS had a positive LAT
(T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated
abnormal in vitro function and a positive LAT, opening the door for a potential
variant promotion from VUS to likely pathogenic. CONCLUSION: The LAT may help
distinguish true LQT3-causative mutations from an otherwise noncontributory VUS.
Given that lidocaine acts as a late sodium current blocker, a positive LAT may
enable the early identification of a pathological accentuation of the late sodium
current that could be targeted therapeutically.
PMID- 28412161
TI - The effect of the apneic period on the respiratory physiology of patients
undergoing intubation in the ED.
AB - OBJECTIVES: We sought to examine the physiological impact the apneic period has
on the respiratory physiology of patients undergoing intubation in the emergency
department and whether DAO, the delivery of 15L oxygen by nasal cannula during
apnea, can affect the development of respiratory acidosis. METHODS: This was a
prospective observational cohort study conducted at an urban academic level 1
trauma center. A convenience sample of 100 patients was taken. Timed data
collection forms were completed during the periintubation period. We report the
mean ABG and end-tidal CO2 (EtCO2) values between those with normal and prolonged
apnea times (>60s) and between those who received DAO and those who did not.
RESULTS: 100 patients met our inclusion criteria. There were no significant
differences in the pre-RSI ABG values between those who received DAO and those
who did not and between those with apnea times less than or >60s. Only in the
group of patients with apnea times >60s did significant changes in respiratory
physiology occur. DAO did not alter the trend in respiratory acidosis during the
periintubation period. EtCO2 increased as apnea times were prolonged, and DAO
altered this trend. CONCLUSIONS: Post-RSI EtCO2 increased as apnea times were
prolonged. DAO may alter this trend. Statistically significant changes in pH and
PaCO2 (mean differences of 0.15 and 12.5, respectively) occurred in the group of
patients who had mean apnea times of >60s but not in those with apnea times <60s.
PMID- 28412162
TI - Incidence and clinical features of sacral insufficiency fracture in the emergency
department.
AB - INTRODUCTION: A sacral insufficiency fracture (SIF) often manifests as low back
pain or sciatica in the absence of any antecedent trauma. These fractures may be
missed because of lack of appropriate imaging. The purpose of this study was to
clarify the incidence and clinical features of SIF as well as the characteristic
findings on magnetic resonance imaging (MRI) of the lumbar spine. MATERIALS AND
METHODS: The study participants comprised 250 patients (132 male, 118 female;
mean age 58.6years) with pelvic trauma. SIF was identified on computed tomography
or MRI. The incidence, initial symptoms, and time delay between the first visit
and an accurate diagnosis of SIF were recorded. RESULTS: We detected 11 cases of
SIF. Initial symptoms of SIF were low back pain (36.4%), gluteal pain (63.6%),
and coxalgia (18.2%). Two patients complained of both low back pain and gluteal
pain. The mean delay between the first visit and an accurate diagnosis of SIF was
23.9days. This time interval was significantly longer than in patients with other
types of pelvic fracture. Four patients underwent MRI targeting the lumbar spine
to investigate their symptoms. In all 4 patients, the signal intensity on T1
weighted and fat-suppressed images of the second sacral segment was low and high,
respectively. CONCLUSION: This study demonstrates that accurate diagnosis of SIF
may be delayed because of difficulties in detecting this type of fracture on
plain X-ray and the non-specific nature of the presenting complaints. Emergency
physicians should keep SIF in mind when investigating patients who complain of
low back pain or gluteal pain. Findings at the second sacral segment on MRI
targeting the lumbar spine may aid early diagnosis of this type of pelvic
fracture.
PMID- 28412163
TI - Electroencephalographic responses of anaesthetized pigs (Sus scrofa) to tail
docking using clippers or cautery iron performed at 2 or 20 days of age.
AB - OBJECTIVE: To compare electroencephalographic (EEG) responses of pigs to tail
docking using clippers or cautery iron, performed at 2 or 20 days of age. STUDY
DESIGN: Prospective, randomised controlled experimental study. ANIMALS: A total
of 40 Large White x Landrace entire male pigs aged 2 (n=20) or 20 (n=20) days
were randomly assigned to undergo tail docking using clippers or cautery iron.
METHODS: Anaesthesia was induced and maintained with halothane delivered in
oxygen. Following instrumentation, end-tidal halothane concentration was
stabilised at 1.0+/-0.05%, and EEG recording commenced. After a 5 minute baseline
period, tail docking was performed and recording continued for additional 10
minutes. EEG data were subjected to Fast Fourier transformation, yielding the
summary variables median frequency (F50), 95% spectral edge frequency (F95) and
total power (PTOT). Variables recorded during the baseline period were compared
with those calculated at consecutive 15 second intervals following tail docking.
RESULTS: Following tail docking, F50 decreased briefly but significantly in 2-day
olds, whereas 20-day-olds exhibited a sustained increase in F50 (p<0.05).
Immediately after tail docking, F50 was overall lower in 2-day-olds than in 20
day-olds (p<0.05). F95 increased after docking in 20-day-olds docked using
clippers (p<0.05) but did not change in 20-day-olds docked using cautery iron or
in 2-day-olds docked using either method. Overall, F95 was lower in 2-day-olds
than in 20-day-olds from 30 to 60 seconds after docking (p<0.05). PTOT decreased
after docking in 20-day-olds (p<0.05) but did not change in 2-day-olds. Overall,
PTOT was lower in 2- than in 20-day-olds during baseline and after tail docking
(p<0.05). CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that tail
docking using clippers is more acutely painful than docking using cautery iron
and that docking within the first days of birth may be less acutely painful than
docking at a later age.
PMID- 28412164
TI - Diagnosis and Management of Oropharyngeal Dysphagia Among Older Persons, State of
the Art.
AB - Oropharyngeal dysphagia (OD) is a condition recognized by the World Health
Organization and defined as the difficulty or inability to move a bolus safely
and effectively from the oral cavity to the esophagus, and can include
aspirations, choking, and residue. OD is pandemic among different phenotypes of
older people, affecting between 27% and 91% of the population 70 years or older.
Although OD can be diagnosed by well-defined clinical methods and complementary
explorations, in the clinical setting OD is seldom systematically screened and
treated, and awareness among the medical/geriatric community is scarce. The
etiology of OD in this population includes many concomitant risk factors with
neurogenic and neurodegenerative processes, muscular weakness, and sarcopenia.
The pathophysiology includes mechanical deficits in the swallow response (mainly
delayed laryngeal vestibule closure time and weak tongue thrust), reduced
pharyngeal sensitivity, and sensory/motor central nervous system impairments.
Recently, OD has been recognized as a geriatric syndrome due to its high
prevalence and its relationship with many comorbidities and their poor outcomes,
including malnutrition, respiratory infections and aspiration pneumonia,
functional disability and frailty, institutionalization and increased
readmissions, and mortality. There is an evidence-based and effective treatment
for OD in the elderly mainly oriented to compensating swallow impairments through
adaptation of fluid viscosity and solid food textures to avoid aspiration and
choking, and improving nutritional status and oral health to avoid respiratory
infections. This has been defined as the minimal effective treatment to be
provided to this population. New treatments aiming at recovering the swallowing
function are under research with promising results, and the near future will
provide us with methods to stimulate the swallow response with pharmacological or
physical stimuli.
PMID- 28412165
TI - Effects of a Community-Based Program for Oral Health and Nutrition on Cost
Effectiveness by Preventing Disability in Japanese Frail Elderly: A Quasi
Experimental Study Using Propensity Score Matching.
AB - OBJECTIVE: In the Japanese Long-Term Care Insurance (LTCI) system, a community
based program for oral health and nutrition (OHN program) has been implemented
with the aim of reducing incident disability and care costs. However, the
effectiveness of this program has not been confirmed epidemiologically. The
purpose of the present study was to test the hypothesis that the OHN program does
reduce incident disability and care costs. DESIGN: A prospective study with a 28
month follow-up period was conducted using data from administrative databases at
Tagajo City, Japan. Among frail elderly persons (aged 65 years or more) who were
enrolled in the LTCI program in Tagajo, 64 participants in the OHN program and
128 controls (nonparticipants) were selected by propensity score matching.
MEASUREMENTS: We used 2 types of outcome measure: composite outcome (incident
disability and death) and care cost. Data on incident disability were retrieved
from the public LTCI database. Care cost was defined as the total amount of LTCI
service cost added to medical care cost. RESULTS: The hazard ratio of composite
outcome was significantly lower for the intervention group than for the control
group (hazard ratio = 0.32, 95% confidence interval 0.12-0.82). Even when we set
incident disability as an outcome, the hazard ratio for the intervention group
did not change (hazard ratio = 0.33, 95% confidence interval 0.11-0.97). The mean
cumulative care cost during the 28 months tended to be lower for the intervention
group ($4893) than that for the control group ($5770), but this was not
statistically significant by the gamma regression model (cost ratio = 0.85, P =
.513). The mean care cost per unit follow-up period (1 month) for the
intervention group was significantly lower (cost ratio = 0.54, P = .027).
CONCLUSIONS: The results of this study suggest that the OHN program is effective
for preventing incident disability and, consequently, for saving care costs per
unit survival period.
PMID- 28412166
TI - Palliative Care Development in European Care Homes and Nursing Homes: Application
of a Typology of Implementation.
AB - BACKGROUND: The provision of institutional long-term care for older people varies
across Europe reflecting different models of health care delivery. Care for dying
residents requires integration of palliative care into current care work, but
little is known internationally of the different ways in which palliative care is
being implemented in the care home setting. OBJECTIVES: To identify and classify,
using a new typology, the variety of different strategic, operational, and
organizational activities related to palliative care implementation in care homes
across Europe. DESIGN AND METHODS: We undertook a mapping exercise in 29 European
countries, using 2 methods of data collection: (1) a survey of country
informants, and (2) a review of data from publically available secondary data
sources and published research. Through a descriptive and thematic analysis of
the survey data, we identified factors that contribute to the development and
implementation of palliative care into care homes at different structural levels.
From these data, a typology of palliative care implementation for the care home
sector was developed and applied to the countries surveyed. RESULTS: We
identified 3 levels of palliative care implementation in care homes: macro
(national/regional policy, legislation, financial and regulatory drivers), meso
(implementation activities, such as education, tools/frameworks, service models,
and research), and micro (palliative care service delivery). This typology was
applied to data collected from 29 European countries and demonstrates the
diversity of palliative care implementation activity across Europe with respect
to the scope, type of development, and means of provision. We found that macro
and meso factors at 2 levels shape palliative care implementation and provision
in care homes at the micro organizational level. CONCLUSIONS: Implementation at
the meso and micro levels is supported by macro-level engagement, but can happen
with limited macro strategic drivers. Ensuring the delivery of consistent and
high-quality palliative care in care homes is supported by implementation
activity at these 3 levels. Understanding where each country is in terms of
activity at these 3 levels (macro, meso, and micro) will allow strategic focus on
future implementation work in each country.
PMID- 28412167
TI - Mortality in Nursing Homes Following Emergency Evacuation: A Systematic Review.
AB - OBJECTIVES: To determine the risk associated with mortality among nursing home
residents within 6 months following an evacuation because of man-made or natural
disasters. DESIGN: A systematic review conducted in accordance with the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement.
SETTING: All peer-reviewed studies published in English, French, German, or
Spanish between January 1, 2000 and December 31, 2015, examining mortality within
6 months of disaster evacuation from a nursing home. MEASUREMENTS: Extracted
information included study and population characteristics, mortality measures,
and risk factors. Studies were examined using the disaster management cycle that
considers preparedness, response, recovery, and mitigation. RESULTS: The 10
included studies were published between 2010 and 2015 with one-half conducted in
the United States. Only 3 studies detailed the preparedness stage, and 4 detailed
the response stage of the disaster management cycle. Mortality was measured as an
indicator of recovery and was found to be elevated at 1 month [from 0.03% (n =
1088) to 10.5% (n = 75)] 3 months [from 0.08% (n = 3091) to 15.2% (n = 197)], and
6 months [from 14.9% (n = 263) and 16.8% (n = 22)] postevacuation compared with
pre-evacuation and sheltering-in-place. Studies identified vulnerable residents
as being over 80 years of age, frail, dependent, male residents with multiple
comorbidities and, made recommendations on disaster preparedness. CONCLUSIONS:
There is little research on the effects of evacuation on nursing home residents,
which is surprising considering the elevated risk of mortality postevacuation.
Evacuation seems to have a negative effect on the survival of nursing home
residents independent of the effect of the disaster. Standard evacuation
procedures may be less applicable to this vulnerable population because of extra
challenges they face in disasters.
PMID- 28412168
TI - Facilitating Translational Nanomedicine via Predictive Safety Assessment.
AB - Extensive research on engineered nanomaterials (ENMs) has led to the development
of numerous nano-based formulations for theranostic purposes. Although some nano
based drug delivery systems already exist on the market, growing numbers of newly
designed ENMs exhibit improved physicochemical properties and are being assessed
in preclinical stages. While these ENMs are designed to improve the efficacy of
current nano-based therapeutic or imaging systems, it is necessary to thoroughly
determine their safety profiles for successful clinical applications. As such,
our aim in this mini-review is to discuss the current knowledge on predictive
safety and structure-activity relationship (SAR) analysis of major ENMs at the
developing stage, as well as the necessity of additional long-term toxicological
analysis that would help to facilitate their transition into clinical practices.
We focus on how the interaction of these nanomaterials with cells would trigger
signaling pathways as molecular initiating events that lead to adverse outcomes.
These mechanistic understandings would help to design safer ENMs with improved
therapeutic efficacy in clinical settings.
PMID- 28412169
TI - Engineered Exosomes as Vehicles for Biologically Active Proteins.
AB - Exosomes represent an attractive vehicle for the delivery of biomolecules.
However, mechanisms for loading functional molecules into exosomes are relatively
unexplored. Here we report the use of the evolutionarily conserved late-domain (L
domain) pathway as a mechanism for loading exogenous proteins into exosomes. We
demonstrate that labeling of a target protein, Cre recombinase, with a WW tag
leads to recognition by the L-domain-containing protein Ndfip1, resulting in
ubiquitination and loading into exosomes. Our results show that Ndfip1 expression
acts as a molecular switch for exosomal packaging of WW-Cre that can be
suppressed using the exosome inhibitor GW4869. When taken up by floxed reporter
cells, exosomes containing WW-Cre were capable of inducing DNA recombination,
indicating functional delivery of the protein to recipient cells. Engineered
exosomes were administered to the brain of transgenic reporter mice using the
nasal route to test for intracellular protein delivery in vivo. This resulted in
the transport of engineered exosomes predominantly to recipient neurons in a
number of brain regions, including the olfactory bulb, cortex, striatum,
hippocampus, and cerebellum. The ability to engineer exosomes to deliver
biologically active proteins across the blood-brain barrier represents an
important step for the development of therapeutics to treat brain diseases.
PMID- 28412170
TI - Lipid Nanoparticle Systems for Enabling Gene Therapies.
AB - Genetic drugs such as small interfering RNA (siRNA), mRNA, or plasmid DNA provide
potential gene therapies to treat most diseases by silencing pathological genes,
expressing therapeutic proteins, or through gene-editing applications. In order
for genetic drugs to be used clinically, however, sophisticated delivery systems
are required. Lipid nanoparticle (LNP) systems are currently the lead non-viral
delivery systems for enabling the clinical potential of genetic drugs.
Application will be made to the Food and Drug Administration (FDA) in 2017 for
approval of an LNP siRNA drug to treat transthyretin-induced amyloidosis,
presently an untreatable disease. Here, we first review research leading to the
development of LNP siRNA systems capable of silencing target genes in hepatocytes
following systemic administration. Subsequently, progress made to extend LNP
technology to mRNA and plasmids for protein replacement, vaccine, and gene
editing applications is summarized. Finally, we address current limitations of
LNP technology as applied to genetic drugs and ways in which such limitations may
be overcome. It is concluded that LNP technology, by virtue of robust and
efficient formulation processes, as well as advantages in potency, payload, and
design flexibility, will be a dominant non-viral technology to enable the
enormous potential of gene therapy.
PMID- 28412172
TI - New yeast models for studying mitochondrial morphology as affected by oxidative
stress and other factors.
AB - The overwhelming majority of investigations on mitochondrial morphology were
performed using S. cerevisiae. In this study we showed the benefits of applying
new model organisms including petite-negative D. magnusii and Y. lipolytica
yeasts for visualization of mitochondrial fragmentation. Normally giant D.
magnusii cells and filament-like Y. lipolytica cells contain the highly
structured mitochondrial reticulum. Oxidative stress mediated by tert-butyl
hydroperoxide triggered mitochondrial fragmentation in yeasts. In D. magnusii
mitochondrial fragmentation was also induced by impairing the oxidative
phosphorylation system. Higher prooxidant concentrations caused cell death.
Cationic lipophilic antioxidant SkQ1 acted downstream of the excessive ROS
production and prevented partially or almost totally oxidative stress and related
mitochondrial fragmentation and cell death. We believe that utility of D.
magnusii and Y. lipolytica yeasts as a "living test tube" would be useful for
providing new information concerning the interplay between mitochondrial dynamics
and mitochondrial dysfunction, cell cycle, aging, mitophagy and cell death.
PMID- 28412171
TI - Gender-Specific Amelioration of SMA Phenotype upon Disruption of a Deep Intronic
Structure by an Oligonucleotide.
AB - Spinal muscular atrophy (SMA), the leading genetic disease of children, is caused
by low levels of survival motor neuron (SMN) protein. Here, we employ A15/283, an
antisense oligonucleotide targeting a deep intronic sequence/structure, to
examine the impact of restoration of SMN in a mild SMA mouse model. We show
gender-specific amelioration of tail necrosis upon subcutaneous administrations
of A15/283 into SMA mice at postnatal days 1 and 3. We also demonstrate that a
modest increase in SMN due to early administrations of A15/283 dramatically
improves testicular development and spermatogenesis. Our results reveal near
total correction of expression of several genes in adult testis upon temporary
increase in SMN during early postnatal development. This is the first
demonstration of in vivo efficacy of an antisense oligonucleotide targeting a
deep intronic sequence/structure. This is also the first report of gender
specific amelioration of SMA pathology upon a modest peripheral increase of SMN.
PMID- 28412174
TI - Experimentally determined tilt and bending moduli of single-component lipid
bilayers.
AB - Values of the bending modulus KC and the tilt modulus Ktheta are reported for
single component lipid bilayers. The lipids studied have the common names DOPC,
DMPC, diC22:1PC, SOPC, POPC, diPhyPC, DLPC, DPPC, DHPC and DEPC, listed in the
order of number of samples examined. The experimental method, thus far the only
one that measures the tilt modulus of lipid bilayers, first obtains diffuse X-ray
scattering data from oriented stacks of bilayers. The values of the moduli emerge
from fitting the data to the accepted tilt-dependent continuum model for the free
energy of a single bilayer, further enhanced by interactions between bilayers in
the stack. The results indicate the broad trend that the tilt modulus for these
PC lipids is smaller the closer the temperature is to the main transition
temperature. Another trend is that inclusion of tilt raises the value of the
bending modulus more for lipids with smaller values of the tilt modulus. Values
of both moduli are compared to recent literature values obtained from simulations
and values of the bending modulus are compared to the literature values obtained
by other experimental methods.
PMID- 28412173
TI - Spontaneous formation of single component liposomes from a solution.
AB - The diameter of lipid vesicles is generally known to be determined by parameters
external to the system, such as fluid shear, electric fields, co-surfactants,
etc. We present a mechanism by which a system consisting of a single component
lipid can spontaneously assemble from a solution phase to form monodisperse
unilamellar vesicles of well-defined diameters dictated only by thermodynamic
parameters intrinsic to the system. Here, the lipids self-assemble as vesicles
when an aqueous phase diffusively replaces the original solvent in a
macroscopically stationary (or quiescent) manner. We demonstrate this using
phosphatidyl choline lipid-ethanol-water systems, where the average diameter of
the liposomes is shown to be intrinsic, in reasonable agreement with the
Helfrich's model of the vesicle free energy. The size depends only on the
temperature and the lipid type, eliminating dependence on kinetic effects or
external forcing normally observed. The method provides the first pure system to
study the self-assembly of vesicle-forming surfactants; and with a natural
thermodynamic length scale, it may have an implication for the vesicle size
selection under pre-biotic conditions.
PMID- 28412175
TI - Legionnaires' disease from a dental unit. Chicken-and-egg or a different source
entirely?
PMID- 28412177
TI - Educational programme to enhance stethoscope hygiene behaviour.
PMID- 28412176
TI - Human parvovirus B19 nosocomial outbreak in healthcare personnel in a paediatric
ward at a national tertiary referral centre in Thailand.
AB - BACKGROUND: Nosocomial outbreaks of parvovirus B19 (pB19) have been reported, but
they rarely occur among healthcare personnel (HCP). Susceptibility among pregnant
HCP was the major concern. METHODS: An outbreak of pB19 among HCP is described in
a paediatric ward with a cross-sectional serologic study in all HCP and patients
exposed to the outbreak. Acute infection was diagnosed by polymerase chain
reaction or positive anti-parvovirus B19 IgM. FINDINGS: Among 48 HCP (three
pregnant) and 22 patients included in the outbreak serologic study, 11 (23%) HCP
and two (9%) patients had acute infection. Of these, six HCP and no patients were
symptomatic. Clinical manifestations included itchy rash (100%) and joint pain
following resolution of rash (67%), with median rash duration of four days. Forty
percent of HCP and 50% of patients had positive anti-parvovirus IgG, indicating
previously immune status. HCP with acute infection and HCP who were susceptible
without infection were younger than HCP with previous immunity (mean age 32.2 vs
40.5 years, respectively; P = 0.003). The attack rate was 38% among HCP and 18%
among patients who were susceptible, respectively. The outbreak ended within two
weeks following strict droplet precaution and segregation of symptomatic HCP.
CONCLUSION: Parvovirus B19 infection may cause nosocomial outbreak with high
attack rate among HCP. Outbreak control with droplet precaution was highly
effective.
PMID- 28412178
TI - Universal screening and decolonization for control of MRSA in nursing homes:
follow-up of a cluster randomized controlled trial.
AB - In 2010-11, a trial conducted in nursing homes showed no benefit of meticillin
resistant Staphylococcus aureus (MRSA) universal screening and decolonization
over standard precautions to reduce the prevalence of MRSA carriage. Accordingly,
no routine screening was performed from 2012. A five-year follow-up shows no new
evidence supporting the intervention. Recommendations issued after trial (no
screening and decolonization of MRSA residents) were retained.
PMID- 28412179
TI - Unsafe waste management practices and hepatitis C among hospital sanitary staff
in Pakistan.
PMID- 28412180
TI - Computational fluid dynamics study of the pharyngeal airway space before and
after mandibular setback surgery in patients with mandibular prognathism.
AB - The purpose of this study was to investigate the relationship between the
pressure drop in the pharyngeal airway space (DeltaPPAS) and the minimum cross
sectional area (minCSA) of the pharyngeal airway before and after mandibular
setback surgery using computational fluid dynamics, in order to prevent
iatrogenic obstructive sleep apnoea. Eleven patients with mandibular prognathism
underwent bilateral sagittal split osteotomy for mandibular setback. Three
dimensional models of the upper airway were reconstructed from preoperative and
postoperative computed tomography images, and simulations were performed using
computational fluid dynamics. DeltaPPAS and the minCSA of the pharyngeal airway
were calculated, and the relationship between them was evaluated by non-linear
regression analysis. In all cases, the minCSA was found at the level of the
velopharynx. After surgery, DeltaPPAS increased significantly and the minCSA
decreased significantly. The non-linear regression equation expressing the
relationship between these variables was DeltaPPAS=3.73*minCSA-2.06. When the
minCSA was <1cm2, DeltaPPAS increased greatly. The results of this study suggest
that surgeons should consider bimaxillary orthognathic surgery rather than
mandibular setback surgery to prevent the development of iatrogenic obstructive
sleep apnoea when correcting a skeletal class III malocclusion.
PMID- 28412181
TI - Maxilla reconstruction with autogenous bone block grafts: computed tomography
evaluation and implant survival in a 5-year retrospective study.
AB - This retrospective study was performed to evaluate the bone thickness of the
anterior maxillary region after reconstruction with autogenous bone blocks at 6
months and 5 years after surgery using computed tomography (CT) and to determine
the implant survival rate. Eleven patients with a horizontal bone deficiency were
treated with reconstructive procedures and implant placement. CT measurements
were obtained before surgery (T0) and at 6 months (T1) and 5 years (T2) after
surgery. The values were analysed statistically (analysis of variance and Tukey's
test; P<0.05). Implant survival was evaluated at follow-up. The mean width of the
lower region of the ridge (+/-standard deviation, in millimetres) was 3.8+/-1.6
at T0, 7.0+/-1.6 at T1, and 6.5+/-1.0 at T2; the mean width of the upper region
of the ridge was 5.7+/-2.3 at T0, 8.3+/-2.2 at T1, and 7.3+/-1.6 at T2. The mean
total thickness of the ridge was 4.7mm at T0, 7.6mm at T1, and 6.9mm at T2; the
average increase in horizontal thickness was 2.9mm at T1 and 2.2mm at T2. A
statistically significant difference was observed in the mean width of the lower
portion at T1 and T2 compared to the width at T0. The implant survival rate was
94.1%. This technique demonstrated high predictability for implant survival, with
a reduction in the graft bone during the follow-up period.
PMID- 28412182
TI - Characterization of three small molecule inhibitors of enterovirus 71 identified
from screening of a library of natural products.
AB - Enterovirus 71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD).
Infection with EV-A71 is more often associated with neurological complications in
children and is responsible for the majority of fatalities, but currently there
is no approved antiviral therapy for treatment. Here, we identified auraptene,
formononetin, and yangonin as effective inhibitors of EV-A71 infection in the low
micromolar range from screening of a natural product library. Among them,
formononetin and yangonin selectively inhibited EV-A71 while auraptene could
inhibit viruses within the enterovirus species A. Time of addition studies showed
that all the three inhibitors inhibit both attachment and postattachment step of
entry. We found mutations conferring the resistance to these inhibitors in the
VP1 and VP4 capsid proteins and confirmed the target residues using a reverse
genetic approach. Interestingly, auraptene- and formononetin-resistant viruses
exhibit cross-resistance to other inhibitors while yangonin-resistant virus still
remains susceptible to auraptene and formononetin. Moreover, auraptene and
formononetin, but not yangonin protected EV-A71 against thermal inactivation,
indicating a direct stabilizing effect of both compounds on virion capsid
conformation. Finally, neither biochanin A (an analog of formononetin) nor DL
Kavain (an analog of yangonin) exhibited anti-EV-A71 activity, suggesting the
structural elements required for anti-EV-A71 activity. Taken together, these
compounds could become potential lead compounds for anti-EV-A71 drug development
and also serve as tool compounds for studying virus entry.
PMID- 28412184
TI - Clinical trial research in focus: why do so many clinical trials fail in IPF?
PMID- 28412183
TI - Structure-activity relationship analysis of mitochondrial toxicity caused by
antiviral ribonucleoside analogs.
AB - Recent cases of severe toxicity during clinical trials have been associated with
antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have
hypothesized that the active metabolites of toxic ribonucleoside analogs, the
triphosphate forms, inadvertently target human mitochondrial RNA polymerase
(POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis.
Others have proposed that the prodrug moiety released from the ribonucleoside
analogs might instead cause toxicity. Here, we report the mitochondrial effects
of several clinically relevant and structurally diverse ribonucleoside analogs
including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of
balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094). We found that
efficient substrates and chain terminators of POLRMT, such as the nucleoside
triphosphate forms of R1479, NITD-008, and INX-08189, are likely to cause
mitochondrial toxicity in cells, while weaker chain terminators and inhibitors of
POLRMT such as T-705 ribonucleoside triphosphate do not elicit strong in vitro
mitochondrial effects. Within a fixed 3'-deoxy or 2'-C-methyl ribose scaffold,
changing the base moiety of nucleotides did not strongly affect their inhibition
constant (Ki) against POLRMT. By swapping the nucleoside and prodrug moieties of
PSI-7851 and INX-08189, we demonstrated that the cell-based toxicity of INX-08189
is mainly caused by the nucleoside component of the molecule. Taken together,
these results show that diverse 2' or 4' mono-substituted ribonucleoside
scaffolds cause mitochondrial toxicity. Given the unpredictable structure
activity relationship of this ribonucleoside liability, we propose a rapid and
systematic in vitro screen combining cell-based and biochemical assays to
identify the early potential for mitochondrial toxicity.
PMID- 28412185
TI - Coexistence of risk behaviors for being overweight among Brazilian adolescents.
AB - This study aimed to evaluate the magnitude of and the factors associated with the
coexistence of risk behaviors for being overweight among Brazilian adolescents.
This is a cross-sectional study with a representative sample of adolescents
(mostly aged 13-15years) enrolled from public and private schools of Brazil in
2012. The co-occurring sedentary behavior and inadequate food consumption
(regular intake of sugary and fried foods, and irregular consumption of fruits
and vegetables-FV) was estimated using a Venn diagram. Sociodemographic,
familial, and behavioral factors associated with the number of risk behaviors for
being overweight were identified using an ordinal logistic regression analysis.
Sedentary behavior was observed in 62.0% of adolescents. Regular intake of sugary
or fried food was observed in 55.3% and 23.5% of adolescents, respectively, with
51.9% having an inadequate intake of FV. At least one risk behavior was reported
in >90.0% of adolescents; 6.1% reported all 4. Being female, having a higher
maternal education level, attending private school, not having breakfast or meals
with parents regularly, eat watching television, and not practicing weekly
leisure time physical activity were associated with an increased chance of having
multiple risk behaviors. This study observed a high prevalence of coexisting of
risk behaviors, which was associated with sociodemographic, familial, and
behavioral factors. These findings may contribute to a clearer understanding of
the associations between different behaviors among adolescents, and may be used
to improve public health surveillance and to develop strategies that address
multiple behaviors, in order to prevent overweight among adolescents.
PMID- 28412186
TI - Cardiorespiratory fitness, physical activity and cancer mortality in men.
AB - The preventive role of cardiorespiratory fitness (CRF) and physical activity (PA)
in cancer mortality is not well-established. This study sought to evaluate the
association between CRF, PA and cancer mortality in men. Maximal exercise testing
was performed at the VA Palo Alto Health Care System in 5876 male veterans
(60.5+/-11years) free from malignancy at baseline who were followed for mean of
9.9 (range 0.11 to 26.8) years. PA status was assessed in a sub-group of 4034
participants. Relative risks and population attributable risks (PAR%) for cancer
related mortality were determined. During the follow-up, 447 men (7.6%) died from
cancer. Forty-nine percent of the sample was considered physically active
(defined as meeting the minimal PA guidelines); this group exhibited a 20%
reduction in cancer mortality risk [95% confidence interval (0.67-0.97), p=0.02].
CRF was inversely associated with cancer death. For each 1 MET increase in CRF
there was a 5% reduction in risk for cancer mortality (p=0.01). Compared to the
least fit group (<5.0 METs), subjects with moderate to high CRF exhibited 26-46%
reduced risks of cancer mortality (p for trend=0.002). The PARs% for low CRF and
inactivity were 6.6% and 8.5%, respectively. Moderate and high CRF levels and
meeting the minimal PA guidelines have protective benefits against cancer
mortality in men. Eliminating inactivity and low CRF as risk factors could
potentially prevent a considerable number of cancer deaths and reduce the
associated societal and economic burden.
PMID- 28412187
TI - Restoring Volar Tilt in AO Type C2 Fractures of the Distal Radius With Unilateral
External Fixation.
AB - PURPOSE: To determine whether unilateral external fixation using a staged
multiplanar reduction technique restores anatomic volar tilt in a distal radius
fracture model. METHODS: We used radiographic images to obtain baseline
measurements in 20 fresh-frozen cadaveric wrists. Through a standard dorsal
approach to the radius, we performed osteotomies to simulate displaced AO/ASIF
type C2 fractures. After placement of a unilateral external fixator, a stepwise
technique of applying longitudinal traction followed by a volar translational
maneuver was performed. Radiographic imaging was obtained after each step of the
multiplanar reduction technique. RESULTS: Standard longitudinal traction did not
restore volar tilt angles to their baseline measurements. The addition of a volar
translation maneuver had a significant effect on restoring baseline volar tilt.
There was a statistically significant difference in volar tilt measurements
between straight longitudinal traction and volar translation. Radial inclination,
radial height, and ulnar variance did not differ significantly between
longitudinal traction and the addition of volar translation. CONCLUSIONS: A
criticism of traditional external fixation is the inability of longitudinal
ligamentotaxis to attain sagittal plane (volar tilt) reduction of the articular
surface. This study demonstrates that a multiplanar reduction technique using
unilateral external fixation devices on cadaveric distal radius fractures can
achieve an acceptable reduction. CLINICAL RELEVANCE: External fixation of distal
radius fractures may be favorable in situations where soft tissue loss, wound
contamination, and comorbid medical factors preclude the use of internal fixation
techniques. A multiplanar reduction technique using a unilateral external
fixation device may facilitate fracture reduction in acceptable alignment.
PMID- 28412188
TI - Patterns of Brachial Plexus Stretch Palsy in a Prospective Series of 565
Surgically Treated Patients.
AB - PURPOSE: To report the distribution of the different patterns of stretch brachial
plexus injuries (BPIs) in a retrospective cohort of patients operated at our
institution during an 11-year period. METHODS: From September 2002 to June 2012,
we evaluated and operated on 565 patients with traction injuries of the brachial
plexus. Average age was 26.8 years (SD +/-9.3 years); the interval between the
injury and surgery was 5.4 months (SD +/-2.8 months). The pattern of injury was
defined based on data obtained from a standardized clinical examination,
preoperative helical computed tomography myelography after intradural contrast
injection, surgical findings, and intraoperative electric stimulation. RESULTS:
Supraclavicular injuries accounted for 91% of all cases (N = 512) whereas 9% of
injuries were infraclavicular. Within the supraclavicular injuries, 50% of cases
involved the entire plexus and in 12% there was avulsion of all 5 roots. Among
them, 94% involved the upper plexus (C5 to C6 +/- C7 +/- C8), and 6% the lower
plexus (C8 to T1 +/- C7). C5 to C6 injuries accounted for 23% of partial BPI, C5
to C7 19%, C5 to C8 52%, C7 to T1 4%, and C8 to T1 2%. CONCLUSIONS: The most
relevant findings of this study were that most panplexal BPIs showed at least one
graftable root, there was a high prevalence of C5 to C8 BPI, C7 to T1 root injury
was the most common pattern of lower type of injury, and infraclavicular BPI was
uncommon. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.
PMID- 28412189
TI - Mean 5-Year Follow-up for Suture Button Suspensionplasty in the Treatment of
Thumb Carpometacarpal Joint Osteoarthritis.
AB - PURPOSE: Suture button suspensionplasty (SBS) has been used to treat thumb
carpometacarpal joint osteoarthritis (CMC joint OA). Although promising short
term outcomes have been reported, no outcomes beyond 4 years have been published.
The aim of this article is to report intermediate outcomes of SBS. METHODS: We
reviewed the charts of 14 patients who underwent 16 SBS procedures for
symptomatic thumb CMC joint OA. We recorded demographic data, preoperative Eaton
stage, length of follow-up, Quick-Disabilities of the Arm, Shoulder, and Hand
questionnaire scores, as well as pinch strength, grip strength, range of motion,
and metacarpal subsidence. Operative time and postoperative complications were
documented. RESULTS: Average age was 64 years. There were 12 women and 2 men.
Preoperative Eaton stages were III and IV in 8 thumbs each. Mean operative time
was 93 minutes. Mean follow-up was 64 months with mean Quick-Disabilities of the
Arm, Shoulder, and Hand score improvement of 58.2. Mean palmar and radial
abduction were 105% and 97%, respectively, of the nonsurgical thumb. Kapandji
scores for all operated thumbs were either 9 or 10. Pinch and grip strength were
107% and 102%, respectively, of the nonsurgical side. Mean trapezial space height
was 71%. One patient underwent removal of a symptomatic implant and 2 patients
had transient neuropraxia of the dorsal radial sensory nerve. CONCLUSIONS:
Favorable outcomes (improvement in range of motion and pain relief) of SBS remain
durable over time. Our results show that improvement in strength may also be
expected over time when using SBS after trapeziectomy for the treatment of thumb
CMC joint OA. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 28412190
TI - Exogenous growth factor based regenerative therapy in alcoholic cirrhosis
patients renders limited effect on hemostatic elements.
PMID- 28412191
TI - Red cell distribution width (RDW) is associated with cardiovascular disease risk
in Crohn's disease.
PMID- 28412192
TI - Association analysis of RAC1 single nucleotide polymorphisms with ulcerative
colitis.
PMID- 28412193
TI - Translational Research - Effective Communication and Teaching Strategies for
Improving the Quality of Pediatric Nursing Care for Hospitalized Children and
Their Families.
PMID- 28412194
TI - Parents find medical errors and safety incidents that hospitals miss.
PMID- 28412195
TI - Neutrophil-lymphocyte ratio predicts hospital-acquired bacterial infections in
decompensated cirrhosis.
AB - BACKGROUND: Bacterial infection is a frequent complication and severe burden in
cirrhotic patients. We determined the utility of neutrophil-to-lymphocyte ratio
(NLR) to predict the hospital-acquired (HA) bacterial infections episode in
patients with decompensated cirrhosis. METHODS: We retrospectively included 2066
consecutive decompensated cirrhotic patients from two separate tertiary
hospitals, divided into training (n=1377) and validation (n=689) set. All data
were collected on admission and all overt bacterial infections occurring after
>48h of hospital stay were registered. RESULTS: The incidence of HA bacterial
infections in training and validation cohort was 35.87% and 31.05% respectively.
Multivariate analysis showed that total bilirubin (TBil), albumin, white blood
cell count (WBC) and NLR were independent predictors of HA bacterial infections.
We established a Model_NTWA using these four variables and a Model_TWA which did
not include NLR. Areas under the curves (AUC) of Model_NTWA (0.859) and NLR
(0.824) were higher than which of Model_TWA (0.713), WBC (0.675), TBil (0.593)
and Albumin (0.583). Consistent with training cohort, validation cohort showed
similar results. Patients with NLR of at least 4.33 had a significantly lower
survival (P<0.001). CONCLUSIONS: NLR can be used as a novel noninvasive marker to
predict the occurrence of HA bacterial infections in decompensated cirrhotic
patients.
PMID- 28412196
TI - Non-enzymatic glycation enhances human serum albumin binding capacity to sodium
fluorescein at room temperature: A spectroscopic analysis.
AB - BACKGROUND: Sodium fluorescein (SF) is a fluorescent tracer dye used extensively
in diagnostic tools in the field of Ophthalmology, particularly in intravenous
fluorescein angiography (IVFA). The binding of SF to human serum albumin (HSA)
has been predicted by molecular docking and investigated by circular dichroism
(CD) and fluorescence spectroscopy with or without glycation at temperatures 296,
301, and 310K. METHODS: The binding parameters were calculated by quenching of
emission spectrum of a constant concentration of SF (2MUmol/l) at 513nm against
increasing concentrations of glycated or unmodified HSA as quencher starting from
stoichiometry ratio of 1:1. RESULTS: The HSA-SF interaction found to be a static
binding. The Stern-Volmer constants (Ksv) were in the range of ~104M-1 and other
thermodynamic parameters like enthalpy (DeltaH degrees ), free energy (DeltaG
degrees ) and entropy (DeltaS degrees ) are similar to albumin ligand bindings
reported by previous workers. CONCLUSIONS: The interactions were found to be
spontaneous, irrespective of temperature or glycation. Glycated HSA is clinically
used to monitor unstable glycemic controls in diabetic patients. A 39% increase
in binding affinity (log K) and free energy (DeltaG degrees ) is reported on
glycation at 310K (room temperature), which may be important in the SF based
angiographies. On glycation HSA-SF binding appears to change from an enthalpy
driven to an entropy-driven reaction. SF shows best binding to FA binding site
III of HSA, which also overlaps with drug binding site II of subdomain IIIA.
Leu430 seems to play a pivotal role in the interaction.
PMID- 28412198
TI - Potential role of lycopene in targeting proprotein convertase subtilisin/kexin
type-9 to combat hypercholesterolemia.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of
the proprotien convertase (PC) family that has profound effects on plasma low
density lipoprotein cholesterol (LDL-C) levels, the major risk factor for
coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R)
protein degradation and reduced recycling to the surface of hepatocytes. Thus,
the current study was premeditated not only to evaluate the role of lycopene in
targeting the inhibition of PCSK-9 via modulation of genes involved in
cholesterol homeostasis in HFD rats but also to examine a correlation between HFD
induced inflammatory cascades and subsequent regulation of PCSK-9 expression.
Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for
PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular
informatics approach to assess the dual mode of action of lycopene in LDL-R
recycling and increased removal of circulatory LDL-C. We for the first time
deciphered that lycopene treatment significantly down-regulates the expression of
hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up
regulated. Furthermore, lycopene ameliorated inflammation stimulated expression
of PCSK-9 via suppressing the expression of inflammatory markers. The results
from our molecular informatics studies confirmed that lycopene, while occupying
the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to
complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex
formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A
complex. Based on above results, it can be concluded that lycopene exhibits
potent hypolipidemic activities via molecular mechanisms that are either
identical (HMGR inhibition) or distinct from that of statins (down-regulation of
PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report
that lycopene has this specific biological property. Being a natural, safer and
alternative therapeutic agent, lycopene could be used as a complete regulator of
cholesterol homeostasis and ASCVD.
PMID- 28412197
TI - An UPLC-MS/MS method for the quantification of BRAF inhibitors (vemurafenib,
dabrafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) in human
plasma. Application to treated melanoma patients.
AB - Targeted therapies for cancers are fast-growing therapies. For instance kinase
inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are
increasingly used to treat malignant melanoma. The metabolic profile of these
drugs can result in great interindividual variability, justifying therapeutic
drug monitoring (TDM). We describe a rapid and specific method for quantification
of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and
binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with
CORTECS C18+ column, under a gradient of 10% acetic acid in water/acetonitrile.
An Acquity-TQD(r) with electrospray ionization was used for detection. Samples
were prepared by solid phase extraction (Oasis(r) MCX microElution) before
injection in the system. Calibration curves ranges from 0.4 to 100MUg/ml for
vemurafenib, from 1 to 1000ng/ml for dabrafenib, from 0.5 to 500ng/ml for
cobimetinib and binimetinib, and from 0.75 to 250ng/ml for trametinib. At all
concentrations the bias was within +/-15% of the nominal concentrations and
precision was <=15%. All results were within the acceptance criteria of the EMA
guidelines on method validation. This rapid, sensitive and specific UPLC-MS/MS
method can perform simultaneous quantification of targeted therapies used in
malignant melanoma and is usable for routine TDM.
PMID- 28412199
TI - The AtrbohF-dependent regulation of ROS signaling is required for melatonin
induced salinity tolerance in Arabidopsis.
AB - Although several literatures confirmed the beneficial roles of exogenous
melatonin in the enhancement of salinity tolerance in plants, whether or how
endogenous melatonin confers plant salinity tolerance is still elusive. In the
report, we observed impaired melatonin level and salinity hypersensitivity in
atsnat, the Arabidopsis melatonin synthesis mutant. Above hypersensitivity was
rescued by melatonin or hydrogen peroxide. Meanwhile, melatonin-mediated salt
tolerance in wild-type was abolished by an NADPH oxidase inhibitor, suggesting
the possible role of NADPH oxidase-dependent reactive oxygen species (ROS).
Genetic evidence further showed that the rapid stimulated RbohF transcripts and
production of ROS elicited by melatonin in stressed wild-type plants were largely
abolished by the mutation of AtrbohF. Meanwhile, salinity sensitivity of atrbohF
mutant was not altered by melatonin, which was consistent with the higher Na+
content and the resulting greater Na+/K+ ratio, compared with those in wild-type
plants. Further changes of SOS1, SOS2, and SOS3 transcripts suggested that the
melatonin-triggered SOS-mediated Na+ efflux might be mediated by AtrbohF
dependent ROS. The addition of melatonin could intensify the increased
antioxidant defence in stressed wild-type but not in atrbohF mutant, both of
which were confirmed by the histochemical staining for ROS production and lipid
peroxidation during the later period of stress. Collectively, our genetic and
molecular evidence revealed that the AtrbohF-dependent ROS signaling is required
for melatonin-induced salinity tolerance via the reestablishment of ion and redox
homeostasis.
PMID- 28412200
TI - Three-year follow-up of children with abnormal newborn screening results for
congenital hypothyroidism.
AB - BACKGROUND: To analyze predictive factors suggesting transient congenital
hypothyroidism (TCH) compared to permanent congenital hypothyroidism (PCH) or
transient thyroid function test (TFT) abnormalities among children who had
positive screening results at our centers over the past decade. METHODS: A
retrospective chart review of 105 subjects who presented elevated TSH levels on a
newborn screening test (NST) was done. TCH was defined when a trial-off therapy
was successful, and PCH was defined when a trial failed or when the subject was
kept on medication beyond 3 years of age. A transient TFT abnormality was defined
when follow-up TFTs were normalized without levothyroxine (LT4) therapy. RESULTS:
Congenital hypothyroidism (CH) was diagnosed in 75.2% (TCH 35.2% and PCH 40.0%)
of all subjects; the others (24.8%) showed transient TFT abnormalities. Initial
NST-TSH levels (optimal cutoff point, 31.0 MUIU/mL), the LT4 dose at 2 years of
age (4.1 MUg/kg/day), and the maximal LT4 dose (50 MUg/day) merged as significant
predictive factors discriminating between TCH and PCH. The initial serum level of
free T4 (1.06 ng/dL) and not TSH (27.2 MUIU/mL) was the only discriminating
factor between transient TFT abnormalities and TCH. CONCLUSION: Earlier re
evaluation might be possible when a patient's initial NST-TSH levels and maximal
or 2-year LT4 doses are low, as both are important predictors of successful trial
off therapy in CH patients. When the initial serum level of free T4 is above the
average value in neonates with mildly elevated TSH levels, TFTs may be more
likely to normalize on their own.
PMID- 28412201
TI - Nitric oxide enhanced the growth of an obligated intracellular bacterium Orientia
tsutsugamushi in murine macrophages.
AB - Orientia tsutsugamushi is the causative agent of scrub typhus. It is an obligate
intracellular bacterium that grows only in eukaryotic cells. Macrophages play an
important role in innate immunity by surveilling the human body for pathogens. In
present study, it was demonstrated that O. tsutsugamushi propagated well in LPS
activated RAW 264.7 macrophages, but not in non-activated macrophages. In LPS
activated macrophages, the expression of Nos2, which encodes the inducible nitric
oxide (NO) synthase (iNOS), was highly upregulated compared to those in non
activated macrophages. Parallel to this upregulation, high NO production was
observed in LPS-activated macrophages. Transmissible electron microscopy showed
that O. tsutsugamushi replicated in the cytosol of macrophages. Thus, O.
tsutsugamushi was thought to escape the phagosomes at an early stage of phagosome
maturation to avoid the bactericidal effect of NO. Furthermore, O. tsutsugamushi
growth was enhanced in NO donor-supplied RAW 264.7 macrophages, as well as in LPS
activated, but not in non-activated macrophages. Consequently, these results
suggested that NO was rather essential for enhancing the replication of O.
tsutsugamushi in RAW 264.7 macrophages, despite the typically detrimental effects
of NO against intracellular pathogens. In the present study, NO was suggested to
activate specific pathways to enhance the growth of O. tsutsugamushi.
PMID- 28412202
TI - The immunosuppressive effects of a novel recombinant LipQ (Rv2485c) protein of
Mycobacterium tuberculosis on human macrophage cell lines.
AB - Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a
major global health challenge. A number of mycobacterial macromolecules have been
shown to target biological processes within host macrophages; however, the exact
mechanism for the majority of these host pathogen interactions is still poorly
understood. Moreover, the lipid metabolic pathway is one of the most important
physiologic pathways that plays a vital role in the survival and infection of
Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ
from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro.Our
results demonstrate that rLipQ significantly lowers the expression level of pro
inflammatory cytokines (TNF-alpha& IFN-gamma) and augments the level of anti
inflammatory cytokines such as IL-4 & IL-10as compared to LPS stimulated
macrophages. An up-regulation of anti-inflammatory and down-regulation of pro
inflammatory cytokines levels in rLipQ pretreated macrophages implies immuno
modulatory functions in TB patients. Interestingly, rLipQ also inhibited the
expression of iNOS, TLR-2 and transcription factor NF-kB in LPS stimulated
macrophages whereas the expression of TLR-4 remains unchanged. The inhibition in
the expression of these signaling molecules has been correlated to the inhibition
of NO production in macrophages. Taken together, these studies demonstrate that
rLipQ is a novel lipase that is highly immunogenic and may play an important role
in the virulence and pathogenesis of M. tuberculosis infection, by altering the
balance of cytokines, which might help to assess prognosis and contribute to a
better understanding against host-pathogen interactions.
PMID- 28412203
TI - ATP-sensitive inwardly rectifying potassium channel modulators alter cardiac
function in honey bees.
AB - ATP-sensitive inwardly rectifying potassium (KATP) channels couple cellular
metabolism to the membrane potential of the cell and play an important role in a
variety of tissue types, including the insect dorsal vessel, making them a
subject of interest not only for understanding invertebrate physiology, but also
as a potential target for novel insecticides. Most of what is known about these
ion channels is the result of work performed in mammalian systems, with insect
studies being limited to only a few species and physiological systems. The goal
of this study was to investigate the role that KATP channels play in regulating
cardiac function in a model social insect, the honey bee (Apis mellifera), by
examining the effects that modulators of these ion channels have on heart rate.
Heart rate decreased in a concentration-dependent manner, relative to controls,
with the application of the KATP channel antagonist tolbutamide and KATP channel
blockers barium and magnesium, whereas heart rate increased with the application
of a low concentration of the KATP channel agonist pinacidil, but decreased at
higher concentrations. Furthermore, pretreatment with barium magnified the
effects of tolbutamide treatment and eliminated the effects of pinacidil
treatment at select concentrations. The data presented here confirm a role for
KATP channels in the regulation of honey bee dorsal vessel contractions and
provide insight into the underlying physiology that governs the regulation of bee
cardiac function.
PMID- 28412204
TI - A calcineurin antifungal strategy with analogs of FK506.
AB - A novel antifungal strategy targeting the inhibition of calcineurin is described.
To develop a calcineurin based inhibitor of pathogenic fungi, analogs of FK506
were synthesized that were able to permeate mammalian but not fungal cells.
Antagonists in combination with FK506 were not immunosuppressive and retained
antifungal activity in A. fumigatus. To reduce the dosage burden of the
antagonist, murine oral PK was improved an order of magnitude relative to
previous FK506 antagonists.
PMID- 28412205
TI - SLC2A1/GLUT1 expression in mural nodules of intraductal papillary mucinous
neoplasm of the pancreas.
AB - In intraductal papillary mucinous neoplasms (IPMNs), the presence of a mural
nodule showing a papillary or nodular proliferation of tumor cells in the dilated
pancreatic duct is an indication for resection of IPMN. Solute carrier family 2,
facilitated glucose transporter member 1, known as glucose transporter type 1
(SLC2A1/GLUT1) mediates cellular glucose uptake in many carcinomas and is
correlated with increased 18F-fluorodeoxyglucose (18F-FDG) uptake. We examined
SLC2A1/GLUT1 expression in the mural nodules of 180 IPMN specimens to distinguish
malignant/benign tumors. A mural nodule was detected in 80 (44.4%) of the IPMNs,
and was detected in 18.6% (13/70) of the IPMN-low (dysplasia) specimens, 36.1%
(13/36) of the IPMN-int, 93.3% (28/30) of the IPMN-high, and 59.1% (26/44) of the
IPMN-inv (with an associated invasive carcinoma) specimens. The sensitivity for
detecting mural nodules was 81.7% by endoscopic ultrasonography, 70% by contrast
enhanced computed tomography and 54% by endoscopic retrograde
cholangiopancreatography. SLC2A1/GLUT1 expression in the mural nodules was
recognized in the basal and basolateral cytomembrane of tumor cells and was
expressed in 15.4% (2/13) of the IPMN-low, 15.4% (2/13) of the IPMN-int, 71.4%
(20/28) of the IPMN-high and 84.6% (22/26) of the IPMN-inv groups. The
SLC2A1/GLUT1 expression was significantly higher in the IPMN-high and IPMN-inv
mural nodules than in those of the IPMN-low and IPMN-int groups. Our findings
suggest that SLC2A1/GLUT1 is expressed late in the adenoma-carcinoma sequence
during carcinogenesis in IPMN, and SLC2A1/GLUT1 act as therapeutic target for
malignant IPMN.
PMID- 28412206
TI - Cicatricial variant of cryptogenic organizing pneumonia.
AB - This study of 12 patients focused on a variant of cryptogenic organizing
pneumonia (COP) labeled the cicatricial form in which the airspaces of the lung
are filled with and consolidated by dense collagenized scar tissue associated
with preservation of underlying lung architecture. Patients were predominantly
middle-aged men and presented with bilateral lung disease in the majority of
cases, often with nodular or reticulonodular disease (10/12; 83%). Patients were
usually symptomatic with shortness of breath, cough, and dyspnea on exertion.
Fifty-five percent of patients (6/11) had persistent or progressive disease at
follow-up (mean, 68.5 months; median, 110 months). The cicatricial variant of
cryptogenic organizing pneumonia may be predictive of a more recalcitrant form of
COP that needs to be morphologically separated from classical COP, usual
interstitial pneumonia, and nonspecific interstitial pneumonia.
PMID- 28412208
TI - High expression of P2X7R is an independent postoperative indicator of poor
prognosis in colorectal cancer.
AB - The purinergic P2X7 receptor (P2X7R) is a master regulator of inflammation and
inflammation-related diseases. Recently, P2X7R has been reportedly involved in
carcinogenesis and tumor progression. In this study, we investigated the
expression pattern and prognostic merit of P2X7R in human colorectal cancer
(CRC). The expression profile of P2X7R in 12 pairs of CRC and non-tumorous
specimens was evaluated using Western blotting analysis. Additionally, we
performed immunohistochemistry (IHC) on 116 paraffin-embedded CRC specimens, and
evaluated the correlation between P2X7R expression and clinicopathological
factors. P2X7R was overexpressed in CRC samples, compared with adjacent non
tumorous ones. High P2X7R expression significantly correlated with tumor size (P
= .0177), Lymph node metastasis (P = .0128), and TNM stage (P = .0081).
Furthermore, univariate and multivariate Cox regression analyses revealed that
P2X7R expression could serve as an independent prognostic factor for poor overall
survival (P = .0197). Treatment with P2X7R agonist BzATP led to the activation of
Akt and NF-kappaB pathways. Consequently, we revealed that BzATP accelerated the
proliferation of CRC cells, whereas co-incubation with PI3K/Akt inhibitor
LY294002 significantly impaired BzATP-induced proliferation of CRC cells. Our
findings implied that P2X7R may serve as a valuable prognostic indicator and
promising therapeutic target of CRC.
PMID- 28412207
TI - MicroRNA 183 family profiles in pheochromocytomas are related to clinical
parameters and SDHB expression.
AB - This study aims to examine the expression profiles of the miR-183 cluster (miR
96/182/183) in pheochromocytoma. Pheochromocytoma tissues were prospectively
collected from 50 patients with pheochromocytoma. Expression of miR-183 cluster
members and SDHB protein expression were analyzed in these tissues by
quantitative real-time polymerase chain reaction and immunohistochemistry,
respectively. The expression of miR-183 cluster members in pheochromocytomas was
correlated with the clinical and pathological parameters of these patients. The
expression levels of miR-183 cluster members were predominantly downregulated or
deleted in pheochromocytoma. Low expression or deletion of miR-96 was
predominantly noted in younger patients with pheochromocytoma (<50 years, P=.01).
Female patients in the study group showed marked deletion of miR-182 (P=.05).
Deletion of the cluster was also associated with SDHB protein expression in
pheochromocytoma. Moreover, patients with low miR-183 cluster expression had a
slightly better survival rate when compared with patients with high expression.
To conclude, the findings indicate a role for miR-183 cluster members in the
pathogenesis and clinical progression of pheochromocytoma.
PMID- 28412209
TI - Mortalin expression in pancreatic cancer and its clinical and prognostic
significance.
AB - Mortalin, an essential mitochondrial chaperone protein, is involved in the
tumorigenesis of a number of malignancies. This study aimed to investigate the
expression of Mortalin in pancreatic ductal adenocarcinoma (PDAC) cells and to
determine its clinicopathological and prognostic significance. The localization
of Mortalin protein was detected in BXPC-3 PDAC cells using immunofluorescence.
Immunohistochemistry was also used to detect Mortalin expression in well-defined
tissues obtained from 106 PDAC patients and 46 corresponding nontumor pancreatic
tissues. Clinicopathological parameters and overall survival data were collected
and compared between different Mortalin statuses. The results of
immunohistochemistry and immunofluorescence showed that Mortalin was primarily
present in the cytoplasm of PDAC cells. The ratio of strong positive staining for
Mortalin was higher in PDAC tissues (55.66%; 59/106) than in normal adjacent
tissues (23.91%; 11/46). Positive relationships between Mortalin expression and
clinical stage, perineural invasion, lymph node metastasis, and lower overall
survival were observed. Multivariate Cox regression analysis identified Mortalin
as a significant independent prognostic factor, in addition to location, clinical
stage, and perineural invasion, for survival of PDAC patients. Therefore, we
present strong evidence that Mortalin may function as a practical marker to
predict prognosis and as a potential therapeutic target in PDAC treatment.
PMID- 28412210
TI - IMP3 expression in biopsy specimens as a diagnostic biomarker for colorectal
cancer.
AB - No single biological marker is used in routine diagnosis of colorectal cancer
(CRC) in endoscopic biopsies. IMP3 is a good independent prognostic biomarker for
CRC. However, the expression of IMP3 in hyperplastic polyp (HP) and adenoma has
not yet been studied. Moreover, no studies have established the diagnostic value
of IMP3 in biopsies. This study aims to assess IMP3 expression in HP, adenoma,
and CRC in resection specimens and to investigate its value in diagnosis of CRC
in biopsies. A total of 1328 specimens (633 of polypectomy, 395 surgical
resections, 300 biopsies) were retrospectively analyzed. IMP3 expression was
observed in 0 of 197 (0%) normal tissues, 0 of 130 (0%) HPs, 14 of 504 (2.8%)
adenomas, and 139 of 197 (70.6%) CRCs. IMP3 was found to be overexpressed in CRC
compared with adenoma (P<.001). Among the 300 biopsies, 56 were diagnosed as
adenoma, and 244 were CRCs. Of the 56 adenoma cases, 22 (39.3%) were confirmed,
whereas 34 (60.7%) were diagnosed as CRC in resection specimens. All 244 CRC
biopsies were confirmed by resection specimens. IMP3-positive expression was
observed in 204 of 300 (68.0%) biopsies, including in 22 of 56 (39.3%) adenomas
and 182 of 244 (74.6%) CRCs. All IMP3-positive expressions in the biopsies were
finally diagnosed as CRC. Our findings demonstrated that IMP3 is a reliable
marker for the diagnosis of CRC in endoscopic biopsies.
PMID- 28412211
TI - Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response
and prognosis in stage II/III breast cancer.
AB - The predictive value of serum miRNAs (ser-miRNA) for the response to neoadjuvant
chemotherapy (NCT) and the prognosis of breast cancer patients were investigated
in the current study. The study included 118 stage II/III breast cancer patients
and 30 healthy adult women. Peripheral blood was drawn from participants before
the start (baseline [BL]), at the end of the second cycle (first evaluation
during NCT [FEN]), and at the end of NCT (second evaluation during NCT [SEN]).
The expression of ser-miRNAs was examined by quantitative reverse-transcription
polymerase chain reaction (qRT-PCR), and their association with chemotherapy
response and prognosis was analyzed. MiR-19a, miR-21, miR-125b, miR-155, miR-205,
and miR-373 were significantly up-regulated in the serum of breast cancer
patients at BL, miR-451 was significantly down-regulated, and miR-122 was
unchanged compared with the levels in healthy women. The expression of ser-miR
125b and the changes of ser-miR-21 expression during NCT were associated with
chemotherapy response and disease-free survival (DFS). In chemotherapy
responders, ser-miR-125b expression was lower than that of non-responders at BL,
FEN, and SEN, and ser-miR-21 levels decreased from BL to FEN and from BL to SEN.
Survival analysis showed that patients with lower ser-miR-125b expression at BL,
FEN, and SEN had favorable DFS, and those with decreased ser-miR-21 expression
from BL to FEN and from BL to SEN had better DFS. In conclusion, ser-miR-21 and
ser-miR-125b were identified as novel, noninvasive predictive markers for NCT
response and prognosis in breast cancer.
PMID- 28412212
TI - Mucoepidermoid carcinoma with extensive spindled morphology and melanocytic
marker expression.
AB - Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of the
salivary gland. Albeit common, histologic variants have rarely been noted in MEC.
Here, we report a 49-year-old man with a sublingual gland tumor. Histologically,
the tumor was composed of spindle cells arranged in interlacing fascicules or
globular nests. A few bland small glands containing mucous cells were also
scattered. The spindle tumor cells completely lacked immunoreactivity for
cytokeratin, and exhibited immunoreactivity for vimentin, S-100, HMB-45, Melan A,
and SOX10. The tumor was initially suspected to be clear cell sarcoma, malignant
melanoma, or perivascular epithelioid cell tumor with a few entrapped
nonneoplastic duct epitheliums. However, reverse-transcription polymerase chain
reaction revealed the CRTC3-MAML2 fusion gene product diagnostic of MEC. In fact,
a very minor component of the epithelial cells was reminiscent of conventional
MEC, whereas major spindled tumor cells possessed markedly altered
differentiation. This is the first case report of MEC with extensive spindled
morphology and melanocytic marker expression.
PMID- 28412213
TI - Acute mast cell leukemia associated with t(4;5)(q21;q33).
AB - To the best of our knowledge, this manuscript describes clinical and pathologic
findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33),
compatible with fusion of the PDGFRB gene to a rare partner, PRKG2. Translocation
involving the PDGFRB gene is confirmed by fluorescence in situ hybridization
study. This case presented a relatively fulminant clinical course with acute mast
cell leukemia and "C" findings (cytopenia, hepatosplenomegaly, and weight loss),
mast cell sarcoma, and severe basophilia. Despite aggressive presentation
initially, the patient responded well to tyrosine kinase inhibitor treatment and
is currently in complete remission 33 months after diagnosis. This case
significantly extends the disease spectrum associated with PRKG2/PDGFRB fusion
gene. Recognizing the whole spectrum of diseases associated with this fusion is
critical because tyrosine kinase inhibitor treatment has been exceedingly
effective in these patients.
PMID- 28412214
TI - Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of
non-small cell lung cancer via inhibition of transforming growth factor beta1
signaling pathway in vitro and in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Bu-Fei decoction
(BFD) has been utilized to treat patients with Qi deficiency for decades, with
the advantages of invigorating vital energy, clearing heat-toxin and moistening
lung, etc. According to previous clinical experience and trials, BFD has been
found to indeed improve life quality of lung cancer patients and prolong survival
time. Nevertheless, little is known on its potential mechanisms so far. Being
regarded as a pivotal cytokine in the tumor microenvironment, transforming growth
factor beta (TGF-beta) stands out as a robust regulator of epithelial-mesenchymal
transition (EMT), which is closely linked to tumor progression. AIM OF THE STUDY:
The present study was designed to explore whether BFD antagonized EMT via
blocking TGF-beta1-induced signaling pathway, and then help contribute to create
a relatively steady microenvironment for confining lung cancer. MATERIALS AND
METHODS: This experiment was performed in lung adenocarcinoma A549 cells both in
vitro and in vivo. In detail, the influences mediated by TGF-beta1 alone or in
combination with different concentrations of BFD on migration were detected by
wound healing and transwell assays, and the effects of BFD on cell viability were
determined by cell counting kit-8 (CCK-8) assay. TGF-beta1, EMT relevant proteins
and genes were evaluated by western blotting, confocal microscopy, quantitative
real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and
enzyme-linked immuno sorbent assay (ELISA). Female BALB/C nude mice were
subcutaneously implanted A549 cells and given BFD by gavage twice daily for 28
days. The tumor volume was monitored every 4 days to draw growth curve. The tumor
weight, expression levels of EMT-related protein in tumor tissues and TGF-beta1
serum level were evaluated, respectively. RESULTS: BFD only exerted minor effects
on A549 cell proliferation and this was in accordance with the in vivo result,
which showed that the tumor growth and weight were not be restrained by BFD
administration. However, the data elucidated that BFD could dose-dependently
suppress EMT induced by TGF-beta1 in vitro via attenuating canonical Smad
signaling pathway. In the A549 xenograft mouse model, BFD also inhibited protein
markers that are associated with EMT and TGF-beta1 secretion into serum.
CONCLUSIONS: Based on these above data, the conclusion could be put forward that
BFD probably attenuated TGF-beta1 mediated EMT in A549 cells via decreasing
canonical Smad signaling pathway both in vitro and in vivo, which may help
restrain the malignant phenotype induced by TGF-beta1 in A549 cells to some
extent.
PMID- 28412215
TI - Involvement of serotonergic, noradrenergic and dopaminergic systems in the
antidepressant-like effect of ginsenoside Rb1, a major active ingredient of Panax
ginseng C.A. Meyer.
AB - ETHNOPHARMACOLOGY RELEVANCE: Ginsenoside Rb1, a 20 (S)-protopanaxadiol, is a
major active ingredient of Panax ginseng C.A. Meyer, which as the King of Chinese
herbs, has been wildly used for the treatment of central nervous system diseases.
Previous studies have shown that 20 (S)-protopanaxadiol possesses a novel
antidepressant-like effect in the treatment of depression, whereas ginsenoside
Rb1 in depression has been rarely reported. AIM OF THE REVIEW: The present study
was to investigate the antidepressant-like effect of ginsenoside Rb1 and its
relevant mechanisms. MATERIALS AND METHODS: The whole experiment was divided into
two parts: one part we examined the antidepressant-like effect of ginsenoside Rb1
with open-field test (OFT), tail suspension test (TST), forced swim test (FST), 5
HTP induced head-twitch and reserpine response in mice, another part we used
chronic unpredicted mild stress (CUMS) model to further explore the
antidepressant-like effect of ginsenoside Rb1 with caffeine, fluoxetine and p
Chlorophenylalanine (PCPA) in rats. Furthermore, the levels of monoamine
neurotransmitters of NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, HVA were
all measured by ELISA kits after the CUMS protocol. RESULTS: Our data indicated
that 7 days treatment with ginsenoside Rb1 (4, 8, 10mg/kg, p.o.) significantly
decreased immobility time in the FST and TST in mice, and played important roles
in mice which were induced by 5-HTP (200mg/kg, i.p.) and reserpine (4mg/kg,
i.p.). On the basis of CUMS model, 21 days treatment with ginsenoside Rb1 not
only had effective interactions with caffeine (5mg/kg, i.p.), fluoxetine (1mg/kg,
i.p.) and PCPA (100mg/kg, i.p.), but also significantly up-regulated the 5-HT, 5
HIAA, NE and DA levels in CUMS rats' brain, whereas HVA and DOPAC had no
significant difference. Moreover, there was no alteration in spontaneous
locomotion in any experimental group. CONCLUSIONS: These results suggest that
ginsenoside Rb1 exhibits significant antidepressant-like effect in behavioral
tests, chronic animal model and drug interactions, its mechanisms mainly mediated
by central neurotransmitters of serotonergic, noradrenergic and dopaminergic
systems.
PMID- 28412216
TI - Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post
ischemic pain by activation of pro-resolving pathways.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris Sw. is widely used in popular
medicine to treat conditions associated with pain. AIM OF THE STUDY: The present
study investigated the influence of hydroalcoholic crude extract of Casearia
sylvestris (HCE-CS) and contribution of pro-resolving mediators on mechanical
hyperalgesia in a mouse model of chronic post-ischemia pain (CPIP). METHODS AND
RESULTS: Male Swiss mice were subjected to ischemia of the right hind paw (3h),
then reperfusion was allowed. At 10min, 24h or 48h post-ischemia/reperfusion
(I/R), different groups of animals were treated with HCE-CS (30mg/Kg, orally
[p.o]), selected agonists at the pro-resolving receptor ALX/FPR2 (natural
molecules like resolvin D1 and lipoxin A4 or the synthetic compound BML-111; 0.1
1ug/animal) or vehicle (saline, 10mL/Kg, s.c.), in the absence or presence of the
antagonist WRW4 (10ug, s.c.). Mechanical hyperalgesia (paw withdrawal to von Frey
filament) was asseseed together with histological and immunostainning analyses.
In these settings, pro-resolving mediators reduced mechanical hyperalgesia and
HCE-CS or BML-111 displayed anti-hyperalgesic effects which was markedly
attenuated in animals treated with WRW4. ALX/FPR2 expression was raised in
skeletal muscle or neutrophils after treatment with HCE-CS or BML-111.
CONCLUSION: These results reveal significant antihyperalgesic effect of HCE-CS on
CPIP, mediated at least in part, by the pathway of resolution of inflammation
centred on the axis modulated by ALX/FPR2.
PMID- 28412217
TI - Dalbergia odorifera extract promotes angiogenesis through upregulation of VEGFRs
and PI3K/MAPK signaling pathways.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a
Chinese herbal medicine commonly used for the treatment of various ischemic
diseases in Chinese medicine practice. AIM OF THE STUDY: In this study,
therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were
investigated on transgenic zebrafish in vivo and human umbilical vein endothelial
cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE
on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and
intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE
on HUVECs were examined by MTT, scratch assay, protein chip and western blot.
RESULTS: In the in vivo studies, we found that DOE was able to dose-dependently
promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore
the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of
VEGFRs including kdr, kdrl and flt-1 induced by VEGF receptor kinase inhibitor II
(VRI). In the in vitro studies, we observed that DOE promoted the proliferation,
migration of HUVECs and also restored the injury induced by VRI. Moreover,
protein chip and western blot experiments showed the PI3K/MAPK cell
proliferation/migration pathway were activated by DOE. CONCLUSIONS: DOE has a
therapeutic effects on angiogenesis, and its mechanism may be related to
adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These
results suggest a strong potential for Dalbergia odorifera to be developed as an
angiogenesis-promoting therapeutic.
PMID- 28412218
TI - Evaluation of the combined use of metronomic zoledronic acid and Coriolus
versicolor in intratibial breast cancer mouse model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Coriolus versicolor (CV) is a mushroom
traditionally used for strengthening the immune system and nowadays used as
immunomodulatory adjuvant in anticancer therapy. Breast cancer usually
metastasizes to the skeleton, interrupts the normal bone remodeling process and
causes osteolytic bone lesions. The aims of the present study were to evaluate
its herb-drug interaction with metronomic zoledronate in preventing cancer
propagation, metastasis and bone destruction. MATERIALS AND METHODS: Mice
inoculated with human breast cancer cells tagged with a luciferase (MDA-MB-231
TXSA) in tibia were treated with CV aqueous extract, mZOL, or the combination of
both for 4 weeks. Alteration of the luciferase signals in tibia, liver and lung
were quantified using the IVIS imaging system. The skeletal response was
evaluated using micro-computed tomography (micro-CT). In vitro experiments were
carried out to confirm the in vivo findings. RESULTS: Results showed that
combination of CV and mZOL diminished tumor growth without increasing the
incidence of lung and liver metastasis in intratibial breast tumor model. The
combination therapy also reserved the integrity of bones. In vitro studies
demonstrated that combined use of CV and mZOL inhibited cancer cell proliferation
and osteoclastogenesis. CONCLUSIONS: These findings suggested that combination
treatment of CV and mZOL attenuated breast tumor propagation, protected against
osteolytic bone lesion without significant metastases. This study provides
scientific evidences on the beneficial outcome of using CV together with mZOL in
the management of breast cancer and metastasis, which may lead to the development
of CV as adjuvant health supplement for the control of breast cancer.
PMID- 28412219
TI - Medicinal plant uses and names from the herbarium of Francesc Bolos (1773-1844).
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotany takes into account past uses to be
projected into the present and future. Most current ethnobotanical research is
focused, especially in industrialised countries, on obtaining information of
plant uses from elderly people. Historical ethnobotany is less cultivated,
although papers have demonstrated its interest. Particularly poor, but
potentially very relevant, is the attention paid to historical herbaria as a
source of data on useful plants. AIMS OF THE STUDY: Bearing this in mind, we
studied the herbarium of the Catalan pharmacist and naturalist Francesc Bolos
(1773-1844), which contains information on medicinal uses and folk names, with
the aim of establishing a catalogue of plants and uses and tracing them through
old and contemporary literature. METHODOLOGY: The ca. 6000 plant specimens of
this herbarium were investigated to assess those including plant uses and names.
These taxa have been thoroughly revised. The data have been tabulated, their
biogeographic profile, possible endemic or threatened status, or invasive
behaviour have been assessed, and the content regarding medicinal uses, as well
as folk names, has been studied. The medicinal terms used have been interpreted
as per current days' medicine. The popular names and uses have been compared with
those appearing in a certain number of works published from 11th to 20th
centuries in the territories covered by the herbarium and with all the data
collected in 20th and 21st centuries in an extensive database on Catalan
ethnobotany. RESULTS: A total of 385 plant specimens (381 taxa) have been
detected bearing medicinal use and folk names information. We collected data on
1107 reports of plant medicinal properties (in Latin), 32 indications of
toxicity, nine reports of food use, and 123, 302 and 318 popular plant names in
Catalan, Spanish and French, respectively. The most quoted systems are digestive,
skin and subcutaneous tissue (plus traumatic troubles) and genitourinary.
Relatively high degrees of coincidence of plant names and uses in the herbarium
and the literature comparison set have been found. Of the taxa contained in this
medicinal herbarium, 294 were native to the Iberian Peninsula, and 86 were alien.
Neither endemic nor threatened taxa have been detected, whereas a considerable
portion of the alien taxa shows invasive behaviour at present. CONCLUSIONS: Our
analyses indicate a certain degree of consistency between the medicinal uses of
plants recorded in this 18th and 19th century herbarium and the records found in
the literature and in recent ethnobotanical datasets, accounting for the
robustness of pharmaceutical ethnobotanical knowledge in the area considered.
Data appearing on the specimen labels are numerous, pointing out the herbarium as
a relevant source of ethnopharmacological information. Special attention should
be paid to some original uses contained in the herbarium's labels for further
investigation on plant properties and drug design.
PMID- 28412221
TI - Opportunities for women in sport in Brazil: Expectations after Rio 2016.
PMID- 28412220
TI - Inflammation-induced GluA1 trafficking and membrane insertion of Ca2+ permeable
AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis
factor, PI3 kinase and protein kinase A.
AB - Peripheral inflammation induces sensitization of nociceptive spinal cord neurons.
Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca2+
permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant
pain behavior, molecular mechanisms connecting these two events have not been
studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw
carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and
GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected
rats compared to controls. In the same tissue, GluA2 levels were not altered.
Inflammation-induced increases in membrane GluA1 were prevented by i.t. pre
treatment with antagonists to TNF, PI3K, PKA and NMDA. Interestingly,
administration of TNF or PI3K inhibitors followed by carrageenan caused a marked
reduction in plasma membrane GluA2 levels, despite the fact that membrane GluA2
levels were stable following inhibitor administration in the absence of
carrageenan. TNF pre-incubation induced increased numbers of Co2+ labeled dorsal
horn neurons, indicating more neurons with Ca2+ permeable AMPAr. In parallel to
Western blot results, this increase was blocked by antagonism of PI3K and PKA. In
addition, spinal slices from GluA1 transgenic mice, which had a single alanine
replacement at GluA1 ser 845 or ser 831 that prevented phosphorylation, were
resistant to TNF-induced increases in Co2+ labeling. However, behavioral
responses following intraplantar carrageenan and formalin in the mutant mice were
no different from littermate controls, suggesting a more complex regulation of
nociception. Co-localization of GluA1, GluA2 and GluA4 with synaptophysin on
identified spinoparabrachial neurons and their relative ratios were used to
assess inflammation-induced trafficking of AMPAr to synapses. Inflammation
induced an increase in synaptic GluA1, but not GluA2. Although total GluA4 also
increased with inflammation, co-localization of GluA4 with synaptophysin, fell
short of significance. Taken together these data suggest that peripheral
inflammation induces a PI3K and PKA dependent TNFR1 activated pathway that
culminates with trafficking of calcium permeable AMPAr into synapses of
nociceptive dorsal horn projection neurons.
PMID- 28412223
TI - Bioengineered robust hybrid hydrogels enrich the stability and efficacy of
biological drugs.
AB - Biological drugs are exquisitely tailored components offering the advantages of
high specificity and efficacy that are considered safe for treating diseases.
Nevertheless, the effectiveness of biological drugs is limited by their inherent
short biological half-life and poor stability in vivo. Herein, we engineered a
novel delivery platform based on hybrid injectable hydrogels, in which pH- and
temperature-responsive biodegradable copolymers were site-specifically coupled to
the sulfhydryl group of human serum albumin, which effectively enhances the
stability and circulation half-life of the biological drug, recombinant uricase
enzyme (Uox). The albumin ligand conjugated to the Uox allowed specific-binding
of the enzyme within the protein shell, and the synthetic polymers effectively
shield the protein-enzyme complex. Such close confinement exhibits strong
resistance towards various physical, chemical and therapeutically relevant
stressors such as temperature, pH and proteases. Subcutaneous administration of
Uox-loaded bioengineered hybrid hydrogel improved the pharmacokinetics by
prolonging its circulation half-life. As a consequence, the bioengineered hybrid
hydrogel normalized the serum uric acid level in hypoxanthine/potassium oxonate
induced hyperuricemia mice, and no obvious side effects were observed in the
major organs. The characteristic of the bioengineered hydrogel networks
applicable to a variety of biological drugs by simple mixing that unlock the
possibility of adapting biological drugs to therapeutic applications.
PMID- 28412222
TI - Targeted drug distribution in tumor extracellular fluid of GD2-expressing
neuroblastoma patient-derived xenografts using SN-38-loaded nanoparticles
conjugated to the monoclonal antibody 3F8.
AB - Neuroblastoma is a pediatric solid tumor with high expression of the tumor
associated antigen disialoganglioside GD2. Despite initial response to induction
therapy, nearly 50% of high-risk neuroblastomas recur because of chemoresistance.
Here we encapsulated the topoisomerase-I inhibitor SN-38 in polymeric
nanoparticles (NPs) surface-decorated with the anti-GD2 mouse mAb 3F8 at a mean
density of seven antibody molecules per NP. The accumulation of drug-loaded NPs
targeted with 3F8 versus with control antibody was monitored by microdialysis in
patient-derived GD2-expressing neuroblastoma xenografts. We showed that the
extent of tumor penetration by SN-38 was significantly higher in mice receiving
the targeted nano-drug delivery system when compared to non-targeted system or
free drug. This selective penetration of the tumor extracellular fluid translated
into a strong anti-tumor effect prolonging survival of mice bearing GD2-high
neuroblastomas in vivo.
PMID- 28412224
TI - Mechanism-based selection of stabilization strategy for amorphous formulations:
Insights into crystallization pathways.
AB - We developed a step-by-step experimental protocol using differential scanning
calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy
(PLM) and a small-scale dissolution apparatus (MUDISS Profiler) to investigate
the mechanism (solid-to-solid or solution-mediated) by which crystallization of
amorphous drugs occurs upon dissolution. This protocol then guided how to
stabilize the amorphous formulation. Indapamide, metolazone, glibenclamide and
glipizide were selected as model drugs and HPMC (Pharmacoat 606) and PVP (K30) as
stabilizing polymers. Spray-dried amorphous indapamide, metolazone and
glibenclamide crystallized via solution-mediated nucleation while glipizide
suffered from solid-to-solid crystallization. The addition of 0.001%-0.01% (w/v)
HPMC into the dissolution medium successfully prevented the crystallization of
supersaturated solutions of indapamide and metolazone whereas it only reduced the
crystallization rate for glibenclamide. Amorphous solid dispersion (ASD)
formulation of glipizide and PVP K30, at a ratio of 50:50% (w/w) reduced but did
not completely eliminate the solid-to-solid crystallization of glipizide even
though the overall dissolution rate was enhanced both in the absence and presence
of HPMC. Raman spectroscopy indicated the formation of a glipizide polymorph in
the dissolution medium with higher solubility than the stable polymorph. As a
complementary technique, molecular dynamics (MD) simulations of indapamide and
glibenclamide with HPMC was performed. It was revealed that hydrogen bonding
patterns of the two drugs with HPMC differed significantly, suggesting that
hydrogen bonding may play a role in the greater stabilizing effect on
supersaturation of indapamide, compared to glibenclamide.
PMID- 28412226
TI - Expression profiling-based clustering of healthy subjects recapitulates
classifications defined by clinical observation in Chinese medicine.
AB - Differences between healthy subjects and associated disease risks are of
substantial interest in clinical medicine. Based on clinical presentations,
Traditional Chinese Medicine (TCM) classifies healthy people into nine
constitutions: Balanced, Qi, Yang or Yin deficiency, Phlegm-dampness, Damp-heat,
Blood stasis, Qi stagnation, and Inherited special constitutions. In particular,
Yang and Yin deficiency constitutions exhibit cold and heat aversion,
respectively. However, the intrinsic molecular characteristics of unbalanced
phenotypes remain unclear. To determine whether gene expression-based clustering
can recapitulate TCM-based classification, peripheral blood mononuclear cells
(PBMCs) were collected from Chinese Han individuals with Yang/Yin deficiency (n =
12 each) and Balanced (n = 8) constitutions, and global gene expression profiles
were determined using the Affymetrix HG-U133A Plus 2.0 array. Notably, we found
that gene expression-based classifications reflected distinct TCM-based subtypes.
Consistent with the clinical observation that subjects with Yang deficiency tend
toward obesity, series-clustering analysis detected several key lipid metabolic
genes (diacylglycerol acyltransferase (DGAT2), acyl-CoA synthetase (ACSL1), and
ATP-binding cassette subfamily A member 1 (ABCA1)) to be down- and up-regulated
in Yin and Yang deficiency constitutions, respectively. Our findings suggest that
Yin/Yang deficiency and Balanced constitutions are unique entities in their mRNA
expression profiles. Moreover, the distinct physical and clinical characteristics
of each unbalanced constitution can be explained, in part, by specific gene
expression signatures.
PMID- 28412227
TI - Generation of thermosensitive male-sterile maize by targeted knockout of the
ZmTMS5 gene.
PMID- 28412225
TI - Enhancing tissue permeability with MRI guided preclinical focused ultrasound
system in rabbit muscle: From normal tissue to VX2 tumor.
AB - High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing
physical energy based modality to ablate solid tumors with high power, or
increase local permeability in tissues/tumors in pulsed mode with relatively low
power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU
(pHIFU) is present in the majority of novel applications recently developed for
enhancing the delivery of drugs and genes. Previous studies have demonstrated the
capability of pHIFU to change tissue local permeability for enhanced drug
delivery in both mouse tumors and mouse muscle. Further study based on bulk
tissues in large animals and clinical HIFU system revealed correlation between
therapeutic effect and thermal parameters, which was absent in the previous mouse
studies. In this study, we further investigated the relation between the
therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues
based on a rabbit model and a preclinical HIFU system. Correlation between
therapeutic effect and thermal parameters was confirmed in our study on the same
bulk tissues although different HIFU systems were used. Following the study in
bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors
implanted on both hind limbs of rabbits and investigated the feasibility to
enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU
technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was
used following pHIFU treatment in our study to target VX2 tumor and serve as the
radiotracer for follow-up single-photon emission computed tomography (SPECT)
scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA
in the area of VX2 tumors pretreated by pHIFU compared with the control VX2
tumors not being pretreated by pHIFU, and statistical analysis revealed averaged
34.5% enhancement 24h after systematic delivery of 111In-DOTA-IA in VX2 tumors
pretreated by pHIFU compared with the control VX2 tumors.
PMID- 28412228
TI - Temperature effect on CRISPR-Cas9 mediated genome editing.
AB - Zinc-finger nuclease (ZFN), transcription activator-like effector nuclease
(TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR
associated protein 9 (CRISPR-Cas9) are the most commonly used genome editing
tools. Previous studies demonstrated that hypothermia treatment increased the
mutation rates induced by ZFNs and TALENs in mammalian cells. Here, we
characterize the effect of different culture temperatures on CRISPR-Cas9 mediated
genome editing and find that the genome editing efficiency of CRISPR-Cas9 is
significantly hampered by hypothermia treatment, unlike ZFN and TALEN. In
addition, hyperthermia culture condition enhances genome editing by CRISPR-Cas9
in some cell lines, due to the higher enzyme activity and sgRNA expression level
at higher temperature. Our study has implications on CRISPR-Cas9 applications in
a broad spectrum of species, many of which do not live at 37 degrees C.
PMID- 28412231
TI - Prenatal imaging presentation of Meckel diverticulum.
PMID- 28412232
TI - Accuracy of video observation and a three-dimensional head tracking system for
detecting and quantifying robot-simulated head movements in cone beam computed
tomography.
AB - OBJECTIVES: To assess the accuracy of detecting robot-simulated head movements
using video observation (VO) and 3-dimensional head tracking (HT) in a cone beam
computed tomography examination setup. STUDY DESIGN: A mannequin head was mounted
on a robot that was programmed to simulate patient head movements. Six types of
movement (tremor, nodding, lateral rotation, lifting, swallowing, and
anteroposterior translation), 3 distances (0.25, 1, and 5 mm), and 2 speeds (1
and 5 mm/s) were tested in triplicate (108 examinations). An additional 18 videos
and HT of no-motion served as controls for a total of 126 examinations. Three
blinded observers viewed video recordings of the examinations, scoring whether
the head moved and the movement type. HT provided quantitative measures of
movement distance. Accuracy, sensitivity, and specificity for movement detection
by VO and HT were calculated, related to true type, distance, and speed of
movement. Differences between the true and the measured movement distances were
assessed for HT. RESULTS: VO movement detection presented accuracy of 0.86,
sensitivity of 0.85, and specificity of 0.94. Anteroposterior translation (33.3%)
and 0.25 mm movements (41.7%) were often not detected by VO. HT correctly
detected all cases (accuracy = 1). HT presented small differences between the
true and the measured movement distances (average 20-54 MUm). CONCLUSIONS: VO
missed 41.7% of the 0.25 mm movements. HT correctly detected all movements and
quantified movements with an average error <55 MUm.
PMID- 28412229
TI - Characteristics and Factors Associated With Pain in Older Homeless Individuals:
Results From the Health Outcomes in People Experiencing Homelessness in Older
Middle Age (HOPE HOME) Study.
AB - : Individuals experiencing homelessness in the United States are aging; little is
known about chronic pain in this population. In a cross-sectional, population
based study, we interviewed 350 homeless individuals aged 50 years and older to
describe pain experienced by older persons experiencing homelessness and to
assess factors associated with chronic moderate to severe pain, defined as pain
lasting >=3 months, with a past week average severity score of 5 to 10 (scale 0
10). The median age of participants was 58 years. Participants were predominantly
African American (79.6%) and male (77.3%). Overall, 46.8% reported chronic
moderate to severe pain. Almost half of participants reported a diagnosis of
arthritis (44.3%) and one-third reported symptoms consistent with post-traumatic
stress disorder (PTSD; 32.8%). Three-quarters (75.3%) endorsed a personal history
of abuse. In multivariate analyses, PTSD (adjusted odds ratio [AOR]: 2.2, 95%
confidence interval [CI], 1.4-3.7), arthritis (AOR: 4.8, 95% CI, 3.0-7.8), and
history of experiencing abuse (AOR: 2.4, 95% CI, 1.3-4.3) were associated with
chronic moderate to severe pain. HIV status, diabetes, depressive symptoms, and
substance use were not associated with pain. Clinicians should consider the
management of associated mental health conditions and the sequelae of
experiencing abuse in the treatment of chronic pain in older adults experiencing
homelessness. PERSPECTIVE: This article describes the prevalence and factors
associated with chronic pain in older homeless adults. Almost half report chronic
pain, which was associated with PTSD, arthritis, and personal history of abuse.
Clinicians should address chronic pain, trauma, and the associated mental health
conditions in this high-risk population.
PMID- 28412230
TI - Oral health 4 life: Design and methods of a semi-pragmatic randomized trial to
promote oral health care and smoking abstinence among tobacco quitline callers.
AB - Smokers are at high risk for oral disease. As a result, they represent an
important target group for population-level, public oral health promotion
efforts. While dental health professionals often address smoking with their
patients, no systematic efforts have been made to offer smokers an intervention
to improve their use of oral health care. This paper details the rationale,
design, and methods of a large, semi-pragmatic, randomized clinical trial
designed to address this gap. Participants are recruited via the Oregon, Nebraska
and Louisiana state-sponsored tobacco quitlines and randomized to receive
standard quitline care versus standard care plus a multi-modal oral health
promotion program (Oral Health 4 Life) integrated within the quitline services.
All participants are followed for 6months to assess the impact of the
intervention on smoking abstinence and utilization of professional dental care.
In addition, the study will assess the cost of the intervention and provide
practical guidance to states on whether the intervention is financially feasible
to implement, should the intervention be effective. This study protocol may be
useful to others interested in promoting oral health among smokers, those
interested in partnering with tobacco quitlines to extend standard services to
address other high risk health behaviors among smokers, or those interested in
semi-pragmatic trial design.
PMID- 28412233
TI - Importance of tumor extent in adenosquamous carcinoma of the head and neck: a
retrospective cohort study.
AB - OBJECTIVE: The aim of this study was to determine the correlates of survival for
patients diagnosed with adenosquamous carcinoma (ASC) of the head and neck. STUDY
DESIGN: Patients diagnosed with ASC of the head and neck between 1973 and 2012
were identified from the Surveillance, Epidemiology, and End Results (SEER)
database. Kaplan-Meier and Cox proportional hazard regression analyses were
conducted to investigate the prognostic factors and treatment modalities that
determine overall survival (OS) and disease-specific survival (DSS). RESULTS: In
the analysis, of the 235 patients diagnosed with adenosquamous of the head and
neck, 66.8% were male and 33.2% were female with a median age at diagnosis of 64
years. Kaplan-Meier analysis determined 5-year survival rates of 30% for OS and
50% for DSS. Univariate and multivariate analyses found that age at diagnosis,
tumor size, tumor extent of disease, surgical resection, and radiation therapy
were independent predictors of OS and DSS. CONCLUSIONS: This study, to our
knowledge, is the largest study, to date, determining the correlates of survival
for ASC of the head and neck. Older age at diagnosis, larger tumor size, and
further extent of disease were correlated with decreased survival. Surgical
resection improves survival in patients with localized or regional disease,
whereas radiation therapy confers survival benefit in patients with distant
extent.
PMID- 28412234
TI - Premolar autotransplantation in juvenile dentition: quantitative assessment of
vertical bone and soft tissue growth.
AB - OBJECTIVE: Premolar autotransplantation represents an effective therapeutic
option for the treatment of juvenile dentition with either aquired or congenital
hypodontia. The objective of this prospective clinical study was to
quantitatively assess bone and soft tissue levels after autogenous premolar
transplantation by clinical and radiographic parameters. STUDY DESIGN: In the
study, 26 premolars were transplanted in 20 patients after traumatic tooth loss
(n = 16) or congenital aplasia (n = 10) in the anterior maxilla. Based on
standardized photographic documentation, the relative soft tissue level was
measured compared to the healthy adjacent teeth. Radiographic findings included
evaluation of root resorption, pulp canal obliteration, and relative bone height.
RESULTS: Average survival rate of transplanted premolars (n = 26) was 100% over a
follow-up period of 29 months (range 10-60 months). The relative soft tissue
level significantly increased by +1.1 mm (P < .01). Radiographs showed a tendency
toward vertical bone growth. Continuous root development and signs of pulpal
healing were observed postoperatively in 18 transplants (69.2%). CONCLUSIONS:
Autogenous premolar transplantation represents a safe method to ensure functional
and aesthetic rehabilitation in the anterior maxilla irrespective of the nature
of tooth loss.
PMID- 28412235
TI - Evaluation of the efficacy of a metal artifact reduction algorithm in different
cone beam computed tomography scanning parameters.
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of a metal artifact
reduction (MAR) algorithm in cone beam computed tomography (CBCT) images of
dental materials obtained with different field-of-view (FOV) and voxel sizes.
STUDY DESIGN: Two imaging phantoms were custom-made of acrylic resin. Each
phantom had 3 cylinders made of the same dental material: dental amalgam or
copper-aluminum alloy. CBCT scans were obtained separately for each of the
imaging phantoms using the Picasso-Trio CBCT (Vatech, Hwaseong, Republic of
Korea) unit at 4 FOV sizes and 2 voxel sizes. Each imaging phantom was scanned
with and without MAR. All images were evaluated in the OnDemand3D software
(Cybermed, Seoul, Republic of Korea) and image noise (gray value variability) was
calculated as the standard deviation (SD) of the gray values of regions of
interest around the dental material cylinders. Data were compared by the Friedman
test and Dunn test (alpha = 0.05). Intraclass correlation coefficient (ICC) was
calculated to assess intraobserver reliability. RESULTS: MAR significantly
reduced (P < .05) image noise around the dental materials, irrespective of FOV
and voxel sizes, with an ICC of 0.997. CONCLUSIONS: The efficacy of MAR was
similar for the different FOV and voxel sizes studied. Hence, imaging protocols
and the use of MAR algorithm should be based on the selection criteria.
PMID- 28412236
TI - Are dental and jaw changes more prevalent in a Brazilian population with sickle
cell anemia?
AB - OBJECTIVE: The aim of this study was to analyze the prevalence of dental and jaw
changes in individuals with sickle cell anemia (SCA) compared with a control
group from a Brazilian population. STUDY DESIGN: This was a retrospective cross
sectional study. Participants were divided into 2 groups: SCA and control (123
patients per group). Intraoral periapical radiographs were taken. Changes in bone
pattern and dental changes were investigated by using the following radiographic
parameters: (1) trabecular bone (step-ladder or spider web); (2) integrity of the
lamina dura (loss of sharpness and continuity, partial or complete absence, and
increased thickness); and (3) dental changes (pulp chamber, root surface,
periapex, dental form, number, and position). Fisher's exact and chi2 tests were
used to compare frequencies and the Mann-Whitney test was used to compare medians
(P < .05). RESULTS: Step-ladder (P < .001) and spider-web patterns (P < .001) in
trabecular bone of the jaw were more common in individuals with SCA than in the
control group. Loss of lamina dura was more frequent in those with SCA than in
control individuals (P = .021). Dental changes were not different between groups
(P > .05), even though the prevalence of hypotaurodontism was twice as high in
the SCA group as in controls (P = .086). CONCLUSIONS: The prevalence of jaw
changes is higher in individuals with SCA.
PMID- 28412237
TI - Reply to: Details of the participants and medical intervention used in the study
evaluating the effect of a mouth exercising device on burning sensation in oral
submucous fibrosis.
PMID- 28412238
TI - Chitosan-modified PLGA nanoparticles tagged with 5TR1 aptamer for in vivo tumor
targeted drug delivery.
AB - In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs)
formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid)
(PLGA) modified with chitosan (CS) through a physical adsorption method. Using
chitosan, the solubility and surface charge of PLGA was modified to make
efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we
developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against
the MUC1 receptor. To prove the MUC1 receptor-mediated uptake of Epi-PLGA-CS-Apt
NPs in the cells, competition experiments were carried out. In vitro experiments,
cytotoxicity assay and fluorescence uptake assay demonstrated that fabricated NPs
with or without aptamers showed significantly high therapeutic efficiency in MCF7
cells (breast cancer cell) compared with free Epi, while in BALB/c mice bearing
C26 cells (murine colon carcinoma cell), targeted NP groups exhibited significant
tumor growth inhibition and higher inclination to tumor compared with non
targeted NPs. Hence, our in vivo results revealed that non-targeted NPs may
diffuse away from the tumor site and release Epi in the extracellular space and
decrease concentration of the drug in the targeted tissue. This study indicated
Epi-PLGA-CS-Apt has great potential as a promising nanoplatform for in vivo
cancer therapy and could be of great value in medical use.
PMID- 28412239
TI - microRNAs as cancer therapeutics: A step closer to clinical application.
AB - During the last decades, basic and translational research has enabled great
improvements in the clinical management of cancer. However, scarcity of complete
remission and many drug-induced toxicities are still a major problem in the
clinics. Recently, microRNAs (miRNAs) have emerged as promising therapeutic
targets due to their involvement in cancer development and progression. Their
extraordinary regulatory potential, which enables regulation of entire signalling
networks within the cells, makes them an interesting tool for the development of
cancer therapeutics. In this review we will focus on miRNAs with experimentally
proven therapeutic potential, and discuss recent advances in the technical
development and clinical evaluation of miRNA-based therapeutic agents.
PMID- 28412240
TI - The level of effort, rather than muscle exercise intensity determines strength
gain following a six-week training.
AB - AIM: This study investigated the effect of voluntary motor effort during a low
intensity (30% maximal voluntary contraction [MVC]) muscle exercise training
program on increasing muscle strength. MATERIALS AND METHODS: Eighteen young and
healthy individuals were randomly assigned to one of three groups: high mental
effort (HME), low mental effort (LME), or a no-training control (CTRL) group.
Training lasted for 6weeks (15min/day, 5days/week). The participants' right-elbow
flexor muscle strength was measured before and after the training program. KEY
FINDINGS: After training, the HME group gained 20.47+/-8.33% (P=0.01) strength
while the LME and CTRL groups had negligible strength changes (1.89+/-0.96% and
3.27+/-2.61%, respectively; P>0.05) despite muscle contraction intensity (30%
MVC) sustained during training was the same for the HME and LME groups. These
results suggest that the level of effort involved in resistance exercise training
plays a critical role in determining the amount of strength augmentation.
SIGNIFICANCE: The finding that high effort combined with low-level physical
exercise training can significantly increase muscle strength has rehabilitation
applications as many patients and frail older adults have difficulties in
participating in high-intensity exercise training such as lifting heavy weights.
High effort plus low-level muscle exercise might serve as a safe training regimen
for effective muscle strengthening in vulnerable populations.
PMID- 28412241
TI - Cathepsin L silencing increases As2O3 toxicity in malignantly transformed
pilocytic astrocytoma MPA58 cells by activating caspases 3/7.
AB - Low-grade, pilocytic astrocytomas are treated by resection, but additional
therapy is necessary for those tumors with anaplastic features. Arsenic trioxide
(As2O3) is emerging as an effective chemotherapeutic agent for treatment of
malignant glioblastoma multiforme, where Cathepsin L silencing enables lower,
less harmful As2O3 concentrations to achieve the desired cytotoxic effect. Here,
we evaluated the effects of As2O3 combined with stable Cathepsin L shRNA
silencing on cell viability/metabolic activity, and apoptosis in primary cultures
of recurrent malignantly transformed pilocytic astrocytoma (MPA). These cells
expressed high Cathepsin L levels, and when grown as monolayers and spheroids,
they were more resistant to As2O3 than the U87MG glioblastoma cell line. Caspases
3/7 activity in MPA58 spheroids was not significantly affected by As2O3, possibly
due to higher chemoresistance of primary biopsy tissue of less malignant
astrocytoma versus the malignant U87MG cell line. However, As2O3 treatment was
cytotoxic to MPA spheroids after silencing of Cathepsin L expression. While
Cathepsin L silencing only slightly decreased the live/dead cell ratio in As2O3
treated MPA-si spheroids under our experimental conditions, there was an increase
in As2O3-mediated apoptosis in MPA-si spheroids, as indicated by elevated
caspases 3/7 activity. Therefore, Cathepsin L silencing by gene manipulation can
be applied when a more aggressive approach is needed in treatment of pilocytic
astrocytomas with anaplastic features.
PMID- 28412242
TI - 14-3-3gamma regulates Copine1-mediated neuronal differentiation in HiB5
hippocampal progenitor cells.
AB - Copine1 (CPNE1), known as a calcium-dependent membrane-binding protein, has
tandem C2 domains and an A domain. We previously demonstrated that CPNE1 directly
induces neuronal differentiation via Protein kinase B (AKT) phosphorylation in
the hippocampal progenitor cell line, HiB5. To better understand its cellular
function, we carried out a yeast two-hybrid screening to find CPNE1 binding
partners. Among the identified proteins, 14-3-3gamma appears to directly interact
with CPNE1. Between CPNE1 and 14-3-3gamma, the physical interaction as well as
the specific binding regions of CPNE1 was confirmed in vitro and in vivo.
Furthermore, among the seven 14-3-3 isotypes, only 14-3-3gamma directly interacts
with CPNE1. Our results also demonstrate that AKT phosphorylation, neurite
outgrowth and expression of the neuronal marker protein are increased when 14-3
3gamma is overexpressed in CPNE1 high expressed HiB5 cells. Furthermore, the
neighboring Ser54 amino acids residue of C2A domain in CPNE1 has an important
role in binding with 14-3-3gamma, and in differentiation-related function of
CPNE1. Moreover, mutation of Ser54 amino acids residue in CPNE1 effectively
decreased association with 14-3-3gamma and neuronal differentiation of HiB5
cells. Collectively, our findings indicate that 14-3-3gamma regulates the
differentiation ability of CPNE1 through the binding with C2A domain of CPNE1 in
HiB5 cells.
PMID- 28412243
TI - Macrophage conditioned medium induced cellular network formation in MCF-7 cells
through enhanced tunneling nanotube formation and tunneling nanotube mediated
release of viable cytoplasmic fragments.
AB - Infiltrating macrophages in tumor microenvironment, through their secreted
cytokines and growth factors, regulate several processes of cancer progression
such as cancer cell survival, proliferation, invasion, metastasis and
angiogenesis. Recently, intercellular cytoplasmic bridges between cancer cells
referred as tunneling nanotubes (TNTs) have been recognized as novel mode of
intercellular communication between cancer cells. In this study, we investigated
the effect of inflammatory mediators present in conditioned medium derived from
macrophages on the formation of TNTs in breast adenocarcinoma cells MCF-7.
Results show that treatment with macrophage conditioned medium (MphiCM) not only
enhanced TNT formation between cells but also stimulated the release of
independently migrating viable cytoplasmic fragments, referred to as microplasts,
from MCF-7 cells. Time lapse microscopy revealed that microplasts were released
from parent cancer cells in extracellular space through formation of TNT-like
structures. Mitochondria, vesicles and cytoplasm could be transferred from parent
cell body to microplasts through connecting TNTs. The microplasts could also be
resorbed into the parent cell body by retraction of the connecting TNTs.
Microplast formation inhibited in presence cell migration inhibitor, cytochalasin
B. Notably by utilizing migratory machinery within microplasts, distantly located
MCF-7 cells formed several TNT based intercellular connections, leading to
formation of physically connected network of cells. Together, these results
demonstrate novel role of TNTs in microplast formation, novel modes of TNT
formation mediated by microplasts and stimulatory effect of MphiCM on cellular
network formation in MCF-7 cells mediated through enhanced TNT and microplast
formation.
PMID- 28412245
TI - CXCR5+CD8+ T cells infiltrate the colorectal tumors and nearby lymph nodes, and
are associated with enhanced IgG response in B cells.
AB - Colorectal cancer is the third most prevalent cancer type worldwide and
contributes to a significant percentage of cancer-related mortality. Recent
studies have shown that the CXCR5+CD8+ T cells present more potent
proinflammatory function than CXCR5-CD8+ T cells in chronic virus infections and
in follicular lymphoma, but the role of CXCR5+CD8+ T cells in colorectal cancer
is yet unclear. In this study, we demonstrated that CXCR5+CD8+ T cells were very
rare in peripheral blood mononuclear cells from healthy and colorectal cancer
individuals, but were significantly enriched in resected tumors and tumor
associated lymph nodes. Compared to CXCR5-CD8+ T cells, the CXCR5+CD8+ T cells
demonstrated significantly higher Bcl-6 expression and lower Blimp1 expression,
suggesting that CXCR5+CD8+ T cells might represent a memory CD8+ T cell subset.
CXCR5+CD8+ T cells also enhanced the IgG expression by autologous B cells. Under
ex vivo condition, the CXCR5+CD8+ T cells demonstrated lower degranulation,
TNFalpha expression and IFNgamma expression than CXCR5-CD8+ T cells. However,
after PMA + ionomycin stimulation, the degranulation and TNFalpha expression by
CXCR5+CD8+ T cells were significantly elevated to a level comparable with CXCR5
CD8+ T cells, whereas the IFNgamma expression by PMA + ionomycin-stimulated
CXCR5+CD8+ T cells were significantly higher than that by CXCR5-CD8+ T cells.
Following long-term TCR-stimulation, CXCR5+CD8+ T cells demonstrated
significantly more potent proliferation capacity and higher IFNgamma expression
than CXCR5-CD8+ T cells. TCR-stimulated CXCR5+CD8+ T cells also showed a gradual
downregulation in CXCR5 expression. We further found that TCR-stimulated
CXCR5+CD8+ T cells demonstrated higher granzyme B production and induced more
specific lysis of autologous tumor cells than CXCR5-CD8+ T cells. Together, these
data demonstrate that CXCR5+CD8+ T cells represent a significant CD8+ T cell
subset in colorectal tumors and have the potential to contribute to antitumor
immunity, but their specific roles require further studies in vivo.
PMID- 28412246
TI - Absence of NUCKS augments paracrine effects of mesenchymal stem cells-mediated
cardiac protection.
AB - Bone marrow-derived mesenchymal stem cells (BM-MSCs) contribute to myocardial
repair after myocardial infarction (MI) by secreting a panel of growth factors
and cytokines. This study was to investigate the potential mechanisms of the
nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS) in
regulation of the profiles of BM-MSCs secretion and compare the therapeutic
efficacy of NUCKS-/-- and wide type-BM-MSCs (WT-BM-MSCs) on MI. The secretion
profiles between NUCKS-/-- and WT-BM-MSCs under hypoxia (1%O2) were analyzed.
Gene function analysis showed that compared with WT-BM-MSCs-conditioned medium
(CdM), some genes over-presented in NUCKS-/--BM-MSCs-CdM were closely associated
with inflammatory response, regulation of cell proliferation, death, migration
and secretion. Notably, VEGFa in NUCKS-/--BM-MSCs-CdM was higher than that of WT
BM-MSCs-CdM. WT-BM-MSCs and NUCKS-/--BM-MSCs were transplanted into the peri
infarct region in mice of MI. At 4 weeks after cell transplantation, NUCKS-/-- or
WT-BM-MSCs group significantly improved heart function and vessels density and
reduced infarction size and apoptosis of cardiomyocytes. Furthermore, NUCKS-/--BM
MSCs provided better cardioprotective effects than WT-BM-MSCs against MI. Our
study demonstrates that depletion of NUCKS enhances the therapeutic efficacy of
BM-MSCs for MI via regulating the secretion.
PMID- 28412244
TI - A central role for cadherin signaling in cancer.
AB - Cadherins are homophilic adhesion molecules with important functions in cell-cell
adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin
accumulates at areas of cell-cell contact, coalesces into macromolecular
complexes to form the adherens junctions (AJs), and associates via accessory
partners with a subcortical ring of actin to form the apical zonula adherens
(ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential
for the overall maintenance and homeostasis of polarized epithelial monolayers.
Its expression is regulated by a host of genetic and epigenetic mechanisms
related to cancer, and its function is modulated by mechanical forces at the
junctions, by direct binding and phosphorylation of accessory proteins
collectively termed catenins, by endocytosis, recycling and degradation, as well
as, by multiple signaling pathways and developmental processes, like the
epithelial to mesenchymal transition (EMT). Nuclear signaling mediated by the
cadherin associated proteins beta-catenin and p120 promotes growth, migration and
pluripotency. Receptor tyrosine kinase, PI3K/AKT, Rho GTPase, and HIPPO
signaling, are all regulated by E-cadherin mediated cell-cell adhesion. Finally,
the recruitment of the microprocessor complex to the ZA by PLEKHA7, and the
subsequent regulation of a small subset of miRNAs provide an additional mechanism
by which the state of epithelial cell-cell adhesion affects translation of target
genes to maintain the homeostasis of polarized epithelial monolayers.
Collectively, the data indicate that loss of E-cadherin function, especially at
the ZA, is a common and crucial step in cancer progression.
PMID- 28412247
TI - Activation of phospholipase C-gamma1 and translocation of phosphatidylinositol
3,4,5-trisphosphate 3-phosphatase contribute to GL-V9-induced apoptosis in human
gastric cancer cells.
AB - Gastric cancer is the most common type of tumor in developing countries and the
fourth most frequently diagnosed cancer worldwide. Here, we demonstrated the
apoptotic effects of GL-V9 on several human gastric cancer cells and selected MGC
803 cells to uncover the underlying mechanism. GL-V9 elevated Bax/Bcl-2 ratio,
abated mitochondrial membrane potential and triggered the onset of apoptotic
execution in MGC-803 cells. Our research revealed that CHOP silencing could not
inhibit apoptosis, neither could it block Ca2+ release, suggesting that GL-V9
induced apoptosis was independent of CHOP. Furthermore, GL-V9 increased
mitochondrial Ca2+ uptake through 1,4,5-triphosphate (IP3) receptor via the
activation of phospholipase C-gamma1 and the translocation of
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase from nucleus to
endoplasmic reticulum. Moreover, in-vivo studies indicated that GL-V9 exhibited
significant MGC-803 xenografts regression in nude mice with low systemic
toxicity. In conclusion, GL-V9 could induce apoptosis in gastric cancer cells,
and would be a promising therapeutical agent against gastric cancer.
PMID- 28412248
TI - Mass Spectrometry Reveals Respiratory Viral Infection Biomarkers.
PMID- 28412250
TI - Mucosal Lining Fluid Biomarkers in Asthma: Basis for Rational Use of New Targeted
Therapies?
PMID- 28412249
TI - The T-LAK Cell-originated Protein Kinase Signal Pathway Promotes Colorectal
Cancer Metastasis.
AB - Approximately 90% of all cancer deaths arise from the metastatic dissemination of
primary tumors. Metastasis is the most lethal attribute of colorectal cancer. New
data regarding the molecules contributing to the metastatic phenotype, the
pathways they control and the genes they regulate are very important for
understanding the processes of metastasis prognosis and prevention in the clinic.
The purpose of this study was to investigate the role of T-LAK cell-originated
protein kinase (TOPK) in the promotion of colorectal cancer metastasis. TOPK is
highly expressed in human metastatic colorectal cancer tissue compared with
malignant adenocarcinoma. We identified p53-related protein kinase (PRPK) as a
new substrate of TOPK. TOPK binds with and phosphorylates PRPK at Ser250 in vitro
and ex vivo. This site plays a critical role in the function of PRPK. Cell lines
stably expressing mutant PRPK (S250A), knockdown TOPK, knockdown PRPK or
knockdown of both TOPK and PRPK significantly inhibited liver metastasis of human
HCT116 colon cancer cells in a xenograft mouse model. Therefore, we conclude that
TOPK directly promotes metastasis of colorectal cancer by modulating PRPK. Thus,
these findings may assist in the prediction of prognosis or development of new
therapeutic strategies against colon cancer.
PMID- 28412253
TI - An Unusual Cause of ST-Segment Elevation Myocardial Infarction.
PMID- 28412251
TI - c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in
Prostate Cancer Affecting Key Gene Networks.
AB - Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The
androgen receptor (AR), a ligand-activated transcription factor, constitutes the
main drug target for advanced cases of the disease. However, a variety of other
transcription factors and signaling networks have been shown to be altered in
patients and to influence AR activity. Amongst these, the oncogenic transcription
factor c-Myc has been studied extensively in multiple malignancies and elevated
protein levels of c-Myc are commonly observed in PCa. Its impact on AR activity,
however, remains elusive. In this study, we assessed the impact of c-Myc
overexpression on AR activity and transcriptional output in a PCa cell line model
and validated the antagonistic effect of c-MYC on AR-targets in patient samples.
We found that c-Myc overexpression partially reprogrammed AR chromatin occupancy
and was associated with altered histone marks distribution, most notably H3K4me1
and H3K27me3. We found c-Myc and the AR co-occupy a substantial number of binding
sites and these exhibited enhancer-like characteristics. Interestingly, c-Myc
overexpression antagonised clinically relevant AR target genes. Therefore, as an
example, we validated the antagonistic relationship between c-Myc and two AR
target genes, KLK3 (alias PSA, prostate specific antigen), and Glycine N
Methyltransferase (GNMT), in patient samples. Our findings provide unbiased
evidence that MYC overexpression deregulates the AR transcriptional program,
which is thought to be a driving force in PCa.
PMID- 28412254
TI - Percutaneous Coronary Intervention for Treatment of Paraganglioma With Coronary
Vascularization.
PMID- 28412252
TI - Replicative senescence promotes prothrombotic responses in endothelial cells:
Role of NADPH oxidase- and cyclooxygenase-derived oxidative stress.
AB - Endothelial senescence has been suggested to promote endothelial dysfunction in
age-related vascular disorders. This study evaluated the prothrombotic properties
of senescent endothelial cells (ECs) and the underlying mechanism. Serial
passaging from passage (P)1 to P4 (replicative senescence) of porcine coronary
artery ECs, or treatment of P1 ECs with the endothelial nitric oxide synthase
(eNOS) inhibitor L-NAME (premature senescence) induced acquisition of markers of
senescence including increased senescence-associated-beta-galactosidase (SA-beta
gal) activity and p53, p21, p16 expression. Approximately 55% of P3 cells were
senescent with a high level oxidative stress, and decreased eNOS-derived nitric
oxide (NO) formation associated with increased expression of NADPH oxidase
subunits (gp91phox, p47phox), cyclooxygenase (COX)-2 but not COX-1, and a
decreased eNOS expression leading to a reduced ability of ECs to inhibit platelet
aggregation. P3 cells also presented increased expression and activity of tissue
factor (TF), a key initiator of the coagulation cascade. Treatment of senesecent
cells with a NADPH oxidase inhibitor (VAS-2870) or by a COX inhibitor
(indomethacin) reduced oxidative stress, decreased TF activity and expression,
and reduced the expression of gp91phox, p47phox and COX-2 and restored the
ability of ECs to inhibit effectively platelet aggregation. Thus, replicative
endothelial senescence promotes a prothrombotic response involving the down
regulation of the protective NO pathway and the upregulation of the NADPH oxidase
and COXs-dependent oxidative stress pathway promoting TF expression and
activity.
PMID- 28412255
TI - Mini-Chimney Technique for Subclavian Artery Iatrogenic Bleeding.
PMID- 28412257
TI - Complete Healing of Spontaneous Coronary Artery Dissection Demonstrated by
Optical Coherence Tomography in a Young Postpartum Female Presenting With Acute
Coronary Syndrome.
PMID- 28412256
TI - Procedural and Long-Term Outcomes of Percutaneous Coronary Intervention for In
Stent Chronic Total Occlusion.
AB - OBJECTIVES: The study sought to investigate the long-term outcomes and predictors
of adverse events of percutaneous coronary intervention (PCI) for in-stent
chronic total occlusion (IS-CTO). BACKGROUND: IS-CTO PCI has traditionally been
associated with suboptimal success rates. METHODS: We performed a multicenter
registry of consecutive patients undergoing CTO PCI at 3 specialized centers.
Patients were divided in IS-CTO and de novo CTO. The primary endpoint (major
adverse cardiac events [MACE]) was a composite of cardiac death, target-vessel
myocardial infarction, and ischemia-driven target-vessel revascularization (TVR)
on follow-up. Independent predictors of MACE were sought with Cox regression.
RESULTS: We included 899 patients (n = 111 IS-CTO, n = 788 de novo CTO). Baseline
clinical and angiographic characteristics were balanced between the 2 groups.
Overall mean J-CTO (Japanese-Chronic Total Occlusion) score was 1.88 +/- 1.24 and
mean PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total
Occlusion Intervention-CTO) score was 1.04 +/- 0.88. Antegrade wire escalation
was used in 59.0% of IS-CTO and 48.1% of de novo CTO patients (p = 0.08).
Procedural success was achieved in 86.5% in both groups (p = 0.99). After a
median follow-up of 471 (interquartile range: 354 to 872) days, MACE were
observed in 20.8% versus 13.9% in IS-CTO versus de novo CTO (p = 0.07), driven by
TVR (16.7% vs. 9.4%; p = 0.03). IS-CTO was an independent predictor of MACE
(hazard ratio: 2.16; 95% confidence interval: 1.18 to 3.95; p = 0.01), together
with prior surgical revascularization and renal function, CTO PCI indicated for
acute coronary syndrome, number of diseased vessels, and PROGRESS-CTO score.
CONCLUSIONS: Procedural success was high and similar in patients with IS-CTO, as
compared with de novo CTO. However, IS-CTO was independently associated with MACE
(driven by TVR) on follow-up.
PMID- 28412258
TI - In-Stent CTO, Not as Easy as it Looks.
PMID- 28412259
TI - Right Aortic Arch With Left-Sided Arteria Lusoria: A Challenge for Radial
Interventionalists.
PMID- 28412260
TI - Is Oral Biopsy Associated With Change in Tobacco or Alcohol Use?
AB - PURPOSE: Tobacco and alcohol remain the predominant risk factors for oral cancer,
but the relation between having an oral biopsy and cessation of these risk
factors is unknown. Therefore, this investigation examined whether there might be
an association between oral biopsy and change in risk factor use. MATERIALS AND
METHODS: A survey was sent to a cohort consisting of a consecutive sample of
subjects identified in the University of North Carolina Oral Pathology database.
The predictor variable was oral biopsy diagnosis, with 3 levels consisting of
hyperkeratosis, dysplasia, or carcinoma. The outcome variable was change in risk
factor use, coded as "no change in usage," "decreased usage" or "quit." Other
study variables included age, gender, and race. The proportional odds model was
used to assess the effect of explanatory variables on change in use, and the P
value was set at .05. RESULTS: The response rate was 37.4% for a total sample of
605 subjects. White non-Hispanics composed 85% of respondents and women composed
49.5%, with no significant difference among diagnostic categories. The global
test for change in cigarette use was significant, with age contributing to
variability in behavioral change. Although not statistically significant, larger
percentages of patients with more severe diagnoses quit cigarettes and alcohol
following biopsy. The youngest respondents were 3.7 times more likely not to quit
before biopsy or to continue to smoke following biopsy (95% confidence interval,
1.98-6.91). CONCLUSION: The results of this study suggest that oral biopsy
provides an ideal opportunity to focus on risk factor cessation. Different
diagnoses provide objective data on which to base a discussion about
carcinogenesis and the roles played by the risk factors in this process.
Differences in risk factor cessation associated with demographics emphasize the
need for all clinicians to address cessation with all patients.
PMID- 28412261
TI - Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging-An Alternative to
Fine Needle Biopsy or Only an Adjunct Test in Preoperative Differential
Diagnostics of Malignant and Benign Parotid Tumors?
AB - PURPOSE: The role of dynamic magnetic resonance imaging (MRI) in the preoperative
differential diagnostics of parotid tumors is unclear. The aim of this study was
to compare the accuracy of dynamic MRI and routinely used fine needle biopsy
examination in the preoperative differentiation of malignant and benign parotid
tumors. MATERIALS AND METHODS: The study included 100 consecutive patients with
parotid tumors treated surgically at the authors' center. Accuracy of dynamic MRI
and fine needle biopsy examinations in the differential diagnostics of malignant
and benign lesions was verified against the gold standard (ie, final histologic
diagnosis). RESULTS: Based on histopathologic examination of surgical specimens,
19 tumors were eventually diagnosed as malignant lesions and 81 were diagnosed as
benign. Preoperative fine needle biopsy examination yielded 9 true positive, 70
true negative, 11 false positive, and 10 false negative results, which
corresponded to 47.4 and 86.4% sensitivity and specificity, respectively. The
most commonly established preoperative diagnosis for 10 tumors that were
misdiagnosed as benign based on examination of biopsy specimens was pleomorphic
adenoma (n = 10). Dynamic MRI examination yielded 17 true positive, 81 true
negative, 2 false negative, and 0 false positive results, which corresponded to
89.5% sensitivity and 100% specificity. CONCLUSIONS: These results suggest that
dynamic MRI is highly accurate in the detection of malignant parotid tumors.
However, taking into account the high cost and limited availability of this
examination, its logical application seems to be verification of preoperative
diagnoses in patients whose fine needle biopsy examination turned out to be
nondiagnostic or showed pleomorphic adenoma.
PMID- 28412262
TI - Surge of Surgeons? Surely!
PMID- 28412263
TI - Oculocardiac Reflex in an Orbital Fracture Without Entrapment.
AB - Large orbital fractures in older patients are infrequently associated with an
exaggerated oculocardiac reflex. This report describes the case of a patient in
his 40s with a large right orbital floor and medial wall fracture without
radiographic evidence of extraocular muscle compression or entrapment who
developed severe nausea and bradycardia with movement of his affected eye. The
patient exhibited bradycardia to 17 beats per minute during the initial
examination and was taken urgently to the operating room for reconstruction of
the right orbital floor and medial wall. Additional episodes of bradycardia
intraoperatively were responsive to glycopyrrolate. After the procedure, the
patient's pain was decreased, a normal range of motion was restored, and the
bradycardia and nausea resolved. An explanation for induction of the oculocardiac
reflex is considered in the absence of clinical or radiologic entrapment because
large orbital fractures are not often considered to induce this reflex.
PMID- 28412264
TI - ACS Fellowship for Single-Degree Oral and Maxillofacial Surgeons.
PMID- 28412265
TI - One-Stage Supramaximal Full-Thickness Wedge Resection of Vascular Lip Anomalies.
AB - PURPOSE: Vascular lip anomalies include infantile hemangiomas, venous
malformations, and arteriovenous malformations. Surgical management can be
complicated by alterations in horizontal length, vertical height, and lip
thickness from the underlying pathology. Additional reconstructive challenges
include preservation of oral continence, vermillion definition, and the sublabial
sulcus. This report describes a technique of supramaximal single-stage full
thickness wedge resection of these lesions. MATERIALS AND METHODS: A
retrospective study approved by the institutional review board of patients who
underwent full-thickness resection of vascular lip anomalies from December 2007
through February 2013 was performed. Patient demographics, final diagnosis,
preoperative treatment, examination findings (pre- and postoperative),
intraoperative management, and follow-up findings were reviewed. RESULTS:
Eighteen patients (9 female) with a mean age of 25 +/- 19.8 years (range, 3 to 70
yr) were identified. Underlying pathologies were arteriovenous malformation (6),
port wine stain with secondary soft tissue hypertrophy (6), capillary
malformation (1), venous malformation (3), and infantile hemangioma (2). Prior
treatments included embolization, lasers, surgical excision, steroids, and
propranolol; 8 patients were treatment naive. All patients underwent a single or
double pentagonal-shaped wedge resection of the involved upper or lower lip. An
average of 3.75 cm (41.7%; range, 20 to 70%) of horizontal lip length was
excised. Four patients required additional concomitant debulking of the
vermillion. No intraoperative complications were noted. Postoperatively, 1
patient developed wound dehiscence at 12 days and another had a midline
depression with mild oral incontinence. Follow-up averaged 1,074 days (range, 371
to 1,777 days) and patients and their parents reported a high degree of
satisfaction with the improvement in lip appearance and symmetry except for 1
patient who required further debulking. The sublabial sulcus and vermillion and
cutaneous definition were preserved in all cases. CONCLUSION: Despite the
traditional recommendation that no more than 30% of lip length be surgically
removed, vascular lip anomalies result in tissue hypertrophy, horizontal
elongation, ectropion labii, and tissue expansion that allow up to 70% of the lip
to be excised.
PMID- 28412266
TI - Hyperparathyroidism Diagnosed Due to Brown Tumors of the Jaw: A Case Report and
Literature Review.
AB - This report describes the case of a 42-year-old woman who consulted with a
maxillofacial specialist for pain and an exophytic lesion in the maxilla. Biopsy
examination disclosed a bone cyst with abundant giant cells, and head and neck
computed tomography was performed. A diagnosis of brown tumor in the maxilla and
mandible was made, and primary hyperparathyroidism (parathyroid adenoma) was
determined as the origin of the bone lesions. The patient underwent a left
superior parathyroidectomy, which resolved the hormonal disorder (as determined
by normal calcium and parathyroid hormone levels) and the brown tumors, which
appeared to have mineralized at 1-year follow-up computed tomography. Dental
implant rehabilitation was performed at the sites of the absent tumors. A
systematic review of articles published in the English-language medical
literature through the PubMed and Medline databases yielded 40 articles
(published from 1969 through 2016) on 45 cases of hyperparathyroidism associated
with the location of a brown tumor in the mandible or maxilla.
PMID- 28412267
TI - Pamidronate Disodium Leads to Bone Necrosis via Suppression of Wnt/beta-Catenin
Signaling in Human Bone Marrow Mesenchymal Stem Cells In Vitro.
AB - PURPOSE: Pamidronate disodium-associated bone necrosis is poorly understood at
the cellular and molecular levels. This study proposes a pathway leading to the
pamidronate disodium-mediated inhibition of osteogenic differentiation of human
bone marrow mesenchymal stem cells (BMMSCs) derived from the mandible in vitro.
MATERIALS AND METHODS: Primary human BMMSCs were isolated from the mandible and
marrow tissue. A proliferation assay was performed to determine the experimental
concentration of pamidronate disodium. Alkaline phosphatase (ALP) activity, ALP
staining, and Alizarin red S (ARS) staining were assessed after treatment with
pamidronate disodium (0, 0.1, 0.5, 1, 5, 10 MUg/mL). Quantitative real-time
polymerase chain reaction and western blotting specific for Wnt and beta-catenin
signaling genes or proteins were performed after treatment with pamidronate
disodium 0.5 MUg/mL. Wnt3a was used to observe the osteogenic differentiation of
BMMSCs during treatment with pamidronate disodium 0.5 MUg/mL. RESULTS: As
expected, pamidronate disodium 1, 5, and 10 MUg/ml were unfavorable for BMMSC
growth (P < .05), whereas 0.1 and 0.5 MUg/mL did not affect BMMSC growth (P >=
.05). BMMSCs treated with pamidronate disodium 0.5 MUg/mL had lower ALP activity,
ALP staining, and ARS staining (P < .05), and BMMSCs treated with low
concentrations (<0.5 MUg/mL) of pamidronate disodium had the same levels of ALP
activity, ALP staining, and ARS staining as the control (0 MUg/mL). Pamidronate
disodium 0.5 MUg/mL decreased the expression of genes and proteins involved in
Wnt and beta-catenin signaling. BMMSCs with Wnt3a and pamidronate disodium 0.5
MUg/mL had higher ALP activity, ALP staining, and ARS staining (P < .05).
CONCLUSIONS: Pamidronate disodium inhibited Wnt and beta-catenin signaling, which
controls osteogenic differentiation in BMMSCs. Wnt3a, a Wnt and beta-catenin
signaling activator, reversed the negative effects caused by pamidronate disodium
to salvage the osteogenic defect in BMMSCs.
PMID- 28412268
TI - How Is Third Molar Status Associated With the Occurrence of Mandibular Angle and
Condyle Fractures?
AB - PURPOSE: Third molars (M3s) have been hypothesized to be associated with the risk
of mandibular angle fracture and mandibular condylar fracture. The authors
systematically estimated the relative risk (RR) of M3 status for the development
of mandibular angle fracture and mandibular condylar fracture through a meta
analysis of cohort studies. MATERIALS AND METHODS: In this systematic review, the
PubMed, EMBASE, and Cochrane Library databases were searched from inception to
October 2016. The predictor of risk was the presence or absence of M3s. The
primary outcome was the RR of mandibular angle or condylar fracture. A fixed- or
a random-effects model was applied to evaluate the pooled risk estimates.
Sensitivity analysis also was performed to identify the potential sources of
heterogeneity. Publication bias was assessed by the Begg and Egger tests.
RESULTS: Overall, 13 retrospective cohort studies were included. Of these, 13
reported the association between M3s and mandibular angle fracture, and 5
reported the association with mandibular condylar fracture. Patients with M3s had
an increased risk of mandibular angle fractures (RR = 2.63; 95% confidence
interval [CI], 2.15-3.21) but a decreased risk of mandibular condylar fractures
(RR = 0.47; 95% CI, 0.25-0.86). Substantial heterogeneity in the risk estimates
was found. No evidence of publication bias was found. CONCLUSION: The present
meta-analysis provides further evidence associating the presence of M3s with an
increased risk of mandibular angle fractures and a simultaneously decreased risk
of mandibular condylar fracture. Because of potentially more serious
complications associated with condylar fracture, clinicians should carefully
consider the decision to remove M3s to decrease the risk of mandibular angle
fracture.
PMID- 28412269
TI - Towards an understanding of the isotype-specific functions of tubulin in neurons:
Technical advances in tubulin expression and purification.
AB - Microtubules are cytoskeletal filaments critical for determining the complex
morphology of neurons, as well as the basic architecture and organization of
mitosis in all eukaryotic cells. Microtubules in humans are composed of 8 alpha-
and 9 beta-tubulin isotypes, each of which is encoded by different members of a
multi-gene family. The expression pattern of tubulin isotypes, in addition to
isotype-specific post-translational modifications, is thought to be critical for
the morphogenesis of axons and dendrites. Recent studies revealed that several
neurodevelopmental disorders are caused by mutations of specific tubulin
isotypes, suggesting that each tubulin isotype has distinct functions. Therefore,
in vitro and in vivo functional analyses of tubulin isotypes are important to
understand the pathogenesis of developmental disorders. Likewise, analysis of
developmental disorders may clarify the function of different tubulin isotypes.
In this respect, both the preparation of specific tubulin isotypes and of
specific mutant tubulin proteins is critical to understanding the function of
tubulin. In the last 20 years, various methods have been developed to study
functional differences between tubulin isotypes and the functional defects caused
by tubulin mutations. These technical achievements have been discussed in this
review. The function of tubulin/microtubules in neuronal morphogenesis as
revealed through these techniques has also been described.
PMID- 28412270
TI - How Surgeons Conceptualize Talent: A Qualitative Study Using Sport Science as a
Lens.
AB - OBJECTIVES: Debates prevail regarding the definition of surgical talent, and how
individuals with the potential to become talented surgeons can be identified and
developed. However, over the past 30 years, talent has been studied extensively
in other domains. The objectives of this study is to explore notions of talent in
surgery and sport in order to investigate if the field of surgical education can
benefit from expanding its view on talented performances. Therefore, this study
aims to use the sport literature as a lens when exploring how surgeons
conceptualize and define talent. DESIGN: Semi-structured interviews were
conducted with a sample of 11 consultant surgeons from multiple specialties. We
used constructivist grounded theory principles to explore talent in surgery.
Ongoing data analysis refined the theoretical framework and iteratively informed
data collection. Themes were identified iteratively using constant comparison.
SETTING: The setting included 8 separate hospitals across Canada and Denmark.
PARTICIPANTS: A total of 11 consultant surgeons from 6 different surgical
subspecialties (urology, orthopedic surgery, colorectal surgery, general surgery,
vascular surgery, head & neck surgery) were included. RESULTS: We identified
three key elements for conceptualizing surgical talent: (1) Individual skills
makes the surgical prospect "good", (2) a mixture of skills gives the surgical
prospect the potential to become talented, and (3) becoming talented may rely on
the fit between person and environment. CONCLUSION: We embarked on a study aimed
at understanding talent in surgery. Talent is a difficult construct to agree on.
Whether in medicine or sports, debates about talent will continue to persist, as
we all perceive talent differently. While we heard different opinions, three key
ideas summarize our participants' discussions regarding surgical talent. These
findings resonate with the holistic ecological approach from sport science and
hence highlight the limits of a reductionist approach while favoring the
individual-environment system as the minimal ontology for describing talented
performances.
PMID- 28412271
TI - Impact of a new distal attachment on colonoscopy performance in an academic
screening center.
AB - BACKGROUND AND AIMS: Distal attachments placed on the colonoscope tip may
positively affect performance by assisting insertion and polyp detection. The
original Endocuff (ARC Medical Design, Leeds, United Kingdom) appears to improve
adenoma detection rate (ADR), but no data assess the performance of the second
generation Endocuff Vision. METHODS: A pilot service evaluation study (April 2013
to September 2014) was conducted on patients with positive fecal occult blood
tests within the National Bowel Cancer Programme during 3 consecutive periods:
precuff/no device used, during-cuff/device used, and postcuff/no device used.
During the middle period the use of the Endocuff Vision by the 4 screening
accredited colonoscopists was discretional (nonrandomized design). Data were
analyzed using pairwise comparisons during the 3 designated periods to examine
key performance indicators: adenoma detection, procedural time, sedation
requirements, and patient comfort. RESULTS: Four hundred ten complete
colonoscopies were performed (137 precuff, 136 cuff, and 137 postcuff period).
Overall, there was a notable increase in the mean ADR of 16% (P < .03) and in the
mean number adenoma per procedure (MAP) of 83% (P = .007) from precuff to cuff
period. The mean cecal intubation time was statistically lower during the cuff
period (7 minutes) in relation to the precuff period (8 minutes; reduction of
12.5%, P = .002) and the postcuff period (9 minutes; increase of 28.6%, P =
.002). The mean negative colonoscopy withdrawal time was also significantly lower
during the cuff period (8 minutes, 30 seconds) when compared with the precuff (12
minutes) or postcuff period (9 minutes, 45 seconds; P <= .001). Multivariate
regression analysis showed that the use of the Endocuff Vision was not associated
with sedation requirements or patient discomfort scores. No adverse events were
reported from the use of the Endocuff Vision, although it was electively removed
in 6 patients where severe sigmoid colon diverticulosis was encountered and 2
patients because of discomfort during anal insertion. CONCLUSIONS: In this pilot
service evaluation study, the use of the Endocuff Vision appears to be associated
with an improvement in overall colonoscopy operator performance. We found
increased ADR and MAP as well as decreased time for colonoscope insertion and
withdrawal time with no increase in sedation requirements or patient discomfort.
PMID- 28412272
TI - Use of ceftolozane/tazobactam as salvage therapy for infections due to
extensively drug-resistant Pseudomonas aeruginosa.
PMID- 28412273
TI - Efficient inhibition of influenza A viral replication in cells by deoxyribozymes
delivered by nanocomposites.
AB - Nucleic-acid-based drugs are a promising class of novel therapeutics; however,
their use in medicine is widely limited because of insufficient delivery into
cells. This article proposes a new delivery strategy of nucleic acid fragments
into cells as components of TiO2-based nanocomposites. For the first time,
unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles
precovered with polylysine (TiO2*PL) with the formation of (TiO2*PL)*Dz
nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain
their ability to cleave the RNA target in a cell-free system with the same
selectivity as unbound Dz molecules. It was shown by confocal laser microscopy
that the fluorescein-labelled (TiO2*PL)*DzFlu nanocomposites penetrate into
eukaryotic cells, where DzFlu is internalized in the cytoplasm and predominantly
in nuclei. Delivery of deoxyribozymes into cells in the proposed nanocomposites
permits very efficient interactions with RNA targets inside cells. This was
demonstrated by an example of inhibition of H5N1 influenza A virus replication
(inhibition by a factor of ca. 3000). This effect was one order of magnitude
higher than with using lipofectamine as the transfection agent. The proposed
(TiO2*PL)*Dz nanocomposites demonstrated high antiviral activity and are thus
potent as nucleic-acid-based drugs.
PMID- 28412274
TI - Pharmacokinetics of linezolid in critically ill patients: impact of continuous
venovenous haemofiltration.
PMID- 28412276
TI - The influence of hypertension on daytime sleepiness in obstructive sleep apnea.
AB - Daytime sleepiness is a common symptom among hypertensive patients. The aim of
this study was to determine subjective sleepiness assessed by Epworth Sleepiness
Scale (ESS) and to asses sleep architecture in 304 patients with arterial
hypertension. All patients underwent a standardized diagnostic overnight,
polysomnography. The control group consisted of 67 normotensives. The
hypertensive patients had a decreased sleep efficiency, mean and minimum oxygen
saturation levels, and increased apnea/hypopnea index and oxygen desaturation
index compared with normotensive patients. The lower ratio of N3 sleep, higher of
N2 sleep, and decreased sleep efficiency was observed in hypertensives without
obstructive sleep apnea (OSA). In the moderate to severe OSA groups, the total
ESS score was significantly lower in hypertensives compared with normotensives.
The ESS scores decreased with age in hypertensives, but not in normotensives. The
study showed that ESS total score is lower in hypertensives than in normotensives
with OSA, making the OSA more difficult to suspect. Thus, the low ESS score in
hypertensives should not discourage further evaluation.
PMID- 28412275
TI - Achieving the BpTRUth: emergency department hypertension screening and the
Centers for Medicare & Medicaid Services quality measure.
AB - In 2012, the Centers for Medicare & Medicaid Services (CMS) instituted a
Physician Quality Reporting System measure for screening and referring patients
with elevated blood pressure (BP). The aims of this study were to (1) assess the
reliability of ED triage BP as a metric to establish when the CMS threshold
(>=120/80 mm Hg), and other clinically relevant BP thresholds (>=140/90 and
>=160/100 mm Hg) have been met, using BP measured with a highly accurate device
(BpTRU) in the emergency department as the gold standard; and (2) determine
whether correct identification varies by gender, race, or triage acuity. Using
the BpTRU, we calculated the proportion of patients whose triage BP accurately
indicated a need for further referral and treatment for hypertension according to
three suggested BP thresholds (>=120/80, >=140/90, and >=160/100 mm Hg). Of 354
patients, the median age was 39 years, 48.9% were women, and 66.4% were White. At
the three suggested BP thresholds (>=120/80, >=140/90, and >=160/100 mm Hg),
66.1%, 74.0%, and 88.8% of patients were confirmed to meet the CMS threshold,
respectively. There were no differences by gender, race, or triage acuity.
Emergency department triage BP would reliably identify elevated BP using the CMS
threshold in up to two-thirds of those without known hypertension.
PMID- 28412277
TI - The association of endothelial function and tone by digital arterial tonometry
with MRI left ventricular mass in African Americans: the Jackson Heart Study.
AB - Peripheral vascular endothelial dysfunction assessed by digital peripheral
arterial tonometry (PAT) has been associated with risk for adverse cardiovascular
events. We examined the relations of peripheral microvascular dysfunction and
left ventricular mass in a community-based cohort of African Americans. We
examined participants of the Jackson Heart Study who had PAT and cardiac magnetic
resonance imaging evaluations between 2007 and 2013. Consistent with pertinent
literature, left ventricular mass index (LVMI) was adjusted for body size by
indexing to height2.7. Pearson's correlation and general linear regression
analyses were used to relate reactive hyperemia index, baseline pulse amplitude
(BPA), and augmentation index (markers of microvascular vasodilator function,
baseline vascular pulsatility, and relative wave reflection, respectively) to
LVMI after adjusting for traditional cardiovascular risk factors. A total of 440
participants (mean age 59 +/- 10 years, 60% women) were included. Age- and sex
adjusted Pearson's correlation analysis suggested that natural log transformed
LVMI was negatively correlated with reactive hyperemia index (coefficient:
0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P <
.001). In multivariable analyses, higher loge LVMI was associated with higher BPA
(beta: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes,
hypertension, ratio of total cholesterol and high-density lipoprotein
cholesterol, smoking, and history of cardiovascular disease. In a community-based
sample of African Americans, higher baseline pulsatility measured by PAT was
associated with higher LVMI by cardiac magnetic resonance imaging after adjusting
for traditional risk factors.
PMID- 28412278
TI - Disruption of glutamate neurotransmitter transmission is modulated by SNAP-25 in
benzo[a]pyrene-induced neurotoxic effects.
AB - Benzo[a]pyrene (B[a]P), a ubiquitous chemical contaminant in the environment, is
a well-established neurotoxicant to human. However, the molecular mechanisms for
B[a]P neurotoxicity are still unclear. In the present study, after treating
Sprague-Dawley rats with 0.02, 0.2 and 2.0mg/kg/day B[a]P for 7 weeks [from
postnatal day (PND) 5 to PND54], our results showed that B[a]P exposure caused a
significant deficits in learning and memory function. By using U87 cells as in
vitro model, the significant cytotoxicity and the induction of apoptosis caused
by B[a]P were further verified. More importantly, we demonstrated for the first
time that B[a]P exposure caused the disruption of glutamate (Glu)
neurotransmitter transmission by decreasing the level of Glu, reducing the
expression of Glu receptors (GluR1 and GluR2), enhancing the level of SNAP-25,
widening the synaptic cleft, and ultimately producing the neurotoxic effects in
both cells and animals. Our results will provide novel evidence to reveal the
possible role of SNAP-25 in B[a]P-induced neurotoxicity and may be helpful for
searching the potential strategy for the prevention measures against B[a]P
neurotoxicity.
PMID- 28412280
TI - Evaluation of sample preparation protocols for spider venom profiling by MALDI
TOF MS.
AB - Spider venoms are highly complex mixtures containing biologically active
substances with potential for use in biotechnology or pharmacology.
Fingerprinting of venoms by Matrix-Assisted Laser Desorption-Ionization - Time of
Flight Mass Spectrometry (MALDI-TOF MS) is a thriving technology, enabling the
rapid detection of peptide/protein components that can provide comparative
information. In this study, we evaluated the effects of sample preparation
procedures on MALDI-TOF mass spectral quality to establish a protocol providing
the most reliable analytical outputs. We adopted initial sample preparation
conditions from studies already published in this field. Three different MALDI
matrixes, three matrix solvents, two sample deposition methods, and different
acid concentrations were tested. As a model sample, venom from Brachypelma
albopilosa was used. The mass spectra were evaluated on the basis of absolute and
relative signal intensities, and signal resolution. By conducting three series of
analyses at three weekly intervals, the reproducibility of the mass spectra were
assessed as a crucial factor in the selection for optimum conditions. A sample
preparation protocol based on the use of an HCCA matrix dissolved in 50%
acetonitrile with 2.5% TFA deposited onto the target by the dried-droplet method
was found to provide the best results in terms of information yield and
repeatability. We propose that this protocol should be followed as a standard
procedure, enabling the comparative assessment of MALDI-TOF MS spider venom
fingerprints.
PMID- 28412279
TI - Cancer biology and Mr. Darwin.
PMID- 28412281
TI - Assessing the exploratory and anxiety-related behaviors of mice. Do different
caging systems affect the outcome of behavioral tests?
AB - Ample studies have shown that housing can affect the health, welfare and behavior
of mice and therefore, the outcomes of certain experiments. The aim of this study
was to investigate if three widely used housing systems, Open Top Cages (OTC),
Motor Free Ventilated Cages (MFVC) and Individually Ventilated Cages (IVC) may
affect exploratory and anxiety-related behaviors in mice. Subjects were 8week-old
male C57Bl/6J mice (n=36) divided into three groups, OTC, IVC and MFVC groups,
respectively. The experimental procedure consisted of two behavioral tests: the
open field and the elevated plus maze test. Although there were no differences in
the open field test, the results from the elevated plus maze showed that animals
housed in the MFVCs exhibited increased exploratory and less anxiety-like
behavior. It is concluded that the different caging systems may have an impact on
the outcome of behavioral tests used to assess exploratory and anxiety like
behavior in mice. Therefore, it is essential to take into consideration housing
conditions when reporting, analyzing, and/or systematically reviewing the results
of behavioral testing in mice.
PMID- 28412282
TI - Physiological reactivity to spontaneously occurring seizure activity in dogs with
epilepsy and their carers.
AB - There is a complex bidirectional relationship between stress and epilepsy.
Stressful stimuli and subsequent cortisol release act as a trigger for seizure
activity in some individuals with epilepsy, and seizure activity itself may act
as a stressor to the affected individual. Epilepsy is the most common chronic
neurological condition in domestic dogs and requires chronic management by their
human carers, impacting upon the quality of life of both dog and carer. Seizures
occur unpredictably and may be stressful for carers to witness and manage. In the
present study we investigated the role of seizure activity as a stressor,
measuring the effect of spontaneously occurring seizure activity in dogs with
epilepsy upon their own cortisol levels and that of their carers. Furthermore, we
tested whether individual differences in HPA reactivity were associated with
owner personality characteristics and the quality of the dog-carer relationship.
Saliva samples were obtained from sixteen dog-carer dyads in the home setting 20
and 40minute post-seizure, and at time-matched points on the following (non
seizure) day. Significant differences in cortisol levels were found in dogs at
40minute post-seizure (265.1% increase), and at 20minute post-seizure in their
carers (40.5% increase). No associations were found between cortisol reactivity
and the strength of the dog-carer bond. Carers with higher neuroticism scores
exhibited higher cortisol levels at both post-seizure sampling points. As there
was a gender bias in the carer sample (15/16 were female), and there are known
sex differences in cortisol reactivity in response to psychological stress, the
conclusions of this study may be limited to female carers. These findings are the
first to objectively demonstrate the acutely stressful effects of seizures in
dogs with epilepsy and their carers.
PMID- 28412283
TI - Complement factor C4 activation in patients with hereditary angioedema.
AB - OBJECTIVES: Low complement factor C4 is usually considered a valuable screening
tool for patients with the potentially life-threatening hereditary angioedema
with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients
with C1-INH-HAE presenting with normal C4 levels. This means, that C1-INH-HAE may
potentially be overlooked, if screening is performed only by measurement of C4.
It has been suggested that measurement of C4 activation products is better suited
to avoid false negative results. Our aim was to investigate whether total
antigenic C4 or non-functional C4c is a better measure of the increased C4
activation in C1-INH-HAE patients. DESIGN AND METHODS: Two different monoclonal
antibodies (mAb) to human C4 were produced: one had specificity for the beta
chain of C4 and would thus react with both functional and non-functional C4, and
the other was developed against the factor I cleavage site on the alpha3-domain
of C4 and was thus specific for activated, non-functional C4c. With these mAb we
investigated plasma from 19 Danish C1-INH-HAE patients in three different enzyme
linked immunosorbent assays (ELISAs): a total antigenic C4 assay, a functional C4
assay and an assay measuring non-functional C4c. RESULTS: The amount of total
antigenic C4 varied considerably between patients and 2 patients had total
antigenic C4 levels in the normal area. Functional C4 was low in all C1-INH-HAE
patients. A C4c/C4 ratio showed that around half the C4 measured in patients was
non-functional and captured all C1-INH-HAE patients. CONCLUSIONS: This study
shows that the C4c/C4 ratio seems to be a better diagnostic measure than total
antigenic C4 alone. Our findings underline that screening with total antigenic C4
implies a risk of overlooking C1-INH-HAE patients.
PMID- 28412284
TI - Effects of preanalytical factors on hemoglobin measurement: A comparison of two
HemoCue(r) point-of-care analyzers.
AB - BACKGROUND: In field studies, hemoglobin (Hb) is often measured using a battery
operated, portable HemoCue(r) hemoglobinometer. METHODS: We compared the
performance of 2 HemoCue(r) models (Hb-201+ and Hb-301) and investigated effects
of preanalytical factors on Hb results by simulating unfavorable field
conditions. RESULTS: The Hb-301 produced 2.6% higher results compared to the Hb
201+. Hb had to be measured within 1min of filling the Hb-301 cuvette to avoid
artificially elevated concentrations (1.3% per min). The Hb-301 cuvettes
withstood elevated temperature (37 degrees C) and humidity (72%) for 3weeks,
while the Hb-201+ cuvettes degraded within 10min under those conditions. Both
cuvette types withstood elevated temperature for 3weeks. Properly-collected
venous and capillary blood produced comparable results. Pooled capillary blood
produced comparable results to the second and third but not the fourth drop of
blood (3.3% lower). Blood could be stored for <=4days at 10-30 degrees C before
Hb-201+ measurement, but only for 1day at 10-23 degrees C before Hb-301
measurement (<=1% change in Hb). CONCLUSIONS: Higher Hb results obtained with the
Hb-301 may influence the interpretation of anemia prevalence in health surveys.
While the Hb-301 performed better in high humidity conditions, the Hb-201+
provided more user flexibility regarding delayed Hb reading.
PMID- 28412285
TI - Middle East respiratory syndrome coronavirus vaccines: current status and novel
approaches.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe
respiratory infection in humans, specifically the elderly and people with
comorbidities. The re-emergence of lethal coronaviruses calls for international
collaboration to produce coronavirus vaccines, which are still lacking to date.
Ongoing efforts to develop MERS-CoV vaccines should consider the different target
populations (dromedary camels and humans) and the correlates of protection.
Extending on our current knowledge of MERS, vaccination of dromedary camels to
induce mucosal immunity could be a promising approach to diminish MERS-CoV
transmission to humans. In addition, it is equally important to develop vaccines
for humans that induce broader reactivity against various coronaviruses to be
prepared for a potential next CoV outbreak.
PMID- 28412286
TI - Beneficial effects of glutathione supplementation during vitrification of mouse
oocytes at the germinal vesicle stage on their preimplantation development
following maturation and fertilization in vitro.
AB - Oocyte cryopreservation is imperative for assisted reproductive technologies
(ART). Although cryopreservation of oocytes at the Metaphase II has been widely
used, immature oocytes at the germinal vesicle stage (GV-oocytes) need to be
cryopreserved in certain situations such as cancer patients; however, the success
rate of embryonic development from the GV-oocytes remains low largely due to the
requirement for in vitro maturation (IVM). Our aim was to investigate the effects
of glutathione (GSH) supplementation during vitrification and warming of mouse GV
oocytes on the preservation of developmental competence. GV-oocytes within
cumulus oocyte complexes (COCs) were collected from C57BL/6J (B6) and (B6.DBA)F1
mouse strains and subjected to vitrification and warming, followed by IVM. The
vitrification, warming or IVM medium was supplemented with GSH at 0-4.0 mM. In
vitro matured oocytes were then fertilized in vitro and cultured in KSOMaa up to
4 days. The first cleavage and blastocyst development were evaluated
morphologically, and their rates were statistically analysed by one-way ANOVA
followed by Tukey's multiple comparisons test. The difference was considered
significant at P < 0.05. The results showed that GSH supplementation in the IVM
medium exhibited no or rather inhibitory effects on the first cleavage or
blastocyst development in both mouse strains except that 1.0 mM GSH increased the
blastocyst development rate in B6. By contrast, 1 mM GSH supplementation during
vitrification and warming increased the blastocyst development rate in both mouse
strains, more efficiently in B6 than (B6.DBA)F1. In conclusion, GSH
supplementation during vitrification and warming of GV-oocytes protects the
oocytes from freezing-inflicted loss of developmental competence.
PMID- 28412288
TI - Adult T-type lymphoblastic lymphoma: Treatment advances and prognostic
indicators.
AB - T-cell lymphoblastic lymphoma (T-LBL) is a rare, aggressive neoplasm of precursor
T cells that occurs mostly in adolescents and young adults. In this review, we
describe the treatment of adult T-LBL with a focus on recent advances using
pediatric-inspired acute lymphoblastic leukemia regimens, which have greatly
improved outcome. We also discuss the development of prognostic indicators for T
LBL, especially oncogenetic factors, that can identify patients at higher risk of
relapse and may help further extend T-LBL patient survival. Pediatric-inspired
acute lymphoblastic leukemia regimens have the potential to become the treatment
of choice for adult T-LBL, and they might also reduce the need for other
longstanding T-LBL interventions, particularly mediastinal irradiation and stem
cell transplantation.
PMID- 28412287
TI - Changes in rat respiratory system produced by exposure to exhaust gases of
combustion of glycerol.
AB - The combustion of residual glycerol to generate heat in industrial processes has
been suggested as a cost-effective solution for disposal of this environmental
liability. Thus, we investigated the effects of exposure to the exhaust gases of
glycerol combustion in the rat respiratory system. We used 2 rats groups, one
exposed to the exhaust gases from glycerol combustion (Glycerol), and the other
exposed to ambient air (Control). Exposure occurred 5h a day, 5days a week for 13
weeks. We observed statistically changes in all parameters of respiratory system
mechanics in vivo. This results was supported by histological analysis and
morphometric data, confirming narrower airways and lung parenchimal changes.
Variables related to airway resistance (DeltaRN) and elastic properties of the
tissue (DeltaH), increased after challenge with methacholine. Finally, analysis
of lung tissue micromechanics showed statistically increases in all parameters
(R, E and hysteresivity). In conclusion, exhaust gases from glycerol combustion
were harmful to the respiratory system.
PMID- 28412291
TI - Reply to: "Negotiating better discounts for DAA therapy is critical to achieve
HCV elimination by 2030".
PMID- 28412290
TI - Lack of decline in hepatitis C virus incidence among HIV-positive men who have
sex with men during 1990-2014.
AB - BACKGROUND & AIMS: Hepatitis C virus (HCV) incidence among HIV-positive men who
have sex with men (MSM) has increased since 2000, although there are regional
differences. We aimed to 1) estimate trends in HCV incidence among HIV-positive
MSM, 2) assess the association between incidence and geographical region, age and
HIV-related measurements and, 3) assess temporal changes from HIV seroconversion
to HCV infection. METHODS: Data was used from MSM with well-estimated dates of
HIV seroconversion from the CASCADE Collaboration (1990-2014). Smoothly varying
trends in HCV incidence over time were allowed, using restricted cubic splines.
The association of calendar year, age, CD4 count (lagged), HIV RNA (lagged),
geographical region and HIV infection stage (recent vs. chronic) with HCV
incidence were assessed using Poisson regression. RESULTS: Of 5,941 MSM, 337
acquired HCV during follow-up. HCV incidence significantly increased from
0.7/1,000 person-years in 1990 to 18/1,000 person-years in 2014. Recent calendar
years, younger age, recent HIV infection and higher HIV RNA levels were
significantly associated with HCV incidence, while CD4 count was not. Trends
differed by geographical region; while incidence appeared to have stabilized in
Western Europe and remained stable in Southern Europe, it continued to increase
in Northern Europe in recent years. Time from HIV to HCV infection significantly
decreased over time (p<0.001). CONCLUSIONS: HCV has continued to spread among HIV
positive MSM in recent years, but trends differ by geographical region.
Interventions to decrease the risk of HCV acquisition and increase early
diagnosis are warranted. LAY SUMMARY: Hepatitis C virus infection continues to
spread among HIV-positive men who have sex with men, especially among younger
individuals. However, trends seem to differ by European region in recent years.
Furthermore, men who have sex with men with a higher HIV RNA load were more
likely to get infected with the hepatitis C virus. During recent HIV infection,
MSM appear to be at higher risk of acquiring hepatitis C.
PMID- 28412289
TI - Structural studies of the endogenous spliceosome - The supraspliceosome.
AB - Pre-mRNA splicing is executed in mammalian cell nuclei within a huge (21MDa) and
highly dynamic molecular machine - the supraspliceosome - that individually
package pre-mRNA transcripts of different sizes and number of introns into
complexes of a unique structure, indicating their universal nature. Detailed
structural analysis of this huge and complex structure requires a stepwise
approach using hybrid methods. Structural studies of the supraspliceosome by room
temperature electron tomography, cryo-electron tomography, and scanning
transmission electron microscope mass measurements revealed that it is composed
of four native spliceosomes, each resembling an in vitro assembled spliceosome,
which are connected by the pre-mRNA. It also elucidated the arrangement of the
native spliceosomes within the intact supraspliceosome. Native spliceosomes and
supraspliceosomes contain all five spliceosomal U snRNPs together with other
splicing factors, and are active in splicing. The structure of the native
spliceosome, at a resolution of 20A, was determined by cryo-electron microscopy,
and a unique spatial arrangement of the spliceosomal U snRNPs within the native
spliceosome emerged from in silico studies. The supraspliceosome also harbor
components for all pre-mRNA processing activities. Thus the supraspliceosome -
the endogenous spliceosome - is a stand-alone complete macromolecular machine
capable of performing splicing, alternative splicing, and encompass all nuclear
pre-mRNA processing activities that the pre-mRNA has to undergo before it can
exit from the nucleus to the cytoplasm to encode for protein. Further high
resolution cryo-electron microscopy studies of the endogenous spliceosome are
required to decipher the regulation of alternative splicing, and elucidate the
network of processing activities within it.
PMID- 28412292
TI - HLA-Bw4 80(T) and multiple HLA-Bw4 copies combined with KIR3DL1 associate with
spontaneous clearance of HCV infection in people who inject drugs.
AB - BACKGROUND & AIMS: Natural killer (NK) cell function is regulated by inhibitory
and activating receptors including killer cell immunoglobulin-like receptors
(KIRs). Here, we analyzed the impact of different KIR/KIR-ligand genotypes on the
outcome of hepatitis C virus (HCV) infection in people who inject drugs (PWID).
METHODS: KIR/KIR-ligand genotypes associated with spontaneous clearance of HCV
infection were identified in a cohort of PWID from Germany (n=266) and further
validated in a second anti-HCV positive cohort of PWID recruited in North America
(n=342). NK cells of PWID and healthy donors were functionally characterized
according to their KIR/KIR-ligand genotype by flow cytometry. RESULTS:
Multivariate logistic regression analysis revealed that KIR3DL1/HLA-Bw4 80(T) was
associated with spontaneous clearance of HCV infection in PWID, which was
confirmed in the PWID cohort from North America. Compared with PWID with
detectable HCV RNA, the frequency of individuals with multiple HLA-Bw4 alleles
was significantly higher in anti-HCV positive PWID with resolved HCV infection
(29.7% vs. 15.2%; p=0.0229) and in anti-HCV seronegative PWID (39.2%; p=0.0006).
KIR3DL1+ NK cells from HLA-Bw4 80(T)-positive PWID showed superior functionality
compared to HLA-Bw4 80(I)-positive PWID. This differential impact was not
observed in healthy donors; however, the HLA-Bw4 copy number strongly correlated
with the functionality of KIR3DL1+ NK cells. CONCLUSIONS: HLA-Bw4-80(T) and
multiple HLA-Bw4 copies in combination with KIR3DL1 are associated with
protection against chronic hepatitis C in PWID by distinct mechanisms. Better
licensing of KIR3DL1+ NK cells in the presence of multiple HLA-Bw4 copies is
beneficial prior to seroconversion whereas HLA-Bw4 80(T) may be beneficial during
acute hepatitis C. Lay summary: Natural killer (NK) cells are part of the innate
immune system and are regulated by a complex network of activating and inhibiting
receptors. The regulating receptor-ligand pairs of an individual are genetically
determined. Here, we identified a particular set of ligand and receptor genes
that are associated with better functionality of NK cells and better outcome upon
exposure to HCV in a high-risk group.
PMID- 28412293
TI - Glecaprevir and pibrentasvir yield high response rates in patients with HCV
genotype 1-6 without cirrhosis.
AB - BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy that is highly efficacious,
pangenotypic, with a high barrier to resistance and short treatment duration is
desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir
(ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor)
were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.
METHODS: SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose
ranging trials including patients with chronic HCV genotype 1-6 infection who
were either previously untreated or treated with pegylated interferon plus
ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying
doses with or without ribavirin for 8 or 12weeks. The primary efficacy endpoint
was the percentage of patients with a sustained virologic response at post
treatment week 12 (SVR12). RESULTS: Of the 449 patients who received varying
doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1,
2, 3, and 4-6 infection, respectively. Twelve-week treatment achieved SVR12 in 97
100%, 96-100%, 83-94%, and 100% in genotypes 1, 2, 3, and 4-6, respectively.
Eight-week treatment with 300mg glecaprevir plus 120mg pibrentasvir in genotype 1
, 2-, or 3-infected patients yielded 97-98% SVR12 with no virologic failures.
Three (0.7%) patients discontinued treatment due to adverse events; most events
were mild (grade 1) in severity. No post-nadir alanine aminotransferase
elevations were observed. CONCLUSIONS: Glecaprevir plus pibrentasvir was well
tolerated and achieved high sustained virologic response rates in HCV genotypes 1
6-infected patients without cirrhosis following 8- or 12-week treatment
durations. LAY SUMMARY: The combination of direct-acting antivirals glecaprevir
and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV
genotype 1-6 infection. This article describes results from two phase II trials
investigating a range of doses at treatment durations of 8 or 12weeks in 449
patients without cirrhosis. Efficacy of the optimal dose, as determined by rates
of sustained virologic response at post-treatment week 12, ranged from 92%-100%;
treatment was well tolerated and significant laboratory abnormalities were rare.
CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT02243280 and
NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280,
http://www.clinicaltrials.gov/show/NCT01939197.
PMID- 28412294
TI - Visualization of hepatitis E virus RNA and proteins in the human liver.
AB - BACKGROUND & AIMS: Although hepatitis E constitutes a substantial disease burden
worldwide, surprisingly little is known about the localization of hepatitis E
virus (HEV) in the human liver. We therefore aimed to visualize HEV RNA and
proteins in situ. METHODS: A panel of 12 different antibodies against HEV open
reading frame (ORF) 1-3 proteins was evaluated for immunohistochemistry (IHC) and
two probes for in situ hybridization (ISH) in formalin-fixed, paraffin-embedded
(FFPE) HuH7 cells transfected with HEV ORF1-3 expression vectors. IHC (and partly
ISH) were then applied to Hep293TT cells replicating infectious HEV and liver
specimens from patients with hepatitis E (n=20) and controls (n=134). RESULTS:
Whereas ORF1-3 proteins were all detectable in transfected, HEV protein
expressing cells, only ORF2 and 3 proteins were traceable in cells replicating
infectious HEV. Only the ORF2-encoded capsid protein was also unequivocally
detectable in liver specimens from patients with hepatitis E. IHC for ORF2
protein revealed a patchy expression in individual or grouped hepatocytes,
generally stronger in chronic compared to acute hepatitis. Besides cytoplasmic
and canalicular, ORF2 protein also displayed a hitherto unknown nuclear
localization. Positivity for ORF2 protein in defined areas correlated with HEV
RNA detection by ISH. IHC was specific and comparably sensitive as PCR for HEV
RNA. CONCLUSIONS: ORF2 protein can be reliably visualized in the liver of
patients with hepatitis E, allowing for sensitive and specific detection of HEV
in FFPE samples. Its variable subcellular distribution in individual hepatocytes
of the same liver suggests a redistribution of ORF2 protein during infection and
interaction with nuclear components. LAY SUMMARY: The open reading frame (ORF) 2
protein can be used to visualize the hepatitis E virus (HEV) in the human liver.
This enabled us to discover a hitherto unknown localization of the HEV ORF2
protein in the nucleus of hepatocytes and to develop a test for rapid
histopathologic diagnosis of hepatitis E, the most common cause of acute
hepatitis worldwide.
PMID- 28412295
TI - Evidence for a role of genetics in alcoholic hepatitis: Data from the STOPAH
randomized controlled trial.
PMID- 28412297
TI - Dysferlinopathy Promotes an Intramuscle Expansion of Macrophages with a Cyto
Destructive Phenotype.
AB - Dysferlinopathies are a group of muscular dystrophies resulting from a genetic
deficiency in Dysf. Macrophages, highly plastic cells that mediate tissue repair
and destruction, are prominent within dystrophic skeletal muscles of
dysferlinopathy patients. We hypothesized that Dysf-deficient muscle promotes
recruitment, proliferation, and skewing of macrophages toward a cyto-destructive
phenotype in dysferlinopathy. To track macrophage dynamics in dysferlinopathy, we
adoptively transferred enhanced green fluorescent protein-labeled monocytes into
Dysf-deficient BLA/J mice with age-related (2 to 10 months) muscle disease and
Dysf-intact (C57BL/6 [B6]) mice. We detected an age- and disease-related increase
in monocyte recruitment into Dysf-deficient muscles. Moreover, macrophages
recruited into muscle proliferated locally and were skewed toward a cyto
destructive phenotype. By comparing Dysf-deficient and -intact monocytes, our
data showed that Dysf in muscle, but not in macrophages, mediate intramuscle
macrophage recruitment and proliferation. To further elucidate macrophage
mechanisms related to dysferlinopathy, we investigated in vitro macrophage
myogenic cell interactions and found that Dysf-deficient muscle i) promotes
macrophage proliferation, ii) skews macrophages toward a cyto-destructive
phenotype, and iii) is more vulnerable to macrophage-mediated apoptosis. Taken
together, our data suggest that the loss of Dysf expression in muscle, not
macrophages, promotes the intramuscle expansion of cyto-destructive macrophages
likely to contribute to dysferlinopathy. Identifying pathways within the Dysf
deficient muscle milieu that regulate cyto-destructive macrophages will
potentially uncover therapeutic strategies for dysferlinopathies.
PMID- 28412296
TI - Impact of higher-order heme degradation products on hepatic function and
hemodynamics.
AB - BACKGROUND & AIMS: Biliverdin and bilirubin were previously considered end
products of heme catabolism; now, however, there is evidence for further
degradation to diverse bioactive products. Z-BOX A and Z-BOX B arise upon
oxidation with unknown implications for hepatocellular function and integrity. We
studied the impact of Z-BOX A and B on hepatic functions and explored their
alterations in health and cholestatic conditions. METHODS: Functional
implications and mechanisms were investigated in rats, hepatocytic HepG2 and
HepaRG cells, human immortalized hepatocytes, and isolated perfused livers. Z-BOX
A and B were determined by liquid chromatography-tandem mass spectrometry (LC
MS/MS) in acute and acute-on-chronic liver failure and hereditary unconjugated
hyperbilirubinemia. RESULTS: Z-BOX A and B are found in similar amounts in humans
and rodents under physiological conditions. Serum concentrations increased ~20
fold during cholestatic liver failure in humans (p<0.001) and in hereditary
deficiency of bilirubin glucuronidation in rats (p<0.001). Pharmacokinetic
studies revealed shorter serum half-life of Z-BOX A compared to its regio-isomer
Z-BOX B (p=0.035). While both compounds were taken up by hepatocytes, Z-BOX A was
enriched ~100-fold and excreted in bile. Despite their reported vasoconstrictive
properties in the brain vasculature, BOXes did not affect portal hemodynamics.
Both Z-BOX A and B showed dose-dependent cytotoxicity, affected the glutathione
redox state, and differentially modulated activity of Rev-erbalpha and Rev
erbbeta. Moreover, BOXes-triggered remodeling of the hepatocellular cytoskeleton.
CONCLUSIONS: Our data provide evidence that higher-order heme degradation
products, namely Z-BOX A and B, impair hepatocellular integrity and might mediate
intra- and extrahepatic cytotoxic effects previously attributed to
hyperbilirubinemia. LAY SUMMARY: Degradation of the blood pigment heme yields the
bile pigment bilirubin and the oxidation products Z-BOX A and Z-BOX B. Serum
concentrations of these bioactive molecules increase in jaundice and can impair
liver function and integrity. Amounts of Z-BOX A and Z-BOX B that are observed
during liver failure in humans have profound effects on hepatic function when
added to cultured liver cells or infused into healthy rats.
PMID- 28412298
TI - Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound
Healing.
AB - Tight junction (TJ) proteins are known to be involved in proliferation and
differentiation. These processes are essential for normal skin wound healing.
Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin
wound healing models and tissue samples of acute and chronic human wounds and
observed major differences in localization/expression of these proteins, with
chronic wounds often showing a loss of the proteins at the wound margins and/or
in the regenerating epidermis. Knockdown experiments in primary human
keratinocytes showed that decreased claudin-1 expression resulted in
significantly impaired scratch wound healing, with delayed migration and reduced
proliferation. Activation of AKT pathway was significantly attenuated after
claudin-1 knockdown, and protein levels of extracellular signal-related kinase
1/2 were reduced. For occludin, down-regulation had no impact on wound healing in
normal scratch assays, but after subjecting the cells to mechanical stress, which
is normally present in wounds, wound healing was impaired. For both proteins we
show that most of these actions are independent from the formation of barrier
forming TJ structures, thus demonstrating nonbarrier-related functions of TJ
proteins in the skin. However, for claudin-1 effects on scratch wound healing
were more pronounced when TJs could form. Together, our findings provide evidence
for a role of claudin-1 and occludin in epidermal regeneration with potential
clinical importance.
PMID- 28412299
TI - Toll-Like Receptor 4-Independent Carbon Tetrachloride-Induced Fibrosis and
Lipopolysaccharide-Induced Acute Liver Injury in Mice: Role of Hepatic Stellate
Cells.
AB - Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is implicated in acute
and chronic liver injury; its effects are mediated predominantly via the membrane
receptor Toll-like receptor 4 (TLR4). However, TLR4-independent effects of LPS
may play important role in hepatic pathophysiology. We investigated carbon
tetrachloride (CCl4)-induced fibrosis and LPS-induced acute liver injury in wild
type (WT) and B6.B10ScN-Tlr4lps-del/JthJ [TLR4-knockout (KO)] mice. Effects of
LPS on fibrogenic hepatic stellate cells (HSCs) from WT and TLR4-KO mice were
assessed in vitro. CCl4 produced similar fibrosis and necroinflammation and
increased the mRNA and protein expression of cytokines and chemokines in WT and
TLR4-KO mice. However, circulating LPS concentration did not increase in CCl4
treated mice. Interestingly, LPS down-modulated alpha-smooth muscle actin
(activated HSC marker) and collagen 1 in both WT and TLR4-KO HSCs. LPS induced
similar activation of NF-kappaB, and stimulated the expression of cytokines and
chemokines in WT and TLR4-KO HSCs. Finally, LPS caused similar inflammation and
injury in previously untreated WT and TLR4-KO mice. The results provide evidence
of the TLR4/LPS-independent mechanisms of liver fibrosis and also indicate that
TLR4 is not entirely critical to LPS-induced acute liver injury. The results
further indicate that LPS signaling in activated HSCs might be a mechanism of
limiting liver fibrosis.
PMID- 28412301
TI - Environmental risks outweigh dopaminergic genetic risks for alcohol use and abuse
from adolescence through early adulthood.
AB - BACKGROUND: Alcohol use is a primary public health concern, particularly among
adolescents and young adults. Based on the rapidly growing field of gene
environment models, this study assessed the combined role of environmental and
dopamine-related genetic correlates of early alcohol use and abuse. METHODS:
Multilevel growth models assessed trajectories of alcohol use and intoxication
and ordered logistic regressions assessed alcohol use disorder among a sample of
12,437 youth from the nationally representative Add Health study who were
followed from mid-adolescence through early adulthood. RESULTS: Endogenous and
exogenous stressful life events and social norms supportive of alcohol use from
parents and peers were significant predictors of alcohol use, intoxication, and
alcohol use disorder, with consistent patterns across males and females. In
contrast, a dopamine-system genetic risk score (GRS) was not associated with
alcohol use trajectories nor alcohol use disorder in early adulthood, although
weak connections emerged between the GRS and growth trajectories of intoxication,
indicating that higher GRS predicted more frequent episodes of intoxication
during the transition to adulthood but not during adolescence or later 20s. No
evidence of gene-environment interactions emerged. CONCLUSIONS: Results extend a
substantial body of prior research primarily assessing single genetic
polymorphisms in the dopamine system, suggesting that dopaminergic GRSs may be
associated with more problematic alcohol behaviors at some developmental periods,
but further, that social norms and stressful life experiences are more consistent
correlates of early and problematic alcohol use among youth. These environmental
factors present potential targets for research manipulating contexts to identify
causal pathways.
PMID- 28412300
TI - Mechanisms of Retinal Damage after Ocular Alkali Burns.
AB - Alkali burns to the eye constitute a leading cause of worldwide blindness. In
recent case series, corneal transplantation revealed unexpected damage to the
retina and optic nerve in chemically burned eyes. We investigated the physical,
biochemical, and immunological components of retinal injury after alkali burn and
explored a novel neuroprotective regimen suitable for prompt administration in
emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction
measurements were performed in the anterior and posterior segment of mouse and
rabbit eyes using implantable microsensors. Tissue inflammation was assessed by
immunohistochemistry and flow cytometry. The experiments confirmed that the
retinal damage is not mediated by direct effect of the alkali, which is
effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation
reduction changes were restricted to the cornea and the anterior chamber, where
they caused profound uveal inflammation and release of proinflammatory cytokines.
The latter rapidly diffuse to the posterior segment, triggering retinal damage.
Tumor necrosis factor-alpha was identified as a key proinflammatory mediator of
retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor
necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion
cell loss. Intraocular pressure elevation was not observed in experimental alkali
burns. These findings illuminate the mechanism by which alkali burns cause
retinal damage and may have importance in designing therapies for retinal
protection.
PMID- 28412302
TI - Who benefits from computer-based brief alcohol intervention? Day-to-day drinking
patterns as a moderator of intervention efficacy.
AB - OBJECTIVE: to test if people with different day-to-day drinking patterns
benefitted differently from two brief alcohol interventions (BAIs). METHODS: A
total of 1243 job-seekers with at-risk alcohol use aged 18-64 years (64% men)
were randomized to (a) intervention tailored to the motivational stage (ST), (b)
non-stage tailored intervention (NST), or (c) assessment only (AO). ST and NST
contained individualized computer-generated feedback letters. Follow-ups were
conducted at months 3, 6, and 15. Using growth mixture models, day-to-day
drinking patterns were identified based on the number of drinks consumed on each
day in the week prior to baseline assessment. To test drinking pattern-specific
intervention effects, zero-inflated growth models were used. Outcomes were (1)
the 15-month change in the likelihood of any alcohol use and (2) the 15-month
change in the total number of drinks per week when alcohol was consumed. RESULTS:
Four day-to-day drinking patterns were found: daily medium use (2-4 drinks/day;
47%), daily low use (1-2 drinks/day; 29%), weekend only use (18%), and no use
(6%). Only persons with daily low use benefitted from intervention, with higher
odds of being abstinent after 15 months in the ST group compared to AO (odds
ratio, OR=1.67, p=0.001) and NST group (OR=1.43, p=0.035). ST worked better among
persons with daily low use compared to daily medium use (OR=1.91, p=0.001).
CONCLUSIONS: Among at-risk drinking persons with regular low-quantity alcohol
use, stage tailored BAIs may be superior over no BAI and non-stage tailored BAIs.
PMID- 28412303
TI - Laboratory analysis of risky driving at 0.05% and 0.08% blood alcohol
concentration.
AB - BACKGROUND: The public health costs associated with alcohol-related traffic
crashes are a continuing problem for society. One harm reduction strategy has
been to employ per se limits for blood alcohol concentrations (BACs) at which
drivers can legally operate motor vehicles. This limit is currently 0.08% in all
50 US states. Recently, the National Transportation Safety Board proposed
lowering the legal limit to 0.05% (NTSB, 2013). While research has well-validated
the ability of alcohol to impair driving performance and heighten crash-risk at
these BACs, relatively little is known about the degree to which alcohol might
increase drivers' risk-taking. METHODS: Risk-taking was examined in 20 healthy
adults who were each tested in a driving simulator following placebo and two
doses of alcohol calculated to yield peak BACs of 0.08% and 0.05%, the respective
current and proposed BAC limits. The drive test emphasized risk-taking by placing
participants in a multiple-lane, high-traffic environment. The primary measure
was how close drivers maneuvered relative to other vehicles on the road (i.e.,
time-to-collision, TTC). RESULTS: Alcohol increased risk-taking by decreasing
drivers' TTC at the 0.08% target BAC relative to placebo. Moreover, risk-taking
at the 0.05% target was less than risk-taking at 0.08% target BAC. CONCLUSIONS:
These findings provide evidence that reducing the legal BAC limit in the USA to
0.05% would decrease risk-taking among drivers. A clearer understanding of the
dose-response relationship between various aspects of driving behaviors, such as
drivers' accepted level of risk while driving, is an important step to improving
traffic safety.
PMID- 28412304
TI - Synergistic effect between D-AP5 and muscimol in the nucleus accumbens shell on
memory consolidation deficit in adult male Wistar rats: An isobologram analysis.
AB - The nucleus accumbens (NAc) glutamatergic and GABAergic systems are involved in
memory processes. This study was investigated the involvement of NAc shell
GABAergic system on D-AP5 induced memory consolidation deficit. The elevated plus
maze (EPM) test-retest paradigm was employed to assess memory in adult male
Wistar rats. The results indicated that post-training intra-NAc shell injection
of bicuculline (GABAA receptor antagonist) did not alter emotional memory
consolidation. However, post-training intra-NAc shell microinjection of muscimol
(GABAA receptor agonist, 0.1MUg/rat) and D-AP5 (a competitive NMDA receptor
antagonist, 4MUg/rat) decreased emotional memory consolidation, suggesting the
drugs induced amnesia. Moreover, a sub-threshold dose of muscimol (0.05MUg/rat)
potentiated the D-AP5 (2MUg/rat) response on memory consolidation impairment. On
the other hand, the middle dose of bicuculline (0.25MUg/rat) reversed memory
impairment induced by D-AP5 at the higher dose. Interestingly, there is a
synergistic effect between D-AP5 and muscimol on impairment of emotional memory
consolidation. None of the above doses changed the locomotor activity. Our
results suggest that the glutamatergic and GABAergic neurons of the NAc shell
interact with each other for modulation of emotional memory consolidation.
PMID- 28412306
TI - Time-dependent sensitization of antipsychotic effect in adolescent male and
female rats.
AB - Many behavioral and biological effects of a psychoactive drug often undergo time
dependent change following even one single drug exposure. The present study
examined whether one or two exposures of haloperidol, olanzapine or clozapine
would also induce a time-dependent change in their behavioral effects in
adolescent rats, and whether such a change vary between sexes. Adolescent Sprague
Dawley rats (<40days old) were first treated with one single injection of
haloperidol (0.05 and 0.1mg/kg, sc), clozapine (10.0 and 20.0mg/kg, sc), 2
injections of olanzapine (1.0 and 2.0mg/kg, sc) or vehicle, and tested in a
conditioned avoidance response (CAR) model or a PCP (3.20mg/kg, sc)-induced
hyperlocomotion model to assess the drug's antipsychotic-like behavioral effects.
One or three weeks later, rats were challenged with the drug and their avoidance
responses and the PCP-induced hyperlocomotion were re-assessed. One-trial
haloperidol and 2-trial olanzapine induced a sensitization, while 1-trial
clozapine induced a tolerance effect. The 1-trial haloperidol sensitization was
significantly higher at the 3-week time point than at 1-week point, especially in
the females. Clozapine tolerance in the conditioned avoidance response model also
exhibited the time-dependent increase in both sex groups. Olanzapine
sensitization in the PCP model showed a time-dependent change in a sex-dependent
fashion. Overall, the time-dependent antipsychotic sensitization and tolerance
can be demonstrated in adolescent animals. Many pharmacological (e.g. specific
drugs, drug doses), individual (e.g. male versus female) and environmental (e.g.
specific behavioral models) factors play a role in the modulation of the strength
of antipsychotic sensitization and tolerance.
PMID- 28412305
TI - Memantine improves outcomes after repetitive traumatic brain injury.
AB - Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is
common and results in significant cognitive impairment. Targeted therapies for
rmTBI are lacking, though evidence from other injury models indicates that
targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic
toxicity might mitigate rmTBI-induced neurologic deficits. However, there is a
paucity of preclinical or clinical data regarding NMDAR antagonist efficacy in
the rmTBI setting. To test whether NMDAR antagonist therapy improves outcomes
after rmTBI, mice were subjected to rmTBI injury (4 injuries in 4days) and
randomized to treatment with the NMDA antagonist memantine or with vehicle.
Functional outcomes were assessed by motor, anxiety/impulsivity and mnemonic
behavioral tests. At the synaptic level, NMDAR-dependent long-term potentiation
(LTP) was assessed in isolated neocortical slices. At the molecular level, the
magnitude of gliosis and tau hyper-phosphorylation was tested by Western blot and
immunostaining, and NMDAR subunit expression was evaluated by Western blot and
polymerase chain reaction (PCR). Compared to vehicle-treated mice, memantine
treated mice had reduced tau phosphorylation at acute time points after injury,
and less glial activation and LTP deficit 1 month after injury. Treatment with
memantine also corresponded to normal NMDAR expression after rmTBI. No
corresponding protection in behavior outcomes was observed. Here we found NMDAR
antagonist therapy may improve histopathological and functional outcomes after
rmTBI, though without consistent corresponding improvement in behavioral
outcomes. These data raise prospects for therapeutic post-concussive NMDAR
antagonism, particularly in athletes and warriors, who suffer functional
impairment and neurodegenerative sequelae after multiple concussions.
PMID- 28412307
TI - The 9th Conference on Metal Toxicity and Carcinogenesis: The conference overview.
AB - Heavy metals, such as arsenic, chromium, cadmium, nickel, mercury, and uranium
are known to cause many human diseases and health complications after
occupational or environmental exposure. Consequently, metals are environmental
health concerns. This manuscript is an overview of the 9th Conference on Metal
Toxicity and Carcinogenesis held in October 2016 in Lexington, Kentucky. Since
2000, this biennial meeting brings together experts in the field to discuss
current and prospective research in an effort to advance research pertaining to
metal toxicity and carcinogenesis. In this review we summarize the major topics
discussed and provide insight regarding current research in the field and an
account of the direction in which the field is progressing.
PMID- 28412308
TI - Genistein prevention of hyperglycemia and improvement of glucose tolerance in
adult non-obese diabetic mice are associated with alterations of gut microbiome
and immune homeostasis.
AB - Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone
genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary
GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse
model was employed to investigate the effects of GEN exposure on blood glucose
level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male
and female NOD mice were fed with either soy-based or casein-based diet, and
received GEN at 20mg/kg body weight by gavage daily. The BGL and immune responses
(represented by serum antibodies, cytokines and chemokines, and histopathology)
were monitored, while the fecal gut microbiome was sequenced for 16S ribosomal
RNA to reveal any alterations in gut microbial communities. A significantly
reduced BGL was found in NOD males fed with soy-based diet on day 98 after
initial dosing, and an improved glucose tolerance was observed on both diets. In
addition, an anti-inflammatory response (suggested by reduced IgG2b and
cytokine/chemokine levels, and alterations in the microbial taxonomy) was
accompanied by an altered beta-diversity in gut microbial species. Among the NOD
females exposed to GEN, a later onset of T1D was observed. However, the profiles
of gut microbiome, antibodies and cytokines/chemokines were all indicative of pro
inflammation. This study demonstrated an association among GEN exposure, gut
microbiome alteration, and immune homeostasis in NOD males. Although the
mechanisms underlying the protective effects of GEN in NOD mice need to be
explored further, the current study suggested a GEN-induced sex-specific effect
in inflammatory status and gut microbiome.
PMID- 28412309
TI - The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs)
with important implication in immunity.
AB - We recently demonstrated the existence of a complex hormonal balance between
steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1)
expression and immune activation, suggesting that this scaffold protein may also
be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we
investigated the effect of the doping agent nandrolone, an androgen receptor (AR)
agonist, and of p,p'DDT (dichlorodiphenyltrichloroethane) and its main metabolite
p,p'DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist,
respectively, on RACK1 expression and innate immune response. In analogy to
endogenous androgens, nandrolone induced a dose-related increase in RACK1
transcriptional activity and protein expression, resulting in increased LPS
induced IL-8 and TNF-alpha production and proliferation in THP-1 cells.
Conversely, p,p'DDT and p,p'DDE significantly decrease RACK1 expression, LPS
induced cytokine production and CD86 expression; with p,p'DDE exerting a stronger
repressor effect than p,p'DDT, consistent with its stronger AR antagonistic
effect. These results indicate that RACK1 could be a relevant target of EDCs,
responding in opposite ways to agonist or antagonist of AR, representing a bridge
between the endocrine system and the innate immune system.
PMID- 28412310
TI - Increased seizure susceptibility and other toxicity symptoms following acute
sulforaphane treatment in mice.
AB - Activation of Nrf2 with sulforaphane has recently gained attention as a new
therapeutic approach in the treatment of many diseases, including epilepsy. As a
plant-derived compound, sulforaphane is considered to be safe and well-tolerated.
It is widely consumed, also by patients suffering from seizure and taking
antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many
natural remedies and dietary supplements may increase seizure risk and
potentially interact with antiepileptic drugs, the aim of our study was to
investigate the acute effects of sulforaphane on seizure thresholds and activity
of some first- and second-generation antiepileptic drugs in mice. In addition,
some preliminary toxicity profile of sulforaphane in mice after intraperitoneal
injection was evaluated. The LD50 value of sulforaphane in mice was estimated at
212.67mg/kg, while the TD50 value - at 191.58mg/kg. In seizure tests,
sulforaphane at the highest dose tested (200mg/kg) significantly decreased the
thresholds for the onset of the first myoclonic twitch and generalized clonic
seizure in the iv PTZ test as well as the threshold for the 6Hz-induced
psychomotor seizure. At doses of 10-200mg/kg, sulforaphane did not affect the
threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal
electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg)
potentiated the anticonvulsant efficacy of carbamazepine in the maximal
electroshock seizure test. This interaction could have been pharmacokinetic in
nature, as sulforaphane increased concentrations of carbamazepine in both serum
and brain tissue. The toxicity study showed that high doses of sulforaphane
produced marked sedation (at 150-300mg/kg), hypothermia (at 150-300mg/kg),
impairment of motor coordination (at 200-300mg/kg), decrease in skeletal muscle
strength (at 250-300mg/kg), and deaths (at 200-300mg/kg). Moreover, blood
analysis showed leucopenia in mice injected with sulforaphane at 200mg/kg. In
conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety
profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients
should be further evaluated.
PMID- 28412311
TI - Cross-national investigation of the drivers of obesity: Re-assessment of past
findings and avenues for the future.
AB - In this paper we question whether prior cross-national differences in food
attitudes still exist and if so, to what extent. Due to societal evolutions such
as sedentarism and globalization, international variations in food attitudes may
not be as pronounced as currently believed. A cross-sectional web-based survey
was carried out in the United States, the United Kingdom, France and Belgium. A
total of 2167 respondents (52% women; mean age = 39.0 years, SD = 11.4)
participated. To successfully combat obesity, a joint approach focusing on food
choice and physical activity is required; therefore we included behavioral
measures by means of choice tasks for these two important drivers. Further, the
extent to which respondents subscribe to the unhealthy = tasty intuition,
together with health and taste interest were investigated. Socio-demographic
information and self-reported heights and weights were also incorporated.
Logistic regressions were fitted with weight status as the dependent variable and
the attitudinal and behavioral measures as independent variables. Our findings
indicate that having a higher interest in healthy eating decreases the chance of
being overweight (odds = 0.88) and believing that unhealthy food is tasty
significantly increases the chance of being obese by 1.18 times. Overall, we find
that food attitudes have largely converged across the countries we investigated.
PMID- 28412312
TI - Updates to a 13C metabolic flux analysis model for evaluating energy metabolism
in cultured cerebellar granule neurons from neonatal rats.
AB - A hexose phosphate recycling model previously developed to infer fluxes through
the major glucose consuming pathways in cultured cerebellar granule neurons
(CGNs) from neonatal rats metabolizing [1,2-13C2]glucose was revised by
considering reverse flux through the non-oxidative pentose phosphate pathway
(PPP) and symmetrical succinate oxidation within the tricarboxylic acid (TCA)
cycle. The model adjusts three flux ratios to effect 13C distribution in the
hexose, pentose, and triose phosphate pools, and in TCA cycle malate to minimize
the error between predicted and measured 13C labeling in exported lactate (i.e.,
unlabeled, single-, double-, and triple-labeled; M, M1, M2, and M3,
respectively). Inclusion of reverse non-oxidative PPP flux substantially
increased the number of calculations but ultimately had relatively minor effects
on the labeling of glycolytic metabolites. From the error-minimized solution in
which the predicted M-M3 lactate differed by 0.49% from that measured by liquid
chromatography-triple quadrupole mass spectrometry, the neurons exhibited
negligible forward non-oxidative PPP flux. Thus, no glucose was used by the
pentose cycle despite explicit consideration of hexose phosphate recycling.
Mitochondria consumed only 16% of glucose while 45% was exported as lactate by
aerobic glycolysis. The remaining 39% of glucose was shunted to pentose
phosphates presumably for de novo nucleotide synthesis, but the proportion
metabolized through the oxidative PPP vs. the reverse non-oxidative PPP could not
be determined. The lactate exported as M1 (2.5%) and M3 (1.2%) was attributed to
malic enzyme, which was responsible for 7.8% of pyruvate production (vs. 92.2% by
glycolysis). The updated model is more broadly applicable to different cell types
by considering bi-directional flux through the non-oxidative PPP. Its application
to cultured neurons utilizing glucose as the sole exogenous substrate has
demonstrated substantial oxygen-independent glucose utilization by aerobic
glycolysis as well as the oxidative PPP and/or reverse non-oxidative PPP, but
negligible glucose consumption by the pentose cycle.
PMID- 28412313
TI - Is trial of labor harmful in breech delivery? A cohort comparison for breech and
vertex presentations.
AB - INTRODUCTION: Planned vaginal delivery in breech presentation is accompanied by
an excess neonatal risk that has, however, rarely been compared to that of
delivery in vertex presentation. Because of the severity of complications that
can occur in long-term follow-up, the risk of asphyxia is of particular concern.
MATERIAL AND METHODS: To assess immediate neonatal status after a planned vaginal
delivery of fetuses in breech compared with vertex presentation, we planned a
retrospective hospital cohort study of singleton term deliveries from 2000 to
2011. The indicators used to assess neonatal status were: 5-min Apgar score<7,
acidosis, both moderate (pH<7.15) and severe (pH<7.0), asphyxia (pH<7.0 and base
deficit>=12.0mmol/L), transfer to the neonatal intensive care unit (NICU), and in
hospital neonatal death. RESULTS: Compared with 43,595 trials of vaginal delivery
in vertex presentation at term during the 12-year study period (93.8% of all
vertex presentations), the 665 breech deliveries for which planned vaginal
delivery was planned (43.2% of all breech presentations) had a quadrupled risk of
severe acidosis (ORa 4.3 [2.2-7.5]), but no increase in the risk of asphyxia (ORa
0.7 [0.1-3.0]), NICU transfer (ORa 0.8 [0.4-1.3]) or in-hospital death (ORa 1.3
[0.1-6.0]). Moreover, compared with the 876 planned cesareans, the risk of severe
acidosis in the 665 trials of vaginal delivery in breech presentation was four
times higher (OR 4.3 [2.3-4.7]), but we observed no increase in neither asphyxia
nor other risks studied. CONCLUSION: In our hospital, planned vaginal delivery is
safe for breech presentations because it is associated with an increase of severe
acidosis but not asphyxia.
PMID- 28412314
TI - Improving students' ability to perform a standardized foetal biometry plane using
ultrasound simulators.
AB - OBJECTIVE: The objective of this study is to assess progress made in the
ultrasound (US) measurement of femur length (FL) by students after one hour of
training on US obstetric simulators. MATERIALS AND METHODS: Medical residents and
midwives registered for the 2016 French national foetal US diploma were invited
to a 1-hour US training course with simulators. The time to acquire the FL plane
with changing foetal presentation was prospectively measured before and after the
training. Every image was recorded, and quality criteria were assessed. RESULTS:
Thirty new learners trained in foetal US were evaluated. The time needed to
measure the FL was significantly shorter in the post-test versus the pre-test
(86s versus 125, P=0.015). The quality criteria were statistically similar before
and after training regarding the angle to horizontal (10.0 degrees versus 9.6
degrees , P=0.84) and FL (31.3mm versus 32.0mm, P=0.15). CONCLUSION: The time
needed to obtain the FL plane was reduced by 30% after a 1-hour US simulation
training session.
PMID- 28412315
TI - Reporting Compliance of Stroke Trials: Cross-Sectional Analysis.
AB - BACKGROUND: The FDA mandates timely reporting of all clinical trials conducted in
the United States. However, often the results are not reported in a timely
manner, resulting in wastage of finite resources. We assessed the reporting of
results of completed stroke trials and compared the reporting trends between U.S.
and non-U.S. stroke trials. METHODS: We assessed consecutive clinical stroke
trials registered as completed in ClinicalTrials.gov between January 1, 2008 and
January 1, 2015. Descriptive data collected included study phase, study type,
participant age, number of enrolled patients, study locations, start and primary
completion dates, result availability, time to reporting (months), sponsorship,
funding sources, and publication status. We also performed manual search for
stroke trials in Pubmed, Web of Science, and Google scholar. RESULTS: Out of a
total 140 completed trials, 39 trials (35,359 patients) involved at least 1 U.S.
center and 101 trials (58,542 patients) were conducted in non-U.S. centers. Of
the trials involving at least a single U.S. center, 31 of 39 (79%) reported their
results, whereas only 6 of 31 (19%) reported their results within 1 year. Of the
trials conducted at non-U.S. centers, 72 of 101 (71%) reported their results,
whereas results for 24 of 72 (33%) trials were available within a year of
completion. The time to reporting of results was significantly lower for all the
included clinical trials in the 2012-2014 period (P < .001, Cohen's d = .726) as
compared to the 2008-2011 period. CONCLUSION: Only one-fifth of completed stroke
trials involving at least a single U.S. center report their results within 1
year. Additionally, every fifth completed trial involving stroke patients at U.S.
centers remain unreported.
PMID- 28412316
TI - Differentiating Stroke and Seizure in Acute Setting-Perfusion Computed
Tomography?
AB - BACKGROUND: Perfusion computed tomography (PCT) is part of acute stroke protocol
in many hospitals; however, its clinical utility is still being disputed. Beyond
its use in core and penumbra estimation, there is also a question about PCT role
in stroke mimics diagnosis. Case series or small, retrospective studies showed
equivocal results. This is the first published prospective, comparative study on
PCT in differentiating stroke and seizure in acute setting. METHODS: Patients
with acute focal neurologic deficits and without acute ischemic lesions on
routine CT underwent PCT and electroencephalography (EEG) within 12 hours after
symptom onset. Perfusion parameters were set up as asymmetry indices for
corresponding regions of brain hemispheres. EEG findings were assigned to 1 of 5
classes. Neurologic examination was performed using the National Institutes of
Health Stroke Scale (NIHSS). Follow-up noncontrast computed tomography was
performed on the third day after symptom onset. If no CT changes appeared,
magnetic resonance diffusion-weighted imaging was conducted. RESULTS: Final
diagnosis was hemispheric ischemic stroke in 17 patients and focal neurologic
deficits in the course of seizures (post- and intraictally) in 12 patients. Those
groups were significantly different only in one single PCT parameter-time to peak
(TTP)-in the lateral part of the middle cerebral artery territory. Analyzed
groups were not significantly different in the NIHSS scores and the EEG
evaluation. CONCLUSIONS: TTP may stay relatively when seizure is a cause of focal
neurologic deficits, but not stroke. Further, large, prospective studies are
necessary to verify the results.
PMID- 28412317
TI - Medical Treatment for Spontaneous Anticoagulation-Related Intracerebral
Hemorrhage in the Netherlands.
AB - BACKGROUND: Spontaneous anticoagulation-related intracerebral hemorrhage accounts
for up to a quarter of spontaneous intracerebral hemorrhage cases and is
associated with higher hematoma volume and a worse outcome. Guidelines recommend
rapid anticoagulant reversal but mode and timing are not specified and optimal
strategy is uncertain. Variability in everyday practice is unknown. METHODS: An
invitation to a web-based survey was sent to 85 Dutch stroke neurologists in
different hospitals, with questions about importance, timing, and medical
management of spontaneous anticoagulation-related intracerebral hemorrhage.
RESULTS: In total, 61 (72%) neurologists completed the survey. Nearly all (97%)
deemed rapid anticoagulant reversal important. A local guideline for management
of anticoagulant reversal was used in 80% of the hospitals. Most neurologists
(56%) estimated anticoagulant reversal in anticoagulation-related intracerebral
hemorrhage to start later than intravenous thrombolysis in ischemic stroke. Few
(5%) thought it was quicker. A minority (28%) of the hospitals started
anticoagulation reversal without waiting for laboratory test results or
consulting a specialist in hemostasis. Prothrombin complex concentrate was used
by all neurologists for vitamin K antagonist reversal and by most (74%) for
reversal of thrombin inhibitors and factor Xa inhibitors (72%). Anticoagulation
reversal was initiated at the emergency department according to 89% of the
respondents. CONCLUSION: Variability in logistics in acute management of
spontaneous anticoagulation-related intracerebral hemorrhage was demonstrated.
Anticoagulant reversal is deemed important, but is estimated to have a longer
door-to-needle time than alteplase in thrombolysis for ischemic stroke by most
neurologists. Several delaying factors were found. These factors might have an
impact on outcome.
PMID- 28412318
TI - Nontraditional Lipid Variables Predict Recurrent Brain Ischemia in Embolic Stroke
of Undetermined Source.
AB - OBJECTIVE: The aims of this study are, first, to calculate the risk of brain
ischemia recurrence and embolic source diagnosis in the follow-up of patients
with ESUS (embolic stroke of undetermined source) and, second, to identify the
predictors of these events including cardiologic, laboratory, and clinical
factors. METHODS: A retrospective observational cohort study of stroke patients
admitted to the stroke unit in a single tertiary hospital from 2012 to 2014 was
performed. Patients fulfilling ESUS criteria were identified and followed by
medical history review until March 2016. Statistical analysis comprised Kaplan
Meier analysis and Cox proportional hazards multivariate analysis including
clinical characteristics, cardiologic data, and blood test results. RESULTS: One
hundred and thirteen patients, 8.3% of the overall stroke patients, filled ESUS
criteria and they were younger, had less vascular risk factors, and suffered
milder strokes than the remainder of stroke patients. Median follow-up of ESUS
was 25.6 months. Risk of brain ischemia recurrence was 8.4, 10.8, and 15% at 12,
24, and 36 months, respectively, and was associated to age (HR 1.07, P = .027)
and to a higher total cholesterol (TC)/high-density lipoprotein (HDL)-cholesterol
(HR = 1.38, P = .002) and low-density lipoprotein (LDL)-cholesterol/HDL
cholesterol ratios (HR = 1.48, P = .001). The risk of major embolic source
diagnosis was 6.7, 7.8, 13.6% at 12, 24, and 36 months, and was associated to
female sex (HR = 6.05, P = .021). CONCLUSIONS: Brain ischemia recurrence
increases with age and increased values of nontraditional lipid variables, TCHDLr
and LDLHDLr, in ESUS patients, and women are more frequently diagnosed with a
major embolic source in the follow-up.
PMID- 28412319
TI - Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control
and Vascular Events in Atrial Fibrillation.
AB - BACKGROUND: Warfarin has a narrow therapeutic window. We hypothesized that
genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1)
would show stronger associations than modifiable factors with the quality of
anticoagulation control and risks for thromboembolism and hemorrhage. METHODS: In
this retrospective cohort analysis, clinical and genetic data were collected from
380 patients with atrial fibrillation (AF) who were followed for an average
observation period of 4 years. We evaluated the factors associated with time in
therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular
events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and
VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin
dose assessment interval). RESULTS: The genotypic frequency of CYP2C9*3
(rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed
dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1
1173C>T than of the VKORC1 TT genotype (61.7 +/- 16.0% versus 56.7 +/- 17.4%, P =
.031). Multivariate testing showed that the VKORC1 genotype and anticoagulation
service were independently related to labile INRs (TTR <65%). Vascular events
were observed in 66 patients (18.4%) during the study period. A Cox proportional
hazard model showed that the use of anticoagulation service and patients'
characteristics, such as AF-thromboembolic risk (CHA2DS2-VASc score: Congestive
heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous
Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years,
female) and consequence (neurologic disability), but not genetic factors, were
independently associated with vascular events. CONCLUSIONS: Both genetic factor
(VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the
quality of anticoagulation control. However, clinical events were more strongly
associated with patient characteristics and clinical efforts than with genetic
factors.
PMID- 28412320
TI - Glibenclamide ameliorates cerebral edema and improves outcomes in a rat model of
status epilepticus.
AB - Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a
promising neuron protectant in various neurological disorders. This study aimed
to determine whether GBC improves survival and neurological outcome of status
epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h
(n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group
received a loading dose of 10 MUg/kg of GBC, followed by 1.2 MUg/6 h for 3 days,
while same dose of vehicle was used as control. The 28-day survival rate in the
GBC group (11/23) was significantly higher than that in the vehicle group (8/36).
In addition, the frequency and duration of spontaneous recurrent seizures in SE
rats were profoundly reduced by GBC but not by vehicle treatment. Moreover,
cognitive impairment was observed in the SE rats at day 28, which was reversed by
GBC treatment. Meanwhile, cerebral edema, as well as neuronal loss, was decreased
in several brain areas in the GBC group. Additionally, on the molecular basis,
the subunits of sulfonylurea receptor 1/transient receptor potential M4 (SUR1
TRPM4) heterodimer were both strongly upregulated after SE but partly suppressed
by GBC treatment. Furthermore, gene knockdown of Trpm4 in SE rats reduced BBB
disruption and neuronal loss, similar to the inhibitory effects with GBC
treatment. Taken together, GBC treatment markedly improved survival and
neurologic outcomes after SE. The salutary effects of GBC were correlated to the
alleviation of cerebral edema and reduction in neurological injury via down
regulation of SUR1-TRPM4 channel.
PMID- 28412321
TI - EGCG ameliorates diet-induced metabolic syndrome associating with the circadian
clock.
AB - In response to the daily light-dark (LD) cycle, organisms on Earth have evolved
with the approximately 24-h endogenous oscillations to coordinate behavioral and
physiological processes, including feeding, sleep, and metabolism homeostasis.
Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose
is intimately connected with a series of metabolic disorders. Previous studies
revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic
misalignment; however, only a few reports have focused on its potential effect on
directly manipulating circadian rhythms to ameliorate metabolic syndrome. Our
goal was to investigate the regulating effect of EGCG treatment on metabolic
misalignment triggered by a high-fat and high-fructose diet (HFFD) associating
with the circadian clock. Our results indicated that HFFD treatment partially
exhibited poor circadian oscillations of the core clock gene and the clock
controlled gene in the liver and fat relative to the control group. EGCG
administration may ameliorate the diet-dependent decline in circadian function by
controlling the Sirt1-PGC1alphaloop, implying the existence of an EGCG
entrainable oscillator. Subsequently, reducing fatty acid synthesis and elevating
beta-oxidation in the liver coupled with the increasing brown adipose tissue
(BAT) energy expenditure observed in the EGCG group of mice prevented the
adipocyte hypertrophy and fat accumulations common to BAT and white adipose
tissue (WAT) derived from the HFFD mice. This study is the first to provide
compelling evidences that EGCG may ameliorate diet-induced metabolic misalignment
by regulating the rhythmic expression of the circadian clock genes in the liver
and fat.
PMID- 28412322
TI - MicroRNA-130b transcriptionally regulated by histone H3 deacetylation renders Akt
ubiquitination and apoptosis resistance to 6-OHDA.
AB - Apoptosis of DA neurons is a contributing cause of disability and death for
Parkinson's disease (PD). Akt may become a potential therapeutic target for PD
since Akt has been deactivated during DA neuron apoptosis. We previously
demonstrated that Akt confers apoptosis resistance against 6-OHDA in DA neuron
like PC12 cells, yet the underlying mechanisms accounted for this are not fully
understood. Here we report that microRNA-130b (miR-130b)-dependent and
cylindromatosis (CYLD) repression-mediated Akt ubiquitination renders apoptosis
resistance of PC12 cells to 6-OHDA, which elicits histone H3 deacetylation
induced transcriptional downregulation of miR-130b vice versa. CYLD deficiency
ubiquitinates Akt at Lys63, thereby phosphorylating Akt and antagonizing 6-OHDA
initiated apoptosis. MiR-130b targetedly represses CYLD and increases apoptosis
resistance to 6-OHDA. CYLD repression by miR-130b restores Akt ubiquitination and
activation, GSK3beta and FoxO3a phosphorylation, FoxO3a removal from Bim promoter
as well as Bim downregulation during 6-OHDA administration. CYLD deficiency
mediated Akt activation is instrumental for the apoptosis-resistant phenotypes of
miR-130b. In addition, 6-OHDA transcriptionally downregulates miR-130b through
recruitment of HDAC3 at the promoter. Furthermore, EPO potentiates the ability of
miR-130b to activate Akt and augment apoptosis resistance. Our findings identify
the apoptosis-resistant function of miR-130b and suggest that histone H3
deacetylation plays a pivotal role in regulating miR-130b transcription in
response to 6-OHDA.
PMID- 28412324
TI - Nanoformulation-based sequential combination cancer therapy.
AB - Although combining two or more treatments is regarded as an indispensable
approach for effectively treating cancer, the traditional cocktail-based
combination therapies are seriously limited by coordination issues that fail to
account for differences in the pharmacokinetics and action sites of each drug.
The careful manipulation of dosing regimens, such as by the sequential
application of combination treatments, may satisfy the temporal and spatial needs
of each drug and achieve successful combination antitumor therapy. Nanotechnology
based carriers might be the best tools for sequential combination therapy, as
they can be loaded with multiple cargos and may provide targeted and sustained
delivery to target tumor cells. Single nanoformulations capable of sequentially
releasing drugs have shown synergistic anticancer activity, such as by
sensitizing tumor cells through cascaded drug delivery or remodeling the tumor
vasculature and microenvironment to enhance the tumor distribution of
nanotherapeutics. This review highlights the use of nanotechnology-based
multistage drug delivery for cancer treatment, focusing on the ability of such
formulations to enhance antitumor efficacy by applying sequential treatment and
modulating dosing regimens, which are challenges currently being faced in the
clinic.
PMID- 28412323
TI - Single CpG site methylation controls estrogen receptor gene transcription and
correlates with hormone therapy resistance.
AB - Hormone therapy is the most effective treatment for patients with estrogen
receptor alpha-positive breast cancers. However, although resistance occurs
during treatment in some cases and often reflects changed estrogen receptor alpha
status, the relationship between changes in estrogen receptor alpha expression
and resistance to therapy are poorly understood. In this study, we identified a
mechanism for altered estrogen receptor alpha expression during disease
progression and acquired hormone therapy resistance in aromatase inhibitor
resistant breast cancer cell lines. Subsequently, we investigated promoter
switching and DNA methylation status of the estrogen receptor alpha promoter, and
found marked changes of methylation at a single CpG site (CpG4) in resistant
cells. In addition, luciferase reporter assays showed reduced transcriptional
activity from this methylated CpG site. This CpG region was also completely
conserved among species, suggesting that it acts as a methylation-sensitive Ets-2
transcription factor binding site, as confirmed using chromatin
immunoprecipitation assays. In estrogen receptor alpha-positive tumors, CpG4
methylation levels were inversely correlated with estrogen receptor alpha
expression status, suggesting that single CpG site plays an important role in the
regulation of estrogen receptor alpha transcription.
PMID- 28412325
TI - Designing metal-contained enzyme mimics for prodrug activation.
AB - Enzyme-activated prodrug therapy (EAPT) is a widely-used and effective treatment
method for cancer by converting prodrugs into drugs at the demanded time and
space, whose key step is prodrug activation. Traditional prodrug activations are
mostly dependent on natural enzymes, which are unstable, expensive and hard to be
functionalized. The emerging enzyme mimics, especially the metal-contained enzyme
mimics (MEMs), provide a potential chance for improving the traditional EAPT
because of their high stability, low cost and easiness of preparation and
functionalization. The existing MEMs can be classified into three categories:
catalytic core-scaffold MEM (csMEM), nanoparticle MEM (npMEMs) and metal-organic
framework (MOF) MEM (mofMEM). These MEMs can mimic diverse functions
corresponding to natural enzymes, and some of which are potentially used in
prodrug activation, such as DNase, RNase, carbonate esterase, etc. In this
review, we briefly summarize the MEMs according to their structure and
composition, and highlight the successful and potential applications for prodrug
activation mediated by hydrolase-like and oxidoreductase-like MEMs.
PMID- 28412326
TI - No Acute Changes in LVEF Observed With Concurrent Trastuzumab and Breast
Radiation With Low Heart Doses.
AB - INTRODUCTION/BACKGROUND: Treatment for HER2-postitive breast cancer often
includes trastuzumab, breast/chest wall (CW) radiation (RT), and anthracyclines,
all of which have cardiac toxicity. We aimed to evaluate the relationship between
heart dose and acute left ventricular ejection fraction (LVEF) changes in
patients who received concurrent trastuzumab and breast/CW RT with and without
anthracycline use. PATIENTS AND METHODS: We retrospectively reviewed all
nonmetastatic breast cancer patients from 2008 to 2015 who received concurrent
trastuzumab and breast/CW RT. Baseline LVEF was compared with the LVEF closest to
treatment completion as well as with the lowest post-treatment LVEF. LVEF changes
were correlated with laterality, heart dosimetric parameters, and doxorubicin
use. RESULTS: Eighty-eight patients were included in our analysis. The median
follow-up was 45 months. Forty-one patients were right-sided and 47 left-sided.
Thirty-one patients received doxorubicin, 16 right-sided and 15 left-sided. Mean
heart dose was 1.10 Gy and 3.63 Gy for right- and left-sided patients,
respectively (P < .001). In the entire cohort, a significant LVEF decrease of
3.0% was observed pre- and post-treatment. There was a significant effect of
doxorubicin (P = .013) and a nonsignificant effect of RT laterality (P = .088) on
LVEF change. The test of interaction between doxorubicin and laterality was not
significant (P = .90). No significant association was found between LVEF change
and heart dosimetric parameters, including percent volume of heart receiving 5 Gy
(V5), 10 Gy (V10), 20 Gy (V20), and 45 Gy (V45), and maximum dose. Similar
results were found when baseline LVEF was compared with the lowest post-treatment
LVEF. CONCLUSION: With cardiac doses < 4 Gy, declines in LVEF were not related to
tumor laterality or heart dosimetric parameters. Statistically significant LVEF
decreases were mainly attributed to doxorubicin.
PMID- 28412327
TI - Place over traits? Purchasing edibles from medical marijuana dispensaries in Los
Angeles, CA.
AB - OBJECTIVES: To examine discrete purchasing behaviors of marijuana-infused edibles
from medical marijuana dispensaries with the aim to identify potential venue- and
individual-level targets for prevention. METHODS: Two-stage, venue-based sampling
approach was used to randomly select patrons exiting 16 medical marijuana
dispensaries in Los Angeles, California during Spring 2013. Hierarchical
generalized linear modeling was used to examine the likelihood of purchasing
edibles among 524 patrons reporting a discrete purchase regressed on
characteristics of the sampled dispensaries and their patrons. RESULTS: At a
venue level, patrons were more likely to purchase edibles from dispensaries
located within Census tracts with higher median incomes or in close proximity to
a higher number of dispensaries. At an individual level, patrons who identified
as Black or Hispanic were associated with a lower likelihood of purchasing
edibles when compared to patrons who identified as other non-White, non-Hispanic
race/ethnicity. CONCLUSIONS: Place-based policies focused on regulating edible
sales through dispensaries may be fruitful in influencing access to edibles.
Additionally, social marketing campaigns may benefit from targeting both
locations where edible purchases are more likely and populations who are more
likely to purchase edibles.
PMID- 28412328
TI - Budded baculovirus particles as a source of membrane proteins for radioligand
binding assay: The case of dopamine D1 receptor.
AB - INTRODUCTION: G-protein-coupled receptors have become very important drug targets
and therefore ligand binding assays for these receptors are an essential part of
drug discovery. Among a variety of experimental systems, the radioligand binding
assay has remained as one of the main methods in this field for decades. Usually
cell membranes or tissues are used in these experiments, however in this article
we demonstrate that baculoviruses produced in Sf9 cells display recombinant
receptors on their surface and therefore can be used in radioligand binding
assay. METHODS: We have used baculoviruses with dopamine D1 receptors as a model
system to validate the usage of this receptor preparation in radioligand binding
experiments. In order to collect membrane receptors and separate free
radioligand, we have applied FilterMate Harvester with Filtermat B. RESULTS:
Using baculoviruses with dopamine D1 receptors as a model system, we have shown
that this is a suitable preparation for conventional radioligand binding assay.
Here, all the experiments were performed using the dopamine D1-like receptor
specific radioligand [3H]SCH23390. There were no significant differences between
binding parameters determined in membranes of Sf9 cells and baculovirus
particles. Similar pIC50 and Ki values were also determined in competition
binding assays with HEK293 cell membranes. DISCUSSION: All the results obtained
with baculovirus preparation were in good agreement with the data obtained in
parallel experiments with membrane preparations from Sf9 and HEK293 cells
expressing dopamine D1 receptors. Shape uniformity, homogeneous distribution and
slow sedimentation of the membranes are some of the advantages of baculovirus
preparations, which prove them as promising source of membrane proteins for
routine and high throughput analysis.
PMID- 28412329
TI - Comparison of pro-amnesic efficacy of scopolamine, biperiden, and phencyclidine
by using passive avoidance task in CD-1 mice.
AB - INTRODUCTION: Memory disorders accompany numerous diseases and therapies, and
this is becoming a growing medical issue worldwide. Currently, various animal
models of memory impairments are available; however, many of them require high
financial outlay and/or are time-consuming. A simple way to achieve an efficient
behavioral model of cognitive disorders is to inject defined drug that has pro
amnesic properties. Since the involvement of cholinergic and glutamatergic
neurotransmission in cognition is well established, the utilization of a
nonselective muscarinic receptor antagonist, scopolamine (SCOP), a selective M1
muscarinic receptor antagonist, biperiden (BIP), and a non-competitive N-methyl-d
aspartate (NMDA) receptor antagonist, phencyclidine (PCP) seems to be reliable
tools to induce amnesia. As the determination of their effective doses remains
vague and the active doses vary significantly in laboratory settings and in mouse
species being tested, the aim of this study was to compare these three models of
amnesia in CD-1 mice. METHODS: Male Swiss Albino mice were used in passive
avoidance (PA) test. All the compounds were administered intraperitoneally (ip)
at doses 1mg/kg, 5mg/kg, and 10mg/kg (SCOP and BIP), and 1mg/kg, 3mg/kg, and
6mg/kg (PCP). RESULTS: In the retention trial of the PA task, SCOP and PCP led to
the reduction of step-through latency at all the tested doses as compared to
control, but BIP was effective only at the dose of 10mg/kg. CONCLUSION: This
study revealed the effectiveness of SCOP, PCP, and BIP as tools to induce
amnesia, with the PCP model being the most efficacious and SCOP being the only
model that demonstrates a clear dose-response relationship.
PMID- 28412330
TI - Re: Cambareri et al.: Do Overweight and Obese Pediatric Stone Formers Have
Differences in Metabolic Abnormalities Compared With Normal-weight Stone Formers?
(Urology 2017;101:26-30).
PMID- 28412331
TI - Are We Using the Best Tumor Size Cut-points for Renal Cell Carcinoma Staging?
AB - OBJECTIVE: To compare the predictive ability for oncologic outcomes among current
tumor size cut-points and clinically relevant alternatives to determine which are
optimal. METHODS: Patients who underwent radical or partial nephrectomy between
1970 and 2010 for T1-2Nx/N0M0 renal cell carcinoma (RCC) were identified.
Associations between tumor size and progression-free survival (PFS) and cancer
specific survival (CSS) were evaluated using Kaplan-Meier analyses and Cox
models. Predictive ability was assessed using c-indexes. RESULTS: The cohort
included 3304 patients with a median age of 63 years (interquartile range 53,
70). Median follow-up among survivors was 9.9 years (interquartile range 6.9,
14.3). There were 536 patients who progressed and 354 who died from RCC. For RCC
tumors <=3.0 cm, 10-year PFS and CSS rates were 93%-95% and 97%-99%,
respectively. For tumors >3.0-4.0 cm, PFS and CSS began to decline (91% and 95%,
respectively), with further gradual declines in PFS and CSS with increasing tumor
size. Plots of hazard ratios for progression and RCC death as a function of tumor
size did not reveal major inflection points. Differences in discrimination based
on various combinations of tumor-size cut-points for progression or RCC death
were small, with c-indexes ranging between 0.691-0.704 and 0.734-0.750,
respectively. CONCLUSION: RCC tumors <=3.0 cm in size are associated with
favorable outcomes. Thereafter, risks of progression and RCC death increase
gradually with tumor size, with no compelling biological reason to endorse a
given cut-point over another.
PMID- 28412332
TI - Congenital Aphallia: Novel Use of Acellular Dermal Matrix During Scrotal Flap
Phalloplasty.
AB - Phallic reconstruction is an important part of management for congenital
aphallia. Scrotal flap phalloplasty has been described in pediatric patients to
create the appearance of a nonfunctioning phallus. We describe a modified scrotal
flap technique with the addition of an acellular dermal matrix patch (AlloDerm)
to provide additional girth and support to the phallus. The postoperative
cosmetic outcome has been satisfactory and there is no documented complication
over a 12-month follow-up. AlloDerm dermal matrix can be a safe addition to
phallic reconstruction and its overall application needs to be further studied.
PMID- 28412333
TI - Reply by the Authors.
PMID- 28412334
TI - Ovotestis in Adolescence: 2 Case Reports.
AB - We present 2 patients found to have ovotesticular disorder of sexual development
(otDSD) in late adolescence. Two 15-year-old phenotypically male patients
presented to a large pediatric hospital with different complaints: 1 with concern
for testicular rupture after a straddle injury; 1 with gynecomastia. Further
workup, including imaging and laboratory tests, was performed before surgical
exploration. The first patient had unilateral ovotestis, contralateral testis,
and SRY-negative 46,XX karyotype. The second patient with gynecomastia had
unilateral ovotestis with hemi-uterus and fallopian tube, contralateral ovarian
tissue, and 46,XX/47,XXY Klinefelter mosaic karyotype. Although rare,
phenotypically normal male patients may present later with ovotesticular disorder
of sexual development.
PMID- 28412335
TI - Metabolic Syndrome Does Not Increase the Risk of Ejaculatory Dysfunction in
Patients With Lower Urinary Tract Symptoms and Benign Prostatic Enlargement: An
Italian Single-center Cohort Study.
AB - OBJECTIVE: To evaluate the relationship between metabolic syndrome (MetS) and
ejaculatory dysfunction (EjD) in patients with lower urinary tract symptoms and
benign prostatic enlargement. MATERIALS AND METHODS: From 2012 to 2016, a
consecutive series of men with lower urinary tract symptoms and benign prostatic
enlargement who were attending our prostate clinic were evaluated using the
International Prostate Symptom Score (IPSS) and were subsequently enrolled into a
prospective database. All patients were assessed using the short form of the
International Index of Erectile Function (IIEF-SF) and the Male Sexual Health
Questionnaire ejaculatory dysfunction short form (MSHQ-EjD-SF) that evaluates the
ability to ejaculate, the ejaculation force, the ejaculation volume, and
subjective bother associated with EjD. MetS was defined according to the Adult
Treatment Panel III criteria. RESULTS: A total of 220 patients were enrolled; 48
of 220 patients (22%) presented a MetS. Mean age was 70 +/- 8 years, mean IPSS
was 8.3 +/- 6.2, mean IIEF score was 17.3 +/- 7.9, and mean MSHQ-EjD-SF was 9.9
+/- 4.7. Overall, 109 of 220 patients (50%) were affected by a moderate or severe
EjD. On multivariate analysis, age (odds ratio [OR]: 1.058, 95% confidence
interval [CI]: 1.016-1.123; P = .007), IIEF score (OR: 0.899, 95% CI: 0.856
0.943; P = .000), and IPSS (OR: 1.065, 95% CI: 1.011-1.123; P = .018) were found
to be predictors of EjD. In our series MetS was not found to be predictive of
EjD. CONCLUSION: In our single-center study, MetS has no influence on the EjD
evaluated with the MSHQ-EjD-SF.
PMID- 28412336
TI - Antiageing activities of water-soluble chitosan from Clanis bilineata larvae.
AB - Water extracts were prepared using water-soluble chitosan from Clanis bilineata
larva skin. This study also investigated antioxidant and antiageing activities of
water-soluble chitosan. Water-soluble chitosan of Clanis bilineata larva skin
(CBLSWSC) showed considerable scavenging activities on superoxide anion and
hydroxyl radicals and reducing capacity. Different doses of CBLSWSC were
intragastrically administered on a d-galactose-induced-aged mouse model over a
period of six weeks. Intragastric CBLSWSC administration significantly increased
activities of superoxide dismutase and glutathione peroxidase and inhibited
formation of malondialdehyde in brains and sera of mice in a dose-dependent
manner. Results suggest that CBLSWSC exhibits high antioxidant activity and can
be developed as potential dietary supplement to retard ageing in humans.
PMID- 28412337
TI - An overview on molecular chaperones enhancing solubility of expressed recombinant
proteins with correct folding.
AB - The majority of research topics declared that most of the recombinant proteins
have been expressed by Escherichia coli in basic investigations. But the majority
of high expressed proteins formed as inactive recombinant proteins that are
called inclusion body. To overcome this problem, several methods have been used
including suitable promoter, environmental factors, ladder tag to secretion of
proteins into the periplasm, gene protein optimization, chemical chaperones and
molecular chaperones sets. Co-expression of the interest protein with molecular
chaperones is one of the common methods The chaperones are a group of proteins,
which are involved in making correct folding of recombinant proteins. Chaperones
are divided two groups including; cytoplasmic and periplasmic chaperones.
Moreover, periplasmic chaperones and proteases can be manipulated to increase the
yields of secreted proteins. In this article, we attempted to review cytoplasmic
chaperones such as Hsp families and periplasmic chaperones including; generic
chaperones, specialized chaperones, PPIases, and proteins involved in disulfide
bond formation.
PMID- 28412338
TI - Purification, in vitro antioxidant and in vivo anti-aging activities of
exopolysaccharides by Agrocybe cylindracea.
AB - The in vitro antioxidant and in vivo anti-aging activities in D-galactose-induced
aging mice of exopolysaccharides (EPS) and its fractions (EPS-1, EPS-2 and EPS-3)
by Agrocybe cylindraceas were investigated presently. The scavenging effects of
EPS-2 on hydroxyl (HO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were
97.1+/-4.25% and 90.23+/-3.25%, while the reducing power reached 1.18+/-0.08 at
120mg/L, which were higher than EPS, EPS-1 and EPS-3 at 1000mg/L. The EPS showed
potential anti-aging activities via reducing the contents of malonaldehyde (MDA)
and total cholesterol (TC), as well as increasing the activities of superoxide
dismutase (SOD) activities, glutathione peroxidase (GSH-Px) activities, and total
antioxidant capacity (T-AOC). Additionally, the monosaccharide analysis showed
EPS contained rhamnose and glucose with the molar ratio of 2.8:1. These results
demonstrated that EPS could be used as functional foods and natural drugs on
preventing and mitigating the aging process.
PMID- 28412339
TI - Purification and functional properties of a novel glucoamylase activated by
manganese and lead produced by Aspergillus japonicus.
AB - Microbial amylases are used to produce ethanol, glucose and can be applied in
textiles products, detergents and other industries. This study aimed to determine
the best carbon source concentration to induce the amylase production by A.
japonicus, and its purification and biochemical characterization. For that, this
fungus was cultivated in Khanna medium, pH 5.5, for 4 days, at 25 degrees C, in
static condition, supplemented with potato starch and maltose in different
concentrations. The fungal crude enzymatic extract was purified in a unique
elution in DEAE-cellulose column and the molecular mass was determined as 72kDa.
The optimum temperature and pH was 65 degrees C and 5.0, respectively. Amylase
remained 75% of its activity after one hour at 50 degrees C and was stable in the
pH range 3.0-7.0. The analysis of the end-products by thin layer chromatography
showed only glucose formation, which characterizes the purified enzyme as a
glucoamylase. Amylopectin was the best substrate for the enzyme assay and Mn+2
and Pb+2 were good glucoamylase activators. This activation, in addition to the
biochemical characteristics are important results for future biotechnological
applications of this glucoamylase in the recycling and deinking process by the
paper industries.
PMID- 28412340
TI - Levan promotes antiproliferative and pro-apoptotic effects in MCF-7 breast cancer
cells mediated by oxidative stress.
AB - Exopolysaccharides are high-valued bio-products produced by various microbial
species and have been described to possess biological response modifying
activities. These bio-products have been effective as therapeutic agents in
various human disease conditions. The objective of this study was to examine the
effects of levan (a (2->6)-beta-d-fructan) produced on sucrose by the halophilic
bacterium, Halomonas smyrnensis AAD6T, in human breast cancer MCF-7 cells. MCF-7
cells were exposed to levan for 24 and 48h. The antiproliferative activity was
analyzed by the MTT assay. Oxidative stress was measured by the CM-H2DCFDA assay,
and cell apoptosis was analyzed by the caspase-3/7 assay. Cell cycle was analyzed
by flow cytometry and gene expression was determined by RT-PCR. Levan showed a
time- and concentration-dependent antiproliferative activity, and this effect was
associated with an increase in cell apoptosis and oxidative stress. In addition,
levan increased the gene expression of p53 and p27. Here we demonstrated that
levan exhibited an antiproliferative effect that was mediated by an increase in
apoptosis and oxidative stress.
PMID- 28412341
TI - Chitosan: A potential biopolymer for wound management.
AB - It has been seen that slow healing and non-healing wounds conditions are
treatable but still challenging to humans. Wound dressing usually seeks for
biocompatible and biodegradable recipe. Natural polysaccharides like chitosan
have been examined for its antimicrobial and healing properties on the basis of
its variation in molecular weight and degree of deacetylation. Chitosan adopts
some vital characteristics for treatment of various kinds of wounds which include
its bonding nature, antifungal, bactericidal and permeability to oxygen. Chitosan
therefore has been modified into various forms for the treatment of wounds and
burns. The purpose of this review article is to understand the exploitation of
chitosan and its derivatives as wound dressings. This article will also provide a
concise insight on the properties of chitosan necessary for skin healing and
regeneration, particularly highlighting the emerging role of chitosan films as
next generation skin substitutes for the treatment of full thickness wounds.
PMID- 28412342
TI - Recent advances in the development of novel protein scaffolds based therapeutics.
AB - Antibodies occupy a central position when it comes to binding proteins with
desired antigenic specificities. During the past decade, a plethora of
recombinant or humanized versions of antibodies have entered clinical settings
with outstanding accomplishments. Yet, they suffer from several drawbacks such as
high molecular weight, limited tissue penetration, instability, high production
cost, requirement for large doses and potential cytotoxicity. As a result, new
generation of receptor proteins has been developed, that are derived from small
and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds".
Combinatorial protein engineering has tremendous scope in the development of
these protein scaffolds with immunoglobulin like specificity and/or prescribed
binding functions. The advancement made in this regard can boast of developing
various validated Ig based and non-Ig protein scaffolds with desirable
therapeutic potential. The newly emerging technology has profound scope in
translational biology and offer matching replacement for existing
immunotherapeutic agents. Only few data from early clinical studies are available
yet, but many more are likely to come in the near future. Here, we provide a
glimpse of recent clinical advances in the field of existing protein scaffolds.
PMID- 28412343
TI - Structural characterization and immunomodulatory activity of a novel
polysaccharide from Pteridium aquilinum.
AB - PAP1-A, a novel heteropolysaccharide with an average molecular mass of
1.35*105Da, was isolated from Pteridium aquilinum using a combination of
chromatography by DEAE Sepharose Fast Flow and Sepharose 4B. The monosaccharide
component of PAP1-A was L-rhamnose, L-arabinose, L-fucose, D-xylose, D-mannose, D
glucose and D-galactose in the molar ration of 1.82: 1.53: 1.42: 1.31: 5.24: 1:
12.35. The predicted structure of PAP1-A was established to be a complex
polysaccharide with a main chain consisted of alpha-(1->4)-linked galactose
partially substituted at O-6 position, with the (1->2)-linked xylose, (1->3)
linked arabinose, (1->3)-linked rhamnose, (1->3,6)-linked mannose, and (1->6)
linked mannose, as branches. Fucose, glucose, mannose, and rhamnose were located
at the termini of the branches. The immunomodulatory activity assay showed that
PAP1-A could significantly promote the RAW264.7 cells proliferation and induce
the production of NO from RAW264.7 cells. Therefore, PAP1-A shows as a potent
immunomodulator with potential applications in the medical and food industries.
PMID- 28412344
TI - Insights into structure and function of high pressure-modified starches with
different crystalline polymorphs.
AB - The effect of high pressure (HP) treatment at 200-600MPa for 30min on properties
of three starches with different polymorphs was investigated. HP treatment
altered greatly the morphology of wheat starch, especially at 400MPa or higher.
The crystallinity of wheat starch decreased from 22.6% for native starch to 3.4%
for starch after treatment at 600MPa. The short-range molecular order as measured
by FTIR and Raman spectroscopy decreased with increasing treatment pressure. HP
treatment had little effect on structural properties of potato and yam starches,
except for yam starch after treatment at 600MPa. HP treatment decreased the
pasting viscosities of wheat starch except for the treatment at 200MPa, which
increased the peak, trough and final viscosities by 6.7, 11.1 and 5.7%,
respectively. The peak viscosity of potato and yam starches was increased
respectively by 14.0 and 11.3% after HP treatment at 600MPa. HP treatment at
600MPa enhanced greatly the final digestion percentages of wheat and yam starch
by 20 and 26.4%, but had little effect on potato starch. The above results showed
that wheat starch was more susceptible to the effects of HP treatment than did
yam and potato starches, and that C-type yam starch behaved more likely the B
type potato starch to HP treatment.
PMID- 28412345
TI - A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via
suppressing miR-141 by targeting TGF-beta1.
AB - Circular RNAs (circRNAs) are a novel type of endogenous noncoding RNA gaining
research interest in recent years. Despite this increase in interest, the
mechanism of circRNAs in the pathogenesis of multiple cardiovascular diseases,
particularly myocardial fibrosis, is rarely reported. In the following study, the
expression profiles and potential mechanisms of circRNAs in mice myocardial
fibrosis models in vitro are investigated. Previous research examining circRNA
expression profiles of diabetic db/db mice myocardium using circRNA microarray
found 43 circRNAs were abnormally expressed, including 24 up-regulated circRNAs
and 19 down-regulated circRNAs. Furthermore, circRNA_010567 was markedly up
regulated in diabetic mice myocardium and cardiac fibroblasts (CFs) treated with
Ang II. Bioinformatics analysis predicted circRNA_010567, sponge miR-141 and miR
141 directly target TGF-beta1, which was validated by dual-luciferase assay.
Subsequently, functional experiments revealed circRNA_010567 silencing could up
regulate miR-141 and down-regulate TGF-beta1 expression, and suppress fibrosis
associated protein resection in CFs, including Col I, Col III and alpha-SMA.
Results demonstrate the circRNA_010567/miR-141/TGF-beta1 axis plays an important
regulatory role in the diabetic mice myocardial fibrosis model. The present study
characterizes a new function of circRNA in the pathogenesis of myocardial
fibrosis in a diabetic mouse model, providing novel insight for circRNA-miRNA
mRNA in cardiovascular disease.
PMID- 28412346
TI - Superoxide is the critical driver of DOPAL autoxidation, lysyl adduct formation,
and crosslinking of alpha-synuclein.
AB - Parkinson's disease has long been associated with redox imbalance and oxidative
stress in dopaminergic neurons. The catecholaldehyde hypothesis proposes that 3,4
dihydroxyphenylacetaldehyde (DOPAL), an obligate product of dopamine catabolism,
is a central nexus in a network of pathways leading to disease-state
neurodegeneration, owing to its toxicity and potent ability to oligomerize alpha
synuclein, the main component of protein aggregates in Lewy bodies. In this work
we examine the connection between reactive oxygen species and DOPAL autoxidation.
We show that superoxide propagates a chain reaction oxidation, and that this
reaction is dramatically inhibited by superoxide dismutase. Moreover, superoxide
dismutase prevents DOPAL from forming dicatechol pyrrole adducts with lysine and
from covalently crosslinking alpha-synuclein. Given that superoxide is a major
radical byproduct of impaired cellular respiration, our results provide a
possible mechanistic link between mitochondrial dysfunction and synuclein
aggregation in dopaminergic neurons.
PMID- 28412347
TI - Interaction of KRas4b with anionic membranes: A special role for PIP2.
AB - KRas4b is a small G-protein whose constitutively active oncogenic mutants are
present in 90% of pancreatic cancers. Using fully post-translationally modified
KRAS4b, we investigated the role of lipid identity in the recruitment of KRas4b
to a membrane surface of defined composition. Application of a newly developed
single frequency fluorescence anisotropy decay experiment to this system revealed
that KRas4b has a significant binding preference for Nanodisc bilayers containing
PIP2. We conducted molecular dynamics simulations to look for an origin of this
specificity. In the case of membranes containing PIP2 the protein formed long
lived salt bridges with PIP2 head groups but not the monovalent DMPS, explaining
the experimentally observed lipid specificity. Additionally, we report that PIP2
forms key contacts with Helix-4 on the catalytic domain of KRas4b that orient the
protein in a manner expected to facilitate association with upstream and
downstream signaling partners.
PMID- 28412348
TI - Closed-channel culture system for efficient and reproducible differentiation of
human pluripotent stem cells into islet cells.
AB - Human pluripotent stem cells (hPSCs) are thought to be a promising cell-source
solution for regenerative medicine due to their indefinite proliferative
potential and ability to differentiate to functional somatic cells. However,
issues remain with regard to achieving reproducible differentiation of cells with
the required functionality for realizing human transplantation therapies and with
regard to reducing the potential for bacterial or fungal contamination. To meet
these needs, we have developed a closed-channel culture device and corresponding
control system. Uniformly-sized spheroidal hPSCs aggregates were formed inside
wells within a closed-channel and maintained continuously throughout the culture
process. Functional islet-like endocrine cell aggregates were reproducibly
induced following a 30-day differentiation protocol. Our system shows an easily
scalable, novel method for inducing PSC differentiation with both purity and
functionality.
PMID- 28412349
TI - Light-induced protein degradation in human-derived cells.
AB - Controlling protein degradation can be a valuable tool for posttranslational
regulation of protein abundance to study complex biological systems. In the
present study, we designed a light-switchable degron consisting of a light oxygen
voltage (LOV) domain of Avena sativa phototropin 1 (AsLOV2) and a C-terminal
degron. Our results showed that the light-switchable degron could be used for
rapid and specific induction of protein degradation in HEK293 cells by light in a
proteasome-dependent manner. Further studies showed that the light-switchable
degron could also be utilized to mediate the degradation of secreted Gaussia
princeps luciferase (GLuc), demonstrating the adaptability of the light
switchable degron in different types of protein. We suggest that the light
switchable degron offers a robust tool to control protein levels and may serves
as a new and significant method for gene- and cell-based therapies.
PMID- 28412350
TI - Patient sample-oriented analysis of gene expression highlights extracellular
signatures in breast cancer progression.
AB - Although a large collection of cancer cell lines are useful surrogates for
patient samples, the physiological relevance of observed molecular phenotypes in
cell lines remains controversial. Because transcriptome data are a representative
set of molecular phenotypes in cancers, we systematically analyzed the
discrepancy of global gene expression profiles between patient samples and cell
lines in breast cancers. While the majority of genes exhibited general
consistency between patient samples and cell lines, the expression of genes in
the categories of extracellular matrix, collagen trimers, receptor activity,
catalytic activity and transporter activity were significantly up-regulated only
in tissue samples. Genes in the extracellular matrix, particularly collagen
trimers, showed a wide variation of expression in tissue, but minimal expression
and variation in cell lines. Further analysis of tissue samples exclusively
revealed that collagen genes exhibited a cancer stage-dependent expressional
variation based on their supramolecular structure. Prognostic collagen biomarkers
associated with survival rate were also readily predicted from tissue-oriented
transcriptome analysis. This study presents the limitations of cell lines and the
exclusive features of tissue samples in terms of functional categories of the
cancer transcriptome.
PMID- 28412351
TI - Effect of ApoA4 on SERPINA3 mediated by nuclear receptors NR4A1 and NR1D1 in
hepatocytes.
AB - ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear.
SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been
shown to be involved in anti-inflammation and associated with a number of human
diseases. In this study, we revealed that ApoA4 stimulates the gene expression of
SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time
dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated
through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the
SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and
RNA interference-mediated NR4A1 or NR1D1 gene knockdown. These data suggests that
ApoA4 transcriptionally induced SERPINA3 expression via NR1D1 and NR4A1. Our
findings may throw light on the function of ApoA4 in inflammatory responses and
acute-phase reactions, as well as the development of SERPINA3 relative diseases.
PMID- 28412352
TI - Knockdown of Nucleostemin in an ovarian cancer SKOV-3 cell line and its effects
on cell malignancy.
AB - Nucleostemin plays an essential role in the proliferation of some stem cells and
cancer cells, but no research has been conducted to assess the link between
Nucleostemin and ovarian cancer. To investigate the role of Nucleostemin in
ovarian cancer tumorigenesis, we generated short hairpin (sh)RNA to knockdown the
expression of the Nucleostemin gene in an ovarian cancer SKOV-3 cell line. We
found that knockdown of this gene led to cell-cycle arrest, as well as to an
increase in apoptosis. In addition, migration and invasion demonstrated
significant inhibition in Nucleostemin-deficient cells. Furthermore, the
knockdown of Nucleostemin dramatically suppressed xenograft progression in BALB/c
nude mice. Our findings suggest that Nucleostemin is associated with malignancy
in an ovarian cancer SKOV-3 cell line.
PMID- 28412353
TI - Crystal structure of RNA polymerase II from Komagataella pastoris.
AB - RNA polymerase II (Pol II) is a 12-subunit protein complex that conducts the
transcription of mRNA and some small RNAs. In this work, the crystal structure of
Pol II from the methylotropic yeast Komagataella pastoris (Pichia pastoris) was
determined. While the structure is highly homologous to that of Pol II from the
budding yeast Saccharomyces cerevisiae, the stalk and clamp modules of the K.
pastoris Pol II displayed large inward rotations, closing the central cleft to a
greater extent than in the known S. cerevisiae Pol II structures. The
conformational differences reflect the inherent flexibilities of the stalk and
the clamp, as additional low-resolution structures of K. pastoris Pol II in
different crystal forms revealed diverse stalk and clamp orientations.
Comparisons with other eukaryotic/archaeal RNA polymerase structures in the
Protein Data Bank revealed the distributions of the stalk and clamp orientations.
The conformational plasticity should be essential for transcriptional functions
and binding various regulatory factors.
PMID- 28412355
TI - Crystal structure of the C-terminal domain of Bacillus subtilis GabR reveals a
closed conformation by gamma-aminobutyric acid binding, inducing transcriptional
activation.
AB - Bacillus subtilis GabR (BsGabR) is involved in the gamma-aminobutyric acid (GABA)
catabolism as a transcriptional regulator, consisting of an N-terminal helix-turn
helix DNA-binding domain and a C-terminal aminotransferase-like (AT-like) domain.
Research on the C-terminal AT-like domain of BsGabR (BsGabR-CTD) has focused on
the interaction with GABA as an effector, but most its functional details remain
unclear. To understand the underlying mechanism, we report the crystal structure
of BsGabR-CTD in complex with pyridoxal 5'-phosphate (PLP) and GABA at 2.0 A
resolution. The structure of ligand-bound BsGabR-CTD revealed two distinct
monomeric states in a homodimer. One subunit is a closed-form containing the PLP
GABA adduct, and the other subunit is a PLP-bound open-form. Our structural
studies provide a detailed mechanism indicating that the open-to-closed
transition by the binding of GABA induces the conformational rearrangement of
BsGabR-CTD, which may trigger the activation of transcription.
PMID- 28412354
TI - Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign
prostatic hyperplasia.
AB - Several studies have implicated estrogen and the estrogen receptor (ER) in the
pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism
underlying this effect remains elusive. In the present study, we demonstrated
that estrogen (17beta-estradiol, or E2)-induced activation of the G protein
coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic
reticulum, increased the mitochondrial Ca2+ concentration, and thus induced
prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist
G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C
(PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by
treatment with the GPR30 antagonist G15. The release of cytochrome c and
activation of caspase-3 in response to GPR30 activation were observed. Data
generated from the analysis of animal models and human clinical samples indicate
that treatment with the GPR30 agonist relieves testosterone propionate (TP)
induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is
negatively associated with prostate volume. On the basis of these results, we
propose a novel regulatory mechanism whereby estrogen induces the apoptosis of
PECs via GPR30 activation. Inhibition of this activation is predicted to lead to
abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.
PMID- 28412357
TI - Crystal structure of Pseudomonas aeruginosa N-acetyltransferase PA4534.
AB - The GCN5-related N-acetyltransferase (GNAT) superfamily includes a large and
diverse group of enzymes that catalyzes the transfer of an acetyl group from
acetyl coenzyme A (Ac-CoA) to the amine group of a substrate. Substrates include
protein N-terminus, lysine of histone tails, and other small molecules such as
aminoglycoside, serotonin, and glucose-6-phosphate. GNAT superfamily of proteins
is involved in many physiologically important reactions in eukaryotes and
prokaryotes. However, functions of many GNATs remain unknown and PA4534 is one of
those uncharacterized GNAT proteins from Pseudomonas aeruginosa. To investigate
functions of the PA4534, we determined the apo and Ac-CoA bound PA4534
structures. Our structures showed that PA4534 shared common characteristic
structures with other GNAT family N-acetyltransferases and contained a potential
substrate binding tunnel close to the bound Ac-CoA.
PMID- 28412356
TI - Leptomycin B alters the subcellular distribution of CRM1 (Exportin 1).
AB - CRM1 (chromosome maintenance region 1, Exportin 1) binds to nuclear export
signals and is required for nucleocytoplasmic transport of a large variety of
proteins and RNP complexes. Leptomycin B (LMB), the first specific inhibitor of
CRM1 identified, binds covalently to cysteine 528 in the nuclear export signal
binding region of CRM1 leading to the inhibition of protein nuclear export.
Although the biochemical mechanisms of action of CRM1 inhibitors such as LMB are
well studied, the subcellular effects of inhibition on CRM1 are unknown. We have
found that LMB causes CRM1 to redistribute from the nucleus to the cytoplasm in
A549 cells. A significant decrease in nuclear CRM1 coupled with an increase in
cytoplasmic CRM1 was sustained for up to 4 h, while there was no change in total
CRM1 protein in fractionated cells. Cells expressing an LMB insensitive HA-tagged
CRM1-C528S protein were unaffected by LMB treatment, whereas HA-tagged wildtype
CRM1 redistributed from the nucleus to the cytoplasm with LMB treatment, similar
to endogenous CRM1. GFP-tagged CRM1 protein microinjected into the cytoplasm of
A549 cells distributed throughout the cell in untreated cells remained primarily
cytoplasmic in LMB-treated cells. Upon nuclear microinjection, GFP-CRM1
translocated to and accumulated in the cytoplasm of LMB-treated cells. Thus, LMB
binds to CRM1 and causes its redistribution to the cytoplasm by inhibiting its
nuclear import. Decreasing the nuclear availability of CRM1 likely contributes to
the accumulation of CRM1 cargo proteins in the nucleus, suggesting a new
mechanism of action for LMB.
PMID- 28412358
TI - Impact of G-quadruplex loop conformation in the PITX1 mRNA on protein and small
molecule interaction.
AB - Intramolecular G-quadruplexes (G4s) are G-rich nucleic acid structures that fold
back on themselves via interrupting loops to create stacked planar G-tetrads, in
which four guanine bases associate via Hoogsteen hydrogen bonding. The G4
structure is further stabilized by monovalent cations centered between the
stacked tetrads. The G-tetrad face on the top and bottom planes of G4s are often
the site of interaction with proteins and small molecules. To investigate the
potential impact of interrupting loops on both G4 structure and interaction with
proteins/small molecules, we characterized a specific G4 from the 3'-UTR of PITX1
mRNA that contains loops of 6 nucleotides using biophysical approaches. We then
introduced mutations to specific loops to determine the impact on G4 structure
and the ability to interact with both proteins and a G4-specific ligand. Our
results suggest that mutation of a specific loop both affects the global G4
structure and impacts the ability to interact with a G4 binding protein and small
molecule ligand.
PMID- 28412359
TI - Potentiation of docetaxel sensitivity by miR-638 via regulation of STARD10
pathway in human breast cancer cells.
AB - Acquired resistance to classical chemotherapeutics such as docetaxel (DTX)
remains a critical challenge in breast cancer (BCa) treatment. Epigenetic
modification by microRNAs (miRNAs) has been shown to play a crucial role in
cancer drug resistance. Previous study, using human drug-resistant BCa tissues,
has identified miR-638 as one of the most down-regulated miRNAs, but its exact
roles and underlying mechanisms during the pathogenesis of chemoresistance remain
to be determined. In the current study, we found that miR-638 expression was
significantly down-regulated in clinical DTX-resistant BCa tissues compared to
that in DTX-sensitive BCa tissues. By using the previously established DTX
resistant MCF-7 cells (MCF-7/R), we also confirmed that chemoresistant cells
displayed decreased levels of miR-638. To provide the direct functional evidence,
we inhibited and overexpressed miR-638 in different cell lines. Thereby, the
cells were rendered more resistant or susceptible to DTX treatment.
Mechanistically, the lipid-binding protein STARD10 was identified as a miR-638
target mediating the DTX-resistance. Hence, we provide a molecular explanation
for acquired resistance to DTX that is caused by the miR-638 deficiency and
subsequent STARD10 upregulation. In consequence, alteration of miR-638/STARD10
cascade may represent an attractive strategy in future adjuvant therapy along
with DTX chemotherapy.
PMID- 28412360
TI - In-house made nucleofection buffer for efficient and cost effective transfection
of RAW 264.7 macrophages.
AB - Electroporation is the most widely employed method of gene transfer into
macrophages which are hard to transfect. RAW 264.7 is a widely used cell line for
studying macrophage responses. Electroporation of RAW 264.7 cells with commercial
reagents although very efficient is expensive necessitating the development of
cost effective alternatives. In this study, we have formulated an economical
electroporation buffer for electroporation of RAW 264.7 cells compatible with
commercial nucleofector apparatus. We observed that supplementation of membrane
fusogenic agents such as Ficoll, PEG and membrane resealing agent, poloxamer
P188, enhanced the transfection efficiency of macrophages to a level comparable
to the commercially available solutions thereby providing us a cost effective
solution for genetic manipulation of macrophages especially in large numbers.
PMID- 28412361
TI - Structural insights into the binding mechanism of IDO1 with hydroxylamidine based
inhibitor INCB14943.
AB - IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive
enzyme, has attracted growing attention as a potential target for cancer
immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360
analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical
trials for treatment of various types of human cancer. Here, we determined the co
crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode.
INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen. Further
analysis also reveals that a halogen bonding interaction between the chlorine
atom (3-Cl) of INCB14943 and the sulphur atom of C129 significantly improves the
inhibition activity against IDO1. Comparing with the other reported inhibitors,
the oxime nitrogen and halogen bond interaction are identified as the unique
features of INCB14943 among the IDO1 inhibitors. Thus, our study provides novel
insights into the interaction between a small molecule inhibitor INCB14943 and
IDO1 protein. The structural information will facilitate future IDO1 inhibitor
design.
PMID- 28412362
TI - Probing the acidic residue within the integrin binding site of laminin-511 that
interacts with the metal ion-dependent adhesion site of alpha6beta1 integrin.
AB - Laminins are major cell-adhesive proteins of basement membranes that interact
with integrins in a divalent cation-dependent manner. Laminin-511 consists of
alpha5, beta1, and gamma1 chains, of which three laminin globular domains of the
alpha5 chain (alpha5/LG1-3) and a Glu residue in the C-terminal tail of chain
gamma1 (gamma1-Glu1607) are required for binding to integrins. However, it
remains unsettled whether the Glu residue in the gamma1 tail is involved in
integrin binding by coordinating the metal ion in the metal ion-dependent
adhesion site of beta1 integrin (beta1-MIDAS), or by stabilizing the conformation
of alpha5/LG1-3. To address this issue, we examined whether alpha5/LG1-3 contain
an acidic residue required for integrin binding that is as critical as the Glu
residue in the gamma1 tail; to achieve this, we undertook exhaustive alanine
substitutions of the 54 acidic residues present in alpha5/LG1-3 of the E8
fragment of laminin-511 (LM511E8). Most of the alanine mutants possessed
alpha6beta1 integrin binding activities comparable with wild-type LM511E8.
Alanine substitution for alpha5-Asp3198 and Asp3219 caused mild reduction in
integrin binding activity, and that for alpha5-Asp3218 caused severe reduction,
possibly resulting from conformational perturbation of alpha5/LG1-3. When alpha5
Asp3218 was substituted with asparagine, the resulting mutant possessed
significant binding activity to alpha6beta1 integrin, indicating that alpha5
Asp3218 is not directly involved in integrin binding through coordination with
the metal ion in beta1-MIDAS. Given that substitution of gamma1-Glu1607 with
glutamine nullified the binding activity to alpha6beta1 integrin, these results,
taken together, support the possibility that the critical acidic residue
coordinating the metal ion in beta1-MIDAS is Glu1607 in the gamma1 tail, but no
such residue is present in alpha5/LG1-3.
PMID- 28412363
TI - WDR5 positively regulates p53 stability by inhibiting p53 ubiquitination.
AB - WD40 repeat protein WDR5 is a core component of the Set/MLL histone
methyltransferase complex which catalyzes histone H3 Lys4 trimethylation and
activates gene transcription in human cells. WDR5 promotes Set/MLL complex
assembly and mediates the complex binding to Lys4-dimethylated histone H3 tail.
Most earlier studies report that WDR5 exerts profound effects on various cellular
and organismal processes mainly through epigenetic regulation of gene
transcription. However, the functions of WDR5 in lung cancer remain largely
unknown. Here, we report that WDR5 positively regulates p53 stability by
inhibiting p53 ubiquitination in human lung cancer A549 cells. Overexpression of
WDR5 dramatically increases p53 protein levels and its half-life in A549 cells,
while depletion of WDR5 with WDR5-specific siRNAs significantly decreases p53
protein levels. We also observe that WDR5 is required for p53 induction in
response to cisplatin treatment. Mechanistically, WDR5 colocalizes with p53 and
inhibits p53 ubiquitination, resulting in p53 stabilization. Consequently,
overexpression of WDR5 induces G1 phase arrest in A549 cells, and knocking down
WDR5 by siRNAs reduces the population at G1 phase. Furthermore, p53 expression
levels is at least in part determined by the p53 positive regulator WDR5 in some
cancer cells. Taken together, these data suggest that WDR5 is directly involved
in p53 signaling pathway. Our studies provide a new insight into WDR5 functions
in A549 cells.
PMID- 28412364
TI - The cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian
cancer cells.
AB - Ovarian cancer is the most lethal gynecologic malignancy, and cisplatin is one of
the first-line chemotherapeutic agents. However, acquired cisplatin resistance
prevents the successful treatment of patients with ovarian cancer. Gap junction
(GJ) and connexin (Cx) are closely related to tumor formation, but the
relationship between cisplatin resistance and GJ or Cx are undetermined. In this
study, we established the cisplatin-resistant human ovarian cancer cell line
A2780-CDDP. Here we showed that cisplatin resistance was correlated to the loss
of GJ and the upregulation of Cx32 expression. Enhancing GJ in A2780-CDDP cells
could increase the apoptotic response to cisplatin treatment. Furthermore,
although Cx32 expression was increased in A2780-CDDP cells, it was more localized
to the cytoplasm rather than in the membrane, and knockdown of Cx32 in A2780-CDDP
cells sensitized them to cisplatin treatment. In summary, Cx32 is involved in
cisplatin resistance, and cytoplasmic Cx32 plays an important role in
chemoresistance.
PMID- 28412365
TI - Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by
affecting the subcellular localization of clock proteins in mammalian cells.
AB - In the eukaryotic circadian clock machinery, negative feedback repression of
CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME
(CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise
regulation of the time-dependent nuclear entry of circadian repressors is crucial
to generating normal circadian rhythms. Here, we sought to identify novel
kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased
screening using red fluorescent protein (RFP)-tagged human kinome expression
plasmids in mammalian cells. Transient expression of human vaccinia-related
kinase 3 (hVRK3) reduced the nuclear presence of mCRY1. hVRK3 expression also
induced alterations in the subcellular localization of other core clock proteins,
including mCRY2, mPER2, and BMAL1. In contrast, the subcellular localization of
mCLK was not changed. Given that singly expressed mCLK mostly resides in the
cytoplasm and that nuclear localization sequence (NLS) mutation of hVRK3
attenuated the effect of hVRK3 co-expression on subcellular localization,
ectopically expressed hVRK3 presumably reduces the retention of proteins in the
nucleus. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and
lengthened the period of the cellular bioluminescence rhythm. Taken together,
these data suggest that VRK3 plays a role in setting the amplitude and period
length of circadian rhythms in mammalian cells.
PMID- 28412366
TI - NANOG gene expression is regulated by the ETS transcription factor ETV4 in human
embryonic carcinoma NCCIT cells.
AB - We demonstrated that ETV4 is a transcriptional activator of the NANOG gene in
human embryonic carcinoma NCCIT cells. The endogenous expression of NANOG and
ETV4 in naive cells was significantly down-regulated upon differentiation and by
shRNA-mediated knockdown of ETV4. NANOG transcription was significantly
upregulated by ETV4 overexpression. A putative ETS binding site (EBS) is present
in the region (-285 to -138) of the proximal promoter. Site-directed mutagenesis
of the putative EBS (-196AGGATT-191) abolished NANOG promoter activity and ETV4
interacted with this putative EBS both in vivo and in vitro. Our data provide the
molecular details of ETV4-mediated NANOG gene expression.
PMID- 28412367
TI - Deciphering antigen-responding antibody repertoires by using next-generation
sequencing and confirming them through antibody-gene synthesis.
AB - Vast diversity and high specificity of antigen recognition by antibodies are
hallmarks of the acquired immune system. Although the molecular mechanisms that
yield the extremely large antibody repertoires are precisely understood,
comprehensive description of the global antibody repertoire generated in
individual bodies has been hindered by the lack of powerful measures. To obtain
holistic understanding of the antibody-repertoire space, we used next-generation
sequencing (NGS) to analyze the deep profiles of naive and antigen-responding
repertoires of the IgM, IgG1, and IgG2c classes formed in individual mice. The
overall landscapes of naive IgM repertoires were almost the same for each mouse,
whereas those of IgG1 and IgG2c differed considerably among naive individuals.
Next, we immunized mice with a model antigen, nitrophenol (NP)-hapten linked to
chicken gamma-globulin (CGG) carrier, and compared the antigen-responding
repertoires in individual mice. To extract the complete antigen response, we
developed an intelligible method for detecting common components of antigen
responding repertoires. The major responding antibodies were IGHV1-72/IGHD1
1/IGHJ2 for NP-hapten and IGHV9-3/IGHD3-1/IGHJ2 for CGG-carrier protein. The
antigen-binding specificities of the identified antibodies were confirmed through
ELISA after antibody-gene synthesis and expression of the corresponding NGS
reads. Thus, we deciphered antigen-responding antibody repertoires by inclusively
analyzing the antibody-repertoire space generated in individual bodies by using
NGS, which avoided inadvertent omission of key antibody repertoires.
PMID- 28412368
TI - HSP90 inhibitor NVP-AUY922 induces cell apoptosis by disruption of the survivin
in papillary thyroid carcinoma cells.
AB - Heat shock protein 90 (HSP90) is a molecular chaperone required for maintaining
the stability and function of signal proteins that plays an important role in
promoting the growth and survival of cancer cells. The incidence of papillary
thyroid carcinoma (PTC) has been increasing in recent years. The effect of the
novel non-geldanamycin HSP90 inhibitor NVP-AUY922 on apoptosis of papillary
thyroid carcinoma cells has not been investigated. The influence of AUY922 on the
survival of PTC cell lines K1 and IHH4 was evaluated. Cell viability was
determined by cell counting kit method. Cell apoptosis was assessed by flow
cytometry and western blotting and the potential mechanism was evaluated by
western blotting and immunoprecipitation. Overexpression plasmid was transfected
by Lipofectamine 2000 method. In K1 and IHH4 cell lines, after the treatment of
AUY922, cell viability decreased, and the proportion of apoptosis cells
increased. AUY922 caused the cleavage of PARP and caspase-3 proteins, and altered
expression of survivin, which was a client protein of HSP90. In AUY922-treated
cells, overexpression of survivin attenuated growth inhibition and cell
apoptosis. The results indicate that AUY922 induces apoptotic cell death in PTC
cells. Moreover, our findings demonstrate that AUY922 induced apoptosis by
downregulating the expression of survivin protein in PTC cells.
PMID- 28412369
TI - Structural basis for ribosome protein S1 interaction with RNA in trans
translation of Mycobacterium tuberculosis.
AB - Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a
significant role in translation and trans-translation. In Mycobacterium
tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of
pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans
translation. However, the molecular mechanism underlying the interaction of
MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C
terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD.
NMR titration analysis revealed that the RNA binding sites on MtRpsACTD are
mainly located in the beta2, beta3 and beta5 strands and the adjacent L3 loop of
the S1 domain. Fluorescence experiments determined the MtRpsACTD binding to RNAs
are in the micromolar affinity range. Sequence analysis also revealed conserved
residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322,
I323, R357 and I358 were verified to be the key residues influencing the
interaction between MtRpsACTD and pre-sMLD. Molecular docking further confirmed
that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein
RNA interaction, through charged interaction and hydrogen bonds. The results will
be beneficial for designing new anti-tuberculosis drugs.
PMID- 28412370
TI - Suppression of adenosine monophosphate-activated protein kinase selectively
triggers apoptosis in activated T cells and ameliorates immune diseases.
AB - Deficient apoptosis of activated T cells can result in immunological disorders.
Molecules associated with energy and metabolisms are suggested to be involved in
pathogenesis of immune diseases, but remain uninvestigated. In the present study
we reported that glibenclamide exerted a new pharmacological effect on
inflammatory responses by selectively triggering apoptosis of activated T cells.
Glibenclamide demonstrated an inhibition on activated T lymphocytes, whereas
showed no toxicity in the naive cells. This effect was mainly related with its
ability to facilitate apoptosis in activated T cells with an up-regulation of
cleaved-caspases and cleaved-PARP. Glibenclamide enhanced Fas expression and
suppressed the expression of antiapoptotic cellular FLICE-inhibitory protein. The
underlying mechanism of glibenclamide was not associated with its classical
inhibitory effect on ATP-sensitive potassium channels, but due to a unique
suppression on the phosphorylation of 5' adenosine monophosphate-activated
protein kinase, which was augmented during T cell activation. An in vivo
experiment further demonstrated that glibenclamide ameliorated T-cell-mediated
contact hypersensitivity in mice. Altogether, these results suggest that AMPK
inhibition by glibenclamide can regulate the survival and death of T lymphocytes
and be beneficial for the treatment of autoimmune diseases.
PMID- 28412371
TI - The anti-inflammatory effect of tramadol in the temporomandibular joint of rats.
AB - Tramadol is a centrally acting analgesic drug able to prevent nociceptor
sensitization when administered into the temporomandibular joint (TMJ) of rats.
The mechanism underlying the peripheral anti-inflammatory effect of tramadol
remains unknown. This study demonstrated that intra-TMJ injection of tramadol
(500ug/TMJ) was able to inhibit the nociceptive response induced by 1.5% formalin
or 1.5% capsaicin, suggesting that tramadol has an antinociceptive effect, acting
directly on the primary nociceptive neurons activating the nitric oxide/cyclic
guanosine monophosphate signaling pathway. Tramadol also inhibited the
nociceptive response induced by carrageenan (100ug/TMJ) or 5-hydroxytryptamine
(225ug/TMJ) along with inhibition of inflammatory cytokines levels, leukocytes
migration and plasma extravasation. In conclusion, the results demonstrate that
peripheral administration of tramadol has a potential antinociceptive and anti
inflammatory effect. The antinociceptive effect is mediated by activation of the
intracellular nitric oxide/cyclic guanosine monophosphate pathway, at least in
part, independently from the opioid system.
PMID- 28412372
TI - Flavonoids and platelet aggregation: A brief review.
AB - Platelets are small anucleated fragments derived from a megakaryocyte precursor.
Platelets play a key role in many physiological functions especially in
hemostasis and wound healing processes in order to maintain the integrity of the
circulatory system. In addition, activated platelets release cytokines and
chemokines which modulate the immune response and, in some cases of
hyperactivation, they could be associated to the pathogenesis of inflammatory
diseases. Flavonoids are polyphenolic compounds ubiquosly found in plants known
to be potent antioxidants with positive effects against diverse diseases such as
cancer, neurodegenerative or cardiovascular disease. It has been reported that
some flavonoids possess anti-platelet aggregation effects though different
pathways, being the inhibition of the arachidonic acid-based pathway the most
representative mechanism of action. In the present review, the main sources of
flavonoids, as well as their bioavailability and metabolism are summarized.
Moreover, the available data about the anti-aggregation effects of flavonoids and
the different mechanisms of action that has been proposed until now are also
discussed.
PMID- 28412373
TI - Mechanistic evaluation of tapentadol in reducing the pain perception using in
vivo brain and spinal cord microdialysis in rats.
AB - Role of monoamine neurotransmitters in the modulation of emotional and pain
processing in spinal cord and brain regions is not well known. Tapentadol, a
norepinephrine reuptake inhibitor with u-opioid receptor agonistic activity has
recently been introduced for the treatment of moderate to severe pain. The
objective of the present study was to examine the effects of tapentadol on
modulation of monoamines in the prefrontal cortex and dorsal horn using brain
microdialysis. Tapentadol was administered intraperitoneally at 4.64-21.5mg/kg to
male Wistar rats. Based on these results, 10mg/kg i.p. was chosen for spinal
microdialysis in freely moving rats. Tapentadol produced significant and dose
dependent increase in cortical dopamine and norepinephrine levels with mean
maximum increase of 600% and 300%, respectively. Treatment had no effect on
cortical serotonin levels. In the dorsal horn, serotonin, dopamine and
norepinephrine levels were significantly increased with mean maximum increases of
220%, 190% and 280%, respectively. Although the density of dopamine transporter
is low in cortex, the increase of dopamine and norepinephrine levels in cortex
could be mediated through the inhibition of norepinephrine transporter. In the
dorsal horn, increase in norepinephrine levels could be due to inhibition of
norepinephrine transporter in the spinal cord. Whereas, activation of opioids
receptors in non-spinal regions might be responsible for increase in dopamine and
serotonin levels. The results from current investigation suggest that clinical
efficacy of tapentadol in neuropathic pain is mediated through the enhanced
monoaminergic neurotransmission in the spinal cord and regions involved with
emotional processing in brain.
PMID- 28412374
TI - A novel mitochondrial ATP6 frameshift mutation causing isolated complex V
deficiency, ataxia and encephalomyopathy.
AB - We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4
year-old girl associated with ataxia, microcephaly, developmental delay and
intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene
was confirmed in the patient's skeletal muscle and blood. The mutation was not
detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic
and oxymetric analysis of the mitochondrial respiratory system in the patients'
skeletal muscle and skin fibroblasts demonstrated an isolated complex V
deficiency. Native PAGE with subsequent immunoblotting for complex V revealed
impaired complex V assembly and accumulation of ATPase subcomplexes. Whilst
northern blotting confirmed equal presence of ATP8/6 mRNA, metabolic 35S
labelling of mitochondrial translation products showed a severe depletion of the
ATP6 protein together with aberrant translation product accumulation. In
conclusion, this novel isolated complex V defect expands the clinical and genetic
spectrum of mitochondrial defects of complex V deficiency. Furthermore, this work
confirms the benefit of native PAGE as an additional diagnostic method for the
identification of OXPHOS defects, as the presence of complex V subcomplexes is
associated with pathogenic mutations of mtDNA.
PMID- 28412377
TI - What Can we Learn (and What Can't we Learn) from Observational Studies of
Adolescent Varicocele Treatment?
PMID- 28412378
TI - Project management: importance for diagnostic laboratories.
AB - BACKGROUND: The need for diagnostic laboratories to improve both quality and
productivity alongside personnel shortages incite laboratory managers to
constantly optimize laboratory workflows, organization, and technology. These
continuous modifications of the laboratories should be conducted using efficient
project and change management approaches to maximize the opportunities for
successful completion of the project. AIM: This review aims at presenting a
general overview of project management with an emphasis on selected critical
aspects. SOURCES: Conventional project management tools and models, such as
HERMES, described in the literature, associated personal experience, and
educational courses on management have been used to illustrate this review.
CONTENT: This review presents general guidelines of project management and
highlights their importance for microbiology diagnostic laboratories. As an
example, some critical aspects of project management will be illustrated with a
project of automation, as experienced at the laboratories of bacteriology and
hygiene of the University Hospital of Lausanne. It is important to define clearly
beforehand the objective of a project, its perimeter, its costs, and its time
frame including precise duration estimates of each step. Then, a project
management plan including explanations and descriptions on how to manage,
execute, and control the project is necessary to continuously monitor the
progression of a project to achieve its defined goals. Moreover, a thorough risk
analysis with contingency and mitigation measures should be performed at each
phase of a project to minimize the impact of project failures. IMPLICATIONS: The
increasing complexities of modern laboratories mean clinical microbiologists must
use several management tools including project and change management to improve
the outcome of major projects and activities.
PMID- 28412379
TI - Challenges of measles and rubella laboratory diagnostic in the era of
elimination.
AB - The Member States of the WHO European Region adopted the goal of measles and
rubella elimination more than 10 years ago, but so far only 21 of 53 countries
have reached this target. Laboratory investigation of suspected cases is
essential to support disease elimination efforts. Therefore, WHO maintains a
network of accredited laboratories providing high-quality testing. Laboratory
investigation heavily relies on specific IgM serology and increasingly on virus
detection by reverse transcription (RT)-PCR, but other methods such as IgG
avidity testing and genetic characterization of virus strains have gained in
importance. In elimination settings, often few samples from suspected cases are
available for testing, but testing proficiency must be maintained. The predictive
value of an IgM-positive result decreases and other rash-fever disease
aetiologies become more important. In addition, cases with a rash after
measles/rubella vaccination or with mild disease after waning of vaccine-induced
antibodies are seen more often. Thus, it is necessary to perform comprehensive
and potentially time-consuming and costly investigations of every suspected case
using quality-controlled laboratory methods. At the same time rapid feedback to
public health officers is required for timely interventions. The introduction of
new laboratory methods for comprehensive case investigations requires training of
staff under the supervision of WHO-accredited reference laboratories and the
definition of appropriate test algorithms. Clinical, laboratory, and
epidemiological data are essential for final case classification and
investigation of chains of transmission in the endgame of measles and rubella
elimination.
PMID- 28412380
TI - Colonization by multidrug-resistant organisms in long-term care facilities in
Italy: a point-prevalence study.
AB - OBJECTIVES: To determine prevalence and risk factors for colonization by
multidrug-resistant organisms (MDROs) in long-term care facility (LTCF) residents
in Italy. Genotypes of MDRO isolates were investigated. METHODS: A point
prevalence study was conducted at 12 LTCFs located in four Italian cities (2
February to 14 March 2015). Rectal swabs, faeces and nasal/auxiliary swabs were
cultured for extended-spectrum beta-lactamase (ESBL)- and/or carbapenemase
producing Enterobacteriaceae, Clostridium difficile and methicillin-resistant
Staphylococcus aureus (MRSA) respectively. Antimicrobial susceptibility testing,
detection of ESBL and/or carbapenemase genes and molecular typing of MDROs were
performed. Risk factors for colonization were determined by univariate and
multivariate analysis. RESULTS: A total of 489 LTCF residents aged >=65 years
were enrolled. The prevalence of colonization by ESBL-producing
Enterobacteriaceae, MRSA and C. difficile was 57.3% (279/487), 17.2% (84/487) and
5.1% (21/409) respectively. Carriage rate of carbapenemase-producing
Enterobacteriaceae was 1% (5/487). Being bedridden was a common independent risk
factor for colonization by all MDROs, although risk factors specific for each
MDRO were identified. ESBL-producing Escherichia coli carriage was associated
with the sequence type (ST) 131-H30 subclone, but other minor STs predominated in
individual LTCF or in LTCFs located in the same city, suggesting a role for
intrafacility or local transmission. Similarly, MRSA from LTCF residents belonged
to the same spa types/ST clones (t008/ST8 and t032/ST22) commonly found in
Italian acute-care hospitals, but infrequent spa types were recovered in
individual LTCFs. The prevalent C. difficile PCR ribotypes were 356/607 and 018,
both common in Italian acute-care hospitals. CONCLUSIONS: MDRO colonization is
common among residents in Italian LTCFs.
PMID- 28412381
TI - Optimal efficacy of interferon-free HCV retreatment after protease inhibitor
failure in real life.
AB - OBJECTIVES: First-generation protease-inhibitors (PIs) have suboptimal efficacy
in GT-1 patients with advanced liver disease, and patients experiencing treatment
failure may require urgent retreatment. Our objective was to analyse the real
life efficacy of interferon (IFN)-free retreatment after PI-failure, and the role
of genotypic-resistance-testing (GRT) in guiding retreatment choice. METHODS: In
this multi-centre observational study, patients retreated with IFN-free regimens
after first-generation PI-failure (telaprevir-boceprevir-simeprevir) were
included. Sustained-virological-response (SVR) was evaluated at week 12 of follow
up. GRT was performed by population-sequencing. RESULTS: After PI-failure, 121
patients (cirrhotic=86.8%) were retreated following three different strategies:
A) with 'GRT-guided' regimens (N=18); B) with 'AASLD/EASL recommended, not GRT
guided' regimens (N=72); C) with 'not recommended, not GRT-guided' regimens
(N=31). Overall SVR rate was 91%, but all 18 patients treated with 'GRT-guided'
regimens reached SVR (100%), despite heterogeneity in treatment duration, use of
PI and ribavirin, versus 68/72 patients (94.4%) receiving 'AASLD/EASL
recommended, not GRT-guided' regimens. SVR was strongly reduced (77.4%) among the
31 patients who received a 'not recommended, not GRT-guided regimen' (p <0.01).
Among 37 patients retreated with a PI, SVR rate was 89.2% (33/37). Four GT-1a
cirrhotic patients failed an option (C) simeprevir-containing treatment; three
out of four had a baseline R155K NS3-RAS. All seven patients treated with
paritaprevir-containing regimens reached SVR, regardless of treatment duration
and performance of a baseline-GRT. CONCLUSION: Retreatment of PI-experienced
patients can induce maximal SVR rates in real life. Baseline-GRT could help to
optimize retreatment strategy, allowing PIs to be reconsidered when chosen after
a RASs evaluation.
PMID- 28412382
TI - Use of nebulized antimicrobials for the treatment of respiratory infections in
invasively mechanically ventilated adults: a position paper from the European
Society of Clinical Microbiology and Infectious Diseases.
AB - With an established role in cystic fibrosis and bronchiectasis, nebulized
antibiotics are increasingly being used to treat respiratory infections in
critically ill invasively mechanically ventilated adult patients. Although there
is limited evidence describing their efficacy and safety, in an era when there is
a need for new strategies to enhance antibiotic effectiveness because of a
shortage of new agents and increases in antibiotic resistance, the potential of
nebulization of antibiotics to optimize therapy is considered of high interest,
particularly in patients infected with multidrug-resistant pathogens. This
Position Paper of the European Society of Clinical Microbiology and Infectious
Diseases provides recommendations based on the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) methodology regarding the use of
nebulized antibiotics in invasively mechanically ventilated adults, based on a
systematic review and meta-analysis of the existing literature (last search July
2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in
clinical practice, due to a weak level of evidence of their efficacy and the high
potential for underestimated risks of adverse events (particularly, respiratory
complications). Higher-quality evidence is urgently needed to inform clinical
practice. Priorities of future research are detailed in the second part of the
Position Paper as guidance for researchers in this field. In particular, the
panel identified an urgent need for randomized clinical trials of nebulized
antibiotic therapy as part of a substitution approach to treatment of pneumonia
due to multidrug-resistant pathogens.
PMID- 28412384
TI - Molecular epidemiology of penicillinase-producing Neisseria gonorrhoeae isolates
in France.
AB - OBJECTIVES: Characterizing the molecular epidemiology of antibiotic resistance is
crucial for a better understanding of the evolution and spread of resistance in
Neisseria gonorrhoeae. Here, we examine the molecular epidemiology of
penicillinase-producing N. gonorrhoeae (PPNG) isolates in France. METHODS: We
investigated 176 PPNG isolates collected between 2010 and 2012 by the National
Reference Centre in France. Genotyping was performed using the NG-MAST technique,
blaTEM genes were Sanger-sequenced, and plasmids were characterized by PCR
typing. RESULTS: We revealed the existence of four major clusters representing
about one-third of PPNG circulating in France. These clusters were related to
ST1479 (18/176, 10.2%), to ST1582 (15/176, 8.5%), to ST8922 (10/176, 5.6%), and
to ST1285 (9/176, 5.1%). Wild-type TEM-1 was identified in 151 (151/176, 85.8%)
PPNG isolates, and TEM-1 variants were mostly represented by the M182T mutation
(14/176, 8%), followed by P14S/L (8/176, 4.5%), G228S (2/176, 1.1%), and Q269K
(1/176, 0.6%). The blaTEM genes were carried by African (157/176, 89.2%), Asian
(13/176, 7.4%), and Toronto/Rio (6/176, 3.4%) plasmids. The M182T variants were
found in various genetic backgrounds, whereas the P14S variants were disseminated
clonally. The G228S and Q269K variants belong to one of the four major clusters
of PPNG, which suggests a recent de novo emergence of these mutations.
CONCLUSIONS: Our results show that approximately one-third of the penicillinase
producing N. gonorrhoeae isolates in France belong to one of four major clusters
and that the spread of the different TEM variants is associated with distinct
patterns of molecular epidemiology.
PMID- 28412383
TI - A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM
joint study.
AB - OBJECTIVES: A prospective international multicentre surveillance study was
conducted to investigate the prevalence and amphotericin B susceptibility of
Aspergillus terreus species complex infections. METHODS: A total of 370 cases
from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus
species complex among the investigated patients with mould-positive cultures was
5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8
mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide
spectrum of aspergillosis and the majority of cryptic species display high
amphotericin B MICs.
PMID- 28412385
TI - Eliminating measles and rubella in Europe.
PMID- 28412386
TI - Characterization of rodent constitutively active estrogen receptor alpha variants
and their constitutive transactivation mechanisms.
AB - Estrogen receptor alpha (ERalpha) mRNAs exhibit remarkable heterogeneity owing to
complicated alternative splicing. Some encode C-terminally-truncated ERalpha
proteins, which display ligand-independent transactivation or dominant-negative
activity. We previously characterized C-terminally-truncated ERalpha mRNA
variants with cryptic sequences in humans and mice, and demonstrated that helices
in the ligand-binding domains (LBDs) of ERalpha variants contribute to ligand
independent transcriptional activity. However, existence of non-conventional
coding exons and generation of constitutively active ERalpha variants have
remained to be examined in rats. To comparatively analyze modular organization
and splicing profiles of the ERalpha genes, the range of C-terminally-truncated
ERalpha variants was explored in rats and mice using rapid amplification of cDNA
ends and RT-PCR cloning. Furthermore, their functions were determined in
transiently transfected cells using expression constructs and luciferase reporter
assays. Multiple cryptic exons and C-terminally-truncated ERalpha variant mRNAs
were identified in rats and mice. Naturally occurring and artificially truncated
variants/constructs lacking helix 5 potentially exhibited gain-of-function in
transfected cells. Although cryptic exons and splicing profiles were poorly
conserved among humans, mice, and rats, constitutively active variants were
generated from the ERalpha genes. Moreover, the primary mechanism of ligand
independent activation by C-terminally-truncated ERalpha variants is C-terminus
to helix 5 deletion in the LBD. This comparative study documented the complexity
of ERalpha genes, mRNAs, and proteins, and further determined the underlying
structural basis of ligand-independent activation by C-terminally-truncated
ERalpha variants.
PMID- 28412387
TI - Germ cells regulate 3-hydroxybutyrate production in rat Sertoli cells.
AB - Paracrine regulation of Sertoli cell function by germ cells is an outstanding
characteristic of testicular physiology. It has been demonstrated that Sertoli
cells produce ketone bodies and that germ cells may use them as energy source.
The aim of the study was to analyze a possible regulation by germ cells of
ketogenesis in Sertoli cells. Cultures of Sertoli cells (SC) obtained from 31-day
old rats were co-cultured with germ cells (GC). The results presented herein show
that the presence of GC stimulated 3-hydroxybutyrate production and increased
mRNA levels of two enzymes involved in ketogenesis-carnitine palmitoyltransferase
1a (CPT1a) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (mHMGCoA) synthase-
in SC. Additionally, GC increased monocarboxylate transporter 4 (Mct4) expression
in SC, a transporter involved in ketone bodies exit. To evaluate if the observed
effects might be mediated by soluble factors, SC cultures were incubated with
germinal cell-conditioned medium (GCCM) or with two growth factors, bFGF and
IGF1, which are known to be secreted by GC. We observed that GCCM and bFGF
stimulated ketone bodies production but that IGF1 did not modify it. Also, we
observed that GCCM and bFGF increased Cpt1a and Mct4 mRNA levels. In summary,
results presented herein demonstrate that Sertoli cells are able to produce
ketone bodies and that its production is regulated in a paracrine way by germ
cells. This study adds new information about communication between Sertoli cells
and developing germ cells.
PMID- 28412388
TI - Prolactin modulates luteal activity in the short-nosed fruit bat, Cynopterus
sphinx during delayed embryonic development.
AB - The aim of this study was to evaluate the role of prolactin as a modulator of
luteal steroidogenesis during the period of delayed embryonic development in
Cynopterus sphinx. A marked decline in circulating prolactin levels was noted
during the months of November through December coinciding with the period of
decreased serum progesterone and delayed embryonic development. The seasonal
changes in serum prolactin levels correlated positively with circulating
progesterone (P) level, but inversely with circulating melatonin level during
first pregnancy showing delayed development in Cynopterus sphinx. The results
also showed decreased expression of prolactin receptor-short form (PRL-RS) both
in the corpus luteum and in the utero-embryonic unit during the period of delayed
embryonic development. Bats treated in vivo with prolactin during the period of
delayed development showed significant increase in serum progesterone and
estradiol levels together with significant increase in the expression of PRL-RS,
luteinizing hormone receptor (LH-R), steroidogenic acute receptor protein (STAR)
and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the ovary. Prolactin
stimulated ovarian angiogenesis (vascular endothelial growth factor) and cell
survival (B-cell lymphoma 2) in vivo. Significant increases in ovarian
progesterone production and the expression of prolactin-receptor, LH-R, STAR and
3beta-HSD proteins were noted following the exposure of LH or prolactin in vitro
during the delayed period. In conclusion, short-day associated increased
melatonin level may be responsible for decreased prolactin release during
November-December. The decline in prolactin level might play a role in
suppressing P and estradiol-17beta (E2) estradiol levels thereby causing delayed
embryonic development in C. sphinx.
PMID- 28412389
TI - Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic
Stents.
AB - BACKGROUND: Recent evidence suggests that bioresorbable vascular scaffolds (BVS)
are associated with an excess of thrombotic complications compared with metallic
everolimus-eluting stents (EES). OBJECTIVES: This study sought to investigate the
comparative effectiveness of the Food and Drug Administration-approved BVS versus
metallic EES in patients undergoing percutaneous coronary intervention at longest
available follow-up. METHODS: The authors searched MEDLINE, Scopus, and web
sources for randomized trials comparing BVS and EES. The primary efficacy and
safety endpoints were target lesion failure and definite or probable stent
thrombosis, respectively. RESULTS: Seven trials were included: in sum, 5,583
patients were randomized to receive either the study BVS (n = 3,261) or the EES
(n = 2,322). Median time of follow-up was 2 years (range 2 to 3 years). Compared
with metallic EES, risk of target lesion failure (9.6% vs. 7.2%; absolute risk
difference: +2.4%; risk ratio: 1.32; 95% confidence interval: 1.10 to 1.59;
number needed to harm: 41; p = 0.003; I2 = 0%) and stent thrombosis (2.4% vs.
0.7%; absolute risk difference: +1.7%; risk ratio: 3.15; 95% confidence interval:
1.87 to 5.30; number needed to harm: 60; p < 0.0001; I2 = 0%) were both
significantly higher with BVS. There were no significant differences in all-cause
or cardiovascular mortality between groups. The increased risk for ST associated
with BVS was concordant across the early (<30 days), late (30 days to 1 year),
and very late (>1 year) periods (pinteraction = 0.49). CONCLUSIONS: Compared with
metallic EES, the BVS appears to be associated with both lower efficacy and
higher thrombotic risk over time. (Bioresorbable vascular scaffold compare to
everolimus stents in long term follow up; CRD42017059993).
PMID- 28412390
TI - First-Generation Bioresorbable Vascular Scaffolds: Disappearing Stents or
Disappearing Evidence?
PMID- 28412391
TI - Moving toward endotypes in atopic dermatitis: Identification of patient clusters
based on serum biomarker analysis.
AB - BACKGROUND: Atopic dermatitis (AD) is a complex, chronic, inflammatory skin
disease with a diverse clinical presentation. However, it is unclear whether this
diversity exists at a biological level. OBJECTIVE: We sought to test the
hypothesis that AD is heterogeneous at the biological level of individual
inflammatory mediators. METHODS: Sera from 193 adult patients with moderate-to
severe AD (six area, six sign atopic dermatitis [SASSAD] score: geometric mean,
22.3 [95% CI, 21.3-23.3] and 39.1 [95% CI, 37.5-40.9], respectively) and 30
healthy control subjects without AD were analyzed for 147 serum mediators, total
IgE levels, and 130 allergen-specific IgE levels. Population heterogeneity was
assessed by using principal component analysis, followed by unsupervised k-means
cluster analysis of the principal components. RESULTS: Patients with AD showed
pronounced evidence of inflammation compared with healthy control subjects.
Principal component analysis of data on sera from patients with AD revealed the
presence of 4 potential clusters. Fifty-seven principal components described
approximately 90% of the variance. Unsupervised k-means cluster analysis of the
57 largest principal components delivered 4 distinct clusters of patients with
AD. Cluster 1 had high SASSAD scores and body surface areas with the highest
levels of pulmonary and activation-regulated chemokine, tissue inhibitor of
metalloproteinases 1, and soluble CD14. Cluster 2 had low SASSAD scores with the
lowest levels of IFN-alpha, tissue inhibitor of metalloproteinases 1, and
vascular endothelial growth factor. Cluster 3 had high SASSAD scores with the
lowest levels of IFN-beta, IL-1, and epithelial cytokines. Cluster 4 had low
SASSAD scores but the highest levels of the inflammatory markers IL-1, IL-4, IL
13, and thymic stromal lymphopoietin. CONCLUSION: AD is a heterogeneous disease
both clinically and biologically. Four distinct clusters of patients with AD have
been identified that could represent endotypes with unique biological mechanisms.
Elucidation of these endotypes warrants further investigation and will require
future intervention trials with specific agents, such as biologics.
PMID- 28412392
TI - Diminished airway macrophage expression of the Axl receptor tyrosine kinase is
associated with defective efferocytosis in asthma.
PMID- 28412393
TI - Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein
kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway, which is
counterregulated by autophagy.
AB - BACKGROUND: Eosinophils are a subset of granulocytes that can be involved in the
pathogenesis of different diseases, including allergy. Their effector functions
are closely linked to their cytotoxic granule proteins. Release takes place
through several different mechanisms, one of which is cytolysis, which is
associated with release of intact granules, so-called clusters of free eosinophil
granules. The mechanism underlying this activation-induced form of cell death in
eosinophils has remained unclear. OBJECTIVE: We aimed to elucidate the molecular
mechanism of eosinophil cytolysis. METHODS: Isolated blood eosinophils were
incubated on glass coverslips coated with intravenous immunoglobulin and inactive
complement component 3b. A morphologic characterization of the distinct stages of
the proposed cascade was addressed by means of time-lapse automated fluorescence
microscopy, electron microscopy, and immunohistochemistry. Experiments with
pharmacologic inhibitors were performed to elucidate the sequence of events
within the cascade. Tissue samples of patients with eosinophilic skin diseases or
eosinophilic esophagitis were used for in vivo analyses. RESULTS: After
eosinophil adhesion, we observed reactive oxygen species production, early
degranulation, and granule fusion processes, leading to a distinct morphology
exhibiting cytoplasmic vacuolization and, finally, cytolysis. Using a
pharmacologic approach, we demonstrate the presence of a receptor-interacting
protein kinase 3 (RIPK3)-mixed lineage kinase-like (MLKL) signaling pathway in
eosinophils, which, after its activation, leads to the production of high levels
of reactive oxygen species in a p38 mitogen-activated protein kinase and
phosphatidylinositol 3'-kinase-dependent manner. All these steps are required for
cytoplasmic vacuolization and subsequent cytolysis to occur. Interestingly,
triggering cytolysis is associated with an induction of autophagy in eosinophils,
and additional stimulation of autophagy by means of pharmacologic inhibition of
the mechanistic target of rapamycin counterregulates cell death. Moreover, MLKL
phosphorylation, cytoplasmic vacuolization, and cytolysis were observed in
eosinophils under in vivo inflammatory conditions. CONCLUSION: We report that
adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent
necroptosis, which can be counterregulated by autophagy.
PMID- 28412394
TI - Water-soluble chitosan inhibits nerve growth factor and attenuates allergic
inflammation in mite allergen-induced allergic rhinitis.
PMID- 28412395
TI - Severe asthma: Differential chemokine response of airway epithelial cells.
PMID- 28412396
TI - Systems approach to uncover signaling networks in primary immunodeficiency
diseases.
PMID- 28412397
TI - Caveat on the Boltzmann distribution function use in biology.
AB - Sigmoid semilogarithmic functions with shape of Boltzmann equations, have become
extremely popular to describe diverse biological situations. Part of the
popularity is due to the easy availability of software which fits Boltzmann
functions to data, without much knowledge of the fitting procedure or the
statistical properties of the parameters derived from the procedure. The purpose
of this paper is to explore the plasticity of the Boltzmann function to fit data,
some aspects of the optimization procedure to fit the function to data and how to
use this plastic function to differentiate the effect of treatment on data and to
attest the statistical significance of treatment effect on the data.
PMID- 28412398
TI - Recent Update on Nanoemulgel as Topical Drug Delivery System.
AB - Being an emerging transdermal delivery tool, nanoemulgel, has proved to show
surprising upshots for the lipophilic drugs over other formulations. This
lipophilic nature of majority of the newer drugs developed in this modern era
resulting in poor oral bioavailability, erratic absorption, and pharmacokinetic
variations. Therefore, this novel transdermal delivery system has been proved to
be advantageous over other oral and topical drug delivery to avoid such
disturbances. These nanoemulgels are basically oil-in-water nanoemulsions gelled
with the use of some gelling agent in it. This gel phase in the formulation is
nongreasy, which favors user compliance and stabilizes the formulation through
reduction in surface as well as interfacial tension. Simultaneously, it can be
targeted more specifically to the site of action and can avoid first-pass
metabolism and relieve the user from gastric/systemic incompatibilities. This
brief review is focused on nanoemulgel as a better topical drug delivery system
including its components screening, formulation method, and recent
pharmacokinetic and pharmacodynamic advancement in research studies carried out
by the scientists all over the world. Therefore, at the end of this survey it
could be inferred that nanoemulgel can be a better and effective drug delivery
tool for the topical system.
PMID- 28412399
TI - Quantitative Component Analysis of Solid Mixtures by Analyzing Time Domain 1H and
19F T1 Saturation Recovery Curves (qSRC).
AB - Prevalent polymorphism and complicated phase behavior of active pharmaceutical
ingredients (APIs) often result in remarkable differences in the respective
biochemical and physical API properties. Consequently, API form characterization
and quantification play a central role in the pharmaceutical industry from early
drug development to manufacturing. Here we present a novel and proficient
quantification protocol for solid mixtures (qSRC) based on the measurement and
mathematical fitting of T1 nuclear magnetic resonance (NMR) saturation recovery
curves collected on a bench top time-domain NMR instrument. The saturation
recovery curves of the relevant pure components are used as fingerprints.
Employing a bench top NMR instrument possesses clear benefits. These instruments
exhibit a small footprint, do not present any special requirements on lab space,
and required sample handling is simple and fast. The qSRC analysis can easily be
conducted in a conventional laboratory setting as well as in an industrial
production environment, making it a versatile tool with the potential for
widespread application. The accuracy and efficiency of the qSRC method is
illustrated using 1H and 19F T1 data of selected pharmaceutical model compounds,
as well as utilizing 1H T1 data of an actual binary API anhydrous polymorph
system of a Merck & Co., Inc. compound formerly developed as a hepatitis C virus
drug.
PMID- 28412400
TI - Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following
Losartan Administration Using Static and Physiologically Based Pharmacokinetic
Models.
AB - The aim of this study was to evaluate a strategy based on static and dynamic
physiologically based pharmacokinetic (PBPK) modeling for the prediction of
metabolite and parent drug area under the time-concentration curve ratio
(AUCm/AUCp) and their PK profiles in humans using in vitro data when active
transport processes are involved in disposition. The strategy was applied to
losartan and its pharmacologically active metabolite carboxylosartan as test
compounds. Hepatobiliary transport including transport-mediated uptake,
canilicular and basolateral efflux, and metabolic clearance estimates were
obtained from in vitro studies using human liver microsomes and sandwich-cultured
hepatocytes. Human renal clearance of carboxylosartan was estimated from dog
renal clearance using allometric scaling approach. All clearance mechanisms were
mechanistically incorporated in a static model to predict the relative exposure
of carboxylosartan versus losartan (AUCm/AUCp). The predicted AUCm/AUCp were
consistent with the observed data following intravenous and oral administration
of losartan. Moreover, the in vitro parameters were used as initial parameters in
PBPK permeability-limited disposition models to predict the concentration-time
profiles for both parent and its active metabolite after oral administration of
losartan. The PBPK model was able to recover the plasma profiles of both losartan
and carboxylosartan, further substantiating the validity of this approach.
PMID- 28412401
TI - Proteasome Inhibitor-Loaded Micelles Enhance Antitumor Activity Through
Macrophage Reprogramming by NF-kappaB Inhibition.
AB - Macrophage reprogramming toward a tumor-attacking phenotype is a promising
treatment strategy, yet such strategies are scarce and it is not clear how to
combine them with cytotoxic therapies that are often used to treat solid tumors.
Here, we evaluate whether a micelle-encapsulated proteasome inhibitor, that is,
the peptide aldehyde drug MG132, which is cytotoxic to cancer cells, can
reprogram macrophages to attack the tumor. Through in vitro studies, we
demonstrated that the proteasome inhibition reduces nuclear factor kappa-light
chain-enhancer of activated B cells (NF-kappaB) signaling-a known promoter of
tumor-supporting macrophages and chemoresistance-in both cancer cells and
macrophages. In in vivo studies, we showed that, although free MG132 did not
affect the macrophage phenotype in tumors even at its maximum tolerated dose, the
micellar formulation of MG132 safely achieved simultaneous cancer cell killing
and macrophage reprogramming, thereby enhancing the antitumor efficacy in a
syngeneic, orthotopic breast cancer model.
PMID- 28412402
TI - Flavonoid composition of orange peel extract ameliorates alcohol-induced tight
junction dysfunction in Caco-2 monolayer.
AB - Dry citrus peels, also known as "chenpi", have been traditionally used to treat
and relieve intestinal inflammation. Recently we have reported that orange peel
extracts (OPE) which contain relatively greater polymethoxylated flavone (PMF)
content exhibit superior antioxidant and anti-inflammatory activities in vitro.
Moreover, these bioactivities were notably greater than an equivalent flavonoid
mixture (FM). The present study compares the effects of different OPE sources
with distinct PMF composition on tight junction (TJ) dysfunction induced by
ethanol. The OPE obtained from Xinhui, China, contained a 20-fold higher PMF
content than extracts derived from the orange peels sourced from Guangxi. Xinhui
OPE treatment of ethanol treated Caco-2 cells corresponded to lower (P < 0.05)
lactate dehydrogenase (LDH) leakage and higher (P < 0.05) glutathione reductase
activity. Both OPE and the FM prevented ethanol-induced increases in Caco-2 cell
paracellular permeability and the dislocation of TJ proteins, including claudin
4, occludin, and zonulin occludin-1 (ZO-1), respectively. Xinhui-OPE increased
the expression of claudin 4 and occludin protein, but not mRNA, whereas, Guangxi
OPE and Xinhui-FM had no effect on TJ protein expression. In conclusion, OPE
derived from sources that contain higher concentrations of PMF are more effective
at preventing intestinal barrier dysfunction of TJ proteins induced by ethanol.
PMID- 28412403
TI - A further development of the QNAR model to predict the cellular uptake of
nanoparticles by pancreatic cancer cells.
AB - Nanotechnology has led to the development of new nanomaterials with unique
properties and a wide variety of applications. In the present study, we focused
on the cellular uptake of a group of nanoparticles with a single metal core by
pancreatic cancer cells, which has been studied by Yap et al. (Rsc Advances,
2012, 2 (2):8489-8496) using classification models. In this work, the development
of a further Quantitative Nanostructure-Activity Relationship (QNAR) model was
performed by linear multiple linear regression (MLR) and nonlinear artificial
neural network (ANN) techniques to accurately predict the cellular uptake values
of these compounds by dividing them into three groups. Judging from the attained
statistical results, our derived QNAR models have an acceptable overall accuracy
and robustness, as well as good predictivity on the external data sets. Moreover,
the results of this study provide some insights on how engineered nanomaterial
features influence cellular responses and thereby outline possible approaches for
developing and applying predictive computational models for biological responses
caused by exposure to nanomaterials.
PMID- 28412404
TI - Development of human biotransformation QSARs and application for PBT assessment
refinement.
AB - Toxicokinetics heavily influence chemical toxicity as the result of Absorption,
Distribution, Metabolism (Biotransformation) and Elimination (ADME) processes.
Biotransformation (metabolism) reactions can lead to detoxification or, in some
cases, bioactivation of parent compounds to more toxic chemicals. Moreover,
biotransformation has been recognized as a key process determining chemical half
life in an organism and is thus a key determinant for bioaccumulation assessment
for many chemicals. This study addresses the development of QSAR models for the
prediction of in vivo whole body human biotransformation (metabolism) half-lives
measured or empirically-derived for over 1000 chemicals, mainly represented by
pharmaceuticals. Models presented in this study meet regulatory standards for
fitting, validation and applicability domain. These QSARs were used, in
combination with literature models for the prediction of biotransformation half
lives in fish, to refine the screening of the potential PBT behaviour of over
1300 Pharmaceuticals and Personal Care Products (PPCPs). The refinement of the
PBT screening allowed, among others, for the identification of PPCPs, which were
predicted as PBTs on the basis of their chemical structure, but may be easily
biotransformed. These compounds are of lower concern in comparison to potential
PBTs characterized by large predicted biotransformation half-lives.
PMID- 28412405
TI - Consumption and exposure assessment to cosmetic products for children under 2
years old.
AB - Today, the use of personal care products is an integral part of daily life.
Little information about children's consumption and exposure to cosmetic products
is available. The aim of the study was to assess the consumption and the exposure
of French babies aged 0-23 months old to seven common baby care products:
shampoo, shower gel, cleansing water, cleansing milk, moisturizing cream, bottom
cream and wipes. Consumption and exposure were assessed using small age intervals
in order to identify any differences. Exposure was calculated using a
probabilistic method. These original data will be useful for safety assessors and
safety agencies in order to protect consumers.
PMID- 28412406
TI - Chemical toxicity prediction for major classes of industrial chemicals: Is it
possible to develop universal models covering cosmetics, drugs, and pesticides?
AB - Computational models have earned broad acceptance for assessing chemical toxicity
during early stages of drug discovery or environmental safety assessment. The
majority of publicly available QSAR toxicity models have been developed for
datasets including mostly drugs or drug-like compounds. We have evaluated and
compared chemical spaces occupied by cosmetics, drugs, and pesticides, and
explored whether current computational models of toxicity endpoints can be
universally applied to all these chemicals. Our analysis of the chemical space
overlap and applicability domain (AD) of models built previously for twenty
different toxicity endpoints showed that most of these models afforded high
coverage (>90%) for all three classes of compounds analyzed herein. Only T.
pyriformis models demonstrated lower coverage for drugs and pesticides (38% and
54%, respectively). These results show that, for the most part, historical QSAR
models built with data available for different toxicity endpoints can be used for
toxicity assessment of novel chemicals irrespective of the intended commercial
use; however, the AD restriction is necessary to assure the expected prediction
accuracy. Local models may need to be developed to capture chemicals that appear
as outliers with respect to global models.
PMID- 28412407
TI - Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella
pneumoniae strains producing carbapenemases in an Italian teaching hospital from
January 2015 to September 2016.
AB - OBJECTIVES: We described Klebsiella pneumoniae producing carbapenemase (CPKP)
spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. METHODS: The
first positive surveillance rectal swab (SRS) or clinical sample (CS) collected
in the medical department (MD), surgical department (SD) and intensive care
department (ICD) were included in the study. A validated in-house Real-Time PCR
method was used to detect carbapenemases; multilocus sequence typing (MLST) was
used for further characterization of the strains. RESULTS: 21535 patients were
included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from
clinical samples (CS) were collected. The percentage of CPKP detected in SRS with
respect to CS increased in the medical MD from 2015 to 2016 (p=0.01) and in ICD
from 2012 to 2015 (p=0.0001), while it decreased in SD from 2014 to 2016
(p=0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more
frequently identified in CS than in SRS in MD. Twelve strains harboured more than
one carbapenemase gene. Many other species harbouring a carbapenemase gene were
collected. CONCLUSIONS: MDs need more inclusive surveillance criteria. The late
detection of positive SRS underlined the risk of colonization during
hospitalization.
PMID- 28412408
TI - Breast abscess due to Bacillus Calmette-Guerin.
PMID- 28412409
TI - Development of monoclonal antibodies against Sj29 and its possible application
for schistosomiasis diagnosis.
AB - OBJECTIVE: Timely Schistosoma japonicum detection improves outcomes in
schistosomiasis. Here, we established a double antibody sandwich ELISA to detect
Schistosoma japonicum. METHODS: Sj29 polyclonal and monoclonal antibodies were
developed and identified. A Sj29 double antibody sandwich ELISA was evaluated.
RESULTS: Assay sensitivity for detecting Schistosoma japonicum circulating
antigen Sj29 was 76.7% (23/30), 54.5% (18/33) and 50.0% (18/36) in patients with
acute, chronic and advanced schistosomiasis. No false positives or cross
reactivity was observed in healthy controls or patients with clonorchiasis,
paragonimiasis, or ancylostomiasis, respectively. By contrast, false positives
(5.7%) and cross-reactivity (6.5%-10%) were detected using an AWA-ELISA. The
circulating antigen positive rates decreased significantly faster than that of
the antibody detection after 6 months treatment (22.2%, 4/18 and 88.9%, 16/18).
Chi-Square Tests revealed that Sj29 sandwich ELISA had lower sensitivity than AWA
indirect ELISA in the detection of S. japonicum infected patients (p<0.05).
Although our assay detection specificity in patients infected with other
parasites or healthy controls appeared higher, the difference between the assays
was insignificant. However, our assay showed significantly better results in
monitoring praziquantel therapeutic effects (p=0.001), with antigen-positive
rates decreasing significantly faster than antibody detection rates after 6
months of treatment (22.2%, 4/18 versus 88.9%, 16/18). CONCLUSIONS: Sj29 double
antibody sandwich ELISA was established. The specificity of this method for
detecting healthy sera was 100%. Meanwhile, Sj29 sandwich ELISA may have a
potential diagnostic capability to distinguish current from past infections and
assess drug treatment responses.
PMID- 28412410
TI - Probable pulmonary Blastomyomycocis in an immunocompetent person.
AB - The current case report presents a 29-year old man who worked as a hotel guard in
a city in China. The patient had fever and dry cough before and after
hospitalization. Chest X-ray and CT revealed nodular and patchy lesions in both
lower lungs. There were no abnormal findings in the examination of sputum and
bronchoalveoular lavage fluid (BALF). He was diagnosed with pulmonary
blastomycosis by histological examination of lung biopsy and treated with
fluconazole. Follow-up chest CT examination demonstrated that the patient was
recovered through appropriate antifungal treatment.
PMID- 28412412
TI - Autophagy regulatory molecule, TMEM74, interacts with BIK and inhibits BIK
induced apoptosis.
AB - TMEM74 (Transmembrane protein 74), a lysosome transmembrane protein, induces cell
autophagy. Knockdown of TMEM74 abolished EBSS-induced autophagy. BIK, belonging
to BOP (BH3-only protein) protein family, has been reported to induce cell
apoptosis. Autophagy and apoptosis, as different pathways regulated by extra- or
intra-cellular signals precisely, both play a crucial role in processes of intra
cellular substrates degradation, energy metabolism and cell survival. However,
the relationship between autophagy and apoptosis still remains elusive. To
elucidate the putative new relationship and further identify the function of
TMEM74, we performed the study mainly using co-immunoprecipitation,
immunoblotting, fluorescent location and basic cell biologic experimental
techniques. In the present study, for the first time, it is demonstrated that
autophagy-related protein TMEM74 co-localizes with apoptosis-related protein BIK
in subcellular organelles. The data indicated that TMEM74 associates with BIK via
TM domains of TMEM74 and BH3 domain of BIK. Further investigations revealed that
TMEM74 inhibits BIK-induced apoptosis by interacting with BIK, as evidenced by
the results that autophagosome formation inhibitor could not block the inhibition
effect completely. On the contrary, knockdown of TMEM74 and the TM domain
deficient mutant led to deprivation of the function. Overall, the results
revealed the autophagy modulator TMEM74 interrelates with apoptosis inducer BIK
and inhibits its function, which provides a novel crosstalk point between
autophagy and apoptosis to enlarge our understanding of the programmed cell
death.
PMID- 28412411
TI - Mirtazapine and ketanserin alter preference for gambling-like schedules of
reinforcement in rats.
AB - Drug and behavioral addictions have overlapping features, e.g., both manifest
preference for larger, albeit costlier, reinforcement options in cost/benefit
decision-making tasks. Our prior work revealed that the mixed-function
serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by
abused drugs. To extend this work to behavioral addictions, here we determined if
mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound,
can alter decision-making in rats that is independent of drug (or food)-motivated
reward. Accordingly, we developed a novel variable-ratio task in rats wherein
intracranial self-stimulation was used as the positive reinforcer. Using lever
pressing for various levels of brain stimulation, the operant task provided
choices between a small brain stimulation current delivered on a fixed-ratio
schedule (i.e., a predictable reward) and a large brain stimulation delivered
following an unpredictable number of responses (i.e., a variable-ratio schedule).
This task allowed for demonstration of individualized preference and detection of
shifts in motivational influences during a pharmacological treatment. Once
baseline preference was established, we determined that pretreatment with
mirtazapine or ketanserin significantly decreased preference for the large
reinforcer presented after gambling-like schedules of reinforcement. When the
rats were tested the next day without drug, preference for the unpredictable
large reinforcer option was restored. These data demonstrate that mirtazapine and
ketanserin can reduce preference for larger, costlier reinforcement options, and
illustrate the potential for these drugs to alter behavior.
PMID- 28412413
TI - Activation of muscarinic receptors prevents TNF-alpha-mediated intestinal
epithelial barrier disruption through p38 MAPK.
AB - Intestinal epithelial cells form a tight barrier to act as selective physical
barriers, repelling hostile substances. Tumor necrosis factor-alpha (TNF-alpha)
is a well characterized pro-inflammatory cytokine which can compromise intestinal
barrier function and the suppression of TNF-alpha function is important for
treatment of inflammatory bowel disease (IBD). In this study, we investigated the
contribution of G-protein-coupled receptor (GPCR)-induced signalling pathways to
the maintenance of epithelial barrier function. We first demonstrated the
existence of functional muscarinic M3 and histamine H1 receptors in colonic
epithelial cell HT-29/B6. As we previously reported, muscarinic M3 receptor
prevented TNF-alpha-induced barrier disruption through acceleration of TNF
receptor (TNFR) shedding which is carried out by TNF-alpha converting enzyme
(TACE). M3 receptor-mediated suppression of TNF-alpha function depends on
Galphaq/11 protein, however, histamine H1 receptor could not ameliorate TNF-alpha
function, while which could induce Galphaq/11 dependent intracellular Ca2+
mobilization. We found that p38 MAPK was predominantly phosphorylated by M3
receptor through Galphaq/11 protein, whereas H1 receptor barely upregulated the
phosphorylation. Inhibition of p38 MAPK abolished M3 receptor-mediated TNFR
shedding and suppression of TNF-alpha-induced NF-kappaB signalling. The p38 MAPK
was also involved in TACE- mediated EGFR transactivation followed by ERK1/2
phosphorylation. These results indicate that not H1 but M3 receptor-induced
activation of p38 MAPK might contribute to the maintenance of epithelial barrier
function through down-regulation of TNF-alpha signalling and activation of EGFR.
PMID- 28412415
TI - Stress Echocardiography, Carotid Arteries, and More: Its Versatility for Our
Imaging Times.
PMID- 28412416
TI - Impaired Right Heart and Pulmonary Vascular Function in HFpEF: Time for More Risk
Markers?
PMID- 28412414
TI - Endothelin-1 promotes hypertrophic remodelling of cardiac myocytes by activating
sustained signalling and transcription downstream of endothelin type A receptors.
AB - G-protein coupled receptor (GPCR) mediated activation of the MAPK signalling
cascade is a key pathway in the induction of hypertrophic remodelling of the
heart - a response to pathological cues including hypertension and myocardial
infarction. While levels of pro-hypertrophic hormone agonists of GPCRs increase
during periods of greater workload to enhance cardiac output, hypertrophy does
not necessarily result. Here we investigated the relationship between the
duration of exposure to the pro-hypertrophic GPCR agonist endothelin-1 (ET-1) and
the induction of hypertrophic remodelling in neonatal rat ventricular myocytes
(NRVM) and in the adult rat heart in vivo. Notably, a 15min pulse of ET-1 was
sufficient to induce markers of hypertrophy that were present when measured at
24h in vivo and 48h in vitro. The persistence of ET-1 action was insensitive to
ET type A receptor (ETA receptor) antagonism with BQ123. The extended effects of
ET-1 were dependent upon sustained MAPK signalling and involved persistent
transcription. Inhibitors of endocytosis however conferred sensitivity upon the
hypertrophic response to BQ123, suggesting that endocytosis of ETA receptors
following ligand binding preserves their active state by protection against
antagonist. Contrastingly, alpha1 adrenergic-induced hypertrophic responses
required the continued presence of agonist and were sensitive to antagonist.
These studies shed new light on strategies to pharmacologically intervene in the
action of different pro-hypertrophic mediators.
PMID- 28412417
TI - Coronary Artery Disease Testing: Past, Present, and Future.
PMID- 28412418
TI - Pacemaker Implantation After TAVR.
PMID- 28412419
TI - Image Integration to Guide Wireless Endocardial LV Electrode Implantation for
CRT.
PMID- 28412420
TI - Stress Perfusion CMR in Patients With Known and Suspected CAD: Prognostic Value
and Optimal Ischemic Threshold for Revascularization.
AB - OBJECTIVES: This study sought to determine the ischemia threshold and additional
prognostic factors that identify patients for safe deferral from
revascularizations in a large cohort of all-comer patients with known or
suspected coronary artery disease (CAD). BACKGROUND: Stress-perfusion cardiac
magnetic resonance (CMR) is increasingly used in daily practice for ischemia
detection. However, there is insufficient evidence about the ischemia burden that
identifies patients who benefit from revascularization versus those with a good
prognosis who receive drugs only. METHODS: All patients with known or suspected
CAD referred to stress-perfusion CMR for myocardial ischemia assessment were
prospectively enrolled. The CMR examination included standard functional
adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG,
Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence
of ischemia and ischemia burden (number of ischemic segments on a 16-segment
model), and of scar and scar burden (number and transmurality of scar segments in
a 17-segment model) were assessed. The primary endpoint was a composite of
cardiac death, nonfatal myocardial infarction (MI), and late coronary
revascularization (>90 days post-CMR); the secondary endpoint was a composite of
cardiac death and nonfatal MI. RESULTS: During a follow-up of 2.5 +/- 1.0 years,
86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and
secondary endpoints, respectively. On Kaplan-Meier curves for the primary and
secondary endpoints, patients without ischemia had excellent outcomes that did
not differ from patients with <1.5 ischemic segments. In multivariate Cox
regression analyses of the entire population and of the subgroups, ischemia
burden (threshold: >=1.5 ischemic segments) was consistently the strongest
predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42
to 8.72 (p < 0.001), whereas age (>=67 years), left ventricular ejection fraction
(<=40%), and scar burden (LGE score >=0.03) contributed significantly, but to a
lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to
1.76, respectively. CONCLUSIONS: In a large all-comer patient cohort with known
and suspected CAD, an ischemia burden of >=1.5 ischemic segments on stress
perfusion CMR was the strongest predictor of the primary and secondary endpoints.
Patients with zero or 1 ischemic segment can be safely deferred from
revascularizations.
PMID- 28412421
TI - Change in Carotid Plaque Components: A 4-Year Follow-Up Study With Serial MR
Imaging.
AB - OBJECTIVES: The goal of this study was to determine how carotid plaque components
(e.g., intraplaque hemorrhage [IPH], calcification, lipid core) change over time
and which cardiovascular risk factors are associated with the development of each
component. BACKGROUND: Carotid atherosclerotic plaque components are important
markers of plaque vulnerability. How these components change and which factors
lead to the development and changes in the components remain unclear. METHODS: A
total of 198 participants (mean age 67.5 +/- 10.6 years) from the population
based Rotterdam Study, all with carotid wall thickening on ultrasound, underwent
2 magnetic resonance imaging scans for carotid plaque characterization (mean
interscan interval 4.1 +/- 0.2 years). Presence of IPH, calcification, and lipid
rich necrotic core was assessed on both sides on the baseline and follow-up
scans. The association between cardiovascular risk factors and incident carotid
plaque components was assessed. RESULTS: In the 396 arteries, all plaque
components significantly changed over time. Incidence of IPH, calcification, and
lipid core was, respectively, 18.5%, 59.2%, and 39.6%. The factor most strongly
associated with the incidence of IPH was use of antihypertensive drugs
(multivariate adjusted odds ratio [OR]: 3.87; 95% confidence interval [CI]: 1.90
to 7.90) and severe hypertension (multivariate adjusted OR: 4.70; 95% CI: 1.50 to
14.80). The incidence of calcification was associated with hypertension (OR:
2.20; 95% CI: 1.07 to 4.40). Higher cholesterol levels were associated with
incidence of lipid cores (multivariate adjusted OR per unit increase in
cholesterol: 1.40; 95% CI: 1.10 to 1.70). CONCLUSIONS: In these community
dwelling subjects, characteristics of plaque composition changed dramatically
within a few years, and cardiovascular risk factors played a major role in these
changes. Hypertension and its treatment and serum cholesterol levels were the
main risk factors for the development of atherosclerotic plaque components over
time.
PMID- 28412422
TI - Risk Factors for Development of Carotid Plaque Components.
PMID- 28412424
TI - Toward Noninvasive Assessment of CVP Variations Using Real-Time and Quantitative
Liver Stiffness Estimation.
PMID- 28412423
TI - RV Contractile Function and its Coupling to Pulmonary Circulation in Heart
Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes
and Outcomes.
AB - OBJECTIVES: This study sought to investigate how right ventricular (RV)
contractile function and its coupling with pulmonary circulation (PC) stratify
clinical phenotypes and outcome in heart failure preserved ejection fraction
(HFpEF) patients. BACKGROUND: Pulmonary hypertension and RV dysfunction are key
hemodynamic abnormalities in HFpEF. METHODS: Three hundred eighty seven HFpEF
patients (mean age 64 +/- 12 years, 59% females, left ventricular ejection
fraction 59 +/- 7%) underwent RV and pulmonary hemodynamic evaluation by
echocardiography (entire population) and right heart catheterization (219
patients). Patients were investigated by tricuspid annular plane systolic
excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and
stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3:
>0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to
PC coupling based on the correlation with invasively evaluated RV systolic
elastance/arterial elastance (r = 0.35; p < 0.0001). RESULTS: Groups had similar
prevalence of comorbidities except for a higher prevalence of atrial fibrillation
and kidney dysfunction in tertile 1. Progressively increasing levels of
natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal
exercise aerobic capacity and ventilatory inefficiency were observed from the
highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery
compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed
along the worse portion of the curve at lower pulmonary artery compliance and
higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged
as an independent predictor of worse outcomes. CONCLUSIONS: A thorough assessment
of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at
different level of risk. These observations shift the interest toward therapeutic
strategies that may benefit the right heart as primary unmet need in the complex
pathophysiology of the HFpEF syndrome.
PMID- 28412425
TI - Aortic Dilatation in Repaired Tetralogy of Fallot.
PMID- 28412426
TI - Unraveling the RV Ejection Doppler Envelope: Insight Into Pulmonary Artery
Hemodynamics and Disease Severity.
AB - OBJECTIVES: The purpose of this study was to characterize the profiles of right
ventricular outflow tract (RVOT) Doppler flow velocity envelopes in patients with
pulmonary arterial hypertension (PAH) and to establish whether changes in the
RVOT flow profile related to patient outcome. BACKGROUND: The RVOT systolic flow
profile is frequently abnormal, with findings of a mid-systolic flow deceleration
and notching, previously proposed as an indicator of elevated pulmonary vascular
resistance (PVR). METHODS: We reviewed RVOT systolic flow profiles recorded by
pulsed-wave Doppler from 159 consecutive patients with PAH and measured
deceleration time (DT) of mid-systolic deceleration slope (mid-systolic DT) and
the peak velocity of pre- and post-notching flow. Concurrent right-heart
catheterization was available in all (41 of 41) incident patients and in 39 of
118 established patients. Outcomes, defined as time to all-cause mortality or
need for lung transplantation, were assessed during 3 years of follow-up.
RESULTS: Notched envelopes were identified in 150 of 159 patients. The presence
of a notched pattern and a decrease in the mid-systolic DT were associated with
higher PA pressures; higher PVR; and, at a threshold of a mid-systolic DT of <120
ms, worse outcome. Those patients with a shorter DT were further subdivided based
on the post-notch systolic flow velocity. In these patients, a decline in the
post-notch flow velocity to <62% of the pre-notch flow velocity defined a cohort
with a marked reduction in systolic function and the worst outcome. CONCLUSIONS:
In PAH, the notched profile of RVOT Doppler flow velocity envelope appears to
integrate indicators of pulmonary vascular load and RV function and serves as a
marker for adverse outcomes.
PMID- 28412427
TI - CMR-Verified Regression of Cardiac AL Amyloid After Chemotherapy.
PMID- 28412428
TI - Increased Iron Deposition Is Directly Associated With Myocardial Dysfunction in
Patients With Sickle Cell Disease.
PMID- 28412429
TI - Myocardial Inflammation: An Important Pitfall During CMR T1 Mapping for the
Quantification of Diffuse Fibrosis in Heart Failure.
PMID- 28412430
TI - Incremental Prognostic Value of Stress Echocardiography With Carotid Ultrasound
for Suspected CAD.
AB - OBJECTIVES: This study hypothesized that ischemia and atherosclerosis assessment
by ultrasound (US) may provide incremental prognostic information in patients
with new-onset chest pain who do not have coronary artery disease (CAD).
BACKGROUND: The clinical significance of atherosclerosis assessment by carotid US
in patients undergoing stress echocardiography (SE) in such patients is unknown.
METHODS: Consecutive patients with suspected angina but no history of CAD
underwent simultaneous SE and US prospectively to assess myocardial ischemia and
carotid plaque burden (CPB), respectively. Patients were followed up for major
adverse events (MAEs)-all-cause mortality, nonfatal myocardial infarction, and
unplanned coronary revascularization. RESULTS: Of 591 recruited patients, 580
(men, 46%; mean age 59 +/- 11 years) patients were available for follow-up. SE
demonstrated myocardial ischemia in 12%, but prevalence of carotid plaques was
59%. During a mean follow-up of 1,117 +/- 361 days, 40 first MAEs occurred. In
the multivariable regression model, pre-test probability (PTP) of CAD (p =
0.001), abnormal SE (p < 0.0001), and CPB (p < 0.0001) predicted MAEs. MAE rates
per year increased from 0.9% versus 1.97% versus 4.3% versus 9.7% in patients
with no carotid plaque and normal SE versus patients who had plaque and normal SE
versus those with no plaque and abnormal SE versus patients with plaque and
abnormal SE, respectively (p < 0.0001). In hierarchical analysis, plaque burden
provided incremental prognostic value over PTP of CAD and SE; likewise, SE was
incremental to PTP-CAD and CPB (p < 0.0001 for both). CONCLUSIONS: In patients
with suspected stable angina without known CAD, simultaneous SE (for ischemia)
and US (for atherosclerosis) provided incremental prognostic value.
PMID- 28412431
TI - 3D Morphological Changes in LV and RV During LVAD Ramp Studies.
AB - OBJECTIVES: The purpose of this study was to investigate the differential impact
of the 2 most commonly available left ventricular assist device (LVAD) types on
the right ventricle (RV) and left ventricle (LV) using 3-dimensional (3D)
echocardiography-based analysis of ventricular morphology. BACKGROUND: LVADs have
emerged as common therapy for advanced heart failure. Recent data suggest that
the heart responds differently to speed settings in the 2 main devices available
(HeartMate II [HMII], St Jude Medical, Pleasanton, California, and HVAD,
HeartWare International, Framingham, Massachusetts). The authors hypothesized
that 3D echocardiographic assessment of LV and RV volumes and shape would help
describe the differential impact of the 2 LVAD types on the heart. METHODS:
Simultaneous 3D echocardiography, ramp test, and right heart catheterization were
performed in 31 patients with LVADs (19 with HMII and 12 with HVAD). Device speed
was increased stepwise (8,000 to 12,000 for HMII and 2,300 to 3,200 revolutions
per minute for HVAD). 3D echocardiographic full-volume LV and RV datasets were
acquired, and endocardial surfaces were analyzed using custom software to
calculate LV sphericity, conicity (perfect sphere/cone = 1) and RV septal and
free-wall curvature (0 = flat; <0 = concave; >0 = convex). RESULTS: For both
devices, cardiac output increased and wedge pressure decreased with increasing
speed. In HMII, LV volumes progressively decreased (meanDelta = 127 ml) as the LV
became less spherical and more conical, whereas the RV volume initially remained
stable, but subsequently increased at higher speeds (meanDelta = 60 ml). Findings
for the HVAD were similar, but less pronounced (LV:meanDelta = 51 ml,
RV:meanDelta = 22 ml), and the LV remained significantly more spherical even at
high speeds. On average, in HMII patients, the RV septum became more convex
(bulging into the LV) at the highest speeds whereas in HVAD patients, there was
no discernable change in the RV septum. CONCLUSIONS: The heart responds
differently to pump speed changes with the 2 types of LVAD, as reflected by the
volume and shape changes of both the LV and RV. Our study suggests that adding RV
assessment to the clinical echo-ramp study may better optimize LVAD speed.
Further study is needed to determine whether this would have an impact on patient
outcomes.
PMID- 28412432
TI - Prognostic Value and Determinants of CMR-Derived Left Atrial Function Assessed in
STEMI.
PMID- 28412433
TI - Increased Lipid Length, Macrophage Infiltration, and Neovascularization in
Coronary Atheroma From Patients With Chronic Kidney Disease.
PMID- 28412434
TI - A Highly Predictive Risk Model for Pacemaker Implantation After TAVR.
AB - OBJECTIVES: This study sought to develop a robust and definitive risk model for
new permanent pacemaker implantation (PPMI) after SAPIEN 3 (third generation
balloon expandable valve) (Edwards Lifesciences, Irvine, California)
transcatheter aortic valve replacement (third generation balloon expandable valve
TAVR), including calcification in the aortic-valvular complex (AVC). BACKGROUND:
The association between calcium in the AVC and need for PPMI is poorly delineated
after third generation balloon expandable valve TAVR. METHODS: At Cedars-Sinai
Heart Institute in Los Angeles, California, a total of 240 patients with severe
aortic stenosis underwent third generation balloon expandable valve TAVR and had
contrast computed tomography. AVC was characterized precisely by leaflet sector
and region. RESULTS: The total new PPMI rate was 14.6%. On multivariate analysis
for predictors of PPMI, pre-procedure third generation balloon expandable valve
TAVR, right bundle branch block (RBBB), shorter membranous septum (MS) length,
and noncoronary cusp device-landing zone calcium volume (NCC-DLZ CA) were
included. Predictive probabilities were generated using this logistic regression
model. If 3 pre-procedural risk factors were present, the c-statistic of the
model for PPMI was area under the curve of 0.88, sensitivity of 77.1%, and
specificity of 87.1%; this risk model had high negative predictive value (95.7%).
The addition of the procedural factor of device depth to the model, with the
parameter of difference between implantation depth and MS length, combined with
RBBB and NCC-DLZ CA increased the c-statistic to 0.92, sensitivity to 94.3%,
specificity to 83.8%, and negative predictive value to 98.8% CONCLUSIONS: By
using a precise characterization of distribution of calcification in the AVC in a
single-center, retrospective study, NCC-DLZ CA was found to be an independent
predictor of new PPMI post-third generation balloon expandable valve TAVR. The
findings also reinforce the importance of short MS length, pre-existing RBBB, and
ventricular implantation depth as important synergistic PPMI risk factors. This
risk model will need validation by future prospective multicenter studies.
PMID- 28412435
TI - CMR-Derived Extracellular Volume Fraction as a Marker for Myocardial Fibrosis:
The Importance of Coexisting Myocardial Inflammation.
AB - OBJECTIVES: The aim of the present study was to evaluate whether extracellular
volume fraction (ECV) can reliably inform on the extent of diffuse fibrosis in
the simultaneous presence of myocardial inflammation, which has not been verified
to date. BACKGROUND: Diffuse myocardial fibrosis is associated with unfavorable
outcome in patients with cardiomyopathy, and is of prognostic relevance.
Assessment of ECV bears promise for being a noninvasive surrogate parameter, but
it may be altered by other pathologies. METHODS: In this prospective study, 107
consecutive patients with clinical suspicion of inflammatory cardiomyopathy were
included. All patients underwent left ventricular (LV) endomyocardial biopsy
(EMB) and cardiac magnetic resonance imaging on a 1.5-T scanner. T1 mapping was
obtained with the modified Look-Locker inversion recovery sequence, and ECV was
calculated. RESULTS: Myocardial inflammation was present in 66 patients. Patients
with and without inflammation were of similar age and had comparable LV ejection
fraction (37 +/- 17% vs. 36 +/- 18%; p = 0.9) and symptom duration (median 14
days [interquartile range: 5 to 36 days] vs. median 14 days [interquartile range:
7 to 30 days]; p = 0.73). Although LV collagen volume percentage was comparable
between groups (inflammation 12.3 +/- 17.8% vs. noninflammation 11.4 +/- 7.9%; p
= 0.577), ECV was significantly higher in patients with inflammation (0.37 +/-
0.06%) than in those without inflammation (0.33 +/- 0.08%; p = 0.02).
Importantly, ECV adequately estimated the degree of LV fibrosis percentage only
in patients without inflammation (r = 0.72; p < 0.0001) and not in those with
inflammation (r = 0.24; p = 0.06). CONCLUSIONS: These findings prove the
theoretical concept of ECV as an estimate for diffuse myocardial fibrosis, but
only in the absence of significant myocardial inflammation. Assuming that various
degrees of myocardial inflammation and fibrosis coexist in such a scenario, the
measured ECV will reflect a sum of these different pathologies but will not
inform solely on the extent of diffuse fibrosis.
PMID- 28412437
TI - 3D Echocardiography and Ventricular Unloading With Continuous Flow LVAD:
Potential Advantages to Optimize Patient Outcome.
PMID- 28412436
TI - Noninvasive FFR Derived From Coronary CT Angiography: Management and Outcomes in
the PROMISE Trial.
AB - OBJECTIVES: The purpose of this study was to determine whether noninvasive
fractional flow reserve derived from computed tomography (FFRCT) predicts
coronary revascularization and outcomes and whether its addition improves
efficiency of referral to invasive coronary angiography (ICA) after coronary
computed tomography angiography (CTA). BACKGROUND: FFRCT may improve the
efficiency of an anatomic CTA strategy for stable chest pain. METHODS: This
observational cohort study included patients with stable chest pain in the
PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain)
trial referred to ICA within 90 days after CTA. FFRCT was measured at a blinded
core laboratory, and FFRCT results were unavailable to caregivers. We determined
the agreement of FFRCT (positive if <=0.80) with stenosis on CTA and ICA
(positive if >=50% left main or >=70% other coronary artery), and predictive
value for a composite of coronary revascularization or major adverse cardiac
events (death, myocardial infarction, or unstable angina). We retrospectively
assessed whether adding FFRCT <=0.80 as a gatekeeper could improve efficiency of
referral to ICA, defined as decreased rate of ICA without >=50% stenosis and
increased ICA leading to revascularization. RESULTS: FFRCT was calculated in 67%
(181 of 271) of eligible patients (mean age 62 years; 36% women). FFRCT was
discordant with stenosis in 31% (57 of 181) for CTA and 29% (52 of 181) for ICA.
Most patients undergoing coronary revascularization had an FFRCT of <=0.80 (91%;
80 of 88). An FFRCT of <=0.80 was a significantly better predictor for
revascularization or major adverse cardiac events than severe CTA stenosis (HR:
4.3 [95% confidence interval [CI]: 2.4 to 8.9] vs. 2.9 [95% CI: 1.8 to 5.1]; p =
0.033). Reserving ICA for patients with an FFRCT of <=0.80 could decrease ICA
without >=50% stenosis by 44%, and increase the proportion of ICA leading to
revascularization by 24%. CONCLUSIONS: In this hypothesis-generating study of
patients with stable chest pain referred to ICA from CTA, an FFRCT of <=0.80 was
a better predictor of revascularization or major adverse cardiac events than
severe stenosis on CTA. Adding FFRCT may improve efficiency of referral to ICA
from CTA alone.
PMID- 28412438
TI - Torsional stress promotes trinucleotidic expansion in spermatids.
AB - Trinucleotide repeats are involved in various neurodegenerative diseases and are
highly unstable both in dividing or non-dividing cells. In Huntington disease
(HD), the age of onset of symptoms is inversely correlated to the number of CAG
repeats within exon 1 of the HTT gene. HD shows paternal anticipation as CAG
repeats are increased during spermatogenesis. CAG expansion were indeed found to
be generated during the chromatin remodeling in spermatids where most histones
are evicted and replaced by protamines. This process involves striking change in
DNA topology since free supercoils must be eliminated. Using an in vitro CAG
repeat reporter assay and a highly active nuclear extracts from spermatids, we
demonstrate that free negative supercoils result in CAG TNR expansion at a
stabilized hairpin. We also suggest a possible role for protamines in promoting
localized torsional stress and consequently TNR expansion. The transient increase
in torsional stress during spermiogenesis may therefore provide an ideal context
for the generation of such secondary DNA structures leading to the paternal
anticipation of trinucleotidic diseases.
PMID- 28412439
TI - Musical literacy shifts asymmetries in the ventral visual cortex.
AB - The acquisition of literacy has a profound impact on the functional
specialization and lateralization of the visual cortex. Due to the overall
lateralization of the language network, specialization for printed words develops
in the left occipitotemporal cortex, allegedly inducing a secondary shift of
visual face processing to the right, in literate as compared to illiterate
subjects. Applying the same logic to the acquisition of high-level musical
literacy, we predicted that, in musicians as compared to non-musicians,
occipitotemporal activations should show a leftward shift for music reading, and
an additional rightward push for face perception. To test these predictions,
professional musicians and non-musicians viewed pictures of musical notation,
faces, words, tools and houses in the MRI, and laterality was assessed in the
ventral stream combining ROI and voxel-based approaches. The results supported
both predictions, and allowed to locate the leftward shift to the inferior
temporal gyrus and the rightward shift to the fusiform cortex. Moreover, these
laterality shifts generalized to categories other than music and faces. Finally,
correlation measures across subjects did not support a causal link between the
leftward and rightward shifts. Thus the acquisition of an additional perceptual
expertise extensively modifies the laterality pattern in the visual system.
PMID- 28412440
TI - Transient networks of spatio-temporal connectivity map communication pathways in
brain functional systems.
AB - The study of brain dynamics enables us to characterize the time-varying
functional connectivity among distinct neural groups. However, current methods
suffer from the absence of structural connectivity information. We propose to
integrate infra-slow neural oscillations and anatomical-connectivity maps, as
derived from functional and diffusion MRI, in a multilayer-graph framework that
captures transient networks of spatio-temporal connectivity. These networks group
anatomically wired and temporary synchronized brain regions and encode the
propagation of functional activity on the structural connectome. In a group of 71
healthy subjects, we find that these transient networks demonstrate power-law
spatial and temporal size, globally organize into well-known functional systems
and describe wave-like trajectories of activation across anatomically connected
regions. Within the transient networks, activity propagates through polysynaptic
paths that include selective ensembles of structural connections and differ from
the structural shortest paths. In the light of the communication-through
coherence principle, the identified spatio-temporal networks could encode
communication channels' selection and neural assemblies, which deserves further
attention. This work contributes to the understanding of brain structure-function
relationships by considering the time-varying nature of resting-state
interactions on the axonal scaffold, and it offers a convenient framework to
study large-scale communication mechanisms and functional dynamics.
PMID- 28412441
TI - Noise-robust cortical tracking of attended speech in real-world acoustic scenes.
AB - Selectively attending to one speaker in a multi-speaker scenario is thought to
synchronize low-frequency cortical activity to the attended speech signal. In
recent studies, reconstruction of speech from single-trial electroencephalogram
(EEG) data has been used to decode which talker a listener is attending to in a
two-talker situation. It is currently unclear how this generalizes to more
complex sound environments. Behaviorally, speech perception is robust to the
acoustic distortions that listeners typically encounter in everyday life, but it
is unknown whether this is mirrored by a noise-robust neural tracking of attended
speech. Here we used advanced acoustic simulations to recreate real-world
acoustic scenes in the laboratory. In virtual acoustic realities with varying
amounts of reverberation and number of interfering talkers, listeners selectively
attended to the speech stream of a particular talker. Across the different
listening environments, we found that the attended talker could be accurately
decoded from single-trial EEG data irrespective of the different distortions in
the acoustic input. For highly reverberant environments, speech envelopes
reconstructed from neural responses to the distorted stimuli resembled the
original clean signal more than the distorted input. With reverberant speech, we
observed a late cortical response to the attended speech stream that encoded
temporal modulations in the speech signal without its reverberant distortion.
Single-trial attention decoding accuracies based on 40-50s long blocks of data
from 64 scalp electrodes were equally high (80-90% correct) in all considered
listening environments and remained statistically significant using down to 10
scalp electrodes and short (<30-s) unaveraged EEG segments. In contrast to the
robust decoding of the attended talker we found that decoding of the unattended
talker deteriorated with the acoustic distortions. These results suggest that
cortical activity tracks an attended speech signal in a way that is invariant to
acoustic distortions encountered in real-life sound environments. Noise-robust
attention decoding additionally suggests a potential utility of stimulus
reconstruction techniques in attention-controlled brain-computer interfaces.
PMID- 28412442
TI - Human brain mapping: A systematic comparison of parcellation methods for the
human cerebral cortex.
AB - The macro-connectome elucidates the pathways through which brain regions are
structurally connected or functionally coupled to perform a specific cognitive
task. It embodies the notion of representing and understanding all connections
within the brain as a network, while the subdivision of the brain into
interacting functional units is inherent in its architecture. As a result, the
definition of network nodes is one of the most critical steps in connectivity
network analysis. Although brain atlases obtained from cytoarchitecture or
anatomy have long been used for this task, connectivity-driven methods have
arisen only recently, aiming to delineate more homogeneous and functionally
coherent regions. This study provides a systematic comparison between anatomical,
connectivity-driven and random parcellation methods proposed in the thriving
field of brain parcellation. Using resting-state functional MRI data from the
Human Connectome Project and a plethora of quantitative evaluation techniques
investigated in the literature, we evaluate 10 subject-level and 24 groupwise
parcellation methods at different resolutions. We assess the accuracy of
parcellations from four different aspects: (1) reproducibility across different
acquisitions and groups, (2) fidelity to the underlying connectivity data, (3)
agreement with fMRI task activation, myelin maps, and cytoarchitectural areas,
and (4) network analysis. This extensive evaluation of different parcellations
generated at the subject and group level highlights the strengths and
shortcomings of the various methods and aims to provide a guideline for the
choice of parcellation technique and resolution according to the task at hand.
The results obtained in this study suggest that there is no optimal method able
to address all the challenges faced in this endeavour simultaneously.
PMID- 28412443
TI - Separating blood and water: Perfusion and free water elimination from diffusion
MRI in the human brain.
AB - The assessment of the free water fraction in the brain provides important
information about extracellular processes such as atrophy and neuroinflammation
in various clinical conditions as well as in normal development and aging. Free
water estimates from diffusion MRI are assumed to account for freely diffusing
water molecules in the extracellular space, but may be biased by other pools of
molecules in rapid random motion, such as the intravoxel incoherent motion (IVIM)
of blood, where water molecules perfuse in the randomly oriented capillary
network. The goal of this work was to separate the signal contribution of the
perfusing blood from that of free-water and of other brain diffusivities. The
influence of the vascular compartment on the estimation of the free water
fraction and other diffusivities was investigated by simulating perfusion in
diffusion MRI data. The perfusion effect in the simulations was significant,
especially for the estimation of the free water fraction, and was maintained as
long as low b-value data were included in the analysis. Two approaches to reduce
the perfusion effect were explored in this study: (i) increasing the minimal b
value used in the fitting, and (ii) using a three-compartment model that
explicitly accounts for water molecules in the capillary blood. Estimation of the
model parameters while excluding low b-values reduced the perfusion effect but
was highly sensitive to noise. The three-compartment model fit was more stable
and additionally, provided an estimation of the volume fraction of the capillary
blood compartment. The three-compartment model thus disentangles the effects of
free water diffusion and perfusion, which is of major clinical importance since
changes in these components in the brain may indicate different pathologies,
i.e., those originating from the extracellular space, such as neuroinflammation
and atrophy, and those related to the vascular space, such as vasodilation,
vasoconstriction and capillary density. Diffusion MRI data acquired from a
healthy volunteer, using multiple b-shells, demonstrated an expected non-zero
contribution from the blood fraction, and indicated that not accounting for the
perfusion effect may explain the overestimation of the free water fraction
evinced in previous studies. Finally, the applicability of the method was
demonstrated with a dataset acquired using a clinically feasible protocol with
shorter acquisition time and fewer b-shells.
PMID- 28412444
TI - Hypoxia-inducible microRNA-218 inhibits trophoblast invasion by targeting LASP1:
Implications for preeclampsia development.
AB - Preeclampsia (PE) is a major contributor to maternal morbidity and mortality.
However, the molecular mechanisms underlying PE progression are not well
characterized. Here, we investigated the role of miR-218 in PE development. The
expression of miR-218 and its host genes SLIT2 and SLIT3 was up-regulated in
preeclamptic placentae compared to normal placentae. miR-218 expression was
induced by hypoxia and decreased after knockdown of HIF-1alpha in an extravillous
trophoblast cell line (HTR-8/SVneo). Chromatin immunoprecipitation assays showed
direct binding of HIF-1alpha to the promoters of SLIT2 and SLIT3. Bioinformatics
analysis identified LASP1 as a direct target of miR-218. Overexpression of miR
218 repressed the expression of LASP1 at both the mRNA and protein level.
Meanwhile, miR-218 repressed the activity of a luciferase reporter containing the
3'-untranslated region of the LASP1 gene. Furthermore, expression of LASP1
rescued the inhibitory effect of miR-218 on HTR-8/SVneo cell invasion. Together,
these results indicated that miR-218 contributes to PE by targeting LASP1 to
inhibit trophoblast invasion.
PMID- 28412445
TI - Methylphenidate effects in the young brain: friend or foe?
AB - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH)
is a first-line stimulant drug available worldwide for its treatment. Despite the
proven therapeutic efficacy, concerns have been raised regarding the possible
consequences of chronic MPH exposure during childhood and adolescence.
Disturbances in the neurodevelopment at these crucial stages are major concerns
given the unknown future life consequences. This review is focused on the long
term adverse effects of MPH to the brain biochemistry. Reports conducted with
young and/or adolescent animals and studies with humans are reviewed in the
context of long-term consequences after early life-exposure. MPH pharmacokinetics
is also reviewed as there are differences among laboratory animals and humans
that may be relevant to extrapolate the findings. Studies reveal that exposure to
MPH in laboratory animals during young and/or adolescent ages can impact the
brain, but the outcomes are dependent on MPH dose, treatment period, and animal's
age. Importantly, the female sex is largely overlooked in both animal and human
studies. Unfortunately, human reports that evaluate adults following adolescent
or child exposure to MPH are very scarce. In general, human data indicates that
MPH is generally safe, although it can promote several brain changes in early
ages. Even so, there is a lack of long course patient evaluation to clearly
establish whether MPH-induced changes are friendly or foe to the brain and more
human studies are needed to assess the adult brain changes that arise from early
MPH treatment.
PMID- 28412447
TI - Improved release of triamcinolone acetonide from medicated soft contact lenses
loaded with drug nanosuspensions.
AB - Drug nanosuspensions (NSs) show a significant potential to improve loading and
release properties of the poorly water soluble drug triamcinolone acetonide (TA)
from poly(hydroxyethyl methacrylate) (pHEMA) soft contact lenses. In this work,
TA NSs were developed by a controlled precipitation method using a fractional
factorial Plackett-Burmann design. Poloxamer 407 (PL) and polyvinyl alcohol (PVA)
as stabilizing agents were selected. NSs were characterized in terms of their
drug content, particle size and morphology. Results indicate that all studied
factors, except homogenization speed and sonication, have significant influence
on the drug incorporation yield into NSs. Drug nanoparticles showed an
interesting size that may be suitable for their incorporation into topical ocular
drug delivery systems, as hydrogels. pHEMA hydrogels and daily-wear Hilafilcon B
commercial contact lenses (SCLs) were employed to study TA loading capacity and
drug release properties using NSs as loading system. Hydrogels have been
synthesised by copolymerization of 2-hydroxyethyl methacrylate (HEMA) with
methacrylic acid (MA) in accordance with a previous work (Garcia-Millan et al.,
2015). Both synthesised hydrogels and SCLs were characterized in terms of their
mechanical and physical properties and TA loading and release properties.
Selected TA NS was further characterized by studying its physical-chemical
stability during the loading process. Results show that the use of TA NSs as
loading medium significantly increases drug loading capacity and release of soft
contact lenses in comparison with drug saturated solution. Synthesised pHEMA
hydrogels and SCLs lenses have good properties as ophthalmic drug delivery
systems, but SCLs load higher quantities of drug and release TA in shorter time
periods than synthesised pHEMA hydrogel.
PMID- 28412446
TI - Development and characterization of mucoadhesive buccal gels containing lipid
nanoparticles of ibuprofen.
AB - The lipid nanoparticles, namely Nanostructured Lipid Carriers (NLC), as drug
delivery systems have been investigated for several years. One of the delivery
routes for which these carriers can be applied is buccal administration. However,
the liquid dispersions of lipid nanoparticles can be rapidly removed from oral
cavity by saliva. Thus, the development of a system that allows increased
retention time on the mucosa is necessary. For this reason, the development of
mucoadhesive preparations for buccal administration of lipid nanoparticles
becomes important. Hydrogels prepared with mucoadhesive polymers (Carbopol(r) 980
and polycarbophil) constitute a promising option. The aim of this work was to
develop mucoadhesive buccal hydrogels with NLC, using ibuprofen as a model drug.
The obtained results showed that the developed NLC dispersions presented
particles in the nanometric size range, with low polydispersity index values and
efficient ability for the entrapment of the model drug. Moreover, the
incorporation of NLC in hydrogels of mucoadhesive polymers resulted in
preparations with desirable rheological features as well as texture (firmness and
adhesiveness) and mucoadhesive properties, which could benefit the therapeutic
efficacy, by increasing the residence time and easiness for topical application
in the buccal mucosa. Additionally, the developed preparations exhibited
sustained drug release as intended for these systems.
PMID- 28412448
TI - Self-assembled liposomes of dual paclitaxel-phospholipid prodrug for anticancer
therapy.
AB - In this report, a newly liposomal formulation of paclitaxel (PTX) based on dual
paclitaxel succinate glycerophosphorylcholine (Di-PTX-GPC) prodrug was developed.
The Di-PTX-GPC prodrug was synthesized by conjugating PTX with GPC through
esterification under N,N'-carbonyldiimidazole (CDI) and 1,8
diazabicyclo[5.4.0]undec-7-ene (DBU) catalytic system. Di-PTX-GPC liposomes were
prepared by thin film method and characterized by dynamic light scattering (DLS)
and transmission electron microscope (TEM). The results indicated that the
liposomes have an average diameter of 157.9nm with well-defined spherical
morphology. In vitro drug release studies confirmed that the Di-PTX-GPC liposomes
have controlled release profile of PTX at a weakly acidic environment, which
formulates them suitable for sustained drug delivery. Additionally, in vitro
cellular uptake analysis and cytotoxicity evaluation showed that Di-PTX-GPC
liposomes were internalized successfully into tumor cells to induce the apoptosis
against MCF-7, HeLa and HepG-2 cells. In vivo pharmacokinetics study revealed
that such liposomal formulation of Di-PTX-GPC has longer retention half-life in
bloodstream, which subsequently leads to slight accumulate in tumor sites due to
enhanced permeability and retention (EPR) effect. More importantly, Di-PTX-GPC
liposomes demonstrated good in vivo anticancer activities compared to Taxol with
reduced adverse effects. Conclusively, these results suggest that Di-PTX-GPC
liposomes could be an effective PTX delivery vehicles in clinical cancer
chemotherapy.
PMID- 28412449
TI - Targeted drug delivery system to neural cells utilizes the nicotinic
acetylcholine receptor.
AB - Drug delivery to the brain is still a major challenge in the field of
therapeutics, especially for large and hydrophilic compounds. In order to achieve
drug delivery of therapeutic concentration in the central nervous system, the
problematic blood brain barrier (BBB) must be overcome. This work presents the
formulation of a targeted nanoparticle-based drug delivery system using a
specific neural cell targeting ligand, rabies virus derived peptide (RDP).
Characterization studies revealed that RDP could be conjugated to drug-loaded
PLGA nanoparticles of average diameter 257.10+/-22.39nm and zeta potential of
5.51+/-0.73mV. In vitro studies showed that addition of RDP to nanoparticles
enhanced drug accumulation in a neural cell line specifically as opposed to non
neural cell lines. It was revealed that this drug delivery system is reliant upon
nicotinic acetylcholine receptor (nAChR) function for RDP-facilitated effects,
supporting a cellular uptake mechanism of action. The specific neural cell
targeting capabilities of RDP via the nAChR offers a non-toxic, non-invasive and
promising approach to the delivery of therapeutics to the brain.
PMID- 28412450
TI - PEGylated doxorubicin nanoparticles mediated by HN-1 peptide for targeted
treatment of oral squamous cell carcinoma.
AB - HN-1, a 12-amino acid peptide, has been reported to possess strong capabilities
for targeting and penetrating head and neck squamous cell carcinoma. Here, we
designed a simple but effective nanoparticle system for the delivery of
doxorubicin (DOX) targeting oral squamous cell carcinoma (OSCC) through the
mediation of HN-1. PEGylated DOX (PD) was firstly synthesized by the conjugation
of DOX with bis-amino-terminated poly(ethylene glycol) via succinyl linkage, and
then PD nanoparticles were prepared by a modified nanoprecipitation method. After
that, PD nanoparticles were surface-modified with HN-1 to form HNPD
nanoparticles, which had a uniform spherical shape and a small size about 150nm.
In human OSCC cells (CAL-27 and SCC-25), HNPD nanoparticles exhibited
significantly higher cellular uptakes and cytotoxicities than PD nanoparticles.
Furthermore, HNPD nanoparticles showed a certain degree of functional selectivity
for CAL-27 and SCC-25 cells as compared to human hepatoma HepG2 cells. In SCC-25
tumor-bearing nude mice, HNPD nanoparticles showed remarkably enhanced tumor
targeting and penetrating efficiencies as compared to PD nanoparticles, and
effectively inhibited the tumor growth. In conclusion, our study demonstrated for
the first time that HN-1 could be used for mediating the OSCC-targeted delivery
of nanoparticles.
PMID- 28412451
TI - Laser-treated electrospun fibers loaded with nano-hydroxyapatite for bone tissue
engineering.
AB - Core-shell polycaprolactone/polycaprolactone (PCL/PCL) and
polycaprolactone/polyvinyl acetate (PCL/PVAc) electrospun fibers loaded with
synthesized nanohydroxyapatite (HAn) were lased treated to create microporosity.
The prepared materials were characterized by XRD, FTIR, TEM and SEM. Uniform and
randomly oriented beadless fibrous structures were obtained in all cases. Fibers
diameters were in the 150-300nm range. Needle-like HAn nanoparticles with mean
diameters of 20nm and length of approximately 150nm were mostly encase inside the
fibers. Laser treated materials present micropores with diameters in the range 70
120MUm for PCL-HAn/PCL fibers and in the 50-90MUm range for PCL-HAn/PVAC
material. Only samples containing HAn presented bioactivity after incubation
during 30days in simulated body fluid. All scaffolds presented high viability,
very low mortality, and human osteoblast proliferation. Biocompatibility was
increased by laser treatment due to the surface and porosity modification.
PMID- 28412452
TI - Enhancement of dissolution rate through eutectic mixture and solid solution of
posaconazole and benznidazole.
AB - Benznidazole (BNZ), the only commercialized antichagasic drug, and the antifungal
compound posaconazole (PCZ) have shown synergistic action in the therapy of
Chagas disease, however both active pharmaceutical ingredients (APIs) exhibit low
aqueous solubility potentially limiting their bioavailability and therapeutic
efficacy. In this paper, we report for the first time the formation of a eutectic
mixture as well as an amorphous solid solution of PCZ and BNZ (at the same
characteristic ratio of 80:20wt%), which provided enhanced solubility and
dissolution rate for both APIs. This eutectic system was characterized by DSC and
the melting points obtained were used for the construction of a phase diagram.
The preservation of the characteristic PXRD patterns and the IR spectra of the
parent APIs, and the visualization of a characteristic eutectic lamellar
crystalline microstructure using Confocal Raman Microscopy confirm this system as
a true eutectic mixture. The PXRD result also confirms the amorphous nature of
the prepared solid solution. Theoretical chemical analyses indicate the
predominance of pi-stacking interactions in the amorphous solid solution, whereas
an electrostatic interaction between the APIs is responsible for maintaining the
alternating lamellar crystalline microstructure in the eutectic mixture. Both the
eutectic mixture and the amorphous solid solution happen to have a characteristic
PCZ to BNZ ratio similar to that of their pharmacological doses for treating
Chagas disease, thus providing a unique therapeutic combination dose with
enhanced apparent solubility and dissolution rate.
PMID- 28412453
TI - In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and
common laboratory animals.
AB - Cyanide is a metabolic poison that inhibits cytochrome c oxidase. Its broad
applications in manufacturing and history as an agent of warfare/terror highlight
the limitations in approved cyanide antidotes for mass casualties. Sulfanegen, a
pre-clinical antidote for cyanide poisoning, exploits an endogenous
detoxification pathway and should be amenable to mass-casualty scenarios. Because
human studies are unethical, determination of appropriate animal species as
models in translational studies for FDA approval under the "Animal Rule" are
critical. Here, we compared the specific activities of mercaptopyruvate
sulfurtransferase (MST, required for sulfanegen's activity), across common
laboratory models of cyanide intoxication, and humans. Human MST activities in
erythrocytes (measured as micromole pyruvate/min/106 rbc) were closest to those
of Swiss-Webster mice and NZW rabbits. Similar species were selected for a more
detailed tissue-specific comparison of MST activities. NZW Rabbits were closest
to humans in the liver and kidney mitochondrial fractions, the Swiss-Webster
mouse was closest to humans in the liver cytosolic fraction, while C57BL/6 mouse
was closest in the kidney cytosolic fraction. These data comparing MST activities
in animal models will help justify the use of those specific animals per the
animal rule. Interestingly, statistically significant differences were found in
MST activities of liver mitochondria between human smokers and non-smokers
(p=0.0030).
PMID- 28412454
TI - New insights into the toxicity of mineral fibres: A combined in situ synchrotron
MU-XRD and HR-TEM study of chrysotile, crocidolite, and erionite fibres found in
the tissues of Sprague-Dawley rats.
AB - Along the line of the recent research topic aimed at understanding the in vivo
activity of mineral fibres and their mechanisms of toxicity, this work describes
the morpho-chemical characteristics of the mineral fibres found in the tissues of
Sprague-Dawley rats subjected to intraperitoneal/intrapleural injection of UICC
chrysotile, UICC crocidolite and erionite-Na from Nevada (USA). The fibres are
studied with in situ synchrotron powder diffraction and high resolution
transmission electron microscopy to improve our understanding of the mechanisms
of toxicity of these mineral fibres. In contact with the tissues of the rats,
chrysotile fibres are prone to dissolve, with leaching of Mg and production of a
silica rich relict. On the other hand, crocidolite and erionite-Na fibres are
stable even for very long contact times within the tissues of the rats, showing
just a thin dissolution amorphous halo. These findings support the model of a
lower biopersistence of chrysotile with respect to crocidolite and erionite-Na
but the formation of a silica-rich fibrous residue after the pseudo-amorphization
of chrysotile may justify a higher cytotoxic potential and intense inflammatory
activity of chrysotile in the short term in contact with the lung tissues.
PMID- 28412455
TI - Effects of RF pulse profile and intra-voxel phase dispersion on MR fingerprinting
with balanced SSFP readout.
AB - PURPOSE: To investigate possible errors in T1 and T2 quantification via MR
fingerprinting with balanced steady-state free precession readout in the presence
of intra-voxel phase dispersion and RF pulse profile imperfections, using
computer simulations based on Bloch equations. MATERIALS AND METHODS: A pulse
sequence with TR changing in a Perlin noise pattern and a nearly sinusoidal
pattern of flip angle following an initial 180-degree inversion pulse was
employed. Gaussian distributions of off-resonance frequency were assumed for
intra-voxel phase dispersion effects. Slice profiles of sinc-shaped RF pulses
were computed to investigate flip angle profile influences. Following
identification of the best fit between the acquisition signals and those
established in the dictionary based on known parameters, estimation errors were
reported. In vivo experiments were performed at 3T to examine the results.
RESULTS: Slight intra-voxel phase dispersion with standard deviations from 1 to
3Hz resulted in prominent T2 under-estimations, particularly at large T2 values.
T1 and off-resonance frequencies were relatively unaffected. Slice profile
imperfections led to under-estimations of T1, which became greater as regional
off-resonance frequencies increased, but could be corrected by including slice
profile effects in the dictionary. Results from brain imaging experiments in vivo
agreed with the simulation results qualitatively. CONCLUSION: MR fingerprinting
using balanced SSFP readout in the presence of intra-voxel phase dispersion and
imperfect slice profile leads to inaccuracies in quantitative estimations of the
relaxation times.
PMID- 28412456
TI - Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin
cancer through enhanced repair of damaged DNA-dependent activation of immune
sensitivity.
AB - Numerous plant products have been used to prevent and manage a wide variety of
diseases for centuries. These products are now considered as promising options
for the development of more effective and less toxic alternatives to the systems
of medicine developed primarily in developed countries in the modern era. Grape
seed proanthocyanidins (GSPs) are of great interest due to their anti
carcinogenic effects that have been demonstrated using various tumor models
including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre
clinical mouse model supplementation of a control diet (AIN76A) with GSPs at
concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and
multiplicity of UVB radiation-induced skin tumors. In this review, we summarize
the evidence that this inhibition of UVB-induced skin tumor development by
dietary GSPs is mediated by a multiplicity of coordinated effects including: (i)
Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and
(ii) DNA repair-dependent stimulation of the immune system following the
functional activation of dendritic cells and effector T cells. Dietary GSPs hold
promise for the development of an effective alternative strategy for the
prevention of excessive solar UVB radiation exposure-induced skin diseases
including the risk of non-melanoma skin cancer in humans.
PMID- 28412457
TI - Identification and expression analysis of alternatively spliced new transcript
isoform of Bax gene in mouse.
AB - Bax, a pro-apoptotic member of Bcl-2 family regulates apoptosis through
homodimerization/heterodimerization with Bcl-2. Bax-alpha is the only product of
the Bax gene that has been extensively studied. Bax-alpha exists in inactive form
and several conformational changes are required during apoptosis to activate it.
Here, we have identified a novel transcript variant of Bax gene in mouse which
contains alternatively spliced new first exon that is different from the first
exon of previously reported transcript. Conceptual translation of new transcript
encodes a protein (Bax-alpha1), having different N-terminus. The existence of the
new transcript variant was confirmed by reverse transcriptase-PCR, semi-nested
PCR using primers designed for the newly identified transcript variant. The
identity of PCR product obtained after semi-nested PCR was confirmed by DNA
sequencing. Relative expression of new transcript variant with respect to
reported transcript was also studied with the help of real time PCR. The
existence of new transcript variant was further supported by the presence of
clusters of overlapping ESTs from the database. Bax-alpha1 possibly displays
heterogeneous properties as predicted by post-translational modification analysis
tools. The differences in post-translational modifications might play important
roles in divergent function of the new isoform. The three dimensional structure
was generated by homology modelling to visualize the differences at N termini of
known and newly identified variant.
PMID- 28412458
TI - Clinical significance of the B7-H4 as a novel prognostic marker in breast cancer.
AB - Increasing evidence has suggested that B7-H4 plays an important role in cancer
development not only in immune field. However, the correlation between B7-H4
protein expression and clinical outcome in primary breast cancer has not been
investigated. We examined the expression of B7-H4 by Immunohistochemistry in 147
cases of invasive breast carcinomas. Correlation of B7-H4 protein levels with
pathological tumor stages and overall survival rates of breast cancer patients
were also analyzed. Uni-and multivariate analyses methods were performed to
evaluate the prognostic value of B7-H4 expression levels. We found that different
expression levels of B7-H4 on breast cancer cells were significantly correlated
with patient's pTNM (pathological staging, T: primary tumor; N: regional lymph
node; M: distant metastasis) stage (P<0.001), overall survival (P=0.000), p53
(P=0.041). Furthermore, univariate analyses showed that the overall survival rate
of the patients with higher B7-H4 expression was significantly worse than that of
the patients with lower B7-H4 expression (P<0.001). Multivariate analyses showed
that B7-H4 was a significant independent prognostic indicator (P=0.000). Our
results suggest that B7-H4 might be closely associated with breast cancer
progression. Its high expression may serve as a potential prognostic biomarker in
human breast cancer.
PMID- 28412459
TI - No changes in heme synthesis in human Friedreich's ataxia erythroid progenitor
cells.
AB - Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced
expression of the protein frataxin. Frataxin is thought to play a role in iron
sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid
progenitor stem cells obtained from FRDA patients and healthy donors to
investigate the putative role, if any, of frataxin deficiency in heme synthesis.
We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA
quantification. We used atomic absorption spectrophotometry for iron levels and a
photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase
were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed
by a protein-protein interaction analysis was performed. FRDA patient cells
showed no significant changes in iron levels, hemoglobin synthesis,
protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis
presented 11 genes that were significantly changed in all patients compared to
controls. The genes are especially involved in oxidative stress, iron homeostasis
and angiogenesis. The mystery about the involvement of frataxin on iron
metabolism raises the question why frataxin deficiency in primary FRDA cells did
not lead to changes in biochemical parameters of heme synthesis. It seems that
alternative pathways can circumvent the impact of frataxin deficiency on heme
synthesis. We show for the first time in primary FRDA patient cells that reduced
frataxin levels are still sufficient for heme synthesis and possibly other
mechanisms can overcome reduced frataxin levels in this process. Our data
strongly support the fact that so far no anemia in FRDA patients was reported.
PMID- 28412460
TI - Characterization of transcriptome in the Indian meal moth Plodia interpunctella
(Lepidoptera: Pyralidae) and gene expression analysis during developmental
stages.
AB - The Indian meal moth Plodia interpunctella (Lepidoptera: Pyralidae) is a
worldwide pest that causes serious damage to stored foods. Although many efforts
have been conducted on this species due to its economic importance, the study of
genetic basis of development, behavior and insecticide resistance has been
greatly hampered due to lack of genomic information. In this study, we used high
throughput sequencing platform to perform a de novo transcriptome assembly and
tag-based digital gene expression profiling (DGE) analyses across four different
developmental stages of P. interpunctella (egg, third-instar larvae, pupae and
adult). We obtained approximate 9gigabyte (GB) of clean data and recovered 84,938
unigenes, including 37,602 clusters and 47,336 singletons. These unigenes were
annotated using BLAST against the non-redundant protein databases and then
functionally classified based on Gene Ontology (GO), Clusters of Orthologous
Groups (COG), and Kyoto Encyclopedia of Genes and Genomes databases (KEGG). A
large number of differentially expressed genes were identified by pairwise
comparisons among different developmental stages. Gene expression profiles
dramatically changed between developmental stage transitions. Some of these
differentially expressed genes were related to digestion and cuticularization.
Quantitative real-time PCR results of six randomly selected genes conformed the
findings in the DGEs. Furthermore, we identified over 8000 microsatellite markers
and 97,648 single nucleotide polymorphisms which will be useful for population
genetics studies of P. interpunctella. This transcriptomic information provided
insight into the developmental basis of P. interpunctella and will be helpful for
establishing integrated management strategies and developing new targets of
insecticides for this serious pest.
PMID- 28412461
TI - Effects of low-dose aspirin on maternal blood pressure and vascular function in
an experimental model of gestational hypertension.
AB - Daily intake of low-dose aspirin after 12weeks of gestation is currently
recommended as a preventative intervention in pregnancies in high risk of
developing preeclampsia. This recommendation is based on epidemiological
evidence, whereas experimental studies investigating the exact mechanisms of
aspirin action during pregnancy are lacking. We previously showed that treating
pregnant rats with a synthetic mimetic of unmethylated CpG DNA (bacterial DNA)
caused preeclampsia-like characteristics such as maternal hypertension and
increased cyclooxygenase (COX) expression and activity. In this study, we tested
the hypothesis that daily maternal treatment with low-dose aspirin would prevent
the development of maternal hypertension, reduce COX activity and thromboxane A2
(TxA2) production, and improve maternal vascular function in pregnant rats
exposed to CpG ODN during gestation. Pregnant rats were treated with ODN2395
(synthetic CpG DNA) or saline (vehicle) on gestational days (GD) 14, 16, 18.
Daily low-dose aspirin treatment (1.5mg/kgBW) started on GD10 and continued
throughout gestation. Pregnant rats treated with ODN2395 had greater systolic
blood pressure compared to controls (120+/-4mmHg vs. 100+/-5mmHg, p=0.03) and
aspirin did not prevent this increase (p=0.86). Aspirin prevented ODN2395-induced
increases of TxB2 (TxA2 metabolite) in serum and mesenteric arteries. ODN2395
increased expression of COX-1 and COX-2 in mesenteric and uterine arteries and
aspirin abolished these effects. Aspirin reduced contractile responses to
phenylephrine and U46619 (TxA2 mimetic) in mesenteric arteries from control rats
but not from ODN2395-treated rats. In conclusion, treatment with low-dose aspirin
reduced systemic and vascular COX expression and activity but did not prevent the
development of maternal hypertension induced by exposure to unmethylated CpG DNA
(bacterial DNA).
PMID- 28412462
TI - Spop regulates Gli3 activity and Shh signaling in dorsoventral patterning of the
mouse spinal cord.
AB - Sonic Hedgehog (Shh) signaling regulates the patterning of ventral spinal cord
through the effector Gli family of transcription factors. Previous in vitro
studies showed that an E3 ubiquitin ligase containing Speckle-type POZ protein
(Spop) targets Gli2 and Gli3 for ubiquitination and degradation, but the role of
Spop in Shh signaling and mammalian spinal cord patterning remains unknown. Here,
we show that loss of Spop does not alter spinal cord patterning, but it
suppresses the loss of floor plate and V3 interneuron phenotype of Gli2 mutants,
suggesting a negative role of Spop in Gli3 activator activity, Shh signaling and
the specification of ventral cell fates in the spinal cord. This correlates with
a moderate but significant increase in the level of Gli3 protein in the Spop
mutant spinal cords. Furthermore, loss of Spop restores the maximal Shh pathway
activation and ventral cell fate specification in the Gli1;Sufu double mutant
spinal cord. Finally, we show that loss of Spop-like does not change the spinal
cord patterning in either wild type or Spop mutants, suggesting that it does not
compensate for the loss of Spop in Shh signaling and spinal cord patterning.
Therefore, our results demonstrate a negative role of Spop in the level and
activity of Gli3, Shh signaling and ventral spinal cord patterning.
PMID- 28412463
TI - A methodological survey identified eight proposed frameworks for the adaptation
of health related guidelines.
AB - BACKGROUND AND OBJECTIVE: Our objective was to identify and describe published
frameworks for adaptation of clinical, public health, and health services
guidelines. METHODS: We included reports describing methods of adaptation of
guidelines in sufficient detail to allow its reproducibility. We searched Medline
and EMBASE databases. We also searched personal files, as well manuals and
handbooks of organizations and professional societies that proposed methods of
adaptation and adoption of guidelines. We followed standard systematic review
methodology. RESULTS: Our search captured 12,021 citations, out of which we
identified eight proposed methods of guidelines adaptation: ADAPTE, Adapted
ADAPTE, Alberta Ambassador Program adaptation phase, GRADE-ADOLOPMENT, MAGIC,
RAPADAPTE, Royal College of Nursing (RCN), and Systematic Guideline Review (SGR).
The ADAPTE framework consists of a 24-step process to adapt guidelines to a local
context taking into consideration the needs, priorities, legislation, policies,
and resources. The Alexandria Center for Evidence-Based Clinical Practice
Guidelines updated one of ADAPTE's tools, modified three tools, and added three
new ones. In addition, they proposed optionally using three other tools. The
Alberta Ambassador Program adaptation phase consists of 11 steps and focused on
adapting good-quality guidelines for nonspecific low back pain into local
context. GRADE-ADOLOPMENT is an eight-step process based on the GRADE Working
Group's Evidence to Decision frameworks and applied in 22 guidelines in the
context of national guideline development program. The MAGIC research program
developed a five-step adaptation process, informed by ADAPTE and the GRADE
approach in the context of adapting thrombosis guidelines. The RAPADAPTE
framework consists of 12 steps based on ADAPTE and using synthesized evidence
databases, retrospectively derived from the experience of producing a high
quality guideline for the treatment of breast cancer with limited resources in
Costa Rica. The RCN outlines five key steps strategy for adaptation of guidelines
to the local context. The SGR method consists of nine steps and takes into
consideration both methodological gaps and context-specific normative issues in
source guidelines. We identified through searching personal files two abandoned
methods. CONCLUSION: We identified and described eight proposed frameworks for
the adaptation of health-related guidelines. There is a need to evaluate these
different frameworks to assess rigor, efficiency, and transparency of their
proposed processes.
PMID- 28412465
TI - Authors of clinical trials reported individual and financial conflicts of
interest more frequently than institutional and nonfinancial ones: a
methodological survey.
AB - BACKGROUND AND OBJECTIVE: Conflicts of interest (COIs) are increasingly
recognized as important to disclose and manage in health research. The objective
of this study was to assess the reporting of both financial and nonfinancial COI
by authors of randomized controlled trials published in a representative sample
of clinical journals. METHODS: We searched Ovid Medline and included a random
sample of 200 randomized controlled trials published in 2015 in one of the 119
Core Clinical Journals. We classified COI using a comprehensive framework that
includes the following: individual COIs (financial, professional, scholarly,
advocatory, personal) and institutional COIs (financial, professional, scholarly,
and advocatory). We conducted descriptive and regression analyses. RESULTS: Of
the 200 randomized controlled trials, 188 (94%) reported authors' COI disclosures
that were available in the main document (92%) and as International Committee of
Medical Journal Editors forms accessible online (12%). Of the 188 trials, 57% had
at least one author reporting at least one COI; in all these trials, at least one
author reported financial COI. Institutional COIs (11%) and nonfinancial COIs
(4%) were less commonly reported. References to COI disclosure statements for
editors (1%) and medical writers (0%) were seldom present. Regression analyses
showed positive associations between reporting individual financial COI and
higher journal impact factor (odds ratio [OR] = 1.06, 95% confidence interval
[CI] = 1.02-1.10), larger number of authors (OR = 1.10, 95% CI 1.02-1.20),
affiliation with an institution from a high-income country (OR = 16.75, 95% CI
3.38-82.87), and trials reporting on pharmacological interventions (OR = 2.28,
95% CI 1.13-4.62). CONCLUSION: More than half of published randomized controlled
trials report that at least one author has a COI. Trial authors report financial
COIs more often than nonfinancial COIs and individual COIs more frequently than
institutional COIs.
PMID- 28412464
TI - GRADE equity guidelines 1: considering health equity in GRADE guideline
development: introduction and rationale.
AB - OBJECTIVES: This article introduces the rationale and methods for explicitly
considering health equity in the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) methodology for development of clinical,
public health, and health system guidelines. STUDY DESIGN AND SETTING: We
searched for guideline methodology articles, conceptual articles about health
equity, and examples of guidelines that considered health equity explicitly. We
held three meetings with GRADE Working Group members and invited comments from
the GRADE Working Group listserve. RESULTS: We developed three articles on
incorporating equity considerations into the overall approach to guideline
development, rating certainty, and assembling the evidence base and evidence to
decision and/or recommendation. CONCLUSION: Clinical and public health guidelines
have a role to play in promoting health equity by explicitly considering equity
in the process of guideline development.
PMID- 28412466
TI - Proposed variations of the stepped-wedge design can be used to accommodate
multiple interventions.
AB - OBJECTIVES: Stepped-wedge design (SWD) cluster-randomized trials have
traditionally been used for evaluating a single intervention. We aimed to explore
design variants suitable for evaluating multiple interventions in an SWD trial.
STUDY DESIGN AND SETTING: We identified four specific variants of the traditional
SWD that would allow two interventions to be conducted within a single cluster
randomized trial: concurrent, replacement, supplementation, and factorial SWDs.
These variants were chosen to flexibly accommodate study characteristics that
limit a one-size-fits-all approach for multiple interventions. RESULTS: In the
concurrent SWD, each cluster receives only one intervention, unlike the other
variants. The replacement SWD supports two interventions that will not or cannot
be used at the same time. The supplementation SWD is appropriate when the second
intervention requires the presence of the first intervention, and the factorial
SWD supports the evaluation of intervention interactions. The precision for
estimating intervention effects varies across the four variants. CONCLUSION:
Selection of the appropriate design variant should be driven by the research
question while considering the trade-off between the number of steps, number of
clusters, restrictions for concurrent implementation of the interventions,
lingering effects of each intervention, and precision of the intervention effect
estimates.
PMID- 28412467
TI - Magnitude and direction of missing confounders had different consequences on
treatment effect estimation in propensity score analysis.
AB - OBJECTIVE: Propensity score (PS) analysis allows an unbiased estimate of
treatment effects but assumes that all confounders are measured. We assessed the
impact of omitting confounders from a PS analysis on clinical decision making.
STUDY DESIGN AND SETTING: We conducted Monte Carlo simulations on hypothetical
observational studies based on virtual populations and on the population from a
large randomized trial (CRASH-2). In both series of simulations, PS analysis was
conducted with all confounders and with omitted confounders, which were defined
to have different strengths of association with the outcome and treatment
exposure. After inverse probability of treatment weighting, we calculated the
absolute risk differences and numbers needed to treat (NNT). RESULTS: In both
series of simulations, omitting a confounder that was moderately associated with
the outcome and exposure led to negligible bias on the NNT scale. The bias
induced by omitting strongly positive confounding variables remained less than 15
patients to treat. Major bias and reversed effects were found only when omitting
highly prevalent, strongly negative confounders that were similarly associated
with the outcome and exposure with odds ratios greater than 4.00 (or <0.25). This
omission was accompanied by a substantial decrease in analysis power. CONCLUSION:
The omission of strongly negative confounding variables from a PS analysis can
lead to incorrect clinical decision making. However, omitting these variables
also decreases the analysis power, which may prevent the reporting of significant
but misleading effects.
PMID- 28412468
TI - A computationally simple central monitoring procedure, effectively applied to
empirical trial data with known fraud.
AB - OBJECTIVES: Central monitoring of multicenter clinical trials becomes an ever
more feasible quality assurance tool, in particular for the detection of data
fabrication. More widespread application, across both industry sponsored as well
as academic clinical trials, requires central monitoring methodologies that are
both effective and relatively simple in implementation. STUDY DESIGN AND SETTING:
We describe a computationally simple fraud detection procedure intended to be
applied repeatedly and (semi-)automatically to accumulating baseline data and to
detect data fabrication in multicenter trials as early as possible. The procedure
is based on anticipated characteristics of fabricated data. It consists of seven
analyses, each of which flags approximately 10% of the centers. Centers that are
flagged three or more times are considered "potentially fraudulent" and require
additional investigation. The procedure is illustrated using empirical trial data
with known fraud. RESULTS: In the illustration data, the fraudulent center is
detected in most repeated applications to the accumulating trial data, while
keeping the proportion of false-positive results at sufficiently low levels.
CONCLUSION: The proposed procedure is computationally simple and appears to be
effective in detecting center-level data fabrication. However, assessment of the
procedure on independent trial data sets with known data fabrication is required.
PMID- 28412470
TI - Crosstalk between kidney and bone - Bench to bedside.
PMID- 28412469
TI - Earliest phases of chondrogenesis are dependent upon angiogenesis during ectopic
bone formation in mice.
AB - Endochondral ossification is the process where cartilage forms prior to
ossification and in which new bone forms during both fracture healing and ectopic
bone formation. Transitioning to ossification is a highly coordinated process
between hypertrophic chondrocytes, vascular endothelial cells, osteoblasts and
osteoclasts. A critical biological process that is central to the interactions of
these various cell types is angiogenesis. Although it is well established that
angiogenesis is crucial for fracture repair, less is known pertaining to the role
of angiogenesis in ectopic bone formation. Furthermore, fracture repair models
are complicated by extensive trauma, subsequent inflammatory responses and
concurrent repair processes in multiple tissues. In order to more definitively
characterize the relationship between angiogenesis and postnatal endochondral
ossification, a model of ectopic bone formation was used. Human demineralized
bone matrix (DBM) was implanted in immune-deficient mice (rag null (B6.129S7
Rag1tm1/MOM/J)) to induce ectopic bone. Inhibition of angiogenesis with either a
small molecule (TNP-470) or a targeted biological (Vascular Endothelial Growth
Factor Receptor type 2 [VEGFR2] blocking antibody) prevented ectopic bone
formation by 83% and 77%, respectively. Most striking was that the progression of
chondrogenesis was halted during very early phases of chondrocyte differentiation
between condensation and prehypertrophy (TNP-470) or the proliferative phase
(VEGFR2 blockade) prior to hypertrophy, while osteoclast recruitment and
resorption were almost completely inhibited. Our results demonstrate angiogenesis
plays a developmental role in endochondral bone formation at a much earlier phase
of chondrogenesis than suggested by prior findings.
PMID- 28412471
TI - Surface modification of solid lipid nanoparticles for oral delivery of curcumin:
Improvement of bioavailability through enhanced cellular uptake, and lymphatic
uptake.
AB - Curcumin has been reported to exhibit potent anticancer effects. However, poor
solubility, bioavailability and stability of curcumin limit its in vivo efficacy
for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising
delivery system for the enhancement of bioavailability of hydrophobic drugs.
However, burst release of drug from SLN in acidic environment limits its usage as
oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated
curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic
environment and enhance the bioavailability. The NCC-SLN exhibited suppressed
burst release in simulated gastric fluid while sustained release was observed in
simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity
and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability
of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin
solution, respectively. These results suggest that NCC-SLN could be an efficient
oral delivery system for curcumin.
PMID- 28412472
TI - Preparation and characterization of dutasteride-loaded nanostructured lipid
carriers coated with stearic acid-chitosan oligomer for topical delivery.
AB - Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair
growth. To enhance delivery to the hair follicles and reduce systemic effects, in
this study dutasteride has been formulated for topical application, in a
nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid
(CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1H NMR and
FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs)
was optimized using a 23 full factorial design. This formulation was coated with
different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with
5% SA-CSO increased mean size from 187.6+/-7.0nm to 220.1+/-11.9nm, and modified
surface charge, with zeta potentials being -18.3+/-0.9mV and +25.8+/-1.1mV for
uncoated and coated DST-NLCs respectively. Transmission electron microscopy
showed all formulations comprised approximately spherical particles. DST-NLCs,
coated and uncoated with CSO-SA, exhibited particle size stability over 60days,
when stored at 4-8 degrees C. However, NLCs coated with CSO (without conjugation)
showed aggregation when stored at 4-8 degrees C after 30days. The measured
particle size for all formulations stored at 25 degrees C suggested aggregation,
which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All
nanoparticle formulations exhibited rapid release in an in vitro release study,
with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion
cell, no dutasteride permeated through pig ear skin after 48h, such that it was
not detected in the receptor chamber for all samples. The amount of dutasteride
in the skin was significantly different (p<0.05) for DST-NLCs (6.09+/
1.09MUg/cm2) without coating and those coated with 5% CSO-SA (2.82+/
0.40MUg/cm2), 10% CSO-SA (2.70+/-0.35MUg/cm2) and CSO (2.11+/-0.64MUg/cm2). There
was a significant difference (p<0.05) in the cytotoxicity (IC50) between
dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO
SA increased the maximum non-toxic concentration by 20-fold compared to
dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate
was successfully prepared, and modified the surface charge of DST-NLCs from
negative to positive. These stable, less cytotoxic, positively-charged
dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan
oligomer conjugate, are appropriate for topical delivery and have potential for
promotion of hair growth.
PMID- 28412473
TI - Nanoformulations for dimethyl fumarate: Physicochemical characterization and in
vitro/in vivo behavior.
AB - Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple
sclerosis treatment (Tecfidera(r)). Nevertheless, since Tecfidera(r) capsules
induce flushing, gastro-intestinal events and other more serious drawbacks, in
this investigation a nanoparticle based system to be administered by an
alternative way is proposed. In particular this study describes the preparation
and characterization of dimethyl fumarate-containing solid lipid nanoparticles
(SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80
and cationic SLN constituted of tristearin in mixture with
dimethyldioctadecylammonium chloride were investigated. The effect of the
presence of dimethyl fumarate, functionalization by polysorbate 80 and
dimethyldioctadecylammonium chloride was studied on morphology and dimensional
distribution of SLN, by photon correlation spectroscopy and cryogenic
transmission electron microscopy. Dimethyl fumarate release from SLN, studied by
Franz cell, evidenced a Fickian dissolutive type kinetic in the case of SLN
treated by polysorbate 80. Moreover fluorescent SLN were produced and
characterized in order to investigate their in vitro permeability and in vivo
biodistribution in mice. An in vitro study of fluorescent SLN permeability
performed through a model of mouse brain microvascular endothelial cells,
indicated that cationic SLN displayed higher permeability values with respect to
neutral SLN and SLN treated by polysorbate 80. Biodistribution of polysorbate 80
treated SLN was studied by fluorescent imaging after intraperitoneal or
intranasal administration in mice. The in vivo images indicate that polysorbate
80 treated SLN were able to reach the brain, even if they prevalently accumulated
in liver and spleen, especially by intraperitoneal route.
PMID- 28412474
TI - Kinetics for Drug Discovery: an industry-driven effort to target drug residence
time.
AB - A considerable number of approved drugs show non-equilibrium binding
characteristics, emphasizing the potential role of drug residence times for in
vivo efficacy. Therefore, a detailed understanding of the kinetics of association
and dissociation of a target-ligand complex might provide crucial insight into
the molecular mechanism-of-action of a compound. This deeper understanding will
help to improve decision making in drug discovery, thus leading to a better
selection of interesting compounds to be profiled further. In this review, we
highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium,
which targets major open questions related to binding kinetics in an industry
driven public-private partnership.
PMID- 28412476
TI - Monoclonal gammopathy of undetermined significance and biological treatments:
What should we do?
PMID- 28412475
TI - Potential anti-inflammatory effect of LQFM-021 in carrageenan-induced
inflammation: The role of nitric oxide.
AB - The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti
inflammatory activities. Furthermore, it has low toxicity, indicating that this
compound may be considered to be a good prototype for the development of new
analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to
investigate the potential anti-inflammatory activity of LQFM-021 using a model of
carrageenan-induced inflammation as well as the mechanism of action and role of
nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg
p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan
injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.)
reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as
decreased protein extravasation and myeloperoxidase activity. This dose of LQFM
021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF
alpha and IL-1beta levels in the pleural cavity. Moreover, pre-treatment with L
NAME reversed the effect of LQFM-021 on NO, leukocyte migration, and the TNF
alpha and IL-1beta levels. Additionally, we observed that LQFM-021 showed weak
inhibitory activity on cyclooxygenases, but reduced the PGE2 levels in the
pleural cavity. Immunoblot analyses showed that LQFM-021 promoted a decrease in
COX-2 levels and increase in iNOS levels. In conclusion, we demonstrated that
LQFM-021 has marked anti-inflammatory activity by reducing polymorphonuclear
recruitment, which is associated with the inhibition of the production of
inflammatory cytokines and eicosanoids. In addition, we found that the
synthase/release of nitric oxide promoted by LQFM-021 is essential for the anti
inflammatory effect observed.
PMID- 28412477
TI - Impact of major life events on breast-cancer-specific mortality: A case fatality
study on 8000 breast cancer patients.
AB - BACKGROUND: It has been suggested that long-term activation of the body's stress
response system and subsequent overexposure to stress hormones may be associated
with increased morbidity. However, evidence on the impact of major life events on
mortality from breast cancer (BC) remains inconclusive. The main aim of this
study is to investigate whether major negatively or positively experienced life
events before or after diagnosis have an effect on BC-specific mortality in women
who have survived with BC for at least 2 years. METHODS: We conducted a case
fatality study with data on life events from a self-administered survey and data
on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC
mortality hazard ratios (MRs) between those who have undergone major life events
and those who haven't. RESULTS: None of the pre-diagnostic negative life events
had any effect on BC-specific mortality. Regarding post-diagnostic events, the
effect was greatest in women with moderate scores of events. As for event
specific scores, increased BC mortality was observed with spouse unemployment,
relationship problems, and death of a close friend. By contrast, falling in love
and positive developments in hobbies were shown to be associated with lower BC
mortality (MRs 0.67, 95%CI: 0.49-0.92 and 0.74, 95%CI: 0.57-0.96, respectively).
In an analysis restricted to recently diagnosed cases (2007), also death of a
child and of a mother was associated with increased BC mortality. CONCLUSIONS:
Some major life events regarding close personal relationships may play a role in
BC-specific mortality, with certain negative life events increasing BC mortality
and positive events decreasing it. The observed favorable associations between
positive developments in romantic relationships and hobbies and BC mortality are
likely to reflect the importance of social interaction and support.
PMID- 28412478
TI - Mitochondrial and peroxisomal Lon proteases play opposing roles in reproduction
and growth but co-function in the normal development, stress resistance and
longevity of Thermomyces lanuginosus.
AB - The ATP-dependent Lon enzyme is a highly conserved protease with multiple roles
in diverse species such as fungi; however, there are few reports on Lon enzymes
in filamentous fungi. Thermomyces lanuginosus, a typical thermophilic fungus, has
been widely studied in physiology and cell biology; thus, studies on Thermomyces
Lons are important. Two Lons were bioinformatically deduced in T. lanuginosus.
Subcellular localization analysis showed that one is present in mitochondria
(MLon), while the other is found in peroxisomes (PLon). Although both Lon enzymes
were activated by H2O2, they were not induced by heat shock; instead, they were
induced by low temperatures. Two single-deletion Lon mutants (DeltaMLon and
DeltaPLon) were generated. Biological analysis demonstrated that DeltaMLon
decreased the production of conidia but increased the growth of mycelia. By
contrast, DeltaPLon increased the production of conidia but decreased the growth
of mycelia. The lifespan was measured in time and in length of continuous growth.
The wild-type strain showed continuous linear growth for 60days, whereas growth
was impeded at 30 and 50days for DeltaPLon and DeltaMLon mutants, respectively,
suggesting that PLon is more important for longevity than MLon. Interestingly,
DeltaPLon, which accumulated larger amount of H2O2 was not only more sensitive to
exogenous H2O2 but also much more sensitive to other selected stressors. Taken
together, our data indicate that mitochondrial and peroxisomal Lons play opposite
roles in controlling growth and development, but exhibit synergistic effects on
the normal states of vegetative growth, asexual development, stress resistance
and longevity in T. lanuginosus.
PMID- 28412479
TI - Cough in exercise and athletes.
AB - Cough is the most common respiratory symptom reported by athletes and can
significantly impact on health status, ability to train and athletic performance.
The presence of cough in an athlete is typically taken to indicate exercise
induced bronchoconstriction (EIB), yet in many athletes with chronic cough there
is no objective evidence of airway hyper-responsiveness (AHR) or heightened
airway inflammation. Moreover, cough in athletes often fails to respond to a
therapeutic asthma strategy, thus further work is urgently needed to progress our
understanding of the pathophysiology of exercise-associated cough in this unique
population. This article provides an overview of the current state of knowledge
of exercise-associated cough in athletes. The article summarises our
understanding of pathophysiological basis of cough in this context and provides a
pragmatic clinical approach to this problem.
PMID- 28412480
TI - Retraction of Neurosurgical Publications: A Systematic Review.
AB - OBJECTIVES: Despite the increasing awareness of scientific fraud, no attempt has
been made to assess its prevalence in neurosurgery. The aim of our review was to
assess the chronologic trend, reasons, research type/design, and country of
origin of retracted neurosurgical publications. METHODS: Three independent
reviewers searched the EMBASE and MEDLINE databases using neurosurgical keywords
for retracted articles from 1995 to 2016. Archives of retracted articles
(retractionwatch.com) and the independent Web sites of neurosurgical journals
were also searched. Data including the journal, impact factor, reason for
retraction, country of origin, and citations were extracted. RESULTS: A total of
97 studies were included for data extraction. Journal impact factor ranged from
0.57 to 35.03. Most studies (61) were retracted within the last 5 years. The most
common reason for retraction was because of a duplicated publication found
elsewhere (26), followed closely by plagiarism (22), or presenting fraudulent
data (14). Other reasons included scientific errors/mistakes, author
misattribution, and compromised peer review. Articles originated from several
countries and some were widely cited. CONCLUSIONS: Retractions of neurosurgical
publications are increasing significantly, mostly because of issues of academic
integrity, including duplicate publishing and plagiarism. Implementation of more
transparent data-sharing repositories and thorough screening of data before
manuscript submission, as well as additional educational programs for new
researchers, may help mitigate these issues in the future.
PMID- 28412481
TI - Environmental and Clinical Risk Factors for Delirium in a Neurosurgical Center: A
Prospective Study.
AB - BACKGROUND: Few reports of delirium-related risk factors have focused on
environmental risk factors and clinical risk factors, such as white matter signal
abnormalities on magnetic resonance imaging fluid attenuated inversion recovery
images. METHODS: We prospectively enrolled 253 patients admitted to our
neurosurgical center between December 2014 and June 2015 and analyzed 220
patients (100 male patients; mean age, 64.1 years; age range, 17-92 years). An
Intensive Care Delirium Screening Checklist score >=4 points indicated delirium.
We evaluated patient factors consisting of baseline characteristics and related
factors, such as white matter lesions (WMLs), as well as the surrounding
environment. RESULTS: Delirium occurred in 29/220 cases (13.2%). Regarding
baseline characteristics, there were significant statistical correlations between
delirium and age (P = 0.0187), Hasegawa Dementia Scale-Revised score (P = 0.0022)
on admission, and WMLs (P < 0.0001). WMLs were related to age (P < 0.0001) and
atherosclerotic disease (P = 0.004). Regarding related factors, there were
significant statistical correlations between delirium and stay in a neurosurgical
care unit (P = 0.0245). Multivariate logistic regression analyses showed
statistically significant correlations of delirium with WMLs (P < 0.0001) and
surrounding patients with delirium (P = 0.026). CONCLUSIONS: WMLs in patients and
the surrounding environment are risk factors for delirium in a neurosurgical
center. To prevent delirium, clinicians must recognize risk factors, such as high
grade WMLs, and manage environmental factors.
PMID- 28412482
TI - Dapagliflozin-citric acid cocrystal showing better solid state properties than
dapagliflozin.
AB - Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2
inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO
H2O, 1:1:1) is the solid form used in the current tablet product to address the
severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the
problem of instability when exposed to high temperature, which renders it
amorphous. In this work, we report on the preparation and evaluation of a new 1:1
cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits
superior stability against high temperature and high relative humidity without
compromising dissolution and tableting performance. Thus, DAP-CA is a promising
solid form for developing the next generation DAP tablet products with improved
performance.
PMID- 28412483
TI - Effect of micro-environment modification and polymer type on the in-vitro
dissolution behavior and in-vivo performance of amorphous solid dispersions.
AB - This study investigates the effects of micro-environment modification and polymer
type on the in-vitro dissolution behavior and in-vivo performance of micro
environment pH modifying solid dispersions (pHM-SD) for the poorly water-soluble
model drug Toltrazuril (TOL). Various pHM-SDs were prepared using Ca(OH)2 as a pH
modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000),
polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based
on the results of physicochemical characterizations and in-vitro dissolution
testing, the representative ternary (Ca(OH)2:TOL:PEG6000/HPMC/PVPk30=1:8:24,
w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and
optimized to perform in-vivo pharmacokinetic study. The micro-environment pH
modification improved the in-vitro water-solubility and in-vivo bioavailability
of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the
release and absorption of prototype drug, but also promoted the generation of
active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril
sulfone (TOLSO2). The in-vitro dissolution profiles and in-vivo absorption,
distribution and metabolism behaviors of the pHM-SDs varied with polymer type.
Moreover, in-vivo bioavailability of three active pharmaceutical ingredients
increased with an increase in in-vitro dissolution rates of the drug from the pHM
SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution
method can be used to predict the in-vivo performance of pHM-SDs formulated with
various polymers with trend consistency. In-vitro and in-vivo screening
procedures revealed that the pHM-SD composed of Ca(OH)2, TOL and PVPk30 at a
weight ratio of 1:8:24, of which the safety was adequately proved via
histopathological examination, may be a promising candidate for providing better
clinical outcomes.
PMID- 28412484
TI - Impact of demographics and disease progression on the relationship between
glucose and HbA1c.
AB - CONTEXT: Several studies have shown that the relationship between mean plasma
glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations.
Especially race has previously been referred to shift the regression line that
links MPG to HbA1c at steady-state (Herman & Cohen, 2012). OBJECTIVE: To assess
the influence of demographic and disease progression-related covariates on the
intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.
DATA: Longitudinal patient-level data from 16 late-phase trials in type 2
diabetes with a total of 8927 subjects was used to study covariates for the
relationship between MPG and HbA1c. The analysed covariates included age group,
BMI, gender, race, diabetes duration, and pre-trial treatment. Differences
between trials were taken into account by estimating a trial-to-trial variability
component. PARTICIPANTS: Participants included 47% females and 20% above 65years.
77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were
analysed together as other races. ANALYSIS: Estimates of the change in the
intercept of the MPG-HbA1c relationship due to the mentioned covariates were
determined using a longitudinal model. RESULTS: The analysis showed that pre
trial treatment with insulin had the most pronounced impact associated with a
0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group
also had an impact on the MPG-HbA1c relationship. CONCLUSION: Our analysis shows
that the relationship between MPG and HbA1c is relatively insensitive to
covariates, but shows small variations across populations, which may be relevant
to take into account when predicting HbA1c response based on MPG measurements in
clinical trials.
PMID- 28412485
TI - Cancer nanotheranostics: A review of the role of conjugated ligands for
overexpressed receptors.
AB - Cancer treatment using chemotherapy has many drawbacks because of its non
specificity, in which the chemotherapeutic agent attacks both normal and
cancerous cells, leading to severe damage to the normal cells, especially rapidly
proliferating ones. Cancer targeting enables the drug to kill only tumor cells
without adversely affecting healthy tissues, which leads to the improvement of
the patient's well-being. Nanoparticles offer several advantages in drug delivery
such as enhancing the solubility of hydrophobic drugs, sustaining their release
and prolonging their circulation time. The ability of nanoparticles to
specifically target tumor cells makes them a useful delivery system for
anticancer agents. The type of the delivery system and formulation additives used
can also improve the delivery of the anticancer agent. This review highlights
some of the most highly sought receptors to be targeted in selective cancer
treatment. It also reports some of the recent advances in cancer targeting using
drug-loaded ligand-conjugated nanocarriers.
PMID- 28412486
TI - Removal of toxic metals from vanadium-contaminated soils using a washing method:
Reagent selection and parameter optimization.
AB - Vanadium (V) contamination in soils is an increasing worldwide concern facing
human health and environmental conservation. The fractionation of a metal
influences its mobility and biological toxicity. We analyzed the fractionations
of V and several other metals using the BCR three-step sequential extraction
procedure. Among methods for removing metal contamination, soil washing is an
effective permanent treatment. We conducted experiments to select the proper
reagents and to optimize extraction conditions. Citric acid, tartaric acid,
oxalic acid, and Na2EDTA all exhibited high removal rates of the extractable
state of V. With a liquid-to-solid ratio of 10, washing with 0.4 mol/L citric
acid, 0.4 mol/L tartaric acid, 0.4 mol/L oxalic acid, and 0.12 mol/L Na2EDTA led
to removal rates of 91%, 88%, 88%, and 61%, respectively. The effect of multiple
washing on removal rate was also explored. According to the changes observed in
metal fractionations, differences in removal rates among reagents is likely
associated with their pKa value, pH in solution, and chemical structure. We
concluded that treating with appropriate washing reagents under optimal
conditions can greatly enhance the remediation of vanadium-contaminated soils.
PMID- 28412487
TI - Occurrence, homologue patterns and source apportionment of short- and medium
chain chlorinated paraffins in suburban soils of Shanghai, China.
AB - In order to systematically investigate the spatial distribution, homologue
profiles, and sources of short- and medium-chain chlorinated paraffins (SCCPs and
MCCPs) in suburban soils in Shanghai, SCCPs and MCCPs in soils were analyzed
using gas chromatography coupled with low resolution mass spectrometry in
electron capture negative ion (ECNI) mode (GC-ECNI-MS). The CP concentrations in
soils were between not detected (ND) - 697 ng g-1 with a median value of 3.52 ng
g-1 for SCCPs, and ND - 666 ng g-1 with a median value of 15.3 ng g-1 for MCCPs,
respectively. The concentrations of MCCPs in most soils were higher than that of
SCCPs. The total CP concentrations (sum of SCCPs and MCCPs) in soils varied from
ND to 964 ng g-1 with a median value of 20.5 ng g-1. The concentration of MCCPs
was higher than that of SCCPs in most soils. The levels of SCCPs and MCCPs in
suburban soils in Shanghai were at the medium level when compared to other areas
around the world. No significant correlation was observed between soil CP
concentrations and total organic carbon contents (p > 0.05). For different use
type of soils, the median concentrations of CPs in soils were found higher in
greenland than that in other areas probably due to busy traffic, sewage sludge
application and/or wastewater irrigation. All soils were divided into two groups
by hierarchical cluster analysis (HCA) both for SCCPs and MCCPs. Three discharge
sources of CPs in suburban soil of Shanghai were identified by PMF model.
PMID- 28412488
TI - In vitro cytotoxicity of decabrominated diphenyl ether (PBDE-209) to human red
blood cells (hRBCs).
AB - This work presents the effect of decabrominated diphenyl ether (PBDE-209) on the
anti-oxidative defense capacity, and ATPase activity (structure and function) of
human red blood cells (hRBCs). The results show that the PBDE-209 influences the
activity and content of typical biomolecules (SOD, CAT, GSH-Px, GSH and MDA) in
hRBCs, causing a decline in the function of the antioxidant defense system. The
PBDE-209 with a concentration of 10 MUmol/L resulted in the cytoplasmic
projections and structure deformation of the hRBCs. When its concentration
exceeds 25 MUmol/L, the relative ATPase activity was decreased to 20% of the
initial activity. Since the discovered effects of PBDE-209 on hRBCs are in cell
level, this study may offer some information to advise the related in vivo
cytotoxicity works.
PMID- 28412489
TI - Bimetallic AgCu/Cu2O hybrid for the synergetic adsorption of iodide from
solution.
AB - To further improve the capacity of Cu2O to absorb I- anions from solution, and to
understand the difference between the adsorption mechanisms of Ag/Cu2O and
Cu/Cu2O adsorbents, bimetallic AgCu was doped into Cu2O through a facile
solvothermal route. Samples were characterized and employed to adsorb I- anions
under different experimental conditions. The results show that the Cu content can
be tuned by adding different volumes of Ag sols. After doping bimetallic AgCu,
the adsorption capacity of the samples can be increased from 0.02 mmol g-1 to
0.52 mmol g-1. Moreover, the optimal adsorption is reached within only 240 min.
Meanwhile, the difference between the adsorption mechanisms of Ag/Cu2O and
Cu/Cu2O adsorbents was verified, and the cooperative adsorption mechanism of the
AgCu/Cu2O hybrid was proposed and verified. In addition, the AgCu/Cu2O hybrid
showed excellent selectivity, e.g., its adsorption efficiencies are 85.1%, 81.9%,
85.9% and 85.7% in the presence of the Cl-, CO32-, SO42- and NO3- competitive
anions, respectively. Furthermore, the AgCu/Cu2O hybrid can worked well in other
harsh environments (e.g., acidic, alkaline and seawater environments). Therefore,
this study is expected to promote the development of Cu2O into a highly efficient
adsorbent for the removal of iodide from solution.
PMID- 28412490
TI - Serpentine soils affect heavy metal tolerance but not genetic diversity in a
common Mediterranean ant.
AB - Natural habitats with serpentine soils are rich in heavy metal ions, which may
significantly affect ecological communities. Exposure to metal pollutants
results, for instance, in a reduction of population genetic diversity and a
diffused higher tolerance towards heavy metals. In this study, we investigated
whether chronic exposure to metals in serpentine soils affect accumulation
patterns, tolerance towards metal pollutants, and genetic diversity in ants. In
particular, we studied colonies of the common Mediterranean ant, Crematogaster
scutellaris, along a contamination gradient consisting of two differently
contaminated forests and a reference soil with no geogenic contamination. We
first evaluated the metal content in both soil and ants' body. Then, we tested
for tolerance towards metal pollutants by evaluating the mortality of ants fed
with nickel (Ni) solutions of increasing concentrations. Finally, differences in
genetic diversity among ants from different areas were assessed using eight
microsatellite loci. Interestingly, a higher tolerance to nickel solutions was
found in ants sampled in sites with intermediate levels of heavy metals. This may
occur, because ants inhabiting strongly contaminated areas tend to accumulate
higher amounts of contaminants. Additional ingestion of toxicants beyond the
saturation threshold would lead to death. There was no difference in the genetic
diversity among ant colonies sampled in different sites. This was probably the
result of queen mediated gene flow during nuptial flights across uncontaminated
and contaminated areas of limited geographical extent.
PMID- 28412491
TI - Rapid degradation of atrazine by hydroxyl radical induced from montmorillonite
templated subnano-sized zero-valent copper.
AB - In this study, subnano-sized zero-valent copper (ZVC) was synthesized using
montmorillonite clay mineral as the template. The discrete distribution of
surface charge on montmorillonite effectively separates the formed ZVC particles
and inhibits their aggregation. X-ray diffraction result indicates that the size
of ZVC particles on montmorillonite is ~6 A, which is much smaller than nano-ZVC
prepared by conventional method. The montmorillonite templated ZVC (ZVCMMT) shows
superior reactivity as indicated by the degradation of atrazine, over 90%
atrazine (15 MUM) could be degraded in a few min. Hydroxyl radical is confirmed
as the reactive species, which is produced from the activation of oxygen by ZVC.
It was also shown that the degradation process is strongly dependent on the
hydration status of synthesized ZVCMMT. The freeze dried ZVCMMT exhibits higher
reactivity compared to freshly prepared ZVCMMT, which can be explained by the
higher adsorption of atrazine and oxygen residue on freeze dried ZVCMMT surface.
In addition, the toxicity of atrazine is significantly decreased after the
reaction with ZVCMMT, indicating that ZVCMMT could be used as a promising
material for rapid remediation of persistent organic contaminants.
PMID- 28412492
TI - Element variability in lacustrine systems of Terra Nova Bay (Antarctica) and
concentration evolution in surface waters.
AB - Major, minor and trace elements were determined in freshwater of lacustrine
systems in Terra Nova Bay, along Victoria Land coast, Antarctica, as well as in
algae and mosses. The samples were collected during some of the sampling
campaigns between 2007 and 2011 (and the one of 2002) within the framework of the
Italian National Program of Research in Antarctica (PNRA). Data were processed
with chemometric techniques. Results showed that elements typically considered as
potential anthropogenic pollutants (e.g. As, Pb, Zn, Cu and Ni) present a strong
correlation with the lithogenic elements (e.g. Al, Si, Fe) in all matrices,
suggesting that their origin is connected to natural phenomena. Metal
concentrations in vegetation samples are in the same range as previously
published data. The obtained results were compared with older literature data
(since the early '90s) from the same lacustrine systems, in order to present a
historical overview of element concentrations. This approach furnishes important
information on surface water evolution as a function of time. A considerable
variability was observed in metal concentrations but no clear trend was
identified. This suggests that their concentration evolution is hardly correlated
to specific natural or anthropic phenomena. No evidence of an increase of
concentrations over time was apparent. Our results represent new important data
about metal concentrations in lacustrine systems in Antarctica, furnishing ranges
of values that can be considered as a reference. These data, therefore, could be
used to detect or monitor future local and/or global anthropogenic
contaminations.
PMID- 28412493
TI - The clinical impact and prevalence of emergency point-of-care ultrasound: A
prospective multicenter study.
AB - OBJECTIVE: The main objectives of our study were to evaluate the prevalence of
emergency point-of-care ultrasound (POCUS) use and to assess the impact of POCUS
on: diagnostic, therapeutic, patient orientation and imaging practices. METHODS:
This was a one-day, prospective, observational study carried out across multiple
centers. Fifty emergency departments (EDs) recorded all POCUS performed over a
24h period. The prevalence of POCUS was defined as the number of POCUS/number of
patients seen in all units. The "diagnostic impact" was defined as a POCUS
induced confirmation or change to the initial clinical diagnosis. The
"therapeutic impact" was defined as a POCUS-induced change in treatment. The
"orientation impact" was defined as an ultrasound-induced confirmation or change
in the initial orientation. The "imaging change" was defined as a radiologic
imaging prescription modification. RESULTS: Two hundred and twenty-nine (5%)
POCUS were performed on 192 patients (4%) from among the 4671 patients seen on
the study day in the 50 EDs. No ultrasound procedural guidance was given during
the study day. The diagnostic, therapeutic and orientation impacts were
respectively 82%, 47% and 85%. In 101 cases (44%), POCUS led to at least one
imaging change. The clinical value of POCUS, i.e. considering at least one impact
and/or imaging change, was assessed at 95%. CONCLUSION: This study shows that
POCUS is used on a minority of emergency patients. However, when used, it
significantly affects diagnostic and therapeutic practices in the emergency
setting.
PMID- 28412494
TI - Video-laryngoscopes for intubation in paediatrics: Is a better view makes
everything?
PMID- 28412495
TI - Epidemiology of Environmental Exposure and Malignant Mesothelioma.
AB - Although the association between exposure to asbestos and malignant mesothelioma
(particularly malignant pleural mesothelioma) has been well established, the
health impact of environmental exposure (EE) to asbestos has been less studied.
This review summarizes the most recent studies on the association between
malignant mesothelioma and EE with asbestos to identify features associated with
EE and quantify the association with malignant mesothelioma. There were 44
studies from 18 countries that met our selection criteria, with a considerable
amount of heterogeneity in their study design, measures of exposure, and health
outcomes. The male-to-female ratio was close to or less than 1 and generally
lower than the ratio reported when both occupational and environmental exposures
were considered. Although recent studies have continued to improve our
understanding of environmental exposure to asbestos, challenges remain. We have
highlighted a few new research directions, such as a need for reliable matrices
to identify common and less recognized types of EE, asbestos biomarker studies
specifically focusing on EE, and research on populations and geographic areas
that have not been previously studied.
PMID- 28412496
TI - Magnesium sulfate (MG) prevents maternal inflammation induced offspring cerebral
injury evident on MRI but not via IL-1beta.
AB - OBJECTIVE: As maternal treatment with magnesium sulfate (MG) may protect the
fetal brain, we sought to assess the inflammation associated neuroprotective
potential of MG and its association to interleukin 1beta (IL-1beta). METHODS:
Pregnant Sprague-Dawley rats at 18-day gestation received i.p. lipopolysaccharide
(LPS) or saline. Dams were randomized to treatment with s.c. saline (control), or
MG prior to or following the i.p. injection, resulting in three groups. At the
end of the treatment, fetal brain IL-1beta was quantified for 18 pregnant rats
(six of each group). Another 18 pregnant rats delivered spontaneously and pups
were allowed to mature. At postnatal day 25, female offspring were examined by
magnetic resonance imaging (MRI) and analyzed using voxel based analysis.
Apparent diffusion coefficient (ADC) and T2 relaxation protocols were performed
to assess white and gray matter injury. RESULTS: Offspring of LPS-treated dams
exhibited (1) significantly increased T2 levels, and (2) increased ADC levels in
white and gray matter, consistent with diffuse cerebral injury. Offspring of MG
treated LPS dams demonstrated similar T2 and ADC levels as control dams. Fetal
brain IL-1beta was significantly increased following maternal LPS compared to
control (0.125+/-0.01 vs 0.100+/-0.01u, p<0.05). No significant decrease in IL
1beta level was observed in response to maternal MG. CONCLUSIONS: Maternal LPS
induced neonatal brain injury can be prevented by maternal MG. Maternal MG
therapy may be effective in human deliveries associated with maternal/fetal
inflammation. The absence of a decrease in fetus brain levels of IL-1beta
following MG treatment implies that the mechanism of MG is not through inhibition
of IL-1beta production. SIGNIFICANCE STATEMENT: Intrauterine fetal exposure to
maternal inflammation and pro-inflammatory cytokines is associated with adverse
offspring neurological outcomes. Although its precise mechanism is not
elucidated, magnesium sulfate (MG) is commonly used as neuroprotection for white
matter brain injuries in preterm fetuses. A proposed mechanism involves the
ability of MG to reduce pro-inflammatory cytokine levels. In the current study,
we used a rat model of LPS-induced maternal inflammation to investigate the short
term effect of MG on fetal brain IL-1beta levels, and its long-term
neuroprotective effect on the offspring brain by using MRI. We demonstrated that
maternal administration of MG can prevent long-term neonatal brain injury but,
since no decrease was observed in fetal brain IL-1beta levels, the neuro
protective mechanism of MG is not mediated by inhibition of IL-1beta production.
PMID- 28412498
TI - Impact of thalamocortical input on barrel cortex development.
AB - The development of cortical maps requires the balanced interaction between
genetically determined programs and input/activity-dependent signals generated
spontaneously or triggered from the environment. The somatosensory pathway of
mice provides an excellent scenario to study cortical map development because of
its highly organized cytoarchitecture, known as the barrel field. This precise
organization makes evident even small alterations in the cortical map layout. In
this review, we will specially focus on the thalamic factors that control barrel
field development. We will summarize the role of thalamic input integration and
identity, neurotransmission and spontaneous activity in cortical map formation
and early cross-modal plasticity.
PMID- 28412497
TI - Optogenetic stimulation of cortex to map evoked whisker movements in awake head
restrained mice.
AB - Whisker movements are used by rodents to touch objects in order to extract
spatial and textural tactile information about their immediate surroundings. To
understand the mechanisms of such active sensorimotor processing it is important
to investigate whisker motor control. The activity of neurons in the neocortex
affects whisker movements, but many aspects of the organization of cortical
whisker motor control remain unknown. Here, we filmed whisker movements evoked by
sequential optogenetic stimulation of different locations across the left dorsal
sensorimotor cortex of awake head-restrained mice. Whisker movements were evoked
by optogenetic stimulation of many regions in the dorsal sensorimotor cortex.
Optogenetic stimulation of whisker sensory barrel cortex evoked retraction of the
contralateral whisker after a short latency, and a delayed rhythmic protraction
of the ipsilateral whisker. Optogenetic stimulation of frontal cortex evoked
rhythmic bilateral whisker protraction with a longer latency compared to
stimulation of sensory cortex. Compared to frontal cortex stimulation, larger
amplitude bilateral rhythmic whisking in a less protracted position was evoked at
a similar latency by stimulating a cortical region posterior to Bregma and close
to the midline. These data suggest that whisker motor control might be broadly
distributed across the dorsal mouse sensorimotor cortex. Future experiments must
investigate the complex neuronal circuits connecting specific cell-types in
various cortical regions with the whisker motor neurons located in the facial
nucleus.
PMID- 28412499
TI - Parkinsonism and dystonia are differentially induced by modulation of different
territories in the basal ganglia.
AB - Numerous clinical and experimental observations suggest that deficient neuronal
signaling in the globus pallidus externa (GPe) is integral to both Parkinson's
disease (PD) and dystonia. In our previous studies in jaundiced dystonic rats,
widespread silencing of neurons in GP (rodent equivalent to GPe) preceded and
persisted during dystonic motor activity. We therefore hypothesized that on a
background of slow and highly irregular and bursty neuronal activity in GP,
cortical motor drive produces profound inhibition of GP as the basis for action
induced dystonia in Gunn rats. Presently, the neurotoxin ibotenate was injected
locally into the motor territory of GP at one to four sites, over one to two
tracts, in 19 normal rats. We found that highly circumscribed dorsal motor
territory lesions reproducibly induced parkinsonism, while ventral lesions
consistently produced dystonia. Post-lesioning, slow neuronal burst oscillations
in the entopeduncular nucleus distinguished parkinsonian from dystonic rats.
Next, we compared the deep brain stimulation contact sites in the GP internus
used to treat patients with PD (n=21 implants in 12 successive patients) versus
dystonia (n=16 implants in nine patients) and found the efficacious territory for
ameliorating PD to be located chiefly dorsal to that for dystonia. The
comparative distribution for treating PD versus dystonia was therefore
anatomically consistent with that for inducing these features via GP lesions in
rodents. Our collective findings thus suggest that dystonia and parkinsonism are
differentially produced by pathological silencing of GPe neurons along distinct
motor sub-circuits, resulting in disparate pathological basal ganglia output
signaling.
PMID- 28412500
TI - The major neurotransmitter systems in the basolateral amygdala and the ventral
tegmental area mediate morphine-induced memory consolidation impairment.
AB - In the present study, we investigated the possible participation of the
endocannabinoid system in the basolateral amygdala and N-methyl-d-aspartate
(NMDA) or GABA-A receptor neurotransmission in the ventral tegmental area in the
memory consolidation impairment induced by morphine administration. To measure
memory formation, step-through type passive avoidance apparatus was used with
adult male Wistar rats. The results showed that intraperitoneal (i.p.)
administration of morphine (3 and 6mg/kg) after the successful training phase had
an amnestic effect and induced memory consolidation impairment. After training,
injection of a selective cannabinoid CB1 receptor agonist,
arachydonilcyclopropylamide (ACPA; 0.4-0.6ng/rat) plus systemic injection of an
ineffective dose of morphine (0.5mg/kg, i.p.) into the basolateral amygdala
impaired memory consolidation suggesting the facilitatory effect of ACPA on
morphine response. Also, the results showed that the injection of bicuculline, a
GABA-A receptor antagonist (0.3-0.5ug/rat) or NMDA (0.005-0.02ug/rat) into the
ventral tegmental area reversed ACPA-induced potentiation of morphine response
and improved memory consolidation. It should be considered that the injection of
ACPA into the basolateral amygdala and the injection of bicuculline or NMDA into
the ventral tegmental area alone could not affect memory consolidation. Taken
together, it seems that there is a functional interaction between the basolateral
amygdala endocannabinoid system and the ventral tegmental area GABAergic- or
glutamatergic neurotransmission in the modulation of morphine-induced memory
consolidation impairment.
PMID- 28412501
TI - Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in
response to cocaine.
AB - Chromatin regulation, in particular ATP-dependent chromatin remodelers, have
previously been shown to be important in the regulation of reward-related
behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A,
an accessory subunit of the ISWI family of chromatin remodeling complexes, is
downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to
cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in
mouse NAc reduces cocaine reward as assessed by conditioned place preference
(CPP), but increases cocaine-induced locomotor activation. Furthermore, we
investigate nucleosome repositioning genome-wide by conducting chromatin
immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and
after repeated cocaine administration, and find extensive nucleosome occupancy
and shift changes across the genome in response to cocaine exposure. These
findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and
offer new insight into the pathophysiology of cocaine addiction.
PMID- 28412502
TI - Enriched environment effects on remote object recognition memory.
AB - Since Ebbinghaus' classical work on oblivion and saving effects, we know that
declarative memories may become at first spontaneously irretrievable and only
subsequently completely extinguished. Recently, this time-dependent path toward
memory-trace loss has been shown to correlate with different patterns of brain
activation. Environmental enrichment (EE) enhances learning and memory and
affects system memory consolidation. However, there is no evidence on whether and
how EE could affect the time-dependent path toward oblivion. We used Object
Recognition Test (ORT) to assess in adult mice put in EE for 40days (EE mice) or
left in standard condition (SC mice) memory retrieval of the familiar objects 9
and 21days after learning with or without a brief retraining performed the day
before. We found that SC mice show preferential exploration of new object at day
9 only with retraining, while EE mice do it even without. At day 21 SC mice do
not show preferential exploration of novel object, irrespective of the
retraining, while EE mice are still capable to benefit from retraining, even if
they were not able to spontaneously recover the trace. Analysis of c-fos
expression 20days after learning shows a different pattern of active brain areas
in response to the retraining session in EE and SC mice, with SC mice recruiting
the same brain network as naive SC or EE mice following de novo learning. This
suggests that EE promotes formation of longer lasting object recognition memory,
allowing a longer time window during which saving is present.
PMID- 28412503
TI - Internet search volumes in brain aneurysms and subarachnoid hemorrhage: Is there
evidence of seasonality?
AB - OBJECTIVE: Results of previous studies examining seasonal variation in the
incidence of aneurysmal subarachnoid hemorrhage (SAH) are conflicting. The aim of
this brief report is to investigate whether there is a seasonal effect in online
search queries for SAH that may reflect an association between meteorological
factors and aneurysm rupture. PATIENTS AND METHODS: We used the Google Trends
data service to analyze the volume of internet queries for SAH on Google's search
engine from January 1, 2004 to November 2016. We used comprehensive search terms
and collected data from: USA, Canada, and countries known for their high
prevalence of SAH (Finland, and Japan), as well as worldwide search volume.
Potential seasonal variations in the data were assessed by comparative non
parametric tests and curve-fit regression model. RESULTS: Our analyses revealed
that USA had the highest median value in cumulative search scores (115 vs. 86,
46, 46 for Finland, Canada and Japan, respectively). The term "brain aneurysm"
was the commonly used search term among countries, followed by "cerebral
aneurysm". There was no evidence of seasonality in any of the countries studied
on both univariate tests and regression time-adjusted analysis. CONCLUSIONS:
There are no seasonal variations in internet search query volume for SAH. Further
studies are needed to explore whether online search volumes correlate with the
actual incidence of SAH.
PMID- 28412504
TI - Endotoxin induced TLR4 signaling downregulates CYP19A1 expression through CEBPB
in buffalo granulosa cells.
AB - Estrogen is essential for growth and development of ovarian follicles. Infections
associated with E. coli or Endotoxin (LPS) suppress estradiol production by the
downregulation of CYP19A1 expression. However, the molecular mechanism of its
down regulation is not yet known. To elucidate the molecular mechanisms of LPS
mediated downregulation of CYP19A1 gene expression, we studied the effect of LPS
and TLR4 signaling pathway inhibitor (OxPAPC, OxPAPC-Oxidized 1-palmitoyl-2
arachidonoyl-sn-glycero-3-phosphocholine) on CYP19A1 expression, and expression
of CEBPB and CEBPB binding on CYP19A1 proximal promoter (CYP19A1 PII) in buffalo
granulosa cells in vitro. The results showed that LPS (1MUg/ml) significantly
declined the expression of CYP19A1 gene. In further experiments, inhibitor
studies confirmed the involvement of TLR4 in LPS induced CYP19A1 gene down
regulation in buffalo granulosa cells. LPS promoted higher levels of CEBPB at
cellular and nuclear level in granulosa cells. Chromatin immunoprecipitation
results showed, that LPS induces higher amount of CEBPB binding on the CYP19A1
PII. Further, TLR4 inhibitor attenuated the LPS induced implications. In
conclusion, our results demonstrated that CEBPB could be a potential regulator
for LPS mediated downregulation of CYP19A1 and decline of 17-beta estradiol
levels in buffalo granulosa cells.
PMID- 28412505
TI - Various UVB doses affect change of raf kinase inhibitor protein, nitric oxide and
proliferation in keratinocytes.
AB - UVB is a potent modulator of cell growth and differentiation in the skin. The UVB
irradiation has been used in treating hyperproliferative dermatoses. Otherwise,
UVB radiation is also the major risk factor for developing skin cancer. Nitric
oxide (NO) has been suggested to be a physiological modulator of cell
proliferation. Raf-1 kinase inhibitory protein (RKIP) was involved in cell
growth, transformation, and differentiation. The purpose of this study was to
search for the possible cause of UVB-inhibited hyperplasia and UVB-resulted
hyperproliferation. We evaluated various UVB dose whether affect the expression
of RKIP, iNOS, NO and proliferation in keratinocyte. Normal human keratinocytes
were treated with UVB dose of 40mJ/cm2, 80mJ/cm2, 120mJ/cm2, 160mJ/cm2 and
0mJ/cm2 (control group) respectively. The results showed that RKIP, iNOS and NO
of keratinocytes with doses of 40mJ/cm2 and 80mJ/cm2 UVB treatment significantly
higher than control group (P<0.01). The proliferation of keratinocyte with doses
of 40mJ/cm2 and 80mJ/cm2 UVB treatment was significantly lower than control group
(P<0.01). However, RKIP, iNOS and NO of keratinocytes with doses of 120mJ/cm2 and
160mJ/cm2 UVB treatment significantly lower than control group (P<0.01). The
proliferation of keratinocyte with doses of 120mJ/cm2 and 160mJ/cm2 UVB treatment
was significantly higher than control group (P<0.01). In conclusion, these
results showed that the different UVB dosages induced various alteration of RKIP,
NO, iNOS and proliferation may provide important information on the therapeutic
molecular mechanism of UVB-inhibited hyperplasia and UVB resulted
hyperproliferation.
PMID- 28412506
TI - Long-term di (2-ethylhexyl)-phthalate exposure promotes proliferation and
survival of HepG2 cells via activation of NFkappaB.
AB - Di (2-ethylhexyl)-phthalate (DEHP) is the most commonly used plasticizer. DEHP
can easily leach out from products into the environment and has become a
significant environmental contamination. However, its carcinogenic effects in
human remain controversial. In this study, we exposed hepatocellular carcinoma
HepG2 cells to different concentrations of DEHP for a period of times, followed
by a combination of RNA-seq analysis and molecular analysis for DEHP-altered
genes. We observed that long-term and very low-dose DEHP treatment has growth
inducing activity in HepG2 cells, while short-term and high-dose DEHP treatment
has little effects on tumor cell proliferation. Bioinformatic analysis further
revealed that a large subset of differentially expressed genes affected by DEHP
have functional annotations related to inflammation response. Importantly we
found that long-term DEHP treatment stimulated nuclear factor-kappa B (NF-kappa
B) activity in HepG2 cells, while inhibition of NFkappaB activity could offset
the effects of DEHP exposure. In conclusion, continuous DEHP treatment could
promote proliferation of HepG2 cells via activating NFkappaB signaling pathway.
PMID- 28412507
TI - Transcriptomic analyses of human bronchial epithelial cells BEAS-2B exposed to
atmospheric fine particulate matter PM2.5.
AB - Respiratory exposure is the major route of atmospheric PM2.5 entering the human
body. Epidemiological studies have indicated that exposure to PM2.5 is associated
with increased risk of pulmonary diseases, but the underlying mechanisms remain
less clear. In this study, human bronchial epithelial cells (BEAS-2B) were used
to investigate the toxic effect and gene expression changes induced by PM2.5
collected from Beijing, China, based on microarray and following bioinformatic
analyses. Gene ontology (GO) analysis indicated that PM2.5 caused significant
changes in gene expression patterns related to a series of important functions,
covering gene transcription, signal transduction, cell proliferation, cellular
metabolic processes, immune response, etc. Additionally, pathway analysis and
signal-net analysis showed that PI3K/Akt, MAPK, and TNF signaling pathways were
the most prominently significant pathways affected by PM2.5, which play key roles
in regulating cell proliferation, cell differentiation, cytoskeleton regulation,
and inflammatory response. Finally, for the purpose of verifing the accuracy of
microarray analysis, qRT-PCR was used to detect the expression of part key genes
in the above signaling pathways, which were selected from the signal-net. Our
study provided a large amount of information on the molecular mechanism that
underling PM2.5 caused pulmonary diseases, and follow-up researches are still
needed for further exploration.
PMID- 28412508
TI - Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24), a novel
tubulin inhibitor, causes G2/M arrest and cell apoptosis by disrupting tubulin
polymerization in human cervical and breast cancer cells.
AB - Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24) is a
newly synthesized analogue of nocodazole by our group and has been found to be
active for some cancer cells. However, its sensitivity to different cell lines
and the underlying anticancer mechanism are still unclear. In this study, we
proved that M-24 had strong time- and dose-dependent anti-proliferative effects
on human cervical cancer HeLa cells and human breast carcinoma MCF-7 cells. We
demonstrated that the growth inhibitory effects of M-24 in both cell lines were
associated with microtubule depolymerization. Furthermore, M-24 treatment
resulted in cell cycle arrest at the G2/M phase in a dose-dependent manner with
subsequent apoptosis induction. Western blotting analysis revealed that up
regulation of cyclin B1 and cdc2 was related with G2/M arrest in both cell lines.
In addition, M-24-induced HeLa cell apoptosis was mainly associated with
mitochondria-dependent intrinsic pathway. However, M-24-induced MCF-7 cell
apoptosis was associated with both mitochondrial and death receptor pathway. In
conclusion, M-24 caused apoptosis through disrupting microtubule assembly and
inducing cell cycle arrest in HeLa and MCF-7 cells. Therefore, the novel compound
M-24 is a promising microtubule-destabilizing agent that has great potential for
the therapy of various malignancies especially human cervical and breast cancers.
PMID- 28412509
TI - A monoclonal antibody recognizes undifferentiation-specific carbohydrate moieties
expressed on cell surface of the human dental pulp cells.
AB - Human dental pulp cells are obtained from dental pulp tissue, and have the
ability to form dentin and a pulp-like complex. Although adult stem cells have
been identified from the primary culture by using specific cell surface markers,
the identity of surface markers for the purification of stem cells within the
dental pulp population are still unclear. Previously, we had constructed
monoclonal antibodies against the undifferentiated cell-specific surface markers
of human dental pulp cells (hDPCs) by performing decoy immunization. Among them,
a monoclonal antibody against the cell surface antigen of the undifferentiated
hDPCs (named UPSA-1) was purified and its heavy and light chain consensus regions
were analyzed. The cell surface binding affinity of UPSA-1 mAb on the
undifferentiated hDPCs was stronger than that on the differentiated cells. When
tunicamycin was applied to hDPSCs during culture, the cell surface binding
affinity of the antibody was dramatically decreased, and dentinogenic
differentiation was reduced. The purified UPSA-1 antigen band resulting from
immunoprecipitation disappeared or shifted down on the SDS-PAGE by
deglycosylation. These data suggested that glycosylation on the cell surface
might be a marker of an undifferentiated state, and that UPSA-1 mAb might be
useful for identifying the carbohydrate moiety on the cell surface of
undifferentiated pulp cells.
PMID- 28412510
TI - Empathy networks in the parental brain and their long-term effects on children's
stress reactivity and behavior adaptation.
AB - Parental empathy is a key component of sensitive parenting that supports
children's social adaptation throughout life. Consistent with a two dissociable
network perspective on empathy, we measured within- and between-network integrity
of two empathy-related networks in the parental brain as predictors of children's
social outcomes across the first six years of life. We focused on two empathy
networks; embodied simulation, which supports parents' capacity to resonate with
infant state and emotions and implicates cingulo-insulary structures, and
mentalizing, which underpins parents' theory-of-mind and mental attributions via
prefrontal-temporo-parietal circuit. We followed 87 first-time parents across the
first six years of family formation, including heterosexual and homosexual
parents. In infancy, parents' brain response to own versus unfamiliar infant
stimuli was imaged; in preschool, children's cortisol production and emotion
regulation were assessed; and at six years, children's behavior problems were
reported. Parents' intra- and inter- network integrity increased when viewing
their own infant compared to unfamiliar infant, suggesting that attachment
stimuli increase network coherence in the parental brain. Functional connectivity
within the parent's embodied simulation network in infancy predicted lower child
cortisol production while inter-network connectivity among the embodied
simulation and mentalizing networks was associated with more advanced child
emotion regulation skills in preschool and lower internalizing problems at six
years. Children's emotion regulation capacities mediated the link between inter
network integrity in the parental brain and internalizing symptoms. Our findings,
the first to demonstrate that integrity of empathy-related networks in the
parental brain shape children's long-term stress reactivity and emotional
adaptation, highlight the brain component of the parental empathy attribute,
suggest that increased coherence within the "parental caregiving network" marks a
key feature of parent-infant attachment, and contribute to discussion on
biobehavioral mechanisms underpinning the cross-generation transmission of human
stress reactivity and sociality.
PMID- 28412511
TI - Difference in neural response to social exclusion observation and subsequent
altruism between adolescents and adults.
AB - Empathy and prosocial behaviors toward peers promote successful social
development and creation of significant long-term relationships, but surprisingly
little is known about the maturation of these skills during the period of
adolescence. As the majority of studies have used questionnaires or pain
observation paradigms, it remains unknown whether the empathic response of
adolescents differs from that of adults in a paradigm that is closer to everyday
life. In the current study, fMRI was used to examine the neural correlates of
social exclusion observation and subsequent prosocial behavior in 20 adolescents
(aged 12-17 years) and 20 adults (aged 22-30 years) while playing a ball-tossing
game with what they believed to be real individuals. Observing someone being
excluded compared to observing equal inclusion of all players elicited a
significantly higher activation of the IFG (pars triangularis) in adults compared
to adolescents. When given the opportunity to directly help the excluded player
during the game, adolescents showed significantly less prosocial behavior than
adults, which was underpinned by a significantly lower activity in the right
temporoparietal junction, medial/dorsomedial prefrontal cortex and fusiform face
area. These findings might indicate that adolescents have a lower propensity to
take the victim's perspective and share his or her distress when witnessing
social exclusion, which leads to a lower altruistic motivation to help. The
factors that could generate what can be interpreted as a downward modulation of
empathy during adolescence are discussed.
PMID- 28412513
TI - Wolbachia-induced loss of male fertility is likely related to branch chain amino
acid biosynthesis and iLvE in Laodelphax striatellus.
AB - Wolbachia are endosymbionts that infect many species of arthropods and nematodes.
Wolbachia-induced cytoplasmic incompatibility (CI) is the most common phenotype
in affected hosts, involving embryonic lethality in crosses between Wolbachia
infected males and uninfected females. The molecular mechanisms underlying this
phenomenon are currently unclear. Here we examine the molecular correlates of the
Wolbachia infection in Laodelphax striatellus (Fallen), an important rice pest,
where embryonic lethality is strong and almost complete. We compared the gene
expression of 4-day-old Wolbachia-infected and uninfected L. striatellus testes
to identify candidate genes for paternal-effect embryonic lethality induction.
Based on microarray analysis, iLvE was the most down-regulated gene; this gene
mediates branched-chain amino acid (BCAA) biosynthesis and participates in many
processes related to reproductive performance. After knocking down iLvE by RNAi
in uninfected male L. striatellus, male fertility was reduced, leading to a
decrease in embryo hatching rates, but fertility was rescued in crosses between
these males and Wolbachia-infected females. Removal of BCAA in chemically-defined
diets of uninfected males also led to a loss of male fertility. Low amino acid
nutrition may enhance exposure time of sperm to Wolbachia in the testes to affect
adult reproduction in L. striatellus by reducing the number of sperm transferred
per mating by males. These results indicate that Wolbachia may decrease male
fertility in L. striatellus by acting on iLvE, a key factor of BCAA biosynthesis,
and delaying sperm maturation.
PMID- 28412512
TI - Addressing the selective role of distinct prefrontal areas in response
suppression: A study with brain tumor patients.
AB - The diverging evidence for functional localization of response inhibition within
the prefrontal cortex might be justified by the still unclear involvement of
other intrinsically related cognitive processes like response selection and
sustained attention. In this study, the main aim was to understand whether
inhibitory impairments, previously found in patients with both left and right
frontal lesions, could be better accounted for by assessing these potentially
related cognitive processes. We tested 37 brain tumor patients with left
prefrontal, right prefrontal and non-prefrontal lesions and a healthy control
group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory
impairments are likely to cause false alarms, although additionally the former
task requires response selection and the latter target detection abilities.
Irrespective of the task context, patients with right prefrontal damage showed
frequent Go and target omissions, probably due to sustained attention lapses.
Left prefrontal patients, on the other hand, showed both Go and target omissions
and high false alarm rates to No-Go and warning stimuli, suggesting a decisional
rather than an inhibitory impairment. An exploratory whole-brain voxel-based
lesion-symptom mapping analysis confirmed the association of left ventrolateral
and dorsolateral prefrontal lesions with target discrimination failure, and right
ventrolateral and medial prefrontal lesions with target detection failure.
Results from this study show how left and right prefrontal areas, which previous
research has linked to response inhibition, underlie broader cognitive control
processes, particularly involved in response selection and target detection.
Based on these findings, we suggest that successful inhibitory control relies on
more than one functionally distinct process which, if assessed appropriately,
might help us to better understand inhibitory impairments across different
pathologies.
PMID- 28412514
TI - Insights from the genome of a high alkaline cellulase producing Aspergillus
fumigatus strain obtained from Peruvian Amazon rainforest.
AB - Here, we report the complete genome sequence of a high alkaline cellulase
producing Aspergillus fumigatus strain LMB-35Aa isolated from soil of Peruvian
Amazon rainforest. The genome is ~27.5mb in size, comprises of 228 scaffolds with
an average GC content of 50%, and is predicted to contain a total of 8660 protein
coding genes. Of which, 6156 are with known function; it codes for 607 putative
CAZymes families potentially involved in carbohydrate metabolism. Several
important cellulose degrading genes, such as endoglucanase A, endoglucanase B,
endoglucanase D and beta-glucosidase, are also identified. The genome of A.
fumigatus strain LMB-35Aa represents the first whole sequenced genome of non
clinical, high cellulase producing A. fumigatus strain isolated from forest soil.
PMID- 28412515
TI - Genome-wide determination of transcription start sites reveals new insights into
promoter structures in the actinomycete Corynebacterium glutamicum.
AB - The genome-wide identification of transcription start sites, enabled by high
throughput sequencing of a cDNA library enriched for native 5' transcript ends,
is ideally suited for the analysis of promoters. Here, the transcriptome of
Corynebacterium glutamicum, a non-pathogenic soil bacterium from the
actinomycetes branch that is used in industry for the production of amino acids,
was analysed by transcriptome sequencing of the 5'-ends of native transcripts.
Total RNA samples were harvested from the exponential phase of growth, therefore
the study mainly addressed promoters recognized by the main house-keeping sigma
factor sigmaA. The identification of 2454 transcription start sites (TSS) allowed
the detailed analysis of most promoters recognized by sigmaA and furthermore
enabled us to form different promoter groups according to their location relative
to protein-coding regions. These groups included leaderless transcripts (546
promoters), short-leadered (<500 bases) transcripts (917), and long-leadered
(>500 bases) transcripts (173) as well as intragenic (557) and antisense
transcripts (261). All promoters and the individual groups were searched for
information, e.g. conserved residues and promoter motifs, and general design
features as well as group-specific preferences were identified. A purine was
found highly favored as TSS, whereas the -1 position was dominated by
pyrimidines. The spacer between TSS and -10 region were consistently 6-7 bases
and the -10 promoter motif was generally visible, whereas a recognizable -35
region was only occurring in a smaller fraction of promoters (7.5%) and enriched
for leadered and antisense transcripts but depleted for leaderless transcripts.
Promoters showing an extended -10 region were especially frequent in case of non
canonical -10 motifs (45.5%). Two bases downstream of the -10 core region, a G
was conserved, exceeding 40% abundance in most groups. This fraction reached
74.6% for a group of putative sigmaB-dependent promoters, thus giving a hint to a
specific property of these promoters. In addition, the high number of promoters
analysed allowed finding of subtle signals only showing up significantly with
this large set. This included the observation of a periodically changing A+T
content with maxima spaced by a full turn of the DNA helix. This periodic
structure includes the A+T-rich UP-element of bacterial promoters known before
but was found to extend up to -100, indicating hitherto unknown constraints
influencing promoter architecture and possibly also promoter function.
PMID- 28412516
TI - Switching between nitrogen and glucose limitation: Unraveling transcriptional
dynamics in Escherichia coli.
AB - Transcriptional control under nitrogen and carbon-limitation conditions have been
well analyzed for Escherichia coli. However, the transcriptional dynamics that
underlie the shift in regulatory programs from nitrogen to carbon limitation is
not well studied. In the present study, cells were cultivated at steady state
under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose)
limitation to monitor changes in transcriptional dynamics. Nitrogen limitation
was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the
"housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under
glucose limitation. During the transition, nitrogen-mediated control was rapidly
redeemed and mRNAs that encode active uptake systems, such as ptsG and manXYZ,
were quickly amplified. Next, genes encoding facilitators such as lamB were
overexpressed, followed by high affinity uptake systems such as mglABC and non
specific porins such as ompF. These regulatory programs are complex and require
well-equilibrated and superior control. At the metabolome level, 2-oxoglutarate
is the likely component that links carbon- and nitrogen-mediated regulation by
interacting with major regulatory elements. In the case of dual glucose and
ammonia limitation, sigma 24 (RpoE) appears to play a key role in orchestrating
these complex regulatory networks.
PMID- 28412517
TI - Challenges around Access to and Cost of Life-Saving Medications after Allogeneic
Hematopoietic Cell Transplantation for Medicare Patients.
AB - Hematopoietic cell transplantation (HCT) is an expensive, medically complicated,
and potentially life-threatening therapy for multiple hematologic and
nonhematologic disorders with a prolonged trajectory of recovery. Similar to
financial issues in other cancer treatments, adverse financial consequences of
HCT are emerging as an important issue and may be associated with poor quality of
life and increased distress in HCT survivors. Prescription medicine coverage for
HCT for Medicare and some Medicaid beneficiaries, especially in the long-term,
remains suboptimal because of inadequate payer formularies or prohibitive copays.
With an increasing number of older patients undergoing HCT and improvement in the
overall survival after HCT, the problem of financial burden faced by Medicare
beneficiaries with fixed incomes is going to worsen. In this article, we describe
the typical financial burden borne by HCT recipients based on estimated copayment
amounts attached to the categories of key medications as elucidated through 2
case studies. We also suggest some possible solutions for consideration to help
these patients and families get through the HCT by minimizing the financial
burden from essential medications needed during the post-HCT period.
PMID- 28412519
TI - Vitamin D signaling in intestinal innate immunity and homeostasis.
AB - The lumen of the gut hosts a plethora of microorganisms that participate in food
assimilation, inactivation of harmful particles and in vitamin synthesis. On the
other hand, enteric flora, a number of food antigens, and toxins are capable of
triggering immune responses causing inflammation, which, when unresolved, may
lead to chronic conditions such as inflammatory bowel disease (IBD). It is
important, therefore, to contain the gut bacteria within the lumen, control
microbial load and composition, as well as ensure adequate innate and adaptive
immune responses to pathogenic threats. There is growing evidence that vitamin D
signaling has impacts on all these aspects of intestinal physiology, contributing
to healthy enteric homeostasis. VD was first discovered as the curative agent for
nutritional rickets, and its classical actions are associated with calcium
absorption and bone health. However, vitamin D exhibits a number of extra
skeletal effects, particularly in innate immunity. Notably, it stimulates
production of pattern recognition receptors, anti-microbial peptides, and
cytokines, which are at the forefront of innate immune responses. They play a
role in sensing the microbiota, in preventing excessive bacterial overgrowth, and
complement the actions of vitamin D signaling in enhancing intestinal barrier
function. Vitamin D also favours tolerogenic rather than inflammogenic T cell
differentiation and function. Compromised innate immune function and overactive
adaptive immunity, as well as defective intestinal barrier function, have been
associated with IBD. Importantly, observational and intervention studies support
a beneficial role of vitamin D supplementation in patients with Crohn's disease,
a form of IBD. This review summarizes the effects of vitamin D signaling on
barrier integrity and innate and adaptive immunity in the gut, as well as on
microbial load and composition. Collectively, studies to date reveal that vitamin
D signaling has widespread effects on gut homeostasis, and provide a mechanistic
basis for potential therapeutic benefit of vitamin D supplementation in IBD.
PMID- 28412518
TI - Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease
Prophylaxis after Allogeneic Transplantation.
AB - Atorvastatin administration to both the donors and recipients of matched related
donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute
graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and
effective. However, its efficacy as acute GVHD prophylaxis when given only to
allo-HCT recipients is unknown. We conducted a phase II study to evaluate the
safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to
the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo
HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered
along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate.
All patients were evaluable for acute GVHD. The cumulative incidences of grade II
to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence
interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The
cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and
MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%),
respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year
were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively.
In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression
free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95%
CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to
83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95%
CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%),
and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities
attributable to atorvastatin were seen. In conclusion, the addition of
atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD
allo-HCT appears to be feasible and safe. The preliminary efficacy seen here
warrants confirmation in randomized trials.
PMID- 28412520
TI - Nutrition modulation of human aging: The calorie restriction paradigm.
AB - Globally, the aging population is growing rapidly, creating an urgent need to
attenuate age-related health conditions, including metabolic disease and
disability. A promising strategy for healthy aging based on consistently positive
results from studies with a variety of species, including non-human primates
(NHP), is calorie restriction (CR), or the restriction of energy intake while
maintaining intake of essential nutrients. The burgeoning evidence for this
approach in humans is reviewed and the major study to date to address this
question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing
Intake of Energy), is described. CALERIE findings indicate the feasibility of CR
in non-obese humans, confirm observations in NHP, and are consistent with
improvements in disease risk reduction and potential anti-aging effects. Finally,
the mechanisms of CR in humans are reviewed which sums up the fact that
evolutionarily conserved mechanisms mediate the anti-aging effects of CR.
Overall, the prospect for further research in both NHP and humans is highly
encouraging.
PMID- 28412521
TI - A lamprey view on the origins of neuroendocrine regulation of the thyroid axis.
AB - This mini review summarizes the current knowledge of the hypothalamic-pituitary
thyroid (HPT) endocrine system in lampreys, jawless vertebrates. Lampreys and
hagfish are the only two extant members of the class of agnathans, the oldest
lineage of vertebrates. The high conservation of the hypothalamic-pituitary
gonadal (HPG) axis in lampreys makes the lamprey model highly appropriate for
comparative and evolutionary analyses. However, there are still many unknown
questions concerning the hypothalamic-pituitary (HP) axis in its regulation of
thyroid activities in lampreys. As an example, the hypothalamic and pituitary
hormone(s) that regulate the HPT axis have not been confirmed and/or
characterized. Similar to gnathostomes (jawed vertebrates), lampreys produce
thyroxine (T4) and triiodothyronine (T3) from thyroid follicles that are
suggested to be involved in larval development, metamorphosis, and reproduction.
The existing data provide evidence of a primitive, overlapping yet functional HPG
and HPT endocrine system in lamprey. We hypothesize that lampreys are in an
evolutionary intermediate stage of hypothalamic-pituitary development, leading to
the emergence of the highly specialized HPG and HPT endocrine axes in jawed
vertebrates. Study of the ancient lineage of jawless vertebrates, the agnathans,
is key to understanding the origins of the neuroendocrine system in vertebrates.
PMID- 28412522
TI - Small non coding RNAs in adipocyte biology and obesity.
AB - Obesity has reached epidemic proportions world-wide and constitutes a substantial
risk factor for hypertension, type 2 diabetes, cardiovascular diseases and
certain cancers. So far, regulation of energy intake by dietary and
pharmacological treatments has met limited success. The main interest of current
research is focused on understanding the role of different pathways involved in
adipose tissue function and modulation of its mass. Whole-genome sequencing
studies revealed that the majority of the human genome is transcribed, with
thousands of non-protein-coding RNAs (ncRNA), which comprise small and long
ncRNAs. ncRNAs regulate gene expression at the transcriptional and post
transcriptional level. Numerous studies described the involvement of ncRNAs in
the pathogenesis of many diseases including obesity and associated metabolic
disorders. ncRNAs represent potential diagnostic biomarkers and promising
therapeutic targets. In this review, we focused on small ncRNAs involved in the
formation and function of adipocytes and obesity.
PMID- 28412523
TI - Progenitor strain introduction of Mycobacterium bovis at the wildlife-livestock
interface can lead to clonal expansion of the disease in a single ecosystem.
AB - Mycobacterium bovis infects multiple wildlife species and domesticated cattle
across South Africa, and negatively impacts on livestock trade and movement of
wildlife for conservation purposes. M. bovis infection was first reported in the
Kruger National Park (KNP) in South Africa during the 1990s, and has since spread
to infect numerous animal host species throughout the park and across South
Africa. Whole genome sequencing data of 17 M. bovis isolates were analyzed to
investigate the genomic diversity among M. bovis isolates causing disease in
different animal host species from various locations in South Africa. M. bovis
strains analyzed in this study are geographic rather than host species-specific.
The clonal expansion of M. bovis in the KNP highlights the effect of an
introduction of a transmissible infectious disease leading to a rising epidemic
in wildlife, and emphasizes the importance of disease control and movement
restriction of species that serve as disease reservoirs. In conclusion, the point
source introduction of a single M. bovis strain type in the KNP ecosystem lead to
an M. bovis outbreak in this area that affects various host species and poses an
infection risk in neighboring rural communities where HIV prevalence is high.
PMID- 28412524
TI - Antimicrobial resistance and genetic diversity of the SXT element in Vibrio
cholerae from clinical and environmental water samples in northeastern Thailand.
AB - Multidrug resistance in V. cholerae has been increasing around the world
including northeastern Thailand. The aquatic environment is a reservoir of V.
cholerae and might be an important source of resistant strains. The aims of this
study were to investigate the phylogenetic relationships of intSXT gene sequences
from 31 clinical and 14 environmental V. cholerae O1 and non-O1/non-O139 isolates
and 11 sequences amplified directly from environmental water samples. We also
amplified class 1 integrons, the SXT elements (targeting the intSXT gene) and
antimicrobial resistance genes directly from water samples. Phylogenetic analysis
displayed two major distinct clusters (clusters 1 and 2). Most V. cholerae O1
(19/20, 95%) and non-O1/non-O139 isolates (8/11, 72.7%) from clinical sources,
and all sequences obtained directly from water samples, belonged to cluster 1.
Cluster 2 mostly comprised environmental non-O1/non-O139 isolates (10/12, 83.3%).
We successfully amplified the SXT elements directly from17.5% of water samples.
Associated resistance genes were also amplified as follows: sul2 (41.3% of water
samples), dfrA1 (60%), dfr18 (33.8%), strB (70%) and tetA (2.5%). Class 1
integrons were not found in water samples, indicating that the SXT element was
the major contributor of multidrug resistance determinants in this region. The
SXT element and antimicrobial resistance genes could be transferred from clinical
V. cholerae O1 to environmental V. cholerae non-O1/non-O139 was demonstrated by
conjugation experiment. These findings indicate that there may have been cross
dissemination and horizontal gene transfer (HGT) of the SXT element harbored by
V. cholerae O1 and non-O1/non-O139 strains isolated from clinical and
environmental water sources. Environmental water might be an important source of
antimicrobial resistance genes in V. cholerae in this region. Direct detection of
antimicrobial resistance genes in water samples can be used for monitoring the
spread of such genes in the ecosystem.
PMID- 28412525
TI - Liver microbiome of Peromyscus leucopus, a key reservoir host species for
emerging infectious diseases in North America.
AB - Microbiome studies generally focus on the gut microbiome, which is composed of a
large proportion of commensal bacteria. Here we propose a first analysis of the
liver microbiome using next generation sequencing as a tool to detect potentially
pathogenic strains. We used Peromyscus leucopus, the main reservoir host species
of Lyme disease in eastern North America, as a model and sequenced V5-V6 regions
of the 16S gene from 18 populations in southern Quebec (Canada). The
Lactobacillus genus was found to dominate the liver microbiome. We also detected
a large proportion of individuals infected by Bartonella vinsonii arupensis, a
human pathogenic bacteria responsible for endocarditis, as well as Borrelia
burgdorferi, the pathogen responsible for Lyme disease in North America. We then
compared the microbiomes among two P. leucopus genetic clusters occurring on
either side of the St. Lawrence River, and did not detect any effect of the host
genotype on their liver microbiome assemblage. Finally, we report, for the first
time, the presence of B. burgdorferi in a small mammal host from the northern
side of the St. Lawrence River, in support of models that have predicted the
northern spread of Lyme disease in Canada.
PMID- 28412526
TI - Birth setting, labour experience, and postpartum psychological distress.
AB - OBJECTIVE: although psychosocial risk factors have been identified for postpartum
depression (PPD) and perinatal posttraumatic stress disorder (PTSD), the role of
labour- and birth-related factors remains unclear. The present investigation
explored the impact of birth setting, subjective childbirth experience, and their
interplay, on PPD and postpartum PTSD. METHOD: in this prospective longitudinal
cohort study, three groups of women who had vaginal births at a tertiary care
hospital, a birthing center, and those transferred from the birthing centre to
the tertiary care hospital were compared. Participants were followed twice during
pregnancy (12-14 and 32-34 weeks gestation) and twice after childbirth (1-3 and 7
9 weeks postpartum). RESULTS: symptoms of PPD and PTSD did not significantly
differ between birth groups; however, measures of subjective childbirth
experience and obstetric factors did. Moderation analyses indicated a significant
interaction between pain and birth group, such that higher ratings of pain among
women who were transferred was associated with greater symptoms of postpartum
PTSD. CONCLUSION AND IMPLICATIONS FOR PRACTICE: women who are transferred appear
to have a unique experience that may put them at greater risk for postpartum
psychological distress. It may be beneficial for care providers to help prepare
women for pain management and potential unexpected complications, particularly if
it is their first childbirth.
PMID- 28412527
TI - Aquaporins as potential drought tolerance inducing proteins: Towards instigating
stress tolerance.
AB - Aquaporins (AQPs) are primarily involved in maintaining cellular water
homeostasis. Their role in diverse physiological processes has fascinated plant
scientists for more than a decade, particularly concerning abiotic stresses.
Increasing examples of evidence in various crop plants indicate that the AQPs are
responsible for precise regulation of water movement and consequently play a
crucial role in the drought stress tolerance. Since drought is one of the major
abiotic stresses affecting agricultural production worldwide, it has become a
critical agenda to focus research on the development of drought tolerant crop
plants. AQPs can act as key candidate molecules to confront this issue. Hence,
there is an important need to explore the potential of AQPs by understanding the
molecular mechanisms and pathways through which they induce drought tolerance.
Moreover, the signalling network/s involved in such pathways needs to be mined
and understood correctly, and that may lead to the development of drought
tolerance in crop plants. In the present review, opportunity and challenges
regarding the efficient utilization of AQP-related information is presented and
discussed. The complied information and the discussion will be helpful for
designing future experiments and to set the specific goals for the enhancement of
drought tolerance in crop plants. Biological Significance Knowledge on the role
of AQPs in maintaining cellular water homeostasis has given new hope for
developing drought tolerance in crop plants. Since drought is one of the major
abiotic stresses affecting agricultural production worldwide, it has become a
critical agenda to focus research on the development of drought-tolerant crop
plants. AQPs can act as key candidate molecules to solve this problem through
genetic engineering. For this, it is important to understand the molecular
mechanisms and inter-related pathways through which AQPs induce drought tolerance
and to explore the signaling network/s involved in such pathways.
PMID- 28412528
TI - The global strategy employed by Xanthomonas oryzae pv. oryzae to conquer low
oxygen tension.
AB - : Xanthomonas oryzae pv. oryzae (Xoo) is a notorious rice pathogen that causes
bacterial leaf blight (BLB), a destructive rice disease. Low-oxygen tension in
the xylem vessels of rice stresses Xoo during infection. In this study,
differentially expressed proteins under normoxic and hypoxic conditions were
identified using high-performance liquid chromatography (HPLC) coupled with LC
MS/MS to investigate the global effects of low oxygen environment on Xoo PXO99A.
A statistically validated list of 187 (normoxia) and 140 (hypoxia) proteins with
functional assignments was generated, allowing the reconstruction of central
metabolic pathways. Ten proteins involved in aromatic amino acid biosynthesis,
glycolysis, butanoate metabolism, propanoate metabolism and biological adhesion
were significantly modulated under low-oxygen tension. The genes encoded by these
proteins were in-frame deleted, and three of them were determined to be required
for full virulence in Xoo. The contributions of these three genes to important
virulence-associated functions, including extracellular polysaccharide, cell
motility and antioxidative ability, are presented. BIOLOGICAL SIGNIFICANCE: To
study how Xanthomonas oryzae pv. oryzae (Xoo) conquers low-oxygen tension in the
xylem of rice, we identified differentially expressed proteins under normoxic and
hypoxia. We found 140 proteins that uniquely expressed under the hypoxia were
involved in 33 metabolism pathways. We identified 3 proteins were required for
full virulence in Xoo and related to the ability of extracellular polysaccharide,
cell motility, and antioxidative. This study is helpful for broadening our
knowledge of the metabolism processed of Xoo in the xylem of rice.
PMID- 28412529
TI - Vertical string-pulling in green jays (Cyanocorax yncas).
AB - The cognition of green jays (Cyanocorax yncas), a non Corvus corvid species, was
investigated by using the string-pulling paradigm. Five adult green jays
performed a vertical string-pulling task in which they had to retrieve a worm
attached to the end of a vertical hanging string while sitting on their perch. In
the first experiment, three of the subjects managed to retrieve the worm by
pulling on the string with their beaks and stepping on the resulting loop, and
thereafter repeating this sequence until the worm was accessible. When subjects
were given a choice between two strings in subsequent experiments 2-4, they chose
at random between the string connected to the worm and the one connected to a
slice of a wooden dowel. In experiment 5, subjects that had failed the previous
discrimination series were able, nevertheless, to solve a more stringent vertical
string array in which they had to pull up the whole length of the string without
any visual access to the worm at the end. We discuss green jays' performance in
comparison with other corvid species in which cognition has been more extensively
investigated.
PMID- 28412530
TI - Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.
AB - Indoles constitute extensively explored heterocyclic ring systems with wide range
of applications in pathophysiological conditions that is, cancer, microbial and
viral infections, inflammation, depression, migraine, emesis, hypertension, etc.
Presence of indole nucleus in amino acid tryptophan makes it prominent in
phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones),
indole alkaloids etc. The interesting molecular architecture of indole makes them
suitable candidates for the drug development. This review article provides an
overview of the chemistry, biology, and toxicology of indoles focusing on their
application as drugs. Our effort is to corroborate the information available on
the natural indole alkaloids, indole based FDA approved drugs and clinical trial
candidates having diverse therapeutic implementations. This compiled information
may serve as a benchmark for the alteration of existing ligands to design novel
potent molecules with lesser side effects.
PMID- 28412531
TI - Vagus nerve is involved in the changes in body temperature induced by
intragastric administration of 1,8-cineole via TRPM8 in mice.
AB - Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by
mild cold temperature (<28 degrees C). TRPM8 expressed in cutaneous sensory
nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected
in various tissues, including the gastrointestinal mucosa, and in the vagal
afferent nerve. The relationship between vagal afferent nerve-specific expression
of TRPM8 and thermoregulation remains unclear. In this study, we aimed to
investigate whether TRPM8 expression in the vagal afferent nerve is involved in
autonomic thermoregulation. We found that intragastric administration of 1,8
cineole, a TRPM8 agonist, increased intrascapular brown adipose tissue and
colonic temperatures, and M8-B-treatment (TRPM8 antagonist) inhibited these
responses. Intravenous administration of 1,8-cineole also showed similar effects.
In vagotomized mice, the responses induced by intragastric administration of 1,8
cineole were attenuated. These results suggest that TRPM8 expressed in tissues
apart from cutaneous sensory nerves are involved in autonomic thermoregulation
response.
PMID- 28412532
TI - Spectral analysis highlight developmental EEG changes in preterm infants without
overt brain damage.
AB - Early markers of neurological outcome in the absence of overt brain damage are
scarce in extreme prematurity. The aim of this study was to compare spectral EEG
values of infants born near term with those of infants born at extremely low
gestational age (ELGA) but having attained near term age. We aimed also to
evaluate whether spectral EEG features were related with neurological outcome.
The ELGA group consisted of 12 neonates born between 23+2 and 27+6 weeks; the
control group consisted of nine infants born 34-35+2 weeks, tested within the
first week of life. All neonates underwent multichannel EEG recordings at 35
weeks post-conception. None of the subjects had apparent neurological
abnormalities or risk factors at the time of recording. EEG data were transformed
into the frequency domain and divided into delta (0.5-4Hz), theta (5-7Hz), alpha
(8-13Hz), beta (14-20Hz) frequency bands; relative EEG power values were
calculated. ELGA group was compared with the control group using a mixed analysis
of variance. Outcome was evaluated at one year of age by Griffiths' scales. A
principal effect of frequency and an interaction effect of frequency * group was
found. The total relative power of the delta band was significantly higher in
ELGA than in control group, whereas in the remaining frequency bands total
relative power was lower in ELGA than in control group. Higher values of delta
and lower values of alpha and beta spectral power correlated with poor outcome.
We provide preliminary results suggesting that, as early as 35 weeks post
conception, infants born extremely preterm fail to develop the age specific
pattern of EEG spectral activity, in the absence of neurological neonatal risk.
PMID- 28412533
TI - Print-specific N170 involves multiple subcomponents for Japanese Hiragana.
AB - Print-specific N170 in event-related potentials is generally considered to
reflect relatively automatic processing for letter strings, which is crucial for
fluent reading. However, our previous studies demonstrated that print-specific
N170 for transparent Japanese Hiragana script consists of at least two
subcomponents under rapid stimulus presentation: an attention-related left
lateralized N170 and a bilateral N170 associated with more automatic orthographic
processes (Okumura, Kasai & Murohashi, 2014, 2015). The present study aimed to
confirm the latter component by controlling presentation frequency of letters and
nonlinguistic visual controls (i.e., symbols), but found a quite different
pattern of results; an enhanced occipito-temporal positivity for words (80-120ms
poststimulus) followed by the typical left-lateralized N170 and an enhanced
parietal negativity for nonwords (150-200ms). These results should provide
further insights into the interaction processes between attention and early
stages of print processing.
PMID- 28412535
TI - Complex biogeographic scenarios revealed in the diversification of the largest
woodpecker radiation in the New World.
AB - Phylogenetic relationships and patterns of evolution within Melanerpes, one of
the most diverse groups of New World woodpeckers (22-23 lineages), have been
complicated due to complex plumages and morphological adaptations. In an attempt
to resolve these issues, we obtained sequence data from four nuclear introns and
two mitochondrial protein-coding genes for 22 of the 24 currently recognized
species in the genus. We performed phylogenetic analyses involving Maximum
Likelihood and Bayesian Inference, species-tree divergence dating, and
biogeographic reconstructions. Tree topologies from the concatenated and species
tree analyses of the mtDNA and nDNA showed broadly similar patterns, with three
relatively well-supported groups apparent: (a) the Sphyrapicus clade (four
species); (b) the typical Melanerpes clade, which includes temperate and
subtropical dry forest black-backed species; and (c) the mostly barred-backed
species, here referred to as the "Centurus" clade. The phylogenetic position of
Melanerpes superciliaris regarding the rest of Melanerpes is ambiguous as it is
recovered as sister to the rest of Melanerpes or as sister to a group including
Sphyrapicus+Melanerpes. Our species tree estimations recovered the same well
delimited highly-supported clades. Geographic range evolution (estimated in
BioGeoBEARS) was best explained by a DIVALIKE+j model, which includes vicariance,
founder effect speciation, and anagenetic dispersal (range expansion) as
important processes involved in the diversification of the largest radiation of
woodpeckers in the New World.
PMID- 28412534
TI - Isolation and identification of culturable bacteria, capable of heterotrophic
growth, from rapid sand filters of drinking water treatment plants.
AB - The microbial community in sand filters (SFs) of drinking water treatment plants
(DWTPs) likely contributes to SF functionalities, such as organic carbon removal
through heterotrophic metabolism. However, the dynamics and functionality of the
SF microbiome and microbial communities in oligotrophic freshwater environments
in general, are poorly understood. Therefore, the availability of bacterial
strains from these oligotrophic environments is of great interest, but such
organisms are currently underrepresented in culture collections. Focusing on
heterotrophic carbon metabolism, bacteria were isolated from SFs using
conventional media and media that contained SF extracts to mimic the SF
environment. The majority of isolates belonged to Betaproteobacteria, more
specifically to the families Comamonadaceae (genera Acidovorax, Curvibacter,
Hydrogenophaga, Simplicispira, Paucibacter, Pelomonas, Piscinibacter and
Rhodoferax) and Oxalobacteraceae (Undibacterium). Additionally, members of
Alphaproteobacteria (Mesorhizobium), Gammaproteobacteria (Aeromonas and
Perlucidibaca) and Actinobacteria (Rhodococcus and Brachybacterium) were
isolated. Several of those genera have only rarely been described, but appear
typical inhabitants of oligotrophic freshwater environments. In this regard, the
Comamonadaceae isolates are of particular interest. Our study shows that bacteria
representative of oligotrophic environments can be isolated using simple
isolation procedures. The isolates provide a microbial framework for extending
our knowledge of the taxonomy, physiology and functionality of oligotrophic
freshwater microbiomes and their interactions with possible invaders.
PMID- 28412536
TI - Molecular phylogenetics and dating of the problematic New Guinea microhylid frogs
(Amphibia: Anura) reveals elevated speciation rates and need for taxonomic
reclassification.
AB - Asterophryinae is a large monophyletic subfamily of Anurans containing over 300
species distributed across one of the world's most geologically active areas -
New Guinea and its satellite islands, Australia and the Philippines. The
tremendous ecological and morphological diversity of this clade, with apparent
specializations for burrowing, terrestrial, semi-aquatic, and arboreal lifestyle,
suggests an evolutionary process of adaptive radiation. Despite this spectacular
diversity, this and many other questions of evolutionary processes have received
little formal study because until now the phylogeny of this spececies-rich clade
has remained uncertain. Here we reconstruct a phylogeny for Asterophryinae with
greatly increased taxon and genetic sampling relative to prior studies. We use
Maximum Likelihood and Bayesian Inference methods to produce the most robust and
comprehensive phylogeny to date containing 155 species using 3 nuclear and 2
mitochondrial loci. We also perform a time calibration analysis to estimate the
age of the clade. We find support for the monophyly of Asterophryinae as well as
need for taxonomic reclassification of several genera. Furthermore, we find
increased rates of speciation across the clade supporting the hypothesis of rapid
radiation. Lastly, we found that adding taxa to the analysis produced more robust
phylogenetic results over adding loci.
PMID- 28412537
TI - Delivering effective science communication: advice from a professional science
communicator.
AB - Science communication is becoming ever more prevalent, with more and more
scientists expected to not only communicate their research to a wider public, but
to do so in an innovative and engaging manner. Given the other commitments that
researchers and academics are required to fulfil as part of their workload
models, it is unfair to be expect them to also instantly produce effective
science communication events and activities. However, by thinking carefully about
what it is that needs to be communicated, and why this is being done, it is
possible to develop high-quality activities that are of benefit to both the
audience and the communicator(s). In this paper, I present some practical advice
for developing, delivering and evaluating effective science communication
initiatives, based on over a decade of experience as being a professional science
communicator. I provide advice regarding event logistics, suggestions on how to
successfully market and advertise your science communication initiatives, and
recommendations for establishing effective branding and legacy.
PMID- 28412538
TI - Saharan dust intrusions in Spain: Health impacts and associated synoptic
conditions.
AB - BACKGROUND: A lot of papers have been published about the impact on mortality of
Sahara dust intrusions in individual cities. However, there is a lack of studies
that analyse the impact on a country and scarcer if in addition the analysis
takes into account the meteorological conditions that favour these intrusions.
OBJECTIVES: The main aim is to examine the effect of Saharan dust intrusions on
daily mortality in different Spanish regions and to characterize the large-scale
atmospheric circulation anomalies associated with such dust intrusions. METHODS:
For determination of days with Saharan dust intrusions, we used information
supplied by the Ministry of Agriculture, Food & Environment, it divides Spain
into 9 main areas. In each of these regions, a representative province was
selected. A time series analysis has been performed to analyse the relationship
between daily mortality and PM10 levels in the period from 01.01.04 to 31.12.09,
using Poisson regression and stratifying the analysis by the presence or absence
of Saharan dust advections. RESULTS: The proportion of days on which there are
Saharan dust intrusions rises to 30% of days. The synoptic pattern is
characterised by an anticyclonic ridge extending from northern Africa to the
Iberian Peninsula. Particulate matter (PM) on days with intrusions are associated
with daily mortality, something that does not occur on days without intrusions,
indicating that Saharan dust may be a risk factor for daily mortality. In other
cases, what Saharan dust intrusions do is to change the PM-related mortality
behaviour pattern, going from PM2.5. CONCLUSIONS: A study such as the one
conducted here, in which meteorological analysis of synoptic situations which
favour Saharan dust intrusions, is combined with the effect on health at a city
level, would seem to be crucial when it comes to analysing the differentiated
mortality pattern in situations of Saharan dust intrusions.
PMID- 28412539
TI - Laparoscopic Reoperative Antireflux Surgery Is More Cost-Effective than Open
Approach.
AB - BACKGROUND: We previously reported on the outcomes of laparoscopic and open
reoperative antireflux surgery. The aim of this study was to compare the costs of
these procedures. STUDY DESIGN: We performed a retrospective review. Financial
and procedure coding data were obtained using a cost accounting system. There
were 49 procedures in 46 patients (36 female and 10 male). There were 38
laparoscopic (including 4 conversions) and 11 open procedures (7 transabdominal
repairs and 4 gastric-preserving Roux-en-Y esophagojejunostomy). Values are
median and interquartile range (IQR) and mean costs. RESULTS: Median age was 54
years (IQR 49 to 67 years) for the laparoscopic group vs 56 years (IQR 50 to 65
years) for the open group (p = 0.675). Mean direct costs per case for the
laparoscopic group vs open group were $12,655 vs $24,636 (p < 0.002); operating
room costs: $3,788 vs $5,547 (p = 0.011); hospital room costs: $1,948 vs $6,438
(p < 0.005); and supply costs: $4,386 vs $5,386 (p = 0.077). Median duration of
the operation for the laparoscopic group was 185 minutes (IQR 147 to 254 minutes)
vs 308 minutes (IQR 259 to 416 minutes) for the open group (p < 0.002). Median
length of stay for the laparoscopic group was 3 days (IQR 2 to 4 days) vs 9 days
(IQR 8 to 14 days) for the open group (p < 0.001). There was no 30-day or in
hospital mortality. Excluding the 4 Roux-en-Y procedures, direct costs for the
laparoscopic group (n = 38) were $12,655 vs $23,678 for the transabdominal group
(n = 7) (p = 0.035); duration of operation: 185 minutes (IQR 147 to 254 minutes)
vs 292 minutes (IQR 218 to 309 minutes) (p = 0.003); and length of stay: 3 days
(IQR 2 to 4 days) vs 9 days (IQR 7 to 15 days) (p = 0.017). There were 3
recurrences in the laparoscopic group. Two were repaired laparoscopically and 1
required a gastric-preserving Roux-en-Y esophagojejunostomy because the patient
had undergone 2 earlier failed repairs. Including the cumulative costs of 3
recurrent hiatal hernia repairs, the driving force to reduce costs remained
length of stay, manifested by the costs of the hospital rooms. CONCLUSIONS:
Laparoscopic reoperative antireflux surgery is more cost-effective than open
repair. The laparoscopic approach, when feasible, should be considered the
surgical option for treatment of recurrent hiatal hernia in specialized
esophageal centers with highly experienced surgical teams.
PMID- 28412540
TI - Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but
not always.
AB - Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs
deputed to non-image forming functions of the eye such as synchronization of
circadian rhythms to light-dark cycle. These cells are characterized by unique
electrophysiological, anatomical and biochemical properties and are usually more
resistant than conventional RGCs to different insults, such as axotomy and
different paradigms of stress. We also demonstrated that these cells are
relatively spared compared to conventional RGCs in mitochondrial optic
neuropathies (Leber's hereditary optic neuropathy and Dominant Optic Atrophy).
However, these cells are affected in other neurodegenerative conditions, such as
glaucoma and Alzheimer's disease. We here review the current evidences that may
underlie this dichotomy. We also present our unpublished data on cell experiments
demonstrating that melanopsin itself does not explain the robustness of these
cells and some preliminary data on immunohistochemical assessment of mitochondria
in mRGCs.
PMID- 28412541
TI - Endothelin polymorphisms as a risk factor for cerebral aneurysm rebleeding
following aneurysmal subarachnoid hemorrhage.
AB - BACKGROUND: Aneurysm rebleeding following presentation with aneurysmal
subarachnoid hemorrhage (aSAH) is associated with high mortality and poor
functional outcome. While a substantial genetic contribution to aneurysm
formation and rupture is known, the genetic influence on the risk of rebleeding
is poorly understood. OBJECTIVE: To evaluate the role of common endothelin
polymorphisms in aneurysm rebleeding. PATIENTS AND METHODS: Blood sample from all
patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study
were used for genetic evaluation. The CARAS study prospectively enrolled aSAH
patients at two academic institutions in the United States from 2012 to 2015.
Common endothelin SNPs were detected using 5'exonnuclease (Taqman) genotyping
assays. Analysis of associations between endothelin single nucleotide
polymorphisms (SNP) and aneurysm rebleeding was performed. RESULTS: One hundred
and forty-nine aSAH patients were included. Acute spontaneous aneurysm rebleeding
occurred in 5 (3.4%) patients. Multivariable analysis identified the TT genotype
for EDN1 G/T SNP (rs2070699; OR 97.4, 95% CI 3.825-2479.984, p=0.006) as an
independent risk factor for aneurysm rebleeding. Aneurysm rebleeding was
associated with an unfavorable functional outcome (mRS 3-6) at last follow up in
all 5 patients. CONCLUSION: Aneurysm rebleeding following presentation with aSAH
was independently associated with the TT genotype of the EDN1 G/T SNP. All
patients with acute spontaneous aneurysm rebleeding suffered a poor functional
outcome at last follow up.
PMID- 28412542
TI - Reduction of retinal nerve fiber layer thickness in vigabatrin-exposed patients:
A meta-analysis.
AB - OBJECTIVE: Vigabatrin (VGB) is currently served as an effective adjunctive
therapy for patients with partial epilepsy worldwide. In this study, meta
analysis was conducted to comprehensively evaluate the changes in peripapillary
retinal nerve fiber layer (RNFL) thickness assessed by optical coherence
tomography (OCT) in epilepsy patients who were treated by VGB. MATERIAL AND
METHODS: Publications on PubMed, Wiley Online Library and the Elsevier Science
databases were searched by September 2016. The statistical analysis was performed
by RevMan 5.3 software. RESULTS: Four studies were identified, and 202 eyes in
VGB-exposed patients (VGB group) as well as 162 eyes in patients who never
received VGB treatment (NON-VGB group) were included. The studies demonstrated
that the total RNFL thickness is attenuated in VGB treated patients (weighted
mean differences in MUm, WMD=-15.96, 95% CI: -23.69 to -8.23, P<0.0001). RNFL
thickness in 3 quadrants were significantly reduced in VGB group: superior (WMD=
18.15, 95% CI: -23.31 to -12.98, P<0.00001), inferior (WMD=-23.19, 95% CI: -32.23
to -14.15, P<0.00001) and nasal (WMD=-19.29, 95% CI: -35.57 to -3.02, P=0.02).
However, the temporal RNFL thickness in these two groups showed no significant
difference: temporal (WMD=-2.41, 95% CI: -6.67 to 1.85, P=0.27). CONCLUSION:
Based on the meta-analysis, RNFL thickness appears to reduce in epilepsy patients
who received VGB treatment, and OCT could be a useful tool to help clinicians
assessing its retinal toxicity and guiding its dosage.
PMID- 28412543
TI - Diabetes and cardiovascular events in high-risk patients: Insights from a
multicenter registry in a middle-income country.
AB - AIMS: The aim of this study was to determine the rate of major clinical events
and its determinants in patients with previous cardiovascular event or not, and
with or without diabetes from a middle-income country. METHODS: REACT study is a
multicenter registry conducted between July 2010 and May 2013 in Brazil. Patients
were eligible if they were over 45years old and high cardiovascular risk.
Patients were followed for 12months; data were collected regarding adherence to
evidence-based therapies and occurrence of clinical events (all-cause mortality,
non-fatal cardiac arrest, myocardial infarction, or stroke). RESULTS: A total of
5006 subjects was included and analyzed in four groups: No diabetes and no
previous cardiovascular event, n=430; diabetes and no previous cardiovascular
event, n=1138; no diabetes and previous cardiovascular event, n=1747; and
diabetes and previous cardiovascular event, n=1691. Major clinical events in one
year follow-up occurred in 332 patients. A previous cardiovascular event was
associated with a higher risk of having another event in the follow-up (HR 2.31
95% CI 1.74-3.05, p<0.001), as did the presence of diabetes (HR 1.28 95% CI 1.10
1.73, p=0.005). In patients with diabetes,failure to reach HbA1c targetswas
related topoorer event-free survival compared to patients with good metabolic
control (HR 1.70 95% CI 1.01-2.84, p=0.044). CONCLUSIONS: In Brazil, diabetes
confers high risk for major clinical events, but this condition is not equivalent
to having a previous cardiovascular event. Moreover, not so strict targets for
HbA1c in patients with diabetes and previous cardiovascular events might be
considered.
PMID- 28412544
TI - Phosphorylation of WHIRLY1 by CIPK14 Shifts Its Localization and Dual Functions
in Arabidopsis.
AB - Plastid-to-nucleus retrograde signaling is critical for normal growth and
development in plants. The dual-function and dual-located ssDNA binding protein
WHIRLY1 (WHY1) has been proposed to coordinate the retrograde signaling from
plastids to the nucleus. However, the regulatory mechanism governing the
functional switch of WHY1 for mediating plastid-to-nucleus retrograde signaling
remains unknown. Here, we report that the Calcineurin B-Like-Interacting Protein
Kinase14 (CIPK14) interacts with and phosphorylates WHY1 in Arabidopsis.
Phosphorylation of WHY1 results in increased accumulation in the nucleus and
enhanced binding with the promoter of WRKY53, which encodes a key transcription
factor regulating leaf senescence in Arabidopsis. Transgenic plants
overexpressing CIPK14 showed an increased nuclear isoform but decreased plastid
isoform of WHY1, among which 95% of transgenic lines showed the stay-green
phenotype and 5% of lines showed the variegated pale-green phenotype.
Interestingly, the phenotypes of both types of transgenic plants could be
recovered by overexpression of plastid-form WHY1. In contrast, knockdown of
CIPK14 caused early senescence and even seedling-lethal phenotypes along with
elevated expression of senescence-related genes such as WRKY53, SAG12, and NDHF
but decreased expression of MER11, RAD50, and POR genes, which could be rescued
by overexpression of CIPK14 but not by overexpressing plastid-form or nuclear
form WHY1; the stay-green plants overexpressing CIPK14 showed reduced expression
of WRKY53, SAG12, NDHF, and large plastid rRNA. Consistently, the accumulation of
nuclear-form WHY1 was significantly reduced in the CIPK14 knockdown lines,
resulting in a low ratio of nuclear-/plastid-form WHY1. Taken together, our
results demonstrate that CIPK14 regulates the phosphorylation and organellar
distributions of WHY1 and pinpoint that CIPK14 may function as a cellular switch
between leaf senescence and plastid development for coordinating the
intercellular signaling in Arabidopsis.
PMID- 28412545
TI - DNA Topoisomerase 1 Prevents R-loop Accumulation to Modulate Auxin-Regulated Root
Development in Rice.
AB - R-loop structures (RNA:DNA hybrids) have important functions in many biological
processes, including transcriptional regulation and genome instability among
diverse organisms. DNA topoisomerase 1 (TOP1), an essential manipulator of DNA
topology during RNA transcription and DNA replication processes, can prevent R
loop accumulation by removing the positive and negative DNA supercoiling that is
made by RNA polymerases during transcription. TOP1 is required for plant
development, but little is known about its function in preventing co
transcriptional R-loop accumulation in various biological processes in plants.
Here we show that knockdown of OsTOP1 strongly affects rice development, causing
defects in root architecture and gravitropism, which are the consequences of
misregulation of auxin signaling and transporter genes. We found that R-loops are
naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1
is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets
the accurate expression levels of auxin-related genes by preventing the
overaccumulation of inherent R-loops. Our data reveal R-loops as important
factors in polar auxin transport and plant root development, and highlight that
OsTOP1 functions as a key to link transcriptional R-loops with plant hormone
signaling, provide new insights into transcriptional regulation of hormone
signaling in plants.
PMID- 28412546
TI - Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by
Promoting Nuclear Proteasome-Mediated HY5 Degradation.
AB - The process of cold acclimation is an important adaptive response whereby many
plants from temperate regions increase their freezing tolerance after being
exposed to low non-freezing temperatures. The correct development of this
response relies on proper accumulation of a number of transcription factors that
regulate expression patterns of cold-responsive genes. Multiple studies have
revealed a variety of molecular mechanisms involved in promoting the accumulation
of these transcription factors. Interestingly, however, the mechanisms implicated
in controlling such accumulation to ensure their adequate levels remain largely
unknown. In this work, we demonstrate that prefoldins (PFDs) control the levels
of HY5, an Arabidopsis transcription factor with a key role in cold acclimation
by activating anthocyanin biosynthesis, in response to low temperature. Our
results show that, under cold conditions, PFDs accumulate into the nucleus
through a DELLA-dependent mechanism, where they interact with HY5, triggering its
ubiquitination and subsequent degradation. The degradation of HY5 would result,
in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate
development of cold acclimation. These findings uncover an unanticipated nuclear
function for PFDs in plant responses to abiotic stresses.
PMID- 28412547
TI - Intracellular DNA sensing pathway of cGAS-cGAMP is decreased in human newborns
and young children.
AB - Newborns are highly susceptible to DNA virus infections, which may result from
the characteristics of neonatal innate immune systems. Here we analyzed for the
first time the development of innate immune sensing and signaling of
intracellular DNA virus infection in human newborns and young children. Both mRNA
and protein expression of cGAS, an intracellular DNA sensor, were shown to be
significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In
addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex
virus type 1 (HSV-1) or interferon-alpha (IFNalpha) stimulation. Furthermore,
production of the second messenger cGAMP and activation of the transcriptional
factor IRF3 was severely decreased in neonatal cord blood mononuclear cells
(CBMCs) or PBMCs compared with adults. In contrast, the downstream signaling
STING-TBK1-IRF3 appeared to be functional in neonatal PBMCs, as demonstrated by
the fact that IRF3 phosphorylation and IFNbeta production in these cells could be
activated by cGAMP. Intriguingly, decreased expression of cGAS in neonatal cells
can be rescued by DNA demethylation, with concomitant enhancement in IFNbeta
induction by HSV-1. Thus, cGAS restoration or STING stimulation by small
molecules during infancy might improve the age-dependent susceptibility to DNA
virus infection.
PMID- 28412548
TI - Internal image anti-idiotypic antibody: A new strategy for the development a new
category of prolactin receptor (PRLR) antagonist.
AB - Over the past decades, a number of prolactin receptor (PRLR) antagonists have
been developed, which can be divided into two categories, PRLR analogue and anti
PRLR antibody. However, until now, there have been no commercially available PRLR
antagonists. Here, we described a new approach for the preparation of PRLR
antagonist, namely internal image anti-idiotypic antibody strategy. The hybridoma
technique was used to generate anti-idiotypic antibodies to PRL. Competitive
ELISA, competitive receptor-binding analysis and immunofluorescence assay (IFA)
were then used to screen and characterize anti-idiotypic antibodies to PRL. One
internal image anti-idiotypic antibody, termed MG7, was obtained. A series of
experiments demonstrated that MG7 behaved as a typical internal image anti
idiotypic antibody (Ab2beta). MG7 exhibited effective antagonistic activity,
which not only inhibited PRL binding to PRLR in a dose-dependent manner but also
inhibited PRLR-mediated intracellular signalling. Furthermore, MG7 also blocked
Nb2 cell proliferation induced by PRL. The current study suggests that MG7 has
the potential application in the PRL/PRLR-related studies in future. In addition,
this work also suggests that the internal image anti-idiotypic antibody may
represent a novel strategy for the development of PRLR antagonist.
PMID- 28412549
TI - Enhancing boron rejection in FO using alkaline draw solutions.
AB - This study provides a novel method to enhance boron removal in a forward osmosis
(FO) process. It utilizes the reverse solute diffusion (RSD) of ions from
alkaline draw solutions (DSs) and the concentration polarization of the hydroxyl
ions to create a highly alkaline environment near the membrane active surface.
The results show that boron rejection can be significantly enhanced by increasing
the pH of NaCl DS to 12.5 in the active-layer-facing-feed-solution (AL-FS)
orientation. The effect of RSD enhanced boron rejection was further promoted in
the presence of concentration polarization (e.g., in the active-layer-facing-draw
solution (AL-DS) orientation). The current study opens a new dimension for
controlling contaminant removal by FO using tailored DS chemistry, where the RSD
induced localized water chemistry change is taken advantage in contrast to the
conventional method of chemical dosing to the bulk feed water.
PMID- 28412550
TI - The competition between cathodic oxygen and ozone reduction and its role in
dictating the reaction mechanisms of an electro-peroxone process.
AB - Previous studies indicate that effective generation of hydrogen peroxide (H2O2)
from cathodic oxygen (O2) reduction is critical for the improved water treatment
performance (e.g., enhanced pollutant degradation and reduced bromate formation)
during the electro-peroxone (E-peroxone) process (a combined process of
electrolysis and ozonation). However, undesired reactions (e.g., O3, H2O2, and
H2O reductions) may occur in competition with O2 reduction at the cathode. To get
a better understanding of how these side reactions would affect the process, this
study investigated the cathodic reaction mechanisms during electrolysis with
O2/O3 gas mixture sparging using various electrochemical techniques (e.g., linear
sweep voltammetry and stepped-current chronopotentiometry). Results show that
when a carbon brush cathode was used during electrolysis with O2/O3 sparging, H2O
and H2O2 reductions were usually negligible cathodic reactions. However, O3 can
be preferentially reduced at much more positive potentials (ca. 0.9 V vs. SCE)
than O2 (ca. -0.1 V vs. SCE) at the carbon cathode. Therefore, cathodic O2
reduction was inhibited when the process was operated under current limited
conditions for cathodic O3 reduction. The inhibition of O2 reduction prevented
the desired E-peroxone process (cathodic O2 reduction to H2O2 and ensuing
reaction of H2O2 with O3 to OH) from occurring. In contrast, when cathodic O3
reduction was limited by O3 mass transfer to the cathode, cathodic O2 reduction
to H2O2 could occur, thus enabling the E-peroxone process to enhance pollutant
degradation and mineralization. Many process and water parameters (applied
current, ozone dose, and reactivity of water constituents with O3) can cause
fundamental changes in the cathodic reaction mechanisms, thus profoundly
influencing water treatment performance during the E-peroxone process. To exploit
the benefits of H2O2 in water treatment, reaction conditions should be carefully
controlled to promote cathodic O2 reduction during the E-peroxone process.
PMID- 28412551
TI - A field experiment to evaluate the cleaning performance of sewer flushing on non
uniform sediment deposits.
AB - The results of a field experiment to evaluate the scouring effect of a single
flush operation in a compound-section sewer channel in Paris, France, are
presented in this paper. Full monitoring of the experiment allowed identifying
flush-related transport/deposition key processes playing a role on the evolution
of the deposited sediments. Overall, the flush was able to scour sediments
accumulated over the channel invert up to a significant distance from the gate.
The analysis of the results revealed that the flush had a different impact on the
various sediments present in the bed mixtures, with most of the eroded volume
including sediment particles smaller than the median grain size.
PMID- 28412552
TI - Copper-containing mesoporous bioactive glass nanoparticles as multifunctional
agent for bone regeneration.
AB - : The application of mesoporous bioactive glasses (MBGs) containing controllable
amount of different ions, with the aim to impart antibacterial activity, as well
as stimulation of osteogenesis and angiogenesis, is attracting an increasing
interest. In this contribution, in order to endow nano-sized MBG with additional
biological functions, the framework of a binary SiO2-CaO mesoporous glass was
modified with different concentrations of copper ions (2 and 5%mol.), through a
one-pot ultrasound-assisted sol-gel procedure. The Cu-containing MBG (2%mol.)
showed high exposed surface area (550m2g-1), uniform mesoporous channels (2.6nm),
remarkable in vitro bioactive behaviour and sustained release of Cu2+ ions. Cu
MBG nanoparticles and their ionic dissolution extracts exhibited antibacterial
effect against three different bacteria strains, E. coli, S. aureus, S.
epidermidis, and the ability to inhibit and disperse the biofilm produced by S.
epidermidis. The obtained results suggest that the developed material, which
combines in single multifunctional agent excellent bioactivity and antimicrobial
ability, offers promising opportunities for the prevention of infectious diseases
and the effective treatment of bone defects. STATEMENT OF SIGNIFICANCE: In order
to endow mesoporous bioactive glass, characterized by excellent bioactive
properties, with additional biological functions, Cu-doped mesoporous SiO2-CaO
glass (Cu-MBG) in the form of nanoparticles was prepared by an ultra-sound
assisted one pot synthesis. The analysis of the bacterial viability, using
different bacterial strains, and the morphological observation of the biofilm
produced by the Staphylococcus epidermidis, revealed the antimicrobial
effectiveness of the Cu-MBG and the relative ionic extracts against both the
bacterial growth and the biofilm formation/dispersion, providing a true
alternative to traditional antibiotic systemic therapies. The proposed
multifunctional agent represents a promising and versatile platform for bone and
soft tissues regeneration.
PMID- 28412553
TI - Native and solubilized decellularized extracellular matrix: A critical assessment
of their potential for improving the expansion of mesenchymal stem cells.
AB - : Capturing the promise of mesenchymal stem cell (MSC)-based treatments is
currently limited by inefficient production of cells needed for clinical
therapies. During conventional ex vivo expansion, a large portion of MSCs lose
the properties that make them attractive for use in cell therapies.
Decellularized extracellular matrix (dECM) has recently emerged as a promising
substrate for the improved expansion of MSCs. MSCs cultured on these surfaces
exhibit improved proliferation capacity, maintenance of phenotype, and increased
differentiation potential. Additionally, these dECMs can be solubilized and used
to coat new cell culture surfaces, imparting key biological properties of the
native matrices to other surfaces such as tissue engineering scaffolds. Although
this technology is still developing, there is potential for an impact in the
fields of MSC biology, biomaterials, tissue engineering, and therapeutics. In
this article, we review the role of dECM in MSC expansion by first detailing the
decellularization methods that have been used to produce the dECM substrates;
discussing the shortcomings of current decellularization methods; describing the
improved MSC characteristics obtained when the cells are cultured on these
surfaces; and considering the effect of the passage number, age of donor, and
dECM preparation method on the quality of the dECM. Finally we describe the
critical roadblocks that must be addressed before this technology can fulfil its
potential, including elucidating the mechanism by which the dECMs improve the
expansion of primary MSCs and the identification of a readily available source of
dECM. STATEMENT OF SIGNIFICANCE: Current mesenchymal stem cell (MSC) culture
methods result in premature cellular senescence or loss of differentiation
potential. This creates a major bottleneck in their clinical application, as
prolonged expansion is necessary to achieve clinically relevant numbers of cells.
Recently, decellularized extracellular matrix (dECM) produced by primary MSC has
emerged as an attractive substrate for the improved expansion of MSC; cells
cultured on these surfaces retain their desired stem cell characteristics for
prolonged times during culture. This review article describes the inception and
development of this dECM-based technology, points out existing challenges that
must be addressed, and suggests future directions of research. To our knowledge,
this is the first review written on the use of dECM for improved mesenchymal stem
cell expansion.
PMID- 28412554
TI - Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin
nanofiber hydrogel.
AB - : Fibrin plays a crucial role in peripheral nerve regeneration, which could occur
spontaneously in the format of longitudinally oriented fibrin cables during the
initial stage of nerve regeneration. This fibrin cable can direct migration and
proliferation of Schwann cells and axonal regrowth, which is very important to
nerve regeneration. In the present study, we prepared a three-dimensional
hierarchically aligned fibrin nanofiber hydrogel (AFG) through electrospinning
and molecular self-assembly to resemble the architecture and biological function
of the native fibrin cable. The AFG displayed a hierarchically aligned topography
as well as low elasticity (~1.5kPa) that were similar to nerve extracellular
matrix (ECM) and the native fibrin cable. Rapid, directional cell adhesion and
migration of Schwann cells (SCs) and dorsal root ganglions were observed in
vitro. The AFG was then used as a potential intraluminal substrate in a
bioengineered chitosan tube to bridge a 10-mm-long sciatic nerve gap in rats. We
found that the AFG served as a beneficial microenvironment to support SCs cable
formation and axonal regrowth within 2weeks. Further histological and
morphological analyses as well as electrophysiological and functional
examinations were performed after AFG implantation for up to 12weeks. The results
from morphological analysis and electrophysiological examination indicated that
regenerative outcomes achieved by our developed graft were close to those by an
autologous nerve graft, but superior to those by hollow chitosan tubes (hCST) and
random fibrin nanofiber hydrogel (RFG). Our results demonstrate that the AFG
creates an instructive microenvironment by mimicking the native fibrin cable as
well as the oriented and soft features of nerve ECM to accelerate axonal
regrowth, thus showing great promising potential for applications in neural
regeneration. STATEMENT OF SIGNIFICANCE: In peripheral nervous system defect
repair, a wide variety of strategies have been proposed for preparing
functionalized nerve guidance conduits (NGC) with more complex configurations to
obtain optimal repair effects. Longitudinally oriented fibrin cables were
reported to form spontaneously during the initial stages of peripheral nerve
regeneration in an empty NGC, which can direct the migration and proliferation of
Schwann cells and promote axonal regrowth. Therefore, based on the biomimetic
idea, we prepared a three-dimensional hierarchically aligned fibrin nanofiber
hydrogel (AFG) through electrospinning and molecular self-assembly, resembling
the architecture and biological function of the native fibrin cable and serving
as an intraluminal filling to accelerate axon regeneration. We found that the AFG
was a beneficial microenvironment to support SCs cable formation and accelerate
axonal regrowth with improved motor functional recovery.
PMID- 28412555
TI - One-dimensional poly(L-lysine)-block-poly(L-threonine) assemblies exhibit potent
anticancer activity by enhancing membranolysis.
AB - : Herein, we report the oncolytic activity of cationic, one-dimensional (1D)
fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine)
(PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can
efficiently interact with negatively charged cellular and mitochondrial membranes
via electrostatic interactions, leading to necrosis via membrane lysis and
apoptosis via the mitochondria-lytic effect. The concept is analogous to that of
1D drug carriers that exhibit enhanced cell penetration. In comparison to free
PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward
cancer cells, low hemolysis activity, enhanced membranolytic activity, and a
different apoptosis pathway, which may be due to differences in the peptide
membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma
model indicate that the fibril assemblies significantly inhibited tumor growth,
improved survival in tumor-bearing mice and suppressed lung metastasis without
obvious body weight loss. An additive efficacy was also observed for treatment
with both PLL-b-PLT and cisplatin. These results support the feasibility of using
1D fibril assemblies as potential apoptotic anticancer therapeutics. STATEMENT OF
SIGNIFICANCE: We report that cationic, one-dimensional (1D) fibril assemblies
formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block
copolypeptides exhibited potent anticancer activity by enhancing membranolysis.
The 1D fibril assemblies can efficiently interact with negatively charged
cellular and mitochondrial membranes via electrostatic interactions, leading to
necrosis via membrane lysis and apoptosis via mitochondria-lytic effect.
Moreover, the fibril assemblies exhibited low hemolytic activity and selective
cytotoxicity toward cancer cell, which is advantageous as compared to PLL and
most antimicrobial/anticancerous peptides. This study provides a new concept of
using cationic, 1D fibril assemblies for cancer therapy.
PMID- 28412556
TI - Synchronized movement experience enhances peer cooperation in preschool children.
AB - Cooperating with other people is a key achievement in child development and is
essential for human culture. We examined whether we could induce 4-year-old
children to increase their cooperation with an unfamiliar peer by providing the
peers with synchronized motion experience prior to the tasks. Children were
randomly assigned to independent treatment and control groups. The treatment of
synchronous motion caused children to enhance their cooperation, as measured by
the speed of joint task completion, compared with control groups that underwent
asynchronous motion or no motion at all. Further analysis suggested that
synchronization experience increased intentional communication between peer
partners, resulting in increased coordination and cooperation.
PMID- 28412557
TI - Electroconvulsive therapy changes the regional resting state function measured by
regional homogeneity (ReHo) and amplitude of low frequency fluctuations (ALFF) in
elderly major depressive disorder patients: An exploratory study.
AB - Electroconvulsive therapy (ECT) is the most effective and rapid treatment for
severe major depressive disorder (MDD) in elderly patients. The mechanism of ECT
is unclear, and studies on ECT in elderly MDD patients by resting-state
functional magnetic resonance imaging are rare. Thirteen elderly MDD patients
were scanned before and after ECT using a 3.0T MRI scanner. Regional homogeneity
(ReHo) and amplitude of low-frequency fluctuations (ALFF) were processed to
compare resting-state function before and after treatment. Depression and anxiety
symptoms of all patients abated after ECT. Decreased ReHo values in the bilateral
superior frontal gyrus (SFG) were observed after ECT, and the values of right SFG
significantly correlated with an altered Hamilton depression rating scale score.
Increased ALFF values in the left middle frontal gyrus, right middle frontal
gyrus, orbital part, and decreased ALFF values in the left midcingulate area,
left precentral gyrus, right SFG/middle frontal gyrus after ECT were also
observed. These results support the hypothesis that ECT may affect the regional
resting state brain function in geriatric MDD patients.
PMID- 28412558
TI - Relationship of mindful awareness to neural processing of angry faces and impact
of mindfulness training: A pilot investigation.
AB - Mindfulness is paying attention, non-judgmentally, to experience in the moment.
Mindfulness training reduces depression and anxiety and influences neural
processes in midline self-referential and lateralized somatosensory and executive
networks. Although mindfulness benefits emotion regulation, less is known about
its relationship to anger and the corresponding neural correlates. This study
examined the relationship of mindful awareness and brain hemodynamics of angry
face processing, and the impact of mindfulness training. Eighteen healthy
volunteers completed an angry face processing fMRI paradigm and measurement of
mindfulness and anger traits. Ten of these participants were recruited from a
Mindfulness-Based Stress Reduction (MBSR) class and also completed imaging and
other assessments post-training. Self-reported mindful awareness increased after
MBSR, but trait anger did not change. Baseline mindful awareness was negatively
related to left inferior parietal lobule activation to angry faces; trait anger
was positively related to right middle frontal gyrus and bilateral angular gyrus.
No significant pre-post changes in angry face processing were found, but changes
in trait mindful awareness and anger were associated with sub-threshold
differences in paralimbic activation. These preliminary and hypothesis-generating
findings, suggest the analysis of possible impact of mindfulness training on
anger may begin with individual differences in angry face processing.
PMID- 28412559
TI - Interictal ripples nested in epileptiform discharge help to identify the
epileptogenic zone in neocortical epilepsy.
AB - OBJECTIVE: This study aimed to identify the subtype of interictal ripples that
help delineate the epileptogenic zone in neocortical epilepsy. METHODS: Totally
25 patients with focal neocortical epilepsy who had invasive
electroencephalography (EEG) evaluation and subsequent surgery were included.
They were followed up for at least 2years. Interictal ripples (80-250Hz) and fast
ripples (250-500Hz) during slow-wave sleep were identified. Neocortical ripples
were defined as type I ripples when they were superimposed on epileptiform
discharges, and as type II ripples when they occurred independently. Resection
ratio was calculated to present the extent to which the cortical area showing an
interictal event or the seizure onset zone (SOZ) was completely removed. RESULTS:
Fast ripples and types I and II ripples were found in 8, 19, and 21 patients,
respectively. Only the higher resection ratio of interictal fast or type I
ripples was correlated to the Engel 1a surgical outcome. CONCLUSIONS: Type I
ripples could assist in localizing the epileptogenic zone in neocortical
epilepsy. SIGNIFICANCE: Type I and fast ripples both may be pathological high
frequency oscillations.
PMID- 28412560
TI - Comparison of minimally invasive spine surgery using intraoperative computed
tomography integrated navigation, fluoroscopy, and conventional open surgery for
lumbar spondylolisthesis: a prospective registry-based cohort study.
AB - BACKGROUND CONTEXT: To date, the surgical approaches for the treatment of lumbar
spondylolisthesis by transforaminal lumbar interbody fusion (TLIF) using
minimally invasive spine surgery assisted with intraoperative computed tomography
image-integrated navigation (MISS-iCT), fluoroscopy (MISS-FS), and conventional
open surgery (OS) are debatable. PURPOSE: This study compared TLIF using MISS
iCT, MISS-FS, and OS for treatment of one-level lumbar spondylolisthesis. STUDY
DESIGN: This is a prospective, registry-based cohort study that compared surgical
approaches for patients who underwent surgical treatment for one-level lumbar
spondylolisthesis. PATIENT SAMPLE: One hundred twenty-four patients from January
2010 to March 2012 in a medical center were recruited. OUTCOME MEASURES: The
outcome measures were clinical assessments, including Short-Form 12, visual
analog scale (VAS), Oswestry Disability Index, Core Outcome Measurement Index,
and patient satisfaction, and blood loss, hospital stay, operation time,
postoperative pedicle screw accuracy, and superior-level facet violation.
METHODS: All surgeries were performed by two senior surgeons together. Ninety
nine patients (40M, 59F) who had at least 2 years' follow-up were divided into
three groups according to the operation methods: MISS-iCT (N=24), MISS-FS (N=23),
and OS (N=52) groups. Charts and surgical records along with postoperative CT
images were assessed. RESULTS: MISS-iCT and MISS-FS demonstrated a significantly
lowered blood loss and hospital stay compared with OS group (p<.01). Operation
time was significantly lower in the MISS-iCT and OS groups compared with the MISS
FS group (p=.002). Postoperatively, VAS scores at 1 year and 2 years were
significantly improved in the MISS-iCT and MISS-FS groups compared with the OS
groups. No significant difference in the number of pedicle screw breach (>2 mm)
was found. However, a lower superior-level facet violation rate was observed in
the MISS-iCT and OS groups (p=.049). CONCLUSIONS: MISS-iCT TLIF demonstrated
reduced operation time, blood loss, superior-level facet violation, hospital
stay, and improved functional outcomes compared with the MISS-FS and OS
approaches.
PMID- 28412562
TI - Effectiveness of telehealth-based interventions in the management of non-specific
low back pain: a systematic review with meta-analysis.
AB - BACKGROUND: Telehealth has emerged as a potential alternative to deliver
interventions for low back pain (LBP); however, its effectiveness has not been
investigated. PURPOSE: The aim of this review was to evaluate whether
interventions delivered by telehealth improve pain, disability, function, and
quality of life in non-specific LBP. STUDY DESIGN: This is a systematic review
with meta-analysis. METHODS: Seven databases were searched from the earliest
records to August 2015. Eligible studies were randomized controlled trials that
investigated the effectiveness of telehealth-based interventions, solo or in
combination with other interventions, for non-specific LBP compared with a
control group. Trials deemed clinically homogeneous were grouped in meta
analyses. RESULTS: Eleven studies were included (n=2,280). In chronic LBP,
telehealth interventions had no significant effect on pain at short-term follow
up (four trials: 1,089 participants, weighted mean difference [WMD]: -2.61
points, 95% confidence interval [CI]: -5.23 to 0.01) or medium-term follow-up
(two trials: 441 participants, WMD: -0.94 points, 95% CI: -6.71 to 4.84) compared
with a control group. Similarly, there was no significant effect for disability.
Results from three individual trials showed that telehealth was superior to a
control intervention for improving quality of life. Interventions combining
telehealth and usual care were more beneficial than usual care alone in people
with recent onset of LBP symptoms. CONCLUSION: There is moderate-quality evidence
that current telehealth interventions, alone, are not more effective than minimal
interventions for reducing pain and disability in chronic LBP. To date, modern
telehealth media (eg, apps) and telehealth as an adjunct to usual care remain
understudied.
PMID- 28412561
TI - Metastatic human breast cancer to the spine produces mechanical hyperalgesia and
gait deficits in rodents.
AB - BACKGROUND CONTEXT: Metastases to the spine are a common source of severe pain in
cancer patients. The secondary effects of spinal metastases include pain, bone
fractures, hypercalcemia, and neurological deficits. As the disease progresses,
pain severity can increase until it becomes refractory to medical treatments and
leads to a decreased quality of life for patients. A key obstacle in the study of
pain-induced spinal cancer is the lack of reliable and reproducible spine cancer
animal models. In the present study, we developed a reproducible and reliable rat
model of spinal cancer using human-derived tumor tissue to evaluate neurological
decline using imaging and behavioral techniques. PURPOSE: The present study
outlines the development and characterization of an orthotopic model of human
breast cancer to the spine in immunocompromised rats. STUDY DESIGN/SETTING: This
is a basic science study. METHODS: Female immunocompromised rats were randomized
into three groups: tumor (n=8), RBC3 mammary adenocarcinoma tissue engrafted in
the L5 vertebra body; sham (n=6), surgery performed but not tumor engrafted; and
control (n=6), naive rats, no surgery performed. To evaluate the neurological
impairment due to tumor invasion, functional assessment was done in all rodents
at day 40 after tumor engraftment using locomotion gait analysis and pain
response to a mechanical stimulus (Randall-Selitto test). Bioluminescence (BLI)
was used to evaluate tumor growth in vivo and cone beam computed tomography
(CBCT) was performed to evaluate bone changes due to tumor invasion. The animals
were euthanized at day 45 and their spines were harvested and processed for
hematoxylin and eosin (H&E) staining. RESULTS: Tumor growth in the spine was
confirmed by BLI imaging and corroborated by histological analysis. Cone beam
computed tomography images were characterized by a decrease in the bone intensity
in the lumbar spine consistent with tumor location on BLI. On H&E staining of
tumor-engrafted animals, there was a near-complete ablation of the ventral and
posterior elements of the L5 vertebra with severe tumor invasion in the bony
components displacing the spinal cord. Locomotion gait analysis of tumor
engrafted rats showed a disruption in the normal gait pattern with asignificant
reduction in length (p=.02), duration (p=.002), and velocity (p=.002) of right
leg strides and only in duration (p=.0006) and velocity (p=.001) of left leg
strides, as compared with control and sham rats. Tumor-engrafted animals were
hypersensitive to pain stimulus shown as a significantly reduced response in time
(p=.02) and pressure (p=.01) applied when compared with control groups.
CONCLUSIONS: We developed a system for the quantitative analysis of pain and
locomotion in an animal model of metastatic human breast cancer of the spine.
Tumor-engrafted animals showed locomotor and sensory deficits that are in
accordance with clinical manifestation in patients with spine metastasis. Pain
response and locomotion gait analysis were performed during follow-up. The
Randall-Selitto test was a sensitive method to evaluate pain in the rat's spine.
We present a model for the study of bone-associated cancer pain secondary to
cancer metastasis to the spine, as well as for the study of new therapies and
treatments to lessen pain from metastatic cancer to the neuroaxis.
PMID- 28412563
TI - How are patients influenced when counseled for minimally invasive lumbar spine
surgeries? A stepwise model assessing pivotal information for decision-making.
AB - BACKGROUND CONTEXT: Although minimally invasive surgery (MIS)-transforaminal
lumbar interbody fusion (TLIF) has many evidence-based short-term benefits over
open TLIF, both procedures have similar long-term outcomes. Patients' preference
for MIS over open TLIF may be confounded by a lack of understanding of what each
approach entails. PURPOSE: The study aimed to identify the various factors
influencing patients' choice between MIS and open TLIF. STUDY DESIGN/SETTING:
This is a cross-sectional study conducted at a tertiary health-care institution.
PATIENT SAMPLE: Patients, for whom TLIF procedures were indicated, were recruited
over a 3-month period from specialist outpatient clinics. OUTCOME MEASURE: The
outcome measure was patients' choice of surgical approach (MIS or open). METHODS:
All patients were subjected to a stepwise interviewing process and were asked to
select between open and MIS approaches at each step. Further subgroup analysis
stratifying subjects based on stages of decision-making was performed to identify
key predictors of selection changes. No sources of funding were required for this
study and there are no conflicts of interests. RESULTS: Fifty-four patients with
a mean age of 55.8 years participated in the study. Thirteen (24.1%) consistently
selected a single approach, whereas 31 (57.4%) changed their selection more than
once during the interviewing process. Overall, 12 patients (22.2%) had a final
decision different from their initial choice, and 15 patients (27.8%) were unable
to decide. A large proportion of patients (65.0%) initially favored the open
approach's midline incision. This proportion dropped to 16.7% (p<.001) upon
mention of the term MIS. The proportion of patients favoring MIS dropped
significantly following discussion on the pros and cons (p=.002) of each
approach, as well as conversion or revision surgery (p=.017). Radiation and
cosmesis were identified as the two most important factors influencing patients'
final decisions. CONCLUSIONS: The longer midline incision of the open approach is
cosmetically more appealing to patients than the paramedian stab wounds of MIS.
The advantages of the MIS approach may not be as valued by patients as they are
by surgeons. Given the equivalent long-term outcomes of both approaches, it is
crucial that patients are adequately informed during preoperative counseling to
achieve the best consensus decision.
PMID- 28412564
TI - Outcomes of patients with syringomyelia undergoing spine deformity surgery: do
large syrinxes behave differently from small?
AB - BACKGROUND CONTEXT: A paucity of data exists studying outcomes of patients with
syringomyelia undergoing spinal deformity correction. The literature does not
stratify patients by syrinx size, which is likely a major contributor to
outcomes. PURPOSE: The study aimed to compare differences in outcomes between
patients with large (>=4 mm) and small syrinxes (<4 mm) undergoing spinal
deformity correction. DESIGN: This is a retrospective review. PATIENT SAMPLE: The
sample included 28 patients (11 with large syrinx [LS, >4 mm] and 17 with small
syrinx [SS, <4 mm]). OUTCOME MEASURES: The outcome measures were radiographic,
operative, and neurophysiological measures. METHODS: We retrospectively reviewed
28 patients with syringomyelia who underwent spine deformity surgery with 2-year
follow-up. Demographic, surgical, and radiographic data were collected and
compared preoperatively and at 2 years. RESULTS: The LS group (11 patients)
trended toward more left-sided thoracic curves (36% vs. 18%, p=.38) and was more
likely to have had a Chiari decompression (45% vs. 12%, p=.08). The LS patients
had larger preoperative major curves (LS=66 degrees vs. SS=57 degrees , p=.05),
more thoracic kyphosis (LS=42 degrees , SS=24 degrees , p<.01), and greater rib
prominences (LS=16 degrees , SS=13 degrees , p=.04). The LS patients had more
levels fused (LS=12.2, SS=11.2, p=.05), higher estimated blood loss (EBL)
(LS=1068 cc, SS=832 cc, p=.04), and a trend toward less percent correction of the
major curve (LS=57%, SS=65%, p=.18). Four of 11 LS patients (36%) did not have
somatosensory evoked potentials, and one of these also did not have motor evoked
potentials. Neuromonitoring changes occurred in 3 of 11 (27%) LS patients and in
none of the SS patients, with no postoperative deficits. CONCLUSIONS: Outcomes of
patients with syringomyelia undergoing spine deformity surgery are dependent on
the size of the syrinx. Those with large syringomyelia are fused longer with more
EBL and less correction. Spine surgeons should be aware that these patients are
more likely to have less reliable neuromonitoring, with a higher chance of
experiencing a change.
PMID- 28412565
TI - The use of a novel perfusion-based cadaveric simulation model with cerebrospinal
fluid reconstitution comparing dural repair techniques: a pilot study.
AB - BACKGROUND CONTEXT: Watertight dural repair is crucial for both incidental
durotomy and closure after intradural surgery. PURPOSE: The study aimed to
describe a perfusion-based cadaveric simulation model with cerebrospinal fluid
(CSF) reconstitution and to compare spine dural repair techniques. STUDY
DESIGN/SETTING: The study is set in a fresh tissue dissection laboratory. SAMPLE
SIZE: The sample includes eight fresh human cadavers. OUTCOME MEASURES: A
watertight closure was achieved when pressurized saline up to 40 mm Hg did not
cause further CSF leakage beyond the suture lines. METHODS: Fresh human cadaveric
specimens underwent cannulation of the intradural cervical spine for intrathecal
reconstitution of the CSF system. The cervicothoracic dura was then exposed from
C7-T12 via laminectomy. The entire dura was then opened in six cadavers
(ALLSPINE) and closed with 6-0 Prolene (n=3) or 4-0 Nurolon (n=3), and
pressurized with saline via a perfusion system to 60 mm Hg to check for leakage.
In two cadavers (INCISION), six separate 2-cm incisions were made and closed with
either 6-0 Prolene or 4-0 Nurolon, and then pressurized. A hydrogel sealant was
then added and the closure was pressurized again to check for further leakage.
RESULTS: Spinal laminectomy with repair of intentional durotomy was successfully
performed in eight cadavers. The operative microscope was used in all cases, and
the model provided a realistic experience of spinal durotomy repair. For ALLSPINE
cadavers (mean: 240 mm dura/cadaver repaired), the mean pressure threshold for
CSF leakage was observed at 66.7 (+/-2.9) mm Hg in the 6-0 Prolene group and at
43.3 (+/-14.4) mm Hg in the 4-0 Nurolon group (p>.05). For INCISION cadavers, the
mean pressure threshold for CSF leakage without hydrogel sealant was
significantly higher in 6-0 Prolene group than in the 4-0 Nurolon group (6-0
Prolene: 80.0+/-4.5 mm Hg vs. 4-0 Nurolon: 32.5+/-2.7 mm Hg; p<.01). The mean
pressure threshold for CSF leakage with the hydrogel sealants was not
significantly different (6-0 Prolene: 100.0+/-0.0 mm Hg vs. 4-0 Nurolon: 70.0+/
33.1 mm Hg). The use of a hydrogel sealant significantly increased the pressure
thresholds for possible CSF leakage in both the 6-0 Prolene group (p=.01) and the
4-0 Nurolon group (p<.01) when compared with mean pressures without the hydrogel
sealant. CONCLUSIONS: We described the feasibility of using a novel cadaveric
model for both the study and training of watertight dural closure techniques. 6-0
Prolene was observed to be superior to 4-0 Nurolon for watertight dural closure
without a hydrogel sealant. The use of a hydrogel sealant significantly improved
watertight dural closures for both 6-0 Prolene and 4-0 Nurolon groups in the
cadaveric model.
PMID- 28412566
TI - Removal mechanisms of benzotriazoles in duckweed Lemna minor wastewater treatment
systems.
AB - The fate of five benzotriazoles (1H-benzotriazole, BTR; 4-methyl-1H
benzotriazole, 4TTR; 5-methyl-1H-benzotriazole, 5TTR; xylytriazole, XTR and 5
chlorobenzotriazole, CBTR) was studied in batch and continuous-flow Lemna minor
systems and the role of different mechanisms on their removal was evaluated.
Single and joint toxicity experiments were initially conducted using the
Organization for Economic Co-operation and Development (OECD) protocol 221 and no
inhibition on specific growth rate of Lemna minor was observed for concentrations
up to 200MUgL-1. All tested substances were significantly removed in batch
experiments with Lemna minor. Excepting 4TTR, full elimination of CBTR, XTR, 5TTR
and BTR was observed up to the end of these experiments (36d), while the half
life values ranged between 1.6+/-0.3d (CBTR) and 25+/-3.6d (4-TTR). Calculation
of kinetic constants for hydrolysis, photodegradation, and plant uptake revealed
that for all BTRs the kinetic constants of plant uptake were by far higher
comparing to those of the other mechanisms, reaching 0.394+/-0.161d-1 for CBTR.
The operation of a continuous-flow Lemna minor system consisted of three mini
ponds and a total hydraulic residence time of 8.3d showed sufficient removal for
most target substances, ranging between 26% (4TTR) and 72% (CBTR). Application of
a model for describing micropollutants removal in the examined system showed that
plant uptake was the major mechanism governing BTRs removal in Lemna minor
systems.
PMID- 28412567
TI - Leachate treatment in landfills is a significant N2O source.
AB - The importance of methane (CH4) emissions from landfills has been extensively
documented, while the nitrous oxide (N2O) emissions from landfills are considered
negligible. In this study, three landfills were selected to measure CH4 and N2O
emissions using the static chamber method. Dongbu (DB) and Dongfu (DF) landfills,
both located in Xiamen city, Fujian Province, were classified as sanitary. The
former started to receive solid waste from Xiamen city in 2009, and the latter
was closed in 2009. Nanjing (NJ) landfill, located in Nanjing county, Fujian
Province, was classified as managed. Results showed that for the landfill
reservoirs, CH4 emissions were significant, while N2O emissions occurred mainly
in operating areas (on average, 16.3 and 19.0mgN2Om-2h-1 for DB and NJ landfills,
respectively) and made a negligible contribution to the total greenhouse gas
emissions in term of CO2 equivalent. However, significant N2O emissions were
observed in the leachate treatment systems of sanitary landfills and contributed
72.8% and 45.6% of total emissions in term of CO2 equivalent in DB and DF
landfills, respectively. The N2O emission factor (EF) of the leachate treatment
systems was in the range of 8.9-11.9% of the removed nitrogen. The total N2O
emissions from the leachate treatment systems of landfills in Xiamen city were
estimated to be as high as 8.55gN2O-Ncapita-1yr-1. These results indicated that
N2O emissions from leachate treatment systems of sanitary landfills were not
negligible and should be included in national and/or local inventories of
greenhouse gas emissions.
PMID- 28412568
TI - First report on MRSA CC398 recovered from wild boars in the north of Portugal.
Are we facing a problem?
AB - The aim of the present study was to evaluate the resistance of Staphylococcus
aureus recovered from wild boars, to analyze their genetic lineages, and to
investigate the susceptibility to oxacillin. Samples from mouth and nose of 45
wild boars (Sus scrofa) were collected during hunt activity from November 2012 to
January 2013 in the North of Portugal. S. aureus isolates were recovered from 30
of these samples (33%); one isolate/sample was further studied. The
susceptibility of the isolates was tested by disk-diffusion test against 14
antimicrobial agents and minimal inhibitory concentration was used to test
oxacillin according to EUCAST guidelines. The genetic lineages of S. aureus were
characterized by agr-typing, spa-typing and MLST. From the 30 isolates, 18 S.
aureus were susceptible to all antibiotics tested and 7 presented resistance to
one or more of the following antibiotics: penicillin (n=3), oxacillin (n=4),
cefoxitin (n=1), clindamycin (n=2), gentamicin (n=1), fusidic acid (n=1),
ciprofloxacin (n=2), tetracycline (n=1) and linezolid (n=1). One MRSA CC398 (spa
type t899) isolate was detected (oxacillin MIC=32mg/L and mecA-positive), which
presented resistance to penicillin, tetracycline, and ciprofloxacin and contained
the genes of immune evasion cluster (IEC) system (type B). The 29 methicillin
susceptible isolates were typed as ST1 (t1533), ST133 (t3583), ST1643 (t10712),
ST2328 (t3750) and the new STs (3220, 3222, 3223, 3224) associated to new spa
types t14311 and t14312. The agr-types I, II, III and IV were identified. It is a
matter of concern when MRSA and some specific lineages of S. aureus are taken as
commensal habitants of the skin and nose of wild animals and are characterized
with resistance to various antimicrobial agents in clinical use.
PMID- 28412569
TI - A comparison of the abilities of the USLE-M, RUSLE2 and WEPP to model event
erosion from bare fallow areas.
AB - Traditionally, the Universal Soil Loss Equation (USLE) and the revised version of
it (RUSLE) have been applied to predicting the long term average soil loss
produced by rainfall erosion in many parts of the world. Overtime, it has been
recognized that there is a need to predict soil losses over shorter time scales
and this has led to the development of WEPP and RUSLE2 which can be used to
predict soil losses generated by individual rainfall events. Data currently
exists that enables the RUSLE2, WEPP and the USLE-M to estimate historic soil
losses from bare fallow runoff and soil loss plots recorded in the USLE database.
Comparisons of the abilities of the USLE-M and RUSLE2 to estimate event soil
losses from bare fallow were undertaken under circumstances where both models
produced the same total soil loss as observed for sets of erosion events on 4
different plots at 4 different locations. Likewise, comparisons of the abilities
of the USLE-M and WEPP to model event soil loss from bare fallow were undertaken
for sets of erosion events on 4 plots at 4 different locations. Despite being
calibrated specifically for each plot, WEPP produced the worst estimates of event
soil loss for all the 4 plots. Generally, the USLE-M using measured runoff to
calculate the product of the runoff ratio, storm kinetic energy and the maximum
30-minute rainfall intensity produced the best estimates. As to be expected,
ability of the USLE-M to estimate event soil loss was reduced when runoff
predicted by either RUSLE2 or WEPP was used. Despite this, the USLE-M using
runoff predicted by WEPP estimated event soil loss better than WEPP. RUSLE2 also
outperformed WEPP.
PMID- 28412570
TI - Ecology: Science or philately? An interdisciplinary analysis of sustainability by
exploring if it is possible to get more and more information by reducing
collateral environmental damages.
AB - We herein explore the connections between the current condition of ecology
concerning to sustainable development and the statement of Rutherford regarding
the importance of physics to understand sustainability and biological
conservation. The recent emergence of organic biophysics of ecosystems (OBEC) may
constitute a feasible alternative to fill the gap between conventional ecological
thinking and physics, especially thermodynamics. However, our comprehension of
sustainability and biological conservation is influenced by the interactions
between information and entropy, because we tend to exclude parts of the
biosphere as well as their relationships among them. We explore the use of a
holistic analysis of sustainability and biological conservation using physics,
and also establish a parallelism between Maxwell's demons and human beings.
Lastly, the ecological meaning of the hypothetical feasibility of Maxwell's demon
at the anthroposphere scale is analyzed starting from the objections of von
Smoluchowski, Szilard and Bennet.
PMID- 28412571
TI - Thrombolytic and fibrinogenolytic properties of bioconjugate streptokinase
polyamidoamine dendrimers in vitro.
PMID- 28412572
TI - Quantitative analysis of patients with celiac disease by video capsule endoscopy:
A deep learning method.
AB - BACKGROUND: Celiac disease is one of the most common diseases in the world.
Capsule endoscopy is an alternative way to visualize the entire small intestine
without invasiveness to the patient. It is useful to characterize celiac disease,
but hours are need to manually analyze the retrospective data of a single
patient. Computer-aided quantitative analysis by a deep learning method helps in
alleviating the workload during analysis of the retrospective videos. METHOD:
Capsule endoscopy clips from 6 celiac disease patients and 5 controls were
preprocessed for training. The frames with a large field of opaque extraluminal
fluid or air bubbles were removed automatically by using a pre-selection
algorithm. Then the frames were cropped and the intensity was corrected prior to
frame rotation in the proposed new method. The GoogLeNet is trained with these
frames. Then, the clips of capsule endoscopy from 5 additional celiac disease
patients and 5 additional control patients are used for testing. The trained
GoogLeNet was able to distinguish the frames from capsule endoscopy clips of
celiac disease patients vs controls. Quantitative measurement with evaluation of
the confidence was developed to assess the severity level of pathology in the
subjects. RESULTS: Relying on the evaluation confidence, the GoogLeNet achieved
100% sensitivity and specificity for the testing set. The t-test confirmed the
evaluation confidence is significant to distinguish celiac disease patients from
controls. Furthermore, it is found that the evaluation confidence may also relate
to the severity level of small bowel mucosal lesions. CONCLUSIONS: A deep
convolutional neural network was established for quantitative measurement of the
existence and degree of pathology throughout the small intestine, which may
improve computer-aided clinical techniques to assess mucosal atrophy and other
etiologies in real-time with videocapsule endoscopy.
PMID- 28412573
TI - Patient characteristics associated with differences in radiation exposure from
pediatric abdomen-pelvis CT scans: a quantile regression analysis.
AB - BACKGROUND: Computed tomography (CT) is a widely used diagnostic tool in
pediatric medicine. However, due to concerns regarding radiation exposure, it is
essential to identify patient characteristics associated with higher radiation
burden from CT imaging, in order to more effectively target efforts towards dose
reduction. Our objective was to identify the effects of various demographic and
clinical patient characteristics on radiation exposure from single abdomen/pelvis
CT scans in children. METHODS: CT scans performed at our institution between
January 2013 and August 2015 in patients under 16 years of age were processed
using a software tool that estimates patient-specific organ and effective doses
and merges these estimates with data from the electronic health record and
billing record. Quantile regression models at the 50th, 75th, and 90th
percentiles were used to estimate the effects of patients' demographic and
clinical characteristics on effective dose. RESULTS: 2390 abdomen/pelvis CT scans
(median effective dose 1.52mSv) were included. Of all characteristics examined,
only older age, female gender, higher BMI, and whether the scan was a multiphase
exam or an exam that required repeating for movement were significant predictors
of higher effective dose at each quantile examined (all p<0.05). The effects of
obesity and multiphase or repeat scanning on effective dose were magnified in
higher dose scans. CONCLUSIONS: Older age, female gender, obesity, and multiphase
or repeat scanning are all associated with increased effective dose from
abdomen/pelvis CT. Targeted efforts to reduce dose from abdominal CT in these
groups should be undertaken.
PMID- 28412574
TI - Work place drug testing of police officers after THC exposure during large volume
cannabis seizures.
AB - Police officers responsible for the seizure and removal of illegally grown
cannabis plants from indoor and outdoor growing operations face the prospect of
THC exposure while performing their work duties. As a result, a study
investigating the amount of THC on hands and uniforms of officers during raids on
cannabis growing houses (CGHs) and forest cannabis plantations (FCPs) and in the
air at these sites was conducted. Swabs of gloves/hands, chests, and heads/necks
were collected and analysed for THC. Results of hand swabs indicated that
officers removing plants from FCPs were exposed to THC concentrations up to 20
times those involved in raids at CGHs, which was mainly associated with the
number and size of plants seized. Air samples collected inside cannabis houses
showed no detectable THC. Air samples collected inside the cargo area of the
storage trucks used during FCP raids indicated that THC can be volatilised when
lush plants are compressed by other seized plants loaded on top of them in the
truck over a period of several days, allowing composting of plants at the bottom
of the load to commence. The elevated temperature and humidity inside the truck
may assist the decarboxylation of THCA to THC, as well as increasing the rate of
volatilisation of THC. More than 100 urine samples were collected from officers
in raids on both CGHs and FCPs and all tested negative for THC. Removal of
cannabis plants by officers often resulted in cuts, abrasions and ruptured
blisters on exposed skin surfaces, particularly at FCPs. The results in this
study suggest that even when small areas of damaged skin are directly exposed to
THC by contact transfer, the likelihood of showing a positive THC urine test is
low.
PMID- 28412575
TI - The role of illicit, licit, and designer drugs in the traffic in Hungary.
AB - The aim of this study was to investigate the prevalence and pattern of
psychoactive substances among suspected DUID (Driving Under the Influence of
Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252
suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical
illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic
cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in
2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7%
(2015) of all drivers tested, based on the legal criteria of Hungary. Classical
illicit drugs were found to be present in blood or urine of 89-61%, drivers
tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21
28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in
prevalence for classical illicit drugs and a slight but statistically non
significant increase for the other three substance groups. The distribution of
drug types in each category were: [1] classical illicit drugs: cannabis (432),
amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and
clonazepam (36); [3] SDDs: pentedrone (137) and alpha-PVP (33); [4] synthetic
cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit
drug and SDD users was 30 years, while legal medications users were 36 years old
on average, and the mean age of synthetic cannabinoid users was 26.5 years. The
presence of both alcohol and at least one drug in samples was found in about 10%
of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3%
in 2015. Compared to former years the number of drivers who tested positive for
drugs doubled in Hungary, but it is still low compared to alcohol positive cases.
The relatively low detected rate of DUID can be explained by (1) combined alcohol
consumption masking drug symptoms, (2) the absence of road-side tests for illicit
and designer drugs and, (3) police officers not adequately trained to recognize
milder symptoms of impairment. Targeted education of police officers, prompt
medical examination and the use of a symptom-focused on-site survey, could
improve the efficacy of DUID investigations. Our findings are not comparable with
drug consumption habits of the general driving population. The last roadside
survey (DRUID EU-6 Project) was performed in Hungary in 2008-2009, prior to the
mass spreading of designer drugs. As their appearance has drastically changed the
pattern of drug consumption of the population, a new roadside survey, targeting
general drivers, would be necessary.
PMID- 28412576
TI - The occurrence of alcohol/drugs by toxicological examination of selected drivers
in Hong Kong.
AB - The study is to investigate the extent of alcohol/drug(s) use among selected
drivers, i.e. fatally injured drivers from traffic accidents (2006-2015), drink
driving (2006-2015) and drug driving (2010-2015) cases, in Hong Kong. Between
2006 and 2015, specimens from a total of 223 fatally injured drivers were
received for toxicological examination. Except for one driver, all other drivers
with positive findings were male. Alcohol and/or drugs were detected in 60 (27%)
cases where alcohol alone was detected in 40 cases (18%) while drugs with/without
alcohol were detected in 20 cases (9%). A decreasing trend is observed for cases
with blood/breath alcohol concentrations above the prescribed limits in both
fatally injured drivers and drivers from drink driving cases in 2006-2015. Out of
the 20 cases with positive findings in drugs, 8 of them were found with alcohol
in which only one case found at level above the prescribed limit. The frequency
of drugs encountered that are known to affect driving in blood is 31,
representing an average of about 1.7 drugs per individual. Ketamine was the most
frequently detected drug in fatally injured drivers. Sedatives/hypnotics (i.e.
diazepam/nordiazepam, midazolam, 7-aminonimetazepam, 7-aminonitrazepam and
zopiclone), morphine/monoacetylmorphine, cocaine/benzoylecgonine,
methamphetamine, methadone and codeine were also detected. There has been a sharp
increase in the submission of blood/urine specimens for toxicological analysis
related to drug driving cases since 2010 with a total of 48 cases received in
2010-2011. With the introduction of legislative amendment of drug driving law
since 2012, 154 cases were received in 2012-2015. The positive rates for drug
driving cases examined were found to be 90% (43 out of 48 cases) in 2010-2011 and
89% (137 out of 154 cases) in 2012-2015. Drivers with single drug use were more
frequently detected (40 cases in 2010-2011 and 82 cases in 2012-2015) than
multiple drug use (3 cases in 2010-2011 and 55 cases in 2012-2015) but an
increase in the use of more than one drug in driving population is noted.
Ketamine was detected in the majority of cases (34 cases in 2010-2011 and 104
cases in 2012-2015). However, drug driving cases in recent years revealed that
increase usages of methamphetamine, cocaine and zopiclone were observed. The
mean, median and range of ketamine concentrations for 134 blood samples taken
from drivers in drug driving cases were 0.34, 0.27, 0.01-1.8MUg/mL respectively.
PMID- 28412577
TI - Describing heterogeneity of unmet needs among adults with a developmental
disability: An examination of the 2012 Canadian Survey on Disability.
AB - BACKGROUND: As a signatory to the UN Convention on the Rights of Persons with
Disabilities, Canada has committed to protect the rights and dignity of persons
with developmental disabilities (DD), which means that labour markets, education,
and training opportunities should be inclusive and accessible. PURPOSE: Describe
the unmet employment, education and daily needs of adults with DD, with a sub
analysis of persons with autism spectrum disorder (ASD) and cerebral palsy (CP)
in Canada, to inform efficient and equitable policy development. METHODS AND
PROCEDURES: Secondary analysis of 2012 Canadian Survey on Disability was used to
study a sample including working age (15-64 years old) individuals with self
reported DD, CP and ASD. Persons with DD reported on their met and unmet needs in
term of activities of daily living, education and employment. OUTCOMES AND
RESULTS: Labour force participation is the lowest for those with DD compared to
any other disability. Individuals with CP and ASD report a high level of unmet
needs that differ in terms of educational, vocational and daily living supports.
CONCLUSIONS AND IMPLICATIONS: Improving labour force participation to be
inclusive and accessible requires policy that considers the range of unmet needs
that exist for persons with DD.
PMID- 28412578
TI - Communicating with scientific graphics: A descriptive inquiry into non-ideal
normativity.
AB - Scientists' graphical practices have recently become a target of inquiry in the
philosophy of science, and in the cognitive sciences. Here I supplement our
understanding of graphical practices via a case study of how researchers crafted
the graphics for scientific publication in the field of circadian biology. The
case highlights social aspects of graphical production which have gone
understudied - especially concerning the negotiation of publication. I argue that
it also supports a challenge to the claim that empirically-informed "cognitive
design principles" offer an apt understanding of the norms of success which
govern good scientific graphic design to communicate data and hypotheses to other
experts. In this respect, the case-study also illustrates how "descriptive"
studies of scientific practice can connect with normative issues in philosophy of
science, thereby addressing a central concern in recent discussions of practice
oriented philosophy of science.
PMID- 28412579
TI - Equilibrium, thermodynamic and kinetic investigations for biosorption of uranium
with green algae (Cladophora hutchinsiae).
AB - Removal of toxic chemicals from environmental samples with low-cost methods and
materials are very useful approach for especially large-scale applications. Green
algae are highly abundant biomaterials which are employed as useful biosorbents
in many studies. In the present study, an interesting type of green algae,
Cladophora hutchinsiae (C. hutchinsiae) was used for removal of highly toxic
chemical such as uranium. The pH, biosorbent concentration, contact time and
temperature were optimized as 5.0, 12 g/L, 60 min and 20 degrees C,
respectively. For the equilibrium calculations, three well known isotherm models
(Langmuir, Freundlich and Dubinin-Radushkevich) were employed. The maximum
biosorption capacity of the biosorbent was calculated as about 152 mg/g under the
optimum batch conditions. The mean energy of biosorption was calculated as 8.39
kJ/mol from the D-R biosorption isotherm. The thermodynamic and kinetic
characteristics of biosorption were also investigated to explain the nature of
the process. The kinetic data best fits the pseudo-second-order kinetic model
with a regression coefficient of >0.99 for all studied temperatures. The
calculated DeltaH degrees and DeltaG degrees values showed that the biosorption
process is exothermic and spontaneous for temperatures between 293 and 333 K.
Furthermore, after seven cycling process, the sorption and desorption
efficiencies of the biosorbent were found to be 70, and 58%, respectively meaning
that the biosorbent had sufficiently high reusability performance as a clean-up
tool.
PMID- 28412580
TI - A non-toxic dose of cobalt chloride blocks hair cells of the zebrafish lateral
line.
AB - Experiments on the flow-sensitive lateral line system of fishes have provided
important insights into the function and sensory transduction of vertebrate hair
cells. A common experimental approach has been to pharmacologically block lateral
line hair cells and measure how behavior changes. Cobalt chloride (CoCl2) blocks
the lateral line by inhibiting calcium movement through the membrane channels of
hair cells, but high concentrations can be toxic, making it unclear whether
changes in behavior are due to a blocked lateral line or poor health. Here, we
identify a non-toxic treatment of cobalt that completely blocks lateral line hair
cells. We exposed 5-day post fertilization zebrafish larvae to CoCl2
concentrations ranging from 1 to 20 mM for 15 min and measured 1) the spiking
rate of the afferent neurons contacting hair cells and 2) the larvae's health and
long-term survival. Our results show that a 15-min exposure to 5 mM CoCl2
abolishes both spontaneous and evoked afferent firing. This treatment does not
change swimming behavior, and results in >85% survival after 5 days. Weaker
treatments of CoCl2 did not eliminate afferent activity, while stronger
treatments caused close to 50% mortality. Our work provides a guideline for
future zebrafish investigations where physiological confirmation of a blocked
lateral line system is required.
PMID- 28412581
TI - Workplace violence against nurses: A cross-sectional study.
AB - BACKGROUND: Workplace violence is a serious problem for clinical nurses, as it
leads to a series of adverse consequences. However, little information is
available on the prevalence and influencing factors of workplace violence in
China. OBJECTIVES: To determine the prevalence of workplace violence against
Chinese nurses, and its influencing factors. DESIGN: A multi-center, cross
sectional study. SETTINGS: The seven geographical regions (i.e., northeast,
north, central, east, south, northwest, and southwest) of China. PARTICIPANTS:
Four thousand one hundred and twenty-five nurses. METHODS: We randomly selected
28 hospitals, located in 14 cities over 13 provinces across the seven
geographical regions. We distributed 4125 questionnaires between May 4 and
September 23, 2014. The questionnaire included demographic information, the
Workplace Violent Incident Questionnaire, the Jefferson Scale of Empathy-Health
Professionals, and the Practice Environment Scale of Nursing Work Index.
Workplace violence was assessed in terms of physical violence, non-physical
violence, sexual harassment, and organized healthcare disturbances. We then
performed descriptive analyses and logistic regressions on the collected data.
RESULTS: The response rate was 92.97% (n=3835). Additionally, we obtained valid
questionnaires from 3004 individuals. Of these, 25.77% reported experiencing
physical violence, 63.65% non-physical violence, 2.76% sexual harassment, and
11.72% organized healthcare disturbances. A logistic regression analysis revealed
that nurses who have less experience, work a rotating roster, work in emergency
rooms and pediatrics departments, have low empathy levels, and who work in poor
nursing environments have greater odds of experiencing violence. CONCLUSIONS:
Experiences of workplace violence are prevalent among Chinese nurses, and several
complex factors are associated with a greater risk of such violence, including
nurses' personal characteristics, work settings, and work environments. Our
results might help nursing managers understand their employees' work status. We
recommend that nursing leaders provide and enhance education and support for high
risk groups to help protect Chinese nurses from workplace violence.
PMID- 28412582
TI - Sex differences in neural activation following different routes of oxytocin
administration in awake adult rats.
AB - The neuropeptide oxytocin (OT) regulates social behavior in sex-specific ways
across species. OT has promising effects on alleviating social deficits in sex
biased neuropsychiatric disorders. However little is known about potential
sexually dimorphic effects of OT on brain function. Using the rat as a model
organism, we determined whether OT administered centrally or peripherally induces
sex differences in brain activation. Functional magnetic resonance imaging was
used to examine blood oxygen level-dependent (BOLD) signal intensity changes in
the brains of awake rats during the 20min following intracerebroventricular (ICV;
1MUg/5MUl) or intraperitoneal (IP; 0.1mg/kg) OT administration as compared to
baseline. ICV OT induced sex differences in BOLD activation in 26 out of 172
brain regions analyzed, with 20 regions showing a greater volume of activation in
males (most notably the nucleus accumbens and insular cortex), and 6 regions
showing a greater volume of activation in females (including the lateral and
central amygdala). IP OT also elicited sex differences in BOLD activation with a
greater volume of activation in males, but this activation was found in different
and fewer (10) brain regions compared to ICV OT. In conclusion, exogenous OT
modulates neural activation differently in male versus female rats with the
pattern and magnitude, but not the direction, of sex differences depending on the
route of administration. These findings highlight the need to include both sexes
in basic and clinical studies to fully understand the role of OT on brain
function.
PMID- 28412583
TI - Metabolic reprograming of anti-tumor immunity.
AB - Immunotherapies designed to trigger T cell destruction of tumor cells can result
in sustained and complete responses in patients whose cancers were resistant to
available treatment options. Evidence suggests that powering the T cell response
how T cells generate energy - plays an important role in their effectiveness.
Furthermore the metabolism of T cells can be modulated to improve their anti
cancer activities. In this review, we will discuss the key metabolic properties
of anti-cancer T cells, along with potential strategies to enhance immunotherapy
through the modulation of T cell metabolism.
PMID- 28412584
TI - The effects of salt concentration and foulant surface charge on hydrocarbon
fouling of a poly(vinylidene fluoride) microfiltration membrane.
AB - The effects of inorganic salts and organic hydrocarbons on membrane fouling are
often investigated independently. However, in many cases, these foulants are
commonly found together, and such mixtures are rarely the subject of fouling
studies. In this study, crude oil-in-water emulsions were formulated at three
different added NaCl concentrations, 0, 10-3 and 10-1 M. Surface properties, such
as surface tension and surface charge, of these emulsions and a poly(vinylidene
fluoride) (PVDF) microfiltration (MF) membrane were characterized. The Derjaguin
Landau-Verwey-Overbeek (DLVO) model was utilized to simulate membrane-oil droplet
and oil layer-oil droplet surface interactions. The DLVO model qualitatively
predicted increasing fouling propensity with increasing emulsion salt
concentration. The PVDF MF membrane was challenged with crude oil-in-water
emulsions in constant permeate flux crossflow fouling tests to characterize the
fouling propensity of the various emulsions, and the results were consistent with
the model predictions.
PMID- 28412585
TI - The promise of epigenetic therapy: reprogramming the cancer epigenome.
AB - Epigenetics refers to heritable molecular determinants of phenotype independent
of DNA sequence. Epigenetic features include DNA methylation, histone
modifications, non-coding RNAs, and chromatin structure. The epigenetic status of
cells plays a crucial role in determining their differentiation state and proper
function within multicellular organisms. Disruption of these processes is now
understood to be a major contributor to cancer development and progression, and
recent efforts have attempted to pharmacologically reverse such altered
epigenetics. In this mini-review we introduce the concept of epigenetic drivers
of cancer and discuss how aberrant DNA methylation, histone modifications, and
chromatin states are being targeted using drugs either in preclinical, or
clinical development, and how they fit in the context of existing therapies.
PMID- 28412586
TI - Volume-outcome relation in palliative systemic treatment of metastatic
oesophagogastric cancer.
AB - INTRODUCTION: Palliative systemic therapy has been shown to improve survival in
metastatic oesophagogastric cancer. Administration of palliative systemic therapy
in metastatic oesophagogastric cancer varies between hospitals. We aimed to
explore the association between the annual hospital volume of oesophagogastric
cancer patients and survival. METHODS: Patients diagnosed in the Netherlands
between 2005 and 2013 with metastatic oesophagogastric cancer were identified in
the Netherlands Cancer Registry. Patients were attributed according to three
definitions of high volume: (1) high-volume incidence centre, (2) high-volume
treatment centre and (3) high-volume surgical centre. Independent predictors for
administration of palliative chemotherapy were evaluated by means of
multivariable logistic regression analysis, and multivariable Cox proportional
hazard regression analysis was performed to assess the impact of high-volume
centres on survival. RESULTS: Our data set comprised 4078 patients with
metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer,
with a median overall survival of 20 weeks (95% confidence interval [CI] 19-21
weeks) and 16 weeks (95% CI 15-17 weeks), respectively. Patients with oesophageal
cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80,
95% CI 0.70-0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI
0.78-0.99) exhibited a decreased risk of death. For gastric cancer, patients
treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74-0.92) had
a superior outcome. CONCLUSION: Improved survival in patients undergoing
palliative systemic therapy for oesophagogastric cancer was associated with
treatment in high-volume treatment and surgical centres. Further research should
be implemented to explore which specific factors of high-volume centres are
associated with improved outcomes.
PMID- 28412587
TI - Accuracy of the online prognostication tools PREDICT and Adjuvant! for early
stage breast cancer patients younger than 50 years.
AB - IMPORTANCE: Online prognostication tools such as PREDICT and Adjuvant! are
increasingly used in clinical practice by oncologists to inform patients and
guide treatment decisions about adjuvant systemic therapy. However, their
validity for young breast cancer patients is debated. OBJECTIVE: To assess first,
the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality,
and second, its breast cancer-specific mortality estimates, in a large cohort of
breast cancer patients diagnosed <50 years. DESIGN: Hospital-based cohort.
SETTING: General and cancer hospitals. PARTICIPANTS: A consecutive series of 2710
patients without a prior history of cancer, diagnosed between 1990 and 2000 with
unilateral stage I-III breast cancer aged <50 years. MAIN OUTCOME MEASURES:
Calibration and discriminatory accuracy, measured with C-statistics, of estimated
10-year all-cause and breast cancer-specific mortality. RESULTS: Overall,
PREDICT's calibration for all-cause mortality was good (predicted versus
observed) meandifference: -1.1% (95%CI: -3.2%-0.9%; P = 0.28). PREDICT tended to
underestimate all-cause mortality in good prognosis subgroups (range
meandifference: -2.9% to -4.8%), overestimated all-cause mortality in poor
prognosis subgroups (range meandifference: 2.6%-9.4%) and underestimated survival
in patients < 35 by -6.6%. Overall, PREDICT overestimated breast cancer-specific
mortality by 3.2% (95%CI: 0.8%-5.6%; P = 0.007); and also overestimated it
seemingly indiscriminately in numerous subgroups (range meandifference: 3.2%
14.1%). Calibration was poor in the cohort of patients with the lowest and those
with the highest mortality probabilities. Discriminatory accuracy was moderate-to
good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the
results were similar for breast cancer-specific mortality. Adjuvant!'s
calibration and discriminatory accuracy for both all-cause and breast cancer
specific mortality were in line with PREDICT's findings. CONCLUSIONS: Although
imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality
seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings
were similar. Prognostication tools should be used with caution due to the
intrinsic variability of their estimates, and because the threshold to discuss
adjuvant systemic treatment is low. Thus, seemingly insignificant mortality
overestimations or underestimations of a few percentages can significantly impact
treatment decision-making.
PMID- 28412588
TI - Online self-test identifies women at high familial breast cancer risk in
population-based breast cancer screening without inducing anxiety or distress.
AB - INTRODUCTION: Identifying high familial breast cancer (FBC) risk improves
detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both
highly likely and potentially preventable. We assessed whether a new online self
test could identify women at high FBC risk in population-based BC screening
without inducing anxiety or distress. METHODS: After their visit for screening
mammography, women were invited by email to take an online self-test for
identifying highly increased FBC risk-based on Dutch guidelines. Exclusion
criteria were previously diagnosed as increased FBC risk or a personal history of
BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital
Anxiety Depression Scale) and BC risk perception were assessed using
questionnaires, which were completed immediately before and after taking the
online self-test and 2 weeks later. RESULTS: Of the 562 women invited by email,
406 (72%) completed the online self-test while 304 also completed questionnaires
(response rate 54%). After exclusion criteria, 287 (51%) were included for data
analysis. Median age was 56 years (range 50-74). A high or moderate FBC risk was
identified in 12 (4%) and three (1%) women, respectively. After completion of the
online self-test, anxiety and BC risk perception were decreased while distress
scores remained unchanged. Levels were below clinical relevance. Most women (85%)
would recommend the self-test; few (3%) would not. CONCLUSION: The online self
test identified previously unknown women at high FBC risk (4%), who may carry a
BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend
offering this self-test to women who attend population-based screening
mammography for the first time.
PMID- 28412589
TI - Emergency admission and survival from aggressive non-Hodgkin lymphoma: A report
from the UK's population-based Haematological Malignancy Research Network.
AB - BACKGROUND: Non-Hodgkin lymphoma (NHL) is often diagnosed after emergency
presentation, a route associated with poor survival and an indicator of
diagnostic delay. Accounting for around half of all NHLs, diffuse large B-cell
lymphoma (DLBCL) is of particular interest since although it is potentially
curable with standardised chemotherapy it can be challenging to identify at an
early stage in the primary care setting. PATIENTS AND METHODS: Set within a socio
demographically representative United Kingdom population of around 4 million
people, data are from an established patient cohort. This report includes all
patients (>=18 years) diagnosed with DLBCL 2004-2011 (n = 1660). Emergency
admissions were identified via linkage to Hospital Episode Statistics using
standard methods, and survival was examined using proportional hazards
regression. RESULTS: Two out of every five patients were diagnosed following an
emergency admission, and this was associated with advanced disease and poor
survival (p < 0.001). Among the 80% of patients treated with curative
chemotherapy, survival discrepancies emerged at the point of diagnosis; the
adjusted hazard ratio (emergency versus non-emergency) at one month being 4.0
(95% confidence interval 1.9-8.2). No lasting impact was evident in patients who
survived for 12 months or more. CONCLUSION: Emergency presentation impacts
negatively on DLBCL survival; patients presenting via this route have
significantly poorer outcomes than patients with similar clinical characteristics
who present via other routes.
PMID- 28412590
TI - Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy
in RAISE, a second-line metastatic colorectal carcinoma phase III trial.
AB - BACKGROUND: The RAISE phase III clinical trial demonstrated that ramucirumab +
(folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved
overall survival (OS) versus placebo + FOLFIRI for second-line metastatic
colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based
chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73-0.98, P = 0.022). Post hoc
analyses of RAISE patient data examined the association of carcinoembryonic
antigen (CEA) subgroups with efficacy parameters. METHODS: CEA subgroups (<=10
versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The
Kaplan-Meier method estimated the median OS and the progression-free survival
(PFS). Log-rank test compared the survival distributions within the subgroups.
Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup
interaction p-values were calculated by Cox proportional hazards model. RESULTS:
Ramucirumab treatment prolonged survival for the CEA <=10 subgroup (HR = 0.68;
95% CI = 0.50-0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76
1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater
for the CEA <=10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus
0.8 months greater, respectively). The interaction P-value between CEA level and
treatment effect on OS was 0.088. This trend was observed across randomisation
strata and to a lesser extent for PFS (P = 0.594). CONCLUSIONS: Although patients
in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab
treatment, the low baseline CEA level may identify a subgroup of patients with
mCRC who obtain greater benefit from ramucirumab.
PMID- 28412591
TI - Baseline beta-catenin, programmed death-ligand 1 expression and tumour
infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor
treated melanoma patients.
AB - BACKGROUND: The activation of oncogenic Wnt/beta-catenin pathway in melanoma
contributes to a lack of T-cell infiltration. Whether baseline beta-catenin
expression in the context of tumour-infiltrating lymphocytes (TILs) and
programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of
metastatic melanoma patients (MMPs) treated with mitogen-activated protein
kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully
clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and
paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n =
39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of beta
catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein
P3 (FOXP3) expression by immunohistochemistry, and results were correlated with
clinical outcome. Quantitative assessment of mRNA transcripts associated with
Wnt/beta-catenin pathway and immune response was performed in 51 patients.
RESULTS: We found an inverse correlation between tumoural beta-catenin expression
and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the
tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio,
OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of
CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly
associated with a higher probability of response to MAPKi monotherapy. Responding
patients showed a significantly increased expression of mRNA transcripts
associated with adaptive immunity and antigen presentation. By multivariate
analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10
0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006)
were longer in patients with high density of CD8+ T cells and beta-catenin <10%
than those without CD8+ T cells infiltration and beta-catenin >=10%. CONCLUSION:
Our findings provide evidence that in the context of MAPKi monotherapy, immune
subsets in the (TME) and gene signature predict prognosis in MMPs.
PMID- 28412592
TI - Infants' motor simulation of observed actions is modulated by the visibility of
the actor's body.
AB - Previous research suggests that 9-month-old infants will develop a response bias
in the A-not-B search paradigm after only observing an experimenter search for a
hidden object on A-trials. In the current experiment, we tested whether infants
would persist in making errors when only the hands-and-arms of the experimenter
were visible. Three different conditions were included: (1) the experimenter was
silent while hiding and finding the object, (2) the experimenter communicated
with the infant via infant-directed speech, or (3) the body of the experimenter
was visible during the training phase before his head and body were occluded
during the test phase. Unlike previous studies, the results revealed that a
significant proportion of infants searched correctly when the body of the
experimenter was not visible, and only the combination of infant-directed speech
and familiarization with a fully-specified body resulted in a majority of infants
committing search errors. These results are interpreted as suggesting that the
likelihood of infants committing search errors is dependent on their motor
simulation of the experimenter's reaching. The strength of this simulation is
graded by the similarity between the observed action and the motor
representation.
PMID- 28412593
TI - Bootstrapping language acquisition.
AB - The semantic bootstrapping hypothesis proposes that children acquire their native
language through exposure to sentences of the language paired with structured
representations of their meaning, whose component substructures can be associated
with words and syntactic structures used to express these concepts. The child's
task is then to learn a language-specific grammar and lexicon based on (probably
contextually ambiguous, possibly somewhat noisy) pairs of sentences and their
meaning representations (logical forms). Starting from these assumptions, we
develop a Bayesian probabilistic account of semantically bootstrapped first
language acquisition in the child, based on techniques from computational parsing
and interpretation of unrestricted text. Our learner jointly models (a) word
learning: the mapping between components of the given sentential meaning and
lexical words (or phrases) of the language, and (b) syntax learning: the
projection of lexical elements onto sentences by universal construction-free
syntactic rules. Using an incremental learning algorithm, we apply the model to a
dataset of real syntactically complex child-directed utterances and (pseudo)
logical forms, the latter including contextually plausible but irrelevant
distractors. Taking the Eve section of the CHILDES corpus as input, the model
simulates several well-documented phenomena from the developmental literature. In
particular, the model exhibits syntactic bootstrapping effects (in which
previously learned constructions facilitate the learning of novel words), sudden
jumps in learning without explicit parameter setting, acceleration of word
learning (the "vocabulary spurt"), an initial bias favoring the learning of nouns
over verbs, and one-shot learning of words and their meanings. The learner thus
demonstrates how statistical learning over structured representations can provide
a unified account for these seemingly disparate phenomena.
PMID- 28412594
TI - Synthesis and revised stereochemical assignment of C-allyl glucopyranosides and
derivatives.
AB - alpha- and beta-C-allylglucopyranosides and hydroxy-, bromo- and azido
derivatives were prepared through allylation at C-1 of methyl 2,3,4,6-tetra-O
benzyl-D-glucopyranoside or 1-O-acetyl-2,3,4,6-tetra-O-benzyl-D-glucopyranose and
subsequent chemical modifications of the alkene on the anomeric arm. However, we
picked out some discordance between some recent published studies and our
results. After a thorough work of characterization and NMR analysis, we
unambiguously confirmed alpha and beta stereochemistry of the two series of
compounds and fully described for the first time beta-C-propyl alcohol, bromide
and azide of 2,3,4,6-tetra-O-benzyl-D-glucopyranose.
PMID- 28412595
TI - Health-risk behaviour among residents in deprived neighbourhoods compared with
those of the general population in Denmark: A cross-sectional study.
AB - This study compares health-risk behaviours (including the co-occurrence of health
risk behaviours) of residents in the deprived neighbourhoods with those of the
general population of Denmark. It also examines associations between
sociodemographic and socioeconomic characteristics and health-risk behaviours in
deprived neighbourhoods in Denmark. Even after adjustment for socioeconomic
characteristics there were large differences in health-risk behaviours between
residents in deprived neighbourhoods and the general population. In the deprived
neighbourhoods large sociodemographic and socioeconomic differences in health
risk behaviours were found among the residents. Our findings highlight the need
for health promotion programmes targeting residents in deprived neighbourhoods.
PMID- 28412596
TI - Is lenticulostriated vasculopathy an unfavorable prognostic finding in infants
with congenital cytomegalovirus infection?
AB - BACKGROUND: Lenticulostriated vasculopathy (LSV) detected in head ultrasound
(HUS) has been related to neurological and hearing sequelae in infants with
congenital cytomegalovirus (cCMV) infection. OBJECTIVE: To assess the role of LSV
in predicting neurodevelopmental and hearing outcomes in infants with cCMV
infection. STUDY DESIGN: We enrolled consecutive infants who were affected by
cCMV infection and underwent HUS within the first month of life. Data on clinical
onset and course, laboratory findings, visual/hearing functions and
neurodevelopmental outcome were collected. As controls, infants with suspected
intrauterine exposure to Toxoplasma and with no confirmed congenital
toxoplasmosis were considered. RESULTS: Data from 161 infants with cCMV infection
(105 symptomatic) and 133 controls were analyzed. HUS was normal in 66 (41%) cCMV
patients. Among these, 28 (42.4%) were symptomatic and 38 (57.6%) asymptomatic
infants. The percentage of patients with no HUS abnormalities was higher in
asymptomatic (38/56, 67.9%) than in symptomatic infants (28/105, 26.7%) (p<0.05).
LSV, as isolated or associated with other brain abnormalities, was diagnosed in
64/161 (39.7%) patients with cCMV compared to 24/133 (18%) controls (p<0.05). In
cCMV group, LSV was found in 51 (48.6%) symptomatic infants and in 13 (72.2%)
asymptomatic patients (p>0.05). Overall, in the whole population of 95 patients
with cCMV and abnormal HUS results, LSV (alone or with other findings) did not
represent a risk factor for unfavorable neurological and hearing outcome. Similar
results were obtained when we limited the analysis to the group of symptomatic
cCMV patients. CONCLUSIONS: Although LSV is a common HUS finding in infants with
cCMV infection, its presence is not predictive of an adverse outcome. Our data
suggest that HUS as a single neuroimaging investigation is unreliable in
selecting candidates to antiviral therapy, mainly in presence of LSV as isolated
finding.
PMID- 28412597
TI - Peptide blockers of Kv1.3 channels in T cells as therapeutics for autoimmune
disease.
AB - The voltage-gated Kv1.3 channel in T lymphocytes is a validated therapeutic
target for diverse autoimmune diseases. Here we review the discovery of Kv1.3,
its physiological role in T cells, and why it is an attractive target for
modulating autoimmune responses. We focus on peptide inhibitors because the first
Kv1.3-selective inhibitor in human trials is a peptide derived from a marine
organism. Two broad classes of peptides block Kv1.3, the first from scorpions and
the second from sea anemones. We describe their structures, their binding site in
the external vestibule of Kv1.3, how they have been engineered to improve Kv1.3
specificity, and their pharmacokinetic and pharmacodynamic properties. Finally,
we highlight the therapeutic potential of Kv1.3 peptide inhibitors to treat
autoimmune diseases without compromising protective immune responses.
PMID- 28412598
TI - Effect of two isolated vocal facilitating techniques glottal fry and yawn-sigh on
the phonation of female speech-language pathology students: A pilot study.
AB - OBJECTIVE: The purpose of this study was to determine the effect of two isolated
vocal facilitating techniques, glottal fry and yawn-sigh, on the phonation of
vocally healthy female speech-language pathology (SLP) students. STUDY DESIGN: A
multigroup pretest-posttest design was used. METHODS: A group of thirty-six
healthy female SLP students with a mean age of 18.1 years were assigned into
three groups: a glottal fry group (practicing the facilitating technique glottal
fry across 18 weeks, n=12), a yawn-sigh group (practicing the facilitating
technique yawn-sigh across 18 weeks, n=12) and a control group (receiving no
facilitating techniques, n=12). To compare vocal measures before and after this
training period, an identical objective voice assessment protocol (maximum
performance task, acoustic analysis, voice range profile and Dysphonia Severity
Index) was performed in the three groups. Groups were compared over time using
linear mixed models. Within-group effects of time were determined using post hoc
pairwise comparisons. RESULTS: Glottal fry resulted in a significant decrease in
lowest and highest intensity. Yawn-sigh resulted in a significant increase in
fundamental frequency, a significant decrease in shimmer and noise-to-harmonic
ratio, and a significant increase in highest intensity. CONCLUSIONS: Yawn-sigh
may have a positive effect on the phonation of female vocally healthy future
SLPs, whereas results are less supportive for using glottal fry in training this
population's voice.
PMID- 28412599
TI - Group intervention for individuals with primary progressive aphasia and their
spouses: Who comes first?
AB - Primary progressive aphasia (PPA) is a neurodegenerative dementia in which
language impairment is the first and most dominant symptom. There is a
considerable dearth of interventions for PPA although language rehabilitation has
made headway in managing the disorder. Thus far, no comprehensive services have
been proposed for PPA clients and/or their spouses. This paper describes the
first structured group intervention program designated exclusively for people
with PPA and their caregivers. This pilot project originates from a clinical
service and presents supporting evidence for initiation of a larger study to
establish an evidence-based intervention for PPA. A 10-week intervention program
comprised working on language activities, learning communication strategies,
counselling and education. Outcome measures administered to participants and
their spouses before and after the intervention were compared showed improvements
in quality of communication and coping skills in the PPA group compared to
controls. Qualitative comments from all 10 participants in the active treatment
group highlighted the necessity of intervention that is tailored specifically to
the PPA population and addresses the needs of both individuals with PPA and their
caregivers. All participants in the intervention group contributed to the study
and are also co-authors of this paper.
PMID- 28412600
TI - DNA methylation changes at TREM2 intron 1 and TREM2 mRNA expression in patients
with Alzheimer's disease.
AB - OBJECTIVES: Recent genome-wide association studies revealed that Triggering
receptor expressed on myeloid cells 2 (TREM2) was associated with Alzheimer's
disease (AD) and other neurodegenerative diseases. We previously reported that
TREM2 mRNA is highly expressed in leukocytes of AD patients compared to those in
healthy controls. However, the mechanism of TREM2 expression change is still not
known. In this study, we examined the involvement of the DNA methylation status
of TREM2 in its high gene expression. MATERIALS AND METHODS: Fifty AD subjects
and age- and sex-matched control subjects were recruited (25 males, 25 females;
79.9 +/- 5.27 and 79.4 +/- 3.92 years old, respectively). TREM2 mRNA expression
and the percentage of DNA methylation at four CpG sites in intron 1 of TREM2 were
studied using their peripheral leukocytes. RESULTS: We confirmed that TREM2 mRNA
expression in leukocytes was significantly higher in AD patients than in controls
(p = 0.007). The percentage methylation at three CpG sites in TREM2 intron 1 was
significantly lower in AD subjects than in control: CpG1, 9.4 +/- 3.2 vs 11.9 +/-
4.0 (p = 0.001); CpG2, 15.4 +/- 4.9 vs 19.1 +/- 4.8 (p = 0.001); CpG3, 20.8 +/-
5.5 vs 25.5 +/- 5.4 (p < 0.001); and the average percentage methylation of all
CpG sites: 13.5 +/- 3.7 vs 16.1 +/- 3.8 (p = 0.002), respectively. In addition,
there were significant negative correlations between TREM2 mRNA expression and
the percentage DNA methylation of each of CpG sites (CpG1, r = -0.416, p < 0.001;
CpG2, r = -0.510, p < 0.001; CpG3, r = -0.504, p < 0.001; CpG4, r = -0.356, p <
0.001). CONCLUSIONS: Lower DNA methylation at TREM2 intron 1 caused higher TREM2
mRNA expression in the leukocytes of AD subjects versus controls and may be a
biomarker for AD.
PMID- 28412601
TI - A systematic review of factors associated with service user satisfaction with
psychiatric inpatient services.
AB - BACKGROUND: Satisfaction is seen as an indicator of the quality of mental health
services and has been related to outcomes and compliance with treatment. The
current review seeks to examine the factors relating to satisfaction with
inpatient services. METHOD: A search was conducted of PsycInfo, Web of Science,
Cinahl, Embase and Medline databases. Screening resulted in 32 papers being
included in the review. Papers were subject to quality assessment using the Mixed
Methods Appraisal Tool (MMAT). RESULTS: Review of the included papers suggested
factors relating to satisfaction could be broadly classified as either service
user or service/ward related. Service user related factors included findings that
satisfaction was higher when service users were admitted voluntarily. Service
related factors included findings that satisfaction was negatively associated
with experiences of coercion and positively associated with being on an open
ward. CONCLUSION: It appears that coercion has a key role in ratings of
satisfaction. Additionally, service users reported an impact of staff
relationships, and the ward environment. Satisfaction is associated with a range
of factors, an awareness of which will allow for the development of quality
services that meet the needs of service users.
PMID- 28412602
TI - Secondary outcomes from the pediatric obsessive compulsive disorder treatment
study II.
AB - : The Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II)
investigated the benefit of serotonin reuptake inhibitor (SRI) augmentation with
cognitive behavioral therapy (CBT). Primary outcomes focused on OCD symptom
change and indicated benefit associated with a full course of CBT. Given that the
majority of youth with OCD suffer from significant comorbid symptoms and impaired
quality of life, the current study examined POTS II data for effects on secondary
outcomes. Participants were 124 youth ages 7-17 years with a primary diagnosis of
OCD who were partial responders to an adequate SRI trial. Participants were
randomized to medication management, medication management plus instructions in
cognitive behavioral therapy (CBT), or medication management plus full CBT. Acute
effects on non-OCD anxiety, depression, inattention, hyperactivity, and quality
of life were examined across treatment conditions. Improvement across treatment
was observed for non-OCD anxiety, inattention, hyperactivity, and quality of
life. Changes were generally significantly greater in the group receiving full
CBT. Child-rated depression was not found to change. OCD-focused treatment lead
to improvement in other areas of psychopathology and functioning. For youth who
are partial responders to SRI monotherapy, augmentation with full CBT may yield
the greatest benefit on these secondary outcomes. CLINICAL TRIALS REGISTRATION:
Treatment of Pediatric OCD for SRI Partial Responders, Clinicaltrials.gov
Identifier: NCT00074815, http://clinicaltrials.gov/show/NCT00074815.
PMID- 28412603
TI - Impairments of balance, stepping reactions and gait in people with cervical
dystonia.
AB - BACKGROUND: Impaired balance is common in neurological disorders. Cervical
dystonia is a neurological movement disorder affecting the neck. The effect of
this aberrant head posture on physical function is unknown. OBJECTIVES: To
compare balance, mobility, gait and stepping reactions between ten people with
cervical dystonia and ten control adults. METHODS: Spatiotemporal gait parameters
and walking speed were assessed using a computerised walkway. Step length and
time, time in double support and gait variability were calculated, then
normalised to gait speed. Centre of pressure path length was assessed with eyes
open and eyes closed to calculate a Romberg Quotient. Simple and choice reaction
times were measured using customised apparatus while mobility was assessed by the
timed up and go. Cervical spine range of motion was measured using a head mounted
goniometer. Self-reported scales included Falls Self Efficacy Scale and Dystonia
Discomfort Scale. RESULTS: There was a difference between groups for most outcome
measures. The timed up-and-go and walking speed was slower (both P<0.005) and the
Romberg Quotient lower (P=0.046) in cervical dystonia. People with cervical
dystonia had lower falls self-efficacy (P=0.0002). Reduced cervical range of
motion was correlated with balance, stepping reaction time and mobility (all
P<0.05). Timed up and go was positively associated with stepping reaction time
(P<0.01). Dystonia discomfort did not impact function. CONCLUSIONS: People with
cervical dystonia displayed deficits in balance, gait and stepping reactions, and
expressed higher fear of falling. Studies to further elucidate functional
limitations and their impact on activity and participation in daily life are
required.
PMID- 28412604
TI - Highlighting the differential role of leaf paraheliotropism in two Mediterranean
Cistus species under drought stress and well-watered conditions.
AB - The differential degree by which paraheliotropism may counterbalance the
deleterious impact of high irradiance between congeneric species in relation to
different water availabilities has been poorly investigated. We followed the
evolution of gas exchange, quenching analysis and OJIP parameters in restrained
(R) and free (F) to move leaves of Cistus monspeliensis (CM) and Cistus
salvifolius (CS) under drought stress (WS) and well-watered conditions (WW).
Concerning gas exchange parameters, leaf restriction effect was overall not
significant in CM except in apparent carboxylation efficiency (Ce) under WS,
while CS showed a significant sensitivity of maximum net photosynthetic rate
(Amax), stomatal conductance (gs) and Ce even under WW. The recovery analysis
highlighted also a faster gs recovery in F leaves. Furthermore, in both the
species, restriction affected photon allocation pathways especially in terms of
light-regulated and light-independent constitutive non-photochemical energy
dissipation under WW, ultimately affecting electron transport rate (ETR).
Nevertheless, the OJIP analysis provided us evidences that CM was characterized
by a down-regulation of ETR while an impairment occurs in CS. In CM this was due
to its ability to modify a certain fraction of reaction centers thus resulting in
a higher capability for dissipation of excess light energy under well-watered
conditions, not affecting electron transport efficiency. This response was not
observed in CS. Overall, we demonstrated that congeneric species, even mostly
sharing the same physiological targets, differ in the degree by which leaf
movements help to counterbalance the negative effect of the high irradiance in
relation with the amount of water available.
PMID- 28412605
TI - Brachytic 1 of barley (Hordeum vulgare L.) encodes the alpha subunit of
heterotrimeric G protein.
AB - Physiological and molecular biological analysis of the dwarf barley (Hordeum
vulgare L.) mutant brachytic 1 (brh1) was conducted. The root responses of brh1
to brassinolide were weaker than those of wild type, but the responses of leaf
segments of dark-grown plants were not. Responses of brh1 to gibberellin A3 were
similar to or slightly stronger than those of wild type. Endogenous levels of
these hormones in young seedlings were not clearly different between brh1 and
wild type. Skotomorphogeneses of brh1 were similar to those of wild type. Some of
these physiological characteristics of brh1 resemble those of the dwarf rice
(Oryza sativa L.) mutant daikoku (dwarf1; d1), whose dwarfism is caused by a
mutation in the heterotrimeric G protein alpha (Galpha) subunit. A database
search indicated that the barley Galpha gene is located near the locus where Brh1
has already been genetically mapped. Sequences of the Galpha gene and cDNAs of
five brh1 alleles contained substitutions and a deletion that lead to the
production of abnormal Galpha proteins. These results indicate that the phenotype
of brh1, similarly to that of d1, is caused by mutations in an orthologous gene
encoding Galpha.
PMID- 28412606
TI - Quantification of alprenolol and propranolol in human plasma using a two
dimensional liquid chromatography (2D-LC).
AB - A new two-dimensional liquid chromatography (2D-LC) method using a column
switching valve, with a restricted-access media (RAM) column in the first
dimension was developed and validated for the quantification of two beta-blockers
in human plasma. Several parameters, such as sample collection, mobile phase
composition and flow rate for sample cleanup, transference and analytical
separation of the beta-blockers were investigated and optimized. The developed
method allowed for the simultaneous pre-treatment and quantification of
alprenolol (ALP) and propranolol (PRO) in human plasma in less than 25min. The
method consisted in the injection of 100MUL of plasma samples on the RAM alkyl
diol-silica column (Lichrospher(r) RP-18 ADS, 25MUm) with water/acetonitrile
(98:2, v/v; at a flow rate of 2.0mL/min) and then transferred (via a six-port
valve) to the analytical column (Luna PFP (2), 150*4.6mm ID, 100A, 3MUm) with
0.1% (v/v) triethylamine in water acidified with trifluoroacetic acid
(pH=3)/acetonitrile (74:26, v/v) at a flow rate of 0.6mL/min in a back-flush
mode. The column oven temperature was optimized to 42 degrees C and the
fluorescence detector set at 280nm and 310nm (excitation and emission,
respectively). The method was validated according to the European Medicines
Agency's guidelines and was linear (r2>0.999) over a dynamic range of 5.0 -
200ng/mL. Recoveries ranged from 90.2 and 107% and the lower limit of
quantification was 5.0ng/mL for both compounds. Precision was expressed as a
percentage of relative standard deviation and did not exceed 11%. Finally, the
method was successfully applied to determine the plasma concentration of PRO in
four healthy volunteers.
PMID- 28412607
TI - Effect of early postnatal exposure to valproate on neurobehavioral development
and regional BDNF expression in two strains of mice.
AB - Valproate has been used for over 30years as a first-line treatment for epilepsy.
In recent years, prenatal exposure to valproate has been associated with
teratogenic effects, limiting its use in women that are pregnant or of
childbearing age. However, despite its potential detrimental effects on
development, valproate continues to be prescribed at high rates in pediatric
populations in some countries. Animal models allow us to test hypotheses
regarding the potential effects of postnatal valproate exposure on
neurobehavioral development, as well as identify potential mechanisms mediating
observed effects. Here, we tested the effect of early postnatal (P4-P11)
valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in
two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early
valproate exposure on regional BDNF protein levels, a potential target of
valproate, and mediator of neurodevelopmental outcomes. We found that early life
valproate exposure led to significant motor impairments in both SVE129 and
C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as
well as impairments in the righting reflex (P7-8), wire hang (P17), open field
(P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early
locomotor effects were strain- and dose-dependent. We observed no effects of
valproate on early markers of anxiety-like behavior. Importantly, early life
valproate exposure had significant effects on regional BDNF expression, leading
to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice,
while not impacting hippocampal BDNF protein levels. These observations indicate
that postnatal exposure to valproate may have significant, and region-specific
effects, on neural and behavioral development, with specific consequences for
cerebellar development and motor function.
PMID- 28412609
TI - Dexamethasone promotes regeneration of crushed inferior alveolar nerve by
inhibiting NF-kappaB activation in adult rats.
AB - PURPOSE: Nuclear factor kappa B (NF-kappaB), which is closely related to
inflammation, has become a topic of interest for research. The aim of this study
is to investigate the effects of dexamethasone (Dex), an inhibitor of NF-kappaB,
on inferior alveolar nerve injury in adult rats. MATERIALS AND METHODS: The
crushed inferior alveolar model is established in Wistar rats and they are
randomly divided into three groups according to treatment: pyrrolidine
dithiocarbamate (PDTC), dexamethasone (Dex), and saline (physiological saline).
After treatment, the rats are respectively sacrificed at 3, 7, and 14d, and
inferior alveolar nerves are extracted for histochemical and western blot
analysis. RESULT: Compared with the PDTC and saline groups, nerve fibers in the
Dex group are regularly arranged with few vacuoles, which is similar to normal
inferior alveolar nerves. Immunofluorescent results show significantly decreased
NF-kappaB expression in the Dex group. Western bolt shows higher expression of
GAP-43 and lower expression of NF-kappaB. CONCLUSION: Taken together, all results
show that dexamethasone significantly improved the regeneration of crushed
inferior alveolar nerves by inhibiting NF-kappaB activation in adult rats.
PMID- 28412608
TI - DSM-5 criteria for PTSD in parents of pediatric patients with epilepsy: What are
the changes with respect to DSM-IV-TR?
AB - Increasing literature suggests the need to explore for post-traumatic stress
disorder (PTSD) and post-traumatic stress symptoms in parents and caregivers of
children with acute and chronic illnesses but scant data are available on
epilepsy. The aim of the present study was to estimate full and partial PTSD
rates among parents of children with epilepsy comparing DSM-5 and DSM-IV-TR
criteria. Further, the aim of the present study was to examine possible gender
differences between mothers and fathers. Results showed 9.1% and 12.1% PTSD rates
in the total sample, according to DSM-5 or DSM-IV-TR criteria, respectively, with
an overall consistency of 92.9% (Kohen's K=0.628, p=.453). Significant gender
differences emerged for Avoidance/Numbing and Hyperarousal symptoms diagnosed by
means of DSM-IV-TR criteria, as well as for Negative alterations in
cognitions/mood and Hyperarousal symptoms, when adopting DSM-5 criteria. This
study underscores the relevance of detecting PTSD in parents of children with a
chronic illness such as epilepsy.
PMID- 28412610
TI - Overexpression and varied clinical significance of Th9 versus Th17 cells in
distinct subtypes of oral lichen planus.
AB - OBJECTIVE: Oral lichen planus (OLP) presents with large numbers of T lymphocytes
accumulating beneath the epithelium of the oral mucosa; however, its aetiology
remains obscure. A potential role for an emerging novel T cell subset, Th9, in
OLP has recently been suggested but remains to be clarified. The current aim was
to investigate the expression and potential clinical significance of Th9 cells in
distinct subtypes of OLP. MATERIALS AND METHODS: Peripheral blood samples were
collected from 41 OLP patients and 18 healthy controls (HCs). Flow cytometric
analysis was used to detect the CD4+ T helper subset Th9 (IL-9+IL-17-CD4+ Th
cells) and Th17 (IL-9-IL-17+CD4+ Th cells) expression levels. RESULTS: Flow
cytometry results showed significantly elevated levels of Th9 cells in reticular
and erosive OLP compared to HCs. Th9 expression in erosive OLP was less than in
reticular OLP, indicating that Th9 but not Th17 cells may play a predominant role
in reticular disease. However, in erosive OLP patients, we found much higher
levels of Th17 cells compared to reticular OLP patients and HCs, indicating that
Th17 dominates in erosive OLP. Statistical analysis showed positive correlations
of Th9 cells and Th17 cells in patients with reticular or erosive OLP but none in
HCs. CONCLUSIONS: Th9 and Th17 cells may take the predominant roles in reticular
and erosive OLP respectively, and their numbers were positively correlated in
reticular and erosive OLP patients. Elevated circulating Th9 cells may help
maintain immune balance in OLP immunopathogenesis, which requires further
investigation.
PMID- 28412611
TI - Hypermethylation of Death-Associated Protein Kinase (DAPK1) and its association
with oral carcinogenesis - An experimental and meta-analysis study.
AB - OBJECTIVES: The value of abnormal DNA methylation of DAPK1 promoter and its
association with various cancers have been suggested in the literature. To
establish the significance of DNA methylation of DAPK1 promoter in oral squamous
cell carcinoma (OSCC), we a) performed a case-control study, b) evaluated
published data for its utility in the diagnosis and prognosis of OSCC and c)
identified the association of DAPK1 gene expression with promoter DNA methylation
status. DESIGN: Bisulfite gene sequencing of DAPK1 promoter region was performed
on non-malignant and malignant oral samples. Further, using a systematic search,
330 publications were retrieved from PubMed, Scopus, and Google Scholar and 11
relevant articles were identified. RESULTS: Significant association of DAPK1
promoter methylation with OSCC (p<0.0001) was observed in the case-control study.
The studies chosen for meta-analysis showed prognostic and predictive
significance of DAPK1 gene promoter, despite defined inconsistencies in few
studies. Overall, we obtained a statistically significant (p-value<0.001)
association for both sensitivity and specificity of DAPK1 DNA promoter
methylation in oral cancer cases, without publication bias. CONCLUSION: DNA
hypermethylation of DAPK1 gene promoter is a promising biomarker for OSCC
prediction/prognostics and suggests further validation in large distinct cohorts
to facilitate translation to clinics.
PMID- 28412612
TI - Impairment in Social Functioning differentiates youth meeting Ultra-High Risk for
psychosis criteria from other mental health help-seekers: A validation of the
Italian version of the Global Functioning: Social and Global Functioning: Role
scales.
AB - Social and occupational impairments are present in the schizophrenia prodrome,
and poor social functioning predicts transition to psychosis in Ultra-High Risk
(UHR) individuals. We aimed to: 1) validate the Italian version of the Global
Functioning: Social (GF: S) and Global Functioning: Role (GF: S) scales; 2)
evaluate their association with UHR criteria. Participants were 12-21-years-old
(age, mean=15.2, standard deviation=2.1, male/female ratio=117/120) nonpsychotic
help-seekers, meeting (N=39) or not (N=198) UHR criteria. Inter-rater reliability
was excellent for both scales, which also showed good to excellent concurrent
validity, as measured by correlation with Global Assessment of Functioning (GAF)
scores. Furthermore, GF:S and GF: R were able to discriminate between UHRs and
non-UHRs, with UHRs having lower current scores. After adjusting for current GAF
scores, only current GF:S scores independently differentiated UHR from non-UHR
(OR=1.33, 95%CI: 1.02-1.75, p=0.033). Finally, UHR participants showed a steeper
decrease from highest GF:S and GF: R scores in the past year to their respective
current scores, but not from highest past year GAF scores to current scores.
GF:S/GS: R scores were not affected by age or sex. GF:S/GF: R are useful
functional level and outcome measures, having the advantage over the GAF to not
confound functioning with symptom severity. Additionally, the GF:S may be helpful
in identifying UHR individuals.
PMID- 28412613
TI - Intensified emotion perception in depression: Differences in physiological
arousal and subjective perceptions.
AB - People suffering from depression perceive themselves and their surroundings as
more negative than healthy ones. An explanation might be that depressed
individuals experience negative information as more stressful than non-depressed
subjects and, consequently, respond in an amplified manner on a subjective and
physiological level. To test this proposition, we presented 41 patients with
recurrent depressive episodes and 42 controls with stimuli from the International
Affective Picture System split into three valence categories while different
parameters of physiological arousal (e.g., heart rate variability) and subjective
perceptions of valence and arousal were assessed. Furthermore, we examined social
skills and emotional competence. Results regarding physiological arousal revealed
an elevated skin temperature and a more accentuated respiratory frequency in
depressed subjects. Furthermore, depressed subjects rated the stimuli as more
negative and arousing, which was associated with reduced social and emotional
competence. Variation in antidepressant medication, menstrual cycle and other
factors that have an impact on HRV are a potential bias. Our findings suggest an
intensified perception of negative emotion in depressed individuals as compared
to controls that manifests itself in an increased physiological arousal as well
as on a subjective level. This intensified emotion perception is further
associated with deficits in social and emotional competence.
PMID- 28412614
TI - Pain and multiple facets of anger and hostility in a sample seeking treatment for
problematic anger.
AB - A number of studies have reported associations between pain and anger in samples
with chronic pain, but research has mostly overlooked associations between pain
and anger in those with problematic anger. The present study explored
associations between pain severity and a variety of anger and hostility
constructs in a sample seeking anger treatment (n =131). Zero-order correlations
and partial correlations were used to examine associations between pain, anger,
and hostility, controlling for depressive symptoms. Hierarchical regression
models examined potential interaction effects of gender on associations between
pain and these outcomes. Pain severity was positively associated with trait
anger, outward anger expression, hostile interpretation bias, hostile ideation,
and inability to forgive others. These associations were independent of co
occurring depressive symptoms, with some exceptions. Gender moderated the
association between pain and hostile ideation such that pain was positively
associated with hostile ideation in women but not men. Pain severity was uniquely
associated with multiple outcomes of relevance to individuals undergoing
treatment for problematic anger. Clinical implications will be discussed.
PMID- 28412615
TI - Suicide risk among young children after the Great East Japan Earthquake: A follow
up study.
AB - On 11 March 2011, the Great East Japan Earthquake and subsequent tsunami hit East
Japan. We aim to investigate the impact of trauma experiences related to the
earthquake on suicide risk among young children, stratified by child sex.
Participants at baseline were children who were exposed to the 2011 disaster at
preschool age (affected area, n=198; unaffected area, n=82, total n=280). From
July 2013 to May 2014, suicide risk was assessed using the Mini International
Neuropsychiatric Interview for Children and Adolescents (MINI-KID) in a follow-up
interview conducted by a child psychiatrist or psychologist (N=210, follow-up
rate: 75%). Among young girls in the affected area, 12 out of 65 (18.5%) showed
suicidal ideation, which is significantly higher than girls in the unaffected
area (4.7%, p for chi-square=0.036). In the multivariate model adjusted for
potential confounders and mediators, the odds ratio for 4 or more trauma
experiences related to the earthquake was 5.74 (95% confidence interval: 0.83
39.6, p=0.076) compared to no trauma experience related to the earthquake. Among
young boys, trauma exposure was not associated with suicidal ideation. Our
findings showed that young girls who experienced earthquake-related trauma at
preschool age had a higher suicidal ideation 3 years after the earthquake.
PMID- 28412616
TI - Measuring fluctuations across the Continuum of Auditory Hallucinations.
Development and validation of a state inventory.
AB - In order to identify causes and triggers of hallucinations that can inform
therapy, reliable, valid, and change-sensitive instruments to assess
hallucinatory experiences in the subclinical and clinical range are needed. We
developed and validated a novel scale, the Continuum of Auditory Hallucinations -
State Assessment (CAHSA), to be used for repeated assessment of the subclinical
factors vivid imagination, intrusive thoughts, and perceptual sensitivity as well
as auditory hallucinations. After selecting items for the four factors in a first
test sample (n=84), we tested factorial validity using CFA and criterion validity
with self-reported psychosis-like experiences (n=534). Finally, within-subject
variation of CAHSA scores over 14 days and time-lagged associations between its
factors were explored (n=85). A 9-item CAHSA was selected that showed good
factorial validity, criterion validity, and substantial, valid within-subject
variation. Time-lagged regression showed that vivid imagination, perceptual
sensitivity, and intrusive thought precede auditory hallucinations. In sum, the
CAHSA validly measures fluctuation along the continuum of auditory
hallucinations, is sensitive to change, and well suited for experimental studies,
repeated measurement, and longitudinal research.
PMID- 28412617
TI - Selection of optimized air pollutant filtration technologies for petrochemical
industries through multiple-attribute decision-making.
AB - Selecting cost-effective and efficient air filtration technologies that ensure
sustainable development is a challenge to national, regional and local policy
makers. Various factors such as efficiency, maintainability, and design of the
developed devices can affect the selection of optimized technologies. The present
study aimed to select optimal technologies for air filtration devices in
petrochemical industries through a multi-criteria decision-making (MADM) method
based on a fuzzy model of Technique for Order of Preference by Similarity to
Ideal Solution (TOPSIS). Five criteria (filtration efficiency, cost,
maintainability, designability, and size) were used to rank air pollution control
technologies designed to eliminate particulate matter (PM), volatile organic
compounds (VOCs), and ammonia (NH3). According to the results, the research
criteria had different weights for different air pollutants. High-efficiency
particulate air (HEPA + pre collector) filters, plasma chemistry, and chemical
absorption were identified as the most appropriate filtration methods for PM,
VOCs, and NH3, respectively (coefficients = 0.923, 0.9586, and 0.867,
respectively).
PMID- 28412618
TI - Untapped potentials of acrylonitrile-butadiene-styrene/polyurethane (ABS/PU)
blend membrane to purify dye wastewater.
AB - Production of acrylonitrile-butadiene-styrene/polyurethane (ABS/PU) blend
membrane with high rejection efficiency for disperse and vat dyes, is introduced
as a facile and cost effective technique to purify textile wastewater. In this
respect, membranes are produced using commercially available polymers, i.e. ABS
and PU, with different compositions (ABS/PU: 100/0, 80/20, 70/30, 60/40 and 50/50
w/w) through wet casting. Casting solutions with concentration of 30 wt% are
prepared using two different solvents, i.e. dimethylformamide (DMF) and N-methyl
2- pyrrolidone (NMP). The prepared membranes are characterized using a variety of
analytical techniques including SEM imaging, FTIR spectroscopy, dry and wet gas
permeation, evaluation of reusability, antifouling and mechanical properties,
photostability, surface hydrophilicity and pure water permeability (PWP) of the
produced membranes. According to the results, irrespective of solvent type,
ABS/PU membranes with higher PU content have lower porosity and smaller pore size
both of which contribute to enhanced dye rejection efficiency. This is while the
impact of PU content on the photostability of ABS/PU membranes was found to be
negligible. Additionally, the produced ABS/PU membranes exhibit good reusability
and antifouling properties. However, the mechanical properties of ABS/PU
membranes with higher PU contents are inferior to those with lower PU contents.
This contrast highlights the prominence of optimum PU content to make a trade-off
between dye rejection efficiency and mechanical properties. In this regard,
ABS/PU (60/40 w/w) membrane is recognized as the one with optimum composition.
Furthermore, it was found that regardless of PU content, membranes cast from DMF
based solutions exhibit superior rejection performance over those cast from NMP
based solutions. Overall, one can witness that employing ABS/PU membranes
provides a meritorious and clean approach to refine disperse and vat dye
wastewaters, a great threat to the environment and human health.
PMID- 28412619
TI - Denitrification potential in the subsurface environment in the Manawatu River
catchment, New Zealand: Indications from oxidation-reduction conditions,
hydrogeological factors, and implications for nutrient management.
AB - A sound understanding of the effects of hydrogeological factors on loss,
transport and transformation of farm nutrients is essential for predicting their
impacts on ecosystem health of receiving waters. We assessed the potential of
groundwater to attenuate nitrate through denitrification, and the distribution of
this potential across the Tararua Groundwater Management Zone (GWMZ) in the
Manawatu River catchment, New Zealand. We combined a number of methods in an
unprecedented manner to confirm findings and obtain supporting evidence for the
features that determine the subsurface denitrification characteristics. Our
results showed that the denitrification characteristics of groundwater varied
considerably in the Tararua GWMZ. The southern part of the Tararua GWMZ contained
mainly oxic groundwater with low potential to denitrify, whereas the middle and
northern parts of the Tararua GWMZ contained reduced groundwater with high
denitrification potential. The hydrogeological features that influence
denitrification potential in groundwater were identified as soil texture and
drainage class, and the aquifer material or rock type. Low dissolved oxygen
levels and nitrate concentrations were found in groundwater where the
combinations of soil and rock types had poor drainage characteristics as opposed
to higher concentrations in groundwater under well-drained soils and rocks (e.g.
gravels). Intensive pastoral farming over well-drained soils and rocks showed
high nitrate concentration in groundwater. This spatial variability in
denitrification potential of groundwater offers a targeted management of
nutrients runoff and leaching from pastoral lands to reduce their impacts on
receiving surface waters.
PMID- 28412620
TI - Adsorption of organic stormwater pollutants onto activated carbon from sewage
sludge.
AB - Adsorption filters have the potential to retain suspended pollutants physically,
as well as attracting and chemically attaching dissolved compounds onto the
adsorbent. This study investigated the adsorption of eight hydrophobic organic
compounds (HOCs) frequently detected in stormwater - including four polycyclic
aromatic hydrocarbons (PAHs), two phthalates and two alkylphenols - onto
activated carbon produced from domestic sewage sludge. Adsorption was studied
using batch tests. Kinetic studies indicated that bulk adsorption of HOCs
occurred within 10 min. Sludge-based activated carbon (SBAC) was as efficient as
tested commercial carbons for adsorbing HOCs; adsorption capacities ranged from
70 to 2800 MUg/g (Cinitial = 10-300 MUg/L; 15 mg SBAC in 150 mL solution; 24 h
contact time) for each HOC. In the batch tests, the adsorption capacity was
generally negatively correlated to the compounds' hydrophobicity (log Kow) and
positively associated with decreasing molecule size, suggesting that molecular
sieving limited adsorption. However, in repeated adsorption tests, where
competition between HOCs was more likely to occur, adsorbed pollutant loads
exhibited strong positive correlation with log Kow. Sewage sludge as a carbon
source for activated carbon has great potential as a sustainable alternative for
sludge waste management practices and production of a high-capacity adsorption
material.
PMID- 28412621
TI - Xanthium strumarium L. seed hull as a zero cost alternative for Rhodamine B dye
removal.
AB - Treatment of polluted water has been considered as one of the most important
aspects in environmental sciences. Present study explores the decolorization
potential of a low cost natural adsorbent Xanthium strumarium L. seed hull for
the adsorption of a toxic xanthene dye, Rhodamine B (RHB). The characterization
of the adsorbent revealed the presence of high amount of carbon, when exposed to
Electron Dispersive Spectroscopy (EDS). Further appreciable decolorization took
place which was confirmed by Fourier Transform Infrared Spectroscopy (FTIR)
analysis noticing shift in peaks. Isothermal studies indicated multilayer
adsorption following Freundlich isotherm. The rate of adsorption was supported by
second order kinetics directing a chemical phenomenon during the process with
dominance of film diffusion as the rate governing step. Moreover paper aims at
correlating the chemical arena to the mathematical aspect providing an in-depth
information of the studied treatment process. For proper assessment and
validation of the observed data, experimental data has been statistically treated
by applying different error functions namely, Chi-square test (chi2), Sum of
absolute errors (EABS) and Normalized standard deviation (NSD). Further practical
applicability of the low cost adsorbent was evaluated by continuous column mode
studies with 72.2% of dye recovery. Xanthium strumarium L. proved to be
environment friendly low cost natural adsorbent for decolorizing RHB from aquatic
system.
PMID- 28412622
TI - Population-production-pollution nexus based air pollution management model for
alleviating the atmospheric crisis in Beijing, China.
AB - In recent years, increscent emissions in the city of Beijing due to expanded
population, accelerated industrialization and inter-regional pollutant
transportation have led to hazardous atmospheric pollution issues. Although a
number of anthropogenic control measures have been put into use, frequent/severe
haze events have still challenged regional governments. In this study, a hybrid
population-production-pollution nexus model (PPP) is proposed for air pollution
management and air quality planning (AMP) with the aim to coordinate human
activities and environmental protection. A fuzzy-stochastic mixed quadratic
programming method (FSQ) is developed and introduced into a PPP for tackling
atmospheric pollution issues with uncertainties. Based on the contribution of an
index of population-production-pollution, a hybrid PPP-based AMP model that
considers employment structure, industrial layout pattern, production mode,
pollutant purification efficiency and a pollution mitigation scheme have been
applied in Beijing. Results of the adjustment of employment structure, pollution
mitigation scheme, and green gross domestic product under various environmental
regulation scenarios are obtained and analyzed. This study can facilitate the
identification of optimized policies for alleviating population-production
emission conflict in the study region, as well as ameliorating the hazardous air
pollution crisis at an urban level.
PMID- 28412623
TI - The urban heat island effect, its causes, and mitigation, with reference to the
thermal properties of asphalt concrete.
AB - The Urban Heat Island (UHI) is a phenomenon that affects many millions of people
worldwide. The higher temperatures experienced in urban areas compared to the
surrounding countryside has enormous consequences for the health and wellbeing of
people living in cities. The increased use of manmade materials and increased
anthropogenic heat production are the main causes of the UHI. This has led to the
understanding that increased urbanisation is the primary cause of the urban heat
island. The UHI effect also leads to increased energy needs that further
contribute to the heating of our urban landscape, and the associated
environmental and public health consequences. Pavements and roofs dominate the
urban surface exposed to solar irradiation. This review article outlines the
contribution that pavements make to the UHI effect and analyses localized and
citywide mitigation strategies against the UHI. Asphalt Concrete (AC) is one of
the most common pavement surfacing materials and is a significant contributor to
the UHI. Densely graded AC has low albedo and high volumetric heat capacity,
which results in surface temperatures reaching upwards of 60 degrees C on hot
summer days. Cooling the surface of a pavement by utilizing cool pavements has
been a consistent theme in recent literature. Cool pavements can be reflective or
evaporative. However, the urban geometry and local atmospheric conditions should
dictate whether or not these mitigation strategies should be used. Otherwise both
of these pavements can actually increase the UHI effect. Increasing the
prevalence of green spaces through the installation of street trees, city parks
and rooftop gardens has consistently demonstrated a reduction in the UHI effect.
Green spaces also increase the cooling effect derived from water and wind
sources. This literature review demonstrates that UHI mitigation techniques are
best used in combination with each other. As a result of the study, it was
concluded that the current mitigation measures need development to make them
relevant to various climates and throughout the year. There are also many
possible sources of future study, and alternative measures for mitigation have
been described, thereby providing scope for future research and development
following this review.
PMID- 28412624
TI - Effects of 1,25-dihydroxyvitamin D3 in an ovalbumin-induced allergic rhinitis
model.
AB - IL-17-producing Th17 cells play an important role in allergic airway diseases,
but their local expression and regulation in allergic rhinitis (AR) is not well
understood. This study investigated the effects of 1,25-dihydroxyvitamin D3 (1,25
(OH)2D3) on T-bet expression, Th1 cells, Th2 cells, Th17 cells and IL-33-positive
epithelial cells in AR. C57BL/6 mice were intranasally sensitized and challenged
with ovalbumin (OVA), and 1,25-(OH)2D3 was intraperitoneally injected into AR
mice. Cytokine levels were measured with enzyme-linked immunosorbent assays,
phenotypic analysis of Th1, Th2 and Th17 cells in the spleen was completed with
flow cytometry, and the CD4+IL-17+ cells in the Nasopharynx-associated lymphoid
tissue (NALT) and IL-33-positive cells in nasal mucosa was evaluated with
immunofluorescence microscopy. AR mice shown significantly increased Th2 and Th17
cell ratio in spleen, IL-17 level in serum, IL-5 and IL-13 levels in NALF but a
lower number of IL-33-positive epithelial cells and Th1 response (Th1 and
Tbet+Th1 cell ratio in the spleen and serum IFN-gamma level) than the control
mice.1,25-(OH)2D3 treatment significantly decreased the number of sneezing, nasal
rubbing, OVA-sIgE and IL-17 in serum, IL-5 and IL-13 levels in NALF, Th17 cell
ratio in the spleen and the histological of nasal mucosal but increased the
number of IL-33-positive epithelial cells in AR mice. However, 1,25-(OH)2D3
treatment did not significantly influence IFN-gamma level in serum, and Th1,
Tbet+Th1 and Th2 cell ratio in spleen. Thus, 1,25-(OH)2D3 may exert anti-allergic
effects by suppressing Th17 responses and local production of IL-5 and IL-13
cytokines.
PMID- 28412625
TI - Toxicity of two effluents from agricultural activity: Comparing the genotoxicity
of sugar cane and orange vinasse.
AB - Vinasse, produced by several countries as a by-product of agricultural activity,
has different alternatives for its reuse, mainly fertirrigation. Several
monocultures, such as sugar cane and orange crops, produce this effluent. Sugar
cane vinasse is already widely used in fertirrigation and orange vinasse has
potential for this intention. However, its use as a fertilizer has caused great
concern. Thus, ecotoxicological evaluation is extremely important in order to
assess the possible effects on the environment. Therefore, the aim of this study
was to evaluate the potential toxicity of vinasse of two different crops: sugar
cane and orange. For this purpose, bioassays with Allium cepa as a test organism
were performed with two vinasse dilutions (2.5% and 5%) to detect chromosomal
aberrations and micronucleus induction. The results showed that both types of
vinasse are able to induce chromosomal aberrations in meristematic cells, mainly
nuclear and anaphasic bridges, suggesting genotoxic potential. The induction of
micronuclei in cells of the F1 region suggests that the two residues have
mutagenic potential. Thus, caution is advised when applying these effluents in
the environment.
PMID- 28412626
TI - Quantification of heat shock protein 70 and acetylcholinesterase over a time
course suggests environmental adaptation in a foundational molluscan species.
AB - Waterways in urban areas often act as repositories for sewage, industrial waste,
and environmental contaminants. In response, inhabitants of these watersheds
undergo physiological adaptations specific to their respective environments.
Effects of these stressors can be assayed by quantification of various well
documented biomarkers in sentinel species such as the Atlantic Ribbed mussel,
Geukensia demissa, a native to the Bronx River Estuary, Bronx, NY, USA. Heat
shock protein 70 (Hsp70) is a universally expressed biomarker for an array of
environmental stressors including toxins and low dissolved oxygen. To better
understand the mechanisms by which organisms tolerate their contaminated
environments, we monitored the constitutive and heat shock-induced levels of two
proteins: Hsp70 and acetylcholinesterase (AChE) in natural populations of G.
demissa from differentially impacted sites: the Bronx River and Greenwich Cove
estuaries. We show that G. demissa from the Bronx River exhibits a higher level
of constitutive Hsp70, and launches a more rapid and robust heat shock response
than does its Greenwich Cove counterpart. In addition, AChE levels are recovered
more quickly in Bronx River mussels. Based on response pattern investigations
from heat stress as well as constitutive expression, we suggest that the
Hsp70/AChE chaperone/client relationship exemplifies the unique adaptive
mechanisms utilized by organisms in order to tolerate environmentally impacted
habitats. Results from this study offer important insights from an ecological
perspective into the molecular and cellular basis of stress response and provide
valuable information regarding adaptation to the increased demands of challenging
environments.
PMID- 28412627
TI - Exploratory factor analysis of fluoride removal efficiency associated with the
chemical properties of geomaterials.
AB - This study explored the chemical properties of geomaterials in relation with
their fluoride removal efficiencies from water under acidic conditions. Two types
each of as-received and engineered steel slags were tested, and their F- removal
efficiencies were compared with those of other common or commercially available
acid spill response materials. The chemical properties of the geomaterials were
analyzed by x-ray photoelectron spectroscopy to determine their surface elemental
compositions and by Brunauer-Emmett-Teller analysis to determine their surface
areas. The F- removal efficiencies were calculated based on the fluoride
concentrations in the remaining solutions using an ion chromatography technique.
A principal component analysis (PCA) was conducted to identify the dominant
independent variables that influenced the F- removal efficiencies, revealing that
the surface area was most closely correlated with the F- removal efficiency. A
microscopic analysis of the geomaterials, conducted using an energy dispersion
spectrometer technique after the F- sorption reaction had occurred revealed that
the local Al, Si, or O concentration was an important latent independent variable
for the F- removal efficiency. These variables had been hidden in the PCA
results. Therefore, aluminosilicate-rich geomaterials with a high surface area
offer primary candidates as effective sorbents for fluoride in water under acidic
conditions.
PMID- 28412628
TI - 4-nitroso-sulfamethoxazole generation in soil under denitrifying conditions:
Field observations versus laboratory results.
AB - The formation of 4-nitroso-sulfamethoxazole and 4-nitro-SMX, two transformation
products (TPs) of sulfamethoxazole (SMX) was investigated under batch soil slurry
experiments and in a field study. Due to their low occurrence levels (ng/L) in
environmental waters, a suitable analytical method based on liquid chromatography
- high resolution - mass spectrometry was developed. Consequently, field
observations revealed, for the first time, the occurrence of 4-nitroso-SMX in
groundwater at concentrations as high as 18ng/L.Nitric oxide (NO) steady-state
concentrations were determined in soil slurry experiments because this reactive
specie accounted for the formation of 4-nitroso-SMX and 4-nitro-SMX. Measurements
revealed that environmental SMX concentrations (0.2-2MUg/L) at neutral pH induced
the accumulation of nitric oxide. Under acidic conditions (pH<6), nitrous acid
(HONO) was the major source of nitric oxide while under neutral/basic conditions
nitric oxide release was related to the inhibition of denitrification processes.
Under laboratory experiments, SMX nitration reaction appeared to be an
irreversible transformation pathway, while 4-nitroso-SMX was slowly transformed
over time. The occurrence of 4-nitroso-SMX conditions was therefore unexpected in
the field study but could be due to its continuous input from soil and/or its
relative persistence under anoxic conditions. A mechanism for 4-nitroso-SMX
formation was proposed involving a nitrosative desamination pathway through a
phenyl radical.
PMID- 28412629
TI - Toxicological interactions of ibuprofen and triclosan on biological activity of
activated sludge.
AB - The growing use of pharmaceutical and personal care products increases their
concentrations in the wastewater entering treatment plants and their levels into
biological reactors. The most extended biological wastewater treatment is the
activated sludge process. The toxicity of ibuprofen and triclosan, individually
and combined, was studied by tracking the biological activity of the activated
sludge measuring oxygen uptake rate and the inhibition of the esterase activity.
Short-term exposure produced significant inhibition in oxygen uptake, with lower
damage to enzymatic activity. Median effect values for oxygen uptake inhibition
were 64+/-13mgL-1 and 0.32+/-0.07mgL-1 for ibuprofen and triclosan respectively
using 125mgL-1 activated sludge. For the inhibition of enzymatic activity values
were 633+/-63mgL-1 for ibuprofen and 1.94+/-0.32mgL-1 for triclosan. Results
indicated that oxygen uptake, related to primary activity of microorganisms, was
more strongly affected than the enzymatic activity associated to energy
consumption. Toxicity interactions were determined using the Combination Index
isobologram method. Results showed antagonism at lower values of affected
population, after which the mixtures tended to additivity and synergism. For the
case of enzymatic activity, the antagonism was less marked and the additivity
range was higher.
PMID- 28412630
TI - Phenol remediation by peroxidase from an invasive mesquite: Turning an
environmental wound into wisdom.
AB - The present study examines mesquite (Prosopis juliflora), an invasive species, to
yield peroxidase that may reduce hazards of phenolics to living organisms. As low
as 0.3U of low-purity mesquite peroxidase (MPx) efficiently remove phenol and
chlorophenols (90-92%) compared with Horseradish peroxidase (HRP) (40-60%). MPx
shows a very high removal efficiency (40-50%) at a wide range of pH (2-9) and
temperature (20-80 degrees C), as opposed to HRP (15-20%). At a high-level of the
substrate (2.4mM) and without the addition of PEG, MPx maintains a significant
phenolic removal (60->=92%) and residual activity (~25%). It proves the
superiority of MPx over HRP, which showed insignificant removal (10-12%) under
similar conditions, and no residual activity even with PEG addition. The root
elongation and plant growth bioassays confirm phenolic detoxification by MPx.
Readily availability of mesquite across the countries and easy preparation of MPx
from leaves make this tree as a sustainable source for a low-technological
solution for phenol remediation. This study is the first step towards converting
a biological wound of invasive species into wisdom and strength for protecting
the environment from phenol pollution.
PMID- 28412631
TI - Effectiveness of Physiotherapy interventions plus Extrinsic Feedback for neck
disorders: A systematic review with meta-analysis.
AB - PURPOSE: To systematically review the effectiveness of Physiotherapy
interventions combined with extrinsic feedback (EF) compared to Physiotherapy
interventions alone or control for the management of neck pain and disability.
METHODS: Randomized clinical trials were searched and retrieved from six
databases, from inception through August 2016. Risk of bias of included studies
was assessed using the PEDro scale. When possible data were pooled and Meta
analyses were conducted. The quality and strength of evidence for each outcome
was assessed using the GRADE approach. RESULTS: Eight studies (n = 677) were
included in the review. The pooled estimates suggested Physiotherapy intervention
+ EF was not superior to Physiotherapy intervention alone for disability (MD =
0.38; 95%CI = -0.91 to 0.18; I2 = 82%), but was superior for pain (MD = -0.37;
95%CI = -0.73 to -0.01; I2 = 68%). Physiotherapy intervention + EF was not
superior than control for disability scores (SMD = -3.94; 95%CI = -12.06 to 4.18;
I2 = 92%). Physiotherapy intervention + EF intervention was more effective than
control for pain scores at short-term (SMD = -1.44; 95%CI = -2.25 to-0.63; I2 =
50%). Most studies did not specify nor use the ideal characteristics of EF.
CONCLUSION: There is very low quality of evidence that Physiotherapy intervention
+ EF is more effective than Physiotherapy intervention alone or control for short
term pain, but not for disability. Physiotherapy intervention plus EF was more
effective than Physiotherapy alone for acute neck pain, but not for chronic pain
or disability. There was high risk of bias within included studies. Future
studies are likely to change the estimates of the effects of Physiotherapy
intervention plus EF on neck rehabilitation.
PMID- 28412632
TI - Seed dormancy and germination of the medicinal holoparasitic plant Cistanche
deserticola from the cold desert of northwest China.
AB - Cistanche deserticola is a holoparasitic plant with high medicinal value that
reproduces only by seeds. However, the requirements for seed dormancy break and
germination of this species remain unclear. The freshly matured dust-like seeds
consist of a water-permeable seed coat and an undifferentiated oval-shaped embryo
embedded in endosperm. No fresh seeds germinated in water or a 10-5 M fluridone
solution at any incubation temperature within 60 days. Length of embryos in seeds
incubated in warm- and cold-started stratification sequences had increased 10.4
and 11.7% after 50 and 40 weeks, respectively. After 6 months, length of embryos
in seeds stratified at 5 degrees C had increased by 12%. Germination of fresh
seeds and of seeds stratified at 5 degrees C for 6 months and then incubated in
mixed fluridone/gibberellic acid 3 (GA3) solutions at 30/20 degrees C germinated
to only 2.6 and 11.7%, respectively. Embryos of fresh seeds and of cold
stratified seeds had increased 29.4 and 15.8% in length, respectively, at the
time of germination, but they never differentiated into organs. The highest
germination (54.4%) was for seeds incubated in a 10-5 M solution of fluridone in
darkness in spring that had overwinter on the soil surface in the natural
habitat. Our study indicates that breaking of physiological dormancy (PD) occurs
first and then the embryo grows to a critical length (0.44 mm) without
differentiation into organs prior to seed germination. Seeds for which PD had
been broken were induced to germinate by fluridone and GA3 at high temperature.
Taken together, these results suggest that C. deserticola seeds have a
specialized kind of morphophysiological dormancy. This study reveals possible
ways to release seed dormancy that will be useful in propagating this medicinal
species.
PMID- 28412633
TI - Relationship among color development, anthocyanin and pigment-related gene
expression in 'Crimson Seedless' grapes treated with abscisic acid and sucrose.
AB - 'Crimson Seedless' is one of the most important table grape varieties in Chile,
but under certain environmental conditions, the fruit exhibits inadequate red
color development, causing economic losses due to lower product quality. The use
of plant growth regulators, such as abscisic acid (ABA) and ethylene, during
development increases the anthocyanin content of the skin, improving the color of
the berry. Recently, sucrose has been identified as a signaling molecule capable
of regulating the expression of genes of the anthocyanin biosynthesis pathway.
The aim of this study was to analyze the effect of application of ABA and/or
sucrose on color development and their relationship with anthocyanin metabolism.
Applications of ABA (400 ppm or 200 ppm) and/or sucrose (90 mM) were performed
close to the veraison stage. During development and at harvest, quality
attributes such as berry firmness, total soluble solids and titratable acidity
were not affected by these treatments. Increased red color development was
observed in fruits treated with ABA and/or sucrose, due to accumulation of
anthocyanins. Fruits subjected to sucrose treatment showed higher levels of
anthocyanins than untreated fruits but lower levels than fruits treated with ABA.
Increased expression of genes involved in anthocyanin biosynthesis was observed
in ABA- and sucrose-treated fruits compared to untreated fruits. Based on these
findings, we demonstrated that sucrose improved fruit color development by
increasing synthesis and accumulation of anthocyanins, thus allowing earlier
harvests and improving table grape quality.
PMID- 28412634
TI - Chitosan-induced immunity in Camellia sinensis (L.) O. Kuntze against blister
blight disease is mediated by nitric-oxide.
AB - Blister blight disease, caused by an obligate biotrophic fungal pathogen,
Exobasidium vexans Massee is posing a serious threat for tea cultivation in Asia.
As the use of chemical pesticides on tea leaves substantially increases the toxic
risks of tea consumption, serious attempts are being made to control such
pathogens by boosting the intrinsic natural defense responses against invading
pathogens in tea plants. In this study, the nature and durability of resistance
offered by chitosan and the possible mechanism of chitosan-induced defense
induction in Camellia sinensis (L.) O. Kuntze plants against blister blight
disease were investigated. Foliar application of 0.01% chitosan solution at 15
days interval not only reduced the blister blight incidence for two seasons, but
also maintained the induced expressions of different defense related enzymes and
total phenol content compared to the control. Defense responses induced by
chitosan were found to be down regulated under nitric oxide (NO) deficient
conditions in vivo, indicating that the observed chitosan-induced resistance is
probably activated via NO signaling. Such role of NO in host defense response was
further established by application of the NO donor, sodium nitroprusside (SNP),
which produced similar defense responses accomplished through chitosan treatment.
Taken together, our results suggest that increased production of NO in chitosan
treated tea plants may play a critical role in triggering the innate defense
responses effective against plant pathogens, including that causing the blister
blight disease.
PMID- 28412635
TI - Particle manipulations in non-Newtonian microfluidics: A review.
AB - Microfluidic devices have been widely used since 1990s for diverse manipulations
of particles (a general term of beads, cells, vesicles, drops, etc.) in a variety
of applications. Compared to the active manipulation via an externally imposed
force field, the passive manipulation of particles exploits the flow-induced
intrinsic lift and/or drag to control particle motion with several advantages.
Along this direction, inertial microfluidics has received tremendous interest in
the past decade due to its capability to handle a large volume of samples at a
high throughput. This inertial lift-based approach in Newtonian fluids, however,
becomes ineffective and even fails for small particles and/or at low flow rates.
Recent studies have demonstrated the potential of elastic lift in non-Newtonian
fluids for manipulating particles with a much smaller size and over a much wider
range of flow rates. The aim of this article is to provide an overview of the
various passive manipulations, including focusing, separation, washing and
stretching, of particles that have thus far been demonstrated in non-Newtonian
microfluidics.
PMID- 28412636
TI - Facile size-controlled preparation of highly photocatalytically active ZnCr2O4
and ZnCr2O4/Ag nanostructures for removal of organic contaminants.
AB - The ZnCr2O4 nanoparticles were synthesized and characterized by different
techniques such as; XRD, SEM, EDS, VSM, TEM and IR. In order to modify the
morphology of structures, various alkaline and capping agents were used. For this
work TETA, en and NH3 as alkaline agents and salicylaldehyde, N,N'
(bis(salicylidene)-ethylene-1,2-diamine) and SDS as capping agents were employed.
The cubic morphology for the ZnCr2O4 nanoparticles were obtained by using TETA
and N,N'-(bis(salicylidene)-ethylene-1,2-diamine). When SDS and TETA were used,
very uniform spherical zinc chromite nanoparticles with fine grain size were
produced. Then on the surface of these nanoparticles, Ag nanoparticles were
covered by photodeposition method. For investigation photocatalytic activity of
the nanoparticles, several factors such as various azo dyes, temperature, grain
size and morphology were investigated. Also by using of ZnCr2O4/Ag nanoparticles
prepared polymer based nanocomposite. Results indicate that, nanoparticles can
enhance the thermal stability of the PVA matrix.
PMID- 28412637
TI - Photoimmobilization of zwitterionic polymers on surfaces to reduce cell adhesion.
AB - Simple and robust methods for modifying hydrophobic polymer surfaces with
zwitterionic polymers using UV irradiation were developed. Two random
zwitterionic copolymers consisting of either carboxybetaine or sulfobetaine
methacrylamide monomers and monomers bearing a photolabile azidophenyl group were
directly photoimmobilized on polymeric surfaces (polyester, polyethylene and
polystyrene) via covalent interactions in a spatially controlled manner. These
copolymers were also electrospun to form self-standing mats. The modified
surfaces were characterized by X-ray photoelectron spectroscopy, atomic force
microscopy, infrared spectroscopy and contact angle measurements. The
electrospinning method involved the use of a trifluoroethanol solution with a
copolymer concentration in the range from 2 to 10wt.%. BHK 21 cell adhesion to
both modified surfaces and mats was dramatically reduced compared to unmodified
surfaces.
PMID- 28412638
TI - Influence of ionic liquid on pseudocapacitance performance of electrochemically
synthesized conductive polymer: Electrochemical and theoretical investigation.
AB - This study demonstrates a method for improving supercapacitive performance of
electrochemically synthesized conductive polymer. In this regards, 1-Butyl-3
methyl imidazolium hexafluorophosphate (BI) as a new high efficient ionic liquid
was synthesized using chemical approach and then fabricated POAP/BI films by
electro-polymerization of POAP in the presence of BI to serve as the active
electrode for electrochemical supercapacitor. Theoretical study (AIM) and
electrochemical analysis have been used for characterization of ionic liquid and
POAP/BI composite film. Different electrochemical methods including galvanostatic
charge-discharge experiments, cyclic voltammetry and electrochemical impedance
spectroscopy are carried out in order to investigate the performance of the
system. This work introduces new most efficient materials for electrochemical
redox capacitors with advantages including ease synthesis, high active surface
area and stability in an aqueous electrolyte.
PMID- 28412639
TI - Aggregation of thermoresponsive core-shell nanoparticles: Influence of particle
concentration, dispersant molecular weight and grafting.
AB - Thermoresponsive core-shell nanoparticles represent an interesting class of
materials with a triggered solubility transition. However, depending on the
system, their aggregation behavior above the lower critical solution temperature
(LCST) is ambiguous and obviously linked to a multitude of parameters. The
induced aggregation of a set of well characterized poly(N-isopropylacrylamide)
nitrodopamine grafted superparamagnetic iron oxide nanoparticles is investigated
with respect to the PNIPAM molecular weight (5-30kDa) and concentration using
differential scanning calorimetry and temperature-cycled dynamic light scattering
measurements. PNIPAM molecular weight clearly influences the thermoresponsiveness
of the material, including LCST, colloidal aggregation and deaggregation as well
as transition enthalpy. Furthermore, a strong impact of topology (grafted vs.
free polymer chain) on the thermoresponsiveness is observed. Cluster size above
the LCST depends on concentration and PNIPAM molecular weight. This makes it
reasonable to conduct aggregation experiments under constant (high) particle
molar concentration for comparative studies. Similarly, low particle molar
concentration is used to elucidate individual particle shell properties by
avoiding masking inter-particle effects.
PMID- 28412640
TI - Is a hilly neighborhood environment associated with diabetes mellitus among older
people? Results from the JAGES 2010 study.
AB - BACKGROUND: Although living in a hilly environment may promote muscular activity
in the daily lives of residents, and such activity may prevent diabetes mellitus,
few studies have focused on the impact of living in a hilly environment on
diabetes mellitus. The purpose of this study was to investigate the impact of a
hilly neighborhood environment on DM in older people. METHODS: We used data from
the Japan Gerontological Evaluation Study, a population-based, cross-sectional
study of individuals aged 65 or older without long-term care needs in Japan,
which was conducted in 2010. A total of 8904 participants in 46 neighborhoods had
responded to the questionnaire and undergone a health check. Diabetes mellitus
was diagnosed as HbA1c >= 6.5% and those undergoing treatment for diabetes
mellitus. Poorly controlled diabetes mellitus was diagnosed in those without
other chronic diseases who had an HbA1c > 7.5%, and in those with other chronic
diseases if their HbA1c was >8.0%. Neighborhood environment was evaluated based
on the percentage of positive responses in the questionnaire and geographical
information system data. A multilevel analysis was performed, adjusted for
individual-level risk factors. Furthermore, sensitivity analysis was conducted
for those who were undergoing treatment for diabetes mellitus (n = 1007).
RESULTS: After adjustment for other physical environmental and individual
covariates, a 1 interquartile range increase (1.48 degrees ) in slope in the
neighborhood decreased the risk of poorly controlled diabetes mellitus by 18%
(odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.70-0.97). Sensitivity
analysis confirmed that larger slopes in the neighborhood showed a significant
protective effect against diabetes mellitus among those who were undergoing
treatment for diabetes mellitus (OR: 0.73, 95% CI: 0.59-0.90). CONCLUSION: A
hilly neighborhood environment was not associated with diabetes mellitus, but was
protective against poorly controlled diabetes mellitus.
PMID- 28412641
TI - The gap between entitlement and access to healthcare: An analysis of "candidacy"
in the help-seeking trajectories of asylum seekers in Montreal.
AB - In 2012 the Canadian government made significant cuts to its historically strong
federal refugee health coverage plan. While this policy had negligible effects on
the level of coverage provided to asylum seekers in Quebec, there is evidence
that this group nonetheless experienced reduced healthcare access during the
period of polarized national debate that ensued. This study engaged the
"candidacy" model of healthcare access to illuminate factors contributing to the
observed gap between entitlement and access. Twenty-five semi-structured
interviews were conducted with asylum seekers in Montreal to elicit narrative
accounts of difficulties encountered in the pursuit of healthcare. Thematic
content analysis in conjunction with a holistic examination of help-seeking
trajectories revealed several important barriers to obtaining care, including
widespread confusion and misinformation about refugee health coverage, cumbersome
administrative procedures specific to asylum seekers, and long wait times.
Feelings of marginalization and insecurity associated with precarious migratory
status appeared to amplify the effects of these barriers to care such that even a
minor access difficulty could have dramatic effects on future help-seeking and
access outcomes. Demonstrating awareness of public discourses interrogating their
deservingness of health coverage, participants often interpreted access
difficulties as evidence of health professionals' unwillingness to serve them.
Such interpretations conspired with fears associated with the asylum claim
process to suppress self-advocacy, further help-seeking, and at times even
information-seeking. This finding is particularly significant in that it suggests
a mechanism through which hostile public representations of forced migrants
increasingly prevalent in Western host countries-can themselves endanger the
physical, psychological, and social health of highly disadvantaged populations,
even in the presence of strong entitlement policies. We close with reflections on
how theoretical models of healthcare access might be adjusted to better
accommodate the unique experiences of precarious status migrants.
PMID- 28412642
TI - Impact of duration of hypotension prior to norepinephrine initiation in medical
intensive care unit patients with septic shock: A prospective observational
study.
AB - PURPOSE: To determine the impact of duration of hypotension prior to
norepinephrine initiation on outcomes in MICU patients with septic shock. We
hypothesized increased duration of hypotension prior to norepinephrine initiation
would be associated with an increased risk for ICU mortality. MATERIALS AND
METHODS: We conducted a prospective-observational study in the MICU of a single
center tertiary academic medical center. We enrolled 160 adults >=18years old
with septic shock. Descriptive statistics were computed for demographic and
outcome variables. Primary logistic regression analysis was adjusted for severity
of illness. RESULTS: The mean age of our patients was 59years (+/-17); 42% were
female; the mean APACHE II score was 24.1 (+/-8.0), and the mean SOFA score was
9.6 (+/-4.0). Median duration of hypotension prior to norepinephrine initiation
was 3.6h (IQR 1.6-9.9). Duration of hypotension prior to norepinephrine did not
increase the risk for ICU mortality (OR 1.03 per hour after hypotension, 95% CI:
0.98-1.09, p=0.20). CONCLUSION: Duration of hypotension less than one hour and
greater than one hour prior to norepinephrine initiation in MICU patients with
septic shock is not associated with an increased risk for ICU mortality.
PMID- 28412643
TI - My action lasts longer: Potential link between subjective time and agency during
voluntary action.
AB - Time perception distorts across different phases of bodily movement. During motor
execution, sensory feedback matching an internal sensorimotor prediction is
perceived to last longer. The sensorimotor prediction also underlies sense of
agency. We investigated association between subjective time and agency during
voluntary action. Participants performed hand action while watching a video
feedback of their hand with various delays to manipulate agency. The perceived
duration and agency over the video feedback were judged. Minimal delay of the
video feedback resulted in longer perceived duration than the actual duration and
stronger agency, while substantial feedback delay resulted in shorter perceived
duration and weaker agency. These fluctuations of perceived duration and agency
were nullified by the feedback of other's hand instead of their own, but not by
inverted feedback from a third-person perspective. Subjective time during action
might be associated with agency stemming from sensorimotor prediction, and self
other distinction based on bodily appearance.
PMID- 28412644
TI - An association of health behaviors with depression and metabolic risks: Data from
2007 to 2014 U.S. National Health and Nutrition Examination Survey.
AB - BACKGROUND: Both depression and metabolic syndrome (MetS) confer an increased
risk of developing type 2 diabetes (T2D) and cardiovascular disease. Accumulating
evidence suggests healthy behaviors are crucial to maintain, improve and manage
chronical disease and mental health; and unhealthy diet and sedentary behavior
were found two major risk factors of MetS. The objective of this study was to
investigate whether health behaviors (alcohol consumption, smoking, diet and
recreational physical activity) are associated with depression and metabolic
syndrome simultaneously. METHODS: This study included 1300 participants aged 20
years and over who had answered mental health-depression screener questions (PHQ
9) and finished examinations and laboratory tests related to five risk factors of
MetS during the U.S. National Health and Nutrition Examination Survey (NHANES)
2007-2014. A set of series of weighted logistic regression models were used to
investigate the aforementioned relationship. RESULTS: The prevalence of
depression among U.S. adults is 15.08%. The two most often reported depression
symptoms were "Trouble sleeping or sleeping too much" and "Feeling tired or
having little energy", with rates of14.68% and 13.09%, respectively. Participants
who engaged in only light physical activity were more likely to have been
identified as experiencing depression and MetS than those who engaged in vigorous
physical activity with odd ratios 3.18 (95% CI: 1.59, 6.37) and 3.50 (95%CI:
2.17, 5.63), respectively. Individuals in the study having poor diets were more
likely to suffer from depression than those eating good diets (OR=2.17, 95%CI:
1.47, 3.22). CONCLUSION: Physical activity is strongly and inversely associated
with depression and MetS. Diet is significantly associated with depression rather
than MetS in this study.
PMID- 28412645
TI - A hidden structural vulnerability in the thrombospondin-2 deficient aorta
increases the propensity to intramural delamination.
AB - Mice lacking thrombospondin-2 (TSP2) represent an animal model of impaired
collagen fibrillogenesis. Collagen constitutes ~1/3 of the wall of the normal
murine descending thoracic aorta (DTA) and is thought to confer mechanical
strength at high pressures. Microstructural analysis of the DTA from TSP2-null
mice revealed irregular and disorganized collagen fibrils in the adventitia and
at the interface between the media and adventitia. Yet, biaxial mechanical tests
performed under physiologic loading conditions showed that most mechanical
metrics, including stress and stiffness, were not different between mutant and
control DTAs at 20- and 40-weeks of age, thus suggesting that the absence of TSP2
is well compensated under normal conditions. A detailed bilayered analysis of the
wall mechanics predicted, however, that the adventitia of TSP2-null DTAs fails to
engage at high pressures, which could render the media vulnerable to mechanical
damage. Failure tests confirmed that the pressure at which the DTA ruptures is
significantly lower in 20-week-old TSP2-null mice compared to age-matched
controls (640+/-37 vs. 1120+/-45mmHg). Moreover, half of the 20-week-old and all
40-week-old mutant DTAs failed by delamination, not rupture. This delamination
occurred at the interface between the media and the adventitia, with separation
planes often observed at ~45 degrees with respect to the circumferential/axial
directions. Combined with the observed microstructural anomalies, our theoretical
experimental biomechanical results suggest that TSP2-null DTAs are more
susceptible to material failure when exposed to high pressures and this
vulnerability may result from a reduced resistance to shear loading at the
medial/adventitial border.
PMID- 28412646
TI - A longitudinal study of the mechanical properties of injured brain tissue in a
mouse model.
AB - Mechanical properties of brain tissue are crucial to understand the mechanism of
traumatic brain injury (TBI). Over the past several decades, most of the studies
focused on healthy brain tissues, while few of them are about the injured
tissues. Therefore, limited knowledge is known about the mechanical properties of
the injured brain tissues. In this study, we used an in vivo mouse model with a
weight drop device to study injured brain tissues. Around the injury site,
mechanical properties of the injured, neighboring, and the corresponding
contralateral regions of interest (ROIs) were measured over five temporal points
by indentation. Longitudinal and regional comparisons of the mechanical
properties revealed that the ROI of the injured tissue had a higher elastic
modulus than the contralateral counterpart one-hour post-injury. However, the
elastic modulus decreased one-day post-injury and recovered to be close to the
contralateral ROI in 7 days. The elastic modulus curves of the injured and the
contralateral counterpart ROIs crossed at time points of 12h and 1 day post
injury, where two significant increases of glial fibrillary acidic protein (GFAP)
positive cells were observed. Biological staining results indicated that both the
astrocytic responses and the morphological structure could affect the mechanical
properties of the injured tissue. The observed longitudinal changes of the
mechanical properties at the tissue level and the morphological and biological
changes at the cellular level provide insights into understanding the mechanism
of TBI. Results are also meaningful for applying emerging in vivo diagnostic
tools such as magnetic resonance elastography (MRE) in TBI detection.
PMID- 28412647
TI - Ecofriendly lignocellulose pretreatment to enhance the carboxylate production of
a rumen-derived microbial consortium.
AB - Innovative dry chemo- and chemo-mechanical pretreatments form an interesting
approach for modifying the native physico-chemical composition of lignocellulose
facilitating its microbial conversion to carboxylates. Here, the impact of four
dry-pretreatment conditions on the microbial transformation of wheat straw was
assessed: milling to 2mm and 100um, and NaOH chemical impregnation at high
substrate concentrations combined with milling at 2mm and 100um. Pretreatment
effect was assessed in the light of substrate structure and composition, its
impact on the acidogenic potential and the major enzyme activities of a rumen
derived microbial consortium RWS. Chemo-mechanical pretreatment strongly modified
the substrate macroporosity. The highest carboxylate production rate was reached
after dry chemo-mechanical treatment with NaOH at 100um. A positive impact of the
dry chemo-mechanical treatment on xylanase activity was observed also. These
results underline that increasing substrate macroporosity by dry chemo-mechanical
pretreatment had a positive impact on the microbial acidogenic potential.
PMID- 28412648
TI - Content decline of SERCA inhibitors saikosaponin a and d attenuates
cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri.
AB - Improper usage of unprocessed Radix bupleuri root (chaihu) may cause
cardiotoxicity and liver injury. Baking herb with vinegar is believed to
attenuate the adverse responses. However, the chemical and molecular basis
involved remained unclear. To this end, we investigated the in vitro toxicity of
saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and b2. Results
showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic
reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger
toxic responses on cardiomyocytes and hepatocytes than the other three
saikosaponins in equivalent concentrations. Further, SSa and SSd induced LC3
puncta formation in U2OS-mCherry-EGFP-LC3 cells. Blockage of autophagy by 3
methyladenine did not abrogate the cytotoxicities induced by SSa and SSd. In
parallel, none of SSc, SSb1, or SSb2 caused cell injury. Our study reveals how
changes in chemical ingredients are connected to the toxicity of Chaihu during
vinegar baking process and also provides a guidance for structure optimization to
reduce drug induced toxicity.
PMID- 28412649
TI - Proinflammatory effects of diesel exhaust particles from moderate blend
concentrations of 1st and 2nd generation biodiesel in BEAS-2B bronchial
epithelial cells-The FuelHealth project.
AB - Biodiesel fuel fuels are introduced at an increasing extent as a more carbon
neutral alternative to reduce CO2-emissions, compared to conventional diesel
fuel. In the present study we have investigated the impact of increasing the use
of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend
(B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd
generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic
Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro
system. Human bronchial epithelial BEAS-2B cells were exposed for 4 and 20h to
DEP from B7, B20 and SHB at different concentrations, and examined for effects on
gene expression of interleukin 6 (IL-6), CXCL8 (IL-8), CYP1A1 and heme oxygenase
1 (HO-1). The results show that both B20 and SHB were more potent inducers of IL
6 expression compared to B7. Only B20 induced statistically significant increases
in CXCL8 expression. By comparison the rank order of potency to induce CYP1A1 was
SHB>B7>B20. No statistically significant difference were observed form HO-1
expression, suggesting that the differences in cytokine responses were not due to
oxidative stress. The results show that even moderate increases in biodiesel
blends, from 7% to 20%, may increase the proinflammatory potential of emitted DEP
in BEAS-2B cells. This effect was observed for both addition of 1st generation
FAME and 2nd generation HVO biodiesel.
PMID- 28412650
TI - Comparative effects of cholesteryl ester transfer protein inhibition, statin or
ezetimibe on lipid factors: The ACCENTUATE trial.
AB - BACKGROUND AND AIMS: The optimal approaches to management of patients treated
with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study
aimed to compare the effects of adding the cholesteryl ester transfer protein
inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin
treated high-vascular risk patients on lipid parameters. METHODS: 366 patients
with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated
with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40
mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe
10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the
United States. Lipid parameters, safety and tolerability were measured. RESULTS:
Addition of evacetrapib significantly reduced LDL-C (-33%) compared with
ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%,
p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe
(p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29%
(p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%),
apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated
efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1
mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe,
p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of
evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe
(p=0.02). CONCLUSIONS: While evacetrapib improved traditional atherogenic and
putative protective lipid measures compared with ezetimibe and increasing statin
dose in patients with ASCVD and/or diabetes, it also adversely affected novel
atherogenic risk factors. These findings may contribute to the lack of clinical
benefit observed in the ACCELERATE trial.
PMID- 28412651
TI - Time-dependent effect of rutin on skin fibroblasts membrane disruption following
UV radiation.
AB - Chronic exposure of the skin to solar UV radiation induces a number of biological
alterations, including a redox imbalance; therefore, there is an urgent need for
skin cells protective compounds. The aim of this study was to determine the
effects of natural, previously extensively examined, polyphenol with antioxidant
properties - rutin, on UV-induced skin fibroblasts membrane disruption.
Accordingly, fibroblasts exposed to UVA and UVB irradiation were incubated with
rutin (12h before and/or up to 24h after irradiation), and the structural and
metabolic changes were examined. Rutin penetration through the fibroblast
phospholipid bilayer was aided by UVA-induced bilitranslocase activity 2-4h after
irradiation, while UVB irradiation led to enhanced phospholipid peroxidation and
higher membrane permeability to facilitate the interaction of rutin with
phospholipids. Lipidomic analysis revealed that 4h of rutin treatment also
partially prevented UVA/B-induced increase in phosphatidylethanolamine and
phosphatidylcholine level, as well as their membrane localization, which resulted
in an enhanced zeta potential in the cells and liposomes. Moreover, rutin 2h
following irradiation, in a various degree, prevented the increased in
phospholipase A2 activity and ROS generation, and partially protected against the
reduction of arachidonic and linoleic acids level and the lipid peroxidation
product 4-hydroxynonenal level increase. Rutin effectively prevented against
decrease in glutathione peroxidase, glutathione and vitamins E and C
activities/levels, particularly 2h following UVA irradiation. In conclusion,
highest skin fibroblasts membrane level of rutin occurred in 2-4h following UVA/B
radiation results in its strongest effect on biomembrane structure and functions
and cellular antioxidant system irrespective of the radiation type.
PMID- 28412652
TI - During yeast chronological aging resveratrol supplementation results in a short
lived phenotype Sir2-dependent.
AB - Resveratrol (RSV) is a naturally occurring polyphenolic compound endowed with
interesting biological properties/functions amongst which are its activity as an
antioxidant and as Sirtuin activating compound towards SIRT1 in mammals. Sirtuins
comprise a family of NAD+-dependent protein deacetylases that are involved in
many physiological and pathological processes including aging and age-related
diseases. These enzymes are conserved across species and SIRT1 is the closest
mammalian orthologue of Sir2 of Saccharomyces cerevisiae. In the field of aging
researches, it is well known that Sir2 is a positive regulator of replicative
lifespan and, in this context, the RSV effects have been already examined. Here,
we analyzed RSV effects during chronological aging, in which Sir2 acts as a
negative regulator of chronological lifespan (CLS). Chronological aging refers to
quiescent cells in stationary phase; these cells display a survival-based
metabolism characterized by an increase in oxidative stress. We found that RSV
supplementation at the onset of chronological aging, namely at the diauxic shift,
increases oxidative stress and significantly reduces CLS. CLS reduction is
dependent on Sir2 presence both in expired medium and in extreme Calorie
Restriction. In addition, all data point to an enhancement of Sir2 activity, in
particular Sir2-mediated deacetylation of the key gluconeogenic enzyme
phosphoenolpyruvate carboxykinase (Pck1). This leads to a reduction in the amount
of the acetylated active form of Pck1, whose enzymatic activity is essential for
gluconeogenesis and CLS extension.
PMID- 28412653
TI - The relationship between dioxins exposure and risk of prostate cancer with
steroid hormone and age in Vietnamese men.
AB - Although Vietnam's massive herbicide exposure in 1960s and 1970s was clearly
injurious to health, not all causal relationships have been clarified. We
therefore explored associations among dioxins, steroid hormones, age and prostate
cancer risk in men. We compared serum levels of dioxin, steroid hormones and
prostate specific antigen (PSA) in men aged 56-81years from herbicide-exposed
hotspots (n=50) with those from non-sprayed regions (n=48). Mean serum levels of
dioxin congeners in the hotspot group were 1.5-11.3 times higher than the non
sprayed group depending on specific compound. Levels of testosterone, estradiol
and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in the hotspot group
were also significantly higher than in non-sprayed group. Estradiol levels were
significantly related to levels of several specific dioxin derivatives in both
group. Significant positive correlations were also found between DHT and 1234678
HpCDD or 1234678-HpCDF; and between 3beta-HSD activity and 123678-HxCDD, 123478
HxCDF, 123678-HxCDF, or HxCB#169. After adjusting for age, body mass index, and
tobacco use, multiple linear regressions showed levels of dihydrotestosterone
(DHT), estradiol, testosterone and 3beta-HSD activity were not associated with
dioxins in the two groups; however, levels of DHT, testosterone and 3beta-HSD
activity increased significantly with age in the hotspot group. The hotspot and
non-sprayed groups did not significantly differ in PSA levels. But six of the
hotspot subjects had PSA levels >3ng/mL, 3 of whom were suspected to have
prostate cancer (PC) after digital rectal examination. Our findings suggest that
dioxin exposure can lead to increased levels of several sex steroid hormones with
age. The correlation of dioxin with steroid hormone levels and prostate cancer
risk should be studied further.
PMID- 28412654
TI - Nigella sativa, a traditional Tunisian herbal medicine, attenuates bleomycin
induced pulmonary fibrosis in a rat model.
AB - The present study investigated the effects of Nigella sativa oil (NSO) on
bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary
fibrosis (PF) was established by intratracheal instillation of BLM, and the
effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was
studied over a period of 50daysusing 1H RMN analysis on the urine and broncho
alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and
fibrosis) and immunohistochemical (TGF-beta1 density) changes were evaluated.
Results found that the BLM group showed a significant increase in inflammatory
index (II), fibrosis score (FS) and TGF-beta1 distribution in the lung
inflammatory infiltrate, accompanied by a decreased urinary secretion of Krebs
cycle intermediates, including acetate, pyruvate, carnitine, trimethylamine-N
oxide and succinate. However, at the same time point, NSO treated rats had a
reduced II and FS, and had an increased urinary secretion of histidine, fumarate,
allantoin and malate. In conclusion, NSO treatment attenuated the effects of BLM
induced PF, by supporting lung, liver and kidney activity in resisting PF. These
findings provide an insight into the preventive and therapeutic potential of NSO
in the treatment of PF.
PMID- 28412655
TI - Parkinson's disease and pesticides: A meta-analysis of disease connection and
genetic alterations.
AB - Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that
occurs due to interactions between genetic and environmental factors.
Observational studies have shown a link between exposure to pesticides and the
risk of PD. We performed this study to systemically review published case-control
studies and estimate quantitatively the association between pesticide exposure
and PD. We searched Medline (through PubMed) for eligible case-control studies.
The association between pesticide exposure and PD risk or occurrence of certain
genetic alterations, related to the pathogenesis of PD was presented as odds
ratios (OR) and pooled under the random effects model, using the statistical add
in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is
linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant
heterogeneity among included studies. Exposure to pesticides increased the risk
of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97,
95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI
[1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no
statistically significant association between exposure to pesticides and
alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI
[0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91,
2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta
analysis provides evidence that pesticide exposure is significantly associated
with the risk of PD and alterations in genes involved in PD pathogenesis.
However, the underlying mechanism of this association and the effect of the
duration of exposure or the type of pesticides should be addressed by future
research.
PMID- 28412656
TI - Design optimization of embedded ultrasonic transducers for concrete structures
assessment.
AB - In the last decades, the field of structural health monitoring and damage
detection has been intensively explored. Active vibration techniques allow to
excite structures at high frequency vibrations which are sensitive to small
damage. Piezoelectric PZT transducers are perfect candidates for such testing due
to their small size, low cost and large bandwidth. Current ultrasonic systems are
based on external piezoelectric transducers which need to be placed on two faces
of the concrete specimen. The limited accessibility of in-service structures
makes such an arrangement often impractical. An alternative is to embed
permanently low-cost transducers inside the structure. Such types of transducers
have been applied successfully for the in-situ estimation of the P-wave velocity
in fresh concrete, and for crack monitoring. Up to now, the design of such
transducers was essentially based on trial and error, or in a few cases, on the
limitation of the acoustic impedance mismatch between the PZT and concrete. In
the present study, we explore the working principles of embedded piezoelectric
transducers which are found to be significantly different from external
transducers. One of the major challenges concerning embedded transducers is to
produce very low cost transducers. We show that a practical way to achieve this
imperative is to consider the radial mode of actuation of bulk PZT elements. This
is done by developing a simple finite element model of a piezoelectric transducer
embedded in an infinite medium. The model is coupled with a multi-objective
genetic algorithm which is used to design specific ultrasonic embedded
transducers both for hard and fresh concrete monitoring. The results show the
efficiency of the approach and a few designs are proposed which are optimal for
hard concrete, fresh concrete, or both, in a given frequency band of interest.
PMID- 28412657
TI - Potential-resolved "in-electrode" type electrochemiluminescence immunoassay based
on functionalized g-C3N4 nanosheet and Ru-NH2 for simultaneous determination of
dual targets.
AB - Here, a novel potential-resolved "in-electrode" type electrochemiluminescence
(ECL) immunosensor was fabricated based on two different types of luminant Ru-NH2
and AuNPs/g-C3N4 to realize simultaneous detection of dual targets. In this
strategy, anti-CA1251 and anti-SCCA1 were immobilized on bare gold electrode as
capture probes, which could catch the two corresponding target CA125 and SCCA,
and the immobilization of the signal tags was allowed via the interaction between
antigen and antibody. In this process, (Ru&anti-CA1252)@GO and anti-SCCA2-AuNPs/g
C3N4 could exhibit two strong and stable ECL emissions at 1.25V and -1.3V
respectively, which could be used as effective signal tags. Taking advantage of
"in-electrode" type ECL immunosensor, all the electrochemiluminophores near the
outer Helmholtz plane are "effective" in participating in the electrochemical
reactions and emitting ECL signals. Therefore, the dual targets CA125 and SCCA
could be detected within the linear ranges of 0.001-100U/mL and 0.001-100ng/mL,
with detection limits of 0.4mU/mL and 0.33pg/mL, respectively. All these results
demonstrated that the present potential-resolved "in-electrode" type
electrochemiluminescence approach provided a promising analytical method for dual
targets analysis with the advantages of simple analytical procedure, small sample
volume and lower cost, which made the proposed method potential for clinical
detection.
PMID- 28412658
TI - CdS:Mn quantum dot-functionalized g-C3N4 nanohybrids as signal-generation tags
for photoelectrochemical immunoassay of prostate specific antigen coupling
DNAzyme concatamer with enzymatic biocatalytic precipitation.
AB - A new photoelectrochemical (PEC) immunosensor based on Mn-doped CdS quantum dots
(CdS:Mn QDs) on g-C3N4 nanosheets was developed for the sensitive detection of
prostate specific antibody (PSA) in biological fluids. The signal derived from
the as-synthesized Cd:Mn QDs-functionalized g-C3N4 nanohybrids via a hydrothermal
method and was amplified through DNAzyme concatamers on gold nanoparticles
accompanying enzymatic biocatalytic precipitation. Experimental results by UV-vis
absorption spectra and photoluminescence revealed that CdS:Mn QDs/g-C3N4
nanohybrids exhibited higher photocurrent than those of CdS:Mn QDs and g-C3N4
alone. Upon addition of target PSA, a sandwich-type immunoreaction was carried
out between capture antibodies and the labeled detection antibodies. Accompanying
introduction of gold nanoparticles, the labeled initiator strands on the AuNPs
triggered hybridization chain reaction and the formation of DNAzyme concatamers
in the presence of hemin. The formed DNAzyme catalyzed 4-chloro-1-naphthol (4-CN)
to produce an insoluble/insulating precipitate on the Mn:CdS QDs/g-C3N4, and
blocked the light harvesting of Mn:CdS QDs/g-C3N4, thus resulting in the
decreasing photocurrent. Under optimal conditions, the immunosensor exhibited
good photocurrent responses for determination of target PSA, and allowed
detection of PSA at a concentration as low as 3.8pgmL-1. The specificity,
reproducibility and precision of this system were acceptable. Significantly, this
methodology was further evaluated for analyzing human serum samples, giving well
matched results with referenced PSA enzyme-linked immunosorbent assay (ELISA)
method.
PMID- 28412659
TI - Development of near-infrared ratiometric fluorescent probe based on cationic
conjugated polymer and CdTe/CdS QDs for label-free determination of glucose in
human body fluids.
AB - Quantum dots (QDs) have attracted extensive attention in biomedical applications,
because of their broad excitation spectra, narrow and symmetric emission peaks
etc. Furthermore, near-infrared (NIR) QDs have further advantages including low
autofluorescence, good tissue penetration and low phototoxicity. In this work,
the electrostatic interaction and fluorescence resonance energy transfer (FRET)
between NIR CdTe/CdS QDs and cationic conjugated polymer (CCP) was studied for
the first time. Based on the newly discovered phenomena and the result that
hydrogen peroxide (H2O2) can efficiently quench the fluorescence of NIR CdTe/CdS
QDs, a novel NIR ratiometric fluorescent probe for determination of H2O2 and
glucose was developed. Under the optimized conditions, the detection limit of
H2O2 and glucose assay were 0.1mM and 0.05mM (S/N=3), with a linear range of 0.2
4mM and 0.1-5mM, respectively. Because of the NIR spectrum, this ratiometric
probe can be also applied for the determination of glucose in whole blood samples
directly, providing a valuable platform for glucose sensing in clinic diagnostic
and drug screening.
PMID- 28412660
TI - Gold nanoparticle-based low limit of detection Love wave biosensor for
carcinoembryonic antigens.
AB - In this work, a Love wave biosensing platform is described for detecting cancer
related biomarker carcinoembryonic antigen (CEA). An ST 90 degrees -X quartz Love
wave device with a layer of SiO2 waveguide was combined with gold nanoparticles
(Au NPs) to amplify the mass loading effect of the acoustic wave sensor to
achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au
NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich
immunoassay. The unamplified detection limit of the Love wave biosensor is
9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings
the SAW platform into the range useful for clinical diagnosis. Measurement
electronics and microfluidics are easily constructed for acoustic wave
biosensors, such as the Love wave device described here, allowing for robust
platforms for point of care applications for cancer biomarkers in general.
PMID- 28412661
TI - Reliable clinical serum analysis with reusable electrochemical sensor: Toward
point-of-care measurement of the antipsychotic medication clozapine.
AB - Clozapine is one of the most promising medications for managing schizophrenia but
it is under-utilized because of the challenges of maintaining serum levels in a
safe therapeutic range (1-3MUM). Timely measurement of serum clozapine levels has
been identified as a barrier to the broader use of clozapine, which is however
challenging due to the complexity of serum samples. We demonstrate a robust and
reusable electrochemical sensor with graphene-chitosan composite for rapidly
measuring serum levels of clozapine. Our electrochemical measurements in clinical
serum from clozapine-treated and clozapine-untreated schizophrenia groups are
well correlated to centralized laboratory analysis for the readily detected uric
acid and for the clozapine which is present at 100-fold lower concentration. The
benefits of our electrochemical measurement approach for serum clozapine
monitoring are: (i) rapid measurement (~20min) without serum pretreatment; (ii)
appropriate selectivity and sensitivity (limit of detection 0.7MUM); (iii)
reusability of an electrode over several weeks; and (iv) rapid reliability
testing to detect common error-causing problems. This simple and rapid
electrochemical approach for serum clozapine measurements should provide
clinicians with the timely point-of-care information required to adjust dosages
and personalize the management of schizophrenia.
PMID- 28412662
TI - A wireless point-of-care testing system for the detection of neuron-specific
enolase with microfluidic paper-based analytical devices.
AB - Neuron-specific enolase (NSE) had clinical significance on diagnosis, staging,
monitoring effect and judging prognosis of small cell lung cancer. Thus, there
had a growing demand for the on-site testing of NSE. Here, a wireless point-of
care testing (POCT) system with electrochemical measurement for NSE detection was
developed and verified. The wireless POCT system consisted of microfluidic paper
based analytical devices (MUPADs), electrochemical detector and Android's
smartphone. Differential pulse voltammetry (DPV) measurement was adopted by means
of electrochemical detector which including a potentiostat and current-to-voltage
converter. MUPADs were modified with nanocomposites synthesized by Amino
functional graphene, thionine and gold nanoparticles (NH2-G/Thi/AuNPs) as
immunosensors for NSE detection. Combined with MUPADs, the performance of the
wireless POCT system was evaluated. The peak currents showed good linear
relationship of the logarithm of NSE concentration ranging from 1 to 500ngmL-1
with the limit of detection (LOD) of 10pgmL-1. The detection results were
automatically stored in EEPROM memory and could be displayed on Android's
smartphone through Bluetooth in real time. The detection results were comparable
to those measured by a commercial electrochemical workstation. The wireless POCT
system had the potential for on-site testing of other tumor markers.
PMID- 28412663
TI - A facile, rapid and sensitive detection of MRSA using a CRISPR-mediated DNA FISH
method, antibody-like dCas9/sgRNA complex.
AB - Rapid and reliable diagnosis of methicillin-resistant Staphylococcus aureus
(MRSA) is crucial for guiding effective patient treatment and preventing the
spread of MRSA infections. Nonetheless, further simplification of MRSA detection
procedures to shorten detection time and reduce labor relative to that of
conventional methods remains a challenge. Here, we have demonstrated a Clustered
regularly interspaced palindromic repeats (CRISPR)-mediated DNA-FISH method for
the simple, rapid and highly sensitive detection of MRSA; this method uses CRISPR
associated protein 9/single-guide RNA (dCas9/sgRNA) complex as a targeting
material and SYBR Green I (SG I) as a fluorescent probe. A dCas9/sgRNA-SG I based
detection approach has advantages over monoclonal antibody in conventional
immunoassay systems due to its ability to interact with the target gene in a
sequence-specific manner. The detection limit of MRSA was as low as 10 cfu/ml and
was found to be sufficient to effectively detect MRSA. Unlike conventional gene
diagnosis methods in which PCR must be accompanied or genes are isolated and
analyzed, the target gene can be detected within 30min with high sensitivity
without performing a gene separation step by using cell lysates. We showed that
the fluorescence signal of the MRSA cell lysate was more than 10-fold higher than
that of methicillin-susceptible S. aureus (MSSA). Importantly, the present
approach can be applied to any target other than MRSA by simply changing the
single-guide RNA (sgRNA) sequence. Because dCas9/sgRNA-SG I based detection
approach has proved to be easy, fast, sensitive, and cost-efficient, it can be
applied directly at the point of care to detect various pathogens as well as MRSA
in this study.
PMID- 28412664
TI - New model for prediction binary mixture of antihistamine decongestant using
artificial neural networks and least squares support vector machine by
spectrophotometry method.
AB - In the present study, artificial neural networks (ANNs) and least squares support
vector machines (LS-SVM) as intelligent methods based on absorption spectra in
the range of 230-300nm have been used for determination of antihistamine
decongestant contents. In the first step, one type of network (feed-forward back
propagation) from the artificial neural network with two different training
algorithms, Levenberg-Marquardt (LM) and gradient descent with momentum and
adaptive learning rate back-propagation (GDX) algorithm, were employed and their
performance was evaluated. The performance of the LM algorithm was better than
the GDX algorithm. In the second one, the radial basis network was utilized and
results compared with the previous network. In the last one, the other
intelligent method named least squares support vector machine was proposed to
construct the antihistamine decongestant prediction model and the results were
compared with two of the aforementioned networks. The values of the statistical
parameters mean square error (MSE), Regression coefficient (R2), correlation
coefficient (r) and also mean recovery (%), relative standard deviation (RSD)
used for selecting the best model between these methods. Moreover, the proposed
methods were compared to the high- performance liquid chromatography (HPLC) as a
reference method. One way analysis of variance (ANOVA) test at the 95% confidence
level applied to the comparison results of suggested and reference methods that
there were no significant differences between them.
PMID- 28412665
TI - Quantitation of levodopa and carbidopa in rat plasma by LC-MS/MS: The key role of
ion-pairing reversed-phase chromatography.
AB - A simple and selective bioanalytical method was developed for simultaneous
determination of levodopa and carbidopa in rat plasma by LC-MS/MS. Levodopa and
carbidopa are small polar molecules, posing challenges in the development of
selective and efficient chromatography conditions. Perfluoropentanoic acid
(PFPA), a volatile ion-pairing agent, was utilized to enhance chromatographic
characteristics of both compounds in the reversed-phase mechanism. The ion
pairing chromatography played an essential role in mitigating matrix effects and
achieving adequate separation between interfering background peaks and those of
the analytes of interest, especially for levodopa. A 96-well based, automated
liquid-liquid extraction, via the use Hamilton NIMBUS liquid handlers, was
developed. Butyl alcohol, when mixed with ethyl acetate, greatly increased the
recovery of both levodopa and carbidopa. The addition of PFPA further enhanced
recovery for both analytes. Sodium metabisulfite, an antioxidant, was used to
stabilize levodopa and carbidopa in rat plasma. The method was validated in the
ranges of 50-10,000ng/mL and 25-5000ng/mL for levodopa and carbidopa,
respectively, using levodopa-d3 and carbidopa-d3 as internal standards. The
validated method was successfully applied to analyze rat plasma samples from in
life studies.
PMID- 28412666
TI - Student nurses' perceptions of clinical placements in Australian Prison Health
Services: A mixed methods study.
AB - Increasing demands for clinical placements have forced tertiary institutions to
look for alternative placements for third year nursing students. While Prison
Health Services provide an opportunity for nursing students to engage in care of
offender populations with significant chronic illnesses, there has been little
evaluation of such placements. Third year undergraduate nurses (18/46)
participated in a mixed methods study to provide evidence-based research on
students' perceptions of clinical placements in Prison Health Services.
Quantitative and qualitative data were collected via an anonymous survey and
individual interview. Whilst the majority of students valued the opportunity to
increase their knowledge and clinical skills and felt supported by preceptors,
challenges included being psychologically ill-prepared for the physical and
emotional aspects of placement, and witnessing poor attitudes and behaviours of
staff, which impacted on the quality of their experience. Recommendations include
changes to orientation programs and introduction of simulation to help students
feel better prepared and supported during placements in prison settings. Refining
the selection process for placements in this setting will also help to ensure
student suitability for clinical placement in Prison Health Services.
PMID- 28412667
TI - Nurses' perceptions of the impact of Team-Based Learning participation on
learning style, team behaviours and clinical performance: An exploration of
written reflections.
AB - Team-Based Learning (TBL) is a teaching strategy designed to promote problem
solving, critical thinking and effective teamwork and communication skills;
attributes essential for safe healthcare. The aim was to explore postgraduate
student perceptions of the role of TBL in shaping learning style, team skills,
and professional and clinical behaviours. An exploratory descriptive approach was
selected. Critical care students were invited to provide consent for the use for
research purposes of written reflections submitted for course work requirements.
Reflections of whether and how TBL influenced their learning style, teamwork
skills and professional behaviours during classroom learning and clinical
practice were analysed for content and themes. Of 174 students, 159 participated.
Analysis revealed three themes: Deep Learning, the adaptations students made to
their learning that resulted in mastery of specialist knowledge; Confidence, in
knowledge, problem solving and rationales for practice decisions; and
Professional and Clinical Behaviours, including positive changes in their
interactions with colleagues and patients described as patient advocacy,
multidisciplinary communication skills and peer mentorship. TBL facilitated a
virtuous cycle of feedback encouraging deep learning that increased confidence.
Increased confidence improved deep learning that, in turn, led to the development
of professional and clinical behaviours characteristic of high quality practice.
PMID- 28412668
TI - Electroporation of tissue and cells: A three-equation model of drug delivery.
AB - The exposure of the cell membrane to electric pulses of sufficient intensity is
known to result in an increased permeability due to the formation of microscopic
pores. This is electroporation, and it has been implemented to increase the
efficacy of targeted drug delivery. In this study we introduce a novel three
equation model of transport that is able to distinguish the drug uptake in
reversibly electroporated cells from that in irreversibly electroporated cells.
In order to relate the permeability increases and the cell survival to the local
electric field, sigmoidal functions are fit to published experimental data. The
resealing of reversibly electroporated cells is also considered. A numerical
study is presented that considers two different electrode configurations with
different initial drug distributions. This model is able to capture the existence
of an optimal applied voltage, above which any increases in voltage act to
decrease the total drug delivery to the surviving cells, illustrating the
competing influences of increased cell permeability and decreased cell survival.
PMID- 28412669
TI - Measurement of frontal lobe volume and thalamic volume in fetuses with congenital
heart disease at different gestational weeks using three dimensional ultra
sonography and its clinical value.
AB - Our study aimed to investigate the measurement of frontal lobe volume and
thalamic volume in fetuses with congenital heart disease (CHD) at different
gestational weeks using three dimensional (3-D) ultrasonography and its clinical
value. Then, 238 pregnant women who received obstetric ultrasonography in
ultrasound department of Internal Medicine of our hospital were enrolled between
March 2013 to April 2014. In this study, 85 fetuses were diagnosed to develop CHD
by prenatal fetal echocardiography, and the other 153 fetuses were normal.
Frontal lobe volume, thalamic volume and cerebral blood flow was determined by
color Doppler ultrasonic diagnostic apparatus (type: GE Voluson E8). The level of
MCA-PI and CPR in CHD fetus group performed significantly lower than that in
normal fetus group (P<0.05), but the level of UA-PI performed significantly
higher than that in normal fetus group (P<0.05). When gestational age <30 weeks,
there was no significant difference in thalamic volume and frontal lobe volume
between the two groups (P<0.05); when gestational age <30 weeks, the level of CHD
fetus group performed significantly lower thalamic volume and frontal lobe volume
than that in normal fetus group (P<0.05). When gestational age <30 weeks, there
was no significant difference in BPD, HC, and GA between the two groups (P<0.05);
when gestational age <30 weeks, the level of BPD, HC and GA in CHD fetus group
performed significantly lower than that in normal fetus group (P<0.05). If
gestational age <30 weeks, CHD performed a small impact on fetal frontal lobe
volume and thalamic volume; if gestational age <30 weeks, the level of frontal
lobe volume and thalamic volume in fetuses with CHD performed significantly lower
than that in normal fetuses.
PMID- 28412670
TI - Influences of granulocyte growth factor in uterine perfusion on pregnancy outcome
of patients with failure of embryo implantation for unknown reason.
AB - To investigate the influence of granulocyte growth factor in uterine perfusion on
the pregnancy outcome of patients with failure of embryo implantation for unknown
reason. Then, 68 patients with failure of embryo implantation for unknown reason
were enrolled in our hospital from November 2013 to February 2015, which were
divided into observation group and control group by random (34 patients in each
group). Patients in observation group received basic treatment for granulocyte
growth factor in uterine perfusion on the next day, while patients in control
group received basic treatment with placebo. Then, endometrial preparation,
adverse reaction and pregnancy outcome of patients were compared between the two
groups. Comparing the endometrial preparation and average endometrial thickness
of patients in control group (9.87+/-2.12) with those in observation group
[(9.87+/-2.12), there is no significant difference (P<0.05). After treatment,
patients in both groups performed diabetes, hypertension and other pregnancy
complications without difference of statistical significance (P<0.05). The embryo
implantation rate and clinical pregnancy rate of patients in observation group
were significantly higher than those in control group [(82.35%) and (44.12%) vs
(52.94%) and (17.65%)]. Moreover, the live birth rate of patients in observation
group performed significantly higher than that in control group [(41.18%) vs
(14.71%)] with significant difference (P<0.05). By taking treatment of
granulocyte growth factor, patients with failure of embryo implantation can
effectively improve clinical pregnancy rate and embryo implantation rate without
severe complication. Therefore, treatment of granlocyte growth factor can improve
the pregnancy outcome of patients.
PMID- 28412671
TI - Role of SDF-1 and CXCR4 in the proliferation, migration and invasion of cervical
cancer.
AB - This study was to investigate the role of stromal cell-derived factor 1 (SDF-1)
and its corresponding receptor CXCR4 in the proliferation, migration and invasion
of cervical cancer HeLa cells. CXCR4 expression in HeLa cells was measured by
flow cytometry and Western Blot. Role of SDF-1 and CXCR4 in the HeLa cells
proliferation was measured by MTT. Role of SDF-1 and CXCR4 in the migration and
invasion of HeLa cell was measured by Boyden chamber. High expression of CXCR4
was observed on the surface of HeLa cells. Proliferation ability of HeLa cells
was significantly increased after SDF-1 stimulation, which showed dose-dependent
manner. After knock-down of CXCR4 expression by RNAi, SDF-1-stimulated HeLa cells
proliferation was significantly blocked (P<0.05). SDF-1 can induce migration and
invasion of Hela cells, SDF-1-stimulated HeLa cells migration and invasion was
significantly blocked (P<0.05) after knock-down of CXCR4 expression by RNAi. High
expression of surface CXCR4 plays an important role in the proliferation,
migration and invasion of HeLa cells.
PMID- 28412672
TI - Relationship between Alzheimer's disease and mitochondria coenzyme II Gene.
AB - We aimed to investigate the relevance between Alzheimer's disease (AD) and gene
mutations of mitochondrial cytochrome oxidase subunit III (COX3) and coenzyme II
(ND2), and to provide genetic markers for the diagnosis of Alzheimer's disease
(AD) and further provide some feasible basis for preventive treatment. Polymerase
chain reaction-restriction fragment length polymorphism technique was used, and
genotypes and gene frequencies were detected in 60 patients with Alzheimer's
disease (AD), who meet the ICD-10 diagnostic criteria (AD group), 10 AD families
and 60 normal old people (control group). (1) Gene variation on nt5460 gene locus
of mitochondria ND2 of the patient group is G->A, and the variation rate is
13.3%, P=0.006 < 0.05. Gene variation G->A of the patient group perfomred
statistical significance. (2) In the families, it is also found that in the gene
variation of G->A, the variation rate is 33.3%, P > 0.05. There is obvious gene
variation in the families, but this variation does not perform statistical
significance. (3) There is no gene variation on nt9861 gene locus of mitochondria
COX3 of the patient group. Gene variation of T->C is not found both in the
patient group and the control group. There is possible a gene mutation of G->A on
nt5460 gene locus of mitochondria ND2 of the AD patients. Although gene mutation
of G->A is found in the families, it performed no statistical significance. At
the same time, it is found that there is no relation between AD patients and Gene
variation of T->C on nt9861 gene locus of mitochondria COX3.
PMID- 28412673
TI - Effect of controlled hypotension on myocardial ischemia marker in eye-nose
related surgery.
AB - We aimed to investigate the effect of different controlled hypotension levels on
myocardial enzymes and myocardial ischemia protein in elderly hypertension
patients, and then provide clinical evidence of suitable controlled hypotension
level for them. Then, 45 elderly hypertension patients received elective eye-nose
related surgery with nasal endoscope, who were randomly and evenly divided into
three groups, including A, B and C groups, with mean arterial pressure (MAP)
decreased by 20%, 30% and 40% respectively. The change of myocardial enzymes,
myocardial ischemia modified albumin, score of surgical field quality and 12-lead
electrocardiogram at different perioperative points were recorded. Then operative
time, urine output and postoperative adverse complications of the patients were
recorded too. Myocardial enzymes of group C were higher than that of both group A
and B at T4, T5 points (p<0.05); Myocardial ischemia modified albumin of group C
were higher than that of group A and B at T2, T3, T4 and T5 points (p<0.05); The
score of surgical field quality of group A were higher than that of group B and C
(p<0.05); Operation time of group C is less than that of group A and B (p< 0.05);
The change of ST segment in group C is more obvious than that in group A and B
(p<0.05); The incidence of adverse complications of group C is higher than that
of group A and B (p<0.05). Controlled hypotension with MAP reduced by 30% brings
minimum myocardial damage and fewer complications, while meeting the demand of
surgical field. Thus it is an ideal controlled hypotension level and can be used
for elderly hypertension patients safely.
PMID- 28412674
TI - Analysis of relevant risk factors for intrauterine death of fetuses in the third
trimester of pregnancy.
AB - Our study aimed to explore the relevant risk factors for intrauterine death of
fetuses in the third trimester of pregnancy via a retrospective analysis. Then,
98 pregnant women with intrauterine death of fetuses in the third trimester of
pregnancy were enrolled, who had undergone the induced labor of dead fetuses in
our hospital from January, 2013 to January, 2015. By taking their disease
conditions into considerations, methods of induced labor as softening of cervix
with dinoprostone suppositories and amniotic infusion of ethacridine or oxytocin
were performed, and the timely cesarean section for termination of pregnancy was
performed. After the treatment, a detailed medical history was recorded,
including their family history, past history and conditions of this pregnancy.
Besides, autopsy of dead fetuses and pathological examinations were performed as
well as chromosome examinations of the placenta, the umbilical cord and the fetal
membrane in an attempt to identify the relevant factors for causes of death, so
as to do a good job in the post-natal consultation. The induced labor procedures
were successfully performed on all pregnant women, and the investigation of
causes of intrauterine death showed that placental factors were responsible for
the largest proportion of all causes of intrauterine death in single (28
patients), which was 31.82%, including 13 patients with placenta praevia and 13
with placental abruption. The secondary factors were umbilical cord factors,
accounting for 30.68%. Among the factors of pregnant women, gestational
hypertension occurred in 7 patients, accounting for 58.33% of factors of pregnant
women. While among the causes of intrauterine death in twins, umbilical cord
factors were found to be the main causes of death, accounting for 30.00%,
followed by placental factors and factors of pregnant women, which accounted for
20.00%, respectively. Placenta factors, umbilical cord factors and factors of
pregnant women were the main causes of intrauterine death of fetuses in the third
trimester of pregnancy. Therefore, pregnancy tests on time for routine screening
is recommended for pregnant women so as to identify the potential risk factors in
time and actively carry out symptomatic treatment, thereby reducing the chances
of intrauterine death of fetuses and improving the qualities of pregnancy. It is
worth clinical attention.
PMID- 28412675
TI - Paired observation on light-cured composite resin and nano-composite resin in
dental caries repair.
AB - To compare the value of light-cured composite resin with that of nano-composite
resin in dental caries repair. 88 patients taking dental caries repair in our
hospital from May 2014 to April 2015 were selected, and divided into observation
group and control group by coin method with 44 patients in each group. Nano
composite resin was used in observation group, while light-cured composite resin
in control group. Then, the occurrence rates of odontohyperesthesia, aesthetic
satisfaction with dental caries repair and complications were compared between
two groups by visual analogue scale (VAS). The occurrence rate of
odontohyperesthesia in observation group is significantly lower than that in
control group (9.09% (4/44) vs 31.82% (14/44), 6.82% (3/44) vs 22.73% (10/44),
2.27% (1/44) vs 13.64% (6/44)) with difference of statistical significance
(P<0.05) 1 week, 4 weeks, and 8 weeks after repair. VAS score of patients in
observation is significantly lower than that in control group ((2.78+/-0.56)
scores vs (5.22+/-0.76) scores, (2.02+/-0.35) scores vs (4.32+/-0.57) scores,
(1.12+/-0.14) scores vs (2.41+/-0.43) scores) 1 week, 4 weeks, and 8 weeks after
repair. Moreover, the difference in comparison of interactive effects between two
groups, between different time points, and between groups at different time
points has statistical significance (P<0.05). Nano-composite resin can lower the
occurrence rate of odontohyperesthesia in dental caries repair, reduce the pain
of patients, and improve the satisfaction of patients with tooth appearance.
PMID- 28412676
TI - Investigation of sub-health status of neonates in Heping street region (Beijing)
and analysis on related risk factors.
AB - To investigate sub-health status of neonates in Heping Street Region and related
risk factors. Then, 7436 maternal women admitted to hospital in Heping Street
Region, Beijing were enrolled from October 2013 to September 2015, including 293
women, who gave birth to sub-health neonates. Questionnaire survey was conducted
to collect maternal age, education degree, experiences and income, occupation,
life habit, condition in pregnancy, condition in perinatal period, adverse
reaction in pregnancy, etc. Finally, 281 effective questionnaires were regained
with effective regain rate of 95.90%. Compared with the occurrence rate of sub
health neonates between local population and floating population, correlation
analysis and multi-factor Logistic regression analysis were conducted on the
influence factors of sub-health neonates. The occurrence rate of sub-health
neonates among floating population is higher than that among local population
(1.10% (59/2641) V.S. 4.88% (234/4795)) with significant difference (P<0.05).
Correlation analysis showed that the differences in mother's age, family income,
education degree, harmful factors in contact environment, prenatal care, history
of adverse pregnancy, unhealthy metal factor, gestational diabetes, diseases
history in pregnancy, drug history in pregnancy, sexually transmitted disease,
pregnancy hypertension, premature rupture of fetal membranes, and circular of
umbilical cord performed statistical significance (P<0.05). Moreover, mother's
age, premature rupture of fetal membranes, disease history in pregnancy, drug
history in pregnancy and pregnancy hypertension are the influence factors for the
risk of sub-health neonates, while high family income and healthcare in pregnancy
are protective factors from the risk of sub-health neonates. All of these
differences showed statistical significance (P<0.05). The occurrence of sub
health neonates among floating population is higher than that among local
population. Mother's age, premature rupture of fetal membranes, disease history
in pregnancy, drug history in pregnancy, and pregnancy hypertension are major
risk factors of sub-health neonates. Therefore, these results help us to take
corresponding measures to improve the quality of newly-born population.
PMID- 28412677
TI - Differential analysis of clinical efficacy on patients with serious infection in
ICU by different meropenem regimens.
AB - To investigate the difference in clinical efficacy and safety of different
meropenem regimens on patients with serious infection in ICU. Then, 228 patients
with serious infection in ICU were divided by random into control group
(intermittent administration in 1000mg/30min single dose) and research group
(continuous administration in 200mg/10min +800mg/180min), respectively. The blood
concentration of meropenem were recorded in two groups at different time points,
and difference in treatment effectiveness, iconographic effectiveness, bacterial
eradication rate, 28-day survival rate and many other clinical scoring indices
(SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212
patients completing the whole research, including 104 patients in research group
and 108 patients in control group. The difference in treatment effectiveness
(77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day
survival rate (86.5% vs 64.8%) between two groups performed statistical
significance (P<0.05). However, the difference in bacterial eradication rate
(48.0% vs 46.3%) performed no statistical significance. Eight hours later, the
difference in average blood concentration between two groups (9.61+/-3.63MUg/ml
vs 1.5+/-0.51MUg/ml) showed statistical significance. Moreover, the difference in
clinical scoring indices except APACHE II score between two groups performed
statistical significance. It was helpful to maintain the blood concentration of
meropenem by extending the transfusion time. Therefore, it could increase the
clinical cure rate and 28-day survival of patients with serious infection in ICU,
improve clinical indices, and reduce the usage amount of antibiotics.
PMID- 28412678
TI - Clinical study of lung-supplementing and stasis-dissolving decoction (Bufei Huayu
Tang) combined with gefitnib for treatment of advanced non-small cell lung
cancer.
AB - To investigate the clinical efficacy and drug safety of Lung-Supplementing and
Stasis-Dissolving Decoction (Bufei Huayu Tang) combined with gefitnib for
treatment of advanced non-small cell lung cancer (NSCLC). Then, 80 patients with
advanced NSCLC hospitalized in Ruikang Hospital Affiliated to Guangxi University
of Chinese Medicine were included, and were double-blindly randomized into 4
groups: control group (gefitinib alone 250mg, once daily), low-dose group
(100mL/day), middle-dose group (150mL/day) and high-dose group (200mL/day)
treated with different doses of Bufei Huayu Tang besides gefitinib. Clinical
efficacy, life quality change before and after treatment, ECOG score, survival
time and incidence of adverse drug reaction were compared. ECOG score in middle
dose group after treatment was significantly higher than other groups (P<0.05).
Total efficiency of 4 groups was respectively 15%, 20%, 55% and 25%, and total
efficiency in middle-dose group was significantly higher than that in other
groups (P<0.05). According to TCM syndrome score, the improvement in middle-dose
group was significantly better than that in other groups (P<0.05). Incidence of
adverse drug reaction in high-dose group was significantly higher than that in
other 3 groups (P<0.05). Self-designed Bufei Huayu Tang combined with gefitinib
for NSCLC has a satisfactory clinical efficacy and high drug safety. Decoction
dose needs more attention.
PMID- 28412679
TI - Epidemic characteristics of main infectious diseases in Yantai city between 2010
and 2012 and prevention strategy research.
AB - To investigate the epidemic characteristics and prevention strategies of main
infectious diseases. From 2010 to 2012, 23 notifiable diseases were reported in
Yantai with average reported cases of 17,376. The morbidity was the highest in
2012 and the lowest in 2011. The accumulated death toll was 101 with the highest
death rate in 2011 and the lowest in 2012. Major class A and B infectious
diseases included viral hepatitis, phthisis, syphilis, clap and dysentery. The
major class C infectious disease was hand-foot-and-mouth disease every year. The
distribution of transmission routes of HIV/AIDS among patients with HIV and AIDS
in Yantai were investigated. The overall condition of phthisis in Yantai showed
stable with slight decrease. The occurrence rate of phthisis every season had
fluctuation with higher rate in middle two seasons and lower rate at the
beginning and end. The major type of viral hepatitis was still hepatitis B.
Patients with hand-foot-and-mouth disease were children under 5 years old
accounting for 90.56%, mainly reported in May, June, July and August. At present,
the condition of plague prevention for infectious diseases in Yantai is not
optimistic with both new and old infectious diseases.
PMID- 28412680
TI - Study on effect of Combivent combined with glucocorticoids in the treatment of
patients with AECOPD.
AB - We observed the effect of Combivent combined with glucocorticoids in the
treatment of patients with AECOPD to explore a better drug treatment for AECOPD.
The clinical observation of two clinical curative effective was carried out.
Firstly, 100 patients were equally divided into treatment group and control
group, who were given basic treatment. The control group was treated with
inhalation of salbutamol sulfate and the other was with inhalation of Combivent
and glucocorticoid. The clinical effect, dyspnea score, PaO2, PaCO2 and pulmonary
function index were observed and compared. The second, 100 patients with AECOPD
were divided into the conventional group, the short range group and the long
range group, all of that were treated with inhalation of Combivent. The short and
the long were treated with glucocorticoid for 7d and 15d.Pulmonary function index
was monitored at sixth and fifteenth days after treatment. The incidence of
AECOPD was compared with the incidence of complication. Firstly, after 10 days of
treatment, the treatment group's total efficiency, dyspnea score, PaO2, PaCO2,
were significantly better than the control group and the treatment in the two
groups after the above indexes were significant better than those before
treatment. The differences were statistically significant (P<0.05). The second
time, the short and the long's VC, FVC, FEV1 were higher than the conventional,
the recurrence rate was decreased, the incidence of complications in the short
was significantly lower than that in the long and the difference was
statistically significant (P<0.05). The effect of Combivent combined with
glucocorticoid was exactly and the short's complication was low, which is worth
to be popularized.
PMID- 28412681
TI - Research on in vitro release of Isoniazid (INH) super paramagnetic microspheres
in different magnetic fields.
AB - To explore in vitro release rules of isoniazid (INH) when Isoniazid Super
paramagnetic Iron Oxide Microspheres (ISPIOM) are subject to no external magnetic
field, applied mechanical magnetic field and scillating magnetic field. ISPIOM
was prepared by using the spray drying method; Isoniazid contented in the
microspheres was determined, the drug loading capacity and encapsulation
efficiency were calculated. Release of isoniazid in the microspheres was
determined respectively under the effect of no external magnetic field, applied
mechanical magnetic field and oscillating magnetic field, to explore the release
rules. In solution with pH=7.4 PBS, microspheres featured 8-hour sustained
release under the effect of magnetic field, the released rate of the microspheres
is accelerated,. In solution with pH=3 PBS, microspheres release faster and could
realize the fastest completion of release in 2 hours under the effect of
oscillating magnetic field. To join the external magnetic field in different
point time to can't affect the release, under pH=3 of medium, ISPIOM release
faster; under the effect of magnetic field, the released rate of the microspheres
is accelerated, and the longer effect of magnetic field, the faster release.
Oscillating magnetic field can make ISPIOM within a certain period of time, get
ideal release curve, so as to achieve good control release effect.
PMID- 28412682
TI - Application frequency and therapeutic effect of Astragalus in treating ischemic
cerebrovascular disease.
AB - In recent years, Traditional Chinese Medicine (TCM) therapy has achieved
substantial progress and development, playing an important role in clinical
practice. In this paper, to explore the therapeutic effect of Astragalus in
treating ischemic cerebrovascular disease, 2687 patients with ischemic
cerebrovascular disease who had been treated with Astragalus therapy from Jan
2014-Oct 2015 were selected as the research objects. Through retrospective
analysis of their medical records, we analyzed the application frequency of
Astragalus using quantitative method of information, and conducted specific
analysis on the therapeutic effect of Astragalus after fully surveyed patients'
physical conditions after treatment. Results show that in the treatment of
ischemic cerebrovascular disease by TCM, Astragalus is of high application
frequency and sound therapeutic effect, which is deserved to be applied and
promoted in clinical practices.
PMID- 28412683
TI - Safety in Treating Primary Acute Angle-closure Glaucoma under High Intraocular
Pressure by Compound Trabeculectomy.
AB - In clinical practice, Primary Acute Angle-closure Glaucoma (APACG) is a common
disease with an increasing incidence rate and blind rate, and has attracted
attention of medical researchers. When a patient suffers both primary acute
glaucoma and high tension glaucoma, drug therapy can achieve limited efficacy,
and operative treatment is necessary on this occasion. This research mainly
explored the safety in treating high tension APACG by compound trabeculectomy,
and observed the clinical treatment effect and incident rate of postoperative
complications after compound trabeculectomy. The compound trabeculectomy can
effectively control the intraocular pressure and decrease the incident rate of
postoperative complications, accelerating the rehabilitation of patients.
PMID- 28412684
TI - Clinical application analysis of continuing nursing in nursing service for
diabetic patients.
AB - : The research is to establish a Continuing Nursing Project after discharge which
conforming to the actual conditions of our country and explore whether such
Continuing Nursing Project could effectively improve therapy compliance and blood
glucose control of diabetic patients. METHODS: mainly analyzing pathological
mechanisms of diabetic patients and exploring the clinical effect and the
complication after implementing Continuing Nursing to patients. RESULTS: after
implementing Continuing Nursing, the diabetic patients could be better at
controlling their diet, the drug usage rate and exercise rate have been improved
significantly, complication rate have been decreased and the clinical effect is
remarkable. CONCLUSION: the application of Continuing Nursing in the nursing
service for diabetic patients, which could effectively improve living quality and
clinical symptoms of patients, deserves to be popularized.
PMID- 28412685
TI - TCM comprehensive nursing intervention to pathological jaundice on neonate.
AB - Pathological Jaundice on neonate differs from that of physiologic jaundice. They
perform differently on clinical cases, which is an effective way to distinguish
them. There are many causes for pathological jaundice, common ones include
hemolytic jaundice, infectious jaundice, obstructive jaundice, breast-feeding
jaundice, etc. Clinically proven that pathological jaundices has significant
differences in symptoms. This brings problems to its treatment and nursing. In
recent years, TCM comprehensive nursing shows great results in treating process.
Therefore, this paper take 2000 cases to make a thorough analysis for the actual
clinical effects of TCM comprehensive nursing on pathological jaundice on
neonate.
PMID- 28412686
TI - Analysis of application of docetaxel combined therapy scheme in treating advanced
head and neck neoplasm.
AB - Docetaxel is a semi-synthetic taxoid anti-cancer drug, which can basically freeze
intracellular skeleton that is composed of microtubules, so as to inhibit cell
division. Under normal condition, Docetaxel can make microtubule in a cell cycle
follow the rule of first polymerization and then depolymerization. Moreover,
docetaxel can further promote the microtubule polymerization while inhibiting
cell depolymerization, so as to prevent cells division, lead to cancer cells
death, and improve the therapeutic efficiency of tumor and cancer. However, as a
newly developed drug, docetaxel's specific clinical effect has not been fully
verified yet. Therefore, in this research, 2000 patients of advanced head and
neck neoplasm were selected as research objects, which were treated with
docetaxel combined with DDP and fluorouracil. By observing indexes such as
patient's condition, complication condition, and life quality, the clinical
effect of docetaxel combined therapy scheme in treating head and neck neoplasm
was analyzed. Results show that such therapy scheme is of sound therapeutic
effect and high application value.
PMID- 28412687
TI - Application of tegafur gimer, docetaxel and carboplatin in head and neck squamous
cell carcinoma therapy.
AB - Squamous cell carcinoma, in the clinical manifestation, is a form of cancer
derived from lesions of keratinocytes of epidermis or accessories such as
sebaceous ducts, hair follicles, sweat glands, etc. The disease is more common in
older men, with prone locations at patients' scalp, face, neck and arms and other
exposed parts. Head and neck squamous cell carcinoma (HNSCC) causes a serious
impact on patients' daily life, making patients suffer from double blow in mental
and physical aspects and reducing patients' life quality. To find effective
treatment method for HNSCC, our hospital studies clinical effects of combination
therapy of tegafur gimer, docetaxel and carboplatin for the disease. By way of
grouping research, therapeutic effect of such treatment and adverse reactions
were assessed and analyzed. The study clearly and fully confirms effectiveness of
combination therapy of tegafur gimer, docetaxel and carboplatin for HNSCC.
PMID- 28412688
TI - Clinical research of treating tuberculous respiratory failure by sequential
mechanical ventilation.
AB - Tuberculosis is kind of common chronic infectious disease, of which the
pathogenic bacterium is mainly Mycobacterium tuberculosis (MTB). One who is
suffering severe tuberculosis may be ended with cardio-pulmonary function damage
or cardio-pulmonary failure. This disease is of higher risks of complications or
even high death rate, which is seriously challenging people's health and life.
When a tuberculosis patient is accompanied with respiratory failure, which means
the disease has developed into the late stage, on this occasion the optimal
treatment program is to use mechanical ventilation to improve the respiratory
failure condition. This research mainly explored the clinical effect of treatment
of tuberculous respiratory failure by sequential mechanical ventilation, and
observed clinical treatment effect, patients' basic conditions, condition of VAP
and deterioration-in-death condition after sequential mechanical ventilation.
PMID- 28412689
TI - Simple, rapid and highly sensitive HPLC method for measurement of Lamotrigine in
human plasma and its clinical applications.
AB - Spikes in Lamotrigine concentrations levels and associated clinical toxicity may
occur unpredictably. This study describes the development and validation of a
simple, more rapid, highly sensitive and economical method for measuring
Lamotrigine (LTG) concentration levels in human plasma using HPLC-UV and its
clinical applications. Analyte from plasma was extracted with methanol (protein
precipitation) and separated on the analytical column Diamonsil C18 (150mm*4.6mm,
5MUm) Waters-Milford, MA, United States. Mixture of 0.1% Trifluoroacetate and
Methanol used as mobile phase in a 59:41 volume/volume mixture with an isocratic
flow rate of 1.5 ml/min and wavelength was adjusted to 260nm. Standard curve of
lamotrigine showed good linearity over the range of 1.0-50MUg/mL (r2=0.9961) and
LLOQ was 1.0MUg/ml. The Specificity, Recovery, Accuracy, Stability, Robustness
and RSDs for both intraday and interday precision were within acceptable limits.
The highly sensitive HPLC assay for determination of LTG in human plasma was
demonstrated, validated and applied in Therapeutic Drug Monitoring (TDM) of sixty
seven epilepsy patients who were using LTG. The proposed method can be easily
applied in routine Therapeutic monitoring of LTG, Besides TDM, stated method can
be also very useful for Bioequivalence studies, Pharmacovigilance and
Pharmacokinetics studies.
PMID- 28412690
TI - Epidemiological characteristics and clinical features of sporadic viral hepatitis
E (HEV).
AB - OBJECTIVE: The study aims to analyze the epidemiological characteristics and
clinical features of sporadic viral hepatitis E. METHODS: The 1,000 cases of
sporadic viral hepatitis E patients treated in 20 hospitals from May 2013 to May
2016 were selected as research subjects, with their clinical data retrospectively
analyzed. RESULTS: (1) Epidemiological characteristics: Seen from the disease
time, the 1,000 patients have morbidity throughout the year, but morbidity in hot
and rainy summer is significantly higher than other seasons, there exists
statistically difference in comparison between the groups (P<0.05); sporadic
viral hepatitis E has no family aggregation; male morbidity is greater than
female. In the study, there were male 782 cases, 218 female cases, with
male/female ratio at 3.6: 1; morbidity was 13.7% (137/1000) for patients under
18, 62.9% (629/1000) for patients aged 18-60, 23.4% (234/1000) for patients over
60; there were 692 cases of simplex hepatitis E (simplex infection), 308 cases of
hepatitis E complicated with chronic liver disease (super infection), of which,
complicated viral hepatitis B took up the majority. (2) Clinical features: In the
early stage, patients had symptoms of fever, stuffy nose, sore throat; 784
(78.4%) patients had jaundice during illness; 527 (52.7%) patients had loss of
appetite, nausea and other gastrointestinal symptoms; ALT, AST of patients with
hepatitis E plus posthepatitic cirrhosis were significantly lower than patients
with simplex infection (all P<0.01); total bilirubin in patients over 60 was
significantly higher than that of young and middle-aged patients, statistical
difference in statistical analysis was (P <0.05); in the study, 274(27.4%)
patients had complications, complication probability of patients aged over 60 was
higher than young and middle-aged patients, difference comparison was
statistically significant (P<0.05); complication probability of super infected
patients was higher than those with simplex infection (P<0.01). All the patients
underwent liver protection, jaundice removal and other symptomatic treatments,
achieving good treatment effect: 315 cases were cured, 678 cases had improved
condition, 7 cases died. CONCLUSION: There exists obvious correlation between
morbidity of sporadic viral hepatitis E and season, gender and age; once sicken,
one needs to take early symptomatic treatment, to avoid more severe damage to
liver function.
PMID- 28412691
TI - Clinical effect of treatment on elderly chronic obstructive pulmonary disease
combined with pulmonary tuberculosis.
AB - OBJECTIVE: To explore and analyze the clinical therapeutic schedule of elderly
chronic obstructive pulmonary disease combined with pulmonary tuberculosis.
METHOD: This clinical research analysis chooses the 2000 patients suffered
elderly chronic obstructive pulmonary disease combined with pulmonary
tuberculosis treated in the hospital during June of 2014 and June of 2015 as the
object of observation. These 2000 cases are randomly divided into experimental
group and control group. The patients in the control group are treated with the
common method; based on the common method, those in the experimental group are
treated with the atomization inhalation treatment of compound ipratropium bromide
and budesonide and have rifampicin. The clinical effects of two groups are
observed and contracted. RESULTS: The clinical treatment, CRP and other clinical
evaluation indexes of experimental group are superior to the control group
(P<0.05). There are significant differences between two groups with the
statistical significance. CONCLUSION: The atomization inhalation treatment of
compound ipratropium bromide and budesonide and rifampicin are implied into the
elderly chronic obstructive pulmonary disease combined with pulmonary
tuberculosis that can remarkably improve the effect of clinical treatment has
higher clinical promotional value.
PMID- 28412692
TI - Review-Research on the physical training model of human body based on HQ.
AB - Health quotient (HQ) is the newest health culture and concept in the 21st
century, and the analysis of the human body sports model is not enough mature at
present, what's more, the purpose of this paper is to study the integration of
the two subjects the health quotient and the sport model. This paper draws the
conclusion that physical training and education in colleges and universities can
improve the health quotient, and it will make students possess a more healthy
body and mind. Then through a new rigid body model of sports to simulate the
human physical exercise. After that this paper has an in-depth study on the
dynamic model of the human body movement on the basis of establishing the matrix
and equation. The simulation results of the human body bicycle riding and pole
throwing show that the human body joint movement simulation can be realized and
it has a certain operability as well. By means of such simulated calculation, we
can come to a conclusion that the movement of the ankle joint, knee joint and hip
joint's motion law and real motion are basically the same. So it further verify
the accuracy of the motion model, which lay the foundation of other research
movement model, also, the study of the movement model is an important method in
the study of human health in the future.
PMID- 28412694
TI - The sting.
PMID- 28412693
TI - Feeding Angptl4-/- mice trans fat promotes foam cell formation in mesenteric
lymph nodes without leading to ascites.
AB - Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting
LPL. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces the risk
of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic
management of dyslipidemia and atherosclerosis is hampered by the observation
that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation
in the mesenteric lymph nodes (MLNs). In mice these pathological events
exclusively unfold upon feeding a high saturated FA diet and are followed by an
ultimately lethal pro-inflammatory response and chylous ascites. Here, we show
that Angptl4-/- mice fed a diet rich in trans FAs develop numerous lipid-filled
giant cells in their MLNs, yet do not have elevated serum amyloid and
haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a
saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate,
markedly increased markers of inflammation and the unfolded protein response,
whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the
opposite effect. In conclusion, trans and saturated FAs have very distinct
biological effects in macrophages. Furthermore, lipid accumulation in MLNs is
uncoupled from activation of an acute-phase response and chylous ascites,
suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
PMID- 28412696
TI - PDGF-D is a ligand for NRP1.
PMID- 28412697
TI - Sema3A signalling requires CRMP1 and Nav1.7.
PMID- 28412698
TI - PRODH-ing senescence along.
PMID- 28412699
TI - Neural activity and synaptic pH.
PMID- 28412700
TI - Takayasu Arteritis and Spondyloarthritis: Coincidence or Association? A Study of
14 Cases.
AB - OBJECTIVE: Spondyloarthritis (SpA) and Takayasu arteritis (TA) are 2 chronic
inflammatory diseases; their coexistence in a single patient is uncommon. The
aims of our study were to describe clinical features of patients having SpA
associated with TA and to identify some characteristics of the types of patients
with SpA associated with TA. We also analyzed treatments used in this context.
METHODS: This French multicenter retrospective survey called for observations on
behalf of the Club Rhumatismes et Inflammations, with a standardized
questionnaire established by the investigators. RESULTS: We included 14 patients
(women: 10/14; median age at SpA diagnosis: 43.5 yrs, ranging from 19 to 63).
Subtypes of SpA were ankylosing spondylitis (n = 11), psoriatic arthritis (n =
2), and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (n = 1).
HLA-B27 was positive in 3 cases, negative in 9, and unknown in 2. SpA was
diagnosed before TA in 13 cases. Imaging findings compatible with the diagnosis
of TA were found with computed tomography (11/14) and/or Doppler ultrasound
(10/14). Laboratory tests showed increased acute-phase reactants in all cases (C
reactive protein >= 25 mg/l in 71% of the cases). All patients except 1 received
corticosteroids and 7 were treated with anti-tumor necrosis factor (anti-TNF).
CONCLUSION: Association of SpA and TA is rare but probably not coincidental.
Peripheral pulse palpation and vascular auscultation should be systematic and are
the first indicators of TA in patients with SpA. Moreover, increased acute-phase
reactants during SpA followup should lead to search for TA. Finally, there are
therapeutic implications because anti-TNF are efficient in SpA and might be
efficient in TA.
PMID- 28412701
TI - Association Between Medications and Herpes Zoster in Japanese Patients with
Rheumatoid Arthritis: A 5-year Prospective Cohort Study.
AB - OBJECTIVE: To investigate the association between medications and herpes zoster
(HZ) in patients with rheumatoid arthritis (RA) given biological disease
modifying antirheumatic drugs (bDMARD) or conventional synthetic DMARD in the
clinical setting during 5 years using the Registry of Japanese Rheumatoid
Arthritis Patients on Biologics for Longterm Safety (REAL) database. METHODS: We
calculated the crude incidence rate (IR) of HZ treated with systemic antiviral
medications in 1987 patients from the REAL database. To estimate the association
between HZ and medications, a nested case control study was performed with 1:5
case-control pairs matched for age, sex, observation start year, and comorbidity
(HZ case group, n = 43; control group, n = 214). We calculated OR and 95% CI of
the use of bDMARD, methotrexate (MTX), and corticosteroids for the occurrence of
HZ using a conditional logistic regression analysis. RESULTS: The median patient
age was 60.0 years, female proportion was 81.5%, and median disease duration was
6.0 years. The crude IR (95% CI) of HZ was 6.66 (4.92-8.83)/1000 person-years.
The OR (95% CI) of medication use were 2.28 (1.09-4.76) for tumor necrosis factor
inhibitor (TNFi) and 1.13 (1.03-1.23) for oral corticosteroids dosage (per 1 mg
prednisolone increment), both of which were significantly elevated. The OR of non
TNFi and MTX usage were not elevated. CONCLUSION: TNFi use and higher
corticosteroids dosage were significantly associated with HZ in Japanese patients
with RA in the clinical setting.
PMID- 28412702
TI - Case-control Study on Dactylitis, Enthesitis, and Anterior Uveitis in
Spondyloarthritis Associated with Inflammatory Bowel Diseases: Role of Coexistent
Psoriasis.
AB - OBJECTIVE: To evaluate the frequency of dactylitis, enthesitis, and anterior
uveitis (AU) in spondyloarthritis (SpA) associated with inflammatory bowel
disease (IBD-SpA) compared with other SpA, and to assess the role of associated
psoriasis in the occurrence of dactylitis and enthesitis. METHODS: In a 12-month
case-control study, the frequency of dactylitis and enthesitis in 29 patients
with ulcerative colitis (UC) and 59 with Crohn disease (CD) who satisfied the
Spondyloarthritis international Society criteria for axial or peripheral SpA was
compared with 176 controls, including 97 (55.1%) with psoriatic arthritis (PsA),
47 (26.7%) with ankylosing spondylitis (AS), and 32 (18.2%) with nonradiographic
axial SpA (nr-axSpA). The occurrence of these features in IBD-SpA with and
without psoriasis was also evaluated. RESULTS: Axial, peripheral, or mixed
involvement was observed in 46 (52%), 29 (33%), and 13 (15%) patients,
respectively; and 14/88 (16%) had psoriasis. Dactylitis was recorded in 4/88
patients (4.5%) with IBD-SpA and in 30 controls (17.4%; p = 0.008), enthesitis in
16 cases (18.1%) and in 78/176 controls (44.3%; p < 0.001), and AU in 3 patients
(3.4%) with IBD-SpA and in 26 controls (14.7%; p = 0.01). No significant
differences were found between patients with UC-SpA and those with CD-SpA.
Dactylitis and enthesitis were significantly more common in patients with IBD-SpA
who also had psoriasis compared to those without skin disease (p = 0.009 and
0.003, respectively). CONCLUSION: Dactylitis, enthesitis, and AU are
significantly less frequent in IBD-SpA compared with other types of SpA. Given
the frequent association of psoriasis and IBD, overlooking coexistent skin
disease may lead to overestimating the frequency of these features.
PMID- 28412703
TI - Self-reported Diagnosis of Rheumatoid Arthritis or Ankylosing Spondylitis Has Low
Accuracy: Data from the Nord-Trondelag Health Study.
AB - OBJECTIVE: Self-reported diagnoses of inflammatory arthritis are not accurate.
The primary study aim was to ascertain self-reported diagnoses of rheumatoid
arthritis (RA) and ankylosing spondylitis (AS) in the Norwegian population-based
Nord-Trondelag Health Study (HUNT) using hospital case files. The secondary aim
was to provide updated estimates of the prevalence and incidence of RA and AS.
METHODS: All inhabitants >= 20 years old from the county of Nord-Trondelag were
invited. Data from 70,805 unique participants from HUNT2 (1995-1997) and HUNT3
(2006-2008) were included. For participants who self-reported RA or AS, case
files from all 3 hospitals in the catchment area were evaluated using
standardized diagnostic criteria. RESULTS: Of 2703 self-reported cases of RA,
19.1% were verified in hospital files. Of 1064 self-reported cases of AS, 15.8%
were verified. Of 259 cases self-reporting both RA and AS, 8.1% had RA and 5.4%
had AS. Overall, a self-report of 1 or both diagnoses could not be verified in
82.1%, including 22.8% with insufficient information or no case file. The
prevalence of RA was 768 (95% CI 705-835) per 100,000. The incidence of RA from
HUNT2 to HUNT3 was 0.48 (0.41-0.56) per 1000 per year. The prevalence of AS was
264 (228-305) per 100,000. The incidence of AS from HUNT2 to HUNT3 was 0.19 (0.15
0.24) per 1000 per year. CONCLUSION: Self-reported diagnoses of RA and AS are
often false-positive. The prevalence and incidence of RA were comparable to
reports from similar populations. The incidence of AS was higher than previously
reported in a mixed population from Norway.
PMID- 28412704
TI - Structural Validity of the Rheumatology Attitudes Index in Systemic Sclerosis:
Analysis from the UCLA Scleroderma Quality of Life Study.
AB - OBJECTIVE: To evaluate the structural validity of the Rheumatology Attitudes
Index (RAI), a widely used measure of rheumatic disease-related helplessness in
patients with systemic sclerosis (SSc). METHODS: Patients with physician
confirmed SSc from the University of California, Los Angeles (UCLA) Scleroderma
Quality of Life Study (n = 208) received clinical examinations and completed self
report questionnaires. The structural validity of the RAI was examined through
confirmatory and exploratory factor analysis (CFA/EFA). RESULTS: A tenable factor
structure was not identified through CFA or EFA. CONCLUSION: The present
structural analysis did not support the use of the RAI with SSc patients.
PMID- 28412705
TI - Interferon-alpha for Induction and Maintenance of Remission in Eosinophilic
Granulomatosis with Polyangiitis: A Single-center Retrospective Observational
Cohort Study.
AB - OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized
by frequent relapses following induction therapy. Interferon-alpha (IFN-alpha)
can reverse the underlying Th2-driven immune response and has successfully
induced remission in previous reports. We undertook this study to investigate its
efficacy and safety in patients with EGPA. METHODS: We conducted a retrospective
monocentric cohort study including 30 patients (16 women) with active EGPA under
IFN-alpha treatment. Primary endpoints were remission induction, occurrence of
relapses, prednisolone (PSL) dosage at time of remission, and adverse events.
Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0.
Pulmonary function tests were recorded at baseline and at time of remission.
Health-related quality of life was analyzed by questionnaire at baseline and
following 12 months of treatment. RESULTS: At baseline, the median BVAS was 6
(interquartile range 4-13.5) and remission or partial response was achieved in
25/30 patients. After initiation of IFN-alpha treatment, the median PSL dosages
could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission.
Following remission, 17 relapses (5 major) in 16 patients were observed.
Pulmonary function tests improved and the time of hospitalization decreased.
Adverse events at initiation of treatment were common, but mostly transient.
Severe adverse events occurred during treatment in 4 patients (autoimmune
hepatitis, n = 1; drug-induced neuropathy, n = 3). CONCLUSION: IFN-alpha
treatment results in high rate of remission and maintenance in EGPA with
significant reduction in oral corticosteroids, although reversible adverse events
may occur. IFN-alpha represents an alternative therapeutic option in cases of
refractory to standard treatment.
PMID- 28412706
TI - Endocrine Comorbidities in Patients with Psoriatic Arthritis: A Population-based
Case-controlled Study.
AB - OBJECTIVE: To investigate endocrine comorbidities in patients with psoriatic
arthritis (PsA). METHODS: A retrospective, cross-sectional study was performed
with the database of Clalit Health Services, the largest healthcare provider in
Israel, between 2002 and 2014. Patients with PsA were identified and matched by
age and sex to healthy controls. The following morbidities were analyzed:
hypo/hyperthyroidism, hypo/hyperparathyroidism, hyperprolactinemia, Cushing
disease, Addison disease, diabetes insipidus, diabetes mellitus (DM), pituitary
adenoma, acromegaly, and osteoporosis. Descriptive statistics were applied. The
associations between PsA and endocrine comorbidities were analyzed by univariable
and multivariable analysis. RESULTS: The study included 3161 patients with PsA,
53.4% women, mean age 58.4 +/- 15.4 years, and 31,610 controls. Comparative
analyses yielded higher proportion of hypothyroidism (12.7% vs 8.6%, p < 0.0001),
Cushing disease (0.3% vs 0.1%, p < 0.0001), osteoporosis (13.2% vs 9.1%, p <
0.0001), and DM (27.9% vs 20.7%, p < 0.0001) in the PsA group compared with the
control group. In the multivariable regression analysis, the following diseases
were more frequent in the PsA group: hypothyroidism (OR 1.61, 95% CI 1.47-1.81),
DM (OR 1.35, 95% CI 1.18-1.42), Cushing disease (OR 3.96, 95% CI 1.67-9.43), and
osteoporosis (OR 1.56, 95% CI 1.37-1.78). CONCLUSION: PsA is associated with a
high frequency of hypothyroidism, osteoporosis, DM, and Cushing disease.
Awareness of these comorbidities may help physicians provide the optimal medical
care to patients with PsA.
PMID- 28412707
TI - Application of the 2016 EULAR/ACR/PRINTO Classification Criteria for Macrophage
Activation Syndrome in Patients with Adult-onset Still Disease.
AB - OBJECTIVE: To evaluate the clinical significance of the 2016 European League
Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric
Rheumatology International Trials Organization (PRINTO) classification criteria
for macrophage activation syndrome (MAS) in patients with adult-onset Still
disease (AOSD). METHODS: We performed a retrospective analysis of patients with
AOSD with fever who were admitted to Severance Hospital between 2005 and 2016.
The patients with AOSD were evaluated for MAS using the 2016 classification
criteria for MAS. Clinical features, laboratory findings, and overall survival
were analyzed. Logistic regression analysis was used to evaluate the factors
associated with in-hospital mortality. RESULTS: Among 64 patients with AOSD, 36
(56.3%) were classified as having MAS. The overall survival rate was
significantly lower in patients with MAS than in those without (67% vs 100%, p <
0.001). Multivariate analysis showed that a low erythrocyte sedimentation rate, a
low albumin level, an increase in ferritin of over 2 folds, and the development
of MAS on admission were significantly associated with mortality in patients with
AOSD. CONCLUSION: The 2016 EULAR/ACR/PRINTO classification criteria for MAS are
potentially useful for the identification of patients with AOSD at high risk for
a poor outcome. Febrile patients with AOSD should be monitored with the 2016
classification criteria for MAS in the early diagnosis and proper treatment of
MAS.
PMID- 28412708
TI - Validity and Reliability of Patient Reported Outcomes Measurement Information
System Computerized Adaptive Tests in Systemic Lupus Erythematosus.
AB - OBJECTIVE: The aims of this study were to assess the construct validity and the
test-retest reliability of Patient Reported Outcomes Measurement Information
System (PROMIS) computerized adaptive tests (CAT) in patients with systemic lupus
erythematosus (SLE). METHODS: Adults with SLE completed the Medical Outcomes
Study Short Form-36, LupusQoL-US version ("legacy instruments"), and 14 selected
PROMIS CAT. Using Spearman correlations, PROMIS CAT were compared with similar
domains measured with legacy instruments. CAT were also correlated with the
Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus
Erythematosus Disease Activity Index (SELENA-SLEDAI) disease activity and the
Systemic Lupus International Collaborating Clinics/American College of
Rheumatology Damage Index (SDI) scores. Test-retest reliability was evaluated
using ICC. RESULTS: There were 204 outpatients with SLE enrolled in the study and
162 completed a retest. PROMIS CAT showed good performance characteristics and
moderate to strong correlations with similar domains in the 2 legacy instruments
(r = -0.49 to 0.86, p < 0.001). However, correlations between PROMIS CAT and the
SELENA-SLEDAI disease activity and SDI were generally weak and statistically
insignificant. PROMIS CAT test-retest ICC were good to excellent, ranging from
0.72 to 0.88. CONCLUSION: To our knowledge, these data are the first to show that
PROMIS CAT are valid and reliable for many SLE-relevant domains. Importantly,
PROMIS scores did not correlate well with physician-derived measures. This
disconnect between objective signs and symptoms and the subjective patient
disease experience underscores the crucial need to integrate patient-reported
outcomes into clinical care to ensure optimal disease management.
PMID- 28412709
TI - The Association of Low Income with Functional Status and Disease Burden in German
Patients with Rheumatoid Arthritis: Results of a Cross-sectional Questionnaire
Survey Based on Claims Data.
AB - OBJECTIVE: To assess the influence of income on self-reported disease and work
productivity outcomes. METHODS: Persons with rheumatoid arthritis (RA) diagnosis
(International Classification of Diseases, 10th ed. codes M05/M06) on health
insurance claims data in at least 2 quarters of 2013 were randomly selected. They
were mailed questionnaires covering RA diagnosis, household income, functional
capacity [Hannover functional status questionnaire (FFbH), 0-100], RA Impact of
Disease questionnaire (RAID; 0-10), self-reported swollen joint count (SJC; 0
48), tender joint count (TJC; 0-50), and effect of RA on work productivity
(change of work, fewer working hours, sick leave, application for disability
pension, and others). Weighted multivariable linear regression models were used
to assess the association between income and disease outcomes. RESULTS: A total
of 1492 persons of working age who confirmed RA diagnosis were available for
analysis. The mean age was 55 years, 82% were women, and 74% were under
rheumatologic care. A total of 27%, 52%, and 21% had a low (< ?1500), medium
(?1500-3200), and high monthly income (> ?3200), respectively. Respondents with
low income had the worst mean FFbH, RAID, SJC, and TJC values. This was confirmed
in the regression model: mean FFbH low versus high income -8.65 (95% CI -9.72 to
7.58), RAID 0.73 (0.59-0.86), and SJC 3.47 (2.86-4.08). Sick leave
(8.7%/3.5%/1.8%) and disability pension (18.1%/9.6%/6.9%) were more frequent in
patients with low versus medium versus high income (p < 0.05). CONCLUSION: The
association of low income with a higher disease burden, more functional
disability, and higher rates of work loss emphasizes the need to focus on these
outcomes when choosing treatment strategies for patients in the lower income
groups.
PMID- 28412710
TI - Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in
Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic
Literature Review.
AB - OBJECTIVE: For patients with rheumatoid arthritis (RA) who have an inadequate
response to methotrexate (MTX), the relative effectiveness of the combination of
conventional disease-modifying antirheumatic drugs (DMARD) compared with the
combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line
therapy, is uncertain. The aim of this study was to compare the efficacy and
tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX
in patients with RA after MTX failure. METHODS: We performed a systematic search
of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library,
and abstracts from the American College of Rheumatology (ACR) and the European
League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were
included if they were of randomized controlled trials of patients receiving
triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine)
compared with anti-TNF agents plus MTX. Treatment effects were examined by
disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR
response criteria, structural damage by the modified total Sharp score, and
functional disability by the Health Assessment Questionnaire (HAQ). RESULTS: Our
search identified 263 articles; only 5 fulfilled the selection criteria. Analysis
of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti
TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse
events did not differ between treatments. CONCLUSION: In patients with RA in whom
MTX has failed, the addition of a TNF antagonist to MTX may be a valid option,
with better clinical outcomes and better radiographic results in the presence of
poor prognostic factors. In the absence of poor prognostic factors and/or with
contraindications to biologic agents, TT retains its place in the therapeutic
strategy for RA in a currently restricted economic context.
PMID- 28412711
TI - Biologic Disease-modifying Antirheumatic Drug (bDMARD)-induced Neutropenia: A
Registry from a Retrospective Cohort of Patients with Rheumatic Diseases Treated
with 3 Classes of Intravenous bDMARD.
AB - OBJECTIVE: To examine the rate, risks factors, and consequences of neutropenia
induced by intravenous (IV) biologic disease-modifying antirheumatic drugs
(bDMARD). METHODS: We conducted a retrospective cohort study in 499 patients with
rheumatic diseases treated by IV abatacept (ABA), infliximab (IFX), or
tocilizumab (TCZ). RESULTS: Rheumatoid arthritis (RA) was the most frequent
diagnosis (72%). Fifty-two patients (10.4%) experienced at least 1 episode of
neutropenia. No episodes of grade 4 neutropenia were documented. TCZ was more
frequently related to neutropenia than ABA or IFX (18.6% vs 3.8% and 2.8%,
respectively, p < 0.001). The following factors were identified as predictors of
experiencing neutropenia with IV bDMARD: history of neutropenia with methotrexate
(MTX; synthetic DMARD; OR 1.56, 95% CI 1.17-7.14), concomitant treatment by MTX
(OR 1.21, 95% CI 1.01-2.64), and TCZ treatment (OR 2.72, 95% CI 1.53-9.05).
Patients experiencing a TCZ-induced neutropenia did not show a higher risk of
severe infections; however, this group had a shorter drug survival (9 mos vs 20
mos, p < 0.02) compared with TCZ patients without neutropenia. CONCLUSION: Among
3 different classes of IV bDMARD, TCZ is associated with the higher risk of
neutropenia. No increased frequency of infection episodes was documented in this
group.
PMID- 28412712
TI - Antitumor Necrosis Factor-alpha Therapy Associated with Inflammatory Bowel
Disease: Three Cases and a Systematic Literature Review.
AB - OBJECTIVE: Antitumor necrosis factor-alpha (anti-TNF-alpha) therapy is the most
prescribed biologic agent therapy in rheumatology and gastroenterology. However,
a number of serious side effects have been reported with these drugs. Only a
handful of cases of new-onset inflammatory bowel disease (IBD), mostly in
children diagnosed with juvenile idiopathic arthritis (JIA), have been reported
during anti-TNF-alpha therapy. We present 3 cases of adult IBD following anti-TNF
alpha therapy and a literature review on this topic. METHODS: We searched PubMed
MESH for all relevant terms, papers were reviewed, and patient-specific data were
extracted. Relevant clinical data were calculated and presented. RESULTS: The
PubMed search resulted in 137 articles, of which 11 articles and 4 cited
publications were included in our analysis. We found 53 cases of IBD after anti
TNF-alpha therapy reported in the literature; most of them were case series
collected retrospectively from national databases or studies. Almost all the
patients developed IBD after the introduction of etanercept (ETN); 2 patients
with rheumatoid arthritis were also included. The average age at IBD onset was
17.3 years and the average time from ETN introduction to IBD onset was 27 months
(+/- 24). Gastrointestinal symptoms have been reported as improving or subsiding
in most of the patients after discontinuing ETN. CONCLUSION: Although this
manifestation is not common, it should be taken into consideration as an adverse
effect of ETN. Rheumatologists, and in particular rheumatologists treating adult
patients, should be aware of this possible complication. Further investigation
about the pathogenic process underlying this phenomenon is warranted.
PMID- 28412713
TI - Investigation of feet functions of large ruminants with a decoupled model of
equivalent mechanism.
AB - Cloven hooves of ruminants adapt to diverse terrain, provide propulsive force and
support the whole body during movement in natural environments. To reveal how the
feet ensure terrain adaptability by choosing the proper configurations and
terrain conditions, we model the feet of ruminants as an equivalent mechanism
with flexion-extension and lateral movement decoupled. The upper part of the
equivalent mechanism can flex and extend, while the lower part performs the
lateral movement. Combination of the two parts can adapt to longitudinal slope
(anterior-posterior) and transverse slope (medial-lateral), respectively. When
one of two digits closes laterally, the workspace of the other decreases. The
distal interdigital ligament between two digits limits their motion by elastic
force and stores energy during movement. Differences in elastic energy variation
of the ligament on different transverse slopes are characterized based on the
configurations of two digits and the elastic energy between them. If the upper
one of two symmetric digits is fixed, the foot landing on the grade surface (2
degrees ) shows greater capacity for absorbing energy; otherwise, level ground is
the best choice for ruminants. As for the asymmetric digits, longer lateral
digits enhance the optimal adaptive lateral angle. The asymmetry predisposes the
feet to damage on the hard ground, which indicates soft ground is more suitable.
PMID- 28412715
TI - Non-centralized and functionally localized nervous system of ophiuroids: evidence
from topical anesthetic experiments.
AB - Ophiuroids locomote along the seafloor by coordinated rhythmic movements of multi
segmented arms. The mechanisms by which such coordinated movements are achieved
are a focus of interest from the standpoints of neurobiology and robotics,
because ophiuroids appear to lack a central nervous system that could exert
centralized control over five arms. To explore the underlying mechanism of arm
coordination, we examined the effects of selective anesthesia to various parts of
the body of ophiuroids on locomotion. We observed the following: (1) anesthesia
of the circumoral nerve ring completely blocked the initiation of locomotion;
however, initiation of single arm movement, such as occurs during the retrieval
of food, was unaffected, indicating that the inability to initiate locomotion was
not due to the spread of the anesthetic agent. (2) During locomotion, the
midsegments of the arms periodically made contact with the floor to elevate the
disc. In contrast, the distal segments of the arms were pointed aborally and did
not make contact with the floor. (3) When the midsegments of all arms were
anesthetized, arm movements were rendered completely uncoordinated. In contrast,
even when only one arm was left intact, inter-arm coordination was preserved. (4)
Locomotion was unaffected by anesthesia of the distal arms. (5) A radial nerve
block to the proximal region of an arm abolished coordination among the segments
of that arm, rendering it motionless. These findings indicate that the circumoral
nerve ring and radial nerves play different roles in intra- and inter-arm
coordination in ophiuroids.
PMID- 28412714
TI - Reprogramming towards totipotency is greatly facilitated by synergistic effects
of small molecules.
AB - Animal cloning has been achieved in many species by transplanting differentiated
cell nuclei to unfertilized oocytes. However, the low efficiencies of cloning
have remained an unresolved issue. Here we find that the combination of two small
molecules, trichostatin A (TSA) and vitamin C (VC), under culture condition with
bovine serum albumin deionized by ion-exchange resins, dramatically improves the
cloning efficiency in mice and 15% of cloned embryos develop to term by means of
somatic cell nuclear transfer (SCNT). The improvement was not observed by adding
the non-treated, rather than deionized, bovine serum. RNA-seq analyses of SCNT
embryos at the two-cell stage revealed that the treatment with TSA and VC
resulted in the upregulated expression of previously identified reprogramming
resistant genes. Moreover, the expression of early-embryo-specific retroelements
was upregulated by the TSA and VC treatment. The enhanced gene expression was
relevant to the VC-mediated reduction of histone H3 lysine 9 methylation in SCNT
embryos. Our study thus shows a simply applicable method to greatly improve mouse
cloning efficiency, and furthers our understanding of how somatic nuclei acquire
totipotency.
PMID- 28412716
TI - Tanshinone IIA suppresses the progression of atherosclerosis by inhibiting the
apoptosis of vascular smooth muscle cells and the proliferation and migration of
macrophages induced by ox-LDL.
AB - The profound inhibitory effect of Tanshinone IIA (Tan IIA) on atherosclerosis has
been demonstrated, whereas the latent mechanism is not completely cleared. This
study aimed to investigate the cellular and molecular mechanisms underlying Tan
IIA protecting against atherosclerosis. Oil Red O staining and ELISA assay showed
that Tan IIA suppressed the progress of atherosclerosis and reduced the levels of
inflammatory cytokines in serum of apolipoprotein E deficient (ApoE -/- ) mice.
Flow cytometry assay revealed that Tan IIA inhibited oxidized LDL (ox-LDL)
induced apoptosis of VSMCs. MTT and transwell assay indicated that Tan IIA
suppressed the ox-LDL-stimulated proliferation and migration of RAW264.7 cells.
Moreover, Tan IIA ameliorated inflammatory cytokine upregulation elicited by ox
LDL in RAW264.7 cells. Additionally, Tan IIA inhibited the apoptosis of VSMCs and
decreased the levels of MMP-2, MMP-9 in ApoE-/- mice. In conclusion, our study
demonstrated Tan IIA suppressed the progression of atherosclerosis by inhibiting
vascular inflammation, apoptosis of VSMCs and proliferation and migration of
macrophages induced by ox-LDL.
PMID- 28412717
TI - Fibrinogen determination according to Clauss: commutability assessment of
International and commercial standards and quality control samples.
AB - BACKGROUND: Many clinical laboratories use a clotting rate assay according to
Clauss for the determination of fibrinogen in citrated plasma. The aim of the
present study was to assess the commutability of the current International
Standard for fibrinogen (coded 09/264), three commercial fibrinogen standards,
and 10 freeze-dried plasma quality control samples from various sources. METHODS:
Clotting rate assays according to Clauss were performed on three automated
instruments (Sysmex CA1500, STA-Rack Evolution and ACL-Top 700), using three
commercial thrombin reagents (Siemens, Stago, and Instrumentation Laboratory).
Relationships between the results obtained with the three instruments were
determined with 25 fresh-frozen plasma samples obtained from patients. The
deviations of the assay results obtained with the freeze-dried samples were
compared with the deviations obtained with the fresh-frozen samples, according to
approved CLSI guideline C53A. RESULTS: Freezing and thawing had no influence on
the assay results. There were significant differences in the mean assay results
(fibrinogen, g/L) for the fresh-frozen plasma samples between the three automated
instruments: 2.51 (STA-Rack Evolution), 2.25 (ACL-Top 700) and 2.20 (Sysmex
CA1500). Similar differences were observed for several freeze-dried plasma
samples. Some freeze-dried plasma samples, including the International Standard,
were out of the 95% confidence interval for the relationship between STA-Rack
Evolution and Sysmex CA1500. CONCLUSIONS: Some freeze-dried plasmas including the
international standard for fibrinogen are not commutable among automated
instruments for fibrinogen clotting rate assays according to Clauss. Our results
have consequences for all interested parties in the traceability chain (WHO,
industry, external quality assessment schemes, clinical laboratories).
PMID- 28412718
TI - Prognostic value of total antioxidant capacity to predict functional outcome in
traumatic brain injury patients.
PMID- 28412719
TI - Combined measurement of factor XIII and D-dimer is helpful for differential
diagnosis in patients with suspected pulmonary embolism.
AB - BACKGROUND: D-dimer has been used to rule out pulmonary embolism (PE). Based on
previous reports of decreased concentrations of coagulation factor XIII (FXIII)
in venous thromboembolism, and no change in FXIII concentration in patients with
acute cardiovascular disease, we evaluated the benefit of simultaneously
measuring D-dimer and FXIII concentrations for diagnosing PE. METHODS: In this
prospective single-center study, we enrolled 209 patients initially suspected of
having PE, and measured their D-dimer and FXIII concentrations. Forty-one
patients were diagnosed with PE and 168 with other final diagnoses, including
acute coronary syndrome (ACS); aortic dissection (AD); spontaneous pneumothorax
(SP); other respiratory, heart, digestive and nervous diseases; and uncertain
diagnoses. RESULTS: Patients with PE had significantly higher D-dimer and lower
FXIII concentrations than did patients without PE. Combined D-dimer and FXIII
measurements provided a higher positive predictive value (76.6%) for PE than
single tests, especially in patients with Wells score >4.0 (89.3%). Specifically,
patients with AD or ACS showed higher FXIII concentrations and mean platelet
volumes than did patients with PE or SP, and patients with PE and AD had higher D
dimer concentrations than did other patients. At the thresholds of 69.0% for
FXIII and 1.10 MUg/mL for D-dimer, 123/151 patients (81.5%) with serious diseases
(PE, AD, ACS and SP) were correctly distinguished. CONCLUSIONS: Combined
measurement of D-dimer and FXIII helps distinguish PE from serious diseases with
similar symptoms and appears to relate to increased FXIII release from active
platelets in cardiovascular disease.
PMID- 28412720
TI - Mean hemoglobin concentrations in fasting venous and non-fasting capillary blood
of Cambodian women using a hemoglobinometer and an automated hematology analyzer.
PMID- 28412722
TI - Integrating traditional Chinese medicine into Chinese medical education reform:
issues and challenges.
PMID- 28412721
TI - Are admission procalcitonin levels universal mortality predictors across
different medical emergency patient populations? Results from the multi-national,
prospective, observational TRIAGE study.
AB - BACKGROUND: Procalcitonin (PCT), an inflammatory blood biomarker, is well studied
in infectious diseases. Its prognostic value in unselected emergency department
(ED) patients remains yet undefined. Herein, we investigated association of
admission PCT levels and mortality in a large, international-multicenter ED
patient cohort. METHODS: We prospectively enrolled 6970 unselected, consecutive,
adult, medical patients seeking ED care in three tertiary-care hospitals in
Switzerland, France and the USA. We used multivariable logistic regression models
to examine association of admission PCT levels (as a continuous predictor and
across cut-offs) and 30-day mortality. We also investigated subgroup effects by
main diagnosis, comorbidities and clinical features at presentation. RESULTS:
During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased
stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%,
13% to 15%, respectively. This association was also confirmed in a fully-adjusted
model including age, gender, main symptom, main diagnosis and vital parameters on
admission. Receiver operating characteristic (ROC) curve analysis showed that PCT
differentiated well between survivors and non-survivors in the overall cohort
(area under ROC curve [AUC] 0.75) with best results for patient with metabolic
(AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved
the prognostic accuracy of the quick sequential organ failure assessment (qSOFA)
score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other
secondary endpoints including intensive care unit (ICU) admission and hospital
readmission. CONCLUSIONS: In this large and heterogenous medical ED patient
cohort, admission PCT was a strong and independent outcome predictor for 30-day
mortality across different medical diagnoses independent of underlying infection.
PCT may help to improve risk stratification in unselected medical ED patients.
PMID- 28412723
TI - Can video game dynamics identify orthopaedic surgery residents who will succeed
in training?
PMID- 28412724
TI - The quality of the educational environment in a medical college in Saudi Arabia.
AB - Objectives: The study aimed to examine the quality of the educational environment
in the Faculty of Medicine, University of Tabuk, Saudi Arabia, and to compare
between male and female students using the Dundee Ready Educational Environment
Measure (DREEM). Methods: We utilized a cross-sectional survey design.
Participants were 221 medical students (96 males and 125 females) from all
classes (1st to 6th year). Each participant responded to a translated version of
the DREEM questionnaire that measures five domains: students' perception of
learning (SPL), students' perception of teachers (SPT), students' academic self
perception (SASP), students' perception of atmosphere (SPA), and students' social
self-perception (SSSP). Numerical differences between male and female students
were analyzed using the Student's t-test. Results: The global average score of
female students was significantly higher (105.0+/-22.9, 53% of maximum score)
than male students (98.3+/-24.3, 49% of maximum score; t(219)= -2.119, p= 0.035).
The major gender difference was found in the SPT domain, with a higher score in
the females (60%) compared to the male (50%) cohort (t (219)= -5.519, p = 0.000).
Differences in the other domains were statistically insignificant. Out of the 50
DREEM items, the items that need attention were 32 and 23 on the male and the
female sides respectively. Conclusions: The perception of the educational
environment by the female students is significantly better than male students.
The study provides valuable information about many educational problems that need
attention. DREEM-based surveys are highly recommended for periodic monitoring of
the educational environment.
PMID- 28412725
TI - Immunohistochemical Ki67 after short-term hormone therapy identifies low-risk
breast cancers as reliably as genomic markers.
AB - BACKGROUND: The purpose of this study was to test whether immunohistochemical
(IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67)
predict similar numbers of patients with favorable prognoses as genomic markers.
RESULTS: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67
levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post
Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate
signature(GSS) (66.7%: 20/30), but the difference in predictive power was not
significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2)
and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly
downregulated after therapy (P < 0.001 and 0.041, respectively). MATERIALS AND
METHODS: Core needle biopsy specimens of primary breast cancer were collected at
Okayama University Hospital from hormone receptor-positive and human epidermal
growth factor 2-negative patients that subsequently received two weeks of
neoadjuvant hormone therapy. Paired post-treatment specimens from surgical
samples were also collected. IHC Ki67 levels and GSS were compared between pre-
and post-hormone treatment samples. Changes of gene expression pattern in short
term hormone therapy were also assessed. CONCLUSIONS: IHC based post-Ki67 levels
may have distinct predictive power compared with the naive IHC Ki67. Future
studies with larger cohorts and longer follow-up periods may be needed to
validate our results.
PMID- 28412726
TI - Inhaled corticosteroids have a protective effect against lung cancer in female
patients with chronic obstructive pulmonary disease: a nationwide population
based cohort study.
AB - Whether the use of inhaled corticosteroids (ICS) protects patients with chronic
obstructive pulmonary disease (COPD) from lung cancer remains undetermined. In
this retrospective nationwide population-based cohort study, we extracted data of
13,686 female COPD patients (ICS users, n = 1,290, ICS non-users, n = 12,396)
diagnosed between 1997 and 2009 from the Taiwan's National Health Insurance
database. These patients were followed-up until 2011, and lung cancer incidence
was determined. Cox regression analysis was used to estimate hazard ratios (HRs)
for lung cancer incidence. The time to lung cancer diagnosis was significantly
different between ICS users and non-users (10.75 vs. 9.68 years, P < 0.001). Per
100,000 person-years, the lung cancer incidence rate was 235.92 for non-users and
158.67 for users [HR = 0.70 (95% confidence interval {CI}: 0.46-1.09)]. After
adjusting for patients' age, income, and comorbidities, a cumulative ICS dose >
39.48 mg was significantly associated with a lower risk of lung cancer [ICS users
> 39.48 mg, HR = 0.45 (95% CI: 0.21-0.96)]. Age >= 60 years, pneumonia, diabetes
mellitus, and hypertension decreased lung cancer risk, whereas pulmonary
tuberculosis increased the risk. Our results suggest that ICS have a potential
role in lung cancer prevention among female COPD patients.
PMID- 28412727
TI - ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid
leukemia.
AB - Zinc finger protein 521 (ZNF521) is a multiple zinc finger transcription factor
and a strong candidate as regulator of hematopoietic stem cell homeostasis.
Recently, independent gene expression profile studies have evidenced a positive
correlation between ZNF521 mRNA overexpression and MLL-rearranged acute myeloid
leukemia (AML), leaving open the question on the role of ZNF521 in this subtype
of leukemia. In this study, we sought to analyze the effect of ZNF521 depletion
on MLL-rearranged AML cell lines and MLL-AF9 xenograft primary cells. Knockdown
of ZNF521 with short-hairpin RNA (shRNA) led to decreased leukemia proliferation,
reduced colony formation and caused cell cycle arrest in MLL-rearranged AML cell
lines. Importantly, we showed that loss of ZNF521 substantially caused
differentiation of both MLL-rearranged cell lines and primary cells. Moreover,
gene profile analysis in ZNF521-silenced THP-1 cells revealed a loss of MLL-AF9
directed leukemic signature and an increase of the differentiation program.
Finally, we determined that both MLL-AF9 and MLL-ENL fusion proteins directly
interacted with ZNF521 promoter activating its transcription. In conclusion, our
findings identify ZNF521 as a critical effector of MLL fusion proteins in
blocking myeloid differentiation and highlight ZNF521 as a potential therapeutic
target for this subtype of leukemia.
PMID- 28412728
TI - Increased reactive oxygen species levels cause ER stress and cytotoxicity in
andrographolide treated colon cancer cells.
AB - Chemotherapy continues to play an essential role in the management of many
cancers including colon cancer, the third leading cause of death due to cancer in
the United States. Many naturally occurring plant compounds have been
demonstrated to possess anti-cancer cell activity and have the potential to
supplement existing chemotherapy strategies. The plant metabolite andrographolide
induces cell death in cancer cells and apoptosis is dependent upon the induction
of endoplasmic reticulum stress (ER stress) leading to the unfolded protein
response (UPR). The goal of the present study was to determine the mechanism by
which andrographolide induces ER stress and to further evaluate its role in
promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used
to demonstrate that andrographolide induces increased ROS levels, corresponding
anti-oxidant response molecules, and reduced mitochondrial membrane potential. No
increases in ROS levels were detected in control colon fibroblast cells.
Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3
apoptosis elements were all inhibited in the presence of the ROS scavenger NAC.
Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also
reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR
levels that are normally suppressed by andrographolide were also expressed at
normal levels in the absence of ROS. These data demonstrate that andrographolide
induces ER stress leading to apoptosis through the induction of ROS and that
elevated ROS also play an important role in down-regulating cell cycle
progression and cell survival pathways as well.
PMID- 28412729
TI - STK31 as novel biomarker of metastatic potential and tumorigenicity of colorectal
cancer.
AB - PURPOSE: Colorectal cancer (CRC) is the fifth most common cause of cancer deaths
in China and fourth worldwide. Metastatic dissemination of primary tumors is
considered main cause for CRC related mortality. The serine-threonine kinase 31
(STK31) gene is a novel cancer testis (CT) antigen. It was found significantly
highly expressed in gastrointestinal cancers. In our study we aimed to analyze
the correlation between STK31 expression patterns and metastasization, tumor
stage and grade in CRC patients. RESULTS: Relative STK31 expression level was
significantly higher in patients with lymph node metastasis. STK31 expression
levels in primary tumorous tissues of metastatic patients were significantly
higher than in ANCTs and in lymph nodes samples, both at the RNA level and the
protein level. MATERIALS AND METHODS: Surgical specimens of cancerous tissues,
paired with adjacent noncancerous tissues, and lymph nodes from 44 CRC cases with
different clinicopathological features were collected. Expression of STK31 was
detected and measured by immunohistochemistry and quantitative real-time
polymerase chain reaction (QRT-PCR). CONCLUSIONS: Our data suggest that STK31
might be a potential biomarker in detecting, monitoring and predicting the
metastatic risk of colorectal cancer.
PMID- 28412730
TI - The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor
response to chemotherapy in chronic lymphocytic leukemia.
AB - The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer
research, in part due to their ability to serve as disease biomarkers. However,
few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We
have identified one particular lncRNA, treRNA, which is overexpressed in CLL B
cells. We measured transcript expression in 144 CLL patient samples and separated
samples into high or low expression of treRNA relative to the overall median. We
found that high expression of treRNA is significantly associated with shorter
time to treatment. High treRNA also correlates with poor prognostic indicators
such as unmutated IGHV and high ZAP70 protein expression. We validated these
initial findings in samples collected in a clinical trial comparing the
nucleoside analog fludarabine alone or in combination with the alkylating agent
cyclophosphamide in untreated CLL samples collected prior to starting therapy
(E2997). High expression of treRNA was independently prognostic for shorter
progression free survival in patients receiving fludarabine plus
cyclophosphamide. Given these results, in order to study the role of treRNA in
DNA damage response we generated a model cell line system where treRNA was over
expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control
line, there was less cell death in OSU-CLL over-expressing treRNA after exposure
to fludarabine and mafosfamide, due in part to a reduction in DNA damage.
Therefore, we suggest that treRNA is a novel biomarker in CLL associated with
aggressive disease and poor response to chemotherapy through enhanced protection
against cytotoxic mediated DNA damage.
PMID- 28412731
TI - C-terminal binding protein-2 promotes cell proliferation and migration in breast
cancer via suppression of p16INK4A.
AB - C-terminal binding protein-2 (CtBP2) enhances cancer proliferation and
metastasis. The role and mechanism of CtBP2 in breast cancer remains to be
elucidated. Western blot and immunochemistry were employed to evaluate the level
of CtBP2 and p16INK4A in breast cancer. Genetic manipulation was used to study
the expression of p16INK4A and its downstream genes regulated by CtBP2.
Functional assays, including colony formation, wound healing, transwell invasion,
anchorage-independent growth assay and a xenograft tumor model were used to
determine the oncogenic role of CtBP2 in breast cancer progression. The
expression of CtBP2 was increased in breast cancer tissues and cell lines. The
expression of p16INK4A were inversely correlated CtBP2 (r2 = 0.43, P < 0.01). The
expression of both CtBP2 and p16INK4A were significantly related to histological
differentiation (P < 0.01 and P = 0.004, respectively) and metastasis (P = 0.046
and 0.047, respectively). The overall survival rate was lower in patients with
increased CtBP2 expression and lower p16INK4A expression. Knockdown of CtBP2
resulted in the activation of p16INK4A and down-regulation of cell cycle
regulators cyclin D, cyclin E and cyclin-dependent kinase 2 and 4. This down
regulation also led to a decreased transition of the G1-S phase in breast cancer
cells. Moreover, gain-of-function experiments showed that CtBP2 suppressed
p16INK4A and matrix metalloproteinase-2, subsequently enhancing the migration in
breast cancer. However, the silence of CtBP2 abrogated this effect. Collectively,
these findings provide insight into the role CtBP2 plays in promoting
proliferation and migration in breast cancer by the inhibition of p16INK4A.
PMID- 28412733
TI - Prevention of tumor seeding during needle biopsy by chemotherapeutic-releasing
gelatin sticks.
AB - Needle biopsy is an indispensable diagnostic tool in obtaining tumor tissue for
diagnostic examination. Tumor cell seeding in the needle track during
percutaneous needle biopsies has been reported for various types of cancers. The
mechanical force of the biopsy both directly displaces the malignant cells and
causes bleeding and fluid movement that can further disseminate cells. To prevent
the risk of tumor cell seeding during biopsy, we developed a gelatin stick loaded
with chemotherapeutics such as doxorubicin (DXR) that was inserted into the
biopsy canal. The gelatin-doxorubicin sticks (GDSs) were created by passively
loading precut gelatin foam strips (Gelfoam) with doxorubicin solution. The dried
GDSs were inserted into the needle track through the sheath during the needle
biopsy and eventually self-absorbed. We showed that this procedure prevented
iatrogenic tumor seeding during needle biopsies in two subcutaneous tumor models.
In an alternative application, using GDSs in intracranial brain tumor
implantation avoided the outgrowth of tumor from the rodent brain, which could
otherwise potentially fuse the tumor with the meninges and distort the results in
therapeutic studies in rodent brain tumor models.
PMID- 28412732
TI - Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as
potential therapeutic agent for gallbladder cancer.
AB - Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with
high invasiveness and poor response to chemotherapy and radiotherapy. New
therapeutic approaches are urgently needed in order to improve survival and
response rates of GBC patients. We screened 130 small molecule inhibitors on a
panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of
the most potent inhibitory drugs across the different lines. We tested the
antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous
preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90
by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG
and GA significantly reduced the expression of HSP90 target proteins, including
EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular
changes were consistent with reduced cell viability and cell migration and
promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro
studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size,
exhibiting a 69.6% reduction in tumor size in the treatment group compared to
control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in
182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%),
moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical
observations strongly suggest that the inhibition of HSP90 function by HSP90
inhibitors is a promising therapeutic strategy for gallbladder cancer that may
benefit from new HSP90 inhibitors currently in development.
PMID- 28412734
TI - Whole genome sequencing of matched tumor, adjacent non-tumor tissues and
corresponding normal blood samples of hepatocellular carcinoma patients revealed
dynamic changes of the mutations profiles during hepatocarcinogenesis.
AB - Hepatocellular carcinoma (HCC) has become the third most deadly disease worldwide
and HBV is the major factor in Asia and Africa. We conducted 9 WGS (whole genome
sequencing) analyses for matched samples of tumor, adjacent non-tumor tissues and
normal blood samples of HCC patients from three HBV positive patients. We then
validated the mutations identified in a larger cohort of 177 HCC patients. We
found that the number of the unique somatic mutations (average of 59,136) in
tumor samples is significantly less than that in adjacent non-tumor tissues
(average 83, 633). We discovered that the TP53 R249S mutation occurred in 7.7% of
the HCC patients, and it was significantly associated with poor diagnosis. In
addition, we found that the L104P mutation in the VCX gene (Variable charge, X
linked) was absent in white blood cell samples, but present at 11.1% frequency in
the adjacent tissues and increased to 14.6% in HCC tissues, suggesting that this
mutation might be a tumor driver gene driving HCC carcinogenesis. Finally, we
identified a TK1-RNU7 fusion, which would result in a deletion of 103 amino acids
from its C-terminal. The frequencies of this fusion event decreased from the
adjacent tissues (29.2%) to the tumors (16.7%), suggesting that a truncated
thymidine Kinase1 (TK1) caused by the fusion event might be deleterious and be
selected against during tumor progression. The three-way comparisons allow the
identification of potential driver mutations of carcinogenesis. Furthermore, our
dataset provides the research community a valuable dataset for identifying
dynamic changes of mutation profiles and driver mutations for HCC.
PMID- 28412735
TI - Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of
NNMT.
AB - Glucose is considered the primary energy source for all cells, and some cancers
are addicted to glucose. Here, we investigated the functional consequences of
chronic glucose deprivation in serous ovarian cancer cells. We found that cells
resistant to glucose starvation (glucose-restricted cells) demonstrated increased
metabolic plasticity that was dependent on NNMT (Nicotinamide N
methyltransferase) expression. We further show that ZEB1 induced NNMT, rendered
cells resistant to glucose deprivation and recapitulated metabolic adaptations
and mesenchymal gene expression observed in glucose-restricted cells. NNMT
depletion reversed metabolic plasticity in glucose-restricted cells and prevented
de novo formation of glucose-restricted colonies. In addition to its role in
glucose independence, we found that NNMT was required for other ZEB1-induced
phenotypes, such as increased migration. NNMT protein levels were also elevated
in metastatic and recurrent tumors compared to matched primary carcinomas, while
normal ovary and fallopian tube tissue had no detectable NNMT expression. Our
studies define a novel ZEB1/NNMT signaling axis, which elicits mesenchymal gene
expression, as well as phenotypic and metabolic plasticity in ovarian cancer
cells upon chronic glucose starvation. Understanding the causes of cancer cell
plasticity is crucial for the development of therapeutic strategies to counter
intratumoral heterogeneity, acquired drug resistance and recurrence in high-grade
serous ovarian cancer (HGSC).
PMID- 28412736
TI - Tumor biology, clinicopathological characteristics and prognosis of screen
detected T1 invasive non-palpable breast cancer in asymptomatic Chinese women
(2001-2014).
AB - BACKGROUND: Mammography screening usually detects low-risk breast cancer in the
western world. However, little is known about the ultrasound and mammography
screen-detected T1 invasive non-palpable breast cancer (NPBC) in asymptomatic
Chinese women. RESULTS: With the increase of tumor size (T1a, b, c), lymph node
positivity (8.7%, 18.3%, 26.0%, p = 0.018), pN (p = 0.028) and TNM stage (p =
0.035) increased accordingly. Tumor size (T1a, b, c) was correlated with high Ki
67 index (defined as >= 14%, 37.9%, 45.8%, 56.2%, p = 0.017), chemotherapy
(20.4%, 35.2%, 57.3%, p < 0.001) and targeted therapy (2.9%, 9.9%, 15.1%, p =
0.008). T1a disease had higher chance of being luminal A and accompanied with
ductal carcinoma in situ (DCIS), while T1c tumor being triple-negative and
without DCIS. The 5-year disease free survival (DFS) of T1a, b, c NPBC were
99.0%, 96.9% and 92.9%, whereas the 5-year overall survival (OS) were 100.0%,
100.0% and 97.9% respectively. There was no significant difference in 5-year DFS
or OS among the T1 NPBC subgroups or subtypes/immunophenotypes. PATIENTS AND
METHODS: From 2001 to 2014, 4,574 screening positive women received biopsies in
Peking Union Medical College (PUMC) Hospital, and 729 NPBC including 437 T1
unilateral invasive NPBC were diagnosed. With a median follow-up time of 32
months (6-163 months), the clinicopathological characteristics, treatment choice,
5-year DFS and OS were compared between T1a, T1b and T1c NPBC. The DFS and OS
prognostic factors were identified. CONCLUSION: Screen-detected T1 invasive NPBC
could be regarded as low-risk cancer in Chinese women. TNM stage and LN
metastasis instead of molecular subtype was identified as the DFS prognostic
factors while radiotherapy as the OS predictor.
PMID- 28412737
TI - Whole-exome sequencing identifies SGCD and ACVRL1 mutations associated with total
anomalous pulmonary venous return (TAPVR) in Chinese population.
AB - As a rare type of Congenital Heart Defects (CHD), the genetic mechanism of Total
Anomalous Pulmonary Venous Return (TAPVR) remains unknown, although previous
studies have revealed potential disease-driving regions/genes. Blood samples
collected from the 6 sporadic TAPVR cases and 81 non-TAPVR controls were
subjected to whole exome sequencing. All detected variations were confirmed by
direct Sanger sequencing. Here, we identified 2 non-synonymous missense
mutations: c.C652T, p.R218W in activin A receptor type II-like 1 (ACVRL1),
c.C717G, p.D239E in sarcoglycan delta (SGCD). Our results offered the landscape
of mutations for TAPVR in Chinese population firstly and are valuable in the
mutation-based pre- and post-natal screening and genetic diagnosis for TAPVR.
PMID- 28412738
TI - Reduced NOV expression correlates with disease progression in colorectal cancer
and is associated with survival, invasion and chemoresistance of cancer cells.
AB - Aberrant expression of nephroblastoma overexpressed (NOV) has been evident in
certain malignancies. In the current study, we aim to investigate the role played
by NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of
359 CRC tissues and 174 normal colorectal tissues. Its impact on CRC cells was
investigated using in vitro NOV knockdown and overexpression models. NOV
transcripts were reduced in the CRC tumours compared with the paired adjacent
normal colorectal tissues (p < 0.01) and was associated with distant metastases.
NOV knockdown resulted in increased cell proliferation and invasion of RKO cells,
whilst an opposite effect was seen in the HT115 NOV over expressing cells. A
positive association between Caspase-3/-8 and NOV was seen in NOV knockdown and
overexpression cell lines which contributed to the survival of serum deprived CRC
cells. Further investigation showed that NOV regulated proliferation, survival
and invasion through the JNK pathway. NOV knockdown in RKO cells reduced the
responsiveness to 5-Fluorouracil treatment, whilst overexpression in HT115 cells
exhibited a contrasting effect. Taken together, NOV is reduced in CRC tumours and
this is associated with disease progression. NOV inhibits the proliferation and
invasion of CRC cells in vitro. Inhibition of proliferation is mediated by a
regulation of Caspase-3/-8, via the JNK pathway, which has potential for
predicting and preventing chemoresistance.
PMID- 28412739
TI - Retinoic acid receptor alpha drives cell cycle progression and is associated with
increased sensitivity to retinoids in T-cell lymphoma.
AB - Peripheral T-cell lymphomas (PTCLs) are aggressive non-Hodgkin lymphomas with
generally poor outcomes following standard therapy. Few candidate therapeutic
targets have been identified to date. Retinoic acid receptor alpha (RARA) is a
transcription factor that modulates cell growth and differentiation in response
to retinoids. While retinoids have been used to treat some cutaneous T-cell
lymphomas (CTCLs), their mechanism of action and the role of RARA in CTCL and
other mature T-cell lymphomas remain poorly understood. After identifying a PTCL
with a RARAR394Q mutation, we sought to characterize the role of RARA in T-cell
lymphoma cells. Overexpressing wild-type RARA or RARAR394Q significantly
increased cell growth in RARAlow cell lines, while RARA knockdown induced G1
arrest and decreased expression of cyclin-dependent kinases CDK2/4/6 in RARAhigh
cells. The retinoids, AM80 (tamibarotene) and all-trans retinoic acid, caused
dose-dependent growth inhibition, G1 arrest, and CDK2/4/6 down-regulation. Genes
down-regulated in transcriptome data were enriched for cell cycle and G1-S
transition. Finally, RARA overexpression augmented chemosensitivity to retinoids.
In conclusion, RARA drives cyclin-dependent kinase expression, G1-S transition,
and cell growth in T-cell lymphoma. Synthetic retinoids inhibit these functions
in a dose-dependent fashion and are most effective in cells with high RARA
expression, indicating RARA may represent a therapeutic target in some PTCLs.
PMID- 28412740
TI - Combination epidermal growth factor receptor variant III peptide-pulsed dendritic
cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells.
AB - The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is
present in approximately one-third of glioblastoma (GBM) patients. It is never
found in normal tissues; therefore, it represents a candidate target for GBM
immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to
represent a target of glioma and is presented by MHC I/II complexes. Dendritic
cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to
precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by
DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to
precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and
inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression
of TGF-beta1 in the tumour environment, resulting in improved efficacy of T cell
activation and killing via suppressing the SMO/Gli2 axis, which at least
partially reversed the immunosuppressive environment. Furthermore, combining the
EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells
compared with the administration of either one alone. This finding suggested that
a DC-based vaccine combined with miR-326 may induce more powerful anti-tumour
immunity against GBM cells that express a relevant antigen, which provides a
promising approach for GBM immunotherapy.
PMID- 28412741
TI - Opposite effects of GCN5 and PCAF knockdowns on the alternative mechanism of
telomere maintenance.
AB - Cancer cells can use a telomerase-independent mechanism, known as alternative
lengthening of telomeres (ALT), to elongate their telomeres. General control non
derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous
acetyltransferases that are mutually exclusive subunits in SAGA-like complexes.
Here, we reveal that down regulation of GCN5 and PCAF had differential effects on
some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is
present at telomeres and opposes telomere recombination, in contrast to PCAF that
may indirectly favour them in ALT cells.
PMID- 28412742
TI - Association of the long non-coding RNA MALAT1 with the polycomb repressive
complex pathway in T and NK cell lymphoma.
AB - Recently, various long non-coding RNAs (lncRNAs) have been reported to have
significant therapeutic or prognostic value. However, the expression of lncRNAs
has not been investigated in T and NK cell lymphoma. Thus, we evaluated the
biological and prognostic role of lncRNAs related to the polycomb repressive
complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell
lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical
samples and cell lines. High expression of MALAT1 as well as BMI1 was related to
poor prognosis in patients with mature T cell lymphoma. In the tissue samples,
BMI1 expression showed a positive correlation with EZH2, SUZ12, H3K27me3, and
MALAT1. Multiple linear regression analysis showed that BMI1 expression was
independently associated with H3K27me3. Direct binding of MALAT1 to the PRC2
components (EZH2 and SUZ12) was observed in a T cell lymphoma cell line; however,
no direct binding of MALAT1 with H3K27me3 and BMI1 (a PRC1 component) was
observed.In T and NK cell lymphomas, MALAT1 was related to poor prognosis. MALAT1
directly binds to EZH2 and SUZ12, and BMI1 activation may be induced possibly
through H3K27me3.
PMID- 28412743
TI - Autologous transplantation of cytokine-induced killer cells as an adjuvant
therapy for hepatocellular carcinoma in Asia: an update meta-analysis and
systematic review.
AB - BACKGROUND: High recurrence rate after curative treatment is the major problem
for hepatocellular carcinoma (HCC). Cytokine-induced killer cells (CIKs) therapy
was extensively studied among HCC patients. However, the value of CIKs therapy
was controversial. A meta-analysis was performed to investigate the efficacy of
adjuvant CIKs after invasive treatments among HCC patients. METHODS: We searched
online for literatures studying sequential CIKs therapy for HCC patients.
Recurrence-free survival (RFS), progress-free survival (PFS) and overall survival
(OS) were set as the main endpoints. Both overall and subgroup analysis were
accomplished. RESULTS: A total of 12 clinical trials with 1,387 patients were
included. The pooled analysis showed a significant improvement of RFS, PFS and OS
in CIK group (HR 0.56, 95% CI 0.47-0.67, p<0.00001 for RFS; HR 0.53, 95% CI 0.40
0.69, p<0.00001 for PFS; HR 0.59, 95% CI 0.46-0.77, p<0.0001 for OS). The
proportion of CD4+ T cells increased significantly, while CD8+ T cells decreased
significantly after CIKs therapy (WMD 4.07, 95% CI 2.58-5.56, p<0.00001; WMD
2.84, 95% CI -4.67 to -1.01, p=0.002, respectively). No significant differences
of adverse events between CIK and non-CIK group existed. CONCLUSIONS:
Conventionally invasive therapies combined with CIKs therapy could improve the
prognosis of HCC patients, especially for RFS and PFS, with mild side effects.
Optimizing patient selection shall be the direction in future studies.
PMID- 28412744
TI - Mitochondrial VDAC1-based peptides: Attacking oncogenic properties in
glioblastoma.
AB - Glioblastoma multiforme (GBM), a primary brain malignancy characterized by high
morbidity, invasiveness, proliferation, relapse and mortality, is resistant to
chemo- and radiotherapies and lacks effective treatment. GBM tumors undergo
metabolic reprograming and develop anti-apoptotic defenses. We targeted GBM with
a peptide derived from the mitochondrial protein voltage-dependent anion channel
1 (VDAC1), a key component of cell energy, metabolism and apoptosis regulation.
VDAC1-based cell-penetrating peptides perturbed cell energy and metabolic
homeostasis and induced apoptosis in several GBM and GBM-derived stem cell lines.
We found that the peptides simultaneously attacked several oncogenic properties
of human U-87MG cells introduced into sub-cutaneous xenograft mouse model,
inhibiting tumor growth, invasion, and cellular metabolism, stemness and inducing
apoptosis. Peptide-treated tumors showed decreased expression of all tested
metabolism-related enzymes and transporters, and elevated levels of apoptotic
proteins, such as p53, cytochrome c and caspases. Retro-Tf-D-LP4, containing the
human transferrin receptor (TfR)-recognition sequence, crossed the blood-brain
barrier (BBB) via the TfR that is highly expressed in the BBB to strongly inhibit
tumor growth in an intracranial xenograft mouse model. In summary, the VDAC1
based peptides tested here offer a potentially affordable and innovative new
conceptual therapeutic paradigm that might overcome GBM stemness and invasiveness
and reduce relapse rates.
PMID- 28412745
TI - Neutrophil count is associated with myeloid derived suppressor cell level and
presents prognostic value of for hepatocellular carcinoma patients.
AB - Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for
multiple cancers. However, target agents on MDSC have not display promising
efficacy. One of the critical reasons shall be less optimal patient selection. In
the present study, we aimed to identify clinical parameters relevant to MDSC
level in hepatocellular carcinoma (HCC) patients for future MDSC targeted
therapy. In the present study, a series of 55 HCC patients (testing group) and 20
healthy donors were analyzed investigating frequencies of MDSC in peripheral
blood mononuclear cells (PBMC). As a result, we found that MDSC level was
increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p <
0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p <
0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was
positively associated with MDSC level. Then, the prognostic value of the above
predictors was determined in a retrospective database of 255 HCC patients
(validation group). The baseline characteristics of testing and validation group
were similar. Multivariate analysis by Cox regression revealed that neutrophil
count was an independent predictor for overall survival (OS) (p = 0.000, HR
1.065, 95% CI 1.028-1.103), with the rest parameters failed to reach a
significant result. In summary, the present study firstly identified blood
neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And,
patients with higher neutrophil count level might be the optimal patient subgroup
for MDSC targeted therapy.
PMID- 28412746
TI - Kruppel-like factor 4 (KLF4) regulates the miR-183~96~182 cluster under
physiologic and pathologic conditions.
AB - MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post
transcriptionally control the translation and stability of target mRNAs in a
sequence-dependent manner. MiRNAs are essential for key cellular processes
including proliferation, differentiation, cell death and metabolism, among
others. Consequently, alterations of miRNA expression contribute to developmental
defects and a myriad of diseases.The expression of miRNAs can be altered by
several mechanisms including gene copy number alterations, aberrant DNA
methylation, defects of the miRNA processing machinery or unscheduled expression
of transcription factors. In this work, we sought to analyze the regulation of
the miR-182 cluster, located at the 7q32 locus, which encodes three different
miRNAs that are abundantly expressed in human embryonic stem cells and de
regulated in cancer. We have found that the Kruppel-like factor 4 (KLF4) directly
regulates miR-182 cluster expression in human embryonic stem cells (hESCs) and in
melanoma tumors, in which the miR-182 cluster is highly expressed and has a pro
metastatic role. Furthermore, higher KLF4 expression was found to be associated
with metastatic progression and poor patient outcome. Loss of function
experiments revealed that KLF4 is required for melanoma cell maintenance. These
findings provide new insights into the regulation of the miR-182 cluster
expression and new opportunities for therapeutic intervention in tumors in which
the KLF4-miR-182 cluster axis is deregulated.
PMID- 28412747
TI - Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in
selenium-replete men.
AB - According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast
supplement containing selenium, 200 mcg/day, decreased the incidence of total
cancer, cancers of the prostate, colon and lung, and cancer mortality. The active
agent in the selenized yeast supplement was assumed to be selenomethionine
(SEMET), although the supplement had not been well speciated. The SELECT study,
largely motivated by the NPC trial, enrolling nearly 40 times as many subjects,
showed unequivocally that selenium 200 mcg/day, with selenium in the form of
SEMET, does not protect selenium-replete men against prostate or other major
cancer. The agent tested by SELECT, pure SEMET, could have been different from
the selenized yeast tested in NPC. One of the selenium forms suspected of having
chemopreventive effects, and which may have been present in the NPC agent, is
methyl selenocysteine (MSC). This study, with 29 selenium-replete patients
enrolled in a randomized, double-blind trial, compared the multiple-dose
toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were
on trial for 84 days. No toxicity was observed. Although SEMET supplementation
increased blood selenium concentration more than MSC did, neither form had a more
than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and
glutathione peroxidase(GPX).
PMID- 28412748
TI - Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the
switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal
cancer.
AB - Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor
microenvironment and could promote tumor progression. CAFs are usually derived
from resident fibroblasts, which undergoing an activated process stimulated by
tumor cells. However, the agents and mechanism driving this switch have not yet
been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein,
could promote proliferation and angiogenesis of colorectal cancer (CRC) cells,
and high expression of PGRN correlated with patient poor prognosis. Whether PGRN
has effects on the function of stromal fibroblasts is unknown. Herein we found
that there was a positive correlation between PGRN expression of CRC cells and
expressions of smooth muscle actin alpha (alpha-SMA) on CAFs in CRC patient
tissues. PGRN/alpha-SMA co-expression was positively correlated with CRC patient
poor prognosis. Co-cultured with CRC cells or human recombinant PGRN (rPGRN), the
expression of Ki67, fibroblast activation protein (FAP) and alpha-SMA in
fibroblasts were all up-regulated significantly, accompanying with elevated
cellular proliferation, migration and contraction. Whilst co-cultured with PGRN
silenced CRC cells, these functions were down-regulated. Studies of the
underlying molecular mechanism demonstrated that either tumor necrosis factor
receptor 2 (TNFR2)/Akt or the extracellular regulated kinase (ERK) signaling
pathway contributed to modulate of Ki67, FAP, and alpha-SMA expression, and
correlated to abilities of proliferation, migration and contraction in
fibroblasts. In conclusion, PGRN plays an important role in activation of CRC
fibroblasts, which may be taken as a prospective target of CRC therapy.
PMID- 28412749
TI - Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular
carcinoma.
AB - Recent studies have demonstrated an oncogenic role of the transcription factor
(TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between
CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c
directly interacts with another TF, YY1, which is also overexpressed in multiple
cancers, including HCC. To evaluate if these proteins are co-regulated in
carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136)
tissues and examined the correlation between their expression and
clinicopathological characteristics of HCC. Receiver operating characteristic
analysis exhibited the validity of CP2c and nuclear YY1 expression as a
diagnostic factor in HCC tissues. High expression of CP2c was significantly
correlated with patient age, and higher histological grade, American Joint
Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC
tissues, whereas high expression of nuclear YY1 was significantly associated with
higher AJCC stage and small vessel invasion. In univariate and multivariate
analyses, high expression of CP2c was significantly correlated with disease free
survival (DFS), indicating that CP2c expression is an independent prognostic
factor for DFS in HCC patients. Patients with high expression of both CP2c and
nuclear YY1 usually had a shorter median survival time and worse DFS prognosis
than other patients, suggesting that combined detection of CP2c and nuclear YY1
is a useful prognostic marker in HCC patients.
PMID- 28412751
TI - Poly (ADP-ribose) polymerase inhibitor, an effective radiosensitizer in lung and
pancreatic cancers.
AB - The development of stereotactic body radiation therapy (SBRT) has revolutionized
radiation therapy for lung cancers and is an emerging treatment option for
pancreatic cancers. However, there are many questions on how to optimize its use
in chemoradiotherapy. The most relevant addition to radiotherapy regimens are
inhibitors of DNA repair and DNA damage response pathways. One such class of
agents are inhibitors of poly (ADP-ribose) polymerase (PARP). In this study we
examined the effects of the PARP inhibitor LT626 in combination with ionizing
radiation in lung and pancreatic cancers. Our study demonstrated that combination
treatment with LT626 and radiation effectively inhibited growth in lung and
pancreatic cancer cell lines, better than individual treatment alone. Combination
treatment also increased expression of gammaH2AX and 53BP1 foci and upregulated
expression of phosphorylated ATM, ATR and their respective kinases. Using in vivo
lung cancer xenograft models we demonstrated that LT626 functioned as an
effective radiosensitizer during fractionated radiation treatment, leading to
significant decrease in tumor burden and doubling the median survival compared to
control group. Overall our in vitro and in vivo studies showed that PARP
inhibitor LT626 acted synergistically with radiation in lung and pancreatic
cancers.
PMID- 28412750
TI - microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting
Grb2-associated binding 2 (Gab2).
AB - The expression and biological function of Grb2-associated binding 2 (Gab2) in
renal cell carcinoma (RCC) cells was tested here. We showed that Gab2 expression
was significantly elevated in human RCC tissues and RCC cells. It was correlated
with over-activation of Akt and downregulation of microRNA-302c-3p ("miR-302c
3p"), a putative Gab2-targeting microRNA. Knockdown of Gab2 inhibited Akt
activation and 786-O RCC cell proliferation. Reversely, forced over-expression of
Gab2 led to Akt hyper-activation to facilitate 786-O cell proliferation.
Exogenous expression of miR-302c caused Gab2 downregulation, Akt inhibition and
786-O cell proliferation inhibition. On the other hand, miR-302c-3p depletion by
expressing its anti-sense ("antagomiR-302c") led to Gab2 upregulation, Akt
activation and increased 786-O cell proliferation. Significantly, miR-302c-3p
failed to affect the proliferation of 786-O cells with shRNA-depleted Gab2.
Together, we suggest that miR-302c-3p depletion in human RCC cells leads to Gab2
over-expression, Akt hyper-activation and cell proliferation.
PMID- 28412752
TI - Clinicopathologic implications of immune classification by PD-L1 expression and
CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer
patients.
AB - We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in
gastric cancer (GC), and categorized into 4 microenvironment immune types.
Immunohistochemistry (PD-L1, CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ
hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed
in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based
adjuvant chemotherapy, and two public genome databases were analyzed for
validation. PD-L1+ was found in 98/392 GCs (25.0%). The proportions of immune
types are as follows: PD-L1+/CD8High, 22.7%; PD-L1-/CD8Low, 22.7%; PD-L1+/CD8Low,
2.3%; PD-L1-/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+
and MSI-high (MSI-H) GCs (92.0% and 66.7%, respectively), and genome analysis
from public datasets demonstrated similar pattern. PD-L1-/CD8High showed the best
overall survival (OS) and PD-L1-/CD8Low the worst (P < 0.001). PD-L1 expression
alone was not associated with OS, however, PD-L1-/CD8High type compared to PD
L1+/CD8High was independent favorable prognostic factor of OS by multivariate
analysis (P = 0.042). Adaptation of recent molecular classification based on EBV,
MSI, E-cadherin, and p53 showed no significant survival differences. These
findings support the close relationship between PD-L1/CD8 status based immune
types and EBV+, MSI-H GCs, and their prognostic significance in stage II/III GCs.
PMID- 28412753
TI - Vitamin D increases programmed death receptor-1 expression in Crohn's disease.
AB - BACKGROUND: Vitamin D modulates inflammation in Crohn's disease (CD). Programmed
death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin
D might modulate PD-1 signalling in CD. AIM: To investigate PD-1 expression on T
cell subsets in CD patients treated with vitamin D or placebo. METHODS: We
included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo
and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma
were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and
surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma
levels were measured by ELISA. RESULTS: PD-1 expression upon T cell stimulation
was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19%
(range 10 - 39%) to 29% (11 - 79%)(p = 0.03) compared with placebo-treated
patients. Vitamin D treatment, but not placebo, decreased the expression of the T
cell activation marker CD69 from 42% (31 - 62%) to 33% (19 - 54%)(p = 0.01).
Soluble PD-1 levels were not influenced by vitamin D treatment. CONCLUSIONS:
Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in
response to activation and reduces the CD69 expression in CD patients.
PMID- 28412755
TI - Randomized clinical trial comparing the effects of sevoflurane and propofol on
carbon dioxide embolism during pneumoperitoneum in laparoscopic hepatectomy.
AB - Laparoscopic hepatectomy carries a high risk of gas embolism due to the extensive
hepatic transection plane and large hepatic vena cava. Here, we compared the
influence of inhaled and intravenous anesthetics on gas embolism during
laparoscopic hepatectomy. Fifty patients undergoing laparoscopic hepatectomy were
divided into two groups to receive sevoflurane anesthesia (group S, n = 25) or
intravenous propofol anesthesia (group p, n = 25). During the operation, gas
emboli were detected by transesophageal echocardiography and graded according to
their size. Venous CO2 emboli were detected in all patients, and the embolism
grades did not differ between the two groups. However, the mean embolism episode
duration was longer in group S than group P (51.24+/-23.59 vs. 34.00+/-17.13 sec,
p < 0.05). At the point of the most severe gas embolism, the PTCO2 was higher in
group S than group p (44.00+/-4.47 vs. 41.36+/-2.77 mmHg, p < 0.05), while the
PO2/FiO2 (450.52+/-54.08 vs. 503.80+/-63.18, p < 0.05) and pH values (7.35+/-0.05
vs. 7.38+/-0.02, p < 0.05) were lower in group S than group P. Patients with a
history of abdominal surgery or liver cirrhosis had higher gas embolism grades.
Thus volatile anesthetics may lengthen the duration of embolism episodes and
worsen hemodynamics and pulmonary blood gas exchange during surgery.
PMID- 28412756
TI - Effects of circadian clock genes and environmental factors on cognitive aging in
old adults in a Taiwanese population.
AB - Previous animal studies have indicated associations between circadian clock genes
and cognitive impairment . In this study, we assessed whether 11 circadian
clockgenes are associated with cognitive aging independently and/or through
complex interactions in an old Taiwanese population. We also analyzed the
interactions between environmental factors and these genes in influencing
cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the
Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were
administered to all subjects, and MMSE scores were used to evaluate cognitive
function. Our data showed associations between cognitive aging and single
nucleotide polymorphisms (SNPs) in 4 key circadian clock genes, CLOCK rs3749473
(p = 0.0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and
RORB rs10781247 (p = 7.9 x 10-5). We also found that interactions between CLOCK
rs3749473, NPAS2 rs17655330, RORA rs13329238, and RORB rs10781247 affected
cognitive aging (p = 0.007). Finally, we investigated the influence of
interactions between CLOCK rs3749473, RORA rs13329238, and RORB rs10781247 with
environmental factors such as alcohol consumption, smoking status, physical
activity, and social support on cognitive aging (p = 0.002 ~ 0.01). Our study
indicates that circadian clock genes such as the CLOCK, NPAS2, RORA, and RORB
genes may contribute to the risk of cognitive aging independently as well as
through gene-gene and gene-environment interactions.
PMID- 28412758
TI - Endoscopic diagnosis of primary anorectal melanoma.
AB - OBJECTIVE: The present study retrospectively analyzed case data from 12 patients
diagnosed with anorectal melanoma, with the purpose of identifying key diagnostic
features at endoscopy. MATERIALS AND METHODS: Images from colonoscopy were
reviewed for all patients in order to establish the endoscopic features of
primary anorectal melanoma. For the patients whose colonoscopic examinations
included endoscopic ultrasound, images were examined to characterize lesions and
the depth of infiltration, the results of which were compared with pathological
findings after operative resection. RESULTS: At colonoscopy, superficial melanin
pigmentation was identified in 10 patients with anorectal melanoma, with
morphology including spots, patches, or sheets of pigmentation. In patients who
underwent endoscopic ultrasound, lesions appeared as masses on the mucosal side
with inhomogeneous or low-level internal echoes or ulcer-type lesions invading
the muscularis propria. Lesions diagnosed as anorectal melanoma also demonstrated
irregular margins and varying degrees of submucosal infiltration. Infiltration
depth of melanoma via endoscopic ultrasound (EUS) was concordant with surgical
pathology results in 100% of patients. CONCLUSION: Colonoscopy combined with
biopsy and subsequent pathological examination can accurately diagnose primary
anorectal melanoma. Moreover, EUS is a reliable tool for assessing the depth of
infiltration of this disease.
PMID- 28412760
TI - Left Ventricular Aneurysm May Not Manifest as Persistent ST Elevation on
Electrocardiogram.
AB - BACKGROUND Electrocardiographic presentations of left ventricle aneurysms are
diverse; however, a persistent ST segment elevation post myocardial infarction is
most commonly reported. CASE REPORT The authors present a case of a 67-year-old
man who presented to the emergency department after three days of chest pain and
was found to have an acute myocardial infarction with an incidental finding of a
left ventricular aneurysm. His surface electrocardiogram, however, demonstrated
only inverted T waves in the precordial leads. He had a very elevated serum
troponin I consistent with an acute myocardial injury which prompted a cardiac
catheterization with angioplasty. Post angioplasty, he had persistent T wave
inversions in the precordial leads. CONCLUSIONS It is important for clinicians to
appreciate that the presence of newly inverted T waves in patients with a late
presentation post myocardial infarction should raise a concern for a possible
left ventricular aneurysm.
PMID- 28412757
TI - Fatty acid metabolism in breast cancer subtypes.
AB - Dysregulation of fatty acid metabolism is recognized as a component of malignant
transformation in many different cancers, including breast; yet the potential for
targeting this pathway for prevention and/or treatment of cancer remains
unrealized. Evidence indicates that proteins involved in both synthesis and
oxidation of fatty acids play a pivotal role in the proliferation, migration and
invasion of breast cancer cells. The following essay summarizes data implicating
specific fatty acid metabolic enzymes in the genesis and progression of breast
cancer, and further categorizes the relevance of specific metabolic pathways to
individual intrinsic molecular subtypes of breast cancer. Based on mRNA
expression data, the less aggressive luminal subtypes appear to rely on a balance
between de novo fatty acid synthesis and oxidation as sources for both biomass
and energy requirements, while basal-like, receptor negative subtypes overexpress
genes involved in the utilization of exogenous fatty acids. With these
differences in mind, treatments may need to be tailored to individual subtypes.
PMID- 28412761
TI - Preoperative Assessment of Hepatocellular Carcinoma with Split-Bolus Combined
Phase Contrast-Enhanced Computed Tomography.
AB - BACKGROUND The aim of this study was to investigate the feasibility of a split
bolus combined phase contrast-enhanced computed tomography protocol in evaluation
of liver vasculature in hepatocellular carcinoma (HCC) patients for the purpose
of surgery guidance. MATERIAL AND METHODS Two groups of patients were recruited
for the study: 24 consecutive cases of HCC who underwent multiphasic CT
examination, and 22 consecutive cases who afterwards underwent split-bolus
combined phase CT examination. The multiphasic protocol included an unenhanced
scan and 3 image acquisitions after contrast injection. The injection of contrast
medium was 440 mgI/kg in a single bolus. The split-bolus combined phase protocol
included unenhanced scan and combined phase. The injection of contrast medium was
440 mgI/kg for the first bolus and 220 mgI/kg for the second bolus. The vascular
delineation was evaluated with Likert scales. The CT values were measured, and
the contrast-to-noise ratio (CNR) was calculated. We also compared the effective
radiation dose (ED) of the 2 protocols. RESULTS All mean CT values were
significantly higher in the split-bolus protocol than in the multiphasic protocol
(all P.05). The ED was significantly lower in the split-bolus protocol,
corresponding to a dose reduction of 66% compared to the multiphasic protocol
(P<.05). The scores of the branches of the hepatic vein in the split-bolus
protocol were not lower than those in the multiphasic protocol. CONCLUSIONS For
the preoperative HCC patients, the split-bolus combined phase CT examination
meets the diagnostic requirement of surgical planning, with approximately 60%
reduction in the radiation dose.
PMID- 28412762
TI - Sleep Deprivation and Late Bedtime Impair Sperm Health Through Increasing
Antisperm Antibody Production: A Prospective Study of 981 Healthy Men.
AB - BACKGROUND The aim of this study was to investigate the effects of sleep duration
and bedtime on sperm health, and the possible mechanism involved. MATERIAL AND
METHODS We randomly divided 981 healthy Chinese men into groups according to
research-set bedtimes (A=8-10 PM, B=after 10 PM, and C=after midnight) and sleep
durations: group 1=<6.0 h (short), group 2=7.0-8.0 h (average), and group 3=>9.0
h (long). Sperm morphology, count, survival, and motility were examined according
to sleep patterns. Antisperm antibody (ASA) production in semen was determined.
RESULTS Sperm counts and their survival rates were lower in the short sleepers as
compared to others within each group (all P<0.01). The lower counts and survival
rates were observed in different bedtimes, with significant differences found
between measurements of C1 vs. A1 and C2 vs. A2 or B2 (all P<0.05 or 0.01). Semen
motility was lower in the short sleepers as compared to the average and long
sleepers (all P<0.01). There were differences in the bedtime-related results
between measurements of C1 vs. A1 or B1 (P<0.05 or 0.01). Additionally, the
population proportion for the ASA-positive participates and incidence of the ASA
expressed population obviously increased in the short sleepers as compared to
others within each group (all P<0.05). CONCLUSIONS Short and long sleep durations
and late bedtime were associated with impaired sperm health in the study cohort,
partly through increasing ASA production in the semen.
PMID- 28412763
TI - Altered expression of SDF-1 and CXCR4 during fracture healing in diabetes
mellitus.
AB - PURPOSE: Diabetes mellitus (DM) is known to impair fracture healing. The purpose
of this study was to elucidate and compare the gene expression patterns and
localization of stromal cell-derived factor 1 (SDF-1) and CXC chemokine receptor
4 (CXCR4) during fracture healing of the femur in rats with and without DM.
METHODS: Closed transverse fractures were created in the femurs of rats equally
divided into a DM group and control group; DM was induced by streptozotocin. At
post-fracture days five, seven, 11, 14, 21 and 28, total RNA was extracted from
the fracture callus and mRNA expression levels of SDF-1 and CXCR4 were measured
by real-time polymerase chain reaction. Localization of SDF-1 and CXCR4 proteins
at the fracture site was determined by immunohistochemistry at days 21 and 28.
RESULTS: SDF-1 expression was significantly lower in the DM group than in the
healthy group on days 21 and 28, and showed a significant difference between days
14 and 21 in the healthy group. There was no significant difference in CXCR4
expression levels between the healthy and DM groups at any time point. On day 21
immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site of the
healthy group but no immunoreactivity was observed in the DM group. On day 28,
immunoreactivity of SDF-1 and CXCR4 was detected at the fracture site in both
groups. CONCLUSION: Gene expression and localization of SDF-1 and CXCR4 was
altered during fracture healing, which may contribute to the impaired fracture
healing in DM.
PMID- 28412764
TI - How Networks of Informal Trails Cause Landscape Level Damage to Vegetation.
AB - When visitors are not constrained to remain on formal trails, informal trail
networks can develop and damage plant communities in protected areas. These
networks can form in areas with low growing vegetation, where formal trails are
limited, where there is limited regulation and where vegetation is slow to
recover once disturbed. To demonstrate the extent of impacts from unregulated
recreational use, we assessed damage to alpine vegetation by hikers and pack
animals in the highest protected area in the southern Hemisphere: Aconcagua Park,
in the Andes. Within the 237 ha area surveyed in the Horcones Valley, over 19 km
of trails were found, nearly all of which (94%) were informal. This network of
trails resulted in the direct loss of 11.5 ha of vegetation and extensive
fragmentation of alpine meadows (21 fragments) and steppe vegetation (68
fragments). When levels of disturbance off these trails were quantified using
rapid visual assessments, 81% of 102 randomly located plots showed evidence of
disturbance, with the severity of disturbance greatest close to trails. As a
result, vegetation in 90% of the Valley has been damaged by visitor use, nearly
all of it from unregulated use. These results highlight the extent to which
informal trails and trampling off-trail can cause landscape damage to areas of
high conservation value, and hence the importance of better regulation of visitor
use. The methodology used for off-trail impact assessment can be easily applied
or adapted for other popular protected areas where trampling off-trail is also an
issue.
PMID- 28412765
TI - Advanced Value Chain Collaboration in Ghana's Cocoa Sector: An Entry Point for
Integrated Landscape Approaches?
AB - Value chain analyses have focused mainly on collaboration between chain actors,
often neglecting collaboration "beyond the chain" with non-chain actors to tackle
food security, poverty and sustainability issues in the landscapes in which these
value chains are embedded. Comparing conventional and advanced value chain
collaborations involving small-scale cocoa farmers in Ghana, this paper analyzes
the merits of a more integrated approach toward value chain collaboration. It
particularly asks whether advanced value chain collaboration targeting cocoa
producing areas potentially offers an entry point for implementing a landscape
approach. The findings detail current chain actors and institutions and show how
advanced value chain collaboration has a greater positive impact than
conventional value chain collaboration on farmers' social, human and natural
capital. The paper concludes that the integrated approach, focus on learning, and
stable relationships with small-scale farmers inherent in advanced value chain
collaboration makes it both more sustainable and effective at the local level
than conventional approaches. However, its scope and the actors' jurisdictional
powers and self-organization are too limited to be the sole tool in negotiating
land use and trade-offs at the landscape level. To evolve as such would require
certification beyond the farm level, partnering with other landscape
stakeholders, and brokering by bridging organizations.
PMID- 28412766
TI - Integrative Governance of Environmental Water in Australia's Murray-Darling
Basin: Evolving Challenges and Emerging Pathways.
AB - Integration, a widely promoted response to the multi-scale complexities of social
environmental sustainability, is diversely and sometimes poorly conceptualized.
In this paper we explore integrative governance, which we define as an iterative
and contextual process for negotiating and advancing the common interest. We
ground this definition in a discussion of institutional factors conditioning
integrative governance of environmental water in Australia's Murray-Darling
Basin. The Murray-Darling Basin is an iconic system of social-ecological
complexity, evocative of large-scale conservation challenges in other developed
arid river basins. Our critical assessment of integrative governance practices in
that context emerges through analysis of interviews with policy participants and
documents pertaining to environmental water management in the tri-state area of
southwestern New South Wales, northwestern Victoria, and the South Australian
Riverland. We identify four linked challenges: (i) decision support for
developing socially robust environmental water management goals, (ii) resource
constraints on adaptive practice, (iii) inter-state differences in participatory
decision-making and devolution of authority, and (iv) representative inclusion in
decision-making. Our appraisal demonstrates these as pivotal challenges for
integrative governance in the common interest. We conclude by offering a
perspective on the potential for supporting integrative governance through the
bridging capacity of Australia's Commonwealth Environmental Water Holder.
PMID- 28412767
TI - Herbage intake and milk yield in Comisana ewes as effect of 4 vs 7 h of grazing
during late lactation.
AB - Thirty-two Comisana ewes at late lactation were used in two trials carried out
during late spring in 2 consecutive years, with the aim to evaluate the effect of
the duration of grazing on herbage intake and performance. In each trial, 16
pluriparous Comisana lactating ewes were equally divided into two groups which
grazed in two separate areas of natural pasture from 11:00 to 15:00 h (group 4H)
or from 10:00 to 17:00 (group 7H). A concentrate mixture (500 g/day) was also
offered to each ewe. The mean maximum temperature was, respectively, 23.5 +/- 3.8
degrees C during experiment 1 and 27.0 +/- 3.1 degrees C during experiment 2.
Probably as a consequence of the differences in climatic conditions, the results
on herbage intake and milk production were different during the two trials.
Herbage dry matter intake was not affected by the duration of grazing during
trial 1, whereas it was significantly lower in 4H group compared to that in 7H
group (0.67 vs 1.02 kg/day; P < 0.001) during trial 2. It could be hypothesised
that while with lower environmental temperature (trial 1), the 4H ewes were able
to reach good intake levels despite grazing during the hottest hours; with higher
temperatures throughout the trial (trial 2), the 4H ewes reduced ingestion. Milk
production was higher in 4H group during trial 1 (778 vs 707 g/day; P = 0.006),
whereas it was not affected by the number of hours of grazing during trial 2,
despite the higher intake levels reached by the 7H group. In conclusion, 3 extra
hours of grazing for ewes at late lactation on a low quality pasture could be
nullified in terms of yield response.
PMID- 28412768
TI - Assessing the dispersive and electrostatic components of the selenium-aromatic
interaction energy by DFT.
AB - Selenium has been increasingly recognized as an important element in biological
systems, which participates in numerous biochemical processes in organisms,
notably in enzyme reactions. Selenium can substitute sulfur of cysteine and
methionine to form their selenium analogues, selenocysteine (Sec) and
selenomethionine (SeM). The nature of amino acid pockets in proteins is dependent
on their composition and thus different non-covalent forces determine the
interactions between selenium of Sec or SeM and other functional groups,
resulting in specific biophysical behavior. The discrimination of selenium toward
sulfur has been reported. In order to elucidate the difference between the nature
of S-pi and Se-pi interactions, we performed extensive DFT calculations of
dispersive and electrostatic contributions of Se-pi interactions in substituted
benzenes/hydrogen selenide (H2Se) complexes. The results are compared with our
earlier reported S-pi calculations, as well as with available experimental data.
Our results show a larger contribution of dispersive interactions in Se-pi
systems than in S-pi ones, which mainly originate from the attraction between Se
and substituent groups. We found that selenium exhibits a strong interaction with
aromatic systems and may thus play a significant role in stabilizing protein
folds and protein-inhibitor complexes. Our findings can also provide molecular
insights for understanding enzymatic specificity discrimination between single
selenium versus a sulfur atom, notwithstanding their very similar chemical
properties.
PMID- 28412769
TI - Applicability of geochemical techniques and artificial sweeteners in
discriminating the anthropogenic sources of chloride in shallow groundwater north
of Toronto, Canada.
AB - Elevated levels of chloride concentration due to anthropogenic activities
including the road salts, septic effluent and agricultural sources are common in
shallow groundwater of the recent glacial deposits north of Toronto, Ontario,
Canada. Identifying suitable techniques for discriminating the source of the
chloride concentration helps to better plan the protection of groundwater in the
area. This paper examines the applicability of geochemical techniques with
emphasis on Panno et al. (Ground Water 44: 176-187, 2006) and Mullaney et al.
(2009) graphical approaches for discriminating the sources of chloride with known
causes of impacts. The results indicated that the graphical methods developed
using Cl-, Br- and/or total nitrogen (N) could identify the combined sources of
road salts and septic systems. However, discriminating between the road salts,
septic effluent or agricultural sources needs to be complemented by other
techniques including the artificial sweeteners and isotope tracers.
PMID- 28412770
TI - Anemia in chronic kidney disease.
AB - Anemia is common and associated with adverse outcomes in children with chronic
kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD
progresses, but impaired production of erythropoietin by failing kidneys is a
central cause. Hepcidin-mediated iron restriction also contributes to anemia by
downregulating both intestinal iron absorption and release of stored iron for
erythropoiesis. The core components of anemia management remain erythropoiesis
stimulating agents (ESA) and iron supplementation, but despite these therapies, a
substantial number of children remain anemic. Although escalating ESA dose to
target higher hemoglobin has been associated with adverse outcomes in adults, no
trials have investigated this association in children, and maintaining hemoglobin
levels in a narrow range with conservative ESA dosing is challenging. Judicious
use of iron supplementation can enhance the response to ESAs, but the iron
storage markers most commonly used in clinical practice have limitations in
distinguishing which patients will benefit most from additional iron. Several
novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl
hydroxylase inhibitors, and dialysate-delivered iron supplements, have been
developed and may offer options for alternative anemia management. However, the
safety and efficacy of these agents in children with CKD has yet to be assessed.
PMID- 28412771
TI - Drug cue reactivity involves hierarchical instrumental learning: evidence from a
biconditional Pavlovian to instrumental transfer task.
AB - RATIONALE: Drug cue reactivity plays a crucial role in addiction, yet the
underlying mechanisms are poorly understood. According to the binary associative
account, drug stimuli retrieve an expectation of the drug outcome, which, in
turn, elicits the associated drug-seeking response (S-O-R). By contrast,
according to the hierarchical account, drug stimuli retrieve an expectation that
the contingency between the drug-seeking response and the drug outcome is
currently more effective, promoting performance of the drug-seeking response (S:R
O). METHODS: The current study discriminated between these two accounts using a
biconditional Pavlovian-to-instrumental transfer (PIT) task with 128 alcohol
drinkers. A biconditional discrimination was first trained in which two responses
produced alcohol and food outcomes, respectively, and these response-outcome
contingencies were reversed across two discriminative stimuli (SDs). In the PIT
test, alcohol and food cues were compounded with the two SDs to examine their
impact on percent alcohol choice in extinction. RESULTS: It was found that
alcohol and food cues selectively primed choice of the response that earned that
outcome in each SD (p < .001), and this effect was associated with participants'
belief that cues signalled greater effectiveness of that response (p < .0001).
CONCLUSIONS: The alcohol stimulus could not have selectively primed the alcohol
seeking response through binary S-O-R associations because the drug outcome was
equally associated with both responses. Rather, the alcohol stimulus must have
retrieved an expectation that the response-alcohol contingency available in the
current context was more likely to be effective (S:R-O), which primed performance
of the alcohol-seeking response.
PMID- 28412772
TI - Quantitative analysis of external limiting membrane, ellipsoid zone and
interdigitation zone defects in patients with macular holes.
AB - PURPOSE: To investigate the correlation between the length of external limiting
membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) defects and
visual prognosis in patients undergoing macular hole (MH) surgery, using spectral
domain optical coherence tomography (SD-OCT). METHODS: This is a retrospective,
consecutive, observational case series study. Fifty-two eyes of 52 patients with
primary MH were evaluated. A quantitative analysis of ELM, EZ and IZ defects was
performed preoperatively and at 3 and 6 months postoperatively using SD-OCT. The
correlation between pre- and postoperative ELM, EZ and IZ defects and the best
corrected visual acuity (BCVA) was investigated. RESULTS: The lengths of ELM, EZ
and IZ defects correlated significantly with BCVA in each study period (P <
0.001). Preoperative measures of these band defects were also associated with
visual outcomes 3 and 6 months after surgery (P < 0.05). Considering all
preoperative parameters, the length of the ELM defect was the factor most
strongly correlated with BCVA at 6 months (beta = 0.643, P < 0.012). The
integrity of the ELM was the only factor significantly associated with BCVA at 6
months (beta = 0.427; P = 0.004). CONCLUSIONS: The preoperative length of the ELM
defect is the strongest predictor of visual acuity after MH surgery.
Postoperative integrity of the ELM is significantly associated with visual
restoration after surgical treatment of MH.
PMID- 28412774
TI - Treating the Patient, Not the Disease: Fred Schiffman on Humanism in Medicine.
PMID- 28412773
TI - Massive subretinal and subretinal pigment epithelial hemorrhage displacement with
perfluorocarbon liquid using a two-step vitrectomy technique.
AB - PURPOSE: The purpose of this study was to evaluate the efficacy and visual
outcome of massive submacular hemorrhage (SMH) displacement with a planned two
step pars plana vitrectomy (PPV) using tissue plasminogen activator (tPA) and
perfluorocarbon liquid (PFCL) tamponade. METHODS: A retrospective case series of
patients with age related macular degeneration and SMH was used. All patients
underwent a 23G PPV, subretinal tPA injection and a medium term PFCL tamponade. A
second stage PPV for PFCL removal was performed 7-17 days later. The main outcome
was the change in macular and sub-RPE thickness after 6 months. Secondary
outcomes were visual acuity and complications. RESULTS: Seven patients (seven
eyes) with mean age of 79.85 years were enrolled. The average SMH size was 17.5
disc area (range 4.5-33) with mean symptoms of a duration of 9.5 days (range: 2
21). SMH was successfully displaced in six eyes. Mean macular and sub-RPE
thickness decreased from 1505MU to 711.3MU and 900 MU to 457MU, respectively.
Visual acuity (VA) remained stable in five eyes. Complications included corneal
edema and transient intraocular pressure elevation in three patients.
CONCLUSIONS: SMH displacement using subretinal tPA injection and medium term PFCL
tamponade is an effective alternative treatment option. In our experience, it can
be safely performed, avoiding complications commonly attributed to other
techniques.
PMID- 28412775
TI - Defining Value in Radiation Oncology: Approaches to Weighing Benefits vs Costs.
AB - The passage of the Affordable Care Act in 2010 initiated discussion regarding
transitioning from a fee-for-service arrangement of care reimbursement to value
based care. Cost-effectiveness analysis (CEA) has been used in the past to
quantify value as it relates to the provision of healthcare. New treatments or
techniques being compared with other new or existing therapies or approaches to
care were determined to be cost-effective if the incremental cost-effectiveness
ratio was less than $50,000/life-year or quality-adjusted life-year. This result
was accepted as a proxy for value in care delivery. The calculation of value,
however, is the inverse of CEA, with units measured in outcome/cost. Given the
wealth of medical information now available online, patients are becoming more
sophisticated consumers of healthcare, investigating not only outcomes but also
costs of care associated with different treatment approaches. Costs to be
considered include direct medical costs; the indirect medical costs associated
with treatment; and productivity costs resulting, for example, from time lost
from work when patients must travel to a cancer center or clinic to receive
treatment. Radiation oncologists must be mindful of these costs when designing
treatment plans. Increased adoption of hypofractionated radiation treatment
strategies (ie, higher radiation doses given over a shorter course of treatment)
could increase patient value by reducing direct and indirect medical costs, as
well as productivity costs.
PMID- 28412776
TI - Defining the Value Research Agenda in Radiation Oncology.
PMID- 28412777
TI - How to Address Sexual Problems in Female Cancer Patients.
AB - Sexual health is an important aspect of human life, and cancer does not (and
should not) change that. Data suggest that issues related to sexual function are
quite common among women treated for cancer. However, clinicians often spend
little to no time on the topic. This article provides a concise summary on the
importance of sexual health among women treated for cancer, as well as an
approach that general cancer clinicians can adopt in order to normalize sexual
health issues for their patients. Finally, we provide an overview of sexual
health therapeutics available in the United States and in Europe.
PMID- 28412778
TI - PARP Inhibitors: The Cornerstone of DNA Repair-Targeted Therapies.
AB - The activity and therapeutic licensing of poly(ADP-ribose) polymerase (PARP)
inhibitors is the culmination of 50 years of research. However, the biology,
mechanisms of action, adequate treatment combinations, and targeted populations
for these agents need to be explored further. PARP activity is essential for the
repair of single-strand DNA breaks via the base excision repair pathway. This
pathway is the default repair pathway in cells with deficient high-fidelity
double-strand break homologous recombination (HR) repair, such as occurs with
loss of BRCA1 or BRCA2 function. Therefore, inhibition of PARP function results
in cell death in HR-deficient tumors, and sensitizes tumor cells to cytotoxic
agents that induce DNA damage. Applications of PARP inhibition are now being
expanded beyond tumors with HR deficiency-to HR-competent tumors in which HR has
been synthetically impaired through use of other agents given in combination with
PARP inhibitors, or resulting from PARP inhibition in the setting of BRCA1 or
BRCA2 loss.
PMID- 28412779
TI - Synchronous Bilateral Breast Cancer With Discordant Histology.
PMID- 28412780
TI - How Can We Effectively Address the Medical and Psychological Concerns of
Survivors of Pelvic Malignancies?
AB - Sexual and urinary morbidities resulting from treatment of pelvic malignancies
are common. These treatment sequelae are significantly bothersome to patients and
challenging to address. Awareness of these complications is critical in order to
properly counsel patients regarding potential side effects and to facilitate
prompt diagnosis and management. Addressing these issues often necessitates a
coordinated multidisciplinary approach; however, the effort required often
translates into improvement in patient quality of life. Herein we review the
sexual and urinary side effects that may arise during or after treatment of
pelvic malignancies.
PMID- 28412781
TI - Molecular Testing to Optimize and Personalize Decision Making in the Management
of Colorectal Cancer.
AB - Recent improvements in our understanding of the biology of colorectal cancer have
led to the identification of several important prognostic and predictive markers
of disease-associated risk and treatment response for the individual patient.
Proper utilization of these biomarkers can enable physicians to tailor
therapeutic strategies to maximize the likelihood of response and minimize
treatment toxicity. In the management of colorectal cancer, tremendous progress
has been made in the development of strategies for immune checkpoint inhibition;
in refinement of agents and approaches used in targeted therapy; and in
techniques for molecular subtyping of tumor samples that have identified patient
subgroups with clinically relevant cellular differences potentially affecting
clinical management and treatment outcome. In this article, we discuss several of
the commonly tested markers in colorectal cancer-including microsatellite
instability, RAS/RAF, DPD, HER2, UTG1A1, TS, and Immunoscore-and highlight their
prevalence, prognostic and predictive value, and current role in the overall
treatment paradigm.
PMID- 28412782
TI - [Digital medical techniques play an important role in the development of oral and
maxillofacial surgery].
PMID- 28412783
TI - [Paying attention to the protection of the function organ of submandibular
gland].
AB - Submandibular gland is an important human function organ. With the wide
application of sialoendoscope and new understanding of IgG4 related sialadenitis,
a lot of submandibular glands which were previously considered to be removed are
preserved. However, some submandibular glands which might be preserved are still
unfortunately sacrificed. Therefore, we advocate the popularization and promotion
of new knowledge and techniques and should pay more attention to the protection
of the function organ of submandibular gland.
PMID- 28412784
TI - [Three-dimensional printing and oral medicine].
AB - After 30 years of development, three-dimensional printing technology has made
great progress, and the model and surgical guide have been clinically applied.
The three-dimensional printing of titanium and other metal prosthesis and dental
crown after adequate research will be applied clinically, and three-dimensional
bioprinting and related biological materials need further study. Three
dimensional printing provides opportunities for the development of oral medicine,
which will change the way of clinical work, teaching and research. The dentists
should integrate multi-disciplinary knowledge and understand the essence of new
technology to meet the challenges of the era of digital medicine.
PMID- 28412785
TI - [Functional repair of cleft lip: from anatomical resetting to biomechanical
simulation].
AB - We are no longer entangled in the anatomical resetting of the labial-nasal muscle
itself, but the sight to the muscle fiber level, to study the relationship
between the muscle fiber force line and the labial-nasal shape. In the past ten
years, we focused on the lip of nasal muscle fiber anatomy, imageology and
biomechanics, carried out a series of research works, realized the three
dimensional (3D) visualization of small labial-nasal muscle fiber, established
configuration models of normal and cleft lip with nasal muscle fibers, and put
forward the hypothesis of naso-labial muscle tension band. According to the
biomechanical parameters of lip nasal muscle, cartilage, skin and subcutaneous
tissue, we initially established a biomechanical model elaborating the
relationship between labial-nasal muscle tension lines and surface morphology; we
summed up three muscle tension group which determines labial-nasal contour,
explained the biomechanical mechanism in cleft lip and various lip nasal
deformities, and realized the possibility to freely change the 3D labial-nasal
contour by lip nasal lip nasal muscle tension theory; Finally we carried out
clinical validation in clinical treatment of cleft lip, achieved the effect of
detail cleft lip repairing.
PMID- 28412786
TI - [Oral and maxillofacial surgery residency training in the United States: what can
we learn].
AB - China is currently in the process of establishing formal residency training
programs in oral and maxillofacial surgery and other medical and dental
specialties. Regulatory agencies, and educational and academic institutions in
China are exploring mechanisms, goals and standards of residency training that
meet the needs of the Chinese healthcare system. This article provides an
introduction of residency training in oral and maxillofacial surgery in the
United States, with emphasis on the accreditation standard by the Commission on
Dental Accreditation. As there are fundamental differences in the medical and
dental education systems between China and United States, the training standards
in the United States may not be entirely applicable in China. A competency-based
training model that focus on overall competencies in medical knowledge, clinical
skills and values at the time of graduation should be taken into consideration in
a Chinese residency training program in oral and maxillofacial surgery.
PMID- 28412787
TI - [Progress in studies on the genetic risk factors for nonsyndromic cleft lip or
palate in China].
AB - Cleft lip and palate is the most common congenital defects of oral and
maxillofacial region in human beings. The etiology of this malformation is
complex, with both genetic and environmental causal factors are involved. To
provide a better understanding in the genetic etiology of cleft lip or palate,
the author summarized recent years studies based on Chinese population. Those
researches included validation of some candidate genes for cleft lip or palate,
using genome wide association analysis which included six independent cohorts
from China to elucidate the genetic architecture of non-syndromic cleft lip with
or without cleft palate in Chinese population and finally found a new
susceptibility locus. This locus was on the 16p13.3 (rs8049367) between CREBBP
and ADCY9. It has been mentioned common methods of genetic analysis involved in
the researches on cleft lip or palate in this paper. Furthermore, we try to
discuss new methods to illustrate the etiology of cleft lip and palate that could
provide more inspiration on future researches.
PMID- 28412788
TI - [Guidelines for the use of sialendoscopy in salivary gland diseases].
AB - Salivary gland disease is a common disease in oral clinical care. Sialendoscopy
technique has been widely used in salivary gland disease in recent years.
Compared with traditional treatment, it is a safe, minimally-invasive and cost
effective technique, thus presenting significant benefits both for the patient
and the health-care system. As for providing a comprehensive and updated source
of current information on sialendoscopy, it's important to standardize the
operating processes for salivary gland sialendoscopy. Experts from Chinese
Stomatological Association have made a guideline about diagnosis and treatment of
salivary gland disease by sialendoscopy, based on domesticpractical experience
and international reports.
PMID- 28412789
TI - [Development and preliminary clinical application of home-made temporomandibular
joint prostheses].
AB - Objective: To explore the clinical application of home-made temporomandibular
joint (TMJ) prostheses. Methods: Self-developed TMJ prostheses were applied for
end stage osteoarthritis, TMJ ankylosis, condylar tumors after biomechanical
examination. The stability of the prostheses toward bone was evaluated during
operation. Post-operative CT scans and clinical follow-ups were taken to check
changes of mouth opening, position of the prostheses, bone resorption around the
screws, and heterotopic bone formation around artificial condyle. Results: There
were 6 patients accepted 7 prostheses smoothly without infection and other
complications. Post-operative follow-ups were from 6 to 13 months with a mean of
7.6 months. Mouth opening was significantly improved from (16.2+/-14.4) mm before
operation to (31.5+/-4.8) mm during follow-ups (P=0.01). All prostheses were
stable without screw loose and heterotopic bone formation. Conclusions: Home-made
TMJ prostheses were stable after primary clinical application, but the long-term
results need to be observed.
PMID- 28412790
TI - [A preliminary study of three-dimensional bio-printing by polycaprolactone and
periodontal ligament stem cells].
AB - Objective: To investigate the technical scheme of three-dimensional (3D) bio
printing by polycaprolactone (PCL) and periodontal ligament stem cells (PDLSC).
Methods: To manufacture a 3D bio-printing body, PDLSC were used as seed cells,
and polycaprolactone (PCL) was used as the 3D printing scaffold material. Print
size was designed at 13.0 mm*13.0 mm, and mesh size was 0.25 mm*0.25 mm (group A)
and 0.75 mm*0.75 mm (group B). Cell counting kit-8 was used to detect the
proliferation of PDLSC on day 1, day 3 and day 5 respectively. The state of the
cells in the 3D printing structure was observed by scanning electron microscope
(SEM). Osteoblastic ability of the 3D printing mixture was observed after 14 days
of culture by alizarin red mineralized nodule staining method. Results: Using
PDLSC as seed cells and PCL as a scaffold to print two mesh-sized 3D bodies. The
body thickness and porosity of group A and group B were 1.1 mm, 1.5 mm and 49.3%,
72.5% respectively. SEM showed that PDLSC proliferated significantly on two sets
of 3D structure which was more obvious in group A. In vitro osteogenic induction,
a large number of red mineralized nodules formed on the 3D structure.
Conclusions: A 3D structure with a self-defined shape and size was successfully
printed using 3D bio-printing equipment. PDLSC can grow and proliferate on the
structure.
PMID- 28412791
TI - [Surface roughness and gloss of novel flowable composites after polishing and
simulated brushing wear].
AB - Objective: To investigate surface properties of novel flowable composites after
polishing and simulated brushing wear, compared to their pasty counterpart.
Methods: Composites employed in this study were: three flowable composites (A1:
Clearfil Majesty ES Flow; B1: Beautifil Flow Plus F00; C1: Filtek Bulk Fill) and
three paste composites (A2: Clearfil Majesty; B2: Beautifil; C2: Filtek Z350.
Eleven disk-shaped specimens were made for each material. The specimens were
cured, then subjected to sandpaper finishing for 20 s, one-step polishing for 30
s, finally subjected to simulated brushing for 10 000 cycles. Surface roughness
and glossiness were measured before finishing, after finishing, after polishing,
after 5 000 brushing cycles and after 10 000 brushing cycles, respectively. Data
obtained were analyzed using two-way ANOVA method. Scanning electron microscope
was employed to examine the microscopic appearance of each material. Results:
Surface roughness (0.11~0.22 MUm) and glossiness (74.25~86.48 GU) of each
material were similar after one-step polishing. After brushing simulation,
roughness increased significantly and glossiness decreased significantly for each
material (P<0.05). Group A1 presented the best gloss ([50.68+/-1.58] GU) after
final wear (P<0.05). Flowable composites of group A1 and B1 tested in the present
setup showed better surface properties compared to their pasty counterpart (group
A2 and B2). Conclusions: Within the limit of this study, flowable composites
tested in the present research can obtain similar surface polish or even better
than the paste composite counterpart.
PMID- 28412792
TI - [Isolation of cariogenic Streptococcus mutans and the inhibitory effect of egg
yolk antibody on caries].
AB - Objective: To isolate the cariogenic Streptococcus mutans (Sm) strains and study
the therapeutical effect of egg yolk antibody (IgY) of the Sm on dental caries
development. Methods: Sm strains were isolated from the children's dental plaque
samples. Morphological, biochemical and molecular biological methods were applied
to identify the serotype, acid producing and adhesion abilities of isolated Sm
strains. After inactivation one of the Sm strains was used as antigen to immune
laying hens to collect and extract the specific anti-Sm IgY. The rats were
infected with Sm (serotype e). After 16 weeks of infection, all the rats were
found developing dental caries. The rats were then randomly divided into two
groups. The rats in experimental group were supplied with diet containing anti-Sm
IgY while the rats in control group with normal IgY. All rats were sacrificed
after another 8 weeks' observation. The degree of caries for each rat was
assessed using Keyes' method. Results: We isolated 7 Sm strains from the
children's dental plaque samples in the present study. The numbers of serotype c,
e, f, k were 3, 2, 0 and 2, respectively. All strains showed similar
morphological and biochemical characters as standard UA159 Sm strain, and
possessed strong capabilities of acid production and adherence. Interestingly,
even the same serotypec strains, such as No.3 and No.7 strains, demonstrated
significant difference on acid producing and adherence capabilities. After 16
weeks infection with serotype e strain, the rats' mandibular teeth were
apparently decayed, and treatment with specific anti-Sm IgY obviously attenuated
the development of caries in the experiment group rats (16.4+/-2.0) compared with
that in the control group rats (30.2+/-9.3) (P<0.05) determined by Keyes' method.
Conclusions: Seven cariogenic Sm strains of different serotypes were isolated,
which possesses similar morphology and biochemical characters. Although belonging
to the same serotype strains they always show significant difference in acid
producing and adherencec apabilities. Further experiment provides evidences that
the serotype e strain could obviously induce caries independently, and employment
of specific anti-Sm IgY as passive immunotherapy additive might effectively
inhibit the further development of dental caries.
PMID- 28412793
TI - [The effect of restraint stress on masseter mechanical hyperalgesia and the
activity of neurons and astrocytes in the spinal trigeminal nucleus caudalis in
rats].
AB - Objective: To investigate the effect of restraint stress on masseter mechanical
hyperalgesia and the activity of neurons and astrocytes in the spinal trigeminal
nucleus caudalis (Vc). Methods: The animals were randomly divided into the
control group, 1-, 3-, 5-, 7-, 9-, 11-and 14-day stress groups, with 10 rats in
each group. The body weight increase and behavior tests were used to testify the
animal model. The mechanical sensitivity of masseter of the rat before and after
the stress was measured with Von Frey filaments. Histological examinations were
used to evaluate the expression of neuronal c-fos and astrocytic glial fibrillary
acidic protein (GFAP). Results: Restraint stress resulted in remarkable
mechanical allodynia in the masseter muscle. The head withdrawal threshold was
significantly lower in the 7-, 9-, 11-and 14-day stress groups ([0.071+/-0.011],
[0.059+/-0.020], [0.052+/-0.011], [0.033+/-0.011] N) than that in the control
group ([0.120+/-0.025] N) (P<0.05). Compared to the control group, the rats in
the 1-day stress group showed a significant increase of c-fos in neurons of the
Vc and then declined to normal level after 1 week gradually. The GFAP expression
in astrocytes of the Vc was significantly increased in the 7-, 9-, 11-and 14-day
stress groups (4.3+/-1.0, 4.5+/-0.6, 4.6+/-0.5, 4.8+/-1.3) compared with the
control group (2.0+/-0.8) (P<0.05). Conclusions: Chronic restraint stress could
lower the threshold of mechanical allodynia in the masseter muscle and activate
the neurons and astrocytes in Vc. The activation of neurons and astrocytes plays
an important role in the masseter hyperalgesia induced by restraint stress in
rats.
PMID- 28412795
TI - [Pay attention to the complexity of cataract surgery of no vitreous eyes].
AB - With wide-spread performance of pars plana vitrectomy, cataract surgeries with no
vitreous are getting more and more. This kind of surgery has great difference
between individuals and it lacks randomized large sample clinical trial. Surgical
strategy decision was basically relied on the surgeon's personal experience. We
should fully aware the individual and common characteristics of no vitreous
cataract surgery. Surgical time should be carefully decided. Complete ocular
examination, evaluation, design of cataract surgical procedure and appropriate
intra-ocular lens selection are needed. We must pay highly attention on the
cataract surgery of no vitreous eyes. (Chin J Ophthalmol, 2017, 53: 241-243).
PMID- 28412794
TI - [Effects of alginate/collagen scaffold on cell proliferation and differentiation
of human adipose-derived mesenchymal stem cells].
AB - Objective: To build scaffold materials with different concentrations of alginate
and collagen, and to observe the effects of alginate/collagen ratio on the
proliferation of human adipose-derived mesenchymal stem cells (hAMSC) and
osteogenic differentiation. The optimal concentration of alginate/collagen will
be chosen for constructing hydrogel that will be used for bone tissue
engineering. Methods: Soluble hydrogel scaffold materials containing
alginate/collagen were prepared, and the following groups were established based
on different alginate/collagen ratio: 4?1 (group A), 2?1 (group B), and 1?1
(group C). Cell proliferation on the material surface was observed using the cell
counting kit-8 (CCK-8) assay, while cell viability in each material group were
observed using live/dead staining. Quantitative real-time PCR(qPCR) was used to
measure the differential expression of osteogenesis-related genes on and in the
materials. Immunofluorescence staining was used to measure the differential gene
expression of osteogenesis-related proteins in each group. Results: The results
from the CCK-8 assay showed increasing cell proliferation rate on the lyophilized
hydrogel material surface as the collagen concentration increased, and the
highest cell proliferation was observed in group C. Live/dead staining assay
indicated that cells were able to proliferate in all three types of hydrogel
materials, and the highest cell viability was found in material from group B
([87.50+/-2.65]%). qPCR showed that the expression of osteogenesis-related genes
in group C was the highest, among the three groups, while the expression of
osteocalcin in group B was significantly higher than those in the other two
groups (P<0.05). Immunofluorescence staining was carried out for osteocalcin on
and in the hydrogel material and the results were consistent with that of qPCR.
Conclusions: The alginate/collagen scaffold materials did not show adverse
effects on the cell proliferation of hAMSC and osteogenenic differentiation. Bone
tissue engineering can use 10% hydrogel material, and when the sodium alginate
and collagen have a ratio of 2?1, the hydrogel can be conducive to cell
differentiation and proliferation.
PMID- 28412796
TI - [Multiple issues in multifocal intraocular lens].
AB - The occurrence of multifocal intraocular lens (MIOL) is known as an important
period in the development of cataract surgery, which can provide a simultaneous
vision without the use of spectacles or contact lenses. However, in the current
stage, MIOL implantation may also lead to decreased visual acuity and increased
risk of photic phenomena, thus in some instance a second procedure to exchange
the MIOL is necessary. Optimizing visual outcomes of MIOL implantation and
controlling adverse effects has become the focus for ophthalmologists. In the
future, a more remarkable, flexible and high cost-effective intraocular lens
(IOL), which can mimic human natural crystalline lens, should emerge. (Chin J
Ophthalmol, 2017, 53: 244-248).
PMID- 28412797
TI - [Correlation between axial length and corneal curvature and spherical
aberration].
AB - Objective: To discuss the correlation between axial length and corneal curvature
and corneal spherical aberration in a group of cataract patients with axial
length greater than 24 mm. Methods: Retrospective case series. This study
comprised 117 (234 eyes) age-related cataract patients. There were 51 men
(43.59%) and 66 women (56.41%) with mean age of (69.0+/-8.7) years (range from
52.0 to 85.0 years). The average axial length was 27.6+/-1.8 (range from 24.2 to
31.9 mm). We devided them into four groups according to the axial length. A-scan
was used to measure the axial length and Pentacam was used to get the corneal
curvature and corneal spherical aberration of both anterior and posterior
surface. kolmogorov-smirnov test was used to check the normal distribution. ANOVA
test was used to compare eachcorneal parameter among different groups. Pearson
correlation analysis was used to obtain the correlation of corneal parameters in
groups. Results: There were correlations between the axial length and the
anterior and posterior corneal curvature (r=-0.213, r=0.174, respectively,
P<0.05). No correlation was found between the axial length and anterior or
posterior corneal spherical aberration (r=-0.114, 0.055, respectively, P>0.05).
Mean values of corneal anterior surface curvature were (45.26+/-1.60) D (group
1), (44.17+/-1.45) D (group 2), (44.40+/-1.99)D (group 3), and (44.53+/-1.69) D
(group 4) respectively. Mean values of corneal posterior surface curvature were(
6.57+/-0.26)D (group 1), (-6.40+/-0.24)D (group 2), (-6.41+/-0.38)D (group 3),
and (-6.43+/-0.26)D (group 4) respectively. There were significant difference of
corneal anterior and posterior surface curvature among 4 groups (P=0.004,
P=0.001). There was significant difference of corneal curvature of anterior
surface in group 1 compared to group 2 and group 3(P<0.01, P=0.01). There was
significant difference of curvature of posterior surface in group 1 compared to
group 2 and group 3, respectively (P<0.01). Mean values of anterior surface
corneal spherical aberration were (2.09+/-0.53) MUm (group 1), (1.90+/-0.44) MUm
(group 2), (2.00+/-0.74) MUm (group 3), and (1.78+/-0.52) MUm (group 4)
respectively. Mean values of posterior surface corneal spherical aberration were
(2.69+/-1.15) MUm (group 1), (2.46+/-1.16) MUm (group 2), (2.92+/-2.51) MUm
(group 3), and (2.69+/-1.13) MUm (group 4) respectively. No correlation was found
in anterior and posterior surface corneal spherical aberration(P>0.05) among
different groups. Conclusions: The eye with a longer axial length have a flatter
cornea. Cornea fails to compensate for axial length elongation when the axial
length is longer than 28mm. The corneal spherical aberration varies among
individuals, which suggests us to do the customized measurement before cataract
surgery to make a decision on choosing the aspherical intraocular lens. (Chin J
Ophthalmol, 2017, 53: 255-259).
PMID- 28412799
TI - [Long-term outcomes after cataract surgery in infants with congenital cataract].
AB - Objective: To observe the long-term outcomes after congenital cataract surgery
performed prior to 36 months of age. Methods: A retrospective case study was
conducted. Thirty-two cases (57 eyes) of congenital cataract were included from
January 2004 to January 2012. All patients received intraocular lens (IOL)
implantation with posterior continuous curvilinear capsulorhexies and anterior
vitrectomy after cataract extraction and were followed up. At the last visit, the
best corrected visual acuity (BCVA) was determined and postoperative
complications were evaluated during follow-up with a longest time of 13 years.
Non-normal distribution showed in median M (minimum and maximum). Data were
analyzed by Kruskal Wallis single factor variance analysis and multiple
comparison. The independent Mann-Witney U test was used to analyze non-normal
distribution data. Results: There were thirty-two cases (57 eyes) of congenital
cataract including 7 unilateral cases and 25 bilateral cases. The median age at
cataract extraction was 6.0months; the median IOL implantation age was 28.0
months and the median duration of follow-up after cataract extraction was 67.0
months. The median postoperative BCVA was (LogMAR) 0.52. Unilateral and bilateral
cataract postoperative BCVA difference had no statistical significance (U=107,
P>0.05). Patients received cataract surgery in 2 to 4 months, the postoperative
BCVA was better than in 5 to 8 months. The difference was statistical
significance (H=-15.33, P<0.05). BCVA after IOL implantation before 24 months
were significantly better than after 30 months. The difference had statistical
significance(H=-20.61,-20.78, P<0.05). Postoperative complications were posterior
capsular opacity (5 eyes; 8.77%), glaucoma (2 eyes; 3.51%), strabismus (17 eyes;
29.82%) and nystagmus (30 eyes; 52.63%). Conclusions: Most infantile cataract
surgeries performed prior to 36 mouths of life together with the implantation of
IOL can achieve good visual acuity. No serious complications occurred. (Chin J
Ophthalmol, 2017, 53: 266-273).
PMID- 28412798
TI - [Intraocular lens power calculation for high myopic eyes with cataract:
comparison of three formulas].
AB - Objective: To compare the accuracy of three different formulas for intraocular
lens power calculation in high myopic eyes with cataract and analyze their
influencial factors. Methods: One hundred and three high myopic patients of
cataract (103 eyes), with average age of 60.2+/-8.8 years old (39.0-77.0),
including 45 male and 54 female and with axial length >= 26 mm were enrolled in
this retrospective case-series study. All of them underwent routine ocular
examination and IOLMastermeasurement preoperatively and then underwent
phacoemulsification through temporal clear-corneal incision with implantation of
HumanOptic posterior chamber Intraocular lens (IOL). All analyses were conducted
using SPSS version 19.0. Repeated-measures analysis of variance was applied to
compare the refractive results one month postoperatively with the predicted IOL
powers calculated by SRK/T, Holladay 1, or Haigis formula before surgery. The
differences were further compared based on different grouping of axial length
(AXL), corneal curvature (K) and corneal astigmatism (CA). The accuracies of the
three formulas were analyzed using Bland-Altman analyses and the possible error
sources of each formula were analyzed using multiple regression model. Results:
The majority of patients enrolled had hyperopic shift after cataract surgery. The
mean errors (ME) of the three formulas were SRK/T: 0.70+/-0.89D, Holladay 1:
(1.20+/-0.88) D and Haigis: (0.60+/-0.88) D; the mean absolute errors (MAE) of
the three formulas were (0.81+/-0.79) D, (1.23+/-0.84) D and (0.76+/-0.74) D,
respectively. Both ME and MAE of Holladay formula were significantly greater than
the other two formulas (F=86.31, P<0.01). Besides, the proportion of patients
having a prediction error within 0.50 D was lower in those using Holladay formula
(20.4%, 21/103) than the other two (SRK/T: 38.8%, 40/103, chi(2)=8.41, P<0.01,
Haigis: 45.6%, 47/103, chi(2)=14.84, P<0.01). Bland-Altman analyses showed that
the accuracies of all the three formulas were acceptable in patients of cataract
with high myopia in clinical practice. ME and MAE tended to be larger with longer
axial length, larger corneal curvature and astigmatism of the patients in all
three formulas. However, in eyes with axial length> 30 mm or corneal curvature
<=43.00 D, the MAE of Haigis formula was lower than that of SRK/T formula
(F=63.26,63.94, both P<0.01). The prediction error of SRK/T formula was
positively correlated with axial length and corneal astigmatism (F=33.97, r=0.66,
beta=0.48, P<0.01 and beta=0.42, P<0.01), while for Holladay and Haigis formulas,
in addition to the previous two factors, the errors were also positively
correlated with mean corneal curvature (Holladay 1: F=31.26, r=0.72, AXL:
beta=0.52, P<0.01, K: beta=0.20, P<0.05 and CA: beta=0.37, P<0.01; Haigis:
F=30.96, r=0.72, AXL: beta=0.33, P<0.01, K: beta=0.40, P<0.01 and CA: beta=0.37,
P<0.01). Conclusions: In the selection of IOL formula for high myopic patients
with cataract, Haigis or SRK/T would reduce the prediction error and serve as the
more accurate formulas than Holladay 1. Haigis formula may be more accurate than
SRK/T formula in case of AXL>30 mm or K<=43.00 D. (Chin J Ophthalmol, 2017, 53:
260-265).
PMID- 28412800
TI - [Visual quality comparison after multifocal toric intraocular lens or monofocal
toric intraocular lens implantation].
AB - Objective: To compare visual quality and satisfaction after multifocal toric
intraocular lens (Acrysof IQ Restor toric, ART) and monofocal toric intraocular
lens implantation in patients. Methods: It was a prospective nonrandomized Phase
III clinical trial. Patients with age-related cataract and corneal astigmatism
were enrolled and accepted phacoemulsification combined with implantation of
intraocular lens (IOL) in Henan Provincial Eye Hospital during March 2013 to
December 2014. Fifty-six cases were divided into two groups according to which
IOL they chose. ART group included 28 cases (3l eyes) aged from 41.0 to 72.0
years, with an average age of 61.5 years; toric group included 28 cases (33 eyes)
aged from 42.0 to 75.0 years, with an average age of 63.5 years. Three months
postoperatively, uncorrected distance visual acuity (UDVA) at 5, 70, 40 cm,
corrected distance, intermediate, and near visual acuities, defocus curve,
residual refractive astigmatism, rotational stability of the IOL, contrast
sensitivity and patientsatisfaction were evaluated. All data were processed by
statistic package deal SPSS 16.0. Postoperative visual acuity, residual
astigmatism, IOL axial rotation and contrast sensitivity were compared by
independent samples t test; preoperative and postoperative corneal astigmatism
were compared by paired t-test; spectacle independency and halo incidence were
processed by chi(2) test; visual satisfaction score was analyzed by Mann-Whitney
test. Results: At 3 months postoperatively, in ART group, UDVA was (0.04+/-0.05),
UIVA was (0.24+/-0.15), UNVA was (0.20+/-0.24). While in Toric group, UDVA was
(0.06+/-0.04), UIVA was (0.30+/-0.13), UNVA was (0.47+/-0.21). There was no
significant difference in UDVA between two groups(t=0.79, P=0.433). But in ART
group, UIVA and UNVA were markedly better than those in Toric group(t=2.74,
P=0.008; t=3.45, P<0.01). Depth of focus was 5.50 D (+2.00--3.50 D) in the ART
group and 2.50 D (+1.00--1.50 D) in the Toric group. Average postoperative
residual astigmatism was (-0.45+/-0.41)D in ART group and (-0.41+/-0.32)D in the
Toric group. There was no significant difference between two groups (t=1.05,
P=0.304). Average IOL rotation test was (2.95 degrees +/-1.34 degrees ) in the
ART group and (2.75 degrees +/-1.64 degrees ) in the Toric group. There was no
significant difference between two groups (t=0.67, P=0.452). Spectacle
independency was achieved by 85.7% of patients in the ART group and 32.1% in the
Toric group. There was no signifcant difference in distant visual satisfaction
scores between the two groups(Z=0.71, P>0.05), while the intermediate and near
visual satisfaction scores were significantly different(Z=2.27, P<0.05; Z=2.60,
P<0.05) Conclusions: Both of the ART IOL and toric IOL can correct patients
astigmatism. Implantation of ART IOL in patients with cataract and corneal
astigmatism provided excellent distance, intermediate, and near visual outcomes.
It provided better predictability of the refractive results, nice rotational
stability, and good optical performance. At the same time, it improved the
spectacle independency of cataract patients with astigmatism. (Chin J Ophthalmol,
2017, 53: 274-280).
PMID- 28412801
TI - [Preliminary report on the application of femtosecond laser-assisted anterior
capsulotomy in intumescent white cataract surgery].
AB - Objective: To assess the effect of femtosecond laser-assisted anterior
capsulotomy in intumescent white cataract surgery. Methods: Retrospective case
series study. One hundred and fifty cataract patients (150 eyes) from June 2014
to June 2015 in Wuhan Aier ophthalmology hospital were enrolled in this study.
They were divided into three groups: 50 intumescent white cataract patients (50
eyes) in the study group were performed femtosecond laser-assisted capsulotomy
(LenSx system) operation selectively. Fifty intumescent white cataract patients
(50 eyes) underwent normal manual continuous circular capsulorhexis as the
control group 1. Fifty other types cataract patients (50 eyes) underwent
femtosecond laser-assisted capsulotomy as the control group 2. To observe the
complications such as radial tear in anterior capsule, posterior capsule rupture
and vitreous prolapse occurred during operations in each group respectively. The
microscopic images of the free anterior capsule after dyeing were observed in the
studygroup and the control group 2. Using the German company Oculus Pentacam
three-dimensional anterior eye segment system to collect the Scheimplug images of
each group at 1, 3, 6 months and 1 year after operation. The data were analyzed
by SPSS19.0 software package. Complications during operations in all groups were
compared with Fisher exact test. The eccentricity and tilt of IOL in each group
were analyzed by single factor analysis of variance. The SNK-q test was used to
compare the different follow-up time groups. Results: One hundred and fifty
patients aged from 50 to 86 years old, including 72 male cases and 78 female
cases. In study group, radial tear in anterior capsule occurred in 2 eyes (4%),
adherent tongue-like capsule adhesion was found in 6 eyes (12%), incomplete
capsulotomy button happened in 2 eyes (4%), and posterior capsule rupture and
vitreous prolapse occurred in 1 eye (2%). In the control group 1, radial tear in
anterior capsule occurred in 8 eyes (16%) and posterior capsule rupture and
vitreous prolapse occurred in 3 eyes (6%). The cases number of radial tear in
anterior capsule and posterior capsule rupture and vitreous prolapse in the study
group was obviously lower than the control group 1. The difference was
statistically significant (P<0.05). In the control group 2, all 50 eyes were
successfully completed. The implantation was uneventful and the IOL was centered.
And posterior capsular rupture and vitreous prolapse did not occur. The
difference was statistically significant between the study group and the control
group 2 (P<0.05). After 1 year follow-up, the study group and the control group 2
showed no significant IOL tilt and eccentricity. The eccentricity and tilt of IOL
in horizontal and vertical direction in control group 1 were significantly higher
than those in the study group (F was 2.31, 1.10, 2.78 and 2.90 respectively) and
control group 2 (F was 2.50, 2.32, 2.56 and 2.18respectively). The difference was
statistically significant (P<0.05). Conclusions: Femtosecond laser-assisted
anterior capsulotomy is accurate circle and center to avoid IOL eccentricity and
tilt caused by capsular bag contraction asymmetrically after implantation, so as
to ensure the long-term stability of the visual quality postoperatively. (Chin J
Ophthalmol, 2017, 53: 281-287).
PMID- 28412802
TI - [Analysis of the effect of different surgical methods on the cavernous hemangioma
of the deep orbit].
AB - Objective: To explore the effect of the surgical removal of orbital deep
cavernous hemangioma following the concept of minimal surgical invasion. Methods:
Retrospective case series study. Sixty-three cases with surgical removal of deep
orbital cavernous hemangioma were collected in the Affiliated Eye Hospital of
Nanchang University from May 2012 to August 2015. There were 29 males and 34
females. The age was from 17 to 69 years with mean age (45+/-11) years.The
surgical methods the conjunctival approach orbital surgery, lateral orbital
surgery, medial skin orbital surgery, lateral orbital conjunctiva conjunctival
pathway and endoscopic nasal approach were chosen for different cases. The visual
acuity, visual field and electrophysiological examination were analyzed before
and after operation. Result: Sixty-three patients underwent complete surgically
removal of the tumor. Among them, 32 cases were conducted by conjunctival
approach, 24 cases had improved visual acuity, 5 cases had no change of visual
acuity, 3 cases had decreased visual acuity. Seventeen cases performed with
lateral open orbital surgery had improved visual acuity in 11 cases, no change in
visual acuity in 3 cases and decreased visual acuity in 3 cases postoperatively.
Six cases with approach of the medial orbital surgery had improved visual acuity
in 4 cases, no change of visual acuity in 1 case and decreased visual acuity in 1
case postoperatively. Six cases with approach of outside open orbital surgery
combined with medial conjunctival pathway had improved visual acuity in 4 cases,
no change of visual acuity in 1 case and decreased visual acuity in 1 case
postoperatively. Two cases performed with endoscopic nasal approach. One of them
had normal visual function and no change after surgery. Another had impaired
visual function pre-operatively and it came back to normal postoperatively.
Conclusions: With the concept of minimal surgical invasion, the choice of
appropriate surgical approach can save patients with the greatest degree of
visual function and even improve the visual function of the patients with orbital
cavernous hemangioma. (Chin J Ophthalmol, 2017, 53: 288-293).
PMID- 28412803
TI - [Association analysis between LOXL1 gene and exfoliation syndrome].
AB - Objective: To evaluate the association of LOXL gene and XFS/XFG in Chinese
population. Methods: Experimental research. Fifty unrelated patients from
shenzhen Eye Hospital and Beijing Tongren Hospital with exfoliation syndrome or
exfoliation glaucoma and 100 control subjects were included. All the seven exons
and the splicing region were amplified by polymerase chain reaction (PCR) and
were directly sequenced. The comparison of allelic frequencies and genotype
frequencies between case and control groups was performed using standard chi(2)
test. Result: Allelic association analysis showed that there were significant
differences in the allelic distributions between the two groups for two loci in
the LOXL gene: int6: 25975 C>A and ex7:26145 G>A. The frequency of A allele at
int6: 25975 C>A was significantly higher in cases than in controls (chi(2)=92.31,
P<0.01), OR=1.66(95%CI:1.42-1.96). The frequency of genotype CA was significantly
higher in cases than in controls (chi(2)=109.09, P<0.01), OR=5.00 (95%CI: 2.87
8.70). The frequency of A allele of ex7: 26145 G>A was significantly higher in
cases than in controls (chi(2)=79.25, P<0.01), OR=1.54 (95%CI: 1.33-1.78). The
frequency of genotype GA was significantly higher in cases than in
controls(chi(2)=91.30, P<0.01), OR=3.33 (95%CI: 2.18-5.09). Haplotype AA and AG
were risk and haplotype CG was protective for the disease. Conclusions: Two loci
in the LOXL1 gene were found to be associated with XFS/XFG. Further study is
needed to unravel the effect of LOXL1 on thedevelopment of the disease.(Chin J
Ophthalmol, 2017, 53: 294-299).
PMID- 28412804
TI - [Status and analysis of off-label drug use in department of ophthalmology].
AB - Objective: To investigate and analyze the status of off-label drug use in
department of ophthalmology of Beijing Tongren Hospital. Methods: Cross-sectional
study. Prescription evaluation, off-label drug use application and temporary
medicine purchase application were collected from January 2013 to March 2015. The
off-label use of medication in department of ophthalmology were filtered out and
analyzed according to the category of medications, the category of the off-label
use of medication and the strength of evidence for the off-label use of
medication. Results: Thirty-seven items of off-label uses of medication were
included in this study. The off-label use of medication focused on the
indications (19 items, 51.4%) and route of administration (18 items, 48.6%) in
this study. Nineteen category of medication were involved, which accounted for
1.3% (19/1 462) drugs in the hospital formulary.The top 2 category of medication
were adrenocorticoid drugs (21.1%, 4/19) and antitumor drugs (21.1%, 4/19). There
are evidence to support 37 items of off-label drug uses. 5 items (13.5%) of off
label drug uses were labeled uses approved by Food and Drug Administration. One
item (2.7%) of off-label drug use was in accord with international guidelines.
Twenty items (54.1%) of off-label drug uses were in accord with expert consensus.
Eight off-labels were evaluated by Micromedex, while the other 78.4% (29 items)
were not evaluated by Micromedex. Conclusions: The off-label use of medications
exists widely in department of ophthalmology, having its necessity and
rationality. But we should pay attention to its standard management. (Chin J
Ophthalmol, 2017, 53: 300-304).
PMID- 28412805
TI - [The observation of tacrolimus eye drops preventing the early immunological
rejection after penetrating keratoplasty for fungal keratitis].
AB - Objective: To observe the early immunological rejection prevention effect of
tacrolimus eye drops combined with glucocorticoids on fungal keratitis patients
who received penetrating keratoplasty (PKP). Methods: In a retrospective case
series study, medical records of fungal keratitis patients who received PKP in
Shandong Eye Institute from March 2013 to December 2015 were reviewed. Twenty-six
patients (26 eyes) were given tacrolimus eye drops, and 24 patients (24 eyes)
were given 1% cyclosporine A eye drops immediately after PKP. Two weeks after
PKP, these patients were given low concentration of glucocorticoids if no fungal
recurrence was found. Immune rejection, fungal recurrence, intraocular pressure,
and drug irritation symptoms were monitored. Data were analyzed by chi-square
test and independent t-test. Results: The average follow-up was 7 months (range,
3 to 12 months) postoperatively. The rejection rate was 15.3% in the tacrolimus
group and 47.8% in the cyclosporine A group (chi(2)=5.510, P<0.05). One patient
in the tacrolimus group and two patients in the cyclosporine A group suffered
fungal recurrence. Two patients in the tacrolimus group and four patients in the
cyclosporine A group had secondary glaucoma. The intraocular pressure was
controlled. Three patients receiving tacrolimus eye drops and 13 patients
receiving cyclosporine A eye drops had mild irritation symptoms. Conclusions:
Tacrolimus eye drops combined with low concentration of glucocorticoids can
prevent the early immunological rejection after PKP for fungalkeratitis
effectively and safely. (Chin J Ophthalmol, 2017, 53:305-310).
PMID- 28412806
TI - [Correlation between Alzheimer disease and cataract].
AB - Alzheimer disease (AD) is a progressive neurodegenerative disease and is a
leading cause of dementia among elders. In the early phase of AD, even if
neuropathological changes presented, but little to none clinical symptoms were
found. Therefore, it is difficult to diagnose AD in the beginning of the disease.
It is vital to find a noninvasive way for both diagnose and prognosis of AD.
Studies have found that beta-amyloid (Abeta) works as a connection between AD and
cataract. This review will discuss AD and its associated markers which may be
present in the lens and cataract related AD to provide more basis for early
diagnosis of AD. (Chin J Ophthalmol, 2017, 53: 314-316).
PMID- 28412807
TI - [Clinical features, risk factors and progresses on treatment of recurrent Vogt
Koyanagi-Harada disease].
AB - Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis
associated with central nervous system, auditory, and integumentary
manifestations. Clinically, VKH usually responds well to early aggressive
glucocorticosteroid treatment and may be cured without any clinically significant
sequelae. Some patients, however, may enter the chronic recurrent phase, which
may result in marked loss of vision due to complications such as complicated
cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly
characterized by anterior uveitis associated with thickening of the choroid.
Initial poor visual acuity, severe anterior chamber reaction, choroidal
folds,rapid tapering of systemic corticosteroids or inadequate duration of
treatment, and development of extraocular manifestations may be risk factors of
disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as
effective strategy for recurrence of VKH. The positive effects of other
immunosuppressive agents and biologic agents on treatment of chronic recurrent
and refractory VKH have been gradually recognized by the uveitis community. (Chin
J Ophthalmol, 2017, 53: 317-320).
PMID- 28412808
TI - Spontaneously Assembled Nano-aggregates in Clear Green Tea Infusions from
Camellia ptilophylla and Camellia sinensis.
AB - Tea nano-aggregates spontaneously assembled in clear tea infusions are considered
as the precursors of tea cream, although their molecular basis remains obscure.
Here, we characterized nano-aggregates in green tea infusions from Camellia
ptilophylla, a peculiar tea variety with 6.0% of theobromine, and Camellia
sinensis as the control for comparative purpose. Numerous negatively charged
spherical colloidal particles of 50-100 nm in diameter were primarily found in
both green tea infusions. Catechins, proteins, and carbohydrates were confirmed
as the dominant components in green tea nano-aggregates. In addition, iron,
copper, nickel, proteins, and gallated catechins exhibited higher aggregating
affinity than other components, whereas methylxanthines and calcium contributed
to the transformation of nano-aggregates into tea cream. Green tea nano
aggregates were partly destroyed by simulated gastrointestinal digestion, and
removing theses peculiar particles dramatically attenuated the bioaccessibility
of methylxanthines, theanine, and some catechin monomers in green tea infusions.
This study enhanced our knowledge of molecular interactions in the formation of
green tea cream and provided insight into physicochemical profiles, phytochemical
nature, and functional effects of green tea nano-aggregates.
PMID- 28412809
TI - Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid,
a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast
Cells, and Rat Uterine Tissues.
AB - Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit
diverse estrogenic activities. In this study we investigated the estrogenic
activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy
1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound
elicited different transcriptional activities of estrogen agonist at low
concentrations (0.1-1 MUM) and antagonist at high concentrations (10-50 MUM)
using luciferase reporter gene assay in HEK-293T cells. In human breast cancer
(MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating
ERalpha-signaling and suppressing estrogen-responsive genes, whereas it
attenuated the uterotrophic effect of estrogen in immature ovariectomized rats.
Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell
differentiation and the related bone markers, indicating its positive osteogenic
effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist
of catechol diarylheptanoid from C. comosa, which is scientific evidence
supporting its potential as a dietary supplement to prevent bone loss with low
risk of breast and uterine cancers in postmenopausal women.
PMID- 28412810
TI - Ultraviolet Light Makes dGMP Floppy: Femtosecond Stimulated Raman Spectroscopy of
2'-Deoxyguanosine 5'-Monophosphate.
AB - The ultrafast dynamics of 2'-deoxyguanosine 5'-monophosphate after excitation
with ultraviolet light has been studied with femtosecond transient absorption
(TA) and femtosecond stimulated Raman spectroscopy (FSRS). TA kinetics and
transient anisotropy spectra reveal a rapid relaxation from the Franck-Condon
region, producing an extremely red-shifted stimulated emission band at ~440 nm
that is formed after 200 fs and subsequent relaxation for 0.8-1.5 ps, consistent
with prior studies. Viscosity dependence shows that the initial relaxation,
before 0.5 ps, is the same in water or viscous glycerol/water mixtures, but after
0.5 ps the dynamics significantly slow down in a viscous solution. This indicates
that large amplitude structural changes occur after 0.5 ps following
photoexcitation. FSRS obtained with both 480 and 600 nm Raman pump pulses observe
very broad Raman peaks at 509 and 1530 cm-1, as well as a narrower peak at 1179
cm-1. All of the Raman peaks decay with 0.7-1.3 ps time constants. The 1530 cm-1
peak also shows an increasing inhomogeneous linewidth over the first 0.3 ps. Our
TA and FSRS data are consistent with a structurally inhomogeneous population in
the S1 (La) state and, in particular, with previous theoretical models in which
out-of-plane distortion at C2 and the amine move the molecule toward a conical
intersection with the ground state. These FSRS data are the first to directly
observe the structural inhomogeneity imparted upon the excited-state population
by the broad, flat potential energy surface of the S1 (La) state.
PMID- 28412811
TI - Two-Dimensional Metal-Free Organic Multiferroic Material for Design of
Multifunctional Integrated Circuits.
AB - Coexistence of ferromagnetism and ferroelectricity in a single 2D material is
highly desirable for integration of multifunctional units in 2D material-based
circuits. We report theoretical evidence of C6N8H organic network as being the
first 2D organic multiferroic material with coexisting ferromagnetic and
ferroelectric properties. The ferroelectricity stems from multimode proton
transfer within the 2D C6N8H network, in which a long-range proton-transfer mode
is enabled by the facilitation of oxygen molecule when the network is exposed to
the air. Such oxygen-assisted ferroelectricity also leads to a high Curie
temperature and coupling between ferroelectricity and ferromagnetism. We also
find that hydrogenation and carbon doping can transform the 2D g-C3N4 network
from an insulator to an n-type/p-type magnetic semiconductor with modest bandgap.
Akin to the dopant induced n/p channels in silicon wafer, a variety of dopant
created functional units can be integrated into the g-C3N4 wafer by design for
nanoelectronic applications.
PMID- 28412813
TI - Singlet Oxygen Detection on a Nanostructured Porous Silicon Thin Film via
Photonic Luminescence Enhancements.
AB - Because reactive oxygen species are involved in a range of pathologies,
developing analytical tools for this group of molecules opens new vistas for
biomedical diagnostics. Herein, we fabricate a porous silicon microcavity (pSiMC)
functionalized with luminescent singlet oxygen (1O2) probe EuA ((Eu(III)-2,2',2"
(10-(2-((4-(2-((4-(2-((anthracen-9-ylmethyl)amino)ethyl)-1H-1,2,3-triazol-1
yl)amino)-2-oxoethyl)-2-oxo-1,2-dihydroquinolin-7-yl)amino)-2-oxoethyl)-1,4,7,10
tetraazacyclododecane-1,4,7-triyl)triacetic acid) as proof of concept of an
optical sensor for reactive oxygen species. We characterize each surface
modification step of the pSiMC by means of FTIR and X-ray photoelectron
spectroscopy as well as by determining the optical shifts of the resonance
wavelength of the pSiMC. The luminescence signal upon detection of 1O2 on the EuA
modified pSiMC is enhanced ~2-fold compared to that of a single layer and a
detuned microcavity. The sensing performance of the EuA probe is improved
significantly on the pSiMC compared to that in aqueous solution, giving a limit
of 1O2 detection of 3.7 * 10-8 M.
PMID- 28412812
TI - An IonStar Experimental Strategy for MS1 Ion Current-Based Quantification Using
Ultrahigh-Field Orbitrap: Reproducible, In-Depth, and Accurate Protein
Measurement in Large Cohorts.
AB - In-depth and reproducible protein measurement in many biological samples is often
critical for pharmaceutical/biomedical proteomics but remains challenging. MS1
based quantification using quadrupole/ultrahigh-field Orbitrap (Q/UHF-Orbitrap)
holds great promise, but the critically important experimental approaches
enabling reliable large-cohort analysis have long been overlooked. Here we
described an IonStar experimental strategy achieving excellent quantitative
quality of MS1 quantification. Key features include: (i) an optimized, surfactant
aided sample preparation approach provides highly efficient (>75% recovery) and
reproducible (<15% CV) peptide recovery across large cell/tissue cohorts; (ii) a
long column with modest gradient length (2.5 h) yields the optimal balance of
depth/throughput on a Q/UHF-Orbitrap; (iii) a large-ID trap not only enables
highly reproducible gradient delivery as for the first time observed via real
time conductivity monitoring, but also increases quantitative loading capacity by
>8-fold and quantified >25% more proteins; (iv) an optimized HCD-OT markedly
outperforms HCD-IT when analyzing large cohorts with high loading amounts; (v)
selective removal of hydrophobic/hydrophilic matrix components using a novel
selective trapping/delivery approach enables reproducible, robust LC-MS analysis
of >100 biological samples in a single set, eliminating batch effect; (vi) MS1
acquired at higher resolution (fwhm = 120 k) provides enhanced S/N and
quantitative accuracy/precision for low-abundance species. We examined this
pipeline by analyzing a 5 group, 20 samples biological benchmark sample set, and
quantified 6273 unique proteins (>=2 peptides/protein) under stringent cutoffs
without fractionation, 6234 (>99.4%) without missing data in any of the 20
samples. The strategy achieved high quantitative accuracy (3-6% media error), low
intragroup variation (6-9% media intragroup CV) and low false-positive biomarker
discovery rates (3-8%) across the five groups, with quantified protein abundances
spanning >6.5 orders of magnitude. Finally, this strategy is straightforward,
robust, and broadly applicable in pharmaceutical/biomedical investigations.
PMID- 28412814
TI - Fe3O4@PANI Hybrid Shell as a Multifunctional Support for Au Nanocatalysts with a
Remarkably Improved Catalytic Performance.
AB - Au@Fe3O4@PANI hybrid shells with controllable polyaniline (PANI) coatings as
advanced supported catalysts have been fabricated. Specifically, Fe3O4 and Au
nanoparticles were assembled on SiO2 templates, followed by conducting polymer
PANI coating, leading to the formation of Au@Fe3O4@PANI hybrid shells after the
template removal. The resultant supported Au nanocatalysts not only maintain
hollow structures but also possess high saturation magnetization (65.46 emu/g).
Catalytic tests toward the reduction of 4-nitrophenol in the presence of NaBH4
indicate that PANI and Fe3O4 not only endow high stability and recyclability but
also can largely improve the catalytic activity of Au nanoparticles because of
their synergetic effects. It is believed that Fe3O4@PANI hybrid shells can be
regarded as multifunctional supports for noble metal nanocatalysts with a
remarkably improved catalytic performance.
PMID- 28412816
TI - Metal-Free Electrophilic Phosphination/Cyclization of Alkynes.
AB - A metal-free electrophilic phosphination reaction has been developed.
Electrophilic phosphorus species generated in situ from secondary phosphine
oxides and Tf2O smoothly couple with alkynes possessing pendant nucleophiles to
afford the corresponding phosphinated cyclization products in good yield.
Preliminary NMR studies show that phosphirenium species may be involved as
intermediates of the cyclization reactions.
PMID- 28412815
TI - High-Throughput Analysis of Intact Human Proteins Using UVPD and HCD on an
Orbitrap Mass Spectrometer.
AB - The analysis of intact proteins (top-down strategy) by mass spectrometry has
great potential to elucidate proteoform variation, including patterns of post
translational modifications (PTMs), which may not be discernible by analysis of
peptides alone (bottom-up approach). To maximize sequence coverage and
localization of PTMs, various fragmentation modes have been developed to produce
fragment ions from deep within intact proteins. Ultraviolet photodissociation
(UVPD) has recently been shown to produce high sequence coverage and PTM
retention on a variety of proteins, with increasing evidence of efficacy on a
chromatographic time scale. However, utilization of UVPD for high-throughput top
down analysis to date has been limited by bioinformatics. Here we detected 153
proteins and 489 proteoforms using UVPD and 271 proteins and 982 proteoforms
using higher energy collisional dissociation (HCD) in a comparative analysis of
HeLa whole-cell lysate by qualitative top-down proteomics. Of the total detected
proteoforms, 286 overlapped between the UVPD and HCD data sets, with 68% of
proteoforms having C scores greater than 40 for UVPD and 63% for HCD. The average
sequence coverage (28 +/- 20% for UVPD versus 17 +/- 8% for HCD, p < 0.0001) was
found to be higher for UVPD than HCD and with a trend toward improvement in q
value for the UVPD data set. This study demonstrates the complementarity of UVPD
and HCD for more extensive protein profiling and proteoform characterization.
PMID- 28412817
TI - Impact of Microcystis aeruginosa Exudate on the Formation and Reactivity of Iron
Oxide Particles Following Fe(II) and Fe(III) Addition.
AB - Impact of the organic exudate secreted by a toxic strain of Microcystis
aeruginosa on the formation, aggregation, and reactivity of iron oxides that are
formed on addition of Fe(II) and Fe(III) salts to a solution of the exudate is
investigated in this study. The exudate has a stabilizing effect on the particles
formed with decreased aggregation rate and increased critical coagulant
concentration required for diffusion-limited aggregation to occur. These results
suggest that the presence of algal exudates from Microcystis aeruginosa may
significantly influence particle aggregation both in natural water bodies where
Fe(II) oxidation results in oxide formation and in water treatment where Fe(III)
salts are commonly added to aid particle growth and contaminant capture. The
exudate also affects the reactivity of iron oxide particles formed with exudate
coated particles undergoing faster dissolution than bare iron oxide particles.
This has implications to iron availability, especially where algae procure iron
via dissolution of iron oxide particles as a result of either reaction with
reducing moieties, light-mediated ligand to metal charge transfer and/or reaction
with siderophores. The increased reactivity of exudate coated particles is
attributed, for the most part, to the smaller size of these particles, higher
surface area and increased accessibility of surface sites.
PMID- 28412818
TI - Transparent Ethenylene-Bridged Polymethylsiloxane Aerogels: Mechanical
Flexibility and Strength and Availability for Addition Reaction.
AB - Transparent, low-density ethenylene-bridged polymethylsiloxane [Ethe-BPMS,
O2/2(CH3)Si-CH?CH-Si(CH3)O2/2] aerogels from 1,2-bis(methyldiethoxysilyl)ethene
have successfully been synthesized via a sol-gel process. A two-step sol-gel
process composed of hydrolysis under acidic conditions and polycondensation under
basic conditions in a liquid surfactant produces a homogeneous pore structure
based on cross-linked nanosized colloidal particles. Visible-light transmittance
of the aerogels varies with the concentration of the base catalyst and reaches as
high as 87% (at a wavelength of 550 nm for a 10 mm thick sample). Gelation and
aging temperature strongly affect the deformation behavior of the resultant
aerogels against uniaxial compression, and the obtained aerogels prepared at 80
degrees C show high elasticity after being unloaded. This highly resilient
behavior is primarily derived from the rigidity of ethenylene groups, which is
confirmed by a comparison with other aerogels with similar molecular structures,
ethylene-bridged polymethylsiloxane and polymethylsilsesquioxane. Applicability
of the addition reaction using a Diels-Alder reaction of benzocyclobutene has
also been investigated, revealing that a successful addition takes place on the
ethenylene linkings, which is verified using Raman and solid-state NMR
spectroscopies. Insights into the effect of molecular structure on mechanical
properties and the availability of surface functionalization provided in this
study are important for realizing transparent aerogels with the desired
functionality.
PMID- 28412819
TI - Structural and Spectroscopic Characterization of TPGS Micelles: Disruptive Role
of Cyclodextrins and Kinetic Pathways.
AB - The aggregation and structure of d-alpha-tocopheryl polyethylene glycol succinate
micelles, TPGS-1000, an amphiphilic derivative of vitamin E, were characterized
using scattering and spectroscopic methods, and the impact of different
cyclodextrins (CDs) on the self-assembly was investigated, with the view of
combining these two versatile pharmaceutical excipients in drug formulations.
Combined small-angle neutron scattering (SANS), dynamic light scattering, and
time-resolved and steady-state fluorescence emission experiments revealed a core
shell architecture with a high aggregation number (Nagg ~ 100) and a highly
hydrated poly(ethylene oxide) corona (~11 molecules of solvent per ethylene oxide
unit). Micelles form gradually, with no sharp onset. Structural parameters and
hydration of the aggregates were surprisingly stable with both temperature and
concentration, which is a critical advantage for their use in pharmaceutical
formulations. CDs were shown to affect the self-assembly of TPGS in different
ways. Whereas native CDs induced the precipitation of a solid complex
(pseudopolyrotaxane), methylated beta-CDs led to different outcomes: constructive
(micellar expansion), destructive (micellar rupture), or no effect, depending on
the number of substituents and whether the substitution pattern was regular or
random on the rims of the macrocycle. Time-resolved SANS studies on mixtures of
TPGS with regularly dimethylated beta-CD (DIMEB), which ruptures the micelles,
revealed an almost instantaneous demicellization (<100 ms) and showed that the
process involved the formation of large aggregates whose size evolved over time.
Micellar rupture is caused by the formation of a TPGS-DIMEB inclusion complex,
involving the incorporation of up to three macrocycles on the tocopherol, as
shown by proton nuclear magnetic resonance (NMR) and ROESY NMR. Analysis of NMR
data using Hill's equation revealed that the binding is rather cooperative, with
the threading of the CD favoring the subsequent inclusion of additional CDs on
the aliphatic moiety.
PMID- 28412820
TI - Systems Toxicology II: A Special Issue.
PMID- 28412822
TI - Determinants of Lifestyle Behavior in Iranian Adults with Prediabetes: Applying
the Theory of Planned Behavior.
AB - OBJECTIVE: Prediabetic condition can lead to development of type 2 diabetes,
especially in individuals who do not adhere to a healthy lifestyle. The aim of
the present study was to investigate the socio-cognitive factors using the Theory
of Planned Behavior (TPB) that may be associated with the choice of lifestyle in
prediabetic patients. METHODS: A prospective study with one-month follow up was
designed to collect data from 350 individuals with prediabetic conditions. A
questionnaire was used to collect the information, including demographic
variables, exercise behavior, food consumption, as well as the constructs of the
TPB (attitude, subjective norms, perceived behavioral control, and behavioral
intention) regarding physical activity and dietary choice. The correlations
between TPB variables and the dependent variables (dietary choice, physical
activity) were assessed using Spearman correlation and multiple regression
models. RESULT: In total, 303 people participated. The mean age of the
participants was 53.0 (SD 11.5) years and 42% were males. Significant
correlations were found between all TPB constructs and both dependent variables
(healthy eating and exercise behaviors) both at baseline and after one month (P <
0.01). The predictive validity of the TPB over time was proved for both dependent
variables where past and future behaviors were significantly correlated with the
constructs. Nearly 87% of the variance in exercise behavior and 72% of the
variance in healthy eating behavior were explainable by TPB constructs.
CONCLUSION: The TPB may be a useful model to predict behaviors of physical
activity and dietary choice among prediabetic people. Therefore, it may be used
to monitor lifestyle modification to prevent development of diabetes among people
with prediabetic conditions.
PMID- 28412823
TI - Epidemiologic Study of Opium Use in Pars Cohort Study: A Study of 9000 Adults in
a Rural Southern Area of Iran.
AB - BACKGROUND: Opium is one of the most common substances used worldwide with
variable epidemiologic features in different regions. This study was performed in
southern Iran, to find the epidemiology of opium use and its association with
different factors and diseases. METHODS: This cross-sectional study was performed
on baseline data extracted from Pars Cohort Study performed in Valashahr, a rural
area in southern Iran. For any subject, information was collected about
demographic factors, some common diseases including heart disease, stroke and
hypertension and the state of using opium, other substances and cigarettes.
RESULTS: There were 4276 males and 4988 females, with a mean age of 52.6 +/- 9.7
years of whom 8.4% reported opium use (17.3% of males and 0.7% of females). In
men, the history of stroke and heart disease were significantly more common in
opium users (12.6% vs. 8.8%, P = 0.001 and 2.8% vs. 1.5%, P = 0.01, respectively)
while the history of hypertension was significantly more common in non-opium
users (7.8% vs. 10.3%, P = 0.04). Younger age, male gender, being non-married and
positive history of joint pain, cigarette smoking and alcohol consumption were
the factors associated with opium use. CONCLUSION: Opium use is common in non
married men who have a positive history of cigarette smoking and alcohol
consumption in the rural population of southern Iran. It is associated with
increased risk of heart disease and stroke and decreased risk of hypertension in
males. Global interventional and preventive measures are required to control this
complicated social problem.
PMID- 28412824
TI - Assessment of Lean Patients with Non-alcoholic Fatty Liver Disease in a Middle
Income Country; Prevalence and Its Association with Metabolic Disorders: A Cross
sectional Study.
AB - BACKGROUND: Recent data has proven that the WHO (world health organization) cut
off for obesity is not applicable to the Asian population. This study aims to
estimate the prevalence of lean NAFLD (non-alcoholic fatty liver disease) in the
capital of Iran and extract probable predictors for this growing health issue in
this population. METHODS: This is a population-based cross-sectional study on
apparently healthy subjects over 18 years of age. The participants were
interviewed for baseline demographic and clinical information. They were
subsequently referred for physical examination and blood sampling. NAFLD was
diagnosed using abdominal ultrasonography by a single expert radiologist.
RESULTS: Of 927 eligible participants who entered the study, 314 were lean; BMI
(body mass index) <25 kg/m2. The prevalence of NAFLD was 17.52% (95% Exact CI:
13.48%-22.18%). BMI, SBP (systolic blood pressure), DBP (diastolic blood
pressure), total cholesterol, HDL (high-density lipoprotein), LDL (low-density
lipoprotein) and triglyceride were significantly different in patients with
NAFLD. In the final multiple analysis, higher levels of triglyceride, upper SBP
and higher BMI even in the range of less than 25 kg/m2 were independent
predictors of NAFLD in lean participants. In lean participants with more
components of metabolic syndrome, the prevalence of NAFLD increased significantly
(all P < 0.01). BMI cut-offs in men and women along with waist circumference cut
off in men could significantly predict the presence of NAFLD in lean patients.
After comparing these values, McNemar test showed that BMI cut-offs are more
robust than waist circumference cut-offs for predicting the presence of NAFLD in
lean subjects (P < 0.01). CONCLUSION: The prevalence of NAFLD in lean subjects in
a sample of Iranian population is 17.52%. Hypertriglyceridemia, higher SBP, and
higher BMI especially over 23.2 are independent factors associated with the
presence of NAFLD in lean subjects.
PMID- 28412825
TI - Family Dinner Frequency is Inversely Related to Mental Disorders and Obesity in
Adolescents: the CASPIAN-III Study.
AB - PURPOSE: Family dinner is a proxy of family connectedness that may affect mental
health. The present study aimed to examine the associations of frequency of
family dinner with mental disorders and obesity in a nationally-representative
sample of Iranian adolescents. METHODS: A total of 5528 Iranians adolescents aged
10-18 years were enrolled in 2009-2010 in the third survey of a national
surveillance program, entitled Childhood and Adolescence Surveillance and
Prevention of Adult Non-communicable disease (CASPIAN-III) study. The frequency
of family dinner meal was assessed. Mental health assessments were done as part
of the World Health Organization-Global School-based Student Health Survey. The
odds of having mental disorders and obesity were assessed by logistic regression.
RESULTS: No significant difference was found in dietary intake between family
dinner consumers (>=5 times (night)/wk) and skippers (<5 times/wk); however, they
were more likely to consume breakfast and had higher meal frequency. After
controlling for some confounders, dinner consumers had lower odds for all types
of mental disorders (OR = 0.55; 95% CI = 0.47-0.64), anxiety (OR = 0.47; 95% CI =
0.4-0.54), insomnia (OR = 0.6; 95% CI = 0.53-0.7), and confusion (OR = 0.7; 95%
CI = 0.6-0.86), as well as the body mass index- z score (OR = 0.78; 95% CI = 0.73
0.84). CONCLUSION: The current study showed an inverse relationship between the
frequency of family dinner consuming and mental disorders and obesity in a
nationally-representative sample of Iranian adolescents. Such simple
recommendations for consuming family dinner for families may be feasible,
sustainable, and effective for health promotion and disease prevention.
PMID- 28412826
TI - Prevalence of Human T-lymphotropic virus type 1 (HTLV-1) Infection in Patients
with Hematologic Disorders and Non-Hematologic Malignancies in a Tertiary
Referral Hospital.
AB - BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus
identified in human. The current evidence is quite scarce regarding the potential
role of HTLV-1 in pathogenesis of hematologic disorders and non-hematologic
malignancies. OBJECTIVES: The aim of this study is to evaluate the prevalence of
HTLV-1 infection in patients with hematologic disorders and non-hematologic
malignancies. METHODS: This cross-sectional study was conducted on 505 cases of
definite diagnosis of hematologic disorders including malignancies as well as non
malignant disorders such as polycythemia and myelofibrosis and non-hematologic
malignancies referred to the hematology and medical oncology ward at Army
Hospital 501 from January 2015 to January 2016. A 3-mL blood specimen was
collected from each patient and tested for the presence of anti-HTLV-1 antibodies
using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS
software package version 19 (IBM, New York, USA). Data are presented as mean +/-
SD if normally distributed and otherwise as median (range). RESULTS: Totally, 242
(48%) males and 263 (52%) females with a mean +/- SD age of 52.09 +/- 16.24 were
enrolled in this study. In total, there were 9 (1.78%) cases positive for HTLV-1
infection including 4 males and 5 females. Seven out of 287 (2.4%) patients with
hematologic disorders were infected by HTLV-1. In non-hematologic malignancies, 2
out of 211 cases were positive (0.9%). There was no HTLV-1 positive case in 7
patients with both hematologic and non-hematologic disorders. The difference in
HTLV-1 infection prevalence between patients with hematologic disorders and non
hematologic malignancies was not statistically significant different (P = 0.31).
There was no association between sex and transfusion history with HTLV-1
infection in this population (P = 0.9 and 0.7, respectively). CONCLUSIONS: Our
study revealed that the prevalence of HTLV-1 in hematologic disorders is higher
than the general population. Further larger prospective studies are recommended
to corroborate the current evidence.
PMID- 28412827
TI - Challenges of Tobacco Control Program in Iran.
AB - BACKGROUND: This study assessed the status of cigarette marketing in Iran as well
as the attitude of smokers toward smoking and the policies and tobacco control
programs in the country. METHODS: This cross-sectional study was conducted on
3480 volunteer smokers in six provinces, using a stratified cluster random
sampling method. The study population consisted of smokers who used at least one
cigarette per day. The data collection tool was an anonymous self-administered
questionnaire including basic information and 20 five-choice questions related to
participants' attitude toward smoking habits (Cronbach's alpha; 79.73%.).
RESULTS: The majority (66.9%) of participants started smoking at the age of 10 to
19 years and 61.1% used foreign cigarettes. Of 160 marketed brands, 38 (23.8%)
were domestic and 122 (76.2%) were foreign, including 63 (39.3%) imported and 59
(36.9%) smuggled brands. Being tempted (25.0%), getting nervous (24.1%), and
seeking euphoria (24.1%) were the most common reasons for restarting cigarette
smoking after cessation. The majority of participants believed that smoking in
public places was a violation of the rights of others and smoking should be
avoided in such places. CONCLUSION: Smoking prevention programs should focus on
adolescents as the most vulnerable age group. Raising the retail price of tobacco
products through increasing taxes can reduce consumption, particularly among
first starters and youth. However, increasing taxes and prices of tobacco
products may be effective when simultaneous effective measures are implemented to
eliminate all kinds of illicit trade in all forms of tobacco products.
PMID- 28412828
TI - Magnetic Resonance Angiographic Study of Anatomic Variations of the Circle of
Willis in a Population in Tehran.
AB - BACKGROUND AND OBJECTIVES: The circle of Willis, an anastomotic polygon at the
base of the brain, forms an important collateral network to maintain cerebral
blood perfusion. The aim of this study was to investigate different anatomic
variations of the circle of Willis and their prevalence. METHODS: This cross
sectional study was conducted on 525 healthy participants including 205 men and
320 women. The mean age of the patients was 51.5 years. Three-dimensional time-of
flight magnetic resonance angiography (3D-TOF MRA) technique was used. Vascular
variations in the anterior and posterior parts of the circle were evaluated.
RESULTS: The findings show that the complete circle of Willis was visible in a
small number of patients. The circle of Willis had a complete vascular structure
in 20.9% of the patients. The anterior part of the circle of Willis had a
complete structure in 80.95% of the cases, while the posterior part had a
complete structure in 20.95% of the cases. CONCLUSION: We observed wide
variations in the circle of Willis configuration in our study. Similar to other
studies, most variations are related to the posterior part of the circle of
Willis. Absence of bilateral posterior communicating artery variation is more
common than other types of variations in this population.
PMID- 28412829
TI - EGFR Expression in Patients with Esophageal Squamous Cell Carcinoma and its
Association with Pathologic Response to Preoperative Chemoradiotherapy: A Study
in Northeastern Iran.
AB - INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all
esophageal cancers worldwide. It is the most common histological type of
esophageal carcinoma in low-resource countries. ESCC is prevalent in Asian
countries, accounting for more than 95% of esophageal cancers. The epidermal
growth factor receptor (EGFR) is involved in cancer development, as its gene is
often mutated and/or amplified in cancer cells. According to recent statistics,
esophageal cancer is the eighth most common cancer in Iran. METHODS: In this
retrospective study, we assessed EGFR overexpression, using immunohistochemistry
(IHC) in 68 patients with ESCC, undergoing neoadjuvant chemoradiotherapy and
esophagectomy in 2011-2014. The treatment protocol included external beam
radiotherapy (40 Gy), concomitant with cisplatin 20mg/m2 and 5- fluorouracil (5
FU) 1000 mg/m2 for 4 consecutive days during the first and fourth weeks of
treatment. To compare the two groups (EGFR positive and negative) in terms of
complete pathologic response, Chi-square test was performed using SPSS version
16. RESULTS: The median age of the patients was 59 years (range: 27-70 years),
with a female-to-male ratio of 1.06. Overall, 70% of the subjects showed EGFR
overexpression. Complete pathologic response to neoadjuvant treatment was
significantly higher in EGFR-positive patients (40% vs. 15.8%, P = 0.05). In all
cases, 1- and 3-year overall survival rates were 86.6% +/- 4.1 and 48% +/- 6.9,
respectively. The 1- and 3-year disease free survival rates were calculated as
71.8% +/- 5.4 and 44.3% +/- 6.5, respectively. The overall survival rate was
relatively higher in cases with EGFR overexpression, although the difference was
not statistically significant (5-year survival rate: 47.9 +/- 8.2 vs. 30.9 +/-
13, P = 0.23). CONCLUSION: EGFR overexpression was reported in the majority of
patients with ESCC in northeastern Iran. Moreover, EGFR overexpression was
significantly associated with complete pathologic response.
PMID- 28412830
TI - Expression and Immunogenicity of VP40 Protein of ZEBOV.
AB - BACKGROUND: EBOV outbreaks continue to threaten the world due to the absence of
effective vaccines and therapeutics. Easy-to-use and rapid diagnostic tests for
EBOV are highly desired for prevention and control of the EVD epidemic. METHODS:
Escherichia coli expression system was used to express VP40 protein of Zaire
Ebola virus (ZEBOV) as water-soluble protein upon optimization of temperature,
time, and IPTG concentration. VP40 protein was purified through Ni-NTA affinity
chromatography and applied to immunize rabbits for immunogenicity analysis.
Rabbit polyclonal antibodies against VP40 protein was produced and antibody
response was analyzed using Western blot, enzyme-linked immunosorbent assay
(ELISA), and immunoperoxidase monolayer assay (IPMA). RESULTS: Recombinant full
length VP40 protein of ZEBOV was expressed in E. coli Rosetta (DE3) cells as
water-soluble protein. Analysis of antibody responses showed that rabbit
polyclonal antibodies against VP40 protein could react specifically with this E.
coli-expressed protein in Western blot and ELISA, and antibody titers in ELISA
reached 1:25600. Besides, the produced rabbit polyclonal antibodies bound to VP40
proteins eukaryotically expressed by transfecting pcDNA-eGFP-VP40 into BHK-21
cells in IPMA. CONCLUSION: These results show that the prokaryotically expressed
VP40 protein has high immunogenicity and can be used as diagnostic antigen in
ELISA and other immunoassays. The strategy used in this study might be a
potential way for preparing diagnostic agents for prevention and control of
exotic diseases.
PMID- 28412831
TI - Unfair Judgment against Iranian Scientists.
PMID- 28412832
TI - Gondeshapur Revisited; What Historical Evidence?
AB - In recent years, in European academic circles, there has been a trend to dismiss
Gondeshapur as a myth perpetrated by the Bokhtishu family in early Islamic era,
despite many historiographical attestations. The writings of Islamic historians
such as Al-Qifti and Ibn Abi Usaibia have been discounted as exaggerations by non
contemporary historians, and the lack of primary Pahlavi sources blamed for
historical hyperbole. In this essay, I have attempted to show through primary
Syriac Christian texts, that there was both a medical school and a bimarestan in
Gondeshapur in pre-Islamic Sassanid era, and that Galenic medical texts had been
translated and taught in that institution.
PMID- 28412833
TI - Medical Concepts in Ferdowsi's Shahnameh.
PMID- 28412835
TI - Validation of a Seven-Factor Structure for the Motives for Playing Drinking Games
Measure.
AB - Playing drinking games can be characterized as a high-risk drinking activity
because games are typically designed to promote heavy alcohol consumption. While
research suggests that young adults are motivated to play drinking games for a
variety of reasons (e.g., for thrills/fun, for the competition), the Motives for
Playing Drinking Games measure has received limited empirical attention. We
examined the psychometric properties of this measure with a confirmation sample
of young adults recruited from Amazon's MTurk ( N = 1,809, ages 18-25 years, 47%
men; 41% not currently enrolled in college) and a validation sample of college
students ( N = 671; ages 18-23 years; 26% men). Contrary to the 8-factor model
obtained by Johnson and Sheets in a study published in 2004, examination of the
factor structure with our confirmation sample yielded a revised 7-factor model
that was invariant across race/ethnicity and college student status. This model
was also validated with the college student sample. In the confirmation sample,
enhancement/thrills and sexual pursuit motives for playing drinking games were
positively associated with gaming frequency/consumption and negative gaming
consequences. Furthermore, conformity motives for playing drinking games were
positively associated with negative gaming consequences, while competition
motives were positively associated with gaming frequency. These findings have
significant implications for research and prevention/intervention efforts.
PMID- 28412836
TI - Reducing Time to Internal Medicine Consultation in the ED of a Community-Based
Hospital: A Commentary on a Quality Improvement Initiative.
PMID- 28412837
TI - Reliability and Validity of START and LSI-R Assessments in Mental Health Jail
Diversion Clients.
AB - Risk assessment instruments are increasingly used in mental health jail diversion
programs. This study examined the reliability and validity of Short-Term
Assessment of Risk and Treatability (START) and Level of Service Inventory
Revised (LSI-R) assessments overall and by client race. Research assistants
completed START and LSI-R assessments for 95 diversion clients. Arrests and jail
days were collected via official records and self-report 3, 6, 9, 12, and 18
months after baseline. Assessments demonstrated good interrater reliability and
convergent validity. START strength total scores and LSI-R risk estimates were
the strongest predictors of recidivism. Total scores and risk estimates did not
differ as a function of client race, but there were some differences in accuracy
of START vulnerability and LSI-R total scores and risk estimates in predicting
jail days (but not arrests), over shorter follow-ups. No such differences were
found for START strength total scores across any follow-up period or recidivism
measure.
PMID- 28412838
TI - Self-reported sleep complaints are associated with adverse health outcomes: cross
sectional analysis of the 2002/03 New Zealand Health Survey.
AB - OBJECTIVE: The aim was to investigate the prevalence of self-reported sleep
complaints in New Zealand adults and determine the independent association of
sleep complaints with adverse health outcomes. DESIGN: We used 2002/03 New
Zealand Health Survey data (n = 12,500 adults, >=15 years). The prevalence of
self-reported sleep complaints was estimated by ethnicity. The relationship
between sleep complaints and mental health, physical health and health risk
behaviors were investigated using multivariable logistic regression models.
RESULTS: The prevalence of each sleep complaint measure was highest for the
indigenous Maori population (23.6% reported 'any' sleep complaint; 10.3% reported
multiple sleep complaints). Reporting 'any' sleep complaint was associated with
higher odds of poorer mental health, diagnosed high blood pressure, diagnosed
diabetes, diagnosed heart disease, poor/fair self-rated health, obesity, current
smoking, and hazardous drinking. CONCLUSION: The higher prevalence of sleep
complaints among Maori and the consistent association with poor health suggests a
potential role for suboptimal sleep in ethnic health inequities.
PMID- 28412839
TI - Awareness and Knowledge of Ovarian Cancer Symptoms and Risk Factors: A Survey of
Jordanian Women.
AB - Ovarian cancer accounts for 3% of all female cancers and has a high mortality
rate among gynecological malignancies. Early diagnosis carries a high survival
rate of 93%. So, this study was carried out to assess the knowledge and awareness
of Jordanian women about ovarian cancer symptoms and risk factors. A cross
sectional survey design was used; 896 women completed the survey. The mean of
total symptoms recognized was low at level of 3.2 ( SD = 2.7) out of 10. The
three highest known symptoms among women were as follows: extreme fatigue
(43.2%), back pain (42.4%), and persistent pain in pelvic area (40.7%). The most
commonly known risk factor was smoking (68.4%), followed by having ovarian
cyst(s) (59.7%). Hence, with the absence of an effective screening program, a
national awareness campaign is urgently needed to improve the public's
understanding of symptoms and risk factors and increasing women's confidence in
symptom recognition.
PMID- 28412840
TI - Anti-proliferative and pro-apoptotic effects of cinobufagin on human breast
cancer MCF-7 cells and its molecular mechanism.
AB - Cinobufagin (CBF) is an active ingredient isolated from Venenum Bufonis extracted
and dried from the secretory glands of Bufo gargarizans Cantor. The purpose of
the study was to investigate the effects and underlying mechanisms of CBF on
human breast cancer MCF-7 cells in vitro. Our results showed that CBF exhibited
obvious cytotoxicity on MCF-7 cells in a dose- and time-dependent manner, as
indicated by CCK-8 assays. Also, Hoechst 33258 staining and flow cytometry assays
showed that CBF strongly induced MCF-7 cell apoptosis and G1 phase arrest. In
addition, further molecular mechanistic investigation demonstrated that
cinobufagin significantly increased Bax expression, decreased Bcl-2 expression
level and up-regulated the ratio of the pro-apoptosis/anti-apoptosis protein
Bax/Bcl-2, which were demonstrated by RT-qPCR and western blot assays. Taken
together, our data confirm that CBF inhibits growth and triggers apoptosis of MCF
7 cells by affecting the expression of Bax and Bcl-2 in vitro.
PMID- 28412841
TI - A new pyranoxanthone from Garcinia nervosa.
AB - Phytochemical studies on the stem bark of Garcinia nervosa has resulted in the
discovery of one new pyranoxanthone derivative, garner xanthone (1) and five
other compounds, 1,5-dihydroxyxanthone (2), 6-deoxyisojacareubin (3), 12b-hydroxy
des-D-garcigerrin A (4) stigmasterol (5), and beta-sitosterol (6). The structures
of these compounds were elucidated with the aid of spectroscopic techniques, such
as NMR and MS. The crude extracts of the plant were assessed for their
antimicrobial activity.
PMID- 28412842
TI - Four new Sesquiterpenoids from Sphaeranthus indicus.
AB - Isolation and characterisation of two new eudesmanolides, 5alpha-hydroperoxy
7alpha-hydroxy-isosphaerantholide (1) and (11alpha,13-dihydro-7alpha
hydroxyfrullanolide-13-yl)-adenine (2) from the flower heads of Sphaeranthus
indicus are described. In addition, 5alpha-hydroxy-isosphaerantholide (3) and
11alpha,13-dihydro-eudesman-3,5,7-triene-6alpha-12-olide (4) are reported first
time as a metabolite of S. indicus and as a natural product, respectively. The
structures of these compounds were established from rigorous analysis of their
high-resolution mass, IR, UV, 1H NMR, 13C NMR and 2D NMR spectral data.
PMID- 28412843
TI - Continuous ECG Monitoring in Patients With Acute Coronary Syndrome or Heart
Failure: EASI Versus Gold Standard.
AB - The purpose of the study was to compare the EASI system with the standard 12-lead
surface electrocardiogram (ECG) for the accuracy in detecting the main
electrocardiographic parameters (J point, PR, QT, and QRS) commonly monitored in
patients with acute coronary syndromes or heart failure. In this observational
comparative study, 253 patients who were consecutively admitted to the coronary
care unit with acute coronary syndrome or heart failure were evaluated. In all
patients, two complete 12-lead ECGs were acquired simultaneously. A total of
6,072 electrocardiographic leads were compared (3,036 standard and 3,036 EASI).
No significant differences were found between the investigate parameters of the
two measurement methods, either in patients with acute coronary syndrome or in
those with heart failure. This study confirmed the accuracy of the EASI system in
monitoring the main ECG parameters in patients admitted to the coronary care unit
with acute coronary syndrome or heart failure.
PMID- 28412844
TI - Compounds with inhibitory activity on peristalsis from the seeds of Holarrhena
antidysenterica.
AB - Eight compounds were isolated from the seeds of Holarrhena antidysenterica
Wall.ex A.DC. On the basis of physico-chemical properties and spectroscopic data,
holarrhenanan (1) was identified as a new compound, compounds 2-3 were isolated
from H. antidysenterica for the first time, and five known compounds were also
obtained. Inhibitory effects of some compounds and extracts to the intestinal
peristalsis were evaluated. Results showed that the extracts and compounds 4, 6
exhibited remarkable inhibitory effects with tension inhibition rate of 32.77,
32.77% and amplitude inhibition rate of 59.51, 55.98%, respectively on the vitro
rabbit intestinal peristalsis.
PMID- 28412845
TI - Fetal and maternal temperatures during labor and delivery: a prospective
descriptive study.
AB - OBJECTIVE: The objective of this study is to study the fetal scalp temperature
(FST) and maternal axillary temperature (MAT) during vaginal delivery relative to
progression of labor, uterine contractions (UC) and epidural analgesia (EDA), and
to construct normal temperature reference ranges related to stage of labor.
MATERIAL AND METHODS: Temperatures were recorded continuously in labor of 132
women with a bi-metal temperature sensor attached to the axilla (MAT) and a
similar sensor mounted in a scalp electrode (FST). The temperature data were
stored electronically and analyzed offline at cervical dilatations of 2-3, 5, 7
8, and 10 cm, and at full retraction. The FST was read before, at increasing, at
peak, at decreasing, and after UC. The MAT and FST curves were compared with
mixed-effect models statistics for repeated measurements. A two-tailed p <.05 was
considered significant. RESULTS: The FST did not vary during UC (p = .24). Both
FST and MAT increased linearly by progression of labor (both p < .001). The
increases in temperatures were greater with EDA than without (p < .001).
CONCLUSIONS: During UC, the FST showed no alteration. Both FST and MAT increased
significantly by progression of labor, and significantly more in the presence of
EDA. The presented normal temperature reference ranges can be used for future
research.
PMID- 28412846
TI - Changes in levator hiatus dimensions during pregnancy and after delivery in
nulliparas: a prospective cohort study using 3D transperineal ultrasound.
AB - PURPOSE: The purpose of this study was to investigate the changes that occur in
the levator ani muscle (1) during pregnancy and (2) after labor depending on the
mode of delivery in a cohort of nulliparas. MATERIALS AND METHODS: A prospective
cohort longitudinal study, consisting of 84 primiparas who were examined and
recruited in an antenatal clinic was conducted. All participants were submitted
to a real-time three-dimensional (3D) ultrasonographic evaluation of the levator
ani at (1) 12, (2) 22, and (3) 32 weeks of pregnancy (4) and 4-6 months
postdelivery. The 3D volumes were acquired and stored for an offline analysis.
RESULTS: Data from 59 women with at least two measurements were available for
analysis. 35 women were delivered vaginally and 24 via cesarean section. There
was a statistical increase in the dimensions of the levator hiatus at each
pregnancy trimester when compared to the measurements of the previous trimesters.
After vaginal delivery, hiatal dimensions increased compared to the third
trimester measurements; after cesarean section, hiatal dimensions decreased.
CONCLUSIONS: This study supports that in primiparas, the dimensions of the
levator hiatus increase significantly during pregnancy and subsequently either
increase further after vaginal delivery or decrease to the first-trimester levels
after cesarean section.
PMID- 28412847
TI - Circumcision bleeding complications: neonatal intensive care infants compared to
those in the normal newborn nursery.
AB - PURPOSE: To determine if a significant difference exists in the bleeding
complications following circumcision in neonates admitted to neonatal intensive
care unit (NICU) versus the normal newborn nursery (NNN). MATERIALS AND METHODS:
Observational cohort study of 260 infants undergoing circumcision with Gomco
clamp. Vitamin K was given to neonates at delivery. Demographic data, procedural
characteristics, bleeding complications, and interventions were recorded. The
bleeding rates of the two groups were compared using chi square. RESULTS: NICU
neonates experienced increased bleeding complications versus NNN neonates (22%
vs. 9.6%, p = .029). No differences were found regarding gestational age at
delivery, age at circumcision, and birth weight. Neonates with circumcision
performed at >=5 days of life experienced increased rates of bleeding
complications versus those performed at <=4 days (28% vs. 10.3%, p = .023). All
neonates with circumcision performed >=5 days of life were initially admitted to
the NICU. CONCLUSION: NICU neonates had increased rate of bleeding complications
following circumcision when compared to the NNN neonates. There was an increased
rate of bleeding complications in neonates who undergo circumcision at >=5 days
of life. Further research may help to determine if redosing of vitamin K or
variations in the circumcision procedure are necessary for circumcision at >4
days of life.
PMID- 28412848
TI - Proteomic profile of serum of pregnant women carring a fetus with Down syndrome
using nano uplc Q-tof ms/ms technology.
AB - INTRODUCTION: Prenatal diagnosis of Down syndrome (DS) is based on the calculated
risk of maternal age, biochemical and ultrasonographic markers and recently by
cfDNA. Differences in proteomic profiles may give an opportunity to find new
biomarkers. OBJECTIVE: Characterize proteome of serum of mothers carrying DS
fetus. MATERIAL AND METHODS: Blood serum samples of three groups of women were
obtained, (a) 10 non-pregnant, (b) 10 pregnant with healthy fetus by ultrasound
evaluation, (c) nine pregnant with DS fetus. Sample preparation was as follows:
Albumin/IgG depletion, desalting, and trypsin digestion; the process was
performed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1 and
ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOT
algorithm and UNIPROT-Swissprot database. RESULTS: Each group showed different
protein profiles. Some proteins were shared between groups. Only sera from
pregnant women showed proteins related to immune and clot pathways. Mothers with
DS fetus had 42 specific proteins. CONCLUSIONS: We found a different serum
protein profile in mothers carrying DS fetuses that do not reflect expression of
genes in the extra chromosome. Further studies will be necessary to establish the
role of these proteins in aneuploid fetus and analyze their possible use as
potential biomarkers.
PMID- 28412849
TI - Maternal hemodynamic changes and predictors of poor obstetric outcome in women
with rheumatic heart disease: a five-year observational study.
AB - OBJECTIVE: To assess prospectively the maternal cardiovascular hemodynamic
changes and obstetric outcome in women with rheumatic heart disease (RHD) and to
detect predictors of poor outcome. METHODS: This prospective observational study
included 204 pregnant patients with RHD who were divided into two groups;
successful pregnancy group with living fetus (n = 126) and poor obstetric outcome
group with fetal or neonatal loss (n = 78). Hemodynamic changes, maternal and
fetal outcome were assessed and recorded. RESULTS: There was a highly significant
difference between the two groups regarding disease criteria with more women
suffering from stenotic lesions (mitral and aortic), pulmonary hypertension,
previous heart failure, receiving cardiac medications and higher NYHA class (III
and IV) in the poor obstetric outcome group (p < .001). These patients were more
prone to maternal and fetal morbidity. Maternal age above 28 years, body mass
index higher than 28, mean pulmonary artery pressure higher than 50 mmHg, NYHA
class III-IV and development of heart failure or cyanosis are predictors of poor
outcome (p < .001). CONCLUSIONS: Increased maternal age and body mass index
together with NYHA class III-IV, significant pulmonary hypertension, reduced
ejection fraction and development of heart failure during pregnancy are strong
predictors of poor maternal and fetal outcome.
PMID- 28412850
TI - Assessment of hysteroscopic role in management of women with recurrent pregnancy
loss.
AB - OBJECTIVES: To assess the hysteroscopic value in the management of intrauterine
lesion in women with recurrent pregnancy loss. METHODS: This study was done in
Ain Shams Maternity Hospital after the approval of the research Ethics Committee,
during the period between August 2014 and December 2015 where 200 nonpregnant
women with a history of three or more consecutive unexplained first and second
trimester miscarriages before 20 weeks were recruited from recurrent miscarriage
clinic. A written informed consent was obtained from all women before
participation. RESULTS: This current study was conducted in Ain Shams University
Maternity Hospital during the period between August 2014 to May 2015 a total of
200 women with history of recurrent miscarriage were included in the study.
Regarding the results of this study the mean age was 30.5(5.7), the mean number
of previous abortion 3(3-5) the mean number of the first trimesteric abortion was
2 with range (2-2) the mean number of second trimesteric abortion was 2 with
range (1-2). In this study, 88% of patients were nullipara. It was also found
that hysteroscopic findings were found in 58.5%. Uterine anomalies was present in
21%, including septate uterus and intrauterine adhesion (IUAs) were present in
12.5%. Endometrial polyps were present in 8.5%, bicornute uterus in 4.5%,
unicornuate uterus in 4.5% while submucous myomas were present in 7.5%. It was
found that 48.5% need hysteroscopic intervention including 21% need septectomy
12.5% need adhesiolysis, 6.5% need myomectomy while 8.5% need polypectomy. The
study found that no statistically significant difference between patients with
normal hysteroscopic finding and patients with abnormal hysteroscopic finding as
regard age, time of previous abortion and number of previous abortion. But there
was statistically significant difference as regard number of previous delivery
and abnormal HSG. CONCLUSIONS: It appears that hysteroscopy is a useful tool in
the diagnosis and treatment of the causes of recurrent miscarriage that can be
performed safely without anesthesia in most cases. The prevalence of uterine
anomalies in patients with recurrent miscarriages is 54.5%, septate uterus is the
most common anomaly and for this reason uterine anomalies should be
systematically assessed in patients with recurrent miscarriage.
PMID- 28412851
TI - Cervical pessary in the prevention of preterm births in multiple pregnancies with
a short cervix: PRISMA compliant systematic review and meta-analysis.
AB - BACKGROUND: Preterm births occur frequently in multiple pregnancies with a short
cervix. The cervical pessary is a potential intervention for prevention of
preterm births. OBJECTIVE: To assess the effectiveness of cervical pessary in the
prevention of preterm births in multiple pregnancies with a short cervix (<25
mm). SEARCH STRATEGY: Major databases from 2006 to 20th November 2016 were
searched for relevant terms. SELECTION CRITERIA: We included randomized
controlled trials that assessed the effectiveness of cervical pessary on
pregnancy outcomes in multiple pregnancies with a short cervix. DATA COLLECTION
AND ANALYSIS: Risk ratio was used as the summary measure with random effects
model. We assessed heterogeneity between studies using the I2 index. Quality
assessment was done based on Cochrane Handbook Method. MAIN RESULTS: Pooled data
showed no benefit of using cervical pessary in the prevention of preterm births,
birth weights less than 1500 g, less than 2500 g, adverse neonatal events and
fetal/neonatal deaths in twin pregnancies with a short cervix. CONCLUSION: We are
unable to show benefit of using cervical pessary in preventing preterm births in
twin pregnancies with a short cervix. However, as cervical pessary is a
reasonable intervention, there is a need for more randomized controlled trials in
this area.
PMID- 28412852
TI - Transitional hemodynamics in infants of diabetic mothers by targeted neonatal
echocardiography, electrocardiography and peripheral flow study.
AB - OBJECTIVE: Metabolic alterations of intrauterine environment in diabetes mellitus
(DM) lead to fetal cardiac dysfunctions that can persist after birth. The aim of
the study was to assess the cardiovascular adaptation in infants born to diabetic
mothers (IDM) with different degrees of glycometabolic control, in relation to
revised guidelines for diagnosis of DM and quality improvements in neonatal care.
MATERIALS AND METHODS: An observational case-control study was conducted on IDM
with gestational, type 1 and type 2 DM. Relevant maternal and neonatal
anamnestic, clinical and laboratory data were analyzed. Electrocardiographic and
echocardiographic analyses, including structural and systo-diastolic evaluation,
were performed. RESULTS: In 68 IDM enrolled, we observed a lower incidence of
negative perinatal outcome than expected. Comparing to non-IDM, they presented
larger fetal shunts, higher pulmonary pressures, early and atrial wave
velocities. At 72 hours, kinesis and heart rate variability remained low.
Cerebral blood flow velocities were higher. The most serious impairment of
transition was in pregestational IDM. CONCLUSION: Maternal DM impaired neonatal
transitional hemodynamics also in asymptomatic IDM with good glycometabolic
control. These results confirm the need for an early cardiologic and
cerebrovascular evaluation, to identify IDM with delayed maturation at risk of
worse long-term metabolic, cardiovascular, and neurodevelopmental outcome.
PMID- 28412854
TI - Oxidative stress in preeclamptic mother - newborn dyads and its correlation with
early neonatal outcome - a case control study.
AB - BACKGROUND: Preeclamptic mothers are likely to have increased oxidative stress
during pregnancy which can adversely affect the outcome in their neonates.
OBJECTIVES: To measure the oxidative stress in preeclamptic mother- newborn dyads
and correlate it with the immediate neonatal outcome. METHODS: This case control
study conducted in a tertiary care teaching hospital, South India included 71
preeclamptic mothers - newborn dyads (cases) and 72 normal mothers - newborn
dyads (controls). Biochemical parameters including total antioxidant status
(TAS), protein carbonyls and malondialdehyde levels (MDA) were measured in both
maternal and cord blood. Association between these oxidative stress parameters
and early neonatal outcome was studied. RESULTS: All oxidative stress markers
were higher in the preeclampsia group compared to the controls. Cord blood
protein carbonyl levels had significant correlation with maternal levels.
Prematurity, low-birth weight, respiratory distress syndrome (RDS), early onset
sepsis (EOS) and intra-uterine growth restriction (IUGR) were more among cases.
Early neonatal outcomes like death, IUGR, EOS, and RDS had significant
correlation with protein carbonyl levels among the cases. CONCLUSIONS: Oxidative
stress is increased in preeclamptic mother - newborn dyads. Increased protein
carbonyl levels in preeclampsia correlate with adverse early neonatal outcome.
PMID- 28412853
TI - Nitrogen behaviour during thermal drying of mechanically dewatered biosludge from
pulp and paper industry.
AB - An ongoing call to implement a circular economy is underway in the European
Union, and a specific attention has been placed on the forest industry, which
seeks additional recycling routes for its side streams, including biosludge.
Biosludge is often dried and incinerated, thus wasting the nitrogen contained
therein. This paper describes a study in which the release of nitrogen during
thermal drying, the impact of the drying temperatures of 130 degrees C, 180
degrees C, and 210 degrees C on the mass of ammonia released, and the potential
for recovery of nitrogen from biosludge were examined. The results indicate that
1310-1730 mg kgTS-1 of nitrogen was released, which corresponded to 56-74% of the
soluble nitrogen in biosolids or 4.0-5.3% of the total nitrogen. Of this released
nitrogen, 83-85% was identified in condensate and absorbing water, thus
indicating a high potential for recovering nitrogen from biosludge.
PMID- 28412855
TI - Decreased TLR4 expression on monocytes may cause regulatory T cells abnormality
in patients with primary immune thrombocytopenia.
AB - Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune
dysfunctions including T helper type 1 cell (Th1) polarization and regulatory T
cells (Tregs) deficiency. This study aimed to determine the effects of TLR4 on
Treg differentiation and the cytokine production of peripheral blood mononuclear
cells (PBMCs) from patients with ITP. We found that expression of TLR4 on
monocytes was significantly decreased in patients with active ITP than that in
healthy controls and it had positive correlation with platelet count. However,
there was no expression of TLR4 on CD4+ T cells. The result of further
experiments in vitro showed that lipopolysaccharide (LPS) stimulation could
enhance TLR4 expression on monocytes. Additionally, activation of TLR4 with LPS
could promote differentiation of Treg cells and anti-TLR4 attenuated this effect.
There was no significant difference about Th17 cells among three subgroups.
However, the Th17/Treg cell ratio was decreased after stimulation with LPS and
increased with anti-TLR4. Moreover, activation of TLR4 with LPS could
significantly promote the secretion of interleukin-10 (IL-10) and transforming
growth factor-beta1 (TGFB1), while anti-TLR4 significantly suppressed the
secretion of them. Nevertheless, the secretion of IL-17A did not reach the
statistical difference among three subgroups. In summary, decreased TLR4 appears
to cause Tregs abnormality in ITP by modulating Tregs differentiation and
immunoregulatory cytokines.
PMID- 28412856
TI - Investigating the role of IL-33 in the pathogenesis of Behcet's Disease.
AB - OBJECTIVES: Behcet's disease (BD) is an inflammatory disease, characterized by
oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations.
Increased release of several cytokines may play a role in the inflammatory stages
of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role
in inflammation. We analyzed serum IL-33 concentration in BD patients to assess
its possible role in the pathophysiology of this disease. METHODS: The study
included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18
matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked
immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 +/-
2.81 pg/ml in the BD patients (6.16 +/- 2.94 pg/ml in the active stage and 2.86
+/- 0.54 pg/ml in the inactive stage) and 2.88 +/- 0.42 pg/ml in the healthy
controls. Serum IL-33 levels were significantly higher in patients with BD
compared with the healthy controls (p < 0.01). In active Behcet patients with
arthritis the mean serum IL-33 level was higher but this finding was not
statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant
role of in the pathogenesis of BD.
PMID- 28412857
TI - Prevalence of diminished ovarian reserve in Chinese women with polycystic ovary
syndrome and sensitive diagnostic parameters.
AB - OBJECTIVES: To assess the prevalence of diminished ovarian reserve (DOR) in
patients with polycystic ovary syndrome (PCOS) in China, and to search for
sensitive diagnostic parameters. METHODS: Three hundred and thirty eight PCOS
women aged 20-39 years were recruited. Basic characteristics, follicle
stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone
and anti-Mullerian hormone (AMH) were measured. The best indices to diagnose PCOS
with DOR were assessed. RESULTS: The prevalence of DOR in our Chinese PCOS
patients was 16.9%. The level of E2 and FSH and the FSH/LH ratio had a positive
correlation with PCOS and DOR (OR > 1, p < 0.05) independent of age and
testosterone, while AMH and baseline antral follicle count had a negative
correlation (OR < 1, p < 0.05). AMH was a good parameter to diagnose PCOS with
DOR, the cutoff was 2.53 ng/ml, with sensitivity 92.5%, specificity 73.7% and
area under curve 0.932. AMH had a significant positive correlation with LH (r =
0.016, p < 0.05) and testosterone (r = 0.209, p < 0.01), while had significant
negative correlation with age (r=-0.140, p < 0.05), FSH (r=-0.229, p < 0.01) and
FSH/LH ratio (r=-0.240, p < 0.01). CONCLUSIONS: In our study, AMH was a sensitive
parameter to diagnose PCOS with DOR, but to improve the accuracy it will still
need further studies.
PMID- 28412858
TI - Profile of lipophilic antioxidants in the by-products recovered from six
cultivars of sour cherry (Prunus cerasus L.).
AB - The content of tocochromanols and carotenoids in kernels recovered from fruit
pits of six sour cherry (Prunus cerasus L.) cultivars was studied. The highest
concentration was noted for gamma-T (23.50-52.76 mg/100 g dry weight basis (dw)).
Considerably, lower amounts compared to gamma-T were detected for alpha-T, delta
T and alpha-T3 (5.74-13.33, 2.74-4.54 and 0.30-1.16 mg/100 g dw, respectively).
The beta-T and gamma-T3 were quantified only in minor levels. The total amount of
tocochromanols was in the range 41.69-63.48 mg/100 g dw. The levels of total
carotenoids ranged between 0.17 and 0.39 mg/100 dw. The concentration of
tocochromanols and carotenoids in kernels of different sour cherries is cultivar
dependent. A significant correlation (r = 0.985, p < 0.001) has been observed
between the total content of tocochromanols in kernels and scavenging of free
radicals DPPH by native lipophilic antioxidants in the by-products of sour
cherry.
PMID- 28412859
TI - Determination and quantification of carotenoids in sea sponges Raspaciona
aculeata and Dictyonella marsilii present in the Ganzirri Lake (Messina), Italy.
AB - Considering the crucial role of carotenoids exploitable both as nutraceuticals
and also as dyes in food industry, there are many efforts in seeking for new
sources of these pigments, especially in the marine world. In this study, for the
first time, we extracted carotenoids from sea sponges Raspaciona aculeata and
Dictyonella marsilii taken from Ganzirri Lake Messina (Italy). The determination
and quantification of carotenoids was made by UPLC-PDA-MS. Remarkable results
concern renieratene content in R. aculeate found to be over 2570 ppm.
PMID- 28412860
TI - Modeling vascular inflammation and atherogenicity after inhalation of ambient
levels of ozone: exploratory lessons from transcriptomics.
AB - BACKGROUND: Epidemiologic studies have linked inhalation of air pollutants such
as ozone to cardiovascular mortality. Human exposure studies have shown that
inhalation of ambient levels of ozone causes airway and systemic inflammation and
an imbalance in sympathetic/parasympathetic tone. METHODS: To explore molecular
mechanisms through which ozone inhalation contributes to cardiovascular
mortality, we compared transcriptomics data previously obtained from
bronchoalveolar lavage (BAL) cells obtained from healthy subjects after
inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples
from 11 published studies of patients with atherosclerotic disease using the
Nextbio genomic data platform. Overlapping gene ontologies that may be involved
in the transition from pulmonary to systemic vascular inflammation after ozone
inhalation were explored. Local and systemic enzymatic activity of an overlapping
upregulated gene, matrix metalloproteinase-9 (MMP-9), was measured by zymography
after ozone exposure. RESULTS: A set of differentially expressed genes involved
in response to stimulus, stress, and wounding were in common between the ozone
and most of the atherosclerosis studies. Many of these genes contribute to
biological processes such as cholesterol metabolism dysfunction, increased
monocyte adherence, endothelial cell lesions, and matrix remodeling, and to
diseases such as heart failure, ischemia, and atherosclerotic occlusive disease.
Inhalation of ozone increased MMP-9 enzymatic activity in both BAL fluid and
serum. CONCLUSIONS: Comparison of transcriptomics between BAL cells after ozone
exposure and various cell types from patients with atherosclerotic disease
reveals commonly regulated processes and potential mechanisms by which ozone
inhalation may contribute to progression of pre-existent atherosclerotic lesions.
PMID- 28412861
TI - The association between progestins, nuclear receptors expression and inflammation
in endometrial stromal cells from women with endometriosis.
AB - Endometriosis is an inflammatory disease and nuclear receptors play a crucial
role in mediating the inflammatory response. In endometrial stromal cells (ESC),
nuclear receptors expression can be influenced by the local environment.
Progestins are first-line, on-label treatments of endometriosis that may have
direct effects on endometriotic lesions through these nuclear receptors.
Therefore, we investigated whether there was an association between nuclear
receptors expression and the influence of progestins on inflammatory cytokines
production in a preliminary, in vitro study with primary cultures. ESC from
endometrial biopsies of six subjects with histologically confirmed endometriosis
were treated for 6 h with medium alone or with TNF-alpha (10 or 100 ng/ml) in the
presence of dienogest (DNG), medroxyprogesterone acetate (MPA) and norethisterone
acetate (NETA) 10-5 M. The progestin-mediated change in IL6, IL8 and MCP-1 mRNA
transcription was measured, as was the PRA, PRB, GR, AR and MCR protein
expression. The change (medium versus TNF-alpha 10 ng/ml and medium versus TNF
alpha 100 ng/ml) in IL6 mRNA transcription was positively associated with the
change in PRB, but not PRA with both DNG and NETA treatment. The change in IL8
mRNA was negatively associated with AR expression in the presence of NETA. The
change in MCP-1 mRNA expression was positively associated with GR expression and
negatively associated with MCR after MPA treatment. The associations between the
change in cytokines mRNA expression and nuclear receptors protein expression in
response to progestins activity may indirectly suggest different activities of
these compounds at a local level worthy of further investigations.
PMID- 28412863
TI - Oxidized lipoprotein lipids and atherosclerosis.
AB - Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP),
which are known to impair normal physiological functions and stimulate
atherosclerotic processes. Recent evidence indicates that plasma lipoproteins are
active carriers of LOP, low-density lipoprotein (LDL) directing transport toward
peripheral tissues, and high-density lipoprotein (HDL) being active in the
reverse transport. It has been proposed that the lipoprotein-specific transport
of LOP could play a role in atherosclerosis-related effects of LDL and HDL. This
article gives an overview of the present knowledge of lipoprotein LOP transport
and its association with the risk of atherosclerosis and cardiovascular diseases
(CVD). Evidence of the significance of lipoprotein LOP transport comes mainly
from studies of physiological oxidative stress and is supported by studies of the
functionality apolipoprotein A-1 mimetic peptides. A large body of data has
accumulated indicating that lipoprotein LOP transport is connected to the risk of
atherosclerosis. While high levels of LOP carried by LDL are indicative of
elevated risk, high LOP level in HDL appears to associate with protection. If
confirmed, the proposed lipoprotein LOP transport function would affect
conception of the etiology of atherosclerosis, but would not conflict current
views of the pathophysiological mechanisms. It could open new perspectives, such
as the dietary origin of LOP, and the protective function of HDL in clearance of
LOP. Focusing on LOP could give additional tools especially for prevention and
diagnosis, but would not radically change the management of atherosclerosis and
CVD.
PMID- 28412862
TI - Impact of transvaginal hydrolaparoscopy ovarian drilling on ovarian stromal blood
flow and ovarian volume in clomiphene citrate-resistant PCOS patients: a case
control study.
AB - Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in
gynecology. In PCOS patients vascularization parameters are altered. Transvaginal
hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS
patients. In this study, we assessed the effect of ovarian drilling using THL on
ovarian volume (OV) and vascularization index (VI) using 3D power Doppler
ultrasonography in CC-resistant PCOS patients. A case-control study on 123 CC
resistant PCOS women who underwent THL ovarian drilling was performed. Patients
underwent 3D ultrasound and power Doppler to measure VI, flow index (FI),
vascularization flow index (VFI) and to evaluate OV before and after the
procedure, at six months, and on the early follicular phase of the menstrual
cycle. After THL ovarian drilling, OV and power Doppler flow indices were
significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72
cm3, p < 0.01; VI: 2.50 versus 4.81, p < 0.01; VFI: 1.10 versus 2.16, p < 0.01;
FI: 32.05 versus 35.37, p < 0.01). In conclusion, THL ovarian drilling seems to
reduce OV and 3D power Doppler indices, and could therefore be a viable
alternative to LOD in PCOS patients resistant to medical therapy.
PMID- 28412864
TI - Cutaneous allergic drug reactions: update on pathophysiology, diagnostic
procedures and differential diagnosic.
AB - Important changes in the understanding and management of drug hypersensitivity
reactions during the last years result from the increasing importance of
biologics in medical practice, which differ in their spectrum of adverse drug
reactions (ADRs) from the classical covalent drugs. With regard to covalent
drugs, ampicillin and amoxicillin as well as clavulanic acid play an increasing
role among ADRs to betalactam antibiotics. Fluoroquinolones are mainly the cause
of anaphylactic and photosensitivity reactions. Especially in allergic reactions
to NSAIDs, pseudoallergic reactions should be considered in the differential
diagnosis. In opposite to the main cutaneous allergic drug reactions such as
urticaria or maculopapular skin rash, in which antibiotics are the main culprits,
in severe drug allergic reactions such as SJS (Stevens-Johnson Syndrome), TEN
(Toxic Epidermal Necrolysis), or DRESS (Drug Reaction with Eosinophilia and
Systemic Symptoms) Syndrome, compounds like allopurinol and anticonvulsants are
the main causes. Similar mutations in the IL36R gene, which were found in both
patients with an AGEP (Acute Generalized Exanthematous Pustulosis) and pustular
psoriasis, make the differential diagnosis more difficult and raise the question
whether there is a difference between these diseases or whether AGEP is not just
a drug induced pustular psoriasis. Finally, some special aspects of side effects
of biologics and targeted therapies respectively are discussed.
PMID- 28412865
TI - Strength adaptation to squat exercise is different between Caucasian and South
Asian novice exercisers.
AB - This study compared the progression of muscular strength (MS) adaptation between
age-matched Caucasian (CAUC) and South Asian (SOU) men during 6 weeks (3* week-1)
of resistance training. MS was determined pre and post intervention by 3
repetition maximum (3RM) strength tests, and data were analysed using repeated
measures ANOVA. Pre-intervention upper and lower body 3RM were similar between
groups and both upper and lower body 3RM increased in CAUCs (P < .001) and SOUs
(P < .001) following resistance training. However, lower body strength adaptation
(3RM) was higher in CAUCs compared with SOUs (P = .002). There was a significant
group * time interaction in strength progression of the squat exercise (P = 0.03)
from session 7 through to 18 (completion). The present study offers novel but
provisional data that lower body strength adaptation is slower in SOU than CAUC
men despite comparable adaptation to upper body strength.
PMID- 28412866
TI - Comparison of the morphokinetic parameters of embryos according to ovarian
reserve in IVF cycles.
AB - The aim of this study is to evaluate the impact of ovarian reserve and age of
women on early morphokinetic parameters of embryos with a time-lapse monitoring
system. In total, 197 infertile couples with poor ovarian reserve (Group 1, n =
41), normal ovarian reserve (Group 2, n = 59), or polycystic ovaries (Group 3, n
= 97) were included. The time from insemination to the following events were
analyzed: pronuclear fading (Pnf) and cleavage to 2, 3, 4 and 5 cells. The
optimal ranges for morphokinetic parameters of t5, s2 and cc2 in each group were
also evaluated. In total, 1144 embryos were evaluated. Morphokinetic parameters
did not differ statistically between the groups. Data were analyzed according to
different age groups (20-30, 30-40, >40). The morphokinetic parameters did not
differ statistically in Group 1 and 3. In Group 2, the times from insemination to
tPnf, t2, t3, t4 were significantly shorter in the younger age group than the
older age group (p < 0.05). The percentages of optimal embryos, according to t5,
s2 and cc2, did not differ statistically between the groups. In conclusion,
ovarian reserve did not seem to affect the morphokinetic parameters of embryos.
PMID- 28412867
TI - Weight gain, body image and sexual function in young patients treated with
contraceptive vaginal ring. A prospective pilot study.
AB - INTRODUCTION: Oral contraceptives could induce mood changes. As far as our
knowledge, there are no studies in literature that have examined the role of
vaginal contraception in self-perceived body image. AIM: To evaluate the effects
of intravaginal contraception on weight gain and perceived body image in relation
with the Beck's Depression Inventory questionnaire (BDI) and the McCoy Female
Sexuality Questionnaire (MFSQ). METHODS: Twenty-one adult (18-35 years old)
eumenorrheic (menstrual cycle of 25-35 days), lean (body mass index - BMI - of 19
25 kg/m2) women who were referred for hormonal contraception were administered
the Stunkard Figure Rating Scale (FRS), BDI and MFSQ. Subjects were studied in
basal condition and after 6 months of therapy with vaginal contraception
(NuvaRing(r); Organon-Schering-Plough Italia, Milan, Italy). MAIN OUTCOME
MEASURES: BMI, FRS, MFSQ and BDI. RESULTS: After 6 months of therapy with
NuvaRing(r), both body weight (60.0 +/- 8.3; p = 0.050) and BMI (22.1 +/- 3.1; p
= 0.028) slightly, but statistically, increased. FRS and BDI showed no
differences after the vaginal contraception. Hormonal contraception was
associated with a significant decrease in the two-factor Italian MFSQ score.
CONCLUSIONS: Vaginal ring seems a good alternative to other hormonal
contraceptive not significantly altering the female sexuality and not influencing
the FRS and BDI.
PMID- 28412868
TI - Prevalence of pre-high blood pressure and high blood pressure among non
overweight children and adolescents using international blood pressure references
in developed regions in China.
AB - BACKGROUND: There is a lack of data on the prevalence of pre-high blood pressure
(PreHBP) and high blood pressure (HBP), based on recent international blood
pressure references, in non-overweight children and adolescents. AIM: To describe
the prevalence of PreHBP and HBP in non-overweight children and adolescents in
developed regions of China. SUBJECTS AND METHODS: In total, 588 097 non
overweight children and adolescents aged 6-17 years from the National Surveys on
Chinese Students' Constitution and Health in 2015 were included. RESULTS: The
prevalence of PreHBP was 13.41% and subjects in urban areas had a higher
prevalence of PreHBP (14.14%) than those in rural areas (12.92%). Subjects in
regions with a high (13.56%) or moderate (13.61%) socioeconomic status showed a
higher prevalence of PreHBP than those in regions with a relatively low
socioeconomic status (12.76%). A similar pattern was found for the prevalence of
HBP, and the prevalence of HBP was 18.25% for all participants, 20.55% for
subjects in urban areas, 16.71% in rural areas, 18.76% in high socioeconomic
areas, 18.62% in moderate socioeconomic areas and 16.70% in relatively low
socioeconomic areas. CONCLUSION: A large proportion of non-overweight children
and adolescents had elevated blood pressure and there were urban-rural and
socioeconomic disparities in the prevalence of elevated blood pressure.
PMID- 28412869
TI - A novel Salvialactomine from the callus culture of Salvia santolinifolia Boiss.
AB - A novel compound Salvialactomine (1) along with two other unusual occurring
natural products Pentatriacontanoic acid 1, 3-dihydroxypropyl ester (2) and 5
Methylflavone (3) were isolated from the callus of Salvia santolinifolia Boiss.
Callus was initiated on MS medium containing NAA (0.5 mg/L) and further sub
cultured on MS medium supplemented with NAA with BA (0.5 + 1.5 mg/L). The
structures of isolated compounds were determined by using mass spectrometry, 1D,
and 2D-NMR techniques. Compounds 1, and 3 were tested for two different cancer
cell lines, i.e. Hela (Cervical cancer cell) and PC-3 (Prostate cancer cells).
IC50 was found as > 30 using Doxorobicin (0.912 +/- 0.12 MUmol L-1) as a
standard.
PMID- 28412871
TI - The effect of oil and water-soluble contrast medium in hysterosalpingography on
thyroid function.
AB - Hysterosalpingography (HSG) using iodinated contrast medium is X-ray diagnostic
test that examines the inside of the uterus and fallopian tubes in infertile
women. In this study, we compared thyroid function (thyroid stimulating hormone:
TSH and free-T4: FT4 levels) after HSG with an oil-soluble contrast medium (OSCM)
and a water-soluble contrast medium (WSCM). One hundred and sixty-four and 94
patients with normal thyroid function received HSG with OSCM and WSCM,
respectively. Approximately 25% of the women in the OSCM group developed
subclinical hypothyroidism (SCH), whereas only less than 10% of the patients in
the WSCM group developed SCH. Our data clearly indicate that WSCM is safe for
thyroid function in women who plan to get pregnant.
PMID- 28412870
TI - The effect of diabetes on ovaries in a rat model: the role of interleukin-33 and
apoptosis.
AB - Interleukin-33 (IL-33) is a novel cytokine involved in diabetes mellitus (DM) but
its role in diabetic ovarian injury is unknown. As IL-33 is modulated by
apoptosis, we aimed at investigating the effect of diabetes on ovaries in terms
of evaluating apoptosis and IL-33 in a rat model. In this prospective
experimental study, 16 female, nonpregnant Sprague-Dawley albino rats (12 weeks,
220-240 g) were randomly divided into two groups. Group 1 included eight healthy
nondiabetic rats as controls and group 2 included eight rats in which diabetes
was induced by intraperitoneal (i.p) injection of streptozotocin (STZ). After
overt DM occurred (blood glucose >400 mgr/dl), all animals were euthanized and
blood samples were collected by cardiac puncture for biochemical analysis.
Bilateral oophorectomy was performed for histopathological examination. Serum
levels of IL-33 and ovarian IL-33 and caspase-3 immunoexpressions were assessed.
Immunoexpressions of caspase-3 and IL-33 were significantly higher in ovarian
stromal cells of the diabetic rats compared to the controls. Also, in diabetic
group, serum IL33 levels were significantly higher than the control group. In
conclusion, increased IL-33 was observed both in serum and ovaries of STZ-induced
diabetic rats as well as increased apoptosis in these diabetic rats. IL-33 may
contribute to the apoptosis in diabetic ovarian injury.
PMID- 28412872
TI - Chinese Xibe population genetic composition according to linkage groups of X
chromosomal STRs: population genetic variability and interpopulation comparisons.
AB - BACKGROUND: The Xibe population is one of China's officially recognised
populations and is now distributed separately from west to east in the northern
part of China. X-chromosomal short tandem repeats have a special inheritance
pattern, and could be used as complements in forensic application, especially for
complex or deficiency cases. SUBJECTS AND METHODS: This study obtained the
allelic and haplotypic frequencies of 19 X-STR loci in the Xibe population from
Xinjiang Uygur Autonomous Region, China, and studied the genetic differentiations
between the Xibe and other populations. RESULTS: The combined power of
discrimination in females and males and mean exclusion chances in deficiency
cases, normal trios and duo cases was at least 0.999 999 994. In the haplotypic
study, the Xibe population showed a more similar pattern of haplotype
distribution with Asian populations than populations from other continents, while
allelic study also indicated a closer relationship between the Xibe and Asian
populations. CONCLUSIONS: The 19 X-STR loci would be useful in forensic
application in the studied population. The Xibe population showed a closer
genetic relationship with Asian populations in the study, and more population
data would be necessary for more detailed genetic relationship studies.
PMID- 28412873
TI - beta3-Adrenergic receptors, adipokines and neuroendocrine activation during
stress induced by repeated immune challenge in male and female rats.
AB - The main hypothesis of the study is that stress associated with repeated immune
challenge has an impact on beta3-adrenergic receptor gene expression in the
brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses
of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was
associated with body weight loss and increased anxiety-like behavior. In LPS
treated animals of both sexes, beta3-receptor gene expression was increased in
the prefrontal cortex but not the hippocampus. LPS treatment decreased beta3
receptor gene expression in white adipose tissue with higher values in males
compared to females. In the adipose tissue, LPS reduced peroxisome proliferator
activated receptor-gamma, leptin and adiponectin gene expression, but increased
interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted
in increased concentrations of plasma aldosterone and corticosterone with higher
values of corticosterone in females compared to males. Concentrations of
dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels
in the frontal cortex were lower in the LPS-treated animals compared to the
controls. Thus, changes of DHEA levels in the brain take place irrespective of
the changes of this neurosteroid in plasma. We have provided the first evidence
on stress-induced increase in beta3-adrenergic receptor gene expression in the
brain. Greater reduction of beta3-adrenergic receptor expression in the adipose
tissue and of the body weight gain by repeated immune challenge in male than in
female rats suggests sex differences in the role of beta3-adrenergic receptors in
the metabolic functions. LPS-induced changes in adipose tissue regulatory factors
and hormone concentrations might be important for coping with chronic infections.
PMID- 28412874
TI - Effects of Regulatory Support Services on Institutional Review Board Turnaround
Times.
AB - We evaluated how regulatory support services provided by University of Illinois
at Chicago's Center for Clinical and Translational Science may reduce
Institutional Review Board (IRB) turnaround times. IRB applications were
categorized by receipt of any regulatory support and amount of support received.
Turnaround time included total turnaround time, time for IRB review, and time for
investigators to modify protocols. There were no differences in any turnaround
times for supported versus nonsupported applications. However, for supported
applications, those receiving more intensive support had total turnaround times
16.0 days ( SE 7.62, p < .05) faster than those receiving less intensive support.
Receiving higher regulatory support may be associated with faster approval of IRB
submissions.
PMID- 28412875
TI - Amino acid and acylcarnitine profiles in perinatal asphyxia: a case-control
study.
AB - OBJECTIVE: To estimate cord blood amino acid and acylcarnitine levels in term
newborns exposed to perinatal asphyxia. MATERIALS AND METHODS: We studied 45
asphyxiated term newborns (cases) and 20 gestational age-matched healthy newborns
(control). 16 cases developed HIE according to clinical scoring and amplitude
integrated electroencephalography. Asphyxiated cases were accordingly subdivided
into: HIE group (n = 16) and Asphyxia group (n = 29). Amino acid and
acylcarnitine levels were measured in cord blood dried spot samples from all
newborns using ultra-performance liquid chromatography-mass spectrometry (UPLC
MS). Data were analyzed using one-way ANOVA with post hoc test and MetaboAnalyst
2. RESULTS: Distinct metabolite alterations were detected in cases versus
control, in HIE versus Asphyxia, and in Survivors within HIE group (n = 6) versus
nonsurvivors (n = 10). Principal component analysis (PCA) and partial least
squares-discriminate analysis (PLS-DA) showed increased levels of methionine and
certain acylcarnitines, but reduced levels of ornithine, histidine, and arginine.
Metabolite set enrichment analysis (MSEA); compared to KEGG library metabolite
sets, identified some disorders with similar metabolomic derangements.
CONCLUSIONS: We report UPLC-MS detectable alterations of amino acids and
acylcarnitines in asphyxiated newborns at birth, that can serve as early
diagnostic bedside biomarkers for HIE and predictors for its short-term outcome,
and in the near future, as therapeutic targets.
PMID- 28412876
TI - Effect of breastfeeding on postpartum depressive symptoms among adolescent and
young adult mothers.
AB - PURPOSE: To describe the association between breastfeeding and postpartum
depressive symptoms among a sample of adolescent and young adult mothers and to
determine whether breastfeeding difficulty moderates this association. MATERIALS
AND METHODS: Data were derived from a prospective cohort of pregnant adolescent
and young adult females (ages 14-21) as they transitioned to parenthood. This
analysis uses data collected during pregnancy and at 6 months postpartum among
mothers (n = 137) who initiated breastfeeding. Multivariable linear regression
was used to adjust for prenatal depressive symptoms and other potential
confounders. RESULTS: Postpartum depressive symptoms were not significantly
associated with breastfeeding duration or breastfeeding at 6 months. Early
breastfeeding difficulty moderated the association between depressive symptoms
and breastfeeding at 6 months. Among young mothers who were still breastfeeding
at 6 months, those who reported no early breastfeeding difficulties had the
lowest depressive scores and those who reported much early breastfeeding
difficulty had the highest depressive scores at 6 months. CONCLUSIONS: Minimizing
challenges with breastfeeding may help improve postpartum mental health among
adolescent and young adult mothers. Health care providers should help young
pregnant women manage expectations about breastfeeding and ensure that they are
linked to appropriate professional breastfeeding support during the early
postpartum period.
PMID- 28412877
TI - Retrospective Time Perception in Korsakoff's Syndrome.
AB - The authors investigated retrospective timing in participants with Korsakoff's
syndrome. Patients were assessed on four retrospective tasks on which they were
instructed to read three-digit numbers aloud (15 seconds), fill connected squares
(30 seconds), decide whether words were abstract or concrete (45 seconds), or
read aloud a text about mushroom picking (60 seconds). Participants were not
aware of the task's timing until the end of the tasks, when they were asked to
estimate the elapsed time. Results revealed an underestimation of the elapsed
time in Korsakoff participants, suggesting that time is perceived to pass quickly
for these participants.
PMID- 28412878
TI - "Top-Down" Mu-Opioid System Function in Humans: Mu-Opioid Receptors in
Ventrolateral Prefrontal Cortex Mediate the Relationship Between Hedonic Tone and
Executive Function in Major Depressive Disorder.
AB - Cognitive dysfunction and anhedonia, the reduced ability to experience pleasure,
are commonly comorbid symptoms that are persistent following successful
resolution of negative affect in major depressive disorder (MDD). Little is known
about whether they share common etiology. In the present study, the relationship
between ventrolateral prefrontal cortex (VLPFC) activity, cognitive dysfunction
(i.e., executive dysfunction), and positive emotionality was investigated in
conjunction with mu-opioid neurotransmission in a sample of 39 MDD patients.
Results suggest that increased endogenous mu-opioid tone in the VLPFC mediates
the relationship between increased trait positive emotionality and more efficient
executive functioning.
PMID- 28412879
TI - Quantitative Analysis of Transnasal Anterior Skull Base Approach: Report of
Technology for Intraoperative Assessment of Instrument Motion.
AB - OBJECTIVE: To develop a method to measure intraoperative surgical instrument
motion. This model will be applicable to the study of surgical instrument
kinematics including surgical training, skill verification, and the development
of surgical warning systems that detect aberrant instrument motion that may
result in patient injury. DESIGN: We developed an algorithm to automate
derivation of surgical instrument kinematics in an endoscopic endonasal skull
base surgery model. Surgical instrument motion was recorded during a cadaveric
endoscopic transnasal approach to the pituitary using a navigation system
modified to record intraoperative time-stamped Euclidian coordinates and Euler
angles. Microdebrider tip coordinates and angles were referenced to the cadaver's
preoperative computed tomography scan allowing us to assess surgical instrument
kinematics over time. A representative cadaveric endoscopic endonasal approach to
the pituitary was performed to demonstrate feasibility of our algorithm for
deriving surgical instrument kinematics. CONCLUSIONS: Technical feasibility of
automatically measuring intraoperative surgical instrument motion and deriving
kinematics measurements was demonstrated using standard navigation equipment.
PMID- 28412880
TI - Comment Concerning Cherkasova et al. (2016), Efficacy of Cognitive Behavioral
Therapy with and without Medication for Adults with ADHD.
PMID- 28412882
TI - Effects of a behaviour management technique for nursing staff on behavioural
problems after acquired brain injury.
AB - The ABC method is a behaviour management technique for use by nurses. ABC refers
to the identification of Antecedent events, target Behaviours, and Consequent
events. In this longitudinal intervention study with double baseline measurements
we evaluated the effectiveness of the ABC method in patients with behavioural
problems after acquired brain injury. Fifty-six patients participated in this
study. Outcome was measured in terms of overall neuropsychiatric problem
behaviour, aggression, apathy and emotional burden experienced by nurses. A
process evaluation was performed to investigate usability and acceptability of
the method and identify factors that influenced effectiveness. Friedman's ANOVA
showed a small significant reduction over time in overall neuropsychiatric
problem behaviour and aggression. The reduction was most prominent between the
first baseline measurement and the post-implementation and follow-up
measurements, not between the second baseline measurement and the post
implementation or follow-up measurements. This first group study on the effects
of the ABC method could not prove this technique is effective for patients with
behavioural problems after acquired brain injury. Nurses indicated that the ABC
method was not fully implemented in their daily routines. This may have
influenced results and makes it yet premature to draw firm conclusions on the
effects of the ABC method.
PMID- 28412881
TI - Glutathione S-transferase A1 (GSTA1) as a marker of acetaminophen-induced
hepatocyte injury in vitro.
AB - Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers
are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1
(GSTA1) plays a significant role in the metabolism of APAP. Primary mouse
hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced
hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and
determine whether GSTA1 could be a prognostic marker in vitro. A significant
increase (p < .05) in GSTA1 in cell culture supernatant was detected at 6 h after
APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase
(AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
showed marked differences (p < .05) at 8 h after APAP exposure, 2 h later than
GSTA1. Furthermore, GSTA1 increased in a dose-dependent manner with APAP
treatment. GSTA1 increased significantly (p < .05) at a concentration of 5.0
mmol/L APAP, while the marked changes in ALT, AST and other indexes were
undetectable until the concentration of APAP reached 7.5 mmol/L. These results
suggest that increased GSTA1 can be more sensitive than ALT and other indexes as
a marker of APAP-induced hepatic injury, which provide novel diagnostic index for
APAP-induced hepatic injury and supply valuable information to further understand
the pathogenesis of liver damage.
PMID- 28412883
TI - Polyphenols of virgin coconut oil prevent pro-oxidant mediated cell death.
AB - Virgin coconut oil (VCO), extracted from the fresh coconut kernel, is a food
supplement enriched with medium chain saturated fatty acids and polyphenolic
antioxidants. It is reported to have several health benefits including lipid
lowering, antioxidant and anti-inflammatory activities. The pharmacological
benefits of VCO have been attributed to its polyphenol content (VCOP), the
mechanistic basis of which is less explored. Liquid chromatography/mass
spectroscopy (LC/MS) analysis of VCOP documented the presence of gallic acid,
ferulic acid (FA), quercetin, methyl catechin, dihydrokaempferol and myricetin
glycoside. Pre-treatment of VCOP at different concentrations (25-100 MUg/mL)
significantly reduced the H2O2 and 2,2'-azobis (2-amidinopropane) dihydrochloride
(AAPH) induced cell death in HCT-15 cells. Giving further insight to its
mechanistic basis, oxidative stress induced alterations in glutathione (GSH)
levels and activities of GR (Glutathione-Reductase), GPx (Glutathione
Peroxidase), GST (Glutathione-S-Transferase) and catalase (CAT) were restored to
near-normal by VCOP, concomitantly reducing lipid peroxidation. The efficacy of
VCOP was similar to that of Trolox and FA added in culture. The study thus
suggests that VCOP protects cells from pro-oxidant insults by modulating cellular
antioxidant status.
PMID- 28412884
TI - Horizontally rotating disc recirculated photoreactor with TiO2-P25 nanoparticles
immobilized onto a HDPE plate for photocatalytic removal of p-nitrophenol.
AB - In this study, a horizontally rotating disc recirculated (HRDR) photoreactor
equipped with two UV lamps (6 W) was designed and fabricated for photocatalytic
removal of p-nitrophenol (PNP). Photocatalyst (TiO2) nanoparticles were
immobilized onto a high-density polyethylene (HDPE) disc, and PNP containing
solution was allowed to flow (flow rate of 310 mL min-1) in radial direction
along the surface of the rotating disc illuminated with UV light. The efficiency
of direct photolysis and photocatalysis and the effect of rotating speed on the
removal of PNP were studied in the HRDR photoreactor. It was found that TiO2-P25
nanoparticles are needed for the effective removal of PNP and there was an
optimum rotating speed (450 rpm) for the efficient performance of the HRDR
photoreactor. Then effects of operational variables on the removal efficiency
were optimized using response surface methodology. The results showed that the
predicted values of removal efficiency are consistent with experimental results
with an R2 of 0.9656. Optimization results showed that maximum removal percent
(82.6%) was achieved in the HRDR photoreactor at the optimum operational
conditions. Finally, the reusability of the HRDR photoreactor was evaluated and
the results showed high reusability and stability without any significant
decrease in the photocatalytic removal efficiency.
PMID- 28412885
TI - Antenatal taurine supplementation in fetal rats with growth restriction improves
neural stem cell proliferation by inhibiting the activities of Rho family
factors.
AB - OBJECTIVE: To investigate whether antenatal taurine supplementation improves
neural stem cell proliferation in rats with fetal growth restriction (FGR)
through regulating the activity of Rho family factors. METHODS: FGR models were
established via food restriction throughout pregnancy. Pregnant rats were
randomly divided into the control group, the FGR group (given 40% of the normal
daily feeding in the control group), and the Taurine group (FGR model treated
with 300 mg/kg.d taurine from gestational day seven). Expression of fatty acid
binding protein-7 (FABP-7), Rho-associated coiled coil-forming protein kinase
(ROCK2), Ras homolog gene family member A (RhoA), and rac in the brains of
newborn rats was detected by reverse transcription-polymerase chain reaction (RT
PCR), immunohistochemistry (IHC), and Western blotting (WB). RESULTS: Relative
FABP7 mRNA levels, the optical density (OD) values of FABP7-positive cells and
the expression levels of the tested proteins all demonstrated that the number of
neural stem cells (NSCs) in brain tissue was lower in the FGR group than in the
control group but was significantly increased after antenatal taurine
supplementation (p < .05). Compared with the control group, the mRNA and protein
levels of RhoA and ROCK2 were higher in the FGR group but lower in the Taurine
group (p < .05). In contrast, the rac mRNA level was lower in the FGR group than
in the control group but was higher in the Taurine group (p < .05). CONCLUSIONS:
Taurine prenatal supplementation improved neural stem cell proliferation in rats
with FGR by inhibiting the activity of Rho family factors.
PMID- 28412886
TI - A Long-Term, Open-Label, Safety Study of Triple-Bead Mixed Amphetamine Salts
(SHP465) in Adults With ADHD.
AB - OBJECTIVE: The aim of this study was to evaluate the long-term safety of triple
bead mixed amphetamine salts (MAS) in adults with ADHD. METHOD: Adults meeting
Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV
TR) ADHD criteria and satisfying study criteria from one of two antecedent
studies were enrolled in this 52-week (dose titration, 4 weeks; dose maintenance,
11 months) open-label extension. The protocol included 12.5- to 75-mg triple-bead
MAS but was amended to a maximum of 50-mg triple-bead MAS. Safety evaluations
included treatment-emergent adverse events (TEAEs) and vital signs. Clinical
outcome measures included ADHD Rating Scale-IV (ADHD-RS-IV) total score changes.
RESULTS: Of 505 enrolled participants, 266 completed the study; the M +/- SD
daily dose during the study was 48.0 +/- 15.96 mg. The most frequent TEAEs were
insomnia (initial insomnia, insomnia, early morning awakening, middle insomnia;
38.2%), headache (25.7%), and dry mouth (20.2%). Study discontinuations were more
frequent with higher doses of triple-bead MAS (37.5-75 mg) than with lower doses
(12.5 and 25 mg). Blood pressure and pulse increases were observed at end-of
study. Mean ADHD-RS-IV total score decreases from antecedent study and open-label
baselines at end-of-study were -23.3 +/- 11.44 and -7.9 +/- 13.19, respectively.
CONCLUSION: Triple-bead MAS exhibited a long-term safety profile comparable with
previous reports and demonstrated evidence of continued symptom control for up to
12 months.
PMID- 28412887
TI - Preventing and De-escalating Aggressive Behavior Among Adult Psychiatric
Patients: A Systematic Review of the Evidence.
AB - OBJECTIVE: The project goal was to compare the effectiveness of strategies to
prevent and de-escalate aggressive behaviors among psychiatric patients in acute
care settings, including interventions for reducing use of seclusion and
restraint. METHODS: Relevant databases were systematically reviewed for
comparative studies of violence prevention and de-escalation strategies involving
adult psychiatric patients in acute care settings. Studies (trials and cohort
studies) were required to report on aggression or seclusion or restraint
outcomes. Both risk of bias, an indicator of quality of individual studies, and
strength of evidence (SOE) for each outcome were independently assessed by two
study personnel. RESULTS: Seventeen primary studies met inclusion criteria.
Evidence was limited for benefits and harms; information about characteristics
that might modify the interventions' effectiveness, such as race or ethnicity,
was especially limited. All but one study had a medium or high risk of bias and
thus presented worrisome limitations. For prevention, risk assessment reduced
both aggression and use of seclusion and restraint (low SOE), and multimodal
interventions reduced the use of seclusion and restraint (low SOE). SOE for all
other interventions, whether aimed at preventing or de-escalating aggression, and
for modifying characteristics was insufficient. CONCLUSIONS: Available evidence
about strategies for preventing and de-escalating aggressive behavior among
psychiatric patients is very limited. Two preventive strategies, risk assessment
and multimodal interventions consistent with the Six Core Strategies principles,
may effectively lower aggressive behavior and use of seclusion and restraint, but
more research is needed on how best to prevent and de-escalate aggressive
behavior in acute care settings.
PMID- 28412888
TI - Postdeployment Behavioral Health Screens and Linkage to the Veterans Health
Administration for Army Reserve Component Members.
AB - OBJECTIVE: Approximately three to six months after returning from deployment,
military service members complete the Post-Deployment Health Reassessment
(PDHRA), which includes screens for alcohol misuse, depression, and posttraumatic
stress disorder (PTSD). To determine whether Army Reserve Component (RC) members
(Army National Guard and Army Reserve) with positive screening scores on the
PDHRA receive needed care, the investigators examined the association between
positive scores and enrollment and utilization of care ("linkage") in the
Veterans Health Administration (VHA), as well as rescreening scores, diagnosis,
and behavioral treatment in VHA. METHODS: Mixed-effects regression models were
used to predict linkage to VHA within six months after RC members (N=73,164)
completed the PDHRA, with alcohol misuse, depression, and PTSD screen scores as
key independent variables. Regression models were stratified by gender and
National Guard versus Reserve status. Among those who linked to VHA (N=25,168),
screening scores and subsequent diagnosis and treatment in VHA were also
examined. RESULTS: Army RC members with positive PTSD and depression screening
scores were more likely than those with negative screens to link to VHA, and most
(54%-84%) received VHA treatment once diagnosed. Positive screens for alcohol
misuse were associated with linkage to VHA for men but not for women, and
treatment rates for alcohol use disorders were relatively low (0%-25%) for both
men and women diagnosed as having an alcohol use disorder. CONCLUSIONS: The
finding that Army RC members with greater indications of behavioral health
problems linked to VHA is encouraging. However, more outreach and treatment
engagement strategies could be directed to those with alcohol use disorder,
particularly women.
PMID- 28412889
TI - Diabetes Prevalence Among Racial-Ethnic Minority Group Members With Severe Mental
Illness Taking Antipsychotics: Double Jeopardy?
AB - OBJECTIVE: This study assessed differences in diabetes prevalence based on race
ethnicity among people with severe mental illnesses. METHODS: This retrospective
cohort study examined diabetes prevalence in 2009 among California Medicaid
enrollees with severe mental illness who were screened for diabetes (N=19,364).
Poisson regression assessed differences in diabetes prevalence by race-ethnicity.
The sample was standardized to the U.S. POPULATION: RESULTS: The overall
prevalence of diabetes was 32.0%. The adjusted prevalence for all minority groups
with severe mental illness, except for Asians, was significantly higher than for
whites (1.21-1.28 adjusted prevalence ratios). With inverse probability weighting
to reduce selection bias captured by measured factors, estimated prevalence of
diabetes among screened participants was 27.3%. CONCLUSIONS: The prevalence of
diabetes in minority groups with severe mental illness was significantly higher
than among whites with severe mental illness. Mental health administrators should
implement universal diabetes screening with specific outreach efforts targeting
minority populations with severe mental illness.
PMID- 28412890
TI - Three Problems With Current Digital Mental Health Research . . . and Three Things
We Can Do About Them.
AB - An increasingly large body of randomized controlled trials has demonstrated the
efficacy of mental health technologies, such as Web-based and mobile
interventions, to prevent and treat mental disorders and increase psychological
well-being. However, there is little evidence that these tools can be
successfully implemented in clinical settings. The authors highlight three widely
held misconceptions that they believe are holding back the field, and they
reconceptualize the issues to strengthen the path toward implementation and
accelerate innovation.
PMID- 28412891
TI - Service Receipt and Mental Disorders in Child Welfare and Mental Health Systems
in Los Angeles County.
AB - OBJECTIVE: Use of administrative data from child welfare (CW) and mental health
systems in Los Angeles County provided a unique opportunity to more closely
examine mental health needs of children dually served by these systems. This
study examined the presence of mental disorders and correlates of receipt of
mental health services by diagnostic classification in this population. METHODS:
Data were obtained for 3,191 children receiving services from Los Angeles
County's Department of Children and Family Services and Department of Mental
Health (DMH) between July 2011 and July 2012. Multivariate linear and logistic
regression models examined the relationship between sociodemographic and CW
related characteristics and receipt of outpatient services by clinician-diagnosed
mental disorder. RESULTS: Of the 3,191 referred children, 68% met criteria for
one of the four diagnostic classifications. Mood disorders were the most common
diagnosis (30%), followed by anxiety disorders (20%), behavior disorders (9%),
and attention-deficit hyperactivity disorder (9%). Children with prior DMH
involvement received more services regardless of diagnosis. Older children (ages
>=15) received more services than younger children, whereas younger children were
more likely to receive family therapy. Race-ethnicity did not play a significant
role in predicting service receipt. CONCLUSIONS: The unique mental health needs
of CW-involved children were exemplified by the differences found in the
percentages of children with diagnoses of mental disorders between this sample
and children in the general population. Because of family and placement
disruptions among CW-involved children, it is important that the provision of
individual therapy is not overlooked in favor of family therapy.
PMID- 28412893
TI - Public Attitudes and Feelings of Warmth Toward Women and Men Experiencing
Depression During the Perinatal Period.
AB - OBJECTIVE: Depression is a major public health concern and often goes untreated.
In response to a growing body of research documenting stigma as a barrier to
depression care, this study focused on examining public stigma toward potentially
vulnerable subpopulations. METHODS: Participants (N=241) were recruited from
Amazon's Mechanical Turk and randomly assigned to provide anonymous ratings on
attitudes and feelings of warmth toward pregnant women and expectant fathers
experiencing depression, mothers and fathers experiencing postpartum depression,
or women and men experiencing depression during nonperinatal periods. RESULTS:
Participants reported significantly more negative attitudes about depressed men
than women, and male participants reported significantly more negative attitudes
than female participants toward depressed individuals. Similarly, participants
felt significantly less warmth toward depressed men than women, and male
participants expressed significantly less warmth than female participants toward
depressed individuals. Male participants felt equally warm toward men and women
who experienced depression during nonperinatal periods, whereas female
participants felt significantly warmer toward women who experienced depression
during nonperinatal periods compared with men. CONCLUSIONS: Results indicate that
the public views depressed men more negatively than depressed women and that
males are more likely to hold stigmatizing attitudes toward depression,
suggesting the importance of reducing stigma directed toward men with depression
and stigma held by men toward persons with depression. Attitudes and feelings
toward depressed individuals did not consistently vary by perinatal status. These
findings are an initial step in improving depression treatment engagement
strategies and in identifying those who would benefit most from stigma reduction
programs.
PMID- 28412892
TI - Is There a Role for Fidelity Self-Assessment in the Individual Placement and
Support Model of Supported Employment?
AB - OBJECTIVE: Fidelity assessments help ensure that evidence-based practices are
implemented properly. Although assessments are typically conducted by independent
raters, some programs have implemented self-assessments because of resource
constraints. Self-assessments were compared with independent assessments of
programs implementing individual placement and support supported employment.
METHODS: Eleven community-based outpatient programs in New York State completed
both self- and independent assessments. Intraclass correlation coefficients and
paired t tests were used to compare scores from self- and independent
assessments. RESULTS: For both assessment methods, mean scores for all programs
were within the range of fair fidelity. Self- and independent assessment total
scores were not significantly different; however, significant differences were
found on some scale items in this small sample. CONCLUSIONS: Self-assessment may
be valid for examining a program's overall functioning and useful when resource
constraints prevent independent assessment. Independent assessors may be able to
identify nuances, particularly on individual assessment items, that can point to
areas for program improvement.
PMID- 28412894
TI - Mental Health Treatment Seeking Among Veteran and Civilian Community College
Students.
AB - OBJECTIVE: A Web-based survey examined treatment seeking among community college
students to inform the design of engagement interventions. METHODS: Veteran and
civilian community college students (N=765) were screened for mental disorders
and reported perceptions of treatment need, effectiveness, and stigma, as well as
service use. Regression analysis identified predictors of pharmacotherapy and
psychotherapy use. RESULTS: Of the 511 students who screened positive for a
current mental disorder or reported a perceived need for treatment (149 veterans
and 362 civilians), 30% reported past-year use of psychotropic medications.
Predictors were perceived treatment need (odds ratio [OR]=7.81, p<.001) and the
perception that psychotropic medications are effective (OR=3.38, p=.012). Eleven
percent of participants reported past-year psychotherapy use, and predictors were
a positive screen for posttraumatic stress disorder (OR=2.78, p=.04) and poorer
financial status. CONCLUSIONS: Modifiable barriers, including perceived need for
and effectiveness of treatment, were correlated with pharmacotherapy use and
should be targeted by engagement interventions.
PMID- 28412895
TI - Self-Stigma and Consumer Participation in Shared Decision Making in Mental Health
Services.
AB - OBJECTIVE: People with mental illness struggle with symptoms and with public
stigma. Some accept common prejudices and lose self-esteem, resulting in shame
and self-stigma, which may affect their interactions with mental health
professionals. This study explored whether self-stigma and shame are associated
with consumers' preferences for participation in medical decision making and
their behavior in psychiatric consultations. METHODS: In a cross-sectional study
conducted in Germany, 329 individuals with a diagnosis of a schizophrenia
spectrum disorder or an affective disorder and their psychiatrists provided
sociodemographic and illness-related information. Self-stigma, shame, locus of
control, and views about clinical decision making were assessed by self-report.
Psychiatrists rated their impression of the decision-making behavior of
consumers. Regression analyses and structural equation modeling were used to
determine the association of self-stigma and shame with clinical decision making.
RESULTS: Self-stigma was not related to consumers' participation preferences, but
it was associated with some aspects of communicative behavior. Active and
critical behavior (for example, expressing views, daring to challenge the
doctor's opinion, and openly speaking out about disagreements with the doctor)
was associated with less shame, less self-stigma, more self-responsibility, less
attribution of external control to powerful others, and more years of education.
CONCLUSIONS: Self-stigma and shame were associated with less participative and
critical behavior, which probably leads to clinical encounters that involve less
shared decision making and more paternalistic decision making. Paternalistic
decision making may reinforce self-stigma and lead to poorer health outcomes.
Therefore, interventions that reduce self-stigma and increase consumers' critical
and participative communication may improve health outcomes.
PMID- 28412896
TI - Disparities in Health Care Utilization and Functional Limitations Among Adults
With Serious Psychological Distress, 2006-2014.
AB - OBJECTIVE: This study compared health care access, utilization, and functional
indicators among adults with and without serious psychological distress (SPD) in
the years surrounding implementation of the Patient Protection and Affordable
Care Act (ACA). METHODS: Adults ages 18 to 64 from the 2006-2014 National Health
Interview Survey (N=207, 853) were examined on 11 access, utilization, and
functional indicators: health insurance coverage (health coverage), insufficient
money for medications, delay in health care (delay in care), insufficient money
for health care, visiting a doctor ten or more times in the past 12 months,
change in place of health care, change in place of health care due to insurance,
limitations in ability to work, limitations in activities of daily living (ADLs),
insufficient money for mental health care, and having seen a mental health care
provider. RESULTS: Multivariate models that were adjusted for health coverage and
sociodemographic characteristics indicated that compared with adults without SPD,
adults with SPD had greater odds of lacking money for medications (AOR=10.0) and
health care (AOR=3.1), experiencing delays in care (AOR=2.7), visiting a doctor
ten or more times in the past 12 months (AOR=3.2), changing usual place of health
care (AOR=1.5), changing usual place of health care because of insurance
(AOR=1.5), and experiencing limitations in ADLs (AOR=3.6) and ability to work
(AOR=1.8). The proportions of adults with SPD who lacked health coverage and
money to buy prescriptions increased during the study period. Although this trend
reversed in 2014, the proportion with SPD experiencing barriers remained above
2006 levels. CONCLUSIONS: Health care patterns among adults with SPD require
greater attention.
PMID- 28412897
TI - Rates of Cervical Cancer Screening Among Women With Severe Mental Illness in the
Public Health System.
AB - OBJECTIVE: This study aimed to determine cervical cancer screening rates among
women with severe mental illness. METHODS: California Medicaid administrative
records (2010-2011) for 31,308 women with severe mental illness were examined.
Participants received specialty mental health services and were not dually
eligible for Medicare. Poisson models assessed association between selected
predictors and cervical cancer screening. RESULTS: Overall, 20.2% of women with
severe mental illness received cervical cancer screening during the one-year
period. Compared with white women, Asian women (adjusted risk ratio [ARR]=1.23),
black women (ARR=1.10), and Hispanic women (ARR=1.11) (p<.001) were more likely
to have been screened. Women ages 28-37 were more likely than those ages 18-27 to
have been screened (ARR=1.31, p<.001). Evidence of other health care use was the
strongest predictor of screening (ARR=3.07, p<.001). CONCLUSIONS: Most women in
the sample were not regularly screened for cervical cancer. Cervical cancer
screening for this high-risk population should be prioritized.
PMID- 28412898
TI - A Collaborative Process for Evaluating Infant Mental Health Home Visiting in
Michigan.
AB - This column describes an innovative collaboration in Michigan that could serve as
a model for meaningful community-university-state partnerships. Recent
legislation in Michigan threatened the infant mental health home visiting
program, a service for Medicaid-eligible infants, toddlers, and families affected
by mental illness. The University of Michigan is overseeing two major studies in
collaboration with the Michigan Department of Health and Human Services, the
Michigan Association for Infant Mental Health, the Michigan Infant Toddler
Research Exchange faculty network, and community health service providers to
determine the evidence base for the program and ensure its future success.
PMID- 28412899
TI - Monitoring of Patients on Second-Generation Antipsychotics: A National Survey of
Child Psychiatrists.
AB - OBJECTIVE: The survey assessed self-reported monitoring by child psychiatrists of
children prescribed second-generation antipsychotics, facilitators and barriers
to monitoring, and steps taken to adhere to monitoring. METHODS: The authors
anonymously surveyed 4,144 U.S. child psychiatrists. Descriptive statistics and
multiple linear regressions were utilized to describe results and identify
correlates of monitoring. RESULTS: Among responders (N=1,314, 32%), over 95% were
aware of all guidelines, over 80% agreed with most guidelines, but less than 20%
had adopted and adhered to most guidelines. Awareness of guidelines, working
within an academic practice, and fewer years in practice predicted adherence.
CONCLUSIONS: Child psychiatrists have generally not adopted the guidelines for
monitoring children on second-generation antipsychotics. Interventions to improve
monitoring should target child psychiatrists in nonacademic practices and those
who have been out of training for longer periods. Future research should assess
family barriers to monitoring.
PMID- 28412900
TI - Reducing Behavioral Health Inpatient Readmissions for People With Substance Use
Disorders: Do Follow-Up Services Matter?
AB - OBJECTIVE: Individuals with substance use disorders are at high risk of hospital
readmission. This study examined whether follow-up services received within 14
days of discharge from an inpatient hospital stay or residential detoxification
reduced 90-day readmissions among Medicaid enrollees whose index admission
included a substance use disorder diagnosis. METHODS: Claims data were analyzed
for Medicaid enrollees ages 18-64 with a substance use disorder diagnosis coded
in any position for an inpatient hospital stay or residential detoxification in
2008 (N=30,439). Follow-up behavioral health services included residential,
intensive outpatient, outpatient, and medication-assisted treatment (MAT).
Analyses included data from ten states or fewer, based on a minimum number of
index admissions and the availability of follow-up services or MAT. Survival
analyses with time-varying independent variables were used to test the
association of receipt of follow-up services and MAT with behavioral health
readmissions. RESULTS: Two-thirds (67.7%) of these enrollees received no follow
up services within 14 days. Twenty-nine percent were admitted with a primary
behavioral health diagnosis within 90 days of discharge. Survival analyses showed
that MAT and residential treatment were associated with reduced risk of 90-day
behavioral health admission. Receipt of outpatient treatment was associated with
increased readmission risk, and, in only one model, receipt of intensive
outpatient services was also associated with increased risk. CONCLUSIONS:
Provision of MAT or residential treatment for substance use disorders after an
inpatient or detoxification stay may help prevent readmissions. Medicaid programs
should be encouraged to reduce barriers to MAT and residential treatment in order
to prevent behavioral health admissions.
PMID- 28412901
TI - An Analysis of Central Residues Between Ligand-Bound and Ligand-Free Protein
Structures Based on Network Approach.
AB - BACKGROUND: Depiction of protein structures as networks of interacting residues
has enabled us to understand the structure and function of the protein. Previous
investigations on closeness centrality have identified protein functional sites
from three- dimensional structures. It is well recognized that ligand binding to
a receptor protein induces a wide range of structural changes. OBJECTIVE: An
interesting question is how central residues function during conformational
changes triggered during ligand binding? The aim of this study is to comprehend
at what extent central residues change during ligand binding to receptor
proteins. METHOD: To determine this, we examined 37 pairs of protein structures
consisting of ligand-bound and ligand-free forms. These protein structures were
modelled as an undirected network and significant central residues were obtained
using residue centrality measures. In addition to these, the basic network
parameters were also analysed. RESULTS: On analysing the residue centrality
measures, we observed that 60% of central residues were common in both the ligand
bound and ligand-free states. The geometry of the central residues revealed that
they were situated closer to the protein center of the mass. Finally, we
demonstrated the effectiveness of central residues in amino acids substitutions
and in the evolution itself. The closeness centrality was also analyzed among
different protein domain sizes and the values gradually declined from single
domains to multi-domain proteins suggesting that the network has potential for
hierarchical organization. Betweenness centrality measure was also used to
determine the central residues and 31% of these residues were common between the
holo/apo states. CONCLUSION: Findings reveal that central residues play a
significant role in determining the functional properties of proteins. These
results have implications in predicting binding/active site residues,
specifically in the context of drug designing, if additional information
concerning ligand binding is exploited.
PMID- 28412902
TI - Nanosafety: Towards Safer Nanoparticles by Design.
AB - The continuous development of Nanotechnology is progressively introducing
nanoparticles into society. However, little is known about the safety of
nanoparticles and functions of engineered nanomaterials, in particular how the
physicochemical properties of the materials relate to mechanisms of injury at the
nano-bio interface. While comprehensive knowledge on the potential toxicity of
NPs is still lacking, as time goes by and research in the field continues,
different aspects, such as interactions with the immune system, perturbation of
cellular membranes, transportation of toxic moieties and others are emerging as
potentially hazardous aspects of NPs. As a result, this rapidly advancing new
field requires the development of novel test strategies based on the contribution
of toxicological pathways to the pathophysiology of disease that allow complex
toxicants to be screened in robust, mechanism-based assays in which the bulk of
the investigation can be carried out at the cellular and biomolecular level
whilst maintaining limited animal use. A review of these strategies will help to
provide guidelines for synthetic nanochemists on how to design NPs to be safe
during their full life cycle while maintaining their parental desired properties.
PMID- 28412903
TI - Phage Life Cycles Behind Bacterial Biodiversity.
AB - Bacteriophages (phages or bacterial viruses) are the most abundant biological
entities in our planet; their influence reaches far beyond the microorganisms
they parasitize. Phages are present in every environment and shape up every
bacterial population in both active and passive ways. They participate in the
circulation of organic matter and drive the evolution of microorganisms by
horizontal gene transfer at unprecedented scales. The mass flow of genetic
information in the microbial world influences the biosphere and poses challenges
for science and medicine. The genetic flow, however, depends on the fate of the
viral DNA injected into the bacterial cell. The archetypal notion of phages only
engaging in predatorprey relationships is slowly fading. Because of their varied
development cycles, environmental conditions, and the diversity of microorganisms
they parasitize, phages form a dense and highly complex web of dependencies,
which has important consequences for life on Earth. The sophisticated phage
bacteria interplay includes both aggressive action (bacterial lysis) and
"diplomatic negotiations" (prophage domestication). Here, we review the most
important mechanisms of interactions between phages and bacteria and their
evolutionary consequences influencing their biodiversity.
PMID- 28412904
TI - The Role of Exosomes and Exosome-derived microRNAs in Atherosclerosis.
AB - BACKGROUND: Atherosclerosis is the leading cause of death and morbidity
throughout industrialized nations, accounting for one-fifth of all deaths
globally. Exosomes are bi-lipid membranous vesicles containing protein, lipid and
nucleic acid contents that are released from the cells via the endolysosomal
pathway. Exosomes are derived from several cells including macrophages, dendritic
cells, platelets as well as human serum. METHODS: In this review, an overview of
recent advances, the evidence for the role of exosomes and exosomederived
microRNAs (miRNAs) in atherosclerosis are provided. RESULTS: Recent evidence has
shown that exosomes derived from the cells mentioned above are involved in
atherosclerosis, whose secretion appears to be regulated by various natural and
experimental stimuli, physiological and pathological processes. CONCLUSION:
Exosomes are now accepted as specifically secreted vesicles that enable
intercellular communications and have become exponentially interesting to be used
as the possible relevant biomarkers in disease development such as cadiovascular
disease, particular in atherosclerosis in addition to their minimally invasive
clinical diagnosis.
PMID- 28412905
TI - Therapeutic Potential of Heme Oxygenase-1/carbon Monoxide System Against Ischemia
Reperfusion Injury.
AB - BACKGROUND: Ischemia-reperfusion (I/R) injury causes the dysfunctions of
different major organs, leading to morbidity and mortality on the global scale.
Among a battery of therapeutic targets, the heme oxygenase- 1 (HO-1)/carbon
monoxide (CO) system has been evaluated for the development of new therapies
against I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three
biologically active end products, namely biliverdin/bilirubin, CO and ferrous
ion. Interestingly, CO is one of a few bioactive gaseous molecules with the
capability of regulating inflammation, cell survival and growth. In fact, several
CO-releasing compounds have been developed for directly reprogramming the
intracellular apoptotic, inflammatory and proliferative signaling networks. In
parallel, chemical and genetic approaches have also been evaluated for up
regulating HO-1 expression as an endogenous mechanism to ameliorate I/R injury
and heal wounds. METHODS: In this review, we discussed the recent studies on the
therapeutic potential of HO-1/CO system in the treatment of I/R injury in the
heart, brain, liver, kidney, lung, intestine and retina. We focused on the
activities and underlying mechanisms of various therapeutic strategies to
regulate HO-1/CO system against I/R injury. RESULTS: A large number of studies
have demonstrated that HO-1/CO system exhibits potent anti-oxidative,
antiapoptotic, anti-inflammatory and cytoprotective activities against I/R
injury. The regulation of HO-1/CO expression has been achieved either by genetic
overexpression of HO-1 cDNA or pharmacological induction with drugs including
curcumin and resveratrol. CONCLUSION: The HO-1/CO system is a potential target
for treating I/R injury. Further studies should be directed to in vivo efficacy
and clinical application of HO-1/CO system in the therapy of I/R injury.
PMID- 28412906
TI - Combined Approach of QSAR and Docking Studies for the Design of Local Anaesthetic
Agents.
AB - BACKGROUND: Heterocyclic scaffold, benzotriazole and its derivatives are
potential anaesthetic agents that act locally. OBJECTIVE: QSAR and docking
analysis of previously synthesized benzotriazolyl derivatives were modelled for
their local anaesthetic action using computer assisted multiple regression
analysis. It provides the insight about the structural requirements for the local
anaesthetic action. METHOD: A training set comprising of 16 molecules and test
set of 8 molecules were selected for present investigation by using sphere
exclusion method with dissimilarity value of +4.0. The validation of the QSAR
models was performed by cross-validation and external test set prediction.
Docking studies was performed using GRIP docking methodology. RESULTS &
CONCLUSION: Further GRIP docking with the pentameric ligand gated ion channel,
2XQ3 facilitated the mechanistic analysis of interactions of the test molecules
active site residues.
PMID- 28412907
TI - Review of the Pharmacology of the Emerging Possibilities of the Direct Oral
Anticoagulants' Reversal.
AB - BACKGROUND: Direct oral anticoagulants (DOACs) offer consistent and predictable
anticoagulation, oral administration with good patient compliance and a good
safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and
rivaroxaban - direct factor Xa inhibitors are now largely used for
anticoagulation in patients with nonvalvular atrial fibrillation and in patients
with venous thromboembolism. These agents have emerged as an expediential
clinical choice in long-term anticoagulation for an increasing number of
patients. Despite their advantages, concerns persist about a lack of rapid
reversal agents in urgent clinical situations. METHODS: This review is focused on
the pharmacology of nonspecific and target-specific reversal agents for DOACs
induced anticoagulation. A systemic review of preclinical and clinical studies
published in peer-reviewed scientific journals was performed. RESULTS AND
CONCLUSIONS: Fresh frozen plasma and coagulation factors concentrates might be
considered in bleeding emergencies; however, there is a lack of larger studies
confirming the efficacy of coagulation factors concentrates for the reversal of
DOACs-induced anticoagulation, and a particular risk of coagulation factors
concentrates-induced thrombosis. Recently, idarucizumab has been approved
commercially for acute reversal of dabigatran in emergencies as a first target
specific reversal agent. Moreover, andexanet alpha and aripazine are being
extensively studied in several phase II and III clinical studies. It is likely
that more target-specific agents for reversal of DOACs-induced anticoagulation
will be introduced to clinical practice in near future.
PMID- 28412908
TI - News in the Indications of Direct Oral Anticoagulants According to the American
College of Chest Physicians 2016 Guidelines.
AB - BACKGROUND: The 10th edition of the CHEST Guideline and Expert Panel Report for
the treatment of venous thromboembolism (VTE) was recently updated with
recommendations on both the choice of anticoagulants and the duration of
treatment in diverse clinical scenarios. METHOD: In this paper, we focus on news
in the use of direct oral anticoagulants (DOACS), a group of synthetic low
molecular weight drugs capable of directly and specifically inhibiting either
activated factor X or both free and fibrin- bound thrombin. RESULTS: New to the
guidelines is the recommendation of the use of DOACS over vitamin K-antagonists
(VKA's) in individuals without cancer who develop VTE. The choice and intensity
of anticoagulants is the same for lower and upper extremity thrombosis or for
pulmonary embolism. For cancer-related thrombosis low molecular weight heparin is
still recommended over the use of VKA's or DOACS, though high quality evidence
for this choice is lacking. If therapy is given beyond three months, remaining on
the same anticoagulant is suggested. Re-thrombosis while on regular use of DOACs
requires switching to low molecular weight heparins at least for one month.
CONCLUSION: Ultimately the choice of anticoagulant will depend on patient
specific factors such as comorbidities, compliance, patient preferences,
availability and costs. We address the news in DOAC use in VTE from the
perspective of an upper-middle income economy.
PMID- 28412909
TI - Prolonged Perfusion Predicts Recurrent Ischemic Stroke but not Transient Ischemic
Attack in Patients with Symptomatic Intracranial Stenosis.
AB - BACKGROUND: Intracranial arterial stenosis (ICAS) is the dominant cause for
ischemic stroke worldwide, with hemodynamic compromise as a crucial contributor.
Prolonged perfusion is commonly observed in ICAS patients on CT perfusion (CTP)
maps, while the clinical significance of this perfusion pattern has not been
elucidated. METHOD: Patients having symptomatic ICAS of 50-99% stenosis with
sustained downstream cerebral blood flow (CBF) were enrolled in this study.
Prolonged perfusion was defined as increased mean transit time (MTT) in vascular
territories of the target ICAS on CTP maps. The primary clinical outcome was
recurrence of ipsilateral ischemic stroke, and secondary outcome was any
ipsilateral ischemic events at 2 years follow-up. RESULTS: Of the 95 patients
(median age 61y; 70% males) with symptomatic ICAS, 29 patients (30.5%) had
prolonged perfusion. Such delayed perfusion was persistent in a majority of
patients according to the 1-year imaging follow-up. The prolongation of cerebral
perfusion was associated with subsequent risk for ipsilateral ischemic stroke (HR
7.01; 95% CI 1.86-26.46; p = 0.004), but not for any ipsilateral ischemic events
(HR 1.52; 95% CI 0.63-3.68; p = 0.348). Further comparison of perfusion measures
showed lower CBF (p = 0.034) and higher MTT (p = 0.064) in patients with
recurrent ischemic stroke, but not in those with recurrent transient ischemic
attack (TIA). Among patients with recurrent stroke, a majority had multiple
infarcts along the borderzone regions. CONCLUSION: In patients with symptomatic
ICAS, persistent prolonged cerebral perfusion might contribute to the relapse of
ischemic stroke, but not TIA.
PMID- 28412911
TI - Pharmacological Therapy of Abdominal Aortic Aneurysm: An Update.
AB - BACKGROUND: Abdominal aortic aneurysm (AAA), a progressive segmental abdominal
aortic dilation, is associated with high mortality. AAA is characterized by
inflammation, smooth muscle cell (SMC) depletion and extracellular matrix (ECM)
degradation. Surgical intervention and endovascular therapy are recommended to
prevent rupture of large AAAs. Unfortunately, there is no reliable
pharmacological agent available to limit AAA expansion. In the past decades,
extensive investigations and a body of ongoing clinical trials aimed at defining
potent treatments to inhibit and even regress AAA growth. CONCLUSION: In this
review, we summarized recent progress of potential strategies, particularly
macrolides, tetracyclines, statins, angiotensin converting enzyme inhibitors,
angiotensin receptor blocker, corticosteroid, anti-platelet drugs and mast cell
stabilizers. We also consider recently identified novel molecular targets, which
have potential to be translated into clinical practice in the future.
PMID- 28412912
TI - The Socioeconomic Effects of Uncontrolled Hypertension.
AB - BACKGROUND: Hypertension (HT), albeit a modifiable risk factor of cardiovascular
morbidity and mortality, remains one of the main contributors to the total
disease burden internationally and, thus, inevitably one of the basic cost
drivers in healthcare systems. CONCLUSION: Taking the above into account, this
brief narrative review aims at presenting the main findings of the international
health economics literature on HT with regards to four key areas: a) the costs
attributable to HT, b) the effects of HT on patient well-being, c) the cost
effectiveness of pharmaceutical interventions against high blood pressure, and,
d) the costs and benefits of preventive measures against HT. Bearing in mind the
available evidence on disease costs and the efficiency of interventions, HT must
constitute a primary objective of modern health policy, internationally.
PMID- 28412913
TI - Anti-Carcinogenic Effects of Carnosol-An Updated Review.
AB - BACKGROUND: Despite the newly treatment procedures, cancer is considered as the
main health threat nowadays and, therefore, new therapeutic options such as
traditional medicine should be investigated. Rosemary (Rosmarinus officinalis L.)
has been found to possess antitumor effects due to its major ingredients,
including carnosic acid, carnosol, ursolic acid, and rosmarinic acid. OBJECTIVE:
This study was designed to gather the recent literature findings from 2010 to
2016 on the cancer anti-tumor activities of carnosol and probably involved
mechanisms. METHOD: The online English papers were gathered through various
search websites, including PubMed, Iran Medex, Medline, Google Scholar, and
Scopus from 2010 to 2016. RESULTS: Carnosol, the specific composition of
rosemary, has been shown to have beneficial effects in keeping humans healthy and
may be acted as an antitumor agent. CONCLUSION: This review revealed that
carnosol may be effective as an anti-tumor agent in the different types of cancer
by inducing apoptosis and inhibiting the cell cycle division. However, more
studies are needed to confirm carnosol therapeutic effects in human.
PMID- 28412910
TI - Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity.
AB - BACKGROUND: The treatment of schizophrenia is challenging due to the wide range
of symptoms (positive, negative, cognitive) associated with the disease. Typical
antipsychotics that antagonize D2 receptors are effective in treating positive
symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical
antipsychotics targeting 5-HT2A and D2 receptors are more effective at treating
cognitive and negative symptoms compared to typical antipsychotics, but these
drugs also result in side-effects such as metabolic syndromes. OBJECTIVE: To
identify evidence in the literature that elucidates the pharmacological profile
of aripiprazole.s. METHODS: We searched PubMed for peer reviewed articles on
aripiprazole and its clinical efficacy, side-effects, pharmacology, and effects
in animal models of schizophrenia symptoms. RESULTS: Aripiprazole is a newer
atypical antipsychotic that displays a unique pharmacological profile, including
partial D2 agonism and functionally selective properties. Aripiprazole is
effective at treating the positive symptoms of schizophrenia and has the
potential to treat negative and cognitive symptoms at least as well as other
atypical antipsychotics. The drug has a favorable side-effect profile and has a
low propensity to result in EPS or metabolic syndromes. Animal models of
schizophrenia have been used to determine the efficacy of aripiprazole in symptom
management. In these instances, aripiprazole resulted in the reversal of deficits
in extinction, pre-pulse inhibition, and social withdrawal. Because aripiprazole
requires a greater than 90% occupancy rate at D2 receptors to be clinically
active and does not produce EPS, this suggests a functionally selective effect on
intracellular signaling pathways. CONCLUSION: A combination of factors such as
dopamine system stabilization via partial agonism, functional selectivity at D2
receptors, and serotonin-dopamine system interaction may contribute to the
ability of aripiprazole to successfully manage schizophrenia symptoms. This
review examines these mechanisms of action to further clarify the pharmacological
actions of aripiprazole.
PMID- 28412915
TI - Early Functional and Structural Microvascular Changes in Hypertension Related to
Aging.
AB - It is becoming increasingly clear that both microvascular network alterations and
subsequent tissue perfusion defects may precede and predict the development of
arterial hypertension and other cardiovascular and metabolic diseases, including
diabetes and metabolic syndrome. Moreover, the subsequent functional and
structural alterations in microvascular reactivity and density, as well as
alterations in the macrocirculation characteristic of physiologic vascular aging,
contribute to the development of target organ damage. Microvascular rarefaction
appears to be an early vascular structural alteration in the setting of
hypertension, as it is already present in individuals presenting with borderline
hypertension and normotensive young adults with a familial predisposition to high
blood pressure. The chronic increases in blood pressure that occur during
senescence secondary to macrocirculatory changes induce vasoconstriction within
the microcirculation, which promotes the development of tissue hypoxia and
reduces both arteriolar and capillary density. This phenomenon contributes to
additional increases in peripheral vascular resistance and establishes a vicious
cycle that culminates in both tissue injury and target organ damage, which are
equally present in senescence and hypertension. Therefore, the microcirculation
may be considered an essential target for both the pharmacological and non
pharmacological treatment of arterial hypertension and other cardiovascular
diseases.
PMID- 28412914
TI - Early Vascular Ageing (EVA): Definitions and Clinical Applicability.
AB - Arterial stiffness has been accumulating evidence as an intermediate
cardiovascular endpoint. It has been established as an independent risk marker
for cardiovascular disease, and reflects the dissociation between chronologic and
biologic age of large arteries-attributing earlier the risk that a normal
vascular ageing process had installed to occur several years later. The concept
of Early Vascular Ageing (EVA) is developed to establish primordial prevention,
identifying individuals whose ageing path has been accelerated either by inherent
features, interaction with the environment or arterial exposure to several types
of insults that evolve to medial layer morphological changes. Understanding the
pathophysiology of vascular ageing, its consequences and therapeutic
opportunities is therefore an advantage that could be translated in time of
prevention and survival free of cardiovascular disease. As the EVA construct is
advancing, new features appear as interesting to better translate it into
clinical practice.
PMID- 28412916
TI - Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An
Update.
AB - BACKGROUND: Cannabis is the illicit drug with both the largest current levels of
consumption and the highest reported lifetime prevalence levels in the world.
Across different countries, the prevalence of cannabis use varies according to
the individual income, with the highest use being reported in North America,
Australia and Europe. Despite its 'soft drug' reputation, cannabis misuse may be
associated with several acute and chronic adverse effects. OBJECTIVE: The present
article aims at reviewing several papers on epidemiological, neurobiological and
psychopathological aspects of the use of cannabis. The PubMed database was here
examined in order to collect and discuss a range of identified papers.
DISCUSSION: Cannabis intake usually starts during late adolescence/early
adulthood (15-24 years) and drastically decreases in adulthood with the
acquisition of working, familiar and social responsibilities. Clinical evidence
supports the current socio-epidemiological alarm concerning the increased
consumption among youngsters and the risks related to the onset of psychotic
disorders. The mechanism of action of cannabis presents some analogies with other
abused drugs, e.g. opiates. Furthermore, it has been well demonstrated that
cannabis intake in adolescence may facilitate the transition to the use and/or
abuse of other psychotropic drugs, hence properly being considered a 'gateway
drug'. Some considerations on synthetic cannabimimetics are provided here as
well. CONCLUSION: In conclusion, the highest prevalence of cannabis use and the
social perception of a relatively low associated risk are in contrast with
current knowledge based on biological and clinical evidence. Indeed, there are
concerns relating to cannabis intake association with detrimental effects on both
cognitive impairment and mental health.
PMID- 28412917
TI - Is there a Teratogenicity Risk Associated with Cannabis and Synthetic
Cannabimimetics' ('Spice') Intake?
AB - BACKGROUND: Substance use, including cannabis, has been documented amongst women
both in the pre-conception period and during pregnancy, particularly during the
1st trimester, which is clearly the most critical period in the organogenesis.
The recent emergence on the drug market of synthetic cannabimimetics/SC ('spice')
may represent a new challenge for clinicians. OBJECTIVE: A literature overview on
the teratogenicity profile of both cannabis and synthetic cannabimimetics was
here carried out. METHOD: The PubMed database was searched in order to collect
all relevant cases and data regarding the possible evidence of teratogenicity
issues associated with cannabis and SC intake. RESULTS: The use of cannabis in
pregnant women has been associated with a plethora of both obstetrical/
gestational complications and neurobehavioral/neurological effects on newborns.
Conversely, only few and conflicting data are related to SC misuse issues.
CONCLUSION: Although cannabis use may be considered a risk factor for the
occurrence of pregnancyrelated morbidity issues, many studies relied on self
reports and showed inconsistent results when controlling for potential
confounders, including tobacco use. Given the role of the endocannabinoid system
in both pregnancy and delivery, SC potency at interacting with the
endocannabinoid system may be a reason of concern. Clinicians should carefully
assess each woman planning a pregnancy, or who is pregnant already, and who is at
risk of persisting in her current cannabis and/or SC intake. A nonjudgmental
approach, aiming at collecting both a history of drug/alcohol use and at
providing information regarding the risks associated with cannabis/SC intake
during pregnancy is here advised.
PMID- 28412918
TI - Neurological Aspects of Medical Use of Cannabidiol.
AB - BACKGROUND: Cannabidiol (CBD) is among the major secondary metabolites of
Cannabis devoid of the delta-9-tetra-hydrocannabinol psychoactive effects. It is
a resorcinol-based compound with a broad spectrum of potential therapeutic
properties, including neuroprotective effects in numerous pathological
conditions. CBD neuroprotection is due to its antioxidant and antiinflammatory
activities and the modulation of a large number of brain biological targets
(receptors, channels) involved in the development and maintenance of
neurodegenerative diseases. OBJECTIVE: The aim of the present review was to
describe the state of art about the pre-clinical research, the potential use and,
when existing, the clinical evidence related to CBD in the neurological field.
METHOD: Collection of all the pre-clinical and clinical findings carried out
investigating the effects of CBD alone, not in combination with other substances,
in the neurological arena with the exclusion of studies on neuropsychiatric
disorders. RESULTS: Laboratory and clinical studies on the potential role of CBD
in Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS),
Huntington's disease (HD), amyotrophic lateral sclerosis ALS), cerebral ischemia,
were examined. CONCLUSION: Pre-clinical evidence largely shows that CBD can
produce beneficial effects in AD, PD and MS patients, but its employment for
these disorders needs further confirmation from well designed clinical studies.
CBD pre-clinical demonstration of antiepileptic activity is supported by recent
clinical studies in human epileptic subjects resistant to standard antiepileptic
drugs showing its potential use in children and young adults affected by
refractory epilepsy. Evidence for use of CBD in PD is still not supported by
sufficient data whereas only a few studies including a small number of patients
are available.
PMID- 28412919
TI - Neurological Disorders in Medical Use of Cannabis: An Update.
AB - BACKGROUND & OBJECTIVE: Medical cannabis is increasingly used as a treatment or
adjunct treatment with different levels of efficacy in several neurological
disorders or related symptoms (such as multiple sclerosis, autism, Parkinson and
Alzheimer disease, Tourette's syndrome, Huntington's disease, neuropathic pain,
epilepsy, headache), as well as in other medical conditions (e.g. nausea and
vomiting, glaucoma, appetite stimulation, cancer, inflammatory conditions,
asthma). Nevertheless, a number of neurological adverse effects from use of
medical cannabis on the short- and on the longterm have been reported, in
addition to other adverse health events. CONCLUSION: It has been noticed that the
use of medical cannabis can lead to a paradoxical effects depending on the amount
of delta-9-tetrahydrocannabinol (THC) -like cannabinoids the preparation contain.
Accordingly, some neurological disorders or symptoms (e.g. multiple sclerosis,
seizures, epilepsy, headache) may be caused or exacerbated by the same treatment
supposed to cure them. The current review presents an update of the neurological
adverse effects resulting from the use of cannabis for medical purposes,
highlighting the need to weigh the benefits and risks, when using
cannabinoidbased treatments.
PMID- 28412920
TI - Neuropsychiatric and General Interactions of Natural and Synthetic Cannabinoids
with Drugs of Abuse and Medicines.
AB - BACKGROUND & OBJECTIVE: Cannabis is the most widely used illicit drug. The two
most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and
cannabidiol (CBD). The THC content of cannabis has been increasing during the
last years and recently appeared in the market as a series of synthetic
cannabinoids with potent agonist activity. Recreational users frequently combine
cannabis with other drugs of abuse as alcohol, amphetamines and derivatives,
nicotine and cocaine. In addition, these subjects can be taking medicines for
acute and chronic medical conditions. The increasing use of medicinal cannabis
for chronic pain and neurological and psychiatric disorders can produce potential
interactions with medications used for the symptomatic treatment of these or
other diseases. CONCLUSION: THC and CBD are metabolized mainly in the liver by
cytochrome P-450 isoenzymes (mainly CYP2Cs and CYP3A4). In vitro studies indicate
that THC and CBD both inhibit CYP1A1, 1A2 and 1B1 enzymes, and recent studies
have indicated that CBD is also a potent inhibitor of CYP2C19 and CYP3A4. Both
cannabinoids may interact with other medications metabolized by the same pathway
or by inducers/inhibitors of the isoenzymes. Cannabis produces sedation, impairs
psychomotor performance, and increases blood pressure and heart rate.
Pharmacodynamic interactions with other sedatives can potentiate the central
effects but can be decreased by psychostimulants. This review focuses on the
interactions between cannabinoids and alcohol, other drugs of abuse, and
prescription medicines.
PMID- 28412921
TI - Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset.
AB - BACKGROUND: Synthetic Cannabinoids (SC) are the widest and most diffused class of
Novel Psychoactive Substances. The short- and long- term health risks associated
with the consumption of SC are often unknown to both users and health
professionals. This review aims to provide a synthesis of the most recent and
relevant insights on the pharmacology, clinical and psychopathological aspects of
SC. METHOD: A structured search of two bibliographic databases (PubMed and
Scopus) was undertaken according to inclusion/exclusion criteria. The following
terms "synthetic cannabinoid*", "synthetic cannabimimetic*", "synthetic
cannabis", "synthetic marijuana" and "Spice AND cannabinoid*" were used as search
strings. RESULTS: 162 relevant results, mainly published in the past two years
were revealed. Most results emerged for the keyword "synthetic cannabinoid*",
followed by the combination "Spice* AND "cannabinoid*". Most papers were
epidemiological, forensic, toxicologic, or analytical. The results of studies
were systematized according their contribution to the comprehension of
pharmacological, clinical and psychopathological effects of SC. Fifteen SC
related fatality cases were reviewed according to their histories, pathology and
toxicology findings. CONCLUSION: The findings of this review confirm the
importance of prompt and reliable information available for health professionals
More specific analytic techniques and designed preventive strategies are required
to face unprecedented SC challenge.
PMID- 28412922
TI - Abnormalities in Kynurenine Pathway Metabolism in Treatment-Resistant Depression
and Suicidality: A Systematic Review.
AB - Treatment resistant depression (TRD) and suicidal behavior are among the most
important public health problems and are commonly associated with significant
disability and psychosocial impairment. Although there have been recent advances
in identifying the neurobiological correlates of these complex conditions, their
pathophysiology still remains unclear. Compared to non-suicidal subjects, higher
mean concentrations of inflammatory mediators have been found in both the
periphery and brain of individuals at risk for suicide. Several lines of evidence
suggest that neuroinflammation is accompanied by a dysregulation of the
kynurenine pathway (KP) in both TRD and suicidal individuals, resulting in an
imbalance of neuroactive metabolites. In particular, neuroinflammation may
trigger an increased production of the N-Methyl-D-aspartate (NMDA) receptor
agonist quinolinic acid and a concomitant reduction of neuroprotective
metabolites, potentially causing downstream effects in glutamatergic systems
resulting in depressive symptoms and suicidal behavior. This systematic review of
the current literature is mainly aimed to summarize the most important evidence
pertaining to KP metabolism abnormalities in TRD and suicidal behavior. Targeting
the KP enzymes may provide innovative approaches in the management of both TRD
and suicidality.
PMID- 28412923
TI - FDG-PET/CT Predicts Outcome in Oropharingeal Carcinoma Patients Undergoing
Intensity Modulated Radiation Therapy with Dose Escalation to FDG-avid Tumour
Volumes.
AB - OBJECTIVE: To evaluate the predictive value of FDG-PET/CT parameters on outcome
of oropharyngeal squamocellular cancer (OSCC) patients undergoing helical
tomotherapy (HTT), with dose escalation to FDG-PET/CT positive tumour volumes
using the simultaneous integrated boost (SIB) technique. MATERIALS AND METHODS:
We analysed 41 patients studied by FDG-PET/CT and treated with radical intent
between 2005 and 2014 for OSCC. HTT-SIB was delivered in 30 fractions
concomitantly: 69 Gy, as SIB, to the PET-positive volume (biological target
volume - BTV-PET), both to the primary tumour (T) and lymph nodes (N), 66 Gy to
the T and positive N, 54 Gy to the laterocervical nodes at risk. Selected PET
parameters were recovered: maximum and mean standardized uptake values (SUVmax
and SUVmean, respectively), metabolic tumour volume (MTV) and total lesion
glycolysis (TLG) obtained with different thresholds (40-50-60% of the SUVmax) for
T and N. The correlation between these parameters and the 3-year overall (OS),
cancer specific (CSS), disease free (DFS), local relapse free for T and N (LRFS-T
and LRFS-N) and distant metastasis free (DMFS) survivals was investigated.
RESULTS: The median follow-up was 37 months (range: 3-125). The 3-year OS, CSS,
DFS, LRFST, LRFS-N and DMFS were 86%, 88%, 76%, 83%, 88% and 91%, respectively.
BTVT+ N>30.9cc and BTV-T>22.4cc were correlated with CSS (p=0.02) and OS
(p=0.006) respectively; TLG-T-60>34.6cc was correlated with CSS (p=0.04) and OS
(p=0.01). MTV-T-60>4.4cc could predict a higher risk of relapse/death (CSS:
p=0.033; hazard ratio (HR) =10.92; OS: p=0.01; HR=16.4; LRFS-T: p=0.02; HR=13.90;
LRFS-T+N: p=0.03; HR=6.50). CONCLUSION: PET parameters predicted survival
outcomes and may be considered in the future in the implementation of more
personalized treatment schedules in patients affected by OSCC undergoing
radiotherapy. FDG-PET/CT dose escalated HTT-SIB allowed very promising 3-year
disease control rates in OSCC patients.
PMID- 28412924
TI - Neurons vs. Germline: A War of Hormetic Tradeoffs.
AB - The process of human ageing is significantly dependent upon events which are
currently shaping humanity. One such event is the seemingly inexorable progress
of technology, and specifically, digital communications technology. Technology
and biology are tightly interconnected, and this has a direct relevance on how
our own ageing mechanisms are evolving and adapting to the change. One way
technology may affect biological ageing is based on the concept of information
exposure which acts as a hormetic stimulus and up-regulates neuronal stress
response pathways. In this way, neurons become increasingly more likely to
acquire repair resources and function for longer, with a consequent overall
improvement in healthy lifespan. At the same time, germline repair mechanisms may
need to be downgraded in order to accommodate a tradeoff: a corresponding
escalation of repairs in neurons. In this Opinion paper, it is discussed that how
a meaningful and intentional integration with technology, which hormetically
challenges our cognition, may redress the conflict for resources between the soma
and the germline, and result in a reduction of age-related dysfunction in the
subjects.
PMID- 28412925
TI - Support and Social Contact as a Decisive Meta-Variable in Morbidity and Social
Welfare of the Older Person.
AB - : Bacground: This article tackles social support as a meta-variable that is
reinforced by a set of social variables, which correlate and act as predictors of
social welfare and life quality of the older person. OBJECTIVE: The objective of
the study is to know how social support, networks and social contacts can
influence the health of the elderly person, especially if these are interrelated
factors. METHOD: The population studied are individuals from both sexes living in
Toledo (Spanish people) and who were 65 years of age or over. Several scales were
applied to assess the frequency of and the degree of satisfaction with perceived
social support received from different sources in relation to social support. The
co relational analysis showed significant positive associations between scores
and measures of and social support, social relations, contact and social
networks. RESULTS: We conclude that the support in general is very good, over 90%
of people from the sample have someone who would help if needed. Social and
health factors are interrelated with social support. Social contact can also be
considered as a life quality estimate. He progressive loss of contact over the
years is a social factor that affects the quality of life. CONCLUSION: The meta
analysis we find that social support and the emotional factor, along with social
interactions, have powerful effects on preventing morbidity and mortality, which
are important social indicators. We conclude that social support based on
positive social interactions provides an optimal state of health in the older
person.
PMID- 28412926
TI - Acute Symptomatic Seizures in Geriatric Patients with Multiple Risk Factors - A
Diagnostic Challenge.
AB - BACKGROUND: Acute symptomatic seizures and epileptic disorders are frequent
health problems of elderly patients. An early and reliable distinction of the
seizure etiology is important to ensure adequate treatment, and to prevent
unwarranted diagnostic and therapeutic procedures. METHODS: We review the current
literature based on a MEDLINE search, describe age-related problems in detail,
with particular attention to clinical practice, discuss possible criteria and
potential pitfalls for diagnostics, and provide a compilation of etiologic
factors for acute symptomatic seizures. RESULTS: The most common causes of acute
symptomatic seizures - acute cerebrovascular disorders, metabolic disorders,
traumatic brain injury, meningo-encephalitis, cerebral tumors, and withdrawal of
alcohol and other central agents - are well-defined and seem to permit
straightforward diagnostic and therapeutic strategies. The current classification
of seizures and epileptic syndromes apparently provides clear definitions.
However, multiple age-related risk factors, as well as a reduced discriminatory
power of clinical and technical diagnostic criteria can make the distinction
difficult. CONCLUSION: Typical age-related problems are incomplete or missing
medical history, dementia, oligosymptomatic seizures, inconclusive EEG and
cerebral imaging results, multiple pathological findings and comorbidity with
ambiguous significance, confounding sleep disorders, intake of proconvulsive
drugs, and psychogenic seizures. All diagnostic and therapeutic decisions need to
be based on an integrative and individual approach that includes diagnostic
findings and risk factors, the intake of medications and other agents, and the
social situation of the elderly patient.
PMID- 28412927
TI - Widespread subcutaneous necrosis in spotted fever group Rickettsioses from the
coastal belt of Sri Lanka- a case report.
AB - BACKGROUND: Spotted fever group rickettsioses (SFGR) transmitted mostly by ticks
are increasingly discovered around the World and some of them are either re
emerging or emerging in Sri Lanka. Accidental human infections caused by these
vector borne zoonotic diseases generally give rise to nonspecific acute febrile
illnesses which can be complicated by multi organ involvement carrying high
morbidity and mortality. Nonspecific clinical features and non-availability of
early diagnostic facilities are known to result in delay in the diagnosis of
rickettsial infections. Therefore, awareness of their prevalence and more
importantly their clinical features would be help in the early diagnosis and
institution of appropriate therapy. CASE PRESENTATION: A 39-year-old otherwise
healthy female presented with an acute febrile illness complicated by severe
small joint and large joint arthritis, jaundice, acute kidney injury and
disseminated intravascular coagulation (DIC) mimicking palindromic rheumatism or
severe sepsis. She later developed a widespread fern-leaf pattern necrotic skin
rash with evidence of vasculitis on the palms and soles, aiding the clinical
diagnosis of SFGR. She had very high antibody titres against R. conorii antigen
confirming the diagnosis and recovered completely with anti-rickettsial therapy.
CONCLUSION: We feel that clinicians should be aware of the unusual clinical
presentations such as purpura fulminans and 'fern-leaf' pattern necrotic skin
rash of SFGR infection. Such knowledge would not only benefit those who practice
in tropics with limited diagnostic facilities but also would improve the
management of acute febrile illness in returning travelers who visit endemic
areas.
PMID- 28412928
TI - Poplar stem transcriptome is massively remodelled in response to single or
repeated mechanical stimuli.
AB - BACKGROUND: Trees experience mechanical stimuli -like wind- that trigger
thigmomorphogenetic syndrome, leading to modifications of plant growth and wood
quality. This syndrome affects tree productivity but is also believed to improve
tree acclimation to chronic wind. Wind is particularly challenging for trees,
because of their stature and perenniality. Climate change forecasts are
predicting that the occurrence of high wind will worsen, making it increasingly
vital to understand the mechanisms regulating thigmomorphogenesis, especially in
perennial plants. By extension, this also implies factoring in the recurring
nature of wind episodes. However, data on the molecular processes underpinning
mechanoperception and transduction of mechanical signals, and their dynamics, are
still dramatically lacking in trees. RESULTS: Here we performed a genome-wide and
time-series analysis of poplar transcriptional responsiveness to transitory and
recurring controlled stem bending, mimicking wind. The study revealed that 6% of
the poplar genome is differentially expressed after a single transient bending.
The combination of clustering, Gene Ontology categorization and time-series
expression approaches revealed the diversity of gene expression patterns and
biological processes affected by stem bending. Short-term transcriptomic
responses entailed a rapid stimulation of plant defence and abiotic stress
signalling pathways, including ethylene and jasmonic acid signalling but also
photosynthesis process regulation. Late transcriptomic responses affected genes
involved in cell wall organization and/or wood development. An analysis of the
molecular impact of recurring bending found that the vast majority (96%) of the
genes differentially expressed after a first bending presented reduced or even
net-zero amplitude regulation after the second exposure to bending. CONCLUSION:
This study constitutes the first dynamic characterization of the molecular
processes affected by single or repeated stem bending in poplar. Moreover, the
global attenuation of the transcriptional responses, observed from as early as
after a second bending, indicates the existence of a mechanism governing a fine
tuning of plant responsiveness. This points toward several mechanistic pathways
that can now be targeted to elucidate the complex dynamics of wind acclimation.
PMID- 28412929
TI - Testosterone, territorial response, and song in seasonally breeding tropical and
temperate stonechats.
AB - BACKGROUND: Testosterone facilitates physiological, morphological, and behavioral
changes required for breeding in male vertebrates. However, testosterone
concentrations and the link between its seasonal changes and those in
reproductive behaviors vary greatly among species. To better understand the
impact of tropical and temperate environments and life history factors on this
variation, we have compared testosterone, territorial behavior and song
performance across sequential stages of the breeding season in males of 16
closely related taxa of East African tropical and West European temperate
stonechats (Saxicola spp), which all breed during a short breeding season, but
differ in migratory behavior, seasonal territory-acquisition and pace of life.
RESULTS: We found that generally, the profiles of testosterone and territorial
behavior were similar across latitudes. African stonechats with a slow pace of
life had equally high peak testosterone concentrations and responded as
aggressively to an intruder as European stonechats with a fast pace of life.
However, song performance at the beginning of the breeding season was lower in
African than in European stonechats. The differences in song performance were not
associated with variation in testosterone levels between tropical and temperate
stonechats. CONCLUSIONS: The results suggest a very similar role for testosterone
as a mediator of high intensity territorial aggression during the fertile period
of females in tropical and temperate stonechats, which all are highly seasonal,
locally synchronous breeders. A potential explanation may be high risk of extra
pair copulations which has been associated with synchronous breeding.
Interestingly, an association was not consistent for song performance. Our data
suggest that song performance can be disassociated from peak testosterone levels
depending on its role in breeding behavior. Despite similar testosterone levels,
European males, which early in the breeding season acquire territories and mates,
showed greater song performance than African stonechats, which maintain year
round territories and pair-bonds. Taken together, our study comparing related
taxa of old world songbirds suggests that short breeding seasons may be a major
selective force for high peak testosterone levels during breeding regardless of
latitude and pace of life, but that particular behaviors, in our case song, can
be uncoupled from peak testosterone levels.
PMID- 28412930
TI - Large-scale analysis of post-translational modifications in E. coli under glucose
limiting conditions.
AB - BACKGROUND: Post-translational modification (PTM) of proteins is central to many
cellular processes across all domains of life, but despite decades of study and a
wealth of genomic and proteomic data the biological function of many PTMs remains
unknown. This is especially true for prokaryotic PTM systems, many of which have
only recently been recognized and studied in depth. It is increasingly apparent
that a deep sampling of abundance across a wide range of environmental stresses,
growth conditions, and PTM types, rather than simply cataloging targets for a
handful of modifications, is critical to understanding the complex pathways that
govern PTM deposition and downstream effects. RESULTS: We utilized a deeply
sampled dataset of MS/MS proteomic analysis covering 9 timepoints spanning the
Escherichia coli growth cycle and an unbiased PTM search strategy to construct a
temporal map of abundance for all PTMs within a 400 Da window of mass shifts.
Using this map, we are able to identify novel targets and temporal patterns for N
terminal N alpha acetylation, C-terminal glutamylation, and asparagine
deamidation. Furthermore, we identify a possible relationship between N-terminal
N alpha acetylation and regulation of protein degradation in stationary phase,
pointing to a previously unrecognized biological function for this poorly
understood PTM. CONCLUSIONS: Unbiased detection of PTM in MS/MS proteomics data
facilitates the discovery of novel modification types and previously unobserved
dynamic changes in modification across growth timepoints.
PMID- 28412931
TI - Prevalence of Escherichia coli O157:H7 in beef cattle at slaughter and beef
carcasses at retail shops in Ethiopia.
AB - BACKGROUND: There is paucity of information regarding the epidemiology of
Escherichia coli O157: H7 in developing countries. In this study, we investigated
the occurrence of E. coli O157: H7 associated with beef cattle at processing
plants and at retail shops in Ethiopia. METHODS: Various samples were collected
from beef cattle at slaughter/processing plants, carcass at retail shops and
humans at health centers. E. coli O157: H7 was isolated, identified and
characterized for antimicrobial resistance, using standard microbiological
methods. RESULTS: At the processing plants E. coli O157: H7 was detected in 1.89%
of fecal, 0.81% of intestinal mucosal swab, 0.54% of skin swab and 0.54% of
carcass internal swab samples. At retail shops it was detected in 0.8% of carcass
and 0.8% of cutting board swab samples, while all samples from utensils, hands
from workers, and fecal and stool samples were negative. All isolates were
resistant to Amoxicillin, moderately resistant to Cefoxitine and Nitrofurantoins
but susceptible to other antimicrobials tested. CONCLUSIONS: E. coli O157: H7
occurs at low prevalence in beef cattle, and the current sanitary dressing
procedures in the processing plants and storage conditions in the retail shops
are effective against E. coli O157: H7.
PMID- 28412932
TI - Isolation of enterococci, their antimicrobial susceptibility patterns and
associated factors among patients attending at the University of Gondar Teaching
Hospital.
AB - BACKGROUND: Enterococci become clinically important especially in immune
compromised patients and important causes of nosocomial infections. Data on the
prevalence, antimicrobial susceptibility patterns and associated factors of
enterococci are scarce in Ethiopia. METHODS: A hospital based cross-sectional
study was conducted at the University of Gondar Teaching Hospital from February
28, 2014 to May 1, 2014. Pretested structured questionnaire was used to collect
socio-demographic data and possible associated factors of enterococci infections.
Clinical samples including urine, blood, wound swabs and other body fluids from
patients requested by physician for culture and antimicrobial susceptibility test
during the study period were included. A total of 385 patients were included in
the study. Data were entered and analyzed using SPSS Version 20. P values <0.05
were considered as statistically significant. RESULT: The overall prevalence of
enterococci infection was 6.2% (24/385). The commonest sites of infections were
urinary tract followed by wound and blood. Among the 24 isolates, 33.3% (8/24)
were resistant to all tested antimicrobial agents. Forty one point 7 % (10/24) of
the enterococci isolates were vancomycin resistant enterococci (VRE). Moreover,
two third of the isolates were multidrug resistant (MDR) enterococci. In
multivariate analysis, duration of hospital stay for two days and more than two
days with infection rate 17/32 (53.1%), previous history of any antibiotics (AOR
= 9.13; [95% CI; 2.01-41.51] P = 0.00) and history of urinary catheterization
(AOR = 8.80; [95% CI; 1.70-45.64] P = 0.01) were associated with presence of
higher enterococci infections than their respective groups. CONCLUSION: The
prevalence of enterococci infections among patients with UTIs, wound infections
and sepsis were higher than the other infections. Multi drug resistant
enterococci including VRE were isolated from clinical samples in the study area.
Being hospitalized for >=48 h, having history of any antibiotic administration
and catheterization were associated factors for enterococci infections. Presence
of VRE indicates decreased antibiotic treatment options of multidrug resistant
enterococci. Therefore, efforts should be made to prevent enterococci infections
and emergency of multidrug resistant enterococci. Moreover, species
identification and antibiotic resistant in advanced and at large scale is
demanding.
PMID- 28412933
TI - Beyond quality of life: a cross sectional study on the mental health of patients
with chronic kidney disease undergoing dialysis and their caregivers.
AB - BACKGROUND: Patients with terminal chronic kidney disease (CKDT) requiring renal
replacement therapies (RRT) undergo important changes in living habits and
frequently need caregiving. These patients and their caregivers are risk groups
for the development of physical and psychological symptoms. This study aimed to
evaluate the prevalence of anxiety, depression, stress, fatigue, social support,
and quality of life in patients with CKD and their caregivers. METHOD: This cross
sectional study was conducted with 21 patients and their caregivers, from January
to September 2015. We included patients aged over 18 years, with at least 6
months on dialysis treatment, and caregivers who were family members. The
participants' social, demographic, clinical, laboratory, and psychological
variables were evaluated. A descriptive analysis and an examination of the
association between patients and caregivers were performed. RESULTS: Among
patients, we observed that 38.1% had symptoms that indicated anxiety and
depression. The average score for practical social support was 3.15 +/- 0.769 and
that for emotional social support was 3.16 +/- 0.79. As for fatigue, 14.3% of
patients reported being 'extremely tired' and 14.3% reported that they engaged in
all the activities they usually performed before the illness. Further, 57.1%
presented stress, and of these, 66.7% were at the resistance stage, with
predominance of psychological symptoms in 60.0%. The quality of life domain in
terms of functional capacity (FC) presented a correlation with haemoglobin level
(r = 0.581, p = 0.006) and non-anaemic patients presented better FC. Among
caregivers, we observed symptoms that indicated anxiety and depression in 33.3%
of the sample. Caregivers exhibited an average score of 2.88 +/- 0.77 for
practical social support and 3.0 +/- 0.72 for emotional social support. Further,
14.3% reported being 'extremely tired' and 28.8% reported that they engaged in
all activities that they usually performed before the patient's illness. When
comparing the two groups (patients vs. caregivers), we observed that they
presented similar results for the presence of anxiety, depression, and fatigue.
Caregivers received less social support than patients did. Both groups presented
similar predominance of stress levels; however, patients presented more
predominance of psychological symptoms. With reference to quality of life,
patients and caregivers presented similar results on the social aspects,
vitality, mental health, and mental domains. CONCLUSION: The mental health
characteristics of patients and caregivers were similar, and within the context
of dialysis for renal disease, both must undergo specific interventions.
PMID- 28412934
TI - Karyotype diversity and chromosomal organization of repetitive DNA in Tityus
obscurus (Scorpiones, Buthidae).
AB - BACKGROUND: Holocentric chromosomes occur in approximately 750 species of
eukaryotes. Among them, the genus Tityus (Scorpiones, Buthidae) has a labile
karyotype that shows complex multivalent associations during male meiosis. Thus,
taking advantage of the excellent model provided by the Buthidae scorpions, here
we analyzed the chromosomal distribution of several repetitive DNA classes on the
holocentric chromosomes of different populations of the species Tityus obscurus
Gervais, 1843, highlighting their involvement in the karyotypic differences found
among them. RESULTS: This species shows inter- and intrapopulational karyotype
variation, with seven distinct cytotypes: A (2n = 16), B (2n = 14), C (2n = 13),
D (2n = 13), E (2n = 12), F (2n = 12) and G (2n = 11). Furthermore, exhibits
achiasmatic male meiosis and lacks heteromorphic sex chromosomes. Trivalent and
quadrivalent meiotic associations were found in some cytotypes. In them, 45S
rDNAs were found in the terminal portions of two pairs, while TTAGG repeats were
found only at the end of the chromosomes. In the cytotype A (2n = 16), the U2
snRNA gene mapped to pair 1, while the H3 histone cluster and C 0 t-1 DNA
fraction was terminally distributed on all pairs. Mariner transposons were found
throughout the chromosomes, with the exception of one individual of cytotype A
(2n = 16), in which it was concentrated in heterochromatic regions. CONCLUSIONS:
Chromosomal variability found in T. obscurus are due to rearrangements of the
type fusion/fission and reciprocal translocations in heterozygous. These
karyotype differences follow a geographical pattern and may be contributing to
reproductive isolation between populations analyzed. Our results also demonstrate
high mobility of histone H3 genes. In contrast, other multigene families (45S
rDNA and U2 snRNA) have conserved distribution among individuals. The
accumulation of repetitive sequences in distal regions of T. obscurus
chromosomes, suggests that end of chromosome are not covered by the kinetochore.
PMID- 28412935
TI - Fitness costs of symbiont switching using entomopathogenic nematodes as a model.
AB - BACKGROUND: Steinernematid nematodes form obligate symbioses with bacteria from
the genus Xenorhabdus. Together Steinernema nematodes and their bacterial
symbionts successfully infect, kill, utilize, and exit their insect hosts. During
this process the nematodes and bacteria disassociate requiring them to re
associate before emerging from the host. This interaction can be complicated when
two different nematodes co-infect an insect host. RESULTS: Non-cognate nematode
bacteria pairings result in reductions for multiple measures of success,
including total progeny production and virulence. Additionally, nematode
infective juveniles carry fewer bacterial cells when colonized by a non-cognate
symbiont. Finally, we show that Steinernema nematodes can distinguish
heterospecific and some conspecific non-cognate symbionts in behavioral choice
assays. CONCLUSIONS: Steinernema-Xenorhabdus symbioses are tightly governed by
partner recognition and fidelity. Association with non-cognates resulted in
decreased fitness, virulence, and bacterial carriage of the nematode-bacterial
pairings. Entomopathogenic nematodes and their bacterial symbionts are a useful,
tractable, and reliable model for testing hypotheses regarding the evolution,
maintenance, persistence, and fate of mutualisms.
PMID- 28412936
TI - 1H-NMR analysis of feces: new possibilities in the helminthes infections
research.
AB - BACKGROUND: Analysis of the stool samples is an essential part of routine
diagnostics of the helminthes infections. However, the standard methods such Kato
and Kato-Katz utilize only a fraction of the information available. Here we
present a method based on the nuclear magnetic resonance spectroscopy (NMR) which
could be auxiliary to the standard procedures by evaluating the complex metabolic
profiles (or phenotypes) of the samples. METHOD: The samples were collected over
the period of June-July 2015, frozen at -20 degrees C at the site of collection
and transferred within four hours for the permanent storage at -80 degrees C.
Fecal metabolites were extracted by mixing aliquots of about 100 mg thawed stool
material with 0.5 mL phosphate buffer saline, followed by the homogenization and
centrifugations steps. All NMR data were recorded using a Bruker 600 MHz AVANCE
II spectrometer equipped with a 5 mm triple resonance inverse cryoprobe and a z
gradient system. RESULTS: Here we report an optimized method for NMR based
metabolic profiling/phenotyping of the stools samples. Overall, 62 metabolites
were annotated in the pool sample using the 2D NMR spectra and the Bruker
Biorefcode database. The compounds cover a wide range of the metabolome including
amino acids and their derivatives, short chain fatty acids (SCFAs), carboxylic
acids and their derivatives, amines, carbohydrates, purines, alcohols and others.
An exploratory analysis of the metabolic profiles reveals no strong trends
associated with the infection status of the patients. However, using the
penalized regression as a variable selection method we succeeded in finding a
subset of eleven variables which enables to discriminate the patients on basis of
their infections status. CONCLUSIONS: A simple method for metabolic
profiling/phenotyping of the stools samples is reported and tested on a pilot
opisthorchiasis cohort. To our knowledge this is the first report of a NMR-based
feces analysis in the context of the helminthic infections.
PMID- 28412937
TI - Understanding relevance of health research: considerations in the context of
research impact assessment.
AB - BACKGROUND: With massive investment in health-related research, above and beyond
investments in the management and delivery of healthcare and public health
services, there has been increasing focus on the impact of health research to
explore and explain the consequences of these investments and inform strategic
planning. Relevance is reflected by increased attention to the usability and
impact of health research, with research funders increasingly engaging in
relevance assessment as an input to decision processes. Yet, it is unclear
whether relevance is a synonym for or predictor of impact, a necessary condition
or stage in achieving it, or a distinct aim of the research enterprise. The main
aim of this paper is to improve our understanding of research relevance, with
specific objectives to (1) unpack research relevance from both theoretical and
practical perspectives, and (2) outline key considerations for its assessment.
APPROACH: Our approach involved the scholarly strategy of review and reflection.
We prepared a draft paper based on an exploratory review of literature from
various fields, and gained from detailed and insightful analysis and critique at
a roundtable discussion with a group of key health research stakeholders. We also
solicited review and feedback from a small sample of expert reviewers.
CONCLUSIONS: Research relevance seems increasingly important in justifying
research investments and guiding strategic research planning. However,
consideration of relevance has been largely tacit in the health research
community, often depending on unexplained interpretations of value, fit and
potential for impact. While research relevance seems a necessary condition for
impact - a process or component of efforts to make rigorous research usable -
ultimately, relevance stands apart from research impact. Careful and explicit
consideration of research relevance is vital to gauge the overall value and
impact of a wide range of individual and collective research efforts and
investments. To improve understanding, this paper outlines four key
considerations, including how research relevance assessments (1) orientate to,
capture and compare research versus non-research sources, (2) consider both
instrumental versus non-instrumental uses of research, (3) accommodate dynamic
temporal-shifting perspectives on research, and (4) align with an intersubjective
understanding of relevance.
PMID- 28412939
TI - Diagnostic validity of the STRATIFY and Downton instruments for evaluating the
risk of falls by hospitalised acute-care patients: a multicentre longitudinal
study.
AB - BACKGROUND: Falls are major adverse events in hospitals. The appropriateness of
using risk assessment instruments for falls in hospitals has recently been
questioned, although the research performed in this respect presents some
methodological shortcomings. The purpose of the present study is to evaluate the
accuracy of the Downton and STRATIFY instruments to determine the risk of falls
and to predict their incidence in acute care hospitals in the public health
system in Andalusia (Spain). METHODS: A longitudinal, multicentre prospective
study was made of a cohort of patients recruited between May 2014 and March 2016.
The risk of falls was assessed using each of the above instruments during the
first 24 h after hospital admittance, with later re-evaluations every 72 h until
discharge. Descriptive statistics were obtained, bivariate and multivariate
analysis were performed. The diagnostic validity of the process was assessed by
calculations of sensitivity, specificity, positive and negative predictive values
and ratios of positive and negative likelihood. ROC curve analysis was performed
for both instruments. RESULTS: For this study, 1247 patients were recruited, of
whom 977 completed all the follow-up assessments. Twenty-three of these patients
(2.35%) suffered 24 falls. ROC curve analysis showed that the optimal cut-off
point for each assessment instrument was below that described by the authors: AUC
STRATIFY = 0.69 (95% CI: 0.57-0.8); AUC Downton = 0.6 (95% CI: 0.48-0.72). With a
cut-off point of 1, the sensitivity of STRATIFY was 47.6% and its specificity,
85%. With a cut-off point of 2, Downton presented a sensitivity of 66.7% and a
specificity of 55.3%. CONCLUSIONS: The Downton and STRATIFY falls risk assessment
instruments presented little utility as means of detecting the risk of falls
among a sample of adult patients admitted to acute care hospitals. Fall
prevention in hospitals should be based on the study of individual risk factors.
PMID- 28412938
TI - Broad and flexible stable isotope niches in invasive non-native Rattus spp. in
anthropogenic and natural habitats of central eastern Madagascar.
AB - BACKGROUND: Rodents of the genus Rattus are among the most pervasive and
successful invasive species, causing major vicissitudes in native ecological
communities. A broad and flexible generalist diet has been suggested as key to
the invasion success of Rattus spp. Here, we use an indirect approach to better
understand foraging niche width, plasticity, and overlap within and between
introduced Rattus spp. in anthropogenic habitats and natural humid forests of
Madagascar. RESULTS: Based on stable carbon and nitrogen isotope values measured
in hair samples of 589 individual rodents, we found that Rattus rattus had an
extremely wide foraging niche, encompassing the isotopic space covered by a
complete endemic forest-dwelling Malagasy small mammal community. Comparisons of
Bayesian standard ellipses, as well as (multivariate) mixed-modeling analyses,
revealed that the stable isotope niche of R. rattus tended to change seasonally
and differed between natural forests and anthropogenic habitats, indicating
plasticity in feeding niches. In co-occurrence, R. rattus and Rattus norvegicus
partitioned feeding niches. Isotopic mismatch of signatures of individual R.
rattus and the habitat in which they were captured, indicate frequent dispersal
movements for this species between natural forest and anthropogenic habitats.
CONCLUSIONS: Since R. rattus are known to transmit a number of zoonoses,
potentially affecting communities of endemic small mammals, as well as humans,
these movements presumably increase transmission potential. Our results suggest
that due to their generalist diet and potential movement between natural forest
and anthropogenic habitats, Rattus spp. might affect native forest-dependent
Malagasy rodents as competitors, predators, and disease vectors. The combination
of these effects helps explain the invasion success of Rattus spp. and the
detrimental effects of this genus on the endemic Malagasy rodent fauna.
PMID- 28412940
TI - Absence of the dermatan sulfate chain of decorin does not affect mouse
development.
AB - BACKGROUND: In vitro studies suggest that the multiple functions of decorin are
related to both its core protein and its dermatan sulfate chain. To determine the
contribution of the dermatan sulfate chain to the functional properties of
decorin in vivo, a mutant mouse whose decorin lacked a dermatan sulfate chain was
generated. RESULTS: Homozygous mice expressing only the decorin core protein
developed and grew in a similar manner to wild type mice. In both embryonic and
postnatal mice, all connective tissues studied, including cartilage, skin and
cornea, appeared to be normal upon histological examination, and their collagen
fibrils were of normal diameter and organization. In addition, abdominal skin
wounds healed in an identical manner in the mutant and wild type mice.
CONCLUSIONS: The absence of a dermatan sulfate chain on decorin does not appear
to overtly influence its functional properties in vivo.
PMID- 28412941
TI - Survival prediction in Amyotrophic lateral sclerosis based on MRI measures and
clinical characteristics.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) a highly heterogeneous
neurodegenerative condition. Accurate diagnostic, monitoring and prognostic
biomarkers are urgently needed both for individualised patient care and clinical
trials. A multimodal magnetic resonance imaging study is presented, where MRI
measures of ALS-associated brain regions are utilised to predict 18-month
survival. METHODS: A total of 60 ALS patients and 69 healthy controls were
included in this study. 20% of the patient sample was utilised as an independent
validation sample. Surface-based morphometry and diffusion tensor white matter
parameters were used to identify anatomical patterns of neurodegeneration in 80%
of the patient sample compared to healthy controls. Binary logistic ridge
regressions were carried out to predict 18-month survival based on clinical
measures alone, MRI features, and a combination of clinical and MRI data.
Clinical indices included age at symptoms onset, site of disease onset,
diagnostic delay from first symptom to diagnosis, and physical disability (ALSFRS
r). MRI features included the average cortical thickness of the precentral and
paracentral gyri, the average fractional anisotropy, radial-, medial-, and axial
diffusivity of the superior and inferior corona radiata, internal capsule,
cerebral peduncles and the genu, body and splenium of the corpus callosum.
RESULTS: Clinical data alone had a survival prediction accuracy of 66.67%, with
62.50% sensitivity and 70.84% specificity. MRI data alone resulted in a
prediction accuracy of 77.08%, with 79.16% sensitivity and 75% specificity. The
combination of clinical and MRI measures led to a survival prediction accuracy of
79.17%, with 75% sensitivity and 83.34% specificity. CONCLUSION: Quantitative MRI
measures of ALS-specific brain regions enhance survival prediction in ALS and
should be incorporated in future clinical trial designs.
PMID- 28412942
TI - Breast cancer screening practices of African migrant women in Australia: a
descriptive cross-sectional study.
AB - BACKGROUND: Breast cancer is the most diagnosed cancer among women and a leading
cause of mortality and morbidity, globally. Breast cancer mortality can be
improved through routine cancer screening, yet migrant populations have lower
participation rates. While African migrants are among the fastest growing migrant
population in Australia, their breast cancer screening behaviour is under
studied. The aims of this study were to report breast cancer screening status of
African migrant women and factors associated with their breast cancer screening
behaviour in Australia. METHODS: A descriptive, cross-sectional approach was
utilised for this study. Two hundred and sixty four African migrant women aged 18
69 years and recruited from a number of organisations responded to a self
reported African version of the Breast Cancer Screening Beliefs Questionnaire
(BCSBQ). Main research variables are breast cancer screening practices and
demographic characteristics and total scores on each of the BCSBQ subscales.
Multivariable logistic regression analyses were performed to investigate the
impact of the demographic variables on the likelihood of women in the target age
range 50-74 years having screening practices as recommended. RESULTS: While most
of the participants heard of breast awareness (76.1%) and mammogram (85.2%), only
11.4% practised monthly breast awareness, whereas 65.9% had ever had a mammogram
as frequently as recommended. Age and employment were determining factors for
participating in mammogram. Significant different scores were found in the
"Practical barriers" between women at the target age who had and had not
performed breast awareness (80.4 versus 77.5, p-value = 0.002) and mammogram
(77.1 versus 70.3, p-value = 0.009) regularly as recommended. Moreover, attitudes
towards general health check-ups subscale scores were significantly higher in
women who had performed clinical breast examination as frequently as recommended
than those who had not. CONCLUSIONS: The research reveals that practical barriers
and attitudes towards general health check-ups are important factors to take into
account in determining African migrant women's participation in breast cancer
screening. Progress in reducing breast cancer deaths through early detection
needs to focus on attitudinal change among African migrants.
PMID- 28412943
TI - Generic care pathway for elderly patients in need of home care services after
discharge from hospital: a cluster randomised controlled trial.
AB - BACKGROUND: Improved discharge arrangements and targeted post-discharge follow-up
can reduce the risk of adverse events after hospital discharge for elderly
patients. Although more care is to shift from specialist to primary care, there
are few studies on post-discharge interventions run by primary care. A generic
care pathway, Patient Trajectory for Home-dwelling elders (PaTH) including
discharge arrangements and follow-up by primary care, was developed and
introduced in Central Norway Region in 2009, applying checklists at defined
stages in the patient trajectory. In a previous paper, we found that PaTH had
potential of improving follow-up in primary care. The aim of this study was to
establish the effect of PaTH-compared to usual care-for elderly in need of home
care services after discharge from hospital. METHODS: We did an unblinded,
cluster randomised controlled trial with 12 home care clusters. Outcomes were
measured at the patient level during a 12-month follow-up period for the
individual patient and analysed applying linear and logistic mixed models.
Primary outcomes were readmissions within 30 days and functional level assessed
by Nottingham extended ADL scale. Secondary outcomes were number and length of
inpatient hospital care and nursing home care, days at home, consultations with
the general practitioners (GPs), mortality and health related quality of life (SF
36). RESULTS: One-hundred and sixty-three patients were included in the PaTH
group (six clusters), and 141 patients received care as usual (six clusters). We
found no statistically significant differences between the groups for primary and
secondary outcomes except for more consultations with the GPs in PaTH group (p =
0.04). Adherence to the intervention was insufficient as only 36% of the patients
in the intervention group were assessed by at least three of the four main
checklists in PaTH, but this improved over time. CONCLUSIONS: Lack of adherence
to PaTH rendered the study inconclusive regarding the elderly's functional level,
number of readmissions after hospital discharge, and health care utilisation
except for more consultations with the GPs. A targeted exploration of
prerequisites for implementation is recommended in the pre-trial phase of complex
intervention studies. TRIAL REGISTRATION: Clinical Trials.gov NCT01107119 ,
retrospectively registered 2010.04.18.
PMID- 28412944
TI - Length of paediatric inpatient stay, socio-economic status and hospital
configuration: a retrospective cohort study.
AB - BACKGROUND: Variation in paediatric inpatient length of stay exists - whether
this is driven by differences in patient characteristics or health service
delivery is unclear. We will test the hypotheses that higher levels of
deprivation are associated with prolonged length of stay and that differences in
prolonged length of stay across 2 hospitals will be explained by demographic,
clinical and process factors. METHODS: This is a retrospective cohort study of
2889 children aged less than 16 years admitted from 1st April 2009 to 30th March
2010. Administrative data were used from two UK hospitals whose Accident and
Emergency (A&E) departments were paediatric and adult physician led respectively.
The main outcome was prolonged length of stay defined as greater than or equal to
the mean (1.8 days). Sensitivity analyses defined prolonged length of stay as
greater than the median (1 day). Demographic, clinical and process
characteristics were examined. Socio-economic position was measured by Income
Deprivation Affecting Children Index. Multivariable logistic and linear
regression analyses were performed. RESULTS: We did not find a consistent
association between length of stay and socio-economic position, using a variety
of definitions of length of stay. In contrast, adjusted for age, gender, socio
economic position, ethnicity, final diagnosis, number of hospital admissions,
source of admission, and timing of admission, admission to the adult led A&E
hospital was more strongly associated with prolonged length of stay (Odds Ratio
1.41, 95% Confidence Interval 1.16, 1.71). CONCLUSION: Local variation in
paediatric inpatient length of stay was not explained by demographic, clinical or
process factors, but could have been due to residual confounding by medical
complexity. Length of stay was not consistently associated with socio-economic
position suggesting that length of stay is a function of health service not the
determinants of health. Analyses of these types of data would be strengthened by
measures of complexity and adverse events.
PMID- 28412945
TI - Multimorbidity associated with functional independence among community-dwelling
older people: a cross-sectional study in Southern China.
AB - BACKGROUND: Multimorbidity, the coexistence of two or more chronic diseases, is
common in older adults. And it may lead to many adverse health outcomes, such as
disability. However, data on multimorbidity and its relationship with functional
independence are scarce in Asian countries. Therefore, this study aims to
investigate the relationship between multimorbidity and functional status among
older people in China. METHODS: Based on a cross-sectional survey, the
information regarding 2705 older adults, who were of at least 60 years of age,
was collected through interviews and analyzed. To assess functional status, we
used the Functional Independence Measure (FIM). Exploratory factor analysis was
performed to assess correlations among chronic diseases. Several logistic
regression models were run in the study. RESULTS: The presence of two or more
chronic conditions and the number of multimorbidity group overlaps were
independent risk factors for the loss of functional independence in older adults.
Hypertension and chronic pain, emerged as the most prevalent multimorbidity pair,
was significantly associated with functional independence (OR = 1.64, 95% CI =
1.25-2.16), followed by the co-occurrence of hypertension and heart diseases with
a lower prevalence but a higher OR compared with the former pair (OR = 1.72, 95%
CI = 1.15-2.58). Of the five multimorbidity groups used for factor analysis, the
bones and pain group (OR = 1.47, 95% CI = 1.23-1.77) and the cardiometabolic
group (OR = 1.34, 95% CI = 1.13-1.59) were both found to be significantly
correlated with lower functional independence. CONCLUSIONS: Multimorbidity was
common among older people in Southern China. Studying the relationship between
multimorbidity and functional status could be useful to find potential
correlations among chronic diseases. Additionally, it may also be meaningful to
identify multimorbidity combinations, posing an increased risk of loss of
functional independence, and further improve functional status in older adults
with comorbidities.
PMID- 28412946
TI - Big data and data repurposing - using existing data to answer new questions in
vascular dementia research.
AB - INTRODUCTION: Traditional approaches to clinical research have, as yet, failed to
provide effective treatments for vascular dementia (VaD). Novel approaches to
collation and synthesis of data may allow for time and cost efficient hypothesis
generating and testing. These approaches may have particular utility in helping
us understand and treat a complex condition such as VaD. METHODS: We present an
overview of new uses for existing data to progress VaD research. The overview is
the result of consultation with various stakeholders, focused literature review
and learning from the group's experience of successful approaches to data
repurposing. In particular, we benefitted from the expert discussion and input of
delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16
18th October 2015). RESULTS: We agreed on key areas that could be of relevance to
VaD research: systematic review of existing studies; individual patient level
analyses of existing trials and cohorts and linking electronic health record data
to other datasets. We illustrated each theme with a case-study of an existing
project that has utilised this approach. CONCLUSIONS: There are many
opportunities for the VaD research community to make better use of existing data.
The volume of potentially available data is increasing and the opportunities for
using these resources to progress the VaD research agenda are exciting. Of
course, these approaches come with inherent limitations and biases, as bigger
datasets are not necessarily better datasets and maintaining rigour and critical
analysis will be key to optimising data use.
PMID- 28412947
TI - Report of the first clinical case of intestinal trichomoniasis caused by
Tritrichomonas foetus in a cat with chronic diarrhoea in Brazil.
AB - BACKGROUND: Tritrichomonas foetus is an emergent and important enteric pathogen
of cats, which causes prolonged diarrhoea in cats. CASE PRESENTATION: This study
describes a T. foetus infection in a seven-month-old, entire male domestic
shorthair kitten with a six-month history of persistent large intestinal
diarrhoea, faecal incontinence, prostration, apathy and weight loss. Parasites
were microscopically observed and confirmed by PCR and DNA sequencing. Molecular
analyses were carried out comparing the sequence obtained in this study with T.
foetus and T. suis. Retrieved from GenBank. After treatment with ronidazole, the
cat showed resolution of clinical signs. CONCLUSIONS: This is the first clinical
case of T. foetus infection in a chronic diarrheic cat in Brazil and South
America, confirming the presence of this pathogen in this part of the world and
highlighting the importance of this protozoa being considered in the differential
diagnosis of cats presenting diarrhoea of the large intestine. Our case report
enriches our knowledge on the geographical distribution of T. foetus in cats in
Brazil and provides further understanding of the clinical significance of feline
intestinal trichomoniasis in this country.
PMID- 28412948
TI - A computerized tablet system for evaluating treatment of essential tremor by
magnetic resonance guided focused ultrasound.
AB - BACKGROUND: Transcranial magnetic resonance guided focused ultrasound is an
emerging technology under evaluation for treatment of essential tremor, a
prevalent movement disorder. A qualitative evaluation is performed by a clinician
periodically during the procedure to maximize treatment effects and minimize
adverse effects. The present work demonstrates a magnetic resonance-compatible
method to enable more precise, quantitative measurement of tremor severity.
METHODS: Tremor severity was measured in 12 patients pre-, post-, and intra
operatively, using a magnetic resonance-compatible tablet and a computerized
adaptation of drawing tasks from the widely-used Fahn-Tolosa-Marin Tremor Rating
Scale. Tremor metrics based on spectral analysis were calculated for each drawing
and compared using Wilcoxon signed rank tests. RESULTS: Tremor metrics in the
dominant (treated) hand were significantly and consistently lower post
operatively compared to pre-operatively, but there was no significant difference
in the non-dominant (untreated) hand, as expected. Intra-operative metrics were
intermediate between pre- and post-operative metrics. CONCLUSIONS: Use of the
tablet for quantitative tremor measurement was demonstrated pre-, post-, and
intra-operatively during treatment of essential tremor, complementing standard
qualitative assessment. With additional work, the system has potential to add
objectivity to clinical trials and to aid treatment decision-making by providing
a metric for optimization during the procedure, which may eventually lead to more
optimal treatment. Enhancements and further studies are suggested, and extensions
to fMRI studies of essential tremor and Parkinson's disease are also likely.
PMID- 28412949
TI - Skin whitening among Cameroonian female university students: knowledge,
attitudes, practices and motivations.
AB - BACKGROUND: Lack of data on skin whitening (SW) among Cameroonian female
university students prompted us to undertake the present study which aimed at
assessing the knowledge, attitudes, practices and motivations of female
university students vis-a-vis SW. METHODS: This was a cross-sectional study
conducted from January to April 2013 in 4 university campuses of Yaounde,
Cameroon. Any female student regularly registered in one of the study sites, who
was present at the campus when the investigator visited and volunteered to
participate in the study was enrolled. RESULTS: Overall, we recruited 620 female
students, their ages ranging from 16 to 46 years with a mean of 21.3 +/- 2.9
years. Only 87 participants (14%) found that SW was a good practice. One hundred
and sixty nine respondents (27.3%) were currently practicing SW with no age
difference when compared to their counterparts (p = 0.09). The desire to have a
uniform body skin color was the prevailing reason motivating the practice of SW
(39.1%), followed by the need to have a soft skin (29%). Assessment of levels of
knowledge regarding advantages of the black skin and deleterious effects of SW
showed excellent scores (>=75% of good answers) only in 6.1 and 0.5% of cases
respectively, with no difference between those practicing SW or not (all p values
> 0.05). CONCLUSION: The practice of SW is common among Cameroonian female
university students who should therefore be educated on the advantages of the
black skin and the harmful effects of SW.
PMID- 28412950
TI - Prevalence, withdrawal symptoms and associated factors of khat chewing among
students at Jimma University in Ethiopia.
AB - BACKGROUND: Recently, khat chewing has become a common practice among high
school, college, and university students. Regular khat chewing is thought to be a
predisposing factor for different physical and mental health problems. It can
lead to absenteeism from work and classes. In Ethiopia, to our knowledge no
published study has investigated khat withdrawal symptoms. Therefore, this study
was conducted to determine the prevalence, withdrawal symptoms, and associated
factors of khat chewing among regular undergraduate students on the main campus
of Jimma University in Ethiopia. METHODS: The institution-based, cross-sectional
study was conducted in January 2016. Data were collected from 651 main campus
regular undergraduate students with a structured, self-administered
questionnaire, entered into Epidata 3.1 and exported to SPSS version 20 for
Windows. Bivariate and multivariate logistic regressions were used to explore
associations and identify variables independently associated with khat chewing.
RESULTS: The study found that the lifetime and current prevalence of khat chewing
among students were 26.3% (95% CI: 24.3, 28.3) and 23.9% (95% CI: 21.94, 25.86),
respectively. About 25.7% of students started chewing after joining university,
and 60.5% of these students started during their first year. The main reason
given for starting khat chewing was for study purposes (54.6%), followed by
socialization purposes (42.3%). Among current khat chewers, 72.9% reported that
they had chewed khat for 1 year or more and 68.2% reported that they had
experienced various withdrawal symptoms. The most frequently reported withdrawal
symptoms were feeling depressed, craving, and feeling fatigued. Being male,
attending a place of worship daily/2-3 times per week, cannabis use, smoking
cigarettes, and having family members currently chewing khat were independently
associated with khat chewing. CONCLUSIONS: This study found that large numbers of
university students were currently chewing khat. In this study withdrawal
symptoms and factors that significantly affect khat chewing were identified.
Besides it gave new ideas regarding khat withdrawal symptoms in Ethiopia. It
serves as a critical role of providing information to form rational foundation
for public health policy, prevention and planning to bring change in contributing
factors for Khat chewing. The finding will be serving as base line information
for further study.
PMID- 28412951
TI - Understanding discharge communication behaviours in a pediatric emergency care
context: a mixed methods observation study protocol.
AB - BACKGROUND: One of the most important transitions in the continuum of care for
children is discharge to home. Optimal discharge communication between healthcare
providers and caregivers (e.g., parents or other guardians) who present to the
emergency department (ED) with their children is not well understood. The lack of
policies and considerable variation in practice regarding discharge communication
in pediatric EDs pose a quality and safety risk for children and their parents.
METHODS: The aim of this mixed methods study is to better understand the process
and structure of discharge communication in a pediatric ED context to contribute
to the design and development of discharge communication interventions. We will
use surveys, administrative data and real-time video observation to characterize
discharge communication for six common illness presentations in a pediatric ED:
(1) asthma, (2) bronchiolitis, (3) abdominal pain, (4) fever, (5) diarrhea and
vomiting, and (6) minor head injury. Participants will be recruited from one of
two urban pediatric EDs in Canada. Video recordings will be analyzed using
Observer XT. We will use logistic regression to identify potential demographic
and visit characteristic cofounders and multivariate logistic regression to
examine association between verbal and non-verbal behaviours and parent recall
and comprehension. DISCUSSION: Video recording of discharge communication will
provide an opportunity to capture important data such as temporality, sequence
and non-verbal behaviours that might influence the communication process. Given
the importance of better characterizing discharge communication to identify
potential barriers and enablers, we anticipate that the findings from this study
will contribute to the development of more effective discharge communication
policies and interventions.
PMID- 28412952
TI - Rayleigh-maximum-likelihood bilateral filter for ultrasound image enhancement.
AB - BACKGROUND: Ultrasound imaging plays an important role in computer diagnosis
since it is non-invasive and cost-effective. However, ultrasound images are
inevitably contaminated by noise and speckle during acquisition. Noise and
speckle directly impact the physician to interpret the images and decrease the
accuracy in clinical diagnosis. Denoising method is an important component to
enhance the quality of ultrasound images; however, several limitations discourage
the results because current denoising methods can remove noise while ignoring the
statistical characteristics of speckle and thus undermining the effectiveness of
despeckling, or vice versa. In addition, most existing algorithms do not identify
noise, speckle or edge before removing noise or speckle, and thus they reduce
noise and speckle while blurring edge details. Therefore, it is a challenging
issue for the traditional methods to effectively remove noise and speckle in
ultrasound images while preserving edge details. METHODS: To overcome the above
mentioned limitations, a novel method, called Rayleigh-maximum-likelihood
switching bilateral filter (RSBF) is proposed to enhance ultrasound images by two
steps: noise, speckle and edge detection followed by filtering. Firstly, a sorted
quadrant median vector scheme is utilized to calculate the reference median in a
filtering window in comparison with the central pixel to classify the target
pixel as noise, speckle or noise-free. Subsequently, the noise is removed by a
bilateral filter and the speckle is suppressed by a Rayleigh-maximum-likelihood
filter while the noise-free pixels are kept unchanged. To quantitatively evaluate
the performance of the proposed method, synthetic ultrasound images contaminated
by speckle are simulated by using the speckle model that is subjected to Rayleigh
distribution. Thereafter, the corrupted synthetic images are generated by the
original image multiplied with the Rayleigh distributed speckle of various signal
to noise ratio (SNR) levels and added with Gaussian distributed noise. Meanwhile
clinical breast ultrasound images are used to visually evaluate the effectiveness
of the method. To examine the performance, comparison tests between the proposed
RSBF and six state-of-the-art methods for ultrasound speckle removal are
performed on simulated ultrasound images with various noise and speckle levels.
RESULTS: The results of the proposed RSBF are satisfying since the Gaussian noise
and the Rayleigh speckle are greatly suppressed. The proposed method can improve
the SNRs of the enhanced images to nearly 15 and 13 dB compared with images
corrupted by speckle as well as images contaminated by speckle and noise under
various SNR levels, respectively. The RSBF is effective in enhancing edge while
smoothing the speckle and noise in clinical ultrasound images. In the comparison
experiments, the proposed method demonstrates its superiority in accuracy and
robustness for denoising and edge preserving under various levels of noise and
speckle in terms of visual quality as well as numeric metrics, such as peak
signal to noise ratio, SNR and root mean squared error. CONCLUSIONS: The
experimental results show that the proposed method is effective for removing the
speckle and the background noise in ultrasound images. The main reason is that it
performs a "detect and replace" two-step mechanism. The advantages of the
proposed RBSF lie in two aspects. Firstly, each central pixel is classified as
noise, speckle or noise-free texture according to the absolute difference between
the target pixel and the reference median. Subsequently, the Rayleigh-maximum
likelihood filter and the bilateral filter are switched to eliminate speckle and
noise, respectively, while the noise-free pixels are unaltered. Therefore, it is
implemented with better accuracy and robustness than the traditional methods.
Generally, these traits declare that the proposed RSBF would have significant
clinical application.
PMID- 28412953
TI - Quantification of task-dependent cortical activation evoked by robotic continuous
wrist joint manipulation in chronic hemiparetic stroke.
AB - BACKGROUND: Cortical damage after stroke can drastically impair sensory and motor
function of the upper limb, affecting the execution of activities of daily living
and quality of life. Motor impairment after stroke has been thoroughly studied,
however sensory impairment and its relation to movement control has received less
attention. Integrity of the somatosensory system is essential for feedback
control of human movement, and compromised integrity due to stroke has been
linked to sensory impairment. METHODS: The goal of this study is to assess the
integrity of the somatosensory system in individuals with chronic hemiparetic
stroke with different levels of sensory impairment, through a combination of
robotic joint manipulation and high-density electroencephalogram (EEG). A robotic
wrist manipulator applied continuous periodic disturbances to the affected limb,
providing somatosensory (proprioceptive and tactile) stimulation while
challenging task execution. The integrity of the somatosensory system was
evaluated during passive and active tasks, defined as 'relaxed wrist' and
'maintaining 20% maximum wrist flexion', respectively. The evoked cortical
responses in the EEG were quantified using the power in the averaged responses
and their signal-to-noise ratio. RESULTS: Thirty individuals with chronic
hemiparetic stroke and ten unimpaired individuals without stroke participated in
this study. Participants with stroke were classified as having severe, mild, or
no sensory impairment, based on the Erasmus modification of the Nottingham
Sensory Assessment. Under passive conditions, wrist manipulation resulted in
contralateral cortical responses in unimpaired and chronic stroke participants
with mild and no sensory impairment. In participants with severe sensory
impairment the cortical responses were strongly reduced in amplitude, which
related to anatomical damage. Under active conditions, participants with mild
sensory impairment showed reduced responses compared to the passive condition,
whereas unimpaired and chronic stroke participants without sensory impairment did
not show this reduction. CONCLUSIONS: Robotic continuous joint manipulation
allows studying somatosensory cortical evoked responses during the execution of
meaningful upper limb control tasks. Using such an approach it is possible to
quantitatively assess the integrity of sensory pathways; in the context of
movement control this provides additional information required to develop more
effective neurorehabilitation therapies.
PMID- 28412954
TI - Does a quality improvement campaign accelerate take-up of new evidence? A ten
state cluster-randomized controlled trial of the IHI's Project JOINTS.
AB - BACKGROUND: A decade ago, the Institute for Healthcare Improvement pioneered a
quality improvement (QI) campaign, leveraging organizational and personal social
networks to disseminate new practices. There have been few rigorous studies of
the QI campaign approach. METHODS: Project JOINTS (Joining Organizations IN
Tackling SSIs) engaged a network of state-based organizations and professionals
in a 6-month QI campaign promoting adherence to three new evidence-based
practices known to reduce the risk of infection after joint replacement. We
conducted a cluster-randomized trial including ten states (five campaign states
and five non-campaign states) with 188 hospitals providing joint replacement to
Medicare. We measured adherence to the evidence-based practices before and after
the campaign using a survey of surgical staff and a difference-in-difference
design with multivariable adjustment to compare adherence to each of the relevant
practices and an all-or-none composite measure of the three new practices.
RESULTS: In the campaign states, there were statistically significant increases
in adherence to the three new evidence-based practices promoted by the campaign.
Compared to the non-campaign states, the relative increase in adherence to the
three new practices in the campaign states ranged between 1.9 and 15.9 percentage
points, but only one of these changes (pre-operative nasal screening for
Staphylococcus aureus carriage and decolonization prior to surgery) was
statistically significant (p < 0.05). On the all-or-none composite measure,
adherence to all three evidence-based practices increased from 19.6 to 37.9% in
the campaign states, but declined slightly in the comparison states, yielding a
relative increase of 23 percentage points (p = 0.004). In the non-campaign
states, changes in adherence were not statistically significant. CONCLUSIONS:
Within 6 months, in a cluster-randomized trial, a multi-state campaign targeting
hospitals and professionals involved in surgical care and infection control was
associated with an increase in adherence to evidence-based practices that can
reduce surgical site infection.
PMID- 28412955
TI - Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung
cancer via NF-kappaB/Snail pathway.
AB - BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) play
key roles during multiple cancer processes, such as cell proliferation,
apoptosis, migration and invasion. The previous studies found that NKILA
interacted with and suppressed the nuclear translocation of NF-KappaB, which
influenced metastasis and prognosis in breast cancer. However the clinical
significance and biological role of NKILA in non-small cell lung cancer (NSCLC)
remains unknown. METHODS: We examined expression levels of NKILA in 106 pairs of
NSCLC tissues and cell lines. The expression level of NKILA after TGF-beta1
stimulation also was examined by qRT-PCR and validated by Chromatin
immunoprecipitation (ChIP). Gain-of-function and loss-of-function assays were
performed to examine the effect of NKILA on proliferation, migration and invasion
of NSCLC cells. RNA immunoprecipitation (RIP), western blot and rescue
experiments were carried out to reveal the interrelation between NKILA, NF-kappaB
and EMT signal pathway. RESULTS: The expression of NKILA was down-regulated in
NSCLC cancer tissues compared with matched adjacent noncancerous tissues, and
lower NKILA expression in tumor tissues were significantly correlated with lymph
node metastasis and advanced TNM stage. We found that the expression of NKILA was
mainly regulated by classical TGF-beta signal pathway in NSCLC cells rather than
NF-kappaB pathway reported in breast cancer. Gain and loss of function assays
found that NKILA inhibited migration, invasion and viability of NSCLC cells.
Mechanistic study showed that NKILA attenuated Snail expression via inhibiting
the phosphorylation of IkappaBalpha and NF-kappaB activation, subsequently
suppressed the expression of markers of epithelial-mesenchymal transition
process. CONCLUSIONS: The present study found that the expression of NKILA was
downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC
patients. In vitro studies further clarified that the expression of NKILA was
regulated through classical TGF-beta signal pathway, which subsequently inhibited
migration and invasion of NSCLC cells through interfering NF-kappaB/Snail signal
pathway in NSCLC cells.
PMID- 28412956
TI - Management of suspected common bile duct stones on cholangiogram during same-stay
cholecystectomy for acute gallstone-related disease.
AB - BACKGROUND: Recent data have suggested that upfront cholecystectomy should be
performed even in the presence of moderately abnormal liver function tests
(LFTs). As a consequence, more common bile duct (CBD) stones are discovered on
intra-operative cholangiogram. We assessed the presentation and management of
such patients to refine their management plan. METHODS: Adult patients (>16
years) with an acute gallstone-related disease who had undergone same-stay
cholecystectomy from January 2013 to January 2015 were retrospectively assessed.
We excluded patients with pre-operative endoscopic CBD exploration. RESULTS:
Among the 612 patients with same-stay cholecystectomy, 399 patients were included
in the study, and 213 were excluded because of a pre-operative CBD exploration.
Fifty patients (12.5%) presented an image of CBD stone on the intra-operative
cholangiogram. Such patients were younger (47 vs. 55 years, P = .01) and less
likely to present with fever (1 vs. 11.7%, P = .04) or signs of cholecystitis on
ultrasound (66 vs. 83.7%, P = .003). Admission LFTs were higher in patients with
an image of a stone. Among the 50 patients with an image on cholangiogram, a
stone was confirmed in 26 (52%). Most patients (n = 32) underwent post-operative
assessment with endoscopic ultrasound (EUS). LFTs did not predict the presence of
a confirmed stone. However, the absence of contrast passage into the duodenum was
negatively associated with a confirmed stone (P = .08), and a filling defect was
positively associated with one (P = .11). Most confirmed stones were successfully
extracted by endoscopic retrograde cholangiopancreatogram (ERCP) (25/26, 96%),
except in one patient who needed a per-cutaneous approach because of duodenal
diverticuli. CONCLUSIONS: Same-stay cholecystectomy can (and should) be performed
even in the presence of moderately abnormal liver function tests. The
cholangiogram suspicion of a CBD stone is confirmed in only half of the patients
(more often in the presence of a filling defect, and less often with the absence
of contrast passage). All stones can be safely treated after surgery (most by
ERCP).
PMID- 28412957
TI - Pattern of drug use among preterm neonates: results from an Italian neonatal
intensive care unit.
AB - BACKGROUND: Drug use in preterm neonates admitted to Neonatal Intensive Care Unit
(NICU) has been investigated, so far, in terms of unauthorized or off-label use;
very little is known on the use of combinations of different active substances,
which is frequently required in this population (prophylaxis of infections,
treatment of concomitant diseases). The aim of this study was to describe the
most common patterns of drug use in an Italian NICU, focusing on those with
nephrotoxic potential. METHODS: Medical records of preterm neonates (<37 weeks of
gestational age) weighing less than 1,500 g at birth and admitted to an Italian
NICU were scrutinized in a 3-year retrospective investigation. Analysis included
drug exposure, duration of therapies, co-administration of drugs with potential
renal side effects; also daily protein supplement was calculated from parenteral
nutrition. RESULTS: A cohort of 159 preterm neonates was selected; 68 were born
weighing less than 1,000 g (extremely low birth weight infants, ELBW, Group A),
91 weighed between 1,000 and 1,500 g at birth (Group B). Compared to Group B,
neonates of Group A were more likely to receive pharmacological treatments: the
most used drugs were antibiotics (especially ampicillin and amikacin, p = .07 and
p < .001, respectively), antifungals (especially fluconazole, p < .001), and
diuretics (especially furosemide, p < .001). Analysis of co-administration of
drugs with potential nephrotoxicity showed ampicillin and amikacin as the most
reported combination (94.1% of Group A and 31.9% of Group B), the combination of
furosemide with antibacterials (ampicillin or amikacin) was also frequently
reported, with average period of combination shorter than 2 days. CONCLUSIONS:
ELBW infants were exposed to a higher number of drugs compared to other neonates
and were more likely to receive associations of drugs with nephrotoxic potential
(e.g. furosemide and amikacin), though only for short cycles. Further studies
should evaluate the safety profile (especially potential renal side effects)
related to most commonly used combinations.
PMID- 28412959
TI - Opportunities for developing therapies for rare genetic diseases: focus on gain
of-function and allostery.
AB - BACKGROUND: Advances in next generation sequencing technologies have
revolutionized our ability to discover the causes of rare genetic diseases.
However, developing treatments for these diseases remains challenging. In fact,
when we systematically analyze the US FDA orphan drug list, we find that only 8%
of rare diseases have an FDA-designated drug. Our approach leverages three
primary insights: first, diseases with gain-of-function mutations and late onset
are more likely to have drug options; second, drugs are more often inhibitors
than activators; and third, some disease-causing proteins can be rescued by
allosteric activators in diseases due to loss-of-function mutations. RESULTS: We
have developed a pipeline that combines natural language processing and human
curation to mine promising targets for drug development from the Online Mendelian
Inheritance in Man (OMIM) database. This pipeline targets diseases caused by well
characterized gain-of-function mutations or loss-of-function proteins with known
allosteric activators. Applying this pipeline across thousands of rare genetic
diseases, we discover 34 rare genetic diseases that are promising candidates for
drug development. CONCLUSION: Our analysis has revealed uneven coverage of rare
diseases in the current US FDA orphan drug space. Diseases with gain-of-function
mutations or loss-of-function mutations and known allosteric activators should be
prioritized for drug treatments.
PMID- 28412958
TI - Supporting parents in taking care of their infants admitted to a neonatal
intensive care unit: a prospective cohort pilot study.
AB - BACKGROUND: Family-Centred Care (FCC) is recognized as an important component of
all paediatric care, including neonatal care, although practical clinical
guidelines to support this care model are still needed in Italy. The
characteristics and services for families in Italian NICUs show a lack of
organization and participation. METHODS: The first aim was to compare
satisfaction and stress levels in two groups of parents: an FCC group and a non
FCC group (NFCC). The second aim was to evaluate body weight gain in the newborns
enrolled. This non-randomized, prospective cohort pilot study was conducted in a
single level III NICU at a hospital in Naples, Italy. A cohort of newborns in the
NICU, with their parents were enrolled between March 2014 and April 2015 and they
were divided into two groups: the FCC group (enrolled between October 2014 and
April 2015) remained in the NICU for 8 h a day with FCC model; the NFCC group
(enrolled between March 2014 and September 2014) was granted access to the NICU
for only 1 hour per day. At discharge, both parent groups completed the Parental
Stressor Scale (PSS)-NICU and a questionnaire to assess their satisfaction. In
addition, we compared scores from the mothers and fathers within and between
groups and the body weights of the newborns in the two groups at 60 days.
RESULTS: Parents participating in the FCC group were more satisfied and less
stressed than those in the NFCC group. Infants in the FCC group also showed
increased body weight after 60 days of hospital stay. CONCLUSIONS: Despite our
small population, we confirm that routine adoption of a procedure designed to
apply a FCC model can contribute to improving satisfaction and distress among
preterm infants' parents. Future multi-centre, randomized, controlled trials are
needed to confirm these findings.
PMID- 28412960
TI - A randomised controlled trial to determine the clinical and cost effectiveness of
thulium laser transurethral vaporesection of the prostate (ThuVARP) versus
transurethral resection of the prostate (TURP) in the National Health Service
(NHS) - the UNBLOCS trial: a study protocol for a randomised controlled trial.
AB - BACKGROUND: Transurethral resection of the prostate (TURP) has been the standard
operation for benign prostatic obstruction (BPO) for 40 years, with approximately
25,000 procedures performed annually, and has remained largely unchanged. It is
generally a successful operation, but has well-documented risks for the patient.
Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and
resects the prostate using a surgical technique similar to TURP. The small amount
of study data currently available suggests that ThuVARP may have certain
advantages over TURP, including reduced blood loss and shorter hospital stay,
earlier return to normal activities, and shorter duration of catheterisation.
DESIGN: A multicentre, pragmatic, randomised, controlled, parallel-group trial of
ThuVARP versus standard TURP in men with BPO. Four hundred and ten men suitable
for prostate surgery were randomised to receive either ThuVARP or TURP at four
university teaching hospitals, and three district general hospitals. The key aim
of the trial is to determine whether ThuVARP is equivalent to TURP judged on both
the patient-reported International Prostate Symptom Score (IPSS) and the maximum
urine flow rate (Qmax) at 12 months post-surgery. DISCUSSION: The general
population has an increased life expectancy. As men get older their prostates
enlarge, potentially causing BPO, which often requires surgery. Therefore, as the
population ages, more prostate operations are needed to relieve obstruction.
There is hence sustained interest in the condition and increasing need to find
safer techniques than TURP. Various laser techniques have become available but
none are widely used in the NHS because of lengthy training required for surgeons
or inferior performance on clinical outcomes. Promising initial evidence from one
RCT shows that ThuVARP has equivalent clinical effectiveness when compared to
TURP, as well as other potential advantages. As ThuVARP uses a technique similar
to that used in TURP, the learning curve is short, potentially making it also
very quickly generalisable. This randomised study is designed to provide the high
quality evidence, in an NHS setting, with a range of patient-reported, clinical
and cost-effectiveness outcomes, which will underpin and inform future NICE
guidance. TRIAL REGISTRATION: ISRCTN registry, ISRCTN00788389 . Registered on 20
September 2013.
PMID- 28412961
TI - Perventricular double-device closure of wide-spaced multi-hole perimembranous
ventricular septal defect.
AB - BACKGROUND: Device closure of a wide-spaced multi-hole PmVSD is difficult to
succeed in percutaneous approach. This study is to evaluate the feasibility,
safety and efficacy of perventricular device closure of wide-spaced multi-hole
PmVSD using a double-device implanting technique. METHODS: Sixteen patients with
wide-spaced multi-hole PmVSD underwent perventricular closure with two devices
through an inferior median sternotomy approach under transesophageal
echocardiographic guidance. The largest hole and its adjacent small holes were
occluded with an optimal-sized device. The far-away residual hole was occluded
with the other device using a probe-assisted delivery system. All patients were
followed up for a period of 1 to 4 years to determine the residual shunt,
atrioventricular block and the adjacent valvular function. RESULTS: The number of
the holes of the PmVSD was 2 to 4. The maximum distance between the holes was 5.0
to 10.0 mm (median, 6.4 mm). The diameter of the largest hole was 2.5 to 7.0 mm
(median, 3.6 mm). The success rate of double-device closure was 100%. Immediate
residual shunts were found in 6 patients (38%), and incomplete right bundle
branch block at discharge occurred in 3 cases (19%). Both complications decreased
to 6% at 1-year follow-up. Neither of them had a severe device-related
complication. CONCLUSIONS: Perventricular closure of a wide-spaced multi-hole
PmVSD using a double-device implanting technique is feasible, safe, and
efficacious. In multi-hole PmVSDs with the distance between the holes of more
than 5 mm, double-device implantation may achieve a complete occlusion.
PMID- 28412962
TI - Prospects for malaria control through manipulation of mosquito larval habitats
and olfactory-mediated behavioural responses using plant-derived compounds.
AB - Malaria presents an overwhelming public health challenge, particularly in sub
Saharan Africa where vector favourable conditions and poverty prevail,
potentiating the disease burden. Behavioural variability of malaria vectors poses
a great challenge to existing vector control programmes with insecticide
resistance already acquired to nearly all available chemical compounds. Thus,
approaches incorporating plant-derived compounds to manipulate semiochemical
mediated behaviours through disruption of mosquito olfactory sensory system have
considerably gained interests to interrupt malaria transmission cycle. The
combination of push-pull methods and larval control have the potential to reduce
malaria vector populations, thus minimising the risk of contracting malaria
especially in resource-constrained communities where access to synthetic
insecticides is a challenge. In this review, we have compiled information
regarding the current status of knowledge on manipulation of larval ecology and
chemical-mediated behaviour of adult mosquitoes with plant-derived compounds for
controlling mosquito populations. Further, an update on the current advancements
in technologies to improve longevity and efficiency of these compounds for field
applications has been provided.
PMID- 28412964
TI - MeSH Now: automatic MeSH indexing at PubMed scale via learning to rank.
AB - BACKGROUND: MeSH indexing is the task of assigning relevant MeSH terms based on a
manual reading of scholarly publications by human indexers. The task is highly
important for improving literature retrieval and many other scientific
investigations in biomedical research. Unfortunately, given its manual nature,
the process of MeSH indexing is both time-consuming (new articles are not
immediately indexed until 2 or 3 months later) and costly (approximately ten
dollars per article). In response, automatic indexing by computers has been
previously proposed and attempted but remains challenging. In order to advance
the state of the art in automatic MeSH indexing, a community-wide shared task
called BioASQ was recently organized. METHODS: We propose MeSH Now, an integrated
approach that first uses multiple strategies to generate a combined list of
candidate MeSH terms for a target article. Through a novel learning-to-rank
framework, MeSH Now then ranks the list of candidate terms based on their
relevance to the target article. Finally, MeSH Now selects the highest-ranked
MeSH terms via a post-processing module. RESULTS: We assessed MeSH Now on two
separate benchmarking datasets using traditional precision, recall and F1-score
metrics. In both evaluations, MeSH Now consistently achieved over 0.60 in F
score, ranging from 0.610 to 0.612. Furthermore, additional experiments show that
MeSH Now can be optimized by parallel computing in order to process MEDLINE
documents on a large scale. CONCLUSIONS: We conclude that MeSH Now is a robust
approach with state-of-the-art performance for automatic MeSH indexing and that
MeSH Now is capable of processing PubMed scale documents within a reasonable time
frame. AVAILABILITY: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/MeSHNow/ .
PMID- 28412963
TI - Posttranslationally modified progesterone receptors direct ligand-specific
expression of breast cancer stem cell-associated gene programs.
AB - BACKGROUND: Estrogen and progesterone are potent breast mitogens. In addition to
steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and
progesterone receptor (PR) actions via posttranslational events. Protein kinases
commonly activated in breast cancers phosphorylate steroid hormone receptors
(SRs) and profoundly impact their activities. METHODS: To better understand the
role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs
in 209 human breast tumors represented on 2754 individual tissue spots within a
tissue microarray and assayed the regulation of this site in human tumor explants
cultured ex vivo. To complement this analysis, we assayed PR target gene
regulation in T47D luminal breast cancer models following treatment with
progestin (promegestone; R5020) and antiprogestins (mifepristone, onapristone, or
aglepristone) in conditions under which the receptor is regulated by Lys388
SUMOylation (K388 intact) or is SUMO-deficient (via K388R mutation to mimic
persistent Ser294 phosphorylation). Selected phospho-PR-driven target genes were
validated by qRT-PCR and following RUNX2 shRNA knockdown in breast cancer cell
lines. Primary and secondary mammosphere assays were performed to implicate
phospho-Ser294 PRs, epidermal growth factor signaling, and RUNX2 in breast cancer
stem cell biology. RESULTS: Phospho-Ser294 PR species were abundant in a majority
(54%) of luminal breast tumors, and PR promoter selectivity was exquisitely
sensitive to posttranslational modifications. Phospho-PR expression and target
gene programs were significantly associated with invasive lobular carcinoma
(ILC). Consistent with our finding that activated phospho-PRs undergo rapid
ligand-dependent turnover, unique phospho-PR gene signatures were most prevalent
in breast tumors clinically designated as PR-low to PR-null (luminal B) and
included gene sets associated with cancer stem cell biology (HER2, PAX2, AHR, AR,
RUNX). Validation studies demonstrated a requirement for RUNX2 in the regulation
of selected phospho-PR target genes (SLC37A2). In vitro mammosphere formation
assays support a role for phospho-Ser294-PRs via growth factor (EGF) signaling as
well as RUNX2 as potent drivers of breast cancer stem cell fate. CONCLUSIONS: We
conclude that PR Ser294 phosphorylation is a common event in breast cancer
progression that is required to maintain breast cancer stem cell fate, in part
via cooperation with growth factor-initiated signaling pathways and key phospho
PR target genes including SLC37A2 and RUNX2. Clinical measurement of
phosphorylated PRs should be considered a useful marker of breast tumor stem cell
potential. Alternatively, unique phospho-PR target gene sets may provide useful
tools with which to identify patients likely to respond to selective PR
modulators that block PR Ser294 phosphorylation as part of rational combination
(i.e., with antiestrogens) endocrine therapies designed to durably block breast
cancer recurrence.
PMID- 28412965
TI - Multireceptor fingerprints in progressive supranuclear palsy.
AB - BACKGROUND: Progressive supranuclear palsy (PSP) with a frontal presentation,
characterized by cognitive deficits and behavioral changes, has been recognized
as an early clinical picture, distinct from the classical so-called Richardson
and parkinsonism presentations. The midcingulate cortex is associated with
executive and attention tasks and has consistently been found to be impaired in
imaging studies of patients with PSP. The aim of the present study was to
determine alterations in neurotransmission underlying the pathophysiology of PSP,
as well as their significance for clinically identifiable PSP subgroups. METHODS:
In vitro receptor autoradiography was used to quantify densities of 20 different
receptors in the caudate nucleus and midcingulate area 24' of patients with PSP
(n = 16) and age- and sex-matched control subjects (n = 14). RESULTS: Densities
of gamma-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor
type 2, and N-methyl-D-aspartate receptors were significantly higher in area 24'
of patients with PSP, where tau impairment was stronger than in the caudate
nucleus. Kainate and nicotinic cholinergic receptor densities were significantly
lower, and adenosine receptor type 1 (A1) receptors significantly higher, in the
caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP
subgroups when clinical parameters such as occurrence of frontal presentation and
tau pathology severity were taken into consideration. CONCLUSIONS: We
demonstrate, for the first time to our knowledge, that kainate and A1 receptors
are altered in PSP and that clinically identifiable PSP subgroups differ at the
neurochemical level. Numerous receptors were altered in the midcingulate cortex,
further suggesting that it may prove to be a key region in PSP. Finally, we add
to the evidence that nondopaminergic systems play a role in the pathophysiology
of PSP, thus highlighting potential novel treatment strategies.
PMID- 28412966
TI - TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced
epithelial to mesenchymal transition.
AB - BACKGROUND: The transition between epithelial and mesenchymal phenotypes (EMT)
occurs in a variety of contexts. It is critical for mammalian development and it
is also involved in tumor initiation and progression. Master transcription factor
(TF) regulators of this process are conserved between mouse and human. METHODS:
From a computational analysis of a variety of high-throughput sequencing data
sets we initially inferred that TFAP2A is connected to the core EMT network in
both species. We then analysed publicly available human breast cancer data for
TFAP2A expression and also studied the expression (by mRNA sequencing), activity
(by monitoring the expression of its predicted targets), and binding (by
electrophoretic mobility shift assay and chromatin immunoprecipitation) of this
factor in a mouse mammary gland EMT model system (NMuMG) cell line. RESULTS: We
found that upon induction of EMT, the activity of TFAP2A, reflected in the
expression level of its predicted targets, is up-regulated in a variety of
systems, both murine and human, while TFAP2A's expression is increased in more
"stem-like" cancers. We provide strong evidence for the direct interaction
between the TFAP2A TF and the ZEB2 promoter and we demonstrate that this
interaction affects ZEB2 expression. Overexpression of TFAP2A from an exogenous
construct perturbs EMT, however, in a manner similar to the downregulation of
endogenous TFAP2A that takes place during EMT. CONCLUSIONS: Our study reveals
that TFAP2A is a conserved component of the core network that regulates EMT,
acting as a repressor of many genes, including ZEB2. REVIEWERS: This article has
been reviewed by Dr. Martijn Huynen and Dr. Nicola Aceto.
PMID- 28412967
TI - Factors associated with lingual tonsil hypertrophy in Canadian adults.
AB - BACKGROUND: Hypertrophy of the lingual tonsil tissue in the adult patient is
thought to contribute to the pathophysiology of obstructive sleep apnea. The
underlying etiology of lingual tonsil hypertrophy (LTH) in the adult patient is
unclear and likely multifactorial. Previous studies have suggested that the
lingual tonsils may undergo compensatory hyperplasia post-tonsillectomy in
children, although it is unknown if this occurs or persists into adulthood. The
purpose of this study was to determine what factors are associated with LTH in a
population of Canadian adults. METHODS: Adult patients presenting for
consultation to an academic Rhinology/General Otolaryngology practice were
eligible for enrollment. Demographic data including age, body mass index (BMI),
Reflux Symptom Index (RSI), history of allergy, and history of tonsillectomy was
collected via questionnaire. Endoscopic photographs of the base of tongue and
larynx were captured. These were graded for LTH and Reflux Finding Scale (RFS) by
blinded examiners. Statistical analysis was performed by comparing the mean LTH
value to the variables of interest using two-tailed T-test. P < .05 was
considered significant. RESULTS: One hundred two subjects were enrolled. Age
ranged from 18 to 78. 28 patients had previous tonsillectomy. This was not
associated with a significant increase in lingual tonsil tissue (r = -0.05, p =
0.61). RFS >7 or RSI >13 was considered positive for laryngopharyngeal reflux.
There was no difference in LTH based on RSI positivity (p = 0.44). RFS positivity
correlated with increased lingual tonsil tissue (p < 0.05). BMI >30 was
associated with increased lingual tonsil hypertrophy (p < 0.05). CONCLUSIONS: An
elevated body mass index and positive Reflux Finding Score are associated with
lingual tonsil hypertrophy in adults. Reflux symptom index, history of allergy
and history of childhood tonsillectomy are not associated with LTH.
PMID- 28412968
TI - Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory
and pro-trophic phenotype in vitro.
AB - BACKGROUND: Inflammation is a key contributor to central nervous system (CNS)
injury such as stroke, and is a major target for therapeutic intervention.
Effective treatments for CNS injuries are limited and applicable to only a
minority of patients. Stem cell-based therapies are increasingly considered for
the treatment of CNS disease, because they can be used as in-situ regulators of
inflammation, and improve tissue repair and recovery. One promising option is the
use of bone marrow-derived mesenchymal stem cells (MSCs), which can secrete anti
inflammatory and trophic factors, can migrate towards inflamed and injured sites
or can be implanted locally. Here we tested the hypothesis that pre-treatment
with inflammatory cytokines can prime MSCs towards an anti-inflammatory and pro
trophic phenotype in vitro. METHODS: Human MSCs from three different donors were
cultured in vitro and treated with inflammatory mediators as follows: interleukin
(IL)-1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha) or interferon
gamma. After 24 h of treatment, cell supernatants were analysed by ELISA for
expression of granulocyte-colony stimulating factor (G-CSF), IL-10, brain-derived
neurotrophic factor (BDNF), nerve growth factor (NGF), IL-1 receptor antagonist
(IL-1Ra) and vascular endothelial growth factor (VEGF). To confirm the anti
inflammatory potential of MSCs, immortalised mouse microglial BV2 cells were
treated with bacterial lipopolysaccharide (LPS) and exposed to conditioned media
(CM) of naive or IL-1-primed MSCs, and levels of secreted microglial-derived
inflammatory mediators including TNF-alpha, IL-10, G-CSF and IL-6 were measured
by ELISA. RESULTS: Unstimulated MSCs constitutively expressed anti-inflammatory
cytokines and trophic factors (IL-10, VEGF, BDNF, G-CSF, NGF and IL-1Ra). MSCs
primed with IL-1alpha or IL-1beta showed increased secretion of G-CSF, which was
blocked by IL-1Ra. Furthermore, LPS-treated BV2 cells secreted less inflammatory
and apoptotic markers, and showed increased secretion of the anti-inflammatory IL
10 in response to treatment with CM of IL-1-primed MSCs compared with CM of
unprimed MSCs. CONCLUSIONS: Our results demonstrate that priming MSCs with IL-1
increases expression of trophic factor G-CSF through an IL-1 receptor type 1 (IL
1R1) mechanism, and induces a reduction in the secretion of inflammatory
mediators in LPS-activated microglial cells. The results therefore support the
potential use of preconditioning treatments of stem cells in future therapies.
PMID- 28412969
TI - Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing
protein regulates the proliferation of glioblastoma stem-like cells.
AB - BACKGROUND: Glioblastoma (GBM), a highly aggressive brain tumor, contains a
subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor
maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising
target for GBM treatment. Our group identified the cellular prion protein (PrPC)
and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential
target candidates due to their role in GBM tumorigenesis and in neural stem cell
maintenance. METHODS: GSCs expressing different levels of PrPC were cultured as
neurospheres with growth factors, and characterized with stem cells markers and
adhesion molecules markers through immunofluorescence and flow cytometry. We than
evaluated GSC self-renewal and proliferation by clonal density assays and BrdU
incorporation, respectively, in front of recombinant HOP treatment, combined or
not with a HOP peptide which mimics the PrPC binding site. Stable silencing of
HOP was also performed in parental and/or PrPC-depleted cell populations, and
proliferation in vitro and tumor growth in vivo were evaluated. Migration assays
were performed on laminin-1 pre-coated glass. RESULTS: We observed that, when GBM
cells are cultured as neurospheres, they express specific stemness markers such
as CD133, CD15, Oct4, and SOX2; PrPC is upregulated compared to monolayer culture
and co-localizes with CD133. PrPC silencing downregulates the expression of
molecules associated with cancer stem cells, upregulates markers of cell
differentiation and affects GSC self-renewal, pointing to a pivotal role for PrPC
in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and
self-renewal of GSCs in a PrPC-dependent manner while HOP knockdown disturbs the
proliferation process. In vivo, PrPC and/or HOP knockdown potently inhibits the
growth of subcutaneously implanted glioblastoma cells. In addition, disruption of
the PrPC-HOP complex by a HOP peptide, which mimics the PrPC binding site,
affects GSC self-renewal and proliferation indicating that the HOP-PrPC complex
is required for GSC stemness. Furthermore, PrPC-depleted GSCs downregulate cell
adhesion-related proteins and impair cell migration indicating a putative role
for PrPC in the cell surface stability of cell adhesion molecules and GBM cell
invasiveness, respectively. CONCLUSIONS: In conclusion, our results show that the
modulation of HOP-PrPC engagement or the decrease of PrPC and HOP expression may
represent a potential therapeutic intervention in GBM, regulating glioblastoma
stem-like cell self-renewal, proliferation, and migration.
PMID- 28412970
TI - Membrane potential independent transport of NH3 in the absence of ammonium
permeases in Saccharomyces cerevisiae.
AB - BACKGROUND: Microbial production of nitrogen containing compounds requires a high
uptake flux and assimilation of the N-source (commonly ammonium), which is
generally coupled with ATP consumption and negatively influences the product
yield. In the industrial workhorse Saccharomyces cerevisiae, ammonium (NH4+)
uptake is facilitated by ammonium permeases (Mep1, Mep2 and Mep3), which
transport the NH4+ ion, resulting in ATP expenditure to maintain the
intracellular charge balance and pH by proton export using the plasma membrane
bound H+-ATPase. RESULTS: To decrease the ATP costs for nitrogen assimilation,
the Mep genes were removed, resulting in a strain unable to uptake the NH4+ ion.
Subsequent analysis revealed that growth of this ?mep strain was dependent on the
extracellular NH3 concentrations. Metabolomic analysis revealed a significantly
higher intracellular NHX concentration (3.3-fold) in the ?mep strain than in the
reference strain. Further proteomic analysis revealed significant up-regulation
of vacuolar proteases and genes involved in various stress responses.
CONCLUSIONS: Our results suggest that the uncharged species, NH3, is able to
diffuse into the cell. The measured intracellular/extracellular NHX ratios under
aerobic nitrogen-limiting conditions were consistent with this hypothesis when
NHx compartmentalization was considered. On the other hand, proteomic analysis
indicated a more pronounced N-starvation stress response in the ?mep strain than
in the reference strain, which suggests that the lower biomass yield of the ?mep
strain was related to higher turnover rates of biomass components.
PMID- 28412971
TI - Appraising the holistic value of Lenvatinib for radio-iodine refractory
differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.
AB - BACKGROUND: The objective of the study was to reveal through pragmatic MCDA
(EVIDEM) the contribution of a broad range of criteria to the value of the orphan
drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC)
in country-specific contexts. METHODS: The study was designed to enable
comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current
disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on
the value of lenvatinib was collected from diverse stakeholders during country
specific panels and included: criteria weights (individual and social values);
performance scores (judgments on evidence-collected through MCDA systematic
review); qualitative impacts of contextual criteria; and verbal and written
insights structured by criteria. The value contribution of each criterion was
calculated and uncertainty explored. RESULTS: Comparative effectiveness, Quality
of evidence (Spain and Italy) and Disease severity (France) received the greatest
weights. Four criteria contributed most to the value of lenvatinib, reflecting
its superior Comparative effectiveness (16-22% of value), the severity of RR-DTC
(16-22%), significant unmet needs (14-21%) and robust evidence (14-20%).
Contributions varied by comparator, country and individuals, highlighting the
importance of context and consultation. Results were reproducible at the group
level. Impacts of contextual criteria varied across countries reflecting
different health systems and cultural backgrounds. The MCDA process promoted
sharing stakeholders' knowledge on lenvatinib and insights on context.
CONCLUSIONS: The value of lenvatinib was consistently positive across diverse
therapeutic contexts. MCDA identified the aspects contributing most to value,
revealed rich contextual insights, and helped participants express and explicitly
tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.
PMID- 28412972
TI - Mammary microbiota of dairy ruminants: fact or fiction?
AB - Explorations of how the complex microbial communities that inhabit different body
sites might contribute to health and disease have prompted research on the ways
the harmonious relationship between a host and its microbiota could be used to
keep animals healthy in their production conditions. In particular, there is a
growing interest in the bacterial signatures that can be found in the milk of
healthy or mastitic dairy cows. The concept of sterility of the healthy mammary
gland of dairy ruminants has been challenged by the results of studies using
bacterial DNA-based methodology. The newly obtained data have led to the concept
of the intramammary microbiota composed of a complex community of diverse
bacteria. Accordingly, mammary gland infections are not mere infections by a
bacterial pathogen, but the consequence of mammary dysbiosis. This article
develops the logical implications of this paradigm shift and shows how this
concept is incompatible with current knowledge concerning the innate and adaptive
immune system of the mammary gland of dairy ruminants. It also highlights how the
concept of mammary microbiota clashes with results of experimental infections
induced under controlled conditions or large field experiments that demonstrated
the efficacy of the current mastitis control measures.
PMID- 28412973
TI - Genome-wide DNA methylation measurements in prostate tissues uncovers novel
prostate cancer diagnostic biomarkers and transcription factor binding patterns.
AB - BACKGROUND: Current diagnostic tools for prostate cancer lack specificity and
sensitivity for detecting very early lesions. DNA methylation is a stable genomic
modification that is detectable in peripheral patient fluids such as urine and
blood plasma that could serve as a non-invasive diagnostic biomarker for prostate
cancer. METHODS: We measured genome-wide DNA methylation patterns in 73
clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent
prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array.
We overlaid the most significantly differentially methylated sites in the genome
with transcription factor binding sites measured by the Encyclopedia of DNA
Elements consortium. We used logistic regression and receiver operating
characteristic curves to assess the performance of candidate diagnostic models.
RESULTS: We identified methylation patterns that have a high predictive power for
distinguishing malignant prostate tissue from benign-adjacent prostate tissue,
and these methylation signatures were validated using data from The Cancer Genome
Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding
data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene
regulatory regions with higher DNA methylation in malignant prostate tissues.
CONCLUSIONS: DNA methylation patterns are greatly altered in prostate cancer
tissue in comparison to benign-adjacent tissue. We have discovered patterns of
DNA methylation marks that can distinguish prostate cancers with high specificity
and sensitivity in multiple patient tissue cohorts, and we have identified
transcription factors binding in these differentially methylated regions that may
play important roles in prostate cancer development.
PMID- 28412974
TI - Acute hepatitis B virus infection with delayed appearance of hepatitis B core
antibody in an immunocompromised patient: a case report.
AB - BACKGROUND: Despite the introduction of universal hepatitis B immunization
programs worldwide, outbreaks of acute infection still occur in unimmunized
individuals. A timely diagnosis of hepatitis B is necessary to ensure adequate
clinical care and public health interventions that will reduce transmission. Yet,
interpretation of hepatitis B serological markers can be complex. We present a
case of hepatitis B with atypical markers, including delayed appearance of
hepatitis B core antibody. CASE PRESENTATION: A 62-year-old white woman was
identified as a sexual contact of a male individual with acute hepatitis B virus
infection. She had a history of recurrent low-grade non-Hodgkin lymphoma and had
recently received immunosuppressive therapy. At baseline she had a negative
serology and received three double doses (40 MUg) of Engerix-B vaccine (hepatitis
B vaccine) with a 0-month, 1-month, and 6-month schedule. One month following the
last dose, hepatitis B surface antigen was positive in the absence of hepatitis B
core antibody. The only sign of infection was a slight elevation of alanine
aminotransferase enzymes a few months after first sexual contacts with the male
individual. Hepatitis B virus infection was later confirmed despite the absence
of hepatitis B core antibody. The development of hepatitis B core antibody was
finally noted more than 6 months after the first positive hepatitis B surface
antigen and more than 12 months after elevation of alanine aminotransferase
enzymes. Immunosuppression including rituximab treatment was the most likely
explanation for this serological profile. On her last medical assessment, she had
not developed HBeAg seroconversion despite lower hepatitis B virus
deoxyribonucleic acid levels with tenofovir treatment. CONCLUSIONS: When
confronted with positive hepatitis B surface antigen in the absence of hepatitis
B core antibody, consideration should be given to the possibility of both acute
and persistent infection particularly in the setting of immunosuppression so that
appropriate clinical management and public health interventions can take place.
Given the increasing use of biologicals such as anti-tumor necrosis factor
therapies either alone or with other immunosuppressive agents, this phenomenon
may be encountered more frequently.
PMID- 28412975
TI - Effect of cryopreservation on proliferation and differentiation of periodontal
ligament stem cell sheets.
AB - BACKGROUND: Cryopreservation has been extensively applied to the long-term
storage of a diverse range of biological materials. However, no comprehensive
study is currently available on the cryopreservation of periodontal ligament stem
cell (PDLSC) sheets which have been suggested as excellent transplant materials
for periodontal tissue regeneration. The aim of this study is to investigate the
effect of cryopreservation on the structural integrity and functional viability
of PDLSC sheets. METHODS: PDLSC sheets prepared from extracted human molars were
divided into two groups: the cryopreservation group (cPDLSC sheets) and the
freshly prepared control group (fPDLSC sheets). The cPDLSC sheets were
cryopreserved in a solution consisting of 90% fetal bovine serum and 10% dimethyl
sulfoxide for 3 months. Cell viability and cell proliferation rates of PDLSCs in
both groups were evaluated by cell viability assay and 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide (MTT) assay, respectively. The multilineage
differentiation potentials of the cells were assessed by von Kossa staining and
Oil Red O staining. The chromosomal stability was examined by karyotype analysis.
Moreover, the cell sheets in each group were transplanted subcutaneously into the
dorsal site of nude mice, after which Sirius Red staining was performed to
analyze the efficiency of tissue regeneration. RESULTS: The PDLSCs derived from
both groups of cell sheets showed no significant difference in their viability,
proliferative capacities, and multilineage differentiation potentials, as well as
chromosomal stability. Furthermore, transplantation experiments based on a mouse
model demonstrated that the cPDLSC sheets were equally effective in generating
viable osteoid tissues in vivo as their freshly prepared counterparts. In both
cases, the regenerated tissues showed similar network patterns of bone-like
matrix. CONCLUSIONS: Our results offer convincing evidence that cryopreservation
does not alter the biological properties of PDLSC sheets and could enhance their
clinical utility in tissue regeneration.
PMID- 28412976
TI - Hepatic population derived from human pluripotent stem cells is effectively
increased by selective removal of undifferentiated stem cells using YM155.
AB - BACKGROUND: Pluripotent stem cells (PSCs) such as embryonic stem cells and
induced pluripotent stem cells are promising target cells for cell regenerative
medicine together with recently advanced technology of in-vitro differentiation.
However, residual undifferentiated stem cells (USCs) during in-vitro
differentiation are considered a potential risk for development of cancer cells
and nonspecific lineage cell types. In this study we observed that USCs still
exist during hepatic differentiation, consequently resulting in poor quality of
the hepatic population and forming teratoma in vivo. Therefore, we hypothesized
that effectively removing USCs from in-vitro differentiation could improve the
quality of the hepatic population and guarantee safety from risk of teratoma
formation. METHODS: Human PSCs were differentiated to hepatocytes via four steps.
YM155, a known BIRC5 inhibitor, was applied for removing the residual USCs on the
hepatic differentiation. After YM155 treatment, hepatocyte development was
evaluated by measuring gene expression, immunostaining and hepatic functions at
each stage of differentiation, and forming teratomas were confirmed by cell
transplantation with or without YM155. RESULTS: The selected concentrations of
YM155 removed USCs (NANOG+ and OCT4+) in a dose-dependent manner. As a result,
expression of endodermal markers (SOX17, FOXA2 and CXCR4) at stage II of
differentiation and hepatic markers (ALB, AFP and HNF4A) at stage III was up
regulated by YM155 treatment as well as the hepatic population (ALB+), and
functions (ALB/urea secretion and CYP450 enzyme activity) were enhanced at the
final stage of differentiation (stage IV). Furthermore, we demonstrated that
NANOG and OCT4 expression remaining until stage III (day 15 of differentiation)
completely disappeared when treated with YM155 and teratoma formation was
effectively prevented by YM155 pretreatment in the in-vitro study. CONCLUSIONS:
We suggest that the removal of USCs using YM155 could improve the quantity and
quality of induced hepatocytes and eliminate the potential risk of teratoma
formation.
PMID- 28412977
TI - Noma as a complication of false teeth (Ebiino) extraction: a case report.
AB - BACKGROUND: Ebiino, also known as false tooth extraction, is a traditional
practice done mainly in the remote areas of African countries, including Uganda.
It involves the extraction of tooth buds in babies with common childhood
illnesses such as fever, cough, and diarrhea. It is thought that the tooth buds
are responsible for the ailments seen in these infants. The practice is performed
by traditional healers using unsterile instruments. The complications associated
with this dangerous practice have been mentioned in the literature and include
anemia and septicemia, among others. This case report describes a baby with noma,
an orofacial gangrenous infection. CASE PRESENTATION: A 16-month-old girl from
western Uganda belonging to the Banyankole ethnic group was admitted to Mbarara
University Teaching Hospital with a 5-day history of a dark lesion on the left
cheek. The lesion had started from the left upper gum at the site where a tooth
bud had been extracted 1 week prior to admission. The child had experienced
occasional cough and fever and also had erupting tooth buds. These tooth buds had
been seen as the cause of the cough and fever by the traditional herbalist;
hence, they were extracted. An unsterile instrument had been used for the
procedure. At the hospital, a local examination showed necrotic tissue involving
the left cheek and extending into the left upper gingival area of the girl's
mouth. A clinical diagnosis of orofacial gangrene (noma) was then made.
CONCLUSIONS: Ebiino, or false tooth extraction, is still practiced in some remote
areas of Uganda. Noma has been mentioned as a possible complication of this
traditional practice; however, case reports in the literature are scant. Public
awareness of the dangers of this practice is therefore still required to prevent
this dangerous complication.
PMID- 28412980
TI - Arctic systems in the Quaternary: ecological collision, faunal mosaics and the
consequences of a wobbling climate.
AB - Climate oscillations and episodic processes interact with evolution, ecology and
biogeography to determine the structure and complex mosaic that is the biosphere.
Parasites and parasite-host assemblages are key components in a general
explanatory paradigm for global biodiversity. We explore faunal assembly in the
context of Quaternary time frames of the past 2.6 million years, a period
dominated by episodic shifts in climate. Climate drivers cross a continuum from
geological to contemporary timescales and serve to determine the structure and
distribution of complex biotas. Cycles within cycles are apparent, with drivers
that are layered, multifactorial and complex. These cycles influence the dynamics
and duration of shifts in environmental structure on varying temporal and spatial
scales. An understanding of the dynamics of high-latitude systems, the history of
the Beringian nexus (the intermittent land connection linking Eurasia and North
America) and downstream patterns of diversity depend on teasing apart the
complexity of biotic assembly and persistence. Although climate oscillations have
dominated the Quaternary, contemporary dynamics are driven by tipping points and
shifting balances emerging from anthropogenic forces that are disrupting
ecological structure. Climate change driven by anthropogenic forcing has
supplanted a history of episodic variation and is eliminating ecological barriers
and constraints on development and distribution for pathogen transmission. A
framework to explore interactions of episodic processes on faunal structure and
assembly is the Stockholm Paradigm, which appropriately shifts the focus from
cospeciation to complexity and contingency in explanations of diversity.
PMID- 28412979
TI - Physical exercise for late life depression: effects on cognition and disability.
AB - BACKGROUND: Late-life depression is often associated with cognitive impairments
and disability, which may persist even after adequate antidepressant drug
treatment. Physical exercise is increasingly recognized as an effective
antidepressant agent, and may exert positive effects on these features too.
However, few studies examined this issue, especially by comparing different types
of exercises. METHODS: We performed secondary analyses on data from the Safety
and Efficacy of Exercise for Depression in Seniors study, a trial comparing the
antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non
progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive
aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by
heart rate meters. Patients with late-life depression without severe cognitive
impairment were recruited from primary care and assessed at baseline and 24
weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores)
and Brief Disability Questionnaire. Analyses were based on Generalized Linear
Models. RESULTS: In total, 121 patients (mean age 75, 71% females) were
randomized to the study interventions. Compared with the S group, patients in the
S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect
size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and
disability (p=0.02, effect size=-0.31). Participants in the S+NPE group did not
display significant differences with the control group. CONCLUSIONS: Adding
aerobic, progressive exercise to antidepressant drug treatment may offer
significant advantages over standard treatment for cognitive abilities and
disability. These findings suggest that even among older patients exercise may
constitute a valid therapeutic measure to improve patients' outcomes.
PMID- 28412978
TI - The need for harmonisation and innovation of neuropsychological assessment in
neurodegenerative dementias in Europe: consensus document of the Joint Program
for Neurodegenerative Diseases Working Group.
AB - Cognitive, behavioural, and functional assessment is crucial in longitudinal
studies of neurodegenerative dementias (NDD). Central issues, such as the
definition of the study population (asymptomatic, at risk, or individuals with
dementia), the detection of change/decline, and the assessment of relevant
outcomes depend on quantitative measures of cognitive, behavioural, and
functional status.Currently, we are far from having available reliable protocols
and tools for the assessment of dementias in Europe. The main problems are the
heterogeneity of the tools used across different European countries, the lack of
standardisation of administration and scoring methods across centres, and the
limited information available about the psychometric properties of many tests
currently in widespread use. This situation makes it hard to compare results
across studies carried out in different centres, thus hampering research
progress, in particular towards the contribution to a "big data" common data
set.We present here the results of a project funded by the Joint Program for
Neurodegenerative Diseases (JPND) and by the Italian Ministry of Health. The
project aimed at providing a consensus framework for the harmonisation of
assessment tools to be applied to research in neurodegenerative disorders
affecting cognition across Europe. A panel of European experts reviewed the
current methods of neuropsychological assessment, identified pending issues, and
made recommendations for the harmonisation of neuropsychological assessment of
neurodegenerative dementias in Europe.A consensus was achieved on the general
recommendations to be followed in developing procedures and tools for
neuropsychological assessment, with the aim of harmonising tools and procedures
to achieve more reliable data on the cognitive-behavioural examination. The
results of this study should be considered as a first step to enhancing a common
view and practise on NDD assessment across European countries.
PMID- 28412981
TI - Differences in the use of everyday technology among persons with MCI, SCI and
older adults without known cognitive impairment.
AB - BACKGROUND: To use valid subjective reports sensible to cognitive decline is
vital to identify very early signs of dementia development. Use of everyday
technology (ET) has been shown to be sensitive to differentiate adults with mild
cognitive impairment (MCI) from controls, but the group with subjective cognitive
impairment (SCI) has not yet been examined. This study aims to investigate and
compare self-perceived ability in ET use and number of ETs reported as actually
used in a sample of older adults with SCI, MCI, and older adults with no known
cognitive impairment, i.e. CONTROLS: METHODS: Older adults with MCI (n = 29),
SCI ( n = 26), and controls (n = 30) were interviewed with the short version of
the Everyday Technology Use Questionnaire (S-ETUQ) to capture self-perceived
ability in ET use and number of ETs used. To generate individual measures of
ability to use ET, Rasch analysis was used. The measures were then compared group
wise using ANCOVA. The numbers of ETs used were compared group-wise with ANOVA.
RESULTS: Controls versus SCI and MCI differed significantly regarding ETs
reported as used, but not SCI versus MCI. Similarly, in ability to use ET,
controls versus SCI and MCI differed significantly but not SCI versus MCI.
CONCLUSIONS: The significantly lower numbers of ETs reported as actually used and
the lower ability in SCI and MCI groups compared to controls suggest that ET use
is affected already in very minor cognitive decline. This indicates that self
reported ET use based on the S-ETUQ is sensitive to detect changes already in
SCI.
PMID- 28412982
TI - Social Isolation in Chinese Older Adults: Scoping Review for Age-Friendly
Community Planning.
AB - Chinese older adults may be at increased risk of social isolation and loneliness,
and a fragmented understanding exists about the challenges they face for social
participation in their neighbourhoods and communities. A scoping review was
undertaken to describe the current knowledge on social isolation and loneliness
in urban-dwelling Chinese older adults living in Western societies to inform
future research, practice, and policy in Canada. Nineteen articles met the
inclusion criteria. The World Health Organization's age-friendly community
framework contextualized the study findings. Studies identified issues related to
(1) social participation; (2) community support and health services; (3) housing;
(4) community and information; (5) respect and social inclusion; (6) outdoor
spaces and public buildings; (7) civic participation and employment; and (8)
transportation. Social isolation and loneliness is a growing concern in this
population in Canada, and additional research is needed to identify its scope and
effective interventions.
PMID- 28412984
TI - Facial carbuncle - a new method of conservative surgical management plus
irrigation with antibiotic-containing solution.
AB - OBJECTIVE: This paper reports on a non-conventional method for the management of
facial carbuncles, highlighting its superiority over conventional surgical
treatment in terms of cosmetic outcome and shorter duration of wound healing.
BACKGROUND: The mainstay of treatment for carbuncles involves the early
administration of antibiotics in combination with surgical intervention. The
conventional saucerisation, or incision and drainage, under normal circumstances
results in moderate to large wounds, which may need secondary surgery such as
skin grafting, resulting in a longer duration of wound healing and jeopardising
cosmetic outcome. CASE REPORTS: The reported three cases presented with extensive
carbuncles over the chin, face and lips region. In addition to early commencement
of intravenous antibiotics, the pus was drained, with minimal incision and
conservative wound debridement, with the aim of maximal skin conservation. This
was followed by thrice-daily irrigation with antibiotic-containing solution for a
minimum of 2 consecutive days. The wounds healed within two to four weeks,
without major cosmetic compromise. CONCLUSION: The new method showed superior
cosmetic outcomes, with a shorter duration of wound healing. Conservative
surgical management can be performed under regional anaesthesia, which may reduce
morbidity and mortality; patients with facial carbuncles often have higher risks
with general anaesthesia.
PMID- 28412983
TI - Piezoelectric technology in otolaryngology, and head and neck surgery: a review.
AB - BACKGROUND: Piezoelectric technology has existed for many years as a surgical
tool for precise removal of soft tissue and bone. The existing literature
regarding its use specifically for otolaryngology, and head and neck surgery was
reviewed. METHODS: The databases Medline, the Cochrane Central Register of
Controlled Trials, PubMed, Embase and Cambridge Scientific Abstracts were
searched. Studies were selected and reviewed based on relevance. RESULTS: Sixty
studies were identified and examined for evidence of benefits and disadvantages
of piezoelectric surgery and its application in otolaryngology. The technique was
compared with traditional surgical methods, in terms of intra-operative bleeding,
histology, learning curve, operative time and post-operative pain. CONCLUSION:
Piezoelectric technology has been successfully employed, particularly in otology
and skull base surgery, where its specific advantages versus traditional drills
include a lack of 'blunting' and tissue selectivity. Technical advantages include
ease of use, a short learning curve and improved visibility. Its higher cost
warrants consideration given that clinically significant improvements in
operative time and morbidity have not yet been proven. Further studies may define
the evolving role of piezoelectric surgery in otolaryngology, and head and neck
surgery.
PMID- 28412985
TI - Active surveillance management of head and neck paragangliomas: case series and
review of the literature.
AB - BACKGROUND: Head and neck paragangliomas are rare. They are usually slow-growing,
benign, non-catecholamine secreting tumours, traditionally treated with surgical
excision. Complications of surgical excision include lower cranial nerve palsies,
stroke and death. METHOD: A retrospective case note analysis was conducted of
patients with head and neck paragangliomas treated with a watch-and-scan policy
from March 2003 to September 2015, and the relevant literature was reviewed.
RESULTS: Fifteen head and neck paragangliomas were identified. None of the
patients developed a new lower cranial nerve palsy or progression of their
presenting hearing loss during the follow-up period. Five patients displayed an
increase in maximum linear dimension of 4 mm over an average of 57.4 months. A
review of the literature showed that a watch-and-surveillance scan policy is
evolving as a treatment option for head and neck paragangliomas without malignant
risk factors. CONCLUSION: Readily available surveillance scanning in head and
neck paragangliomas enables the monitoring of head and neck paragangliomas, which
may allow for avoidance of major surgery.
PMID- 28412987
TI - Back pain in the emergency department: Pathological fracture following spinal
manipulation.
AB - Back pain is one of the most common presentations to the emergency department.
Though case reports of patients presenting with increased back pain following
chiropractic spinal manipulations are rare, we have identified a case rarely
reported in the literature where a potential injury from chiropractic
manipulation resulted in a diagnosis of multiple myeloma. We have reported a
previously healthy 66-year-old male who presented with persistent lower back pain
over 4 weeks. An initial evaluation with thoracolumbar radiographs revealed no
significant findings. Following initial presentation to the family physician, the
patient underwent three treatments of spinal manipulation from his local
chiropractor, which resulted in worsening lower back pain. A re-examination and
new radiographs in the hospital revealed multiple compression fractures and an
underlying diagnosis of multiple myeloma. We have explored current literature
examining the prevalence of lower back pain, as well as the incidence of spinal
fracture following chiropractic manipulation, and have highlighted a potential
complication from chiropractic manipulation in a patient with an undiagnosed
underlying neoplastic disorder.
PMID- 28412986
TI - Effects of subacute ingestion of chlorogenic acids on sleep architecture and
energy metabolism through activity of the autonomic nervous system: a randomised,
placebo-controlled, double-blinded cross-over trial.
AB - Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous
consumption of CGA reduces body fat and body weight. Since energy metabolism and
sleep are controlled by common regulatory factors, consumption of CGA might
modulate sleep. Lack of sleep has been identified as a risk factor for obesity,
hypertension and type 2 diabetes. The aim of this study was to determine the
effects of ingesting CGA over 5 d on energy metabolism and sleep quality in
humans. A total of nine healthy subjects (four male and five female) completed a
placebo-controlled, double-blinded, cross-over intervention study. Subjects
consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth
night, subjects stayed in a whole-room metabolic chamber to measure energy
metabolism; sleep was evaluated using polysomnographic recording. It was found
that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0.05) compared
with the control, whereas no effect on sleep architecture, such as slow-wave
sleep, rapid eye movement or waking after sleep onset, was observed. Indirect
calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem
84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h),
P<0.05) but did not affect energy expenditure during sleep. Consumption of CGA
enhanced parasympathetic activity assessed from heart-rate variability during
sleep (999 (sem 77) v. 919 (sem 54), P<0.05). A period of 5-d CGA consumption
significantly increased fat oxidation during sleep, suggesting that beverages
containing CGA may be beneficial to reduce body fat and prevent obesity.
Consumption of CGA shortened sleep latency and did not adversely affect sleep
quality.
PMID- 28412989
TI - Evaluation of methodological aspects of digestibility measurements in ponies fed
different haylage to concentrate ratios.
AB - Methodological aspects of digestibility measurements were studied in four Welsh
pony geldings consuming haylage-based diets with increasing proportions of a
pelleted concentrate according to a 4*4 Latin square design experiment. Ponies
were fed four experimental, iso-energetic (net energy (NE) basis) diets (i.e. 22
MJ NE/day) with increasing proportions of a pelleted concentrate (C) in relation
to haylage (H). The absolute amounts of diet dry matter fed per day were 4.48 kg
of H (100H), 3.36 and 0.73 kg of H and C (75H25C), 2.24 and 1.45 kg of H and C
(50H50C) and 1.12 and 2.17 kg of H and C (25H75C). Diets were supplemented with
minerals, vitamins and TiO2 (3.7 g Ti/day). Voluntary voided faeces were
quantitatively collected daily during 10 consecutive days and analysed for
moisture, ash, ADL, acid-insoluble ash (AIA) and Ti. A minimum faeces collection
period of 6 consecutive days, along with a 14-day period to adapt the animals to
the diets and become accustomed to the collection procedure, is recommended to
obtain accurate estimations on dry matter digestibility and organic matter
digestibility (OMD) in equids fed haylage-based diets supplemented with
concentrate. In addition, the recovery of AIA, ADL and Ti was determined and
evaluated. Mean faecal recovery over 10 consecutive days across diets for AIA,
ADL and Ti was 124.9% (SEM 2.9), 108.7% (SEM 2.0) and 97.5% (SEM 0.9),
respectively. Cumulative faecal recovery of AIA significantly differed between
treatments, indicating that AIA is inadequate to estimate the OMD in equines. In
addition, evaluation of the CV of mean cumulative faecal recoveries obtained by
AIA, ADL and Ti showed greater variations in faecal excretion of AIA (9.1) and
ADL (7.4) than Ti (3.7). The accuracy of prediction of OMD was higher with the
use of Ti than ADL. The use of Ti is preferred as a marker in digestibility
trials in equines fed haylage-based diets supplemented with increasing amounts of
pelleted concentrate.
PMID- 28412990
TI - Influence of pre-storage incubation on hatchability traits, thyroid hormones,
antioxidative status and immunity of newly hatched chicks at two chicken breeder
flock ages.
AB - Egg storage longer than 7 days is associated with negative effects on
hatchability traits. Pre-storage incubation has been a suggested method to reduce
the negative effects of long-term storage times by enhancing the developmental
stage of the embryo and probably reducing the embryonic stress. The objective of
the present study was to investigate the effects of pre-storage incubation and
storage time on hatchability characteristics, chick quality and serum thyroid
hormones, antioxidative properties and immunoglobulin Y (IgY) concentrations of
newly hatched chicks at two breeder flock ages. A total of 8000 fertile eggs were
obtained from two different ages of chicken breeder hens (Egyptian local cross,
Inshas). Half of the eggs were collected from young breeder hens (28 weeks old)
and the other half from old breeder hens (50 weeks old). In each breeder flock
age, eggs were distributed in a completely randomized experimental design in a
2*4 factorial arrangement, with two storage periods (4 or 14 days) and four pre
storage incubation durations (0, 4, 6 or 8 h at 37.5 degrees C). At 28 and 50
weeks of age, pre-storage incubation and its interaction with storage period
influenced significantly the apparent fertility, hatchability of set eggs and
hatchability of fertile eggs and this improvement in hatchability is attributed
to the reduction in embryonic mortality (early, intermediate and late). Pre
storage incubation for 6 or 8 h elevated significantly the grade A chicks and
reduced the grade B chicks in comparison with non-heated controls. Interestingly,
for eggs stored for 14 days, pre-storage incubation for 6 or 8 h enhanced serum
triiodothyronine, thyroxine, glutathione peroxidase activity, total antioxidant
capacity and IgY concentrations significantly and decreased serum malondialdehyde
concentration significantly in the newly hatched chicks. It could be concluded
that pre-storage incubation enhanced the hatching results, improved the
antioxidative properties, reduced lipid peroxidation and elevated the humoral
immunity in the newly hatched chicks. Hence, several benefits might be gained by
pre-storage incubation when fertilized eggs will be stored for long periods.
PMID- 28412991
TI - Inbreeding effects on in vitro embryo production traits in Guzera cattle.
AB - Inbreeding has been associated with the impairment of reproductive performance in
many cattle breeds. Although the usage of reproductive biotechnologies has been
increasing in bovine populations, not much attention has been given to the impact
of inbreeding over cow's performance on artificial reproduction. The objective of
this study was to estimate the impact of inbreeding on in vitro embryo production
in a Guzera breed population. The inbreeding coefficient (F), calculated as half
of the co-ancestry of the individual's parents, was used as an estimate of
inbreeding. The inbreeding coefficients of the donor, sire (used on in vitro
fertilization) and of the embryos were included, separately, in the proposed
models either as classificatory or continuous variables (linear and quadratic
effects). The percentage of non-inbred individuals (or embryos) and mean F of
donors, embryos and sires were 29.38%; 35.76%; 42.86% and 1.98+/-2.68; 1.32+/
3.13; 2.08+/-2.79, respectively. Two different models were considered, one for
oocyte production traits and other for embryo production traits. The increase of
F of the donor significantly (P<0.05) impaired the number of viable oocytes (N
OV), number of grade I oocytes (N GI) and number of cleaved embryos (N CLV).
Moreover, the donor's F influenced the percentage of grade I oocytes (P GI),
percentage of viable embryos (P EMB) and percentage of cleaved embryos that
turned into embryos (P CXE). No significant (P>0.05) effects were observed for
the sire (father of the embryos) inbreeding coefficient over the traits analysed.
Embryo's F influenced (P<0.05) the number of viable embryos (N EMB), percentage
of viable embryos (P EMB) and percentage of cleaved embryos that turn into
embryos (P CXE). Results suggested that an increase in the inbreeding coefficient
might impair the embryos ability to survive through challenges imposed by the in
vitro environment. Submitting highly inbred Guzera female donors to in vitro
embryo production may, in the long-term, have negative implications on the number
of embryos obtained per cow and increase the relative costs of the improvement
programmes based on this technology. High levels of inbreeding should be avoided
when selecting Guzera female donors and planning in vitro fertilization mating.
PMID- 28412992
TI - Acute otitis media associated bilateral sudden hearing loss: case report and
literature review.
AB - BACKGROUND: Sudden sensorineural hearing loss is a rare otological condition with
potential for dire outcomes including permanent hearing loss. Although the
majority of cases are deemed idiopathic, bilateral sudden sensorineural hearing
loss represents a rare subset typically related to systemic conditions, with
higher morbidity and mortality. A controversial association with acute otitis
media has been reported, with few bilateral cases published in the literature.
CASE REPORT: A very rare case of bilateral sudden sensorineural hearing loss
associated with acute otitis media is described, with a review of the literature.
CONCLUSION: The limited evidence available suggests that acute otitis media with
tinnitus and/or bacterial pathology may have an increased risk of sudden
sensorineural hearing loss, which is consistent with the case described. Although
there is no sufficiently powered published evidence to provide definitive
treatment guidelines, the literature reviewed suggests that early myringotomy and
antibiotics may greatly improve treatment outcomes.
PMID- 28412993
TI - Paediatric-onset coronary artery anomalies in pregnancy: a single-centre
experience and systematic literature review.
AB - OBJECTIVES: Individuals with childhood-onset coronary artery anomalies are at
increased risk of lifelong complications. Although pregnancy is thought to confer
additional risk, a few data are available regarding outcomes in this group of
women. We sought to define outcomes of pregnancy in this unique population.
METHODS: We performed a retrospective survey of women with paediatric-onset
coronary anomalies and pregnancy in our institution, combined with a systematic
review of published cases. We defined paediatric-onset coronary artery anomalies
as congenital coronary anomalies and inflammatory arteriopathies of childhood
that cause coronary aneurysms. Major cardiovascular events were defined as
pulmonary oedema, sustained arrhythmia requiring treatment, stroke, myocardial
infarction, cardiac arrest, or death. RESULTS: A total of 25 surveys were mailed,
and 20 were returned (80% response rate). We included 46 articles from the
literature, which described cardiovascular outcomes in 82 women (138
pregnancies). These data were amalgamated for a total of 102 women and 194
pregnancies; 59% of women were known to have paediatric-onset coronary artery
anomalies before pregnancy. In 23%, the anomaly was unmasked during or shortly
after pregnancy. The remainder, 18%, was diagnosed later in life. Major
cardiovascular events occurred in 14 women (14%) and included heart failure (n=5,
5%), myocardial infarction (n=7, 7%), maternal death (n=2, 2%), cardiac arrest
secondary to ventricular fibrillation (n=1, 1%), and stroke (n=1, 1%). The
majority of maternal events (13/14, 93%) occurred in women with no previous
diagnosis of coronary disease. CONCLUSIONS: Women with paediatric-onset coronary
artery anomalies have a 14% risk of adverse cardiovascular events in pregnancy,
indicating the need for careful assessment and close follow-up. Prospective,
multicentre studies are required to better define risk and predictors of
complications during pregnancy.
PMID- 28412994
TI - Effects of high-fat diet on somatic growth, metabolic parameters and function of
peritoneal macrophages of young rats submitted to a maternal low-protein diet.
AB - This study evaluated the effects of a post-weaning high-fat (HF) diet on somatic
growth, food consumption, metabolic parameters, phagocytic rate and nitric oxide
(NO) production of peritoneal macrophages in young rats submitted to a maternal
low-protein (LP) diet. Male Wistar rats (aged 60 d) were divided in two groups (n
22/each) according to their maternal diet during gestation and lactation: control
(C, dams fed 17 % casein) and LP (dams fed 8 % casein). At weaning, half of the
groups were fed HF diet and two more groups were formed (HF and low protein-high
fat (LP-HF)). Somatic growth, food and energy intake, fat depots, serum glucose,
cholesterol and leptin concentrations were evaluated. Phagocytic rate and NO
production were analysed in peritoneal macrophages under stimulation of zymosan
and lipopolysaccharide (LPS)+interferon gamma (IFN-gamma), respectively. The
maternal LP diet altered the somatic parameters of growth and development of
pups. LP and LP-HF pups showed a higher body weight gain and food intake than C
pups. HF and LP-HF pups showed increased retroperitoneal and epididymal fat
depots, serum level of TAG and total cholesterol compared with C and LP pups.
After LPS+IFN-gamma stimulation, LP and LP-HF pups showed reduced NO production
when compared with their pairs. Increased phagocytic activity and NO production
were seen in LP but not LP-HF peritoneal macrophages. However, peritoneal
macrophages of LP pups were hyporesponsive to LPS+IFN-gamma induced NO release,
even after a post-weaning HF diet. Our data demonstrated that there was an
immunomodulation related to dietary fatty acids after the maternal LP diet
induced metabolic programming.
PMID- 28412995
TI - Development and validation of Prediction models for Risks of complications in
Early-onset Pre-eclampsia (PREP): a prospective cohort study.
AB - BACKGROUND: The prognosis of early-onset pre-eclampsia (before 34 weeks'
gestation) is variable. Accurate prediction of complications is required to plan
appropriate management in high-risk women. OBJECTIVE: To develop and validate
prediction models for outcomes in early-onset pre-eclampsia. DESIGN: Prospective
cohort for model development, with validation in two external data sets. SETTING:
Model development: 53 obstetric units in the UK. Model transportability: PIERS
(Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia
TRial Amsterdam) studies. PARTICIPANTS: Pregnant women with early-onset pre
eclampsia. SAMPLE SIZE: Nine hundred and forty-six women in the model development
data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability
(external validation) data sets. PREDICTORS: The predictors were identified from
systematic reviews of tests to predict complications in pre-eclampsia and were
prioritised by Delphi survey. MAIN OUTCOME MEASURES: The primary outcome was the
composite of adverse maternal outcomes established using Delphi surveys. The
secondary outcome was the composite of fetal and neonatal complications.
ANALYSIS: We developed two prediction models: a logistic regression model (PREP
L) to assess the overall risk of any maternal outcome until postnatal discharge
and a survival analysis model (PREP-S) to obtain individual risk estimates at
daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for
overoptimism of predictor effects. For internal validation (of the full models in
the development data) and external validation (of the reduced models in the
transportability data), we computed the ability of the models to discriminate
between those with and without poor outcomes (c-statistic), and the agreement
between predicted and observed risk (calibration slope). RESULTS: The PREP-L
model included maternal age, gestational age at diagnosis, medical history,
systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum
urea concentration, oxygen saturation, baseline treatment with antihypertensive
drugs and administration of magnesium sulphate. The PREP-S model additionally
included exaggerated tendon reflexes and serum alanine aminotransaminase and
creatinine concentration. Both models showed good discrimination for maternal
complications, with anoptimism-adjusted c-statistic of 0.82 [95% confidence
interval (CI) 0.80 to 0.84] for PREP-L and 0.75 (95% CI 0.73 to 0.78) for the
PREP-S model in the internal validation. External validation of the reduced PREP
L model showed good performance with a c-statistic of 0.81 (95% CI 0.77 to 0.85)
in PIERS and 0.75 (95% CI 0.64 to 0.86) in PETRA cohorts for maternal
complications, and calibrated well with slopes of 0.93 (95% CI 0.72 to 1.10) and
0.90 (95% CI 0.48 to 1.32), respectively. In the PIERS data set, the reduced PREP
S model had a c-statistic of 0.71 (95% CI 0.67 to 0.75) and a calibration slope
of 0.67 (95% CI 0.56 to 0.79). Low gestational age at diagnosis, high urine
protein-to-creatinine ratio, increased serum urea concentration, treatment with
antihypertensive drugs, magnesium sulphate, abnormal uterine artery Doppler scan
findings and estimated fetal weight below the 10th centile were associated with
fetal complications. CONCLUSIONS: The PREP-L model provided individualised risk
estimates in early-onset pre-eclampsia to plan management of high- or low-risk
individuals. The PREP-S model has the potential to be used as a triage tool for
risk assessment. The impacts of the model use on outcomes need further
evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40384046.
FUNDING: The National Institute for Health Research Health Technology Assessment
programme.
PMID- 28412996
TI - Laparoscopic surgery versus open resection in patients with gastrointestinal
stromal tumors: An updated systematic review and meta-analysis.
AB - PURPOSES: The contemporary surgery has reported the safety of laparoscopic
surgery (LAP) for patients with gastrointestinal stromal tumors (GISTs). However,
its use is still debated due to suspicion of the oncologic equivalence to open
surgery (OPEN). We conducted a systematic review and meta-analysis of updated
original articles to investigate the short- and long-term clinical outcomes of
LAP compared with OPEN for GISTs. METHODS: A systematic search was performed in
PubMed, Embase, Web of Science, Cochrane Library and CNKI. Comparative studies of
laparoscopic and open surgery for GISTs were published before November 2016. The
Newcastle-Ottawa scale was utilized to conduct quality assessment. The Review
Manager (RevMan) software version 5.0 was used for meta-analysis. RESULTS: Twenty
four studies involving 2140 patients were included for the meta-analysis. The
meta-analysis results showed that, compared with OPEN, LAP indicated potentially
favorable outcomes in terms of operative time (WMD, -30.71; 95% CI, -58.48 to
2.95; P = 0.03); intraoperative blood loss (WMD, -60.90; 95% CI, -91.53 to
30.28; P < 0.0001); time to flatus (WMD, -1.10; 95% CI, -1.41 to -0.79; P <
0.00001); time to oral intake (WMD, -1.25; 95% CI, -1.64 to -0.86; P < 0.00001);
length of hospital stay (WMD, -3.42; 95% CI, -4.37 to -2.46; P < 0.00001);
overall complications (OR, 0.38; 95% CI, 0.27 to 0.54; P < 0.00001); and
recurrence (OR, 0.45; 95% CI, 0.30 to 0.66; P < 0.0001). CONCLUSIONS:
Laparoscopic surgery is safe and feasible for the treatment of GISTs including
less operative time and intraoperative blood loss, earlier postoperative
recovery, shorter hospital stay, and lower rate of overall complications and
recurrence.
PMID- 28412997
TI - Erythematous Lesion on the Nose.
PMID- 28412998
TI - New hPSC-based human models to study pediatric Acute Megakaryoblastic Leukemia
harboring the fusion oncogene RBM15-MKL1.
AB - Pediatric Acute Megakaryoblastic Leukemia not associated to Down Syndrome (non-DS
AMKL) is a rare disease with a dismal prognosis. Around 15% of patients carry the
chromosomal translocation t(1;22) that originates the fusion oncogene RBM15-MKL1,
which is linked to an earlier disease onset (median of 6months of age) and arises
in utero. Here we report the generation of two hPSC cell lines constitutively
expressing the oncogene RBM15-MKL1, resulting in an increased expression of known
RBM15-MKL1 gene targets. These cell lines represent new disease models of
pediatric AMKL to study the impact of the RBM15-MKL1 oncogene on human embryonic
hematopoietic development.
PMID- 28412999
TI - Generation of an induced pluripotent stem cell line from chorionic villi of a
Turner syndrome spontaneous abortion.
AB - A major cause of spontaneous abortions is chromosomal abnormality of foetal
cells. We report the generation of an induced pluripotent stem cell line from the
fibroblasts isolated from chorionic villi of an early spontaneously aborted
foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem
cell line is transgene free, retains the original XO karyotype, expresses
pluripotency markers and undergoes trilineage differentiation. This pluripotent
stem cell model of Turner syndrome should serve as a tool to study the
developmental abnormalities of foetus and placenta that lead to early embryo
lethality and profound symptoms like infertility in 45 XO survivors.
PMID- 28413000
TI - Derivation of mouse embryonic stem cell lines from tyrosine hydroxylase reporter
mice crossed with a human SNCA transgenic mouse model of Parkinson's disease.
AB - Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous
transgenic (tg) mice expressing green fluorescent protein (GFP) under the control
of the rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein
(aSYN) mice expressing human mutant SNCAA53T under the control of the mouse Prion
promoter (MoPrP), or wildtype (WT) mice. The expression of GFP and human aSYN was
validated by immunocytochemistry in midbrain neuron cultures upon differentiation
of mESC lines using stromal cell-derived inducing activity. These mESC lines can
help to study the impact of human aSYN expression in neurons and
oligodendrocytes, and also trace GFP-expressing midbrain neurons.
PMID- 28413001
TI - Development of human induced pluripotent stem cell (iPSC) line from a 60year old
female patient with multiple schwannoma.
AB - Peripheral blood was collected from a clinically diagnosed 60-year old female
patient with multiple schwannoma. Peripheral blood mononuclear cells (PBMCs) were
reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus
reprogramming system. The transgene-free iPSC line showed pluripotency verified
by immunofluorescent staining for pluripotency markers, and the iPSC line was
able to differentiate into the 3 germ layers in vivo. The iPSC line also showed
normal karyotype. This in vitro cellular model will be useful for further
pathological studies of multiple schwannoma.
PMID- 28413002
TI - Characterization of human induced pluripotent stem cell (iPSC) line from a 72year
old male patient with later onset Alzheimer's disease.
AB - Peripheral blood was collected from a clinically diagnosed 72-year old male
patient with later onset Alzheimer's disease. Peripheral blood mononuclear cells
(PBMCs) were reprogrammed with the Yamanaka KMOS reprogramming factors using the
Sendai-virus reprogramming system. The transgene-free iPSC line showed
pluripotency verified by immunofluorescent staining for pluripotency markers, and
the iPSC line was able to differentiate into the 3 germ layers in vivo. The iPSC
line also showed normal karyotype. This in vitro cellular model will be useful
for studying the pathological mechanism of Alzheimer's disease.
PMID- 28413003
TI - Induced pluripotent stem cells derived from a patient with autosomal dominant
familial neurohypophyseal diabetes insipidus caused by a variant in the AVP gene.
AB - Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is
caused by variants in the arginine vasopressin (AVP) gene. Here we report the
generation of induced pluripotent stem cells (iPSCs) from a 42-year-old man
carrying an adFNDI causing variant in exon 1 of the AVP gene using lentivirus
mediated nuclear reprogramming. The iPSCs carried the expected variant in the AVP
gene. Furthermore, the iPSCs expressed pluripotency markers; displayed in vitro
differentiation potential to the three germ layers and had a normal karyotype
consistent with the original fibroblasts. This iPSC line is useful in future
studies focusing on the pathogenesis of adFNDI.
PMID- 28413004
TI - Derivation of human induced pluripotent stem cell (iPSC) line from a 79year old
sporadic male Parkinson's disease patient.
AB - Peripheral blood was collected from a clinically diagnosed 79-year old male
sporadic Parkinson's disease patient. Peripheral blood mononuclear cells (PBMCs)
were reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai
virus reprogramming system. The transgene-free iPSC line showed pluripotency
verified by immunofluorescent staining for pluripotency markers, and the iPSC
line was able to differentiate into the 3 germ layers in vivo. The iPSC line also
showed normal karyotype. This in vitro cellular model can be used to study the
mechanism of sporadic Parkinson's disease and to test new drugs. Resource Table.
PMID- 28413005
TI - Generation of a Nrf2 homozygous knockout human embryonic stem cell line using
CRISPR/Cas9.
AB - Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2) is a well-known
transcription factor that regulates the expression of a large number of anti
oxidant genes in mammalian cells (J.H. Kim et al., 2014). Here, we generated a
homozygous Nrf2 knockout human embryonic stem cell (hESC) line, H9Nrf2KO-A13,
using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell
line maintains pluripotency, differentiation potential into three germ layers,
and a normal karyotype.
PMID- 28413006
TI - Generation of a human induced pluripotent stem cell (iPSC) line from a 64year old
male patient with multiple schwannoma.
AB - Peripheral blood was collected from a clinically diagnosed 64-year old male
multiple schwannoma patient. Peripheral blood mononuclear cells (PBMCs) were
reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus
reprogramming system. The transgene-free iPSC line showed pluripotency verified
by immunofluorescent staining for pluripotency markers, and the iPSC line was
able to differentiate into the 3 germ layers in vivo. The iPSC line also showed
normal karyotype. This in vitro cellular model will be useful for further
pathological studies of multiple schwannoma.
PMID- 28413007
TI - A homozygous Keap1-knockout human embryonic stem cell line generated using
CRISPR/Cas9 mediates gene targeting.
AB - Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that
interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to
the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the
induction of Nrf2-related signaling pathways involving the expression of a set of
anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the
Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic
stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal
morphology, gene expression, and in vivo differentiation potential.
PMID- 28413008
TI - ?
PMID- 28413009
TI - ?
PMID- 28413010
TI - [An example of a network supporting elderly people].
AB - One of a health network's main missions is to favour access to care and to
decompartmentalise the management of patients' treatment. With regard to the
coordination of the pathways of elderly people, the 'Access to Care, Access to
Rights, Health Education' network operating in the Hauts-de-Seine region aims to
support health professionals in establishing and coordinating the health pathway
of people in complex situations. It is a question of trust, cooperation, multi
professionality and exchanges.
PMID- 28413011
TI - [Nurse coordinator and doctor coordinator in a gerontology network].
AB - The Marseille gerontology network consists of a geriatric team providing support
in patients' homes across the Marseille urban area. It forms an integral part of
the geriatric care sector ensuring that elderly people living at home benefit
from a global medical-psychological-social assessment. The aim is to enable
elderly people to continue living and receiving care in their home.
PMID- 28413012
TI - [Identifying frailty and the importance of personalised support].
AB - Over recent years, many hospitals have been looking to promote optimum ageing by
developing a strategy for identifying frailty in elderly people. This raises the
question of prevention in the field of ageing and the capacities to change
behaviour which is harmful to health at any age. Early and long-term support is
essential.
PMID- 28413013
TI - [Adaptation of the home, the occupational therapist's assessment].
AB - When the functional independence of elderly people starts to diminish, the choice
of adapted assistive devices and some simple modifications to the home can allow
them to continue to perform their daily tasks safely and easily. Likewise, when
physical dependency is established, the choice of relevant assistive devices
enables these people to continue living in their home in the right conditions,
both for the person concerned as well as for their direct carers. In these
different situations, the assessment by the occupational therapist enables the
solutions to be adjusted to the capacities, the morphology and the lifestyles of
the elderly person.
PMID- 28413014
TI - [The PASA, a unique place of interconnection].
AB - The PASA, a centre for adapted activities and care, enables nursing homes to
become places of progress and innovation in the management of residents suffering
from Alzheimer's disease and related conditions. The multidisciplinary approach
and the convergence of new perspectives enables some to revive essential threads
of their identity, and others to evolve and build themselves through more
rewarding experiences.
PMID- 28413015
TI - [What to do before a hypervitaminia B12 in the elderly].
AB - Hypervitanimia B12 is an early marker of serious pathologies. These include solid
neoplasms, malignant blood diseases and acute/chronic hepatopathies.
Hypervitaminemia B12 in geriatrics is thereby an indicator in the diagnosis and
prognosis of these conditions.
PMID- 28413016
TI - ?
PMID- 28413017
TI - ?
PMID- 28413020
TI - gammadelta T Cells and B Cells.
AB - gammadelta T cells constitute the third arm of a tripartite adaptive immune
system in jawed vertebrates, besides alphabeta T cells and B cells. Like the
other two lymphocyte-types, they express diverse antigen receptors, capable of
specific ligand recognition. Functionally, gammadelta T cells represent a system
of differentiated subsets, sometimes engaged in cross-regulation, which
ultimately determines their effect on other components of the immune system,
including B cells and antibodies. gammadelta T cells are capable of providing
help to B cells in antibody production. More recently it became clear that
gammadelta T cells influence B cell differentiation during the peripheral stages
of B cell development, control levels of circulating immunoglobulin (all
subclasses), and affect production of autoantibodies. Because of this
relationship between gammadelta T cells and B cells, the extensive variation of
gammadelta T cells among human individuals might be expected to modulate their
humoral responsiveness.
PMID- 28413019
TI - Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with
Both Familial and Sporadic Pituitary Adenomas.
AB - Pituitary adenoma (PA) is one of the most common intracranial neoplasms. Several
genetic predisposing factors for PA have been identified, but they account for a
small portion of cases. In this study, we sought to identify the PA genetic risk
factors by focusing on causative mutations for PAs. Among the 4 affected and 17
asymptomatic members from one family with familial PA, whole-exome sequencing
identified cosegregation of the PA phenotype with the heterozygous missense
mutation c.4136G>T (p.Arg1379Leu) in cadherin-related 23 (CDH23). This mutation
causes an amino acid substitution in the calcium-binding motif of the
extracellular cadherin (EC) domains of CDH23 and is predicted to impair cell-cell
adhesion. Genomic screening in a total of 12 families with familial PA (20
individuals), 125 individuals with sporadic PA, and 260 control individuals
showed that 33% of the families with familial PA (4/12) and 12% of individuals
with sporadic PA (15/125) harbored functional CDH23 variants. In contrast, 0.8%
of the healthy control individuals (2/260) carried functional CDH23 variants.
Gene-based analysis also revealed a significant association between CDH23
genotype and PA (p = 5.54 * 10-7). Moreover, PA individuals who did not harbor
functional CDH23 variants displayed tumors that were larger in size (p = 0.005)
and more invasive (p < 0.001). Therefore, mutations in CDH23 are linked with
familial and sporadic PA and could play important roles in the pathogenesis of
PA.
PMID- 28413018
TI - PLAA Mutations Cause a Lethal Infantile Epileptic Encephalopathy by Disrupting
Ubiquitin-Mediated Endolysosomal Degradation of Synaptic Proteins.
AB - During neurotransmission, synaptic vesicles undergo multiple rounds of exo
endocytosis, involving recycling and/or degradation of synaptic proteins. While
ubiquitin signaling at synapses is essential for neural function, it has been
assumed that synaptic proteostasis requires the ubiquitin-proteasome system
(UPS). We demonstrate here that turnover of synaptic membrane proteins via the
endolysosomal pathway is essential for synaptic function. In both human and
mouse, hypomorphic mutations in the ubiquitin adaptor protein PLAA cause an
infantile-lethal neurodysfunction syndrome with seizures. Resulting from
perturbed endolysosomal degradation, Plaa mutant neurons accumulate K63
polyubiquitylated proteins and synaptic membrane proteins, disrupting synaptic
vesicle recycling and neurotransmission. Through characterization of this
neurological intracellular trafficking disorder, we establish the importance of
ubiquitin-mediated endolysosomal trafficking at the synapse.
PMID- 28413021
TI - Regulation of Innate and Adaptive Immunity by TGFbeta.
AB - Immune regulation by cytokines is crucial in maintaining immune homeostasis,
promoting responses to infection, resolving inflammation, and promoting
immunological memory. Additionally, cytokine responses drive pathology in immune
mediated disease. A crucial cytokine in the regulation of all aspects of an
immune response is transforming growth factor beta (TGFbeta). Although best known
as a crucial regulator of T cell responses, TGFbeta plays a vital role in
regulating responses mediated by virtually every innate and adaptive immune cell,
including dendritic cells, B cells, NK cells, innate lymphoid cells, and
granulocytes. Here, we review our current knowledge of how TGFbeta regulates the
immune system, highlighting the multifunctional nature of TGFbeta and how its
function can change depending on location and context of action.
PMID- 28413024
TI - Tissue-Specific Diversity and Functions of Conventional Dendritic Cells.
AB - Dendritic cells (DCs) are versatile controllers of immunity, which sense
infection or tissue damage and, accordingly, initiate innate and adaptive
effector responses. In recent years, it has become evident that DCs exist as an
independent hematopoietic lineage comprising several developmentally distinct and
functionally specialized subsets that are strategically located in all organs to
defend the organism against invading pathogens. Here, we review the diversity of
DC subtypes found across tissues and discuss our current understanding of the
tissue-specific functions of these cell types.
PMID- 28413023
TI - A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem
Cells to Mature B Lymphocytes.
AB - B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone
marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs)
and sinusoidal endothelial cells. These niches are defined by function and
location: MSPCs are mostly perisinusoidal cells that together with a small subset
of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7),
IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are
morphologically heterogeneous, highly reticular, and form a vast cellular network
in the bone marrow parenchyma capable of interacting with large numbers of
hematopoietic cells. HSCs, downstream multipotent progenitor cells, and common
lymphoid progenitor cells utilize CXCR4 to fine-tune access to critical short
range growth factors provided by MSPCs for their long-term maintenance and/or
multilineage differentiation. In later stages, developing B lymphocytes use CXCR4
to navigate the bone marrow parenchyma, and predominantly cannabinoid receptor-2
for positioning within bone marrow sinusoids, prior to being released into
peripheral blood circulation. In the final stages of differentiation,
transitional B cells migrate to the spleen where they preferentially undergo
further rounds of differentiation until selection into the mature B cell pool
occurs. This bottleneck purges up to 97% of all developing B cells in a
peripheral selection process that is heavily controlled not only by the intensity
of BCR signaling and access to BAFF but also by the proper functioning of the B
cell motility machinery.
PMID- 28413026
TI - The Balance Between Metalloproteinases and TIMPs: Critical Regulator of
Microvascular Endothelial Cell Function in Health and Disease.
AB - Endothelial cells (EC), especially the microvascular EC (MVEC), have critical
functions in health and disease. For example, healthy MVEC provide a barrier
between the fluid and protein found within the blood, and the surrounding tissue.
Following tissue injury or infection, the microvascular barrier is often
disrupted due to activation and dysfunction of the MVEC. Multiple mechanisms
promote MVEC activation and dysfunction, including stimulation by cytokines,
mechanical interaction with activated leukocytes, and exposure to harmful
leukocyte-derived molecules, which collectively result in a loss of MVEC barrier
function. However, MVEC activation is also critical to facilitate recruitment of
inflammatory cells, such as neutrophils (PMNs) and monocytes, into the injured or
infected tissue. Metalloproteinases, including the matrix metalloproteinases
(MMPs) and the closely related, a disintegrin and metalloproteinases (ADAMs),
have been implicated in regulating both MVEC barrier function, through cleavage
of adherens and tight junctions proteins between adjacent MVEC and through
degradation of the extracellular matrix, as well as PMN-MVEC interaction, through
shedding of cell surface PMN receptors. Moreover, the tissue inhibitors of
metalloproteinases (TIMPs), which collectively inhibit most MMPs and ADAMs, are
critical regulators of MVEC activation and dysfunction through their ability to
inhibit metalloproteinases and thereby promote MVEC stability. However, TIMPs
have been also found to modulate MVEC function through metalloproteinase
independent mechanisms, such as regulation of vascular endothelial growth factor
signaling. This chapter is focused on examining the role of the
metalloproteinases and TIMPs in regulation of MVEC function in both health and
disease.
PMID- 28413022
TI - Humanized Immunoglobulin Mice: Models for HIV Vaccine Testing and Studying the
Broadly Neutralizing Antibody Problem.
AB - A vaccine that can effectively prevent HIV-1 transmission remains paramount to
ending the HIV pandemic, but to do so, will likely need to induce broadly
neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving
this goal has been a shortage of animal models with the ability to systematically
pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on
their ability to stimulate bnAb development. Over the past 6 years,
immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs
in mice, an approach that has enabled elucidation of various B-cell tolerance
mechanisms limiting bnAb production and evaluation of strategies to circumvent
such processes. From these studies, in conjunction with the wealth of information
recently obtained regarding the evolutionary pathways and paratopes/epitopes of
multiple bnAbs, it has become clear that the very features of bnAbs desired for
their function will be problematic to elicit by traditional vaccine paradigms,
necessitating more iterative testing of new vaccine concepts. To meet this need,
novel bnAb KI models have now been engineered to express either inferred
prerearranged V(D)J exons (or unrearranged germline V, D, or J segments that can
be assembled into functional rearranged V(D)J exons) encoding predecessors of
mature bnAbs. One encouraging approach that has materialized from studies using
such newer models is sequential administration of immunogens designed to bind
progressively more mature bnAb predecessors. In this review, insights into the
regulation and induction of bnAbs based on the use of KI models will be
discussed, as will new Ig KI approaches for higher-throughput production and/or
altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb
induction studies.
PMID- 28413027
TI - Matrix Metalloproteinases and Platelet Function.
AB - Platelets contain and release several matrix metalloproteinases (MMPs) and their
tissue inhibitors of matrix metalloproteinases (TIMPs), including MMP-1, -2, -3,
9, and -14 and TIMP-1, -2, and -4. Although devoid of a nucleus, platelets also
synthesize TIMP-2 upon activation. Platelet-released MMPs/TIMPs, as well as MMPs
generated by other cells within the cardiovascular system, modulate platelet
function in health and disease. In particular, a normal hemostatic platelet
response to vessel wall injury may be transformed into pathologic thrombus
formation by the release from platelets and/or by the local generation of some
MMPs. Moreover, platelets may localize the production of leukocyte-derived MMPs
to sites of vascular damage, contributing to atherosclerosis development and
complications and to arterial aneurysm formation. Finally, the interaction
between platelets and tumor cells is strongly influenced by MMPs/TIMPs. All these
mechanisms are emerging as important in atherothrombosis, inflammatory disease,
and cancer growth and dissemination. Increasing knowledge of these mechanisms may
open the way to novel therapeutic approaches.
PMID- 28413028
TI - Matrix Metalloproteinases and Leukocyte Activation.
AB - As their name implies, matrix metalloproteinases (MMPs) are thought to degrade
extracellular matrix proteins, a function that is indeed performed by some
members. However, regardless of their cell source, matrix degradation is not the
only function of these enzymes. Rather, individual MMPs have been shown to
regulate specific immune processes, such as leukocyte influx and migration,
antimicrobial activity, macrophage activation, and restoration of barrier
function, typically by processing a range of nonmatrix protein substrates.
Indeed, MMP expression is low under steady-state conditions but is markedly
induced during inflammatory processes including infection, wound healing, and
cancer. Increasing research is showing that MMPs are not just a downstream
consequence of a generalized inflammatory process, but rather are critical
factors in the overall regulation of the pattern, type, and duration of immune
responses. This chapter outlines the role of leukocytes in tissue remodeling and
describes recent progress in our understanding of how MMPs alter leukocyte
activity.
PMID- 28413025
TI - Biochemical and Biological Attributes of Matrix Metalloproteinases.
AB - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
that are involved in the degradation of various proteins in the extracellular
matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic
metalloproteinase domain with catalytic zinc, a hinge region or linker peptide,
and a hemopexin domain. MMPs are commonly classified on the basis of their
substrates and the organization of their structural domains into collagenases,
gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs.
MMPs are secreted by many cells including fibroblasts, vascular smooth muscle
(VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by
activation of their latent zymogen form. MMPs are often secreted as inactive pro
MMP form which is cleaved to the active form by various proteinases including
other MMPs. MMPs cause degradation of ECM proteins such as collagen and elastin,
but could influence endothelial cell function as well as VSM cell migration,
proliferation, Ca2+ signaling, and contraction. MMPs play a role in tissue
remodeling during various physiological processes such as angiogenesis,
embryogenesis, morphogenesis, and wound repair, as well as in pathological
conditions such as myocardial infarction, fibrotic disorders, osteoarthritis, and
cancer. Increases in specific MMPs could play a role in arterial remodeling,
aneurysm formation, venous dilation, and lower extremity venous disorders. MMPs
also play a major role in leukocyte infiltration and tissue inflammation. MMPs
have been detected in cancer, and elevated MMP levels have been associated with
tumor progression and invasiveness. MMPs can be regulated by endogenous tissue
inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines
the extent of ECM protein degradation and tissue remodeling. MMPs have been
proposed as biomarkers for numerous pathological conditions and are being
examined as potential therapeutic targets in various cardiovascular and
musculoskeletal disorders as well as cancer.
PMID- 28413029
TI - Evidence for the Involvement of Matrix-Degrading Metalloproteinases (MMPs) in
Atherosclerosis.
AB - Atherosclerosis leads to blockage of arteries, culminating in myocardial
infarction, and stroke. The involvement of matrix-degrading metalloproteinases
(MMPs) in atherosclerosis is established and many studies have highlighted the
importance of various MMPs in this process. MMPs were first implicated in
atherosclerosis due to their ability to degrade extracellular matrix components,
which can lead to increased plaque instability. However, more recent work has
highlighted a multitude of roles for MMPs in addition to breakdown of
extracellular matrix proteins. MMPs are now known to be involved in various
stages of plaque progression: from initial macrophage infiltration to plaque
rupture. This chapter summarizes the development and progression of
atherosclerotic plaques and the contribution of MMPs. We provide data from human
studies showing the effect of MMP polymorphisms and the expression of MMPs in
both the atherosclerotic plaque and within plasma. We also discuss work in animal
models of atherosclerosis that show the effect of gain or loss of function of
MMPs. Together, the data provided from these studies illustrate that MMPs are
ideal targets as both biomarkers and potential drug therapies for
atherosclerosis.
PMID- 28413030
TI - The Role Matrix Metalloproteinases in the Production of Aortic Aneurysm.
AB - Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of
aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and
abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle
cells in the aortic media and the destruction of extracellular matrix (ECM).
Furthermore, AAA have evidence of inflammation and the cellular elements involved
in inflammation such as macrophages can produce and/or activate MMPs This chapter
focuses on human aortic aneurysm that are not due to specific known genetic
causes because this type of aneurysm is the more common type. This chapter will
also focus on MMP protein expression rather than on genetic data which may not
necessarily translate to increased MMP protein expression. There are supporting
data that certain MMPs are increased in the aortic wall. For TAA, it is most
notably MMP-1, -9, -12, and -14 and MMP-2 when a bicuspid aortic valve is
present. For AAA, it is MMP-1, -2, -3, -9, -12, and -13. The data are weaker or
insufficient for the other MMPs. Several studies of gene polymorphisms support
MMP-9 for TAA and MMP-3 for AAA as potentially important factors. The signaling
pathways in the aorta that can lead to MMP activation include JNK, JAK/stat,
osteopontin, and AMP-activated protein kinase alpha2. Substrates in the human
vasculature for MMP-3, MMP-9, or MMP-14 include collagen, elastin, ECM
glycoprotein, and proteoglycans. Confirmed and potential substrates for MMPs,
maintain aortic size and function so that a reduction in their content relative
to other components of the aortic wall may produce a failure to maintain aortic
size leading to dilatation and aneurysm formation.
PMID- 28413033
TI - Preface.
PMID- 28413034
TI - Preface: Optimizing science impact for effective implementation of Sustainable
Land Management.
PMID- 28413035
TI - Vasa Previa: A Cautious Approach at Caesarean Section.
PMID- 28413031
TI - Matrix Metalloproteinases in Remodeling of Lower Extremity Veins and Chronic
Venous Disease.
AB - The veins of the lower extremity are equipped with efficient wall, contractile
vascular smooth muscle (VSM), and competent valves in order to withstand the high
venous hydrostatic pressure in the lower limb and allow unidirectional movement
of deoxygenated blood toward the heart. The vein wall structure and function are
in part regulated by matrix metalloproteinases (MMPs). MMPs are zinc-dependent
endopeptidases that are secreted as inactive pro-MMPs by different cells in the
venous wall including fibroblasts, VSM, and leukocytes. Pro-MMPs are activated by
other MMPs, proteinases, and other endogenous and exogenous activators. MMPs
degrade various extracellular matrix (ECM) proteins including collagen and
elastin, and could affect other cellular processes including endothelium-mediated
dilation, VSM cell migration, and proliferation as well as modulation of Ca2+
signaling and contraction in VSM. It is thought that increased lower limb venous
hydrostatic pressure increases hypoxia-inducible factors and other MMP inducers
such as extracellular matrix metalloproteinase inducer, leading to increased MMP
expression/activity, ECM protein degradation, vein wall relaxation, and venous
dilation. Vein wall inflammation and leukocyte infiltration cause additional
increases in MMPs, and further vein wall dilation and valve degradation, that
could lead to chronic venous disease and varicose veins (VVs). VVs are often
presented as vein wall dilation and tortuosity, incompetent venous valves, and
venous reflux. Different regions of VVs show different MMP levels and ECM
proteins with atrophic regions showing high MMP levels/activity and little ECM
compared to hypertrophic regions with little or inactive MMPs and abundant ECM.
Treatment of VVs includes compression stockings, venotonics, sclerotherapy, or
surgical removal. However, these approaches do not treat the cause of VVs, and
other lines of treatment may be needed. Modulation of endogenous tissue
inhibitors of metalloproteinases (TIMPs), and exogenous synthetic MMP inhibitors
may provide new approaches in the management of VVs.
PMID- 28413036
TI - ?
PMID- 28413032
TI - Matrix Metalloproteinases in Myocardial Infarction and Heart Failure.
AB - Cardiovascular disease is the leading cause of death, accounting for 600,000
deaths each year in the United States. In addition, heart failure accounts for
37% of health care spending. Matrix metalloproteinases (MMPs) increase after
myocardial infarction (MI) and correlate with left ventricular dysfunction in
heart failure patients. MMPs regulate the remodeling process by facilitating
extracellular matrix turnover and inflammatory signaling. Due to the critical
role MMPs play during cardiac remodeling, there is a need to better understand
the pathophysiological mechanism of MMPs, including the biological function of
the downstream products of MMP proteolysis. Future studies developing new
therapeutic targets that inhibit specific MMP actions to limit the development of
heart failure post-MI are warranted. This chapter focuses on the role of MMPs
post-MI, the efficiency of MMPs as biomarkers for MI or heart failure, and the
future of MMPs and their cleavage products as targets for prevention of post-MI
heart failure.
PMID- 28413037
TI - A Return to Training Days Gone By: A Case for a Uniform Report Card System for
Gynaecologic Surgery.
PMID- 28413038
TI - ?
PMID- 28413039
TI - Excerpts from the World Medical Literature.
PMID- 28413040
TI - ?
PMID- 28413041
TI - Defining Cervical Elongation: A Prospective Observational Study.
AB - OBJECTIVES: Our primary aim was to define cervical elongation (CE) using the
following methods: (1) measurement of pathology specimen, (2) physician
perception, (3) intraoperative estimate of anterior cervical length, and (4)
office Pelvic Organ Prolapse Quantification (POP-Q) points C and D. Our secondary
aim was to determine whether these definitions correlate with perioperative
outcomes. METHODS: Women undergoing vaginal hysterectomy and prolapse repair were
enrolled. Office POP-Q measurements were collected. Estimates of cervical length
were made based on points C minus D of the POP-Q and by manual exam using the
surgeon's index and middle fingers. Cervical dimensions were measured from the
pathology specimen at the end of the case. CE was defined as one standard
deviation (SD) above the mean for each definition. Additional intraoperative data
was collected to determine the surgeon perception of cervical anatomy. RESULTS: A
total of 90 patients were enrolled during the study period. Our definitions for
CE were as follows: (1) 5 cm (70 without and 20 with CE), (2) physician
perception (67 without and 23 with CE), (3) 3.4 cm (79 without and 11 with CE),
and (4) 8.3 cm (77 without and 13 with CE). After controlling for uterine weight
and the presence of fibroids, the operative time was the only outcome measure
that remained elevated for patients with CE using our first definition (42.4 +/-
20.1 without vs. 53.8 +/- 19.2 with CE, P = 0.03). CONCLUSIONS: CE using our
first definition was associated with a statistically significant increase in
operative time in women undergoing hysterectomy at the time of prolapse repair.
PMID- 28413042
TI - No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal
Contraception.
AB - OBJECTIVE: To provide guidelines for health care providers on the use of
contraceptive methods to prevent pregnancy and on the promotion of healthy
sexuality. OUTCOMES: Overall efficacy of cited contraceptive methods, assessing
reduction in pregnancy rate, safety, and side effects; the effect of cited
contraceptive methods on sexual health and general well-being; and the
availability of cited contraceptive methods in Canada. EVIDENCE: Medline and the
Cochrane Database were searched for articles in English on subjects related to
contraception, sexuality, and sexual health from January 1994 to December 2015 in
order to update the Canadian Contraception Consensus published February-April
2004. Relevant Canadian government publications and position papers from
appropriate health and family planning organizations were also reviewed. VALUES:
The quality of the evidence is rated using the criteria described in the Report
of the Canadian Task Force on Preventive Health Care. Recommendations for
practice are ranked according to the method described in this report. SUMMARY
STATEMENTS: RECOMMENDATIONS.
PMID- 28413043
TI - ?
AB - OBJECTIF: Mettre a la disposition des fournisseurs de soins des lignes
directrices concernant le recours a des methodes contraceptives pour prevenir la
grossesse et la promotion d'une sexualite saine. ISSUES: Efficacite globale des
methodes contraceptives citees : evaluation de l'innocuite, des effets
indesirables et de la baisse du taux de grossesse; effet des methodes
contraceptives citees sur la sante sexuelle et le bien-etre general;
disponibilite des methodes contraceptives citees au Canada. ReSULTATS: Des
recherches ont ete effectuees dans MEDLINE et la base de donnees Cochrane afin
d'en tirer les articles en anglais publies entre janvier 1994 et decembre 2015
traitant de sujets lies a la contraception, a la sexualite et a la sante
sexuelle, dans le but de mettre a jour le consensus canadien sur la contraception
paru de fevrier a avril 2004. Nous avons egalement passe en revue les
publications pertinentes du gouvernement canadien, ainsi que les declarations de
principes issues d'organisations competentes vouees a la sante et a la
planification familiale. VALEURS: La qualite des resultats a ete evaluee au moyen
des criteres decrits par le Groupe d'etude canadien sur les soins de sante
preventifs. Les recommandations quant a la pratique sont classees en fonction de
la methode decrite dans le rapport du Groupe. DeCLARATIONS SOMMAIRES:
RECOMMANDATIONS.
PMID- 28413044
TI - Expression profiling feline peripheral blood monocytes identifies a
transcriptional signature associated with type two diabetes mellitus.
AB - Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes
(T2D) in humans, especially with respect to the role of obesity-induced insulin
resistance, glucose toxicity, decreased number of pancreatic beta-cells and
pancreatic amyloid deposition. Cats have thus been proposed as a valuable
translational model of T2D. In humans, inflammation associated with adipose
tissue is believed to be central to T2D development, and peripheral blood
monocytes (PBM) are important in the inflammatory cascade which leads to insulin
resistance and beta-cell failure. PBM may thus provide a useful window to study
the pathogenesis of diabetes mellitus in cats, however feline monocytes are
poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to
profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with
normal glucose tolerance. Feline monocytes were enriched for genes expressed in
human monocytes, and, despite heterogeneous gene expression, we identified a T2D
associated expression signature associated with cell cycle perturbations, DNA
repair and the unfolded protein response, oxidative phosphorylation and
inflammatory responses. Our data provide novel insights into the feline monocyte
transcriptome, and support the hypothesis that inflammatory monocytes contribute
to T2D pathogenesis in cats as well as in humans.
PMID- 28413045
TI - Effector mechanisms of humoral immunity to porcine reproductive and respiratory
syndrome virus.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) continues to afflict
swine nearly 30 years after it was first discovered as the causative agent of
"mystery swine disease". Immunological tools of vaccination and exposure to
virulent viruses have not succeeded in achieving control and prevention of PRRSV.
Humoral immunity, mediated by antibodies, is a hallmark of anti-viral immunity,
but little is known about the effector mechanisms of humoral immunity against
PRRSV. It is essential to understand the immunological significance of antibody
functions, including recently described broadly neutralizing antibodies and
potential non-neutralizing activities, in the immune response to PRRSV. Here, we
review recent research from PRRSV and other host-pathogen interactions to inform
novel routes of exploration into PRRSV humoral immunity which may be important
for identifying the immunological correlates of protection against PRRSV
infection.
PMID- 28413046
TI - Heat stress decreases expression of the cytokines, avian beta-defensins 4 and 6
and Toll-like receptor 2 in broiler chickens infected with Salmonella
Enteritidis.
AB - A high ambient temperature is a highly relevant stressor in poultry production.
Heat stress (HS) has been reported to reduce animal welfare, performance indices
and increase Salmonella susceptibility. Salmonella spp. are major zoonotic
pathogen that cause over 1 billion of human infections worldwide annually.
Therefore, the current study was designed to analyze the effect of heat stress on
Salmonella infection in chickens through modulation of the immune responses.
Salmonella Enteritidis was inoculated via gavage at one day of age (106cfu/mL).
Heat stress 31+/-1 degrees C was applied from 35 to 41 days of age. Broiler
chickens were divided into the following groups of 12 chickens: control (C); heat
stress (HS31 degrees C); S. Enteritidis positive control (PC); and S.
Enteritidis+heat stress (PHS31 degrees C). We observed that heat stress increased
corticosterone serum levels. Concomitantly heat stress decreased (1) the IgA and
IFN-gamma plasmatic levels; (2) the mRNA expression of IL-6, IL-12 in spleen and
IL-1beta, IL-10, TGF-beta in cecal tonsils; (3) the mRNA expression of AvBD4 and
AvBD6 in cecal tonsils; and (4) the mRNA expression of TLR2 in spleen and cecal
tonsils of chickens infected with S. Enteritidis (PHS31 degrees C group). Heat
stress also increased Salmonella colonization in the crop and caecum as well as
Salmonella invasion to the spleen, liver and bone marrow, showing a deficiency in
the control of S. Enteritidis induced infection. Together, the present data
suggested that heat stress activated hypothalamus-pituitary-adrenal (HPA) axis,
as observed by the increase in the corticosterone levels, which in turn
presumably decreases the immune system activity, leading to an impairment of the
intestinal mucosal barrier and increasing chicken susceptibility to the invasion
of different organs by S. Enteritidis .
PMID- 28413047
TI - A homolog of teleostean signal transducer and activator of transcription 3
(STAT3) from rock bream, Oplegnathus fasciatus: Structural insights,
transcriptional modulation, and subcellular localization.
AB - Signal transducer and activator of transcription 3 (STAT3) is one of the crucial
transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it
was previously considered as acute phase response factor. A number of
interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to
be involved in activation of STAT3. In addition, various growth factors and
pathogenic or oxidative stresses mediate the activation of a wide range of
functions via STAT3. In this study, a STAT3 homolog was identified and
functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus. In
silico characterization revealed that the RbSTAT3 amino acid sequence shares
highly conserved common domain architectural features including N-terminal
domain, coiled coil domain, DNA binding domain, linker domain, and Src homology 2
(SH2) domains. In addition, a fairly conserved transcriptional activation domain
(TAD) was located at the C-terminus. Comparison of RbSTAT3 with other
counterparts revealed higher identities (>90%) with fish orthologs. The genomic
sequence of RbSTAT3 was obtained from a bacterial artificial chromosome (BAC)
library, and was identified as a multi-exonic gene (24 exons), as found in other
vertebrates. Genomic structural comparison and phylogenetic studies have showed
that the evolutionary routes of teleostean and non-teleostean vertebrates were
distinct. Quantitative real time PCR (qPCR) analysis revealed that the spatial
distribution of RbSTAT3 mRNA expression was ubiquitous and highly detectable in
blood, heart, and liver tissues. Transcriptional modulation of RbSTAT3 was
examined in blood and liver tissues after challenges with bacteria (Edwardsiella
tarda and Streptococcus iniae), rock bream irido virus (RBIV), and immune
stimulants (LPS and poly (I:C)). Significant changes in RbSTAT3 transcription
were also observed in response to tissue injury. In addition, the transcriptional
up-regulation of RbSTAT3 was detected in rock bream heart cells upon recombinant
rock bream IL-10 (rRbIL-10) treatment. Subcellular localization and nuclear
translocation of rock bream STAT3 following poly (I:C) treatment were also
demonstrated. Taken together, the results of the current study provide important
evidence for potential roles of rock bream STAT3 in the immune system and wound
healing processes.
PMID- 28413048
TI - Milk C-reactive protein in canine mastitis.
AB - Presence of mastitis in lactating bitches can become life threatening for both
the bitch and pups. The aim of the present study was to evaluate a possible
utility of C-reactive protein (CRP) in both milk and serum for canine mastitis
diagnosis. Our study showed that milk CRP levels ranged between 0.1 and 4.9MUg/mL
and from 0.3 to 40.0MUg/mL in healthy and diseased bitches (P<0.01),
respectively, while serum CRP levels ranged between 2.0 and 8.6MUg/mL and between
0.3 and 162.3MUg/mL in healthy and diseased bitches (P<0.01), respectively. Milk
and serum CRP levels were higher in both clinical and subclinical mastitis when
compared with healthy controls (P<0.05 in all cases). However, no significant
differences were recorded in CRP concentrations between clinical and subclinical
cases. Based on these results, it could be concluded that serum and milk CRP
could be useful in order to diagnose canine mastitis.
PMID- 28413049
TI - Evaluation of blood T-lymphocyte subpopulations involved in host cellular
immunity in dogs with mammary cancer.
AB - Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other
cancers, various alterations in blood cell populations involved in host cellular
immunity have been reported; among these cell populations some T-lymphocyte
subsets play an important role against cancer. The purpose of the present study
was to investigate any alterations in circulating T-lymphocyte subpopulations
involved in cellular immunity in bitches with mammary cancer, in comparison to
age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14
control dogs were included in this study. Twelve out of the 28 bitches had
mammary cancer of clinical stage II and 16/28 of stage III. Histological
examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28
carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers
were measured by complete blood count. Furthermore, blood T-lymphocyte population
(CD3+) and the subpopulations CD4+, CD8+ and CD5low+ were assessed by flow
cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers
were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls.
Flow cytometric analysis revealed that the relative percentage of T-lymphocytes
(CD3+) and of CD4+, CD8+ subpopulations was lower (the CD4+/CD8+ ratio was
higher), whereas the percentage of CD5low+ T-cells was higher, in dogs with
cancer compared to controls; however, a statistically significant difference was
found only in the case of CD8+ T-cells (P=0.014), whereas in the case of the
CD4+/CD8+ ratio the difference almost reached statistical significance (P=0.059).
Based on these findings, it can be suggested that, although the absolute number
of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte
subpopulations involved in host cell-mediated immunity are altered, but only
cytotoxic CD8+ T-cells are significantly suppressed, in dogs with mammary cancer
of clinical stage II or III compared to age-matched healthy controls.
PMID- 28413050
TI - Toll-like receptor 2 gene polymorphisms in Chinese Holstein cattle and their
associations with bovine tuberculosis.
AB - This study evaluated whether there was an association between polymorphisms
within the Toll-like receptor 2 gene (TLR2) of Chinese Holstein cattle and
susceptibility to bovine tuberculosis (BTB). In a case-control study including
210 BTB cases and 237 control cattle, we found only two common single-nucleotide
polymorphisms (SNPs) within the entire coding region of the TLR2 gene, A631G
(rs95214857) and T1707C (rs1388116488). Additionally, the allele and genotype
distributions of A631G and T1707C were not different between case and control
groups, indicated that these SNPs were not associated with susceptibility to BTB.
These results suggested that polymorphisms in the TLR2 gene might not play a
significant role in the BTB risk in Chinese Holstein cattle.
PMID- 28413051
TI - Protective efficacy of a novel recombinant Marek's disease virus vector vaccine
against infectious bursal disease in chickens with or without maternal
antibodies.
AB - Infectious bursal disease (IBD) causes significant clinical and economic losses
to the poultry industry worldwide. Current vaccine programs using live attenuated
and inactivated vaccines have numerous drawbacks. As an alternative solution to
control IBD, a Marek's disease virus (MDV) vector vaccine (rMDV-VP2) expressing
the VP2 gene of infectious bursal disease virus (IBDV) has been developed. In
this study, the protective efficacy of rMDV-VP2 was evaluated in a dose-related
experiment which showed that a single dose of 1000 PFU was sufficient to fully
protect chickens against IBDV infection. Chickens inoculated with lower doses of
rMDV-VP2 (250 or 500 PFU) conferred 80 and 90% protection against IBDV. Next,
rMDV-VP2 vaccine provided 90% protection against IBDV in commercial layer
chickens with maternal antibodies, which was higher than the protective efficacy
using the B87 live vaccine of IBDV. Additionally, rMDV-VP2 conferred effective
protection against very virulent MDV challenge in chickens (95% for chickens
vaccinated with 250 or 500 PFU and 100% for chickens vaccinated with 1000 or 2000
PFU). These results demonstrated that rMDV-VP2 may be a novel bivalent vaccine
against IBD and Marek's disease in chickens.
PMID- 28413052
TI - Purified natural pig immunoglobulins can substitute dietary zinc in reducing
piglet post weaning diarrhoea.
AB - Enteric infectious disease in weaner piglets, including postweaning diarrhoea
(PWD), are usually treated and/or prevented with antibiotics and/or zinc oxide in
the piglet feed. However extensive use of antibiotics and zinc oxide in intensive
animal production is unwanted as it may promote microbial antibiotic resistance
and pose environmental problems. Recently, in an experimental model of PWD, we
observed that oral administration of purified porcine immunoglobulin G (ppIgG)
from pooled natural pig plasma could reduce enteric infection. In the present
study we were able to reproduce these results as it was observed that oral ppIgG
accelerated clearance of faecal haemolytic bacteria in pigs challenged with E.
coli in comparison with pigs not receiving ppIgG. This effect was observed upon
feeding ppIgG for seven days postweaning suggesting that ppIgG does not have to
be used prophylactically for several days preweaning. Furthermore, the effect of
oral administration of ppIgG for seven days postweaning was equal to or better
than that of dietary zinc oxide in reducing diarrhoea symptoms and in clearing
faecal haemolytic bacteria for 14days postweaning. These observations warrant
future trials of dietary ppIgG in intensive swine production units to establish
its performance as an alternative to dietary antibiotics and zinc oxide for
preventing PWD.
PMID- 28413053
TI - Introduction.
PMID- 28413054
TI - Corrigendum to "Evidence of substantial development of inhibitory control and
sustained attention between 6 and 8years of age on an unpredictable Go/No-Go
task" [J. Exp. Child Psychol. 157 (2017) 66-80].
PMID- 28413055
TI - Functional Genomics and High Content Screening in the Nervous System.
PMID- 28413056
TI - Impact of scalp location on survival in head and neck melanoma: A retrospective
cohort study.
AB - BACKGROUND: Scalp melanomas have more aggressive clinicopathological features
than other melanomas and mortality rates more than twice that of melanoma located
elsewhere. OBJECTIVE: We sought to describe the survival of patients with scalp
melanoma versus other cutaneous head and neck melanoma (CHNM), and explore a
possible independent negative impact of scalp location on CHNM survival. METHODS:
A retrospective cohort study was performed of all invasive primary CHNM cases
seen at a tertiary referral center over a 20-year period. Melanoma-specific
survival (MSS) was compared between scalp melanoma and other invasive CHNM.
Multivariable Cox proportional hazards regression was performed to determine
associations with survival. RESULTS: On univariate analysis, patients with scalp
melanoma had worse MSS than other CHNM (hazard ratio 2.22, 95% confidence
interval 1.59-3.11). Scalp location was not associated with MSS in CHNM on
multivariable analysis (hazard ratio 1.11, 95% confidence interval 0.77-1.61) for
all tumors together, but remained independently associated with MSS for the 0.76-
to 1.50-mm thickness stratum (hazard ratio 5.51, 95% confidence interval 1.55
19.59). LIMITATIONS: Disease recurrence was not assessed because of unavailable
data. CONCLUSION: The poorer survival of scalp melanoma is largely explained by
greater Breslow thickness and a higher proportion of male patients.
PMID- 28413058
TI - Erythromelalgia: Identification of a corticosteroid-responsive subset.
AB - BACKGROUND: Corticosteroids (CS) may benefit certain patients with
erythromelalgia. OBJECTIVES: Our objective was to determine clinical predictors
of corticosteroid-responsive erythromelalgia. METHODS: Patients with
erythromelalgia who received CS were identified and stratified into
corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs),
complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs +
CSRs). In the study variable analysis, P < .05 was considered statistically
significant. RESULTS: The median (interquartile range) age of the 31-patient
cohort was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were
NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to
disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%)
were SRs (P = .003; odds ratio [OR] = 0.069 [95% confidence interval {CI}, 0.011
0.431]). Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or
infection; P = .007; OR = 12.667 [95% CI, 2-80.142]). SR patients received CS
sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS
trial (>=200 mg prednisone cumulatively) was administered to 17 (55%) patients,
of whom 13 (76%) were SRs (P = .012; OR = 8.125 [95% CI, 1.612-40.752]).
LIMITATIONS: This was a retrospective case series. CONCLUSION: An infectious,
traumatic, or surgical precipitant and subacute presentation may portend CR
erythromelalgia. A transient "golden window" where CS intervention is useful may
exist before irreversible nociceptive remodeling and central sensitization
occurs.
PMID- 28413057
TI - Sex differences in the association of cutaneous melanoma incidence rates and
geographic ultraviolet light exposure.
AB - BACKGROUND: Cutaneous melanoma (CM) incidence rates continue to increase, and the
reasons are unknown. Previously, we reported a unique age-specific sex difference
in melanoma that suggested additional causes other than solar ultraviolet (UV)
radiation. OBJECTIVE: This study attempted to understand whether and how UV
radiation differentially impacts the CM incidence in men and women. METHODS: CM
data and daily UV index (UVI) from 31 cancer registries were collected for
association analysis. A second dataset from 42 US states was used for validation.
RESULTS: There was no association between log-transformed female CM rates and
levels of UVI, but there was a significant association between male rates and UVI
and a significant association between overall rates and UVI. The 5-year age
specific rate-UVI association levels (represented by Pearson's coefficient rho)
increased with age in men, but age-specific rho levels remained low and unchanged
in women. The significant rate-UVI association in men and nonassociation in women
was validated in a population of white residents of the United States.
LIMITATIONS: Confounders, including temperature and latitude, are difficult to
separate from UVI. CONCLUSIONS: Ambient UVI appears to be associated with
melanoma incidence in males but not in females.
PMID- 28413059
TI - Viral exanthems: An update on laboratory testing of the adult patient.
AB - Although classic viral exanthems of childhood are well described, they are rarely
differentiated in adults. Laboratory techniques for viral identification have
advanced without substantial literature to suggest how a dermatologist ought to
conduct a cost-effective and diagnostic viral panel. Certain clinical features
such as petechiae, vesicles, and dusky macular or morbilliform exanthems point
strongly toward a viral exanthem. Differentiation of drug and viral causes of
morbilliform eruptions has proven difficult. It is possible that with further
diagnostic refinement that unnecessary and fruitless workups of an exanthem and
unneeded discontinuation of drugs can be avoided. We review viral exanthems based
on clinical features and discuss the available and optimal laboratory techniques
to assist the dermatologist in a targeted workup.
PMID- 28413060
TI - Stuttering treatment and brain research in adults: A still unfolding
relationship.
AB - PURPOSE: Brain imaging and brain stimulation procedures have now been used for
more than two decades to investigate the neural systems that contribute to the
occurrence of stuttering in adults, and to identify processes that might enhance
recovery from stuttering. The purpose of this paper is to review the extent to
which these dual lines of research with adults who stutter have intersected and
whether they are contributing towards the alleviation of this impairment. METHOD:
Several areas of research are reviewed in order to determine whether research on
the neurology of stuttering is showing any potential for advancing the treatment
of this communication disorder: (a) attempts to discover the neurology of
stuttering, (b) neural changes associated with treated recovery, and (c) direct
neural intervention. RESULTS AND CONCLUSIONS: Although much has been learned
about the neural underpinnings of stuttering, little research in any of the
reviewed areas has thus far contributed to the advancement of stuttering
treatment. Much of the research on the neurology of stuttering that does have
therapy potential has been largely driven by a speech-motor model that is
designed to account for the efficacy of fluency-inducing strategies and
strategies that have been shown to yield therapy benefits. Investigations on
methods that will induce neuroplasticity are overdue. Strategies profitable with
other disorders have only occasionally been employed. However, there are signs
that investigations on the neurology of adults who have recovered from stuttering
are slowly being recognized for their potential in this regard.
PMID- 28413061
TI - Mechanical behavior of bulk direct composite versus block composite and lithium
disilicate indirect Class II restorations by CAD-FEM modeling.
AB - OBJECTIVES: To study the influence of resin based and lithium disilicate
materials on the stress and strain distributions in adhesive class II mesio
occlusal-distal (MOD) restorations using numerical finite element analysis (FEA).
To investigate the materials combinations in the restored teeth during
mastication and their ability to relieve stresses. METHODS: One 3D model of a
sound lower molar and three 3D class II MOD cavity models with 95 degrees cavity
margin-angle shapes were modelled. Different material combinations were
simulated: model A, with a 10MUm thick resin bonding layer and a resin composite
bulk filling material; model B, with a 70MUm resin cement with an indirect CAD
CAM resin composite inlay; model C, with a 70MUm thick resin cement with an
indirect lithium disilicate machinable inlay. To simulate polymerization
shrinkage effects in the adhesive layers and bulk fill composite, the thermal
expansion approach was used. Shell elements were employed for representing the
adhesive layers. 3D solid CTETRA elements with four grid points were employed for
modelling the food bolus and tooth. Slide-type contact elements were used between
the tooth surface and food. A vertical occlusal load of 600 N was applied, and
nodal displacements on the bottom cutting surfaces were constrained in all
directions. All the materials were assumed to be isotropic and elastic and a
static linear analysis was performed. RESULTS: Displacements were different in
models A, B and C. Polymerization shrinkage hardly affected model A and
mastication only partially affected mechanical behavior. Shrinkage stress peaks
were mainly located marginally along the enamel-restoration interface at occlusal
and mesio-distal sites. However, at the internal dentinal walls, stress
distributions were critical with the highest maximum stresses concentrated in the
proximal boxes. In models B and C, shrinkage stress was only produced by the
70MUm thick resin layer, but the magnitudes depended on the Young's modulus (E)
of the inlay materials. Model B mastication behavior (with E=20GPa) was similar
to the sound tooth stress relief pattern. Model B internally showed differences
from the sound tooth model but reduced maximum stresses than model A and
partially than model C. Model C (with E=70GPa) behaved similarly to model B with
well redistributed stresses at the occlusal margins and the lateral sides with
higher stress concentrations in the proximal boxes. Models B and C showed a more
favorable performance than model A with elastic biomechanics similar to the sound
tooth model. SIGNIFICANCE: Bulk filling resin composite with 1% linear
polymerization shrinkage negatively affected the mechanical behavior of class II
MOD restored teeth. Class II MOD direct resin composite showed greater potential
for damage because of higher internal and marginal stress evolution during resin
polymerization shrinkage. With a large class II MOD cavity an indirect composite
or a lithium disilicate inlay restoration may provide a mechanical response close
to that of a sound tooth.
PMID- 28413062
TI - Assessment of mucosal integrity by quantifying neutrophil granulocyte influx in
murine models of acute intestinal injury.
AB - Intact epithelial body surfaces represent physical barriers which protect the
organism from invading pathogens and loss of nutrients. Barrier malfunction is
closely linked to disorders such as inflammatory bowel disease and graft-versus
host disease. In fact, several pharmacological or radiobiological therapeutic
strategies have side effects that affect epithelial surfaces. In this context,
assays that accurately assess epithelial barrier integrity in patients and animal
models are crucial to create a better understanding of the mechanisms leading to
disease or limiting therapeutic approaches due to barrier disruption. Here, we
tested the ability of the widely used FITC-dextran intestinal permeability
analysis to evaluate loss of intestinal barrier integrity in different murine
models of gut mucosal damage and established influx of neutrophil granulocytes
into the intestinal lamina propria (LP) as an alternative approach. We
demonstrate that the sensitivity and specificity of FITC-dextran intestinal
permeability analysis is relatively low: Although it did represent severe forms
of mucosal damage due to intensive conditioning therapy (high doses of either
total body irradiation (TBI) or chemotherapy) or after conditioning and
allogeneic stem cell transplantation, it did not recognize less severe forms of
damage as after lower doses of TBI or chemotherapy alone. In addition,
discrimination of untreated from irradiated mice by differences in FITC-dextran
translocation was not exact. In contrast, influx of neutrophil granulocytes into
the intestinal LP, which reflects immune activation due to translocation of
microbes and microbial products during intestinal barrier breech, quantitatively
correlated with the severity of intestinal barrier damage. It accurately
represented both severe and less severe forms of intestinal damage as after high
or lower dose TBI or chemotherapy and correctly discriminated treated from
untreated animals. Taken together, we demonstrate the limitations of FITC-dextran
intestinal permeability analysis and identify intestinal neutrophil influx as a
powerful additional tool to measure breakdown of intestinal barrier function.
PMID- 28413063
TI - Amniotic membrane application for the healing of chronic wounds and ulcers.
AB - Wound healing usually follows a predictable sequence and prognosis of events. Its
evolutionary process is the result of a complicated interaction between patient
related factors, the wound, the treatment used and the skills and knowledge of
the professionals who treat them. Only through a meticulous initial assessment of
the wound is it possible to identify the factors that contribute to its
complexity. The challenge for professionals will be to implement efficient
therapies at the right time and in the most cost-efficient way in order to reduce
associated problems, treat the symptoms and expectations of the patients and
achieve adequate wound healing whenever possible. This is particularly evident in
big chronic wounds with considerable tissue loss, which become senescent in the
process of inflammation or proliferation losing the ability to epithelialize.
Generally, chronic wounds do not respond to current treatments, therefore they
need special interventions. AM is a tissue of particular interest as a biological
dressing and it has well-documented reepithelialization effects which are in part
related to its capacity to synthesize and release biological active factors. Our
studies have demonstrated that amniotic membrane (AM) is able to induce
epithelialization in chronic wounds that were unable to epithelialize. AM induces
several signaling pathways that are involved in cell migration and/or
proliferation. Additionally, AM is able to selectively antagonize the anti
proliferative effect of transforming growth factor-beta (TGF-beta) by modifying
the genetic program that TGF-beta induces on keratinocytes. The combined effect
of AM on keratinocytes, promoting cell proliferation/migration and antagonizing
the effect of TGF-beta is the perfect combination, allowing chronic wounds to
move out of their non-healing state and progress into epithelialization.
PMID- 28413064
TI - Systemic sclerosis.
AB - Systemic sclerosis, also called scleroderma, is an immune-mediated rheumatic
disease that is characterised by fibrosis of the skin and internal organs and
vasculopathy. Although systemic sclerosis is uncommon, it has a high morbidity
and mortality. Improved understanding of systemic sclerosis has allowed better
management of the disease, including improved classification and more systematic
assessment and follow-up. Additionally, treatments for specific complications
have emerged and a growing evidence base supports the use of immune suppression
for the treatment of skin and lung fibrosis. Some manifestations of the disease,
such as scleroderma renal crisis, pulmonary arterial hypertension, digital
ulceration, and gastro-oesophageal reflux, are now treatable. However, the burden
of non-lethal complications associated with systemic sclerosis is substantial and
is likely to become more of a challenge. Here, we review the clinical features of
systemic sclerosis and describe the best practice approaches for its management.
Furthermore, we identify future areas for development.
PMID- 28413065
TI - Outcome of low profile mesh plate in management of comminuted displaced fracture
patella.
AB - PURPOSE: To assess the clinical results of using mesh plate in management of
displaced comminuted fracture patella. PATIENTS AND METHODS: Between January 2014
and October 2015, nine patients with closed displaced comminuted fracture patella
were fixed using mesh plate and 2mm mini screws. RESULTS: All fractures united
after an average of 10 weeks. At final follow-up of an average 19.6 months,
average postoperative Lysholm score was 89.1+/-4.9, and average Postoperative
Bostman scale was 27.2+/-3.1. No hardware related complications were recorded.
CONCLUSION: Low profile mesh plate is a good option in management of comminuted
fracture patella with good clinical outcome. This new surgical technique may be
particularly useful in comminuted fractures when patellectomy would otherwise be
considered.
PMID- 28413066
TI - Temporary portal vein embolization is as efficient as permanent portal vein
embolization in mice.
AB - BACKGROUND: Temporary portal vein embolization may be a safe alternative to
permanent portal vein embolization. Such a new approach could be applied in
living-related liver transplantation to increase graft volume before procurement.
The impact of temporary portal vein embolization on occluded liver after
recanalization, however, has never been assessed. Using a mouse model of
temporary portal vein embolization, we investigated (1) the efficiency of
temporary portal vein embolization in inducing nonoccluded liver hypertrophy and
(2) the regeneration potential and functional recovery of embolized liver after
recanalization. METHODS: Selected portal vein branches were occluded using
gelfoam powder (temporary portal vein embolization) or embospheres (permanent
portal vein embolization), n = 5/group. Magnetic resonance volumetry and
angiography were used to determine volumes of the liver lobe and portal vein
branch recanalization. In order to assess the functional and regenerative
capacity of occluded liver lobes, nonoccluded lobes were resected 14 days
(timespan of complete portal vein recanalization) after temporary portal vein
embolization or permanent portal vein embolization. Subsequently, RNA sequencing
was performed to compare the signaling pathways of early liver regeneration among
the groups. RESULTS: Hypertrophy of nonoccluded lobes 30 days after temporary
portal vein embolization and permanent portal vein embolization was similar (103
+/- 26% and 129 +/- 13%, P = .11). Temporary occluded lobes increased their
volumes after nonoccluded lobes resection, reaching similar liver-to-body-weight
ratios and similar functional capacity after 7 days compared with partial
hepatectomy controls (4 +/- 1% vs 4 +/- 1%, P = .22). Partial hepatectomy
activated similar signaling pathways in temporary occluded and native liver.
CONCLUSION: Temporary portal vein embolization induces hypertrophy of
contralateral liver lobes similarly to permanent portal vein embolization in
mice. This experimental work suggests that temporary portal vein embolization may
be considered as a possibility in living liver donation, because regenerative and
functional capacities are preserved in the embolized liver after recanalization
in mice.
PMID- 28413067
TI - Contraception and menstrual bleeding during venous thromboembolism treatment:
Does current practice reflect expert option?
PMID- 28413069
TI - Improving the upper-limb force feasible set evaluation by muscles maximal
isometric force identification and cocontraction factors.
AB - In order to improve the evaluation of the force feasible set (FFS) of the upper
limb which is of great interest in the biomechanics field, this study proposes
two additional techniques. The first one is based on the identification of the
maximal isometric force (MIF) of Hill-based muscles models from sEMG and
isometric force measurements at the hand. The second one considers muscles
cocontraction. The FFS was computed with an upper-limb musculoskeletal model in
three different cases. The first one (M1) considered binary muscular activation
and a simple MIF scaling method based on the weight and muscle length of the
subject. The second one (M2) introduces cocontraction factors determined from
sEMG. The third one (M3) considers the cocontraction factors and the MIF
identification. Finally, M1, M2 and M3 are compared with end-effector force
measurement. M3 outperforms the two other methods on FFS prediction demonstrating
the validity and the usefulness of MIF identification and the consideration of
the cocontraction factors.
PMID- 28413068
TI - Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices.
AB - Adult tissue stem cells (SCs) reside in niches, which, through intercellular
contacts and signaling, influence SC behavior. Once activated, SCs typically give
rise to short-lived transit-amplifying cells (TACs), which then progress to
differentiate into their lineages. Here, using single-cell RNA-seq, we unearth
unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots
of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces,
where progenitors display molecular signatures reflective of spatially distinct
local signals and intercellular interactions. Using lineage tracing, temporal
single-cell analyses, and chromatin landscaping, we show that SC plasticity
becomes restricted in a sequentially and spatially choreographed program,
culminating in seven spatially arranged unilineage progenitors within TACs of
mature follicles. By compartmentalizing SCs into micro-niches, tissues gain
precise control over morphogenesis and regeneration: some progenitors specify
lineages immediately, whereas others retain potency, preserving self-renewing
features established early while progressively restricting lineages as they
experience dynamic changes in microenvironment.
PMID- 28413070
TI - Processing graspable object images and their nouns is impaired in Parkinson's
disease patients.
AB - According to embodiment, the recruitment of the motor system is necessary to
process language material expressing a motor content. Coherently, an impairment
of the motor system should affect the capacity to process language items with a
motor content. The aim of the present study was to assess the capacity to process
graspable objects and their nouns in Parkinson's disease (PD) patients and
healthy controls. Participants saw photos and nouns depicting graspable and non
graspable objects. Scrambled images and pseudo-words served as control stimuli.
At 150 msec after stimulus presentation, they had to respond when the stimulus
referred to a real object, and refrain from responding when it was meaningless
(go-no go paradigm). In the control group, participants gave slower motor
responses for stimuli (both photos and nouns) related to graspable objects as
compared to non-graspable ones. This in keeping with data obtained in a previous
study with young healthy participants. In the PD group, motor responses were
similar for both graspable and non-graspable items. Moreover, error number was
significantly greater than in controls. These findings support the notion that
when the motor circuits are lesioned, like in PD, patients do not show the
typical modulation of motor responses and have troubles in processing graspable
objects and their nouns.
PMID- 28413071
TI - Performance of ultra-low-dose CT for the evaluation of coronary calcification: a
direct comparison with coronary calcium score.
AB - AIM: To evaluate the diagnostic performance of ultra-low-dose computed tomography
(ULDCT) in comparison to standard coronary calcium score (CCS) acquisition for
the evaluation of coronary artery calcification (CAC). MATERIALS AND METHODS:
Standard CCS acquisition and ULDCT were performed in patients referred for
coronary CT angiography for the evaluation of coronary artery disease. CAC in
ULDCT was graded subjectively using a four-point scale (from 0, no calcification,
to 3, severe calcification) for the complete study and for each individual
coronary segment. The summation of all individual coronary segment scores
generated an ULDCT total CAC score. ULDCT results were compared to standard
Agatston score and sensitivity and specificity of ULDCT were calculated. RESULTS:
CCS and ULDCT were performed in 74 patients, with a mean DLP of 77.7 mGy.cm (+/
12.1) and 9.3 mGy.cm (+/-0.6), respectively (p<0.001). Coronary calcification was
detected in 47 patients (63.5%) in standard CCS acquisition (median Agatston
score of 41; interquartile range [IQR]:0263), in comparison to 42 patients
(56.8%) in ULDCT (p<0.001). The sensitivity and specificity of the ULDCT total
CAC score >=1 was 80.9% and 85.2%, respectively, with an accuracy of 82.4%. The
area under the receiver operating characteristic curve for the presence of CAC
was 0.87. CONCLUSION: ULDCT shows good sensitivity, specificity, and overall
accuracy for the detection of coronary calcification with a markedly lower
radiation dose in comparison to CCS. ULDCT is unlikely to miss coronary
calcification in individuals with at least moderate calcium load (Agatston score
>100).
PMID- 28413072
TI - Progressive regression of intracranial arteriovenous malformations after Onyx
embolization.
AB - Progressive regression of cerebral arteriovenous malformations (AVMs) is a rare
phenomenon that may occur spontaneously or after previous surgical or
endovascular incomplete obliteration. We present two cases of AVMs occluded
partially with Onyx followed by the unexpected cure of the lesions with the
angiographic evidences as well as multiannual follow-up.
PMID- 28413073
TI - Effects of short-term weathering on the stable carbon isotope compositions of
crude oils and fuel oils.
AB - A short-term simulated weathering experiment was performed on two crude oils and
two heavy fuel oils under natural conditions to evaluate the effects of natural
weathering processes by using gas chromatography-mass spectrometry combined with
gas chromatography-isotopic ratio mass spectrometry. The results of diagnostic
ratios of n-alkanes show that only odd to even predominance (OEP1, OPE2) and
carbon preference index (CPI) remain stabilized during the 28 d weathering
process, but they cannot effectively distinguish the four types of oils.
Statistical analyses based on paired sample t-test and principal component
analysis (PCA) revealed that stable carbon isotope compositions of n-alkanes in
the four studied oils have no significant changes over the weathering time, and
that the carbon isotope discrimination (Deltadelta13C) of n-alkanes is <30/00. We
have provided evidence that the stable carbon isotope compositions of n-alkanes
compared to n-alkanes diagnostic ratios significantly improve the efficiency and
fidelity of the oil fingerprint identification.
PMID- 28413074
TI - Long-term outcomes of extracorporeal membrane oxygenation support for
postcardiotomy shock.
AB - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a widely used technique
for treating postcardiotomy cardiogenic shock (PCS); however, no study has
compared the long-term outcomes of patients who receive ECMO support for PCS with
those of the general population post cardiac surgery. METHODS: A total of 1141
patients who received ECMO after cardiac surgery between 2000 and 2011 were
identified by using the Taiwan National Health Insurance Research Database. For
each patient, we matched 5 non-ECMO patients who had undergone cardiac surgery by
using propensity scores calculated for age, sex, 12 comorbid diseases, Charlson
score, hospital level, type of cardiac surgery, and year of index
hospitalization. The outcomes included all-cause mortality, readmission for any
cause, and medical expenditure. RESULTS: The incidence of ECMO use after cardiac
surgery in Taiwan was 1.91%. The ECMO group had a significantly higher risk of in
hospital mortality than did the non-ECMO group (61.7% vs 6.8%, odds ratio 22.34,
95% confidence interval 19.06-26.18). The risks of all-cause mortality and first
readmission for any cause were greater in the ECMO group than that in the control
group (P < .001, P < .001) in the first year, whereas no difference was observed
after the first year of follow-up (P = .209, P = .474). Similar results were
observed regarding the medical expenditure of admission after index admission
discharge. CONCLUSIONS: Patients receiving ECMO for PCS had similar outcomes to
those of the non-ECMO group after the first year of follow-up despite
significantly poor outcomes during the in-hospital course.
PMID- 28413075
TI - Abrasion and blunt tissue trauma study of a novel flexible robotic system in the
porcine model.
AB - OBJECTIVES: The objective of this study was to determine if a flexible robotic
system caused increased tissue reaction when accessing the oropharynx and
hypopharynx compared to intubation controls in only 2 scenarios: high speed
tissue impact and multiple unit insertions and retractions. The data obtained
were submitted as part of the entirety of information submitted for FDA approval.
METHODS: This study consisted of 5 groups of Yorkshire pigs (2 animals per
group). On Day 0, all animals were intubated. For group 1 (control), a second
endotracheal tube was advanced to just above the vocal cords. In abrasion groups
2 and 3, the flexible robotic system was advanced against the oropharyngeal and
hypopharyngeal tissues, respectively. In blunt trauma groups 4 and 5, the
flexible robotic system was advanced at maximum speed (22mm/s) to collide with
oropharyngeal and hypopharyngeal tissues, respectively. Pre- and post-procedure
endoscopic assessments of tissue reaction were performed daily for 4 days. An
independent reviewer graded tissue reaction using a 0-3 point scale. RESULTS:
Tissue reaction scores at each observation time point for all test groups were
less than or equal to control scores except for one instance of moderate scoring
(2 out of 3) on Day 2 for an animal in the blunt trauma group where reaction was
likely intubation-related rather than device impact related. Otherwise, all
flexible robotic system-treated animal scores were less than 1 by Day 4.
CONCLUSIONS: In this limited study, the flexrobotic system afforded surgical
access to the oropharynx and hypopharynx without an increased level of abrasion
or tissue trauma when compared to intubation alone.
PMID- 28413076
TI - Detection of endolymphatic hydrops using traditional MR imaging sequences.
AB - PURPOSE: The purpose of this study was to determine whether Meniere's disease
(MD) produces endolymphatic cavity size changes that are detectable using
unenhanced high-resolution T2-weighted MRI. MATERIALS & METHODS: This
retrospective case-control study included patients with documented MD who had a
high-resolution T2-weighted or steady-state free procession MRI of the temporal
bones within one month of diagnosis, between 2002 and 2015. Patients were
compared to age- and sex- matched controls. Cross sectional area, length, and
width of the vestibule and utricle were measured in both ears along with the
width of the basal turn of the cochlea and its endolymphatic space. Absolute
measurements and ratios of endolymph to perilymph were compared between affected,
contralateral, and control ears using analysis of variance and post-hoc pairwise
comparisons. RESULTS: Eighty-five case-control pairs were enrolled. Mean utricle
areas for affected, contralateral, and control ears were 0.038cm2, 0.037cm2, and
0.033cm2. Mean area ratios for affected, contralateral, and control ears were
0.32, 0.32, and 0.29. There was a statistically significant difference between
groups for these two variables; post-hoc comparisons revealed no difference
between affected and contralateral ears in Meniere's patients, while ears in
control patients were different from the ears of patients with MD. All other
measurements failed to show significant differences. CONCLUSIONS: Enlargement of
the endolymphatic cavity can be detected using non-contrast T2-weighted MRI. MRI,
using existing protocols, can be a useful diagnostic tool for the evaluation of
MD, and intratympanic or delayed intravenous contrast may be unnecessary for this
diagnosis.
PMID- 28413077
TI - Trichomonosis outbreak in a flock of canaries (Serinus canaria f. domestica)
caused by a finch epidemic strain of Trichomonas gallinae.
AB - In the present paper, an outbreak of trichomonosis in a flock of 15 breeding
pairs of canaries is described. Trichomonosis was diagnosed on characteristic
clinical signs, microscopic examination of crop/esophageal swabs, gross pathology
and histopathology. Trichomonads were successfully grown in culture media and
were characterized by multi-locus sequence typing. The three genomic loci ITS1
5.8S-ITS2, 18S rRNA and Fe-hydrogenase were analyzed. Molecular characterization
confirmed the finch trichomonosis strain, identical to the strain that caused
emerging disease in free-living passerine birds in Europe. Flock treatment with
metronidazole (200mg/L) in drinking water for 5days was partially effective.
After individual treatment with oral application of metronidazole (20mg/kg SID)
for 5days no further clinical signs were observed in the flock over next 30
months.
PMID- 28413078
TI - Evaluation of immunochromatographic test (ICT) strips for the serological
detection of Babesia bovis and Babesia bigemina infection in cattle from Western
Java, Indonesia.
AB - Three types of immunochromatographic test (ICT) strips were prepared for the
detection of an antibody response against spherical body protein 4 (SBP-4) of
Babesia bovis (bovICT), C-terminal-truncated rhoptry-associated protein 1
(rRAP1/CT17) of B. bigemina (bigICT), and the combination of both proteins (dual
ICT). The evaluation of their performance was conducted using a confirmed
positive and negative serum panel for B. bovis and B. bigemina. Together with
ELISA, the ICT strips were applied to determine the seroprevalence of bovine
babesiosis in Western Java, Indonesia. Among 991 serum samples, 28.4%, 25.3%, and
24.5% of cattle were detected to be seropositive to B. bovis infection using
ELISA, bovICT, and dual-ICT, respectively. B. bigemina seropositive was detected
in 27.1%, 24.2%, and 22.8% of samples using ELISA, bigICT, and dual-ICT,
respectively. The comparison of ICT strips and ELISA results using field serum
samples showed good agreement with Kappa values >0.7 between all methods The
application of ICT strips is preferable in the field situations where rapid
diagnosis is required. Furthermore, the data showed the current seroprevalence of
bovine babesiosis in Western Java, Indonesia, and efficient control strategies
are needed to reduce economic losses due to the disease.
PMID- 28413079
TI - Mexican consensus on dyspepsia.
AB - Since the publication of the 2007 dyspepsia guidelines of the Asociacion Mexicana
de Gastroenterologia, there have been significant advances in the knowledge of
this disease. A systematic search of the literature in PubMed (01/2007 to
06/2016) was carried out to review and update the 2007 guidelines and to provide
new evidence-based recommendations. All high-quality articles in Spanish and
English were included. Statements were formulated and voted upon using the Delphi
method. The level of evidence and strength of recommendation of each statement
were established according to the GRADE system. Thirty-one statements were
formulated, voted upon, and graded. New definition, classification, epidemiology,
and pathophysiology data were provided and include the following information:
Endoscopy should be carried out in cases of uninvestigated dyspepsia when there
are alarm symptoms or no response to treatment. Gastric and duodenal biopsies can
confirm Helicobacter pylori infection and rule out celiac disease, respectively.
Establishing a strong doctor-patient relationship, as well as dietary and
lifestyle changes, are useful initial measures. H2-blockers, proton-pump
inhibitors, prokinetics, and antidepressants are effective pharmacologic
therapies. H.pylori eradication may be effective in a subgroup of patients. There
is no evidence that complementary and alternative therapies are beneficial, with
the exception of Iberogast and rikkunshito, nor is there evidence on the
usefulness of prebiotics, probiotics, or psychologic therapies. The new consensus
statements on dyspepsia provide guidelines based on up-to-date evidence. A
discussion, level of evidence, and strength of recommendation are presented for
each statement.
PMID- 28413080
TI - Effect of oral exposure to artificially weathered Deepwater Horizon crude oil on
blood chemistries, hepatic antioxidant enzyme activities, organ weights and
histopathology in western sandpipers (Calidris mauri).
AB - Shorebirds were among birds exposed to Mississippi Canyon 252 (MC252) crude oil
during the 2010 Deep Water Horizon (DWH) oil spill in the Gulf of Mexico. The
western sandpiper (Calidris mauri) was chosen as one of four species for initial
oral dosing studies conducted under Phase 2 of the avian toxicity studies for the
DWH Natural Resource Damage Assessment (NRDA). Thirty western sandpipers were
assigned to one of three treatment groups, 10 birds per group. The control group
was sham gavaged and the treatment groups were gavaged with 1 or 5mL oil kg bw-1
daily for 20 days. Periodic blood samples for hemoglobin measurements were
collected during the trial. A final blood sample used to determine hemoglobin
concentration in addition to complete blood counts, plasma clinical chemistries,
haptoglobin concentration and plasma electrophoresis was collected when birds
were euthanized and necropsied on day 21. Tissues were removed, weighed and
processed for subsequent histopathological evaluation. There were numerical
decreases in hemoglobin concentrations in oil-dosed birds over the 21-day trial,
but values were not significantly different compared to controls on day 21. There
were no significant differences between controls and oiled birds in complete
blood counts, plasma chemistries, haptoglobin concentration, and plasma
electrophoresis endpoints. Of the hepatic oxidative stress endpoints assessed,
the total antioxidant capacity assessment (Trolox equivalents) for the control
group was lower compared to the 1mL oil kg bw-1 group. Absolute liver weights in
the 5mL oil kg bw-1 group were significantly greater compared to controls. While
not conclusive, the numerical decrease in hemoglobin concentration and
significant increase in absolute liver weight are consistent with exposure to
oil. Histological changes in the adrenal gland could be considered a non-specific
indicator of stress resulting from exposure to oil. It is possible that the
quantity of oil absorbed was not sufficient to induce clearly evident hemolytic
anemia or that the western sandpiper is relatively insensitive to ingested oil.
PMID- 28413081
TI - How can Video-Based Sessions Improve E-Learning of Respiratory Physiology?
PMID- 28413082
TI - Primary Sjogren Syndrome With Pleural Effusion.
PMID- 28413083
TI - A novel nuclear xenobiotic receptors (AhR/PXR/CAR)-mediated mechanism of DEHP
induced cerebellar toxicity in quails (Coturnix japonica) via disrupting CYP
enzyme system homeostasis.
AB - Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife
animal and human through environment and food chain, including the effect of
brain development and impacted neurobehavioral outcomes. However, DEHP exposure
caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted
potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500
and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral
abnormality and cerebellar histopathological alternation were observed in DEHP
induced quails. DEHP exposure increased the contents of total Cytochrome P450s
(CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c
reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The
expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP
enzyme isoforms were also influenced in cerebellum by DEHP exposure. These
results suggested that DEHP exposure caused the toxic effects of quail
cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis
via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom
and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird.
Finally, this study provided new evidence that DEHP-induced toxic effect of quail
cerebellum was associated with activating the NXRs responses and disrupting the
CYP enzyme system homeostasis.
PMID- 28413085
TI - Letter to Editor: A Case of Election-Induced Shingles?
PMID- 28413084
TI - Brominated dioxins/furans and hydroxylated polybrominated diphenyl ethers:
Occurrences in commercial 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) and 2,4,6
tribromophenol, and formation during synthesis of BTBPE.
AB - Polybrominated dibenzo-p-dioxins (PBDDs) and hydroxylated polybrominated diphenyl
ethers (OH-PBDEs) can be formed from bromophenols (BPs) by thermal degradation,
biosynthesis or phototransformation. However, it is unknown whether PBDDs and OH
PBDEs can be formed during the chemical production processes that utilize BPs as
raw materials. 2,4,6-tribromophenol (2,4,6-TBP) is an important raw material for
the synthesis of 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), a novel brominated
flame retardant. In this study, PBDDs, polybrominated dibenzofurans (PBDFs) and
OH-PBDEs have been identified and quantified in commercially available BTBPE and
2,4,6-TBP. Furthermore, their formation as unintentional by-products during the
laboratory synthesis of BTBPE from 2,4,6-TBP and 1,2-dibromoethane in the
presence of sodium carbonate has also been investigated. 2,3,7,8-substituted
PBDDs and PBDFs (2,3,7,8-PBDD/Fs) were undetectable in commercial samples of
BTBPE and present in low levels (nanogram per gram) in 2,4,6-TBP. Two
tetrabrominated dibenzo-p-dioxins (TeBDDs), namely 1,3,6,8- and 1,3,7,9-TeBDD,
and three hydroxylated pentabrominated diphenyl ethers (OH-pentaBDEs), namely 4'
OH-BDE121, 2'-OH-BDE121, and 6'-OH-BDE100, were identified or tentatively
identified, and quantitatively estimated to be at concentrations in the range of
undetectable to several thousands of nanograms per gram in commercial BTBPE and
2,4,6-TBP. TeBDDs and OH-pentaBDEs were formed as by-products from 2,4,6-TBP
during BTBPE synthesis. Further studies need to be conducted in order to
determine whether PBDD/Fs and OH-PBDEs are also formed during the industrial
synthesis of other chemical compounds that utilize BPs as raw materials or
intermediates.
PMID- 28413086
TI - Clinically Feasible Stratification of 3-Year Chronic Disease Risk in Primary
Care: The Mental Health Integration Risk Score.
AB - BACKGROUND: Depression is a common illness that imposes a disproportionately
large health burden. Depression is generally associated with a higher prevalence
of chronic disease risk factors and may contribute to higher chronic disease
risk. OBJECTIVE: This study aimed to create and validate sex-specific Mental
Health Integration Risk Scores (MHIRS) that predict 3-year chronic disease
diagnosis. METHODS: MHIRS was created to predict the first diagnosis of any of
the 10 chronic diseases in patients completing a Patient Health Questionnaire-9
Depression Survey who were free at baseline from those 10 chronic disease
diagnoses. MHIRS used sex-specific weightings of Patient Health Questionnaire 9
results, age, and components of the complete metabolic profile and complete blood
count in randomly chosen derivation (70%) and validation (30%) groups. RESULTS:
Among females (N = 10,162, age: 48 +/- 16), c-statistics for the composite
chronic disease end point were 0.746 (0.725, 0.767) for the derivation group and
0.717 (0.682, 0.753) for the validation group, whereas males (N = 4615, age: 48
+/- 15) had 0.755 (0.727, 0.783) and 0.742 (0.702, 0.782). In the validation
group, MHIRS strata of low-, moderate-, and high-risk categories had hazard
ratios (HR) for any 3-year chronic disease diagnosis among females of HR = 3.42
for moderate vs low and HR = 9.75 for high vs low, whereas males had HR = 4.80
and HR = 10.68, respectively (all p < 0.0001). CONCLUSION: A clinical decision
tool comprised by depression severity and common laboratory tests, and MHIRS
provides very good stratification of a 3-year chronic disease diagnosis. Designed
to be calculated electronically by an electronic health record, MHIRS can be
efficiently obtained by clinicians to identify patients at higher chronic disease
risk who require further evaluation and more precise clinical management.
PMID- 28413087
TI - Does Social Support Moderate the Association Among Major Depression, Generalized
Anxiety Disorder, and Functional Disability in Adults With Diabetes?
AB - BACKGROUND: Diabetes requires complex self-management routines to prevent the
development of functional disability. Relative to people without diabetes, those
with diabetes are more likely to have comorbid major depressive disorder (MDD)
and generalized anxiety disorder (GAD), which also increase the likelihood of
functional disability. Social support is associated with positive health outcomes
in people with comorbid diabetes and mental disorders and may serve as a buffer
against functional disability, though this possibility has yet to be examined.
OBJECTIVES: This study examined whether social support moderates the association
between MDD or GAD and functional disability in adults with diabetes. Adults with
MDD or GAD were expected to report greater disability than those without MDD or
GAD. This association was expected to be stronger in people reporting lower
social support relative to those reporting higher social support. METHODS: Data
came from the cross-sectional 2012 Canadian Community Health Survey-Mental Health
(n = 1764). Diabetes status, social support, and functional disability were
assessed via self-report; past-year MDD and GAD were assessed with structured
diagnostic interviews. RESULTS: Linear regression analyses, conducted separately
for MDD and GAD, indicated main effects of past-year MDD and GAD, such that those
with a mental disorder reported greater functional disability than those without
a mental disorder. Social support did not moderate the associations between
either MDD and functional disability or GAD and functional disability.
CONCLUSIONS: In this nationally representative population study, both MDD and GAD
predicted greater functional disability in adults with diabetes. Social support,
however, did not moderate these associations.
PMID- 28413088
TI - A Retrospective Analysis of Neurocognitive Impairment in Older Patients With Burn
Injuries.
AB - BACKGROUND: Older adults comprise a growing proportion of the United States
population that is at risk for burns. However, few studies have examined
cognitive function in this patient population. OBJECTIVE: The purpose of this
study was to measure the prevalence and incidence of dementia and delirium in
older adults admitted for burn injuries. METHODS: This was an Institutional
Review Board-approved, retrospective study of all patients 65 years and older
admitted to the University of North Carolina Jaycee Burn Center from 2005-2015.
Data extracted from the medical records included patient demographics,
characteristics of the burn injury, incidence of delirium, incidence of
psychiatric consultation, diagnosis of dementia, disposition, and mortality. The
primary outcomes of interest were the prevalence and incidence of dementia and
delirium. Secondary outcomes included length of stay and cost of hospitalization.
RESULTS: A total of 392 patients were included. These patients had a median age
of 74 years and a median total body surface area burn of 7%. On admission, 44
patients (11%) had a diagnosis of dementia. An additional 28 patients were
diagnosed with dementia during hospitalization for a total of 72 patients (18%);
154 patients (39%) were diagnosed with delirium. After controlling for burn
severity, dementia and delirium were significantly associated with length of
stay, incidence of psychiatry consultation, and discharge to a skilled nursing
facility. CONCLUSIONS: Physicians should have high suspicion for dementia and
delirium in older patients admitted for burn injuries. Dementia and delirium are
associated with morbidity in older patients with burn injuries.
PMID- 28413089
TI - Loperamide Abuse and Life-Threatening Arrhythmias: A Case Report and Literature
Review.
PMID- 28413090
TI - Serum Valproic Acid Levels During Initial Conversion of Antituberculoid Therapy
in Bipolar Mania: A Case Report and Literature Review.
PMID- 28413092
TI - Resisting the Urge to Act: DREADDS Modifying Habits: (Trends in Neurosciences 40,
61-62; 2017).
PMID- 28413091
TI - "What We Have Here is a Failure to Communicate": Association of Preferred
Language With the Rate of Psychiatric Consultation.
AB - BACKGROUND: In the United States, people with limited English proficiency (LEP)
receive poorer medical care than those proficient in English. Few studies
demonstrate how linguistic barriers complicate psychiatric care; in consultation
liaison (C-L) psychiatry, there are no published data about care disparities for
patients with LEP or for whom English is not the preferred language (PL).
OBJECTIVE: We sought to determine if PL affects the psychiatric consultation
rate. METHODS: Among adult patients admitted during 1 year to a large urban
academic medical center, we compared psychiatric consultation rates in English PL
patients with non-English PL patients. PL was ascertained from demographics
during the medical record. The occurrence of psychiatric consultation was
ascertained from C-L service logs. RESULTS: There were 54,534 admissions: the no
consultation group (N = 53,196) and the consultation group (N = 1,398). English
as PL was more common in the consult group (72.0% of consult group, 62.0% of no
consult group, chi2 = 92.98, p < 0.0001). Spanish speakers were underrepresented
in the consult group (14.2% of consult, 25.8% of no-consult, chi2 = 98.78, p <
0.0001). CONCLUSION: Primary teams requested more consultations for patients
whose PL was English than for patients with other PLs, suggesting that
psychiatric needs of patients with non-English PL may be unaddressed. This is the
first study to demonstrate a disproportionately low rate of general hospital
psychiatric consultations in this population. Further study is necessary to
confirm and understand this disparity. We recommend routine use of professional
interpreters and low threshold for consultation in patients with non-English PL.
PMID- 28413093
TI - [Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between
2008 and 2015].
AB - INTRODUCTION: Some studies suggest that thrombotic thrombocytopenic purpura (TTP)
occurs more often in African Americans. However there is low evidence for this in
the literature. The aim of our study was to describe the clinical and biological
characteristics of TTP in the Afro-Caribbean population of Martinique. METHODS:
We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France
hospital between 2008, January 1st and 2015, December 31st. Diagnosis was
confirmed if ADAMTS-13 activity was<10 %. RESULTS: Ten patients were included,
corresponding to an average annual incidence of 3.2 cases/year/million
individuals. None of the patient presented with the association of the five
characteristic features of TTP. Microangiopathic haemolytic anaemia and severe
peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to
diagnosis. There was no kidney involvement in 90 % of all patients, but severe
neurological manifestations occurred in 70 %. Classical management including
corticosteroids and plasma exchanges allowed clinical remission in 6 out of the
10 cases. If necessary, rituximab or cyclophosphamide was used. The overall
survival rate was 90 %. CONCLUSION: In Martinique, the incidence of TTP is twice
that reported in similar studies in France. Clinical manifestations seem to
differ by more common and more severe neurological involvement. Mortality is low,
in part, due to optimal care.
PMID- 28413094
TI - [Pachymeningitis].
AB - Pachymeningitis is a fibrosing and inflammatory process, which involves the dura
mater. Some pachymeningitis are cranial and induce headaches and cranial nerve
palsies. Others are spinal and responsible for nerve roots or spinal cord
compression. MRI shows contrast enhancement thickening of the dura mater.
Etiologies are infectious (syphilis, tuberculosis, etc.) or inflammatory
(sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease,
idiopathic). Corticosteroids are the main treatment. The use of immunosuppressive
drugs or rituximab is yet to be determined and probably adapted to each etiology.
PMID- 28413095
TI - [The reform of the third cycle of medical studies: What changes for internal
medicine?]
PMID- 28413096
TI - Implementing WebGL and HTML5 in Macromolecular Visualization and Modern Computer
Aided Drug Design.
AB - Web browsers have long been recognized as potential platforms for remote
macromolecule visualization. However, the difficulty in transferring large-scale
data to clients and the lack of native support for hardware-accelerated
applications in the local browser undermine the feasibility of such utilities.
With the introduction of WebGL and HTML5 technologies in recent years, it is now
possible to exploit the power of a graphics-processing unit (GPU) from a browser
without any third-party plugin. Many new tools have been developed for biological
molecule visualization and modern drug discovery. In contrast to traditional
offline tools, real-time computing, interactive data analysis, and cross-platform
analyses feature WebGL- and HTML5-based tools, facilitating biological research
in a more efficient and user-friendly way.
PMID- 28413097
TI - mGlu2/3 Receptor Antagonists as Novel Antidepressants.
AB - Based on the discovery of the robust antidepressant effects of ketamine in
patients with depression, including those with treatment-resistant depression,
agents acting on the glutamatergic system have drawn much attention as potential
novel antidepressants. Among the agents acting on the glutamatergic system,
preclinical data have indicated that the group II metabotropic glutamate (mGlu)
receptors, mGlu2 and mGlu3, are attractive targets for the development of novel
antidepressants. The antidepressant effects of mGlu2/3 receptor antagonists have
been demonstrated in rodent models, and the synaptic and neural mechanisms
underlying the antidepressant effects of these compounds have been investigated.
Furthermore, these findings have indicated the similarities of the antidepressant
effects and of the mechanisms underlying these effects between mGlu2/3 receptor
antagonists and ketamine. Based on the results obtained hitherto, here I discuss
the potential for mGlu2/3 receptor antagonists to be developed as next-generation
antidepressants.
PMID- 28413098
TI - Therapeutic Inhibition of Complement: Well Worth the Risk.
AB - Complement is an integral part of the immune system and protects against
infection. Complement-mediated immunopathology in many autoimmune diseases and
syndromes has led to the therapeutic targeting of complement and to questions
around the safety of complement inhibition. Here; I examine and clarify the risks
associated with complement therapeutics.
PMID- 28413099
TI - Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic
arthritis, and ankylosing spondylitis.
AB - OBJECTIVE: The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed
the most consistent literature to indicate the best strategy for the second-line
biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis
(SpA), and psoriatic arthritis (PsA). METHODS: Systematic review of the
literature to identify English-language articles on efficacy of second-line
biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted
from available randomized, controlled trials, national biologic registries,
national healthcare databases, post-marketing surveys, and open-label
observational studies. RESULTS: Some previously stated variables, including the
patients' preference, the indication for anti-tumor necrosis factor (TNF)
monotherapy in potential childbearing women, and the intravenous route with dose
titration in obese subjects resulted valid for all the three rheumatic
conditions. In RA, golimumab as second-line biologic has the highest level of
evidence in anti-TNF failure. The switching strategy is preferable for responder
patients who experience an adverse event, whereas serious or class-specific side
effects should be managed by the choice of a differently targeted drug. Secondary
inadequate response to etanercept (ETN) should be treated with a biologic agent
other than anti-TNF. After two or more anti-TNF failures, the swapping to a
different mode of action is recommended. Among non-anti-TNF targeted biologics,
to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of
efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing
the first anti-TNF, the switch strategy to a second is advisable, taking in
account the evidence of adalimumab efficacy in patients with uveitis. The
severity of psoriasis, of articular involvement, and the predominance of
enthesitis and/or dactylitis may drive the choice toward ustekinumab or
secukinumab in PsA, and the latter in AS. CONCLUSION: Taking in account the
paucity of controlled trials, second-line biologic therapy may be reasonably
optimized in patients with RA, SpA, and PsA.
PMID- 28413100
TI - Colchicine resistance and intolerance in familial mediterranean fever:
Definition, causes, and alternative treatments.
AB - BACKGROUND: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory
syndrome characterized by recurrent serositis or arthritis attacks and, in some
patients, chronic subclinical inflammation that predisposes to secondary
amyloidosis. Colchicine is the gold standard of treatment, which reduces attack
frequency and amyloidosis risk. However, up to 5% of patients are considered
resistant or inadequately respond to colchicine, and some others cannot tolerate
the side effects of effective doses of colchicine (colchicine intolerant).
METHODS: We examine how the definition of colchicine resistance has evolved along
with various characteristics of colchicine that may help explain unresponsiveness
to the drug. RESULTS: Key factors in assessing colchicine resistance include
attack frequency and severity, levels of acute phase reactants, colchicine dosage
and composition, and treatment compliance. Promising clinical results have been
obtained with biologics targeting interleukin-1 in colchicine-resistant or
intolerant patients with FMF. CONCLUSIONS: These results underscore the need to
identify patients who are not optimally managed with colchicine and who might
therefore benefit from additional biologic therapies.
PMID- 28413101
TI - Evidence for choosing biologic disease-modifying anti-rheumatic drugs in the
treatment of Behcet disease.
PMID- 28413102
TI - [Antibiotic susceptibility of Staphylococcus aureus and Streptococcus pneumoniae
in healthy carrier individuals in primary care in Barcelona area].
AB - INTRODUCTION: The information available on antibiotic resistance patterns are
generally based on specimens from hospitalised individuals. This study was aimed
at evaluating the antibiotic resistance rate of nasal carriage strains of
Staphylococcus aureus and Streptococcus pneumoniae in healthy individuals, in
accordance with age and gender, attended in Primary Care Centres (PCC). DESIGN:
Cross-sectional study. SETTING: Seven PCC in the Barcelona area. PARTICIPANTS:
Healthy nasal carriers aged 4years or more who did not present with any sign of
infectious disease, and had not taken any antibiotic or had been hospitalised in
the previous 3months. MAIN MEASUREMENTS: A total of 3,969 nasal swabs valid for
identification were collected between 2010 and 2011 and were sent to one central
microbiological laboratory for isolation of both pathogens. Resistance to common
antibiotics was determined on the basis of the current European Committee on
Antimicrobial Susceptibility Testing guidelines on cut-off points. RESULTS: The
prevalence of methicillin-resistant S.aureus was 1.3% (95%CI: 0.5-2.1%), with
resistance rates of 87.1% to phenoxymethylpenicillin and 11.6% to azithromycin,
with no significant differences with age and gender. A total of 2.4% (95CI%: 0.1
4.7%) of the pneumococcal strains were highly resistant to both
phenoxymethylpenicillin and macrolides, whereas the highest resistance rates were
to cefaclor (53.3%), followed by tetracycline (20%) and cefuroxime (12.1%).
CONCLUSIONS: These pathogens have lower resistance rates in the community than in
the hospital setting. Primary Care physicians must be more aware of the current
antimicrobial resistance, in order to ensure prudent use of antibiotics.
PMID- 28413103
TI - Do larval types affect genetic connectivity at sea? Testing hypothesis in two
sibling marine gastropods with contrasting larval development.
AB - In marine environments, connectivity among populations of benthic invertebrates
is provided primarily by dispersion of larvae, with the duration of pelagic
larval phase (PLD) supposed to represent one of the major factor affecting
connectivity. In marine gastropods, PLD is linked to specific larval development
types, which may be entirely intracapsular (thus lacking a pelagic dispersal), or
include a short pelagic lecithotrophic or a long planktotrophic phase. In the
present study, we investigated two sibling species of the cosmopolitan
neogastropod genus Columbella (commonly known as dove shells): Columbella
adansoni Menke, 1853, from the Macaronesian Atlantic archipelagos, with
planktotrophic development, and Columbella rustica Linnaeus, 1758, from the
Mediterranean Sea, with intracapsular development. We expected to find
differences between these two sister species, in terms of phylogeographic
structure, levels of genetic diversification and spatial distribution of genetic
diversity, if PLD was actually a relevant factor affecting connectivity. By
analysing the sequence variation at the cytochrome c oxidase subunit I (COI) in
167 specimens of the two species, collected over a comparable geographic range,
we found that Columbella adansoni, the species with planktotrophic development,
and thus longer PLD, showed no phylogeographic structure, lower levels of genetic
diversity, interpopulational variance lower than the intrapopulational one and no
spatial structure in the distribution of the genetic diversity; Columbella
rustica, the species with intracapsular development, thus with evidently lower
dispersal abilities, showed a clear phylogeographic structure, higher levels of
genetic diversity, high interpopulational and low intrapopulational variance, and
a clear signature of global spatial structure in the distribution of the genetic
diversity. Thus, in this study, two sibling species differing almost only in
their larval ecology (and PLD), when compared for their genetic variation showed
patterns supporting the hypothesis that PLD is a major factor affecting genetic
connectivity. Therefore, it seems reasonable to expect that the ecological
attributes of the marine communities - also in terms of the variation in larval
ecology of the species involved - are taken into the due consideration in
conservation actions, like the design of marine protected areas networks.
PMID- 28413104
TI - Altered epiphyte community and sea urchin diet in Posidonia oceanica meadows in
the vicinity of volcanic CO2 vents.
AB - Ocean acidification (OA) predicted for 2100 is expected to shift seagrass
epiphyte communities towards the dominance of more tolerant non-calcifying taxa.
However, little is known about the indirect effects of such changes on food
provision to key seagrass consumers. We found that epiphyte communities of the
seagrass Posidonia oceanica in two naturally acidified sites (i.e. north and
south sides of a volcanic CO2 vent) and in a control site away from the vent at
the Ischia Island (NW Mediterranean Sea) significantly differed in composition
and abundance. Such differences involved a higher abundance of non-calcareous
crustose brown algae and a decline of calcifying polychaetes in both acidified
sites. A lower epiphytic abundance of crustose coralline algae occurred only in
the south side of the vents, thus suggesting that OA may alter epiphyte
assemblages in different ways due to interaction with local factors such as
differential fish herbivory or hydrodynamics. The OA effects on food items
(seagrass, epiphytes, and algae) indirectly propagated into food provision to the
sea urchin Paracentrotus lividus, as reflected by a reduced P. oceanica
exploitation (i.e. less seagrass and calcareous epiphytes in the diet) in favour
of non-calcareous green algae in both vent sites. In contrast, we detected no
difference close and outside the vents neither in the composition of sea urchin
diet nor in the total abundance of calcareous versus non-calcareous taxa. More
research, under realistic scenarios of predicted pH reduction (i.e. <= 0.32 units
of pH by 2100), is still necessary to better understand cascading effects of this
altered urchin exploitation of food resources under acidified conditions on
ecosystem diversity and function.
PMID- 28413105
TI - Investigation of OMNIgene.SPUTUM performance in delayed tuberculosis testing by
smear, culture, and Xpert MTB/RIF assays in Uganda.
AB - OMNIgene.SPUTUM (OM-S) is a sample transport reagent designed to work with all
tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated
sputum samples were assayed in several tests after multiday holds. Raw sputa from
100 patients underwent direct smear microscopy, were manually split and assigned
to the OM-S group [OM-S added at collection (no other processing required) and
tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC)
group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of
collection). Concentrated smear microscopy, Lowenstein Jensen (LJ) culture, and
mycobacteria growth indicator tube (MGIT) culture were performed. For patients
with negative direct smear, a second sample was split, with SOC (raw sputum) and
OM-S portions (sediment) tested in the Xpert MTB/RIF (Xpert) assay. OM-S group
and SOC group results were strongly concordant on all four tests [range, 89%
(MGIT)-97% (Xpert)]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement
with SOC MGIT as reference. OM-S specimens had lower culture contamination rates
(3% vs. 10% LJ; 2% vs. 5% MGIT) but required, on average, 5.6 additional days to
become MGIT-positive. The findings suggest that samples held/transported in OM-S
are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform
comparably to fresh sputum samples. Larger feasibility studies are warranted.
PMID- 28413106
TI - Heterotopic Ossification in adults following a burn: A phenomenological analysis.
AB - Heterotopic Ossification (HO) is a rare but severely debilitating complication
after a burn. Despite there being literature of varying quality explaining the
postulated pathological process, risk factors and treatment for HO, the
individual experiences of adults diagnosed with HO following a burn, remains
unreported. This study sought to explore and describe burn survivors' experiences
of HO to gain a greater understanding of the clinical needs for this unique
patient population. A phenomenological inquiry of five men and one woman selected
through purposeful sampling collected in-depth interviews analysed using
Colaizzi's method of data analysis. Five emergent themes: (1) Early signs and
symptoms, (2) Impact on the rehabilitation journey, (3) The role of the health
care professionals (4) Loss of independence and an increased reliance on others
and, (5) Learning to live with it: uncertainty, hope and adaptation. Eleven
cluster themes were identified, highlighting the meaning of each emergent theme.
These findings describe the significant impact the unique symptomology of HO had
on the physical and psychosocial functioning of participants throughout the
rehabilitation journey. Central to engagement in rehabilitation, is the
participants' desire for autonomy particularly in the domains of living
independently and community re-integration.
PMID- 28413107
TI - Upregulation of MAOA in the hippocampus results in delayed depressive-like
behaviors in burn mice.
AB - OBJECTIVE: To observe depressive-like behavior and hippocampus monoamine oxidase
A (MAOA) changes in burned mice. METHODS: We tested depression and anxiety like
behaviors of burn C57 mice with the sucrose preference test, forced swimming test
(FST), open field test and elevated plus maze test and then detected the MAOA
content and MAOA gene transcriptional levels in the hippocampus with western blot
analysis and real-time quantitative PCR analysis. We then sought to reverse
depressive-like behavior of burned mice with an MAOA inhibitor. RESULTS: (1) Mice
showed depressive and anxiety like behaviors one week after they were burned; (2)
The content of MAOA in the hippocampus of burned mice was significantly higher
than that in control mice (P<0.05); (3) MAOA gene transcription in the
hippocampus of burned mice was significantly increased (MAOA mRNA was increased,
P<0.05); (4) treatment with a MAOA inhibitor (phenelzine) significantly increased
the sucrose preference rate and decreased FST immobility time in burned mice, and
also decreased elevated expression of MAOA in the hippocampus of burned mice.
CONCLUSION: Burned mice showed "delayed" depressive-like behavior combined with a
degree of anxiety; this phenomenon is likely associated with the increase in MAOA
expression in the hippocampus.
PMID- 28413108
TI - Moisturisers in scar management following burn: A survey report.
AB - : Scar management is a recognised key component of rehabilitation following burn.
Moisturising often combined with massage is commenced once healing tissue has
gained sufficient strength to tolerate surface friction, with the aim being to
hydrate the dry scar. The studies on various moisturisers and creams provide some
guidance on moisturiser selection, but many are inconclusive. OBJECTIVE: This
survey aimed to determine the current expert opinion regarding moisturiser
recommendations, including the basis for these recommendations, across the burns
community. METHODS: A brief web-based survey was distributed to burn therapists
via mailing lists of the Australian and New Zealand Burn Association (ANZBA), and
American Burn Association (ABA) 'Occupational and Physical Therapist Burn Special
Interest Group'. RESULTS: The fifty three respondents indicated that there were
29 different moisturisers commonly recommended in practice. Three main themes
were indicated as influencing recommendations for moisturiser: the perceived
effects on the scar/skin (48%); the general properties of the moisturiser (38%);
the ingredients (14%). Therapists reported that the principle stimuli determining
their recommendations were patient feedback and the choice of the previous burn
therapist in their service. Many were also guided by medical staff, pharmacists
and sales representatives. Only three respondents were able to provide citations
for published evidence supporting their recommendations. CONCLUSIONS: There is a
paucity of evidence currently to support optimal moisturiser choice. This survey
demonstrates that conflicting opinions are held on the ideal moisturiser brand,
properties and ingredients. The recommendations made are based on low level
evidence. Further research is required to inform clinicians which moisturiser to
recommend to their clients. An ideal moisturiser should be one that is conducive
to scar maturation, non- or minimally irritant, prevent skin drying, minimise
transepidermal water loss and have no negative effect on barrier function.
PMID- 28413109
TI - Development of an integrative algorithm for the treatment of various stages of
full-thickness burns of the first commissure of the hand.
AB - Burns of the first commissure of the hand can evolve into an adduction
contracture of the thumb. We decided to conduct a review of the existing
literature on the treatment of full-thickness burns of the first commissure in
order to develop a treatment algorithm that integrates the various currently
available procedures. A search of the existing literature was conducted, focusing
on the treatment of a burn of the first commissure in its chronic and acute
phases. A total of 29 relevant articles were selected; 24 focused exclusively on
the chronic contracture stage, while 3 focused exclusively on the acute burn
stage, and 2 articles studied both stages. A therapeutic algorithm for full
thickness burns of the first commissure of the hand was developed. With this
algorithm we sought to relate each degree and stage of the burn with a treatment.
PMID- 28413110
TI - Seawater immersion aggravates burn-associated lung injury and inflammatory and
oxidative-stress responses.
AB - With the increasing frequency of marine development activities and local wars at
sea, the incidence of scald burns in marine accidents or wars has been increasing
yearly. Various studies have indicated that immersion in seawater has a systemic
impact on some organs of animals or humans with burn. Thus, for burn/scald
injuries after immersion in seawater, it is desirable to study the effects and
mechanisms of action on important organs. In the present study, we aimed to
investigate the effect of immersion in seawater on lung injury, inflammatory and
oxidative-stress responses in scalded rats. The structural damage to lungs was
detected by hematoxylin and eosin staining and the results showed that seawater
immersion aggravated structural lung injury in scalded rats. The expression of
HMGB1 in lung tissues was detected by immunohistochemical analysis and the
results showed that seawater immersion increased HMGB1 expression in lung tissues
of scalded rats. Apoptosis in lung tissues was detected by terminal
deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and
the results showed that seawater immersion increased apoptosis rate in lung
tissues of scalded rats. In addition, the expression levels of TNF-alpha, IL-6,
IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays
(ELISAs) and the results showed that seawater immersion induced secretion of
proinflammatory factors (TNF-alpha, IL-6, and IL-8), increased MDA protein level,
and suppressed SOD activity in the serum of scalded rats. Furthermore,
measurement of plasma volume and pH showed that seawater immersion decreased
plasma volume and pH value. Overall, the results indicated that all effects
induced by immersion in seawater in scalded rats are more pronounced than those
induced by freshwater. In conclusion, seawater immersion may aggravate lung
injury and enhance inflammatory and oxidative-stress responses after burn.
PMID- 28413111
TI - Comparison of clinical outcomes in diabetic and non-diabetic burns patients in a
national burns referral center in Southeast Asia: A 3-year retrospective review:
Methodological issues.
PMID- 28413112
TI - The effect of negative remodeling on fractional flow reserve after cardiac
transplantation.
AB - BACKGROUND: Negative remodeling is a common occurrence early after cardiac
transplantation. Its impact on the development of myocardial ischemia is not well
documented. The aim of this study is to investigate the impact of negative
remodeling on fractional flow reserve after cardiac transplantation. METHODS:
Thirty-four cardiac transplant recipients underwent intravascular ultrasound
(IVUS) and fractional flow reserve (FFR) assessment soon after transplantation
and one year later. Patients were divided into those with and without negative
remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients
with negative remodeling, there was no significant change in plaque volume
(119.3+/-82.0 to 131.3+/-91.2mm3, p=0.21), but vessel volume (775.6+/-212.0 to
621.9+/-144.1mm3, p<0.0001) and lumen volume (656.3+/-169.1 to 490.7+/-132.0mm3,
p<0.0001) decreased significantly and FFR likewise decreased significantly
(0.88+/-0.06 to 0.84+/-0.07, p=0.04). In the 15 patients without negative
remodeling, vessel volume did not change (711.7+/-217.6 to 745.7+/-198.5,
p=0.28), but there was a significant increase in plaque volume (126.8+/-88.3 to
194.4+/-92.7, p<0.001) and a resultant significant decrease in FFR (0.89+/-0.05
to 0.85+/-0.05, p=0.01). CONCLUSION: Negative remodeling itself, without any
change in plaque volume can cause a significant decrease in fractional flow
reserve after cardiac transplantation and appears to be another possible
mechanism for myocardial ischemia.
PMID- 28413113
TI - Association of low serum albumin concentration and adverse cardiovascular events
in stable coronary heart disease.
AB - OBJECTIVE: Coronary heart disease (CHD) is a leading cause of death in developed
countries. Exploration of indicators to identify high risk individuals who
develop adverse outcomes despite stable baseline condition is important. This
study is to evaluate the association between serum albumin concentration and
cardiovascular (CV) outcomes in individuals of stable CHD. METHODS: Seven-hundred
thirty-four participants from Biosignature study, a nationwide prospective cohort
study aimed to identity risk factors among patients with stable CHD, were
enrolled for analysis. They were divided into low serum albumin group (baseline
albumin concentration <3.5g/dL, n=98) and normal albumin group (baseline albumin
concentration >=3.5g/dL, n=636). The relations between baseline albumin and
adverse CV outcomes within 18months of follow-up were analyzed. RESULTS: Compared
baseline characteristics with normal albumin group, subjects in low albumin group
are older, having more diabetic patients, lower hemoglobin level, lower estimated
glomerular filtration rate, lower total cholesterol level, lower left ventricular
ejection fraction, and higher blood glucose. While there is no significant
difference of total CV events between two groups, low serum albumin concentration
is associated with an increased risk of all-cause mortality (10.2% vs. 0.5%,
p<0.001) and hard CV events (7.1% vs. 1.4%, p<0.001). The association remains
significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95%
CI: 1.01-45.62; hard CV events, HR: 3.68, 95% CI: 1.03-13.19). CONCLUSIONS: Low
serum albumin concentration (<3.5g/dL) worsens prognosis of patients with stable
CHD.
PMID- 28413114
TI - Left atrial appendage thrombi relate to easily accessible clinical parameters in
patients undergoing atrial fibrillation transcatheter ablation: A multicenter
study.
AB - BACKGROUND: Transesophageal echocardiography (TEE) is routinely performed before
atrial fibrillation (AF) transcatheter ablation to exclude the presence of left
atrial (LA) or LA appendage (LAA) thrombi. The aim of the study is to evaluate if
easily accessible clinical parameters may relate to the presence of LA or LAA
thrombi to identify patients who could potentially avoid TEE. METHODS AND
RESULTS: Between January 2012 and September 2014, data from 1539 consecutive
patients undergoing TEE, as a work-up before AF transcatheter ablation, in six
large volume centers were collected. Baseline clinical features, CHA2DS2-VASc
score, transthoracic echocardiography and presence of thrombi at TEE were
recorded. Exclusion criteria were valvular, hypertrophic or dilated
cardiomyopathy, previous heart surgery or an ejection fraction <=35%. Mean age
was 59.6+/-10.4years, 1215 (78.9%) were males; 951 (62.9%) presented in sinus
rhythm (SR) on admission, 324 (21.1%) had undergone at least one previous
ablation and 900 (58.5%) had CHA2DS2-VASc score 0-1. Thrombi were encountered in
12 patients (0.8%). SR at TEE independently related to the absence of thrombi (OR
5.15, 95% CI 1.38-19.02, p=0.015); in addition to this, no patient with a CHA2DS2
VASc score 0-1 and SR on admission presented thrombi at TEE (specificity 100%,
p=0.011). CONCLUSION: In a selected population of patients referred for AF
ablation, LA/LAA thrombi prevalence is low. No patients in SR with CHA2DS2-VASc
score 0-1 presented LAA thrombi at TEE, identifying a significant subset of
patients who could potentially safely be spared from pre-procedural TEE.
PMID- 28413115
TI - Rate of contamination of hospital privacy curtains on a burns and plastic surgery
ward: a cross-sectional study.
AB - BACKGROUND: Surfaces in the patient environment may play a role in microbial
transmission if they become colonized by bacteria. Patient privacy curtains are
one such surface that may pose a high risk for transmission because they are high
contact surfaces, are infrequently cleaned, and healthcare workers are less
likely to wash their hands after contacting inanimate objects such as curtains.
AIM: To determine the amount and type of bacterial colonization of patient
privacy curtains at a regional burns/plastic surgery unit. METHODS: Privacy
curtain contamination on the burns/plastic surgery ward was determined for two
separate occasions six months apart: 23 curtains on August 2015 and 26 curtains
on January 2016. Dey-Engley neutralizing agar (DENA) replicate organism detection
and counting (RODAC) contact plates were used daily to sample curtains near the
edge hem where they are most frequently touched. Microbial contamination was
reported as cfu/cm2 and the presence of meticillin-resistant Staphylococcus
aureus (MRSA) was determined. Swabs were also taken of any open wounds and from
tracheostomy sites on the ward. FINDINGS: Curtain contamination in August 2015
was 0.7-4.7 cfu/cm2 with 22% testing positive for MRSA, whereas contamination on
January 2016 was 0.6-13.3 cfu/cm2 with 31% of curtains testing positive for MRSA.
CONCLUSION: Curtains on the burns/plastic surgery ward become colonized with
significant quantities of bacteria. Future studies will need to address the rate
of colonization and the clinical impact of this colonization to better inform
cleaning protocols.
PMID- 28413116
TI - Trunk Muscle EMG During Intermediate Pilates Mat Exercises in Beginner Healthy
and Chronic Low Back Pain Individuals.
AB - OBJECTIVE: The purpose of this study was to compare the electromyographic pattern
of core muscles during intermediate Pilates mat exercises between healthy people
and those with low back pain. METHODS: We evaluated healthy participants (n = 19;
mean +/- standard deviation [SD]: age 28 +/- 8 years, body mass 65 +/- 10 kg,
height 160.0 +/- 9.1 cm) and a low back pain group (n = 13; mean +/- SD: age 30
+/- 9 years, body mass 67 +/- 12 kg, height 170.0 +/- 6.6 cm). Electromyographic
analysis assessed the multifidus, external oblique, internal oblique, and rectus
abdominis muscles during classical Pilates exercises (single leg stretch, criss
cross, and dead bug). We calculated the root mean square normalized by maximum
voluntary contraction, and the time of peak activation was provided by a linear
envelope and normalized by the total movement cycle. RESULTS: The criss-cross
exercise presented the highest values of root mean square for trunk flexors
(rectus abdominis and oblique) compared with the other exercises, followed by the
single leg stretch and the dead bug, which had similar muscle activation. The
single leg stretch presented more activation of the rectus abdominis and oblique,
whereas the criss-cross and dead bug created more activation of the oblique
compared with the multifidus and rectus. CONCLUSIONS: The Pilates exercises
presented different muscle recruitment patterns, and allowed the activation of
the lumbopelvic stabilizing muscles even in the first session for healthy
individuals and those with chronic low back pain.
PMID- 28413117
TI - Structure-Specific Movement Patterns in Patients With Chronic Low Back
Dysfunction Using Lumbar Combined Movement Examination.
AB - OBJECTIVE: A test-retest cohort study was conducted to assess the use of a novel
computer-aided, combined movement examination (CME) to measure change in low back
movement after pain management intervention in 17 cases of lumbar spondylosis.
Additionally we desired to use a CME normal reference range (NRR) to compare and
contrast movement patterns identified from 3 specific structural pathologic
conditions: intervertebral disc, facet joint, and nerve root compression.
METHODS: Computer-aided CME was used before and after intervention, in a cohort
study design, to record lumbar range of movement along with pain, disability, and
health self-report questionnaires in 17 participants who received image-guided
facet, epidural, and/or rhizotomy intervention. In the majority of cases, CME was
reassessed after injection together with 2 serial self-reports after an average
of 2 and 14 weeks. A minimal clinically important difference of 30% was used to
interpret meaningful change in self-reports. A CME NRR (n = 159) was used for
comparison with the 17 cases. Post hoc observation included subgrouping cases
into 3 discrete pathologic conditions, intervertebral disc, facet dysfunction,
and nerve root compression, in order to report intergroup differences in CME
movement. RESULTS: Seven of the 17 participants stated that a "combined" movement
was their most painful CME direction. Self-report outcome data indicated that 4
participants experienced significant improvement in health survey, 5 improved by
>=30% on low back function, and 8 reported that low back pain was more bothersome
than stiffness, 6 of whom achieved the minimal clinically important difference
for self-reported pain. Subgrouping of cases into structure-specific groups
provided insight to different CME movement patterns. CONCLUSION: The use of CME
assists in identifying atypical lumbar movement relative to an age and sex NRR.
Data from this study, exemplified by representative case studies, provide
preliminary evidence for distinct intervertebral disc, facet joint, and nerve
root compression CME movement patterns in cases of chronic lumbar spondylosis.
PMID- 28413118
TI - Cadaveric and Ultrasonographic Validation of Needling Placement in the Cervical
Multifidus Muscle.
AB - OBJECTIVE: The aim of this study was to determine if a needle is able to reach
the cervical multifidus during the application of dry needling or acupuncture.
METHODS: Dry needling and ultrasound imaging of cervical multifidi was conducted
on 5 patients (age: 32 +/- 5 years) with mechanical neck pain and on 2 fresh
cadavers (age: 64 +/- 1 years). Dry needling was done using a needle of 40 mm in
length inserted perpendicular to the skin about 1 cm lateral to the spinous
process at C3-C4. The needle was advanced from a posterior to anterior direction
into the cervical multifidus with a slight inferior-medial angle (approximately
10 degrees ) to reach the vertebra lamina. For the cadaveric study, the
multifidus was isolated by carefully resecting the superficial posterior cervical
muscles: trapezius, splenius, and semispinalis. For the ultrasonographic study, a
convex transducer was placed transversely over C3-C4 after the insertion of the
needle into the muscle. RESULTS: The results of both the cadaveric and ultrasonic
studies found that the needle does pierce the cervical multifidus muscle during
insertion and that the tip of the needle rests properly against the vertebral
laminae, thereby guarding the sensitive underlying spinal structures from damage.
CONCLUSION: This anatomical and ultrasound imaging study supports that dry
needling of the cervical multifidus could be conducted clinically.
PMID- 28413119
TI - The two Dictyostelium discoideum autophagy 8 proteins have distinct autophagic
functions.
AB - Autophagy is a highly conserved cellular degradation pathway which is crucial for
various cellular processes. The autophagic process is subdivided in the
initiation, autophagosome maturation and lysosomal degradation phases and
involves more than forty core and accessory autophagy-related (ATG) proteins.
Autophagy 8 (ATG8, in mammals LC3) is a well-established marker of autophagy and
is linked to the autophagic membrane from initiation until fusion with the
lysosome. We generated single and double knock-out mutants of the two
Dictyostelium paralogues, ATG8a and ATG8b, as well as strains that expressed RFP
ATG8a and/or GFP-ATG8b, RFP-ATG8b, RFP-GFP-ATG8a or RFP-GFP-ATG8b in different
knock-out mutants. The ATG8b- mutant displayed only subtle phenotypic changes in
comparison to AX2 wild-type cells. In contrast, deletion of ATG8a resulted in a
complex phenotype with delayed development, reduced growth, phagocytosis and cell
viability, an increase in ubiquitinylated proteins and a concomitant decrease in
proteasomal activity. The phenotype of the ATG8a-/b- strain was, except for cell
viability, in all aforementioned aspects more severe, showing that both proteins
function in parallel during most analysed cellular processes. Immunofluorescence
analysis of knock-out strains expressing either RFP-GFP-ATG8a or RFP-GFP-ATG8b
suggests a crucial function for ATG8b in autophagosome-lysosome fusion.
Quantitative analysis of strains expressing RFP-ATG8a, RFP-ATG8b, or RFP-ATG8a
and GFP-ATG8b revealed that ATG8b generally localised to small and large
vesicles, whereas ATG8a preferentially co-localised with ATG8b on large vesicles,
indicating that ATG8b associated with nascent autophagosomes before ATG8a, which
is supported by previous results (Matthias et al., 2016). Deconvoluted confocal
fluorescence images showed that ATG8b localised around ATG8a and was presumably
mainly present on the outer membrane of the autophagosome while ATG8a appears to
be mainly associated with the inner membrane. In summary, our data show that
ATG8a and ATG8b have distinct functions and are involved in canonical as well as
non-canonical autophagy. The data further suggest that ATG8b predominantly acts
as adapter for the autophagy machinery at the outer and ATG8a as cargo receptor
at the inner membrane of the autophagosome.
PMID- 28413120
TI - Endosome to trans-Golgi network transport of Proprotein Convertase 7 is mediated
by a cluster of basic amino acids and palmitoylated cysteines.
AB - Proprotein Convertase 7 (PC7) is a Furin-like endoprotease that cleaves precursor
proteins at basic amino acids. PC7 is concentrated in the trans-Golgi network
(TGN) but it shuttles between the plasma membrane and the TGN depending on
sequences in the cytoplasmic tail. A short region containing a three amino acids
motif, P724-L725-C726, is essential and sufficient for internalization of PC7 but
not for TGN localization, which requires the additional presence of the
juxtamembrane region. In this study we have investigated the contribution of a
cluster of basic amino acids and two reversibly palmitoylated cysteine residues
to endocytic trafficking. Stable cell lines overexpressing chimeric proteins
(CD25 and CD46) containing the cytoplasmic domain of PC7 in which the basic
cluster alone or together with both palmitoylated cysteines are mutated showed
enhanced surface expression as demonstrated by immunofluorescence experiments and
surface biotinylation. The mutant proteins no longer recycled to the TGN in
antibody uptake experiments and accumulated in an endosomal compartment.
Recycling of wild type PC7 to the TGN is blocked by nocodazole, suggesting that
PC7 shuttles to the TGN via late endosomes, similar to Furin. Unlike furin,
however, PC7 was found to recycle to a region within the TGN, which is deficient
in sialyltransferase, as shown by resialylation experiments. In conclusion, a
novel motif, composed of a basic amino acid cluster and two palmitoylated
cysteines are essential for TGN localization and endocytic trafficking.
PMID- 28413121
TI - Characterisation of cell cycle arrest and terminal differentiation in a maximally
proliferative human epithelial tissue: Lessons from the human hair follicle
matrix.
AB - Human hair follicle (HF) growth and hair shaft formation require terminal
differentiation-associated cell cycle arrest of highly proliferative matrix
keratinocytes. However, the regulation of this complex event remains unknown.
CIP/KIP family member proteins (p21CIP1, p27KIP1 and p57KIP2) regulate cell cycle
progression/arrest, endoreplication, differentiation and apoptosis. Since they
have not yet been adequately characterized in the human HF, we asked whether and
where CIP/KIP proteins localise in the human hair matrix and pre-cortex in
relation to cell cycle activity and HF-specific epithelial cell differentiation
that is marked by keratin 85 (K85) protein expression. K85 expression coincided
with loss or reduction in cell cycle activity markers, including in situ DNA
synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1,
affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of
CIP/KIP proteins was found abundantly within the proliferative hair matrix,
concomitant with a role in cell cycle checkpoint control. p21CIP1, p27KIP1 and
cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas
p57KIP2 protein decreased but became nuclear. These data imply a supportive role
for CIP/KIP proteins in maintaining proliferative arrest, differentiation and
anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft
formation in anagen VI. Moreover, post-mitotic hair matrix regions contained
cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were
>2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance
cyclin E to control further rounds of DNA replication in a cell population that
has a propensity to become tetraploid. These data shed new light on the in situ
biography of human hair matrix keratinocytes on their path of active cell
cycling, arrest and terminal differentiation, and showcase the human HF as an
excellent, clinically relevant model system for cell cycle physiology research of
human epithelial cells within their natural tissue habitat.
PMID- 28413122
TI - Letter to the editor: Sepsis-associated in-hospital cardiac arrest: Epidemiology,
pathophysiology, and potential therapies.
PMID- 28413123
TI - Caution using the new "no pain no gain" approach.
PMID- 28413124
TI - Videolaryngoscopy for trauma patient intubation.
PMID- 28413125
TI - Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures
and late reduced diffusion.
AB - Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is
associated with various types of acquired brain injuries. Traumatic brain lesions
have been documented as the leading cause of PSH. However, detailed clinical
features of pediatric PSH caused by intrinsic brain lesions remain to be elusive.
We present a 3-year-old boy, who had been diagnosed as having cerebral palsy,
developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He
developed status epilepticus with fever on the third day of respiratory
infection. Whereas the seizure was terminated by systemic infusion of midazolam,
consciousness remained disturbed for the next 48h. Serial magnetic resonance
imaging studies revealed that acute encephalopathy with biphasic seizures and
late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic
hypothermia was immediately introduced, however, the brain lesion extended to the
whole subcortical white matters on day 8. The intermittent bilateral dilation of
pupils with increased blood pressure and tachycardia were observed until day 12.
Real-time monitoring of electroencephalograms ruled out the recurrent attacks of
seizures. The abnormal signs of autonomic nervous system gradually ceased and
never relapsed after recovery from the hypothermia. PSH or a transient condition
of dysautonomia may emerge and persist during the acute phase of AESD.
PMID- 28413126
TI - Consensus Statement of the European Urology Association and the European
Urogynaecological Association on the Use of Implanted Materials for Treating
Pelvic Organ Prolapse and Stress Urinary Incontinence.
AB - CONTEXT: Surgical nonautologous meshes have been used for several decades to
repair abdominal wall herniae. Implantable materials have been adopted for the
treatment of female and male stress urinary incontinence (SUI) and female pelvic
organ prolapse (POP). OBJECTIVE: A consensus review of existing data based on
published meta-analyses and reviews. EVIDENCE ACQUISITION: This document
summarises the deliberations of a consensus group meeting convened by the
European Association of Urology (EAU) and the European Urogynecological
Association, to explore the current evidence relating to the use of polypropylene
(PP) materials used for the treatment of SUI and POP, with reference to the 2016
EAU guidelines (European Association of Urology 2016), the European Commission's
SCENIHR report on the use of surgical meshes (SCENIHR 2015), other available high
quality evidence, guidelines, and national recommendations. EVIDENCE SYNTHESIS:
Current data suggest that the use of nonautologous durable materials in surgery
has well-established benefits but significant risks, which are specific to the
condition and location they are used for. Various graft-related complications
have been described-such as infection, chronic pain including dyspareunia,
exposure in the vagina, shrinkage, erosion into other organs of xenografts,
synthetic PP tapes (used in SUI), and meshes (used in POP)-which differ from the
complications seen with abdominal herniae. CONCLUSIONS: When considering surgery
for SUI, it is essential to evaluate the available options, which may include
synthetic midurethral slings (MUSs) using PP tapes, bulking agents,
colposuspension, and autologous sling surgery. The use of synthetic MUSs for
surgical treatment of SUI in both male and female patients has good efficacy and
acceptable morbidity. Synthetic mesh for POP should be used only in complex cases
with recurrent prolapse in the same compartment and restricted to those surgeons
with appropriate training who are working in multidisciplinary referral centres.
PATIENT SUMMARY: Synthetic slings can be safely used in the surgical treatment of
stress incontinence in both male and female patients. Patients need to be aware
of the alternative therapy and potential risks and complications of this therapy.
Synthetic mesh for treating prolapse should be used only in complex cases with
recurrent prolapse in specialist referral centres.
PMID- 28413127
TI - Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy
in Metastatic Renal Cell Carcinoma.
AB - BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails
mechanistically distinct agents across the first- and second-line setting.
Activity of these agents may be predicated on selective pressure that modulates
RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively
ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA
profile in a large cohort of mRCC patients, and to assess changes across patients
receiving first-line and later lines of therapy. DESIGN, SETTING, AND
PARTICIPANTS: We obtained the ctDNA profile in mRCC patients who received ctDNA
profiling as part of routine clinical care at progression using a 73-gene
Clinical Laboratory Improvement Amendments-certified ctDNA platform. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Genomic alterations (GAs) were pooled for
the entire cohort. A comparison of first- and postfirst-line was performed with
grouping based on conventional practice patterns (first-line regimens included
sunitinib, pazopanib, and bevacizumab, and postfirst-line regimens included
everolimus, axitinib, cabozantinib, and nivolumab). RESULTS AND LIMITATIONS:
ctDNA clinical results from a nationwide cohort of 220 consecutive patients with
mRCC were assessed (145 men, 75 women; median age: 63 yr, interquartile range: 57
70). GAs were detected in 78.6% of patients. The most frequent GAs in the overall
cohort included TP53 (35%), VHL (23%), EGFR (17%), NF1 (16%), and ARID1A (12%).
Thirty-eight and 64 patients were coded as receiving first-line and later line
agents, respectively. The highest disparity in GA frequencies in postfirst-line
versus first-line were in TP53 (49% vs 24%), VHL (29% vs 18%), NF1 (20% vs 3%),
EGFR (15% vs 8%), and PIK3CA (17% vs 8%) while ARID1A was equivalent (13% vs
11%). Restricting the analysis to later lines versus first-line vascular
endothelial growth factor inhibitors, these differences were even more prominent,
particularly for TP53 (64% vs 31%) and NF1 (29% vs 4%). CONCLUSIONS: In the
largest assessment of ctDNA-detected GAs prevalence in mRCC to date, the majority
of patients demonstrated clinically and biologically relevant GAs. Increasing p53
and mechanistic target of rapamycin pathway (eg, NF1, PIK3CA) alterations in
postfirst-line patients with first-line vascular endothelial growth factor
directed therapy may underlie mechanisms of resistance. Routine ctDNA assessment
during the clinical course of mRCC patients may have therapeutic implications.
PATIENT SUMMARY: Collection of circulating tumor DNA is feasible in patients with
metastatic renal cell carcinoma, and analysis of a large cohort demonstrates
significant changes in circulating tumor DNA profile across patients' clinical
course which may have therapeutic implications.
PMID- 28413128
TI - Immune Checkpoint Inhibition in Metastatic Urothelial Cancer.
AB - Immune checkpoint inhibitors are a new treatment option in metastatic urothelial
cancer on the basis of available phase 2 and 3 trials. Predictive biomarkers are
needed. These should go beyond PD-L1 expression, which is showing inconsistent
results across trials.
PMID- 28413129
TI - Return to Play After Osteochondral Autograft Transplantation of the Capitellum: A
Systematic Review.
AB - PURPOSE: To determine the rate of return to play and to identify lesion or
osteochondral graft characteristics that may influence the return to competitive
athletics after osteochondral autograft transplantation (OAT) for symptomatic
osteochondritis dissecans (OCD) lesions. METHODS: A systematic review was
conducted according to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines. A duplicate search of PubMed, Embase, Scopus, Web of
Science, and CENTRAL databases was performed, beginning from the database
inception dates through July 2016, for all articles evaluating the return to play
after OAT for OCD lesions of the capitellum. A methodological quality assessment
was completed for all included studies. Patient demographics, osteochondral
lesion and graft characteristics, the number of patients, and timing of return to
competitive activity were collected and evaluated. Association between graft
size/number, the time to osseous healing, and return to sport was evaluated.
RESULTS: Seven articles met the inclusion criteria. All included studies were
case series of moderate quality with a mean Methodological Index for Non
Randomized Studies score of 12/16. Overall, 94% (119/126) of patients undergoing
OAT for OCD lesions of the capitellum successfully returned to competitive
sports. The mean reported time for unrestricted return to athletic competition
after OAT was 5.6 months (range, 3-14 months). CONCLUSIONS: Current best evidence
suggests that OAT is successful in treating advanced OCD lesions of the
capitellum and returning athletes to high-level competition. Evidence supporting
the association between the size and number of grafts used and the time to
osseous healing and return to sport is currently limited. Our assessment of the
time to return to athletic competition was limited because of variable surgical
technique, postoperative rehabilitation protocols, and outcome assessment. LEVEL
OF EVIDENCE: Level IV, systematic review of Level IV studies.
PMID- 28413130
TI - Arthroscopic Treatment of Labral Tears of the Hip in Adolescents: Patterns of
Clinical Presentation, Intra-articular Derangements, Radiological Associations
and Minimum 2-Year Outcomes.
AB - PURPOSE: To report on patterns of clinical presentation, intra-articular
derangements, radiological associations, and minimum 2-year outcomes after hip
arthroscopy (HA) in patients 18 years or younger. METHODS: This study was a
retrospective case series on patients 18 years or younger who had undergone HA
for labral tears that had failed nonoperative management from April 2008 to April
2013 with a minimum 2-year follow-up. Exclusion criteria were previous hip
conditions or surgery. The following were recorded: demographic, examination,
radiological and intraoperative findings, intraoperative procedures performed,
patient-reported outcomes (PROs), and patient satisfaction. The PROs reported
included the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome
Score-Sport-Specific Subscale, Hip Outcome Score-Activities of Daily Living, and
Visual Analogue Score for pain. RESULTS: One hundred and two patients satisfied
the inclusion criteria, of whom 90 (88.2%, 77 females and 13 males) had minimum 2
year follow-up. Females had increased external rotation in flexion (58.9 degrees
vs 50.0 degrees , P = .041). Sixty-eight females had a Beighton's score of >4
compared to 6 males (P < .001). There was no distinct pattern within the group or
between genders for radiological markers of acetabular coverage, depth, or
version and femoral cam size. Mean femoral anteversion for females was 15.7
degrees and for males 11.3 degrees . Females had significantly smaller labral
tears (1.73 hours vs 2.34 hours on the acetabular clock face, P = .028). Females
were more likely to require a capsular plication and iliopsoas fractional
lengthening (88.3% vs 46.2%, and 77.9% vs 38.5%, respectively). There was a
significant improvement in all PRO measures in both males and females (P < .01),
but females had lower preoperative and postoperative scores. Mean preoperative
and postoperative PROs for males and females were as follows: modified Harris Hip
Score 71.0/94.3 and 63.4/88.8, Hip Outcome Score-Activities of Daily Living
78.1/93.4 and 64.0/91.8, Hip Outcome Score-Sport-Specific Subscale 51.7/91.0 and
45.7/78.6, Non-Arthritic Hip Score 78.1/94.5 and 63.1/89.2, and visual analog
score 4.77/1.85 and 6.29/2.21. The mean patient satisfaction score was 8.29 out
of 10. Five patients (5.56%) required a revision procedure. CONCLUSIONS: HA is
associated with improved outcomes and pain and high satisfaction scores at
minimum 2-year follow-up in adolescent population. The pattern of labral injury
is different in males and females and dictates the arthroscopic approach. Females
are likely to require a capsular plication and iliopsoas release to address soft
tissue laxity and impingement. LEVEL OF EVIDENCE: Level IV, therapeutic case
series.
PMID- 28413131
TI - Distress=stress? Disentangling the different components of emotional experience.
PMID- 28413132
TI - Development of an intradermal DNA vaccine delivery strategy to achieve single
dose immunity against respiratory syncytial virus.
AB - Respiratory syncytial virus (RSV) is a massive medical burden in infants,
children and the elderly worldwide, and an effective, safe RSV vaccine remains an
unmet need. Here we assess a novel vaccination strategy based on the intradermal
delivery of a SynCon(r) DNA-based vaccine encoding engineered RSV-F antigen using
a surface electroporation device (SEP) to target epidermal cells, in clinically
relevant experimental models. We demonstrate the ability of this strategy to
elicit robust immune responses. Importantly we demonstrate complete resistance to
pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A
challenge model. In contrast to the formalin-inactivated RSV (FI-RSV) vaccine,
there was no enhanced lung inflammation upon virus challenge after DNA
vaccination. In summary the data presented outline the pre-clinical development
of a highly efficacious, tolerable and safe non-replicating vaccine delivery
strategy.
PMID- 28413133
TI - Vaccination with the polymorphic membrane protein A reduces Chlamydia muridarum
induced genital tract pathology.
AB - Chlamydia trachomatis serovars D-K are one of the most frequent causes of
sexually transmitted infections of the female genital tract, with possible
complications such as hydrosalpinx, pelvic inflammatory disease, extra-uterine
gravidity or infertility. We used the murine genital tract infection model with
C. muridarum for vaccination studies and found that more than 70% of the infected
mice suffered from uterus dilatations and/or hydrosalpinx. Systemic consequences
of the vaginal infection were apparent by splenomegaly ten to fifteen days post
infection. While cultivable microorganisms were detectable for the first 23days
post infection, the first lesions of the genital tract developed at day 15,
however, many lesions occurred later in the absence of cultivable bacteria.
Lesions were not accompanied by pro-inflammatory cytokines such as IFNgamma, TNF
and IL-6, since these cytokines were almost undetectable in the genital tract
43days post infection. To prevent genital tract lesions, we vaccinated mice with
the polymorphic membrane protein (Pmp) A in combination with CpG-ODN 1826 as
adjuvant. The vaccine lowered the chlamydial burden and the differences were
significant at day 10 post infection but not later. More importantly the vaccine
decreased the rate and severity of genital tract lesions. Interestingly, control
vaccination with the protein ovalbumin plus CpG-ODN 1826 enhanced significantly
the severity but not the rate of pathologic lesions, which was presumably caused
by the activation of innate immune responses by the adjuvant in the absence of a
C. muridarum-specific adaptive immune response. In summary, vaccination with
recombinant PmpA plus CpG-ODN 1826 significantly reduced C. muridarum-induced
tissue damage, however, CpG-ODN 1826 may aggravate C. muridarum-induced tissue
injuries in the absence of a protective antigen.
PMID- 28413134
TI - The in vitro MIMIC(r) platform reflects age-associated changes in immunological
responses after influenza vaccination.
AB - Increasing research and development costs coupled with growing concerns over
healthcare expenditures necessitate the generation of pre-clinical testing models
better able to predict the efficacy of vaccines, drugs and biologics. An ideal
system for evaluating vaccine immunogenicity will not only be reliable but also
physiologically relevant, able to be influenced by immunomodulatory
characteristics such as age or previous exposure to pathogens. We have previously
described a fully autologous human cell-based MIMIC(r) (Modular IMmune In vitro
Construct) platform which enables the evaluation of innate and adaptive immunity
in vitro, including naive and recall responses. Here, we establish the ability of
this module to display reduced antibody production and T cell activation upon in
vitro influenza vaccination of cells from elderly adults. In the MIMIC(r) system,
we observe a 2.7-4.2-fold reduction in strain-specific IgG production to seasonal
trivalent influenza vaccine (TIV) in the elderly when compared to adults, as well
as an age-dependent decline in the generation of functional antibodies. A
parallel decline in IgG production with increasing age was detected via short
term ex vivo stimulation of B cells after in vivo TIV vaccination in the same
cohort. Using MIMIC(r), we also detect a reduction in the number but not
proportion of TIV-specific multifunctional CD154+IFNgamma+IL-2+TNFalpha+ CD4+ T
cells in elderly adults. Inefficient induction of multifunctional helper T cells
with TIV stimulation in MIMIC(r) despite a normalized number of initial CD4+ T
cells suggests a possible mechanism for an impaired anti-TIV IgG response in
elderly adults. The ability of the MIMIC(r) system to recapitulate differential
age-associated responses in vitro provides a dynamic platform for the testing of
vaccine candidates and vaccine enhancement strategies in a fully human model
including the ability to interrogate specific populations, such as elderly
adults.
PMID- 28413135
TI - A systematic review of the diagnosis and treatment of patients with neurogenic
hyperactivity of the detrusor muscle.
AB - BACKGROUND: Neurogenic detrusor hyperactivity (NDH) is a urodynamic observation
characterised by involuntary detrusor contractions during the filling phase that
are caused by an underlying neurological disease. The common and severe
complications that can result from NDH warrant the preparation of healthcare
protocols for the proper management of patients with NDH. OBJECTIVE: The aim of
this study is to standardise the criteria for the decision-making process in the
management of patients with diagnosed or suspected NDH, providing personalised
medical care. ACQUISITION OF EVIDENCE: We performed a systematic noncomprehensive
literature review on the aspects of the diagnosis and treatment of NDH. Based on
the review, recommendations were issued by nominal consensus of a group of
urology specialists. SYNTHESIS OF THE EVIDENCE: In general, the diagnosis of NDH
is arrived at by a proper review of the medical history, physical examination and
voiding diary before performing any diagnostic study. The main treatment
objectives are to protect the upper urinary tract, restore function of the lower
tract and improve these patients' continence and quality of life. The treatment
consists of several steps aimed at obtaining proper bladder storage that allows
for sufficiently spaced voidings. The follow-up should be personalised based on
each patient's needs. CONCLUSIONS: The identification and management of NDH is
important for positively redirecting the function of the lower urinary tract, in
terms of filling and voiding, thereby improving the patients' quality of life.
PMID- 28413136
TI - Opioid Use After Total Knee Arthroplasty: Trends and Risk Factors for Prolonged
Use.
AB - BACKGROUND: The United States is in the midst of an opioid epidemic. Little is
known about perioperative opioid use for total knee arthroplasty (TKA). The
purpose of this study was to identify rates of preoperative opioid use, evaluate
postoperative trends and identify risk factors for prolonged use after TKA.
METHODS: Patients who underwent primary TKA from 2007-2014 were identified within
the Humana database. Postoperative opioid use was measured by monthly
prescription refill rates. A preoperative opioid user (OU) was defined by history
of opioid prescription within 3 months prior to TKA and a non-opioid user (NOU)
was defined by no history of prior opioid use. Rates of opioid use were trended
monthly for one year postoperatively for all cohorts. RESULTS: 73,959 TKA
patients were analyzed and 23,532 patients (31.2%) were OU. OU increased from
30.1% in 2007 to 39.3% in 2014 (P < .001). Preoperative opioid use was the
strongest predictor for prolonged opioid use following TKA, with OU filling
significantly more opioid prescriptions than NOU at every time point analyzed.
Younger age, female sex and other intrinsic factors were found to significantly
increase the rate of opioid refilling following TKA throughout the postoperative
year. CONCLUSION: Approximately one-third of TKA patients use opioids within 3
months prior to surgery and this percentage has increased over 9% during the
years included in this study. Preoperative opioid use was most predictive of
increased refills of opioids following TKA. However, other intrinsic patient
characteristics were also predictive of prolonged opioid use.
PMID- 28413137
TI - Response to Letter to the Editor on "Efficacy in Deep Vein Thrombosis Prevention
With Extended Mechanical Compression Device Therapy and Prophylactic Aspirin
Following Total Knee Arthroplasty: A Randomized Control Trial".
PMID- 28413138
TI - Letter to the Editor on "Efficacy in Deep Vein Thrombosis Prevention With
Extended Mechanical Compression Device Therapy and Prophylactic Aspirin Following
Total Knee Arthroplasty: A Randomized Control Trial".
PMID- 28413139
TI - Evaluation of Extensor Mechanism in Revision Knee Arthroplasty.
AB - BACKGROUND: The success of revision total knee arthroplasty depends on adequate
exposure that does not produce complications. The purpose of this study was to
compare the results of revision total knee arthroplasty between V-Y
quadricepsplasty (QP) and quadriceps snip (QS) approaches. METHODS: In the study,
92 knees with follow-up of 12-108 months which were operated by using QP (55) and
QS (37) were evaluated retrospectively. Measurements were taken by using
universal transparent goniometer, also varus valgus deformities, knee flexion
angles, instability, Hospital for Special Surgery and Lower Extremity Functional
Scale scores, functional condition of the knee and activity levels of the
patients were evaluated cross-sectionally. RESULTS: Statistically significant
difference was not found regarding extensor restriction, varus or valgus
deformities, knee flexion angles, flexor and extensor muscular strength, Hospital
for Special Surgery and Lower Extremity Functional Scale score (P > .05).
CONCLUSION: QP is a preferable method which allows a wider arthrotomy for stiff
knees and revision knee surgery, and provides larger access to the joint.
Choosing this incision does not bring disadvantage in terms of extensor
mechanism.
PMID- 28413140
TI - Is Day of Surgery Associated With Adverse Clinical and Economic Outcomes
Following Primary Total Knee Arthroplasty?
AB - BACKGROUND: As orthopedics transition to value-based purchasing, hospitals and
providers are incentivized to identify inefficiencies of care delivery. In our
experience, weekends are characterized by decreased staffing of ancillary
services to coordinate patient discharges, which can lead to prolonged hospital
stays for many of our primary total knee arthroplasty (TKA) admissions. METHODS:
We identified 115,053 patients who underwent primary TKA on a weekday between
2009 and 2013 in New York State. We used mixed effects regression models to
compare length of stay (LOS), 90-day readmission, and cost according to the day
of TKA. RESULTS: Mean LOS was significantly higher for surgeries performed on
Wednesday (P < .001), Thursday (P < .001), and Friday (P < .001). There was no
significant difference in 90-day readmission risk according to day of surgery.
Mean cost was significantly higher for surgeries performed on Wednesday (P <
.001), Thursday (P < .001), and Friday (P < .001). When LOS was held constant
across every day of the week, the mean cost of TKA decreased by $247 for
Wednesday, $627 for Thursday, and $394 for Friday. CONCLUSION: Primary TKA
performed later in the week is associated with an increased LOS and increased
costs of admission, but a similar risk of 90-day readmission. Preferential
scheduling of primary TKA cases early in the week, as well as the development of
standardized clinical care pathways with appropriate weekend staffing of social
work and rehabilitation services, could help to decrease the daily variation in
LOS and increase the value of TKA episodes.
PMID- 28413141
TI - Response to Letter to the Editor on "Patient Reported Kneeling Ability in Fixed
and Mobile Bearing Knee Arthroplasty".
PMID- 28413142
TI - Outcomes of Modular Dual Mobility Acetabular Components in Revision Total Hip
Arthroplasty.
AB - BACKGROUND: There is a high rate of dislocation after revision total hip
arthroplasty. This study evaluated the outcomes of 1 modular dual mobility
component in revision total hip arthroplasty in patients at high risk of
dislocation. METHODS: We reviewed 64 revisions performed in 27 (42%) patients for
recurrent dislocation, 16 (25%) for adverse local tissue reaction, 11 (17%) for
reimplantation infection, and 10 (16%) for aseptic loosening, malposition, or
fracture. Complications, reoperations, and survivorship were evaluated. RESULTS:
Three-year survival was 98% with failure defined as aseptic loosening and 91%
with failure as cup removal for any reason. With mean follow-up time of 38
months, there were 14 complications, including 2 dislocations treated with closed
reduction, 9 infections, and 12 reoperations. All complications occurred in
patients revised for instability, adverse local tissue reaction, or infection.
CONCLUSION: The early results of this component are promising, with good overall
survival and low rate of dislocation.
PMID- 28413143
TI - Arab American Health in a Racially Charged U.S.
PMID- 28413144
TI - [A health system ill at ease with itself].
PMID- 28413145
TI - Body piercing and tattooing among French patients with bleeding disorders.
PMID- 28413146
TI - [Multiple ground-glass opacities nodules].
AB - INTRODUCTION: Ground-glass opacities nodules are frequently detected with the
advances of radiological imaging. These can be preinvasive lesions such as
atypical adenomatous hyperplasia but also invasive lesions. It leads to question
in patients with lung cancer about treatment strategy and follow up. CASE REPORT:
We report the case of a 72 years-old woman followed for a lung adenocarcinoma
with an EGFR mutation of the right upper lobe stage IIb. The CT scan shows
multiple pure ground-glass opacities in the same lobe of the primitive tumor but
also in the other lobe. On the piece of lobectomy, histopathology of two ground
glass opacities showed atypical adenomatous hyperplasia. CONCLUSION: Ground-glass
opacities nodules could be found in patients with an operable lung cancer. These
can be multiple and match with atypical adenomatous hyperplasia but also
carcinomas lesions. The radiological surveillance is still the standard. The
strategy for surgical resection has to be defined especially in case of multiple
lesions which can require repeated surgical resection.
PMID- 28413147
TI - Branchial cleft cyst: An unusual site for the cervical metastasis of
nasopharyngeal carcinoma.
AB - OBJECTIVE: Cancers found in the resected branchial cleft cyst are rare clinically
but usually impose substantive diagnostic and treatment challenges for
clinicians. METHODS: A 31-year-old man presented with a lateral neck mass that
was suspected to be an inflammatory branchial cleft cyst. After excision, the
pathologic specimen revealed a benign cystic appearance with a focus of
undifferentiated carcinoma. Serologic tests for Epstein-Barr virus were negative.
A positron emission tomography scan and upper aerodigestive tract endoscopies
were negative for any other suspicious lesion. RESULTS: The patient underwent
random biopsies of the nasopharynx, tongue base, and hypopharynx and bil
tonsillectomy. Pathologic examination of the nasopharyngeal biopsies showed the
presence of undifferentiated carcinoma. The cancerous part of the branchial cleft
cyst and this nasopharyngeal specimen were positive for the latent membrane
protein-1 and EBV-encoded RNAs of Epstein-Barr virus (EBV) and confirmed our
diagnosis. CONCLUSION: This is the first report of a NPC metastasizing to a
branchial cleft cyst. Molecular diagnostic techniques facilitate the definite
diagnosis that enabled us to refine treatment plans and offered the patient a
favorable outcome.
PMID- 28413148
TI - Incorporating Site-less Clinical Trials Into Drug Development: A Framework for
Action.
AB - PURPOSE: Options for leveraging available telemedicine technologies, ranging from
simple webcams and telephones to smartphone apps and medical-grade wearable
sensors, are evolving faster than the culture of clinical research. Until
recently, most clinical trials relied on paper-based processes and technology.
This cost- and labor-intensive system, while slowly changing, remains an obstacle
to new drug development. Alternatives that use existing tools and processes for
collecting real-world data in home settings warrant closer examination. METHODS:
The site-less clinical research organization (CRO) model, whereby pharmacists or
other health care professionals provide useful and timely counseling for protocol
compliance by regular phone and videoconferencing sessions, is a flexible
approach to managing clinical trial participants directly from their homes. An
expert panel, including clinical specialists in metabolic or neurodegenerative
diseases, health information technology and CRO innovators, and the
pharmaceutical industry, met in Dallas, Texas, December 2016, to discuss
advancing avenues for site-less CRO and other remote clinical trial practices,
taking into account investigator, sponsor, and regulatory perspectives. FINDINGS:
Real-time "site-less" management of clinical trials can augment traditional
research and development methods by providing data from a broader, more diverse
group of patients in real-world practice settings. This methodology also helps to
proactively identify safety profile and operational issues. Current use of site
less CRO practices constitutes an important bridge to alternative trial models,
including "large simple trials" that strive to answer one or two questions using
data derived from representative patient populations treated in typical clinical
settings. IMPLICATIONS: Site-less CROs offer a working example of how remote
technologies and in-home monitoring methods can address shortcomings of
conventional drug development. This model maximizes time and cost, as well as
potentially earlier identification of adverse events. Coordinated communication
among investigators, sponsors, regulators, and patients will be needed to develop
standardized strategies for incorporating site-less CROs into current and future
study design.
PMID- 28413150
TI - Nerve Conduits-Necessity or Nicety?
PMID- 28413149
TI - Association of Temporomandibular Joint Pain According to Magnetic Resonance
Imaging Findings in Temporomandibular Disorder Patients.
AB - PURPOSE: This study investigated the associations between magnetic resonance
imaging (MRI) findings and pain in the temporomandibular joint (TMJ). MATERIALS
AND METHODS: The study included 646 TMJs of 323 consecutive patients with
temporomandibular disorders; of these, 222 (34.4%) had TMJ pain whereas 424
(65.6%) had no TMJ pain. MRIs were used to evaluate disc position,
osteoarthritis, joint fluid, and bone marrow edema. Internal derangement was
classified as normal, anterior disc displacement with reduction, and anterior
disc displacement without reduction (ADDWOR); condylar morphology was classified
as normal, moderate bony change, and severe bony change. The odds ratio (OR) for
each MRI variable for nonpainful versus painful TMJs was computed using logistic
regression analysis. RESULTS: Compared with joints with normal disc position, the
OR of those with ADDWOR was 2.74 (P < .001) for TMJ pain. Similarly, compared
with joints with normal condylar morphology, the OR of those with severe bony
change was 4.62 (P = .02) for TMJ pain. In addition, the risk of TMJ pain
increased by 2.37 in joints with joint fluid (P < .001) and by 2.34 in joints
with bone marrow edema (P = .006). The risk of TMJ pain increased significantly
with ADDWOR in combination with severe bony change, joint fluid, and bone marrow
edema. CONCLUSIONS: These results suggest an association between TMJ pain and
ADDWOR, severe bony change, joint fluid, and bone marrow edema. Thus, combining
various MRI variables may improve the diagnostic accuracy of TMJ pain.
PMID- 28413151
TI - Public and Patient Knowledge About Dental Implants.
AB - PURPOSE: The more informed a patient is about a given procedure, the better the
ultimate outcome. This study was designed to compare general public awareness and
knowledge regarding oral implant treatment with those of patients presenting for
such treatment and to determine the sources from which they may have obtained
such information, as well as the accuracy of the information. PATIENTS AND
METHODS: In this cross-sectional study, 2 groups of patients were asked to
complete a questionnaire containing implant knowledge questions and questions
regarding any sources they may have used to obtain information about dental
implants. Group I consisted of patients presenting for treatment of a dental
emergency (general population group), and group II consisted of patients
presenting for an implant consultation. The chi2 test was used to determine
whether there were differences in knowledge and information sources between the 2
groups. RESULTS: A total of 126 adult patients (76 dental emergency patients and
50 implant consultation patients) participated in the study. The general
population group was less informed about dental implants, especially information
relating to implant material and longevity, and received information from less
reliable sources than patients presenting for implant screening (friends or
relatives vs primary dentist). Both groups reported cost of the procedure as a
primary barrier to receiving implants (89% and 90%). CONCLUSIONS: There is still
a need for continued education of the general public regarding dental implants.
PMID- 28413152
TI - Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor
Prognosis in Patients With Tongue Squamous Cell Carcinoma.
AB - PURPOSE: The aim of this study was to detect the relationship between phosphatase
and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and
correlate PTEN expression with important clinical parameters of patients with
tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: In this
retrospective case series, all TSCC patients treated at Tianjin Medical
University Cancer Institute and Hospital between March 2005 and October 2011 were
retrospectively reviewed. Demographic information and clinical data (histologic
type, clinical stage, tumor differentiation, and so on) were collected. The miR
24 level was detected by quantitative reverse transcription-polymerase chain
reaction. The PTEN level was analyzed by immunohistochemistry and quantitative
reverse transcription-polymerase chain reaction. Data analyses were performed by
Spearman correlation analysis, Pearson chi2 test, and paired t test. Kaplan-Meier
curves, log-rank analyses, and a Cox proportional hazards model were used to
evaluate the prognostic value of PTEN. RESULTS: A total of 90 patients (aged 59.4
+/- 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was
detected in 28 of 90 tumors (31.1%). The PTEN messenger RNA level was negatively
correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was
negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore,
PTEN expression was significantly lower in cancer tissues than in adjacent normal
tissues, and its expression was negatively correlated with clinical stage (P <
.01) and positively correlated with differentiation (P < .05) in TSCC patients.
In addition, the Kaplan-Meier curve indicated that loss of PTEN expression
resulted in poor survival of TSCC patients (P < .01). Multivariate analysis
indicated that PTEN expression level and clinical stage may be independent
prognostic factors for TSCC patients. CONCLUSIONS: This study suggested that PTEN
expression was negatively correlated with the miR-24 level in TSCC. The loss of
PTEN expression may serve as a predictor of unfavorable prognosis for TSCC
patients.
PMID- 28413153
TI - Contribution by CGG Aitken to discussion of Meuwly et al. (2016).
PMID- 28413154
TI - Is Withaferin A, a magic bullet for metabolic syndrome?
PMID- 28413155
TI - Effects of natural environment on reproductive histo-morphometric dynamics of
female dromedary camel.
AB - Camel shows a seasonal breeding pattern with enhanced reproductive activity
during the period of low climatic temperature, high rainfall and better food
conditions. Therefore, the study was conducted to explore the underlying seasonal
effects on histological dimensions of reproductive tract in adult female one
humped camel (Camelus dromedarius) kept in the natural environment of Pakistan. A
total 25 reproductive tracts were collected during spring, summer, autumn and
winter seasons and were analysed for histo-morphometric parameters during
different environmental conditions. A significant increase in number (p<0.05) and
size (p<0.05) of surface with secondary and tertiary ovarian follicles was
observed in winter season. The epithelial height (p<0.05) and luminal diameter
(p<0.05) of infundibulum, ampulla and isthmus of uterine tubes were also
significantly increased during winter season. Moreover, significantly increased
length (p<0.05) and circumference (p<0.05) of uterine cornua, increased number
(p<0.001) and diameter (p<0.001) of endometrial glands with enlarged surface and
glandular epithelia (p<0.001) were found in winter compared to summer season.
Therefore, we concluded that quiescent ovarian follicular and uterine glandular
activities are the main reason of camel low breeding during summer season.
PMID- 28413156
TI - Exposure of the Amino Terminus of Tau Is a Pathological Event in Multiple
Tauopathies.
AB - Pathological changes to the tau protein, including conformational changes and
aggregation, are major hallmarks of a group of neurodegenerative disorders known
as tauopathies. Among the conformational changes are alterations involving the
extreme amino terminus of the protein, known as the phosphatase-activating domain
(PAD). Aberrant PAD exposure induces a signaling cascade that leads to disruption
of axonal transport, a critical function for neuronal survival. Conformational
display of PAD is an early marker of pathological tau in Alzheimer disease (AD),
but its role in other tauopathies has yet to be firmly established. We used a
relatively novel N-terminal, conformation-sensitive antibody, TNT2, to determine
whether misfolding in the amino terminus (ie, PAD exposure) occurs in non-AD
tauopathies. We found that TNT2 specifically labeled pathological tau in post
mortem human brain tissue from Pick disease, progressive supranuclear palsy,
corticobasal degeneration, and chronic traumatic encephalopathy, but did not
label nonpathological, parenchymal tau. Tau13, another N-terminal antibody, was
not sensitive to pathological N-terminal conformations. Tau13 did not readily
distinguish between normal (ie, parenchymal tau) and pathological tau species and
showed a range of effectiveness at identifying tau pathologies in the non-AD
tauopathies. These findings demonstrate that the conformational display of the
PAD in tau represents a common pathological event in many tauopathies.
PMID- 28413157
TI - Long-term stabilisation of myeloma with curcumin.
AB - Myeloma is a haematological malignancy which typically follows a relapsing
remitting course. While treatment can control the myeloma and improve quality of
life for given periods of time, remissions generally become progressively shorter
with subsequent relapses, and patients ultimately enter a final refractory phase.
To help control symptoms and enhance quality of life, some patients use
complementary therapies as an adjunct to their conventional therapy. Here, we
describe a myeloma patient who started a daily dietary supplement of curcumin
when approaching her third relapse. In the absence of further antimyeloma
treatment, the patient plateaued and has remained stable for the last 5 years
with good quality of life.
PMID- 28413158
TI - Inferring Demographic History Using Two-Locus Statistics.
AB - Population demographic history may be learned from contemporary genetic variation
data. Methods based on aggregating the statistics of many single loci into an
allele frequency spectrum (AFS) have proven powerful, but such methods ignore
potentially informative patterns of linkage disequilibrium (LD) between
neighboring loci. To leverage such patterns, we developed a composite-likelihood
framework for inferring demographic history from aggregated statistics of pairs
of loci. Using this framework, we show that two-locus statistics are more
sensitive to demographic history than single-locus statistics such as the AFS. In
particular, two-locus statistics escape the notorious confounding of depth and
duration of a bottleneck, and they provide a means to estimate effective
population size based on the recombination rather than mutation rate. We applied
our approach to a Zambian population of Drosophila melanogaster Notably, using
both single- and two-locus statistics, we inferred a substantially lower
ancestral effective population size than previous works and did not infer a
bottleneck history. Together, our results demonstrate the broad potential for two
locus statistics to enable powerful population genetic inference.
PMID- 28413159
TI - The Hippo Pathway Maintains the Equatorial Division Plane in the Ciliate
Tetrahymena.
AB - The mechanisms that govern pattern formation within the cell are poorly
understood. Ciliates carry on their surface an elaborate pattern of cortical
organelles that are arranged along the anteroposterior and circumferential axes
by largely unknown mechanisms. Ciliates divide by tandem duplication: the cortex
of the predivision cell is remodeled into two similarly sized and complete
daughters. In the conditional cdaI-1 mutant of Tetrahymena thermophila, the
division plane migrates from its initially correct equatorial position toward the
cell's anterior, resulting in unequal cell division, and defects in nuclear
divisions and cytokinesis. We used comparative whole genome sequencing to
identify the cause of cdaI-1 as a mutation in a Hippo/Mst kinase. CdaI is a
cortical protein with a cell cycle-dependent, highly polarized localization.
Early in cell division, CdaI marks the anterior half of the cell, and later
concentrates at the posterior end of the emerging anterior daughter. Despite the
strong association of CdaI with the new posterior cell end, the cdaI-1 mutation
does not affect the patterning of the new posterior cortical organelles. We
conclude that, in Tetrahymena, the Hippo pathway maintains an equatorial position
of the fission zone, and, by this activity, specifies the relative dimensions of
the anterior and posterior daughter cell.
PMID- 28413160
TI - Interaction Between Familial Transmission and a Constitutively Active Immune
System Shapes Gut Microbiota in Drosophila melanogaster.
AB - Resident gut bacteria are constantly influencing the immune system, yet the role
of the immune system in shaping microbiota composition during an organism's life
span has remained unclear. Experiments in mice have been inconclusive due to
differences in husbandry schemes that led to conflicting results. We used
Drosophila as a genetically tractable system with a simpler gut bacterial
population structure streamlined genetic backgrounds and established cross
schemes to address this issue. We found that, depending on their genetic
background, young flies had microbiota of different diversities that converged
with age to the same Acetobacteraceae-dominated pattern in healthy flies. This
pattern was accelerated in immune-compromised flies with higher bacterial load
and gut cell death. Nevertheless, immune-compromised flies resembled their
genetic background, indicating that familial transmission was the main force
regulating gut microbiota. In contrast, flies with a constitutively active immune
system had microbiota readily distinguishable from their genetic background with
the introduction and establishment of previously undetectable bacterial families.
This indicated the influence of immunity over familial transmission. Moreover,
hyperactive immunity and increased enterocyte death resulted in the highest
bacterial load observed starting from early adulthood. Cohousing experiments
showed that the microenvironment also played an important role in the structure
of the microbiota where flies with constitutive immunity defined the gut
microbiota of their cohabitants. Our data show that, in Drosophila,
constitutively active immunity shapes the structure and density of gut
microbiota.
PMID- 28413161
TI - Rapid and Recent Evolution of LTR Retrotransposons Drives Rice Genome Evolution
During the Speciation of AA-Genome Oryza Species.
AB - The dynamics of long terminal repeat (LTR) retrotransposons and their
contribution to genome evolution during plant speciation have remained largely
unanswered. Here, we perform a genome-wide comparison of all eight Oryza AA
genome species, and identify 3911 intact LTR retrotransposons classified into 790
families. The top 44 most abundant LTR retrotransposon families show patterns of
rapid and distinct diversification since the species split over the last ~4.8 MY
(million years). Phylogenetic and read depth analyses of 11 representative
retrotransposon families further provide a comprehensive evolutionary landscape
of these changes. Compared with Ty1-copia, independent bursts of Ty3-gypsy
retrotransposon expansions have occurred with the three largest showing
signatures of lineage-specific evolution. The estimated insertion times of 2213
complete retrotransposons from the top 23 most abundant families reveal divergent
life histories marked by speedy accumulation, decline, and extinction that
differed radically between species. We hypothesize that this rapid evolution of
LTR retrotransposons not only divergently shaped the architecture of rice genomes
but also contributed to the process of speciation and diversification of rice.
PMID- 28413163
TI - ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride
clearance.
AB - Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of
LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two
ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity
and increases serum TG independent of ANGPTL8. These effects are reversed with an
ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a
functional inhibitory motif, is inactive by itself and requires ANGPTL3
expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3
that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not
required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3
and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3
alone, suggesting the major inhibitory activity of this complex derives from
ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by
ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the
ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif
in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a
functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG
levels in mice in the presence of ANGPTL3.
PMID- 28413162
TI - Whole-Genome Sequence of the Metastatic PC3 and LNCaP Human Prostate Cancer Cell
Lines.
AB - The bone metastasis-derived PC3 and the lymph node metastasis-derived LNCaP
prostate cancer cell lines are widely studied, having been described in thousands
of publications over the last four decades. Here, we report short-read whole
genome sequencing (WGS) and de novo assembly of PC3 (ATCC CRL-1435) and LNCaP
(clone FGC; ATCC CRL-1740) at ~70 * coverage. A known homozygous mutation in TP53
and homozygous loss of PTEN were robustly identified in the PC3 cell line,
whereas the LNCaP cell line exhibited a larger number of putative inactivating
somatic point and indel mutations (and in particular a loss of stop codon
events). This study also provides preliminary evidence that loss of one or both
copies of the tumor suppressor Capicua (CIC) contributes to primary tumor relapse
and metastatic progression, potentially offering a treatment target for
castration-resistant prostate cancer (CRPC). Our work provides a resource for
genetic, genomic, and biological studies employing two commonly-used prostate
cancer cell lines.
PMID- 28413164
TI - Resistance Economy and New Population Policy in Iran.
AB - .
PMID- 28413165
TI - Applying Multi-Theory Model (MTM) of Health Behavior Change to Predict Water
Consumption Instead of Sugar-Sweetened Beverages.
AB - BACKGROUND: A substantial proportion of college students to not drink enough
water and consume sugar-sweetened beverages (SSBs). Consumption of SSBs is
associated with weight gain, obesity, type 2 diabetes mellitus, dental carries,
and increased risk for cardiovascular disease. Hence, the purpose of this study
was to use the multi-theory model (MTM) in predicting initiation and sustenance
of plain water consumption instead of sugar-sweetened beverages among college
students. STUDY DESIGN: A cross-sectional study. METHODS: In this cross-sectional
study, a 37-item valid and reliable MTM-based survey was administered to college
students in 2016 via Qualtrics at a large public university in the Southeastern
United States. Overall, 410 students responded to the survey; of those, 174 were
eligible for the study and completed it. RESULTS: Stepwise multiple regression
analysis revealed that 61.8% of the variance in the initiation of drinking plain
water instead of SSBs was explained by behavioral confidence (P<0.001) and
changes in the physical environment (P<0.001). Further, 58.3% of the variance in
the sustenance of drinking plain water instead of SSBs was explained by emotional
transformation (P<0.001) and practice for change (P=0.001). CONCLUSIONS: Multi
theory model of health behavior change is a robust theory for predicting plain
water consumption instead of SSBs in college students. Interventions should be
developed based on this theory for this target population.
PMID- 28413166
TI - Health Literacy Scale and Causal Model of Childhood Overweight.
AB - BACKGROUND: WHO focuses on developing health literacy (HL) referring to cognitive
and social skills. Our objectives were to develop a scale for evaluating the HL
level of Thai childhood overweight, and develop a path model of health behavior
(HB) for preventing obesity. STUDY DESIGN: A cross-sectional study. METHODS: This
research used a mixed method. Overall, 2,000 school students were aged 9 to 14 yr
collected by stratified random sampling from all parts of Thailand in 2014. Data
were analyzed by CFA, LISREL. RESULTS: Reliability of HL and HB scale ranged 0.62
to 0.82 and factor loading ranged 0.33 to 0.80, the subjects had low level of HL
(60.0%) and fair level of HB (58.4%), and the path model of HB, could be
influenced by HL from three paths. Path 1 started from the health knowledge and
understanding that directly influenced the eating behavior (effect sized - beta
was 0.13, P<0.05. Path 2 the health knowledge and understanding that influenced
managing their health conditions, media literacy, and making appropriate health
related decision beta=0.07, 0.98, and 0.05, respectively. Path 3 the accessing
the information and services that influenced communicating for added skills,
media literacy, and making appropriate health-related decision beta=0.63, 0.93,
0.98, and 0.05. Finally, basic level of HL measured from health knowledge and
understanding and accessing the information and services that influenced HB
through interactive, and critical level beta= 0.76, 0.97, and 0.55, respectively.
CONCLUSIONS: HL Scale for Thai childhood overweight should be implemented as a
screening tool developing HL by the public policy for health promotion.
PMID- 28413167
TI - Impact of a New Law to Reduce the Legal Blood Alcohol Concentration Limit - A
Poisson Regression Analysis and Descriptive Approach.
AB - BACKGROUND: In Chile, a new law introduced in March 2012 lowered the blood
alcohol concentration (BAC) limit for impaired drivers from 0.1% to 0.08% and the
BAC limit for driving under the influence of alcohol from 0.05% to 0.03%, but its
effectiveness remains uncertain. The goal of this investigation was to evaluate
the effects of this enactment on road traffic injuries and fatalities in Chile.
STUDY DESIGN: A retrospective cohort study. METHODS: Data were analyzed using a
descriptive and a Generalized Linear Models approach, type of Poisson regression,
to analyze deaths and injuries in a series of additive Log-Linear Models
accounting for the effects of law implementation, month influence, a linear time
trend and population exposure. A review of national databases in Chile was
conducted from 2003 to 2014 to evaluate the monthly rates of traffic fatalities
and injuries associated to alcohol and in total. RESULTS: It was observed a
decrease by 28.1 percent in the monthly rate of traffic fatalities related to
alcohol as compared to before the law (P<0.001). Adding a linear time trend as a
predictor, the decrease was by 20.9 percent (P<0.001).There was a reduction in
the monthly rate of traffic injuries related to alcohol by 10.5 percent as
compared to before the law (P<0.001). Adding a linear time trend as a predictor,
the decrease was by 24.8 percent (P<0.001). CONCLUSIONS: Positive results
followed from this new 'zero-tolerance' law implemented in 2012 in Chile. Chile
experienced a significant reduction in alcohol-related traffic fatalities and
injuries, being a successful public health intervention.
PMID- 28413168
TI - Prevalence of HIV, HBV, and HCV and Related Risk Factors amongst Male Homeless
People in Lorestan Province, the West of Iran.
AB - BACKGROUND: Homeless people are at a higher risk of blood-born infectious
diseases. The aim of this study was to estimate the prevalence of HIV, HBV, HCV
and related risk factors among male homeless people. STUDY DESIGN: A cross
sectional study. METHODS: This study was conducted in Khorramabad City, western
Iran from January to June 2015. A pre-designed validated questionnaire was used
to collect the data on behavioral and other potential risk factors. Blood samples
were taken in order to diagnose HIV, hepatitis B and C infections. The prevalence
of HIV, hepatitis B, C and related risk factors was reported with a 95%
confidence interval (CI). RESULTS: The participants were 307 male homeless people
with a mean (+/-SD) age of 35.86 (+/-9.62) yr. The prevalence of HIV, HBs Ag, and
HCV Ab positive cases was 6.51% (95% CI: 4.23, 9.90), 0.98% (95% CI: 0.31, 3.00),
and 31.27% (26.31, 36.71), respectively. The prevalence of co-infections of HIV
and HCV Ab+ was 5.76% (95% CI: 1.34, 8.51). The most common recently used drugs
were heroin, methamphetamine, and opium with a prevalence of 44.30%, 41.04%, and
24.76%, correspondingly. CONCLUSIONS: According to this study, prevalence of HIV
and hepatitis C among homeless people was considerable. Abusing heroin,
methamphetamine, and industrial drugs was also significant. Considering the
association between drug abuse, HIV, and hepatitis C infections, planning for
effective control and preventive interventions is important in homeless people.
PMID- 28413170
TI - Selecting Strategies to Reduce High-Risk Unsafe Work Behaviors Using the Safety
Behavior Sampling Technique and Bayesian Network Analysis.
AB - BACKGROUND: High-risk unsafe behaviors (HRUBs) have been known as the main cause
of occupational accidents. Considering the financial and societal costs of
accidents and the limitations of available resources, there is an urgent need for
managing unsafe behaviors at workplaces. The aim of the present study was to find
strategies for decreasing the rate of HRUBs using an integrated approach of
safety behavior sampling technique and Bayesian networks analysis. STUDY DESIGN:
A cross-sectional study. METHODS: The Bayesian network was constructed using a
focus group approach. The required data was collected using the safety behavior
sampling, and the parameters of the network were estimated using Expectation
Maximization algorithm. Using sensitivity analysis and belief updating, it was
determined that which factors had the highest influences on unsafe behavior.
RESULTS: Based on BN analyses, safety training was the most important factor
influencing employees' behavior at the workplace. High quality safety training
courses can reduce the rate of HRUBs about 10%. Moreover, the rate of HRUBs
increased by decreasing the age of employees. The rate of HRUBs was higher in the
afternoon and last days of a week. CONCLUSIONS: Among the investigated variables,
training was the most important factor affecting safety behavior of employees. By
holding high quality safety training courses, companies would be able to reduce
the rate of HRUBs significantly.
PMID- 28413169
TI - Respiratory Effects of Simultaneous Exposure to Respirable Crystalline Silica
Dust, Formaldehyde, and Triethylamine of a Group of Foundry Workers.
AB - BACKGROUND: Foundry workers are occupationally exposed to hazardous substances
such as silica dusts and toxic gases. The aim of this study was to examine the
effects of simultaneous exposure to complex mixtures of silica dust,
formaldehyde, and triethylamine on lung function parameters. STUDY DESIGN: A
cross-sectional study. METHODS: This study was conducted on 55 male workers of
core making unit of a foundry plant (the case group) and 55 workers in a food
industry were enrolled as a control group in 2015. Workers were monitored for
personal exposure to crystalline silica respirable dust, according the NIOSH
method No.7602. The concentrations of formaldehyde and triethylamine were
measured using a PID instrument. Lung function tests were performed according to
the ERS/ATS standards. RESULTS: The mean concentrations of personal exposure to
silica dust, formaldehyde, and triethylamine in the core making workers were 0.23
mg/m3, 2.85 ppm, and 5.55 ppm and respective exposures of control subjects were
less than the LOD (limit of detection). There were significant associations
between exposure to silica dust and decreases in FVC (Forced vital capacity)
values (P<0.05). The findings showed a statistically significant synergistic
effect of silica dust and triethylamine on FVC values (P<0.05). CONCLUSIONS: The
mean exposure of all studied substances was higher than occupational exposure
limits. Synergistic effects of exposure to silica dust and triethylamine on some
lung function parameters were observed. Simultaneous exposure of foundry workers
to silica dust and triethylamine could impair lung function.
PMID- 28413171
TI - Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis
Of Breast Cancer Patients in Rafsanjan.
AB - BACKGROUND: Breast cancer is the most common cancer after lung cancer and the
second cause of death. In this study we compared Weibull and Lognormal Cure
Models with Cox regression on the survival of breast cancer. STUDY DESIGN: A
cohort study. METHODS: The current study retrospective cohort study was conducted
on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern
Iran from 2001 to 2015 suffering from breast cancer. We determined and analyzed
the effective survival causes by different models using STATA14. RESULTS:
According to AIC, log-normal model was more consistent than Weibull. In the
multivariable Lognormal model, the effective factors like smoking, second -hand
smoking, drinking herbal tea and the last breast-feeding period were included. In
addition, using Cox regression factors of significant were the disease grade,
size of tumor and its metastasis (p-value<0.05). As Rafsanjan is surrounded by
pistachio orchards and pesticides applied by farmers, people of this city are
exposed to agricultural pesticides and its harmful consequences. The effect of
the pesticide on breast cancer was studied and the results showed that the effect
of pesticides on breast cancer was not in agreement with the models used in this
study. CONCLUSIONS: Based on different methods for survival analysis, researchers
can decide how they can reach a better conclusion. This comparison indicates the
result of semi-parametric Cox method is closer to clinical experiences evidences.
PMID- 28413172
TI - The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth
factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats.
AB - To understand metformin's effects on fibroblast growth factors (FGFs) and
fibroblast growth factor receptor 1 (FGFR1), we investigated circulating
fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes
mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was
detected to explain the possible mechanisms. T2DM was induced by feeding rats
with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ,
30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow;
diabetic rats (DM) were fed on high-fat diet supplemented with or without
metformin (METF) for 12 weeks (500 mg.kg-1.d-1). Biochemical parameters were
detected at the end of 24th weeks. FGFR1 expression and protein kinase B (Akt)
phosphorylation in the pancreas and visceral adipose tissues were detected using
either Western blot (WB) or immunohistochemistry (IHC). Serum FGF19 and FGF21
were measured using enzyme-linked immune sorbent assay (ELISA). Metformin treated
DM rats showed improved glucose, lipid and bile acid metabolism. Besides,
significantly decreased FGF19 and increased FGF21 were observed in DM+METF rats.
DM rats showed significantly increased FGFR1 both in the pancreas and visceral
adipose tissues. While in DM+METF rats, FGFR1 was almost remained at a normal
level in the pancreas and increased in the visceral adipose tissue compared to
that in DM rats. Besides, metformin treatment restores Akt phosphorylation in
both tissues. The altered glucose and lipid profiles by metformin treatment may
be associated with the increased circulating FGF21 and tissue-specific
expressions of FGFR1.
PMID- 28413173
TI - 25-Hydroxyvitamin D serum level in Hashimoto's thyroiditis, but not Graves'
disease is relatively deficient.
AB - Vitamin D is a modulator of both the innate and adaptive immune system. As
vitamin D deficiency was a risk factor for some autoimmune diseases, we aimed to
evaluate the serum vitamin D levels in autoimmune thyroid diseases (AITD)
including Graves' disease (GD) and Hashimoto's thyroiditis (HT) and investigated
the association between serum vitamin D levels and AITD. 175 AITD patients
including 51 GD, 61 euthyroid HT (mild HT), 63 euthyroid HT patients with
hypothyroidism receiving hormone therapy (treated HT) were recruited from the
outpatient department. 51 controls were from the physical checkup center of the
hospital. 25-Hydroxyvitamin D levels, thyroid function, antithyroid antibodies,
IL-4, IL-17, and TNF-alpha were determined. Compared with the controls, treated
and mild HT patients had significantly lower 25(OH)D levels (45.77+/-3.48 vs.
83.49+/-6.24 nmol/L, p<0.001) and (55.25+/-3.88 vs. 83.49+/-6.24 nmol/L,
p<0.001), respectively. However, GD patients had similar 25(OH)D levels (81.77+/
5.60 vs. 83.49+/-6.24 nmol/L, p=0.808). Compared to 24.1% controls with prevalent
vitamin D deficiency, mild HT and treated HT patients were significantly
different (55.4%, p<0.001) and (70.3%, p<0.001), respectively; no difference was
seen in the GD patients (22.9%, p=0.797). Serum 25(OH)D levels were not
associated with thyroid function, antithyroid antibodies, and serum cytokines IL
4, IL-17, and TNF-alpha in patients with AITD. We observed relatively low vitamin
D level in mild and treated HT patients, while GD patients had similar 25(OH)D
levels to those of healthy individuals. Further studies are imperative to explore
the complex etiology of vitamin D deficiency in AITD.
PMID- 28413174
TI - An outbreak of duck hepatitis A virus type 1 infection in Japan.
AB - In June 2015, a highly fatal and acute disease broke out in a duckling farm in
Hyogo Prefecture, Japan. The birds exhibited poor growth, reduced movement, lying
in a dorsal recumbent position, depression, lethargy, ataxia and opisthotonus,
with a high mortality rate of approximately 76%. By performing a reverse
transcription-polymerase chain reaction (RT-PCR) using primers specific for duck
hepatitis A virus type 1 (DHAV-1), we obtained the PCR products of a predicted
size. The nucleotide sequences of the PCR products showed a >96% identity with
that of the DHAV-1, HB02 strain, which was isolated in China. To our knowledge,
this is the first time that the DHAV-1 virus has been isolated since its outbreak
in Japan in 1963.
PMID- 28413175
TI - Prenatal postcranial development in two species of sympatric Japanese wood mice
(Apodemus argenteus and A. speciosus): a comparison of arboreal versus
terrestrial congeners.
AB - Habitats of two closely related Japanese field mice, Apodemus argenteus and A.
speciosus, broadly overlap in many Japanese forests. A. argenteus being more
arboreal and A. speciosus being more terrestrial, it is thought that such
ecological segregation allows their sympatric distribution. Comparing these two
congeners, whether ecological difference is reflected in postcranial development
was examined. Although overall ossification sequences were virtually identical,
development of the caudal vertebrae was remarkably earlier in A. argenteus. One
of the clearest morphological differences between the two species is the relative
length of the tail, which is arguably related to the degree of arboreality. I
suggest that accelerated ossification of the caudal vertebrae found in A.
argenteus is related to its elongation of the tail.
PMID- 28413176
TI - Investigating right ovary degeneration in chick embryos by transcriptome
sequencing.
AB - In asymmetric chick gonads, the left and right female gonads undergo distinct
programs during development, generating a functional ovary on the left side only.
Despite some progress being made in recent years, the mechanisms of molecular
regulation remain incompletely understood, and little genomic information is
available regarding the degeneration of the right ovary in the chick embryo
testis. In this study, we performed transcriptome sequencing to investigate
differentially expressed genes in the left and right ovaries and gene functions
at two critical time points; embryonic days 6 (E6) and 10 (E10). Using high
throughput RNA-sequencing technologies, 539 and 1046 genes were identified as
being significantly differentially expressed between 6R-VS-6L and 10R-VS-10L.
Gene ontology analysis of the differentially expressed genes revealed enrichment
in functional pathways. Among these, candidate genes associated with degeneration
of the right ovary in the chick embryo were identified. Identification of a
pathway involved in ovarian degeneration provides an important resource for the
further study of its molecular mechanisms and functions.
PMID- 28413177
TI - Exercise Transcutaneous Oximetry of the Buttocks - External Validation With
Computed Tomography Angiography.
AB - BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is a non-invasive test
for exercise-induced buttock ischemia. Prior study defined Ex-tcPO2
normal/abnormal cut-offs against arteriography but no external validation was
available. The aims of this study were therefore to (1) determine the diagnostic
performance of Ex-tcPO2 against CTA; (2) determine the cut-off point for
detection of stenosis >75% in arteries toward the hypogastric circulation; and
(3) determine the effect of chest profile classification on the diagnostic
performance of Ex-tcPO2.Methods and Results:A total of 207 patients referred for
Ex-tcPO2 were analyzed. DROP during Ex-tcPO2 was compared with the CTA results.
Chest-tcPO2 changes were automatically classified into pre-defined profiles
representing normal or abnormal responses. Using DROP <-15 mmHg as a cut-off, Ex
tcPO2 had 80.2% sensitivity, 72.3% specificity, 43.1% PPV, 93.3% NPV and 73.9%
accuracy, to detect 1 stenosis >75% in arteries toward the hypogastric
circulation. Optimal DROP to detect stenosis was: -15 mmHg. The overall
diagnostic performance of Ex-tcPO2 was independent of chest profile
classification. CONCLUSIONS: Ex-tcPO2 has satisfactory diagnostic performance to
detect arterial stenoses towards the hypogastric circulation. Abnormal chest
tcPO2 profile does not impair the overall diagnostic performance of the test.
PMID- 28413178
TI - Synthesized Abeta42 Caused Intracellular Oxidative Damage, Leading to Cell Death,
via Lysosome Rupture.
AB - Neuronal cellular accumulation of amyloid beta peptide (Abeta) has been
implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular
accumulation of Abeta42, a toxic form of Abeta, was observed as an early event in
AD patients. However, its contribution and the cellular mechanism of cell death
remained unclear. We herein revealed the mechanism by which Abeta42 incorporated
into cells leads to cell death by using chemically synthesized Abeta42 variants.
The Abeta42 variant Abeta42 (E22P) which has an increased tendency to
oligomerize, accumulated in lysosomes at an earlier stage than wild-type Abeta42,
leading to higher ROS production and lysosomal membrane oxidation, and resulting
in cell death. On the other hand, Abeta42 (E22V), which is incapable of
oligomerization, did not accumulate in cells or affect the cell viability.
Moreover, intracellular localization of EGFP-Galectin-3, a beta-galactoside
binding lectin, showed that accumulation of oligomerized Abeta42 in lysosomes
caused lysosomal membrane permeabilization (LMP). Overexpression of lysosome
localized LAMP1-fused peroxiredoxin 1 and treatment with U18866A, an inhibitor of
cholesterol export from lysosomes that causes an increase in lysosomal membrane
stability, attenuated Abeta42-mediated LMP and cell death. Our findings show that
lysosomal ROS generation by toxic conformer of Abeta led to cell death via LMP,
and suggest that these events are potential targets for AD prevention.Key words:
Amyloid-beta (Abeta), Cell death, Lysosome, Lysosomal membrane permeabilization,
Reactive oxygen species (ROS).
PMID- 28413179
TI - Cyclic thrombocytopenia synchronizing with the menstrual cycle showing periodic
phases of thrombocytopenia and rebound thrombocytosis.
AB - A 37-year-old woman was admitted to our hospital for purpura involving the
extremities and thrombocytopenia. Prednisolone (PSL) was administered based on a
diagnosis of idiopathic thrombocytopenic purpura (ITP), but was not effective for
maintaining her platelet count within the normal range, which showed cyclic
fluctuation corresponding to the menstrual cycle. Therefore, we discontinued PSL,
and cyclic thrombocytopenia (CTP) was diagnosed. CTP is a rare disease which is
usually treated as ITP but with no response. Although the exact cause of CTP is
uncertain, in our case, a hormonal mechanism may be responsible for fluctuating
platelet count.
PMID- 28413180
TI - Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose
Lowering.
AB - AIM: Myriad biological effects of leptin may lead to broad therapeutic
applications for various metabolic diseases, including diabetes and its
complications; however, in contrast to its anorexic effect, the molecular
mechanisms underlying adipopenic and glucose-lowering effects of leptin have not
been fully understood. Here we aim to clarify the role of hormone-sensitive
lipase (HSL) in leptin's action. METHODS: Wild-type (WT) and HSL-deficient
(HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus
mediated overexpression of leptin and continuous subcutaneous infusion of leptin
by osmotic pumps. The amount of food intake, body weights, organ weights, and
parameters of glucose and lipid metabolism were measured. RESULTS:
Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the
other hand, leptin-mediated fat loss and glucose-lowering were significantly
blunted in the absence of HSL when leptin was overexpressed by recombinant
adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering
effects of leptin were milder due to lower levels of hyperleptinemia; although
the difference between WT and HSLKO mice did not reach statistical significance,
HSLKO mice had a tendency to retain more fat than WT mice in the face of
hyperleptinemia. CONCLUSIONS: We clarify for the first time the role of HSL in
leptin's effect using a genetic model: leptin-promoted fat loss and glucose
lowering are at least in part mediated via HSL-mediated lipolysis. Further
studies to define the pathophysiological role of adipocyte lipases in leptin
action may lead to a new therapeutic approach to circumvent leptin resistance.
PMID- 28413181
TI - Review of Past Reports and Current Concepts of Surgical Management for
Craniosynostosis.
AB - The purposes of surgery for craniosynostosis are to release increased
intracranial pressure and to normalize cranial shape. The procedure was developed
from a simple strip craniectomy in practice which ranged from the removal of the
fused suture before the 1960s to total calvarial remodeling after 1970s and later
methods of the 1990s, such as distraction and its modifications. According to its
history, craniofacial surgeons might be changing their procedures with more
effective, than less invasive ways. Since the late 1990s, when the distraction
was applied to the craniofacial surgery, the gradual expansion, in particular of
the anterior cranium, common in Japan, has long been controversial until the
Caucasians accepted its use for the posterior cranium. Currently, the method may
revert to the old procedure because a more sophisticated and better morphological
result can be obtained depending on the types of deformity, even if a little more
invasive maneuver is required. In other words, if treatment can be performed in
optimal time, the procedures that were developed in the last half a century
should be altered to each condition.
PMID- 28413182
TI - Introduction to the concept of signal toxicity.
AB - Silent Spring by Rachel Carson (1962) established a role for environmental
chemicals in cancer and Our Stolen Future by Theo Colbone, Dianne Dumanoski and
John Peterson Myers (1996) coined the concept of "Endocrine Disrupting Chemicals
(EDCs)" with its mechanistic plausibility for all the living organisms. For basic
biologists, seeing a non-monotonic dose-response curve was a matter of course. In
contrast, for the toxicologists at that time, the dose-response curves should be
monotonic. It took some time for toxicologists to accept the plausibility that
animals and humans are subject to the effects of EDCs act in a way that is
explained by the new paradigm of receptor-mediated toxicity or in other words
"signal toxicity." In classical toxicology, a toxic substance reaches a cellular
target and induces malfunction. The target molecules are proteins including
enzymes, lipid membranes, DNA, and other components of the cell which are damaged
by the toxic substances. On the other hand, in the case of signal toxicity, a
chemical binds to a specific receptor - after that, the chemical itself is not
important. The signal from the receptor initiates a cascade of molecular events
that leads to various changes in the cells and organs. When the signal is
abnormal for a cell or an organ in terms of quality, intensity and timing, then
the signal will induce adverse effects to the target. An extreme example of
signal toxicity is the 1981 Nobel Prize in Physiology or Medicine work by Drs.
Hubel and Wiesel. They blocked the signal of sharp images from the retina to the
brain and found that the visual cortex needed this signal at the correct time for
its proper development. In humans, such signal disruption is well known to induce
"form-deprivation amblyopia" in infants. The concept of signal toxicity widens
the range of systems vulnerable to EDCs and facilitates the understanding of
their biological characteristics. For example, compared with intrinsic ligands,
xenobiotic chemicals usually act as weak agonists and/or weak antagonists of
receptor systems; the dose-response characteristics and the dose range will
depend on the signaling system of concern. If the signal is used for
organogenesis and functional maturation, there would be a critical period in the
development during which the disturbance of such signals may cause irreversible
changes. Since recepter-based signaling mechanisms are usually an amplification
systems, it is hard to set a threshold in its dose response, and the outcome of
signal toxicity is often stochastic at low doses. This review attempts to explain
the benefits of incorporating the concept of signal toxicology for widening the
range of toxicology for the better protection of human and environmental health
in modern civilized life, where chemicals are designed to be less toxic in terms
of traditional toxicity but not yet in "signal toxicity."
PMID- 28413183
TI - A SLC24A2 Gene Variant Uncovered in Pancreatic Ductal Adenocarcinoma by Whole
Exome Sequencing.
AB - Pancreatic ductal adenocarcinoma (PDAC) presents as an aggressive malignancy
caused by environmental and genetic factors. In order to identify causal genes
for PDAC, we performed whole exome sequencing (WES) to detect gene mutations in
seven pairs of PDAC tissue and adjacent non-tumor tissue samples. Finally, we
found a new nonsynonymous single nucleotide variant (nsSNV) in solute carrier 24
family member 2 (SLC24A2) gene resulting in the substitution of native glutamic
acid (E) into aspartic acid (D) at position of 287 amino acid (E287D) in SLC24A2
protein, and confirmed this variant by Sanger gene sequencing. SLC24A2 is a
potassium-dependent sodium-calcium exchanger and can transport metal ion across
cell membrane. Multiple in silico variants' effects analyses methods including
SIFT, PolyPhen, PROVEAN, and PANTHER demonstrated this variant had probably
damaging effects, which was consistent with the results obtained from Mutation
Taster software analysis with a probability of 0.99999997 to be "disease
causing." The three dimension (3D) structure analysis results suggested this
variant had little effects on the solubility and hydrophobicity of the protein;
but it could decrease the protein stability by increasing the total protein
structure energy (-8874.33 kJ/mol for the mutant and -8963.54 kJ/mol for the
native) and by causing the mutant protein decreasing three stabilizing residues.
Less stability of the mutant 287D protein than the native E287 protein was also
supported by I-Mutant and Western-blotting analysis results. Overall, a new
mutation in SLC24A2 gene was identified to decrease the stability of SLC24A2,
which may have potential clinical usages.
PMID- 28413184
TI - Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation Not
Receiving Oral Anticoagulants - Korean Nationwide Population-Based Study.
AB - BACKGROUND: Atrial fibrillation, the most common cardiac arrhythmia, is
associated with an elevated thromboembolic risk, including ischemic stroke.
Guidelines recommend the stratification of individual stroke risk and tailored
antithrombotic therapy. This study investigated the demographics, comorbidities,
and prognosis of non-valvular AF (NVAF) in Korean patients.Methods and Results:We
extracted data on 10,846 patients with newly diagnosed NVAF who were naive to
oral anticoagulants from the National Health Insurance Service-National Sample
Cohort. CHADS2and CHA2DS2-VASc scores were calculated for each subject using
claims data. The study endpoints were ischemic stroke, thromboembolism, and
mortality. Mean age was 63.7 years, and 46.8% of the patients were women. Women
were older and had higher CHADS2and CHA2DS2-VASc scores. During 30,138 person
years of follow-up, ischemic stroke occurred at a rate of 2.95/100 person-years.
CHADS2and CHA2DS2-VASc scores showed good performance in risk prediction. CHA2DS2
VASc score performed better at discriminating stroke risk in patients with low
risk profiles. The presence of female sex and vascular disease added little
improvement in risk prediction. CONCLUSIONS: Korean NVAF patients had high risk
of stroke and mortality, and had multiple comorbidities. While both CHADS2and
CHA2DS2-VASc schema had good performance in risk prediction, CHA2DS2-VASc score
was superior in identifying truly low-risk patients. Given that Asian ethnicity
is associated with bleeding events, individualized accurate risk prediction is
necessary to improve patient outcomes.
PMID- 28413185
TI - Comparison of the Long-Term Outcomes of Mechanical and Bioprosthetic Aortic
Valves - A Propensity Score Analysis.
AB - BACKGROUND: The aim of this study was to assess the long-term outcomes of aortic
valve replacement (AVR) with either mechanical or bioprosthetic valves according
to age at operation.Methods and Results:A total of 1,002 patients (527 mechanical
valves and 475 bioprosthetic valves) undergoing first-time AVR were categorized
according to age at operation: group Y, age <60 years; group M, age 60-69 years;
and group O, age >=70 years). Outcomes were compared on propensity score analysis
(adjusted for 28 variables). Hazard ratio (HR) was calculated using the Cox
regression model with adjustment for propensity score with bioprosthetic valve as
a reference (HR=1). There were no significant differences in overall mortality
between mechanical and bioprosthetic valves for all age groups. Valve-related
mortality was significantly higher for mechanical valves in group O (HR, 2.53;
P=0.02). Reoperation rate was significantly lower for mechanical valves in group
Y (HR, 0.16; P<0.01) and group M (no events for mechanical valves). Although the
rate of thromboembolic events was higher in mechanical valves in group Y (no
events for tissue valves) and group M (HR, 9.05; P=0.03), there were no
significant differences in bleeding events between all age groups. CONCLUSIONS:
The type of prosthetic valve used in AVR does not significantly influence overall
mortality.
PMID- 28413187
TI - Noninvasive Fractional Flow Reserve Derived From Coronary Computed Tomography
Angiography - Is This Just Another New Diagnostic Test or the Long-Awaited Game
Changer?
AB - Despite the clinical importance of ischemia evaluation, obtaining fractional flow
reserve (FFR) value has, heretofore, only been available during invasive cardiac
catheterization. Although there is a clear linkage between morphology and
physiology, a significant gap still exists. FFR derived from coronary computed
tomography angiography (FFRCT) is a novel method of quantifying the hemodynamic
significance of coronary artery stenoses by translating morphological information
into hemodynamic data. Improved diagnostic performance of FFRCThas been
repeatedly demonstrated in comparison with coronary computed tomography
angiography alone with an invasive FFR reference standard. More recently, the
potential benefit of this technology to safely defer non-indicated
catheterizations and reduce healthcare costs has been established and indicates
this technology may improve the management of patients with coronary artery
disease. In this review, we summarize the scientific basis of FFRCTand evidence
from clinical trials, provide illustrative examples of clinical applications,
discuss potential limitations, and outline avenues for future research.
PMID- 28413186
TI - The characterization of a full-thickness excision open foot wound model in n5
streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer
in terms of reduced blood circulation, higher C-reactive protein, elevated
inflammation, and reduced cell proliferation.
AB - Delayed foot wound healing is a major complication attributed to hyperglycemia in
type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot
ulcers. There are at least two types of DM wound models used in rodents to study
delayed wound healing. However, clinically relevant animal models are not common.
Most models use type 1 DM rodents or wounds created on the back rather than on
the foot. An open full-thickness excision wound on the footpad of type 2 DM rats
is more clinically relevant, but such a model has not yet been characterized
systematically. The objective of this study was to investigate and characterize
how DM affected a full-thickness excision open foot wound in n5-streptozotocin
(n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation,
reduced blood circulation, and cell proliferation due to hyperglycemia could
delay the wound healing of DM rats. The wounds of DM rats were compared with
those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing
process of the DM rats was significantly delayed compared with that of the Ctrl
rats. The DM rats also had higher C-reactive protein (CRP) and lower blood
circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This
confirmed that elevated inflammation and reduced blood flow and cell
proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open
foot wound animal model provides a good approach to study the process of delayed
wound healing.
PMID- 28413188
TI - Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration
and Risk of Cardiovascular Events - Systematic Review and Meta-Analysis of
Prospective Studies.
AB - BACKGROUND: Previous studies have not found a consistent association between
circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) and the risk of
cardiovascular events. The aim of this meta-analysis was to evaluate this
association in prospective studies.Methods and Results:A systematic search of
prospective studies published through October 2016 was carried out in order to
identify studies that met pre-specified inclusion criteria. After independent
data extraction, summary relative risks were calculated using random-effects
models. On meta-analysis of 6 cohort and 1 nested case-control study, circulating
PCSK9 concentration as a continuous variable was not significantly associated
with the risk of cardiovascular events (overall RR, 1.12; 95% CI: 0.98-1.29;
P=0.09), with significant heterogeneity (I2=55.1%, Pheterogeneity=0.038). The
highest but not middle categories of circulating PCSK9 was significantly
associated with the risk of cardiovascular events. On subgroup analysis of study
design, mean age at baseline, sample size, follow-up time, and pre-existing
disease, there was no significant association between PCSK9 and cardiovascular
events. Sensitivity analysis with various exclusion and inclusion criteria did
not materially change the results. CONCLUSIONS: Circulating PCSK9 concentration
as a continuous variable was not significantly associated with the risk of
cardiovascular events. More well-designed studies are needed to clarify the role
of PCSK9 in cardiovascular risk.
PMID- 28413189
TI - Heart Transplantation in Asia.
AB - Heart transplantation (HTx) is the effective way to improve quality of life as
well as survival in terminal heart failure (HF) patients. Since the first heart
transplant in 1968 in Japan and in earnest in 1987 at Taiwan, HTx has been
continuously increasing in Asia. Although the current percentage of heart
transplants from Asia comprises only 5.7% of cases in the International Society
of Heart and Lung Transplantation (ISHLT) registry, the values were under
reported and soon will be greatly increased. HTx in Asia shows comparable with or
even better results compared with ISHLT registry data. Several endemic
infections, including type B hepatitis, tuberculosis, and cytomegalovirus, are
unique aspects of HTx in Asia, and need special attention in transplant care.
Although cardiac allograft vasculopathy (CAV) is considered as a leading cause of
death after HTx globally, multiple observations suggest less prevalence and
benign nature of CAV among Asian populations. Although there are many obstacles
such as religion, social taboo or legal process, Asian countries will keep
overcoming obstacles and broaden the field of HTx.
PMID- 28413190
TI - Virgin Olive Oil Enriched with Lutein-Zeaxanthin from Spinacia oleracea.
AB - The aim of this work consists of developing a technological process for
elaborating a virgin olive oil enriched in lutein-zeaxanthin extracted from
spinach, studying different parameters like temperature, time of extraction and
different ratios (spinach-oil). It was observed that the amount of carotenoids
extracted increased up to a maximum after 24 hours and decreased as the
maceration time progressed up to 60 hours, resulting of biological degradation.
It was also observed that as more spinach we added, as more lutein-zeaxanthin in
the enriched virgin olive oil was obtained. The best results were obtained after
24 hours by using a 75:25 ratio at 30 degrees C. Values of oxidative stability
decreased drastically, as well as other parameters such as acidity; peroxides
index and Ks were modified when the enriched virgin olive oil was subjected to 45
degrees C for 24 hours of maceration. Thus, the present procedure constitutes a
way to achieve an increase in the daily intake of beneficial compounds.
PMID- 28413191
TI - Length-scale Specific Crystalline Structural Changes Induced by Molecular
Randomization of Pequi Oil.
AB - Pequi fruit (Caryocar brasiliense Camb) is considered important since its pulp
has a high content of oil and carotenoids. The oil's triacylglycerols (TAGs)
contain mainly oleic (~57%) and palmitic (~36%) fatty acids, distributed
primarily among POO, POP/PPO, and OOO TAGs. It displays a tendency to fractionate
upon storage and has a relatively low melting temperature (SFC of 4% at 25
degrees C). Pequi oil was modified through chemical interesterification, which
increased the PPP content to ~6%. This caused a flattening in the SFC-temperature
profile, raising the end of melt temperature significantly (SFC of 4% at 39
degrees C). The interesterified oil does not fractionate and is thermally stable
up to 40 degrees C, with an SFC-temperature profile resembling that of roll-in
shortening (SFC of 31% at 16 degrees C) despite containing high amounts of oleic
acid. Crystallization and melting behavior changed. Crystal packing became more
disorganized as evidenced by a significant decrease in crystalline domain size in
the [001] direction from 42.3 nm to 32.1 nm. Polymorphism remained of the
triclinic (beta) subcell type but polytypism changed from the 3L to the 2L type.
Polarized light microscopy demonstrated that interesterification dramatically
decreased crystal size, consistent with a higher rate of nucleation in the
material. Moreover, the dramatic improvement in physical stability and
functionality was not accompanied by a significant decrease in total carotenoid
content (~390 mg/kg).
PMID- 28413192
TI - Secondary Structural Changes of Intact and Disulfide Bridges-Cleaved Human Serum
Albumins in Thermal Denaturation up to 130 degrees C - Additive Effects of Sodium
Dodecyl Sulfate on the Changes.
AB - The secondary structural changes of human serum albumin with the intact 17
disulfide bridges (HSA) and the disulfide bridges-cleaved human serum albumin
(RCM-HSA) in thermal denaturation were examined. Most of the helical structures
of HSA, whose original helicity was 66%, were sharply disrupted between 50 and
100 degrees C. However, 14% helicity remained even at 130 degrees C. The
temperature dependence of the degree of disrupted helical structures of HSA was
discussed in connection with questions about a general protein denaturation
model. When HSA lost the disulfide bridges, about two-thirds of the original
helices were disrupted. Although the helices of RCM-HSA remaining after the
cleavage of the disulfide bridges were relatively resistant against the heat
treatment, the helicity changed from 22% at 25 degrees C to 14% at 130C. The
helicity of RCM-HSA at 130 degrees C agreed with the helicity of HSA at the same
temperature, indicating that the same helical moieties of the polypeptides
remained unaffected at this high temperature. The additive effects of sodium
dodecyl sulfate (SDS) on the structural changes of HSA and RCM-HSA in thermal
denaturation were also examined. A slight amount of SDS protected the helical
structures of HSA from thermal denaturation below 80 degrees C. Upon cooling to
25 degrees C after heat treatment at temperatures below 70 degrees C with the
coexistence of SDS of low concentrations, the helical structures of HSA were
reformed to the original level at 25 degrees C before heating. A similar tendency
was also observed after heat treatment at 80 degrees C. In contrast, the helical
structures of the RCM-HSA complexes with SDS are completely recovered upon
cooling to 25 degrees C even after heat treatment up to 100 degrees C. Similar
investigations were also carried out on bovine serum albumins which had the
intact 17 disulfide bridges and lost all of the bridges.
PMID- 28413193
TI - Effect of Dietary Purified Xanthohumol from Hop (Humulus lupulus L.) Pomace on
Adipose Tissue Mass, Fasting Blood Glucose Level, and Lipid Metabolism in KK-Ay
Mice.
AB - We previously showed that xanthohumol-rich hop extract (XRHE, ~18% xanthohumol)
exerts anti-obesity effects in rats fed a high-fat diet through regulation of
fatty acid metabolism. In this study, we examined the effects of dietary purified
xanthohumol from XRHE (PX, ~91.9% xanthohumol) in KK-Ay mice in order to
understand the anti-obesity effects of xanthohumol alone because XRHE contains
82% unknown compounds. Dietary consumption of PX significantly inhibited an
increase in the visceral fat weight of mice compared to those fed control diet
without PX. Plasma leptin level was significantly lower in the PX-fed group than
in the control group. Dietary PX lowered hepatic fatty acid synthesis by down
regulation of SREBP1c mRNA expression in the liver. On the other hand, fatty acid
beta-oxidation in the liver was promoted by dietary PX through the up-regulation
of PPARalpha mRNA expression. Moreover, the fecal levels of fatty acids and
carbohydrates increased by dietary PX. PX inhibited lipase or alpha-amylase
activity in vitro. Thus, we found that PX may exert anti-obesity effects through
the regulation of lipid metabolism and inhibition of intestinal fat and
carbohydrate absorption, and that xanthohumol alone may exert anti-obesity
effects.
PMID- 28413195
TI - Purinergic signaling in microglia in the pathogenesis of neuropathic pain.
AB - Nerve injury often causes debilitating chronic pain, referred to as neuropathic
pain, which is refractory to currently available analgesics including morphine.
Many reports indicate that activated spinal microglia evoke neuropathic pain. The
P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in
spinal microglia after nerve injury by several factors, including CC chemokine
receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord,
interferon regulatory factor 8 (IRF8) and IRF5. Inhibition of P2X4R function
suppresses neuropathic pain, indicating that microglial P2X4R play a key role in
evoking neuropathic pain.
PMID- 28413194
TI - Dual role of cellular prion protein in normal host and Alzheimer's disease.
AB - Using PrPC-knockout cell lines, it has been shown that the inhibition of
apoptosis through STI1 is mediated by PrPC-dependent SOD activation. Antioxidant
PrPC may contribute to suppression of inflammasome activation. PrPC is
functionally involved in copper metabolism, signal transduction, neuroprotection,
and cell maturation. Recently several reports have shown that PrPC participates
in trans-membrane signaling processes associated with hematopoietic stem cell
replication and neuronal differentiation. In another role, PrPC also tends to
function as a neurotoxic protein. Abeta oligomer, which is associated with
neurodegeneration in Alzheimer's disease (AD), has also been reported to act as a
ligand of PrPC. However, the physiological role of PrPC as an Abeta42-binding
protein is not clear. Actually, PrPC is critical in Abeta42-mediated autophagy in
neurons. PrPC shows a beneficial role in lipid rafts to promote autophagy.
Further search for PrPC-interaction molecules using Prnp-/- mice and various
types of Prnp-/- cell lines under various conditions may elucidate other
important PrPC important functions.
PMID- 28413196
TI - The molecular cues regulating immune cell trafficking.
AB - Lymphocyte recirculation between the blood and the lymphoid/non-lymphoid tissues
is an essential homeostatic mechanism that regulates humoral and cellular immune
responses in vivo. This system promotes the encounter of naive T and B cells with
their specific cognate antigen presented by dendritic cells, and with the
regulatory cells with which they need to interact to initiate, maintain, and
terminate immune responses. The constitutive lymphocyte trafficking is mediated
by particular types of blood vessels, including the high endothelial venules
(HEVs) in lymph nodes and Peyer's patches, and the flat-walled venules in non
lymphoid tissues including the skin. The lymphocyte migration across HEVs
involves tethering/rolling, arrest/firm adhesion/intraluminal crawling, and
transendothelial migration. On the other hand, relatively little is known about
how lymphocytes and other types of cells migrate across the venules of non
lymphoid tissues. Here we summarize recent findings about the molecular
mechanisms that govern immune cell trafficking, including the roles of chemokines
and lysophospholipids in regulating immune cell motility and endothelial
permeability.
PMID- 28413198
TI - Engineering the lodging resistance mechanism of post-Green Revolution rice to
meet future demands.
AB - Traditional breeding for high-yielding rice has been dependent on the widespread
cultivation of gibberellin (GA)-deficient semi-dwarf varieties. Dwarfism lowers
the "center of gravity" of the plant body, which increases resistance against
lodging and enables plants to support high grain yield. Although this approach
was successful in latter half of the 20th century in rice and wheat breeding,
this may no longer be enough to sustain rice with even higher yields. This is
because relying solely on the semi-dwarf trait is subject to certain limitations,
making it necessary to use other important traits to reinforce it. In this
review, we present an alternative approach to increase lodging resistance by
improving the quality of the culm by identifying genes related to culm quality
and introducing these genes into high-yielding rice cultivars through molecular
breeding technique.
PMID- 28413197
TI - Structure and function of Helicobacter pylori CagA, the first-identified
bacterial protein involved in human cancer.
AB - Chronic infection with Helicobacter pylori cagA-positive strains is the strongest
risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered
into gastric epithelial cells via bacterial type IV secretion, where it undergoes
tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered
CagA then acts as a non-physiological scaffold/hub protein by interacting with
multiple host signaling molecules, most notably the pro-oncogenic phosphatase
SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine
phosphorylation-dependent and -independent manners. CagA-mediated manipulation of
intracellular signaling promotes neoplastic transformation of gastric epithelial
cells. Transgenic expression of CagA in experimental animals has confirmed the
oncogenic potential of the bacterial protein. Structural polymorphism of CagA
influences its scaffold function, which may underlie the geographic difference in
the incidence of gastric cancer. Since CagA is no longer required for the
maintenance of established gastric cancer cells, studying the role of CagA during
neoplastic transformation will provide an excellent opportunity to understand
molecular processes underlying "Hit-and-Run" carcinogenesis.
PMID- 28413199
TI - Rapid and coordinated processing of global motion images by local clusters of
retinal ganglion cells.
AB - Even when the body is stationary, the whole retinal image is always in motion by
fixational eye movements and saccades that move the eye between fixation points.
Accumulating evidence indicates that the brain is equipped with specific
mechanisms for compensating for the global motion induced by these eye movements.
However, it is not yet fully understood how the retina processes global motion
images during eye movements. Here we show that global motion images evoke novel
coordinated firing in retinal ganglion cells (GCs). We simultaneously recorded
the firing of GCs in the goldfish isolated retina using a multi-electrode array,
and classified each GC based on the temporal profile of its receptive field (RF).
A moving target that accompanied the global motion (simulating a saccade
following a period of fixational eye movements) modulated the RF properties and
evoked synchronized and correlated firing among local clusters of the specific
GCs. Our findings provide a novel concept for retinal information processing
during eye movements.
PMID- 28413200
TI - The oral microbiome community variations associated with normal, potentially
malignant disorders and malignant lesions of the oral cavity.
AB - The human oral microbiome has been known to show strong association with various
oral diseases including oral cancer. This study attempts to characterize the
community variations between normal, oral potentially malignant disorders (OPMD)
and cancer associated microbiota using 16S rDNA sequencing. Swab samples were
collected from three groups (normal, OPMD and oral cancer) with nine subjects
from each group. Bacteria genomic DNA was isolated in which full length 16S rDNA
were amplified and used for cloned library sequencing. 16S rDNA sequences were
processed and analysed with MOTHUR. A core oral microbiome was identified
consisting of Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes and
Actinobacteria at the phylum level while Streptococcus, Veillonella, Gemella,
Granulicatella, Neisseria, Haemophilus, Selenomonas, Fusobacterium, Leptotrichia,
Prevotella, Porphyromonas and Lachnoanaerobaculum were detected at the genus
level. Firmicutes and Streptococcus were the predominant phylum and genus
respectively. Potential oral microbiome memberships unique to normal, OPMD and
oral cancer oral cavities were also identified. Analysis of Molecular Variance
(AMOVA) showed a significant difference between the normal and the cancer
associated oral microbiota but not between the OPMD and the other two groups.
However, 2D NMDS showed an overlapping of the OPMD associated oral microbiome
between the normal and cancer groups. These findings indicated that oral microbes
could be potential biomarkers to distinguish between normal, OPMD and cancer
subjects.
PMID- 28413201
TI - Detection of alpha-thalassaemia in neonates on cord blood and dried blood spot
samples by capillary electrophoresis.
AB - INTRODUCTION: Haemoglobin Bart's (Hb Bart's) level is associated with alpha
thalassaemia traits in neonates, enabling early diagnosis of alpha-thalassaemia.
The study aimed to detect and quantify the Hb Bart's using Cord Blood (CB) and CE
Neonat Fast Hb (NF) progammes on fresh and dried blood spot (DBS) specimen
respectively by capillary electrophoresis (CE). METHODS: Capillarys Hemoglobin
(E) Kit (for CB) and Capillarys Neonat Hb Kit (for NF) were used to detect and
quantify Hb Bart's by CE in fresh cord blood and dried blood spot (DBS) specimens
respectively. High performance liquid chromatography (HPLC) using the beta-Thal
Short Programme was also performed concurrently with CE analysis. Confirmation
was obtained by multiplex ARMS Gap PCR. RESULTS: This study was performed on 600
neonates. 32/600 (5.3%) samples showed presence of Hb Bart's peak using the NF
programme while 33/600 (5.5%) were positive with CB programme and HPLC methods.
The range of Hb Bart's using NF programme and CB programme were (0.5-4.1%) and
(0.5-7.1%), respectively. Molecular analysis confirmed all positive samples
possessed alpha-thalassaemia genetic mutations, with 23/33 cases being
alphaalpha/--SEA, four -alpha3.7/-alpha3.7, two alphaalpha/-alpha3.7 and three
alphaalpha/alphaalphaCS. Fifty Hb Bart's negative samples were randomly tested
for alpha-genotypes, three were also found to be positive for alpha-globin gene
mutations. Thus, resulting in sensitivity of 91.7% and 88.9% and specificity of
100% for the Capillarys Cord Blood programme and Capillarys Neonat Fast programme
respectively. CONCLUSION: Both CE programmes using fresh or dried cord blood were
useful as a screening tool for alpha-thalassaemia in newborns. All methods show
the same specificity (100%) with variable, but acceptable sensitivities in the
detection of Hb Bart.
PMID- 28413202
TI - Conventional versus molecular detection of Chlamydia trachomatis and Neisseria
gonorrhoeae among males in a sexually transmitted infections clinic.
AB - BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae are important
bacterial pathogens of sexually transmitted infections (STIs) worldwide. This
study sought to compare the analytical sensitivity and specificity of
conventional methods against a rapid molecular method in detecting STIs caused by
these bacteria. METHODS: Ninety five first-time male attendees of the Genito
urinary Medicine Clinic in Hospital Kuala Lumpur were included in this cross
sectional study. The detection of C. trachomatis was achieved through direct
fluorescence antibody (DFA) staining of urethral swabs and real-time polymerase
chain reaction testing (Xpert(r) CT/NG assay) on urine specimens. N. gonorrhoeae
was detected through Gram staining and culture of urethral swabs and Xpert(r) CT/
NG assay on urine specimens. RESULTS: From the Xpert(r) CT/NG results, 11 (11.6%)
attendees had chlamydia, 23 (24.2%) had gonorrhoea and 8 (8.4%) had both STIs.
The sensitivity and specificity of DFA in detecting chlamydia compared to
Xpert(r) CT/NG were 5.3% (95% CI: 0-28) and 94.7% (95% CI: 86-98), respectively.
For gonorrhoea, the sensitivity and specificity of Gram staining were 90.3% (95%
CI: 73-98) and 95.3% (86-99), respectively, whereas the sensitivity and
specificity of culture compared to Xpert(r) CT/NG were 32.2% (95% CI: 17-51) and
100% (95% CI: 93-100), respectively. CONCLUSION: Although Gram-stained urethral
swab smears are sensitive enough to be retained as a screening tool for
gonorrhoea, culture as well as DFA lack sensitivity and are poorly suited to
screen for gonorrhoea and chlamydia, respectively. However, owing to their high
specificity, conventional detection methods are still suitable as confirmatory
tests for gonorrhoea and chlamydia.
PMID- 28413203
TI - Nuclear morphometry and texture analysis on cytological smears of thyroid
neoplasms: a study of 50 cases.
AB - BACKGROUND: Fine needle aspiration cytology (FNAC) is a reliable and reproducible
diagnostic technique for thyroid lesions with certain limitations. Computed
morphometric methods have been introduced with a view to improve the diagnostic
yield of thyroid aspirates. However, a review of the existing literature revealed
conflicting reports regarding morphometric parameters in thyroid neoplasms.
MATERIALS AND METHODS: This study included 50 cases of thyroid lesions (20 cases
of colloid goitre, 15 of follicular adenoma, 5 of follicular carcinoma and 10
papillary carcinomas). Digital images of cytologic smears of these cases were
captured using a dedicated photomicrography system and nuclear profiles traced
manually. With self-designed image analysis software, nuclear morphometric
measurements, including texture analysis, were performed. Discriminant analysis
was performed including the morphometric parameters and percentage of correctly
classified nuclei noted. RESULTS: Nuclear morphometry parameters showed that
papillary thyroid carcinoma had the highest perimeter, area, radius and
elongation factor compared to other thyroid lesions. Discriminant analysis
revealed that altogether 77.9% of cells could be correctly classified to their
lesion category based on the nuclear morphometric and textural parameters. Of the
neoplastic cases, 84.5% of cells of follicular neoplasms and 72.5% of papillary
carcinoma were classified to the respective category. CONCLUSION: Nuclear
morphometry, including texture analysis, can assist in the cytologic diagnosis of
thyroid lesions, considering the high degree of accuracy of classification.
Further studies and methodological refinements can achieve higher accuracy.
PMID- 28413204
TI - The study of the circannual relationship between the activity of the epiphysis
and gonads in rats of different sex and age.
AB - BACKGROUND: The relationship between the activity of the epiphysis and gonads in
rats of different sex and age in different seasons of the year was determined by
studying the levels of melatonin and testosterone in the blood plasma.
Determination of the levels of melatonin and testosterone in the serum of rats
was carried out by enzyme-linked immunosorbent assay. To assess the relationship
between the levels of melatonin and testosterone the correlation coefficient was
calculated. Based on the study of the levels of melatonin and testosterone in
serum the circannual relationship between the activity of the pineal gland and
gonads in males of reproductive age has been determined. In females, the
relationship between the levels of melatonin and testosterone without the
circannual dependence has been determined. The strongest correlation between
melatonin and testosterone is present in males at the age of 9 months in autumn,
and it corresponds to the human age of 29-30 years.
PMID- 28413205
TI - Oral ketamine induced pathological changes of the urinary tract in a rat model.
AB - INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to
cause urinary tract damage. However, there is little information on the
pathological effects of ketamine from oral administration. We aimed to study the
effects of oral ketamine on the urinary tract and the reversibility of these
changes after cessation of ketamine intake. METHODS: Rats were fed with illicit
(a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg
(N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding
for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for
any potential recovery of pathological changes before being sacrificed for
necropsy. Histopathological examination was performed on the kidney and urinary
bladder. RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed
with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the
control and 100 mg/kg illicit ketamine groups. Renal changes, such as
interstitial nephritis and papillary necrosis, were observed in rats given
illicit ketamine. After ketamine cessation, no inflammation was observed in the
bladder of all rats. However, renal inflammation remained in 60% of the rats
given illicit ketamine. No dose-effect relationship was established between oral
ketamine and changes in the kidneys. CONCLUSION: Oral ketamine caused
pathological changes in the urinary tract, similar to that described in exposure
to parenteral ketamine. The changes in the urinary bladder were reversible after
short-term exposure.
PMID- 28413206
TI - Differential diagnostic significance of HBME-1, CK19 and S100 in various thyroid
lesions.
AB - OBJECTIVE: Due several overlapping histomorphological features and pitfalls in
thyroid pathology, there is need to establish a panel of immunomarkers that would
aid in proper diagnosis. This study was carried out to investigate the ability of
HBME-1, CK19, and S100 in differentiating between hyperplastic, benign and
malignant thyroid lesions. MATERIALS AND METHODS: Immunohistochemical analysis of
60 thyroidectomy specimens (10 hyperplastic nodules, 14 follicular adenomas and
36 malignant thyroid neoplasms) was carried out. The extent and intensity of HBME
1, CK19, and S100 immunoreactivity was assessed in each case. RESULTS: HBME-1
positivity was noted in 86.1% of malignant cases while the majority of the benign
lesions were negative. Diffuse strong CK19 positivity was documented in 27/31
papillary carcinoma whereas all cases of follicular carcinoma and medullary
carcinoma were negative. Most of the hyperplastic nodules and follicular adenomas
were also CK19 negative, although focal weak staining was noted in a few cases.
S100 was positive only in medullary carcinoma. HBME-1 was most sensitive (86.1%)
and specific (87.5%) in distinguishing between benign and malignant thyroid
lesions. The diagnostic accuracy was further increased when HBME-1 was used
simultaneously with CK19/S100/CK19+S100. The sequential use of HBME-1 and CK19
also proved beneficial in discriminating between the various follicular-patterned
thyroid lesions. CONCLUSION: HBME-1 immunolabeling suggests malignancy, whereas
strong diffuse CK19 positivity substantiates papillary differentiation. The
utilization of these markers (alone or in combination) along with
histomorphological evaluation is helpful in the differential diagnosis. S100 has
minimal utility in this regard.
PMID- 28413207
TI - Rate of active Helicobacter pylori infection among symptomatic patients of
Pakistan.
AB - Only few epidemiological studies have examined the rate of active H. pylori
infection in the symptomatic population in Pakistan. This retrospective study
presents the laboratory data collected during the past 13 years (2002 to 2015)
from 2315 symptomatic patients referred to the BreathMAT Lab, Nuclear Medicine,
Oncology and Radiotherapy Institute, Islamabad for the diagnosis of active H.
pylori infection using the 13C Urea Breath Test. Rate of infection and its
association with gender and age were evaluated. The overall rate of active H.
pylori infection was 49.5% and there was no association of this rate of infection
with gender. An increase in rate of infection was observed with increasing age
with significant difference (p < 0.05). The patients that tested negative for
this infection might be having symptoms due to stress and indiscriminate use of
non-steroidal antiinflammatory drugs (NSAIDs) in this community. The fact that
half of the symptomatic patients were negative needs to be highlighted and
further suggests that symptomatic patients should be tested by the 13C UBT before
prescribing antibiotic treatment for H. pylori eradication. In addition, there is
a need to educate this community about the harmful and side effects of self
medication and overuse of NSAIDs.
PMID- 28413208
TI - Anti-M induced severe haemolytic disease of foetus and newborn in a Malay woman
with recurrent pregnancy loss.
AB - Haemolytic disease of the foetus and newborn (HDFN) is caused by maternal red
blood cells (RBC) alloimmunisation resulted from incompatibility of maternal and
foetal RBCs. However, only a few HDFN attributed to anti-M were reported, varying
from asymptomatic to severe anaemia with hydrops foetalis and even intrauterine
death. A case of severe HDFN due to anti-M alloantibody from an alloimmunized
grandmultiparous Malay woman with recurrent pregnancy loss is reported here. The
newborn was delivered with severe and prolonged anaemia which required frequent
RBC transfusions, intensive phototherapy and intravenous immunoglobulin
administration. Although anti-M is rarely known to cause severe HDFN, a careful
serological work-up and close assessment of foetal well-being is important,
similar to the management of RhD HDFN. Alloimmunisation with anti-M type can lead
to severe HDFN and even foetal loss.
PMID- 28413209
TI - Duplication 17p11.2 (Potocki-Lupski Syndrome) in a child with developmental
delay.
AB - Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome,
trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and
a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key
features of such patients are autism spectrum disorder, learning disabilities,
developmental delay, attention-deficit disorder, infantile hypotonia and
cardiovascular abnormalities. Previous studies using microarray identified
variations in the size and extent of the duplicated region of chromosome 17p11.2.
However, there are a few genes which are considered as candidates for PTLS which
include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In this report, we
investigated a case of a 3-year-old girl who has developmental delay. Her
chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH
(4X44 K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome
17p11.2. The result was confirmed by fluorescence in situ hybridization (FISH)
using probes in the critical PTLS region. This report demonstrates the importance
of microarray and FISH in the diagnosis of PTLS.
PMID- 28413210
TI - Acute pulmonary thromboembolism in a case of fatal child abuse.
AB - Child abuse is a worldwide problem. The four major types of abuse include
physical abuse, child neglect, psychological maltreatment and sexual violence. We
describe a fatal case of child abuse which presented with numerous old and recent
soft tissue injuries all over the body. The injuries on the legs have immobilized
the victim for quite some time, giving rise to deep vein thrombosis, leading to
death as a result of acute pulmonary thromboembolism. This case demonstrates
presence of both elements of abuse and neglect in one victim. As this category of
crime involves a helpless child, we would also like to reiterate that the
community has an obligation to prevent such tragedies and educating the public to
recognize the signs and symptoms of abuse would be of utmost important.
Ultimately, the community must also be responsible for reporting such offences
and the act of silence is akin to condoning a crime witnessed.
PMID- 28413211
TI - Vaginal Brenner tumor with literature review: does this tumour originate from
Walthard nests?
AB - Vaginal Brenner tumor is extremely rare. Only five cases have been reported in
the English literature to date. Here we report a vaginal Brenner tumor in a 76
year old postmenopausal woman, who presented with a 2.5cm-sized sessile vaginal
polyp. Microscopically, it showed characteristic features of Brenner tumor
consisting of three components; transitional islands, glands, and dense fibrous
stroma. The epithelial tumor cells were positive for GATA-3, p63 and ER, but
negative for PAX8. The origin of Brenner tumors in the vagina is unclear, but
previous reports suggested of Mullerian origin. However, our case revealed that
vaginal Walthard nests could be possible precursor lesions based on their
immunohistochemical staining results.
PMID- 28413212
TI - Prevalence of BRAFV600E mutation in Asian patients with thyroid cancer.
AB - No abstract available.
PMID- 28413213
TI - Response: Prevalence of BRAFV600E mutation in Asian patients with thyroid cancer.
AB - No abstract available.
PMID- 28413214
TI - Circulating Biomarkers for Predicting Infliximab Response in Rheumatoid
Arthritis: A Systematic Bioinformatics Analysis.
AB - BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid
arthritis (RA). However, many patients responded poorly and related studies were
inconsistent in predictive biomarkers. This study aimed to identify circulating
biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public
databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for
related microarray datasets, focused on the response to infliximab in RA. All
peripheral blood samples were collected before infliximab treatment and gene
expression profiles were measured using microarray. Differential genes associated
with infliximab efficacy were analyzed. The genes recognized by half of the
datasets were regarded as candidate biomarkers and validated by prospective
datasets. RESULTS Eight microarray datasets were identified with 374 blood
samples of RA patients, among which 191 (51.1%) were diagnosed as non-responders
in the subsequent infliximab treatment. Five genes (FKBP1A, FGF12, ANO1, LRRC31,
and AKR1D1) were associated with the efficacy and recognized by half of the
datasets. The 5-gene model showed a good predictive power in random- and
prospective-designed studies, with AUC (area under receiver operating
characteristic [ROC] curve)=0.963 and 1.000, and it was also applicable at the
early phase of treatment (at week 2) for predicting the response at week 14
(AUC=1.000). In the placebo group, the model failed to predict the response
(AUC=0.697), indicating the model's specificity in infliximab treatment.
CONCLUSIONS The model of FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1 in peripheral
blood is useful for efficiently predicting the response to infliximab treatment
in rheumatoid arthritis.
PMID- 28413215
TI - Successful Withdrawal of Insulin Therapy After Post-Treatment Clearance of
Hepatitis C Virus in a Man with Type 2 Diabetes.
AB - BACKGROUND Chronic hepatitis C virus (HCV) infection is associated with increased
insulin resistance and risk of type 2 diabetes. Successful antiviral treatment
can improve insulin resistance and allow a reduction in blood glucose-lowering
treatment. There have been case reports of a reduced insulin requirement in this
situation, although 1 case in which insulin was stopped exhibited a subsequent
deterioration in glycemic control. CASE REPORT A 55-year-old Italian man was
diagnosed with HCV infection in 2000 at the age of 39 years and with type 2
diabetes 6 years later. He was started on metformin but progressed to multiple
daily insulin injections after 3 years. He was treated with pegylated interferon,
ribavirin, and telaprevir over 12 months from early 2013, and achieved a
sustained virologic response and normalization of hepatic function within 6
months of starting therapy. He was subsequently able to reduce his insulin doses
from 0.56 to 0.44 U/kg/day over the next 2 years and, based on a random serum C
peptide of 1.73 nmol/L (fasting reference range 0.37-1.47 nmol/L) in the presence
of serum glucose 7.9 mmol/L (143 mg/dL) and negative glutamic acid decarboxylase
antibodies, he accelerated withdrawal and stopped insulin 6 months later. He is
currently taking linagliptin 5 mg daily with good glycemic control. His body mass
index and HbA1c have remained <25 kg/m2 and <6.0% (<42 mmol/mol), respectively,
throughout. CONCLUSIONS This case shows that complete withdrawal of long-term
insulin therapy may be possible after HCV treatment has induced a sustained
virologic response.
PMID- 28413216
TI - Uncompromised NK cell activation is essential for virus-specific CTL activity
during acute influenza virus infection.
AB - Natural killer (NK) cells are indispensable components of both the innate and
adaptive immune response. However, their precise roles in the cross-talk between
innate and adaptive immunity during influenza virus infection remain
controversial. By comparing NK cell dynamics and activity under a sub-lethal dose
and high dose of influenza virus infection, we showed that influenza virus PR8
directly infected NK cells during natural infection, which was consistent with
our previous findings obtained from an in vitro investigation of human NK cells.
The impairments in cytotoxicity and IFN-gamma production by spleen NK cells
following high-dose infection were accompanied by decreased virus-specific
killing mediated by cytotoxic T lymphocytes (CTLs). Importantly, the weakened CTL
activity could be reversed by adoptive transfer of spleen NK cells harvested from
low-dose-infected mice but not healthy donors. Taken together, our data provide
direct evidence supporting the contribution of NK cells to antiviral T-cell
responses. This study also indicates that a novel NK-targeted immune evasion
strategy is used by influenza virus to shrink both innate and adaptive immune
responses.
PMID- 28413218
TI - Understanding how low-socioeconomic status households cope with health shocks: An
analysis of multi-sector linked data.
AB - Low-socioeconomic status (SES) households have little income or wealth to buffer
against the negative impacts of an adverse health event (health shock) among
adult household members. However, these households may employ a variety of other
coping strategies such as receiving help from family, friends, and social
services. Administrative data from a non-profit food distribution center,
electronic medical record (EMR) data from a safety-net healthcare system, and
publicly available residential appraisal data were linked to provide insight into
these coping strategies. Three broad types of coping strategies were examined:
changes in household structure, residential mobility, and utilization of social
services. Of 3,235 households, 20.2% had at least one adult member who
experienced a health shock. These households were more likely to gain additional
adult household members and employed household members, were more likely to move
residence and to move distances greater than one mile, and were less likely to
visit the food distribution center after the shock.
PMID- 28413219
TI - Contemporary biopsychosocial exercise prescription for chronic low back pain:
questioning core stability programs and considering context.
AB - This commentary explores the importance of considering the biopsychosocial model
and contextual factors when prescribing exercise. Diverse exercise programs for
patients with chronic low back pain (CLBP) produce similar outcomes, without one
specific exercise protocol demonstrating clear superiority. One clear barrier to
positive outcomes is poor exercise adherence. We suggest that there are certain
common contextual factors present in all exercise prescription scenarios that may
impact adherence and health-related outcomes. While challenging common core
stability exercise prescription, we present an argument for enhancing and
intentionally shaping the following contextual factors: the therapeutic alliance,
patient education, expectations and attributions of therapeutic success or
failure, and mastery or cognitive control over a problem. Overall, this
commentary argues that to improve exercise adherence and outcomes in the CLBP
population, the context in which exercise is delivered and the meaning patients
embody need to be considered and shaped by clinicians.
PMID- 28413220
TI - The physical and psychological impact of neurogenic claudication: the patients'
perspectives.
AB - BACKGROUND: The patient perspective regarding the impact of neurogenic
claudication (NC) has not been well studied. The objectives of this study were to
determine what is most bothersome among patients with NC and how it impacts their
lives and expectations with surgical and non-surgical treatment. METHODS: Semi
structured telephone interviews were conducted, audio recorded and transcribed
verbatim. A thematic analysis categorized key findings based on relative
importance and impact on participants. RESULTS: Twenty-eight individuals
participated in this study. Participants were most bothered by the pain of NC,
which dramatically impacted their lives. Inability to walk was the dominant
functional limitation and this impacted the ability to engage in recreational and
social activities. The most surprising finding was how frequently participants
reported significant emotional effects of NC. CONCLUSIONS: From a patients'
perspective NC has a significant multidimensional effects with pain, limited
walking ability and emotional effects being most impactful to their lives.
PMID- 28413221
TI - A proposed in vitro model for investigating the mechanisms of 'joint cracking': a
short report of preliminary techniques and observations.
AB - Joint "cracking" is common but not a clearly understood audible phenomenon. In
this brief report we propose an in-vitro model to potentially assist in revealing
a mechanism for, and therefore source of, this phenomenon. Using a suction cup
under tension and de-nucleated fluid to simulate synovial fluid, an audible
release with intra-articular cavity formation was elicited. This was followed by
a refractory period during which no audible crack could be elicited until the
observed cavity had slowly reabsorbed back into the joint fluid. Conversely, if
regular fluid containing pre-existing nuclei was used, a cavity formation
occurred but with neither an audible release nor subsequent refractory period.
With this simple in-vitro model, we were able to reproduce the characteristic
audible release, cavity formation and related refractory period typically
observed in related experiments in human joints. This simple in-vitro model may
be of use in helping to discern both the timing and precise nature of other yet
to be discerned mechanisms related to joint cracking.
PMID- 28413217
TI - Lymphotoxin signalling in tertiary lymphoid structures and immunotherapy.
AB - Tertiary lymphoid structures (TLS) often develop at sites of persistent
inflammation, including cancers and autoimmune diseases. In most cases, the
presence of TLS correlates with active immune responses. Because of their
proximity to pathological loci, TLS are an intriguing target for the manipulation
of immune responses. For several years, it has become clear that lymphotoxin (LT)
signalling plays critical roles in lymphoid tissue organogenesis and maintenance.
In the current review, we will discuss the role of LT signalling in the
development of TLS. With a focus on cancers and autoimmune diseases, we will
highlight the correlations between TLS and disease progression. We will also
discuss the current efforts and potential directions for manipulating TLS for
immunotherapies.
PMID- 28413222
TI - Calcium pyrophosphate deposition disease in the ankle joint: a case report.
AB - OBJECTIVE: To detail the presentation of calcium pyrophosphate deposition disease
(CPPD) in the ankle joint. The aim of this case report is to inform health-care
practitioners about the presentation of this condition in an uncommon location
and discuss the diagnosis, potential treatment, and management strategies for a
patient with CPPD. CLINICAL FEATURES: A 36-year-old male patient presented to a
chiropractic clinic with an acute, painful, and swollen ankle, which was later
diagnosed by plain film radiograph as CPPD. A rheumatology follow-up was
recommended and at-home treatment was prescribed to treat acute symptoms and
monitor progress. OUTCOME: No chiropractic treatment was provided and the patient
has been referred to a rheumatologist for further assessment. The diagnosis of
CPPD was confirmed and he was advised to take an anti-inflammatory if symptoms
recurred and booked for further follow-up in six months. SUMMARY: Although the
presentation is less common, CPPD can present in the ankle joint and mimic other
inflammatory disorders. Conservative treatment can be applied to treat acute
symptoms and referral to a rheumatologist is suggested to monitor progress of
this condition.
PMID- 28413223
TI - Chiropractic management of a geriatric patient with idiopathic neuralgic
amyotrophy: a case report.
AB - OBJECTIVE: The purpose of this paper is to describe chiropractic management of a
patient with neuralgic amyotrophy (NA) and to provide discussion regarding
presentation, differential diagnosis, management and prognosis of idiopathic NA.
CASE PRESENTATION: An 85 year old Caucasian male presented to a chiropractic
clinic with right periscapular and lateral rib cage pain. The patient had
previously sought evaluation and treatment from multiple health care providers
and underwent multiple interventions without relief. INTERVENTION AND OUTCOME:
The patient was managed with a course of chiropractic care and an ongoing home
exercise program was carried out. The patient reported spontaneous resolution of
pain approximately 14 months post onset. SUMMARY: NA is a poorly known clinical
entity amongst health care providers and poses challenges in timely and proper
diagnosis. Recognition of NA is important for patients to be best managed and for
more optimal patient outcomes to be achieved.
PMID- 28413225
TI - Pathological burst fracture in the cervical spine with negative red flags: a 12
year follow-up.
AB - In 2004, a 61-year-old male presented to a chiropractic clinic complaining of
neck pain after hearing a 'crunch' when getting out of bed that morning. The
initial history intake and physical examination identified no red flags or
indications for the patient's pain, with the exception of traction being pain
provoking. Conventional radiographs were ordered, which identified a pathological
burst fracture of the fourth cervical vertebra. This Imaging Case Review (ICR) is
to provide clinicians with a follow-up to the patient's care and current state.
PMID- 28413224
TI - Selecting and training opinion leaders and best practice collaborators:
experience from the Canadian Chiropractic Guideline Initiative.
AB - OBJECTIVES: To describe the process for selecting and training chiropractic
opinion leaders (OLs) and best practice collaborators (BPCs) to increase the
uptake of best practice. METHODS: In Phase 1, OLs were identified using a cross
sectional survey among Canadian chiropractic stakeholders. A 10-member committee
ranked nominees. Top-ranked nominees were invited to a training workshop. In
Phase 2, a national e-survey was administered to 7200 Canadian chiropractors to
identify additional OLs and BPCs. Recommended names were screened by OLs and
final selection made by consensus. Webinars were utilized to train BPCs to engage
peers in best practices, and facilitate guideline dissemination. RESULTS: In
Phase 1, 21 OLs were selected from 80 nominees. Sixteen attended a training
workshop. In Phase 2, 486 chiropractors recommended 1126 potential BPCs, of which
133 were invited to participate and 112 accepted. CONCLUSIONS: OLs and BPCs were
identified across Canada to enhance the uptake of research among chiropractors.
PMID- 28413226
TI - Grade V acromioclavicular joint separation in a 57-year-old mountain biker.
AB - Patients rarely present to a chiropractic office setting during the acute stage
of a high-grade (i.e. Rockwood types IV-VI) separation of the acromioclavicular
(AC) joint. Moreover, such cases are non-existent in the peer-reviewed
chiropractic literature. Some controversy exists over the optimal (surgical vs.
non-surgical) treatment of severe AC joint injuries. Published reports of
nonoperative management for grade V injuries of the AC joint are also scarce.
This case review highlights the plain film imaging and conservative management of
a 57-year-old patient diagnosed with an acute Rockwood type V AC joint
separation. Radiographs with nine years of follow-up are presented.
PMID- 28413227
TI - David C. Drum, DC, FCCS(C): an accomplished, multi-faceted individual.
AB - Pablo Picasso (1881-1973) is quoted as saying, "The meaning of life is to find
your gift. The purpose of life is to give it away." With these few words Picasso
captures the essence of David Drum's existence. From his birth in Moncton, NB,
through his formal education in Toronto, ON, to his so-called "retirement" in
Crystal Beach, ON, this paper spans 72 years, unveiling the broad range of
opportunities for growth David Drum has encountered in his life's journey and
documenting his acceptance of the obligations for proud philanthropy that
accompany them. Dr. Drum's many accomplishments, gifts, and contributions to the
profession and world of art are discussed.
PMID- 28413228
TI - Air Breathing Cathodes for Microbial Fuel Cell using Mn-, Fe-, Co- and Ni
containing Platinum Group Metal-free Catalysts.
AB - The oxygen reduction reaction (ORR) is one of the major factors that is limiting
the overall performance output of microbial fuel cells (MFC). In this study,
Platinum Group Metal-free (PGM-free) ORR catalysts based on Fe, Co, Ni, Mn and
the same precursor (Aminoantipyrine, AAPyr) were synthesized using identical
sacrificial support method (SSM). The catalysts were investigated for their
electrochemical performance, and then integrated into an air-breathing cathode to
be tested in "clean" environment and in a working microbial fuel cell (MFC).
Their performances were also compared to activated carbon (AC) based cathode
under similar conditions. Results showed that the addition of Mn, Fe, Co and Ni
to AAPyr increased the performances compared to AC. Fe-AAPyr showed the highest
open circuit potential (OCP) that was 0.307 +/- 0.001 V (vs. Ag/AgCl) and the
highest electrocatalytic activity at pH 7.5. On the contrary, AC had an OCP of
0.203 +/- 0.002 V (vs. Ag/AgCl) and had the lowest electrochemical activity. In
MFC, Fe-AAPyr also had the highest output of 251 +/- 2.3 MUWcm-2, followed by Co
AAPyr with 196 +/- 1.5 MUWcm-2, Ni-AAPyr with 171 +/- 3.6 MUWcm-2, Mn-AAPyr with
160 +/- 2.8 MUWcm-2 and AC 129 +/- 4.2 MUWcm-2. The best performing catalyst (Fe
AAPyr) was then tested in MFC with increasing solution conductivity from 12.4
mScm-1 to 63.1 mScm-1. A maximum power density of 482 +/- 5 MUWcm-2 was obtained
with increasing solution conductivity, which is one of the highest values
reported in the field.
PMID- 28413229
TI - Quality of maize for sale in markets in Benin and Niger.
AB - A follow-up study on the quality of maize for sale in West African public markets
was carried out in Benin and Niger from August 15-28, 2013. Complementing the
earlier study, this present assessment included not only retailers but also
wholesalers and maize producers. Samples were evaluated for parameters related to
the physical quality of the maize and for aflatoxin contamination. Most maize
value chain actors process their offered grain using traditional methods for
threshing, winnowing and drying. Maize for sale in the markets surveyed had an
average moisture content ranging between 12 and 14%. Non-grain impurities
amounted to 0-2.3% while mouldy grains ranged between 0.2 and 0.8%. The impurity
level in grain was three times higher among wholesalers compared to retailers and
producers. An insect pest, the Larger Grain Borer (Prostephanus truncatus (Horn)
was found only in Benin but Sitophilus zeamais Motschulsky, Cryptolestes
ferrugineus Stephens, and Tribolium castaneum Herbst, were present in maize for
sale in the markets in of both countries. Insect pest frequency was 16 times
higher in wholesalers' grain compared to that of retailers and producers.
Aflatoxin levels exceeding the accepted standard of 20 ppb were noted in markets
in both countries. The highest proportion of aflatoxin-contaminated maize was in
wholesalers' grain in Malanville market.
PMID- 28413230
TI - The relative effects of upwelling and river flow on the phytoplankton diversity
patterns in the ria of A Coruna (NW Spain).
AB - Phytoplankton species assemblages in estuaries are connected to those in rivers
and marine environments by local hydrodynamics leading to a continuous flow of
taxa. This study revealed differential effects of upwelling and river flow on
phytoplankton communities observed in 2011 along a salinity gradient from a river
reservoir connected to the sea through a ria-marine bay system in A Coruna (NW
Spain, 43 degrees 16-21' N, 8 degrees 16-22' W). With 130 phytoplankton taxa
identified, the assemblages were dominated in general by diatoms, particularly
abundant in the bay and in the estuary, but also by chlorophycea and
cyanobacteria in the reservoir. Considering the entire seasonal cycle, the local
assemblages were mainly characterized by changes in cryptophytes and diatoms,
small dinoflagellates and some freshwater chlorophycea. Salinity, nitrate, and
organic matter variables, were the main environmental factors related to the
changes in the phytoplankton communities through the system, while phosphate and
nitrite were also important for local communities in the estuary and the bay,
respectively. The corresponding local phytoplankton assemblages showed moderate
levels of connectivity. The estuarine community shared a variable number of taxa
with the adjacent zones, depending on the relative strength of upwelling (major
influence from the bay) and river flow (major influence of the reservoir) but had
on average 35% of unique taxa. Consequently, local and zonal diversity patterns
varied seasonally and were not simply related to the salinity gradient driven by
the river flow.
PMID- 28413231
TI - Development of a roof bolter canopy air curtain for respirable dust control.
AB - Testing of the roof bolter canopy air curtain (CAC) designed by the U.S. National
Institute for Occupational Safety and Health (NIOSH) has gone through many
iterations, demonstrating successful dust control performance under controlled
laboratory conditions. J.H. Fletcher & Co., an original equipment manufacturer of
mining equipment, further developed the concept by incorporating it into the
design of its roof bolting machines. In the present work, laboratory testing was
conducted, showing dust control efficiencies ranging from 17.2 to 24.5 percent.
Subsequent computational fluid dynamics (CFD) analysis revealed limitations in
the design, and a potential improvement was analyzed and recommended. As a
result, a new CAC design is being developed, incorporating the results of the
testing and CFD analysis.
PMID- 28413232
TI - The freshwater red alga Batrachospermum turfosum (Florideophyceae) can acclimate
to a wide range of light and temperature conditions.
AB - Batrachospermum turfosum Bory is one of the generalists among the few red algae
that have adapted to freshwater habitats, occurring in a variety of primarily
shaded, nutrient-poor micro-habitats with lotic (running) or lentic (standing)
waters. Seasonal variations in water level and canopy cover can expose this
sessile alga to widely fluctuating temperatures, solar irradiation and nutrient
availability. Here we report on the ecophysiology of B. turfosum collected from
an ultra-oligotrophic bog pool in the Austrian Alps. Photosynthesis as a function
of photon fluence density (PFD) and temperature was studied by measuring oxygen
evolution in combination with chlorophyll fluorescence. In addition, the effects
of ultraviolet radiation (UVR) on photosynthetic pigments were analysed using
HPLC and spectrophotometric methods, and cellular ultrastructure was studied
using transmission electron microscopy. We found that B. turfosum is adapted to
low light, with a light compensation point (Ic) and a light saturation point (Ik)
of 8.4 and 29.7 MUmol photons m- 2 s-1, respectively, but also tolerates higher
PFDs of ~1000 MUmol photons m-2 s-1, and is capable of net photosynthesis at
temperatures between 5 degrees C and 35 degrees C. Exposure to either UV-A or UV
AB for 102 h led to a strong transient drop in effective quantum yield
(DeltaF/FM'), followed by an acclimation to about 70% of initial DeltaF/FM'
values. Ultrastructural changes included the accumulation of plastoglobules and
dilated membranes after UVR treatment. Although all photosynthetic pigments
strongly decreased upon UVR exposure and no UV-photoprotectants (e.g. mycosporine
like amino acids) could be detected, the alga was capable of recovering
DeltaF/FM' and phycobiliproteins after UVR treatment. In summary, B. turfosum
tolerates a wide range of irradiation and temperature regimes, and these traits
may be the basis for its successful adaptation to challenging environments.
PMID- 28413233
TI - An alternative synthesis of Vandetanib (CaprelsaTM) via a microwave accelerated
Dimroth rearrangement.
AB - Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment
of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline,
using harsh reagents, in addition to requiring sequential protection and
deprotection steps. In the present work, use of the Dimroth rearrangement in the
key quinazoline forming step enabled the synthesis of Vandetanib in nine steps
(compared to the previously reported 12-14).
PMID- 28413234
TI - High-dimensional tests for functional networks of brain anatomic regions.
AB - Exploring resting-state brain functional connectivity of autism spectrum
disorders (ASD) using functional magnetic resonance imaging (fMRI) data has
become a popular topic over the past few years. The data in a standard brain
template consist of over 170,000 voxel specific points in time for each human
subject. Such an ultra-high dimensionality makes the voxel-level functional
connectivity analysis (involving four billion voxel pairs) both statistically and
computationally inefficient. In this work, we introduce a new framework to
identify the functional brain network at the anatomical region level for each
individual. We propose two pairwise tests to detect region dependence, and one
multiple testing procedure to identify global structures of the network. The
limiting null distribution of each test statistic is derived. It is also shown
that the tests are rate optimal when the alternative block networks are sparse.
The numerical studies show that the proposed tests are valid and powerful. We
apply our method to a resting-state fMRI study on autism and identify patient
unique and control-unique hub regions. These findings are biologically meaningful
and consistent with the existing literature.
PMID- 28413235
TI - Comparison of total and aqua regia extractability of heavy metals in sewage
sludge: The case study of a certified reference material.
AB - A number of different digestion methods, including aqua regia extraction
following two ISO guides were used in an inter-laboratory comparison study. The
results obtained showed comparable values for the total and aqua regia
extractable content of As, Cu, Fe, Hg, Pb and Zn, while Cd, Co and Cr results
were about 10% lower when aqua regia was employed. This small difference was
covered by the between-laboratory relative standard deviation of the
measurements; therefore in this study no difference in the extraction of the
elements by the employed methods was found. The high organic matter content,
together with low SiO2 and refractory aluminium and iron oxide amount as well as
the small particle size of the sewage sludge material was reputed to have an
effect on the extracting capacity of a weaker solvent such as aqua regia,
bringing its results close to the total content ones.
PMID- 28413237
TI - In Space and Time: Territorial Animals are Attracted to Conspecific Chemical
Cues.
AB - Territorial animals lay scent marks around their territories to broadcast their
presence, but these olfactory signals can both attract and repel con-specifics.
Attraction or aversion can have a profound impact in terms of space use and
thereby influence an individual's access to resources and mates. Here, we test
the impact of chemical signals on the long-term space use and activity of
receivers, comparing the response of males and females, territory holders, and
temporary visitors in Sceloporus undulatus lizards in the field. We placed either
male femoral gland secretions (chemical) or blank (control) cues on resident male
landmarks, repeatedly over 5 d, while monitoring the activity and location of all
lizards in the vicinity. We found that resident males and females, but not non
resident males, were active on more days near landmarks treated with chemical
cues than landmarks treated with control cues. Non-resident males remained closer
to chemical than control cues. These results suggest that territorial scent marks
are attractive to conspecifics and impact space use, but that the specific
effects depend on receiver sex and residency status. Such subtle or gradual
changes in behavior may frequently be overlooked by short-term choice
experiments. Future studies investigating the behavioral significance of a
communicative signal should consider these finer details of behavior for a more
comprehensive assessment.
PMID- 28413236
TI - Scopulariopsis and scopulariopsis-like species from indoor environments.
AB - Scopulariopsis-like species are often reported from the indoor environment, as
well as from clinical samples. The lack of type isolates and thorough
phylogenetic studies in the Microascaceae hampered the correct identification of
these isolates. Based on recent phylogenetic studies, which resulted in multiple
name changes, the aim is to molecularly identify the Scopulariopsis and
scopulariopsis-like species which occur in the indoor environment and give an
overview of the current species in these genera and their habitats. Strains from
the CBS culture collection were supplemented with almost 80 indoor strains of
which the internal transcribed spacer 1 and 2 and intervening 5.8S nrDNA (ITS),
beta-tubulin (tub2) and translation elongation factor 1-alpha (tef1) gene regions
were sequenced for phylogenetic inference. The multi-gene phylogenies recognise
33 Microascus species and 12 Scopulariopsis species and showed that the recently
established genus Fuscoannellis, typified by Scopulariopsis carbonaria, should be
synonymized with the genus Yunnania. Seven new Microascus species, four new
Scopulariopsis species, and one new Yunnania species, are described, and a new
name in Microascus and two new name combinations (one in Microascus, and one in
Yunnania) are proposed. In the indoor environment 14 Microascus species and three
Scopulariopsis species were found. Scopulariopsis brevicaulis (22 indoor
isolates) and Microascus melanosporus (19 indoor isolates) are the most common
indoor species, in number of isolates, followed by M. paisii (8 indoor isolates)
and S. candida (7 indoor isolates). A genus phylogeny based on the ITS, tef1 and
the large subunit 28S nrDNA (LSU) of the type or representative isolates of all
here recognised species is provided depicting all species habitats. No
correlation between phylogenetic relationship and habitat preference could be
observed. Ten species which are found indoor are also found in relation with
human-derived samples. A table showing recent name changes and a key to common
species of Scopulariopsis and scopulariopsis-like genera found indoors is
included.
PMID- 28413238
TI - Formation of Gold(III) Alkyls from Gold Alkoxide Complexes.
AB - The gold(III) methoxide complex (C?N?C)AuOMe (1) reacts with tris(p
tolyl)phosphine in benzene at room temperature under O abstraction to give the
methylgold product (C?N?C)AuMe (2) together with O=P(p-tol)3 ((C?N?C) = [2,6
(C6H3t Bu-4)2pyridine]2-). Calculations show that this reaction is energetically
favorable (DeltaG = -32.3 kcal mol-1). The side products in this reaction, the
Au(II) complex [Au(C?N?C)]2 (3) and the phosphorane (p-tol)3P(OMe)2, suggest that
at least two reaction pathways may operate, including one involving (C?N?C)Au*
radicals. Attempts to model the reaction by DFT methods showed that PPh3 can
approach 1 to give a near-linear Au-O-P arrangement, without phosphine
coordination to gold. The analogous reaction of (C?N?C)AuOEt, on the other hand,
gives exclusively a mixture of 3 and (p-tol)3P(OEt)2. Whereas the reaction of
(C?N?C)AuOR (R = But, p-C6H4F) with P(p-tol)3 proceeds over a period of hours,
compounds with R = CH2CF3, CH(CF3)2 react almost instantaneously, to give 3 and
O=P(p-tol)3. In chlorinated solvents, treatment of the alkoxides (C?N?C)AuOR with
phosphines generates [(C?N?C)Au(PR3)]Cl, via Cl abstraction from the solvent.
Attempts to extend the synthesis of gold(III) alkoxides to allyl alcohols were
unsuccessful; the reaction of (C?N?C)AuOH with an excess of CH2=CHCH2OH in
toluene led instead to allyl alcohol isomerization to give a mixture of gold
alkyls, (C?N?C)AuR' (R' = -CH2CH2CHO (10), -CH2CH(CH2OH)OCH2CH=CH2 (11)), while 2
methallyl alcohol affords R' = CH2CH(Me)CHO (12). The crystal structure of 11 was
determined. The formation of Au-C instead of the expected Au-O products is in
line with the trend in metal-ligand bond dissociation energies for Au(III): M-H >
M-C > M-O.
PMID- 28413239
TI - Tuning the Si-N Interaction in Metalated Oligosilanylsilatranes.
AB - Most known silatrane chemistry is concerned with examples where the attached
silatrane substituent atom is that of an element more electronegative than
silicon. The current study features silylated silatranes with a range of
electropositive elements attached to the silyl group. The resulting compounds
show different degrees of electron density on the silatrane-substituted silicon
atom. This directly affects the Si-N interaction of the silatrane which can be
monitored either by 29Si NMR spectroscopy or directly by single crystal XRD
analysis of the Si-N distance. Within the sample of study the Si-N distance is
increased from 2.153 to 3.13 A. Moreover, the bis(trimethylsilyl)silatranylsilyl
unit was studied as a substituent for disilylated germylene adducts.
PMID- 28413240
TI - Detection of increased vasa vasorum in artery walls: Improving CT number accuracy
using image deconvolution.
AB - Changes in arterial wall perfusion are an indicator of early atherosclerosis.
This is characterized by an increased spatial density of vasa vasorum (VV), the
micro-vessels that supply oxygen and nutrients to the arterial wall. Detection of
increased VV during contrast-enhanced computed tomography (CT) imaging is limited
due to contamination from blooming effect from the contrast-enhanced lumen. We
report the application of an image deconvolution technique using a measured
system point-spread function, on CT data obtained from a photon-counting CT
system to reduce blooming and to improve the CT number accuracy of arterial wall,
which enhances detection of increased VV. A phantom study was performed to assess
the accuracy of the deconvolution technique. A porcine model was created with
enhanced VV in one carotid artery; the other carotid artery served as a control.
CT images at an energy range of 25-120 keV were reconstructed. CT numbers were
measured for multiple locations in the carotid walls and for multiple time
points, pre and post contrast injection. The mean CT number in the carotid wall
was compared between the left (increased VV) and right (control) carotid
arteries. Prior to deconvolution, results showed similar mean CT numbers in the
left and right carotid wall due to the contamination from blooming effect,
limiting the detection of increased VV in the left carotid artery. After
deconvolution, the mean CT number difference between the left and right carotid
arteries was substantially increased at all the time points, enabling detection
of the increased VV in the artery wall.
PMID- 28413241
TI - Development of Portable Aerosol Mobility Spectrometer for Personal and Mobile
Aerosol Measurement.
AB - We describe development of a Portable Aerosol Mobility Spectrometer (PAMS) for
size distribution measurement of submicrometer aerosol. The spectrometer is
designed for use in personal or mobile aerosol characterization studies and
measures approximately 22.5 * 22.5 * 15 cm and weighs about 4.5 kg including the
battery. PAMS uses electrical mobility technique to measure number-weighted
particle size distribution of aerosol in the 10-855 nm range. Aerosol particles
are electrically charged using a dual-corona bipolar corona charger, followed by
classification in a cylindrical miniature differential mobility analyzer. A
condensation particle counter is used to detect and count particles. The mobility
classifier was operated at an aerosol flow rate of 0.05 L/min, and at two
different user-selectable sheath flows of 0.2 L/min (for wider size range 15-855
nm) and 0.4 L/min (for higher size resolution over the size range of 10.6-436
nm). The instrument was operated in voltage stepping mode to retrieve the size
distribution, which took approximately 1-2 minutes, depending on the
configuration. Sizing accuracy and resolution were probed and found to be within
the 25% limit of NIOSH criterion for direct-reading instruments (NIOSH 2012).
Comparison of size distribution measurements from PAMS and other commercial
mobility spectrometers showed good agreement. The instrument offers unique
measurement capability for on-person or mobile size distribution measurements of
ultrafine and nanoparticle aerosol.
PMID- 28413242
TI - Agriculture in Africa - Telling myths from facts: A synthesis.
AB - Stylized facts drive research agendas and policy debates. Yet robust stylized
facts are hard to come by, and when available, often outdated. The 12 papers in
this Special Issue revisit conventional wisdom on African agriculture and its
farmers' livelihoods using nationally representative surveys from the Living
Standards Measurement Study-Integrated Surveys on Agriculture Initiative in six
African countries. At times they simply confirm our common understanding of the
topic. But they also throw up a number of surprises, redirecting policy debates
while fine-tuning others. Overall, the project calls for more attention to
checking and updating our common wisdom. This requires nationally representative
data, and sufficient incentives among researchers and policymakers alike. Without
well-grounded stylized facts, they can easily be profoundly misguided.
PMID- 28413243
TI - Ten striking facts about agricultural input use in Sub-Saharan Africa.
AB - Conventional wisdom holds that Sub-Saharan African farmers use few modern inputs
despite the fact that most poverty-reducing agricultural growth in the region is
expected to come largely from expanded use of inputs that embody improved
technologies, particularly improved seed, fertilizers and other agro-chemicals,
machinery, and irrigation. Yet following several years of high food prices,
concerted policy efforts to intensify fertilizer and hybrid seed use, and
increased public and private investment in agriculture, how low is modern input
use in Africa really? This article revisits Africa's agricultural input
landscape, exploiting the unique, recently collected, nationally representative,
agriculturally intensive, and cross-country comparable Living Standard
Measurement Study-Integrated Surveys on Agriculture (LSMS-ISA) covering six
countries in the region (Ethiopia, Malawi, Niger, Nigeria, Tanzania, and Uganda).
Using data from over 22,000 households and 62,000 agricultural plots, we offer
ten potentially surprising facts about modern input use in Africa today.
PMID- 28413244
TI - Agricultural intensification: The status in six African countries.
AB - Boserup and Ruthenberg (BR) provided the framework to analyze the impact of
population growth and market access on the intensification of farming systems.
Prior evidence in Africa is consistent with the framework. Over the past two
decades, rapid population growth has put farming systems under stress, while
rapid urbanization and economic growth have provided new market opportunities.
New measures of agro-ecological potential and urban gravity are developed to
analyze their impact on population density and market access. The descriptive and
regression analyses show that the patterns of intensification across countries
are only partially consistent with the BR predictions. Fallow areas have
disappeared, but cropping intensities remain very low. The use of organic and
chemical fertilizers is too low to maintain soil fertility. Investments in
irrigation are inadequate. In light of the promising outcomes suggested by the
Boserup-Ruthenberg framework, the process of intensification across these
countries appears to have been weak.
PMID- 28413245
TI - Is increasing inorganic fertilizer use for maize production in SSA a profitable
proposition? Evidence from Nigeria.
AB - Inorganic fertilizer use across Sub-Saharan Africa is generally considered to be
low. Yet, the notion that fertilizer use is too low is predicated on the
assumption that it is profitable to use rates higher than currently observed.
There is, however, limited empirical evidence to support this. Using a nationally
representative panel dataset, this paper empirically estimates the profitability
of fertilizer use for maize production in Nigeria. We find that fertilizer use in
Nigeria is not as low as conventional wisdom suggests. Low marginal physical
product and high transportation costs significantly reduce the profitability of
fertilizer use. Apart from reduced transportation costs, other constraints such
as soil quality, timely access to the product, and availability of complementary
inputs such as improved seeds, irrigation and credit, as well as good management
practices are also necessary for sustained agricultural productivity
improvements.
PMID- 28413246
TI - How much of the labor in African agriculture is provided by women?
AB - The contribution of women to labor in African agriculture is regularly quoted in
the range of 60-80%. Using individual, plot-level labor input data from
nationally representative household surveys across six Sub-Saharan African
countries, this study estimates the average female labor share in crop production
at 40%. It is slightly above 50% in Malawi, Tanzania, and Uganda, and
substantially lower in Nigeria (37%), Ethiopia (29%), and Niger (24%). There are
no systematic differences across crops and activities, but female labor shares
tend to be higher in households where women own a larger share of the land and
when they are more educated. Controlling for the gender and knowledge profile of
the respondents does not meaningfully change the predicted female labor shares.
The findings question prevailing assertions regarding substantial gains in
aggregate crop output as a result of increasing female agricultural productivity.
PMID- 28413247
TI - Agricultural factor markets in Sub-Saharan Africa: An updated view with formal
tests for market failure.
AB - This paper uses the recently collected Living Standard Measurement Study
Integrated Surveys on Agriculture Initiative data sets from five countries in Sub
Saharan Africa to provide a comprehensive overview of factor market participation
by agrarian households and to formally test for failures in rural markets. Under
complete and competitive markets, households can solve their consumption and
production problems separately, so that household factor endowments do not
predict input demand. This paper implements a simple, theoretically grounded test
of this separation hypothesis, which can be interpreted as a reduced form test of
market failure. In all five study countries, the analysis finds strong evidence
of factor market failure. Moreover, those failures appear general and structural,
not specific to subpopulations defined by gender, geography, human capital, or
land quality. However, we show that rural markets are not generally missing in an
absolute sense, suggesting that market existence is less of a problem than market
function.
PMID- 28413248
TI - Smallholders' land access in Sub-Saharan Africa: A new landscape?
AB - While scholars long recognized the importance of land markets as a key driver of
rural non-farm development and transformation in rural areas, evidence on the
extent of their operation and the nature of participants remains limited. We use
household data from 6 countries to show that there is great potential for such
markets to increase productivity and equalize factor ratios. While rental markets
transfer land to land-poor and labor-rich producers, their operation and thus
impact may be constrained by policy restrictions. Their functioning may also be
constrained by ill-defined or insecure rights that may arise from failure to
fully compensate existing rights in cases of expropriation, a failure to
implement more broadly land policies or to do so in a gender sensitive manner.
Methodological and substantive conclusions are derived.
PMID- 28413249
TI - Agricultural input credit in Sub-Saharan Africa: Telling myth from facts.
AB - Recent evidence shows that many Sub-Saharan African farmers use modern inputs,
but there is limited information on how these inputs are financed. We use recent
nationally representative data from four countries to explore input financing and
the role of credit therein. A number of our results contradict "conventional
wisdom" found in the literature. Our results consistently show that traditional
credit use, formal or informal, is extremely low (across credit type, country,
crop and farm size categories). Instead, farmers primarily finance modern input
purchases with cash from nonfarm activities and crop sales. Tied output-labor
arrangements (which have received little empirical treatment in the literature)
appear to be the only form of credit relatively widely used for farming.
PMID- 28413250
TI - Agricultural commercialization and nutrition revisited: Empirical evidence from
three African countries.
AB - The transition from subsistence to commercial agriculture is key for economic
growth. But what are the consequences for nutritional outcomes? The evidence to
date has been scant and inconclusive. This study contributes to the debate by
revisiting two prevailing wisdoms: (a) market participation by African
smallholders remains low; and (b) the impact of commercialization on nutritional
outcomes is generally positive. Using nationally representative data from three
African countries, the analysis reveals high levels of commercialization by even
the poorest and smallest landholders, with rates of market participation as high
as 90%. Female farmers participate less, but tend to sell larger shares of their
production, conditional on participation. Second, we find little evidence of a
positive relationship between commercialization and nutritional status. As
countries and international agencies prioritize the importance of nutrition
sensitive agriculture, better understanding of the transmission channels between
crop choices and nutritional outcomes should remain a research priority.
PMID- 28413251
TI - Food price seasonality in Africa: Measurement and extent.
AB - Everyone knows about seasonality. But what exactly do we know? This study
systematically measures seasonal price gaps at 193 markets for 13 food
commodities in seven African countries. It shows that the commonly used dummy
variable or moving average deviation methods to estimate the seasonal gap can
yield substantial upward bias. This can be partially circumvented using
trigonometric and sawtooth models, which are more parsimonious. Among staple
crops, seasonality is highest for maize (33 percent on average) and lowest for
rice (161/2 percent). This is two and a half to three times larger than in the
international reference markets. Seasonality varies substantially across market
places but maize is the only crop in which there are important systematic country
effects. Malawi, where maize is the main staple, emerges as exhibiting the most
acute seasonal differences. Reaching the Sustainable Development Goal of Zero
Hunger requires renewed policy attention to seasonality in food prices and
consumption.
PMID- 28413252
TI - Labor productivity and employment gaps in Sub-Saharan Africa.
AB - Drawing on a new set of nationally representative, internationally comparable
household surveys, this paper provides an overview of key features of structural
transformation - labor allocation and labor productivity - in four African
economies. New, micro-based measures of sector labor allocation and cross-sector
productivity differentials describe the incentives households face when
allocating their labor. These measures are similar to national accounts-based
measures that are typically used to characterize structural change. However,
because agricultural workers supply far fewer hours of labor per year than do
workers in other sectors in all of the countries analyzed, productivity gaps
shrink by half, on average, when expressed on a per-hour basis. Underlying the
productivity gaps that are prominently reflected in national accounts data are
large employment gaps, which call into question the productivity gains that
laborers can achieve through structural transformation. Furthermore,
agriculture's continued relevance to structural change in Sub-Saharan Africa is
highlighted by the strong linkages observed between rural non-farm activities and
primary agricultural production.
PMID- 28413253
TI - Are African households (not) leaving agriculture? Patterns of households' income
sources in rural Sub-Saharan Africa.
AB - This paper uses comparable income aggregates from 41 national household surveys
from 22 countries to explore the patterns of income generation among rural
households in Sub-Saharan Africa, and to compare household income strategies in
Sub-Saharan Africa with those in other regions. The paper seeks to understand how
geography drives these strategies, focusing on the role of agricultural potential
and distance to urban areas. Specialization in on-farm activities continues to be
the norm in rural Africa, practiced by 52 percent of households (as opposed to 21
percent of households in other regions). Regardless of distance and integration
in the urban context, when agro-climatic conditions are favorable, farming
remains the occupation of choice for most households in the African countries for
which the study has geographically explicit information. However, the paper finds
no evidence that African households are on a different trajectory than households
in other regions in terms of transitioning to non-agricultural based income
strategies.
PMID- 28413254
TI - Non-farm entrepreneurship in rural sub-Saharan Africa: New empirical evidence.
AB - We report on the prevalence and patterns of non-farm enterprises in six sub
Saharan African countries, and study their performance in terms of labor
productivity, survival and exit, using the World Bank's Living Standards
Measurement Study - Integrated Surveys on Agriculture (LSMS-ISA). Rural
households operate enterprises due to both push and pull factors and tend to do
so predominantly in easy-to-enter activities, such as sales and trade, rather
than in activities that require higher starting costs, such as transport
services, or educational investment, such as professional services. Labor
productivity differs widely: rural and female-headed enterprises, those located
further away from population centers, and businesses that operate intermittently
have lower levels of labor productivity compared to urban and male-owned
enterprises, or enterprises that operate throughout the year. Finally, rural
enterprises exit the market primarily due to a lack of profitability or finance,
and due to idiosyncratic shocks.
PMID- 28413255
TI - Scalar and vector self-energies of heavy baryons in nuclear medium.
AB - The in-medium sum rules are employed to calculate the shifts in the mass and
residue as well as the scalar and vector self-energies of the heavy [Formula: see
text] and [Formula: see text] baryons, with Q being b or c quark. The maximum
shift in mass due to nuclear matter belongs to the [Formula: see text] baryon and
it is found to be [Formula: see text]. In the case of residue, it is obtained
that the residue of [Formula: see text] baryon is maximally affected by the
nuclear medium with the shift [Formula: see text]. The scalar and vector self
energies are found to be [Formula: see text], [Formula: see text], [Formula: see
text], [Formula: see text], [Formula: see text], [Formula: see text] and
[Formula: see text], [Formula: see text], [Formula: see text], [Formula: see
text], [Formula: see text] and [Formula: see text].
PMID- 28413256
TI - Dynamics of Postcombustion CO2 Capture Plants: Modeling, Validation, and Case
Study.
AB - The capture of CO2 from power plant flue gases provides an opportunity to
mitigate emissions that are harmful to the global climate. While the process of
CO2 capture using an aqueous amine solution is well-known from experience in
other technical sectors (e.g., acid gas removal in the gas processing industry),
its operation combined with a power plant still needs investigation because in
this case, the interaction with power plants that are increasingly operated
dynamically poses control challenges. This article presents the dynamic modeling
of CO2 capture plants followed by a detailed validation using transient
measurements recorded from the pilot plant operated at the Maasvlakte power
station in the Netherlands. The model predictions are in good agreement with the
experimental data related to the transient changes of the main process variables
such as flow rate, CO2 concentrations, temperatures, and solvent loading. The
validated model was used to study the effects of fast power plant transients on
the capture plant operation. A relevant result of this work is that an integrated
CO2 capture plant might enable more dynamic operation of retrofitted fossil fuel
power plants because the large amount of steam needed by the capture process can
be diverted rapidly to and from the power plant.
PMID- 28413257
TI - Tuning and Locking the Localized Surface Plasmon Resonances of CuS (Covellite)
Nanocrystals by an Amorphous CuPd x S Shell.
AB - We demonstrate the stabilization of the localized surface plasmon resonance
(LSPR) in a semiconductor-based core-shell heterostructure made of a plasmonic
CuS core embedded in an amorphous-like alloyed CuPd x S shell. This
heterostructure is prepared by reacting the as-synthesized CuS nanocrystals (NCs)
with Pd2+ cations at room temperature in the presence of an electron donor
(ascorbic acid). The reaction starts from the surface of the CuS NCs and proceeds
toward the center, causing reorganization of the initial lattice and
amorphization of the covellite structure. According to density functional
calculations, Pd atoms are preferentially accommodated between the bilayer formed
by the S-S covalent bonds, which are therefore broken, and this can be understood
as the first step leading to amorphization of the particles upon insertion of the
Pd2+ ions. The position and intensity in near-infrared LSPRs can be tuned by
altering the thickness of the shell and are in agreement with the theoretical
optical simulation based on the Mie-Gans theory and Drude model. Compared to the
starting CuS NCs, the amorphous CuPd x S shell in the core-shell nanoparticles
makes their plasmonic response less sensitive to a harsh oxidation environment
(generated, for example, by the presence of I2).
PMID- 28413258
TI - Fluorinated polyurethane scaffolds for 19F magnetic resonance imaging.
AB - Polymers are increasingly employed in implant materials. To reduce the incidence
of complications, which in the case of vascular grafts include incorrect
placement and restenosis, materials are needed which allow for image-guided
implantation, as well as for accurate and efficient postoperative implant
imaging. We here describe amorphous fluorinated polymers based on thermoplastic
polyurethane (19F-TPU), and show that are useful starting materials for
developing tissue-engineered vascular grafts which can be detected using 19F MRI.
PMID- 28413259
TI - Materials Genome in Action: Identifying the Performance Limits of Physical
Hydrogen Storage.
AB - The Materials Genome is in action: the molecular codes for millions of materials
have been sequenced, predictive models have been developed, and now the challenge
of hydrogen storage is targeted. Renewably generated hydrogen is an attractive
transportation fuel with zero carbon emissions, but its storage remains a
significant challenge. Nanoporous adsorbents have shown promising physical
adsorption of hydrogen approaching targeted capacities, but the scope of studies
has remained limited. Here the Nanoporous Materials Genome, containing over 850
000 materials, is analyzed with a variety of computational tools to explore the
limits of hydrogen storage. Optimal features that maximize net capacity at room
temperature include pore sizes of around 6 A and void fractions of 0.1, while at
cryogenic temperatures pore sizes of 10 A and void fractions of 0.5 are optimal.
Our top candidates are found to be commercially attractive as "cryo-adsorbents",
with promising storage capacities at 77 K and 100 bar with 30% enhancement to 40
g/L, a promising alternative to liquefaction at 20 K and compression at 700 bar.
PMID- 28413260
TI - Missing Linkers: An Alternative Pathway to UiO-66 Electronic Structure
Engineering.
AB - UiO-66 is a promising metal-organic framework for photocatalytic applications.
However, the ligand-to-metal charge transfer of an excited electron is
inefficient in the pristine material. Herein, we assess the influence of missing
linker defects on the electronic structure of UiO-66 and discuss their ability to
improve ligand-to-metal charge transfer. Using a new defect classification
system, which is transparent and easily extendable, we identify the most
promising photocatalysts by considering both relative stability and electronic
structure. We find that the properties of UiO-66 defect structures largely depend
on the coordination of the constituent nodes and that the nodes with the
strongest local distortions alter the electronic structure most. Defects hence
provide an alternative pathway to tune UiO-66 for photocatalytic purposes,
besides linker modification and node metal substitution. In addition, the
decomposition of MOF properties into node- and linker-based behavior is more
generally valid, so we propose orthogonal electronic structure tuning as a
paradigm in MOF design.
PMID- 28413261
TI - Sculpting Silica Colloids by Etching Particles with Nonuniform Compositions.
AB - We present the synthesis of new shapes of colloidal silica particles by
manipulating their chemical composition and subsequent etching. Segments of
silica rods, prepared by the ammonia catalyzed hydrolysis and condensation of
tetraethylorthosilicate (TEOS) from polyvinylpyrrolidone loaded water droplets,
were grown under different conditions. Upon decreasing temperature, delaying
ethanol addition, or increasing monomer concentration, the rate of dissolution of
the silica segment subsequently formed decreased. A watery solution of NaOH (~mM)
selectively etched these segments. Further tuning the conditions resulted in rod
cone or cone-cone shapes. Deliberately modulating the composition along the
particle's length by delayed addition of (3-aminopropyl)-triethoxysilane (APTES)
also allowed us to change the composition stepwise. The faster etching of this
coupling agent in neutral conditions or HF afforded an even larger variety of
particle morphologies while in addition changing the chemical functionality. A
comparable step in composition was applied to silica spheres. Biamine functional
groups used in a similar way as APTES caused a charge inversion during the
growth, causing dumbbells and higher order aggregates to form. These particles
etched more slowly at the neck, resulting in a biconcave silica ring sandwiched
between two silica spheres, which could be separated by specifically etching the
functionalized layer using HF.
PMID- 28413263
TI - Intensified Microwave-Assisted N-Acylation Procedure - Synthesis and Activity
Evaluation of TRPC3 Channel Agonists with a 1,3-Dihydro-2H-benzo[d]imidazol-2-one
Core.
AB - Upon controlled microwave heating and using cyanuric chloride as a coupling
reagent, an efficient amidation procedure for the synthesis of 1,3-dihydro-2H
benzo[d]imidazol-2-one-based agonists of TRPC3/6 ion channels has been developed.
Compared to the few conventional protocols, a drastic reduction in processing
time from ca. 2 days down to 10 minutes was achieved accompanied by significantly
improved product yields. The robustness of the method was confirmed by 18
additional examples including aromatic, aliphatic, and heterocyclic amines and
acids. The obtained agonists were screened for biological activity at 1 MUM
concentration and few structure-activity relations have been established.
PMID- 28413264
TI - Climate Variability and Inter-Provincial Migration in South America, 1970-2011.
AB - We examine the effect of climate variability on human migration in South America.
Our analyses draw on over 21 million observations of adults aged 15-40 from 25
censuses conducted in eight South American countries. Addressing limitations
associated with methodological diversity among prior studies, we apply a common
analytic approach and uniform definitions of migration and climate across all
countries. We estimate the effects of climate variability on migration overall
and also investigate heterogeneity across sex, age, and socioeconomic groups,
across countries, and across historical climate conditions. We also disaggregate
migration by the rural/urban status of destination. We find that exposure to
monthly temperature shocks has the most consistent effects on migration relative
to monthly rainfall shocks and gradual changes in climate over multi-year
periods. We also find evidence of heterogeneity across demographic groups and
countries. Analyses that disaggregate migration by the rural/urban status of
destination suggest that much of the climate-related inter-province migration is
directed toward urban areas. Overall, our results underscore the complexity of
environment-migration linkages and challenge simplistic narratives that envision
a linear and monolithic migratory response to changing climates.
PMID- 28413265
TI - Zinc toxicity stimulates microbial production of extracellular polymers in a
copiotrophic acid soil.
AB - The production of extracellular polymeric substances (EPS) is crucial for biofilm
structure, microbial nutrition and proximal stability of habitat in a variety of
environments. However, the production patterns of microbial EPS in soils as
affected by heavy metal contamination remain uncertain. Here we investigate the
extracellular response of the native microbial biomass in a grassland soil
treated with refined glycerol or crude unrefined biodiesel co-product (BCP) with
and without ZnCl2. We extracted microbial EPS and more readily soluble microbial
products (SMP), and quantified total polysaccharide, uronic acid, and protein
content in these respective extracts. Organic addition, especially BCP,
significantly stimulated the production of EPS-polysaccharide and protein but had
no impact on EPS-uronic acids, while in the SMP-fraction, polysaccharides and
uronic acids were both significantly increased. In response to the inclusion of
Zn2+, both EPS- and SMP-polysaccharides increased. This implies firstly that a
tolerance mechanism of soil microorganisms against Zn2+ toxicity exists through
the stimulation of SMP and EPS production, and secondly that co-products of
biofuel industries may have value-added use in bioremediation efforts to support
in-situ production of microbial biopolymers. Microbial films and mobile polymers
are likely to impact a range of soil properties. The recent focus on EPS research
in soils is anticipated to help contribute an improved understanding of biofilm
dynamics in other complex systems - such as continuously operated bioreactors.
PMID- 28413262
TI - Polymeric Materials for Gene Delivery and DNA Vaccination.
AB - Gene delivery holds great potential for the treatment of many different diseases.
Vaccination with DNA holds particular promise, and may provide a solution to many
technical challenges that hinder traditional vaccine systems including rapid
development and production and induction of robust cell-mediated immune
responses. However, few candidate DNA vaccines have progressed past preclinical
development and none have been approved for human use. This Review focuses on the
recent progress and challenges facing materials design for nonviral DNA vaccine
drug delivery systems. In particular, we highlight work on new polymeric
materials and their effects on protective immune activation, gene delivery, and
current efforts to optimize polymeric delivery systems for DNA vaccination.
PMID- 28413266
TI - Not just a separate consent for anesthesia!
PMID- 28413267
TI - Vasopressors: Do they have any role in hemorrhagic shock?
AB - The priority in the management of patients with traumatic hemorrhagic shock is to
control the bleeding with simultaneous volume resuscitation to maintain adequate
tissue perfusion. Fluid replacement remains the mainstay of initial resuscitation
in hemorrhagic shock. Traditionally, vasopressors are contraindicated in the
early management of hemorrhagic shock due to their deleterious consequences,
although vasopressors may have a role in resuscitation when vasoplegic shock
ensues and blood pressure cannot be maintained by fluids alone. Use of
vasopressors is not recommended according to the Advanced Trauma Life SupportR
management principles. The role of vasopressors remains controversial with no
clear guidelines on the timing, type, and dose of these drugs in hemorrhagic
shock. Among vasopressors, norepinephrine and vasopressin have been used in the
majority of the trials, although not many studies compare the effect of these two
on long-term survival in trauma patients. This article reviews the
pathophysiology of hemorrhagic shock, adverse effects of fluid resuscitation, and
the various experimental and clinical studies on the use of vasopressors in the
early phase of resuscitation in hemorrhagic shock.
PMID- 28413268
TI - Novel propofol derivatives and implications for anesthesia practice.
AB - Propofol (2,6-diisopropylphenol) is the most commonly used intravenous agent for
induction of anesthesia. It is also used for maintenance of anesthesia and
sedation in both Intensive Care Units and outpatient procedural settings. Its
success in the clinical setting has been a result of its rapid onset, short
duration of action, and minimal side effects despite disadvantages associated
with its oil emulsion formulation. Early attempts to alter the standard emulsion
or to develop new formulations with cyclodextrins and micelles to resolve issues
with pain upon injection, the need for antimicrobial agents, and possible
hyperlipidemia have mostly failed. With these challenges in the foreground,
attention has now shifted to the use of more prodrugs and exogenous alternatives,
the success of which is yet to be determined. These new agents must offer
significant clinical advantages over the well-entrenched, generic propofol oil
emulsion to justify higher costs and to be well received in the increasingly cost
conscious healthcare marketplace.
PMID- 28413270
TI - The effect of perioperative esmolol on early postoperative pain: A systematic
review and meta-analysis.
AB - Esmolol has been shown to improve postoperative pain and reduce opioid
requirements. The aim of this systematic review was to evaluate the effect of
perioperative esmolol as an adjunct on early postoperative pain intensity,
recovery profile, and anesthetic requirement. Databases were searched for
randomized placebo-controlled trials evaluating the effects of esmolol during
general anesthesia. Primary outcomes were related to early postoperative pain
whereas secondary outcomes were related to emergence time, postoperative nausea
and vomiting, and intraoperative anesthetic requirement. Nineteen trials were
identified involving 936 patients (esmolol = 470, placebo = 466). In esmolol
group, numeric pain scores at rest in the immediate postoperative period were
reduced by 1.16 (95% confidence interval [CI]: 1.97-0.35, I2 = 96.7%) out of 10.
Opioid consumption was also decreased in the postanesthesia care unit compared
with placebo, mean difference of 5.1 mg (95% CI: 7.0-3.2, I2 = 96.9%) morphine IV
equivalents; a 69% reduction in opioid rescue dosing was noted (odds ratio [OR]:
0.31, 95% CI: 0.16-0.80, I2 = 0.0%). A 61% reduction in postoperative nausea and
vomiting was also evident (OR: 0.39, 95% CI: 0.20-0.75, I2 = 60.7%). A reduction
in propofol induction dose was noted in the esmolol group (mean difference: -0.53
mg/kg, 95% CI: -0.63--0.44, I2 = 0.0%). A decrease in end-tidal desflurane
equivalent (mean difference: 1.70%, 95% CI: -2.39--1.02, I2 = 92.0%) and
intraoperative opioid usage (fentanyl equivalent, mean difference: 440 MUg, 95%
CI: -637--244, I2 = 99.6%) was observed in esmolol group. Esmolol had no effect
on the emergence time. Perioperative esmolol as an adjunct may reduce
postoperative pain intensity, opioid consumption, and postoperative nausea
vomiting. Given the heterogeneity, larger clinical trials are warranted to
confirm these findings.
PMID- 28413269
TI - Localization of epidural space: A review of available technologies.
AB - Although epidural analgesia is widely used for pain relief, it is associated with
a significant failure rate. Loss of resistance technique, tactile feedback from
the needle, and surface landmarks are traditionally used to guide the epidural
needle tip into the epidural space (EDS). The aim of this narrative review is to
critically appraise new and emerging technologies for identification of EDS and
their potential role in the future. The PubMed, Cochrane Central Register of
Controlled Clinical Studies, and Web of Science databases were searched using
predecided search strategies, yielding 1048 results. After careful review of
abstracts and full texts, 42 articles were selected to be included. Newer
techniques for localization of EDS can be broadly classified into techniques that
(1) guide the needle to the EDS, (2) identify needle entry into the EDS, and (3)
confirm catheter location in EDS. An ideal method should be easy to learn and
perform, easily reproducible with high sensitivity and specificity, identifies
inadvertent intrathecal and intravascular catheter placements with ease, feasible
in perioperative setting and have a cost-benefit advantage. Though none of them
in their current stages of development qualify as an ideal method, many show
tremendous potential. Some techniques are useful in patients with difficult
spinal anatomy and infants, and thus are complementary to traditional methods. In
addition to improving the existing technology, future research should aim at
proving the superiority of these techniques over traditional methods,
specifically regarding successful EDS localization, better safety profile, and a
favorable cost-benefit ratio.
PMID- 28413271
TI - ASSIST - Patient satisfaction survey in postoperative pain management from Indian
subcontinent.
AB - INTRODUCTION: To compare pain scores at rest and ambulation and to assess patient
satisfaction between the different modalities of pain management at different
time points after surgery. SETTINGS AND DESIGN: The ASSIST (Patient Satisfaction
Survey: Pain Management) was an investigator-initiated, prospective, multicenter
survey conducted among 1046 postoperative patients from India. MATERIAL AND
METHODS: Pain scores, patient's and caregiver's satisfaction toward postoperative
pain treatment, and overall pain management at the hospital were captured at
three different time points through a specially designed questionnaire. The
survey assessed if the presence of acute pain services (APSs) leads to better
pain scores and patient satisfaction scores. STATISTICAL ANALYSIS: One-way ANOVA
was used to evaluate the statistical significance between different modalities of
pain management, and paired t-test was used to compare pain and patient
satisfaction scores between the APS and non-APS groups. RESULTS: The results
indicated that about 88.4% of patients reported postoperative pain during the
first 24 h after surgery. The mean pain score at rest on a scale of 1-10 was 2.3
+/- 1.8 during the first 24 h after surgery and 1.1 +/- 1.5 at 72 h; the patient
satisfaction was 7.9/10. Significant pain relief from all pain treatment was
reported by patients in the non-APS group (81.6%) compared with those in the APS
(77.8%) group (P < 0.0016). CONCLUSION: This investigator-initiated survey from
the Indian subcontinent demonstrates that current standards of care in
postoperative pain management remain suboptimal and that APS service, wherever it
exists, is yet to reach its full potential.
PMID- 28413272
TI - An analysis of perioperative adverse neurological events associated with
anesthetic management at a Tertiary Care Center of a developing country.
AB - BACKGROUND AND AIMS: Existing literature on neurological complications related to
anesthesia is reported from affluent countries but the trends may vary in less
affluent countries. MATERIAL AND METHODS: The objective was to find the
associated factors contributing to neurological adverse events occurring within
48 h of anesthesia and surgery. The existing departmental morbidity and mortality
database was reviewed from 1992 to 2012 for major adverse neurological events. A
standardized methodology was used in reviewing and classifying the data. All
adverse events were predefined and categorized before filling the form into the
following headers; meningitis, cord/plexus/peripheral nerve injury, stroke,
paraparesis/paraplegia/quadriparesis/or quadriplegia, new onset postoperative
seizures, postoperative vocal cord injury, and a miscellaneous group. RESULTS:
During this period, 195,031 patients underwent anesthesia and twenty-nine
patients had major neurological morbidity within 48 h (1:6700). There were three
cases of meningitis/meningism, eight cases of cord, plexus or peripheral nerve
injury, seven of stroke, four had new onset seizures, one had quadriparesis, five
had vocal cord, and one had cranial nerve palsy. Forty-one percent cases received
regional anesthesia alone or in combination with the general. In six cases,
anesthesia was considered solely responsible. Human error contributed to 93% of
these events. CONCLUSION: This data has helped in identifying areas of concern
and can serve as a reference for further audits in the region.
PMID- 28413273
TI - Intraoperative low tidal volume ventilation strategy has no benefits during
laparoscopic cholecystectomy.
AB - BACKGROUND AND AIMS: Benefits of intraoperative low tidal volume ventilation
during laparoscopic surgery are not conclusively proven, even though its
advantages were seen in other situations with intraoperative respiratory
compromise such as one-lung ventilation. The present study compared the efficacy
of intraoperative low tidal volume ventilatory strategy (6 ml/kg along with
positive end-expiratory pressure [PEEP] of 10 cmH2O) versus one with higher tidal
volume (10 ml/kg with no PEEP) on various clinical parameters and plasma levels
of interleukin (IL)-6 in patients undergoing laparoscopic cholecystectomy.
MATERIAL AND METHODS: A total of 58 adult patients with American Society of
Anesthesiologists physical status I or II, undergoing laparoscopic
cholecystectomy were randomized to receive the low or higher tidal volume
strategy as above (n = 29 each). The primary outcome measure was postoperative
PaO2. Systemic levels of IL-6 along with clinical indices of intraoperative gas
exchange, pulmonary mechanics, and hemodynamic consequences were measured as
secondary outcome measures. RESULTS: There was no statistically significant
difference in oxygenation; intraoperative dynamic compliance, peak airway
pressures, or hemodynamic parameters, or the IL-6 levels between the two groups
(P > 0.05). Low tidal volume strategy was associated with significantly higher
mean airway pressure, lower airway resistance, greater respiratory rates, and
albeit clinically similar, higher PaCO2and lower pH (P < 0.05). CONCLUSION:
Strategy using 6 ml/kg tidal volume along with 10 cmH2O of PEEP was not
associated with any significant improvement in gas exchange, hemodynamic
parameters, or systemic inflammatory response over ventilation with 10 ml/kg
volume without PEEP during laparoscopic cholecystectomy.
PMID- 28413274
TI - Evaluation of decision-to-delivery interval in emergency cesarean section: A 1
year prospective audit in a tertiary care hospital.
AB - BACKGROUND AND AIMS: The American College of Obstetricians and Gynecologists
(ACOG) committee on professional standards and the National Institute of Clinical
Excellence (NICE) guidelines suggest that decision-to-delivery interval (DDI) and
emergency cesarean section (CS) should not be more than 30 min, and a delay of
more than75 min in the presence of maternal or fetal compromise can lead to poor
outcome. This prospective 1-year study was conducted on emergency CS in a
tertiary care hospital to evaluate the DDI, factors affecting it and to analyze
their effects on maternal and neonatal outcome. MATERIAL AND METHODS: A
structured proforma was used to analyze the data from all women undergoing
emergency CS, during a 1-year period, included in Category 1 and 2 of NICE
guidelines for CS. RESULTS: A total of 453 emergency CSs were evaluated, with a
mean DDI of 36.3 +/- 17.2 min for Category 1 CS and 38.1 +/- 17.7 min for
Category 2 CS (P > 0.05). Only 42.4% emergency CSs confirmed to the 30 min DDI
while 57.6% had a DDI of more than 30 min. Reasons of delay were identified as a
delay in shifting the patient to operation theater (22.1%), anesthesia factors
(18.1%), and lack of resources or manpower (16.1%). Maternal complications
occurred in 15 (3.3%) patients with 3 (0.7%) nonsurvivors having a DDI of 91.0 +/
97.0 min as compared to survivors with a DDI of 36.8 +/- 15.7 min, P = 0.001.
There was no significant association between DDI and occurrence of neonatal
complications. CONCLUSION: Failure to meet the current recommendations was
associated with adverse maternal outcomes, but not with adverse neonatal outcome.
PMID- 28413275
TI - Comparison of trapezius squeeze test and jaw thrust as clinical indicators for
laryngeal mask airway insertion in spontaneously breathing children.
AB - BACKGROUND AND AIMS: It is not known whether trapezius squeeze test (TPZ) is a
better clinical test than jaw thrust (JT) to assess laryngeal mask airway (LMA)
insertion conditions in children under sevoflurane anesthesia. MATERIAL AND
METHODS: After the Institutional Ethics Committee approval and written informed
parental consent, 124 American Society of Anesthesiologists I and II children of
2-8 years of age undergoing minor surgical procedures were randomized into TPZ
and JT groups. The children were induced with 8% sevoflurane in oxygen at a fresh
gas flow of 4 L/min. TPZ or JT was performed after 1 min of start of sevoflurane
and then every 20 s till the test was negative, when end-tidal (ET) sevoflurane
concentration was noted. Classic LMA of requisite size was inserted by a blinded
anesthetist and conditions at the insertion of LMA, insertion time, and the
number of attempts of LMA insertion were recorded. RESULTS: The mean LMA
insertion time was significantly longer (P < 0.001) for TPZ (145 +/- 28.7 sec)
compared to JT group (111.8 +/- 31.0 sec). ET sevoflurane concentration at the
time of LMA insertion was comparable in the two groups. LMA insertion conditions
were similar in the two groups. There was no difference between the two groups
regarding total number of attempts of LMA insertion. Heart rate (HR) decreased in
both groups after LMA insertion (P < 0.001) but TPZ group had significantly lower
HR compared with the JT group up to 5 min after LMA insertion (P = 0.03).
CONCLUSION: Both JT and TPZ are equivalent clinical indicators in predicting the
optimal conditions of LMA insertion in spontaneously breathing children; however,
it takes a longer time to achieve a negative TPZ squeeze test.
PMID- 28413276
TI - Comparison between ketamine and hyoscine for the management of postoperative
catheter-related bladder discomfort: A randomized controlled double-blind study.
AB - BACKGROUND AND AIM: Postoperative catheter-related bladder discomfort (CRBD) can
be a distressing complication for patients in whom a urinary catheter was
inserted intraoperatively and is accompanied with patients' dissatisfaction. This
trial investigated the efficacy of hyoscine and ketamine on treatment of
postoperative CRBD in patients undergoing various surgeries. MATERIAL AND
METHODS: This was a prospective randomized, double-blind study, which included 60
American Society of Anesthesiologists Class I-II male patients undergoing
elective nonurological operations requiring intraoperative urinary
catheterization under general anesthesia after ethical approval and written
informed consent. Patients were allocated randomly into two groups: The hyoscine
group (H group) (n = 30) received 20 mg of hyoscine intravenously and ketamine
group (K group) (n = 30) received 0.25 mg/kg of ketamine intravenously
immediately after the occurrence of CRBD. The severity of CRBD was assessed at 0,
1, 2, and 4 h postoperatively. Adverse effects of hyoscine and ketamine were also
examined. Data were summarized using mean +/- standard deviation, and comparisons
between groups were done by unpaired t-test. For comparison of serial
measurements within each group, ANOVA was used. RESULTS: There was a significant
difference between the two groups in the severity of CRBD measured by visual
analog scale score only 30 min after drug administration where it was higher in
ketamine group (44.50 +/- 7.70) compared to hyoscine group (36.00 +/- 8.55) (P <
0.001), otherwise there was no significant difference at other time points
between the two groups, also there was a significant rise in heart rate in
hyoscine group but no significant difference in mean arterial pressure.
CONCLUSION: Intravenous hyoscine 20 mg is more effective in control of CRBD than
ketamine (0.25 mg/kg) in the first 30 min; later on they have the same effect.
PMID- 28413277
TI - Efficacy of dexmedetomidine with ropivacaine in supraclavicular brachial plexus
block for upper limb surgeries.
AB - BACKGROUND AND AIMS: The primary aim of this study was to evaluate the effect of
addition of dexmedetomidine on the duration of analgesia in patients undergoing
upper limb surgeries under supraclavicular brachial plexus block. MATERIAL AND
METHODS: Sixty patients of American Society of Anesthesiologists physical status
I/II/III undergoing elective upper limb surgeries under supraclavicular brachial
plexus block using nerve stimulator were randomized into two groups. Group A (n =
30) received 30 mL 0.5% ropivacaine and 1 mL normal saline, and Group B (n = 30)
received 30 mL 0.5% ropivacaine and 1 MUg/kg of dexmedetomidine. The primary
outcome was the duration of analgesia. Secondary outcomes included time to onset
and duration of sensory/motor blockade. STATISTICAL ANALYSIS: Results on
continuous measurements are presented as mean +/- standard deviation and compared
using Student's unpaired t-test. Results on categorical measurements are
presented in number (%) and compared using Chi-square test. RESULTS: Onset of
sensory and motor block in Group A (13.0 +/- 4.1 and 23.5 +/- 5.6 min) was slower
than those in Group B (9.5 +/- 5.8 and 15.6 +/- 6.3 min; P = 0.009 for sensory
and P < 0.001 for the motor block). Duration of sensory and motor block in Group
A (400.8 +/- 86.6 and 346.9 +/- 76.9 min) was shorter than those in Group B
(630.6 +/- 208.2 and 545.9 +/- 224.0 min; (P < 0.001). The duration of analgesia
in Group A (411.0 +/- 91.2 min) was shorter than that in Group B (805.7 +/- 205.9
min; P < 0.001). The incidence of bradycardia and hypotension was higher in Group
B than in Group A (P < 0.001). CONCLUSION: Perineural dexmedetomidine with
ropivacaine provides prolonged postoperative analgesia, hastens the onset of
sensory and motor block and prolongs the duration of the supraclavicular brachial
plexus block.
PMID- 28413278
TI - Work-related stress: A survey of Indian anesthesiologists.
AB - BACKGROUND AND AIMS: Work-related stress is common among medical caregivers and
concerns all perioperative care providers. Although anesthesiologists are known
to experience stress, there are limited Indian data addressing this issue. This
survey was conducted among Indian anesthesiologists to determine their awareness
about work stress and views regarding prevention programs. MATERIAL AND METHODS:
A survey questionnaire was distributed to delegates visiting the exhibits at the
national anesthesiology conference in 2011. The questionnaire had ten questions
on the work pattern, five on work-related stress, nine on opinion regarding the
need and willingness to participate in stress-related programs. RESULTS: There
were 1178 responders. Forty-three percent were faculty in medical institutions,
26% were residents and 25% were in free-lance practice. Ninety-one percent of
participants rated their stress as moderate-extreme. There was a significant
correlation between the amount of stress and working for more than 8 h (P <
0.001), handling high risk patients (P = 0.002), working on weekends (P = 0.002),
and carrying work back home (P < 0.001). Forty-one percent of respondents were
very satisfied professionally. Seventy-six percent of doctors agreed that the
questionnaire had made them think about work stress. Eighty-four percent of
participants felt the need for stress management programs and 69% expressed their
willingness to participate in the same. CONCLUSION: The majority of participants
rated their stress as moderate-extreme and was higher in anesthesiologists
working long hours, over the weekend and those handling high-risk patients. A
majority of participants felt the survey made them think about work-related
stress and expressed their willingness to participate in stress management
programs.
PMID- 28413279
TI - Comparing slow and rapid bolus of ephedrine in pregnant patients undergoing
planned cesarean section under spinal anesthesia.
AB - BACKGROUND AND AIMS: While ephedrine was the preferred drug for treating spinal
induced hypotension in pregnancy, its use has declined because of resultant fetal
acidosis. The objective of this randomized control trial was to compare the
effects of a slow and rapid bolus of ephedrine on fetal acidosis, maternal blood
pressure, and heart rate (HR) during cesarean section performed under spinal
anesthesia. MATERIAL AND METHODS: Eighty full-term parturients scheduled for
cesarean section under spinal anesthesia were randomly allocated into two groups.
While both groups received 6 mg of ephedrine to treat hypotension, Group R (n =
40) received it as a rapid intravenous bolus and Group S (n = 40) received it
slowly over 20 s with an infusion pump. The maternal vital parameters were
recorded until delivery of the baby using a video camera. Umbilical cord blood
was obtained using the three clamp method. Hemodynamic parameters, fetal
acidosis, total number of ephedrine bolus used, peak HR after the ephedrine
bolus, and occurrence of postoperative nausea and vomiting (PONV) were compared
between the groups. RESULTS: Mean increase in HR and blood pressure were
significantly higher in Group R than the Group S after the first ephedrine bolus.
Umbilical artery pH was significantly lower in Group R than in Group S (7.2 [6.8
7.3] vs. 7.3 [7.3-7.4], P < 0.01). A total number of ephedrine boluses were
comparable in the two groups. 35% of the patients had PONV in Group R, whereas
none had it in Group S (P < 0.01). CONCLUSION: Slow bolus of ephedrine is better
than rapid bolus to treat spinal-induced hypotension during cesarean section in
view of less fetal acidosis.
PMID- 28413280
TI - Comparison of sevoflurane and propofol for laryngeal mask airway insertion and
pressor response in patients undergoing gynecological procedures.
AB - BACKGROUND AND AIMS: A popular method of providing anesthesia for laryngeal mask
airway (LMA) insertion is with the use of propofol. However, bolus propofol has
been associated with adverse effects such as hypotension, apnea and pain on
injection. Hence, time is needed to search an alternative. We aimed to compare
the induction characteristics, ease of LMA insertion, hemodynamic changes and
complications with inhalation of 8% sevoflurane vital capacity breath and
propofol. MATERIAL AND METHODS: A prospective randomized study of 60 American
Society of Anesthesiologists' Grade I and II patients was conducted and
distributed among two groups with 30 each undergoing gynecological procedures
under general anesthesia. Group P received the injection propofol and Group S
received sevoflurane. At the end point of induction, the LMA insertion was
attempted. Scoring systems were used to grade the conditions for insertion of the
LMA. Induction, LMA insertion characteristics, hemodynamic changes, complications
were assessed. Data were recorded and analyzed. Comparison among the study groups
was done with unpaired t-test, Mann-Whitney test and Chi-square test. RESULTS:
Sevoflurane took a longer time for induction and for LMA insertion than propofol.
There was no statistically significant difference between the two groups, with
respect to LMA insertion characteristics, heart rate, mean arterial pressure. It
is concluded that sevoflurane is associated with good hemodynamic stability and
may prove useful incases where propofol is to be avoided. However, the ease of
insertion provided with propofol is better.
PMID- 28413281
TI - A comparative study of the effect of clonidine, fentanyl, and the combination of
both as adjuvant to intrathecal bupivacaine for postoperative analgesia in total
abdominal hysterectomy.
AB - BACKGROUND AND AIMS: The aim of this study was to evaluate the level of sensory
block, onset and duration of motor block, postoperative analgesia, and adverse
effects of combination of clonidine and fentanyl given intrathecally with
hyperbaric bupivacaine (HB). MATERIAL AND METHODS: Three hundred and twenty eight
patients were randomized into four groups. Group bupivacaine (group B) received
15 mg of HB; group bupivacaine clonidine (group BC) received 15 mg of HB plus 25
MUg clonidine; group bupivacaine fentanyl (group BF) received 15 mg of HB plus 25
MUg fentanyl and group bupivacaine clonidine fentanyl (group BCF) received 15 mg
of HB plus 25 MUg clonidine and 25 MUg fentanyl intrathecally. All groups were
evaluated for level of sensory block, onset and duration of motor block,
postoperative analgesia, VAS score, sedation score and adverse effects of study
drugs. All the data were analyzed using unpaired t-test. P < 0.05 was considered
significant. RESULTS: The level of sensory block, onset, and duration of motor
block were comparable in all groups. Total duration of analgesia was 407.3 +/- 20
min in group BCF compared to 242.1 +/- 2 min and 209.2 +/- 16 in groups BC and
BF, respectively. Lesser doses of rescue analgesic were required in group BCF.
The time interval from intrathecal injection to two-segment regression was
statistically significant in study groups. Only 2.4% patients showed mild
sedation in BCF group. CONCLUSION: We found that combination of intrathecal
clonidine and fentanyl along with bupivacaine increases the total duration of
analgesia without significant side effects.
PMID- 28413283
TI - Is it time to separate consent for anesthesia from consent for surgery?
PMID- 28413282
TI - Comparison of success of tracheal intubation using Macintosh laryngoscope
assisted Bonfils fiberscope and Truview video laryngoscope in simulated difficult
airway.
AB - BACKGROUND AND AIMS: Restriction of head and neck movements prevents the
alignment of the oral, pharyngeal, and laryngeal axes and increases the incidence
of difficult tracheal intubation in patients with cervical spine fractures. Video
laryngoscopes have gained an important role in the management of difficult
intubation, especially in situations with limited head and neck movements. This
study compares the success of intubation using Macintosh laryngoscope assisted
Bonfils(r) fiberscope (ML-BF) with TruviewPCD video laryngoscope (TV) in patients
with simulated restricted head and neck movements. MATERIAL AND METHODS: One
hundred and fifty-two patients satisfying the inclusion criteria were randomly
allocated to two groups of 76 each. Patients were made to lie supine on the table
without a pillow and a soft collar was used to restrict head and neck movements.
After a standardized premedication-induction sequence, tracheal intubation was
done either with ML-BF or TV. Success of intubation, time taken for successful
intubation, hemodynamic changes, airway trauma, and postoperative oropharyngeal
morbidity were noted. RESULTS: Intubation was successful in all the 76 patients
in direct laryngoscopy-Bonfils fiberscope group and 75 out of 76 patients in TV
group within the specified time (90 s). The median time taken for successful
intubation with TV and ML-BF were 44 (range 26-80) s and 49 (range 28-83) s,
respectively. Hemodynamic changes, airway trauma, and postoperative oropharyngeal
morbidity were similar in both groups. CONCLUSION: Both TV and ML-BF are equally
effective for successful tracheal intubation in patients with simulated
restricted head and neck movements. In cases of difficult laryngeal visualization
with routine Macintosh laryngoscope, Bonfils can be used as an adjunct to achieve
successful intubation in the same laryngoscopy attempt.
PMID- 28413284
TI - Combined mitral and aortic stenosis in parturient: Anesthesia management for
labor and delivery.
AB - Maternal heart disease complicates 0.2-3% of pregnancies. The optimal management
of the pregnant patient with cardiac disease depends on the co-operative efforts
of the obstetrician, the cardiologist and the anesthesiologist involved in
peripartum care. A comprehensive understanding of physiology of pregnancy and
pathophysiology of underlying cardiac disease is of primary importance in
provision of obstetric analgesia or anesthesia for these high-risk groups of
patients. We report a successful and uncomplicated use of epidural anesthesia for
labor and delivery in patient with combined aortic and mitral stenosis.
PMID- 28413286
TI - Transversus abdominis plane catheters for postoperative pain relief in pediatric
patients.
AB - Regional techniques provides excellent post operative pain relief in pediatric
patients. Transversus abdominis plane (TAP) block is a newer regional technique
available. Though there is emerging evidence proving the efficacy of TAP blocks,
there is limited literature on use of TAP catheters in pediatric patients. TAP
catheters were placed in two children following laparotomy with transverse
incisions and in both epidural was avoided, with good post operative pain relief.
Ultrasound guidance was used in one child, while in the other the catheter was
placed under direct vision after dissection of the plane between transversus
abdominis and internal oblique. Intermittent boluses of high volumes of local
anesthetic (0.6-0.7 ml/kg) were used through the TAP catheter, ensuring that the
maximum permissible level of bupivacaine was not exceeded. In adults, continuous
abdominal catheters have found a place for post-operative pain management, when
epidural analgesia is contraindicated. At present, the use of TAP catheters by
pediatric anesthesiologists is limited, though there exists diverse clinical
scenarios when these catheters may be of benefit. Contraindication of neuraxial
blockade and septic patients are the two scenarios we have reported. In
conclusion, TAP catheters are effective analgesia technique for laparotomies with
transverse incision in pediatric patients.
PMID- 28413285
TI - Disseminated intravascular and intracardiac thrombosis after cardiopulmonary
bypass.
AB - Massive intracardiac and intravascular thrombosis is a rare complication
following cardiopulmonary bypass (CPB). Most of the cases of the disseminated
thrombosis have been reported in patients undergoing complex cardiac surgeries
and those receiving antifibrinolytic agents during CPB. We report the occurrence
of disseminated intravascular and intracardiac thrombosis after CPB in a patient
undergoing mitral valve replacement in which no antifibrinolytic agent was used.
The possible pathophysiology and management of the patient is discussed.
PMID- 28413287
TI - De-addiction: A new risk for anesthesia.
PMID- 28413288
TI - Obtaining external jugular venous access in the prone-positioned patient.
PMID- 28413289
TI - Intra-operative mechanical ventilation in amebic liver abscess surgery: Another
paradigm.
PMID- 28413290
TI - Unusual case of endotracheal tube obstruction by caseous necrotic material.
PMID- 28413291
TI - Green urine: A cause for concern?
PMID- 28413292
TI - LMA Proseal for the surgical procedures in prone positioning.
PMID- 28413293
TI - In response to: Comparison of paravertebral and interpleural block in patients
undergoing modified radical mastectomy.
PMID- 28413294
TI - Response to the letter for the article: Use of transversus abdominis plane block
as an anesthetic technique in a high-risk patient for abdominal wall surgery.
PMID- 28413295
TI - Emergency airway management of intratracheal tumor in a patient with respiratory
distress.
PMID- 28413296
TI - Immediate onset of postdural puncture headache after spinal anesthesia.
PMID- 28413297
TI - Ketamine-induced QTc interval prolongation.
PMID- 28413298
TI - Anorectal Malformation: Issues Beyond Definitive Surgery.
PMID- 28413299
TI - Congenital Pouch Colon.
AB - Congenital pouch colon (CPC) is an unusual abnormality in which a pouch-like
dilatation of a shortened colon is associated with an anorectal malformation. It
is categorized into four subtypes (Types I-IV) based on the length of normal
colon proximal to the colonic pouch. In males, the pouch usually terminates in a
colovesical fistula just proximal to the bladder neck. In girls, the terminal
fistula opens either into the urethra or in the vestibule, close to the urethral
opening. Girls usually have a double vagina with a wide inter-vaginal bridge, a
monocornuate uterus on each side, and urinary incontinence due to a widely open
bladder neck. Associated major malformations are uncommon with CPC but sometimes,
especially in reports from outside India, major abnormalities are present
suggesting an early, severe error in embryogenesis. The more severe Types I/II
CPC can usually be diagnosed by a large gas shadow or air-fluid level on X-Ray
abdomen. For all subtypes of CPC, it is preferable to preserve a segment of the
pouch by fashioning a narrow colonic tube for pull-through, the technique known
as coloplasty or tubular colorraphy. Girls need additional management of the
genitourinary abnormalities. Postoperatively, fecal continence levels are usually
poor, especially with Types I/II CPC.
PMID- 28413300
TI - Anorectal Agenesis with Rectovaginal Fistula: A Rare/Regional Variant.
AB - AIMS AND OBJECTIVES: The anatomical types of female anorectal malformation (ARM)
are complex and include several rare and regional variants. The aim of this
report is to highlight the diagnosis and management of cases of anorectal
agenesis with rectovaginal fistula (RVF). MATERIALS AND METHODS: This is a
retrospective chart review of cases of RVF who underwent definitive surgery
between November 2000 and September 2016 in a single institution. RESULTS: Of the
244 female patients with anorectal anomalies treated in our institution over a 16
year period, there were 15 cases of RVF with anorectal agenesis giving it an
incidence of 6%. All cases of RVF with anorectal agenesis presented with absence
of anal opening, varying degree of abdominal distension, and history of passage
of fecal matter per vaginum. The mean age of presentation was 3 months (newborn
to 1 year). Sigmoid colostomy was done in 13 cases. Distal colostogram
demonstrated high RVF which was further confirmed by examination under anesthesia
(EUA) and endoscopy before definitive surgery. With the posterior sagittal
approach, division of the RVF and anorectoplasty was possible in 14 cases;
however, one patient required an abdominal mobilization of the colon for pull
through due to a very short distal bowel segment. During a mean postoperative
follow-up of 5 years, cosmetic and functional results were satisfactory.
CONCLUSION: RVF with anorectal agenesis is a rare/regional variant of female
ARMs. Clinical examination along with distal colostogram, EUA, and endoscopy
clinches the diagnosis. Anorectal reconstruction by posterior sagittal
anorectoplasty results in a satisfactory outcome.
PMID- 28413301
TI - Anorectal Malformations in Males: Pros and Cons of Neonatal versus Staged
Reconstruction for High and Intermediate Varieties.
AB - BACKGROUND: High and intermediate types of anorectal malformations (ARMs) in male
neonates may be managed either by primary neonatal reconstruction without
colostomy cover or by traditional policy of staged reconstruction after neonatal
colostomy. Posterior sagittal anorectoplasty (PSARP) is the current widely
practiced reconstructive technique with varied results. AIM: To assess our
functional results of PSARP without colostomy in male neonates with high and
intermediate ARMs compared to 3-stage (neonatal colostomy - PSARP - colostomy
closure) methodology in a high volume tertiary care institution of a developing
country. PATIENTS AND METHODS: The number of colostomies performed for male
high/intermediate anomalies and the number of babies who completed 3-stage
reconstruction during a 10-year period is analyzed. The outcome of primary
neonatal PSARPs during the same period was analyzed. Eighty primary PSARPs were
compared to 81 staged reconstructions for outcome analysis, using Kelly score.
RESULTS: A total of 453 colostomies were performed, but only 253 of them
completed all stages of reconstruction (52%). Good continence was achieved in 45%
of cases of primary PSARP versus 26% in 3-staged surgery. CONCLUSIONS: Primary
PSARP in neonatal period without colostomy is a good option for high and
intermediate ARMs in males if the treating surgeon is reasonably skilled in
neonatal surgery and PSARP procedures.
PMID- 28413302
TI - Primary Definitive Procedure versus Conventional Three-staged Procedure for the
Management of Low-type Anorectal Malformation in Females: A Randomized Controlled
Trial.
AB - INTRODUCTION: Females with Krickenbeck low-type anorectal malformations -
vestibular fistula (VF) and perineal fistula (PF) - are managed either by a
primary definitive or conventional three-staged approach. Ultimate outcome in
these children may be affected by wound dehiscence leading to healing by
fibrosis. Most of the literature favors one approach over other based on
retrospective analysis of their outcomes. Whether a statistically significant
difference in wound dehiscence rates between these approaches exists needed to be
seen. MATERIALS AND METHODS: A randomized controlled trial for girls <14 years
with VF or PF was done. Random tables were used to randomize 33 children to Group
I (primary procedure) and 31 to Group II (three-staged procedure). Statistical
analysis was done for significance of difference (P < 0.05) in the primary
outcome (wound dehiscence) and secondary outcomes (immediate and early
postoperative complications). RESULTS: Of the 64 children randomized, 54 (84%)
had VF. Both groups were comparable in demography, clinical profile and age at
surgery. The incidence of wound dehiscence (39.4% vs. 18.2%; P = 0.04), immediate
postoperative complications (51.5% vs. 12.9%; P = 0.001), and early postoperative
complications (42.4% vs. 12.9%; P = 0.01) was significantly higher in Group I as
compared to Group II. Six of 13 children (46.2%) with dehiscence in Group I
required a diverting colostomy to be made. CONCLUSIONS: Females with VF or PF
undergoing primary definitive procedure have a significantly higher incidence of
wound dehiscence (P = 0.04), immediate (P = 0.001) and early postoperative
complications (P = 0.01).
PMID- 28413303
TI - Role of Interferential Therapy in Children with Fecal Incontinence Postanorectal
Malformation Surgeries.
AB - BACKGROUND: Anorectal malformation (ARM) is one of the most common pediatric
surgical problems dealt in day-to-day practice. Although the outcome of surgery
has improved a great deal over the last three decades fecal incontinence (FI) is
still a common long-term morbidity that affects the quality of life of these
patients. Bowel wash (BW) program with pelvic floor exercise are standard care of
management for these patients. This study was undertaken to assess the role of
interferential therapy (IFT) along with BW compared to BW alone in the management
of FI. METHODOLOGY: Twenty-four children more than 2-year-old age previously
operated for malformation and having FI with Kelly score <4 were recruited and
assigned to one of the two groups. One group was given standard BW regimen and
the other BW with IFT for 3 months. Posttherapy Kelly scoring was done, and the
results were compared. RESULTS: IFT with BW provided no added advantage over BW
alone for the treatment of FI in patients of ARMs. CONCLUSION: The time-tested
modality of BW is the cornerstone in the management of FI.
PMID- 28413304
TI - Simultaneous Single-staged Repair of Anorectal Malformation with
Tracheoesophageal Fistula: Lessons Learned.
AB - INTRODUCTION: Anorectal malformation (ARM) associated esophageal atresia (EA)
with tracheoesophageal fistula (TEF) spawns special therapeutic propositions. The
outcome of these patients banks on numerous factors. We performed this study with
an aim to compare the outcome of single-staged simultaneous primary repair of
both anomalies versus staged repair of these disorders. MATERIALS AND METHODS:
Retrospective review of cases with ARM and associated EA with TEF managed over a
period of 5 years from July 2010 to June 2015 after ethical approval was
undertaken. Patients were split into two groups based on whether they underwent
staged repair (Group A) or single-staged simultaneous primary repair of ARM with
TEF (Group B). Patient's records were analyzed for demography, weight,
gestational age, associated anomaly, preoperative and postoperative sepsis screen
results, early and late postoperative complications (at least up to 1 year of
age). Patient's Kelly score for continence at the age of 3 years or more was
compared. OBSERVATION: A total of 28 were included in the study. Among these, 17
were managed with staged procedure for ARM (Group A), whereas 11 underwent
simultaneous single-stage repair of ARM with TEF (Group B). No difference in
continence score was observed in outcome between the two groups (P = 0.96).
Overall mortality in Group A at 1-year follow-up was 52.9% and in Group B was
43.4%. CONCLUSION: The simultaneous single-staged primary repairs result in
better long-term outcome in our setup.
PMID- 28413305
TI - Solitary Functioning Kidney in High Anorectal Malformation.
AB - AIM: A solitary functioning renal unit in high anorectal malformation may harbor
anomalies in the upper/lower urinary tract that further compromise renal function
and accelerate hyperfiltration injury. We aimed to analyze the clinical course,
management, and outcome of children with a solitary renal unit and high anorectal
malformation. MATERIALS AND METHODS: A cohort of solitary renal units in
anorectal malformation managed between 2000 and 2015 with a defined protocol at a
pediatric nephro-urology clinic are included in the study. Investigations and
management were individualized according to issues in the agenetic/dysplastic
unit, solitary functioning unit, or bladder-urethra. Clinical details,
management, and outcome were analyzed. RESULTS: Of 53 cases of high anorectal
malformation with urologic anomalies, 17 (32%) had single kidneys. Majority
(10/17, 59%) had another complicating urinary tract anomaly, four being uremic at
presentation. Nearly half had multiple urinary infections including epididymo
orchitis unrelated to the rectourinary fistula and warranted additional stoma
(bowel/urinary) or other urinary tract surgery. At a mean follow-up of 70 months,
majority (14/17, 82%) have a preserved solitary renoureteric unit while the
remaining three await renal replacement therapy. CONCLUSION: Solitary functioning
renal units associated with high anorectal malformation in children need
meticulous investigation and surveillance to facilitate renal preservation. The
implications of the associated rectourinary fistula, vesicoureteral reflux,
urinary infections including epididymo-orchitis, and other urinary tract
anomalies on the conventional surgical management are illustrated.
PMID- 28413306
TI - Urogenital Management in Cloaca: An Alternative Approach.
AB - INTRODUCTION: In the management of cloaca, there is concern that dissection of
the urogenital sinus in early childhood with the aim of total anatomical
correction is hazardous. Avoiding such mobilization and providing mitrofanoff
channel, when needed, till peripubertal period reduces complications and is
technically easier. MATERIALS AND METHODS: Forty-three cases of cloaca were
managed in the period 2004-2016. Case records and radiology were reviewed
retrospectively. The follow-up evaluation was done by looking into voiding
history, bowel movements, and menstruation history. RESULTS: There were three
groups of children, namely, those with no reconstruction done elsewhere except a
diverting fecal stoma (Group I, n = 25), those who had undergone anorectal
correction elsewhere with no attempt at urogenital reconstruction (Group IIA, n =
13), and those with attempted bowel and genitourinary reconstruction elsewhere
(Group IIB, n = 5). The Group I children (one still awaiting reconstruction)
underwent early rectal reconstruction followed by expectant management of the
urogenital apparatus. The 18 referred cases had multiple problems, chiefly
urogenital, of congenital or iatrogenic origin. While urinary reconstruction
included bladder augmentation, ileal neobladder, bladder neck closure, and
ureteric reimplantation, the foundation of urinary management was intermittent
catheterization through mitrofanoff stoma and the avoidance of any dissection of
the cloacal common channel. Surgery on the genital tracts included drainage of
hydrocolpos, perineal surgery for low vaginae and abdominoperineal vaginoplasty
for high vaginae in the peripubertal period with or without bowel
supplementation. Spontaneous voiding was maintained in 17 of 25 (68%) Group I
girls (including one death later from intestinal complications), 7 of 13 (54%),
Group IIA girls, and 1 of 5 (20%) Group IIB girls. Painless menstruation was
noted in eight postpubertal girls, three through the cloacal channel (awaiting
reconstruction) and five through the reconstructed vagina. Most of the children
are on a bowel management program for fecal cleanliness with washouts through the
neoanus or Malone's stoma. CONCLUSION: We report a nonconventional approach to
cloaca based on avoiding dissection of or around the common channel for
urethrovaginal reconstruction, opting for mitrofanoff stoma for intermittent
catheterization, when needed, and late vaginal reconstruction. We believe this
approach has reduced the overall need for intermittent catheterization.
PMID- 28413307
TI - Laparoscopic-assisted Anorectoplasty: A Single-center Experience.
AB - AIM: To assess the modifications in the technique of laparoscopic-assisted
anorectal pull-through (LAARP) practiced at our institute and to analyze the
postoperative outcome and associated complications. MATERIALS AND METHODS: A
retrospective study was done to analyze the results for LAARP procedure done for
high anorectal malformations (ARMs) from January 2001 to May 2016. A total of 68
patients had undergone LAARP, with 62 male and 6 female children. Staged
procedure was done in 55 patients and one child with rectovestibular fistula of 5
months of age had a single-stage procedure. Technical modifications such as
traction over the fistula which helps in identification and dissection of the
puborectalis muscle, dividing the fistula without ligation, railroading with
Hegar's dilators over the suction cannula which creates adequate pull-through
channel, have helped save time and make the procedure simpler. The patients were
followed up with clinical evaluation and continence scoring. RESULTS: All the
patients withstood surgery well. One patient with rectovesical fistula required
conversion to gain adequate length of the distal rectum, for whom the colostomy
was closed and relocated at splenic flexure level. The complications were mucosal
prolapse (8 cases), anal stenosis (5), adhesive obstruction (2), distal rectal
necrosis (3), and urethral diverticulum (2). The progress has been satisfactory
and weight gain is adequate. 71.15% patients had good continence on follow-up.
CONCLUSION: LAARP procedure is safe for high ARMs with good continence and
correctable side effects. It has completely replaced posterior sagittal
anorectoplasty procedure for high anomalies in our practice.
PMID- 28413308
TI - Congenital Pouch Colon with Rectal Atresia Revisited.
AB - We are adding two cases of congenital pouch colon with rectal atresia (RA) to the
already published five cases. The presentation of RA is often delayed owing to
the presence of normal anus, however, clinical evaluation, plain abdominal
radiograph, and urine examination for meconuria, may help in detecting this rare
association early.
PMID- 28413309
TI - Type V Congenital Pouch Colon: An Extremely Rare Variant of Anorectal
Malformations.
AB - Type V is the rarest form of congenital pouch colon with only four cases reported
till date. We report this anomaly in a 6-month-old boy. He was managed
successfully with excision of distal pouch and coloplasty of proximal pouch along
with abdominoperineal posterior sagittal anorectoplasty. We recommend
preservation of proximal pouch in such cases.
PMID- 28413310
TI - Females with Externally Visible but Stenosed Fecal Orifice - Low or High
Anorectal Malformation.
AB - We report four female children with externally visible but stenosed fecal orifice
which proved to be a high anorectal malformation (Type IV pouch colon). They were
managed by an abdominoperineal approach with excellent results. We emphasize the
correct recognition of this pathology.
PMID- 28413311
TI - Persistent Cloaca: A Long-term Follow-up Study.
PMID- 28413313
TI - Additional Risk Minimisation Measures for Medicinal Products in the European
Union: A Review of the Implementation and Effectiveness of Measures in the United
Kingdom by One Marketing Authorisation Holder.
AB - INTRODUCTION: Additional risk minimisation measures (aRMMs) for medicinal
products are necessary to address specific important safety issues which may not
be practically achieved through routine risk management measures alone. The
implementation and determination of effectiveness for aRMMs can be a challenge as
it involves multiple stakeholders. It is therefore important to have concise
objectives to avoid undue burden on patients, healthcare professionals and the
healthcare system. AIM: The aim of this study was to examine how aRMMs are
implemented and how effectiveness is assessed in the European Union (EU) using
practical examples from Roche Products Limited in the United Kingdom (UK)
(referred to as the 'Company'). METHODS: Three centrally authorised products were
selected from the Company's portfolio, each of which had aRMMs to address
important safety concerns; specifically, teratogenicity, medication error and
infections. The implementation of EU aRMMs, effectiveness checks and specific UK
activities were analysed. Hard copy folders and electronic sites for Company
aRMMs were used to assess process indicators. Periodic benefit-risk evaluation
reports for specified time intervals and the Company safety database was used in
checking safety outcomes for the selected products. For each product, the
effectiveness of aRMMs was analysed based on specific process indicators and the
subsequent safety outcomes. Literature searches were performed on scientific
databases for the purposes of the broader study. RESULTS: The main process
indicators in measuring effectiveness of Company aRMMs were distribution metrics
for educational materials, assessment of awareness and clinical actions among
healthcare professionals (HCPs). Case reports of pregnancy, medication errors and
progressive multifocal leukoencephalopathy (PML) were the outcome indicators for
Erivedge(r)?, Kadcyla(r)? and MabThera(r) (the latter specifically in autoimmune
indications: rheumatoid arthritis, granulomatosis with polyangiitis and
microscopic polyangiitis) respectively. No pregnancy, one medication error and 10
confirmed PML cases were reported for Erivedge(r)?, Kadcyla(r)? and MabThera(r)
respectively. CONCLUSIONS: For the chosen products, a reasonable awareness of
aRMMs amongst HCPs is a positive indicator of success in the use of educational
materials. However, low response rates from surveys indicate that voluntary
feedback may not always achieve the desired level of response in measuring
effectiveness. There is a challenge in determining overall effectiveness of aRMMs
due to a lack of defined success thresholds. Further regulatory guidance to
outline the elements and desired outcomes of aRMMs will be useful for consistency
in achieving successful outcomes.
PMID- 28413312
TI - Low-Income, African American, Adolescent Mothers' Depressive Symptoms, Perceived
Stress, and Social Support.
AB - The purpose of this descriptive repeated-measures study was to describe
depressive symptom patterns and report changes over time in levels of perceived
stress and social support depending on patterns of depressive symptoms in single,
low-income, African American, adolescent mothers during the initial, 6-month
postpartum period. Thirty-five adolescent subjects between the ages of 16 and 22
years old were recruited at health care clinics in two Midwestern cities. Data
collections by advanced practice nurses were completed at 1 week, 6 weeks, 3
months, and 6 months postpartum at mothers' homes. Established instruments were
used to measure depressive symptoms, perceived stress and social support. Results
indicated 63% of adolescent mothers' experienced depressive symptoms sometime
during this transition period and 11.4% of these subjects had depressive symptoms
at all 4 time points. Depressive symptoms were associated with perceived stress
at each time point. Emotional support was inversely associated with depressive
symptoms at 2 of the 4 time points. Depressive symptoms and problematic support
were significantly related at 3 months and 6 months. Although single, low-income,
African American, adolescent mothers are considered a high risk group, some are
at even greater risk. This extremely high risk group have depressive symptoms
throughout the first 6 months postpartum with the highest level of perceived
stress and the most variability in social support relative to groups that were
never depressed or were in and out of depression. More studies are needed to
understand how to best help these high risk adolescents successfully transition
to motherhood.
PMID- 28413314
TI - Implications of red Panax ginseng in oxidative stress associated chronic
diseases.
AB - The steaming process of Panax ginseng has been reported to increase its major
known bioactive components, ginsenosides, and, therefore, its biological
properties as compared to regular Panax ginseng. Biological functions of red
Panax ginseng attenuating pro-oxidant environments associated with chronic
diseases are of particular interest, since oxidative stress can be a key
contributor to the pathogenesis of chronic diseases. Additionally, proper
utilization of various biomarkers for evaluating antioxidant activities in
natural products, such as ginseng, can also be important to providing validity to
their activities. Thus, studies on the effects of red ginseng against various
diseases as determined in cell lines, animal models, and humans were reviewed,
along with applied biomarkers for verifying such effects. Limitations and future
considerations of studying red ginseng were been discussed. Although further
clinical studies are warranted, red ginseng appears to be beneficial for
attenuating disease-associated symptoms via its antioxidant activities, as well
as for preventing oxidative stress-associated chronic diseases.
PMID- 28413315
TI - The involvement of ginseng berry extract in blood flow via regulation of blood
coagulation in rats fed a high-fat diet.
AB - BACKGROUND: The present study investigated the effect of ginseng berry hot water
extract (GBx) on blood flow via the regulation of lipid metabolites and blood
coagulation in rats fed a high-fat diet (HFD). METHODS: Sixty rats were divided
into five groups in descending order of body weight. Except for the control
group, the other four groups were fed a HFD containing 45% kcal from fat for 11
wk without GBx. GBx groups were then additionally treated by gastric gavage with
GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or
150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the
effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation
assay, and histological analysis were performed. RESULTS: In the experiments to
measure the serum levels of leptin and apolipoprotein B/A, GBx treatment
attenuated the HFD-induced increases in these metabolites (p < 0.05). Adiponectin
and apolipoprotein E levels in GBx-treated groups were significantly higher than
the HFD group. Prothrombin time and activated partial thromboplastin time were
increased in all GBx-treated groups. In the GBx-treated groups, the serum levels
of thromboxane A2 and serotonin were decreased and concentrations of serum
fibrinogen degradation products were increased (p < 0.05). Moreover,
histomorphometric dyslipidemia-related atherosclerotic changes were significantly
improved by treatment with GBx. CONCLUSION: These results suggest the possibility
that GBx can ameliorate blood flow by decreasing intima-media thickness via the
regulation of blood coagulation factors related to lipid metabolites in rats fed
a HFD.
PMID- 28413316
TI - Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting
TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2.
AB - BACKGROUND: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type
saponins isolated from Panax ginseng, a well-known medicinal herb with many
beneficial properties including anticancer, anti-inflammatory, antiobesity, and
antidiabetic effects. In this study, we investigated the effects of G-Rc on
inflammatory responses in vitro and examined the mechanisms of these effects.
METHODS: The in vitro inflammation system used lipopolysaccharide-treated
macrophages, tumor necrosis factor-alpha/interferon-gamma-treated synovial cells,
and HEK293 cells transfected with various inducers of inflammation. RESULTS: G-Rc
significantly inhibited the expression of macrophage-derived cytokines, such as
tumor necrosis factor-alpha and interleukin-1beta. G-Rc also markedly suppressed
the activation of TANK-binding kinase 1/IkappaB kinase epsilon/interferon
regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages,
human synovial cells, and HEK293 cells. CONCLUSION: G-Rc exerts its anti
inflammatory actions by suppressing TANK-binding kinase 1/IkappaB kinase
epsilon/interferon regulatory factor-3 and p38/ATF-2 signaling.
PMID- 28413317
TI - Korean Red Ginseng improves atopic dermatitis-like skin lesions by suppressing
expression of proinflammatory cytokines and chemokines in vivo and in vitro.
AB - BACKGROUND: The prevalence of allergic inflammatory diseases such as atopic
dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and
complete recovery is difficult. Korean Red Ginseng, which is the heat-processed
root of Panax ginseng Meyer, is widely and frequently used as a traditional
medicine in East Asia. In this study, we investigated whether Korean Red Ginseng
water extract (RGE) regulates the expression of proinflammatory cytokines and
chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa
B (NF-kappaB) pathway in allergic inflammation. METHODS: Compound 48/80-induced
anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin
lesion mice models were used to investigate the antiallergic effects of RGE.
Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to
clarify the effects of RGE on the expression of proinflammatory cytokines and
chemokines. RESULTS: Anaphylactic shock and DNFB-induced AD-like skin lesions
were attenuated by RGE administration through reduction of serum immunoglobulin E
(IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the
production of proinflammatory cytokines including IL-1beta, IL-6, and IL-8, and
expression of chemokines such as IL-8, thymus and activation-regulated chemokine
(TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE
decreased the release of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6,
and IL-8 as well as expressions of chemokines including macrophage inflammatory
protein (MIP)-1alpha, MIP-1beta, regulated on activation, normal T cell expressed
and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC
1 cells. Furthermore, our data demonstrated that these inhibitory effects
occurred through blockage of the MAPK and NF-kappaB pathway. CONCLUSION: RGE may
be a useful therapeutic agent for the treatment of allergic inflammatory diseases
such as AD-like dermatitis.
PMID- 28413318
TI - Genetic defects in the nef gene are associated with Korean Red Ginseng intake:
monitoring of nef sequence polymorphisms over 20 years.
AB - BACKGROUND: The presence of gross deletions in the human immunodeficiency virus
nef gene (gDeltanef) is associated with long-term nonprogression of infected
patients. Here, we investigated how quickly genetic defects in the nef gene are
associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors.
METHODS: This study was divided into three phases over a 20-yr period; baseline,
KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef
gene amplicons were obtained using reverse transcription polymerase chain
reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and
nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and
these were then sequenced. The proportion of gDeltanef, premature stop codons,
and not in-frame insertion or deletion of a nucleotide was compared between three
phases, control, and ART patients. RESULTS: The proportion of defective nef genes
was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%),
control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p <
0.01). Small in-frame deletions or insertions were significantly more frequent
among patients treated with KRG alone compared with controls (p < 0.01).
Significantly fewer instances of genetic defects were detected in samples taken
during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected
were gDeltanef and small in-frame deletions after 7 mo and 67 mo of KRG intake,
respectively. CONCLUSION: KRG treatment might induce genetic defects in the nef
gene. This report provides new insight into the importance of genetic defects in
the pathogenesis of AIDS.
PMID- 28413319
TI - Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning
behavior in rats and elicit anti-inflammatory effects in vitro.
AB - BACKGROUND: Chong-Myung-Tang (CMT) extract is widely used in Korea as a
traditional herbal tonic for increasing memory capacity in high-school students
and also for numerous body ailments since centuries. The use of CMT to improve
the learning capacity has been attributed to various plant constituents,
especially black ginseng, in it. Therefore, in this study, we have first
investigated whether black ginseng-enriched CMT extracts affected spatial
learning using the Morris water maze (MWM) test. Their molecular mechanism of
action underlying improvement of learning and memory was examined in vitro.
METHODS: We used two types of black ginseng-enriched CMT extracts, designated as
CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning
behavior and their anti-inflammatory effects in BV2 microglial cells. RESULTS:
Our results show that both black ginseng-enriched CMT extracts improved the
learning behavior in scopolamine-induced impairment in the water maze test.
Moreover, these extracts also inhibited nitric oxide production in BV2 cells,
with significant suppression of expression of proinflammatory cytokines,
especially inducible nitric oxide synthase, cyclooxygenase-2, and interleukin
1beta. The protein expression of mitogen-activated protein kinase and nuclear
factor-kappaB pathway factors was also diminished by black ginseng-enriched CMT
extracts, indicating that it not only improves the memory impairment, but also
acts a potent anti-inflammatory agent for neuroinflammatory diseases. CONCLUSION:
Our research for the first time provides the scientific evidence that consumption
of black ginseng-enriched CMT extract as a brain tonic improves memory
impairment. Thus, our study results can be taken as a reference for future
neurobehavioral studies.
PMID- 28413320
TI - Panax ginseng Meyer prevents radiation-induced liver injury via modulation of
oxidative stress and apoptosis.
AB - BACKGROUND: Radiotherapy is one of the most important modalities in cancer
treatment; however, normal tissue damage is a serious concern. Drug development
for the protection or reduction of normal tissue damage is therefore a clinical
issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and
its corresponding mechanisms. METHODS: C56BL/6 mice were orally pretreated with
P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or
intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then
exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of
irradiation, the biological properties of hematoxicity, fat accumulation,
histopathology, oxidative stress, antioxidant activity, pro-inflammatory
cytokines, and apoptosis signals were examined in the hepatic tissue. RESULTS:
The irradiation markedly induced myelosuppression as determined by hematological
analysis of the peripheral blood. Steatohepatitis was induced by X-ray
irradiations, whereas pretreatment with PGE significantly attenuated it.
Oxidative stress was drastically increased, whereas antioxidant components were
depleted by irradiation. Irradiation also notably increased serum liver enzymes
and hepatic protein levels of pro-inflammatory cytokines. Those alterations were
markedly normalized by pretreatment with PGE. The degree of irradiation-induced
hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was
evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'
triphosphate nick-end labeling assay, western blotting, and gene expressions
analysis, particularly of apoptotic molecules. CONCLUSION: We suggest that PGE
could be applicable for use against radiation-induced liver injury, and its
corresponding mechanisms involve the modulation of oxidative stress, inflammatory
reactions, and apoptosis.
PMID- 28413322
TI - Improved antimicrobial effect of ginseng extract by heat transformation.
AB - BACKGROUND: The incidence of halitosis has a prevalence of 22-50% throughout the
world and is generally caused by anaerobic oral microorganisms, such as
Fusobacterium nucleatum, Clostridium perfringens, and Porphyromonas gingivalis.
Previous investigations on the structure-activity relationships of ginsenosides
have led to contrasting results. Particularly, the antibacterial activity of less
polar ginsenosides against halitosis-related bacteria has not been reported.
METHODS: Crude saponins extracted from the Panax quinquefolius leaf-stem (AGS)
were treated at 130 degrees C for 3 h to obtain heat-transformed saponins (HTS).
Five ginsenoside-enriched fractions (HTS-1, HTS-2, HTS-3, HTS-4, and HTS-5) and
less polar ginsenosides were separated by HP-20 resin absorption and HPLC, and
the antimicrobial activity and mechanism were investigated. RESULTS: HPLC with
diode-array detection analysis revealed that heat treatment induced an extensive
conversion of polar ginsenosides (-Rg1/Re, -Rc, -Rb2, and -Rd) to less polar
compounds (-Rg2, -Rg3, -Rg6, -F4, -Rg5, and -Rk1). The antimicrobial assays
showed that HTS, HTS-3, and HTS-4 were effective at inhibiting the growth of F.
nucleatum, C. perfringens, and P. gingivalis. Ginsenosides-Rg5 showed the best
antimicrobial activity against the three bacteria, with the lowest values of
minimum inhibitory concentration and minimum bactericidal concentration. One
major reason for this result is that less polar ginsenosides can more easily
damage membrane integrity. CONCLUSION: The results indicated that the less polar
ginsenoside-enriched fraction from heat transformation can be used as an
antibacterial agent to control halitosis.
PMID- 28413321
TI - The beneficial effect of ginsenosides extracted by pulsed electric field against
hydrogen peroxide-induced oxidative stress in HEK-293 cells.
AB - BACKGROUND: Ginsenosides are the main pharmacological components of Panax ginseng
root, which are thought to be primarily responsible for the suppressing effect on
oxidative stress. METHODS: 2,2-diphenyl-1-picrylhydrazyl radical scavenging
activity and oxygen radical absorption capacity were applied to evaluate the
antioxidant activities of the ginsenosides. Human embryonic kidney 293 (HEK-293)
cells were incubated with ginsenosides extracted by pulsed electric field (PEF)
and solvent cold soak extraction (SCSE) for 24 h and then the injury was induced
by 40MUM H2O2. The cell viability and surface morphology of HEK-293 cells were
studied using MTS assay and scanning electron microscopy, respectively. Dichloro
dihydro-fluorescein diacetate fluorescent probe assay was used to measure the
level of intracellular reactive oxygen species. The intracellular antioxidant
activities of ginsenosides were evaluated by cellular antioxidant activity assay
in HepG2 cells. RESULTS: The PEF extracts displayed the higher 2,2-diphenyl-1
picrylhydrazyl radical scavenging activity and stronger oxygen radical absorption
capacity (with an oxygen radical absorption capacity value of 14.48 +/- 4.04MUM
TE per MUg/mL). The HEK-293 cell model also suggested that the protective effect
of PEF extracts was dose-dependently greater than SCSE extracts. Dichloro-dihydro
fluorescein diacetate assay further proved that PEF extracts are more active (8%
higher than SCSE extracts) in reducing intracellular reactive oxygen species
accumulation. In addition, scanning electron microscopy images showed that the
HEK-293 cells, which were treated with PEF extracts, maintained more intact
surface morphology. Cellular antioxidant activity values indicated that
ginsenosides extracted by PEF had stronger cellular antioxidant activity than
SCSE ginsenosides extracts. CONCLUSION: The present study demonstrated the
antioxidative effect of ginsenosides extracted by PEF in vitro. Furthermore,
rather than SCSE, PEF may be more useful as an alternative extraction technique
for the extraction of ginsenosides with enhanced antioxidant activity.
PMID- 28413323
TI - Preventive effect of fermented black ginseng against cisplatin-induced
nephrotoxicity in rats.
AB - BACKGROUND: Fermented black ginseng (FBG) is processed ginseng by the repeated
heat treatment and fermentation of raw ginseng. The protective effect and
mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate
its therapeutic potential. METHODS: The free radical scavenging activity of FBG
was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the
protective effect against cisplatin-induced renal damage was tested in rats. FBG
was orally administered every day at a dose of 150 mg/kg body weight for 10 d,
and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body
weight) with 0.9% saline on the 4th d. RESULTS: The DPPH radical-scavenging
activity of FBG (IC50 = 384 MUg/mL) was stronger than that of raw ginseng. The
improved DPPH radical-scavenging activity was mediated by the generation phenolic
compounds. The decreased cell viability by cisplatin was recovered significantly
after treatment with FBG in a dose-dependent manner. Then, the protective effect
of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The
decreased creatinine clearance levels, which are a reliable marker for renal
dysfunction in cisplatin-treated rats, were reduced to the normal level after the
administration of FBG. Moreover, FBG showed protective effects against cisplatin
induced oxidative renal damage in rats through the inhibition of NF-kappaB/p65,
COX-2, and caspase-3 activation. CONCLUSION: These results collectively show that
the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating
oxidative stress, inflammation, and apoptosis.
PMID- 28413324
TI - Ginseng authenticity testing by measuring carbon, nitrogen, and sulfur stable
isotope compositions that differ based on cultivation land and organic fertilizer
type.
AB - BACKGROUND: The natural ratios of carbon (C), nitrogen (N), and sulfur (S) stable
isotopes can be varied in some specific living organisms owing to various
isotopic fractionation processes in nature. Therefore, the analysis of C, N, and
S stable isotope ratios in ginseng can provide a feasible method for determining
ginseng authenticity depending on the cultivation land and type of fertilizer.
METHODS: C, N, and S stable isotope composition in 6-yr-old ginseng roots
(Jagyeongjong variety) was measured by isotope ratio mass spectrometry. RESULTS:
The type of cultivation land and organic fertilizers affected the C, N, and S
stable isotope ratio in ginseng (p < 0.05). The delta15NAIR and delta34SVCDT
values in ginseng roots more significantly discriminated the cultivation land and
type of organic fertilizers in ginseng cultivation than the delta13CVPDB value.
The combination of delta13CVPDB, delta15NAIR, or delta34SVCDT in ginseng, except
the combination delta13CVPDB-34SVCDT, showed a better discrimination depending on
soil type or fertilizer type. CONCLUSION: This case study provides preliminary
results about the variation of C, N, and S isotope composition in ginseng
according to the cultivation soil type and organic fertilizer type. Hence, our
findings are potentially applicable to evaluate ginseng authenticity depending on
cultivation conditions.
PMID- 28413325
TI - The psychopharmacological activities of Vietnamese ginseng in mice:
characterization of its psychomotor, sedative-hypnotic, antistress, anxiolytic,
and cognitive effects.
AB - BACKGROUND: Panax vietnamensis Ha et Grushv. or Vietnamese ginseng (VG) is a
recently discovered ginseng species. Studies on its chemical constituents have
shown that VG is remarkably rich in ginseng saponins, particularly ocotillol
saponins. However, the psychopharmacological effects of VG have not been
characterized. Thus, in the present study we screened the psychopharmacological
activities of VG in mice. METHODS: VG extract (VGE) was orally administered to
mice at various dosages to evaluate its psychomotor (open-field and rota-rod
tests), sedative-hypnotic (pentobarbital-induced sleeping test), antistress (cold
swimming test), anxiolytic (elevated plus-maze test), and cognitive (Y-maze and
passive-avoidance tests) effects. RESULTS: VGE treatment increased the
spontaneous locomotor activity, enhanced the endurance to stress, reduced the
anxiety-like behavior, and ameliorated the scopolamine-induced memory impairments
in mice. In addition, VGE treatment did not alter the motor balance and
coordination of mice and did not potentiate pentobarbital-induced sleep,
indicating that VGE has no sedative-hypnotic effects. The effects of VGE were
comparable to those of the Korean Red Ginseng extract. CONCLUSION: VG, like other
ginseng products, has significant and potentially useful psychopharmacological
effects. This includes, but is not limited to, psychomotor stimulation,
anxiolytic, antistress, and memory enhancing effects.
PMID- 28413326
TI - Effect of B-complex vitamins on the antifatigue activity and bioavailability of
ginsenoside Re after oral administration.
AB - BACKGROUND: Both ginsenoside Re and B-complex vitamins are widely used as
nutritional supplements. They are often taken together so as to fully utilize
their antifatigue and refreshing effects, respectively. Whether actually a drug
nutrient interaction exists between ginsenoside Re and B-complex vitamins is
still unknown. The objective of this study was to simultaneously investigate the
effect of B-complex vitamins on the antifatigue activity and bioavailability of
ginsenoside Re after their oral administration. The study results will provide
valuable theoretical guidance for the combined utilization of ginseng and B
complex vitamins. METHODS: Ginsenoside Re with or without B-complex vitamins was
orally administered to mice to evaluate its antifatigue effects and to rats to
evaluate its bioavailability. The antifatigue activity was evaluated by the
weight-loaded swimming test and biochemical parameters, including hepatic
glycogen, plasma urea nitrogen, and blood lactic acid. The concentration of
ginsenoside Re in plasma was determined by liquid chromatography-tandem mass
spectrometry. RESULTS: No antifatigue effect of ginsenoside Re was noted when
ginsenoside Re in combination with B-complex vitamins was orally administered to
mice. B-complex vitamins caused to a reduction in the bioavailability of
ginsenoside Re with the area under the concentration-time curve from zero to
infinity markedly decreasing from 11,830.85 +/- 2,366.47 h.ng/mL to 890.55 +/-
372.94 h.ng/mL. CONCLUSION: The results suggested that there were pharmacokinetic
and pharmacodynamic drug-nutrient interactions between ginsenoside Re and B
complex vitamins. B-complex vitamins can significantly weaken the antifatigue
effect and decrease the bioavailability of ginsenoside Re when simultaneously
administered orally.
PMID- 28413328
TI - Effect of Korean Red Ginseng intake on the survival duration of human
immunodeficiency virus type 1 patients.
AB - BACKGROUND: Long-term ginseng intake can increase longevity in healthy
individuals. Here, we examined if long-term treatment with Panax ginseng Meyer
(Korean Red Ginseng, KRG) can also enhance survival duration (SD) in patients
with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We
retrospectively analyzed 252 HIV-1 patients diagnosed from 1986 to 2013 prior to
the initiation of antiretroviral therapy. Overall, 162 patients were treated with
KRG (3,947 +/- 4,943 g) for 86 +/- 63 mo. The effects of KRG on SD were analyzed
according to the KRG intake level and the length of the follow-up period.
RESULTS: There were significant correlations between the total amount of KRG and
SD in the KRG intake group (r = 0.64, p < 0.0001) as well as between total amount
of KRG and mean annual decrease in CD4+ T-cell count in all 252 patients (r =
0.17, p < 0.01). The annual decrease in CD4+ T-cell count (change in cells/MUL)
was significantly slower in KRG-treated patients than in patients receiving no
KRG (48 +/- 40 vs. 106 +/- 162; p < 0.001). The SD (in months) was also
significantly longer in the KRG group than in the no-KRG group (101 +/- 64 vs. 59
+/- 40, p < 0.01). CONCLUSION: KRG prolongs survival in HIV-1 patients, possibly
by slowing the decrease in CD4+ T-cell count.
PMID- 28413327
TI - Effects of ginseng on two main sex steroid hormone receptors: estrogen and
androgen receptors.
AB - Ginseng has been used in China for at least two millennia and is now popular in
over 35 countries. It is one of the world's popular herbs for complementary and
alternative medicine and has been shown to have helpful effects on cognition and
blood circulation, as well as anti-aging, anti-cancer, and anti-diabetic effects,
among many others. The pharmacological activities of ginseng are dependent mainly
on ginsenosides. Ginsenosides have a cholesterol-like four trans-ring steroid
skeleton with a variety of sugar moieties. Nuclear receptors are one of the most
important molecular targets of ginseng, and reports have shown that members of
the nuclear receptor superfamily are regulated by a variety of ginsenosides.
Here, we review the published literature on the effects of ginseng and its
constituents on two main sex steroid hormone receptors: estrogen and androgen
receptors. Furthermore, we discuss applications for sex steroid hormone receptor
modulation and their therapeutic efficacy.
PMID- 28413329
TI - Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in
LLC-PK1 kidney cells.
AB - BACKGROUND: Ginsenosides are active components of Panax ginseng that exert
various health benefits including kidney protection effect. The medicinal
activity of ginsenosides can be enhanced by modulating their stereospecificity by
heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the
double bond at C-20(21) or C-20(22). METHODS: The present study investigated the
kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a
platinum based anticancer drug, induced apoptotic damage in renal proximal LLC
PK1 cells. RESULTS: As a result, ginsenoside Rh3 shows a stronger protective
effect than that shown by Rk2. Cisplatin-induced elevated protein levels of
phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated
kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with
ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells
induced by cisplatin treatment also significantly reduced after cotreatment with
ginsenoside Rh3. CONCLUSION: These results demonstrate that inhibition of the JNK
and ERK mitogen-activated protein kinase signaling cascade plays a critical role
in mediating the renoprotective effect of ginsenoside Rh3.
PMID- 28413331
TI - A laboratory study of nonlinear changes in the directionality of extreme seas.
AB - This paper concerns the description of surface water waves, specifically
nonlinear changes in the directionality. Supporting calculations are provided to
establish the best method of directional wave generation, the preferred method of
directional analysis and the inputs on which such a method should be based. These
calculations show that a random directional method, in which the phasing,
amplitude and direction of propagation of individual wave components are chosen
randomly, has benefits in achieving the required ergodicity. In terms of analysis
procedures, the extended maximum entropy principle, with inputs based upon vector
quantities, produces the best description of directionality. With laboratory data
describing the water surface elevation and the two horizontal velocity components
at a single point, several steep sea states are considered. The results confirm
that, as the steepness of a sea state increases, the overall directionality of
the sea state reduces. More importantly, it is also shown that the largest waves
become less spread or more unidirectional than the sea state as a whole. This
provides an important link to earlier descriptions of deterministic wave groups
produced by frequency focusing, helps to explain recent field observations and
has important practical implications for the design of marine structures and
vessels.
PMID- 28413332
TI - Fluid dynamics of acoustic and hydrodynamic cavitation in hydraulic power
systems.
AB - Cavitation is the transition from a liquid to a vapour phase, due to a drop in
pressure to the level of the vapour tension of the fluid. Two kinds of cavitation
have been reviewed here: acoustic cavitation and hydrodynamic cavitation. As
acoustic cavitation in engineering systems is related to the propagation of waves
through a region subjected to liquid vaporization, the available expressions of
the sound speed are discussed. One of the main effects of hydrodynamic cavitation
in the nozzles and orifices of hydraulic power systems is a reduction in flow
permeability. Different discharge coefficient formulae are analysed in this
paper: the Reynolds number and the cavitation number result to be the key fluid
dynamical parameters for liquid and cavitating flows, respectively. The latest
advances in the characterization of different cavitation regimes in a nozzle, as
the cavitation number reduces, are presented. The physical cause of choked flows
is explained, and an analogy between cavitation and supersonic aerodynamic flows
is proposed. The main approaches to cavitation modelling in hydraulic power
systems are also reviewed: these are divided into homogeneous-mixture and two
phase models. The homogeneous-mixture models are further subdivided into
barotropic and baroclinic models. The advantages and disadvantages of an
implementation of the complete Rayleigh-Plesset equation are examined.
PMID- 28413333
TI - Equilibrium shapes of a heterogeneous bubble in an electric field: a variational
formulation and numerical verifications.
AB - The equilibrium shape of a bubble/droplet in an electric field is important for
electrowetting over dielectrics (EWOD), electrohydrodynamic (EHD) enhancement for
heat transfer and electro-deformation of a single biological cell among others.
In this work, we develop a general variational formulation in account of electro
mechanical couplings. In the context of EHD, we identify the free energy
functional and the associated energy minimization problem that determines the
equilibrium shape of a bubble in an electric field. Based on this variational
formulation, we implement a fixed mesh level-set gradient method for computing
the equilibrium shapes. This numerical scheme is efficient and validated by
comparing with analytical solutions at the absence of electric field and
experimental results at the presence of electric field. We also present
simulation results for zero gravity which will be useful for space applications.
The variational formulation and numerical scheme are anticipated to have broad
applications in areas of EWOD, EHD and electro-deformation in biomechanics.
PMID- 28413330
TI - Toxoplasmosis seroprevalence in Iranian women and risk factors of the disease: a
systematic review and meta-analysis.
AB - BACKGROUND: Toxoplasmosis is caused by an intracellular obligatory parasite,
Toxoplasma gondii, and it has global distribution. The purposes of this
systematic review and meta-analysis were to evaluate the seroprevalence of
toxoplasmosis in Iranian pregnant women, and girls and women of childbearing age,
and identify potentially preventable risk factors. METHODS: Between November 2014
and February 2017, nine electronic databases that reported data on the T. gondii
seroprevalence in Iranian women were searched. Our search resulted in 83 reports
published from 1994 to 2017. RESULTS: The results showed that the pooled
estimation for the prevalence of T. gondii using a random-effect model was 43%
(95% confidence interval (CI) = 38-48%) in pregnant women and 33% (95% CI = 23
43%) in girls and the childbearing age groups. There was a significant
association between the T. gondii seroprevalence with age and the gestational age
of conception in pregnant women and those who had contact with cats in both
groups. CONCLUSIONS: This is the first comprehensive systematic review of T.
gondii infection seroprevalence in Iranian women, which showed a high prevalence
of Toxoplasma infection. Around 57% of pregnant women and 67% of girls and the
childbearing age groups were seronegative and thus were susceptible to infection
and should be monitored.
PMID- 28413334
TI - Landslides and tsunamis predicted by incompressible smoothed particle
hydrodynamics (SPH) with application to the 1958 Lituya Bay event and idealized
experiment.
AB - Tsunamis caused by landslides may result in significant destruction of the
surroundings with both societal and industrial impact. The 1958 Lituya Bay
landslide and tsunami is a recent and well-documented terrestrial landslide
generating a tsunami with a run-up of 524 m. Although recent computational
techniques have shown good performance in the estimation of the run-up height,
they fail to capture all the physical processes, in particular, the landslide
entry profile and interaction with the water. Smoothed particle hydrodynamics
(SPH) is a versatile numerical technique for describing free-surface and multi
phase flows, particularly those that exhibit highly nonlinear deformation in
landslide-generated tsunamis. In the current work, the novel multi-phase
incompressible SPH method with shifting is applied to the Lituya Bay tsunami and
landslide and is the first methodology able to reproduce realistically both the
run-up and landslide-entry as documented in a benchmark experiment. The method is
the first paper to develop a realistic implementation of the physics that in
addition to the non-Newtonian rheology of the landslide includes turbulence in
the water phase and soil saturation. Sensitivity to the experimental initial
conditions is also considered. This work demonstrates the ability of the proposed
method in modelling challenging environmental multi-phase, non-Newtonian and
turbulent flows.
PMID- 28413335
TI - Superregular breathers, characteristics of nonlinear stage of modulation
instability induced by higher-order effects.
AB - We study the higher-order generalized nonlinear Schrodinger (NLS) equation
describing the propagation of ultrashort optical pulse in optical fibres. By
using Darboux transformation, we derive the superregular breather solution that
develops from a small localized perturbation. This type of solution can be used
to characterize the nonlinear stage of the modulation instability (MI) of the
condensate. In particular, we show some novel characteristics of the nonlinear
stage of MI arising from higher-order effects: (i) coexistence of a quasi
Akhmediev breather and a multipeak soliton; (ii) two multipeak solitons
propagation in opposite directions; (iii) a beating pattern followed by two
multipeak solitons in the same direction. It is found that these patterns
generated from a small localized perturbation do not have the analogues in the
standard NLS equation. Our results enrich Zakharov's theory of superregular
breathers and could provide helpful insight on the nonlinear stage of MI in
presence of the higher-order effects.
PMID- 28413336
TI - A restatement of the natural science evidence concerning catchment-based
'natural' flood management in the UK.
AB - Flooding is a very costly natural hazard in the UK and is expected to increase
further under future climate change scenarios. Flood defences are commonly
deployed to protect communities and property from flooding, but in recent years
flood management policy has looked towards solutions that seek to mitigate flood
risk at flood-prone sites through targeted interventions throughout the
catchment, sometimes using techniques which involve working with natural
processes. This paper describes a project to provide a succinct summary of the
natural science evidence base concerning the effectiveness of catchment-based
'natural' flood management in the UK. The evidence summary is designed to be read
by an informed but not technically specialist audience. Each evidence statement
is placed into one of four categories describing the nature of the underlying
information. The evidence summary forms the appendix to this paper and an
annotated bibliography is provided in the electronic supplementary material.
PMID- 28413337
TI - Device-independent tests of quantum channels.
AB - We develop a device-independent framework for testing quantum channels. That is,
we falsify a hypothesis about a quantum channel based only on an observed set of
input-output correlations. Formally, the problem consists of characterizing the
set of input-output correlations compatible with any arbitrary given quantum
channel. For binary (i.e. two input symbols, two output symbols) correlations, we
show that extremal correlations are always achieved by orthogonal encodings and
measurements, irrespective of whether or not the channel preserves commutativity.
We further provide a full, closed-form characterization of the sets of binary
correlations in the case of: (i) any dihedrally covariant qubit channel (such as
any Pauli and amplitude-damping channels) and (ii) any universally-covariant
commutativity-preserving channel in an arbitrary dimension (such as any erasure,
depolarizing, universal cloning and universal transposition channels).
PMID- 28413338
TI - The cross-over to magnetostrophic convection in planetary dynamo systems.
AB - Global scale magnetostrophic balance, in which Lorentz and Coriolis forces
comprise the leading-order force balance, has long been thought to describe the
natural state of planetary dynamo systems. This argument arises from
consideration of the linear theory of rotating magnetoconvection. Here we test
this long-held tenet by directly comparing linear predictions against dynamo
modelling results. This comparison shows that dynamo modelling results are not
typically in the global magnetostrophic state predicted by linear theory. Then,
in order to estimate at what scale (if any) magnetostrophic balance will arise in
nonlinear dynamo systems, we carry out a simple scaling analysis of the Elsasser
number Lambda, yielding an improved estimate of the ratio of Lorentz and Coriolis
forces. From this, we deduce that there is a magnetostrophic cross-over length
scale, [Formula: see text], where Lambdao is the linear (or traditional) Elsasser
number, Rmo is the system scale magnetic Reynolds number and D is the length
scale of the system. On scales well above [Formula: see text], magnetostrophic
convection dynamics should not be possible. Only on scales smaller than [Formula:
see text] should it be possible for the convective behaviours to follow the
predictions for the magnetostrophic branch of convection. Because [Formula: see
text] is significantly smaller than the system scale in most dynamo models, their
large-scale flows should be quasi-geostrophic, as is confirmed in many dynamo
simulations. Estimating Lambdao ?1 and Rmo ?103 in Earth's core, the cross-over
scale is approximately 1/1000 that of the system scale, suggesting that
magnetostrophic convection dynamics exists in the core only on small scales below
those that can be characterized by geomagnetic observations.
PMID- 28413339
TI - Efficient generation of receiver operating characteristics for the evaluation of
damage detection in practical structural health monitoring applications.
AB - Permanently installed guided wave monitoring systems are attractive for
monitoring large structures. By frequently interrogating the test structure over
a long period of time, such systems have the potential to detect defects much
earlier than with conventional one-off inspection, and reduce the time and labour
cost involved. However, for the systems to be accepted under real operational
conditions, their damage detection performance needs to be evaluated in these
practical settings. The receiver operating characteristic (ROC) is an established
performance metric for one-off inspections, but the generation of the ROC
requires many test structures with realistic damage growth at different locations
and different environmental conditions, and this is often impractical. In this
paper, we propose an evaluation framework using experimental data collected over
multiple environmental cycles on an undamaged structure with synthetic damage
signatures added by superposition. Recent advances in computation power enable
examples covering a wide range of practical scenarios to be generated, and for
multiple cases of each scenario to be tested so that the statistics of the
performance can be evaluated. The proposed methodology has been demonstrated
using data collected from a laboratory pipe specimen over many temperature
cycles, superposed with damage signatures predicted for a flat-bottom hole
growing at different rates at various locations. Three damage detection schemes,
conventional baseline subtraction, singular value decomposition (SVD) and
independent component analysis (ICA), have been evaluated. It has been shown that
in all cases, the component methods perform significantly better than the
residual method, with ICA generally the better of the two. The results have been
validated using experimental data monitoring a pipe in which a flat-bottom hole
was drilled and enlarged over successive temperature cycles. The methodology can
be used to evaluate the performance of an installed monitoring system and to show
whether it is capable of detecting particular damage growth at any given
location. It will enable monitoring results to be evaluated rigorously and will
be valuable in the development of safety cases.
PMID- 28413340
TI - History dependence and the continuum approximation breakdown: the impact of
domain growth on Turing's instability.
AB - A diffusively driven instability has been hypothesized as a mechanism to drive
spatial self-organization in biological systems since the seminal work of Turing.
Such systems are often considered on a growing domain, but traditional
theoretical studies have only treated the domain size as a bifurcation parameter,
neglecting the system non-autonomy. More recently, the conditions for a
diffusively driven instability on a growing domain have been determined under
stringent conditions, including slow growth, a restriction on the temporal
interval over which the prospect of an instability can be considered and a
neglect of the impact that time evolution has on the stability properties of the
homogeneous reference state from which heterogeneity emerges. Here, we firstly
relax this latter assumption and observe that the conditions for the Turing
instability are much more complex and depend on the history of the system in
general. We proceed to relax all the above constraints, making analytical
progress by focusing on specific examples. With faster growth, instabilities can
grow transiently and decay, making the prediction of a prospective Turing
instability much more difficult. In addition, arbitrarily high spatial
frequencies can destabilize, in which case the continuum approximation is
predicted to break down.
PMID- 28413341
TI - SPARSE-A subgrid particle averaged Reynolds stress equivalent model: testing with
a priori closure.
AB - A Lagrangian particle cloud model is proposed that accounts for the effects of
Reynolds-averaged particle and turbulent stresses and the averaged carrier-phase
velocity of the subparticle cloud scale on the averaged motion and velocity of
the cloud. The SPARSE (subgrid particle averaged Reynolds stress equivalent)
model is based on a combination of a truncated Taylor expansion of a drag
correction function and Reynolds averaging. It reduces the required number of
computational parcels to trace a cloud of particles in Eulerian-Lagrangian
methods for the simulation of particle-laden flow. Closure is performed in an a
priori manner using a reference simulation where all particles in the cloud are
traced individually with a point-particle model. Comparison of a first-order
model and SPARSE with the reference simulation in one dimension shows that both
the stress and the averaging of the carrier-phase velocity on the cloud subscale
affect the averaged motion of the particle. A three-dimensional isotropic
turbulence computation shows that only one computational parcel is sufficient to
accurately trace a cloud of tens of thousands of particles.
PMID- 28413342
TI - Identifying the significance of nonlinear normal modes.
AB - Nonlinear normal modes (NNMs) are widely used as a tool for understanding the
forced responses of nonlinear systems. However, the contemporary definition of an
NNM also encompasses a large number of dynamic behaviours which are not observed
when a system is forced and damped. As such, only a few NNMs are required to
understand the forced dynamics. This paper firstly demonstrates the complexity
that may arise from the NNMs of a simple nonlinear system-highlighting the need
for a method for identifying the significance of NNMs. An analytical
investigation is used, alongside energy arguments, to develop an understanding of
the mechanisms that relate the NNMs to the forced responses. This provides
insight into which NNMs are pertinent to understanding the forced dynamics, and
which may be disregarded. The NNMs are compared with simulated forced responses
to verify these findings.
PMID- 28413343
TI - G-Strands on symmetric spaces.
AB - We study the G-strand equations that are extensions of the classical chiral model
of particle physics in the particular setting of broken symmetries described by
symmetric spaces. These equations are simple field theory models whose
configuration space is a Lie group, or in this case a symmetric space. In this
class of systems, we derive several models that are completely integrable on
finite dimensional Lie group G, and we treat in more detail examples with
symmetric space SU(2)/S1 and SO(4)/SO(3). The latter model simplifies to an
apparently new integrable nine-dimensional system. We also study the G-strands on
the infinite dimensional group of diffeomorphisms, which gives, together with the
Sobolev norm, systems of 1+2 Camassa-Holm equations. The solutions of these
equations on the complementary space related to the Witt algebra decomposition
are the odd function solutions.
PMID- 28413344
TI - Analytical results regarding electrostatic resonances of surface phonon/plasmon
polaritons: separation of variables with a twist.
AB - The boundary integral equation (BIE) method ascertains explicit relations between
localized surface phonon and plasmon polariton resonances and the eigenvalues of
its associated electrostatic operator. We show that group-theoretical analysis of
the Laplace equation can be used to calculate the full set of eigenvalues and
eigenfunctions of the electrostatic operator for shapes and shells described by
separable coordinate systems. These results not only unify and generalize many
existing studies, but also offer us the opportunity to expand the study of
phenomena such as cloaking by anomalous localized resonance. Hence, we calculate
the eigenvalues and eigenfunctions of elliptic and circular cylinders. We
illustrate the benefits of using the BIE method to interpret recent experiments
involving localized surface phonon polariton resonances and the size scaling of
plasmon resonances in graphene nanodiscs. Finally, symmetry-based operator
analysis can be extended from the electrostatic to the full-wave regime. Thus,
bound states of light in the continuum can be studied for shapes beyond spherical
configurations.
PMID- 28413345
TI - Modelling damped acoustic waves by a dissipation-preserving conformal symplectic
method.
AB - We propose a novel stable and efficient dissipation-preserving method for
acoustic wave propagations in attenuating media with both correct phase and
amplitude. Through introducing the conformal multi-symplectic structure, the
intrinsic dissipation law and the conformal symplectic conservation law are
revealed for the damped acoustic wave equation. The proposed algorithm is exactly
designed to preserve a discrete version of the conformal symplectic conservation
law. More specifically, two subsystems in conjunction with the original damped
wave equation are derived. One is actually the conservative Hamiltonian wave
equation and the other is a dissipative linear ordinary differential equation
(ODE) system. Standard symplectic method is devoted to the conservative system,
whereas the analytical solution is obtained for the ODE system. An explicit
conformal symplectic scheme is constructed by concatenating these two parts of
solutions by the Strang splitting technique. Stability analysis and convergence
tests are given thereafter. A benchmark model in homogeneous media is presented
to demonstrate the effectiveness and advantage of our method in suppressing
numerical dispersion and preserving the energy dissipation. Further numerical
tests show that our proposed method can efficiently capture the dissipation in
heterogeneous media.
PMID- 28413346
TI - Rapidly convergent quasi-periodic Green functions for scattering by arrays of
cylinders-including Wood anomalies.
AB - This paper presents a full-spectrum Green-function methodology (which is valid,
in particular, at and around Wood-anomaly frequencies) for evaluation of
scattering by periodic arrays of cylinders of arbitrary cross section-with
application to wire gratings, particle arrays and reflectarrays and, indeed,
general arrays of conducting or dielectric bounded obstacles under both
transverse electric and transverse magnetic polarized illumination. The proposed
method, which, for definiteness, is demonstrated here for arrays of perfectly
conducting particles under transverse electric polarization, is based on the use
of the shifted Green-function method introduced in a recent contribution (Bruno &
Delourme 2014 J. Computat. Phys.262, 262-290 (doi:10.1016/j.jcp.2013.12.047)). A
certain infinite term arises at Wood anomalies for the cylinder-array problems
considered here that is not present in the previous rough-surface case. As shown
in this paper, these infinite terms can be treated via an application of ideas
related to the Woodbury-Sherman-Morrison formulae. The resulting approach, which
is applicable to general arrays of obstacles even at and around Wood-anomaly
frequencies, exhibits fast convergence and high accuracies. For example, a few
hundreds of milliseconds suffice for the proposed approach to evaluate solutions
throughout the resonance region (wavelengths comparable to the period and
cylinder sizes) with full single-precision accuracy.
PMID- 28413347
TI - A biochemo-mechano coupled, computational model combining membrane transport and
pericellular proteolysis in tissue mechanics.
AB - We present a computational model for the interaction of surface- and volume-bound
scalar transport and reaction processes with a deformable porous medium. The
application in mind is pericellular proteolysis, i.e. the dissolution of the
solid phase of the extracellular matrix (ECM) as a response to the activation of
certain chemical species at the cell membrane and in the vicinity of the cell. A
poroelastic medium model represents the extra cellular scaffold and the
interstitial fluid flow, while a surface-bound transport model accounts for the
diffusion and reaction of membrane-bound chemical species. By further modelling
the volume-bound transport, we consider the advection, diffusion and reaction of
sequestered chemical species within the extracellular scaffold. The chemo
mechanical coupling is established by introducing a continuum formulation for the
interplay of reaction rates and the mechanical state of the ECM. It is based on
known experimental insights and theoretical work on the thermodynamics of porous
media and degradation kinetics of collagen fibres on the one hand and a damage
like effect of the fibre dissolution on the mechanical integrity of the ECM on
the other hand. The resulting system of partial differential equations is solved
via the finite-element method. To the best of our knowledge, it is the first
computational model including contemporaneously the coupling between (i)
advection-diffusion-reaction processes, (ii) interstitial flow and deformation of
a porous medium, and (iii) the chemo-mechanical interaction impelled by the
dissolution of the ECM. Our numerical examples show good agreement with
experimental data. Furthermore, we outline the capability of the methodology to
extend existing numerical approaches towards a more comprehensive model for
cellular biochemo-mechanics.
PMID- 28413348
TI - Biofriendly nanocomposite containers with inhibition properties for the
protection of metallic surfaces.
AB - An attempt to combine two 'green' compounds in nanocomposite microcontainers in
order to increase protection properties of waterborne acryl-styrene copolymer
(ASC) coatings has been made. N-lauroylsarcosine (NLS) served as a corrosion
inhibitor, and linseed oil (LO) as a carrier-forming component. LO is compatible
with this copolymer and can impart to the coating self-healing properties. For
the evaluation of the protective performance, three types of coatings were
compared. In the first two, NLS was introduced in the coating formulation in the
forms of free powder and micro-containers filled with LO, correspondingly. The
last one was a standard ASC coating without inhibitor at all. Low-carbon steel
substrates were coated by these formulations by spraying and subjected
subsequently to the neutral salt spray test according to DIN ISO 9227. Results of
these tests as well as the data obtained by electrochemical study suggest that
such containers can be used for the improvement of adhesion of ASC-based coatings
to the substrate and for the enhancement of their protective performance upon
integrity damage, whereas the barrier properties of intact coatings were
decreased.
PMID- 28413349
TI - Comment on 'Are some people suffering as a result of increasing mass exposure of
the public to ultrasound in air?'
AB - A number of queries regarding the paper 'Are some people suffering as a result of
increasing mass exposure of the public to ultrasound in air?' (Leighton 2016
Proc. R. Soc. A472, 20150624 (doi:10.1098/rspa.2015.0624)) have been sent in from
readers, almost all based around some or all of a small set of questions. These
can be grouped into issues of engineering, human factors and timeliness. Those
issues (represented by the most typical wording used in queries) and my responses
are summarized in this comment.
PMID- 28413351
TI - Emerging surface characterization techniques for carbon steel corrosion: a
critical brief review.
AB - Carbon steel is a preferred construction material in many industrial and domestic
applications, including oil and gas pipelines, where corrosion mitigation using
film-forming corrosion inhibitor formulations is a widely accepted method. This
review identifies surface analytical techniques that are considered suitable for
analysis of thin films at metallic substrates, but are yet to be applied to
analysis of carbon steel surfaces in corrosive media or treated with corrosion
inhibitors. The reviewed methods include time of flight-secondary ion mass
spectrometry, X-ray absorption spectroscopy methods, particle-induced X-ray
emission, Rutherford backscatter spectroscopy, Auger electron spectroscopy,
electron probe microanalysis, near-edge X-ray absorption fine structure
spectroscopy, X-ray photoemission electron microscopy, low-energy electron
diffraction, small-angle neutron scattering and neutron reflectometry, and
conversion electron Moessbauer spectrometry. Advantages and limitations of the
analytical methods in thin-film surface investigations are discussed. Technical
parameters of nominated analytical methods are provided to assist in the
selection of suitable methods for analysis of metallic substrates deposited with
surface films. The challenges associated with the applications of the emerging
analytical methods in corrosion science are also addressed.
PMID- 28413350
TI - Mechanics of ultrasound elastography.
AB - Ultrasound elastography enables in vivo measurement of the mechanical properties
of living soft tissues in a non-destructive and non-invasive manner and has
attracted considerable interest for clinical use in recent years. Continuum
mechanics plays an essential role in understanding and improving ultrasound-based
elastography methods and is the main focus of this review. In particular, the
mechanics theories involved in both static and dynamic elastography methods are
surveyed. They may help understand the challenges in and opportunities for the
practical applications of various ultrasound elastography methods to characterize
the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties
of both bulk and thin-walled soft materials, especially the in vivo
characterization of biological soft tissues.
PMID- 28413352
TI - The Fourier decomposition method for nonlinear and non-stationary time series
analysis.
AB - for many decades, there has been a general perception in the literature that
Fourier methods are not suitable for the analysis of nonlinear and non-stationary
data. In this paper, we propose a novel and adaptive Fourier decomposition method
(FDM), based on the Fourier theory, and demonstrate its efficacy for the analysis
of nonlinear and non-stationary time series. The proposed FDM decomposes any data
into a small number of 'Fourier intrinsic band functions' (FIBFs). The FDM
presents a generalized Fourier expansion with variable amplitudes and variable
frequencies of a time series by the Fourier method itself. We propose an idea of
zero-phase filter bank-based multivariate FDM (MFDM), for the analysis of
multivariate nonlinear and non-stationary time series, using the FDM. We also
present an algorithm to obtain cut-off frequencies for MFDM. The proposed MFDM
generates a finite number of band-limited multivariate FIBFs (MFIBFs). The MFDM
preserves some intrinsic physical properties of the multivariate data, such as
scale alignment, trend and instantaneous frequency. The proposed methods provide
a time-frequency-energy (TFE) distribution that reveals the intrinsic structure
of a data. Numerical computations and simulations have been carried out and
comparison is made with the empirical mode decomposition algorithms.
PMID- 28413353
TI - Microprocessors: the engines of the digital age.
AB - The microprocessor-a computer central processing unit integrated onto a single
microchip-has come to dominate computing across all of its scales from the
tiniest consumer appliance to the largest supercomputer. This dominance has taken
decades to achieve, but an irresistible logic made the ultimate outcome
inevitable. The objectives of this Perspective paper are to offer a brief history
of the development of the microprocessor and to answer questions such as: where
did the microprocessor come from, where is it now, and where might it go in the
future?
PMID- 28413354
TI - Resistive-pulse and rectification sensing with glass and carbon nanopipettes.
AB - Along with more prevalent solid-state nanopores, glass or quartz nanopipettes
have found applications in resistive-pulse and rectification sensing. Their
advantages include the ease of fabrication, small physical size and needle-like
geometry, rendering them useful for local measurements in small spaces and
delivery of nanoparticles/biomolecules. Carbon nanopipettes fabricated by
depositing a thin carbon layer on the inner wall of a quartz pipette provide
additional means for detecting electroactive species and fine-tuning the current
rectification properties. In this paper, we discuss the fundamentals of resistive
pulse sensing with nanopipettes and our recent studies of current rectification
in carbon pipettes.
PMID- 28413355
TI - A computational continuum model of poroelastic beds.
AB - Despite the ubiquity of fluid flows interacting with porous and elastic
materials, we lack a validated non-empirical macroscale method for characterizing
the flow over and through a poroelastic medium. We propose a computational tool
to describe such configurations by deriving and validating a continuum model for
the poroelastic bed and its interface with the above free fluid. We show that,
using stress continuity condition and slip velocity condition at the interface,
the effective model captures the effects of small changes in the microstructure
anisotropy correctly and predicts the overall behaviour in a physically
consistent and controllable manner. Moreover, we show that the performance of the
effective model is accurate by validating with fully microscopic resolved
simulations. The proposed computational tool can be used in investigations in a
wide range of fields, including mechanical engineering, bio-engineering and
geophysics.
PMID- 28413356
TI - Propagation of combustion waves in the shell-core energetic materials with
external heat losses.
AB - In this paper, the properties and stability of combustion waves propagating in
the composite solid energetic material of the shell-core type are numerically
investigated within the one-dimensional diffusive-thermal model with heat losses
to the surroundings. The flame speed is calculated as a function of the
parameters of the model. The boundaries of stability are determined in the space
of parameters by solving the linear stability problem and direct integration of
the governing non-stationary equations. The results are compared with the
characteristics of the combustion waves in pure solid fuel. It is demonstrated
that a stable travelling combustion wave solution can exist for the parameters of
the model for which the flame front propagation is unstable in pure solid fuel
and it can propagate several times faster even in the presence of significant
heat losses.
PMID- 28413357
TI - Introduction for perspectives in geophysical and astrophysical fluids.
PMID- 28413358
TI - The soft computing-based approach to investigate allergic diseases: a systematic
review.
AB - BACKGROUND: Early recognition of inflammatory markers and their relation to
asthma, adverse drug reactions, allergic rhinitis, atopic dermatitis and other
allergic diseases is an important goal in allergy. The vast majority of studies
in the literature are based on classic statistical methods; however, developments
in computational techniques such as soft computing-based approaches hold new
promise in this field. OBJECTIVE: The aim of this manuscript is to systematically
review the main soft computing-based techniques such as artificial neural
networks, support vector machines, bayesian networks and fuzzy logic to
investigate their performances in the field of allergic diseases. METHODS: The
review was conducted following PRISMA guidelines and the protocol was registered
within PROSPERO database (CRD42016038894). The research was performed on PubMed
and ScienceDirect, covering the period starting from September 1, 1990 through
April 19, 2016. RESULTS: The review included 27 studies related to allergic
diseases and soft computing performances. We observed promising results with an
overall accuracy of 86.5%, mainly focused on asthmatic disease. The review
reveals that soft computing-based approaches are suitable for big data analysis
and can be very powerful, especially when dealing with uncertainty and poorly
characterized parameters. Furthermore, they can provide valuable support in case
of lack of data and entangled cause-effect relationships, which make it difficult
to assess the evolution of disease. CONCLUSIONS: Although most works deal with
asthma, we believe the soft computing approach could be a real breakthrough and
foster new insights into other allergic diseases as well.
PMID- 28413359
TI - Disulfide proteomics of rice cultured cells in response to OsRacl and probenazole
related immune signaling pathway in rice.
AB - BACKGROUND: Reactive oxygen species (ROS) production is an early event in the
immune response of plants. ROS production affects the redox-based modification of
cysteine residues in redox proteins, which contribute to protein functions such
as enzymatic activity, protein-protein interactions, oligomerization, and
intracellular localization. Thus, the sensitivity of cysteine residues to changes
in the cellular redox status is critical to the immune response of plants.
METHODS: We used disulfide proteomics to identify immune response-related redox
proteins. Total protein was extracted from rice cultured cells expressing
constitutively active or dominant-negative OsRacl, which is a key regulator of
the immune response in rice, and from rice cultured cells that were treated with
probenazole, which is an activator of the plant immune response, in the presence
of the thiol group-specific fluorescent probe monobromobimane (mBBr), which was a
tag for reduced proteins in a differential display two-dimensional gel
electrophoresis. The mBBr fluorescence was detected by using a charge-coupled
device system, and total protein spots were detected using Coomassie brilliant
blue staining. Both of the protein spots were analyzed by gel image software and
identified using MS spectrometry. The possible disulfide bonds were identified
using the disulfide bond prediction software. Subcellular localization and
bimolecular fluorescence complementation analysis were performed in one of the
identified proteins: Oryza sativa cold shock protein 2 (OsCSP2). RESULTS: We
identified seven proteins carrying potential redox-sensitive cysteine residues.
Two proteins of them were oxidized in cultured cells expressing DN-OsRac1, which
indicates that these two proteins would be inactivated through the inhibition of
OsRac1 signaling pathway. One of the two oxidized proteins, OsCSP2, contains 197
amino acid residues and six cysteine residues. Site-directed mutagenesis of these
cysteine residues revealed that a Cys140 mutation causes mislocalization of a
green fluorescent protein fusion protein in the root cells of rice. Bimolecular
fluorescence complementation analysis revealed that OsCSP2 is localized in the
nucleus as a homo dimer in rice root cells. CONCLUSIONS: The findings of the
study indicate that redox-sensitive cysteine modification would contribute to the
immune response in rice.
PMID- 28413360
TI - The CD31 molecule: a possible neuroprotective agent in acute ischemic stroke?
AB - BACKGROUND: The transmembrane receptor molecule CD31 is known to have
immunomodulatory functions, suggesting a possible neuroprotective effect in the
context of acute ischemic stroke by restricting an over-activation of secondary
immunological processes. This study examines the density of CD31+ cells in
mechanically extracted thrombi of stroke patients with the aim to test whether
the occurrence of CD31+ cells was associated with a beneficial clinical outcome
in those patients. METHODS: Thrombi of 122 consecutive patients with large
anterior circulation stroke were collected during intracranial mechanical
recanalization. Out of these, 86 immunostained specimens of adequate quality
could be analysed. The density of CD31+ cells was quantified and compared with
clinical outcome data of the affected patients. RESULTS: The density of CD31+
cells was positively related to early patient improvement (DeltaNIHSS, r = 0.283,
p = 0,012) with an even clearer relationship after exclusion of patients who died
in the early hospital phase (r = 0.371, p = 0.001). This finding stayed stable
also in the multivariate analysis after corrrection for other outcome-influencing
factors (p = 0.049). CONCLUSION: This study shows a stable relation between CD31+
cells and early clinical improvement of patients with acute ischemic stroke. This
finding is in line with recent reports showing immunomodulatory and potential
neuroprotective effects of CD31, suggesting that CD31 may be a promising
neuroprotective agent in stroke patients.
PMID- 28413361
TI - Cost-effectiveness analysis of the national decentralization policy of
antiretroviral treatment programme in Zambia.
AB - BACKGROUND: In resource-limited settings with a high prevalence of human
immunodeficiency virus (HIV) infection such as Zambia, decentralization of
HIV/acquired immunodeficiency syndrome (HIV/AIDS) treatment and care with
effective use of resources is a cornerstone of universal treatment and care.
OBJECTIVES: This research aims to analyse the cost effectiveness of the National
Mobile Antiretroviral Therapy (ART) Services Programme in Zambia as a means of
decentralizing ART services. METHODS: Cost-effectiveness analyses were performed
using a decision analytic model and Markov model to compare the original ART
programme, 'Hospital-based ART', with the intervention programme, Hospital-based
plus 'Mobile ART', from the perspective of the district government health office
in Zambia. The total cost of ART services, quality-adjusted life years (QALYs)
and incremental cost-effectiveness ratios (ICERs) were examined. RESULTS: The
mean annual per-patient costs were 1259.16 USD for the original programme and
2601.02 USD for the intervention programme, while the mean number of QALYs was
6.81 for the original and 7.27 for the intervention programme. The ICER of the
intervention programme relative to the original programme was 2965.17 USD/QALY,
which was much below the willingness-to-pay (WTP), or three times the GDP per
capita (4224 USD), but still over the GDP per capita (1408 USD). In the
sensitivity analysis, the ICER of the intervention programme did not
substantially change. CONCLUSION: The National Mobile ART Services Programme in
Zambia could be a cost-effective approach to decentralizing ART services into
rural areas in Zambia. This programme could be expanded to more districts where
it has not yet been introduced to improve access to ART services and the health
of people living with HIV (PLHIV) in rural areas.
PMID- 28413362
TI - Bone Loss in HIV Infection.
AB - Human immunodeficiency virus (HIV) infection is an established risk factor for
low bone mineral density (BMD) and subsequent fracture, and treatment with
combination antiretroviral therapy (cART) leads to additional BMD loss,
particularly in the first 1-2 years of therapy. The prevalence of low BMD and
fragility fracture is expected to increase as the HIV-infected population ages
with successful treatment with cART. Mechanisms of bone loss in the setting of
HIV infection are likely multifactorial, and include viral, host, and immune
effects, as well as direct and indirect effects of cART, particularly tenofovir
disoproxil fumarate (TDF) and the protease inhibitors (PIs). Emerging data
indicate that BMD loss following cART initiation can be mitigated by prophylaxis
with either long-acting bisphosphonates or vitamin D and calcium supplementation.
In addition, newer antiretrovirals, particularly the integrase strand transfer
inhibitors and tenofovir alafenamide (TAF), are associated with less intense bone
loss than PIs and TDF. However, further studies are needed to establish optimal
bone sparing cART regimens, appropriate screening intervals, and preventive
measures to address the rising prevalence of fragility bone disease in the HIV
population.
PMID- 28413363
TI - Wnt Signaling and Colorectal Cancer.
AB - The WNT signaling pathway is a critical mediator of tissue homeostasis and
repair, and frequently co-opted during tumor development. Almost all colorectal
cancers (CRC) demonstrate hyperactivation of the WNT pathway, which in many cases
is believed to be the initiating and driving event. In this short review, we
provide a focused overview of recent developments in our understanding of the WNT
pathway in CRC, describe new research tools that are enabling a deeper
understanding of WNT biology, and outline ongoing efforts to target this pathway
therapeutically.
PMID- 28413364
TI - Delivering Integrated Care to the Frail Elderly: The Impact on Professionals'
Objective Burden and Job Satisfaction.
AB - BACKGROUND: The impact of integrated working on professionals' objective burden
and job satisfaction was examined. An evidence-based intervention targeting frail
elderly patients was implemented in the Walcheren region of the Netherlands in
2010. The intervention involved the primary care practice as a single entry
point, and included proactive frailty screening, a comprehensive assessment of
patient needs, case management, multidisciplinary teams, care plans and
protocols, task delegation and task specialisation, a shared information system,
a geriatric care network and integrated funding. METHODS: A quasi-experimental
design with a control group was used. Data regarding objective burden involved
the professionals' time investments over a 12-month period that were collected
from patient medical records (n = 377) time registrations, transcripts of
meetings and patient questionnaires. Data regarding job satisfaction were
collected using questionnaires that were distributed to primary care and home
care professionals (n = 180) after the intervention's implementation. Within- and
between-groups comparisons and regression analyses were performed. RESULTS: Non
patient related time was significantly higher in the experimental group than in
the control group, whereas patient-related time did not differ. Job satisfaction
remained unaffected by the intervention. CONCLUSION AND DISCUSSION: Integrated
working is likely to increase objective burden as it requires professionals to
perform additional activities that are largely unrelated to actual patient care.
Implications for research and practice are discussed. [Current Controlled Trials
ISRCTN05748494].
PMID- 28413365
TI - Integrating the Principles of Evidence Based Medicine and Evidence Based Public
Health: Impact on the Quality of Patient Care and Hospital Readmission Rates in
Jordan.
AB - INTRODUCTION: Hospital readmissions impose not only an extra burden on health
care systems but impact patient health outcomes. Identifying modifiable
behavioural risk factors that are possible causes of potentially avoidable
readmissions can lower readmission rates and healthcare costs. METHODS: Using the
core principles of evidence based medicine and public health, the purpose of this
study was to develop a heuristic guide that could identify what behavioural risk
factors influence hospital readmissions through adopting various methods of
analysis including regression models, t-tests, data mining, and logistic
regression. This study was a retrospective cohort review of internal medicine
patients admitted between December 1, 2012 and December 31, 2013 at King Abdullah
University Hospital, in Jordan. RESULTS: 29% of all hospitalized patients were
readmitted during the study period. Among all readmissions, 44% were identified
as potentially avoidable. Behavioural factors including smoking, unclear follow
up and discharge planning, and being non-compliant with treatment regimen as well
as discharge against medical advice were all associated with increased risk of
avoidable readmissions. CONCLUSION: Implementing evidence based health programs
that focus on modifiable behavioural risk factors for both patients and
clinicians would yield a higher response in terms of reducing potentially
avoidable readmissions, and could reduce direct medical costs.
PMID- 28413367
TI - Discharge Planning: Screening Older Patients for Multidisciplinary Team Referral.
AB - The objective was to determine whether the Elders Risk Assessment Index can
predict multi-disciplinary team referral of older patients (>= 65 years) in
Emergency Department same-day discharges. The study identified 1,376 qualifying
individuals from a regional New Zealand hospital database. Of these, 12.7 % were
referred to the multi-disciplinary team. Univariate and multivariate analyses
were used to explore associations between the Index, its components, and other
demographic factors with referral. With every unit increase in the Index there
was a 9% increase in the odds of being referred. When the components of the Index
were analysed separately, an increased likelihood of being referred was
associated with not being married, having had a previous hospital admission of
more than five days, having chronic obstructive pulmonary disease, and being
older. Conversely, a decreased likelihood was associated with having diabetes.
When non-Index items were analysed it was found that females were more likely to
be referred than males and that Maori were less likely to be referred than New
Zealand Europeans. With adaptation, the Elders Risk Assessment Index may provide
a simple, cost-effective, and timely tool to assist in determining the need for
multi-disciplinary team referral for older people who present to the Emergency
Department.
PMID- 28413366
TI - Organizational Context and Capabilities for Integrating Care: A Framework for
Improvement.
AB - BACKGROUND: Interventions aimed at integrating care have become widespread in
healthcare; however, there is significant variability in their success.
Differences in organizational contexts and associated capabilities may be
responsible for some of this variability. PURPOSE: This study develops and
validates a conceptual framework of organizational capabilities for integrating
care, identifies which of these capabilities may be most important, and explores
the mechanisms by which they influence integrated care efforts. METHODS: The
Context and Capabilities for Integrating Care (CCIC) Framework was developed
through a literature review, and revised and validated through interviews with
leaders and care providers engaged in integrated care networks in Ontario,
Canada. Interviews involved open-ended questions and graphic elicitation.
Quantitative content analysis was used to summarize the data. RESULTS: The CCIC
Framework consists of eighteen organizational factors in three categories: Basic
Structures, People and Values, and Key Processes. The three most important
capabilities shaping the capacity of organizations to implement integrated care
interventions include Leadership Approach, Clinician Engagement and Leadership,
and Readiness for Change. The majority of hypothesized relationships among
organizational capabilities involved Readiness for Change and Partnering,
emphasizing the complexity, interrelatedness and importance of these two factors
to integrated care efforts. CONCLUSIONS: Organizational leaders can use the
framework to determine readiness to integrate care, develop targeted change
management strategies, and select appropriate partners with overlapping or
complementary profiles on key capabilities. Researchers may use the results to
test and refine the proposed framework, with a focus on the hypothesized
relationships among organizational capabilities and between organizational
capabilities and performance outcomes.
PMID- 28413368
TI - What Is Case Management? A Scoping and Mapping Review.
AB - The description of case management in research and clinical practice is highly
variable which impedes quality analysis, policy and planning. Case management
makes a unique contribution towards the integration of health care, social
services and other sector services and supports for people with complex health
conditions. There are multiple components and variations of case management
depending on the context and client population. This paper aims to scope and map
case management in the literature to identify how case management is described in
the literature for key complex health conditions (e.g., brain injury, diabetes,
mental health, spinal cord injury). Following literature searches in multiple
databases, grey literature and exclusion by health condition, community-based and
adequate description, there were 661 potential papers for data extraction. Data
from 79 papers (1988-2013) were analysed to the point of saturation (no new
information) and mapped to the model, components and activities. The results
included 22 definitions, five models, with 69 activities or tasks of case
managers mapped to 17 key components (interventions). The results confirm the
significant terminological variance in case management which produces role
confusion, ambiguity and hinders comparability across different health conditions
and contexts. There is an urgent need for an internationally agreed taxonomy for
the coordination, navigation and management of care.
PMID- 28413369
TI - Evaluation of Quality Indicators of Integrated Care in a Regional Psychiatry
Budget - A Pre-Post Comparison by Secondary Data Analysis.
AB - The Regional Psychiatry Budget (RPB), as a special arrangement within the German
Federal Hospital Refund Regulation, is based on the capitation principle. A lump
sum is allocated to a major inpatient care provider in a large region on a yearly
basis. Under this model, the provider is free to offer all forms of treatment and
to construct individual models of integrated care that specifically suit the
region and the needs of community members. The present study aimed to evaluate
selected aspects that represent a change in the psychiatric health status of
patients in the covered region under the conditions of the RPB. We performed a
secondary data analysis of administrative data of 19,913 cases generated by the
hospital in a pre-post comparison of the periods before and under RPB conditions.
The average length of an inpatient stay was reduced by approximately 22 % and
could be partially replaced by day care. Selected indicators suggest equal or
higher quality of care with stable cost in the population in need of psychiatric
care in the district.
PMID- 28413370
TI - Analysis of building deformation in landslide area using multisensor PSInSARTM
technique.
AB - Buildings are sensitive to movements caused by ground deformation. The mapping
both of spatial and temporal distribution, and of the degree of building damages
represents a useful tool in order to understand the landslide evolution,
magnitude and stress distribution. The high spatial resolution of space-borne SAR
interferometry can be used to monitor displacements related to building
deformations. In particular, PSInSAR technique is used to map and monitor ground
deformation with millimeter accuracy. The usefulness of the above mentioned
methods was evaluated in San Fratello municipality (Sicily, Italy), which was
historically affected by landslides: the most recent one occurred on 14th
February 2010. PSInSAR data collected by ERS 1/2, ENVISAT, RADARSAT-1 were used
to study the building deformation velocities before the 2010 landslide. The X
band sensors COSMO-SkyMed and TerraSAR-X were used in order to monitor the
building deformation after this event. During 2013, after accurate field
inspection on buildings and structures, damage assessment map of San Fratello
were created and then compared to the building deformation velocity maps. The
most interesting results were obtained by the comparison between the building
deformation velocity map obtained through COSMO-SkyMed and the damage assessment
map. This approach can be profitably used by local and Civil Protection
Authorities to manage the post-event phase and evaluate the residual risks.
PMID- 28413371
TI - The Synthesis of Novel Oxazolinylphosphinic Esters and Amides and Application to
the Cyanosilylation of Aldehydes.
AB - A new class of modular functionalized oxazolines are synthesized using a simple,
novel one-pot method under inert moisture-free conditions. Then the oxazolines
can be further elaborated to phosphine-containing oxazolines. The first step is
to synthesize intermediates via the reaction of 2 - hydroxybenzonitrile or 2
aminobenzonitrile with chiral amino alcohols, subsequent reactions with phosphine
chlorides, providing products in moderate yields. Product structures are fully
characterized by NMR, IR, MS and X-Ray analyses. These compounds are found to be
highly active catalysts for the cyanosilylation of prochiral benzaldehyde (20-96%
yield).
PMID- 28413372
TI - Electrochemical Impedance Spectroscopy Study of Concanavalin A Binding to Self
Assembled Monolayers of Mannosides on Gold Wire Electrodes.
AB - The interactions of the lectin Concanavalin A (Con A) with self-assembled
monolayers (SAMs) of thiolated mono-, di-, and tri-mannosides were studied on the
surface of gold wires using electrochemical impedance spectroscopy (EIS). The
SAMs of mannosides were prepared either pure or along with thiolated triethylene
glycol (TEG) at different molar ratios (1:1, 1:2, 1:4, 1:9, and 1:19) to better
understand and optimize the interaction conditions. The charge-transfer
resistance of the [Fe(CN)6]3-/4- redox probe was compared before and after the
interaction at different concentrations of Con A to determine the equilibrium
dissociation constant (Kd) and limit of detection (LOD). Values of Kd were found
in the nanomolar range showing multivalent interactions between mannosides and
Con A, and LOD was found ranging from 4-13 nM depending on the type of mannoside
SAM used. Analysis using the Hill equation suggests negative cooperativity in the
binding behavior. Peanut agglutinin was used as a negative control, and cyclic
voltammetry was used to further support the experiments. We have found that
neither the pure nor the widely dispersed monolayers of mannosides provide the
conditions for optimal binding of Con A. The binding of Con A to these SAMs is
sensitive to the molar ratio of the mannoside used to prepare the SAM and to the
structure of the mannoside. A simple cleaning method has also been shown to
regenerate the used gold wire electrodes. The results from these experiments
contribute to the development of simple, cheap, selective, and sensitive EIS
based bioassays, especially for lectin-carbohydrate interactions.
PMID- 28413373
TI - Electrochemical impedance spectroscopy study of carbohydrate-terminated
alkanethiol monolayers on nanoporous gold: Implications for pore wetting.
AB - Electrochemical impedance spectroscopy (EIS) is used to compare the apparent
electron transfer rate constant (kapp) for a series of alkanethiol and of
carbohydrate-terminated alkanethiol self-assembled monolayers (SAMs) on both flat
gold and on nanoporous gold (np-Au). Using the surface area for np-Au determined
by oxide stripping, the values of kapp for the alkanethiol modified np-Au are
initially over two orders of magnitude smaller than the values found on flat Au.
This result provides evidence that the diffusing redox probe Fe(CN)63-/4- only
accesses a fraction of the np-Au surface after alkanethiol modification
suggesting very limited wetting of the internal pores due to the hydrophobic
nature of these surfaces. In contrast, for np-Au modified by carbohydrate
terminated (mannose or galactose) alkanethiols the values of kapp are about 10-40
fold smaller than on flat gold, suggesting more extensive access of the diffusing
redox probe within the pores and better but still incomplete wetting, a result
also found for modification of np-Au with mercaptododecanoic acid. A short chain
PEG thiol derivative is found to result in a comparison of kapp values that
suggests nearly complete wetting of the internal pores for this highly
hydrophilic derivative. These results are of significance for the potential
applications of SAM modified np-Au in electrochemical sensors, especially for
those based on carbohydrate-protein recognition, or those of np-Au modified by
SAMs with polar terminal groups.
PMID- 28413374
TI - Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics.
AB - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common
cause of cancer-related death in Europe with a 5-year survival rate of <5%.
Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the
majority of cases malignancy is discovered too late for curative treatment. There
is at present no reliable diagnostic marker for PDAC available. OBJECTIVES: The
aim of the study was to identify single blood-based metabolites or a panel of
metabolites discriminating PDAC and CP using liquid chromatography-mass
spectrometry (LC-MS). METHODS: A discovery cohort comprising PDAC (n = 44) and CP
(n = 23) samples was analyzed by LC-MS followed by univariate (Student's t test)
and multivariate (orthogonal partial least squares-discriminant analysis (OPLS
DA)) statistics. Discriminative metabolite features were subject to raw data
examination and identification to ensure high feature quality. Their
discriminatory power was then confirmed in an independent validation cohort
including PDAC (n = 20) and CP (n = 31) samples. RESULTS: Glycocholic acid, N
palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers
discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of
five metabolites including the aforementioned three metabolites as well as
phenylacetylglutamine (PAGN) and chenodeoxyglycocholate. CONCLUSION: Using LC-MS
based metabolomics we identified three single metabolites and a five-metabolite
panel discriminating PDAC and CP in two independent cohorts. Although further
study is needed in larger cohorts, the metabolites identified are potentially of
use in PDAC diagnostics.
PMID- 28413376
TI - Ferromagnetic, folded electrode composite as a soft interface to the skin for
long-term electrophysiological recording.
AB - This paper introduces a class of ferromagnetic, folded, soft composite material
for skin-interfaced electrodes with releasable interfaces to stretchable,
wireless electronic measurement systems. These electrodes establish intimate,
adhesive contacts to the skin, in dimensionally stable formats compatible with
multiple days of continuous operation, with several key advantages over
conventional hydrogel based alternatives. The reported studies focus on aspects
ranging from ferromagnetic and mechanical behavior of the materials systems, to
electrical properties associated with their skin interface, to system-level
integration for advanced electrophysiological monitoring applications. The work
combines experimental measurement and theoretical modeling to establish the key
design considerations. These concepts have potential uses across a diverse set of
skin-integrated electronic technologies.
PMID- 28413375
TI - Inflammatory Cyclooxygenase Activity and PGE2 Signaling in Models of Alzheimer's
Disease.
AB - The inflammatory response is a fundamental driving force in the pathogenesis of
Alzheimer's disease (AD). In the setting of accumulating immunogenic Abeta
peptide assemblies, microglia, the innate immune cells of the brain, generate a
non-resolving immune response and fail to adequately clear accumulating Abeta
peptides, accelerating neuronal and synaptic injury. Pathological, biomarker, and
imaging studies point to a prominent role of the innate immune response in AD
development, and the molecular components of this response are beginning to be
unraveled. The inflammatory cyclooxygenase-PGE2 pathway is implicated in pre
clinical development of AD, both in epidemiology of normal aging populations and
in transgenic mouse models of Familial AD. The cyclooxygenase-PGE2 pathway
modulates the inflammatory response to accumulating Abeta peptides through
actions of specific E-prostanoid G-protein coupled receptors.
PMID- 28413378
TI - Is Age an Independent Factor for Prostate Cancer? A Paired Analysis.
AB - INTRODUCTION: Prostate cancer is the most prevalent malignant neoplasia among men
worldwide. Several prognostic factors, including Gleason's score, the measurement
of serum prostate-specific antigen (PSA) and the evaluation of the percentage of
fragments affected by cancer on prostate biopsy, have already been established.
Age alone, however, has yet to be studied as a prognostic factor independently
from other known factors. The aim of the present study was to compare the
characteristics and the evolution of prostate cancer in different age groups
using a paired analysis for patients with equivalent known prognostic factors. In
addition, we aimed to determine the true impact of age on the prognosis of
prostate cancer. MATERIAL AND METHODS: The data from 2,283 patients subjected to
radical retropubic prostatectomy between 1998 and 2009 were reviewed. The
patients were divided into three age groups: < 55 years old, between 56 and 65
and > 65 years old. Each patient was matched to another patient in the other
groups who had the same PSA range (< 4.0, between 4.0 and 10.0 and > 10), Gleason
score on the surgical specimen and prognostic range of positive fragments in the
prostate biopsy (< 33%, between 34 and 50% and > 50%). After pairing, each group
consisted of 215 patients, who were compared using the biochemical recurrence of
the disease (PSA > 0.2), the interval for biochemical relapse, extra-capsular
invasion and invasion of the seminal vesicles or the lymph nodes. RESULTS. No
significant difference was observed between the groups regarding the frequency of
relapses, interval of relapse, extra-capsular invasion and invasion of the
seminal vesicles or lymph nodes. DISCUSSION: None of the studied factors were
affected by the age of the patients. Therefore, patients of different ages had
tumors with similar characteristics and behaviors. CONCLUSION: When assessed
separately, without the effects of the main prognostic factors, age does not
appear to be an independent prognostic factor for prostate cancer.
PMID- 28413379
TI - Effect of Microsurgical Subinguinal Varicocele Repair on Chronic Dull Scrotal
Pain in Men with Grade II-III Lesions.
AB - INTRODUCTION: We aimed to evaluate the effectiveness of microsurgical subinguinal
varicocele repair in patients with grade II-III lesions and chronic dull scrotal
pain. MATERIALS AND METHODS: A total of 29 patients with grade II-III varicocele
and chronic dull scrotal pain that had a microsurgical subinguinal varicocele
repair were included in the study. They were followed-up for 6-12 months
including pain assessment and scrotal examination. RESULTS: Of the 29 patients,
28 (97%) reported complete resolution of pain with no palpable varicocele on
scrotal examination. No cases of testicular atrophy or hydrocele formation were
reported. CONCLUSION: These results indicated that microsurgical varicocele
repair should be considered in patients with grade II-III lesions and chronic
dull scrotal pain.
PMID- 28413377
TI - Mimicry of Appendicitis Symptomatology in Congenital Anomalies and Diseases of
the Genitourinary System and Pregnancy.
AB - INTRODUCTION: Appendicitis is a prevailing cause of acute abdomen, but is often
difficult to diagnose due to its wide range of symptoms, anatomical variations,
and developmental abnormalities. Urological disorders of the genitourinary tract
may be closely related to appendicitis due to the close proximity of the appendix
to the genitourinary tract. This review provides a summary of the urological
complications and simulations of appendicitis. Both typical and urological
symptoms of appendicitis are discussed, as well as recommended diagnostic and
treatment methods. METHODS: Medline searches were conducted via PubMed in order
to incorporate data from the recent and early literature. RESULTS: Urological
manifestations of appendicitis affect the adrenal glands, kidney,
retroperitoneum, ureter, bladder, prostate, scrotum, and penis. Appendicitis in
pregnancy is difficult to diagnose due to variations in appendiceal position and
trimester-specific symptoms. Ultrasound, CT, and MRI are used in diagnosis of
appendicitis and its complications. Treatment of appendicitis may be done via
open appendectomy or laparoscopic appendectomy. In some cases, other surgeries
are required to treat urological complications, though surgery may be avoided
completely in other cases. CONCLUSION: Clinical presentation and complications of
appendicitis vary among patients, especially when the genitourinary tract is
involved. Appendicitis may mimic urological disorders and vice versa. Awareness
of differential diagnosis and proper diagnostic techniques is important in
preventing delayed diagnosis and possible complications. MRI is recommended for
diagnosis of pregnant patients. Ultrasound is preferred in patients exhibiting
typical symptoms.
PMID- 28413380
TI - Expression of Epidermal Growth Factor Receptor and Transforming Growth Factor
Alpha in Cancer Bladder: Schistosomal and Non-Schistosomal.
AB - INTRODUCTION: Overexpression of epidermal growth factor receptor (EGFR) has been
described in several solid tumors including bladder cancer. Transforming growth
factor alpha (TGFalpha) is frequently deregulated in neoplastic cells and plays a
role in the development of bladder cancer. TGFalpha-EGFR ligand-receptor
combination constitutes an important event in multistep tumorigenesis. METHODS:
This study was done on 30 bladder biopsies from patients with urothelial
carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control
bladder specimens. All were immuohistochemically stained with EGFR and TGFalpha
antibodies. RESULTS: EGFR and TGFalpha were over-expressed in higher grades and
late stages of bladder cancer. Moreover, they show higher expression in squamous
cell carcinoma compared to urothelial carcinoma and in schistosomal associated
lesions than in non-schistosomal associated lesions. CONCLUSION: EGFR and
TGFalpha could be used as prognostic predictors in early stage and grade of
bladder cancer cases, especially those with schistosomal association. In addition
they can help in selecting patients who can get benefit from anti-EGFR molecular
targeted therapy.
PMID- 28413381
TI - Delayed Cytoreductive Nephrectomy Following Three Years of Targeted Therapy for
Metastatic Renal Cell Carcinoma.
AB - We present a 55-year-old male, with good performance status who was diagnosed
with a case of metastatic renal cell carcinoma following a pathologic femur
fracture. Despite good performance status, multifocal metastases and poor
prognostic features portended a grim prognosis with predicted overall survival of
less than nine months. On initial presentation, he was excluded from
cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not
pursued as the primary tumor was to be left in situ. The patient was reconsidered
for cytoreductive nephrectomy after sustained response to fifth line targeted
therapies with shrinkage of tumor burden. The post-operative course was
uneventful and the patient was discharged home on postoperative day one.
Temsirolimus was resumed one week after surgery and the patient reported
returning to his normal activities at the two week follow-up visit. We highlight
important clinical features of metastatic renal cell carcinoma, the surgical
considerations for cytoreductive nephrectomy and the detailed multidisciplinary
care the patient received throughout this case report.
PMID- 28413382
TI - Angiomyolipoma with Epithelial Cysts Masquerading as a Cystic Renal Cell
Carcinoma.
AB - Angiomyolipoma with epithelial cysts (AMLEC) is a very uncommon renal tumor.
AMLEC has a characteristic histological appearance and immunohistochemical
staining pattern, knowledge of which should preclude misdiagnosis by
pathologists. We present a rare case of an AMLEC which was suspected to be a
cystic renal cell carcinoma radiologically. We describe the characteristic
immunological staining pattern and ultrastructural features of this lesion and
discuss the potential differential diagnoses.
PMID- 28413384
TI - Pyogenic Granuloma of the Penis: An Uncommon Lesion with Unusual Presentation.
AB - We present the case of a 37-year-old man who presented with a penile lesion that
engorged on erection. Ultrasound examination demonstrated vascularity of the
lesion and the decision was made to perform a complete excision. Histological
analysis confirmed the diagnosis of a pyogenic granuloma of the penis. Follow-up
demonstrated no recurrence at 3 months.
PMID- 28413383
TI - Prostate Cancer: How Young is too Young?
AB - Prostate cancer is the most common non-cutaneous malignancy in men. It is
generally considered a cancer of the elderly, and the median age of presentation
is 68 years. However 10% of new diagnoses in the USA occur in men aged <= 55
years. This may be due to more prevalent screening nowadays, and may also reflect
the diagnosis of an increasingly recognized but underappreciated entity, i.e.
early-onset prostate cancer. Patients with early onset prostate cancer pose
unique challenges. Current data suggest that early-onset prostate cancer is a
distinct phenotype-from both an etiological and clinical perspective- that
deserves further attention. We present a case of a 28-year-old man who presented
with lower urinary tract symptoms and was diagnosed with advanced stage prostate
cancer.
PMID- 28413385
TI - Calciphylaxis Presenting with Various Symptoms: A Case Report.
AB - Calciphylaxis causes ischemia in multiple organs and skin ulcers owing to
progressive calcification in small and medial arteries. It has a poor prognosis
and often occurs in patients with hyperparathyroidism associated with end-stage
renal failure and those undergoing hemodialysis. Here, we present a case of
calciphylaxis associated with a wide range of symptoms, including lower thigh
skin ulcers, a rectovaginal fistula, and femoral neck fracture. The patient
underwent multiple treatments. However, she eventually died of cardiac failure.
PMID- 28413386
TI - Severe, Malignant Acanthosis Nigricans Associated with Adenocarcinoma of the
Endometrium in a Young Obese Female.
AB - Acanthosis nigricans (AN) is a dermatopathy associated with insulin-resistance,
drugs, endocrine disorders, chromosomal abnormalities (benign AN), and neoplasia
(malignant AN). Malignant AN (MAN) is a rare paraneoplastic skin syndrome most
commonly associated with gastric adenocarcinoma and other intra-abdominal
malignancies. We report the case of a 28-year-old female with AN associated with
obesity, insulin resistance, and endometrial adenocarcinoma. Although rare, MAN
is often an initial sign of malignancy and must trigger extensive investigation,
particularly in patients with sudden development of possibly paraneoplastic
dermatoses or in patients diagnosed with benign AN with any atypical features.
PMID- 28413387
TI - Successful Treatment of a Bullous Pemphigoid Patient with Rituximab Who Was
Refractory to Corticosteroid and Omalizumab Treatments.
AB - Omalizumab is a humanized monoclonal antibody which is an FDA-approved treatment
of severe allergic asthma and inhibits IgE binding to FcepsilonRI. According to
increasing evidence of IgE inhibition, omalizumab was suggested as a therapeutic
approach for bullous pemphigoid (BP). Rituximab has been reported to be effective
in various autoimmune diseases, including autoimmune bullous dermatoses. A
specific protocol for the use of rituximab to treat BP patients is not yet
available. There are only small case series and case reports about the efficacy
and safety of rituximab in BP. Here we present a young BP patient who responded
well to rituximab therapy and was refractory to conventional and omalizumab
therapies although he had elevated IgE levels and eosinophilia. Our case supports
the knowledge about the effectiveness and safety of rituximab not only in
pemphigus but also in BP. On the other hand, although it did not work in our
case, omalizumab may be a potentially effective agent in some carefully selected
patients with certain subtypes of BP.
PMID- 28413388
TI - A Case Report of Cushing's Disease Presenting as Hair Loss.
AB - Cushing's syndrome is a rare endocrine disorder that comprises a large group of
signs and symptoms resulting from chronic exposure to excess corticosteroids.
Most cases of Cushing's syndrome are due to increased adrenocorticotropic hormone
production from a pituitary adenoma, which is referred to as Cushing's disease.
Most of the signs and symptoms are nonspecific and common in the general
population, making a diagnosis often challenging. However, several dermatological
manifestations, such as fragile skin, easy bruising, and reddish purple striae,
are more discriminatory. Because uncontrolled Cushing's syndrome of any etiology
is associated with substantial morbidity, including increased cardiovascular
disease and mortality, it is important to make an early diagnosis. Unfortunately,
median delays of 2 years to diagnosis have been reported. We report a case of a
woman who had multiple dermatological findings, including facial plethora, easy
bruising, violaceous striae, hirsutism, and acne, the latter 2 signs reflecting
androgen excess. Of interest, our patient presented with a chief complaint of
hair loss, a common complaint in the general population that occurs with a
greater frequency in patients with Cushing's disease and is attributed to
androgenetic alopecia, but it is rarely the presenting symptom.
PMID- 28413389
TI - A Case of Right Atrial Obliteration Caused by Intracardiac Extension of
Hepatocellular Carcinoma.
AB - As the fifth most common malignancy worldwide, hepatocellular carcinoma (HCC) is
a frequently encountered clinical entity. Symptomatology associated with the
diagnosis includes hepatic dysfunction and pain from capsular spread.
Additionally, due to its propensity for vascular spread, extrahepatic
intravascular involvement can also be seen. We present a unique case of
intracardiac involvement of HCC. Originally diagnosed as acute on chronic heart
failure, echocardiography revealed the symptom source - tumor obliteration of the
right atrium. Clinical case presentation and management, along with radiographic
images are presented. A review of the current literature highlights this uncommon
presentation and the need for clinical suspicion of cardiac involvement in
patients with a history of HCC presenting with heart failure.
PMID- 28413390
TI - A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic
Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous
Neoplasm: A Case Report.
AB - Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms,
most of which are benign and do not communicate with the pancreatic duct.
Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal
adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year
old Japanese woman presented with a 10-mm multilocular cystic lesion at the
pancreatic body. Magnetic resonance pancreatography showed stenosis of the main
pancreatic duct at the pancreatic body and dilatation of the distal side of the
main pancreatic duct. Furthermore, communication between the cystic lesion and
the main pancreatic duct was suspected based on magnetic resonance
pancreatography findings. Distal pancreatectomy was performed under the
preoperative diagnosis of intraductal papillary mucinous neoplasm.
Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat
epithelium with clear cytoplasm and was thus diagnosed as a serous cystic
neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the
main and branch pancreatic ducts. Histological examination revealed no
communication between the serous cystic neoplasm and the pancreatic ducts.
Immunohistochemically, the epithelium of the serous cystic neoplasm showed
positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the
PanIN showed negative staining. A serous cystic neoplasm coexisting with another
pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic
ducts coexists with a serous cystic neoplasm, as in this case, the lesion
clinically mimics an intraductal papillary mucinous neoplasm.
PMID- 28413391
TI - Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non
Small Cell Lung Adenocarcinoma.
AB - INTRODUCTION: While epidermal growth factor receptor (EGFR) inhibitors have
improved progression-free survival in patients with non-small cell lung cancer
(NSCLC), one of the most common adverse effects is papulopustular skin eruption,
which is frequently severe enough to be treated with oral minocycline or
doxycycline. CASE: We present a case of an 87-year-old man who developed a severe
papulopustular skin eruption secondary to erlotinib therapy for NSCLC. Control of
the eruption with 100 mg of minocycline twice daily for 8 months eventually led
to blue-gray skin hyperpigmentation. After 30 months, this side effect was
recognized as minocycline drug deposition, which was confirmed with skin biopsy.
DISCUSSION: Compliance with EGFR inhibitor therapy in NSCLC is often challenging
due to common side effects, most notably cutaneous skin eruptions. Treatment of
cutaneous toxicities is important to preserve patient compliance with targeted
cancer therapy. Use of minocycline to treat the most common cutaneous side effect
(papulopustular eruption) can in turn cause blue-black skin, eye, or tooth
discoloration that can nullify its benefits, resulting in suboptimal patient
adherence to cancer therapy. Although this adverse effect is well known in
dermatology literature as a risk when using minocycline to treat acne, rosacea,
or blistering disorders, it is less well documented in oncology literature. We
present this case to highlight the need for greater consideration of unique
patient characteristics in selecting an oral antibiotic as a treatment modality
for EGFR inhibitor skin toxicities.
PMID- 28413392
TI - T-Cell Lymphoma in a Patient with Neurofibromatosis Type 1 and AIDS.
AB - Neurofibromatosis type 1 (NF1) and AIDS are risk factors for the development of
malignant neoplasms, including hematological malignancies, such as non-Hodgkin
lymphoma. NF1 is an autosomal dominant disease that primarily manifests as cafe
au-lait spots, dermal neurofibromas, axillary and/or inguinal ephelides or
freckles, plexiform neurofibromas, Lisch nodules, and bone deformities. In this
report, we present a 38-year-old female patient with NF1 from childhood and AIDS
who developed peripheral T-cell lymphoma with good response to chemotherapeutic
treatment.
PMID- 28413393
TI - Circulating Tumor Cell Count Can Be a Useful Prognostic Factor in Lung Resection
via Cardiopulmonary Bypass.
AB - Tumor resection with cardiopulmonary bypass (CPB) remains controversial in the
field of oncology. Here, we present a 57-year-old male patient with locally
advanced squamous cell carcinoma. The tumor was located in the left hilum and
invaded the left atrium. Complete resection, left pneumonectomy combined with
partial left atrium resection, was achieved using CPB. We evaluated the
circulating tumor cell (CTC) counts, as a surrogate for micrometastasis, in
peripheral blood and the CPB circuit. Both CTC counts were 0, which could
indicate local disease without micrometastasis. CTC count may be a useful
indicator for tumor resection with CPB in lung cancer.
PMID- 28413394
TI - Significant Amelioration of Tracheal Stenosis following Lenvatinib in a Patient
Who Has Anaplastic Thyroid Carcinoma with Bronchomediastinal Infiltration: A Case
Report.
AB - BACKGROUND: Anaplastic thyroid carcinoma has an extremely poor prognosis, and no
known drugs have exhibited acceptable efficacy. In recent years, novel anticancer
tyrosine kinase inhibitors have been developed. We encountered a case of tracheal
stenosis due to mediastinal and tracheal infiltration of anaplastic carcinoma for
which lenvatinib exhibited remarkable effects; owing to this, airway management
could be performed, even though the patient's condition was considered critical.
CASE REPORT: A 55-year-old man presented with locally advanced anaplastic thyroid
carcinoma that was observed to have mediastinal infiltration. Tracheal stenosis
due to infiltration of the trachea occurred, and the condition of the patient
rapidly deteriorated. Radiation and chemotherapy consisting of cetuximab,
cisplatin, and fluorouracil were ineffective, but his tracheal stenosis was
relieved 2 weeks after initiation of lenvatinib, after which the patient could be
discharged. However, the lenvatinib was ineffective for his liver, bone, and
brain metastatic lesions, and the patient remained in a critical condition.
CONCLUSION: We encountered a case in which lenvatinib was effective for locally
advanced anaplastic thyroid carcinoma, leading to an improvement in quality of
life and a prolonged life. The drug was effective for the primary lesion, but
mixed efficacy was noted for distant metastatic lesions.
PMID- 28413395
TI - A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated
with Preoperative FOLFOX Chemotherapy Followed by Radical Subtotal Gastrectomy
and D2 Lymph Node Dissection.
AB - We report the case of a 73-year-old female who was diagnosed with advanced
gastric cancer. Esophagogastroduodenoscopy was used to diagnose Borrmann type 3
advanced gastric cancer located at the gastric antrum. A biopsy revealed poorly
differentiated adenocarcinoma. Abdominopelvic computed tomography (CT) and 18F
fluorodeoxyglucose positron emission tomography-CT (FDG-PET-CT) scans
demonstrated multiple lymph node metastases, including the para-aortic lymph
nodes. Systemic chemotherapy with 5-fluoruracil (5-FU), oxaliplatin, and
leucovorin (FOLFOX) was initiated. An abdominopelvic CT scan taken after 4 cycles
of chemotherapy showed improvement in the ulceroinfiltrative gastric lesion and
marked regression of several enlarged lymph nodes. Consequently, we performed a
subtotal gastrectomy with D2 lymphadenectomy. The postoperative histopathological
report was early gastric carcinoma with no lymph node metastasis in the 48
resected lymph nodes. Another 4 cycles of FOLFOX chemotherapy were performed
after surgery. A FDG-PET-CT scan taken 12 months postoperatively showed no
definite evidence of local recurrence or distant metastasis, and the previously
noted retroperitoneal lymph nodes had disappeared. A FDG-PET-CT taken 16 months
postoperatively showed multiple lymph node metastases, including the left
supraclavicular lymph node. Despite 8 cycles of secondary chemotherapy with 5-FU,
irinotecan, and leucovorin (FOLFIRI) and radiotherapy, the patient died 38 months
after the operation.
PMID- 28413396
TI - Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node
Metastasis of Unknown Primary Site: A Case Report.
AB - BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a pathological entity
arising in the salivary glands first described by Skalova et al. [Am J Surg
Pathol 2010;34: 599-608]. Here, we report the first case of MASC presenting as a
cervical lymph node metastasis of unknown primary site together with a brief
review of the literature. CASE REPORT: We present a 74-year-old male with a
painless lump in his left neck. Based on the fine-needle aspiration cytological
findings, a possible malignant tumor was suspected. No evidence of a primary
lesion was observed using imaging modalities including positron emission
tomography/computed tomography. The patient underwent an ipsilateral modified
radical neck dissection. Immunohistochemical staining showed that the neoplastic
cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene
was noted during fluorescence in situ hybridization, and the final
histopathological diagnosis was MASC. CONCLUSION: We encountered a MASC
presenting as a cervical lymph node metastasis of unknown primary site. No
adjuvant therapy was administered, and no local recurrence or metastatic disease
has been detected during a follow-up period of 9 months. This is the first case
report of MASC presenting as a cervical lymph node metastasis of unknown primary
site and suggests the new properties of MASC.
PMID- 28413397
TI - Primary Extranodal Diffuse Large B-Cell Lymphoma of the Prostate: A Case Report.
AB - We report a case of primary diffuse large B-cell lymphoma of the prostate in a 54
year-old Caucasian male who presented with urinary retention and benign prostatic
hyperplasia. We discuss the rare presentation of this disease and its
clinicopathologic features and review the literature for up-to-date information
on the diagnosis and clinical management. Despite the low incidence of lymphoma
involving the prostate gland, it should always be considered as part of the
differential diagnosis in cases of prostate gland enlargement with urinary tract
obstructive symptoms resistant to medical therapy. Treatment modalities for this
rare disease are also discussed.
PMID- 28413398
TI - Desmoid Fibromatosis of the Abdominal Wall: Surgical Resection and Reconstruction
with Biological Matrix Egis(r).
AB - Desmoid tumor is a rare monoclonal fibroblast proliferation that is regarded as
benign. The clinical management of desmoid tumors is very complex and requires a
multidisciplinary approach because of the unpredictable disease course. For those
cases localized in the anterior abdominal wall, symptomatic and unresponsive to
medical treatment, radical resection and reconstruction with a prosthetic device
are indicated. We present here a case of desmoid fibromatosis of the left
anterolateral abdominal wall with a marked increase of the mass that required a
large excision followed by reconstruction with biological matrix. The fact that
it can be incorporated in patient tissue without a fibrotic response and that it
can resist future infections, together with a very competetive price, made the
new collagen matrix Egis(r) our first choice.
PMID- 28413399
TI - HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1
Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th
Century.
AB - INTRODUCTION: At the onset of the 20th century, ancient clinical observations of
cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They
were reported from 1914 to 1960, but remained unexplained. In 1983, in San
Francisco, Calif., USA, cancer epidemics were related to infections by the human
immunodeficiency virus type 1 (HIV-1) known as AIDS disease. Yet since 1996, it
is known that HIV-1 strains are not the only ones involved. In Sub-Saharan
Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1) and genital
recurrent herpes simplex virus type 2 (HSV-2) appeared many times prior to
infection by HIV-1. CASE REPORTS: Data on these ancient medical observations
regarding African cancer epidemics can today be referred to as the relationship
between the unfortunate immune deficiency of herpes in Bantu populations and HIV
1 viral strains. For centuries, the Bantu populations dispersed in forests were
living in close proximity to chimpanzees infected by simian immunodeficiency
virus (SIV) and were exposed to SIV contamination which became HIV-1 in human
beings. Presently, these unexplained Bantu cancer epidemics can be linked to the
viral partnership of HSV-1/HSV-2 to HIV-1 strains. CONCLUSION: The key issue is
now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment
administered early during childhood to Bantu populations will offer a mean of
preventing herpes diseases related to HIV-1 infection and hence avoid cancer
epidemics.
PMID- 28413400
TI - Autonomic Dysregulation, Cognitive Impairment, and Symptoms of Psychosis as an
Unusual Presentation in an Anti-Aquaporin 4-Positive Patient.
AB - We present the unusual case of a patient with an aquaporin 4 antibody
seropositive neuromyelitis optica spectrum disorder who presented with autonomic
dysregulation, cognitive impairment, and symptoms of psychosis. Only a few
previous cases have been described with similar psychiatric symptoms. Brain MRI
showed an abnormal hyperintense T2 signal of the hypothalamus and, to a lesser
extent, a minor hyperintense signal of the right optic nerve. Her symptoms and MR
abnormalities improved after high-dose methylprednisolone.
PMID- 28413401
TI - Parkinsonism in Association with Dihydropteridine Reductase Deficiency.
AB - We report a 16-year-old man with disorders of tetrahydrobiopterin metabolism due
to dihydropteridine reductase (DHPR) deficiency. He revealed moderate mental
retardation, parkinsonism, and spastic paralysis with levodopa and 5
hydroxytryptophan (5-HTP) supplementation from the age of 2 months. Brain MRI
showed high intensity areas in bilateral frontal and posterior deep white matter
on fluid-attenuated inversion recovery (FLAIR). Coronal FLAIR image showed a high
signal in bilateral pyramidal tracts. Single photon computed tomography (SPECT)
imaging of the dopamine transporter was normal. This imaging indicates no
dopaminergic cell loss. Our patient had no motor fluctuations or dyskinesias.
Early diagnosis and replacement treatment might lead to a favorable outcome.
PMID- 28413402
TI - Paraneoplastic Peripheral Nervous System Manifestations of Renal Cell Carcinoma:
A Case Report and Review of the Literature.
AB - Neurologic symptoms secondary to a paraneoplastic syndrome may be the presenting
manifestation of a previously undiagnosed cancer, and alertness to these
syndromes may provide an opportunity for early detection and treatment of a
cancer. Paraneoplastic weakness is a rare manifestation of renal cell carcinoma
and may present with variable electrophysiological features. We present a case of
a patient with progressive weakness, sensory changes, and urinary retention, with
electrophysiological features suggestive of a complex peripheral nervous system
syndrome. Ultimately, a renal cell mass was detected and resected, resulting in
significant clinical improvement. We review the literature, cataloging the known
neurologic syndromes and antibodies associated with renal cell carcinoma. This
case highlights that paraneoplastic neurological disorders associated with RCC
can take on many features and provides a resource to practitioners for early
detection of a neurologic paraneoplastic syndrome arising from renal cell
carcinoma.
PMID- 28413404
TI - Yellow Pattern 577-nm Micropulse Laser: Treatment of Macular Edema from Radiation
Retinopathy - A Case Report.
AB - We report a case of a 60-year-old Asian male who developed radiation retinopathy
23 years after initial radiotherapy for nasopharyngeal carcinoma and was
successfully treated with yellow pattern 577-nm micropulse laser. Secondary
macular edema and visual acuity improved following a single treatment session
with minimal scarring. Yellow pattern micropulse laser is a safe and effective
treatment for macular edema secondary to radiation retinopathy.
PMID- 28413405
TI - Intravitreal Aflibercept in Recalcitrant Radiation Maculopathy due to External
Beam Radiotherapy for Nasopharyngeal Cancer: A First Case Report.
AB - PURPOSE: To present the safety and efficacy of intravitreal aflibercept (Eylea)
in a patient with radiation maculopathy secondary to external beam radiotherapy
for nasopharyngeal cancer unresponsive to other therapeutic options. METHODS: A
73-year-old female presented with decreased visual acuity in both eyes 18 months
after completing 47 external beam cycles of radiation for nasopharyngeal cancer.
On presentation, her best corrected visual acuity was 6/60 in the right eye and
counting fingers from 1 meter in the left eye. She received 5 bevacizumab
injections in the right eye and 7 bevacizumab injections in the left eye over the
last year without any improvement. A treatment with intravitreal injections of
aflibercept was recommended in both eyes. RESULTS: The patient received 3
intravitreal aflibercept injections (2 mg/0.05 mL) in each eye every 4 weeks. The
visual acuity improved from 6/60 to 6/12 in the right eye and from counting
fingers to 6/36 in the left eye. Biomicroscopy showed less exudates, hemorrhages,
and microaneurysms. Optical coherence tomography revealed reduced central retinal
thickness in both eyes after 1-3 intravitreal aflibercept injections. CONCLUSION:
Intravitreal aflibercept should be regarded a safe and effective treatment in
patients with recalcitrant macular edema due to radiation maculopathy.
PMID- 28413403
TI - Two Cases of Proliferative Diabetic Retinopathy with Marked Sheathing of the
Retinal Arteries following Vitrectomy.
AB - PURPOSE: The aim of this paper was to report 2 patients (3 eyes) with
proliferative diabetic retinopathy (PDR) who showed marked sheathing of the
retinal arterioles that was ultimately attributed to calcification following
vitrectomy. CASES: Case 1 involved a 65-year-old female with PDR who underwent
bilateral vitrectomy for traction retinal detachment. Postoperatively, bilateral
retinal redetachment (reRD) was observed. Sheathing of the retinal arterioles was
observed at the same time, yet was not apparent preoperatively. Case 2 involved a
71-year-old female with PDR who underwent vitrectomy for vitreous hemorrhage.
Postoperatively, reRD was observed, and fundus findings showed sheathing of the
retinal arterioles. In both patients, silicone oil tamponade and retinopexy were
performed at reoperation, but sheathing of the retinal arterioles persisted
postoperatively. Fluorescein fundus angiography showed that retinal blood flow
was maintained, and no vessel leakage occurred. In addition, no sheathing of the
retinal veins was observed. Optical coherence tomography (OCT) showed a higher
intensity for retinal arterioles with sheathing than for normal retinal
arterioles. CONCLUSION: Vessel sheathing in our 2 patients (3 eyes) differed from
the sheathing seen in vasculitis. Based on the hyperintensity on OCT, this
sheathing may have been due to retinal artery calcification induced by hypoxia
and inflammation associated with reRD.
PMID- 28413406
TI - A Change in Ocular Circulation after Photocoagulation for Retinopathy of
Prematurity in a Neonate.
AB - BACKGROUND: The dilation of veins and tortuosity of arteries that occur in
retinopathy of prematurity (ROP) are improved by therapy, and thus posttherapy
changes in ocular circulation are also conceivable. We report a case of ROP in
which we were able to measure the ocular circulation before and after
photocoagulation therapy, using a laser speckle flowgraphy (LSFG) system that is
modified for neonates. CASE REPORT: A female infant was born at 25 weeks'
gestation with a birth weight of 808 g. We performed photocoagulation in both
eyes at age 15 weeks, and we measured the ocular circulation with the "LSFG-baby"
system before and at 12 weeks after the photocoagulation treatment. We also
measured the mean blur rate (MBR) in the optic nerve head (ONH) and the relative
flow volume (RFV) in the retinal vessels, and we examined the change rates from
before to after treatment. The changing rate of the MBR-A (the mean of all
values) in the ONH in the right and left eyes was 76.5 and 98.5%, respectively.
The vascular RFV in the severe dilation and tortuosity quadrant also tended to
decrease. CONCLUSIONS: Photocoagulation improved the dilation of veins and
tortuosity of arteries and reduced the ocular blood flow in this neonate with
ROP. The LSFG-baby system effectively and directly revealed the optic nerve and
retinal blood vessels.
PMID- 28413407
TI - Ophthalmia Secondary to Cobra Venom Spitting in the Volta Region, Ghana: A Case
Report.
AB - PURPOSE: To report the first case of ophthalmia due to contact with cobra venom
in the Volta Region, Ghana. METHODS: An ointment containing vitamin A was applied
to treat the patient's unilateral defects in the corneal epithelium and the
consequent diminished visual acuity. RESULTS: Healing of the corneal epithelium
and improvement of visual acuity were observed after only 1 day. CONCLUSIONS:
This case suggests that consequences of cases of cobra venom spitting in the eyes
can be minimal if immediate treatment is provided.
PMID- 28413408
TI - Choroidal Nevus-Associated Neovascular Membrane Demonstrated by OCT Angiography.
AB - We present a case of choroidal nevus, complicated by a choroidal neovascular
membrane (CNV) that was detected by OCT angiography. Choroidal nevi are
relatively common intraocular tumors. The presence of subretinal and intraretinal
fluids can indicate that a CNV has occurred as a complication, warranting prompt
management. However, subretinal and intraretinal fluids are also documented in
nevi without CNV. OCT angiography may be of great help in determining whether
those fluids are associated or not with a CNV, therefore guiding therapy.
PMID- 28413409
TI - Self-Optical Coherence Tomography and Angiography.
AB - PURPOSE: To present a new concept of self-optical coherence tomography (OCT) and
self-OCT angiography. METHODS: The operator sits in the patient seat and
manipulates the instrument body via the joystick with the dominant hand, while
the dominant index is ready to press the capture button and while focusing on the
fixation target. One senior ophthalmologist judged various OCT machines for ease
of self-scan during a major ophthalmic convention. Separately, self-scans were
also captured using a single OCT machine by one senior ophthalmologist and 5
junior optometrists and the scans were analyzed for both centration and image
quality value (IQV), and compared to regular scans done by an operator. RESULTS:
Ten available OCT machines were tested for their ability to allow self-OCT.
Machines that had one or more features of auto-alignment, auto-focus, and auto
shoot were ideal for self-OCT or self-OCT angiography. Self-scans done by the
ophthalmologist (total 27 scans of right eye, mean IQV = 32.6, and 24 left eyes,
mean IQV = 37.3, done over 9 months) and 5 optometrists (total 24 scans, mean
34.8 done in one session) were comparable to scans (total 11, mean IQV = 38.1)
done by an operator for image quality. Decentration was very common in self-scans
of the macula (37% right eye and 46% left eye) versus 0% for scans of the right
eye done by an operator. CONCLUSIONS: Self-OCT scans of the macular region can be
done with good image quality but are often decentered. Advantages include
privacy, potential use by ophthalmic health professionals, airspace station
officers, and possible future home self-imaging of macula.
PMID- 28413410
TI - Eccentric Macular Hole after Pars Plana Vitrectomy for Idiopathic Macular Hole: A
Case Report.
AB - INTRODUCTION: Postoperative eccentric macular hole (MH) formation is an uncommon
complication after pars plana vitrectomy (PPV) with internal limiting membrane
(ILM) peeling for epiretinal membrane or MH treatment. Herein, we present a case
of eccentric MH formation after PPV with ILM peeling for MH. CASE DESCRIPTION: A
72-year-old female patient underwent 23-gauge PPV with ILM peeling for idiopathic
MH in her right eye. The visual acuity was 6/24 in the right eye. One week
postoperatively the retina was attached and the MH seemed to be closed, while
visual acuity was 6/12. One month after PPV, there was a single eccentric retinal
hole below the macula, which was detected at the fundoscopy and was confirmed by
OCT. The visual acuity was 6/9 and the patient referred no symptoms. No further
intervention was attempted, and at the 6-month follow-up the visual acuity and
the size of the eccentric MH remained stable. CONCLUSIONS: Eccentric MHs can
develop after PPV and are usually managed conservatively by observation.
PMID- 28413411
TI - Corrigendum: The Hog1 MAP Kinase Promotes the Recovery from Cell Cycle Arrest
Induced by Hydrogen Peroxide in Candida albicans.
AB - [This corrects the article on p. 2133 in vol. 7, PMID: 28111572.].
PMID- 28413412
TI - Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory
Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
AB - BACKGROUND/AIMS: In the quest for prevention or treatment, there is a need to
find early markers for preclinical dementia. This study observed memory clinic
patients with subjective cognitive impairment (SCI) and normal cognitive function
at baseline. The primary aim was to address SCI as a potential risk factor for
cognitive decline. The secondary aim was to address a potential relation between
(1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory
performance over the first 2 years of follow-up, with a possible cognitive
decline after 6 years. METHODS: Eighty-one patients (mean age 61 years) were
recruited from university memory clinics and followed up for 6 years. RESULTS:
Eighty-six percent of the cohort remained cognitively stable or improved, 9%
developed mild cognitive impairment, and only 5% (n = 4) developed dementia.
Regression analysis revealed that low levels of Abeta42 at baseline and memory
decline during the first 2 years predicted dementia. When combined, these
variables were associated with a 50% risk of developing dementia. CONCLUSIONS:
Cognitive stability for 86% of the cohort suggests that SCI is predominantly a
benign condition with regard to neuropathology. The low number of individuals who
developed dementia limits the generalizability of the results and discussion of
progression factors.
PMID- 28413413
TI - The Risk of Incident Mild Cognitive Impairment and Progression to Dementia
Considering Mild Cognitive Impairment Subtypes.
AB - BACKGROUND: It remains unclear how demographic and clinical characteristics are
related to the risk of incident mild cognitive impairment (MCI) by its subtypes.
Moreover, the contribution of the subtypes of incident MCI to the progression to
dementia remains puzzling. METHODS: We used data collected by the National
Alzheimer Coordinating Center. Our analysis sample included cognitively normal
subjects at baseline. The associations were examined using competing-risks
survival regression models and Cox proportional hazards models. RESULTS: About
16.3% of subjects developed incident MCI of whom 15.8% progressed to Alz-heimer
disease (overall mean follow-up of 4.3 years). The risk of incident amnestic MCI
(aMCI) was greater in subjects with 1 copy (subhazard ratio [SHR]: 1.23; 95% CI:
1.00-1.50) or 2 copies (SHR: 2.14; 95% CI: 1.49-3.05) of the APOE epsilon4 allele
than in those who had no epsilon4 allele. Multiple-domain aMCI patients were more
likely to progress to dementia than single-domain aMCI patients (hazard ratio:
2.14; 95% CI: 1.28-3.58). CONCLUSIONS: Cognitively normal subjects with an APOE
epsilon4 allele had a higher likelihood of developing aMCI and the MCI subtype
was associated with the dementia subtype. Our findings provide important
information about practical indicators for the prediction of cognitive decline.
PMID- 28413414
TI - Comedication and Treatment Length in Users of Acetylcholinesterase Inhibitors.
AB - BACKGROUND/AIMS: Reduced clinical effect on cognitive decline in dementia by
acetylcholinesterase inhibitors (AChEIs) may be due to concurrent use of drugs
with anticholinergic properties. The aim was to analyze the incidence of AChEI
use and comedication with drugs with anticholinergic properties and other
potential unfavorable effects. METHODS: A prospective study applying drug use
data from the Norwegian Prescription Database. Anticholinergic Drug Scale (ADS)
scores were used as a measure of overall anticholinergic burden. RESULTS:
Patients with high ADS scores were more frequently discontinuing treatment early.
Coprescribing of antipsychotics was strongly associated with early
discontinuation of AChEI treatment. CONCLUSION: Coprescribing with potentially
unfavorable medications was common. A high ADS score was associated with early
discontinuation of treatment.
PMID- 28413415
TI - Effects of Nursing Home Residency on Diabetes Care in Individuals with Dementia:
An Explorative Analysis Based on German Claims Data.
AB - AIMS: This claims data-based study compares the intensity of diabetes care in
community dwellers and nursing home residents with dementia. METHODS: Delivery of
diabetes-related medical examinations (DRMEs) was compared via logistic
regression in 1,604 community dwellers and 1,010 nursing home residents with
dementia. The intra-individual effect of nursing home transfer was evaluated
within mixed models. RESULTS: Delivery of DRMEs decreases with increasing care
dependency, with more community-living individuals receiving DRMEs. Moreover,
DRME provision decreases after nursing home transfer. CONCLUSION: Dementia
patients receive fewer DRMEs than recommended, especially in cases of higher care
dependency and particularly in nursing homes. This suggests lacking awareness
regarding the specific challenges of combined diabetes and dementia care.
PMID- 28413416
TI - Immunohistochemical Glomerular Expression of Phospholipase A2 Receptor in Primary
and Secondary Membranous Nephropathy: A Retrospective Study in an Indian Cohort
with Clinicopathological Correlations.
AB - BACKGROUND: Limited published literature exists on the utility and
standardization of anti-phospholipase A2 receptor (anti-PLA2R)
immunohistochemistry (IHC) for the diagnosis of primary membranous nephropathy
(MN). The study aimed to validate anti-PLA2R IHC for the diagnosis of primary MN
and clinicopathological correlations in an Indian cohort. METHODS: Subjects
included patients with primary and secondary MN diagnosed between January 2012
and August 2014 with an adequate renal biopsy and at least 1 year of clinical
follow-up. Anti-PLA2R IHC was performed in all cases with miscellaneous renal
lesions as controls. Electron microscopy was performed in selected cases.
Sensitivity and specificity of anti-PLA2R IHC to identify primary MN was
evaluated. Histopathological analyses of primary and secondary MN were done with
clinicopathological correlations including serum creatinine, eGFR, chronic kidney
disease stage, 24-h urine protein, serum cholesterol, serum albumin, and
hypertension at presentation and follow-up, using the Kruskal-Wallis test and
Spearman rank correlation. A p value of <=0.05 was considered statistically
significant. RESULTS: In 153 MN patients (99 primary, 54 secondary) and 37
miscellaneous controls, anti-PLA2R IHC differentiated primary from secondary MN
with a sensitivity of 70.2% and a specificity of 96.6%. Secondary MN had
increased mesangial matrix expansion compared to primary MN (p = 0.001). Severe
nephrotic syndrome, impaired renal function, and hypertension were all more
common in primary than in secondary MN. CONCLUSION: Anti-PLA2R IHC is a specific
marker to distinguish primary MN from secondary MN.
PMID- 28413417
TI - The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload.
AB - BACKGROUND: Fluid overload in patients on conventional hemodialysis is a frequent
complication, associated with increased cardiovascular morbidity and mortality.
The dialysate sodium prescription is a potential modifiable risk factor. Our
primary objective was to describe associations between dialysate-to-serum sodium
gradient and parameters of fluid status. A secondary objective was to evaluate
the 6-month risk of hospitalization and mortality in relation to sodium gradient.
METHODS: We performed a cross-sectional study of 110 prevalent conventional
hemodialysis patients at a single center. The associations of sodium gradient
with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and
blood pressure (BP) were analyzed. RESULTS: The mean serum sodium gradient was
4.6 +/- 3.6 mEq/L. There was a direct correlation between sodium gradient and
IDWG% (r = 0.48, p < 0.01) as well as UF rate (r = 0.44, p < 0.01). In a logistic
regression model, a 1 mEq/L higher sodium gradient was associated with increased
risk of IDWG% >3% (OR 1.33, p < 0.01) and increased risk of UF rate >10 mL/kg/h
(OR 1.16, p = 0.03), but there were no associations with intradialytic
hypotension, intradialytic hypertension or BP. No significant differences were
found with 6-month hospitalization or mortality risk in relation to sodium
gradient. CONCLUSION: A higher sodium gradient was associated with significant
increases in IDWG and UF rates, known to be associated with poor outcomes, but
was not associated with intradialytic hypotension. Individualizing the dialysate
sodium prescription to minimize sodium gap may lead to less fluid overload in
conventional hemodialysis patients.
PMID- 28413418
TI - Study of the regulatory promoter polymorphism (-938C>A) of B-cell lymphoma 2 gene
in breast cancer patients of Mazandaran province in Northern Iran.
AB - BACKGROUND: The incidence rate of breast cancer has been dramatically increasing
since the last decade in Iran, and it is now one of the most common female
malignant tumors. B-cell lymphoma 2 (BCL2) family is the most important regulator
of apoptosis, and -938C>A single nucleotide polymorphism (SNP) of BCL2 gene
promoter has been demonstrated to influence breast cancer susceptibility. In this
research, we study the effect of -938C>A allelic variants on breast cancer risk
in Mazandaran province at the North of Iran. MATERIALS AND METHODS: This analysis
performed on 120 breast cancer patients who underwent surgery in some referenced
hospitals at Mazandaran province along with 130 healthy individuals as a control.
DNA extracted from peripheral blood samples was applied in polymerase chain
reaction-single-strand conformation polymorphism analysis to determine -938C>A
genotype. The association of the -938C>A genotype and breast cancer risk as well
as clinicopathological characters were analyzed by logistic regression method.
RESULTS: Results showed that genotype frequency of AA, AC, and CC genotypes was
10%, 62%, and 28% for case and 28%, 50%, and 22% in control group, respectively.
In the logistic regression model, BCL2 - 938C/A variant genotype AA was
associated with a decreased risk of breast cancer (P = 0.041) by 0.31-fold (odds
ratio = 0.31, confidence interval = 0.091-0.909) compared to CC genotype.
However, no significant association found between -938C>A genotype and
clinicopathological characters. CONCLUSION: The study showed that AA genotype of
BCL2 gene (-938C>A) is associated with decreased susceptibility to breast cancer.
Hence, investigating the -938C>A SNP of BCL2 gene promoter could be an
appropriate molecular marker to determine individual sensitivity to breast
cancer.
PMID- 28413419
TI - Role of Vitamin D on glycemic control and oxidative stress in type 2 diabetes
mellitus.
AB - BACKGROUND: Vitamin D deficiency may play a key role in the development of
impaired glucose tolerance, type 2 diabetes mellitus (T2DM), and metabolic
syndrome. Several studies have shown that Vitamin D has an antioxidant property.
We aimed to investigate 25-hydroxy Vitamin D (25[OH]D) levels in patients with
T2DM and in nondiabetic healthy controls and to ascertain the impact of 25(OH)D
levels on glycemic control and oxidative stress in T2DM patients. MATERIALS AND
METHODS: Thirty male patients with T2DM and twenty age- and socioeconomic status
matched male healthy controls were included in the study. Fasting and
postprandial blood sugar and glycated hemoglobin (HbA1c) were measured. Enzyme
activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) was
determined by spectrophotometric assay, and serum levels of 25(OH)D were measured
using radioimmunoassay. RESULTS: Serum Vitamin D levels were significantly lower
in patients with T2DM than healthy controls (P = 0.015). There was a
significantly lower GPx activity in patients with T2DM than controls (P = 0.048),
but the difference in SOD activity did not reach statistical significance. There
was a significant negative correlation between serum Vitamin D levels and HbA1c
(P = 0.016), but no statistical correlation was shown between serum Vitamin D
levels and GPx and SOD. CONCLUSION: We conclude that low level of Vitamin D might
play a significant role in T2DM pathogenesis. Hence, Vitamin D supplementation
may improve glycemic control and oxidative stress in T2DM.
PMID- 28413420
TI - Overcrowding in emergency departments: A review of strategies to decrease future
challenges.
AB - Emergency departments (EDs) are the most challenging ward with respect to patient
delay. The goal of this study is to present strategies that have proven to reduce
delay and overcrowding in EDs. In this review article, initial electronic
database search resulted in a total of 1006 articles. Thirty articles were
included after reviewing full texts. Inclusion criteria were assessments of real
patient flows and implementing strategies inside the hospitals. In this study, we
discussed strategies of team triage, point-of-care testing, ideal ED patient
journey models, streaming, and fast track. Patients might be directed to
different streaming channels depending on clinical status and required
practitioners. The most comprehensive strategy is ideal ED patient journey
models, in which ten interrelated substrategies are provided. ED leaders should
apply strategies that provide a continuous care process without deeply depending
on external services.
PMID- 28413422
TI - Anesthetic approach to Niemann-Pick Type C patient for dental treatment.
PMID- 28413421
TI - The effect of Vitamin D and calcium plus Vitamin D on leg cramps in pregnant
women: A randomized controlled trial.
AB - BACKGROUND: This study intended to determine the effects of Vitamin D and calcium
Vitamin D in treating leg cramps in pregnant women. MATERIALS AND METHODS: This
study was conducted as a double-blind randomized controlled clinical trial on 126
participants, 18-35-year-old pregnant women with a minimum of two leg cramps per
week who were referred to health-care centers in Tabriz-Iran in 2013. The
participants were allocated to three 42 member groups using a randomized block
design. For 42 days, the intervention groups took a 1000 unit Vitamin D pill or
300 mg calcium carbonate plus a 1000 unit Vitamin D pill, and the control group
received a placebo pill every day. The participants were evaluated with regard to
the frequency, length, and pain intensity of leg cramps during the week before
and during the 3rd and 6th week of the intervention. The ANCOVA and repeated
measurement test were used to analyze the data. RESULTS: Results showed that
controlling for the effects before the intervention, calcium-Vitamin D, and
Vitamin D supplements had no effect on the frequency, length, and pain intensity
of leg cramps. CONCLUSION: The results of this study showed that the calcium
Vitamin D and the Vitamin D supplements have no effect on the frequency, length,
and pain intensity of leg cramps during the 6 weeks of the study.
PMID- 28413423
TI - Preconception care: A pragmatic approach for planned pregnancy.
PMID- 28413425
TI - Association of retinol-binding protein 4 with metabolic syndrome in first-degree
relatives of type 2 diabetic patients.
AB - BACKGROUND: Retinol-binding protein 4 (RBP4) is known to regulate lipid and
glucose metabolism and insulin resistance. The influences of RBP4 on metabolic
syndrome (MS) are still unclear. The purpose of this study is to evaluate the
association between serum levels of RBP4 and MS components in first-degree
relations of type 2 diabetic patients. MATERIALS AND METHODS: This cross
sectional study was performed within the framework of the diabetes prevention
project in Isfahan. This study has been conducted during 2012-2013. Seventy-eight
subjects participate, with an average age of 43.20 +/- 5.29 years. Weight,
height, waist and hip circumferences, blood pressure (BP) of participants,
fasting plasma glucose, hemoglobin A1c, total cholesterol, high-density
lipoprotein cholesterol, triglyceride (TG), and serum RBP4 were measured from
fasting blood sample taken from each participant after an overnight fast (12-14
h). RESULTS: Systolic and diastolic BP were significantly higher in people in top
median of RBP4 (11.8 +/- 1.5 vs. 11.0 +/- 1.2, P = 0.01 and 7.8 +/- 1.0 vs. 7.3
+/- 0.9, P = 0.03). Moreover, TG in people with high levels of RBP4 was higher
compared with those with low levels of RBP4 (177.7 +/- 97.6 vs. 138.7 +/- 56.9, P
= 0.02). People with low levels of RBP4 had significant greater hip
circumferences (107.9 +/- 7.5 vs. 104.3 +/- 8.0, P = 0.04). There was no
correlation between RBP4 and MS in crude model (odds ratio [OR]: 1.00, 0.95-1.05,
P = 0.97). This null correlation remained after adjustment for body mass index,
age, and physical activity (OR: 0.93, 0.91-1.07, P = 0.31). CONCLUSION: Although
RBP4 levels were positively association with some risk factors of MS including
hip circumference, TG, and systolic and diastolic BP, it does not seem to be a
valuable marker for identification of the MS in the first relative degree of
diabetic patients.
PMID- 28413426
TI - An inter-professional approach to personalized medicine education: one
institution's experience.
AB - Personalized medicine offers the promise of better diagnoses, targeted therapies
and individualized treatment plans. Pharmacogenomics is an integral component of
personalized medicine; it aids in the prediction of an individual's response to
medications. Despite growing public acceptance and emerging clinical evidence,
this rapidly expanding field of medicine is slow to be adopted and utilized by
healthcare providers, although many believe that they should be knowledgeable and
able to apply pharmacogenomics in clinical practice. Institutional infrastructure
must be built to support pharmacogenomic implementation. Multidisciplinary
education for healthcare providers is a critical component for pharmacogenomics
to achieve its full potential to optimize patient care. We describe our recent
experience at the Mayo Clinic implementing pharmacogenomics education in a large,
academic healthcare system facilitated by the Mayo Clinic Center for
Individualized Medicine.
PMID- 28413424
TI - Environmental factors influencing the risk of autism.
AB - Autism is a developmental disability with age of onset in childhood (under 3
years old), which is characterized by definite impairments in social
interactions, abnormalities in speech, and stereotyped pattern of behaviors. Due
to the progress of autism in recent decades, a wide range of studies have been
done to identify the etiological factors of autism. It has been found that
genetic and environmental factors are both involved in autism pathogenesis.
Hence, in this review article, a set of environmental factors involved in the
occurrence of autism has been collected, and finally, some practical
recommendations for reduction of the risk of this devastating disease in children
are represented.
PMID- 28413427
TI - Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F)
nanoparticle vaccine in older adults.
AB - BACKGROUND: A preventative strategy for Respiratory Syncytial Virus (RSV)
infection constitutes an under-recognized unmet medical need among older adults.
Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 MUg
RSV F protein, with or without aluminum phosphate adjuvant) administered
concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in
older adult subjects were evaluated for safety and immunogenicity in this
randomized, observer-blinded study. RESULTS: A total of 220 healthy males and
females >= 60 years of age, without symptomatic cardiopulmonary disease, were
vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine
formulations produced an acceptable safety profile, with no vaccine-related
serious adverse events or evidence of systemic toxicity. Vaccine-induced immune
responses were rapid, rising as early as 7 days post-vaccination; and were
comparable in all formulations in terms of magnitude, with maximal levels
attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak
anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect
observed at the 60 MUg dose, and a dose-effect observed between the unadjuvanted
60 and 90 MUg regimens. The anti-F response persisted through 12 months post
vaccination. Palivizumab-competitive antibodies were below quantifiable levels
(<33 MUg/mL) at day 0. The rise of antibodies with specificity for Site II
peptide, and the palivizumab-competitive binding activity, denoting antibodies
binding at, or in proximity to, antigenic Site II on the F protein, closely
paralleled the anti-F response. However, a larger proportion of antibodies in
adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0
neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in
response to vaccination. Importantly, the RSV F vaccine co-administered with TIV
did not impact the serum hemagglutination inhibition antibody responses to a
standard-dose TIV, and TIV did not impact the immune response to the RSV F
vaccine. CONCLUSIONS: RSV F protein nanoparticle vaccine induced increases in
measures of functional immunity to RSV in older adults and demonstrated an
acceptable safety profile. Adjuvanted formulations provided additional
immunogenicity benefit as compared to increasing antigen dose alone. This trial
was registered with ClinicalTrials.gov number NCT01709019.
PMID- 28413428
TI - Transcriptomic evidence of a para-inflammatory state in the middle aged lumbar
spinal cord.
AB - BACKGROUND: We have previously reported elevated expression of multiple pro
inflammatory markers in the lumbar spinal cord (LSC) of middle-aged male rats
compared to young adults suggesting a para-inflammatory state develops in the LSC
by middle age, a time that in humans is associated with the greatest pain
prevalence and persistence. The goal of the current study was to examine the
transcriptome-wide gene expression differences between young and middle aged LSC.
METHODS: Young (3 month) and middle-aged (17 month) naive Fisher 344 rats (n = 5
per group) were euthanized, perfused with heparinized saline, and the LSC were
removed. RESULTS: ~70% of 31,000 coding sequences were detected. After
normalization, ~ 1100 showed statistically significant differential expression.
Of these genes, 353 middle-aged annotated genes differed by > 1.5 fold compared
to the young group. Nearly 10% of these genes belonged to the microglial sensome.
Analysis of this subset revealed that the principal age-related differential
pathways populated are complement, pattern recognition receptors, OX40, and
various T cell regulatory pathways consistent with microglial priming and T cell
invasion and modulation. Many of these pathways substantially overlap those
previously identified in studies of LSC of young animals with chronic
inflammatory or neuropathic pain. CONCLUSIONS: Up-modulation of complement
pathway, microglial priming and activation, and T cell/antigen-presenting cell
communication in healthy middle-aged LSC was found. Taken together with our
previous work, the results support our conclusion that an incipient or para
inflammatory state develops in the LSC in healthy middle-aged adults.
PMID- 28413429
TI - Falling under the umbrella cells: A single institutional experience and
literature review of urothelial carcinoma presenting as a primary pancreatic mass
on endoscopic ultrasound-guided fine-needle aspiration.
AB - Metastases to the pancreas are much less common than primary pancreatic lesions,
and there are few reports in the literature of metastatic urothelial carcinoma
(UC) found in the pancreas. We report two cases of metastatic UC mimicking a
primary pancreatic lesion. Two female patients, aged 48 and 83 years, presented
with isolated pancreatic lesions causing obstructive jaundice suspicious for
pancreatic adenocarcinoma and underwent endoscopic ultrasound-guided fine-needle
aspiration (EUS-FNA) with rapid on-site evaluation (ROSE). On cytopathology, the
lesions were found to be UC, confirmed with immunohistochemical (IHC) staining.
UC rarely metastasizes to the pancreas, and diagnosis through EUS-FNA can be
challenging. However, the utilization of ROSE, dedicated cell block passes, and
IHC have proved to be effective in obtaining this unusual pancreatic diagnosis by
EUS-FNA.
PMID- 28413430
TI - Next-generation sequencing of non-small cell lung cancer using a customized,
targeted sequencing panel: Emphasis on small biopsy and cytology.
AB - BACKGROUND: Next-generation sequencing (NGS) with a multi-gene panel is now
available for patients with lung adenocarcinoma, but the performance
characteristics and clinical utility of this testing are not well-described. We
present the results of an extended 467 gene panel in a series of advanced, highly
selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens,
including predominantly small biopsy and cytology specimens. MATERIALS AND
METHODS: A retrospective review of 22 NSCLC biopsies sent for NGS using an
extended gene panel from January 2014 to July 2015. The customized NGS panel
sequences 467 cancer-associated genes with exonic and intronic sequences obtained
from purified tumor DNA. Genomic alterations, patient characteristics, and
success of testing were determined. RESULTS: The majority of samples tested were
metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5
(22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology
specimens. Twenty-one (95%) of the specimens were adequate for full sequencing
and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which
17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic
alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2,
KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes.
CONCLUSIONS: NGS using a comprehensive gene panel was performed successfully in
95% of all NSCLC cases in this series, including 94% small biopsy and cytology
specimens and 100% surgical resections. This custom assay was performed on a
range of tumor specimens and demonstrates that small specimens are able to
provide a similar depth of information as larger ones. As many patients present
at an advanced stage and only small specimens are obtained, the information these
provide has the potential for guiding treatment in highly selected patients with
advanced lung adenocarcinoma.
PMID- 28413432
TI - Resveratrol regulates body weight in healthy and ovariectomized rats.
AB - OBJECTIVE: The elevated body weight in post-menopausal state attributes to the
reduced estrogen levels which is alleviated by resveratrol (RES) but its role in
control rats is not well understood. The main objective of the study was to
explore the effects of RES on the body weight of ovariectomized (OVX) female rats
with controls and to relate their biochemical parameters. METHODS: Female Wistar
rats weighing 200-300 g underwent bilateral ovariectomy (OVX) and were fed soya
free diet (n = 8 rats per group). In all groups: (Control, Control + Resveratrol,
OVX and OVX + Resveratrol) resveratrol was administered orally at a dose of 5
mg/kg/day for 1 month. Glucose and other biochemical parameters were examined.
RESULTS: Significant reduction in the gain of body weight was observed in the
control rats treated with resveratrol. Ovariectomy caused an escalation in gain
of body weight due to loss of estrogen which was brought down with resveratrol.
There was a slight dip in the blood glucose levels after resveratrol treatment.
CONCLUSION: Resveratrol significantly reduced the gain of body weight in the
control rats and in OVX rats showing its antiobesogenic effects.
PMID- 28413431
TI - Asian house rats may facilitate their invasive success through suppressing brown
rats in chronic interaction.
AB - BACKGROUND: The Asian house rat (Rattus tanezumi) and the brown rat (Rattus
norvegicus) are closely related species and are partially sympatric in southern
China. Over the past 20 years, R. tanezumi has significantly expanded northward
in China and partially replaced the native brown rat subspecies, R. n.
humiliatus. Although invasive species are often more aggressive than native
species, we did not observe interspecific physical aggression between R. tanezumi
and R. n. humiliatus. Here, we focused on whether or not R. tanezumi was superior
to R. n. humiliatus in terms of nonphysical competition, which is primarily
mediated by chemical signals. RESULTS: We performed two laboratory experiments to
test different paradigms in domesticated R. tanezumi and R. n. humiliatus. In
Experiment 1, we caged adult male rats of each species for 2 months in
heterospecific or conspecific pairs, partitioned by perforated galvanized iron
sheets, allowing exchange of chemical stimuli and ultrasonic vocalization. The
sexual attractiveness of male urine odor showed a tendency (marginal
significance) to increase in R. tanezumi caged with R. n. humiliatus, compared
with those in conspecific pairs. Hippocampal glucocorticoid receptor (GR) and
brain-derived nutrition factor (BDNF) mRNA were upregulated in R. n. humiliatus
and R. tanezumi, respectively, when the rats were caged in heterospecific pairs.
In Experiment 2, we kept juvenile male rats in individual cages in rooms with
either the same or the different species for 2 months, allowing chemical
interaction. The sexual attractiveness of male urine was significantly enhanced
in R. tanezumi, but reduced in R. n. humiliatus by heterospecific cues and mRNA
expression of hippocampal GR and BDNF were upregulated by heterospecific cues in
R. n. humiliatus and R. tanezumi, respectively. Although not identical, the
results from Experiments 1 and 2 were generally consistent. CONCLUSIONS: The
results of both experiments indicate that nonphysical/chronic interspecific
stimuli, particularly scent signals, between R. n. humiliatus and R. tanezumi may
negatively affect R. n. humiliatus and positively affect R. tanezumi. We infer
that chronic interspecific interactions may have contributed to the invasion of
R. tanezumi into the range of R. n. humiliatus in natural habitats.
PMID- 28413433
TI - Protoplast isolation prior to flow cytometry reveals clear patterns of
endoreduplication in potato tubers, related species, and some starchy root crops.
AB - BACKGROUND: Endoreduplication, the process of DNA replication in the absence of
cell division, is associated with specialized cellular function and increased
cell size. Genes controlling endoreduplication in tomato fruit have been shown to
affect mature fruit size. An efficient method of estimating endoreduplication is
required to study its role in plant organ development. Flow cytometry is often
utilized to evaluate endoreduplication, yet some tissues and species, among them
the tubers of Solanum tuberosum, remain intractable to routine tissue preparation
for flow cytometry. We aimed to develop a method through the use of protoplast
extraction preceding flow cytometry, specifically for the assessment of
endoreduplication in potato tubers. RESULTS: We present a method for appraising
endoreduplication in potato (Solanum tuberosum) tuber tissues. We evaluated this
method and observed consistent differences between pith and cortex of tubers and
between different cultivars, but no apparent relationship with whole tuber size.
Furthermore, we were able to observe distinct patterns of endoreduplication in 16
of 20 wild potato relatives, with mean endoreduplication index (EI) ranging from
0.94 to 2.62 endocycles per cell. The protocol was also applied to a panel of
starchy root crop species and, while only two of five yielded reliable flow
histograms, the two (sweet potato and turnip) exhibited substantially lower EIs
than wild and cultivated potato accessions. CONCLUSIONS: The protocol reported
herein has proven effective on tubers of a variety of potato cultivars and
related species, as well as storage roots of other starchy crops. This method
provides an important tool for the study of potato morphology and development
while revealing natural variation for endoreduplication which may have
agricultural relevance.
PMID- 28413434
TI - Multicolour localization microscopy by point-spread-function engineering.
AB - Super-resolution microscopy has revolutionized cellular imaging in recent years1
4. Methods relying on sequential localization of single point emitters enable
spatial tracking at ~10-40 nm resolution. Moreover, tracking and imaging in three
dimensions is made possible by various techniques, including point-spread
function (PSF) engineering5-9 -namely, encoding the axial (z) position of a point
source in the shape that it creates in the image plane. However, a remaining
challenge for localization-microscopy is efficient multicolour imaging - a task
of the utmost importance for contextualizing biological data. Normally,
multicolour imaging requires sequential imaging10, 11, multiple cameras12, or
segmented dedicated fields of view13, 14. Here, we demonstrate an alternate
strategy, the encoding of spectral information (colour), in addition to 3D
position, directly in the image. By exploiting chromatic dispersion, we design a
new class of optical phase masks that simultaneously yield controllably different
PSFs for different wavelengths, enabling simultaneous multicolour tracking or
super-resolution imaging in a single optical path.
PMID- 28413435
TI - Low prevalence of human mammary tumor virus (HMTV) in breast cancer patients from
Myanmar.
AB - BACKGROUND: Human mammary tumor virus (HMTV) is 90-95% homologous to mouse
mammary tumor virus (MMTV), one of the causal agents of murine mammary tumors.
HMTV (MMTV-like) sequences were reported to be present in human breast cancers
from several populations with a prevalence range of 0-78%; however, the
prevalence of HMTV in breast cancers from Myanmar remains unknown. METHODS: Fifty
eight breast cancer samples from Myanmar women were examined in this study. DNA
was isolated from formalin-fixed paraffin-embedded specimens, and HMTV envelope
sequences were detected by semi-nested PCR. The sequence of the PCR products was
also confirmed. RESULTS: Only 1.7% (1 of 58) of the breast cancers were positive
for HMTV, and the sequence of PCR products was 98.9% identical to the reference
HMTV sequence (GenBank accession No. AF243039). The tumor with HMTV was grade III
invasive ductal carcinoma, 7.0 cm in size with lymph node metastasis (T3, N1,
M0). CONCLUSIONS: We, for the first time, investigated the presence of HMTV in
Myanmar breast cancer patients. In accordance with other Asian studies, the
prevalence of HMTV in Myanmar was quite low, supporting the hypothesis that Asian
breast cancers have different etiologies than in Western countries, where HMTV is
more prevalent.
PMID- 28413436
TI - Predominance and association risk of Blastocystis hominis subtype I in colorectal
cancer: a case control study.
AB - BACKGROUND: Blastocystis, a genetically diverse intestinal parasite with
controversial pathogenic potential, has increasingly been incriminated for
diarrheal illness in immunocompromised individuals including colorectal cancer
(CRC) patients. The aim of the current study was to assess the possible
association between Blastocystis infection and CRC condition in Makkah, Saudi
Arabia (KSA). METHODS: Stool samples were collected from 80 non-cancer (NC) and
138 cancer subjects including 74 CRC patients and 64 patients with other cancers
outside gastrointestinal tract (COGT). Molecularly confirmed Blastocystis
isolates were genetically grouped and subtyped using multiplex polymerase chain
reaction with restriction fragment length polymorphism (PCR-RFLP) and sequence
tagged site primers-based PCR (PCR-STS), respectively. RESULTS: Blastocystis
hominis were confirmed in 29.7, 25 and 15% among CRC, COGT and NC patients,
respectively. Obtained Blastocystis isolates were initially categorized into 2
groups (A and C), which were subsequently subtyped into 3 different subtypes;
subtype-I (38%), subtype-II (44%) and subtype-V (22%). Interestingly, subtype-I
was the most predominantly detected subtype (54.5%) among CRC patients with a
significant association risk (COR 7.548; 95% CI: 1.629-34.987; P = 0.004).
CONCLUSION: To the best of our knowledge, the current study is the first to
provide genetic insights on the prevalence of Blastocystis hominis among CRC
patients in Makkah, KSA. Moreover, the study suggests for a possible association
between subtype-I of Blastocystis hominis and CRC, which could indicate a
potential influence of Blastocystis on CRC condition. Further studies are
required to confirm this association risk and to investigate the possible
underlying mechanism of postulated carcinogenic influence of Blastocystis hominis
subtype-I.
PMID- 28413437
TI - goSTAG: gene ontology subtrees to tag and annotate genes within a set.
AB - BACKGROUND: Over-representation analysis (ORA) detects enrichment of genes within
biological categories. Gene Ontology (GO) domains are commonly used for gene/gene
product annotation. When ORA is employed, often times there are hundreds of
statistically significant GO terms per gene set. Comparing enriched categories
between a large number of analyses and identifying the term within the GO
hierarchy with the most connections is challenging. Furthermore, ascertaining
biological themes representative of the samples can be highly subjective from the
interpretation of the enriched categories. RESULTS: We developed goSTAG for
utilizing GO Subtrees to Tag and Annotate Genes that are part of a set. Given
gene lists from microarray, RNA sequencing (RNA-Seq) or other genomic high
throughput technologies, goSTAG performs GO enrichment analysis and clusters the
GO terms based on the p-values from the significance tests. GO subtrees are
constructed for each cluster, and the term that has the most paths to the root
within the subtree is used to tag and annotate the cluster as the biological
theme. We tested goSTAG on a microarray gene expression data set of samples
acquired from the bone marrow of rats exposed to cancer therapeutic drugs to
determine whether the combination or the order of administration influenced bone
marrow toxicity at the level of gene expression. Several clusters were labeled
with GO biological processes (BPs) from the subtrees that are indicative of some
of the prominent pathways modulated in bone marrow from animals treated with an
oxaliplatin/topotecan combination. In particular, negative regulation of MAP
kinase activity was the biological theme exclusively in the cluster associated
with enrichment at 6 h after treatment with oxaliplatin followed by control.
However, nucleoside triphosphate catabolic process was the GO BP labeled
exclusively at 6 h after treatment with topotecan followed by control.
CONCLUSIONS: goSTAG converts gene lists from genomic analyses into biological
themes by enriching biological categories and constructing GO subtrees from over
represented terms in the clusters. The terms with the most paths to the root in
the subtree are used to represent the biological themes. goSTAG is developed in R
as a Bioconductor package and is available at
https://bioconductor.org/packages/goSTAG.
PMID- 28413438
TI - A case report of brief psychotic disorder with catalepsy associated with
sequential life-threatening events in a patient with advanced cancer.
AB - BACKGROUND: Cancer is commonly perceived as life-threatening and universally
stressful; however, brief psychotic disorder, which occurs in response to
extremely stressful events, has not been reported. CASE PRESENTATION: A 63-year
old woman, who was diagnosed as having pancreatic cancer with liver metastasis,
became unresponsive with very little reaction to verbal contact after sequential
life-threatening events, such as thrombosis of both pulmonary arteries and
stenosis of the third portion of the duodenum, due to disease progression over 3
weeks beginning with oncological emergency hospital admission. Laboratory
findings and electroencephalography were unremarkable. She maintained the
position when the psycho-oncologist raised her hand (catalepsy). She had no
medical history of psychiatric illness, or alcohol or drug abuse. From these
findings, she was suspected of having a brief psychotic disorder with catalepsy
and substupor, and 2.5 mg of haloperidol was administered. Her psychiatric
symptoms disappeared in 4 days and the diagnosis of brief psychotic disorder was
confirmed. CONCLUSIONS: Brief psychotic disorders can manifest in patients with
cancer. Careful clinical assessment is needed to correctly diagnose patients with
cancer who develop brief psychotic disorders and to identify those who will
benefit from correct treatment.
PMID- 28413439
TI - Family reintegration of homeless in Maputo and Matola: a descriptive study.
AB - BACKGROUND: Homelessness is a global and local social problem with underestimated
prevalence. It has been shown to increase the risk of mental illness, raising
concerns from mental health providers about the need for effective interventions
targeting this population. OBJECTIVES: The aim of this paper is to describe the
mental health status of the homeless people in two urban setting in a low-income
country, through using standardised clinical and socio-demographic assessments as
well assessing potential predictors of family integration versus non-family
integration among a group of homeless individuals receiving psychiatric and
psychosocial treatment. METHODS: A descriptive study was performed in Maputo and
Matola cities between 2008 and 2010. Homeless people with apparent mental illness
were mapped and recruited. The participants were referred from community to
hospital, using a multidisciplinary treatment model, according to their clinical
condition and later entered a family reintegration process. RESULTS: Seventy-one
homeless people were recruited (93.0% male; 80.3% unemployed). The most common
diagnosis was schizophrenia and other psychosis (46; 64.8%), followed by mental
and behaviour disorder related to substance misuse (21; 29.6%), and intellectual
disability (4; 5.6%). Family reintegration was achieved for 53.5% (38 patients).
Patients with intellectual disability were less reintegrated and those with
disorders related to substance use had better reinsertion in their families (Chi
square (2) = 6.1; p = 0.047). CONCLUSIONS: Family reintegration was achieved in
more than half of participants after hospitalization. Integration was higher in
cases of substance misuse, with those with associated intellectual disability
being more difficult to reintegrate. Trial registration Trial Registration
Number: NCT02936141, date of registration: 14/10/2016, retrospectively
registered.
PMID- 28413440
TI - Predictors of depression among patients receiving treatment for snakebite in
General Hospital, Kaltungo, Gombe State, Nigeria: August 2015.
AB - BACKGROUND: Snakebite though neglected, affects 5 million people yearly. More
neglected is the psychological effect of envenomation. We determined prevalence
and pattern of depression among patients admitted into snakebite wards of
Kaltungo General Hospital Nigeria, and percentage recognized by clinicians. We
also assessed for factors associated with depression. METHODS: In a descriptive
hospital based study, we used Patient Health questionnaire (PHQ-9) to make
diagnosis of depression among the patients. We reviewed patients' clinical
records to determine clinicians' recognition of depression. RESULTS: Of 187
interviews analyzed, 47 (25%) had depression with none recognized by attending
clinicians. Patients with snakebite complications (odd ratio [OR] 3.1, 95% CI 1.1
8.5), and previous history of snakebites (OR 2.7, 95% CI 1.1-6.1) were associated
with mild depression. Worrying about family welfare (OR 31.5, 95% CI 6.5-152.9),
financial loss (OR 14.6, 95% CI 1.8-121.5) and time loss (OR 14.6, 95% CI 1.8
121.5), past history of snakebites (OR 8.3, 95% CI 1.9-36.5) and lower income
(Mean difference -25,069 [84 USD], 95% CI 35,509 [118 USD]-14,630 [49 USD]) were
associated with severe depression. CONCLUSION: A quarter of in-patients of
snakebite wards of the general hospital had comorbid depression that went
unrecognized. Independent predictors of depression such as past history of
snakebite, worrying about relations and having snakebite complications could help
clinicians anticipate depression among patients. We recommend training of
clinicians in the hospital on recognition of common psychological disorders like
depression.
PMID- 28413441
TI - Prevalence and associated factors of attention deficit hyperactivity disorder
(ADHD) among Ugandan children; a cross-sectional study.
AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common
neuropsychiatric disorder among the children. The burden of ADHD or its
associated factors in Uganda are not known. The objective of this study was to
determine the prevalence and the associated factors of ADHD among children
attending the neurology and psychiatry clinics at Mulago National Referral
Hospital. METHODS: Using the disruptive behavior scale (45 items), we
investigated the presence of ADHD symptoms among children attending Mulago
Hospital. Questionnaires were administered to the primary care-takers of the
study participants to gather information on the factors associated with ADHD. All
children were subject to a clinical examination. Children presumed to have ADHD,
using the aforementioned rating scale were further assessed by a child
psychiatrist to confirm the diagnosis and associated co-morbid conditions.
RESULTS: The estimated prevalence of DSM-IV ADHD symptoms was 11%. Children aged
less than 10 years were four times likely to have ADHD (OR 4.1, 95% CI 1.7-9.6, p
< 0.001). The demographic factors independently associated with ADHD were age
less than 10 years, male gender, history of maternal abnormal vaginal discharge
during pregnancy, and no formal education or the highest level of education being
primary school. CONCLUSION: The prevalence of ADHD among children attending the
pediatric neurology and psychiatry clinics is high in our settings and is
associated with delayed milestones. Early identification and addressing the co
morbid conditions associated with ADHD such as epilepsy, autism spectrum of
disorder, conduct disorder, opposition defiant disorder and intellectual
disability in our setting is needed.
PMID- 28413442
TI - Specific coping strategies moderate the link between emotion expression deficits
and nonsuicidal self-injury in an inpatient sample of adolescents.
AB - BACKGROUND: Non-suicidal self-injury (NSSI) is a behavior of increasing
prevalence in adolescents with links to various negative mental health and
adjustment outcomes. Poor emotion expression has been linked with NSSI use,
whereas the use of adaptive coping strategies has been identified as a protective
factor against NSSI. The current study examined whether specific coping
strategies moderate the relation between poor emotion expression and NSSI, and
whether moderation is conditional on adolescent gender. METHODS: Ninety-five
adolescents hospitalized on an acute care inpatient psychiatric unit completed
questionnaires measuring NSSI, emotion expression and use of specific coping
strategies (i.e., problem-focused coping, positive reframing coping, support
seeking, avoidance, and distraction). RESULTS: Results indicated that poor
emotion expression was positively associated with NSSI. Positive reframing and
support seeking emerged as significant moderators of the poor emotion expression
NSSI link. This result was not conditional upon adolescent gender. Problem
focused coping, avoidance, and distraction did not emerge as significant
moderators. CONCLUSIONS: Encouraging youth to use particular coping strategies
might protect against the negative impact of emotion expression deficits for both
boys and girls.
PMID- 28413443
TI - Molecular and biochemical characterization of recombinant cel12B, cel8C, and
peh28 overexpressed in Escherichia coli and their potential in biofuel
production.
AB - BACKGROUND: The high crystallinity of cellulosic biomass myofibrils as well as
the complexity of their intermolecular structure is a significant impediment for
biofuel production. Cloning of celB-, celC-encoded cellulases (cel12B and cel8C)
and peh-encoded polygalacturonase (peh28) from Pectobacterium carotovorum subsp.
carotovorum (Pcc) was carried out in our previous study using Escherichia coli as
a host vector. The current study partially characterizes the enzymes' molecular
structures as well as their catalytic performance on different substrates which
can be used to improve their potential for lignocellulosic biomass conversion.
RESULTS: beta-Jelly roll topology, (alpha/alpha)6 antiparallel helices and right
handed beta-helices were the folds identified for cel12B, cel8C, and peh28,
respectively, in their corresponding protein model structures. Purifications of
17.4-, 6.2-, and 6.0-fold, compared to crude extract, were achieved for cel12B
and cel8C, and peh28, respectively, using specific membrane ultrafiltrations and
size-exclusion chromatography. Avicel and carboxymethyl cellulose (CMC) were
substrates for cel12B, whereas for cel8C catalytic activity was only shown on
CMC. The enzymes displayed significant synergy on CMC but not on Avicel when
tested for 3 h at 45 degrees C. No observed beta-glucosidase activities were
identified for cel8C and cel12B when tested on p-nitrophenyl-beta-d
glucopyranoside. Activity stimulation of 130% was observed when a recombinant
beta-glucosidase from Pcc was added to cel8C and cel12B as tested for 3 h at 45
degrees C. Optimum temperature and pH of 45 degrees C and 5.4, respectively,
were identified for all three enzymes using various substrates. Catalytic
efficiencies (kcat/Km) were calculated for cel12B and cel8C on CMC as 0.141 and
2.45 ml/mg/s respectively, at 45 degrees C and pH 5.0 and for peh28 on
polygalacturonic acid as 4.87 ml/mg/s, at 40 degrees C and pH 5.0. Glucose and
cellobiose were the end-products identified for cel8C, cel12B, and beta
glucosidase acting together on Avicel or CMC, while galacturonic acid and other
minor co-products were identified for peh28 action on pectin. CONCLUSIONS: This
study provides some insight into which parameters should be optimized when
application of cel8C, cel12B, and peh28 to biomass conversion is the goal.
PMID- 28413444
TI - Functional photosystem I maintains proper energy balance during nitrogen
depletion in Chlamydomonas reinhardtii, promoting triacylglycerol accumulation.
AB - BACKGROUND: Nutrient deprivation causes significant stress to the unicellular
microalga, Chlamydomonas reinhardtii, which responds by significantly altering
its metabolic program. Following N deprivation, the accumulation of starch and
triacylglycerols (TAGs) is significantly altered following massive reprogramming
of cellular metabolism. One protein that was found to change dramatically and
early to this stress was TAB2, a photosystem I (PSI) translation initiation
factor, whose transcript and protein levels increased significantly after only 30
min of N deprivation. A detailed physiological and omics-based analysis of an
insertional mutant of Chlamydomonas with reduced TAB2 function was conducted to
determine what role the functional PSI plays in regulating the cellular response
to N deprivation. RESULTS: The tab2 mutant displayed increased acetate
assimilation and elevated starch levels during the first 6 h of N deprivation,
followed by a shift toward altered amino acid synthesis, reduced TAG content and
altered fatty acid profiles. These results suggested a central role for PSI in
controlling cellular metabolism and its implication in regulation of lipid/starch
partitioning. Time course analyses of the tab2 mutant versus wild type under N
deprived versus N replete conditions revealed changes in the ATP/NADPH ratio and
suggested that TAG biosynthesis may be associated with maintaining the redox
state of the cell during N deprivation. The loss of ability to accumulate TAG in
the tab2 mutant co-occurred with an up-regulation of photo-protective mechanisms,
suggesting that the synthesis of TAG in the wild type occurs not only as a
temporal energy sink, but also as a protective electron sink. CONCLUSIONS: By
exploiting the tab2 mutation in the cells of C. reinhardtii cultured under
autotrophic, mixotrophic, and heterotrophic conditions during nitrogen replete
growth and for the first 8 days of nitrogen deprivation, we showed that TAG
accumulation and lipid/starch partitioning are dynamically regulated by
alterations in PSI function, which concomitantly alters the immediate ATP/NADPH
demand. This occurs even without removal of nitrogen from the medium, but
sufficient external carbon must nevertheless be available. Efforts to increase
lipid accumulation in algae such as Chlamydomonas need to consider carefully how
the energy balance of the cell is involved in or affected by such efforts and
that numerous layers of metabolic and genetic regulatory control are likely to
interfere with such efforts to control oil biosynthesis. Such knowledge will
enable synthetic biology approaches to alter the response to the N depletion
stress, leading to rewiring of the regulatory networks so that lipid accumulation
could be turned on in the absence of N deprivation, allowing for the development
of algal production strains with highly enhanced lipid accumulation profiles.
PMID- 28413446
TI - Artificial miRNA inhibition of phosphoenolpyruvate carboxylase increases fatty
acid production in a green microalga Chlamydomonas reinhardtii.
AB - BACKGROUND: Nutrient limitation, such as nitrogen depletion, is the most widely
used method for improving microalgae fatty acid production; however, these harsh
conditions also inhibit algal growth significantly and even kill cells at all. To
avoid these problems, we used artificial microRNA (amiRNA) technology as a useful
tool to manipulate metabolic pathways to increase fatty acid contents effectively
in the green microalga Chlamydomonas reinhardtii. We down-regulated the
expression of phosphoenolpyruvate carboxylase (PEPC), which catalyzes the
formation of oxaloacetate from phosphoenolpyruvate and regulates carbon flux.
RESULTS: amiRNAs against two CrPEPC genes were designed and transformed into
Chlamydomonas cells and amiRNAs were induced by heat shock treatment. The
transcription levels of amiRNAs increased 16-28 times, resulting in the
remarkable decreases of the expression of CrPEPCs. In the end, inhibiting the
expression of the CrPEPC genes dramatically increased the total fatty acid
content in the transgenic algae by 28.7-48.6%, which mostly increased the content
of C16-C22 fatty acids. Furthermore, the highest content was that of C18:3n3 with
an average increase of 35.75%, while C20-C22 fatty acid content significantly
increased by 85-160%. CONCLUSIONS: Overall our results suggest that heat shock
treatment induced the expression of amiRNAs, which can effectively down-regulate
the expression of CrPEPCs in C. reinhardtii, resulting in an increase of fatty
acid synthesis with the most significant increase occurring for C16 to C22 fatty
acids.
PMID- 28413445
TI - Valorization of untreated rice bran towards bioflocculant using a lignocellulose
degrading strain and its use in microalgal biomass harvest.
AB - BACKGROUND: Microalgae are currently considered as a promising feedstock for the
production of biofuels and high-value products. However, the efficient harvest of
microalgal biomasses from their culture broth is a major challenge. The
harvesting of algal biomass by flocculation combined with gravity sedimentation
is more convenient and cost-effective than traditional methods such as
centrifugation and filtration. Compared to inorganic and chemically synthetic
flocculants, bioflocculants are a suitable choice for microalgal harvest due to
their biodegradable and nontoxic properties. Nonetheless, the high production
costs associated with expensive substrates hinder the commercial applications of
bioflocculants. Previous studies have shown that the hydrolysates of
lignocellulosic biomasses from dilute acid hydrolysis can be utilized as an
inexpensive carbon source for the production of bioflocculants. However, the
toxic by-products generated in the dilute acid hydrolysis step limit the
efficiency of subsequent fermentation. The strains that produce bioflocculants by
using untreated lignocellulosic materials can circumvent the pretreatment
process, as well as promote the application of bioflocculants in microalgal
harvest. RESULTS: Under alkaline fermentation conditions, the alkaliphilic strain
Bacillus agaradhaerens C9 secreted 1.69 IU/mL of alkali-tolerant xylanase and
0.06 IU/mL of cellulase, indicating that this particular strain can efficiently
convert untreated rice bran into bioflocculant (RBBF-C9), thereby circumventing
rice bran pretreatment for downstream fermentation. The optimal fermentation
conditions that result in the highest bioflocculant yield (12.94 g/L) were as
follows: 20 g/L of untreated rice bran, 3 g/L of yeast extract, and 20 g/L of
Na2CO3 at 37 degrees C for 24 h. RBBF-C9 contained 74.12% polysaccharides and
4.51% proteins, and was estimated to be 137 kDa. Furthermore, the bioflocculant
RBBF-C9 exhibited good flocculating efficiency (91.05%) of oil alga Chlorella
minutissima UTEX2341 when 60 mg/L of RBBF-C9 was added into the algal culture
broth. CONCLUSIONS: This study demonstrated that untreated rice bran is a
suitable inexpensive substrate for the production of bioflocculants, and thus
provides a novel approach in utilizing rice bran. The extracted bioflocculants
may be potentially used in biomass harvesting of the oil algae C. minutissima
UTEX2341 from the culture broth.
PMID- 28413447
TI - Enhancement of ethanol production from green liquor-ethanol-pretreated sugarcane
bagasse by glucose-xylose cofermentation at high solid loadings with mixed
Saccharomyces cerevisiae strains.
AB - BACKGROUND: Efficient cofermentation of glucose and xylose is necessary for
economically feasible bioethanol production from lignocellulosic biomass. Here,
we demonstrate pretreatment of sugarcane bagasse (SCB) with green liquor (GL)
combined with ethanol (GL-Ethanol) by adding different GL amounts. The common
Saccharomyces cerevisiae (CSC) and thermophilic S. cerevisiae (TSC) strains were
used and different yeast cell mass ratios (CSC to TSC) were compared. The
simultaneous saccharification and cofermentation (SSF/SSCF) process was performed
by 5-20% (w/v) dry substrate (DS) solid loadings to determine optimal conditions
for the co-consumption of glucose and xylose. RESULTS: Compared to previous
studies that tested fermentation of glucose using only the CSC, we obtained
higher ethanol yield and concentration (92.80% and 23.22 g/L) with 1.5 mL GL/g-DS
GL-Ethanol-pretreated SCB at 5% (w/v) solid loading and a CSC-to-TSC yeast cell
mass ratio of 1:2 (w/w). Using 10% (w/v) solid loading under the same conditions,
the ethanol concentration increased to 42.53 g/L but the ethanol yield decreased
to 84.99%. In addition, an increase in the solid loading up to a certain point
led to an increase in the ethanol concentration from 1.5 mL GL/g-DS-pretreated
SCB. The highest ethanol concentration (68.24 g/L) was obtained with 15% (w/v)
solid loading, using a CSC-to-TSC yeast cell mass ratio of 1:3 (w/w).
CONCLUSIONS: GL-Ethanol pretreatment is a promising pretreatment method for
improving both glucan and xylan conversion efficiencies of SCB. There was a
competitive relationship between the two yeast strains, and the glucose and
xylose utilization ability of the TSC was better than that of the CSC. Ethanol
concentration was obviously increased at high solid loading, but the yield
decreased as a result of an increase in the viscosity and inhibitor levels in the
fermentation system. Finally, the SSCF of GL-Ethanol-pretreated SCB with mixed S.
cerevisiae strains increased ethanol concentration and was an effective
conversion process for ethanol production at high solid loading.
PMID- 28413448
TI - Genetic and epigenetic characterization of the tumors in a patient with a tongue
primary tumor, a recurrence and a pharyngoesophageal second primary tumor.
AB - BACKGROUND: The choice of therapeutic modality for oral carcinoma in recurrent or
second primary tumors remains controversial, as the treatment modalities
available might be reduced by the treatment of the first tumor, and the overall
survival is lower when compared with patients with a single or first tumor.
Identifying biomarkers that predict the risk of relapse and the response to
treatment is an emerging clinical issue. CASE PRESENTATION: A Caucasian 49-years
old man was treated with chemotherapy followed by chemoradiotherapy for a primary
left side tongue tumor, achieving a complete response. After 49-months of follow
up, a local recurrence was diagnosed. After 3 months, a second primary tumor at
the pharyngoesophageal region was detected. Genomic and epigenetic
characterization of these three tumors was performed using array Comparative
Genomic Hybridization, Multiplex Ligation-dependent Probe Amplification (MLPA)
and Methylation Specific MLPA. RESULTS: The three tumors of this patient shared
several imbalances in all chromosomes excluding chromosomes 9, 20 and 22, where
genes related to important functional mechanisms of tumorigenesis are mapped. The
shared genomic imbalances, such as losses at 1p, 2p, 3p, 4q, 5q, 6q, 7q, 8p, 10p,
11q, 12p, 12q, 13q, 15q, 16p, 16q, 17p, 17q, 18q, 19p, 19q, 21q and Xp and gains
at 3q, 7q, 14q and 15q showed a common clonal origin for the diagnosed relapses.
We identified some chromosomal imbalances and genes mapped in the chromosomes 2,
3, 4, 6, 7, 11, 14, 17, 18 and 22 as putative linked to chemoradioresistance and
chemoradiosensitivity. We also observed that gains in short arm of chromosomes 6,
7, 8 and 18 were acquired after treatment of the primary tumor. We identified
losses of VHL gene and promoter methylation of WT1 and GATA5 genes, as predictors
of relapses. CONCLUSIONS: A common clonal origin for the diagnosed relapses was
observed and we identified some putative candidate biomarkers of prognosis,
relapse risk and treatment response that could guide the development of
management strategies for these patients.
PMID- 28413449
TI - Links between DNA methylation and nucleosome occupancy in the human genome.
AB - BACKGROUND: DNA methylation is an epigenetic modification that is enriched in
heterochromatin but depleted at active promoters and enhancers. However, the
debate on whether or not DNA methylation is a reliable indicator of high
nucleosome occupancy has not been settled. For example, the methylation levels of
DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while
other studies have shown that the nucleosome core is the preferred site of
methylation. In this study, we make progress toward understanding these
conflicting phenomena by implementing a bioinformatics approach that combines
MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and
nucleosome occupancy throughout the human genome. RESULTS: The results
demonstrated that increasing methylated CpG density is correlated with nucleosome
occupancy in the total genome and within nearly all subgenomic regions. Features
with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36
trimethylated peaks, and methylated CpG islands are among the highest nucleosome
occupied elements in the genome, while some of the lowest occupancies are
displayed by unmethylated CpG islands and unmethylated transcription factor
binding sites. Additionally, outside of CpG islands, the density of CpGs within
nucleosomes was shown to be important for the nucleosomal location of DNA
methylation with low CpG frequencies favoring linker methylation and high CpG
frequencies favoring core particle methylation. Prominent exceptions to the
correlations between methylated CpG density and nucleosome occupancy include CpG
islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and
these modifications, along with DNA methylation, distinguish the major silencing
mechanisms of the human epigenome. CONCLUSIONS: Thus, the relationship between
DNA methylation and nucleosome occupancy is influenced by the density of
methylated CpG dinucleotides and by other epigenomic components in chromatin.
PMID- 28413450
TI - Fetal testis organ culture reproduces the dynamics of epigenetic reprogramming in
rat gonocytes.
AB - BACKGROUND: Epigenetic reprogramming is a critical step in male germ cell
development that occurs during perinatal life. It is characterized by the
remodeling of different epigenetic marks such as DNA methylation (5mC) and
methylation of histone H3. It has been suggested that endocrine disruptors can
affect the male germline epigenome by altering epigenetic reprogramming, but the
mechanisms involved are still unknown. We have previously used an organ culture
system that maintains the development of the different fetal testis cell types,
to evaluate the effects of various endocrine disruptors on gametogenesis and
steroidogenesis in the rat. We hypothesize that this culture model can reproduce
the epigenetic reprogramming in gonocytes. Our aim was to establish the kinetics
of three epigenetic marks throughout perinatal development in rats in vivo and
compare them after different culture times. RESULTS: Using immunofluorescence, we
showed that H3K4me2 transiently increased in gonocytes at 18.5 days post-coitum
(dpc), while H3K4me3 displayed a stable increase in gonocytes from 18.5 dpc until
after birth. 5mC progressively increased from 20.5 dpc until after birth. Using
GFP-positive gonocytes purified from GCS-EGFP rats, we established the chronology
of re-methylation of H19 and Snrpn in rat gonocytes. Most importantly, using
testis explanted at 16.5 or 18.5 dpc and cultured for 2-4 days, we demonstrated
that the kinetics of changes in H3K4me2, H3K4me3, global DNA methylation and on
parental imprints can generally be reproduced ex vivo with the model of organ
culture without the addition of serum. CONCLUSIONS: This study reveals the
chronology of three epigenetic marks (H3K4me2, H3K4me3 and 5mC) and the patterns
of methylation of H19 and Snrpn differentially methylated regions in rat
gonocytes during perinatal development. Most importantly, our results suggest
that the organ culture can reproduce the process of epigenetic reprogramming and
can be used to study the impact of environmental chemicals on the establishment
of the male germ cell epigenome.
PMID- 28413451
TI - Differential DNA methylation at conserved non-genic elements and evidence for
transgenerational inheritance following developmental exposure to mono(2
ethylhexyl) phthalate and 5-azacytidine in zebrafish.
AB - BACKGROUND: Exposure to environmental stressors during development may lead to
latent and transgenerational adverse health effects. To understand the role of
DNA methylation in these effects, we used zebrafish as a vertebrate model to
investigate heritable changes in DNA methylation following chemical-induced
stress during early development. We exposed zebrafish embryos to non-embryotoxic
concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl)
phthalate (MEHP, 30 uM) and the DNA methyltransferase 1 inhibitor 5-azacytidine
(5AC, 10 uM). Direct, latent and transgenerational effects on DNA methylation
were assessed using global, genome-wide and locus-specific DNA methylation
analyses. RESULTS: Following direct exposure in zebrafish embryos from 0 to 6
days post-fertilization, genome-wide analysis revealed a multitude of
differentially methylated regions, strongly enriched at conserved non-genic
elements for both compounds. Pathways involved in adipogenesis were enriched with
the putative obesogenic compound MEHP. Exposure to 5AC resulted in enrichment of
pathways involved in embryonic development and transgenerational effects on
larval body length. Locus-specific methylation analysis of 10 differentially
methylated sites revealed six of these loci differentially methylated in sperm
sampled from adult zebrafish exposed during development to 5AC, and in first and
second generation larvae. With MEHP, consistent changes were found at 2 specific
loci in first and second generation larvae. CONCLUSIONS: Our results suggest a
functional role for DNA methylation on cis-regulatory conserved elements
following developmental exposure to compounds. Effects on these regions are
potentially transferred to subsequent generations.
PMID- 28413452
TI - Ankle and toe muscle strength characteristics in runners with a history of medial
tibial stress syndrome.
AB - BACKGROUND: A high proportion of flexor digitorum longus attachment is found at
the posteromedial border of the tibia, which is the most common location of
medial tibial stress syndrome (MTSS). Therefore, plantar flexion strength of the
lesser toes could be related to MTSS; however, the relationship between MTSS and
muscle strength of the hallux and lesser toes is not yet evaluated due to the
lack of quantitative methods. This study investigated the muscle strength
characteristics in runners with a history of MTSS by using a newly developed
device to measure the muscle strength of the hallux, lesser toes, and ankle.
METHODS: This study comprised 27 collegiate male runner participants (20.0 +/-
1.6 years, 172.1 +/- 5.1 cm, 57.5 +/- 4.0 kg). Maximal voluntary isometric
contraction (MVIC) torque of the plantar flexion, dorsiflexion, inversion, and
eversion of the ankle were measured by using an electric dynamometer. MVIC torque
of the 1st metatarsophalangeal joint (MTPJ) and 2nd-5th MTPJ were measured by
using a custom-made torque-measuring device. MVIC torques were compared between
runners with and without a history of MTSS. RESULTS: MVIC torque of the 1st MTPJ
plantar flexion was significantly higher in runners with a history of MTSS than
in those without it. In contrast, there were no significant differences in the
MVIC torque values of the 2nd-5th MTPJ plantar flexion and each MVIC torque of
the ankle between runners with and without a history of MTSS. CONCLUSION: A
history of MTSS increased the isometric FHL strength.
PMID- 28413453
TI - Amelioration of intestinal and systemic sequelae of murine Campylobacter jejuni
infection by probiotic VSL#3 treatment.
AB - BACKGROUND: The incidence of human Campylobacter jejuni infections is
progressively increasing worldwide. Probiotic compounds might open up valuable
tools to decrease pathogen burden and subsequent pro-inflammatory immune
responses, but in vivo data are scarce. METHODS AND RESULTS: Secondary abiotic
mice generated by broad-spectrum antibiotic treatment were perorally challenged
with the commercial probiotic compound VSL#3 consisting of Streptococcus
thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium
infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus
paracasei, and Lactobacillus delbrueckii ssp. bulgaricus) either 5 days before
(i.e. prophylactic regimen) or after (i.e. therapeutic regimen) peroral C. jejuni
strain 81-176 infection, and analyzed 3 weeks following the initial bacterial re
association. Upon challenge, mice were colonized with the probiotic bacteria
and/or C. jejuni at comparable intestinal loads, but co-colonization did not
result in reduction of the pathogen burden. Remarkably, prophylactic as well as
therapeutic VSL#3 treatment of C. jejuni infected mice ameliorated intestinal
apoptosis and pro-inflammatory immune responses as indicated by lower numbers of
innate and adaptive immune cell populations in the murine colon upon probiotic
prophylaxis or treatment and reduced colonic concentrations of pro-inflammatory
mediators including IL-6 and MCP-1. Importantly, concentrations of anti
inflammatory mediators such as IL-10 were significantly elevated in the colon of
probiotics treated mice as compared to untreated controls. Strikingly,
prophylactic VSL#3 treatment attenuated C. jejuni induced systemic pro
inflammatory responses as indicated by less TNF and IL-12p70 secretion in the
spleen of VSL#3 pre-treated as compared to non-treated mice. CONCLUSION:
Administration of probiotic formulations such as VSL#3 might open up valuable
strategies for prophylaxis and/or treatment of C. jejuni induced intestinal and
systemic sequelae in vivo by the suppression of pro-inflammatory and induction of
anti-inflammatory responses.
PMID- 28413455
TI - Letter to editor: The waist circumference-adjusted associations between
hyperuricemia and other lifestyle-related diseases: methodological issues in
cross-sectional study.
PMID- 28413454
TI - Helicobacter pylori vacA s1m1 genotype but not cagA or babA2 increase the risk of
ulcer and gastric cancer in patients from Southern Mexico.
AB - BACKGROUND: The vacA, cagA and babA2 genotypes of Helicobacter pylori are
associated with gastric pathology. The objectives were to determine the frequency
of infection and distribution of the vacA, cagA and babA2 genotypes of H. pylori
in patients with gastric ulcer, chronic gastritis and gastric cancer, and to
evaluate the association of virulent genotypes with diagnosis. METHODS: We
studied 921 patients with symptoms of dyspepsia or with presumptive diagnosis of
gastric cancer. The DNA of H. pylori and the vacA, cagA and babA2 genes was
detected by PCR in total DNA from gastric biopsies. The association of H. pylori
and of its cagA, vacA and babA2 genotypes with diagnosis was determined by
calculating the odds ratio (OR). RESULTS: Chronic gastritis was confirmed in 767
patients, gastric ulcer in 115 and cancer in 39. The prevalence of H. pylori was
47.8, 49.6 and 61.5% in those groups, respectively. H. pylori was more frequent
in the surrounding tissue (69.2%) than in the tumor (53.8%). The vacA s1m1
genotype predominated in the three groups (45.2, 61.4 and 83.3%, respectively).
H. pylori was associated with cancer (ORadjusted = 2.08; 95% CI 1.05-4.13; p =
0.035) but not with ulcer (ORadjusted = 1.07; 95% CI 0.71-1.61; p = 0.728). The
s1m1 genotype was associated with ulcer and cancer (ORadjusted = 2.02; 95% CI
1.12-3.62; p = 0.019 and ORadjusted = 6.58; 95% CI 2.15-20.08; p = 0.001,
respectively). babA2 was associated with gastric cancer, and cagA was not
associated with the diagnosis. CONCLUSIONS: In population from Southern Mexico,
H. pylori and the s1m1 genotype were associated with gastric cancer and the
s1m1/cagA+/babA2+ strains predominated in tumor and adjacent tissue.
PMID- 28413456
TI - Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel
syndrome.
AB - Irritable bowel syndrome (IBS) is a functional bowel disease with a complicated
etiopathogenesis, often characterized by gastrointestinal motility disorder and
high visceral sensitivity. IBS is a comprehensive multi-systemic disorder, with
the interaction of multiple factors, such as mental stress, intestinal function
and flora, heredity, resulting in the disease. The existence of a common
mechanism underlying the aforementioned factors is currently unknown. The lack of
therapies that comprehensively address the disease symptoms, including abdominal
pain and diarrhea, is a limitation of current IBS management. The current review
has explored the role of the SCF/c-Kit receptor/ligand system in IBS. The SCF/c
Kit system constitutes a classical ligand/receptor tyrosine kinase signaling
system that mediates inflammation and smooth muscle contraction. Additionally, it
provides trophic support to neural crest-derived cell types, including the
enteric nervous system and mast cells. The regulation of SCF/c-Kit on the
interstitial cells of Cajal (ICC) suggest that it may play a key role in the
aberrant intestinal dynamics and high visceral sensitivity observed in IBS. The
role of the SCF/c-Kit system in intestinal motility, inflammation and nerve
growth has been reported. From the available biomedical evidence on the
pathogenesis of IBS, it has been concluded that the SCF-c-Kit system is a
potential therapeutic target for rational drug design in the treatment of IBS.
PMID- 28413457
TI - Persicarin isolated from Oenanthe javanica protects against diabetes-induced
oxidative stress and inflammation in the liver of streptozotocin-induced type 1
diabetic mice.
AB - Persicarin is one of the major components of the Oenanthe javanica (water
dropwort). The present study was aimed to evaluate the role of persicarin in the
hepatic tissue of streptozotocin-induced type 1 diabetic mice. Diabetes was
induced by single intra-peritoneal injection of streptozotocin (120 mg/kg body
weight) and then oral administration of persicarin at a dose 2.5 and 5 mg/kg body
weight for 10 days. Serum and hepatic glucose levels were increased in diabetic
control mice, while persicarin treatment groups were markedly reduced. Also, the
increased levels of ALT and AST in serum were improved by persicarin. In our
results revealed that persicarin suppressed increased oxidative stress parameter
(reactive oxygen species, peroxinitrite, and thiobarbituric acid-reactive
substance), nicotinamide adenine dinucleotide phosphate oxidase subunit (Nox-4
and P47phox) and inflammatory related makers (NF-kappaB, AP-1, TGF-beta, COX-2,
and iNOS). These results suggest that persicarin protects against liver damage by
attenuating oxidative stress and inflammatory response under hyperglycemic
conditions. Thus, persicarin could perform as a potential therapeutic agent for
the treatment of diabetic mellitus.
PMID- 28413458
TI - miR-9 functions as a tumor inhibitor of cell proliferation in epithelial ovarian
cancer through targeting the SDF-1/CXCR4 pathway.
AB - The current study aimed to investigate the potential role of miR-9 in the
inhibition of ovarian cancer progression through the stromal cell-derived factor
1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) pathway and to provide a
theoretical basis for the diagnosis and treatment of ovarian cancer. Human
ovarian cancer OVCAR-3 cells were transfected with miR-9 short hairpin RNA
(shRNA). The effect of miR-9 on the mRNA expression levels of CXCR4 were analyzed
using reverse transcription-quantitative polymerase chain reaction. The effects
of miR-9 on OVCAR-3 cell proliferation, invasion and apoptotic ability were
detected using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide
assay, Matrigel method, and Annexin V-fluorescein isothiocyanate flow cytometry,
respectively. In addition, expression levels of SDF-1/CXCR4 pathway associated
proteins were determined by western blot analysis. mRNA expression levels of
CXCR4 in OVCAR-3 cells transfected with miR-9 shRNA was significantly
downregulated compared with the blank and control groups (P<0.05). Furthermore,
compared with the two control groups, the current results revealed that miR-9
inhibited cell proliferation, suppressed invasive ability and induced cell
apoptosis in OVCAR-3 cells (P<0.05). Finally, it was observed that miR-9
functioned as a tumor inhibitor through the SDF-1/CXCR4 pathway by suppressing
the expression levels of extracellular signal-regulated kinase 1 (ERK1), ERK2 and
matrix metalloproteinase-9 proteins. The present study suggested that miR-9 may
function as a promising tumor inhibitor for ovarian cancer through targeting the
SDF-1/CXCR4 pathway.
PMID- 28413459
TI - Expression levels of TGF-beta1 and CTGF are associated with the severity of
Duchenne muscular dystrophy.
AB - The present study aimed to analyze the association of transforming growth factor
beta1 (TGF-beta1) and connective tissue growth factor (CTGF) expression levels in
skeletal muscle with the clinical manifestation of Duchenne muscular dystrophy
(DMD). A total of 18 cases of DMD, which were confirmed by routine pathological
diagnosis were recruited into the present study, along with 8 subjects who
suffered from acute trauma but did not present any neuromuscular diseases and
were enrolled as the healthy controls. Immunohistochemical staining was used to
detect the expression levels of CTGF and TGF-beta1 in muscle biopsy specimens.
Furthermore, Spearman rank correlation analysis was conducted among the
expression levels of CTGF and TGF-beta1, age, clinical severity and pathological
severity in DMD patients. The immunohistochemical staining results revealed that
the expression levels of CTGF and TGF-beta1 were significantly increased in the
DMD group compared with those in the control group (P<0.05). These levels were
not found to be significantly correlated with the onset age (P>0.05), but there
was a significant correlation with the degree of pathology and clinical severity
(P<0.05). In conclusion, an upregulated expression of CTGF and TGF-beta1 was
revealed in the skeletal muscle of DMD patients, which were in positive
correlation with the degree of pathology and clinical severity. These two factors
may be involved in the pathophysiology of fibrosis in DMD.
PMID- 28413460
TI - Early application of low-dose glucocorticoid improves acute respiratory distress
syndrome: A meta-analysis of randomized controlled trials.
AB - Previous clinical trials have investigated the effect of glucocorticoid therapy
in acute respiratory distress syndrome (ARDS), with controversial results,
particularly with regard to the early administration of low dose glucocorticoid.
The present meta-analysis aimed to assess whether the application of
glucocorticoid was able to reduce mortality in patients with ARDS. A literature
search was performed using online databases, including MEDLINE, Embase, Cochrane
and CNKI regardless of whether the studies were published in English or Chinese.
Following assessment via inclusion and exclusion criteria, two reviewers screened
controlled randomized trials which investigated glucocorticoid therapy in ARDS
patients and independently extracted data. The quality of all of the included
trials was evaluated based on blinding, randomization and other methods. A total
of 14 studies with 1,441 patients met the inclusion criteria. The results of the
meta-analysis demonstrated that glucocorticoid significantly reduced the overall
mortality of patients with ARDS [relative ratio (RR), 0.68; 95% confidence
interval (CI), 0.50-0.91; P<0.05], particularly with a low-dose of glucocorticoid
(RR, 0.57; 95% CI, 0.39-0.84; P<0.05) at the early phase of ARDS (RR, 0.37; 95%
CI, 0.16-0.86; P<0.05), and a longer duration of steroids (RR, 0.44; 95% CI, 0.30
0.64; P<0.05). Administration of steroids also significantly increased the number
of days that patients remained alive and were off mechanical ventilation (RR,
3.08; 95% CI, 1.49-4.68; P<0.05) without significantly increasing the novel
infection rate (RR, 1.00; 95% CI, 0.44-2.25; P<0.05). Due to inconsistencies and
other limitations, the quality of the studies used for the meta-analysis of the
effect of glucocorticoid on mortality was low. In conclusion, early use of low
dose glucocorticoid may effectively reduce mortality in patients with ARDS.
However, this conclusion may be affected by the limited quality of the studies
included in the present meta-analysis.
PMID- 28413461
TI - Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose
deprivation and reoxygenation in human brain microvascular endothelial cells.
AB - Cerebral ischemia/reperfusion (I/R) injury leads to brain vascular dysfunction,
which is characterized by endothelial cell injury or death. Long noncoding (lnc)
RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reportedly
associated with endothelial cell functions and dysfunctions. In the present
study, the role of MALAT1 in I/R-induced cerebral vascular endothelial cell
apoptosis was explored using oxygen-glucose deprivation and reoxygenation (OGD-R)
as an in vitro I/R injury model. Primary human brain microvascular endothelial
cells were cultured under OGD-R, and the expression levels of MALAT1 and cell
apoptosis were measured at 6, 9, 12, 24 and 36 h post-reoxygenation. The
expression levels of MALAT1 and the apoptotic rate of cells exposed to OGD-R
exhibited contrasting trends following reoxygenation. Following OGD-R, lentiviral
overexpression of MALAT1 increased phosphatidylinositol 3-kinase (PI3K)
activities and the activation of Akt phosphorylation, and decreased cell
apoptosis and caspase 3 activities, which were successfully abolished by
treatment with a PI3K inhibitor, Wortmannin. Conversely, lentiviral knockdown of
MALAT1 decreased PI3K activities and the activation of Akt phosphorylation, and
increased cell apoptosis and caspase 3 activity. Overexpression and knockdown of
MALAT1 exhibited no significant effects on OGD-R-induced reactive oxygen species
(ROS) production. In conclusion, to the best of our knowledge, the present study
was the first to suggest that lncRNA MALAT1 may protect human brain vascular
endothelial cells from OGD-R-induced apoptosis via a PI3K-dependent mechanism.
These findings suggest that MALAT1 may be a potential novel therapeutic target
for cerebral I/R injury.
PMID- 28413462
TI - Identification of miRNA biomarkers of pneumonia using RNA-sequencing and
bioinformatics analysis.
AB - Pneumonia is a lower respiratory tract infection that causes dramatic mortality
worldwide. The present study aimed to investigate the pathogenesis of pneumonia
and identify microRNA (miRNA) biomarkers as candidates for targeted therapy. RNA
from the peripheral blood plasma of participants with pneumonia (severe, n=9; non
severe, n=9) and controls (n=9) was isolated and paired-end sequencing was
performed on an Illumina HiSeq4000 system. Following the processing of raw reads,
the sequences were aligned against the Genome Reference Consortium human genome
assembly 38 reference genome using Bowtie2 software. Reads per kilobase of
transcript per million mapped read values were obtained and the limma software
package was used to identify differentially expressed miRNAs (DE-miRs). Then, DE
miR targets were predicted and subjected to enrichment analysis. In addition, a
protein-protein interaction (PPI) network of the predicted targets was
constructed. This analysis identified 11 key DE-miRs in pneumonia samples,
including 6 upregulated miRNAs (including hsa-miR-34a and hsa-miR-455) and 5
downregulated miRNAs (including hsa-let-7f-1). All DE-miRs kept their
upregulation/downregulation pattern in the control, non-severe pneumonia and
severe pneumonia samples. Predicted target genes of DE-miRs in the subjects with
non-severe pneumonia vs. the control and the subjects with severe pneumonia vs.
the non-severe pneumonia group were markedly enriched in the adherens junction
and Wnt signaling pathways. KALRN, Ras homolog family member A (RHOA), beta
catenin (CTNNB1), RNA polymerase II subunit K (POLR2K) and amyloid precursor
protein (APP) were determined to encode crucial proteins in the PPI network
constructed. KALRN was predicted to be a target of hsa-mir-200b, while RHOA,
CTNNB1, POLR2K and APP were predicted targets of hsa-let-7f-1. The results of the
present study demonstrated that hsa-let-7f-1 may serve a role in the development
of cancer and the Notch signaling pathway. Conversely, hsa-miR-455 may be an
inhibitor of pneumonia pathogenesis. Furthermore, hsa-miR-200b might promote
pneumonia via targeting KALRN.
PMID- 28413463
TI - Diagnostic value of neutrophil gelatinase-associated lipocalin for renal injury
in asphyxiated preterm infants.
AB - The aim of the present study was to analyze the diagnostic value of neutrophil
gelatinase-associated lipocalin (NGAL) in renal injury in asphyxiated preterm
infants. In total, 48 cases of asphyxiated preterm infants, 45 cases of premature
infants and 45 cases of normal newborn infants were included in the study. Using
ELISA we evaluated the level of urine NGAL, kidney injury molecule-1 (KIM-1),
cystatin C (Cys-C) and serum creatinine (Scr). We also calculated the estimated
glomerular filtration rate (eGFR). Our results showed that NGAL, KIM-1 and Cys-C
levels in the group of asphyxiant renal injury within 24 and 48 h were markedly
higher than the other two groups (P<0.05), while changes in Scr and eGFR within
24 h were not significant (P>0.05). Scr level in renal injury group within 48 h
was markedly elevated while the eGFR level was visibly reduced (P<0.05).
According to analysis of receiver operating characteristic curve, area under
curve for NGAL in the group of asphyxiant renal injury within 24 and 48 h was
significantly higher than KIM-1 and Cys-C. Susceptibility and specificity were
improved. In conclusion, diagnosis of renal injury in asphyxia neonates using
NGAL was more efficient compared to other methods.
PMID- 28413465
TI - Protective effects of baicalin on rabbit articular chondrocytes in vitro.
AB - Drug therapy is one of the typical treatments for post-injury inflammation of
cartilage. Traditional Chinese herbs have potential as treatments, as their long
history of clinical application has demonstrated they are effective and induce
minimal side effects. Baicalin is a traditional Chinese medicine that has been
used to treat inflammation, fever, ulcers and cancer for hundreds of years.
Previous studies have demonstrated that baicalin may decrease levels of
interleukin-1beta and suppress the expression of type-I collagen, thus
attenuating cartilage degeneration. In the present study, the effect of baicalin
on chondrocytes was assessed by examining the morphology, proliferation,
extracellular matrix (ECM) synthesis and cartilage-specific gene expression of
chondrocytes. The results indicated that baicalin may promote the proliferation
of articular chondrocytes, secretion of cartilage ECM and collagen type II,
aggrecan and SRY box (Sox) 9 gene upregulation. The expression of collagen I, a
marker of chondrocyte dedifferentiation, was downregulated by baicalin;
therefore, baicalin may maintain the phenotype of chondrocytes. Within the
recommended concentrations of baicalin ranging from 0.625-6.25 umol/l cell
proliferation was increased and a 1.25 umol/l dose of baicalin exerted the most
positive effect on articular chondrocytes. The results of the present study may
therefore indicate that baicalin may be used as a novel agent promoting the
repair of articular cartilage damage.
PMID- 28413466
TI - Analysis of missed diagnosis of orbital foreign bodies.
AB - A clinical analysis of diagnosis was performed as well as the management of
orbital foreign bodies, to investigate the methods to avoid missed diagnosis. A
total of 15 cases of an orbital foreign body was reviewed, and for these cases,
the clinical manifestation, imaging data and operative situation were studied.
Among the patients, 4 cases turned out to have wooden, 3 metallic, 2 glass, 2
bones, and 4 other foreign bodies. Twelve cases had received debridement and
suture before our management, and 1 foreign body was treated more than once. In
conclusion, detailed traumatic history and imaging examination are necessary for
the diagnosis of orbital foreign bodies, while prompt diagnosis, accurate
location and professional surgical skills are important for the treatment.
PMID- 28413464
TI - Anti-climacterium effects of pomegranate concentrated solutions in ovariectomized
ddY mice.
AB - In the present study, the complex anti-climacterium potential of standardized
pomegranate concentrated solution (PCS) was investigated using bilateral
ovariectomy (OVX) female ddY mice. Changes in body weight and gain during
experimental periods, food consumption, serum estradiol levels, total body and
abdominal fat densities, abdominal fat pads, and uterus weights were observed,
along with the histopathology of abdominal fat pads and uterus for anti-obesity
and estrogenic effects. In addition, liver weights, serum aspartate
aminotransferase (AST), alanine aminotransferase (ALT) levels, and
histopathological inspections were performed to explore the hepato-protective
effects. Serum total cholesterol (TC), low density lipoprotein (LDL), high
density lipoprotein, and triglyceride (TG) levels were monitored for
hypolipidemic effects with total body and femur mean bone mineral density (BMD),
right femur wet, dry and ash weights, strength, serum osteocalcin, bone-specific
alkaline phosphatase (bALP) contents, and histological and histomorphometrical
analyses for anti-osteoporosis activity. As a result of OVX, notable increases in
body weight and gains, food consumption, abdominal fat mass densities, weights of
abdominal fat pads deposited in the abdominal cavity, and serum AST, ALT, TC,
LDL, TG, and osteocalcin levels were observed, along with decreases in the
uterus, liver, and femur weights, mean total body and femur BMD, femur strength,
serum bALP, and estradiol levels. In addition, marked hypertrophic alterations in
adipocytes located in the deposited abdominal fat pads, liver steatosis, uterine
disused atrophic changes, and decreases in bone mass and structures of the femur
were also observed in OVX control mice with significant increases in bone
resorption markers based on histopathological and histomorphometrical analysis.
However, these estrogen-deficient climacterium symptoms were significantly
(P<0.05 or P<0.01) inhibited after 84 days of continuous treatment with estradiol
and PCS (1, 2 and 4 ml/kg), respectively. The present results suggested that PCS
was able to effectively inhibit or refine the climacterium symptoms, including
obesity, hyperlipidemia, hepatic steatosis, and osteoporosis, induced by OVX in
ddY mice.
PMID- 28413467
TI - Calcitonin gene-related peptide protects type II alveolar epithelial cells from
hyperoxia-induced DNA damage and cell death.
AB - Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive
oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related
peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome
activation. However, the role of CGRP in DNA damage during hyperoxia is unclear.
Therefore, the aim of the present study was to investigate the effects of CGRP on
DNA damage and the cell death of alveolar epithelial type II cells (AEC II)
exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat
lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the
specific CGRP receptor antagonist CGRP8-37. The cells were evaluated using
immunofluorescence to examine surfactant protein-C and ROS levels were measured
by probing with 2',7'-dichlorofluorescin diacetate. The apoptosis rate and cell
cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by
western blotting analysis of activated caspase 3. The DNA damage was confirmed
with immunofluorescence of H2AX via high-content analysis. The ROS levels,
apoptotic cell number and the expression of gammaH2AX were markedly increased in
the hyperoxia group compared with those in the air group. Concordantly, ROS
levels, apoptotic cell number and the expression of gammaH2AX were significantly
lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in
the hyperoxia or CGRP8-37/O2 groups. CGRP was concluded to protect lung
epithelium cells against hyperoxic insult, and upregulation of CGRP may be a
possible novel therapeutic target to treat hyperoxic lung injury.
PMID- 28413468
TI - Antitumor effect of sunitinib in human prostate cancer cells functions via
autophagy.
AB - The aim of the present study was to explore sunitinib-induced autophagic effects
and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP
human prostate cancer cell lines. Cells were exposed to escalating doses of
sunitinib treatment and subsequent cell viability and cell cycle analyses were
performed to evaluate the inhibitory effect of sunitinib in vitro.
Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3
(LC3) puncta was employed to assess autophagy levels after sunitinib treatment.
Western blot analysis was performed to evaluate variations in the levels of LC3,
sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian
target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved
caspase-3 proteins. The present study revealed that sunitinib treatment inhibited
cell growth and triggered autophagy in a dose-dependent manner in both cell
lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K
signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase
inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3
methyladenine enhanced apoptosis and exhibited improved cell viability, which
indicated that sunitinib induces not only apoptosis but also autophagic cell
death in prostate cancer cell lines. These results may lead to an improved
understanding of the mechanism of sunitinib's cytotoxic action and may provide
evidence that combined sunitinib autophagy-regulating treatment may be of benefit
to anti-prostate cancer therapy.
PMID- 28413469
TI - Repairing effects of ICAM-1-expressing mesenchymal stem cells in mice with
autoimmune thyroiditis.
AB - The aim of the present study was to determine the repairing effects of
intercellular adhesion molecule (ICAM)-1-expressing mesenchymal stem cells (MSCs)
in mice with autoimmune thyroiditis. Following induction of an experimental
autoimmune thyroiditis (EAT) model, mice were randomly divided into the following
groups (n=10 each): i) Normal control; and experimental groups that were subject
to EAT induction, including ii) EAT model; and iii) primary MSC; iv)
C3H10T1/2/MSC; v) C3H10T1/2-MIGR1/MSC; and vi) C3H10T1/2-MIGR1-ICAM-1/MSC, which
were all administered the relevant cells. MSCs were administered via the caudal
vein. A blood sample was harvested from the angular vein of each animal 28 days
post-treatment and ELISA was used to determine the serum total triiodothyronine,
total thyroxine (T4), thyroid-stimulating hormone (TSH), anti-thyroid peroxidase
(TPOAb), anti-thyroid microsomal (TMAb) and anti-thyroglobulin (TGAb) antibodies.
Hematoxylin and eosin staining was performed to evaluate injury of the thyroid
gland by determining the size of the follicle, inflammatory infiltration,
colloidal substance retention and epithelial injury. Reverse transcription
quantitative polymerase chain reaction was performed to determine the mRNA
expression of interleukin (IL)-4, IL-10, IL-17 and interferon (INF)-gamma.
Western blot analysis was performed to determine the expression of p38 mitogen
activated protein kinase (p38) and extracellular signal-regulated kinase (ERK).
To observe cellular migration in vivo, mice were divided into the following
groups, (n=10 each), which were subject to EAT induction: i) CM-DiI-labeled
primary MSC; ii) CM-DiI-labeled C3H10T1/2/MSC; iii) CM-DiI-labeled C3H10T1/2
MIGR1/MSC; and iv) CM-DiI-labeled C3H10T1/2-ICAM-1/MSC, which were all
administered the relevant cells via the caudal vein. C3H10T1/2-ICAM-1/MSCs were
able to ameliorate the expression of T4, TSH, TPOAb, TMAb and TGAb in vivo,
attenuate thyroid follicle injury and decrease the splenic index in mice. They
were also able to ameliorate the mRNA expression of IL-4, IL-10, IL-17 and INF
gamma, and the modulation of the P38 and ERK-signaling pathways in the mouse
spleen. Furthermore, ICAM-1 overexpression was able to modulate the nesting of
MSCs in the thyroid gland and lung. These findings suggest that C3H10T1/2-ICAM
1/MSC may affect the differentiation, proliferation and migration of immunocytes
through modulating the p38 and ERK signaling pathways, and that ICAM-1 may
modulate the immunoregulatory effects of MSCs by affecting the migration of MSCs
in vivo.
PMID- 28413470
TI - Identification of genes associated with the effect of inflammation on the
neurotransmission of vascular smooth muscle cell.
AB - Vascular smooth muscle cell (VSMC) accumulation and hypertrophy are common in
vascular disorders, and inflammation has a crucial role in the development of
these diseases. To investigate the effect of inflammation on the
neurotransmission of VSMC, bioinformatic analysis was performed, following next
generation sequencing. Genes of lipopolysaccharide (LPS)-treated A7r5 cells and
phosphate-buffered saline (PBS)-treated A7r5 cells were sequenced via next
generation sequencing, and each assay was repeated three times. Differentially
expressed genes (DEGs) were obtained using the NOISeq package in R. Subsequently,
their potential functions were predicted by functional and pathway enrichment
analyses using the Database for Annotation, Visualization and Integrated
Discovery online tool. Interaction relationships of the proteins enriched in
pathways associated with neurological diseases, the proteins which had
interaction relationships with adrenoceptor alpha 1D (ADRA1D) or calcium voltage
gated channel subunit alpha1 S (CACNA1S), separately, were obtained from STRING,
and protein-protein interaction (PPI) networks were constructed using Cytoscape
software. A total of 2,038 DEGs, including 1,094 upregulated and 944
downregulated genes in the LPS treatment group were identified when compared with
the control group. Enrichment analyses showed that NADH:Ubiquinone Oxidoreductase
Core Subunit V2 (NDUFV2) was involved in several neurological diseases, including
oxidative phosphorylation, Alzheimer's disease, Parkinson's disease and
Huntington's disease. Furthermore, NDUFV2 (degree, 20) had a higher degree in the
PPI network for DEGs enriched in pathways associated with neurological diseases.
In the PPI network for ADRA1D, CACNA1S and the DEGs interacting with them,
prohibitin (PHB), oxytocin receptor (OXTR), collapsin response mediator protein 1
(CRMP1) and dihydropyrimidinase like 2 (DPYSL2) had interaction relationships
with both ADRA1D and CACNA1S. To conclude, the present study revealed that
NDUFV2, PHB, OXTR, CRMP1 and DPYSL2 may have key roles in the effect of
inflammation on neurotransmission of VSMC.
PMID- 28413471
TI - Influence of camel milk on the hepatitis C virus burden of infected patients.
AB - Hepatitis C virus (HCV) infection represents a world health problem and no
protective vaccine or effective drug currently exists. For economic reasons, many
patients use traditional medicines to control the infection. In Egypt, camel milk
is one of the traditional medicines widely consumed by patients infected with
HCV. The present study aimed to evaluate the efficacy of camel milk in the
treatment of patients infected with HCV. Whole camel milk from a local farm was
administered to patients for 4 months (250 ml/day/patient). Patient sera were
collected prior to and following camel milk drinking, and three markers were set
up for sera-evaluation. The three markers indicating the effect of camel milk on
HCV infection were: Liver function assays [alanine aminotransferase (ALT) and
aspartate aminotransferase (AST)]; a viral load assay; and anti-HCV antibodies
profile and isotyping against synthetic HCV epitopes. Camel milk demonstrated the
ability to improve general fatigue, health and liver function (ALT and AST
levels); ALT was reduced in ~88% of patients and AST was reduced in all patients
subsequent to drinking camel milk for four months. The majority of patients
responded positively to camel milk treatment; RNA viral load decreased in 13 out
of the 17 patients (76.47%) and one patient exhibited undetected viremia
following camel milk treatment. The anti-HCV antibodies profile and isotyping
were significantly decreased (P<0.05) in immunoglobulin (Ig)G1 following
treatment in 70-76% of patients. However, the treatment was ineffective in 23.53%
of patients who experienced no reduction in RNA viral load following treatment
with camel milk. In conclusion, whole camel milk treatment demonstrated efficacy
in vivo; the viral load in the majority of patient sera was reduced and the IgG
isotype profile was converted to Th1 immunity.
PMID- 28413472
TI - Anti-diabetic effect of Alpinia oxyphylla extract on 57BL/KsJ db-/db- mice.
AB - Diabetes mellitus is characterized by high blood glucose levels. Increased levels
of reactive oxygen species (ROS) may disrupt insulin signaling and result in
insulin resistance. The Alpinia oxyphylla extract (AOE) possesses powerful
antioxidant activity and may therefore inhibit the development of insulin
resistance. The objective of the present study was to determine the effects of
AOE on blood glucose, insulin and lipid levels in a type II diabetic nephropathy
animal model (C57BIKsj db-/db-). All experiments were performed on male C57BL/Ks
DB/DB and db-/db- mice that were left to acclimatize for 1 week prior to the
experimental period. AOE was administered to these mice at different dosages
(100, 300 and 500 mg/kg) for 8 weeks. The results demonstrated that AOE did not
affect mouse weight, while blood glucose concentrations were found to
significantly decrease in a dose-dependent manner (P<0.05). The effect of
administering 500 mg/kg AOE (AOE500) to db-/db- mice was tested further.
Treatment with AOE500 for 8 weeks led to improved glucose tolerance and reduced
plasma insulin concentrations (P<0.05), as well as a significant decrease in
triglyceride concentrations (P<0.05) and levels of total cholesterol (P<0.05) in
db-/db- mice. Furthermore, treatment with AOE500 decreased the concentration of
malondialdehyde, elevated the concentration of glutathione and increased the
activities of the antioxidant enzymes superoxide dismutase and peroxidase
(P<0.05) in the livers of db-/db- mice. Meanwhile, AOE-treated mice exhibited
significantly reduced urine albumin, creatinine and blood urea nitrogen excretion
(P<0.05). In parallel, the upregulated expression of phosphatase and tensin
homolog (PTEN) in the liver and kidneys of db-/db- mice was impaired following
AOE500 treatment. The results of the present study suggest that AOE regulates
blood glucose and lipid levels and improves renal function by mediating oxidative
stress and PTEN expression at the onset of type II diabetes mellitus.
PMID- 28413473
TI - MicroRNA-200c suppresses cell growth and metastasis by targeting Bmi-1 and E2F3
in renal cancer cells.
AB - The aim of the present study was to evaluate the functions of miR-200c in the
regulation of tumor growth and metastasis in renal cancer cells, and to
investigate the underlying mechanisms. In this study, miR-200c was up- and
downregulated in two renal cancer cell lines, namely ACHN and A498, and the
proliferation, colony formation, migration and invasion of the cells were
measured. The expression levels of various mRNAs and proteins were then analyzed
using reverse transcription-quantitative polymerase chain reaction and western
blotting, respectively. It was found that miR-200c suppressed proliferation,
migration and invasion of the renal cancer cells and, conversely, the inhibition
of endogenous miR-200c resulted in increased cell proliferation and metastasis.
Furthermore, a luciferase reporter assay revealed that miR-200c directly targeted
the 3' untranslated regions of the oncogenes B-cell-specific Moloney murine
leukemia virus insertion site 1 (Bmi-1) and E2F transcription factor 3 (E2F3)
mRNAs, reduced the expression of Bmi-1 and E2F3 and regulated the expression of
downstream genes, including E-cadherin, N-cadherin, vimentin, p14 and p16. These
results indicate a tumor suppressor role for miR-200c in renal cancer cells via
the direct targeting of Bmi-1 and E2F3.
PMID- 28413474
TI - Obesity contributes more to increasing ApoB/ApoA1 ratio than hyperandrogenism in
PCOS women aged 20-38 years in China.
AB - We investigated the association between the apolipoprotein B
(ApoB)/apolipoprotein A1 (ApoA1) ratio and insulin resistance (IR), metabolic
syndrome (MS) and its components in Chinese polycystic ovary syndrome (PCOS)
adults. We also examined whether hyperandrogenism is involved in obesity-related
metabolic abnormalities in a cohort of patients. A clinical cross-sectional study
consisting of 532 Chinese PCOS adults aged 20-38 years was designed. Each subject
underwent a physical examination and laboratory evaluation. We found that the
ApoB/ApoA1 ratio was significantly higher in patients with MS compared to those
without MS. This test provided 83.6% sensitivity and 67.6% specificity with a
threshold value of 0.60 in MS. The ApoB/ApoA1 ratio increased significantly as
the number of MS components increased. After adjusting for age, the patients with
MS or IR were more likely to be in the high ApoB/ApoA1 group, and the ApoB/ApoA1
ratio was associated significantly with each of the MS components, high free
testosterone (FT), and high free androgen index (FAI). After adjusting for age
and body mass index (BMI), the association persisted for all factors excluding
high blood pressure (BP), high fasting plasma glucose (FPG), high FT, and high
FAI. Therefore, the ApoB/ApoA1 ratio was strongly associated with IR, MS and its
components, high FT, and high FAI. A high ApoB/ApoA1 ratio appears to be a good
predictive marker of MS in Chinese PCOS adults. Obesity, especially central
obesity, contributes more to increasing ApoB/ApoA1 ratio than increased BP, FPG,
FT and FAI in this cohort of PCOS patients.
PMID- 28413475
TI - Evaluation of the role of human beta-defensin 3 in modulation of immunity and
inflammatory response after knee replacement.
AB - The present study investigated the value of human beta-defensin 3 (HBD-3) in
adjusting the immunity and inflammatory response of T lymphocytes in the body
after knee replacement. Sixty-four cases of knee replacement patients were
successively selected and randomly divided into the control group and the
observation group each with 32 cases. Once a day, for 7 days, patients in the
control group were injected with placebo saline solution in the articular cavity.
Levels of Th1 and/Th2, interleukin (IL)-2 and IL-10, tumor necrosis factor (TNF)
alpha, toll-like receptor (TLR)-4, and alkaline phosphatase (ALP) were compared
one month later, and implant infection rates were compared within 1-year follow
up. Compared with patients in the control group, the levels of Th1 and Th1/Th2 in
the observation group significantly increased, yet their Th2 decreased. The
levels of IL-2 and TNF-alpha were also observed to be significantly elevated, yet
IL-10 decreased. Furthermore, their TLR-4 and ALP levels were significantly
higher. Three cases of implant-related infection occurred in the control group
and 1 case in the observation group. In conclusion, HBD-3 could adjust the
immunity and inflammatory response of cells in the body after knee replacement,
possibly playing an important role in implant-related infection.
PMID- 28413476
TI - The mechanism of human beta-defensin 3 in MRSA-induced infection of implant drug
resistant bacteria biofilm in the mouse tibial bone marrow.
AB - The mechanism of human beta-defensin 3 (HBD-3) in methicillin-resistant
Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria
biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague
Dawley rats with average weight of 230 g were selected to construct the infection
model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left
tibial bone marrow. The drugs were intraperitoneally injected after 24 h
medullary cavity infection, and the experimental groups included the model group,
HBD-3 group, and vancomycin group (20 rats in each group). The model group was
injected with 10 ml saline, HBD-3 group was injected with 10 ml of 8 ug/ml (1
MIC) and vancomycin group was injected with 10 ml of 0.5 ug/ml (1 MIC), five
animals in each group were sacrificed on the 1, 7, 14 and 21 days, respectively.
Observation was carried out on whether there was swelling and purulent secretion
on the local wound; 1 ml venous sinus blood of eye socket was collected for blood
routine examination and blood culture, and the laser scanning confocal microscopy
was used to observe the morphology of the biofilm on the implant surface and the
number of viable bacteria. Immunohistochemical staining was adopted to test the
expression of nuclear factor-kappaB (NF-kappaB) and toll-like receptor 4 (TLR-4),
and ELISA method was used to test interleukin-10 (IL-10), tumor necrosis factor
alpha (TNF-alpha), IL-1alpha and interferon-gamma (INF-gamma)-inducible protein
10 (IP-10) expression levels. There was no death due to infection in the HBD-3
group or vancomycin group, 1 case with significant wound swelling was found,
respectively, in each group, but there was no purulent secretion. The percentage
of the total white blood cells and neutrophil granulocytes as well as the biofilm
morphology and the number of viable bacteria in the model group was gradually
increased with time, while those in the HBD-3 group and vancomycin group were
decreased with time. The comparative difference among groups was statistically
significant (P<0.05); those in the HBD-3 group and vancomycin group at each time
point was decreased significantly compared with the model group, and the
difference among groups was statistically significant (P<0.05), but in terms of
the comparison between the HBD-3 group and vancomycin group, the difference was
not significantly different (P>0.05). The NF-kappaB and TLR-4 expressions in the
model group and vancomycin group were not significantly changed at each time
point, those in the HBD-3 group began to increase on the 1st day, and reached the
peak on the 7th day and began to decline on the 14th day, and the comparative
difference at each time-point was statistically significant (P<0.05); those in
the HBD-3 group were significantly higher than the model group and vancomycin
group at each time-point and the difference was statistically significant
(P<0.05). The IL-10, TNF-alpha, IL-1alpha, and IP-10 expressions in the model
group at each time were significantly higher than the other two groups and the
difference was statistically significant (P<0.05); in terms of the comparison
between the HBD-3 group and vancomycin group, the difference was not
statistically significant (P>0.05). In conclusion, beta-defensin 3 can inhibit
the bacterial growth by regulating inflammation and immune responses in the MRSA
induced implant drug-resistant bacteria biofilm infection in the mouse tibial
bone marrow.
PMID- 28413477
TI - Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral
ischemia-reperfusion injury in vivo and in vitro.
AB - Isoquercetin has exhibited a wide range of therapeutic properties, including
antioxidant, anti-inflammatory and anti-allergic activities. The aim of the
present study was to investigate the effect of isoquercetin on rats with 2 h
middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect
of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected
to oxygen-glucose deprivation followed by reoxygenation (OGD/R). In vivo, the
rats treated with isoquercetin exhibited a lower degree of neurological
dysfunction and smaller infarct volume than the vehicle-treated rats. In vitro,
it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis,
lactate dehydrogenase release and reduction in cell viability. Additionally,
isoquercetin induced the upregulation of nuclear factor erythroid 2-related
factor 2 gene and protein expression, and increased extracellular signal
regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2
pathway may contribute to the neuroprotective effect of isoquercetin against
OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest
the potential importance of isoquercetin in the treatment of ischemia/reperfusion
related brain injury and associated diseases.
PMID- 28413479
TI - Inhalative and intravenous stimulation of soluble guanylate cyclase reduces
pulmonary vascular resistance and increases cardiac output in experimental septic
shock.
AB - The effects of inhaled and intravenous application of a guanylate cyclase
stimulator (BAY 41-8543) on pulmonary vascular resistance (PVR) and cardiac
output (CO) were investigated in an experimental model of septic shock. Following
induction of septic shock, anaesthetized pigs (n=31) were randomly place into two
groups receiving different interventions. Animals in the first group received
intravenous BAY 41-8543 (0.6 mg), inhalative BAY 41-8543 (6 mg) or a placebo. In
the second group, the dosage of BAY 41-8543 was increased two-fold or combined
with inhalation of nitric oxide (iNO). Intravenous and inhaled administration of
BAY 41-8543 resulted in a significantly (P<0.05) reduced PVR and increased CO
compared with the placebo. Increasing the dosage of BAY 41-8543 or combining it
with iNO did not further decrease PVR. The results of the present study indicate
that BAY 41-8543 effectively reduces PVR and increases CO in septic shock,
through inhaled or intravenous routes of administration.
PMID- 28413478
TI - Icariin improves osteoporosis, inhibits the expression of PPARgamma, C/EBPalpha,
FABP4 mRNA, N1ICD and jagged1 proteins, and increases Notch2 mRNA in
ovariectomized rats.
AB - Icariin (ICA) is a pharmacologically active flavonoid glycoside that shows
promise in the treatment and prevention of osteoporosis (OP). However, the
mechanisms underlying the anti-osteoporotic effects of ICA remain largely
unclear. The present study used quantitative polymerase chain reaction, western
blot and immunohistochemical analysis to examine the effects of ICA on several
key targets in the Notch signaling pathway in bone tissue in ovariectomized rats.
It was observed that ICA has a pronounced beneficial effect on OP rats and
inhibits the expression of peroxisome proliferator-activated receptor gamma
(PPARgamma), CCAAT/enhancer binding protein alpha (C/EBPalpha) and fatty acid
binding protein 4 (FABP4) mRNA. In addition, it was identified that ICA
downregulates the expression of notch1 intracellular domain (N1ICD) and Jagged1
proteins in bone tissue, and suppresses the effect of N1ICD on Notch2 mRNA
expression. It is proposed that ICA inhibits the differentiation of mesenchymal
stem cells into adipocytes by inhibiting the expression of PPARgamma, C/EBPalpha
and FABP4 mRNA via the Notch signaling pathway. In addition, it is proposed that
ICA inhibits the expression of Notch2 mRNA by suppressing the effect of N1ICD. In
conclusion, the results provide further mechanistic evidence for the clinical
efficacy of ICA in the treatment of OP.
PMID- 28413480
TI - Analysis of the mechanism by which nerve growth factor promotes callus formation
in mice with tibial fracture.
AB - The aim of the present study was to analyze the mechanism by which nerve growth
factor (NGF) promotes callus formation in mice with tibial fracture. NGF
transgenic homozygotic mice and NGF wild homozygotic mice were selected to
construct non-stabilized fracture model of tibia. The mice were sacrificed on
days 7, 14 and 21, respectively, and each group had a sample with 8 mice at each
point in time. X-ray radiography and safranin fast green were used to observe
fracture healing and in situ hybridization was used to examine the NGF mRNA
expression of tibia at each phase of fracture healing. Tartrate-resistant acid
phosphatase (TRAP) staining of callus tissue and the expression level of TRAP
mRNA were combined to observe osteoclast formation. COL2A1, a chondrocyte
differentiation-related gene in callus, and the mRNA level of SOX9 were combined
to observe chondrocyte differentiation. It was found that under X-ray
radiography, the fracture of NGF transgenic homozygotic mice healed in advance
(P<0.05). Cartilage and bone tissue were identified by safranin and fast green
staining. The residual cartilage on the callus tissue of NGF transgenic
homozygotic mice had decreased significantly (P<0.05). The NGF mRNA expression
level in each phase of callus formation of NGF transgenic homozygotic mice was
significantly higher than that of the wild group (P<0.05). The number of positive
cells in NGF-TRAP staining at each time point after fracture and the NGF mRNA
expression level was markedly higher than that of the wild group, and the
expression levels of COL2A1 and SOX9 mRNA were distinctively higher than that of
the wild group. In conclusion, NGF potentially improves the healing of tibial
fracture by osteoclast formation. Additionally, an increase in the number of
osteoblasts in the NGF transgenic homozygotic mice compared with the wild-type
mice may be achieved by cartilage differentiation due to NGF increasing the
COL2A1 and SOX9 mRNA expression levels.
PMID- 28413481
TI - Oxymatrine on Hsp90a expression and apoptosis in a model of lung ischemia
reperfusion injury.
AB - The protective effects of oxymatrine (OMT) on apoptosis and heat shock protein
90a (Hsp90a) expression in a rabbit model of lung ischemia-reperfusion injury
(LIRI) were investigated. The model of LIRI was established in rabbits and they
were randomly divided into two groups: The control group (group C, n=10), and
experimental group (further divided into groups E1, n=10; and group E2, n=10), to
measure the levels of malondialdehyde (MDA) and superoxide dismutase (SOD)
activity in lung tissue homogenates at several time points (T0, 0 min; T1, 60
min; T2, 120 min; T3, 180 min; and T4, 240 min), and to measures changes in lung
tissue wet/dry weight ratio (W/D), apoptosis index (AI), and Hsp90a expression
and organization at T2, T3 and T4. Comparing group C with groups E1 and E2, the
levels of SOD activity and MDA were not significantly different at T0 and T1
(P>0.05); W/D ratio and AI were significantly higher than in groups E1 and E2
(P<0.05, P<0.01); 120 min after LIR, MDA, W/D ratio, and AI were lower than in
groups E1 and E2 (P<0.05, P<0.01). MDA, W/D ratio and AI were lower in E2 than in
E1 (P<0.05), and SOD and Hsp90a expression increased (P<0.05). The ultrastructure
in group E showed less injury compared with group C. In conclusion, by scavenging
oxygen free radicals, OMT can inhibit apoptosis, increase Hsp90a expression, and
reduce the injury caused by lung ischemia reperfusion.
PMID- 28413482
TI - Dysfunction of the thymus in mice with hypertension.
AB - The aim of this study was to evaluate thymus function in mice with hypertension.
A total of 60 C57BL/6J mice were randomized into control, sham surgery and two
kidney, one-clip groups (n=20 in each). At 4 or 8 weeks after surgery, mice were
sacrificed, and blood, spleens, kidneys and thymuses were harvested. The results
of reverse transcription-quantitative polymerase chain reaction analysis revealed
that the mRNA levels of Forkhead box protein N1 (Foxn1) and autoimmune regulator
(AIRE) in the thymus tissue of mice from the HTN group were significantly lower
than those from the control group at 4 and 8 weeks (P<0.05). Foxn1 and AIRE
expression was also reduced in the sham surgery group at 4 weeks after surgery,
but had recovered 4 weeks later. Similar results were observed for the expression
of signal-joint T cell receptor excision circles and the percentages of T cell
subsets. The present study indicates that impaired thymus function is associated
with hypertension in mice, which suggests that thymus function may be a novel
target for the treatment of patients with hypertension.
PMID- 28413483
TI - Morphine and pregabalin in the treatment of neuropathic pain.
AB - The drugs that are currently available to treat neuropathic pain exhibit
inadequate efficacy and numerous adverse effects. The present study compared the
efficacy of combination therapy with pregabalin and morphine with that of each as
a single agent in patients with neuropathic pain. The primary measurement was
mean daily pain intensity. Secondary measurements included a pain questionnaire,
adverse effects, mood and quality of life. Combination therapy of morphine plus
pregabalin and morphine monotherapy were both more effective at reducing
neuropathic pain than pregabalin monotherapy. Furthermore, patients in the
combination group noted that their quality of life markedly improved from the
baseline, as compared with the patients in the other two groups. These findings
indicate that combination therapy with morphine and pregabalin may be used as a
valuable therapy for neuropathic pain.
PMID- 28413484
TI - Inhibitor kappaBalpha protein therapy alleviates severe pneumonia through
inhibition of nuclear factor kappaB.
AB - To investigate the effect of inhibitor kappaBalpha (IkappaBalpha) on severe
pneumonia and explain the mechanisms of nuclear factor kappaB (NF-kappaB), the
activation of NF-kappaB was induced in Sprague-Dawley (SD) rats infected with
Klebsiella pneumoniae (K. pneumoniae). The rats were then treated with differing
concentrations of IkappaBalpha protein. A histological analysis was performed to
compare the lung structure prior to and following treatment, and an
immunohistochemistry assay was used to detect NF-kappaB activity. In addition,
the expression of certain inflammatory factors was detected using a protein chip
assay. The severe pneumonia rat model was successfully produced and in model
rats, NF-kappaB was activated by K. pneumoniae. Following treatment with
IkappaBalpha, the activity of NF-kappaB was inhibited and pneumonia symptoms in
model rats were alleviated. Furthermore, the expression of a number of
inflammatory factors including tumor necrosis factor alpha (TNF-alpha),
interleukin 6 (IL-6), interferon gamma (IFN-gamma) and monocyte chemoattractant
protein-1 (MCP-1) were also inhibited. The current study demonstrates that NF
kappaB inhibition with IkappaBalpha protein therapy prevents the development of
pneumonia in a K. pneumoniae rat model. The therapeutic effect is indicated by
the responses of proinflammatory factors, including TNF-alpha, IL-6, IFN-gamma
and MCP-1.
PMID- 28413485
TI - Therapeutic efficacy of phentolamine in the management of severe hand, foot and
mouth disease combined with pulmonary edema.
AB - The aim of this study was to examine the effects of phentolamine on severe hand,
foot and mouth disease (HFMD) combined with pulmonary edema (PE). From May 2008
to December 2012, 53 children with severe HFMD plus PE were enrolled in the
treatment group, receiving phentolamine intravenously at a loading dose of 5
ug/kg/min. The control group comprised 52 children with the same disease who did
not receive phentolamine infusion. Data concerning creatine kinase (CK), CK-MB,
cardiac troponin I (cTnI), heart rate, systolic blood pressure (SBP) and the
duration of ventilation dependence and hospitalization were collected. Adverse
events were also recorded. It was found that the phentolamine-treated patients
exhibited significantly lower CK, CK-MB and cTnI levels, heart rate and SBP than
the controls (P<0.01 for all parameters). The average duration of ventilator
dependence and hospitalization was significantly shorter (P<0.01) in the
phentolamine group than in the control group. It was also found that the overall
mortality rate was lower in the phentolamine group (5.8%) than in the control
group (11.5%). No adverse events were observed in either group. Thus, these
results offer preliminary evidence that phentolamine reduces mortality and
relieves the symptoms of EV71-induced PE. Phentolamine is a potential therapeutic
agent for this highly lethal disorder.
PMID- 28413486
TI - Cigarette smoke extract promotes proliferation of airway smooth muscle cells
through suppressing C/EBP-alpha expression.
AB - Cigarette smoke has been considered a major contributor to the pathogenesis of
chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth
muscle layer has been observed to be markedly thickened and the proliferation of
airway smooth muscle cells (ASMCs) was therefore used by the present study as a
model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed
to various concentrations of CSE and the proliferation of the cells was analyzed
by an MTT assay. Furthermore, the expression levels of calreticulin and
CCAAT/enhancer-binding protein alpha (C/EBP-alpha) in CSE-stimulated ASMCs were
determined by polymerase chain reaction and western blot analyses. In addition,
the effects of RNA interference (RNAi) to knockdown calreticulin and/or C/EBP
alpha on ASMC proliferation were studied. CSE was found to promote the
proliferation of ASMCs, which was associated with increased expression of
calreticulin and decreased expression of C/EBP-alpha. Knockdown of calreticulin
resulted in the upregulation of C/EBP-alpha and inhibition of cell proliferation,
while simultaneous knockdown of C/EBP-alpha promoted cell proliferation. The
present study revealed that CSE promoted the proliferation of ASMCs, which was
mediated by inhibition of C/EBP-alpha. These findings shed new light on airway
remodeling in COPD and may provide novel approaches for therapies.
PMID- 28413487
TI - Vandetanib and ADAM inhibitors synergistically attenuate the pathological
migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF
mediated MAPK pathway.
AB - The extracellular signals induced by vascular endothelial growth factor (VEGF)
are implicated in choroidal neovascularization (CNV) and thus, are associated
with vision-limiting complications in the human retina. Vandetanib is an oral
anticancer drug that selectively inhibits the activities of VEGF receptor and
epidermal growth factor receptor tyrosine kinase; however, the effects of
vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been
studied. In the present study, a combined treatment of vandetanib and a
disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess
the regulation of Epstein-Barr virus (EBV)-infected ARPE19 cells (ARPE19/EBV)
migration as a model of CNV. Vandetanib suppressed the expression of the
mesenchymal markers ADAM10 and ADAM17 in ARPE19/EBV cells, and also upregulated
epithelial cell markers of the RPE cells, E-cadherin and N-cadherin. The
migratory activity of ARPE19/EBV induced by VEGF was efficiently blocked by
vandetanib. Furthermore, co-treatment with vandetanib and an ADAM10 inhibitor
(GI254023X) or ADAM17 inhibitor (Marimastat) synergistically prevented migration
and the expression of vimentin, Snail and alpha-smooth muscle actin by regulating
extracellular signal-regulated kinase and p38 mitogen-activated protein kinase.
These results suggest that a combination treatment of vandetanib and ADAM
inhibitors may be developed as a novel therapeutic regimen to control retina
neovascular disease.
PMID- 28413488
TI - The effects of GLP-1 analogues on pre-diabetes of the children.
AB - The aim of the study was to evaluate the clinical efficacy of glucagon-like
peptide-1 (GLP-1) analogues in children of pre-diabetes to delay or reverse the
development of pre-diabetes into the state of diabetes by early intervention.
Prospective and randomized controlled clinical trials were performed in 42 cases
of newly diagnosed pre-diabetes in children. The sample size was randomly divided
into the two groups. The first group included 21 subjects comprising the
lifestyle intervention group, i.e., control group, and the second group included
21 subjects comprising the lifestyle intervention+GLP-1 analogues liraglutide
group, i.e., observation group. Interventions carried out lasted 3 months. A
review of intervention was carried out at 1 month and after 3 months. Medical
examinations were carried out at the the time following diagnosis with pre
diabetes and after the intervention of 3 months. The medical test examinations
included the fasting blood glucose (FPG), 2-hour postprandial blood glucose
(2hPG), detection of glycated hemoglobin A1c (HbA1C), total cholesterol (TC),
triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density
lipoprotein cholesterol (HDL-C), body mass index (BMI), insulin resistance (IR)
and the islet cell functions. After 1 month of intervention, the observation
group exhibited a better control on FPG and 2hPG compared with the control group
(P<0.05). After 3 months of the intervention, FPG and 2hPG levels of the
observation group were significantly lower than those of the control group
(P<0.01). The levels of HbA1C, TC, TG, LDL-C, HDL-C, and BMI of the observation
group were statistically better controlled, when compared with the control group
after the intervention of 3 months. The IR index of the observation group was
significantly decreased compared to that of the control group (P<0.05) and the
islet function index of the beta-cell of the observation group showed
statistically higher values than that of the control group (P<0.05). In
conclusion, GLP-1 analogues are a better regulator of blood sugar levels,
effectively improve lipid profile, body mass, IR and islet beta-cell function.
Furthermore, GLP-1 analogues opens up a new way to intervene pre-diabetes in
children.
PMID- 28413489
TI - Retrospective review of epidemic viral pneumonia cases in Turkey: A multicenter
study.
AB - Influenza A (H1N1) caused its first pandemic in 2009 in USA and Mexico. Since
then, clinicians have exercised great care in order to make an early diagnosis of
viral pneumonias. This is due in part to pandemic influenza A infection having
greater impact on populations <65 years old than other viral strains, including
seasonal influenza. Chest radiographies of those affected displayed a rapid
progression of patchy infiltrates, and a large proportion of individuals required
admission to intensive care units (ICU). Despite efforts, patients infected with
the virus had a high mortality rate. The present multicenter study aimed to
retrospectively evaluate the clinical, demographic and prognostic characteristics
of patients diagnosed with epidemic viral pneumonia in Turkey. A total of 92
patients were included in the study. The Student's t-test and Chi-square tests
were performed to analyze quantitative data, assuming a normal distribution, and
to analyze qualitative data, respectively. Stepwise logistic regression was used
to evaluate the effects of demographic variables and laboratory values on the
virus mortality rate. The male/female ratio was 42/50 and the mean age was
48.74+/-16.65 years. A total of 69 (75%) patients were unvaccinated against
influenza. The most common symptoms were cough (87%) and fever (63%). Chest
computed tomography showed peripheral patchy areas of the lungs of ground glass
density in 38 patients (41.3%). A total of 22 (59.4%) patients had H1N1, 5
(12.5%) patients had influenza B, and 38 (41.3%) patients met the criteria for
admission to the ICU. Of these patients, 20 (52.63%) were monitored with a
mechanical ventilator, with a noninvasive ventilator being adequate for 10
(26.32%) of patients. The length of stay in the ICU was 6.45+/-5.97 days and the
duration of mechanical ventilation was 5.06+/-4.69 days. A total of 12 (13.04%)
patients in the ICU succumbed. Logistic regression analysis revealed that among
the parameters possibly associated with mortality, being an active smoker
increased the risk of mortality 7.08-fold compared to other groups (P=0.005). In
conclusion, viral pneumonia remains a significant health problem during the
winter period. Considering the high number of ICU admissions and high rate of
mortality for patients in the present study, earlier initiation of antiviral
therapy is necessary. Active smoking increased mortality in viral pneumonia.
PMID- 28413490
TI - Noninvasive cumulative axial load may induce intervertebral disc degeneration-A
potential rabbit model.
AB - Intervertebral disc degeneration (IDD) is considered to be the main cause of many
spinal disorders; however, its underlying pathophysiology is not clearly
understood. Recent studies indicate that excessive mechanical loading may serve a
major role in the initiation of IDD. The aim of the present study was to explore
the effect of noninvasive cumulative axial loading on the intervertebral discs of
the lumbar spine using a novel rabbit model. Rabbits in the experimental group
were placed into individual tubes specifically designed to force maintenance of
an upright posture and were loaded with a heavy collar to increase the
intradiscal pressure of their lumbar spine. Radiograph imaging and magnetic
resonance imaging (MRI) was performed every 4 weeks to provide evidence of disc
degeneration. At the end of the experiment, the animals were sacrificed and disc
specimens were harvested for quantitative polymerase chain reaction and
histological analysis. MRI results revealed significant and progressive
reductions in the signal intensities of lumbar discs in the experimental group
compared with the control group throughout the 14-week study period. The
expression level of type I collagen was significantly increased and the
expression levels of type II collagen and aggrecan were significantly decreased
in the experimental group compared with the control group (P<0.05). Histological
examination revealed marked structural changes in the experimental group,
including fibrocartilage-like tissue ingrowth and accelerated fibrotic changes of
the nucleus pulposus. The results of the present study indicate that noninvasive
cumulative axial load is able to induce accelerated degenerative changes in
rabbit lumbar discs, which may provide useful information for the establishment
of a novel animal model of IDD for the research of IDD in humans.
PMID- 28413491
TI - Upregulated unique long 16 binding protein 1 detected in preeclamptic placenta
affects human extravillous trophoblast cell line (HTR-8/SVneo) invasion by
modulating the function of uterine natural killer cells.
AB - Well-controlled trophoblast invasion at the maternal-fetal interface is crucial
for normal placentation and successful pregnancy, otherwise pathological
conditions of pregnancy occur, such as preeclampsia. In previous studies, it has
been demonstrated that unique long 16 binding protein (ULBP)1, a ligand for the
natural-killer group (NKG)2D receptor on uterine natural killer (uNK) cells, is
upregulated in the placenta in patients with preeclampsia. As they are present on
the majority of the decidua, uNK have an important role in pregnancy. The aim of
the present study was to determine the role of ULBP1 in trophoblast cell
invasion, which is closely associated with the occurrence of preeclampsia. In the
present study, ULBP1 expression levels in placentas collected after cesarean
section from women with preeclampsia and normal pregnant women were determined by
immunohistochemistry, reverse transcription-quantitative polymerase chain
reaction and western blotting. The effects of ULBP1 on extravillous trophoblast
cell line (HTR-8/SVneo) invasion mediated via uNK cells and the underlying
mechanisms were investigated. mRNA and protein expression levels of ULBP1 were
significantly upregulated (P<0.05) in preeclamptic placentas compared with normal
controls. ULBP1 inhibited HTR-8/SVneo cells via the regulation of biological
functions of uNK cells, including the downregulation of NKG2D expression on uNK
cells and the stimulation of production of cytokines and chemokines that affect
extravillous cytotrophoblast invasion by uNK cells. ULBP1 may have an important
role in the pathophysiology of preeclampsia through the modification of
biological functions of uNK cells, which may affect trophoblast invasion.
PMID- 28413492
TI - Immunogenicity of insulin-producing cells derived from human umbilical cord
mesenchymal stem cells.
AB - Mesenchymal stem cells (MSCs) have been considered as hypo-immunogenic and
immunosuppressive. However, a thorough understanding of the immunological
properties after MSC differentiation in vitro and in vivo has not been reached.
We asked whether it would be immunogenic after differentiation or influenced by
the immune microenvironment after transplantation. In different disease models,
the immunological changes of MSCs after differentiation greatly varied, with
contradicting results. In order to clarify this, we used a modified four-step
induction method to induce human umbilical cord MSCs (hUCMSCs) to differentiate
into insulin-producing cells (IPCs), and investigate the immunological changes
after differentiation and immune reactions after transplantation into diabetic
mice. We found that the induced IPCs are hypo-immunogenic, lacking HLA-DR, CD40
and CD80 expression. Of note, we observed immune cell infiltration to peritoneal
cavity and left kidney capsule after local transplantation of induced IPCs. This
indicated that hUCMSC-derived IPCs maintained hypo-immunogenic in vitro, but
became immunogenic after transplanting to the host, possibly due to the changes
of immune microenvironment and thereafter immunological enhancement and immune
cell infiltration.
PMID- 28413493
TI - TGF-beta1 and TIMP1 double directional rAAV targeted by UTMD in atherosclerotic
vulnerable plaque.
AB - In the present study, we determined whether ultrasound-targeted microbubble
destruction (UTMD) combined with dual targeting of transforming growth factor
(TGF)-beta1 and tissue inhibitors of metalloproteinase (TIMP) 1 recombinant adeno
associated virus (rAAV) can stabilize atherosclerotic vulnerable plaques. First,
we used rabbit model to detect the TGF-beta1/TIMP1 virus therapy result. H&E
staining was used to evaluate the tissues. The protein levels of TGF-beta1 and
TIMP1 were detected in rabbit models. The THP-1 cells were induced into
macrophages, and transfected with TGF-beta1 and TIMP1 rAAV under optimized UTMD.
The expression of TGF-beta1 and TIMP1 was measured by RT-PCR and western
blotting. We found that the apoptotic rates were induced when compared to the
control group. The rAAV virus group showed a significant decrease in the p-ERT
and p-AKT expression. These data support the hypothesis that TGF-beta1 and TIMP1
are crucial in the regulation of atherosclerotic plaques.
PMID- 28413494
TI - Preoperative QCT assessment of femoral head for assessment of femoral head bone
loss.
AB - We quantified differences in trabecular volumetric bone mineral density (BMD) of
the femoral head between patients with proximal femoral fractures and healthy
subjects in the control group by using quantitative computed tomography (QCT)
with the purpose of providing guidance for the choice of head screw in the
intramedullary nail fixation. Participants suffering from intertrochanteric
fractures (n=536 patients) were recruited. In addition, 497 fracture-free, age
matched cases were considered as the control group. The volumetric BMD of
different regions of interest (ROI) in the proximal femur scanned by QCT were
analyzed between the fracture and control groups. BMD of proximal femur in the
fracture group was markedly lower than that in the control group. There were
significant differences at distinct regions for male and female between the two
groups. Furthermore, the trend of BMD changes among the femoral head, femoral
neck and intertrochanter were not parallels in terms of their average value. In
conclusion, osteoporosis has been demonstrated to be a main risk factor of the
proximal femoral fracture. BMD value of proximal femur was often inconsistent
with that of femoral head. Given this, preoperative QCT assessment plays an
important role in choosing proper head screw in the intramedullary nail fixation.
PMID- 28413495
TI - Perioperative application of salvianolate on oxidative stress and plasma IMD/ADM2
in patients with acute myocardial infarction undergoing PCI.
AB - The present study was conducted to investigate the effects of salvianolate on
perioperative oxidative stress and plasma Intermedin/adrenomedullin 2 (IMD/ADM2)
in patients with acute myocardial infarction (AMI) undergoing percutaneous
coronary intervention (PCI). The clinical data of 108 patients with AMI treated
by PCI were retrospectively analyzed. According to the use of salvianolate in
perioperative period, the patients were divided into the study group (n=62) and
the control group (n=46). The control group was given routine treatment while the
study group was given routine treatment combined with intravenous infusion of
salvianolate (200 mg administered once at 24 h before operation, once/day after
operation, 1 week later, the curative effect was observed). The changes in levels
of hemodynamic indexes [fibrinogen (FIB), platelet aggregation rate (PAG), plasma
viscosity, packed-cell volume (PCV)], oxidative stress indexes [superoxide
dismutase (SOD), glutathione peroxidase (GSH Px)], cardiac function indexes [left
ventricular ejection fraction (LVEF), cardiac output (CO)], related biochemical
indexes [high-sensitivity C-reactive protein (hs-CRP), N-terminal pro brain
natriuretic peptide (NT proBNP)] and plasma IMD/ADM2 in the two groups at 24 h
pre-operation and the 8th day postoperation were analyzed. On the 8th day post
operation, hemodynamic indexes such as FIB (3.3+/-1.0 and 3.9+/-0.9) g/l, PAG
(20.6+/-6.5 and 41.6+/-7.7)%, plasma viscosity (1.1+/-0.5 and 1.7+/-0.6)
mPa*s/120 s-1 and PCV (40.0+/-3.8 and 45.5+/-3.7)%, the related biochemical
indexes such as hs-CRP (55.1+/-4.8 and 79.3+/-5.3) mg/l and NT-proBNP (435.6+/
305.2 and 788.6+/-310.8) ng/l in the two groups were significantly decreased
compared to those pre-operation; the differences were statistically significant
(P<0.05). The oxidative stress indexes such as SOD (43.6+/-1.9 and 24.2+/-2.0)
U/ml and GSH-Px (822.6+/-13.52 and 742.6+/-62.6) enzyme activity unit, the
cardiac function indexes such as LVEF (45.1+/-3.5 and 41.9+/-3.3)% and CO (4.6+/
0.5 and 4.1+/-0.5) l/min and plasma IMD/ADM2 (163.5+/-20.2 and 144.2+/-22.5)
pg/ml in the two groups were significantly increased compared to those pre
operation; the differences were statistically significant (P<0.05). In
conclusion, applying intravenous infusion of salvianolate in patients with AMI
during perioperative period of PCI can effectively improve the oxidative stress
reaction and have positive effects on regulating plasma IMD/ADM2 level, which
promoted cardiac function recovery and enhances myocardial perfusion volume.
PMID- 28413496
TI - Clinical observation of the efficacy of Bevacizumab combined with argon green
laser in treating fundus macular edema.
AB - We studied the clinical efficacy of Bevacizumab combined with argon green laser
in treating fundus macular edema. From May 2009 to April 2013, 78 patients
seeking treatment for macular edema in the First Affiliated Hospital of Nanchang
University were enrolled in this study. Patients were randomly divided into two
groups: i) The experimental group (n=39) and the control group (n=39). Patients
in the experimental group were treated with Bevacizumab (Avastin(r)) combined
with argon green laser, and those in the control group were treated exclusively
with argon green laser. Therapeutic effects were compared, and postoperative
adverse reactions caused by both treatment methods were compared. Our results
showed that, after treatment, the macular foveal thickness was reduced noticeably
in both groups, while the therapeutic effect of combined treatment was more
prominent. Patients in the experimental group gained the best-corrected visual
acuity after one month of treatment, while patients in the control group achieved
that after three months of treatment. We concluded that the use of Avastin(r)
combined with argon green laser was safe and effective. Visual acuity was
improved obviously with minimum adverse reactions.
PMID- 28413497
TI - Antibiotic de-escalation principle in elderly patients with chronic obstructive
pulmonary disease complicated with severe pneumonia.
AB - The present study investigated the clinical effect of antibiotic de-escalation
therapy in elderly patients with chronic obstructive pulmonary disease (COPD)
complicated with severe pneumonia. According to the parity method of
hospitalization number, 86 cases were selected and divided into the observation
and control group with 43 cases each. Based on empirical antibiotic application,
levofloxacin and cephalosporin antibiotics were used in the control group. After
treatment for 3 days, the regimen was adjusted to antibiotics active against Gram
positive (G+) and Gram-negative (G-) bacteria such as the third or fourth
generation cephalosporin antibiotics, combined with aminoglycoside, or macrolide
antibiotics according to their effects. The treatment effects were re-evaluated
after 3-7 days. Finally, broad-spectrum antibiotics such as imipenem were chosen
or adjusted by bacterial cultures and drug sensitivity results in the control
group. Patients in the observation group were treated according to the principle
of antibiotic de-escalation therapy. Antibiotics active against G+ and G-
bacteria were chosen as the first round of medication. After 3 days, broad
spectrum antibiotics such as imipenem were added to the treatment regimen. After
7 days, the treatment was changed to narrow spectrum antibiotic administration if
the disease was in remission, and the antibiotic regimen was adjusted based on
bacterial culture and drug sensitivity results. The treatment results were
compared. The mechanical ventilation rate, antibiotic courses, number of
antibiotics used, and mortality of the observation group were significantly lower
than those in the control group (P<0.05). After treatment, lung function
improved, partial pressure of oxygen and blood oxygen saturation increased, and
partial pressure of carbon dioxide decreased in both groups. The improvement of
all of the above parameters were more significant in the observation group
(P<0.05). After treatment, the ratio of neutrophils over white blood cells and C
reactive protein levels of the two groups decreased, respiratory failure index
(RFI) increased, and the changes were significantly more pronounced in the
observation group (P<0.05). In conclusion, following the antibiotic de-escalation
principle to treat older patients with COPD complicated with severe pneumonia can
reduce the number of antibiotics required, improve lung function and clinical
effects, and is safe and effective.
PMID- 28413498
TI - Dynamic variations of the peripheral blood immune cell subpopulation in patients
with critical H7N9 swine-origin influenza A virus infection: A retrospective
small-scale study.
AB - H7N9 influenza is a recently emerging infection with a high mortality rate. The
aim of the present study was to investigate dynamic fluctuations of peripheral
blood immune cell subgroups in patients with critical H7N9 infection. Flow
cytometry was used to assess the cells in whole blood samples from 9 cases. With
regard to the innate immune system, in the majority of patients, the natural
killer (NK) cell counts were similar to those of monocytes, which demonstrated a
gradual increase in the progression period and an early increase followed by a
reduction during recovery. B cells exhibited a reduction during progression and
were further decreased during recovery. The CD4+T cells of all patients decreased
during progression, and further decreased during recovery. By contrast, CD8+T
cells increased in the majority of patients in the progression stage, and
underwent an initial reduction followed by a gradual increase during recovery.
However, CD8+ programmed death (PD)-1+T cell and T helper (Th) 1 cell frequencies
demonstrated a moderate increase in all patients during the progression stage,
and regulatory T cell (Treg) frequencies tended to be reduced during progression
and increased during recovery. Notably, this preliminary data also showed that
the frequencies of B cells, Th2 cells and Th17 cells in the progression period
were higher than those in the recovery period. The frequencies of monocytes,
CD4+T cell, CD8+T cell, CD4+PD-1+T cells and CD8+PD-1+T cells in the progression
period were lower than those during recovery. In conclusion, different levels of
peripheral blood immune cell subgroups during the pathogenesis of H7N9 infection
may be associated with elimination of the virus and immune damage.
PMID- 28413499
TI - Identification a nonsense mutation of APC gene in Chinese patients with familial
adenomatous polyposis.
AB - Familial adenomatous polyposis (FAP; Mendelian of Inherintance in Man ID, 175100)
is a rare autosomal dominant disorder characterized by the development of
numerous adenomatous polyps throughout the colon and rectum associated with an
increased risk of colorectal cancer. FAP is at time accompanied with certain
extraintestinal manifestations such as congenital hypertrophy of the retinal
pigment epithelium, dental disorders and desmoid tumors. It is caused by
mutations in the adenomatous polyposis coli (APC) gene. The present study
reported on a Chinese family with FAP. Polymerase chain reaction and direct
sequencing of the full coding sequence of the APC gene were performed to identify
the mutation in this family. A nonsense mutation of the APC gene was identified
in this pedigree. It is a heterozygous G>T substitution at position 2,971 in exon
15 of the APC gene, which formed a premature stop codon at amino acid residue 991
(p.Glu991*). The resulting truncated protein lacked 1,853 amino acids. The
present study expanded the database on APC gene mutations in FAP and enriched the
spectrum of known germline mutations of the APC gene. Prophylactic
proctocolectomy may be considered as a possible treatment for carriers of the
mutation.
PMID- 28413500
TI - Enhancement of humoral and cell mediated immune response to HPV16 L1-derived
peptides subsequent to vaccination with prophylactic bivalent HPV L1 virus-like
particle vaccine in healthy females.
AB - Currently prophylactic HPV16/18 L1 virus-like particle (VLP) vaccines are
employed with great success for the prevention of HPV infection. However, limited
information is available regarding the immune responses against human
papillomavirus (HPV) 16/18 L1 subsequent to HPV16/18 L1 VLP vaccination,
primarily due to the lack of widely used assays for immune monitoring. The aim of
the present study was to identify HPV16 L1-derived B and T cell epitopes for
monitoring the immune responses after HPV16/18 L1 VLP vaccination in healthy
females. The levels of immunoglobulin G (IgG), IgE, IgA and IgM reactive to HPV16
L1-derived peptides were measured by multiplex bead suspension assay. Following
detailed B cell epitope mapping, T cell responses specific to HPV16 L1-derived
peptides were evaluated by an IFN-gamma ELISPOT assay. The levels of IgG, IgM and
IgA reactive to 20-mer peptides (PTPSGSMVTSDAQIFNKPYW) at positions 293-312 and
300-319 of HPV16 L1 were significantly increased in the plasma after 2, 7, and 12
months after first vaccination. Detailed epitope mapping identified the amino
acid sequence (TSDAQIFNKP) at position 301-310 of HPV16 L1 as an immunogenic B
cell epitope. In addition, T cell responses to an HLA-A2- and HLA-A24-restricted
epitope (QIFNKPYWL) at position 305-313 of HPV16 L1 were increased following
immunization, suggesting that the HPV16/18 L1-VLP vaccination as able to induce
specific immune responses in T and B cells simultaneously. The identified B and T
cell epitopes may be useful as a biomarker for monitoring the immune responses
subsequent to HPV16/18 L1 VLP vaccination. Thus, the present study may provide
novel information to improve the understanding of the immune responses to HPV16
L1.
PMID- 28413501
TI - USP39 regulates the growth of SMMC-7721 cells via FoxM1.
AB - The present study investigated ubiquitin specific peptidase 39 (USP39) gene
knockdown on SMMC-7721 cells in vitro and in vivo, and the role of USP39 in
regulating the growth of hepatocellular carcinoma (HCC). Two small interfering
RNAs (siRNA) were constructed, which targeted the USP39 gene and control
sequences were synthesized and inserted into a pGCSIL-GFP lentiviral vector. The
full length of USP39 cDNA was amplified by polymerase chain reaction (PCR) and
cloned into pEGFP-N2, and the recombinant plasmids were transfected into cells.
Knockdown efficiency and upregulation of USP39 was determined by reverse
transcription-quantitative PCR and western blotting. The impact of USP39 on the
growth of SMMC-7721 cells in vitro was examined using an MTT assay, colony
formation, flow cytometry (FCM) and immunohistochemical staining. The impact of
USP39 on the growth of SMMC-7721 cells in vivo was examined by assessing
tumorigenicity in nude mice. Western blotting was performed to examine the
mechanism of USP39 regulation on SMMC-7721 cell growth. Recombinant vectors
containing specific and scrambled USP39 siRNA sequences were constructed and
transfected into SMMC-7721 cells. USP39 knockdown inhibited cell proliferation
and colony formation in SMMC-7721 cells, while upregulation of USP39 promoted the
growth of tumor cells. FCM indicated that USP39 knockdown led to G2/M arrest and
induced apoptosis in SMMC-7721 cells. USP39 knockdown inhibited xenograft tumor
growth in nude mice and led to the downregulation of the transcription factor
Forkhead Box M1 (FoxM1). Gene expression of FoxM1 targets, including polo-like
kinase 1, cyclin B1 and centromere protein A also decreased following USP39
knockdown. The results suggest that knockdown of USP39 inhibits the growth of HCC
in vitro and in vivo, potentially through the induction of G2/M arrest by
regulating the pre-mRNA splicing of FoxM1.
PMID- 28413502
TI - Remifentanil functions in the adaptive protection of cardiac function following
ischemia.
AB - The present study aimed to investigate the effects of remifentanil during
adaptation followinsg myocardial ischemia, and its possible clinical
applications. Remifentanil was used during the simulation of adaptation following
ischemia, which was performed using a Langendorff heart perfusion system. A total
of 75 rats were divided into five groups, and the coronary flow, cardiac output
and the cardiac enzyme content in coronary effluent prior to ischemia and post
reperfusion were recorded. Electron microscopy was used to observe myocardial
ultrastructure, and the volume of aortic and coronary effluent was also measured.
The recovery of cardiac output upon reperfusion was significantly higher
following remifentanil treatment (91%), as compared with the ischemic control
group (78%; P<0.05). The coronary flow of the experimental group following
reperfusion decreased by 4 ml/min compared with the control group not exposed to
ischemia, whilst the coronary flow of the ischemic control group was reduced by
20-24 ml/min. Flameng scoring of the mitochondria demonstrated improved
mitochondrial ultrastructure following remifentanil treatment (score, 1.25+/
0.31), as compared the ischemic control group (score, 3.14+/-0.17). Lactate
dehydrogenase (LDH) levels in the remifentanil-treated group were significantly
lower at 10 and 30 min post-reperfusion (15.3+/-7.1 and 10.2+/-6.8 U/l,
respectively), as compared with the control group (29.7+/-8.3 and 20.6+/-6.8 U/l,
respectively; P<0.05). The results of the present study suggested that the
application of remifentanil following ischemia protected heart function via the
opioid receptors by reducing myocardial enzyme release, and attenuating ischemia
induced changes to the myocardial cell and mitochondrial structure.
PMID- 28413503
TI - Vector-mediated Tum-5 expression in neovascular endothelial cells for treating
hepatocellular carcinoma.
AB - Hypervascular hepatocellular carcinoma (HCC) is one of the leading causes of
cancer-associated mortality. Angiogenesis is an important contributor to HCC
progression and metastasis; therefore, inhibiting angiogenesis may be an
effective method of treating HCC. Tumstatin is a novel type of efficient
endogenous vascular endothelial cell growth inhibiting factor. The anti
angiogenic activity of tumstatin is localized to the 54-132 amino acid region
(Tum-5). In a previous study performed by our group, the gene fragment encoding
Tum-5 was cloned and inserted into a pLXSN retroviral vector. In the present
study, the anti-angiogenic effects of Tum-5 and the antitumor effects exerted by
the pLXSN-Tum-5 vector in vivo were investigated. The results demonstrated that
pLXSN-Tum-5 significantly inhibited the growth of human umbilical vein
endothelial cells compared with pLXSN, but had no obvious effect on HepG2 cell
growth. Moreover, the antitumor and anti-angiogenic activity of Tum-5 was
examined in vivo using a xenograft of H22 HCC cells. The results indicated that
pLXSN-Tum-5 significantly inhibited tumor growth following 5 injections over 10
days. The size and weight of tumors in the pLXSN-Tum-5 group were lower than
those in the saline and pLXSN groups. Furthermore, immunohistochemical analysis
with CD31 antibodies indicated that the average microvessel density in the pLXSN
Tum-5 group were significantly lower than that in the saline and pLXSN groups.
These results suggested that Tum-5 exerts its antitumor activity by suppressing
vascular endothelial cells. The gene fragment of Tum-5 may be developed as an
effective inhibitor of angiogenesis and used to treat patients with HCC.
PMID- 28413504
TI - Early initiation of argatroban therapy in the management of acute superior
mesenteric venous thrombosis.
AB - Acute superior mesenteric venous thrombosis (ASMVT) is an intractable disease
with poor prognosis. Argatroban, a direct thrombin inhibitor, may be a novel
anticoagulant method in the therapy of ASMVT. The aim of the present study was to
assess the efficacy and safety of early argatroban therapy in ASMVT patients. The
current retrospective study reviewed a consecutive series of ASMVT patients
receiving early argatroban therapy during hospitalization between March 2013 and
April 2014, with 18 ASMVT patients included in the study. Of these, 16 patients
without hepatic dysfunction underwent anticoagulant therapy with argatroban with
a mean dose of 1.57+/-0.34 ug/kg/min and a mean duration of 12.2+/-3.7 days,
while their activated partial thromboplastin time (aPTT) was elevated to 1.95+/
0.26 times the baseline value. In addition, 2 hepatic dysfunction patients
received therapy with a dose of 0.41 ug/kg/min and 0.46 ug/kg/min, and with aPTT
of 1.68 and 1.62 times the baseline value, respectively. Overall, 94% (n=17) of
the patients presented clinical improvement, while 88% (n=16) of patients
presented partially or completely dissolved thrombus in contrast-enhanced
computed tomography images. The incidence of surgery and bowel resection was 6%
(excluding 1 case with intestinal necrosis detected on admission). Furthermore,
11% (n=2) of patients experienced a bleeding episode, however no major bleeding
or mortality occurred during hospitalization. During the follow-up, the mortality
and the recurrence rate were 6% and 11%, respectively. In conclusion, early
initiation of argatroban treatment may be an effective and safe therapy in ASMVT,
manifesting efficient resolution of the thrombus, rapid improvement of symptoms,
low incidence of bowel resection and bleeding complication, and low mortality
rate.
PMID- 28413505
TI - Rare scar sarcoidosis: A case report.
AB - A 70-year-old female patient presenting with swelling and subcutaneous nodule
formation localized to the knee scars over a two-month period is presently
reported. Dermatological examinations found erythematous swelling and small
papules on the patient's knee scars, along with subcutaneous nodules beneath and
around the scars. Computer tomography of the chest region identified multiple
obscure tubercles in the lungs and swollen lymph nodes in the hilum pulmonis and
mediastinum. Skin biopsy revealed multiple non-caseating granulomas, which had
infiltrated the dermis. The patient was diagnosed with scar sarcoidosis as a
result of these observations. The onset of scar sarcoidosis is rare and,
therefore, not well understood; however, inflammatory alterations in preexisting
scars may be important indicators for disease onset.
PMID- 28413506
TI - Active efflux pump adeB is involved in multidrug resistance of Acinetobacter
baumannii induced by antibacterial agents.
AB - The aim of the present study was to investigate the resistance of Acinetobacter
baumannii, which was induced by cefepime (FEP), cefoperazone-sulbactam (SCF),
tazobactam (TZP), levofloxacin (LEV), amikacin (AK), imipenem (IPM), and
ciprofloxacin (CIP), in vitro. Multi-step drug resistance selection of 16 A.
baumannii strains was performed using seven antibacterial agents (FEP, TZP, CIP,
AK, IPM, SCF, and LEV). The minimum inhibitory concentration (MIC) was determined
using the agar dilution method. Random amplified polymorphic DNA polymerase chain
reaction was performed to analyze the genotypes and the carrying rates of aac(3)
I, aac(6')-I, ant(3)-I, aph(3)-Via, OXA-23, OXA-24, AmpC, TEM-1, metallo-beta
lactamase gene (IMP), armA, rmtA, rmtB, parC, gyrA and adeB. Expression of adeB
was determined using semi-quantitative reverse transcription-polymerase chain
reaction (Semi-qRT-PCR). Among the 16 strains, 15 strains with drug resistance
(93.8%) were obtained following in vitro induction. Notable increases (8- to 128
fold) were noted in the MIC and different genotypes were showed in RAPD of the
strains before and after performing the drug resistant test. PCR data revealed
significant differences (P<0.05) between the carrying rates of resistant genes
before and after drug induction, with the exception of rmtA, OXA-24, TEM-1, and
IMP. Significant increases were demonstrated in the comparative adeB grayscale in
strains that underwent drug induction when compared with the sensitive strains
(55.69+/-43.11% vs. 10.08+/-26.35%; P=0.001). Findings of the present study
suggest that the active efflux pump, adeB, has an important role in multidrug
resistance of the A. baumannii induced by antibacterial agents in vitro.
PMID- 28413507
TI - Anaphylactic shock caused by haemocoagulase injection in China.
AB - Haemocoagulase injection is a mixture of purified enzymes isolated from the venom
of Bothrops atrox, which is used for the prevention and treatment of haemorrhage.
It is a relatively safe pharmacological agent that does not require a skin test
prior to administration. However, following a literature search, 14 reported
cases of anaphylactic shock caused by haemocoagulase injection were identified,
including one lethal case in China. Using SDS-PAGE and protein identification,
four primary components in haemocoagulase injection were characterized, including
one metalloproteinase, which may be a thromboplastin-like enzyme, and two serine
proteinases, which may be thrombin-like enzymes. Administering concentrated
haemocoagulase injections failed to provoke a positive skin reaction in allergic
patients. Basophil activation tests revealed that haemocoagulase injections did
not upregulate cluster of differentiation 63 or C-C chemokine receptor type 3
expression. These findings suggest that haemocoagulase injection may cause fetal
anaphylaxis. Although it is difficult to determine a clear conclusion without
being able to evaluate the patients that underwent haemocoagulase injection
induced shock, it is unlikely that the venomous components of haemocoagulase
injection cross-react with common allergens in allergic patients. It is possible
that haemocoagulase injection-induced anaphylaxis is caused by its additive
components, such as mannitol and succinylated gelatin.
PMID- 28413508
TI - Comparative evaluation of copeptin and NT-proBNP in patients with severe acute
decompensated heart failure, and prediction of adverse events in a 90-day follow
up period: A prospective clinical observation trial.
AB - The present study compared the prognostic value of a marker, the C-terminal
section of the arginine vasopressin prohormone (copeptin), with N-terminal B-type
natriuretic peptide (NT-proBNP) in patients with severe acute decompensated heart
failure. A prospective, observational cohort study was conducted in a tertiary
care hospital and enrolled 129 patients with severe acute decompensated heart
failure. Clinicians were blinded to investigational markers except NT-proBNP, and
the study participants were followed up for 90 days. The end-point was a
composite of cardiovascular death or re-hospitalization due to decompensated
heart failure. Of the 129 patients enrolled, 47 reached the end-point and 82 were
in a stable condition during follow-up. Receiver operating characteristic curve
analysis revealed that the areas under curve for the prediction of adverse events
within 90 days were similar for copeptin [0.602+/-0.052; 95% confidence interval
(CI), 0.499-0.705], NT-proBNP (0.659+/-0.048; 95% CI, 0.565-0.753) and their
combination (0.670+/-0.050; 95% CI, 0.573-0.767). Kaplan-Meier survival analysis
showed that the predictive value of NT-proBNP regarding the probability of
survival was superior compared with that of copeptin (log-rank test for trend,
P=0.001 vs. 0.040). Furthermore, multivariate Cox proportional-hazards regression
analysis revealed that increased NT-proBNP and copeptin plasma concentrations
were significant independent predictors of adverse events. The present study
provided evidence that copeptin has similar predictive properties compared with
NT-proBNP regarding adverse events within 90-days in patients with severe acute
decompensated heart failure, but that copeptin may not provide superior 90-day
prediction compared to NT-proBNP.
PMID- 28413509
TI - Effects of siRNA-mediated suppression of HPV-11 L1 expression on the
proliferation and apoptosis of vaginal epithelial cells.
AB - The aim of the present study was to investigate the effects of human
papillomavirus (HPV) infection on the gynecological disease of vaginitis and to
demonstrate how the small interfering RNA (siRNA) method may be used for HPV
prevention in the clinic. Human vaginal epithelial cells were transfected with
HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was
transfected with scrambled siRNA. Cell proliferation in each group was analyzed
using the MTT assay and the expression of apoptosis-associated proteins was
measured by western blot analysis. Compared with the control group, HPV-11 L1
mRNA and protein levels were significantly increased following transfection with
the HPV-11 L1 expression vector in cells (P<0.05), but this result was
significantly reversed by silencing of HPV-11 L1 (P<0.05). In addition, cell
proliferation in the HPV-11 group was lower than that in the control group;
however, cell proliferation was significantly increased in cells transfected with
silenced L1 compared with that in the control group (P<0.05). Furthermore,
silencing of HPV-11 L1 significantly decreased caspase-3 and caspase-9
expressions in cells, whereas the expression was increased in the HPV-11 L1 group
(P<0.05). The present study suggested that siRNA-mediated silencing of HPV-11 L1
may have potential therapeutic applications for treating gynecological diseases
associated with HPV-11 infection.
PMID- 28413510
TI - Association of white blood cell counts with left ventricular mass index in
hypertensive patients undergoing anti-hypertensive drug therapy.
AB - Although studies using animal models have demonstrated that nonhemodynamic
factors, including inflammatory cells and cytokines, contribute to left
ventricular hypertrophy (LVH), there is little clinical data to confirm this
association. Therefore in the present study, levels of circulating specific types
of leukocyte were measured to determine the association between white blood cells
and left ventricular mass index (LVMI) in hypertensive patients undergoing anti
hypertensive drug therapy. A total of 144 consecutive hypertensive patients
taking anti-hypertensive drug therapy were enrolled in the current study.
Subjects were divided into two groups: Those with normal geometry and those with
left LVH. Total white blood cells and differentiated subtypes (neutrophils,
lymphocytes, monocytes) were counted, and left ventricular end-diastolic
diameter, left ventricular posterior wall thickness in diastole and inter
ventricular septal wall thickness in diastole were all measured. Analysis
revealed a significant correlation between LVMI and total white blood cell levels
(P=0.013). The percentage of LVH in the highest tertile of WBC was increased
compared with the middle tertile (P=0.008). Furthermore, a significant
correlation between the highest tertile of neutrophil counts and LVH was observed
(P=0.039). However, no significant associations between LVMI and monocyte or
lymphocyte counts were detected. Therefore, the current study determined that
increased total white blood cell and neutrophil subtype counts were associated
with LVMI in hypertensive patients undergoing anti-hypertensive drug therapy.
They may provide convenient and useful markers for further risk appraisal of LVH
caused by nonhemodynamic factors of hypertension.
PMID- 28413511
TI - Application of dead space fraction to titrate optimal positive end-expiratory
pressure in an ARDS swine model.
AB - This study aimed to apply the dead space fraction [ratio of dead space to tidal
volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in
a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models
of ARDS were constructed. A lung recruitment maneuver was then conducted and the
PEEP was set at 20 cm H2O. The PEEP was reduced by 2 cm H2O every 10 min until 0
cm H2O was reached, and VD/VT was measured after each decrement step. VD/VT was
measured using single-breath analysis of CO2, and calculated from arterial CO2
partial pressure (PaCO2) and mixed expired CO2 (PeCO2) using the following
formula: VD/VT = (PaCO2 - PeCO2)/PaCO2. The optimal PEEP was identified by the
lowest VD/VT method. Respiration and hemodynamic parameters were recorded during
the periods of pre-injury and injury, and at 4 and 2 cm H2O below and above the
optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25+/-1.36 cm
H2O. During the Po period, VD/VT decreased to a lower value (0.44+/-0.08)
compared with that during the injury period (0.68+/-0.10) (P<0.05), while the
intrapulmonary shunt fraction reached its lowest value. In addition, a
significant change of dynamic tidal respiratory compliance and oxygenation index
was induced by PEEP titration. These results indicate that minimal VD/VT can be
used for PEEP titration in ARDS.
PMID- 28413512
TI - Long-term statin use before primary percutaneous coronary intervention improves
treatment outcomes of acute myocardial infarction.
AB - Numerous studies have reported that high-dose statin loading therapy prior to
primary percutaneous coronary intervention (PPCI) improves the clinical outcomes
of patients following acute myocardial infarction (AMI). However, little is known
about the effects of long-term statin use prior to PPCI on such outcomes.
Therefore, the aim of the present analysis was to clarify the effects of long
term statin use before PPCI on the treatment outcomes of patients following AMI.
The records of 213 patients who had AMI and met the inclusion criteria were
retrospectively reviewed. Patients were divided into two groups: A control group
(n=178) who had received no statin pretreatment before AMI onset, and a statin
group (n=35) who had received statin treatment for >=1 month before AMI onset.
All patients received a standard treatment regimen for the secondary prevention
of coronary artery disease after PPCI. Baseline clinical variables, details of
the PPCI procedure and clinical outcomes within 3 months after treatment were
reviewed. Patients in the statin group were significantly older than those in the
control group (P=0.003). Compared with the control group, there was a greater
proportion of patients with hyperlipidemia and previous angina pectoris in the
statin group. There were no differences in the use of other drugs (aspirin, beta
blockers and angiotensin-converting enzyme inhibitors) prior to PPCI between the
two groups. The corrected TIMI frame count (cTFC) was significantly lower in the
statin group than in the control group (24.1+/-12.8 vs. 29.4+/-14.3,
respectively; P=0.043). Multivariable linear regression analysis showed that long
term statin use before AMI was a significant predictor of cTFC after PPCI
(P=0.012). Furthermore, the incidence of major adverse cardiac events within 3
months after PPCI was higher in the control group than in the statin group (16.8
vs. 2.9%, respectively; P=0.032). Logistic regression analysis showed that
previous statin use was associated with the incidence of major adverse cardiac
events within 3 months after treatment (P=0.012). The results of the present
study demonstrate that long-term statin use prior to PPCI improved treatment
outcomes after AMI in actual clinical practice.
PMID- 28413513
TI - Huperzine A inhibits immediate addictive behavior but not behavioral
sensitization following repeated morphine administration in rats.
AB - Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to
treat addiction. The current study aimed to examine the effects of huperzine A, a
cholinesterase inhibitor, on behavioral sensitization induced by repeated
morphine administration and relapse induced by contextual conditioning. The
present study also assessed whether the state-dependency hypothesis may explain
the results. Adult rats were divided into four groups (n=8) and intraperitoneally
injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for
5 days. The effect of repeated huperzine A administration alone on locomotor
activity was assessed. For the experiments that analyzed the development of
morphine-induced sensitization, 40 rats were divided into five groups (n=8):
Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine.
Following a withdrawal period of 7 days, all animals were administered saline or
morphine, as appropriate. To test the state-dependency hypothesis, the rats in
the Saline+Morphine group were injected with saline and morphine, while the other
three groups were administered different doses of huperzine A and morphine. To
examine the effect of huperzine A on the expression of morphine-induced
sensitization, the rats in huperzine A+Morphine groups were injected with
appropriate concentrations of huperzine A, and morphine. The current results
indicated that the administration of huperzine A alone did not affect locomotor
activity, while higher doses of huperzine A inhibited the addictive behavior
induced by morphine at the development phase. Additionally, huperzine A
administration during the expression phase of morphine sensitization did not
inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg
huperzine A inhibited the expression of morphine-induced behavioral
sensitization. Therefore, the results of the current study do not support the
state-dependency hypothesis.
PMID- 28413514
TI - Effect of pre-emptive analgesia by continuous femoral nerve block on early
postoperative cognitive function following total knee arthroplasty in elderly
patients.
AB - To the best of our knowledge, the effect of pre-emptively blocking pain
transmission on acute postoperative cognitive dysfunction (POCD) has not yet been
assessed. Therefore, the present study aimed to investigate the effect of pre
emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative
pain and early cognitive function following total knee arthroplasty (TKA) surgery
in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive
analgesia group (n=30) and following TKA surgery in the control group (n=30).
POCD was defined as a two-point reduction in the postoperative score compared
with the preoperative score in the mini-mental state examination. The visual
analog scale (VAS) was used to evaluate the intensity of pain at rest and during
exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia
group was significantly lower than in the control group (P<0.01). In the
preemptive analgesia group, VAS scores at three days post-surgery were lower than
those in the control group (P<0.01). The incidence of POCD on the third
postoperative day was slightly lower in the pre-emptive analgesia group compared
with the control group. In conclusion, the results demonstrate that pre-emptive
analgesia by CFNB may promote the recovery of early cognitive function following
TKA in elderly patients.
PMID- 28413515
TI - Outcome of out-of-hospital cardiac arrest after fibrinolysis with reteplase in
comparison to the return of spontaneous circulation after cardiac arrest score in
a geographic region without emergency coronary intervention.
AB - Coronary occlusion and pulmonary embolism are responsible for the majority of
cases of out-of-hospital cardiac arrest (OHCA). Despite previous favourable
results of pre-hospital fibrinolysis in cases of OHCA, the benefit could not be
confirmed in a large controlled study using the fibrinolytic tenecteplase. For
reteplase (r-PA), there are hardly any data regarding pre-hospital fibrinolysis
during ongoing resuscitation. The present study reported results using r-PA
therapy in a German physician-supported Emergency Medical Services system. The
data of OHCA patients who received pre-hospital fibrinolytic treatment with r-PA
after an individual risk/benefit assessment were retrospectively analysed. To
assess the effectiveness of this approach, the rate of patients with a return of
spontaneous circulation (ROSC) was compared with the corresponding figure that
was calculated with the help of the RACA (ROSC after cardiac arrest) score. The
RACA algorithm predicts the probability of ROSC based on data from the German
Resuscitation Registry. Further outcome data comprised hospital discharge rate
and neurologic status at discharge. From 2001 to 2009, 43 patients (mean age,
58.5 years; 65.1% male; 58.1% ventricular fibrillation) received r-PA. Of these,
20 patients (46.5%) achieved ROSC, compared to a probability of 49.8% according
to the RACA score (P=0.58). A total of 8 patients (18.6%) were discharged alive,
including 5 (11.2%) with a good neurological outcome. For the analysed small
patient collective, pre-hospital r-PA did not offer any benefits with regard to
the ROSC rate. Further analyses of larger patient numbers on a nationwide
registry basis are recommended.
PMID- 28413516
TI - A simple method of placing a coronary sinus catheter through the femoral vein in
miniature swine.
AB - The aim of the present study was to evaluate the feasibility of placing a
coronary sinus (CS) catheter through the femoral veins of miniature swine. A
total of 16 male domestic pigs (3-4 months old, 25+/-2 kg) were used. Firstly,
the anatomic structure of the CS ostium of swine heart was observed at different
angles under X-ray. The guide wire and Cobara catheter were subsequently advanced
into the right atrium through the femoral vein. Subsequently, the guide wire was
retracted behind the fix curve of the Cobara catheter and the catheter bent
spontaneously in the absence of supporting guide wire following retraction. The
catheter was then gently rotated clockwise to direct the catheter tip to the left
allowing the catheter to easily be placed in the CS ostium. This method was
associated with a short procedure time: The time on separation of the blood
vessels was 15.5+/-5.8 min and the time of radiation exposure was 112+/-20 sec.
The success rate of placing the catheter to CS ostium was 100%. Only one pig
experienced a hematoma after the sheath was pulled out. All swine recovered
without serious complications, such as perforation of coronary vein and
pericardial tamponade. Therefore, this method of placing CS catheter is simple,
safe and reliable, which may offer help for related research.
PMID- 28413517
TI - Isoflurane anesthesia induces liver injury by regulating the expression of
insulin-like growth factor 1.
AB - It has been suggested that isoflurane may cause perioperative liver injury.
However, the mechanism of its action remains unknown. The purpose of the present
study was to determine this possible mechanism. Sprague-Dawley rats were randomly
assigned into one of three groups (all n=12): Control group (exposed to mock
anesthesia), isoflurane group (exposed to 2% isoflurane for 90 min), and
isoflurane + insulin-like growth factor 1 (IGF-1) group (exposed to 2% isoflurane
for 90 min and then treated with IGF-1). Reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) and western blotting were conducted to
determine the levels of expression of IGF-1 and its receptor IGF-R. Liver
necrosis was assessed by histological examination. TUNEL assay was performed to
determine the apoptosis of hepatic cells. In addition, the levels of the proteins
caspase-3 and B-cell lymphoma-extra large (Bcl-xL) were measured. Compared with
the control group, levels of IGF-1 and IGF-1R mRNA and protein were significantly
decreased following exposure to isoflurane (all P<0.05). The necrosis rate and
liver apoptosis were significantly increased in the group treated with isoflurane
alone compared with the control group (P<0.05), but were significantly decreased
compared with the isoflurane group following application of IGF-1 (P<0.05).
Additionally, isoflurane exposure significantly increased levels of caspase-3
compared with the control group (P<0.05), but decreased levels of Bcl-xL
(P<0.05). By contrast, application of IGF-1 reversed these changes. The present
study therefore suggests that isoflurane induces liver injury in part by
regulating the expression of IGF-1 and that application of IGF-1 may protect
against liver injury induced by isoflurane exposure.
PMID- 28413518
TI - Effect of N-acetylglucosamine administration on cartilage metabolism and safety
in healthy subjects without symptoms of arthritis: A case report.
AB - N-acetylglucosamine (GlcNAc) is a widely accepted treatment for osteoarthritis
(OA); however, its effect on healthy individuals is poorly understood. To
evaluate the effect of GlcNAc administration on healthy subjects that do not
exhibit symptoms of arthritis, the present randomized, double-blind, placebo
controlled study was performed. In the present study, 68 male and female Japanese
participants, without symptomatic and radiographic evidence of OA, were enrolled
and randomly allocated to receive placebo or GlcNAc (500 or 1,000 mg/day) for 16
weeks. Effects were evaluated using biomarkers for type II collagen degradation
and synthesis, collagen type II cleavage (C2C), procollagen type II carboxy
terminal propeptide (PIICP) and their ratio (C2C/PIICP). Furthermore, safety
assessments were performed via physical parameters, hematology, blood
biochemistry and urinalysis. The results indicated that there was no significant
change in the biomarkers for type II collagen degeneration and synthesis during
and after the intervention with the placebo and two GlcNAc groups. However,
subgroup analysis using subjects with impaired cartilage metabolism (who
exhibited enhanced type II collagen degradation and reduced type II collagen
synthesis) indicated that the C2C levels were significantly decreased at 8
(P<0.05) and 16 (P<0.01) weeks during the intervention in the two GlcNAc (500 mg
and 1,000 mg/day) groups, compared with the placebo group. In contrast, PIICP
levels were not notably different in the placebo and two GlcNAc groups. The
C2C/PIICP ratio was markedly decreased at 12 and 16 weeks during the intervention
in the two GlcNAc groups, compared with the placebo group. Moreover, no
supplement-related adverse events were observed during and after the
intervention. In conclusion, these observations indicate that oral administration
of GlcNAc at doses of 500 and 1,000 mg/day improves cartilage metabolism in
healthy subjects without apparent adverse effects.
PMID- 28413519
TI - AMP-activated protein kinase mediates the effects of lipoprotein-associated
phospholipase A2 on endothelial dysfunction in atherosclerosis.
AB - The present study aimed to investigate the effects of lipoprotein-associated
phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model
of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK)
mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392
patients with coronary artery disease (CAD), including various sub-conditions,
were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In
addition, an in vitro model of atherosclerosis was established by exposing human
umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein
(oxLDL). SB-435495 was used to inhibit Lp-PLA2, and compound C was used to
suppress AMPK expression. Lp-PLA2, AMPKalpha and phosphorylated-AMPKalpha (T172)
expression in HUVECs were evaluated using western blot analysis. The
concentrations of nitric oxide (NO), endothelin 1 (ET-1), intercellular adhesion
molecule 1 (ICAM-1) and platelet/endothelial cell adhesion molecule 1 (PECAM-1)
in cell culture supernatant were determined using commercially available ELISA
kits. MTT assays were employed to indicate changes in cell viability. The current
study found the plasma Lp-PLA2 levels were elevated in the CAD patients with
stable angina pectoris, unstable angina pectoris, acute coronary syndromes and
acute myocardial infarction, compared with a healthy control population. In
addition, the in vitro results showed that Lp-PLA2 expression levels were
elevated in oxLDL-exposed HUVECs. Lp-PLA2 suppression could increase cell
viability, induce the production of NO and decrease the secretion of ET-1, in
addition to suppressing the expression of cell adhesion molecules, including ICAM
1 and PECAM-1 in oxLDL-exposed HUVECs. The expression of AMPKalpha and
phosphorylated-AMPKalpha (T172) was regulated by Lp-PLA2, and AMPK suppression
was able to reverse the effects of Lp-PLA2 with regard to cell viability,
endothelial vasorelaxation capacity and the secretion of adhesion molecules in
oxLDL-exposed HUVECs. In conclusion, the present study provides initial evidence
that Lp-PLA2 is able to cause endothelial dysfunction in an in vitro model of
atherosclerosis, and the effects of Lp-PLA2 on endothelial dysfunction was at
least partially a result of the downregulation of AMPKalpha, thus contributing to
the progression of atherosclerosis.
PMID- 28413520
TI - Prognosis of patients with Acinetobacter baumannii infection in the intensive
care unit: A retrospective analysis.
AB - The present retrospective study aimed to investigate the prognostic factors for
critically ill patients with an Acinetobacter baumannii (A. baumannii) infection.
A total of 37 patients from the intensive care unit (ICU) were enrolled in the
study. Data was collected from patients, including age, gender, ethnicity, A.
baumannii infection status, concurrent infection status, prescribed antibiotics,
Acute Physiology and Chronic Health Evaluation II (APACHE II) and sepsis-related
organ failure assessment (SOFA) scores, procalcitonin level, site of infection,
shock, sepsis and renal replacement therapy status. Univariate and multivariate
analyses were performed to determine the prognostic factors for mortality. In
total, 8 out of the 37 patients included in this trial did not survive, resulting
in an ICU mortality rate of 21.6%. Univariate analysis indicated that, in
comparison with the survival group, APACHE II and SOFA scores were significantly
higher in the mortality group (P<0.002 and P<0.001, respectively). A larger
number of patients with septic shock were detected in the mortality group in
comparison with the survival group (n=4 and n=3, respectively), whereas a larger
number of patients were infected with multidrug-resistant A. baumannii (MDRAB) in
the survival group in comparison with the mortality group (51.9 and 14.3%,
respectively). However, the prognosis was not significantly influenced by
antibiotics administered, mixed infection or the site of infection. Multivariate
analysis demonstrated that the APACHE II score was the only independent factor
affecting the disease prognosis. Receiver operating characteristic curve analysis
of the APACHE II score demonstrated that the area under the curve was 0.845+/
0.078. In patients with an APACHE II score of 15, the sensitivity and specificity
predictions for mortality were 87.5% and 72.4%, respectively. The APACHE II score
at diagnosis was the only independent factor found to assist in the prognosis of
mortality for patients in the ICU with an A. baumannii infection. In conclusion,
the results of the present study demonstrated that the APACHE II score may
contribute towards the prognostic evaluation of patients in the ICU with an A.
baumannii infection.
PMID- 28413521
TI - Efficacy of arsenic trioxide drug-eluting stents in the treatment of coronary
heart disease.
AB - The aim of the current study was to evaluate the safety and clinical efficacy of
arsenic trioxide drug-eluting (AVI) stents, manufactured in China, for the
treatment of coronary heart disease (CHD). Between January and August 2014, 40
patients with CHD admitted to Yongchuan Hospital with implanted AVI stents alone
were selected. A one-year clinical follow-up was completed and one year
postoperative coronary angiography was reviewed. Major adverse cardiovascular
events (MACE), recurrent angina, stent restenosis and stent thrombosis cases were
detected. All 40 patients with CHD completed the one-year clinical follow-up, as
well as the one-year postoperative coronary angiography. The follow-up results
indicated that the MACE rate was 15.0% (6/40), the target lesion
revascularization rate was 15.0% (6/40), the angina recurrence rate was 32.5%
(13/40), the in-stent restenosis rate was 20.0% (8/40) and the stent thrombosis
rate was zero. There were no cases of cardiac death or nonfatal myocardial
infarction. The incidence of restenosis was higher following implantation of the
AVI stent and the safety and clinical efficacy were worse than expected.
PMID- 28413522
TI - Electroacupuncture combined with mosapride alleviates symptoms in diabetic
patients with gastroparesis.
AB - The present study compared the clinical effectiveness of electroacupuncture (EA),
monotherapy and combination therapy involving the administration of EA and
mosapride in diabetic patients with severe or mild symptoms suggestive of
gastroparesis. A total of 56 patients with type 2 diabetes who had symptoms
suggestive of gastroparesis for >3 months were divided into two groups according
to the Gastroparesis Cardinal Symptom Index (GCSI) score, including 33 in the
mild group (GCSI score <3.5) and 23 in the severe group (GCSI score >=3.5).
Initially, all patients received EA monotherapy for 14 days. An effective
response was defined as a reduction of the overall baseline GCSI score by >25%
after treatment. The non-responding patients then received a combination
treatment with EA and mosapride. Gastric emptying was assessed by the 13C
octanoic acid breath test at the beginning and end of each treatment session. Two
patients in the severe group dropped out of the study during the initial
treatment session. The results revealed that 34 early-responding patients (30
from the mild group and 4 from the severe group) treated with EA monotherapy, and
20 non-early-responding patients receiving combination therapy with EA and
mosapride showed clinically significant improvements. Analysis of data from the
mild subgroup demonstrated that EA treatment specifically improved symptoms of
nausea, vomiting, stomach fullness, excessive fullness and bloating. There was no
statistically significant difference in the gastric half-emptying time among
patients prior to and after EA monotherapy. These preliminary results suggested
that EA may be an option for improving mild symptoms in patients with diabetic
gastroparesis, whereas combination therapy involving EA and pharmaceutics is
required in patients with severe symptoms.
PMID- 28413523
TI - Predictors of visual outcome with transsphenoidal excision of pituitary adenomas
having suprasellar extension: A prospective series of 100 cases and brief review
of the literature.
AB - OBJECTIVE: The aim was to assess the factors influencing the visual outcome
following trans-sphenoidal excision of pituitary adenomas. MATERIALS AND METHODS:
One hundred consecutive patients of pituitary adenomas with suprasellar extension
(SSE) were operated by trans-sphenoidal approach from July 2003 to December 2006.
There were 52 male and 48 female patients with a mean age of 42.47 years. The
visual impairment score, which was used to evaluate the visual outcome was
produced by adding the scores for visual acuity and visual field defects of each
patient (from the tables of the German Ophthalmological Society). The mean
diameter, the SSE and the parasellar extension of the lesion were noted in the
magnetic resonance imaging study. The average follow-up was 43.5 months. RESULTS:
The mean diameter of the tumor was 32.97 mm, and the mean SSE was 14.95 mm. The
parasellar extension was present in 27 patients. The vision improved in 61 of the
71 patients (85.91%). The shorter the duration of visual symptoms and smaller the
size of the lesion resulted in better visual outcome. The age and the
preoperative visual impairment did not show any correlation with the visual
outcome. CONCLUSIONS: Patients with visual symptoms of <1-year duration (P <
0.01) and adenomas of <36.5 mm diameter (P < 0.009) have better visual outcome.
PMID- 28413524
TI - Perioperative complications in endovascular neurosurgery: Anesthesiologist's
perspective.
AB - BACKGROUND: Endovascular neurosurgery is known to be associated with potentially
serious perioperative complications that can impact the course and outcome of
anesthesia. We present here our institutional experience in the anesthetic
management of various endovascular neurosurgical procedures and their related
complications over a 10-year period. METHODS: Data was obtained in 240 patients
pertaining to their preoperative status, details of anesthesia and surgery,
perioperative course and surgery-related complications. Information regarding
hemodynamic alterations, temperature variability, fluid-electrolyte imbalance,
coagulation abnormalities and alterations in the anesthesia course was
specifically noted. RESULTS: Among the important complications observed were
aneurysm rupture (2.5%), vasospasm (6.67%), thromboembolism (4.16%), contrast
reactions, hemodynamic alterations, electrolyte abnormalities, hypothermia,
delayed emergence from anesthesia, groin hematomas and early postoperative
mortality (5.14%). CONCLUSION: Awareness of the unique challenges of endovascular
neurosurgery and prompt and appropriate management of the associated
complications by an experienced neuroanesthesiologist is vital to the outcome of
these procedures.
PMID- 28413525
TI - Post ventriculoperitoneal shunt abdominal pseudocyst: Challenges posed in
management.
AB - BACKGROUND: In patients with hydrocephalus, the abdominal cavity has been used
for absorption of cerebrospinal fluid (CSF) since 1905. Ventriculoperitoneal (VP)
shunt operation is followed by abdominal complications in about 5-47% cases.
Abdominal CSF pseudo cyst is an uncommon, but well described complication. AIM:
This survey was conducted to study the clinical profile and management of this
entity. We present our experience with cases of CSF pseudo cyst in children.
MATERIALS AND METHODS: Retrospective analysis of 4 cases diagnosed to have
abdominal pseudo cyst following VP shunt between 2008 and 2013. All the four
cases were suspected clinically and diagnosis was confirmed by abdominal
ultrasonography. RESULTS: In three patients, the cyst was multilocular and of
varying size. Fourth one had a unilocular cyst at the lower end of VP shunt. All
the four patients had features of varying degree raised intracranial pressure and
a two patients had abdominal signs also. All the patients needed open
exploration. Cyst fluid was drained and partial to complete excision of the cyst
was done along with the repositioning of the shunt in abdominal cavity in three
patients and exteriorization of shunt in one patient. Patients were followed for
any further complication over a period of 1-year. CONCLUSION: Abdominal pseudo
cyst is a rare complication after VP Shunt and could result in shunt malfunction
or abdominal symptoms and signs. Whenever suspected it should be confirmed by
imaging, followed by open exploration and repositioning of the shunt.
PMID- 28413526
TI - Neuroendoscopy - Is it safe?
AB - BACKGROUND: The effect of heat in endoscopic instruments used for laparoscopy and
hysteroscopy has been well-studied. Reports of thermal injury from nasal
endoscopes have also been reported. However, there are no experimental studies,
which have objectively documented and provided recommendations for safe use of
endoscopes in neurosurgery. OBJECTIVES: To study the heat generated at the tip of
the endoscope and the subsequent thermal damage caused to a cotton drape placed
in proximity, by varying the intensity of light delivered through different
optical cables, ambient (operating room) temperatures and working distances.
MATERIALS AND METHODS: The study was carried out in the operation theater using a
300 watt xenon light source connected to the endoscope with 3.5 mm and 4.8 mm
optical cables. A digital thermometer was used to record the heat generated at
the tip of the endoscope. RESULTS: The heat generated at the tip of the endoscope
reached its peak in the first 6 min and attained a plateau at 15 min after
turning on a light source of 60% intensity. Thermal injury to the cotton drape
took a longer time with a 3.8 mm cable compared with 4.8 mm cable. The heat
generated at the tip of the endoscope, and thereby the thermal injury caused was
found to be lower when the ambient temperature was close to 20 degrees C.
CONCLUSIONS: Complications related to thermal injuries caused by heat generated
at the tip of an endoscope can be reduced by using a smaller diameter cable,
light intensity of 60%, increasing the working distance (as permissible),
reducing the time spent for dissection while keeping the endoscope very close to
the target and lowering the ambient temperature to 20 degrees C.
PMID- 28413527
TI - First report of important causal relationship between the Adamkiewicz artery
vasospasm and dorsal root ganglion cell degeneration in spinal subarachnoid
hemorrhage: An experimental study using a rabbit model.
AB - BACKGROUND: The blood supply of the lower spinal cord is heavily dependent on the
artery of Adamkiewicz. The goal of this study was to elucidate the effects of
lumbar subarachnoid hemorrhage (SAH) on the lumbar 4 dorsal root ganglion (L4DRG)
cells secondary to Adamkiewicz artery (AKA) vasospasm. MATERIALS AND METHODS:
This study was conducted on 20 rabbits, which were randomly divided into three
groups: Spinal SAH (n = 8), serum saline (SS) (SS; n = 6) and control (n = 6)
groups. Experimental spinal SAH was performed. After 20 days, volume values of
AKA and neuron density of L4DRG were analyzed. RESULTS: The mean alive neuron
density of the L4DRG was 15420 +/- 1240/mm3 and degenerated neuron density was
1045 +/- 260/mm3 in the control group. Whereas, the density of living and
degenerated neurons density were 12930 +/- 1060/mm3 and 1365 +/- 480/mm3 in serum
saline (SS), 9845 +/- 1028/mm3 and 4560 +/- 1340/mm3 in the SAH group. The mean
volume of imaginary AKAs was estimated as 1,250 +/- 0,310 mm3 in the control
group and 1,030 +/- 0,240 mm3 in the SF group and 0,910 +/- 0,170 mm3 in SAH
group. Volume reduction of the AKAs and neuron density L4DRG were significantly
different between the SAH and other two groups (P < 0.05). CONCLUSION: Decreased
volume of the lumen of the artery of Adamkiewicz was observed in animals with SAH
compared with controls. Increased degeneration the L4 dorsal root ganglion in
animals with SAH was also noted. Our findings will aid in the planning of future
experimental studies and determining the clinical relevance on such studies.
PMID- 28413528
TI - Clinical predictors for survival and treatment outcome of high-grade glioma in
Prasat Neurological Institute.
AB - OBJECTIVE: The aim was to identify clinical predictors for survival and examine
treatment outcome in patients with high-grade glioma (HGG). MATERIALS AND
METHODS: The authors retrospectively reviewed medical records of patients who was
diagnosed HGG between January 2007 and December 2009. Demographic data,
radiological data and treatment data of patients were reviewed and analyzed.
RESULTS: A total of 100 patients were analyzed. There was no difference in
demographic data between Grade III and IV glioma. Patients with HGG had median
survival time (MST) 18 months, The MST of patients with Grade III and IV glioma
were 26 and 13 months, respectively. In this study, only anaplastic
oligoastrocytoma and radiotherapy did impact strongly on survival of patients
with HGG. In patients with Grade III and IV glioma, radiotherapy found to have
influence on survival. CONCLUSION: Patients with HGG in Prasat Neurological
Institute had short survival resemble to other previous study. The clinical
predictors for survival of patients were identified on multivariate analysis.
PMID- 28413529
TI - An evaluation of neuroendocrine dysfunction following acute aneurysmal
subarachnoid hemorrhage: A prospective study.
AB - OBJECTIVE: The aim was to investigate the incidence and pattern of neuroendocrine
changes in cases of acute aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND
METHODS: Endocrine assessment was performed in 100 consecutive cases of acute
aneurysmal SAH presenting within 7 days of ictus. The gonadotropic,
somatotrophic, thyrotropic, and corticotrophic axes were evaluated for their
possible dysfunction. RESULTS: A total of 100 cases (38 males, 62 females; age
range - 17-76 years; mean age - 43.6 years) of acute SAH were studied. The
aneurysms were located in the anterior circulation (n = 95) and posterior
circulation (n = 5). The most common hormone deficiency was of growth hormone (n
= 67), followed by gonadotrophin (n = 50), corticotrophin (n = 49) and
thyrotrophin (n = 35). Hyperprolactinemia was noted in 10 cases. One-pituitary
hormone axis deficiency was noted in 26 cases while 67 cases had two or more
pituitary hormone axes dysfunction. A total of 93 cases had hormonal dysfunction
in one or more pituitary hormone axes, and seven cases had no hormonal
dysfunction. CONCLUSIONS: Endocrine dysfunction occurs in 93% cases of acute SAH
and multiple pituitary hormone axes dysfunction occurs in 67% cases. It is
suggested that hormonal evaluation should be considered as part of management of
acute SAH.
PMID- 28413530
TI - Outcome after operative intervention for traumatic brain injuries in the elderly.
AB - INTRODUCTION: The management of traumatic brain injuries in the elderly (age >=
65 years) is a constant dilemma. The aim of this study is to investigate for
factors that may predict outcome of operative treatment in this group of
patients. MATERIALS AND METHODS: A retrospective analysis was conducted on 68
elderly patients who had been operated in a designated center from 2006 to 2010.
Patients' age, Glasgow Coma score (GCS), pupillary responses, imaging findings,
medical conditions, and the use of anticoagulant/antiplatelet agents on patient
outcomes were studied. RESULTS: The overall mortality rate was 55.9%. Older age,
abnormal pupillary response, low GCS, the presence of midline shift and cistern
obliteration on computerized tomography were associated with poor survival.
Patient aged 75-84 with normal bilateral pupillary response still had an overall
survival rate of 52.6% and good outcomes (Glasgow outcome score: 4 or 5) in 36.8%
of patients. Abnormal pupillary response in at least one eye and preoperative GCS
<= 12 were associated with very poor prognosis. CONCLUSIONS: More advanced age
was found to be associated with progressively worse outcome. A subgroup patients
aged below 85 would survive and could achieve good clinical outcome. The
prognosis of those aged over 85 with moderate or severe head injuries was
extremely poor.
PMID- 28413531
TI - Unusual site of Rathke's cleft cyst: A case report and review of literature.
AB - We report an eight years female child of symptomatic giant Rathke's cleft cyst
extending from right parasellar, paraventricular region to right fronto-temporo
parietal cortical surface which is an unusual site for Rathke's cyst. MRI Brain
scans of patient who presented with diminution of vision in right eye with
headache and vomiting revealed a large cystic mass in right parasellar,
paraventricular region with peripheral enhancement and midline shift. In this
case, we performed the right fronto-temporo-parietal craniotomy with drainage and
marsupilization of cyst wall. Histopathologically, it was inflamed Rathke's cleft
cyst with focal epithelial metaplasia.
PMID- 28413532
TI - Spontaneous extradural and subgaleal hematoma: A rare neurosurgical crisis of
sickle cell disease.
AB - Extradural hematoma (EDH) in absence of trauma is a rare entity with only few
cases reported in literature. The various causes reported include: Vascular
malformation of dura, coagulopathies, sinus infection, middle ear or orbital
infection, and tumor. Occurrence of spontaneous EDH as a complication of sickle
cell disease is even much rarer. We report a case with sickle cell disease who
presented with spontaneous extradural and subgaleal hematomas following an
episode of vaso-oclusive crisis. He was managed successfully with surgery. The
association of epidural hematomas in sickling hemoglobinopathies is reviewed. In
all cases, we noticed one episode of sickle cell crisis just before the
occurrence of spontaneous EDH. Perhaps this crisis puts an extra demand over the
hematopoietic skull tissue disrupting inner and outer skull margins leading to
spontaneous EDH and subgaleal hematoma.
PMID- 28413533
TI - Persistent L5 lumbosacral radiculopathy caused by lumbosacral trunk schwannoma.
AB - Schwannomais, usually, benign tumor of nerve sheath that occurs evenly along the
spinal cord. Intra-pelvic schwannoma is very rare entity that may arise from
lumbosacral nerve roots or from sciatic nerve. Radicular pain of the lower limb
as a presenting symptom of pelvic schwannoma is extremely rare. In the current
report, the patient is presented with a right sided L5 radicular pain typical of
lumbar discopathy. Interestingly, a herniated lumbar disc was noted on
lumbosacral magnetic resonance imaging (MRI). In pre-operative studies a large
pelvic mass was detected in the right pre-sacral area with solid and cystic
components consistent with schwannoma. The patient underwent a low midline
laparotomy to evacuate the retroperitoneal mass. Uniquely, we found the tumor to
be arisen from lumbosacral trunk not from a root or peripheral nerve. Most cases
with intra-pelvic schwannoma present so late with vague abdominal and pelvic
discomfort or pain, low back pain, urinary and bowel symptoms because of
compressive effect of the tumor, or incidentally following gynecologic work-ups;
So, these patients are mostly referred to gynecologists and urologists. A
neurosurgeon should have a high degree of suspicion to diagnose such an entity
among his or her patients presented with pains typical for discopathy.
PMID- 28413534
TI - Malignant solitary fibrous tumour of orbit.
AB - Solitary fibrous tumor (SFT) is a rare neoplasm that is thought to be of
mesenchymal origin. Occurrence of such a tumor in the orbit is rare, more so in
its malignant form. Histopathologically, it can mimic several other tumors of the
orbit and can be differentiated by CD34 positivity. We report a case of malignant
transformation of an SFT of the orbit that recurred after 15 years. The
differentiating histopathological features with special stress on the importance
of CD34 positivity and principles of management are outlined. The need for long
term follow-up to detect recurrence and malignancy is stressed.
PMID- 28413535
TI - Third ventricular tuberculoma mimicking as a tumor: Report of a very rare case.
AB - Intracranial tuberculoma is a common neurosurgical problem in developing
countries; however, intraventricular tuberculoma is a rare entity. Here, we
report a rare case of third ventricular tuberculoma in a 21-year-old girl who
presented with features of raised intracranial pressure. Radiological findings
and management of third ventricular tuberculoma would be discussed and literature
regarding such lesions will be reviewed.
PMID- 28413536
TI - Primary cerebellopontine angle glioblastoma in an adult.
AB - Supratentorial glioblastoma is the most frequent primary intracranial tumor in
adults. Its localization in the cerebellum is extremely rare and such tumor
presenting as cerebellopontine angle (CPA) mass in an adult is even rarer. We
report the case of primary cerebellar glioblastoma in a 52-year-old woman who
presented clinically and radiologically as CPA mass. Its clinical presentation,
radiological findings, and treatment instituted are discussed in view of
pertinent literature.
PMID- 28413537
TI - Progressive hemiparesis in a young man: Hemicerebral atrophy as the initial
manifestation of basal ganglia germinoma.
AB - Basal ganglia germinomas are rare and patients are classically young Oriental
males presenting with gradually progressive hemiparesis. Although early treatment
with chemo-radiotherapy can be curative and significantly improve the quality of
life, medical attention is often delayed. A young Chinese male experienced a 6
month history of right hemiparesis with magnetic resonance imaging findings of
hemicerebral atrophy and lentiform nucleus microhemorrhage, highly suggestive and
early signs of basal ganglia germinomas. No further imaging was performed until 2
years later when he was admitted for acute neurological deterioration and a
repeat scan revealed a large infiltrative tumor pathologically confirmed to be a
pure germinoma.
PMID- 28413538
TI - Primary CNS vasculitis masquerading as glioblastoma: A case report and review.
AB - Isolated angitis of the central nervous system (IACNS)/primary angitis of central
nervous system vasculitis (PACNS) is an uncommon vascular disease, sparingly
presenting as an isolated inflammatory lesion on magnetic resonance imaging
(MRI). The disease usually manifests as a long-drawn and progressive ischemic
event. Delay in diagnosis due to focal nature of the lesion also contributes to
the poor prognosis as the dismal natural history and immunosuppressive therapy.
To date, only a few cases with tumor-like isolated angitis of CNS have been
reported with clear and definitive diagnostic workup.
PMID- 28413539
TI - A rare case of congenital glioblastoma with atypical presentation in an eleven
month-old infant: Case report with review of literature.
AB - Glioblastoma multiforme (GBM) is the most common and malignant primary brain
tumor in adults. The occurrence of this entity in infants is a rarity and
portends a uniform dismal prognosis and survival in spite of all the latest
available management options. The authors herein report a case of a GBM in an 11
month-old infant with tumor involving predominantly the left temporal and frontal
regions who expired 10 weeks after tumor decompression. Literature and available
management options have been reviewed in the context of the presented case.
PMID- 28413540
TI - Intraventricular glioblastoma multiforme mimicking meningioma and review of the
literature.
AB - Glioblastoma multiforme (GBM) is the most common primary brain tumor and is
usually found in aged persons in the cerebral hemispheres particularly the
frontotemporal region. But intraventricular GBM is rare and only few cases have
been reported in the literature. We report a case of a 27-year-old man who
presented with headache, vision loss in both eyes, and other signs and symptoms
of increased intracranial pressure. Computed tomography and magnetic resonance
imaging showed an intraventricular, well-circumscribed lesion with homogeneous
enhancement of contrast, suggestive of meningioma that is more common than GBM in
this location. The patient underwent surgical removal through transcortical
route. The final pathologic diagnosis was GBM. We present the clinical features,
radiological findings, and surgical management of this case and discuss the
pathogenesis and review of the literature of intraventricular GBM.
PMID- 28413541
TI - Clival giant cell tumor - A rare case report and review of literature with
respect to current line of management.
AB - Giant-cell tumor (GCT) involving the skull base is rare. Sphenoid bone is the
most commonly involved bone followed by petrous temporal bone. Histopathology and
radiological features of these lesions are similar to GCT involving bone
elsewhere. Unlike other sites, skull base is not an ideal site for the radical
surgery. Hence adjuvant treatment has pivotal role. Radiation therapy with
intensity-modulated radiation therapy, stereotactic radiosurgery or chemotherapy
with adriamycin are promising as described in some case reports. Bisphosphonates
showed good control in local recurrence. In vitro studies with Zolendronate
loaded bone cement and phase 2 trials of Denosumab showed hopeful results, may be
useful in future.
PMID- 28413542
TI - Lateral ventricular gliosarcoma with attachment to septum pellucidum.
AB - Gliosarcomas are lesions with both glial and sarcomatous elements and are usually
seen abutting the dura. Intraventricular location is extremely rare. Such an
unusual intraventricular gliosarcoma is being reported.
PMID- 28413543
TI - Primary intracranial choriocarcinoma presenting as a ring-enhancing lesion: A
case report and review of literature.
AB - We report here a rare case of primary intracranial choriocarcinoma without
evidence of tumor elsewhere, presenting as a ring-enhancing lesion managed
successfully in our institute (Grant Medical College and Sir J. J. Group of
Hospitals, Mumbai, Maharashtra, India). A 22-year-old, right-handed housewife
presented with complaints of headache, vomiting, generalized tonic-clonic
seizures, and right upper limb weakness of short duration. On neurological
examination, the patient was conscious, cooperative, well-oriented in time,
place, and person. Visual acuity was 6/9 in both eyes. Fundus was showing grade 1
papilledema. Tone was increased on the right side. Power was decreased in the
right upper limb as compared to the left. Reflexes were brisk in the right upper
limb. Imaging was suggestive of a thick ring-enhancing lesion in the left
parietal region suggestive of glioma or tuberculosis. Complete excision of the
lesion was achieved. The diagnosis was confirmed by histopathologic examination
of the lesion and beta-human chorionic gonadotropin (beta-HCG) levels. The
patient recovered well postoperatively without neurological deficit. She was
relieved of headache completely and there were no further episodes of vomiting or
seizures. The right upper limb weakness improved to 4+/5. Choriocarcinoma is the
most malignant lesion of all the gestational trophoblastic diseases. Primary
brain choriocarcinoma presenting as a ring-enhancing lesion has not been reported
in the literature. This diagnosis should be kept in mind, especially in young
females of child-bearing age group. Complete surgical excision with adjunctive
treatment is required to achieve prolonged remissions.
PMID- 28413544
TI - Abdominal schwannoma in a case of neurofibromatosis type 2: A report of a rare
combination.
AB - Neurofibromatosis-2 (NF2) is an autosomal-dominant disease, which is
characterized by vestibular schwannomas (VSs) (acoustic neurinoma) as well as
tumours of the peripheral and central nervous system, demonstrating a variety of
expression. A 12-year-old girl presented to us with headache and ataxia for four
months. We examined and found a lump in the right side of her abdomen. On
magnetic resonance imaging (MRI) of brain, a bilateral VS at the cerebellopontine
(CP) angle was detected, and on computerized tomography (CT) scan and
ultrasonography of her abdomen a large retroperitoneal schwannoma was revealed in
the right side of her abdomen. At first, the right-sided CP angle tumour and two
months later, the left-sided lesion was operated. After some days, she became
mute and incontinent, and was found to have hydrocephalus on CT scan. We
introduced a ventriculoperitoneal shunt. Then we operated the abdominal lump,
which was histologically proven as schwannoma. The association of these three
tumours is rare and untiring surgical approaches made her better. The patient
recovered well except bilateral mild facial and vestibulocochlear deficit.
PMID- 28413545
TI - Bilateral cervico-dorsal gossypiboma presenting as discharging sinus.
AB - Retained surgical sponge is an uncommon complication after laminectomy. A 67-year
old male presented with a discharging sinus in the cervical region following
cervical laminectomy. Magnetic resonance imaging (MRI) revealed bilateral
symmetrical lesions in the paraspinal area. Re-exploration revealed gauze pieces
on either side under the muscle. Persistent discharging wound after surgery
should arouse the possibility of a foreign body. Because of the rarity of
bilateral lesions, the present case is being reported.
PMID- 28413546
TI - Solitary plasmacytoma of temporal bone: A rare case report.
AB - Solitary plasmacytoma of base of skull is a rare disease. It presents with
headache, swelling, and other vague symptoms. Systemic work-up to rule out
multiple myeloma is necessary. Radiotherapy is the treatment of choice. We, here,
present a case of solitary plasmacytoma of base of skull in right temporal bone
in a 50-year-old female treated with surgery and radiotherapy.
PMID- 28413547
TI - Supratentorial intermediate grade meningeal melanocytoma with intratumoral bleed
in the background of neurocutaneous melanosis: Report of an unusual case and
review of literature.
AB - Primary melanocytic tumours of the central nervous system (CNS) are rare.
According to the WHO classification (2007), these tumours include diffuse
leptomeningeal melanosis, melanomatosis, melanocytoma, and primary CNS melanoma.
Meningeal melanocytoma, most commonly seen in the infratentorial compartment and
cervical spinal cord, is a benign primary melanocytic neoplasm. Primary CNS
melanoma, on the other hand, represents the malignant end of the spectrum.
Intermediate grade melanocytoma is a rare histological subtype of primary
meningeal tumours and is characterised by the clinicopathological features
between the two extremes. Neurocutaneous melanosis (NCM) is a rare phacomatosis
characterised by melanotic lesions on the skin and leptomeninges. Leptomeningeal
manifestation in NCM may be observed either in the form of diffuse leptomeningeal
melanosis or primary CNS melanoma. Melanocytomas are focal lesions and their
association with NCM is extremely rare. In this report, we present an unusual
case of NCM accompanied by right frontal intermediate grade melanocytoma with
intratumoral bleeding in a 17-year-old boy. A brief literature review is also
presented.
PMID- 28413548
TI - An interesting case of wrongly diagnosed optic neuritis.
AB - Optic neuritis (ON) may rarely mimic optic nerve tumor, index of suspicion should
be kept high. A 34-year-old woman presented to a major academic institute with a
history of right-sided ocular pain and progressive visual loss in the same eye.
Her magnetic resonance imaging showed markedly thickened optic nerve; her workup
for inflammatory pathology was negative; she was diagnosed as a case of optic
nerve tumor and was planned for surgery. Patient for second opinion came to a
tertiary care institute where on proper history taking and evaluation she was
diagnosed and treated on the lines of ON and she improved. The diagnosis of ON is
a clinical one, it may mimic optic nerve tumor in rare cases.
PMID- 28413549
TI - Challenges in a case of ophthalmic artery aneurysm associated with abnormal
internal carotid arteries.
AB - Ophthalmic artery aneurysms account for 5% of all cerebral aneurysms and are an
important cause of morbidity and mortality related to subarachnoid hemorrhage.
The diagnosis is often made only when the aneurysm is large enough to become
symptomatic. They remain technically challenging for both neurosurgeon and
interventional radiologist. We present the case of a 62-year-old woman admitted
for transient loss of consciousness, followed by generalized tonic-clonic
seizures. Computed tomography (CT) showed a subarachnoid hemorrhage (SAH),
clinically graded as Hunt and Hess III. Magnetic resonance imaging (angioMR) and
the four-vessel digital subtraction angiography (DSA) identified a ruptured, 8 mm
left ophthalmic artery aneurysm. Embolization was the first therapeutic choice.
Nevertheless, the attempt had to be aborted due to a combination of a hypoplastic
right internal carotid artery (ICA) and an irregular atheromatous plaque on the
left ICA, rendering the procedure unduly hazardous. Therefore, microsurgical
clipping of the aneurysm became the procedure of choice. Postoperatively, the
patient was in good condition, with no visual and neurological deficits. At 6
months follow up, she was assigned maximum scores of 5 and 8 on the Glasgow
Outcome Scale (GOS) and Extended GOS (GOS-E), respectively. Aneurysm rupture
represents a neurosurgical emergency and an early intervention (less than 48 h)
is recommended to maximize the chances of deficit-free survival. The
peculiarities of this case consisted in the combination between the size and the
location of the aneurysm, abrupt presentation, and the impossibility of
embolization due to bilateral ICA abnormalities, congenital (hypoplastic right
ICA) and acquired (extensively atherosclerotic left ICA).
PMID- 28413550
TI - Primary intracranial rhabdomyosarcoma of the cerebellopontine angle mimicking a
vestibular schwannoma in a child.
AB - Primary intracranial rhabdomyosarcoma (PIRMS) is a rare neoplasm, which affects
infants and young children. We report a rare case of a primary embryonal
rhabdomyosarcoma of the cerebellopontine angle in a 7-year-old boy with clinical
and radiological features mimicking a vestibular schwannoma. The patient
underwent definitive surgery and radiotherapy and is recurrence free at 6 months.
PIRMS commonly occur in parameningeal locations or metastasize to the brain from
an extracranial primary. Gross total tumor resection followed by adjuvant
radiotherapy remains the current standard of treatment; however, chemotherapy has
also been tried with favorable results. The overall prognosis continues to remain
poor.
PMID- 28413551
TI - Alveolar soft part sarcoma with brain metastases.
AB - Metastatic tumors are the most common mass lesions in the brain. This case
reports a rare form of sarcoma with metastasis to the brain. The appropriate
management of a patient with metastatic alveolar soft part sarcoma to the brain
is discussed. Author describes a 32-year-old gentleman diagnosed with primary
tumor at gluteus and distant metastases at lower lobe of right lung and the
brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy
with excision of brain lesion was done. Repeated magnetic resonance imaging of
the brain after 2 months showed rapidly growing new lesions. The next step of
management was made by the oncology team as recurrence rate was high and due to
multi-systemic involvement. Patient was planned for palliative chemotherapy and
to be reassessed later. This case report discusses the appropriate approach to
any form of brain metastases and the role of early follow-up especially after
surgery for better outcome and choice of post operative management such as
radiotherapy or chemotherapy or both for malignant tumors. Based on this report,
it was concluded that every brain tumor patient should be frequently monitored
even in the outpatient setting as most of them are metastatic and rapidly
spreading. The patient should be considered for radiotherapy or chemotherapy or
both after surgery if the histopathology result is suggestive of malignancy.
PMID- 28413552
TI - Trigeminocardiac reflex preceding development of postoperative superior orbital
fissure syndrome.
AB - The superior orbital fissure syndrome (SOFS) is a rare condition presenting as
painful unilateral opthalmoplegia, ptosis, pupillary dilatation and anesthesia of
the upper eyelid and forehead. It has been described after facial trauma. Other
etiologies include infections, tumors or spontaneous hemorrhages in the retro
orbital space. Occurrence of SOFS after surgery in the skull base has not been
described before. We recently encountered a case where a young female developed
SOFS following surgery for cerebrospinal fluid (CSF) rhinorrhea. The occurrence
of SOFS was preceded by episodes of trigemino-cardiac reflex (TCR) during the
surgery. This is the first case report associating TCR with SOFS. We managed the
case report with megadose methylprednisolone and the patient showed improvement
in the deficit over time.
PMID- 28413553
TI - Excision of hypoglossal neurinoma by condyle sparing suboccipital keyhole
approach.
AB - Hypoglossal neurinomas are rare tumors that present with gradually worsening
unilateral wasting of the tongue. The tumors often attain large size prior to
detection and often extend into the hypoglossal canal. Large tumors can distort
the brainstem and cerebellum. Preoperative diagnosis can often be made by
magnetic resonance imaging (MRI) with contrast enhancement. Traditionally,
surgery for these tumors has entailed large transcondylar approaches, often
necessitating occipitocervical stabilization. We managed one 23-year-old female
patient with a large hypoglossal neurinoma. The tumor could be excised completely
by a condyle-sparing minimally invasive suboccipital keyhole approach.
PMID- 28413554
TI - Confounding features of ectopic craniopharyngioma: A differential for tumors
showing diffusion restriction.
AB - Craniopharyngiomas comprise approximately 1-3% of all intracranial tumors and
arise from squamous epithelial rests along remnants of Rathke's cleft. They have
bimodal age distribution. The ectopic sites reported are the nasopharynx,
sphenoid bone, pineal region, cerebellopontine angle and third ventricle. We
report a case of ectopic craniopharyngioma in the Foramen of Monro with
restricted diffusion, which have is an unusual feature, not commonly reported and
is a potential pitfall.
PMID- 28413555
TI - Dissecting intracranial aneurysm in pregnancy: A rare association.
AB - We report a case of dissecting aneurysm of the right posterior cerebral artery
presenting with sudden onset headache and altered behavior during labor. A 26
year-old P1001 with uncomplicated antenatal period, except history of headache
off and on since 32 weeks of pregnancy, developed sudden onset headache and
altered behavior during 3rd stage of labor. She had vaginal delivery and a live
born male baby was delivered with good Apgar score. The CT was suggestive of
subarachnoid hemorrhage and DSA was suggestive of dissecting aneurysm of the
right P2 segment with hypoplasia of right P1 segment and A1 segment of posterior
and anterior cerebral artery, respectively. The patient was managed
conservatively. At 4-month follow-up, the patient was doing well. We discuss
about the rare association of a dissecting aneurysm and pregnancy, especially
dissection of the posterior cerebral artery.
PMID- 28413556
TI - Totally cystic intradural schwannoma in thoracic region.
AB - Spinal schwannomas are benign intradural extramedullary tumors arising from
spinal nerve root sheath. They are usually solid or heterogeneously solid.
Totally cystic schwannomas are rare entities. Herein, we report a 60-year-old
male presenting with backache radiating along the chest wall and weakness of both
lower limbs. He had spastic paraparesis. Magnetic resonance imaging revealed a
cystic mass in the thoracic region. At operation, the cystic mass was seen to be
attached to D4 dorsal rootlets. It was excised in toto and histopathology
confirmed it to be a schwannoma. The relevant literature is reviewed.
PMID- 28413557
TI - C2 Primary leiomyoma in an immunocompetent woman: A case report and review of
literature.
AB - Clinical case report and review of the literature. This is the first case of
primary leiomyoma in an immunocompetent woman without previous history of uterine
leiomyoma being reported in the literature to the best of our knowledge.
Leiomyoma, a type of smooth muscle cell tumor, involving the vertebra is
extremely rare. There were very few primary leiomyoma in patients with AIDS or in
the immune-suppressed patients. This 48-year-old female came with H/o neck pain,
weakness and bladder retention. On examination, tone increased in all four limbs,
power on the right side of the limbs 4/5, power on the left upper limb 0/5, lower
limb 3/5, left plantar was up going, decreased sensation over the left second
cervical vertebra (C2) dermatome and all modalities decreased below C2. X-ray and
magnetic resonance imaging (MRI) of the cervical spine showed kyphosis of the
cervical spine with destruction of the C2 vertebral body along with pathological
fracture. The patient underwent decompression of the C2 lesion through the C2
right pedicle with occipito-C1-C3 lateral mass screws fixation. Lesion anterior
to the cord was reached by a transpedicular approach and decompression was
performed. The lesion was pinkish grey, firm and moderately vascular and was
destroying the C2 vertebral body. The patient improved symptomatically in power
in the left upper limb and lower limb over the next 1 week duration from 0/5 to
4+/5. Histopathology revealed primary leiomyoma. The patient was evaluated with
ultrasound abdomen and contrast tomogram of the chest, abdomen and pelvis to rule
out other possible lesions in the lung, intestines and uterus. We suggest that
leiomyoma should be included in the differential diagnosis of destructive lytic
lesions involving the C2 vertebra. Histopathological examination with
immunohistochemistry is necessary for the definitive diagnosis. Treatment of
choice is surgery with complete removal.
PMID- 28413558
TI - Choroid plexus papilloma.
AB - Choroid plexus tumors are rare intracranial tumors which account for only 0.4
0.6% of all brain tumors. These are intraventricular papillary neoplasms derived
from choroid plexus epithelium and range from choroid plexus papillomas (World
Health Organisation (WHO) grade I) to choroid plexus carcinomas (WHO grade III).
It is an important albeit rare cause of hydrocephalous. We present to you the
case of a 1-year-old child who presented with the signs and symptoms of
hydrocephalous and was diagnosed as choroid plexus papilloma on histopathology.
PMID- 28413559
TI - Intracranial hemorrhage from giant aneurysm in pregnancy: A rare association.
AB - We report a case of giant aneurysm causing subarachnoid hemorrhage in a pregnant
female. A 25-year-old female presented with sudden onset of severe headache and
vomiting with altered sensorium and right hemiplegia. On investigation, she had a
giant supraclinoid segment internal carotid artery (ICA) aneurysm. She was
planned for digital substraction angiography, but during the procedure she
deteriorated neurologically and went into spontaneous labor. The baby was a male
child with weight of 1.1 kg. She was taken up for surgery and aneurysm was
clipped. We discuss the rare occurrence of intracranial hemorrhage in pregnancy
due to a giant ICA aneurysm.
PMID- 28413560
TI - Occipital condyle syndrome as the first sign of skull metastasis from lung
cancer.
PMID- 28413561
TI - Economic and outcome following severe head injury.
PMID- 28413562
TI - Pneumocephalus is not a serious outcome after surgery for chronic SDH.
PMID- 28413563
TI - Severe hypotension in transforaminal lumbar interbody fusion surgery: Is it
vasovagal or?
PMID- 28413564
TI - Extensive traumatic thalamic contusions in a child.
PMID- 28413565
TI - Enrichment of in vivo transcription data from dietary intervention studies with
in vitro data provides improved insight into gene regulation mechanisms in the
intestinal mucosa.
AB - BACKGROUND: Gene expression profiles of intestinal mucosa of chickens and pigs
fed over long-term periods (days/weeks) with a diet rich in rye and a diet
supplemented with zinc, respectively, or of chickens after a one-day amoxicillin
treatment of chickens, were recorded recently. Such dietary interventions are
frequently used to modulate animal performance or therapeutically for monogastric
livestock. In this study, changes in gene expression induced by these three
interventions in cultured "Intestinal Porcine Epithelial Cells" (IPEC-J2)
recorded after a short-term period of 2 and 6 hours, were compared to the in vivo
gene expression profiles in order to evaluate the capability of this in vitro
bioassay in predicting in vivo responses. METHODS: Lists of response genes were
analysed with bioinformatics programs to identify common biological pathways
induced in vivo as well as in vitro. Furthermore, overlapping genes and pathways
were evaluated for possible involvement in the biological processes induced in
vivo by datamining and consulting literature. RESULTS: For all three
interventions, only a limited number of identical genes and a few common
biological processes/pathways were found to be affected by the respective
interventions. However, several enterocyte-specific regulatory and secreted
effector proteins that responded in vitro could be related to processes regulated
in vivo, i.e. processes related to mineral absorption, (epithelial) cell
adherence and tight junction formation for zinc, microtubule and cytoskeleton
integrity for amoxicillin, and cell-cycle progression and mucus production for
rye. CONCLUSIONS: Short-term gene expression responses to dietary interventions
as measured in the in vitro bioassay have a low predictability for long-term
responses as measured in the intestinal mucosa in vivo. The short-term responses
of a set regulatory and effector genes, as measured in this bioassay, however,
provided additional insight into how specific processes in piglets and broilers
may be modulated by "early" signalling molecules produced by enterocytes. The
relevance of this set of regulatory/effector genes and cognate biological
processes for zinc deficiency and supplementation, gluten allergy (rye), and
amoxicillin administration in humans is discussed.
PMID- 28413566
TI - A Hierarchical Predictive Coding Model of Object Recognition in Natural Images.
AB - Predictive coding has been proposed as a model of the hierarchical perceptual
inference process performed in the cortex. However, results demonstrating that
predictive coding is capable of performing the complex inference required to
recognise objects in natural images have not previously been presented. This
article proposes a hierarchical neural network based on predictive coding for
performing visual object recognition. This network is applied to the tasks of
categorising hand-written digits, identifying faces, and locating cars in images
of street scenes. It is shown that image recognition can be performed with
tolerance to position, illumination, size, partial occlusion, and within-category
variation. The current results, therefore, provide the first practical
demonstration that predictive coding (at least the particular implementation of
predictive coding used here; the PC/BC-DIM algorithm) is capable of performing
accurate visual object recognition.
PMID- 28413567
TI - Differential adipokine DNA methylation and gene expression in subcutaneous
adipose tissue from adult offspring of women with diabetes in pregnancy.
AB - BACKGROUND: Offspring of women with diabetes in pregnancy are at increased risk
of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic
mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ,
RETN) play key roles in the pathophysiology of T2DM. We hypothesized that
offspring exposed to maternal diabetes exhibit alterations in epigenetic
regulation of subcutaneous adipose tissue (SAT) adipokine transcription. We
studied adipokine plasma levels, SAT gene expression, and DNA methylation of LEP,
ADIPOQ, and RETN in adult offspring of women with gestational diabetes (O-GDM, N
= 82) or type 1 diabetes (O-T1DM, N = 67) in pregnancy, compared to offspring of
women from the background population (O-BP, N = 57). RESULTS: Compared to O-BP,
we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene
expression of all adipokines in O-GDM, decreased RETN expression in O-T1DM, and
increased LEP and ADIPOQ methylation in O-GDM. In multivariate regression
analysis, O-GDM remained associated with increased ADIPOQ methylation and
decreased ADIPOQ and RETN gene expression and O-T1DM remained associated with
decreased RETN expression after adjustment for potential confounders and
mediators. CONCLUSIONS: In conclusion, offspring of women with diabetes in
pregnancy exhibit increased ADIPOQ DNA methylation and decreased ADIPOQ and RETN
gene expression in SAT. However, altered methylation and expression levels were
not reflected in plasma protein levels, and the functional implications of these
findings remain uncertain.
PMID- 28413568
TI - Triphenylamine-Based Push-Pull Molecule for Photovoltaic Applications: From
Synthesis to Ultrafast Device Photophysics.
AB - Small push-pull molecules attract much attention as prospective donor materials
for organic solar cells (OSCs). By chemical engineering, it is possible to
combine a number of attractive properties such as broad absorption, efficient
charge separation, and vacuum and solution processabilities in a single molecule.
Here we report the synthesis and early time photophysics of such a molecule, TPA
2T-DCV-Me, based on the triphenylamine (TPA) donor core and dicyanovinyl (DCV)
acceptor end group connected by a thiophene bridge. Using time-resolved
photoinduced absorption and photoluminescence, we demonstrate that in blends with
[70]PCBM the molecule works both as an electron donor and hole acceptor, thereby
allowing for two independent channels of charge generation. The charge-generation
process is followed by the recombination of interfacial charge transfer states
that takes place on the subnanosecond time scale as revealed by time-resolved
photoluminescence and nongeminate recombination as follows from the OSC
performance. Our findings demonstrate the potential of TPA-DCV-based molecules as
donor materials for both solution-processed and vacuum-deposited OSCs.
PMID- 28413569
TI - Adsorption and Dissociation of CO2 on Ru(0001).
AB - The adsorption and dissociation of carbon dioxide on a Ru(0001) single crystal
surface was investigated by reflection-absorption infrared spectroscopy (RAIRS)
and temperature-programmed desorption (TPD) spectroscopy for CO2 adsorbed at 85
K. RAIRS spectroscopy shows that the adsorption of CO2 on a Ru(0001) single
crystal is partially dissociative, resulting in CO2 and CO. The CO vibrational
mode was also observed to split into two distinct modes, indicating two general
populations of CO present at the surface. Furthermore, a time-dependent blue
shift is observed, which is characteristic of increasing CO surface coverage. TPD
showed that coverages of up to 0.3 ML were obtained, and no evidence for
chemisorption of oxygen on ruthenium was found.
PMID- 28413570
TI - Role of Adsorbed Water on Charge Carrier Dynamics in Photoexcited TiO2.
AB - Overall photocatalytic water splitting is one of the most sought after processes
for sustainable solar-to-chemical energy conversion. The efficiency of this
process strongly depends on charge carrier recombination and interaction with
surface adsorbates at different time scales. Here, we investigated how hydration
of TiO2 P25 affects dynamics of photogenerated electrons at the millisecond to
minute time scale characteristic for chemical reactions. We used rapid scan
diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS). The decay
of photogenerated electron absorption was substantially slower in the presence of
associated water. For hydrated samples, the charge carrier recombination rates
followed an Arrhenius-type behavior in the temperature range of 273-423 K; these
became temperature-independent when the material was dehydrated at temperatures
above 423 K or cooled below 273 K. A DFT+U analysis revealed that hydrogen
bonding with adsorbed water stabilizes surface-trapped holes at anatase TiO2(101)
facet and lowers the barriers for hole migration. Hence, hole mobility should be
higher in the hydrated material than in the dehydrated system. This demonstrates
that adsorbed associated water can efficiently stabilize photogenerated charge
carriers in nanocrystalline TiO2 and suppress their recombination at the time
scale up to minutes.
PMID- 28413572
TI - Guest Editor Dale Hamilton Provides Expert Guidance for Special Issue on Cardiac
Metabolism.
PMID- 28413573
TI - Journal Announces New Changes for 2017.
PMID- 28413571
TI - Asthma control in primary care: the results of an observational cross-sectional
study in Italy and Spain.
AB - BACKGROUND: Poor asthma control observed in several surveys may be related to a
lack of systematic assessment by physicians and/or to patient underestimation of
symptoms. Along this line, the purpose of this study was to investigate the level
of asthma control in patients attending the GP office for different reasons,
either for renewal of drug prescription or for worsening of asthma symptoms.
METHODS: Each of the 145 General Practitioners (GP) in Italy and Spain selected
at least eight asthmatic patients attending their office for a renewal of drug
prescription (Group A) or for worsening of asthma symptoms (Group B), between May
and December 2009. Asthma Control Test (ACT) and other clinical information
(including SF-12 questionnaire) were collected. RESULTS: Data from 1375 patients
with moderate-severe asthma were analysed (mean age: 47.2 years; female: 59%;
smokers or ex-smokers: 35.4%); 57% were on treatment with ICS-LABA combination.
ACT score < 20 (uncontrolled asthma) was observed in 77.8% Group B patients, as
expected, but also in 28.6% Group A patients. Uncontrolled patients reported
their asthma being well or fairly well controlled in 68.4% of cases. Risk factors
for uncontrolled asthma were older age, asthma severity, and smoking habit. In
uncontrolled patients, GPs changed or increased the level of therapy in 75.8% and
initiated asthma treatment in 61.3% of cases, in association with educational
intervention, closer monitoring or pulmonologist consultations. DISCUSSION: The
systematic use of ACT in asthmatics attending GP's clinic may detect high rates
of uncontrolled patients who underestimate their clinical conditions,
particularly those asking solely for asthma medication renewal. Poor adherence to
daily drug therapy was reported in more than 40% of patients and could be an
important contributor of uncontrolled asthma. CONCLUSIONS: The results highlight
the importance of routine longitudinal assessment of asthma patients in primary
care and point to the need for an increased attention to asthma management by
GPs.
PMID- 28413574
TI - The Failing Heart: Energy Supply, Processing, and Transfer.
PMID- 28413575
TI - The Role of Estrogen in Cardiac Metabolism and Diastolic Function.
AB - Heart failure with preserved ejection fraction (HFpEF) has similar prevalence and
prognosis as HF with reduced EF, but there is no approved treatment for HFpEF.
HFpEF is common in postmenopausal women, which suggests that the absence of
estrogen (E2) plays a role in its pathophysiology. With the country's growing
elderly population, the prevalence of HFpEF is rapidly increasing. This has
triggered a renewed urgency in finding novel approaches to preventing and slowing
the progression of HFpEF. In this review, we address the role of E2 in left
ventricular diastolic function and how it impacts women with HFpEF as well as
animal models. We also discuss the primary potential mechanisms that represent
critical nodes in the mechanistic pathways of HFpEF and how new treatments could
be developed to target those mechanisms.
PMID- 28413576
TI - Timing and Targeting of Treatment in Left Ventricular Hypertrophy.
AB - In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from
persistent cardiac stress. At the molecular level, this results in both transient
and long-term changes to metabolic, sarcomeric, ion handling, and stress
signaling pathways. Although this is initially an adaptive change, the mechanisms
underlying LVH eventually lead to maladaptive changes including fibrosis,
decreased cardiac function, and failure. Understanding the regulators of long
term changes, which are largely driven by transcriptional remodeling, is a
crucial step in identifying novel therapeutic targets for preventing the
downstream negative effects of LVH and treatments that could reverse or prevent
it. The development of effective therapeutics, however, will require a critical
understanding of what to target, how to modify important pathways, and how to
identify the stage of pathology in which a specific treatment should be used.
PMID- 28413577
TI - Circadian Control of Cardiac Metabolism: Physiologic Roles and Pathologic
Implications.
AB - Over the course of the day, the heart is challenged with dramatic fluctuations in
energetic demand and nutrient availability. It is therefore not surprising that
rhythms in cardiac metabolism have been reported at multiple levels, including
the utilization of glucose, fatty acids, and amino acids. Evidence has emerged
suggesting that the cardiomyocyte circadian clock is in large part responsible
for governing cardiac metabolic rhythms. In doing so, the cardiomyocyte clock
temporally partitions ATP generation for increased contractile function during
the active period, promotes nutrient storage at the end of the active period, and
facilitates protein turnover (synthesis and degradation) during the beginning of
the sleep phase. This review highlights the roles of cardiac metabolism rhythms
as well as the potential pathological consequences of their impairment.
PMID- 28413578
TI - Epicardial Fat in the Maintenance of Cardiovascular Health.
AB - Epicardial fat is a unique adipose tissue located between the myocardium and the
visceral layer of pericardium. This tissue is characterized by highly active
fatty acid metabolism and highly expressed thermogenic genes. Epicardial fat and
the underlying myocardium share the same microcirculation, suggesting a close and
strong interaction between these two structures. Under physiological conditions,
epicardial fat protects and supports the heart to exert its normal function. Many
clinical studies have shown significant associations between increased amounts of
epicardial fat and coronary artery disease (CAD). In patients with CAD, increased
epicardial fat becomes inflammatory and may promote plaque development through
secretion of proinflammatory cytokines and other mechanisms. Therefore,
epicardial fat is a biomarker of cardiovascular risk and a potential therapeutic
target for cardiovascular disease. Weight loss and pharmaceuticals can reduce
epicardial fat and improve its protective physiological functions.
PMID- 28413579
TI - Metabolic Recovery of the Failing Heart: Emerging Therapeutic Options.
AB - Heart failure has mortality rates that parallel those of breast cancer. Current
management strategies include neurohormonal blockade, rate control measures,
natriuretic peptide preservation, implantation of mechanical assist devices, and
heart transplantation. Despite these strategies, however, the failing myocardium
remains energy depleted. New strategies to promote metabolic recovery are being
developed to potentially augment current treatment guidelines. For example, an
unexpected finding of our own studies showed that mechanical unloading with
assist devices in advanced-stage heart failure restored metabolic flux.
Unfortunately, at that point it is too late for myocardial recovery. Traditional
metabolic therapies addressing hyperglycemia have had limited long-term outcome
benefit. Now, new therapeutic options are emerging based on increased
understanding of the molecular mechanisms underlying energy depletion. Metabolic
cardiac imaging combined with laboratory diagnostics could guide the design of
individual therapeutic strategies. To date, agents that show benefit in select
individuals include mimetics that stimulate glucagon-like peptide-1, inhibitors
of sodium-glucose cotransporter receptors, drugs that limit fatty acid oxidation,
and hormonal therapy in select individuals. This review will summarize mechanisms
and investigations related to these metabolic approaches to heart failure.
PMID- 28413580
TI - Pet Imaging and its Application in Cardiovascular Diseases.
AB - Cardiovascular diseases (CVDs) are the leading cause of death worldwide and
represent a great challenge for modern research and medicine. Despite advances in
preventing and treating CVD over the decades, there remains an urgent need to
develop sensitive and safe methods for early detection and personalized
treatment. With refinements of molecular imaging technologies such as positron
emission tomography (PET), noninvasive imaging of CVDs is experiencing impressive
progress in both preclinical and clinical settings. In this review, we summarize
advances in cardiovascular PET imaging, highlight the latest development of CVD
imaging probes, and illustrate the potential for individualized therapy based on
metabolic phenotype.
PMID- 28413583
TI - Cardiac Metastases in a Patient with Advanced Squamous Cell Carcinoma of the
Lung.
PMID- 28413581
TI - Robotic-Assisted Inferior Vena Cava Filter Retrieval.
AB - Although anticoagulation remains the mainstay of therapy for patients with venous
thromboembolism, guidelines recommend the use of inferior vena cava (IVC) filters
in those who fail anticoagulation or have contraindications to its use. Short
term use of filters has proven effective in reducing the rate of pulmonary
embolism. However, their extended use is associated with a variety of
complications such as thrombosis, filter migration, or caval perforation, thus
making a case for timely filter retrieval. This is the case of a 68-year-old
female with a history of chronic oral anticoagulation use for multiple deep
venous thrombi (DVT) and pulmonary emboli (PE) who required cervical and thoracic
spinal intervention for spondylosis and foramina stenosis. Given her increased
risk of recurrent DVT and PE perioperatively, we elected to place a Cook CelectTM
IVC filter (Cook Medical, Bloomington, IN) after oral anticoagulation was stopped
for the procedure. Her treatment course was prolonged due to wound-healing
complications. We elected to use the Magellan Robotic Catheter System (Hansen
Medical, Mountain View, CA) for filter retrieval when she presented 6 months
later with caval perforation from the filter struts. With its ease of use,
superior mechanical stability, and maneuverability, robot-assisted IVC filter
retrieval may be a safer and more reliable substitute for traditional navigation
techniques when presented with challenging filter retrievals.
PMID- 28413582
TI - A Case of Iatrogenic Aortic Intramural Hematoma.
AB - Iatrogenic aortic dissection during percutaneous coronary intervention is a rare
but serious complication. Both conservative and surgical approaches have been
proposed as management strategies. We describe a case of an 87-year-old female
who presented with an acute coronary syndrome complicated by the development of
an ascending aortic dissection during percutaneous intervention, and we provide a
brief review of the literature.
PMID- 28413585
TI - Pied Beauty.
PMID- 28413584
TI - Hyponatremia in Heart Failure.
PMID- 28413587
TI - Arctic Blimp and Sub on Ray.
PMID- 28413586
TI - The Methodist DeBakey Heart & Vascular Center a Poetic History (Abridged).
PMID- 28413588
TI - Relative biocompatibility of micro-hybrid and nano-hybrid light-activated
composite resins.
AB - Background. In vitro studies have revealed a direct association between resin
content and cytotoxicity of composite resins; however, implantation studies in
this regard are sparse. This study investigates the relationship between filler
content of composite resins and biocompatibility. Methods. This research employed
twelve 180-200-gr male Wistar rats, 1 nano-hybrid (Prime-Dent Inc.) and 1 micro
hybrid (Medental Inc.) composite resins containing 74% and 80-90% filler content,
respectively. The samples were assessed on the 2nd, 14th and 90th day of
implantation. Four rats were allocated to each day in this experimental study. A
section of 1.5mm long cured nano-hybrid and micro-hybrid materials were implanted
into the right and left upper and lower limbs of the rats, respectively. Eight
samples were generated on each day of observation. Inflammation was graded
according to the criteria suggested by Orstavik and Major. Pearson's chi-squared
test was employed to determine the relationship between the tissue responses of
the two materials. Statistical significance was set at P < 0.05. Results . The
average grade of inflammation for the nano-hybrid on the 2nd day of implantation
was 3.3. The micro-hybrid resin had a score of 3.0 for cellular inflammation. On
the 14th day, the micro-hybrid resin also exhibited a lower average grade for
cellular inflammation. On the 90th day, the micro-hybrid resin had a higher grade
of inflammation (0.9) compared to 0.3 recorded for nano-hybrid. The composite
resins with higher filler content elicited a significantly lower grade of
inflammation irrespective of the duration (chi=20.000, df=8, P=0.010) while the
composite resins with lower filler content elicited a significantly lower
inflammatory response on the 90th day (chi=4.000, df=1, P=0.046). Conclusion. The
composite resins with higher filler content generally elicited significantly
lower grades of inflammation, and the composite resins with lower filler content
exhibited significantly lower inflammatory response on the 90th day of
implantation.
PMID- 28413589
TI - The color masking ability of a zirconia ceramic on the substrates with different
values.
AB - Background. The color masking ability of a restoration plays a significant role
in coveringa discolored substructure; however, this optical property of zirconia
ceramics has not been clearly determined yet. The aim of this in vitro study was
to evaluate the color masking ability of a zirconia ceramic on substrates with
different values. Methods. Ten zirconia disk specimens,0.5 mm in thickness and 10
mm in diameter, were fabricated by a CAD/CAM system. Four substrates with
different values were prepared, including: white (control), light grey, dark
grey, and black. The disk specimens were placed over the substratesfor
spectrophotometric measurements. A spectrophotometer measured the L*, a*, and b*
color attributes of the specimens. Additionally, DeltaE values were calculated to
determine the color differences between each group and the control,and were then
compared with the perceptional threshold of DeltaE=2.6. Repeated-measures ANOVA,
Bonferroni, and one-sample t-test were used to analyze data. All the tests were
carried out at 0.05 level of significance. Results. The means and standard
deviations of DeltaE values for the three groups of light grey, dark grey and
black were 9.94+/-2.11, 10.40+/-2.09, and 13.34+/-1.77 units,
respectively.Significant differences were detected between the groups in the
DeltaE values (P<0.0001).The DeltaE values in all the groups were more than the
predetermined perceptional threshold(DeltaE>2.6) (P<0.0001). Conclusion. Within
the limitations of this study, it was concluded that the tested zirconia ceramic
did not exhibit sufficient color masking ability to hide the grey and black
substrates.
PMID- 28413590
TI - Effect of nano-hydroxyapatite toothpaste on microhardness ofartificial carious
lesions created on extracted teeth.
AB - Background. Many types of toothpastes contain substances that can remineralize
initial enamel caries. This study aimed to assess the effect of nano
hydroxyapatite (NHA) on microhardness of artificially created carious lesions.
Methods. In this in vitro study, NHA was prepared using sol-gel technique and
added to the toothpaste with 7% concentration. A total of 80 extracted sound
teeth were collected. The crowns were polished using 500-grit abrasive paper. The
specimens were randomly coded from 1 to 80. Number 1 to 40 were assigned to group
A and numbers 41 to 80 to group B. The microhardness was measured using HVS-1000
Vickers microhardness tester. The specimens were demineralized using 37%
phosphoric acid for 3 minutes in order to create artificial carious lesions and
then were rinsed with water, air-sprayed for 3 minutes and dried. Microhardness
was measured again. Next, the specimens were brushed for 15 days, twice daily,
for 15 seconds. After 15 days, microhardness was measured again. Toothpaste A
contained NHA and fluoride and toothpaste B contained fluoride alone. Data were
analyzed using SPSS 16, with one-sample Kolmogorov-Smirnov test and ANOVA at a
significance level of P<0.05. Results. The microhardness of specimens
significantly decreased following acid exposure (P<0.01) but increased again in
both groups after exposure to toothpastes. The increase in microhardness was
significantly greater in group A (P<0.01). Conclusion. The toothpaste containing
NHA was more effective than the toothpaste without NHA for the purpose of
remineralization.
PMID- 28413591
TI - Comparative evaluation of efficacy of subgingivally delivered 1.2% Atorvastatin
and 1.2% Simvastatin in the treatment of intrabony defects in chronic
periodontitis: a randomized controlled trial.
AB - Background. Statins are the recently evolved agents that aid in periodontal
regeneration and ultimately in attaining periodontal health. Atorvastatin (ATV)
and Simvastatin (SMV) are specific competitive inhibitors of 3-hydroxy-2-methyl
glutaryl coenzyme A reductase. The current study was conducted to compare the
effectiveness of 1.2% ATV and 1.2% SMV, in addition to scaling and root planing
(SRP), in the treatment of intrabony defects in subjects with chronic
periodontitis. Methods. Ninety-six individuals were categorized into three
treatment groups: SRP plus 1.2% ATV, SRP plus 1.2% SMV and SRP plus placebo.
Clinical parameters of full-mouth plaque index (PI), modified sulcus bleeding
index (mSBI), probing depth (PD), and relative attachment level (RAL) were
recorded at baseline before SRP and at 3, 6 and 9 months. Bone fill was assessed
using percentage radiographic defect depth reduction at baseline, 6 months and 9
months. Results. Both ATV and SMV showed significant PD reduction and RAL gain
than placebo. ATV group showed greater mean PD reduction and mean RAL gain as
compared to SMV group at 3, 6 and 9 months. Furthermore, ATV group sites
exhibited a significantly greater percentage of radiographic defect depth
reduction (33.23 +/- 3.11%; 34.84 +/- 3.07%) as compared to SMV (30.39 +/- 3.36%;
32.15 +/- 3.37%) at 6 and 9 months. Conclusion. ATV resulted in greater
improvements in clinical parameters with higher percentage of radiographic defect
depth reduction as compared to SMV in the treatment of intrabony defects in CP
subjects.
PMID- 28413592
TI - Marginal bone loss around platform-switched and non-platform switched implants
after two years of placement: a clinical trial.
AB - Background. The present study was conducted to investigate the marginal bone loss
around two different types of implant-abutment junctions, called platform
switched (Implantium system) and non-platform switched (XiVE system) after two
years of loading. Methods. Sixty-four implants in 49 patients were included in
the study. The implants were placed in the posterior mandibular region according
to the relevant protocols. The extent of bone loss around the implants was
measured and compared after 24 months, using digital parallel periapical
radiographs. Results. The means +/- SE of bone loss values in the platform
switched and non-platform-switched groups were 0.47 +/- 0.048 mm and 1.87 +/-
0.124 mm, respectively. The difference between the two groups was statistically
significant (P < 0.0001). Conclusion . The platform-switching technique seems to
reduce the periimplant crestal bone resorption, which supports the long-term
predictability of implant therapy.
PMID- 28413593
TI - Comparison of bracket bond strength to etched and unetched enamel under dry and
wet conditions using Fuji Ortho LC glass-ionomer.
AB - Background. Acid etching prior to orthodontic bracket bonding may result in
enamel wear or cracks following bracket removal. The manufacturer of Fuji Ortho
LC glass-ionomer (GI) claims that it can bond brackets to wet unetched enamel.
This study aimed to compare the bracket bond strength to etched and unetched
enamel under dry and wet conditions. Methods. In this in vitro study, 60 intact
premolar teeth were randomly assigned to 6 groups (etched and dried, etched and
moistened with distilled water, etched and moistened with saliva, unetched and
dried, unetched and moistened with water, unetched and moistened with saliva). In
all the groups, Leon 4 brackets were bonded to the enamel using Fuji Ortho LC GI.
The teeth were immersed in distilled water at 37 degrees C for 24 hours and
subjected to shear loads at a crosshead speed of 5 mm/min in a Zwick machine for
bond strength testing. Data were analyzed with ANOVA, Tukey test and independent
t-test. Results . The mean bond strength values in groups 1 (etched, dry), 2
(etched, moistened with water), 3 (etched, moistened with saliva), 4 (unetched,
dry), 5 (unetched, moistened with water) and 6 (unetched, moistened with saliva)
were 21.86, 16.46, 10.49, 8.12, 9.15 and 9.52 MPa, respectively. Significant
differences in bond strength were detected between groups 1 and 2 and all the
other groups (P < 0.05), with no significant difference between groups 1 and 2 (P
> 0.05). Conclusion. Fuji Ortho LC GI provided adequate bond strength between
brackets and enamel. To acquire higher bond strength, brackets must be bonded to
etched and dried enamel.
PMID- 28413595
TI - Effect of retreatment on the push-out bond strength of MTA-based and epoxy resin
based endodontic sealers.
AB - Background. Further studies on the adhesion properties of MTA-based materials
seem necessary due to their growing use in endodontic treatment. This research
aimed to assess the effect of retreatment on the bond strength of MTA-based (MTA
Fillapex) and epoxy resin-based (AH Plus) sealers. Methods. ProTaper rotary files
were applied to prepare the root canals of 80 human mandibular premolars. Then,
the roots were randomly divided intotwo groups of A (n=40) and B (n=40), which
were obturated with gutta-percha and MTA Filla-pex and AH Plus sealer,
respectively. In both groups, the teeth were randomly subdivided into 2
subgroups. No retreatment was carried out in subgroups A1 and B1, while subgroups
A2 and B2 were retreated with rotary files and a solvent. Then, a push-out test
was performed on four 2-mm slices of each tooth at a distance of 2 mm from the
coronal surface after two weeks of incubation. Data were analyzed with two-way
ANOVA and statistical significance was set at P<0.05. Results. Regardless of the
procedure followed (P<0.001), significant differences were detected in the mean
bond strength values between the two sealers. Irrespective of the sealer type
(P=0.3), no significant differences were revealed by comparing the mean bond
strength values of the study subgroups. Furthermore, no statistically significant
interaction (P=0.5) was found between the treatment and sealer types. Conclusion.
AH Plus sealer exhibited a higher bond strength compared to MTA Fillapex.
Retreatment using rotary files and chloroform had no statistically significant
effect on the bond strength of sealers evaluated in this study.
PMID- 28413594
TI - The effect of repeated preheating of dimethacrylate and silorane-based composite
resins on marginal gap of class V restorations.
AB - Background. One of the problems with composite resin restorations is gap
formation at resin-tooth interface. The present study evaluated the effect of
preheating cycles of silorane- and dimethacrylate-based composite resins on gap
formation at the gingival margins of Class V restorations. Methods. In this in
vitro study, standard Class V cavities were prepared on the buccal surfaces of 48
bovine incisors. For restorative procedure, the samples were randomly divided
into 2 groups based on the type of composite resin (group 1: di-methacrylate
composite [Filtek Z250]; group 2: silorane composite [Filtek P90]) and each group
was randomly divided into 2 subgroups based on the composite temperature (A: room
temperature; B: after 40 preheating cycles up to 55 degrees C). Marginal gaps
were measured using a stereomicroscope at *40 and analyzed with two-way ANOVA.
Inter- and intra-group comparisons were analyzed with post-hoc Tukey tests.
Significance level was defined at P < 0.05. Results. The maximum and minimum gaps
were detected in groups 1-A and 2-B, respectively. The effects of composite resin
type, preheating and interactive effect of these variables on gap formation were
significant (P<0.001). Post-hoc Tukey tests showed greater gap in dimethacrylate
compared to silorane composite resins (P< 0.001). In each group, gap values were
greater in composite resins at room temperature compared to composite resins
after 40 preheating cycles (P<0.001). Conclusion. Gap formation at the gingival
margins of Class V cavities decreased due to preheating of both composite re
sins. Preheating of silorane-based composites can result in the best marginal
adaptation.
PMID- 28413596
TI - Non-syndromic multiple supernumerary premolars: Clinicoradiographic report of
five cases.
AB - Hyperdontia or supernumerary teeth in both arches without any syndromic
manifestation are extremely rare. Supernumerary teeth are commonly associated
with Gardner's syndrome, cleft lip and palate, cleidocranial dysplasia and
trichorhinopha-langeal syndrome. Five cases of non-syndromic multiple premolars
of maxillary and mandibular arches in Indian patients are presented here. This
case series reports three cases with multiple (9 in maximum), bilaterally
impacted and erupted supernumerary teeth and two cases with supernumerary
premolars in non-syndromic cases from Indian patients. Supernumerary teeth can be
present in any region of the oral cavity. Although the occurrence of maxillary
para-premolars is rare, radio-logical investigations play a major and decisive
role in determining the management of such cases.
PMID- 28413597
TI - Concurrent manifestation of clinical hypodontia and blindness: a case report.
AB - A case is reported of a 26-year-old blind man with hypodontia and multiple
apparently underdeveloped impacted teeth. The patient reported that he had
progressively developed visual impairment at the age of 11 years whence he became
totally blind when he turned 12 years. The aim of this report is to open an
academic and professional debate on the challenges of its definitive diagnosis
and appropriate intervention.Blindness is not reported in any of the previously
described syndromes; therefore, concurrent manifestation of "hypodontia,
blindness, failure of eruption and digital lesions" can be proposed as a
syndrome. However, in the absence of genetic studies, it is difficult to
characterize this case with any one of the specifically documented syndromes;
therefore, academic and professional discourse is suggested with regard to
appropriate intervention.
PMID- 28413598
TI - Solitary peripheral ivory osteoma of the mandible presenting with difficulty in
deglutition: a case report.
AB - Osteomas are benign bone tumors which arise from the cortex or medulla of
craniofacial and jaw bones. They are usually asymptomatic or present as slow
growing painless masses. Larger lesions may present with aesthetic (facial
asymmetry) and functional disturbances (jaw deviation, difficulty in breathing,
pain, and sensory deficits). This paper highlights a case of solitary peripheral
osteoma composed of a compact bony mass arising from the lower border of the
mandible in an adult female patient. The lesion presented with discomfort during
deglutition, which was attributed to impingement of muscles of the oral cavity
floor, including the anterior belly of digastric muscle.
PMID- 28413599
TI - Rare features associated with Mobius syndrome: Report of two cases.
AB - Mobius syndrome is a rare congenital disorder with the preliminary diagnostic
criteria of congenital facial and abducent nerve palsy. Involvement of other
cranial nerves, too, is common. Prevalence rate of this syndrome is approximately
1 in 100,000 neonates. It is of unknown etiology with sporadic occurrence.
However, data regarding the occurrence rate in India is limited. Features such as
orofacial malformations, limb defects, and musculoskeletal, behavioral, and
cognitive abnormalities might be associated. A thorough evaluation to identify
the condition and establishing an adequate treatment plan is of utmost important
in this condition. We are reporting clinical and radiographic features of Mobius
syndrome in two cases along with unusual findings of limb and neck deformity.
PMID- 28413600
TI - Screening the use of informed consent forms prior to procedures involving
operative dentistry: ethical aspects.
AB - Background. The present study aimed to screen the knowledge and attitudes of
dentists toward the use of informed consent forms prior to procedures involving
operative dentistry. Methods. A research tool containing questions
(questionnaire) regarding the use of informed consent forms was developed. The
questionnaire consisted of seven questions structured to screen the current
practice in operative dentistry towards the use of informed consent forms.
Results. The questionnaires were distributed among 731 dentists, of which 179
returned them with answers. Sixty-seven dentists reported not using informed
consent forms. The main reasons for not using informed consent forms were: having
a complete dental record signed by the patient (67.2%) and having a good relation
with patients (43.6%). The dentists who reported using informed consent forms
revealed that they obtained them from other dentists and made their own
modifications (35.9%). Few dentists revealed contacting lawyers (1.7%) and
experts in legal dentistry (0.9%) for the development of their informed consent
forms. Conclusion. A high number of dentists working in the field of operative
dentistry behave according to the ethical standards in the clinical practice,
becoming unprotected against ethical and legal actions.
PMID- 28413601
TI - A few of my favorite things: circumscribed interests in autism are not
accompanied by increased attentional salience on a personalized selective
attention task.
AB - BACKGROUND: Autistic individuals commonly show circumscribed or "special"
interests: areas of obsessive interest in a specific category. The present study
investigated what impact these interests have on attention, an aspect of autistic
cognition often reported as altered. In neurotypical individuals, interest and
expertise have been shown to result in an automatic attentional priority for
related items. Here, we examine whether this change in salience is also seen in
autism. METHODS: Adolescents and young adults with and without autism performed a
personalized selective attention task assessing the level of attentional priority
afforded to images related to the participant's specific interests. In addition,
participants performed a similar task with generic images in order to isolate any
effects of interest and expertise. Crucially, all autistic and non-autistic
individuals recruited for this study held a strong passion or interest. As such,
any differences in attention could not be solely attributed to differing
prevalence of interests in the two groups. In both tasks, participants were asked
to perform a central target-detection task while ignoring irrelevant distractors
(related or unrelated to their interests). The level of distractor interference
under various task conditions was taken as an indication of attentional priority.
RESULTS: Neurotypical individuals showed the predicted attentional priority for
the circumscribed interest images but not generic items, reflecting the impact of
their interest and expertise. Contrary to predictions, autistic individuals did
not show this priority: processing the interest-related stimuli only when task
demands were low. Attention to images unrelated to circumscribed interests was
equivalent in the two groups. CONCLUSIONS: These results suggest that despite
autistic individuals holding an intense interest in a particular class of
stimuli, there may be a reduced impact of this prior experience and expertise on
attentional processing. The implications of this absence of automatic priority
are discussed in terms of the behaviors associated with the condition.
PMID- 28413603
TI - Hepatitis B virus promotes cancer cell migration by downregulating miR-340-5p
expression to induce STAT3 overexpression.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer
related deaths worldwide, and infection with hepatitis B virus (HBV) is a leading
cause of HCC. Previous studies have demonstrated that expression of the tumor
inhibitor miR-340 is significantly downregulated in HCC tissues compared with
normal liver tissues. However, the precise biological role of miR-340-5p in HBV
HCC and its molecular mechanism of action remain unknown. RESULTS: Expression of
miR-340-5p was downregulated in HBV-associated HCC liver tissue and HBV-infected
cells, facilitating migration of liver cancer cells. Signal transducer and
activator of transcription (STAT)3 was found to be a direct functional target of
miR-340-5p. The regulation of STAT3 expression by miR-340-5p was assessed using
qRT-PCR and western blotting, and the effects of exogenous miR-340-5p and STAT3
on the migration of HBV-infected cells were evaluated in vitro using Transwell(r)
and wound-healing assays. The expression of E-cadherin and vimentin, associated
with epithelial-mesenchymal transition, was also assessed using Western blotting
after transfection of miR-340-5p mimics and/or STAT3 expression vectors.
Overexpression of STAT3 resulted in rescue of HBV effects, decreased E-cadherin
expression, increased vimentin expression, and ultimately, enhanced cell
migration. Re-introduction of the STAT3 CDS led to marked reversal of the
inhibition of cell migration in HBV-infected cells mediated by miR-340-5p.
CONCLUSIONS: Hepatitis B virus promotes the migration of liver cancer cells by
downregulating miR-340-5p expression to induce STAT3 overexpression. Our results
show that STAT3 plays a key role in regulating cell migration in HBV-HCC
involving miR-340-5p.
PMID- 28413602
TI - Do sex differences in CEOAEs and 2D:4D ratios reflect androgen exposure? A study
in women with complete androgen insensitivity syndrome.
AB - BACKGROUND: Studies investigating the influence of perinatal hormone exposure on
sexually differentiated traits would greatly benefit from biomarkers of these
early hormone actions. Click-evoked otoacoustic emissions show sex differences
that are thought to reflect differences in early androgen exposure. Women with
complete androgen insensitivity syndrome (CAIS), who lack androgen action in the
presence of XY-chromosomes, enabled us to study the effect of complete androgen
inaction. The main goal was to investigate a possible link between click-evoked
otoacoustic emissions and effective androgen exposure and, thus, whether this can
be used as a biomarker. In addition, we aimed to replicate the only previous 2nd
vs 4th digit-ratio study in women with CAIS, because despite the widely expressed
criticisms of the validity of this measure as a biomarker for prenatal androgen
exposure, it still is used for this purpose. METHODS: Click-evoked otoacoustic
emissions and digit ratios from women with CAIS were compared to those from
control men and women. RESULTS: The typical sex differences in click-evoked
otoacoustic emissions and digit ratios were replicated in the control groups.
Women with CAIS showed a tendency towards feminine, i.e., larger, click-evoked
otoacoustic emission amplitudes in the right ear, and a significant female
typical, i.e., larger, digit ratio in the right hand. Although these results are
consistent with androgen-dependent development of male-typical click-evoked
otoacoustic emission amplitude and 2nd to 4th digit ratios, the within-group
variability of these two measures was not reduced in women with CAIS compared
with control women. CONCLUSIONS: In line with previous studies, our findings in
CAIS women suggest that additional, non-androgenic, factors mediate male-typical
sexual differentiation of digit ratios and click-evoked otoacoustic emissions.
Consequently, use of these measures in adults as retrospective markers of early
androgen exposure is not recommended.
PMID- 28413604
TI - The role of GLI1 for 5-Fu resistance in colorectal cancer.
AB - Colorectal cancer is a leading cause of cancer-related mortality worldwide, with
Fluorouracil (5-FU)-based chemotherapy as the major treatment for advanced
disease. Many patients with advanced colorectal cancer eventually succumb to the
disease despite some patients responded initially to chemotherapy. Thus,
identifying molecular mechanisms responsible for chemotherapy resistance will
help design novel strategies to treat colorectal cancer. In this study, we
established an acquired 5-FU resistant cell line, LoVo-R, from LoVo cells.
Through exome sequencing, we discovered that elevated GLI1 signaling axis is a
major genetic alteration in the 5-FU resistant cells. Hh signaling, a pathway
essential for embryonic development, is an important regulator for residual
cancer cells. We demonstrated that knockdown of GLI1 or GLI2 sensitized LoVo-R
cells to 5-FU treatment, reduced cell invasiveness. The relevance of our studies
to colorectal cancer patients is reflected by our discovery that high expression
of GLI1 signaling molecules was associated with a high incidence of cancer
relapse and a shorter survival in a larger cohort of colorectal cancer patients
who underwent chemotherapy (containing 5-FU). Taken together, our data
demonstrate the critical role of the GLI1 signaling axis for 5-FU resistance in
colorectal cancer.
PMID- 28149502
TI - An open and transparent process to select ELIXIR Node Services as implemented by
ELIXIR-UK.
AB - ELIXIR is the European infrastructure established specifically for the sharing
and sustainability of life science data. To provide up-to-date resources and
services, ELIXIR needs to undergo a continuous process of refreshing the services
provided by its national Nodes. Here we present the approach taken by ELIXIR-UK
to address the advice by the ELIXIR Scientific Advisory Board that Nodes need to
develop " mechanisms to ensure that each Node continues to be representative of
the Bioinformatics efforts within the country". ELIXIR-UK put in place an open
and transparent process to identify potential ELIXIR resources within the UK
during late 2015 and early to mid-2016. Areas of strategic strength were
identified and Expressions of Interest in these priority areas were requested
from the UK community. Criteria were established, in discussion with the ELIXIR
Hub, and prospective ELIXIR-UK resources were assessed by an independent
committee set up by the Node for this purpose. Of 19 resources considered, 14
were judged to be immediately ready to be included in the UK ELIXIR Node's
portfolio. A further five were placed on the Node's roadmap for future
consideration for inclusion. ELIXIR-UK expects to repeat this process regularly
to ensure its portfolio continues to reflect its community's strengths.
PMID- 28413606
TI - Comparing efficacy of a sweep net and a dip method for collection of mosquito
larvae in large bodies of water in South Africa.
AB - In this study we tested an alternative method for collecting mosquito larvae
called the sweep net catch method and compared its efficiency to that of the
traditional dip method. The two methods were compared in various water bodies
within Kruger National Park and Lapalala Wilderness area, South Africa. The sweep
net catch method performed 5 times better in the collection of Anopheles larvae
and equally as well as the dip method in the collection of Culex larvae (p =8.58
x 10 -5). Based on 15 replicates the collector's experience level did not play a
significant role in the relative numbers of larvae collected using either method.
This simple and effective sweep net catch method will greatly improve the
mosquito larval sampling capacity in the field setting.
PMID- 28408973
TI - A multi-scale computational model of the effects of TMS on motor cortex.
AB - The detailed biophysical mechanisms through which transcranial magnetic
stimulation (TMS) activates cortical circuits are still not fully understood.
Here we present a multi-scale computational model to describe and explain the
activation of different pyramidal cell types in motor cortex due to TMS. Our
model determines precise electric fields based on an individual head model
derived from magnetic resonance imaging and calculates how these electric fields
activate morphologically detailed models of different neuron types. We predict
neural activation patterns for different coil orientations consistent with
experimental findings. Beyond this, our model allows us to calculate activation
thresholds for individual neurons and precise initiation sites of individual
action potentials on the neurons' complex morphologies. Specifically, our model
predicts that cortical layer 3 pyramidal neurons are generally easier to
stimulate than layer 5 pyramidal neurons, thereby explaining the lower
stimulation thresholds observed for I-waves compared to D-waves. It also shows
differences in the regions of activated cortical layer 5 and layer 3 pyramidal
cells depending on coil orientation. Finally, it predicts that under standard
stimulation conditions, action potentials are mostly generated at the axon
initial segment of cortical pyramidal cells, with a much less important
activation site being the part of a layer 5 pyramidal cell axon where it crosses
the boundary between grey matter and white matter. In conclusion, our
computational model offers a detailed account of the mechanisms through which TMS
activates different cortical pyramidal cell types, paving the way for more
targeted application of TMS based on individual brain morphology in clinical and
basic research settings.
PMID- 28413608
TI - Evidence synthesis and decision modelling to support complex decisions:
stockpiling neuraminidase inhibitors for pandemic influenza usage.
AB - Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a
defence against pandemic influenza is a significant public health policy decision
that must be made despite a lack of conclusive evidence from randomised
controlled trials regarding the effectiveness of NAIs on important clinical end
points such as mortality. The objective of this study was to determine whether
NAIs should be stockpiled for treatment of pandemic influenza on the basis of
current evidence. Methods: A decision model for stockpiling was designed. Data on
previous pandemic influenza epidemiology was combined with data on the
effectiveness of NAIs in reducing mortality obtained from a recent individual
participant meta-analysis using observational data. Evidence synthesis techniques
and a bias modelling method for observational data were used to incorporate the
evidence into the model. The stockpiling decision was modelled for adults (>=16
years old) and the United Kingdom was used as an example. The main outcome was
the expected net benefits of stockpiling in monetary terms. Health benefits were
estimated from deaths averted through stockpiling. Results: After adjusting for
biases in the estimated effectiveness of NAIs, the expected net benefit of
stockpiling in the baseline analysis was L444 million, assuming a willingness to
pay of L20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile
NAIs. There was a greater probability that the stockpile would not be utilised
than utilised. However, the rare but catastrophic losses from a severe pandemic
justified the decision to stockpile. Conclusions: Taking into account the
available epidemiological data and evidence of effectiveness of NAIs in reducing
mortality, including potential biases, a decision maker should stockpile anti
influenza medication in keeping with the postulated decision rule.
PMID- 28413609
TI - An ensemble-based Cox proportional hazards regression framework for predicting
survival in metastatic castration-resistant prostate cancer (mCRPC) patients.
AB - From March through August 2015, nearly 60 teams from around the world
participated in the Prostate Cancer Dream Challenge (PCDC). Participating teams
were faced with the task of developing prediction models for patient survival and
treatment discontinuation using baseline clinical variables collected on
metastatic castrate-resistant prostate cancer (mCRPC) patients in the comparator
arm of four phase III clinical trials. In total, over 2,000 mCRPC patients
treated with first-line docetaxel comprised the training and testing data sets
used in this challenge. In this paper we describe: (a) the sub-challenges
comprising the PCDC, (b) the statistical metrics used to benchmark prediction
performance, (c) our analytical approach, and finally (d) our team's overall
performance in this challenge. Specifically, we discuss our curated, ad-hoc,
feature selection (CAFS) strategy for identifying clinically important risk
predictors, the ensemble-based Cox proportional hazards regression framework used
in our final submission, and the adaptation of our modeling framework based on
the results from the intermittent leaderboard rounds. Strong predictors of
patient survival were successfully identified utilizing our model building
approach. Several of the identified predictors were new features created by our
team via strategically merging collections of weak predictors. In each of the
three intermittent leaderboard rounds, our prediction models scored among the top
four models across all participating teams and our final submission ranked 9 th
place overall with an integrated area under the curve (iAUC) of 0.7711 computed
in an independent test set. While the prediction performance of teams placing
between 2 nd- 10 th (iAUC: 0.7710-0.7789) was better than the current gold
standard prediction model for prostate cancer survival, the top-performing team,
FIMM-UTU significantly outperformed all other contestants with an iAUC of 0.7915.
In summary, our ensemble-based Cox regression framework with CAFS resulted in
strong overall performance for predicting prostate cancer survival and represents
a promising approach for future prediction problems.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in the visualisation of information since
Haeckel's time, phylogenetic visualisation has moved forward remarkably little.
In this brief essay, I give a short review of what I consider to be some recent
major advances, and outline a new kind of phylogenetic visualisation. This new
graphic, the fibre plot, uses the metaphor of sections through a tree to describe
change in a phylogeny. As an animation, I suggest it is a powerful method to help
interpret large phylogenetic hypotheses, although snapshots of it can also be
displayed. As we enter the Anthropocene, I argue there has never been a greater
need to know humanity's true place in the world, as depicted in the tree of life.
PMID- 28413611
TI - Expression of lectin-like transcript-1 in human tissues.
AB - Background: Receptor-ligand pairs of C-type lectin-like proteins have been shown
to play an important role in cross talk between lymphocytes, as well as in immune
responses within concrete tissues and structures, such as the skin or the
germinal centres. The CD161-Lectin-like Transcript 1 (LLT1) pair has gained
particular attention in recent years, yet a detailed analysis of LLT1
distribution in human tissue is lacking. One reason for this is the limited
availability and poor characterisation of anti-LLT1 antibodies. Methods: We
assessed the staining capabilities of a novel anti-LLT1 antibody clone (2H7),
both by immunohistochemistry and flow cytometry, showing its efficiency at LLT1
recognition in both settings. We then analysed LLT1 expression in a wide variety
of human tissues. Results: We found LLT1 expression in circulating B cells and
monocytes, but not in lung and liver-resident macrophages. We found strikingly
high LLT1 expression in immune-privileged sites, such as the brain, placenta and
testes, and confirmed the ability of LLT1 to inhibit NK cell function.
Conclusions: Overall, this study contributes to the development of efficient
tools for the study of LLT1. Moreover, its expression in different healthy human
tissues and, particularly, in immune-privileged sites, establishes LLT1 as a good
candidate as a regulator of immune responses.
PMID- 28413612
TI - Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in
blood pressure control and recent pivotal trials of RAAS blockade in heart
failure and diabetic nephropathy.
AB - The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the
physiology of blood pressure control and the pathophysiology of hypertension
(HTN) with effects on vascular tone, sodium retention, oxidative stress,
fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents
have been available to treat HTN since the 1970s and newer medications are being
developed. In this review, we will (1) examine new anti-hypertensive medications
affecting the RAAS, (2) evaluate recent studies that help provide a better
understanding of which patients may be more likely to benefit from RAAS blockade,
and (3) review three recent pivotal randomized trials that involve newer RAAS
blocking agents and inform clinical practice.
PMID- 28413614
TI - The PathLinker app: Connect the dots in protein interaction networks.
AB - PathLinker is a graph-theoretic algorithm for reconstructing the interactions in
a signaling pathway of interest. It efficiently computes multiple short paths
within a background protein interaction network from the receptors to
transcription factors (TFs) in a pathway. We originally developed PathLinker to
complement manual curation of signaling pathways, which is slow and painstaking.
The method can be used in general to connect any set of sources to any set of
targets in an interaction network. The app presented here makes the PathLinker
functionality available to Cytoscape users. We present an example where we used
PathLinker to compute and analyze the network of interactions connecting proteins
that are perturbed by the drug lovastatin.
PMID- 28413615
TI - Monitoring disease activity and severity in lupus.
AB - Background: Systemic lupus erythematosus (SLE) is a relatively uncommon disease
of young females in Pakistan. Usually, it has a relapsing-remitting course with
variable severity and disease activity. Amongst the different clinical and
laboratory parameters used to monitor disease activity in lupus, mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. This study
included 25 patients with active SLE, and another 25 participants with stable,
inactive lupus. MPV was measured in each group and compared using SPSS version
16. MPV was also correlated with SLE disease activity index (SLEDAI) and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Pearson's
correlation tests were applied. Sensitivity and specificity of MPV were checked
through ROC analysis. Results: The MPV of patients with active SLE (n=25, mean
[M]=7.12, SD=1.01) was numerically lower than those in the inactive-SLE group
(n=25, M= 10.12, SD=0.97), and this was statistically significant ( P<0.001). MPV
had an inverse relationship with both ESR (r=-0.93, P<0.001) and SLEDAI (r=
0.94, P<0.001). However, there was a strong positive correlation between ESR and
SLEDAI (r=0.95, P<0.001). For MPV, a cutoff value of less than 8.5fl had a
sensitivity of 92% and a specificity of 100% ( P< 0.001). Conclusions: Higher
disease activity in SLE is associated with a correspondingly low MPV.
PMID- 28413613
TI - The rise of photoresponsive protein technologies applications in vivo: a
spotlight on zebrafish developmental and cell biology.
AB - The zebrafish ( Danio rerio) is a powerful vertebrate model to study cellular and
developmental processes in vivo. The optical clarity and their amenability to
genetic manipulation make zebrafish a model of choice when it comes to applying
optical techniques involving genetically encoded photoresponsive protein
technologies. In recent years, a number of fluorescent protein and optogenetic
technologies have emerged that allow new ways to visualize, quantify, and perturb
developmental dynamics. Here, we explain the principles of these new tools and
describe some of their representative applications in zebrafish.
PMID- 28413616
TI - -A curated transcriptomic dataset collection relevant to embryonic development
associated with in vitro fertilization in healthy individuals and patients with
polycystic ovary syndrome.
AB - The collection of large-scale datasets available in public repositories is
rapidly growing and providing opportunities to identify and fill gaps in
different fields of biomedical research. However, users of these datasets should
be able to selectively browse datasets related to their field of interest. Here
we made available a collection of transcriptome datasets related to human
follicular cells from normal individuals or patients with polycystic ovary
syndrome, in the process of their development, during in vitro fertilization.
After RNA-seq dataset exclusion and careful selection based on study description
and sample information, 12 datasets, encompassing a total of 85 unique
transcriptome profiles, were identified in NCBI Gene Expression Omnibus and
uploaded to the Gene Expression Browser (GXB), a web application specifically
designed for interactive query and visualization of integrated large-scale data.
Once annotated in GXB, multiple sample grouping has been made in order to create
rank lists to allow easy data interpretation and comparison. The GXB tool also
allows the users to browse a single gene across multiple projects to evaluate its
expression profiles in multiple biological systems/conditions in a web-based
customized graphical views. The curated dataset is accessible at the following
link: http://ivf.gxbsidra.org/dm3/landing.gsp.
PMID- 28413617
TI - Automated Wormscan.
AB - There has been a recent surge of interest in computer-aided rapid data
acquisition to increase the potential throughput and reduce the labour costs of
large scale Caenorhabditis elegans studies. We present Automated WormScan, a low
cost, high-throughput automated system using commercial photo scanners, which is
extremely easy to implement and use, capable of scoring tens of thousands of
organisms per hour with minimal operator input, and is scalable. The method does
not rely on software training for image recognition, but uses the generation of
difference images from sequential scans to identify moving objects. This approach
results in robust identification of worms with little computational demand. We
demonstrate the utility of the system by conducting toxicity, growth and
fecundity assays, which demonstrate the consistency of our automated system, the
quality of the data relative to manual scoring methods and congruity with
previously published results.
PMID- 28357048
TI - Bibliometric analysis of Oropouche research: impact on the surveillance of
emerging arboviruses in Latin America.
AB - Given the emergence and reemergence of viral diseases, particularly in Latin
America, we would like to provide an analysis of the patterns of research and
publication on Oropouche virus (OROV). We also discuss the implications of recent
epidemics in certain areas of South America, and how more clinical and
epidemiological information regarding OROV is urgently needed.
PMID- 28413619
TI - Picopore: A tool for reducing the storage size of Oxford Nanopore Technologies
datasets without loss of functionality.
AB - Oxford Nanopore Technologies' (ONT) MinION and PromethION long-read sequencing
technologies are emerging as genuine alternatives to established Next-Generation
Sequencing technologies. A combination of the highly redundant file format and a
rapid increase in data generation have created a significant problem both for
immediate data storage on MinION-capable laptops, and for long-term storage on
lab data servers. We developed Picopore, a software suite offering three methods
of compression. Picopore's lossless and deep lossless methods provide a 25% and
44% average reduction in size, respectively, without removing any data from the
files. Picopore's raw method provides an 88% average reduction in size, while
retaining biologically relevant data for the end-user. All methods have the
capacity to run in real-time in parallel to a sequencing run, reducing demand for
both immediate and long-term storage space.
PMID- 28413620
TI - Case Report: Sciatic nerve schwannoma - a rare cause of sciatica.
AB - Herein we report a rare case of a sciatic nerve schwannoma causing sciatica in a
69-year-old female. Sciatic nerve schwannoma is a rare entity. It should always
be considered as a possible cause of sciatica in patients that present with
symptoms of sciatica with no prolapsed disc in the lumbar spine and a negative
crossed straight leg raise test. Timely diagnosis and complete excision of the
lesion leads to complete resolution of the symptoms of such patients.
PMID- 28413621
TI - Recent Advances in Pediatric Ventilatory Assistance.
AB - In this review on respiratory assistance, we aim to discuss the following recent
advances: the optimization and customization of mechanical ventilation, the use
of high-frequency oscillatory ventilation, and the role of noninvasive
ventilation. The prevention of ventilator-induced lung injury and diaphragmatic
dysfunction is now a key aspect in the management of mechanical ventilation,
since these complications may lead to higher mortality and prolonged length of
stay in intensive care units. Different physiological measurements, such as
esophageal pressure, electrical activity of the diaphragm, and volumetric
capnography, may be useful objective tools to help guide ventilator assistance.
Companies that design medical devices including ventilators and respiratory
monitoring platforms play a key role in knowledge application. The creation of a
ventilation consortium that includes companies, clinicians, researchers, and
stakeholders could be a solution to promote much-needed device development and
knowledge implementation.
PMID- 28413622
TI - Insight into skin cell-based osteogenesis: a review.
AB - For decades, researchers have been fascinated by the strategy of using cell
therapy for bone defects; some progress in the field has been made. Owing to its
ample supply and easy access, skin, the largest organ in the body, has gained
attention as a potential source of stem cells. Despite extensive applications in
skin and nerve regeneration, an increasing number of reports indicate its
potential use in bone tissue engineering and regeneration. Unfortunately, few
review articles are available to outline current research efforts in skin-based
osteogenesis. This review first summarizes the latest findings on stem cells or
progenitors in skin and their niches and then discusses the strategies of skin
cell-based osteogenesis. We hope this article elucidates this topic and generates
new ideas for future studies.
PMID- 28413624
TI - Recent advances in understanding spondyloarthritis.
AB - This review is concerned with a number of recent publications that contribute to
current thinking on the pathogenesis of spondyloarthritis. The areas covered
include the lymphocyte population in the enthesis, which is thought to drive
enthesitis, and hence clinical manifestations. The debate on how HLA-B27 is
implicated in inflammation is also considered, together with recent and
contradictory evidence on the effects of the peptide-trimming enzyme ERAP1 on B27
expression and hence susceptibility to spondylitis. Lastly, a recent report on
the role of the gut microbiome in an important model of spondyloarthritis is
considered.
PMID- 28413623
TI - Glutamate plasticity woven through the progression to alcohol use disorder: a
multi-circuit perspective.
AB - Glutamate signaling in the brain is one of the most studied targets in the
alcohol research field. Here, we report the current understanding of how the
excitatory neurotransmitter glutamate, its receptors, and its transporters are
involved in low, episodic, and heavy alcohol use. Specific animal behavior
protocols can be used to assess these different drinking levels, including two
bottle choice, operant self-administration, drinking in the dark, the alcohol
deprivation effect, intermittent access to alcohol, and chronic intermittent
ethanol vapor inhalation. Importantly, these methods are not limited to a
specific category, since they can be interchanged to assess different states in
the development from low to heavy drinking. We encourage a circuit-based
perspective beyond the classic mesolimbic-centric view, as multiple structures
are dynamically engaged during the transition from positive- to negative-related
reinforcement to drive alcohol drinking. During this shift from lower-level
alcohol drinking to heavy alcohol use, there appears to be a shift from
metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate
receptor-related processes. Despite high efficacy of the glutamate-related
pharmaceutical acamprosate in animal models of drinking, it is ineffective as
treatment in the clinic. Therefore, research needs to focus on other promising
glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms
or both.
PMID- 28413625
TI - HIV-associated neurocognitive disorders: recent advances in pathogenesis,
biomarkers, and treatment.
AB - HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma
viral suppression by antiretroviral agents. In fact, the prevalence of milder
subtypes of cognitive impairment is increasing. Neuropsychologic testing remains
the "gold standard" of diagnosis; however, this is time consuming and costly in a
resource-poor environment. Recently developed screening tools, such as CogState
and the revised HIV dementia scale, have very good sensitivity and specificity in
the more severe stages of HAND. However, questions remain regarding the utility
of, optimal population for, and insensitivity of tests in mild HAND. Recognition
of ongoing viral persistence and the inflammatory milieu in the central nervous
system (CNS) has advanced our understanding of the pathogenesis of HAND and
facilitated the development of biomarkers of CNS disease. The importance of the
monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral
proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor
neurotropism has been identified. Whilst biomarkers demonstrate monocyte
activation, inflammation, and neuronal injury, they remain limited in their
clinical utility. The improved understanding of pathogenic mechanisms has led to
novel approaches to the treatment of HAND; however, despite these advances, the
optimal management is still undefined.
PMID- 28413627
TI - Advancing psychological therapies for chronic pain.
AB - There is a strong tradition of therapy development and evaluation in the field of
psychological interventions for chronic pain. However, despite this research
production, the effects of treatments remain uncertain, and treatment development
has stalled. This review summarises the current evidence but focusses on
promising areas for improvement. Advancing psychological therapies for chronic
pain will come from a radical re-imagining of the content, delivery, place, and
control of therapy. The next generation of therapeutic interventions will also
need alternative methods of measurement and evaluation, and options are
discussed.
PMID- 28413626
TI - Non-infectious chemotherapy-associated acute toxicities during childhood acute
lymphoblastic leukemia therapy.
AB - During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be
affected by severe acute side effects, the most common being opportunistic
infections, mucositis, central or peripheral neuropathy (or both), bone
toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction
syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and
hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase
associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non
infectious acute toxicities are associated with clinically useful risk factors,
and across study groups there has been wide diversity in toxicity definitions,
capture strategies, and reporting, thus hampering meaningful comparisons of
toxicity incidences for different leukemia protocols. Since treatment of acute
lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there
is a need for strategies for assessing the burden of toxicities in the overall
evaluation of anti-leukemic therapy programs.
PMID- 28413628
TI - American Society for Enhanced Recovery (ASER) and Perioperative Quality
Initiative (POQI) Joint Consensus Statement on Optimal Analgesia within an
Enhanced Recovery Pathway for Colorectal Surgery: Part 2-From PACU to the
Transition Home.
AB - BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating
pain should be multifaceted and the goal should be to deliver "optimal
analgesia", which we define in this paper as a technique that optimizes patient
comfort and facilitates functional recovery with the fewest medication side
effects. METHODS: With input from a multidisciplinary, international group of
experts and through a structured review of the literature and use of a modified
Delphi method, we achieved consensus surrounding the topic of optimal analgesia
in the perioperative period for colorectal surgery patients. DISCUSSION: As a
part of the first Perioperative Quality Improvement (POQI) workgroup meeting, we
sought to develop a consensus document describing a comprehensive, yet rational
and practical, approach for developing an evidence-based plan for achieving
optimal analgesia, specifically for a colorectal surgery within an ERP. The goal
was twofold: (a) that application of this process would lead to improved patient
outcomes and (b) that investigation of the questions raised would identify
knowledge gaps to aid the direction for research into analgesia within ERPs in
the years to come. This document details the evidence for a wide range of
analgesic components, with particular focus on care in the post-anesthesia care
unit, general care ward, and transition to home after discharge. The preoperative
and operative consensus statement for analgesia was covered in Part 1 of this
paper. The overall conclusion is that the combination of analgesic techniques
employed in the perioperative period is not important as long as it is effective
in delivering the goal of "optimal analgesia" as set forth in this document.
PMID- 28413631
TI - Screening and contact precautions - A survey on infection control measures for
multidrug-resistant bacteria in German university hospitals.
AB - To assess the scope of infection control measures for multidrug-resistant
bacteria in high-risk settings, a survey among university hospitals was
conducted. Fourteen professionals from 8 sites participated. Reported policies
varied largely with respect to the types of wards conducting screening, sample
types used for screening and implementation of contact precautions. This
variability among sites highlights the need for an evidence-based consensus of
current infection control policies.
PMID- 28413629
TI - American Society for Enhanced Recovery (ASER) and Perioperative Quality
Initiative (POQI) joint consensus statement on optimal analgesia within an
enhanced recovery pathway for colorectal surgery: part 1-from the preoperative
period to PACU.
AB - BACKGROUND: Within an enhanced recovery pathway (ERP), the approach to treating
pain should be multifaceted and the goal should be to deliver "optimal
analgesia," which we define in this paper as a technique that optimizes patient
comfort and facilitates functional recovery with the fewest medication side
effects. METHODS: With input from a multi-disciplinary, international group of
clinicians, and through a structured review of the literature and use of a
modified Delphi method, we achieved consensus surrounding the topic of optimal
analgesia in the perioperative period for colorectal surgery patients.
DISCUSSION: As a part of the first Perioperative Quality Improvement (POQI)
workgroup meeting, we sought to develop a consensus document describing a
comprehensive, yet rational and practical, approach for developing an evidence
based plan for achieving optimal analgesia, specifically for a colorectal surgery
ERP. The goal was two-fold: (a) that application of this process would lead to
improved patient outcomes and (b) that investigation of the questions raised
would identify knowledge gaps to aid the direction for research into analgesia
within ERPs in the years to come. This document details the evidence for a wide
range of analgesic components, with particular focus from the preoperative period
to the post-anesthesia care unit. The overall conclusion is that the combination
of analgesic techniques employed in the perioperative period is not important as
long as it is effective in delivering the goal of optimal analgesia as set forth
in this document.
PMID- 28413632
TI - Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate
Surgical Education?
AB - BACKGROUND: Essentials Skills in the Management of Surgical Cases - ESMSC is an
International Combined Applied Surgical Science and Wet Lab course addressed at
the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical
Education and various Simulation-Based Learning (SBL) models have been endorsed.
This study aims to explore if there is any significant difference in delegates'
performance depending on whether they completed In Vivo module prior to the
equivalent in the laparoscopic simulator. MATERIALS AND METHODS: 37 Medical
Students from various EU countries were divided in 2 groups, and both completed
the "Fundamentals in Laparoscopic Surgery" module in the Dry-lab Laparoscopic
Simulator as well as the same module "In Vivo" on a swine model. Group A (18
students, 48.6%) completed the "Fundamentals in Laparoscopic Surgery - FLS"
module prior to the "In Vivo", whereas group B completed the "In Vivo" module
first. Direct Observation of Procedural Skills (DOPS) were used to assess
delegates' performance. RESULTS: The mean DOPS scores for the "FLS" and "In Vivo"
models were 2.27 +/- 0.902 and 2.03 +/- 0.833, respectively, and the delegates'
performance was not statistically significantly different between them (p =
0.128). There was no statistically significant difference in the scores among
different gender, year of study, school and handedness groups. The alteration in
the sequence between Dry-lab "FLS" and "In Vivo" modules did not affect the
performance in neither the "FLS" nor the "In Vivo" models. CONCLUSIONS: The
inexpensive, but low-fidelity "FLS" model could serve an equal alternative
Simulation-Based Learning model for the early undergraduate training. Our study
demonstrated that high fidelity In Vivo simulation for laparoscopic skills does
not affect significantly the improvement in the delegates' performance at the
undergraduate level. Further studies should be conducted to identify at which
stage of training should high fidelity simulation be introduced.
PMID- 28413630
TI - Patient healthcare trajectory. An essential monitoring tool: a systematic review.
AB - BACKGROUND: Patient healthcare trajectory is a recent emergent topic in the
literature, encompassing broad concepts. However, the rationale for studying
patients' trajectories, and how this trajectory concept is defined remains a
public health challenge. Our research was focused on patients' trajectories based
on disease management and care, while also considering medico-economic aspects of
the associated management. We illustrated this concept with an example: a
myocardial infarction (MI) occurring in a patient's hospital trajectory of care.
The patient follow-up was traced via the prospective payment system. We applied a
semi-automatic text mining process to conduct a comprehensive review of patient
healthcare trajectory studies. This review investigated how the concept of
trajectory is defined, studied and what it achieves. METHODS: We performed a
PubMed search to identify reports that had been published in peer-reviewed
journals between January 1, 2000 and October 31, 2015. Fourteen search questions
were formulated to guide our review. A semi-automatic text mining process based
on a semantic approach was performed to conduct a comprehensive review of patient
healthcare trajectory studies. Text mining techniques were used to explore the
corpus in a semantic perspective in order to answer non-a priori questions.
Complementary review methods on a selected subset were used to answer a priori
questions. RESULTS: Among the 33,514 publications initially selected for
analysis, only 70 relevant articles were semi-automatically extracted and
thoroughly analysed. Oncology is particularly prevalent due to its already well
established processes of care. For the trajectory thema, 80% of articles were
distributed in 11 clusters. These clusters contain distinct semantic information,
for example health outcomes (29%), care process (26%) and administrative and
financial aspects (16%). CONCLUSION: This literature review highlights the recent
interest in the trajectory concept. The approach is also gradually being used to
monitor trajectories of care for chronic diseases such as diabetes, organ failure
or coronary artery and MI trajectory of care, to improve care and reduce costs.
Patient trajectory is undoubtedly an essential approach to be further explored in
order to improve healthcare monitoring.
PMID- 28413633
TI - Pluripotent stem cells to hepatocytes, the journey so far.
AB - Over the past several years, there has been substantial progress in the field of
regenerative medicine, which has enabled new possibilities for research and
clinical application. For example, there are ongoing efforts directed at
generating functional hepatocytes from adult-derived pluripotent cells for
toxicity screening, generating disease models or, in the longer term, for the
treatment of liver failure. In the present review, the authors summarise recent
developments in regenerative medicine and pluripotent stem cells, the methods and
tissues used for reprogramming and the differentiation of induced pluripotent
stem cells (iPSCs) into hepatocyte-like cells. In addition, the hepatic disease
models developed using iPSC technologies are discussed, as well as the potential
for gene editing.
PMID- 28413634
TI - Involvement of regucalcin gene promoter region-related protein-p117, a
transcription factor, in human obesity.
AB - Regucalcin gene promoter region-related protein-p117 (RGPR-p117; gene symbol,
rgpr-117) was identified in 2001 as a novel transcription factor that
specifically binds to a nuclear factor I consensus motif, TTGGC(N)6CC in the
promoter region of the regucalcin (rgn) gene. The human RGPR-p117 gene consists
of 26 exons spanning ~4.1 kbp and is localized on chromosome 1q25.2. The nuclear
translocation of cytoplasm RGPR-p117 is mediated via the protein kinase C
dependent signaling pathway. Overexpression of RGPR-p117 enhances the
transcription activity of rgn, and a protective effect on cell death by
inhibition of gene expression levels of caspase-3, caspase-8 and FADD proteins
that possess the TTGGC motif in the promoter region of those genes was revealed.
RGPR-p117 has a crucial role as a transcription factor. Notably, RGPR-p117 was
shown to localize in the plasma membranes, mitochondria and microsomes
(endoplasmic reticulum; ER). RGPR-p117, which is located in the ER, was also
shown to have a role as an ER export factor implicated in the transports of
proteins and lipids. As a result of this finding, it was proposed in 2007 that
RGPR-p117 is renamed SEC 16 homolog B, endoplasmic reticulum export factor
(SEC16B). Recently, there is increasing evidence that RGPR-p117/SEC16B may be
involved in human obesity. Thus, the current review presents data regarding the
involvement of RGPR-p117 in human obesity.
PMID- 28413635
TI - Role of amyloid beta protein receptors in mediating synaptic plasticity.
AB - There are few diseases in modern biomedicine that have garnered as much
scientific interest and public concern as Alzheimer's disease (AD). The amyloid
hypothesis has become the dominant model of AD pathogenesis; however, the details
of the hypothesis are changing over time. Recently, given the increasing
recognition, subtle effects of amyloid beta protein (Abeta) on synaptic efficacy
may be critical to AD progression. Synaptic plasticity is the important
neurochemical foundation of learning and memory. Recent studies have identified
that soluble Abeta oligomers combine with certain receptors to impair synaptic
plasticity in AD, which advanced the amyloid hypothesis. The aim of the present
review was to summarize the role of Abeta-relevant receptors in regulating
synaptic plasticity and their downstream signaling cascades, which may provide
novel insights into the understanding of the pathogenesis of AD and the
development of therapeutic strategies to slow down the progression of AD
associated memory decline in the early stages.
PMID- 28413636
TI - Nuclear magnetic resonance metabolomics and human liver diseases: The principles
and evidence associated with protein and carbohydrate metabolism.
AB - During the last decade, metabolomics has become widely used in the field of human
diseases. Numerous studies have demonstrated that this is a powerful technique
for improving the understanding, diagnosis and management of various types of
liver disease, such as acute and chronic liver diseases, and liver
transplantation. Nuclear magnetic resonance (NMR) spectroscopy is one of the two
most commonly applied methods for metabolomics. The aim of the present review was
to investigate the results from recent key publications focusing on aspects of
protein and carbohydrate metabolism. The review includes existing procedures,
which are currently used for NMR data acquisition and statistical analysis. In
addition, notable results obtained by these studies on protein and carbohydrate
metabolism concerning human liver diseases are presented.
PMID- 28413637
TI - Correlation of survivin and B-cell lymphoma 2 expression with pathological
malignancy and anti-apoptotic properties of glial cell tumors.
AB - Apoptosis, whose mechanism remains unclear, is regulated by multiple factors. B
cell lymphoma 2 (Bcl-2) is a well-known anti-apoptotic mediator. Survivin is also
a recently recognized novel family inhibitor of apoptosis protein, which inhibits
apoptosis via a pathway distinct from Bcl-2 family members. Survivin and Bcl-2
are expressed in various types of human cancer. In the present study, survivin
and Bcl-2 expression were characterized in glial cell tumors, and the correlation
with pathological malignancy and anti-apoptotic properties were investigated.
Fifty-eight patients who had undergone surgical resection for glial cell tumors
were evaluated. The pathological types of glial cell tumors were categorized
according to the World Health Organization classification. Survivin and Bcl-2
expression levels were investigated by western blot analysis, and apoptosis was
detected by DNA fragmentation analysis. The anti-apoptotic rate of glial cell
tumors was calculated in tumor samples according to the expression of survivin
and Bcl-2 or co-expression. Survivin was characterized in 60.3%, and Bcl-2 was
expressed in 43.1% of glioma samples. Co-expression of survivin and Bcl-2 was
observed in 25.9% of the tumor specimens. Survivin expression in astrocytic
tumors was identified to be significantly associated with the pathological grade
(P<0.05); however, Bcl-2 was not (P>0.05). Anti-apoptotic rate of glial cell
tumors were detected in 91.4, 92.0 and 100% of patients exhibiting survivin, Bcl
2 or co-expression, respectively. However, the difference in anti-apoptotic
frequency between the three groups was not identified to be statistically
significant (P>0.05). The present study suggests that survivin expression is
correlated with pathological grades of gliomas. In addition, the expression of
survivin or Bcl-2 exerts potent anti-apoptotic properties in gliomas. Thus,
survivin or Bcl-2 may serve as potential targets for inducing the apoptosis of
gliomas.
PMID- 28413638
TI - Serologic testing of a panel of five antibodies in inflammatory bowel diseases:
Diagnostic value and correlation with disease phenotype.
AB - The aim of the present study was to evaluate the diagnostic value of five
serological antibodies, perinuclear antineutrophil cytoplasmic antibody (pANCA),
anti-Saccharomyces cerevisiae antibodies [ASCA; ASCA-immunoglobulin (IgG)and ASCA
IgA], Escherichia coli outer membrane porin C antibody (anti-OmpC) and CBir1
flagellin antibody for detection in inflammatory bowel diseases. Whether the
antibody status correlated with the disease phenotype was also evaluated. Sera
from 71 patients with Crohn's disease (CD), 41 patients with ulcerative colitis
(UC), 78 patients with other gastrointestinal diseases and 31 healthy control
subjects were investigated. Clinical data were gathered at the time of serum
sampling and enzyme-linked immunosorbent assay was used to determine titers of
the above mentioned five antibodies. The pANCA test exhibited a sensitivity of
53.7% for UC and the ASCA test had a sensitivity of 66.2% for CD. The prevalence
of anti-OmpC was significantly higher in CD than in intestinal tuberculosis (TB),
indicating that anti-OmpC may be a serologic marker distinguishing CD from TB.
The pANCA+/ASCA- exhibited the best specificity for differentiating between CD
and UC. In UC, the presence of pANCA was greater in the patients with moderate to
severe activity than in those with mild activity. ASCA was more positive in ileal
CD. Furthermore, positive ASCA-IgG or anti-OmpC implied that complicated CD and
pANCA was associated with colonic CD. Seropositivity of anti-CBir1 was lowest in
colonic CD.
PMID- 28413639
TI - Calprotectin in serum and zonulin in serum and feces are elevated after
introduction of a diet with lower carbohydrate content and higher fiber, fat and
protein contents.
AB - Calprotectin is a marker of inflammation and zonulin is a marker of intestinal
permeability. Diets with lower carbohydrate content and higher contents of fat,
fiber and protein, e.g., Okinawan-based diet, are considered to reduce
inflammation and intestinal permeability. The aim of the present study was to
evaluate calprotectin and zonulin levels in serum and feces after intervention
with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2
diabetes, mean age 57.5+/-8.2 years, BMI 29.9+/-4.1 kg/m2, were served the diet
during 12 weeks, and were followed for another 16 weeks. Anthropometric and
metabolic parameters were registered. Fasting levels of calprotectin and zonulin
in serum and feces, and hormones in plasma, were measured by Luminex or ELISA
before study start and after 12 and 28 weeks. Calprotectin in serum tended to be
increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated
after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28
weeks (P=0.014). In contrast to baseline, there was a correlation between
calprotectin and zonulin in serum and feces after dietary intervention (P=0.025
vs. P=0.079). Energy percentage of protein in breakfast correlated with serum
calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059).
Calprotectin in serum tended to be elevated, and zonulin in serum and feces are
elevated after introduction of an Okinawan-based Nordic diet. These biomarkers
correlate with energy percentage of protein.
PMID- 28413640
TI - Clinicopathological examination of dipeptidase 1 expression in colorectal cancer.
AB - Dipeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is fundamental
in glutathione and leukotriene metabolism. DPEP1 was initially considered as a
tumor suppressor gene in Wilms' tumor and breast cancer. However, it has been
reported that DPEP1 is upregulated in colorectal cancers (CRCs) and high DPEP1
expression levels are associated with poorer patient survival. The role of DPEP1
genes in CRC, as well as their expression, requires investigation. Therefore, the
present study investigated DPEP1 expression using reverse transcription
quantitative polymerase chain reaction or immunohistochemistry on surgically
resected samples from CRC cases, and further examined the biological significance
of DPEP1 by comparing the expression of the epithelial to mesenchymal transition
(EMT) markers, including epithelial cadherin and Vimentin to clarify the function
of DPEP1 in CRC, particularly in metastasis. The level of DPEP1 expression was
identified to be significantly increased in tumorous tissue samples compared with
that in non-tumorous tissue samples. In addition, increased DPEP1 mRNA expression
levels were associated with positive lymph node metastasis in the included
cohort. However, no positive correlations were observed between DPEP1 and EMT
markers in the cohort. The results indiciates that further investigations into
the upregulation of DPEP1 in colorectal carcinogenesis and the role of
therapeutic or prognostic biomarkers are required.
PMID- 28413641
TI - Serum miR-20a is a promising biomarker for gastric cancer.
AB - Gastric cancer (GC) is a common type of cancer, particularly in China. Numerous
studies have demonstrated that circulating microRNAs (miRNAs) have potential
applications as noninvasive biomarkers for cancer diagnosis and prognosis.
Microarray-based serum miRNA profiling was performed on the serum of 12 paired
pre- and post-operative GC patients to screen differentially expressed serum
miRNAs. Twelve different serum miRNAs between pre- and post-operative GC patients
were identified. Those miRNAs were verified by real-time quantitative polymerase
chain reaction in 110 paired pre- and post-operative serum samples from 55 GC
patients. miR-20a was confirmed and demonstrated potential as a GC-associated
biomarker. Furthermore, the levels of serum miR-20a were significantly different
between GC, nasopharyngeal cancer, colorectal carcinoma, breast cancer and non
cancerous controls. In addition, it was found that serum miR-20a levels
correlated with age, tumor stage, differentiated degree and lymph node metastasis
in GC. Survival analysis indicated that GC patients with elevated levels of serum
miR-20a had poor survival. Thus, serum miR-20a may serve as a molecular marker
for diagnosis, evaluating therapeutic efficacy and prognosis, as well as
monitoring recurrence in GC patients.
PMID- 28413642
TI - Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury.
AB - Trimethyltin (TMT) is a potent neurotoxicant that affects various regions within
the central nervous system, including the neocortex, cerebellum, and hippocampus.
In the present study, ginsenoside Rd was investigated as a candidate
neuroprotective agent in a primary hippocampal neuron culture and mouse models.
TMT induced neurotoxicity in a seven-day primary hippocampal neuron culture in a
dose-dependent manner (2.5-10 uM). However, pre-treatment with 20 ug/ml
ginsenoside Rd for 24 h reversed the toxic action. ICR mice were administered a
single injection of 2 mg/kg body weight TMT. Apparent tremor seizure and impaired
passive avoidance tests demonstrated significant differences when compared with a
saline treated control group. Nissl staining was performed to evaluate the
neuronal loss in the hippocampus. In addition, immunostaining of glial fibrillary
acidic protein characterized the features of astroglial activation. These results
demonstrated that TMT markedly induced Cornu Ammonis 1 subregion neuronal loss
and reactive astrocytes in the hippocampus, indicating disrupted hippocampal
function. Notably, ginsenoside Rd attenuated the tremor seizures and cognitive
decline in behavioral tests. Additionally, significantly reduced neuronal loss
(P=0.018) and active astroglials (P=0.003) were observed in the ginsenoside Rd
treated group. Ginsenoside Rd prevented TMT-induced cell apoptosis via regulation
of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 and caspase-3. These results
demonstrate that ginsenoside may be developed as a neuroprotective agent to
prevent TMT-induced neurotoxicity.
PMID- 28413643
TI - Cytotoxic and antimigratory effects of Cratoxy formosum extract against HepG2
liver cancer cells.
AB - The aim of the present study was to investigate the molecular mechanisms
underlying Cratoxylum formosum (CF) Dyer-induced cancer cell death and
antimigratory effects in HepG2 liver cancer cells. The cytotoxic,
antiproliferative and antimigratory effects of CF leaf extract on human liver
cancer HepG2 cell lines were evaluated using sulforhodamine B, colony formation,
and wound healing assays. In addition, apoptosis induction mechanisms were
investigated via reactive oxygen species (ROS) formation, caspase 3 activities,
and mitochondrial membrane potential (DeltaPsim) disruption. Gene expression and
apoptosis-associated protein levels were measured by reverse transcription
quantitative polymerase chain reaction and western blotting. CF induced HepG2
cell death in a time- and dose-dependent manner with half maximal inhibitory
concentration values of 219.03+/-9.96 and 124.90+/-6.86 ug/ml at 24 and 48 h,
respectively. Treatment with CF caused a significant and dose-dependent decrease
in colony forming ability and cell migration. Furthermore, the present study
demonstrated that CF induced ROS formation, increased caspase 3 activities,
decreased the DeltaPsim, and caused HepG2 apoptosis. CF marginally decreased the
expression level of the cell cycle regulatory protein, ras-related C3 botulinum
toxin substrate 1 (rho family, small GTP binding protein Rac1) and the downstream
protein, cyclin dependent kinase 6. Additionally, CF significantly enhanced p21
levels, reduced cyclin D1 protein levels and triggered cancer cell death. CF leaf
extracts induced cell death, stimulated apoptosis and inhibited migration in
HepG2 cells. Thus, CF may be useful for developing an anticancer drug candidate
for the treatment of liver cancer.
PMID- 28413644
TI - Reduction in miRNA-125b-5p levels is associated with obstructive renal injury.
AB - Obstructive renal injury is a common disease that leads to progressive
glomerulosclerosis, tubulointerstitial fibrosis and loss of renal function.
MicroRNAs (miRNAs/miRs) are small non-coding molecules that may be involved in
the progression of many renal diseases. The aim of the present study was to
investigate the roles of miRNAs, including miR-125b, miR-326 and miR-324p, in
obstructive renal injury. Blood samples were collected from 91 patients with
ureteral obstruction and 76 controls to examine renal function. In addition, the
levels of miR-125b, miR-326 and miR-324p in patients with ureteral obstruction
and controls were determined by the reverse transcription-quantitative polymerase
chain reaction. Furthermore, the relationship between miRNA levels and renal
function was evaluated by the Mann-Whitney U test. Upregulated levels of serum
creatinine (SCr) in patients with ureteral obstruction were observed, identifying
the injury of renal function. Although the expression levels of miR-324-5p [1.003
(0.391-2.279) vs. 0.934 (0.579-1.539), P=0.300] and miR-326 [0.840 (0.180-2.020)
vs. 0.949 (0.507-1.702), P=0.050] presented no significant difference, the levels
of miR-125b-5p [0.755 (0.210-2.110) vs. 0.960 (0.390-1.770), P=0.002] in patients
with ureteral obstruction were significantly lower than those in controls. These
results indicated that there is a stronger correlation of miR-125b-5p with the
occurrence of ureteral obstruction, especially for the female (P=0.0171) and
elderly (P=0.0142). Furthermore, the levels of miR-125b-5p (r=-0.175, P=0.038)
were closely associated with the serum levels of SCr, suggesting a key role of
miR-125b-5p in renal dysfunction. Thus, these findings suggested that miR-125b-5p
in patients with ureteral obstruction correlated with renal function, and may be
a potential biomarker for obstructive renal injury.
PMID- 28413645
TI - Long non-coding RNA CCAT1 is overexpressed in oral squamous cell carcinomas and
predicts poor prognosis.
AB - Oral squamous cell carcinoma (SCC) is the most common malignant tumor in India
with 5-year survival rates totaling <50%. Recently, dysregulation of non-coding
RNA was reported as a potential hallmark of carcinogenesis. Colon Cancer
Associated Transcript 1 (CCAT1), an lncRNA located in chromosome 8q24, close to
the c-Myc gene, has been reported to be overexpressed in many human cancers. In
the present study, the authors analyzed the expression of CCAT1, c-Myc and the
miRNAs miR155-5p, let7b-5p, miR490-3p and miR218-5p sponged by CCAT1 in 60 oral
tumor and 8 normal tissue samples by reverse transcription-quantitative
polymerase chain reaction. CCAT1 was significantly overexpressed in 27% (16/60)
of oral tumors. Interestingly, a high level of c-Myc expression was observed in
all CCAT1 overexpressing cases (P=0.0473). Furthermore, CCAT1 overexpression
significantly downregulated miR155-5p (P=0.03) and let7b-5p (P<0.0001). Oral
cancer cases expressing high level of CCAT1 (P=0.01) presented poor therapeutic
outcome. To the best of the authors' knowledge, this is the first study to report
the overexpression of the CCAT1 in oral SCCs, and the results suggested that
CCAT1 overexpression may sponge miR155-5p and let7b-5p, and may account for poor
treatment response.
PMID- 28413646
TI - Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the
glycolysis pathway in tumors.
AB - High aerobic glycolysis, as one of the hallmarks of cancer cells, requires
nicotinamide adenine dinucleotide (NAD+) as a vital co-factor, to guarantee the
flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer
metabolism, is a source of NAD+ additional to lactate dehydrogenase (LDH). The
current study aimed to elucidate the kinetic parameters of MDH in human breast
cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis
Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the
crude extracts of human breast tumors and healthy tissue samples, which were
obtained directly from the operating theatre. To assess the potential role of MDH
in supporting glycolysis, the MDH activity was measured when the LDH activity was
inhibited by different concentrations of oxamate, an inhibitor of LDH in breast
cancer cell lines. The Km of cancerous MDH (C-MDH) was the same as the healthy
MDH, although the Vmax of C-MDH was higher relative to the healthy MDH. Notably,
the MDH activity was increased in the MDA-MB-231 cell line, which was treated
with the LDH inhibitor (oxamate), but not in the MCF-7 cell line (P<0.05). The
higher tendency of C-MDH for NAD+ and malate generation in cancer cells is an
effective approach for supporting glycolysis. Increasing MDH activity in the
absence of LDH demonstrates the supportive role of MDH in glycolysis. Therefore,
decreasing MDH activity and expression in a forward reaction may present as a
valid molecular target to abolish its potential effect on tumor metabolism.
PMID- 28413647
TI - Nigella sativa seed extract attenuates the fatigue induced by exhaustive swimming
in rats.
AB - In previous studies, Nigella sativa (NS) has been studied due to its various
physiological and pharmacological activities. However, evidence on the effects of
NS on physical fatigue following exhaustive swimming remains limited. In the
present study, the authors evaluated the potential beneficial effects of NS
against the fatigue activity following exhaustive swimming. Rats were orally
administered with NS extract (2 g/kg/day) for 21 days, and the anti-fatigue
effect was assessed by exhaustive swimming exercise. The presented results
indicated that pre-treatment of NS extract significantly increased the time to
exhaustion. In hemodynamic parameters, NS extract increased blood pO2 and O2sat,
but decreased pCO2. For underlying mechanisms, NS extract protected depletion of
energy, indicated by increased levels of blood pH, glucose and tissue glycogen
contents, and decreased levels of blood lactate, tissue lactic dehydrogenase and
creatine kinase, when the NS extract was pre-treated. In addition, the NS extract
inhibited oxidative stress following exhaustive swimming, as reflected by the
results of increased levels of superoxide dismutase and redox ratio, and
decreased the level of malondialdehyde when the NS extract was pre-treated.
Collectively, the present study demonstrated that NS extract has an anti-fatigue
activity against exhaustive swimming by energy restoration and oxidative-stress
defense.
PMID- 28413648
TI - Effects of hyperbaric oxygen treatment on gastric cancer cell line SGC7901.
AB - Hyperbaric oxygen (HBO) has been previously identified as an effective adjunct
treatment option for the management of brain injury, diabetic ulcers and chronic
wounds. However, the roles of HBO as an adjunctive therapy for tumors remain
controversial. The present research project was performed to explore the effects
of HBO treatment on proliferation, autophagy and endoplasmic reticulum stress
response of the gastric cancer cell line, SGC7901. The present study demonstrated
that, after subjecting SGC7901 cells to HBO treatment, the increase in cell
proliferation was significant, compared with that of the control group. In
addition, there was a significant increase in LC3-phosphatidylethanolamine
conjugate (LC3-II) level, as well as binding immunoglobulin protein level, and a
significant decrease in CCAAT-enhancer-binding protein homologous protein level.
These suggested that hyperbaric oxygen treatment alone may promote proliferation
and cell survival of gastric cancer cell SGC7901, and inhibit apoptosis through
regulating cell autophagy and oxidative stress.
PMID- 28413649
TI - Hazardous factors besides infection in hypoglycemia.
AB - Hypoglycemia is one of the most common issues encountered in daily emergency
practice. In addition to the treatment of hypoglycemia, certain other situations
concomitant with hypoglycemia require further treatment. The aim of the present
study was to compare demographic and clinical characteristics of infected
[urinary tract infection (UTI), pneumonia or biliary tract infection (BTI)] vs.
non-infected hypoglycemic patients to establish which hypoglycemic patients
required further observation or hospitalization. This was a retrospective cross
sectional study of hypoglycemic (<60 mg/dl) hospitalized patients. The patients
were divided into two groups: Those with hypoglycemia and concurrent infection
(UTIs, pneumonia or BTIs; n=103) and non-infected hypoglycemic patients (n=83).
Student's t-test was performed to analyze continuous data and the chi2 test was
used to analyze categorical data. Infections included 62 UTI, 43 pneumonia and 5
BTI. Comparing between the infected and non-infected groups, no significant
differences were identified between mean glucose or body temperature, concurrent
diagnosis (liver cirrhosis, uremia, acute renal failure, stroke or cancer) or
mortality rate. Compared with the non-infected subjects, the infected patients
were significantly older and had a significantly higher female ratio, as well as
increased heart rates, white blood cell count and C-reactive protein levels. The
present study proposes that characteristics, including concurrent stroke, liver
cirrhosis and cancer are a point of focus in the initial management of
hospitalized hypoglycemic patients.
PMID- 28413650
TI - Clinical features of hemodialysis patients treated for hepatocellular carcinoma:
Comparison between resection and radiofrequency ablation.
AB - There is no consensus regarding which therapeutic option is better and/or safer
for treating hemodialysis (HD) patients with hepatocellular carcinoma (HCC). The
present study compared surgical resection (Hx) and radiofrequency ablation (RFA)
with regard to therapeutic efficacy in HD patients with HCC. Of 108 HD patients
with naive HCC treated at 15 institutions between 1988 and 2014 enrolled in the
present study, 58 fulfilled the up-to-7 criteria [7 as the sum of the size of the
largest tumor (cm) and the number of tumors] and were treated with Hx (n=23) or
RFA (n=35); their clinical features, complications and prognosis were assessed.
The frequency of hepatitis C virus was higher in the RFA group compared with that
in the Hx group (P=0.002), whereas there were no differences between the groups
with regard to the average time from the first HD (P=0.953), tumor-nodes
metastasis (TNM) stage (Union for International Cancer Control 7th edition)
(P=0.588), TNM stage (Liver Cancer Study Group of Japan 5th edition) (P=0.095),
Child-Pugh classification (P=0.094), and Japan Integrated Scoring system
(P=0.489). There were no significant differences in overall survival (OS) and
disease-free survival (DFS) rates between the Hx and RFA groups [1-, 3- and 5
year OS rates: 81.7, 55.6 and 43.3% vs. 89.9, 67.1 and 56.3%, respectively
(P=0.454); 1-, 3- and 5-year DFS rates: 71.1, 30.5 and 18.3% vs. 63.8, 31.6 and
21.1%, respectively (P=0.911)] Complications were observed in 4 patients (11.4%)
in the RFA group (2 with subcapsular hemorrhage, 1 with intraperitoneal bleeding
and 1 with tardive intrahepatic hematoma) and in 4 patients (17.4%) in the Hx
group (2 with postoperative infection, 1 with liver failure and 1 with pleural
effusion) (P=0.700). In conclusion, Hx and RFA have a similar therapeutic
efficacy in HD patients with naive HCC who fulfilled the up-to-7 criteria.
PMID- 28413652
TI - Bilateral blindness with secondary retinitis pigmentosa following postoperative
docetaxel and platinum combination chemotherapy in primary small-cell carcinoma
of the endometrium: An unusual case report and review of the literature.
AB - Ocular toxicity is an uncommon complication of cytotoxic chemotherapy. Bilateral
blindness with secondary retinitis pigmentosa (RP) following docetaxel and
platinum combination chemotherapy at the recommended dose is extremely rare. The
present study reports a case of advanced small-cell carcinoma (SCC) of the
endometrium in a patient with diabetes mellitus type 2. The patient suffered from
RP with a sharp decline in vision after the fourth course of postoperative
docetaxel and platinum combination chemotherapy. Unfortunately, the patient
developed bilateral blindness after another course of chemotherapy at a reduced
dose. No tumor recurrence was observed during the 33 months of follow-up. A total
of 35 cases of docetaxel- and/or platinum-induced retinal toxicity were found in
the English literature and reviewed. The ischemic and electrophysiological
hypotheses may have been implicated in the pathogenesis of ocular toxicity in the
present case, particularly with the history of diabetes. Understanding the ocular
side effects of this combination chemotherapy may assist gynecological
oncologists and ophthalmologists with early recognition and timely intervention
before blindness is established.
PMID- 28413651
TI - High radiofrequency radiation at Stockholm Old Town: An exposimeter study
including the Royal Castle, Supreme Court, three major squares and the Swedish
Parliament.
AB - Exposure to radiofrequency (RF) radiation was classified as a possible human
carcinogen, Group 2B, by the International Agency for Research on Cancer at WHO
in 2011. The exposure pattern is changing due to the rapid development of
technology. Outdoor RF radiation level was measured during five tours in
Stockholm Old Town in April, 2016 using the EME Spy 200 exposimeter with 20
predefined frequencies. The results were based on 10,437 samples in total. The
mean level of the total RF radiation was 4,293 uW/m2 (0.4293 uW/cm2). The highest
mean levels were obtained for global system for mobile communications (GSM) +
universal mobile telecommunications system (UMTS) 900 downlink and long-term
evolution (LTE) 2600 downlink (1,558 and 1,265 uW/m2, respectively). The town
squares displayed highest total mean levels, with the example of Jarntorget
square with 24,277 uW/m2 (min 257, max 173,302 uW/m2). These results were in
large contrast to areas with lowest total exposure, such as the Supreme Court,
with a mean level of 404 uW/m2 (min 20.4, max 4,088 uW/m2). In addition,
measurements in the streets surrounding the Royal Castle were lower than the
total for the Old Town, with a mean of 756 uW/m2 (min 0.3, max 50,967 uW/m2). The
BioInitiative 2012 Report defined the scientific benchmark for possible health
risks as 30-60 uW/m2. Our results of outdoor RF radiation exposure at Stockholm
Old Town are significantly above that level. The mean exposure level at
Jarntorget square was 405-fold higher than 60 uW/m2. Our results were below the
reference level on 10,000,000 uW/m2 established by the International Commission
on Non-Ionizing Radiation Protection (ICNIRP), which, however, are less credible,
as they do not take non-thermal effects into consideration and are not based on
sound scientific evaluation. Our highest measured mean level at Jarntorget was
0.24% of the ICNIRP level. A number of studies have found adverse, non-thermal
(no measurable temperature increase) health effects far below the ICNIRP
guidelines.
PMID- 28413653
TI - A novel option for preoperative endoscopic marking with India ink in totally
laparoscopic distal gastrectomy for gastric cancer: A useful technique
considering the morphological characteristics of the stomach.
AB - In totally laparoscopic distal gastrectomy (TLDG) for gastric cancer, accurately
determining the proximal resection line may be difficult. This is because
identifying the lesion intracorporeally is impossible, due to the lack of tactile
sense, and, in addition, unlike the intestine, the most proximal site of the
lesion is often different from the main site due to the distorted shape of the
stomach. The aim of this study was to introduce a novel method of preoperative
endoscopic marking with India ink, taking into consideration the morphological
characteristics of the stomach. Between July, 2013 and April, 2016, 20 patients
who underwent TLDG were enrolled in this study. Within the 3 days preceding the
operation, after identifying the most proximal site of the lesion on the
overlooking image of an endoscope, India ink was injected into the spot on the
oral side of this site. The stomach was transected along the proximal border of
the marked area. In all cases, the marked sites were localized and clearly
identified during the operation, and the proximal resection margins were found to
be negative on postoperative pathological examination. The mean length of the
proximal margin was 46.0+/-14.0 mm. In conclusion, this preoperative endoscopic
marking method may be useful in TLDG for gastric cancer.
PMID- 28413654
TI - Hepatic perivascular epithelioid cell neoplasm: A clinical and pathological
experience in diagnosis and treatment.
AB - Hepatic perivascular epithelioid cell neoplasm (PEComa) is a rare type of
neoplasm derived from mesenchymal tumors that is often misdiagnosed as
hepatocellular carcinoma (HCC), hepatic hemangioma or other liver malignancies.
The clinical and histological characteristics of PEComa have yet to be fully
documented. To optimize the diagnosis and treatment of the disease, a
retrospective analysis was performed to investigate the clinicopathological
characteristics of 7 patients diagnosed with hepatic PEComa in the Sun Yat-Sen
Memorial Hospital between January 2004 and December 2015. Briefly, all the
patients lacked specific symptoms, and a serological examination provided no
further useful information. Additionally, non-specific imaging manifestations
were observed. Microscopically, detection of epithelioid or spindle-shaped cells
with adipocytes was suggestive of the disease, and an analysis of biomarkers,
including the monoclonal antibody HMB-45, the melanocytic differentiation marker,
Melan-A, and smooth muscle alpha-actin (SMA), helped to confirm the diagnosis.
Regarding the treatment, 6 patients (85.7%) received surgical resection
procedures, and 1 patient (14.3%) was admitted for tumor arterial embolization
and percutaneous microwave coagulation therapy. After a follow-up period of 12-20
months, no recurrence was observed. Taken together, hepatic PEComa should be
suspended in patients with a liver tumor with asymptomatic manifestation and
normal serological test results. In imaging studies, hepatic PEComa was able to
mimic HCC, hepatic hemangioma and metastatic tumor, although the mass did not
invade the adjacent organs and vessel. The definitive diagnosis was made on the
basis of the typical morphological features and notable markers of the tumor
tissue. It is recommended that patients with PEComa in a benign pattern deserve
serial imaging follow-up, but surgery is indicated in patients suffering from
large tumors (>5 cm), or progressive enlargement or malignant tendency.
PMID- 28413655
TI - Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer.
AB - The enzyme cyclooxygenase 2 (COX-2) is known to be involved in tumorigenesis and
metastasis in certain types of cancer. Nevertheless, the prognostic value of COX
2 overexpression and its polymorphisms in patients with non-small cell lung
cancer (NSCLC) have yet to be fully elucidated. The aim of the present study was
to investigate the association between the three most commonly studied COX-2 gene
polymorphisms (-1195 G/A, -765 G/C and 8473 T/C) with COX-2 expression and lung
cancer risk in a Brazilian cohort. In the present hospital based, case-control
retrospective study, 104 patients with NSCLC and 202 cancer free control subjects
were genotyped for -1195 G/A, -765 G/C and 8473 T/C polymorphisms using allelic
discrimination with a reverse transcription quantitative polymerase chain
reaction method. COX-2 mRNA expression was analyzed in surgically resected tumors
from 34 patients with NSCLC. The results revealed that COX-2 expression levels
were higher in tumor tissue compared with normal lung tissue. However, this
overexpression of COX-2 was not associated with the patient outcome, and
furthermore, none of the analyzed polymorphisms were associated with the risk of
developing lung cancer, COX-2 overexpression, or the overall survival of the
patients with NSCLC. Taken together, the findings described in the present study
do not support a major role for COX-2 polymorphisms and COX-2 overexpression in
lung carcinogenesis within the Brazilian population.
PMID- 28413656
TI - Effect of Ki-67 assessment in the distribution of breast cancer subtypes:
Evaluation in a cohort of Latin American patients.
AB - Breast cancer (BC) is a heterogeneous disease composed of four main subtypes with
distinct clinical and epidemiological features. Although several reports have
described the distribution of BC subtypes in Latin America, the majority of them
have not included the cellular marker, Ki-67, in the immunohistochemical (IHC)
panel. The aim of the present study was to describe the distribution of BC
subtypes in a cohort of Latin American women using an IHC panel with Ki-67. A
prospective cohort of 580 patients in three centers of Peru (the Hospital
Nacional Edgardo Rebagliatti Martins, the Hospital Nacional Guillermo Almenara
Irigoyen, the Hospital Nacional Alberto Sabogal, Lima) and one in Uruguay
(Instituto Nacional del Cancer, Montevideo) were evaluated. BC phenotypes were
classified according to an IHC panel: Estrogen receptor (ER), progesterone
receptor (PgR), HER2 and Ki-67. Silver in situ hybridization was used when the
HER2 status, as determined by IHC, was equivocal. The associations between the BC
phenotypes and their clinicopathological features were evaluated. ER was positive
in 65% of the cases (n=377), and PgR in 50% (n=203). In total, 79.1% (n=459) were
HER2-negative, 19.8% (n=115) were HER2-positive and 1% (n=6) had an equivocal
status. With respect to Ki-67, 44.7% of the patients exhibited staining in >14%
of the tumor cells (n=259). The distribution of subtypes was as follows: Luminal
A, 31.9% (n=183); luminal B, 35% (n=201); HER2, 12.1% (n=70); and triple
negative, 20.9% (n=120). When Ki-67 was not included in the panel, the frequency
of luminal A was 41.1% and luminal B, 25.8% (9.2% of the cases were
misclassified). Ki-67 was most highly expressed in triple-negative and HER2
tumors. Inclusion of Ki-67 in the IHC panel to assign subtypes revealed a higher
frequency of luminal B tumors than was reported previously for Latin American
women with BC, whereas the distribution of triple-negative and HER2 tumors were
similar to that previously reported. In conclusion, these results demonstrated
that excluding Ki-67 from the panel of IHC markers may lead to an underestimation
of the rates of luminal B tumors.
PMID- 28413657
TI - A feasibility study of bevacizumab and vinorelbine in patients with previously
treated advanced non-squamous non-small-cell lung cancer.
AB - The aim of this prospective study was to evaluate the efficacy and feasibility of
bevacizumab combined with vinorelbine therapy in patients with previously treated
non-squamous non-small-cell lung cancer (nonSq-NSCLC). Patients who had received
at least one prior chemotherapy course were eligible for this study. The patients
were treated with vinorelbine (25 mg/kg on days 1 and 8) and bevacizumab (15
mg/kg on day 1), which was repeated every 3 weeks until the development of
progressive disease or unacceptable toxicity. Between June, 2011 and January,
2013, 15 patients were enrolled. The response and disease control rates were 26.7
and 73.3%, respectively. The median progression-free survival was 2.1 months and
the median overall survival was 34.1 months. Grade 3-4 phlebitis occurred in 3
patients. Therefore, the combination of vinorelbine and bevacizumab was found to
be effective in patients with previously treated nonSq-NSCLC, but physicians must
be aware of the risk of phlebitis associated with this regimen.
PMID- 28413658
TI - Subcutaneous metastasis arising from gastric cancer: A case report.
AB - A 59-year-old man was referred to the Kochi Medical School Hospital due to left
shoulder pain. Physical examination revealed a nodular, painful mass lesion in
the subcutaneous tissue of the right chest wall, with a diameter of ~2 cm.
Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower gastric
body near the lesser curvature, and biopsy specimens of the gastric and humeral
lesions revealed poorly differentiated adenocarcinoma. Abdominal computed
tomography revealed multiple low-density lesions in the liver and a well-defined,
2.2-cm mass in the subcutaneous tissue of the right chest wall. The diagnosis was
advanced gastric cancer with metastases to the liver, bone and skin, and systemic
chemotherapy with radiotherapy for the bone metastasis was recommended. The
patient also underwent distal gastrectomy to control bleeding from the primary
gastric cancer lesion due to unresolved anemia, not improving by blood
transfusion, and a low hemoglobin level. The subcutaneous tumor in the right
chest wall was resected at the same time, to alleviate the pain caused by the
mass. Macroscopic examination of the resected specimen revealed a well
circumscribed, solid tumor, measuring 2.2*2.1 cm, with a firm consistency.
Microscopic examination showed infiltration of poorly differentiated
adenocarcinoma cells into the subcutaneous tissue. Subcutaneous metastasis from
gastric cancer is a rare manifestation, with a reported incidence of 0.8-1.0%.
Cutaneous metastasis of cancer generally appears late in the course of the
disease. Surgical resection of metastatic skin tumors is occasionally undertaken
as palliative treatment to improve the patient's quality of life by controlling
severe symptoms, including pain and hemorrhage.
PMID- 28413659
TI - Patient gender as a factor associated with lymph node metastasis in T1 colorectal
cancer: A systematic review and meta-analysis.
AB - Approximately 10% of patients with T1 colorectal cancer have lymph node
metastases (LNM), requiring node dissection along with surgical resection.
Patient gender was recently reported to affect the occurrence of LNM. The aim of
the present study was to assess whether patient gender was predictive of LNM in
T1 colorectal cancer. Public databases, including PubMed, EMBASE and the Cochrane
Central Register of Controlled Trials were searched, using key terms related to
'T1 colorectal cancer' and 'lymph node'. All relevant studies reporting the
adjusted odds ratio or risk ratio of LNM in relation to patient gender were
included. The quality of the studies was classified according to the Quality in
Prognostic Studies tool. A random-effects model was used and the quality of the
evidence was evaluated using the Grading of Recommendations Assessment,
Development and Evaluation approach. The initial database search identified 2,492
publications; of those, 36 studies reported unadjusted results. Of the 36
studies, 4 reported adjusted results and fulfilled the inclusion criteria for
this meta-analysis: 3 studies were graded as having a moderate risk of bias, and
1 had a low risk of bias. The present meta-analysis demonstrated that female
gender was associated with increased risk of LNM (risk ratio=2.45, 95% confidence
interval: 1.03-3.88). The I2 statistic was 0.901, classified as very low (+OOO)
and was downgraded by the risk of bias, inconsistency and publication bias. In
conclusion, female gender was found to be correlated with LNM in patients with T1
colorectal cancer.
PMID- 28413660
TI - Dramatic intracranial response to osimertinib in a poor performance status
patient with lung adenocarcinoma harboring the epidermal growth factor receptor
T790M mutation: A case report.
AB - We herein report a case of dramatic intracranial response to osimertinib in a
poor performance status patient with lung adenocarcinoma harboring the epidermal
growth factor receptor (EGFR) T790M mutation encoded in exon 20. The patient was
a 59-year-old woman with EGFR exon 19 deletion-positive lung adenocarcinoma, who
relapsed with multiple brain metastases. Computed tomography-guided biopsy of the
left pleural tumor revealed adenocarcinoma harboring an EGFR exon 19 deletion and
an EGFR T790M mutation encoded in exon 20. The patient was treated with
osimertinib, a third-generation EGFR tyrosine kinase inhibitor. Two days after
treatment initiation, the patient displayed profound disturbance of
consciousness, possibly due to carcinomatous meningitis, and treatment had to be
discontinued due to difficulty in taking osimertinib. However, the patient
gradually started to recover consciousness and, after 3 days, she was again able
to take osimertinib. One month after the initiation of osimertinib treatment,
magnetic resonance imaging revealed an apparent reduction in brain metastases.
The patient is currently under continued treatment with osimertinib. At the last
follow-up (February, 2017) she exhibited partial response to the treatment.
PMID- 28413661
TI - Non-alcoholic fatty liver disease fibrosis score predicts hematological toxicity
of chemotherapy including irinotecan for colorectal cancer.
AB - Liver dysfunction that may affect drug metabolism is a major concern in patients
treated with chemotherapy. Thus, assessment of the degree of liver dysfunction is
crucial for predicting the adverse events of chemotherapy. The non-alcoholic
fatty liver disease fibrosis score (NFS) is a non-invasive clinical scoring
system constructed from routine clinical and laboratory variables. The aim of
this study was to evaluate whether NFS was useful for predicting the adverse
events of chemotherapy including irinotecan (CPT-11) for colorectal cancer.
Between January, 2007 and May, 2013, a total of 87 patients with
unresectable/recurrent colorectal cancer who received first-line chemotherapy
including CPT-11 were reviewed. Demographic variables, including pretreatment
NFS, were retrospectively collected from medical records. The primary outcome was
the association between pretreatment NFS and adverse events, such as
hematological and non-hematological toxicity, of chemotherapy including CPT-11.
The median pretreatment NFS was 1.302 (range, 5.158-2.620). Pretreatment NFS was
an independent risk factor for hematological toxicity in a multivariate analysis
(coefficient=0.932, 95% CI: 0.083-1.781; P=0.031). Receiver operating
characteristic curve analysis identified 0.347 as the optimal cut-off value
associated with hematological toxicity. Using this cut-off, high NFS was found to
be a significant risk factor for hematological toxicity (coefficient=2.019, 95%
CI: 0.239-3.798, P=0.026), but not for non-hematological toxicity (P=0.546).
Therefore, based on these results, NFS appears to be a significant predictor of
hematological adverse events in chemotherapy including CPT-11 for colorectal
cancer and it is a non-invasive, useful tool that may be used for determining
regimens or doses of chemotherapy including CPT-11.
PMID- 28413662
TI - Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and
trastuzumab in women with human epidermal growth factor receptor 2-overexpressing
breast cancer.
AB - Although the concurrent use of anthracycline-containing chemotherapy and taxane
with trastuzumab are considered the treatment of choice for the primary systemic
therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early
breast cancer, non-anthracycline regimens, such as concurrent administration of
docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a
previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound
paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a
favorable safety profile compared with standard paclitaxel for metastatic breast
cancer patients in another phase III study. Based on these results, a phase I
study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was
planned, in order to estimate its efficacy and safety for HER2-overexpressing
locally advanced breast cancer. The present study was designed to determine the
dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this
combination treatment in women with HER2-overexpressing locally advanced breast
cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose
was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with
carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A
total of 6 patients were enrolled. Although no DLT was observed during the first
cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia
and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I
study, although no patients experienced DLTs, this regimen was associated with
severe hematological toxicities and it was not well tolerated. However,
considering the high efficacy and lower risk of cardiotoxicity and secondary
carcinogenesis with taxane, platinum and trastuzumab combination therapy, further
evaluation of another regimen including weekly administration or a more accurate
dose setting should be conducted.
PMID- 28413663
TI - Breast implant-associated anaplastic large-cell lymphoma and the role of
brentuximab vedotin (SGN-35) therapy: A case report and review of the literature.
AB - Breast implant-associated (BIA) anaplastic large-cell lymphoma (ALCL) is a rare
disease, comprising a small percentage of all non-Hodgkin lymphomas (NHLs),
reportedly 2-3%. There is currently no established standard approach to the
treatment of BIA ALCL. The first case on the development of ALCL in the presence
of a breast implant was reported in 1997 and the association was first identified
by the Food and Drug Administration in 2011. We herein describe a case of BIA
ALCL in a patient with a previous history of breast cancer and breast
reconstruction who presented with hardening of her breast implant. The patient
underwent capsulectomy and the findings of the pathological examination were
consistent with ALCL. The patient completed three cycles of combination
chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and
prednisone (CHOP regimen) followed by radiation consolidation therapy, and has
maintained a complete remission ever since. The aim of the present study was to
review the treatment options for BIA ALCL and suggest an investigation of the
CD30-directed antibody-drug conjugate, brentuximab vedotin, as a potential
treatment option for BIA ALCL.
PMID- 28413664
TI - Extranodal natural killer/T-cell lymphoma presenting as cavernous sinus syndrome.
AB - Extranodal natural killer (NK)/T-cell lymphomas are rare, highly aggressive
tumors of the central nervous system (CNS) that commonly affect the nasal cavity
or paranasal sinuses. NK/T-cell lymphomas are associated with a poor prognosis,
as they exhibit a wide range of unique clinical presentations and neuroimaging
findings that are currently difficult to detect. Pathological examination is
considered to be more reliable for defining the pathological entity of NK/T-cell
lymphoma. Early testing for fluorodeoxyglucose (FDG)-positron emission tomography
combined with computed tomography may improve the evaluation of lymphomas, which
have been known to display avid 18FDG uptake. The authors herein report a case of
NK/T-cell lymphoma presenting with cavernous sinus syndrome involving the CNS via
direct extension from the nose. NK/T-cell lymphomas are very aggressive, with an
unfavorable clinical outcome, and the optimal therapy has not yet been clearly
defined.
PMID- 28413665
TI - Hepatic inflammatory pseudotumour-like follicular dendritic cell tumor: A case
report.
AB - Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) tumor
is a rare neoplasm. We herein report the case of 19-year-old female patient with
an IPT-like FDC tumor and summarize 24 cases of hepatic FDC tumors previously
reported in the English literature. The patient presented with complaints of
abdominal discomfort, without significant laboratory abnormalities, and underwent
surgical removal of a hepatic tumor. The resected tumor was 6 cm in the longest
diameter and the tumor cells were positive for CD21, CD35 and Epstein-Barr virus
(EBV). The postoperative course was uneventful and there have been no metastases
or recurrence during 1 year of follow-up. The majority of the cases of hepatic
IPT-like FDC tumors have a female predominance and exhibit an association with
EBV infection. Their clinical manifestations and image findings are usually non
specific and the diagnosis of this disease mainly relies on pathology.
PMID- 28413666
TI - Renal cell carcinoma presenting as a simple renal cyst: A case report.
AB - Cases of renal cell carcinoma (RCC) presenting as a simple cyst are extremely
rare. We herein report the case of a patient with RCC diagnosed as a simple renal
cyst preoperatively. A 39-year-old female patient presented with abdominal pain
for 3 months. Ultrasonography and contrast-enhanced computed tomography revealed
a simple cyst in the left kidney. The patient underwent laparoscopic
decortication of the renal cyst. Biochemical analysis of the cystic fluid
revealed unusually low levels of potassium, sodium, calcium and glucose, and the
histological examination of the floor of the cyst indicated malignancy.
Laparoscopic nephrectomy was performed 20 days later and the pathological
examination confirmed the diagnosis of RCC of the clear cell type. At the 2-year
follow-up, the patient remained well and recurrence-free on imaging. The aim of
the present study was to emphasize the importance of recognizing that RCC may
occur in what appears to be a simple renal cyst based on imaging results.
Biochemical analysis of the cystic fluid may help identify the presence of
malignancy.
PMID- 28413667
TI - Paraganglioma of the bladder in a kidney transplant recipient: A case report.
AB - Renal transplantation has been associated with a significantly increased risk of
developing cancer, including bladder neoplasia, with urothelial carcinoma being
the most frequent type of bladder cancer. Bladder paraganglioma, also referred to
as extra-adrenal pheochromocytoma, is a rare but severe condition that may cause
a severe hypertensive crisis during handling and mobilization of the tumor. We
herein present the case of a 67-year-old kidney transplant recipient with a
bladder polyp consistent with paraganglioma of the bladder. During bladder polyp
resection, the patient developed severe hypertension, which resolved with
appropriate treatment. The histological analysis of the resected bladder polyp
was consistent with extra-adrenal pheochromocytoma, or paraganglioma, and the
patient finally underwent partial cystectomy, with no reported postoperative
recurrence. To the best of our knowledge, this is the first report of a case of
paraganglioma of the bladder in a kidney tranplant recipient. Total or partial
bladder cystectomy is considered to be an effective treatment for this type of
bladder tumor. Screening for mutations of the succinate dehydrogenase subunit B
gene may also be recommended.
PMID- 28413668
TI - PALB2 mutation in a woman with bilateral breast cancer: A case report.
AB - Partner and localizer of breast cancer 2 (PALB2) was identified as a moderate
risk gene of breast and pancreas cancer. The present authors previously reported
that no PALB2 germline mutations with a deleterious frameshift or stop codons
were identified in 155 Japanese patients with breast and/or ovarian cancer who
were estimated to be at risk of hereditary cancer, according to the National
Comprehensive Cancer Network (NCCN) criteria. In the present study, one patient
with a deleterious mutation of PALB2 (c. 2834+2 T>C) has been identified from a
study of an additional 128 cases. Therefore, the prevalence of PALB2 among
Japanese patients is now estimated to be 0.35% (1/283). The proband was a 63-year
old woman with bilateral breast cancer, although she had experienced no other
cancers. The proband had two elder sisters, the eldest of whom died from
pancreatic cancer at 60 years of age. The proband's 40-year-old daughter was
affected, but did not show any malignancies. There are only a few reports
concerning PALB2 mutations in Japan. To the best of our knowledge, this is the
first case study to reveal the significance of DNA-repair genes in the
development of malignancies in Japanese patients with breast cancer.
PMID- 28413669
TI - Gemcitabine-based chemotherapy in colon squamous cell carcinoma: A case report
and literature review.
AB - Squamous cell carcinoma (SCC) originating from the colon is rare. In terms of its
clinicopathological characteristics, this type of cancer has been reported to be
more aggressive and have a worse prognosis compared with adenocarcinoma. We
herein present a successful therapeutic approach applying neoadjuvant and
adjuvant gemcitabine-based chemotherapy in a patient with colon SCC. A 58-year
old male patient received two cycles of neoadjuvant chemotherapy with a regimen
including gemcitabine, oxaliplatin and capecitabine, followed by radical excision
and six cycles of adjuvant chemotherapy. Contrast-enhanced computed tomography
and serum tumor markers were used for reassessment and evaluation was based on
the World Health Organization criteria. Following neoadjuvant chemotherapy, the
mass had shrunk and the patient was classed as having stable disease. Surgery and
adjuvant chemotherapy were then performed and the patient had achieved a
progression-free survival of 10 months when this report was submitted. Therefore,
gemcitabine may be a treatment option for colon SCC in the neoadjuvant and/or
adjuvant chemotherapy setting.
PMID- 28413670
TI - Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma.
AB - High Glasgow Prognostic Score (GPS) has been associated with poor prognosis in
patients with lung, ovarian, colorectal and renal cancer, as well as
hepatocellular carcinoma. The aim of this study was to investigate the prognostic
value of GPS in patients with intrahepatic cholangiocarcinoma (ICC) undergoing
partial hepatectomy. A total of 72 patients with pathologically confirmed ICC
were classified according to their GPS scores assigned based on the preoperative
levels of C-reactive protein (CRP) and albumin. Their clinicopathological data
were retrospectively assessed using univariate and multivariate analysis to
determine their association with overall survival and recurrence. High GPS scores
in ICC patients were associated with preoperative levels of CRP (P<0.001) and
albumin (P<0.001), frequency of ascites accumulation (P=0.035), lymph node
metastasis (P=0.002) and tumour size (P=0.005). On univariate analysis,
preoperative levels of CRP (P<0.001), albumin (P=0.016) and carbohydrate antigen
19-9 (P=0.038), hepatitis B virus (HBV) positivity (P=0.009), occurrence of lymph
node metastasis (P=0.001), Child-Pugh class B (P=0.013) and high tumour-node
metastasis (TNM) stage (P=0.002) were found to be associated with the 1- and 3
year overall survival. Multivariate analysis suggested that GPS score (HR=2.037,
95% CI: 1.092-3.799, P=0.025), TNM classification (HR=2.000, 95% CI: 1.188-3.367,
P=0.009) and HBV positivity (HR=0.559 95% CI: 0.328-0.953, P=0.032) were
independently associated with patient survival. High GPS scores also predicted
ICC recurrence. In conclusion, our results demonstrated that GPS may serve as an
independent marker of prognosis in patients with ICC following partial
hepatectomy.
PMID- 28413671
TI - Paraneoplastic limbic encephalitis in a patient with extensive disease small-cell
lung cancer.
AB - Paraneoplastic limbic encephalitis (PLE) is a rare disorder infrequently
accompanying malignancy, coexisting in ~50% of the cases with small-cell lung
cancer (SCLC). The pathomechanism of PLE is considered to be immune-mediated,
with production of specific anti-Hu antibodies and activation of T-cells directed
against onconeural antigens present on both tumor cells and neurons. We herein
report the case of a 50-year-old male patient who, prior to being diagnosed with
SCLC, presented with typical symptoms of PLE (seizures, subacute cognitive
dysfunction with severe memory impairment, anxiety and hallucinations). The
initial brain magnetic resonance imaging examination revealed mild enlargement
and hyperintensity of the hippocampal gyri bilaterally, with narrowed temporal
horns of the lateral ventricles; the findings of the cerebrospinal fluid
examination were compatible with the diagnosis of lymphocytic meningitis. Due to
the suspected infectious origin of the disease, treatment with acyclovir and
antibiotics was initially applied. However, following subsequent diagnosis of the
underlying SCLC and the presence of antineuronal anti-Hu antibodies in the
patient's serum, the diagnosis of PLE accompanying extensive-disease (ED) SCLC
was confirmed. In addition to the standard cytotoxic therapy, throughout the
course of his disease the patient also continued treatment with valproic acid
(VPA) as prophylaxis for the initial seizures. VPA is known to be a potent
histone deacetylase inhibitor that may reverse epigenetic changes in tumor cells
and potentially improve the outcome of cancer patients. The patient succumbed to
the disease 25 months after the diagnosis of malignancy; such a long course is
observed in only ~5% of patients with ED SCLC. Therefore, it was hypothesized
that the accompanying paraneoplasia and treatment with VPA may have improved the
outcome in this patient.
PMID- 28413672
TI - Whole-body magnetic resonance imaging in the diagnosis and follow-up of
multicentric infantile myofibromatosis: A case report.
AB - Myofibromatosis is an uncommon disorder of infancy, characterized by
proliferation of myofibroblasts in solitary or multiple nodules. The clinical
characteristics depend on the involved sites: Myofibromatosis may develop as a
musculoskeletal form, with non-painful swellings and eventual mass effect
symptoms, or as a generalized form with visceral involvement and organ failure.
Prognosis and therapy vary between the abovementioned patterns. When there is no
visceral involvement, the tumors may regress spontaneously; however, the visceral
form may represent a lifethreatening condition with poor outcome and it requires
aggressive management. Imaging assessment of disease spread is mandatory to
determine diagnosis, prognosis and therapy. Due to the young age of the patients,
a radiation-free evaluation is recommended. We herein describe a case of
musculoskeletal myofibromatosis diagnosed in a 3-month-old male infant,
investigated by serial wholebody magnetic resonance imaging (MRI) examination.
The histological analysis and MRI characteristics enabled a correct diagnosis and
organ involvement assessment with no radiation exposure. Moreover, whole-body MRI
sequences provided a detailed evaluation of the disease within a short time
frame, reducing the time of sedation, which is required to perform MRI in very
young patients. Therefore, whole-body MRI was found to be accurate and safe in
the diagnosis and follow-up of multicentric infantile myofibromatosis.
PMID- 28413673
TI - Survival of patients with pancreatic cancer treated with varied modalities: A
single-centre study.
AB - The present retrospective chart review examined the overall survival (OS) of
patients with pancreatic ductal adenocarcinoma based on the disease stage in a
sample of 296 patients with pancreatic cancer. Secondary outcome measurements
included OS in chemotherapy vs. supportive treatment groups among metastatic
patients, OS based on response to chemotherapy among metastatic patients, and OS
and disease free survival (DFS) in surgically resected disease with vs. without
adjuvant therapy. Data were analyzed using Kaplan-Meier and multivariate cox
regression analyses based on a 95% confidence interval (CI) or an alpha-value of
0.05. OS was significantly different based on the disease stage, with 3.63 (95%
CI, 2.84-4.43), 6.57 (95% CI, 4.06-9.08) and 15.57 (95% CI, 11.79-19.35) months
in the advanced, locally advanced, and localized disease groups, respectively. OS
was higher in metastatic-stage patients who received chemotherapy [6.07 months
(95% CI, 4.75-7.39)] compared with those who received supportive therapy alone
[2.50 months (95% CI, 2.16-2.84; P<.001)]. Metastatic-stage patients with partial
or stable response to chemotherapy had higher OS [10.53 months (95% CI, 6.35
14.72)] in comparison with those with progression [6.33 months (95% CI, 5.79
6.88)] or an undocumented response [3.30 months (95% CI, 1.76-4.84; P<0.001)]. In
patients who underwent surgical resection of localized disease, adjuvant therapy
increased the adjusted OS and DFS as compared with surgical excision alone
(P=0.013; 95% CI, 0.278-0.862). Positive margins reduced OS [hazard ratio (HR)
2.670; 95% CI, 1.467-4.860]. The present single-site study has demonstrated that
OS may markedly differ on the basis of the disease status at the time of
diagnosis. Metastatic-stage patients with stable or partial response to
chemotherapy had an increased OS, as did surgical patients with localized disease
who received adjuvant treatment, after adjusting for margin status.
PMID- 28413674
TI - Spontaneous tumor lysis syndrome in a patient with metastatic prostate cancer.
AB - Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, with most
cases occurring in hematological malignancies following the initiation of
treatment. However, on rare occasions, TLS may occur in solid tumors as well. In
the present case study, the case is reported of a 56-year-old African-American
man who presented with a recent diagnosis of prostate cancer, abdominal pain,
elevated transaminases, renal insufficiency, hyperkalemia, and hyperuricemia,
consistent with spontaneous TLS in the setting of metastatic prostate cancer. A
computed tomography scan of the patient's abdomen demonstrated diffuse metastatic
tumor burden. Following treatment with allopurinol, rasburicase, and initiation
of anti-androgen therapy for the prostate cancer, the patient's TLS laboratory
results normalized, however, his renal functions continued to decline. TLS is
rare in solid tumors, and particularly rare in prostate cancer, with only six
other case reports of the syndrome occurring to the best of our knowledge. This
case report highlights the need for early recognition of TLS, even in cases that
are not typically associated with the syndrome, as prompt diagnosis will affect
early management and may be able to prevent or minimize complications.
PMID- 28413675
TI - Primary mesenteric adenocarcinoma covered by abscess of the mesocolon and
intestinal obstruction: A case report.
AB - Primary mesenteric adenocarcinoma (PMA) is a rare malignant disease. A case of
PMA that was covered by an abscess of the mesocolon and intestinal obstruction is
reported in the present study. As the onset site of PMA is often obscured or
hidden, there may be no clinical symptoms in the early stage. At the advanced
stage, the tumor size is large enough to induce intestinal obstruction,
perforation, bleeding, volvulus and other clinical symptoms in the majority of
patients. Computed tomography scans, ultrasound and other auxiliary examinations
are not sufficiently accurate for diagnosing PMA with non-specific
characteristics in the majority of cases, causing certain difficulties in the pre
operative diagnosis of PMA, which easily lead to misdiagnosis. The main effective
treatment of PMA is surgical resection as early as possible. Thus, when a patient
is suspected of having malignancies, and gastrointestinal cancer and other
malignancies of the digestive organs may be excluded, the possibility of PMA
should be considered.
PMID- 28413676
TI - Expression patterns of CD168 correlate with the stage and grade of squamous cell
carcinoma of head and neck.
AB - The receptor for hyaluronan-mediated motility CD168 is associated with the
processes of oncogenesis and metastasis. The objective of the present study was
to determine the possible association between the expression and distribution of
CD168 and the tumor stage of head-and-neck squamous cell carcinoma (SCC).
Formalin-fixed and paraffin-embedded tumor samples obtained from 100 patients
during primary resection of SCC from the oral cavity, oropharynx, hypopharynx or
larynx were included in the present study. The patients were divided into two
risk groups: Low risk, representing the early stage of completely resected SCCs
with good-to-moderate differentiation, and the high-risk group, representing the
advanced stage SCCs with positive resection margins, vascular invasion or
locoregional metastasis. All specimens were stained with a monoclonal antibody
against CD168. Percentage and staining intensity of CD168-positive cells were
scored, and their spatial distribution within the tumor nests was noted. The
results obtained were correlated with the tumor stage. The quantification of
CD168 expression revealed significant differences between the two risk groups (t
test, P=0.002), with higher scores in tumors resected from the high-risk SSC
group compared with those from the low-risk group. In addition, in the high-risk
group, the CD168-positive cells were present predominantly in the periphery
(70.4%) of tumor nests, whereas in the low-risk group, only 56.6% were located
there; however, this trend did not reach the level of statistical significance.
Taken together, the results from the present study suggested that CD168
expression patterns could potentially be used as a predictor of tumor
aggressiveness, and therefore they may be a prognostic factor in head-and-neck
SCC.
PMID- 28413677
TI - Management of afatinib-induced stomatitis.
AB - Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy
and, thus, may affect control of the primary disease. Stomatitis may also
increase the risk of local and systemic infection and significantly affects the
quality of life and the cost of care. The present study was conducted to evaluate
the efficacy of two traditional herbal medicines in controlling treatment-induced
stomatitis in a small cohort of lung cancer patients treated with afatinib. All
patients who were treated with afatinib for epidermal growth factor receptor
(EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March,
2016, were included in this study. During the study period, a total of 14 NSCLC
patients were treated with afatinib, an EGFR-tyrosine kinase inhibitor (TKI). Two
patients already had stomatitis at the time of initiation of afatinib therapy;
among the remaining 12 NSCLC patients, 2 (16.7%) developed stomatitis. All the
lesions in the 4 patients who developed stomatitis were completely alleviated
after 2 weeks of therapy with Aznol mouthwash, a chamomile extract with anti
inflammatory effects, and Hangeshashinto, a traditional herbal (Kampo) medicine.
Afatinib therapy was re-initiated, but none of the patients developed stomatitis
thereafter. To the best of our knowledge, this is the first report evaluating
oral care and management of stomatitis. This type of care and treatment may
reduce the incidence of complications associated with EGFR-TKI therapy.
PMID- 28413678
TI - The significance of multi-line chemotherapy for advanced gastric cancer: A
retrospective analysis.
AB - Palliative chemotherapy is known to benefit patients with advanced gastric cancer
by palliating symptoms and improving survival. The aim of the present study was
to evaluate the efficacy and toxicity of chemotherapy regimens that are commonly
used in patients with advanced or recurrent gastric cancer. Patients with
advanced or recurrent gastric cancer who were treated by at least two
chemotherapy regimens between May 2006 and July 2014 at Zhejiang Cancer Hospital
(Hangzhou, China) were retrospectively investigated. Survival was evaluated using
the Kaplan-Meier method. A total of 248 patients were reviewed, and 158 were
evaluated in the final analysis, with a median age of 57 years and a Karnofsky
performance status score of >=80. The median progression-free survival (PFS) time
was 168 days for first-line chemotherapy, 96 days for second-line chemotherapy,
and the median overall survival (OS) time was 356 days. Further analysis revealed
that patients with the disease controlled [complete response (CR) + partial
response (PR) + stable disease (SD)], no matter whether they received first-or
second-line chemotherapy, may have had an improved OS compared with patients with
disease progression (PD). Patients who were treated with >2 lines of chemotherapy
had an improved OS compared those who ceased treatment following failure of the
second-line chemotherapy. The cycle number of chemotherapy that patients received
was associated with OS. The site of the primary and metastatic tumors was also
associated with OS. Other factors, including gender, age, histological type,
whether a radical operation was received, and chemotherapy regimens, had no
evident association with survival. The toxicities were generally tolerated. Taken
together, the results from the present study have demonstrated that an increased
cycle number of effective chemotherapy may prolong the survival of patients with
advanced gastric cancer. Differences among the chemotherapy regimens had no clear
correlation with survival.
PMID- 28413679
TI - Anorectal functional outcome following laparoscopic low anterior resection for
rectal cancer.
AB - Low anterior resection (LAR) with total mesorectal excision has been considered a
standard treatment for patients with rectal cancer. However, the functional
outcome and life quality of laparoscopic LAR (LLAR) in Chinese patients remain
unclear. A cohort of 51 Chinese patients (22 men and 29 women) who had undergone
LLAR was included in this study. Anorectal manometry combined with the Wexner
scores questionnaire were applied to assess functional outcome preoperatively (1
week) and postoperatively (at 3, 6 and 9 months). The validated Chinese versions
of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ
CR38 questionnaires were also used to assess the patients' quality of life at the
indicated time points. The results demonstrated that the manometric parameters
exhibited a temporary decrease at 3 months postoperatively, but a gradual
increase at 6 and 9 months, while the Wexner scores exhibited an opposite trend.
Furthermore, patients with high anastomoses had significantly higher manometric
parameters, a lower frequency of incontinence and lower Wexner scores compared
with those with low anastomoses at 9 months (all P<0.05). For the entire cohort,
quality of life at 3 months postoperatively was worse compared with the
preoperative level, but returned to normal by 9 months. Patients with high
anastomoses exhibited significantly better role, emotional and social function,
had a better body image and sexual function, fewer problems with defecation and
lower frequency of diarrhea, as well as fewer chemotherapy-related side effects
at 6 months postoperatively when compared with the low anastomosis group (all
P<0.05). In conclusion, LLAR is generally acceptable for Chinese patients with
rectal cancer, particularly for those with middle or high rectal cancer, in terms
of functional outcome and quality of life.
PMID- 28413680
TI - Seven-day capecitabine plus docetaxel and oxaliplatin regimen for the treatment
of advanced gastric cancer: A phase-I clinical trial.
AB - Docetaxel, cisplatin and 5-fluorouracil (DCF regimen) are currently applied as an
effective combination treatment for various human malignancies; however, the
efficacy of this regimen is impaired by severe adverse events associated with it.
Therefore, better-tolerated regimens with comparable efficiency are required for
patients with gastric cancer. To explore such possibilities, a phase-I clinical
trial was performed to evaluate the safety and tolerability of a modified regimen
replacing cisplatin and 5-fluorouracil with oxaliplatin and capecitabine,
respectively (DOX program). The maximum-tolerated dose (MTD) and dose-limited
toxicity (DLT) of capecitabine in this regimen were determined and a dose for
subsequent phase-II clinical trials was identified. A total of 24 patients with
advanced gastric cancer were sequentially enrolled in the present capecitabine
dose-escalation trial. The patients were treated with docetaxel and oxaliplatin
at fixed doses [75 and 100 mg/m2, respectively, intravenously, on day 1 (d1)],
and with capecitabine at increasing doses (1,500, 2,000 and 2,500 mg/m2, per os,
d1-7). The MTD of capecitabine was 2,000 mg/m2 (d1-7), repeated every 21 days for
at least two cycles. The most frequent DLTs for this regimen were leukopenia
(15/24, 62.5%, all at grade-III/IV) and neutropenia (13/24, 54.2%, all at grade
III/IV), nausea (14/24, 58.3%, all at grade-III) and vomiting (13/24, 54.2%, all
at grade-III). The effective rate of the DOX regimen was 75.0% (18/24). Based on
the results, the combination of docetaxel (75 mg/m2, d1), oxaliplatin (100 mg/m2,
d1) and capecitabine (2,000 mg/m2, d1-7) is recommended for a future phase-II
trial. While these doses for the DOX regimen were generally well tolerated, the
efficacy of this modified regimen in patients with advanced gastric cancer
remains to be further evaluated in subsequent phase-II trials.
PMID- 28413681
TI - Phase 2 study of CHOP-R-14 followed by 90Y-ibritumomab tiuxetan in patients with
previously untreated diffuse large B-cell lymphoma.
AB - The aim of this open-label, single-center, phase 2 study was to assess the
efficacy and safety of dose-dense CHOP-R-14 followed by 90Y-ibritumomab
radioimmunotherapy (RIT) in patients with previously untreated diffuse large B
cell lymphoma (DLBCL). A total of 20 patients, the majority presenting with high
risk characteristics, were enrolled to receive dose-dense cyclophosphamide,
doxorubicin, vincristine, prednisone and rituximab every 14 days (CHOP-R-14),
followed by 90Y-ibritumomab tiuxetan consolidation. Sixteen patients completed
RIT consolidation (rituximab 250 mg/m2 on day 1 and day 7, 8, or 9, followed by a
single injection of 90Y-ibritumomab). Complete response (CR) rates of 75 and 95%
were observed after treatment with CHOP-R-14 and RIT, respectively; 4 of the 5
patients who achieved a partial response after CHOP-R-14 converted to CR
following treatment with RIT. With a median follow-up of 89.7 months, the
progression-free and overall survival rates for the cohort were 75 and 85%,
respectively. Hematological adverse events were common following CHOP-R-14 and
RIT, but they were manageable with treatment interruption. Therefore, this
regimen achieved promising survival outcomes in high-risk DLBCL on long term
follow-up, with manageable toxicity.
PMID- 28413682
TI - Multi-focal HIFU reduces cavitation in mild-hyperthermia.
AB - BACKGROUND: Mild-hyperthermia therapy (40-45 degrees C) with high-intensity
focused ultrasound (HIFU) is a technique being considered in a number of
different treatments such as thermally activated drug delivery, immune
stimulation, and as a chemotherapy adjuvant. Mechanical damage and loss of cell
viability associated with HIFU-induced acoustic cavitation may pose a risk during
these treatments or may hinder their success. Here we present a method that
achieves mild heating and reduces cavitation by using a multi-focused HIFU beam.
We quantify cavitation level and temperature rise in multi-focal sonications and
compare it to single-focus sonications at the transducer geometric focus.
METHODS: Continuous wave sonications were performed with the Sonalleve V2
transducer in gel phantoms and pork at 5, 10, 20, 40, 60, 80 acoustic watts for
30 s. Cavitation activity was measured with two ultrasound (US) imaging probes,
both by computing the raw channel variance and using passive acoustic mapping
(PAM). Temperature rise was measured with MR thermometry at 3 T. Cavitation and
heating were compared for single- and multi-focal sonication geometries. Multi
focal sonications used four points equally spaced on a ring of either 4 mm or 8
mm diameter. Single-focus sonications were not steered. RESULTS: Multi-focal
sonication generated distinct foci that were visible in MRI thermal maps in both
phantoms and pork, and visible in PAM images in phantoms only. Cavitation
activity (measured by channel variance) and mean PAM image value were highly
correlated (r > 0.9). In phantoms, cavitation exponentially decreased over the 30
second sonication, consistent with depletion of cavitation nuclei. In pork,
sporadic spikes signaling cavitation were observed with single focusing only. In
both materials, the widest beam reduced average and peak cavitation level by a
factor of two or more at each power tested when compared to a single focus. The
widest beam reduced peak temperature by at least 10 degrees C at powers above 5
W, and created heating that was more spatially diffuse than single focus,
resulting in more voxels in the mild heating (3-8 degrees C) range. CONCLUSIONS:
Multi-focal HIFU can be used to achieve mild temperature elevation and reduce
cavitation activity.
PMID- 28413683
TI - Obtaining accurate glucose measurements from wild animals under field conditions:
comparing a hand held glucometer with a standard laboratory technique in grey
seals.
AB - Glucose is an important metabolic fuel and circulating levels are tightly
regulated in most mammals, but can drop when body fuel reserves become critically
low. Glucose is mobilized rapidly from liver and muscle during stress in response
to increased circulating cortisol. Blood glucose levels can thus be of value in
conservation as an indicator of nutritional status and may be a useful, rapid
assessment marker for acute or chronic stress. However, seals show unusual
glucose regulation: circulating levels are high and insulin sensitivity is
limited. Accurate blood glucose measurement is therefore vital to enable
meaningful health and physiological assessments in captive, wild or rehabilitated
seals and to explore its utility as a marker of conservation relevance in these
animals. Point-of-care devices are simple, portable, relatively cheap and use
less blood compared with traditional sampling approaches, making them useful in
conservation-related monitoring. We investigated the accuracy of a hand-held
glucometer for 'instant' field measurement of blood glucose, compared with blood
drawing followed by laboratory testing, in wild grey seals (Halichoerus grypus),
a species used as an indicator for Good Environmental Status in European waters.
The glucometer showed high precision, but low accuracy, relative to laboratory
measurements, and was least accurate at extreme values. It did not provide a
reliable alternative to plasma analysis. Poor correlation between methods may be
due to suboptimal field conditions, greater and more variable haematocrit, faster
erythrocyte settling rate and/or lipaemia in seals. Glucometers must therefore be
rigorously tested before use in new species and demographic groups. Sampling,
processing and glucose determination methods have major implications for
conclusions regarding glucose regulation, and health assessment in seals
generally, which is important in species of conservation concern and in
development of circulating glucose as a marker of stress or nutritional state for
use in management and monitoring.
PMID- 28413684
TI - Physiological effects of environmentally relevant, multi-day thermal stress on
wild juvenile Atlantic salmon (Salmo salar).
AB - The frequency of extreme thermal events in temperate freshwater systems is
expected to increase alongside global surface temperature. The Miramichi River,
located in eastern Canada, is a prominent Atlantic salmon (Salmo salar) river
where water temperatures can exceed the proposed upper thermal limit for the
species (~27 degrees C). Current legislation closes the river to recreational
angling when water temperatures exceed 20 degrees C for two consecutive nights.
We aimed to examine how natural thermal variation, representative of extreme high
thermal events, affected the thermal tolerance and physiology of wild, juvenile
Atlantic salmon. We acclimated fish to four thermal cycles, characteristic of
real-world thermal conditions while varying daily thermal minima (16 degrees C,
18 degrees C, 20 degrees C or 22 degrees C) and diel thermal fluctuation (e.g.
Delta5 degrees C-Delta9 degrees C). In each cycling condition, we assessed the
role that thermal minima played on the acute thermal tolerance (critical thermal
maximum, (CTMax)), physiological (e.g. heat shock protein 70 (HSP70), ubiquitin)
and energetic (e.g. hepatic glycogen, blood glucose and lactate) status of
juvenile Atlantic salmon throughout repeated thermal cycles. Exposure to 16-21
degrees C significantly increased CTMax (+0.9 degrees C) compared to a stable
acclimation temperature (16 degrees C), as did exposure to diel thermal
fluctuations of 18-27 degrees C, 20-27 degrees C and 22-27 degrees C, yet
repeated exposure provided no further increases in acute thermal tolerance. In
comparison to the reference condition (16-21 degrees C), consecutive days of high
temperature cycling with different thermal minima resulted in significant
increases in HSP70 and ubiquitin, a significant decrease in liver glycogen, and
no significant cumulative effect on either blood glucose or lactate. However,
comparison between thermally taxed treatments suggested the diel thermal minima
had little influence on the physiological or energetic response of juvenile
salmon, despite the variable thermal cycling condition. Our results suggest that
relatively cooler night temperatures in the summer months may play a limited role
in mitigating physiological stress throughout warm diel cycle events.
PMID- 28413685
TI - Empyema associated with Campylobacter curvus infection.
AB - We report the first case of thoracic empyema associated with Campylobacter curvus
infection. A 65-year-old woman with a history of bronchiectasis presented with
acute cough and phlegm. The patient reported dyspnoea and left chest pain
accompanied by left pleural effusion, despite treatment with sitafloxacin. Curved
Gram-negative rods, eventually identified as C. curvus using 16S ribosomal RNA-
and atpA-specific polymerase chain reaction (PCR) and sequencing, were cultured
in anaerobic condition of pleural effusion together with Peptostreptococci. The
patient recovered after thoracic drainage and treatment with ampicillin/sulbactam
and clindamycin. C. curvus, an anaerobe present in human oral cavity, can be
associated with extra-oral infections such as empyema.
PMID- 28413686
TI - Cytokine profiles of amyopathic dermatomyositis with interstitial lung diseases
treated with mycophenolate.
AB - A 59-year-old Japanese man diagnosed with interstitial lung disease associated
with amyopathic dermatomyositis with anti-melanoma differentiation-associated
gene 5 (MDA-5) antibodies was treated with intravenous methyl prednisolone (PSL)
1000 mg, oral PSL 1 mg/kg, and oral cyclosporin 200 mg daily. His respiratory
condition worsened after treatment with two times of intravenous cyclophosphamide
and another steroid pulse therapy as well as PSL and cyclosporin. Addition of
mycophenolate mofetil (MMF), 1.5 g daily improved PaO2/FiO2 (PF) ratio of the
patient from 294 to 360 at 4 weeks and 416 at 15 weeks after addition of MMF. We
measured cytokine concentration in preserved serum taken at 11 and 7 weeks before
addition of MMF and at 4, 11, and 15 weeks after MMF administration. Of the 28
cytokines evaluated, the concentrations of fibroblast growth factors-2 (FGF-2),
chemokine (C-X3-C motif) ligand 1 (CX3CL1), interleukin (IL)-1ra, IL-17A,
inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1)
decreased after addition of MMF. These results suggest that MMF may be beneficial
to patients with interstitial lung disease by modification of the cytokine/growth
factor protein expression.
PMID- 28413687
TI - What we have changed our minds about: Part 1. Borderline personality disorder as
a limitation of resilience.
AB - This paper sets out a recent transition in our thinking in relation to
psychopathology associated with personality disorder, in an approach that
integrates our thinking about attachment, mentalizing (understanding ourselves
and others in terms of intentional mental states) and epistemic trust (openness
to the reception of social communication that is personally relevant and of
generalizable significance) with recent findings on the structure of both adult
and child psychopathology and resilience. In this paper - the first of two parts
we review evidence suggesting that a general psychopathology or p factor
underlies vulnerability for psychopathology. We link this p factor to a lack of
resilience using Kalisch and colleagues' positive appraisal style theory of
resilience (PASTOR). We argue that vulnerability for (severe) psychopathology
results from impairments in three central mechanisms underlying resilience -
positive situation classification, retrospective reappraisal of threat, and
inhibition of retraumatizing triggers - which in turn result from a lack of
flexibility in terms of social communicative processes. We suggest that, from
this perspective, personality disorders, and borderline personality disorder
(BPD) in particular, can be considered to be the prototype of disorders
characterized by a lack of resilience. Part 2 proposes an evolutionary
developmental psychopathology account linking this inflexibility in social
communication to problems with the development of epistemic trust - that is, an
evolutionary pre-wired social communication system that normally facilitates
resilience through salutogenesis, that is, the capacity to learn and derive
benefit from the (social) environment.
PMID- 28413688
TI - Presentation and care of a family with Huntington disease in a resource-limited
community.
AB - BACKGROUND: In high-income countries patients with Huntington disease (HD)
typically present to healthcare providers after developing involuntary movements,
or for pre-symptomatic genetic testing if at familial risk. A positive family
history is a major guide when considering the decision to perform genetic testing
for HD, both in affected and unaffected patients. Management of HD is focused
upon control of symptoms, whether motor, cognitive, or psychiatric. There is no
clear evidence to date of any disease-modifying agents. Referral of families and
caregivers for psychological and social support, whether to HD-focused centers,
or through virtual communities, is viewed as an important consequence of
diagnosis. The experience of healthcare for such progressive neurodegenerative
diseases in low- and middle-income nations is in stark contrast with the standard
of care in high-income countries. METHODS: An extended family with many members
affected with an autosomal dominantly inherited movement disorder came to medical
attention when one family member presented following a fall. Apart from one
family member who was taking a benzodiazepine for involuntary movements, no other
affected family members had sought medical attention. Members of this family live
on several resource-limited Caribbean islands. Care of the chronically ill is
often the responsibility of the family, and access to specialty care is difficult
to obtain, or is unavailable. Computed tomography scan of one patient's brain
revealed severe caudate atrophy and moderate generalized cortical atrophy.
Genetic diagnosis of HD was obtained. RESULTS: Through family recollection and by
direct observation we identified four generations of individuals affected with
HD. Outreach programs and collaborations helped to provide medical imaging and
genetic diagnosis. Additionally these efforts helped with patient and family
support, education, and genetic counseling to many members of this family.
CONCLUSIONS: Affected members of this family have limited healthcare access, and
rely heavily on family support for care. Genetic and clinical diagnosis of these
patients was impeded by lack of resources and lack of access to specialty care.
Importantly, obtaining a definitive diagnosis has had a positive impact for this
family by facilitating genetic counseling, education, community outreach, and
dispelling myths regarding this hereditary disease and its progression.
PMID- 28413689
TI - L1000CDS2: LINCS L1000 characteristic direction signatures search engine.
AB - The library of integrated network-based cellular signatures (LINCS) L1000 data
set currently comprises of over a million gene expression profiles of chemically
perturbed human cell lines. Through unique several intrinsic and extrinsic
benchmarking schemes, we demonstrate that processing the L1000 data with the
characteristic direction (CD) method significantly improves signal to noise
compared with the MODZ method currently used to compute L1000 signatures. The CD
processed L1000 signatures are served through a state-of-the-art web-based search
engine application called L1000CDS2. The L1000CDS2 search engine provides
prioritization of thousands of small-molecule signatures, and their pairwise
combinations, predicted to either mimic or reverse an input gene expression
signature using two methods. The L1000CDS2 search engine also predicts drug
targets for all the small molecules profiled by the L1000 assay that we
processed. Targets are predicted by computing the cosine similarity between the
L1000 small-molecule signatures and a large collection of signatures extracted
from the gene expression omnibus (GEO) for single-gene perturbations in mammalian
cells. We applied L1000CDS2 to prioritize small molecules that are predicted to
reverse expression in 670 disease signatures also extracted from GEO, and
prioritized small molecules that can mimic expression of 22 endogenous ligand
signatures profiled by the L1000 assay. As a case study, to further demonstrate
the utility of L1000CDS2, we collected expression signatures from human cells
infected with Ebola virus at 30, 60 and 120 min. Querying these signatures with
L1000CDS2 we identified kenpaullone, a GSK3B/CDK2 inhibitor that we show, in
subsequent experiments, has a dose-dependent efficacy in inhibiting Ebola
infection in vitro without causing cellular toxicity in human cell lines. In
summary, the L1000CDS2 tool can be applied in many biological and biomedical
settings, while improving the extraction of knowledge from the LINCS L1000
resource.
PMID- 28413690
TI - A dynamic model for GPS based attitude determination and testing using a serial
robotic manipulator.
AB - A computational algorithm is developed for estimating accurately the attitude of
a robotic arm which moves along a predetermined path. This algorithm requires
preliminary input data obtained in the static mode to yield phase observables for
the precise, 3-axis attitude determination of a swinging manipulator in the
dynamic mode. Measurements are recorded simultaneously by three GPS L1 receivers
and then processed in several steps to accomplish this task. First, artkconv
batch executable converts GPS receiver readings into RINEX format to generate GPS
observables and ephemeris for multiple satellites. Then baseline vectors
determination is carried out by baseline constrained Least-Squares Ambiguity
Decorrelation (LAMBDA) method that uses double difference carrier phase estimates
as input to calculate integer solution for each baseline. Finally, attitude
determination is made by employing alternatively Least-squares attitude
determination (LSAD) in the static mode and extended Kalman filter in the dynamic
mode. The algorithm presented in this paper is applied to recorded data on
Mitsubishi RV-M1 robotic arm in order to produce attitude estimates. These
results are confirmed by another set of Euler angles independently evaluated from
robotic arm postures obtained along the predefined trajectory.
PMID- 28413691
TI - Proton Transfer in the Catalytic Cycle of [NiFe] Hydrogenases: Insight from
Vibrational Spectroscopy.
AB - Catalysis of H2 production and oxidation reactions is critical in renewable
energy systems based around H2 as a clean fuel, but the present reliance on
platinum-based catalysts is not sustainable. In nature, H2 is oxidized at minimal
overpotential and high turnover frequencies at [NiFe] catalytic sites in
hydrogenase enzymes. Although an outline mechanism has been established for the
[NiFe] hydrogenases involving heterolytic cleavage of H2 followed by a first and
then second transfer of a proton and electron away from the active site, details
remain vague concerning how the proton transfers are facilitated by the protein
environment close to the active site. Furthermore, although [NiFe] hydrogenases
from different organisms or cellular environments share a common active site,
they exhibit a broad range of catalytic characteristics indicating the importance
of subtle changes in the surrounding protein in controlling their behavior. Here
we review recent time-resolved infrared (IR) spectroscopic studies and IR
spectroelectrochemical studies carried out in situ during electrocatalytic
turnover. Additionally, we re-evaluate the significant body of IR spectroscopic
data on hydrogenase active site states determined through more conventional
solution studies, in order to highlight mechanistic steps that seem to apply
generally across the [NiFe] hydrogenases, as well as steps which so far seem
limited to specific groups of these enzymes. This analysis is intended to help
focus attention on the key open questions where further work is needed to assess
important aspects of proton and electron transfer in the mechanism of [NiFe]
hydrogenases.
PMID- 28413693
TI - Stable Fe/ZSM-5 Nanosheet Zeolite Catalysts for the Oxidation of Benzene to
Phenol.
AB - Fe/ZSM-5 nanosheet zeolites of varying thickness were synthesized with di- and
tetraquaternary ammonium structure directing agents and extensively characterized
for their textural, structural, and catalytic properties. Introduction of Fe3+
ions in the framework of nanosheet zeolites was slightly less effective than in
bulk ZSM-5 zeolite. Steaming was necessary to activate all catalysts for N2O
decomposition and benzene oxidation. The higher the Fe content, the higher the
degree of Fe aggregation was after catalyst activation. The degree of Fe
aggregation was lower when the crystal domain size of the zeolite or the Fe
content was decreased. These two parameters had a substantial influence on the
catalytic performance. Decreasing the number of Fe sites along the b-direction
strongly suppressed secondary reactions of phenol and, accordingly, catalyst
deactivation. This together with the absence of diffusional limitations in
nanosheet zeolites explains the much higher phenol productivity obtainable with
nanostructured Fe/ZSM-5. Steamed Fe/ZSM-5 zeolite nanosheet synthesized using C22
6-3.Br2 (domain size in b-direction ~3 nm) and containing 0.24 wt % Fe exhibited
the highest catalytic performance. During the first 24 h on stream, this catalyst
produced 185 mmolphenol g-1. Calcination to remove the coke deposits completely
restored the initial activity.
PMID- 28413692
TI - Photoredox-Mediated Routes to Radicals: The Value of Catalytic Radical Generation
in Synthetic Methods Development.
AB - Photoredox catalysis has experienced a revitalized interest from the synthesis
community during the past decade. For example, photoredox/Ni dual catalysis
protocols have been developed to overcome several inherent limitations of
palladium-catalyzed cross-couplings by invoking a single-electron transmetalation
pathway. This Perspective highlights advances made by our laboratory since the
inception of the photoredox/Ni cross-coupling of benzyltrifluoroborates with aryl
bromides. In addition to broadening the scope of trifluoroborate coupling
partners, research using readily oxidized hypervalent silicates as radical
precursors that demonstrate functional group compatibility is highlighted. The
pursuit of electrophilic coupling partners beyond (hetero)aryl bromides has also
led to the incorporation of several new classes of C(sp2)-hybridized substrates
into light-mediated cross-coupling. Advances to expand the radical toolbox by
utilizing feedstock chemicals (e.g., aldehydes) to access radicals that were
previously inaccessible from trifluoroborates and silicates are also emphasized.
Additionally, several organic photocatalysts have been investigated as
replacements for their expensive iridium- and ruthenium-based counterparts.
Lastly, the net C-H functionalization of the radical partner in an effort to
improve atom economy is presented. An underlying theme in all of these studies is
the value of generating radicals in a catalytic manner, rather than
stoichiometrically.
PMID- 28413694
TI - First Neonatal Demise with Travel-Associated Zika Virus Infection in the United
States of America.
AB - Zika virus is increasingly recognized as a fetal pathogen worldwide. We describe
the first case of neonatal demise with travel-associated Zika virus infection in
the United States of America, including a novel prenatal ultrasound finding. A
young Latina presented to our health care system in Southeast Texas for prenatal
care at 23 weeks of gestation. Fetal Dandy-Walker malformation, asymmetric
cerebral ventriculomegaly, single umbilical artery, hypoechoic fetal knee, dorsal
foot edema, and mild polyhydramnios were noted upon initial screening prenatal
sonography at 26 weeks. A growth-restricted, microcephalic, and arthrogrypotic
infant was delivered alive at 36 weeks but died within an hour despite
resuscitation. The neonatal karyotype was normal. Flavivirus IgM antibodies were
identified in the serum of the puerpera, once she disclosed that she had traveled
from El Salvador to Texas in the early second trimester. Zika virus was
identified in the umbilical cord and neonatal brain. Fetal arthritis may precede
congenital arthrogryposis in cases of Zika virus infection and may be detectable
by prenatal sonography. Physician and health care system vigilance is required to
optimally address the significant and enduring Zika virus global health threat.
PMID- 28413695
TI - One-step Quantitative RT-PCR Assays for Detecting, Genotyping and Differentiating
Wild-Type Group a Rotaviruses and Vaccine (Rotarix(r) and RotaTeq(r)) Strains in
Stool Samples.
PMID- 28413696
TI - Prevalence of potential sports-associated risk factors in Swiss amyotrophic
lateral sclerosis patients.
AB - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) has been reported to occur with
increased incidence amongst physically active people. The role of extrinsic risk
factors as physical activity, head trauma and drug/pesticide-exposure in the
pathophysiology of ALS and especially in the context of practising sports remains
controversial. MATERIALS AND METHODS: We retrospectively studied exposure to
extrinsic factors in 92 ALS patients in the presymptomatic stage. Metabolic
equivalents (METs) were calculated and the association of physical activity, drug
intake, head trauma and participation in specific sports (football [soccer], ice
hockey) with age at symptom-onset was evaluated. RESULTS: Ninety-five percent of
patients considered themselves physically active before symptom-onset. Total MET
values varied broadly and there was no correlation between vigorous physical
activity and age at symptom-onset. Mild traumatic brain injury (prevalence =
16.7%) was the most frequent diagnosis after head/neck injury. A history of >=1
head/neck injuries was associated with a younger age at symptom-onset (61.8 +/-
11.0 vs. 54.1 +/- 13.0, p = .013). In former football and ice hockey players the
rate of vigorous physical activities was increased (p < .05), whereas total MET
values, frequency of head injuries and analgesic intake were not different
compared to other ALS patients. CONCLUSIONS: History of head injuries was the
only extrinsic risk factor associated with accelerated neurodegeneration in ALS.
There was no evidence for extrinsic factors predisposing former football and ice
hockey players to ALS. Our data therefore support the hypothesis that not
increased physical activity per se, but other unknown environmental factors
and/or genetic profile or lifestyle-promoting physical fitness increases ALS
susceptibility.
PMID- 28413697
TI - Acute ethanol exposure during late mouse neurodevelopment results in long-term
deficits in memory retrieval, but not in social responsiveness.
AB - OBJECTIVE: Prenatal alcohol exposure can result in neurological changes in
affected individuals and may result in the emergence of a broad spectrum of
neurobehavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The
effects of ethanol exposure during development are both time and dose dependent.
Although many animal models of FASD use more chronic ethanol exposure, acute
developmental alcohol exposure may also cause long-lasting neuronal changes. Our
research employed behavioral measures to assess the effects of a single early
postnatal ethanol intoxication event in mice. MATERIALS AND METHODS: Mice were
dosed at postnatal day 6 (a 2.5 g/kg dose of ethanol or a saline control
administered twice, 2 hr apart) as a model of third trimester binge drinking in
humans. This exposure was followed by behavioral assessment in male mice at 1
month (1M) and at 4 months of age (4M), using the Barnes maze (for
learning/memory retrieval), exploratory behavior, and a social responsiveness
task. RESULTS: Ethanol-exposed mice appeared to be less motivated to complete the
Barnes maze at 1M, but were able to successfully learn the maze. However,
deficits in long-term spatial memory retrieval were observed in ethanol-exposed
mice when the Barnes maze recall was measured at 4M. No significant differences
were found in open field behavior or social responsiveness at 1M or 4M of age.
CONCLUSIONS: Acute ethanol exposure at P6 in mice leads to mild but long-lasting
deficits in long-term spatial memory. Results suggest that even brief acute
exposure to high ethanol levels during the third trimester equivalent of human
pregnancy may have a permanent negative impact on the neurological functioning of
the offspring.
PMID- 28413698
TI - Simultaneous bilateral cochlear implants: Developmental advances do not yet
achieve normal cortical processing.
AB - BACKGROUND: Simultaneous bilateral cochlear implantation promotes symmetric
development of bilateral auditory pathways but binaural hearing remains abnormal.
To evaluate whether bilateral cortical processing remains impaired in such
children, cortical activity to unilateral and bilateral stimuli was assessed in a
unique cohort of 16 children who received bilateral cochlear implants (CIs)
simultaneously at 1.97 +/- 0.86 years of age and had ~4 years of CI experience,
providing the first opportunity to assess electrically driven cortical
development in the absence of reorganized asymmetries from sequential
implantation. METHODS: Cortical activity to unilateral and bilateral stimuli was
measured using multichannel electro-encephalography. Cortical processing in
children with bilateral CIs was compared with click-elicited activity in 13
normal hearing children matched for time-in-sound. Source activity was localized
using the Time Restricted, Artefact and Coherence source Suppression (TRACS)
beamformer method. RESULTS: Consistent with dominant crossed auditory pathways,
normal P1 activity (~100 ms) was weaker to ipsilateral stimuli relative to
contralateral and bilateral stimuli and both auditory cortices preferentially
responded to the contralateral ear. Right hemisphere dominance was evident
overall. Children with bilateral CIs maintained the expected right dominance but
differences from normal included: (i) minimal changes between ipsilateral,
contralateral and bilateral stimuli, (ii) weaker than normal contralateral
stimulus preference, (iii) symmetric activity to bilateral stimuli, and (iv)
increased occipital lobe recruitment during bilateral relative to unilateral
stimulation. Between-group contrasts demonstrated lower than normal activity in
the inferior parieto-occipital lobe (suggesting deficits in sensory integration)
and greater than normal left frontal lobe activity (suggesting increased
attention), even during passive listening. CONCLUSIONS: Together, findings
suggest that early simultaneous bilateral cochlear implantation promotes normal
like auditory symmetry but that abnormalities in cortical processing consequent
to deafness and/or electrical stimulation through two independent speech
processors persist.
PMID- 28413699
TI - White matter connections of the inferior parietal lobule: A study of surgical
anatomy.
AB - INTRODUCTION: Interest in the function of the inferior parietal lobule (IPL) has
resulted in increased understanding of its involvement in visuospatial and
cognitive functioning, and its role in semantic networks. A basic understanding
of the nuanced white-matter anatomy in this region may be useful in improving
outcomes when operating in this region of the brain. We sought to derive the
surgical relationship between the IPL and underlying major white-matter bundles
by characterizing macroscopic connectivity. METHODS: Data of 10 healthy adult
controls from the Human Connectome Project were used for tractography analysis.
All IPL connections were mapped in both hemispheres, and distances were recorded
between cortical landmarks and major tracts. Ten postmortem dissections were then
performed using a modified Klingler technique to serve as ground truth. RESULTS:
We identified three major types of connections of the IPL. (1) Short association
fibers connect the supramarginal and angular gyri, and connect both of these gyri
to the superior parietal lobule. (2) Fiber bundles from the IPL connect to the
frontal lobe by joining the superior longitudinal fasciculus near the termination
of the Sylvian fissure. (3) Fiber bundles from the IPL connect to the temporal
lobe by joining the middle longitudinal fasciculus just inferior to the margin of
the superior temporal sulcus. CONCLUSIONS: We present a summary of the relevant
anatomy of the IPL as part of a larger effort to understand the anatomic
connections of related networks. This study highlights the principle white-matter
pathways and highlights key underlying connections.
PMID- 28413700
TI - Endovascular stroke treatment in a small-volume stroke center.
AB - INTRODUCTION: Our purpose was to evaluate the safety and efficacy of endovascular
treatment (EVT) of stroke caused by large vessel occlusions (LVO) performed by
general interventional radiologists in cooperation with stroke neurologists and
neuroradiologists at a center with a limited annual number of procedures. We
aimed to compare our results with those previously reported from larger stroke
centers. PATIENTS AND METHODS: A total of 108 patients with acute stroke due to
LVO treated with EVT were included. Outcome was measured using the modified
Rankin scale (mRS) at 90 days. Efficacy was classified according to the modified
thrombolysis in cerebral infarction (mTICI) scoring system. Safety was evaluated
according to the incidence of procedural complications and symptomatic
intracranial hemorrhage (sICH). RESULTS: Mean age of the patients was 67.5 years.
The median National Institutes of Health Stroke Scale (NIHSS) on hospital
admission was 17. Successful revascularization was achieved in 76%. 39.4%
experienced a good clinical outcome (mRS<3). Intraprocedural complications were
seen in 7.4%. 7.4% suffered a sICH. 21.3% died within 3 months after EVT.
DISCUSSION: The use of general interventional radiologists in EVT of LVO may be a
possible approach for improving EVT coverage where availability of specialized
neurointerventionalists is challenging. EVT for LVO stroke performed by general
interventional radiologists in close cooperation with diagnostic
neuroradiologists and stroke neurologists can be safe and efficacious despite the
low number of annual procedures.
PMID- 28413701
TI - Elevated C-X-C motif ligand 13 and B-cell-activating factor levels in
neuromyelitis optica during remission.
AB - BACKGROUND: Discovery of specific antibodies against astrocytic water channel
aquaporin-4 (AQP4), which is produced by plasma cells, in the serum of
neuromyelitis optica (NMO) confirmed the pathogenic role of B cells in NMO. C-X-C
motif ligand 13 (CXCL13) and B-cell-activating factor (BAFF) are two crucial
factors for antibody production. Relevant studies have focused on the acute phase
of NMO. However, CXCL13 and BAFF levels during remission, remain to be
elucidated. OBJECTIVE: To evaluate serum levels of CXCL13 and BAFF in NMO and
multiple sclerosis (MS) patients during remission and explore their correlation
with immunosuppressive agents and clinical features in NMO. METHODS: Serum CXCL13
and BAFF were measured by enzyme-linked immunosorbent assay (ELISA) in NMO
patients, MS patients, and controls. RESULTS: Serum CXCL13 levels of NMO patients
(n = 24) were significantly higher than those of controls (n = 22) (p = .001),
but CXCL13 levels of MS patients (n = 20) and controls (n = 22) did not differ
significantly (p = .279). Although the three groups showed no differences in
serum BAFF levels, serum BAFF levels of NMO patients without immunosuppressive
treatment (n = 8) were significantly elevated compared with those of NMO patients
with immunosuppressive therapy (n = 16) (p = .003) and controls (n = 22) (p =
.024). In NMO patients, CXCL13 levels were correlated with onset age (p = .026)
and duration to the last relapse (p = .003). CONCLUSION: During remission, serum
CXCL13 and BAFF levels have not decreased to normal in NMO patients, and B-cell
related autoimmune response persists. Immunosuppressive therapy decreased serum
BAFF levels, but did not affect CXCL13 expression.
PMID- 28413702
TI - Targeted sequencing identifies genetic polymorphisms of flavin-containing
monooxygenase genes contributing to susceptibility of nicotine dependence in
European American and African American.
AB - BACKGROUND: Smoking is a leading cause of preventable death. Early studies based
on samples of twins have linked the lifetime smoking practices to genetic
predisposition. The flavin-containing monooxygenase (FMO) protein family consists
of a group of enzymes that metabolize drugs and xenobiotics. Both FMO1 and FMO3
were potentially susceptible genes for nicotine metabolism process. METHODS: In
this study, we investigated the potential of FMO genes to confer risk of nicotine
dependence via deep targeted sequencing in 2,820 study subjects comprising 1,583
nicotine dependents and 1,237 controls from European American and African
American. Specifically, we focused on the two genomic segments including
FMO1,FMO3, and pseudo gene FMO6P, and aimed to investigate the potential
association between FMO genes and nicotine dependence. Both common and low
frequency/rare variants were analyzed using different algorithms. The potential
functional significance of SNPs with association signal was investigated with
relevant bioinformatics tools. RESULTS: We identified different clusters of
significant common variants in European (with most significant SNP rs6674596, p =
.0004, OR = 0.67, MAF_EA = 0.14, FMO1) and African Americans (with the most
significant SNP rs6608453, p = .001, OR = 0.64, MAF_AA = 0.1, FMO6P). No
significant signals were identified through haplotype-based analyses. Gene
network investigation indicated that both FMO1 and FMO3 have a strong relation
with a variety of genes belonging to CYP gene families (with combined score
greater than 0.9). Most of the significant variants identified were SNPs located
within intron regions or with unknown functional significance, indicating a need
for future work to understand the underlying functional significance of these
signals. CONCLUSIONS: Our findings indicated significant association between FMO
genes and nicotine dependence. Replications of our findings in other ethnic
groups were needed in the future. Most of the significant variants identified
were SNPs located within intronic regions or with unknown functional
significance, indicating a need for future work to understand the underlying
functional significance of these signals.
PMID- 28413703
TI - Lifelong neurogenesis in the cerebral ganglion of the Chinese mud snail,
Cipangopaludina chinensis.
AB - INTRODUCTION: A small group of Gastropods possessing giant neurons have long been
used to study a wide variety of fundamental neurophysiological phenomena.
However, the majority of gastropods do not have large neurons but instead have
large numbers of small neurons and remain largely unstudied. We explored neuron
size and rate of increase in neuron numbers in the Chinese mud snail,
Cipangopaludina chinensis. METHODS: Using histological sections and whole mounts
of the cerebral ganglia, we collected cross-sectional data on neuron number and
size across the lifespan of this animal. Neurogenesis was verified using Click-it
EdU staining. RESULTS: We found that total neuron number in the cerebral ganglia
increases throughout the lifespan of this species at a constant rate. New neurons
arise primarily near the nerve roots. Females live longer (up to 7 years) than
males (up to 5 years) and thus achieve larger numbers of neurons in the cerebral
ganglion. Neuron size is consistently small (<10 MUm) in the cerebral ganglia at
all ages, however, cells in the posterior section of the cerebral ganglia are
modestly but significantly larger than cells at the anterior. CONCLUSIONS: These
features suggest that C. chinensis and similar species of Caenogastropoda are
good candidates for studying gastropod neurogenesis, senescence, and sex
differences in the nervous system.
PMID- 28413704
TI - Diversity in mental fatigue and social profile of patients with myasthenia gravis
in two different Northern European countries.
AB - : Self-estimated health can be used for comparison of different diseases between
countries. It is important to elaborate on whether disparities in self-estimated
health are due to disease-specific parameters or socioeconomic differences. In
this study, we aimed at evaluating clinical and social similarities and
differences in myasthenia gravis (MG) patients between comparable regions in two
Baltic Sea countries, Estonia and Sweden. METHODS: This cross-sectional study
included southern counties in Sweden and Estonia of comparable size. All patients
with a confirmed MG diagnosis were asked to answer two questionnaires including
demographic and disease-specific data, lifestyle issues, and mental fatigue
(Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through
the Quantitative Myasthenia Gravis Score (QMG). RESULTS: Thirty-six of 92
identified patients in Estonia and 40 of 70 identified MG patients in Sweden
chose to participate in the study. The demographic characteristics and symptoms
reported by the patients were similar. QMG score did not differ; however, the
Estonian patients scored their current subjective disease severity significantly
higher (5.6 +/- 2.8) compared to the Swedish patients (3.4 +/- 2.3, p = .0005).
Estonian patients also had significantly higher FSS scores (5.0 +/- 1.7) than
Swedish patients (3.5 +/- 1.6; p = .001). Swedish patients were more active and
performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden,
p = .004). CONCLUSIONS: Although, the patients had comparable clinical fatigue,
Estonian patients evaluated their health state as being more severe and reported
more mental fatigue than Swedish patients. These data indicate large regional
differences in disease perception of MG, which is important to consider in
international studies.
PMID- 28413705
TI - Acute stroke alert activation, emergency service use, and reperfusion therapy in
Sweden.
AB - OBJECTIVES: Ambulance services and stroke alerts reduce the time from stroke
onset to acute stroke diagnosis. We describe the use of stroke alerts and
ambulance services in different hospitals and patient groups and their
relationship with reperfusion therapy. METHODS: This nationwide study included
49,907 patients admitted with acute stroke who were registered in The Swedish
Stroke Register (Riksstroke) in 2011-2012. RESULTS: The proportions of patients
admitted as stroke alerts out of all acute stroke admissions varied from 12.2% to
45.7% in university hospitals (n = 9), 0.5% to 38.7% in specialized nonuniversity
hospitals (n = 22), and 4.2% to 40.3% in community hospitals (n = 41). Younger
age, atrial fibrillation (AF), living in an institution, reduced consciousness
upon admission, and hemorrhagic stroke were factors associated with a higher
probability of stroke alerts. Living alone, primary school education, non
European origin, previous stroke, diabetes, smoking, and dependency in activities
of daily living (ADL) were associated with a lower probability of stroke alert.
The proportion of patients arriving at the hospital by ambulance varied from
60.3% to 94.5%. Older age, living alone, primary school education, being born in
a European country, previous stroke, AF, dependency in ADL, living in an
institution, reduced consciousness upon admission, and hemorrhagic stroke were
associated with ambulance services. Hospital stroke alert frequencies correlated
strongly with reperfusion rates (r = .75). CONCLUSION: Acute stroke alerts have a
significant potential to improve stroke reperfusion rates. Prehospital stroke
management varies conspicuously between hospitals and patient groups, and the
elderly and patients living alone have a markedly reduced likelihood of stroke
alerts.
PMID- 28413706
TI - Basic taste processing recruits bilateral anteroventral and middle dorsal
insulae: An activation likelihood estimation meta-analysis of fMRI studies.
AB - BACKGROUND AND PURPOSE: Numerous task-based functional magnetic resonance imaging
(fMRI) studies have reported the locations of basic taste representations in the
human brain, but they usually employed a limited number of subjects (<20) with
different methodologies and stimuli. Moreover, the reported brain regions were
sometimes inconsistent. Thus, we aimed at performing a meta-analysis of the
published data to identify locations consistently activated across studies, and
performed a connectivity analysis to reveal how these taste processing regions
connect with other brain regions. MATERIALS AND METHODS: A meta-analysis was
performed based on 34 experiments, with 238 total participants in 16 studies, to
establish the activation likelihood estimation (ALE) of taste-mediated regional
activation. Meta-analytic connectivity modeling (MACM) and data stored in
BrainMap database were employed to reveal the functional connectivity of the
regions identified by ALE with other brain regions, across all types of
experiments that caused activation among healthy subjects. RESULTS: ALE
identified nine activated clusters in bilateral anteroventral and middle dorsal
insulae, bilateral thalamus and caudate, bilateral pre-/postcentral gyrus, and
right hippocampus. The concurrence between studies was moderate, with at best 38%
of experiments contributed to the significant clusters activated by taste
stimulation. Sweet taste was the predominant contributing taste. MACM revealed
that at least 50% of the nine clusters coactivated with the middle cingulate
cortex, medial frontal gyrus, inferior parietal lobule, and putamen. CONCLUSION:
Results suggested that fMRI studies have reported reproducible patterns of
activations across studies. The basic taste stimulations resulted in activations
in a mostly bilateral network. Moreover, they were connected with cognitive and
emotional relevant brain regions.
PMID- 28413707
TI - Disrupting dorsolateral prefrontal cortex by rTMS reduces the P300 based marker
of deception.
AB - OBJECTIVE: Quite many studies have revealed certain brain-process signatures
indicative of subject's deceptive behavior. These signatures are neural
correlates of deception. However, much less is known about whether these
signatures can be modified by noninvasive brain stimulation techniques
representing methods of causal intervention of brain processes and the
corresponding behavior. Our purpose was to explore whether such methods have an
effect on these signatures. METHODS: It is well known that
electroencephalographic event-related potential component, P300, is sensitive to
perception of critical items in a concealed information test, one of the central
methods in deception studies. We examined whether the relative level of
expression of P300 as a neural marker of deception can be manipulated by means of
noninvasive neuromodulation. We used EEG/ERP recording combined with (i)
neuronavigated repetitive transcranial magnetic stimulation (rTMS) and (ii)
concealed information detection test. An opportunistically recruited volunteer
group of normal adults formed our experimental group. RESULTS: We show that
offline rTMS to dorsolateral prefrontal cortex attenuated relative P300 amplitude
in response to the critical items compared to the neutral items. CONCLUSION:
Noninvasive prefrontal cortex excitability disruption by rTMS can be used to
manipulate the sensitivity of ERP signatures of deception to critical items in a
concealment-based variant of lie detection test.
PMID- 28413708
TI - Neural evidence for phonologically based language production deficits in older
adults: An fMRI investigation of age-related differences in picture-word
interference.
AB - INTRODUCTION: Older adults often show declines in phonological aspects of
language production, particularly for low-frequency words, but maintain strong
semantic systems. However, there are different theories about the mechanism that
may underlie such age-related differences in language (e.g., age-related declines
in transmission of activation or inhibition). METHODS: This study used fMRI to
investigate whether age-related differences in language production are associated
with transmission deficits or inhibition deficits. We used the picture-word
interference paradigm to examine age-related differences in picture naming as a
function of both target frequency and the relationship between the target picture
and distractor word. RESULTS: We found that the presence of a categorically
related distractor led to greater semantic elaboration by older adults compared
to younger adults, as evidenced by older adults' increased recruitment of regions
including the left middle frontal gyrus and bilateral precuneus. When presented
with a phonologically related distractor, patterns of neural activation are
consistent with previously observed age deficits in phonological processing,
including age-related reductions in the recruitment of regions such as the left
middle temporal gyrus and right supramarginal gyrus. Lastly, older, but not
younger, adults show increased brain activation of the pre- and postcentral gyri
as a function of decreasing target frequency when target pictures are paired with
a phonological distractor, suggesting that cuing the phonology of the target
disproportionately aids production of low-frequency items. CONCLUSIONS: Overall,
this pattern of results is generally consistent with the transmission deficit
hypothesis, illustrating that links within the phonological system, but not the
semantic system, are weakened with age.
PMID- 28413710
TI - Combination of standard axial and thin-section coronal diffusion-weighted imaging
facilitates the diagnosis of brainstem infarction.
AB - BACKGROUND AND PURPOSE: Although diffusion-weighted imaging (DWI) is a very
sensitive technique for the detection of small ischemic lesions in the human
brain, in particular in the brainstem it may fail to demonstrate acute ischemic
infarction. In this study, we sought to evaluate the value of additional thin
section coronal DWI for the detection of brainstem infarction. METHODS: In 155
consecutive patients (median age 69 [interquartile range, IQR 57-78] years, 95
[61.3%] males) with isolated brainstem infarction, MRI findings were analyzed,
with emphasis on ischemic lesions on standard axial (5 mm) and thin-section
coronal (3 mm) DWI. RESULTS: On DWI, we identified ischemic lesions in the
mesencephalon in 12 (7.7%), pons in 115 (74.2%), and medulla oblongata in 31
(20%) patients. In 3 (1.9%) cases-all of these with medulla oblongata infarction
the ischemic lesion was detected only on thin-section coronal DWI. Overall, in 35
(22.6%) patients the ischemic lesion was more easily identified on thin-section
coronal DWI in comparison to standard axial DWI. In these, the ischemic lesions
were significantly smaller (0.06 [IQR 0.05-0.11] cm3 vs. 0.25 [IQR 0.13-0.47]
cm3; p < .001) in comparison to those patients whose ischemic lesion was more
easily (6 [3.9%]) or at least similarly well identified (114 [73.5%]) on standard
axial DWI. CONCLUSIONS: Since thin-section coronal DWI may facilitate the
diagnosis of brainstem infarction, we suggest its inclusion in standard stroke
MRI protocols.
PMID- 28413709
TI - Awareness, apathy, and depression in Alzheimer's disease and mild cognitive
impairment.
AB - INTRODUCTION: Results from studies on awareness disorders in Alzheimer's disease
(AD) are controversial because the methodologies, the "objects" of awareness, and
the patients' pathologic stage all vary. Our study aimed to compare scores and
correlates of awareness according to the stage of the disease and the assessment
method. METHODS: We compared 20 mild AD patients to 20 mild cognitive impairment
(MCI) patients, using the Patient Competency Rating Scale (PCRS; patient vs.
caregiver report) and the Self-Consciousness Scale (rating scale). All patients
underwent cognitive, psycho-affective and behavioral assessments (global
cognition, executive functions, episodic memory, anxiety-depression, and apathy
measures). RESULTS: Groups were matched for age, education, and gender. They were
comparable on the depression, anxiety, apathy and awareness scales (ps > .05),
and differed for all cognitive variables (p < .05). Using the median split
approach, greater apathy and lower depression were associated with poorer
awareness on the Self-Consciousness Scale (respectively: odds ratio [OR] = 4.8, p
= .03; OR = 4.84, p = .04), and the PCRS (only apathy: OR = 9.3, p = .003).
Greater apathy plus lower depression were associated with poorer awareness in
both scales (PCRS: OR = 40.5, p = .005; Self-consciousness scale: OR = 28, p =
.012). CONCLUSION: These results evidence comparable awareness between AD and MCI
patients. The correlates were more affective and behavioral than cognitive,
independently from assessment method.
PMID- 28413711
TI - High-throughput sequencing revealed a novel SETX mutation in a Hungarian patient
with amyotrophic lateral sclerosis.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
characterized by the degeneration of the motor neurons. To date, 126 genes have
been implicated in ALS. Therefore, the heterogenous genetic background of ALS
requires comprehensive genetic investigative approaches. METHODS: In this study,
DNA from 28 Hungarian ALS patients was subjected to targeted high-throughput
sequencing of the coding regions of three Mendelian ALS genes: FUS, SETX, and
C9ORF72. RESULTS: A novel heterozygous missense mutation (c.791A>G, p.N264S) of
the SETX gene was identified in a female patient presenting an atypical ALS
phenotype, including adult onset and lower motor neuron impairment. No further
mutations were detected in the other Mendelian ALS genes investigated.
CONCLUSION: Our study contributes to the understanding of the genetic and
phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest
that the elucidation of the genetic background of MNDs requires a complex
approach, including the screening of both Mendelian and non-Mendelian genes.
PMID- 28413712
TI - Variation within MBP gene predicts disease course in multiple sclerosis.
AB - OBJECTIVE: Prognosis following a first demyelinating event is difficult to
predict, with no genetic markers of MS progression currently identified. Myelin
basic protein (MBP) is a major component of the myelin sheath of CNS neurons and
may play a central role in demyelinating diseases such as MS. However, genetic
variation in MBP has not been implicated in MS onset risk in large genome-wide
association studies. We hypothesized that genetic variations in MBP may be a
determinant of MS clinical course. MATERIALS AND METHODS: We investigated whether
variations in the MBP gene altered clinical course (conversion to MS and/or
relapse, and annualized change in disability), using a prospectively collected
longitudinal cohort study of 127 persons who had had a first demyelinating event,
followed up to the 5-year review. RESULTS: We found one variant, rs12959006,
predicted worse clinical outcomes. The risk genotype (CT + TT) was significantly
associated with hazard of relapse (HR = 1.74, 95% CI = 1.19-2.56, p = .005) and
of greater annualized disability progression (beta = 0.18, 95% CI = 0.06-0.30, p
= .004). We also found a significant interaction between the risk genotype and
baseline anti-HHV6 IgG in predicting MS (pinteraction = 0.05) and relapse
(pinteraction = 0.02). Functional prediction analysis showed this variant is the
target of many transcription factors and the binding sites of miR-218 and miR-188
3p. CONCLUSIONS: Our results provide novel insights into the role of genetic
variation within the MBP gene predicting MS clinical course, both directly and by
interaction with known environmental MS risk factors.
PMID- 28413713
TI - Catastrophic outcome of patients with a rebound after Natalizumab treatment
discontinuation.
AB - INTRODUCTION: Natalizumab (NTZ) is an effective drug for the treatment of
relapsing-remitting multiple sclerosis. In some patients discontinuation is
mandatory due to the risk of progressive multifocal leukoencephalopathy. However,
severe clinical and radiological worsening has been described after drug
cessation. Our aim was to describe the clinical and radiological features of the
rebound phenomenon. MATERIAL AND METHODS: Patients switched from NTZ to
Fingolimod (FTY) who had presented a rebound after discontinuation were selected.
Clinical and magnetic resonance imaging (MRI) data were collected. RESULTS: Four
JC virus positive patients were included. The mean disease duration was 9.5 years
(SD: 4.12) with a mean time of 3.1 years on NTZ. All patients started FTY within
3-4 months. Neurological deterioration started in a mean time of 3.5 months (SD:
2.08) with multifocal involvement: 75% motor disturbances, 50% cognitive
impairment, 25% seizures. The average worsening in Expanded Disability Status
Scale [EDSS] was of 3.25 points (SD: 2.33). The MRI showed a very large increase
in T2 and gadolinium-enhanced lesions (mean: 23.67, SD: 18.58). All patients
received 5 days of IV methylprednisolone, one patient required plasma exchange.
All the patients presented neurological deterioration with an EDSS worsening of
1.13 points (SD: 0.48). After the rebound three patients continued treatment with
FTY, only one patient restarted NTZ. CONCLUSION: Discontinuation of NTZ treatment
may trigger a severe rebound with marked clinical and radiological worsening. A
very careful evaluation of benefit-risk should be considered before NTZ
withdrawal, and a close monitoring and a short washout period is recommended
after drug withdrawal.
PMID- 28413714
TI - Cerebrospinal fluid and plasma beta-endorphin levels in children with cerebral
malaria.
AB - OBJECTIVES: Cerebral malaria (CM) is the most lethal form of malaria, yet its
pathogenesis is not fully understood. Cytoadherence, sequestration, alterations
in cytokine expression, inflammation, and microvascular obstruction are all
hypothesized to be important in the aetio-pathogenesis of coma which
characterizes cerebral malaria and the death which sometimes result. Beta (beta)
endorphin has been postulated to be involved in the pathogenetic processes of
inflammation and cytokine expression, although the exact role is unknown. The aim
of this study was to determine the levels of beta-endorphin in cerebrospinal
fluid (CSF) and plasma of children with CM and compare the levels of beta
endorphin in the plasma of children with CM with that of apparently healthy age-
and sex-matched controls at Ile-Ife, Nigeria. MATERIALS AND METHODS: Additional
to the standard investigation for CM, CSF and venous blood samples were obtained
from the subjects for the determination of beta-endorphin levels. RESULTS: Forty
children with CM were studied along with forty age- and sex-matched controls. The
mean CSF beta-endorphin (+/- SD) level for the children with CM was 1.8 +/- 0.9
pmol/L. The mean plasma beta-endorphin levels at admission (3.1 +/- 2.0 pmol/L)
and discharge (4.1 +/- 3.3 pmol/L) were higher in children with CM than in the
control subjects (2.7 +/- 0.7 pmol/L). However, only the mean plasma beta
endorphin levels at discharge was significantly higher than that of controls (p =
.012). CONCLUSION: Children with CM had higher mean plasma beta-endorphin levels
compared to the controls and there was increased production of beta-endorphins in
children with CM during the course of the illness.
PMID- 28413715
TI - Brain serotonin 4 receptor binding is inversely associated with verbal memory
recall.
AB - BACKGROUND: We have previously identified an inverse relationship between
cerebral serotonin 4 receptor (5-HT 4R) binding and nonaffective episodic memory
in healthy individuals. Here, we investigate in a novel sample if the association
is related to affective components of memory, by examining the association
between cerebral 5-HT 4R binding and affective verbal memory recall. METHODS:
Twenty-four healthy volunteers were scanned with the 5-HT 4R radioligand
[11C]SB207145 and positron emission tomography, and were tested with the Verbal
Affective Memory Test-24. The association between 5-HT 4R binding and affective
verbal memory was evaluated using a linear latent variable structural equation
model. RESULTS: We observed a significant inverse association across all regions
between 5-HT 4R binding and affective verbal memory performances for positive (p
= 5.5 * 10-4) and neutral (p = .004) word recall, and an inverse but
nonsignificant association for negative (p = .07) word recall. Differences in the
associations with 5-HT 4R binding between word categories (i.e., positive,
negative, and neutral) did not reach statistical significance. CONCLUSION: Our
findings replicate our previous observation of a negative association between 5
HT 4R binding and memory performance in an independent cohort and provide novel
evidence linking 5-HT 4R binding, as a biomarker for synaptic 5-HT levels, to the
mnestic processing of positive and neutral word stimuli in healthy humans.
PMID- 28413716
TI - Data-driven regions of interest for longitudinal change in three variants of
frontotemporal lobar degeneration.
AB - INTRODUCTION: Longitudinal imaging of neurodegenerative disorders is a
potentially powerful biomarker for use in clinical trials. In Alzheimer's
disease, studies have demonstrated that empirically derived regions of interest
(ROIs) can provide more reliable measurement of disease progression compared with
anatomically defined ROIs. METHODS: We set out to derive ROIs with optimal effect
size for quantifying longitudinal change in a hypothetical clinical trial by
comparing atrophy rates in 44 patients with behavioral variant of frontotemporal
dementia (bvFTD), 30 with the semantic variant primary progressive aphasia
(svPPA), and 26 with the nonfluent variant PPA (nfvPPA) to atrophy in 97
cognitively healthy controls. RESULTS: The regions identified for each variant
were generally what would be expected from prior studies of frontotemporal lobar
degeneration (FTLD). Sample size estimates for detecting a 40% reduction in
annual rate of ROI atrophy varied substantially across groups, being 103 per arm
in bvFTD, 31 in nfvPPA, and 10 in svPPA, but in all groups were less than those
estimated for a priori ROIs and clinical measures. The variability in location of
peak regions of atrophy across individuals was highest in bvFTD and lowest in
svPPA, likely relating to the differences in effect size. CONCLUSIONS: These
findings suggest that, while cross-validated maps of change can improve
sensitivity to change in FTLD compared with a priori regions, the reliability of
these maps differs considerably across syndromes. Future studies can utilize
these maps to design clinical trials, and should try to identify factors
accounting for the variability in patterns of atrophy across individuals,
particularly those with bvFTD.
PMID- 28413717
TI - Advances of CD19-directed chimeric antigen receptor-modified T cells in
refractory/relapsed acute lymphoblastic leukemia.
AB - Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a
significant cause of cancer-associated morbidity and mortality for children and
adults. Developing novel and effective molecular-targeted approaches is thus a
major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one
of the most promising targeted immunotherapies, has drawn extensive attention and
resulted in multiple applications. According to published studies, CD19-directed
CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both
children and adults with refractory/relapsed ALL, much higher than that of
chemotherapy. However, the encouraging outcomes are often associated with
complications such as cytokine release syndrome (CRS), serious neurotoxicity, and
on-target off-tumor effect, which seriously impeded further clinical application
of CAR-T cells. Moreover, CAR-T therapy is typically associated with high relapse
rate. This article briefly reviews the manufacture technologies, the conditioning
regimens, the cell infusion doses, as well as the prevention and treatment
strategies of complications for CAR-T cell therapy.
PMID- 28413718
TI - Best Practices for Medication Utilization Evaluations in Postsurgical Pain
Management.
AB - PURPOSE: The purpose of this review is to provide guidance that aids in the
practical design, implementation, and analysis of medication use evaluations
(MUEs) for postsurgical pain management. SUMMARY: Clinicians have long employed
drug use evaluations or drug utilization reviews to ensure the safe and
appropriate use of medications in a hospital, medical practice, or other
healthcare setting. Although these approaches are valuable, there is a growing
trend toward replacing these methods with the MUE, a performance improvement tool
that focuses on assessing and improving medication use processes or medication
treatment response with the goal of optimizing patient outcomes. Utilizing MUEs
to assess patient outcomes and quality of life can be challenging in certain
therapeutic areas such as pain management, where measurements of pain can be
quantitative but are inherently subjective. Currently, there is little guidance
on the development of MUEs that balance subjective and objective outcomes.
CONCLUSION: MUEs continue to become the standard for quality improvement for
optimizing care and ensuring optimal outcomes. This review of the literature
provides guidance in post-surgical pain management, an area that requires
measurement of both subjective and objective outcomes.
PMID- 28413719
TI - Intra-specific variation and allometry of the skull of Late Cretaceous side
necked turtle Bauruemys elegans (Pleurodira, Podocnemididae) and how to deal with
morphometric data in fossil vertebrates.
AB - BACKGROUND: Previous quantitative studies on Bauruemys elegans (Suarez, 1969)
shell variation, as well as the taphonomic interpretation of its type locality,
have suggested that all specimens collected in this locality may have belonged to
the same population. We rely on this hypothesis in a morphometric study of the
skull. Also, we tentatively assessed the eating preference habits differentiation
that might be explained as due to ontogenetic changes. METHODS: We carried out an
ANOVA testing 29 linear measurements from 21 skulls of B. elegans taken by using
a caliper and through images, using the ImageJ software. First, a Principal
Components Analysis (PCA) was performed with 27 measurements (excluding total
length and width characters; =raw data) in order to visualize the scatter plots
based on the form variance only. Then, a second PCA was carried out using ratios
of length and width of each original measurement to assess shape variation among
individuals. Finally, original measurements were log-transformed to describe
allometries over ontogeny. RESULTS: No statistical differences were found between
caliper and ImageJ measurements. The first three PCs of the PCA with raw data
comprised 70.2% of the variance. PC1 was related to size variation and all others
related to shape variation. Two specimens plotted outside the 95% ellipse in
PC1~PC2 axes. The first three PCs of the PCA with ratios comprised 64% of the
variance. When considering PC1~PC2, all specimens plotted inside the 95% ellipse.
In allometric analysis, five measurements were positively allometric, 19 were
negatively allometric and three represented enantiometric allometry. Many bones
of the posterior and the lateral emarginations lengthen due to increasing size,
while jugal and the quadratojugal decrease in width. DISCUSSION: ImageJ is useful
in replacing caliper since there was no statistical differences. Yet iterative
imputation is more appropriate to deal with missing data in PCA. Some specimens
show small differences in form and shape. Form differences were interpreted as
occuring due to ontogeny, whereas shape differences are related to feeding
changes during growth. Moreover, all outlier specimens are crushed and/or
distorted, thus the form/shape differences may be partially due to taphonomy. The
allometric lengthening of the parietal, quadrate, squamosal, maxilla, associated
with the narrowing of jugal and quadratojugal may be related to changes in
feeding habit between different stages of development. This change in shape might
represent a progressive skull stretching and enlargement of posterior and lateral
emargination during ontogeny, and consequently, the increment of the feeding
apparatus musculature. Smaller individuals may have fed on softer diet, whereas
larger ones probably have had a harder diet, as seen in some living species of
Podocnemis. We conclude that the skull variation might be related to differences
in feeding habits over ontogeny in B. elegans.
PMID- 28413720
TI - Direct imaging of APP proteolysis in living cells.
AB - Alzheimer's disease is a multifactorial disorder caused by the interaction of
genetic, epigenetic and environmental factors. The formation of cytotoxic
oligomers consisting of Abeta peptide is widely accepted as being one of the main
key events triggering the development of Alzheimer's disease. Abeta peptide
production results from the specific proteolytic processing of the amyloid
precursor protein (APP). Deciphering the factors governing the activity of the
secretases responsible for the cleavage of APP is still a critical issue. Kits
available commercially measure the enzymatic activity of the secretases from
cells lysates, in vitro. By contrast, we have developed a prototypal rapid
bioassay that provides visible information on the proteolytic processing of APP
directly in living cells. APP was fused to a monomeric variant of the green
fluorescent protein and a monomeric variant of the red fluorescent protein at the
C-terminal and N-terminal (mChAPPmGFP), respectively. Changes in the proteolytic
processing rate in transfected human neuroblastoma and rat neuronal cells were
imaged with confocal microscopy as changes in the red/green fluorescence
intensity ratio. The significant decrease in the mean red/green ratio observed in
cells over-expressing the beta-secretase BACE1, or the alpha-secretase ADAM10,
fused to a monomeric blue fluorescent protein confirms that the proteolytic site
is still accessible. Specific siRNA was used to evaluate the contribution of
endogenous BACE1. Interestingly, we found that the degree of proteolytic
processing of APP is not completely homogeneous within the same single cell, and
that there is a high degree of variability between cells of the same type. We
were also able to follow with a fluorescence spectrometer the changes in the red
emission intensity of the extracellular medium when BACE1 was overexpressed. This
represents a complementary approach to fluorescence microscopy for rapidly
detecting changes in the proteolytic processing of APP in real time. In order to
allow the discrimination between the alpha- and the beta-secretase activity, we
have created a variant of mChAPPmGFP with a mutation that inhibits the alpha
secretase cleavage without perturbing the beta-secretase processing. Moreover, we
obtained a quantitatively robust estimate of the changes in the red/green ratio
for the above conditions by using a flow cytometer able to simultaneously excite
and measure the red and green fluorescence. Our novel approach lay the foundation
for a bioassay suitable to study the effect of drugs or particular conditions, to
investigate in an unbiased way the the proteolytic processing of APP in single
living cells in order, and to elucidate the causes of the variability and the
factors driving the processing of APP.
PMID- 28413721
TI - Aspects of gorgonopsian paleobiology and evolution: insights from the
basicranium, occiput, osseous labyrinth, vasculature, and neuroanatomy.
AB - Synapsida, the clade including therapsids and thus also mammals, is one of the
two major branches of amniotes. Organismal design, with modularity as a concept,
offers insights into the evolution of therapsids, a group that experienced
profound anatomical transformations throughout the past 270 Ma, eventually
leading to the evolution of the mammalian bauplan. However, the anatomy of some
therapsid groups remains obscure. Gorgonopsian braincase anatomy is poorly known
and many anatomical aspects of the brain, cranial nerves, vasculature, and
osseous labyrinth, remain unclear. We analyzed two gorgonopsian specimens,
GPIT/RE/7124 and GPIT/RE/7119, using propagation phase contrast synchrotron micro
computed tomography. The lack of fusion between many basicranial and occipital
bones in GPIT/RE/7124, which is an immature specimen, allowed us to reconstruct
its anatomy and ontogenetic sequence, in comparison with the mature GPIT/RE/7119,
in great detail. We explored the braincase and rendered various skull cavities.
Notably, we found that there is a separate ossification between what was
previously referred to as the "parasphenoid" and the basioccipital. We
reinterpreted this element as a posterior ossification of the basisphenoid: the
basipostsphenoid. Moreover, we show that the previously called "parasphenoid" is
in fact the co-ossification of the dermal parasphenoid and the endochondral
basipresphenoid. In line with previous descriptions, the anatomy of the osseous
labyrinth is rendered in detail, revealing a unique discoid morphology of the
horizontal semicircular canal, rather than toroidal, probably due to
architectural constraints of the ossification of the opisthotic and
supraoccipital. In addition, the orientation of the horizontal semicircular canal
suggests that gorgonopsians had an anteriorly tilted alert head posture. The
morphology of the brain endocast is in accordance with the more reptilian
endocast shape of other non-mammaliaform neotherapsids.
PMID- 28413722
TI - Performance of interferon-gamma release assay in the diagnosis of tuberculous
lymphadenitis: a meta-analysis.
AB - BACKGROUND: The diagnostic values of interferon-gamma release assays (IGRA) in
tuberculosis (TB) vary a lot with different site of infections, with especially
higher sensitivities in chronic forms of TB such as tuberculosis of the lymph
node. We conducted a meta-analysis to comprehensively evaluate the overall
accuracy of diagnostic IGRA for tuberculous lymphadenitis. METHODS: Pubmed, Web
of Science, EMBASE, Wanfang and CNKI databases up to February 17, 2017 were
searched to identify published studies. The study quality was evaluated using the
QUADAS-2 checklist. The pooled estimates of diagnostic parameters were generated
using a bivariate random-effects model and summary receiver operating
characteristic (SROC) curves were used to summarize global performance. RESULTS:
A total of ten qualified studies, performed in Korea or China, including 1,084
patients, were enrolled in this meta-analysis. The pooled estimates of diagnostic
accuracy were as follows: sensitivity, 0.89 (95% CI [0.85-0.92]); specificity,
0.81 (95% CI [0.77-0.83]); positive likelihood ratio (PLR), 4.25 (95% CI [2.79
6.47]); negative likelihood ratio (NLR), 0.16 (95% CI [0.12-0.22]); and area
under the curve (AUC) was 0.93. According to subgroup analyses, studies conducted
using QuantiFERON-TB, in Korean population and focusing on cervical lymphadenitis
exhibited relative higher specificity while lower sensitivity. No evidence of
publication bias was identified. CONCLUSIONS: IGRA exhibits high diagnostic
accuracy in tuberculous lymphadenitis. The diagnostic value of IGRA differed by
different IGRA methods, ethnicity and lymphadenitis location. Our conclusion may
be more applicable to population from TB prevalent areas.
PMID- 28413723
TI - Physiological effects of five different marine natural organic matters (NOMs) and
three different metals (Cu, Pb, Zn) on early life stages of the blue mussel
(Mytilus galloprovincialis).
AB - Metals are present in aquatic environments as a result of natural and
anthropogenic inputs, and may induce toxicity to organisms. One of the main
factors that influence this toxicity in fresh water is natural organic matter
(NOM) but all NOMs are not the same in this regard. In sea water, possible
protection by marine NOMs is not well understood. Thus, our study isolated marine
NOMs by solid-phase extraction from five different sites and characterized them
by excitation-emission fluorescence analysis-one inshore (terrigenous origin),
two offshore (autochthonous origin), and two intermediate in composition
(indicative of a mixed origin). The physiological effects of these five NOMS
alone (at 8 mg/L), of three metals alone (copper, lead and zinc at 6 ug Cu/L, 20
ug Pb/L, and 25 ug Zn/L respectively), and of each metal in combination with each
NOM, were evaluated in 48-h exposures of mussel larvae. Endpoints were whole body
Ca2++Mg2+-ATPase activity, carbonic anhydrase activity and lipid peroxidation. By
themselves, NOMs increased lipid peroxidation, Ca2++Mg2+-ATPase, and/or carbonic
anhydrase activities (significant in seven of 15 NOM-endpoint combinations),
whereas metals by themselves did not affect the first two endpoints, but Cu and
Pb increased carbonic anhydrase activities. In combination, the effects of NOMs
predominated, with the metal exerting no additional effect in 33 out of 45
combinations. While NOM effects varied amongst different isolates, there was no
clear pattern with respect to optical or chemical properties. When NOMs were
treated as a single source by data averaging, NOM had no effect on Ca2++Mg2+
ATPase activity but markedly stimulated carbonic anhydrase activity and lipid
peroxidation, and there were no additional effects of any metal. Our results
indicate that marine NOMs may have direct effects on this model marine organism,
as well as protective effects against metal toxicity, and the quality of marine
NOMs may be an important factor in these actions.
PMID- 28413724
TI - Are anti-ganglioside antibodies associated with proventricular dilatation disease
in birds?
AB - The identification of Parrot bornaviruses (PaBV) in psittacine birds with
proventricular dilatation disease (PDD) has not been sufficient to explain the
pathogenesis of this fatal disease, since not all infected birds develop clinical
signs. Although the most accepted theory indicates that PaBV directly triggers an
inflammatory response in this disease, another hypothesis suggests the disease is
triggered by autoantibodies targeting neuronal gangliosides, and PDD might
therefore resemble Guillain-Barre Syndrome (GBS) in its pathogenesis.
Experimental inoculation of pure gangliosides and brain-derived ganglioside
extracts were used in two different immunization studies. The first study was
performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were
inoculated with a brain ganglioside extract in Freund's complete adjuvant (FCA)
and six chickens inoculated with phosphate-buffered saline. A second study was
performed five healthy quaker parrots (Myiopsitta monachus) that were divided
into three groups: Two quaker parrots received purified gangliosides in FCA, two
received a crude brain extract in FCA, and one control quaker parrot received FCA
alone. One chicken developed difficult in walking. Histologically, only a mild
perivascular and perineural lymphocytic infiltrate in the proventriculus. Two
quaker parrots (one from each treatment group) had mild lymphoplasmacytic
encephalitis and myelitis. However, none of the quaker parrots developed
myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in
birds are not associated with a condition resembling PDD.
PMID- 28413726
TI - gb4gv: a genome browser for geminivirus.
AB - BACKGROUND: Geminiviruses (family Geminiviridae) are prevalent plant viruses that
imperil agriculture globally, causing serious damage to the livelihood of
farmers, particularly in developing countries. The virus evolves rapidly,
attributing to its single-stranded genome propensity, resulting in worldwide
circulation of diverse and viable genomes. Genomics is a prominent approach taken
by researchers in elucidating the infectious mechanism of the virus. Currently,
the NCBI Viral Genome website is a popular repository of viral genomes that
conveniently provides researchers a centralized data source of genomic
information. However, unlike the genome of living organisms, viral genomes most
often maintain peculiar characteristics that fit into no single genome
architecture. By imposing a unified annotation scheme on the myriad of viral
genomes may downplay their hallmark features. For example, the viron of
begomoviruses prevailing in America encapsulates two similar-sized circular DNA
components and both are required for systemic infection of plants. However, the
bipartite components are kept separately in NCBI as individual genomes with no
explicit association in linking them. Thus, our goal is to build a comprehensive
Geminivirus genomics database, namely gb4gv, that not only preserves genomic
characteristics of the virus, but also supplements biologically relevant
annotations that help to interrogate this virus, for example, the targeted host,
putative iterons, siRNA targets, etc. METHODS: We have employed manual and
automatic methods to curate 508 genomes from four major genera of Geminiviridae,
and 161 associated satellites obtained from NCBI RefSeq and PubMed databases.
RESULTS: These data are available for free access without registration from our
website. Besides genomic content, our website provides visualization capability
inherited from UCSC Genome Browser. DISCUSSION: With the genomic information
readily accessible, we hope that our database will inspire researchers in gaining
a better understanding of the incredible degree of diversity of these viruses,
and of the complex relationships within and between the different genera in the
Geminiviridae. AVAILABILITY AND IMPLEMENTATION: The database can be found at:
http://gb4gv.lafayette.edu.
PMID- 28413725
TI - Trypanosoma cruzi reservoir-triatomine vector co-occurrence networks reveal meta
community effects by synanthropic mammals on geographic dispersal.
AB - Contemporary patterns of land use and global climate change are modifying
regional pools of parasite host species. The impact of host community changes on
human disease risk, however, is difficult to assess due to a lack of information
about zoonotic parasite host assemblages. We have used a recently developed
method to infer parasite-host interactions for Chagas Disease (CD) from vector
host co-occurrence networks. Vector-host networks were constructed to analyze
topological characteristics of the network and ecological traits of species'
nodes, which could provide information regarding parasite regional dispersal in
Mexico. Twenty-eight triatomine species (vectors) and 396 mammal species
(potential hosts) were included using a data-mining approach to develop models to
infer most-likely interactions. The final network contained 1,576 links which
were analyzed to calculate centrality, connectivity, and modularity. The model
predicted links of independently registered Trypanosoma cruzi hosts, which
correlated with the degree of parasite-vector co-occurrence. Wiring patterns
differed according to node location, while edge density was greater in
Neotropical as compared to Nearctic regions. Vectors with greatest public health
importance (i.e., Triatoma dimidiata, T. barberi, T. pallidipennis, T.
longipennis, etc), did not have stronger links with particular host species,
although they had a greater frequency of significant links. In contrast, hosts
classified as important based on network properties were synanthropic mammals.
The latter were the most common parasite hosts and are likely bridge species
between these communities, thereby integrating meta-community scenarios
beneficial for long-range parasite dispersal. This was particularly true for
rodents, >50% of species are synanthropic and more than 20% have been identified
as T. cruzi hosts. In addition to predicting potential host species using the co
occurrence networks, they reveal regions with greater expected parasite mobility.
The Neotropical region, which includes the Mexican south and southeast, and the
Transvolcanic belt, had greatest potential active T. cruzi dispersal, as well as
greatest edge density. This information could be directly applied for
stratification of transmission risk and to design and analyze human-infected
vector contact intervention efficacy.
PMID- 28413727
TI - A transdisciplinary approach to the initial validation of a single cell protein
as an alternative protein source for use in aquafeeds.
AB - The human population is growing and, globally, we must meet the challenge of
increased protein needs required to feed this population. Single cell proteins
(SCP), when coupled to aquaculture production, offer a means to ensure future
protein needs can be met without direct competition with food for people. To
demonstrate a given type of SCP has potential as a protein source for use in
aquaculture feed, a number of steps need to be validated including demonstrating
that the SCP is accepted by the species in question, leads to equivalent survival
and growth, does not result in illness or other maladies, is palatable to the
consumer, is cost effective to produce and can easily be incorporated into diets
using existing technology. Here we examine white shrimp (Litopenaeus vannamei)
growth and consumer taste preference, smallmouth grunt (Haemulon chrysargyreum)
growth, survival, health and gut microbiota, and Atlantic salmon (Salmo salar)
digestibility when fed diets that substitute the bacterium Methylobacterium
extorquens at a level of 30% (grunts), 100% (shrimp), or 55% (salmon) of the
fishmeal in a compound feed. In each of these tests, animals performed
equivalently when fed diets containing M. extorquens as when fed a standard
aquaculture diet. This transdisciplinary approach is a first validation of this
bacterium as a potential SCP protein substitute in aquafeeds. Given the ease to
produce this SCP through an aerobic fermentation process, the broad applicability
for use in aquaculture indicates the promise of M. extorquens in leading toward
greater food security in the future.
PMID- 28413729
TI - Elucidating the diet of the island flying fox (Pteropus hypomelanus) in
Peninsular Malaysia through Illumina Next-Generation Sequencing.
AB - There is an urgent need to identify and understand the ecosystem services of
pollination and seed dispersal provided by threatened mammals such as flying
foxes. The first step towards this is to obtain comprehensive data on their diet.
However, the volant and nocturnal nature of bats presents a particularly
challenging situation, and conventional microhistological approaches to studying
their diet can be laborious and time-consuming, and provide incomplete
information. We used Illumina Next-Generation Sequencing (NGS) as a novel, non
invasive method for analysing the diet of the island flying fox (Pteropus
hypomelanus) on Tioman Island, Peninsular Malaysia. Through DNA metabarcoding of
plants in flying fox droppings, using primers targeting the rbcL gene, we
identified at least 29 Operationally Taxonomic Units (OTUs) comprising the diet
of this giant pteropodid. OTU sequences matched at least four genera and 14 plant
families from online reference databases based on a conservative Least Common
Ancestor approach, and eight species from our site-specific plant reference
collection. NGS was just as successful as conventional microhistological analysis
in detecting plant taxa from droppings, but also uncovered six additional plant
taxa. The island flying fox's diet appeared to be dominated by figs (Ficus sp.),
which was the most abundant plant taxon detected in the droppings every single
month. Our study has shown that NGS can add value to the conventional
microhistological approach in identifying food plant species from flying fox
droppings. At this point in time, more accurate genus- and species-level
identification of OTUs not only requires support from databases with more
representative sequences of relevant plant DNA, but probably necessitates in situ
collection of plant specimens to create a reference collection. Although this
method cannot be used to quantify true abundance or proportion of plant species,
nor plant parts consumed, it ultimately provides a very important first step
towards identifying plant taxa and spatio-temporal patterns in flying fox diets.
PMID- 28413728
TI - Mechanism of endothelial nitric oxide synthase phosphorylation and activation by
tentacle extract from the jellyfish Cyanea capillata.
AB - Our previous study demonstrated that tentacle extract (TE) from the jellyfish
Cyanea capillata (C. capillata) could cause a weak relaxation response mediated
by nitric oxide (NO) using isolated aorta rings. However, the intracellular
mechanisms of TE-induced vasodilation remain unclear. Thus, this study was
conducted to examine the role of TE on Akt/eNOS/NO and Ca2+ signaling pathways in
human umbilical vein endothelial cells (HUVECs). Our results showed that TE
induced dose- and time-dependent increases of eNOS activity and NO production.
And TE also induced Akt and eNOS phosphorylation in HUVECs. However, treatment
with specific PI3-kinase inhibitor (Wortmannin) significantly inhibited the
increases in NO production and Akt/eNOS phosphorylation. In addition, TE also
stimulated an increase in the intracellular Ca2+ concentration ([Ca2+]i), which
was significantly attenuated by either IP3 receptor blocker (Heparin) or PKC
inhibitor (PKC 412). In contrast, extracellular Ca2+-free, L-type calcium channel
blocker (Nifedipine), or PKA inhibitor (H89) had no influence on the [Ca2+]i
elevation. Since calcium ions also play a critical role in stimulating eNOS
activity, we next explored the role of Ca2+ in TE-induced Akt/eNOS activation. In
consistent with the attenuation of [Ca2+]i elevation, we found that Akt/eNOS
phosphorylation was also dramatically decreased by Heparin or PKC 412, but not
affected by Nifedipine or H89. However, the phosphorylation level could also be
decreased by the removal of extracellular calcium. Taken together, our findings
indicated that TE-induced eNOS phosphorylation and activation were mainly through
PI3K/Akt-dependent, PKC/IP3R-sensitive and Ca2+-dependent pathways.
PMID- 28413730
TI - Effects of chronic exposure to clothianidin on the earthworm Lumbricus
terrestris.
AB - Although neonicotinoids are targeted at insects, their predominant use as a seed
dressing and their long persistence in soils mean that non-target soil organisms
such as earthworms are likely to be chronically exposed to them. Chronic exposure
may pose risks that are not evaluated in most toxicity tests. We experimentally
tested the effect of field-realistic concentrations of a commonly used
neonicotinoid, clothianidin, on mortality, weight gain, and food consumption to
assess the impacts of chronic exposure over four months on fitness of L.
terrestris individuals. We undertook three separate experiments, each with
different exposure routes: treated soil only (experiment A), treated food and
soil combined (experiment B) and treated food only (experiment C). Mortality was
negatively affected by exposure from treated soil only with greatest mortality
observed in the groups exposed to the two highest concentrations (20 ppb and 100
ppb), but no clear effect on mortality was found in the other two experiments.
When clothianidin was present in the food, an anti-feedant effect was present in
months one and two which subsequently disappeared; if this occurs in the field,
it could result in reduced rates of decomposition of treated crop foliage. We
found no significant effects of any treatment on worm body mass. We cannot rule
out stronger adverse effects if worms come into close proximity to treated seeds,
or if other aspects of fitness were examined. Overall, our data suggest that
field-realistic exposure to clothianidin has a significant but temporary effect
on food consumption and can have weak but significant impacts on mortality of L.
terrestris.
PMID- 28413731
TI - Meloxicam ameliorates the cartilage and subchondral bone deterioration in
monoiodoacetate-induced rat osteoarthritis.
AB - OBJECTIVE: This study aimed to quantify the cartilage- and subchondral bone
related effects of low-dose and high-dose meloxicam treatment in the late phase
of mono-iodoacetate-induced osteoarthritis of the stifle. METHODS: Thirty-four
male Wistar rats received intra-articular injection of mono-iodoacetate to
trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono
iodoacetate-injected rats were assigned to three groups and treated from week 4
to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg,
n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4
additional weeks (end of week 11) the animals were sacrificed, and the stifle
joints were examined histologically and immunohistochemically for cyclooxygenase
2, in conformity with recommendations of the Osteoarthritis Research Society
International. Serum cytokines IL-6, TNFalpha and IL-10 were measured at the end
of weeks 3, 7, and 11. RESULTS: Compared with saline-treated controls, animals
treated with mono-iodoacetate developed various degrees of osteoarthritis. The
cartilage degeneration score and the total cartilage degeneration width were
significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose
(p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In
the subchondral bone, only high-dose meloxicam exerted a significant protective
effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated
animals was abolished in both meloxicam groups. Increase with borderline
significance of TNFalpha in GrpP from week 3 to week 7 (p = 0.049) and reduction
of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed. CONCLUSION:
In this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a
chondroprotective effect, and the high dose also protected against subchondral
bone lesions. The results suggest a superior protection of the high-dose
meloxicam arresting the low-grade inflammatory pathway accompanied by chronic
cartilage deterioration.
PMID- 28413732
TI - Calcification and growth rate recovery of the reef-building Pocillopora species
in the northeast tropical Pacific following an ENSO disturbance.
AB - Pocilloporids are one of the major reef-building corals in the eastern tropical
Pacific (ETP) and also the most affected by thermal stress events, mainly those
associated with El Nino/Southern Oscillation (ENSO) periods. To date, coral
growth parameters have been poorly reported in Pocillopora species in the
northeastern region of the tropical Pacific. Monthly and annual growth rates of
the three most abundant morphospecies (P. cf. verrucosa, P. cf. capitata, and P.
cf. damicornis) were evaluated during two annual periods at a site on the Pacific
coast of Mexico. The first annual period, 2010-2011 was considered a strong
ENSO/La Nina period with cool sea surface temperatures, then followed by a non
ENSO period in 2012-2013. The linear extension rate, skeletal density, and
calcification rate averaged (+/-SD) were 2.31 +/- 0.11 cm yr-1, 1.65 +/- 0.18 g
cm-3, 5.03 +/- 0.84 g cm-2 yr-1 respectively, during the strong ENSO event. In
contrast, the respective non-ENSO values were 3.50 +/- 0.64 cm yr-1, 1.70 +/-
0.18 g cm-3, and 6.02 +/- 1.36 g cm-2 yr-1. This corresponds to 52% and 20%
faster linear extension and calcification rates, respectively, during non-ENSO
period. The evidence suggests that Pocillopora branching species responded
positively with faster growth rates following thermal anomalies, which allow them
to maintain coral communities in the region.
PMID- 28413733
TI - Experimental Studies on the Hydrotreatment of Kraft Lignin to Aromatics and
Alkylphenolics Using Economically Viable Fe-Based Catalysts.
AB - Limonite, a low-cost iron ore, was investigated as a potential hydrotreatment
catalyst for kraft lignin without the use of an external solvent (batch reactor,
initial H2 pressure of 100 bar, 4 h). The best results were obtained at 450
degrees C resulting in 34 wt % of liquefied kraft lignin (lignin oil) on lignin
intake. The composition of the lignin oil was determined in detail (elemental
composition, GC-MS, GC*GC-FID, and GPC). The total GC-detectable monomeric
species amounts up to 31 wt % on lignin intake, indicating that 92 wt % of the
products in the lignin oil are volatile and thus of low molecular weight. The
lignin oil was rich in low-molecular-weight alkylphenolics (17 wt % on lignin)
and aromatics (8 wt % on lignin). Performance of the limonite catalyst was
compared to other Fe-based catalysts (goethite and iron disulfide) and limonite
was shown to give the highest yields of alkylphenolics and aromatics. The
limonite catalyst before and after reaction was characterized using XRD, TEM, and
nitrogen physisorption to determine changes in structure during reaction.
Catalyst recycling tests were performed and show that the catalyst is active
after reuse, despite the fact that the morphology changed and that the surface
area of the catalyst particles was decreased. Our results clearly reveal that
cheap limonite catalysts have the potential to be used for the
depolymerization/hydrodeoxygenation of kraft lignin for the production of
valuable biobased phenolics and aromatics.
PMID- 28413734
TI - Implantable Systems for Continuous Liquorpheresis and CSF Replacement.
AB - Liquorpheresis (cerebrospinal fluid filtration) comprises a therapeutical
approach that has been proposed to treat several neurological conditions where
antibodies, inflammatory mediators, or abnormal peptides are the cause or play an
important role in the pathogenesis of the disease. Continuous or intermittent
cerebrospinal fluid (CSF) replacement may be an alternative approach not explored
thus far. Here, we review previous experiences in the use of liquorpheresis in
autoimmune and degenerative neurological diseases. Then we describe previous
technical reports and provide some new innovations in order to design
bidirectional CSF shunting systems that can be complemented either with a deposit
of artificial CSF or with a filter of CSF, allowing CSF replacement or
liquorpheresis respectively. Both options would lead to mechanical dilution of
the patient's CSF.
PMID- 28413735
TI - A Survey of Handwashing Knowledge and Attitudes among the Healthcare
Professionals in Lahore, Pakistan.
AB - OBJECTIVE: To evaluate the knowledge and attitudes towards handwashing of
clinical year medical and dental students and health-care professionals (HCPs)
working in the departments of medicine, surgery, dentistry, nursing, and
physiotherapy in Lahore, Pakistan. METHODOLOGY: This was a cross-sectional survey
conducted during May and June 2016. After approval from the institutional review
board, a modified form of the World Health Organization (WHO) Hand Hygiene
Knowledge Questionnaire for Healthcare workers that included 18 items was sent to
400 clinical year students and HCPs from six medical colleges and affiliated
hospitals of Lahore. The data obtained was entered and analyzed by using IBM SPSS
version 20 (IBM, NY, USA). Chi-square was used as the test of significance. A p
value of <0.05 was considered statistically significant for all purposes.
RESULTS: The response rate was 79%. Less than half of the respondents (149,
47.9%) were satisfied with their knowledge regarding hand hygiene. Statistically
significant associations of various groups of HCPs were observed with their
satisfaction regarding knowledge about hand hygiene (p-value = 0.022), their
awareness of the proper technique required for handwashing proposed by the WHO (p
value = 0.001), and their awareness about other preventive techniques proposed by
the WHO and Centers for Disease Control (CDC) (p-value = 0.021). CONCLUSIONS: The
majority of the clinical year students and HCPs were not satisfied with their
knowledge regarding hand hygiene. HCPs working in different departments have
varying knowledge and attitudes towards hand hygiene. Females were found to be
more satisfied with their handwashing practices. Teaching proper technique of
handwashing to medical students and starting refresher courses regarding hand
hygiene for HCPs are dire needs. The WHO-recommended guidelines should not only
be taught but also implemented in the medical field as poor hand hygiene
techniques have led to the spread of many diseases around the globe.
PMID- 28413736
TI - Targeted Intraspinal Radiofrequency Ablation for Lumbar Spinal Stenosis.
AB - INTRODUCTION: By using a combination of magnetic resonance imaging (MRI) and
computed tomography (CT) of the lumbar spine, it is possible to distinguish
between spinal stenosis caused by bone compression and specific soft tissue
epidural intraspinal lesions that cause localized spinal canal stenosis and
neural compression. Examples include facet cysts and yellow ligament hypertrophy.
Many of these patients are elderly with medical comorbidities that make open
surgery problematic. MATERIALS & METHODS: This is a study of patients with
predominantly soft tissue stenosis being treated with targeted intraspinal
radiofrequency (RF) heat ablation. This novel procedure is performed under local
anesthesia in an outpatient setting using intra-operative imaging. Fine tip 20
gauge RF electrodes (Stryker(r) PA, USA) are precisely placed under radiologic
guidance in the identified soft tissue causing the posterior compression of the
lumbar spinal canal. After sensory and motor testing to make sure there is a safe
distance of the needle tip from the nearby nerve roots to avoid any neural
effect, multiple targeted lesions correlated by the MRI or CT scan are made in
the fibrous and cystic soft tissue. Lesions are created using a focused 2 or 5 mm
tip at 60 degrees centigrade ( degrees C) for either 30 or 60 seconds. This heat
causes sufficient shrinking of the targeted soft tissue resulting in relative
reduction of the soft tissue component of the stenosis. This relative reduction
in the stenosis of the spinal canal, similar to that measured with interspinous
devices, provides long-term relief of symptoms, signs, and improvement of spinal
motion in patients with lumbar stenosis. This report will review the spinal
anatomy, and development and history of using RF in and around the nerve roots
and epidural space, as it relates to lumbar stenosis. Examples of before and
after MRI scans demonstrate the radiologic reduction in the size of the lesions.
This soft tissue reduction correlates with patients' improvement in pain and
clinical symptoms. Follow-up of the patients up to 30 months shows that the
effect of RF heat on the soft tissue is long lasting. RESULTS: In our long-term
follow-up of greater than six months, 58% of RF treated patients had lasting
relief of clinical symptoms, back pain, and claudication with increased spinal
movement. This reduction in pain and improvement in motion allows patients to
continue more aggressive physical therapy and muscle strengthening that
secondarily can improve their symptoms. Post-procedure follow-up MRI scans in
multiple patients have shown a clear reduction in soft tissue lesion size. Long
term follow-up demonstrated that 58% of patients treated with RF targeted
ablation have not required further intervention and 22% went on to other surgical
treatments for lumbar spinal stenosis. CONCLUSION: By reducing the soft tissue
component of the stenosis with RF ablation and creating relatively more epidural
space, targeted intraspinal RF may be a possible minimally invasive, percutaneous
non-surgical alternative to treatment in a number of patients where soft tissue
lumbar stenosis is the main cause of patients' symptoms. This technique offers a
simple and safe additional method to relieve symptoms of lumbar stenosis and
possibly compression within the neural foramina, especially in the elderly.
PMID- 28413737
TI - Amino Acid (Leucine) Chromatography: A Study of Branched-Chain Aminoaciduria in
Type 2 Diabetes.
AB - INTRODUCTION: Diabetes is a disease characterized by insulin deficiency resulting
in glucose intolerance and in abnormalities of other metabolic fuels including
protein. Recently, a number of studies have revealed that branched-chain amino
acids (BCAAs) (leucine, isoleucine, and valine) play an important role in the
regulation of protein synthesis by activating mammalian target of rapamycin
(mTOR) in pancreatic beta cells. BCAAs have positive effects on the regulation of
glucose homeostasis. Leucine is an important nutrient signal as evidenced by
recent observations, which showed increased fasting concentrations of circulating
BCAAs being associated with an increased risk of type 2 diabetes (T2D) and
insulin resistance in humans. Leucine seems to have direct effects on
hypothalamic and brainstem functioning involved in satiety, which can potentially
contribute to obesity and T2D. A number of observational studies indicate that
elevated activity of BCAAs could be associated with poor metabolic health and T2D
complications. Although these associations were consistently observed in humans,
the mechanisms underlying this relationship remain to be completely understood.
In this study, we have attempted to evaluate urinary excretion of leucine among
patients of T2D and compared them with healthy controls by using a low-cost and
non-invasive amino acid chromatography technique. METHODS: The study was carried
out in the Department of Biochemistry, Central Research Unit, Prathima Institute
of Medical Sciences (PIMS), Karimnagar, Telangana, India, during the period
between July and September 2016. A group of 55 normal healthy subjects (control
group A), and 55 patients suffering from T2D on treatment (test group B), were
enrolled in the study. The urine samples were collected from normal and T2D
subjects. Thin-layer chromatography (TLC) for leucine was performed on all the
urine samples. RESULTS: A strong correlation (p=0.0004) was found between the
urinary excretion of leucine among the control (Rf=0.174 +/-0.089) and T2D
(Rf=0.247 +/-0.030) patients. CONCLUSION: Excretion of BCAAs (leucine) in
detectable and increased quantities reflect the presence of an altered metabolic
state attributable to T2D, which in turn could lead to early diabetic
complications. This method (TLC), being non-invasive and cost-effective, could be
recommended for assessing the progression and management of type 2 diabetes
patients.
PMID- 28413738
TI - High-energy Trauma Precipitating Intramedullary Cavernous Malformation Hemorrhage
- A Possible Underreported Mechanism.
AB - Cavernous malformations are uncommon vascular lesions with an estimated
prevalence of 0.5% in the general population. Intramedullary cavernous
malformations (ICM) represent a rare subset of lesions, which account for
approximately 5% of all cavernous malformations. The annual risk of hemorrhage in
ICMs has been reported to range from 1.4 to 6.8%. Most patients are diagnosed
with neurological dysfunction secondary to ICM hemorrhage and little is known
about the inciting events that lead to hemorrhage. A few studies have suggested
that minor and major trauma or even intense exertion may increase the risk of
hemorrhage. We report the case of a 62-year-old male who developed progressive
neurological deterioration following a motor vehicle accident. During work-up, an
ICM was found at T4 and was surgically removed. At his 10-month follow-up, the
patient had partially recovered, regaining motor strength in his right lower
extremity, but had a persistent decrease in temperature and pinprick sensation on
the left side starting at the T6 dermatome. We hypothesize that ICMs can rupture
after high-energy impacts, such as the motor vehicle accident in our patient, and
mechanical factors, such as trauma and stretching maneuvers, can play a role in
the pathogenesis of ICM hemorrhage.
PMID- 28413739
TI - Genetic Modulation Therapy Through Stem Cell Transplantation for Human
Immunodeficiency Virus 1 Infection.
AB - Highly active anti-retroviral treatment has changed the dimensions of the
outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired
immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment
which is spreading throughout the world extensively. Given the confinements of
the present restorative methodologies and the non-availability of any strategic
vaccination against HIV, there is a squeezing need to build a therapeutic
treatment. Viral tropism for HIV includes CD4+ cells, macrophages, and microglial
cells, and it is through binding with co-receptors C-C chemokine receptor type 5
(CCR5) and C-X-C chemokine receptor type 4 (CXCR4). While these cell types are
present in all individuals, there are rare cases that stayed uninfected even
after getting exposed to an overwhelming load of HIV. Research revealed a
homozygous 32-base pair deletion (Delta32/Delta32) in CCR5. After careful
consideration, a hypothesis was proposed a few years back that a cure for HIV
disease is possible, through hematopoietic stem cells transplantation from a
donor homozygous for the CCR5-Delta32 deletion. Hematopoietic stem cell (HSC)
based quality treatment may serve as a promising tool as these perpetual, self
renewing progenitor cells could be modified to oppose HIV infection. If done
properly, the changed HSCs would offer the permanent creation of genetically
modified cells that are resistant to HIV infection and/or have improved hostility
to viral action which will eventually clear the contaminated cells. The purpose
of this review is to concentrate on two facets of HSC genetic treatment for
potentially life-threatening HIV infection: building HIV-resistant cells and
designing cells that can target HIV disease. These two strategic approaches can
be the frontline of a quality treatment plan against HIV infection and, as an
individual treatment or a combination thereof, has been proposed to possibly
destroy HIV altogether.
PMID- 28413741
TI - Serial Magnetic Resonance Imaging in Creutzfeldt-Jakob Disease: a Case Report and
Literature Review.
AB - Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain
disorder. CJD usually appears in later life and runs a rapid course. Typically,
the onset of symptoms occurs about age 60 and about 90% of individuals die within
one year. We report a case of 67-year-old male presented with progressive
aphasia, confusion, dysphagia and inability to carry out activities of daily life
(ADLs) over a period of three to four weeks. The patient had past medical history
of chronic atrial fibrillation and hypertension. Prior to admission, the patient
was treated for ischemic stroke of left basal ganglia but continued to have
worsening encephalopathy. The spinal tap revealed a 14-3-3 protein level of
thirteen times the upper limit of normal; electroencephalogram (EEG) showed a
diffuse slowing of the background and periodic sharp waves with greater
involvement of the left hemisphere. Diffusion-weighted imaging (DWI) magnetic
resonance imaging (MRI) at the time of admission showed extensive signal
abnormality in the basal ganglia bilaterally and in the cerebral cortex
bilaterally, particularly over the left cerebral hemisphere. The persistence of
the MRI findings over several weeks was concerning for spongiform encephalopathy.
The probable diagnosis of Creutzfeldt-Jakob disease was made based on these
imaging findings taken together with the patient's clinical signs and symptoms of
a rapidly progressive encephalopathy. The patient was able to have some quality
time with his family as the diagnosis was made earlier than perhaps otherwise and
expired peacefully after comfort care measures were chosen. Serial MRI may serve
as a clue to the early diagnosis of CJD and potentially provide a better quality
of life for the patients.
PMID- 28413740
TI - Relationship of the Median and Radial Nerves at the Elbow: Application to
Avoiding Injury During Venipuncture or Other Invasive Procedures of the Cubital
Fossa.
AB - INTRODUCTION: The median and radial nerves are two important neural structures
found in the cubital fossa. The trajectory and landmarks used to identify their
location are important when procedures are done in this area. METHODS AND
MATERIALS: Ten fresh-frozen cadavers were dissected (20 upper limbs) and
measurements were taken from the medial epicondyle to the median and radial
nerves as well as to the lateral epicondyle of each limb. RESULTS: The distance
between the medial epicondyle and the median nerve was found to be three
centimeters with a range of 2.1 to four centimeters and the distance from the
medial epicondyle to the radial nerve had a mean distance of 5.5 cm and a range
of 3.8 to seven centimeters. DISCUSSION: Damage to the median or radial nerves
can lead to major complications including loss of extension, flexion, and
sensation in the forearm and hand. Other studies have tried to identify the
course of these nerves in order to prevent their injury during procedures.
CONCLUSION: After identifying the medial epicondyle, using the results we
obtained, physicians may have a better understanding of where the median and
radial nerves lie within the cubital fossa when performing procedures in this
area.
PMID- 28413742
TI - Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute
Leukemia.
AB - Myelodysplastic syndrome (MDS) refers to a group of various stem cell disorders,
characterized by dysplastic and ineffective production in one or more cell lines.
In general, MDS tends to present slowly over months to years and is commonly
detected with routine bloodwork by primary care physicians. Patients may be
asymptomatic and depending on age, comorbidities and risk classification of MDS
may not require aggressive therapy. However, MDS carries the risk of progressing
to acute leukemia over time. We present a case of rapidly progressive MDS in a
previously healthy middle-aged female, originally presenting and treated as acute
leukemia.
PMID- 28413743
TI - Real-Time Fluoroscopic and C-Arm Computed Tomography Evaluation of Ommaya
Reservoir Integrity.
AB - We describe a case of a 24-year-old patient with relapsed acute myelogenous
leukemia involving the central nervous system. After placement of an Ommaya
reservoir for intrathecal chemotherapy administration, the patient developed
progressive headache, nausea, and drowsiness and was found to have an enlarging
subdural collection underlying the Ommaya. To exclude leakage of the Ommaya
system into the subdural space, real-time fluoroscopic and C-arm computed
tomographic evaluation of the Ommaya reservoir was performed after iodinated
contrast injection into the reservoir. This novel technique demonstrated complete
integrity of the Ommaya reservoir without evidence of blockage or leakage of the
system. The patient underwent uncomplicated evacuation of the subdural collection
without replacement of the Ommaya reservoir and made an excellent recovery. This
technique for real-time interrogation of the Ommaya reservoir may have additional
utility in the evaluation for Ommaya reservoir dysfunction.
PMID- 28413744
TI - Bilateral Retinal Detachments Associated with Inversion Table Therapy.
AB - To report a case of sequential bilateral inferior retinal detachments secondary
to inversion table therapy. A 67-year-old-male developed inferior rhegmatoegnous
retinal detachments (RRD) in both eyes on two different occasions with the use of
inversion therapeutic tables. Various predisposing factors have been documented
for RRD such as previous cataract surgery, peripheral retinal degenerations, high
myopia, history of previous retinal detachments and direct ocular trauma. The
authors report here a case of inferior retinal detachments associated with the
use of inversion therapy. Physical therapists, physical medicine rehabilitation
physicians, and retinal specialists need be aware of this potential complication.
PMID- 28413746
TI - Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective
Matrix Metalloproteinase Inhibitor.
AB - Invited for this month's cover picture is the group of Professor Rainer Riedl
from the Institute of Chemistry and Biotechnology at the Zurich University of
Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure
based design of a drug-like small molecule inhibitor of matrix metalloproteinase
13 (MMP-13) with a combined dual binding motif. The targeted introduction of a
single fluoro atom was of vital importance for the optimization of the inhibitor.
For more details, read the full text of the Communication at
10.1002/open.201600158.
PMID- 28413745
TI - Seven Cases of Zika Virus Infection in South Florida.
AB - INTRODUCTION: Zika virus, an arbovirus of the Flaviviridae family, is a mosquito
borne virus known to cause microcephaly through vertical transmission. Infection
presents with mild, self-limiting symptoms. Currently, a Zika virus outbreak has
spread across most of South and Central America. Travel-related and sexually
transmitted cases have been reported across the United States. However, the
vector-borne transmission has been limited to Florida and Texas. We present seven
cases of Zika virus infection that presented at a single institution in South
Florida. METHODS: Patients were included that had real-time polymerase-chain
reaction (RT-PCR) for Zika virus RNA in urine or serum or enzyme-linked
immunosorbent assay (ELISA) for Immunoglobulin M (IgM) antibody against Zika
virus in serum. RESULTS: All seven patients reported recent travel or employment
in areas of active Zika virus transmission and at least two of the four most
commonly reported symptoms (fever, arthralgia, rash, and conjunctivitis) with a
rash present in all patients. All patients had positive RT-PCR for Zika virus RNA
in urine. RT-PCR for Zika virus RNA in serum was negative in four of five
patients that were tested, indicating that these patients likely presented one to
two weeks after symptom onset. CONCLUSION: The future of Zika virus outbreaks in
other cities in the United States is still uncertain. However, it is clear that
prevention and control policies are urgently needed. We have presented seven
confirmed cases of Zika virus infection in South Florida. In addition to
conducting research concerning both the diagnostic and therapeutic aspects of the
virus, there is a need for public awareness of its presentation, methods of
transmission, and subsequent clinical outcomes.
PMID- 28413747
TI - Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry.
AB - Tetrahydropyranyl (Thp) is recognized as a useful protecting group for alcohols
in organic synthesis. It has several advantages, including low cost, ease of
introduction, general stability to most non-acidic reagents, it confers good
solubility, and the ease with which it can be removed if the functional group it
protects requires manipulation. However, little attention has been paid to Thp in
peptide chemistry. Provided here is a concise analysis of the Thp protection of
various amino acid functionalities (OH, SH, NH and COOH) and its application to
peptide synthesis. Thp is a useful moiety for the side-chain protection of
serine, threonine and cysteine and is suitable for the Fmoc/tBu solid-phase
peptide synthesis strategy. The immobilized version of 3,4-dihydro-2H-pyran, the
so-called Ellman resin, is also discussed as a useful solid support for anchoring
the side chains of serine, threonine and tryptophan residues.
PMID- 28413749
TI - Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective
Matrix Metalloproteinase Inhibitor.
AB - The incorporation of fluorine atoms into functional molecules is of wide interest
in synthetic organic chemistry as well as cognate disciplines. In particular, in
medicinal chemistry, there is a strong desire to positively influence the
physicochemical molecular properties of drug compounds by introducing fluorine
into biologically active molecules. Here, we present targeted fluoro positioning
as the key design principle of converting a weak matrix metalloproteinase-13 (MMP
13) inhibitor into a very potent (IC50=6 nm) and highly selective (selectivity
factors of >1000 over MMP-1, 2, 3, 7, 8, 9, 10, 12, 14) inhibitor with excellent
plasma and microsomal stability, and no binding to the hERG channel (hERG: human
ether-a-go-go related gene).
PMID- 28413748
TI - Thiamine Assays-Advances, Challenges, and Caveats.
AB - Thiamine (vitamin B1) is essential to the health of all living organisms and
deficiency has long been associated with diseases in animals such as fish, birds,
alligators, and domesticated ruminant mammals. Thiamine is also implicated in
several human diseases including Alzheimer's, diabetes, dementia, depression and,
most notably, Wernicke-Korsakoff syndrome and Beriberi disease. Yet, highly
sensitive and specific detection of thiamine remains an analytical challenge, as
pM to nm levels of thiamine need to be detected in environmental and human
samples, respectively, various phosphorylated variants need to be discriminated,
and rapid on-site detection would be highly desirable. Furthermore, appropriate
sample preparation is mandatory, owing to the complexity of the relevant sample
matrices including fish tissues, ocean water, and body fluids. This Review has
two objectives. First, it provides a thorough overview of analytical techniques
published for thiamine detection over the last 15 years. Second, it describes the
principles of analytical approaches that are based on biorecognition and may open
up new avenues for rapid and high-throughput thiamine analysis. Most notably,
periplasmic binding proteins, ribozymes, and aptamers are of particular interest,
as they function as bioaffinity recognition elements that can fill an important
assay technology gap, owing to the unavailability of thiamine-specific commercial
antibodies. Finally, the authors provide brief evaluations of key outcomes of the
major assay concepts and suggest how innovative techniques could help develop
sensitive and specific thiamine analytical test systems.
PMID- 28413750
TI - An Optically Isotropic Antiferroelectric Liquid Crystal (OI-AFLC) Display Mode
Operating over a Wide Temperature Range using Ternary Bent-Core Liquid Crystal
Mixtures.
AB - We report on the synthesis and characterization of bent-core liquid crystal (LC)
compounds and the preparation of mixtures that provide an optically isotropic
antiferroelectric (OI-AFLC) liquid crystal display mode over a very wide
temperature interval and well below room temperature. From the collection of
compounds synthesized during this study, we recognized that several ternary
mixtures displayed a modulated SmCaPA phase down to below -40 degrees C and up
to about 100 degrees C on both heating and cooling, as well as optical tilt
angles in the transformed state of approximately 45 degrees (optically isotropic
state). The materials were fully characterized and their liquid crystal as well
as electro-optical properties analyzed by polarized optical microscopy,
differential scanning calorimetry, synchrotron X-ray diffraction, dielectric
spectroscopy, and electro-optical tests.
PMID- 28413751
TI - Step-by-Step Design and Synthesis of Au@SiO2@Phenyl-azathiacrown for SERS-Based
Specific Quantification of Inorganic Mercury.
AB - Direct SERS-based quantification of inorganic metal species has been a problem,
because they have a small Raman cross-section or even no vibrational mode. Here,
we report a new strategy for SERS-based quantification of such metal species, as
exemplified by inorganic mercury (HgII) in waters. Step-by-step design and
synthesis from azathioethers [3, 9-dithia-6-monoazaundecane (DMA) and 3,6,12,15
tetrathia-9-monoazaheptadecane (TTM)] to an azathiacrown [7-aza-1,4,10,13
tetrathiacyclohexadecane (NS4)] demonstrate an improved S-pulling effect and size
fit specificity towards HgII to form Hg-S bonds. Modification of NS4 on the
surface of Au@SiO2 by using a 4-(bromomethyl)benzoic linker enabled direct SERS
based specific quantification of HgII for the first time, in which the ultrathin
layer (ca. 2 nm) that covered the Au core (55 nm) could be a barrier preventing
the Au core from having direct interaction with the HgII, and with phenyl serving
as an internal standard (IS). The ratio of the Hg-S SERS band intensity at 270 cm
1 to that of IS [(gammaCC+gammaCCC) at 1046 cm-1] was practically proportional to
the concentration of HgII, eliminating the inevitable uncertainties encountered
in SERS-based measurements. Such a methodology is expected to pave a new way for
SERS-based quantification of inorganic metal species when specific complexing
substrates and suitable ISs are designed.
PMID- 28413752
TI - Tetrahydropyranyl: A Non-aromatic, Mild-Acid-Labile Group for Hydroxyl Protection
in Solid-Phase Peptide Synthesis.
AB - The use of the tetrahydropyranyl (Thp) group for the protection of serine and
threonine side-chain hydroxyl groups in solid-phase peptide synthesis has not
been widely investigated. Ser/Thr side-chain hydroxyl protection with this acid
labile and non-aromatic moiety is presented here. Although Thp reacts with free
carboxylic acids, it can be concluded that to introduce Thp ethers at the
hydroxyl groups of N-protected Ser and Thr, protection of the C-terminal carboxyl
group is unnecessary due to the lability of Thp esters. Thp-protected Ser/Thr
containing tripeptides are synthesized and the removal of Thp studied in low
concentrations of trifluoroacetic acid in the presence of cation scavengers.
Given its general stability to most non-acidic reagents, improved solubility of
its conjugates and ease with which it can be removed, Thp emerges as an effective
protecting group for the hydroxyl groups of Ser and Thr in solid-phase peptide
synthesis.
PMID- 28413754
TI - An Approach Toward Replacing Vanadium: A Single Organic Molecule for the Anode
and Cathode of an Aqueous Redox-Flow Battery.
AB - By combining a viologen unit and a 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)
radical in one single combi-molecule, an artificial bipolar redox-active
material, 1-(4-(((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)carbonyl)benzyl)
1'-methyl-[4,4'-bipyridine]-1,1'-diium-chloride (VIOTEMP), was created that can
serve as both the anode (-0.49 V) and cathode (0.67 V vs. Ag/AgCl) in a water
based redox-flow battery. While it mimics the redox states of flow battery metals
like vanadium, the novel aqueous electrolyte does not require strongly acidic
media and is best operated at pH 4. The electrochemical properties of VIOTEMP
were investigated by using cyclic voltammetry, rotating disc electrode
experiments, and spectroelectrochemical methods. A redox-flow battery was built
and the suitability of the material for both electrodes was demonstrated through
a polarity-inversion experiment. Thus, an organic aqueous electrolyte system
being safe in case of cross contamination is presented.
PMID- 28413753
TI - Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a
Polysilane/SiO2-Supported Palladium Catalyst under Continuous-Flow Conditions.
AB - Hydrogenation of nitriles to primary amines with heterogeneous catalysts under
liquid-phase continuous-flow conditions is described. Newly developed
polysilane/SiO2-supported Pd was found to be an effective catalyst and various
nitriles were converted into primary amine salts in almost quantitative yields
under mild reaction conditions. Interestingly, a complex mixture was obtained
under batch conditions. Lifetime experiments showed that this catalyst remained
active for more than 300 h (TON>=10 000) without loss of selectivity and no metal
leaching from the catalyst occurred. By using this continuous-flow hydrogenation,
synthesis of venlafaxine, an antidepressant drug, has been accomplished.
PMID- 28413755
TI - One-Pot Synthesis of a bis-Pocket Corrole through a 14-fold Bromination Reaction.
AB - A one-pot protocol, effecting 14-fold bromination with elemental bromine, has
afforded copper beta-octabromo-meso-tris(2,6-dibromo-3,5-dimethoxyphenyl)corrole,
a new bis-pocket metallocorrole. The Cu complex underwent smooth demetalation
under reductive conditions, affording the free corrole ligand, which in turn
could be readily complexed to MnIII and AuIII. A single-crystal X-ray structure
was obtained for the MnIII complex.
PMID- 28413756
TI - Trifluoroethoxy-Coated Subphthalocyanine affects Trifluoromethylation of Alkenes
and Alkynes even under Low-Energy Red-Light Irradiation.
AB - Photoredox chemical reactions induced by visible light have undergone a
renaissance in recent years. Polypyridyl dyes such as Ir(ppy)3 and Ru(bpy)3 are
key catalysts in this event, and blue- or white-light irradiation is required for
the chemical transformations. However, it remains a challenge to achieve
reactions under the lower energy of red light. We disclose, herein, that
trifluoroethoxy-coated subphthalocyanine realizes the red-light-driven
trifluoromethylation of alkenes and alkynes with trifluoromethyl iodide in good
to-high yields. Perfluoroalkylations were also achieved under red light. The
reaction mechanism is discussed with the support of UV/Vis spectroscopy and
cyclic voltammetry of trifluoroethoxy-coated subphthalocyanine. Light
irradiation/dark study also supports the proposed mechanism.
PMID- 28413758
TI - De Novo Modular Development of a Foldameric Protein-Protein Interaction Inhibitor
for Separate Hot Spots: A Dynamic Covalent Assembly Approach.
AB - Protein-protein interactions stabilized by multiple separate hot spots are highly
challenging targets for synthetic scaffolds. Surface-mimetic foldamers bearing
multiple recognition segments are promising candidate inhibitors. In this work, a
modular bottom-up approach is implemented by identifying short foldameric
recognition segments that interact with the independent hot spots, and connecting
them through dynamic covalent library (DCL) optimization. The independent hot
spots of a model target (calmodulin) are mapped with hexameric beta-peptide
helices using a pull-down assay. Recognition segment hits are subjected to a
target-templated DCL ligation through thiol-disulfide exchange. The most potent
derivative displays low nanomolar affinity towards calmodulin and effectively
inhibits the calmodulin-TRPV1 interaction. The DCL assembly of the folded
segments offers an efficient approach towards the de novo development of a high
affinity inhibitor of protein-protein interactions.
PMID- 28413759
TI - Acid-Responsive N-Heteroacene-Based Material Showing Multi-Emission Colors.
AB - An acid-responsive N-heteroacene-based material has been prepared, which shows a
blue emission color in a film. The protonation of this material in a thin film
gives rise to remarkable changes in luminescent color compared to that in
solution states. As the protonation of N-heteroacene molecules in films gradually
occurs, their emission color can be tuned by adjusting the exposure time of the
thin films to HCl vapor.
PMID- 28413757
TI - Versatile Two-Step Functionalization of Nanocarbons: Grafting of Propargylic
Groups and Click Post-Functionalization.
AB - Chemical functionalization of nanocarbons is essential for further applications
in various fields. We developed a facile, inexpensive, and gram-scale one-pot
route towards alkynyl-functionalized nanocarbons. Nucleophilic
addition/propargylic capture places alkyne moieties at the surface of carbon
nanotubes (CNTs) and graphene. Thermogravimetric analysis coupled with mass
spectrometry and Raman analysis confirmed the efficiency of this process.
Conductivity measurements demonstrated the maintenance of the CNT electrical
properties. The attached alkynyl moieties were reacted with various azide
derivatives through the click-Huisgen [3+2] cycloaddition and characterized with
XPS. The efficient addition of those derivatives enables the application of our
finding in various fields. This route is a reliable and convenient alternative to
the known diazonium functionalization and oxidation-esterification reactions to
graft alkyne groups.
PMID- 28413760
TI - Synthesis of C2-Symmetric Diphosphormonoamidites and Their Use as Ligands in Rh
Catalyzed Hydroformylation: Relationships between Activity and Hydrolysis
Stability.
AB - A series of diphosphoramidites has been synthetized with a piperazine,
homopiperazine, and an acyclic 1,2-diamine unit in the backbone. New compounds
were tested alongside related N-acyl phosphoramidites as ligands in the Rh
catalyzed hydroformylation of n-octenes to investigate their influence on the
activity and regioselectivity. A subsequent study of their hydrolysis stability
revealed that the most stable ligands induced the highest activity in the
catalytic reaction.
PMID- 28413761
TI - Synthesis, Characterization, and Antimicrobial Activity of Near-IR Photoactive
Functionalized Gold Multibranched Nanoparticles.
AB - Surface-modified gold multibranched nanoparticles (AuMs) were prepared by simple
chemical reduction of gold chloride aqueous solution followed by in situ
modification by using water-soluble arenediazonium tosylates with different
functional organic groups. Chemical and morphological structures of the prepared
nanoparticles were examined by using transmission electron and scanning electron
microscopies. The covalent grafting of organic compounds was confirmed by
scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX)
and Raman spectroscopy techniques. Covalent functionalization of nanoparticles
significantly expands the range of their potential uses under physiological
conditions, compared with traditional non-covalent or thiol-based approaches. The
antibacterial effect of the surface-modified AuMs was evaluated by using
Escherichia coli and Staphylococcus epidermidis bacteria under IR light
illumination and without external triggering. Strong plasmon resonance on the
AuMs cups leads to significant reduction of the light power needed kill bacteria
under the mild conditions of continuous illumination. The effect of the surface
modified AuMs on the light-induced antibacterial activities was founded to be
dependent on the grafted organic functional groups.
PMID- 28413762
TI - Photothermal Conversion of W18O49 with a Tunable Oxidation State.
AB - W18O49 with a tunable oxidation state was prepared by addition of NaNO3 or NaBH4
as a redox agent in the solvothermal system. The addition of redox agents has no
influence on the crystallization of W18O49. The obtained W18O49 structures keep
their morphology as a bundle of nanowires with a regular hexagonal on the cross
section. W18O49 exhibits strong valence-dependent absorption features in the near
IR region. Reduced W18O49 with more W5+ has a higher concentration of oxygen
vacancies, which enhances the localized surface plasmon resonance effect. Reduced
W18O49 exhibits a high photothermal conversion efficiency of 59.6 % and has good
photothermal stability.
PMID- 28413763
TI - Relationship between Side-Chain Polarity and the Self-Assembly Characteristics of
Perylene Diimide Derivatives in Aqueous Solution.
AB - Perylene-3,4,9,10-tetracarboxylic acid diimides (PDIs) have recently gained
considerable interest for water-based biosensing applications. PDIs have been
studied intensively in the bulk state, but their physical properties in aqueous
solution in interplay with side-chain polarity are, however, poorly understood.
Therefore, three perylene diimide based derivatives were synthesized to study the
relationship between side-chain polarity and their self-assembly characteristics
in water. The polarity of the side chains was found to dictate the size and
morphology of the formed aggregates. Side-chain polarity rendered the self
assembly and photophysical properties of the PDIs-both important for imminent
water-based applications-and these were revealed to be especially responsive to
changes in solvent composition.
PMID- 28413764
TI - Engineering Functions into Platinum and Platinum-Rhodium Nanoparticles in a One
Step Microwave Irradiation Synthesis.
AB - Platinum (Pt) and platinum-rhodium (PtRh) nanoparticles (NPs) are active
catalysts for a range of important industrial reactions, and their response has
been shown to be affected by size, morphology, composition, and architectural
configuration. We report herein the engineering of these functionalities into NPs
by suitably modifying our single-step fabrication process by using microwave
irradiation dielectric heating. NPs with different morphologies are acquired by
manipulating the reaction kinetics with the concentration of the capping agent
while keeping the reaction time constant. Pt@Rh core@shell octopod-cube, Pt
truncated-cube, and cube and small-sphere NPs having "near-monodisperse"
distributions and average sizes in the range of 4 to 18 nm are obtained. By
increasing the microwave time the composition of Pt@Rh can be tuned, and NPs with
a Rh-rich shell and a tunable Pt100-x Rh x (x<=41 at %) core are fabricated.
Finally, alloy bimetallic PtRh NPs with controlled composition are designed by
simultaneous tuning of the relative molar ratio of the metal precursors and the
microwave irradiation time.
PMID- 28413765
TI - Experimental and Theoretical Examination of the Radical Cations Obtained from the
Chemical and Electrochemical Oxidation of 5-Aminothiazoles.
AB - Chemical or electrochemical one-electron oxidation of 5-N-arylaminothiazoles was
found to afford stable radical cations. For chemical oxidation, 1 equivalent of
[(4-BrC6H4)3N][SbCl6] (Magic Blue, MB) was added to CH2Cl2 solutions of the
thiazoles, and the thus-obtained radicals showed light absorption in the near
infrared region. Electrochemical oxidation also led to bathochromic shifts in the
absorption bands, and the obtained spectra were similar to those derived from the
chemically oxidized species. These radicals afforded electron paramagnetic
resonance (EPR) spectra that are consistent with the notion of stable nitrogen
radicals (half-life<=385 h). The EPR spectrum of a thiazole containing 4
dimethylaminophenyl groups on the nitrogen atom at the 5-position changed
significantly upon adding >3 equivalents of MB. Details of the electronic
structures of the experimentally obtained radical cations were generated from
theoretical calculations.
PMID- 28413766
TI - Five-Component Self-Assembly of Cucurbituril-Based Hetero-pseudorotaxanes.
AB - [5]Pseudorotaxanes can be obtained by self-sorting using heteroditopic guests and
various cucurbituril homologues as hosts. The assembly and chemically induced
disassembly of the pseudorotaxanes can be monitored by measuring the fluorescence
of the anthracene guest in solution. Mass spectral evidence for the
supramolecular assemblies is obtained in the gas phase. The disassembly in the
gas phase can be achieved by collision-induced dissociation leading to the
corresponding [2]- and [3]pseudorotaxanes.
PMID- 28413767
TI - Unique Image Characteristics of an Occipital Primary Chondroblastic Osteosarcoma:
A Rare Case Report and a Brief Literature Review.
AB - Primary osteosarcomas of the skull and skull base are rare and comprise < 2% of
all skull tumors. In head and neck osteosarcomas, the chondroblastic subtype
occurs most frequently, which has an exceedingly poor outcome, but its image
characteristic remains unknown. Herein, we report a case in the right occipital
bone of the skull base and the unique characteristics of image. Pathologic
examination of the surgical specimens led to the diagnosis of chondroblastic
osteosarcomas. We believe those image characteristics can improve the
understanding of skull chondroblastic osteosarcoma and the preoperative
diagnosis.
PMID- 28413768
TI - Surgical Resection of an Optic Nerve Sheath Meningioma: Relevance of Endoscopic
Endonasal Approaches to the Optic Canal.
AB - Optic nerve sheath meningiomas (ONSMs) account for less than 2% of meningiomas
and 1.7% of orbital tumors. Although rare, the management of these tumors is
important as unilateral blindness often results in untreated cases. Radiotherapy
has emerged as the preferred treatment. However, therapies for ONSMs are
controversial due to the variable natural history of the disease and limitations
of surgical and radiotherapy options. A 60-year-old woman presented with
monocular left diminished color perception and blurred vision. Magnetic resonance
imaging demonstrated a homogenously enhancing 5-mm left optic nerve mass with
evidence of nerve compression. Conservative management was advised. However, 1
month after diagnosis her visual acuity deteriorated further. Because of the
small focal location of the tumor within the optic canal, surgery was considered.
Given the tumor's location inferomedial to the optic nerve, an endoscopic
endonasal approach to the optic canal was performed. This patient recovered fully
with resolution of visual symptoms immediately following surgery. Postoperative
imaging 24 hours after surgery demonstrated gross total resection of the tumor; 1
year postoperatively the patient has a normal ophthalmologic examination. This
report highlights the value of endoscopic endonasal approaches in the management
of select optic canal pathology, otherwise inaccessible via transcranial
approaches.
PMID- 28413769
TI - Update on Biomarkers to Monitor Clinical Efficacy Response During and Post
Treatment in Allergen Immunotherapy.
AB - Allergen immunotherapy (AIT) is an immune modulating treatment for allergic
diseases. Although highly effective, some patients do not respond to the
treatment. To date there are no surrogate biomarkers that are predictive of the
clinical response to AIT. More and more is known about the underlying
immunological mechanism involved in AIT. Through modulation of both innate and
adaptive immune responses, involving reduced ILC2 and enhanced Treg and Breg
induction and functionality, along with induction of IgG4 antibody production
which have the capacity to inhibit both allergen-induced basophil responsiveness
and CD23-mediated IgE-facilitated allergen presentation, the result is an immune
skewing towards a more balanced Type I response. So far, however there is not a
clear correlation with the observed immunological changes and predictive
correlates of clinical efficacy. The most promising biomarker of successful AIT
is IgE-FAB as a reflection of functional IgG4. Cellular responses and cytokine
analysis gives a great deal of insight into the mechanisms of AIT but may not
represent useful or indeed reliable biomarkers in a clinical setting. There is a
need for more research for confirmation and interpretation of the possible
association with biomarkers and clinical response to AIT.
PMID- 28413770
TI - Biophysical regulation of cell reprogramming.
AB - Induced pluripotent stem (iPS) cell reprogramming and direct reprogramming are
promising approaches for disease modeling and personalized medicine. However,
these processes are yet to be optimized. Biomaterials are increasingly integrated
into cell reprogramming strategies in order to engineer the microenvironment,
improve reprogramming efficiency and achieve effective in situ cell
reprogramming. Although there are some studies on the role of biomaterials in iPS
cell reprogramming, their effect on direct cell conversion has not been fully
explored. Here we review the recent advances in the use of biomaterials for iPS
cell reprogramming and direct reprogramming, with a focus on the biophysical
aspect. We further highlight the future challenges and directions of the field.
PMID- 28413772
TI - Postoperative complications with cryotherapy in bone tumors.
AB - The technique of cryosurgery has been used to control local recurrence in a
variety of benign and malignant bone tumors. Early studies revealed significant
complication rates (25%) that included fracture, infection, and soft tissue
injury. Our method of cryosurgery has yielded excellent tumor control with
improved complication rates. The objective of this study is to determine the
characteristics of postoperative complications after pouring liquid nitrogen into
curettaged bone defects, and to review our current indications and surgical
technique in bone tumor management. We reviewed charts in over 200 patients who
received cryoablation for bone tumors from 1994 to 2015. Imaging studies were
evaluated in all patients diagnosed with a complication. All patients receiving
cryotherapy had soft tissue management intraoperatively that included warm saline
directed to the structures. Liquid nitrogen was poured into the bone defect and
in some cases, additional spraying with a cryogun into the defect was performed.
The majority of cryotherapy was used in cases of active or aggressive benign
tumors. Our low complication rate of 2.34% included 1 post-operative fracture, 3
infection, and 1 paraesthesia. Bone graft or cementation was used in the majority
of patients, all of which fully incorporated. Cryoablation is an excellent from
of adjuvant therapy for active and aggressive benign tumors and may be used in
malignant tumors as well. Soft tissue protection is critical to avoid skin
necrosis and wound breakdown. We recommend the use of cryotherapy in active and
aggressive bone tumors as an adjuvant treatment prior to bone grafting or
cementation.
PMID- 28413773
TI - A M. avium complex spondylodiscitis in a middle-aged woman with diabetes.
AB - Spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral
disk space, is the reason for low back pain in a minority of cases. This is
caused by various pathogens. Mycobacterium tuberculosis is responsible for 17-39%
of all the cases of spondylodiscitis. On the contrast, spondylodiscitis from non
tuberculous mycobacteria is extremely rare in literature. We describe a 68 -year
old diabetic woman which is the first case of bone marrow involvement by M.
intracellulare (member of M avium complex)with spondylodiscitis.
PMID- 28413771
TI - Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal
women with hormone sensitive breast cancer: Joint position statement of the IOF,
CABS, ECTS, IEG, ESCEO IMS, and SIOG.
AB - BACKGROUND: Several guidelines have been reported for bone-directed treatment in
women with early breast cancer (EBC) for averting fractures, particularly during
aromatase inhibitor (AI) therapy. Recently, a number of studies on additional
fracture related risk factors, new treatment options as well as real world
studies demonstrating a much higher fracture rate than suggested by randomized
clinical controlled trials (RCTs). Therefore, this updated algorithm was
developed to better assess fracture risk and direct treatment as a position
statement of several interdisciplinary cancer and bone societies involved in the
management of AI-associated bone loss (AIBL). PATIENTS AND METHODS: A systematic
literature review identified recent advances in the management of AIBL. Results
with individual agents were assessed based on trial design, size, follow-up, and
safety. RESULTS: Several fracture related risk factors in patients with EBC were
identified. Although, the FRAX algorithm includes fracture risk factors (RF) in
addition to BMD, it does not seem to adequately address the effects of AIBL.
Several antiresorptive agents can prevent and treat AIBL. However, concerns
regarding compliance and long-term safety remain. Overall, the evidence for
fracture prevention is strongest for denosumab 60 mg s.c. every 6 months.
Additionally, recent studies as well as an individual patient data meta-analysis
of all available randomized trial data support additional anticancer benefits
from adjuvant bisphosphonate treatment in postmenopausal women with a 34%
relative risk reduction in bone metastasis and 17% relative risk decrease in
breast cancer mortality that needs to be taken into account when advising on
management of AIBL. CONCLUSIONS: In all patients initiating AI treatment,
fracture risk should be assessed and recommendation with regard to exercise and
calcium/vitamin D supplementation given. Bone-directed therapy should be given to
all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one
additional RF, or with >=2 risk factors (without BMD) for the duration of AI
treatment. Patients with T-score>-1.5 SD and no risk factors should be managed
based on BMD loss during the first year and the local guidelines for
postmenopausal osteoporosis. Compliance should be regularly assessed as well as
BMD on treatment after 12 - 24 months. Furthermore, because of the decreased
incidence of bone recurrence and breast cancer specific mortality, adjuvant
bisphosphonates are recommended for all postmenopausal women at significant risk
of disease recurrence.
PMID- 28413774
TI - A diffuse lung emphysema, severe pulmonary hypertension and lack of airflow
limitation.
AB - Pulmonary veno-occlusive disease is characterized by remodeling of pulmonary
arteries, capillaries and venules. We report a case of diffuse lung emphysema and
pulmonary veno-occlusive disease with the characteristic of having no airflow
limitation. A very low diffusing capacity for carbon monoxide and results of high
resolution computed tomography of the chest suggested pulmonary veno-occlusive
disease. The diagnosis was confirmed on histological analysis after lung
transplantation. The combination of results of the computed tomography of the
chest and the histological analysis suggested a relationship between diffuse lung
emphysema and remodeling of pulmonary vessels. A distinctive pattern of mild-to
moderate airflow limitation in patients with chronic obstructive pulmonary
disease and severe pulmonary hypertension has been described. This observation of
the combination of diffuse emphysema, pulmonary veno-occlusive disease and no
airflow limitation supports further pathophysiological studies on severe
pulmonary hypertension in chronic obstructive pulmonary disease.
PMID- 28413775
TI - An interesting case of mycoplasma pneumonia associated multisystem involvement
and diffuse alveolar hemorrhage.
AB - Severe mycoplasma pneumonia is a rare entity with only 0.5-2% of cases having a
fulminant course. We present a 74-year-old woman with hypertension, diabetes
mellitus and remote history of marginal zone B-cell lymphoma admitted with
abdominal pain and diarrhea of 1-2 days associated with body-aches, dyspnea, dry
cough and weight loss for 2-3 weeks. On physical exam, she was febrile,
tachypneic, tachycardic and hypoxic on room air. Chest examination revealed
diffuse crackles and end-expiratory wheezes. Laboratory tests showed anemia,
acute-on-chronic kidney injury and hyaline casts and epithelial cells in the
urine analysis. Chest roentgenogram and computed tomograhphy scan showed
pulmonary infiltrates. Intravenous ceftriaxone and azithromycin with
bronchodilators were initiated. Her clinical course was complicated by hypoxic
respiratory failure, hemoptysis, and worsening of infiltrates, requiring
intubation and mechanical ventilation. Bronchoscopic bronchoalveolar lavage was
consistent with diffuse alveolar hemorrhage (DAH). The patient's serum was
positive for IgM antibody to Mycoplasma pneumoniae [1134 U/mL] and Anti-I
specific IgM-cold-agglutining [1:40]. A diagnosis of severe mycoplasma infection
with DAH was made. The patient was treated with an additional course of
doxycycline, pulse dose steroids and plasmapharesis with good clinical response.
Surgical lung biopsy showed focal acute lung injury. Bone marrow biopsy and fat
pad biopsy were normal. She was liberated from mechanical ventilation and
discharged. She returned within 24 hours of discharge with cardiac arrest and new
onset right-bundle-branch-block. We hypothesize our patient had severe mycoplasma
pneumonia with DAH and multisystem complications of the same including a possible
venous thrombo-embolic episode leading to her demise.
PMID- 28413776
TI - Dissociable neural processes during risky decision-making in individuals with
Internet-gaming disorder.
AB - Risk-taking is purported to be central to addictive behaviors. However, for
Internet gaming disorder (IGD), a condition conceptualized as a behavioral
addiction, the neural processes underlying impaired decision-making (risk
evaluation and outcome processing) related to gains and losses have not been
systematically investigated. Forty-one males with IGD and 27 healthy comparison
(HC) male participants were recruited, and the cups task was used to identify
neural processes associated with gain- and loss-related risk- and outcome
processing in IGD. During risk evaluation, the IGD group, compared to the HC
participants, showed weaker modulation for experienced risk within the bilateral
dorsolateral prefrontal cortex (DLPFC) (t = - 4.07; t = - 3.94; PFWE < 0.05) and
inferior parietal lobule (IPL) (t = - 4.08; t = - 4.08; PFWE < 0.05) for
potential losses. The modulation of the left DLPFC and bilateral IPL activation
were negatively related to addiction severity within the IGD group (r = - 0.55; r
= - 0.61; r = - 0.51; PFWE < 0.05). During outcome processing, the IGD group
presented greater responses for the experienced reward within the ventral
striatum, ventromedial prefrontal cortex, and orbitofrontal cortex (OFC) (t =
5.04, PFWE < 0.05) for potential gains, as compared to HC participants. Within
the IGD group, the increased reward-related activity in the right OFC was
positively associated with severity of IGD (r = 0.51, PFWE < 0.05). These
results provide a neurobiological foundation for decision-making deficits in
individuals with IGD and suggest an imbalance between hypersensitivity for reward
and weaker risk experience and self-control for loss. The findings suggest a
biological mechanism for why individuals with IGD may persist in game-seeking
behavior despite negative consequences, and treatment development strategies may
focus on targeting these neural pathways in this population.
PMID- 28413779
TI - Pufferfish nests vs. parasite hooks: A bizarre resemblance.
AB - Image 1.
PMID- 28413780
TI - Generalized epilepsy in Baraitser-Winter cerebrofrontofacial syndrome.
AB - *Baraitser-Winter cerebrofrontofacial syndrome (BWMS) is caused by actin gene
mutations.*Key features of BWMS are ptosis, hypertelorism, iris colobomata, and
mental retardation.*Generalized epilepsy is seen in half of those with
BWMS.*Seizures in BWMS can be absence, myoclonic, tonic, or tonic-clonic.
PMID- 28413778
TI - Family history and APOE4 risk for Alzheimer's disease impact the neural
correlates of episodic memory by early midlife.
AB - Episodic memory impairment is a consistent, pronounced deficit in pre-clinical
stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for
AD exhibit altered brain function several decades prior to the onset of AD
related symptoms. In the current event-related fMRI study of spatial context
memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a
family history of late onset AD (MA+ FH), or a combined + FH and apolipoprotein E
epsilon4 allele risk factors for AD (MA+ FH + APOE4), will exhibit differences in
encoding and retrieval-related brain activity, compared to - FH - APOE4 MA
controls. We also hypothesized that the two at-risk MA groups will exhibit
distinct patterns of correlation between brain activity and memory performance,
compared to controls. To test these hypotheses we conducted multivariate task,
and behavior, partial least squares analysis of fMRI data obtained during
successful context encoding and retrieval. Our results indicate that even though
there were no significant group differences in context memory performance, there
were significant differences in brain activity and brain-behavior correlations
involving the hippocampus, inferior parietal cortex, cingulate, and precuneus
cortex in MA with AD risk factors, compared to controls. In addition, we observed
that brain activity and brain-behavior correlations in anterior-medial PFC and in
ventral visual cortex differentiated the two MA risk groups from each other, and
from MAcontrols. Our results indicate that functional differences in episodic
memory-related regions are present by early midlife in adults with + FH and +
APOE-4 risk factors for late onset AD, compared to middle-aged controls.
PMID- 28413781
TI - Sequencing and de novo transcriptome assembly of the Chinese giant salamander
(Andrias davidianus).
AB - Next-generation technologies for determination of genomics and transcriptomics
composition have a wide range of applications. Andrias davidianus, has become an
endangered amphibian species of salamander endemic in China. However, there is a
lack of the molecular information. In this study, we obtained the RNA-Seq data
from a pool of A. davidianus tissue including spleen, liver, muscle, kidney,
skin, testis, gut and heart using Illumina HiSeq 2500 platform. A total of
15,398,997,600 bp were obtained, corresponding to 102,659,984 raw reads. A total
of 102,659,984 reads were filtered after removing low-quality reads and trimming
the adapter sequences. The Trinity program was used to de novo assemble 132,912
unigenes with an average length of 690 bp and N50 of 1263 bp. Unigenes were
annotated through number of databases. These transcriptomic data of A. davidianus
should open the door to molecular evolution studies based on the entire
transcriptome or targeted genes of interest to sequence. The raw data in this
study can be available in NCBI SRA database with accession number of SRP099564.
PMID- 28413777
TI - Sex differences in the interacting roles of impulsivity and positive alcohol
expectancy in problem drinking: A structural brain imaging study.
AB - Alcohol expectancy and impulsivity are implicated in alcohol misuse. However, how
these two risk factors interact to determine problem drinking and whether men and
women differ in these risk processes remain unclear. In 158 social drinkers (86
women) assessed for Alcohol Use Disorder Identification Test (AUDIT), positive
alcohol expectancy, and Barratt impulsivity, we examined sex differences in these
risk processes. Further, with structural brain imaging, we examined the neural
bases underlying the relationship between these risk factors and problem
drinking. The results of general linear modeling showed that alcohol expectancy
best predicted problem drinking in women, whereas in men as well as in the
combined group alcohol expectancy and impulsivity interacted to best predict
problem drinking. Alcohol expectancy was associated with decreased gray matter
volume (GMV) of the right posterior insula in women and the interaction of
alcohol expectancy and impulsivity was associated with decreased GMV of the left
thalamus in women and men combined and in men alone, albeit less significantly.
These risk factors mediated the correlation between GMV and problem drinking.
Conversely, models where GMV resulted from problem drinking were not supported.
These new findings reveal distinct psychological factors that dispose men and
women to problem drinking. Although mediation analyses did not determine a causal
link, GMV reduction in the insula and thalamus may represent neural phenotype of
these risk processes rather than the consequence of alcohol consumption in non
dependent social drinkers. The results add to the alcohol imaging literature
which has largely focused on dependent individuals and help elucidate alterations
in brain structures that may contribute to the transition from social to habitual
drinking.
PMID- 28413782
TI - APMicroDB: A microsatellite database of Acyrthosiphon pisum.
AB - Pea aphids represent a complex genetic system that could be used for QTL
analysis, genetic diversity and population genetics studies. Here, we described
the development of first microsatellite repeat database of the pea aphid
(APMicroDB), accessible at "http://deepaklab.com/aphidmicrodb". We identified
3,40,233 SSRs using MIcroSAtellite (MISA) tool that was distributed in 14,067
(out of 23,924) scaffold of the pea aphid. We observed 89.53% simple repeats of
which 73.41% were mono-nucleotide, followed by di-nucleotide repeats. This
database stored information about the repeats kind, GC content, motif type (mono
hexa), genomic location etc. We have also incorporated the primer information
derived from Primer3 software of the 2504 bp flanking region of the identified
marker. Blast tool is also provided for searching the user query sequence for
identified marker and their primers. This work has an immense use for scientific
community working in the field of agricultural pest management, QTL mapping, and
host-pathogen interaction analysis.
PMID- 28413784
TI - Correction.
AB - [This corrects the article DOI: 10.7860/JCDR/2015/11926.6278.].
PMID- 28413783
TI - Two single nucleotide polymorphisms sites in alpha1-AT gene and their association
with somatic cell score in Chinese Holstein cows.
AB - BACKGROUND: Alpha 1-antitrypsin (alpha1-AT) may affect the susceptibility of
mastitis in dairy cattle for its possible role in the protection of lactoferrin
from proteolytic degradation in the mammary. Milk somatic cell score (SCS) is a
logarithmic transformation of the milk somatic cell count widely used as an index
to evaluate mastitis. To study the relationships of alpha1-AT gene and SCS in
Chinese Holstein cows, methods of PCR-SSCP, DNA sequencing, PCR-RFLP, and CRS-PCR
technologies were used to detect single nucleotide polymorphisms sites in alpha1
AT gene. RESULTS: Two polymorphic sites at G5503A and G5746C of alpha1-AT gene
were found. AA (0.3633), AB (0.4644) and BB (0.1723) genotypes were detected at
G5503A site, CC (0.3483), CD (0.4906) and DD (0.1611) genotypes were found at
G5746C in Chinese Holstein cows. Least squares mean of SCS for individuals with
BB genotype was significantly lower than that with AA and AB genotype (p < 0.01),
and that with AB genotype was significantly lower than that with AA (p < 0.05).
There was no significant difference among individuals with CC, CD and DD
genotypes (p > 0.05). Least squares mean of SCS for individuals with BBDD
genotype combination were significantly lower than those with AACC and AACD (p <
0.05). CONCLUSIONS: Statistical analysis indicated that B allele and BBDD
genotype combination of alpha1-AT can improve mastitis resistance in dairy
cattle.
PMID- 28413785
TI - Efficacy of erlotinib as first-line maintenance therapy in patients with locally
advanced or metastatic nonsmall cell lung cancer who have not experienced disease
progression or unacceptable toxicity during chemotherapy.
AB - BACKGROUND: First-line maintenance with erlotinib in nonsmall cell lung cancer
(NSCLC) patients without progression after four cycles of chemotherapy was well
tolerated and significantly prolonged progression-free survival (PFS) compared
with placebo. AIM AND DESIGN: This open-label, single arm, Phase IV,
interventional study was designed to evaluate erlotinib as first-line maintenance
after chemotherapy in Indian NSCLC patients. Primary efficacy objective was to
evaluate PFS rate (PFSR) at week 52 and secondary objectives were determination
of PFS, overall survival (OS), overall response rate (ORR), disease control rate,
and safety. SUBJECTS AND METHODS: Patients were treated with erlotinib until
disease progression/death/unacceptable toxicity or end of study. Patients with
disease progression underwent scheduled clinical assessments every 12 weeks
thereafter. Kaplan-Meier estimates were used to evaluate PFSR, PFS, and OS. The
ORR was summarized using number and percentage along with two-sided 95% Clopper
Pearson confidence interval. The incidence of adverse events (AEs) and serious
AEs (SAEs) was tabulated according to severity, outcome, and relationship to
erlotinib. RESULTS: Of the 51 enrolled patients, 47 patients completed the study
(2: Continuing treatment, 41: Disease progression, and 4: Death) and four
patients discontinued treatment (3: Lost to follow-up; 1: Withdrew consent). PFSR
was 22.5% at 12 months, median PFS 99 days (14.14 weeks), and median OS was 671
days (22 months). The probability of OS was 74.5% at 14 months. The ORR was
25.5%, and disease control rate was 55.3%. AEs were reported in 62.7% and SAE in
7.8% of patients. Common AEs were diarrhea and rash. CONCLUSIONS: Erlotinib was
well tolerated by Indian patients in first-line maintenance setting and resulted
in median PFS of 14 weeks and median OS of 22 months better than previously
reported and with no new safety concerns in this population.
PMID- 28413786
TI - Surgical management of bronchopulmonary carcinoids: A single center experience.
AB - INTRODUCTION: Bronchopulmonary carcinoids are uncommon tumors with relatively
indolent biological behavior but a distinct malignant potential. Surgery is the
mainstay of treatment. Our aim was to study preoperative characteristics,
surgical approaches, and outcome in patients with bronchopulmonary carcinoid
tumors. PATIENTS AND METHODS: This retrospective study was done in the Department
of Surgical Oncology of a Tertiary Teaching Hospital of North India. The case
records of all the patients who underwent surgical treatment for lung neoplasms
and were diagnosed to have bronchopulmonary carcinoids were reviewed. Details
concerning the clinical presentation, preoperative therapy, operative procedure,
postoperative complications, and outcome were retrieved from the case records.
RESULTS: Sixteen patients who underwent surgical treatment were found to have
bronchopulmonary carcinoids on histopathological examination. The median age of
the patients was 34 years (range 18-62 years). There were 11 men and five women.
All patients were symptomatic, and the median duration of symptoms was 12 months
(range 6-72 months) before presentation. Six patients had received antitubercular
treatment before presentation, and one patient had been treated with chemotherapy
due to misdiagnosis. Surgical procedures included six pneumonectomies (one with
carinoplasty), four bilobectomies, three lobectomies, and three bronchoplastic
procedures (two with lobectomy and one with bilobectomy). There was no
postoperative mortality; three patients had morbidity in the form of lobar
collapse, prolonged pleural collection, and surgical site infection. With a
median follow-up time of 11 months (range 2-85 months), all the 16 patients are
alive and disease-free. CONCLUSIONS: Delayed presentation and misdiagnosis of
bronchial carcinoid are major concerns in North India. Adequate surgical
resection can be performed without undue morbidity and is associated with good
long-term results.
PMID- 28413787
TI - Billiary obstruction in a metastatic tumor of the pancreas from breast cancer.
PMID- 28413788
TI - A tertiary care experience with paclitaxel and cetuximab as palliative
chemotherapy in platinum sensitive and nonsensitive in head and neck cancers.
AB - BACKGROUND: The combination of paclitaxel and cetuximab (PaCe) has led to an
encouraging response rate in Phase 2 setting with limited toxicity. The aim of
our study was to assess the efficacy of this regimen in our setting in platinum
sensitive and nonsensitive patients. METHODS: This was a retrospective analysis
of head and neck cancer patients treated with weekly PaCe as palliative
chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab
along with 80 mg/m2 of weekly paclitaxel was administered till either disease
progression or withdrawal of patient's consent. The toxicity and response were
noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria,
respectively. The response rates between platinum sensitive and nonsensitive
patients were compared by Chi-square test. Overall survival (OS) and progression
free survival (PFS) were estimated by Kaplan-Meier survival method and log-rank
test was used for comparison. Cox proportional hazard model was used for
identification of factors affecting PFS and OS. RESULTS: One Hundred patients
with a median age of 52 years (interquartile range: 46-56 years) were included.
Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%)
were platinum sensitive. In platinum insensitive patients and sensitive patients,
the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the
symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P =
0.044). The median PFS in platinum insensitive and sensitive patients were 150
and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95%
confidence interval [95% CI]: 168.2-343.8 days) and 314 days (95% CI: 227.6-400.4
days), respectively (P = 0.23). Nineteen patients (19%) had grades 3-4 adverse
events during chemotherapy. CONCLUSION: Weekly paclitaxel combined with cetuximab
has promising efficacy and good tolerability in the palliative setting in
advanced head and neck cancer in both platinum sensitive and insensitive
patients.
PMID- 28413789
TI - Role of neoadjuvant chemotherapy in advanced carcinoma of the hypopharynx and
larynx.
AB - BACKGROUND: To assess the response rate and impact of neoadjuvant chemotherapy
(NACT) in advanced carcinoma of the hypopharynx and larynx. MATERIALS AND
METHODS: This is a retrospective case series of 80 patients with locally advanced
laryngopharynx carcinoma who received NACT from April 2010 to October 2011 at our
tertiary care center. The patients received NACT either for achieving
resectability or for organ preservation. RESULTS: Majority of the patients (60%)
had T4 a disease. Grade 3 and 4 neutropenia was seen in 18%, febrile neutropenia
in 4%, mucositis in 4%, diarrhea in 5%, and vomiting in 3% patients.
Resectability could be achieved in 34%, and larynx was preserved in 51% patients
at a mean follow-up of 13 months. CONCLUSIONS: NACT was safe with acceptable
toxicity. Majority of the patients who achieved resectability had oropharyngeal
involvement. NACT followed by concurrent chemoradiotherapy could provide a high
rate of organ preservation.
PMID- 28413790
TI - Long-term survival in a case of metastatic papillary renal cell carcinoma.
PMID- 28413791
TI - Safety and tolerability of Peg-grafeelTM, a pegfilgrastim, for the prophylactic
treatment of chemotherapy-induced neutropenia and febrile neutropenia: A
prospective, observational, postmarketing surveillance study in India.
AB - BACKGROUND: A granulocyte colony-stimulating factor, pegfilgrastim, is
efficacious though expensive for prophylactic treatment of chemotherapy-induced
neutropenia and febrile neutropenia. Biologics available and accessible today,
having acceptable safety-efficacy profiles, require postapproval studies for
better understanding of such drugs in clinical settings. AIM: This postmarketing
surveillance study evaluated the safety of prophylactic Peg-grafeelTM
(pegfilgrastim) in cancer patients with chemotherapy-induced neutropenia.
SETTINGS AND DESIGN: This prospective, noninterventional, single-arm, open-label
study was conducted at 10 study sites in India. METHODS: Patients received
subcutaneous 6 mg Peg-grafeelTM approximately 24 h following chemotherapy as part
of routine patient care. STATISTICAL ANALYSIS: Data were summarized
descriptively. RESULTS: The study included 250 patients (male: female =
36.4%:63.6%; median age, 54 [16-80] years). Most patients had Stage III (33.2%)
or IV (41.6%) cancers and received cyclophosphamide (37.2%) and doxorubicin
(31.6%) as chemotherapy. On an average, 4 Peg-grafeelTM doses were administered
per patient. Treatment-emergent adverse events (AEs) were reported in 115 (46%)
patients, the most common being vomiting (11.6%), pain (11.2%), nausea (8.4%),
and constipation (8.4%). Peg-grafeelTM-related AEs included pain (3.2%), asthenia
(2.4%), and arthralgia (1.2%). Bone pain (0.4%) and extremity pain (1.2%) were
rare. Grade 3/4 neutropenia and febrile neutropenia occurred in 4 (1.6%) and 3
(1.2%) patients, respectively. Serious AEs included vomiting (2.8%) and pyrexia
(2%). No new safety concerns were identified. None of the five deaths was
considered related to Peg-grafeelTM. CONCLUSION: The overall safety profile of
Peg-grafeelTM was consistent with the expected safety profile of pegfilgrastim in
patients with advanced malignancies in a clinical setting.
PMID- 28413792
TI - Epedimiologic, clinical profile and factors affecting the outcome in febrile
neutropenia.
AB - BACKGROUND: Febrile neutropenia (FN) is common in cancer patients particularly
hematologic malignancies due to intensive cytotoxic chemotherapy. It is an
important cause of morbidity, mortality and treatment delays. The risk is greater
in patients with ANC < 500/ mm3 and increases dramatically in those with ANC <
100/ mm3 and duration of neutropenia more than 1 week. AIMS AND OBJECTIVES: The
purpose of this study was to evaluate the incidence, demographic characteristics,
clinical profile, mortality, outcome and factors affecting the outcome in
patients with febrile neutropenia (FN) admitted at our Center between January
2011 and November 2012. MATERIALS AND METHODS: All cases of FN admitted in our
Institute between January 2011 and November 2012 were analyzed. Data was analyzed
using IBM statistic SPSS version 19. RESULTS: A total of 333 episodes of FN were
reviewed. Hematologic malignancies accounted for 299 (89.7%) episodes and 88% of
all the episodes had grade 4 neutropenia. There was a significant association
noted between high serum bilirubin, creatinine and outcome. Isolation of an
organism from blood culture, positive findings on chest X-ray and fungal
infection was associated with higher mortality. Association between transfusion
requirements and outcome was analyzed and it was observed that patients who had
multiple component transfusions vs single component ones were at a significantly
higher risk of death. There were only 7 deaths noted among the patient
population. CONCLUSION: Leukemias are the leading cause of FN at our Institute.
Higher bilirubin, creatinine, chest imaging favoring pneumonia, positive isolates
and multiple transfusions had significant association with mortality. Large scale
prospective studies are needed to determine the association of preemptive therapy
with higher mortality. The outcome of high risk FN in this study is favorable.
PMID- 28413793
TI - Pediatric hematological malignancy: Identification of issues involved in the road
to diagnosis.
AB - INTRODUCTION: Childhood malignancy, although a rare phenomenon, is still the
leading cause of mortality in the pediatric population. Early diagnosis and
treatment are imperative for the achievement of optimal prognosis. The study of
factors facilitating the delay in diagnosis is thus of utmost importance, to both
shorten the diagnostic delay and allow for early therapeutic intervention,
facilitating a higher prognosis. OBJECTIVE: To assess the referral pattern and
the identification of potential delays in the diagnosis of childhood malignancy
in a developing country. METHODOLOGY: The study was conducted in the Pediatric
Hematology and Oncology department of Sri Ramachandra University, Chennai, India.
The study included randomly selected 70 pediatric patients diagnosed with a
hematological malignancy, from July 2012-August 2013. The parents were
interviewed using a prepared questionnaire about patient symptomatology,
interaction with healthcare providers, final diagnosis, and referral details.
Data were statistically analyzed using Statistica(r) (STATsoft). RESULTS: 70
patients were included in the study (69% boys, 31% girls). The diagnostic delay
was primarily due to the delay experienced in the healthcare system, with a mean
delay of 26 days (Median: 18; Range: 5-39). Those from a lower socioeconomic
background and whom opted for a non-allopathic treatment approach experienced
higher diagnostic delays. Diagnostic time was significantly shorter for those who
visited a pediatrician versus the patients who visited a general physician or
super specialties (P = 0.043). CONCLUSIONS: Diagnostic delay is often associated
with an extensive disease presentation, an aggressive therapeutic approach, and
has a negative impact on patient prognosis. To lower mortality rate and
facilitate a favourable prognosis, diagnosis requires a high degree of clinical
suspicion and immediate intervention.
PMID- 28413794
TI - Comparative evaluation of iodine-131 metaiodobenzylguanidine and 18
fluorodeoxyglucose positron emission tomography in assessing neural crest tumors:
Will they play a complementary role?
AB - BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has
established a role in the evaluation of several malignancies. However, its
precise clinical role in the neural crest cell tumors continues to evolve.
PURPOSE: The purpose of this study was to compare iodine-131
metaiodobenzylguanidine (131I-MIBG) and FDG-PET of head to head in patients with
neural crest tumors both qualitatively and semiquantitatively and to determine
their clinical utility in disease status evaluation and further management.
MATERIALS AND METHODS: A total of 32 patients who had undergone 131I-MIBG and FDG
PET prospectively were evaluated and clinicopathologically grouped into three
categories: neuroblastoma, pheochromocytoma, and medullary carcinoma thyroid.
RESULTS: In 18 patients of neuroblastoma, FDG PET and 131I-MIBG showed patient
specific sensitivity of 84% and 72%, respectively. The mean maximum standardized
uptake value (SUVmax) of primary lesions in patients with unfavorable histology
was found to be relatively higher than those with favorable histology (5.18 +/-
2.38 vs. 3.21 +/- 1.69). The mean SUVmaxof two common sites (posterior superior
iliac spine [PSIS] and greater trochanter) was higher in patients with involved
marrow than those with uninvolved one (2.36 and 2.75 vs. 1.26 and 1.34,
respectively). The ratio of SUVmaxof the involved/contralateral normal sites was
2.16 +/- 1.9. In equivocal bone marrow results, the uptake pattern with SUV
estimation can depict metastatic involvement and help in redirecting the biopsy
site. Among seven patients of pheochromocytoma, FDG-PET revealed 100% patient
specific sensitivity. FDG-PET detected more metastatic foci than 131I-MIBG (18
vs. 13 sites). In seven patients of medullary carcinoma thyroid, FDG-PET
localized residual, recurrent, or metastatic disease with much higher sensitivity
(32 metastatic foci with 72% patient specific sensitivity) than 131I-MIBG,
trending along the higher serum calcitonin levels. CONCLUSIONS: FDG-PET is not
only a good complementary modality in the management of neural crest cell tumors
but also it can even be superior, especially in cases of 131I-MIBG nonavid
tumors.
PMID- 28413795
TI - Opisthorchiasis, hypercholesterolemia, and cholangiocarcinoma: A reappraisal.
PMID- 28413796
TI - Duplicate publication and the need to strengthen editorial policy of the journal.
PMID- 28413797
TI - A rare case of brain metastasis in a patient with osteosarcoma.
PMID- 28413798
TI - Treatment planning challenges for prosthesis prostate cancer patients in
radiation therapy.
PMID- 28413799
TI - Lomustine induced acute pulmonary toxicity in a pediatric medulloblastoma
survivor.
PMID- 28413800
TI - Ineffective legislation affecting health of adolescents.
PMID- 28413801
TI - Fatty but starving marrow! Gelatinous transformation of bone marrow secondary to
plasma cell disorder and all-trans-retinoic acid therapy: A report of two cases.
PMID- 28413802
TI - First reported case of alveolar soft part sarcoma in constitutional mismatch
repair deficiency syndrome tumor spectrum - diagnosed in one of the siblings with
constitutional mismatch repair deficiency.
PMID- 28413803
TI - Epidemiology of burn injuries in Nepal: a systemic review.
AB - Burn is a global public health problem associated with significant morbidity and
mortality, mostly in low- and middle-income countries. Southeast-Asian countries
share a big burden of burn injuries, and Nepal is not an exception. We performed
a systemic review to examine the epidemiological characteristics of burn injures
in Nepal. Relevant epidemiological studies were identified through systemic
search in PubMed, EMBASE, and Google Scholar. Reference lists from relevant
review articles were also searched. Studies were included if they meet our
selection criteria. Eight studies were included in our systemic review. Most of
the burn victims belong to the working age group between 15-60 years old. Flame
burns were found to be the most common cause of burn injury followed by scald
burns, whereas scald burns were the most common cause of burn injury among the
pediatric population. Most patients sustained less severe burn injuries, with
home being the most common place of burn injury. The average hospital stay among
the burn victims ranged from 13 to 60 days. Mortality among the burn victims
ranged from 4.5 to 23.5%, with highest mortality among the flame burn patients.
Developed nations have significantly reduced the burn incidence through effective
intervention program. Although, burn injuries are the leading cause of morbidity
and mortality in Nepal, effective intervention programs are lacking due to the
limited epidemiological data related to burn injuries. Further large scale
research is imperative to investigate the problem and assess the effectiveness of
an intervention program.
PMID- 28413804
TI - Corneal compensation of presbyopia: PresbyLASIK: an updated review.
AB - ABSTRACT: The main purpose of this review is to compare and analyze the results
of the main PresbyLASIK approaches; central and peripheral. SUMMARY: A
comprehensive research was conducted in PUBMED using keywords like "presbyopia
correction", "PresbyLASIK", "Corneal multifocality", "Laser blended vision". We
reviewed the PresbyLASIK technique, uncorrected distance visual acuity (UDVA),
corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA),
and corrected near visual acuity (CNVA), and compared the differences between the
techniques.
PMID- 28413805
TI - Release of Airborne Polychlorinated Biphenyls from New Bedford Harbor Results in
Elevated Concentrations in the Surrounding Air.
AB - Qualitatively and quantitatively, we have demonstrated that airborne
polychlorinated biphenyl (PCB) concentrations in the air surrounding New Bedford
Harbor (NBH) are caused by its water PCB emissions. We measured airborne PCBs at
18 homes and businesses near NBH in 2015, with values ranging from 0.4 to 38 ng m
3, with a very strong Aroclor 1242/1016 signal that is most pronounced closest to
the harbor and reproducible over three sampling rounds. Using U.S. Environmental
Protection Agency (U.S. EPA) water PCB data from 2015 and local meteorology, we
predicted gas-phase fluxes of PCBs from 160 to 1200 MUg m-2 day-1. Fluxes were
used as emissions for AERMOD, a widely applied U.S. EPA atmospheric dispersion
model, to predict airborne PCB concentrations. The AERMOD predictions were within
a factor of 2 of the field measurements. PCB emission from NBH (110 kg year-1,
average 2015) is the largest reported source of airborne PCBs from natural waters
in North America, and the source of high ambient air PCB concentrations in
locations close to NBH. It is likely that NBH has been an important source of
airborne PCBs since it was contaminated with Aroclors more than 60 years ago.
PMID- 28413806
TI - Ryanodine and IP3 receptor-mediated calcium signaling play a pivotal role in
neurological infrared laser modulation.
AB - Pulsed infrared (IR) laser energy has been shown to modulate neurological
activity through both stimulation and inhibition of action potentials. While the
mechanism(s) behind this phenomenon is (are) not completely understood, certain
hypotheses suggest that the rise in temperature from IR exposure could activate
temperature- or pressure-sensitive ion channels or create pores in the cellular
outer membrane, allowing an influx of typically plasma-membrane-impermeant ions.
Studies using fluorescent intensity-based calcium ion ([Formula: see text])
sensitive dyes show changes in [Formula: see text] levels after various IR
stimulation parameters, which suggests that [Formula: see text] may originate
from the external solution. However, activation of intracellular signaling
pathways has also been demonstrated, indicating a more complex mechanism of
increasing intracellular [Formula: see text] concentration. We quantified the
[Formula: see text] mobilization in terms of influx from the external solution
and efflux from intracellular organelles using Fura-2 and a high-speed
ratiometric imaging system that rapidly alternates the dye excitation
wavelengths. Using nonexcitable Chinese hamster ovarian ([Formula: see text])
cells and neuroblastoma-glioma (NG108) cells, we demonstrate that intracellular
[Formula: see text] receptors play an important role in the IR-induced [Formula:
see text], with the [Formula: see text] response augmented by ryanodine receptors
in excitable cells.
PMID- 28413808
TI - Vessel tree tracking in angiographic sequences.
AB - We present a method to track vessels in angiography [contrast filled vessels in
two-dimensional (2-D) x-ray fluoroscopy]. Finding correspondence of a vessel tree
from consecutive angiogram frames provides significant value in computer-aided
clinical applications such as fast vessel tree segmentation, three-dimensional (3
D) vessel topology reconstruction from corresponding centerlines, cardiac motion
understanding, etc. However, establishing an accurate vessel tree correspondence
(vessel tree tracking) is a nontrivial problem due to nonlinear periodic cardiac
and breathing motion in 2-D views, foreshortening, false bifurcations due to 3-D
to 2-D projection, occlusion from other anatomies, etc. The vessel tree is
represented by BSpline curves. The control points of the BSpline curves are
landmarks that are the tracking targets. Our method maximizes the appearance
similarity while preserving the vessel structure. A directed acyclic graph (DAG)
is employed to represent the appearance and shape structure of the vessel tree:
nodes from the DAG encode the appearance of the vessel tree landmarks, and the
edges encode the relative locations between landmarks. The vessel tree tracking
problem turns into finding the most similar tree from the DAG in the next frame,
and it is solved using an efficient dynamic programming algorithm. We performed
evaluations on 62 x-ray angiography sequences (above 1000 frames). Experiment
results show our algorithm is robust to these challenges and delivers better
performance, compared to four existing methods.
PMID- 28413807
TI - From brain to blood vessels and back: a noninvasive optical imaging approach.
AB - The seminal work of Grinvald et al. has paved the way for the use of intrinsic
optical signals measured with reflection methods for the analysis of brain
function. Although this work has focused on the absorption signal associated with
deoxygenation, due to its detailed mapping ability and good signal-to-noise
ratio, Grinvald's group has also described other intrinsic signals related to
increased blood flow, scattering effects directly related to neural activation,
and pulsation effects related to arterial function. These intrinsic optical
signals can also be measured using noninvasive diffuse optical topographic and
tomographic imaging (DOT) methods that can be applied to humans. Here we compare
the reflection and DOT methods and the evidence for each type of intrinsic signal
in these two domains, with particular attention to work that has been conducted
in our laboratory. This work reveals the refined two-way relationship that exists
between vascular and neural phenomena in the brain: arterial health is related to
normal brain structure and function, both across individuals and across brain
regions within an individual, and neural function influences blood flow to
specific cortical regions. DOT methods can provide quantitative tools for
investigating these relationships in normal human subjects.
PMID- 28413810
TI - A subtle economy of time: Social media and the transformation of Indonesia's
Islamic preacher economy.
AB - The article is concerned with the latest developments in Indonesia's Islamic
field. Its focus is on the role of social media in exchange relationships between
Islamic preachers and their constituency. The article first discusses economic
exchanges between preachers and their followers, and then it concentrates on
social exchanges and how they are mediated today. Empirically, the article
delivers insight into the concerns of mostly female Indonesian middle-class
Muslims and shows how preachers have to adjust to the needs of their followers
who are regularly online. Theoretically, the article offers a rereading of Pierre
Bourdieu's classic work on forms of capital and their conversion. It emphasizes
the temporal dimension of capital accumulation and conversion and explores the
temporalities of online exchanges that have become constitutive of preacher
follower relationships. In doing so, it shows how Indonesia's Islamic preacher
economy is currently transformed by these online exchanges, resulting in preacher
follower relationships that are characterized by dialogic constructions of
Islamic authority. Being part of Indonesia's Islamic field, these changes in the
Islamic preacher economy point to a broader trend in Indonesia's Islamic field
toward greater sensitivity to the needs and worries of Indonesian middle-class
Muslims.
PMID- 28413809
TI - Preclinical imaging of iridocorneal angle and fundus using a modified integrated
flexible handheld probe.
AB - A flexible handheld imaging probe consisting of a [Formula: see text] charge
coupled device camera, light-emitting diode light sources, and near-infrared
laser source is designed and developed. The imaging probe is designed with
specifications to capture the iridocorneal angle images and posterior segment
images. Light propagation from the anterior chamber of the eye to the exterior is
considered analytically using Snell's law. Imaging of the iridocorneal angle
region and fundus is performed on ex vivo porcine samples and subsequently on
small laboratory animals, such as the New Zealand white rabbit and nonhuman
primate, in vivo. The integrated flexible handheld probe demonstrates high
repeatability in iridocorneal angle and fundus documentation. The proposed
concept and methodology are expected to find potential application in the
diagnosis, prognosis, and management of glaucoma.
PMID- 28413811
TI - Cell Surface Protein Detection to Assess Receptor Internalization.
AB - The migration of membrane receptors upon exposure to different
stimulants/inhibitors is of great importance. Among others, the internalization
of membrane receptors affects their accessibility to ligands and cell
responsiveness to environmental cues. Experimentally, receptor internalization
can be used as a measure of their activation. In our studies, we employed this
approach to explore cross-talk between a seven transmembrane domain receptor for
neuropeptide Y (NPY), Y5R, and a tyrosine kinase receptor for brain-derived
neurotrophic factor (BDNF), TrkB. To this end, we measured the internalization of
Y5R upon stimulation with the TrkB ligand, BDNF. Upon treatment with BDNF, the
cells were exposed to a membrane impermeable, biotinylation reagent that
selectively labels surface proteins. Subsequently, the biotinylated membrane
proteins were affinity-purified on columns with avidin resins and analyzed by
Western blot. Differences in the fraction of receptors present on the cell
surface of control and ligand-treated cells served as a measure of their
internalization and response to particular stimuli.
PMID- 28413812
TI - Quantitative 3D Time Lapse Imaging of Muscle Progenitors in Skeletal Muscle of
Live Mice.
AB - For non-optically clear mammalian tissues, it is now possible to use multi-photon
microscopy to penetrate deep into the tissue and obtain detailed single cell
images in a live animal, i.e., intravital imaging. This technique is in principle
applicable to any fluorescently marked cell, and we have employed it to observe
stem cells during the regenerative process. Stem cell-mediated skeletal muscle
regeneration in the mouse model has been classically studied at specific time
points by sacrificing the animal and harvesting the muscle tissue for downstream
analyses. A method for direct visualization of muscle stem cells to gain real
time information over a long period in a live mammal has been lacking. Here we
describe a step-by-step protocol adapted from Webster et al. (2016) to
quantitatively measure the behaviors of fluorescently labeled (GFP, EYFP) muscle
stem and progenitor cells during homeostasis as well as following muscle injury.
PMID- 28413815
TI - Data documenting the comparison between the theoretically expected values of free
sugars mass isotopomer composition with standards using GC-MS and LC-HRMS for
Metabolic Flux Analysis.
AB - The data presented in this article are related to the research article entitled
"13C labeling analysis of sugars by high resolution-mass spectrometry for
Metabolic Flux Analysis" (Acket et al., 2017) [1]. This article provides data
concerning the comparison between the theoretically expected values of free
sugars mass isotopomer composition with standards using our previous methods
using low resolution mass spectrometry by GC-MS (Koubaa et al., 2012, 2014)
[2,3], and your new method using high resolution-mass spectrometry (LC-HRMS) for
Metabolic Flux Analysis [1]. For discussion and a more comprehensive data
interpretation and analysis, please refer to Acket et al. (2017) [1].
PMID- 28413814
TI - Neural markers of individual differences in decision-making.
AB - In the last few years, neuroscientists have begun to identify associations
between individual differences in decision-making and features of neuroanatomy
and neurophysiology. Different tendencies in decision making, such as tolerance
for risk, delay or effort, have been linked to various neurobiological measures,
such as morphometry, structural connectivity, functional connectivity or the
function of neurotransmitter systems. Though far from immutable, these neural
features may nonetheless be suitable as relatively stable biomarkers for
different decision traits. The establishment of such markers would achieve one of
the stated goals of neuroeconomics, which is to improve the prediction of
economic behavior across different contexts.
PMID- 28413813
TI - New insights into early-life stress and behavioral outcomes.
AB - Adverse early-life experiences, including various forms of early-life stress,
have consistently been linked with vulnerability to cognitive and emotional
disorders later in life. Understanding the mechanisms underlying the enduring
consequences of early-life stress is an active area of research, because this
knowledge is critical for developing potential interventions. Animal models of
early-life stress typically rely on manipulating maternal/parental presence and
care, because these are the major source of early-life experiences in humans.
Diverse models have been created, and have resulted in a wealth of behavioral
outcomes. Here we focus on recent findings highlighting early-life stress-induced
behavioral disturbances, ranging from hippocampus-dependent memory deficits to
problems with experiencing pleasure (anhedonia). The use of naturalistic animal
models of chronic early-life stress provides insight into the spectrum of
cognitive and emotional outcomes and enables probing the underlying mechanisms
using molecular-, cellular-, and network-level approaches.
PMID- 28413816
TI - Spectroscopic and AFM characterization of polypeptide-surface interactions:
Controls and lipid quantitative analyses.
AB - This article is related to http://dx.doi.org/10.1016/j.bbamem.2017.01.005 (O.
Stromland, O.S. Handegard, M.L. Govasli, H. Wen, O. Halskau, 2017) [1]. In
protein and polypeptide-membrane interaction studies, negatively charged lipids
are often used as they are a known driver for membrane interaction. When using
fluorescence spectroscopy and CD as indicators of polypeptide binding and
conformational change, respectively, the effect of zwitterionic lipids only
should be documented. The present data documents several aspects of how two
engineered polypeptides (A-Cage-C and A-Lnk-C) derived from the membrane
associating protein alpha-Lactalbumin affects and are affected by the presence of
zwitterionic bilayers in the form of vesicles. We here document the behavior or
the Cage and Lnk segments with respect to membrane interaction and their residual
fold, using intrinsic tryptophan fluorescence assays. This data description also
documents the coverage of solid-supported bilayers prepared by spin-coating mica
using binary lipid mixes, a necessary step to ensure that AFM is performed on
areas that are covered by lipid bilayers when performing experiments. Uncovered
patches are detectable by both force curve measurements and height measurements.
We tested naked mica's ability to cause aggregation as seen by AFM, and found
this to be low compared to preparations containing negatively charged lipids.
Work with lipids also carries the risk of chemical degradation taking place
during vesicles preparation or other handling of the lipids. We therefor use 31P
NMR to quantify the head-group content of commonly used commercial extracts
before and after a standard protocol for vesicle production is applied.
PMID- 28413817
TI - Dataset in support of the generation of Niemann-Pick disease Type C1 patient
specific iPS cell lines carrying the novel NPC1 mutation c.1180T>C or the
prevalent c.3182T>C mutation - Analysis of pluripotency and neuronal
differentiation.
AB - Data presented in this article demonstrate the generation and characterization of
two novel Niemann-Pick disease Type C1 (NPC1) patient-specific induced
pluripotent stem cell (iPSC) lines, related to the research article Trilck et al.
(Diversity of Glycosphingolipid GM2 and Cholesterol Accumulation in NPC1 Patient
Specific iPSC-Derived Neurons; Brain Res.; 2017; 1657:52-61. doi:
10.1016/j.brainres.2016.11.031). For reprogramming fibroblasts, carrying the
novel homozygous mutation c.1180T>C and the prevalent homozygous mutation
c.3182T>C, were used. Reprogramming into patient-specific iPSCs was induced by
retroviral transduction of the transcription factors Sox2, Klf4, Oct4 and c-Myc,
and confirmed according to their pluripotency. The iPSCs were subsequently
differentiated into neural progenitor cells, which were terminally differentiated
into functional neurons and glial cells. The generation of these cell lines
provides further valuable tools to investigate pathogenic mechanism of NPC1 in
human neuronal cells carrying different NPC1 mutations.
PMID- 28413818
TI - Data on enhanced expression and purification of camelid single domain antibodies
from Escherichia coli classical inclusion bodies.
AB - Heterologous expression of high amounts of recombinant proteins is a milestone
for research and industrial purposes. Single domain antibodies (sdAbs) are heavy
chain only antibody fragments with applications in the biotechnological, medical
and industrial fields. The simple nature and small size of sdAbs allows for
efficient expression of the soluble molecule in different hosts. However, in some
cases, it results in low functional protein yield. To overcome this limitation,
expression of a 6xHistag sdAb was attempted in different conditions in
Escherichia coli BL21(DE3) cells. Data showed that high amount of sdAb can be
expressed in E. coli classical inclusion bodies, efficiently extracted by urea in
a short-time, and properly purified by metal ion affinity chromatography. These
data originate from the research article "Enhanced expression and purification of
camelid single domain VHH antibodies from classical inclusion bodies" Maggi and
Scotti (2017) [1] (DOI: http://dx.doi.org/10.1016/j.pep.2017.02.007).
PMID- 28413819
TI - Multisystemic Langerhans cell histiocytosis in an adult.
PMID- 28413820
TI - Coxsackievirus B5 associated with hand-foot-mouth disease in a healthy adult.
PMID- 28413821
TI - Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome.
AB - Down syndrome (DS), present in nearly six million people, is associated with an
extremely high risk to develop Alzheimer's disease (AD). Amyloid-beta and tau
pathology are omnipresent from age 40 years onward, but clinical symptoms do not
appear in all DS individuals. Dementia diagnostics is complex in this population,
illustrating the great need for predictive biomarkers. Although blood biomarkers
have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid
beta42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the
general population and are increasingly used in clinical practice. Surprisingly,
CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF
analyses would finally allow for the elucidation of its utility in (differential)
diagnoses and staging of disease severity. A sensitive and specific biomarker
profile for AD in DS would be of paramount importance to daily care, adaptive
caregiving, and specific therapeutic interventions.
PMID- 28413822
TI - Distinct Neural Properties in the Low-Frequency Region of the Chicken Cochlear
Nucleus Magnocellularis.
AB - Topography in the avian cochlear nucleus magnocellularis (NM) is represented as
gradually increasing characteristic frequency (CF) along the caudolateral-to
rostromedial axis. In this study, we characterized the organization and cell
biophysics of the caudolateral NM (NMc) in chickens (Gallus gallus). Examination
of cellular and dendritic architecture first revealed that NMc contains small
neurons and extensive dendritic processes, in contrast to adendritic, large
neurons located more rostromedially. Individual dye-filling study further
demonstrated that NMc is divided into two subregions, with NMc2 neurons having
larger and more complex dendritic fields than NMc1. Axonal tract tracing studies
confirmed that NMc1 and NMc2 neurons receive afferent inputs from the auditory
nerve and the superior olivary nucleus, similar to the adendritic NM. However,
the auditory axons synapse with NMc neurons via small bouton-like terminals,
unlike the large end bulb synapses on adendritic NM neurons. Immunocytochemistry
demonstrated that most NMc2 neurons express cholecystokinin but not calretinin,
distinct from NMc1 and adendritic NM neurons that are cholecystokinin negative
and mostly calretinin positive. Finally, whole-cell current clamp recordings
revealed that NMc neurons require significantly lower threshold current for
action potential generation than adendritic NM neurons. Moreover, in contrast to
adendritic NM neurons that generate a single-onset action potential, NMc neurons
generate multiple action potentials to suprathreshold sustained depolarization.
Taken together, our data indicate that NMc contains multiple neuron types that
are structurally, connectively, molecularly, and physiologically different from
traditionally defined NM neurons, emphasizing specialized neural properties for
processing low-frequency sounds.
PMID- 28413823
TI - Long-Term Predictive and Feedback Encoding of Motor Signals in the Simple Spike
Discharge of Purkinje Cells.
AB - Most hypotheses of cerebellar function emphasize a role in real-time control of
movements. However, the cerebellum's use of current information to adjust future
movements and its involvement in sequencing, working memory, and attention argues
for predicting and maintaining information over extended time windows. The
present study examines the time course of Purkinje cell discharge modulation in
the monkey (Macaca mulatta) during manual, pseudo-random tracking. Analysis of
the simple spike firing from 183 Purkinje cells during tracking reveals
modulation up to 2 s before and after kinematics and position error. Modulation
significance was assessed against trial shuffled firing, which decoupled simple
spike activity from behavior and abolished long-range encoding while preserving
data statistics. Position, velocity, and position errors have the most frequent
and strongest long-range feedforward and feedback modulations, with less common,
weaker long-term correlations for speed and radial error. Position, velocity, and
position errors can be decoded from the population simple spike firing with
considerable accuracy for even the longest predictive (-2000 to -1500 ms) and
feedback (1500 to 2000 ms) epochs. Separate analysis of the simple spike firing
in the initial hold period preceding tracking shows similar long-range
feedforward encoding of the upcoming movement and in the final hold period
feedback encoding of the just completed movement, respectively. Complex spike
analysis reveals little long-term modulation with behavior. We conclude that
Purkinje cell simple spike discharge includes short- and long-range
representations of both upcoming and preceding behavior that could underlie
cerebellar involvement in error correction, working memory, and sequencing.
PMID- 28413824
TI - Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic
Neuronal Circuitry.
AB - Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the
fine-tuning of neuron development and the establishment of wiring patterns in the
brain. However, whether serotonin is involved in the maintenance of neuronal
circuitry in the adult brain remains elusive. Here, we use a Tph2fl degrees x
conditional knockout (cKO) mouse line to assess the impact of serotonin depletion
during adulthood on serotonergic system organization. Data show that the density
of serotonergic fibers is increased in the hippocampus and decreased in the
thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin
depletion. Strikingly, these defects are rescued following reestablishment of
brain 5-HT signaling via administration of the serotonin precursor 5
hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers
reveals that changes in serotonin homeostasis affect axonal branching complexity.
These data demonstrate that maintaining proper serotonin homeostasis in the adult
brain is crucial to preserve the correct serotonergic axonal wiring.
PMID- 28413825
TI - Color-Change Detection Activity in the Primate Superior Colliculus.
AB - The primate superior colliculus (SC) is a midbrain structure that participates in
the control of spatial attention. Previous studies examining the role of the SC
in attention have mostly used luminance-based visual features (e.g., motion,
contrast) as the stimuli and saccadic eye movements as the behavioral response,
both of which are known to modulate the activity of SC neurons. To explore the
limits of the SC's involvement in the control of spatial attention, we recorded
SC neuronal activity during a task using color, a visual feature dimension not
traditionally associated with the SC, and required monkeys to detect threshold
level changes in the saturation of a cued stimulus by releasing a joystick during
maintained fixation. Using this color-based spatial attention task, we found
substantial cue-related modulation in all categories of visually responsive
neurons in the intermediate layers of the SC. Notably, near-threshold changes in
color saturation, both increases and decreases, evoked phasic bursts of activity
with magnitudes as large as those evoked by stimulus onset. This change-detection
activity had two distinctive features: activity for hits was larger than for
misses, and the timing of change-detection activity accounted for 67% of joystick
release latency, even though it preceded the release by at least 200 ms. We
conclude that during attention tasks, SC activity denotes the behavioral
relevance of the stimulus regardless of feature dimension and that phasic event
related SC activity is suitable to guide the selection of manual responses as
well as saccadic eye movements.
PMID- 28413826
TI - Medial Ganglionic Eminence Progenitors Transplanted into Hippocampus Integrate in
a Functional and Subtype-Appropriate Manner.
AB - Medial ganglionic eminence (MGE) transplantation rescues disease phenotypes in
various preclinical models with interneuron deficiency or dysfunction, including
epilepsy. While underlying mechanism(s) remains unclear to date, a simple
explanation is that appropriate synaptic integration of MGE-derived interneurons
elevates GABA-mediated inhibition and modifies the firing activity of excitatory
neurons in the host brain. However, given the complexity of interneurons and
potential for transplant-derived interneurons to integrate or alter the host
network in unexpected ways, it remains unexplored whether synaptic connections
formed by transplant-derived interneurons safely mirror those associated with
endogenous interneurons. Here, we combined optogenetics, interneuron-specific Cre
driver mouse lines, and electrophysiology to study synaptic integration of MGE
progenitors. We demonstrated that MGE-derived interneurons, when transplanted
into the hippocampus of neonatal mice, migrate in the host brain, differentiate
to mature inhibitory interneurons, and form appropriate synaptic connections with
native pyramidal neurons. Endogenous and transplant-derived MGE progenitors
preferentially formed inhibitory synaptic connections onto pyramidal neurons but
not endogenous interneurons. These findings demonstrate that transplanted MGE
progenitors functionally integrate into the postnatal hippocampal network.
PMID- 28413827
TI - A Balanced Comparison of Object Invariances in Monkey IT Neurons.
AB - Our ability to recognize objects across variations in size, position, or rotation
is based on invariant object representations in higher visual cortex. However, we
know little about how these invariances are related. Are some invariances harder
than others? Do some invariances arise faster than others? These comparisons can
be made only upon equating image changes across transformations. Here, we
targeted invariant neural representations in the monkey inferotemporal (IT)
cortex using object images with balanced changes in size, position, and rotation.
Across the recorded population, IT neurons generalized across size and position
both stronger and faster than to rotations in the image plane as well as in
depth. We obtained a similar ordering of invariances in deep neural networks but
not in low-level visual representations. Thus, invariant neural representations
dynamically evolve in a temporal order reflective of their underlying
computational complexity.
PMID- 28413829
TI - Prioritizing US Cervical Cancer Prevention With Results From a Geospatial Model.
AB - PURPOSE: To determine if differences in screening and vaccination patterns across
the population may accentuate ethnic and geographic variation in future burden of
disease. METHODS: Using Cancer in North America data provided by the North
American Association of Central Cancer Registries, county cervical cancer
incidence trends from 1995 to 2009 were modeled for the entire United States
using ecologic covariates. Rates for health service areas were also modeled by
ethnicity. State-level incidence was mapped together with Papanicolaou (Pap)
screening, past 3 years (women >= 18 years old), and three-dose human
papillomavirus (HPV) vaccine coverage (girls 13 to 17 years old) to identify
potential priority areas for preventive services. RESULTS: US cervical cancer
incidence decreased more during the periods 1995 to 1999 and 2000 to 2004 than
during the period 2005 to 2009. During these 15 years, the most affected areas
became increasingly confined to Appalachia, the lower Mississippi Valley, the
Deep South, Texas, and Florida. Hispanic and black women experienced a higher
incidence of cervical cancer than both white and Asian and Pacific Islander women
during each period. Women in 10 of 17 states/districts with a high incidence (>=
8.14/100,000) reported low Pap testing (< 78.5%), HPV vaccine coverage (< 33.9%),
or both prevention technologies. CONCLUSION: The decline in cervical cancer
incidence has slowed in recent years. Access to HPV vaccination, targeted
screening, and treatment in affected populations is needed to reduce cervical
cancer disparities in the future.
PMID- 28413830
TI - An observational study on surgically treated adult idiopathic scoliosis patients'
quality of life outcomes at 1- and 2-year follow-ups and comparison to controls.
AB - BACKGROUND: Prospective data on health-related quality of life in patients with
idiopathic scoliosis treated surgically as adults is needed. We compared
preoperative and 1- and 2-year follow-up data in surgically treated adults with
idiopathic scoliosis with juvenile or adolescent onset. Results were compared to
untreated adults with scoliosis and population normative data. METHODS: A
comparison of preoperative and 1- and 2-year follow-up data of 75 adults
surgically treated for idiopathic scoliosis at a mean age of 28 years (range 18
to 69) from a prospective national register study, as well as a comparison with
age- and sex-matched data from 75 untreated adults with less severe scoliosis and
75 adults without scoliosis, was made. Outcome measures were EuroQol-5 dimensions
(EQ-5D) and Scoliosis Research Society (SRS)-22r questionnaire. RESULTS: In the
surgically treated, EQ-5D and SRS-22r scores had statistically significant
improvements at both 1- and 2-year follow-ups (all p < 0.015). The effect size
of surgery on EQ-5D at 1-year follow-up was large (r = -0.54) and small-medium (r
= -0.20) at 2-year follow-up. The effect size of surgery on SRS-22r outcomes was
medium-large at 1- and 2-year follow-ups (r = -0.43 and r = -0.42 respectively).
At the 2-year follow-up, the EQ-5D score and the SRS-22r subscore were similar to
the untreated scoliosis group (p = 0.56 and p = 0.91 respectively), but lower
than those in the adults without scoliosis (p < 0.001 for both comparisons).
CONCLUSIONS: Adults with idiopathic scoliosis experience an increase in health
related quality of life following surgery at 2-year follow-up, approaching the
health-related quality of life of untreated individuals with less severe
scoliosis, but remain lower than normative population data.
PMID- 28413828
TI - Functions and Mechanisms of Sleep.
AB - Sleep is a complex physiological process that is regulated globally, regionally,
and locally by both cellular and molecular mechanisms. It occurs to some extent
in all animals, although sleep expression in lower animals may be co-extensive
with rest. Sleep regulation plays an intrinsic part in many behavioral and
physiological functions. Currently, all researchers agree there is no single
physiological role sleep serves. Nevertheless, it is quite evident that sleep is
essential for many vital functions including development, energy conservation,
brain waste clearance, modulation of immune responses, cognition, performance,
vigilance, disease, and psychological state. This review details the
physiological processes involved in sleep regulation and the possible functions
that sleep may serve. This description of the brain circuitry, cell types, and
molecules involved in sleep regulation is intended to further the reader's
understanding of the functions of sleep.
PMID- 28413831
TI - Differential ability of the dorsal and ventral rat hippocampus to exhibit group I
metabotropic glutamate receptor-dependent synaptic and intrinsic plasticity.
AB - BACKGROUND: The hippocampus is critically involved in learning and memory
processes. Although once considered a relatively homogenous structure, it is now
clear that the hippocampus can be divided along its longitudinal axis into
functionally distinct domains, responsible for the encoding of different types of
memory or behaviour. Although differences in extrinsic connectivity are likely to
contribute to this functional differentiation, emerging evidence now suggests
that cellular and molecular differences at the level of local hippocampal
circuits may also play a role. METHODS: In this study, we have used extracellular
field potential recordings to compare basal input/output function and group I
metabotropic glutamate receptor-dependent forms of synaptic and intrinsic
plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the
adult rat hippocampus. RESULTS: Using two extracellular electrodes to
simultaneously record field EPSPs and population spikes, we show that dorsal and
ventral hippocampal slices differ in their basal levels of excitatory synaptic
transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore,
we show that slices taken from the ventral hippocampus have a greater ability
than their dorsal counterparts to exhibit long-term depression of synaptic
transmission and EPSP-to-Spike potentiation induced by transient application of
the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine. CONCLUSIONS: Together,
our results provide further evidence that the information processing properties
of local hippocampal circuits differ in the dorsal and ventral hippocampal
sectors, and that these differences may in turn contribute to the functional
differentiation that exists along the hippocampal longitudinal axis.
PMID- 28413832
TI - Statistical analysis plan for the WOMAN-ETAPlaT study: Effect of tranexamic acid
on platelet function and thrombin generation.
AB - Background. Postpartum haemorrhage (PPH) is a potentially life-threatening
complication for women, and the leading cause of maternal mortality. Tranexamic
acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and
to reduce blood loss in general surgery. TXA may have effects on thrombin
generation, platelet function and coagulation factors as a result of its
inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World
Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically
diagnosed with PPH after a vaginal delivery or caesarean section, are eligible
for inclusion in the study. Blood samples will be collected at the baseline and
30 minutes after the first dose of study treatment is given. Platelet function
will be evaluated in whole blood immediately after sampling with Multiplate(r)
tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and
coagulation factors vW, V and VIII will be analysed using platelet poor plasma.
Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on
13 January 2015, during this time 188 patients were recruited. The final
participant follow-up was completed on 04 March 2015. This article introduces the
statistical analysis plan for the study, without reference to unblinded data.
Conclusion. The data from this study will provide evidence for the effect of TXA
on thrombin generation, platelet function and coagulation factors in women with
PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469;
ISRCTN76912190.
PMID- 28413834
TI - Synthesis and characterization of zinc oxide thin films for optoelectronic
applications.
AB - Micro-ring structured zinc oxide (ZnO) thin films were prepared on glass
substrates by spray pyrolysis and their structural, morphological, optical and
electrical properties were investigated. X-ray Diffraction (XRD) analysis
revealed the films' hexagonal wurtzite phase with a preferred (002) grain
orientation. The mean crystallite size calculated on the basis of the Debye
Scherrer model was 24 nm and a small dislocation density of [Formula: see text]
was obtained, indicating the existence of few lattice defects and good
crystallinity. Scanning Electron Microscopy (SEM) micrographs revealed the film's
granular nature composed of rod-shaped and spherical nanoparticles which
agglomerated to form micro-ring like film clusters on the film surface. The
average transmittance in the visible region, optical band gap and Urbach energy
were approximately 75-80%, 3.28 eV and 57 meV, respectively. The refractive index
and extinction coefficient were determined using Swanepoel's envelope method.
Raman spectroscopy revealed the presence of small amounts of residual tensile
stress and low density of defects in the ZnO thin films. This was consistent with
XRD analysis. A low sheet resistivity [Formula: see text] and high figure of
merit [Formula: see text] were obtained for our films indicating their
suitability in optoelectronic applications.
PMID- 28413833
TI - Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on
motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse
model of Alzheimer's disease.
AB - Alzheimer's disease (AD), a progressive neurodegenerative disorder, is linked to
oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau
hyperphosphorylation and the accumulation of amyloid-beta (Abeta) plaques and
neurofibrillary tangles (NFT). A growing body of evidence suggests that
mitochondrial dysfunction can be a key promoter of all of these pathologies and
predicts that restoration of mitochondrial function might be a potential
therapeutic strategy for AD. Therefore, in the present study, we tested the
beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II),
containing NT020 (a mitochondrial restorative and antioxidant proprietary
formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria
biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks,
starting at 3 months of age, after which behavioral and neuropathological
endpoints were determined. The data from behavioral test batteries clearly
revealed that dietary supplementation of Nutra II effectively ameliorated the
motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II
also protected mitochondrial function in 5XFAD mice brain, as evidenced by
declined ROS levels and membrane hyperpolarization, together with elevated ATP
levels and respiratory states. Interestingly, while Nutra II treatment only
slightly reduced soluble Abeta42 levels, this formulation significantly impacted
tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD
mouse brain. Taken together, these preclinical findings confirm that
mitochondrial function may be a key treatment target for AD and that Nutra II
should be further investigated as a potential candidate for AD therapy.
PMID- 28413836
TI - Assessment of the perceived effects and management challenges of Mikania
micrantha invasion in Chitwan National Park buffer zone community forest, Nepal.
AB - The effects of invasion by Mikania micrantha in the buffer zone of Chitwan
National Park (CNP) of Nepal are well documented; however the studies were
confined to appraising the perception of household and did not assess the changes
in livelihood activities after the invasion. This study presents the effects of
invasion of M. micrantha on the livelihood of buffer zone of the Chitwan National
Park; hence addressing the gap in information and shows the complex effect of M.
micrantha on rural livelihood. The study used a questionnaire survey to 170
households in the CNP of Nepal. The results indicate that the invasion of M.
micrantha have negative effects on the community livelihood in the study area.
Basic forest products such as fodder and fuel wood have become scarce as a result
of reduction in the native plants. Also the spread of M. micrantha is creating
impassable copse that destroy wildlife abode and jungle paths resulting into
animals to shift their habitat to core area thereby reducing tourism revenues.
Therefore, the study concludes that invasion of M. micrantha directly or
indirectly is modifying the rural household livelihoods and a quick action is
stipulated. Hence, a higher level body like the Ministry of Forestry or
Department of National Park and Wildlife Conservation needs to take care of
issues related to alien species. Correspondingly, it is also very important that
people are aware and educated about alien species and their effects.
PMID- 28413835
TI - miRNA signatures can predict acute liver failure in hepatitis E infected pregnant
females.
AB - BACKGROUND: Acute viral hepatitis E (AVH-E) can often result in acute liver
failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced
liver failure. We investigated their role as a biomarker in predicting ALF due to
HEV (ALF-E). METHODS: We performed next generation sequencing and subsequent
validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV
(ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy
controls. FINDINGS: Eleven microRNAs were significantly expressed in response to
HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly
expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but
not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting
AVH-E in pregnant females. miR-450b which affects cellular proliferation and
metabolic processes through RNF20 and SECB was predominanlty upregulated and
correlated with poor outcome (ROC 0.958, p = 0.001). INTERPRETATION: Our results
reveal that a specific microRNA profile can predict fatality in ALF-E in
pregnancy. These microRNAs could be exploited as prognostic biomarkers and help
in the development of new therapeutic interventions.
PMID- 28413837
TI - Familial exudative vitreoretinopathy presentation as persistent fetal
vasculature.
AB - PURPOSE: To illustrate a presentation of familial exudative vitreoretinopathy
(FEVR) that can be mistaken for unilateral persistent fetal vasculature (PFV) and
the importance of wide angle fluorescein angiography in making this distinction.
A patient was referred with a unilateral retrolental membrane and retinal
detachment from PFV but was found to have FEVR. OBSERVATIONS: A 4 month-old full
term infant was referred with the diagnosis of PFV based on findings of a dense
retrolental membrane and microphthalmia in the left eye. The patient had a near
complete retinal detachment with some exudation. Wide-field fluorescein
angiography of the right eye revealed avascular retina and leakage at the
vascular/avascular junction. Genetic testing confirmed a mutation in FZD4,
supporting the clinical diagnosis of FEVR. Prompt laser therapy to the avascular
area in the right eye was performed and lensectomy/vitrectomy with membrane
dissection was performed in the left eye. CONCLUSIONS AND IMPORTANCE: FEVR can
present with great variability between eyes. In patients presenting with findings
suggestive of PFV, careful bilateral examination with wide-field fluorescein
angiography is helpful. Early diagnosis and treatment are important to preserve
visual acuity, especially in the less affected eye.
PMID- 28413838
TI - Advanced structural multimodal imaging of a patient with subcortical band
heterotopia.
AB - Subcortical band heterotopia (SBH) is a disorder of neuronal migration most
commonly due to mutations of the Doublecortin (DCX) gene. A range of phenotypes
is seen, with most patients having some degree of epilepsy and intellectual
disability. Advanced diffusion and structural magnetic resonance imaging (MRI)
sequences may be useful in identifying heterotopias and dysplasias of different
sizes in drug-resistant epilepsy. We describe a patient with SBH and drug
resistant epilepsy and investigate neurite density, neurite dispersion, and
diffusion parameters as compared to a healthy control through the use of multiple
advanced MRI modalities. Neurite density and dispersion in heterotopia was found
to be more similar to white matter than gray matter. Neurite density and
dispersion maps obtained using diffusion imaging may be able to better
characterize different subtypes of heterotopia.
PMID- 28413839
TI - Modeling Reusable and Interoperable Faceted Browsing Systems with Category
Theory.
AB - Faceted browsing has become ubiquitous with modern digital libraries and online
search engines, yet the process is still difficult to abstractly model in a
manner that supports the development of interoperable and reusable interfaces. We
propose category theory as a theoretical foundation for faceted browsing and
demonstrate how the interactive process can be mathematically abstracted.
Existing efforts in facet modeling are based upon set theory, formal concept
analysis, and lightweight ontologies, but in many regards, they are
implementations of faceted browsing rather than a specification of the basic,
underlying structures and interactions. We will demonstrate that category theory
allows us to specify faceted objects and study the relationships and interactions
within a faceted browsing system. Implementations can then be constructed through
a category-theoretic lens using these models, allowing abstract comparison and
communication that naturally support interoperability and reuse.
PMID- 28413840
TI - Modeling Integration and Reuse of Heterogeneous Terminologies in Faceted Browsing
Systems.
AB - We integrate heterogeneous terminologies into our category-theoretic model of
faceted browsing and show that existing terminologies and vocabularies can be
reused as facets in a cohesive, interactive system. Commonly found in online
search engines and digital libraries, faceted browsing systems depend upon one or
more taxonomies which outline the structure and content of the facets available
for user interaction. Controlled vocabularies or terminologies are often
externally curated and are available as a reusable resource across systems. We
demonstrated previously that category theory can abstractly model faceted
browsing in a way that supports the development of interfaces capable of reusing
and integrating multiple models of faceted browsing. We extend this model by
illustrating that terminologies can be reused and integrated as facets across
systems with examples from the biomedical domain.
PMID- 28413841
TI - Correlation of electrode position and clinical outcomes in globus pallidus
stimulation for dystonia.
AB - BACKGROUND: The correlation between the electrode location and the clinical
outcome for internal globus pallidus (GPi) deep brain stimulation (DBS) has not
been fully elucidated. OBJECTIVE: The aim of this study was to determine the
discrepancies between the theoretical target planned by magnetic resonance
imaging (MRI) and the actual electrode location in postoperative MRI, as well as
to find the correlation between the final electrode locations and the clinical
outcome after GPi DBS. METHODS: Thirty-six patients who underwent GPi DBS for
dystonia were included in this retrospective study. The X coordinate was defined
as the lateral distance from the midline, the Y coordinate as the anterior
distance from the midcommissural point, and the Z coordinate as the inferior
distance from the intercommissural line. RESULTS: All coordinates showed a
significant difference between theoretical and actual values for all electrode
locations (p < 0.05). In particular, greater differences were exhibited for Y
than for the X and Z coordinates. There was no significant difference in the
accuracy of the localization of the left-side versus the right-side electrode for
any coordinates. The patients whose electrodes were located within or near the
posteroventral GPi showed better clinical outcomes. CONCLUSIONS: The actual
electrode location was slightly more posterior to the theoretically planned
target. Electrodes concentrated near the posteroventral GPi tended to yield
favorable outcomes.
PMID- 28413842
TI - "I do not have time. Is there a handout I can use?": combining physicians' needs
and behavior change theory to put physical activity evidence into practice.
AB - : Guidelines for physical activity exist and following them would improve health.
Physicians can advise patients on physical activity. We found barriers related to
physicians' knowledge, a lack of tools and of physician incentives, and competing
demands for limited time with a patient. We discuss interventions that could
reduce these barriers. INTRODUCTION: Uptake of physical activity (PA) guidelines
would improve health and reduce mortality in older adults. However, physicians
face barriers in guideline implementation, particularly when faced with needing
to tailor recommendations in the presence of chronic disease. We performed a
behavioral analysis of physician barriers to PA guideline implementation and to
identify interventions. The Too Fit To Fracture physical activity recommendations
were used as an example of disease-specific PA guidelines. METHODS: Focus groups
and semi-structured interviews were conducted with physicians and nurse
practitioners in Ontario, stratified by type of physician, geographic area, and
urban/rural, and transcribed verbatim. Two researchers coded data and identified
emerging themes. Using the behavior change wheel framework, themes were
categorized into capability, opportunity and motivation, and interventions were
identified. RESULTS: Fifty-nine family physicians, specialists, and nurse
practitioners participated. Barriers were as follows: Capability-lack of exercise
knowledge or where to refer; Opportunity-pragmatic tools, fit within existing
workflow, available programs that meet patients' needs, physical activity
literacy and cultural practices; Motivation-lack of incentives, not in their
scope of practice or professional identity, competing priorities, outcome
expectancies. Interventions selected: education, environmental restructuring,
enablement, persuasion. Policy categories: communications/marketing, service
provision, guidelines. CONCLUSIONS: Key barriers to PA guideline implementation
among physicians include knowledge on where to refer or what to say, access to
pragmatic programs or resources, and things that influence motivation, such as
competing priorities or lack of incentives. Future work will report on the
development and evaluation of knowledge translation interventions informed by the
barriers.
PMID- 28413843
TI - Methodology Used to Assess Acceptability of Oral Pediatric Medicines: A
Systematic Literature Search and Narrative Review.
AB - BACKGROUND: Regulatory guidelines require that any new medicine designed for a
pediatric population must be demonstrated as being acceptable to that population.
There is currently no guidance on how to conduct or report on acceptability
testing. AIM: Our objective was to undertake a review of the methods used to
assess the acceptability of medicines within a pediatric population and use this
review to propose the most appropriate methodology. METHODS: We used a defined
search strategy to identify literature reports of acceptability assessments of
medicines conducted within pediatric populations and extracted information about
the tools used in these studies for comparison across studies. RESULTS: In total,
61 articles were included in the analysis. Palatability was the most common
(54/61) attribute measured when evaluating acceptability. Simple scale methods
were most commonly used, with visual analog scales (VAS) and hedonic scales used
both separately and in combination in 34 of the 61 studies. Hedonic scales alone
were used in 14 studies and VAS alone in just five studies. Other tools included
Likert scales; forced choice or preference; surveys or questionnaires;
observations of facial expressions during administration, ease of swallowing, or
ability to swallow the dosage; prevalence of complaints or refusal to take the
medicine; and time taken for a nurse to administer the medicine. CONCLUSIONS: The
best scale in terms of validity, reliability, feasibility, and preference to use
when assessing acceptability remains unclear. Further work is required to select
the most appropriate method to justify whether a medicine is acceptable to a
pediatric population.
PMID- 28413844
TI - Organo-axial volvulus of the small intestine: radiological case report and
consideration for its mechanism.
AB - Gastrointestinal volvulus is mainly classified into two subtypes, mesentero-axial
volvulus and organo-axial volvulus. The detailed imaging findings of organo-axial
volvulus of the small intestine have never been reported as far as we know. In
this article, we report a case of organo-axial volvulus of the small intestine,
focusing on the computed tomography (CT) findings. An 80-year-old man was
radiologically diagnosed as having organo-axial volvulus of the terminal ileum
and it was confirmed by open surgery without adhesion or any other anatomical
abnormalities. CT showed two specific findings, split-bowel sign and rotating-C
sign, which we think reflect pathophysiologic features of organo-axial volvulus.
We think the pathogenic mechanism of organo-axial volvulus can be explained by
the convergence of the reversed-rotational twist following the formation of a
twisted but non-obstructive circular loop, even if there is no adhesion.
Radiologists should be aware that organo-axial volvulus can occur even in the
small intestine, and in the case of small bowel obstruction with single
transition point, the two pathophysiologic signs mentioned above must be looked
for to diagnose the possibility of organo-axial volvulus.
PMID- 28413845
TI - Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon
emissions.
AB - BACKGROUND: Several independent lines of evidence suggest that Amazon forests
have provided a significant carbon sink service, and also that the Amazon carbon
sink in intact, mature forests may now be threatened as a result of different
processes. There has however been no work done to quantify non-land-use-change
forest carbon fluxes on a national basis within Amazonia, or to place these
national fluxes and their possible changes in the context of the major
anthropogenic carbon fluxes in the region. Here we present a first attempt to
interpret results from ground-based monitoring of mature forest carbon fluxes in
a biogeographically, politically, and temporally differentiated way.
Specifically, using results from a large long-term network of forest plots, we
estimate the Amazon biomass carbon balance over the last three decades for the
different regions and nine nations of Amazonia, and evaluate the magnitude and
trajectory of these differentiated balances in relation to major national
anthropogenic carbon emissions. RESULTS: The sink of carbon into mature forests
has been remarkably geographically ubiquitous across Amazonia, being substantial
and persistent in each of the five biogeographic regions within Amazonia. Between
1980 and 2010, it has more than mitigated the fossil fuel emissions of every
single national economy, except that of Venezuela. For most nations (Bolivia,
Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably
additionally mitigated all anthropogenic carbon emissions due to Amazon
deforestation and other land use change. While the sink has weakened in some
regions since 2000, our analysis suggests that Amazon nations which are able to
conserve large areas of natural and semi-natural landscape still contribute
globally-significant carbon sequestration. CONCLUSIONS: Mature forests across all
of Amazonia have contributed significantly to mitigating climate change for
decades. Yet Amazon nations have not directly benefited from providing this
global scale ecosystem service. We suggest that better monitoring and reporting
of the carbon fluxes within mature forests, and understanding the drivers of
changes in their balance, must become national, as well as international,
priorities.
PMID- 28413846
TI - A carbon balance model for the great dismal swamp ecosystem.
AB - BACKGROUND: Carbon storage potential has become an important consideration for
land management and planning in the United States. The ability to assess
ecosystem carbon balance can help land managers understand the benefits and
tradeoffs between different management strategies. This paper demonstrates an
application of the Land Use and Carbon Scenario Simulator (LUCAS) model developed
for local-scale land management at the Great Dismal Swamp National Wildlife
Refuge. We estimate the net ecosystem carbon balance by considering past
ecosystem disturbances resulting from storm damage, fire, and land management
actions including hydrologic inundation, vegetation clearing, and replanting.
RESULTS: We modeled the annual ecosystem carbon stock and flow rates for the 30
year historic time period of 1985-2015, using age-structured forest growth curves
and known data for disturbance events and management activities. The 30-year
total net ecosystem production was estimated to be a net sink of 0.97 Tg C. When
a hurricane and six historic fire events were considered in the simulation, the
Great Dismal Swamp became a net source of 0.89 Tg C. The cumulative above and
below-ground carbon loss estimated from the South One and Lateral West fire
events totaled 1.70 Tg C, while management activities removed an additional 0.01
Tg C. The carbon loss in below-ground biomass alone totaled 1.38 Tg C, with the
balance (0.31 Tg C) coming from above-ground biomass and detritus. CONCLUSIONS:
Natural disturbances substantially impact net ecosystem carbon balance in the
Great Dismal Swamp. Through alternative management actions such as re-wetting,
below-ground biomass loss may have been avoided, resulting in the added carbon
storage capacity of 1.38 Tg. Based on two model assumptions used to simulate the
peat system, (a burn scar totaling 70 cm in depth, and the soil carbon
accumulation rate of 0.36 t C/ha-1/year-1 for Atlantic white cedar), the total
soil carbon loss from the South One and Lateral West fires would take
approximately 1740 years to re-amass. Due to the impractical time horizon this
presents for land managers, this particular loss is considered permanent. Going
forward, the baseline carbon stock and flow parameters presented here will be
used as reference conditions to model future scenarios of land management and
disturbance.
PMID- 28413847
TI - Greenhouse gas emissions from tropical forest degradation: an underestimated
source.
AB - BACKGROUND: The degradation of forests in developing countries, particularly
those within tropical and subtropical latitudes, is perceived to be an important
contributor to global greenhouse gas emissions. However, the impacts of forest
degradation are understudied and poorly understood, largely because international
emission reduction programs have focused on deforestation, which is easier to
detect and thus more readily monitored. To better understand and seize
opportunities for addressing climate change it will be essential to improve
knowledge of greenhouse gas emissions from forest degradation. RESULTS: Here we
provide a consistent estimation of forest degradation emissions between 2005 and
2010 across 74 developing countries covering 2.2 billion hectares of forests. We
estimated annual emissions of 2.1 billion tons of carbon dioxide, of which 53%
were derived from timber harvest, 30% from woodfuel harvest and 17% from forest
fire. These percentages differed by region: timber harvest was as high as 69% in
South and Central America and just 31% in Africa; woodfuel harvest was 35% in
Asia, and just 10% in South and Central America; and fire ranged from 33% in
Africa to only 5% in Asia. Of the total emissions from deforestation and forest
degradation, forest degradation accounted for 25%. In 28 of the 74 countries,
emissions from forest degradation exceeded those from deforestation. CONCLUSIONS:
The results of this study clearly demonstrate the importance of accounting
greenhouse gases from forest degradation by human activities. The scale of
emissions presented indicates that the exclusion of forest degradation from
national and international GHG accounting is distorting. This work helps identify
where emissions are likely significant, but policy developments are needed to
guide when and how accounting should be undertaken. Furthermore, ongoing research
is needed to create and enhance cost-effective accounting approaches.
PMID- 28413848
TI - Impact of data model and point density on aboveground forest biomass estimation
from airborne LiDAR.
AB - BACKGROUND: Accurate estimation of aboveground forest biomass (AGB) and its
dynamics is of paramount importance in understanding the role of forest in the
carbon cycle and the effective implementation of climate change mitigation
policies. LiDAR is currently the most accurate technology for AGB estimation.
LiDAR metrics can be derived from the 3D point cloud (echo-based) or from the
canopy height model (CHM). Different sensors and survey configurations can affect
the metrics derived from the LiDAR data. We evaluate the ability of the metrics
derived from the echo-based and CHM data models to estimate AGB in three
different biomes, as well as the impact of point density on the metrics derived
from them. RESULTS: Our results show that differences among metrics derived at
different point densities were significantly different from zero, with a larger
impact on CHM-based than echo-based metrics, particularly when the point density
was reduced to 1 point m-2. Both data models-echo-based and CHM-performed
similarly well in estimating AGB at the three study sites. For the temperate
forest in the Sierra Nevada Mountains, California, USA, R2 ranged from 0.79 to
0.8 and RMSE (relRMSE) from 69.69 (35.59%) to 70.71 (36.12%) Mg ha-1 for the echo
based model and from 0.76 to 0.78 and 73.84 (37.72%) to 128.20 (65.49%) Mg ha-1
for the CHM-based model. For the moist tropical forest on Barro Colorado Island,
Panama, the models gave R2 ranging between 0.70 and 0.71 and RMSE between 30.08
(12.36%) and 30.32 (12.46) Mg ha-1 [between 0.69-0.70 and 30.42 (12.50%) and
61.30 (25.19%) Mg ha-1] for the echo-based [CHM-based] models. Finally, for the
Atlantic forest in the Sierra do Mar, Brazil, R2 was between 0.58-0.69 and RMSE
between 37.73 (8.67%) and 39.77 (9.14%) Mg ha-1 for the echo-based model, whereas
for the CHM R2 was between 0.37-0.45 and RMSE between 45.43 (10.44%) and 67.23
(15.45%) Mg ha-1. CONCLUSIONS: Metrics derived from the CHM show a higher
dependence on point density than metrics derived from the echo-based data model.
Despite the median of the differences between metrics derived at different point
densities differing significantly from zero, the mean change was close to zero
and smaller than the standard deviation except for very low point densities (1
point m-2). The application of calibrated models to estimate AGB on metrics
derived from thinned datasets resulted in less than 5% error when metrics were
derived from the echo-based model. For CHM-based metrics, the same level of error
was obtained for point densities higher than 5 points m-2. The fact that reducing
point density does not introduce significant errors in AGB estimates is important
for biomass monitoring and for an effective implementation of climate change
mitigation policies such as REDD + due to its implications for the costs of data
acquisition. Both data models showed similar capability to estimate AGB when
point density was greater than or equal to 5 point m-2.
PMID- 28413849
TI - From berries to blocks: carbon stock quantification of a California vineyard.
AB - BACKGROUND: Quantifying terrestrial carbon (C) stocks in vineyards represents an
important opportunity for estimating C sequestration in perennial cropping
systems. Considering 7.2 M ha are dedicated to winegrape production globally, the
potential for annual C capture and storage in this crop is of interest to
mitigate greenhouse gas emissions. In this study, we used destructive sampling to
measure C stocks in the woody biomass of 15-year-old Cabernet Sauvignon vines
from a vineyard in California's northern San Joaquin Valley. We characterize C
stocks in terms of allometric variation between biomass fractions of roots,
aboveground wood, canes, leaves and fruits, and then test correlations between
easy-to-measure variables such as trunk diameter, pruning weights and harvest
weight to vine biomass fractions. Carbon stocks at the vineyard block scale were
validated from biomass mounds generated during vineyard removal. RESULTS: Total
vine C was estimated at 12.3 Mg C ha-1, of which 8.9 Mg C ha-1 came from
perennial vine biomass. Annual biomass was estimated at 1.7 Mg C ha-1 from leaves
and canes and 1.7 Mg C ha-1 from fruit. Strong, positive correlations were found
between the diameter of the trunk and overall woody C stocks (R2 = 0.85), pruning
weights and leaf and fruit C stocks (R2 = 0.93), and between fruit weight and
annual C stocks (R2 = 0.96). CONCLUSIONS: Vineyard C partitioning obtained in
this study provides detailed C storage estimations in order to understand the
spatial and temporal distribution of winegrape C. Allometric equations based on
simple and practical biomass and biometric measurements could enable winegrape
growers to more easily estimate existing and future C stocks by scaling up from
berries and vines to vineyard blocks.
PMID- 28413850
TI - Scenarios in tropical forest degradation: carbon stock trajectories for REDD.
AB - BACKGROUND: Human-caused disturbance to tropical rainforests-such as logging and
fire-causes substantial losses of carbon stocks. This is a critical issue to be
addressed in the context of policy discussions to implement REDD+. This work
reviews current scientific knowledge about the temporal dynamics of degradation
induced carbon emissions to describe common patterns of emissions from logging
and fire across tropical forest regions. Using best available information, we:
(i) develop short-term emissions factors (per area) for logging and fire
degradation scenarios in tropical forests; and (ii) describe the temporal pattern
of degradation emissions and recovery trajectory post logging and fire
disturbance. RESULTS: Average emissions from aboveground biomass were 19.9 MgC/ha
for logging and 46.0 MgC/ha for fire disturbance, with an average period of study
of 3.22 and 2.15 years post-disturbance, respectively. Longer-term studies of
post-logging forest recovery suggest that biomass accumulates to pre-disturbance
levels within a few decades. Very few studies exist on longer-term (>10 years)
effects of fire disturbance in tropical rainforests, and recovery patterns over
time are unknown. CONCLUSIONS: This review will aid in understanding whether
degradation emissions are a substantial component of country-level emissions
portfolios, or whether these emissions would be offset by forest recovery and
regeneration.
PMID- 28413851
TI - Detecting peatland drains with Object Based Image Analysis and Geoeye-1 imagery.
AB - BACKGROUND: Peatlands play an important role in the global carbon cycle. They
provide important ecosystem services including carbon sequestration and storage.
Drainage disturbs peatland ecosystem services. Mapping drains is difficult and
expensive and their spatial extent is, in many cases, unknown. An object based
image analysis (OBIA) was performed on a very high resolution satellite image
(Geoeye-1) to extract information about drain location and extent on a blanket
peatland in Ireland. Two accuracy assessment methods: Error matrix and the
completeness, correctness and quality (CCQ) were used to assess the extracted
data across the peatland and at several sub sites. The cost of the OBIA method
was compared with manual digitisation and field survey. The drain maps were also
used to assess the costs relating to blocking drains vs. a business-as-usual
scenario and estimating the impact of each on carbon fluxes at the study site.
RESULTS: The OBIA method performed well at almost all sites. Almost 500 km of
drains were detected within the peatland. In the error matrix method, overall
accuracy (OA) of detecting the drains was 94% and the kappa statistic was 0.66.
The OA for all sub-areas, except one, was 95-97%. The CCQ was 85%, 85% and 71%
respectively. The OBIA method was the most cost effective way to map peatland
drains and was at least 55% cheaper than either field survey or manual
digitisation, respectively. The extracted drain maps were used constrain the
study area CO2 flux which was 19% smaller than the prescribed Peatland Code value
for drained peatlands. CONCLUSIONS: The OBIA method used in this study showed
that it is possible to accurately extract maps of fine scale peatland drains over
large areas in a cost effective manner. The development of methods to map the
spatial extent of drains is important as they play a critical role in peatland
carbon dynamics. The objective of this study was to extract data on the spatial
extent of drains on a blanket bog in the west of Ireland. The results show that
information on drain extent and location can be extracted from high resolution
imagery and mapped with a high degree of accuracy. Under Article 3.4 of the Kyoto
Protocol Annex 1 parties can account for greenhouse gas emission by sources and
removals by sinks resulting from "wetlands drainage and rewetting". The ability
to map the spatial extent, density and location of peatlands drains means that
Annex 1 parties can develop strategies for drain blocking to aid reduction of CO2
emissions, DOC runoff and water discoloration. This paper highlights some
uncertainty around using one-size-fits-all emission factors for GHG in drained
peatlands and re-wetting scenarios. However, the OBIA method is robust and
accurate and could be used to assess the extent of drains in peatlands across the
globe aiding the refinement of peatland carbon dynamics .
PMID- 28413852
TI - Combining airborne laser scanning and Landsat data for statistical modeling of
soil carbon and tree biomass in Tanzanian Miombo woodlands.
AB - BACKGROUND: Soil carbon and biomass depletion can be used to identify and
quantify degraded soils, and by using remote sensing, there is potential to map
soil conditions over large areas. Landsat 8 Operational Land Imager satellite
data and airborne laser scanning data were evaluated separately and in
combination for modeling soil organic carbon, above ground tree biomass and below
ground tree biomass. The test site is situated in the Liwale district in
southeastern Tanzania and is dominated by Miombo woodlands. Tree data from 15 m
radius field-surveyed plots and samples of soil carbon down to a depth of 30 cm
were used as reference data for tree biomass and soil carbon estimations.
RESULTS: Cross-validated plot level error (RMSE) for predicting soil organic
carbon was 28% using only Landsat 8, 26% using laser only, and 23% for the
combination of the two. The plot level error for above ground tree biomass was
66% when using only Landsat 8, 50% for laser and 49% for the combination of
Landsat 8 and laser data. Results for below ground tree biomass were similar to
above ground biomass. Additionally it was found that an early dry season
satellite image was preferable for modelling biomass while images from later in
the dry season were better for modelling soil carbon. CONCLUSION: The results
show that laser data is superior to Landsat 8 when predicting both soil carbon
and biomass above and below ground in landscapes dominated by Miombo woodlands.
Furthermore, the combination of laser data and Landsat data were marginally
better than using laser data only.
PMID- 28413853
TI - Characterization of the gut microbiota in the golden takin (Budorcas taxicolor
bedfordi).
AB - The gut microbiota of mammals is a complex ecosystem, which is essential for
maintaining gut homeostasis and the host's health. The high throughput sequencing
allowed us to gain a deeper insight into the bacterial structure and diversity.
In order to improve the health status of the endangered golden takins, we first
characterized the fecal microbiota of healthy golden takins using high throughput
sequencing of the 16S rRNA genes V3-V4 hypervariable regions. Our results showed
that, Firstly, the gut microbiota community comprised 21 phyla, 40 classes, 62
orders, 96 families, and 216 genera. Firmicutes (67.59%) was the most abundant
phylum, followed by Bacteroidetes (23.57%) and Proteobacteria (2.37%). Secondly,
the golden takin maintained higher richness in spring than in the winter while
community diversity and evenness was not significantly different. Thirdly, four
female golden takins demonstrated highly similar microbiota and the five golden
takin males had relatively highly similar microbiota. All of our results might
indicate that the fecal microbiota of golden takins were influenced by the season
and the animal's sex. The findings provided theoretical basis regarding the gut
microbiota of golden takins and may offer new insights to protect this endangered
species.
PMID- 28413854
TI - Use of a pocket compression device for the prevention and treatment of pocket
hematoma after pacemaker and defibrillator implantation (STOP-HEMATOMA-I).
AB - BACKGROUND: Pocket hematoma is a recognized complication after placement of
cardiac implantable electronic devices and is associated with increased device
infection, length of hospitalization, and morbidity especially with uninterrupted
antiplatelet agents and anticoagulants. We assessed the use of a post-surgical
vest to decrease the incidence of pocket hematoma in patients undergoing device
implantation with uninterrupted antiplatelet and anticoagulants. METHODS: In this
observational study, a vest was used by 20 consecutive patients who were compared
to 20 age-, gender-, procedure-matched patients who received standard care. All
patients were continued on antiplatelet and anticoagulants in the perioperative
period. The pocket was assessed at post procedure day 0, 2, and 7, respectively.
RESULTS: There were no significant differences in the baseline characteristics
between both groups. Baseline mean international normalized ratio (INR) was
significantly higher in the vest group when compared with the control group (2.7
+/- 0.4 vs. 2.2 +/- 0.3 = <0.001). The incidence of pocket hematoma was
significantly lower in the vest group than the control group (0 vs 30%, p = 0.02)
at the end of 7 days. Control group had a total of six hematomas with one patient
requiring evacuation and blood transfusion. The vest group had three hematomas on
day 2 that resolved by day 7. CONCLUSIONS: The risk of moderate or large pocket
hematoma is significantly reduced with the use of this vest in high-risk patients
undergoing implantable devices on uninterrupted antiplatelet and anticoagulants.
PMID- 28413855
TI - Frequency of pacemaker malfunction associated with monopolar electrosurgery
during pulse generator replacement or upgrade surgery.
AB - PURPOSE: The aim of this study is to investigate the frequency of electrosurgery
related pacemaker malfunction. METHODS: A retrospective study was conducted to
investigate electrosurgery-related pacemaker malfunction in consecutive patients
undergoing pulse generator (PG) replacement or upgrade from two large hospitals
in Minneapolis, MN between January 2011 and January 2014. The occurrence of this
pacemaker malfunction was then studied by using MAUDE database for all four major
device vendors. RESULTS: A total of 1398 consecutive patients from 2 large
tertiary referral centers in Minneapolis, MN undergoing PG replacement or upgrade
surgery were retrospectively studied. Four patients (0.3% of all patients), all
with pacemakers from St Jude Medical (2.8%, 4 of 142) had output failure or
inappropriately low pacing rate below 30 bpm during electrosurgery, despite being
programmed in an asynchronous mode. During the same period, 1174 cases of
pacemaker malfunctions were reported on the same models in MAUDE database, 37 of
which (3.2%) were electrosurgery-related. Twenty-four cases (65%) had output
failure or inappropriate low pacing rate. The distribution of adverse events was
loss of pacing (59.5%), reversion to backup pacing (32.4%), inappropriate low
pacing rate (5.4%), and ventricular fibrillation (2.7%). The majority of these
(78.5%) occurred during PG replacement at ERI or upgrade surgery. No
electrosurgery-related malfunction was found in MAUDE database on 862 pacemaker
malfunction cases during the same period from other vendors. CONCLUSIONS:
Electrosurgery during PG replacement or upgrade surgery can trigger output
failure or inappropriate low pacing rate in certain models of modern pacemakers.
Cautions should be taken for pacemaker-dependent patients.
PMID- 28413856
TI - Erratum to: The Relationship Between Marijuana and Conventional Cigarette Smoking
Behavior from Early Adolescence to Adulthood.
PMID- 28413857
TI - A New Look at Genetic and Environmental Architecture on Lipids Using Non-Normal
Structural Equation Modeling in Male Twins: The NHLBI Twin Study.
AB - This study examined genetic and environmental influences on the lipid
concentrations of 1028 male twins using the novel univariate non-normal
structural equation modeling (nnSEM) ADCE and ACE models. In the best fitting
nnSEM ADCE model that was also better than the nnSEM ACE model, additive genetic
factors (A) explained 4%, dominant genetic factors (D) explained 17%, and common
(C) and unique (E) environmental factors explained 47% and 33% of the total
variance of high-density lipoprotein cholesterol (HDL-C). The percentage of
variation explained for other lipids was 0% (A), 30% (D), 34% (C) and 37% (E) for
low-density lipoprotein cholesterol (LDL-C); 30, 0, 31 and 39% for total
cholesterol; and 0, 31, 12 and 57% for triglycerides. It was concluded that
additive and dominant genetic factors simultaneously affected HDL-C
concentrations but not other lipids. Common and unique environmental factors
influenced concentrations of all lipids.
PMID- 28413858
TI - EPR Studies on the Properties of Model Photoreceptor Membranes Made of Natural
and Synthetic Lipids.
AB - The membranes of retina photoreceptors have unique lipid composition. They
contain a high concentration of polyunsaturated docosahexaenoic acid, with six
double bonds, and are enriched in phosphatidylethanolamines. Based on their
phospholipid composition and cholesterol content, membranes of photoreceptors can
be divided into three types: plasma membrane, young disks membranes, and old
disks membranes. High amount of docosahexaenoic acid, abundant illumination, and
high respiratory demands make these membranes sensitive to oxidative stress and
lipid peroxidation. Human retinas are not easily available for research,
therefore most research is done on bovine retinas. However, to follow, in a
controlled manner, the changes in membrane properties caused by different factors
it seems advisable to apply carefully prepared models of photoreceptor membranes.
Using synthetic lipids we prepared liposome models of three types of
photoreceptor membranes, and by means of electron paramagnetic resonance
spectroscopy and spin labeling technique we compared polarity and fluidity of
those model membranes with the properties of membranes consisting of natural
lipids extracted from photoreceptor outer segments of bovine retinas.
Additionally, we studied the effect of oxidation on the membrane properties in
the presence and in the absence of zeaxanthin, which is an antioxidant naturally
present in the human retina. The results show that there are significant
differences in polarity and fluidity between all investigated membranes, which
reflect differences in their lipid composition. The properties of the membranes
made of natural photoreceptor outer segment lipids are most similar to the ones
of the models of old disks membranes. Oxidation did not change the membrane
properties significantly; however, a slight ordering effect was observed in
liposomes made of natural photoreceptor outer segment lipids and in the model of
old disks membranes. Zeaxanthin affected polarity and fluidity mostly in the
model of old disks membranes. The results show that by careful selection and
appropriate proportions of lipid mixtures, it is possible to obtain synthetic
membranes of the properties similar to the natural ones.
PMID- 28413860
TI - Distribution and characterisation of CCK containing enteroendocrine cells of the
mouse small and large intestine.
AB - There is general consensus that enteroendocrine cells, EEC, containing the
enteric hormone cholecystokinin (CCK) are confined to the small intestine and
predominate in the duodenum and jejunum. Contrary to this, EEC that express the
gene for CCK have been isolated from the large intestine of the mouse and there
is evidence for EEC that contain CCK-like immunoreactivity in the mouse colon.
However, the human and rat colons do not contain CCK cells. In the current study,
we use immunohistochemistry to investigate CCK peptide presence in endocrine
cells, PCR to identify cck transcripts and chromatography to identify CCK peptide
forms in the mouse small and large intestine. The colocalisation of CCK and 5-HT,
hormones that have been hypothesised to derive from cells of different lineages,
was also investigated. CCK immunoreactivity was found in EEC throughout the mouse
small and large intestine but positive cells were rare in the rectum.
Immunoreactive EEC were as common in the caecum and proximal colon as they were
in the duodenum and jejunum. CCK gene transcripts were found in the mucosa
throughout the intestine but mRNA for gastrin, a hormone that can bind some anti
CCK antibodies, was only found in the stomach and duodenum. Characterisation of
CCK peptides of the colon by extraction, chromatographic separation and
radioimmunoassay revealed bioactive amidated and sulphated forms, including CCK-8
and CCK-33. Moreover, CCK-containing EEC in the large intestine bound antibodies
that target the biologically active sulfated form. Colocalisation of CCK and 5-HT
occurred in a proportion of EEC throughout the small intestine and in the caecum
but these hormones were not colocalised in the colon, where there was CCK and PYY
colocalisation. It is concluded that authentic, biologically active, CCK occurs
in EEC of the mouse large intestine.
PMID- 28413861
TI - Preconditioning with melatonin improves therapeutic outcomes of bone marrow
derived mesenchymal stem cells in targeting liver fibrosis induced by CCl4.
AB - Preconditioning of mesenchymal stem cells (MSCs) with melatonin (MT) has shown
promising results in animal models of myocardial infarction, renal ischemia and
cerebral ischemia. Here, we use this strategy in the liver fibrosis induced by
CCl4. There were five groups: normal, CCl4, CCl4 + vehicle, CCl4 + BMMSCs and
CCl4 + MT-bone marrow (BM)-derived MSCs (MT-BMMSCs). CCl4 was injected twice
weekly for 8 weeks and treatment either with cells or vehicle was performed at
the beginning of week 5 with a single dose. BMMSCs were preconditioned with MT
for 24 h before injection. MT-BMMSCs had a high ability of homing into the
injured liver (P <= 0.05 vs. BMMSCs). The CCl4 + MT-BMMSCs group showed higher
percentage of glycogen storage but lower percentage of collagen and lipid
accumulation (P <= 0.05 vs. CCl4 + BMMSCs). The CCl4 + MT-BMMSCs group showed
lower expressions of transforming growth factor-beta1 (TGF-beta1) and Bax and
lower content of sera alanine aminotransferase (ALT) but higher expressions of
matrix metalloproteinases (MMPs) and Bcl2 compared with the BMMSCs group (P <=
0.05). The results showed the better therapeutic outcomes of MT preconditioning
by probably improving cell homing and also better maintenance of the balance
between matrix degrading and accumulating factors.
PMID- 28413862
TI - A simple strategy for culturing morphologically-conserved rat hypothalamic
tanycytes.
AB - Hypothalamic tanycytes are specialized bipolar ependymal cells that line the
floor of the third ventricle. Given their strategic location, tanycytes are
believed to play several key functions including being a selective barrier and
controlling the amount of hypothalamic-derived factors reaching the anterior
pituitary. The in vitro culture of these cells has proved to be difficult. Here,
we report an improved method for the generation of primary cultures of rat
hypothalamic tanycytes. Ependymal cultures were derived from tissue dissected out
of the median eminence region of 10-day-old rats and cultured in a chemically
defined medium containing DMEM:F12, serum albumin, insulin, transferrin and the
antibiotic gentamycin. After 7 days in vitro, ~30% of the cultured cells
exhibited morphological features of tanycytes as observed by phase contrast or
scanning electron microscopy. Tanycyte-like cells were strongly immuno-reactive
for vimentin and dopamine-cAMP-regulated phospho-protein (DARPP-32) and weakly
immune-reactive for glial fibrillary acidic protein. Tanycyte-like cells
displayed a stable negative resting plasma membrane potential and failed to show
spiking properties in response to current injections. When exposed to fluorescent
beads in the culture medium, tanycyte-like cells exhibited a robust endocytosis.
Thus, the present method effectively yields cultures containing tanycyte-like
cells that resemble in vivo tanycytes in terms of morphologic features and
molecular markers as well as electrical and endocytic activity. To our knowledge,
this is the first protocol that allows the culturing of tanycyte-like cells that
can be individually identified and that conserve the morphology of tanycytes in
their natural physiological environment.
PMID- 28413859
TI - Meniscus, articular cartilage and nucleus pulposus: a comparative review of
cartilage-like tissues in anatomy, development and function.
AB - The degradation of cartilage in the human body is impacted by aging, disease,
genetic predisposition and continued insults resulting from daily activity. The
burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral
disc damage, knee replacement surgeries, etc.) is daunting in light of
substantial economic and social stresses. This review strives to broaden the
scope of regenerative medicine and tissue engineering approaches used for
cartilage repair by comparing and contrasting the anatomical and functional
nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many
review papers have provided detailed evaluations of these cartilages and
cartilage-like tissues individually but none have comprehensively examined the
parallels and inconsistencies in signaling, genetic expression and extracellular
matrix composition between tissues. For the first time, this review outlines the
importance of understanding these three tissues as unique entities, providing a
comparative analysis of anatomy, ultrastructure, biochemistry and function for
each tissue. This novel approach highlights the similarities and differences
between tissues, progressing research toward an understanding of what defines
each tissue as distinctive. The goal of this paper is to provide researchers with
the fundamental knowledge to correctly engineer the meniscus, AC and NP without
inadvertently developing the wrong tissue function or biochemistry.
PMID- 28413863
TI - Metabolism and homeostasis in the kidney: metabolic regulation through insulin
signaling in the kidney.
AB - Metabolic signaling pathways orchestrate the dynamic turnover between catabolic
and anabolic processes. Thereby, they ensure the viability of the cell and assure
proper function of the tissue in changing environments regarding the availability
of nutrients. Yet, renal cells are not considered to be prime targets of
metabolic signaling. Research of the last decade has proposed new roles of
specifically altered metabolic signaling pathways. In particular, the insulin
signaling cascade, a potent regulator of cellular metabolism and energy
homeostasis, seems to be implicated in the progression of diabetic and non
diabetic kidney disease. The aim of this review is to summarize the current
knowledge on metabolic signaling events in different renal compartments in states
of health and disease. We will focus on the role of insulin signaling events and
highlight recent advances in the understanding of the regulatory interplay
between insulin signaling and mitochondrial function contributing to the
pathogenesis of kidney disease.
PMID- 28413864
TI - Evaluation of Intracranial Microvessel Visualization in Mouse and Dog Models by
Using a New Rotating Cerium Anode X-ray System.
AB - OBJECTIVE: Lacunar stroke may be caused by infarction of small perforating
branches of the middle cerebral artery. We developed a microangiographic X-ray
system using a cerium anode to evaluate the perforating branches. METHODS: Iodine
has K-edges at 33.2 kilo electron volts. Cerium yields a characteristic X-ray of
34.6 kilo electron volts, therefore, the cerium anode X-ray system could detect
tiny amounts of contrast material. First, an X-ray chart was used to evaluate the
resolution. Second, the brains of mice were dissected and irradiated. Third, the
brains of dogs were excluded and irradiated. Fourth, iodine was perfused into the
carotid artery of living dogs during brain imaging. RESULTS: In the first
experiment, the cerium anode X-ray system elicited 4.86 clear line pairs. In
mice, the perforating branches of the middle cerebral artery could be visualized.
The perforating branches were clearly observed in dog brains ex situ even through
an acrylic plate, but not in conventional X-ray images. Iodine moving inside the
perforating branches was visualized in dog brains in situ using the cerium anode
X-ray system. CONCLUSION: The cerium anode X-ray system allowed us to visualize
the perforating branches of the middle cerebral artery in living dogs.
PMID- 28413865
TI - Protein-losing Enteropathy Caused by Spontaneous Reduction of Intussusception
with Meckel's Diverticulum.
AB - Protein-losing enteropathy (PLE) is a relatively rare condition. In this article,
we report the case of a 6-year-old boy diagnosed with PLE who developed
intussusception, in whom at operation Meckel's diverticulum was identified in his
intestine. Spontaneous reduction of intussusception is thought to relate to the
mechanism of PLE.
PMID- 28413866
TI - Inositol Hexakisphosphate Kinase 2 is a Presymptomatic Biomarker for Amyotrophic
Lateral Sclerosis.
AB - OBJECTIVE: Inositol hexakisphosphate kinase 2 (InsP6K2), an enzyme that converts
inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7),
induces cell death. InsP6K2 is abundant in the central nervous system, especially
anterior horn cells of spinal cord. To identify the role of InsP6K2 in
amyotrophic lateral sclerosis (ALS), we investigated the expression levels of
InsP6K2 in transgenic mice expressing mutant superoxide dismutase-1 (SOD1) (mSOD1
Tg mice). METHODS: The specimens of spinal cords were obtained from mSOD1 Tg mice
and age-matched wild-type mice. We investigated the expression of InsP6K2 at the
gene and protein levels of the spinal cord in mSOD1 Tg and wild-type mice.
RESULTS: The gene expression levels of InsP6K2 in mSOD1 Tg mice was significantly
higher than that in wild-type mice before ALS symptoms developed. In
immunohistochemistry and western blotting results showed that InsP6K2
translocated from the nucleus to the cytoplasm in mSOD1 Tg mice. CONCLUSION:
These findings suggest that InsP6K2 activates in mSOD1 Tg mice before the onset
of ALS. Therefore, InsP6K2 might be a presymptomatic biomarker for ALS.
PMID- 28413867
TI - A Study of Adjuvant Chemoradiotherapy with Tri-weekly Cisplatin for Postoperative
High-risk Oral Squamous Cell Carcinoma.
AB - OBJECTIVE: The aim of this study was to assess the feasibility and safety profile
of concurrent chemoradiotherapy with cisplatin in Japanese patients with
postoperative high-risk oral cancer. METHODS: Patients with high-risk
pathological features were selected from patients with oral squamous cell
carcinoma who underwent surgery at the Department of Oral and Maxillofacial
Surgery, Tokai University Hospital. Patients were given adjuvant
chemoradiotherapy with tri-weekly cisplatin (100 mg/m2) (66 Gy/33 Fr), and the
treatment completion rate was examined. RESULTS: A total of 27 patients were
enrolled between April 2011 and December 2012, including 19 males and 8 females.
The median follow-up period was 36 months, and the protocol completion rate was
81.5%. Grade 3 or higher adverse events included leukopenia in 16 patients
(59.3%), anemia in 7 patients (25.9%), mucositis in 2 patients (7.4%), increased
creatinine in 1 patient (3.7%), nausea in 4 patients (14.8%), and anorexia in 12
patients (44.4%). The 3-year overall survival rate was 66.7%, relapse-free
survival rate was 63.0%, and locoregional control rate was 77.8%. CONCLUSION: The
feasibility and safety profile of concurrent chemoradiotherapy with cisplatin in
Japanese patients with postoperative high-risk oral cancer were comparable to
pivotal phase III trials.
PMID- 28413868
TI - Goniosynechialysis and Repositioning of Intraocular Lens in a Case of Secondary
Angle Closure Glaucoma.
AB - PURPOSE: Implanting intraocular lens (IOL) in proper direction is important in
cataract surgery to reduce the possibility of undesirable complications. We
experienced a case who underwent vitrectomy combined with cataract surgery and
developed secondary angle closure glaucoma caused by IOL misdirection.
Goniosynechialysis (GSL) and repositioning of IOL successfully ameliorated the
high intraocular pressure (IOP). CASE REPORT: A 64-year-old male with massive
vitreous hemorrhage underwent vitrectomy combined with cataract surgery. In
implanting IOL, posterior capsule was accidentally raptured, and we were obliged
to implant IOL reversely in the ciliary sulcus. A month postoperatively, the
capture of IOL by iris and the shallow anterior chamber with iris bombe formation
led to the elevated IOP up to 60 mmHg. Laser iridotomy and maximum anti-glaucoma
medications including oral carbon anhydrase inhibitor could not control IOP.
Subsequently, we performed GSL and IOL repositioning to correct the lens
direction and the IOP was successfully reduced to normal level. CONCLUSION:
Reversely sulcus-implanted IOL should be repositioned to prevent secondary angle
closure glaucoma.
PMID- 28413869
TI - Salivary Duct Carcinoma with Invasive Micropapillary and Rhabdoid Feature Arising
in the Submandibular Gland.
AB - Salivary duct carcinoma (SDC) is a high-grade malignant salivary gland tumor
associated with poor prognosis, frequent recurrence, and metastasis. An 82-year
old man presented at the department of oral and maxillofacial surgery at Tokai
University Hospital with a painless swelling in the right submandibular region
that had been there for 20 years. On presentation, an elastic hard tumor, 50 * 50
mm in size, was observed in the submandibular region. Diagnostic imaging was
performed, and a malignant tumor in the submandibular gland was suspected. The
suspected tumor was excised and postoperative radiotherapy and adjuvant
chemotherapy were performed. Despite this treatment, the patient died of multiple
metastases 12 months postoperatively. SDCs are often diagnosed as carcinoma ex
pleomorphic adenomas and multiple variants and subtypes exist. This case was
histopathologically rare in terms of the coexistence of invasive micropapillary
and rhabdoid features.
PMID- 28413870
TI - Performance Evaluation of a Newly Developed and Fully Automated Bacteriological
Analyzer "RAISUS ANY" for Antimicrobial Susceptibility Testing of Fastidious
Bacteria Haemophilus influenzae and Streptococcus pneumoniae.
AB - OBJECTIVE: Antimicrobial susceptibility testing for fastidious bacteria, such as
Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S.
pneumoniae) has been performed manually. We evaluated the performance of a newly
developed fully automated system for rapid bacterial identification and
antimicrobial susceptibility testing "RAISUS ANY" (Nissui Pharmaceutical Co.,
Ltd.). METHODS: We evaluated the performance of "RAISUS ANY" for measurement of
minimal inhibitory concentrations (MICs) of H. influenzae and S. pneumoniae, in
comparison with the manual method (DP34, Eiken Chem. Co., Ltd.). The
repeatability of MICs was studied using the reference strain of these bacteria,
obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA).
RESULTS: The comparison with the manual method for 35 and 36 clinical strains of
H. influenzae and S. pneumonia showed 62.9-100% and 86.1-100% agreement,
respectively. Five of 35 H. influenzae strains that showed a trailing effect were
stably and accurately measured for MICs without a variation among the examiners.
CONCLUSION: In conclusion, the automated system "RAISUS ANY" provided a reliable
MICs data for H. influenzae and S. pneumonia, suggesting its improvement in
performance and reliability for routine antimicrobial susceptibility testing in
clinical bacteriological laboratories.
PMID- 28413871
TI - Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells
between Humans and a Humanized Xenograft Model.
AB - The aim of this study is to evaluate the feasibility of NOD/Shi-scid
IL2Rgammanull(NOG) mice transplanted with human CD34+/CD38-/Lin-/low
hematopoietic cells from cord blood (CB) as an experimental model of the gene
expression in human hematopoiesis. We compared the gene expressions of human
CD34+/CD38-/Lin-/low cells from human bone marrow (BM) and in xenograft models.
The microarray data revealed that 25 KEGG pathways were extracted from the
comparison of human CD34+/CD38-/Lin-/low HSCs between CB and BM, and that 17 of
them--which were mostly related to cellular survival, RNA metabolism and lymphoid
development--were shared with the xenograft model. When the probes that were
commonly altered in CD34+/CD38-/Lin-/low cells from both human and xenograft BM
were analyzed, most of them, including the genes related hypoxia, hematopoietic
differentiation, epigenetic modification, translation initiation, and RNA
degradation, were downregulated. These alterations of gene expression suggest a
reduced differentiation capacity and likely include key alterations of gene
expression for settlement of CB CD34+/CD38-/Lin-/low cells in BM. Our findings
demonstrate that the xenograft model of human CB CD34+/CD38-/Lin-/low cells using
NOG mice was useful, at least in part, for the evaluation of the gene expression
profile of human hematopoietic stem cells.
PMID- 28413872
TI - Favorable Effect on Blood Volume Control in Hemodialysis Patients with Type 2
Diabetes after Switching from Insulin Therapy to Liraglutide, a Human Glucagon
like Peptide-1 Analog--Results from a Pilot Study in Japan-.
AB - OBJECTIVE: Hemodialysis patients are advised to limit the intake of foods in
order to control volume status and body weight (BW). We report the clinical
course of five Japanese hemodialysis patients with type 2 diabetes mellitus
(T2DM) who were switched from insulin to liraglutide, and the efficacy of the
treatment, especially in terms of changes in interdialysis weight gain (IDWG).
METHODS: This retrospective pilot study included 5 Japanese hemodialysis patients
with T2DM. Insulin and other oral hypoglycemic agents, if any, were discontinued
before switching to liraglutide. The initial dose of liraglutide was set at 0.3
mg/day for more than 1 week, increased to 0.6 mg/day for more than 1 week and
then, to 0.9 mg/day if needed. RESULTS: At baseline, the mean body mass index
(BMI) was 23.2 +/- 1.2 kg/m2 and mean IDWG was 2.0 +/- 0.4 kg. The required dose
of liraglutide ranged from 0.3 to 0.9 mg/day. At the end of 3-month treatment,
liraglutide reduced HbA1c level, BMI, and IDWG. A significant decrease in
cardiothoracic ratio was confirmed on chest radiography. CONCLUSION: Switching
from insulin to liraglutide seems effective in hemodialysis patients with T2DM,
especially in those with difficult blood fluid volume control associated with
failure of dietary restriction.
PMID- 28413874
TI - Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR
AC): summary of conclusions and recommendations, 1-2 February 2017 meeting.
PMID- 28413873
TI - The Apparent Diffusion Coefficient (ADC) as a Potential Marker of Inflammation
Associated with Body Abscesses.
AB - OBJECTIVE: To assess the feasibility of apparent diffusion coefficient analysis
in evaluating the inflammatory severity of extracranial abscesses. METHODS: This
retrospective study included 23 patients with solitary body abscesses (except
those in the brain) who underwent 1.5-T diffusion-weighted magnetic resonance
imaging (DWI) at b-values of 0 and 1000 s/mm2. Three types of the Apparent
Diffusion Coefficient (ADC) measurements of abscesses were performed: the mean
ADC value in region of interest (ROI), volume of interest (VOI), and histogram
analysis of the ADC distribution in the VOI. Furthermore, two different areas
were used: high-intensity area on b = 0 and b = 1000 s/mm2 images. Subsequently,
correlations between ADC data and C-reactive protein (CRP) levels were assessed
using Pearson's correlation coefficient (R) analyses. RESULTS: The strongest
correlation was observed between the mean ADC value in VOI and CRP level (R =
0.78, P < 0.01), followed by ROI (R = 0.77, P < 0.01) by using the high-intensity
area on the b = 0 s/mm2 images. CONCLUSION: The mean ADC value in the ROI
encompassing the abscess at a b-value of 0 s/mm2 may be useful to assess the
inflammatory activity of an abscess in daily practice.
PMID- 28413875
TI - Zika virus: an epidemiological update.
PMID- 28413876
TI - Generation of an Orthogonal Protein-Protein Interface with a Noncanonical Amino
Acid.
AB - We have engineered the protein interface of the Escherichia coli chorismate
mutase (EcCM) homodimer to be dependent on incorporation of a noncanonical amino
acid (ncAA) at residue 72. The large hydrophobic amino acid p-benzoyl
phenylalanine (pBzF) was substituted for Tyr72, which led to a catalytically
inactive protein. A library of five residues (Leu25', Arg29', Leu76, Ile80' and
Asp83') surrounding pBzF72 was generated and subjected to a growth based
selection in a chorismate mutase deficient strain. An EcCM variant (Phe25',
pBzF72, Thr76, Gly80' and Tyr83') forms a stable homodimer, has catalytic
activity similar to the wild type enzyme, and unfolds with a Tm of 53 degrees C.
The X-ray crystal structure reveals a pi-pi stacking and hydrogen bonding
interactions that stabilize the new protein interface. The strategy described
here should be useful for generating organisms that are dependent on the presence
of a ncAA for growth.
PMID- 28413877
TI - Correction to Reduction Sensitive Lipid Conjugates of Tenofovir: Synthesis,
Stability, and Antiviral Activity.
PMID- 28413878
TI - An Efficient Method Based on Lattice Construction and the Genetic Algorithm for
Optimization of Large Lennard-Jones Clusters.
AB - Geometric methods for the construction of three structural motifs, the
icosahedron, Ino's decahedron, and the complete octahedron, are proposed. On the
basis of the constructed lattices and the genetic algorithm, a method for
optimization of large size Lennard-Jones (LJ) clusters is presented. Initially,
the proposed method is validated by optimization of LJ13-309 clusters with the
above structural motifs. Results show that the proposed method successfully
located all the lowest known minima with an excellent performance; for example,
based on Ino's decahedron with 147 lattice sites, the mean time consumed for
successful optimization of LJ75 is only 0.61 s (Pentium III, 1 GHz), and the
percentage success is 100%. Then, putative global minima of LJ310-561 clusters
are predicted with the method. By theoretical analysis, these global minima are
reasonable, although further verification or proof is still needed.
PMID- 28413879
TI - Structural Distribution of Lennard-Jones Clusters Containing 562 to 1000 Atoms.
AB - On the basis of the icosahedral and decahedral lattices, the lowest energies of
the Lennard-Jones (LJ) clusters containing 562-1000 atoms with the two motifs are
obtained by using a greedy search method (GSM). Energy comparison between the
decahedra and icosahedra shows that icosahedral structures are predominant.
However, most of the icosahedral structures with the central vacancy are more
stable than that without the central vacancy. On the other hand, in the range of
562-1000 atoms, there are 41 LJ clusters with the decahedral motif. The number of
decahedra increases remarkably compared with the smaller LJ clusters.
Consequently, the magic numbers and growth characters of decahedral clusters are
also studied, and the results show that the magic numbers of intermediate
decahedral clusters occur at 654, 755, 807, 843, 879, 915, and 935.
PMID- 28413880
TI - Syntheses of Gliocladin C and Related Alkaloids.
AB - A unique approach to gliocladin C and related alkaloids was developed that
features an unprecedented nucleophilic addition of a diketopiperazine to an
isatin derivative followed by a Friedel-Crafts alkylation of the resultant
tertiary alcohol with indole to set the key quaternary center. Chemoselective
oxindole reduction and cyclization delivered a pivotal hexahydropyrrolo[2,3
b]indole diketopiperazine intermediate that was readily converted into (+/-)
gliocladin C, (+/-)-T988C, and (+/-)-gliocladine C, culminating in the shortest
approach to these alkaloids reported to date.
PMID- 28413881
TI - Molecular Mechanism of Stabilizing the Helical Structure of Huntingtin N17 in a
Micellar Environment.
AB - Huntington's disease is a deadly neurodegenerative disease caused by the
fibrilization of huntingtin (HTT) exon-1 protein mutants. Despite extensive
efforts over the past decade, much remains unknown about the structures of
(mutant) HTT exon-1 and their enigmatic roles in aggregation. Particularly,
whether the first 17 residues in the N-terminal (HTT-N17) adopt a helical or a
coiled structure remains unclear. Here, with the rigorous study of molecular
dynamics simulations, we explored the most possible structures of HTT-N17 in both
dodecylphosphocholine (DPC) micelles and aqueous solution, using three commonly
applied force fields (OPLS-AA/L, CHARMM36, and AMBER99sb*-ILDNP) to examine the
underlying molecular mechanisms and rule out potential artifacts. We show that
local environments are essential for determining the secondary structure of HTT
N17. This is evidenced by the insertion of five hydrophobic residues of HTT-N17
into the DPC micelle, which promotes the formation of an amphipathic helix,
whereas such amphipathic helices unfold quickly in aqueous solution. A relatively
low free-energy barrier (~3 kcal/mol) for the secondary structure transformation
was also observed for all three force fields from their respective folding-free
energy landscapes, which accounts for possible HTT-N17 conformational changes
upon environmental shifts such as membrane binding and protein complex
aggregation.
PMID- 28413882
TI - Consequences of Surface Oxophilicity of Ni, Ni-Co, and Co Clusters on Methane
Activation.
AB - This study describes a new C-H bond activation pathway during CH4-CO2 reactions
on oxophilic Ni-Co and Co clusters, unlike those established previously on Ni
clusters. The initial C-H bond activation remains as the sole kinetically
relevant step on Ni-Co, Ni, and Co clusters, but their specific reaction paths
vary. On Ni clusters, C-H bond activation occurs via an oxidative addition step
that involves a three-center (H3C...*...H)? transition state, during which a Ni
atom inserts into the C-H bond and donates its electron density into the C-H
bond's antibonding orbital. Ni-Co clusters are more oxophilic than Ni; thus,
their surfaces are covered with oxygen adatoms. An oxygen adatom and a vicinal Co
atom form a metal-oxygen site-pair that cleaves the C-H bond via a sigma bond
metathesis reaction, during which the Co inserts into the C-H bond while the
oxygen abstracts the leaving H-atom in a concerted, four-center
(H3C...*...H...O*)? transition state. Similarly, Co clusters also catalyze the
sigma bond metathesis step, but much less effectively because of their higher
oxophilicities, much stronger binding to oxygen, and less effective hydrogen
abstraction than Ni-Co clusters. On Ni-Co and Co clusters, the pseudo-first-order
rate coefficients are single-valued functions of the CO2-to-CO ratio (or H2O-to
H2 ratio), because this ratio prescribes the oxygen chemical potentials and the
relative abundances of metal-oxygen site-pairs through the water-gas shift
equilibrium. The direct involvement of reactive oxygen in the kinetically
relevant step leads to more effective CH4 turnovers and complete elimination of
coke deposition on Ni-Co bimetallic clusters.
PMID- 28413883
TI - Comment: The Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological
Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.
PMID- 28413884
TI - Incidence and Risk Factors of Venous Thromboembolism After Orthopaedic Foot and
Ankle Surgery.
AB - BACKGROUND: This study examines the incidence and risk of postoperative
symptomatic venous thromboembolism (VTE) after orthopaedic foot/ankle surgery.
MATERIALS: Patients that received foot/ankle surgery between 2006 and 2016 were
reviewed. Inclusion criteria were surgical patients that were without
coagulopathy, previous VTE, and/or using anticoagulation medications including
aspirin. Age, sex, body mass index, medical comorbidities, and surgical diagnosis
and procedure(s) were noted. Records were reviewed to see who developed a
symptomatic VTE within 90 days from surgery. RESULTS: This study involved 2774
patients that received foot/ankle surgery between 2006 and 2016. Of them, 22
(0.79%) developed a VTE within 90 days from surgery. The mean age of these
patients was 49.5 years. Twelve patients were male and 10 were female. Sixteen
patients were obese and 6 were nonobese. Postoperative VTEs were 14
infrapopliteal deep vein thrombosis (DVT), 1 suprapopliteal DVT, and 7 pulmonary
emboli. The most common surgeries involved were ankle fracture repair in 8
(0.29%), Achilles tendon repair in 2 (0.07%), ankle ligament reconstruction in 2,
and hammer-toe correction in 2 patients. Obesity was predictive of a
postoperative VTE to a statistically significant degree (P = .04). Age, sex,
medical comorbidities, diagnosis, and type of surgery were not significantly
prognostic for a postsurgical VTE (P >= .05). DISCUSSION: The incidence of VTE
after foot/ankle surgery is low. However, obese patients are at significantly
higher risk for VTE after such procedures. CLINICAL RELEVANCE: These findings are
important when educating patients as to their risks of developing a VTE after
orthopaedic foot/ankle surgery. LEVELS OF EVIDENCE: Level III: Retrospective
cohort study.
PMID- 28413885
TI - Understanding Latino Grandparents Raising Grandchildren Through a Bioecological
Lens.
AB - The purpose of this article is to provide a summary of the published research
addressing the challenges and strengths of Latino grandparents raising
grandchildren in the United States. Using the bioecological framework as a guide
to organize and understand the published literature addressing Latino grandparent
caregivers, we examined refereed articles published over the past 19 years. This
framework provides a lens for understanding and situating research on Latino
grandparents raising grandchildren to discover Latino grandparents' strengths and
challenges. The areas of foci include financial challenges, intergenerational
relationships, reasons for caregiving, health status, language barriers, and
culture. This article concludes with future research opportunities and a call to
action for more research on Latino grandparents raising grandchildren.
PMID- 28413886
TI - Effects of cadmium on Bcl-2/ Bax expression ratio in rat cortex brain and
hippocampus.
AB - To investigate the underlying mechanism of neurotoxicity of cadmium, we examined
the effects of intraperitoneal injection of cadmium on messenger RNA (mRNA)
expression of Bcl-2 (B-cell lymphoma 2) and Bax (Bcl2-associated x) genes and
caspase-3/7 activation in rat hippocampus and frontal cortex. Twenty-eight male
Wistar rats weighing 200-250 g were randomly divided into four groups. Control
group received saline and three other groups received cadmium at doses of 1, 2
and 4 mg/kg (body weight) for 15 successive days. One day after the last
injection, the hippocampus and frontal cortex were dissected and removed and then
the expression of Bcl-2 and Bax genes was evaluated using real-time polymerase
chain reaction and apoptotic studies was done using caspase-3/7 activation assay.
Cadmium reduced the mRNA level of Bcl-2 in the control group at doses of 1 ( p <
0.01), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus and cortex cells. The mRNA
level of Bax increased significantly compared to the control group at the doses
of 1 ( p < 0.05), 2 and 4 mg/kg ( p < 0.001) in rat hippocampus. The mRNA level
of Bax was increased significantly compared to the control group at the doses of
2 and 4 mg/kg ( p < 0.001) in rat cortex cells. Cadmium increased caspase-3/7
activity at doses of 1, 2 and 4 mg/kg in rat hippocampus. Caspase-3/7 activity
was increased significantly at dose of 4 mg/kg in rat cortex. This decreased Bcl
2/Bax mRNA ratio induces cell apoptosis. Apoptotic effect of cadmium may be
through the mitochondrial pathway by the activation of caspase-3/7.
PMID- 28413887
TI - Decline in sperm count in European men during the past 50 years.
AB - PURPOSE: To investigate whether the sperm concentration of European men is
deteriorating over the past 50 years of time. MATERIALS AND METHODS: We analysed
the data published in English language articles in the past 50 years in altering
sperm concentration in European men. RESULTS: A time-dependent decline of sperm
concentration ( r = -0.307, p = 0.02) in the last 50 years and an overall 32.5%
decrease in mean sperm concentration was noted. CONCLUSION: This comprehensive,
evidence-based meta-analysis concisely presents the evidence of decreased sperm
concentration in European male over the past 50 years to serve the scientific
research zone related to male reproductive health.
PMID- 28413888
TI - Implementation and evaluation of a Danish test battery for auditory processing
disorder in children.
AB - OBJECTIVE: This study presents a Danish test battery for auditory processing
disorder (APD). The tests were evaluated as to normative cut-off values (pass
fail criteria) and their test-retest reliability. DESIGN: The battery consists of
four behavioural tests: the filtered words (FW) test, the dichotic digits (DD)
test, the gap detection (GD) test and the binaural masking level difference
(BMLD) test. The tests were evaluated through listening experiments on children
with no known history of auditory problems. STUDY SAMPLE: The normative cut-off
values were obtained from 158 children (75 boys and 83 girls, aged 6-16 years),
whereas the test-retest reliability was obtained from 20 children (10 boys and 10
girls, aged 6-11 years). RESULTS: For each of the four tests one to four
different cut-off values were determined depending on whether the scores from the
two ears and the different age groups could be pooled. For each of the four tests
the test-retest reliability was found to be satisfactory. The test-retest
reliability was highest for the FW and the DD test. CONCLUSIONS: A Danish APD
test battery is now available for clinical use with normative data.
PMID- 28413889
TI - Shedding light into the black box: A prospective longitudinal study identifying
the CanMEDS roles of final year medical students' on-ward activities.
AB - INTRODUCTION: To our best knowledge, a rigorous prospective analysis of final
year medical students' (FY medical students) activity profiles during workplace
learning is lacking. The present study investigated the CanMEDS characteristics
of all on-ward activities performed by internal medicine FY medical students. We
tested the hypotheses that during FY medical student workplace training (I)
routine activities are predominantly performed, while supervised, more complex
activities are underrepresented with (II) FY medical students performing an
insufficient number of autonomous activities and that (III) the CanMEDS roles of
the Communicator and the Professional prevail. METHODS: During the second and the
sixth week of their final year trimester at the University of Heidelberg Medical
Hospital, N = 34 FY medical students (73% female; mean age 26.4 +/- 2.4) were
asked to keep a detailed record of all their on-ward activities and to document
the duration, mode of action (active versus passive; independent versus
supervised), estimated relevance for later practice, and difficulty-level in
specially designed activity logbooks. CanMEDS roles were assigned to the
documented activities via post-hoc expert consensus. RESULTS: About 4308
activities lasting a total of 2211.4 h were documented. Drawing blood (20.8%) was
the most frequently documented medical activity followed by full admission
procedures (9.6%). About 14.9% of the time was spent with non-medical activities.
About 82.1% of all medical activities performed went unsupervised. The
Communicator (42%), the Professional (38%), and the Collaborator (7%) were
assigned as the top three CanMEDS roles. CONCLUSIONS: The results call for
increased efforts in creating more authentic learning experiences for FY medical
students shifting towards more complex, supervised tasks, and improved team
integration.
PMID- 28413890
TI - Design, synthesis, and evaluation of novel 2-phenylpropionic acid derivatives as
dual COX inhibitory-antibacterial agents.
PMID- 28413891
TI - Safety of peripherally inserted central catheters during pregnancy: a
retrospective study.
AB - PURPOSE: We investigated the incidence of complications associated with
peripherally inserted central line catheters, inserted using a standardized
technique, during pregnancy and the postpartum period. MATERIALS AND METHODS: A
retrospective case series was performed that included all pregnant and postpartum
women who received peripherally inserted central catheters (PICCs) at a single
institution between 2006 and 2014. Patient demographics and data on infectious,
mechanical and thrombotic complications were collected. Some patients required
more than one line insertion during the same pregnancy. In these instances, only
the first line placement for each subject was included in the analysis of
complications. RESULTS: One hundred and forty-six catheters were inserted in 112
pregnant and postpartum patients. The total incidence of complications was 17%
(19/112). Specific complications included infection (n = 4, 3.6%), mechanical (n
= 5, 4.4%), deep venous thrombosis (n = 2, 1.8%) and other (n = 8, 7.1%).
Demographics of the complication and no complication groups were similar.
CONCLUSIONS: In contrast with previous studies, we report a complication rate
associated with peripheral line use in pregnant and postpartum women that appears
similar to that in non-pregnant populations.
PMID- 28413892
TI - Amyloid detection in the transverse carpal ligament of patients with hereditary
ATTR V30M amyloidosis and carpal tunnel syndrome.
AB - INTRODUCTION: Carpal tunnel syndrome (CTS) is a nonspecific manifestation of
hereditary ATTR amyloidosis (ATTRm). Amyloid deposition of wild-type TTR (WT
ATTR) has been found in transverse carpal ligament (TCL) in idiopathic CTS. We
retrospectively studied a group of patients with ATTRm and CTS submitted to
carpal tunnel release surgery (CTRS). METHODS: From the nerve conduction studies
performed in our Clinical Unit dedicated to hereditary amyloidosis between July
2009 and October 2013, we selected patients who fulfilled neurophysiological
criteria for CTS, had been submitted to CTRS and whose TCL was available for
pathology. Clinical registries were reviewed and amyloid detection in the
ligaments was performed using Congo-red staining. RESULTS: We included 16
patients: three males (18.8%), mean age = 46.1 years old, all with V30M mutation.
At the time of surgery, four patients were considered asymptomatic and 12
symptomatic carriers, five of them late-onset ATTRm (onset age >50 years old). In
all but one patient, the CTS preceded the polyneuropathy. Amyloid detection in
the TCL was positive in 14 patients (87.5%). DISCUSSION/CONCLUSIONS: In most
patients, CTS preceded or was contemporary to the polyneuropathy and amyloid
detection in TCL was positive. The detection of amyloid in TCL may add
specificity to CTS as an early manifestation of the disease but more studies are
needed.
PMID- 28413893
TI - The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin
Cutoff Points in Double Heterozygous Hb E/- -SEA alpha-Thalassemia-1 Carriers are
Dependent on Hemoglobin Levels.
AB - Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- -SEA (Southeast
Asian) (alpha-thalassemia-1) (alpha-thal-1) in patients first diagnosed as
carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular
volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed
in this double heterozygosity. However, the cutoff points of these parameters
have never been systematically established. Here, we analyzed Hb E and red blood
cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of
- -SEA and -alpha3.7 (alpha-thal-2; rightward) deletions, to establish the cutoff
points. Then, the established cutoff points were evaluated in 184 Hb E patients.
It was found that the cutoff points of Hb E, MCV, MCH were significantly
dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff
points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and
were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0
11.9 g/dL. Finally, in the group having Hb levels >=12.0 g/dL, the cutoff points
of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to
screen for the double heterozygous Hb E/- -SEA anomaly in patients initially
diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing
the suitable cutoff points of these three parameters.
PMID- 28413894
TI - Isolated Gastrocnemius Recession for the Treatment of Achilles Tendinopathy.
AB - BACKGROUND: Various treatment modalities have been described for Achilles
tendinopathy with varying degrees of success. The rationale for the gastrocnemius
recession procedure is to decrease the mechanical overload of the Achilles tendon
arising from an equinus contracture. METHODS: We retrospectively reviewed 25
patients who underwent an isolated gastrocnemius recession procedure at our
institution between May 2013 and April 2015 by a single surgeon. Clinical outcome
was evaluated on the basis of pain, utilizing visual analog scale (VAS) scores
and the Foot Function Index (FFI) by telephonic interview. Student's t test and
one-way analysis of variance were used for statistical analysis. RESULTS: The
average age of patients was 53.2 years with an average body mass index of 35.8
kg/m2. The average follow-up was 13.1 months. All 25 patients had a decrease in
VAS scores from an average of 8.9 preoperatively to 2.0 at the 6-week visit. The
average FFI went from 73.5 preoperatively to 27.4 at final follow-up. Two out of
25 patients had a postoperative sural neuritis with a total complication rate of
12%. Twenty-one of 25 patients (84%) reported total or significant pain relief.
CONCLUSION: The medium-term results of our study suggest that an isolated
gastrocnemius recession is a simple, effective, and safe surgical procedure for
the treatment of Achilles tendinopathy. LEVELS OF EVIDENCE: Therapeutic, Level
IV: Retrospective.
PMID- 28413895
TI - Response to restrictive lung disease: low EPAP - good ventilation. Is it real?
PMID- 28413896
TI - Congenital malformations, palliative care and postnatal redirection to more
intensive treatment - a review at a Swiss tertiary center.
AB - PURPOSE: The so-called lethal malformations pose ethical challenges. Most
affected fetuses die before or at birth. Live-born neonates commonly receive
palliative care. If the postnatal course is better than expected, redirection
towards more treatment may occur. We aimed to analyze this in a Swiss patient
cohort. MATERIALS AND METHODS: Over 6 years, fetal malformation was suspected in
1113 cases. We identified patients prenatally assigned to palliative care,
assessed pre- and postnatal diagnoses, and outcomes. RESULTS: Fourteen neonates
received palliative care. Eleven patients received palliative care following late
termination of pregnancy, for three, palliative care was planned and the fetus
died during delivery, for two, the outcome was unknown (incomplete
documentation). Genetic testing was performed in 50%. The predominant diagnostic
group was central nervous system malformations (33%), followed by chromosomal
aberrations (20%) and renal anomalies (17%). One child assigned to palliative
care was resuscitated. Antenatal findings were anhydramnios and pulmonary
hypoplasia. Postnatally, respiration was better than expected. The neonate was
admitted to intensive care, died on day one. CONCLUSIONS: Nervous system
malformations seem to be a major criterion for foregoing life-sustaining
interventions. Redirection towards more treatment is rare. This may reflect
precise prenatal prognostication; a degree of self-fulfilling prophecy cannot be
excluded.
PMID- 28413897
TI - Fibroadenoma With Pleomorphic Stromal Giant Cells: It's Not as Bad as It Looks!
AB - Clinically relevant histological categorization of fibroepithelial lesions can be
a daunting task, especially in a core needle biopsy. Assessment of stromal
nuclear atypia, including nuclear pleomorphism and mitotic activity, is a key
morphological feature employed to classify fibroepithelial lesions. We describe a
case of fibroadenoma with markedly atypical nuclear features in the stromal cells
that led to misclassification as phyllodes tumor in the core needle biopsy.
Excision showed a fibroadenoma containing pleomorphic stromal giant cells, with
occasional mitotic figures, including atypical forms. Aforementioned nuclear
findings in a fibroepithelial lesion raise a legitimate question of phyllodes
tumor. Knowledge of this pitfall may help avoid overtreatment of an otherwise
benign fibroepithelial lesion.
PMID- 28413898
TI - ERP correlates of attentional processing in spider fear: evidence of threat
specific hypervigilance.
AB - Attentional bias towards threat can be demonstrated by enhanced processing of
threat-related targets and/or greater interference when threat-related
distractors are present. These effects are argued to reflect processing within
the orienting and executive control networks of the brain respectively. This
study investigated behavioural (RT) and electrophysiological correlates of early
selective attention and top-down attentional control among females with high (n =
16) or low (n = 16) spider fear (Mean age = 22 years). Participants completed a
novel flanker go/nogo task in which a central schematic flower or spider stimulus
was flanked by either congruent or incongruent distractors. Participants
responded to green stimuli (go trials) and withheld response to yellow stimuli
(nogo trials). High fear participants demonstrated significantly shorter reaction
times and greater P1 amplitude to spider targets, suggesting specific
hypervigilance towards threat-relevant stimuli. In contrast to predictions, there
was little evidence for behavioural interference effects or differences in N2
amplitude when distractor stimuli were threat-relevant.
PMID- 28413899
TI - Changes in the oxidative stress/anti-oxidant system after exposure to sulfur
mustard and antioxidant strategies in the therapy, a review.
AB - Sulfur mustard, in a chemical name bis(2-chloroethyl) sulfide, is a chemical
warfare agent. It is cytotoxic and blister forming once spread over the skin.
Though exact molecular mechanism of sulfur mustard toxic action remains unknown,
inflammation and oxidative stress development are considered as the most relevant
pathological consequences. Applications of either low-molecular weight
antioxidants or cofactors for enzymatic antioxidants are considered as suitable
ways how to ameliorate the poisoning. In this article, survey of literature on
countermeasures against sulfur mustard poisoning are given and evidence of
oxidative stress role during sulfur mustard poisoning and availability of
antioxidants for the therapy are discussed.
PMID- 28413900
TI - Efficacy of Cognitive Behavioral Therapy With and Without Medication for Adults
With ADHD.
AB - OBJECTIVE: Recent trials have demonstrated efficacy of cognitive behavioral
therapy (CBT) in medicated adults with ADHD. Efficacy of CBT in unmedicated
versus medicated adults remains mostly unknown. We evaluated the effects of group
CBT alone versus combined with medication on ADHD symptoms and functional
outcomes in adult patients. METHOD: Eighty-eight adults with ADHD received 12
manualized group CBT sessions, accompanied by individual coaching, either without
( n = 46) or with ( n = 42) medication. Treatment effects were evaluated
following treatment and 3-month and 6-month follow-up using un-blinded self
report and observer ratings. RESULTS: CBT + medication resulted in greater
improvements than CBT alone in ADHD symptoms, organizational skills, and self
esteem. Group differences diminished over follow-up, as the CBT alone group
continued improving, while the combined group maintained the gains. CONCLUSION:
CBT + medication outperformed CBT alone for ADHD symptoms, organizational skills,
and self-esteem, although its superiority tended to decrease over follow-up.
PMID- 28413902
TI - Sustainable development goals and road traffic injuries: the new research
challenge.
PMID- 28413901
TI - Elevation of CD16+CD56+ NK-cells and down-regulation of serum interleukin-21 (IL
21) and IL-1alpha after splenectomy in relapsed hemophagocytic
lymphohistiocytosis of unknown cause.
AB - OBJECTIVES: Encouraging progress has been made in application of splenectomy in
the treatment of relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown
cause. The aim was to determine the roles of lymphocyte subpopulations and
inflammatory cytokines in splenectomy. METHODS: We retrospectively analyzed
changes in lymphocyte subpopulations and levels of inflammatory cytokines at
different time-points before and after splenectomy in the patients with relapsed
HLH of unknown cause, as well as the correlations between these changes and the
disease prognosis. RESULTS: During the period from June 2006 to June 2016, we
enrolled 107 patients with relapsed HLH of unknown cause, of whom 29 were treated
with splenectomy. Among the 29 patients, 7 cases were non-Hodgkin lymphomas based
on spleen pathology, 1 case withdrew and the remaining 21 non-lymphoma cases were
available for analysis. Results showed a significant increase in both percentage
of CD16+CD56+ NK cells (P = 0.003) and NK cell activity (P = 0.028) at 24 wk
after splenectomy compared to their baseline pre-surgery levels. We also examined
seven patients for the changes in cytokine levels before and after splenectomy
and found that IL-21 and IL-1alpha decreased at 4 wk after splenectomy (P <
0.05). Seven non-lymphoma patients determined as no response to treatment (NR)
prior to splenectomy had significantly longer survival (P = 0.001) compared to
the 24 patients with relapsed HLH of unknown cause who were also determined as NR
but not treated by splenectomy. DISCUSSION: Splenectomy can improve clinical
symptoms and survival of patients with relapsed HLH of unknown cause. The
mechanism is likely related to the changes in percent NK cells and cytokines (IL
21 and IL-1alpha) after surgery.
PMID- 28413903
TI - Digital revascularization and replantation using the wide-awake hand surgery
technique.
AB - : The use of local anaesthesia and adrenaline for hand surgery is gaining
popularity; however, where vascularity is impaired, wide-awake surgery is
considered a contraindication. We present our case series of five digital
devascularizations and eight amputations that underwent surgery using the 'wide
awake' anaesthetic technique. A temporary digital tourniquet (< 20 min) was used
in three cases to identify structures quickly. The anastomoses were performed
under local anaesthesia without a tourniquet. All cases had successful re
establishment of blood flow with good perfusion to the digital tips; no cases
were re-explored because of vascular crisis. Four cases had minor superficial
soft tissue necrosis that healed secondarily. We conclude that digital
revascularization and replantation can be performed under local anaesthesia with
use of adrenaline and without detriment to the traumatized digit provided careful
patient selection and adequate operator experience are available. LEVEL OF
EVIDENCE: IV.
PMID- 28413904
TI - Helicobacter Pylori Infection in Texas Hispanic and Non-Hispanic White Men:
Implications for Gastric Cancer Risk Disparities.
AB - Chronic Helicobacter pylori ( H. pylori) infection is a major gastric
adenocarcinoma (GA) risk factor. GA disproportionately affects U.S. Hispanics
compared with non-Hispanic Whites (NHWs). Since H. pylori infection studies in
Hispanics are few, infection rates in Hispanic and NHW men in Bexar County were
compared, and relationships with ethnicity and obesity examined. Age- and zip
code-matched participants from a community-dwelling cohort were randomly
selected. Sera from 284 men were analyzed by enzyme immunoassay for H. pylori
antibodies. Adjusted risk ratio estimation for matched data was conducted to
identify differences. Hispanics had a markedly higher prevalence of infection
(30.3%) than NHWs (9.2%). Matched risk ratio (mRR) analyses revealed a strong
association between H. pylori seropositivity and Hispanic ethnicity (mRR = 3.31;
95% CI [1.91, 5.73], adjusted by BMI, smoking status, and family history of
cancer (mRR range = 3.28-3.89). BMI mRRs (range = 1.19-1.22) were significant in
all models. In this cohort, Hispanic men had higher H. pylori infection rates
than NHWs, and parallel the disproportionately higher rates of GA; obesity
contributes to this higher prevalence. Future studies should address country of
origin, acculturation, and other factors influencing obesity to further elucidate
risk of GA in Hispanic populations.
PMID- 28413905
TI - Pre-meal inulin consumption does not affect acute energy intake in overweight and
obese middle-aged and older adults: A randomized controlled crossover pilot
trial.
AB - BACKGROUND: Three-fourths of adults older than 55 years in the United States are
overweight or obese. Prebiotics including inulin-type fructans may benefit with
weight management. AIM: We aimed to investigate the acute effects of pre-meal
inulin consumption on energy intake (EI) and appetite in older adults. METHODS:
Sedentary, overweight or obese middle-aged and older adults ( n = 7, 60.9 +/- 4.4
years, BMI 32.9 +/- 4.3 kg/m2) ingested inulin (10 g) or a water preload before
each test period in a randomly assigned order. EI, appetite and gastrointestinal
symptoms were monitored during the following 24 h. RESULTS: No differences in EI
were noted between conditions (inulin: 14744 +/- 5552 kJ, control: 13924 +/- 4904
kJ, p > 0.05). Rumbling was increased with inulin consumption ( p < 0.05).
CONCLUSION: Pre-meal inulin consumption does not acutely decrease EI or suppress
appetite in older adults. Further research should address individual differences
among diets, eating behaviors, and microbiota profiles.
PMID- 28413906
TI - Development and Validation of the Masculine Attributes Questionnaire.
AB - The present study describes the development and validation of the Masculine
Attributes Questionnaire (MAQ). The purpose of this study was to develop a
theoretically and empirically grounded measure of masculine attributes for sexual
health research with African American young men. Consistent with Whitehead's
theory, the MAQ items were hypothesized to comprise two components representing
reputation-based and respect-based attributes. The sample included 505 African
American men aged 19 to 22 years ( M = 20.29, SD = 1.10) living in resource-poor
communities in the rural South. Convergent and discriminant validity of the MAQ
were assessed by examining the associations of masculinity attributes with
psychosocial factors. Criterion validity was assessed by examining the extent to
which the MAQ subscales predicted sexual risk behavior outcomes. Consistent with
study hypotheses, the MAQ was composed of (a) reputation-based attributes
oriented toward sexual prowess, toughness, and authority-defying behavior and (b)
respect-based attributes oriented toward economic independence, socially approved
levels of hard work and education, and committed romantic relationships.
Reputation-based attributes were associated positively with street code and
negatively related to academic orientation, vocational engagement, and self
regulation, whereas respect-based attributes were associated positively with
academic and vocational orientations and self-regulation. Finally, reputation
based attributes predicted sexual risk behaviors including concurrent sexual
partnerships, multiple sexual partners, marijuana use, and incarceration, net of
the influence of respect-based attributes. The development of the MAQ provides a
new measure that permits systematic quantitative investigation of the
associations between African American men's masculinity ideology and sexual risk
behavior.
PMID- 28413907
TI - Interaction of dextromethorphan hydrobromide with DNA: multispectral,
voltammetric, and molecular docking technology.
PMID- 28413909
TI - Sticking to the (romantic) script: an examination of love life scripts, stories,
and self-reports of normality.
AB - Life scripts represent cultural expectations regarding the events in the
prototypical life whereas life stories represent narrative constructions of the
events occurring in individuals' own lives. In Study 1, we generated an outline
of the love life script and a list of the self-definitional events individuals
tend to associate with their own love lives. Participants were prompted to
produce and rate seven important events in the prototypical love life and several
significant moments from their own love lives. Building upon these descriptive
efforts, in Study 2, we developed self-report measures of perceived and desired
love life normality. These characteristics positively predicted the
conventionality of autobiographical narratives drawn from participants' love life
stories. Furthermore, perceived normality and desired normality were positively
and negatively related to functioning within the romantic domain, respectively.
These results underscore the role love life scripts and love life stories play in
functioning within the romantic domain.
PMID- 28413910
TI - Phenotypic characterization of late onset cardiac amyloidosis caused by the
transthyretin mutation TTRA45S, p.(Ala65Ser).
PMID- 28413908
TI - Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney
diseases: an update.
AB - Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which
epithelial cells lose their hallmark epithelial characteristics and gain the
features of mesenchymal cells. For podocytes, expression of nephrin, podocin, P
cadherin, and ZO-1 is downregulated, the slit diaphragm (SD) will be altered, and
the actin cytoskeleton will be rearranged. Diabetes, especially hyperglycemia,
has been demonstrated to incite podocyte EMT through several molecular mechanisms
such as TGF-beta/Smad classic pathway, Wnt/beta-catenin signaling pathway,
Integrins/integrin-linked kinase (ILK) signaling pathway, MAPKs signaling
pathway, Jagged/Notch signaling pathway, and NF-kappaB signaling pathway. As one
of the most fundamental prerequisites to develop ground-breaking therapeutic
options to prevent the development and progression of diabetic kidney disease
(DKD), a comprehensive understanding of the molecular mechanisms involved in the
pathogenesis of podocyte EMT is compulsory. Therefore, the purpose of this paper
is to update the research progress of these underlying signaling pathways and
expound the podocyte EMT-related DKDs.
PMID- 28413911
TI - Recurrence rate after thoracoscopic surgery for primary spontaneous pneumothorax.
AB - OBJECTIVES: There is an on-going discussion regarding the recurrence rate after
surgery for primary spontaneous pneumothorax by video assisted thoracic surgery
(VATS) or by thoracotomy access. This study aimed to describe the recurrence
rate, and to identify a possible learning curve, following surgery for primary
spontaneous pneumothorax by VATS. DESIGN: All patients who underwent surgery for
primary spontaneous pneumothorax by VATS at Karolinska University Hospital 2004
2013 were reviewed. Preoperative and operative characteristics were obtained from
medical records. Patients were followed-up through telephone interviews or
questionnaires and by review of medical records. The primary outcome of interest
was time to recurrence of pneumothorax requiring intervention. Outcomes were
compared between patients operated during 2004-June 2010 and July 2010-2013.
RESULTS: 219 patients who underwent 234 consecutive procedures were included. The
mean follow-up times were 6.3 and 2.9 years in the early and late period,
respectively. The postoperative recurrence rate in the early period was 16% (11%
25%), 18% (12%-27%), and 18% (12%-27%), at 1, 3 and 5 years, compared to 1.7%
(0.4%-6.8%), 7.6% (3.7%-15%), and 9.8% (4.8%-19%) at 1, 3 and 5 years, in the
late period (p = 0.016). CONCLUSIONS: We found that the recurrence rate after
thoracoscopic surgery for primary spontaneous pneumothorax decreased
significantly during the study period. Our results strongly suggest that
thoracoscopic surgery for pneumothorax involve a substantial learning curve.
PMID- 28413912
TI - The acute effects of baobab fruit ( Adansonia digitata) on satiety in healthy
adults.
AB - BACKGROUND: The baobab fruit is high in both dietary fibre and polyphenols and
therefore may increase satiety. The aim of the study was to measure the effects
of baobab fruit extract on satiety. METHODS: The study was conducted on 20
healthy participants. The study was a one-day single-blind crossover design.
Participants were randomised to either a test smoothie consisting of 15 g of
baobab extract or a control smoothie without the addition of baobab. Subjective
ratings of satiety were taken on visual analogue scales immediately pre
consumption and then post-consumption, and energy intake at a post ad libitum
meal was recorded. RESULTS: Subjective measures of hunger were reduced following
the test smoothie compared with the control ( p < 0.05). There was no significant
difference in calorie intake at an ad libitum meal. CONCLUSIONS: This research
has positive implications for the use of baobab for reducing hunger, possibly
having a positive effect on weight maintenance.
PMID- 28413913
TI - Sertoliform Cystadenoma of the Rete Testis: Report of a Case and Review of the
Literature.
AB - Sertoliform cystadenoma is a rare benign tumor of the rete testis with 8
previously reported cases and an additional 14 cases reported in an abstract
form. It usually presents with a unilateral scrotal mass, clinically and
radiologically indistinguishable from malignant testicular tumors. We report a 39
year-old man who presented with a right testicular mass. The patient underwent
radical inguinal orchiectomy. Grossly, no masses were appreciated. After
histologic examination with subsequent immunohistochemical staining, a
sertoliform cystadenoma of the rete testis was diagnosed.
PMID- 28413914
TI - Prognostic value of the soluble interleukin-2 receptor level after patients with
follicular lymphoma achieve a response to R-CHOP.
AB - OBJECTIVES: Follicular lymphoma (FL) is a clinically and biologically
heterogeneous disease. Therefore, it is important to identify factors that can
predict its clinical outcome. METHODS: We retrospectively evaluated the
usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP
(posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a
complete response (CR) or partial response. With the use of a recursive
partitioning analysis, we determined the cut-off values of post- and pretreatment
sIL-2R levels that were associated with disease progression, which corresponded
to 486.5 and 5405 U/mL, respectively. RESULTS: The high posttreatment sIL-2R
group showed a significantly inferior progression-free survival (PFS) compared to
the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P
= 0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P = 0.034).
Although a multivariate analysis showed that pretreatment sIL-2R, but not
posttreatment sIL-2R, was an independently significant predictive factor for
disease progression, among patients with low pretreatment sIL-2R levels, those
with high posttreatment sIL-2R levels tended to have inferior PFS. There was a
significant trend in PFS among the high pretreatment sIL-2R group, the low pre-
and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL
2R group (P < 0.001). CONCLUSION: Among patients with a low pretreatment sIL-2R
level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level
may help to identify those with a poor prognosis.
PMID- 28413915
TI - Oxidative stress status in congenital hypogonadism: an appraisal.
AB - Patients with hypogonadism are at increased risk of cardiac and metabolic
diseases. However, the pathogenesis of increased cardiometabolic risk in patients
with hypogonadism is not clear. Oxidative stress plays an important role in the
pathogenesis of cardiometabolic diseases. This study aimed to investigate
possible differences in oxidative stress conditions between patients with
hypogonadism and healthy controls. In this study, 38 male patients with
congenital hypogonadotropic hypogonadism (CHH) (mean age: 21.7 +/- 1.6 years) and
44 healthy male controls (mean age: 22.3 +/- 1.4 years) with almost equal body
mass index were enrolled. The demographic parameters, follicle-stimulating
hormone (FSH), luteinizing hormone (LH), total and free testosterone, homeostatic
model assessment of insulin resistance (HOMA-IR) and oxidative stress parameters,
such as superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx) and
malondialdehyde (MDA), were compared between both groups. Compared to the healthy
controls, triglycerides (p = .02), insulin levels, HOMA-IR values, CAT activities
and MDA levels (p < .001 for all) were significantly higher and HDL cholesterol
(p = .04), total and free testosterone, FSH, LH levels and GPx activity were
significantly lower (p < .001 for all) in patients with CHH. There were
significant correlations between total testosterone levels and CAT activity (r =
.33 p = .01), GPx activity (r = .36 p = .007) and MDA (r = -.47 p < .001) levels.
The results of this study showed that young and treatment-naive patients with
congenital hypogonadism had an increased status of oxidative stress.
PMID- 28413916
TI - Extent of allergic inflammation depends on intermittent versus continuous
sensitization to house dust mite.
AB - OBJECTIVE: House dust mite (HDM) exposure is used to model experimental asthma in
mice. However, a direct comparison of inflammatory responses following continuous
versus intermittent HDM exposure has not been reported. Therefore, we
investigated whether the HDM dose at sensitization or challenge affects extent of
inflammation in mice that were either continuously or intermittently sensitized
with HDM. MATERIALS AND METHODS: C57BL/6 mice received either 10 continuous
exposures with 10 MUg HDM per exposure or two intermittent HDM exposures over a
period of two weeks and were subsequently challenged by three instillations with
HDM during the third week. For the intermittent model, mice were sensitized with
1 or 10 MUg HDM and challenged on three consecutive days with 1 or 10 MUg HDM.
Inflammatory cells in the bronchoalveolar lavage fluid and epithelial cell
hyperplasia and mucous cell metaplasia were quantified. RESULTS: Significantly
higher levels of inflammation and mucous cell metaplasia were observed when mice
were sensitized intermittently compared with continuously. Intermittent
sensitization and challenge with 10 MUg HDM caused maximum inflammation, mucous
cell metaplasia, and epithelial cell hyperplasia. However, sensitization with 1
MUg HDM only also showed increased inflammation when challenged with 10 MUg HDM.
DISCUSSION: These findings suggest major differences in adaptive immunity,
depending on the sensitization protocol. CONCLUSIONS: Because of significant
differences, the HDM sensitization protocol should be carefully considered when
designing studies to investigate the underlying mechanisms of immunity in mouse
models of asthma.
PMID- 28413918
TI - Mothers Who Were Neglected in Childhood Show Differences in Neural Response to
Their Infant's Cry.
AB - The present study used functional magnetic resonance imaging to investigate how a
mother's experience of neglect in her own childhood is associated with her neural
response to her infant's distress cues. During scanning, 22 high-risk primiparous
mothers were exposed to both their own 18-month-old infant's cry sound and a
control sound. Mothers' continuous Neglect subscale scores from the Childhood
Trauma Questionnaire were examined as a predictor of their neural response to own
infant cry > control sound. Mothers who reported high levels of neglect from
childhood showed regions of hyperactivation to their infant's cry (relative to
control sound) in the anterior and posterior cingulate cortices and insula as
well as specific prefrontal (precentral gyrus) and parietal (posterior
supramarginal gyrus) areas. These results may suggest how important early life
experiences are for future parenting responses and behaviors.
PMID- 28413919
TI - Examining Child Welfare Decisions and Services for Asian-Canadian Versus White
Canadian Children and Families in the Child Welfare System.
AB - Using administrative child welfare data from the Ontario Child Abuse and Neglect
Data System (OCANDS), this study compared the profiles of Asian-Canadian and
White-Canadian children and families that experienced a case closure after an
investigation instead of being transferred to ongoing child protection services
(CPS). Child protection investigations involving Asian-Canadian and White
Canadian children and families that were transferred to ongoing CPS presented a
different profile of case characteristics and caregiver and child clinical needs.
Asian-Canadian children and families received ongoing CPS for over a month longer
than White-Canadian children and families and were less likely (odds ratio [ OR]
= 0.39) to be reinvestigated for any form of maltreatment-related concerns within
1 year after case closure. It appears that child protection investigations
involving Asian-Canadian children and families are less likely to be closed
prematurely than White-Canadian children and families, and the child protection
system may be meeting the needs of Asian-Canadian communities. Alternatively, it
is possible there is unaccounted biases that may be reflective of systemic
problem of discriminative practices in the child protection system. Further
research is needed to explore this phenomenon.
PMID- 28413917
TI - Is the Families First Home Visiting Program Effective in Reducing Child
Maltreatment and Improving Child Development?
AB - While home visiting programs are among the most widespread interventions to
support at-risk families, there is a paucity of research investigating these
programs under real-world conditions. The effectiveness of Families First home
visiting (FFHV) was examined for decreasing rates of being in care of child
welfare, decreasing hospitalizations for maltreatment-related injuries, and
improving child development at school entry. Data for 4,562 children from home
visiting and 5,184 comparison children were linked to deidentified administrative
health, social services, and education data. FFHV was associated with lower rates
of being in care by child's first, second, and third birthday (adjusted risk
ratio [aRR] = 0.75, 0.79, and 0.81, respectively) and lower rates of
hospitalization for maltreatment-related injuries by third birthday (aRR = 0.59).
No differences were found in child development at kindergarten. FFHV should be
offered to at-risk families to decrease child maltreatment. Program enhancements
are required to improve child development at school entry.
PMID- 28413920
TI - First Births to Maltreated Adolescent Girls: Differences Associated With Spending
Time in Foster Care.
AB - Few studies have examined early parenting among girls receiving child welfare
services (CWS) or disentangled the relationship between maltreatment, spending
time in foster care, and adolescent childbirth. Using population-based, linked
administrative data, this study calculated birth rates among maltreated
adolescent girls and assessed differences in birth rates associated with spending
time in foster care. Of the 85,766 girls with substantiated allegations of
maltreatment during adolescence, nearly 18% subsequently gave birth. Among girls
who spent time in foster care, the proportion was higher (19.5%). Significant
variations ( p < .001) were observed in the rate of childbirth across demographic
characteristics and maltreatment experiences. When accounting for all of the
covariates, spending time in foster care was associated with a modestly higher
rate of a first birth (Hazard Ratio [HR] = 1.10; 95% confidence interval = [1.06,
1.14]). While age at first substantiated allegation of maltreatment and
race/ethnicity were significant predictors of adolescent childbirth, specific
maltreatment experiences were associated with minimal or no differences in birth
rates. The findings of this study suggest that the experience of spending time in
care may not be a meaningful predictor of giving birth as a teen among CWS
involved adolescent girls and highlight subgroups of this population who may be
more vulnerable to early childbirth.
PMID- 28413922
TI - Child Maltreatment Welcomes New Board Members.
PMID- 28413921
TI - Preventing the Onset of Child Sexual Abuse by Targeting Young Adolescents With
Universal Prevention Programming.
AB - Child sexual abuse (CSA) is a serious public health problem that increases risk
for physical and mental health problems across the life course. Young adolescents
are responsible for a substantial portion of CSA offending, yet to our knowledge,
no validated prevention programs that target CSA perpetration by youth exist.
Most existing efforts to address CSA rely on reactive criminal justice policies
or programs that teach children to protect themselves; neither approach is well
validated. Given the high rates of desistance from sexual offending following a
youth's first CSA-related adjudication, it seems plausible that many youth could
be prevented from engaging in their first offense. The goal of this article is to
examine how school-based universal prevention programs might be used to prevent
CSA perpetrated by adolescents. We review the literature on risk and protective
factors for CSA perpetration and identify several promising factors to target in
an intervention. We also summarize the literature on programs that have been
effective at preventing adolescent dating violence and other serious problem
behaviors. Finally, we describe a new CSA prevention program under development
and early evaluation and make recommendations for program design characteristics,
including unambiguous messaging, parental involvement, multisession dosage,
skills practice, and bystander considerations.
PMID- 28413923
TI - Knowledge of healthy foods does not translate to healthy snack consumption among
exercise science undergraduates.
AB - This cross-sectional survey study compared the on- and off-campus snack choices
and related correlates of convenience samples of exercise science (ES) ( n = 165,
M = 45%, F = 55%) and non-exercise science (NES) ( n =160, M = 43%, F = 57%)
undergraduates. The hypothesis posed was that knowledge of healthy foods will not
translate to healthier snack consumption by the ES students, and that the snack
choices and related correlates of ES and NES students will be similar. Data were
collected using self-administered questionnaires completed in classrooms (ES
sample) and at high-traffic locations on-campus (NES sample). Chi-square and t
test analyses compared ES and NES students on snack correlates. Snacks consumed
most often by the ES and NES students on-campus were health bars/squares ( n = 56
vs. n = 48) and savory snacks ( n = 55 vs. n = 71), and off-campus were savory
snacks ( n = 60 vs. n = 71) and fruits ( n = 41 vs. n = 34). Over half of both
samples believed their snack choices were a mix of unhealthy and healthy. Fruits
were considered healthier snacks and chips less healthy by both samples, and
fruits were the most often recommended snack. About 20% believed these choices
would impact their health unfavorably, and about two thirds self-classified in
the action stages for healthy snacking. Since knowledge about healthy food
choices did not translate to healthy snack selection, these students would
benefit from interventions that teach selection and preparation of healthy snacks
on a restricted budget.
PMID- 28413924
TI - Erythropoietin attenuates axonal injury after middle cerebral artery occlusion in
mice.
AB - OBJECTIVE: Erythropoietin (EPO) confers potent neuroprotection against ischemic
injury through a variety of mechanisms. However, the protective effect of EPO on
axons after cerebral ischemia in adult mice is rarely covered. The purpose of
this study was to investigate the potential neuroprotective effects of EPO on
axons in mice after cerebral ischemia. METHODS: A total of 30 adult male C57 BL/6
mice were treated with EPO (5000 IU/kg) or vehicle after transient middle
cerebral artery occlusion (MCAO). The mortality rate of each experimental group
was calculated. Neurological function was assessed by Rota-rod test. Frozen
sections from each mouse brain at 14 days after reperfusion were used to evaluate
the fluorescent intensity of myelin basic protein (MBP) and neurofilament 200 (NF
200). Immunofluorescence staining and Western blotting were used to assess the
protein level of beta-amyloid precursor protein (beta-APP) and glial fibrillary
acidic protein (GFAP), a marker of mature astrocytes. The protein levels of the
myelin-derived growth inhibitory proteins, neurite growth inhibitor-A (Nogo-A),
myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein
(OMG) were also examined by Western blot after MCAO. RESULTS: The survival rate
of the vehicle group 14 days after cerebral ischemia-reperfusion was 50%, which
increased to 80% after EPO treatment at the start of reperfusion. EPO improved
neurobehavioral outcomes at days 3 and 7 after MCAO was compared with the vehicle
group (P < 0.05). Furthermore, EPO ameliorated demyelination, demonstrated by
upregulation of the MBP/NF-200 ratio. Meanwhile, increased levels of beta-APP,
GFAP, Nogo-A, and MAG after MCAO were reduced by EPO treatment (P < 0.05).
CONCLUSION: EPO treatment attenuates axonal injury and improves neurological
function after cerebral ischemia in adult mice.
PMID- 28413925
TI - Triple-Bead Mixed Amphetamine Salts (SHP465) in Adults With ADHD: Results of a
Phase 3, Double-Blind, Randomized, Forced-Dose Trial.
AB - OBJECTIVE: Evaluate the efficacy and tolerability of triple-bead mixed
amphetamine salts (MAS) in ADHD. METHOD: Adults with ADHD Rating Scale IV (ADHD
RS-IV) total scores >=32 were randomized to 6 weeks of triple-bead MAS (25, 50,
or 75 mg) or placebo. The primary endpoint was ADHD-RS-IV total score change from
baseline at end of study (EOS). RESULTS: Least squares mean (95% confidence
interval [CI]) treatment differences for ADHD-RS-IV total score changes from
baseline to EOS significantly favored triple-bead MAS (all doses combined: -10.6
[-13.2, -8.0]; p < .0001); there were no significant differences between triple
bead MAS dosages. The most frequently reported TEAEs with triple-bead MAS (all
doses combined) included insomnia, decreased appetite, and dry mouth. Mean +/- SD
pulse and systolic blood pressure increases at EOS were 3.5 +/- 10.33 bpm and 0.3
+/- 10.48 mmHg with triple-bead MAS (all doses combined). CONCLUSION: Triple-bead
MAS significantly reduced adult ADHD symptoms; the safety profile was consistent
with previous triple-bead MAS studies.
PMID- 28413926
TI - DUSP-1 gene expression is not regulated by promoter methylation in diabetes
associated cardiac hypertrophy.
AB - BACKGROUND: The exact mechanism causing decreased expression of the dual specific
phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not
known. DNA promoter methylation is often associated with decreased gene
expression in many diseases including cardiovascular diseases. So, we
investigated whether epigenetic silencing via promoter methylation is involved in
the decreased expression of DUSP-1 in diabetes-associated cardiac hypertrophy.
METHODS: Real-time polymerase chain reaction (PCR) and Western blotting confirmed
the down regulation of the DUSP-1 gene at transcriptional and translational
levels. Bisulfite-converted DNA samples from myocardium of rat model of diabetic
cardiomyopathy (DCM), high glucose (HG)-treated neonatal rat cardiomyocytes
(NRCMs) and cardiac tissues from archived human myocardial DCM autopsies along
with their respective controls were analyzed for methylation in the promoter
region of the DUSP-1 gene. RESULTS: We observed no methylation in the promoter
regions of the DUSP-1 gene in DCM rat hearts, in HG-treated NRCMs (between -355
bp and -174 bp) and in cardiac tissues from archived human myocardial DCM
autopsies (between -274 bp and -73 bp). CONCLUSION: Methylation-mediated
silencing of the DUSP-1 promoter does not appear to be associated with reduced
expression, indicating the involvement of other factors in specific suppression
of DUSP-1 in diabetes-associated cardiac hypertrophy.
PMID- 28413927
TI - "It Has Changed My Life": An Exploration of Caregiver Experiences in Serious
Illness.
AB - BACKGROUND: Informal, unpaid caregivers shoulder much of the care burden for
individuals with serious illness. As part of a project to create an innovative
model of supportive care for serious illness, a series of user interviews were
conducted, forming the basis for this article. OBJECTIVE: To understand both
individual and interpersonal aspects of caregiving for serious illness. METHODS:
Twelve semistructured group interviews were conducted with patients, families,
and professionals as part of a larger study of late-life serious illness.
Transcript data were analyzed with descriptive coding, and then coded material
was analyzed to elicit major themes and subthemes. RESULTS: A total of 73
individuals participated in group interview sessions. Using descriptive coding,
quotes were assigned to first-order codes of rewards, challenges, and a category
of learnings and adaptations. Subthemes of reward included gratitude, a sense of
accomplishment or mastery, and closeness in personal relationships. The most oft
cited challenges included emotional and physical stresses of caregiving and
feeling unprepared or unsupported in caregiving. Reflecting on their experiences,
caregivers cited new ways in which they had learned to be creative, to show
assertiveness and advocacy, and to create personal balance in a demanding
situation. CONCLUSIONS: The experience of caregiving is a life-altering journey
as individuals rise to challenges and reflect on the rewards. Caregivers
described intensive caregiving, often without acknowledgment or understanding of
their role from the health-care system. This invisibility created its own
iatrogenic caregiving challenge. The identified themes suggest avenues of
meaningful caregiver support that bear further exploration.
PMID- 28413928
TI - The Oncology Specialist's Role in POLST Form Completion.
AB - INTRODUCTION: Patients with cancer and oncology professional societies believe
that advance care planning is important, but we know little of who actually has
this conversation. Physician Orders for Life-Sustaining Treatment (POLST) forms
can help to document these important conversations to ensure patients receive the
level of treatment they want. We therefore sought to determine the specialty of
those signing POLST forms for patients who died of cancer to better understand
who is having this discussion with patients. METHODS: Retrospective cohort study
including all deaths due to cancer in Oregon between January 1, 2010, and
December 31, 2011. Death certificates were matched to POLST forms in the Oregon
POLST Registry, and the signing physician's specialty was determined using the
Oregon Medical Board's database. RESULTS: A total of 14 979 people died of cancer
in Oregon in 2010 to 2011. Of which, 6145 (41.0%) had at least 1 POLST form in
the Registry. Oncology specialists signed 14.9% of POLST forms, compared to 53.7%
by primary care, 15.3% by hospice/palliative care, 12.8% by advanced practice
providers, and 2.7% by other specialists; 51.8% of oncology specialists did not
sign a POLST form, whereas 12.5% completed 10 or more. CONCLUSION: Oncology
specialists play a central role in caring for patients with cancer through the
end of their lives, but not in POLST completion. Whether or not they actually
sign their patients' POLST forms, oncology specialists in the growing number of
POLST states should integrate POLST into their goals of care conversations with
patients nearing the end of life.
PMID- 28413929
TI - Nurses' Interest in Independently Initiating End-of-Life Conversations and
Palliative Care Consultations in a Suburban, Community Hospital.
AB - BACKGROUND: Patients who receive early palliative care consults have clinical
courses and outcomes more consistent with their goals. Nurses have been shown to
be advocates for early palliative care involvement and are able to lead advanced
care planning discussions. OBJECTIVE: The purpose of this study was to assess
whether after a brief educational session, nurses at a suburban, community
hospital could demonstrate knowledge of palliative care principles, would want to
independently initiate end-of-life conversations with patients and families, and
would want to place specialty palliative care consults. DESIGN: Four 1 hour
presentations were made at 4 nursing leadership council meetings from November
through December 2015. Anonymous pre- and post-presentation surveys were
distributed and collected in person. Setting/Participant: Nonprofit, suburban,
community hospital in Maryland. Participants were full-time or part-time hospital
employees participating in a nursing leadership council who attended the
presentation. MEASUREMENTS: We compared responses from pre- and post-presentation
surveys. RESULTS: Fifty nurses (19 departments) completed pre-presentation
surveys (100% response rate) and 49 nurses completed post-presentation surveys
(98% response rate). The average score on 7 index questions increased from 71% to
90%. After the presentations, 86% strongly agreed or agreed that nurses should be
able to independently order a palliative care consult and 88% strongly agreed or
agreed with feeling comfortable initiating an end-of-life conversation.
CONCLUSION: Brief educational sessions can teach palliative care principles to
nurses. Most participants of the study would want to be able to directly consult
palliative care and would feel comfortable initiating end-of-life conversations
after this educational session.
PMID- 28413930
TI - Relationship of Genetic Variants With Procedural Pain, Anxiety, and Distress in
Children.
AB - OBJECTIVE: This study used a candidate gene approach to examine genomic variation
associated with pain, anxiety, and distress in children undergoing a medical
procedure. STUDY DESIGN: Children aged 4-10 years having an IV catheter insertion
were recruited from three Midwestern children's hospitals. Self-report measures
of pain, anxiety, and distress were obtained as well as an observed measure of
distress. Samples were collected from children and biological parents for
analysis of genomic variation. Genotyped variants had known or suspected
association with phenotypes of interest. Analyses included child-only association
and family-based transmission disequilibrium tests. RESULTS: Genotype and
phenotype data were available from 828 children and 376 family trios. Children
were 50% male, had a mean age of 7.2 years, and were 84% White/non-Hispanic. In
family-based analysis, one single-nucleotide polymorphism (SNP; rs1143629,
interleukin ( IL1B) 1beta) was associated with observed child distress at
Bonferroni-corrected levels of significance ( p = .00013), while two approached
significance for association with high state anxiety (rs6330 Nerve Growth Factor,
Beta Subunit, [ NGFB]) and high trait anxiety (rs6265 brain-derived neurotrophic
factor [ BDNF]). In the child-only analysis, multiple SNPs showed nominal
evidence of relationships with phenotypes of interest. rs6265 BDNF and rs2941026
cholecystokinin B receptor had possible relationships with trait anxiety in child
only and family-based analyses. CONCLUSIONS: Exploring genomic variation furthers
our understanding of pain, anxiety, and distress and facilitates genomic
screening to identify children at high risk of procedural pain, anxiety, and
distress. Combined with clinical observations and knowledge, such explorations
could help guide tailoring of interventions to limit procedure-related distress
and identify genes and pathways of interest for future genotype-phenotype
studies.
PMID- 28413931
TI - Glucose Variations and Activity Are Strongly Coupled in Sleep and Wake in Young
Adults With Type 1 Diabetes.
AB - BACKGROUND: Glucose variations are common throughout sleep and wakefulness in
people with type 1 diabetes mellitus (T1DM). The objective of this investigation
was to characterize the time-varying coupling between glucose and unstructured
physical activity over a 60-hr period in young adults with T1DM. The hypothesis
was that coupling would differ during sleep versus wakefulness and would exhibit
circadian variations. METHOD: Young adults with T1DM treated with an insulin pump
participated in the study. Glucose variations were monitored with a continuous
glucose monitoring system, and activity was assessed using an activity-monitoring
band worn on the nondominant wrist. Simultaneous glucose and physical activity
data across a continuous 60-hr period were used for analysis. Wavelet coherence
analysis was employed to quantify the coupling between physical activity and
glucose. Cosinor analysis was used to assess whether glucose/activity coherence
exhibited significant circadian variations. RESULTS: Participants comprised 23
adults, aged 18-30 years, with T1DM. Coherence analysis demonstrated substantial
coupling between physical activity and glucose variations during both wakefulness
and sleep. For rapid (10-30 min) fluctuations, mean coherence was higher during
sleep than wakefulness ( F = 10.86, p = .003). Rapid glucose variations
consistently led to changes in activity ( p = .001) during sleep but not during
wake. Cosinor analysis revealed significant circadian modulation of
glucose/activity coupling, especially for fluctuation periods 2-4 hr.
CONCLUSIONS: Unstructured physical activity and glucose variations demonstrated
strong time- and frequency-dependent coupling over a 60-hr period in young adults
with T1DM, with sleep/wake differences and circadian modulation evident in this
relationship.
PMID- 28413933
TI - Primer in Genetics and Genomics, Article 3-Explaining Human Diversity: The Role
of DNA.
AB - Genetic variation lays the foundation for diversity and enables humans to adapt
to changing environments. The order of the nucleotides adenine, guanine,
cytosine, and thymine on the deoxyribonucleic acid (DNA) molecules of the nuclear
chromosomes and mitochondrial DNA (mtDNA) plays an important role in normal cell
division, tissue development, and reproduction but is susceptible to alteration
from a large number of random, inherited, or environmental events. Variations can
range from a change in a single nucleotide to duplication of entire chromosomes.
Single nucleotide polymorphisms are the major source of human heterogeneity.
Other variations that can alter phenotypes and adversely impact growth,
development, and health include copy number variations, aneuploidies, and
structural alterations such as deletions, translocations, inversions,
duplications, insertions, or mutations in mtDNA. In addition, DNA rearrangements
in somatic cells underlie the uncontrolled cell growth found in cancer. This
article explores the mechanisms by which variations in DNA arise and the impact
those changes can have on human health.
PMID- 28413934
TI - Commonly used air filters fail to eliminate secondhand smoke induced oxidative
stress and inflammatory responses.
AB - Secondhand smoke (SHS) causes approximately 50,000 deaths per year. Despite all
the health warnings, smoking is still allowed indoors in many states exposing
both workers and patrons to SHS on a daily basis. The opponents of smoking bans
suggest that present day air filtration systems remove the health hazards of
exposure to SHS. In this study, using an acute SHS exposure model, we looked at
the impact of commonly used air filters (MERV-8 pleated and MERV-8 pleated
activated charcoal) on SHS by assessing the inflammatory response and the
oxidative stress response in C57BL/6 mice. In order to assess the inflammatory
response, we looked at the tumor necrosis factor alpha (TNF-alpha) cytokine
production by alveolar macrophages (AMs), and for the oxidative response, we
quantified the products of lipid peroxidation and the total glutathione (tGSH)
production in lung homogenates. Our results showed that SHS caused significant
immune and oxidative stress responses. The tested filters resulted in only a
modest alleviation of inflammatory and oxidative responses due to SHS exposure.
Our data show that these air filters cannot eliminate the risk of SHS exposure
and that a short-term exposure to SHS is sufficient to alter the inflammatory
cytokine response and to initiate a complex oxidative stress response. Our
results are consistent with the statement made by the Surgeon General's reports
that there is no risk free level of exposure to SHS.
PMID- 28413935
TI - Predictive validity of the K-SADS-PL 2009 version in school-aged and adolescent
outpatients.
AB - BACKGROUND: The schedule for affective disorders and schizophrenia for school-age
children (K-SADS) is one of the most commonly used standardized diagnostic
interviews in child and adolescent psychiatry. Validity studies are scarce, and
limited to concurrent validity with other measures and clinical diagnoses. AIMS:
To evaluate the K-SADS interview in an outpatient child and adolescent psychiatry
(CAP) setting with a Longitudinal Expert All Data (LEAD) procedure. METHODS: CAP
residents performed a K-SADS-PL interview with the revised 2009 version
containing the new PDD section on 239 clinically referred outpatients of 6-17
years old and their parent(s). A consensus LEAD diagnosis by two senior
clinicians 1.2 (SD = 0.6) years later was based on clinical records including the
K-SADS and subsequent information from further assessments, information from
teachers and other informants, outcome of treatment, and at least three visits
after the K-SADS. RESULTS: Predictive validity for K-SADS vs LEAD diagnoses were
good-to-excellent for broader categories of anxiety disorders (kappa = 0.94),
depressive (kappa = 0.91), behavioural (kappa = 0.91) and tic (kappa = 0.81)
disorders, good for ADHD (kappa = 0.80), and good-to-moderate for autism spectrum
disorders (kappa = 0.62). Bipolar, psychotic, and eating disorders were too few
to be analysed. CONCLUSION: The K-SADS diagnoses elicited from an interview with
the child and one from parents on one occasion have an excellent validity for
most major child psychiatric disorders. ADHD can be reliably diagnosed at one
visit, but clinicians need to stay alert for possible undiagnosed ADHD.
Diagnosing autism with K-SADS-PL 2009 version at one visit is not advisable.
PMID- 28413936
TI - Processing speed can monitor stimulant-medication effects in adults with
attention deficit disorder with hyperactivity.
AB - BACKGROUND: Treatment responses to methylphenidate by adults with ADHD are
generally monitored against DSM-IV/DSM-V symptomatology, rating scales or
interviews during reviews. AIMS: To evaluate the use of single- and dual
dimension processing-speed and efficiency measures to monitor the effects of
pharmacological treatment with methylphenidate after a short period off
medication. METHODS: A Quick Test of Cognitive Speed (AQT) monitored the effects
of immediate-release methylphenidate in 40 previously diagnosed and medicated
adults with ADHD. Processing speed was evaluated with prior prescription
medication, without medication after a 2-day period off ADHD medication, and with
low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride
(Medikinet IR). RESULTS: Thirty-three participants responded to the experimental
treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant
main effects for single dimension colour and form and dual-dimension colour-form
naming. Post-hoc analysis indicated statistical differences between the no- and
high-dose medication conditions for colour and form, measures of perceptual
speed. For colour-form naming, a measure of cognitive speed, there was a
significant difference between no- and low-dose medication and between no- and
high-dose medications, but not between low- and high-dose medications.
CONCLUSIONS: Results indicated that the AQT tests effectively monitored
incremental effects of the methylphenidate dose on processing speed after a 2-day
period off medication. Thus, perceptual (colour and form) and cognitive speed
(two-dimensional colour-form naming) and processing efficiency (lowered shift
costs) increased measurably with high-dose medication. These preliminary findings
warrant validation with added measures of associated behavioural and cognitive
changes.
PMID- 28413937
TI - Alexithymia and depression in the recovery of chronic pain patients: a follow-up
study.
AB - BACKGROUND: Childhood adversities and emotional dysregulation are connected with
chronic pain, alexithymia, and depression. Longitudinal studies exploring the
impact of their co-occurrence on the pain situation are rare. AIMS: The influence
of alexithymia, depression, baseline pain situation, and treatment options on the
course of chronic pain in a clinical sample was studied. METHODS: The baseline
data was collected from chronic pain patients (n = 154) before their first pain
clinic visit, and the follow-up data after 1 year by self-report questionnaires.
Study variables consisted of pain intensity, pain disability, alexithymia (TAS
20), depression (BDI-II), and treatment interventions. Statistical analyses were
performed to find out differences between baseline and follow-up, as well as
between alexithymic and non-alexithymic patients, and to estimate the effect of
the treatment provided. RESULTS: At follow-up, the majority of the patients had
pain intensity and disability severe enough to disrupt with their daily living.
None of treatment interventions was related to better outcome. Alexithymic
patients reported more pain disability and depression at both baseline and at
follow-up. The effect of alexithymia on pain disability was mediated by
depression. The use of opioids was connected to alexithymia and depressiveness.
Alexithymia and depression made a substantial contribution to poorer outcome.
CONCLUSIONS: Severe pain intensity and disability with depression and alexithymia
predicted difficulties in achieving improvement. Depression and alexithymia
probably impair compliance with treatment and adherence to interventions. Their
co-occurrence with a more severe pain situation and with the use of opioids
indicates psychological problems underlying the pain experience.
PMID- 28413938
TI - Psychiatric service users' experiences of emergency departments: a CERQual review
of qualitative studies.
AB - BACKGROUND: There is increased clinical and political attention towards
integrating general and psychiatric emergency departments (ED). However, research
into psychiatric service users' experiences regarding general EDs is limited.
AIM: To identify and summarize current, qualitative evidence regarding service
users' experiences attending EDs. A secondary aim is to apply and test the newly
developed CERQual approach to summarizing qualitative review findings. METHODS: A
systematic literature review of five databases based on PRISMA guidelines yielded
3334 unique entries. Screening by title/abstract identified 57 studies and, after
full text assessment, nine studies were included. The included studies were
critically appraised using CASP. Thematic synthesis was applied for data
extraction and identification of findings. The CERQual approach was utilized to
assess the confidence of the findings. RESULTS: The results of the review showed
moderate confidence in the findings that service users experience meeting caring
and judgmental ED staff, and that waiting times and a stressful environment are
integral to their ED experiences. In contrast, low-to-very low confidence was
seen in the findings that service users experience having their symptoms ignored
and that EDs are used due to a lack of alternatives. A companion may improve
service users experience and outcome of ED visits. CONCLUSION: Service users
experience stress and discomfort in the ED. Service users highly appreciate
knowing staff who can ease the discomfort. Overall, the results of this review
speak in favour of integrated EDs where service users' needs are more likely to
be recognized and accommodated.
PMID- 28413940
TI - Elevated mRNA expression of CASPR3 in patients with schizophrenia.
AB - BACKGROUND: Recently, it was reported that antipsychotic treatment reverted
Contactin Associated Protein-Like 3 (CASPR3, same as CNTNAP3) mRNA expressions in
leukocytes of schizophrenia (SCZ) subjects to the same levels as healthy
controls. CASPR3 was expressed in various regions of the mice brain (cortex,
frontal lobes, corpus callosum, hippocampus, etc.). Thus, this study evaluated
CASPR3 mRNA expression in SCZ subjects to find a new clue of schizophrenia
pathogenesis. METHODS: One hundred SCZ subjects and 100 age-matched controls were
compared. Levels of CASPR3 mRNA in leukocytes were analysed with a quantitative
real-time PCR method using TaqMan probes. RESULTS: CASPR3 mRNA expression was
significantly higher in leukocytes of SCZ subjects than controls. However, there
were no significant correlations between expression level and any clinical
parameters in 50 SCZ subjects. CONCLUSION: Considering that CASPR3 is involved in
building the brain neural network and autophagy in circulating leukocytes,
abnormal CASPR3 expression in SCZ subjects may be associated with the
pathogenesis of SCZ.
PMID- 28413941
TI - Psychobiological Protective Factors Modifying the Association Between Age and
Sexual Health in Men: Findings From the Men's Health 40+ Study.
AB - Sexual health severely decreases with age. For males older than 40 years,
erectile dysfunction (ED) is the most common sexual disorder. Although physical
and psychological risk factors for ED have been identified, protective factors
are yet to be determined. To date, no study has examined endocrine and
psychosocial factors in parallel with regard to their modifying effect on the age
related increase in ED. Two hundred and seventy-one self-reporting healthy men
aged between 40 and 75 years provided both psychometric data on sexual function
and a set of potential psychosocial protective factors, and saliva samples for
the analysis of steroid hormones and proinflammatory cytokines. Around 35% of the
participants reported at least a mild form of ED. Direct associations with ED
were identified for perceived general health, emotional support, relationship
quality, intimacy motivation but not for steroid hormones or proinflammatory
markers. Moderation analyses for the association between age and ED revealed
positive effects for testosterone (T), dehydroepiandrosterone (DHEA), perceived
general health, emotional support, intimacy motivation, and a negative effect for
interleukin-6 (all p < .05; f2 > .17). Group differences between older men with
and without ED emerged for T, DHEA, and psychometric measures such as perceived
general health, emotional support, satisfaction with life, and intimacy
motivation (all p < .05; d > .3). Both psychosocial and endocrine parameters
moderated the association between age and sexual health. Perceived general
health, emotional support, intimacy motivation, and relationship quality emerged
as psychosocial protective factors against ED. Higher T and DHEA and lower
interleukin-6 levels also buffered against an age-related increase in ED.
PMID- 28413942
TI - Barriers to Offering Vasectomy at Publicly Funded Family Planning Organizations
in Texas.
AB - Few publicly funded family planning clinics in the United States offer vasectomy,
but little is known about the reasons this method is not more widely available at
these sources of care. Between February 2012 and February 2015, three waves of in
depth interviews were conducted with program administrators at 54 family planning
organizations in Texas. Participants described their organization's vasectomy
service model and factors that influenced how frequently vasectomy was provided.
Interview transcripts were coded and analyzed using a theme-based approach.
Service models and barriers to providing vasectomy were compared by organization
type (e.g., women's health center, public health clinic) and receipt of Title X
funding. Two thirds of organizations did not offer vasectomy on-site or pay for
referrals with family planning funding; nine organizations frequently provided
vasectomy. Organizations did not widely offer vasectomy because they could not
find providers that would accept the low reimbursement for the procedure or
because they lacked funding for men's reproductive health care. Respondents often
did not perceive men's reproductive health care as a service priority and
commented that men, especially Latinos, had limited interest in vasectomy.
Although organizations of all types reported barriers, women's health centers and
Title X-funded organizations more frequently offered vasectomy by conducting
tailored outreach to men and vasectomy providers. A combination of factors
operating at the health systems and provider level influence the availability of
vasectomy at publicly funded family planning organizations in Texas. Multilevel
approaches that address key barriers to vasectomy provision would help
organizations offer comprehensive contraceptive services.
PMID- 28413943
TI - Assessment on Occurrences of Depression and Anxiety and Associated Risk Factors
in the Infertile Chinese Men.
AB - The prevalence of depression and anxiety in the Chinese male population with
infertility is still uncertain. The prevalence of depression, anxiety, and a
combination of both psychological symptoms was 20.8%, 7.8%, and 15.4%,
respectively in 771 infertile Chinese men in the current study by the Mental
Health Inventory-5 and the State-Trait Anxiety Inventory-Short Form
questionnaires. Differences in demographics (age, education, and income) had no
noticeable impact on the development of psychological symptoms. Clinical factors
such as concomitant disorders (varicocele, epididymal cyst, and erectile
dysfunction) were identified as risk factors associated with depressive symptoms
( OR = 1.47; 95% CI [1.14, 1.90]; p < .001) and both depressive and anxiety
symptoms ( OR = 1.56; 95% CI [1.17, 2.08]; p < .001). An infertility duration
over 2 years was associated with a high risk of anxiety symptoms ( OR = 3.94; 95%
CI [1.20, 12.93], p < .02). Other clinical conditions such as type of treatment
and quality of sperm were not significant risk factors for psychological
symptoms. This study provides evidence that Chinese men of reproductive age who
suffer from infertility are vulnerable to psychological distress.
PMID- 28413944
TI - The Assessment of Motor Fatigability in Persons With Multiple Sclerosis: A
Systematic Review.
AB - BACKGROUND: Persons with multiple sclerosis (PwMS) are often characterized by
increased motor fatigability, which is a performance change on an objectively
measured criterion after any type of voluntary muscle contractions. This review
summarizes the existing literature to determine which protocols and outcome
measures are best to detect or study motor fatigability and the underlying
mechanisms in MS. METHODS: Two electronic databases, PubMed and Web of Science,
were searched for relevant articles published until August 2016 with a
combination of multiple sclerosis, fatigability, muscle fatigue, and motor
fatigue. RESULTS: A total of 48 articles were retained for data extraction. A
variety of fatigability protocols were reported; protocols showed differences in
type (isometric vs concentric), duration (15 to 180 s), and number of
contractions (fixed or until exhaustion). Also, 12 articles reported motor
fatigability during functional movements, predominantly assessed by changes in
walking speed; 11 studies evaluated the mechanisms underlying motor fatigability,
using additional electrical nerve or transcranial magnetic stimulation. Three
articles reported psychometrics of the outcomes. CONCLUSIONS: The disparity of
protocols and outcome measures to study different aspects of motor fatigability
in PwMS impedes direct comparison between data. Most protocols use maximal single
joint isometric contractions, with the advantage of high standardization. Because
there is no head-to-head comparison of the different protocols and only limited
information on psychometric properties of outcomes, there is currently no gold
standard to assess motor fatigability. The disability level, disease phenotype,
and studied limb may influence the assessment of motor fatigability in PwMS.
PMID- 28413946
TI - Kinetics of Ligand Binding Through Advanced Computational Approaches: A Review.
AB - Ligand residence times and binding rates have been found to be useful quantities
to consider during drug design. The underlying structural and dynamic
determinants of these kinetic quantities are difficult to discern. Driven by
developments in computational hardware and simulation methodologies, molecular
dynamics (MD) studies on full binding and unbinding pathways have emerged
recently, showing these structural and dynamic determinants in atomic detail.
However, the long timescales related to drug binding and release are still
prohibitive to conventional MD simulation. Here we discuss a suite of enhanced
sampling methods that have been applied to the study of full ligand binding or
unbinding pathways, and reveal the kinetics of drug binding and/or release. We
divide these sampling methods into three families (trajectory parallelization,
metadynamics, and temperature- based methods), and discuss recent applications of
each, as well as their basic theoretical underpinnings including how kinetic
information is extracted. We then present an outlook for how the field could
evolve, and how the rich variety of sampling methods discussed here can be
leveraged in the future for computationally driven drug design.
PMID- 28413945
TI - Body-Machine Interface Enables People With Cervical Spinal Cord Injury to Control
Devices With Available Body Movements: Proof of Concept.
AB - This study tested the use of a customized body-machine interface (BoMI) for
enhancing functional capabilities in persons with cervical spinal cord injury
(cSCI). The interface allows people with cSCI to operate external devices by
reorganizing their residual movements. This was a proof-of-concept phase 0
interventional nonrandomized clinical trial. Eight cSCI participants wore a
custom-made garment with motion sensors placed on the shoulders. Signals derived
from the sensors controlled a computer cursor. A standard algorithm extracted the
combinations of sensor signals that best captured each participant's capacity for
controlling a computer cursor. Participants practiced with the BoMI for 24
sessions over 12 weeks performing 3 tasks: reaching, typing, and game playing.
Learning and performance were evaluated by the evolution of movement time,
errors, smoothness, and performance metrics specific to each task. Through
practice, participants were able to reduce the movement time and the distance
from the target at the 1-second mark in the reaching task. They also made
straighter and smoother movements while reaching to different targets. All
participants became faster in the typing task and more skilled in game playing,
as the pong hit rate increased significantly with practice. The results provide
proof-of-concept for the customized BoMI as a means for people with absent or
severely impaired hand movements to control assistive devices that otherwise
would be manually operated.
PMID- 28413947
TI - Novel Signaling Interface Constituted with Membrane Receptor-Like Kinases Emerged
from the Study of Interaction and Transphosphorylation of BRI1 and BAK1.
AB - BRI1 and BAK1 are Receptor-Like Kinases (RLKs), one of the largest gene families
in plants participating in various cell signal transduction from cell surface to
cytoplasm with oligomerization and phosphorylation to regulate plant growth,
development, immunity, and environmental responses. Based on the recent
investigations on the BRI1 and BAK1 and other RLKs involving in the receptor
complex formation, transphosphorylation, phosphorylation sites identification,
downstream substrates identification, and so on, it is recovered that the
receptors oligomerization and phosphorylation integrate multiple distinct
signaling to realize signaling modulation, divergence, convergence, and
specificity. The studies of the complex formation and phosphorylation of BRI1 and
BAK1 uncovered the potential signaling transduction interface primarily composed
of the RLKs. The general novel model will be helpful to understand the plant cell
signal transduction networks.
PMID- 28413948
TI - Some Remarks on Prediction of Drug-Target Interaction with Network Models.
AB - System-level understanding of the relationships between drugs and targets is very
important for enhancing drug research, especially for drug function
repositioning. The experimental methods used to determine drug-target
interactions are usually time-consuming, tedious and expensive, and sometimes
lack reproducibility. Thus, it is highly desired to develop computational methods
for efficiently and effectively analyzing and detecting new drug-target
interaction pairs. With the explosive growth of different types of omics data,
such as genome, pharmacology, phenotypic, and other kinds of molecular networks,
numerous computational approaches have been developed to predict Drug-Target
Interactions (DTI). In this review, we make a survey on the recent advances in
predicting drug-target interaction with network-based models from the following
aspects: i) Available public data sources and benchmark datasets; ii) Drug/target
similarity metrics; iii) Network construction; iv) Common network algorithms; v)
Performance comparison of existing network-based DTI predictors.
PMID- 28413949
TI - The Intrinsic Relationship Between Structure and Function of the
Sialyltransferase ST8Sia Family Members.
AB - As a subset of glycosyltransferases, the family of sialyltransferases catalyze
transfer of sialic acid (Sia) residues to terminal non-reducing positions on
oligosaccharide chains of glycoproteins and glycolipids, utilizing CMP-Neu5Ac as
the activated sugar nucleotide donor. In the four known sialyltransferase
families (ST3Gal, ST6Gal, ST6GalNAc and ST8Sia), the ST8Sia family catalyzes
synthesis of alpha2, 8-linked sialic/polysialic acid (polySia) chains according
to their acceptor specificity. We have determined the 3D structural models of the
ST8Sia family members, designated ST8Sia I (1), II(2), IV(4), V(5), and VI(6)
using the Phyre2 server. Accuracy of these predicted models are based on the
ST8Sia III crystal structure as the calculated template. The common structural
features of these models are: (1) Their parallel templates and disulfide bonds
are buried within the enzymes and are predominately surrounded by helices; (2)
The anti-parallel beta-sheets are located at the N-terminal region of the
enzymes; (3) The mono-sialytransferases (mono-STs), ST8Sia I and ST8Sia VI,
contain only a single pair of disulfide bonds, and there are no anti-parallel
beta-sheets in ST8Sia VI; (4) The Nterminal region of all of the mono-STs are
located some distant away from their core structure; (5) These conformational
features show that the 3D structures of the mono-STs are less compact than the
two polySTs, ST8Sia II and ST8Sia IV, and the oligo-ST, ST8Sia III. These
structural features relate to the catalytic specificity of the monoSTs; (6) In
contrast, the more compact structural features of ST8Sia II, ST8Sia IV and ST8Sia
III relate to their ability to catalyze the processive synthesis of oligo-
(ST8Sia III) and polySia chains (ST8Sia II & ST8Sia IV); (7) Although ST8Sia II,
III and IV have similar conformations in their corresponding
polysialyltransferase domain (PSTD) and polybasic region (PBR) motifs, the
structure of ST8Sia III is less compact than ST8Sia II and ST8Sia IV, and the
amino acid components of the several three-residue-loops in the two motifs of
ST8Sia III are different from that in ST8Sia II and ST8Sia IV. This is likely the
structural basis for why ST8Sia III is an oligoST and not able to polysialylate
and; (8) In contrast, essentially all amino acids within the threeresidue- loops
in the PSTD of ST8Sia II and ST8Sia IV are highly conserved, and many amino acids
in the loops and the helices of these two motifs are critical for NCAM
polysialylation, as determined by mutational analysis and confirmed by our recent
NMR results. In summary, these new findings provide further insights into the
molecular mechanisms underlying polyST-NCAM recognition, polySTpolySia/ oligoSia
interactions, and polysialylation of NCAM.
PMID- 28413950
TI - A Critical Review of Validation, Blind Testing, and Real- World Use of Alchemical
Protein-Ligand Binding Free Energy Calculations.
AB - Protein-ligand binding is among the most fundamental phenomena underlying all
molecular biology, and a greater ability to more accurately and robustly predict
the binding free energy of a small molecule ligand for its cognate protein is
expected to have vast consequences for improving the efficiency of pharmaceutical
drug discovery. We briefly reviewed a number of scientific and technical advances
that have enabled alchemical free energy calculations to recently emerge as a
preferred approach, and critically considered proper validation and effective use
of these techniques. In particular, we characterized a selection bias effect
which may be important in prospective free energy calculations, and introduced a
strategy to improve the accuracy of the free energy predictions.
PMID- 28413951
TI - An Unprecedented Revolution in Medicinal Chemistry Driven by the Progress of
Biological Science.
AB - The eternal or ultimate goal of medicinal chemistry is to find most effective
ways to treat various diseases and extend human beings' life as long as possible.
Human being is a biological entity. To realize such an ultimate goal, the inputs
or breakthroughs from the advances in biological science are no doubt most
important that may even drive medicinal science into a revolution. In this review
article, we are to address this from several different angles.
PMID- 28413952
TI - Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where
Molecular Modeling Meets Systems Biology.
AB - Cellular drug targets exist within networked function-generating systems whose
constituent molecular species undergo dynamic interdependent non-equilibrium
state transitions in response to specific perturbations (i.e.. inputs). Cellular
phenotypic behaviors are manifested through the integrated behaviors of such
networks. However, in vitro data are frequently measured and/or interpreted with
empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs
Haldane) relevant to isolated target populations. We propose that cells act as
analog computers, "solving" sets of coupled "molecular differential equations"
(i.e. represented by populations of interacting species)via "integration" of the
dynamic state probability distributions among those populations. Disconnects
between biochemical and functional/phenotypic assays (cellular/in vivo) may arise
with targetcontaining systems that operate far from equilibrium, and/or when
coupled contributions (including target-cognate partner binding and drug
pharmacokinetics) are neglected in the analysis of biochemical results. The
transformation of drug discovery from a trial-and-error endeavor to one based on
reliable design criteria depends on improved understanding of the dynamic
mechanisms powering cellular function/dysfunction at the systems level. Here, we
address the general mechanisms of molecular and cellular function and
pharmacological modulation thereof. We outline a first principles theory on the
mechanisms by which free energy is stored and transduced into biological
function, and by which biological function is modulated by drug-target binding.
We propose that cellular function depends on dynamic counter-balanced molecular
systems necessitated by the exponential behavior of molecular state transitions
under non-equilibrium conditions, including positive versus negative mass action
kinetics and solute-induced perturbations to the hydrogen bonds of solvating
water versus kT.
PMID- 28413953
TI - Calculating Water Thermodynamics in the Binding Site of Proteins - Applications
of WaterMap to Drug Discovery.
AB - The ability to accurately characterize the solvation properties (water locations
and thermodynamics) of biomolecules is of great importance to drug discovery.
While crystallography, NMR, and other experimental techniques can assist in
determining the structure of water networks in proteins and protein-ligand
complexes, most water molecules are not fully resolved and accurately placed.
Furthermore, understanding the energetic effects of solvation and desolvation on
binding requires an analysis of the thermodynamic properties of solvent involved
in the interaction between ligands and proteins. WaterMap is a molecular dynamics
based computational method that uses statistical mechanics to describe the
thermodynamic properties (entropy, enthalpy, and free energy) of water molecules
at the surface of proteins. This method can be used to assess the solvent
contributions to ligand binding affinity and to guide lead optimization. In this
review, we provide a comprehensive summary of published uses of WaterMap,
including applications to lead optimization, virtual screening, selectivity
analysis, ligand pose prediction, and druggability assessment.
PMID- 28413954
TI - Computational Models for Understanding of Structure, Function and Pharmacology of
the Cardiac Potassium Channel Kv11.1 (hERG).
AB - The rapid delayed rectifier current IKr is one of the major K+ currents involved
in repolarization of the human cardiac action potential. Various inherited or
drug-induced forms of the long QT syndrome (LQTS) in humans are linked to
functional and structural modifications in the IKr conducting channels. IKr is
carried by the potassium channel Kv11.1 encoded by the gene KCNH2 (commonly
referred to as human ether-a-go-go-related gene or hERG) [1, 2]. The first
necessary step for predicting emergent drug effects on the heart is determining
and modeling the binding thermodynamics and kinetics of primary and major off
target drug interactions with subcellular targets. The bulk of drugs that target
hERG channels are known to have complex interactions at the atomic scale.
Accordingly, one of the goals for this review is to provide comprehensive guide
in the universe of computational models aiming to refine our understanding of
structure-function relations in Kv11.1 and its isoforms. The special emphasis is
placed on the mapping of drug binding sites and tentative mechanisms of channel
inhibition and activation by drugs. An overview over recent structural models and
mapping of binding sites for blockers and activators of IKr current along with
the discussion on agreements and discrepancies among different models is
presented. There is an apparent reciprocity or feedback loop between drug binding
and action potential of the cardiac myocytes. Thus one has to connect drug
binding to a particular receptor so that its functional consequences impact on
the action potential duration. The natural pathway is to develop multi-scale
models that connect between receptor and cellular scales. The potential for such
multi-scale model development is discussed through the lens of common gating
models. Accordingly, the second part of this review covers an ongoing development
of the kinetic models of gating transitions and cardiac ion currents carried by
hERG channels with and without drug bound.
PMID- 28413955
TI - Drug Discovery and Molecular Dynamics: Methods, Applications and Perspective
Beyond the Second Timescale.
AB - Bio-molecular dynamics (MD) simulations based on graphical processing units
(GPUs) were first released to the public in the early 2009 with the code ACEMD.
Almost 8 years after, applications now encompass a broad range of molecular
studies, while throughput improvements have opened the way to millisecond
sampling timescales. Based on an extrapolation of the amount of sampling in
published literature, the second timescale will be reached by the year 2022, and
therefore we predict that molecular dynamics is going to become one of the main
tools in drug discovery in both academia and industry. Here, we review successful
applications in the drug discovery domain developed over these recent years of
GPU-based MD. We also retrospectively analyse limitations that have been overcome
over the years and give a perspective on challenges that remain to be addressed.
PMID- 28413956
TI - Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin.
AB - BACKGROUND: Haspin (haploid germ cell-specific nuclear protein kinase) is an
atypical serine/threonine-protein kinase that was for a long time considered an
inactive pseudokinase due to low degree of structural homology of Haspin with the
'classical' protein kinases. However, the discovery of Haspin-catalyzed
phosphorylation of histone H3 at Thr3 residue unveiled importance of Haspin in
mitosis and provided yet another link between mitotic phosphorylation pathways
and chromatin modifications. RESULTS: In this review of 111 publications, we have
(1) briefly summarized catalytic properties and physiological roles of Haspin,
(2) focussed on the architecture of Haspin and mechanisms behind its substrate
recognition, (3) provided detailed insight into the advances in the development
and characterization of Haspin-selective inhibitors, and (4) given overview of
inhibitor scaffolds that despite targeting other protein kinases feature Haspin
as a common off-target. CONCLUSION: The chemical space of Haspin-targeting low
molecular-weight-compounds has not yet been widely explored, but several
scaffolds (e.g., derivatives of acridine, beta-carboline or 5-iodotubercidin)
have emerged as promising inhibitors. The inclusion of Haspin into protein kinase
panels for profiling of low-molecular-weight-compounds in several recent studies
has provided valuable information about the structure-affinity or structure
activity relationship of well-known or novel inhibitors towards Haspin.
PMID- 28413957
TI - Sulfur Containing Acridine Derivatives in Preclinical Studies with Cancer Cell
Lines.
AB - BACKGROUND: The possible use of acridines as anticancer agents was first
considered in the 1920's. Since then, a large number of acridine drugs have been
tested as antitumour agents, including compounds containing sulphur on the
acridine chromophore. In this review, we will discuss recent studies which have
investigated the anticancer activity of this class of acridine derivatives.
METHODS: We present the results both of our own decade-long research and also of
existing research literature into the anticancer activity of acridine derivatives
containing sulphur. The evidence of specific tumor-cell killing properties
displayed by these compounds suggest the potential of using such molecules as
anticancer therapeutics. RESULTS: During the last decade, a number of acridine
analogs have been developed by modifying the position and the nature of the
substituent on the acridine core. In this paper, we published results on the
anticancer activity of acridine derivatives containing sulfur (acridine
thioureas, acridine thiazolidine/thiazoidinone, and acridine thiosemicarbazones/
thiosemicarbazides). In cancer chemotherapy, the mechanism of the drugs is
complex, although the study of the anticancer activity of acridines has yielded
exciting results. CONCLUSION: In this review we have summarized recent literature
on the anticancer activity of acridine derivatives containing sulfur. A
considerable amount of published data suggests that these compounds exhibit
promising anticancer activity against selected cancer cell lines. The obtained
results can be helpful in the development of new pharmaceutical agents.
PMID- 28413958
TI - Anti-fatigue effects of active ingredients from traditional Chinese medicine: a
review.
AB - Fatigue, a phenomenon which is believed to be caused by body exercise, can lead
to the failure of predetermined exercise intensity maintenance and sport ability
declination. The usage of traditional Chinese medicine (TCM) in the treatment of
fatigue has long been practiced in clinical and showed significant effects. This
article covers related literatures in recent years and sorts the effective
ingredients from TCM for treating fatigue into a few categories including
alkaloids, saponins, polysaccharides, polyphenols, polypeptide, terpene, proteins
and other active ingredients. Research status, sources, models, efficacy and
mechanisms of active ingredients and their monomer in the treatment of fatigue
are discussed. Pharmacological research shows that active ingredients of
polysaccharide can significantly improve body's resistance through promoting
glycogen synthesis, reducing sports metabolites and increasing hypoxia tolerance;
Alkaloids has been proved to be effective in promoting the reserving of various
glucogen substances, improving exercise endurance and speeding up the metabolism
of body's urea nitrogen in mice; With the increase of glycosides amount, up goes
the sport endurance, liver glycogen content and the ability of clear lactate
index in mice, indicating that saponin has clear, dose-dependent anti-fatigue
effect; Polyphenols also have functions of resisting fatigue, where they reduce
free radicals accumulated and thus slow down the rapid declination of exercise
capacity when doing sports; There are other active ingredients of TCM that have
biological activities, like some proteins, anthraquinones, terpenes, unsaturated
fatty acid monomer compounds; And research has found that tonic medicine can
promote the elimination of fatigue and improve athletic ability.
PMID- 28413959
TI - Chemopreventive Properties of Tolfenamic Acid: A Mechanistic Review.
AB - Tolfenamic acid is one of the conventional non-steroidal anti-inflammatory drugs
(NSAIDs) commonly used for the treatment of inflammation, migraines and pain.
There has been a growing body of experimental evidence that tolfenamic acid
possesses anti-cancer activity. However, in order to develop a therapeutic
strategy using tolfenamic acid for the treatment of cancer, further research is
required to highlight reliable cellular and molecular mechanisms of anti-cancer
properties. Tolfenamic acid has been shown to alter the expression of several
genes that represent cancer hallmarks including apoptosis, growth arrest,
angiogenesis and metastasis. Recently, a couple of research groups including ours
reported that tolfenamic acid targets multiple oncogenic or tumor suppressive
signaling pathways in various types of cancer models. Here, we highlight multiple
molecular targets responsible for the anti-cancer mechanism of tolfenamic acid
and the benefits of combinational use of this drug with other anti-cancer drugs.
PMID- 28413960
TI - Circulating ACE2 in Cardiovascular and Kidney Diseases.
AB - Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the
conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti
fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2
counterbalances the effects of Ang II, it has been proposed as a biomarker in
kidney disease patients. Circulating ACE2 has been studied in human and
experimental studies under physiological and pathological conditions and
different techniques have been assessed to determine its enzymatic activity. In
patients with cardiovascular (CV) disease circulating ACE2 has been shown to be
increased. In addition, hypertensive and diabetic patients have also shown higher
circulating ACE2 activities. A study in type 1 diabetes patients found a negative
association between circulating ACE2 and estimated glomerular filtration rate in
male and female patients. Recently, it has been demonstrated that circulating
ACE2 is increased in male patients with chronic kidney disease (CKD) and that it
is independently associated with other classical CV risk factors, such as
advanced age and diabetes. Furthermore, circulating ACE2 has been shown to be
associated with silent atherosclerosis and CV outcomes in CKD patients. In
diabetic nephropathy, experimental studies have demonstrated an increase in
circulating ACE2 activity both at early and late stages of the disease, as well
as a direct association with increased urinary albumin excretion, suggesting that
it may be increased as a renoprotective mechanism in these patients. In this
paper we will review the measurement of circulating ACE2 and its role in kidney
disease, as well as its potential role as a renal and CV biomarker.
PMID- 28413961
TI - Incretins and Lipid Metabolism.
AB - BACKGROUND: Recent findings indicate that incretin hormones and incretin-based
therapies may affect the metabolism of lipoproteins, although the corresponding
mechanisms are not clearly defined. OBJECTIVE: To summarize the available data on
the mechanisms linking incretins with the characteristics of serum lipoproteins
and discuss the clinical implications of these relationships. METHODS: PubMed was
searched using the terms "incretins", "GLP-1", "GIP" and "lipids",
"dyslipidemia", "triglycerides", "apolipoprotein B48". All articles published in
the English language until June 2016 were assessed and the relevant information
is presented here. RESULTS: GLP-1, and therapies that increase its activity,
exert a beneficial effect on lipoprotein metabolism that is translated in a
reduction in the fasting and postprandial concentration of triglycerides and a
small improvement in the concentration and function of HDLs. In addition, a shift
towards larger, less atherogenic particles usually follows the administration of
GLP-1 receptor agonists. The mechanisms that underlie these changes involve a
direct effect of GLP- 1 on the hepatic and intestinal production of triglyceride
rich lipoproteins, the GLP-1 induced increase in the production and function of
insulin, the activation of specific areas of central nervous system as well as
the increase in the peripheral utilization of triglycerides for energy
production. On the other hand, GLP-2 increases the absorption of dietary fat and
the production of triglyceride-rich lipoproteins while the role of GIP on lipid
metabolism remains indeterminate. CONCLUSION: GLP-1 and incretin-based therapies
favorably affect lipid metabolism. These effects may contribute to the beneficial
effects of incretin-based therapies on atherosclerosis and fatty liver disease.
PMID- 28413963
TI - Overview of Cantharidin and its Analogues.
AB - BACKGROUND: Cantharidin has been categorized as highly toxicant in Chinese
medicine. But cantharidin can efficiently treat different types of diseases, such
as molluscum contagiosum. While cantharidin is quite useful, unfortunately, due
to its side effects, increasing regulations have limited access to this useful
therapeutic option. Cantharidin's toxic effects have caused it to fall into
disuse for most legitimate medical purposes. Although cantharidin generates
effects and its advantages must be realized. Recently, cancer affects people's
life more and more. Because cantharidin can treat some cancers, so solutions must
be used to reduce side effects. This review aims to describe some its analogues,
several efficient methods to inhibit the side effects of cantharidin and
pharmacogenomics of cantharidin. METHODS: We searched for research about
cantharidin by entering the database. Then evaluated these papers and analyzed
their founding, solution, mechanism, etc., and targeted to screen the papers
related to the content of our research, and then sorted them out in accordance
with the solution, mechanism research and other content. Finally, these content
was unified into a framework. RESULTS: Some cantharidin's analogues were found
that they show some similar functions to cantharidin and we found that
norcantharidin, acylthiourea derivatives, cantharidinamides, anhydride-modified
derivatives and other derivatives have less side effects. The modified
cantharidin analogues reduce toxicity in hepatocytes. Cantharidin consists of a
six-ring and a five-ring, the moiety of oxygen on the six-ring and the anhydride
section exhibit biochemical activity. Protein phosphatases are associated with
many cellular processes including apoptosis, cell cycle progression and so on.
Cantharidin can cause apoptosis and double-stand breakage of DNA. Cantharidin and
norcantharidin can efficiently inhibit the activity of mammalian and plant
protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) in vivo.
Cantharidin inhibits PP5 at the nanomolar level with an IC50 value of 600 nM. PP5
can manage the cellular survival, death, proliferation and other some
intracellular biological activities in mammals. After cantharidin's treatment,
the level of EtPP5 mRNA expression was downregulated. Their also can be used to
inhibit the Glutathione S-transferases (GSTs), angiogenesis and the expression of
A549 human lung cancer cells, trigger eryptosis and induced bladder cancer cell
apoptosis. We found that using Vitamin C and ginsenosides and translating
cantharidin into nanoparticles can minimize the cantharidin side effects in the
patients. CONCLUSION: Cantharidin can inhibit various tumor cell lines.
Cantharidin causes both DNA single- and double- strand breaks and induces
apoptosis. Although cantharidin shows some toxicity for human, its anti-cancer
effects should be taken seriously. Several viable methods can help solve this
problem. The most important pharmacogenomics of cantharidin is that cantharidin
can inhibit PPs, because PPs are associated with many cellular processes. This
prospect is very broad and needs to continue studying.
PMID- 28413964
TI - Sex-Genetic Interaction in the Risk for Cerebrovascular Disease.
AB - Cerebrovascular disease (CeVD) is one of the major causes of death and a leading
cause of disability worldwide. CeVD is a complex and multifactorial disease
caused by the interaction of environment and genetic factors. Women have lower
CeVD incidence than men until an advanced age, when the incidence of CeVD rises
dramatically in women. Therefore, sex has been validated as an important risk
factor in the etiology of CeVD, especially ischemic stroke. Although the
importance of sex steroids have been heavily studied in the mechanism of neuronal
injury, the experimental and clinical data suggest that hormones do not fully
account for male versus female CeVD patterns. Sex-specific genetic processes have
been implicated in the different rate of risk for atherosclerosis and CeVD. In
this review, we discuss sex-specific CeVD processes, describe the hormonal impact
on the risk for CeVD, the results from studies in transgenic animals, and from
human genetic studies. Moreover, heritability of ischemic stroke in women and men
as well as identification of possible sex-specific biomarkers for CeVD are
discussed. Understanding the complex interactions between hormonal and genetic
mechanisms in the CeVD risk will allow for new sex-specific approaches in disease
treatment and prevention in clinical practice.
PMID- 28413965
TI - Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and
Future Directions.
AB - Malignant melanoma is the most aggressive and life-threatening skin cancer.
Melanoma develops in melanocytes and is characterized by a very high tendency to
spread to other parts of the body. Its pathogenesis depends on DNA mutations
leading to the activation of oncogenes or to the inactivation of suppressor
genes. The identification of misregulations in intracellular signal transduction
pathways has provided an opportunity for the development of mutation-specific
inhibitors, which specifically target the mutated signaling cascades. Over the
last few years, clinical trials with MAPK pathway inhibitors have shown
significant clinical activity in melanoma; however, their efficacy is limited due
to the onset of acquired resistance. This has prompted a large set of preclinical
studies looking at new approaches of pathway- or target-specific inhibitors. This
review gives an overview of the latest developments of small molecule targeting
multiple molecular pathways in both preclinical and clinical melanoma settings,
with particular emphasis on additional strategies to tackle the reduced
responsiveness to inhibitor treatment as possible future directions.
PMID- 28413966
TI - The Clinical Problems of Hypertension Treatment in Hemodialysis Patients.
AB - Hypertension (HT) is present in more than 80% of patients undergoing Hemodialysis
(HD). Elevated Blood Pressure (BP) in hemodialysis patients is associated with
cardiovascular events and mortality only when BP is recorded with home or
ambulatory monitoring, since pre- and post-dialysis measurements are not valid
estimates of BP levels during the interdialytic interval. Sodium and water
overload is the most important of several mechanisms involved in HT development
in HD. In this context, non-pharmacologic measures to ensure water and sodium
balance by achieving patient dry weight and decreasing daily sodium intake,
through modification of sodium level in the diet or in dialysis dialysate, are
fundamental for HT control. After these strategies are properly implemented, the
introduction of drug treatment can further help in achieving optimum BP. All
major antihypertensive classes, with the exception of diuretics, can be
considered in HT management, as current evidence suggest that the use of agents
from these classes was associated with reduced cardiovascular risk. The choice of
a specific antihypertensive drug should be based on the co-morbid conditions of
the patient, and the pharmacologic characteristics of the agent, including
dialyzability. Of note, the need of increasing the number of antihypertensive
drugs, should be each time balanced against reappraisal of the non-pharmacologic
measures, as increased antihypertensive efficacy can result in a vicious circle
of more difficulties regarding dry weight reduction, possible volume overload,
and further BP increase.
PMID- 28413962
TI - Neurochemical Markers in the Mammalian Brain: Structure, Roles in Synaptic
Communication, and Pharmacological Relevance.
AB - BACKGROUND: Knowledge of molecular marker (typically protein or mRNA) expression
in neural systems can provide insight to the chemical blueprint of signal
processing and transmission, assist in tracking developmental or pathological
progressions, and yield key information regarding potential medicinal targets.
These markers are particularly relevant in the mammalian brain in the light of
its unsurpassed cellular diversity. Accordingly, molecular expression profiling
is rapidly becoming a major approach to classify neuron types. Despite a
profusion of research, however, the biological functions of molecular markers
commonly used to distinguish neuron types remain incompletely understood.
Furthermore, most molecular markers of mammalian neuron types are also present in
other organs, therefore complicating considerations of their potential
pharmacological interactions. OBJECTIVE: Here, we survey 15 prominent
neurochemical markers from five categories, namely membrane transporters, calcium
binding proteins, neuropeptides, receptors, and extracellular matrix proteins,
explaining their relation and relevance to synaptic communication. METHOD: For
each marker, we summarize fundamental structural features, cellular
functionality, distributions within and outside the brain, as well as known drug
effectors and mechanisms of action. CONCLUSION: This essential primer thus links
together the cellular complexity of the brain, the chemical properties of key
molecular players in neurotransmission, and possible biomedical opportunities.
PMID- 28413967
TI - Uncontrolled Hypertension and Oncology: Clinical Tips.
AB - INTRODUCTION: Angiogenesis is fundamental for tumour development and progression.
Thus, anti-angiogenic agents have been developed and are mainly vascular
endothelial growth factor (VEGF) pathway inhibitors. However, these agents
commonly exhibit cardiac and renal toxicity, proteinuria and hypertension (HT).
In fact, with the use of anti-angiogenic agents a rapid dose-dependent increase
of blood pressure (BP) is observed. The possible mechanisms of VEGF inhibitors
induced HT include systemic endothelial dysfunction, renal impairment as well as
vascular micro- and macroangiopathy. Furthermore, the simultaneous use of non
steroidal anti-inflammatory drugs (NSAIDs) and opioids in these patients results
in uncontrolled HT. CONCLUSION: Lifestyle changes are the cornerstone of
antihypertensive treatment. No clear recommendations for a specific
antihypertensive agent can be made. In most cases antihypertensive management
needs to be individualized to each patient. Calcium channel blockers (CCBs) are
considered as first line option, while renin-angiotensin-aldosterone system
(RAAS) blockers should be the agents of choice in patients with proteinuria.
Centrally acting antihypertensive agents and diuretics can also be used. Careful
monitoring is critical during therapy and BP should be assessed every week and
before any new cycle or infusion of anti-VEGF therapy. If BP remains uncontrolled
anti-VEGF treatment discontinuation should be considered. Withdrawal of anti-VEGF
therapy needs also a re-evaluation of antihypertensive therapy since BP will
return to the prior baseline levels.
PMID- 28413968
TI - Hypertension and Heart Failure with Preserved Ejection Fraction: Connecting the
Dots.
AB - INTRODUCTION: Heart failure (HF) with preserved ejection fraction (EF) (HFpEF)
accounts for approximately 50% of HF cases and its prevalence relative to HF with
reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF
patients and it is implicated in both the pathogenesis and the prognosis of the
disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We
reviewed the literature for epidemiologic data supporting the co-aggregation of
the two entities as well as patho-physiologic mechanisms linking HT to HFpEF.
Most importantly, we focused on treatment options targeting HT as a preventive
strategy for delaying the progression of diastolic dysfunction or decreasing the
odds for developing HFpEF. CONCLUSION: Along this line, we summarized the
evidence and efficacy associated with different classes of antihypertensive
medications in HFpEF patients. Finally, non-pharmacological approaches, including
renal denervation and lifestyle modifications, to achieve optimal blood pressure
(BP) control in HFpEF patients are reported. Unfortunately, no specific
antihypertensive treatment has established a major survival benefit in this high
risk subjects. Until the results of the efficacy of the novel drug LCZ696
(valsartan/ sacubitril) are available, the continuous monitoring and lowering of
the BP by pharmacological and non-pharmacological means should be considered the
major preventive and treatment strategy in HFpEF patients.
PMID- 28413970
TI - Optimizing the Management of Uncontrolled/Resistant Hypertension. The Importance
of Sleep Apnoea Syndrome.
AB - INTRODUCTION: Obstructive Sleep Apnoea (OSA) constitutes the most prevalent form
of abnormal respiratory control during sleep in adults. Evidence linked OSA to
cardiovascular disease, and the role of OSA in abnormal Blood Pressure (BP)
control has been extensively studied. Although longitudinal trials suggest a
causative role of OSA in the development of hypertension, the evidence is not
fully consistent. Nasal continuous positive airway pressure (nCPAP) applied
during sleep is well documented and a highly efficient therapeutic aid to
eliminate OSA. It has been repeatedly shown that nCPAP-therapy is also associated
with modest BP lowering effect in hypertensive OSA-patients, and the magnitude of
the observed effect correlates with the severity of OSA. However, it is unlikely
that nCPAP would normalize BP. CONCLUSION: There are few studies which tested the
interplay between OSA, nCPAP and certain BPlowering drug classes. Angiotensin
receptor blockers may show synergistic hypotensive effect with nCPAP, whereas
mineralocorticoid receptor blocker has been shown to modestly attenuate the
severity of OSA. Additionally, the application of chronotherapy may be of special
use in such patients. The current evidence is sufficient to promote persistent
and effective nCPAP-therapy as a standard in all eligible OSA-patients with
difficult-to-control hypertension.
PMID- 28413969
TI - Optimizing the Management of Uncontrolled Hypertension: What do Triple Fixed-Dose
Drug Combinations Add?
AB - Fixed-dose triple drug combinations represent one of the latest innovations of
pharmacotherapy for hypertension (HT). They combine a traditional renin
angiotensin system blocker, a diuretic and a calcium channel blocker. The main
benefit is the simplification of treatment regimen because 3 different agents are
combined at different doses in a single pill. Improving adherence to treatment
partly explains why this kind of combination may effectively reduce blood
pressure (BP). BP lowering by a single- pill triple-drug combination can be
approximately predicted, by using appropriate formulas described in previous meta
analysis of randomized trials. Thus, clinicians may select the appropriate dose
for each of the combined drugs. Selection of different types of fixed-dose triple
drug combinations relies upon clinical experience, commercial availability and
evidence from clinical trials and metaanalyses for each agent alone. However,
triple fixed-dose drug combinations should be reserved only for patients with
uncontrolled BP with 2 agents, poor adherence in complex therapeutic regimens or
on inappropriate free-drug combinations. Also, triple therapy may help overcome
clinical inertia by prescribing more potent antihypertensive formulations in one
pill. In contrast, this type of multiple-drug fixed-dose combination might be
less safe in very old and frail patients, as well as in those with chronic kidney
disease. Although new combinations may help overcome the clinical inertia of
achieving individualized BP targets, doctors should also pay attention
reinforcement of lifestyle changes.
PMID- 28413971
TI - Structure of C-terminal Domain of Peptidyl-prolyl cis-trans Isomerase from
Pseudomonas syringae pv. Tomato str. DC3000 at 1.6A Resolution.
AB - BACKGROUND: Peptidyl-prolyl cis-trans isomerase (PPIase) accelerates the
intrinsically slow conversion between cis- and trans- configurations of proline,
thus affecting backbone conformation and altering the direction of peptide
chains. PPIase from Pseudomonas syringae pv. Tomato (PSPTO) DC3000 (PSPTO-PPIase)
is considered to belong to the FKBP subfamily of PPIase. OBJECTIVE: To solve the
high resolution structure of the PSPTO-PPIase, and to explore its potential
function in plants pathogen PSPTO DC3000. METHOD: The PSPTO-PPIase was expressed
in E.coli and purified through ion exchange and size exclusion chromatography.
While only the C-terminal domain of PSPTO-PPIase was successfully crystalized,
and its structure was solved to 1.6 A resolution by molecular replacement method.
RESULTS: Structural comparison showed that PSPTO-PPIase adopts a similar overall
fold with microphage infectivity potentiators (MIPs), which also belong to the
FKBP subfamily of PPIase. In addition, the BIAcore result confirmed that PSPTO
PPIase can bind an immunosuppressive drug FK506 as some other FKBP subfamily
members do. CONCLUSION: Our results suggested that PSPTO-PPIase may function in a
similar manner to virulent factor MIPs during pathogenesis. And the
immunosuppressive drugs FK506 and rapamycin binding to PSPTO-PPIase potentially
interferes and inhibits the plant pathogen PSPTO DC3000. In addition, the amino
acids with short side chains in the fourth loop (L4) of PSPTO-PPIase may account
for its variable roles in the respective pathogen.
PMID- 28413972
TI - Xanthine Oxidase and its Role as Target in Cardiovascular Disease: Cardiovascular
Protection by Enzyme Inhibition?
AB - BACKGROUND: Formerly, hyperuricemia was mainly restricted to the rich population,
but now-a-days it is a condition affecting wide parts of western civilization.
Although only a minority of our population develops clinically relevant
symptomatic hyperuricemia, there is growing evidence that elevated serum uric
acid levels might be associated with elevated cardiovascular risk and
cardiovascular disease progression. But it is not clear whether uric acid is just
a biomarker or exerts detrimental effects itself. The xanthine oxidoreductase
(XOR) is an essential enzyme for the generation of uric acid. A typical
pharmacological therapy to reduce the uric acid amounts is inhibition of XOR.
There is good evidence that inhibition of uric acid reduces cardiovascular events
in patients. The question arises if XOR inhibition might be an attractive target
to reduce cardiovascular events in patients with high or even normal uric acid
levels. METHOD: This review summarizes the available publications on the
relationship between XOR and cardiovascular co-morbidities. RESULTS: The
association of elevated serum uric acid level with oxidative damage in the vessel
wall, inflammatory and proliferative vascular changes, hypertension and impaired
kidney function are depicted. In addition, the therapeutics currently approved
for the treatments of hyperuricemia are outlined and an overview regarding novel,
currently researched XOR inhibitors is provided. CONCLUSION: Observational and
small prospective studies already have given hints for positive cardiovascular
effects of XOR inhibition. However, larger prospective studies investigating
cardiovascular outcomes are awaited to validate the potential beneficial effect
of XOR inhibition for reduction of the cardiovascular burden.
PMID- 28413973
TI - Docking-Related Survey on Natural-Product-Based New Monoamine Oxidase Inhibitors
and Their Therapeutic Potential.
AB - BACKGROUND: This is an exciting period for research on monoamine oxidase and its
effects on central nervous system. As the current hitting-one-target, therapeutic
strategy has become quite inefficient for the treatment of various neurological
disorders Objective: The objective of this review is to identify and critically
discuss the computational development of multi-target natural and related ligand
MAO protein docking approaches in the study of monoamine oxidase (MAO) enzymes.
DISCUSSION: Computational development of the new compounds from natural and
related synthetic origin, active as MAO inhibitors (MAOIs) was discussed in some
detail. The docking studies related to the alkaloids and their various categories
secondary metabolites from plants like alkaloids, flavonoids and xanthones class
of compounds specially caffeine, beta-carboline, naphthoquinone, morpholine,
piperine, amphetamine and furthermore curcumin, eugenol, trans-Farnesol and many
other extracted plant constituents with their docking studies were discussed in
detail. CONCLUSION: It is apparent that, by this computational docking approach,
more selective, reversible and potent molecules could be proposed as MAO
inhibitors by precise modifications on the basic scaffold.
PMID- 28413974
TI - Identification of Cell Cycle-Regulated Genes by Convolutional Neural Network.
AB - BACKGROUND: The cell cycle-regulated genes express periodically with the cell
cycle stages, and the identification and study of these genes can provide a deep
understanding of the cell cycle process. Large false positives and low overlaps
are big problems in cell cycle-regulated gene detection. METHODS: Here, a
computational framework called DLGene was proposed for cell cycle-regulated gene
detection. It is based on the convolutional neural network, a deep learning
algorithm representing raw form of data pattern without assumption of their
distribution. First, the expression data was transformed to categorical state
data to denote the changing state of gene expression, and four different
expression patterns were revealed for the reported cell cycle-regulated genes.
Then, DLGene was applied to discriminate the non-cell cycle gene and the four
subtypes of cell cycle genes. Its performances were compared with six traditional
machine learning methods. At last, the biological functions of representative
cell cycle genes for each subtype are analyzed. RESULTS: Our method showed better
and more balanced performance of sensitivity and specificity comparing to other
machine learning algorithms. The cell cycle genes had very different expression
pattern with non-cell cycle genes and among the cell-cycle genes, there were four
subtypes. Our method not only detects the cell cycle genes, but also describes
its expression pattern, such as when its highest expression level is reached and
how it changes with time. For each type, we analyzed the biological functions of
the representative genes and such results provided novel insight to the cell
cycle mechanisms.
PMID- 28413975
TI - The Safety of Ovarian Preservation in Stage I Endometrial Endometrioid
Adenocarcinoma Based on Propensity Score Matching.
AB - BACKGROUND: Most patients with early stage endometrial endometrioid
adenocarcinoma (EEAC) are treated with hysterectomy and bilateral oophorectomy.
But this surgical menopause leads to long-term sequelae for premenopausal women,
especially for young women of childbearing age. This population-based study was
to evaluate the safety of ovarian preservation in young women with stage I EEAC.
METHODS: Patients of age 50 or younger with stage I EEAC were explored from the
Surveillance, Epidemiology and End Results program database during 2004 to 2013.
Propensity score matching was used to randomize the data set and reduce the
selection biases of doctors. Univariate analysis and multivariate cox
proportional hazards model were utilized to estimate the safety of ovarian
preservation. RESULTS: A total of 7183 patients were identified, and ovarian
preservation was performed in 863 (12 %) patients. Compared with women treated
with oophorectomy, patients with ovarian preservation significantly tend to be
younger at diagnosis (P-value < 0.001) and more likely diagnosed as stage IA
EEAC, to have better differentiated tumor tissues and smaller tumors, as well as
less likely to undergo radiation and lymphadenectomy. 863 patients treated with
oophorectomy were selected by propensity score matching. After propensity score
matching, the differences of all characteristics between ovarian preservation and
oophorectomy were not significant and potential confounders in the two groups
decreased. In univariate analysis of matched population, ovarian preservation had
no effect on overall (P-value=0.928) and cancer-specific (P-value=0.390)
mortality. In propensityadjusted multivariate analysis, ovarian preservation was
not significantly associated with overall (HR=0.69, 95%CI=0.41-1.68, P
value=0.611) and cancer-specific (HR=1.65, 95%CI=0.54-5.06, Pvalue= 0.379)
survival. CONCLUSION: Ovarian preservation is safe for young women with stage I
EEAC, which is not significantly associated with overall and cancer-specific
mortality.
PMID- 28413977
TI - New Suggestions in Sublingual Immunotherapy for House Dust Mite- Related Allergic
Diseases.
AB - BACKGROUND: The indications for Allergen immunotherapy (AIT) in patients
suffering from House Dust Mite (HDM)-related allergic diseases are presently
based on incomplete data. This is essentially based on the fact that HDM allergy
is difficult to evaluate in clinical trials, due to the largely variable allergen
exposure and symptoms, and to the long periods of observation needed to assess
the effects. In addition, at variance with pollen allergy, in HDM allergy asthma
is more prevalent. However, several AIT products have been approved for HDM
induced allergic rhinitis, according to their ascertained clinical efficacy,
tolerability and safety profile, particularly in the sublingual form (SLIT).
OBJECTIVE: We reviewed herein the available data on AIT in patients with HDM
induced allergic diseases, with a particular attention to the new product MK-8237
HDM-SLIT tablets, concerning its efficacy and safety profile. METHOD: In the
recent years, several randomized placebo-controlled clinical trials have been
performed in Europe, North America and Japan to evaluate the efficacy of HDM
sublingual tablets in patients with HDM-induced allergic asthma and allergic
rhinitis, mainly assessing the reduction of symptoms, exacerbations and
corticosteroid intake. RESULTS: The results of the published clinical trials were
encouraging and led to the approval and commercialization of MK-8237 HDM-SLIT
tablet. CONCLUSION: The favorable efficacy and safety profile of MK-8237 HDM-SLIT
tablets provided a consolidated therapeutic option for patients with HDM-induced
allergic rhinitis and asthma.
PMID- 28413976
TI - Laboratory Monitoring or Measurement of Direct Oral Anticoagulants (DOACs):
Advantages, Limitations and Future Challenges.
AB - BACKGROUND: The Direct Oral Anticoagulants (DOACs) represent a new generation of
antithrombotic agents, providing direct inhibition of either thrombin (factor
IIa; FIIa) or activated factor X (FXa). Around the globe, their use is
progressively rising, as these new agents replace the historical anticoagulants
(heparin and vitamin K antagonists including warfarin) for various clinical
conditions in medical practice. Other acronyms used to designate DOACs include
TSOAC (target specific oral anticoagulants) and NOAC (novel; or non-vitamin K
antagonist oral anticoagulants). Currently available DOACS include dabigatran
(FIIa inhibitor), along with rivaroxaban, apixaban, edoxaban and betrixaban (FXa
inhibitors). OBJECTIVE: This narrative review aims to briefly summarise the
evidence concerning utility of different laboratory assays for qualitative or
quantitative assessment of DOACs, emphasizing the difference between 'drug
monitoring' and 'drug measurement' and ultimately discussing advantages and
limitations of these processes. RESULTS AND CONCLUSION: Recently, the dogma that
these innovative anticoagulant agents will not necessitate laboratory testing has
been challenged with the recognition that assessment of drug concentration or
activity may be required in some circumstances, although this does not
immediately translate to the concept of 'drug monitoring'.
PMID- 28413978
TI - Advances and Challenges in Drug Design of PPARdelta Ligands.
AB - BACKGROUND: Peroxisome proliferator-activated receptors (PPAR) are nuclear
receptors activated by endogenous fatty acids and prostaglandins that are
classified into three types: alpha, gamma and delta, which have different
functions and tissue distribution. PPAR modulators have been exploited to the
treatment of important metabolic diseases, such as type 2 diabetes mellitus and
metabolic syndrome, which are considered relevant epidemic diseases currently.
Along the last decades, several studies have reported structural differences
between the three PPAR subtypes associated with the discovery of selective
ligands, dual and pan-agonists. Nowadays, there are several approved drugs that
activate PPARalpha (fibrates) and PPARgamma (glitazones), but up to now there is
none clinically used drug targeting PPARdelta. Additionally, several side-effects
associated with the use of PPARalpha and gamma agonists are reported by
regulatory agencies, which do not indicate anymore their use as first-line drugs.
OBJECTIVE: A significant new market has grown in the last years, focusing on the
development of new PPARdelta agonists as drug candidates to treat metabolic
diseases and, in this sense, this study proposes to review the structural
requirements to achieve selective PPARdelta activation, as well to discuss the
most relevant agonists in clinical trials, providing information on the current
phase in the drug discovery and design targeting PPARdelta. CONCLUSION: Several
PPARdelta ligands with high potency were reported in the literature and were
designed or discovered by a combination of experimental and computational
approaches. Furthermore, the reported importance of pockets and individual
residues at PPARdelta binding site as well as the importance of substituent and
some physicochemical properties that could help to design of new classes of
agonists.
PMID- 28413979
TI - Drug Resistance of Enzalutamide in CRPC.
AB - : Understanding and targeting the mechanisms of resistance to enzalutamide in
castration resistant prostate cancer. BACKGROUND: Enzalutamide (MDV3100, XTANDI)
is a second generation androgen receptor inhibitor that is designed for the
treatment of castration-resistant prostate cancer (CRPC) and has prolonged
survival time. The mechanisms of mdv3100 resistance have not yet been clearly
clarified and the majority of treated patients, innate or acquiring resistance
invariably arises. OBJECTIVE: The purpose of this review is to summarize the main
data available on the mechanisms of resistance to mdv3100. Understanding how the
resistance aroused may have clinical implications in underlying the usefulness of
prognostic and predictive biomarkers in daily practice and improving the
strategies. RESULTS: Resistance to MDV3100 could be basically divided into two
distinct pathways, either dependent or independent of the androgen receptor
activity. Androgen receptor (AR) axis is sitll the most important pathway for
prostate cancer cells and it is still currently regarded as a critical resistant
mechanism. CONCLUSION: Targeting these newly identified signals, especially AR
axis, could be potentially overcome through novel therapeutic agents,
synergically improve the ADT in CRPC.
PMID- 28413980
TI - Therapeutic Applications of Liposomal Based Drug Delivery and Drug Targeting for
Immune Linked Inflammatory Maladies: A Contemporary View Point.
AB - Immune-based inflammatory diseases involve immune related dysregulation in
different sites of body, which includes rheumatoid arthritis, multiple sclerosis,
inflammatory bowel disease, atherosclerosis, etc. Advancements in molecular
research have facilitated investigation of their pathogenesis that is involved in
inflammatory cytokines cells and several genes. The available drug therapy
provides suboptimal therapeutic effects and higher adverse effects. Emergence of
liposomal systems of the drugs meant for the above mentioned disease has gained
broader importance due to their high treatment efficacy by means of optimal
therapeutic drug delivery. Beyond the conventional liposomal formulations,
evolution of second generation liposomes including stealth liposomes, cationic
liposomes, immuno-liposomes, etc. has gained tremendous attention owing to their
drug target potential, diagnostic importance and imaging in treatment of above
mentioned immune mediated inflammatory disorders.
PMID- 28413981
TI - Default Mode Network Connectivity and Related White Matter Disruption in Type 2
Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment.
AB - BACKGROUND: As a risk factor for Alzheimer's disease (AD), type 2 diabetes
mellitus (T2DM) itself causes cognitive impairment and has higher prevalence of
mild cognitive impairment (MCI). OBJECTIVE: The aim of this study was to explore
the cognition especially the episodic memory difference, the DMN functional
connectivity and DMN-related white matter integrity in patients with both T2DM
and amnestic MCI (T2DM-MCI) as compared to patients with T2DM only. METHODS:
Focusing especially on T2DM population, we investigated the default mode network
(DMN) through resting-state functional magnetic resonance imaging among 22
elderly T2DM-MCI patients and 24 elderly T2DM patients. Including primarily the
bilateral cingulum, hippocampus and uncinate fasciculus, these DMN white matter
fibers were also closely associated with episodic memory and the integrity of
them was also investigated using diffusion tensor imaging in 19 elderly T2DM-MCI
patients and 23 elderly T2DM patients. RESULTS: Compared with the patients with
T2DM, the T2DM-MCI patients performed worse in several areas of cognition besides
episodic memory, and showed stronger DMN functional connectivity in the left
precuneus and weaker functional connectivity in the left calcarine, as well as
decreased integrity of the left cingulate bundle and bilateral uncinate
fasciculus. Furthermore, a correlation analysis indicated that higher left
calcarine connectivity was associated with better episodic memory performance
among the overall group. CONCLUSION: Our results demonstrated that T2DM patients
with comorbid amnestic MCI had abnormal functional connectivity patterns and
decreased white matter integrity, which could potentially serve as AD or AD risk
biomarkers for early detection of those elderly individuals with T2DM.
PMID- 28413982
TI - Optimizing ADAS-Cog Worksheets: A Survey of Clinical Trial Rater s' Perceptions.
AB - BACKGROUND: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADASCog)
remains the most widely used test of longitudinal cognitive functioning in
Alzheimer's disease (AD) clinical trials. Unlike most neuropsychological tests,
the ADAS-Cog source documentation worksheets are not uniform across clinical
trials, and vary by document layout, inclusion of administration and/or scoring
instructions, and documentation of subtest scoring (e.g., recording correct
versus incorrect scores), among other differences. Many ADAS-Cog test
administrators (raters) participate in multiple AD trials and switching between
different ADAS-Cog worksheets may increase the likelihood of administration
and/or scoring mistakes that lessen the reliability of the instrument. An
anonymous online survey sought raters' experiences with ADAS-Cog worksheets and
their opinions on the design and content of the worksheets. RESULTS: Results of
the survey indicated preference for structure and standardization of the ADASCog
worksheets, which has been considered in the development of a standard ADAS-Cog
source document by the Alzheimer's Disease Cooperative Study (ADCS) Working
Group.
PMID- 28413983
TI - Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients Control CCL4
and CXCL10 Levels in a Human Blood Brain Barrier Model.
AB - BACKGROUND: Alzheimer's disease (AD) is accompanied by a neuroinflammation
triggering chemoattractant signals towards peripheral blood mononuclear cells
(PBMCs), which in turn could reduce amyloid plaques after transmigration through
the blood brain barrier (BBB). But the chemotactic environment remains unclear.
OBJECTIVE: To analyze five chemokines known to be involved in AD in three
different cellular models to better understand the cellular and molecular
interactions in the BBB. METHOD: Chemokines (CCL-2, 4 and 5, CXCL10 and CX3CL1)
were measured in isolated cells, a BBB model without PBMCs (H4 and hCMEC/D3
cells, a neuroglioma and human endothelial cells, respectively) and in a complete
BBB model with PBMCs from AD patients at a moderate stage. In one set of
experiments, H4 cells were treated with Abeta42. RESULTS: CCL2 and CCL5
significantly increased in hCMEC/D3 and H4 cells in the complete BBB model. In
turn, the rate of CCL2 increased in PBMCs whereas for CCL5, it decreased. CXCL10
increased in all cellular actors in the complete BBB model, compared to isolated
cells. For CCL4, PBMCs induced a robust increase in H4 and hCMEC/D3. In turn, the
level of CCL4 decreased in PBMCs. Furthermore, PBMCs triggered a significant
increase in CX3CL1 in hCMEC/D3. Surprisingly, no effect of Abeta42 was observed
in the complete BBB model. CONCLUSION: These findings highlight the interest of a
BBB model in order to explore chemokine production. For the first time, results
showed that PBMCs from patients with AD can control the production of CCL4 and
CXCL10 in a human BBB model.
PMID- 28413984
TI - Prevalence of Frailty in Mild to Moderate Alzheimer's Disease: A Systematic
Review and Meta-analysis.
AB - BACKGROUND: Frailty is a state of increased vulnerability to poor resolution of
homeostasis as a consequence of age-related decreased physiological reserves.
Although physical frailty and cognitive impairment have been shown to be
associated, evidence on the prevalence of frailty in Alzheimer's disease is
scarce. OBJECTIVE: To conduct a systematic review on the prevalence of frailty
and to combine the data to synthesize the pooled prevalence of physical frailty
among patients with Alzheimer's disease. METHOD: Five electronic databases
(Embase, MEDLINE, CINAHL Plus, PsycINFO, and the Cochrane Library) were searched
for studies providing cross-sectional data on physical frailty among patients
with Alzheimer's disease published from 2000 to January 2016. RESULTS: Of 2,564
studies identified through the systematic review, five studies incorporating 534
patients with Alzheimer's disease were included for the meta-analysis. The
prevalence of frailty varied with a wide range from 11.1% to 50.0% and the pooled
prevalence was 31.9% (five studies, 95% confidence interval (CI)=15.7%-48.5%).
The high degree of heterogeneity was observed in all analyses. A borderline
publication bias was detected. CONCLUSION: The current study showed that frailty
is highly prevalent in older patients with Alzheimer's disease in the community
with the pooled prevalence of 31.9%. The true prevalence may be much higher given
that end-stage patients may not be included. This information is important for
clinicians and researchers.
PMID- 28413985
TI - Decrease in the Generation of Amyloid-beta Due to Salvianolic Acid B by
Modulating BACE1 Activity.
AB - OBJECTIVE: Generation and accumulation of the amyloid-beta (Abeta) peptide after
proteolytic processing of the full length amyloid precursor protein (FL-APP) by
beta-secretase (beta-site APP cleaving enzyme or BACE1) and gamma-secretase are
the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a
rate-limiting enzyme in the production of Abeta, is an attractive therapeutic
approach for the treatment of AD. Recent studies suggest that salvianolic acid B
(Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal
medicine commonly used for the treatment of cardiovascular, cerebrovascular and
liver diseases in China. METHOD: In this study, we discovered that Sal B acted as
a BACE1 modulator and reduced the level of secreted Abeta in two different
Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human
neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B
significantly and dose-dependently decreased the generation of extracellular
Abeta, soluble APPbeta (by-product of APP cleaved by BACE1), and intracellular C
terminal fragment beta from APP without influencing alpha-secretase and gamma
secretase activity and the levels of FL-APP. In addition, using protein-docking,
we determined the potential conformation of Sal B on BACE1 docking and revealed
the interactions of Sal B with the BACE1 catalytic center. RESULTS: The docking
provides a feasible explanation for the experimental results, especially in terms
of the molecular basis of Sal B's action. Our results indicate that Sal B is a
BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD.
PMID- 28413986
TI - Tau in Alzheimer's Disease: Mechanisms and Therapeutic Strategies.
AB - OBJECTIVE: Alzheimer's disease (AD), the most important progressive
neurodegenerative disorder, is characterized by cognitive and behavioral
disabilities. Nowadays, tau, as a microtubuleassociated protein and a principle
neuropathological hallmark of AD, provides us a neoteric perspective to explore
further aetiopathogenesis and therapeutic strategy. The hyperphosphorylation and
abnormal aggregation of tau, combined with its decreased clearance, form
neurofibrillary tangles (NFTs) and exert neurotoxicity in AD. METHODS: Recent
investigations aim to prevent the deposition of NFT and accelerate the clearance
of NFT. Intriguingly, immunization strategies targeting tau effectively
ameliorates the tau-associated pathology in AD. In addition, modified therapies
targeting tau should be regarded as a potential way to treat AD. These progresses
open new avenues for AD. CONCLUSION: Here, we review the recent literature of
potential mechanisms of the tau in AD and discuss the modified therapeutic
strategies for AD.
PMID- 28413987
TI - Alzheimer's Disease-like Early-phase Brain Pathogenesis: Self-curing Amelioration
of Neurodegeneration from Pro-inflammatory 'Wounding' to Anti-inflammatory
'Healing'.
AB - OBJECTIVE: The etiological initiators of neuroinflammation remain inconclusive,
and effective interventions to block neurodegeneration are unavailable.
Surprisingly, we found collagen II-combined complete Freund's adjuvant (CC) that
usually induces rheumatoid arthritis (RA) also drives Alzheimer's disease (AD)
like neurodegeneration in mice. CC not only upregulates the cerebral pro
inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha) and
interleukin 8 (IL-8), but also downregulates the cerebral interleukin 10 (IL-10),
an anti-inflammatory cytokine, and tyrosine hydroxylase (TH), a ratelimiting
enzyme for biosynthesis of the anti-inflammatory neurotransmitter dopamine. In
contrast, electroacupuncture (EA) elevates TNF-alpha/IL-8 and declines IL-10/TH
at first, but declines TNF-alpha/IL-8 and elevates IL-10/TH later. Upon impact on
mitochondrial biogenesis, ubiquitination, and autophagy, EA firstly potentates
but secondly attenuates CC-triggered signaling cascades leading to oxidation,
nitrosylation, hypoxia, and angiogenesis. Eventually, EA compromises
neurodegeneration by decreasing amyloid- beta peptide (Abeta) and phosphorylated
tau protein (p-tau), and also rectifies neuronal dysfunctions by increasing the
cholinergic neurotransmitter acetylcholine (Ach) and its rate-limiting
biosynthetic enzyme choline acetyltransferase (ChAT). RESULTS: Conclusively, EA
initially aggravates and subsequently ameliorates CC-evoked AD-like earlyphase
brain pathogenesis via conversion from pro-inflammatory microglia to anti
inflammatory microglia.
PMID- 28413988
TI - Cognitive Mechanisms in Decision-Making in Patients With Mild Alzheimer Disease.
AB - BACKGROUND: Alzheimer's dementia is characterized by significant cortical and
subcortical atrophy, causing diverse neuropsychological deficits. According to
the somatic marker hypothesis, the areas responsible for generating the somatic
markers that anticipate the consequences of a decision and thereby optimize the
process would be affected in these patients. OBJECTIVE: The aim of this
experiment is to study the decision-making processes in Alzheimer type dementia
patients to determine potential deficits in these processes as a result of the
disease, aside from the cognitive impairment that is typical of aging. In
addition, we wish to determine the defining characteristics of decision-making in
these patients, on the basis of the prospect valence-learning parameters. METHOD:
We evaluated 30 patients with Alzheimer's disease and a control group of 30
healthy subjects. A short version of the Iowa Gambling Task was used. RESULTS:
The results showed that patients made less advantageous choices than did
controls. Group differences were quantitative and qualitative, as significant
differences in cognitive mechanisms identified in the prospect valence-learning
decisions were observed. These results are consistent with evidence from
neuroimaging studies as well as with work carried out with amnesic patients.
CONCLUSION: That problems in our patients' decision-making could be due to the
characteristic memory deficits of this disease, which prevents them from
establishing new stimulus-reward relationships and eliminating previously learned
responses as a result of the parietal and temporal atrophy they present.
PMID- 28413989
TI - Anatomical Wrist Patterns on Plain Radiographs.
AB - BACKGROUND: Interpreting the structure in the wrist is complicated by the
existence of multiple joints as well as variability in bone shapes and anatomical
patterns. Previous studies have evaluated lunate and capitate shape in an attempt
to understand functional anatomical patterns. OBJECTIVE: The purpose of this
study was to describe anatomical shapes and wrist patterns in normal wrist
radiographs. We hypothesized that there is a significant relationship in the
midcarpal joint with at least one consistent pattern of wrist anatomy. METHOD:
Seventy plain posteroanterior (PA) and lateral wrist radiographs were evaluated.
These radiographs were part of a previously established normal database, had all
been read by a radiologist as normal, and had undergone further examination by 2
hand surgeons for quality. Evaluation included: lunate and capitate shape (type 1
and 2 lunate shape according to the classification system by Viegas et al.),
ulnar variance, radial inclination and height, and volar tilt. RESULTS: A
significant association was found between lunate and capitate shape using a
dichotomal classification system for both lunate and capitate shapes (p=0.003).
Type 1 wrists were defined as lunate type1and a spherical distal capitate. Type 2
wrists had a lunate type 2 and a flat distal capitate. No statistically
significant associations were detected between these wrist types and measurements
of the radiocarpal joint. CONCLUSION: There was a significant relationship
between the bone shapes within the midcarpal joint. These were not related to
radiocarpal anatomical shape. Further study is necessary to better describe the
two types of wrist patterns that were defined and to understand their influence
on wrist biomechanics and pathology.
PMID- 28413990
TI - Effect of Glucagon-like Peptide-1 Receptor Agonists on All-cause Mortality and
Cardiovascular Outcomes: A Meta-analysis.
AB - BACKGROUND: Cardiovascular disease is the leading cause of death in patients with
type 2 diabetes. OBJECTIVE: To assess the impact of glucagon-like peptide-1
receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant
outcomes including all-cause mortality, cardiovascular mortality, nonfatal
myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart
failure, in patients with type 2 diabetes. METHODS: EMBASE, MEDLINE, and CENTRAL
were searched (inception to September 2016) for randomized, double-blind, placebo
controlled trials of at least one year in duration that compared any GLP1RA to
placebo in patients with type 2 diabetes. Both authors independently completed
the literature search, data extraction, and risk of bias assessment. For each
outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using
a Mantel-Haenszel random effects model. RESULTS: Eight trials (three albiglutide,
two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients
were included. Most patients had, or were at high risk for, cardiovascular
disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of
data were deemed to have a low risk of bias. The risk of all-cause mortality was
lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There
was no statistically significant difference between groups with respect to
cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart
failure. CONCLUSION: GLP1RA therapy when compared to placebo reduced all-cause
mortality in high cardiovascular risk patients with type 2 diabetes. They did not
impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure
hospitalizations.
PMID- 28413991
TI - Potential Role of Endothelin in Early Vascular Aging.
AB - Early vascular aging is a process associated with gradual alterations in the
vessels, regarding their structure and function, taking a more rapid course than
normal biological aging in the arteries. In the presence of cardiovascular
disease, these age-associated alterations are accelerated, contributing in the
appearance or the progression of cardiovascular disease, such as high blood
pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most
abundant and important endothelin produced by vascular cells. ET-1 exerts its
biological actions through the activation of two receptors: ETA and ETB. Many
important functions are mediated by the activation of these receptors, such as
cardiovascular remodeling, vasoconstriction, cell proliferation and
differentiation, production of extracellular matrix, and water and sodium
secretion control. ETA receptor seems to participate in the pathogenesis and
development of diseases, such as diabetes, atherosclerosis, systemic and
pulmonary hypertension, and cardiac remodeling after myocardial ischemia, whereas
ETB receptor seems to prevent the overstimulation of ETA receptor, acting as a
clearance receptor. Increased ET-1 system activity may contribute to vascular
dysfunction in aging via multiple pathways, such as direct hemodynamic effects,
vascular oxidative stress, inflammatory activity, mitogenic stimulation of the
vascular smooth muscle cells and fibrotic processes. Endothelin receptor
antagonists were considered to be used for the treatment of some diseases like
hypertension, diabetes and chronic kidney disease. However, besides pulmonary
hypertension, this class is not in clinical use because of the side effects and
the availability of safer drugs for the treatment of these diseases.
PMID- 28413992
TI - Screening and Elucidation of Selected Natural Compounds for Anti- Alzheimer's
Potential Targeting BACE-1 Enzyme: A Case Computational Study.
AB - BACKGROUND: The present study clarifies the molecular interactions of human BACE1
with novel natural ligands and also with the well-known ligand 2, 2, 4
trihydroxychalcone and Galangin for comparison. OBJECTIVE: The study of enzyme-
ligands interaction is interesting, thus description of ligands binding to the
active site of target molecule could be beneficial for better understanding the
mechanism of the ligand on the target molecule. METHODS: Lipinski rule of five
and docking study were performed between ligands and enzyme using 'Autodock4.2'.
RESULTS: It was found that hydrogen bond interactions play a significant role in
the accurate positioning of ligands within the 'active site' of BACE1 to permit
docking. Such information may aid to propose the BACE1 -inhibitors and is
estimated to aid in the safe medical use of ligands. Selected ligands of BACE1
also inhibit the aggregated amyloid beta peptide. The aggregation of amyloid
peptides Abeta1-42 may be responsible for AD. CONCLUSION: Scope lies in the
determination of the 3-dimensional structure of BACE1 and ligands complex by X
ray crystallography to certify the explained data. To validate the enzyme
ligands results, we considered 2, 2, 4-trihydroxychalconeas and Galangin as a
positive control. Moreover, the current study verifies that ligands are more
capable inhibitors of human BACE1 compared to positive control with reference to
DeltaG values.
PMID- 28413993
TI - Efficacy of Sofosbuvir Plus Ribavirin with or Without Peginterferon- Alfa in
Treatment of a Cohort of Egyptian Patients with Hepatitis C Virus Infection.
AB - : Background & Aims: Sofosbuvir is a powerful drug for the treatment of hepatitis
C virus (HCV) infection. In comparison to preceding remedies, sofosbuvirbased
regimens provide a higher cure rate, fewer side effects, and much lower duration
of treatment. The aim of the work was to assess the efficacy and safety of
sofosbuvir plus ribavirin with or without peginterferon-alfa in the treatment of
a cohort of Egyptian patients with hepatitis C virus infection. METHODS: Two
hundred treatment naive patients who were HCV-antibody positive and HCV RNA by
PCR positive aged more than 18 years were enrolled in the study and patients were
classified into two groups: Group I which included 100 patients who received dual
therapy with sofosbuvir plus oral weight based ribavirin for 24 weeks and Group
II which included 100 patients on triple therapy with sofosbuvir plus oral weight
based ribavirin (as with the dual therapy) and a 180 mcg Peg-INF alpha 2a
subcutaneous injection weekly for 12 weeks. The primary end point was a sustained
virological response at 12 weeks after end of the treatment determined by
quantitative PCR for HCV. RESULTS: Both patients groups had high sustained
virological response that was higher in patients receiving triple than dual
therapy (94% vs 83%). The adverse events that occurred in the two groups of
patients were more evident in a group of patients receiving triple therapy. The
side effects were mainly flu like symptoms. CONCLUSIONS: The triple regimen of
Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the
treatment of Egyptian patients with hepatitis C virus as well as sofosbuvir and
ribavirin alone wit.
PMID- 28413994
TI - Biotic Strategies for Toxic Heavy Metal Decontamination.
AB - BACKGROUND: In the modern age of globalization and fast industrialization, the
environmental matters are fetching more and more annoyance for human being.
Patents reveal that heavy metals occur in immobilized form in sediments and as
aggregates in nature. However due to the different human activities like ore
mining and industrial processes, the natural biogeochemical cycles are disordered
instigating amplified deposition of heavy metals in aquatic environments. The
most common pollution causing heavy metals are considered to be the mercury,
arsenic, lead, copper, silver, cadmium. OBJECTIVE: The goal of this work is to
identify the biological action of heavy metal-contaminated water and sediments
which can be categorized into bioaccumulation, biosorption, oxidation/ reduction,
leaching, degradation, and phytoremediation. DISCUSSION: Among the various
biological methods for decontamination of heavy metals from water, biosorption is
known to be the most affordable, economical and efficient option for the
management of capacious water bodies encompassing low concentrations of heavy
metals. However, the physicochemical properties of the aquatic bodies that would
extremely affect the performances of biosorbents should be prudently measured.
The precipitation is efficient in decontamination/removal of relatively high
concentrations of metals in water. The bioleaching of searched sediments in
regulated systems is a speedy process as compared with phytoremediation.
CONCLUSION: In order to decontaminate the heavy metals from water, biological
methods are very proficient and useful. These methods can be very efficient in
cleaning up environment.
PMID- 28413995
TI - The burden of seasonal respiratory infections on a national telehealth service in
England.
AB - Seasonal respiratory illnesses present a major burden on primary care services.
We assessed the burden of respiratory illness on a national telehealth system in
England and investigated the potential for providing early warning of respiratory
infection. We compared weekly laboratory reports for respiratory pathogens with
telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple
linear regression was used to identify which pathogens had a significant
association with respiratory calls. Children aged <5 and 5-14 years, and adults
over 65 years were modelled separately as were time lags of up to 4 weeks between
calls and laboratory specimen dates. Associations with respiratory pathogens
explained over 83% of the variation in cold/flu, cough and difficulty breathing
calls. Based on the first two seasons available, the greatest burden was
associated with respiratory syncytial virus (RSV) and influenza, with
associations found in all age bands. The most sensitive signal for influenza was
calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting
models showed calls increasing a week before laboratory specimen dates. Daily
surveillance of these calls can provide early warning of seasonal rises in
influenza and RSV, contributing to the national respiratory surveillance
programme.
PMID- 28413996
TI - From VAP to VAE: Implications of the New CDC Definitions on a Burn Intensive Care
Unit Population.
AB - Ventilator-associated pneumonia (VAP) is a frequent complication of severe burn
injury. Comparing the current ventilator-associated event-possible VAP definition
to the pre-2013 VAP definition, we identified considerably fewer VAP cases in our
burn ICU. The new definition does not capture many VAP cases that would have been
reported using the pre-2013 definition. Infect Control Hosp Epidemiol 2017;38:867
869.
PMID- 28413998
TI - Optimising treatment strategies for ADHD in adolescence to minimise 'lost in
transition' to adulthood.
AB - The persistence of attention-deficit hyperactivity disorder (ADHD) from
adolescence to adulthood is not matched by continuity of care in this transition
period. Many adolescents with ADHD have poor medication adherence or even stop
medication treatment, and use of behavioural interventions is also suboptimal.
The present commentary focuses on treatment strategies that might improve effects
of ADHD medication treatment by improving adherence in adolescents with ADHD
and/or optimise behavioural interventions for ADHD in adolescence. Most treatment
strategies in adolescents with ADHD are merely copied from treatments offered to
children. Instead however treatment should be focused on what makes adolescents
special and vulnerable, such as poor insight into own functioning and poor
decision making. Techniques that offer promise for adolescents are motivational
interviewing, use of ecological momentary assessments and interventions,
mindfulness-based training and serious games. Systematic studies into the effects
of these techniques alone and in combination with medication are lacking.
PMID- 28413997
TI - Differences in meal patterns and timing with regard to central obesity in the
ANIBES ('Anthropometric data, macronutrients and micronutrients intake, practice
of physical activity, socioeconomic data and lifestyles in Spain') Study.
AB - OBJECTIVE: To study the association of meal patterns and timing with central
obesity to identify the best dietary strategies to deal with the increasing
obesity prevalence. DESIGN: A cross-sectional study performed on data from a
representative sample of the Spanish population. Height and waist circumference
were measured using standardized procedures and waist-to-height ratio (WHtR) was
calculated. The sample was divided into those without central obesity (WHtR<0.5)
and those with central obesity (WHtR>=0.5). SETTING: ANIBES ('Anthropometric
data, macronutrients and micronutrients intake, practice of physical activity,
socioeconomic data and lifestyles in Spain') Study. SUBJECTS: Adults aged 18-64
years (n 1655; 798 men and 857 women). RESULTS: A higher percentage of people ate
more than four meals daily in the group without central obesity and those with
central obesity more frequently skipped the mid-afternoon snack than those
without. Breakfasts containing >25 % of total energy intake and lunches
containing >35 % of total energy intake were associated with increased likelihood
of central obesity (OR=1.874, 95 % CI 1.019, 3.448; P15 % of total energy were
associated with decreased likelihood of central obesity (OR=0.477, 95 % CI 0.313,
0.727; P<0.001 and OR=0.650, 95 % CI 0.453, 0.932; P<0.05, respectively). The
variety of cereals, wholegrain cereals and dairy was higher in the population
without central obesity. CONCLUSIONS: Our results suggest that 'what and when we
eat' should be considered dietary strategies to reduce central obesity.
PMID- 28413999
TI - Improving Sensitivity to Detect Mild Cognitive Impairment: Cognitive Load Dual
Task Gait Speed Assessment.
AB - OBJECTIVES: Longitudinal research indicates that cognitive load dual-task gait
assessment is predictive of cognitive decline and thus might provide a sensitive
measure to screen for mild cognitive impairment (MCI). However, research among
older adults being clinically evaluated for cognitive concerns, a defining
feature of MCI, is lacking. The present study investigated the effect of
performing a cognitive task on normal walking speed in patients presenting to a
memory clinic with cognitive complaints. METHODS: Sixty-one patients with a mean
age of 68 years underwent comprehensive neuropsychological testing, clinical
interview, and gait speed (simple- and dual-task conditions) assessments. Thirty
four of the 61 patients met criteria for MCI. RESULTS: Repeated measure analyses
of covariance revealed that greater age and MCI both significantly associated
with slower gait speed, ps<.05. Follow-up analysis indicated that the MCI group
had significantly slower dual-task gait speed but did not differ in simple-gait
speed. Multivariate linear regression across groups found that executive
attention performance accounted for 27.4% of the variance in dual-task gait speed
beyond relevant demographic and health risk factors. CONCLUSIONS: The present
study increases the external validity of dual-task gait assessment of MCI.
Differences in dual-task gait speed appears to be largely attributable to
executive attention processes. These findings have clinical implications as they
demonstrate expected patterns of gait-brain behavior relationships in response to
a cognitive dual task within a clinically representative population. Cognitive
load dual-task gait assessment may provide a cost efficient and sensitive measure
to detect older adults at high risk of a dementia disorder. (JINS, 2017, 23, 493
501).
PMID- 28414000
TI - Maternal mind-mindedness and toddler behavior problems: The moderating role of
maternal trauma and posttraumatic stress.
AB - Maternal mind-mindedness (MM) reflects a caregiver's tendency to view a child as
an individual with an independent mind. Research has linked higher MM with more
favorable parenting and child adaptation. The aim of this study was to examine
whether MM was associated with toddlers' behavior problems and competence, and
the moderating role of trauma and posttraumatic stress disorder (PTSD) in a
sample (N = 212) of adolescent mothers and their toddlers. MM was coded from
maternal utterances during free play; mothers completed the University of
California at Los Angeles Trauma and Posttraumatic Stress Disorder Reaction Index
and reported on children's behavior problems and competence using the Brief
Infant-Toddler Social and Emotional Assessment. The majority of mothers (84%)
experienced trauma; 45% of these mothers met criteria for partial or full PTSD.
Trauma was related to greater behavior problems, and PTSD moderated MM-child
functioning relations. When mothers experienced full PTSD, there was no relation
between MM and behavior problems. With child competence, when compared to
children of mothers with no trauma exposure, children of mothers experiencing
partial PTSD symptoms were more likely to have delays in competence when mothers
made more MM comments. Results are discussed in light of how MM, in the context
of trauma and PTSD, may affect parenting.
PMID- 28414001
TI - Transcatheter closure of a residual aorto-left ventricular tunnel: report of a
case with a 6-year follow-up.
AB - Aorto-left ventricular tunnel is an exceedingly rare congenital cardiac defect.
Early surgical closure is the treatment of choice. Residual or recurrent tunnel
and aortic valve insufficiency are well-recognised complications after surgical
repair. In this article, we report on successful transcatheter closure of a
residual aorto-left ventricular tunnel using an Amplatzer duct occluder in a 7
year-old boy. The outcome after 6 years of follow-up is encouraging.
PMID- 28414003
TI - Regulatory theory: commercially sustainable markets rely upon satisfying the
public interest in obtaining credible goods.
AB - Regulatory theory is premised on the failure of markets, prompting a focus on
regulators and industry from economic perspectives. This article argues that
overlooking the public interest in the sustainability of commercial markets risks
markets failing completely. This point is exemplified through health care markets
- meeting an essential need - and focuses upon innovative medicines as the most
desired products in that market. If this seemingly invulnerable market risks
failure, there is a pressing need to consider the public interest in sustainable
markets within regulatory literature and practice. Innovative medicines are
credence goods, meaning that the sustainability of the market fundamentally
relies upon the public trusting regulators to vouch for product quality. Yet,
quality is being eroded by patent bodies focused on economic benefits from market
growth, rather than ensuring innovatory value. Remunerative bodies are not
funding medicines relative to market value, and market authorisation bodies are
not vouching for robust safety standards or confining market entry to products
for 'unmet medical need'. Arguably, this failure to assure quality heightens the
risk of the market failing where it cannot be substituted by the reputation or
credibility of providers of goods and/or information such as health care
professionals/institutions, patient groups or industry.
PMID- 28414002
TI - Global importation and population risk factors for measles in New Zealand: a case
study for highly immunized populations.
AB - As endemic measles is eliminated through immunization, countries must determine
the risk factors for the importation of measles into highly immunized populations
to target control measures. Despite eliminating endemic measles, New Zealand
suffers from outbreaks after introductions from abroad, enabling us to use it as
a model for measles introduction risk. We used a generalized linear model to
analyze risk factors for 1137 measles cases from 2007 to June 2014, provide
estimates of national immunity levels, and model measles importation risk. People
of European ethnicity made up the majority of measles cases. Age is a positive
risk factor, particularly 0-2-year-olds and 5-17-year-old Europeans, along with
increased wealth. Pacific islanders were also at greater risk, but due to 0-2
year-old cases. Despite recent high measles, mumps, and rubella vaccine
immunization coverage, overall population immunity against measles remains ~90%
and is lower in people born between 1982 and 2005. Greatest measles importation
risk is during December, and countries predicted to be sources have historical
connections and highest travel rates (Australia and UK), followed by Asian
countries with high travel rates and higher measles incidences. Our results
suggest measles importation due to travel is seeding measles outbreaks, and
immunization levels are insufficient to continue to prevent outbreaks because of
heterogeneous immunity in the population, leaving particular age groups at risk.
PMID- 28414004
TI - Clinical, virological and epidemiological characterization of dengue outbreak in
Myanmar, 2015.
AB - Hospital-based surveillance was conducted at two widely separated regions in
Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected
from 332 clinically diagnosed dengue patients during the peak season of dengue
cases. Viremia levels were measured by quantitative real-time PCR and plaque
assays using FcgammaRIIA-expressing and non-FcgammaRIIA-expressing BHK cells to
specifically determine the infectious virus particles. By serology and molecular
techniques, 280/332 (84.3%) were confirmed as dengue patients. All four serotypes
of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients
including two cases infected with two DENV serotypes. High percentage of primary
infection was noted among the severe dengue patients. Patients with primary
infection or DENV IgM negative demonstrated significantly higher viral loads but
there was no significant difference among the severity groups. Viremia levels
among dengue patients were notably high for a long period which was assumed to
support the spread of the virus by the mosquito vector during epidemic.
Phylogenetic analyses of the envelope gene of the epidemic strains revealed close
similarity with the strains previously isolated in Myanmar and neighboring
countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3)
and genotype distributions were similar in both study sites.
PMID- 28414005
TI - Health care and health innovation in Europe: regulating for public benefit or for
commercial profit?
PMID- 28414006
TI - Unit cost of common illness management: a comparison between a primary care unit
and a community pharmacy in Thailand.
AB - : Aim This study was to perform unit cost analysis of managing common illnesses
comparing between a primary care unit (PCU) and a community pharmacy. BACKGROUND:
PCU is a key point of access for primary care in Thailand. Although a community
pharmacy is an ideal setting, it has not been successfully incorporated in
Thailand's health service. Common illnesses are encountered everyday by community
pharmacists, an appropriate compensation for this service has not been
established. METHODS: A primary care service of one educational institution was a
study site. Eight common illnesses were emphasised. Patient visits were observed,
prospectively at community pharmacy and retrospectively at PCU, during August to
October 2013. Labour and material costs related to management of common illnesses
were recorded. Total cost divided by total patient visits determined the unit
cost. For the community pharmacy, patients were followed up after 3-14 days of
visit to evaluate the effectiveness. Sensitivity analysis was performed by
varying direct medical cost at +/-10-30%. Findings At the community pharmacy,
community pharmacists performed multiple tasks including interviewing and
assessing patients, choosing an appropriate treatment and dispensing. Of 9141
visits, 775 (8.5%) with common illnesses were included. Upper respiratory
disorder was found the highest 41.9% (325/755). Unit cost of treatment ranged
from 54.16 baht (L1.18) for pain to 82.71 baht (L1.80) for skin disorder. Two
thirds of pharmacy visits (77.9%, 539/692) reported complete recovery. Managing
common illnesses at the PCU was performed by nurse assistants, nurses, doctors
and pharmacists. Of 6701 patient visits to the PCU, 1545 (23.1%) visits were at
least one of the eight illnesses. Upper respiratory disorder was the majority,
53.0% (771/1454). Unit cost of treatment ranged from 85.39 baht (L1.86) for
eye/ear to 245.93 baht (L5.36) for sexual health. Managing common illness at a
community pharmacy shows satisfactory effectiveness with lower unit cost.
PMID- 28414007
TI - Pokemon Go: digital health interventions to reduce cardiovascular risk.
AB - Physical activity is associated with a lower risk of coronary heart
disease/cardiovascular disease mortality, and current guidelines recommend
physical activity for primary prevention in healthy individuals and secondary
prevention in patients with coronary heart disease/cardiovascular disease. Over
the last decade, playing classic video games has become one of the most popular
leisure activities in the world, but is associated with a sedentary lifestyle. In
the new era of rapidly evolving augmented reality technology, Pokemon Go, a well
known augmented reality game, may promote physical activity and prevent
cardiovascular disease risks - that is, diabetes, obesity, and hypertension.
Pokemon Go makes players willing to be physically active for regular and long
periods of time. We report on an assessment of regular walking and playing
Pokemon Go by performing data mining in Twitter.
PMID- 28414008
TI - Implementation, utilization and influence of a community-based participatory
nutrition promotion programme in rural Ethiopia: programme impact pathway
analysis.
AB - OBJECTIVE: A community-based participatory nutrition promotion (CPNP) programme,
involving a 2-week group nutrition session, attempted to improve child feeding
and hygiene. The implementation, utilization and influence of the CPNP programme
were examined by programme impact pathway (PIP) analysis. DESIGN: Five CPNP
programme components were evaluated: (i) degree of implementation; (ii)
participants' perception of the nutrition sessions; (iii) participants' message
recall; (iv) utilization of feeding and hygiene practices at early programme
stage; and (v) participants' engagement in other programmes. SETTING: Habro and
Melka Bello districts, Ethiopia. SUBJECTS: Records of 372 nutrition sessions, as
part of a cluster-randomized trial, among mothers (n 876 in intervention area, n
914 in control area) from a household survey and CPNP participants (n 197) from a
recall survey. RESULTS: Overall, most activities related to nutrition sessions
were successfully operated with high fidelity (>90 %), but a few elements of the
protocol were only moderately achieved. The recall survey among participants
showed a positive perception of the sessions (~90 %) and a moderate level of
message recall (~65 %). The household survey found that the CPNP participants had
higher minimum dietary diversity at the early stage (34.0 v. 19.9 %, P=0.01) and
a higher involvement in the Essential Nutrition Action (ENA) programme over a
year of follow-up (28.2 v. 18.3 %; P<0.0001) compared with non-participants
within the intervention area. CONCLUSIONS: Our PIP analysis suggests that CPNP
was feasibly implemented, promoted a sustained utilization of proper feeding
behaviours, and enhanced participation in the existing ENA programme. These
findings provide a possible explanation to understanding CPNP's effectiveness.
PMID- 28414009
TI - Adenosine Triphosphate Quantification Correlates Poorly with Microbial
Contamination of Duodenoscopes.
AB - OBJECTIVE The aim of this study was to quantify the correlation between adenosine
triphosphate (ATP) measurements and bacterial cultures from duodenoscopes for
evaluation of contamination following high-level disinfection. DESIGN
Duodenoscopes used for any intended endoscopic retrograde
cholangiopancreatography (ERCP) procedure were included. Microbiologic and ATP
data were collected concomitantly and in the same manner from ERCP duodenoscopes.
SETTING A high-volume endoscopy unit at a tertiary referral acute-care facility.
METHODS Duodenoscopes were sampled for ATP and bacterial contamination in a
contemporaneous and highly standardized fashion using a "flush-brush-flush"
method for the working channel (WC) and a dry flocked swab for the elevator
mechanism (EM). Specimens were processed for any aerobic bacterial growth (colony
forming units, CFU). Growth of CFU>0 and ATP relative light unit (RLU)>0 was
considered a contaminated result. Frequency of discord between among WC and EM
measurements were calculated using 2*2 contingency tables. The Spearman
correlation coefficient was used to calculate the relatedness of bacterial
contamination and ATP as continuous measurements. RESULTS The Spearman
correlation coefficient did not demonstrate significant relatedness between ATP
and CFU for either a WC or EM site. Among 390 duodenoscope sampling events, ATP
and CFU assessments of contamination were discordant in 82 of 390 WC measurements
(21%) and 331 of 390 of EM measurements (84.9%). The EM was frequently and
markedly positive by ATP measurement. CONCLUSION ATP measurements correlate
poorly with a microbiologic standard assessing duodenoscope contamination,
particularly for EM sampling. ATP may reflect biological material other than
nonviable aerobic bacteria and may not serve as an adequate marker of bacterial
contamination. Infect Control Hosp Epidemiol 2017;38:678-684.
PMID- 28414010
TI - Letter to the Editor: Beyond childhood trauma - stressful events early and later
in life in relation to psychotic experiences.
PMID- 28414011
TI - Transradial approach for collateral embolisation.
AB - Significant aortopulmonary collaterals in cyanotic CHD patients require closure
immediately before definitive intracardiac repair. Traditionally, the
transfemoral access has been used for this purpose; however in a few cases,
selective and stable hooking of collaterals may be extremely difficult. We
describe a case in which we used a new approach for collateral embolisation in a
difficult situation.
PMID- 28414012
TI - Reasons for optimism in the search for new vaccines for tuberculosis.
AB - In the development of vaccines for tuberculosis (TB), the combination of the
will, funding, scientific rigor, new tools, refined animal models and improved
clinical trial designs are all converging at an opportune moment. The lack of
optimism that has surrounded the likelihood for finding novel TB vaccines has
resulted from a lack of correlates of vaccine-induced protection, a lack of tool
candidate vaccines to probe the immunologic space, which may be needed, and the
negative result of one recent trial. A vaccine for TB that can be delivered at a
reasonable cost to the marketplace will have greater impact on the incidence of
new cases of TB than any intervention in world history. Now is the time to
increase resources, both financial and human intellectual capacity, for a global
tuberculosis vaccine effort.
PMID- 28414013
TI - The efficacy of primary care chaplaincy compared with antidepressants: a
retrospective study comparing chaplaincy with antidepressants.
AB - : Aim To determine the effectiveness of primary care chaplaincy (PCC) when used
as the sole intervention, with outcomes being compared directly with those of
antidepressants. This was to be carried out in a homogenous study population
reflective of certain demographics in the United Kingdom. BACKGROUND: Increasing
numbers of patients are living with long-term conditions and 'modern maladies'
and are experiencing loss of well-being and depression. There is an increasing
move to utilise non-pharmacological interventions such as 'talking therapies'
within this context. Chaplaincy is one such 'talking therapy' but within primary
care its evidence base is sparse with only one quantitative study to date. There
is therefore a need to evaluate PCC excluding those co-prescribed
antidepressants, as this is not evidenced in the literature as yet. PCC also
needs to be directly compared with the use of antidepressants to justify its use
as a valid alternative treatment for loss of well-being and depression. METHODS:
This was a retrospective observational study based on routinely collected data.
There were 107 patients in the PCC group and 106 in the antidepressant group.
Socio-demographic data were collected. Their pre- and post-intervention (either
chaplaincy or antidepressant) well-being was assessed, by the Warwick-Edinburgh
Mental Well-being Scale (WEMWBS) which is a validated Likert scale. Findings The
majority of both groups were female with both groups showing marked ethnic
homogeneity. PCC was associated with a significant and clinically meaningful
improvement in well-being at a mean follow-up of 80 days. This treatment effect
was maintained after those co-prescribed antidepressants were removed. PCC was
associated with an improvement in well-being similar to that of antidepressants
with no significant difference between the two groups.
PMID- 28414014
TI - Do DSM-5 Section II personality disorders and Section III personality trait
domains reflect the same genetic and environmental risk factors?
AB - BACKGROUND: DSM-5 includes two conceptualizations of personality disorders (PDs).
The classification in Section II is identical to the one found in DSM-IV, and
includes 10 categorical PDs. The Alternative Model (Section III) includes
criteria for dimensional measures of maladaptive personality traits organized
into five domains. The degree to which the two conceptualizations reflect the
same etiological factors is not known. METHODS: We use data from a large
population-based sample of adult twins from the Norwegian Institute of Public
Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory
that indexes the five domains of the DSM-5 Alternative Model plus a domain
explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline,
Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the
maladaptive personality traits and 10 years previously. Schizoid, Histrionic,
Narcissistic, and Dependent PDs were only assessed at the first interview.
Biometric models were used to estimate overlap in genetic and environmental risk
factors. RESULTS: When measured concurrently, there was 100% genetic overlap
between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial,
Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared
with the domains. Genetic correlations between the individual domains and PDs
ranged from +0.21 to +0.91. CONCLUSION: The pathological personality trait
domains, which are part of the Alternative Model for classification of PDs in DSM
5 Section III, appears to tap, at an aggregate level, the same genetic risk
factors as the DSM-5 Section II classification for most of the PDs.
PMID- 28414015
TI - Effects of depression, metabolic syndrome, and cardiorespiratory fitness on
mortality: results from the Cooper Center Longitudinal Study.
AB - BACKGROUND: Depression and metabolic syndrome (MetS) are frequently comorbid
disorders that are independently associated with premature mortality. Conversely,
cardiorespiratory fitness (CRF) is associated with reduced mortality risk. These
factors may interact to impact mortality; however, their effects have not been
assessed concurrently. This analysis assessed the mortality risk of comorbid
depression/MetS and the effect of CRF on mortality in those with depression/MetS.
METHODS: Prospective study of 47 702 adults in the Cooper Center Longitudinal
Study. Mortality status was attained from the National Death Index. History of
depression was determined by patient response (yes or no) to a standardized
medical history questionnaire. MetS was categorized using the American Heart
Association/National Heart, Lung, and Blood Institute criteria. CRF was estimated
from the final speed/grade of a treadmill graded exercise test. RESULTS: 13.9%
reported a history of depression, 21.4% met criteria for MetS, and 3.0% met
criteria for both MetS and history of depression. History of depression (HR =
1.24, p = 0.003) and MetS (HR = 1.28, p < 0.001) were independently associated
with an increased mortality risk, with the greatest mortality risk among
individuals with both a history of depression and MetS (HR = 1.59, p < 0.001).
Higher CRF was associated with a significantly lower risk of mortality (p <
0.001) in all individuals, including those with MetS and/or a history of
depression. CONCLUSIONS: Those with higher levels CRF had reduced mortality risk
in the context of depression/MetS. Interventions that improve CRF could have
substantial impact on the health of persons with depression/MetS.
PMID- 28414016
TI - Accidental Occupational Exposure to Burkholderia pseudomallei in South Korea Did
Not Result in Melioidosis.
PMID- 28414017
TI - The prevalence of antenatal and postnatal co-morbid anxiety and depression: a
meta-analysis.
AB - To date, the precise prevalence of co-morbidity of anxiety and depression in the
perinatal period is not well known. We aimed to estimate the prevalence of co
morbid anxiety and depression in the antenatal and postnatal periods. Systematic
searches of multiple electronic databases were conducted for studies published
between January 1950 and January 2016. We included 66 (24 published and 42
unpublished) studies incorporating 162 120 women from 30 countries. Prevalence of
self-reported antenatal anxiety symptoms and mild to severe depressive symptoms
was 9.5% [95% confidence interval (CI) 7.8-11.2, 17 studies, n = 25 592] and of
co-morbid anxiety symptoms and moderate/severe depressive symptoms was 6.3% (95%
CI 4.8-7.7, 17 studies, n = 27 270). Prevalence of a clinical diagnosis of any
antenatal anxiety disorder and depression was 9.3% (95% CI 4.0-14.7, 10 studies,
n = 3918) and of co-morbid generalized anxiety disorder and depression was 1.7%
(95% CI 0.2-3.1, three studies, n = 3085). Postnatally between 1 and 24 weeks
postpartum, the prevalence of co-morbid anxiety symptoms and mild to severe
depressive symptoms was 8.2% (95% CI 6.5-9.9, 15 studies, n = 14 731), while co
morbid anxiety symptoms and moderate/severe depressive symptoms was 5.7% (95% CI
4.3-7.1, 13 studies, n = 20 849). The prevalence of a clinical diagnosis of co
morbid anxiety and depression was 4.2% (95% CI 1.9-6.6, eight studies, n = 3251).
Prevalence rates did not differ with regard to year of publication, country
income, selection bias and attrition bias. The results suggest that co-morbid
perinatal anxiety and depression are prevalent and warrant clinical attention
given the potential negative child developmental consequences if left untreated.
Further research is warranted to develop evidence-based interventions for
prevention, identification and treatment of this co-morbidity.
PMID- 28414018
TI - Psychological flexibility mediates change in intuitive eating regulation in
acceptance and commitment therapy interventions.
AB - OBJECTIVE: Despite the promising results related to intuitive eating, few studies
have attempted to explain the processes encouraging this adaptive eating
behaviour. The focus of the present study was on exploring mechanisms of change
in intuitive eating and weight in acceptance and commitment therapy (ACT)
interventions. Mediation provides important information regarding the treatment
processes and theoretical models related to specific treatment approaches. The
study investigates whether psychological flexibility, mindfulness skills and
sense of coherence mediated the interventions' effect on intuitive eating and
weight. DESIGN: Secondary analysis of a randomized control trial. Mediation
analysis compared two ACT interventions - face-to-face (in a group) and mobile
(individually) - with a control group using a latent difference score model.
Settings Data were collected in three Finnish towns. SUBJECTS: The participants
were overweight or obese (n 219), reporting symptoms of perceived stress.
RESULTS: The effect of the interventions on participants' (i) BMI, (ii) intuitive
eating and its subscales, (iii) eating for physical rather than emotional reasons
and (iv) reliance on internal hunger and satiety cues was mediated by changes in
weight-related psychological flexibility in both ACT groups. CONCLUSIONS: These
findings suggest that ACT interventions aiming for lifestyle changes mediate the
intervention effects through the enhanced ability to continue with valued
activities even when confronted with negative emotions and thoughts related to
weight.
PMID- 28414019
TI - Parental depressive history, parenting styles, and child psychopathology over 6
years: The contribution of each parent's depressive history to the other's
parenting styles.
AB - The link between parental depressive history and parenting styles is well
established, as is the association of parenting with child psychopathology.
However, little research has examined whether a depressive history in one parent
predicts the parenting style of the other parent. As well, relatively little
research has tested transactional models of the parenting-child psychopathology
relationship in the context of parents' depressive histories. In this study,
mothers and fathers of 392 children were assessed for a lifetime history of major
depression when their children were 3 years old. They then completed measures of
permissiveness and authoritarianism and their child's internalizing and
externalizing symptoms when children were 3, 6, and 9 years old. The results
showed that a depressive history in one parent predicted the other parent's
permissiveness. Analyses then showed that child externalizing symptoms at age 3
predicted maternal permissiveness and authoritarianism and paternal
permissiveness at age 6. Maternal permissiveness at age 6 predicted child
externalizing symptoms at age 9. No relationships in either direction were found
between parenting styles and child internalizing symptoms. The results highlight
the importance of considering both parents' depressive histories when
understanding parenting styles, and support transactional models of parenting
styles and child externalizing symptoms.
PMID- 28414020
TI - Modifying Alcohol Consumption to Reduce Obesity (MACRO): development and
feasibility trial of a complex community-based intervention for men.
AB - BACKGROUND: Obese men who consume alcohol are at a greatly increased risk of
liver disease; those who drink > 14 units of alcohol per week have a 19-fold
increased risk of dying from liver disease. OBJECTIVES: To develop an
intervention to reduce alcohol consumption in obese men and to assess the
feasibility of a randomised controlled trial (RCT) to investigate its
effectiveness. DESIGN OF THE INTERVENTION: The intervention was developed using
formative research, public involvement and behaviour change theory. It was
organised in two phases, comprising a face-to-face session with trained laypeople
(study co-ordinators) followed by a series of text messages. Participants
explored how alcohol consumption contributed to weight gain, both through direct
calorie consumption and through its effect on increasing food consumption,
particularly of high-calorie foodstuffs. Men were encouraged to set goals to
reduce their alcohol consumption and to make specific plans to do so. The
comparator group received an active control in the form of a conventional alcohol
brief intervention. Randomisation was carried out using the secure remote web
based system provided by the Tayside Clinical Trials Unit. Randomisation was
stratified by the recruitment method and restricted using block sizes of randomly
varying lengths. Members of the public were involved in the development of all
study methods. SETTING: Men were recruited from the community, from primary care
registers and by time-space sampling (TSS). The intervention was delivered in
community settings such as the participant's home, community centres and
libraries. PARTICIPANTS: Men aged 35-64 years who had a body mass index (BMI) of
> 30 kg/m2 and who drank > 21 units of alcohol per week. RESULTS: The screening
methods successfully identified participants meeting the entry criteria. Trial
recruitment was successful, with 69 men (36 from 419 approached in primary care,
and 33 from 470 approached via TSS) recruited and randomised in 3 months. Of the
69 men randomised, 35 were allocated to the intervention group and 34 to the
control group. The analysis was conducted on 31 participants from the
intervention group and 30 from the control group. The participants covered a wide
range of ages and socioeconomic statuses. The average alcohol consumption of the
men recruited was 47.2 units per week, more than twice that of the entry
criterion (> 21 units per week). Most (78%) engaged in binge drinking (> 8 units
in a session) at least weekly. Almost all (95%) exceeded the threshold for a 19
fold increase in the risk of dying from liver disease (BMI of > 30 kg/m2 and > 14
units of alcohol per week). Despite this, they believed that they were at low
risk of harm from alcohol, possibly because they seldom suffered acute harms
(e.g. hangovers) and made few visits to a general practitioner or hospital.
INTERVENTION: The intervention was delivered with high fidelity. A high follow-up
rate was achieved (98%) and the outcomes for the full RCT were measured. A
process evaluation showed that participants engaged with the main components of
the intervention. The acceptability of the study methods was high. CONCLUSIONS:
This feasibility study developed a novel intervention and evaluated all of the
stages of a RCT that would test the effectiveness of the intervention. The main
stages of a trial were completed successfully: recruitment, randomisation,
intervention delivery, follow-up and measurement of study outcomes. Most of the
men recruited drank very heavily and were also obese. This places them at a very
high risk of liver disease, making them a priority for intervention. FUTURE WORK:
A RCT to test the effectiveness and cost-effectiveness of the intervention. TRIAL
REGISTRATION: Current Controlled Trials ISRCTN55309164. FUNDING: This project was
funded by the National Institute for Health Research (NIHR) Health Technology
Assessment programme and will be published in full in Health Technology
Assessment; Vol. 21, No. 19. See the NIHR Journals Library website for further
project information.
PMID- 28414021
TI - Elliptical broken line method for calculating capillary density in nailfold
capillaroscopy: Proposal and evaluation.
AB - Nailfold capillaroscopy is a practical method for identifying and obtaining
morphological changes in capillaries which might reveal relevant information
about diseases and health. Capillaroscopy is harmless, and seems simple and
repeatable. However, there is lack of established guidelines and instructions for
acquisition as well as the interpretation of the obtained images; which might
lead to various ambiguities. In addition, assessment and interpretation of the
acquired images are very subjective. In an attempt to overcome some of these
problems, in this study a new modified technique for assessment of nailfold
capillary density is introduced. The new method is named elliptic broken line
(EBL) which is an extension of the two previously known methods by defining clear
criteria for finding the apex of capillaries in different scenarios by using a
fitted elliptic. A graphical user interface (GUI) is developed for pre
processing, manual assessment of capillary apexes and automatic correction of
selected apexes based on 90 degrees rule. Intra- and inter-observer reliability
of EBL and corrected EBL is evaluated in this study. Four independent observers
familiar with capillaroscopy performed the assessment for 200 nailfold
videocapillaroscopy images, form healthy subject and systemic lupus erythematosus
patients, in two different sessions. The results show elevation from moderate
(ICC=0.691) and good (ICC=0.753) agreements to good (ICC=0.750) and good
(ICC=0.801) for intra- and inter-observer reliability after automatic correction
of EBL. This clearly shows the potential of this method to improve the
reliability and repeatability of assessment which motivates us for further
development of automatic tool for EBL method.
PMID- 28414022
TI - Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell
Carcinoma.
AB - Sunlight is the principal environmental risk factor for keratinocyte cancers, but
other carcinogens have also been implicated, including tobacco smoke. Findings
have been conflicting, however. We investigated associations between cigarette
smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma
(SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history
was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained
through data linkage and verified by histopathology reports. We restricted
analyses to white participants who at baseline reported no past history of skin
cancer excisions and no more than five destructively treated actinic skin
lesions. We fitted Cox proportional hazards models, adjusted for known
confounders. Compared with never smokers, current smokers had significantly lower
risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but
significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval =
1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers.
Among smokers, we observed no dose-response trends with duration of smoking,
intensity, or time since quitting. On further analysis, current smokers had fewer
skin examinations and procedures than never smokers, suggesting greater
opportunities for detection among never smokers. Strengths include large sample
size, prospective design, and virtually complete follow-up; however, histologic
details were missing for a proportion of excised tumors. In conclusion, current
smokers had a lower incidence of BCC (possibly because of detection bias) but
higher rates of SCC.
PMID- 28414023
TI - Effect of spatial and temporal stimulus parameters on the maturation of global
motion perception.
AB - There are discrepancies with respect to the age at which adult-like performance
is reached on tasks assessing global motion perception. This is in part because
performance in children depends on stimulus parameters. We recently showed that
five-year-olds demonstrated adult-like performance over a range of speeds when
the speed ratio was comprised of longer spatial and temporal displacements; but
displayed immature performance when the speed ratio was comprised of shorter
displacements. The goal of the current study was to assess the effect of these
global motion stimulus parameters across a broader age range in order to estimate
the age at which mature performance is reached. Motion coherence thresholds were
assessed in 182 children and adults aged 7-30years. Dot displacement (Deltax) was
1, 5, or 30min of arc; frame duration (Deltat) was 17 or 50ms. This created a
total of six conditions. Consistent with our previous results, coherence
thresholds in the youngest children assessed were adult-like at the two
conditions with the largest Deltax. Maturity was reached around age 12 for the
medium Deltax, and by age 16 for the smallest Deltax. Performance did not appear
to be affected by Deltat. This late maturation may reflect a long developmental
period for cortical networks underlying global motion perception. These findings
resolve many of the discrepancies across previous studies, and should be
considered when using global motion tasks to assess children with atypical
development.
PMID- 28414025
TI - Alterations of the translation apparatus during aging and stress response.
AB - Aging is a biological process characterized by the irreversible and time
dependent deterioration of cell functions, tissues, and organs. Accumulating
studies in a wide range of species from yeast to human revealed changes
associated with the aging process to be conserved throughout evolution. The main
characteristics of aging are (i) genomic instability, (ii) loss of telomere
function, (iii) epigenetic changes,(iv) increased cellular senescence, (v)
depletion of the stem cell pool, (vi) altered intercellular communication and
(vii) loss of protein homeostasis. Among the multiple molecular mechanisms
underlying aging, alterations of the translation machinery affecting the rate and
selectivity of protein biosynthesis seem to play a central role. At the very
heart of translation is the ribosome, a multifaceted and universally conserved
RNA-protein particle responsible for accurate polypeptide synthesis and co
translational protein folding. Here we summarize and discuss recent developments
on the contribution of altered translation and age-dependent modifications on the
ribosome structure to aging and cellular senescence.
PMID- 28414024
TI - Novel high-throughput cell-based hybridoma screening methodology using the Celigo
Image Cytometer.
AB - Hybridoma screening is a critical step for antibody discovery, which necessitates
prompt identification of potential clones from hundreds to thousands of hybridoma
cultures against the desired immunogen. Technical issues associated with ELISA-
and flow cytometry-based screening limit accuracy and diminish high-throughput
capability, increasing time and cost. Conventional ELISA screening with coated
antigen is also impractical for difficult-to-express hydrophobic membrane
antigens or multi-chain protein complexes. Here, we demonstrate novel high
throughput screening methodology employing the Celigo Image Cytometer, which
avoids nonspecific signals by contrasting antibody binding signals directly on
living cells, with and without recombinant antigen expression. The image
cytometry-based high-throughput screening method was optimized by detecting the
binding of hybridoma supernatants to the recombinant antigen CD39 expressed on
Chinese hamster ovary (CHO) cells. Next, the sensitivity of the image cytometer
was demonstrated by serial dilution of purified CD39 antibody. Celigo was used to
measure antibody affinities of commercial and in-house antibodies to membrane
bound CD39. This cell-based screening procedure can be completely accomplished
within one day, significantly improving throughput and efficiency of hybridoma
screening. Furthermore, measuring direct antibody binding to living cells
eliminated both false positive and false negative hits. The image cytometry
method was highly sensitive and versatile, and could detect positive antibody in
supernatants at concentrations as low as ~5ng/mL, with concurrent Kd binding
affinity coefficient determination. We propose that this screening method will
greatly facilitate antibody discovery and screening technologies.
PMID- 28414026
TI - Targeting Oct2 and P53: Formononetin prevents cisplatin-induced acute kidney
injury.
AB - Nephrotoxicity is one of major side effects of cisplatin in chemotherapy.
Therefore, there is an urgent medical need to develop drugs that may protect
kidney from toxicity. In previous study, we found that it showed the protective
effects of formononetin against apoptosis by upregulating Nrf2. In this study, we
investigated the renoprotective effect of formononetin against cisplatin-induced
AKI and tried to elucidate the possible mechanisms. The amelioration of renal
function, histopathological changes, and apoptosis in tubular cells was observed
after formononetin treatment. Formononetin decreased expression of organic cation
transporter 2 (Oct2) and increased the expressions of multidrug resistance
associated proteins (Mrps), which might result in a decrease accumulation of
cisplatin in tubular cells after AKI. 5-Bromo-2-deoxyuridine (BrdU) and Ki-67
staining assay indicated that formononetin could promote the renal tubular cells
proliferation after cisplatin nephrotoxicity. Moreover, formononetin regulated
cyclins and pro-apoptotic proteins to involve the regulation of cell cycle.
Furthermore, formononetin decreased p53 expression via promoting the
overexpression of murine double minute 2 (MDM2) and MDMX. Taken together,
formononetin provided protective effects by promoting proliferation of surviving
renal tubular cells and inhibiting apoptosis after cisplatin-induced AKI.
PMID- 28414027
TI - Arsenic activates the expression of 3beta-HSD in mouse Leydig cells through
repression of histone H3K9 methylation.
AB - Arsenic exposure has been associated with male reproductive dysfunction by
disrupting steroidogenesis; however, the roles of epigenetic drivers, especially
histone methylation in arsenic-induced steroidogenic toxicity remain not well
documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9)
methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to
arsenic exposure. Our results indicated that mRNA and protein expression levels
of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were both significantly up
regulated while the rest of key genes involved in steroidogenesis were down
regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di
and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation
leads to gene activation, we further investigated whether the induction of 3beta
HSD expression was ascribed to reduced H3K9 methylation. The results showed that
H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly
attenuated the decrease of H3K9me2/3 and increase of 3beta-HSD expression induced
by arsenic. To further elucidate the mechanism for the activation of 3beta-HSD,
we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which
also showed significant decrease of H3K9me2/3 in the investigated region after
arsenic exposure. Considering these results, we conclude that arsenic exposure
induced 3beta-HSD up-regulation by suppressing H3K9me2/3 status, which is
suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1
cells.
PMID- 28414028
TI - Culex (Culiciomyia) sasai (Diptera: Culicidae), senior synonym of Cx.
spiculothorax and a new country record for Bhutan.
AB - Culex (Culiciomyia) spiculothorax was described from Thailand based on the
presence of spiculation on the thorax of larvae. Adult females are characterized
but are indistinguishable from those of related species, such as Cx.
pallidothorax. Phylogenetic analysis of mitochondrial oxidase subunit I (COI)
sequences revealed that specimens identified as Cx. spiculothorax from Thailand,
Japan and Bhutan form a single clade with Cx. sasai from Japan (Kimura 2
parameter genetic distances 0-0.9%) that is clearly distinct from clades
comprised of other species of subgenus Culiciomyia. Attempts to collect Cx. sasai
from several locations in Japan were unsuccessful - only larvae with thoracic
vesicular-like spicules identified as Cx. spiculothorax were collected. Careful
examination of specimens collected near the type locality of Cx. sasai revealed
the presence of spicules on the thorax. Based on these findings, Cx.
spiculothorax is formally synonymized with Cx. sasai, which replaces the former
as the species present in Thailand and is a new country record for Bhutan.
PMID- 28414030
TI - POINT: Are Advanced Practice Professionals More Likely to Achieve Better Tobacco
Cessation Results than Physicians? Yes.
PMID- 28414031
TI - Rebuttal From Dr Hitsman et al.
PMID- 28414029
TI - How Well Does CAPTURE Translate?: An Exploratory Analysis of a COPD Case-Finding
Method for Spanish-Speaking Patients.
AB - BACKGROUND: This study tested the properties of a Spanish translation of CAPTURE
(COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and
Exacerbation Risk) with selective use of peak expiratory flow (PEF). METHODS:
This study comprised analyses of data from the Spanish-speaking cohort of the
cross-sectional, case-control study used to develop CAPTURE. Translation
procedures included forward and backward translation, reconciliation, and
cognitive interviewing to assure linguistic and cultural equivalence, yielding
CAPTURE-S. Spanish-speaking participants were recruited through one center and
designated as case subjects (clinically significant COPD: FEV1 <= 60% predicted
and/or at risk of COPD exacerbation) or control subjects (no or mild COPD).
Subjects completed a questionnaire booklet that included 44 candidate items, the
COPD Assessment Test (CAT), and the modified Medical Research Council (mMRC)
dyspnea question. PEF and spirometry were also performed. RESULTS: The study
included 30 participants (17 case subjects and 13 control subjects). Their mean
(+/- SD) age was 62.6 (11.49) years, and 33% were male. CAPTURE-S scores were
significantly correlated with PEF (r = -0.78), the FEV1/FVC ratio (r = -0.74),
FEV1 (r = -0.69), FEV1 % predicted (r = -0.69), the CAT score (r = 0.70), and the
mMRC dyspnea question (r = 0.59) (P < .0001), with significantly higher scores in
case subjects than in control subjects (t = 6.16; P < .0001). PEF significantly
correlated with FEV1 (r = 0.89), FEV1 % predicted (r = 0.79), and the FEV1/FVC
ratio (r = 0.75) (P < .0001), with significantly lower PEF in case subjects than
in control subjects (t = 5.08; P < .0001). CAPTURE-S score + PEF differentiated
case subjects and control subjects with a sensitivity of 88.2% and a specificity
of 92.3%. CONCLUSIONS: CAPTURE-S with selective use of PEF seems to be useful for
identifying Spanish-speaking patients in need of diagnostic evaluation for
clinically significant COPD who may benefit from initiation of COPD treatment.
TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01880177; URL:
www.clinicaltrials.gov.
PMID- 28414032
TI - Rebuttal From Dr Perez et al.
PMID- 28414033
TI - COUNTERPOINT: Are Advanced Practice Professionals More Likely to Achieve Better
Tobacco Cessation Results than Physicians? No.
PMID- 28414034
TI - Age exacerbates surgery-induced cognitive impairment and neuroinflammation in
Sprague-Dawley rats: the role of IL-4.
AB - Age is the most prominent risk factor for the development of postoperative
cognitive dysfunction. This study investigated the potential role of anti
inflammatory interleukin (IL)-4 in age-related differences of surgery-induced
cognitive deficits and neuroinflammatory responses. Both adult and aged Sprague
Dawley male rats were subjected to partial hepatectomy or partial hepatectomy
with a cisterna magna infusion of IL-4. On postoperative days 1, 3, and 7, the
rats were subjected to a reversed Morris water maze test. Hippocampal IL-1beta,
IL-6, IL-4, and IL-4 receptor (IL-4R) were measured at each time point. Brain
derived neurotrophic factor (BDNF), synaptophysin, Ionized calcium-binding
adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, and CD200 were
also examined in the hippocampus. Age induced an exacerbated cognitive impairment
and an amplified neuroinflammatory response triggered by surgical stress on
postoperative days 1 and 3. A corresponding decline in the anti-inflammatory
cytokine IL-4 and BDNF were also found in the aged rats at the same time point.
Treatment with IL-4 downregulated the expression of proinflammatory cytokines
(e.g., IL-1beta and IL-6), increased the levels of BDNF and synaptophysin in the
brain and improved the behavioral performance. An increased Arg1 expression and a
high level of CD200 were also observed after a cisterna magna infusion of IL-4.
An age-related decrease in IL-4 expression exacerbated surgery-induced cognitive
deficits and exaggerated the neuroinflammatory responses. Treatment with IL-4
potentially attenuated these effects by enhancing BDNF and synaptophysin
expression, inhibiting microglia activation and decreasing the associated
production of proinflammatory cytokines.
PMID- 28414035
TI - Bothrops jararaca venom gland secretory cells in culture: Effects of
noradrenaline on toxin production and secretion.
AB - Primary culture of snake venom gland secretory cells could be a good model to
study the mechanism(s) of toxin(s) production. These cells can produce and
secrete venom to the medium with a hemorrhagic activity comparable to that
induced by venom collected from snakes. Production of new venom is triggered by
the sympathetic outflow, through the release of noradrenaline, but the importance
of this neurotransmitter on toxin synthesis has not been addressed. This work led
to the identification and comparison of the toxin panel produced by cultured
secretory cells, during a 12-day time-course analysis, as well as to the effects
of noradrenaline on the process. The results showed that in our culture model the
synthesis of new toxins is asynchronous, mimicking data previously published from
proteomic analyses of venom glands harvested from animal experimentation.
Furthermore, noradrenaline did regulate the synthesis and/or secretion of venom
toxins over the analyzed period. Finally, we demonstrated that snake venom
metalloproteinases present in these cultured cells secretome were mostly in their
zymogen forms; consequently, processing occurs after secretion to the gland
lumen. Overall, the data support the use of venom gland secretory cells as a
reliable model to investigate the mechanism(s) of toxin(s) synthesis and
secretion.
PMID- 28414036
TI - Blunted cortisol response to acute pre-learning stress prevents misinformation
effect in a forced confabulation paradigm.
AB - Research examining the effects of stress on false memory formation has been
equivocal, partly because of the complex nature of stress-memory interactions. A
major factor influencing stress effects on learning is the timing of stress
relative to encoding. Previous work has shown that brief stressors administered
immediately before learning enhance long-term memory. Thus, we predicted that
brief stress immediately before learning would decrease participants'
susceptibility to subsequent misinformation and reduce false memory formation.
Eighty-four male and female participants submerged their hand in ice cold
(stress) or warm (no stress) water for 3min. Immediately afterwards, they viewed
an 8-min excerpt from the Disney movie Looking for Miracles. The next day,
participants were interviewed and asked several questions about the video, some
of which forced them to confabulate responses. Three days and three weeks later,
respectively, participants completed a recognition test in the lab and a free
recall test via email. Our results revealed a robust misinformation effect,
overall, as participants falsely recognized a significant amount of information
that they had confabulated during the interview as having occurred in the
original video. Stress, overall, did not significantly influence this
misinformation effect. However, the misinformation effect was completely absent
in stressed participants who exhibited a blunted cortisol response to the stress,
for both recognition and recall tests. The complete absence of a misinformation
effect in non-responders may lend insight into the interactive roles of autonomic
arousal and corticosteroid levels in false memory development.
PMID- 28414038
TI - Modulation of Staphylococcus epidermidis (RP62A) extracellular polymeric layer by
marine cyclic dipeptide-cyclo(l-leucyl-l-prolyl) thwarts biofilm formation.
AB - Staphylococcus epidermidis is the most frequent cause of biofilm mediated implant
associated infections. Extracellular polymeric substance (EPS) is a key component
of most biofilms and in pathogens it specifically protects the entrenched
bacterial cells from antibiotics and hosts immune response, and thereby makes the
infection ineradicable. Recently, the prominence of cyclic dipeptides in
interfering with biofilms and the associated virulence factors of pathogens has
offered an alternative to eliminate difficult-to-treat infections. Therefore, we
assessed the effect of a potent antibiofilm agent cyclic dipeptide, cyclo(l
leucyl-l-prolyl) (CLP), on the EPS modification of S. epidermidis. The non
bactericidal antibiofilm efficacy of CLP against S. epidermidis was affirmed
through quantitative (crystal violet and XTT assays) and qualitative (confocal
and scanning electron microscopes) analyses. Notably, CLP was potent enough to
reduce all the EPS components viz. polysaccharides, proteins and eDNA to a
significant level. Substantial difference in the atomic composition and
functionality of CLP treated EPS was evident through X-ray photoelectron
spectroscopy. Furthermore, CLP dehydrated the S. epidermidis-EPS and altered the
acetylated sugars as well as alpha-glycosidic linkage in it. The results of
cyclic voltammetry (CV) indicate the decrease of total negative charge of EPS
upon CLP treatment, which goes well in accordance with the decrease of eDNA.
Thus, antibiofilm efficacy of CLP lies in its potency to alter the intrinsic
functional groups and charge of secreted EPS.
PMID- 28414039
TI - Authors' Reply to Rady and Verheijde.
PMID- 28414037
TI - Spatio-temporal regulation of connexin43 phosphorylation and gap junction
dynamics.
AB - Gap junctions are specialized membrane domains containing tens to thousands of
intercellular channels. These channels permit exchange of small molecules
(<1000Da) including ions, amino acids, nucleotides, metabolites and secondary
messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common
reductionist view of these structures is that they are composed entirely of
integral membrane proteins encoded by the 21 member connexin human gene family.
However, it is clear that the normal physiological function of this structure
requires interaction and regulation by a variety of proteins, especially kinases.
Phosphorylation is capable of directly modulating connexin channel function but
the most dramatic effects on gap junction activity occur via the organization of
the gap junction structures themselves. This is a direct result of the short half
life of the primary gap junction protein, connexin, which requires them to be
constantly assembled, remodeled and turned over. The biological consequences of
this remodeling are well illustrated during cardiac ischemia, a process wherein
gap junctions are disassembled and remodeled resulting in arrhythmia and
ultimately heart failure. This article is part of a Special Issue entitled: Gap
Junction Proteins edited by Jean Claude Herve.
PMID- 28414040
TI - SARS coronavirus papain-like protease up-regulates the collagen expression
through non-Samd TGF-beta1 signaling.
AB - SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the
production of TGF-beta1 through p38 MAPK/STAT3-meidated Egr-1-dependent
activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro
induced TGF-beta1 with the expression of Type I collagen in human lung epithelial
cells and mouse pulmonary tissues. Specific inhibitors for TGF-betaRI, p38 MAPK,
MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-beta1-dependent up
regulation of Type I collagen in vitro and in vivo. Subcellular localization
analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-beta1
signaling involved in the production of Type I collagen in transfected cells with
pSARS-PLpro. Comprehensive analysis of ubiquitin-conjugated proteins using
immunoprecipitation and nanoLC-MS/MS indicated that SARS-CoV PLpro caused the
change in the ubiquitination profile of Rho GTPase family proteins, in which
linked with the increase of Rho-like GTPase family proteins. Moreover, selective
inhibitors TGF-betaRI and STAT6 (AS1517499) ascertained that STAT6 activation was
required for PLpro-induced TGF-beta1-dependent up-regulation of Type I collagen
in human lung epithelial cells. The results showed that SARS-CoV PLpro stimulated
TGF-beta1-dependent expression of Type I collagen via activating STAT6 pathway.
PMID- 28414041
TI - Acute and sub-acute toxicological evaluation of lyophilized Nymphaea x rubra
Roxb. ex Andrews rhizome extract.
AB - Nymphaea x rubra Roxb. ex Andrews (N. rubra) has been widely reported for
immunomodulatory properties and treatment of piles, bleeding nose and dysentery
in traditional medicinal systems. However, its in-vitro and in-vivo toxicity
studies have never been investigated. So, the present study was designed to
investigate in-vitro and in-vivo toxicity of methanolic extract of N. rubra
rhizome in rats. In-vitro cytotoxicity studies were conducted for different doses
of extract in N2a cell lines. For in-vivo toxicity studies, SD rats were divided
into three groups and administered with 0, 300 and 2000 mg/kg b. w., p. o., of N.
rubra extract respectively. In acute toxicity studies, female animals after
extract administration animals were sacrificed for hematological profiling and
gross necropsy. In sub-acute toxicity studies, both male and female animals were
administered with extract daily for 14 days and were sacrificed for
hematological, biochemical and histological examination. Body weight and food
water intake was measured daily and animals were observed for visual toxic
effects, behavioral changes and mortality. During in-vivo toxicity studies, none
of the animals showed signs of toxicity and mortality during toxicity studies.
The present findings suggest its safety and NOAEL of N. rubra rhizome extract to
be > 2000 mg/kg b. w.
PMID- 28414042
TI - Promising technological innovations in cognitive training to treat eating-related
behavior.
AB - One potential reason for the suboptimal outcomes of treatments targeting
appetitive behavior, such as eating and alcohol consumption, is that they do not
target the implicit cognitive processes that may be driving these behaviors. Two
groups of related neurocognitive processes that are robustly associated with
dysregulated eating and drinking are attention bias (AB; selective attention to
specific stimuli) and executive function (EF; a set of cognitive control
processes such as inhibitory control, working memory, set shifting, that govern
goal-directed behaviors). An increasing body of work suggests that EF and AB
training programs improve regulation of appetitive behaviors, especially if
trainings are frequent and sustained. However, several key challenges, such as
adherence to the trainings in the long term, and overall potency of the training,
remain. The current manuscript describes five technological innovations that have
the potential to address difficulties related to the effectiveness and
feasibility of EF and AB trainings: (1) deployment of training in the home, (2)
training via smartphone, (3) gamification, (4) virtual reality, and (5)
personalization. The drawbacks of these innovations, as well as areas for future
research, are also discussed. The above-mentioned innovations are likely to be
instrumental in the future empirical work to develop and evaluate effective EF
and AB trainings for appetitive behaviors.
PMID- 28414044
TI - The Impact of the Medicare Access and CHIP Reauthorization Act on the Field of
Ophthalmology.
AB - PURPOSE: To analyze the impact of the Medicare Access and CHIP Reauthorization
Act of 2015 (MACRA) on the field of ophthalmology. DESIGN: A perspective on the
effects of MACRA's Quality Payment Program after analysis of the proposed rule,
final rule, and commentary submitted by relevant stakeholders. RESULTS:
Physicians will need to use 1 of 2 payment structures: Merit-Based Incentive
Payment Systems (MIPS) or Alternative Payment Models (APMs). APMs and MIPS will
focus on bundling payments and reimbursing based on "fee-for-service-plus"
models, which take into account clinical outcomes, coordination of care, clinical
improvement, and electronic information exchange and security. APMs have
substantial advantages, with eligible participants receiving a bonus and a higher
rate of annual adjustment over the program's life. For most ophthalmology
practices, MIPS may be more appropriate owing to its broader applicability and
the current paucity of APMs for ophthalmologists. CONCLUSION: The Quality Payment
Program is a substantial improvement over the negative adjustments under the
repealed Substantial Growth Rate model. Ophthalmologists will likely use the MIPS
system; however, its comparatively lower reimbursements, as well as its cost,
quality, and other reporting measures, may prove problematic.
PMID- 28414043
TI - Quality-of-Life Outcomes From a Randomized Clinical Trial Comparing
Antimetabolites for Intermediate, Posterior, and Panuveitis.
AB - PURPOSE: To evaluate the changes in quality of life in noninfectious uveitis
patients treated with 2 of the most commonly prescribed antimetabolite
treatments. DESIGN: Secondary analysis of a multicenter, block-randomized
clinical trial. METHODS: Eighty patients at Aravind Eye Hospitals in Madurai and
Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were
randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate
mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best
corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and
Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at
enrollment and at 6 months (or prior, in the event of early treatment failure).
RESULTS: IND-VFQ scores, on average, increased by 9.2 points from trial
enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001).
Although the SF-36 physical component summary score did not significantly differ
over the course of the trial, the mental component summary score decreased by 2.3
points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5
points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ
between treatment arms. Linear regression modeling showed a 3.2-point improvement
in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9,
4.3; P < .001). CONCLUSIONS: Although uveitis treatment was associated with
increased vision and vision-related quality of life, patient-reported physical
health did not change after 6 months of treatment, and mental health decreased.
Despite improved visual outcomes, uveitis patients receiving systemic
immunosuppressive therapy may experience a deterioration in mental health-related
quality of life.
PMID- 28414045
TI - Viscosities encountered during the cryopreservation of dimethyl sulphoxide
systems.
AB - This study determined the viscous conditions experienced by cells in the unfrozen
freeze concentrated channels between ice crystals in slow cooling protocols. This
was examined for both the binary Me2SO-water and the ternary Me2SO-NaCl-water
systems. Viscosity increases from 6.9 +/- 0.1 mPa s at -14.4 +/- 0.3 degrees C
to 958 +/- 27 mPa s at -64.3 +/- 0.4 degrees C in the binary system, and up to
55387 +/- 1068 mPa s at -75 +/- 0.5 degrees C in the ternary (10% Me2SO, 0.9%
NaCl by weight) solution were seen. This increase in viscosity limits molecular
diffusion, reducing adsorption onto the crystal plane. These viscosities are
significantly lower than observed in glycerol based systems and so cells in
freeze concentrated channels cooled to between -60 degrees C and -75 degrees C
will reside in a thick fluid not a near-solid state as is often assumed. In
addition, the viscosities experienced during cooling of various Me2SO based
vitrification solutions is determined to below -70 degrees C, as is the impact
which additional solutes exert on viscosity. These data show that additional
solutes in a cryopreservation system cause disproportionate increases in
viscosity. This in turn impacts diffusion rates and mixing abilities of high
concentrations of cryoprotectants, and have applications to understanding the
fundamental cooling responses of cells to Me2SO based cryopreservation solutions.
PMID- 28414046
TI - Caffeoyl and coumaroyl derivatives from Acacia cochliacantha exhibit ovicidal
activity against Haemonchus contortus.
AB - ETHNOPHARMACOLOGY RELEVANCE: Acacia cochliacantha is a small tree whose foliage
is traditionally used in Mexico for treatment of kidney pain, gastrointestinal
illnesses and to kill intestinal parasites. In recent decades, the study of
vegetal extracts has offered other possible alternatives for the control of
Haemonchus contortus. Considering that this nematode affects dramatically the
health and productivity of small ruminants, the aim of this study was to identify
the anthelmintic compounds from A. cochliacantha hydro-alcoholic extract (HA-E)
through an ovicidal test. MATERIAL AND METHODS: In vitro egg hatch assay was
conducted to determinate the anthelmintic effects of a HA-E (60g). Liquid-liquid
ethyl acetate/water extraction gave two fractions (EtOAc-F, 1.92g; Aq-F; 58.1g).
The less polar compounds from ethyl acetate fraction were extracted by addition
of dichloromethane offering a precipitate phase (Mt-F, 1.25g) and a soluble
mixture (DCMt-F 1.15g). All fractions were evaluated for ovicidal activity
obtaining the egg hatching inhibition (EHI, 0.07-25mg/mL). Ivermectin (0.5mg/mL)
was used as a reference drug (positive control), and distilled water, 2.5% DMSO
and 2% methanol were used as negative controls. The isolated compounds from the
most active fractions were subjected to spectroscopic (1H NMR) Spectrometric (MS)
and UV HPLC analysis in order to identify the bioactive compounds. RESULTS: The
less polar treatments (AcOEt-F, DCMt-F, DCMt-P) showed the highest ovicidal
activities (98-100% EHI; at 0.62-1.56mg/mL) and the major compounds found in
these fractions were identified as caffeoyl and coumaroyl derivatives, including
caffeic acid (1), p-coumaric acid (2), ferulic acid (3), methyl caffeate (4),
methyl-p-coumarate (5), methyl ferulate (6) and quercetin. In case of the less
active fractions (Aq-F, Mt-F) were constituted principally by glycosylated
flavonoids. CONCLUSION: These results show that caffeoyl and coumaroyl
derivatives from Acacia cochliacantha leaves had promising anthelmintic activity
against Haemonchus contortus. This leguminous may offer an alternative source for
the control of gastrointestinal nematodes of small ruminants.
PMID- 28414047
TI - A novel automated rodent tracker (ART), demonstrated in a mouse model of
amyotrophic lateral sclerosis.
AB - BACKGROUND: Generating quantitative metrics of rodent locomotion and general
behaviours from video footage is important in behavioural neuroscience studies.
However, there is not yet a free software system that can process large amounts
of video data with minimal user interventions. NEW METHOD: Here we propose a new,
automated rodent tracker (ART) that uses a simple rule-based system to quickly
and robustly track rodent nose and body points, with minimal user input. Tracked
points can then be used to identify behaviours, approximate body size and provide
locomotion metrics, such as speed and distance. RESULTS: ART was demonstrated
here on video recordings of a SOD1 mouse model, of amyotrophic lateral sclerosis,
aged 30, 60, 90 and 120days. Results showed a robust decline in locomotion
speeds, as well as a reduction in object exploration and forward movement, with
an increase in the time spent still. Body size approximations (centroid width),
showed a significant decrease from P30. COMPARISON WITH EXISTING METHOD(S): ART
performed to a very similar accuracy as manual tracking and Ethovision (a
commercially available alternative), with average differences in coordinate
points of 0.6 and 0.8mm, respectively. However, it required much less user
intervention than Ethovision (6 as opposed to 30 mouse clicks) and worked
robustly over more videos. CONCLUSIONS: ART provides an open-source option for
behavioural analysis of rodents, performing to the same standards as commercially
available software. It can be considered a validated, and accessible, alternative
for researchers for whom non-invasive quantification of natural rodent behaviour
is desirable.
PMID- 28414049
TI - Spotlight on vitamin D receptor, lipid metabolism and mitochondria: Some
preliminary emerging issues.
AB - Transcriptional control and modulation of calcium fluxes underpin the
differentiating properties of vitamin D (1,25(OH)2D3). In the latest years
however few studies have pointed out the relevance of the mitochondrial effects
of the hormone. It is now time to focus on the metabolic results of vitamin D
receptor (VDR) action in mitochondria, which can explain the pleiotropic effects
of 1,25(OH)2D3 and may elucidate few contrasting aspects of its activity. The
perturbation of lipid metabolism described in VDR knockout mice and vitamin D
deficient animals can be revisited based on the newly identified mechanism of
action of 1,25(OH)2D3 in mitochondria. From the same point of view, the
controversial role of 1,25(OH)2D3 in adipogenesis can be better interpreted.
PMID- 28414048
TI - Light and the laboratory mouse.
AB - Light exerts widespread effects on physiology and behaviour. As well as the
widely-appreciated role of light in vision, light also plays a critical role in
many non-visual responses, including regulating circadian rhythms, sleep, pupil
constriction, heart rate, hormone release and learning and memory. In mammals,
responses to light are all mediated via retinal photoreceptors, including the
classical rods and cones involved in vision as well as the recently identified
melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs).
Understanding the effects of light on the laboratory mouse therefore depends upon
an appreciation of the physiology of these retinal photoreceptors, including
their differing sens itivities to absolute light levels and wavelengths. The
signals from these photoreceptors are often integrated, with different responses
involving distinct retinal projections, making generalisations challenging.
Furthermore, many commonly used laboratory mouse strains carry mutations that
affect visual or non-visual physiology, ranging from inherited retinal
degeneration to genetic differences in sleep and circadian rhythms. Here we
provide an overview of the visual and non-visual systems before discussing
practical considerations for the use of light for researchers and animal facility
staff working with laboratory mice.
PMID- 28414050
TI - A study of time- and sex-dependent effects of vortioxetine on rat sexual
behavior: Possible roles of direct receptor modulation.
AB - Treatment-related sexual dysfunction is a common side effect of antidepressants
and contributes to patient non-compliance or treatment cessation. However, the
multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in
depressed patients. To investigate the mechanisms involved, sexual behavior was
assessed in male and female rats after acute, and repeated (7 and 14 days)
treatment with vortioxetine, flesinoxan (a 5-HT1A receptor agonist), CP-94253 (a
5-HT1B receptor agonist), or ondansetron (a 5-HT3 receptor antagonist). These
selective ligands were chosen to simulate vortioxetine's direct modulation of
these receptors. Paroxetine was also included in the male study. Acute and
repeated treatment with vortioxetine at doses corresponding to clinical levels
(based on serotonin transporter occupancy) had minimal effects on sexual behavior
in male and female rats. High dose vortioxetine plus flesinoxan (to mimic
predicted clinical levels of 5-HT1A receptor occupancy by vortioxetine)
facilitated male rat sexual behavior (acutely) while inhibiting female rat
proceptive behavior (both acutely and after 14 days treatment). The selective
serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after
repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual
behavior acutely while inhibiting female rat proceptive behavior after repeated
administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male
and female rats after repeated administration. Ondansetron had no effect on
sexual behavior. These findings underline the complex serotonergic regulation of
sexual behavior and indicate that the low sexual side effects of vortioxetine
found in clinical studies are likely associated with its direct modulation of
serotonin receptors.
PMID- 28414052
TI - Spiral MR fingerprinting at 7T with simultaneous B1 estimation.
AB - Magnetic resonance fingerprinting is an efficient, new approach for quantitative
imaging with MR. We aimed to extend this technique to cases with B1+
inhomogeneities within the imaging volume. Previous approaches have used abrupt
changes in flip angles to estimate the B1+ field simultaneously with T1 and T2,
using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated
whether a similar approach would be suitable for imaging human brains using
spiral readouts with a 7T scanner. We found that our modified scheme could
significantly reduce the adverse effects of B1+ inhomogeneities even in extreme
cases, reducing both the bias and the variance in T2 estimations by an order of
magnitude when compared to literature methods. Acquisitions used less than
1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach
can be used to perform quantitative imaging of the brain at 7T in a short time,
simultaneously estimating the B1+ profile.
PMID- 28414051
TI - Mechanisms contributing to cognitive deficits in cannabis users.
AB - Studies from preclinical animal models indicate that sustained activation of CB1
receptor signaling is a major contributing factor for the onset of cognitive
deficits associated to chronic cannabis use, in particular within the working
memory and decision-making domains. Yet, very few studies have been designed to
directly assess the role of CB1 receptors in mediating the effects of cannabis on
human brain function. This perspective review article provides an overview of
current state of knowledge on possible neurobiological mechanisms accounting for
the detrimental effects of chronic cannabis use on cognition and related changes
in brain structure and functional connectivity. This article is part of the
Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".
PMID- 28414053
TI - Inhibition effects of novel polyketide compound PPQ-B against influenza A virus
replication by interfering with the cellular EGFR pathway.
AB - Development of anti-influenza A virus (IAV) drugs with novel targets and low
toxicity is critical for preparedness against influenza outbreaks. In the current
study, our results indicated that the novel polyketide compound purpurquinone B
(PPQ-B) derived from acid-tolerant fungus Penicillium purpurogenum strain JS03-21
suppressed the replication of IAV in vitro with low toxicity, and may block some
stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34;
PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009)
virus replication in vitro, suggesting that PPQ-B possesses broad-spectrum anti
IAV activities. PPQ-B's antiviral activity may be largely related to its
inhibition of some steps that occur 0-4 h after adsorption. Oral administration
of PPQ-B could decrease pulmonary viral titers and improve survival rate in IAV
infected mice. PPQ-B also significantly decreased the production of inflammatory
factors TNF-alpha, IL-6, RANTES and KC in IAV infected lungs and A549 cells,
suggesting that PPQ-B may also attenuate the inflammatory responses caused by IAV
infection. PPQ-B may down-regulate the NF-kappaB and MAPK pathways to inhibit
both virus replication and inflammatory responses. In summary, PPQ-B has the
potential to be developed into a novel anti-IAV drug targeting host EGFR pathway
in the future.
PMID- 28414054
TI - Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal
mammary artery.
AB - The aim of the present study was to investigate and characterize vasorelaxant
effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the
mechanisms of its protective effect against vascular risk. Procyanidin B2 induced
strong concentration-dependent relaxation of HIMA rings pre-contracted by
phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor,
hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate
cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while
indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low
concentrations. Among K+ channel blockers, iberiotoxin, a selective blocker of
large conductance Ca2+-activated K+ channels (BKCa), abolished procyanidin B2
induced relaxation, glibenclamide, a selective ATP-sensitive K+(KATP) channels
blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage
gated K+(KV) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca2+
activated K+(IKCa) channels, slightly reduced maximal relaxation of HIMA.
Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca2+-free
Krebs solution, but had no effect on contraction induced by caffeine. Finally,
thapsigargin, a sarcoplasmic reticulum Ca2+-ATPase inhibitor, significantly
reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate
that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre
contracted by phenylephrine. This effect is primarily the result of an increased
NO synthesis and secretion by endothelial cells and partially of prostacyclin,
although it involves activation of BKCa and KATP, as well as KV and IKCa channels
in high concentrations of procyanidin B2.
PMID- 28414055
TI - Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation
related to inhibitory of oxidative stress.
AB - Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which
showed several pharmacological effects. However, information about the potential
role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation
remains unknown. In the present study, cardiac fibroblasts isolated from neonatal
Sprague-Dawley rats were pretreated with different concentrations of DMY (0
320MUM) for 4h, or DMY (80MUM) for different time (0-24h), followed by Ang II
(100nM) stimulation for 24h, Then number of cardiac fibroblasts and content of
hydroxyproline was measured. The level of cellular reactive oxygen species,
malondialdehyde (MDA), activity of superoxide dismutase (SOD) and total
antioxidant capacity (T-AOC) were also evaluated. Expression of type I, type III
collagen, alpha-smooth muscle actin (alpha-SMA), p22phox (one vital subunit of
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase), SOD and thioredoxin
(Trx) were detected with real time PCR or/and western blot. We found that pre
incubation with DMY (20MUM, 40MUM, 80MUM) for 4h, 12h or 24h attenuated the
proliferation of cardiac fibroblasts induced by Ang II. Expression of type I and
type III collagen, as well as alpha-SMA were inhibited by DMY at both mRNA and
protein level. DMY also significantly decreased cellular reactive oxygen species
production and MDA level, while increased the SOD activity and T-AOC. DMY
suppressed p22phox, while enhanced antioxidant SOD and Trx expression in Ang II
stimulated cardiac fibroblasts. Thus, dihydromyricetin attenuated Ang II induced
cardiac fibroblasts proliferation related to inhibitory of oxidative stress.
PMID- 28414056
TI - Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease
in mice.
AB - Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death
from many diseases. The purpose of the present study is to investigate the
protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on
NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the
mechanisms underlying GA protection. GA treatment significantly reduced the
relative liver weight, serum ALT, AST activities, levels of serum lipid, blood
glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism
investigation indicated that GA reduced hepatic lipogenesis via downregulating
SREBP-1c, FAS and SCD1 expression, increased fatty acids beta-oxidation via an
increase in PPARalpha, CPT1alpha and ACADS, and promoted triglyceride metabolism
through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through
repressing PEPCK and G6Pase, and increased glycogen synthesis through an
induction in gene expression of PDase and GSK3beta. In addition, GA increased
insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In
conclusion, GA produces protective effect against NAFLD, due to regulation of
genes involved in lipid, glucose homeostasis and insulin sensitivity.
PMID- 28414057
TI - Non-invasive assessment of liver fibrosis in patients with HBV-related chronic
liver disease undergoing antiviral treatment: A preliminary study.
AB - In chronic hepatitis B (CHB) patients, fibrosis assessment during antiviral
treatment is a key step in the clinical management. Aim of this study was to
evaluate the performance of elastography in assessing fibrosis stage in CHB
before and after two years of nucleoside/nucleotide analogues (NUC) treatment in
comparison with indirect serum markers. CHB diagnosis was made according to
standard criteria. A clinical and virological evaluation was performed at
baseline and again at 3, 6, 9, 12 18, and 24 months during treatment. Fibrosis
was evaluated by liver biopsy, elastography and indirect serum markers. Of 75
patients, 50 had CHB, HBeAg negative and were deemed eligible for this study. Of
these, 22 underwent liver biopsy. Mean histo-morphometric values of fibrotic
tissue differed significantly in the stage < S3 vs. stage >=S3: 2.01+/-2.62% vs.
12.85+/-7.31% (p=0.03), respectively. At 18 and 24 months, stiffness values were
statistically reduced from those previously observed (P=0.03 and P<0.001). At 24
months the values of APRI, FIB-4 and LOK were not different from baseline values,
while the value of FORNS score at 24 months was the only one statistically
reduced. In two patients with fibrosis stage S3 and S6, respectively, fibrosis
regressed to stage S2 and S5. In conclusion, the results of the present study
show that liver histology, stiffness and FORNS score improve significantly during
a long-term follow-up of HBV patients successfully treated with NUC. These
results strongly suggest that the non-invasive evaluation of liver fibrosis
represents a key step in the management and treatment of chronic HBV hepatitis.
PMID- 28414058
TI - Assessment of bone turnover markers to predict mineral and bone disorder in men
with pre-dialysis non-diabetic chronic kidney disease.
AB - BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances
in mineral metabolism and bone disease. Bone biopsy is the gold standard in
diagnosing mineral bone disorder. Hence the search for non-invasive assessment of
bone health gains importance. We undertook to assess the bone health in men with
stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with
Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25
hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline
phosphatase were assayed. Bone mineral density (BMD) was estimated using dual
energy X-ray absorptiometry. RESULTS: CKD is associated with significantly higher
levels of bone-specific alkaline phosphatase and intact parathyroid hormone and
lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to
controls. In the multivariate linear regression model, bone-specific alkaline
phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator
Characteristic analysis for prediction of reduced BMD in CKD showed both intact
parathyroid hormone and bone-specific alkaline phosphatase have significant
predicting power. CONCLUSION: The combination of bone-specific alkaline
phosphatase and intact parathyroid hormone has more significant predicting power
and is a more reliable index for non-invasive assessment of bone health in men
with chronic kidney disease, than either marker when used alone.
PMID- 28414059
TI - A mouse ocular explant model that enables the study of living optic nerve head
events after acute and chronic intraocular pressure elevation: Focusing on
retinal ganglion cell axons and mitochondria.
AB - We developed an explant model of the mouse eye and optic nerve that facilitates
the study of retinal ganglion cell axons and mitochondria in the living optic
nerve head (ONH) in an ex vivo environment. Two transgenic mouse strains were
used, one expressing yellow fluorescent protein in selected axons and a second
strain expressing cyan fluorescent protein in all mitochondria. We viewed an
explanted mouse eye and optic nerve by laser scanning microscopy at and behind
the ONH, the site of glaucoma injury. Explants from previously untreated mice
were studied with the intraocular pressure (IOP) set artificially at normal or
elevated levels for several hours. Explants were also studied from eyes that had
undergone chronic IOP elevation from 14 h to 6 weeks prior to ex vivo study.
Image analysis in static images and video of individual mitochondria or axonal
structure determined effects of acute and chronic IOP elevation. At normal IOP,
fluorescent axonal structure was stable for up to 3 h under ex vivo conditions.
After chronic IOP elevation, axonal integrity index values indicated
fragmentation of axon structure in the ONH. In mice with fluorescent
mitochondria, the normal density decreased with distance behind the ONH by 45% (p
= 0.002, t-test). Density increased with prior chronic IOP elevation to 21,300 +/
4176 mitochondria/mm2 compared to control 16,110 +/- 3159 mitochondria/mm2 (p =
0.025, t-test), but did not increase significantly after 4 h, acute IOP elevation
(1.5% decrease in density, p = 0.83, t-test). Mean normal mitochondrial length of
2.3 +/- 1.4 MUm became 13% smaller after 4 h of IOP elevation ex vivo compared to
baseline (p = 0.015, t-test, N-10). Normal mitochondrial speed of movement was
significantly slower in the anterograde direction (towards the brain) than
retrograde, but there were more mitochondria in motion and traveling longer
lengths in anterograde direction. The percent of mitochondria in motion decreased
by >50% with acute IOP increase to 30 mm Hg after 60 min. A new ocular explant
model implemented with eyes from transgenic mice with fluorescent cellular
components provided real time measurement of the early events in experimental
glaucoma and quantitative outcomes for neuroprotection therapy experiments.
PMID- 28414060
TI - Dietary protein content alters both male and female contributions to Drosophila
melanogaster female post-mating response traits.
AB - Males transfer sperm, proteins and other molecules to females during mating. In
Drosophila melanogaster, these molecules contribute to the induction of egg
maturation, ovulation, oviposition, sperm storage and changes in female
receptivity. This suite of physiological and behavioral changes is referred to as
the female post-mating response (PMR). Protein is a necessary macronutrient for
both male and female reproduction, but imbalances in protein content can decrease
reproductive potential. Dietary protein affects the production of proteins in the
male ejaculate that are important for induction of the PMR, and female fecundity
increases with dietary protein while lifetime mating rate decreases. The effects
of dietary protein levels on other aspects of the female PMR and on male ability
to induce the PMR are unknown. To investigate how protein content affects PMR, we
raised flies on diets containing low, moderate or high levels of protein and
mated females and males from each diet in a combinatorial manner. We first
measured the mating duration for each pair, an indication of male reproductive
investment, and then evaluated two aspects of the female PMR, fecundity and
female remating latency. We found that mating duration was negatively correlated
with male dietary protein, and females that mated with high protein males laid
fewer eggs. Female diet had no effect on mating duration, but females fed diets
with higher protein content laid more eggs and remated sooner. Therefore, dietary
protein levels can affect postcopulatory processes important for reproductive
output in a sexually dimorphic manner.
PMID- 28414062
TI - Novel PIK3CD mutations affecting N-terminal residues of p110delta cause activated
PI3Kdelta syndrome (APDS) in humans.
PMID- 28414061
TI - Mechanistic correlates of clinical responses to omalizumab in the setting of oral
immunotherapy for milk allergy.
AB - BACKGROUND: In our recent clinical trial, the addition of omalizumab to oral
immunotherapy (OIT) for milk allergy improved safety, but no significant clinical
benefit was detected. OBJECTIVE: We sought to investigate mechanisms by which
omalizumab modulates immunity in the context of OIT and to identify baseline
biomarkers that predict subgroups of patients most likely to benefit from
omalizumab. METHODS: Blood was obtained at baseline and multiple time points
during a placebo-controlled trial of OIT for milk allergy in which subjects were
randomized to receive omalizumab or placebo. Immunologic outcomes included
measurement of basophil CD63 expression and histamine release and casein-specific
CD4+ regulatory T-cell proliferation. Biomarkers were analyzed in relationship to
measurements of safety and efficacy. RESULTS: Milk-induced basophil CD63
expression was transiently reduced in whole blood samples from both omalizumab-
and placebo-treated subjects. However, IgE-dependent histamine release increased
in washed cell preparations from omalizumab- but not placebo-treated subjects. No
increase in regulatory T-cell frequency was evident in either group. Subjects
with lower rates of adverse reactions, regardless of arm, experienced better
clinical outcomes. Pre-OIT basophil reactivity positively associated with
occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio
correlated with the likelihood of achieving sustained unresponsiveness. A
combination of baseline basophil and serologic biomarkers defined a subset of
patients in which adjunctive therapy with omalizumab was associated with
attainment of sustained unresponsiveness and a reduction in adverse reactions.
CONCLUSIONS: Combining omalizumab therapy with milk OIT led to distinct
alterations in basophil reactivity but not T-cell responses. Baseline biomarkers
can identify subjects most likely to benefit from adjunctive therapy with
omalizumab.
PMID- 28414063
TI - Hypersensitivity transfusion reactions due to IgA deficiency are rare according
to French hemovigilance data.
PMID- 28414064
TI - Obesity in coronary heart disease: An unaddressed behavioral risk factor.
AB - Obesity is an independent risk factor for the development and progression of
coronary heart disease (CHD). Over 80% of patients with CHD are overweight or
obese. While obesity is often considered a relatively "minor" CHD risk factor,
weight loss is a broadly effective risk-factor intervention. Weight loss can
profoundly influence a number of "major" risk factors including: hypertension,
dyslipidemia and insulin resistance/type 2 diabetes mellitus. Despite its
prominence as a risk factor most cardiac rehabilitation (CR) programs do not have
a specific, targeted intervention to assist patients with weight loss.
Consequently, the weight loss that occurs during CR is quite small and unlikely
to appreciably alter risk factors. Relying on CR associated exercise as a sole
intervention is an ineffective strategy to promote weight loss. There is
evidence, however, that behavioral weight loss (BWL) interventions can be
effectively employed in the CR setting. In contrast to programs that do not offer
a targeted intervention, studies show that participants in CR-related BWL
programs lose significantly more weight. The additional weight loss from the BWL
intervention is associated with greater improvements in insulin sensitivity and
other components of the metabolic syndrome such as hypertension and lipid
abnormalities. As a means of maximizing CHD risk factor reduction CR programs
need to incorporate BWL programs as a standard programming for overweight/obese
patients.
PMID- 28414065
TI - Effects of depression screening on diagnosing and treating mood disorders among
older adults in office-based primary care outpatient settings: An instrumental
variable analysis.
AB - Existing literature shows mixed findings regarding the efficacy and effectiveness
of depression screening, and relatively little is known about the effectiveness
of depression screening among older adults in primary care visits in the U.S.
This study examines the effects of depression screening on the three following
outcomes: mood disorder diagnoses, overall antidepressant prescriptions, and
potentially inappropriate antidepressant prescriptions among older adults ages 65
or older in office-based outpatient primary care settings. We used data from 2010
2012 National Ambulatory Medical Care Survey (NAMCS), a nationally representative
sample of office-based primary care outpatient visits among older adults (n=9,313
unweighted). We employed an instrumental variable approach to control for
selection bias in our repeated cross-sectional population-based study. Injury
prevention and stress management were selected as instrumental variables, as they
were considered completely exogenous to outcomes of interests using conceptual
and statistical criteria. We conducted multivariate bivariate probit (biprobit)
regression analyses to investigate the effect of depression screening on each
outcome, when controlled for other covariates. We found that depression screening
was negatively associated with potentially inappropriate antidepressant
prescriptions (beta=-2.17; 95% CI -2.80 to -1.53; p<0.001). However, no
significant effect of depression screening on diagnosis of mood disorders and
overall antidepressant prescriptions was found. Overall, depression screening had
a negative effect on potentially inappropriate antidepressant prescriptions.
Primary care physicians and other healthcare providers should actively utilize
depression screening to minimize potentially inappropriate antidepressant
prescriptions in older adult patients.
PMID- 28414066
TI - Factors associated with maintenance of body mass index in the Jackson Heart
Study: A prospective cohort study secondary analysis.
AB - The purpose of this study was to compare the relationship of diet quality,
physical activity, and environmental factors with body mass index (BMI)
maintenance in African American adults. We analyzed data from 4041 participants
in the Jackson Heart Study, a prospective cohort study based in Jackson,
Mississippi. Exposures were baseline American Heart Association diet quality
score, American Heart Association physical activity categories, the built
environment, the food environment, and neighborhood safety. The outcome was
weight maintenance or loss (no BMI increase >=1.0kg/m2) versus weight gain (BMI
increased >=1.0kg/m2) over a mean of 5.0years. We found that 63% of participants
maintained or lost weight and 37% gained weight. In multivariable analyses, ideal
diet quality was associated with a 6% greater likelihood of BMI maintenance
(incidence rate ratio [IRR] 1.06, 95% confidence interval [CI]: 1.03, 1.10).
Living in an unsafe neighborhood was associated with a 2% lower likelihood of BMI
maintenance (IRR 0.98, 95% CI: 0.96, 0.99), as was poor built environment (IRR
0.98, 95% CI: 0.97, 0.998). Physical activity and poor food environment were not
associated with BMI maintenance. In conclusion, among African American adults in
Jackson, Mississippi, high quality diet was the strongest factor associated with
BMI maintenance.
PMID- 28414067
TI - Effective strategies for host cell protein clearance in downstream processing of
monoclonal antibodies and Fc-fusion proteins.
AB - Recombinant therapeutic proteins are typically produced through cell culture
process. Host cell proteins (HCPs) are endogenous proteins derived from the host
cells used for such bioproduction. HCPs form a major class of process-related
impurities and even at low levels they can potentially compromise the safety and
efficacy of biopharmaceuticals. Therefore, they need to be adequately removed via
the downstream process. HCPs are complex mixtures with diverse physiochemical
properties, and certain subpopulations can bind to the intended product. Hence
reducing them to the generally accepted level can be challenging. This article
reviews effective HCP removing strategies at different stages of downstream
process for monoclonal antibodies and Fc-fusion proteins. When used in
combination, these strategies can greatly enhance the chance of meeting the drug
substance specifications for residual HCP.
PMID- 28414068
TI - Modulation of anthraquinones and phloroglucinols biosynthesis in Hypericum spp.
by cryogenic treatment.
AB - Beside the high post-cryogenic recovery rate, a reinstated scale of secondary
metabolites in recovered plant tissues represents another inevitable aspect of an
effective cryopreservation protocol for medicinal plants. The current study was
aimed at evaluation of the elicitation potential of cryogenic treatment on
secondary metabolism of some Hypericum species. In agreement with our assumption,
the cold stimuli applied during the pre-cryogenic phase increased the tolerance
to low temperatures (-196 degrees C) in H. perforatum, H. rumeliacum and H.
tetrapterum reaching a maximum of 46% recovery rate in St. John's wort plants.
The effect of cryogenic treatment-associated stressors on the spectrum of the
profiling secondary metabolites, naphthodianthrones and phloroglucinols, was
ambiguous. The content of hypericins in both pre-cultured H. tetrapterum donor
plants and H. perforatum shoots regenerated from cryopreserved meristems
increased more than 3-times. The highest 38-fold enhancement of phloroglucinols
was observed in H. rumeliacum shoots recovered after cryostorage. Our findings
indicate that modulated biosynthesis of secondary metabolites represented by
naphtodianthrones and phloroglucinols can be considered as a part of overall
plant adaptations to stress conditions associated with liquid nitrogen (LN)
treatment.
PMID- 28414069
TI - Complications associated with antibiotic administration: neurological adverse
events and interference with antiepileptic drugs.
AB - Antibiotic use is associated with toxic effects involving the peripheral and
central nervous systems and it may interfere with antiepileptic drugs, causing
significant variations in their serum levels and activity. Prompt identification
of neurological complications during antibiotic therapy is important in order to
make appropriate modifications to medication. Characteristics of the drug and the
patient, including age and underlying diseases, may favour these complications.
The main aim of this study was to review the neurological adverse events that may
follow antibiotic administration, the mechanisms that cause them, and the
possibility of prevention and treatment. Moreover, the interference of
antibiotics with serum levels and the activity of antiepileptic drugs are
discussed. The results demonstrate that antibiotic-associated adverse events
involving the nervous system are relatively uncommon and are only rarely severe
and irreversible, although neurotoxicity has been reported for several
antibiotics. Moreover, for patients receiving antiepileptic drugs, monitoring of
drug serum levels to avoid the risk of toxicity or inadequate therapy is
mandatory during antibiotic treatment. Areas for future research include the
effects of combined antibiotic therapies as well as multiple antiepileptic drugs
in study populations with an adequate sample size, including neonates and
infants, patients with pharmacoresistant epilepsy and elderly patients.
PMID- 28414070
TI - The unhealthy attraction of Plasmodium vivax to reticulocytes expressing
transferrin receptor 1 (CD71).
AB - The majority of malaria parasite species prefer to invade reticulocytes, the most
infamous being Plasmodium vivax. While the absence of an in vitro continuous
culture method has hampered the study of P. vivax invasion biology, studies
utilising primate models and ex vivo assays have provided some important
insights. Most importantly, P. vivax merozoites have a strong preference for a
subset of immature erythrocytes characterised by the expression of the
transferrin receptor (CD71). This current opinion piece on P. vivax merozoite
invasion highlights important gaps in our understanding of how this parasite
recognises and enters reticulocytes, and discusses some recent conceptual
advances in P. vivax invasion biology.
PMID- 28414071
TI - Epigenetic landscapes underlining global patterns of gene expression in the human
malaria parasite, Plasmodium falciparum.
AB - The dynamic chromatin landscape displaying combinatorial complexity of the
epigenome impacts gene expression that underlies many events of differentiation
and cell cycle progression. In the past few years, epigenetic mechanisms have
emerged as important processes involved in the tight gene regulation in malaria
parasites, Plasmodium spp. Focusing predominantly on Plasmodium falciparum, the
species associated with the most severe form of the disease, many advances have
been made in our understanding of the interaction between transcriptional
regulation and epigenetic mechanisms as the pivotal processes in regulating life
cycle progression, host parasite interactions and parasite adaptation to the host
environment. This review focuses on the epigenome and its effect on
transcriptional regulation in P. falciparum, highlighting its unique,
evolutionary diverse features.
PMID- 28414072
TI - Resistance training is associated with spontaneous changes in aerobic physical
activity but not overall diet quality in adults with prediabetes.
AB - BACKGROUND: Aerobic exercise interventions have been shown to result in
alterations to dietary intake and non-exercise physical activity (PA). To date,
the ability for resistance training (RT) to influence other health-related
behaviors has not been examined. This study aimed to determine if initiation and
maintenance of RT is associated with spontaneous changes in dietary quality and
non-RT PA in adults with prediabetes. METHODS: Overweight/obese adults (n=170,
BMI=32.9+/-3.8kg.m2, age=59.5+/-5.5years, 73% female) with prediabetes were
enrolled in the 15-month Resist Diabetes trial. Participants completed a
supervised 3-month RT initiation phase followed by a 6-month maintenance phase
and a 6-month no-contact phase. Participants were not encouraged to change eating
or non-RT PA behaviors. At baseline, and months 3, 9, and 15, three 24-hour diet
recalls were collected to evaluate dietary intake and quality, the Aerobics
Institute Longitudinal Study Questionnaire was completed to evaluate non-RT PA,
and body mass, body composition (DXA), and muscular strength were measured. At
months 3, 9, and 15 social cognitive theory (SCT) constructs were assessed with a
RT Health Beliefs Questionnaire. Mixed effects models were used to assess changes
in dietary intake and non-RT PA over the 15-month study period. RESULTS: Energy
and carbohydrate intake decreased with RT initiation and maintenance phases
(baseline to month 9: beta=-87.9, p=0.015 and beta=-16.3, p<0.001, respectively).
No change in overall dietary quality (Healthy Eating Index [HEI]-2010 score:
beta=-0.13, p=0.722) occurred, but alterations in HEI-2010 sub-scores were
detected. Maintenance of RT was accompanied by an increase in MET-min/week of
total non-RT PA (month 3 to month 9: beta=146.2, p=0.01), which was predicted by
increased self-regulation and decreased negative outcome expectancies for RT
(beta=83.7, p=0.014 and beta=-70.0, p=0.038, respectively). CONCLUSIONS:
Initiation and maintenance of RT may be a gateway behavior leading to
improvements in other health-related behaviors. These results provide rationale
for single-component lifestyle interventions as an alternative to multi-component
interventions, when resources are limited.
PMID- 28414074
TI - A novel chemotherapy drug-free delivery system composed of three therapeutic
aptamers for the treatment of prostate and breast cancers in vitro and in vivo.
AB - In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three
therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of
cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells
(nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex),
as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA
complex was analyzed by fluorescence imaging and flow cytometry analysis. In the
last step, the presented DNA nanocomplex was applied for prohibition of tumor
growth in vivo. The results of internalization assay verified that the developed
apMNK2F-AS1411-IDA complex was remarkably internalized into PC-3 and 4T1 cells,
but not into CHO cells. The results of internalization assay was confirmed by MTT
assay. apMNK2F-AS1411-IDA complex was more cytotoxic in PC-3 and 4T1 cells
(target) and less cytotoxic in CHO cells (nontarget). Also, the DNA nanocomplex
could effectively suppress the growth of tumors in vivo.
PMID- 28414075
TI - Vitamin B2 deficiency enhances the pro-inflammatory activity of adipocyte,
consequences for insulin resistance and metabolic syndrome development.
AB - AIMS: Adipose tissue is an endocrine organ important for regulation of such
physiological processes as energy metabolism or lipids homeostasis. In an obesity
state, it participates in the induction of chronic systemic inflammation
accompanied by pro-inflammatory cytokines and fatty acid elevation. For this
reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes
or hyperlipidemia development. In our previous study, we have shown that
riboflavin deficiency induces a pathological pro-inflammatory response of
macrophages, the main component of adipose tissue. Therefore, in the current
study, we investigated the alteration of the pro-inflammatory activity of
adipocytes. MAIN METHODS: The study was conducted on mouse 3T3 L1 preadipocytes
differentiated to adipocyte and culture in the state of riboflavin deficiency
(3.1nM) or control condition (10.4nM). The cell viability, adiposity and glucose
uptake was assessed. Moreover, mRNA expression, as well as crucial pro
inflammatory cytokines (TNFalpha, IL-6) and adipokines (adiponectin, leptin,
resistin) release and NFkappaB activation, were evaluated. KEY FINDINGS: Results
showed that riboflavin deprivation induced a significant elevation in adipocyte
lipolysis and enhance obesity-related apoptosis of adipocytes. The generation of
reactive oxygen species was enhanced in riboflavin-deficient adipocytes by 43%.
Moreover, NFkappaB phosphorylation and the expression and release of both
TNFalpha, IL-6 as well as leptin were elevated in a deficient group what was
accompanied by a reduction of adiponectin level. CONCLUSION: Our study shows that
riboflavin deficiency can promote the intensification of pro-inflammatory
activity of adipocyte cells, leading consequently to the severity of chronic
inflammation that accompanies obesity state.
PMID- 28414073
TI - Metabolic and affective consequences of fatherhood in male California mice.
AB - Physiological and affective condition can be modulated by the social environment
and parental state in mammals. However, in species in which males assist with
rearing offspring, the metabolic and affective effects of pair bonding and
fatherhood on males have rarely been explored. In this study we tested the
hypothesis that fathers, like mothers, experience energetic costs as well as
behavioral and affective changes (e.g., depression, anxiety) associated with
parenthood. We tested this hypothesis in the monogamous, biparental California
mouse (Peromyscus californicus). Food intake, blood glucose and lipid levels,
blood insulin and leptin levels, body composition, pain sensitivity, and
depression-like behavior were compared in males from three reproductive groups:
virgin males (VM, housed with another male), non-breeding males (NB, housed with
a tubally ligated female), and breeding males (BM, housed with a female and their
first litter). We found statistically significant (P<0.007, when modified for
Adaptive False Discovery Rate) or nominally significant (0.00790% of B. fragilis, non-fragilis Bacteroides and Parabacteroides
isolates. With the exception of B. fragilis division II, imipenem was active
against 88.0%-98.3% of isolates of the other species. Susceptibility rates for
clindamycin (14.4%-54.3%) and moxifloxacin (33.3%-80.6%) were low across all
species and many isolates had no inhibition zone around the discs. E-test testing
confirmed 8.2% (61/741) and 1.6% (12/741) isolates as nonsusceptible to imipenem
and metronidazole, respectively with B. fragilis and B. thetaoiotaomicron
accounting for a large share of the observed resistance to both agents. Two
imipenem-resistant and one metronidazole-resistant B. dorei were misidentified as
B. vulgatus by MALDI-TOF MS. These data highlights the importance anaerobic
susceptibility testing in clinical laboratories to guide therapy.
PMID- 28414108
TI - Improvingthecatalytic properties and stability of immobilized gamma
glutamyltranspeptidase by post-immobilization with PharmalyteMT 8-10.5.
AB - gamma-Glutamyltranspeptidase (GGT) is a dimeric protein that specifically
catalyzes the transfer of gamma-glutamyl in the optimum pH range of 8.5-9.0, but
has poor in vitro stability under the alkaline conditions. In the present work,
GGT was immobilized on a mesoporoustitania oxide whisker (MTWs) carrier to afford
MTWs-GGT that was further modified with PharmalyteMT (Phar) 8.0-10.5 to yield
MTWs-GGT-Phar. Phar absorbed on MTWs-GGT to form a buffering layer with an
isoelectric point of ~9.2 that isolated the immobilized enzyme from the liquid
bulk and significantly in proved the pH tolerance and stability of the
immobilized GGT. The MTWs-GGT-Phar exhibited a stable enzyme activity in the pH
range of 6.0-11.0 and an optimum temperature 10 degrees C higher than GGT. Its pH
stability at pH 11.0 and thermal stability at 50 degrees C were respectively 23.7
times and 19.4 times higher than those of GGT. In addition, the affinity constant
of MTWs-GGT-Phar towards GpNA (Km) was 0.597mM, slightly lower than that of free
GGT, indicating that Phar had a protective effect on the structure of GGT.
PMID- 28414109
TI - Synthesis and characterization of chitosan nanoparticles and their effect on
Fusarium head blight and oxidative activity in wheat.
AB - The main aim of present study was to prepare chitosan (CS) and chitosan
nanoparticles (CS/NPs) to evaluate their antifungal and oxidative activity.
CS/NPs were prepared based on the ionic gelation of CS with tripolyphosphate
(TPP) anions by using centrifugation and pH change. The obtained nanoparticles
(NPs) were characterized by size and zeta potential analysis. The antifungal
activity of the CS and CS/NPs were evaluated on the Fusarium graminearum, which
causes Fusarium head blight (FHB) on wheat by the method of spraying on the
Potato dextrose agar (PDA) medium. The Dynamic light scattering (DLS) indicated
that particle diameter (z-average) was approximately 180.9+/-35.5-339.4+/-50.9
and 225.7+/-42.81-595.7+/-81.7nm for NPs prepared from CS with different
molecular weights by using centrifugation and pH change methods, respectively.
Different concentrations of CS and NPs were tested to know the inhibitory effect
of F. graminearum. Low molecular weight (LMW) CS and its NPs had high potential
of antifungal activity on suppress of fungus growth. The maximum percentage of
growth reduction was 68.18%, and 77.5% by CS and its NPs at concentrations of
1000 and 5000ppm, respectively. In greenhouse trials, at 28days after inoculation
(dpi), the area under the disease progress curve (AUDPC) from 7 dpi to 28 dpi of
control plants treated with acetic acid aqueous solution and distilled water was
almost up to 7.36 and 7.7, respectively, while plants treated with CS and NPs
only had approximately 3.61 and 3.34, respectively. Results revealed that H2O2
accumulations displayed a different pattern during the activation of plant
defense systems, it had brownish sites on the infected palea. Since 24h post
inoculation (hpi), the H2O2 accumulations were shown in both CS and NPs, and the
elevated H2O2 accumulation appeared in 72 hpi in both treatments. CS and NPs at
high concentration increased the degree of tissue and cell injury. The obtained
results clearly suggest that CS and its NPs have remarkable potential for further
field screening towards crop protection.
PMID- 28414110
TI - Rifampicin as a novel tyrosinase inhibitor: Inhibitory activity and mechanism.
AB - In this study, the inhibitory effect and mechanism of rifampicin on the activity
of tyrosinase were investigated for developing a novel tyrosinase inhibitor. It
was found to have a significant inhibition on the activity of tyrosinase
(IC50=90+/-0.6MUM). From the kinetics analysis, it was proved to be a reversible
and noncompetitive type inhibitor of the enzyme with the KI value of 94+/-3.5MUM.
The results obtained from intrinsic fluorescence quenching indicated that
rifampicin could interact with tyrosinase. In particular, the drastic decrease of
fluorescence intensity was due to the formation of a rifampicin-enzyme complex in
a static procedure which was mainly driven by hydrophobic forces and hydrogen
bonding. Moreover, the ANS-binding fluorescence analysis suggested that
rifampicin binding to tyrosinase changed the polarity of the hydrophobic regions.
Molecular docking analysis further revealed that the hydrogen bonds were
generated between rifampicin and amino residues Leu7, Ser52, and Glu107 in the B
chain of the enzyme. And the hydrophobic forces produced through the interaction
of rifampicin with B chain residues Pro9, Pro14, and Trp106. This work identified
a novel tyrosinase inhibitor and potentially contributed to the usage of
rifampicin as a potential hyperpigmentation drug.
PMID- 28414111
TI - Screening for the best detergent for the isolation of placental membrane
proteins.
AB - Although membrane proteins (MPs) play crucial roles in physiological processes,
information on them are insufficient, mostly due to their peculiar nature and
surrounding which demand specific procedures for their extraction (using
detergents) and analysis. A pallet of ten detergents and beta-cyclodextrin was
employed to investigate their efficiency in extracting total placental MPs,
glycoproteins and insulin-like growth factor receptors (IR/IGF1R/IGF2R).
Regardless of detergent used, the identity of major extracted proteins was the
same. Glycoproteins extracted with Triton X-100 contained the greatest variety
and quantity of glycans recognised by fifteen lectins, pointing to this detergent
as universal medium for the extraction of membrane glycoproteins. Glycoproteins
extracted using Brij 35 exhibited weak interaction with only seven lectins and
were differently recognised by lectins of the similar glycan specificity. Brij
35, Tween 20, saponin and digitonin selectively extracted IGF2R compared to other
two receptors. Pilot experiments should be conducted in order to choose adequate
detergent for the extraction of specific MP. To obtain preparations enriched in
specific receptor of the insulin/IGF system sequential solubilisation of
placental MPs can be proposed: to use Brij 35 to extract IGF2R and subject the
insoluble remaining suspension to Triton X-114 in order to extract most of IGF1R
with small amounts of IR.
PMID- 28414112
TI - Binding of erucic acid with human serum albumin using a spectroscopic and
molecular docking study.
AB - Erucic acid (EA) is one of the key fatty acids usually found in canola oil,
mustard oil and rapeseed oil. Consumption of EA in primates was found to cause
myocardial lipidosis and cardiac steatosis. To have an insight of the effect of
EA in humans, we performed in vitro interaction studies of EA with the primary
plasma protein, human serum albumin (HSA). Spectroscopic (UV-vis and
fluorescence) analysis of the HSA-EA interaction revealed a static mode of
quenching with binding constant Kb ~104 reflecting high affinity of EA for HSA.
The negative value of DeltaG degrees for binding of EA to HSA in the
fluorescence studies indicates the process to be spontaneous. Thermodynamic
signatures of the HSA-EA interaction in the complex reflect dominance of hydrogen
bonds. Despite predominance of hydrogen bonds, hydrophobic interactions in the
HSA-EA complex were found acting as a contributing factor in the binding of EA to
HSA, observed as structural change in the far-UV CD spectra. Forster's resonance
energy transfer of the EA-HSA complex revealed a distance of 3.2nm between
acceptor molecules (EA) and the donor Trp residue of HSA. To have a deeper
insight of the structural dependence of the HSA-EA interaction in the complex,
thermodynamic study was supplemented with molecular docking. The molecular
docking analysis further highlighted the EA binding in the subdomain IIIA (Sudlow
site II) of HSA. The information generated in the study reflects greater
pharmacological significance of EA and highlights its importance in the clinical
medicine.
PMID- 28414113
TI - sept8a and sept8b mRNA expression in the developing and adult zebrafish.
AB - Septins are highly conserved GTP-binding proteins involved in numerous cellular
processes. Despite a growing awareness of their roles in the cell biology,
development and signal transmission in nervous systems, comparably little is
known about precise septin expression. Here, we use the well-established model
organism zebrafish (Danio rerio) to unravel the expression of sept8a and sept8b,
with special focus on the CNS. We performed whole mount RNA in situ hybridization
on zebrafish 1-4 dpf in combination with serial sectioning of epon-embedded
samples as well as on brain sections of adult zebrafish to obtain precise
histological mapping of gene expression. Our results show a common expression of
both genes at embryonic stages, whereas sept8a is mainly restricted to the gill
arches and sept8b to specific brain structures at later stages. Brains of adult
zebrafish reveal a large spatial overlap of sept8a and sept8b expression with few
regions uniquely expressing sept8a or sept8b. Our results indicate a neuronal
expression of both genes, and additionally suggest expression of sept8b in glial
cells. Altogether, this study provides a first detailed insight into the
expression of sept8a and sept8b in zebrafish and contributes to a more
comprehensive understanding of septin biology in vertebrate model systems.
PMID- 28414114
TI - Why Do Long-Distance Travelers Have Improved Pancreatectomy Outcomes?
AB - BACKGROUND: Centralization of complex surgical care has led patients to travel
longer distances. Emerging evidence suggested a negative association between
increased travel distance and mortality after pancreatectomy. However, the reason
for this association remains largely unknown. We sought to unravel the
relationships among travel distance, receiving pancreatectomy at high-volume
hospitals, delayed surgery, and operative outcomes. STUDY DESIGN: We identified
44,476 patients who underwent pancreatectomy for neoplasms between 2004 and 2013
at the reporting facility from the National Cancer Database. Multivariable
analyses were performed to examine the independent relationships between
increments in travel distance mortality (30-day and long-term survival) after
adjusting for patient demographics, comorbidity, cancer stage, and time trend. We
then examined how additional adjustment of procedure volume affected this
relationship overall and among rural patients. RESULTS: Median travel distance to
undergo pancreatectomy increased from 16.5 to 18.7 miles (p for trend < 0.001).
Although longer travel distance was associated with delayed pancreatectomy, it
was also related to higher odds of receiving pancreatectomy at a high-volume
hospital and lower postoperative mortality. In multivariable analysis, difference
in mortality among patients with varying travel distance was attenuated by
adjustment for procedure volume. However, longest travel distance was still
associated with a 77% lower 30-day mortality rate than shortest travel among
rural patients, even when accounting for procedure volume. CONCLUSIONS: Our large
national study found that the beneficial effect of longer travel distance on
mortality after pancreatectomy is mainly attributable to increase in procedure
volume. However, it can have additional benefits on rural patients that are not
explained by volume. Distance can represent a surrogate for rural populations.
PMID- 28414115
TI - Cost Analysis of a Surgical Consensus Guideline in Breast-Conserving Surgery.
AB - BACKGROUND: The Society of Surgical Oncology and American Society of Radiation
Oncology consensus statement was the first professional guideline in breast
oncology to declare "no ink on tumor" as a negative margin in patients with
stages I/II breast cancer undergoing breast-conservation therapy. We sought to
analyze the financial impact of this guideline at our institution using a
historic cohort. STUDY DESIGN: We identified women undergoing re-excision after
breast-conserving surgery for invasive breast cancer from 2010 through 2013 using
a prospectively maintained institutional database. Clinical and billing data were
extracted from the medical record and from administrative resources using CPT
codes. Descriptive statistics were used in data analysis. RESULTS: Of 254 women
in the study population, 238 (93.7%) had stage I/II disease and 182 (71.7%) had
invasive disease with ductal carcinoma in situ. A subcohort of 83 patients
(32.7%) who underwent breast-conservation therapy for stage I/II disease without
neoadjuvant chemotherapy had negative margins after the index procedure, per the
Society of Surgical Oncology and American Society of Radiation Oncology
guideline. The majority had invasive ductal carcinoma (n = 70 [84.3%]) and had
invasive disease (n = 45 [54.2%]), and/or ductal carcinoma in situ (n = 49
[59.0%]) within 1 mm of the specimen margin. Seventy-nine patients underwent 1 re
excision and 4 patients underwent 2 re-excisions, accounting for 81 hours of
operative time. Considering facility fees and primary surgeon billing alone, the
overall estimated cost reduction would have been $195,919, or $2,360 per affected
patient, under the guideline recommendations. CONCLUSIONS: Implementation of the
Society of Surgical Oncology and American Society of Radiation Oncology consensus
guideline holds great potential to optimize resource use. Application of the
guideline to a retrospective cohort at our institution would have decreased the
overall re-excision rate by 5.6% and reduced costs by nearly $200,000. Additional
analysis of patient outcomes and margin assessment methods is needed to define
the long-term impact on surgical practice.
PMID- 28414117
TI - Global Surgery: Lifeline for the US Military Surgeon.
PMID- 28414116
TI - The Largest European Single-Center Experience: 300 Laparoscopic Pancreatic
Resections.
AB - BACKGROUND: Although laparoscopic pancreatic resection (LPR) has become routine,
large single-center series are still lacking. Our aim was to analyze the results
of a large European single-center series of LPR. STUDY DESIGN: Between January
2008 and September 2015, 300 LPRs were performed and studied prospectively,
including 165 (55%) distal pancreatectomies, 68 (23%) pancreaticoduodenectomies
(PDs), 30 (10%) enucleations, 35 (11%) central pancreatectomies, and 2 (1%) total
pancreatectomies. RESULTS: Mean age was 54 +/- 15.4 years old (range 17 to 87
years), and most patients were women (58%). Laparoscopic pancreatic resection was
performed for malignancy (46%), low potential malignant (44%), or benign (10%)
diseases. The mean operative durations were 211 +/- 102 minutes (range 30 to 540
minutes) for the entire population and 351 +/- 59 minutes (range 240 to 540
minutes) for PD, and decreased with the learning curve. Mean blood loss was 229
+/- 269 mL (range 0 to 1,500 mL), and 13 patients (4%) received transfusions.
Conversion to an open procedure was required in 12 patients (4%), and only 5 in
the last 250 patients (14% vs 2%; p < 0.001). Mortality occurred in 4 (1.3%)
patients and only after PD (5.8%). Common complications were pancreatic fistula
(n = 124, 41%), bleeding (n = 35, 12%), and reoperation (n = 28, 9%). The
postoperative outcomes were less favorable in procedures with a reconstruction
phase (n = 105) than in those without (n = 195), with increased mortality (3.8%
vs 0%; p = 0.04), overall morbidity (76% vs % 52%; p < 0.001), and mean hospital
stay (26 +/- 15 days vs 16 +/- 10 days; p < 0.001). CONCLUSIONS: Laparoscopic
pancreatic resection without a reconstruction phase has excellent outcomes; LPR
with a reconstruction phase, especially PD, has less favorable outcomes, and
further randomized studies are required to draw conclusions on the safety and
benefits of this approach.
PMID- 28414118
TI - Comparing existing classifications of fistula-in-ano in 440 operated patients: Is
it time for a new classification? A Retrospective Cohort Study.
AB - BACKGROUND: Fistula-in-ano are classified so as to grade them according to
increasing complexity which can help guide their management. The classifications
used are Parks, St James Hospital University (SJHU) and Standard Practice Task
Force (SPTF). Laying open (fistulotomy) of the fistula tract is the most commonly
done procedure for fistula-in-ano and has high success rate. The lower grade
fistulas are supposed to have low risk of incontinence when laid open and vice
versa. The objective of the study was to evaluate the efficacy of the existing
classifications. MATERIALS & METHODS: 440 consecutive fistula-in-ano patients
operated over four years were analyzed on the basis of preoperative MRI scan and
operative findings. It was assessed whether the amenability to fistulotomy
(measurement of fistula simplicity) correlated with the fistula-in-ano grades in
different classifications. RESULTS: Out of 440 patients operated, 242 underwent
fistulotomy whereas 198 underwent sphincter-sparing procedures for complex
fistula. As per SJHU classification, the amenability to fistulotomy was 99.1% in
Grade-I, 82.1% in Grade-II, 46.2% in Grade-III, 29.0% in Grade-IV and 5.4% in
Grade-V. In Park's classification, the amenability to fistulotomy was 93.5% in
Grade-I, 34.8% in Grade-II, 5.4% in Grade-III and 0% in Grade-IV. As per SPTF
classification, 99.3% of simple and 32.1% of complex fistulas underwent
fistulotomy. Even the higher grade fistula-in-ano in all three classifications
had high rate of amenability to fistulotomy. Therefore none of the above
classifications were accurate. A new classification is being proposed which
divides fistula-in-ano in 5 grades in order of increasing complexity. Grade I &
II are simple fistulas (fistulotomy be done conveniently) and Grade III-V are
high complex fistulas (fistulotomy should not be attempted). The data was
analyzed as per new classification and found it to be highly accurate.
CONCLUSIONS: None of the existing classifications accurately correlated between
the grade and the complexity of fistula. A new classification is being proposed.
PMID- 28414119
TI - Efficacy of the fissureless technique on decreasing the incidence of prolonged
air leak after pulmonary lobectomy: A systematic review and meta-analysis.
AB - OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of
fissureless technique in pulmonary lobectomy by applying a meta-analysis of the
current evidence. METHODS: We searched the PubMed, EMBASE and the Web of Science
databases to recognize the eligible articles. The relative risk (RR) and weighted
mean difference (WMD) with the corresponding 95% confidence interval (CI) served
as the summarized estimates for dichotomous variables and continuous variables,
respectively. Sensitivity analysis and publication bias tests were also performed
to perceive potential bias risks. RESULTS: There were 6 studies with 843 surgical
patients included into this meta-analysis. Finally, the meta-analysis
demonstrated that fissureless technique could significantly reduce the incidence
of prolonged air leak (PAL)[RR = 0.40; 95%CI=(0.24, 0.68); P = 0.001], the length
of hospital stay [WMD = -0.52; 95%CI=(-0.87, -0.18); P = 0.003] and the duration
of chest tube [WMD = -0.44; 95%CI=(-0.74, -0.14); P = 0.004]. Fissureless
technique had also showed the benefit on decreasing the complication rate after
lobectomy but without a statistical significance [RR = 0.77; 95%CI=(0.55, 1.07);
P = 0.119]. In addition, no difference was observed in the operation time between
the fissureless lobectomy and conventional lobectomy [WMD = 5.32; 95%CI=(-3.18,
13.83); P = 0.220]. CONCLUSIONS: Fissureless lobectomy is a superior alternative
to conventional lobectomy in terms of preventing the PAL and shortening the
length of hospital stay and chest tube duration. More multi-institution
randomized controlled trials are required to confirm the validity of our findings
in the future.
PMID- 28414120
TI - The predictive value of integrated inflammation scores in the survival of
patients with resected hepatocellular carcinoma: A Retrospective Cohort Study.
AB - BACKGROUND: Evidence supports the predictive potential of inflammatory marker
derived scores (inflammation scores) and hepatitis B virus (HBV) infection on
prognosis of patients with hepatocellular carcinoma (HCC). However, no study has
longitudinally assessed the predictive values of inflammation scores combined
with hepatitis B virus status on survival of these patients. Therefore, a study
was designed to evaluate the prognostic capacity of preoperative, dynamic changes
in integrated scores, through a combination of general inflammation scores and
HBV infection status, on HCC patients undergoing tumor resection. METHODS: The
clinicopathological data of 247 patients with primary HCC who underwent liver
resection were collected. Inflammation-related laboratory examinations were
performed 1 week before operation, and 1 week, 1 month, 3months, and 6months
after operation. The prognostic values of preoperative and dynamic changes in
integrated inflammation scores were studied using the Cox regression models.
RESULTS: Elevated preoperative integrated inflammation scores, including co
Glasgow prognostic score (coGPS), co-modified Glasgow prognostic score (comGPS),
co-C reactive protein to albumin ratio (coCRP/ALB), co-prognostic index (coPI),
co-neutrophil to lymphocyte ratio (coNLR), co-lymphocyte to monocyte ratio
(coLMR), coNLR-PLR and coCRP/ALB-PLR, were associated with decreased overall
survival (OS). Dynamic changes in coGPS, comGPS, coCRP/ALB, coPI, coPLR, coNLR,
coSII, coNLR-PLR, and coCRP/ALB-PLR were independent prognostic factors of OS.
coCRP/ALB-PLR was significantly associated with disease free survival.
CONCLUSIONS: Preoperative and dynamic changes in integrated inflammation scores,
particularly for coCRP/ALB-PLR were important and stable prognostic markers in
HCC.
PMID- 28414121
TI - Neural-derived estradiol regulates brain plasticity.
AB - In addition to be an ovarian hormone, estradiol is a neurosteroid synthesized by
neural cells. The brain is a steroidogenic tissue that metabolizes testosterone
to estradiol. The last step in the synthesis of estradiol is catalyzed by the
enzyme aromatase, which is widely expressed in the brain of male and female
animals and humans. Studies that have manipulated the expression or the activity
of aromatase have revealed that brain-derived estradiol acts as a neuromodulator
and regulates different forms of brain plasticity in male and female animals. The
regulation of neuroplastic events by brain-derived estradiol probably
participates in the effects of brain aromatase on behavior and cognition.
PMID- 28414122
TI - RIFM fragrance ingredient safety assessment, isononyl propionate, CAS Registry
Number 65155-45-5.
PMID- 28414123
TI - Anti-factor Xa activities of zingerone with anti-platelet aggregation activity.
AB - Zingerone (ZGR), a phenolic alkanone found in Zingiber officinale, has been
reported to have various pharmacological activities such as anti-inflammatory,
anti-apoptotic, and protecting myocardial infarction and irritable bowel
disorder. The aim was to identify the unreported bioactive anti-factor Xa (FXa)
and anti-platelet activities of ZGR. ZGR was evaluated for their anti-FXa and
anti-platelet aggregation properties by monitoring clotting time, platelet
aggregation, FXa activity and production, and thrombus formation. ZGR reduced
activated partial thromboplastin time and it inhibited the catalytic activity of
FXa toward its substrate S-2222 in a noncompetitive inhibition model and
inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619
(not thrombin). However, ZGR did not prolong bleeding time in mice, as shown by
tail clipping. ZGR also inhibited ADP- and U46619- induced phosphorylation of
myristolated alanine-rich C-kinase substrate (MARCKS) and the expressions of P
selectin and PAC-1 in platelets. In an animal model of arterial and pulmonary
thrombosis, ZGR showed enhanced antithrombotic effects. ZGR also elicited
anticoagulant effects in mice. Our results reveal that ZGR is an antithrombotic
compound with both FXa inhibitory and anti-platelet aggregation activities.
Collectively, these results show that ZGR could serve as candidates and provide
scaffolds for the development of new anti-FXa and anti-platelet drugs.
PMID- 28414124
TI - Roles of piRNAs in microcystin-leucine-arginine (MC-LR) induced reproductive
toxicity in testis on male offspring.
AB - In the present study, we evaluated the toxic effects on the testis of the male
offspring of MC-LR exposure during fetal and lactational periods. Pregnant
females were distributed into two experimental groups: control group and MC-LR
group which were exposed to 0 and 10 MUg/L of MC-LR, respectively, through
drinking water separately during fetal and lactational periods. At the age of 30
days after birth, the male offspring were euthanized. The body weight, testis
index, and histomorphology change were observed and the global changes of piwi
interacting RNA (piRNA) expression were evaluated. The results revealed that MC
LR was found in the testis of male offspring, body weight and testis index
decreased significantly, and testicular tissue structure was damaged in the MC-LR
group. In addition, the exposure to MC-LR resulted in an altered piRNA expression
profile and an increase of the cell apoptosis and a decrease of the cell
proliferation in the testis of the male offspring. It was reasonable to speculate
that the toxic effects on reproductive system of the male offspring in MC-LR
group might be mediated by piRNAs through the regulation of the target genes. As
far as we are aware, this is the first report showing that MC-LR could play a
role in disorder of proliferative and cell apoptosis in the testis of the male
offspring by the maternal transmission effect of toxicity.
PMID- 28414125
TI - The number of the C-terminal transmembrane domains has the potency to specify
subcellular localization of Sec22c.
AB - Sec22c has been characterized as an endoplasmic reticulum (ER)-localized
transmembrane protein involved in regulation of the vesicle transport between the
ER and the Golgi. Sec22c has several isoforms generated by alternative splicing
that changes the number of the C-terminal transmembrane domains (TMDs). However,
the physiological significance of the splicing remains unknown. Here we show that
the splicing isoforms containing four TMDs unexpectedly localized at cis-Golgi,
whereas the splicing isoforms containing less than four TMDs localized at the ER.
The C-terminal fragment containing the four TMDs was sufficient for the cis-Golgi
localization and bound to ADP-ribosylation factor 4 (ARF4). ARF4 knockdown and
overexpression of a constitutively active mutant of ARF4 decreased the cis-Golgi
localization of the C-terminal fragment and the full-length protein,
respectively. These results indicate that the splicing-dependent changes in the
number of TMDs allow Sec22c to regulate the subcellular localization in
cooperation with ARF4, implying that Sec22c will function at the Golgi as well as
the ER.
PMID- 28414126
TI - Characterization of the novel protein KIAA0564 (Von Willebrand Domain-containing
Protein 8).
AB - The VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564.
Based on the observation, by similarity, that the protein encoded by KIAA0564
contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand
Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost
unknown. The purpose of this study was to characterize the tissue distribution,
cellular location, and function of VWA8. In mice VWA8 protein was mostly
distributed in liver, kidney, heart, pancreas and skeletal muscle, and is present
as a long isoform and a shorter splice variant (VWA8a and VWA8b). VWA8 protein
and mRNA were elevated in mouse liver in response to high fat feeding. Sequence
analysis suggests that VWA8 has a mitochondrial targeting sequence and domains
responsible for ATPase activity. VWA8 protein was targeted exclusively to
mitochondria in mouse AML12 liver cells, and this was prevented by deletion of
the targeting sequence. Moreover, the VWA8 short isoform overexpressed in insect
cells using a baculovirus construct had in vitro ATPase activity. Deletion of the
Walker A motif or Walker B motif in VWA8 mostly blocked ATPase activity,
suggesting Walker A motif or Walker B motif are essential to the ATPase activity
of VWA8. Finally, homology modeling suggested that VWA8 may have a structure most
confidently similar to dynein motor proteins.
PMID- 28414127
TI - Crystal structure of the flagellar chaperone FliS from Bacillus cereus and an
invariant proline critical for FliS dimerization and flagellin recognition.
AB - FliS is a cytoplasmic flagellar chaperone for the flagellin, which polymerizes
into filaments outside of the flagellated bacteria. Cytoplasmic interaction
between FliS and flagellin is critical to retain the flagellin protein in a
monomeric form, which is transported from the cytoplasm through the flagellar
export apparatus to the extracellular space for filament assembly. Defects in the
FliS protein directly diminish bacterial motility, pathogenicity, and viability.
Although the overall structure of FliS is known, structural and mutational
studies on FliS from other bacterial species are still required to reveal any
unresolved biophysical features of FliS itself or functionally critical residues
for flagellin recognition. Here, we present the crystal structure of FliS from
Bacillus cereus (BcFliS) at 2.0 A resolution. FliS possesses a highly dynamic N
terminal region, which is appended to the common four-helix bundle structure. An
invariant proline residue (Pro17 in B. cereus FliS) was identified in all known
FliS sequences between the N-terminal region and the four-helix bundle. The N
terminal proline residue functions as a helix breaker critical for FliS
dimerization and flagellin recognition.
PMID- 28414128
TI - Impaired degradation of medullary WNK4 in the kidneys of KLHL2 knockout mice.
AB - Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and
Cullin3 (CUL3) genes were identified as being responsible for hereditary
hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the
KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of
interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired
ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC
cascade in the kidney's distal convoluted tubules (DCT). KLHL2, which is highly
homologous to KLHL3, was reported to ubiquitinate and degrade WNKs in vitro.
Mutations in KLHL2 have not been reported in patients with PHAII, suggesting that
KLHL2 plays a different physiological role than that played by KLHL3 in the
kidney. To investigate the physiological roles of KLHL2 in the kidney, we
generated KLHL2-/- mice. KLHL2-/- mice did not exhibit increased phosphorylation
of the OSR1/SPAK-NCC cascade and PHAII-like phenotype. KLHL2 was predominantly
expressed in the medulla compared with the cortex. Accordingly, medullary WNK4
protein levels were significantly increased in the kidneys of KLHL2-/- mice.
KLHL2 is indeed a physiological regulator of WNK4 in vivo; however, its function
might be different from that of KLHL3 because KLHL2 mainly localized in medulla.
PMID- 28414129
TI - The Arabidopsis endoplasmic reticulum associated degradation pathways are
involved in the regulation of heat stress response.
AB - The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein
Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum
are major pathways of the cellular proteostasis network. However, despite years
of effort, how these protein quality control systems coordinated in vivo remains
largely unknown, particularly in plants. In this study, the roles of two
evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response
were investigated through reverse genetic approaches in Arabidopsis. Phenotypic
analysis of the mutants showed that the two ERAD pathways additively play
negative roles in heat tolerance, which was demonstrated by higher survival rate
and lower electrolyte leakage in the loss of function mutants compared to the
wild type plants. Importantly, gene expression analysis revealed that the mutant
plants showed elevated transcriptional regulation of several downstream genes,
including those encoding CPR and UPR marker genes, under both basal and heat
stress conditions. Finally, multiple components of ERAD genes exhibited rapid
response to increasing temperature. Taken together, our data not only unravels
key insights into the crosstalk between different protein quality control
processes, but also provides candidate genes to genetically improve plant heat
tolerance in the future.
PMID- 28414130
TI - Effect of oxidation of the non-catalytic beta-propeller domain on the substrate
specificity of prolyl oligopeptidase from Pleurotus eryngii.
AB - Enzymes belonging to the S9 family of prolyl oligopeptidases are of interest
because of their pharmacological importance and have a non-catalytic beta
propeller domain. In this study, we found that the oxidation of Met203, which
lies on surface of the beta-propeller domain, leads to change in the substrate
specificity of eryngase, an enzyme from Pleurotus eryngii and a member of the S9
family of prolyl oligopeptidases. The activity of eryngase for L-Phe-p
nitroanilide was maintained following hydrogen peroxide treatment but was
dramatically reduced for other p-nitroanilide substrates. MALDI-TOF MS analysis
using tryptic peptides of eryngase indicated that the change in substrate
specificity was triggered by oxidizing Met203 to methionine sulfoxide. In
addition, mutations of Met203 to smaller residues provided specificities similar
to those observed following oxidation of the wild-type enzyme. Substitution of
Met203 with Phe significantly decreased activity, indicating that Met203 may be
involved in substrate gating.
PMID- 28414131
TI - Cyclical corticosterone administration sensitizes depression-like behavior in
rats.
AB - Because stress is a significant risk factor for depression, many animal models of
depression employ chronic stress as a precipitating event. However, almost
without exception, stress-induced animal models of depression focus on a single
bout of depression and therefore, they do not provide any means to understand the
typical cycling of mood observed in most patients with depression. Here we
assessed whether repeated cycles of exposure to the stress hormone corticosterone
would sensitize depression-like behavior. Rats were treated with corticosterone
(CORT; 20 or 40mg/kg) or vehicle for two cycles (21days each), followed by a 21
day recovery period. Depression-like behavior was assessed via repeated forced
swim tests (FSTs) in the middle and at the end of each CORT treatment and at the
end of each recovery period. Our results showed that CORT administration for two
cycles produces increasingly greater effects on depression-like behavior and a
decrease in recovery between cycles. Potential confounding effects of body weight
and repetitive behavioral testing are considered in the interpretation of these
effects. Our approach of using more than one cycle of CORT exposure provides
strong face validity as it mimics several aspects of human depression. The use of
multiple cycles of CORT exposure may provide a means to study the episode
recurrence seen in more than 70% of patients with depression.
PMID- 28414132
TI - Epigenetic modification of glucocorticoid receptor promoter I7 in maternally
separated and restraint-stressed rats.
AB - Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes
induced by environmental influences. Early life stress (ELS) has a persistent
impact on GR expression, as well as behavior, in adult rodents via epigenetic
changes of GR promoter I7. Moreover, various stressors can induce histone
modifications in this region during adulthood. Thus, the present study aimed to
investigate whether maternally separated (MS) rats exposed to chronic restraint
stress (RS) would exhibit histone modifications of GR promoter I7 in the
hippocampus. Rats were subjected to MS (3h per day) on postnatal days (PND) 1-21.
Then, during adulthood (PND 56-77), the rats were exposed to RS (2h per day)
followed by treatment with escitalopram (10mg/kg). The MS and RS groups exhibited
significant decreases in total and exon I7 GR mRNA levels and the combination of
MS and RS exerted a greater effect on these mRNA levels than either MS or RS
alone. Additionally, both the MS and RS groups showed significant reductions in
histone H3 acetylation at GR promoter I7 and the combination of MS and RS had a
greater effect than did either MS or RS alone. Chronic escitalopram treatment
ameliorated these changes. The present results indicate that postnatal MS and
adult RS influence GR expression through histone modification at GR promoter I7,
and that the combination of the two stressors potentiates these changes.
Furthermore, epigenetic mechanisms are involved in escitalopram action.
PMID- 28414133
TI - Complexity of weighted graph: A new technique to investigate structural
complexity of brain activities with applications to aging and autism.
AB - In recent years complexity of the brain structure in healthy and disordered
subjects has been studied increasingly. But to the best of the authors'
knowledge, researchers so far have investigated the structural complexity only in
the context of two restricted networks known as Small-World and Scale-free
networks; whereas other aspects of the structural complexity of brain activities
may be affected by aging and neurodegenerative disorders such as the Alzheimer's
disease and autism spectrum disorder. In this study, two general complexity
metrics of graphs, Graph Index Complexity and Offdiagonal Complexity are proposed
as general measures of complexity, not restricted to SWN only. They are adopted
to measure the structural complexity of the weighted graphs instead of the common
binary graphs. Fuzzy Synchronization Likelihood is applied to the EEGs and their
sub-bands, as a functional connectivity metric of the brain, to construct the
functional connectivity graphs. Two applications are used to evaluate the
efficacy of the complexity measures: diagnosis of autism and aging, both based on
EEG. It was discovered that the Graph Index Complexity of gamma band is
discriminative in distinguishing autistic children from non-autistic children.
Also, Offdiagonal Complexity of theta band in young subjects was observed to be
significantly different than old subjects. This study shows that changes in the
structure of functional connectivity of brain in disorders and different healthy
states can be revealed by unrestricted metrics of graph complexity. While the
applications presented in this paper are based on EEG, the approach is general
and can be used with other modalities such as fMRI, MEG, etc. Further, it can be
used to study every other neurological and psychiatric disorder.
PMID- 28414134
TI - Targeted intracorneal delivery-Biodistribution of triamcinolone acetonide
following topical iontophoresis of cationic amino acid ester prodrugs.
AB - The aim was to investigate intracorneal iontophoresis of biolabile triamcinolone
acetonide (TA) amino acid ester prodrugs (TA-AA). Arginine and lysine esters of
TA (TA-Arg and TA-Lys, respectively) were synthesized and characterized;
quantification was performed by HPLC-UV and UHPLC-MS/MS. The aqueous solubility
of the prodrugs (at pH 5.5) was ~1000-fold greater than TA. Anodal iontophoresis
(10min at 3mA/cm2) of TA-AA was investigated using isolated porcine cornea.
Although no statistically significant difference was observed in total
intracorneal delivery of TA (468.25+/-59.70 and 540.85+/-79.16nmolTA/cm2, for TA
Arg and TA-Lys, respectively), the different susceptibilities of the prodrugs to
hydrolysis influenced intracorneal biodistribution. Quantification of TA in
twenty-five 40MUm thick corneal lamellae revealed significantly deeper
penetration of TA following TA-Lys iontophoresis. Its superior resistance to
hydrolysis enabled sustained electromigration into the deeper cornea suggesting
judicious prodrug selection might enable targeted regioselective drug delivery.
The intracorneal biodistribution following anodal iontophoresis of TA-Arg (2.3mM;
10min, 3mA/cm2) was visualized by full field optical coherence tomography
providing qualitative confirmation of the extensive intracorneal penetration of
TA. Short duration iontophoresis of TA-AA prodrugs may improve deep corneal
bioavailability and efficacy in vivo, constituting a "single-shot" treatment
option for corneal allograft rejection.
PMID- 28414135
TI - Gastrointestinal behavior of itraconazole in humans - Part 1: Supersaturation
from a solid dispersion and a cyclodextrin-based solution.
AB - This study evaluated the fasted state gastrointestinal behavior of the lipophilic
drug itraconazole, orally administered to healthy volunteers as either a solid
dispersion (Sporanox(r) capsules) or a cyclodextrin-based solution (Sporanox(r)
solution). Following intake of the drug products, gastric and duodenal fluids
were aspirated and analyzed for itraconazole concentration, total content and
solubilizing capacity. Release of itraconazole from the solid dispersion
generated high and metastable supersaturated levels in the stomach, but the
dissolved fraction in the duodenum remained extremely low (median 2.5%). After
intake of the itraconazole solution, precipitation was limited in the stomach but
pronounced in the small intestine. Still, the dissolved fraction of itraconazole
in the duodenum (median 38%) appeared much higher than after intake of the solid
dispersion, possibly explaining the improved absorption of itraconazole from the
solution. As for the solid dispersion, the absorption-enabling ability of the
solution appeared mainly related to increased intraluminal concentrations by
means of supersaturation. Cyclodextrin-based solubilization of itraconazole
occurred only in the case of limited intraluminal dilution, but did not further
enhance itraconazole absorption. The obtained data will help to understand
critical aspects of supersaturating drug delivery systems and act as direct
reference for the optimization of in vitro simulation tools for gastrointestinal
drug behavior.
PMID- 28414136
TI - Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels:
The importance of pH and buffers on the microenvironment of vaginas.
AB - Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth.
Antibacterial agents are not optimal therapeutics of AV. Here, we report a series
of temperature-sensitive in situ forming acidic buffered gels for topical
treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and
6.5. AV rat models were prepared following vaginal infection with Staphylococcus
aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were
performed compared with ofloxacin gels and blank gels. All the buffered gels
showed the lower in vitro antibacterial activities than ofloxacin gels but the
better in vivo anti-S. aureus effects and similar anti-E. coli effects. The
buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat
vaginal pH and the pH of rat vaginas treated with the buffered gels were about
6.5 though the AV rat models or ones treated with ofloxacin gels still remained
at the high pH more than 7.0. After treatments with the buffered gels, the
vaginal smears changed to a clean state nearly without aerobic bacteria, the
vaginal tissues were refreshed, and the immunoreactions were downregulated. The
acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial
activities, improvement of probiotics, and alleviation of inflammation. They are
simple, highly efficient, and safe anti-AV formulations.
PMID- 28414137
TI - Novel dabigatran etexilate hemisuccinate-loaded polycap: Physicochemical
characterisation and in vivo evaluation in beagle dogs.
AB - The purpose of this study was to develop a novel dabigatran etexilate
hemisuccinate (DEH) salt-loaded polycap with bioequivalence to the dabigatran
etexilate mesylate (DEM)-loaded commercial product. DEH prepared with dabigatran
etexilate base (DE) and succinic acid was less hygroscopic but less soluble than
DEM. Numerous micronized DEHs and DEH-loaded solid dispersions were prepared
employing the spiral jet-milling and spray-drying techniques, respectively. Among
the formulations prepared, a micronized DEH prepared with the injection air at
1.5bar and the grinding air at 2bar, and a DEH-loaded solid dispersion prepared
with 6g HPMC most improved the drug solubility, respectively. Moreover, the
micronized DEH provided more increased drug solubility and dissolution compared
with the solid dispersion, even though its drug solubility was still lower than
that of DEM. Unlike the situation in other studies, the enhanced solubility and
dissolution of DEH was more due to particle size reduction than to a change to
the amorphous form. The micronized DEH prepared with Myrj 52S had greater drug
solubility than preparations with other surfactants. Among the organic acids
investigated, only fumaric acid (128.8mg) showed a similar pattern in pH changes
to the DEM-loaded commercial product. Furthermore, in order to make the
environment acidic while preventing the direct contact of the drug with fumaric
acid, the polycap was composed of a tablet containing the micronized DEH, Myrj
52S and other ingredients, and separate fumaric acid. This micronized DEH-loaded
polycap was dissolution- and bio-equivalent to the DEM-loaded commercial product
in beagle dogs. Thus, the novel micronized DEH-loaded polycap would be a
promising alternative to the DEM-loaded commercial product.
PMID- 28414138
TI - Apigenin, a modulator of PPARgamma, attenuates HFD-induced NAFLD by regulating
hepatocyte lipid metabolism and oxidative stress via Nrf2 activation.
AB - Lipid metabolic disorders and oxidative stress in the liver are key steps in the
progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk
factor for the development of metabolic syndrome. To date, no pharmacological
treatment for this condition has been approved. Our previous study has found that
the food-derived compound apigenin (Api) significantly attenuates obesity-induced
metabolic syndrome by acting as a peroxisome proliferator-activated receptor
gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was
used to dig out whether Api had the effect on NAFLD. The results showed that Api
had obvious effect in restraining NAFLD progression, including attenuating HFD
induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api
did significantly inhibit the expression of PPARgamma target genes encoding the
protein associated with lipid metabolism, it had no obvious activating effect on
PPARgamma. Interestingly, we found that Api promoted Nrf2 into the nucleus,
thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes
and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout
and overexpression experiments showed that Api regulating PPARgamma target genes
was dependent on Nrf2 activation and the activation of Nrf2 counteracted the
activation effect of PPARgamma by Api. Importantly, we also found that Api might
bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that
Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPARgamma in
inhibiting lipid metabolism and oxidative stress abnormity.
PMID- 28414139
TI - Ligand-dependent and -independent regulation of human hepatic sphingomyelin
phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk
with liver X receptor.
AB - Pregnane X receptor (PXR) mainly regulates xenobiotic metabolism and
detoxification. Additionally, it exerts pleiotropic effects on liver physiology,
which in large parts depend on transrepression of other liver-enriched
transcription factors. Based on the hypothesis that lower expression levels of
PXR may reduce the extent of this inhibition, an exploratory genome-wide
transcriptomic profiling was performed using HepG2 cell clones with different
expression levels of PXR. This screen and confirmatory real-time RT-PCR
identified sphingomyelin phosphodiesterase acid-like (SMPDL) 3A, a novel
nucleotide phosphodiesterase and phosphoramidase, as being up-regulated by PXR
deficiency. Transient siRNA-mediated knock-down of PXR in HepG2 cells and primary
human hepatocytes similarly induced mRNA up-regulation, which translated into
increased intracellular and secreted extracellular protein levels. Interestingly,
ligand-dependent PXR activation also induced SMPDL3A in HepG2 cells and primary
human hepatocytes. Electrophoretic mobility shift assays and chromatin
immunoprecipitation demonstrated binding of PXR to the previously identified
liver X receptor (LXR)-binding DR4 motif as well as to an adjacent ER8 motif in
intron 1 of SMPDL3A. Constitutive binding of the unliganded receptor to the
intron 1 chromatin indicated ligand-independent repression of SMPDL3A by PXR.
Transient transfection and reporter gene analysis confirmed the specific role of
these motifs in PXR- and LXR-dependent activation of the SMPDL3A intronic
enhancer. PXR inhibited LXR mainly by competition for binding sites. In
conclusion, this study describes that a decrease in PXR expression levels and
ligand-dependent activation of PXR and LXR increase hepatic SMPDL3A levels, which
possibly connects these receptors to hepatic purinergic signaling and
phospholipid metabolism and may result in drug-drug interactions with
phosphoramidate pro-drugs.
PMID- 28414140
TI - Shear stress inhibits IL-17A-mediated induction of osteoclastogenesis via
osteocyte pathways.
AB - Interleukin (IL)-17 is crucial to osteoclast differentiation and activation.
Osteocytes support osteoclast formation and are thought to orchestrate bone
remodeling in response to fluid flow. The contribution of IL-17 to osteocyte
related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4
cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It
was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation,
enhanced expression of receptor activator of nuclear factor kappa-B ligand
(RANKL) and tumor necrosis factor-alpha (TNF-alpha), and induced
osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived
macrophage (BMM) cells. Additionally, shear stress upregulated osteoprotegerin
expression in osteocytes, downregulated the effect of IL-17A on RANKL and TNF
alpha expression, and attenuated IL-17A-activated osteoclastic differentiation in
the co-culture system of MLO-Y4 and BMM cells. Furthermore, we explored the
signaling pathways that potentially mediate these effects in osteocytes, and
found that the extracellular signal-regulated kinase (ERK)1/2 and signal
transducer and activator of transcription (STAT3) pathways were suppressed by IL
17A but induced by fluid flow. EphA2 signaling enhances osteoclastogenesis in
osteocytes, and the intercellular reversed EphA2-ephrinA2 signaling from
osteocytes to BMM play an important role in IL-17A-dependent osteoclastic
differentiation. EphB4 signaling inhibits osteoclastogenesis in osteocytes, and
the intercellular reversed EphB4-ephrinB2 signaling from osteocytes to BMM could
inhibit IL-17A-dependent osteoclastic differentiation. The current findings
suggest that IL-17A as a promoter of bone resorption and fluid shear stress
critically regulate bone remodeling via osteocyte-specific signaling pathways. IL
17 modulation-based approaches may be developed as a novel therapeutic strategy
for enhancing bone remodeling efficiency and stability.
PMID- 28414141
TI - Temporal role of macrophages in cancellous bone healing.
AB - Macrophages are important phagocytosing and cytokine producing cells with effects
on fracture healing. We used clodronate-containing liposomes to reduce the number
of macrophages, in order to study their role in the early phases of cancellous
bone healing. Holes were drilled bilaterally into the cancellous bone of the
proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in
the right tibia. The day of surgery was day 0. Clodronate-containing liposomes
were injected intraperitoneally as a single injection either day -4 or -1 (before
surgery) or day 1 or 3 (after surgery). A control group underwent surgery as
above, but received no clodronate. The mice were killed day 7. The mechanical
quality of the new formed cancellous bone holding the screw was evaluated by a
pull-out test. The contents of the drill hole in the left tibia was analyzed by
microCT. Another set of 20 mice received a drill hole in the metaphysis of the
right tibia, and were given either clodronate or saline injections days -3 and
2. The animals were killed day 1 and 3. Flow cytometry was used to analyze the
composition of macrophage subpopulations in the regenerating tissue. Flow
cytometry showed that clodronate injections day -3 and -2 led to a decrease in
mature monocytes day 1 together with an increase in immature monocytes. On day 3
this effect had mostly disappeared, suggesting that the effect of the injections
lasted 3 to 5days. Mechanical testing revealed that the injections prior to
surgery decreased the strength of the new formed bone, holding the screw, by
about half. Bone density in the drill hole was similarly reduced. In contrast,
the injections given day 1 and 3 had smaller and statistically insignificant
effects. Since their depletion at later time points failed to produce a
significant effect, it seems that the role of macrophages in cancellous bone is
most crucial during the first two days after trauma.
PMID- 28414142
TI - Doxofylline does not increase formoterol-induced cAMP nor MKP-1 expression in ASM
cells resulting in lack of anti-inflammatory effect.
AB - The xanthine doxofylline has been examined in clinical trials and shown to have
efficacy and greater tolerability than theophylline in asthma and chronic
obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated
bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental
models of respiratory disease. However, there are limited studies in vitro. We
address this herein and examine whether doxofylline has anti-inflammatory impact
on primary cultures of airway smooth muscle (ASM) cells. We conduct a series of
investigations comparing and contrasting doxofylline with the archetypal
xanthine, theophylline, and the specific phosphodiesterase (PDE) 4 inhibitor,
cilomilast. We confirm that the xanthine drugs do not have action as PDE
inhibitors in ASM cells. Unlike cilomilast, doxofylline (and theophylline) do not
increase cAMP production in ASM cells induced by long-acting beta2-agonist
formoterol. Similar to theophylline, and consistent with the lack of cAMP
potentiation, doxofylline does not augment formoterol-induced upregulation of the
anti-inflammatory protein mitogen-activated protein kinase phosphatase 1 (MKP-1).
However, when we examine the effect of doxofylline on secretion of the
interleukin 8 from ASM cells stimulated by tumour necrosis factor (an in vitro
surrogate measure of inflammation), there was no repression of inflammation. This
is in contrast to the anti-inflammatory impact exerted by theophylline and
cilomilast in confirmatory experiments. In summary, our study is the first to
examine the effect of doxofylline on ASM cells in vitro and highlights some
distinct differences between two key members of xanthine drug family, doxofylline
and theophylline.
PMID- 28414143
TI - The Use of Hemoglobin Vesicles for Delivering Medicinal Gas for the Treatment of
Intractable Disorders.
AB - Bioactive gaseous molecules, such as oxygen (O2) and carbon monoxide (CO), are
essential elements for most living organisms to maintain their homeostasis and
biological activities. An accumulating body of evidence suggests that such
molecules can be used in clinics as a medical gas in the treatment of various
intractable disorders. Recent developments in hemoglobin-encapsulated liposomes,
namely hemoglobin vesicles (HbV), possess great potential for retaining O2 and CO
and could lead to strategies for the development of novel pharmacological agents
as medical gas donors. HbV with either O2 or CO bound to it has been demonstrated
to have therapeutic potential for treating certain intractable disorders and has
the possibility to serve as diagnostic and augmenting product by virtue of unique
physicochemical characteristics of HbV. The present review provides an overview
of the present status of the use of O2- or CO-binding HbV in experimental animal
models of intractable disorders and discusses prospective clinical applications
of HbV as a medical gas donor.
PMID- 28414144
TI - Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of
Preclinical and Clinical Findings.
AB - In recent years, an increasing number of clinical drug-drug interactions (DDIs)
have been attributed to inhibition of intestinal organic anion-transporting
polypeptides (OATPs); however, only a few of these DDI results were reflected in
drug labels. This review aims to provide a thorough analysis of intestinal OATP
mediated pharmacokinetic-based DDIs, using both in vitro and clinical
investigations, highlighting the main mechanistic findings and discussing their
clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a
total of 12 drugs were identified as possible clinical substrates of OATP2B1 and
OATP1A2. Among them, 3 drugs, namely atenolol, celiprolol, and fexofenadine, have
emerged as the most sensitive substrates to evaluate clinical OATP-mediated
intestinal DDIs when interactions with P-glycoprotein by the test compound can be
ruled out. With regard to perpetrators, 8 dietary or natural products and 1
investigational drug, ronacaleret (now terminated), showed clinical intestinal
inhibition attributable to OATPs, producing >=20% decreases in area under the
plasma concentration-time curve of the co-administered drug. Common juices, such
as apple juice, grapefruit juice, and orange juice, are considered potent
inhibitors of intestinal OATP2B1 and OATP1A2 (decreasing exposure of the co
administered substrate by ~85%) and may be adequate prototype inhibitors to
investigate intestinal DDIs mediated by OATPs.
PMID- 28414146
TI - Tissue Distribution of a Therapeutic Monoclonal Antibody Determined by Large Pore
Microdialysis.
AB - Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the
target tissues. Determination of target tissue interstitial concentration of mAbs
is an important aspect in the assessment of their
pharmacokinetic/pharmacodynamics relationship especially for mAbs targeting
membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG)
targeting human insulin-like growth factor-1 receptor was evaluated following a
single intravenous dose at 1, 6.25, and 25 mg/kg in healthy female SCID-beige
mice. R7072 showed linear pharmacokinetics over the dose range tested and was
characterized by low systemic clearance and long terminal half-life. Furthermore,
interstitial distribution of R7072 was evaluated in liver, skin, kidney, and
muscle tissues using large pore microdialysis (MD) after intravenous
administration of 10 mg/kg dose in mice. The relative recoveries of R7072 were
consistent and similar between in vitro and in vivo MD experiments. The tissue
and interstitial concentrations were significantly lower compared to serum
concentrations and found to be highest in liver and lowest in muscle. The
interstitial concentrations of R7072 were approximately 2-fold to 4-fold lower
than corresponding total tissue concentrations. Large pore MD appears to be an
attractive approach for direct measurement of pharmacologically relevant
concentrations of therapeutic mAbs in tissue interstitial fluid.
PMID- 28414147
TI - Public access to clinical trials: Lessons from an organizational implementation
of policy.
AB - Efforts to make clinical trials and their results more publicly available have
been increasing in recent years. However, there is a need to better understand
ways to achieve these goals aimed at benefiting a diverse set of stakeholders.
Since 2005, the U.S. Department of Veterans Affairs Office of Research and
Development (ORD), part of the nation's largest integrated health care system,
has required the clinical trials its funds to be registered in ClinicalTrials.gov
as a condition of the award. Furthermore, summary results of studies active since
2007 have been included in the registry. This paper highlights ORD activities,
challenges and lessons at investigator, study, and organizational levels. Key
factors in ORD's approach include: a mission-oriented approach; leadership
support; a working group for organizational policies and practices; prioritizing
communication; and recognizing the needs of investigators. Making clinical trials
available to the public should represent a focal point for groups desiring to
maximize the contributions from such research. The ability to do so must involve
a commitment by sponsors and a critical evaluation of the reasons, requirements
and resources at multiple levels.
PMID- 28414145
TI - Real-Time Analysis of Tenofovir Release Kinetics Using Quantitative Phosphorus
(31P) Nuclear Magnetic Resonance Spectroscopy.
AB - The dialysis method is classically used for drug separation before analysis, but
does not provide direct and real-time drug quantification and has limitations
affecting the dialysis rate. In this study, a phosphorus nuclear magnetic
resonance (31P-qNMR) method is developed for the real-time quantification of
therapeutic molecules in vitro. The release kinetics of model drug, tenofovir
(anti-HIV microbicide), was analyzed in vaginal fluid simulant (VFS), seminal
fluid simulant (SFS), and human plasma (HP) from chitosan nanofibers (size ~100
200 nm) using the NMR (direct) method and compared with dialysis/UV-Vis
(indirect) method. The assay was linear in VFS/SFS (0.20-5.0 mM), HP (0.30-5.0 mM
of drug concentration range) and specific no drug 31P-qNMR chemical shift [~15
ppm] interference with formulation/media components. Limit of detection values
were 0.075/0.10/0.20 mM, whereas limit of quantification values were
0.20/0.20/0.30 mM in VFS/SFS/HP, respectively. The method was robust, precise
(%RSE <2%), and accurate (%mean recovery 90%-110%). After 12 h, ~77%/72%/70%
wt/wt of tenofovir release was observed with direct, compared to ~47%/52%/52%
wt/wt by indirect method in VFS/SFS/HP, respectively. Approximately 20% decrease
in %drug release observed with dialysis method suggested an interference with
drug transport process due to the dialysis membrane and the Gibbs-Donnan effect.
Overall, 31P-qNMR provides more accurate, real-time, and direct drug
quantification for effective in vitro-in vivo correlation.
PMID- 28414148
TI - A close collaboration of chitosan with lipid colloidal carriers for drug delivery
applications.
AB - Chitosan and lipid colloids have separately shown a growing interest in the field
of drug delivery applications. Their success is mainly due to their interesting
physicochemical behaviors, as well as their biological properties such as
bioactivity and biocompatibility. While chitosan is a well-known cationic
polysaccharide with the ability to strongly interact with drugs and biological
matrices through mainly electrostatic interactions, lipid colloids are carriers
particularly recognized for the drug vectorization. In recent years, the
combination of both entities has been considered because it offers new systems
which gather the advantages of each of them to efficiently deliver various types
of bioactive species. The purpose of this review is to describe these
associations between chemically-unmodified chitosan chains (solubilized or
dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as
well as their potential in the drug delivery area so far. Three assemblies have
mainly been reported in the literature: i) lipid nanoparticles (solid lipid
nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii)
lipid vesicles covered with chitosan chains, and iii) chitosan chains structured
in nanoparticles with a lipid coating. Their elaboration processes, their
physicochemical characterization, and their biological studies are detailed and
discussed herein. The different bioactive species (drugs and bio(macro)molecules)
incorporated in these assemblies, their maximal incorporation efficiency, and
their loading capacity are also presented. This review reveals the versatility of
these assemblies. Depending on the organization of lipids (i.e., nanoparticles or
vesicles) and the state of polymer chains (i.e., solubilized or dispersed under
the form of nanoparticles), a large variety of drugs can be successfully
incorporated, and various routes of administration can be considered.
PMID- 28414149
TI - Nanosystem trends in drug delivery using quality-by-design concept.
AB - Quality by design (QbD) has become an inevitable trend because of its benefits
for product quality and process understanding. Trials have been conducted using
QbD in nanosystems' optimization. This paper reviews the application of QbD for
processing nanosystems and summarizes the application procedure. It provides
prospective guidelines for future investigations that apply QbD to nanosystem
manufacturing processes. Employing the QbD concept in this way is a novel area in
nanosystem quality.
PMID- 28414150
TI - Supramolecular nanoparticles of calcitonin and dipeptide for long-term controlled
release.
AB - Salmon calcitonin (sCT) is a therapeutic polypeptide drug widely used to treat
bone diseases such as osteoporosis (more than 200 million patients all over the
world). The half-life of sCT is very short (~1h), thus various delivery systems
have been developed for sCT in order to avoid frequent injections. However, most
delivery systems use polymeric materials, which may limit their applications in
clinic formulations due to the biocompatibility issue. We observed that a very
simple dipeptide (Asp-Phe, DF) was co-assembled with sCT into supramolecular
nanoparticles. These nanoparticles can significantly prolong the acting time of
sCT to beyond one month after just a single subcutaneous injection. The
assembling and releasing mechanisms were thoroughly investigated by both in vitro
and in vivo methods, as well as by molecular dynamics simulations. This work
provides an alternative strategy of designing protein/peptide drug delivery
systems with long-lasting therapeutic effects.
PMID- 28414151
TI - Targeted antigen delivery to dendritic cell via functionalized alginate
nanoparticles for cancer immunotherapy.
AB - The purpose of the present study was to identify an "easy-to-adopt" strategy to
enhance immune responses using functionalized alginate (ALG) nanoparticles (MAN
ALG/ALG=OVA NPs), which were prepared by CaCl2 cross-linking of two different
types of ALG. The mannose (MAN) modified ALG (MAN-ALG) was used for dendritic
cell targeting. The other component, composed of ovalbumin (OVA), a model
antigen, is conjugated to ALG (ALG=OVA) via pH sensitive Schiff base bond.
Grafting of alginate was demonstrated by FT-IR and 1H NMR, while the
morphological structure, particle size, Zeta potential of MAN-ALG/ALG=OVA NPs
were measured using TEM and DLS. The OVA releasing behavior of MAN-ALG/ALG=OVA
NPs was determined as a function of pH. Antigen uptake was examined by flow
cytometry and confocal laser scanning microscopy in vitro using mouse bone marrow
dendritic cells (BMDCs). The results showed that MAN-ALG/ALG=OVA NPs facilitated
antigen uptake of BMDCs and cytosolic release of the antigen. Significant up
regulation of cytokine secretion and expression levels of the surface co
stimulatory molecules were also observed in MAN-ALG/ALG=OVA NPs-treated BMDCs,
compared to free OVA. In vivo bio-distribution study using Cy7 (a near-infrared
fluorescence dye) labeled MAN-ALG/ALG=OVA NPs showed efficient in vivo
trafficking of the nanoparticles from the injection site to the draining lymph
nodes. Moreover, MAN-ALG/ALG=OVA NPs were found to enhance cross-presentation of
OVA to B3Z T cell hybridoma in vitro. Subcutaneous administration of MAN
ALG/ALG=OVA NPs also induced major cytotoxic T lymphocytes (CTL) response and
inhibition of E.G7 tumor growth in C57BL/6 mice. In summary, we report here that
the MAN-ALG/ALG=OVA NPs have the potential as a potent nanovaccine for cancer
immunotherapy.
PMID- 28414152
TI - Rituximab for immunologic renal disease: What the nephrologist needs to know.
AB - Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used
in immune-mediated renal diseases. While licensed in the induction treatment of
ANCA-associated vasculitis, it represents one of the most commonly prescribed off
label drugs. Much of the information regarding its safety has been drawn from
experience in hematology and rheumatology. Ample evidence illustrates the safety
of RTX, however, rare but serious adverse events have emerged that include
progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate
to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy
confer an increased infectious risk and factors predicting these side effects
(i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need
to bear in mind that long-term risks and optimal dosing for many renal
indications remain unclear. Special considerations must be given when RTX is used
in women of childbearing age. We summarize practical aspects concerning the use
of RTX. This review will provide nephrologists with information to guide their
use of RTX alerting them to safety risks and the need for patient counselling.
PMID- 28414153
TI - Inflammatory myopathy associated with myasthenia gravis with and without thymic
pathology: Report of four cases and literature review.
AB - INTRODUCTION: The association of myasthenia gravis (MG) and inflammatory myopathy
is rare and often only one of the diseases is diagnosed. Thymus pathology may be
in the origin of such disease association. METHODS: We described four patients
with both MG and inflammatory myopathy. RESULTS: These cases correspond to 2.3%
of our MG cohort. Case 1: MG, polymyositis and thymolipoma; case 2: MG and
necrotizing myopathy without thymic pathology on a background of scleroderma,
Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
(CREST); case 3: MG and dermatomyositis without thymic pathology; case 4: MG and
dermatomyositis with type C thymoma. DISCUSSION: The recognition of these
neuromuscular co-morbidities contributes to (i) understanding their pathogenic
mechanisms, (ii) developing better management approaches and (iii) further
improving disease outcomes.
PMID- 28414154
TI - Targeting synovial neoangiogenesis in rheumatoid arthritis.
AB - In Rheumatoid arthritis (RA), neoangiogenesis is an early and crucial event to
promote the development of the hyperplasic proliferative pathologic synovium.
Endothelial cells are critical for the formation of new blood vessels since they
highly contribute to angiogenesis and vasculogenesis. Current therapies in RA
target the inflammatory consequences of autoimmune activation and despite major
improvements these last years still refractory patients or incomplete responders
may be seen raising the point of the need to identify complementary additive and
innovative therapies. This review resumes the mechanisms of synovial
neoangiogenesis in RA, including recent insights on the implication of
vasculogenesis, and the regulation of synovial neoangiogenesis by angiogenic and
inflammatory mediators. In line with the recent development of vascular-targeted
therapies used in cancer and beyond, we also discuss possible therapeutic
implications in RA, in particular the combination of targeted immunotherapies
with anti-angiogenic molecules.
PMID- 28414155
TI - Recent advances in cochlear hair cell regeneration-A promising opportunity for
the treatment of age-related hearing loss.
AB - The objective of this paper is to review current information regarding the
treatment of age-related hearing loss by using cochlear hair cell regeneration.
Recent advances in the regeneration of the inner ear, including the usefulness of
stem cells, are also presented. Based on the current literature, cochlear cell
regeneration may well be possible in the short term and cochlear gene therapy may
also be useful for the treatment of hearing loss associated with ageing. The
present review provide further insight into the pathogenesis of Inner Ear
senescence and aged-related hearing loss and facilitate the development of
therapeutic strategies to repair hair cells damaged by ageing. More research will
be needed in order to translate them into an effective treatment for deafness
linked to cochlear senescence in humans.
PMID- 28414156
TI - Modeling of interactions between functional domains of ALDH1L1.
AB - ALDH1L1, a member of the aldehyde dehydrogenase superfamily of enzymes, catalyzes
the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2. The
enzyme is a tetramer of identical subunits, with each subunit consisting of three
functional domains that originated from unrelated genes. The N- and C-terminal
domains are catalytic, while the intermediate domain transfers the reaction
intermediate from the N- to the C-terminal domain. The intermediate domain is an
acyl carrier protein, possessing the covalently attached 4'-phosphopantetheine (4
PP) prosthetic group. This prosthetic group is known to function as a swinging
arm transferring intermediates between enzymes in complex biosynthetic reactions.
Here we have applied computer modeling using available structures of the three
functional domains of ALDH1L1 to evaluate the extent of flexibility within the
full-length protein. This approach allowed us to define positions of the 4-PP arm
within the two catalytic domains and to predict N-terminal:intermediate and
intermediate:C-terminal domain interfaces. Our models further suggested high
degree of flexibility within the full-length enzyme.
PMID- 28414157
TI - Commiphora molmol resin attenuates diethylnitrosamine/phenobarbital-induced
hepatocarcinogenesis by modulating oxidative stress, inflammation, angiogenesis
and Nrf2/ARE/HO-1 signaling.
AB - The objective of the current study was to investigate the possible
chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat
model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage
hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on
oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid
derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using
DEN for initiation and PB as a promoting agent. The rats received 125 or 250
mg/kg C. molmol resin extract throughout the experiment. Both doses of myrrh
improved liver function marker enzymes and prevented oval cells proliferation and
the distortion of hepatic architecture. The pro-inflammatory cytokine interleukin
6, tumor markers, angiogenesis markers, lipid peroxidation and nitric oxide (NO)
were significantly increased in DEN/PB-induced rats. In addition, the antioxidant
defenses showed marked reduction in the liver of DEN/PB-induced rats. Oral
administration of C. molmol extract to DEN/PB-induced rats significantly
decreased circulating markers of inflammation, tumor proliferation and
angiogenesis, and liver lipid peroxidation and NO. In addition, C. molmol
markedly ameliorated the antioxidant defenses and up-regulated Nrf2 and
hemeoxygenase (HO)-1 in the liver of DEN/PB-induced rats. In conclusion, these
results provide evidence that C. molmol resin has a potent chemopreventive
activity, possibly by up-regulating the Nrf2/HO-1 signaling and attenuation of
inflammation, angiogenesis and oxidative stress.
PMID- 28414158
TI - Methotrexate hepatotoxicity is associated with oxidative stress, and down
regulation of PPARgamma and Nrf2: Protective effect of 18beta-Glycyrrhetinic
acid.
AB - 18beta-glycyrrhetinic acid (18beta-GA) is a bioactive component of licorice with
promising hepatoprotective activity. However, its protective mechanism on
methotrexate (MTX) hepatotoxicity in not well defined. We investigated the
hepatoprotective effect of 18beta-GA, pointing to the role of peroxisome
proliferator activated receptor gamma (PPARgamma) and the redox-sensitive nuclear
factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered
18beta-GA (50 and 100 mg/kg) 7 days either before or after MTX injection. MTX
induced significant increase in circulating liver function marker enzymes and
bilirubin with concomitant declined albumin levels. Serum pro-inflammatory
cytokines, and liver malondialdehyde and nitric oxide were significantly
increased in MTX-induced rats. Treatment with 18beta-GA significantly reduced
serum enzymes of liver function, bilirubin and pro-inflammatory cytokines. 18beta
GA attenuated MTX-induced oxidative stress and restored the antioxidant defenses.
In addition, 18beta-GA improved liver histological structure and decreased the
expression of Bax whereas increased Bcl-2 expression. MTX-induced rats showed
significant down-regulation of Nrf2, hemoxygenase-1 and PPARgamma, an effect that
was markedly reversed by 18beta-GA supplemented either before or after MTX. In
conclusion, 18beta-GA protected against MTX-induced liver injury, possibly by
activating Nrf2 and PPARgamma, and subsequent attenuation of inflammation,
oxidative stress and apoptosis. Therefore, 18beta-GA can provide protection
against MTX-induced hepatotoxicity.
PMID- 28414159
TI - In vitro toxicological effects of zinc containing nanoparticles with different
physico-chemical properties.
AB - Nanomaterials (NM) exhibit novel physicochemical properties that determine their
interaction with biological substrates and processes. Recent nano-technological
advances are leading to wide usage of metallic nanoparticles (NPs) in various
fields. However, the increasing use of NPs has led to their release into
environment and the toxicity of NPs on human health has become a concern.
Moreover, there are inadvertently generated metallic NPs which are formed during
various human activities (e.g. metal processing and energy production).
Unfortunately, there are still widespread controversies and ambiguities with
respect to the toxic effects and mechanisms of metallic NPs, e.g. metal oxides
including ZnO. In this study, we generated zinc containing NMs, and studied them
in vitro. Different nano-sized particles containing Zn were compared in in vitro
study to elucidate the physicochemical characteristics (e.g. chemical
composition, solubility, shape and size of the particles) that determine cellular
toxicity. Zn induced toxicity in macrophage cell line (RAW 264.7) was detected,
leading to the cell cycle disruption, cell death and excitation of release of
inflammatory mediators. The solubility and the size of Zn compounds had a major
role in the induced toxic responses. The soluble particles reduced the cell
viability, whereas the less soluble NPs significantly increased inflammation.
Moreover, uptake of large ZnO NPs inside the cells was likely to play a key role
in the detected cell cycle arrest.
PMID- 28414160
TI - Paraquat induces extrinsic pathway of apoptosis in A549 cells by induction of DR5
and repression of anti-apoptotic proteins, DDX3 and GSK3 expression.
AB - Paraquat (PQ) is a bipyridyl derivative herbicide known to cause lung toxicity
partly through induction of apoptosis. Here we demonstrated that PQ caused
apoptosis in A549 cells. PQ increased cleavage of caspase-8 and Bid, indicating
caspase-8 activation and truncated Bid, the two key mediators of extrinsic
apoptosis. Additionally, PQ treatment caused an increase in DR5 (death receptor
5) and caspase-8 interaction, indicating formation of DISC (death-inducing
signaling complex). These results indicate that PQ induces apoptosis through
extrinsic pathway in A549 cells. Moreover, PQ drastically increased DR5
expression and membrane localization. Furthermore, PQ caused prominent
concentration dependent reductions of DDX3 (the DEAD box protein-3) and GSK3
(glycogen synthase kinase-3) which can associate with DR5 and prevent DISC
formation. Additionally, PQ decreased DR5-DDX3 interaction, suggesting a
reduction of DDX3/GSK3 anti-apoptotic complex. Inhibition of GSK3, which is known
to promote extrinsic apoptosis by its pharmacological inhibitor, BIO accentuated
PQ-induced apoptosis. Moreover, GSK3 inhibition caused a further decrease in PQ
reduced DR5-DDX3 interaction. Taken together, these results suggest that PQ may
induce extrinsic pathway of apoptosis in A549 cells through upregulation of DR5
and repression of anti-apoptotic proteins, DDX3/GSK3 leading to reduction of anti
apoptotic complex.
PMID- 28414161
TI - Metabolism of okadaic acid by NADPH-dependent enzymes present in human or rat
liver S9 fractions results in different toxic effects.
AB - The lipophilic marine biotoxin okadaic acid (OA) represents a natural contaminant
produced by algae accumulating in seafood. Acute intoxications result in
diarrhetic shellfish poisoning causing symptoms like nausea, vomiting and
abdominal cramps. OA was preincubated with liver enzymes present in S9 fractions
from humans, rats and rats pretreated with enzyme inducers in the presence or
absence of the cofactor NADPH to investigate hepatic metabolism. Cytotoxicity was
examined in HepG2 cells and metabolites of OA were determined by LC-MS/MS. Strong
cytotoxicity was observed in HepG2 cells treated with OA that was preincubated in
S9 fractions without NADPH. However, neither metabolites nor a decrease of OA
itself were found. The addition of NADPH to the S9 fractions of rats resulted in
a decreased cytotoxicity of OA, but a stronger toxicity in HepG2 cells was
observed from OA preincubated in human S9 fractions with NADPH. Metabolite
profiles of each S9 mix revealed that higher amounts of detoxified metabolites
were formed by NADPH-dependent enzymes of rats compared to the same enzymes of
humans. These differences in OA detoxification by NADPH-dependent liver enzymes
of rats and humans may be of significance in the extrapolation of toxicological
data from animal models (rats to humans, for example).
PMID- 28414162
TI - Biological response of HeLa cells to gold nanoparticles coated with organic
molecules.
AB - In this work, gold nanospheres functionalized with low weight organic molecules
(4-aminothiphenol and cysteamine) were synthesized in a one-step method for their
in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of
the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high
binding affinity to gold nanoparticles. Besides, the widely reported silica
coated gold nanorods were tested here to contrast their toxic response against
our nanoparticles coated with organic molecules. Our results shown, the viability
measured at 1.9*10-5M did not show significant differences against negative
controls for all the samples; however, the metabolic activity of HeLa cells
dropped when they were exposed to silica gold nanorods in the range of
concentrations from 2.9*10-7M to 3.0*10-4M, while in the cases of gold
nanospheres, we found that only at concentrations below 1.9*10-5M metabolic
activity was normal. Our preliminary results did not indicate any perceivable
harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres
at 1.9*10-5M. Additional test should be conducted in order to ensure a safe use
of them for biological applications, and to determine the extent of possible
damage.
PMID- 28414163
TI - Droplet digital PCR (ddPCR) vs quantitative real-time PCR (qPCR) approach for
detection and quantification of Merkel cell polyomavirus (MCPyV) DNA in formalin
fixed paraffin embedded (FFPE) cutaneous biopsies.
AB - BACKGROUND: Merkel cell polyomavirus (MCPyV) is associated with Merkel cell
carcinoma and high viral load in the skin was proposed as a risk factor for the
occurrence of this tumour. MCPyV DNA was detected, with lower frequency, in
different skin cancers but since the viral load was usually low, the real
prevalence of viral DNA could be underestimated. OBJECTIVE: To evaluate the
performance of two assays (qPCR and ddPCR) for MCPyV detection and quantification
in formalin fixed paraffin embedded (FFPE) tissue samples. METHODS: Both assays
were designed to simultaneous detection and quantification of both MCPyV as well
as house-keeping DNA in clinical samples. The performance of MCPyV quantification
was investigated using serial dilutions of cloned target DNA. We also evaluated
the applicability of both tests for the analysis of 76 FFPE cutaneous biopsies.
RESULTS: The two approaches resulted equivalent with regard to the
reproducibility and repeatability and showed a high degree of linearity in the
dynamic range tested in the present study. Moreover, qPCR was able to quantify
>=105 copies per reaction, while the upper limit of ddPCR was 104 copies. There
was not significant difference between viral load measured by the two methods The
detection limit of both tests was 0,15 copies per reaction, however, the number
of positive samples obtained by ddPCR was higher than that obtained by qPCR (45%
and 37% respectively). CONCLUSIONS: The ddPCR represents a better method for
detection of MCPyV in FFPE biopsies, mostly these containing low copies number of
viral genome.
PMID- 28414164
TI - A Pre-Hospital Extracorporeal Cardio Pulmonary Resuscitation (ECPR) strategy for
treatment of refractory out hospital cardiac arrest: An observational study and
propensity analysis.
AB - BACKGROUND: Out of hospital cardiac arrest (OHCA) mortality rates remain very
high with poor neurological outcome in survivors. Extracorporeal cardiopulmonary
resuscitation (ECPR) is one of the treatments of refractory OHCA. This study used
data from the mobile intensive care unit (MOICU) as part of the emergency medical
system of Paris, and included all consecutive patients treated with ECPR
(including pre-hospital ECPR) from 2011 to 2015 for the treatment of refractory
OHCA, comparing two historical ECPR management strategies. METHODS: We
consecutively included refractory OHCA patients. In Period 1, ECPR was indicated
in selected patients after 30min of advanced life support; in- or pre-hospital
implementation depended on estimated transportation time and ECPR team
availability. In Period 2, patient care relied on early ECPR initiation after
20min of resuscitation, stringent patient selection, epinephrine dose limitation
and deployment of ECPR team with initial response team. Primary outcome was
survival with good neurological function Cerebral Performance Category score (CPC
score) 1 and 2 at ICU discharge or day 28. FINDINGS: A total of 156 patients were
included. (114 in Period 1 and 42 in Period 2). Baseline characteristics were
similar. Mean low-flow duration was shorter by 20min (p<0.001) in Period 2.
Survival was significantly higher in Period 2: 29% vs 8% (P<0.001), as confirmed
by the multivariate analysis and propensity score. When combining stringent
patient selection with an aggressive strategy, the survival rate increased to
38%. Pre-hospital ECPR implementation in itself was not an independent predictor
of improved survival, but it was part of the strategy in Period 2.
INTERPRETATION: Our data suggest that ECPR in specific settings in the management
of refractory OHCA is feasible and can lead to a significant increase in
neurological intact survivors. These data, however, need to be confirmed by a
large RCT.
PMID- 28414165
TI - Recognising out-of-hospital cardiac arrest during emergency calls increases
bystander cardiopulmonary resuscitation and survival.
AB - BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR)
depends on bystanders' or medical dispatchers' recognition of out-of-hospital
cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA
recognition during the emergency call was associated with bystander CPR, return
of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to
identify patient-, setting-, and dispatcher-related predictors of OHCA
recognition. METHODS: We performed an observational study of all OHCA patients'
emergency calls in the Capital Region of Denmark from 01/01/2013-31/12/2013.
OHCAs were collected from the Danish Cardiac Arrest Registry and the Mobile
Critical Care Unit database. Emergency call recordings were identified and
evaluated. Multivariable logistic regression analyses were applied to all OHCAs
and witnessed OHCAs only to analyse the association between OHCA recognition and
bystander CPR, ROSC, and 30-day survival. Univariable logistic regression
analyses were applied to identify predictors of OHCA recognition. RESULTS: We
included 779 emergency calls in the analyses. During the emergency calls, 70.1%
(n=534) of OHCAs were recognised; OHCA recognition was positively associated with
bystander CPR (odds ratio [OR]=7.84, 95% confidence interval [CI]: 5.10-12.05) in
all OHCAs; and ROSC (OR=1.86, 95% CI: 1.13-3.06) and 30-day survival (OR=2.80,
95% CI: 1.58-4.96) in witnessed OHCA. Predictors of OHCA recognition were
addressing breathing (OR=1.76, 95% CI: 1.17-2.66) and callers located by the
patient's side (OR=2.16, 95% CI: 1.46-3.19). CONCLUSIONS: Recognition of OHCA
during emergency calls was positively associated with the provision of bystander
CPR, ROSC, and 30-day survival in witnessed OHCA.
PMID- 28414166
TI - Evaluation and application of molecular genotyping on nosocomial pathogen
methicillin-resistant Staphylococcus aureus isolates in Guangzhou representative
of Southern China.
AB - Staphylococcus aureus is recognized as a typical food-born pathogen in food
safety, and its rapid detection and typing methods are in desperate need. To
study their evolution characteristics and drug resistance condition,
Staphylococci isolates were subject to the investigation. Strain identification
were subjected to standard procedures (colony morphology, Gram staining, Vitek 2
automated system and the API commercial kit), and fingerprinting was then
performed with RAPD-PCR amplification. In this study, 179 isolated staphylococci
were identified as MRSA. In addition, Staphylococci isolates were subjected to
three different fingerprinting system (ERIC2, AP1 and AP7) and then genotyped
based on significant diversities. Nosocomial epidemiology was then conducted
according to the fingerprint result. To sum up, the RAPD method subjected for
MRSA rapid genotyping have a broad application prospect in food safety and
epidemiology.
PMID- 28414167
TI - Inhibition of the mitochondrial respiratory chain in gills of Rhamdia quelen
experimentally infected by Pseudomonas aeruginosa: Interplay with reactive oxygen
species.
AB - It has long been recognized that there are several infectious diseases linked to
the impairment of enzymatic complexes of the mitochondrial respiratory chain,
with consequent production of reactive oxygen species (ROS), that contribute to
disease pathogenesis. In this study, we determined whether the inhibition on
mitochondrial respiratory chain might be considered a pathway involved in the
production of ROS in gills of Rhamdia quelen experimentally infected by P.
aeruginosa. The animals were divided into two groups with six fish each:
uninfected (the negative control group) and infected (the positive control
group). On day 7 post-infection (PI), animals were euthanized and the gills were
collected to assess the activities of complexes I-III, II and IV of the
respiratory chain, as well as ROS levels. The activities of complexes I-III, II
and IV of the respiratory chain in gills decreased, while the ROS levels
increased in infected compared to uninfected animals. Moreover, a significant
negative correlation was found between enzymatic activity of the complexes I-III
and IV related to ROS levels in P. aeruginosa infected animals, corroborating to
our hypothesis that inhibition on complexes of respiratory chain leads to ROS
formation. Also, microscopic severe gill damage and destruction of primary and
secondary lamellae were observed in infected animals, with the presence of
hyperplasia, leukocytic infiltration and telangiectasia. In summary, we have
demonstrated, for the first time, that experimental infection by P. aeruginosa
inhibits the activities of mitochondrial complexes of respiratory chain and,
consequently, impairs the cellular energy homeostasis. Moreover, the inhibition
on mitochondrial complexes I-III and IV are linked to the ROS production,
contributing to disease pathogenesis.
PMID- 28414168
TI - Decompression alone versus fusion for pyogenic spondylodiscitis.
AB - BACKGROUND CONTEXT: A spinal infection is a serious problem for a spine surgeon,
and there is currently much debate regarding how best to treat pyogenic
spondylodiscitis using antibiotics and the instrumentations that have been
developed to date. PURPOSE: The purpose of this study was to determine which
method is better for treating pyogenic spondylodiscitis. STUDY DESIGN: A
retrospective chart review was performed. PATIENT SAMPLE: Thirty-one patients
with pyogenic spondylodiscitis underwent surgical treatment between 2000 and 2016
at the authors' institution. OUTCOME MEASURES: Clinical outcomes were assessed
using a visual analog scale (VAS). We measured translation and rotation on
flexion and extension X-rays to identify instability. METHODS: Patients were
divided into two groups: Group I, decompression group; Group II, decompression
plus fusion group. Group I exhibited no instability according to a preoperative
radiographic study, whereas Group II exhibited instability. Both groups were
compared with respect to demographics and laboratory findings, including tests to
determine C-reactive protein (CRP) levels and erythrocyte sedimentation rates
(ESR), organisms, and the total duration of antibiotic treatment after the
operation. We compared the results of the preoperative, postoperative, and last
follow-up radiographic examinations of the sagittal alignment of the infected
segment. This study was supported by a clinical research fund (4,500 dollars)
from the National Health Insurance Service, Ilsan Hospital. RESULTS: A total of
31 patients were included; 22 (71%) were in Group I and 9 (29%) were in Group II.
On radiological examination, the mean preoperative translation and rotation
values in Group I were 2.45+/-1.22 mm and 5.64+/-1.98 degrees , and in Group II
were 5.35+/-1.65 mm and 12.01+/-4.22 degrees . At the last follow-up, the mean
translation and rotation values in Group I were 1.95+/-1.75 mm and 2.69+/-1.61
degrees , and in Group II were 1.77+/-1.02 mm and 3.44+/-2.07 degrees . Both
Groups I and II exhibited stability after the operation. No differences were
detected in preoperative ESR and CRP levels between the two groups. Group I,
compared with Group II, experienced a shorter duration of treatment with
antibiotics and normalization of ESR and CRP levels after the operation and a
shorter hospitalization period. CONCLUSIONS: If the appropriate antibiotics are
administered quickly when there is no instability, decompression alone is
effective; however, if instability is detected, decompression plus fusion can be
used to achieve stability.
PMID- 28414169
TI - A biomechanical investigation of different screw head designs for vertebral
derotation in scoliosis surgery.
AB - BACKGROUND CONTEXT: The posterior pedicle screw-rod system, which is widely used
to correct spinal deformities, achieves a good correction rate in the frontal and
coronal planes but not in the axial plane. Direct vertebral derotation (DVD) was
developed to correct axial plane deformities. However, the design of screw head
and body connection, in terms of monoaxial, polyaxial, and uniplanar screw, may
influence the efficiency of DVD. PURPOSE: This study compared the efficiency of a
newly designed uniplanar screw with that of monoaxial and polyaxial screws in the
DVD maneuver. STUDY DESIGN: A porcine spine model and monoaxial, polyaxial, and
uniplanar screws were used to examine the biomechanics of the DVD maneuver.
METHODS: Six T7-T13 porcine thoracic spine segments were used as test specimens
in this study. Pedicle screws were inserted in the left pedicles of the T9-T11
spinal segments and then connected with a rod. Three types of pedicle screws with
different screw head designs (monoaxial, polyaxial, and uniplanar) were employed
in this study. The material testing system (MTS) machine generated a rotational
moment through the derotational tube on the T10 (apical body) pedicle screw,
which simulated the motion applied during the surgical vertebral derotational
procedure. The pedicle strain and the kinematics of the vertebral body and
derotational tube were recorded to evaluate the derotational efficiency of
different pedicle screw head designs. RESULTS: The variances of the derotation
for the monoaxial, polyaxial, and uniplanar screws were 2.22 degrees +/-1.43
degrees , 32.23 degrees +/-2.26 degrees , and 4.75 degrees +/-1.60 degrees ,
respectively; the derotation efficiency was 0.65, 0.51, and 0.12, respectively,
when the torques of the spinal constructs reached 3 Nm. The rotational variance
of the polyaxial screw was statistically greater than that of the monoaxial and
uniplanar screws (p<.05). The maximum micro-strains of the pedicles for the
monoaxial, polyaxial, and uniplanar screws were 1,067.45+/-550.35, 747.68+/
393.56, and 663.55+/-271.04, respectively, with no statistically significant
differences (p>.05). CONCLUSIONS: The screw head design played an important role
in the efficiency and variance of the derotation during the DVD maneuver. The
derotational efficiency of the newly designed uniplanar screw was closer to that
of the monoaxial screw group than to that of the polyaxial screw group. The
polyaxial screw was inferior to DVD owing to a derotational variance between the
derotational tube and the apical body that was correlated with the range of
motion of the screw head. In the present study, the pedicle strain was similar in
all groups. However, the pedicle strain of the uniplanar screw group was lower
than that of the monoaxial screw group and was similar to that of the polyaxial
screw group when the angle of rotation of the apical body increased.
PMID- 28414170
TI - Importance of patient-reported individualized goals when assessing outcomes for
adult spinal deformity (ASD): initial experience with a Patient Generated Index
(PGI).
AB - BACKGROUND CONTEXT: Current metrics to assess patients' health-related quality of
life (HRQOL) may not reflect a true change in the patients' specific perception
of what is most important to them. PURPOSE: This study aimed to describe the
initial experience of a Patient Generated Index (PGI) in which patients create
their own outcome domains. STUDY DESIGN: This is a single-center prospective
study. PATIENT SAMPLE: Patients with adult spinal deformity (ASD) comprise the
study sample. OUTCOME MEASURES: Oswestry Disability Index (ODI), Short Form-36
(SF-36 Physical Component Score [PCS] and Mental Component Score [MCS]),
Scoliosis Research Society-22r (SRS-22r), and PGI. METHODS: Oswestry Disability
Index, SF-36, SRS-22r, and PGI were administered preoperatively and
postoperatively at 6 weeks, 3 months, 6 months, and 1 and 2 years. PGI
correlations with ODI, SF-36, SRS total score, free-text frequency analysis of
PGI exact response with text in ODI and SRS-22r questionnaires, and the
responsiveness (effect size [ES]) of the HRQOL metrics were analyzed. No funding
was used for this study and there are no conflicts of interest. RESULTS: A total
of 59 patients with 209 clinical encounters produced 370 PGI written response
topics that included affect or emotions, relationships, activities of daily life,
personal care, work, and hobbies. Mean preoperative PGI score was 18.6+/-13.5 (0
71.7 out of 100 [best]), and mean scores significantly improved at every
postoperative time point (p<.05). Preoperative PGI scores significantly
correlated with preoperative ODI (r=-0.28, p=.03), MCS (r=0.48, p<.01), and SRS
total (r=0.57, p<.01). Postoperative PGI scores correlated with all HRQOL
measures (p<.0001): ODI (r=-0.65), PCS (r=0.50), MCS (r=0.55), and SRS total
(r=0.63). PGI responses exactly matched ODI and SRS-22r text at 47.8% and 35.4%,
respectively, and at 63.2% and 58.9%, respectively, for categories. Patient
Generated Index ES at a minimum of 1-year follow-up was -2.39, indicating
substantial responsiveness (|ES|>0.8). Effect sizes for ODI, SRS-22r total, SF-36
PCS, and SF-36 MCS were 2.16, -2.06, -2.05, and -0.80, respectively. CONCLUSIONS:
The PGI is easy to administer and offers additional information about the
patients' perspective not captured in standard HRQOL metrics. Patient Generated
Index scores correlated with all of the standard HRQOL scores and were more
responsive than ODI, SF-36, and SRS-22r, suggesting that the PGI may be a step
closer to one HRQOL measure that better encompasses concerns and goals of the
individual patients.
PMID- 28414171
TI - The effects of water on degradation of the zirconia-resin bond.
AB - OBJECTIVES: 10-methacryloyloxydecyldihydrogenphosphate (MDP) containing primers
improve bonding of yttria-stabilised tetragonal zirconia (Y-TZP) to methacrylate
resins. The present study investigated the role played by water in the
deterioration of MDP-mediated zirconia-resin bonds. METHODS: Grit-blasted Y-TZP
plates were conditioned with two MDP primers and bonded with resin for shear bond
strength (SBS) testing. Additional bonded plates were aged hydrothermally and
compared with unaged Y-TZP after 24h of water-storage or 6 months of
water/acid/alkali-storage. The monoclinic phase (m-ZrO2) in different groups was
determined by X-ray diffraction. Hydrolytic stability of the coordinate bond
between MDP and zirconia in neutral/acid/alkaline environment was analysed using
thermodynamic calculations. Microleakage and release of the element phosphorus
from MDP-mediated Y-TZP/resin-bonded interfaces were evaluated via methylene blue
dye infiltration and inductively coupled plasma-mass spectrometry (ICP-MS).
RESULTS: Hydrothermal ageing did not significantly alter SBS. Ageing in acidic or
neutral medium led to significant decline in SBS. The m-ZrO2 phase increased
after hydrothermal ageing but no m-ZrO2 was detected in the water/acid/alkali
aged specimens. A higher equilibrium constant was identified in the MDP-t-ZrO2
complex when compared with the MDP-m-ZrO2 complex. MDP-conditioning failed to
prevent infiltration of the methylene blue dye. Phosphorus was detected by ICP-MS
from the solutions used for soaking the resin-bonded specimens. CONCLUSIONS:
Hydrolysis of the coordinate bond between MDP and ZrO2, rather than t->m phase
transformation, weakens the bond integrity between MDP-conditioned Y-TZP and
methacrylate resin. CLINICAL SIGNIFICANCE: Hydrolysis of the coordinate bond
between MDP and zirconia is responsible for deterioration of the integrity of the
bond between MDP-conditioned Y-TZP and methacrylate resin.
PMID- 28414172
TI - LCCL protein complex formation in Plasmodium is critically dependent on LAP1.
AB - Successful sporogony of Plasmodium berghei in vector mosquitoes requires
expression of a family of six modular proteins named LCCL lectin domain adhesive
like proteins (LAPs). The LAPs share a subcellular localization in the
crystalloid, a unique parasite organelle that forms during ookinete development.
Here, LAP interactions in P. berghei were studied using a series of parasite
lines stably expressing reporter-tagged LAPs combined with affinity purification
and high accuracy label free quantitative mass spectrometry. Our results show
that abundant complexes containing LAP1, LAP2 and LAP3 are formed in gametocytes
through high avidity interactions. Following fertilization, LAP4, LAP5 and LAP6
are recruited to this complex, a process that is facilitated by LAP1 chiefly
through its scavenger receptor cysteine-rich modules. These collective findings
provide new insight into the temporal and molecular dynamics of protein complex
formation that lead up to, and are required for, crystalloid biogenesis and
downstream sporozoite transmission of malaria parasites.
PMID- 28414173
TI - Affinity interactions drive post-implantation drug filling, even in the presence
of bacterial biofilm.
AB - : Current post-operative standard of care for surgical procedures, including
device implantations, dictates prophylactic antimicrobial therapy, but a
percentage of patients still develop infections. Systemic antimicrobial therapy
needed to treat such infections can lead to downstream tissue toxicities and
generate drug-resistant bacteria. To overcome issues associated with systemic
drug administration, a polymer incorporating specific drug affinity has been
developed with the potential to be filled or refilled with antimicrobials, post
implantation, even in the presence of bacterial biofilm. This polymer can be used
as an implant coating or stand-alone drug delivery device, and can be translated
to a variety of applications, such as implanted or indwelling medical devices,
and/or surgical site infections. The filling of empty affinity-based drug
delivery polymer was analyzed in an in vitro filling/refilling model mimicking
post-implantation tissue conditions. Filling in the absence of bacteria was
compared to filling in the presence of bacterial biofilms of varying maturity to
demonstrate proof-of-concept necessary prior to in vivo experiments. Antibiotic
filling into biofilm-coated affinity polymers was comparable to drug filling seen
in same affinity polymers without biofilm demonstrating that affinity polymers
retain ability to fill with antibiotic even in the presence of biofilm.
Additionally, post-implantation filled antibiotics showed sustained bactericidal
activity in a zone of inhibition assay demonstrating post-implantation capacity
to deliver filled antibiotics in a timeframe necessary to eradicate bacteria in
biofilms. This work shows affinity polymers can fill high levels of antibiotics
post-implantation independent of biofilm presence potentially enabling device
rescue, rather than removal, in case of infection. STATEMENT OF SIGNIFICANCE:
Post-operative prophylactic antimicrobial therapy greatly reduces risk of
infection, such as on biomedical implants, but does not totally eliminate
infections, and the healthcare cost of these remaining infections remains a major
concern. Systemic antimicrobial therapy to treat these infections can lead to
tissue toxicity and drug-resistant bacteria. In order to treat only those
patients who have developed infections, a customizable antimicrobial delivery
system made of cyclodextrin-based affinity polymer has been developed that is
capable of filling post-implantation and delivering the filled antibiotic in a
sustained manner even when the delivery device covered in bacterial biofilm.
These observations have the potential to be translated to a wide variety of
applications, such as implanted or indwelling medical devices, and/or surgical
site infections.
PMID- 28414174
TI - Iterative integration of multiple-copy pathway genes in Yarrowia lipolytica for
heterologous beta-carotene production.
AB - beta-Carotene is a terpenoid molecule with high hydrophobicity that is often used
as an additive in foods and feed. Previous work has demonstrated the heterologous
biosynthesis of beta-carotene from an intrinsic high flux of acetyl-CoA in 12
steps through 11 genes in Yarrowia lipolytica. Here, an efficient biosynthetic
pathway capable of producing 100-fold more beta-carotene than the baseline
construct was generated using strong promoters and multiple gene copies for each
of the 12 steps. Using fed-batch fermentation with an optimized medium, the
engineered pathway could produce 4g/L beta-carotene, which was stored in lipid
droplets within engineered Y. lipolytica cells. Expansion of these cells for
squalene production also demonstrated that Y. lipolytica could be an industrially
relevant platform for hydrophobic terpenoid production.
PMID- 28414175
TI - Success in the acquisition of Bombyx mori sperm motility is influenced by the
extracellular production of nitric oxide (NO) in the presence of seminal fluid
nitric oxide synthase (NOS).
AB - A trypsin-like protease called initiatorin is known to initiate sperm motility in
the silkworm, Bombyx mori, but little is known about the signaling events leading
to sperm flagellar beating. The aim of this study was to investigate whether this
mechanism of sperm motility activation involves the signaling transmitter nitric
oxide (NO). NO is produced from the amino acid L-arginine by the enzyme action of
nitric oxide synthase (NOS; EC 1.14.13.39). Simple treatment of quiescent sperm
with an NO donor (SNAP or NOC7) in vitro did not lead to activation of motility.
Nevertheless, initiatorin- or trypsin-induced motility was blocked by
pretreatment of sperm with either the NOS inhibitor L-NAME or NO scavenger
carboxy-PTIO. These observations suggested that NO may play important
physiological roles in the acquisition of sperm motility under the in vitro
condition used here. Then, we investigated whether NO synthesis would occur in
the spermatophore, a capsule containing spermatozoa that is created by the
contents of various male reproductive glands and is the site of sperm maturation.
The amounts of NO2- and NO3-, stable metabolites of NO, reached maximum values
after enclosure in the spermatophore, a time when apyrene spermatozoa acquire
vigorous motility. Moreover, RT-PCR and Western blotting analyses of NOS
indicated that it is abundantly expressed in glandula (g.) lacteola of the virgin
male ejaculatory duct, from which it is secreted to the seminal fluid and
transferred to the female during mating. Previous studies demonstrated that free
L-arginine is supplied de novo by a specific proteolytic reaction in which
initiatorin participates during spermatophore formation (Osanai et al., 1987c).
Based on these results, it can be presumed that the mixing of seminal fluid
contents from each male reproductive organ during ejaculation induced NO
production outside of the spermatid, and exogenous NO stimulated a signaling
pathway involved in the activation of silkworm apyrene sperm.
PMID- 28414176
TI - Genome specific PPARalphaB duplicates in salmonids and insights into estrogenic
regulation in brown trout.
AB - Peroxisome proliferator-activated receptors (PPARs) are key regulators of many
processes in vertebrates, such as carbohydrate and lipid metabolism. PPARalpha, a
member of the PPAR nuclear receptor gene subfamily (NR1C1), is involved in fatty
acid metabolism, namely in peroxisomal beta-oxidation. Two gene paralogues,
pparalphaA and pparalphaB, were described in several teleost species with their
origin dating back to the teleost-specific genome duplication (3R). Given the
additional salmonid-specific genome duplication (4R), four genes could be
theoretically anticipated for this gene subfamily. In this work, we examined the
pparalpha gene repertoire in brown trout, Salmo trutta f. fario. Data disclosed
two pparalpha-like sequences in brown trout. Phylogenetic analyses further
revealed that the isolated genes are most likely genome pparalphaB duplicates,
pparalphaBa and pparalphaBb, while pparalphaA is apparently absent in salmonids.
Both genes showed a ubiquitous mRNA expression across a panel of 11 different
organs. In vitro exposed primary brown trout hepatocytes strongly suggest that
pparalpha gene paralogues are differently regulated by ethinylestradiol (EE2).
PparalphaBb mRNA expression significantly decreased with dosage, reaching
significance after exposure to 50MUM EE2, while pparalphaBa mRNA increased,
significant at 1MUM EE2. The present data enhances the understanding of pparalpha
function and evolution in teleost, and reinforces the evidence of a potential
crosstalk between estrogenic and pparalpha signaling pathways.
PMID- 28414177
TI - The acitretin and methotrexate combination therapy for psoriasis vulgaris
achieves higher effectiveness and less liver fibrosis.
AB - Both acitretin and methotrexate are effective in ameliorating psoriatic lesion.
However, their combination has been seldom reported in the treatment of psoriasis
because of the warning regarding the potential hepatotoxicity of the drug
interactions. This study was designed to investigate the effectiveness of such
combination therapy for psoriasis vulgaris, and the potential benefit as well as
side effect during the treatment. Thirty-nine patients with psoriasis vulgaris
were treated with acitretin, methotrexate or their combination or as control.
Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs.
Human primary keratinocytes and hepatic stellate cells were used for analyzing
their effect in vitro. The results showed that the combination therapy exhibited
higher effectiveness in remitting skin lesion, but did not significantly affect
the liver function of both patients and mice. Moreover, the combination groups
showed less elevation of profibrotic factors in sera when compared with
methotrexate alone groups accordingly. Furthermore, primary keratinocytes
expressed more involucrin as well as loricrin and proliferated more slowly on the
combined stimulation. Interestingly, such combination treatment induced lower
expression of profibrotic factors in hepatic stellate cells. In conclusion, the
acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve
higher effectiveness and result in less liver fibrosis.
PMID- 28414178
TI - Short- and long-term effects of risperidone on catalepsy sensitisation and
acquisition of conditioned avoidance response: Adolescent vs adult rats.
AB - The effects of antipsychotic drugs (APDs) on the adolescent brain are poorly
understood despite a dramatic increase in prescription of these drugs in
adolescents over the past twenty years. Neuronal systems continue to be remodeled
during adolescence. Therefore, when given in adolescence, antipsychotic drugs
(APDs) have the potential to affect this remodeling. In this study we
investigated the effects of chronic 22-day risperidone treatment (1.3mg/kg/day)
in both adolescent and adult rats. We examined short- and long-term changes in
behaviour (catalepsy, locomotion and conditioned avoidance response (CAR)), and
dopaminergic and serotonergic neurochemistry in the striatum and the nucleus
accumbens. Here, we report that, both during chronic treatment and after a
lengthy drug-free interval, risperidone induced a sensitised cataleptic response
regardless of the age of exposure. Selectively in adolescents, risperidone
induced catalepsy was inversely correlated with striatal dopamine turnover
immediately after chronic treatment. After a drug-free interval, a significant
proportion of rats with prior adolescent risperidone treatment also failed to
acquire CAR to a defined criterion. Our data provide evidence that the same
chronic risperidone treatment regimen can induce contrasting short- and long-term
neural outcomes in the adolescent and adult brains.
PMID- 28414179
TI - Alteration of B cell subsets and the receptor for B cell activating factor (BAFF)
in paediatric patients with type 1 diabetes.
AB - BACKGROUND: Lately, mounting evidence has shown that B cells play an important
role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations
in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of
patients with type 1 diabetes (T1D) and their relatives. PATIENTS AND METHODS: B
cells were studied in 438 patients with T1D (158 at disease onset and 280 with
long-term disease), 136 first-degree relatives and 53 healthy controls. The B
cell panel included transitional, naive, MZ-like, switched memory B cells and
plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on
both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was
analysed in vitro. RESULTS: We observed a significant decrease in the proportion
of transitional B cells in the patients with T1D, accompanied by an increased
proportion of plasmablasts, especially in recent-onset patients and their
relatives. While the BAFF serum levels did not differ in the patients with T1D,
BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort,
with the exception of patients with recent-onset disease who exhibited a
significant increase in the number of BAFFR-expressing T cells. T cell activation
and B cell proliferation were more pronounced after activation with BAFF in the
T1D cohort compared to controls. CONCLUSION: The B cell panel in patients with
T1D is characterized by significantly reduced populations of B cells in their
early stages of development with a shift towards plasma cells. The dynamics of
BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D
T cells to BAFF point to the role of BAFF and T and B cell cooperation in the
development of T1D.
PMID- 28414180
TI - Serum TNF-alpha concentrations in type 2 diabetes mellitus patients and diabetic
nephropathy patients: A systematic review and meta-analysis.
AB - OBJECTIVES: The aim of this study was to investigate whether the concentrations
of serum tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine,
increased in type 2 diabetes mellitus (T2DM) and type 2 diabetic nephropathy
(T2DN) patients. METHODS: The four databases (PubMed, CNKI, WanFang and Chinese
Cqvip) were searched from Jan 1, 1999 to October 1, 2016 for all clinical case
control studies about the serum TNF-alpha concentrations in T2DM and T2DN
patients. All relevant data were extracted from published reports. The meta
analysis was performed to compare the changes of serum TNF-alpha concentrations
of T2DN and T2DM patients in Eastern and Western with healthy controls. We
further evaluated concentrations of serum TNF-alpha in T2DN patients with
mincroalbuminuria or macroalbuminuria. Random-effects models were adopted to
assess the pooling data among various variations. RESULTS: In total of 6 studies
(744 patients and 277 healthy controls) were included in this study. Compared
with healthy controls (both p<0.01), the groups of different albuminuria levels
and ethnicities both showed that the serum TNF-alpha levels were significantly
elevated in T2DN patients as well as in eastern T2DN patients (p=0.001), but not
significant changed in western T2DN patients (p=0.081). The results were stable
through sensitivity analysis and no significant publications bias existed in this
meta-analysis. CONCLUSIONS: Serum TNF-alpha concentrations are obviously
increased in T2DN and T2DM patients, but higher in T2DN patients, suggesting an
elevated inflammatory burden in T2DN patients.
PMID- 28414181
TI - Myeloid but not plasmacytoid blood DCs possess Th1 polarizing and Th1/Th17
recruiting capacity in psoriasis.
AB - Psoriasis is a common inflammatory skin disease and dendritic cells (DCs) play
crucial role in the development of skin inflammation. Although the
characteristics of skin DCs in psoriasis are well defined, less is known about
their peripheral blood precursors. Our aim was to characterize the phenotypic
features as well as the cytokine and chemokine production of CD1c+ myeloid DCs
(mDCs) and plasmacytoid DCs (pDCs) in the blood samples of psoriatic patients.
Blood DCs were isolated by using a magnetic separation kit, and their
intracytoplasmic cytokine production and CD83/CD86 maturation/activation marker
expression were investigated by 8-colour flow cytometry. In CD1c+ mDCs the
intracellular productions of Th1, Th2, Th17, Th22 and Treg polarizing cytokines
were examined simultaneously, whereas in pDCs the amounts of IFNalpha as well as
IL-12, IL-23 and IL-6 were investigated. The chemokine production of both DC
populations was investigated by flow-cytometry and ELISA. According to our
results psoriatic CD1c+ mDCs were in a premature state since their CD83/CD86
maturation/activation marker expression, IL-12 cytokine, CXCL9 and CCL20
chemokine production was significantly higher compared to control cells. On the
other hand, blood pDCs neither produced any of the investigated cytokines and
chemokines nor expressed CD83/CD86 maturation/activation markers. Our results
indicate that in psoriasis not only skin but also blood mDCs perform Th1
polarizing and Th1/Th17 recruiting capacity, while pDCs function only in the skin
milieu.
PMID- 28414182
TI - Innate lymphoid cells and their stromal microenvironments.
AB - In addition to the interaction between antigen presenting cells, T and B
lymphocytes, recent studies have revealed important roles for a diverse set of
auxiliary cells that profoundly influence the induction and regulation of immune
responses against pathogens. Of these the stromal cells composed of various non
hematopoietic constituents are crucial for the creation and maintenance of
specialized semi-static three-dimensional lymphoid tissue microenvironment,
whereas the more recently described innate lymphoid cells are generated by the
diversification of committed lymphoid precursor cells independently from clonally
rearranged antigen receptor genes. Recent findings have revealed important
contributions by innate lymphoid cells in inflammation and protection against
pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also
influence the onset of immune responses in tissue-specific fashion, raising the
possibility of tissue-specific stromal - innate lymphoid cell collaboration. In
this review we summarize the main features and interactions between these two
cells types, with particular emphasis on ILC type 3 cells and their
microenvironmental partners.
PMID- 28414183
TI - NKG2D: A versatile player in the immune system.
AB - NKG2D is known as a potent activating receptor of the immune system. It is
expressed on a multitude of immune cells, including NK cells and different
subsets of T cells. NKG2D recognizes various MHC I-like ligands that are induced
on target cells exposed to stressors such as viral infection, DNA damage and
oncological transformation. NKG2D drives or facilitates cytotoxic and cytokine
responses towards cells expressing its ligands to eliminate the threat.
Therefore, NKG2D is usually classified as a sensor that translates cellular
stress into activation signals for immune cells. However, more recently it has
become evident that NKG2D plays a role beyond direct killing of target cells.
Lack of NKG2D affects development of NK cells in the bone marrow, resulting in
hyperreactive NK cells. NKG2D deficiency on CD8 T cells affects the ability of
effector cells to produce cytokines in response to T cell receptor engagement and
reduces their capacity to establish immunological memory. Although NKG2D is not
expressed on B cells subsets, lack of this receptor in hematopoietic precursors
affects B cell development. Homing of mature B2 cells is altered in NKG2D
deficient mice and they have a strong reduction in peripheral B1a cell numbers,
resulting in increased susceptibility to bacterial infections. The exact
molecular mechanisms via which NKG2D mediates these versatile functions is still
being explored, but appears to depend on the control of activation thresholds,
either in hematopoietic precursors or mature immune cell subsets. In this review,
we will elaborate on the underappreciated developmental and regulatory roles of
NKG2D.
PMID- 28414184
TI - Mouse cytomegalovirus encoded immunoevasins and evolution of Ly49 receptors -
Sidekicks or enemies?
AB - Cytomegaloviruses (CMVs) have dedicated a large portion of their genome towards
immune evasion targeting many aspects of the host immune system, particularly NK
cells. However, the host managed to cope with the infection by developing
multiple mechanisms to recognize viral threat and counterattack it, thus
illustrating never-ending evolutionary interplay between CMV and its host. In
this review, we will focus on several mechanisms of NK cell evasion by mouse CMV
(MCMV), the role of host inhibitory and activating Ly49 receptors involved in the
virus control and acquisition of adaptive features by NK cells as a consequence
of MCMV infection.
PMID- 28414185
TI - Individual differences in the dominance of interhemispheric connections predict
cognitive ability beyond sex and brain size.
AB - Global structural brain connectivity has been reported to be sex-dependent with
women having increased interhemispheric connectivity (InterHc) and men having
greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show
greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on
average, smaller brains than men. Therefore, sex differences in brain size may
modulate sex differences in global brain connectivity. At the behavioural level,
sex-dependent differences in connectivity are thought to contribute to men-women
differences in spatial and verbal abilities. But this has never been tested at
the individual level. The current study assessed whether individual differences
in global structural connectome measures (InterHc, IntraHc and the ratio of
InterHc relative to IntraHc) predict spatial and verbal ability while accounting
for the effect of sex and brain size. The sample included forty men and forty
women, who did neither differ in age nor in verbal and spatial latent components
defined by a broad battery of tests and tasks. High-resolution T1-weighted and
diffusion-weighted images were obtained for computing brain size and
reconstructing the structural connectome. Results showed that men had higher
IntraHc than women, while women had an increased ratio InterHc/IntraHc. However,
these sex differences were modulated by brain size. Increased InterHc relative to
IntraHc predicted higher spatial and verbal ability irrespective of sex and brain
size. The positive correlations between the ratio InterHc/IntraHc and the spatial
and verbal abilities were confirmed in 1000 random samples generated by
bootstrapping. Therefore, sex differences in global structural connectome
connectivity were modulated by brain size and did not underlie sex differences in
verbal and spatial abilities. Rather, the level of dominance of InterHc over
IntraHc may be associated with individual differences in verbal and spatial
abilities in both men and women.
PMID- 28414187
TI - Metatropic dysplasia in third trimester of pregnancy and a novel causative
variant in the TRPV4 gene.
AB - Prenatal diagnosis of skeletal dysplasias is particularly difficult for many
reasons and differentiating these disorders in the prenatal period can be
challenging because they are rare and many of the ultrasound findings are not
necessarily pathognomonic for a specific disorder. The diagnosis is often made
just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is
based predominantly upon fetal ultrasound findings and it focuses substantially
on the possible lethality of the disorder, without always being able to find a
specific name for the disorder. Metatropic dysplasia is a rare
osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation
channel, non-selectively permeable to calcium, encoded by a gene on chromosome
12q24.11; it is widely expressed and involved in many different physiological
processes through responses to several different stimuli (physical, chemical, and
hormonal) in ciliated epithelial cells. The exact incidence of this disorder is
not known, however less than a hundred cases have been reported at present, with
only two prenatal reports but without any reference to the molecular test. We
describe the first report of molecular diagnosis of metatropic dysplasia carried
out in prenatal diagnosis: the molecular testing of the TRPV4 (transient receptor
potential cation channel, subfamily V, member 4, MIM *605427) gene in our case,
in fact, detected a causative variant, confirming the diagnostic suspicion, which
was made possible thanks also to the utilization of MRI and CT scan. In our case
different imaging methods together with the close cooperation of a
multidisciplinary team and test availability, allowed an accurate diagnosis.
PMID- 28414188
TI - A case of splenomegaly in CBL syndrome.
AB - INTRODUCTION: We present a child with unexplained splenomegaly to highlight this
feature as a presenting sign of the RASopathy CBL syndrome and to draw attention
to the power and utility of next generation genomic sequencing for providing
rapid diagnosis and critical information to guide care in the pediatric clinical
setting. CLINICAL REPORT: A 7-year-old boy presented with unexplained
splenomegaly, attention deficit hyperactivity disorder, mild learning
difficulties, easy bruising, mild thrombocytopenia, and subtle dysmorphic
features. Extensive haematological testing including a bone marrow biopsy showed
mild megaloblastoid erythropoiesis and borderline fibrosis. There were no
haematological cytogenetic anomalies or other haematological pathology to explain
the splenomegaly. Metabolic testing and chromosomal microarray were unremarkable.
Trio whole-exome sequencing (WES) identified a pathogenic de novo heterozygous
germline CBL variant (c.1111T > C, p.Y371H), previously reported to cause CBL
syndrome and implicated in development of juvenile myelomonocytic leukemia
(JMML). DISCUSSION: CBL syndrome (more formally known as "Noonan-syndrome-like
disorder with or without juvenile myelomonocytic leukemia") has overlapping
features to Noonan syndrome with significant variability. CBL syndrome and other
RASopathy disorders-including Noonan syndrome, neurofibromatosis 1, and Costello
syndrome-are important to recognize as these are associated with a cancer
predisposition. CBL syndrome carries a very high risk for JMML, thus accurate
diagnosis is of utmost importance. The diagnosis of CBL syndrome in this patient
would not have been possible based on clinical features alone. Through WES, a
specific genetic diagnosis was made, allowing for an optimized management and
surveillance plan, illustrating the power of genomics in clinical practice.
PMID- 28414189
TI - Radioiodinated hypericin disulfonic acid sodium salts as a DNA-binding probe for
early imaging of necrotic myocardium.
AB - Necrotic myocardium imaging can provide great indicators of salvaged myocardial
areas for clinical guidances to patients with myocardial infarction (MI). One of
the key challenges in necrotic myocardium imaging however, is lack of ideal
necrotic imaging tracers for exactly and timely depicting the necrotic
myocardium. 131I-hypericin (131I-Hyp) is a promising tracer in exact necrotic
myocardium delineation. However, it can't clearly image necrotic myocardium until
9h post injection (p.i.) for the high background signals in blood and lung due to
the strong lipophilicity. Herein, an optimized 131I-hypericin-2,5-disulfonic acid
sodium salts (131I-Shyp) probe was synthesized for better pharmacokinetic and
biodistribution properties to necrosis imaging. And the related mechanisms of
necrotic avidity ability of 131I-Hyp and 131I-Shyp were also explored. In the
results, 131I-Shyp still showed selectively high accumulation in both necrotic
cells and tissues. Biodistribution data revealed the decreased uptake of 131I
Shyp in normal organs (lung, spleen and heart) and blood (as shown in
pharmacokinetics studies). 131I-Shyp presented quicker and clearer imaging for
necrotic myocardium at 4h p.i. compared with 131I-Hyp, suggesting that improved
hydrophilicity of 131I-Shyp may be conducive to its better pharmacokinetic and
biodistribution properties to imaging. Additionally, DNA competitive binding
assays and blocking experiments indicated that E-DNA is the possible target of
Shyp and Hyp for their necrosis avidity. 131I-Shyp may serve as a potential E-DNA
targeted probe for necrotic myocardium imaging with molecular specificity for
clinical use.
PMID- 28414186
TI - A review on neuroimaging-based classification studies and associated feature
extraction methods for Alzheimer's disease and its prodromal stages.
AB - Neuroimaging has made it possible to measure pathological brain changes
associated with Alzheimer's disease (AD) in vivo. Over the past decade, these
measures have been increasingly integrated into imaging signatures of AD by means
of classification frameworks, offering promising tools for individualized
diagnosis and prognosis. We reviewed neuroimaging-based studies for AD and mild
cognitive impairment classification, selected after online database searches in
Google Scholar and PubMed (January, 1985-June, 2016). We categorized these
studies based on the following neuroimaging modalities (and sub-categorized based
on features extracted as a post-processing step from these modalities): i)
structural magnetic resonance imaging [MRI] (tissue density, cortical surface,
and hippocampal measurements), ii) functional MRI (functional coherence of
different brain regions, and the strength of the functional connectivity), iii)
diffusion tensor imaging (patterns along the white matter fibers), iv)
fluorodeoxyglucose positron emission tomography (FDG-PET) (metabolic rate of
cerebral glucose), and v) amyloid-PET (amyloid burden). The studies reviewed
indicate that the classification frameworks formulated on the basis of these
features show promise for individualized diagnosis and prediction of clinical
progression. Finally, we provided a detailed account of AD classification
challenges and addressed some future research directions.
PMID- 28414190
TI - Engineered polymeric microspheres obtained by multi-step method as potential
systems for transarterial embolization and intraoperative imaging of HCC:
Preliminary evaluation.
AB - The aim of this study was the development of novel fluorescent microspheres as
embolic agent for transarterial embolization (TAE) of advanced stages of
hepatocellular carcinoma (HCC). TAE is a minimally invasive procedure that
induces tumour regression blocking the blood flow by injection of microparticles.
The microspheres currently used in clinical application cannot be visualized in
vivo. Surgeon could exploit the intraoperative detection of embolic agents during
resection of the malignant mass. Biocompatible indocyanine green (ICG)-loaded
microspheres (CAB-CS-ICG) were prepared using a multi-step method. Chitosan (CS)
ICG particles were prepared via spray-dryer and then loaded into cellulose
acetate butyrate (CAB) microspheres, fabricated by emulsion solvent extraction
method. Technological parameters such as yield, size, encapsulation efficiency
and morphology were studied. CAB-CS-ICG microspheres showed spherical shape and
smooth surface, as well as good injectability through a 21 G*11/2 needle. ICG
release from CAB-CS-ICG was very low due to the strong interaction between CS and
ICG. This result was also confirmed by in vitro fluorescence imaging studies,
conducted using Photodynamic Eye (PDE) for the detection of particles incubated
in human plasma. CAB-CS-ICG were capable to maintain the fluorescence selectivity
for 4weeks. Our data suggested the potential usefulness of CAB-CS-ICG in TAE
application as embolic agents and following imaging of tumour during surgical
procedure.
PMID- 28414191
TI - Instant ODFs - Development of an intermediate, nanoparticle-based product
platform for individualized medication.
AB - The individualization of solid dosage forms to realize a flexible therapy for all
patient groups is a topic which increasingly gains importance in pharmaceutical
research. The goal of this study was to develop a nanoparticulate, instant
orodispersible film (iODF) powder which can easily be reconstituted in water to
cast ODFs containing an individualized concentration of an active pharmaceutical
ingredient (API). It was shown that the processing of the film casing mass to
iODF powders by spray drying provides the same advantageous film properties,
particles sizes redispersed from the ODF and dissolution profiles as compared to
the common production route. Due to the realization of nanoparticle loads up to
50wt.% in the iODF powders, high API loads (11.8mgcm-2) are achieved in final
ODFs. The powders are well storable at different temperatures for at least three
months and do not change their crystalline state during storage. Furthermore,
dissolution of a defined amount of API from ODFs was found to be the fastest with
the highest drug loads in the films.
PMID- 28414192
TI - Congenital erythroderma should be considered as an urgent warning sign of
immunodeficiency: a case of Omenn syndrome.
PMID- 28414193
TI - Generalized lichen nitidus-like eruption in the setting of mogamulizumab and
tremelimumab.
PMID- 28414194
TI - Maculopapular rash during a nadir period in a patient with acute myeloid
leukaemia.
PMID- 28414195
TI - Tegafur/gimeracil/oteracil (TS-1)-induced erythroderma with an extensive mucosal
involvement and hand-foot syndrome.
PMID- 28414196
TI - A cream based on Aquaphilus dolomiae extracts alleviates non-histaminergic
pruritus in humans.
PMID- 28414197
TI - Engineering of a self-adjuvanted iTEP-delivered CTL vaccine.
AB - Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in
cancer and infectious disease therapy. We previously generated an immune-tolerant
elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine
and enhance the efficiency of the vaccine. To further optimize the vaccine
carrier, we intended to potentiate its function by designing an iTEP-based
carrier that was able to deliver adjuvant and a vaccine epitope as one molecule.
Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1
protein (HMGB1) that could induce activation of dendritic cells (DCs), with an
iTEP polymer to generate a new iTEP polymer named H100-iTEP. The H100-iTEP still
kept the feature of reversible phase transition of iTEPs and should be able to be
used as a polymer carrier to deliver peptide vaccines. The expression levels of
CD80/CD86 on DCs were assessed using flow cytometry. The iTEP fusion-stimulated
IL-6 secretion by DCs was measured with ELISA. Activation of antigen-specific
CD8+ T cells induced by iTEP fusions was examined through a B3Z hybridoma cell
activation assay. In vivo CTL activation promoted by iTEP fusions was detected by
an IFN-gamma-based ELISPOT assay. The iTEP fused with H100 could induce
maturation of DCs in vitro as evidenced by increased CD80 and CD86 expression.
The iTEP fusion also promoted activation of DCs by increasing secretion of a
proinflammatory cytokine IL-6. The N-terminus or C-terminus fusion of H100 to
iTEP had a similar effect and a reduced form of cysteine in iTEP fusions was
required for DC stimulation. iTEP fusions potentiated a co-administrated CTL
vaccine by increasing an antigen-specific CTL response in vitro and in vivo. When
the H100-iTEP was fused to a CTL epitope to generate a one-molecule vaccine, this
self-adjuvanted vaccine elicited a stronger antigen-specific CTL response than a
vaccine adjuvanted by Incomplete Freund's Adjuvant. Thus, we have successfully
generated a functional, one-molecule iTEP-based self-adjuvanted vaccine.
PMID- 28414198
TI - LY333531, a PKCbeta inhibitor, attenuates glomerular endothelial cell apoptosis
in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1.
AB - Glomerular endothelial cell (GEC) injury plays an important role in the early
stage of diabetic nephropathy (DN). Previous studies show that a PKCbeta
inhibitor is effective for treating DN. In the current study we further explored
the effects and molecular mechanisms of PKCbeta inhibitors on GEC apoptosis in DN
in streptozotocin-induced diabetic mice in vivo and high glucose- or PMA-treated
human renal glomerular endothelial cells (HRGECs) in vitro. In the diabetic mice,
hyperglycemia caused aggravated nephropathy and GEC apoptosis accompanied by
significantly increased expression of swiprosin-1, a potentally pro-apoptotic
protein. Administration of LY333531 (1 mg.kg-1.d-1 for 8 weeks) significantly
attenuated both GEC apoptosis and swiprosin-1 upregulation in the diabetic mice.
Similar results were observed in high glucose- or PMA-treated HRGECs in vitro.
The pro-apoptotic role of swiprosin-1 was further examined using HRGECs treated
with lentivirus mediating RNA interference or over-expression and swiprosin-1
knockout mice. Over-expression of swiprosin-1 in HRGECs resulted in increases in
apoptosis and in caspase-9, caspase-3 and Bax expression. In contrast, knockdown
of swiprosin-1 attenuated high glucose- or PMA-induced HRGECs apoptosis.
Furthermore, over-expression of swiprosin-1 promoted interaction between
swiprosin-1 and caspase-9 and increased the formation of apoptosomes. In diabetic
swiprosin-1-/- mice, the kidney/body weight, urinary albumin, glomerular
hypertrophy, mitochondrial apoptotic-associated proteins and GEC apoptosis were
significantly attenuated as compared with those in diabetic swiprosin-1+/+ mice.
These results demonstrate that swiprosin-1 is up-regulated by PKCbeta in the
early stage of DN, and that PKCbeta facilitates GEC apoptosis through the
mitochondrial-dependent pathway.
PMID- 28414199
TI - Structure of the PRC2 complex and application to drug discovery.
AB - The polycomb repressive complexes 2 (PRC2) complex catalyzes tri-methylation of
histone H3 lysine 27 (H3K27), a repressive chromatin marker associated with gene
silencing. Overexpression and mutations of PRC2 are found in a wide variety of
cancers, making the catalytic activity of PRC2 an important target of cancer
therapy. This review highlights recent structural breakthroughs of the human PRC2
complex bound to the H3K27 peptide and a small molecule inhibitor, which provide
critically needed insight into PRC2-targeted drug discovery.
PMID- 28414200
TI - Combining 53BP1 with BRCA1 as a biomarker to predict the sensitivity of poly(ADP
ribose) polymerase (PARP) inhibitors.
AB - Over half of patients with BRCA1-deficient cancers do not respond to treatment
with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that
a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor
sensitivity. Based on the mRNA levels of four homologous recombination repair
(HR) genes and PARP inhibitor sensitivity, we selected BRCA1-deficient MDA-MB-436
cells to conduct RNA interference. Reducing expression of 53BP1, but not the
other three HR genes, was found to lower simmiparib sensitivity. Additionally, we
generated 53BP1-/-/BRCA1-/- clonal variants by the transcription activator-like
effector nuclease (TALEN) technique and found that depleting 53BP1 impaired PARP
inhibitor sensitivity with a 36.7-fold increase in their IC50 values. Consistent
with its effect on PARP inhibitor sensitivity, 53BP1 loss alleviated cell cycle
arrest and apoptosis and partially restored HR function. Importantly, 53BP1
depletion dramatically reduced the ability of PARP inhibitors to suppress tumor
growth in vivo. The inhibition rate of simmiparib was 74.16% for BRCA1-deficient
MDA-MB-436 xenografts, but only 7.79% for 53BP1/BRCA1-deficient xenografts. Re
expressing 53BP1 in the dual-deficient cells restored PARP inhibitor sensitivity
and the levels of HR regulators. Considering that at least 10% of BRCA1-deficient
breast and ovarian cancers have reduced expression of 53BP1, using a combination
of 53BP1 with BRCA1 as a biomarker for patient selection should reduce the number
of patients undergoing futile treatment with PARP inhibitors.
PMID- 28414201
TI - Intrinsic radiolabeling of Titanium-45 using mesoporous silica nanoparticles.
AB - Titanium-45 (45Ti) with a three-hour half-life (t1/2=3.08 h), low maximum
positron energy and high positron emission branching ratio, is a suitable
positron emission tomography (PET) isotope whose potential has not yet been fully
explored. Complicated radiochemistry and rapid hydrolysis continue to be major
challenges to the development of 45Ti compounds based on a traditional chelator
based radiolabeling strategy. In this study we introduced an intrinsic (or
chelator-free) radiolabeling technique for the successful labeling of 45Ti using
mesoporous silica nanoparticle (MSN). We synthesized uniform MSN with an average
particle size of ~150 nm in diameter. The intrinsic 45Ti-labeling was
accomplished through strong interactions between 45Ti (hard Lewis acid) and hard
oxygen donors (hard Lewis bases), the deprotonated silanol groups (-Si-O-) from
the outer surface and inner meso-channels of MSN. In vivo tumor-targeted PET
imaging of as-developed PEGylated [45Ti]MSN was further demonstrated in the 4T1
murine breast tumor-bearing mice. This MSN-based intrinsic radiolabeling strategy
could open up new possibilities and speed up the biomedical applications of 45Ti
in the future.
PMID- 28414202
TI - Recent advances in peptide nucleic acid for cancer bionanotechnology.
AB - Peptide nucleic acid (PNA) is an oligomer, in which the phosphate backbone has
been replaced by a pseudopeptide backbone that is meant to mimic DNA. Peptide
nucleic acids are of the utmost importance in the biomedical field because of
their ability to hybridize with neutral nucleic acids and their special chemical
and biological properties. In recent years, PNAs have emerged in
nanobiotechnology for cancer diagnosis and therapy due to their high affinity and
sequence selectivity toward corresponding DNA and RNA. In this review, we
summarize the recent progresses that have been made in cancer detection and
therapy with PNA biotechnology. In addition, we emphasize nanoparticle PNA-based
strategies for the efficient delivery of drugs in anticancer therapies.
PMID- 28414204
TI - Docking-based structural splicing and reassembly strategy to develop novel
deazapurine derivatives as potent B-RafV600E inhibitors.
AB - The mutation of B-RafV600E is widespread in a variety of human cancers. Its
inhibitors vemurafenib and dabrafenib have been launched as drugs for treating
unresectable melanoma, demonstrating that B-RafV600E is an ideal drug target.
This study focused on developing novel B-RafV600E inhibitors as drug leads
against various cancers with B-RafV600E mutation. Using molecular modeling
approaches, 200 blockbuster drugs were spliced to generate 283 fragments followed
by molecular docking to identify potent fragments. Molecular structures of
potential inhibitors of B-RafV600E were then obtained by fragment reassembly
followed by docking to predict the bioactivity of the reassembled molecules. The
structures with high predicted bioactivity were synthesized, followed by in vitro
study to identify potent B-RafV600E inhibitors. A highly potent fragment binding
to the hinge area of B-RafV600E was identified via a docking-based structural
splicing approach. Using the fragment, 14 novel structures were designed by
structural reassembly, two of which were predicted to be as strong as marketed B
RafV600E inhibitors. Biological evaluation revealed that compound 1m is a potent
B-RafV600E inhibitor with an IC50 value of 0.05 MUmol/L, which was lower than
that of vemurafenib (0.13 MUmol/L). Moreover, the selectivity of 1m against B
RafWT was enhanced compared with vemurafenib. In addition, 1m exhibits desirable
solubility, bioavailability and metabolic stability in in vitro assays. Thus, a
highly potent and selective B-RafV600E inhibitor was designed via a docking-based
structural splicing and reassembly strategy and was validated by medicinal
synthesis and biological evaluation.
PMID- 28414203
TI - Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin
for efficient tumor-targeted chemotherapy.
AB - Since the discovery that nano-scaled particulates can easily be incorporated into
tumors via the enhanced permeability and retention (EPR) effect, such
nanostructures have been exploited as therapeutic small molecule delivery
systems. However, the convoluted synthetic process of conventional nanostructures
has impeded their feasibility and reproducibility in clinical applications.
Herein, we report an easily prepared formulation of self-assembled nanostructures
for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic
acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride).
pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong
interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three
nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of
1:1, 2:1, and 4:1, respectively, to investigate the function of the residual PBA
moiety as a targeting ligand. An acid-labile drug release profile was observed,
owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor
targeting ability of the nanocomplexes was demonstrated, both in vitro by
confocal microscopy and in vivo by fluorescence imaging, to be driven by an
inherent property of the residual PBA. Ligand competition assays with free PBA
pre-treatment demonstrated the targeting effect of the residual PBA from the
nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free
DOX, exhibited significantly greater anti-cancer effects in vitro and even in
vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled
nanostructures with potential biomedical applications.
PMID- 28414205
TI - Molecular tumor targeting of gelonin by fusion with F3 peptide.
AB - Therapeutically potent macromolecular drugs have shown great promise for
overcoming the limitations of small-molecule anti-cancer drugs. But tumor cell
selective intracellular delivery of the macromolecules remains a major hurdle for
their successful clinical application. To overcome this challenge, we engineered
a novel genetic fusion protein (F3-Gel) that composed of F3 peptide, a tumor
homing peptide, and gelonin, a plant-derived ribosome-inactivating protein (RIP),
and then evaluated its anti-cancer activity in vitro and in vivo. The F3-Gel
encoding gene was synthesized by genetic recombination, and F3-Gel was
successfully expressed in E coli. The anti-cancer activity of the produced F3-Gel
was evaluated by various in vitro assays, which revealed that F3-Gel maintained
equipotent protein synthesis inhibition activity (IC50=11 pmol/L) as unmodified
gelonin (IC50=10 pmol/L). Furthermore, F3-Gel displayed enhanced cellular uptake
into cancer cells (U87 MG, HeLa, LnCaP and 9L) than noncancerous cells (293 HEK
and SVGp12). Compared with gelonin, F3-Gel exerted significantly higher
cytotoxicity against these cancer cells. F3-Gel displayed significantly greater
inhibition of protein translation in U87 MG cells: F3-Gel (0.5 MUmol/L) was able
to reduce the protein level to less than 50%, while gelonin (1 MUmol/L) did not
affect the intracellular protein level. In a U87 MG xenograft tumor-bearing mouse
model, F3-Gel was accumulated in the tumor site at much higher levels and
maintained for a prolonged time compared with gelonin. Administration of F3-Gel
(0.5, 0.75 mol/kg, iv) caused 36% and 66%, respectively, inhibition of tumor
growth in U87 MG xenograft mice, suggesting that it is a promising candidate drug
for cancer treatment. Furthermore, this study demonstrates that fusion of F3
peptide to a potent macromolecule could provides an effective method for
targeting tumors and eventually could improve their druggability.
PMID- 28414206
TI - Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in
a mouse Xenograft model.
AB - Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an
adjuvant for the prevention of bone metastases in breast cancer patients. In this
study we investigated the efficacy of WSZG in preventing bone metastases and the
potential mechanisms in a mouse xenograft model of breast cancer bone metastases.
This model was established by injection of human MDA-MB-231BO-Luc breast cancer
cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal
stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the
mice were treated with WSZG (3.25, 6.5 or 13.0 mg.kg-1.d-1, ig) for four weeks,
whereas zoledronic acid (100 MUg/kg per week, ig) was used as a positive control.
The occurrence and development of bone metastases were monitored via
bioluminescent imaging, and bone lesions were assessed using micro-CT.
Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells
with BMSCs significantly facilitated the bone metastatic capacity of the breast
cancer cells, and aggravated bone lesions in the mouse xenograft model of breast
cancer bone metastases. Administration of WSZG dose-dependently inhibited the
incidence and intensity of bone metastases and protected against bone lesions by
suppressing osteoclast formation and tumor cell infiltration. Furthermore,
administration of WSZG caused a marked reduction in the expression of CCL5/CCR5
and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG
exerts potential therapeutic effects in a mouse xenograft model of breast cancer
bone metastases, which are partially mediated by weakening the interaction
between BMSCs and breast cancer cells in the tumor microenvironment.
PMID- 28414208
TI - Highly Compressible Nitrogen-Doped Carbon Foam Electrode with Excellent Rate
Capability via a Smart Etching and Catalytic Process.
AB - Freestanding three-dimensional nitrogen-doped carbon foam with large pores is
proposed as a promising electrode configuration for elastic electronics. Although
it exhibits excellent mechanical performance, the capacitive performances
(especially its rate capability) are still unsatisfactory. By using KMnO4, we
demonstrate a smart etching and catalytic process to form highly graphitized and
etched nitrogen-doped carbon foam (ENCF) with an exfoliated carbon-shell
architecture. These compositional and structural features endow the ENCF
electrodes with excellent electron conductivity as well as more ion-accessible
electrochemical active sites. Significantly, all-solid-state symmetric
supercapacitor devices based on the ENCF electrodes exhibit enhanced specific
capacitance and marked high-rate capability. Furthermore, the integrated device
has no significant capacity loss under 60% compressive strain.
PMID- 28414209
TI - Polypharmacological in Silico Bioactivity Profiling and Experimental Validation
Uncovers Sedative-Hypnotic Effects of Approved and Experimental Drugs in Rat.
AB - In this work, we describe the computational ("in silico") mode-of-action analysis
of CNS-active drugs, which is taking both multiple simultaneous hypotheses as
well as sets of protein targets for each mode-of-action into account, and which
was followed by successful prospective in vitro and in vivo validation. Using
sleep-related phenotypic readouts describing both efficacy and side effects for
491 compounds tested in rat, we defined an "optimal" (desirable) sleeping
pattern. Compounds were subjected to in silico target prediction (which was
experimentally confirmed for 21 out of 28 cases), followed by the utilization of
decision trees for deriving polypharmacological bioactivity profiles. We
demonstrated that predicted bioactivities improved classification performance
compared to using only structural information. Moreover, DrugBank molecules were
processed via the same pipeline, and compounds in many cases not annotated as
sedative-hypnotic (alcaftadine, benzatropine, palonosetron, ecopipam,
cyproheptadine, sertindole, and clopenthixol) were prospectively validated in
vivo. Alcaftadine, ecopipam cyproheptadine, and clopenthixol were found to
promote sleep as predicted, benzatropine showed only a small increase in NREM
sleep, whereas sertindole promoted wakefulness. To our knowledge, the sedative
hypnotic effects of alcaftadine and ecopipam have not been previously discussed
in the literature. The method described extends previous single-target, single
mode-of-action models and is applicable across disease areas.
PMID- 28414207
TI - Defining the minimum substrate and charge recognition model of gamma-secretase.
AB - gamma-Secretase is an intramembrane aspartyl protease that cleaves the C99
fragment of amyloid precursor protein to generate extracellular Abeta peptides.
These peptides can oligomerize and aggregate to form amyloid plaques, processes
that are widely believed to be causal for Alzheimer's disease. In spite of this
critical function, it remains unknown how gamma-secretase recognizes C99 and its
other substrates, including Notch. In this study we determined E22-K55 as the
minimal C99 fragment that was sufficient and required for initial cleavage.
Within this fragment, we identified four determinants: (i) a transferable
extracellular determinant that differed between C99 and Notch, and which included
negative charge in the case of C99, (ii) the amino acid sequence of the C
terminal half of the transmembrane helix, (iii) an invariant lysine or arginine
at the intracellular membrane border, and (iv) a positive charge cluster that
included the invariant lysine/arginine. We demonstrated that the charge clusters
of C99 and Notch receptors could directly bind phosphatidylinositol 4,5
bisphosphate (PIP2). The PIP2-binding cluster was required for gamma-secretase
cleavage, and modulation of membrane PIP2 levels strongly affected gamma
secretase cleavage levels and the Abeta40/Abeta42 ratio, providing support for
the importance of the PIP2 interaction in cells. Together, these studies provide
critically needed insight into substrate recognition by gamma-secretase.
PMID- 28414210
TI - Scalable Production of the Silicon-Tin Yin-Yang Hybrid Structure with Graphene
Coating for High Performance Lithium-Ion Battery Anodes.
AB - Alloy anodes possessed of high theoretical capacity show great potential for next
generation advanced lithium-ion battery. Even though huge volume change during
lithium insertion and extraction leads to severe problems, such as pulverization
and an unstable solid-electrolyte interphase (SEI), various nanostructures
including nanoparticles, nanowires, and porous networks can address related
challenges to improve electrochemical performance. However, the complex and
expensive fabrication process hinders the widespread application of
nanostructured alloy anodes, which generate an urgent demand of low-cost and
scalable processes to fabricate building blocks with fine controls of size,
morphology, and porosity. Here, we demonstrate a scalable and low-cost process to
produce a porous yin-yang hybrid composite anode with graphene coating through
high energy ball-milling and selective chemical etching. With void space to
buffer the expansion, the produced functional electrodes demonstrate stable
cycling performance of 910 mAh g-1 over 600 cycles at a rate of 0.5C for Si
graphene "yin" particles and 750 mAh g-1 over 300 cycles at 0.2C for Sn-graphene
"yang" particles. Therefore, we open up a new approach to fabricate alloy anode
materials at low-cost, low-energy consumption, and large scale. This type of
porous silicon or tin composite with graphene coating can also potentially play a
significant role in thermoelectrics and optoelectronics applications.
PMID- 28414211
TI - Correction to Enhancing Efficiency and Stability of Perovskite Solar Cells
through Nb-Doping of TiO2 at Low Temperature.
PMID- 28414212
TI - Development of 3D Urchin-Shaped Coaxial Manganese Dioxide@Polyaniline (MnO2@PANI)
Composite and Self-Assembled 3D Pillared Graphene Foam for Asymmetric All-Solid
State Flexible Supercapacitor Application.
AB - We have fabricated high-energy-density all-solid-state flexible asymmetric
supercapacitor by using a facile novel 3D hollow urchin-shaped coaxial manganese
dioxide@polyaniline (MnO2@PANI) composite as positive electrode and 3D graphene
foam (GF) as negative electrode materials with polyvinyl alcohol (PVA)/KOH gel
electrolyte. The coaxial MnO2@PANI composite was fabricated by hydrothermal route
followed by oxidation without use of an external oxidant. The formation mechanism
of the 3D hollow MnO2@PANI composite occurs first by nucleation and growth of the
MnO2 crystal species via dissolution-recrystallization and oriented attachment
mechanisms followed by the oxidation of aniline monomers on the MnO2 crystalline
template. The self-assembled 3D graphene block was synthesized by hydrothermal
route using vitamin C as a reducing agent. The microstructures of the composites
are analyzed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
and Raman spectroscopy. The morphology is characterized by field-emission
scanning electron microscopy (FESEM) and transmission electron microscopy (TEM),
which clearly showed the formation of urchin-shaped coaxial MnO2@PANI composite.
The electrochemical studies are explored by cyclic voltammetry, electrochemical
impedance spectrometry, and cyclic charge-discharge tests. The symmetric all
solid-state flexible MnO2@PANI//MnO2@PANI and GF//GF supercapacitors exhibit the
specific capacitance of 129.2 and 82.1 F g-1 at 0.5 A/g current density,
respectively. The solid-state asymmetric supercapacitor shows higher energy
density (37 Wh kg-1) with respect to the solid-state symmetric supercapacitors
MnO2@PANI//MnO2@PANI and GF//GF, where the obtained energy density are found to
be 17.9 and 11.4 Wh kg-1, respectively, at 0.5 A/g current density. Surprisingly,
the asymmetric supercapacitor shows a high energy density of 22.3 Wh kg-1 at a
high current density of 5 A g-1. The solid-state asymmetric supercapacitor shows
a good cyclic stability in which ~11% capacitance loss was observed after 5000
cycles.
PMID- 28414213
TI - Immobilization and Stabilization of Acylase on Carboxylated Polyaniline
Nanofibers for Highly Effective Antifouling Application via Quorum Quenching.
AB - Acylase (AC) was immobilized and stabilized on carboxylated polyaniline
nanofibers (cPANFs) for the development of antifouling nanobiocatalysts with high
enzyme loading and stability. AC was immobilized via three different approaches:
covalent attachment (CA), enzyme coating (EC), and magnetically separable enzyme
precipitate coating (Mag-EPC). The enzyme activity per unit weight of cPANFs with
Mag-EPC was 75 and 300 times higher than that of those with CA and EC,
respectively, representing improved enzyme loading in the form of Mag-EPC. After
incubation under shaking at 200 rpm for 20 days, Mag-EPC maintained 55% of its
initial activity, whereas CA and EC showed 3 and 16% of their initial activities,
respectively. The antifouling of highly loaded and stable Mag-EPC against the
biofouling/biofilm formation of Pseudomonas aeruginosa was tested under static-
and continuous-flow conditions. Biofilm formation in the presence of 40 MUg/mL
Mag-EPC under static condition was 5 times lower than that under control
condition with no addition of Mag-EPC. Under continuous membrane filtration, Mag
EPC delayed the increase of transmembrane pressure (TMP) more effectively as the
concentration of added Mag-EPC increased. When separating Mag-EPC and membranes
in two different vessels under internal circulation of the culture solution, Mag
EPC maintained a higher permeability than the control with no Mag-EPC addition.
It was also confirmed that the addition of Mag-EPC reduced the generation of N
acyl homoserine lactone (AHL) autoinducers. This result reveals that the
inhibition of biofilm formation and biofouling in the presence of Mag-EPC is due
to the hydrolysis of AHL autoinducers, catalyzed by the immobilized and
stabilized AC in the form of Mag-EPC. Mag-EPC of AC with high enzyme loadings and
improved stability has demonstrated its great potential as an antifouling agent
by reducing biofilm formation and membrane biofouling based on "enzymatic quorum
quenching" of autoinducers.
PMID- 28414214
TI - Reconfigurable Complementary Monolayer MoTe2 Field-Effect Transistors for
Integrated Circuits.
AB - Transition metal dichalcogenides are of interest for next generation switches,
but the lack of low resistance electron and hole contacts in the same material
has hindered the development of complementary field-effect transistors and
circuits. We demonstrate an air-stable, reconfigurable, complementary monolayer
MoTe2 field-effect transistor encapsulated in hexagonal boron nitride, using
electrostatically doped contacts. The introduction of a multigate design with
prepatterned bottom contacts allows us to independently achieve low contact
resistance and threshold voltage tuning, while also decoupling the Schottky
contacts and channel gating. We illustrate a complementary inverter and a p-i-n
diode as potential applications.
PMID- 28414215
TI - Highly Sensitive Naked-Eye Assay for Enterovirus 71 Detection Based on Catalytic
Nanoparticle Aggregation and Immunomagnetic Amplification.
AB - Development of sensitive, convenient, and cost-effective virus detection product
is of great significance to meet the growing demand of clinical diagnosis at the
early stage of virus infection. Herein, a naked-eye readout of immunoassay by
means of virion bridged catalase-mediated in situ reduction of gold ions and
growth of nanoparticles, has been successfully proposed for rapid visual
detection of Enterovirus 71 (EV71). Through tailoring the morphologies of the
produced gold nanoparticles (GNPs) varying between dispersion and aggregation, a
distinguishing color changing was ready for observation. This colorimetric
detection assay, by further orchestrating the efficient magnetic enrichment and
the high catalytic activity of enzyme, is managed to realize highly sensitive
detection of EV71 virions with the limit of detection (LOD) down to 0.65 ng/mL.
Our proposed method showed a much lower LOD value than the commercial ELISA for
EV71 virion detection. Comparing to the current clinical gold standard polymerase
chain reaction (PCR) method, our strategy provided the same diagnostic outcomes
after testing real clinical samples. Besides, this strategy has no need of
complicated sample pretreatment or expensive instruments. Our presented naked-eye
immunoassay method holds a promising prospect for the early detection of virus
infectious disease especially in resource-constrained settings.
PMID- 28414217
TI - Selection of Group-Specific Phthalic Acid Esters Binding DNA Aptamers via
Rationally Designed Target Immobilization and Applications for Ultrasensitive and
Highly Selective Detection of Phthalic Acid Esters.
AB - Phthalic acid esters (PAEs) are ubiquitous in the environment, and some of them
are recognized as endocrine disruptors that cause concerns on ecosystem
functioning and public health. Due to the diversity of PAEs in the environment,
there is a vital need to detect the total concentration of PAEs in a timely and
low-cost way. To fulfill this requirement, it is highly desired to obtain group
specific PAE binders that are specific to the basic PAE skeleton. In this study,
for the first time we have identified the group-specific PAE-binding aptamers via
rationally designed target immobilization. The two target immobilization
strategies were adopted to display either the phthalic ester group or the alkyl
chain, respectively, at the surface of the immobilization matrix. The former
enabled the rapid enrichment of aptamers after four rounds of selection. The top
100 sequences are cytosine-rich (44.7%) and differentiate from each other by only
1-4 nucleotides at limited locations. The top two aptamers all display the
nanomolar dissociation constants to both the immobilized target and the free PAEs
[dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), bis(2-ethylhexyl)
phthalate (DEHP)]. We further demonstrate the applications of the aptamers in the
development of high-throughput PAE assays and DEHP electrochemical biosensors
with exceptional sensitivity [limit of detection (LOD), 10 pM] and selectivity
(>105-fold). PAE aptamers targeting one of the most sought for targets thus offer
the promise of convenient, low-cost detection of total PAEs. Our study also
provides insights on the aptamer selection and sensor development of highly
hydrophobic small molecules.
PMID- 28414218
TI - Exploiting the Anti-Aggregation of Gold Nanostars for Rapid Detection of Hand,
Foot, and Mouth Disease Causing Enterovirus 71 Using Surface-Enhanced Raman
Spectroscopy.
AB - Enterovirus 71 (EV71) is a major public health threat that requires rapid point
of-care detection. Here, we developed a surface-enhanced Raman spectroscopy
(SERS)-based scheme that utilized protein-induced aggregation of colloidal gold
nanostars (AuNS) to rapidly detect EV71 without the need for fabricating a solid
substrate, Raman labels or complicated sample handling. We used AuNS
(hydrodynamic diameter, DH of 105.12 +/- 1.13 nm) conjugated to recombinant
scavenger receptor class B, member 2 (SCARB2) protein with known affinity to
EV71. In the absence of EV71, AuNS-SCARB2 aggregated in biological media and
produced four enhanced Raman peaks at 390, 510, 670, and 910 cm-1. In the
presence of EV71, the three peaks at 510, 670, and 910 cm-1 disappeared, while
the peak at 390 cm-1 diminished in intensity as the virus bound to AuNS-SCARB2
and prevented them from aggregation. These three peaks (510, 670, and 910 cm-1)
were potential markers for specific detection of EV71 as their disappearance was
not observable with a different dengue virus (DENV) as our control. Furthermore,
the Raman measurements from colloidal SERS were more sensitive in probing the
aggregation of AuNS-SCARB2 for detecting the presence of EV71 in protein-rich
samples compared to UV-vis spectrum measurements. With this facile "anti
aggregation" approach, we were able to detect EV71 in protein-rich biological
medium within 15 min with reasonable sensitivity of 107 pfu/mL and minimal sample
preparation, making this translatable for point-of-care applications.
PMID- 28414219
TI - Anion Encapsulation Drives the Formation of Dimeric GdIII[15-metallacrown-5]3+
Complexes in Aqueous Solution.
AB - Metallacrown complexes capable of sequestering dianions, as shown in the solid
state, also exist in aqueous solution at neutral pH, as demonstrated by
calorimetric and mass spectrometric data. The driving forces for the formation of
these dimeric complexes in solution strongly depend on the chain length of the
guest rather than its degree of unsaturation.
PMID- 28414220
TI - Alkane-Shape-Selective Vapochromic Behavior Based on Crystal-State Host-Guest
Complexation of Pillar[5]arene Containing One Benzoquinone Unit.
AB - Colored crystals of pillar[5]arene containing one benzoquinone unit were found to
exhibit alkane-shape-selective vapochromic behavior. Activated pillar[5]arene
crystals, prepared by removing solvated methanol from pillar[5]arene crystals,
changed color from dark-brown to light-red after exposure to linear alkane
vapors; however, no color changes were observed on exposure to branched or cyclic
alkanes. Uptake of methanol vapor by the activated crystals induced a different
color change, from dark-brown to black. This multi-vapochromism results from the
different intermolecular pi-stacking interactions between the benzoquinone and
1,4-diethoxybenzene units in the alkane- and methanol-containing crystals. Unlike
most known vapochromic materials, these pillar[5]arene-based materials were
highly stable; after uptake of n-alkanes or methanol the color of the crystals
did not change after storage in air for 3 weeks. This is because the included
guests were stabilized in the cavity by multiple CH/pi interactions.
PMID- 28414216
TI - Unraveling the Thousand Word Picture: An Introduction to Super-Resolution Data
Analysis.
AB - Super-resolution microscopy provides direct insight into fundamental biological
processes occurring at length scales smaller than light's diffraction limit. The
analysis of data at such scales has brought statistical and machine learning
methods into the mainstream. Here we provide a survey of data analysis methods
starting from an overview of basic statistical techniques underlying the analysis
of super-resolution and, more broadly, imaging data. We subsequently break down
the analysis of super-resolution data into four problems: the localization
problem, the counting problem, the linking problem, and what we've termed the
interpretation problem.
PMID- 28414221
TI - New Isolated-Pentagon-Rule Isomers of Fullerene C98 Captured as Chloro
Derivatives.
AB - Fullerene C98 possesses 259 isomers obeying the isolated pentagon rule (IPR),
from which two, nos. 116 and 248, have been confirmed earlier as chloro
derivatives. High-temperature chlorination of C98-containing mixtures afforded
crystals of several chloro derivatives, and their structure elucidation by X-ray
crystallography revealed the presence of new isomers, nos. 107, 109, and 120, in
the fullerene soot. Evidence for an isomer of no. 111 is also presented. In
addition, a new chloride of the known isomer 248 has been isolated and
structurally studied. The chlorination patterns of the chlorides are discussed in
terms of the formation of isolated C?C bonds and aromatic substructures on the
fullerene cages.
PMID- 28414222
TI - Supramolecular Photoactivatable Anticancer Hydrogels.
AB - A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA)
has been incorporated into G-quadruplex G4K+ borate hydrogels by using borate
ester linkages (Pt-G4K+B hydrogel). These were characterized by 11B NMR,
attenuated total reflection Fourier transform infrared spectroscopy, circular
dichroism, scanning electron microscopy and transmission electron microscopy.
Microscopy investigations revealed the transformation of an extended fiber
assembly into discrete flakes after incorporation of Pt-DA. Pt-DA showed
photocytotoxicity against cisplatin-resistant A2780Cis human ovarian cancer cells
(IC50 74 MUM, blue light) with a photocytotoxic index <2, whereas Pt-G4K+B
hydrogels exhibited more potent photocytotoxicity (IC50 3 MUM, blue light) with a
photocytotoxic index >5. Most notably, Pt-DA and Pt-G4K+B hydrogels show
selective phototoxicity for cancer cells versus normal fibroblast cells (MRC5).
PMID- 28414224
TI - Carbanion Translocations via Intramolecular Proton Transfers: A Quantum Chemical
Study.
AB - Intramolecular proton transfers are important processes in chemical reactions and
biological transformations. In particular, the translocation of reactive
carbanion centers can be achieved through 1,n-proton transfer in either a direct
or an assisted manner (via the protonation/deprotonation mechanism). Despite some
mechanistic investigations on proton transfers within zwitterionic species, no
guiding principles have been summarized for carbanion-induced intramolecular
proton transfers. Herein, we report our quantum chemical study on the carbanion
translocations via intramolecular proton transfers. Our calculations indicated
that the reaction barriers generally decrease with longer tether lengths and more
pi-withdrawing substituents. The physical bases behind these effects were
revealed according to the charge and bond energy decomposition analysis, showing
that the destabilizing closed-shell Pauli repulsions play important roles in
determining the relative ease of intramolecular proton transfers. We also found
that the thermodynamic driving force may affect the regiochemistry. This study
may help chemists to understand whether a carbanion translocation occurs via an
intramolecular proton transfer or with the assistance of proton shuttles, such as
water and alcohols.
PMID- 28414223
TI - Diversity-Oriented Stapling Yields Intrinsically Cell-Penetrant Inducers of
Autophagy.
AB - Autophagy is an essential pathway by which cellular and foreign material are
degraded and recycled in eukaryotic cells. Induction of autophagy is a promising
approach for treating diverse human diseases, including neurodegenerative
disorders and infectious diseases. Here, we report the use of a diversity
oriented stapling approach to produce autophagy-inducing peptides that are
intrinsically cell-penetrant. These peptides induce autophagy at micromolar
concentrations in vitro, have aggregate-clearing activity in a cellular model of
Huntington's disease, and induce autophagy in vivo. Unexpectedly, the solution
structure of the most potent stapled peptide, DD5-o, revealed an alpha-helical
conformation in methanol, stabilized by an unusual (i,i+3) staple which cross
links two d-amino acids. We also developed a novel assay for cell penetration
that reports exclusively on cytosolic access and used it to quantitatively
compare the cell penetration of DD5-o and other autophagy-inducing peptides.
These new, cell-penetrant autophagy inducers and their molecular details are
critical advances in the effort to understand and control autophagy. More
broadly, diversity-oriented stapling may provide a promising alternative to
polycationic sequences as a means for rendering peptides more cell-penetrant.
PMID- 28414225
TI - Reversible Gas-Solid Ammonia N-H Bond Activation Mediated by an Organopalladium
Complex.
AB - N-H bond activation of gaseous ammonia is achieved at room temperature in a
reversible solvent-free reaction using a solid dicyclopalladated azobenzene
complex. Monitoring of the gas-solid reaction in real-time by in situ solid-state
Raman spectroscopy enabled a detailed insight into the stepwise activation
pathway proceeding to the final amido complex via a stable diammine intermediate.
Gas-solid synthesis allowed for isolation and subsequent structural
characterization of the intermediate and the final amido product, which presents
the first dipalladated complex with the PdII-(MU-NH2)-PdII bridge. Gas-solid
reaction is readily followed via color changes associated with conformational
switching of the palladated azobenzene backbone. The reaction proceeds
analogously in solution and was characterized by UV-vis and NMR spectroscopies
showing the same stepwise route to the amido complex. Combining the experimental
data with density functional theory calculations we propose a stepwise mechanism
of this heterolytic N-H bond activation assisted by exogenous ammonia.
PMID- 28414227
TI - Quantifying the Role of Orbital Contraction in Chemical Bonding.
AB - This work reports an approach to variationally quantify orbital contraction in
chemical bonds by an extension of an energy decomposition analysis (EDA). The
orbital contraction energy is defined as the energy lowering due to optimization
of the isolated fragments (that combine to form the bond) with a specially
constructed virtual set of contraction/expansion functions. This set contains one
function per occupied orbital, obtained as the linear response to scaling the
nuclear charges. EDA results for a variety of single bonds show substantial
changes in the importance of orbital contraction; it plays a critical role for
bonds to H but only a very minor role in the bonds between heavier elements.
Additionally, energetic stabilization due to rehybridization is separated from
inductive polarization by the fact that no mixing with virtual orbitals is
involved and is shown to be significant in fragments such as NH2, OH, and F.
PMID- 28414226
TI - Testing the Push-Pull Hypothesis: Lewis Acid Augmented N2 Activation at Iron.
AB - We present a systematic investigation of the structural and electronic changes
that occur in an Fe(0)-N2 unit (Fe(depe)2(N2); depe = 1,2
bis(diethylphosphino)ethane) upon the addition of exogenous Lewis acids. Addition
of neutral boranes, alkali metal cations, and an Fe2+ complex increases the N-N
bond activation (Delta nuNN up to 172 cm-1), decreases the Fe(0)-N2 redox
potential, polarizes the N-N bond, and enables -N protonation at uncommonly
anodic potentials. These effects were rationalized using combined experimental
and theoretical studies.
PMID- 28414228
TI - Molecular Aspects of a Robust Assay for Ferroxidase Function of Ceruloplasmin.
AB - Ceruloplasmin (Cp) is one of the most complex multicopper oxidase enzymes and
plays an essential role in the metabolism of iron in mammals. Ferrous ion
supplied by the ferroportin exporter is converted by Cp to ferric ion that is
accepted by plasma metallo-chaperone transferrin. Study of the enzyme at the
atomic and molecular level has been hampered by the lack of a suitable ferrous
substrate. We have developed the classic chromophoric complex FeIIHx(Tar)2
(H2Tar, 4-(2-thiazolylazo)resorcinol; x = 0-2; overall charge omitted) as a
robust substrate for evaluation of the ferroxidase function of Cp and related
enzymes. The catalysis can be followed conveniently in real time by monitoring
the solution absorbance at 720 nm, a fingerprint of FeIIHx(Tar)2. The complex is
oxidized to its ferric form FeIIIHx(Tar)2 via the overall reaction sequence
FeIIHx(Tar)2 -> FeII-Cp -> FeIII-Cp -> FeIIIHx(Tar)2: i.e., Fe(II) is transferred
formally from FeIIHx(Tar)2 to the substrate docking/oxidation (SDO) site(s) in
Cp, followed by oxidation to product Fe(III) that is trapped again by the ligand.
Each Tar ligand in the above bis-complex coordinates the metal center in a
meridional tridentate mode involving a pH-sensitive -OH group (pKa > 12), and
this imposes rapid Fe(II) and Fe(III) transfer kinetics to facilitate the
catalytic process. The formation constants of both the ferrous and ferric
complexes at pH 7.0 were determined (log beta2' = 13.6 and 21.6, respectively),
as well as an average dissociation constant of the SDO site(s) in Cp (log KD' =
7.2).
PMID- 28414229
TI - Coding the Assembly of Polyoxotungstates with a Programmable Reaction System.
AB - Chemical transformations are normally conducted in batch or flow mode, thereby
allowing the chemistry to be temporally or spatially controlled, but these
approaches are not normally combined dynamically. However, the investigation of
the underlying chemistry masked by the self-assembly processes that often occur
in one-pot reactions and exploitation of the potential of complex chemical
systems requires control in both time and space. Additionally, maintaining the
intermediate constituents of a self-assembled system "off equilibrium" and
utilizing them dynamically at specific time intervals provide access to building
blocks that cannot coexist under one-pot conditions and ultimately to the
formation of new clusters. Herein, we implement the concept of a programmable
networked reaction system, allowing us to connect discrete "one-pot" reactions
that produce the building block{W11O38} = {W11} under different conditions and
control, in real time, the assembly of a series of polyoxometalate clusters
{W12O42} = {W12}, {W22O74} = {W22} 1a, {W34O116} = {W34} 2a, and {W36O120} =
{W36} 3a, using pH and ultraviolet-visible monitoring. The programmable networked
reaction system reveals that is possible to assemble a range of different
clusters using {W11}-based building blocks, demonstrating the relationship
between the clusters within the family of iso-polyoxotungstates, with the final
structural motif being entirely dependent on the building block libraries
generated in each separate reaction space within the network. In total, this
approach led to the isolation of five distinct inorganic clusters using a "fixed"
set of reagents and using a fully automated sequence code, rather than five
entirely different reaction protocols. As such, this approach allows us to
discover, record, and implement complex one-pot reaction syntheses in a more
general way, increasing the yield and reproducibility and potentially giving
access to nonspecialists.
PMID- 28414230
TI - Computer-Aided 13C NMR Chemical Profiling of Crude Natural Extracts without
Fractionation.
AB - A computer-aided, 13C NMR-based dereplication method is presented for the
chemical profiling of natural extracts without any fractionation. An algorithm
was developed in order to compare the 13C NMR chemical shifts obtained from a
single routine spectrum with a set of predicted NMR data stored in a natural
metabolite database. The algorithm evaluates the quality of the matching between
experimental and predicted data by calculating a score function and returns the
list of metabolites that are most likely to be present in the studied extract.
The proof of principle of the method is demonstrated on a crude alkaloid extract
obtained from the leaves of Peumus boldus, resulting in the identification of
eight alkaloids, including isocorydine, rogersine, boldine, reticuline,
coclaurine, laurotetanine, N-methylcoclaurine, and norisocorydine, as well as
three monoterpenes, namely, p-cymene, eucalyptol, and alpha-terpinene. The
results were compared to those obtained with other methods, either involving a
fractionation step before the chemical profiling process or using mass
spectrometry detection in the infusion mode or coupled to gas chromatography.
PMID- 28414231
TI - Organic Phosphorescence Nanowire Lasers.
AB - Organic solid-state lasers (OSSLs) based on singlet fluorescence have merited
intensive study as an important class of light sources. Although the use of
triplet phosphors has led to 100% internal quantum efficiency in organic light
emitting diodes (OLEDs), stumbling blocks in triplet lasing include generally
forbidden intersystem crossing (ISC) and a low quantum yield of phosphorescence
(PhiP). Here, we reported the first triplet-phosphorescence OSSL from a nanowire
microcavity of a sulfide-substituted difluoroboron compound. As compared with the
unsubstituted parent compound, the lone pair of electrons of sulfur substitution
plus the intramolecular charge transfer interaction introduced by the nitro
moiety lead to an highly efficient T1 (pi,pi*) <- S1 (n,pi*) ISC (PhiISC = 100%)
and a moderate PhiP (10%). This, plus the optical feedback provided by nanowire
Fabry-Perot microcavity, enables triplet-phosphorescence OSSL emission at 650 nm
under pulsed excitation. Our results open the door for a whole new class of laser
materials based on previously untapped triplet phosphors.
PMID- 28414232
TI - Application of Deep Eutectic Solvents (DES) for Phenolic Compounds Extraction:
Overview, Challenges, and Opportunities.
AB - The green chemistry era has pushed the scientific community to investigate and
implement new solvents in phenolic compounds (PC) extraction as alternatives to
organic solvents, which are toxic and may be dangerous. Recently, deep eutectic
solvents (DES) have been applied as extraction solvents for PC. They have the
advantages of biodegradability and ease of handling with very low toxicity.
Nevertheless, the extraction process is affected by several factors: affinity
between DES and the target compounds, the water content, the mole ratio between
DES' starting molecules, the liquid/solid ratio between the DES and sample, and
the conditions and extraction method. On the other hand, PC recovery from DES is
a challenge because they can establish a strong hydrogen bond network.
Alternatively, another possibility is to use DES as solvent extraction as well as
formulation medium. In this way, DES can be suitable for cosmetics,
pharmaceutical, or food applications.
PMID- 28414233
TI - Furfural: The Unimolecular Dissociative Photoionization Mechanism of the Simplest
Furanic Aldehyde.
AB - The unimolecular dissociation reactions of energy-selected furfural cations have
been studied by imaging photoelectron photoion coincidence spectroscopy at the
vacuum-ultraviolet (VUV) beamline of the Swiss Light Source. In the photon energy
range of 10.9-14.5 eV, furfural ions decay by numerous fragmentation channels.
Modeling the breakdown diagram yielded the 0 K appearance energies of 10.95 +/-
0.10, 11.16, and 12.03 eV for the c-C4H3O-CO+ (m/z = 95), c-C4H4O+ (m/z = 68),
and c-C3H3+ (m/z = 39) fragment ions, respectively, formed by parallel
dissociation channels. An internal conversion from the A" to the A' electronic
state via a conical intersection takes place along the reaction coordinate in the
case of the H-loss channel (c-C4H3O-CO+ formation). Quantum chemical calculations
and experimental results confirmed a fast conversion to the A' state and that the
rate-determining step is a tight transition state on the potential energy
surface. Appearance energies were also derived for the sequential dissociation
products from the furan cation, c-C4H4O+, for the formation of CH2CO+ (m/z = 42),
C3H4+ (m/z = 40), and CHO+ (m/z = 29) at 12.81, 12.80, and 13.34 eV,
respectively. Statistical rate theory modeling of the breakdown diagram can also
be used to predict the fractional ion abundances and thermal shifts in mass
spectrometric pyrolysis studies to help assigning the m/z channels either to
ionization of the neutrals or to dissociative ionization processes, with
potential use for combustion diagnostics. The cationic geometry optimizations
yielded functional-dependent spurious DFT minima and a deviating planar MP2
optimized geometry, which are briefly discussed.
PMID- 28414234
TI - Impact of Mutations at C-Terminus on Structures and Dynamics of Abeta40 and
Abeta42: A Molecular Simulation Study.
AB - Alzheimer's disease is presumed to be caused by the formation of intracellular
plaques of amyloid beta (Abeta) peptides inside neurons. The most abundant Abeta
forms are Abeta40 and Abeta42 comprising, respectively, 40 and 42 residues.
Recent experiments showed that the triple Gly33Val-Val36Pro-Gly38Val (VPV)
mutation causes Abeta42 to become "super-Abeta42" with elevated aggregation rates
and toxicity. Upon VPV mutation, oligomerization pathways of Abeta40 become
similar to those of the Abeta42 wild type. It was hypothesized that the super
behavior of Abeta42 occurs due to an enhanced content of the beta-turn and beta
hairpin, centered at residues 36-37, and the similarity in oligomerization
pathways of Abeta40-VPV and Abeta42-WT comes from the increased beta-turn
population. As this is based on simulation of the truncated fragments, this
hypothesis may not be valid for the full-length case, motivating us to perform
all-atom molecular dynamics simulations for full-length Abeta sequences. We
showed that the results obtained for truncated peptides fall short in explaining
the similarity of self-assembly pathways of Abeta40-VPV and Abeta42-WT. Instead,
we propose that the similarity is due to not only increased beta-turn population
but also due to the elevated beta-structure of the entire sequence. Similar to
VPV, the Gly33Val-Val36Asn-Gly38Leu mutation enhances the beta-structure and the
C-terminal beta-turn making the behavior of Abeta40 similar to that of Abeta42
WT.
PMID- 28414235
TI - Bis-Heteroleptic Ruthenium(II) Complex of Pendant Urea Functionalized Pyridyl
Triazole and Phenathroline for Recognition, Sensing, and Extraction of Oxyanions.
AB - A new bis-heteroleptic RuII complex based ditopic receptor, 1[PF6]2, having an
anion binding triazole -CH unit and appended 4-fluorophenyl urea arm has been
developed. 1H NMR and isothermal titration calorimetry (ITC) experiments showed
binding of 1[PF6]2 toward oxyanions such as phosphates (e.g., H2PO4- and HP2O73-)
and carboxylates (e.g., CH3CO2- and C6H5CO2-) anions selectively. 1H NMR studies
showed that highly basic phosphate anions such as HP2O73-/H2PO4- are bound by
both -CH and -NH units of complex 1[PF6]2. However, comparatively less basic
CH3CO2-, C6H5CO2- anions interacted with the urea -NH protons only. Thermodynamic
parameters obtained from ITC experiments suggested that binding of all the
interacting anions with complex 1[PF6]2 are highly enthalpy and entropy driven
processes. Importantly, complex 1[PF6]2 showed extraction of H2PO4-, CH3CO2-, and
C6H5CO2- anions from aqueous solution via liquid-liquid extraction with
efficiencies of 28%, 74%, and 80%, respectively. The influential role of the urea
moiety in the course of extraction is demonstrated by comparison with a model
complex, 2[PF6]2. Additionally, complex 1[PF6]2 is capable of selective sensing
of phosphate anions among all investigated anions.
PMID- 28414236
TI - Thermal Rearrangement of Sulfamoyl Azides: Reactivity and Mechanistic Study.
AB - The rearrangement of sulfamoyl azides under thermal conditions to form a C-C bond
while breaking two C-N bonds is reported. Mechanistic study shows that this
reaction goes through a Curtius-type rearrangement to form a 1,1-diazene, then
which rearranges possibly through both a concerted rearrangement process and a
stepwise radical process. This rearrangement could be used in the synthesis of
complex biologically active molecules, such as sterols, and piperine derivatives.
PMID- 28414237
TI - CuX-Activated N-Halosuccinimide: Synthesis of 3-Haloquinolines via Electrophilic
Cyclization of Alkynyl Imines.
AB - We report an electrophilic cyclization of alkynyl imines to afford
polysubstituted 3-haloquinolines using CuX-activated N-halosuccinimdes (NXS) as
electrophiles. Control experiments demonstrated that the NXS/CuX system might be
more active than single NXS and could be applied in the electrophilic cyclization
of electron- deficient substrates.
PMID- 28414238
TI - Template Approach to Crystalline GaN Nanosheets.
AB - Crystalline GaN nanosheets hold great challenge in growth and promising
application in optoelectronic nanodevices. In this work, we reported an
accessible template approach toward the rational synthesis of GaN nanosheets
through the nitridation of metastable gamma-Ga2O3 nanosheets synthesized from a
hydrothermal reaction. The cubic gamma-Ga2O3 nanosheets with smooth surface and
decent crystallinity can be directly converted into hexagonal GaN nanosheets with
similar morphology framework and comparable crystal quality in NH3 at 850
degrees C. UV-vis spectrum measurement reveals that the GaN nanosheets show a
band gap of 3.30 eV with strong visible absorption in the range of 370-500 nm.
The template synthetic strategy proposed in this work will open up more
opportunities for the achievement of a variety of sheetlike nanostructures that
can not be obtained through conventional routines and will undoubtedly further
promote the fundamental research of newly emerging sheetlike nanostructures and
nanotechnology.
PMID- 28414239
TI - A Novel Sample Preparation for Shotgun Proteomics Characterization of HCPs in
Antibodies.
AB - Residual host cell proteins (HCPs) in biopharmaceuticals derived from recombinant
DNA technology can present potential safety risks to patients or compromise
product stability. Thus, the downstream purification process is designed to
demonstrate robust removal of these impurities. ELISA using polyclonal anti-HCP
antibodies as reagents for capture, detection, and quantitation purposes is most
commonly used to monitor HCP removal during process development, but this
technique has limitations. More recently, LC-MS for residual HCP characterization
has emerged as a powerful tool to support purification process development.
However, mass spectrometry needs to overcome the enormous dynamic range to detect
low ppm levels of residual HCPs in biopharmaceutical samples. We describe a
simple and powerful methodology to characterize residual HCPs in (monoclonal)
antibodies by combining a novel sample preparation procedure using trypsin
digestion and a shotgun proteomics approach. Differing from the traditional
methodology, the sample preparation approach maintains nearly intact antibody
while HCPs are digested. Thus, the dynamic range for HCP detection by MS is 1 to
2 orders of magnitude less than the traditional trypsin digestion sample
preparation procedure. HCP spiking experiments demonstrated that our method could
detect 0.5 ppm of HCP with molecular weight >60 kDa, such as rPLBL2. Application
of our method to analyze a high-purity NIST monoclonal antibody standard RM 8670
derived from a murine cell line expression system resulted in detection of 60
mouse HCPs; twice as many as previously reported with 2D-UPLC/IM/MSE method. A
control monoclonal antibody used for 70 analyses over 450 days demonstrated that
our method is robust.
PMID- 28414240
TI - Light-Activated COS/H2S Donation from Photocaged Thiocarbamates.
AB - Hydrogen sulfide (H2S) is an important biomolecule, and responsive chemical tools
for its delivery are needed. Here, we utilize the photocleavable o-nitrobenzyl
group to unmask caged thiocarbamates and to access photoactivated H2S releasing
molecules. These donors function by the initial release of carbonyl sulfide
(COS), which is quickly hydrolyzed to H2S by carbonic anhydrase (CA). Our
investigations demonstrate that o-nitrobenzyl-caged thiocarbamates can serve as a
donor platform for the bio-orthogonal stimulated release of COS/H2S.
PMID- 28414241
TI - Hot Electron Transistor with van der Waals Base-Collector Heterojunction and High
Performance GaN Emitter.
AB - Single layer graphene is an ideal material for the base layer of hot electron
transistors (HETs) for potential terahertz (THz) applications. The ultrathin body
and exceptionally long mean free path maximizes the probability for ballistic
transport across the base of the HET. We demonstrate for the first time the
operation of a high-performance HET using a graphene/WSe2 van der Waals (vdW)
heterostructure as a base-collector barrier. The resulting device with a GaN/AlN
heterojunction as emitter, exhibits a current density of 50 A/cm2, direct current
gain above 3 and 75% injection efficiency, which are record values among graphene
base HETs. These results not only provide a scheme to overcome the limitations of
graphene-base HETs toward THz operation but are also the first demonstration of a
GaN/vdW heterostructure in HETs, revealing the potential for novel electronic and
optoelectronic applications.
PMID- 28414242
TI - Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1
yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5
carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical
Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis.
AB - Autotaxin is a circulating enzyme with a major role in the production of
lysophosphatic acid (LPA) species in blood. A role for the autotaxin/LPA axis has
been suggested in many disease areas including pulmonary fibrosis. Structural
modifications of the known autotaxin inhibitor lead compound 1, to attenuate hERG
inhibition, remove CYP3A4 time-dependent inhibition, and improve pharmacokinetic
properties, led to the identification of clinical candidate GLPG1690 (11).
Compound 11 was able to cause a sustained reduction of LPA levels in plasma in
vivo and was shown to be efficacious in a bleomycin-induced pulmonary fibrosis
model in mice and in reducing extracellular matrix deposition in the lung while
also reducing LPA 18:2 content in bronchoalveolar lavage fluid. Compound 11 is
currently being evaluated in an exploratory phase 2a study in idiopathic
pulmonary fibrosis patients.
PMID- 28414244
TI - Morphology Development in Solution-Processed Functional Organic Blend Films: An
In Situ Viewpoint.
AB - Solution-processed organic films are a facile route to high-speed, low cost,
large-area deposition of electrically functional components (transistors, solar
cells, emitters, etc.) that can enable a diversity of emerging technologies, from
Industry 4.0, to the Internet of things, to point-of-use heath care and elder
care. The extreme sensitivity of the functional performance of organic films to
structure and the general nonequilibrium nature of solution drying result in
extreme processing-performance correlations. In this Review, we highlight
insights into the fundamentals of solution-based film deposition afforded by
recent state-of-the-art in situ measurements of functional film drying. Emphasis
is placed on multimodal studies that combine surface-sensitive X-ray scattering
(GIWAXS or GISAXS) with optical characterization to clearly define the evolution
of solute structure (aggregation, crystallinity, and morphology) with film
thickness.
PMID- 28414243
TI - Synthesis of Chiral Tertiary Boronic Esters: Phosphonate-Directed Catalytic
Asymmetric Hydroboration of Trisubstituted Alkenes.
AB - Highly enantioselective rhodium-catalyzed hydroboration of allylic phosphonates
by pinacolborane affords chiral tertiary boronic esters. The beta-borylated
phosphonates are readily converted to chiral beta- and gamma-hydroxyphosphonates
and aminophosphonates and to phosphonates bearing a quaternary carbon
stereocenter. The utility of the latter is illustrated by the synthesis of (S)
(+)-bakuchiol methyl ether.
PMID- 28414245
TI - Interfacial Properties and Monolayer Collapse of Alkyl Benzenesulfonate
Surfactant Monolayers at the Decane-Water Interface from Molecular Dynamics
Simulations.
AB - The molecular structure of a surfactant molecule is known to have a great effect
on the interfacial properties and the type of nanostructures formed. In this
work, we have performed molecular dynamics simulations on six isomers of an alkyl
benzenesulfonate surfactant to investigate the effect of the degree and position
of aromatic substitution on the interfacial properties and on the collapse of the
surfactant monolayer at a decane-water interface. The surface pressure of the
monolayers was shown to increase with increasing surface coverage, until some of
the monolayers become mechanically unstable and form large undulations. Shifting
the primary alkyl chain of the surfactant from the para to the meta position was
found to significantly affect the orientation of the surfactant head groups,
while the attachment position of the benzene ring along the primary alkyl chain
plays a greater role in the orientation of the surfactant tails. In general, to
the extent considered in this work, our results suggest that additional alkyl
substitution and meta substitution of the primary alkyl chains increase both the
effectiveness and efficiency of the surfactants, and accelerate the onset of
monolayer collapse. The interface was found to consist of an inner Helmholtz
layer of partially dehydrated counterions in contact with the surfactant head
groups, an outer Helmholtz layer of hydrated counterions, and a diffuse layer.
The di- and trisubstituted surfactants formed nearly spherical swollen micelles
encapsulating pure decane, which effectively solubilizes decane in water as a
microemulsion. The monosubstituted surfactants formed elongated buds that
protrude from the interface, but did not detach from the monolayer. To our
knowledge, the role of aromatic substitution on interfacial properties has not
been investigated by molecular simulations previously. The results from this work
could provide insights to design improved surfactants by exploiting aromatic
substitution to encapsulate material for drug delivery and other applications.
PMID- 28414246
TI - Ganoderin A, a novel 9,11-secosterol from Ganoderma lucidum spores oil.
AB - In this study, four sterols were isolated from the Ganoderma lucidum spores oil
obtained via supercritical CO2 extraction. Four chemical constituents were
ganoderin A (1), chaxine B (2), ergosterol, (3) and stellasterol (4). All the
separated ingredients were characterized using spectral data interpretation and
by comparing with reported data. Noticeably, stellasterol and chaxine B were both
firstly isolated from Ganoderma lucidum spores oil and ganoderin A was shown to
bear an unprecedented skeleton.
PMID- 28414247
TI - Preoperative sexual status of Japanese localized prostate cancer patients:
comparison of sexual activity and EPIC scores.
AB - OBJECTIVE: This study aimed to evaluate the relationship between sexual activity
and sexual function using questionnaires distributed to middle-aged Japanese
patients with localized prostate cancer. METHODS: A total of 145 patients who
underwent radical prostatectomy were enrolled in the survey reported on herein.
Sexual activity and sexual function were investigated via the Expanded Prostate
Cancer Index Composite (EPIC) and an original self-reported questionnaire.
RESULTS: Of participants, 24.1% and 20.7% had sexual activity within a month
period as investigated via the EPIC and original questionnaire, respectively.
However, 29.7% of all those who reported sexual activity rate reported "about
once every 2 months to a year," as shown in the original questionnaire. Regarding
sexual function as addressed through EPIC, no results within that questionnaire's
measure of sexual function showed significant differences among patients with a
rate of actual sexual activity. CONCLUSIONS: The present survey showed that more
than quarter of preoperative middle-aged Japanese prostate cancer patients
surveyed had actual sexual activity, though not within the preceding 4 weeks. To
precisely evaluate sexual function of middle-aged Japanese patients, it is
necessary to consider actual sexual activity.
PMID- 28414248
TI - Factors that predict discharge recommendations following paediatric mild
traumatic brain injury.
AB - PRIMARY OBJECTIVE: To investigate factors that predict discharge recommendations
for children and adolescents who present to an Australian paediatric Emergency
Department (ED) following a mild traumatic brain injury (mTBI). RESEARCH DESIGN:
Retrospective data base analysis. METHODS: The study retrospectively analysed an
ED database to test the relationship between injury risk factors (symptoms,
Glasgow Coma Scale, prior TBI, mechanism of injury and Computed Tomography scan),
non-injury risk factors (sex, age, socio-economic status (SES)) and discharge
recommendations of 2807 children and adolescents (0-18 years) who presented to a
children's hospital ED over a three year period with mTBI. RESULTS: Univariate
analyses indicated a statistically significant association of discharge
recommendations with age, SES, mechanism of injury and vomiting. However,
multivariate analyses indicated vomiting and mechanism of injury were the only
statistically significant risk factor associated with discharge recommendations,
when controlling for other risk factors. CONCLUSIONS: The current study suggests
vomiting and mechanism of injury are the only risk factors predicting discharge
recommendations for children and adolescents with mTBI.
PMID- 28414249
TI - Psychological distress is associated with altered cognitive functioning in family
caregivers of patients with disorders of consciousness.
AB - OBJECTIVES: To analyse the possible presence of reduced cognitive efficiency in
family caregivers of patients with prolonged disorders of consciousness (DOC).
SUBJECTS: The participants were 27 caregivers of 25 patients with DOC admitted to
the severe brain injury units of the ICS Maugeri, Institutes of Telese Terme and
Sciacca, Italy. METHODS: We examined cognitive functions such as short- and long
term memory, executive functions and attention by means of standardized tests. We
also assessed features of psychological distress such as anxiety, depression,
psychophysiological symptoms, prolonged grief disorder, psychological burden and
quality of life. All scores on neuropsychological tests were compared with those
of the 15 matched control subjects. RESULTS: Enrolled family caregivers showed
high frequency of clinically relevant depressive symptoms and anxiety; half of
them met the criteria for prolonged grief disorder. Caregivers achieved scores
lower than the matched controls on tests for selective attention, verbal fluency
and long-term spatial memory. CONCLUSIONS: Family caregivers' burden is
associated with a reduced efficiency of selected executive measures and
visuospatial learning. These results emphasize the need for appropriate
psychological and cognitive supporting therapies for family caregivers of
patients with DOC, also considering their delicate involvement in clinical
decision-making and in providing care.
PMID- 28414250
TI - Longitudinal changes in brain morphology from 4 weeks to 12 months after mild
traumatic brain injury: Associations with cognitive functions and clinical
variables.
AB - OBJECTIVE: To investigate longitudinal changes in cortical and subcortical
volumes in patients with mild traumatic brain injury (MTBI) and to evaluate
whether such changes were associated with self-reported post-concussive symptoms,
global functional outcomes and neuropsychological functioning. METHODS: This was
a prospecitve, longitudinal cohort study of patients with complicated (i.e
presence of intracranial abnormalities on the day of injury CT) and uncomplicated
MTBI (i.e, absence of intracranial abnormalities). Magnetic resonance imaging
(MRI) was performed at approximately 4 weeks and 12 months. We utilized a 3T MRI
system, cortical reconstruction and volumetric segmentation by FreeSurfer
software. We included 33 patients with uncomplicated and 29 with complicated
MTBI, who were aged 16-65 years. RESULTS: 12 months after MTBI, significant
within-group volume reductions were detected in the left accumbens area and right
caudate nucleus for both patients groups, but no significant differences between
the groups were revealed. No associations between volumetric variables and post
concussive symptoms or global functioning were found. The left temporal thickness
was significantly associated with executive functioning. CONCLUSION: Structural
subcortical alterations occur after complicated and uncomplicated MTBIs but these
findings were not associated with symptoms burden or functional outcomes.
Nonetheless, worse executive functioning was found in patients with shrinkage of
the left temporal lobe.
PMID- 28414251
TI - Impact of metabolic status on the association of serum vitamin D with
hypogonadism and lower urinary tract symptoms/benign prostatic hyperplasia.
AB - OBJECTIVE: The objective of this study is to investigate the impact of metabolic
status on associations of serum vitamin D with hypogonadism and lower urinary
tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A
total of 612 men underwent physical examination, biochemical/hormonal blood
testing, and transrectal prostate ultrasound. Moreover, the subjects filled out
standard questionnaires for identification and grading of LUTS and hypogonadism
symptoms. Parameters were statistically compared with independent t-tests and
correlation analyses. RESULTS: Vitamin D levels positively correlated with total
testosterone (TT) but not with prostate volume or International Prostate Symptom
Score (IPSS). Patients with metabolic syndrome had significantly lower vitamin D
levels, which were not correlated with TT, prostate volume, or IPSS. However,
vitamin D was positively correlated with TT, and negatively correlated with
prostate volume and quality-of-life IPSS in subjects without metabolic syndrome.
CONCLUSION: The clinical usefulness of vitamin D for treatment of hypogonadism or
LUTS/BPH varies according to metabolic status.
PMID- 28414252
TI - Environmental impacts of genetically modified (GM) crop use 1996-2015: Impacts on
pesticide use and carbon emissions.
AB - This paper updates previous assessments of important environmental impacts
associated with using crop biotechnology in global agriculture. It focuses on the
environmental impacts associated with changes in pesticide use and greenhouse gas
emissions arising from the use of GM crops since their first widespread
commercial use in the mid-1990s. The adoption of GM insect resistant and
herbicide tolerant technology has reduced pesticide spraying by 618.7 million kg
(-8.1%) and, as a result, decreased the environmental impact associated with
herbicide and insecticide use on these crops (as measured by the indicator, the
Environmental Impact Quotient (EIQ)) by18.6%. The technology has also facilitated
important cuts in fuel use and tillage changes, resulting in a significant
reduction in the release of greenhouse gas emissions from the GM cropping area.
In 2015, this was equivalent to removing 11.9 million cars from the roads.
PMID- 28414253
TI - Suggestions for assessment of muscle mass in primary care setting.
AB - Sarcopenia is one of the prevalent geriatric syndromes that adversely affects the
functionality in the older adults. The diagnosis of sarcopenia requires
documentation of decreased muscle mass and decreased muscle strength or physical
function. The implication of user-friendly and inexpensive methods that could be
used to assess sarcopenia in real-life settings is suggested in a recent debate
paper. For muscle mass assessment, bioelectric impedance analysis (BIA), and dual
energy X-ray absorptiometry (DXA) were described as having the same ease for
muscle mass assessment in terms of applicability. However, BIA is easier to
perform, has greater availability, inexpensive, and does not require specialist
trained staff. The authors proposed the use of DXA as primary tool to assess
muscle mass in the primary care setting. However, BIA is recommended as a first
line method both in research and clinical practice by EWGSOP. Regarding its much
easier applicability, we conclude that BIA is a more practical method for muscle
mass assessment in the primary care setting than the DXA. Thus, we suggest that
BIA could be the method of choice for muscle mass assessment in the primary care
setting.
PMID- 28414254
TI - Lifestyle intervention for adults with spinal cord injury: Results of the USC
RLANRC Pressure Ulcer Prevention Study.
AB - CONTEXT/OBJECTIVE: Medically serious pressure injuries (MSPrIs), a common
complication of spinal cord injury (SCI), have devastating consequences on health
and well-being and are extremely expensive to treat. We aimed to test the
efficacy of a lifestyle-based intervention designed to reduce incidence of MSPrIs
in adults with SCI. DESIGN: A randomized controlled trial (RCT), and a separate
study wing involving a nonrandomized standard care control group. SETTING: Rancho
Los Amigos National Rehabilitation Center, a large facility serving ethnically
diverse, low income residents of Los Angeles County. PARTICIPANTS: Adults with
SCI, with history of one or more MSPrIs over the past 5 years: N=166 for RCT
component, N=66 in nonrandomized control group. INTERVENTIONS: The Pressure Ulcer
Prevention Program, a 12-month lifestyle-based treatment administered by
healthcare professionals, largely via in-home visits and phone contacts. OUTCOME
MEASURES: Blinded assessments of annualized MSPrI incidence rates at 12 and 24
months, based on: skin checks, quarterly phone interviews with participants, and
review of medical charts and billing records. Secondary outcomes included number
of surgeries and various quality-of-life measures. RESULTS: Annualized MSPrI
rates did not differ significantly between study groups. At 12 months, rates were
.56 for intervention recipients, .48 for randomized controls, and .65 for
nonrandomized controls. At follow-up, rates were .44 and .39 respectively for
randomized intervention and control participants. CONCLUSIONS: Evidence for
intervention efficacy was inconclusive. The intractable nature of MSPrI threat in
high-risk SCI populations, and lack of statistical power, may have contributed to
this inability to detect an effect. TRIAL REGISTRATION: ClinicalTrials.gov
NCT01999816.
PMID- 28414255
TI - A Quantitative Assessment of the Risk of Human Salmonellosis Arising from the
Consumption of Almonds in the United States: The Impact of Preventive Treatment
Levels.
AB - The presence of Salmonella on almonds continues to result in product-related
outbreaks and recalls in the United States. In this study, the impact of
microbial reduction treatment levels (1 to 5 log CFU) on the risk of human
salmonellosis from the consumption of almond kernels in the United States was
evaluated. An exposure model, including major steps in almond processing, was
used to estimate prevalence and levels of contamination of Salmonella on almonds
at the point of consumption. A Salmonella dose-response model and consumption
data for almonds in the United States were used to assess risk of illness per
serving and per year, quantifying variability and uncertainty separately. A 3-log
reduction treatment resulted in a predicted mean risk of illness of two cases per
year for almonds consumed as a core product not cooked at home (95% confidence
interval [CI], one to four cases), one case per year for almonds consumed as an
ingredient not cooked at home (95% CI, one to two cases), and less than one case
per year for almonds consumed as an ingredient cooked at home (95% CI, 7 * 10-7
to 3 * 10-6 cases). A minimum 4-log reduction treatment resulted in an estimated
mean risk of illness below one case per year in the United States. This study
also includes an assessment of the risk of human salmonellosis as a result of an
exceptional situation, which results in higher risk estimates compared with the
baseline model. The exceptional situations modeled posttreatment resulted in
estimates of mean risk that were not significantly affected by treatment level.
Sensitivity analysis results showed initial Salmonella contamination level to be
the factor with the most impact on risk per serving estimates, given a certain
treatment level. The risk assessment also includes a simulation of the events
that occurred in 2001. Treatment levels with a minimum 4-log microbial reduction
would have been sufficient to prevent the outbreak cases. The uncertainty range
in the estimates indicates that additional information is needed to make more
precise predictions of this specific outbreak event.
PMID- 28414256
TI - Salmonella Survival Kinetics on Pecans, Hazelnuts, and Pine Nuts at Various Water
Activities and Temperatures.
AB - The impact of temperature, water activity (aw), and nut composition on Salmonella
survival on tree nuts has not been thoroughly examined. The aim of this study was
to determine the effect of temperature, aw, and nut composition on the survival
of Salmonella on tree nuts and develop predictive models. Pecans, hazelnuts, and
pine nuts were chosen based on differences in their typical fat content. Nuts
were inoculated with a cocktail of five Salmonella serotypes (11 log CFU/mL) and
then were dried and stored at 4, 10, and 25 degrees C at 0.41 +/- 0.06 and 0.60
+/- 0.05 aw for 1 year. Ten-gram quantities were removed at different intervals
up to 364 days to test for surviving Salmonella populations (plating on selective
and nonselective media) and aw. Experiments were carried out in triplicate.
Salmonella populations were relatively stable over a year at 4 and 10 degrees C
at both aw levels with <1.5-log CFU/g decline. The best predictive model to
describe Salmonella survival at 4 and 10 degrees C was a log-linear model with a
D-value for each tree nut and aw combination. Significant declines in Salmonella
levels were observed at 25 degrees C, where the best fit was a Weibull model with
a fixed rho for all tree nuts (rho = 0.86), a delta value for each tree nut and
aw combination, and a random factor to account for variability among replicates.
The time for the first log reduction at 25 degrees C and 0.37 +/- 0.009 aw was
estimated at 24 +/- 2 weeks for hazelnuts, 34 +/- 3 weeks for pecans, and 52 +/-
7 weeks for pine nuts. At the same temperature, but with 0.54 +/- 0.009 aw, the
mean estimated time for the first log reduction decreased to 9 +/- 1 weeks for
hazelnuts, 10 +/- 1 weeks for pecans, and 16 +/- 1 weeks for pine nuts. Tree nut,
aw, and temperature were shown to have a statistically significant effect on
survival ( P < 0.05). No apparent influence of fat content on survival was
observed. The results of this study can be used to predict changes in Salmonella
levels on pecans, hazelnuts, and pine nuts after storage at the different
temperatures and aw values.
PMID- 28414257
TI - Spiral Plating Method To Quantify the Six Major Non-O157 Escherichia coli
Serogroups in Cattle Feces.
AB - Cattle are a major reservoir of the six major Shiga toxin-producing non-O157
Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, and O145)
responsible for foodborne illnesses in humans. Besides prevalence in feces, the
concentrations of STEC in cattle feces play a major role in their transmission
dynamics. A subset of cattle, referred to as super shedders, shed E. coli O157 at
high concentrations (>=4 log CFU/g of feces). It is not known whether a similar
pattern of fecal shedding exists for non-O157. Our objectives were to initially
validate the spiral plating method to quantify the six non-O157 E. coli
serogroups with pure cultures and culture-spiked fecal samples and then determine
the applicability of the method and compare it with multiplex quantitative PCR
(mqPCR) assays for the quantification of the six non-O157 E. coli serogroups in
cattle fecal samples collected from commercial feedlots. Quantification limits of
the spiral plating method were 3 log, 3 to 4 log, and 3 to 5 log CFU/mL or CFU/g
for individual cultures, pooled pure cultures, and cattle fecal samples spiked
with pooled pure cultures, respectively. Of the 1,152 cattle fecal samples tested
from eight commercial feedlots, 122 (10.6%) and 320 (27.8%) harbored
concentrations >=4 log CFU/g of one or more of the six serogroups of non-O157 by
spiral plating and mqPCR methods, respectively. A majority of quantifiable
samples, detected by either spiral plating (135 of 137, 98.5%) or mqPCR (239 of
320, 74.7%), were shedding only one serogroup. Only one of the quantifiable
samples was positive for a serogroup carrying Shiga toxin (stx1) and intimin
(eae) genes; 38 samples were positive for serogroups carrying the intimin gene.
In conclusion, the spiral plating method can be used to quantify non-O157
serogroups in cattle feces, and our study identified a subset of cattle that was
super shedders of non-O157 E. coli . The method has the advantage of quantifying
non-O157 STEC, unlike mqPCR that quantifies serogroups only.
PMID- 28414258
TI - Postchill Antimicrobial Treatments To Control Salmonella, Listeria, and
Campylobacter Contamination on Chicken Skin Used in Ground Chicken.
AB - Ground poultry products are frequently contaminated with foodborne pathogens.
With the potential for increased regulatory scrutiny, it is important to use
sufficient intervention strategies to control pathogen levels effectively. A
large proportion of the bacteria introduced to ground chicken are likely to come
from broiler skin, which is added to achieve target fat content and maintain
product texture and taste. In this research, antimicrobials, including 50 ppm of
chlorine and 1,200 ppm of peracetic acid (PAA), were applied in a postchill
system to reduce the number of Salmonella Typhimurium, Listeria monocytogenes ,
and Campylobacter coli inoculated on chicken skin used to formulate ground
chicken. Results showed that chlorine provided no significant effect in reducing
the number of pathogens in ground chicken made with treated skin compared with
water treatment but that it did help decrease pathogens in postchill water. PAA
was found to be an effective (P <= 0.05) antimicrobial agent, not only in
reducing the number of pathogens on ground chicken, but also in postchill water.
Treating chicken skin with PAA prior to inclusion in ground chicken can be an
effective intervention strategy to lessen contamination in a ground chicken meat
product.
PMID- 28414259
TI - Mixed-effects location and scale Tobit joint models for heterogeneous
longitudinal data with skewness, detection limits, and measurement errors.
AB - The joint modeling of mean and variance for longitudinal data is an active
research area. This type of model has the advantage of accounting for
heteroscedasticity commonly observed in between and within subject variations.
Most of researches focus on improving the estimating efficiency but ignore many
data features frequently encountered in practice. In this article, we develop a
mixed-effects location scale joint model that concurrently accounts for
longitudinal data with multiple features. Specifically, our joint model handles
heterogeneity, skewness, limit of detection, measurement errors in covariates
which are typically observed in the collection of longitudinal data from many
studies. We employ a Bayesian approach for making inference on the joint model.
The proposed model and method are applied to an AIDS study. Simulation studies
are performed to assess the performance of the proposed method. Alternative
models under different conditions are compared.
PMID- 28414260
TI - Retention in HIV Care and Viral Suppression: Individual- and Neighborhood-Level
Predictors of Racial/Ethnic Differences, Florida, 2015.
AB - The objective of this study was to estimate racial/ethnic differences in
retention in HIV care and viral suppression and to identify related individual
and neighborhood determinants. Florida HIV surveillance records of cases aged
>=13 years diagnosed during the years 2000-2014 were analyzed. Retention in care
was defined as evidence of >=2 or more laboratory tests, receipts of
prescription, or clinical visits at least 3 months apart during 2015. Viral load
suppression was defined as a viral load of <200 copies/mL for the last test in
2015. Multi-level logistic regressions were used to estimate adjusted odds ratios
(AORs). Of 65,735 cases, 33.3% were not retained in care, and 40.1% were not
virally suppressed. After controlling for individual and neighborhood factors,
blacks were at increased odds of nonretention in HIV care [AOR 1.29, 95%
confidence interval (CI) 1.23-1.35] and nonviral suppression (AOR 1.55, 95% CI
1.48-1.63) compared with whites. Black and Latino males compared with their
female counterparts had higher odds of nonretention and nonviral suppression.
Compared with their US-born counterparts, foreign-born blacks and whites, but not
Latinos, had higher odds of nonretention and nonviral suppression. Blacks and
whites in urban compared with rural areas had higher odds of both outcomes.
Disparities in retention in care and viral suppression persist and are not
accounted for by differences in age, sex, transmission mode, AIDS diagnosis,
neighborhood socioeconomic status, rural/urban residence, or neighborhood racial
composition. Further, predictors of poor retention in care and viral suppression
appear to differ by race/ethnicity.
PMID- 28414261
TI - "Support Your Client at the Space That They're in": HIV Pre-Exposure Prophylaxis
(PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation.
AB - Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and
evidence that most PrEP users do not engage in risk compensation (i.e., increased
risk behavior due to a perceived decrease in HIV susceptibility), some healthcare
providers report patient risk compensation to be a deterrent to prescribing PrEP.
Overcoming this barrier is essential to supporting PrEP access and uptake among
people at risk for HIV. To inform such efforts, this qualitative study explored
PrEP-related risk compensation attitudes among providers with firsthand
experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were
HIV specialists, were recruited through direct outreach and referral from
colleagues and other participants. Individual 90-min semistructured interviews
were conducted by phone or in person from September 2014 through February 2015,
transcribed, and thematically analyzed. Three attitudinal themes emerged: (1)
providers' role is to support patients in making informed decisions, (2) risk
behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e.,
PrEP confers net protection, even with added behavioral risk), and (3) PrEP
related risk compensation is unduly stigmatized within and beyond the healthcare
community. Participants were critical of other healthcare providers' negative
judgment of patients and reluctance to prescribe PrEP due to anticipated risk
compensation. Several providers also acknowledged an evolution in their thinking
from initial ambivalence toward greater acceptance of PrEP and PrEP-related
behavior change. PrEP providers' insights about risk compensation may help to
address unsubstantiated concerns about PrEP-related risk compensation and
challenge the acceptability of withholding PrEP on these grounds.
PMID- 28414262
TI - Mitey Costly: Energetic Costs of Parasite Avoidance and Infection.
AB - Parasites reduce host fitness via perturbations to host energy allocation,
growth, survival, and reproduction. Here, we investigate the independent effects
of parasite exposure and infection on host metabolic rate. Our study focuses on
Drosophila hydei and a naturally occurring ectoparasitic mite, Macrocheles
muscaedomesticae. We use flow-through respirometry to measure the metabolic rate
of flies during the period of exposure (preinfection) and during mite attachment.
Flies were exposed to mites either indirectly (through a mesh screen) or
directly, allowing for physical contact between the fly and the mite. We
predicted that fly metabolic rate would increase with the level of parasite
exposure: unexposed flies < flies with indirect exposure to mites < flies with
direct contact with mites < flies actively infected with mites. As expected,
flies indirectly exposed to but not in direct contact with mites produced 70%
more CO2 than unexposed flies. Flies in direct contact with mites produced 35%
more CO2 than flies with indirect contact, and this was more than double the
amount of CO2 produced by unexposed flies. However, infected flies-those actually
carrying mites-did not produce significantly more CO2 than uninfected flies. Our
results show that simply being exposed to mites, either indirectly or directly,
was sufficient to elicit a response from the host in terms of elevated CO2
production. Our results show that the costs of parasitism can potentially extend
beyond the physiological costs of infection per se to include the energetic costs
associated with parasite avoidance. Although studies have shown energetic costs
associate with predator-avoidance behaviors, no study to our knowledge has
measured the metabolic cost of parasite avoidance.
PMID- 28414263
TI - Effective enhancement of polylactic acid-degrading enzyme production by
Amycolatopsis sp. strain SCM_MK2-4 using statistical and one-factor-at-a-time
approaches.
AB - This study aims to find the optimal medium and conditions for polylactic acid
(PLA)-degrading enzyme production by Amycolatopsis sp. SCM_MK2-4. Screening of
the most effective components in the enzyme production medium by Plackett-Burman
design revealed that the silk cocoon and PLA film were the most significant
variables enhancing the PLA-degrading enzyme production. After an response
surface methodology, a maximum amount of PLA-degrading enzyme activity at 0.74 U
mL-1 was predicted and successfully validated at 95% after 0.39% (w/v) silk
cocoon and 1.62% (w/v) PLA film were applied to the basal medium. The optimal
initial pH value, temperature, and inoculum size were evaluated by a method
considering one-factor-at-a-time. The values were recorded at an initial pH in
the range of 7.5-9.0, a temperature of 30-32 degrees C, and an inoculum size of 4
10%. The highest activity of approximately 0.95 U mL-1 was achieved after 4 days
of cultivation using the optimized medium and under optimized conditions in a
shake flask. Upscaling to the use of a 3-L stirred tank fermenter was found to be
successful with a PLA-degrading activity of 5.53 U mL-1; which represents a 51
fold increase in the activity compared with that obtained from the nonoptimized
medium and conditions in the shake flask.
PMID- 28414264
TI - The rice transcription factors OsICE confer enhanced cold tolerance in transgenic
Arabidopsis.
AB - Cold stress is one of the major constraints for crop yield. Plants have in turn
evolved highly sophisticated mechanisms involving altered physiologic and
biochemical processes to cope with the cold stress. Previous studies have
revealed that the INDUCER OF CBF EXPRESSION 1 (ICE1), a basic helix-loop-helix
(bHLH) transcription factor, directly binds and activates the expression of C
Repeat Binding Factor/Dehydration-Responsive-Element-Binding protein (CBF/DREB1)
to regulate the cold-response pathway in Arabidopsis thaliana. However, the
function of AtICE1 orthologues in rice is largely unknown. Here we identified
that OsICE1 and OsICE2 in rice shared highly conserved amino acid sequence with
AtICE1 in Arabidopsis. Overexpression of OsICE1 and OsICE2 in Arabidopsis
significantly enhanced the cold tolerance of Arabidopsis seedlings and improved
the expression of cold-response genes. Furthermore, we showed that both OsICE1
and OsICE2 physically interact with OsMYBS3, a single DNA-binding repeat MYB
transcription factor that is essential for cold adaptation in rice, suggesting
that OsICE1/OsICE2 and OsMYBS3 probably act through specific signal transduction
mechanisms to coordinate cold tolerance in rice. These results demonstrated that
the 2 OsICEs are orthologues of AtICE1 and play positive regulators in activation
of cold-response genes to regulate the cold tolerance.
PMID- 28414265
TI - Effectiveness of a Home-Based Eccentric-Exercise Program on the Torque-Angle
Relationship of the Shoulder External Rotators: A Pilot Study.
AB - CONTEXT: The role of the rotator cuff is to provide dynamic stability to the
glenohumeral joint. Human and animal studies have identified sarcomerogenesis as
an outcome of eccentric training indicated by more torque generation with the
muscle in a lengthened position. OBJECTIVE: The authors hypothesized that a home
based eccentric-exercise program could increase the shoulder external rotators'
eccentric strength at terminal internal rotation (IR). DESIGN: Prospective case
series. SETTING: Clinical laboratory and home exercising. PARTICIPANTS: 10
healthy subjects (age 30 +/- 10 y). INTERVENTION: All participants performed 2
eccentric exercises targeting the posterior shoulder for 6 wk using a home-based
intervention program using side-lying external rotation (ER) and horizontal
abduction. MAIN OUTCOME MEASURES: Dynamic eccentric shoulder strength measured at
60 degrees /s through a 100 degrees arc divided into 4 equal 25 degrees arcs
(ER 50-25 degrees , ER 25-0 degrees , IR 0-25 degrees , IR 25-50 degrees ) to
measure angular impulse to represent the work performed. In addition, isometric
shoulder ER was measured at 5 points throughout the arc of motion (45 degrees
IR, 30 degrees IR, 15 degrees IR, 0 degrees , and 15 degrees ER). Comparison
of isometric and dynamic strength from pre- to posttesting was evaluated with a
repeated-measure ANOVA using time and arc or positions as within factors.
RESULTS: The isometric force measures revealed no significant differences between
the 5 positions (P = .56). Analysis of the dynamic eccentric data revealed a
significant difference between arcs (P = .02). The percentage-change score of the
arc of IR 25-50 degrees was found to be significantly greater than that of the
arc of IR 0-25 degrees (P = .007). CONCLUSION: After eccentric training the only
arc of motion that had a positive improvement in the capacity to absorb eccentric
loads was the arc of motion that represented eccentric contractions at the
longest muscle length.
PMID- 28414266
TI - Eccentric Contractions: They Are Not So "Odd" Anymore.
PMID- 28414267
TI - Withdrawal: Rigby and Draper (2017).
AB - We, the Authors, Editors and Publishers of Journal of Sport Rehabilitation, have
withdrawn the following article in whole:Rigby, JH, Draper, DO. Effects of long
duration low intensity ultrasound for active trapezius trigger points: a
randomized clinical trial [version of record published online ahead of print
February 9, 2017]. J Sport Rehabil. doi: 10.1123/jsr.2016-0150.The Editorial
Office was contacted by the author with the request to withdraw this article,
while informing the Editor-in-Chief that the manufacturer of a device used in
this study had contacted the author to disclose that the data reported in the
manuscript had possibly been affected by the failure of the device.
PMID- 28414268
TI - Shifting the Current Clinical Perspective: Isolated Eccentric Exercise as an
Effective Intervention to Promote the Recovery of Muscle After Injury.
AB - Eccentric exercise is able to mechanically engage muscle, initiating strain
sensing molecules that promote muscle recovery by inducing beneficial adaptations
in neural activity and muscle morphology, 2 critical components of muscle
function that are negatively altered after injury. However, due to misinterpreted
mathematic modeling and in situ and in vitro stretch protocols, a dogma that
exposing muscle to eccentric exercise is associated with injury has been
perpetuated in the literature. In response, clinicians have been biased toward
using concentric exercise postinjury to improve the recovery of muscle function.
Unfortunately, this conventional approach to rehabilitation does not restore
muscle function, and reinjury rates remain high. Here, the authors present
experimental evidence and theoretical support for the idea that isolated
eccentric exercise is ideally suited to combat muscle inhibition and muscle
strains and is an attractive alternative to concentric exercise.
PMID- 28414269
TI - Continuous transport of a small fraction of plasma membrane cholesterol to
endoplasmic reticulum regulates total cellular cholesterol.
AB - Cells employ regulated transport mechanisms to ensure that their plasma membranes
(PMs) are optimally supplied with cholesterol derived from uptake of low-density
lipoproteins (LDL) and synthesis. To date, all inhibitors of cholesterol
transport block steps in lysosomes, limiting our understanding of post-lysosomal
transport steps. Here, we establish the cholesterol-binding domain 4 of
anthrolysin O (ALOD4) as a reversible inhibitor of cholesterol transport from PM
to endoplasmic reticulum (ER). Using ALOD4, we: (1) deplete ER cholesterol
without altering PM or overall cellular cholesterol levels; (2) demonstrate that
LDL-derived cholesterol travels from lysosomes first to PM to meet cholesterol
needs, and subsequently from PM to regulatory domains of ER to suppress
activation of SREBPs, halting cholesterol uptake and synthesis; and (3) determine
that continuous PM-to-ER cholesterol transport allows ER to constantly monitor PM
cholesterol levels, and respond rapidly to small declines in cellular cholesterol
by activating SREBPs, increasing cholesterol uptake and synthesis.
PMID- 28414271
TI - Monitoring ATP dynamics in electrically active white matter tracts.
AB - In several neurodegenerative diseases and myelin disorders, the degeneration
profiles of myelinated axons are compatible with underlying energy deficits.
However, it is presently impossible to measure selectively axonal ATP levels in
the electrically active nervous system. We combined transgenic expression of an
ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological
recordings of acutely isolated optic nerves. This allowed us to monitor dynamic
changes and activity-dependent axonal ATP homeostasis at the cellular level and
in real time. We find that changes in ATP levels correlate well with compound
action potentials. However, this correlation is disrupted when metabolism of
lactate is inhibited, suggesting that axonal glycolysis products are not
sufficient to maintain mitochondrial energy metabolism of electrically active
axons. The combined monitoring of cellular ATP and electrical activity is a novel
tool to study neuronal and glial energy metabolism in normal physiology and in
models of neurodegenerative disorders.
PMID- 28414270
TI - Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body
adipose hyperplasia, and suppression of leptin expression.
AB - MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane
fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy,
with associated lipodystrophy only occasionally noted, however homozygosity for
the p.Arg707Trp mutation was recently associated with upper body adipose
overgrowth. We describe similar massive adipose overgrowth with suppressed leptin
expression in four further patients with biallelic MFN2 mutations and at least
one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1
negative unilocular adipocytes, with mitochondrial network fragmentation,
disorganised cristae, and increased autophagosomes. There was strong
transcriptional evidence of mitochondrial stress signalling, increased protein
synthesis, and suppression of signatures of cell death in affected tissue,
whereas mitochondrial morphology and gene expression were normal in skin
fibroblasts. These findings suggest that specific MFN2 mutations cause tissue
selective mitochondrial dysfunction with increased adipocyte proliferation and
survival, confirm a novel form of excess adiposity with paradoxical suppression
of leptin expression, and suggest potential targeted therapies.
PMID- 28414272
TI - Regulation of mitochondria-dynactin interaction and mitochondrial retrograde
transport in axons.
AB - Mitochondrial transport in axons is critical for neural circuit health and
function. While several proteins have been found that modulate bidirectional
mitochondrial motility, factors that regulate unidirectional mitochondrial
transport have been harder to identify. In a genetic screen, we found a zebrafish
strain in which mitochondria fail to attach to the dynein retrograde motor. This
strain carries a loss-of-function mutation in actr10, a member of the dynein
associated complex dynactin. The abnormal axon morphology and mitochondrial
retrograde transport defects observed in actr10 mutants are distinct from dynein
and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin
binding domain maintains its ability to bind mitochondria, arguing for a role for
Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies
implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde
transport. Together, this work identifies Actr10 as a factor necessary for
dynactin-mitochondria interaction, enhancing our understanding of how
mitochondria properly localize in axons.
PMID- 28414274
TI - Prepancreatic postduodenal portal vein.
PMID- 28414275
TI - A New Hypothesis on the Frequency Discrimination of the Cochlea.
AB - OBJECTIVE: Medial olivocochlear efferent (MOCE) neurons innervate outer hair
cells (OHCs) of the cochlea, which in turn leads to basilar membrane motion. We
hypothesized that MOCE-induced alterations in basilar membrane motion,
independent of traveling waves, is responsible for the cochlear frequency
discrimination of sound. MATERIALS AND METHODS: Eleven guinea pigs underwent
bilateral otoscopic and audiologic evaluations under general anesthesia. The
study comprised two parts. Part I (n=11) included spontaneous otoacoustic
emission (SOAE) recordings with or without contralateral pure-tone acoustic
stimuli (1 and 8 kHz) at 60 dB sound pressure level (SPL). Part II involved pure
tone (1 or 8 kHz) acoustic trauma in the right ears of two randomly selected
subgroups (G1: 1 kHz; n=4 and G8: 8 kHz; n=4). The remaining three animals served
as controls. After frequency-specific deafness was confirmed by distortion
product otoacoustic emission (DPOAE), SOAEs were recorded in the left ears in the
presence of a contralateral pure-tone (1 and 8 kHz) stimulus of 60 dB SPL.
Furthermore, the surface of the organ of Corti was examined by scanning electron
microscopy (SEM). RESULTS: The contralateral pure tone led to frequency-specific
activation in SOAEs in part I (without trauma) and part II (with trauma)
measurements. SEM showed heterogeneous OHC damage along the cochlea in
traumatized ears with pure tone. CONCLUSION: We suggest that MOCEs convey
acoustic information from traumatized ears to intact ears. Traumatized ears can
show frequency-specific activation in the presence of diffuse damage in OHCs that
excludes the passive transmission of the pressure wave from the perilymph to the
basilar membrane.
PMID- 28414273
TI - Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate
cartilage.
AB - Cartilaginous structures are at the core of embryo growth and shaping before the
bone forms. Here we report a novel principle of vertebrate cartilage growth that
is based on introducing transversally-oriented clones into pre-existing
cartilage. This mechanism of growth uncouples the lateral expansion of curved
cartilaginous sheets from the control of cartilage thickness, a process which
might be the evolutionary mechanism underlying adaptations of facial shape. In
rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing
limbs), the transverse integration of clonal columns determines the well-defined
diameter and resulting rod-like morphology. We were able to alter cartilage shape
by experimentally manipulating clonal geometries. Using in silico modeling, we
discovered that anisotropic proliferation might explain cartilage bending and
groove formation at the macro-scale.
PMID- 28414276
TI - Studying the Association between Sudden Hearing Loss and DNA N-Methyltransferase
1 (DNMT1) Genetic Polymorphism.
AB - OBJECTIVE: The aim of the present study was to investigate whether there was any
relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and
susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL
patients. MATERIAL AND METHODS: We investigated 90 patients diagnosed with ISSHL
and a control group composed of 75 age- and gender-matched healthy individuals.
DNA was extracted from the blood samples by phenol-chloroform method. Polymerase
chain reaction and restriction fragment length polymorphism methods were used for
the genotyping analysis of 4 regions of DNMT1. RESULTS: For rs2228612 single
nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were
81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients,
respectively. We observed a significant decrease in the frequency of GG genotype
in patients with ISSHL when compared with controls (p=0.027). The frequency of
GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls
and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly
increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we
found that individuals with the AA genotype had 2.47 times the risk for ISSHL
development than individuals with the GG genotype (p=0.41). The GAA haplotype may
constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence
interval: 0.28-25.03). CONCLUSION: This study's results showed that the AA
genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG
genotype could be a protective factor in rs2228612 polymorphism.
PMID- 28414277
TI - Waardenburg Syndrome: An Unusual Indication of Cochlear Implantation Experienced
in 11 Patients.
AB - OBJECTIVE: The aim of this study was to present the surgical findings of children
with Waardenburg syndrome (WS) and investigate speech development after cochlear
implantation in this unique group of patients. MATERIALS AND METHODS: A
retrospective chart review of the patients diagnosed with WS and implanted
between 1998 and 2015 was performed. Categories of auditory performance (CAP)
test were used to assess the auditory skills of these patients. CAP is a
nonlinear hierarchical scale used to rate a child's developing auditory
abilities. Preoperative test results and intraoperative surgical findings of
these patients have been presented. RESULTS: In total, 1835 cases were implanted
a tour institution, and 1210 of these were children. Among these implantees, 11
were diagnosed with WS (0.59% of all implantees). Four of the 11 patients showed
incomplete partition type 2bony labyrinth abnormality (Mondini deformity) and all
patients showed intraoperative gusher during cochleostomy, which was subsided
through routine interventions. No other complications occurred during surgery,
and all patients showed satisfactory CAP results in the late postoperative
period. CONCLUSION: Our experiences with cochlear implantation in patients with
WS showed that the procedure is safe and effective in this group of patients.
Surgeons should be aware of possible labyrinth malformations and intraoperative
problems such as gusher in these patients. In long term, auditory performances
may exhibit satisfactory results with optimal postoperative educational and
supportive measures.
PMID- 28414278
TI - Otoacoustic Emissions in Young Children with Autism.
AB - OBJECTIVE: The aim of this study is to investigate otoacoustic emissions (OAEs)
in young children with autism compared with those in an age-matched control
group. MATERIALS AND METHODS: Thirty-eight children with autism aged 3-6 years
and 27 typically developing (normally developing) control subjects participated
in this study. All the participants had normal hearing and middle-ear function.
Auditory brainstem responses were used to determine the hearing status in the
autism group. Transient-evoked otoacoustic emissions (TEOAEs) and distortion
product otoacoustic emissions (DPOAEs) were measured in the two groups. RESULTS:
The TEOAE response level was higher in the autism group. Analysis of the DPOAE
response showed that the mean emission levels at 1.5, 2 , 3, and 6 kHz and
signal/noise ratios at 2, 4, 6, and 8 kHz were higher in the autism group
(p<0.05). The greatest between-group differences were observed in the DPOAE
signal levels at 2, 3, and 6 kHz (p=0.000). No statistically significant
difference was found between the noise levels in the autism and control groups
(p>0.05). CONCLUSION: The emission responses in the autism group were higher than
those in the control group. The increase in DPOAEs at high frequencies may be
related to the higher outer cell activation in the autism group. Further studies
with larger sample sizes comprising younger children are needed to confirm the
result and investigate the possible association between the increased OAEs and
auditory sensitivity reported in autism.
PMID- 28414279
TI - Short-term Effects of Radioiodine Therapy on Auditory Function.
AB - OBJECTIVE: Radioiodine therapy (RIT) is frequently utilized as an adjunctive
treatment option for differentiated thyroid carcinoma following surgical
intervention. The side effects of RIT are considered to emerge as a result of
radioiodine accumulation in non-thyroidal tissues capable of iodine uptake. We
aimed to evaluate the effects of RIT on auditory function. MATERIALS AND METHODS:
Patients who had undergone total thyroidectomy and diagnosed to have
differentiated thyroid carcinoma were analyzed. Those who were given RIT were
included. Pure-tone audiometry and distortion product otoacoustic emission (DP
OAE) results were recorded along with patient demographics, RIT dose, and thyroid
hormone profiles, both before and 3 months after RIT. RESULTS: Here, 63 patients
were enrolled. Following RIT, audiometric thresholds at 0.25, 0.5, 4, and 8 kHz
in addition to pure-tone average increased significantly; however, the change in
DP-OAE results was not statistically significant at any frequency. The RIT dose
had no effect on auditory function. CONCLUSION: In this study, we found some
deleterious effects of RIT on audiometric thresholds, with no significant effect
on DP-OAE results.
PMID- 28414280
TI - Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Pediatric Patients
with Idiopathic Sudden Hearing Loss.
AB - OBJECTIVE: We investigated the significance of the neutrophil-to-lymphocyte and
platelet-to-lymphocyte ratios, which have recently been used in adults for the
prognosis of idiopathic sudden hearing loss (ISHL), in the prognosis of
idiopathic sudden hearing loss in a pediatric population. MATERIALS AND METHODS:
A total of 13 males and 8 females younger than19 years with idiopathic sudden
hearing loss were retrospectively examined between January 2008 and August
2016.The control group consisted of 12 healthy males and 12 healthy females.
Patients were divided into two groups: those who recovered after treatment and
those who did not. RESULTS: A statistical significance for the neutrophil-to
lymphocyte ratio was detected between the patient group and control group and
between patients who recovered and those who did not (p<0.05). No statistical
significance for the platelet-to-lymphocyte ratio was detected between the
patient group and control group and between patients with recovery and those
without recovery (p>0.05). CONCLUSION: The neutrophil-to-lymphocyte ratio is an
important marker for the prognosis of idiopathic sudden hearing loss in pediatric
patients, similar to its use in adult patients.
PMID- 28414281
TI - [Analysis of contribution of protein phosphorylation in the development of the
diseases].
AB - In recent decades, studies in the molecular origins of socially significant
diseases have made a big step forward with the development and using of high
performance methods in genomics and proteomics. Numerous studies in the framework
of the global program "Human Proteome" were aimed at the identification of all
possible proteins in various cell cultures and tissues, including cancer. One of
the objectives was to identify biomarkers - proteins with high specificity to
certain pathologies. However, in many cases, it is shown that the development of
the disease is not associated with the appearance of new proteins, but depends on
the level of gene expression or forming of proteoforms - splice variants, single
amino acid substitutions (SAP variants), and post-translational modifications
(PTM) of proteins. PTM may play a key role in the development of pathology
because they activate a variety of regulatory or structural proteins in the
majority of cell physiological processes. Phosphorylation is among the most
significant of these protein modifications.This review will describe methods for
analysis of protein phosphorylation used in the studies of such diseases as
cancer and neurodegenerative diseases, as well as examples of cases when the
modified proteins are involved directly to their development, and screening such
significant PTM is used for the diagnosis and choice of treatment.
PMID- 28414282
TI - [Pharmacometabonomics - the novel way to personalized drug therapy].
AB - The review is devoted to pharmacometabonomics - a new branch of science focused
on personalization of drug therapy through the comprehensive analysis of
metabolites of patient's biological fluids. It considers the history of
pharmacometabonomic, positioning to other "-omic" sciences, and system approach,
realized by this science, in determination of individual therapeutic dose of the
drugs and also a technical implementation of pharmacometabonomic based on direct
mass spectrometry of blood plasma metabolites. Special attention is paid to a
comparative analysis of pharmacometabonomics and other main approaches to
personalized therapy in the clinic, such as pharmacogenetics and therapeutic drug
monitoring. Finally, prospects of pharmacometabonomics applications in clinical
practice were also discussed.
PMID- 28414283
TI - [Prediction of protein thermostability from their primary structure: the current
state and development factors].
AB - The construction of proteins and peptides with desired properties, including
resistance to high temperatures, as well as optimization of their amino acid
composition, is an important and complex task, which attracts much attention in
various branches of the basic sciences, and also in biomedicine and
biotechnology. This raises the question: what method is more relevant for the at
the pilot stage of research in order to estimate the influence of the planned
amino acid substitutions on the thermostability of the resultant protein
construct? In this brief review we have classified existing basic practical and
theoretical approaches used in studies and predicting the thermal stability of
native and recombinant polypeptides. Particular attention has been paid to the
predictive potential of statistical methods for studying the thermodynamic
parameters of the primary protein structure and prospects of their use.
PMID- 28414284
TI - [Antineoplastic mechanisms of niclosamide-loaded nanoparticles in human
colorectal cancer cells].
AB - Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide
(PFN) and investigated molecular mechanisms underlying its antitumor activity
against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was
shown to be more cytotoxic against cancer cells and less cytotoxic against normal
cells (human embryonic lung fibroblasts) as compared to niclosamide. Both
niclosamide and its polymeric form caused mitochondrial damage (evaluated as a
decrease in rhodamine 123 accumulation) and increased the levels of reactive
oxygen species, particularly mitochondrial superoxide, resulting in the oxidative
damage to biomolecules. Furthermore, niclosamide and PFN induced G0/G1 cell cycle
arrest.
PMID- 28414285
TI - [Analysis of gene expression pattern in peripheral blood leukocytes during
experimental heat wave].
AB - The conditions of Moscow 2010 summer heat wave were simulated in an accommodation
module. Six healthy men aged from 22 to 46 years stayed in the module for 30
days. Measurements of gene expression in peripheral blood leukocytes before,
during and 3 day after simulated heat wave were performed using qRT-PCR. We
observed a shift in the expression level of certain genes after heat exposure for
a long time, and rapid return to the initial level, when volunteers leaved the
accommodation module. Eight genes were chosen to form the "heat expression
signature". EGR2, EGR3 were upregulated in all six volunteers, EGR1, SIRT1,
CYP51A1, MAPK9, BAG5, MNDA were upregulated in 5 volunteers.
PMID- 28414286
TI - [PCR analysis of the absolute number of copies of human chromosome 18 transcripts
in liver and HepG2 cells].
AB - Using reverse transcription in conjunction with the quantitative real-time PCR or
digital droplet PCR, the transcriptome profiling of human chromosome 18 has been
carried out in liver hepatocytes and hepatoblastoma cells (HepG2 cell line) in
terms of the absolute number of each transcript per cell. The transcript
abundance varies within the range of 0.006 to 9635 and 0.011 to 4819 copies per
cell for HepG2 cell line and hepatocytes, respectively. The expression profiles
for genes of chromosome 18 in hepatocytes and HepG2 cells were found to
significantly correlate: the Spearman's correlation coefficient was equal to
0.81. The distribution of frequency of transcripts over their abundance was
bimodal for HepG2 cells and unimodal for liver hepatocytes. Bioinformatic
analysis of the differential gene expression has revealed that genes of
chromosome 18, overexpressed in HepG2 cells compared to hepatocytes, are
associated with cell division and cell adhesion processes. It is assumed that the
enhanced expression of those genes in HepG2 cells is related to the proliferation
activity of cultured cells. The differences in transcriptome profiles have to be
taken into account when modelling liver hepatocytes with cultured HepG2 cells.
PMID- 28414287
TI - [Metabolic effects of combined introduction of adrenalin and blocker of
methanoprolol beta-adrenophyleters].
AB - The effect of combined administration of adrenaline (0.4 mg/kg, i.p.) and b1
blocker metoprolol (25 mg/kg) on the activity of glutathione peroxidase (GPO),
glutathione reductase (GR), catalase, adenosine deaminase (AD), AMP deaminase
(AMPD), 5c-nucleotidase (5cN), on the level ofmalonic dialdehyde (MDA) and
conjugated dienes (CD) was investigated. In blood adrenaline administration to
animals caused an increase in the activity of AMPD, AD, 5cN and GPO, and the
increase the level of CD in the blood increases. Metoprolol caused a more
pronounced increase in the activity of blood AMPD, AD, 5'N and the amount of CD.
In contrast to adrenaline, metoprolol decreased the MDA level of, and decreased
the activity of GPO and catalase. Combined administration of metoprolol and
adrenaline to animals was accompanied by an increase in the activity of AD, AMPD,
5cN, a decrease in the activity of GR, GPO, catalase, and a decrease in MDA in
the blood. In the heart, adrenaline injection was accompanied by an increase in
the MDA level, a decrease in 5cN activity and an increase in the ratio of the
activities of the enzymes AD+AMPD/5cN. Metoprolol injection reduced MDA and CD
levels and the activity of GR and GPO. The combined administration of metoprolol
and adrenaline in the heart was accompanied by activation of AD, AMPD and 5cN,
and a decrease in the amount of MDA and CD, and a decrease in the activity of GR,
GPO, and catalase. In the liver adrenaline caused an increase in MDA and DC
levels, activation of catalase, AD, AMPD, and 5cN. Metoprolol caused a decrease
in MDA and CD levels and activity of catalase and GPO, an increase in the
activity of AD and AMPD in the liver. Combined administration of adrenaline and
metoprolol reduced manifestations of the heart and liver oxidative stress
response as compared with administration of adrenaline alone.
PMID- 28414288
TI - [Redox-dependent mechanisms of regulation of breast epithelial cell
proliferation].
AB - Activation of free radical oxidation in different cell types, including breast
epithelial cells, may result in damage to macromolecules, in particular, proteins
taking part in regulation of cell proliferation and apoptosis. The glutathione,
glutaredoxin and thioredoxin systems play an essential role in maintaining
intracellular redox homeostasis. Due to this fact, modulation of cellular redox
status under the effect of an SH group inhibitor and an SH group protector may be
used as a model for studying the role of redox proteins and glutathione in
regulating cell proliferation in different pathological processes. In this study
we have evaluated the state of the thioredoxin, glutaredoxin and glutathione
systems as well as their role in regulating proliferation of HBL-100 breast
epithelial cells under redox status modulation with N-ethylmaleimide (NEM) and
1,4-dithioerythriol (DTE). Modulating the redox status of breast epithelial cells
under the effect of NEM and DTE influences the functional activity of glutathione
dependent enzymes, glutaredoxin, thioredoxin, and thioredoxin reductase through
changes in the GSH and GSSG concentrations. In HBL-100 cells under redox-status
modulation, we have found an increase in the number of cells in the S-phase of
the cell cycle and a decrease in the number of cells in the G0/G1 and G2/M
phases, as opposed to the values in the intact culture. The proposed model of
proliferative activity of cells under redox status modulation may be used for
development of new therapeutic approaches for treatment of diseases accompanied
by oxidative stress generation.
PMID- 28414289
TI - [Isolation and characterization of exosomes from blood plasma of breast cancer
and colorectal cancer patients].
AB - A simple approach for isolation of exosomes from the blood plasma, which allows
to obtain highly purified preparations of microvesicles no larger than 100 nm has
been proposed. The presence of different subpopulations of exosomes in the blood
plasma of healthy donors and cancer patients has been recognized. We found the
presence of the universal markers CD9, CD24 and CD81 on exosomes isolated from
blood plasma that can be used to their routine typing.
PMID- 28414290
TI - [The effect of isatin on protein-protein interactions between cytochrome b5 and
cytochromes P450].
AB - Cytochromes P450 (CYP) are involved in numerous biochemical processes including
metabolism of xenobiotics, biosynthesis of cholesterol, steroid hormones etc.
Since some CYP catalyze indol oxidation to isatin, we have hypothesized that
isatin can regulate protein-protein interactions (PPI) between components of the
CYP system thus representing a (negative?) feedback mechanism. The aim of this
study was to investigate a possible effect of isatin on interaction of human CYP
with cytochrome b5 (CYB5A). Using the optical biosensor test system employing
surface plasmon resonance (SPR) we have investigated interaction of immobilized
CYB5A with various CYP in the absence and in the presence of isatin. The SPR
based experiments have shown that a high concentration of isatin (270 mM)
increases Kd values for complexes CYB5A/CYP3A5 and CYB5A/CYP3A4 (twofold and
threefold, respectively), but has no influence on complex formation between CYB5A
and other CYP (including indol-metabolizing CYP2C19 and CYP2E1). Isatin injection
to the optical biosensor chip with the preformed molecular complex CYB5A/CYP3A4
caused a 30%-increase in its dissociation rate. Molecular docking manipulations
have shown that isatin can influence interaction of CYP3A5 or CYP3A4 with CYB5A
acting at the contact region of CYB5A/CYP.
PMID- 28414291
TI - Defects in DNA replication hit NK cells and neutrophils.
AB - Patients who present with unique immunological phenotypes provide an opportunity
to better understand defect-driving mutations. In this issue of the JCI,
Cottineau and colleagues characterize 5 individuals who exhibited growth
restriction, facial deformities, and a history of bacterial and viral infection.
Further characterization revealed that these patients were neutropenic and NK
cell deficient. These phenotypes were unexpectedly linked to mutations in the
gene encoding a subunit of the Go-Ichi-Ni-San (GINS) complex, which is essential
for DNA replication prior to cell division. Together, the results of this study
lay the groundwork for future studies to explore the role of DNA replication in
immune cell generation and function.
PMID- 28414292
TI - Dendritic cells expressing immunoreceptor CD300f are critical for controlling
chronic gut inflammation.
AB - Proinflammatory cytokine overproduction and excessive cell death, coupled with
impaired clearance of apoptotic cells, have been implicated as causes of failure
to resolve gut inflammation in inflammatory bowel diseases. Here we have found
that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f
play a crucial role in regulating gut inflammatory responses in a murine model of
colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate
sodium-induced colonic inflammation as a result of defects in dendritic cell
function that were associated with abnormal accumulation of apoptotic cells in
the gut. CD300f-deficient dendritic cells displayed hyperactive phagocytosis of
apoptotic cells, which stimulated excessive TNF-alpha secretion predominantly
from dendritic cells. This, in turn, induced secondary IFN-gamma overproduction
by colonic T cells, leading to prolonged gut inflammation. Our data highlight a
previously unappreciated role for dendritic cells in controlling gut homeostasis
and show that CD300f-dependent regulation of apoptotic cell uptake is essential
for suppressing overactive dendritic cell-mediated inflammatory responses,
thereby controlling the development of chronic gut inflammation.
PMID- 28414293
TI - Inherited GINS1 deficiency underlies growth retardation along with neutropenia
and NK cell deficiency.
AB - Inborn errors of DNA repair or replication underlie a variety of clinical
phenotypes. We studied 5 patients from 4 kindreds, all of whom displayed
intrauterine growth retardation, chronic neutropenia, and NK cell deficiency.
Four of the 5 patients also had postnatal growth retardation. The association of
neutropenia and NK cell deficiency, which is unusual among primary
immunodeficiencies and bone marrow failures, was due to a blockade in the bone
marrow and was mildly symptomatic. We discovered compound heterozygous rare
mutations in Go-Ichi-Ni-San (GINS) complex subunit 1 (GINS1, also known as PSF1)
in the 5 patients. The GINS complex is essential for eukaryotic DNA replication,
and homozygous null mutations of GINS component-encoding genes are embryonic
lethal in mice. The patients' fibroblasts displayed impaired GINS complex
assembly, basal replication stress, impaired checkpoint signaling, defective cell
cycle control, and genomic instability, which was rescued by WT GINS1. The
residual levels of GINS1 activity reached 3% to 16% in patients' cells, depending
on their GINS1 genotype, and correlated with the severity of growth retardation
and the in vitro cellular phenotype. The levels of GINS1 activity did not
influence the immunological phenotype, which was uniform. Autosomal recessive,
partial GINS1 deficiency impairs DNA replication and underlies intra-uterine (and
postnatal) growth retardation, chronic neutropenia, and NK cell deficiency.
PMID- 28414294
TI - Salt and water: not so simple.
AB - It has long been viewed that the maintenance of osmotic balance in response to
high salt intake is a passive process that is mediated largely by increased water
consumption to balance the salt load. Two studies in this issue of the JCI
challenge this notion and demonstrate that osmotic balance in response to high
salt intake involves a complex regulatory process that is influenced by hormone
fluctuation, metabolism, food consumption, water intake, and renal salt and water
excretion. Rakova et al. report the unexpected observation that long-term high
salt intake did not increase water consumption in humans but instead increased
water retention. Moreover, salt and water balance was influenced by
glucocorticoid and mineralocorticoid fluctuations. Kitada et al. extend upon
these findings in mouse models and determined that increased urea and a
corresponding increase in urea transporters in the renal medulla as the result of
increased protein intake promote the water retention that is needed to achieve
osmotic homeostasis. Together, the results of these two studies lay the
groundwork for future studies to determine how, in the face of chronic changes in
salt intake, humans maintain volume and osmotic homeostasis.
PMID- 28414295
TI - High salt intake reprioritizes osmolyte and energy metabolism for body fluid
conservation.
AB - Natriuretic regulation of extracellular fluid volume homeostasis includes
suppression of the renin-angiotensin-aldosterone system, pressure natriuresis,
and reduced renal nerve activity, actions that concomitantly increase urinary Na+
excretion and lead to increased urine volume. The resulting natriuresis-driven
diuretic water loss is assumed to control the extracellular volume. Here, we have
demonstrated that urine concentration, and therefore regulation of water
conservation, is an important control system for urine formation and
extracellular volume homeostasis in mice and humans across various levels of salt
intake. We observed that the renal concentration mechanism couples natriuresis
with correspondent renal water reabsorption, limits natriuretic osmotic diuresis,
and results in concurrent extracellular volume conservation and concentration of
salt excreted into urine. This water-conserving mechanism of dietary salt
excretion relies on urea transporter-driven urea recycling by the kidneys and on
urea production by liver and skeletal muscle. The energy-intense nature of
hepatic and extrahepatic urea osmolyte production for renal water conservation
requires reprioritization of energy and substrate metabolism in liver and
skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven
muscle catabolism, which are prevented by increasing food intake. This
natriuretic-ureotelic, water-conserving principle relies on metabolism-driven
extracellular volume control and is regulated by concerted liver, muscle, and
renal actions.
PMID- 28414296
TI - PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor
CD8+ T cells.
AB - Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and
the immunostimulatory molecule CD80 and functions as a checkpoint to regulate
immune responses. The interaction of PD-L1 with CD80 alone has been shown to
exacerbate the severity of graft-versus-host disease (GVHD), whereas
costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that
temporary depletion of donor CD4+ T cells early after hematopoietic cell
transplantation effectively prevents GVHD while preserving strong graft-versus
leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models. Depletion
of donor CD4+ T cells increased serum IFN-gamma but reduced IL-2 concentrations,
leading to upregulation of PD-L1 expression by recipient tissues and donor CD8+ T
cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+
T cells cause anergy, exhaustion, and apoptosis, thereby preventing GVHD. In
lymphoid tissues, the interactions of PD-L1 with CD80 augment CD8+ T cell
expansion without increasing anergy, exhaustion, or apoptosis, resulting in
strong GVL effects. These results indicate that the outcome of PD-L1-mediated
signaling in CD8+ T cells depends on the presence or absence of CD4+ T cells, the
nature of the interacting receptor expressed by CD8+ T cells, and the tissue
environment in which the signaling occurs.
PMID- 28414298
TI - Access granted: iRGD helps silicasome-encased drugs breach the tumor barrier.
AB - In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat
pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has
distinct advantages: it can improve the pharmacokinetics of the drug, enhance
efficacy, and reduce unwanted side effects. A drawback is that the large size of
nanoparticles restricts their access to the tumor interior. Liu and colleagues
show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of
enhancing tumor penetration by drugs, can overcome this limitation to a
substantial degree when administered together with the nanoparticles. Pancreatic
adenocarcinoma is a challenging malignancy to treat and in desperate need for
improved treatments; therefore, advances like this are most welcome.
PMID- 28414297
TI - Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy
for pancreatic cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some
improvement in overall survival has been achieved with the introduction of
nanocarriers that deliver irinotecan or paclitaxel. Although it is generally
assumed that nanocarriers rely principally on abnormal leaky vasculature for
tumor access, a transcytosis transport pathway that is regulated by neuropilin-1
(NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by
the cyclic tumor-penetrating peptide iRGD. In a KRAS-induced orthotopic PDAC
model, coadministration of iRGD enhanced the uptake of an irinotecan-loaded
silicasome carrier that comprises lipid bilayer-coated mesoporous silica
nanoparticles (MSNPs); this uptake resulted in enhanced survival and markedly
reduced metastasis. Further, ultrastructural imaging of the treated tumors
revealed that iRGD coadministration induced a vesicular transport pathway that
carried Au-labeled silicacomes from the blood vessel lumen to a perinuclear site
within cancer cells. iRGD-mediated enhancement of silicasome uptake was also
observed in patient-derived xenografts, commensurate with the level of NRP-1
expression on tumor blood vessels. These results demonstrate that iRGD enhances
the efficacy of irinotecan-loaded silicasome-based therapy and may be a suitable
adjuvant in nanoparticle-based treatments for PDAC.
PMID- 28414299
TI - An indirect route to repetitive actions.
AB - It is increasingly evident that there is a genetic contribution to autism
spectrum disorders (ASDs) and other neural disorders involving excessive
repetition of action sequences. Among the implicated genes in these disorders are
those encoding postsynaptic scaffolding proteins with roles in synaptic
transmission and plasticity. Several mouse models harboring synonymous mutations
have shown alterations in synaptic transmission within the striatum, which has
key roles in controlling actions and action sequences. In this issue of the JCI,
Wang and coworkers show that glutamatergic synaptic transmission onto striatal
projection neurons is weakened in mutant mice lacking the SH3 and multiple
ankyrin repeat domains 3 (SHANK3B) scaffolding protein, defective expression of
which has been implicated in ASDs. This synaptic alteration gives rise to
stronger activity in the indirect pathway accompanied by decreased dendritic
spines on the indirect pathway medium spiny projection neuron, indicative of
decreased numbers of glutamatergic synapses. Selectively enhancing activity in
this pathway reduced excessive repetitive grooming in the mutant mice. Changes in
glutamatergic input to striatal projection neurons have been observed in several
other murine ASD models and associated disorders. Thus, manipulation of the
function of the striatal indirect pathway may be a useful therapeutic target for
treating disorders characterized by excessive repetitive behaviors.
PMID- 28414300
TI - PD-L1 serves as a double agent in separating GVL from GVHD.
AB - Allogeneic hematopoietic cell transplantation (HCT) represents a potentially
curative treatment for a variety of hematologic malignancies due to the well
recognized graft-versus-leukemia/lymphoma (GVL) effect that is mediated by donor
derived alloreactive T cells. However, graft-versus-host disease (GVHD) is
mediated by the same T cells and remains a significant clinical problem
associated with substantial morbidity and mortality. In this issue of the JCI, Ni
and colleagues used several murine models of GVHD to evaluate the effect of CD4+
T cell depletion on GVL versus GVHD and revealed that depletion of CD4+ T cells
leads to the upregulation of PD-L1 by recipient tissues and donor CD8+ T cells.
Interaction of PD-L1 with PD-1 in GVHD-targeted tissues resulted in CD8+ T cell
exhaustion and apoptosis, thereby preventing GVHD, whereas PD-L1 interactions
with CD80 in lymphoid tissue promoted CD8+ T cell survival and expansion, thereby
enhancing the GVL response. By separating these seemingly similar alloreactive T
cell responses based on the context of interaction, the results of this study may
lay the groundwork for the development of effective clinical strategies to
enhance GVL while minimizing GVHD following allogeneic HCT.
PMID- 28414301
TI - Striatopallidal dysfunction underlies repetitive behavior in Shank3-deficient
model of autism.
AB - The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3
(SHANK3) is critical for the development and function of glutamatergic synapses.
Disruption of the SHANK3-encoding gene has been strongly implicated as a
monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and
social interaction deficits. Although basal ganglia dysfunction has been proposed
to underlie repetitive behaviors, few studies have provided direct evidence to
support this notion and the exact cellular mechanisms remain largely unknown.
Here, we utilized the Shank3B mutant mouse model of autism to investigate how
Shank3 mutation may differentially affect striatonigral (direct pathway) and
striatopallidal (indirect pathway) medium spiny neurons (MSNs) and its relevance
to repetitive grooming behavior in Shank3B mutant mice. We found that Shank3
deletion preferentially affects synapses onto striatopallidal MSNs.
Striatopallidal MSNs showed profound defects, including alterations in synaptic
transmission, synaptic plasticity, and spine density. Importantly, the repetitive
grooming behavior was rescued by selectively enhancing the striatopallidal MSN
activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of
designer receptors exclusively activated by designer drugs (DREADD). Our findings
directly demonstrate the existence of distinct changes between 2 striatal
pathways in a mouse model of autism and indicate that the indirect striatal
pathway disruption might play a causative role in repetitive behavior of Shank3B
mutant mice.
PMID- 28414302
TI - Increased salt consumption induces body water conservation and decreases fluid
intake.
AB - BACKGROUND: The idea that increasing salt intake increases drinking and urine
volume is widely accepted. We tested the hypothesis that an increase in salt
intake of 6 g/d would change fluid balance in men living under ultra-long-term
controlled conditions. METHODS: Over the course of 2 separate space flight
simulation studies of 105 and 205 days' duration, we exposed 10 healthy men to 3
salt intake levels (12, 9, or 6 g/d). All other nutrients were maintained
constant. We studied the effect of salt-driven changes in mineralocorticoid and
glucocorticoid urinary excretion on day-to-day osmolyte and water balance.
RESULTS: A 6-g/d increase in salt intake increased urine osmolyte excretion, but
reduced free-water clearance, indicating endogenous free water accrual by urine
concentration. The resulting endogenous water surplus reduced fluid intake at the
12-g/d salt intake level. Across all 3 levels of salt intake, half-weekly and
weekly rhythmical mineralocorticoid release promoted free water reabsorption via
the renal concentration mechanism. Mineralocorticoid-coupled increases in free
water reabsorption were counterbalanced by rhythmical glucocorticoid release,
with excretion of endogenous osmolyte and water surplus by relative urine
dilution. A 6-g/d increase in salt intake decreased the level of rhythmical
mineralocorticoid release and elevated rhythmical glucocorticoid release. The
projected effect of salt-driven hormone rhythm modulation corresponded well with
the measured decrease in water intake and an increase in urine volume with
surplus osmolyte excretion. CONCLUSION: Humans regulate osmolyte and water
balance by rhythmical mineralocorticoid and glucocorticoid release, endogenous
accrual of surplus body water, and precise surplus excretion. FUNDING: Federal
Ministry for Economics and Technology/DLR; the Interdisciplinary Centre for
Clinical Research; the NIH; the American Heart Association (AHA); the Renal
Research Institute; and the TOYOBO Biotechnology Foundation. Food products were
donated by APETITO, Coppenrath und Wiese, ENERVIT, HIPP, Katadyn, Kellogg, Molda,
and Unilever.
PMID- 28414303
TI - Development of potent class II transactivator gene delivery systems capable of
inducing de novo MHC II expression in human cells, in vitro and ex vivo.
AB - Class II transactivator (CIITA) induces transcription of major histocompatibility
complex (MHC) II genes and can potentially be used to improve genetic
immunotherapies by converting non-immune cells into cells capable of presenting
antigens to CD4+ T cells. However, CIITA expression is tightly controlled and it
remains unclear whether distinct non-immune cells differ in this transactivator
regulation. Here we describe the development of gene delivery systems capable of
promoting the efficient CIITA expression in non-immune cell lines and in primary
human cells of an ex vivo skin explant model. Different human cell types
undergoing CIITA overexpression presented high-level de novo expression of MHC
II, validating the delivery systems as suitable tools for the CIITA evaluation as
a molecular adjuvant for gene therapies.
PMID- 28414304
TI - Transforming activity and therapeutic targeting of C-terminal-binding protein 2
in Apc-mutated neoplasia.
AB - Overexpression of the transcriptional coregulators C-terminal binding proteins 1
and 2 (CtBP1 and 2) occurs in many human solid tumors and is associated with poor
prognosis. CtBP modulates oncogenic gene expression programs and is an emerging
drug target, but its oncogenic role is unclear. Consistent with this oncogenic
potential, exogenous CtBP2 transformed primary mouse and human cells to anchorage
independence similarly to mutant H-Ras. To investigate CtBP's contribution to in
vivo tumorigenesis, Apcmin/+ mice, which succumb to massive intestinal polyposis,
were bred to Ctbp2+/- mice. CtBP interacts with adenomatous polyposis coli (APC)
protein, and is stabilized in both APC-mutated human colon cancers and Apcmin/+
intestinal polyps. Ctbp2 heterozygosity increased the median survival of Apcmin/+
mice from 21 to 48 weeks, and reduced polyp formation by 90%, with Ctbp2+/-
polyps exhibiting reduced levels of beta-catenin and its oncogenic
transcriptional target, cyclin D1. CtBP's potential as a therapeutic target was
studied by treating Apcmin/+ mice with the CtBP small-molecule inhibitors 4
methylthio-2-oxobutyric acid and 2-hydroxy-imino phenylpyruvic acid, both of
which reduced polyposis by more than half compared with vehicle treatment.
Phenocopying Ctbp2 deletion, both Ctbp inhibitors caused substantial decreases in
the protein level of Ctbp2, as well its oncogenic partner beta-catenin, and the
effects of the inhibitors on CtBP and beta-catenin levels could be modeled in an
APC-mutated human colon cancer cell line. CtBP2 is thus a druggable transforming
oncoprotein critical for the evolution of neoplasia driven by Apc mutation.
PMID- 28414305
TI - SPOP regulates prostate epithelial cell proliferation and promotes ubiquitination
and turnover of c-MYC oncoprotein.
AB - The E3 ubiquitin ligase adaptor speckle-type POZ protein (SPOP) is frequently
dysregulated in prostate adenocarcinoma (PC), via either somatic mutations or
mRNA downregulation, suggesting an important tumour suppressor function. To
examine its physiologic role in the prostate epithelium in vivo, we generated
mice with prostate-specific biallelic ablation of Spop. These mice exhibited
increased prostate mass, prostate epithelial cell proliferation, and expression
of c-MYC protein compared to littermate controls, and eventually developed
prostatic intraepithelial neoplasia (PIN). We found that SPOPWT can physically
interact with c-MYC protein and, upon exogenous expression in vitro, can promote
c-MYC ubiquitination and degradation. This effect was attenuated in PC cells by
introducing PC-associated SPOP mutants or upon knockdown of SPOP via short
hairpin-RNA, suggesting that SPOP inactivation directly increases c-MYC protein
levels. Gene Set Enrichment Analysis revealed enrichment of Myc-induced genes in
transcriptomic signatures associated with SPOPMT. Likewise, we observed strong
inverse correlation between c-MYC activity and SPOP mRNA levels in two
independent PC patient cohorts. The core SPOPMT;MYCHigh transcriptomic response,
defined by the overlap between the SPOPMT and c-MYC transcriptomic programmes,
was also associated with inferior clinical outcome in human PCs. Finally, the
organoid-forming capacity of Spop-null murine prostate cells was more sensitive
to c-MYC inhibition than that of Spop-WT cells, suggesting that c-MYC
upregulation functionally contributes to the proliferative phenotype of Spop
knock-out prostates. Taken together, our data highlight SPOP as an important
regulator of luminal epithelial cell proliferation and c-MYC expression in
prostate physiology, identify c-MYC as a novel bona fide SPOP substrate, and help
explain the frequent inactivation of SPOP in human PC. We propose SPOPMT-induced
stabilization of c-MYC protein as a novel mechanism that can increase total c-MYC
levels in PC cells, in addition to amplification of c-MYC locus.
PMID- 28414306
TI - Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours.
AB - KRAS is one of the most frequently mutated oncogenes in human non-small cell lung
cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways
including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector
protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular
mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1
(PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF
with PHB1 at the plasma membrane is essential for CRAF activation. Here, we
demonstrate that PHB1 is highly expressed in NSCLC patients and correlates with
poor survival. Targeting of PHB1 with two chemical ligands (rocaglamide and
fluorizoline) inhibits epidermal growth factor (EGF)/RAS-induced CRAF activation.
Consistently, treatment with rocaglamide inhibited proliferation, migration and
anchorage-independent growth of KRAS-mutated lung carcinoma cell lines.
Surprisingly, rocaglamide treatment inhibited Ras-GTP loading in KRAS-mutated
cells as well as in EGF-stimulated cells. Rocaglamide treatment further prevented
the oncogenic growth of KRAS-driven lung cancer allografts and xenografts in
mouse models. Our results suggest rocaglamide as a RAS inhibitor and that
targeting plasma membrane-associated PHB1 with chemical ligands would be a viable
therapeutic strategy to combat KRAS-mediated NSCLCs.
PMID- 28414307
TI - Metabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition.
AB - The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has
firmly laid the cancer community to explore HDAC inhibition as a therapeutic
approach for cancer treatment. Hitting one HDAC member could yield clinical
benefit but this required a complete understanding of the functions of the
different HDAC members. Here we explored the consequences of specific HDAC5
inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron
dependent reactive oxygen species (ROS) production, ultimately leading to
apoptotic cell death as well as mechanisms of mitochondria quality control
(mitophagy and mitobiogenesis). Interestingly, adaptation of HDAC5-depleted cells
to oxidative stress passes through reprogramming of metabolic pathways towards
glucose and glutamine. Therefore, interference with both glucose and glutamine
supply in HDAC5-inhibited cancer cells significantly increases apoptotic cell
death and reduces tumour growth in vivo; providing insight into a valuable
clinical strategy combining the selective inhibition of HDAC5 with various
inhibitors of metabolism as a new therapy to kill cancer cells.
PMID- 28414308
TI - Complex regulation of LCoR signaling in breast cancer cells.
AB - Ligand-dependent corepressor (LCoR) is a transcriptional repressor of ligand
activated estrogen receptors (ERs) and other transcription factors that acts both
by recruiting histone deacetylases and C-terminal binding proteins. Here, we
first studied LCOR gene expression in breast cancer cell lines and tissues. We
detected two mRNAs variants, LCoR and LCoR2 (which encodes a truncated LCoR
protein). Their expression was highly correlated and localized in discrete
nuclear foci. LCoR and LCoR2 strongly repressed transcription, inhibited estrogen
induced target gene expression and decreased breast cancer cell proliferation. By
mutagenesis analysis, we showed that the helix-turn-helix domain of LCoR is
required for these effects. Using in vitro interaction, coimmunoprecipitation,
proximity ligation assay and confocal microscopy experiments, we found that
receptor-interacting protein of 140 kDa (RIP140) is a LCoR and LCoR2 partner and
that this interaction requires the HTH domain of LCoR and RIP140 N- and C
terminal regions. By increasing or silencing LCoR and RIP140 expression in human
breast cancer cells, we then showed that RIP140 is necessary for LCoR inhibition
of gene expression and cell proliferation. Moreover, LCoR and RIP140 mRNA levels
were strongly correlated in breast cancer cell lines and biopsies. In addition,
RIP140 positively regulated LCoR expression in human breast cancer cells and in
transgenic mouse models. Finally, their expression correlated with overall
survival of patients with breast cancer. Taken together, our results provide new
insights into the mechanism of action of LCoR and RIP140 and highlight their
strong interplay for the control of gene expression and cell proliferation in
breast cancer cells.
PMID- 28414309
TI - Tumor-derived fibulin-3 activates pro-invasive NF-kappaB signaling in
glioblastoma cells and their microenvironment.
AB - Molecular profiling of glioblastomas has revealed the presence of key signaling
hubs that contribute to tumor progression and acquisition of resistance. One of
these main signaling mechanisms is the nuclear factor-kappa B (NF-kappaB)
pathway, which integrates multiple extracellular signals into transcriptional
programs for tumor growth, invasion and maintenance of the tumor-initiating
population. We show here that an extracellular protein released by glioblastoma
cells, fibulin-3, drives oncogenic NF-kappaB in the tumor and increases NF-kappaB
activation in peritumoral astrocytes. Fibulin-3 expression correlates with a NF
kappaB-regulated 'invasive signature' linked to poorer survival, being a possible
tissue marker for regions of active tumor progression. Accordingly, fibulin-3
promotes glioblastoma invasion in a manner that requires NF-kappaB activation
both in the tumor cells and their microenvironment. Mechanistically, we found
that fibulin-3 activates the metalloprotease ADAM17 by competing with its
endogenous inhibitor, TIMP3. This results in sustained release of soluble tumor
necrosis factor alpha (TNFalpha) by ADAM17, which in turn activates TNF receptors
and canonical NF-kappaB signaling. Taken together, our results underscore fibulin
3 as a novel extracellular signal with strong activating effect on NF-kappaB in
malignant gliomas. Because fibulin-3 is produced de novo in these tumors and is
absent from the normal brain, we propose that targeting the fibulin-3/NF-kappaB
axis may provide a novel avenue to disrupt oncogenic NF-kappaB signaling in
combination therapies for malignant brain tumors.
PMID- 28414310
TI - Autophagy supports generation of cells with high CD44 expression via modulation
of oxidative stress and Parkin-mediated mitochondrial clearance.
AB - High CD44 expression is associated with enhanced malignant potential in
esophageal squamous cell carcinoma (ESCC), among the deadliest of all human
carcinomas. Although alterations in autophagy and CD44 expression are associated
with poor patient outcomes in various cancer types, the relationship between
autophagy and cells with high CD44 expression remains incompletely understood. In
transformed oesophageal keratinocytes, CD44Low-CD24High (CD44L) cells give rise
to CD44High-CD24-/Low (CD44H) cells via epithelial-mesenchymal transition (EMT)
in response to transforming growth factor (TGF)-beta. We couple patient samples
and xenotransplantation studies with this tractable in vitro system of CD44L to
CD44H cell conversion to investigate the functional role of autophagy in
generation of cells with high CD44 expression. We report that high expression of
the autophagy marker cleaved LC3 expression correlates with poor clinical outcome
in ESCC. In ESCC xenograft tumours, pharmacological autophagy inhibition with
chloroquine derivatives depletes cells with high CD44 expression while promoting
oxidative stress. Autophagic flux impairment during EMT-mediated CD44L to CD44H
cell conversion in vitro induces mitochondrial dysfunction, oxidative stress and
cell death. During CD44H cell generation, transformed keratinocytes display
evidence of mitophagy, including mitochondrial fragmentation, decreased
mitochondrial content and mitochondrial translocation of Parkin, essential in
mitophagy. RNA interference-mediated Parkin depletion attenuates CD44H cell
generation. These data suggest that autophagy facilitates EMT-mediated CD44H
generation via modulation of redox homeostasis and Parkin-dependent mitochondrial
clearance. This is the first report to implicate mitophagy in regulation of
tumour cells with high CD44 expression, representing a potential novel
therapeutic avenue in cancers where EMT and CD44H cells have been implicated,
including ESCC.
PMID- 28414311
TI - A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in
obesity.
AB - In obesity, inflammation of white adipose tissue (AT) is associated with
diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic
and energy-dissipating function mediated by beige adipocytes that express the
uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory
mechanism of beige adipogenesis in obesity that required direct adhesive
interactions between macrophages and adipocytes mediated by the integrin alpha4
and its counter-receptor VCAM-1, respectively; expression of the latter was
upregulated in obesity. This adhesive interaction reciprocally and concomitantly
modulated inflammatory activation of macrophages and downregulation of UCP1
expression dependent on the kinase Erk in adipocytes. Genetic or pharmacological
inactivation of the integrin alpha4 in mice resulted in elevated expression of
UCP1 and beige adipogenesis of subcutaneous AT in obesity. Our findings,
established in both mouse systems and human systems, reveal a self-sustained
cycle of inflammation-driven impairment of beige adipogenesis in obesity.
PMID- 28414313
TI - Alternative direct stem cell derivatives defined by stem cell location and graded
Wnt signalling.
AB - Adult stem cells provide a renewable source of differentiated cells for a wide
variety of tissues and generally give rise to multiple cell types. Basic
principles of stem cell organization and regulation underlying this behaviour are
emerging. Local niche signals maintain stem cells, while different sets of
signals act outside the niche to diversify initially equivalent stem cell
progeny. Here we show that Drosophila ovarian follicle stem cells (FSCs) produced
two distinct cell types directly. This cell fate choice was determined by the
anterior-posterior position of an FSC and by the magnitude of spatially graded
Wnt pathway activity. These findings reveal a paradigm of immediate
diversification of stem cell derivatives according to stem cell position within a
larger population, guided by a graded niche signal. We also found that FSCs
strongly resemble mammalian intestinal stem cells in many aspects of their
organization, including population asymmetry and dynamic heterogeneity.
PMID- 28414312
TI - High-resolution myogenic lineage mapping by single-cell mass cytometry.
AB - Muscle regeneration is a dynamic process during which cell state and identity
change over time. A major roadblock has been a lack of tools to resolve a
myogenic progression in vivo. Here we capitalize on a transformative technology,
single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell
and previously unrecognized progenitor populations that precede differentiation.
We discovered two cell surface markers, CD9 and CD104, whose combined expression
enabled in vivo identification and prospective isolation of stem and progenitor
cells. Data analysis using the X-shift algorithm paired with single-cell force
directed layout visualization defined a molecular signature of the activated stem
cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during
recovery from acute muscle injury. Our studies uncover the dynamics of skeletal
muscle regeneration in vivo and pave the way for the elucidation of the
regulatory networks that underlie cell-state transitions in muscle diseases and
ageing.
PMID- 28414314
TI - Cell competition with normal epithelial cells promotes apical extrusion of
transformed cells through metabolic changes.
AB - Recent studies have revealed that newly emerging transformed cells are often
apically extruded from epithelial tissues. During this process, normal epithelial
cells can recognize and actively eliminate transformed cells, a process called
epithelial defence against cancer (EDAC). Here, we show that mitochondrial
membrane potential is diminished in RasV12-transformed cells when they are
surrounded by normal cells. In addition, glucose uptake is elevated, leading to
higher lactate production. The mitochondrial dysfunction is driven by
upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively
regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the
surrounding normal cells, involving filamin, drives the Warburg-effect-like
metabolic alteration. Moreover, using a cell-competition mouse model, we
demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12
transformed cells from intestinal epithelia. These data indicate that non-cell
autonomous metabolic modulation is a crucial regulator for cell competition,
shedding light on the unexplored events at the initial stage of carcinogenesis.
PMID- 28414316
TI - Tuning crystallization pathways through sequence engineering of biomimetic
polymers.
AB - Two-step nucleation pathways in which disordered, amorphous, or dense liquid
states precede the appearance of crystalline phases have been reported for a wide
range of materials, but the dynamics of such pathways are poorly understood.
Moreover, whether these pathways are general features of crystallizing systems or
a consequence of system-specific structural details that select for direct versus
two-step processes is unknown. Using atomic force microscopy to directly observe
crystallization of sequence-defined polymers, we show that crystallization
pathways are indeed sequence dependent. When a short hydrophobic region is added
to a sequence that directly forms crystalline particles, crystallization instead
follows a two-step pathway that begins with the creation of disordered clusters
of 10-20 molecules and is characterized by highly non-linear crystallization
kinetics in which clusters transform into ordered structures that then enter the
growth phase. The results shed new light on non-classical crystallization
mechanisms and have implications for the design of self-assembling polymer
systems.
PMID- 28414315
TI - The EMT-activator Zeb1 is a key factor for cell plasticity and promotes
metastasis in pancreatic cancer.
AB - Metastasis is the major cause of cancer-associated death. Partial activation of
the epithelial-to-mesenchymal transition program (partial EMT) was considered a
major driver of tumour progression from initiation to metastasis. However, the
role of EMT in promoting metastasis has recently been challenged, in particular
concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in
pancreatic cancer. In contrast, we show here that in the same pancreatic cancer
model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model),
the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion
and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization
capacity and in particular phenotypic/metabolic plasticity of tumour cells,
probably causing the observed in vivo effects. Accordingly, we conclude that
different EMT-TFs have complementary subfunctions in driving pancreatic tumour
metastasis. Therapeutic strategies should consider these potential specificities
of EMT-TFs to target these factors simultaneously.
PMID- 28414317
TI - p16 controls epithelial cell growth and suppresses carcinogenesis through
mechanisms that do not require RB1 function.
AB - The p16/RB1 tumor suppressor pathway is inactivated in the vast majority, if not
all, human cancers. The current paradigm is that p16 and RB1 function in a linear
pathway to suppress tumorigenesis; however p16 is preferentially lost in human
cancers suggesting that p16 has critical tumor suppressive functions not mediated
through RB1. Carcinomas arise from transformed epithelial cells and account for
80% of adult malignancies highlighting the need to understand p16/RB1 pathway
function in organ epithelia. Lung cancer is the leading cause of cancer deaths
and is associated with p16/RB1 pathway deregulation. We demonstrate that p16 is
upregulated in the lung epithelium after Rb1 ablation in genetically engineered
mouse models. In contrast to fibroblasts, loss of RB1 family proteins, p107 or
p130, did not result in p16 induction, demonstrating that p16 suppression is a
unique RB1 pocket protein function in the lung epithelium in vivo. p16
upregulation did not induce cellular senescence but rather promoted survival of
RB1-deficient lung epithelial progenitor cells. Mechanistic studies show that p16
protects RB1-deficient cells from DNA damage. Consequently, additional loss of
p16 led to genetic instability and increased susceptibility to cellular
immortalization and transformation. Mice with combined RB1/p16-deficient lungs
developed lung tumors including aggressive metastatic lung cancers. These studies
identify p16 loss as a molecular event that causes genetic instability and
directly demonstrate that p16 protects against DNA damage in the absence of RB1
function providing an explanation for why p16 is preferentially targeted in human
cancers.
PMID- 28414319
TI - MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1alpha regulation.
PMID- 28414318
TI - Initial sites of hepadnavirus integration into host genome in human hepatocytes
and in the woodchuck model of hepatitis B-associated hepatocellular carcinoma.
AB - Hepatitis B virus (HBV) and the closely related woodchuck hepatitis virus (WHV)
are potent carcinogens that trigger development of primary hepatocellular
carcinoma (HCC). The initial sites of hepadnavirus-host genome integration, their
diversity and kinetics of formation can be central to virus persistence and the
initiation and progression of HCC. To recognize the nature of the very early
virus-host interactions, we explored de novo infection of human hepatocyte-like
HepaRG cells with authentic HBV and naive woodchucks with WHV. HepaRG were
analyzed from several minutes post exposure to HBV onwards, whereas woodchuck
liver biopsies at 1 or 3 h and 6 weeks post infection with WHV. Inverse PCR and
clonal sequencing of the amplicons were applied to identify virus-host genomic
junctions. HBV and WHV DNA and their replication intermediates became detectable
in one hour after virus exposure. Concomitantly, HBV DNA integration into various
host genes was detected. Notably, junctions of HBV X gene with retrotransposon
sequences, such as LINE1 and LINE2, became prominent shortly after infection. In
woodchucks, insertion of WHV X and preS sequences into host genome was evident at
1 and 3 h post infection (h.p.i.), confirming that hepadnavirus under natural
conditions integrates into hepatocyte DNA soon after invasion. The HBV and WHV X
gene enhancer II/core promotor sequence most often formed initial junctions with
host DNA. Moreover, multiple virus-virus DNA fusions appeared from 1 h.p.i.
onwards in both infected hepatocytes and woodchuck livers. In summary, HBV DNA
integrates almost immediately after infection with a variety of host's sequences,
among which tandemly repeating non-coding DNAs are common. This study revealed
that HBV can engage mobile genetic elements from the beginning of infection to
induce pro-oncogenic perturbations throughout the host genome. Such swift virus
insertion was also evident in natural hepadnaviral infection in woodchucks.
PMID- 28414320
TI - Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication
stress in cancer cells.
AB - Replication stress is a characteristic feature of cancer cells, which is resulted
from sustained proliferative signaling induced by activation of oncogenes or loss
of tumor suppressors. In cancer cells, oncogene-induced replication stress
manifests as replication-associated lesions, predominantly double-strand DNA
breaks (DSBs). An essential mechanism utilized by cells to repair replication
associated DSBs is homologous recombination (HR). In order to overcome
replication stress and survive, cancer cells often require enhanced HR repair
capacity. Therefore, the key link between HR repair and cellular tolerance to
replication-associated DSBs provides us with a mechanistic rationale for
exploiting synthetic lethality between HR repair inhibition and replication
stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in
replication and HR repair. Here we demonstrate that DNA2 is overexpressed in
pancreatic cancers, one of the deadliest and more aggressive forms of human
cancers, where mutations in the KRAS are present in 90-95% of cases. In addition,
depletion of DNA2 significantly reduces pancreatic cancer cell survival and
xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition.
Finally, we develop a robust high-throughput biochemistry assay to screen for
inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be
efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells
with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion,
including decreased DNA double strand break end resection and attenuation of HR
repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2
selectively attenuates the growth of various cancer cells with oncogene-induced
replication stress. Taken together, our findings open a new avenue to develop a
new class of anticancer drugs by targeting druggable nuclease DNA2. We propose
DNA2 inhibition as new strategy in cancer therapy by targeting replication
stress, a molecular property of cancer cells that is acquired as a result of
oncogene activation instead of targeting currently undruggable oncoprotein itself
such as KRAS.
PMID- 28414321
TI - An orthogonal single-molecule experiment reveals multiple-attempt dynamics of
type IA topoisomerases.
AB - Topoisomerases are enzymes that are involved in maintaining the topological state
of cellular DNA. Their dynamic characteristics remain poorly understood despite
numerous structural, biophysical and biochemical studies. Recent single-molecule
experiments revealed that an important feature of the type IA topoisomerase
mechanism is the presence of pauses between relaxation events. However, these
experiments could not determine whether the protein remains DNA bound during the
pauses or what relationship may exist between protein domain movements and
topological changes in the DNA. By combining two orthogonal single-molecule
techniques, we found that E. coli topoisomerase I constantly changes conformation
when attempting to modify the topology of DNA, but succeeds in only a fraction of
the attempts. Thus, its mechanism can be described as a series of DNA strand
passage attempts that culminate in a successful relaxation event.
PMID- 28414322
TI - Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required
for RBR ligase activity.
AB - RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from
RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which
lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a
catalytic RBR module but are usually autoinhibited and activated via distinct
mechanisms. Recent insights into Parkin regulation predict large, unknown
conformational changes during Parkin activation. However, current data on active
RBR ligases reflect the absence of regulatory domains. Therefore, it remains
unclear how individual RBR ligases are activated, and whether they share a common
mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin
complex, which shows that phosphoubiquitin binding induces movement in the 'in
between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation
of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding
promotes cooperation between Parkin molecules, which suggests a role for
interdomain association in the RBR ligase mechanism.
PMID- 28414323
TI - Pyrimidine tract-binding protein 1 mediates pyruvate kinase M2-dependent
phosphorylation of signal transducer and activator of transcription 3 and
oncogenesis in anaplastic large cell lymphoma.
AB - PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated
by numerous growth factor receptors and oncogenic tyrosine kinases including NPM
ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas
known as anaplastic large cell lymphoma, ALK-positive. Our previous work
demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major
metabolic shift to promote lymphomagenesis. In addition to its role in
metabolism, recent studies have shown that PKM2 promotes oncogenesis by
phosphorylating nuclear STAT3 (signal transducer and activator of transcription
3) and regulating transcription of genes involved in cell survival and
proliferation. We hypothesized that identification of novel PKM2 interactors
could provide additional insights into its expanding functional role in cancer.
To this end, immunocomplexes of FLAG-tagged PKM2 were isolated from NPM-ALK
positive ALCL (anaplastic large cell lymphoma) cells and subjected to liquid
chromatography tandem mass spectrometry (LC-MS/MS) which led to the
identification of polypyrimidine tract-binding protein (PTBP1) as a novel
interactor of PKM2. The interaction between PTBP1 and PKM2 was restricted to the
nucleus and was dependent on NPM-ALK mediated Y105 phosphorylation of PKM2.
Stable shRNA-mediated silencing of PTBP1 resulted in a marked decrease in pY105
PKM2 and pY705-STAT3 which led to decreased ALCL cell proliferation and colony
formation. Overall, our data demonstrate that PTBP1 interacts with PKM2 and
promotes ALCL oncogenesis by facilitating PKM2-dependent activation of STAT3
within the nucleus.
PMID- 28414324
TI - Correlation between histone acetylation and expression of Notch1 in human lung
carcinoma and its possible role in combined small-cell lung carcinoma.
AB - Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung
carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating
the molecular differences between SCLC and NSCLC could lead to a better
understanding of the pathogenesis of such neoplasms. Therefore, in this study, we
investigated the correlation between histone acetylation and Notch1 expression in
lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the
level of acetylated histone H3 around the promoter region of Notch1 in SCLC and
NSCLC cells. We then treated SCLC cells with trichostatin A (TSA) and
characterized the level of histone H3 acetylation at Notch1. In addition, TSA
treated cells were injected into immune-compromised mice, for analysis of the ex
vivo tumor xenograft phenotype. The level of acetylated histone H3 surrounding
the Notch1 promoter was lower in lung cancer cells not expressing Notch1. Tumors
originated from TSA-treated SCLC cells occasionally formed an epithelial-like
glandular arrangement of cells; with Notch1 expression and decreased expression
of neuroendocrine (NE) markers. Histone deacetylation around the promoter region
of Notch1 inhibits Notch1 protein expression in SCLC and the restoration of
Notch1 expression in SCLC leads to the concurrent appearance of epithelial-like
areas within the SCLC, which could provide a possible mechanism for histogenesis
of cSCLC.
PMID- 28414325
TI - Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug
therapy through the ABCC1 transporter.
AB - The poor response to drug therapy often seen in hepatocellular carcinoma requires
insight into the molecular interplay responsible for intrinsic or acquired drug
resistance. We previously demonstrated that the CD133-/EpCAM- subpopulation of
the Huh-7 hepatoma cell line features aberrant activation of the hedgehog
signaling (Hh) pathway and chemoresistance. The prevailing hypothesis of the
present study is that hedgehog signaling may govern expression of ATP-binding
cassette (ABC) transporters, which are responsible for drug resistance in the
CD133-/EpCAM- subpopulation. Our aim is to reveal the molecular interplay in the
mediation of drug resistance with a newly established Huh-7 subpopulation
featuring high Hh signaling activity and drug resistance. In this study,
chemoresistance was determined in a newly established Huh-7-DN subpopulation
featuring the CD133-/EpCAM- surface marker profile, aberrant expression of Hh
pathway, and epithelial-mesenchymal transition (EMT). Expression of ABC
transporter proteins (ABCB1, ABCC1, and ABCG2) and Hh transcription factor Gli
1/2 was evaluated with and without Hh signaling antagonists LDE225 or
itraconazole. We found that hedgehog signaling activity as determined by
transfection with a Gli-Lux reporter cassette and gene expression levels tended
to increase from Huh-7 CD133+/EpCAM+ to CD133-/EpCAM-, and the highest levels
were found in Huh-7-DN cells. The Huh-7-DN subpopulation exhibited
characteristics of EMT as evidenced by increased expression of vimentin and loss
of E-cadherin. Sorafenib significantly inhibited the viability of all
subpopulations except the Huh-7-DN subpopulation. Compared with other sorafenib
sensitive subpopulations, the Huh-7-DN subpopulation showed enhanced expression
of Hh transcription factor Gli-2 and ABCC1 transporter protein. Silencing Gli-2
by lentivirus harboring shRNA against Gli-2 or LDE225 significantly suppressed
expression of Gli-2 and ABCC1 genes in Huh-7-DN subpopulation. In conclusion,
aberrant hedgehog signaling activation is linked to poor differentiation,
epithelial-mesenchymal transition, and chemoresistance in the Huh-7-DN
subpopulation. Hedgehog signaling transcription factor Gli-2 appears to be the
primary regulator for drug sensitivity of hepatoma through the ABCC1 transporter.
PMID- 28414326
TI - Mesenchymal stem cells in obesity: insights for translational applications.
AB - Obesity is now a major public health problem worldwide. Lifestyle modification to
reduce the characteristic excess body adiposity is important in the treatment of
obesity, but effective therapeutic intervention is still needed to control what
has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been
withdrawn from market due to adverse side effects. Bariatric surgery therefore
remains the most effective therapy for severe cases, although such surgery is
invasive and researchers continue to seek new control strategies for obesity.
Mesenchymal stem cells (MSCs) are a major source of adipocyte generation, and
studies have been conducted into the potential roles of MSCs in treating obesity.
However, despite significant progress in stem cell research and its potential
applications for obesity, adipogenesis is a highly complex process and the
molecular mechanisms governing MSC adipogenesis remain ill defined. In
particular, successful clinical application of MSCs will require extensive
identification and characterization of the transcriptional regulators controlling
MSC adipogenesis. Since obesity is associated with the incidence of multiple
important comorbidities, an in-depth understanding of the relationship between
MSC adipogenesis and the comorbidities of obesity is also necessary to evaluate
the potential of effective and safe MSC-based therapies for obesity. In addition,
brown adipogenesis is an attractive topic from the viewpoint of therapeutic
innovation and future research into MSC-based brown adipogenesis could lead to a
novel breakthrough. Ongoing stem cell studies and emerging research fields such
as epigenetics are expected to elucidate the complicated mechanisms at play in
MSC adipogenesis and develop novel MSC-based therapeutic options for obesity.
This review discusses the current understanding of MSCs in adipogenesis and their
potential clinical applications for obesity.
PMID- 28414327
TI - A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially
useful for assessing colon cancer risk after screening colonoscopy.
AB - DCLK1 expression is critically required for maintaining growth of human colon
cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel
short isoform of DCLK1 (DCLK1-S; isoform 2) from beta-promoter of hDCLK1 gene,
while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(alpha)
promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells
(CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, we
succeeded in generating a monospecific DCLK1-S-Antibody (PS41014), which does not
cross-react with DCLK1-L, and specifically detects CSCs. Subcellular localization
of S/L-isoforms was examined by immune-electron-microscopy (IEM). Surprisingly,
besides plasma membrane and cytosolic fractions, S/L also localized to
nuclear/mitochondrial fractions, with pronounced localization of S-isoform in the
nuclei and mitochondria. Sporadic CRCs develop from adenomas. Screening
colonoscopy is used for detection/resection of growths, and
morphological/pathological criteria are used for risk assessment and
recommendations for follow-up colonoscopy. But, these features are not precise
and majority of the patients will never develop cancer. We hypothesized that
antibody-based assay(s), which identify CSCs, will significantly improve
prognostic value of morphological/pathological criteria. We conducted a pilot
retrospective study with PS41014-Ab, by staining archived adenoma specimens from
patients who developed (high-risk), or did not develop (low-risk) adenocarcinomas
within 10-15 years. PS41014-Ab stained adenomas from initial and follow-up
colonoscopies of high-risk patients, at significantly higher levels (three to
fivefold) than adenomas from low-risk patients, suggesting that PS41014-Ab could
be used as an additional tool for assessing CRC risk. CRC patients, with high
DCLK1-S-expressing tumors (by qRT-PCR), were reported to have worse overall
survival than low expressers. We now report that DCLK1-S-specific Ab may help to
identify high-risk patients at the time of index/screening colonoscopy.
PMID- 28414328
TI - Marginal zone B cells control the response of follicular helper T cells to a high
cholesterol diet.
AB - Splenic marginal zone B (MZB) cells, positioned at the interface between
circulating blood and lymphoid tissue, detect and respond to blood-borne
antigens. Here we show that MZB cells in mice activate a homeostatic program in
response to a high-cholesterol diet (HCD) and regulate both the differentiation
and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted
in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in
an ATF3-dependent manner and increased the interaction between MZB cells and pre
TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration
of TFH cell differentiation, reduced TFH abundance and suppression of the
proatherogenic TFH response. Our findings reveal a previously unsuspected role
for MZB cells in controlling the TFH-germinal center response to a cholesterol
rich diet and uncover a PDL1-dependent mechanism through which MZB cells use
their innate immune properties to limit an exaggerated adaptive immune response.
PMID- 28414329
TI - Alternatively activated macrophages do not synthesize catecholamines or
contribute to adipose tissue adaptive thermogenesis.
AB - Adaptive thermogenesis is the process of heat generation in response to cold
stimulation. It is under the control of the sympathetic nervous system, whose
chief effector is the catecholamine norepinephrine (NE). NE enhances
thermogenesis through beta3-adrenergic receptors to activate brown adipose tissue
and by 'browning' white adipose tissue. Recent studies have reported that
alternative activation of macrophages in response to interleukin (IL)-4
stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in
the catecholamine synthesis pathway, and that this activation provides an
alternative source of locally produced catecholamines during the thermogenic
process. Here we report that the deletion of Th in hematopoietic cells of adult
mice neither alters energy expenditure upon cold exposure nor reduces browning in
inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in
response to stimulation with IL-4, and conditioned media from IL-4-stimulated
macrophages failed to induce expression of thermogenic genes, such as uncoupling
protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore,
chronic treatment with IL-4 failed to increase energy expenditure in wild-type,
Ucp1-/- and interleukin-4 receptor-alpha double-negative (Il4ra-/-) mice. In
agreement with these findings, adipose-tissue-resident macrophages did not
express TH. Thus, we conclude that alternatively activated macrophages do not
synthesize relevant amounts of catecholamines, and hence, are not likely to have
a direct role in adipocyte metabolism or adaptive thermogenesis.
PMID- 28414330
TI - HIV persistence in tissue macrophages of humanized myeloid-only mice during
antiretroviral therapy.
AB - Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in
its hosts and is never eradicated. One major barrier to eradication is that the
virus infects multiple cell types that may individually contribute to HIV
persistence. Tissue macrophages are critical contributors to HIV pathogenesis;
however, their specific role in HIV persistence during long-term suppressive ART
has not been established. Using humanized myeloid-only mice (MoM), we demonstrate
that HIV infection of tissue macrophages is rapidly suppressed by ART, as
reflected by a rapid drop in plasma viral load and a dramatic decrease in the
levels of cell-associated viral RNA and DNA. No viral rebound was observed in the
plasma of 67% of the ART-treated animals at 7 weeks after ART interruption, and
no replication-competent virus was rescued from the tissue macrophages obtained
from these animals. In contrast, in a subset of animals (~33%), a delayed viral
rebound was observed that is consistent with the establishment of persistent
infection in tissue macrophages. These observations represent the first direct
evidence, to our knowledge, of HIV persistence in tissue macrophages in vivo.
PMID- 28414331
TI - A new fate mapping system reveals context-dependent random or clonal expansion of
microglia.
AB - Microglia constitute a highly specialized network of tissue-resident immune cells
that is important for the control of tissue homeostasis and the resolution of
diseases of the CNS. Little is known about how their spatial distribution is
established and maintained in vivo. Here we establish a new multicolor
fluorescence fate mapping system to monitor microglial dynamics during steady
state and disease. Our findings suggest that microglia establish a dense network
with regional differences, and the high regional turnover rates found challenge
the universal concept of microglial longevity. Microglial self-renewal under
steady state conditions constitutes a stochastic process. During pathology this
randomness shifts to selected clonal microglial expansion. In the resolution
phase, excess disease-associated microglia are removed by a dual mechanism of
cell egress and apoptosis to re-establish the stable microglial network. This
study unravels the dynamic yet discrete self-organization of mature microglia in
the healthy and diseased CNS.
PMID- 28414332
TI - Comprehensive transcriptome analysis of neocortical layers in humans, chimpanzees
and macaques.
AB - While human cognitive abilities are clearly unique, underlying changes in brain
organization and function remain unresolved. Here we characterized the
transcriptome of the cortical layers and adjacent white matter in the prefrontal
cortexes of humans, chimpanzees and rhesus macaques using unsupervised sectioning
followed by RNA sequencing. More than 20% of detected genes were expressed
predominantly in one layer, yielding 2,320 human layer markers. While the bulk of
the layer markers were conserved among species, 376 switched their expression to
another layer in humans. By contrast, only 133 of such changes were detected in
the chimpanzee brain, suggesting acceleration of cortical reorganization on the
human evolutionary lineage. Immunohistochemistry experiments further showed that
human-specific expression changes were not limited to neurons but affected a
broad spectrum of cortical cell types. Thus, despite apparent histological
conservation, human neocortical organization has undergone substantial changes
affecting more than 5% of its transcriptome.
PMID- 28414334
TI - Interband cascade laser-based optical transfer standard for atmospheric carbon
monoxide measurements.
AB - We report on an interband cascade laser (ICL)-absorption spectrometer for
absolute, calibration-free, atmospheric CO amount fraction measurements,
addressing direct traceability of the results. The system combines first
principles direct tunable diode laser absorption spectroscopy (dTDLAS) with a
metrological validation. Using a multipath cell with 76 m path length, our
detection limit is 0.5 nmol/mol at Deltat=14 s. The system is highly linear
(slope: 0.999+/-0.008) in the amount fraction range of 0.1-1000 MUmol/mol and
thus is interesting for industrial as well as environmental applications. The
sensor repeatability at 300 nmol/mol is 0.06 nmol/mol (with Deltat=10 min). The
sensor's absolute response is in excellent agreement with the gravimetric values
of a set of primary gas standards used to test the sensor accuracy. The relative
expanded uncertainty (k=2) of the measured CO amount fraction is 2.8%. Due to
this performance and the calibration-free approach, the spectrometer may be used
as an optical transfer standard (OTS) if gas standards are for whatever reason
not available or applicable, e.g., for airborne instruments. Our dTDLAS approach
has shown excellent stability and accuracy in H2O detection [Appl.
Phys. B116, 883 (2014)APPCDL0721-726910.1007/s00340-014-5775-4] even when
compared to primary standards. We therefore deduce that the ICL spectrometer
(after its adaptation to field conditions, similar to our H2O
spectrometers) has good potential to meet the 2 nmol/mol compatibility goal
stated by the World Meteorological Organization for atmospheric CO measurements,
and serve as an OTS which does not need frequent calibrations using reference
gases.
PMID- 28414333
TI - Dynamic hidden states underlying working-memory-guided behavior.
AB - Recent theoretical models propose that working memory is mediated by rapid
transitions in 'activity-silent' neural states (for example, short-term synaptic
plasticity). According to the dynamic coding framework, such hidden state
transitions flexibly configure memory networks for memory-guided behavior and
dissolve them equally fast to allow forgetting. We developed a perturbation
approach to measure mnemonic hidden states in an electroencephalogram. By
'pinging' the brain during maintenance, we show that memory-item-specific
information is decodable from the impulse response, even in the absence of
attention and lingering delay activity. Moreover, hidden memories are remarkably
flexible: an instruction cue that directs people to forget one item is sufficient
to wipe the corresponding trace from the hidden state. In contrast, temporarily
unattended items remain robustly coded in the hidden state, decoupling
attentional focus from cue-directed forgetting. Finally, the strength of hidden
state coding predicts the accuracy of working-memory-guided behavior, including
memory precision.
PMID- 28414335
TI - Uncertainty quantification and design-of-experiment in absorption-based aqueous
film parameter measurements using Bayesian inference.
AB - Diode laser-based multi-wavelength near-infrared (NIR) absorption in aqueous
films is a promising diagnostic for making temporally resolved, simultaneous
measurements of film thickness, temperature, and concentration of a solute. Our
previous work in aqueous urea solutions aimed at determining simultaneously two
of these system parameters, while the third one must be fixed or specified by
additional measurements. The current work presents a simultaneous NIR absorption
based multi-parameter measurement of thickness, temperature, and solute
concentration coupled with the Bayesian methodology that is used to infer
probability densities for the obtained data. The Bayesian analysis is based on a
temperature- and concentration-dependent spectral database generated with a
Fourier transform infrared spectrometer in the range 5500-8000 cm-1
for water with variable temperature and urea concentration. The concept was first
validated with measurements using a calibration cell. Probability densities in
the measured parameters were quantified using a Markov chain Monte Carlo
algorithm, which were used to derive credibility intervals. As a practical
demonstration, the temporal variation of film thickness, urea concentration, and
liquid temperature were recorded during evaporation of a liquid film deposited on
a transparent heated quartz plate.
PMID- 28414336
TI - Study of propagation of vortex beams in aerosol optical medium.
AB - A theoretical and experimental study of the propagation of vortex laser beams in
a random aerosol medium is presented. The theoretical study is based on the
extended Huygens-Fresnel principle with the generation of a random field, using
the fast Fourier transform. The simulation shows that the stability of vortex
beams to fluctuations of an optical medium falls with rising order of optical
vortices. Moreover, a coherence length (radius) of the random medium is of great
importance. The coherence radius extension affects adversely the conservation of
a beam structure in the random medium. During further free-space propagation,
increasing coherence enables reduction of the negative effects of fluctuations
for beams with high-value topological charges. Experimental studies in the random
aerosol medium have shown that at small distances vortex beams mostly demonstrate
lower stability than a Gaussian beam. However, at considerable distances, vortex
beams start to demonstrate greater stability that may be explained by their
capacity to be regenerated after they passed obstacles.
PMID- 28414337
TI - Development of an incoherent broad-band cavity-enhanced aerosol extinction
spectrometer and its application to measurement of aerosol optical
hygroscopicity.
AB - We report on the development of a blue light-emitting-diode-based incoherent
broad-band cavity-enhanced absorption spectroscopy (IBBCEAS) instrument for the
measurement of the aerosol extinction coefficient at lambda=461 nm. With an
effective absorption path length of 2.8 km, an optimum detection limit of 0.05
Mm-1 (5*10-10 cm-1) was achieved with an
averaging time of 84 s. The baseline drift of the developed spectrometer was
about +/-0.3 Mm-1 over 2.5 h (1sigma standard deviation). The
performance of the system was evaluated with laboratory-generated monodispersed
polystyrene latex (PSL) spheres. The retrieved complex refractive index of PSL
agreed well with previously reported values. The relative humidity (RH)
dependence of the aerosol extinction coefficient was measured using IBBCEAS. The
measured extinction enhancement factor values for 200 nm dry ammonium sulphate
particles at different RH were in good agreement with the modeled values. Field
performance of the aerosol extinction spectrometer was demonstrated at the Hefei
Radiation Observatory site.
PMID- 28414338
TI - Open-path spectroscopic methane detection using a broadband monolithic
distributed feedback-quantum cascade laser array.
AB - Methane is a powerful greenhouse gas that has both natural and anthropogenic
sources. The ability to measure methane using an integrated path length approach
such as an open/long-path length sensor would be beneficial in several
environments for examining anthropogenic and natural sources, including tundra
landscapes, rivers, lakes, landfills, estuaries, fracking sites, pipelines, and
agricultural sites. Here a broadband monolithic distributed feedback-quantum
cascade laser array was utilized as the source for an open-path methane sensor.
Two telescopes were utilized for the launch (laser source) and receiver
(detector) in a bistatic configuration for methane sensing across a 50 m path
length. Direct-absorption spectroscopy was utilized with intrapulse tuning.
Ambient methane levels were detectable, and an instrument precision of 70 ppb
with 100 s averaging and 90 ppb with 10 s averaging was achieved. The sensor
system was designed to work "off the grid" and utilizes batteries that are
rechargeable with solar panels and wind turbines.
PMID- 28414339
TI - Coherent anti-Stokes Raman spectroscopy measurement of ethylene in combustion.
AB - Width-increased dual-pump enhanced coherent anti-Stokes Raman spectroscopy
(WIDECARS) has been developed for spatially and temporally resolved simultaneous
measurement of temperature and mole fraction of most major species in ethylene
air flames. This paper describes a method to infer coherent anti-Stokes Raman
spectroscopy complex susceptibility distributions of the nu3 band of
ethylene from WIDECARS spectra measured in heated mixtures of ethylene and air,
and to use such distributions to fit experimental WIDECARS spectra in an ethylene
air flame. The method is used to measure mole fraction ethylene in a dual-mode
supersonic combustor burning premixed ethylene and air with single-laser-shot
precision (one standard deviation) of +/-0.0025 (absolute).
PMID- 28414340
TI - Comparison of chirped-probe-pulse and hybrid femtosecond/picosecond coherent anti
Stokes Raman scattering for combustion thermometry.
AB - A comparison is made between two ultrashort-pulse coherent anti-Stokes Raman
scattering (CARS) thermometry techniques-hybrid femtosecond/picosecond (fs/ps)
CARS and chirped-probe-pulse (CPP) fs-CARS-that have become standards for high
repetition-rate thermometry in the combustion diagnostics community. These two
variants of fs-CARS differ only in the characteristics of the ps-duration probe
pulse; in hybrid fs/ps CARS a spectrally narrow, time-asymmetric probe pulse is
used, whereas a highly chirped, spectrally broad probe pulse is used in CPP fs
CARS. Temperature measurements were performed using both techniques in near
adiabatic flames in the temperature range 1600-2400 K and for probe time delays
of 0-30 ps. Under these conditions, both techniques are shown to exhibit similar
temperature measurement accuracies and precisions to previously reported values
and to each other. However, it is observed that initial calibration fits to the
spectrally broad CPP results require more fitting parameters and a more robust
optimization algorithm and therefore significantly increased computational cost
and complexity compared to the fitting of hybrid fs/ps CARS data. The optimized
model parameters varied more for the CPP measurements than for the hybrid fs/ps
measurements for different experimental conditions.
PMID- 28414341
TI - Laser-induced atomic emission of silicon nanoparticles during laser-induced
heating.
AB - The temporal luminescence behavior of silicon atoms during and after laser
heating of gas-borne silicon nanoparticles was investigated. Silicon
nanoparticles were formed in the exhaust stream of a microwave plasma reactor at
100 mbar. The observed prompt atomic line intensities correspond with thermal
excitation of the evaporated species. A prompt signal at 251.61 and 288.15 nm
originating from the 3s23p2->3s23p4s transitions
showed a lifetime of 16 ns that matches the documented excited-state lifetime for
the respective transitions. A secondary delayed signal contribution with similar
peak intensities was observed commencing approximately 100-300 ns after the laser
pulse and persisting for hundreds of nanoseconds. This signal contribution is
attributed to electron impact excitation or recombination after electron impact
ionization of the silicon evaporated as a consequence of the laser heating of the
plasma leading to non-thermal population of electronically excited silicon. The
observations support a nanoparticle evaporation model that can be used to recover
nanoparticle sizes from time-resolved LII data.
PMID- 28414342
TI - Laser induced thermal lens microscopy for highly sensitive determination of
captopril.
AB - In this work, a combined flow injection-photo thermal lens microscopy (FI-PTLM)
system was used for highly sensitive determination of captopril as an angiotensin
converting enzyme inhibitor. Captopril has no absorption in the visible range,
but due to its thiol group could interact with gold nanoparticles (GNPs). GNPs,
because of their surface plasmon resonance (SPR), have absorption in the visible
range, but their interaction with a low concentration of captopril shows no
effective change in UV-Vis spectrophotometry because their aggregation is slight.
On the contrary, at the same condition, the PTLM with a visible light source
enables sensitive measurement of this compound. The thiol group of captopril
binds to the surface of GNPs and decreases the SPR. At the optimum condition in
the focal volume of 2.68 fL (f=10-15), the obtained range of linearity
was 50-800 nM. The developed method was successfully applied for the
determination of captopril in human serum and pharmaceutical samples.
PMID- 28414343
TI - Effect of hydrocarbon molecular decomposition on palladium-assisted laser-induced
plasma ablation.
AB - The Q-switched Nd:YAG laser is focused on a palladium target in the control
chamber filled with various hydrocarbon atmospheres (C1-C4) to investigate their
effect on the palladium ablated mass, gas reaction products, and corresponding
plasma parameters (such as electron density Ne and plasma temperature
Te) during molecular decomposition. The plasma parameters arise mainly
from the Pd nanocatalytic activity during the laser-induced plasma process. We
compare synthetic air atmosphere to hydrocarbon media to understand how the
latter generates excess heat via oxygen-free exothermic (recombination)
reactions. Subsequently, this gives rise to more energetic plasma and higher
temperature, regarding the large amount of nanoparticles released into the
plasma. The dynamics of the decomposition/recombination events accompany the
nanocatalyst activity, leading to soot deposition all over the chamber.
PMID- 28414344
TI - Measurement of thickness of highly inhomogeneous crude oil slicks.
AB - As part of the Deepwater Horizon toxicity testing program, a number of
laboratories generated oil slicks in the laboratory to study potential toxic
effects of these oil slicks on aquatic organisms. Understanding the details of
how these slicks affect aquatic organisms requires careful correlation between
slick thickness and the observed detrimental effects. Estimating oil film
thickness on water can be challenging since the traditional color-based technique
used in the field is very imprecise. Also, as we demonstrate here, the films
formed on the water surface are highly nonuniform on a microscale level, and thus
uniform thin film thickness measurement techniques based on optical interference
do not work. In this paper, we present a method that estimates the local
thickness of weathered oil slicks formed on artificial seawater using light
transmission and Beer-Lambert's law. Here, we demonstrate results of careful
calibration together with the actual thickness estimation. Due to the
heterogeneity of the slicks formed, we present slick thickness as a range of
thicknesses collected from multiple points within the oil slick. In all the
experiments we used oil samples provided by the Natural Resource Damage
Assessment toxicity testing program for the Deepwater Horizon oil spill.
Therefore, this study has an important practical value and successfully addresses
unique challenges related to measurements involving complex, viscous, paste-like
heterogeneous substances such as weathered crude oil.
PMID- 28414345
TI - Three-color vibrational CARS thermometry of fuel-rich ethylene/air flames using a
potassium gadolinium tungstate Raman-active crystal as a source of narrowband
probe radiation.
AB - Three-color broadband vibrational coherent anti-Stokes Raman scattering (CARS)
temperature measurements were carried out in laminar fuel-rich sooting
ethylene/air flames. Stimulated Raman scattering (SRS) of a picosecond pump laser
pulse in a Raman-active potassium gadolinium tungstate
[KGd(WO4)2] crystal was employed as a source of narrowband
probe radiation. In the three-color CARS experiment, this wavelength-shifted
radiation enables N2-based vibrational CARS temperature measurements
in sooting flames free of the signal interference with the absorption/emission
bands of the flame intermediate radicals C2. Spatial temperature
profiles for different fuel-rich atmospheric pressure ethylene/air flames are
presented in comparison with the results of two-color broadband vibrational and
dual-broadband pure rotational CARS temperature measurements. The comparison
shows the suitability of the three-color CARS measurement technique employing the
KGd(WO4)2 crystal for accurate, C2 interference
free, temperature measurements in sooting flames.
PMID- 28414346
TI - Mixture-fraction measurements with femtosecond-laser electronic-excitation
tagging.
AB - Tracer-free mixture-fraction measurements were demonstrated in a jet using
femtosecond-laser electronic-excitation tagging. Measurements were conducted
across a turbulent jet at several downstream locations both in a pure-nitrogen
jet exiting into an air-nitrogen mixture and in a jet containing an air-nitrogen
mixture exiting into pure nitrogen. The signal was calibrated with known
concentrations of oxygen in nitrogen. The spatial resolution of the measurement
was ~180 MUm. The measurement uncertainty ranged from 5% to 15%, depending on
the mixture fraction and location within the beam, under constant temperature and
pressure conditions. The measurements agree with a mixture fraction of unity
within the potential core of the jet and transition to the self-similar region.
PMID- 28414347
TI - High-resolution Fourier transform measurements of line strengths in the
0002-0000 main isotopologue band of nitrous oxide.
AB - Nitrous oxide (N2O) is a key greenhouse gas and a major ozone
depleting anthropogenic pollutant monitored by the total carbon column observing
network (TCCON) in the 0002-0000-band of its main
isotopologue. Here, we present highly accurate line strengths for this window
determined using Fourier transform infrared spectroscopy with pressure,
temperature, and optical path length being metrologically traceable to the SI.
The obtained results agree with previous studies within the given uncertainties.
Depending on the respective rovibrational transition, the present uncertainties
could be reduced by a factor of 5 to 83 in comparison to literature data.
PMID- 28414348
TI - Optical ray tracing method for simulating beam-steering effects during laser
diagnostics in turbulent media.
AB - In most coherent spectroscopic methods used in gas-phase laser diagnostics,
multiple laser beams are focused and crossed at a specific location in space to
form the probe region. The desired signal is then generated as a result of
nonlinear interactions between the beams in this overlapped region. When such
diagnostic schemes are implemented in practical devices having turbulent reacting
flow fields with refractive index gradients, the resulting beam steering can give
rise to large measurement uncertainties. The objective of this work is to
simulate beam-steering effects arising from pressure and temperature gradients in
gas-phase media using an optical ray tracing approach. The ZEMAX OpticStudio
software package is used to simulate the beam crossing and uncrossing effects in
the presence of pressure and temperature gradients, specifically the conditions
present in high-pressure, high-temperature combustion devices such as gas turbine
engines. Specific cases involving two-beam and three-beam crossing configurations
are simulated. The model formulation, the effects of pressure and temperature
gradients, and the resulting beam-steering effects are analyzed. The results show
that thermal gradients in the range of 300-3000 K have minimal effects, while
pressure gradients in the range of 1-50 atm result in pronounced beam steering
and the resulting signal fluctuations in the geometries investigated. However,
with increasing pressures, the temperature gradients can also have a pronounced
effect on the resultant signal levels.
PMID- 28414349
TI - Second-harmonic generation of a dual-frequency laser in a MgO:PPLN crystal.
AB - A dual-frequency CW laser at a wavelength of 1.064 MUm is frequency doubled in a
MgO:PPLN nonlinear crystal. The fundamental dual-frequency laser has a tunable
beat note from 125 MHz to 175 MHz. A laser-diode pumped fiber amplifier is used
to amplify the dual-frequency fundamental output to a maximum power of 50 W
before frequency doubling. The maximum output power of the green light is 1.75 W
when the input fundamental power is 12 W, corresponding to a frequency doubling
efficiency of 14.6%. After frequency doubling, green light with modulation
frequencies in two bands from 125 MHz to 175 MHz and from 250 MHz to 350 MHz is
achieved simultaneously. The relative intensities of the beat notes at the two
bands can be adjusted by changing the relative intensities at different
frequencies of the fundamental light. The spectral width and frequency
stabilities of the beat notes in fundamental wave and green light are also
measured, respectively. The modulated green light has potential applications in
underwater ranging, communication, and imaging.
PMID- 28414350
TI - Cr:ZnS saturable absorber passively Q-switched mode-locking Tm,Ho:LLF laser.
AB - We first report on a diode-end-pumped passively Q-switched mode-locking Tm,Ho:LLF
laser at 2053 nm by using a Cr:ZnS saturable absorber. A stable Q-switched mode
locking pulse train with a nearly 100% modulation depth was achieved. The
repetition frequency of the Q-switched pulse envelope increased from 0.5 to 12.3
kHz with increasing pump power from 1 to 4.36 W. The maximum average output power
of 145 mW was obtained, and the width of the mode-locked pulse was estimated to
be less than 682 ps with a 250 MHz repetition frequency within a Q-switched pulse
envelope of about 700 ns.
PMID- 28414351
TI - Phase-matching properties of BaGa4Se7 for SHG and SFG in
the 0.901-10.5910 MUm range.
AB - We report new experimental results on the phase-matching properties of a
BaGa4Se7 crystal for harmonic generation of a Nd:YAG laser
pumped AgGaS2 optical parametric oscillator (OPO) and a CO2
laser in the 0.901-10.5910 MUm range. In addition, we present new Sellmeier
equations that provide a good reproduction of the present experimental results as
well as the published data points for a Nd:YAG laser-pumped OPO and an optical
parametric amplifier (OPA) in the 3.10-15.22 MUm range and a Ho:YAG laser-pumped
OPA in the 3.49-5.18 MUm range.
PMID- 28414352
TI - Infrared absorption spectrometer for the determination of temperature and species
profiles in an entrained flow gasifier.
AB - An absorption spectrometer utilizing a tunable distributed feedback diode laser
at 2.3 MUm and an interband cascade laser at 3.1 MUm has been developed to
measure temperature and concentrations of CO, CH4,
C2H2, and H2O under gasification conditions. A
wavelength division multiplexing approach using a single ZrF4-fiber
was used to measure both wavelength regions simultaneously. The performance of
the spectrometer has been tested in laminar flat flames and a heated cell and
then applied for measurements at an atmospheric entrained flow gasifier (REGA). A
water-cooled optical probe was used to provide optical access at two measurement
positions. By moving the burner, axial profiles of temperature and species
concentration could be obtained. These profiles were compared with numerical
simulations and can be used to validate the simulation.
PMID- 28414353
TI - Nonlinear adiabatic optical isolator.
AB - We theoretically propose a method for optical isolation based on adiabatic
nonlinear sum frequency generation in a chirped quasi-phase-matching crystal with
strong absorption at the generated sum frequency wave. The method does not suffer
from the limitations of dynamic reciprocity found in other nonlinear optical
isolation methods and can provide tunable optical isolation with ultrafast all
optical switching capability. Moreover, as an adiabatic technique, it is robust
to variations in the optical design and is relatively broadband.
PMID- 28414354
TI - Dielectric V-ridge gratings: transition from antireflection to retroreflection.
AB - We present a systematic study of the optical properties of dielectric gratings
with symmetric V-shaped ridges having a 90 degree apex angle and refractive index
n. Such structures exhibit completely different optical properties if the
dimensions are scaled with respect to the vacuum wavelength lambda0 of
light. In the subwavelength domain, where the grating period d is less than
lambda0/n, the grating behaves as an antireflection layer. In the
large-period domain d?lambda0 (with normal incidence from the
dielectric side), the grating turns into a micro-retroreflector array. The
transition between these well-known domains is studied using rigorous diffraction
theory. The results are verified experimentally by fabricating and characterizing
V-profile gratings with the aid of wet etching of silicon using a process that
defines a 90 degree apex angle and replication into a polymer.
PMID- 28414355
TI - Experimental study of temporal-spatial binary pattern projection for 3D shape
acquisition.
AB - Three-dimensional (3D) acquisition of an object with modest accuracy and speed is
of particular concern in practice. The performance of digital sinusoidal fringe
pattern projection using an off-the-shelf digital video projector is generally
discounted by the nonlinearity and low switch rate. In this paper, a binary
encoding method to encode one computer-generated standard sinusoidal fringe
pattern is presented for circumventing such deficiencies. In previous work [Opt.
Eng.54, 054108 (2015)OPEGAR0091-328610.1117/1.OE.54.5.054108], we have developed
a 3D system based on this encoding tactic and showed its prospective application.
Here, we first build a physical model to explain the mechanism of how to generate
good sinusoidality. The phase accuracy with respect to the conventional spatial
binary encoding method and sinusoidal fringe pattern is also comparatively
evaluated through simulation and experiments. We also adopt two phase-height
mapping relationships to experimentally compare the measurement accuracy among
them. The results indicate that the proposed binary encoding strategy has a
comparable performance to that of sinusoidal fringe pattern projection and enjoys
advantages over the spatial binary method under the same conditions.
PMID- 28414356
TI - Sensitivity study of x-ray luminescence computed tomography.
AB - X-ray luminescence computed tomography (XLCT) is a hybrid molecular imaging
modality that combines the merits of both x-ray imaging (high resolution) and
optical imaging (high sensitivity). In this study, we have evaluated the
sensitivity of XLCT with phantom experiments by scanning targets of different
phosphor concentrations at different depths. We found that XLCT is capable of
imaging targets of very low concentrations (27.6 MUM or 0.01 mg/mL) at
significant depths, such as 21 mm. Our results demonstrate that there is little
variation in the reconstructed target size with a maximum target size error of
4.35% for different imaging depths for XLCT. We have, we believe for the first
time, compared the sensitivity of XLCT with that of traditional computed
tomography (CT) for phosphor targets. We found that XLCT's use of x-ray-induced
photons provides much higher measurement sensitivity and contrast compared to CT,
which provides image contrast solely based on x-ray attenuation.
PMID- 28414357
TI - Infrared Brewster-angle polarizing beam splitter using a high-index prism with a
small wedge angle.
AB - Specular reflection at the Brewster angle by a planar surface of a high
refractive-index transparent substrate is an effective means of generating
linearly polarized light in the infrared. However, in such a reflection linear
polarizer, the refracted light beam is usually dumped. In this paper we describe
a polarizing beam splitter (PBS) that uses a high-index prism with a small wedge
angle to generate two orthogonally p and s linearly polarized beams that travel
in orthogonal directions. A single-layer antireflection coating (ARC) at the exit
face of the prism can be embedded with aligned Ag nano needles to suppress the
transmission of the small, residual, s-polarized refracted component. An example
of such PBS that uses a PbTe prism with ZnSe ARC in the mid-infrared is
presented.
PMID- 28414358
TI - Optimizing spectral compositions of multichannel LED light sources by IES color
fidelity index and luminous efficacy of radiation: publisher's note.
AB - This note points out additional funding information that was not added to Appl.
Opt.56, 1962 (2017).APOPAI1559-128X10.1364/AO.56.001962.
PMID- 28414359
TI - Optical coherence tomography-integrated, wearable (backpack-type), compact
diagnostic imaging modality for in situ leaf quality assessment: publisher's
note.
AB - This note points out additional funding that was not added to Appl. Opt.56, D108
(2017)APOPAI0003-693510.1364/AO.56.00D108.
PMID- 28414360
TI - Visualizing spatiotemporal pulse propagation: first-order spatiotemporal
couplings in laser pulses.
AB - Even though a general theory of first-order spatiotemporal couplings exists in
the literature, it is often difficult to visualize how these distortions affect
laser pulses. In particular, it is difficult to show the spatiotemporal phase of
pulses in a meaningful way. Here, we propose a general solution to plotting the
electric fields of pulses in three-dimensional space that intuitively shows the
effects of spatiotemporal phases. The temporal phase information is color-coded
using spectrograms and color response functions, and the beam is propagated to
show the spatial phase evolution. Using this plotting technique, we generate two-
and three-dimensional images and movies that show the effects of spatiotemporal
couplings.
PMID- 28414361
TI - Nonimaging polygonal mirrors achieving uniform irradiance distributions on
concentrating photovoltaic cells.
AB - We introduce a design methodology for nonimaging, single-reflection mirrors with
polygonal inlet apertures that generate a uniform irradiance distribution on a
polygonal outlet aperture, enabling a multitude of applications within the domain
of concentrated photovoltaics. Notably, we present single-mirror concentrators of
square and hexagonal perimeter that achieve very high irradiance uniformity on a
square receiver at concentrations ranging from 100 to 1000 suns. These optical
designs can be assembled in compound concentrators with maximized active area
fraction by leveraging tessellation. More advanced multi-mirror concentrators,
where each mirror individually illuminates the whole area of the receiver, allow
for improved performance while permitting greater flexibility for the
concentrator shape and robustness against partial shading of the inlet aperture.
PMID- 28414362
TI - Wideband and multi-frequency infrared cloaking of spherical objects by using the
graphene-based metasurface.
AB - The ultrathin graphene metasurface is proposed as a mantle cloak to achieve
wideband tunable scattering reduction around the spherical (three-dimensional)
objects. The cloaking shell over the metallic or dielectric sphere is structured
by a periodic array of graphene nanodisks that operate at infrared frequencies.
By using the polarizability of the graphene nanodisks and equivalent conductivity
method, the metasurface reactance is obtained. To achieve the cloaking shell for
both dielectric and conducting spheres, the metasurface reactance as a function
of nanodisks dimensions, graphene's Fermi energy, and permittivity of the
surrounding areas can be tuned from the inductive to capacitive situation.
Inhomogeneous metasurfaces including graphene nanodisks with different radii
provide wideband invisibility due to extra resonances. We could significantly
increase the 3-dB bandwidth more than the homogenous case by simpler realistic
designs compared to the multi-layer structures. The analytical results are
confirmed with full-wave numerical simulations.
PMID- 28414363
TI - Signal restoration method for restraining the range walk error of Geiger-mode
avalanche photodiode lidar in acquiring a merged three-dimensional image.
AB - The fluctuation in the number of signal photoelectrons will cause a range walk
error in a Geiger-mode avalanche photodiode (Gm-APD) lidar, which significantly
depends on the target intensity. For a nanosecond-pulsed laser, the range walk
error of traditional time-of-flight will cause deterioration. A new signal
restoration method, based on the Poisson probability response model and the
center-of-mass algorithm, is proposed to restrain the range walk error. We obtain
a high-precision depth and intensity merged 3D image using this method. The range
accuracy is 0.6 cm, and the intensity error is less than 3%.
PMID- 28414364
TI - Experimental analysis of stress fields of rotating structural elements by means
of reflection photoelasticity.
AB - The subject of this paper is an experimental stress analysis of a rotor with a
symmetrical arm end and a rotor with an asymmetrical arm end. The main aim of
this paper is to test the application of the Harmonic Star Method software
developed by the authors. This software analyzes stress states in rotating
structural elements. The stress state of the analyzed rotors is caused by
centrifugal forces. The experiment was carried out by means of reflection
photoelasticity, and the experimental solution was focused on periodical dynamic
effects, which required the use of stroboscopic white light. The resulting
principal normal stresses were compared with stress values, which were obtained
by analytical calculations and by numerical means of the finite element method.
PMID- 28414365
TI - Random phase-shifting algorithm by constructing orthogonal phase-shifting fringe
patterns.
AB - The intensity distribution of fringe patterns becomes nonsinusoidal in real
testing environments. Thus, the performance of existing phase shift extraction
algorithms, which usually compute the desired phase shift by arccosine function
or arcsine function, may be affected. In the presented paper, we report an
arctangent-function-based technique to solve this disturbance. First, two
orthogonal fringe patterns are constructed through subtraction and addition of
two background-removed images. Second, the unequal amplitude between two new
fringe patterns is eliminated using a normalization process. Third, the phase
shift is determined by computing the norms of the two new images. The proposed
method is fast and can be implemented easily in many applications. We verify the
algorithm performance and robustness using both simulated and experimental data,
indicating the high accuracy of the presented method.
PMID- 28414366
TI - Nonlinearity characterization of array spectroradiometers for the solar UV
measurements.
AB - Array spectroradiometers are attractive alternatives to scanning
spectroradiometers in solar ultraviolet measurements. However, the measurement of
solar spectral irradiance imposes stringent requirements for the linearity of the
instruments. In this article, two array spectroradiometers were characterized for
nonlinearity. Significant nonlinearities, in excess of 10%, as a function of
analog-to-digital converter counts were discovered. Additional nonlinearities as
a function of integration time were observed at very long integration times. No
clear residual nonlinearity as a function of spectral irradiance was witnessed
despite the characterization spanning four orders of magnitude of spectral
irradiance. The characterizations were carried out with three measurement setups
that are briefly compared.
PMID- 28414367
TI - Integrated refractive index sensor using silicon slot waveguides.
AB - We propose an integrated refractive index (RI) sensor based on evanescent field
absorption (EFA) within a silicon slot waveguide, where the RI variation is
translated into a varied attenuation coefficient and eventually the output power
at the end of the waveguide. To demonstrate the operating principle of such a RI
EFA sensor, a specific structure is designed and discussed with numerical
simulations. The calculated results indicate that the detection limit of our
proposed RI-EFA sensor could be as good as ~10-8 RIU for homogeneous
sensing and ~10-7 RIU for surface sensing with optimized structural
parameters at a wavelength of 1064 nm. Since only a straight slot waveguide and
optical power detection are required for our proposed sensor, we believe that it
is promising to achieve an integrated and portable sensor on a single chip.
PMID- 28414368
TI - Tunable femtosecond near-IR source by pumping an OPA directly with a 90 MHz
Yb:fiber source.
AB - Up to 400 mW of near-IR (1370-1500 nm) femtosecond pulses are generated from an
optical parametric amplifier directly driven by a Yb:fiber oscillator delivering
100 fs pulses at 1036 nm. The process is seeded by a stable supercontinuum
obtained from a photonic crystal fiber. We use a single pass through a 3 mm,
magnesium oxide-doped, periodically poled LiNbO3 downconversion
crystal to produce a near-IR pulse train with a remarkable power stability of
1.4% (RMS) during one hour. Tuning is achieved by the temperature and the poling
period of the nonlinear crystal.
PMID- 28414369
TI - Frequency comb calibrated frequency-sweeping interferometry for absolute group
refractive index measurement of air.
AB - The absolute group refractive index of air at 194061.02 GHz is measured in real
time using frequency-sweeping interferometry calibrated by an optical frequency
comb. The group refractive index of air is calculated from the calibration peaks
of the laser frequency variation and the interference signal of the two beams
passing through the inner and outer regions of a vacuum cell when the frequency
of a tunable external cavity diode laser is scanned. We continuously measure the
refractive index of air for 2 h, which shows that the difference between measured
results and Ciddor's equation is less than 9.6*10-8, and the standard
deviation of that difference is 5.9*10-8. The relative uncertainty of
the measured refractive index of air is estimated to be 8.6*10-8. The
data update rate is 0.2 Hz, making it applicable under conditions in which air
refractive index fluctuates fast.
PMID- 28414370
TI - Semi-automated localization of dermal epidermal junction in optical coherence
tomography images of skin.
AB - Identifying the location of the dermal epidermal junction (DEJ) in skin images is
essential in several clinical applications of dermatology such as epidermal
thickness determination in healthy versus unhealthy skins, such as basal cell
carcinoma. Optical coherence tomography (OCT) facilitates the visual detection of
DEJ in vivo. However, due to the granular texture of speckle and a low contrast
between dermis and epidermis, a skin border detection method is required for DEJ
localization. Current DEJ algorithms work well for skins with a visible
differentiable epidermal layer but not for the skins of different body sites. In
this paper, we present a semi-automated DEJ localization algorithm based on graph
theory for OCT images of skin. The proposed algorithm is performed in an
interactive framework by a graphical representation of an attenuation coefficient
map through a uniform-cost search method. For border thinning, a fuzzy-based
nonlinear smoothing technique is used. For evaluation, the DEJ detection method
is used by several experts, and the results are compared with manual
segmentation. The mean thickness error between the proposed algorithm and the
experts' opinion in the Bland-Altman plot is computed as 14 MUm; this is
comparable to the resolution of the OCT. The results suggest that the proposed
image processing method successfully detects DEJ.
PMID- 28414371
TI - Flexible global calibration of multiple cameras with nonoverlapping fields of
view using circular targets.
AB - Global calibration of multicamera systems is a difficult problem. The key is to
find an appropriate calibration target. This paper proposes a flexible method to
construct a global calibration target with circular targets. Any object that is
to be measured by the system can be used as a calibration target with the help of
a hand-held scanner. The calibration method does not need a special calibration
target or multiple shots, which makes it flexible in applications. Circular
targets pasted on the calibration target are used as features that are captured
by cameras. The particle swarm optimization method is employed to correct the
eccentricity error in the projection of circular targets. The eccentricity
correction method does not need any prior knowledge except the cameras' intrinsic
parameters. A synthetic data experiment was performed to validate the
eccentricity correction method, and a physical experiment in a train wheelset
inner-side distance measurement system was performed to validate the global
calibration method. The measurement accuracy of the system was better than 0.1
mm, and the eccentricity correction method improved the three-dimensional
reconstruction accuracy by about 0.1 mm.
PMID- 28414372
TI - Graphene-based near-field optical microscopy: high-resolution imaging using
reconfigurable gratings.
AB - High-resolution and fast-paced optical microscopy is a requirement for current
trends in biotechnology and materials industry. The most reliable and adaptable
technique so far to obtain higher resolution than conventional microscopy is near
field scanning optical microscopy (NSOM), which suffers from a slow-paced nature.
Stemming from the principles of diffraction imaging, we present fast-paced
graphene-based scanning-free wide-field optical microscopy that provides image
resolution that competes with NSOM. Instead of spatial scanning of a sharp tip,
we utilize the active reconfigurable nature of graphene's surface conductivity to
vary the diffraction properties of a planar digitized atomically thin graphene
sheet placed in the near field of an object. Scattered light through various
realizations of gratings is collected at the far-field distance and postprocessed
using a transmission function of surface gratings developed on the principles of
rigorous coupled wave analysis. We demonstrate image resolutions of the order of
lambda0/16 using computational measurements through binary graphene
gratings and numerical postprocessing. We also present an optimization scheme
based on the genetic algorithm to predesign the unit cell structure of the
gratings to minimize the complexity of postprocessing methods. We present and
compare the imaging performance and noise tolerance of both grating types. While
the results presented in this article are at terahertz frequencies
(lambda0=10 MUm), where graphene is highly plasmonic, the proposed
microscopy principle can be readily extended to any frequency regime subject to
the availability of tunable materials.
PMID- 28414373
TI - Superlensing microscope objective lens.
AB - Conventional microscope objective lenses are diffraction limited; they cannot
resolve subdiffraction features of a size smaller than 250-300 nm under white
lighting condition. New innovations are required to overcome this limitation. In
this paper, we propose and demonstrate a new superlensing objective lens that
possesses a resolution of 100 nm, which is a two-times resolution improvement
over conventional objectives. This is accomplished by integrating a conventional
microscope objective lens with a superlensing microsphere lens using a customized
lens adaptor. The new objective lens was successfully demonstrated for label-free
super-resolution imaging of 100 nm features in engineering and biological
samples, including a Blu-ray disk sample and adenoviruses. Our work opens a new
door to develop a generic optical superlens, which may transform the field of
optical microscopy and imaging.
PMID- 28414374
TI - Practical dual-band terahertz imaging system.
AB - This paper introduces a dual-band terahertz imaging system as a potential product
for nondestructive testing using heterodyne detectors and continuous-wave
sources. The operating frequencies of the system are 110.4 and 220.8 GHz.
Multiband fusion technology combines the advantages of the greater spatial
resolution of the high-frequency band and the enhanced sensitivity of the low
frequency band to improve the detection ability of the system. Additionally, the
interference cancellation technology is used to obtain a superior image quality.
The spatial resolution of this system was approximately 3 mm. The results show
that the system can be used for bonding quality and embedded defect detection in
radomes and foam materials adhered to metal plates in aircrafts.
PMID- 28414375
TI - Evaluation of femtosecond laser damage to gold pulse compression gratings
fabricated by magnetron sputtering and e-beam evaporation.
AB - In this study, two kinds of Au-coated gratings (ACGs) with a period of 1740
lines/mm were fabricated and evaluated. For these ACG samples, magnetron
sputtering and e-beam evaporation were used as the gold deposition process, and
the samples had a bandwidth of at least 170 nm, with the -1st-order diffraction
efficiency exceeding 90% around the center wavelength of 800 nm. The one-on-one
damage threshold of ACGs fabricated by magnetron sputtering and e-beam
evaporation measured at a pulse width of 60 fs was 0.59 J/cm2 and
0.43 J/cm2 in the case of the beam normal fluence, respectively. The
typical damage morphology of the former type of samples was melting of the gold
film, whereas those of the latter type were blisters and peeling off of the gold
film. In theory, the electromagnetic field, temperature field, and thermal stress
field distribution in the ACGs were calculated using the finite element method.
We demonstrated that the adhesion between the gold film and the photoresist
played an important role in determining the damage behavior. Thus, the laser
resistance of ACG can be improved by enhancing the adhesion between the gold film
and the photoresist, and magnetron sputtering was an alternative method to obtain
ACGs with much better adhesion.
PMID- 28414376
TI - Electromagnetic optimization of the integrated magnetorheological jet polishing
tool and its application in millimeter-scale discontinuous structure processing.
AB - To meet the special demands in small-scale discontinuous optical surface
fabrication, the integrated magnetorheological jet polishing (IMJP) tool with
multiple motion degrees is introduced in this paper. Four jetting models are
implemented and investigated by means of the IMJP tool for practical manufacture.
To ensure steady jetting in a long distance, ideal distribution characteristics
of the magnetic field in the structure is proposed, based on electromagnetic
theory. The magnetic field distribution is simulated subsequently using the
finite element analysis method, and three key parameters in the IMJP tool
structure are optimized through the simulations. The actual magnetic flux density
is measured and spot polishing experiments are conducted in different standoff
distances, verifying the effectiveness of the optimization. A processing
experiment of a millimeter scale structure with milling tool marks located on a
surface with nonuniform curvatures was conducted using the IMJP tool. The
roughness of the polishing region converged to 4.86 nm Ra from a low initial
quality after processing, and the tool marks have been efficiently removed. The
experimental results reveal the reliability of the setup design and the
remarkable roughness convergence ability of the IMJP tool for small complex
structures.
PMID- 28414377
TI - Polarization-based spatial filtering for directional and nondirectional edge
enhancement using an S-waveplate.
AB - Using polarization as an additional parameter apart from amplitude and phase in
spatial filtering experiments offers additional advantages and possibilities. An
S-waveplate that can convert a linearly polarized light into radially or
azimuthally polarized light can also be used for isotropic edge enhancement. For
anisotropic edge enhancement, introduction of a polarizer at the output was
recommended and edge selection was done by orientation of the polarizer. But the
full potential of the S-waveplate as a spatial filter has not been exploited so
far. Unlike the standard amplitude and phase-based Fourier filters, which are
independent to the state of polarization of the illuminating beam, the S
waveplate acts in a different way depending on the state of polarization. The
edge selection does not need to be carried out by changing the orientation of the
polarizer. With a fixed polarizer at the output, we show that either isotropic or
anisotropic edge enhancement in any desired orientation can be performed by
operating the same spatial filter setup in different illuminating polarization
states.
PMID- 28414378
TI - Interference filter tilting to detect a polycyclic aromatic hydrocarbon at the
second harmonic of wavelength modulation frequency.
AB - We present a practical implementation of the wavelength-modulation spectroscopy
technique with second-harmonic detection for selective detection and
concentration measurements of polycyclic aromatic hydrocarbons (PAHs)-common
fossil fuel pollutants. The method is based on excitation light wavelength
modulation around the maximum of a narrow peak in the absorption spectrum of a
PAH and lock-in detection of fluorescence at the second harmonic of the
excitation wavelength modulation frequency. A violet LED is used as the
excitation source and wavelength modulation is performed via narrowband
interference filter tilting. Feasibility is demonstrated with a carcinogenic PAH,
benzo(k)fluoranthene. Model computations are presented to estimate the influence
of the background signal on the sensitivity of the method.
PMID- 28414379
TI - Efficient acousto-optic crystal, TlInS2: acoustic and elastic
anisotropy.
AB - We have studied experimentally the acoustic wave velocities for TlInS2
crystals and determined all components of their elastic stiffness and compliance
tensors. It has been found that TlInS2 reveals small elastic
anisotropy with respect to normal mechanical stresses. The compliance components
S44 and S55 are very large, thus suggesting that the
TlInS2 crystals are extremely compliant to the shear stresses in the
cleavage plane. We have also revealed that the velocities of some of the quasi
transverse waves are very low (~725 m/s), leading to extremely high acousto
optic figures of merit (~2200-9000*10-15 s3/kg). This
implies that the crystals under study can prove to be a very efficient acousto
optic material.
PMID- 28414380
TI - Iterative reconstruction of scene depth with fidelity based on light field data.
AB - Depth reconstruction from the light field, as a depth extracting approach, is a
vibrant research field in computational imaging. In this paper, depth
reconstruction from the light field was approached as an optimization problem by
analyzing the forward and inverse models. The forward and inverse models present
the connection between the light field and the depth of the scene. We proposed an
iterative method for scene depth reconstruction with fidelity from 4D light field
data. The objective function of the optimization problem entails three terms, of
which the matching term is used as the fidelity term, while the gradient term and
classification term constitute the penalty terms. The iterative method minimized
the objective function by correcting mismatching pixels iteratively. In this way,
the reconstruction accuracy of the scene depth was significantly improved with
high robustness, especially in the weak texture and occlusion regions. The
experimental results show that the depth map can be reconstructed with high
accuracy by the iterative method, in alignment with high depth resolution in the
weak texture and occlusion regions. An accurate 3D surface in the field of view
can be achieved using the depth information reconstructed from the 4D light
field.
PMID- 28414381
TI - Interaction between a bubble and a metal target for underwater laser propulsion.
AB - Optical beam deflection and high-speed photographic methods are employed to
investigate the interaction mechanism between a laser-induced bubble and a metal
target for underwater laser propulsion. A preliminary theory is proposed to
reveal the step increases of the kinetic energy transferred to the target during
the process of increasing the incident laser energy. This theory also helps to
explain the increasing coupling efficiency with incident laser energy for
underwater laser propulsion.
PMID- 28414382
TI - Real-time polarization imaging algorithm for camera-based polarization navigation
sensors.
AB - Biologically inspired polarization navigation is a promising approach due to its
autonomous nature, high precision, and robustness. Many researchers have built
point source-based and camera-based polarization navigation prototypes in recent
years. Camera-based prototypes can benefit from their high spatial resolution but
incur a heavy computation load. The pattern recognition algorithm in most
polarization imaging algorithms involves several nonlinear calculations that
impose a significant computation burden. In this paper, the polarization imaging
and pattern recognition algorithms are optimized through reduction to several
linear calculations by exploiting the orthogonality of the Stokes parameters
without affecting precision according to the features of the solar meridian and
the patterns of the polarized skylight. The algorithm contains a pattern
recognition algorithm with a Hough transform as well as orientation measurement
algorithms. The algorithm was loaded and run on a digital signal processing
system to test its computational complexity. The test showed that the running
time decreased to several tens of milliseconds from several thousand
milliseconds. Through simulations and experiments, it was found that the
algorithm can measure orientation without reducing precision. It can hence
satisfy the practical demands of low computational load and high precision for
use in embedded systems.
PMID- 28414383
TI - Design and simulation of reflect-array metasurfaces in the visible regime.
AB - Metasurfaces are new, promising ultrathin materials that can enable many novel
optical devices due to their ability to act as a discontinuity interface that
introduces an abrupt change in amplitude, phase, and sometimes the polarization
of the incident light at the wavelength scale. Therefore they can function as
flat optical elements. Here, we investigate the anomalous reflection of light for
transverse-magnetic (TM) polarization for normal and oblique incidence in the
visible regime. We propose gradient phase gap-surface plasmon metasurfaces that
exhibit high conversion efficiency (up to ~97% of total reflected light) to the
anomalous reflection angle for blue, green, and red wavelengths at normal and
oblique incidence, and where light polarization is unchanged after the
reflection.
PMID- 28414384
TI - Measurement of the linear thermo-optical coefficient of
Ga0.51In0.49P using photonic crystal nanocavities.
AB - Ga0.51In0.49P is a promising candidate for thermally
tunable nanophotonic devices due to its low thermal conductivity. In this work we
study its thermo-optical response. We obtain the linear thermo-optical
coefficient dn/dT=2.0+/-0.3.10-4 K-1 by investigating the
transmission properties of a single mode-gap photonic crystal nanocavity.
PMID- 28414385
TI - Common-path digital holographic microscopy for near-field phase imaging based on
surface plasmon resonance.
AB - We develop a common-path digital holographic microscopy based on prism-coupling
surface plasmon resonance (SPR) for near-field phase imaging. A single beam
splitter with specific configuration is introduced in an SPR imaging system to
realize off-axis holographic recording. By measuring the phase shift difference
of the reflected light at SPR exploiting the proposed holographic microscopy with
high temporal stability, near-field characteristic measurement can be realized.
With its simplicity, vibration isolation, and inherent capability of phase
curvature compensation, the recommended system shows advanced performance in
monitoring tiny refractive index variations and imaging biological tissues.
PMID- 28414386
TI - Detecting phase transitions in a CaCl2-H2O system at low
temperatures using a fiber-optic Fresnel reflection sensor.
AB - Temperature-induced crystallization events in an aqueous calcium chloride
solution in the concentration range of 15-40 mass% are monitored using an optical
fiber Fresnel reflection sensor in the temperature range of 30 degrees C to -200
degrees C. The deviation of the phase boundary from equilibrium and the formation
of an eutectic mixture followed by its densification during rapid cooling are
inferred from the distinct signatures of the optical fiber sensor via the changes
in refractive index. During the natural heating at laboratory ambient conditions,
the optical signals impart the completion of dissolution of ice and
CaCl2.6H2O. The corresponding temperatures have been used
in Linke's equations to obtain the salinities, which are in good agreement with
the intended solution concentrations. The sensor signal imparts simultaneous
melting of the constituents of the eutectic mixture of a 29.7 mass% solution
during the natural heating phase. The persistence of the metastable liquid phase
at -200 degrees C for tens of minutes followed by solidification is observed at
all the concentrations studied. Finally, the feasibility of monitoring phase
transitions in a NaCl-CaCl2-H2O system has been
demonstrated.
PMID- 28414387
TI - Multi-point temperature sensing using a linear-cavity lasing system.
AB - A multi-point fiber sensing system formed from a linear cavity laser is proposed.
Various optical sensing systems have been investigated, for example, using fiber
Bragg grating (FBG) and Brillouin scattering for multi-point sensing. This paper
focuses on a simple sensing system by using multi-wavelength lasing with parallel
cavities and a semiconductor optical amplifier (SOA). First, optical nonlinearity
in amplification of the SOA is discussed to clarify the effects of gain
saturation and four-wave mixing on the proposed multi-channel sensing system. And
then lasing conditions in the linear cavity laser consisting of an SOA, an
arrayed waveguide grating (AWG), and FBGs are theoretically investigated. The
multi-wavelength lasing power is found to be limited mainly by gain saturation in
the SOA. The lasing power for the eight-channel system is evaluated to be -8.5
dBm when the total loss in the linear cavity is 10 dB. The lasing power can be
increased by 3 dB when the channel number is decreased to four. Next, multi
wavelength lasing in the cavity consisting of an SOA, an AWG, a loop mirror, and
fiber mirror reflectors is experimentally demonstrated up to eight channels.
Finally, two-channel temperature sensing ranging from 13 degrees C to 76 degrees
C is experimentally confirmed by using two FBGs as the sensing elements with an
AWG having 100-GHz bandwidth.
PMID- 28414388
TI - Infrared spectroscopy of secondary organic aerosol precursors and investigation
of the hygroscopicity of SOA formed from the OH reaction with guaiacol and
syringol.
AB - Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR)
synchrotron analyses supplemented by density functional theory (DFT) anharmonic
calculations have been undertaken to study the fundamental vibrational signatures
of guaiacol and syringol, two methoxyphenol compounds found at the highest
concentrations in fresh wood smoke and precursors of secondary organic aerosols
(SOA) affecting the radiative balance and chemistry of the atmosphere.
Nitroderivatives of these two compounds have also been studied experimentally for
nitroguaiacol and theoretically for nitrosyringol. All the active fundamental
vibrational bands have been assigned and compared to available gas phase
measurements, providing a vibrational database of the main precursors for the
analysis of SOA produced by atmospheric oxidation of methoxyphenols. In addition,
the SOA formed in an atmospheric simulation chamber from the OH reaction with
guaiacol and syringol were analyzed using the ATR-FTIR synchrotron spectroscopy
and their hygroscopic properties were also investigated. The vibrational study
confirms that nitroguaiacol and nitrosyringol are the main oxidation products of
methoxyphenols by OH and are key intermediates in SOA production. The hydration
experiments highlight the hydrophilic and hydrophobic characters of nitrosyringol
and nitroguaiacol, respectively.
PMID- 28414389
TI - Laser applications to chemical, security, and environmental analysis:
introduction to the feature issue.
AB - This Applied Optics feature issue on laser applications to chemical, security,
and environmental analysis (LACSEA) highlights papers presented at the LACSEA
2016 Fifteenth Topical Meeting sponsored by the Optical Society of America.
PMID- 28414390
TI - Therapeutic monitoring of amiodarone: pharmacokinetics and evaluation of the
relationship between effect and dose/concentration.
AB - Amiodarone is the most effective agent in the therapy of arrhythmias. However,
the clinical effect of acute and chronic treatment is unclear and there are
differences irrespective of comparable plasma/myocardial amiodarone and its
metabolite desethylamiodarone concentations as well. Its unusual pharmacokinetics
results in interindividual variation in plasma levels. The association between
amiodarone and desethylamiodarone plasma levels and clinical efficacy is
difficult to evaluate. This review was carried out to assess whether there is any
objective correlation between amiodarone and desethylamiodarone plasma levels and
the clinical effect. We summarized the results of relevant studies and clarified
the relationship between plasma levels and effect vis a vis the pharmacokinetics
and pharmacogenetics of this drug. Certain correlation was seen with oral
amiodarone therapy, in others, plasma amiodarone levels were unrelated to
therapeutic response and showed no correlation with changes in electrocardiogram
or electrophysiological parametres. Several studies show that plasma
concentration ranging between 0.5 and 2.5 mg/L appears to be the most effective,
others demonstrate no difference between responders and non-responders. One way
of interpreting plasma levels is to establish an individual patient's effective
concentration. Therapeutic drug monitoring can contribute to determining optimal
concentration.
PMID- 28414392
TI - Firearm Injury Prevention: The Role of the Clinician.
AB - More than 2,500 people younger than age 20 years die due to a firearm injury
annually in the United States, and thousands more suffer injuries that are
nonfatal. With nearly one firearm for every American in the US, exposure to a gun
at some point during childhood or adolescence is highly likely. The high number
of fatalities caused by firearms emphasizes the importance of primary prevention.
This article calls on pediatricians to use their advantage as child development
experts to discuss firearm injury prevention in clinical practice via a pragmatic
and nonjudgmental approach. [Pediatr Ann. 2017;46(4):e127-e130.].
PMID- 28414393
TI - Neurological Disorders in Primary Care Pediatrics.
PMID- 28414394
TI - Overview of Sleep and Sleep Disorders in Infancy and Childhood.
AB - Sleep in children is an important and dynamic process, affecting numerous aspects
of health and development. Problems with sleep are relatively common but often
can be challenging to recognize. This article reviews the fundamental aspects of
sleep in children from infancy to adolescence, and the most common and relevant
sleep disorders likely to be encountered in a general pediatric practice. Where
available, current evidence-based recommendations for management are discussed,
including indications for referral to a sleep specialist. [Pediatr Ann.
2017;46(4):e133-e138.].
PMID- 28414395
TI - The Role of Active Recovery and "Rest" After Concussion.
AB - For several years both cognitive and physical rest remained at the forefront in
pediatric postconcussion management. However, the concept of "rest" has not been
well defined and there remains significant variability both in terms of rest
recommendations provided as well as adherence to such recommendations. More
recently, there has been growing evidence to suggest that an earlier return to
light or moderate activity is not detrimental and may, in fact, facilitate
symptomatic improvement, thereby highlighting a new role for active
rehabilitation in recovery from concussion. In this article, we compare historic
recommendations for rest with emerging strategies focused on active
rehabilitation. [Pediatr Ann. 2017;46(4):e139-e144.].
PMID- 28414396
TI - Postural Tachycardia Syndrome: Diagnosis and Management in Adolescents and Young
Adults.
AB - Postural tachycardia syndrome (POTS) represents a common form of orthostatic
intolerance that disproportionately affects young women from puberty through
adulthood. Patients with POTS have day-to-day orthostatic symptoms with the
hallmark feature of an excessive, sustained, and symptomatic rise in heart rate
during orthostatic testing. Although considerable overlap exists, three subtypes
of POTS have been described: neuropathic, hyperadrenergic, and hypovolemic forms.
The wide spectrum of symptoms and comorbidities can make treatment particularly
challenging. Volume expansion with fluid and salt, exercise, and education
constitute a reasonable initial therapy for most patients. Several medicines are
also available to treat orthostatic intolerance and the associated comorbidities.
Defining the POTS subtypes clinically in each patient may help to guide medicine
choices. A multidisciplinary approach to overall management of the patient with
POTS is advised. This review highlights several aspects of POTS with a specific
focus on adolescent and young adult patients. [Pediatr Ann. 2017;46(4):e145
e154.].
PMID- 28414397
TI - Childhood Headache: A Brief Review.
AB - Headaches are common in childhood and adolescence and can cause significant
distress and disability for a child and their family. Providers need to be able
to identify "red flags" for worrisome causes of secondary headaches and recognize
typical primary headache characteristics to provide each patient with the best
possible care to improve their quality of life and minimize disability. This
article reviews the epidemiology of headaches in children, signs and symptoms of
secondary headaches, definitions of some primary childhood headaches, and options
for management of both acute and chronic pediatric migraine. [Pediatr Ann.
2017;46(4):e155-e165.].
PMID- 28414398
TI - Tuberous Sclerosis Complex: A Review.
AB - Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present at
any age and can affect multiple organ systems. This disorder is usually
identified in infants and children based on characteristic skin lesions,
seizures, and cellular overgrowth or hamartomas in the heart, brain, and kidneys.
Tuberous sclerosis complex is a genetic disorder caused by a mutation in either
the TSC1 or TSC2 gene leading to dysfunction of hamartin or tuberin,
respectively. Hamartin and tuberin form a protein complex that helps regulate
cellular hyperplasia. Accurate diagnosis is essential in implementing appropriate
surveillance and treatment to patients with this disorder. Specific guidelines
for diagnosis, surveillance, and management have been proposed by the
International Tuberous Sclerosis Complex Consensus Group. Treatment of tuberous
sclerosis complex is in part symptomatic; however, for certain clinical
manifestations, specific treatments may be indicated. [Pediatr Ann.
2017;46(4):e166-e171.].
PMID- 28414399
TI - Current Understanding of the Health Effects of Electromagnetic Fields.
AB - There has been an exponential increase in the use of electronic devices over the
past few decades. This has led to increased exposure to electromagnetic fields
(EMF). Electric fields result from differences in voltage, whereas magnetic
fields result from the flow of electric current. Higher-frequency waves of EMF
have more energy than lower-frequency waves, and thus generally tend to be more
harmful. An EMF activates cellular stress response and also causes breaks in DNA
strands. There are many methodological barriers to effectively measuring the
associations of EMF and childhood cancers. The consensus from multiple studies is
that there is no causal role of extremely low-frequency EMFs in childhood
cancers, including brain cancer. A recent study showed a link between EMF
radiation and the development of malignant tumors in rats. In light of that
study, the American Academy of Pediatrics set out new recommendations to decrease
the adverse effects of cellphone exposure on children. [Pediatr Ann.
2017;46(4):e172-e174.].
PMID- 28414400
TI - Happy Birthday STFM.
PMID- 28414401
TI - STFM - Two Histories.
PMID- 28414402
TI - Perspectives of an Early Adopter of Family Medicine as a Discipline and a Cause.
PMID- 28414403
TI - STFM - 50 Years of Working to Transform Health Care Through Education.
PMID- 28414404
TI - This Is Why.
PMID- 28414405
TI - A Creation Story.
PMID- 28414406
TI - Residency Training in Family Medicine: A History of Innovation and Program
Support.
AB - BACKGROUND: Residency programs have been integral to the development, expansion
and progression of family medicine as a discipline. Three reports formed the
foundation for graduate medical education in family medicine: Meeting the
Challenge of Family Practice, The Graduate Education of Physicians, and Health is
a Community Affair. In addition, the original core concepts of comprehensiveness,
coordination, continuity, and patient centeredness continue to serve as the
foundation for residency training in family medicine. While the Residency Review
Committee for Family Medicine of the Accreditation Council for Graduate Medical
Education has provided the requirements for training throughout the years, key
organizations including the Society of Teachers of Family Medicine, the American
Academy of Family Physicians, the Association of Family Medicine Residency
Directors, and the American Board of Family Medicine have provided resources for
and supported innovation in programs. Residency Program Solutions, National
Institute for Program Director Development, and Family Medicine Residency
Curriculum Resource are several of the resources developed by these
organizations. The future of family medicine residency training should continue
the emphasis on innovation and development of resources to enhance the training
of residents. Areas for further development include leadership and health care
systems training that allows residents to assume leadership of multidisciplinary
health care teams and increase focus on the family medicine practice population
as the main unit for resident education.
PMID- 28414407
TI - Medical Student Teaching and Recruiting: 50 Years of Balancing Two Educational
Aims.
AB - BACKGROUND: Family medicine (FM) undergraduate medical educators have had two
distinct missions, to increase the knowledge, skills, and attitudes of all
students while also striving to attract students to the field of family medicine.
A five decade literature search was conducted gathering FM curricular innovations
and the parallel trends in FM medical student interest. Student interest in FM
had a rapid first-decade rise to 14%, a second 1990's surge, followed by a drop
to the current plateau of 8-9%. This falls far short of the 30-50% generalist
benchmark needed to fill the country's health care needs. Curricular innovations
fall into three periods: Charismatic Leaders & Clinical Exposures (1965-1978),
Creation of Clerkships of FM (1979-1998) and Curricular Innovations (1998
present). There is good evidence that having a required third-year clerkship
positively impacts student interest in the field, however there is little
research regarding the recruitment impact of specific clerkship curricula. Other
tools associated with student interest include programming geared towards primary
care or rural training and extracurricular opportunities such as FM Interest
Groups. Strategic plans to improve the primary care work force should focus
funding and legislative efforts on effective methods such as: establishing and
maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation. Strategic plans to improve the primary care work force should
focus funding and legislative efforts on effective methods such as: establishing
and maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation. st in FM had a rapid first-decade rise to 14%, a second 1990's
surge, followed by a drop to the current plateau of 8-9%. This falls far short of
the 30-50% generalist benchmark needed to fill the country's healthcare needs.
Curricular innovations fall into three periods: Charismatic Leaders & Clinical
Exposures (1965-1978), Creation of Clerkships of FM (1979-1998) and Curricular
Innovations (1998 - present). There is good evidence that having a required third
year clerkship positively impacts student interest in the field, however there is
little research regarding the recruitment impact of specific clerkship curricula.
Other tools associated with student interest include programming geared towards
primary care or rural training and extracurricular opportunities such as FM
Interest Groups. Strategic plans to improve the primary care work force should
focus funding and legislative efforts on effective methods such as: establishing
and maintaining FM clerkships, admitting students with rural and underserved
backgrounds or primary care interest, developing longitudinal primary care
tracks, and supporting extracurricular FM activities. Rigorous research is needed
to assess how best to utilize limited educational resources to ensure that all
students graduate with a core set of FM competence as well as an increased FM
matriculation.
PMID- 28414408
TI - Family Medicine Research in the United States From the late 1960s Into the
Future.
AB - BACKGROUND: When the new field of family medicine research began a half century
ago, multiple individuals and organizations emphasized that research was a key
mission. Since the field's inception, there have been notable research successes
for which family medicine organizations, researchers, and leaders-assisted by
federal and state governments and private foundations-can take credit. Research
is a requirement for family medicine residency programs but not individual
residents, and multiple family medicine departments offer research training in
various forms for learners at all levels, including research fellowships. Family
physicians have developed practice-based research networks (PBRNs) to conduct
investigations and generate new knowledge. The field of family medicine has seen
the creation of new journals to support the publication of research relevant to
practicing family physicians. Nonetheless, in spite of much growth and many
successes, family physicians and their research have been underrepresented in
research funding. Clinical presentations in family medicine are often complex,
poorly-differentiated, and exist as one of several patient complaints and
diagnoses, and are not well-covered by the narrow basic-science and specialty
research that defines most of the biomedical research enterprise. Overall health
in the United States would benefit from a more robust research participation and
greater support for family medicine research.
PMID- 28414409
TI - Fifty Years of Contributions of Behavioral Science in Family Medicine.
PMID- 28414410
TI - Preparing Family Physicians to Care for Underserved Populations: A Historical
Perspective.
AB - BACKGROUND: Family physicians have been involved in the care of rural and urban
underserved populations since the founding of the specialty. In the early 1970s
family medicine training programs specifically focused on training residents to
work with the underserved were established in both urban and rural settings. Key
to the success of these programs has been a specific focus on improving access to
care, understanding and eliminating health disparities, cultural competency and
behavioral science training that recognizes the challenges often faced by
patients and families living in poor rural and urban areas of the country. In
keeping with a focus on the underserved, several urban underserved residencies
also became national models for the provision of primary care to patients and
families affected by HIV/AIDS. Family medicine training programs focused on the
underserved have resulted in the development of a cohort of family physicians who
care for those most in need in the United States. Despite these achievements,
persistent challenges remain in providing adequate access to care for many living
in rural and inner city settings. New strategies will need to be developed by
family medicine programs and others to better meet these challenges.
PMID- 28414411
TI - Contribution of Osteopathic Training to the Primary Care Workforce.
PMID- 28414412
TI - Response to "Contribution of Osteopathic Training to the Primary Care Workforce".
PMID- 28414413
TI - Medical Student Career Choice: Comparing the Social Accountability of Canadian
and American Medical Schools.
PMID- 28414414
TI - Response to "Medical Student Career Choice: Comparing the Social Accountability
of Canadian and American Medical Schools".
PMID- 28414415
TI - Ultrasonography for confirmation of gastric tube placement.
AB - BACKGROUND: Gastric tubes are commonly used for the administration of drugs and
tube feeding for people who are unable to swallow. Feeding via a tube misplaced
in the trachea can result in severe pneumonia. Therefore, the confirmation of
tube placement in the stomach after tube insertion is important. Recent studies
have reported that ultrasonography provides good diagnostic accuracy estimates in
the confirmation of appropriate tube placement. Hence, ultrasound could provide a
promising alternative to X-rays in the confirmation of tube placement, especially
in settings where X-ray facilities are unavailable or difficult to access.
OBJECTIVES: To assess the diagnostic accuracy of ultrasound for gastric tube
placement confirmation. SEARCH METHODS: We searched the Cochrane Library (2016,
Issue 3), MEDLINE (to March 2016), Embase (to March 2016), National Institute for
Health Research (NIHR) PROSPERO Register (to May 2016), Aggressive Research
Intelligence Facility Databases (to May 2016), ClinicalTrials.gov (to May 2016),
ISRCTN registry (May 2016), World Health Organization International Clinical
Trials Registry Platform (to May 2016) and reference lists of articles, and
contacted study authors. SELECTION CRITERIA: We included studies that evaluated
the diagnostic accuracy of naso- and orogastric tube placement confirmed by
ultrasound visualization using X-ray visualization as the reference standard. We
included cross-sectional studies, and case-control studies. We excluded case
series or case reports. Studies were excluded if X-ray visualization was not the
reference standard or if the tube being placed was a gastrostomy or enteric tube.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk
of bias and extracted data from each of the included studies. We contacted
authors of the included studies to obtain missing data. MAIN RESULTS: We
identified 10 studies (545 participants and 560 tube insertions) which met our
inclusion criteria.No study was assigned low risk of bias or low concern in every
QUADAS-2 domain. We judged only three (30%) studies to have low risk of bias in
the participant selection domain because they performed ultrasound after they
confirmed correct position by other methods.Few data (43 participants) were
available for misplacement detection (specificity) due to the low incidence of
misplacement. We did not perform a meta-analysis because of considerable
heterogeneity of the index test such as the difference of echo window, the
combination of ultrasound with other confirmation methods (e.g. saline flush
visualization by ultrasound) and ultrasound during the insertion of the tube. For
all settings, sensitivity estimates for individual studies ranged from 0.50 to
1.00 and specificity estimates from 0.17 to 1.00. For settings where X-ray was
not readily available and participants underwent gastric tube insertion for
drainage (four studies, 305 participants), sensitivity estimates of ultrasound in
combination with other confirmatory tests ranged from 0.86 to 0.98 and
specificity estimates of 1.00 with wide confidence intervals.For the studies
using ultrasound alone (four studies, 314 participants), sensitivity estimates
ranged from 0.91 to 0.98 and specificity estimates from 0.67 to 1.00. AUTHORS'
CONCLUSIONS: Of 10 studies that assessed the diagnostic accuracy of gastric tube
placement, few studies had a low risk of bias. Based on limited evidence,
ultrasound does not have sufficient accuracy as a single test to confirm gastric
tube placement. However, in settings where X-ray is not readily available,
ultrasound may be useful to detect misplaced gastric tubes. Larger studies are
needed to determine the possibility of adverse events when ultrasound is used to
confirm tube placement.
PMID- 28414416
TI - BUDGET IMPACT ANALYSIS OF USING OMEPRAZOLE IMMEDIATE-RELEASE ORAL SUSPENSION IN
REPLACE OF INTRAVENOUS PANTOPRAZOLE IN CRITICALLY ILL PATIENTS.
AB - OBJECTIVES: The aim of the present study was to estimate the financial
consequence of using omeprazole immediate-release (IR) oral suspension versus
pantoprazole intravenous infusion for preventing stress-related upper
gastrointestinal bleeding in critically ill patients from the perspective of the
health care system. METHODS: An Excel-based model was developed to compare the
cost of prevention of upper gastrointestinal bleeding early after intensive care
admission using the current intravenous (IV) pantoprazole formulation versus
omeprazole IR oral suspension. Total costs included the cost of acid suppressive
drugs and related clinical outcomes. Inputs were obtained from a local clinical
trial, the Ministry of Health database, insurance organizations, hospital and
pharmacy registries, the relevant literature, and expert opinion. The robustness
of the input data was investigated by one-way sensitivity analysis. The model was
developed based on the results of a randomized control trial (RCT), in which
experimental and control groups received omeprazole and pantoprazole,
respectively. RESULTS: According to the proposed model, the cost of
gastrointestinal (GI) bleeding prevention using pantoprazole IV was US$ 950,000
while US$ 750,000 was spent on receiving omeprazole oral suspension. These costs
led to the annual cost-saving of almost US$ 200,000 (US$4 per member, per month)
for the health care system. CONCLUSIONS: In the present study, a budget impact
analysis was performed to assess the financial consequences of using omeprazole
IR oral suspension in place of pantoprazole IV for prevention of upper
gastrointestinal bleeding. The better preventive effect of omeprazole IR oral
suspension when compared with conventional therapy using pantoprazole IV was the
major reason for the final comparative budgetary savings.
PMID- 28414417
TI - Graphene Nanoprobes for Real-Time Monitoring of Isothermal Nucleic Acid
Amplification.
AB - Isothermal amplification is an efficient way to amplify DNA with high accuracy;
however, the real-time monitoring for quantification analysis mostly relied on
expensive and precisely designed probes. In the present study, a graphene oxide
(GO)-based nanoprobe was used to real-time monitor the isothermal amplification
process. The interaction between GO and different DNA structures was
systematically investigated, including single-stranded DNA (ssDNA), double
stranded DNA (dsDNA), DNA 3-helix, and long rolling circle amplification (RCA)
and hybridization chain reaction (HCR) products, which existed in one-, two-, and
three-dimensional structures. It was found that the high rigid structures
exhibited much lower affinity with GO than soft ssDNA, and generally the rigidity
was dependent on the length of targets and the hybridization position with probe
DNA. On the basis of these results, we successfully monitored HCR amplification
process, RCA process, and the enzyme restriction of RCA products with GO
nanoprobe; other applications including the detection of the assembly/disassembly
of DNA 3-helix structures were also performed. Compared to the widely used end
point detection methods, the GO-based sensing platform is simple, sensitive, cost
effective, and especially in a real-time monitoring mode. We believe such studies
can provide comprehensive understandings and evocation on design of GO-based
biosensors for broad application in various fields.
PMID- 28414418
TI - Novel Composite Proton Exchange Membrane with Connected Long-Range Ionic
Nanochannels Constructed via Exfoliated Nafion-Boron Nitride Nanocomposite.
AB - Nafion-boron nitride (NBN) nanocomposites with a Nafion-functionalized periphery
are prepared via a convenient and ecofriendly Nafion-assisted water-phase
exfoliation method. Nafion and the boron nitride nanosheet present strong
interactions in the NBN nanocomposite. Then the NBN nanocomposites were blended
with Nafion to prepare NBN Nafion composite proton exchange membranes (PEMs). NBN
nanocomposites show good dispersibility and have a noticeable impact on the
aggregation structure of the Nafion matrix. Connected long-range ionic
nanochannels containing exaggerated (-SO3-)n ionic clusters are constructed
during the membrane-forming process via the hydrophilic and H-bonding
interactions between NBN nanocomposites and Nafion matrix. The addition of NBN
nanocomposites with sulfonic groups also provides additional proton
transportation spots and enhances the water uptake of the composite PEMs. The
proton conductivity of the NBN Nafion composite PEMs is significantly increased
under various conditions relative to that of recast Nafion. At 80 degrees C-95%
relative humidity, the proton conductivity of 0.5 NBN Nafion is 0.33 S.cm-1, 6
times that of recast Nafion under the same conditions.
PMID- 28414419
TI - Photoswitchable Inhibitor of a Glutamate Transporter.
AB - Excitatory amino acid transporters clear glutamate from the synaptic cleft and
play a critical role in glutamatergic neurotransmission. Their differential roles
in astrocytes, microglia, and neurons are poorly understood due in part to a lack
of pharmacological tools that can be targeted to specific cells and tissues. We
now describe a photoswitchable inhibitor, termed ATT, that interacts with the
major mammalian forebrain transporters EAAT1-3 in a manner that can be reversibly
switched between trans (high-affinity) and cis (low-affinity) configurations
using light of different colors. In the dark, ATT competitively inhibited the
predominant glial transporter EAAT2 with ~200-fold selectivity over the neuronal
transporter EAAT3. Brief exposure to 350 nm light reduced the steady-state
blocker affinity by more than an order of magnitude. Illumination of EAAT2
complexed with ATT induced a corresponding increase in the blocker off-rate
monitored in the presence of glutamate. ATT can be used to reversibly manipulate
glutamate transporter activity with light and may be useful to gain insights into
the dynamic physiological roles of glutamate transporters in the brain, as well
as to study the molecular interactions of transporters with ligands.
PMID- 28414420
TI - Systematic Synthesis and Binding Study of HIV V3 Glycopeptides Reveal the Fine
Epitopes of Several Broadly Neutralizing Antibodies.
AB - A class of new glycan-reactive broadly neutralizing antibodies represented by
PGT121, 10-1074, and PGT128 has recently been discovered that targets specific N
glycans and the peptide region around the V3 domain. However, the glycan
specificity and fine epitopes of these bNAbs remain to be further defined. We
report here a systematic chemoenzymatic synthesis of homogeneous V3 glycopeptides
derived from the HIV-1 JR-FL strain carrying defined N-glycans at N332, N301, and
N295 sites. Antibody binding studies revealed that both the nature and site of
glycosylation in the context of the V3 domain were critical for high-affinity
binding. It was found that antibody PGT128 exhibited specificity for high-mannose
N-glycan with glycosylation site promiscuity, PGT121 showed binding specificity
for glycopeptide carrying a sialylated N-glycan at N301 site, and 10-1074 was
specific for glycopeptide carrying a high-mannose N-glycan at N332 site. The
synthesis and binding studies permit a detailed assessment of the glycan
specificity and the requirement of peptide in the context of antibody-antigen
recognition. The identified glycopeptides can be used as potential templates for
HIV vaccine design.
PMID- 28414421
TI - Shape-Controlled Metal-Free Catalysts: Facet-Sensitive Catalytic Activity Induced
by the Arrangement Pattern of Noncovalent Supramolecular Chains.
AB - Metal-free catalytic materials have recently received broad attention as
promising alternatives to metal-involved catalysts. This is owing to their
inherent capability to overcome the inevitable limitations of metal-involved
catalysts, such as high sensitivity to poisoning, the limited reserves, high cost
and scarcity of metals (especially noble metals), etc. However, the lack of shape
controlled metal-free catalysts with well-defined facets is a formidable
bottleneck limiting our understandings on the underlying structure-activity
relationship at atomic/molecular level, which thereby restrains their rational
design. Here, we report that catalytically active crystals of a porphyrin,
5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, could be shaped into well
defined cubes and sheet-like tetradecahedrons (TDHD), which are exclusively and
predominantly enclosed by {101} and {001} facets, respectively. Fascinatingly,
compared to the cubes, the TDHDs display substantially enhanced catalytic
activity toward water decontamination under visible-light irradiation, although
both the architectures have identical crystalline structure. We disclose that
such interesting shape-sensitive catalytic activity is ascribed to the distinct
spatial separation efficiency of photogenerated electrons and holes induced by
single-channel and multichannel charge transport pathways along noncovalent
supramolecular chains, which are arranged as parallel-aligned and 2D network
patterns, respectively. Our findings provide an ideal scientific platform to
guide the rational design of next-generation metal-free catalysts of desired
catalytic performances.
PMID- 28414422
TI - Synthesis and Structure-Activity Relationships of Tool Compounds Based on
WAY163909, a 5-HT2C Receptor Agonist.
AB - The development of probe molecules that can be used to investigate G protein
coupled receptor (GPCR) pharmacology, trafficking, and relationship with other
GPCRs is an important and growing area of research. Here, we report the synthesis
of analogues of the known selective serotonin (5-HT) 5-HT2C receptor (5-HT2CR)
agonist WAY163909 which were designed to allow for the attachment of a second
ligand, signaling or reporter molecules, as well as immobilization agents to the
parent molecule with the maintenance of agonist activity. This goal was
accomplished by the synthesis of novel molecules in which sites a-d were modified
and resulting compounds were analyzed pharmacologically in vitro.
PMID- 28414423
TI - Robust Fluorine-Free Superhydrophobic Amino-Silicone Oil/SiO2 Modification of
Electrospun Polyacrylonitrile Membranes for Waterproof-Breathable Application.
AB - Superhydrophobic waterproof-breathable membranes have attracted considerable
interest owing to their multifunctional applications in self-cleaning, anti
icing, anticorrosion, outdoor tents, and protective clothing. Despite the
researches pertaning to the construction of superhydrophobic functional membranes
by nanoparticle finishing have increased drastically, the disconnected particle
component is easy to fall off from the membranes under deformation and wear
conditions, which has restricted their wide use in practice. Here, robust
superhydrophobic microporous membranes were prepared via a facile and
environmentally friendly strategy by dip-coating amino-silicone oil (ASO) onto
the electrospun polyacrylonitrile (PAN) membranes, followed by SiO2 nanoparticles
(SiO2 NPs) blade coating. Compared with hydrophilic PAN membranes, the modified
membranes exhibited superhydrophobic surface with an advancing water contact
angle up to 156 degrees , after introducing ASO as low surface energy substance
and SiO2 NPs as filler to reduce the pore size and construct the
multihierarchical rough structure. Varying the concentrations of ASO and SiO2 NPs
systematically, the PAN electrospun membranes modified with 1 wt % ASO and 0.1 wt
% SiO2 NPs were endowed with good water-resistance (74.3 kPa), relative low
thermal conductivity (0.0028 W m-1 K-1), modest vapor permeability (11.4 kg m-2 d
1), and air permeability (20.5 mm s-1). Besides, the inorganic-organic hybrid
coating of ASO/SiO2 NPs could maintain its superhydrophobicity even after 40
abrasion cycles. The resulting membranes were found to resist variations on the
pH scale from 0 to 12, and retained their water repellent properties when exposed
to harsh acidic and alkali conditions. This facile fabrication of durable
fluorine-free superhydrophobic membranes simultaneous with good waterproof
breathable performance provides the advantages for potential applications in self
cleaning materials and versatile protective clothing.
PMID- 28414424
TI - Quantifying the Hierarchical Order in Self-Aligned Carbon Nanotubes from Atomic
to Micrometer Scale.
AB - Fundamental understanding of structure-property relationships in hierarchically
organized nanostructures is crucial for the development of new functionality, yet
quantifying structure across multiple length scales is challenging. In this work,
we used nondestructive X-ray scattering to quantitatively map the multiscale
structure of hierarchically self-organized carbon nanotube (CNT) "forests" across
4 orders of magnitude in length scale, from 2.0 A to 1.5 MUm. Fully resolved
structural features include the graphitic honeycomb lattice and interlayer walls
(atomic), CNT diameter (nano), as well as the greater CNT ensemble (meso) and
large corrugations (micro). Correlating orientational order across hierarchical
levels revealed a cascading decrease as we probed finer structural feature sizes
with enhanced sensitivity to small-scale disorder. Furthermore, we established
qualitative relationships for single-, few-, and multiwall CNT forest
characteristics, showing that multiscale orientational order is directly
correlated with number density spanning 109-1012 cm-2, yet order is inversely
proportional to CNT diameter, number of walls, and atomic defects. Lastly, we
captured and quantified ultralow-q meridional scattering features and built a
phenomenological model of the large-scale CNT forest morphology, which predicted
and confirmed that these features arise due to microscale corrugations along the
vertical forest direction. Providing detailed structural information at multiple
length scales is important for design and synthesis of CNT materials as well as
other hierarchically organized nanostructures.
PMID- 28414425
TI - Tunable UV- and Visible-Light Photoresponse Based on p-ZnO Nanostructures/n
ZnO/Glass Peppered with Au Nanoparticles.
AB - UV- and visible-light photoresponse was achieved via p-type K-doped ZnO nanowires
and nanosheets that were hydrothermally synthesized on an n-ZnO/glass substrate
and peppered with Au nanoparticles. The K content of the p-ZnO nanostructures was
0.36 atom %. The UV- and visible-light photoresponse of the p-ZnO
nanostructures/n-ZnO sample was roughly 2 times higher than that of the ZnO
nanowires. The Au nanoparticles of various densities and diameter sizes were
deposited on the p-ZnO nanostructures/n-ZnO samples by a simple UV photochemical
reaction method yielding a tunable and enhanced UV- and visible-light
photoresponse. The maximum UV and visible photoresponse of the Au nanoparticle
sample was obtained when the diameter size of the Au nanoparticle was
approximately 5-35 nm. On the basis of the localized surface plasmon resonance
effect, the UV, blue, and green photocurrent/dark current ratios of Au
nanoparticle/p-ZnO nanostructures/n-ZnO are ~1165, ~94.6, and ~9.7, respectively.
PMID- 28414426
TI - Two Distinct Assembly States of the Cysteine Regulatory Complex of Salmonella
typhimurium Are Regulated by Enzyme-Substrate Cognate Pairs.
AB - Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS), which
catalyze the last two steps of cysteine biosynthesis, interact and form the
cysteine regulatory complex (CRC). The current model of Salmonella typhimurium
predicts that CRC is composed of one [SAT]hexamer unit and two molecules of
[OASS]dimer. However, it is not clear why [SAT]hexamer cannot engage all of its
six high-affinity binding sites. We examined the assembly state(s) of CRC by size
exclusion chromatography, analytical ultracentrifugation (AUC), isothermal
titration calorimetry (ITC), and surface plasmon resonance (SPR) approaches. We
show that CRC exists in two major assembly states, low-molecular weight (CRC1;
1[SAT]hexamer + 2[OASS]dimer) and high-molecular weight (CRC2; 1[SAT]hexamer +
4[OASS]dimer) states. Along with AUC results, ITC and SPR studies show that
[OASS]dimer binds to [SAT]hexamer in a stepwise manner but the formation of fully
saturated CRC3 (1[SAT]hexamer + 6[OASS]dimer) is not favorable. The fraction of
CRC2 increases as the [OASS]dimer/[SAT]hexamer ratio increases to >4-fold, but
CRC2 can be selectively dissociated into either CRC1 or free enzymes, in the
presence of OAS and sulfide, in a concentration-dependent manner. Together, we
show that CRC is a regulatable multienzyme assembly, sensitive to OASS
substrate(s) levels but subject to negative cooperativity and steric hindrance.
Our results constitute the first report of the dual-assembly-state nature of CRC
and suggest that physiological conditions, which limit sulfate uptake, would
favor CRC1 over CRC2.
PMID- 28414428
TI - Low-Temperature Trapping of Intermediates in the Reaction of NO* with O2.
AB - The autoxidation of NO* was studied in glass-like matrices of 2-methylbutane at
110 K and in a 8:3 v/v mixture of 2,2-dimethylbutane and n-pentane (rigisolve) at
80-90 K, by letting gaseous NO* diffuse into these solvents that were saturated
with O2. In 2-methyllbutane, we observed a red compound. However, in rigisolve at
85-90 K, a bright yellow color appears that turns red when the sample is warmed
by 10-20 K. The new yellow compound is a precursor of the red one and also
diamagnetic. The UV-vis spectrum of the yellow compound contains a band which
resembles that present in ONOO-. Because the red and yellow intermediates are not
paramagnetic, we postulate that O?N-O-O* is in close contact with NO*, or with
another O?N-O-O*. Diffusion of gaseous O2 into rigisolve saturated with NO* does
not produce a color; however, a weak EPR signal (g = 2.010) is observed. This
signal most likely indicates the presence of ONOO*. These findings complement our
earlier observation of a red color at low temperatures and the presence of ONOO*
in the gas phase (Galliker, B.; Kissner, R.; Nauser, T.; Koppenol, W. H. Chem.
Eur. J. 2009, 15, 6161-6168), and they indicate that the termolecular
autoxidation of nitrogen monoxide proceeds via the intermediate ONOO* and not via
N2O2.
PMID- 28414427
TI - Enhancing Extracellular Electron Transfer of Shewanella oneidensis MR-1 through
Coupling Improved Flavin Synthesis and Metal-Reducing Conduit for Pollutant
Degradation.
AB - Dissimilatory metal reducing bacteria (DMRB) are capable of extracellular
electron transfer (EET) to insoluble metal oxides, which are used as external
electron acceptors by DMRB for their anaerobic respiration. The EET process has
important contribution to environmental remediation mineral cycling, and
bioelectrochemical systems. However, the low EET efficiency remains to be one of
the major bottlenecks for its practical applications for pollutant degradation.
In this work, Shewanella oneidensis MR-1, a model DMRB, was used to examine the
feasibility of enhancing the EET and its biodegradation capacity through genetic
engineering. A flavin biosynthesis gene cluster ribD-ribC-ribBA-ribE and metal
reducing conduit biosynthesis gene cluster mtrC-mtrA-mtrB were coexpressed in S.
oneidensis MR-1. Compared to the control strain, the engineered strain was found
to exhibit an improved EET capacity in microbial fuel cells and potentiostat
controlled electrochemical cells, with an increase in maximum current density by
approximate 110% and 87%, respectively. The electrochemical impedance
spectroscopy (EIS) analysis showed that the current increase correlated with the
lower interfacial charge-transfer resistance of the engineered strain. Meanwhile,
a three times more rapid removal rate of methyl orange by the engineered strain
confirmed the improvement of its EET and biodegradation ability. Our results
demonstrate that coupling of improved synthesis of mediators and metal-reducing
conduits could be an efficient strategy to enhance EET in S. oneidensis MR-1,
which is essential to the applications of DMRB for environmental remediation,
wastewater treatment, and bioenergy recovery from wastes.
PMID- 28414429
TI - Sublethal Lead Exposure Alters Movement Behavior in Free-Ranging Golden Eagles.
AB - Lead poisoning of animals due to ingestion of fragments from lead-based
ammunition in carcasses and offal of shot wildlife is acknowledged globally and
raises great concerns about potential behavioral effects leading to increased
mortality risks. Lead levels in blood were correlated with progress of the moose
hunting season. Based on analyses of tracking data, we found that even sublethal
lead concentrations in blood (25 ppb, wet weight), can likely negatively affect
movement behavior (flight height and movement rate) of free-ranging scavenging
Golden Eagles (Aquila chrysaetos). Lead levels in liver of recovered post-mortem
analyzed eagles suggested that sublethal exposure increases the risk of mortality
in eagles. Such adverse effects on animals are probably common worldwide and
across species, where game hunting with lead-based ammunition is widespread. Our
study highlights lead exposure as a considerably more serious threat to wildlife
conservation than previously realized and suggests implementation of bans of lead
ammunition for hunting.
PMID- 28414430
TI - Palladium Catalyzed Asymmetric Three-Component Coupling of Boronic Esters,
Indoles, and Allylic Acetates.
AB - Boronic esters react with 2-lithiated indoles to form boronate intermediates. The
boronate reacts with allylic acetates in the presence of (BINAP)Pd catalysts to
allylate C3 concurrent with alkyl migration from B to C2 of the indole. Overall,
the process is a three-component coupling that joins an allylic acetate, and
indole and an organo-B(pin) species to provide substituted indoles and indolines
with high enantio-, regio-, and diastereoselectivity.
PMID- 28414431
TI - Mononuclear Sulfido-Tungsten(V) Complexes: Completing the Tp*MEXY (M = Mo, W; E =
O, S) Series.
AB - Orange Tp*WSCl2 has been synthesized from the reactions of Tp*WOCl2 with boron
sulfide in refluxing toluene or Tp*WS2Cl with PPh3 in dichloromethane at room
temperature. Mononuclear sulfido-tungsten(V) complexes, Tp*WSXY {X = Y = Cl, OPh,
SPh, SePh; X = Cl, Y = OPh; XY = toluene-3,4-dithiolate (tdt), quinoxaline-2,3
dithiolate (qdt); and Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate} were
prepared by metathesis of Tp*WSCl2 with the respective alkali metal salt of X
/XY2-, or [NHEt3]2(qdt). The complexes were characterized by microanalysis, mass
spectrometry, electrochemistry, and infrared (IR), electron paramagnetic
resonance (EPR) and electronic absorption spectroscopies. The molecular
structures of Tp*WS(OPh)2, Tp*WS(SePh)2, and Tp*WS(tdt) have been determined by X
ray crystallography. The six-coordinate, distorted-octahedral W centers are
coordinated by terminal sulfido (W=S = 2.128(2) - 2.161(1) A), terdentate facial
Tp*, and monodentate/bidentate O/S/Se-donor ligands. The sulfido-W(V) complexes
are characterized by lower energy electronic transitions, smaller giso, and
larger Aiso(183W) values, and more positive reduction potentials compared with
their oxo-W(V) counterparts. This series has been probed by sulfur K-edge X-ray
absorption spectroscopy (XAS), the spectra being assigned by comparison to
Tp*WOXY (X = Y = SPh; XY = tdt, qdt) and time-dependent density functional
theoretical (TD-DFT) calculations. This study provides insight into the
electronic nature and chemistry of the catalytically and biologically important
sulfido-W unit.
PMID- 28414432
TI - Synthetic Transformations Using Molecular Oxygen-Doped Carbon Materials.
AB - Carbon materials like activated carbon (AC) undergo chemisorption with O2 to give
species with electron deficiency in the carbon skeleton and negative charge at
the oxygen end that upon reaction with PPh3 and benzoic acid afford Ph3P?O.
Whereas amine donors react with O2-chemisorbed AC and nucleophiles to give
dehydrogenatively coupled products in 67-89% yields via the corresponding radical
cation and iminium ion intermediates, the reactions using beta-naphthoxide
derivatives give the corresponding oxidatively coupled bi-2-naphthol products in
68-95% yields.
PMID- 28414433
TI - Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed
Carboamination/Cyclopropanation Reactions between N-Enoxyphthalimides and
Alkenes.
AB - Recently, a new synthetic methodology of rhodium-catalyzed
carboamination/cyclopropanation from the same starting materials at different
reaction conditions has been reported. It provides an efficient strategy for the
stereospecific formation of both carbon- and nitrogen-based functionalities
across an alkene. Herein we carried out a detailed theoretical mechanistic
exploration for the reactions to elucidate the switch between carboamination and
cyclopropanation as well as the origin of the chemoselectivity. Instead of the
experimentally proposed RhIII-RhI-RhIII catalytic mechanism, our results reveal
that the RhIII-RhV-RhIII mechanism is much more favorable in the two reactions.
The chemoselectivity is attributed to a combination of electronic and steric
effects in the reductive elimination step. The interactions between alkene and
the rhodacycle during the alkene migration insertion control the
stereoselectivity in the carboamination reactions. The present results disclose a
dual role of the methanol solvent in controlling the chemoselectivity.
PMID- 28414434
TI - Ammonia Activation, H2 Evolution and Nitride Formation from a Molybdenum Complex
with a Chemically and Redox Noninnocent Ligand.
AB - Treatment of the bis(imino)pyridine molybdenum eta6-benzene complex
(iPrPDI)Mo(eta6-C6H6) (iPrPDI, 2,6-(2,6-iPr2C6H3N?CMe)2C5H3N) with NH3 resulted
in coordination induced haptotropic rearrangement of the arene to form
(iPrPDI)Mo(NH3)2(eta2-C6H6). Analogous eta2-ethylene and eta2-cyclohexene
complexes were also synthesized, and the latter was crystallographically
characterized. All three compounds undergo loss of the eta2-coordinated ligand
followed by N-H bond activation, bis(imino)pyridine modification, and H2 loss. A
dual ammonia activation approach has been discovered whereby reversible M-L
cooperativity and coordination induced bond weakening likely contribute to
dihydrogen formation. Significantly, the weakened N-H bonds in
(iPrPDI)Mo(NH3)2(eta2-C2H4) enabled hydrogen atom abstraction and synthesis of a
terminal nitride from coordinated ammonia, a key step in NH3 oxidation.
PMID- 28414436
TI - Pressure-Temperature Phase Diagram Reveals Spin-Lattice Interactions in
Co[N(CN)2]2.
AB - Diamond anvil cell techniques, synchrotron-based infrared and Raman
spectroscopies, and lattice dynamics calculations are combined with prior
magnetic property work to reveal the pressure-temperature phase diagram of
Co[N(CN)2]2. The second-order structural boundaries converge on key areas of
activity involving the spin state exposing how the pressure-induced local lattice
distortions trigger the ferromagnetic -> antiferromagnetic transition in this
quantum material.
PMID- 28414435
TI - Synthesis of BODIPY-Peptide Conjugates for Fluorescence Labeling of EGFR
Overexpressing Cells.
AB - Regioselective functionalization of 2,3,5,6,8-pentachloro-BODIPY 1 produced
unsymmetric BODIPY 5, bearing an isothiocyanate group suitable for conjugation,
in only four steps. The X-ray structure of 5 reveals a nearly planar BODIPY core
with aryl dihedral angles in the range 47.4-62.9 degrees . Conjugation of 5 to
two EGFR-targeting pegylated peptides, 3PEG-LARLLT (6) and 3PEG-GYHWYGYTPQNVI
(7), under mild conditions (30 min at room temperature), afforded BODIPY
conjugates 8 and 9 in 50-80% isolated yields. These conjugates showed red-shifted
absorption and emission spectra compared with 5, in the near-IR region, and were
evaluated as potential fluorescence imaging agents for EGFR overexpressing cells.
SPR and docking investigations suggested that conjugate 8 bearing the LARLLT
sequence binds to EGFR more effectively than 9 bearing the GYHWYGYTPQNVI peptide,
in part due to the lower solubility of 9, and its tendency for aggregation at
concentrations above 10 MUM. Studies in human carcinoma HEp2 cells overexpressing
EGFR demonstrated low dark and photo cytotoxicities for BODIPY 5 and the two
peptide conjugates, and remarkably high cellular uptake for both conjugates 8 and
9, up to 90-fold compared with BODIPY 5 after 1 h. Fluorescence imaging studies
in HEp2 cells revealed subcellular localization of the BODIPY-peptide conjugates
mainly in the Golgi apparatus and the cell lysosomes. The low cytotoxicity of the
new conjugates and their remarkably high uptake into EGFR overexpressing cells
renders them promising imaging agents for cancers overexpressing EGFR.
PMID- 28414437
TI - Phenolic Content and Antioxidant Activity during the Development of 'Brookfield'
and 'Mishima' Apples.
AB - The aim of this study was to characterize the changes in the contents of total
(TPC) and individual (IPC) phenolic compounds, the total antioxidant activity
(TAA) in the peel and pulp, and total anthocyanins (TAN) in the peel during the
development of the fruits of 'Brookfield' and 'Mishima' apple trees. 'Brookfield'
apples were harvested from the 49th to the 138th days after full bloom (DAFB) and
'Mishima' apples from the 45th to the 172th DAFB. In the pulp, the IPC, TPC, and
TAA rapidly reduced at 75 and 79 DAFB for the 'Brookfield' and 'Mishima' apples,
respectively, and then remained constant until commercial maturity. In the peel
of 'Brookfield' apples there was a reduction in the TPC and TAA at 79 DAFB. The
quercetin 3-galactoside, epicatechin, and procyanidin B2 contents reduced up to
107 DAFB with a subsequent increase in the values at commercial maturity. In the
peel of 'Mishima' apples there was a reduction in the TPC, TAA, epicatechin, and
procyanidin B1 and B2 contents at 130 DAFB, with a subsequent increase until
commercial maturity. The TAN content in the peel increased during the 2 and 4
weeks prior to commercial maturity for 'Brookfield' and 'Mishima' apples,
respectively. In the pulp and peel of both cultivars there was a reduction in the
IPC, TPC, and TAA as the development proceeded. On nearing commercial maturity,
there was an increase in the contents of quercetin 3-galactoside, epicatechin,
procyanidin B2, and TAN in the peel for both cultivars.
PMID- 28414438
TI - Custom Coordination Environments for Lanthanoids: Tripodal Ligands Achieve Near
Perfect Octahedral Coordination for Two Dysprosium-Based Molecular Nanomagnets.
AB - Controlling the coordination sphere of lanthanoid complexes is a challenging
critical step toward controlling their relaxation properties. Here we present the
synthesis of hexacoordinated dysprosium single-molecule magnets, where tripodal
ligands achieve a near-perfect octahedral coordination. We perform a complete
experimental and theoretical investigation of their magnetic properties,
including a full single-crystal magnetic anisotropy analysis. The combination of
electrostatic and crystal-field computational tools (SIMPRE and CONDON codes)
allows us to explain the static behavior of these systems in detail.
PMID- 28414439
TI - Mitigation of Thin-Film Composite Membrane Biofouling via Immobilizing Nano-Sized
Biocidal Reservoirs in the Membrane Active Layer.
AB - This work investigates the use of a silver-based metal-organic framework (MOF)
for mitigating biofouling in forward-osmosis thin-film composite (TFC) membranes.
This is the first study of the use of MOFs for biofouling control in membranes.
MOF nanocrystals were immobilized in the active layer of the membranes via
dispersion in the organic solution used for interfacial polymerization. Field
emission scanning electron microscopy (FE-SEM) and X-ray photoelectron
spectroscopy (XPS) characterization results showed the presence of the MOF
nanocrystals in the active layer of the membranes. The immobilization improved
the membrane active layer in terms of hydrophilicity and transport properties
without adversely affecting the selectivity. It imparted antibacterial activity
to the membranes; the number of live bacteria attached to the membrane surface
was over 90% less than that of control membranes. Additionally, the MOF
nanocrystals provided biocidal activity that lasted for 6 months. The
immobilization improved biofouling resistance in the membranes, whose flux had a
decline of 8% after 24 h of operation in biofouling experiments, while that of
the control membranes had a greater decline of ~21%. The better biofouling
resistance is due to simultaneous improvement of antiadhesive and antimicrobial
properties of the membranes. Fluorescence microscopy and FE-SEM indicated
simultaneous improvement in antiadhesive and antimicrobial properties of the TFN
membranes, resulting in limited biofilm formation.
PMID- 28414440
TI - Influence of Active Layer on Separation Potentials of Nanofiltration Membranes
for Inorganic Ions.
AB - Active layers of two fully aromatic and two semi-aromatic nanofiltration
membranes were studied along with surface charge at different electrolyte
composition and effective pore size to elucidate their influence on separation
mechanisms for inorganic ions by steric, charge, and dielectric exclusion. The
membrane potential method used for pore size measurement is underlined as the
most appropriate measurement technique for this application owing to its
dependence on the diffusional potentials of inorganic ions. Crossflow rejection
experiments with dilute feed composition indicate that both fully aromatic
membranes achieved similar rejection despite the differences in surface charge,
which suggests that rejection by these membranes is exclusively dependent on size
exclusion and the contribution of charge exclusion is weak. Rejection experiments
with higher ionic strength and different composition of the feed solution
confirmed this hypothesis. On the other hand, increase in the ionic strength of
feed solution when the charge exclusion effects are negligible due to charge
screening strongly influenced ion rejection by semi-aromatic membranes. The
experimental results confirmed that charge exclusion contributes significantly to
the performance of semi-aromatic membranes in addition to size exclusion. The
contribution of dielectric exclusion to overall ion rejection would be more
significant for fully aromatic membranes.
PMID- 28414441
TI - Suppression of Enteric Bacteria by Bacteriophages: Importance of Phage
Polyvalence in the Presence of Soil Bacteria.
AB - Bacteriophages are widely recognized for their importance in microbial ecology
and bacterial control. However, little is known about how phage polyvalence
(i.e., broad host range) affects bacterial suppression and interspecies
competition in environments harboring enteric pathogens and soil bacteria. Here
we compare the efficacy of polyvalent phage PEf1 versus coliphage T4 in
suppressing a model enteric bacterium (E. coli K-12) in mixtures with soil
bacteria (Pseudomonas putida F1 and Bacillus subtilis 168). Although T4 was more
effective than PEf1 in infecting E. coli K-12 in pure cultures, PEf1 was 20-fold
more effective in suppressing E. coli under simulated multispecies biofilm
conditions because polyvalence enhanced PEf1 propagation in P. putida. In
contrast, soil bacteria do not propagate coliphages and hindered T4 diffusion
through the biofilm. Similar tests were also conducted under planktonic
conditions to discern how interspecies competition contributes to E. coli
suppression without the confounding effects of restricted phage diffusion.
Significant synergistic suppression was observed by the combined effects of
phages plus competing bacteria. T4 was slightly more effective in suppressing E.
coli in these planktonic mixed cultures, even though PEf1 reached higher
concentrations by reproducing also in P. putida (7.2 +/- 0.4 vs 6.0 +/- 1.0
log10PFU/mL). Apparently, enhanced suppression by higher PEf1 propagation was
offset by P. putida lysis, which decreased stress from interspecies competition
relative to incubations with T4. In similar planktonic tests with more competing
soil bacteria species, P. putida lysis was less critical in mitigating
interspecies competition and PEf1 eliminated E. coli faster than T4 (36 vs 42 h).
Overall, this study shows that polyvalent phages can propagate in soil bacteria
and significantly enhance suppression of co-occurring enteric species.
PMID- 28414442
TI - Stolonidiol: Synthesis, Target Identification, and Mechanism for Choline
Acetyltransferase Activation.
AB - Stolonidiol, a marine natural product, has been reported to potentiate the
activity of choline acetyltransferase (ChAT), the enzyme that produces the
neurotransmitter acetylcholine. Here we report the total synthesis of stolonidiol
starting from (R)-(+)-limonene. To identify the mechanism by which ChAT activity
is increased, we sought to identify the biological target of stolonidiol. We show
that stolonidiol binds to the phorbol ester binding site of protein kinase C
(PKC), induces translocation of PKC to the cell membrane, and activates kinase
activity. Furthermore, we confirmed the increase in ChAT activity observed upon
treatment of cells with stolonidiol and show that this effect is mediated by PKC.
Collectively, our data strongly suggest that PKC activation by stolonidiol is
responsible for the resulting potentiation of ChAT activity.
PMID- 28414443
TI - General, Mild, and Metal-Free Synthesis of Phenyl Selenoesters from Anhydrides
and Their Use in Peptide Synthesis.
AB - A mild, practical, and simple procedure for phenyl selenoesters synthesis from
several anhydrides and diphenyl diselenide was developed. This transition-metal
free method provides a straightforward entry to storable Fmoc-amino acid
selenoesters which are effective chemoselective acylating reagents. An
application to oligopeptide synthesis was illustrated.
PMID- 28414444
TI - Accurate Relative Energies and Binding Energies of Large Ice-Liquid Water
Clusters and Periodic Structures.
AB - Relative energies and binding energies are crucial quantities that determine
various molecular properties of ice and water. We developed a new effective
method to compute those energies of bulk ice-liquid water systems. In this work,
ten ice-liquid 144-mers and ten periodic ice-liquid (H2O)64 systems are taken
from the molecular dynamics simulations in the melting process of ice-Ih
crystals. They are investigated at the levels of density functional theory (DFT),
explicitly correlated second-order Moller-Plesset perturbation theory (MP2-F12),
and coupled-cluster singles and doubles with noniterative triples corrections
[CCSD(T)-F12b] in the framework of generalized energy-based fragmentation
approach. Our results show that the changing of noncovalent interactions
significantly influences the performances of DFT and electron correlation methods
for those systems in the melting process of ice. Various DFT methods predict
quite different results for ice and mixed ice-liquid structures but give similar
results for pure liquid ones. It also explains why many DFT-based simulations
lead to inaccurate densities of ice and liquid water. The CCSD(T)-F12b results
suggest that the MP2-F12 method provides satisfactory results and is expected to
be employed to simulate the phase transitions of ice crystal.
PMID- 28414445
TI - Preferential Solvation/Hydration of alpha-Chymotrypsin in Water-Acetonitrile
Mixtures.
AB - The aim of our study is to monitor the preferential hydration/solvation of the
protein macromolecules at low and high water content in water-organic mixtures.
Our approach is based on the analysis of the absolute values of the water/organic
solvent sorption. We applied this approach to estimate the protein
stabilization/destabilization due to the preferential interactions of alpha
chymotrypsin with water-acetonitrile mixtures. At high water content, alpha
chymotrypsin is preferentially hydrated. At the intermediate water content, the
preferential interaction changed from preferential hydration to preferential
binding of acetonitrile. From infrared spectra, changes in the structure of alpha
chymotrypsin were determined through an analysis of the structure of the amide I
band. Acetonitrile augments the intensity of the 1626 cm-1 band assigned to the
intermolecular beta-sheet aggregates. At low water content, the protein is in a
glassy (rigid) state. The H-bond accepting acetonitrile molecules are not
effective in solvating the dehydrated protein molecules alone. Therefore, the
acetonitrile molecules are preferentially excluded from the protein surface,
resulting in the preferential hydration. Advantages of our approach: (i) The
preferential interaction parameters can be determined in the entire range of
water content in water-organic mixtures. (ii) Our approach facilitates the
individual evaluation of the Gibbs energies of water, protein, and organic
solvent.
PMID- 28414446
TI - Radical Decarboxylation/Annulation of Acrylamides with Aliphatic Acyl Peroxides.
AB - A radical decarboxylation/annulation of acrylamides with aliphatic acyl peroxides
was developed, giving a series of linear alkylated oxindoles in moderate to good
yields. The reaction used aliphatic acyl peroxides as the linear alkyl radical
source and tolerated a broad scope of substrates under metal-free conditions,
offering a simple and efficient approach toward alkylated oxindoles.
PMID- 28414447
TI - Supramolecular Porphyrin Photosensitizers: Controllable Disguise and Photoinduced
Activation of Antibacterial Behavior.
AB - A series of supramolecular photosensitizers were fabricated from porphyrin
derivatives (Por) containing quaternary ammonium groups with cucurbit[7]uril
(CB[7]) based on host-guest interactions. The antibacterial activity of Por in
the dark could be turned off upon binding with CB[7], whereas the antibacterial
activity under white-light illumination could be turned on. In addition, its
antibacterial efficiency could be greatly enhanced by introducing metal ions.
When Pd(II) was introduced into porphyrin, its antibacterial efficiency was
enhanced from 40 to 100%. It should be noted that these small molecules showed
little to no cytotoxicity toward mammalian cells even at concentrations higher
than those under the antibacterial condition studied. This line of research will
provide a strategy for germicides consisting of quaternary ammonium groups to
fight against bacterial accumulation in the long term and holds huge potential
for application in the real world.
PMID- 28414449
TI - Time-Dependent pH Scanning of the Acid-Induced Unfolding of Human Serum Albumin
Reveals Stabilization of the Native Form by Palmitic Acid Binding.
AB - The most abundant plasma protein, human serum albumin (HSA), is known to undergo
several conformational transitions in an acidic environment. To avoid buffer
effects and correlate global and local structural changes, we developed a
continuous acidification method and simultaneously monitored the protein changes
by both small-angle scattering (SAXS) and fluorescence. The progressive
acidification, based on the hydrolysis of glucono-delta-lactone from pH 7 to pH
2.5, highlighted a multistep unfolding involving the putative F form (pH 4) and
an extended and flexible conformation (pH < 3.5). The scattering profile of the F
form was extracted by component analysis and further 3D modeled. The effect of
acid unfolding at this intermediate stage was assigned to the rearrangement of
the three albumin domains drifting apart toward a more elongated conformation,
with a partial unfolding of one of the outer domains. To test the stabilizing
effect of fatty acids, here palmitic acid, we compared the acid unfolding process
of albumin with and without ligand. We found that when binding the ligand, the
native conformation was favored up to lower pH values. Our approach solved the
problem of realizing a continuous, homogeneous, and tunable acidification with
simultaneous characterization applicable to study processes triggered by a pH
decrease.
PMID- 28414448
TI - Substrate Profiling and High Resolution Co-complex Crystal Structure of a
Secreted C11 Protease Conserved across Commensal Bacteria.
AB - Cysteine proteases are among the most abundant hydrolytic enzymes produced by
bacteria, and this diverse family of proteins have significant biological roles
in bacterial viability and environmental interactions. Members of the clostripain
like (C11) family of cysteine proteases from commensal gut bacterial strains have
recently been shown to mediate immune responses by inducing neutrophil
phagocytosis and activating bacterial pathogenic toxins. Development of
substrates, inhibitors, and probes that target C11 proteases from enteric
bacteria will help to establish the role of these proteins at the interface of
the host and microbiome in health and disease. We employed a mass spectrometry
based substrate profiling method to identify an optimal peptide substrate of
PmC11, a C11 protease secreted by the commensal bacterium Parabacteroides merdae.
Using this substrate sequence information, we synthesized a panel of fluorogenic
substrates to calculate kcat and KM and to evaluate the importance of the P2
amino acid for substrate turnover. A potent and irreversible tetrapeptide
inhibitor with a C-terminal acyloxymethyl ketone warhead, Ac-VLTK-AOMK, was then
synthesized. We determined the crystal structure of PmC11 in complex with this
inhibitor and uncovered key active-site interactions that govern PmC11 substrate
recognition and specificity. This is the first C11 protease structure in complex
with a substrate mimetic and is also the highest resolution crystal structure of
a C11 protease to date at 1.12 A resolution. Importantly, subjecting human
epithelial cell lysates to PmC11 hydrolysis in combination with subtiligase-based
N-terminal labeling and tandem mass spectrometry proteomics complemented the
stringent substrate specificity observed in the in vitro substrate profiling
experiment. The combination of chemical biological, biophysical, and biochemical
techniques presented here to elucidate and characterize PmC11 substrate
selectivity can be expanded to other proteases and the development of chemical
tools to study these essential proteins in biologically relevant samples, such as
the highly complex distal gut microbiome.
PMID- 28414450
TI - Fabrication of Au-Nanoparticle-Embedded Lipid Bilayer Membranes Supported on
Solid Substrates.
AB - We fabricated gold nanoparticle (Au-NP)-embedded supported lipid bilayers (SLBs)
by two methods. In the vesicle-vesicle fusion method, vesicles with hydrophobized
Au-NPs are ruptured and fused on SiO2/Si substrates. In the vesicle-membrane
fusion method, SLBs without Au-NPs were preformed on the substrate and then
vesicles with Au-NPs were fused into the preformed membranes. In the former
method, Au-NP incorporation into the SLBs was observed as an increase in the
membrane thickness in atomic force microscopy (AFM) images and directly observed
by transmission electron microscopy. In the latter method, fusion of vesicles
into the preformed membranes was confirmed by the fluorescent color change in the
preformed membranes, and Au-NP incorporation was also confirmed by an increase in
the membrane thickness in the AFM images. Key techniques for the successful
vesicle-membrane fusion are hydrophobization of Au-NPs, approach control of
vesicles by mixing the charged lipids, and destabilization of the lipid bilayers
by adding lipids with a small polar headgroup.
PMID- 28414451
TI - Ambient-Light-Promoted Three-Component Annulation: Synthesis of
Perfluoroalkylated Pyrimidines.
AB - An ambient-light-promoted and metal-free three-component reaction of active
methylene compounds, perfluoroalkyl iodides, and guanidines/amidines is reported.
This constitutes a powerful method to prepare perfluoroalkylated pyrimidines with
mild reaction conditions, broad substrate scope, excellent functional group
tolerance, and simple operation. A radical/polar mechanism involving the
formation of a halogen-bond adduct and radical cross-coupling is proposed.
PMID- 28414452
TI - Cation-Exchange Approach to Tuning the Flexibility of a Metal-Organic Framework
for Gated Adsorption.
AB - Achieving tailorable gated adsorption by tuning the dynamic behavior of a host
porous material is of great interest because of its practical application in gas
adsorption and separation. Here we devise a unique cation-exchange approach to
tune the dynamic behavior of a flexible anionic framework, [Zn2(bptc)(datrz)]-
(denoted as MAC-6, where H4bptc = [1,1'-biphenyl]-3,3',5,5'-tetracarboxylic acid
and Hdatrz = 3,5-diamine-1H-1,2,4-triazole), so as to realize the tailorable
gated adsorption. The CO2 adsorption amount at 273 K can be enhanced by
exchanging the counterion of protonated dimethylamine (HDMA+) with
tetraethylammonium (TEA+), tetrabutylammonium (TBA+), and tetramethylammonium
(TMA+), where the adsorption behavior is transferred from nongated to gated
adsorption. Interestingly, the Pgo for gate-opening adsorption can be further
tuned from 442 to 331 mmHg by simply adjusting the ratio of HDMA+ and TMA+. The
origin of this unique tunable property, as revealed by X-ray diffraction
experiments and structure models, is rooted at the cation-responsive
characteristic of this flexible framework.
PMID- 28414453
TI - Global Proteome Profiling of a Marine Copepod and the Mitigating Effect of Ocean
Acidification on Mercury Toxicity after Multigenerational Exposure.
AB - Previously, we found that ocean acidification (OA) mitigates mercury (Hg)
toxicity to marine copepod Tigriopus japonicus under multigenerational exposure
(four generations, F0-F3). To determine the response mechanisms of T. japonicus
against long-term exposure to OA and Hg pollution, we investigated the proteome
of F3 copepods after multigenerational exposure to four conditions: pCO2 400
MUatm + control; pCO2 1000 MUatm + control; pCO2 400 MUatm +1.0 MUg/L Hg; and
pCO2 1000 MUatm +1.0 MUg/L Hg. Functional enrichment analysis indicated that OA
enhanced the copepod's energy production mainly by increasing protein
assimilation and proteolysis as a compensatory strategy, which explained its
physiological resilience to reduced pH. Conversely, Hg treatment decreased many
critical processes, including ferric iron binding, antioxidant activity, cellular
homeostasis, and glutathione metabolism, and these toxic events could translate
into higher-level responses, i.e., restrained reproduction in copepods.
Importantly, the mediation of Hg toxicity in T. japonicus by OA could be
explained by the enhanced lysosome-autophagy pathway proteomes that are
responsible for repairing and removing damaged proteins and enzymes under stress.
Overall, this study provided molecular insights into the response of T. japonicus
to long-term exposure of OA and Hg, with a particular emphasis on the mitigating
impact of the CO2-driven acidification on Hg toxicity.
PMID- 28414454
TI - Novel Proximal Sensing for Monitoring Soil Organic C Stocks and Condition.
AB - Soil information is needed for environmental monitoring to address current
concerns over food, water and energy securities, land degradation, and climate
change. We developed the Soil Condition ANalysis System (SCANS) to help address
these needs. It integrates an automated soil core sensing system (CSS) with
statistical analytics and modeling to characterize soil at fine depth resolutions
and across landscapes. The CSS's sensors include a gamma-ray attenuation
densitometer to measure bulk density, digital cameras to image the measured soil,
and a visible-near-infrared (vis-NIR) spectrometer to measure iron oxides and
clay mineralogy. The spectra are also modeled to estimate total soil organic
carbon (C), particulate, humus, and resistant organic C (POC, HOC, and ROC,
respectively), clay content, cation exchange capacity (CEC), pH, volumetric water
content, available water capacity (AWC), and their uncertainties. Measurements of
bulk density and organic C are combined to estimate C stocks. Kalman smoothing is
used to derive complete soil property profiles with propagated uncertainties. The
SCANS provides rapid, precise, quantitative, and spatially explicit information
about the properties of soil profiles with a level of detail that is difficult to
obtain with other approaches. The information gained effectively deepens our
understanding of soil and calls attention to the central role soil plays in our
environment.
PMID- 28414455
TI - Large-Area CVD-Grown Sub-2 V ReS2 Transistors and Logic Gates.
AB - We demonstrated the fabrication of large-area ReS2 transistors and logic gates
composed of a chemical vapor deposition (CVD)-grown multilayer ReS2 semiconductor
channel and graphene electrodes. Single-layer graphene was used as the
source/drain and coplanar gate electrodes. An ion gel with an ultrahigh
capacitance effectively gated the ReS2 channel at a low voltage, below 2 V,
through a coplanar gate. The contact resistance of the ion gel-gated ReS2
transistors with graphene electrodes decreased dramatically compared with the
SiO2-devices prepared with Cr electrodes. The resulting transistors exhibited
good device performances, including a maximum electron mobility of 0.9 cm2/(V s)
and an on/off current ratio exceeding 104. NMOS logic devices, such as NOT, NAND,
and NOR gates, were assembled using the resulting transistors as a proof of
concept demonstration of the applicability of the devices to complex logic
circuits. The large-area synthesis of ReS2 semiconductors and graphene electrodes
and their applications in logic devices open up new opportunities for realizing
future flexible electronics based on 2D nanomaterials.
PMID- 28414457
TI - Electrochemically Induced Shape-Memory Behavior of Si Nanopillar-Patterned
Electrode for Li Ion Batteries.
AB - A nanopillar-patterned Si substrate was fabricated by photolithography, and its
potential as an anode material for Li ion secondary batteries was investigated.
The Si nanopillar electrode showed a capacity of ~3000 mAh g-1 during 100
charging/discharging cycles, with 98.3% capacity retention, and it was revealed
that the nanopillars underwent delithiation via a process similar to shape-memory
behavior. Despite the tensile stress and structural fractures resulting from
repeated lithiation, the nanoscale size and residual crystalline tip of the
pillar (influenced by the bulk crystalline Si base) enabled recrystallization and
transformation into a single-crystalline phase. To the best of our knowledge,
this observation of shape memory recrystallization mechanism observation was not
reported before for Si used as the active material in Li ion battery
applications; these findings are expected to provide new insights into electrode
materials for rechargeable batteries.
PMID- 28414456
TI - Interfacial Rheology of Sterically Stabilized Colloids at Liquid Interfaces and
Its Effect on the Stability of Pickering Emulsions.
AB - Particle-laden interfaces can be used to stabilize a variety of high-interface
systems, from foams over emulsions to polymer blends. The relation between the
particle interactions, the structure and rheology of the interface, and the
stability of the system remains unclear. In the present work, we experimentally
investigate how micron-sized, near-hard-sphere-like particles affect the
mechanical properties of liquid interfaces. In particular, by comparing dried and
undried samples, we investigate the effect of aggregation state on the properties
of the particle-laden liquid interface and its relation to the stability of the
corresponding Pickering emulsions. Partially aggregated suspensions give rise to
a soft-solid-like response under shear, whereas for stable PMMA particulate
layers a liquid-like behavior is observed. For interfacial creep-recovery
measurements, we present an empirical method to correct for the combined effect
of the subphase drag and the compliance of the double-wall ring geometry, which
makes a significant contribution to the apparent elasticity of weak interfaces.
We further demonstrate that both undried and dried PMMA particles can stabilize
emulsions for months, dispelling the notion that particle aggregation, in bulk or
at the interface, is required to create stable Pickering emulsions. Our results
indicate that shear rheology is a sensitive probe of colloidal interactions but
is not necessarily a predictor of the stability of interfaces, e.g., in quiescent
Pickering emulsions, as in the latter the response to dilatational deformations
can be of prime importance.
PMID- 28414458
TI - Ruthenium(II)-Catalyzed Indolo[2,1-a]isoquinolines Synthesis by Tandem C-H
Allylation and Oxidative Cyclization of 2-Phenylindoles with Allyl Carbonates.
AB - A novel RuII-catalyzed tandem C-H bond activation tool has been successfully
developed involving allylation and oxidative cyclization of 2-phenyl indoles with
allyl carbonates. This one-pot reaction is a new way to synthesize indolo[2,1
a]isoquinoline units via a simple and efficient process.
PMID- 28414459
TI - Highly Anisotropic in-Plane Excitons in Atomically Thin and Bulklike 1T'-ReSe2.
AB - Atomically thin materials such as graphene or MoS2 are of high in-plane symmetry.
Crystals with reduced symmetry hold the promise for novel optoelectronic devices
based on their anisotropy in current flow or light polarization. Here, we present
polarization-resolved optical transmission and photoluminescence spectroscopy of
excitons in 1T'-ReSe2. On reducing the crystal thickness from bulk to a
monolayer, we observe a strong blue shift of the optical band gap from 1.37 to
1.50 eV. The excitons are strongly polarized with dipole vectors along different
crystal directions, which persist from bulk down to monolayer thickness. The
experimental results are well reproduced by ab initio calculations based on the
GW-BSE approach within LDA+GdW approximation. The excitons have high binding
energies of 860 meV for the monolayer and 120 meV for bulk. They are strongly
confined within a single layer even for the bulk crystal. In addition, we find in
our calculations a direct band gap in 1T'-ReSe2 regardless of crystal thickness,
indicating weak interlayer coupling effects on the band gap characteristics. Our
results pave the way for polarization-sensitive applications, such as optical
logic circuits operating in the infrared spectral region.
PMID- 28414460
TI - Analysis of Novel Interactions between Components of the Selenocysteine
Biosynthesis Pathway, SEPHS1, SEPHS2, SEPSECS, and SECp43.
AB - In mammalian cells, the incorporation of the 21st amino acid, selenocysteine,
into proteins is guided by the Sec machinery. The function of this protein
complex requires several protein-protein and protein-RNA interactions, leading to
the incorporation of selenocysteine at UGA codons. It is guided by stem-loop
structures localized in the 3' untranslated regions of the selenoprotein-encoding
genes. Here, we conducted a global analysis of interactions between the Sec
biosynthesis and incorporation components using a bioluminescence resonance
energy transfer assay in mammalian cells that showed that selenocysteine synthase
(SEPSECS), SECp43, and selenophosphate synthetases SEPHS1 and SEPHS2 form
oligomers in eukaryotic cells. We also showed that SEPHS2 interacts with SEPSECS
and SEPHS1; these interactions were confirmed by co-immunoprecipitation. To
further analyze the interactions of SECp43, the protein was expressed in
Escherichia coli, and small-angle X-ray scattering analysis revealed that it is a
globular protein comprising two RNA-binding domains. Using phage display, we
identified potential interaction sites and highlighted two residues (K166 and
P167) required for its dimerization. The SECp43 structural model presented here
constitutes the basis of future exploration of the protein-protein interactions
among early components of the selenocysteine biosynthesis and incorporation
pathway.
PMID- 28414461
TI - A Tetraphenylethene-Naphthyridine-Based AIEgen TPEN with Dual Mechanochromic and
Chemosensing Properties.
AB - Synthesis of new tetraphenylethene (TPE) conjugates via an innocuous route led to
the revelation of a unique TPE-based aggregation-induced emissive fluorogen 3
(TPEN), which showed an interesting mechanochromic property when the emission was
changed from blue to green upon grinding and green to blue upon fuming. The
mechanochromic property of TPEN has been explored to prepare ink-free rewritable
paper for security documentation. A detailed photophysical investigation of the
TPE-naphthyridine scaffold led to the discovery of its high sensitivity to silver
ions (Ag+) over other metal ions with a detection limit of 0.25 MUM in an aqueous
system. The stoichiometry of the complex of TPEN and silver ion was established
to be 2:1 (TPEN:Ag+) on the basis of photophysical studies, mass analysis, and
high-resolution mass spectrometry analysis.
PMID- 28414462
TI - Pyrene-Apelin Conjugation Modulates Fluorophore- and Peptide-Micelle
Interactions.
AB - Bioactive apelin peptide forms ranging in length from 12 to 55 amino acids bind
to and activate the apelin receptor (AR or APJ), a class A G-protein coupled
receptor. Apelin-12, -17, and -36 isoforms, named according to length, with an
additional N-terminal cysteine residue allowed for regiospecific and efficient
conjugation of pyrene maleimide. Through steady-state fluorescence spectroscopy,
the emission properties of pyrene in aqueous buffer were compared to those of the
pyrene-apelin conjugates both without and with zwitterionic or anionic micelles.
Pyrene photophysics are consistent with an expected partitioning into the
hydrophobic micellar cores, while pyrene-apelin conjugation prevented this
partitioning. Apelin, conversely, is expected to preferentially interact with
anionic micelles; pyrene-apelin conjugates appear to lose preferential
interaction. Finally, Forster resonance energy transfer between pyrene and
tryptophan residues in the N-terminal tail and first transmembrane segment (the
AR55 construct, comprising residues 1-55 of the AR) was consistent with efficient
nonspecific pyrene-apelin conjugate binding to micelles rather than direct,
specific apelin-AR55 binding. This approach provides a versatile fluorophore
conjugation strategy for apelin, particularly valuable given that even a highly
hydrophobic fluorophore is not deleterious to peptide behavior in membrane
mimetic micellar systems.
PMID- 28414463
TI - Do Fragments and Crystallization Additives Bind Similarly to Drug-like Ligands?
AB - The success of fragment-based drug design (FBDD) hinges upon the optimization of
low-molecular-weight compounds (MW < 300 Da) with weak binding affinities to lead
compounds with high affinity and selectivity. Usually, structural information
from fragment-protein complexes is used to develop ideas about the binding mode
of similar but drug-like molecules. In this regard, crystallization additives
such as cryoprotectants or buffer components, which are highly abundant in
crystal structures, are frequently ignored. Thus, the aim of this study was to
investigate the information present in protein complexes with fragments as well
as those with additives and how they relate to the binding modes of their drug
like counterparts. We present a thorough analysis of the binding modes of
crystallographic additives, fragments, and drug-like ligands bound to four
diverse targets of wide interest in drug discovery and highly represented in the
Protein Data Bank: cyclin-dependent kinase 2, beta-secretase 1, carbonic
anhydrase 2, and trypsin. We identified a total of 630 unique molecules bound to
the catalytic binding sites, among them 31 additives, 222 fragments, and 377 drug
like ligands. In general, we observed that, independent of the target, protein
fragment interaction patterns are highly similar to those of drug-like ligands
and mostly cover the residues crucial for binding. Crystallographic additives are
also able to show conserved binding modes and recover the residues important for
binding in some of the cases. Moreover, we show evidence that the information
from fragments and drug-like ligands can be applied to rescore docking poses in
order to improve the prediction of binding modes.
PMID- 28414464
TI - Mechanisms of Internalization of Maltose-Modified Poly(propyleneimine)
Glycodendrimers into Leukemic Cell Lines.
AB - Poly(propyleneimine) dendrimers of fourth generation partially modified with
maltose (open shell structure, PPI-m OS) have been proposed as carriers for
nucleotide anticancer drugs. The aim of this work was to provide basic insight
into interactions between fluorescently labeled PPI-m dendrimer and two distinct
leukemia cell models: CCRF-1301 lymphoid cell line and HL-60 myeloid cell line.
We applied qualitative confocal imaging and quantitative flow cytometry, as well
as trypan blue quenching and pharmacological inhibition, to investigate the
course, kinetics, and molecular mechanisms of internalization of nanoparticles.
CCRF-1301 cells take up glycodendrimer macromolecules via a relatively slow,
adsorptive endocytosis process, which is cholesterol-dependent, clathrin- and
caveolin-independent, and not followed by recycling or exocytosis. Morphological
features of this phenomenon point to the involvement of aggregation-induced cell
polarity changes (capping). In HL-60 cells, internalization is very fast,
independent of binding to the cell surface, and proceeds from the fluid phase via
a classical clathrin-dependent mechanism, ending up in an endolysosomal
compartment from which it is not further released. This substantial difference in
internalization rate and mechanism between two cell types has important
repercussions for potential application of this class of glycodendrimers as drug
delivery agents.
PMID- 28414465
TI - Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid
Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose
Tolerance.
AB - The role of the G-protein-coupled bile acid receptor TGR5 in various organs,
tissues, and cell types, specifically in intestinal endocrine L-cells and brown
adipose tissue, has made it a promising therapeutical target in several diseases,
especially type-2 diabetes and metabolic syndrome. However, recent studies have
shown deleterious on-target effects of systemic TGR5 agonists. To avoid these
systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting
enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal
permeability. In this article, we describe their synthesis, characterization, and
biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue,
has low effect on gallbladder volume, and improves glucose homeostasis in a
preclinical murine model of diet-induced obesity and insulin resistance, making
the proof of concept of the potential of topical intestinal TGR5 agonists as
therapeutic agents in type-2 diabetes.
PMID- 28414466
TI - Enantioselective Synthesis of Chiral alpha-Azido and alpha-Aryloxy Quaternary
Stereogenic Centers via the Phase-Transfer-Catalyzed alpha-Alkylation of alpha
Bromomalonates, Followed by SN2 Substitution.
AB - A new efficient synthetic method for chiral alpha-azido-alpha-alkylmalonates and
alpha-aryloxy-alpha-alkylmalonates was developed. The enantioselective alpha
alkylation of diphenylmethyl tert-butyl alpha-bromomalonate under phase-transfer
catalytic conditions [(S,S)-3,4,5-trifluorophenyl-NAS bromide, 50% KOH, toluene,
and -40 degrees C) provided the corresponding alpha-bromo-alpha-alkylmalonates
in high chemical yields (<=98%) and high optical yields (<=99% ee). The resulting
alpha-alkylated products were converted to alpha-azido-alpha-alkylmalonates
(<=96%, <=97% ee) and alpha-aryloxy-alpha-alkylmalonates (<=79%, <=93% ee) by SN2
substitution with sodium azide and aryloxides, respectively.
PMID- 28414467
TI - Variation of Bacterial Communities with Water Quality in an Urban Tropical
Catchment.
AB - A major challenge for assessment of water quality in tropical environments is the
natural occurrence and potential growth of Fecal Indicator Bacteria (FIB). To
gain a better understanding of the relationship between measured levels of FIB
and the distribution of sewage-associated bacteria, including potential
pathogens, in the tropics this study compared the abundance of FIB (Total
coliforms and E. coli) and the Bacteroidales (HF183 marker) with bacterial
community structure determined by next-generation amplicon sequencing. Water was
sampled twice over 6 months from 18 sites within a tropical urban catchment and
reservoir, followed by extraction of DNA from microorganisms, and sequencing
targeting the V3-V4 region of the 16S rRNA gene. Multivariate statistical
analyses indicated that bacterial community composition (BCC) varied between
reservoir and catchment, within catchment land-uses, and with E. coli
concentration. Beta-regression indicated that the proportion of sequences from
sewage-associated taxa (SAT) or pathogen-like sequences (PLS) were predicted most
significantly by measured levels of E. coli(log MPN/100 mL) (chi2 > 8.7; p <
0.003). In addition, SAT were significantly predicted by log HF183 levels
(chi2=13.1; p = 0.0003) while PLS were not. Our study suggests that measurements
of E. coli concentration could be useful in predicting samples enriched in sewage
associated and pathogen-like bacteria in tropical environments despite the
potential for nonconservative behavior.
PMID- 28414469
TI - Correlations between Structure and Near-Infrared Spectra of Saturated and
Unsaturated Carboxylic Acids. Insight from Anharmonic Density Functional Theory
Calculations.
AB - By near-infrared (NIR) spectroscopy and anharmonic density functional theory
(DFT) calculations, we investigate five kinds of saturated and unsaturated
carboxylic acids belonging to the group of short-chain fatty acids: propionic
acid, butyric acid, acrylic acid, crotonic acid, and vinylacetic acid. The
experimental NIR spectra of these five kinds of carboxylic acids are reproduced
by quantum chemical calculations in a broad spectral region of 7500-4000 cm-1 and
for a wide range of concentrations. By employing anharmonic GVPT2 calculations on
DFT level, a detailed interpretation of experimental spectra is achieved,
elucidating structure-spectra correlations of these molecules in the NIR region.
We emphasize the spectral features due to saturated and unsaturated alkyl chains,
the location of a C?C bond within the alkyl chain, and the dimerization of
carboxylic acids. In particular, the existence of a terminal C?C bond leads to
the appearance of highly specific NIR bands. These pronounced bands are located
at wavenumbers where no overlapping with other structure-specific bands occurs,
thus making them good structural markers. Most of the spectral differences
between these two groups of molecules remain subtle, and would be difficult to
reliably ascribe without quantum chemically calculated NIR spectra. Moreover,
anharmonic DFT calculations provide insights on the manifestation of hydrogen
bonding through distinctive spectral features corresponding to cyclic dimers. The
resulting spectral baseline elevation is common for all five investigated
carboxylic acids, and remains consistent with previous results on acetic acid.
PMID- 28414468
TI - 1,3-Dipolar Cycloaddition Reactions of Low-Valent Rhodium and Iridium Complexes
with Arylnitrile N-Oxides.
AB - The reactions between low-valent Rh(I) and Ir(I) metal-carbonyl complexes and
arylnitrile oxides possess the electronic and structural features of 1,3-dipolar
cycloadditions. Density functional theory (DFT) calculations on these reactions,
involving both cyclopentadienyl and carboranyl ligands on the metal carbonyl,
explain the ease of the chemical processes and the stabilities of the resulting
metallaisoxazolin-5-ones. The metal-carbonyl bond has partial double bond
character according to the Wiberg index calculated through NBO analysis, and so
the reaction can be considered a normal 1,3-dipolar cycloaddition involving M?C
bonds. The rates of formation of the metallacycloadducts are controlled by
distortion energy, analogous to their organic counterparts. The superior ability
of anionic Ir complexes to share their electron density and accommodate higher
oxidation states explains their calculated higher reactivity toward
cycloaddition, as compared to Rh analogues.
PMID- 28414470
TI - Association between lateral bias and personality traits in the domestic dog
(Canis familiaris).
AB - Behavioral laterality reflects the cerebral functional asymmetry. Measures of
laterality have been associated with emotional stress, problem-solving, and
personality in some vertebrate species. Thus far, the association between
laterality and personality in the domestic dog has been largely overlooked. In
this study, we investigated whether lateralized (left or right) and ambilateral
dogs differed in their behavioral response to a standardized personality test.
The dog's preferred paw to hold a Kong ball filled with food and the first paw
used to step-off from a standing position were scored as laterality measures. The
Dog Mentality Assessment (DMA) test was used to assess 5 personality traits
(e.g., sociability, aggressiveness) and a broader shy-boldness dimension. No
differences emerged between left- and right-biased dogs on any personality trait.
Instead, ambilateral dogs, scored using the Kong test, scored higher on their
playfulness (Z = -1.98, p = .048) and Aggressiveness (Z = -2.10, p = .036) trait
scores than did lateralized (irrespective of side) dogs. Also, ambilateral dogs
assessed by using the First-Stepping test scored higher than lateralized dogs on
the Sociability (Z = -2.83, p = .005) and Shy-Boldness (Z = -2.34, p = .019)
trait scores. Overall, we found evidence of a link between canine personality and
behavioral laterality, and this was especially true for those traits relating to
stronger emotional reactivity, such as aggressiveness, fearfulness, and
sociability. (PsycINFO Database Record
PMID- 28414471
TI - The reciprocal dynamic model of career decision ambiguity tolerance with career
indecision: A longitudinal three-wave investigation.
AB - The current study investigated the dynamic interplay of career decision ambiguity
tolerance and career indecision over 3 assessment times in a sample of college
students (n = 583). While the previous research has repeatedly shown an
association of career decision ambiguity tolerance with career indecision, the
direction of this association has not been adequately assessed with longitudinal
investigation. It was hypothesized in this study that there is a reciprocal
pattern of career decision ambiguity tolerance leading to subsequent career
indecision and career indecision leading to subsequent career decision ambiguity
tolerance. Using a cross-lagged panel design, this study found support for the
reciprocal pattern that aversion to ambiguity led to increased negative affect
and choice anxiety in career decision making, while negative affect and choice
anxiety led to increased aversion to ambiguity. Additionally, this study revealed
that aversion led to decreased readiness for career decision making and readiness
for career decision making led to increased interests in new information. The key
findings were discussed with respect to the theoretical and clinical implications
for career counseling along with limitations and suggestions for future research.
(PsycINFO Database Record
PMID- 28414472
TI - Disclosing a disability: Do strategy type and onset controllability make a
difference?
AB - In hiring contexts, individuals with concealable disabilities make decisions
about how they should disclose their disability to overcome observers' biases.
Previous research has investigated the effectiveness of binary disclosure
decisions-that is, to disclose or conceal a disability-but we know little about
how, why, or under what conditions different types of disclosure strategies
impact observers' hiring intentions. In this article, we examine disability onset
controllability (i.e., whether the applicant is seen as responsible for their
disability onset) as a boundary condition for how disclosure strategy type
influences the affective reactions (i.e., pity, admiration) that underlie
observers' hiring intentions. Across 2 experiments, we found that when applicants
are seen as responsible for their disability, strategies that de-emphasize the
disability (rather than embrace it) lower observers' hiring intentions by
elevating their pity reactions. Thus, the effectiveness of different types of
disability disclosure strategies differs as a function of onset controllability.
We discuss implications for theory and practice for individuals with disabilities
and organizations. (PsycINFO Database Record
PMID- 28414473
TI - An alter-centric perspective on employee innovation: The importance of alters'
creative self-efficacy and network structure.
AB - While most social network studies of employee innovation behavior examine the
focal employees' ("egos'") network structure, we employ an alter-centric
perspective to study the personal characteristics of employees' network contacts
their "alters"-to better understand employee innovation. Specifically, we examine
how the creative self-efficacy (CSE) and innovation behavior of employees' social
network contacts affects their ability to generate and implement novel ideas.
Hypotheses were tested using a sample of 144 employees in a U.S.-based product
development organization. We find that the average CSE of alters in an employee's
problem solving network is positively related to that employee's innovation
behavior, with this relationship being mediated by these alters' average
innovation behavior. The relationship between the alters' average innovation
behavior and the employee's own innovation behavior is strengthened when these
alters have less dense social networks. Post hoc results suggest that having
network contacts with high levels of CSE also leads to an increase in ego's
personal CSE 1 year later in cases where the employee's initial level of CSE was
relatively low. Implications for theory and practice are discussed. (PsycINFO
Database Record
PMID- 28414474
TI - Abstinence based incentives plus parent training for adolescent alcohol and other
substance misuse.
AB - The purpose of this study was to conduct a randomized test of clinic- and home
based incentives plus parent training for adolescent problem alcohol use.
Adolescents (N = 75) with alcohol misuse, with or without other substance misuse,
were enrolled. All youth received individual Motivational Enhancement
Therapy/Cognitive Behavior Therapy and weekly urine drug testing. The
experimental condition (EXP) included Abstinence Incentives (clinic-based
incentives for abstinence from all substances) plus weekly behavioral parent
training that included a parent-delivered, abstinence-based, substance monitoring
contract. The comparison condition (CONTROL) included Attendance Incentives
(ATTI). All adolescents met DSM-IV criteria for alcohol abuse or dependence or
reported recent binge drinking, and 77% (N = 58) met criteria for a cannabis use
disorder or had recent cannabis use at baseline. Alcohol and cannabis use
outcomes were compared across treatment conditions. A similar percentage of youth
maintained complete alcohol abstinence across the 36-week follow-up in both
conditions. However, among youth not entirely abstinent from alcohol, EXP
resulted in a lower percentage of days using alcohol during the 36 weeks after
the end of treatment than CONTROL. Among youth who also used cannabis at
baseline, results showed similar benefits of EXP on cannabis use days. Combined
individual and family based treatment, plus abstinence based incentives can
reduce substance use days during and after treatment over and above individual
evidence-based psychosocial treatment plus attendance incentives. Future research
should focus on identifying cost-effective components and incentive levels and
delivery via technology to facilitate dissemination. (PsycINFO Database Record
PMID- 28414476
TI - A socio-cultural instrumental approach to emotion regulation: Culture and the
regulation of positive emotions.
AB - We propose a sociocultural instrumental approach to emotion regulation. According
to this approach, cultural differences in the tendency to savor rather than
dampen positive emotions should be more pronounced when people are actively
pursuing goals (i.e., contexts requiring higher cognitive effort) than when they
are not (i.e., contexts requiring lower cognitive efforts), because cultural
beliefs about the utility of positive emotions should become most relevant when
people are engaging in active goal pursuit. Four studies provided support for our
theory. First, European Americans perceived more utility and less harm of
positive emotions than Japanese did (Study 1). Second, European Americans
reported a stronger relative preference for positive emotions than Asians, but
this cultural difference was larger in high cognitive effort contexts than in
moderate or low cognitive effort contexts (Study 2). Third, European Americans
reported trying to savor rather than dampen positive emotions more than Asians
did when preparing to take an exam, a typical high cognitive effort context
(Studies 3-4), but these cultural differences were attenuated when an exam was
not expected (Study 3) and disappeared when participants expected to interact
with a stranger (Study 4). These findings suggest that cultural backgrounds and
situational demands interact to shape how people regulate positive emotions.
(PsycINFO Database Record
PMID- 28414475
TI - Cognitive functioning of adolescent and young adult cannabis users in the
Philadelphia Neurodevelopmental Cohort.
AB - Cannabis use in youth is rising and has been linked to deficits in cognitive
functioning. However, cognitive findings have primarily been based on small
samples of users seeking treatment, and few studies have evaluated cognition in
occasional cannabis users. Here, we examined 4,568 adolescents and young adults
(ages 14-21 years) drawn from the Philadelphia Neurodevelopmental Cohort, a
prospective, population-based study. Participants were classified as cannabis Non
Users (n = 3,401), Occasional Users (twice per week or less; n = 940), or
Frequent Users (>3 times per week; n = 227). Mixed-model analyses examined main
effects of cannabis use and interactions between age and cannabis use on
cognitive functioning. There was a significant interaction between cannabis group
and age such that adolescent (but not young adult) Frequent Users performed worse
than Non-Users on measures of executive control (p = .002). Earlier age of
cannabis use was associated with worse performance in executive control in
Occasional Users (p = .04). Unexpectedly, Occasional Users exhibited better
executive control, memory, and social cognition than Non-Users (ps < .05).
Although mild executive control deficits in adolescent frequent users and a
relation between early cannabis initiation and cognitive performance are
partially consistent with prior research, cognitive deficits were not found in
other hypothesized domains in this community-based sample. Moreover, occasional
cannabis users displayed equivalent or even slightly better executive control,
social-cognitive, and memory abilities compared with nonusers, suggesting complex
relationships between cannabis use and cognition in youth. Longitudinal studies
with community samples are needed to identify variables affecting risk and
resilience to cognitive deficits associated with cannabis. (PsycINFO Database
Record
PMID- 28414477
TI - When ideology meets conflict-related content: Influences on emotion generation
and regulation.
AB - Do rightists and leftists experience information about suffering and harm with
differing emotional intensities, depending on the identity of target depicted? Do
they consequently choose differently how to regulate or cope with these emotions?
Research has identified ideological differences in emotional processes, but it
has yet to identify what types of content lead to ideological differences in
emotional intensity or whether these content-dependent differences relate to
differing preferences for engaging versus disengaging emotion-regulation
strategies. We posited that right-left differences in experienced emotional
intensity would be context-dependent, emerging mostly in response to depictions
of harm to the outgroup, in accordance with the centrality of intergroup
attitudes to ideological self-placement in conflict. Study 1 (N = 83) supported
this hypothesis, with leftists (vs. rightists) experiencing outgroup harm (but
not ingroup harm or conflict-irrelevant harm) with greater emotional intensity.
Study 2 (N = 101), which replicated this finding, additionally examined whether
behavioral differences in regulatory choice consequently emerge mostly regarding
outgroup harm. We tested 2 competing hypotheses as to the nature of these
differences: (a) the intensity hypothesis, positing that leftists (more than
rightists) would regulate their intensified reactions to outgroup harm through
disengagement-distraction (vs. engagement-reappraisal) due to a documented
greater preference for disengaging coping strategies as intensity increases, and
(b) the motivation hypothesis, positing that leftists (more than rightists) would
prefer engagement-reappraisal (vs. disengagement-distraction), consistent with
leftists' documented greater preference for intergroup empathy. Results
exclusively supported the intensity hypothesis, and the significance of both
studies is discussed. (PsycINFO Database Record
PMID- 28414478
TI - Enhancing effects of contingency instructions on fear acquisition and extinction
in anxiety disorders.
AB - Explicit instructions regarding stimulus-threat associations increase acquisition
and extinction of fear in healthy participants. The current study aimed to
investigate the effect of contingency instructions on fear acquisition and
extinction in patients with anxiety disorders. Patients with various anxiety
disorders (N = 104) and healthy comparison participants (N = 93) participated in
a differential fear conditioning task (within-subjects design). Approximately
halfway through the acquisition phase, participants were instructed about the
stimulus-threat association, and approximately halfway through the extinction
phase, participants were informed that the unconditioned stimulus (US) would no
longer be administered. Outcome measures were: fear-potentiated startle, skin
conductance, fearfulness ratings, and US expectancy ratings. Patients
demonstrated overall increased physiological and subjective fear responses during
acquisition and extinction phases, relative to the comparison group. There were
no major differences in fear acquisition and extinction between patients with
different anxiety disorders. During acquisition, instructions led to increased
discrimination of fear responses between a danger cue (conditioned stimulus
[CS]+) and safety cue (CS-) in both patients and comparison participants.
Moreover, instructions strengthened extinction of fear responses in the patient
and comparison group. Patients and healthy comparison participants are better
able to discriminate between danger and safety cues when they have been
explicitly informed about cues that announce a threat situation. Considering the
analogies between fear extinction procedures and exposure therapy, this suggests
that specific instructions on stimulus-threat associations during exposure
therapy might improve short-term treatment efficacy. The question remains for
future studies whether instructions have a positive effect on extinction learning
in the longer term. (PsycINFO Database Record
PMID- 28414479
TI - Group education sessions for women veterans who experienced sexual violence:
Qualitative findings.
AB - INTRODUCTION: The impact of sexual violence (SV) on mental health, self-care, and
interpersonal relationships is profound and poses special challenges to health
care delivery. Reproductive health care merits special attention because the care
required may be linked to reminders of past abuse. We explored facilitators and
barriers affecting the use of reproductive health services among women veterans
with a history of SV. METHOD: Between June and September 2015, we conducted 2
focus groups and 3 general education sessions with 27 female veterans with a
history of SV at 1 medical center. We analyzed transcripts according to applied
thematic analysis and used Nvivo software for data management and retrieval.
RESULTS: Three main themes emerged from the focus groups and education sessions.
PARTICIPANTS: (a) expressed a desire for greater agency in relation to the
control they have over their bodies and medical care; (b) described how
posttraumatic stress symptoms are retriggered during medical care; and (c)
expressed needs for additional education, peer and provider support within the
medical system. DISCUSSION: For women with a history of SV, multiple individual
and systemic barriers complicate how they utilize reproductive health services.
Group education sessions were an effective mode of support, information and
connection to other women within the Veterans Health Administration. (PsycINFO
Database Record
PMID- 28414480
TI - Fungible parameter estimates in structural equation modeling.
AB - Extending work by Waller (2008) on fungible regression coefficients, we propose a
method for computation of fungible parameter estimates in structural equation
modeling. Such estimates are defined as distinct alternative solutions for
parameter estimates, where all fungible solutions yield identical model fit that
is only slightly worse than the fit provided by optimal estimates. When such
alternative estimates are found to be highly discrepant from optimal estimates,
then substantive interpretation based on optimal estimates is called into
question. We present a computational method and 3 illustrations showing the
potential impact of this approach in applied research, and we discuss
implications and issues for further research. (PsycINFO Database Record
PMID- 28414481
TI - Word order denotes relevance differences: The case of conjoined phrases with
lexical gender.
AB - This work explores the order of linguistic references to the two genders (e.g.,
men and women vs. women and men). It argues that a gender is more likely to be
mentioned first when it is perceived to have higher relevance in a context rather
than lower relevance, and audiences assign stronger relevance to a party when the
party is mentioned first rather than second. Studies 1-3 document the current
prevalence of male-first conjoined phrases in the public (but not family) domain
and link the pattern to historical changes in women's public presence over the
20th century. Study 4 shows that contextual relevance cues affect the odds of
first mention, such that people are more likely to refer to a woman before a man,
when the two are in a primary school classroom rather than a corporate office. At
the same time, Studies 4 and 5 find that people often choose to reproduce
collectively preferred word order patterns (e.g., men and women). Studies 6 and 7
show that these choices matter because people assign more relevance to a party
when it comes first rather than second in a conjoined phrase. Overall, this work
offers theoretical grounding and empirical evidence for word order as a means of
expressing and perpetuating gender stereotypes. (PsycINFO Database Record
PMID- 28414482
TI - The power and limits of personal change: When a bad past does (and does not)
inspire in the present.
AB - Observing other people improve their lives can be a powerful source of
inspiration. Eight experiments explore the power, limits, and reasons for this
power of personal change to inspire. We find that people who have improved from
undesirable pasts (e.g., people who used to abuse extreme drugs but no longer do)
are more inspiring than people who maintain consistently desirable standings
(e.g., people who have never used extreme drugs to begin with), because change is
perceived as more effortful than stability (Experiments 1a and 1b). The
inspirational power of personal change is rooted in people's lack of access to
the internal struggles and hard work that many others may endure to successfully
remain 'always-good.' Accordingly, giving observers access into the effort
underlying others' success in maintaining consistently positive standings
restores the inspiring power of being 'always-good' (Experiments 2-4). Finally,
change is more inspiring than stability across many domains but one: people who
used to harm others but have since reformed (e.g., ex-bullies or ex-cheaters) do
not inspire, and in many cases are indeed less inspiring than people who have
never harmed others to begin with (Experiments 5-7). Together, these studies
reveal how, why, and when one's past influences one's present in the eyes of
others: having some "bad" in your past can be surprisingly positive, at least
partly because observers assume that becoming "good" is harder than being "good"
all along. (PsycINFO Database Record
PMID- 28414483
TI - Freedom of racist speech: Ego and expressive threats.
AB - Do claims of "free speech" provide cover for prejudice? We investigate whether
this defense of racist or hate speech serves as a justification for prejudice. In
a series of 8 studies (N = 1,624), we found that explicit racial prejudice is a
reliable predictor of the "free speech defense" of racist expression.
Participants endorsed free speech values for singing racists songs or posting
racist comments on social media; people high in prejudice endorsed free speech
more than people low in prejudice (meta-analytic r = .43). This endorsement was
not principled-high levels of prejudice did not predict endorsement of free
speech values when identical speech was directed at coworkers or the police.
Participants low in explicit racial prejudice actively avoided endorsing free
speech values in racialized conditions compared to nonracial conditions, but
participants high in racial prejudice increased their endorsement of free speech
values in racialized conditions. Three experiments failed to find evidence that
defense of racist speech by the highly prejudiced was based in self-relevant or
self-protective motives. Two experiments found evidence that the free speech
argument protected participants' own freedom to express their attitudes; the
defense of other's racist speech seems motivated more by threats to autonomy than
threats to self-regard. These studies serve as an elaboration of the
Justification-Suppression Model (Crandall & Eshleman, 2003) of prejudice
expression. The justification of racist speech by endorsing fundamental political
values can serve to buffer racial and hate speech from normative disapproval.
(PsycINFO Database Record
PMID- 28414484
TI - Can we "apply" the findings of Forster and Lavie (2008)? On the generalizability
of attentional capture effects under varying levels of perceptual load.
AB - Perceptual Load theory states that the degree of perceptual load on a display
determines the amount of leftover attentional resources that the system can use
to process distracting information. An important corollary of this theory is that
the amount of perceptual load determines the vulnerability of the attention
system to being captured by completely irrelevant stimuli, predicting larger
amounts of capture with low perceptual load than with high perceptual load. This
prediction was first confirmed by Forster and Lavie (2008). Here, we report 6
experiments that followed up on those earlier results, where we find that in many
cases, the opposite pattern is obtained: attentional capture increased with
increasing perceptual load. Given the lack of generalizability of the theory to
new experimental contexts with fairly minor methodological differences, we
conclude that Perceptual Load may not be a useful framework for understanding
attentional capture. The theoretical and applied importance of these findings is
discussed. In particular, we caution against using this theory in applied tasks
and settings because best-use recommendations stemming from this theory regarding
strategies to decrease distractibility may in fact produce the opposite effect:
an increase in distractibility (with distractibility being indexed by the
magnitude of the capture effect). (PsycINFO Database Record
PMID- 28414485
TI - Incentivizing attendance to prolonged exposure for PTSD with opioid use disorder
patients: A randomized controlled trial.
AB - OBJECTIVE: To determine whether contingent monetary incentives increase opioid
use disorder patients' attendance to Prolonged Exposure (PE) therapy and whether
attendance is associated with improvement in posttraumatic stress disorder (PTSD)
and substance use disorder (SUD) outcomes. METHOD: Patients (N = 58) with PTSD
were offered PE or PE with incentives (PE + I; max $480) to attend PE sessions.
Participants were assessed at baseline and weeks 6, 12, and 24 postrandomization.
RESULTS: Participants were mostly women (79%) and Caucasian (71%); mean age 37.43
years (SD = 11.33). PE + I participants attended a median of 9 (of 12) sessions
compared to 1 session for PE participants (p < .001), which included more
exposure sessions (PE + I mdn = 6; PE mdn = 0; p < .001). A Time * treatment
condition interaction indicated that PE + I participants exhibited a greater
decrease in PTSD severity over time than PE participants (OR = 3.1; 95% CI = 0.4
5.7; p = .024). PE + I participants remained in substance use treatment longer
than PE participants (mdn days = 262 vs. 192; p = .039). There were no group
differences in drug use. CONCLUSIONS: Monetary incentives increased SUD patients'
attendance to an otherwise poorly attended treatment for PTSD. Better attendance
in the incentivized group was associated with greater PTSD improvement, better
SUD treatment retention, and no increased drug use. Incentives are well supported
for improving adherence to substance use treatment goals and promising as a means
to improve therapy attendance, which may improve the effectiveness of existing
psychotherapies in difficult-to-treat populations. (PsycINFO Database Record
PMID- 28414486
TI - Girls with childhood ADHD as adults: Cross-domain outcomes by diagnostic
persistence.
AB - OBJECTIVE: To ascertain adult outcomes in 10 domains reflecting symptomatology
(internalizing, externalizing, self-injury, substance use), attainment
(education, employment), and impairment (health, social, driving, overall) as a
function of both childhood diagnosis of attention-deficit/hyperactivity disorder
(ADHD) and persistence of ADHD symptoms across time. METHOD: We prospectively
followed 140 grade-school-aged girls with rigorously diagnosed childhood ADHD and
88 age- and ethnicity-matched comparison girls for 16 years. Outcome measures
were obtained via self- and parent-report questionnaires, interviews, and
objective tests. RESULTS: Childhood ADHD, whether it remitted or persisted, was a
pernicious risk factor for a limited number of poor outcomes, including low
educational attainment, unplanned pregnancy, body mass index (BMI), and clinician
rated impairment. Childhood ADHD that persisted over time, whether completely or
partially, was associated with a number of additional detrimental outcomes in the
externalizing, internalizing, self-injury, occupational, social, and overall
impairment domains. Finally, in this all-female sample, ADHD was not associated
with objective measures of employment, substance use, or driving outcomes.
CONCLUSIONS: We discuss the considerable impairments accruing from both childhood
limited and adult-persisting ADHD, with major implications for the health and
well-being of females with this neurodevelopmental disorder. (PsycINFO Database
Record
PMID- 28414487
TI - How much is enough? Examining frequency criteria for NSSI disorder in adolescent
inpatients.
AB - OBJECTIVE: To empirically evaluate the diagnostic relevance of the proposed
Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; APA, 2013)
Criterion-A frequency threshold for nonsuicidal self-injury (NSSI) disorder.
METHOD: Archival, de-identified, self-reported clinical assessment data from 746
adolescent psychiatric patients (Mage = 14.97; 88% female; 76% White) were used.
The sample was randomly split into 2 unique samples for data analyses. Measures
included assessments of NSSI, proposed DSM-5 NSSI-disorder criteria,
psychopathology, dysfunction, distress, functional impairment, and suicidality.
RESULTS: Discriminant-function analyses run with Sample A identified a
significant differentiation of groups based on a frequency of NSSI at 25 or more
days in the past year, Lambda = .814, chi2(54) = 72.59, p < .05, canonical R2 =
.36. This cutoff was replicated in the second sample. All patients were coded
into 1 of 3 empirically derived NSSI-frequency cutoff groups: high (>25 days),
moderate (5-24 days), and low (1-4 days) and compared. The high-NSSI group scored
higher on most NSSI features, including DSM-5-proposed Criterion-B and -C
symptoms, depression, psychotic symptoms, substance abuse, borderline personality
disorder features, suicidal ideation, and suicide plans, than the moderate- and
low-NSSI groups, who did not differ from each other on many of the variables.
CONCLUSION: The currently proposed DSM-5 Criterion-A frequency threshold for NSSI
disorder lacks validity and clinical utility. The field needs to consider raising
the frequency threshold to ensure that a meaningful and valid set of diagnostic
criteria are established, and to avoid overpathologizing individuals who
infrequently engage in NSSI. (PsycINFO Database Record
PMID- 28414488
TI - An intervention for nonsuicidal self-injury in young adults: A pilot randomized
controlled trial.
AB - OBJECTIVE: Nonsuicidal self-injury (NSSI) is prevalent among young adults and
associated with negative medical and psychological consequences, necessitating
its treatment. However, few treatments have been developed to treat NSSI
specifically, or to treat the behavior among individuals without borderline
personality disorder. The purpose of this study was to investigate the Treatment
for Self-Injurious Behaviors (T-SIB), a brief, behavioral intervention
specifically developed to treat NSSI among young adults, in a pilot randomized
controlled trial (RCT). METHOD: Young adults (N = 33; age: M = 22.36 years, SD =
3.40) meeting inclusion and exclusion criteria were randomly assigned to the
treatment (T-SIB; n = 15) or treatment as usual (n = 18) condition. The sample
was 93.9% female, 42.4% Caucasian, and 30.3% Hispanic/Latino. RESULTS:
Feasibility and acceptability of the study and intervention were supported, and
medium effects were found for decreased NSSI frequency in the T-SIB group using
intent-to-treat analyses. CONCLUSION: Results of this study support the further
evaluation of T-SIB in a larger RCT. (PsycINFO Database Record
PMID- 28414489
TI - Prospective identification of adolescent suicide ideation using classification
tree analysis: Models for community-based screening.
AB - OBJECTIVE: Although a large number of risk markers for suicide ideation have been
identified, little guidance has been provided to prospectively identify
adolescents at risk for suicide ideation within community settings. The current
study addressed this gap in the literature by utilizing classification tree
analysis (CTA) to provide a decision-making model for screening adolescents at
risk for suicide ideation. METHOD: Participants were N = 4,799 youth (Mage =
16.15 years, SD = 1.63) who completed both Waves 1 and 2 of the National
Longitudinal Study of Adolescent to Adult Health. CTA was used to generate a
series of decision rules for identifying adolescents at risk for reporting
suicide ideation at Wave 2. RESULTS: Findings revealed 3 distinct solutions with
varying sensitivity and specificity for identifying adolescents who reported
suicide ideation. Sensitivity of the classification trees ranged from 44.6% to
77.6%. The tree with greatest specificity and lowest sensitivity was based on a
history of suicide ideation. The tree with moderate sensitivity and high
specificity was based on depressive symptoms, suicide attempts or suicide among
family and friends, and social support. The most sensitive but least specific
tree utilized these factors and gender, ethnicity, hours of sleep, school-related
factors, and future orientation. CONCLUSIONS: These classification trees offer
community organizations options for instituting large-scale screenings for
suicide ideation risk depending on the available resources and modality of
services to be provided. This study provides a theoretically and empirically
driven model for prospectively identifying adolescents at risk for suicide
ideation and has implications for preventive interventions among at-risk youth.
(PsycINFO Database Record
PMID- 28414490
TI - Interference and memory capacity limitations.
AB - Working memory (WM) is thought to have a fixed and limited capacity. However, the
origins of these capacity limitations are debated, and generally attributed to
active, attentional processes. Here, we show that the existence of interference
among items in memory mathematically guarantees fixed and limited capacity limits
under very general conditions, irrespective of any processing assumptions.
Assuming that interference (a) increases with the number of interfering items and
(b) brings memory performance to chance levels for large numbers of interfering
items, capacity limits are a simple function of the relative influence of
memorization and interference. In contrast, we show that time-based memory
limitations do not lead to fixed memory capacity limitations that are independent
of the timing properties of an experiment. We show that interference can mimic
both slot-like and continuous resource-like memory limitations, suggesting that
these types of memory performance might not be as different as commonly believed.
We speculate that slot-like WM limitations might arise from crowding-like
phenomena in memory when participants have to retrieve items. Further, based on
earlier research on parallel attention and enumeration, we suggest that crowding
like phenomena might be a common reason for the 3 major cognitive capacity
limitations. As suggested by Miller (1956) and Cowan (2001), these capacity
limitations might arise because of a common reason, even though they likely rely
on distinct processes. (PsycINFO Database Record
PMID- 28414491
TI - Associations between emotional abuse and neglect and dimensions of alexithymia:
The moderating role of sex.
AB - OBJECTIVE: Child maltreatment, specifically emotional maltreatment (i.e., an act,
such as belittling, blaming, or rejection, that is potentially harmful to a
child's emotional development), has emerged as an important correlate of
alexithymia. However, the evidence is mixed with regard to how emotional abuse
and neglect might relate to dimensions of alexithymia (i.e., externally oriented
thinking, difficulty describing feelings, and difficulty identifying feelings).
Furthermore, research is needed to identify individual factors that might
influence these associations. The current study examined the links between
emotional abuse and neglect and externally oriented thinking, difficulty
describing feelings, and difficulty identifying feelings and evaluated whether
sex moderated these associations. METHOD: Participants included 500 emerging
adults (49.6% male) who completed an online battery of questionnaires assessing
history of child maltreatment and dimensions of alexithymia. RESULTS: Regression
analyses revealed that emotional abuse was associated with difficulty describing
feelings and externally oriented thinking, but not difficulty identifying
feelings. Emotional neglect was associated with difficulty identifying feelings,
but not difficulty describing feelings or externally oriented thinking. There
were no sex differences associated with difficulty describing feelings or
externally oriented thinking. However, sex moderated the associations between
emotional abuse and neglect and difficulty identifying feelings such that
emotional abuse and neglect were both more strongly associated with difficulty
identifying feelings for females. CONCLUSION: These results suggest that, in the
aftermath of emotional maltreatment, sex may play an important role in the
development of difficulty identifying feelings. (PsycINFO Database Record
PMID- 28414492
TI - Measuring psychological change after trauma: Psychometric properties of a new bi
directional scale.
AB - OBJECTIVE: The current scientific measures of posttraumatic changes in the wake
of major stressors have mostly been unidirectional. This study is an attempt to
develop a scale that will capture the continuum of positive to negative
psychological changes after trauma. METHOD: Forty-five statements were presented
to a veteran sample (N = 4,053) with the request to report for each item their
experiences of negative, positive, or no posttraumatic changes as a result of
their deployment to Afghanistan. RESULTS: Principal component analysis brought
out 4 dimensions; 26 nonoverlapping items that had correlations above .40 were
selected for the final version of the scale. The 4 dimensions were given the
following designations: Self-Confidence, Interpersonal Involvement, Awareness,
and Social Adaptability. Most veterans reported positive changes (36.8-80.8%)
whereas a minority reported negative changes (4.5-22.0%). The total scale score
correlated negatively with measures of depression, anxiety, sleep disorders, and
posttraumatic stress symptoms. CONCLUSION: The posttraumatic change scale (PTCS)
demonstrated acceptable psychometric properties and captured the range from
negative to positive posttraumatic changes after major stress. Contrary to
several previous studies, positive posttraumatic change, as measured by the PTCS,
was not associated with increased symptoms of psychopathology. This underscores
the heterogeneity of psychological responses to traumatic events. (PsycINFO
Database Record
PMID- 28414493
TI - Predictors of differential PTSD treatment outcomes between veteran and civilian
women after cognitive processing therapy.
AB - OBJECTIVE: This study used data from a recent randomized clinical trial (RCT)
that found differences between women veterans and civilians in posttraumatic
stress disorder (PTSD) treatment response, with civilians demonstrating greater
improvement than did veterans. Despite having similar PTSD severity scores at
baseline, veterans scored roughly 18 points higher than civilians did on the
Clinician-Administered PTSD Scale (CAPS) at posttreatment (p < .01). This study
sought to identify the clinical and treatment variables that were associated with
the differential response to treatment demonstrated by the women in the RCT.
METHOD: Veteran (n = 21) and civilian (n = 105) women with PTSD received
cognitive processing therapy (CPT) for PTSD. These secondary data analyses used
structural equation modeling to investigate the role of 7 clinical and treatment
variables to explain the reduced treatment response to CPT in veterans compared
to civilians. RESULTS: Using structural equation modeling, we found that
differences in CAPS scores at posttreatment were largely mediated by negative
posttraumatic cognitions, as measured by the Posttraumatic Cognition Inventory
(PTCI). Although veterans and civilians had similar PTCI scores at baseline,
civilians had significantly lower PTCI scores at posttreatment, which predicted
lower CAPS scores at posttreatment. This mediation appeared to be at least in
part explained by lower treatment expectancies by veterans compared to civilians.
CONCLUSIONS: Future research should be focused on further understanding and
addressing these 2 treatment outcome predictors in an effort to reduce the gap in
PTSD treatment outcomes between veterans and civilians. (PsycINFO Database Record
PMID- 28414494
TI - Discrimination, daily stress, sleep, and Mexican-origin adolescents'
internalizing symptoms.
AB - OBJECTIVE: Using diary and longitudinal data, the current study examined the
relations between Mexican-origin youths' ethnic discrimination, daily sleep and
stress processes, and internalizing symptoms. METHOD: Adolescents (N = 113; 49.6%
female, Mage = 15.73 years) participated in an initial in-home interview and
reported on ethnic discrimination and internalizing symptoms. They then completed
a 3-day diary study and reported on their daily stress and sleep behaviors (i.e.,
sleep quality, sleep duration). Adolescents' internalizing symptoms were
reassessed 2 years after the initial assessment. RESULTS: Discrimination related
to greater daily stress and lower sleep quality. Daily stress was, in turn,
marginally related to concurrent internalizing symptoms, but not longitudinal
changes in symptoms. Sleep duration was unrelated to discrimination experiences
and concurrent and long-term internalizing symptoms. CONCLUSION: Discrimination
disrupts daily processes that include overall stress levels and sleep quality.
Daily stress processes may help explain the link between discrimination and
Mexican-origin adolescents' concurrent internalizing symptoms. Research examining
daily processes provides insight into psychological and behavioral implications
of discrimination experiences of adolescents. (PsycINFO Database Record
PMID- 28414495
TI - Racial discrimination, racial identity, and impostor phenomenon: A profile
approach.
AB - OBJECTIVES: This study examined the association between racial discrimination and
the impostor phenomenon (IP) and the moderating influence of racial identity on
this relationship. METHOD: One hundred fifty-seven African American college
students (68% female; mean age = 18.63) completed measures of racial
discrimination, racial identity, and IP during 2 waves of data collection.
RESULTS: Utilizing latent profile analyses, 4 patterns of racial identity were
identified: Undifferentiated, Multiculturalist, Race-Focused, and Humanist.
Racial discrimination predicted higher subsequent levels of IP. Racial identity
did not moderate the impact of racial discrimination; however, students in the
Multiculturalist and Humanist groups reported the lowest and highest levels of IP
at Wave 2, respectively. CONCLUSION: IP is influenced by racial discrimination
experiences as well as by the significance and meaning that individuals ascribe
to being African American. (PsycINFO Database Record
PMID- 28414496
TI - Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol
(LAAM) concentrations in opioid-substitution patients.
AB - Tolerance to the psychomotor impairing effects of opioid drugs is expected to
develop with repeated dosing, but may be incomplete. The relationship between
plasma opioid concentration and psychomotor function in opioid-dependent patients
was examined to determine whether impairment was more likely at the time of
highest plasma drug concentration. Sixteen patients participating in a cross-over
trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times
over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood
was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor
LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making
Test were administered at the time of peak plasma concentration. Ten healthy
controls (HCs) also participated. OSPAT scores (obtained for 15 patients)
fluctuated significantly across the dosing-interval for both drugs and were lower
in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1
hr: (mean difference; 95% CI) (2.13; 0.18-4.08); 2 hrs: (2.38; 0.48-4.28)
postdosing) and LAAM (2 hrs: (1.81; 0.09-3.53), and 4 hrs (1.90: 0.9-3.71)
postdosing). Within-participant analysis of the peak-change from baseline for
OSPAT scores found that 10 of the 15 patients could be categorized as impaired on
methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the
DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some
patients receiving opioids long term may exhibit impairment at the time of
highest plasma drug concentration. These patients should be made aware that their
ability to undertake complex tasks may be affected. (PsycINFO Database Record
PMID- 28414498
TI - Neighing, barking, and drumming horses-object related sounds help and hinder
picture naming.
AB - The study presented here investigated how environmental sounds influence picture
naming. In a series of four experiments participants named pictures (e.g., the
picture of a horse) while hearing task-irrelevant sounds (e.g., neighing,
barking, or drumming). Experiments 1 and 2 established two findings, facilitation
from congruent sounds (e.g., picture: horse, sound: neighing) and interference
from semantically related sounds (e.g., sound: barking), both relative to
unrelated sounds (e.g., sound: drumming). Experiment 3 replicated the effects in
a situation in which participants were not familiarized with the sounds prior to
the experiment. Experiment 4 replicated the congruency facilitation effect, but
showed that semantic interference was not obtained with distractor sounds which
were not associated with target pictures (i.e., were not part of the response
set). The general pattern of facilitation from congruent sound distractors and
interference from semantically related sound distractors resembles the pattern
commonly observed with distractor words. This parallelism suggests that the
underlying processes are not specific to either distractor words or distractor
sounds but instead reflect general aspects of semantic-lexical selection in
language production. The results indicate that language production theories need
to include a competitive selection mechanism at either the lexical processing
stage, or the prelexical processing stage, or both. (PsycINFO Database Record
PMID- 28414497
TI - Dual tasking in Parkinson's disease: Cognitive consequences while walking.
AB - OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) and
exacerbate the functional limitations imposed by PD's hallmark motor symptoms,
including impairments in walking. Though much research has addressed the effect
of dual cognitive-locomotor tasks on walking, less is known about their effect on
cognition. The purpose of this study was to investigate the relation between gait
and executive function, with the hypothesis that dual tasking would exacerbate
cognitive vulnerabilities in PD as well as being associated with gait
disturbances. METHOD: Nineteen individuals with mild-moderate PD without dementia
and 13 age- and education-matched normal control adults (NC) participated.
Executive function (set-shifting) and walking were assessed singly and during
dual tasking. RESULTS: Dual tasking had a significant effect on cognition
(reduced set-shifting) and on walking (speed, stride length) for both PD and NC,
and also on stride frequency for PD only. The impact of dual tasking on walking
speed and stride frequency was significantly greater for PD than NC. Though the
group by condition interaction was not significant, PD had fewer set-shifts than
NC on dual task. Further, relative to NC, PD showed significantly greater
variability in cognitive performance under dual tasking, whereas variability in
motor performance remained unaffected by dual tasking. CONCLUSIONS: Dual tasking
had a significantly greater effect in PD than in NC on cognition as well as on
walking. The results suggest that assessment and treatment of PD should consider
the cognitive as well as the gait components of PD-related deficits under dual
task conditions. (PsycINFO Database Record
PMID- 28414499
TI - Executive and perceptual distraction in visual working memory.
AB - The contents of visual working memory are likely to reflect the influence of both
executive control resources and information present in the environment. We
investigated whether executive attention is critical in the ability to exclude
unwanted stimuli by introducing concurrent potentially distracting irrelevant
items to a visual working memory paradigm, and manipulating executive load using
simple or more demanding secondary verbal tasks. Across 7 experiments varying in
presentation format, timing, stimulus set, and distractor number, we observed
clear disruptive effects of executive load and visual distraction, but relatively
minimal evidence supporting an interactive relationship between these factors.
These findings are in line with recent evidence using delay-based interference,
and suggest that different forms of attentional selection operate relatively
independently in visual working memory. (PsycINFO Database Record
PMID- 28414500
TI - Location-coding account versus affordance-activation account in handle-to-hand
correspondence effects: Evidence of Simon-like effects based on the coding of
action direction.
AB - An increasing number of studies have shown a close link between perception and
action, which is supposed to be responsible for the automatic activation of
actions compatible with objects' properties, such as the orientation of their
graspable parts. It has been observed that left and right hand responses to
objects (e.g., cups) are faster and more accurate if the handle orientation
corresponds to the response location than when it does not. Two alternative
explanations have been proposed for this handle-to-hand correspondence effect:
location coding and affordance activation. The aim of the present study was to
provide disambiguating evidence on the origin of this effect by employing object
sets for which the visually salient portion was separated from, and opposite to
the graspable 1, and vice versa. Seven experiments were conducted employing both
single objects and object pairs as visual stimuli to enhance the contextual
information about objects' graspability and usability. Notwithstanding these
manipulations intended to favor affordance activation, results fully supported
the location-coding account displaying significant Simon-like effects that
involved the orientation of the visually salient portion of the object stimulus
and the location of the response. Crucially, we provided evidence of Simon-like
effects based on higher-level cognitive, iconic representations of action
directions rather than based on lower-level spatial coding of the pure position
of protruding portions of the visual stimuli. (PsycINFO Database Record
PMID- 28414501
TI - Spelling ability selectively predicts the magnitude of disruption in unspaced
text reading.
AB - We examined the effect of individual differences in written language proficiency
on unspaced text reading in a large sample of skilled adult readers who were
assessed on reading comprehension and spelling ability. Participants' eye
movements were recorded as they read sentences containing a low or high frequency
target word, presented with standard interword spacing, or in one of three
unsegmented text conditions that either preserved or eliminated word boundary
information. The average data replicated previous studies: unspaced text reading
was associated with increased fixation durations, a higher number of fixations,
more regressions, reduced saccade length, and an inflation of the word frequency
effect. The individual differences results provided insight into the mechanisms
contributing to these effects. Higher reading ability was associated with greater
overall reading speed and fluency in all conditions. In contrast, spelling
ability selectively modulated the effect of interword spacing with poorer
spelling ability predicting greater difficulty across the majority of sentence-
and word-level measures. These results suggest that high quality lexical
representations allowed better spellers to extract lexical units from unfamiliar
text forms, inoculating them against the disruptive effects of being deprived of
spacing information. (PsycINFO Database Record
PMID- 28414502
TI - Change in explicit and implicit motivation toward physical activity and sedentary
behavior in pulmonary rehabilitation and associations with postrehabilitation
behaviors.
AB - OBJECTIVE: The aim of this study was twofold: (a) to determine whether Theory of
Planned Behavior (TPB) variables and implicit attitudes toward physical activity
and sedentary behavior would change during a 5-week pulmonary rehabilitation (PR)
program, and (b) to investigate the relationships between behavioral intentions,
implicit attitudes, physical activity, and sedentary behavior in
postrehabilitation. DESIGN: Out of 142 patients with respiratory disease included
in this study, 119 completed 2 questionnaires measuring TPB variables with regard
to physical activity and sedentary behavior, and an Implicit Association Test
(IAT) measuring implicit attitudes toward physical activity in contrast to
sedentary behavior. The TPB questionnaires and the IAT were administered at the
beginning (Time 1) and the end of the program (Time 2). Six months after the
program (Time 3), 62 patients provided self-reported measures of their
recreational physical activity and screen-based, leisure-time sedentary behavior.
RESULTS: Over the course of pulmonary rehabilitation, perceived behavioral
control and intentions toward physical activity increased, as did social norms
and perceived behavioral control toward sedentary behavior; implicit attitudes
were also more positive toward physical activity. Implicit attitudes at the end
of PR (Time 2) were significantly associated with postrehabilitation physical
activity (Time 3). CONCLUSIONS: TPB variables toward physical activity and
sedentary behavior as well as implicit attitudes were enhanced during PR. At 6
months, implicit attitudes were significantly associated with physical activity.
These results suggest that motivation, particularly implicit attitudes, should be
targeted in future behavioral interventions in order to optimize the effects of
rehabilitation on physical activity maintenance. (PsycINFO Database Record
PMID- 28414503
TI - Parents' role in early adolescent self-injury: An application of self
determination theory.
AB - OBJECTIVE: We applied self-determination theory to examine a model whereby
perceived parental autonomy support directly and indirectly affects nonsuicidal
self-injury (NSSI) through difficulties in emotion regulation. METHOD: 639
participants (53% female) with a mean age of 13.38 years (SD = 0.51) completed
the How I Deal with Stress Questionnaire as a screener for NSSI, the Perceptions
of Parents Scale, and the Difficulties in emotion Regulation Scale. Participants
who indicated having ever hurt themselves on purpose without the intent to die (n
= 116, 66% female) were classified in the NSSI lifetime group. RESULTS: A
mediation analysis with bootstrapping procedure revealed that adolescents who
reported their parents as being less supportive of their need for autonomy were
more likely to have engaged in NSSI. Further, this relationship was partially
mediated by emotion regulation. CONCLUSION: Adolescents who do not perceive
autonomy support from their parents, have more difficulties regulating their
emotions, and may turn to NSSI as a means to cope. Clinical implications of the
findings suggest involving the family, and specifically, targeting parental
autonomy support may be beneficial when working with young adolescents who self
injure. (PsycINFO Database Record
PMID- 28414504
TI - The qualities of attachment with significant others and self-compassion protect
adolescents from non suicidal self-injury.
AB - Nonsuicidal self-injury (NSSI) is a serious public health problem. Identifying
the factors that could help prevent or reduce NSSI is important. The current
study examined the protective roles of the perceived qualities of current
attachment to significant others (i.e., mothers, fathers, and peers) and self
compassion in adolescent NSSI. The potential mediating effect of self-compassion
in the relationships between attachment relationships with mothers, fathers, and
peers and adolescent NSSI was also explored. Self-reported data on mother,
father, and peer attachment (each included 3 dimensions; i.e., trust,
communication, and closeness); self-compassion; and NSSI were collected from 658
secondary school students (59.9% male; Mage = 13.58 years). Participants with
NSSI experiences scored significantly higher on the perceived qualities of
current attachment with parents and self-compassion than those reporting no NSSI
experience. Attachment with peers did not distinguish the NSSI group from the Non
NSSI group. Further mediation analyses indicated that self-compassion mediated
the relationships of closeness with mothers, fathers (partially), and peers to
NSSI as well as the relationship of peer communication to NSSI. Limitations of
this study and implications regarding the protective roles of attachment and self
compassion in the prevention and intervention for NSSI are discussed. (PsycINFO
Database Record
PMID- 28414505
TI - School response to self-injury: Concerns of mental health staff and parents.
AB - Nonsuicidal self-injury (NSSI) among adolescents poses a significant problem for
schools, adolescents, and their families. However, appropriate guidelines for
addressing NSSI, including when to disclose the behavior to parents, are
currently lacking. The present study aimed to understand how school mental health
staff and parents of secondary school students view NSSI to determine how parent
school communication about NSSI, and responses to NSSI, can be improved. Nineteen
school mental health staff participated in interviews and 10 parents of
adolescents with a history of NSSI completed open-ended questionnaire items.
Staff identified that sector-wide NSSI policy and education for teachers and
principals would help them feel more supported and improve consistency in
addressing NSSI between and within schools. In contrast, parents wanted more
support directed at them rather than solely their adolescent. Implications for
policy and parental support provided by the school are discussed. (PsycINFO
Database Record
PMID- 28414506
TI - Social validity of the Social Skills Improvement System-Classwide Intervention
Program (SSIS-CIP) in the primary grades.
AB - The purpose of this study was to examine the social validity of the Social Skills
Improvement System-Classwide Intervention Program (SSIS-CIP) for teachers in the
primary grades. Participants included 45 first and second grade teachers who
completed a 16-item social validity questionnaire during each year of the SSIS
CIP efficacy trial. Findings indicated that teachers generally perceived the SSIS
CIP as a socially valid and feasible intervention for primary grades; however,
teachers' ratings regarding ease of implementation and relevance and sequence
demonstrated differences across grade levels in the second year of
implementation. (PsycINFO Database Record
PMID- 28414507
TI - The distinction between exclusivity and comorbidity within NSSI.
AB - Based on notions posited by problem behavior theory, the primary goal of the
current study was to examine the possibility that adolescents who engage in NSSI
are not a homogeneous group but are rather divided into 2 subgroups: (a)
adolescents who exclusively engage in NSSI, and (b) adolescents who are involved
in NSSI alongside other problem behaviors (e.g., drug abuse, unprotected sexual
intercourse). Participants were a school sample of 436 adolescents from 6 high
schools across Israel, who completed self-report questionnaires during school
hours on engagement in NSSI and other problem behaviors, self-esteem, self
criticism, ego clarity, coping strategies, self-efficacy to regulate affect, and
sociodemographic information. Findings indicated that 22% of the sample reported
engaging in NSSI. Adolescents who reported engaging in NSSI had higher prevalence
rates of involvement in other problem behaviors compared to those who did not
report engaging in NSSI. However, a comparison between those who exclusively
engaged in NSSI and those who were involved in NSSI alongside other problem
behaviors indicated that lower ego clarity, lower self-esteem, and poorer self
efficacy to regulate affect, alongside higher self-criticism and greater use of
disengagement coping mechanisms characterized exclusive engagement in NSSI.
Distinct theoretical models are needed to characterize different forms of NSSI:
NSSI, which is an exclusive and singular phenomenon, for which problems related
to the self are prominent, versus NSSI, which is accompanied by other problem
behaviors. Accordingly, the implications related to school psychologists' work in
the assessment, treatment, and prevention of NSSI are suggested. (PsycINFO
Database Record
PMID- 28414508
TI - Dissociating affective and semantic valence.
AB - We examined the possible dissociation between two modes of valence: affective
valence (valence of e emotional response) and semantic valence (stored knowledge
about valence of an object or event). In Experiment 1, 50 participants viewed
affective pictures that were repeatedly presented while their facial
electromyography (EMG) activation and heart rate response were continuously
recorded. Half of the participants provided self-report ratings about the valence
of their feelings and half about the valence of the stimulus. Next, all
participants performed an affective Simon task. In Experiment 2, 30 new
participants performed the affective Simon task with the repeated exposure
embedded within the task. The results showed that measures related to affective
valence (feelings-focused self-reports, heart rate, and facial EMG activations)
attenuated with repeated exposure to pleasant and unpleasant pictures, whereas
measures related to semantic valence (knowledge-focused self-reports and
congruency effect of affective Simon task) did not. These findings strongly
suggest that affective and semantic valence represent two distinct psychological
constructs. (PsycINFO Database Record
PMID- 28414509
TI - Sleep and cognitive functioning in childhood: Ethnicity, socioeconomic status,
and sex as moderators.
AB - We examined children's sleep at age 9 as a predictor of developmental
trajectories of cognitive performance from ages 9 to 11 years. The effects of
sleep on cognition are not uniform and thus we tested race/ethnicity,
socioeconomic status (SES), and sex as moderators of these associations. At the
first assessment, 282 children aged 9.44 years (52% boys, 65% European American
[EA], 35% African American [AA]) participated. Two more waves of data collection
spaced 1 year apart followed. The majority of children (63%) were living at or
below the poverty line. Children's sleep was measured objectively with actigraphy
and 2 well-established sleep parameters were derived: duration, indexed by sleep
minutes between sleep onset and wake time, and quality, indexed by efficiency.
Multiple cognitive functioning domains were examined with the Woodcock Johnson
Tests of Cognitive Abilities (WJ III). Across the sample, higher sleep
efficiency, but not duration, was associated with better cognitive performance.
Significant moderation effects emerged. Controlling for SES, AA children scored
lower on general intellectual ability and working memory (WM) at age 11 only if
they experienced lower sleep efficiency at age 9. Further, boys scored lower on
general abilities and processing speed (PS) at age 11 only if their sleep
efficiency was lower at age 9. Findings indicate that lower sleep efficiency may
contribute to lower cognitive functioning especially for AA children and boys.
These vulnerabilities appear to emerge early in development and are maintained
over time. Results underscore the importance of individual differences in
explicating relations between sleep and children's cognitive performance.
(PsycINFO Database Record
PMID- 28414510
TI - A longitudinal person-centered perspective on youth social support: Relations
with psychological wellbeing.
AB - Past research suggests that perceived social support from parents, teachers, and
peers are all positively associated with wellbeing during adolescence. However,
little longitudinal research has examined the implications of distinctive
combinations of social support for developing adolescents. To address this
limitation, we measured multiple dimensions of social support, psychological ill
health, and wellbeing in a sample of 2034 Australian adolescents (Mage = 13.7;
49.6% male) measured in Grades 8 and 11. Latent transition analyses identified a
6-profile solution for both waves of data, and revealed substantial inequality in
perceived social support. Two "socially rich" profiles corresponded to 7% of the
sample and had high social support (>1SD above sample mean) from at least two
sources. (Fully Integrated; Parent and Peer Supported). In contrast, 25% of the
sample was "socially poor," having support that was between -.65 to -.86 SD below
the sample mean for all 3 sources (Isolated profile). None of the other profiles
(Peer Supported; Moderately Supported; Weakly Supported) had levels of support
below -.37 SD from any source. Furthermore, almost all wellbeing problems were
concentrated in the Isolated Profile, with negative effects more pronounced in
Grade 11 than Grade 8. Despite feeling low parent and teacher support,
adolescents in the Peer Supported profile felt strong peer support and average to
above-average levels of wellbeing in Grades 8 and 11. However, they also had an
81% chance of making a negative transition to either the Isolated or Weakly
Supported profiles in Grade 11. (PsycINFO Database Record
PMID- 28414511
TI - Change in attachment predicts change in emotion regulation particularly among 5
HTTLPR short-allele homozygotes.
AB - In view of the theory that the attachment relationship provides a foundation for
the development of emotion regulation, here, we evaluated (a) whether change in
attachment security from 4 to 6 years predicts change in emotion regulation from
6 to 8 years and (b) whether 5-HTTLPR moderates this relation in a Norwegian
community sample (n = 678, 99.7% Caucasian). Attachment was measured with the
Manchester Child Attachment Story Task, and teachers completed the Emotion
Regulation Checklist. Attachment security was modestly stable, with children
becoming more secure over time. Regression analyses revealed that increased
attachment security from 4 to 6 forecasted increases in emotion regulation from 6
to 8 and decreased attachment security forecasted decreases in emotion
regulation. This effect was strongest among the 5-HTTLPR short-allele homozygotes
and, according to competitive model fitting, in a differential-susceptibility
manner. (PsycINFO Database Record
PMID- 28414512
TI - Adolescents' intergenerational narratives across cultures.
AB - Adolescents' intergenerational narratives-the stories they tell about their
mothers' and fathers' early experiences-are an important component of their
identities (Fivush & Merrill, 2016; Merrill & Fivush, 2016). This study explored
adolescents' intergenerational narratives across cultures. Adolescents aged 12 to
21 from 3 cultural groups in New Zealand (Chinese: n = 88; Maori: n = 91;
European: n = 91) narrated stories about their mothers' and fathers' childhood
experiences. In these narratives, New Zealand Chinese and Maori adolescents
included more identity connections (statements linking their own identities to
their parents' experiences) than did New Zealand European adolescents, and New
Zealand Chinese adolescents' intergenerational narratives were more coherent than
were New Zealand European and Maori adolescents' narratives. New Zealand Chinese
and Maori adolescents were also more likely to report didactic reasons for their
mothers' telling of the narratives, whereas New Zealand European adolescents were
more likely to report reasons of sharing family history. Across cultures, but
only in their mother narratives, adolescent girls included more references to
subjective perspectives (emotions, evaluations, and cognitions) than did
adolescent boys. Older adolescents also used more subjective perspective terms
than younger adolescents. These findings suggest that intergenerational
narratives serve different functions when adolescents across cultures explore
their identities. These narratives may be especially important for adolescents
growing up in cultures with an interdependent orientation. (PsycINFO Database
Record
PMID- 28414513
TI - Civic purpose in late adolescence: Factors that prevent decline in civic
engagement after high school.
AB - This study investigated the effects of internal and demographic variables on
civic development in late adolescence using the construct civic purpose. We
conducted surveys on civic engagement with 480 high school seniors, and surveyed
them again 2 years later. Using multivariate regression and linear mixed models,
we tested the main effects of civic purpose dimensions (beyond-the-self
motivation, future civic intention), ethnicity, and education on civic
development from Time 1 to Time 2. Results showed that while there is an overall
decrease in civic engagement in the transition out of high school, both internal
and social factors protected participants from steep civic decline. Interaction
effects varied. Ethnicity and education interacted in different ways with the
dimensions of civic purpose to predict change in traditional and expressive
political engagement, and community service engagement. (PsycINFO Database Record
PMID- 28414514
TI - Pickering emulsions in foods - opportunities and limitations.
AB - In order to critically discuss the potential of Pickering-type emulsions in food
applications this review provides the theoretical background of the stabilizing
mechanisms, the resulting requirements for particles to stabilize these systems
and the limitations resulting from these fundamental considerations. Food grade
particle systems investigated in the past are presented. It becomes obvious that
with a proper choice of a particle type, oil-in-water as well as water-in-oil
emulsions can be achieved. For highly viscous products, products with a high
internal phase volume and foams Pickering particles offer alternatives to
commonly used surfactants. Pickering emulsions might be able to offer new
approaches for fat reduction as well as encapsulation and sustained release of
active ingredients. Nevertheless, a major part of successful systems have been
achieved with silica or modified silica particles, which is not in line with the
consumer demand for clean label, natural systems or not even food grade. However,
the intriguing possibilities motivate and justify future research on the
identification of new suitable ingredients, improvement of existing formulations
and identification of new fields of application.
PMID- 28414516
TI - Effects of Having Preterm Infants Smell Amniotic Fluid, Mother's Milk, and
Mother's Odor During Heel Stick Procedure on Pain, Physiological Parameters, and
Crying Duration.
AB - OBJECTIVE: The study aims to assess effects of having preterm infants smell
amniotic fluid, mother's milk, and mother's odor during heel stick procedure on
pain, physiological parameters, and crying duration. MATERIALS AND METHODS: The
study was a randomized controlled experimental research. The population of the
study was made up of preterm infants receiving treatment and care at a neonatal
intensive care unit, where the study was conducted between January 2015 and March
2016. The study was performed with 85 preterm infants who met the selection
criteria. Infants were randomized into four groups: amniotic fluid, mother's
milk, mother's odor, and control group. Data obtained were analyzed by percentage
distributions, means, standard deviation, chi-square test, Kruskal-Wallis, and
Dunnett's test. RESULTS: While no significant difference was found between the
groups in terms of total preterm infant pain profile score before, during, and
after the heel stick procedure (p > 0.05), a significant difference was found in
terms of SO2 values (p < 0.05) and the difference was caused by the amniotic
fluid group. Although no significant difference was found between the groups in
terms of crying duration (p > 0.05), the amniotic fluid group had the lowest
score, followed by the mother's milk group, the mother's odor group, and the
control group. CONCLUSIONS: Amniotic fluid, mother's milk, and mother's odor were
not effective in preterm infants during painful procedures.
PMID- 28414515
TI - Zseq: An Approach for Preprocessing Next-Generation Sequencing Data.
AB - Next-generation sequencing technology generates a huge number of reads (short
sequences), which contain a vast amount of genomic data. The sequencing process,
however, comes with artifacts. Preprocessing of sequences is mandatory for
further downstream analysis. We present Zseq, a linear method that identifies the
most informative genomic sequences and reduces the number of biased sequences,
sequence duplications, and ambiguous nucleotides. Zseq finds the complexity of
the sequences by counting the number of unique k-mers in each sequence as its
corresponding score and also takes into the account other factors such as
ambiguous nucleotides or high GC-content percentage in k-mers. Based on a z-score
threshold, Zseq sweeps through the sequences again and filters those with a z
score less than the user-defined threshold. Zseq algorithm is able to provide a
better mapping rate; it reduces the number of ambiguous bases significantly in
comparison with other methods. Evaluation of the filtered reads has been
conducted by aligning the reads and assembling the transcripts using the
reference genome as well as de novo assembly. The assembled transcripts show a
better discriminative ability to separate cancer and normal samples in comparison
with another state-of-the-art method. Moreover, de novo assembled transcripts
from the reads filtered by Zseq have longer genomic sequences than other tested
methods. Estimating the threshold of the cutoff point is introduced using
labeling rules with optimistic results.
PMID- 28414517
TI - Internet Addiction, Psychological Distress, and Coping Responses Among
Adolescents and Adults.
AB - As Internet use grows, so do the benefits and also the risks. Thus, it is
important to identify when individuals' Internet use is problematic. In the
present study, 449 participants aged from 16 to 71 years of age were sourced from
a wide range of English-speaking Internet forums, including social media and self
help groups. Of these, 68.9% were classified as nonproblematic users, 24.4% as
problematic users, and 6.7% as addictive Internet users. High use of discussion
forums, high rumination levels, and low levels of self-care were the main
contributing factors to Internet addiction (IA) among adolescents. For adults IA
was mainly predicted through engagement in online video gaming and sexual
activity, low email use, as well as high anxiety and high avoidant coping.
Problematic Internet users scored higher on emotion and avoidance coping
responses in adults and higher on rumination and lower on self-care in
adolescents. Avoidance coping responses mediated the relationship between
psychological distress and IA. These findings may assist clinicians with
designing interventions to target different factors associated with IA.
PMID- 28414518
TI - Advanced synchrotron-based and globar-sourced molecular (micro) spectroscopy
contributions to advances in food and feed research on molecular structure,
mycotoxin determination, and molecular nutrition.
AB - Mycotoxin contamination has been a worldwide problem for food and feeds
production for a long time. There is an obviously increased focus of the food and
feed industry toward the reduction of mycotoxin concentration in both the raw
materials and finished products. Therefore, both effective qualitative and
quantitative techniques for the determination of mycotoxins are required to
minimize their harmful effects. Conventional wet chemical methods usually are
time-consuming, expensive, and rely on complex extraction and cleanup
pretreatments. Synchrotron-based and globar-based molecular spectroscopy have
shown great potential to be developed as rapid and nondestructive tools for the
determination of molecular structure, molecular nutrition and mycotoxins in feed
and food. This article reviews the common types of mycotoxins in feed and food,
their toxicity, as well as the conventional detection methods. The principle of
advanced molecular spectroscopy techniques and their application prospects for
mycotoxin detection are discussed. Recent progress in food and feed research with
molecular spectroscopy techniques is highlighted. This review provides a
potential and insight into how to determine the structure and mycotoxins of feed
and food on a molecular basis with advanced Synchrotron-based and globar-based
molecular (micro) spectroscopy.
PMID- 28414519
TI - Effect of a Food Supplement Containing L-Methionine on Urinary Tract Infections
in Pregnancy: A Prospective, Multicenter Observational Study.
AB - OBJECTIVE: Adjuvants or alternatives to antibiotics in urinary tract infections
(UTIs) during pregnancy seem advisable because of possible fetal stress. The
present study assessed the effectiveness of a food supplement containing L
methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a
treatment for symptomatic UTIs in pregnancy. DESIGN: Pregnant patients with
symptomatic cystitis were screened for UTIs in three different clinical centers.
Those unwilling to take antibiotics were offered two alternative treatments: (A)
a 1-week treatment with the food supplement or (B) a week in which they were
advised to increase their fluid consumption to more than 1.5 L daily. After 1
week, group B patients who still had positive urine cultures (UCs) or had no UC
performed took the food supplement for an additional week. UCs were performed on
all patients at the first visit (w0) and on most of them at 7 days (w1). Patients
who were still positive at w1 or had no UC performed at w1 had UC performed 14
days (w2) thereafter. RESULTS: Of 264 pregnant women enrolled, 216 joined group
A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those
in group B had negative UCs (p = 0.003). The reduction of bacterial load was
42.2% +/- 8.0% and 4.5% +/- 9.2%, respectively (p < 0.0001). At w1, symptoms
disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B
(p = 0.03). At w2, 30 of 32 group B patients who switched to taking the
supplement for the second week had negative UCs, including 20 who had been
positive at w1. At w2, all group A patients had negative UCs. No side effects
were reported. CONCLUSIONS: The food supplement provided effective treatment and
might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in
pregnancy.
PMID- 28414520
TI - Rare Genetic Variants in PARN Are Associated with Pulmonary Fibrosis in Families.
PMID- 28414521
TI - Representations of Search Spaces in the Problem of Mutational Pressure
Optimization According to Protein-Coding Sequences.
AB - The proper representation of the search space is the fundamental step in every
optimization task, because it has a decisive impact on the quality of potential
solutions. In particular, this problem appears when the search spaces are
nonstandard and complex, with the large number of candidate solutions that differ
from classical forms usually investigated. One of such spaces is the set of
continuous-time, homogenous, and stationary Markov processes. They are commonly
used to describe biological phenomena, for example, mutations in DNA sequences
and their evolution. Because of the complexity of these processes, the
representation of their search space is not an easy task but it is important for
effective solving of the biological problems. One of them is optimality of
mutational pressure acting on protein-coding sequences. Therefore, we described
three representations of the search spaces and proposed several specific
evolutionary operators that are used in evolutionary-based optimization
algorithms to solve the biological problem of mutational pressure optimality. In
addition, we gave a general formula for the fitness function, which can be used
to measure the quality of potential solutions. The structures of these solutions
are based on two models of DNA evolution described by substitution-rate matrices,
which are commonly used in phylogenetic analyzes. The proposed representations
have been successfully utilized in various issues, and the obtained results are
very interesting from a biological point of view. For example, they show that
mutational pressures are, to some extent, optimized to minimize cost of amino
acid substitutions in proteins.
PMID- 28414522
TI - A Comparison of Breast Milk and Sucrose in Reducing Neonatal Pain During Eye Exam
for Retinopathy of Prematurity.
AB - BACKGROUND: This double-blind randomized controlled experimental study aimed to
determine the effects of breast milk and sucrose in reducing pain in preterm
infants during retinopathy of prematurity (ROP) examination. MATERIALS AND
METHODS: This study was conducted with 60 preterm infants (breast milk group =
20, sucrose group = 20, and control/distilled water group = 20) meeting the
inclusion criteria. The data were collected with the use of an Infant Evaluation
Form, Procedure Monitoring Form, and Premature Infant Pain Profile (PIPP). The
preterm infants were provided with 1 mL of breast milk, sucrose, and distilled
water before the ROP examination. The pain level in preterm infants was measured
by the PIPP 5 minutes before, during, and 5 minutes after the ROP examination.
The ROP examinations were video recorded, and videos were evaluated by three
observers blinded to the study. RESULTS: No significant difference was determined
between the three groups in terms of their postconceptional and postnatal ages,
their body weights at birth and during the ROP examination. The PIPP scores of
the preterm infants in the three groups were higher during the ROP examination
and were not significantly different. The PIPP scores of the control group were
significantly higher than those in the breast milk and sucrose groups after the
ROP examination (p < 0.001). The preterm infants in the breast milk group
recovered and returned to their initial values more quickly after the ROP
examination than the infants in the sucrose group. CONCLUSION: To reduce pain in
preterm infants during ROP examination, breast milk is recommended.
PMID- 28414523
TI - Presence of Toxoplasma gondii in Drinking Water from an Endemic Region in
Southern Mexico.
AB - Toxoplasmosis can be acquired through the ingestion of contaminated drinking
water with oocysts of Toxoplasma gondii, highly resistant to the routinely
disinfection processes; based on chlorination commonly used in the water supply
industry. The aim of this study was to determine the presence of T. gondii DNA in
samples of public drinking water from an endemic region of southern Mexico. In
total 74 samples of water (5 L each) were collected from the three well fields
(I, II, and III) and 71 independent wells, distributing public drinking water to
the city of Merida Yucatan, after passing through the chlorination process. Water
samples were filtered and concentrated by a sucrose solution, then DNA was
extracted and evaluated through a nested-PCR (nPCR) specific for T. gondii.
Positive samples were detected in 5.4% (4/74) of the water samples. This is the
first report of the presence of T. gondii DNA in public drinking water from a
large city in southern Mexico, where their consumption without any
postpurification treatment could pose a risk for acquiring the infection in the
urban population.
PMID- 28414525
TI - Influence of physical and biological variability and solution methods in fruit
and vegetable quality nondestructive inspection by using imaging and near
infrared spectroscopy techniques: A review.
AB - Over the past decades, imaging and spectroscopy techniques have been rapidly
developing and widely applied in nondestructive fruit and vegetable quality
assessment. The physical properties (including size, shape, color, position, and
temperature) and biological properties (including cultivar, season, maturity
level and geographical origin) of fruits and vegetables vary from one to another.
A great variety of physical and biological properties of agricultural products
influence the optical propagation properties and interaction behaviors with
incident light, thus decreasing the quality inspection accuracy. Many attempts
have been made in image correction and spectral compensation methods to improve
the inspection accuracy. This paper gives a detailed summary about influence of
physical and biological variability, as well as the correction and compensation
methods for eliminating or reducing the effects in fruit and vegetable quality
nondestructive inspection by using imaging and spectroscopy techniques. The
advantages and disadvantages of the solution methods are discussed and
summarized. Additionally, the future challenges and potential trends are also
reported.
PMID- 28414526
TI - Assessing the Impact of Assemblers on Virus Detection in a De Novo Metagenomic
Analysis Pipeline.
AB - Applying high-throughput sequencing to pathogen discovery is a relatively new
field, the objective of which is to find disease-causing agents when little or no
background information on disease is available. Key steps in the process are the
generation of millions of sequence reads from an infected tissue sample, followed
by assembly of these reads into longer, contiguous stretches of nucleotide
sequences, and then identification of the contigs by matching them to known
databases, such as those stored at GenBank or Ensembl. This technique, that is,
de novo metagenomics, is particularly useful when the pathogen is viral and
strong discriminatory power can be achieved. However, recently, we found that
striking differences in results can be achieved when different assemblers were
used. In this study, we test formally the impact of five popular assemblers
(MIRA, VELVET, METAVELVET, SPADES, and OMEGA) on the detection of a novel virus
and assembly of its whole genome in a data set for which we have confirmed the
presence of the virus by empirical laboratory techniques, and compare the overall
performance between assemblers. Our results show that if results from only one
assembler are considered, biologically important reads can easily be overlooked.
The impacts of these results on the field of pathogen discovery are considered.
PMID- 28414524
TI - A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease. An
International Working Group Perspective.
PMID- 28414528
TI - A Note from the Publisher.
PMID- 28414529
TI - Introduction Arthur D. Smith, MD: Humility, Hard Work, and Grace.
PMID- 28414527
TI - Advantages and limitations of in vitro and in vivo methods of iron and zinc
bioavailability evaluation in the assessment of biofortification program
effectiveness.
AB - Biofortification aims to improve the micronutrient concentration of staple food
crops through the best practices of breeding and modern biotechnology. However,
increased zinc and iron concentrations in food crops may not always translate
into proportional increases in absorbed zinc (Zn) and iron (Fe). Therefore,
assessing iron and zinc bioavailability in biofortified crops is imperative to
evaluate the efficacy of breeding programs. This review aimed to investigate the
advantages and limitations of in vitro and in vivo methods of iron and zinc
bioavailability evaluation in the assessment of biofortification program
effectiveness. In vitro, animal and isotopic human studies have shown high iron
and zinc bioavailability in biofortified staple food crops. Human studies provide
direct knowledge regarding the effectiveness of biofortification, however, human
studies are time consuming and are more expensive than in vitro and animal
studies. Moreover, in vitro studies may be a useful preliminary screening method
to identify promising plant cultivars, however, these studies cannot provide data
that are directly applicable to humans. None of these methods provides complete
information regarding mineral bioavailability, thus, a combination of these
methods should be the most appropriate strategy to investigate the effectiveness
of zinc and iron biofortification programs.
PMID- 28414530
TI - Hope Amidst Horror: Documenting the Effects of the "War On Drugs" Among Female
Sex Workers and Their Intimate Partners in Tijuana, Mexico.
AB - Sensationalistic media coverage has fueled stereotypes of the Mexican border city
of Tijuana as a violent battleground of the global drug war. While the drug war
shapes health and social harms in profoundly public ways, less visible are the
experiences and practices of hope that forge communities of care and represent
more private responses to this crisis. In this article, we draw on ethnographic
fieldwork and photo elicitation with female sex workers who inject drugs and
their intimate, non-commercial partners in Tijuana to examine the personal
effects of the drug war. Drawing on a critical phenomenology framework, which
links political economy with phenomenological concern for subjective experience,
we explore the ways in which couples try to find hope amidst the horrors of the
drug war. Critical visual scholarship may provide a powerful alternative to
dominant media depictions of violence, and ultimately clarify why this drug war
must end.
PMID- 28414531
TI - A System Architecture for Efficient Transmission of Massive DNA Sequencing Data.
AB - The DNA sequencing data analysis pipelines require significant computational
resources. In that sense, cloud computing infrastructures appear as a natural
choice for this processing. However, the first practical difficulty in reaching
the cloud computing services is the transmission of the massive DNA sequencing
data from where they are produced to where they will be processed. The daily
practice here begins with compressing the data in FASTQ file format, and then
sending these data via fast data transmission protocols. In this study, we
address the weaknesses in that daily practice and present a new system
architecture that incorporates the computational resources available on the
client side while dynamically adapting itself to the available bandwidth. Our
proposal considers the real-life scenarios, where the bandwidth of the connection
between the parties may fluctuate, and also the computing power on the client
side may be of any size ranging from moderate personal computers to powerful
workstations. The proposed architecture aims at utilizing both the communication
bandwidth and the computing resources for satisfying the ultimate goal of
reaching the results as early as possible. We present a prototype implementation
of the proposed architecture, and analyze several real-life cases, which provide
useful insights for the sequencing centers, especially on deciding when to use a
cloud service and in what conditions.
PMID- 28414532
TI - From the Editor-in-Chief's Desk.
PMID- 28414533
TI - Lithium and Heart Block in an Adolescent Boy.
PMID- 28414534
TI - Deprescribing to improve care.
PMID- 28414535
TI - Controlling the controllable in community palliative care.
PMID- 28414536
TI - Spring has officially sprung.
PMID- 28414537
TI - Developing a caseload classification tool for community nursing.
AB - Acuity and dependency in the community nursing caseload in combination with safe
staffing levels are a national issue of concern. Current evidence suggests that
there are no clear approaches to determining staff capacity and skill mix in
these community settings. As community nursing caseloads are large with differing
complexities, there is a need to allocate community nursing with the best skill
mix to achieve the best patient outcomes. A city-wide service improvement
initiative developed a tool to classify and categorise patient demand and this
was linked to an electronic patient record system. The aim was to formulate an
effective management response to different levels of acuity and dependency within
community nursing teams and a consensus approach was used to allow the definition
of complexity for twelve packages of care. The tool was piloted by a group of
community nurses to assess the validity as a method to achieve a caseload
classification. Seventy nurses were trained and applied the tool to 3000 patient
referrals. Based on this, standards of care were agreed including expectations of
assessment, intervention, visit length and frequency. Community nursing caseloads
can now be organised according to acuity and complexity of patient need, which
determines allocation of staff and skill mix.
PMID- 28414538
TI - Part 3: Impact of systemic conditions and medications on oral health.
AB - The people who are treated in the community setting will often have multiple
comorbidities. Systemic medical conditions can have a negative impact on oral
health. In addition, the medications used to treat systemic conditions may also
themselves cause oral symptoms. As a large proportion of patients treated by the
community nursing team will be elderly, this paper will focus on common geriatric
conditions that can display oral or dental symptoms. The effects of medications
will be discussed and linked to oral complaints patients may express. The primary
aims are to give a broad overview of the oral effects of ageing, of illness and
of polypharmacy and advise on how these can be best managed by the nursing team.
PMID- 28414539
TI - Sleep and dementia.
PMID- 28414540
TI - The future of community nursing: Hospital in the Home.
AB - With an increasing ageing population who often have multiple long-term
conditions, there is a growing need to provide an alternative type of care to the
traditional hospital-based model. 'Hospital in the Home' is a model that provides
integrated care for patients in their home. The @home service was established in
2013 by Guy's and St Thomas' NHS Foundation Trust. The service provides health
care in patients' home, supporting early discharge from hospital as well as
preventing avoidable admissions and readmissions saving valuable hospital bed
days and reducing length of stay. This article describes the service available
with the use of a case study of a 78-year-old lady who was referred by the London
Ambulance Service with exacerbation of chronic obstructive pulmonary disease
(COPD). This case study highlights the ability to assess, treat and manage an
acutely unwell patient with newly diagnosed heart failure in the community
without the need for hospitalisation. This type of integrated care model with a
multidisciplinary team is a feasible alternative to the traditional models of
care in both the acute and community settings.
PMID- 28414541
TI - Stoma care: an update on current guidelines for community nurses.
PMID- 28414542
TI - Revisiting constipation management in the community.
PMID- 28414543
TI - Private deprivation of liberty.
AB - The Court of Appeal has ruled that a person is deprived of their liberty in their
own home even though care and treatment was provided in the person's own home and
funded using the person's money. In this article Richard Griffith discusses when
a private deprivation of liberty must be authorised by a welfare order from the
Court of Protection.
PMID- 28414544
TI - Part 2: Assessing foot risk status and points of action.
PMID- 28414545
TI - Modular use of human body models of varying levels of complexity: Validation of
head kinematics.
AB - OBJECTIVE: The significant computational resources required to execute detailed
human body finite-element models has motivated the development of faster running,
simplified models (e.g., GHBMC M50-OS). Previous studies have demonstrated the
ability to modularly incorporate the validated GHBMC M50-O brain model into the
simplified model (GHBMC M50-OS+B), which allows for localized analysis of the
brain in a fraction of the computation time required for the detailed model. The
objective of this study is to validate the head and neck kinematics of the GHBMC
M50-O and M50-OS (detailed and simplified versions of the same model) against
human volunteer test data in frontal and lateral loading. Furthermore, the effect
of modular insertion of the detailed brain model into the M50-OS is quantified.
METHODS: Data from the Navy Biodynamics Laboratory (NBDL) human volunteer
studies, including a 15g frontal, 8g frontal, and 7g lateral impact, were
reconstructed and simulated using LS-DYNA. A five-point restraint system was used
for all simulations, and initial positions of the models were matched with
volunteer data using settling and positioning techniques. Both the frontal and
lateral simulations were run with the M50-O, M50-OS, and M50-OS+B with active
musculature for a total of nine runs. RESULTS: Normalized run times for the
various models used in this study were 8.4 min/ms for the M50-O, 0.26 min/ms for
the M50-OS, and 0.97 min/ms for the M50-OS+B, a 32- and 9-fold reduction in run
time, respectively. Corridors were reanalyzed for head and T1 kinematics from the
NBDL studies. Qualitative evaluation of head rotational accelerations and linear
resultant acceleration, as well as linear resultant T1 acceleration, showed
reasonable results between all models and the experimental data. Objective
evaluation of the results for head center of gravity (CG) accelerations was
completed via ISO TS 18571, and indicated scores of 0.673 (M50-O), 0.638 (M50
OS), and 0.656 (M50-OS+B) for the 15g frontal impact. Scores at lower g levels
yielded similar results, 0.667 (M50-O), 0.675 (M50-OS), and 0.710 (M50-OS+B) for
the 8g frontal impact. The 7g lateral simulations also compared fairly with an
average ISO score of 0.565 for the M50-O, 0.634 for the M50-OS, and 0.606 for the
M50-OS+B. The three HBMs experienced similar head and neck motion in the frontal
simulations, but the M50-O predicted significantly greater head rotation in the
lateral simulation. CONCLUSION: The greatest departure from the detailed occupant
models were noted in lateral flexion, potentially indicating the need for further
study. Precise modeling of the belt system however was limited by available data.
A sensitivity study of these parameters in the frontal condition showed that belt
slack and muscle activation have a modest effect on the ISO score. The reduction
in computation time of the M50-OS+B reduces the burden of high computational
requirements when handling detailed HBMs. Future work will focus on harmonizing
the lateral head response of the models and studying localized injury criteria
within the brain from the M50-O and M50-OS+B.
PMID- 28414546
TI - Behavioral Parent Training in Infancy: What About the Parent-Infant Relationship?
AB - Behavioral parent training (BPT) and attachment interventions have demonstrated
efficacy in improving outcomes for young children. Despite theoretical overlap in
these approaches, the literature has evolved separately, particularly with
respect to outcome measurement in BPT. We examined the impact of the Infant
Behavior Program (IBP), a brief home-based adaptation of Parent-Child Interaction
Therapy, on changes in attachment-based caregiving behaviors (sensitivity,
warmth, and intrusiveness) at postintervention and 3- and 6-month follow-ups
during a videotaped infant-led play. Sixty mother-infant dyads were randomly
assigned to receive the IBP (n = 28) or standard care (n = 30). Infants were an
average age of 13.52 months and predominately from ethnic or racial minority
backgrounds (98%). We used bivariate correlations to examine the association
between attachment-based caregiving behaviors and behaviorally based parenting do
and don't skills and structural equation modeling to examine the direct effect of
the IBP on attachment-based caregiving behaviors and the indirect effect of
behaviorally based parenting skills on the relation between intervention group
and attachment-based caregiving behaviors. Behaviorally based parenting do and
don't skills were moderately correlated with attachment-based caregiving
behaviors. Results demonstrated a direct effect of the IBP on warmth and
sensitivity at postintervention and 3- and 6-month follow-ups. The direct effect
of the IBP on warmth and sensitivity at the 3- and 6-month follow-ups was
mediated by increases in parenting do skills at postintervention. Findings
suggest that behaviorally based parenting skills targeted in BPT programs have a
broader impact on important attachment-based caregiving behaviors during the
critical developmental transition from infancy to toddlerhood.
PMID- 28414547
TI - Distribution of PERIOD-immunoreactive neurons and temporal change of the
immunoreactivity under long-day and short-day conditions in the larval brain of
the flesh fly Sarcophaga similis.
AB - The flesh fly Sarcophaga similis show a clear photoperiodic response; they
develop into adults under long days, whereas they arrest their development at the
pupal stage under short days. Although the involvement of a circadian clock in
photoperiodic time measurement is suggested in this species, the anatomical
location of the clock neurons responsible for the time measurement has been
unknown. We detected two PERIOD-immunoreactive cell clusters in the larval brain;
one cluster was located at the dorsoanterior region and the other at the medial
region. We further investigated their temporal changes in PERIOD-immunoreactivity
and compared their patterns under different photoperiods.
PMID- 28414548
TI - Assessing State Mental Contamination: Development and Preliminary Validation of
the State Mental Contamination Scale.
AB - This 2-part study described the development and preliminary validation of the
State Mental Contamination Scale (SMCS), a multi-item self-report measure of
state mental contamination. In Study 1, community adults (N = 211) in the United
States were randomly assigned to a pathogen disgust, moral disgust, or neutral
condition and then completed the SMCS. Study 1 results supported a 1-factor
structure of the SMCS items. Scores on the SMCS items evidenced good internal
consistency and strong interitem correlations. SMCS scores were significantly
greater following the 2 disgust conditions relative to the neutral condition and
a full range of SMCS scores were found in the disgust conditions. An independent
sample of community adults (N = 121) from the United States participated in Study
2 to extend Study 1 results. Study 2 results indicated that SMCS scores were
manipulated independently of trait mental contamination, more strongly related to
convergent than a discriminant measure, and shared unique variance with a
criterion measure after controlling for convergent measures. The future use of
the SMCS is discussed.
PMID- 28414549
TI - Do marine algal polyphenols have antidiabetic, antihyperlipidemic or anti
inflammatory effects in humans? A systematic review.
AB - Cardiovascular disease and type 2 diabetes are leading causes of morbidity and
mortality globally. Marine algal polyphenols have potential to reduce the risk of
these conditions, however, little is known about their impact in humans. This
systematic review investigates the antidiabetic, antihyperlipidemic and anti
inflammatory effects of marine polyphenols in humans. Scopus, Medline, PsychInfo,
Embase and Cochrane Library databases were searched in November 2016. Eligible
studies included (1) human adults, (2) marine polyphenol intervention, (3) blood
lipid, glucose, insulin or inflammatory marker outcomes, and (4) were a
randomized-controlled trial. One postprandial cross-over trial and four parallel
design trials were included involving 271 adults. Analysis across studies was
performed using Cohen's d effect sizes. Supplementation with polyphenol-rich
extracts had small-to-medium positive effects on fasting blood glucose, total
cholesterol and LDL-cholesterol; however, there is inadequate evidence as yet to
confirm if these are consistent effects. Further randomized-controlled trials
should investigate polyphenols from Ecklonia cava and other macroalgal sources,
to determine if there is a role for marine polyphenols in reducing the risk
factors of chronic disease in humans. (PROSPERO registration number
CRD42015016890).
PMID- 28414551
TI - Long Noncoding RNA MNX1-AS1 Knockdown Inhibits Cell Proliferation and Migration
in Ovarian Cancer.
AB - Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators that
govern fundamental biological processes and disease pathogenesis. LncRNA MNX1-AS1
has been reported to promote cell proliferation and invasion in gallbladder
cancer, but its biological role and regulatory mechanism in ovarian cancer are
poorly defined. In this study, it was found that higher expression of lncRNA MNX1
AS1 is closely associated with International Federation of Gynecology and
Obstetrics stage and lymphatic metastasis in ovarian cancer patients. RNA
interference (RNAi) to downregulate the expression of lncRNA MNX1-AS1 was used in
the ovarian cancer cell lines, OVCA433 and SKOV-3. CCK-8, EdU staining, and
colony formation assays was used to test the viability and proliferation ability
of these cells. Wound healing and transwell migration assays were performed to
determine the migration ability of the cells. Cell cycle progression and
apoptotic assays were carried out using flow cytometry. These in vitro loss-of
function experiments revealed that downregulation of lncRNA MNX1-AS1 suppressed
cell proliferation, colony formation, cell migration ability, induced cell cycle
arrest at the G0/G1 phase, and promoted apoptosis. Furthermore, MNX1-AS1
knockdown altered the protein expressions of CDK4, cyclin D, Bax, and Bcl-2.
These findings demonstrated for the first time that lncRNA MNX1-AS1 functions as
an oncogene in ovarian cancer and could be a potential target for this disease.
PMID- 28414550
TI - Expression of Long Noncoding RNA Urothelial Cancer Associated 1 Promotes
Cisplatin Resistance in Cervical Cancer.
AB - Cisplatin resistance is still one of the main reasons for failure of clinical
therapy for cervical cancer. But the underlying molecular mechanisms involved in
cisplatin resistance of cervical cancer have still remained unclear. Recent
studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding
transcripts, which might play a key role in cancer biogenesis and prognosis. One
of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote
different types of cancer cell proliferation, migration, and invasion. This study
showed that overexpression of UCA1 confers cisplatin resistance by promoting
cancer cell proliferation and inhibiting apoptosis. In addition, knockdown of
UCA1 remarkably decreased cisplatin resistance in cervical cancer cells.
Moreover, results also indicated that UCA1 was involved in signaling pathways
modulating cell apoptosis and proliferation. UCA1 suppressed apoptosis by
downregulating caspase 3 and upregulating CDK2, whereas enhanced cell
proliferation by increased level of survivin and decreased level of p21. This
study reports for the first time that UCA1 might play an important role in the
cisplatin resistance in cervical cancer, and also explain partially how UCA1
promotes cisplatin resistance in cancer cells. These results provide evidence to
support that UCA1 can be used as a potential target for a novel therapeutic
strategy for cervical cancer.
PMID- 28414552
TI - AAV Is Now a Medicine: We Had Better Get This Right.
PMID- 28414553
TI - GD-RDA: A New Regularized Discriminant Analysis for High-Dimensional Data.
AB - High-throughput techniques bring novel tools and also statistical challenges to
genomic research. Identification of which type of diseases a new patient belongs
to has been recognized as an important problem. For high-dimensional small sample
size data, the classical discriminant methods suffer from the singularity problem
and are, therefore, no longer applicable in practice. In this article, we propose
a geometric diagonalization method for the regularized discriminant analysis. We
then consider a bias correction to further improve the proposed method.
Simulation studies show that the proposed method performs better than, or at
least as well as, the existing methods in a wide range of settings. A microarray
dataset and an RNA-seq dataset are also analyzed and they demonstrate the
superiority of the proposed method over the existing competitors, especially when
the number of samples is small or the number of genes is large. Finally, we have
developed an R package called "GDRDA" which is available upon request.
PMID- 28414554
TI - Antitumor activity of the pachymic acid in nasopharyngeal carcinoma cells.
AB - OBJECTIVE: To investigate the antitumour efficacy of pachymic acid (PA), which is
a fungal extract component, on nasopharyngeal carcinoma (NPC) cells CNE-1, CNE-2.
METHODS: We have chosen NPC cell line CNE-2 for the study, and the cells were
treated with PA before the detection. CCK-8 assay was used to detect the
proliferative ability, and Annexin V-PI double staining was used for the
detection of apoptosis rate; and the nucleus damage was detected by transmission
electron microscope, the protein expression of the DNA damage pathway were
detected by Western blot. RESULTS: PA can significantly inhibited proliferation
of CNE-1, CNE-2 cells. The proportion of apoptotic cells of all cell lines
gradually increased in a dose-dependent manner induced by PA, P < 0.05.
Meanwhile, the nucleus could be caused morphological changes and the expression
of DNA damage-related proteins was upregulated by PA in CNE-2. CONCLUSIONS: PA
can significantly inhibit cell proliferation and increase the apoptosis rates and
may induce the apoptosis of the human NPC cells.
PMID- 28414555
TI - Making the Right Thing Easier to Do: Standardized Integration of Oncology and
Palliative Care.
PMID- 28414556
TI - Dynamic Equilibrium.
PMID- 28414557
TI - Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica
nanoparticles as a targeted drug delivery system for bladder cancer therapy.
AB - We reported a simple polydopamine (PDA)-based surface modification method to
prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and
peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the
therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in
terms of size, size distribution, zeta potential, transmission electron
microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading
content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA
PEP had similar release kinetic profiles of DOX. The PDA coating well controlled
DOX release and was highly sensitive to pH value. Confocal laser scanning
microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human
bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest
cellular uptake efficiency due to ligand-receptor recognition. The antitumor
effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and
by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX
loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded
MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT
1376 cells, can be used as a potential targeted drug delivery system for bladder
cancer therapy.
PMID- 28414558
TI - Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1
Responses in Behcet's Disease.
AB - OBJECTIVES: Interleukin-17 (IL-17) has been associated with the pathogenesis of
various autoimmune/inflammatory diseases. The aim of this study was to
investigate the expression of Th17-related immunity in an innate immunity
dominated vasculitis, namely Behcet's disease (BD). METHODS: Peripheral blood
mononuclear cells from 37 patients (age: 38.5 +/- 9.8 years) with BD, and 25
healthy controls (HC) (age: 39.1 +/- 9.3 years), were cultured in Th17-inducing
conditions (IL-6, Phytohemagglutinin (PHA), IL-1beta, and IL-23) for 6 days.
Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon
gamma (IFN-gamma), and IL-17 antibodies to determine the intracellular cytokine
secretion by flow cytometry. RESULTS: IL-17 expression by CD8+ and gammadelta+ T
cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No
differences were observed between the groups in the IL-17 production by B cells.
Under Th17-inducing conditions, production of IFN-gamma by CD4+, CD8+, and
gammadelta+ T cells was also higher in BD compared to HC (p < 0.05 in all).
CONCLUSION: Our results suggest that under Th17-stimulating conditions, T cells
express both IL-17 and IFN-gamma in BD. More prominent IL-17 and IFN-gamma
production by all lymphocyte subsets in BD might be associated with the increased
innate responses, early tissue neutrophil infiltrations and late adaptive
immunity in BD.
PMID- 28414559
TI - Evaluating the Cost and Utility of Mandating Schools to Stock Epinephrine Auto
injectors.
AB - BACKGROUND: The Michigan Legislature mandated that all public schools stock
epinephrine auto-injectors (EAIs). A minimal amount is known regarding the
incremental value of EAIs in schools. Our primary objective was to describe the
frequency of administration of epinephrine for EMS patients with acute allergic
reactions in public schools. Our secondary objective was to estimate the cost of
mandating public schools to stock EAIs. METHODS: We performed a retrospective
cohort study of EMS cases with an impression of allergic reaction and who
received epinephrine recorded in the 2014 Michigan EMS Information System (MI
EMSIS). We abstracted patient demographics, incident location by address to
identify public schools, source of epinephrine given, and suspected allergen if
known. We calculated advanced life support (ALS) response times to assess
temporal impact of school EAIs in communities with ALS systems. We estimated the
unsubsidized annual procurement cost of this mandate for Michigan public schools
(N = 4,039), using range of costs for the required 2 EAIs (adult and pediatric)
as estimated by the legislature ($140/each) and recently reported costs for
commercial sources ($1,200). Training costs were not included. Descriptive
statistics are reported. RESULTS: During this period, there were 1,550,009 EMS
cases in the state with 631 receiving non-cardiac arrest epinephrine for presumed
anaphylaxis, of which 23 cases were in public schools. Reported allergens were
most often food 12 (51.2%), insect stings 4(22.2%) or unknown 7(30.4%). Among
these patients, the source for epinephrine used was from the student, 7 (30.4%),
EMS 7 (30.4%), school 7(30.4%), and unknown 2(8.7%). A majority (21, 91.3%) of
the public school cases occurred in communities with ALS systems and ALS response
was relatively rapid (median response 6 minutes, 90 percentile, 13 minutes). The
unsubsidized annual cost of Michigan public schools to stock EAIs ranges from
$565,460 to $4,846,800. CONCLUSION: In this study, few public school patients
received epinephrine for anaphylaxis and the vast majority occurred in
communities with rapid ALS response. The direct annual supply cost of the school
EAI mandate is substantial.
PMID- 28414560
TI - Aloe arborescens Polysaccharides: In Vitro Immunomodulation and Potential
Cytotoxic Activity.
AB - Different polysaccharides were isolated from the leaves of Aloe arborescens using
the gradient power of hydrogen followed by antitumor and immunomodulatory assay.
The total polysaccharide content of different fractions, water-soluble
polysaccharide (WAP), acid-soluble polysaccharide (ACP), and alkaline-soluble
polysaccharide (ALP), was estimated using a phenol-sulfuric acid
spectrophotometric method. WAP possessed a higher content of mannose and glucose
than either ACP or ALP. In vitro antitumor activity was investigated in three
different cancer cell lines, and in vitro immunomodulatory potential was assessed
through phagocytosis and lymphocyte transformation assay. The results showed that
WAP and ALP exhibited the most significant cytotoxicity against HepG2 human liver
cancer cells, with IC50 values of 26.14 and 21.46 MUg/mL, respectively. In
contrast, ALP was able to enhance lymphocyte transformation, whereas WAP had the
most potent phagocytic activity. Molecular weight, total sugar and uronic acid
content, Fourier transform-infrared analysis, and linkage type of bioactive
polysaccharides were investigated. These findings revealed that the potential
antitumor activity of the natural agents WAP and ALP was through an
immunomodulation mechanism, which verifies the use of the plant as adjuvant
supplement for cancer patients suffering immunosuppression during chemotherapy.
PMID- 28414561
TI - Interferon Alpha for the Treatment of Cystoid Macular Edema Associated with
Presumed Ocular Tuberculosis.
AB - PURPOSE: To report the efficacy and safety of interferon (IFN) alpha-2a in
patients with cystoid macular edema (CME) associated with presumed ocular
tuberculosis (TB). METHODS: We reviewed the clinical records of 5 patients with
presumed ocular TB who had been treated with IFN alpha-2a for recurrent CME
during or after completion of anti-tubercular therapy. IFN alpha-2a was
administered at an initial dose of 3 million IU per day and then tapered after
the initial response. Treatment efficacy was assessed by central macular
thickness (CMT) measurement using spectral-domain optical coherence tomography
and visual acuity. RESULTS: Three patients were men, and 2 were women. Patients
were aged between 38 and 66 years. Mean CMT was 483 +/- 178.6 MUm at baseline,
302.3 +/- 56 MUm at 1 week, 312.3 +/- 49.5 MUm at 1 month, and 286.2 +/- 31.9 MUm
at 3 months. Mean LogMAR visual acuity was 0.6 +/- 0.4 at baseline, 0.4 +/- 0.3
MUm at 1 week, 0.3 +/- 0.3 at 1 month, and 0.3 +/- 0.3 at 3 months. The treatment
was interrupted for 10 days because of neutropenia after 2 weeks in 1 patient and
discontinued in another after 10 days because of intolerance. Total treatment
duration was 3-24 months in the remaining 4 patients. CONCLUSION: The present
small case series suggests that IFN alpha-2a may be an effective and safe
therapeutic option for CME that is associated with presumed ocular TB.
PMID- 28414562
TI - A Review of Cochrane Systematic Reviews of Interventions Relevant to Orthoptic
Practice.
AB - AIM: To present an overview of the range of systematic reviews on intervention
trials pertinent to orthoptic practice, produced by the Cochrane Eyes and Vision
group (CEV). METHODS: We searched the 2016 Cochrane Library database (31.03.2016)
to identify completed reviews and protocols of direct relevance to orthoptic
practice. These reviews are currently completed and published, available on
www.thecochranelibrary.com (free to UK health employees) or via the CEV website
(http://eyes.cochrane.org/) . RESULTS: We found 27 completed CEV reviews across
the topics of strabismus, amblyopia, refractive errors, and low vision. Seven
completed CEV protocols addressed topics of strabismus, amblyopia, refractive
errors, low vision, and screening. We found 3 completed Cochrane Stroke reviews
addressing visual field loss, eye movement impairment, and age-related vision
loss. CONCLUSIONS: The systematic review process presents an important
opportunity for any clinician to contribute to the establishment of reliable,
evidence-based orthoptic practice. Each review has an abstract and plain language
summary that many non-clinicians find useful, followed by a full copy of the
review (background, objectives, methods, results, discussion) with a conclusion
section that is divided into implications for practice and implications for
research. The current reviews provide patients/parents/carers with information
about various different conditions and treatment options, but also provide
clinicians with a summary of the available evidence on interventions, to use as a
guide for both clinical practice and future research planning. The reviews
identified in this overview highlight the evidence available for effective
interventions for strabismus, amblyopia, refractive errors, and low vision or
stroke rehabilitation as well as the gaps in the evidence base. Thus, a demand
exists for future robust, randomized, controlled trials of such interventions of
importance in orthoptic practice.
PMID- 28414563
TI - Leveraging Stem Cell Homing for Therapeutic Regeneration.
AB - Resident stem cell pools in many tissues/organs are responsible not only for
tissue maintenance during physiologic turnover but also for the process of wound
repair following injury. With inspiration from stem cell trafficking within the
body under physiologic and pathologic conditions, recent advances have been made
toward inducing stem cell mobilization and directing patients' own cells to sites
of interest for treating a broad spectrum of diseases. An evolving body of work
corroborates that delivering guidance cues can mobilize stem cells from the bone
marrow and drive these cells toward a specific region. In addition, the
transplantation of cell-friendly biomaterials incorporating certain biomolecules
has led to the regeneration of lost/damaged tissue without the need for
delivering cellular materials manipulated ex vivo. Recently, cell homing has
resulted in remarkable biological discoveries in the laboratory as well as great
curative successes in preclinical scenarios. Here, we review the biological
evidence underlying in vivo cell mobilization and homing with the aim of
leveraging endogenous reparative cells for therapeutic applications. Considering
both the promise and the obstacles of this approach, we discuss how matrix
components of the in vivo milieu can be modified to promote the native
regenerative process and inspire future tissue-engineering design.
PMID- 28414564
TI - Tivantinib for the treatment of hepatocellular carcinoma.
AB - INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the leading causes of
cancer-related death worldwide with a poor prognosis due to late diagnosis in the
majority of cases. Physicians are frequently confronted with patients who are not
eligible for curative or locoregional treatments any more. In this scenario, the
multi-tyrosine kinase inhibitor sorafenib remains the only systemic first-line
treatment option providing modest survival benefit compared to placebo with
significant but for most patients acceptable adverse effects. Areas covered:
Tivantinib was the first antiproliferative agent to be been applied in a phase
III trial based on receptor overexpression analyses after disease progression on
sorafenib. While phase I and II trials with tivantinib in second line showed
encouraging results, a recent press release announced that the METIV-HCC phase
III study of tivantinib in HCC did not meet its primary endpoint of improving
overall survival. Expert commentary: Evidence for antiangiogenetic therapy
inducing tumor hypoxia leading to overexpression of proliferative genes,
including cMET, underlines the potential of tivantinib as second-line treatment.
However, as the mechanism of action of tivantinib through cMET inhibition has
recently been questioned by several groups, identification of alternative
proliferative markers or targets is mandatory.
PMID- 28414565
TI - New Regenerative Vascular Grafts for Hemodialysis Access: Evaluation of a
Preclinical Animal Model.
AB - The purpose of this study was to evaluate a suitable animal model for the in vivo
evaluation of patency and vascular tissue regeneration in small intestinal
submucosa (SIS) vascular grafts for hemodialysis access. First, a 4-mm U-shaped
SIS vascular graft was implanted between the internal carotid artery (CA) and the
external jugular vein (JV) in five sheep and six swine. The U-shape grafts
remained functional for 53 +/- 4 days in sheep and 32 +/- 2 days in swine. The
sheep model presented exaggerated inflammation, so the swine model was selected
for the in vivo study. Based on these initial results, a 4-mm C-shape SIS
vascular graft with SIS circumferential reinforcement was developed to
mechanically improve the vascular graft and manage complications identified
during surgery in both sheep and swine. The C-shape vascular graft was implanted
in a swine model (n = 3) between the CA and JV. GORE-TEX(r) vascular grafts were
used as controls in the contralateral side of the neck. C-shape grafts remained
patent for 47 +/- 4 days, whereas the GORE-TEX(r) grafts were patent for 30 +/-
15 days. The C-shape vascular graft was easier to handle during surgery, and its
circumferential reinforcement improved in vivo patency, avoiding kinks in the
graft after implantation. Histological results showed neovascularization and some
regeneration with the alignment of endothelial cells in the vascular wall of the
grafts. The model developed may be helpful in other research involving in vivo
studies of vascular grafts for hemodialysis access.
PMID- 28414566
TI - The Changed Proportion of CD45RA+/CD45RO+ T Cells in Chronic Hepatitis C Patients
During Pegylated Interferon-alpha with Ribavirin Therapy.
AB - Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis,
liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV
infection is the combination of pegylated interferon-alpha with ribavirin, which
increases the rate of sustained virological response (SVR) to 56%. However, a
practical biomarker to predict SVR is lacking. T cells expressing the CD45RA
isoform are considered naive, and antigenic stimulation converts them to CD45RO+.
CD45RO+ T cells exhibit immediate response and high lymphokine production,
leading to the maintenance and upregulation of immune reactions. The aim of this
study is to clarify the proportions of CD45RA+ and CD45RO+ T cells associated
with rapid virological response and SVR. We collected blood samples from 32 HCV
patients receiving the combined treatment. The samples were collected before,
during 4th, 12th, and 24th therapy weeks, and 4th week posttherapy, and their T
cell populations were analyzed using flow cytometry. Twenty-nine patients (90.6%)
achieved SVR. There were significant declines in proportions of CD45RA+ cells
during 4th, 12th, and 24th therapy weeks, and significant increases in
proportions of CD45RO+ cells during 24th therapy week and 4th week posttherapy (P
< 0.05). Patients undergoing hepatitis C therapy exhibited lowered CD45RA+ cell
proportions and increased CD45RO+ cell proportions. This effect may be important
in a patient's response to pegylated interferon-alpha with ribavirin therapy.
PMID- 28414567
TI - Disease burden of community acquired pneumonia among children under 5 y old in
China: A population based survey.
AB - BACKGROUND: To obtain the baseline data on the incidence and cost of community
acquired pneumonia among under-5 children for future studies, and provide
evidence for shaping China's strategies regarding pneumococcal conjugate vaccine
(PCV). METHODS: Three townships from Heilongjiang, Hebei and Gansu Province and
one community in Shanghai were selected as study areas. A questionnaire survey
was conducted to collect data on incidence and cost of pneumonia among children
under 5 y old in 2012. RESULTS: The overall incidence of clinically diagnosed
pneumonia in children under 5 y old was 2.55%. The incidence in urban area was
7.97%, higher than that in rural areas (1.68%). However, no difference was found
in the incidences of chest X-ray confirmed pneumonia between urban and rural
areas (1.67% vs 1.23%). X-ray confirmed cases in rural and urban areas
respectively accounted for 73.45% and 20.93% of all clinically diagnosed
pneumonia. The hospitalization rate of all cases was 1.40%. Incidence and
hospitalization rate of pneumonia decreased with age, with the highest rates
found among children younger than one year and the lowest among children aged 4
(incidence: 4.25% vs 0.83%; hospitalization: 2.75% vs 0.36%). The incidence was
slightly higher among boys (2.92% vs 2.08%). The total cost due to pneumonia for
the participants was 1138 733 CNY. The average cost and median cost was 5722 CNY
and 3540 CNY separately. Multivariate analysis showed that the only factor
related to higher cost was hospitalization. CONCLUSIONS: The disease burden was
high for children under 5 y old, especially the infant. PCV has not been widely
used among children, and thus further health economics evaluation on introducing
PCV into National Immunization Program should be conducted.
PMID- 28414568
TI - Moving Beyond Traditional Cardiovascular Risk Factors Toward Gendered Horizon.
PMID- 28414569
TI - Elevated Levels of Plasma Mitochondrial DNA Are Associated with Clinical Outcome
in Intra-Abdominal Infections Caused by Severe Trauma.
AB - BACKGROUND: The purpose of our study was to determine prospectively relationships
between plasma mitochondrial deoxyribonucleic acid (mtDNA) concentration and
clinical outcome in patients with intra-abdominal infections (IAIs) induced by
severe abdominal trauma. PATIENTS AND METHODS: The DNA was isolated from serum
samples taken from patients with IAIs at hospital days zero, one, and two. Plasma
mtDNA concentration was assessed by real-time polymerase chain reaction (PCR).
The study population's clinical and laboratory data were analyzed. RESULTS: The
mtDNA damage-associated molecular patterns were expressed as a PCR threshold
cycle number using four selected sequences. The patients with IAIs had
significant higher plasma mtDNA than healthy control subjects. Patients with IAIs
with sepsis apparently had elevated mtDNA levels compared with non-septic
patients with IAIs (30.9 +/- 2.0 vs. 28.7 +/- 2.4; 33.3 +/- 2.6 vs. 28.9 +/- 2.4;
32.9 +/- 1.6 vs. 31.2 +/- 2.2; 33.1 +/- 3.6 vs. 28.1 +/- 2.2, respectively).
Patients with IAIs in whom multiple organ dysfunction syndrome (MODS) developed
also had increased mtDNA concentration compared with those who did not (31.0 +/-
1.8 vs. 27.9 +/- 1.8; 32.9 +/- 2.4 vs. 27.8 +/- 1.7; 32.9 +/- 1.5 vs. 29.8 +/-
1.7; 32.0 +/- 3.8 vs. 27.1 +/- 2.1, respectively). Baseline mtDNA concentration
had high effectiveness in predicting death for patients with IAIs who had severe
trauma using receiver operating characteristic analysis. Furthermore, serum mtDNA
levels on admission correlated with the lactate concentration, but no significant
correlations were found between mtDNA levels and levels of white blood cells, C
reactive protein, and procalcitonin. CONCLUSIONS: Plasma mtDNA was associated
with the occurrence of sepsis, MODS, and death in patients with IAIs caused by
severe abdominal trauma.
PMID- 28414570
TI - Perceived Stress in Online Prostate Cancer Community Participants: Examining
Relationships with Stigmatization, Social Support Network Preference, and Social
Support Seeking.
AB - Men with prostate cancer often need social support to help them cope with illness
related physiological and psychosocial challenges. Whether those needs are met
depends on receiving support optimally matched to their needs. This study
examined relationships between perceived stress, prostate cancer-related stigma,
weak-tie support preference, and online community use for social support in a
survey of online prostate cancer community participants (n = 149). Findings
revealed a positive relationship between stigma and perceived stress. This
relationship, however, was moderated by weak-tie support preference and online
community use for social support. Specifically, stigma was positively related to
perceived stress when weak-tie support was preferred. Analyses also showed a
positive relationship between stigma and perceived stress in those who used their
online community for advice or emotional support. Health communication scholars
should work collaboratively with diagnosed men, clinicians, and online community
administrators to develop online interventions that optimally match social
support needs.
PMID- 28414571
TI - The Novel Technique of Transabdominal Preperitoneal Hernioplasty Herniorrhaphy
for Direct Inguinal Hernia: Suture Repair of Hernia Defect Wall.
AB - BACKGROUND: Conventional laparoscopic surgeries of direct inguinal hernia include
two methods, transabdominal preperitoneal hernioplasty (TAPP) and totally
extraperitoneal hernioplasty. Both methods are performed using synthetic mesh
without suturing the hernia defect and require extensive mesh coverage for not
only Hesselbach's triangle but also indirect ring. For minimally invasive
operation, suture of direct hernia defect was devised and performed. The purpose
of this study is to evaluate the efficacy of defect wall suture of laparoscopic
herniorrhaphy for direct inguinal hernia patients. METHODS: We evaluated 210
direct inguinal hernia patients who received TAPP in Damsoyu Hospital, Seoul,
Republic of Korea from September 2012 to December 2015. The patients were
categorized into two groups according to TAPP techniques; cTAPP group had
conventional TAPP without defect wall suture, and rTAPP group had defect wall
suture TAPP. There were 99 patients in a cTAPP group and 111 patients in rTAPP
group. RESULTS: Operation time and postoperative hospital stay showed no
difference between two groups. The postoperative pain score within the first week
was significantly lower in rTAPP group than in cTAPP group (P < .001). The mean
timing of a return to normal activities for rTAPP group was 3.8 days, which was
shorter than 4.6 days of cTAPP group (P < .001). There was no difference in
complication and recurrence rates between two groups. CONCLUSIONS: Defect wall
suture for direct inguinal hernia had shorter operation time, faster recovery
time, reduced pain, and an acceptable rate of recurrence and complication. This
TAPP surgery with hernia defect wall suture that requires smaller dissection area
is an effective method for treating direct inguinal hernia.
PMID- 28414572
TI - Molecular Characterization of Fluoroquinolone-Resistant Haemophilus
parainfluenzae Clinical Isolates in Spain.
AB - OBJECTIVE: The objective was to characterize a group of clinical isolates of
fluoroquinolone-resistant Haemophilus parainfluenzae collected in Northern Spain
(March-December 2014). METHODS: Twelve clinical isolates of H. parainfluenzae
were studied by performing antimicrobial susceptibility testing and PCR
amplification and nucleotide sequencing of the QRDR (quinolone resistance
determining region) of gyrA, parC, gyrB, and parE genes. Screening for plasmid
mediated quinolone resistance (PMQR) was also studied. Pulsed-field gel
electrophoresis (PFGE) was used for molecular typing. RESULTS: Antimicrobial
susceptibility testing showed that all the isolates were resistant to the
fluoroquinolones tested (ciprofloxacin, levofloxacin, norfloxacin, and
moxifloxacin). Analysis of the QRDR demonstrated that all the isolates presented
mutations in gyrA and parC. A Glu88Lys substitution in ParC is reported for the
first time in H. parainfluenzae. No PMQR gene was detected. PFGE results showed
that isolates were not clonally related. CONCLUSION: Multiple H. parainfluenzae
fluoroquinolone-resistant isolates grouped in the same area in a short period of
time showed diverse substitutions in QRDR of gyrA/parC and were not clonally
related, indicating individual emergence. In addition, we described the first
report of Glu88Lys substitution in ParC.
PMID- 28414573
TI - Phosphatidylserine Translocation after Radiosurgery in an Animal Model of
Arteriovenous Malformation.
AB - Phosphatidylserine (PS) is asymmetrically distributed across the plasma membrane,
located predominantly on the inner leaflet in healthy cells. Translocation of PS
to the outer leaflet makes it available as a target for biological therapies. We
examined PS translocation after radiosurgery in an animal model of brain
arteriovenous malformation (AVM). An arteriovenous fistula was created by end-to
side anastomosis of the left external jugular vein to the common carotid artery
in 6-week-old, male Sprague Dawley rats. Six weeks after AVM creation, 15 rats
underwent Gamma Knife stereotactic radiosurgery receiving a single 15 Gy dose to
the margin of the fistula; 15 rats received sham treatment. Externalization of PS
was examined by intravenous injection of a PS-specific near-infrared probe, PSVue
794, and in vivo fluorescence optical imaging at 1, 7, 21, 42, 63 and 84 days
postirradiation. Fluorescent signaling indicative of PS translocation to the
luminal cell surface accumulated in the AVM region, in both irradiated and
nonirradiated animals, at all time points. Fluorescence was localized
specifically to the AVM region and was not present in any other anatomical sites.
Translocated PS increased over time in irradiated rats (P < 0.001) but not in
sham-irradiated rats and this difference reached statistical significance at day
84 (P < 0.05). In summary, vessels within the mature rat AVM demonstrate elevated
PS externalization compared to normal vessels. A single dose of ionizing
radiation can increase PS externalization in a time-dependent manner. Strict
localization of PS externalization within the AVM region suggests that
stereotactic radiosurgery can serve as an effective priming agent and PS may be a
suitable candidate for vascular-targeting approaches to AVM treatment.
PMID- 28414574
TI - Examining Acceptability of Self-Collection for Human Papillomavirus Testing Among
Women and Healthcare Providers with a Broader Lens.
PMID- 28414575
TI - Prevalence of Violence Toward Community Nurses: A Questionnaire Survey.
AB - Violence toward nursing staff occurs frequently, particularly in intensive care
units and closed or intensive psychiatric facilities, which have been studied
previously. However, violence toward community nurses has not been investigated.
The purpose of this study was to explore the frequency of violence toward
community nurses in Slovenia. More than 56% of study respondents were verbally
abused by their patients during the past year. More than 42% of all cases of
horizontal violence were directed at community nurses.
PMID- 28414576
TI - HCBS Spending and Nursing Home Admissions for 1915(c) Waiver Enrollees.
AB - Medicaid waiver programs for home- and community-based services (HCBS) have grown
rapidly and serve a population at high risk for nursing home (NH) admission. This
study utilized the Medicaid Analytic Extract Personal Summary File and the NH
Minimum Data Set and tested whether higher levels of per-beneficiary HCBS
spending were associated with (1) lower risk of long-term (90+ days) NH admission
and (2) higher functional/cognitive impairment at admission for new enrollees in
1915(c) aged or aged and disabled waiver programs. Waiver enrollees in states and
counties with higher HCBS spending were found to have lower risk of long-term NH
admission and greater functional impairment at NH admission compared to waiver
enrollees in states and counties with lower spending. This indicates that higher
per-enrollee HCBS spending may enable waiver enrollees to remain in the community
until their functional impairment becomes more severe.
PMID- 28414577
TI - Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg
Negative Chronic Viral Hepatitis B.
AB - Toll-like receptors (TLRs) may play an important role in hepatitis-B
pathogenesis. However, serum TLR-2 and TLR-4 levels and their association with
serum liver enzymes, hepatitis B virus (HBV) DNA, quantitative HBsAg levels, and
liver biopsy findings, are unknown. A total of naive 40 HBeAg (-) chronic
hepatitis B (CHB) patients and 20 healthy control subjects were recruited in this
study. Liver tests, HBV DNA, serum TLR-2 and TLR-4, and quantitative HBsAg levels
were evaluated among all groups. The relationship among TLR-2, TLR-4,
quantitative HBsAg levels and liver tests, and liver histological findings were
investigated with correlation analysis. Serum TLR-2 and TLR-4 levels in HBeAg (-)
CHB patients were higher than in the control group. There was a positive
correlation between serum TLR-2, TLR-4, and HBV DNA and ALT levels. We have
further demonstrated that serum TLR-2 levels are correlated with AST and
quantitative HBsAg levels. However, TLRs levels were not linked to the liver
biopsy findings. TLR can have an important role in hepatitis B pathogenesis.
Liver injury in CHB may cause elevated TLR-2 and TLR-4 levels.
PMID- 28414578
TI - The Impact of In-Home Services Utilization on the Institutionalization of Older
People in Korea.
AB - As a result of aging populations, institutionalization of older people is
creating an increasing financial burden in many countries. The purpose of the
present study was to explore the impact of in-home service utilization on
institutionalization. The subjects were newly certified as eligible for long-term
care insurance between January and February 2009 in Korea. The follow-up period
was 40 months, to April 2012. We used logistic regression models to identify
factors influencing the transition to institutional service, adjusting for
gender, age, living status, income level, activities of daily living, and chronic
disease. The institutionalization rate was estimated to be 17.3% over 40 months.
The interval from transitional living to institutionalization was 36 +/- 8
months. Risk factors of transition to institutional services are being female,
having advanced age, living with friends or cousins, getting dementia, and not
using in-home services. We determined that institutionalization is mitigated by
use of in-home services. Therefore, supplying appropriate in-home services to
current nonusers would help to greatly reduce the rate of institutionalization of
older people.
PMID- 28414579
TI - Housing First for Adults with Problematic Substance Use.
AB - OBJECTIVES: This study explores the two-year housing- and non-housing-related
outcomes for adults who are homeless with problematic substance use who received
scattered-site housing and intensive case management services from a Housing
First program in Ottawa, Canada, in comparison with a group of adults who are
homeless with problematic substance use who had access to standard care in the
community. METHODS: Housing First clients (n = 89) and members of a comparison
group (n = 89) completed structured interviews at baseline and were followed for
two years. RESULTS: Housing First clients moved into housing more quickly,
reported a greater proportion of time housed, were more likely to spend the final
six months housed, and had longer housing tenure at 24 months. There was a group
by time interaction on problematic alcohol use with more rapid improvement for
the comparison group; however, both groups improved over time. The comparison
group had a greater decrease on problematic drug use by 24 months. There was no
change in physical health and only the comparison group had improvements in
mental health by 24 months. The groups had similar improvement on community
functioning by 24 months. The comparison group had a greater increase in total
quality of life. More specifically, the comparison group had an increase in the
family relations-related quality of life, whereas the clients did not. There was
a significant interaction for safety-related quality of life, but both groups
experienced improvements over time and had comparable levels of satisfaction with
safety at each time point. The Housing First clients reported higher levels of
satisfaction with living conditions than the comparison group at baseline and 12
months, but not at 24 months. There was significant improvement over time and no
main effect of group for finances, leisure, and social relations. CONCLUSIONS:
Adults who are homeless with problematic substance use can successfully be housed
using a Housing First approach. However, further targeted services might be
required to address other areas of functioning, such as health, substance use,
and quality of life.
PMID- 28414580
TI - Identifying Personal Risk Factors for Falls in the Workplace.
AB - Falls can occur in any occupational setting. Occupational health professionals
may focus on creating a safe work environment and training programs to prevent
falls. However, an important aspect of safety management is identifying at-risk
employees. The purpose of this article is to identify personal risk factors and
offer interventions to prevent falls in the workplace.
PMID- 28414581
TI - Posttraumatic growth after cancer: The role of perceived threat and cognitive
processing.
AB - This study examines the relation between perceived cognitive and physical threat
after a cancer diagnosis and posttraumatic growth (PTG). In total, 169 breast,
prostate, and colorectal cancer survivors completed questionnaires. Hierarchical
regression models found after controlling for demographic and medical variables,
depression, anxiety, and perceived threat account for 41.8% of the variance of
positive cognitive processing, and these variables along with positive cognitive
processing accounted for 42.7% of the variance of PTG. Positive cognitive
processing mediated the pathways between perceived physical threat and PTG.
Cognitive processing appears to play a key role in the emergence of PTG following
cancer. By exploring survivors' cognitions and perceived threat, psychosocial
providers may help cancer survivors cultivate PTG.
PMID- 28414582
TI - Educating the next generation of family caregivers through the use of dynamic
case studies.
AB - Between 2008 and 2016, students in an Introduction to Gerontology course were
required to complete a dynamic case study project simulating caregiving
arrangement decision making. Students were divided into groups representing
typical multigenerational families and were required to determine how to develop
caregiving arrangements to respond to an older family member' s changing levels
of need. The assignment concluded with students writing a final paper summarizing
what they learned. This study examined the themes emerging from student group
case study papers to gain an understanding of the challenges students face in
understanding the dynamics of making family-based caregiving decisions. This is
of particular importance as many students were seeking careers in human services
and would be assisting clients in such decision-making processes, as well as
involvement in decision making for their own family members. Themes that emerged
from group papers and the implications related to gerontology education and
policy are discussed.
PMID- 28414584
TI - Screening Commercial Vehicle Drivers for Obstructive Sleep Apnea: Tools,
Barriers, and Recommendations.
AB - Obstructive sleep apnea (OSA) is a disorder characterized by a cessation of
breathing during sleep, leading to poor sleep patterns and daytime somnolence.
Daytime somnolence is of particular concern for commercial vehicle drivers, whose
crash risk increases 50% with untreated OSA. The process of diagnosing and
treating OSA in commercial drivers begins with effective and consistent
screening. Therefore, the researchers screened drivers with both the STOP-Bang
Questionnaire and the Obstructive Sleep Apnea Evaluation Worksheet (OSAEW) and
compared the two tools. Drivers screening positive on the STOP-Bang
Questionnaire, OSAEW, and both questionnaires were 28%, 23%, and 13%,
respectively. Sleep study referrals were made for 50 drivers; 12 drivers were
scheduled for sleep tests within 3 months. Health care provider referral rates
for drivers screening at high risk (37%) and commercial driver monitoring rates
(24%) were both low. Recommendations to improve OSA screening and testing
practices include Federal Motor Carrier Safety Administration-mandated screening
and referral guidelines, employee-facilitated sleep testing, and OSA awareness
campaigns.
PMID- 28414583
TI - Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking
Cessation Attempt with Varenicline and Behavioral Therapy.
AB - OBJECTIVE: Smoking prevalence rates are elevated in individuals with
schizophrenia spectrum disorders (SSD) compared with the general population, with
attendant disproportionate smoking-related morbidity and mortality.
Pharmacotherapies that improve abstinence rates in this population are
underutilized, partly due to concerns about neuropsychiatric safety, particularly
for those with comorbid depression or prior suicide attempt. Prospective
assessment of the psychiatric safety profile of varenicline in those with SSD is
needed. METHODS: Adult smokers with SSD entered a 12-week trial of varenicline
and behavioral therapy for smoking cessation. Depressive symptoms were assessed
with the Calgary Depression Scale for Schizophrenia (CDSS) at baseline and weekly
thereafter. Participants with baseline and one or more postbaseline CDSS
assessments, n = 179, were included in a secondary analysis of change in
depressive symptoms with varenicline treatment, adjusting for abstinence status
and baseline depressive symptoms. RESULTS: Twenty-seven percent of participants
had a CDSS score at baseline consistent with current major depressive disorder,
and more than half had a prior suicide attempt. Forty-one percent (74/179)
achieved two or more weeks of continuous abstinence at the end of treatment. CDSS
scores declined 31% during the 12-week treatment period. Controlling for baseline
CDSS scores, depressive symptoms declined over time in those who completed the
trial, independent of abstinence status, and either declined or remained
unchanged in those with major depressive disorder or prior suicide attempt or who
were taking antidepressant medication. Those who did not complete the trial had
no change in depressive symptoms. DISCUSSION: Depressive symptoms declined in
adults with schizophrenia during 12 weeks of varenicline treatment and cognitive
behavioral therapy, independent of tobacco abstinence. Smokers with SSD who have
significant depressive symptoms may be successful in smoking cessation attempts
with pharmacotherapeutic aids such as varenicline while maintaining stable
psychiatric symptoms. This is a secondary analysis of data collected as part of a
clinical trial registered as NCT00621777, at www.clinicaltrials.gov .
PMID- 28414585
TI - Race, Language, or Length of Residency? Explaining Unequal Uptake of Government
Pensions in Canada.
AB - Canada's old age security (OAS), a flat-benefit public pension, is
internationally lauded as an accessible and effective safety net for seniors.
This paper explores discrepancies in OAS uptake using Canadian Census data from
1996 to 2011. Our findings demonstrate disparities in OAS uptake based on
immigration status, language proficiency, and visible minority status, disputing
claims of "universal" OAS provision. Multivariate analyses confirm a strong
"immigrant effect," with being in Canada for 20 years or less leading to lower
rates of OAS utilization. They also confirm that those not proficient in Canada's
official languages are less likely to receive OAS benefits. However, the
influence of racialized minority status is found to be spurious; after
controlling for immigration status and official language proficiency, many
racialized minority senior groups have higher odds of receiving OAS than White
Canadians. We conclude with a brief discussion of the tradeoffs involved in
considering a potential removal of OAS eligibility barriers for immigrants in
Canada.
PMID- 28414587
TI - Non-melanoma skin cancer: new and future synthetic drug treatments.
AB - INTRODUCTION: Non-melanoma skin cancers (NMSC) mainly comprise two different
entities: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); beneath
these two entities, Merkel cell carcinoma, adnexal tumors, dermatofibrosarcoma
protuberans, angiosarcoma, and cutaneous lymphoma belong to NMSC. These rare skin
tumors are not the topic of this review. BCC and SCC are the most common cancers
diagnosed in humans. The preferred treatment is surgery, which in most cases is
curative. Although a high recurrence rate is seen, these cancers rarely
metastasize. Therefore, systemic treatments were not a priority for these
patients. It is long known that the abnormal activation of Hedgehog and epidermal
growth factor receptor pathways were involved in BCC and SCC. In the last decade,
metastatic disease became an important area of research, mostly because new
therapies that targeted components of these two pathways became available. Areas
covered: Here we cover the available therapeutic options for patients diagnosed
with BCC and SCC, focus on systemic and targeted therapies. Expert opinion: BCC
and SCC are common cancers, with good prognosis. More than the metastatic
disease, advanced local disease and recurrent disease pose clinicians a great
challenge. Albeit there are promising results with targeted therapies, resistance
development has already been described.
PMID- 28414586
TI - Development and Validation of Monoclonal Antibody-Based Antigen Capture ELISA for
Detection of Group A Porcine Rotavirus.
AB - Porcine rotavirus-A (PoRVA) is one of the common causes of mild to severe
dehydrating diarrhea, leading to losses in weaning and postweaning piglets. A
rapid, highly specific, and sensitive antigen-capture enzyme-linked immunosorbent
assay (AC-ELISA) was developed for detection of PoRVA, by using VP6 (a highly
conserved and antigenic protein of group-A rotavirus)-directed rabbit polyclonal
antibodies (capture antibody) and murine monoclonal antibodies (detector
antibody). The detection limit of AC-ELISA was found to be equal to that of
conventional reverse transcription-polymerase chain reaction (RT-PCR; about 102.5
TCID50/mL). For validation of the in-house AC-ELISA, 295 porcine fecal/diarrhea
samples, collected from different provinces of China, were evaluated and compared
with conventional RT-PCR and TaqMan RT-quantitative PCR (qPCR). The sensitivity
and specificity of this in-house AC-ELISA relative to RT-qPCR were found to be
91.67% and 100%, respectively, with the strong agreement (kappa = 0.972) between
these two techniques. Total detection rate with AC-ELISA, conventional RT-PCR,
and RT-qPCR were found to be 11.2%, 11.5%, and 12.2%, respectively, without any
statistical significant difference. Moreover, AC-ELISA failed to detect any cross
reactivity with porcine epidemic diarrhea virus, transmissible gastroenteritis
virus, pseudorabies virus, and porcine circovirus-2. These results suggested that
our developed method was rapid, highly specific, and sensitive, which may help in
large-scale surveillance, timely detection, and preventive control of rotavirus
infection in porcine farms.
PMID- 28414588
TI - Prehospital Predictors of Traumatic Spinal Cord Injury in Victoria, Australia.
AB - OBJECTIVES: To identify the predictors of traumatic spinal cord injury (TSCI) and
describe the differences between confirmed and potential TSCI cases in the
prehospital setting. METHODS: A retrospective cohort study including all adult
patients over a six-year period (2007-12) with potential TSCI who were attended
and transported by Ambulance Victoria (AV). We extracted potential TSCI cases
from the AV data warehouse and linked with the Victorian State Trauma Registry to
compare with final hospital diagnosis. RESULTS: We included a total of 106,059
patients with potential TSCI in the study, with 257 having a spinal cord injury
confirmed at hospital (0.2%). The median [First and third Quartiles] age of
confirmed TSCI cases was 49 [32-69] years, with males comprising 84.1%. Confirmed
TSCI were mainly due to falls (44.8%) and traffic incidents (40.5%). AV spinal
care guidelines had a sensitivity of 100% to detect confirmed TSCI. There were
several factors associated with a diagnosis of TSCI. These were meeting AV
Potential Major Trauma criteria, male gender, presence of neurological deficit,
presence of an altered state of consciousness, high falls (> 3 meters), diving,
or motorcycle or bicycle collisions. CONCLUSION: This study identified several
predictors of TSCI including meeting AV Potential Major Trauma criteria, male
gender, presence of neurological deficit, presence of an altered state of
consciousness, high falls (> 3 meters), diving, or motorcycle or bicycle
collisions. Most of these predictors are included in NEXUS and/or CCR criteria,
however, Potential Major Trauma criteria have not previously been linked to the
presence of TSCI. Therefore, Emergency Medical Systems are encouraged to
integrate similar Potential Major Trauma criteria into their guidelines and
protocols to further improve the provider's accuracy in identifying TSCI and to
be more selective in their spinal immobilization, thereby reducing unwarranted
adverse effects of this practice.
PMID- 28414589
TI - Progesterone Decreases in vitro Indoleamine 2, 3-dioxygenase Expression in
Dendritic and CD4+ Cells from Maternal-Fetal Interface of Rats.
AB - PROBLEM: Several mechanisms contribute to the tolerogenic state observed during
pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO).
This initializes the catabolism of tryptophan, inducing T cells to apoptosis due
to its deprivation and by the action of its catabolites in the placental
microenvironment. Progesterone plays an important part on immunological tolerance
mechanisms during pregnancy; however, there is no evidence it is related to IDO
activity. Thus, this study aimed to investigate progesterone influence on the
maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive
cells by immunophenotyping and flow cytometry under exogenous progesterone
supplementation. METHOD OF STUDY: Placenta and embryo cells were cultured and
separated into groups that received interferon gamma or progesterone,
supplemented or not with mifepristone. After 2 and 24 h, these were labeled with
an anti-IDO and a series of antibodies specific to leucocytes and progesterone
receptor and processed through flow cytometry analysis. RESULTS: Progesterone
induced a significant decrease in the expression of IDO in dendritic cells and
CD4+ lymphocytes. CONCLUSION: The blocking of progesterone receptor on these
cells by mifepristone restored IDO expression levels and may constitute evidence
of the participation of this hormone through a direct route in these cells.
PMID- 28414590
TI - Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery
Disease.
AB - BACKGROUND: Natural killer (NK) cells are the potential modulators of
inflammatory reactions that exert several unique biological effects and could
lead to future adverse events of coronary artery disease (CAD). HYPOTHESIS: The
purpose of this study was to find out the possible association of modulation in
NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-alpha)
in CAD patients and various forms of myocardial infarction. METHODS: The present
study included total 190 subjects (98 confirmed CAD patients both men and women
and 92 healthy control individuals). Serum concentration of TNF-alpha was
measured by ELISA method. For the measurement of various immune cells, viz., NK
cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed.
RESULTS: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was
observed in CAD patients. Moreover, non-ST segment elevation myocardial
infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable
angina (UA), and combined UA + NSTEMI group also showed a significant decline in
NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a
significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA +
NSTEMI group did not show any significant change in TNK cells. On the other hand,
the level of TNF-alpha was found to be significantly elevated in CAD, STEMI, and
UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant
change in TNF-alpha level. CONCLUSION: Current study provides an insight toward
the association of immune cells and inflammation with CAD.
PMID- 28414592
TI - Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the
Eye.
AB - Diadenosine tetraphosphate abbreviated Ap4A is a naturally occurring
dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic
resistance to enzyme degradation compared to mononucleotides, this molecule can
exhibit profound actions on ocular tissues, including the ocular surface, ciliary
body, trabecular meshwork, and probably the retina. The actions of Ap4A are
mostly carried out by P2Y2 receptors, but the participation of P2X2 and P2Y6 in
processes such as the regulation of intraocular pressure (IOP), together with the
P2Y2, is pivotal. Beyond the physiological role, this dinucleotide can present on
the ocular surface keeping a right production of tear secretion or regulating
IOP. It is important to note that exogenous application of Ap4A to cells or
animal models can significantly modify pathophysiological conditions and thus is
an attractive therapeutic molecule. The ocular location where Ap4A actions have
not been fully elucidated is in the retina. Although some analogues show
interesting actions on pathological situations such as retinal detachment, little
is known about the real effect of this dinucleotide, this being one of the
challenges that require pursuing in the near future.
PMID- 28414591
TI - Violence Victimization, Social Support, and Papanicolaou Smear Outcomes: A
Longitudinal Study from Adolescence to Young Adulthood.
AB - BACKGROUND: African American youth are among those at greatest risk for
experiencing violence victimization. Notably, the mortality rate of cervical
cancer for African American women is also twice that of white women. To date, we
know of no literature using longitudinal data to examine how violence
victimization relates to Papanicolaou (Pap) smear results or cervical cancer in
this population. Our study examines how violence victimization during adolescence
(age 15 to 18) influences psychological distress, perceived social support, heavy
substance abuse, and sexual risk behaviors during emerging adulthood (age 20 to
23), and subsequent Pap smear outcomes during young adulthood (age 29 to 32).
METHOD: This study is based on 12 waves of data collected in a longitudinal study
of 360 African American women from mid-adolescence (ninth grade, mean age = 14.8
years) to young adulthood (mean age = 32.0 years). We used structural equation
modeling analysis to examine the hypothesized model. RESULT: Violence
victimization during adolescence had a direct effect on decreased social support,
increased psychological distress, and increased heavy cigarette use during
emerging adulthood. Better social support was also associated with fewer sexual
partners during emerging adulthood and lower odds of abnormal Pap smear results
during young adulthood. The effect of violence victimization on abnormal Pap
smear was mediated by social support. CONCLUSION: Our results show that violence
victimization during adolescence has long-term negative effects through multiple
pathways that persist into adulthood. Our findings also suggest that social
support may help to compensate against other risk factors. Interventions designed
to address the perceived support may help victims cope with their experience.
PMID- 28414593
TI - Letters to the Editor.
PMID- 28414594
TI - Pathology in Practice.
PMID- 28414595
TI - Advocating for your interests on Capitol Hill.
PMID- 28414596
TI - Anesthesia Case of the Month.
PMID- 28414597
TI - Bovine colostral cells-the often forgotten component of colostrum.
PMID- 28414599
TI - What Is Your Diagnosis?
PMID- 28414600
TI - Pathology in Practice.
PMID- 28414601
TI - Agreement between microscopic examination and bacterial culture of bile samples
for detection of bactibilia in dogs and cats with hepatobiliary disease.
AB - OBJECTIVE To evaluate the agreement between results of microscopic examination
and bacterial culture of bile samples from dogs and cats with hepatobiliary
disease for detection of bactibilia. DESIGN Cross-sectional study. ANIMALS 31
dogs and 21 cats with hepatobiliary disease for which subsequent microscopic
examination and bacterial culture of bile samples was performed from 2004 through
2014. PROCEDURES Electronic medical records of included dogs and cats were
reviewed to extract data regarding diagnosis, antimicrobials administered, and
results of microscopic examination and bacterial culture of bile samples.
Agreement between these 2 diagnostic tests was assessed by calculation of the
Cohen kappa value. RESULTS 17 (33%) dogs and cats had bactibilia identified by
microscopic examination of bile samples, and 11 (21%) had bactibilia identified
via bacterial culture. Agreement between these 2 tests was substantial
(percentage agreement [positive and negative results], 85%; kappa = 0.62; 95%
confidence interval, 0.38 to 0.89) and improved to almost perfect when calculated
for only animals that received no antimicrobials within 24 hours prior to sample
collection (percentage agreement, 94%; kappa = 0.84; 95% confidence interval,
0.61 to 1.00). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that
agreement between microscopic examination and bacterial culture of bile samples
for detection of bactibilia is optimized when dogs and cats are not receiving
antimicrobials at the time of sample collection. Concurrent bacterial culture and
microscopic examination of bile samples are recommended for all cats and dogs
evaluated for hepatobiliary disease.
PMID- 28414602
TI - What Is Your Neurologic Diagnosis?
PMID- 28414603
TI - Cardiovascular findings in ponies with equine metabolic syndrome.
AB - OBJECTIVE To determine whether hypertension, high sympathetic tone, resting and
exercising arrhythmias, and echocardiographic changes consistent with
hypertensive cardiomyopathy were associated with equine metabolic syndrome (EMS)
in ponies. DESIGN Prospective case-control study. ANIMALS 19 privately owned
ponies with a diagnosis of EMS (history of laminitis, body condition score >=
7/9, cresty neck score >= 3/5, and abnormal oral sugar test result; cases) and 20
healthy control ponies. PROCEDURES Heart rate (HR), noninvasively measured
arterial blood pressure (BP), markers of autonomic tone (splenic volume and HR
variability), 24-hour and exercising ECGs, and echocardiograms were compared
between cases and controls. RESULTS Compared with controls, cases had a higher
mean +/- SD HR (44.5 +/- 7.5 beats/min vs 38.6 +/- 6.8 beats/min) and median mean
left ventricular wall thickness (2.0 cm vs 1.8 cm). No differences were
identified between groups in BP, splenic volume, HR variability, and number of
premature complexes in ECGs. Mean wall thickness was correlated with BP (r =
0.54), high-frequency power (r = -0.71), and ratio of low-to high-frequency power
(phi = 0.66). Relative wall thickness was correlated with serum insulin
concentration (r = 0.71). CONCLUSIONS AND CLINICAL RELEVANCE Ponies with EMS had
myocardial hypertrophy that was correlated with insulin response to an oral sugar
test, sympathetic and parasympathetic tone, and BP. The heterogeneity and limited
sample size of this preliminary study should be considered when drawing
conclusions. Cardiovascular changes associated with this syndrome deserve further
attention.
PMID- 28414605
TI - Use of a novel surgical approach for treatment of complete bilateral membranous
choanal atresia in an alpaca cria.
AB - CASE DESCRIPTION A 4-hour-old 6.3-kg (13.9-lb) female alpaca cria was evaluated
because of severe respiratory distress and difficulty nursing since birth.
CLINICAL FINDINGS The cria had open-mouth breathing and cyanotic membranes, with
no airflow evident from either nostril. Supplemental oxygen was delivered, and
the patient was anesthetized and intubated orotracheally; a CT evaluation of the
head confirmed bilateral membranous obstruction of the nasal cavities, consistent
with complete bilateral choanal atresia. TREATMENT AND OUTCOME Choanal atresia
was treated with an endoscopically assisted balloon-dilation technique, and
temporary tracheostomy was performed. Stenosis recurred, requiring revision of
the repair and intranasal stent placement 3 days after the first surgery. The
tracheostomy tube was removed the next day. Complications during hospitalization
included mucoid obstruction of the tracheostomy tube, granulation tissue
development in the trachea near the tracheostomy site, mucoid stent obstruction,
aspiration pneumonia, and presumed partial failure of passive transfer of
immunity. The stents were removed 2 weeks after admission, and the cria was
discharged 3 days later. The owner was advised that the animal should not be
bred. At last follow-up 3 years later, the alpaca was doing well. CLINICAL
RELEVANCE Surgical treatment with a balloon-dilation technique and placement of
nasal stents with endoscopic guidance were curative in this neonatal alpaca with
bilateral membranous choanal atresia. Computed tomography was useful to determine
the nature of the atresia and aid surgical planning. Because a genetic component
is likely, owners should be advised to prevent affected animals from breeding.
PMID- 28414606
TI - Effects of topically applied heterologous serum on reepithelialization rate of
superficial chronic corneal epithelial defects in dogs.
AB - OBJECTIVE To assess the effects of topical application of undiluted heterologous
serum on time to corneal reepithelialization in dogs with superficial chronic
corneal epithelial defects (SCCEDs). DESIGN Multicenter, randomized, double
masked, controlled clinical trial. ANIMALS 41 client-owned dogs. PROCEDURES After
collection of baseline clinical and historical data, dogs were randomly assigned
to receive topically applied undiluted heterologous serum (n = 22) or isotonic
saline (0.9% NaCl) solution (19) along with tobramycin and atropine. Epithelial
debridement (at all visits) and grid keratotomy (at visits 2, 3, and 4) of SCCEDs
were performed. Ophthalmic examination including fluorescein application was
performed once weekly for 4 weeks or until corneal reepithelialization.
Clinicians and owners were masked to treatment group. RESULTS No differences in
baseline data were detected between treatment groups. No difficulties with
medication administration, noncompliance, or adverse reactions were noted. All
SCCEDs in both groups healed by 4 weeks after treatment began. Median time to
reepithelialization (2 weeks) was not significantly different between serum
treated and placebo-treated eyes. Irrespective of treatment group, median time to
reepithelialization was not significantly different for Boxers versus non-Boxer
breeds. Direct correlations were detected between time to reepithelialization and
vascularization score at study entry, vascularization score at time of
reepithelialization, and ulcer area at study entry in both groups. Time to
reepithelialization was not correlated with age, sex, or duration of signs in
either group. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of undiluted
heterologous serum was well tolerated by dogs with SCCEDs but, as an adjunct to
standard treatment, did not reduce time to corneal reepithelialization.
PMID- 28414607
TI - Cardiac arrest in an American Cocker Spaniel during a deep ear flush procedure.
AB - CASE DESCRIPTION A 14-year-old spayed female American Cocker Spaniel with
bilateral otitis media and no evidence of cardiovascular instability was
anesthetized to allow performance of a deep ear flush. CLINICAL FINDINGS
Otoscopic examination of the left ear revealed evidence of chronic inflammation;
the ear was flushed with sterile saline (0.9% NaCl) solution. Examination of the
right ear revealed more severe chronic inflammation than in the left ear,
including a ruptured tympanum (timing of rupture unknown). The right ear was
flushed with sterile saline solution, and several drops of otic medication were
instilled. During infusion of saline solution, the ECG revealed a rapid decrease
in heart rate until no more electrical activity was noted. Pulse also ceased to
be detectable via pulse oximetry and femoral artery palpation. TREATMENT AND
OUTCOME Isoflurane was discontinued immediately after recognition of cardiac
arrest. Shortly after, atropine (0.04 mg/kg [0.02 mg/lb]) and epinephrine (0.3
mg/kg [0.14 mg/lb]) were administered IV, chest compressions and ventilation were
performed for 2 to 3 minutes, and 3 boluses (each 5 mL/kg) of lactated Ringer
solution were administered IV. The dog was extubated 8 minutes after anesthesia
was discontinued, and its recovery was monitored for the next 5 hours. No further
incidents of cardiac arrest occurred after recovery from anesthesia. CLINICAL
RELEVANCE This case represented a rarely documented potential complication
associated with otic manipulation in a dog: cardiac arrest secondary to
stimulation of the auricular branch of the vagus nerve. Veterinarians should be
prepared for and warn clients of this possibility prior to otic flushing.
PMID- 28414609
TI - Association Between Androgen Receptor Splice Variants and Prostate Cancer
Resistance to Abiraterone and Enzalutamide.
PMID- 28414608
TI - Mechanobehavioral Scores in Women with and without TMJ Disc Displacement.
AB - Cartilage fatigue may be a factor in the precocious development of degenerative
changes in the temporomandibular joint (TMJ). This cross-sectional study
estimated potential for cartilage fatigue via TMJ energy densities (ED) and jaw
muscle duty factors (DF), which were combined to calculate mechanobehavioral
scores (MBS) in women with (+) and without (-) bilateral TMJ disc displacement
(DD). All subjects gave informed consent to participate and were examined using
Diagnostic Criteria (DC) for Temporomandibular Disorders (TMD) and magnetic
resonance (MR) and computed tomography (CT) images. Forty-seven subjects were
categorized into +DD ( n = 29) and -DD ( n = 18) groups. Dynamic stereometry (MR
images combined with jaw-tracking data) characterized individual-specific data of
TMJ stress-field mechanics to determine ED (ED = W/ Q mJ/mm3, where W = work
done, Q = volume of cartilage) during 10 symmetrical jaw-closing cycles with a 20
N mandibular right canine load. Subjects were trained to record masseter and
temporalis electromyography over 3 days and 3 nights. Root mean square
electromyography/bite-force calibrations determined subject-specific masseter and
temporalis muscle activities per 20-N bite-force (T20 N, uV), which defined
thresholds. Muscle DF (DF = % duration of muscle activity/total recording time)
were determined for a range of thresholds, and MBS (ED2 * DF) were calculated.
Intergroup differences in ED, DF, and MBS were assessed via analyses of variance
with Bonferroni and Tukey honest significant difference post hoc tests. Average
ED for contralateral TMJs was significantly larger ( P = 0.012) by 1.4-fold in
+DD compared to -DD subjects. Average DF were significantly larger (all P < 0.01)
for +DD compared to -DD subjects by 1.7-, 2.5-, and 1.9-fold for day, night, and
overall, respectively. Daytime MBS were significantly larger (all P < 0.04) by up
to 8.5-fold in +DD compared to -DD subjects. Significantly larger ED, DF, and MBS
were shown in women with compared to women without bilateral TMJ DD.
PMID- 28414611
TI - Population Genetic Structure of Venturia effusa, Cause of Pecan Scab, in the
Southeastern United States.
AB - Venturia effusa is the most important pathogen of pecan in the southeastern
United States. Little information exists on the population biology and genetic
diversity of the pathogen. A hierarchical sampling of 784 isolates from 63 trees
in 11 pecan orchards in the southeastern United States were screened against a
set of 30 previously characterized microsatellite markers. Populations were
collected from Georgia (n = 2), Florida (n = 1), Alabama (n = 2), Mississippi (n
= 1), Louisiana (n = 1), Illinois (n = 1), Oklahoma (n = 1), Texas (n = 1), and
Kansas (n = 1). Clonality was low in all orchard populations (<=10.1% of
isolates), and there were consistently high levels of genotypic diversity
(Shannon-Weiner's index = 3.49 to 4.59) and gene diversity (Nei's measure = 0.513
to 0.713). Analysis of molecular variance showed that, although 81% of genetic
diversity occurred at the scale of the individual tree, 16% occurred between
orchards and only 3% between trees within orchards. All populations could be
differentiated from each other (P = 0.01), and various cluster analyses indicated
that some populations were more closely related compared with other pairs of
populations. This is indicative of some limited population differentiation in V.
effusa in the southeastern United States. Bayesian and nearest-neighbor methods
suggested eight clusters, with orchards from Georgia and Florida being grouped
together. A minimum spanning tree of all 784 isolates also indicated some isolate
identification with source population. Linkage disequilibrium was detected in all
but one population (Kansas), although 8 of the 11 populations had <20% of loci at
disequilibrium. A Mantel test demonstrated a relationship between physical and
genetic distance between populations (Z = 11.9, r = 0.559, P = 0.001). None of
the populations were at mutation-drift equilibrium. All but 3 of the 11
populations had a deficiency of gene diversity compared with that expected at
mutation-drift equilibrium (indicating population expansion); the remaining
populations had an excess of gene diversity compared with that expected at
mutation-drift equilibrium (indicating a recent bottleneck). These observations
are consistent with the known history of pecan and pecan scab, which is that V.
effusa became an issue on cultivated pecan in the last approximately 120 years
(recent population expansion). Recently reported mating type genes and the sexual
stage of this fungus may help explain the observed population characteristics,
which bear a strong resemblance to those of other well-characterized sexually
reproducing ascomycete pathogens.
PMID- 28414610
TI - Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An
Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en
Cancerologie Digestive Database.
AB - Purpose Factors contributing to early mortality after initiation of treatment of
metastatic colorectal cancer are poorly understood. Materials and Methods Data
from 22,654 patients enrolled in 28 randomized phase III trials contained in the
ARCAD (Aide et Recherche en Cancerologie Digestive) database were pooled.
Multivariable logistic regression models for 30-, 60-, and 90-day mortality were
constructed, including clinically and statistically significant patient and
disease factors and interaction terms. A calculator (nomogram) for 90-day
mortality was developed and validated internally using bootstrapping methods and
externally using a 10% random holdout sample from each trial. The impact of early
progression on the likelihood of survival to 90 days was examined with time
dependent Cox proportional hazards models. Results Mortality rates were 1.4% at
30 days, 3.4% at 60 days, and 5.5% at 90 days. Among baseline factors, advanced
age, lower body mass index, poorer performance status, increased number of
metastatic sites, BRAF mutant status, and several laboratory parameters were
associated with increased likelihood of early mortality. A multivariable model
for 90-day mortality showed strong internal discrimination (C-index, 0.77) and
good calibration across risk groups as well as accurate predictions in the
external validation set, both overall and within patient subgroups. Conclusion A
validated clinical nomogram has been developed to quantify the risk of early
death for individual patients during initial treatment of metastatic colorectal
cancer. This tool may be used for patient eligibility assessment or risk
stratification in future clinical trials and to identify patients requiring more
or less aggressive therapy and additional supportive measures during and after
treatment.
PMID- 28414612
TI - Multimodal Imaging in Masquerade Syndromes.
AB - Masquerade syndromes present to uveitis clinics due to the appearance of
inflammatory signs and chronic symptoms that are not responsive to conventional
treatment. They are frequently misdiagnosed and treated as refractory
inflammatory conditions, which delays appropriate diagnosis and management. This
review of literature focuses on the commonly encountered masquerade syndromes and
discusses the role of multimodal imaging in addressing these complex clinical
presentations. We review the conventional imaging techniques for these patients
and discuss emerging technological advances that may help in establishing a
diagnosis. We present cases highlighting the utility of multimodal imaging in
identifying the etiology.
PMID- 28414613
TI - Sympathetic Ophthalmia.
PMID- 28414614
TI - Intracorporeal Circular Stapled Esophagojejunostomy Using Conventional Purse
String Suture Instrument After Laparoscopic Total Gastrectomy.
AB - BACKGROUND: An optimal alimentary tract reconstruction technique after
laparoscopic total gastrectomy (LTG) remains controversial. The authors developed
a new simple technique for intracorporeal esophagojejunal anastomosis that
employs a conventional purse-string suture instrument (PSI) and circular stapler.
METHODS: From May 2014 to April 2016, 41 consecutive patients with gastric cancer
underwent LTG in the author's institution. Intracorporeal esophagojejunal
anastomosis using the following method was attempted for all patients. After
total gastrectomy was completed laparoscopically, a small vertical incision
(about 40 mm) was created at the left midclavicular line and retracted by a wound
retractor. An anvil of a 25 mm circular stapler was introduced into the abdominal
cavity. Then a previously prepared surgical glove, which was cut open at the
thumb and the little finger through which the two hand shafts of the PSI were
passed separately and sealed by ties, was attached to the wound retractor to
maintain airtightness, and the PSI was introduced into the abdominal cavity. The
following procedure was similar to conventional open surgery except that it was
performed under laparoscopic vision. RESULTS: Intracorporeal esophagojejunal
anastomosis was performed successfully for all 41 patients. No case required
extension of the initial incision for difficulties during anastomosis. The mean
operation time was 245 minutes, and the mean time for the purse-string suture and
anvil placement was 15 minutes. Tumor-free margins were achieved in all 41
patients. There were no anastomosis-related complications or other major surgical
complications. CONCLUSIONS: With the described method, intracorporeal
esophagojejunal anastomosis can be performed easily and safely.
PMID- 28414615
TI - Virulence profile: Juliana Campos Junqueira.
PMID- 28414617
TI - Theorizing the Impact of Targeted Narratives: Model Admiration and Narrative
Memorability.
AB - Communication campaigns often include components that have been designed for a
specific population, a strategy referred to as targeting. Targeted narratives are
story-based components of a campaign that feature a character or situation
relevant to the intended audience. Though commonplace, few studies have
explicated the underlying mechanisms by which targeted narratives exert
influence. In a message evaluation study, 316 women aged 40-75 (Mage = 51.19, SD
= 8.11) were exposed to one of two targeted narratives and asked to complete
measures of model admiration, narrative memorability, and intentions to receive a
mammography. Targeting was based upon affiliation with the Mormon church. The
results revealed that the relationship between the targeted narratives and
screening intentions was especially strong for women from the target population
who admired the depicted models and found the stories memorable.
PMID- 28414616
TI - Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue
Engineered Cartilage Constructs Across Testing Platforms.
AB - Cartilage tissue engineering is emerging as a promising treatment for
osteoarthritis, and the field has progressed toward utilizing large animal models
for proof of concept and preclinical studies. Mechanical testing of the
regenerative tissue is an essential outcome for functional evaluation. However,
testing modalities and constitutive frameworks used to evaluate in vitro grown
samples differ substantially from those used to evaluate in vivo derived samples.
To address this, we developed finite element (FE) models (using FEBio) of
unconfined compression and indentation testing, modalities commonly used for such
samples. We determined the model sensitivity to tissue radius and subchondral
bone modulus, as well as its ability to estimate material parameters using the
built-in parameter optimization tool in FEBio. We then sequentially tested
agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation
platform, followed by unconfined compression. Similarly, we evaluated the ability
of the model to generate material parameters for living constructs by evaluating
engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 * 107
cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a
chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested
sequentially in indentation and unconfined compression. The model successfully
completed parameter optimization routines for each testing modality for both
acellular and cell-based constructs. Traditional outcome measures and the FE
derived outcomes showed significant changes in material properties during the
maturation of engineered cartilage tissue, capturing dynamic changes in
functional tissue mechanics. These outcomes were significantly correlated with
one another, establishing this FE modeling approach as a singular method for the
evaluation of functional engineered and native tissue regeneration, both in vitro
and in vivo.
PMID- 28414618
TI - Understanding Spanish-Language Response in a National Health Communication
Survey: Implications for Health Communication Research.
AB - : Spanish-speaking Latinos account for 13% of the U.S. population yet are
chronically under-represented in national surveys; additionally, the response
quality suffers from low literacy rates and translation challenges. These are the
same issues that health communicators face when understanding how best to
communicate important health information to Latinos. The Health Information
National Trends Survey (HINTS) offers a unique opportunity to understand the
health communication landscape and information needs of the U.S. POPULATION: We
describe the challenges in recruiting Spanish-speaking HINTS respondents and
strategies used to improve rates and quality of responses among Spanish-speaking
Latinos. Cognitive interviewing techniques helped to better understand how
Spanish-speaking Latinos were interpreting the survey questions, and the extent
to which these interpretations matched English-speaking respondents'
interpretations. Some Spanish-speaking respondents had difficulty with the
questions because of a lack of access to health care. Additionally, Spanish
speaking respondents had a particularly hard time answering questions that were
presented in a grid format. We describe the cognitive interview process, and
consider the impact of format changes on Spanish-speaking people's responses and
response quality. We discuss challenges that remain in understanding health
information needs of non-English-speakers.
PMID- 28414619
TI - How the nerves reached the muscle: Bernard Katz, Stephen W. Kuffler, and John C.
Eccles-Certain implications of exile for the development of twentieth-century
neurophysiology.
AB - This article explores the work by Bernard Katz (1911-2003), Stephen W. Kuffler
(1913-1980), and John C. Eccles (1903-1997) on the nerve-muscle junction as a
milestone in twentieth-century neurophysiology with wider scientific
implications. The historical question is approached from two perspectives: (a) an
investigation of twentieth-century solutions to a longer physiological dispute
and (b) an examination of a new kind of laboratory and academic cooperation. From
this vantage point, the work pursued in Sydney by Sir John Carew Eccles' team on
the neuromuscular junction is particularly valuable, since it contributed a
central functional element to modern physiological understanding regarding the
function and structure of the human and animal nervous system. The reflex model
of neuromuscular action had already been advanced by neuroanatomists such as
Georg Prochaska (1749-1820) in Bohemia since the eighteenth century. It became a
major component of neurophysiological theories during the nineteenth century,
based on the law associated with the names of Francois Magendie (1783-1855) in
France and Charles Bell (1774-1842) in Britain regarding the functional
differences of the sensory and motor spinal nerves. Yet, it was not until the
beginning of the twentieth century that both the histological and the
neurophysiological understanding of the nerve-muscle connection became entirely
understood and the chemical versus electrical transmission further elicited as
the mechanisms of inhibition. John C. Eccles, Bernard Katz, and Stephen W.
Kuffler helped to provide some of the missing links for modern neurophysiology.
The current article explores several of their scientific contributions and
investigates how the context of forced migration contributed to these
interactions in contingently new ways.
PMID- 28414621
TI - The American Association of Occupational Health Nurses: Seventy-Five Years of
Education, Practice, and Research.
AB - For the past 75 years, the American Association of Industrial Nurses, and later
the American Association of Occupational Health Nurses, has advocated for
occupational and environmental health nurses by supporting quality undergraduate
and graduate education in the specialty and certification through the American
Board of Occupational Health Nurses, Inc., and providing funding for and
dissemination of occupational health nursing research as well as by developing
occupational health nursing practice standards, competencies, and code of ethics.
PMID- 28414622
TI - Clostridium difficile Infection.
AB - Preventing Clostridium difficile, the most common cause of health care-associated
infections in hospitals and infectious disease death in the United States, is a
national priority. Increased rates of infection among low-risk individuals in the
community call for community-based prevention efforts to halt the increasing
spread of this highly contagious opportunistic infection.
PMID- 28414623
TI - Licensed Practical/Vocational Nurses: A Place on the Team.
PMID- 28414624
TI - History, Passion, and Performance.
AB - History, Passion, and Performance was chosen as the theme for the 75th
anniversary of the American Association of Occupational Health Nurses (AAOHN)
kickoff. The American Association of Occupational Health Nurses has a long
history created by passionate, dedicated members. This article highlights
historical foundations of the Association, describes the occupational health
nurse's passion to drive quality care for workers and discusses future
professional and organizational challenges.
PMID- 28414625
TI - Advancing Well-Being Through Total Worker Health(r).
AB - Total Worker Health(r) (TWH) is a paradigm-shifting approach to safety, health,
and well-being in the workplace. It is defined as policies, programs, and
practices that integrate protection from work-related safety and health hazards
with promotion of injury and illness prevention efforts to advance worker well
being. The most current TWH concepts are presented, including a description of
issues relevant to TWH and introduction of a hierarchy of controls applied to
TWH. Total Worker Health advocates for a foundation of safety and health through
which work can contribute to higher levels of well-being.
PMID- 28414626
TI - The Future of Occupational Health Nursing in a Changing Health Care System.
AB - Repealing the Affordable Care Act (ACA) has significant implications for the
future of occupational health nursing practice. As changes are proposed and
implemented, occupational health nurses must continue to prioritize preventive
care, chronic disease management, healthy communities, environmental health, and
sustainability. In particular, immigrant workers are a vulnerable population
needing attention by occupational health nurses.
PMID- 28414627
TI - The Dangers of Electrosurgical Smoke to Operating Room Personnel: A Review.
AB - A 2007 study in the United Kingdom showed that three of 98 surgeons surveyed
admitted using dedicated smoke extractors; 72% of respondents believed inadequate
precautions were in place to protect staff from the potential dangers of
electrosurgical smoke. Surgical smoke contains harmful chemicals (e.g., hydrogen
cyanide, acetylene, and butadiene) that can circumvent standard masks used in the
operating room (OR). In addition, bacteria and viruses can be transmitted through
this smoke. The topic of electrosurgical smoke is important to occupational
health nurses not only because of their responsibility to protect workers, but
also because they, like other health care providers, may be exposed to smoke
routinely. The authors of this review recommend the regular use of smoke
evacuation in ORs and avoidance of electrosurgery whenever possible to protect OR
personnel from the potential long-term harmful effects of electrosurgical smoke.
PMID- 28414628
TI - Fried Green Tomatoes and The Color Purple: A case study in lesbian friendship and
cultural controversy.
AB - Published in the 1980s, Fannie Flagg's Fried Green Tomatoes at the Whistle Stop
Cafe and Alice Walker's The Color Purple are lesbian coming-of-age narratives
that share a great deal in common in terms of their thematic content, publication
histories, and cultural afterlives. In both novels, female friendships are shaped
by patriarchal violence and develop in the context of the rural, segregated,
early twentieth-century U.S. South. But the two novels also diverge in
significant ways, as differences in race, gender, class, and sexuality shape
their protagonists' experiences of love and friendship. As filmmakers Steven
Spielberg and Jon Avnet adapted these novels for the screen, they made decisions
about how to portray the texts' representations of homoerotic friendship and same
sex love. Both films generated significant cultural controversy as a result,
particularly as some viewers claimed that the films elided the novels'
representations of lesbian sexuality. Building upon recent scholarship in
critical race theory, queer theory, and friendship studies, I argue that Walker's
and Flagg's representations of queer friendship, a term that I describe in more
detail throughout the essay, subvert dominant classifications of romantic,
familial, and platonic love. By comparatively analyzing the American public's
reception of the two film adaptations in conjunction with close readings of
scenes from the novels and films, I reveal how representations of queer
friendship not only catalyze cultural controversy, but also serve as a vehicle of
social criticism.
PMID- 28414629
TI - Effects of chemotherapy on the health-related quality of life of Japanese lower
rectal cancer patients after sphincter-saving surgery.
AB - We examined the effects of adjuvant chemotherapy on the health-related quality of
life (HRQOL) of lower rectal cancer patients receiving sphincter-saving surgery
(SSS). In all, 109 patients completed a questionnaire before surgery and 1, 6,
and 12 months afterwards. In the chemotherapy group, physical and social
functioning scores were significantly lower 12 months after surgery compared with
the nonchemotherapy group. These effects of adjuvant chemotherapy suggest that a
different clinical approach might more effectively improve physical and social
functioning in lower-rectal cancer patients undergoing chemotherapy. Healthcare
providers should be alert for adverse events in patients with lower-rectal cancer
and promptly address such conditions.
PMID- 28414630
TI - Infection Courts in Watermelon Plants Leading to Seed Infestation by Fusarium
oxysporum f. sp. niveum.
AB - Fusarium wilt incited by Fusarium oxysporum f. sp. niveum is a seed-transmitted
disease that causes significant yield loss in watermelon production. The pathogen
may infect watermelon seeds latently, which can be an important inoculum source
and contribute to severe disease outbreak. However, information regarding
infection courts of F. oxysporum f. sp. niveum leading to infestation of
watermelon seeds is limited. To determine how seeds in watermelon fruit can be
infested by F. oxysporum f. sp. niveum during the watermelon growing season,
greenhouse and field experiments were conducted in 2014 and 2015 where watermelon
flowers and immature fruit were inoculated with F. oxysporum f. sp. niveum. Seeds
were extracted from mature watermelon fruit, and infestation of watermelon seeds
was determined by isolation of F. oxysporum f. sp. niveum and further confirmed
by real-time polymerase chain reaction (PCR) analysis. Inoculation of the
pericarp of immature fruit resulted in 17.8 to 54.4% of infested seeds under
field conditions and 0.6 to 12.8% of infested seeds under greenhouse conditions
when seeds were not surface disinfested prior to isolation. Seed infestation was
also detected in 0 to 4.5% of the seeds when seeds were surface disinfested prior
to isolation. Inoculation of pistil resulted in 0 to 7.2% and 0 to 18.3% of
infested seeds under greenhouse and field conditions when seeds were surface
disinfested or not disinfested before isolation, respectively. Inoculation of
peduncle resulted in 0.6 to 6.1% and 0 to 10.0% of infested seeds in the
greenhouse and field experiments when seeds were surface disinfested or not
disinfested before isolation, respectively. Seed infestation was also detected in
all the experiments using real-time PCR assay when pericarp or pistil was
inoculated, and in three of four experiments when peduncle was inoculated,
regardless of whether seeds were surface disinfested or not disinfested. Pericarp
and peduncle of immature watermelon fruit and pistil of watermelon flowers could
be potential infection courts for F. oxysporum f. sp. niveum leading to
infestation of seeds in asymptomatic watermelon fruit.
PMID- 28414631
TI - Rathayibacter toxicus, Other Rathayibacter Species Inducing Bacterial Head Blight
of Grasses, and the Potential for Livestock Poisonings.
AB - Rathayibacter toxicus, a Select Agent in the United States, is one of six
recognized species in the genus Rathayibacter and the best known due to its
association with annual ryegrass toxicity, which occurs only in parts of
Australia. The Rathayibacter species are unusual among phytopathogenic bacteria
in that they are transmitted by anguinid seed gall nematodes and produce
extracellular polysaccharides in infected plants resulting in bacteriosis
diseases with common names such as yellow slime and bacterial head blight. R.
toxicus is distinguished from the other species by producing corynetoxins in
infected plants; toxin production is associated with infection by a
bacteriophage. These toxins cause grazing animals feeding on infected plants to
develop convulsions and abnormal gate, which is referred to as "staggers," and
often results in death of affected animals. R. toxicus is the only recognized
Rathayibacter species to produce toxin, although reports of livestock deaths in
the United States suggest a closely related toxigenic species may be present. A
closely related but undescribed species, Rathayibacter sp. EV, originally
isolated from Ehrharta villosa var. villosa in South Africa, is suspected of
producing toxin. Many of the diseases caused by Rathayibacter species occur in
arid areas and the extracellular polysaccharide they produce is believed to aid
in their survival between crops. For example, R. "agropyri" was isolated from
infected plant material after being stored for 50 years in a herbarium.
Similarly, the anguinid vectors associated with these bacteria form seed galls in
infected plants and are capable of surviving for very long periods of time under
dry conditions. The addition of R. toxicus to the list of Select Agents has
raised concern over its potential introduction and a realization that current
diagnostic methods are inadequate to distinguish among Rathayibacter species. In
addition, little is known about the Rathayibacter species and their seed gall
nematode vectors present in the United States.
PMID- 28414632
TI - Analysis of the Spatial Pattern of Strawberry Angular Leaf Spot in California
Nursery Production.
AB - In California, angular leaf spot (ALS) is a common disease in strawberry nursery
production, and a major concern for nurseries wishing to export plants. As the
spatial pattern of a disease can offer insight into pathogen source, mode of
dissemination, and how current crop management practices affect epidemic
development, an understanding of the spatial pattern of ALS would allow nursery
growers to make informed decisions regarding disease management. Ninety-seven
field assessments of disease incidence were performed at different nursery
locations in 2014 and 2015 to quantify ALS spatial pattern under commercial
conditions. Both point-pattern and geostatistical statistical procedures were
used to analyze the data. The spatial pattern of ALS was characterized by a high
degree of heterogeneity, as indicated by high median values of the beta-binomial
distribution's theta parameter (0.643), and the index of dispersion, D (4.218).
The binary power law provided a robust description of the data with estimated
slope and intercept parameters significantly greater than 1 and 0, respectively
(P < 0.001). Spatial analysis by distance indices (SADIE) detected significant
nonrandom spatial arrangements for 64% of the data sets. Analysis of directional
disease spread showed a strong spatial association between sampling units along
the same planting row. This suggests that recurrent crop operations during the
growing season play a significant role in ALS spread and should be taken into
account to improve disease control.
PMID- 28414633
TI - Genome-Wide Analysis Provides Evidence on the Genetic Relatedness of the Emergent
Xylella fastidiosa Genotype in Italy to Isolates from Central America.
AB - Xylella fastidiosa is a plant-pathogenic bacterium recently introduced in Europe
that is causing decline in olive trees in the South of Italy. Genetic studies
have consistently shown that the bacterial genotype recovered from infected olive
trees belongs to the sequence type ST53 within subspecies pauca. This genotype,
ST53, has also been reported to occur in Costa Rica. The ancestry of ST53 was
recently clarified, showing it contains alleles that are monophyletic with those
of subsp. pauca in South America. To more robustly determine the phylogenetic
placement of ST53 within X. fastidiosa, we performed a comparative analysis based
on single nucleotide polymorphisms (SNPs) and the study of the pan-genome of the
27 currently public available whole genome sequences of X. fastidiosa. The
resulting maximum-parsimony and maximum likelihood trees constructed using the
SNPs and the pan-genome analysis are consistent with previously described X.
fastidiosa taxonomy, distinguishing the subsp. fastidiosa, multiplex, pauca,
sandyi, and morus. Within the subsp. pauca, the Italian and three Costa Rican
isolates, all belonging to ST53, formed a compact phylotype in a clade divergent
from the South American pauca isolates, also distinct from the recently described
coffee isolate CFBP8072 imported into Europe from Ecuador. These findings were
also supported by the gene characterization of a conjugative plasmid shared by
all the four ST53 isolates. Furthermore, isolates of the ST53 clade possess an
exclusive locus encoding a putative ATP-binding protein belonging to the family
of histidine kinase-like ATPase gene, which is not present in isolates from the
subspecies multiplex, sandyi, and pauca, but was detected in ST21 isolates of the
subspecies fastidiosa from Costa Rica. The clustering and distinctiveness of the
ST53 isolates supports the hypothesis of their common origin, and the limited
genetic diversity among these isolates suggests this is an emerging clade within
subsp. pauca.
PMID- 28414635
TI - Ann Veronica Janssens: yellowbluepink.
PMID- 28414634
TI - Detection of the Canine Parvovirus 2c Subtype in Australian Dogs.
AB - Canine parvovirus (CPV-2) is an important cause of hemorrhagic enteritis in dogs.
In Australia the disease has been associated with CPV-2a and CPV-2b variants. A
third more recently emerged variant overseas, CPV-2c, has not been detected in
surveys of the Australian dog population. In this study, we report three cases of
canine parvoviral enteritis associated with CPV-2c infection; case 1 occurred in
an 8-week-old puppy that died following acute hemorrhagic enteritis. Cases 2 and
3 were an 11-month-old female entire Saint Bernard and a 9-month-old male entire
Siberian husky, respectively, both which had completed vaccination schedules and
presented with vomiting or mild diarrhea only. Full genomic sequencing of
parvoviral DNA from cases 1, 2, and 3 revealed greater than 99% homology to known
CPV-2c variants and predicted protein sequences from the VP2 region of viral DNA
from all three cases identified; glutamic acid residues at the 426 amino acid
residue, characteristic of the CPV-2c variant. Veterinary professionals should be
aware that CPV-2c is now present in Australia, detected in a puppy and vaccinated
young adult dogs in this study. Further characterization of CPV-2c-associated
disease and its prevalence in Australian dogs requires additional research.
PMID- 28414636
TI - Connectome: dancing through neuronal circuits.
PMID- 28414637
TI - Lessons learned from Christmas lectures.
PMID- 28414638
TI - An orange and Alzheimer's disease?
PMID- 28414639
TI - Memory, distraction, and nostalgia.
PMID- 28414640
TI - Richard Morris' Christmas lecture double-bill.
PMID- 28414641
TI - Vascular disease and neurodegeneration: advancing together.
PMID- 28414642
TI - Disease progression in LRRK2 parkinsonism.
PMID- 28414643
TI - Optimisation of stroke research.
PMID- 28414644
TI - Corrections.
PMID- 28414645
TI - Diagnosis and classification of optic neuropathies.
PMID- 28414646
TI - Membrane damage is at the core of Alzheimer's disease.
PMID- 28414647
TI - Diagnosis and classification of optic neuropathies - Authors' reply.
PMID- 28414648
TI - Remi W Bouchard, a pioneer in behavioural neurology.
PMID- 28414649
TI - Gaining ground against cerebral malaria.
PMID- 28414650
TI - Edor Kabashi.
PMID- 28414651
TI - Historical landmarks in dementia with Lewy bodies.
PMID- 28414652
TI - No past, no future: studies in the art and science of memory.
PMID- 28414653
TI - Increasing value and reducing waste in stroke research.
AB - Stroke is a major burden to patients and society, and resources spent on stroke
research must be used efficiently and produce good value in terms of improvements
in human health. However, many instances of poor value from stroke research
funding have resulted from the way in which stroke research topics have been
chosen and how studies have been designed, conducted, analysed, regulated,
managed, disseminated, or reported. A cooperative effort of European stroke
researchers aimed to identify sources of inefficiency and waste, recommend
approaches to increase value, and highlight examples of best practice in stroke
research. Evidence suggests that progress has been made, but there is room for
much improvement; researchers, funders, regulators, and other stakeholders in
stroke research might consider these recommendations when planning new research.
PMID- 28414654
TI - Left ventricular function determines the survival benefit for women over men
after transcatheter aortic valve implantation (TAVI).
AB - AIMS: There is evidence for a lower mortality in female patients after
transcatheter aortic valve implantation (TAVI), but the underlying reasons for
the gender-specific differences in prognosis are not well understood. In
particular, the role of left ventricular dysfunction is unclear. In this study,
we addressed the question of whether differences in left ventricular ejection
fraction (LVEF) could account for the gender benefit for female TAVI patients.
METHODS AND RESULTS: From January 2011 to December 2013, a total of 15,616
patients treated with TAVI were prospectively enrolled in the German Aortic Valve
Registry (GARY). For the present analysis, female TAVI patients (N=8,456) were
compared with male TAVI patients (N=7,160) with a particular focus on LVEF.
Mortality at one year was 18.1% in women and 22.6% in men (p<0.001). Multivariate
analysis also revealed that female gender was associated with a lower one-year
mortality (adjusted hazard ratio [HR] 0.88 [0.81-0.95]). There was no difference
in gender-specific mortality in patients with baseline LVEF >50% (women: 16.4%;
men 17.6%, p=0.268), but in patients with LVEF 30%-50% (21.0% versus 25.7%,
p<0.001) and <30% (26.2% versus 37.6%, p<0.001) one-year mortality was
significantly lower in women than in men. CONCLUSIONS: The survival benefit for
women over men after TAVI was only observed in patients with a preprocedural LVEF
<=50%.
PMID- 28414655
TI - Effect of early percutaneous coronary intervention on one-year risk of pneumonia
and pneumonia-related adverse outcomes in patients with acute myocardial
infarction.
AB - AIMS: The aim of this study was to investigate the association between early
percutaneous coronary intervention (PCI) and pneumonia risk in patients with
acute myocardial infarction (AMI) by using Taiwan's National Health Insurance
Research Database (NHIRD). METHODS AND RESULTS: In total, 4,732 patients with non
ST-elevation myocardial infarction (NSTEMI) and 5,465 with ST-elevation
myocardial infarction (STEMI) who had received PCI during AMI hospitalisation
(early PCI) were evaluated. Patients who did not receive PCI during AMI
hospitalisation (deferred PCI) were matched through propensity score matching.
The incidence rates (per 100 person-months) of pneumonia hospitalisation,
pneumonia-related respiratory failure, and pneumonia-related death associated
with early PCI in patients with NSTEMI were 0.36 (95% confidence interval [CI]:
0.32-0.42), 0.12 (95% CI: 0.10-0.16), and 0.08 (95% CI: 0.06-0.11), respectively.
In patients with STEMI, the incidence rates (per 100 person-months) of the
aforementioned adverse events were 0.16 (95% CI: 0.13-0.20), 0.04 (95% CI: 0.03
0.06), and 0.02 (95% CI: 0.01-0.04), respectively. After adjustment for patients'
clinical variables, early PCI was associated with reduced risks of pneumonia
hospitalisation (adjusted hazard ratio [aHR] 0.54, 95% CI: 0.43-0.68, p<0.001),
pneumonia-related respiratory failure (aHR 0.54, 95% CI: 0.35-0.84, p=0.006), and
pneumonia-related death (aHR 0.29, 95% CI: 0.17-0.52, p<0.001) in patients with
NSTEMI. In patients with STEMI, early PCI was beneficial for pneumonia
hospitalisation (aHR 0.62, 95% CI: 0.45- 0.86, p=0.004). CONCLUSIONS: Early PCI
might reduce the risk of pneumonia hospitalisation in patients with AMI.
PMID- 28414656
TI - Prevalence and outcomes of coronary artery perforation during percutaneous
coronary intervention.
AB - AIMS: We aimed to examine the prevalence, clinical outcomes and procedural
characteristics of percutaneous coronary intervention (PCI) complicated by
coronary artery perforation (CAP) in a contemporary patient population. METHODS
AND RESULTS: Procedural records of 39,115 patients undergoing PCI between 2005
and 2016 were reviewed. CAP affected 149 cases (0.37%). The prevalence of CAP
increased from 0.31% in 2005 to 0.45% in 2016 (p=0.03), reflecting an increase in
more complex PCI (from 14% in 2005 to 21% in 2016; p<0.0001). CAP was associated
with increased all-cause mortality (23.1% vs. 9.4% in those without perforation;
p=0.0054) and was an independent predictor of mortality (HR 2.55; 95% CI: 1.34
4.78). In-patient mortality was 4% (6/149). In 43 of 149 (28.9%) cases, a
significant pericardial effusion ensued and mortality rates were higher in this
subgroup. Thirty-one patients had covered stents (CS) inserted and five did not
survive to discharge. Of the 26 patients with a CS who survived to hospital
discharge, six (23.1%) had definite stent thrombosis, and two (7.7%) had
possible/probable stent thrombosis. CONCLUSIONS: CAP remains uncommon but the
prevalence is increasing. CAP is associated with significant short- and long-term
mortality, particularly when there is haemodynamic compromise necessitating
pericardiocentesis. Covered stents are a valuable tool but they are associated
with a high risk of stent thrombosis.
PMID- 28414657
TI - Death by Propofol.
AB - Since its introduction in 1986, propofol ( two, 6-diisopropylphenol) , an
intravenous sedative-hypnotic agent, has been utilized for the induction and
maintenance of general anesthesia and conscious sedation in over 80 percent of
cases; largely replacing thiopental ( sodium pentothal) over a decade ago.
Unrestricted as a controlled substance, propofol's abuse potential emerged
quickly and was highlighted by the death of pop singer, Michael Jackson, in 2009.
In order to assess the epidemiological features of fatal propofol abuse, a
descriptive analysis of the scientific literature was conducted using Internet
search engines. Well-documented cases of fatal propofol abuse were stratified as
unintentional or accidental deaths and as intentional deaths by suicides or
homicides. Continuous variables were compared for differences by unpaired, two
tailed t-tests with statistical significance indicated by p-values less than
0.05. Of 21 fatal cases of propofol abuse, 18 (86 percent ) occurred in
healthcare workers, mostly anesthesiologists and nurse anesthetists (n=14, 67
percent ). One case occurred in a layman who purchased propofol on the Internet.
Seventeen deaths (81 percent ) were accidental; two were suicides (9.5 percent )
and two were homicides (9.5 percent ). Blood levels in intentional death cases
were significantly greater than in accidental death cases (p less than 0.0001)
all of which reflected initial therapeutic induction-level doses in the ranges of
2.0-2.5 mg/kg. Though lacking in analgesic effects, the abuse of propofol by
young healthcare professionals, particularly operating room workers, has been
significant; and likely underreported. Propofol is a dangerous drug with an
evident abuse potential which often results in fatalities.
PMID- 28414658
TI - Septic Cerebral Venosinus Thrombosis Secondary to an Odontogenic Infection.
AB - BACKGROUND: Cerebral venosinus thrombosis (CVT); is an uncommon, potentially
fatal disease that is more common in young adults and children. Thrombophilia,
elevated estrogenic states, and infections are the most common risk factors in
patients who develop CVT. CASE: A 69-year-old man with a right-sided odontogenic
infection presented with fever, headache, opthalmoplegia, and periorbital
swelling. Imaging revealed evidence of meningitis and thrombosis of bilateral
ophthalmic veins, the cavernous sinus, right internal jugular vein, and sigmoid
sinus. The patient was treated with empiric antibiotic therapy and unfractionated
heparin. He recovered with only mild impairment in right eye abduction.
DISCUSSION: Early diagnosis and prompt treatment of CVT is vital in reducing the
associated morbidity and mortality. Unfractionated or low molecular weight
heparin may be safely used in CVT patients. Thrombolytic therapy is an option in
clinically severe cases. Treatment also includes addressing the underlying cause
and management of early complications.
PMID- 28414659
TI - Knowledge of HPV-Related Oropharyngeal Cancer and Use of Human Papillomavirus
Vaccines by Pediatricians in Louisiana.
AB - OBJECTIVES: To determine the level of knowledge of HPV related oropharyngeal
cancer and practice patterns of HPV vaccine use by pediatricians. STUDY DESIGN,
SUBJECTS, METHODS: IRB approved 18-question survey was administered to members of
the Louisiana Chapter of the American Academy of Pediatrics. RESULTS: We received
116 responses (response rate: 15.9 percent );. 104 respondents (89.66 percent );
routinely recommend/offer HPV vaccine, 6 (5.17 percent ); occasionally or only at
caregiver request, and 6 (5.17 percent ); do not offer the vaccine. 17 (15.5
percent ); reported having no awareness of the link between oropharyngeal cancer
and HPV, and only 50 (45.9 percent ); had knowledge that HPV-related
oropharyngeal cancer incidence was increasing. Strength of recommendation for
males and knowledge of HPV-related oropharyngeal cancer were not associated with
years in practice, practice type or patient population served. CONCLUSIONS:
Increased awareness regarding HPV-related oropharyngeal cancers among primary
care providers may increase HPV immunization rates, especially in males.
PMID- 28414660
TI - A Mullerian Cyst Resected From the Posterior Mediastinum.
AB - Differential diagnoses of mediastinal masses are often based on the anatomic
locations. Traditionally the posterior mediastinum has been home to esophageal
and neurogenic cysts, but a new entity has been found to be prevalent since its
initial report in 2005: the Mullerian cyst. We present a 49-year-old with history
of cough who was found to have such a mass. We will discuss the surgical outcome
and the details of this interesting entity. The literature pertinent to this type
of cyst will be evaluated. In all cases reported, the literature demonstrates
that surgical removal results in uneventful follow-up with no evidence of
malignancy or cyst recurrence.
PMID- 28414661
TI - Delayed Presentation of Tuberour Sclerosis Complex in Adult Women.
AB - INTRODUCTION: Tuberous sclerosis complex (TSC); is an autosomal dominant disorder
characterized by the formation of hamartomatous lesions in multiple organs, with
a birth incidence of around one in 10,000. Although it usually manifests itself
in early life, we present a case of an adult woman who we diagnosed with TSC.
CASE: A 27 year old woman presented to Emergency Department with worsening right
flank pain and progressive dyspnea. Physical examination findings revealed
Shagreen patches and multiple angiomyolipomas of the skin. Computed tomography
scan of the chest and abdomen was remarkable for pulmonary
lymphangioleiomyomatosis and renal angiomyolipomas. Brain imaging revealed
multiple subependymal nodules and cortical dysplasias. Subsequent genetic testing
later confirmed pathogenic mutation in the TSC2 gene and patient was referred for
Genetic counseling and further management. DISCUSSION: Clinical features of TSC
continue to be the principal means of diagnosis, with the inclusion of
identification of a pathogenic mutation in TSC1 and TSC2 as an independent
diagnostic criterion. Affected patients may present early in life with the
classic triad of seizures, intellectual disability, and cutaneous angiofibromas,
but some findings, notably renal angiomyolipomas and pulmonary
lymphangioleiomyomatosis (LAM);, emerge later, placing adults with undiagnosed
TSC at increased risk for morbidity and mortality. Recent advances in the
treatment of TSC highlight.
PMID- 28414662
TI - Weil's Disease from a Local New Orleans Bar.
AB - INTRODUCTION: Leptospirosis is a zoonotic infection that typically presents with
fever, myalgias, nausea, and vomiting after contact with contaminated waters or
infected animals (typically rodents); and their excrements. Conditions favorable
to the transmission of leptospirosis are common in LA and, without treatment,
leptospirosis can lead to both liver and renal failure, meningitis, pulmonary
hemorrhage and ultimately death. CASE: A 56 year old woman with no past medical
history presented to the Emergency Department with weakness, myalgias, jaundice
and decreased urine output for one week. On arrival, she appeared septic with a
heart rate of 130 and fever. Her exam was significant for significant jaundice
and diffuse abdominal pain. Laboratory studies were notable for WBC 14,
hemoglobin of 12 and platelet count of 63. Creatinine was 8.5mg/dL with a blood
urea nitrogen of 96mg/dl. Total bilirubin was 19.4mg/dL and direct bilirubin was
13.7mg/dL. AST/ALT were 69/38 U/L, respectively and the alkaline phosphate was
160U/L. The patient was admitted to the hospital medicine wards for sepsis and
multi-organ failure. She was started on broad spectrum antibiotics but her
clinical condition continued to worsen with progressive decline in her hemoglobin
and thrombocytopenia and worsening liver failure. She quickly became anuric
necessitating dialysis and developed respiratory distress with bilateral
pulmonary infiltrates and hemoptysis. Additional history was obtained from her
employer that she works at a local New Orleans bar and had been cleaning out rats
from the kitchen. Leptospirosis antibody was sent, which returned as positive.
Her antibiotics were de-escalated to IV Ceftriaxone. She made a slow recovery
over the next two-week period. DISCUSSION: Since 1987, there has been an average
of 3 cases of Leptospirosis diagnosed per year, most of which have been from
southeast LA. This case illustrates the importance of considering the diagnosis
of Leptospirosis and Weil's Disease in patients in the southeast region of LA who
present with multi-organ failure. In addition, our patient's occupational
exposure was key to her diagnosis which emphasizes the importance of a detailed
history in clinical decision making and patient outcomes.
PMID- 28414663
TI - Not Another ACS Rule Out.
AB - CASE: A 50 year old African-American woman with diabetes, hypertension, and
hyperlipidemia presented with progressively worsening retro-sternal chest pain,
exacerbated by activity and relieved by rest. She also endorsed a thirty-pound
unintentional weight loss, and dysphagia. She was dysarthric with left-sided
Bell's Palsy and a palpable left axillary lymph node. She had been evaluated at
several hospitals in the previous months for similar typical chest pain. Her
troponin values were normal, and an EKG showed T-wave inversions in leads I and
aVL. On echocardiography, her ejection fraction was 45 percent with anterolateral
hypokinesis. She was treated for NSTEMI, and an angiogram showed 95 percent
stenosis of the right coronary artery. A modified barium swallow study revealed
weakened swallowing with aspiration of thin liquids. An MRI Brain demonstrated
scattered T2/ FLAIR hyper-intense foci in the subcortical white matter and focal
meningeal thickening. ANA, dsDNA, ANCA, and Lyme antibodies were all negative,
and a chest CT showed hilar lymphadenopathy. Cardiac MRI demonstrated scattered
foci of delayed enhancement in the mid-myocardium and sub-epicardium without
infarction. An endobronchial biopsy of hilar lymph nodes showed two small
epithelioid granulomas, consistent with Sarcoidosis. She was started on high-dose
corticosteroids with rapid improvement. A repeat modified barium swallow study
was normal and a repeat echocardiogram demonstrated recovered ejection fraction
of 55 percent with improved wall motion in the septum and apex. Additionally, her
left-sided Bell's Palsy and dysarthria improved after several days of therapy.
DISCUSSION: To our knowledge, this report is the third case of multi-organ
Sarcoidosis presenting as ACS. This case depicts the simultaneous presentation of
neurologic, pharyngeal, pulmonary, and cardiac Sarcoidosis. Myocardial
involvement in Sarcoidosis is rare and usually presents as conduction
abnormalities with arrhythmia rather than ACS. Though her symptoms were
consistent with Sarcoidosis, she had multiple risk factors for coronary
atherosclerosis including diabetes, hypertension, and hyperlipidemia. This case
highlights the importance of including Sarcoidosis in the differential diagnosis
for patients with recurrent typical chest pain of uncertain etiology.
PMID- 28414664
TI - Gonococcal Endocarditis: The Gift That Stops Giving! An Uncommon Presentation of
a Common Disease.
AB - INTRODUCTION: Gonorrhea is the 2nd most common sexually transmitted disease in
the US with 800,000 cases of gonorrhea each year. Disseminated gonorrhea
infection occurs in 0.5 percent - 3 percent of these patients and is more
frequent in woman younger than 40 years of age. CASE: A 36 year old woman with a
history of polysubstance abuse presented with 10 day history of feeling generally
unwell. At presentation, vitals were remarkable for tachycardia and hypotension.
Physical exam was remarkable for conjunctival pallor, bibasilar crackles, and
tachycardia with grade III/VI systolic murmur loudest over the 2nd inter-costal
space and loudest with expiration. No skin lesions were noted. Labs demonstrated
leukocytosis (WBC 20,200 with 84 percent neutrophils);, anemia (Hb 6.7);,
thrombocytosis (platelets 423 k/uL);, abnormal liver function tests (alkaline
phosphatase 239 IU, AST 151 IU ALT 71 IU, albumin 2.5g/dL);, PT/INR 17.1/1.5.
Troponin 0.42, BNP 823, D-dimer 619, and a urine drug screen that was positive
for benzodiazepines, opiates, barbiturates, amphetamine, and THC. Hep panel and
HIV were negative. Chest radiograph showed mild cardiomegaly and early
interstitial edema. The patient was placed on broad spectrum antibiotics and
given adequate fluid resuscitation and blood products. Blood cultures grew
Neisseria gonorrhoeae. 2D ECHO showed a large pedunculated/mobile echo density
adherent to the non-coronary and lefts cusps of the aortic valve. Proximal aortic
root and aorto-mitral continuity were thickened, consistent with aortitis and/or
abscess formation. Initial EKG on arrival showed junctional tachycardia which
progressed into complete heart block. Cardiology was consulted and a pacemaker
was placed emergently. However despite all aggressive measures the patient died
of cardiac complications. DISCUSSION: Endocarditis is a rare complication of
disseminated gonorrhea, occurring in only 1-2 percent of patients with
gonoccocemia. The aortic valve is most commonly affected. Valve replacement is
warranted in cases with severe dysfunction. Mortality remains around 19-20.
Neisseria gonorrhoeae endocarditis should be included in the differential
diagnosis in sexually active patients with endocarditis.
PMID- 28414665
TI - A Case of Early Neurosyphilis.
AB - INTRODUCTION: Neurosyphilis is an infection of the central nervous system by
Treponema pallidum, which can occur after the initial syphilis infection.
Although commonly associated with late stage disease, patients with early
neurosyphilis may present with acute syphilitic meningitis, meningovascular
syphilis, or uveitis. CASE: A 28 year old man with a past medical history of HIV
(CD4 364);, and recent diagnosis of uveitis presented to the Emergency Department
with a positive RPR result. His visual acuity had been gradually declining over
the past few months. He denied painless or painful ulcerating lesions on his
penis, or scrotum, difficulty concentrating, dermatitis on the soles/palms, or
difficulty with proprioception. Physical exam was notable for atrophic
hyperpigmented polycyclic, annular plaques and patches along the hairline as well
as several areas of confluent hyperpigmented polycyclic plaques and nodules on
the patient's face, back, left arm, and right posterior leg. Fundoscopic exam
revealed bilateral posterior uveitis and chorioretinitis. Evaluation of
cerebrospinal fluid revealed a lymphocytic pleocytosis with a positive VDRL and
FTA-ABS. Aqueous crystalline penicillin G was initiated for treatment of early
neurosyphilis. Within six hours of beginning the infusion, the patient had a
documented temperature of 101.8 degrees F, heart rate of 128 beats per minute,
blood pressure 142/84, with generalized malaise and headache. Fever and
tachycardia resolved over the next 12 hours, with weakness and headache resolving
within 1-2 days. His symptom complex was consistent with the Jarisch-Herxheimer
reaction. Histopathology of skin biopsy of the back showed perivascular
inflammation and rare spirochetes, consistent with secondary syphilis. The
patient completed 14 days of aqueous crystalline penicillin G and was discharged
after receiving the first of three benzathine penicillin injections. DISCUSSION:
The initial manifestations of syphilis in this patient were posterior uveitis and
pruritic skin plaques. His diagnosis should be appropriately classified as
secondary syphilis with concomitant symptomatic early neurosyphilis, requiring 14
days of aqueous crystalline penicillin G. This type of presentation is not
specific to immunocompromised populations and must be considered even in the
general population. Making the diagnosis of early neurosyphilis, regardless of
stage, is critical, as it necessitates a longer duration of treatment.
Furthermore, clinicians should be reminded of the profound immunologic reaction,
Jarisch-Herxheimer, which may occur when treating any treponemal disease.
PMID- 28414666
TI - Just a "Puff of Smoke".
AB - CASE: A 44 year old woman with a history of stroke s/p aneurysm clipping,
seizure, and substance abuse was brought to the hospital after a family member
received a call from her friend saying she was acting unusual and may have had a
seizure while hanging out on the street. At her baseline, she needed modest
assistance in daily activities after her CVA and conversed without issue. Her
mother died of a stroke. On exam the patient was afebrile, normotensive with mild
tachycardia to 110. The patient moved all her extremities but was lethargic,
agitated, responded to pain but would not follow commands and moaned nonsensical
speech. Labs were unrevealing with mild leukocytosis (WBC: 11.7 * 109/L);, normal
metabolic panel, ammonia, glucose, and a negative urine toxicology. Initial
computed tomography (CT); of her head demonstrated atrophy with large area of
encephalomalacia in Left middle cerebral artery (MCA); area. Repeat CT, 1 day
later showed edema and sulcal effacement in the right occipital, posterior,
temporal, and posterior parietal lobes with evolving infarct in right posterior
cerebral artery (PCA); and right MCA territories. CT angiogram showed occlusion
of the clinoid segments of both internal carotid arteries, consistent with
Moyamoya pattern of collateral flow. Neurosurgery was consulted and recommended
cerebral bypass. The patient was unable to consent for surgery and her closest
relative refused surgery. The patient received supportive therapy with minimal
improvements in word findings/ communication and no improvement in inability to
perform daily activities. She was accepted to inpatient stroke rehab upon
discharge. DISCUSSION: Moyamoya disease is a rare vascular condition which leads
to progressive stenosis of the internal carotid arteries through wall thickening
of the associated arteries which leads to progressive strokes and the development
of collateral vessels. Moyamoya is a Japanese term for a "puff of smoke" which
describes the appearance on imaging of the small collateral vessels that develop
around the progressively blocked arteries. There is a hereditary association and
our patient's mother likely had the disease as well. The prognosis is poor and
the disease will lead to a cognitive decline with associated CVAs. Treatment
includes cerebral revascularization or bypass. The case highlights the need for
early diagnosis, as our patient was too debilitated to make medical decisions for
treatment at the time of her diagnosis.
PMID- 28414667
TI - The Mysterious Case of Dyspnea.
AB - INTRODUCTION: Dehiscence of a mitral valve annuloplasty ring is a rare occurrence
that often manifests as mitral regurgitation and heart failure. We present a case
of mitral ring dehiscence which was initially unrecognized by standard 2
dimensional transthoracic echocardiography (2D TTE); and 2-dimensional
transesophageal echocardiography (2D TEE);. CASE: A 65-year-old woman was
referred to Cardiology clinic for evaluation of dyspnea. Her history included
tobacco abuse, atrial fibrillation status post pulmonary vein isolation,
nonischemic cardiomyopathy, and prior mitral valve repair with annuloplasty ring
for rheumatic valvular disease. She had been asymptomatic post-surgery. Physical
examination, cardiac rhythm and initial ischemic workup were unremarkable.
Pulmonary function tests revealed moderate emphysematous type obstructive lung
disease. A 2D TTE demonstrated moderate mitral regurgitation with normal left
ventricular function. In right heart catheterization, large v waves were noted
and 2D TEE also revealed severe mitral regurgitation. On 2D TEE, the mitral valve
annuloplasty ring was visible above the native anterior mitral valve leaflet.
Color Doppler flow estimated the effective regurgitation orifice area of 0.4cm2
using the proximal isovelocity surface area method and regurgitant volume of 58
cc, consistent with severe mitral regurgitation. A "floating mitral ring" and
dehiscence measuring 1 cm in diameter were seen on high resolution three
dimensional reconstruction resulting from the detachment of the ring from the
weakened posterior annulus. Based on these findings patient was referred to
cardiothoracic surgeon for re-do mitral valve surgery. DISCUSSION: This was a
perplexing case as the patient's dyspnea could be explained by many disease
processes including atrial fibrillation, mitral regurgitation and chronic
obstructive lung disease. The standard imaging modalities did not help us to
formulate a diagnosis. 3D TEE provided invaluable and unparalleled information of
mitral valve pathology. Annuloplasty ring dehiscence is a well described
complication of mitral valve repair and should always be considered in
symptomatic patients.
PMID- 28414668
TI - Autoimmune Diabetes Presented with Diabetic Ketoacidosis Induced by Immunotherapy
in an Adult with Melanoma.
AB - INTRODUCTION: Immunotherapy has been approved for treatment of melanoma.
Autoimmune endocrinopathies have been reported in trials involving immunotherapy
but autoimmune diabetes has not been definitively linked to them. Here we
describe a case of autoimmune diabetes presenting with DKA after receiving
combined immunotherapy with anti-CTLA4 and anti-PD1 monoclonal antibodies. CASE:
A 47year old gentleman with metastatic melanoma presented to our institution with
confusion, abdominal pain and decreased oral intake. The patient had a history of
diabetes on metformin which was discontinued two years prior. He was started on
Novilumab/Iplimumab for metastatic melanoma. He had received two cycles of
immunotherapy and treatment was initially well tolerated. However, eight days
after the second cycle the patient developed lethargy, confusion, vomiting and
abdominal pain. CT of the head was negative for intracranial abnormalities and
without evidence of brain metastasis. His laboratory results included: serum
sodium 126 mmol/L, potassium 6.7 mmol/L, BUN 55 mg/dL, creatinine 3.5,
bicarbonate 5 mmol/L, chloride 94 mmol/L, albumin 3.2 g/dL. Serum beta
hydroxybuterate was elevated (4.7 mmol/L, N: 0.0-0.5 mmol/L) and the calculated
anion gap was 43 mmol/L. Serum lipase elevated (535 u/L, N: 4-60 u/L). The
diagnosis of diabetic ketoacidosis was made and he was started on intravenous
fluids and insulin therapy. Given his history of metastatic melanoma, his DKA was
initially thought to be secondary to pancreatic metastasis especially considering
the elevated lipase level. A non-contrast CT of the abdomen showed no evidence of
pancreatic metastasis. Interestingly, further investigation identified high serum
titers of anti-glutamic acid decarboxylase (anti-GAD) antibodies (0.43 nmol/L, N:
less than 0.02 nmol/L), a low C-peptide level (0.2 ng/ml, N: 0.9-5.5 ng/ml),
supporting an autoimmune etiology of the diabetes. Other islet autoantibodies
were not elevated and his Hemoglobin A1C was 8.0 percent . DISCUSSION: There are
few case reports about diabetes and immunotherapy. Autoimmune mechanism was
suggested as the culprit, although not all cases reported with positive
antibodies. Moreover, it is unlikely that patient developed latent autoimmune
diabetes (LADA); and not related to immunotherapy due to the course of LADA is
quite more gradual and our patient presented with acute DKA few days post the
second cycle. Physicians and patients should be aware that autoimmune disorder
such as DKA may be a rare but important immunotherapy related adverse events.
PMID- 28414669
TI - A Case of Hepatosplentic T Cell Lymphoma - A Rare, Aggressive Tumor of the Young.
AB - INTRODUCTION: Hepatosplenic T-cell lymphoma (HSTCL); is an unusual entity first
described in 1990 that predominantly affects middle-aged men and is classified by
WHO under peripheral T-cell lymphomas. We present a 26-year-old man with HSCTL
treated with a non-CHOP regimen. CASE: A 26 year old immigrant from Cameroon
without significant past medical history presented with abdominal discomfort that
was first noted 1 month prior at which time he was elbowed in abdomen during a
basketball game. His abdominal discomfort continued to gradually worsen and was
associated with nausea, vomiting, early satiety and decreased appetite. He
developed subjective fever, chills, night sweats, fatigue and epistaxis 3 days
prior to presentation. CBC with differential revealed WBC 8 x 103/ul, RBC 4.50 x
103/ul, Hemoglobin 12.9 mg/dl, Hematocrit 38.2 percent , Platelets 30 x 103/ul,
elevated monocytes and nRBC's. EBV serology was positive for VCA IgG and Nuclear
antigen Antibody IgG, indicating past infection. Abdominal CT revealed marked
hepatosplenomegaly with displacement of abdominal viscera. PET revealed
heterogeneously increased FDG uptake in liver and spleen. Bone marrow showed
increased cellularity, increased atypical lymphocytes with clustering, and
sinusoidal infiltration. Lymphoid cells mainly expressed CD2, CD3 and CD8. Cells
were negative for TdT, CD1a, and increase in Ki-67 expression. Bone marrow flow
cytometry revealed predominance of atypical gamma/delta T cells. Cytogenetics
revealed normal male karyotype. Based on imaging, bone marrow, and flow
cytometry, diagnosis of HSCTL was made. The patient was treated with 4 cycles of
Ifosfamide, Carboplatin and Etoposide (ICE);. PET showed complete resolution of
uptake in liver and spleen. Repeat bone marrow showed no residual disease. He
underwent splenectomy and pathology revealed no evidence of residual T-cell
lymphoma. The patient then underwent autologous SCT with BEAM (Carmustine
Etoposide-Cytarabine-Melphalan); conditioning. He remains in remission after
transplantation. DISCUSSION: Although HSTCL is rare, recognition is important as
it is aggressive, refractory to conventional therapies, and carries a uniformly
poor prognosis. Conventional therapy consists of CHOP (cyclophosphamide
doxorubicin-vincristine-prednisone); with or without autologous stem cell
transplantation (SCT);. A novel approach reported by Hoss et.al with a non-CHOP
induction therapy with or without splenectomy followed by autologous SCT may have
better outcomes as demonstrated with our case.
PMID- 28414670
TI - Diulafoy's Lesion - An Uncanny Etiology of Gastrointestinal Bleed.
AB - INTRODUCTION: Dieulafoy's lesion is a relatively rare, but potentially life
threatening, condition. It accounts for 1-2 percent of acute gastrointestinal
(GI); bleeding. CASE: A 99-year-old woman was initially admitted due to left
lower extremity cellulitis related to chronic venous stasis ulcer and was
receiving broad-spectrum IV antibiotics. Upon admission to the medical floor, she
had an episode of hematemesis and multiple bowel movements with black-tarry
stools. The patient denied chronic non-steroidal anti-inflammatory drug use. Her
past medical history was significant for dyslipidemia and remote history of colon
cancer status post colon resection. Home medications included atorvastatin 20 mg
and aspirin 81 mg. Digital rectal exam demonstrated melenic stool in the rectal
vault. Hemoglobin and hematocrit on admission were noted to be 12.1 g/dl and 40.7
percent respectively which dropped to 8.1 g/dl and 28.3 percent following her GI
bleed. A rise on BUN was also noted from 14 mg/dl to 34 mg/dl. Platelets and INR
were normal. She received fluid resuscitation with 2 liters of crystalloid and a
total of 2 units of pack red blood cells. Emergent EGD revealed a protruding and
oozing vessel surrounded by normal gastric mucosa located at the greater
curvature of the stomach body. The lesion was covered by a prominent fresh clot,
which was cleared. Endoscopic hemostasis was achieved with a combination of
epinephrine injection followed by BI-CAP electrocautery. The patient had an
uncomplicated post-operative course and hemoglobin remained stable. DISCUSSION:
Given this patient's clinical presentation, an upper GI bleed was suspected.
Based on the patient's advanced age and history of previous history of colon
cancer, the initial differential diagnosis included peptic ulcer disease versus a
GI malignancy. However, her EGD findings were consistent with a Dieulafoy's
lesion. Dieulafoy's lesions are twice as common in men as compared to women.
These lesions can occur in any age group are diagnosed more frequently in the
elderly population. Dieulafoy's lesions should be included in the differential
diagnosis of obscure GI bleeding in all age groups.
PMID- 28414671
TI - Three's a Crowd - An Extremely Rare Case of Cor Triatriatum Dexter.
AB - INTRODUCTION: Cor triatriatum is a congenital cardiac anomaly in which the left
(sinister) or right (dexter) atrium is divided into two compartments by residual
embryonic tissue, resulting in a tri-atrial heart. As cor triatriatum dextrum can
present clinically in various ways and have multiple associated cardiac
anomalies, this report attempts to contribute to what is known about this
exceedingly rare disorder. CASE: A 40 year old Hispanic man with a medical
history of gastritis presented with complaints of palpitations, dizziness and
bilateral lower extremity edema. He was found to have atrial fibrillation and new
onset heart failure. The patient was admitted for rate control and further
evaluation, which revealed several cardiac anomalies. Initial 2D echocardiography
demonstrated severe right atrial enlargement, right ventricular hypertrophy and
an engorged coronary sinus, which prompted further assessment of the patient's
cardiovascular anatomy. Transesophageal echocardiography (TEE) revealed a
severely enlarged, septated right atrium with a possible unroofed coronary sinus
and a small patent foramen ovale (PFO). Left- and right-heart catheterization
established a coronary-cameral fistula between the right coronary artery (RCA)
and right atrium, as well as left-to-right shunt. The patient improved clinically
with conservative management including diet modification, furosemide and digoxin
for fluid and rate control, and was referred to cardiothoracic surgery for
further evaluation. DISCUSSION: Cor triatriatum dextrum is an extremely rare
cardiac condition: In high-volume echocardiographic laboratories, prevalence is
less than 0.01 percent. This case highlights the association between cor
triatriatum and other congenital cardiac anomalies, including persistent left
superior vena cava with an unroofed coronary sinus, PFO and left-to-right shunt;
all of which were found in this patient. While cases of cor-triatriatum sinistrum
often require correction in infancy (due to left sided heart failure, pulmonary
edema and cyanosis), cor-triatriatum dextrum is sometimes diagnosed in adulthood
due to the lack of left heart and pulmonary involvement.
PMID- 28414672
TI - A Strong and Fortuitous Case of Dyspnea.
AB - CASE: A 48 year-old man with no past medical history was sent to our emergency
department (ED); from a primary care clinic for hypertensive urgency of 200/130.
The man reported an intermittent non-productive cough of approximately one year's
duration and worsening dyspnea on exertion and orthopnea over the last month with
lower extremity swelling. Of note, he emigrated from Honduras twenty years ago.
Blood pressure normalized with administration of Lasix in the ED. Physical exam
revealed rales in lung bases bilaterally, jugular venous distension, lower
extremity pitting edema with serpiginous patches of erythema and excoriation, and
a cardiac gallop. Labs showed peripheral eosinophilia, thrombocytopenia, elevated
creatinine, hyperbilirubinemia, hyperglycemia, and mild transaminitis.
Transthoracic echocardiogram revealed a dilated left ventricle with global
hypokinesis and severely depressed systolic function with an ejection fraction
less than 15 percent . The patient was diuresed, and subsequent left and right
heart catheterizations were normal. CT chest showed a small nodule in the right
upper lobe. Tests for Coccidiosis, Trypanosoma cruzi, and Mycobacterium
tuberculosis were negative; however the acid fast bacilli culture grew
Mycobacterium fortuitum. A Strongyloides stercoralis antibody test was positive,
and the patient was treated with two doses of oral ivermectin with one dose of
intravenous ceftriaxone, and discharged. Two months later, his eosinophilia
resolved, but he remained symptomatic with productive cough and weight loss, and
was started on an outpatient course of oral ciprofloxacin and trimethoprim
sulfamethozole for M. fortuitum. DISSCUSION: Strongyloides-infected patients may
carry the parasite for years without prominent symptoms. Endemic throughout South
America, Strongyloides persists in its hosts through a lifecycle of
autoinfection, which, over time, increases parasite burden and can lead to a
hyperinfection syndrome whereby filiariform larvae penetrate organ tissue, most
commonly: heart, central nervous system, lungs and liver. We suspect chronic
eosinophilia and disseminated filiaria to be the etiology of the non-ischemic
dilated cardiomyopathy in this patient. Standard treatment of strongyloidiasis is
ivermectin, however, mortality owing to transient bacteremia in the setting of
hyperinfection syndrome is high. Therefore, bacteremia prophylaxis with gram
negative rod coverage should be considered before antiparasitic agent initiation.
PMID- 28414673
TI - Purulent Pericarditis Due to an Infected Pacemaker Lead.
AB - INTRODUCTION: Intravenous drug users have a substantially increased risk of
infective endocarditis, especially in the setting of implanted cardiac devices.
Purulent pericarditis is a rare occurrence that can occur iatrogenically or
through direct or hematogenous spread. CASE DESCRIPTION: A 75 year old man with a
past medical history significant for hepatitis C, IV drug abuse, and sick sinus
syndrome status post pacemaker was brought in by EMS with a chief complaint of
diaphoresis and chest pain. Initial EKG revealed atrial fibrillation with ST
elevations in multiple leads. The patient was taken urgently to the cardiac
catheterization lab due to concern for STEMI. Left heart catheterization revealed
nonobstructive CAD; bedside echo was significant for a pericardial effusion and a
pacemaker lead vegetation. CT of the chest revealed extension of the ventricular
pacemaker lead through the anterior right ventricular wall and pericardium and
into the pleural cavity. Cardiothoracic surgery performed a pacemaker removal as
well as pericardial window due to early tamponade; approximately 900 mL of
purulent fluid was drained from the pericardial space. The patient was septic
with initial blood cultures growing MSSA. He was also found to have multiple
other foci of infection including a left-sided pleural effusion and a perihepatic
fluid collection, both of which were drained and also grew out MSSA. The patient
initially improved on antibiotics after his pacemaker removal and drainage of the
infected fluid collections. However, several days after the pacemaker removal he
gradually became more bradycardic; due to his multiple comorbidities and active
infection, he was not a candidate for a replacement implanted pacemaker. He
became profoundly bradycardic and hypotensive overnight and died despite the use
of multiple pressors to maintain his blood pressure as well as transcutaneous
pacing to maintain his heart rate. DISCUSSION: Purulent pericarditis has become a
relatively uncommon occurrence since the development of effective antibiotics.
This case illustrates a rare example of purulent pericarditis and cardiac
tamponade secondary to the extension of an infected pacemaker wire through the
pericardium and into the thoracic cavity. The presence of multiple other infected
fluid collections in this case also illustrates the need to thoroughly assess for
secondary foci of infection in cases of bacterial endocarditis.
PMID- 28414674
TI - A Clot (Possibly); Due to Loss of TNF-alpha Supression.
AB - INTRODUCTION: Inflammation and venous thrombosis enjoy a close Relationship. We
present a patient who had multiple DVTs following the discontinuation of anti-
TNF-alpha therapy. CASE: A 34 year old African American female with a history of
multiple DVT's, miscarriages, and reported Crohn's disease presented with
shortness of breath. In the Emergency Department, CTA showed bilateral pulmonary
emboli. The patient had been off adalimumab for one year and reported abdominal
pain with 6-7 non-bloody bowel movements daily. She had been prescribed lovenox
for her unprovoked DVTs yet reported missing several doses prior to admission.
Following admission, she developed severe abdominal pain prompting an emergent CT
angiogram and she then developed a pulseless painful left lower extremity. CT
revealed a partially occlusive thrombus in the infra-renal abdominal aorta,
proximal left common iliac artery, and right renal artery with subsequent right
renal infarction. Following emergent vascular surgery to restore blood flow to
the left lower extremity, the patient received four days of plasma exchange and
high dose steroids for potential catastrophic antiphospholipid syndrome. Serology
for APLA was negative. The patient was discharged with lifelong anticoagulation.
DISCUSSION: The endothelial surface is a complex organ that works in concert with
the surrounding environment. Inflammation and thrombus formation is closely
associated. TNF-alpha can increase the expression of adhesion molecules,
specifically, tissue factor, on the surface endothelial cells and promote
thrombosis. Suppression of TNF-alpha expression by low molecular weight heparin
has been shown to inhibit the inflammatory cascade and reduce thrombus formation
in animal models. Clinical data is less clear. Interruption of TNF blockers has
been shown to increase the risk of DVT in patients with rheumatoid arthritis
undergoing orthopedic surgery. For patients with Bechet's syndrome, anti-TNF
agents appear help treat patients with pulmonary artery thrombosis. Further
review of anti-TNF-alpha therapy in our general medicine patient population may
disclose additional risks associated with discontinuation of these medications.
PMID- 28414675
TI - Case Report of Sarcoidosis as a Great Mimicker in Various Populations.
AB - INTRODUCTION: The prevalence of sarcoidosis varies as much as 1-40 cases per
100,000 depending on region and population. Sarcoid typically occurs in people
younger than 50 years old, with a peak incidence with ages between 20 and 40
years old. African Americans are 3 times more likely to develop sarcoidosis than
Caucasian Americans, and woman are more likely than men to develop sarcoidosis in
any ethnic group; nonetheless, it remains a valid differential across any
population. CASE: A 32 year old Hispanic man presented to the Emergency
Department with night sweats, fatigue, and 35 pound unintentional weight loss
over the last several weeks. He also reported a sore throat, occasional cough w/
yellowish sputum, and new onset dyspnea with exertion. He moved from Mexico to
the U.S. 20 years prior and last visited the country 7 yrs ago. He never smoked
and denied any TB exposure. His vitals at admit demonstrated tachycardia (pulse
108); and temperature of 99.4 ?F. He had coarse bilateral breath sounds on exam.
Serum chemistries were unremarkable. Chest radiograph demonstrated perihilar
fullness. Chest CT revealed enlarged mediastinal and perihilar LAD and airspace
consolidation in right middle and lower lobes bilaterally. The patient was
admitted to a negative pressure room w/ airborne precautions and RIPE therapy was
initiated. PPD and AFB's were negative. He underwent bronchoscopy and was
discharged on RIPE. Lung biopsy showed non-caseating granulomas. RIPE therapy was
stopped, and he was referred to ophthalmology to rule out uveitis. Cultures from
the procedure were negative for fungal growth, and he was started on prednisone
40 mg daily with taper 6 weeks later as his weight returned, night sweats
subsided, and dyspnea on exertion improved. DISCUSSION: Sarcoidosis should be
considered as a diagnosis in any gender of any racial or ethnic group. Sarcoid is
a great mimicker of many serious illnesses including malignancies such as
lymphomas, TB and atypical mycoplasma, fungal infections, and other granulomatous
diseases, and other autoimmune disorders such a hypersensitivity pneumonitis.
Diagnosis requires patient investigation and careful analysis of these
differentials.
PMID- 28414676
TI - Pheochromocytoma of the Organ Zuckerkandl.
AB - INTRODUCTION: Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);,
are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal
paragangliomas may arise in the sympathetic or parasympathetic paraganglia and
more rarely in other organs. One of the most common extra-adrenal sites is in the
organ of Zuckerkandl, a collection of chromaffin cells near the origin of the
inferior mesenteric artery or near the aortic bifurcation. The following is a
case of a patient with resistant hypertension secondary to an extra-adrenal
paraganglioma in the organ of Zuckerkandl. CASE: The patient is a 43 year old man
with a history of depression, type 2 diabetes mellitus, and hypertension who was
sent to the emergency department by his primary care physician for severely
elevated blood pressures. Patient also had diaphoresis, tachycardia, and a new,
fine tremor of his left hand. Upon presentation, the patient's blood pressure was
260/120 mmHg with a heart rate of 140 beats per minute. Plasma fractionated
metanephrines sent on admission revealed significantly elevated levels of total
plasma metanephrines (2558 pg/mL);, free metanephrine (74 pg/ml); and free
normetanephrine (2484pg/mL);. An I-123 metaiodobenzylguanidine (MIBG); scan
showed abnormal uptake in the lower abdomen at the level of the aortic
bifurcation. Patient was started on alpha-blockade, with subsequent addition of a
beta-blocker prior to surgery. Patient underwent surgical removal of the tumor
with pathology consistent with a paraganglioma. DISCUSSION: Pheochromocytomas and
paragangliomas are responsible for approximately 0.5 percent of cases of
secondary hypertension. Many different biochemical markers have been used to aid
in the diagnosis of PCC/PGL including plasma catecholamines, plasma
metanephrines, urine fractionated metanephrines, urine catecholamines, total
metanephrines and vanillymandellic acid. Definitive management of a PCC and PGL
involves surgical removal of the tumor. Finally, there should be a discussion
with each patient to determine if he or she should undergo genetic testing, as
studies show that approximately 25 percent of catecholamine producing PCCs and
PGLs are due to heritable genetic mutations.
PMID- 28414677
TI - A Rare Case of Tropical Pyomysitis Acquired on Vacation in a Healthy Male.
AB - INTRODUCTION: Pyomyositis has traditionally been considered a tropical disease.
Increasing prevalence has been observed in more northern climates, especially
with HIV, immunosuppression, and IV drug abuse as predisposing factors.
Pyomyositis has the tendency to mimic other conditions, such as muscle contusion,
necrotizing fasciitis, or septic arthritis. The rarity of this disease and non
specificity of its symptoms often lead to delay in appropriate diagnosis and
treatment. CASE: 24-year-old man, seen 2 days prior in orthopedics clinic and the
Emergency Department for persistent gluteal pain thought to be due to right-sided
sciatica, was admitted following worsening pain, diffuse generalized weakness
with polyarthralgias and myalgias These symptoms were associated with night
sweats, shaking chills, and difficulty walking. Prior to onset of symptoms, the
patient vacationed in Cayman Islands and experienced a stingray bite on his right
hand as well as numerous cuts on rocks in stagnant waters. He was febrile with
WBC count of 18.7 K/ MUL and was found to have methicillin-sensitive
Staphylococcus aureus (MSSA); bacteremia. Magnetic resonance imaging (MRI); of
his lumbar spine on admission was unremarkable. Repeat MRI 4 days later showed
extensive inflammation within musculature with multiple abscesses around right
sciatic foramen and septic arthritis of the sacroiliac joint. The patient was
subsequently diagnosed with MSSA septic polyarthritis and required several
orthopedic procedures. Infectious and oncologic work up was unremarkable.
Transesophageal echocardiogram showed 0.3 cm x 0.5 cm aortic valve vegetation,
which was managed medically. Repeat MRI 11 days after initiation of appropriate
antibiotics and surgeries showed improvement in muscular edema. Based on the MSSA
susceptibilities, the patient was treated with 6 weeks of intravenous cefazolin
and 2 weeks of oral cephalexin thereafter. DISCUSSION: Awareness of tropical
pyomyositis in colder climates remains scarce, although cases have been reported
in immunosuppressed patients. However, in healthy patients, accurate history of
travel and trauma is important in evaluation for predisposing factors for
pyomyositis. Early antibiotic and appropriate surgical interventions are
imperative for management of this disease in order to prevent systemic toxicity,
dissemination of infection, and long-term debility.
PMID- 28414678
TI - What the Eyes Don't See, the Heart Does Grieve Over.
AB - INTRODUCTION: A 71 year old Peruvian woman presented with blurry vision and
bilateral eye pain and had evidence of bilateral endophthalmitis on eye
examination. Her past medical history was notable for multiple abdominal
surgeries within the preceding months, including an incarcerated inguinal hernia
repair which required an ileostomy placement, and cholecystitis requiring
cholecystostomy tube placement. Over her multiple long hospitalizations, she
developed bacteremia and fungemia on several occasions, with organisms including
Enterobacter cloacae, Klebsiella pneumoniae, Bacteroides fragilis, Pseudomonas
aeruginosa, Enterococcus faecium, and Candida albicans. On exam, she was febrile
and tachycardic. She had bilateral conjunctival injection, hypopyon, and severely
decreased visual acuity. She also had a III/VI harsh holosystolic murmur at the
apex. Her lungs were clear to auscultation. Transesophageal echocardiogram
revealed severe mitral regurgitation and a 16 x 15 mm mitral valve vegetation and
a perforated aneurysmal posterior mitral valve leaflet. The patient underwent
bilateral vitrectomy and was treated with flucytosine and ambisome. Blood and
vitreous humor cultures were obtained, but remained negative, likely due to being
drawn after the patient had been empirically treated with antifungals and
antibiotics. She continued to spike fevers and developed heart failure, but
refused valve replacement surgery as she wished to return to her home country.
DISCUSSION: A systemic source of infection should be sought in the presence of
bilateral endophthalmitis. In our case, we suspected seeding from endocarditis or
an intra-abdominal infection, given the patient history of multiple complicated
abdominal surgeries and recurrent bacteremia and candidemia. Based on the
vegetation's large size and bilateral endophthalmitis, we believed Candida was
the most likely culprit. Additionally, eye lesions observed during surgery
appeared consistent with fungal endophthalmitis. Candida is a rare but very
morbid cause of infective endocarditis. Arterial embolization and metastatic
infections such as endophthalmitis are more frequent in candidal endocarditis,
likely due to the generally larger vegetation size. Valve replacement should be
strongly considered regardless of other factors, as some studies have shown a
mortality benefit for antifungals and surgery compared to antifungals alone. In
cases in which valve replacement is not feasible, the patient should be kept on
lifelong suppressive antifungal therapy.
PMID- 28414679
TI - Misses Opportunity: TOF Diagnoses in 4th Decade of Life.
AB - CASE: A 40 year old woman with a history of HIV, congestive heart failure
secondary to an unknown congenital heart defect, and hypertension presented to
our emergency department with worsening edema. On room air, oxygen saturation was
55 percent . On 5L of oxygen via nasal cannula, oxygen saturation was 88 percent
. Physical examination was notable for central cyanosis, facial and lid edema, a
II/VI holosystolic murmur across right chest radiating to entire right back
hemithorax, decreased breath sounds at bases with pulmonary crackles, clubbing of
fingers and edema of bilateral lower extremities. The patient related lifelong
knowledge of a congenital heart defect, but had not been seen by a cardiologist
as an adult. She was asymptomatic, yet sedentary until one year ago when she had
the first of multiple hospitalizations for acute decompensated heart failure. A
chest x-ray showed massive cardiomegaly with right-sided calcified aortic arch
and patchy bilateral infiltrates. Transthoracic echocardiogram revealed severe
right ventricular hypertrophy, ventricular septal defect, overriding aorta, and
ejection fraction of 50 percent , consistent with unrepaired ToF. We utilized
multimodality imaging techniques including CT angiography and Cardiac MRI which
further defined her cardiac anatomy. Findings were consistent with unrepaired ToF
with pulmonary atresia. The pulmonary arteries arose directly from the aorta in a
confluent fashion via a large patent ductus arteriosus, major aortopulmonary
collateral artery. The arterialized pulmonary arteries were aneurysmal with
dissection and mural thrombus formation. DISCUSSION: This case illustrates how a
patient with a rare presentation of unrepaired ToF with pulmonary atresia can go
undiagnosed into adulthood. Early recognition utilizing a multimodality imaging
approach can lead to proper diagnosing and hopeful surgical repair which can
provide considerable improvement in functional status and long-term survival.
PMID- 28414680
TI - A Rare Cause of Abdominal Pain.
AB - CASE: A 54 year old woman with hypothyroidism presented with right flank pain
that began acutely one week prior to presentation. She was told initially she had
a urinary tract infection and treatment resulted in mild symptomatic improvement.
The pain returned and she presented to another Emergency Department (ED); and was
told the pain was due to constipation. She returned to the ED the next day when
her pain worsened and her labs were notable for WBC of 19,000/uL, BUN/Cr of
28/0.75 mg/dL, AST of 31 U/L, ALT of 92 U/L and total bilirubin of 0.6 mg/dL. RUQ
ultrasound was notable for dilation of the common bile duct. Given concern for
choledocholithiasis, she was started on cefepime and metronidazole. MRCP
demonstrated a distended gallbladder without stones and a small amount of
pericholecystic fluid. Also noted were two areas of increased signal in the right
kidney, concerning for neoplasia or infarction. Contrasted abdominal Computed
tomography showed a moderate size area of hypodensity, consistent with renal
infarct. Workup for embolic source of the infarction was unrevealing. Renal
artery angiogram demonstrated a spontaneous dissection of the superior branch of
the right renal artery. PCI was not performed due to risk of jeopardizing the
other vessels and so she was managed medically with rivaroxaban along with
hydrochlorothiazide and metoprolol succinate to keep her systolic blood pressure
below 140 mmHg. The morning after the procedure, the patient told the treatment
team that her grandson liked to jump from a height and she would catch him on her
right side. This was felt to be a likely etiology of her spontaneous dissection.
At the time of discharge, her pain was improved and repeat angiogram performed
eight weeks later noted healing of the dissection. DISCUSSION: Spontaneous renal
artery dissection is a rare cause of abdominal pain and often presents a
diagnostic and therapeutic challenge. This case highlights the importance of
considering alternate etiologies of localized abdominal pain when other common
pathologies have been excluded.
PMID- 28414681
TI - What Can Erode Through Lungs, Bone and Skin?
AB - CASE: A 51 year old African American Man without significant past history
presented with three weeks of persistent cough productive of copious yellow
sputum. He denied fevers, chills, hemoptysis, dyspnea, weight or appetite
changes, sick contacts, recent travel. On physical examination, the patient was
afebrile and appeared comfortable. He had decreased air entry of the left lower
lobe with dullness to percussion. A 5x3 cm fluctuant mass was incidentally found
on the left anterior chest wall at the level of the 11th rib with yellow
expressible exudate at which time the patient reported a minor trauma sustained 3
weeks prior. WBC count was 17,300/mcL. CT chest identified a peripherally
enhancing fluid-attenuation structure in the left lower lung measuring 11.8 cm x
11.3 cm x 9.6 cm. The collection appeared to be tracking out from the pleural
space to the exterior skin that corresponded to the site of the chest wall
swelling. There was also a focal lytic lesion of the adjacent ribs. He was
empirically started on Vancomycin, clindamycin and piperacillin-tazobactam.
CTguided aspiration failed because the material was too viscous to be aspirated;
a chest tube drained copious yellow exudate. Blood cultures and respiratory
cultures were negative. Gram stain of the purulent material demonstrated clusters
of branching gram positive rods. Pathology showed necrotic debris with clusters
of filamentous gram negative organism. Acid fast and Kinyoun stains were
negative. He was started on empiric Penicillin G for empyema necessitans with a
presumed etiology of actinomyces. Due to development of hypersensitivity drug
eruption from PCN, intravenous doxycycline was started for total of 14 days
followed by 6 months of oral therapy. Imaging four weeks after treatment showed
significant reduction in size of the lesion. Culture confirmed Actinomyces
israelii. DISCUSSION: Actinomyces are anaerobic gram positive commensals of the
oral cavity notorious to breach though tissue planes. Thoracic manifestations are
varied and can mimic malignancy. Astute microbiology and pathology tests are
necessary to make an early diagnosis and prevent invasive surgery as the organism
is a slow growing anaerobic bacteria. Excellent clinical and radiologic response
were noted in our case following treatment with chest wall drainage and
antibiotics thus avoiding invasive thoracic surgery.
PMID- 28414682
TI - A Left Main Coronary Artery Thrombus Presenting as a Non St Elevation MI.
AB - INTRODUCTION: Left main coronary artery (LMCA); thrombus with an acute myocardial
infarction identified with coronary angiography is a clinically rare condition
with an extremely high mortality rate. We present a case of LMCA thrombus that
presented as a non-ST elevation myocardial infarction (NSTEMI);. CASE: A 45-year
old woman with a history of tobacco use and hyperlipidemia presented with a
complaint of 10/10 "hard pain" across her chest radiating to her left shoulder
and breast which woke her from sleep. The pain was constant and severe, with no
alleviation with rest. She had not experienced anything like this before. Workup
revealed an upward trending troponin (1.9?8.98?9.79);, and an EKG with some
tachycardia but no ST elevation or T wave changes. Her CBC, CMP and coagulation
studies were unremarkable. A toxicology screen was positive for opiates and
benzodiazepines, medications she was on for pain and anxiety respectively. ACS
protocol was started with DAPT, LMWH, Statin, ACEi, and Beta-blocker. An
angiogram revealed a large thrombus in the LM coronary artery extending into the
aorta with concomitant 99 percent stenosis of distal LAD. 2D Echo w/ bubble
contrast was significant for PFO, akinetic apical inferior and anterior wall. The
mid antero-septum and apical lateral wall were hypokinetic. Interventional
Cardiology and CTS recommended conservative management with medical optimization
(Continue DAPT, heparin);, watchful waiting for the thrombus to resorb.
DISCUSSION: Left main coronary artery thrombosis (LMCAT); identified during
coronary angiography is a rare and challenging condition. It is a life
threatening condition with an approximate incidence rate of 0.8 percent . It is
thought to be secondary to plaque rupture with subsequent thrombus formation that
is associated with persistent hypercoagulable state, cocaine induced plaque
rupture or coronary vasospasm, post-partum state and embolization of intra
cardiac masses. The patient presentation can vary from sudden cardiac death to
STEMI, NSTEMI, unstable angina and cardiogenic shock. Standardized therapy has
not been developed due to the small number of reported cases.
PMID- 28414684
TI - Who Shot the Cannonballs? Extensive Lung Metastases in a 39 Year Old Man.
AB - CASE: A 39 year-old man presented to the emergency department complaining of a
cough of 2 months in duration. He also complained of weight loss of 20 pounds in
two months and night sweats over the same period. An x-ray of the chest was
performed and revealed innumerable lung nodules and masses. Computed tomography
of the chest and abdomen were subsequently performed which confirmed the masses,
but imaging did not reveal an obvious primary source. A testicular exam was
performed but no obvious abnormalities were noted. Because of his age as well as
the appearance of the lesions, a testicular ultrasound was then performed. The
ultrasound found evidence of a 1.5 cm hypoechoic mass on the right testicle with
dystrophic calcification in the interpolar region. Urology performed a right
radical inguinal orchiectomy. Pathology demonstrated a malignant mixed germ cell
tumor with seminoma and yolk sac components being prominent. He underwent four
cycles of etoposide, ifosfamide, and cisplatin. His last positron emission
tomography scan did not demonstrate active disease. DISCUSSION: Each year about
8700 men are diagnosed with testicular cancer. 75 percent of these occur between
the ages of 20 to 44, and the median age of diagnosis is 33. Testicular cancer
should be suspected when a young male presents with metastatic disease such as in
this case. In this patient, the genital exam was normal due to the small size of
the testicular mass, but he had significant metastatic lesions. When cannonball
metastases are seen on imaging, germ cell tumors and renal cell carcinoma should
be high in the differential diagnosis.
PMID- 28414683
TI - Recurrent Hypertriglyceridemic Pancreatitis (HTGP); and the Use of Insulin Drip
as Treatment.
AB - INTRODUCTION: Chronic pancreatitis by definition is a recurrent episode of acute
pancreatitis and is commonly associated with alcoholism in the US. Another cause
of chronic pancreatitis is hypertriglyceridemia (HTGP);, occurring in 1-5 percent
of cases. The incidence of HTGP is higher in patients with diabetes and HIV,
usually requiring triglyceride levels > 1000 mg/dL. CASE: A 33 year old man with
uncontrolled type 1 diabetes and recurrent pancreatitis, first diagnosed 5 years
prior, presented as a transfer from an outside hospital for a recurrent episode
of HTGP. He reported recurrent pain episodes, requiring 6-9 hospitalizations
within the last year for pancreatitis. He reported poor compliance with his
insulin regiment at home. Other home medications included gemfibrozil,
lisinopril, niacin, and omega-3 fatty acid. On transfer, his glucose was 296,
triglyceride level was >3600, and A1C of 12.4. Transfer report lab work showed a
triglyceride level >7000 and a lipase of 600. The patient had severe, diffuse
abdominal tenderness on examination. He was diagnosed with pancreatitis secondary
to hypertriglyceridemia due to a lipoprotein metabolism disorder and long
standing uncontrolled DM1. An intensive insulin drip was started on this patient,
with goals of correcting his TG to less than 500 along with lowering his glucose.
After 13 days, mostly on insulin drip, his TG decreased to 995 and pain was
controlled, eventually tolerating a diabetic diet. He was encouraged to modify
his diet and take his medications as directed at discharge. DISCUSSION: The
relationship between hypertriglyceridemia and pancreatitis is poorly understood.
In HTGP, a decrease in triglyceride concentration is a management priority. Rapid
triglyceride concentration lowering is managed by insulin or plasmapheresis. As
HTGP often presents in patient with uncontrolled diabetes, insulin is frequently
used as treatment to lower both blood glucose and triglycerides; insulin
decreases serum triglyceride levels by enhancing lipoprotein lipase activity and
inhibiting hormone sensitive lipase, accelerating metabolism and decreasing
adipocyte breakdown. Patients should be educated on the importance of compliance
with drug therapy and lifestyle modifications.
PMID- 28414685
TI - Association of State-Mandated Abstinence-only Sexuality Education with Rates of
Adolescent HIV Infection and Teenage Pregnancy.
AB - INTRODUCTION: Abstinence-only sexuality education (AOSE); is required in the
public school systems of many states, raising public health concerns and
perpetuating health disparities through school systems. This study aimed to
determine the correlations between state-mandated AOSE and the rates of
adolescent HIV and teen pregnancy. METHODS: Using publicly available data on all
50 United States' laws and policies on AOSE, states were ranked according to
their level of abstinence emphasis on sexuality education (Level 0 - Level 3);.
We calculated the relative proportion of Black students in public schools and the
proportion of families below the federal poverty line then ranked them by state.
We compared the states' ranks to the incidence of adolescent HIV and teen
pregnancy in those states to identify associations between variables. RESULTS:
The majority of states (~44 percent ); have legally mandated AOSE policies (Level
3); and adolescent HIV and teen pregnancy rates were highest in these Level 3
states. There were significant, positive correlations between HIV incidence rates
of 13-19 year olds, HIV rates of 20-24 year olds, teen pregnancy rates, and AOSE
level, with the proportion of the population that lives below the federal poverty
level, and whether they attended schools that had a greater than 50 percent of an
African American population. DISCUSSION: These data show a clear association
between state sexuality education policies and adolescent HIV and teen pregnancy
rates not previously demonstrated. Our data further show that states that have
higher proportions of at-risk populations, with higher adolescent HIV and teen
pregnancy rates, are more likely to also have restrictive AOSE policies. These
populations may be more likely to attend public schools where AOSE is taught,
increasing their risk for HIV and teen pregnancy. The World Health Organization
considers fact-based Comprehensive Sexuality Education a human right, and the
authors believe it is past time to end harmful, discriminatory sexuality
education policies in US public schools.
PMID- 28414686
TI - Severe Sepsis and Septic Shock Cases Meeting Guidelines Among Patients in a
University Hospital Setting.
AB - BACKGROUND: A diagnosis of severe sepsis or septic shock has been shown to
significantly increase mortality rate independent of other factors. Research has
revealed all cause hospital case fatality rates have declined yet the percentage
of severe sepsis cases continues to increase and age-adjusted mortality rates
from severe sepsis and septic shock has significantly increased during the same
time period. Patients with severe sepsis demonstrate ongoing mortality rate
increases for up to 2 years following hospitalization when compared to aged
matched controls of nonseptic patients. International guidelines with mortality
benefit for the management of severe sepsis and septic shock have been
illustrated in the latest surviving sepsis campaign. OBJECTIVE: The objective of
this study was to increase the percentage of patients admitted to the hospital
with a diagnosis of severe sepsis or septic shock who met guidelines based on
surviving sepsis campaign. METHODOLOGY: A retrospective chart review was
conducted for patients admitted to UHC from January 2016 to present to identify
cases with a diagnosis of severe sepsis or septic shock, and whether they met
guidelines set forth by surviving sepsis campaign both before and after an
intervention program which included interviews with providers failing to meet
protocol, educational sessions on guidelines to meet protocol, resident led
quality improvement workshops to address barriers to meeting protocol, and
development of an EMR power plan to assist providers on meeting protocol.
RESULTS: 139 cases with a diagnosis, or meeting criteria for, severe sepsis or
septic shock were identified during the period of 1/1/2016-9/30/2016 with an
average of 43 percent of total cases which met guidelines. Trend analysis
revealed increased compliance following resident lead intervention program with
31 percent and 49 percent before and after intervention, respectively. ICU data
is currently being analyzed for meeting guidelines and have not been included in
current data. The most common reason for failing guidelines was failure to obtain
or repeat lactic acid on time (46 percent ); and failure to give timely
antibiotics (22 percent );. CONCLUSIONS: The percentage of patients admitted to
the hospital with a diagnosis of severe sepsis or septic shock at UHC meeting
guidelines set forth by surviving sepsis campaign has improved following resident
lead intervention program. Intervention strategies to further improve compliance
with guidelines with a goal >60 percent are currently being analyzed.
PMID- 28414687
TI - Disseminated Cryptococcal Disease with Diffuse Pulmonary Infiltrates in a Non-HIV
Host.
AB - INTRODUCTION: We present a case of disseminated Cryptococcus in a non-HIV host,
where the primary manifestation was pulmonary with diffuse pulmonary infiltrates.
This patient was on high dose corticosteroids for autoimmune hemolytic anemia.
CASE: A 79 year old Caucasian man with a history of autoimmune hemolytic anemia
on 100 mg of prednisone daily, coronary artery disease s/p bypass surgery,
ischemic cardiomyopathy, chronic obstructive pulmonary disease, sleep apnea,
chronic kidney disease, and history of bilateral pulmonary emboli presented to
Hematology/Oncology clinic with symptoms of productive cough, worsening shortness
of breath, hemoptysis. Anticoagulation had been stopped due to symptoms. The
patient was referred to the emergency department from clinic where a chest CT
demonstrated numerous calcified lymph nodes and diffuses grand glass opacities
worse on the right and new compared to imaging from 6 months prior. The patient
was placed on empiric antibiotics for treatment of pneumonia after blood and
sputum cultures were obtained. Initial blood cultures grew Cryptococcus
neoformans in both sets. CSF obtained by Lumbar puncture was negative for
Cryptococcal. Serum Cryptococcal antigen titer was 1:2560. Infectious disease was
consulted and the patient was started on induction therapy with liposomal
Amphotericin B, followed by Fluconazole consolidation therapy. Hematology/
Oncology reduced the patient's prednisone dose gradually but further
complications attributed to corticosteroids eventually necessitated the need to
transition to Rituximab therapy. Follow up imaging on return to pulmonary clinic
demonstrated marked improvement in the bilateral infiltrates. DISCUSSION: This
patient was unique in that he demonstrated disseminated Cryptococcus but lacked
neurologic complications, which is often how disseminated disease is clinically
suspected. Blood cultures resulted positive for Cryptococcus and appropriate
antifungal therapy was initiated before other sites were affected. The patient
was HIV negative and not a post-transplant patient but was on high dose chronic
prednisone for his AIHA, and therefore immunosuppressed. Opportunistic and
atypical infections should be considered in all immunosuppressed patients to aid
in earlier diagnosis and prevention of further dissemination of disease and
further complications.
PMID- 28414688
TI - ECG Of The Month: Mental Disturbance for 4 days.
AB - A family brought their 61-year-old mother to the emergency department because for
4 days she had been confused, incoherent, and somnolent. She also had dysphagia,
dysarthria, diplopia, and had fallen out of bed. She had been in the hospital 3
weeks earlier for atrial fibrillation and an exacerbation of congestive heart
failure. She also carried a diagnosis of chronic obstructive pulmonary disease
and used an albuterol inhaler. She was obese (BMI of 45); and had adult-onset
diabetes mellitus. She had a 43 pack-year history of cigarette smoking but had
recently quit. Soon after arriving in the emergency department, she had an ECG
(Figure);.
PMID- 28414690
TI - Injectable Biological Treatments for Osteoarthritis of the Knee.
PMID- 28414689
TI - Radiology Case Of The Month: Mental Disturbance for 4 days.
AB - A 56 year old African-American man presented to the emergency department with
dyspnea and dysphagia with drooling. On his initial evaluation, disproportionate
obesity of the face, neck and shoulders were noted. The patient's history was
significant for obstructive sleep apnea, end-stage renal disease, alcoholic liver
disease, pulmonary hypertension and alcoholic cardiomyopathy. He had multi-decade
history of heavy alcohol abuse, but quit drinking two years previously.
PMID- 28414691
TI - Mr-Proadm Elevation Upon Icu Admission Predicts the Outcome of Septic Patients
and is Correlated with Upcoming Fluid Overload.
AB - BACKGROUND: Among septic patients admitted to the intensive care unit (ICU),
early recognition of those with the highest risk of death is of paramount
importance. We evaluated the prognostic value of Procalcitonin (PCT), mid
regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT
ProET 1) concentrations. METHODS: This was a prospective cohort study, which
included 173 septic patient admitted to one ICU. Blood samples for biomarker
measurements were obtained upon admission and on day 5. The predictive value of
each biomarker regarding the risk of death at day 28 was assessed. The fluid
balance was evaluated from admission to day 5. RESULTS: All cause ICU mortality
was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated
in the non-survivors than in the survivors upon day 1. This was especially true
for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET
1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The
best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR
proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI,
respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM
baseline levels and fluid balance over the 5-day period following ICU admission
were strongly correlated (Rho = 0.41; P < 0.001). CONCLUSIONS: In patients
admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of
short-term clinical outcome if compared with others. This could be related to its
ability to predict fluid sequestration.
PMID- 28414692
TI - Neuronal Fibers and Neurotransmitter Receptor Expression in the Human
Endolymphatic Sac.
AB - INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may
have multiple functions, including an ion-transport capacity comparable to the
kidney, an immunological capacity and a possible natriuretic capacity. Further,
there have been speculations of a yet undefined role in intracranial pressure
homeostasis. The anatomical location towards the sigmoid sinus would suggest a
possible endo- and/or paracrine signaling. However, neuronal connections may also
apply, but it remains very scarcely explored in the human ES. STUDY DESIGN: DNA
micro-arrays and immunohistochemistry were used for analyses of fresh human ES
tissue samples. METHODS: A total of 30 tissue samples from the human ES were
obtained during translabyrinthine surgery for vestibular schwannoma. Microarray
technology was used to investigate tissue sample gene expression, using adjacent
dura mater as control. The expression of genes specific for neuronal signaling
was determined and results for selected key molecules verified by
immunohistochemistry. Transmission electron microscopy was used for
ultrastructural analysis. RESULTS: For the transmission electron microscopy
analysis, a direct innervation of the ES was observed with unmyelinated fibers
imbedded in the ES epithelial lining. The microarrays confirmed, that several
molecules involved in neuronal signaling were found expressed significantly in
the ES DNA profile, such as the Cholecystokinin peptide and related receptors,
Dopamine receptors 2 and 5, vesicular monoamine transporter 2 (VMAT2), plasma
monoamine transporter (PMAT), and Serotonin 1D. All peptides were verified by
immunohistochemistry. CONCLUSIONS: Based on global gene expression profiling and
immuno-histochemical labeling, we conclude that the human ES expresses
neuropeptide receptors and monoamine transporters. Combined with the
ultrastructural demonstration of unmyelinated axons imbedded within the
epithelial lining, the findings suggest that neuro-signaling mechanisms are
involved in functions exerted by the ES.
PMID- 28414693
TI - Systematic Review on the Trial Period for Bone Conduction Devices in Single-Sided
Deafness: Rates and Reasons for Rejection.
AB - OBJECTIVE: To systematically review the literature to evaluate the trial period
of bone conduction devices (BCDs) for adult patients with single-sided deafness
(SSD). DATA SOURCES: The PubMed, Embase, and Cochrane Library databases were
searched from their inception up to August 15, 2016 for SSD, BCD, and their
synonyms. STUDY SELECTION: In total, 523 articles were retrieved, of which 12
satisfied the eligibility quality criteria. Our outcomes of interest were: 1) the
BCD implantation rejection percentage, 2) reasons to reject BCD implantation, and
3) possible prognostic factors predicting the trial outcome. DATA EXTRACTION AND
SYNTHESIS: At critical appraisal, six studies (n = 471 patients) scored a
moderate to high directness of evidence and a medium or low risk of bias and were
selected for data extraction. Due to heterogeneity between studies, pooling of
data for meta-analysis was not feasible. Therefore, results of studies were
summarized per outcome: 1) after the BCD trial, 32.0 to 69.6% of SSD patients
rejected BCD implantation, 2) the three main reasons for rejection were
experiencing limited benefit from the device, patients fearing or being unfit for
surgery and cosmetic aspects, 3) no clear prognostic factors predicting the trial
outcome could be identified. CONCLUSION: Roughly half of patients rejected BCD
implantation after a trial period. From the current literature it is unclear
which patients could benefit most from BCD implantation. High level of evidence
studies should be conducted to investigate possible prognostic factors that
predict the BCD trial outcome.
PMID- 28414694
TI - Ipsilesional Nystagmus Induced by Vibration in Subjects With Meniere's Disease or
Vestibular Schwannoma.
AB - OBJECTIVE: To analyze the frequency in which vibration-induced nystagmus (VIN)
with ipsilesional direction appears in subjects with Meniere's disease (MD) or
vestibular schwannoma (VS). STUDY DESIGN: Cross-sectional study. SETTING:
Tertiary referral center. PATIENTS: Fifty-two subjects with MD and 21 subjects
with vestibular schwannoma. INTERVENTION: Videonystagmographic recordings of VIN
at 30, 60, and 100 Hz. MAIN OUTCOME MEASURES: Direction and slow phase velocity
of VIN at 30, 60, and 100 Hz. RESULTS: Ipsilesional Nystagmus was observed in 8
of 52 subjects with MD (15.4%) and in 11 of 21 subjects affected of unilateral VS
(52.4%). Ipsilesional nystagmus was significantly higher in patients with VS (p =
0.003). The frequency of appearance of ipsilesional nystagmus in the subjects
with VS who has not been treated was significantly higher than those who
underwent radiosurgery (84.6% vs 0%, p = 0.046). CONCLUSION: Ipsilesional
vibration-induced Nystagmus can be present in subjects with vestibular deficits
caused by MD and VS.
PMID- 28414695
TI - Imaging Criteria to Predict Surgical Difficulties During Stapes Surgery.
AB - BACKGROUND AND PURPOSE: Stapes surgery for otosclerosis can be challenging if
access to the oval window niche is restricted. The aim of this study was to
determine the accuracy of the computed tomographic (CT) scan in the evaluation of
anatomical distances, and to analyze its reliability in predicting surgical
technical difficulties. MATERIAL AND METHODS: A total of 96 patients (101 ears)
were enrolled in a prospective study between 2012 and May 2015. During surgery,
we evaluated the distance D1 between the stapes and the facial nerve, distance D2
between the promontory and the facial nerve after ablation of the superstructure,
and the intraoperative discomfort of the surgeon. On preoperative CT scans, we
measured the width and depth of the oval window niche, and the angle formed by
two axes starting from the center-point of the footplate, the first tangential to
the superior wall of the promontory, and the second tangential to the inferior
wall of the fallopian canal. RESULTS: Intraoperative distances D1 and D2 were
correlated with the width of the oval window and with the facial-promontory angle
measured on imaging. CT scan measurements of the facial-promontory angle and
width of the oval window were associated with the degree of discomfort of the
surgeon. The cut-off threshold for intraoperative subjective discomfort was
computed as 1.1 mm for the width of the oval window niche, with a sensibility of
71% and a specificity of 84%. CONCLUSION: Preoperative imaging analysis of the
oval window width and the facialpromontory angle can predict operative difficulty
in otosclerosis surgery.
PMID- 28414696
TI - Decrease in Pneumococcal Otitis Media Cultures With Concomitant Increased
Antibiotic Susceptibility in the Pneumococcal Conjugate Vaccines Era.
AB - OBJECTIVE: To study the change in the incidence and antibiotic susceptibility
patterns of Streptococcus pneumoniae (Spn) in cultures obtained from children
with otitis media (OM) during the pneumococcal conjugate vaccines (PCVs) era.
STUDY DESIGN: Retrospective. SETTING: Secondary medical care center. PATIENTS:
Children less than 8 years who presented with OM and had positive pneumococcal
cultures during January 1, 2007 to December 12, 2014 were identified. Data
recorded included demographics, preadmission antibiotics, culture source, and
antibiotic susceptibility tests. We compared the pre-PCV years (2007-2008) with
the transition years (2009-2011) and the post-PCV13 years (2012-2014).
INTERVENTIONS: PCV7 (2009), PCV13 (2010), therapeutic. MAIN OUTCOME MEASURE(S):
Annual rate of Spn cultures, antibiotic susceptibility patterns. RESULTS: We
identified 134 children (76 boys, 57%) who contributed 162 pneumococcal cultures.
There was a downward trend in the annual incidence rate of Spn cultures between
the pre-PCV years, transition years, and post-PCV13 years: 11.12, 8.48, and
4.11/1000 hospitalized children/year, respectively (p = 0.08, p = 0.04). Had
there been no interventions, and based on the 2007 to 2009 average, the observed
over the expected Spn cultures ratio rates for 2010 to 2014 were 0.59, 0.45,
0.40, 0.40, and 0.25, respectively. In parallel, the susceptibility of Spn
strains to four commonly tested antibiotics significantly increased from the pre
PCV years to the transition years and the post-PCV13 years. In each period, Spn
strains were penicillin sensitive in 37, 51, and 100%; for erythromycin, 46, 71,
and 82%; for trimethoprim/sulfamethoxazole, 32, 71, and 97%; and for ceftriaxone,
95, 96, and 100%, respectively. CONCLUSION: The introduction of PCVs
significantly decreased the incidence rate of pneumococcal OM, and increased Spn
susceptibility to common antibiotics.
PMID- 28414697
TI - Feasibility of Transvesical Robotic VVF Repair in Porcine Model.
AB - Extraperitoneal transvesicoscopic vesicovaginal fistula (VVF) repair has received
limited use because of its narrow working space, longer operation time, and
technical difficulty. The present study describes the feasibility of robotic
assisted transvesicoscopic VVF repair in an animal model. Two Yorkshire swine
underwent robotic-assisted laparoscopic (RAL) VVF repair. With the 4 trocars, an
artificial VVF was made in the supratrigonal area and VVF repair was performed in
3 layers as in open VVF repair methods. The mean operation time was 108 minutes.
The operation time was prolonged in 1 case due to weak fixation of bladder to
anterior abdominal wall. Equipment interference did not occur. Tissue
manipulation and suturing were easy. The results of this study suggest that
extraperitoneal RAL procedures for VVF repair may be an effective minimally
invasive modality with reduced morbidity. A shorter operation time and easy
suturing technique were the distinct merits of the extraperitoneal RAL technique.
PMID- 28414698
TI - The Feasibility of Thoracoscopic Resection in Bronchiectasis.
AB - INTRODUCTION: Minimally invasive surgery is the treatment of choice in early
stage lung cancer. However, experience in infectious lung disease, primarily
bronchiectasis, is limited probably because of the presence of dense pleural
adhesions, multiple lymph nodes, and spiral bronchial arteries. The present study
shows our experience of video-assisted thoracoscopic surgery (VATS) lobectomy and
segmentectomy in the treatment of bronchiectasis. MATERIALS AND METHODS: Patients
who underwent VATS lobectomy or segmentectomy in our clinic between April 2008
and 2015 were retrospectively evaluated. Surgery was indicated in patients with
radiologic localized bronchiectasis who also had a history of recurrent lower
respiratory tract infection or expectorating mucopurulent secretion. The patients
were analyzed in terms of age, sex, thoracotomy conversion rate, postoperative
drainage amount, chest tube removal time, length of hospital stay, morbidity, and
mortality. RESULTS: A total of 44 patients initially underwent VATS pulmonary
anatomic resection and 41 procedures were completed on 40 patients. One patient
had bilateral resection. Fifteen patients were male individuals and 26 were
female individuals. The average age was 31.4 (15 to 57) years. Forty lobectomies
and 1 segmentectomy were performed. The conversion rate was 6.8%. VATS was
performed on 28 patients by 3 ports, 8 patients by 2 ports, and 5 patients by a
single port. In terms of anatomic resections, 18 patients underwent left lower
lobectomy, 8 right lower lobectomy, 8 middle lobectomy, 6 right upper lobectomy,
and 1 patient underwent lingular segmentectomy. No major postoperative
complication or mortality was observed. Prolonged air leak was observed in 2
patients and subcutaneous emphysema occurred in 2 patients. The average
postoperative drainage amount, chest tube removal time, and length of hospital
stay were 320 mL, 3.1 (1 to 11) days, and 4.6 (2 to 11) days, respectively.
CONCLUSIONS: VATS pulmonary resection is a safe, feasible, and effective
treatment in the surgery of bronchiectasis with low morbidity and mortality
rates. Moreover, because of cosmetic results, patients with benign diseases such
as bronchiectasis could be initiated by minimally invasive surgery options just
like patients with malignancies.
PMID- 28414699
TI - Etiology of Leaks Following Sleeve Gastrectomy: Current Evidence.
AB - PURPOSE: The purpose of this paper is to study the causes of leaks following
sleeve gastrectomy (SG). MATERIALS AND METHODS: Pubmed was searched during
January 2016 for publications reporting leak after SG. A total of 205
publications were identified, of which 17 papers were selected. RESULTS: In about
3018 patients, reinforcement was used compared with 4595 patients, in whom no
reinforcement was applied; both groups were representing matched bariatric
populations. The use of reinforcement/buttressing has resulted in different rates
of leaks ranging from 0% to 3.9%; whereas with no reinforcement/buttressing, the
leak rate was 0.16% to 3.5%. The use of reinforcement/buttressing did not result
in reduction of leak to a statistical significance although the trend was
suggesting so (P=0.06), whereas no reinforcement/buttressing did not
statistically increase the leak rate (P=0.10). CONCLUSIONS: No statistical
significant difference of leak with or without reinforcement. This mean case
complexity and surgical technique and experience are the sole factors for leaks
following SG.
PMID- 28414700
TI - Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in
Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic
Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.
AB - This randomized trial investigated whether a 2-dose administration of intravenous
ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective
than a single-dose administration in preventing postoperative nausea and vomiting
(PONV) in 89 patients who were scheduled to undergo laparoscopic operation for
benign gynecologic diseases and to receive intravenous patient-controlled
analgesia for relief of postoperative pain. After assignment at a ratio of 1:1,
intravenous ramosetron (0.3 mg) was initially administered at the end of skin
closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were
administered to the study and control groups, respectively, at 4 hours after the
operation. The baseline and operative characteristics were similar between the
groups. The incidence of PONV during the 24-hour period after operation which was
assessed as the primary endpoint did not differ between the groups. No serious
adverse events occurred in either group. A 2-dose administration of intravenous
ramosetron may not be superior to a single-dose administration in preventing PONV
in patients undergoing laparoscopic operation for benign gynecologic diseases.
PMID- 28414701
TI - Complications of Minimally Invasive Surgery in Children: A Prospective Morbidity
and Mortality Analysis Using the Clavien-Dindo Classification.
AB - There is a lack of information about evaluation of pediatric minimal access
surgery complications; the Clavien-Dindo classification was never used for a
large series of laparoscopic and thoracoscopic pediatric procedures. With a
prospective Morbidity and Mortality database, all the minimal access surgical
procedures carried out between 2012 and 2016 were included in this study.
Statistical analyses were used to valuate modification of surgical techniques in
to 2 periods (period 1: January 2012 to February 2014; period 2: February 2014 to
February 2016). A total of 1374 minimal access procedures were performed on 1371
patients. The overall complication rate was 2.9%. No differences, in terms of
complications, were observed between elective and emergency procedures (P=0.3).
There was a significant difference between the complication rate of thoracoscopic
surgery (P=0.027). These results provide the relevance of adequate recording
system and standardized classification for analyses and reduction of
complications for pediatric minimal access procedures.
PMID- 28414702
TI - Minimally Invasive Treatment for Appendiceal Mass Formed After Acute Perforated
Appendicitis.
AB - The optimal treatment for appendiceal mass formed after appendiceal rupture due
to acute appendicitis is surrounded with controversy. The treatment strategy
ranges from open surgery (emergency or interval appendectomy), laparoscopic
appendectomy, and image-guided drainage, to conservative treatment with or
without antibiotics. Nonsurgical treatment (including conservative and drainage
treatment), followed by interval appendectomy to prevent recurrence, is the
traditional management of these patients. The need for interval appendectomy
after a successful conservative or/and image-guided drainage treatment, has
recently been questioned as the risk of recurrence is relatively small. Several
authors consider that even in cases involving only ambulatory follow-up
observation, without interval surgery after conservative management, the
recurrence rate and risks of missing underlying pathologies were not high. This
article evaluates the minimally invasive treatment modalities in the management
of appendiceal mass, risk of undetected serious disease, and the need for
interval appendectomy to prevent recurrence.
PMID- 28414704
TI - An updated view on the reliability of different protocols for the assessment of
conditioned pain modulation.
PMID- 28414703
TI - Recruitment, Methods, and Descriptive Results of a Physiologic Assessment of
Latino Farmworkers: The California Heat Illness Prevention Study.
AB - OBJECTIVE: The California heat illness prevention study (CHIPS) devised
methodology and collected physiological data to assess heat related illness (HRI)
risk in Latino farmworkers. METHODS: Bilingual researchers monitored HRI across a
workshift, recording core temperature, work rate (metabolic equivalents [METs]),
and heart rate at minute intervals. Hydration status was assessed by changes in
weight and blood osmolality. Personal data loggers and a weather station measured
exposure to heat. Interviewer administered questionnaires were used to collect
demographic and occupational information. RESULTS: California farmworkers (n =
588) were assessed. Acceptable quality data was obtained from 80% of participants
(core temperature) to 100% of participants (weight change). Workers (8.3%)
experienced a core body temperature more than or equal to 38.5 degrees C and
11.8% experienced dehydration (lost more than 1.5% of body weight). CONCLUSIONS:
Methodology is presented for the first comprehensive physiological assessment of
HRI risk in California farmworkers.
PMID- 28414706
TI - Reply.
PMID- 28414705
TI - Small fiber neuropathy or small fiber pathology?
PMID- 28414707
TI - Supporting the updated definition of pain. But what about labour pain?
PMID- 28414708
TI - Reply.
PMID- 28414709
TI - Robotic Surgery: Fast Forward to Telemedicine.
AB - Since the realization that certain maladies can be corrected via surgical
techniques, we have been consumed by the desire to constantly advance the tools
of surgery, as well as the techniques. In recent times, computer-assisted
surgical tools have emerged and are growing in their use. The Puma 560 emerged in
1985 for brain biopsies and laparoscopic surgery. Prostatic surgery was performed
by the Probot in 1988. In 1992, fittings in the femur were placed using the
ROBODOC. These early robotic endeavors gave rise to AESOP, ZEUS and the
relatively intuitive da Vinci(r) Surgical System. These advances reflect the
rapid growth of knowledge in the technology sector. These ever increasingly
complex robotic-driven procedures are favored because this surgery provides a
less invasive and therefore more tolerable "surgical" procedure for patients. In
turn, these less invasive experiences may also allow for faster recovery times,
reducing hospital stays and potentially costs. Importantly, this technology is
accompanied by the development of more targeted surgical interventions. On the
negative side, these technologies are initially expensive. However, as is always
the case, there is hope that future devices will be more economical as more
institutions invest. Another trend which may reduce costs is in the design of the
robotic devices to incorporate a common central core of technology, to which
other sub-devices can be attached, offering additional cost savings while
enhancing flexibility.
PMID- 28414710
TI - Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid
thioesters.
AB - Biotin is an essential vitamin in plants and mammals, functioning as the carbon
dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA
synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring
the integrity of the carbon chain in biotin synthesis. BioW catalyzes the
condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP
dependent manner to form pimeloyl-CoA, the first dedicated biotin building block.
Multiple structures of Bacillus subtilis BioW together capture all three
substrates, as well as the intermediate pimeloyl-adenylate and product
pyrophosphate (PPi), indicating that the enzyme uses an internal ruler to select
the correct dicarboxylic acid substrate. Both the catalytic mechanism and the
surprising stability of the adenylate intermediate were rationalized through site
directed mutagenesis. Building on this understanding, BioW was engineered to
synthesize high-value heptanoyl (C7) and octanoyl (C8) monocarboxylic acid-CoA
and C8 dicarboxylic-CoA products, highlighting the enzyme's synthetic potential.
PMID- 28414711
TI - The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming
enzymes.
AB - Reactions that activate carboxylates through acyl-adenylate intermediates are
found throughout biology and include acyl- and aryl-CoA synthetases and tRNA
synthetases. Here we describe the characterization of Aquifex aeolicus BioW,
which represents a new protein fold within the superfamily of adenylating
enzymes. Substrate-bound structures identified the enzyme active site and
elucidated the mechanistic strategy for conjugating CoA to the seven-carbon
alpha,omega-dicarboxylate pimelate, a biotin precursor. Proper position of
reactive groups for the two half-reactions is achieved solely through movements
of active site residues, as confirmed by site-directed mutational analysis. The
ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent
of pre-transfer proofreading observed in some tRNA synthetases, and we show that
this activity can be abolished by mutation of a single residue. These studies
illustrate how BioW can carry out three different biologically prevalent chemical
reactions (adenylation, thioesterification, and proofreading) in the context of a
new protein fold.
PMID- 28414712
TI - The need for a worldwide consensus for cell line authentication: Experience
implementing a mandatory requirement at the International Journal of Cancer.
AB - Cell lines are used in life science research worldwide as biological surrogates.
All cell lines are subject to major limitations when used as research tools,
including (i) cross-contamination with other cells cultured in the same
laboratory environment and (ii) evolution in vitro that renders a given cell line
inappropriate as a surrogate for a specific biological hypothesis. There is ample
evidence that cross-contamination or phenotypic drift of cells in culture can
generate irreproducible or misleading data. A small number of scientific journals
the International Journal of Cancer being at the forefront-and funding agencies
have recently moved forward to ask for obligatory cell line authentication data.
The history of implementing such rules by the International Journal of Cancer
exemplifies the difficulties encountered when installing mandatory quality
measures in life sciences.
PMID- 28414713
TI - Less fear, more diversity.
AB - Fear is an instinctual response that's adaptive and critical for survival when it
is short-lived but can lead to anxiety disorders when chronic. Studying how the
brain controls our fears helps us understand the mechanisms required to recover
from traumatic experiences and what goes wrong when we don't. Research in rodents
has identified neural circuits and molecular mechanisms regulating fear
expression. Rodent work has been amenable to translation to humans and has led to
improvements in clinical therapies for anxiety disorders. The societal benefit of
this type of research is magnified when performed in minority-serving
institutions, offering high-caliber training opportunities to increase ethnic
diversity in science.
PMID- 28414714
TI - Excess atherosclerosis in systemic lupus erythematosus,-A matter of renal
involvement: Case control study of 281 SLE patients and 281 individually matched
population controls.
AB - BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which
predominantly affects young females (90%). SLE is associated with a shorter life
expectancy than in the general population. Standardized mortality ratios (SMR) of
2.4 have been reported, which is comparable to diabetes. In modern societies
cardiovascular disease (CVD) is the major cause of premature mortality.
Accelerated atherosclerosis is generally assumed to be the underlying cause for
SLE related CVD. However, previous studies diverge regarding whether
atherosclerosis is more common in SLE than in controls. With this in mind and
based on own clinical experience we hypothesized that accelerated atherosclerosis
is not a general feature of SLE, but prevails in SLE subgroups. METHODS: 281 SLE
patients and 281 individually age and sex matched population controls, were
investigated clinically. Fasting blood samples and risk factor data were
collected. All participants were subject to B-mode ultrasonography of the carotid
arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were
recorded. Two SLE subgroups previously described to be at high CVD risk; 1)
patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL),
and one subgroup reported to be at comparatively lower CVD risk; patients
positive for Sjogren's syndrome antigens A/B (SSA/SSB) antibodies were analyzed
separately in comparison with their respective matched controls. RESULTS: Median
age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart,
cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%,
p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients
had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age
adjustment plaques, but not mIMT, remained associated with previous CVD events.
Therefore we focused further analyses on plaques, a more robust measure of
atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB
(40%) positive patients, had more plaques than their respective controls (23% vs.
11%, p = 0.008). Notably, patients with nephritis were younger than other SLE
patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we
performed an age-matched nested case-control analysis, which demonstrated that
patients with nephritis had twice as often plaques (23%) as both non-nephritis
patients (11%, p = 0.038) and controls (12%, p = 0.035). CONCLUSIONS: In SLE
excess carotid plaques are essentially confined to the SLE subgroup with
nephritis. This subgroup had plaques twice as often as age-matched non-nephritis
SLE patients and population controls. Non-nephritis SLE patients, including the
aPL positive subgroup, which has a high CVD risk, had similar prevalence of
plaques as controls. To prevent later CVD events, this novel observation calls
for risk factor screening and initiation of anti-atherosclerotic treatment
selectively in SLE nephritis patients. Preferably at nephritis onset, which is
often at a young age. In a general perspective this study demonstrates the
importance to perform careful clinical subgroup analyses when investigating
heterogeneous, hitherto not clearly defined, conditions like SLE.
PMID- 28414716
TI - Dynamics of adaptive immunity against phage in bacterial populations.
AB - The CRISPR (clustered regularly interspaced short palindromic repeats) mechanism
allows bacteria to adaptively defend against phages by acquiring short genomic
sequences (spacers) that target specific sequences in the viral genome. We
propose a population dynamical model where immunity can be both acquired and
lost. The model predicts regimes where bacterial and phage populations can co
exist, others where the populations exhibit damped oscillations, and still others
where one population is driven to extinction. Our model considers two key
parameters: (1) ease of acquisition and (2) spacer effectiveness in conferring
immunity. Analytical calculations and numerical simulations show that if spacers
differ mainly in ease of acquisition, or if the probability of acquiring them is
sufficiently high, bacteria develop a diverse population of spacers. On the other
hand, if spacers differ mainly in their effectiveness, their final distribution
will be highly peaked, akin to a "winner-take-all" scenario, leading to a
specialized spacer distribution. Bacteria can interpolate between these limiting
behaviors by actively tuning their overall acquisition probability.
PMID- 28414715
TI - Transcriptional regulatory logic of the diurnal cycle in the mouse liver.
AB - Many organisms exhibit temporal rhythms in gene expression that propel diurnal
cycles in physiology. In the liver of mammals, these rhythms are controlled by
transcription-translation feedback loops of the core circadian clock and by
feeding-fasting cycles. To better understand the regulatory interplay between the
circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites
(DHSs) in the mouse liver during a diurnal cycle. The intensity of DNase I
cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs
harbor regulatory elements that control rhythmic transcription. Using chromatin
immunoprecipitation followed by DNA sequencing (ChIP-seq), we found that
hypersensitivity cycled in phase with RNA polymerase II (Pol II) loading and
H3K27ac histone marks. We then combined the DHSs with temporal Pol II profiles in
wild-type (WT) and Bmal1-/- livers to computationally identify transcription
factors through which the core clock and feeding-fasting cycles control diurnal
rhythms in transcription. While a similar number of mRNAs accumulated
rhythmically in Bmal1-/- compared to WT livers, the amplitudes in Bmal1-/- were
generally lower. The residual rhythms in Bmal1-/- reflected transcriptional
regulators mediating feeding-fasting responses as well as responses to rhythmic
systemic signals. Finally, the analysis of DNase I cuts at nucleotide resolution
showed dynamically changing footprints consistent with dynamic binding of
CLOCK:BMAL1 complexes. Structural modeling suggested that these footprints are
driven by a transient heterotetramer binding configuration at peak activity.
Together, our temporal DNase I mappings allowed us to decipher the global
regulation of diurnal transcription rhythms in the mouse liver.
PMID- 28414717
TI - A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent
bulk endocytosis.
AB - Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis
(ADBE) are two predominant forms of synaptic vesicle (SV) endocytosis, elicited
by moderate and strong stimuli, respectively. They are tightly coupled with
exocytosis for sustained neurotransmission. However, the underlying mechanisms
are ill defined. We previously reported that the Flower (Fwe) Ca2+ channel
present in SVs is incorporated into the periactive zone upon SV fusion, where it
triggers CME, thus coupling exocytosis to CME. Here, we show that Fwe also
promotes ADBE. Intriguingly, the effects of Fwe on CME and ADBE depend on the
strength of the stimulus. Upon mild stimulation, Fwe controls CME independently
of Ca2+ channeling. However, upon strong stimulation, Fwe triggers a Ca2+ influx
that initiates ADBE. Moreover, knockout of rodent fwe in cultured rat hippocampal
neurons impairs but does not completely abolish CME, similar to the loss of
Drosophila fwe at the neuromuscular junction, suggesting that Fwe plays a
regulatory role in regulating CME across species. In addition, the function of
Fwe in ADBE is conserved at mammalian central synapses. Hence, Fwe exerts
different effects in response to different stimulus strengths to control two
major modes of endocytosis.
PMID- 28414718
TI - Achieving global perfect homeostasis through transporter regulation.
AB - Nutrient homeostasis-the maintenance of relatively constant internal nutrient
concentrations in fluctuating external environments-is essential to the survival
of most organisms. Transcriptional regulation of plasma membrane transporters by
internal nutrient concentrations is typically assumed to be the main mechanism by
which homeostasis is achieved. While this mechanism is homeostatic we show that
it does not achieve global perfect homeostasis-a condition where internal
nutrient concentrations are completely independent of external nutrient
concentrations for all external nutrient concentrations. We show that the
criterion for global perfect homeostasis is that transporter levels must be
inversely proportional to net nutrient flux into the cell and that downregulation
of active transporters (activity-dependent regulation) is a simple and
biologically plausible mechanism that meets this criterion. Activity-dependent
transporter regulation creates a trade-off between robustness and efficiency,
i.e., the system's ability to withstand perturbation in external nutrients and
the transporter production rate needed to maintain homeostasis. Additionally, we
show that a system that utilizes both activity-dependent transporter
downregulation and regulation of transporter synthesis by internal nutrient
levels can create a system that mitigates the shortcomings of each of the
individual mechanisms. This analysis highlights the utility of activity-dependent
regulation in achieving homeostasis and calls for a re-examination of the
mechanisms of regulation of other homeostatic systems.
PMID- 28414719
TI - Crucial role of estrogen for the mammalian female in regulating semen coagulation
and liquefaction in vivo.
AB - Semen liquefaction changes semen from a gel-like to watery consistency and is
required for sperm to gain mobility and swim to the fertilization site in the
Fallopian tubes. Kallikrein-related peptidases 3 (KLK3) and other kallikrein
related peptidases from male prostate glands are responsible for semen
liquefaction by cleaving gel-forming proteins (semenogelin and collagen). In a
physiological context, the liquefaction process occurs within the female
reproductive tract. How seminal proteins interact with the female reproductive
environment is still largely unexplored. We previously reported that conditional
genetic ablation of Esr1 (estrogen receptor alpha) in the epithelial cells of the
female reproductive tract (Wnt7aCre/+;Esr1f/f) causes female infertility, partly
due to a drastic reduction in the number of motile sperm entering the oviduct. In
this study, we found that post-ejaculated semen from fertile wild-type males was
solidified and the sperm were entrapped in Wnt7aCre/+;Esr1f/f uteri, compared to
the watery semen (liquefied) found in Esr1f/f controls. In addition, semenogelin
and collagen were not degraded in Wnt7aCre/+;Esr1f/f uteri. Amongst multiple gene
families aberrantly expressed in the absence of epithelial ESR1, we have
identified that a lack of Klks in the uterus is a potential cause for the
liquefaction defect. Pharmacological inhibition of KLKs in the uterus replicated
the phenotype observed in Wnt7aCre/+;Esr1f/f uteri, suggesting that loss of
uterine and seminal KLK function causes this liquefaction defect. In human
cervical cell culture, expression of several KLKs and their inhibitors (SPINKs)
was regulated by estrogen in an ESR1-dependent manner. Our study demonstrates
that estrogen/ESR1 signaling in the female reproductive tract plays an
indispensable role in normal semen liquefaction, providing fundamental evidence
that exposure of post-ejaculated semen to the suboptimal microenvironment in the
female reproductive tract leads to faulty liquefaction and subsequently causes a
fertility defect.
PMID- 28414720
TI - Land altitude, slope, and coverage as risk factors for Porcine Reproductive and
Respiratory Syndrome (PRRS) outbreaks in the United States.
AB - Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most
impactful disease on the North American swine industry. The Swine Health
Monitoring Project (SHMP) is a national volunteer initiative aimed at monitoring
incidence and, ultimately, supporting swine disease control, including PRRS. Data
collected through the SHMP currently represents approximately 42% of the sow
population of the United States. The objective of the study here was to
investigate the association between geographical factors (including land
elevation, and land coverage) and PRRS incidence as recorded in the SHMP. Weekly
PRRS status data from sites participating in the SHMP from 2009 to 2016 (n = 706)
was assessed. Number of PRRS outbreaks, years of participation in the SHMP, and
site location were collected from the SHMP database. Environmental features
hypothesized to influence PRRS risk included land coverage (cultivated areas,
shrubs and trees), land altitude (in meters above sea level) and land slope (in
degrees compared to surrounding areas). Other risk factors considered included
region, production system to which the site belonged, herd size, and swine
density in the area in which the site was located. Land-related variables and pig
density were captured in raster format from a number of sources and extracted to
points (farm locations). A mixed-effects Poisson regression model was built; and
dependence among sites that belonged to a given production system was accounted
for using a random effect at the system level. The annual mean and median number
of outbreaks per farm was 1.38 (SD: 1.6), and 1 (IQR: 2.0), respectively. The
maximum annual number of outbreaks per farm was 9, and approximately 40% of the
farms did not report any outbreak. Results from the final multivariable model
suggested that increments of swine density and herd size increased the risk for
PRRS outbreaks (P < 0.01). Even though altitude (meters above sea level) was not
significant in the final model, farms located in terrains with a slope of 9% or
higher had lower rates of PRRS outbreaks compared to farms located in terrains
with slopes lower than 2% (P < 0.01). Finally, being located in an area of
shrubs/ herbaceous cover and trees lowered the incidence rate of PRRS outbreaks
compared to being located in cultivated/ managed areas (P < 0.05). In conclusion,
highly inclined terrains were associated with fewer PRRS outbreaks in US sow
farms, as was the presence of shrubs and trees when compared to cultivated/
managed areas. Influence of terrain characteristics on spread of airborne
diseases, such as PRRS, may help to predicting disease risk, and effective
planning of measures intended to mitigate and prevent risk of infection.
PMID- 28414721
TI - A novel smart navigation system for intramedullary nailing in orthopedic surgery.
AB - This paper proposes a novel smart surgical navigation system for intramedullary
nailing in orthopedic surgery. Using a handle-integrated laser guidance module,
the system can target a drill insertion point onto skin, indicating an accurate
target position to perpendicularly access an invisible distal hole. The proposed
handle-integration-based fixation of the laser guidance module precisely defines
the relative position of the module with respect to the distal hole.
Consequently, unlike conventional systems, the proposed system can indicate the
target insertion point without any help from bulky and costly external position
tracking equipment that is usually required for compensating disturbances
generated by external impacts. After insertion, a correct drilling direction
toward the distal hole is guided by real-time drilling angle measurement modules
one integrated with the nail handle and the other with the drill body. Each
module contains a 9-axis inertial sensor and a Bluetooth communication device.
These two modules work together to provide real-time drilling angle data,
allowing calculation of the directional error toward the center of the distal
hole in real time. The proposed system removes the need for fluoroscopy and
provides a compact and cost-effective solution compared with conventional
systems.
PMID- 28414722
TI - Re-visiting the tympanic membrane vicinity as core body temperature measurement
site.
AB - Core body temperature (CBT) is an important and commonly used indicator of human
health and endurance performance. A rise in baseline CBT can be attributed to an
onset of flu, infection or even thermoregulatory failure when it becomes
excessive. Sites which have been used for measurement of CBT include the
pulmonary artery, the esophagus, the rectum and the tympanic membrane. Among
them, the tympanic membrane is an attractive measurement site for CBT due to its
unobtrusive nature and ease of measurement facilitated, especially when
continuous CBT measurements are needed for monitoring such as during military,
occupational and sporting settings. However, to-date, there are still polarizing
views on the suitability of tympanic membrane as a CBT site. This paper will
revisit a number of key unresolved issues in the literature and also presents,
for the first time, a benchmark of the middle ear temperature against temperature
measurements from other sites. Results from experiments carried out on human and
primate subjects will be presented to draw a fresh set of insights against the
backdrop of hypotheses and controversies.
PMID- 28414723
TI - Prevalence and determinants of stereotypic behaviours and physiological stress
among tigers and leopards in Indian zoos.
AB - India's charismatic wildlife species are facing immense pressure from
anthropogenic-induced environmental perturbations. Zoos play a major role in the
conservation of threatened species, but their adaptation in captivity is posing a
major challenge globally. Stress from inadequate adaptation could lead to
suppression of cognitive functioning and increased display of stereotypic
behaviour. It is thus necessary to measure biological traits like behaviour,
stress physiology, and contextual factors driving the animals maintained at zoos.
In this study, we assessed stereotypic behaviour and stress physiology employing
standard behaviour scoring, non-invasive stress monitoring, and their contextual
drivers in a sub-population of two large felid species managed in six Indian
zoos. The prevalence and intensity of stereotypic behaviours and levels of faecal
corticosterone metabolites (FCM) were ascertained among 41 Royal Bengal tigers
Panthera tigris tigris and 21 Indian leopards Panthera pardus fusca between April
2014 and March 2015. Behavioural observations showed that tigers spent more time
stereotyping (12%) than leopards (7%) during daylight hours. Stress levels
assessed using FCM revealed that tigers (23.6 +/- 1.62 ng/g) had marginally lower
level of corticosterone metabolites than leopards (27.2 +/-1.36 ng/g).
Stereotypic behaviour increased significantly with FCM level when the effect of
heath status was controlled in tigers, and the effects tree cover, stone, den and
keeper attitude controlled in leopards. Comparison of stereotypes of tigers with
various biological and environmental factors using binary logistic regression
revealed that stereotypic prevalence decreased with increased enclosure size, and
enclosure enrichments like presence of pools and stones, when managed socially
with conspecifics, and with positive keeper attitude, these factors accounting
for 43% of variations in stereotypic prevalence among tigers. Stereotype among
leopards was significantly absent when associated with increased tree cover and
presence of pool, and den in the enclosure, age and among zoo-born than wild-born
ones. These factors explain 81% of variations in stereotypic prevalence in them.
A comparison of FCM levels with context-dependent factors revealed that stress
levels among tigers decreased significantly with enclosure size and with
individuals from nil to low, and severity of health issues. These factors explain
64% of variations in FCM levels. In leopards, the presence of stones in the
enclosure and keepers with positive attitude resulted in significant decrease in
FCM levels, these factors together accounting for 94% of variations. Multiple
regressions on selected variables based on Factor Analysis of Mixed Data showed
that in tigers the intensity of stereotype decreased significantly with enclosure
size, sociality and positive keeper attitude and FCM level with health problems.
Similarly, analyses in leopards revealed that intensity of stereotype decreased
significantly with tree cover, age and FCM level with positive keeper attitude.
Overall, our study suggests that to reduce stereotypes and stress level, tigers
in captivity should be managed in larger enclosures enriched with pool, and
stones, and in appropriate social conditions with adequate veterinary care.
Leopards should be managed in enclosures with dense tree cover, pool, stones and
den. Positive keeper attitude plays a crucial role in the welfare of both the
species in captivity. Our study is promising and is comparable with their natural
behaviour in the wild; for example, tigers require larger natural habitats, while
leopards can manage even with smaller isolated patches but with dense vegetation
cover.
PMID- 28414724
TI - Serine protease Bm-SP142 was differentially expressed in resistant and
susceptible Bombyx mori strains, involving in the defence response to viral
infection.
AB - Bm-SP142 is a 35 kDa protease in the silkworm, but its exact functions remain
unknown. In this study, sequence alignment revealed that the His-Asp-Ser
catalytic triad is embedded in the TAAHC-DIAL-GDSGGP sequence motif, establishing
Bm-SP142 as a serine protease. Soluble recombinant GST-BmSP142 was expressed and
purified, and serine protease activity was confirmed in vitro. RT-qPCR results
indicated that Bm-SP142 was mainly expressed in the middle part of the silkworm
midgut, and Bm-SP142 transcripts were significantly up-regulated at 24 hours post
infection (hpi) in BmBDV-resistant strains (798) inoculated with BmBDV and BmNPV
resistant strains (NB) inoculated with BmNPV, but not in BmBDV-susceptible
strains (306). Surprisingly, transcripts were significantly down-regulated at 12
hpi in BmNPV-susceptible strains (HuaBa 35) inoculated with BmNPV, compared with
healthy silkworms. Recombinant BmNPV treated with purified Bm-SP142 effectively
impaired its ability to infect BmN cells, and Bm-SP142 decreases the efficiency
of BmNPV and BmBDV propagation in silkworms. Furthermore, overexpression of Bm
SP142 in BmN cells inhibited viral propagation.
PMID- 28414725
TI - Evolution of EBV seroprevalence and primary infection age in a French hospital
and a city laboratory network, 2000-2016.
AB - BACKGROUND: According to rare studies, the age at EBV primary infection (PI) has
recently risen in some developed countries. A later age at infection is generally
considered a risk factor for severe EBV PI, although few studies exist on this
subject. Our investigation aimed to determine whether EBV seroprevalence and EBV
PI epidemiology have evolved in France, and to what extent age and infection
intensity (regarding biological parameters) are correlated. METHODS AND FINDINGS:
We conducted a retrospective study of the following EBV serological tests
databases: tests carried out at Grenoble University Hospital (2000-2016) (n =
53,553); and tests carried out by a network of city laboratories in Grenoble area
(2008-2015) (n = 27,485). The hospital population showed a continuous,
significant decrease in EBV seroprevalence over the studied period for patients
aged 20 and over (p<0.01). The seroprevalence also decreased for different age
classes (<10, 15-19, 20-30, and 30-40 years old) over the periods 2001-2005, 2006
2010, and 2011-2015. Consistently, the age at PI was significantly higher in the
years 2008-2015 than in the years 2001-2007 (15.6+/-12.0 vs. 13.7+/-11.0; p =
0.03). The city laboratory population showed the same trend of decreasing
seroprevalence (p = 0.06); no significant variations in age at PI were observed.
The age at PI was positively correlated with ASAT, ALAT, gammaGT, and bilirubin
blood levels (p<0.01) and negatively correlated with platelet counts (p<0.05).
CONCLUSION: In the last 15 years, the age at EBV PI has increased, whereas
seroprevalence has decreased. Moreover, our findings confirm the positive
correlation between age and biological abnormalities. Taken together, these
results suggest that the incidence of severe EBV PI will increase in the future.
PMID- 28414727
TI - Trypanosoma brucei TbIF1 inhibits the essential F1-ATPase in the infectious form
of the parasite.
AB - The mitochondrial (mt) FoF1-ATP synthase of the digenetic parasite, Trypanosoma
brucei, generates ATP during the insect procyclic form (PF), but becomes a
perpetual consumer of ATP in the mammalian bloodstream form (BF), which lacks a
canonical respiratory chain. This unconventional dependence on FoF1-ATPase is
required to maintain the essential mt membrane potential (Deltapsim). Normally,
ATP hydrolysis by this rotary molecular motor is restricted to when eukaryotic
cells experience sporadic hypoxic conditions, during which this compulsory
function quickly depletes the cellular ATP pool. To protect against this cellular
treason, the highly conserved inhibitory factor 1 (IF1) binds the enzyme in a
manner that solely inhibits the hydrolytic activity. Intriguingly, we were able
to identify the IF1 homolog in T. brucei (TbIF1), but determined that its
expression in the mitochondrion is tightly regulated throughout the life cycle as
it is only detected in PF cells. TbIF1 appears to primarily function as an
emergency brake in PF cells, where it prevented the restoration of the Deltapsim
by FoF1-ATPase when respiration was chemically inhibited. In vitro, TbIF1
overexpression specifically inhibits the hydrolytic activity but not the
synthetic capability of the FoF1-ATP synthase in PF mitochondria. Furthermore,
low MUM amounts of recombinant TbIF1 achieve the same inhibition of total mt
ATPase activity as the FoF1-ATPase specific inhibitors, azide and oligomycin.
Therefore, even minimal ectopic expression of TbIF1 in BF cells proved lethal as
the indispensable Deltapsim collapsed due to inhibited FoF1-ATPase. In summary,
we provide evidence that T. brucei harbors a natural and potent unidirectional
inhibitor of the vital FoF1-ATPase activity that can be exploited for future
structure-based drug design.
PMID- 28414726
TI - Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by
differentially regulating cytotoxic T and myeloid-derived suppressor cells.
AB - Post-surgical tumor recurrence is a common problem in cancer treatment. In the
present study, the role of neem leaf glycoprotein (NLGP), a novel
immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was
examined. Data suggest that NLGP prevents tumor recurrence after surgical removal
of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP
treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased
population of suppressor cells, especially myeloid-derived suppressor cells
(MDSCs) was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity
towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture
caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate
the role of CD8+ T cells, specifically in association with the downregulation in
MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically
tumor removed mice and tumor recurrence was noted. These mice also exhibited
increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased
cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T
cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects
of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor
hosts is maintained to eliminate the residual tumor mass appearing during
recurrence.
PMID- 28414728
TI - Clown-care reduces pain in children with cerebral palsy undergoing recurrent
botulinum toxin injections- A quasi-randomized controlled crossover study.
AB - OBJECTIVE: We investigated the impact of clown-care on pain in 45 children with
cerebral palsy who underwent recurrent Botulinum-toxin injections (age 7.04+/-
4.68 years). Participants were randomized to receive either clown (n = 20) or
standard (n = 25) -care. METHODS: Pain Visual-Analogue-Scale (range 1-5) was
reported before and after procedures. Pain assessment was lower for children
undergoing Botulinum-toxin injections with clown-care (2.89+/- 1.36) compared to
standard-care (3.85+/- 1.39; p = 0.036) even though pain anticipated prior to
procedures was similar (~3). FINDINGS: Children who underwent the first procedure
with clown-care reported lower pain even after they crossed-over to the following
procedure which was standard (p = 0.048). Carryover effect was more prominent in
injection-naive children (p = 0.019) and during multiple procedures (p = 0.009).
Prior pain experience correlated with pain in subsequent procedures only when
first experience was standard-care (p = 0.001). CONCLUSIONS: Clown-care
alleviated pain sensation during Botulinum-toxin injections and initial clown
care experience reduced pain during subsequent injections even though clowns were
not present. TRIAL REGISTRATION: clinicaltrials.gov ID # NCT01377883.
PMID- 28414729
TI - An evaluation of mental workload with frontal EEG.
AB - Using a wireless single channel EEG device, we investigated the feasibility of
using short-term frontal EEG as a means to evaluate the dynamic changes of mental
workload. Frontal EEG signals were recorded from twenty healthy subjects
performing four cognitive and motor tasks, including arithmetic operation, finger
tapping, mental rotation and lexical decision task. Our findings revealed that
theta activity is the common EEG feature that increases with difficulty across
four tasks. Meanwhile, with a short-time analysis window, the level of mental
workload could be classified from EEG features with 65%-75% accuracy across
subjects using a SVM model. These findings suggest that frontal EEG could be used
for evaluating the dynamic changes of mental workload.
PMID- 28414730
TI - Elements including metals in the atomizer and aerosol of disposable electronic
cigarettes and electronic hookahs.
AB - OBJECTIVE: Our purpose was to quantify 36 inorganic chemical elements in aerosols
from disposable electronic cigarettes (ECs) and electronic hookahs (EHs), examine
the effect of puffing topography on elements in aerosols, and identify the source
of the elements. METHODS: Thirty-six inorganic chemical elements and their
concentrations in EC/EH aerosols were determined using inductively coupled plasma
optical emission spectroscopy, and their source was identified by analyzing
disassembled atomizers using scanning electron microscopy and energy dispersive X
ray spectroscopy. RESULTS: Of 36 elements screened, 35 were detected in EC/EH
aerosols, while only 15 were detected in conventional tobacco smoke. Some
elements/metals were present in significantly higher concentrations in EC/EH
aerosol than in cigarette smoke. Concentrations of particular elements/metals
within EC/EH brands were sometimes variable. Aerosols generated at low and high
air-flow rates produced the same pattern of elements, although the total element
concentration decreased at the higher air flow rate. The relative amount of
elements in the first and last 60 puffs was generally different. Silicon was the
dominant element in aerosols from all EC/EH brands and in cigarette smoke. The
elements appeared to come from the filament (nickel, chromium), thick wire
(copper coated with silver), brass clamp (copper, zinc), solder joints (tin,
lead), and wick and sheath (silicon, oxygen, calcium, magnesium, aluminum). Lead
was identified in the solder and aerosol of two brands of EHs (up to 0.165 MUg/10
puffs). CONCLUSION: These data show that EC/EH aerosols contain a mixture of
elements, including heavy metals, with concentrations often significantly higher
than in conventional cigarette smoke. While the health effects of inhaling
mixtures of heated metals is currently not known, these data will be valuable in
future risk assessments involving EC/EH elements/metals.
PMID- 28414731
TI - A hyper-temporal remote sensing protocol for high-resolution mapping of
ecological sites.
AB - Ecological site classification has emerged as a highly effective land management
framework, but its utility at a regional scale has been limited due to the
spatial ambiguity of ecological site locations in the U.S. or the absence of
ecological site maps in other regions of the world. In response to these
shortcomings, this study evaluated the use of hyper-temporal remote sensing
(i.e., hundreds of images) for high spatial resolution mapping of ecological
sites. We posit that hyper-temporal remote sensing can provide novel insights
into the spatial variability of ecological sites by quantifying the temporal
response of land surface spectral properties. This temporal response provides a
spectral 'fingerprint' of the soil-vegetation-climate relationship which is
central to the concept of ecological sites. Consequently, the main objective of
this study was to predict the spatial distribution of ecological sites in a semi
arid rangeland using a 28-year time series of normalized difference vegetation
index from Landsat TM 5 data and modeled using support vector machine
classification. Results from this study show that support vector machine
classification using hyper-temporal remote sensing imagery was effective in
modeling ecological site classes, with a 62% correct classification. These
results were compared to Gridded Soil Survey Geographic database and expert
delineated maps of ecological sites which had a 51 and 89% correct
classification, respectively. An analysis of the effects of ecological state on
ecological site misclassifications revealed that sites in degraded states (e.g.,
shrub-dominated/shrubland and bare/annuals) had a higher rate of
misclassification due to their close spectral similarity with other ecological
sites. This study identified three important factors that need to be addressed to
improve future model predictions: 1) sampling designs need to fully represent the
range of both within class (i.e., states) and between class (i.e., ecological
sites) spectral variability through time, 2) field sampling protocols that
accurately characterize key soil properties (e.g., texture, depth) need to be
adopted, and 3) additional environmental covariates (e.g. terrain attributes)
need to be evaluated that may help further differentiate sites with similar
spectral signals. Finally, the proposed hyper-temporal remote sensing framework
may provide a standardized approach to evaluate and test our ecological site
concepts through examining differences in vegetation dynamics in response to
climatic variability and other drivers of land-use change. Results from this
study demonstrate the efficacy of the hyper-temporal remote sensing approach for
high resolution mapping of ecological sites, and highlights its utility in terms
of reduced cost and time investment relative to traditional manual mapping
approaches.
PMID- 28414732
TI - Active transforming growth factor-beta2 in the aqueous humor of posterior
polymorphous corneal dystrophy patients.
AB - PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is characterized by
abnormal proliferation of corneal endothelial cells. It was shown that TGF-beta2
present in aqueous humor (AH) could help maintaining the corneal endothelium in a
G1-phase-arrest state. We wanted to determine whether the levels of this protein
are changed in AH of PPCD patients. METHODS: We determined the concentrations of
active TGF-beta2 in the AH of 29 PPCD patients (42 samples) and 40 cadaver
controls (44 samples) by ELISA. For data analysis the PPCD patients were divided
based on either the molecular genetic cause of their disease as PPCD1 (37
samples), PPCD3 (1 sample) and PPCDx (not linked to a known PPCD loci, 4 samples)
or on the presence (17 samples) or absence (25 samples) of secondary glaucoma or
on whether they had undergone penetrating keratoplasty (PK, 32 samples) or
repeated PK (rePK, 7 samples). RESULTS: The level of active TGF-beta2 in the AH
of all PPCD patients (mean +/- SD; 386.98 +/- 114.88 pg/ml) in comparison to the
control group (260.95 +/- 112.43 pg/ml) was significantly higher (P = 0.0001).
Compared to the control group, a significantly higher level of active TGF-beta2
was found in the PPCD1 (P = 0.0005) and PPCDx (P = 0.0022) groups. Among patients
the levels of active TGF-beta2 were not significantly affected by gender, age,
secondary glaucoma or by the progression of dystrophy when one or repeated PK
were performed. CONCLUSION: The levels of active TGF-beta2 in the AH of PPCD
patients are significantly higher than control values, and thus the increased
levels of TGF-beta2 could be a consequence of the PPCD phenotype and can be
considered as another feature characterizing this disease.
PMID- 28414733
TI - Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique
approach and systematic review.
AB - INTRODUCTION: Antibodies targeting the inward-rectifying potassium channel KIR4.1
have been associated with multiple sclerosis (MS) but studies using diverse
techniques have failed to replicate this association. The detection of these
antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse
technical approaches may account for the disparity of results. We aimed to
replicate the association using three different approaches to overcome the
technical limitations of a single technique. We also performed a systematic
review to examine the association of anti-KIR4.1 antibodies with MS. METHODS:
Serum samples from patients with MS (n = 108) and controls (n = 77) were tested
for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with
the low-glycosylated fraction of recombinant KIR4.1 purified from transfected
HEK293 cells according to original protocols; 2) by immunocytochemistry using
KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.
transfected MO3.13 oligodendrocyte cell line. We developed a systematic review
and meta-analysis of the association of anti-KIR4.1 antibodies with MS according
to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines. RESULTS: We did not detect anti-KIR4.1 antibodies in the MS
patients or in controls using ELISA. Neither did we detect any significant
reactivity against the antigen on the cell surface using the KIR4.1-transfected
HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective
controlled studies in the systematic review. Only three studies showed a positive
association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity
between studies precluded meta-analysis of their results. CONCLUSION: We found no
association between anti-KIR4.1 antibody positivity and MS. Although this lack of
replication may be due to technical limitations, evidence from our study and
others is mounting against the role of KIR4.1 as a relevant MS autoantigen.
PMID- 28414735
TI - The coexistence of traditional medicine and biomedicine: A study with local
health experts in two Brazilian regions.
AB - This study investigated the combined use of traditional medicine and biomedicine
by local experts in Chapada do Araripe communities (Ceara State) and maroon
communities (Santa Catarina State), Brazil. The objective was to understand the
perception of local health specialists regarding the number of healers, demand
for healers and use of medicinal plants, and the dependence of different
environments to obtain such plants. We also aimed to understand the role of
medicinal plants to treat different categories of diseases and if there is a
complementary use of medicinal plants and allopathic biomedicine, according to
the context of each group. The research was conducted with local health
specialists that answered structured interviews, created free lists and
participated in guided tours to collect cited plants. Sixty-six local health
specialists were identified in the Araripe communities and 22 specialists in the
maroon communities. In the maroon communities, a greater number of specialists
thought there was a decrease in the number and demand for healers, as well as the
use of medicinal plants, due to changes in traditional livelihoods, since they
are located in a region where the effects of the modernization were more intense.
In the Chapada do Araripe communities the specialists knew more plants extracted
from native vegetation, whereas in the maroon communities cultivated plants were
better known, which may reflect the environmental conditions and the history of
each region. Medicinal plants are preferred to treat simpler health problems that
do not require medical care, such as gastrointestinal problems, general pain,
flues and colds. The biomedicine is used principally for problems with blood
pressure, general pains and endocrine and nutritional diseases. Even with the
particularities of each region, in general the use of medicinal plants and
biomedicines occurred in a complementary form in both regions; however, this
coexistence may result from these different contexts. This study also found that
there was knowledge and appreciation for traditional health practices in both
regions.
PMID- 28414734
TI - microRNAs as reference genes for quantitative PCR in cotton.
AB - Cotton (Gossypium hirsutum) is the most important non-food plant in the world.
Studies concerning the fiber quality and plant fitness of cotton at molecular
level depend on high sensitive and reproducible gene-expression assays. However,
only a few reports have described genes suitable for normalizing gene expression
data. In this study, we report for the first time that microRNAs (miRNAs) are
reliable reference genes (RGs) for cotton gene expression normalization in
quantitative real-time reverse transcription (RT)-PCR. The stability of cotton
miRNAs was assayed in root, stem, leaf and flower samples from three different
cultivars [FiberMax (FM966), Delta Opal (DO) and Cedro] and under conditions of
biotic stress caused by infection with Cotton leafroll dwarf virus (CLRDV). The
stability of mRNAs already described as reference genes in cotton was also
assessed. The geNorm, NormFinder, BestKeeper and DeltaCt algorithms were used to
select the best reference genes. In 8 of the 12 sets tested, miRNAs (miR172, 168
and 390) were found to be the best RGs. To validate the best selected RGs,
miR159, miR164, miR2118, miR2910, miR3476, GhDCL2 and GhDCL4 expression levels
were evaluated under biotic stress conditions, and miR164 and a putative myo
inositol oxigenase gene (GhMIOX) were assessed in leaves and flowers. The RGs
selected in this work proved to be excellent reference genes in the two cases
studied. Our results support the use of miRNAs as reference genes for miRNA and
protein-coding genes.
PMID- 28414736
TI - Catchment vegetation and temperature mediating trophic interactions and
production in plankton communities.
AB - Climatic factors influence the interactions among trophic levels in an ecosystem
in multiple ways. However, whereas most studies focus on single factors in
isolation, mainly due to interrelation and correlation among drivers complicating
interpretation and analyses, there are still only few studies on how multiple
ecosystems respond to climate related factors at the same time. Here, we use a
hierarchical Bayesian model with a bioenergetic predator-prey framework to study
how different climatic factors affect trophic interactions and production in
small Arctic lakes. Natural variation in temperature and catchment land-cover was
used as a natural experiment to exemplify how interactions between and production
of primary producers (phytoplankton) and grazers (zooplankton) are driven by
direct (temperature) and indirect (catchment vegetation) factors, as well as the
presence or absence of apex predators (fish). The results show that increased
vegetation cover increased phytoplankton growth rate by mediating lake nutrient
concentration. At the same time, increased temperature also increased grazing
rates by zooplankton. Presence of fish increased zooplankton mortality rates,
thus reducing grazing. The Arctic is currently experiencing an increase in both
temperature and shrub vegetation cover due to climate change, a trend, which is
likely to continue. Our results point towards a possible future general weakening
of zooplankton grazing on phytoplankton and greening of arctic lakes with
increasing temperatures. At the same time, the impact of the presence of an apex
predator indicate considerable local variation in the response. This makes
direction and strength of global change impacts difficult to forecast.
PMID- 28414737
TI - Peer norm guesses and self-reported attitudes towards performance-related pay.
AB - Due to a variety of reasons, people see themselves differently from how they see
others. This basic asymmetry has broad consequences. It leads people to judge
themselves and their own behavior differently from how they judge others and
others' behavior. This research, first, studies the perceptions and attitudes of
Greek Public Sector employees towards the introduction of Performance-Related Pay
(PRP) systems trying to reveal whether there is a divergence between individual
attitudes and guesses on peers' attitudes. Secondly, it is investigated whether
divergence between own self-reported and peer norm guesses could mediate the
acceptance of the aforementioned implementation once job status has been
controlled for. This study uses a unique questionnaire of 520 observations which
was designed to address the questions outlined in the preceding lines. Our
econometric results indicate that workers have heterogeneous attitudes and hold
heterogeneous beliefs on others' expectations regarding a successful
implementation of PRP. Specifically, individual perceptions are less skeptical
towards PRP than are beliefs on others' attitudes. Additionally, we found that
managers are significantly more optimistic than lower rank employees regarding
the expected success of PRP systems in their jobs. However, they both expect
their peers to be more negative than they themselves are.
PMID- 28414738
TI - Barriers and facilitators for men to attend prenatal care and obtain HIV
voluntary counseling and testing in Brazil.
AB - BACKGROUND: Providing HIV voluntary counseling and testing (VCT) to men who
attend their partner's prenatal care is an intervention with potential to reduce
HIV transmission to women and infants during the vulnerable period of pregnancy.
Little is known about the acceptability of this intervention in global settings
outside of Africa. METHODS: We conducted in-depth qualitative interviews to
evaluate potential barriers and facilitators to prenatal care attendance for HIV
VCT with 20 men who did and 15 men who did not attend prenatal care with their
partners at Hospital Conceicao in Porto Alegre, Brazil. Men were recruited at the
labor and delivery unit at Hospital Conceicao via a scripted invitation while
visiting their newborn infant. Interviews lasted from 35-55 minutes and were
conducted in Portuguese by a local resident trained extensively in qualitative
methods. All interviews were transcribed verbatim, translated, and then analyzed
using Atlast.ti software. An analysis of themes was then conducted using direct
quotes and statements. We applied and adapted the AIDS Risk Reduction Theoretical
Model and HIV Testing Decisions Model to the qualitative data to identify themes
in the 35 interviews. RESULTS: If offered HIV testing during prenatal care, all
men in both groups stated they would accept this intervention. Yet, individual,
relationship and systemic factors were identified that affect these Brazilian
men's decision to attend prenatal care, informing our final conceptual model. The
men interviewed had a general understanding of the value of HIV prevention of
mother to child transmission. They also described open and communicative
relationships with their significant others and displayed a high level of
enthusiasm towards optimizing the health of their expanding family. The major
barriers to attending prenatal care included perceived stigma against HIV
infected individuals, men's lack of involvement in planning of the pregnancy as
well as inconvenient scheduling of prenatal care, due to conflicting work
schedules. CONCLUSIONS: Brazilian men displayed high levels of HIV-related
knowledge as well as open communication about HIV testing; especially when
compared to findings from African studies. Future efforts should reorient
prenatal care towards providing care to the entire family with a clear focus on
protecting the infant from preventable diseases. Formally inviting men to
prenatal care and providing them an acceptable medical excuse from work may
enhance male involvement.
PMID- 28414740
TI - Cryopreserved human aortic root allografts arterial wall: Structural changes
occurring during thawing.
AB - BACKGROUND: The aim of our experimental work was to assess morphological changes
of arterial wall that arise during different thawing protocols of a cryopreserved
human aortic root allograft (CHARA) arterial wall. METHODS: The experiment was
performed on CHARAs. Two thawing protocols were tested: 1, CHARAs were thawed at
a room temperature at +23 degrees C; 2, CHARAs were placed directly into a water
bath at +37 degrees C. MICROSCOPIC SAMPLES PREPARATION: After fixation, all
samples were washed in distilled water for 5 min, and dehydrated in a graded
ethanol series (70, 85, 95, and 100%) for 5 min at each level. The tissue samples
were then immersed in 100% hexamethyldisilazane for 10 minutes and air dried in
an exhaust hood at room temperature. Processed samples were mounted on stainless
steel stubs, coated with gold. RESULTS: Thawing protocol 1: All 6 (100%) samples
showed loss of the endothelium and damage to the subendothelial layers with
randomly dispersed circular defects and micro-fractures without smooth muscle
cells contractions in the tunica media. Thawing protocol 2: All 6 (100%) samples
showed loss of endothelium from the luminal surface, longitudinal corrugations in
the direction of blood flow caused by smooth muscle cells contractions in the
tunica media with frequent fractures in the subendothelial layer. CONCLUSION: All
the samples thawed at the room temperature showed smaller structural damage to
the CHARA arterial wall with no smooth muscle cell contraction in tunica media
when compared to the samples thawed in a water bath.
PMID- 28414739
TI - An in silico pan-genomic probe for the molecular traits behind Lactobacillus
ruminis gut autochthony.
AB - As an ecological niche, the mammalian intestine provides the ideal habitat for a
variety of bacterial microorganisms. Purportedly, some commensal genera and
species offer a beneficial mix of metabolic, protective, and structural processes
that help sustain the natural digestive health of the host. Among these sort of
gut inhabitants is the Gram-positive lactic acid bacterium Lactobacillus ruminis,
a strict anaerobe with both pili and flagella on its cell surface, but also known
for being autochthonous (indigenous) to the intestinal environment. Given that
the molecular basis of gut autochthony for this species is largely unexplored and
unknown, we undertook a study at the genome level to pinpoint some of the
adaptive traits behind its colonization behavior. In our pan-genomic probe of L.
ruminis, the genomes of nine different strains isolated from human, bovine,
porcine, and equine host guts were compiled and compared for in silico analysis.
For this, we conducted a geno-phenotypic assessment of protein-coding genes, with
an emphasis on those products involved with cell-surface morphology and anaerobic
fermentation and respiration. We also categorized and examined the core and
accessory genes that define the L. ruminis species and its strains. Here, we made
an attempt to identify those genes having ecologically relevant phenotypes that
might support or bring about intestinal indigenousness.
PMID- 28414741
TI - Effects of music on arousal during imagery in elite shooters: A pilot study.
AB - Beneficial effects of music on several performance-related aspects of sport have
been reported, but the processes involved are not well understood. The purpose of
the present study was to investigate effects of relaxing and arousing classical
music on physiological indicators and subjective perceptions of arousal during
imagery of a sport task. First, appropriate music excerpts were selected. Then,
12 skilled shooters performed shooting imagery while listening to the three
preselected music excerpts in randomized order. Participants' galvanic skin
response, peripheral temperature, and electromyography were monitored during
music played concurrently with imagery. Subjective music ratings and
physiological measures showed, as hypothesized, that unfamiliar relaxing music
was the most relaxing and unfamiliar arousing music was the most arousing.
Researchers should examine the impact of unfamiliar relaxing and arousing music
played during imagery on subsequent performance in diverse sports. Practitioners
can apply unfamiliar relaxing and arousing music with imagery to manipulate
arousal level.
PMID- 28414742
TI - To electrify bilingualism: Electrophysiological insights into bilingual metaphor
comprehension.
AB - Though metaphoric language comprehension has previously been investigated with
event-related potentials, little attention has been devoted to extending this
research from the monolingual to the bilingual context. In the current study,
late proficient unbalanced Polish (L1)-English (L2) bilinguals performed a
semantic decision task to novel metaphoric, conventional metaphoric, literal, and
anomalous word pairs presented in L1 and L2. The results showed more pronounced
P200 amplitudes to L2 than L1, which can be accounted for by differences in the
subjective frequency of the native and non-native lexical items. Within the early
N400 time window (300-400 ms), L2 word dyads evoked delayed and attenuated
amplitudes relative to L1 word pairs, possibly indicating extended lexical search
during foreign language processing, and weaker semantic interconnectivity for L2
compared to L1 words within the memory system. The effect of utterance type was
observed within the late N400 time window (400-500 ms), with smallest amplitudes
evoked by literal, followed by conventional metaphoric, novel metaphoric, and
anomalous word dyads. Such findings are interpreted as reflecting more resource
intensive cognitive mechanisms governing novel compared to conventional metaphor
comprehension in both the native and non-native language. Within the late
positivity time window (500-800 ms), Polish novel metaphors evoked reduced
amplitudes relative to literal utterances. In English, on the other hand, this
effect was observed for both novel and conventional metaphoric word dyads. This
finding might indicate continued effort in information retrieval or access to the
non-literal route during novel metaphor comprehension in L1, and during novel and
conventional metaphor comprehension in L2. Altogether, the present results point
to decreased automaticity of cognitive mechanisms engaged in non-native and non
dominant language processing, and suggest a decreased sensitivity to the levels
of conventionality of metaphoric meanings in late proficient unbalanced bilingual
speakers.
PMID- 28414743
TI - The ET-1-mediated carbonylation and degradation of ANXA1 induce inflammatory
phenotype and proliferation of pulmonary artery smooth muscle cells in HPS.
AB - Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver
disease, which markedly increases mortality. Pulmonary vascular remodelling (PVR)
induced by circulating mediators plays an important role in the pathogenesis of
HPS, while the underlying mechanism remains undefined. In the present study, we
reported that endothelin-1 (ET-1) is up-regulated and annexin A1(ANXA1) is down
regulated in HPS rat, and ET-1 decreases the ANXA1 expression in a dose-dependent
manner in rat pulmonary arterial smooth muscle cells (PASMCs). Then, we showed
that ANXA1 can decrease nuclear p-ERK1/2 accumulation and decrease the cyclin D1
expression, thus resulting in the subsequent inhibition of PASMCs proliferation.
As previously reported, we confirmed that ET-1 decreases the ANXA1 protein levels
by the carbonylation and degradation of ANXA1. In conclusion, our research links
the signaling cascade of ET1-ANXA1-cell proliferation to a potential therapeutic
strategy for blocking IPS-associated PVR.
PMID- 28414744
TI - Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in
the visceral leishmaniasis vector Phlebotomus argentipes.
AB - BACKGROUND: Indoor residual spraying (IRS) with DDT has been the primary strategy
for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in
India but efficacy may be compromised by resistance. Synthetic pyrethroids are
now being introduced for IRS, but with a shared target site, the para voltage
gated sodium channel (VGSC), mutations affecting both insecticide classes could
provide cross-resistance and represent a threat to sustainable IRS-based disease
control. METHODOLOGY/PRINCIPAL FINDINGS: A region of the Vgsc gene was sequenced
in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance
(kdr) mutations were detected at codon 1014 (L1014F and L1014S), each common in
mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear
largely recessive, but as homozygotes (especially 1014F/F) or as 1014F/S
heterozygotes exert a strong effect on DDT resistance, and significantly predict
survivorship to class II pyrethroids in short-duration bioassays. The mutations
are present at high frequency in wild P. argentipes populations from Bihar, with
1014F significantly more common in higher VL areas. CONCLUSIONS/SIGNIFICANCE: The
Vgsc mutations detected appear to be a primary mechanism underlying DDT
resistance in P. argentipes and a contributory factor in reduced pyrethroid
susceptibility, suggesting a potential impact if P. argentipes are subjected to
suboptimal levels of pyrethroid exposure, or additional resistance mechanisms
evolve. The assays to detect kdr frequency changes provide a sensitive, high
throughput monitoring tool to detecting spatial and temporal variation in
resistance in P. argentipes.
PMID- 28414745
TI - Mapping the SRS-22r questionnaire onto the EQ-5D-5L utility score in patients
with adolescent idiopathic scoliosis.
AB - This is a prospective study to establish prediction models that map the refined
Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ
5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients.
Comparison of treatment outcomes in AIS can be determined by cost-utility
analysis. However, the mainstay spine-specific health-related quality of life
outcome measure, the SRS-22r questionnaire does not provide utility assessment.
In this study, AIS patients were prospectively recruited to complete both the EQ
5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares
regression was undertaken to develop mapping models, which the validity and
robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D
5L utility scores were regressed on demographics, Cobb angle, curve types,
treatment modalities, and five domains of the SRS-22r questionnaire. Three models
were developed using stepwise selection method. EQ-5D-5L scores were regressed on
1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and
interaction terms, and 3) as per 2 plus demographic and clinical characteristics.
Model goodness-of-fit was assessed using R-square, adjusted R-square, and
information criteria; whereas the predictive performance was evaluated using root
mean square error (RMSE), mean absolute error (MAE), and the proportion of
absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients
with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by
four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and
'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in
Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%).
Three models demonstrated an acceptance predictive performance in error analysis
applying 10-fold cross-validation to three models where RMSE and MAE were between
0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore
recommended out of three mapping models established in this paper. To our
knowledge, this is the first study to map a spine-specific health-related quality
of life measure onto EQ-5D-5L for AIS patients. With the consideration and
incorporation of demographic and clinical characteristics, over 60% variance
explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L
utility scores from existing SRS-22r data for health economic appraisal of
different treatment options.
PMID- 28414746
TI - Local Th17/IgA immunity correlate with protection against intranasal infection
with Streptococcus pyogenes.
AB - Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide
array of infections. Respiratory transmission via droplets is the most common
mode of transmission but it may also infect the host via other routes such as
lesions in the skin. To advance the development of a future vaccine against GAS,
it is therefore important to investigate how protective immunity is related to
the route of vaccine administration. To explore this, we examined whether a
parenterally administered anti-GAS vaccine could protect against an intranasal
GAS infection or if this would require locally primed immunity. We foundd that a
parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal
infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently
protected against an intraperitoneal GAS infection. However, the same vaccine
administered via the intranasal route was able to induce protection against
repeated intranasal GAS infections in a murine challenge model. The lack of
intranasal protection induced by the parenteral vaccine correlated with a reduced
mucosal recall response at the site of infection. Taken together, our results
demonstrate that locally primed immunity is important for the defense against
intranasal infection with Streptococcus pyogenes.
PMID- 28414747
TI - Hierarchical and coupling model of factors influencing vessel traffic flow.
AB - Understanding the characteristics of vessel traffic flow is crucial in
maintaining navigation safety, efficiency, and overall waterway transportation
management. Factors influencing vessel traffic flow possess diverse features such
as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To
reveal the impact mechanism of the factors influencing vessel traffic flow, a
hierarchical model and a coupling model are proposed in this study based on the
interpretative structural modeling method. The hierarchical model explains the
hierarchies and relationships of the factors using a graph. The coupling model
provides a quantitative method that explores interaction effects of factors using
a coupling coefficient. The coupling coefficient is obtained by determining the
quantitative indicators of the factors and their weights. Thereafter, the data
obtained from Port of Tianjin is used to verify the proposed coupling model. The
results show that the hierarchical model of the factors influencing vessel
traffic flow can explain the level, structure, and interaction effect of the
factors; the coupling model is efficient in analyzing factors influencing traffic
volumes. The proposed method can be used for analyzing increases in vessel
traffic flow in waterway transportation system.
PMID- 28414748
TI - Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA
nephropathy.
AB - Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in
the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is
appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b
staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in
assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown.
Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou
University and Peking University First Hospital diagnosed with IgAN in CKD stage
3 were enrolled and successfully followed up. Cox proportional hazards model was
used to analyze hazard ratios of reaching the composite endpoints (doubling of
serum creatinine, end-stage renal disease: estimated glomerular filtration rate
(eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for
patients with different eGFR and risk factors affecting composite endpoints. The
Kaplan-Meier method was used to calculate the cumulative renal survival rate of
patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio
increased sharply for patients in CKD stage 3 who reached the composite
endpoints. Renal injury and prognosis were significantly different between
patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting
prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to
assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients
with CKD stage 3 into G3a and G3b is very useful to help understand disease
conditions and for predicting the risk for disease progression.
PMID- 28414749
TI - Sequence variability of the respiratory syncytial virus (RSV) fusion gene among
contemporary and historical genotypes of RSV/A and RSV/B.
AB - BACKGROUND: The fusion (F) protein of RSV is the major vaccine target. This
protein undergoes a conformational change from pre-fusion to post-fusion. Both
conformations share antigenic sites II and IV. Pre-fusion F has unique antigenic
sites p27, o, alpha2alpha3beta3beta4, and MPE8; whereas, post-fusion F has unique
antigenic site I. Our objective was to determine the antigenic variability for
RSV/A and RSV/B isolates from contemporary and historical genotypes compared to a
historical RSV/A strain. METHODS: The F sequences of isolates from GenBank,
Houston, and Chile (N = 1,090) were used for this analysis. Sequences were
compared pair-wise to a reference sequence, a historical RSV/A Long strain.
Variability (calculated as %) was defined as changes at each amino acid (aa)
position when compared to the reference sequence. Only aa at antigenic sites with
variability >=5% were reported. RESULTS: A total of 1,090 sequences (822 RSV/A
and 268 RSV/B) were analyzed. When compared to the reference F, those domains
with the greatest number of non-synonymous changes included the signal peptide,
p27, heptad repeat domain 2, antigenic site o, and the transmembrane domain.
RSV/A subgroup had 7 aa changes in the antigenic sites: site I (N = 1), II (N =
1), p27 (N = 4), alpha2alpha3beta3beta4(AM14) (N = 1), ranging in frequency from
7-91%. In comparison, RSV/B had 19 aa changes in antigenic sites: I (N = 3), II
(N = 1), p27 (N = 9), o (N = 4), alpha2alpha3beta3beta4(AM14) (N = 1), and MPE8
(N = 1), ranging in frequency from 79-100%. DISCUSSION: Although antigenic sites
of RSV F are generally well conserved, differences are observed when comparing
the two subgroups to the reference RSV/A Long strain. Further, these
discrepancies are accented in the antigenic sites in pre-fusion F of RSV/B
isolates, often occurring with a frequency of 100%. This could be of importance
if a monovalent F protein from the historical GA1 genotype of RSV/A is used for
vaccine development.
PMID- 28414751
TI - The influence of journal submission guidelines on authors' reporting of
statistics and use of open research practices.
AB - From January 2014, Psychological Science introduced new submission guidelines
that encouraged the use of effect sizes, estimation, and meta-analysis (the "new
statistics"), required extra detail of methods, and offered badges for use of
open science practices. We investigated the use of these practices in empirical
articles published by Psychological Science and, for comparison, by the Journal
of Experimental Psychology: General, during the period of January 2013 to
December 2015. The use of null hypothesis significance testing (NHST) was
extremely high at all times and in both journals. In Psychological Science, the
use of confidence intervals increased markedly overall, from 28% of articles in
2013 to 70% in 2015, as did the availability of open data (3 to 39%) and open
materials (7 to 31%). The other journal showed smaller or much smaller changes.
Our findings suggest that journal-specific submission guidelines may encourage
desirable changes in authors' practices.
PMID- 28414750
TI - Effect of transcription factor resource sharing on gene expression noise.
AB - Gene expression is intrinsically a stochastic (noisy) process with important
implications for cellular functions. Deciphering the underlying mechanisms of
gene expression noise remains one of the key challenges of regulatory biology.
Theoretical models of transcription often incorporate the kinetics of how
transcription factors (TFs) interact with a single promoter to impact gene
expression noise. However, inside single cells multiple identical gene copies as
well as additional binding sites can compete for a limiting pool of TFs. Here we
develop a simple kinetic model of transcription, which explicitly incorporates
this interplay between TF copy number and its binding sites. We show that TF
sharing enhances noise in mRNA distribution across an isogenic population of
cells. Moreover, when a single gene copy shares it's TFs with multiple competitor
sites, the mRNA variance as a function of the mean remains unaltered by their
presence. Hence, all the data for variance as a function of mean expression
collapse onto a single master curve independent of the strength and number of
competitor sites. However, this result does not hold true when the competition
stems from multiple copies of the same gene. Therefore, although previous studies
showed that the mean expression follows a universal master curve, our findings
suggest that different scenarios of competition bear distinct signatures at the
level of variance. Intriguingly, the introduction of competitor sites can
transform a unimodal mRNA distribution into a multimodal distribution. These
results demonstrate the impact of limited availability of TF resource on the
regulation of noise in gene expression.
PMID- 28414752
TI - An angiogenesis platform using a cubic artificial eggshell with patterned blood
vessels on chicken chorioallantoic membrane.
AB - The chorioallantoic membrane (CAM) containing tiny blood vessels is an
alternative to large animals for studies involving angiogenesis and tissue
engineering. However, there is no technique to design the direction of growing
blood vessels on the CAM at the microscale level for tissue engineering
experiments. Here, a methodology is provided to direct blood vessel formation on
the surface of a three-dimensional egg yolk using a cubic artificial eggshell
with six functionalized membranes. A structure on the lateral side of the
eggshell containing a straight channel and an interlinked chamber was designed,
and the direction and formation area of blood vessels with blood flow was
artfully defined by channels with widths of 70-2000 MUm, without sharply reducing
embryo viability. The relationship between the size of interlinked chamber and
the induction of blood vessels was investigated to establish a theory of design.
Role of negative and positive pressure in the induction of CAM with blood vessels
was investigated, and air pressure change in the culture chamber was measured to
demonstrate the mechanism for blood vessel induction. Histological evaluation
showed that components of CAM including chorionic membrane and blood vessels were
induced into the channels. Based on our design theory, blood vessels were induced
into arrayed channels, and channel-specific injection and screening were
realized, which demonstrated proposed applications. The platform with position-
and space-controlled blood vessels is therefore a powerful tool for biomedical
research, which may afford exciting applications in studies involved in local
stimulation of blood vessel networks and those necessary to establish a living
system with blood flow from a beating heart.
PMID- 28414753
TI - Sustained low peritoneal effluent CCL18 levels are associated with preservation
of peritoneal membrane function in peritoneal dialysis.
AB - Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal
sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications.
Combining clinical and peritoneal transport data with the measurement of
molecular biomarkers, such as the chemokine CCL18, would improve the complex
diagnosis and management of PMF. We measured CCL18 levels in 43 patients'
effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by
retrospective longitudinal study, and evaluated their association with PMF/EPS
development and peritoneal risk factors. To confirm the trends observed in the
longitudinal study, a cross-sectional study was performed on 61 isolated samples
from long-term (more than 3 years) patients treated with PD. We observed that the
patients with no membrane dysfunction showed sustained low CCL18 levels in
peritoneal effluent over time. An increase in CCL18 levels at any time was
predictive of PMF development (final CCL18 increase over baseline, p = .014; and
maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent
under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels
were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067).
Moreover, CCL18 levels in effluent at year 3 of PD were independently associated
with a risk of PMF development, adjusted for the classical (water and creatinine)
peritoneal transport parameters. These trends were confirmed in a cross-sectional
study of 61 long-term patients treated with PD. In conclusion, our study shows
the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to
predict PMF and suggests CCL18 as a new marker and mediator of this serious
condition as well as a new potential therapeutic target.
PMID- 28414754
TI - Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a
national sample of community-dwellers: A prospective cohort study.
AB - We examined the individual and synergistic effects of type 2 diabetes and
elevated depressive symptoms on memory and executive function trajectories over
10 and eight years of follow-up, respectively. Our sample comprised 10,524
community-dwellers aged >=50 years in 2002-03 from the English Longitudinal Study
of Ageing. With respect to memory (word recall), participants with either
diabetes or elevated depressive symptoms recalled significantly fewer words
compared with those free of these conditions (reference category), but more words
compared with those with both conditions. There was a significant acceleration in
the rate of memory decline in participants aged 50-64 years with both conditions
(-0.27, 95% CI, -0.45 to -0.08, per study wave), which was not observed in those
with either condition or aged >=65 years. With respect to executive function
(animal naming), participants aged >=65 years with diabetes or those with
elevated depressive symptoms named significantly fewer animals compared with the
reference category, while those with both conditions named fewer animals compared
with any other category. The rate of executive function decline was significantly
greater in participants with both conditions (-0.54, 95% CI, -0.99 to -0.10; and
0.71, 95% CI, -1.16 to -0.27, per study wave, for those aged 50-64 and >=65
years, respectively), but not in participants with either condition. Diabetes and
elevated depressive symptoms are inversely associated with memory and executive
function, but, individually, do not accelerate cognitive decline. The co
occurrence of diabetes and elevated depressive symptoms significantly accelerates
cognitive decline over time, especially among those aged 50-64 years.
PMID- 28414755
TI - Childhood socioeconomic status and childhood maltreatment: Distinct associations
with brain structure.
AB - The present study examined the relationship between childhood socioeconomic
status (SES), childhood maltreatment, and the volumes of the hippocampus and
amygdala between the ages of 25 and 36 years. Previous work has linked both low
SES and maltreatment with reduced hippocampal volume in childhood, an effect
attributed to childhood stress. In 46 adult subjects, only childhood
maltreatment, and not childhood SES, predicted hippocampal volume in regression
analyses, with greater maltreatment associated with lower volume. Neither factor
was related to amygdala volume. When current SES and recent interpersonal
stressful events were also considered, recent interpersonal stressful events
predicted smaller hippocampal volumes over and above childhood maltreatment.
Finally, exploratory analyses revealed a significant sex by childhood SES
interaction, with women's childhood SES showing a significantly more positive
relation (less negative) with hippocampus volume than men's. The overall effect
of childhood maltreatment but not SES, and the sex-specific effect of childhood
SES, indicate that different forms of stressful childhood adversity affect brain
development differently.
PMID- 28414756
TI - Reduction in the copy number and expression level of the recurrent human
papillomavirus integration gene fragile histidine triad (FHIT) predicts the
transition of cervical lesions.
AB - Cervical cancer is the second most common cancer and the third leading cause of
cancer death in females worldwide, especially in developing countries. High risk
human papillomavirus (HR-HPV) infection causes cervical cancer and precancerous
cervical intraepithelial neoplasia (CIN). Integration of the HR-HPV genome into
the host chromatin is an important step in cervical carcinogenesis. The detection
of integrated papillomavirus sequences-PCR (DIPS-PCR) allowed us to explore HPV
integration in the human genome and to determine the pattern of this integration.
We performed DIPS-PCR for 4 cell lines including 3 cervical cancer cell lines and
40 tissue samples. Overall, 32 HR-HPV integration loci were detected in the
clinical samples and the HeLa and SiHa cell lines. Among all the integration
loci, we identified three recurrent integration loci: 3p14.2 (3 samples), 13q22.1
(2 samples and a SiHa cell line) and 8q24 (1 sample and a HeLa cell line). To
further explore the effect of HR-HPV integration in the 3p14.2 locus, we used
fluorescence in situ hybridization (FISH) to determine the copy number of the
3p14.2 locus and immunohistochemistry (IHC) to determine the protein expression
levels of the related FHIT gene in the clinical samples. Both the 3p14.2 locus
copy number and FHIT protein expression levels showed significant decreases when
CIN transitioned to cervical cancer. HPV copy number was also evaluated in these
clinical samples, and the copy number of HPV increased significantly between CIN
and cervical cancer samples. Finally, we employed receiver operating
characteristic curve (ROC curve) analysis to evaluate the potential of all these
indexes in distinguishing CIN and cervical cancer, and the HPV copy number, FHIT
copy number and FHIT protein expression levels have good diagnostic efficiencies.
PMID- 28414757
TI - Predictors of smoking among primary and secondary school students in Botswana.
AB - This study seeks to determine the prevalence and risk factors for smoking among
students aged 12-18 years in two cities in Botswana. Using a sample of 2554
students we adapted the Global Youth Tobacco Survey (GYTS) methodology to assess
students' smoking practices, knowledge, beliefs and attitudes. Logistic
regression models were used to evaluate factors associated with smoking. The
results revealed that 10% of students were current tobacco smokers with 29%
reporting having tried smoking. Self-image and acceptance by peers were the
strongest predictors of smoking overall (adjusted Odds Ratio [aOR]: 3.13, 95%,
Confidence Interval [CI]: 2.67-3.66). Intention to smoke or to continue to smoke
and perceived norms in conformity with smoking were also independently associated
with smoking (aOR: 1.81, 95% CI: 167-2.11 and aOR: 1.31, 95% CI: 1.10-1.57,
respectively). Perceived prevalence and exposure to smoking by peers and family
and access to tobacco products was stronger among females (aOR: 1.69, 95% CI:
1.52-1.91) compared to males (aOR: 0.93, 95% CI: 0.70-1.24). Our results indicate
that anti-tobacco interventions in Botswana should prioritize intra-personal
factors associated with smoking. Our findings also suggest that different
interventions targeting male and female students should be explored.
PMID- 28414758
TI - Early dialysis initiation does not improve clinical outcomes in elderly end-stage
renal disease patients: A multicenter prospective cohort study.
AB - BACKGROUND: The optimal timing for initiating dialysis in end-stage renal disease
(ESRD) is controversial, especially in the elderly. METHODS: 665 patients >=65
years old who began dialysis from August 2008 to February 2015 were prospectively
enrolled in the Clinical Research Center for End-Stage Renal Disease cohort
study. Participants were divided into 2 groups based on the median estimated
glomerular filtration rate at the initiation of dialysis. Propensity score
matching (PSM) was used to compare the overall survival rate, cardiovascular
events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results,
Karnofsky performance scale values, Beck's depression inventory values, and
subjective global assessments. RESULTS: The mean patient age was 72.0 years, and
61.7% of the patients were male. Overall, the cumulative survival rates were
lower in the early initiation group, although the difference was not significant
after PSM. Additionally, the survival rates of the 2 groups did not differ after
adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin,
serum calcium and phosphorus levels. Although the early initiation group showed a
lower physical component summary score on the KDQOL-36 3 months after dialysis,
the difference in scores was not significant 12 months after dialysis.
Furthermore, the difference was not significant after PSM. The Karnofsky
performance scale, Beck's depression inventory, and subjective global assessments
were not significantly different 3 and 12 months after dialysis initiation.
CONCLUSIONS: The timing of dialysis initiation is not associated with clinical
outcomes in elderly patients with ESRD.
PMID- 28414760
TI - Real benefit of a protective factor against dementia: Importance of controlling
for death. Example of sport practice.
AB - OBJECTIVES: To analyse the impact of a risk factor on several epidemiological
indicators of death and dementia; the example of sport practice is presented.
METHODS: A population of 3670 non-demented subjects living at home and aged 65
and older from the PAQUID study were followed for 22 years. Sport practice was
documented at baseline. Dementia (according to DSM-III-R criteria) and death were
assessed at each visit. Analyses were performed with an Illness-Death model,
providing results on the risks of dementia and death, probabilities and life
expectancies. RESULTS: A total of 743 subjects (20.2%) participated in regular
sport practice. During the follow-up, the proportion of death was lower in the
elderly people practicing sport (EPPS), whereas the proportion of incident
dementia cases was the same. The adjusted model showed a decreased risk of
dementia (HR = 0.84 (0.72-1.00)) and of death for non-demented subjects (HR =
0.61 (0.51-0.71)) for EPPS but a similar risk of death with dementia in both
sport groups. The probability of remaining alive without dementia was higher in
EPPS, whereas the probability of dying was lower. The mean lifetime without
dementia was 3 years higher for the EPPS, but the mean lifetime with dementia was
the same. DISCUSSION: A preventive measure on a protective factor that is more
effective for preventing death than dementia could lead to an increased lifetime
without dementia; however, the number of demented cases may remain unchanged,
even if the risk of developing dementia is reduced. This dynamic is important to
forecast the need for health care and social services for the elderly.
PMID- 28414759
TI - Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant,
with coronary artery disease.
AB - BACKGROUND: The genetic architecture of coronary artery disease has not been
fully elucidated, especially in Asian countries. Moyamoya disease is a
progressive cerebrovascular disease that is reported to be complicated by
coronary artery disease. Because most Japanese patients with moyamoya disease
carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be
a risk factor for coronary artery disease; however, this possibility has never
been tested. METHODS AND RESULTS: We genotyped the RNF213 p.R4810K variant in 956
coronary artery disease patients and 716 controls and tested the association
between p.R4810K and coronary artery disease. We also validated the association
in an independent population of 311 coronary artery disease patients and 494
controls. In the replication study, the p.R4810K genotypes were imputed from
genome-wide genotyping data based on the 1000 Genomes Project. We used
multivariate logistic regression analyses to adjust for well-known risk factors
such as dyslipidemia and smoking habits. In the primary study population, the
frequency of the minor variant allele was significantly higher in patients with
coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of
2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the
association remained significant, with an odds ratio of 2.90 (95% confidence
interval: 1.37-6.61; p = 0.005). In the replication study, the association was
significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence
interval: 1.16-21.53; p = 0.031), although it did not reach statistical
significance when further adjusted for risk factors (odds ratio = 3.82; 95%
confidence interval: 0.87-16.77; p = 0.076). CONCLUSIONS: The RNF213 p.R4810K
variant appears to be significantly associated with coronary artery disease in
the Japanese population.
PMID- 28414761
TI - Identification of a plasma metabolomic signature of thrombotic myocardial
infarction that is distinct from non-thrombotic myocardial infarction and stable
coronary artery disease.
AB - AIMS: Current non-invasive diagnostics for acute myocardial infarction (MI)
identify myocardial necrosis rather than the primary cause and therapeutic target
plaque disruption and resultant thrombosis. The aim of this study was to identify
changes specific to plaque disruption and pathological thrombosis that are
distinct from acute myocardial necrosis. METHODS AND RESULTS: We quantified 1,032
plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic
MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time
of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up)
time points. A statistical classifier was constructed utilizing baseline (T0)
abundances of a parsimonious set of 17 qualifying metabolites. Qualifying
metabolites were those that demonstrated a significant change between the
quiescent phase and the acute phase and that were distinct from any change seen
in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated
by 10-fold cross-validation was suggestive of high sensitivity and specificity
for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at
presentation. Nineteen metabolites demonstrated an intra-subject change from time
of acute thrombotic MI presentation to the quiescent state that was distinct from
any change measured in both the non-thrombotic MI and stable CAD subjects
undergoing cardiac catheterization over the same time course (false discovery
rate <5%). CONCLUSIONS: We have identified a candidate metabolic signature that
differentiates acute thrombotic MI from quiescent state after MI, from acute non
thrombotic MI, and from stable CAD. Further validation of these metabolites is
warranted given their potential as diagnostic biomarkers and novel therapeutic
targets for the prevention or treatment of acute MI.
PMID- 28414762
TI - Transcriptional networks are associated with resistance to Mycobacterium
tuberculosis infection.
AB - RATIONALE: Understanding mechanisms of resistance to M. tuberculosis (M.tb)
infection in humans could identify novel therapeutic strategies as it has for
other infectious diseases, such as HIV. OBJECTIVES: To compare the early
transcriptional response of M.tb-infected monocytes between Ugandan household
contacts of tuberculosis patients who demonstrate clinical resistance to M.tb
infection (cases) and matched controls with latent tuberculosis infection.
METHODS: Cases (n = 10) and controls (n = 18) were selected from a long-term
household contact study in which cases did not convert their tuberculin skin test
(TST) or develop tuberculosis over two years of follow up. We obtained genome
wide transcriptional profiles of M.tb-infected peripheral blood monocytes and
used Gene Set Enrichment Analysis and interaction networks to identify cellular
processes associated with resistance to clinical M.tb infection. MEASUREMENTS AND
MAIN RESULTS: We discovered gene sets associated with histone deacetylases that
were differentially expressed when comparing resistant and susceptible subjects.
We used small molecule inhibitors to demonstrate that histone deacetylase
function is important for the pro-inflammatory response to in-vitro M.tb
infection in human monocytes. CONCLUSIONS: Monocytes from individuals who appear
to resist clinical M.tb infection differentially activate pathways controlled by
histone deacetylase in response to in-vitro M.tb infection when compared to those
who are susceptible and develop latent tuberculosis. These data identify a
potential cellular mechanism underlying the clinical phenomenon of resistance to
M.tb infection despite known exposure to an infectious contact.
PMID- 28414763
TI - Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet
is associated with epigenetic and microbiome alterations.
AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity
associated with obesity and a precursor to steatohepatitis. However, the
contributions of gestational and early life influences on development of NAFLD
and NASH remain poorly appreciated. METHODS: Two independent studies were
performed to examine whether maternal over-nutrition via exposure to high fat
diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and
methionine choline deficient (MCD) diets in the offspring. Offspring of both
control diet- and HFD-fed dams were weaned onto control and HFD, creating four
groups. RESULTS: When compared to their control diet-fed littermates, offspring
of HF-dams weaned onto HFD gained greater body weight; had increased relative
liver weight and showed hepatic steatosis and inflammation. Similarly, this group
revealed significantly greater immune response and pro-fibrogenic gene expression
via RNA-seq. In parallel, 7-8 week old offspring were challenged with either
control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated
due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes.
Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed
persistent epigenetic changes in key genes in tissue development and metabolism
(Fgf21, Ppargc1beta) with maternal HFD and in cell adhesion and communication
(VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal
HFD also influenced gut microbiome profiles in offspring leading to a decrease in
alpha-diversity. Linear regression analysis revealed association between serum
ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum.
CONCLUSION: Our findings indicate that maternal HFD detrimentally alters
epigenetic and gut microbiome pathways to favor development of fatty liver
disease and its progressive sequelae.
PMID- 28414764
TI - Effects of UV-B radiation on leaf hair traits of invasive plants-Combining
historical herbarium records with novel remote sensing data.
AB - Ultraviolet-B (UV-B) radiation is a key but under-researched environmental factor
that initiates diverse responses in plants, potentially affecting their
distribution. To date, only a few macroecological studies have examined
adaptations of plant species to different levels of UV-B. Here, we combined
herbarium specimens of Hieracium pilosella L. and Echium vulgare L. with a novel
UV-B dataset to examine differences in leaf hair traits between the plants'
native and alien ranges. We analysed scans of 336 herbarium specimens using
standardized measurements of leaf area, hair density (both species) and hair
length (H. pilosella only). While accounting for other bioclimatic variables
(i.e. temperature, precipitation) and effects of herbivory, we examined whether
UV-B exposure explains the variability and geographical distribution of these
traits in the native (Northern Hemisphere) vs. the alien (Southern Hemisphere)
range. UV-B explained the largest proportion of the variability and geographical
distribution of hair length in H. pilosella (relative influence 67.1%), and hair
density in E. vulgare (66.2%). Corresponding with higher UV-B, foliar hairs were
25% longer for H. pilosella and 25% denser for E. vulgare in records from the
Southern as compared to those from the Northern Hemisphere. However, focusing on
each hemisphere separately or controlling for its effect in a regression
analysis, we found no apparent influence of UV-B radiation on hair traits. Thus,
our findings did not confirm previous experimental studies which suggested that
foliar hairs may respond to higher UV-B intensities, presumably offering
protection against detrimental levels of radiation. We cannot rule out UV-B
radiation as a possible driver because UV-B radiation was the only considered
variable that differed substantially between the hemispheres, while bioclimatic
conditions (e.g. temperature, precipitation) and other considered variables
(herbivory damage, collection date) were at similar levels. However, given that
either non-significant or inconclusive relationships were detected within
hemispheres, alternative explanations of the differences in foliar hairs are more
likely, including the effects of environment, genotypes or herbivory.
PMID- 28414765
TI - Validation of full-field optical coherence tomography in distinguishing malignant
and benign tissue in resected pancreatic cancer specimens.
AB - BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related
mortality in the United States. The minority of patients can undergo curative
intended surgical therapy due to progressive disease stage at time of diagnosis.
Nonetheless, tumor involvement of surgical margins is seen in up to 70% of
resections, being a strong negative prognostic factor. Real-time intraoperative
imaging modalities may aid surgeons to obtain tumor-free resection margins. Full
field optical coherence tomography (FF-OCT) is a promising diagnostic tool using
high-resolution white-light interference microscopy without tissue processing.
Therefore, we composed an atlas of FF-OCT images of malignant and benign
pancreatic tissue, and investigated the accuracy with which the pathologists
could distinguish these. MATERIALS AND METHODS: One hundred FF-OCT images were
collected from specimens of 29 patients who underwent pancreatic resection for
various indications between 2014 and 2016. One experienced gastrointestinal
pathologist and one pathologist in training scored independently the FF-OCT
images as malignant or benign blinded to the final pathology conclusion. Results
were compared to those obtained with standard hematoxylin and eosin (H&E) slides.
RESULTS: Overall, combined test characteristics of both pathologists showed a
sensitivity of 72%, specificity of 74%, positive predictive value of 69%,
negative predictive value of 79% and an overall accuracy of 73%. In the subset of
pancreatic ductal adenocarcinoma patients, 97% of the FF-OCT images (n = 35) were
interpreted as tumor by at least one pathologist. Moreover, normal pancreatic
tissue was recognised in all cases by at least one pathologist. However, atrophy
and fibrosis, serous cystadenoma and neuroendocrine tumors were more often
wrongly scored, in 63%, 100% and 25% respectively. CONCLUSION: FF-OCT could
distinguish normal pancreatic tissue from pathologic pancreatic tissue in both
processed as non-processed specimens using architectural features. The accuracy
in pancreatic ductal adenocarcinoma is promising and warrants further evaluation
using improved assessment criteria.
PMID- 28414766
TI - The metabolic basis of cognitive insight in psychosis: A positron emission
tomography study.
AB - : The purpose of this study was to investigate the relationship between cognitive
insight and cerebral metabolism in patients suffering from psychosis. The Beck
Cognitive Insight Scale (BCIS) was administered to 63 patients with psychosis
undergoing Positron Emission Tomography investigation. The sample was divided
into two groups considering the BCIS score. Data were analyzed using Statistical
Parametric Mapping. RESULTS: patients with low insight, compared to those with
high insight, showed decreased metabolism in the right fusiform gyrus, left
precuneus, superior temporal gyrus and insula bilaterally, as well as increased
metabolism in the left orbito-frontal gyrus (all p<0.005). Our results suggest
that reduced posterior (occipito-temporo-insulo-parietal) and increased anterior
(orbitofrontal) cerebral metabolism may sustain low cognitive insight in
psychosis.
PMID- 28414767
TI - The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA
interaction in vitro.
AB - The RNA-binding protein Hu antigen R (HuR) binds to AU-rich elements (ARE) in the
3'-untranslated region (UTR) of target mRNAs. The HuR-ARE interactions stabilize
many oncogenic mRNAs that play important roles in tumorigenesis. Thus, small
molecules that interfere with the HuR-ARE interaction could potentially inhibit
cancer cell growth and progression. Using a fluorescence polarization (FP)
competition assay, we identified the compound azaphilone-9 (AZA-9) derived from
the fungal natural product asperbenzaldehyde, binds to HuR and inhibits HuR-ARE
interaction (IC50 ~1.2 MUM). Results from surface plasmon resonance (SPR)
verified the direct binding of AZA-9 to HuR. NMR methods mapped the RNA-binding
interface of HuR and identified the involvement of critical RNA-binding residues
in binding of AZA-9. Computational docking was then used to propose a likely
binding site for AZA-9 in the RNA-binding cleft of HuR. Our results show that AZA
9 blocks key RNA-binding residues of HuR and disrupts HuR-RNA interactions in
vitro. This knowledge is needed in developing more potent AZA-9 derivatives that
could lead to new cancer therapy.
PMID- 28414768
TI - GPATCH3 negatively regulates RLR-mediated innate antiviral responses by
disrupting the assembly of VISA signalosome.
AB - Upon viral infection, retinoic acid-inducible gene I-like receptors (RLRs)
recognize viral RNA and trigger a series of signaling events, leading to the
induction of type I interferons (IFNs). These processes are delicately regulated
to prevent excessive and harmful immune responses. In this study, we identified G
patch domain-containing protein 3 (GPATCH3) as a negative regulator of RLR
mediated antiviral signaling pathways. Overexpression of GPATCH3 impaired RNA
virus- triggered induction of downstream antiviral genes, whereas its knockdown
had opposite effects and attenuated viral replication. In addition, GPATCH3
deficient cells had higher IFNB1 mRNA level compared with control cells after RNA
virus infection. Mechanistically, GPATCH3 was recruited to VISA in a viral
infection dependent manner and the assembly of VISA/TRAF6/TBK1 signalosome was
impaired in GPATCH3-overexpressing cells. In contrast, upon viral infection, the
recruitment of TRAF6 and TBK1 to VISA was enhanced in GPATCH3 deficient cells.
Taking together, our findings demonstrate that GPATCH3 interacts with VISA and
disrupts the assembly of virus-induced VISA signalosome therefore acts as a
negative regulator of RLR-mediated innate antiviral immune responses.
PMID- 28414769
TI - Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after
spinal cord contusion in rats for eventual intralesional implantation of
restorative materials.
AB - Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the
site of injury and adjacent segments. It is considered harmful because of its
potential to aggravate secondary injury, and to interfere with axonal
regeneration; it might also lead to an unfavorable environment for intralesional
implants. Removal of hemorrhagic necrosis has been attempted before with variable
results. The invasive nature of these procedures carries the risk of exacerbating
damage to the injured cord. The overall objective for this study was to test
several strategies for non-damaging removal of hemorrhagic necrosis and
characterize the resulting cavity looking for a space for future intralesional
therapeutic implants in rats with acute cord injury. Rats were subjected to
graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three
grades of myelotomy (extensive, medium sized, and small) were tested. Using the
small surgical approach to debridement, early and late effects of the
intervention were determined by histology and by analytical and behavioral
analysis. Appearance and capacity of the resulting cavity were characterized.
Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical
approaches to debridement. However, bleeding in spared cord tissue was excessive
after medium sized and extensive myelotomies but similar to control injured rats
after small cord surgery. Small surgical approach to debridement produced no
swelling nor acute inflammation changes, nor did it affect long-term spontaneous
locomotor recovery, but resulted in modest improvement of myelination in rats
subjected to both moderate and severe injuries. Cavity created after intervention
was filled with 10 to 15 MUL of hydrogel. In conclusion, by small surgical
approach to debridement, removal of hemorrhagic necrosis was achieved after acute
cord contusion thereby creating intramedullary spaces without further damaging
the injured spinal cord. Resulting cavities appear suitable for future
intralesional placement of pro-reparative cells or other regenerative
biomaterials in a clinically relevant model of spinal cord injury.
PMID- 28414770
TI - Correction: Efficient and robust differentiation of endothelial cells from human
induced pluripotent stem cells via lineage control with VEGF and cyclic AMP.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173271.].
PMID- 28414771
TI - Stability of gabapentin in extemporaneously compounded oral suspensions.
AB - This study reports the stability of extemporaneously prepared gabapentin oral
suspensions prepared at 100 mg/mL from bulk drug and capsules in either Oral Mix
or Oral Mix SF suspending vehicles. Suspensions were packaged in amber plastic
bottles and amber plastic syringes at 25 degrees C / 60%RH for up to 90 days.
Throughout the study period, the following tests were performed to evaluate the
stability of the preparations: organoleptic inspection to detect homogeneity,
color or odor changes; pH measurements; and gabapentin assay using a stability
indicating HPLC-UV method. As crystallization was observed at 5 degrees C,
storage at this temperature condition is not recommended. All preparations stored
at 25 degrees C / 60%RH remained stable for the whole study duration of 90 days.
PMID- 28414772
TI - The nanoparticle protein corona formed in human blood or human blood fractions.
AB - The protein corona formed around nanoparticles in protein-rich fluids plays an
important role for nanoparticle biocompatibility, as found in several studies
during the last decade. Biological fluids have complex compositions and the
molecular components interact and function together in intricate networks.
Therefore, the process to isolate blood or the preparation of blood derivatives
may lead to differences in the composition of the identified protein corona
around nanoparticles. Here, we show distinct differences in the protein corona
formed in whole blood, whole blood with EDTA, plasma, or serum. Furthermore, the
ratio between particle surface area to protein concentration influences the
detected corona. We also show that the nanoparticle size per se influences the
formed protein corona due to curvature effects. These results emphasize the need
of investigating the formation and biological importance of the protein corona in
the same environment as the nanoparticles are intended for or released into.
PMID- 28414773
TI - The importance of calcium in improving resistance of Daphnia to Microcystis.
AB - Changing environmental calcium (Ca) and rising cyanobacterial blooms in lake
habitats could strongly reduce Daphnia growth and survival. Here, we assessed the
effects of maternal Ca in Daphnia on transfer of resistance to their offspring
against Microcystis aeruginosa PCC7806 (M. aeruginosa). Laboratory microcosm
experiments were performed to examine effects in Daphnia carinata (D. carinata)
and Daphnia pulex (D. pulex), and that how Ca induce responses in their
offspring. The results showed that growth and survival were increased in
offspring from exposed Daphnia as compared to unexposed, when raised in high Ca
and increasing M. aeruginosa concentration. Among exposed Daphnia, offspring from
high Ca mothers, produced more neonates with large size and higher survival as
compared to offspring from low maternal Ca. Exposed D. carinata and D. pulex
offspring, when reared in Ca deficient medium and increasing M. aeruginosa
concentration, time to first brood increased, size become large and total
offspring decreased subsequently in three alternative broods in offspring from
low maternal Ca. In contrast, growth and reproduction in offspring from high Ca
exposed mothers were consistent in three alternative broods. Despite species
specific responses in growth, survival and variant life history traits in two
Daphnia species, our results not only show maternal induction in Daphnia but also
highlight that offspring response to M. aeruginosa varies with maternal Ca. This
study demonstrates that Ca have role in Daphnia maternal induction against
Microcystis, and recent Ca decline and increasing Microcystis concentration in
lakes may decrease Daphnia growth and survival. Our data provide insights into
the interactive effect of maternal Ca and Microcystis exposure on Daphnia and
their outcome on offspring life history traits and survival.
PMID- 28414776
TI - Correction: Malignant infarction of the middle cerebral artery in a porcine
model. A pilot study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172637.].
PMID- 28414774
TI - Mycobacterium marinum antagonistically induces an autophagic response while
repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.
AB - Autophagy is a eukaryotic catabolic process also participating in cell-autonomous
defence. Infected host cells generate double-membrane autophagosomes that mature
in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However,
several bacteria subvert autophagy and benefit from its machinery and functions.
Monitoring infection stages by genetics, pharmacology and microscopy, we
demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close
relative to M. tuberculosis, upregulates the transcription of autophagy genes,
and stimulates autophagosome formation and recruitment to the mycobacteria
containing vacuole (MCV) in the host model organism Dictyostelium.
Antagonistically, ESX-1 is also essential to block the autophagic flux and
deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize
to the MCV in an ESX-1-dependent manner, suggesting an important role in the
manipulation of autophagy by mycobacteria. Our findings suggest that the
infection by M. marinum activates an autophagic response that is simultaneously
repressed and exploited by the bacterium to support its survival inside the MCV.
PMID- 28414775
TI - Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of
syndromic X-linked intellectual disability.
AB - By searching a clinical database of over 60,000 individuals referred for array
based CNV analyses and online resources, we identified four males from three
families with intellectual disability, developmental delay, hypotonia, joint
hypermobility and relative macrocephaly who carried small, overlapping deletions
of Xp11.22. The maximum region of overlap between their deletions spanned ~430 kb
and included two pseudogenes, CENPVL1 and CENPVL2, whose functions are not known,
and two protein coding genes-the G1 to S phase transition 2 gene (GSPT2) and the
MAGE family member D1 gene (MAGED1). Deletions of this ~430 kb region have not
been previously implicated in human disease. Duplications of GSPT2 have been
documented in individuals with intellectual disability, but the phenotypic
consequences of a loss of GSPT2 function have not been elucidated in humans or
mouse models. Changes in MAGED1 have not been associated with intellectual
disability in humans, but loss of MAGED1 function is associated with
neurocognitive and neurobehavioral phenotypes in mice. In all cases, the Xp11.22
deletion was inherited from an unaffected mother. Studies performed on DNA from
one of these mothers did not show evidence of skewed X-inactivation. These
results suggest that deletions of an ~430 kb region on chromosome Xp11.22 that
encompass CENPVL1, CENPVL2, GSPT2 and MAGED1 cause a distinct X-linked syndrome
characterized by intellectual disability, developmental delay, hypotonia, joint
hypermobility and relative macrocephaly. Loss of GSPT2 and/or MAGED1 function may
contribute to the intellectual disability and developmental delay seen in males
with these deletions.
PMID- 28414777
TI - A unified approach for determining the ultimate strength of RC members subjected
to combined axial force, bending, shear and torsion.
AB - This paper uses experimental investigation and theoretical derivation to study
the unified failure mechanism and ultimate capacity model of reinforced concrete
(RC) members under combined axial, bending, shear and torsion loading. Fifteen RC
members are tested under different combinations of compressive axial force,
bending, shear and torsion using experimental equipment designed by the authors.
The failure mechanism and ultimate strength data for the four groups of tested RC
members under different combined loading conditions are investigated and
discussed in detail. The experimental research seeks to determine how the
ultimate strength of RC members changes with changing combined loads. According
to the experimental research, a unified theoretical model is established by
determining the shape of the warped failure surface, assuming an appropriate
stress distribution on the failure surface, and considering the equilibrium
conditions. This unified failure model can be reasonably and systematically
changed into well-known failure theories of concrete members under single or
combined loading. The unified calculation model could be easily used in design
applications with some assumptions and simplifications. Finally, the accuracy of
this theoretical unified model is verified by comparisons with experimental
results.
PMID- 28414778
TI - Correction: A novel hemagglutinin protein produced in bacteria protects chickens
against H5N1 highly pathogenic avian influenza viruses by inducing H5 subtype
specific neutralizing antibodies.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172008.].
PMID- 28414779
TI - Seed germination in relation to the invasiveness in spiny amaranth and edible
amaranth in Xishuangbanna, SW China.
AB - Both spiny and edible amaranths (Amaranthus spinosus and A. tricolor) are exotic
annuals in China that produce numerous small seeds every year. Spiny amaranth has
become a successful invader and a troublesome weed in Xishuangbanna, but edible
amaranth has not, although it is widely grown as a vegetable there. As seed
germination is one of the most important life-stages contributing to the ability
of a plant to become invasive, we conducted experiments to compare the effects of
high temperature and water stress on seed germination in two varieties each of
spiny amaranth and edible amaranth. Overall, the seeds of both amaranth species
exhibited adaptation to high temperature and water stress, including tolerance to
ground temperatures of 70 degrees C for air-dried seeds, which is consistent with
their behavior in their native ranges in the tropics. As expected, the invasive
spiny amaranth seeds exhibited higher tolerance to both continuous and daily
periodic high-temperature treatment at 45 degrees C, and to imbibition
desiccation treatment, compared to edible amaranth seeds. Unexpectedly, edible
amaranth seeds exhibited higher germination at extreme temperatures (10 degrees
C, 15 degrees C, and 40 degrees C), and at lower water potential (below -0.6
MPa). It is likely that cultivation of edible amaranth has selected seed traits
that include rapid germination and germination under stressful conditions, either
of which, under natural conditions, may result in the death of most germinating
edible amaranth seeds and prevent them from becoming invasive weeds in
Xishuangbanna. This study suggests that rapid germination and high germination
under stress conditions-excellent seed traits for crops and for many invasive
species-might be a disadvantage under natural conditions if these traits are
asynchronous with natural local conditions that support successful germination.
PMID- 28414781
TI - Voice disorder in systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a chronic disease characterized by
progressive tissue damage. In recent decades, novel treatments have greatly
extended the life span of SLE patients. This creates a high demand for
identifying the overarching symptoms associated with SLE and developing therapies
that improve their life quality under chronic care. We hypothesized that SLE
patients would present dysphonic symptoms. Given that voice disorders can reduce
life quality, identifying a potential SLE-related dysphonia could be relevant for
the appraisal and management of this disease. We measured objective vocal
parameters and perceived vocal quality with the GRBAS (Grade, Roughness,
Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched
healthy controls. SLE patients also filled a questionnaire reporting perceived
vocal deficits. SLE patients had significantly lower vocal intensity and
harmonics to noise ratio, as well as increased jitter and shimmer. All subjective
parameters of the GRBAS scale were significantly abnormal in SLE patients.
Additionally, the vast majority of SLE patients (29/36) reported at least one
perceived vocal deficit, with the most prevalent deficits being vocal fatigue
(19/36) and hoarseness (17/36). Self-reported voice deficits were highly
correlated with altered GRBAS scores. Additionally, tissue damage scores in
different organ systems correlated with dysphonic symptoms, suggesting that some
features of SLE-related dysphonia are due to tissue damage. Our results show that
a large fraction of SLE patients suffers from perceivable dysphonia and may
benefit from voice therapy in order to improve quality of life.
PMID- 28414780
TI - Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid
tissue.
AB - BACKGROUND: The implementation of successful strategies to achieve an HIV cure
has become a priority in HIV research. However, the current location and size of
HIV reservoirs is still unknown since there are limited tools to evaluate HIV
latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As
reported in the so called "Boston Patients", despite undetectable levels of
proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months
after ART interruption. This fact might imply that current methods are not
sensitive enough to detect residual reservoirs. Showing that, it is imperative to
improve the detection and quantification of HIV-1 reservoir in tissue samples.
Herein, we propose a novel non-enzymatic protocol for purification of Lamina
Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA)
quantification by droplet digital PCR (ddPCR) to improve the sensitivity and
accuracy of viral reservoir measurements (LPL-vDNA assay). METHODS: Endoscopic
ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We
performed a DTT/EDTA-based treatment for epithelial layer removal followed by non
enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP).
CD45+ cells were subsequently purified by flow sorting and vDNA was determined by
ddPCR. RESULTS: vDNA quantification levels were significantly higher in purified
LPLs (CD45+) than in bulk LPs (p<0.01). The levels of vDNA were higher in ileum
samples than in concurrent PBMC from the same individuals (p = 0.002). As a
result of the increased sensitivity of this purification method, the Poisson 95%
confidence intervals of the vDNA quantification data from LPLs were narrower than
that from bulk LPs. Of note, vDNA was unambiguously quantified above the
detection limit in 100% of LPL samples, while only in 58% of bulk LPs.
CONCLUSION: We propose an innovative combined protocol for a more sensitive
detection of the HIV reservoir in gut-associated viral sanctuaries, which might
be used to evaluate any proposed eradication strategy.
PMID- 28414782
TI - Identification of the chain-dispersing peptidoglycan hydrolase LytB of
Streptococcus gordonii.
AB - Bacterial cell division ends with the separation of the daughter cells, a process
that requires peptidoglycan hydrolases (PGHs). Bacteria lacking cell separating
PGHs are impaired in cell separation with the formation of long chains or
clusters. We identified a gene in Streptococcus gordonii encoding for a putative
glucosaminidase (lytB). The lytB isogenic mutant grew in long bacterial chains
and resulted in impaired biofilm formation. Purified recombinant LytB showed a
murolytic activity on Micrococcus lysodeikticus cell suspension and was able to
disperse the long chains of the mutant, restoring the wild type diplococci/short
chain phenotype. LytB protein was localized only in culture supernatant cell
fraction of S. gordonii, and co-cultures of wild type and lytB mutant showed a
significant reduction of bacterial chain length, indicating that LytB is a
secreted enzyme. Our results demonstrate that LytB is a secreted peptidoglycan
hydrolase required for S. gordonii cell separation.
PMID- 28414784
TI - Savanna elephant numbers are only a quarter of their expected values.
AB - Savannas once constituted the range of many species that human encroachment has
now reduced to a fraction of their former distribution. Many survive only in
protected areas. Poaching reduces the savanna elephant, even where protected,
likely to the detriment of savanna ecosystems. While resources go into estimating
elephant populations, an ecological benchmark by which to assess counts is
lacking. Knowing how many elephants there are and how many poachers kill is
important, but on their own, such data lack context. We collated savanna elephant
count data from 73 protected areas across the continent estimated to hold ~50% of
Africa's elephants and extracted densities from 18 broadly stable population time
series. We modeled these densities using primary productivity, water
availability, and an index of poaching as predictors. We then used the model to
predict stable densities given current conditions and poaching for all 73
populations. Next, to generate ecological benchmarks, we predicted such densities
for a scenario of zero poaching. Where historical data are available, they
corroborate or exceed benchmarks. According to recent counts, collectively, the
73 savanna elephant populations are at 75% of the size predicted based on current
conditions and poaching levels. However, populations are at <25% of ecological
benchmarks given a scenario of zero poaching (~967,000)-a total deficit of
~730,000 elephants. Populations in 30% of the 73 protected areas were <5% of
their benchmarks, and the median current density as a percentage of ecological
benchmark across protected areas was just 13%. The ecological context provided by
these benchmark values, in conjunction with ongoing census projects, allow
efficient targeting of conservation efforts.
PMID- 28414783
TI - Acceptability and feasibility of early infant male circumcision for HIV
prevention in Malawi.
AB - BACKGROUND: Voluntary medical male circumcision (VMMC) has been successfully
implemented in 14 countries as an additional HIV prevention intervention. As VMMC
programs mature in most countries, the focus is now on how to sustain the HIV
prevention gains realised from VMMC. As part of preparations for the
sustainability phase, countries are either piloting or preparing to pilot early
infant male circumcision (EIMC). This qualitative study explored the
acceptability and feasibility of EIMC in Malawi in order to inform pilot
implementation. METHODS: In 2016, 23 focus group discussions were held across
Malawi with participants from several ethnicities and religions/faiths.
Additionally, 21 key informant interviews were held with traditional and
religious leaders, traditional circumcisers (ngalibas), policy-makers, programme
managers and health-care workers. Audio recordings were transcribed, translated
into English (where necessary), and thematically coded using NVivo 10. RESULTS:
Discussions highlighted the socio-cultural significance of MC in Malawi.
Knowledge or experience of EIMC was poor although acceptability was high among
most ethnic/religious groups and key informants. Participants identified EIMC's
comparative HIV benefits although a few health-care workers expressed scepticism.
All participants said EIMC should be offered within a clinical setting. In
addition to fathers, maternal uncles and traditional leaders were deemed key
decision-makers. Potential barriers to EIMC included concerns about procedure
safety as well as cultural considerations. Key informants felt it was feasible to
offer EIMC in Malawi. Participants' recommendations, including phased
implementation, engagement of traditional leaders, use of external mobilisers and
initially reaching out to influential parents, will be taken into account when
designing a pilot EIMC program. CONCLUSIONS: EIMC is potentially an acceptable
and feasible HIV prevention intervention for most ethnic/religious groups in
Malawi if wide-ranging, culturally appropriate demand-creation activities are
developed, piloted, evaluated and appropriately implemented.
PMID- 28414785
TI - The Epstein-Barr virus miR-BHRF1-1 targets RNF4 during productive infection to
promote the accumulation of SUMO conjugates and the release of infectious virus.
AB - Post-translational modification by the Small Ubiquitin-like Modifier (SUMO)
regulates a variety of cellular functions, and is hijacked by viruses to remodel
the host cell during latent and productive infection. Here we have monitored the
activity of the SUMO conjugation machinery in cells productively infected with
Epstein-Barr virus (EBV). We found that SUMO2/3 conjugates accumulate during the
late phase of the productive virus cycle, and identified several viral proteins
as bone fide SUMOylation substrates. Analysis of the mechanism involved in the
accumulation of SUMOylated proteins revealed upregulation of several components
of the SUMO-conjugation machinery and post-transcriptional downregulation of the
SUMO-targeted ubiquitin ligase RNF4. The latter effect was mediated by selective
inhibition of RNF4 protein expression by the viral miR-BHRF1-1. Reconstitution of
RNF4 in cells expressing an inducible miR-BHRF1-1 sponge or a miR-BHRF1-1
resistant RNF4 was associated with reduced levels of early and late viral
proteins and impaired virus release. These findings illustrate a novel strategy
for viral interference with the SUMO pathway, and identify the EBV miR-BHRF1-1
and the cellular RNF4 as regulators of the productive virus cycle.
PMID- 28414786
TI - The Model for End-stage Liver Disease (MELD) as a predictor of short-term
mortality in Staphylococcus aureus bloodstream infection: A single-centre
observational study.
AB - BACKGROUND: Automated laboratory-based prediction models may support clinical
decisions in Staphylococcus aureus bloodstream infections (BSIs), which carry a
particularly high mortality. Small studies indicated that the laboratory-based
Model for End-stage Liver Disease (MELD) score is a risk factor for mortality in
critically ill patients with infections. For S. aureus BSIs, we therefore aimed
to assess a potential association of the MELD score with mortality. METHODS: In
this single-centre observational study, all consecutive patients with a first
episode of methicillin-susceptible S. aureus BSI occurring between 2001 and 2013
were eligible. Relevant patient data were retrieved from our prospective in-house
BSI database. We assessed the association of the MELD score at day of BSI onset
(range +/- two days) with 30-day all-cause mortality using uni- and multivariable
logistic regression analysis. RESULTS: 561 patients were included in the final
analysis. The MELD score at BSI onset was associated with 30-day mortality in S.
aureus BSIs (odds ratio per 1-point increase, 1.06; 95% confidence interval, 1.03
1.09; P < 0.001). After adjustment for relevant patient and infection
characteristics, an increased MELD score remained a predictor of 30-day mortality
(adjusted odds ratio per 1-point increase, 1.05; 95% confidence interval, 1.01
1.08; P = 0.005). CONCLUSIONS: In our study population, the MELD score at BSI
onset was an independent predictor of mortality in S. aureus BSIs. We therefore
suggest to prospectively validate the MELD score as part of clinical decision
support systems in inpatients with suspected or confirmed BSI.
PMID- 28414787
TI - Water abstraction affects abundance, size-structure and growth of two threatened
cyprinid fishes.
AB - Hydrologic alteration is a major threat to freshwater biota, and particularly
fish, in many river courses around the world. We analyzed and compared the
effects of water abstraction on two threatened cyprinid fishes of contrasting
ecology (the Mediterranean barbel Barbus meridionalis and the Catalan chub
Squalius laietanus) in a Mediterranean stream. We compared abundance, size
structure, growth, and condition of both species across perennial and
artificially intermittent reaches affected by water abstraction. Both species
were less abundant, had scarce large individuals, and displayed slower growth
rates (length-at-age) in intermittent reaches, showing clear detrimental effects
of water diversion. Mixed-effect models of scale increments showed variation
among individuals and among sites, years and age classes for both species. The
larger-sized, water-column species (chub) disappeared or was rare in many
intermittent reaches. The barbel present in intermittent reaches showed better
somatic condition than in sites with permanent flow, perhaps due to reduced
competition after rewetting or colonization by better fitted individuals. This
benthic, rheophilic species seems more resilient to moderate water abstraction
than chub. Many effects of water flow intermittency were only detected on fish
life-history traits when accounting for natural, often non-linear, variation,
along upstream-downstream gradients. Our results suggest that abundance was the
strongest indicator of effects of water abstraction on fish populations, whereas
condition was a more labile trait, rapidly recovering from anthropogenic
disturbance.
PMID- 28414788
TI - Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a
higher risk of miscarriage: A systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the relationship between subclinical hypothyroidism (SCH)
and the risk of miscarriage before 20 weeks of pregnancy. METHODS: Literature
databases were searched, including the PubMed, Web of Science, Embase and
Cochrane databases, from January 1, 1980, to December 31, 2015. The following
search terms were used: subclinical hypothyroidism, hypothyroidism, thyroid
dysfunction, thyroid hypofunction, subclinical thyroid disease, thyroid
dysfunction, pregnancy loss, abortion and miscarriage. Studies comparing the
prevalence of miscarriage in pregnant women with SCH with those who were
euthyroid were selected. From the studies matched, the relative risk (RR) and
corresponding 95% confidence interval (95% CI) were calculated to yield outcomes.
All the statistical analyses were performed using Review Manager (Revman) Version
5.3 and Stata Version 12.0 software. The publication bias of the studies was
assessed by forest plot and Begg's test, while the stability of the results was
evaluated by sensitivity analysis. RESULTS: Nine articles satisfying the
inclusion criteria were analysed. Compared to euthyroid pregnant women, patients
with non-treated SCH had a higher prevalence of miscarriage (RR = 1.90, 95%
CI1.59-2.27, P<0.01). Additionally, SCH patients in the international diagnostic
criteria group were more likely to suffer miscarriages than those in the ATA
diagnostic criteria group (chi2 = 11.493, P<0.01). Moreover, there was no
difference between patients with treated SCH and euthyroid women (RR = 1.14, 95%
CI0.82-1.58, P = 0.43). Compared to isolated SCH women, the miscarriage risk of
SCH patients with thyroid autoimmunity (TAI) was obviously higher (RR = 2.47, 95%
CI1.77-3.45, P<0.01), and isolated SCH patients also had a higher prevalence of
miscarriages than euthyroid women (RR = 1.45, 95% CI1.07-1.96, P = 0.02).A
heterogeneity test, forest plot and Begg's test suggested that there was no
significant heterogeneity or publication bias among the included articles, while
the result of sensitivity analysis showed that our study exhibited high
stability. CONCLUSION: SCH is a risk factor for miscarriage in women before 20
weeks of pregnancy, and early treatments can reduce the miscarriage rate.
Regardless of the diagnostic criteria used, the miscarriage rate increased as
long as a pregnant woman was confirmed to have SCH. The results show that the
omission diagnostic rate may increase when the ATA diagnostic criteria are used.
In addition, SCH patients with TAI have a higher prevalence of miscarriage, while
isolated SCH patients also have a higher miscarriage rate than euthyroid women.
Thus, we recommend early treatments to avoid adverse pregnancy outcomes and
complications.
PMID- 28414789
TI - Effect of pH on temperature controlled degradation of reactive oxygen species,
heat shock protein expression, and mucosal immunity in the sea cucumber
Isostichopus badionotus.
AB - This study evaluated the effect of pH on the activity of antioxidant and immune
enzymes in the sea cucumber Isostichopus badionotus exposed to different
temperatures. The organisms (530 +/-110 g) were exposed to 16, 20, 24, 28, 30, 34
and 36 degrees C for 6 h to evaluate thermal limits at two water pH values
(treatment = 7.70; control = 8.17). For the thermal tolerance experiment, the
organisms were exposed to sublethal temperature of 34 degrees C for 3, 6, 12, 24,
and 48 h. I. badionotus showed signs of thermal stress by synthesizing heat shock
protein 70 (hsp70) at the cold (16 degrees C) and warm thermal limits (34 degrees
C). The glutathione peroxidase (GPx) showed a negative correlation with
superoxide dismutase (SOD) activity in modulating the effect of oxidative stress
at different temperature levels. Specifically, GPx activity was maximal at the
extremes of the cold and warm temperatures (16, 20, and 36 degrees C) tested,
while contrarily, the SOD activity increased significantly in the narrow range of
temperature between 28 and 30 degrees C, as a part of a reaction to offset
oxidative damage. The effect of pH on the expression of hsp70 was not
significant, whereas the antioxidant enzymes activity was stimulated at pH 7.70.
Mucosal immunity, evidenced by the activation of the phenoloxidase (PO) system,
increased above the basal level at pH 7.70 and at 28, 30, and 34 degrees C.
Independent of pH, the temperature of 34 degrees C was identified as the 12 h
sublethal upper limit for I. badionotus.
PMID- 28414790
TI - Correction: Influence of intraocular lens subsurface nanoglistenings on
functional visual acuity.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173574.].
PMID- 28414791
TI - Speciation in progress? A phylogeographic study among populations of Hemitrichia
serpula (Myxomycetes).
AB - Myxomycetes (plasmodial slime molds, Amoebozoa) are often perceived as widely
distributed, confounding to the "everything is everywhere" hypothesis. To test if
gene flow within these spore-dispersed protists is restricted by geographical
barriers, we chose the widespread but morphologically unmistakable species
Hemitrichia serpula for a phylogeographic study. Partial sequences from nuclear
ribosomal RNA genes (SSU) revealed 40 ribotypes among 135 specimens, belonging to
three major clades. Each clade is dominated by specimens from a certain region
and by one of two morphological varieties which can be differentiated by SEM
micrographs. Partial sequences of the protein elongation factor 1 alpha (EF1A)
showed each clade to possess a unique combination of SSU and EF1A genotypes. This
pattern is best explained assuming the existence of several putative biospecies
dominating in a particular geographical region. However, occasional mismatches
between molecular data and morphological characters, but as well heterogeneous
SSU and heterozygous EF1A sequences, point to ongoing speciation. Environmental
niche models suggest that the putative biospecies are rather restricted by
geographical barriers than by macroecological conditions. Like other protists,
myxomycetes seem to follow the moderate endemicity hypothesis and are in active
speciation, which is most likely shaped by limited gene flow and reproductive
isolation.
PMID- 28414792
TI - Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of
Niemann-Pick Disease type C1.
AB - 2-Hydroxypropyl-beta-cyclodextrin (HPbetaCD) has gained recent attention as a
potential therapeutic intervention in the treatment of the rare autosomal
recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type
C1 (NPC1). Notably, HPbetaCD formulations are not comprised of a single molecular
species, but instead are complex mixtures of species with differing degrees of
hydroxypropylation of the cyclodextrin ring. The degree of substitution is a
critical aspect of the complex mixture as it influences binding to other
molecules and thus could potentially modulate biological effects. VTS-270
(Kleptose HPB) and Trappsol(r) CycloTM are HPbetaCD products under investigation
as novel treatments for NPC1. The purpose of the present work is to compare these
two different products; analyses were based on ion distribution and abundance
profiles using mass spectrometry methodology as a means for assessing key
molecular distinctions between products. The method incorporated electrospray
ionization and analysis with a linear low-field ion mobility quadrupole time-of
flight instrument. We observed that the number of hydroxypropyl groups (the
degrees of substitution) are substantially different between the two products and
greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are
ammonium adducts. Isotope clusters for each of the major ions show doubly charged
homodimers of the ammonium adducts. In addition, both products show doubly
charged homodimers from adduction of both a proton and ammonium. Doubly charged
heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS
270. Based on the analytical differences observed between VTS-270 and Trappsol
Cyclo with respect to the degree of substitution, the composition and fingerprint
of the complex mixture, and the impurity profiles, these products cannot be
considered to be the same; the potential biological and clinical implications of
these differences are not presently known.
PMID- 28414793
TI - Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt
signaling pathway.
AB - Radiotherapy is a powerful tool in the treatment of cancer that has the advantage
of preserving normal tissues. However, tumor radioresistance currently remains a
major impediment to effective RT. Thus, exploring effective radiation sensitizers
is urgently needed. In this study, we have shown that diosmetin, the aglycone of
the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs,
has a promising effect on radiotherapy sensitization. In our results, DIO could
induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant
A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA
damage repair by inhibiting the activated Akt signaling pathway. The combination
of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked
A549/IR cancer cell proliferation. In summary, these observations suggest that
the natural compound DIO could act as a potential drug for the treatment of
radioresistant lung cancer cells.
PMID- 28414794
TI - Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced
acute ileitis in mice harboring a human gut microbiota.
AB - BACKGROUND: Within seven days following peroral high dose infection with
Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis
due to an underlying T helper cell (Th) -1 type immunopathology. We here
addressed whether mice harboring a human intestinal microbiota developed
intestinal, extra-intestinal and systemic sequelae upon ileitis induction.
METHODOLOGY/PRINCIPAL FINDINGS: Secondary abiotic mice were generated by broad
spectrum antibiotic treatment and associated with a complex human intestinal
microbiota following peroral fecal microbiota transplantation. Within three weeks
the human microbiota had stably established in the murine intestinal tract as
assessed by quantitative cultural and culture-independent (i.e. molecular 16S
rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii
strain ME49 by gavage human microbiota associated (hma) mice displayed severe
clinical, macroscopic and microscopic sequelae indicating acute ileitis. In
diseased hma mice increased numbers of innate and adaptive immune cells within
the ileal mucosa and lamina propria and elevated intestinal secretion of pro
inflammatory mediators including IFN-gamma, IL-12 and nitric oxide could be
observed at day 7 p.i. Ileitis development was accompanied by substantial shifts
in intestinal microbiota composition of hma mice characterized by elevated total
bacterial loads and increased numbers of intestinal Gram-negative commensals such
as enterobacteria and Bacteroides / Prevotella species overgrowing the small and
large intestinal lumen. Furthermore, viable bacteria translocated from the
inflamed ileum to extra-intestinal including systemic compartments. Notably, pro
inflammatory immune responses were not restricted to the intestinal tract as
indicated by increased pro-inflammatory cytokine secretion in extra-intestinal
(i.e. liver and kidney) and systemic compartments including spleen and serum.
CONCLUSION/SIGNIFICANCE: With respect to the intestinal microbiota composition
"humanized" mice display acute ileitis following peroral high dose T. gondii
infection. Thus, hma mice constitute a suitable model to further dissect the
interactions between pathogens, human microbiota and vertebrate host immunity
during acute intestinal inflammation.
PMID- 28414795
TI - Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1.
AB - Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at
gene promoter regions critically regulates gene expression. Key developmental
genes tend to exhibit changes in histone modification patterns from the
H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using
comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow
derived macrophages (BMMs) and mature osteoclasts, we found that cell surface
adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T
cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent
pattern in osteoclasts. Cadm1 expression was upregulated in BMMs by receptor
activator of nuclear factor kappa B ligand (RANKL), and blocked by a
calcineurin/NFATc1 inhibitor, FK506. Cadm1-deficient mice exhibited significantly
reduced bone mass compared with wild-type mice, which was due to the increased
osteoclast differentiation, survival and bone-resorbing activity in Cadm1
deficient osteoclasts. These results suggest that Cadm1 is a direct target of
NFATc1, which is induced by RANKL through epigenetic modification, and regulates
osteoclastic bone resorption in a negative feedback manner.
PMID- 28414796
TI - Post-ischemic stroke rehabilitation is associated with a higher risk of fractures
in older women: A population-based cohort study.
AB - BACKGROUND: Rehabilitation can improve physical activity after stroke. However,
patients may be more prone to falls and fractures because of balance and gait
deficits. Few reports have studied the relationship between rehabilitation and
subsequent fractures after ischemic stroke. OBJECTIVE: To investigate whether
post-stroke rehabilitation affects fracture risk. METHODS: We conducted a
population-based retrospective cohort study based on the Taiwan National Health
Insurance Research Database. Patients with a newly diagnosed ischemic stroke
between 2000 and 2012 were included. After propensity score matching, a total of
8,384 patients were enrolled. Half of the patients (4,192) received post-stroke
rehabilitation within 1 month; the other half did not receive any post-stroke
rehabilitation. Cox proportional hazards regression model was used to calculate
hazard ratios (HRs) for fractures among patients with and without rehabilitation
within 1 year after ischemic stroke. Patients were further stratified by sex and
age (20-64 and >=65 years). RESULTS: Patients receiving post-stroke
rehabilitation had a higher incidence of fracture (6.2 per 100 person-years) than
those who did not (4.1 per 100 person-years) after adjustment for
sociodemographic and coexisting medical conditions [HR = 1.53, 95% confidence
interval (CI) = 1.25-1.87, p < 0.001]. The analyses performed after stratifying
for sex and age showed that only older women undergoing rehabilitation had a
significantly higher risk of fracture (HR = 1.62, 95% CI = 1.21-2.17, p = 0.001).
CONCLUSION: Rehabilitation after ischemic stroke is associated with an increased
fracture risk in older women.
PMID- 28414798
TI - Correction: Enteric Neuronal Damage, Intramuscular Denervation and Smooth Muscle
Phenotype Changes as Mechanisms of Chagasic Megacolon: Evidence from a Long-Term
Murine Model of Tripanosoma cruzi Infection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0153038.].
PMID- 28414797
TI - BIG1 is required for the survival of deep layer neurons, neuronal polarity, and
the formation of axonal tracts between the thalamus and neocortex in developing
brain.
AB - BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1
gene, is one of candidate genes for epileptic encephalopathy. To know the
involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice
and found that BIG1 regulates neurite outgrowth and brain development in vitro
and in vivo. The loss of BIG1 decreased the size of the neocortex and
hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the
interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons
showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed
from the piriform cortex (PIR), peaked in the neocortex, and then progressed into
the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL)
and DL order in the neocortex was maintained in BIG1-deficient mice, but the
excitatory neurons tended to accumulate before their destination layers. Further
pulse-chase migration assay showed that the migration defect was non-cell
autonomous and secondary to the progression of apoptosis into the BIG1-deficient
neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection
of corticothalamic axons from the primary somatosensory cortex (S1) into the
dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable
to cross the diencephalon-telencephalon boundary (DTB). In vitro, BIG1-deficient
neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also
hypersensitive to low dose glutamate (5 MUM), and died via apoptosis. This study
showed the role of BIG1 in the survival of DL neurons in developing embryonic
brain and in the generation of neuronal polarity.
PMID- 28414799
TI - Comprehensive evaluation of ten deformable image registration algorithms for
contour propagation between CT and cone-beam CT images in adaptive head & neck
radiotherapy.
AB - Deformable image registration (DIR) is a critical technic in adaptive
radiotherapy (ART) for propagating contours between planning computerized
tomography (CT) images and treatment CT/cone-beam CT (CBCT) images to account for
organ deformation for treatment re-planning. To validate the ability and accuracy
of DIR algorithms in organ at risk (OAR) contour mapping, ten intensity-based DIR
strategies, which were classified into four categories-optical flow-based, demons
based, level-set-based and spline-based-were tested on planning CT and fractional
CBCT images acquired from twenty-one head & neck (H&N) cancer patients who
underwent 6~7-week intensity-modulated radiation therapy (IMRT). Three similarity
metrics, i.e., the Dice similarity coefficient (DSC), the percentage error (PE)
and the Hausdorff distance (HD), were employed to measure the agreement between
the propagated contours and the physician-delineated ground truths of four OARs,
including the vertebra (VTB), the vertebral foramen (VF), the parotid gland (PG)
and the submandibular gland (SMG). It was found that the evaluated DIRs in this
work did not necessarily outperform rigid registration. DIR performed better for
bony structures than soft-tissue organs, and the DIR performance tended to vary
for different ROIs with different degrees of deformation as the treatment
proceeded. Generally, the optical flow-based DIR performed best, while the demons
based DIR usually ranked last except for a modified demons-based DISC used for CT
CBCT DIR. These experimental results suggest that the choice of a specific DIR
algorithm depends on the image modality, anatomic site, magnitude of deformation
and application. Therefore, careful examinations and modifications are required
before accepting the auto-propagated contours, especially for automatic re
planning ART systems.
PMID- 28414800
TI - Semantic prioritization of novel causative genomic variants.
AB - Discriminating the causative disease variant(s) for individuals with inherited or
de novo mutations presents one of the main challenges faced by the clinical
genetics community today. Computational approaches for variant prioritization
include machine learning methods utilizing a large number of features, including
molecular information, interaction networks, or phenotypes. Here, we demonstrate
the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies
and automated reasoning over genotype-phenotype relations to filter and
prioritize variants in whole exome and whole genome sequencing datasets. We
demonstrate the performance of PVP in identifying causative variants on a large
number of synthetic whole exome and whole genome sequences, covering a wide range
of diseases and syndromes. In a retrospective study, we further illustrate the
application of PVP for the interpretation of whole exome sequencing data in
patients suffering from congenital hypothyroidism. We find that PVP accurately
identifies causative variants in whole exome and whole genome sequencing datasets
and provides a powerful resource for the discovery of causal variants.
PMID- 28414801
TI - Probabilistic fluorescence-based synapse detection.
AB - Deeper exploration of the brain's vast synaptic networks will require new tools
for high-throughput structural and molecular profiling of the diverse populations
of synapses that compose those networks. Fluorescence microscopy (FM) and
electron microscopy (EM) offer complementary advantages and disadvantages for
single-synapse analysis. FM combines exquisite molecular discrimination
capacities with high speed and low cost, but rigorous discrimination between
synaptic and non-synaptic fluorescence signals is challenging. In contrast, EM
remains the gold standard for reliable identification of a synapse, but offers
only limited molecular discrimination and is slow and costly. To develop and test
single-synapse image analysis methods, we have used datasets from conjugate array
tomography (cAT), which provides voxel-conjugate FM and EM (annotated) images of
the same individual synapses. We report a novel unsupervised probabilistic method
for detection of synapses from multiplex FM (muxFM) image data, and evaluate this
method both by comparison to EM gold standard annotated data and by examining its
capacity to reproduce known important features of cortical synapse distributions.
The proposed probabilistic model-based synapse detector accepts molecular
morphological synapse models as user queries, and delivers a volumetric map of
the probability that each voxel represents part of a synapse. Taking human
annotation of cAT EM data as ground truth, we show that our algorithm detects
synapses from muxFM data alone as successfully as human annotators seeing only
the muxFM data, and accurately reproduces known architectural features of
cortical synapse distributions. This approach opens the door to data-driven
discovery of new synapse types and their density. We suggest that our
probabilistic synapse detector will also be useful for analysis of standard
confocal and super-resolution FM images, where EM cross-validation is not
practical.
PMID- 28414802
TI - Neuronal cell fate specification by the molecular convergence of different spatio
temporal cues on a common initiator terminal selector gene.
AB - The extensive genetic regulatory flows underlying specification of different
neuronal subtypes are not well understood at the molecular level. The Nplp1
neuropeptide neurons in the developing Drosophila nerve cord belong to two sub
classes; Tv1 and dAp neurons, generated by two distinct progenitors. Nplp1
neurons are specified by spatial cues; the Hox homeotic network and GATA factor
grn, and temporal cues; the hb -> Kr -> Pdm -> cas -> grh temporal cascade. These
spatio-temporal cues combine into two distinct codes; one for Tv1 and one for dAp
neurons that activate a common terminal selector feedforward cascade of col ->
ap/eya -> dimm -> Nplp1. Here, we molecularly decode the specification of Nplp1
neurons, and find that the cis-regulatory organization of col functions as an
integratory node for the different spatio-temporal combinatorial codes. These
findings may provide a logical framework for addressing spatio-temporal control
of neuronal sub-type specification in other systems.
PMID- 28414803
TI - New metric for optimizing Continuous Loop Averaging Deconvolution (CLAD)
sequences under the 1/f noise model.
AB - Continuous loop averaging deconvolution (CLAD) is one of the proven methods for
recovering transient auditory evoked potentials (AEPs) in rapid stimulation
paradigms, which requires an elaborated stimulus sequence design to attenuate
impacts from noise in data. The present study aimed to develop a new metric in
gauging a CLAD sequence in terms of noise gain factor (NGF), which has been
proposed previously but with less effectiveness in the presence of pink (1/f)
noise. We derived the new metric by explicitly introducing the 1/f model into the
proposed time-continuous sequence. We selected several representative CLAD
sequences to test their noise property on typical EEG recordings, as well as on
five real CLAD electroencephalogram (EEG) recordings to retrieve the middle
latency responses. We also demonstrated the merit of the new metric in generating
and quantifying optimized sequences using a classic genetic algorithm. The new
metric shows evident improvements in measuring actual noise gains at different
frequencies, and better performance than the original NGF in various aspects. The
new metric is a generalized NGF measurement that can better quantify the
performance of a CLAD sequence, and provide a more efficient mean of generating
CLAD sequences via the incorporation with optimization algorithms. The present
study can facilitate the specific application of CLAD paradigm with desired
sequences in the clinic.
PMID- 28414804
TI - Cyclosporine A alters expression of renal microRNAs: New insights into
calcineurin inhibitor nephrotoxicity.
AB - Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ
transplantation. However, non-immune effects of the calcineurin inhibitor, such
as cyclosporine A (CsA), have significantly hindered their use. Specifically,
nephrotoxicity, which is associated with tubulointerstitial fibrosis,
inflammation, and podocyte damage, affects up to half of all transplant patients.
Calcineurin is involved in many aspects of kidney development and function;
therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully
understood. MicroRNAs are short non-coding RNAs that regulate protein-coding RNA
expression through post-translational repression of target messenger RNAs.
MicroRNA dysregulation is known to be involved in kidney diseases including
fibrosis. In this study, we compared the renal microRNA expression profiles
between mice that received CsA (20 mg/kg) or vehicle daily for six weeks. The
results demonstrate that CsA induces significant changes in renal microRNA
expression profile. We used combined criteria of False Discovery Rate (<=0.1),
fold change (>=2) and median signal strength (>=50) and identified 76
differencially expressed microRNAs. This approach identified microRNAs previously
linked to renal fibrosis that includes let-7d, miR-21, miR-29, miR-30, miR-130,
miR-192, and miR-200 as well as microRNAs that have not been reported to be
related to nephrotoxicity or immunosuppression. Pathway analysis of microRNA/mRNA
changes highlights the Wnt, TGF-beta, mTOR, and VEGF pathways. The mRNA
expression profiles were compared in the same samples. The change of mRNA and
microRNA profiles showed close correlations. To validate that the observed
microRNA and mRNA expression level changes in mice kidney tissue were directly
related to CsA treatment, the expression change induced by CsA treatment of three
microRNAs (miR-21, miR-186, and miR-709) and three mRNAs (BMPR1a, SMURF1 and
SMAD7) were compared in HEK293 cell line. A similar trend of expression level
change was induced by CsA treatment in all selected microRNAs and mRNAs in the in
vitro cell model. These data provide a roadmap for future work to study the role
of the known and novel candidate microRNAs in the mechanism of nephrotoxicity and
their further therapeutic potential.
PMID- 28414805
TI - Measurements of the parapapillary atrophy zones in en face optical coherence
tomography images.
AB - OBJECTIVE: To measure the parapapillary atrophy (PPA) area in en face images
obtained with swept-source optical coherence tomography (SS-OCT), and to evaluate
its relationship to glaucoma, myopia, and age in non-highly myopic subjects.
DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Fifty eyes of 30
subjects with open-angle glaucoma (G group) and forty-three eyes of 26 healthy
control subjects (C group). Eyes with high myopia (spherical equivalent
refractive error <= -8 diopters or axial length >= 26.5 mm) were excluded.
METHODS: Mean age +/- standard deviation was 59.9 +/- 12.4 years. The beta zone
and the gamma zone PPA areas were measured in en face images reconstructed from
three-dimensional SS-OCT images. Relationship between the PPA areas and patient
characteristics such as glaucoma, axial length, and age was statistically
evaluated using multivariate mixed-effects models. MAIN OUTCOME MEASURES: Areas
of the beta zone and the gamma zone PPA measured on en face OCT images. RESULTS:
Average +/- standard deviation area of the beta and the gamma zone was 0.64 +/-
0.79 and 0.16 +/- 0.30 mm2, respectively. In multivariate models, the gamma zone
significantly correlated with axial length (P = 0.001) but not with glaucoma (P =
0.944). In contrast, the beta zone significantly correlated with age (P = 0.0249)
and glaucoma (P = 0.014). CONCLUSIONS: En face images reconstructed from 3D SS
OCT data facilitated measurements of the beta and the gamma PPA zones even in
eyes with optic disc distortion. The OCT-defined beta zone is associated with
glaucoma and age, whereas the gamma zone correlated with myopia but not with
glaucoma. This study confirmed the clinical usefulness of OCT-based
classification of the PPA zones in distinguishing glaucomatous damage of the
optic nerve from myopic damage in non-highly myopic eyes.
PMID- 28414806
TI - Cost-effectiveness of nurse-led multifactorial care to prevent or postpone new
disabilities in community-living older people: Results of a cluster randomized
trial.
AB - OBJECTIVE: To evaluate the cost-effectiveness of nurse-led multifactorial care to
prevent or postpone new disabilities in community-living older people in
comparison with usual care. METHODS: We conducted cost-effectiveness and cost
utility analyses alongside a cluster randomized trial with one-year follow-up.
Participants were aged >= 70 years and at increased risk of functional decline.
Participants in the intervention group (n = 1209) received a comprehensive
geriatric assessment and individually tailored multifactorial interventions
coordinated by a community-care registered nurse with multiple follow-up visits.
The control group (n = 1074) received usual care. Costs were assessed from a
healthcare perspective. Outcome measures included disability (modified Katz
Activities of Daily Living (ADL) index score), and quality-adjusted life-years
(QALYs). Statistical uncertainty surrounding Incremental Cost-Effectiveness
Ratios (ICERs) was estimated using bootstrapped bivariate regression models while
adjusting for confounders. RESULTS: There were no statistically significant
differences in Katz-ADL index score and QALYs between the two groups. Total mean
costs were significantly higher in the intervention group (EUR 6518 (SE 472)
compared with usual care (EUR 5214 (SE 338); adjusted mean difference ?1457 (95%
CI: 572; 2537). Cost-effectiveness acceptability curves showed that the maximum
probability of the intervention being cost-effective was 0.14 at a willingness to
pay (WTP) of EUR 50,000 per one point improvement on the Katz-ADL index score and
0.04 at a WTP of EUR 50,000 per QALY gained. CONCLUSION: The current intervention
was not cost-effective compared to usual care to prevent or postpone new
disabilities over a one-year period. Based on these findings, implementation of
the evaluated multifactorial nurse-led care model is not to be recommended.
PMID- 28414807
TI - Interactions between the breast cancer-associated MUC1 mucins and C-type lectin
characterized by optical tweezers.
AB - Carbohydrate-protein interactions govern many crucial processes in biological
systems including cell recognition events. We have used the sensitive force probe
optical tweezers to quantify the interactions occurring between MGL lectins and
MUC1 carrying the cancer-associated glycan antigens mucins Tn and STn. Unbinding
forces of 7.6 pN and 7.1 pN were determined for the MUC1(Tn)-MGL and MUC1(STn)
MGL interactions, at a force loading rate of ~40 pN/s. The interaction strength
increased with increasing force loading rate, to 27 and 37 pN at a force loading
rate of ~ 310 pN/s. No interactions were detected between MGL and MUC1(ST), a
glycoform of MUC1 also expressed by breast carcinoma cells. Interestingly, this
glycan (ST) can be found on proteins expressed by normal cells, although in this
case not on MUC1. Additionally, GalNAc decorated polyethylene glycol displayed
similar rupture forces as observed for MUC1(Tn) and MUC1(STn) when forced to
unbind from MGL, indicating that GalNAc is an essential group in these
interactions. Since the STn glycan decoration is more frequently found on the
surface of carcinomas than the Tn glycan, the binding of MUC1 carrying STn to MGL
may be more physiologically relevant and may be in part responsible for some of
the characteristics of STn expressing tumours.
PMID- 28414808
TI - A longitudinal and experimental study of the impact of knowledge on the bases of
institutional trust.
AB - This study examined a knowledge-centered theory of institutional trust
development. In the context of trust in water regulatory institutions, the
moderating impact of knowledge was tested to determine if there were longitudinal
changes in the bases of institutional trust as a function of increases in
knowledge about a target institution. We hypothesized that as people learn about
an institution with which they were previously unfamiliar, they begin to form
more nuanced perceptions, distinguishing the new institution from other
institutions and relying less upon their generalized trust to estimate their
trust in that institution. Prior to having specific, differential information
about a new institution, we expected institutional trust to be a function of
generalized trust variables such as dispositional trust and trust in government.
The longitudinal experiment involved 185 college students randomly assigned to
one of three information conditions. Every 3 months for 15 months, participants
read information about water regulatory institutions or a control institution. At
each time point, participants reported their trust in and perceptions of the
trust- and distrust-worthiness of the water regulatory institutions. Participants
also completed measures of knowledge of water regulatory institutions,
dispositional trust, and governmental trust. Our manipulation check indicated
that, as expected, those in the experimental group increased in subjective
knowledge of water regulatory institutions to a greater extent than those in the
control condition. Consistent with our hypotheses, there was some evidence that,
compared to the control group, the experimental group relied less on their
general trust in government as a basis for their trust in water regulatory
institutions. However, contrary to our hypotheses, there was no evidence the
experimental group relied less on dispositional trust as a basis for
institutional trust. There also was some evidence the experimental group's trust
in water regulatory institutions was less affected by fluctuations of
trustworthiness (but not distrustworthiness) perceptions over time. This suggests
that knowledge results in the development of more stable institutional trust
attitudes, but that trustworthiness and distrustworthiness perceptions may
operate somewhat differently when impacting trust in specific institutions.
PMID- 28414810
TI - Changes in the effects of living with no siblings or living with grandparents on
overweight and obesity in children: Results from a national cohort study in
Japan.
AB - Effects of living without siblings and living with grandparents on overweight and
obesity may change with child's age. We aimed to examine these effects from early
childhood to school age at the national level in Japan. Subjects were 43,046
children born in Japan during two weeks in 2001 who were followed annually from
2.5 to 13 years of age in the Longitudinal Survey of Newborns in the 21st
Century. We used measured body height and weight reported by participants at each
survey and followed the criteria of the International Obesity Task Force to
define overweight and obesity. Random-effects logit models by sex, adjusted for
time-varying and time-invariant covariates, assessed odds ratios of overweight
and obesity for living without siblings and for living with grandparents at each
age. The likelihood of overweight and obesity was significantly higher at 8 years
and older among children living without siblings, compared with those living with
siblings, and odds ratios were highest at 11 years of age in boys (1.87, 95%
confidence interval [CI]: 1.49, 2.33) and at 10 and 13 years of age in girls
(1.75 [95% CI: 1.36, 2.23] and 1.73 [95% CI: 1.30, 2.31], respectively). It was
also significantly higher at 5.5 years and older among children living with
grandparents, compared with those living without grandparents, and odds ratios
were highest at 10 and 13 years of age in boys (1.53 [95% CI: 1.30, 1.80] and
1.54 [95% CI: 1.27, 1.86], respectively) and at 11 years of age in girls (1.51,
95% CI: 1.24, 1.84). In Japan, living without siblings and living with
grandparents may increase the likelihood of overweight and obesity at 8 and 5.5
years and older, respectively. Child's age should be considered during
formulation of strategies for prevention of overweight and obesity in these
groups.
PMID- 28414809
TI - Comparative expression profiling of testis-enriched genes regulated during the
development of spermatogonial cells.
AB - The testis has been identified as the organ in which a large number of tissue
enriched genes are present. However, a large portion of transcripts related to
each stage or cell type in the testis still remains unknown. In this study,
databases combined with confirmatory measurements were used to investigate testis
enriched genes, localization in the testis, developmental regulation, gene
expression profiles of testicular disease, and signaling pathways. Our
comparative analysis of GEO DataSets showed that 24 genes are predominantly
expressed in testis. Cellular locations of 15 testis-enriched proteins in human
testis have been identified and most of them were located in spermatocytes and
round spermatids. Real-time PCR revealed that expressions of these 15 genes are
significantly increased during testis development. Also, an analysis of GEO
DataSets indicated that expressions of these 15 genes were significantly
decreased in teratozoospermic patients and polyubiquitin knockout mice,
suggesting their involvement in normal testis development. Pathway analysis
revealed that most of those 15 genes are implicated in various sperm-related cell
processes and disease conditions. This approach provides effective strategies for
discovering novel testis-enriched genes and their expression patterns, paving the
way for future characterization of their functions regarding infertility and
providing new biomarkers for specific stages of spematogenesis.
PMID- 28414811
TI - Tissue expression profiles and transcriptional regulation of elongase of very
long chain fatty acid 6 in bovine mammary epithelial cells.
AB - In mammals, very long chain fatty acids (VLCFAs) perform pleiotropic roles in a
wide range of biological processes, such as cell membrane formation, cell signal
transduction, and endocrine regulation. Beef and milk are abundant of palmitic
acid which can be further elongated into stearic acid for synthesizing VLCFAs.
Elongase of very long chain fatty acid 6 (ELOVL6) is a rate-limiting enzyme for
converting palmitic acid to stearic acid. Consequently, investigating the tissue
expression patterns and transcriptional regulation of bovine ELOVL6 can provide
new insights into improving the composition of beneficial fats in cattle and
expanding the knowledge of transcriptional regulation mechanism among domestic
animals. In the current study, we found that bovine ELOVL6 expressed
ubiquitously. Dual-luciferase reporter assay identified that the core promoter
region (-130/-41 bp) was located in the second CpG island. In addition, the
deletion mutation of binding sites demonstrated that sterol regulatory element
binding transcription factor 1 (SREBF1) and specific protein 1 (SP1) both were
able to stimulate bovine ELOVL6 promoter activity independently, while resulting
the similar effect. To confirm these findings, further RNA interference assays
were executed in bovine mammary epithelial cells (BMECs). In summary, these data
suggest that bovine ELOVL6 expressed ubiquitously and is activated by SREBF1 and
SP1, via two binding sites present in the ELOVL6 promoter region between -130 bp
to -41bp.
PMID- 28414812
TI - Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and
vascular dysfunction in hyperhomocysteinemia.
AB - There is an emerging consensus that hyperhomocysteinemia is an independent risk
factor for cerebral vascular disease and that homocysteine-lowering therapy
protects from ischemic stroke. However, the mechanisms by which
hyperhomocysteinemia produces abnormalities of cerebral vascular structure and
function remain largely undefined. Our objective in this study was to define the
mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular
dysfunction and hypertrophy. Unlike previous studies, our experimental design
included a genetic approach to alter superoxide levels by using superoxide
dismutase 1 (SOD1)-deficient mice fed a high methionine/low folate diet to
produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet
caused elevated superoxide levels and impaired responses to endothelium-dependent
vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity
of these effects. The cross-sectional area of the pial arteriolar wall was
markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic
diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of
individual components of the vascular wall demonstrated a significant increase in
the content of smooth muscle and elastin. We conclude that superoxide is a key
driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this
model of dietary hyperhomocysteinemia. These findings provide insight into the
mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and
ischemic stroke.
PMID- 28414814
TI - An algorithm for separation of mixed sparse and Gaussian sources.
AB - Independent component analysis (ICA) is a ubiquitous method for decomposing
complex signal mixtures into a small set of statistically independent source
signals. However, in cases in which the signal mixture consists of both
nongaussian and Gaussian sources, the Gaussian sources will not be recoverable by
ICA and will pollute estimates of the nongaussian sources. Therefore, it is
desirable to have methods for mixed ICA/PCA which can separate mixtures of
Gaussian and nongaussian sources. For mixtures of purely Gaussian sources,
principal component analysis (PCA) can provide a basis for the Gaussian subspace.
We introduce a new method for mixed ICA/PCA which we call Mixed ICA/PCA via
Reproducibility Stability (MIPReSt). Our method uses a repeated estimations
technique to rank sources by reproducibility, combined with decomposition of
multiple subsamplings of the original data matrix. These multiple decompositions
allow us to assess component stability as the size of the data matrix changes,
which can be used to determinine the dimension of the nongaussian subspace in a
mixture. We demonstrate the utility of MIPReSt for signal mixtures consisting of
simulated sources and real-word (speech) sources, as well as mixture of unknown
composition.
PMID- 28414813
TI - DNA barcoding evaluation and implications for phylogenetic relationships in
Lauraceae from China.
AB - Lauraceae are an important component of tropical and subtropical forests and have
major ecological and economic significance. Owing to lack of clear-cut
morphological differences between genera and species, this family is an ideal
case for testing the efficacy of DNA barcoding in the identification and
discrimination of species and genera. In this study, we evaluated five widely
recommended plant DNA barcode loci matK, rbcL, trnH-psbA, ITS2 and the entire ITS
region for 409 individuals representing 133 species, 12 genera from China. We
tested the ability of DNA barcoding to distinguish species and as an alternative
tool for correcting species misidentification. We also used the rbcL+matK+trnH
psbA+ITS loci to investigate the phylogenetic relationships of the species
examined. Among the gene regions and their combinations, ITS was the most
efficient for identifying species (57.5%) and genera (70%). DNA barcoding also
had a positive role for correcting species misidentification (10.8%).
Furthermore, based on the results of the phylogenetic analyses, Chinese Lauraceae
species formed three supported monophyletic clades, with the Cryptocarya group
strongly supported (PP = 1.00, BS = 100%) and the clade including the Persea
group, Laureae and Cinnamomum also receiving strong support (PP = 1.00, BS =
98%), whereas the Caryodaphnopsis-Neocinnamomum received only moderate support
(PP = 1.00 and BS = 85%). This study indicates that molecular barcoding can
assist in screening difficult to identify families like Lauraceae, detecting
errors of species identification, as well as helping to reconstruct phylogenetic
relationships. DNA barcoding can thus help with large-scale biodiversity
inventories and rare species conservation by improving accuracy, as well as
reducing time and costs associated with species identification.
PMID- 28414815
TI - Isolation of human explant derived cardiac stem cells from cryopreserved heart
tissue.
AB - The value of preserving high quality bio specimens for fundamental research is
significant as linking cellular and molecular changes to clinical and
epidemiological data has fueled many recent advances in medicine. Unfortunately,
storage of traditional biospecimens is limited to fixed samples or isolated
genetic material. Here, we report the effect of cryopreservation of routine
myocardial biopsies on explant derived cardiac stem cell (EDC) culture outcomes.
We demonstrate that immediate cryopreservation or delayed cryopreservation after
suspension within cardioplegia for 12 hours did not alter EDC yields,
proliferative capacity, antigenic phenotype or paracrine signature.
Cryopreservation had negligible effects on the ability of EDCs to adopt a cardiac
lineage, stimulate new vessel growth, attract circulating angiogenic cells and
repair injured myocardium. Finally, cryopreservation did not influence the
ability of EDCs to undergo genetic reprogramming into inducible pluripotent stem
cells. This study establishes a means of storing cardiac samples as a retrievable
live cell source for cardiac repair or disease modeling.
PMID- 28414816
TI - Fourier transform power spectrum is a potential measure of tissue alignment in
standard MRI: A multiple sclerosis study.
AB - Loss of tissue coherency in brain white matter is found in many neurological
diseases such as multiple sclerosis (MS). While several approaches have been
proposed to evaluate white matter coherency including fractional anisotropy and
fiber tracking in diffusion-weighted imaging, few are available for standard
magnetic resonance imaging (MRI). Here we present an image post-processing method
for this purpose based on Fourier transform (FT) power spectrum. T2-weighted
images were collected from 19 patients (10 relapsing-remitting and 9 secondary
progressive MS) and 19 age- and gender-matched controls. Image processing steps
included: computation, normalization, and thresholding of FT power spectrum;
determination of tissue alignment profile and dominant alignment direction; and
calculation of alignment complexity using a new measure named angular entropy. To
test the validity of this method, we used a highly organized brain white matter
structure, corpus callosum. Six regions of interest were examined from the left,
central and right aspects of both genu and splenium. We found that the dominant
orientation of each ROI derived from our method was significantly correlated with
the predicted directions based on anatomy. There was greater angular entropy in
patients than controls, and a trend to be greater in secondary progressive MS
patients. These findings suggest that it is possible to detect tissue alignment
and anisotropy using traditional MRI, which are routinely acquired in clinical
practice. Analysis of FT power spectrum may become a new approach for advancing
the evaluation and management of patients with MS and similar disorders. Further
confirmation is warranted.
PMID- 28414817
TI - Correction: Assessment of Universal Healthcare Coverage in a District of North
India: A Rapid Cross-Sectional Survey Using Tablet Computers.
AB - [This corrects the article DOI: 10.1371/journal.pone.0157831.].
PMID- 28414818
TI - TGFbeta/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in
colon cancer cells.
AB - In this study, we have uncovered a novel crosstalk between TGFbeta and IGF-1R
signaling pathways. We show for the first time that expression and activation of
IRS-1, an IGF-1R adaptor protein, is decreased by TGFbeta/Smad3 signaling. Loss
or attenuation of TGFbeta activation leads to elevated expression and
phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell
proliferation, decreased apoptosis and increased tumor growth in vitro and in
vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated
oncogenic phenotypes, indicating that TGFbeta/Smad3 signaling inhibits cell
proliferation and increases apoptosis at least partially through the inhibition
of IRS-1 expression and activation. Additionally, the TGFbeta/Smad3/IRS-1
signaling axis regulates expression of cyclin D1 and XIAP, which may contribute
to TGFbeta/Smad3/IRS-1-mediated cell cycle progression and survival. Given that
loss of TGFbeta signaling occurs frequently in colon cancer, an important
implication of our study is that IRS-1 could be a potential therapeutic target
for colon cancer treatment.
PMID- 28414819
TI - Glycemic markers and relation with arterial stiffness in Caucasian subjects of
the MARK study.
AB - BACKGROUND: Effect of prediabetes and normal glucose on arterial stiffness
remains controversial. The primary aim of this study was to investigate the
relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and
glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV)
and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was
to analyse this relationship by glycaemic status. METHODS: Cross-sectional study.
Setting: Primary care. Participants: 2,233 subjects, 35-74 years. Measures: FPG
(mg/dL) and HbA1c (%) of all subjects were measured using standard automated
enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals
(breakfast, lunch and dinner) for one day using an Accu-chek (r) glucometer. CAVI
was measured using a VaSera VS-1500(r) device (Fukuda Denshi), and baPWV was
calculated using a validated equation. RESULTS: CAVI and baPWV values were
significantly higher in subjects with diabetes mellitus than in glucose normal
and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated
with CAVI and baPWV. The beta regression coefficient for: HbA1c was 0.112 (CI 95%
0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was
0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with
baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to
0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status,
FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with
type 2 diabetes mellitus. CONCLUSION: FPG, PG and HbA1c show a positive
association with CAVI and baPWV, in Caucasian adults with intermediate
cardiovascular risk factors. When analysing by hyperglycaemic status, the
association is only maintained in subjects with type 2 diabetes mellitus. TRIAL
REGISTRATION: Clinical Trials.gov Identifier: NCT01428934. Registered 2 September
2011. Retrospectively registered. Last updated September 8, 2016.
PMID- 28414820
TI - Transcriptome analysis of the epidermis of the purple quail-like (q-lp) mutant of
silkworm, Bombyx mori.
AB - A new purple quail-like (q-lp) mutant found from the plain silkworm strain 932VR
has pigment dots on the epidermis similar to the pigment mutant quail (q). In
addition, q-lp mutant larvae are inactive, consume little and grow slowly, with a
high death rate and other developmental abnormalities. Pigmentation of the
silkworm epidermis consists of melanin, ommochrome and pteridine. Silkworm
development is regulated by ecdysone and juvenile hormone. In this study, we
performed RNA-Seq on the epidermis of the q-lp mutant in the 4th instar during
molting, with 932VR serving as the control. The results showed 515 differentially
expressed genes, of which 234 were upregulated and 281 downregulated in q-lp.
BLASTGO analysis indicated that the downregulated genes mainly encode protein
binding proteins, membrane components, oxidation/reduction enzymes, and
proteolytic enzymes, whereas the upregulated genes largely encode cuticle
structural constituents, membrane components, transport related proteins, and
protein-binding proteins. Quantitative reverse transcription PCR was used to
verify the accuracy of the RNA-Seq data, focusing on key genes for biosynthesis
of the three pigments and chitin as well as genes encoding cuticular proteins and
several related nuclear receptors, which are thought to play key roles in the q
lp mutant. We drew three conclusions based on the results: 1) melanin, ommochrome
and pteridine pigments are all increased in the q-lp mutant; 2) more cuticle
proteins are expressed in q-lp than in 932VR, and the number of upregulated
cuticular genes is significantly greater than downregulated genes; 3) the
downstream pathway regulated by ecdysone is blocked in the q-lp mutant. Our
research findings lay the foundation for further research on the developmental
changes responsible for the q-lp mutant.
PMID- 28414821
TI - Constructing a biodiversity terminological inventory.
AB - The increasing growth of literature in biodiversity presents challenges to users
who need to discover pertinent information in an efficient and timely manner. In
response, text mining techniques offer solutions by facilitating the automated
discovery of knowledge from large textual data. An important step in text mining
is the recognition of concepts via their linguistic realisation, i.e., terms.
However, a given concept may be referred to in text using various synonyms or
term variants, making search systems likely to overlook documents mentioning less
known variants, which are albeit relevant to a query term. Domain-specific
terminological resources, which include term variants, synonyms and related
terms, are thus important in supporting semantic search over large textual
archives. This article describes the use of text mining methods for the automatic
construction of a large-scale biodiversity term inventory. The inventory consists
of names of species, amongst which naming variations are prevalent. We apply a
number of distributional semantic techniques on all of the titles in the
Biodiversity Heritage Library, to compute semantic similarity between species
names and support the automated construction of the resource. With the
construction of our biodiversity term inventory, we demonstrate that
distributional semantic models are able to identify semantically similar names
that are not yet recorded in existing taxonomies. Such methods can thus be used
to update existing taxonomies semi-automatically by deriving semantically related
taxonomic names from a text corpus and allowing expert curators to validate them.
We also evaluate our inventory as a means to improve search by facilitating
automatic query expansion. Specifically, we developed a visual search interface
that suggests semantically related species names, which are available in our
inventory but not always in other repositories, to incorporate into the search
query. An assessment of the interface by domain experts reveals that our query
expansion based on related names is useful for increasing the number of relevant
documents retrieved. Its exploitation can benefit both users and developers of
search engines and text mining applications.
PMID- 28414822
TI - 2-dimensional shear wave elastography: Interobserver agreement and factors
related to interobserver discrepancy.
AB - PURPOSE: To evaluate the interobserver reproducibility of two-dimensional shear
wave elastography (2D-SWE) in measuring liver stiffness (LS) and to investigate
factors related to liver 2D-SWE. MATERIALS AND METHODS: A prospective study was
conducted between August 2011 and August 2012 in rheumatoid arthritis patients
who had been treated with methotrexate. Interobserver reproducibility of 2D-SWE
was evaluated, and the relationship between interobserver difference in LS and
related factors was analyzed using linear regression analyses. We considered age,
sex, alanine transaminase, cholesterol, body mass index (BMI), and waist
circumference as clinical factors, and the mean value of standard deviation
(SDM), its difference between two examiners, mean diameter of the regions of
interest (ROIM), and its difference in the elasticity map as investigation
factors. The cut-off value for significant factors to predict interobserver
discrepancies in LS-based fibrosis stage was also inspected. RESULTS: In total,
176 patients were enrolled. The intraclass correlation coefficient between the
two examiners was 0.784. In the univariate analysis, SDM and ROIM were
independently associated with interobserver differences in LS as well as BMI,
waist circumference, and the difference of ROI, but SDM and ROIM were the only
ones significantly related in multivariate analysis (p<0.001 and p = 0.021,
respectively). The best cut-off value for SDM in predicting interobserver
discrepancy in LS-based fibrosis stage was 1.4. CONCLUSIONS: Interobserver
reproducibility of 2D-SWE for measuring LS was good and SDM was the most
significantly associated factor with interobserver differences in LS and
interobserver discordance in LS-based fibrosis stage.
PMID- 28414824
TI - [Sociology and health: new developments and pending challenges].
PMID- 28414823
TI - Comparing in vitro and in vivo virulence phenotypes of Burkholderia pseudomallei
type G strains.
AB - Burkholderia pseudomallei (Bpm) is a saprophytic rod-shaped gram-negative
bacterium and the causative agent of melioidosis. This disease has previously
been described as endemic in areas such as northern Australia and Southeast Asia,
but, more recently, a better understanding of the epidemiology of melioidosis
indicated that the disease is distributed worldwide, including regions of the
Americas and Africa. A 16S-23S rDNA internal transcribed spacer (ITS) typing
system has been developed for Bpm and has revealed that ITS types C, E, and
hybrid CE are mainly associated with Australia and Southeast Asia while type G
strains are more associated with cases of melioidosis in the Western Hemisphere.
The purpose of the current study was to determine the in vitro and in vivo
virulence profiles of the understudied Bpm type G strains Ca2009, Ca2013a,
Mx2013, and 724644 and compared such phenotypes to the commonly studied Bpm type
C strain K96243. We evaluated virulence by measuring invasion/uptake and survival
of these Bpm strains in murine respiratory epithelial LA-4 cells and alveolar
macrophage MH-S cells using different multiplicity of infections (MOIs of 1 and
10). We also calculated the lethal dose 50 values (LD50) in BALB/c mice that were
inoculated intranasally with either Ca2009, Ca2013a, or Mx2013. Overall, the
virulence and lethality phenotypes of Bpm type G strains were similar to the Bpm
type C strain K96243. Additional comparative analyses between the Bpm ITS types
may lead to a better understanding of the contribution of the ITS type to the
epidemiology and ecology of Bpm strains.
PMID- 28414826
TI - [Tensions between the (il)legal and the (il)legitimate in professional health
practices regarding women who seek abortion].
AB - The implementation of a pre- and post-abortion health care strategy, adopted in
2004 in Uruguay within a restrictive legal context prior to the decriminalization
of abortion in 2012, opened a window of opportunity to link women facing unwanted
pregnancies and abortion to health services in order to prevent unsafe abortion
practices. This article looks into the tensions generated by the change of focus
from maternal-child health to health and sexual and reproductive rights, and how
those tensions operate. Using semi-structured interviews and focus groups, the
practices and perception and assessment frameworks of professionals in their care
of women facing unwanted pregnancy and abortion in the National Integrated Health
System in Montevideo are analyzed. The results offer insights into some of the
barriers and difficulties that can currently be observed in the implementation of
the new law.
PMID- 28414825
TI - [Medical power and the crisis in bonds of trust within contemporary medicine].
AB - Based on the Brazilian context, this paper addresses medical power in terms of
the current conflicts in the intersubjective relationships that doctors establish
in their work, conflicts considered here as a product of a crisis of trust
connected to recent historical transformations in the medical practice. Reading
these conflicts as questions of an ethical and moral order, we use Hanna Arendt's
theoretical formulations to further analyze this crisis of trust. In this way,
utilizing the concepts of "crisis," "tradition," "power," "authority," and
"natality," we search for new meanings regarding these conflicts, enabling new
paths and solutions that avoid nostalgia for the past.
PMID- 28414827
TI - [The temporal dimension of drugs: a sociological analysis based on a category key
to the study of health-disease-care processes].
AB - The temporal dimensions that shape the senses and practices of men and women who
are poly-consumers of psychoactive substances, 18-35 years of age, and living in
the metropolitan area of Buenos Aires were analyzed. Using a qualitative
approach, 29 individual in-depth interviews were carried out and then analyzed
through a constant comparative analysis process between the categories generated
from the data obtained and the theoretical concepts. From the analysis, practices
and meanings emerge that regulate the diverse temporalities that underlie drug
consumption: feelings related to body rhythms, periods between consumptions, the
timing of phases of the life cycle, or unspecific temporalities that become an
adequate "moment" for consumption. These practices require that particular
attention be paid to time, as this enables the flexibility to consume without
being a consumer, to use drugs without being addicted to them.
PMID- 28414828
TI - [The agribusiness industry in northwestern Mexico and the health of female
farmworkers: a proposal for study].
AB - This article seeks to outline the structure of the export-oriented agribusiness
industry in northwestern Mexico, so as to analyze the conditions of vulnerability
of female farmworkers in terms of their access to health services and the medical
attention they receive. Using a qualitative approach, focus groups and interviews
were carried out with farmworkers and subject experts pertaining to academia and
civil society. Their narratives were then analyzed using Pierre Bourdieu's
concept of field. The primary results demonstrate a lack of access to health
services and social security, and describe the main actors and their positions
with respect to the vulnerability of this population.
PMID- 28414829
TI - [From sociology in medicine to the sociology of collective health: contributions
toward a necessary reflexivity].
AB - This text looks at the difference between sociology in medicine (collaborator of
health institutions) and the sociology of medicine (independent of health
institutions). If consistent, sociology in medicine should become a sociology of
medicine. As an example, it is shown how the study of the social determinants of
health and illness begins by assuming non-problematically the ontological reality
of health and illness, but ends up problematizing the very concept of health
disease, demonstrating that the study of health determinants also requires the
study of the determinants of the social construction of disease. The urgent
necessity of objectifying collective health itself is argued. By applying
sociological tools we can examine the so-called objective factors in the
determination of health and disease, the socially constructed nature of these
categories of knowledge, and the struggles and power relations that determine
whether or not such categories are viable.
PMID- 28414830
TI - [Prevalence and evolution of helmet use in motorcycle riders in an Argentine city
(Mar del Plata, 2006-2014)].
AB - Traffic collisions involving motorcyclists are a growing problem in low and
middle income countries. Helmet use is the foremost protective measure for this
group of road users, however many riders do not wear them. The objective of the
present study is to report the changes in helmet use during the period 2006-2014
in an Argentine city and discover associated factors for the year 2014. The
sample includes more than 6,900 observations of motorcyclists carried out during
the years 2006 (n=962), 2008 (n=977), 2012 (n=2,542), and 2014 (n=2,466). The
data indicates a progressive increase in helmet use over time, but differences
due to gender and type of rider remain. Factors associated to helmet use in
motorcycle drivers during 2014 were: passenger helmet use, motorcycle type,
license plate use and gender. Although the results are positive, it is necessary
to be attentive to the negative consequences of the growing fleet of motorcycles.
PMID- 28414831
TI - [Child nutritional status in contexts of urban poverty: a reliable indicator of
family health?]
AB - This work questions the premise that the nutritional status of children under six
years of age is a reliable indicator of family health. To do so, a research
strategy based in case studies was carried out, following a qualitative design
(participant observation and semistructured interviews using intentional
sampling) and framed within the interpretivist paradigm. The anthropometric
measurements of 20 children under six years of age attending the local Child Care
Center in Villa La Tela, Cordoba were evaluated. Nutritional status was
understood as an object that includes socially determined biological processes,
and was therefore posited analytically as a cross between statistical data and
its social determination. As a statistic, child nutritional status is merely
descriptive; to assist in the understanding of its social determination, it must
be placed in dialectical relationship with the spheres of sociability proposed to
analyze the reproduction of health problems.
PMID- 28414832
TI - [Integrality in the health care perspective: an experience of the Unified Health
System in Brazil].
AB - Starting with a discussion of the biomedical model and its implications in the
shaping of healthcare professionals and health practices, this article analyzes
the concept of integrality as associated with the Unified Health System (SUS)
[Sistema Unico de Salud] in Brazil. Particular attention is paid to the disputes
regarding the meaning of integrality and the ways of putting the concept into
practice in everyday health care work. Based in a research study conducted at the
national level, the authors suggest two aspects crucial to fostering integrality:
an ethical-political project founded in the recognition that other people's lives
are worthwhile and enriching; as well as the existence of additional spaces
conducive to discovering diverse ways of producing life, in which integrality in
health care is also possible and powerful. The authors affirm the relevance of
this process as a contribution to the continual construction of the SUS in
Brazil.
PMID- 28414833
TI - [Concentration and inequalities in the financing of obras sociales after
deregulation: a comparative analysis of the years 2004 and 2011].
AB - In Argentina, during the decade of the 1990s major changes were introduced into
the regulatory framework of the national obras sociales, or union-based health
coverage plans. Using data from the Federal Administration of Public Income
(AFIP) [Administracion Federal de Ingresos Publicos], this study evaluates for
the years 2004 and 2011: a) the importance of obras sociales within the
healthcare system, b) the degree of concentration of this health social security
subsystem, and c) the inequalities in the availability of funds among the obras
sociales and their beneficiaries. The results show an increased importance of
obras sociales within the Argentine health system. The concentration of funds
distributed to the most important institutions within the subsystem showed no
change, while the concentration of contributors to these institutions slightly
increased and that of beneficiaries decreased. Finally, a reduction of the
inequalities in funds per beneficiary received by different institutions was
observed. This trend can be explained, among other factors, by the attenuation of
wage differentials between branches of economic activity and the actions of the
so-called Solidarity Redistribution Fund.
PMID- 28414834
TI - [Salud Colectiva: taking a stand in favor of open access].
PMID- 28414835
TI - [Thinking about health once again: programs and territories].
AB - This article, of a conceptual nature, uses critical theory to discuss the
programmatic logic within the sociosanitary field as a technical answer without
any questions, provided to territories or spaces with questions awaiting
translation. The purpose is to put programmatic logic, which is the legacy of
public health planning and an expression of instrumental reason, into discussion,
and in this way examine the temporal-spatial conception as an axis for thinking
and acting within the complexity of the social world, recognizing other knowledge
and practices. The questions, answers, knowledge and actions in the sociosanitary
field constitute the focus of a reflection rooted in concepts that seek to
deconstruct the ideological project represented by health programs through an
analysis of their scientific basis (the epistemological component of the
technical), which is antagonistic to any emancipatory project.
PMID- 28414836
TI - [An ethnographic approach to the concepts of health and disease in the Turkana
tribe: a project to improve the health of the nomads of the Ilemi Triangle,
Kenya].
AB - This paper aims to provide a broad view of the Turkana tribe of the Ilemi
Triangle in northwestern Kenya, especially regarding the way the members of this
nomadic ethnic group understand and shape their own construct of health and
disease. It is based in an ethnographic study carried out in July and August
2014, including participant observation of 15 villages of the Turkana tribe,
formal interviews and in-depth interviews carried out with the collaboration of
two translators of the tribe and a nurse. Field notes as well videos and audio
records were captured and transcribed for later analysis. Among the primary
results of this study, it should be highlighted that the concepts of both health
and disease differ greatly from the western approach that external projects bring
with them a priori and it is likely that the lack of adherence to these projects
is related to the scant cultural knowledge regarding such constructs on the part
of the health professionals.
PMID- 28414837
TI - [The representation of health care services in Mexican television: potential
consequences for health subjectivities].
AB - The objective of this paper is to analyze the representation of health services
in Mexican television, considering that television plays an important role in the
production and reproduction of the social meanings of health. A descriptive study
analyzed the contents of 672 hours of continuous television (media flows)
broadcast in Mexico in 2011, examining advertising, television shows and
newscasts. The analysis of all these messages shows that the representation of
private care services predominates. When public care services are mentioned, the
communication is mainly regarding the Seguro Popular de Salud [Popular Health
Insurance, for those with low incomes], while the social security model of care
is underrepresented. We therefore conclude that television favors the two first
models of health care. This kind of representation could hold potential
consequences for health subjectivities.
PMID- 28414838
TI - [Health and working conditions of high school and university teachers in Mendoza:
between commitment and emotional distress].
AB - With the objective of analyzing aspects related to the perception of working
conditions and their impact on health in the teachers and professors who work for
the Universidad Nacional de Cuyo (UNCuyo) in Mendoza, Argentina, this work
analyzes the results of the Primer Censo de Condiciones y Salud Laboral [First
Census on Health and Working Conditions]. The census was conducted in late 2013
in two academic units (one at the high school level and the other at the
university level), including 193 educators. The exploration set out to
characterize the teaching staff and the conditions affecting their health,
primarily with respect to psycho-social health. In order to do, so a self
administered questionnaire was applied, the dimensions of which were discussed in
sensitivity workshops with educators who helped to formulate the data collection
instrument. Among the primary results emerge the physical and emotional burnout
of these highly skilled workers, owing to the combined effect of their committed
response to the demands of their work and the deterioration (both material and
symbolic) of the conditions in which they carry out that work.
PMID- 28414839
TI - [The configuration of nursing labor conditions in the Buenos Aires Metropolitan
Area: An analysis at the intersection of the gender order and the organization of
the health system].
AB - The article explores two key factors which contribute to shape the poor working
conditions of nursing in Argentina. A first objective focuses on exploring the
effect of the occupation's care component, closely associated with cultural
images of "inherent" female qualities, on working conditions. A second objective
aims to examine the way in which the organization of health services provision in
Argentina intensifies the vulnerability of this occupation. Regarding the
methodology, the fieldwork conducted in the Metropolitan Area of Buenos Aires
included in-depth interviews with key informants and group interviews with
nurses. Among the results, on the one hand it is shown how the social devaluation
of care is reflected in the discourse of those who perform the occupation as well
as in institutional practices and policies in the health sector. On the other
hand, it is shown that the decentralization and fragmentation of the health
system act as additional obstacles hampering the articulation of labor demands.
PMID- 28414840
TI - [Quali-quantitative study of nutritional status and eating patterns in children
aged 1-3 years from low-income families in two population groups with different
productive activities (Buenos Aires, Argentina), 2007-2008].
AB - The aim of this article is to describe the nutritional status and eating patterns
of children aged 1-3 years from low-income families who reside in areas with
different productive activities: primary production and production of goods and
services. A descriptive cross-sectional study was performed with a qualitative
and quantitative methodology, evaluating anthropometric and biochemical
nutritional status, food intake, economic and demographic characteristics,
dietary practices and representations. The results show that children from areas
of primary production had a lower prevalence of anemia and iron deficiency. They
also had a higher consumption of energy, calcium, zinc, vitamin A and protein and
a greater diversity and quality in food consumption. We can conclude that the
geographical context of families closer to sources of primary production favors
interaction with individuals outside of the family, expanding both the informal
social network and access to better quality nutritional food.
PMID- 28414841
TI - [Analysis of the trend and impact of mortality due to external causes: Mexico,
2000-2013].
AB - The objective of this study was to analyze mortality due to the main external
causes of death (traffic accidents, other accidents, homicides and suicides) in
Mexico, calculating the years of life lost between 0 and 100 years of age and
their contribution to the change in life expectancy between 2000 and 2013, at the
national level, by sex and age group. Data came from mortality vital statistics
of the Instituto Nacional de Estadistica y Geografia (INEGI) [National Institute
of Statistics and Geography]. The biggest impact in mortality due to external
causes occurred in adolescent and adult males 15-49 years of age; mortality due
to these causes remained constant in males and slightly decreased in females.
Mortality due to traffic accidents and other accidents decreased, with a positive
contribution to life expectancy, but this effect was canceled out by the increase
in mortality due to homicides and suicides. Mortality due to external causes can
be avoided through interventions, programs and prevention strategies as well as
timely treatment. It is necessary to develop multidisciplinary studies on the
dynamics of the factors associated with mortality due to these causes.
PMID- 28414842
TI - [The challenge of inclusion in mental health: an analysis of a community center
and its work with social bonds].
AB - Social inclusion is a key component of transformations in mental health care,
because it takes into account the benefits of community life for both those with
mental illness and the other members of the community. In order to understand the
scope of inclusion within mental health, 45 participants of a community center
linked to a psychiatric hospital discharge program which explicitly seeks to
provide social inclusion were interviewed. The possible changes in social
relationships between users and other community members based in their sustained
daily interactions in the community center were explored. Results suggest that
the building of social bonds, as part of informal support networks, is one of the
benefits of attending the community center. Positive changes in ideas regarding
people with "mental illness" were also observed, although these ideas seemed to
be more connected to the notion of integration than to social inclusion.
PMID- 28414844
TI - [Contextualized editorial practices: Carlos Augusto Monteiro and the journal
Revista de Saude Publica].
AB - This text is part of a series of interviews that seek to explore diverse editing
and publication experiences and the similar difficulties Latin America journals
face, in order to begin to encounter contextualized solutions that articulate
previously isolated efforts. In this interview, carried out in July 2015 in the
Instituto de Salud Colectiva [Institute of Collective Health] of the Universidad
Nacional de Lanus, Carlos Augusto Monteiro speaks to us about funding, work
processes, technological innovations, and establishing teams and roles. He
analyzes the importance of Latin American journals as a platform for spreading
research relevant to national agendas, and the connection between journal
performance, the quality of graduate training programs and research quality.
PMID- 28414843
TI - [Violence in social networks: an exploration of the online expressions of teens
from marginalized areas of Greater Buenos Aires].
AB - This paper explores the online expressions of violence perpetrated or experienced
by adolescents from marginalized areas of Greater Buenos Aires, Argentina. Using
a qualitative methodology, four specific events were examined: threats, "bondis"
[fights], cyberbullying and displays of mourning. To do so, 20 in-depth
interviews and 3,000 virtual observations of profiles in the social network
Facebook were carried out. Among the main results, it was seen that most
expressions of violence are part of an offline-online dynamic. Empirical evidence
is also offered based upon which it can be affirmed that the expressions of
violence of these teenagers are developed around the culture of "aguante" [fierce
loyalty]. The article ponders the extent to which, in the iconic platform of the
option "like," these expressions are implicitly functional to the social network
or, to the contrary, or whether they allow displacements and significant
reappropriations on the part of users. New questions arise about the use of these
tools by adolescents from marginalized areas and the need for more complex
approaches to examine these phenomena.
PMID- 28414845
TI - [Contributions towards an "essential" medicine strategy for Latin America].
PMID- 28414846
TI - Clinical trials in Latin America: implications for the sustainability and safety
of pharmaceutical markets and the wellbeing of research subjects.
AB - This study sought to verify whether drugs approved by the US Food and Drug
Administration (FDA) were registered, commercialized and sold at affordable
prices in the Latin American countries where they had been tested, as well as to
ascertain their contribution to the quality of the pharmaceutical market. The
list of New Molecular Entities (NMEs) approved by the FDA in 2011 and 2012 was
consulted to determine the countries where pivotal trials were conducted.
Affordability was assessed as a proportion of income and information on safety
and efficacy was gathered from independent drug bulletins. In the study years, 33
medications were tested in 12 Latin American countries. Only 60% of the expected
registrations had been completed by September 2014. With one exception, all
products for which pricing information was obtained (n=18) cost more than one
monthly minimum wage in all countries. Only five drugs were classified as "could
be better than available treatments." Just one of the NMEs responds to the health
care priorities in low and middle income countries.
PMID- 28414847
TI - [Collective health in Brazil: analyzing the institutionalization process].
AB - This work first analyzes the construction of a typology of the studies on
collective health and its institutionalization process in Brazil, in which three
stages are proposed: the preventive project, social medicine and collective
health. Secondly, the work examines the phases of institutionalization,
disciplinarization and professionalization of collective health in Brazil. Within
the institutionalization phase, the study analyzes connectivity and
communication, regularization of discourses and practices, the construction of a
separate identity and political actions, and the incorporation and legitimation
of these elements. It is concluded that the trajectory of the construction of
collective health is marked by three dimensions: the theoretical-critical, the
political-sanitary and the pedagogical-professional.
PMID- 28414848
TI - [Abstract bodies, concrete risks: clinical devices and the health of ova donors
in Argentine reproductive medicine].
AB - Using a methodological perspective grounded in science and technology studies,
this article analyzes two sociotechnical devices used in Argentine reproductive
medicine (biostatistical measures and donation registries) with the aim of
controlling both the so-called "genetic risk" arising from the use of donated ova
as well as the health risks to female donors. By examining how the deployment of
monitoring criteria disregards the specificity of ova donation, the article
suggests that it is not the absence of control measures and clinical criteria
that produces an inadequate monitoring of such risks, but rather the concrete
ways in which such measures are implemented that results in potential harms to
the health of female donors.
PMID- 28414849
TI - [The rights of the dying: the refusal of medical treatments in Argentine courts].
AB - This paper addresses the judicialization of end of life medical decision-making,
as part of the advance of the justice system in the regulation of medical
practice and the rise of recognition of patient autonomy. The article analyzes,
from a sociological standpoint, legal decisions regarding treatment refusal at
the end of life produced by the Argentine courts between 1975 and 2015. Based on
a qualitative design, 38 sentences collected from jurisprudential databases using
key terms were analyzed. First, judicialized cases during the period are
described; these are characterized by a high proportion of claims presented by
health institutions, a pro-treatment bias in the legal actions requested, and a
high percentage of unnecessary litigation in the absence of conflicts or in
situations that do not require court intervention. Second, legal and extralegal
factors affecting the justiciability of decisions to refuse or withdraw medical
treatments, such as changes in the law and processes of politicization of claims,
are analyzed.
PMID- 28414850
TI - [Water resource quality as related to economic activity and health patterns in
Sonora, Mexico].
AB - The aim of this work is to analyze the spatial distribution of potential
pollution pathways of water resources given the economic activity in the Mexican
border state of Sonora and propose a regional distribution in relation to cancer
mortality rates across the state. The methodology is based in an exploratory and
inferential data analysis using two sources of primary data: wastewater discharge
concessions registered in the Public Registry on Water Rights [Registro Publico
de Derechos de Agua] (REPDA) and the records generated by the National Health
Information System [Sistema Nacional de Informacion en Salud] (SINAIS) in the
period 1998-2011 based on the International Classification of Disease (ICD-10).
The spatial concentration analysis allows for the identification of specific
cancer mortality causes at the regional level. Results indicate that the
projected adjustments to the regulation NOM-250-SSA1-2014, which controls a
subset of pollutants common in mining activity surroundings, is a matter of
regional concern.
PMID- 28414851
TI - [Bilingual guides: a strategy to decrease cultural barriers to health care access
in the Wayuu communities of Maicao, Colombia].
AB - The article examines the use of bilingual guides to decrease cultural barriers to
health care access in the Wayuu indigenous communities of Colombia. Within a
larger project on HIV carried out between 2012 and 2014, 24 interviews were
conducted with key actors in the administrative and health areas, including Wayuu
bilingual guides. As a result of the qualitative analysis, the study identified
three cultural barriers to health care access: a) language; b) the Wayuu
worldview regarding the body, health, and illness; and c) information about
sexual and reproductive health and HIV not adapted to the Wayuu culture. The
study identifies the bilingual guides as key actors in reducing these barriers
and concludes with a discussion of the role of the guides, the tensions inherent
to their work, and the complexity of their contributions as cultural mediators.
PMID- 28414853
TI - [Excessive osteoporosis screening in women under 65 years: a cross-sectional
study].
AB - Overuse of osteoporosis screening in women at low risk of fracture may lead to
overdiagnosis, inappropriate treatment and medicalization. The objective of this
work was to estimate the proportion of women aged 45 to 64 enrolled in a private
health insurance plan in Buenos Aires undergoing hip dual-energy x-ray
absorptiometry (DXA) in 2011 without meeting osteoporosis screening criteria. In
this cross-sectional study, 4310 women of this age range that had undergone a hip
DXA were identified. A randomly selected sub-group of 401 women was then assessed
for the presence of risk factors for osteoporosis and complete data were
retrieved for 178 women. Appropriate screening was defined by two criteria: 1)
having a 10-year fracture risk higher than that of a 65-year old woman (estimated
using the FRAX(r) tool); 2) having at least one risk factor for fracture. It was
found that 86.5% of the women who underwent hip DXA did not exceed the minimum 10
year fracture risk threshold required for screening; 5.8% of them had
osteoporosis and 61.0% osteopenia. According to the second criterion, 49.4% had
no risk factors, 3.4% of these women had osteoporosis and 62.5% osteopenia. The
results show that at least half the women screened did not meet osteoporosis
screening criteria.
PMID- 28414852
TI - [Access to oral health services in children under twelve years of age in Peru,
2014].
AB - The aim of the study was to explore the patterns of dental health services access
in children under twelve years of age in Peru. Data from 25,285 children under 12
years who participated in the Demographic and Family Health Survey of 2014 were
reviewed. An exploratory spatial analysis was performed to project the
proportions of children with access to dental health services, according to
national regions, type of health service and urban or rural place of residence.
The results show that of the total sample, 26.7% had access to dental health
services in the last six months, 39.6% belonged to the age group 0-4 years, 40.6%
lived in the Andean region and 58.3% lived in urban areas. The regions of
Huancavelica, Apurimac, Ayacucho, Lima and Pasco had the highest percentages of
access nationwide. In conclusion, there is low access to dental health services
in the population under 12 years of age in Peru. The spatial distribution of
access to dental health services allows regions to be identified and grouped
according to similar access patterns, in order to better focus public health
actions.
PMID- 28414854
TI - [Contextualized editorial practices: Maria Cecilia de Souza Minayo and the
journal Ciencia & Saude Coletiva].
AB - This interview forms part of a series of dialogues that Salud Colectiva has been
holding with key editors in the field, with the purpose of examining the similar
difficulties confronted by Latin American journals and the diverse ways the
journals have faced these difficulties as a likely starting point for uncovering
contextualized solutions. In this interview, carried out in 2015 in the Instituto
de Salud Colectiva of the Universidad Nacional de Lanus, Maria Cecilia de Souza
Minayo speaks to us about the context in which the journal Ciencia & Saude
Coletiva emerged, the political disputes existing within the collective health
field, and the relevance of debate as a constitutive process of science itself.
Additionally, Minayo analyzes both the importance of funding to the growth of a
journal and the problems and difficulties in obtaining funds, which puts into
evidence the lack of policy regarding scientific publishing in Brazil.
PMID- 28414855
TI - Green listed-a CRISPR screen tool.
AB - Motivation: Genome editing using versions of the bacterial CRISPR/Cas9 system can
be used to probe the function of selected genes in any organism. Green Listed is
a web-based tool that rapidly designs custom CRISPR screens targeting sets of
genes defined by the user. It could thus be used to design screens targeting for
example all genes differentially expressed during a specific stimuli or all genes
related to a specific pathway or function, as well as to generate targeted
secondary screens following a large-scale screen. Availability and
Implementation: The software, including a demo function as well as explanatory
texts and videos, is available through greenlisted.cmm.ki.se . Contact:
fredrik.wermeling@ki.se.
PMID- 28414856
TI - Radiographic and ultrasonographic findings of the spleen and abdominal lymph
nodes in healthy domestic ferrets.
AB - OBJECTIVE: To describe the radiographic and ultrasonographic characteristics of
the spleen and abdominal lymph nodes in clinically healthy ferrets. MATERIALS AND
METHODS: Fifty-five clinically healthy ferrets were prospectively recruited for
this cross-sectional study. Three-view whole body radiographs and abdominal
ultrasonography were performed on awake (23 out of 55) or sedated (32 out of 55)
ferrets. On radiographs splenic and abdominal lymph node visibility was assessed.
Splenic thickness and echogenicity and lymph node length, thickness,
echogenicity, number and presence of cyst-like changes were recorded. RESULTS:
The spleen was radiographically detectable in all ferrets. On ultrasound the
spleen was hyperechoic to the liver (55 out of 55) and mildly hyperechoic (28 out
of 55), isoechoic (15 out of 55) or mildly hypoechoic (12 out of 55) to the renal
cortices. Mean splenic thickness was 11.80 +/-0.34 mm. Lymph nodes were
radiographically discernible in 28 out of 55 ferrets and included caudal
mesenteric and sublumbar nodes. An average of 9 +/-2 lymph nodes (mean+/-
standard deviation; mode 10) were identified in each ferret using ultrasound. A
single large jejunal lymph node was identified in all ferrets and had a mean
thickness of 5.28 +/- 1.66 mm. For other lymph nodes the mean thickness
measurements plus one standard deviation were less than 4.4 mm (95% confidence
interval: <= 3.72 mm). CLINICAL SIGNIFICANCE: The information provided in this
study may act as a baseline for evaluation of the spleen and lymph nodes in
ferrets.
PMID- 28414857
TI - Association of external cephalic version before term with late preterm birth.
AB - INTRODUCTION: While evidence suggests that beginning an external cephalic version
(ECV) before term (340/7 to 366/7 weeks) compared with after term may be
associated with an increase in late preterm birth (340/7 to 366/7 weeks), it
remains unknown what might account for this risk. The objective of the present
study is to further investigate the association between ECV before term and late
preterm birth. MATERIAL AND METHODS: Secondary analysis of data collected from
the international, multicenter Early ECV trials. We evaluated the relation
between ECV exposure and late preterm birth (340/7 to 366/7 weeks), as well as
whether additional risk factors for preterm birth (such as maternal age, height,
body mass index, parity, placental location, and perinatal mortality rate)
moderated this relation. Generalized linear mixed methods were used to account
for center effect and adjust for covariates. RESULT: Among 1765 women with breech
pregnancies and without a prior preterm birth, 749 (42.4%) received at least one
ECV before term. Exposure to an ECV before term was not associated significantly
independently with odds of preterm birth. However, placenta location moderated
the association between early ECV exposure and late preterm birth. The odds of
preterm birth in women who were exposed to an ECV before term and who also had an
anterior placenta were doubled (OR 2.05; 95% CI 1.12-3.71; p = 0.02). CONCLUSION:
In a large cohort of women without known risks for preterm birth, those with an
anterior placenta who undergo an ECV before term constitute a subgroup at
particular risk for late preterm birth.
PMID- 28414858
TI - Keratoacanthoma-Like Growths of Incontinentia Pigmenti Successfully Treated with
Intralesional Methotrexate.
AB - We report the case of a 17-year-old girl with incontinentia pigmenti who
developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented
patches on her left leg. Biopsy demonstrated an endoexophytic nodule with
irregular invaginations of keratinizing squamous epithelium and a central keratin
filled crater, consistent with keratoacanthoma-like lesions of incontinentia
pigmenti. The tumors were successfully treated with intralesional methotrexate.
PMID- 28414859
TI - Source-receptor probability of atmospheric long-distance dispersal of viruses to
Israel from the eastern Mediterranean area.
AB - Viruses that affect the health of humans and farm animals can spread over long
distances via atmospheric mechanisms. The phenomenon of atmospheric long-distance
dispersal (LDD) is associated with severe consequences because it may introduce
pathogens into new areas. The introduction of new pathogens to Israel was
attributed to LDD events numerous times. This provided the motivation for this
study which is aimed to identify all the locations in the eastern Mediterranean
that may serve as sources for pathogen incursion into Israel via LDD. This aim
was achieved by calculating source-receptor relationship probability maps. These
maps describe the probability that an infected vector or viral aerosol, once
airborne, will have an atmospheric route that can transport it to a distant
location. The resultant probability maps demonstrate a seasonal tendency in the
probability of specific areas to serve as sources for pathogen LDD into Israel.
Specifically, Cyprus' season is the summer; southern Turkey and the Greek islands
of Crete, Karpathos and Rhodes are associated with spring and summer; lower Egypt
and Jordan may serve as sources all year round, except the summer months. The
method used in this study can easily be implemented to any other geographic
region. The importance of this study is the ability to provide a climatologically
valid and accurate risk assessment tool to support long-term decisions regarding
preparatory actions for future outbreaks long before a specific outbreak occurs.
PMID- 28414860
TI - Persistent visual loss in dengue fever due to outer retinal damage.
PMID- 28414861
TI - Management of necrotising fasciitis secondary to abdominal liposuction using a
combination of surgery, hyperbaric oxygen and negative pressure wound therapy in
a patient with burn scars.
AB - Liposuction is the one of the most frequently performed cosmetic operations and
usually has an easy recovery, with a reportedly low overall complication rate.
Here, we report the case of a 60-year-old woman with type II diabetes mellitus
and a previous burn injury of the abdomen who underwent abdominal liposuction and
subsequently developed necrotising fasciitis. Following radical debridement,
systemic antibiotic administration, negative pressure wound therapy and
hyperbaric oxygen therapy, the wound healed completely. This case demonstrates
the success of the combination treatment and highlights the need for clinicians
to be aware of the risk of serious complications in selected patients.
PMID- 28414862
TI - Editorial Perspective: Longitudinal research in autism - introducing the concept
of 'chronogeneity'.
AB - Autism Spectrum Disorder (ASD or autism) is a heterogeneous neurodevelopmental
disorder. We are now at a critical juncture in autism research where we have the
knowledge base and expertise to begin to think about studies that view
heterogeneity, not as 'statistical noise' that can be 'accounted for' using data
reduction techniques (such as group trajectories), but rather as 'informative
variance' that can help form a more precise and dynamic picture of autism. In
this Editorial we coin a new term and introduce the concept of 'chronogeneity'
for the study of autism heterogeneity in relation to the dimension of time
(chrono). Using examples of ongoing research and analytical advances we build the
case for the potential utility of the concept of 'chronogeneity' and argue that a
refined approach to the longitudinal investigation of autism (and other
neurodevelopmental disorders) may move us closer to more precise and adaptive
models of care for the children and youth affected by these disorders.
PMID- 28414863
TI - Commentary: On the importance of looking at nonlinearity and developmental
effects - a reflection on Flom et al. (2017).
AB - By examining both linear and curvilinear associations between mental development
and activity level, the study by Flom et al. (Journal of Child Psychology and
Psychiatry, 2017) highlights the importance of going beyond linear associations
in psychological fields of research. Results from Flom et al. (Journal of Child
Psychology and Psychiatry, 2017) also raise interesting questions for future
research. First, studies should look at variables that may explain the
associations between activity level and mental development, such as self
regulation and attention. Second, longitudinal changes in the strength of the
association between activity level and mental development should be examined to
determine when this association is at its strongest. Finally, longitudinal
research looking at bidirectional effects is needed to confirm the direction of
the associations between activity level and mental development. Answers to these
questions will allow the identification of the best targets and developmental
periods for interventions to take place.
PMID- 28414864
TI - Editorial: Finding the silver lining: incorporating resilience and adaptiveness
into studies of psychopathology.
AB - The editor muses about studies that might complement and enhance current
etiologic studies of psychopathology, many of which focus on monotonically
increasing maladaptative outcomes in response to increasing levels of
risk/vulnerability. More meaningful and consistent considerations of the
resilience counterfactual (e.g., Why are some youth with a given neural deficit
unaffected? Why are some youth exposed to a given adversity unaffected?) should
strengthen our causal inferences. We might also more frequently test for U-shaped
associations with outcome (e.g., Does level of psychopathology predict
deleterious outcomes in a dose-response fashion, or is the association
curvilinear whereby moderate predict good outcomes?). In line with the latter, we
might also more frequently consider the adaptive value of the disorder in
evolutionary terms (e.g., Why is this disorder still part of the human
repertoire? What might be its adaptive value for the species?).
PMID- 28414865
TI - Transvaginal sonography in the diagnosis of deep infiltrating endometriosis: A
review.
AB - This review summarizes the current evidence regarding the diagnostic accuracy of
sonography (US) in women with deep infiltrating endometriosis (DIE). It is well
known that transvaginal ultrasound (TVUS) can detect ovarian endometriomas with a
high degree of sensitivity. In recent years, US has also been used to detect DIE.
In the hands of an experienced sonologist, the sensitivity and specificity of
TVUS in the detection of DIE is comparable to those of MRI. TVUS can eliminate
the need for an MRI in the majority of patients and reduce the need for
diagnostic laparoscopy, proving to be an important tool in preoperative planning.
(c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:313-318, 2017.
PMID- 28414867
TI - Basic-education mexican teachers' knowledge of biotechnology and attitudes about
the consumption of genetically modified foods.
AB - Over the past few years, a new research field has emerged, focusing on the social
scientific criteria for the study of opinions toward genetically modified foods
(GMFs), since these may be limiting factors for the success or failure of these
products. Basic education is the first step in the Mexican education system, and
teachers may wield an outsized influence on the attitudes and preferences of
children, prospective future consumers of these products. To better understand
the current state of knowledge of biotechnology issues and opinions toward the
consumption of GMF of Mexican teachers, a questionnaire was distributed, and 362
Mexican teachers of basic education responded. The survey included questions
about the benefits and risks of consuming GMF. The mean percentage of teachers
expressing knowledge of a given topic in biotechnology was 50%. More than 60% of
teachers believed that GMFs would be useful in preventing world hunger, while
39.2% considered GMF to be hazards for future generations. Although 47.0%
reported not having enough knowledge about these topics, almost all (90.3%)
respondents expressed an interest and willingness to learn about biotechnology.
In light of the fact that teachers of basic education represent the first and
potentially most lasting stage in the education of young children, this survey
establishes the urgent need to develop strategies to improve the scientific
knowledge of teachers and to facilitate decision making and the promotion of
scientific and technological advances for their students. (c) 2017 by The
International Union of Biochemistry and Molecular Biology, 45(5):396-402, 2017.
PMID- 28414866
TI - Characterizing the outcomes of metastatic papillary renal cell carcinoma.
AB - Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly
characterized in the era of targeted therapy. A total of 5474 patients with
metastatic renal cell carcinoma (mRCC) in the International mRCC Database
Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between
clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type
I and type II papillary patients (n = 30 and n = 165, respectively). Overall
survival (OS), progression-free survival (PFS), and overall response rate (ORR)
favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard
ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were
detected between type I and II PRCC in this limited dataset. The median OS for
type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P =
0.096). The IMDC prognostic model was able to stratify pRCC patients into
favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor
risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even
after controlling for IMDC prognostic factors. The IMDC prognostic model was able
to effectively stratify pRCC patients.
PMID- 28414868
TI - Protective Effects of Diallyl Sulfide Against Ethanol-Induced Injury in Rat
Adipose Tissue and Primary Human Adipocytes.
AB - BACKGROUND: Alcohol consumption is the fourth leading cause of death and
disability worldwide. Several cellular pathways contribute to alcohol-mediated
tissue injury. Adipose tissue apart from functioning as an endocrine organ
secretes several hormones and cytokines known as adipokines that are known to
play a significant role in alcohol-induced tissue damage. This study was designed
to test the efficacy of diallyl sulfide (DAS) in regulating the alcohol-induced
outcomes on adipose tissue. METHODS: Male Wistar rats were fed with 36% Lieber
DeCarli liquid diet containing ethanol (EtOH) for 4 weeks. Control rats were pair
fed with isocaloric diet containing maltodextrin instead of EtOH. During the last
week of feeding protocol, the EtOH-fed rat group was given 200 mg/kg body weight
of DAS through diet. We also studied DAS effect on isolated human primary
adipocytes. Viability of human primary adipocytes on DAS treatment was assessed
by MTT assay. Malondialdehyde (MDA), a marker of oxidative stress, was measured
by HPLC and the thiobarbituric acid method. Expression of inflammatory genes and
lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory
gene expression was studied by ELISA. RESULTS: Our study results showed that DAS
could alleviate EtOH-induced expression levels of proinflammatory and endoplasmic
reticulum (ER) stress genes and improve adipose tissue mass and adipocyte
morphology in male Wistar rats fed Lieber-DeCarli diet containing 6% EtOH.
Further, we showed that DAS reduced the expression of lipogenic genes and
improved lipid accumulation and adipocyte mass in human primary adipocytes
treated with EtOH. Subsequently, we also showed that oxidative stress, as
measured by the changes in MDA levels, was reduced in both male Wistar rats and
human primary adipocytes treated with EtOH plus DAS. CONCLUSIONS: Our study
results prove that DAS is effective in ameliorating EtOH-induced damage to
adipose tissue as evidenced by the reduction brought about by DAS in oxidative
stress, ER stress, and proinflammatory gene expression levels. DAS treatment also
regulated lipogenic gene expression levels, thereby reducing free fatty acid
release. In conclusion, this study has clinical implications with respect to
alcohol-induced adipose tissue injury among alcohol users.
PMID- 28414869
TI - Zygomaticomaxillary suture maturation: A predictor of maxillary protraction? Part
I - A classification method.
AB - OBJECTIVE: The aim of this study was to present a method of classifying the
maturational level of the zygomaticomaxillary sutures (ZMSs). METHODS: Cone-beam
CT (CBCT) images from 74 subjects (5.6-58.4 years) were examined to define the
radiographic stages of ZMS maturation. Five stages of maturation of the ZMS were
identified and defined: Stage A-uniform high-density sutural line, with no or
little interdigitation; Stage B-scalloped appearance of the high-density sutural
line; Stage C-two parallel, scalloped, high-density lines, separated in some
areas by small low-density spaces; Stage D-fusion in the inferior portion of the
suture; and Stage E-complete fusion. Intra- and inter-examiner agreements were
evaluated by weighted kappa tests. RESULTS: The intra- and inter-examiners
reproducibility values demonstrated substantial to almost perfect agreement. No
fusion of ZMSs was observed in patients up to 10 years of age. From 10 to 15
years, all maturational stages were identified. After 15 years of age, the
majority of patients showed fusion of ZMSs. CONCLUSIONS: The classification of
ZMS maturation using CBCT is a reliable method that allows the assessment of the
morphology of the ZMSs in the individual patient.
PMID- 28414871
TI - Effect of platelet-rich plasma on orthodontic tooth movement in dogs.
AB - OBJECTIVES: To evaluate the effect of platelet-rich plasma (PRP) on the rate of
orthodontic tooth movement. METHODS: The sample comprised six skeletally mature
male mongrel dogs. The maxillary second premolar in each dog was extracted
bilaterally. PRP was prepared and injected around the first premolar in one
randomly selected maxillary quadrant while the other quadrant served as the
control. Coil springs (150 g) were used to distalize the first premolars for 63
days using TAD as anchorage. RESULTS: Total maxillary tooth movement was
significantly faster on the experimental than on the control side. CONCLUSION:
Local injection of PRP in the present animal study resulted in accelerated
orthodontic tooth movement with no obvious clinical or microscopic side effects.
PMID- 28414870
TI - Three-dimensional skeletal mandibular changes associated with Herbst appliance
treatment.
AB - OBJECTIVES: Three-dimensional evaluation of skeletal mandibular changes following
Herbst appliance treatment. SETTING AND SAMPLE POPULATION: Retrospective case
control study, based on a sample size calculation. Twenty-five pubertal patients
treated with Herbst appliance (HAG), and 25 matched Class II patients who
received other non-orthopaedic dental treatments (CG). MATERIAL AND METHODS:
Three-dimensional models were generated from pre-treatment (T0) and post
treatment (T1) cone beam computed tomograms. Volumetric registration on the
cranial base was used to assess mandibular displacement; volumetric regional
registration was performed to evaluate mandibular growth. Quantitative
measurements of X, Y, Z and 3D Euclidian changes, and also qualitative
visualization by colour-mapping and semi-transparent overlays were obtained.
RESULTS: Downward displacement of the mandible was observed in both HAG and CG
(2.4 mm and 1.5 mm, respectively). Significant forward displacement of the
mandible was observed in the HAG (1.7 mm). HAG showed greater 3D superior and
posterior condylar growth than the CG (3.5 mm and 2.0 mm, respectively). Greater
posterior growth of the ramus was noted in the HAG than in CG. CONCLUSIONS:
Immediately after Herbst therapy, a significant mandibular forward displacement
was achieved, due to increased bone remodelling of the condyles and rami compared
to a comparison group. Three-dimensional changes in the direction and magnitude
of condylar growth were observed in Herbst patients.
PMID- 28414872
TI - A scoping review of outcomes related to orthodontic treatment measured in cleft
lip and palate.
AB - The aim of this study was to identify and summarize the outcomes measured in
orthodontic studies of children with cleft lip and/or palate. The objectives were
to categorize the outcomes into pre-determined domains and to explore whether any
domains were under-represented. Electronic databases and grey literature were
searched until December 2016 to identify all studies of orthodontic treatment
interventions in children and adolescents with cleft lip and palate. Abstracts
and subsequently eligible full-text articles were screened independently and in
duplicate by two reviewers. All reported outcome measures were identified and
categorized into six predetermined outcome domains. The search identified 833
abstracts. The majority of studies did not assess orthodontic interventions and
were therefore not eligible for inclusion. Consequently, following screening 71
eligible articles were retrieved in full, of which 40 met the inclusion criteria.
Morphological features of malocclusion were measured in 27 studies (68%) and
adverse effects of orthodontic treatment in 10 (25%). Functional status (n=4;
10%), physical consequences of malocclusion (n=3; 7.5%), quality of life (n=3;
7.5%) and health resource utilization (n=2; 5%) were rarely considered.
Relatively few studies concerning patients with cleft lip and palate focused on
orthodontic interventions. Most of the identified outcomes were concerned with
measuring morphological treatment-related changes and do not reflect patient
perspectives.
PMID- 28414873
TI - Influence of pharyngeal airway respiration pressure on Class II mandibular
retrusion in children: A computational fluid dynamics study of inspiration and
expiration.
AB - OBJECTIVES: To examine the influence of negative pressure of the pharyngeal
airway on mandibular retraction during inspiration in children with nasal
obstruction using the computational fluid dynamics (CFD) method. SETTING AND
SAMPLE POPULATION: Sixty-two children were divided into Classes I, II (mandibular
retrusion) and III (mandibular protrusion) malocclusion groups. MATERIAL AND
METHODS: Cone-beam computed tomography data were used to reconstruct three
dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was
simulated using CFD to calculate nasal resistance and pharyngeal airway pressure
during inspiration and expiration. RESULTS: Nasal resistance of the Class II
group was significantly higher than that of the other two groups, and
oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was
larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups
(P<.001). The oropharyngeal airway inspiration-expiration pressure difference in
the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and
Class III (0.68 Pa) groups (P=.006). CONCLUSION: Large negative inspiratory
pharyngeal airway pressure due to nasal obstruction in children with Class II
malocclusion may be related to their retrognathia.
PMID- 28414874
TI - In vitro evaluation of the influence of velocity on sliding resistance of
stainless steel arch wires in a self-ligating orthodontic bracket.
AB - INTRODUCTION: Of the variables used by in vitro studies of resistance to sliding
(RS) in orthodontics, sliding velocity (SV) of the wire is often the one farthest
from its clinical counterpart. We investigated whether velocity influences the RS
at values approximating the orthodontic movement. METHODS: A SS self-ligating
bracket with a NiTi clip was fixed onto a custom-made model. Different shaped
orthodontic SS wires of four sizes and two types (round, 0.020" and 0.022";
rectangular, 0.016"*0.022" and 0.017"*0.025") were tested using an Instron(r)
testing machine. Wires were pulled at four velocities (1*10-2 mm/s, 1*10-3
mm/s, 1*10-4 mm/s, 1*10-5 mm/s). Shapiro-Wilk test was used to evaluate the
normal distribution of the data; two-way ANOVA was performed to compare means in
the RS with wire characteristics and SV. Significance level was set at P<.05.
RESULTS: RS was higher for rectangular wires, and for those with larger
diameters. Lower SV was associated with lower RS, with wire type and size having
an interaction effect. The RS relatively to SV can be represented as: RS ?
alpha[ln(SV)]+beta, where alpha and beta are constants. CONCLUSIONS: At very low
SV and low normal forces, SV influences the RS of SS archwires in orthodontic
brackets, and the proportionality is logarithmic. Although respecting these
parameters in vitro is challenging, quantitative evaluations of RS should be
carried out at clinically relevant velocities if aiming at translational
application in the clinical scenario.
PMID- 28414875
TI - Royal Australasian College of Surgeons 86th Annual Scientific Congress, Adelaide,
Australia, 8-12 May 2017.
PMID- 28414876
TI - Are extremely preterm born children with autism the victims of too much isolation
in the incubator?
PMID- 28414877
TI - Accelerated point of muscle deoxygenation during the 20-m shuttle run test.
AB - This study examined whether the point of accelerated deoxygenation of active
muscle occurs during the 20-m shuttle run test (20mSRT) and, if so, whether it is
associated with exercise performance in the test. Twenty-nine male subjects
performed the 20mSRT, and concentration changes in oxyhaemoglobin (DeltaOxy-Hb)
and deoxyhaemoglobin (DeltaDeoxy-Hb) in the m. vastus lateralis were measured
using a portable near-infrared spectroscopy device. The difference between the
relative concentration changes in DeltaOxy-Hb and DeltaDeoxy-Hb (Delta[Oxy-Hb -
Deoxy-Hb]) was regarded as the muscle oxygenation index. Group-averaged Delta[Oxy
Hb - Deoxy-Hb] showed progressive decrease during the test. However, among the
individuals, we found an accelerated point of decrease in Delta[Oxy-Hb - Deoxy
Hb] in 20 subjects, which revealed that the laps at the accelerated point
correlated with the total laps (r = 0.78). These results demonstrate that the
accelerated deoxygenation of active muscle occurs during the 20mSRT, but not in
all cases. Our findings also indicate that if the accelerated point of muscle
deoxygenation occurs, the timing of its appearance is related to 20mSRT
performance.
PMID- 28414878
TI - Do outdoor workers know their risk of NMSC? Perceptions, beliefs and preventive
behaviour among farmers, roofers and gardeners.
AB - BACKGROUND: Non-melanoma skin cancer (NMSC) was officially recognized in 2015 as
an occupational disease for outdoor workers in Germany. Together with the
enormous socioeconomic impact of NMSC, this has led to the continuous demand of
evidence-based prevention. However, studies assessing the perceptions and beliefs
along with risk behaviour of outdoor workers as an essential prerequisite for
prevention are rare. OBJECTIVE: To assess perceptions, beliefs, barriers, risk
and preventive behaviours towards non-melanoma skin cancer among different
outdoor groups as a basis for the development of sustainable prevention
programmes. PATIENTS AND METHODS: Cross-sectional study among outdoor workers of
three different occupational groups (farmer, gardener, roofer) using a 20
question online survey on NMSC awareness, risk and preventive behaviours.
RESULTS: Between March and April 2016, 353 outdoor workers participated in the
study. Of these, 153 (43.4%) reported never to use sunscreen during work. Wearing
headgear and long pants were the most common sun protection measures. Poor use of
sunscreen was more likely in males and farmers. A low perceived skin cancer risk
was significantly associated with poor use of sunscreen, long-sleeved shirts,
sunglasses and headgear. CONCLUSIONS: Despite great evidence on NMSC risk in
outdoor professions throughout the literature, high-risk groups in fact are not
yet aware of the topic. Sustainable target group-oriented awareness prevention
programmes are needed to lower the immense burden of NMSC.
PMID- 28414880
TI - A new class of ribozyme from hepatitis B virus.
AB - In this issue, Chakraborty and Ghosh present initial in vitro data indicating a
53-base part of the hepatitis B virus (HBV) epsilon region is a ribozyme with
unusual properties. Self-cleavage first occurred at the HBV non-canonical
polyadenylation signal UAUAAA and the "centre bulge" of the epsilon region,
releasing a ribozyme. The released ribozyme then acted as a new class of trans
cleaving ribozyme cleaving other RNAs.
PMID- 28414882
TI - The effect of a faith community nurse network and public health collaboration on
hypertension prevention and control.
AB - BACKGROUND: As part of the Association of State and Territorial Health Official's
Million Hearts State Learning Collaborative in 2014 and 2015, Washington County,
Maryland formed a collaboration between the local health department, health
system and faith community nurse network to address the undiagnosed and
uncontrolled hypertension in the county. OBJECTIVES: Data were analyzed to
determine the effect of a faith community nursing intervention of teaching blood
pressure self-monitoring and coaching blood pressure and lifestyle changes in the
at-risk and hypertensive population. METHODS: Thirty-nine faith community nurses
offered a 3-month blood pressure self-monitoring and coaching intervention in
2014 and 2015 to 119 participants. A secondary data analysis using a repeated
measure ANOVA to assess the differences in pre- and post-intervention systolic
and diastolic blood pressure readings and a paired t-test to compare pre- and
post-lifestyle scores was completed. RESULTS: A total of 109 participants
completed the program and were included in the analysis and were showing
decreased blood pressure readings and improved lifestyle satisfaction scores in
six out of seven areas across the program period. CONCLUSION: Coaching by faith
community nurses creates an environment of sustained support that can promote
improved lifestyles and blood pressure changes over time.
PMID- 28414883
TI - Temperature and rainfall interact to control carbon cycling in tropical forests.
AB - Tropical forests dominate global terrestrial carbon (C) exchange, and recent
droughts in the Amazon Basin have contributed to short-term declines in
terrestrial carbon dioxide uptake and storage. However, the effects of longer
term climate variability on tropical forest carbon dynamics are still not well
understood. We synthesised field data from more than 150 tropical forest sites to
explore how climate regulates tropical forest aboveground net primary
productivity (ANPP) and organic matter decomposition, and combined those data
with two existing databases to explore climate - C relationships globally. While
previous analyses have focused on the effects of either temperature or rainfall
on ANPP, our results highlight the importance of interactions between temperature
and rainfall on the C cycle. In cool forests (< 20 degrees C), high rainfall
slowed rates of C cycling, but in warm tropical forests (> 20 degrees C) it
consistently enhanced both ANPP and decomposition. At the global scale, our
analysis showed an increase in ANPP with rainfall in relatively warm sites,
inconsistent with declines in ANPP with rainfall reported previously. Overall,
our results alter our understanding of climate - C cycle relationships, with high
precipitation accelerating rates of C exchange with the atmosphere in the most
productive biome on earth.
PMID- 28414885
TI - Nasopharyngeal tumor developing in a 36-year-old man following radiation for a
childhood meningioma.
PMID- 28414886
TI - 50-year-old man with a falcine mass.
PMID- 28414887
TI - 61-year-old man with chronic expansile sellar mass.
PMID- 28414888
TI - Models of human adamantinomatous craniopharyngioma tissue: Steps toward an
effective adjuvant treatment.
AB - Even though ACP is a benign tumor, treatment is challenging because of the
tumor's eloquent location. Today, with the exception of surgical intervention and
irradiation, further treatment options are limited. However, ongoing molecular
research in this field provides insights into the pathways involved in ACP
pathogenesis and reveal a plethora of druggable targets. In the next step,
appropriate models are essential to identify the most suitable and effective
substances for clinical practice. Primary cell cultures in low passages provide a
proper and rapid tool for initial drug potency testing. The patient-derived
xenograft (PDX) model accommodates ACP complexity in that it shows respect to the
preserved architecture and similar histological appearance to human tumors and
therefore provides the most appropriate means for analyzing pharmacological
efficacy. Nevertheless, further research is needed to understand in more detail
the biological background of ACP pathogenesis, which provides the identification
of the best targets in the hierarchy of signaling cascades. ACP models are also
important for the continuous testing of new targeting drugs, to establish
precision medicine.
PMID- 28414889
TI - Proteomics in pediatric cystic craniopharyngioma.
AB - Adamantinomatous craniopharyngioma (ACP) is still often burdened by a poor
prognosis in children as far as the risk of recurrence and the quality of life
are concerned. Therefore, many efforts are now dedicated to investigate the
molecular characteristics of this tumor aiming at finding new therapeutic
options. ACP is prevalently a cystic lesion so that an increasing number of
researches are focused on the analysis of its cystic content. In the present
article, the main results of the current proteomic analysis (PA) on the ACP fluid
are summarized. Both "bottom-up" and "top-down" approaches have been utilized. In
the bottom-up approach, proteins and peptides are enzymatically or chemically
digested prior to liquid chromatography and mass spectrometry analyses. The
bottom-up approach pointed out several proteins of the inflammation (namely,
alpha2-HS-glycoprotein, alpha1-antichymotrypsin and apolipoproteins) as possibly
involved in the genesis and growth of the cystic component of ACP. The top-down
strategy analyzes proteins and peptides in the intact state, making it
particularly suitable for the identification of peptides and low molecular weight
proteins and for the characterization of their possible isoforms and post
translational modifications. The top-down approach disclosed the presence of the
thymosin beta family. Thymosin beta4, in particular, which is involved in the
cytoskeleton organization and migration of several tumors, could play a role in
the progression of ACP. Finally, PA was utilized to investigate alterations in
cyst fluid character after treatment with interferon-alpha. The analyzed samples
showed a progressive reduction of the levels of alpha-defensins (proteins
involved in the inflammatory-mediated response) after the intracystic injection
of interferon-alpha, thus reinforcing the hypothesis that inflammation
contributes to ACP cyst pathogenesis. Additional studies on the solid component
of ACP are still necessary to further validate the previous results and to
identify possible markers for targeted therapy.
PMID- 28414890
TI - Corrigendum.
PMID- 28414891
TI - Genetically engineered mouse models of craniopharyngioma: an opportunity for
therapy development and understanding of tumor biology.
AB - Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar
region in childhood. Two genetically engineered mouse models have been developed
and are giving valuable insights into ACP biology. These models have identified
novel pathways activated in tumors, revealed an important function of paracrine
signalling and extended conventional theories about the role of organ-specific
stem cells in tumorigenesis. In this review, we summarize these mouse models,
what has been learnt, their limitations and open questions for future research.
We then discussed how these mouse models may be used to test novel therapeutics
against potentially targetable pathways recently identified in human ACP.
PMID- 28414892
TI - A 19-year-old male with a well-demarcated parieto-occipital mass.
PMID- 28414893
TI - Impact of viral hepatitis aetiology on survival outcomes in hepatocellular
carcinoma: A large multicentre cohort study.
AB - While HBV and HCV are risk factors for HCC, uncertainty exists as to whether
these viral infections have prognostic significance in HCC. Thus, we compared the
overall survival of patients with HBV, HCV and nonviral HCC, and evaluated
whether the presence of HBV and HCV predicts patient outcomes. We conducted a
multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals
between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour
characteristics and patient outcomes were obtained from hospital databases,
computer records and the Victorian Death Registry. Survival outcomes were
compared between HBV, HCV and nonviral hepatitis cases and predictors of survival
determined using Cox proportional hazards regression. There were 1436 new HCC
cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV
30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral
HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On
multivariate analysis, independent risk factors for survival included HCC
aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and
serum creatinine and albumin. After adjusting for these and method of detection,
HBV remained an independent predictor of improved overall survival when compared
to both nonviral (HR 0.60%, 95% CI 0.35-0.98; P=.03) and HCV-related HCC (HR
0.51%, 95% CI 0.30-0.85; P=.01). In this large multicentre study, HBV is
independently associated with improved overall survival compared with HCV and
nonviral-related HCC. Further studies are needed to determine the underlying
factor(s) responsible.
PMID- 28414894
TI - Effects of BEAT Cancer randomized physical activity trial on subjective memory
impairments in breast cancer survivors.
PMID- 28414895
TI - The Impact of CT Perfusion Threshold on Predicted Viable and Nonviable Tissue
Volumes in Acute Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Perfusion imaging is used for patient selection in
clinical practice and trials. Postprocessing and definitions of tissue viability
are nevertheless not standardized. We compared the lesion volumes generated with
two well-recognized perfusion tissue definitions in a single-center phase 2
thrombolysis study. METHODS: We analyzed perfusion imaging data from the
Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study
using two popular tissue viability thresholds (ischemic core definition: (1)
cerebral blood volume < 2.0 mL/100 g-1 or (2) relative cerebral blood flow < 40%
that of the contralesional hemisphere and relative delay time >2 seconds;
penumbra definitions: (1) mean transit time > 145% of contralesional hemisphere
or (2) relative delay time < 2 seconds). We compared volumes of core and
penumbra, mismatch ratio, percentage, and volume of penumbra salvaged at 24
hours. RESULTS: We included 73 (tenecteplase = 36, alteplase = 37) patients who
had analyzable perfusion lesions at baseline. Significant differences were found
in core volumes using the two thresholds (33 +/- 37 mL vs. 26 +/- 32 mL, P <
.001), as was mismatch ratio (2.5 +/- .9 vs. 4.2 +/- 3.7, P < 0.001). The volume
of penumbra salvaged at 24 hours (30 +/- 19 mL vs. 35 +/- 26 mL, P = .043)
differed significantly, although the percentages of penumbra salvaged did not (P
= .2). No difference was found between the two thrombolytic agents in the
percentages of penumbra salvaged using either threshold. CONCLUSION: Two commonly
used tissue definitions generated significantly different lesion volumes and
mismatch ratios. Threshold selection may have significant impact on patient
selection for trials or reperfusion therapies.
PMID- 28414896
TI - NK cells in self-limited HCV infection exhibit a more extensively differentiated,
but not memory-like, repertoire.
AB - Natural killer (NK) cells have long been thought of as a purely innate immune
cell population, but increasing reports have described developmental and
functional qualities of NK cells that are commonly associated with cells of the
adaptive immune system. Of these features, the ability of NK cells to acquire
functional qualities associated with immunological memory and continuous
differentiation resulting in the formation of specific NK cell repertoires has
recently been highlighted in viral infection settings. By making use of a unique
cohort of monitored, at-risk intravenous drug users in this study, we were able
to dissect the phenotypic and functional parameters associated with NK cell
differentiation and NK cell memory in patients 3 years after acute HCV infection
and either the subsequent self-clearance or progression to chronicity. We
observed increased expression of cytolytic mediators and markers CD56bright and
NKp46+ of NK cells in patients with chronic, but not self-limited HCV infection.
Patients with a self-limited infection expressed higher levels of differentiation
associated markers CD57 and KIRs, and lower levels of NKG2A. A more extensively
differentiated NK cell phenotype is associated with self-clearance in HCV
patients, while the NK cells of chronic patients exhibited more naive and
effector NK cell phenotypic and functional characteristics. The identification of
these distinct NK cell repertoires may shed light on the role NK cells play in
determining the outcome of acute HCV infections, and the underlying immunological
defects that lead to chronicity.
PMID- 28414897
TI - Rapid drink challenge and multiple rapid swallowing: Reproducibility of
esophageal function assessment.
PMID- 28414898
TI - Does my patient still have reflux when ppi therapy does not work?
AB - Gastroesophageal reflux disease (GERD) is a common condition around the world.
The management of this disease is less than satisfying given complexity of
patient presentation and suboptimal diagnostic testing when employed for those
poorly responsive to acid suppressive therapy. In this mini review, we discuss
some new strategies employed for patients with suspected GERD to better
understand disease pathophysiology. We compare the strategies and outline a
clinically relevant approach in this difficult group of patients.
PMID- 28414899
TI - Comparison of sedation by intranasal dexmedetomidine and oral chloral hydrate for
pediatric ophthalmic examination.
AB - BACKGROUND AND AIM: Pediatric ophthalmic examinations can be conducted under
sedation either by chloral hydrate or by dexmedetomidine. The objective was to
compare the success rates and quality of ophthalmic examination of children
sedated by intranasal dexmedetomidine vs oral chloral hydrate. METHODS: One
hundred and forty-one children aged from 3 to 36 months (5-15 kg) scheduled to
ophthalmic examinations were randomly sedated by either intranasal
dexmedetomidine (2 MUg.kg-1 , n = 71) or oral chloral hydrate (80 mg.kg-1 , n =
70). The primary endpoint was successful sedation to complete the examinations
including slit-lamp photography, tonometry, anterior segment analysis, and
refractive error inspection. The secondary endpoints included quality of eye
position, intraocular pressure, onset time, duration of examination, recovery
time, discharge time, any side effects during examination, and within 48 h after
discharge. RESULTS: Sixty-one children were sedated by dexmedetomidine with a
success rate of 85.9%, which is significantly higher than that by chloral hydrate
(64.3%) [OR 3.39, 95% CI: 1.48-7.76, P = 0.003]. Furthermore, children in the
dexmedetomidine group displayed better eye position in anterior segment analysis
than in chloral hydrate group median difference. All children displayed stable
hemodynamics and none suffered hypoxemia in both groups. Oral chloral hydrate
induced higher percentages of vomiting and altered bowel habit after discharge
than dexmedetomidine. CONCLUSIONS: Intranasal dexmedetomidine provides more
successful sedation and better quality of ophthalmic examinations than oral
chloral hydrate for small children.
PMID- 28414900
TI - Precision Templated Bottom-Up Multiprotein Nanoassembly through Defined Click
Chemistry Linkage to DNA.
AB - We demonstrate an approach that allows attachment of single-stranded DNA (ssDNA)
to a defined residue in a protein of interest (POI) so as to provide optimal and
well-defined multicomponent assemblies. Using an expanded genetic code system,
azido-phenylalanine (azF) was incorporated at defined residue positions in each
POI; copper-free click chemistry was used to attach exactly one ssDNA at
precisely defined residues. By choosing an appropriate residue, ssDNA conjugation
had minimal impact on protein function, even when attached close to active sites.
The protein-ssDNA conjugates were used to (i) assemble double-stranded DNA
systems with optimal communication (energy transfer) between normally separate
groups and (ii) generate multicomponent systems on DNA origami tiles, including
those with enhanced enzyme activity when bound to the tile. Our approach allows
any potential protein to be simply engineered to attach ssDNA or related
biomolecules, creating conjugates for designed and highly precise multiprotein
nanoscale assembly with tailored functionality.
PMID- 28414901
TI - Assembled Suprastructures of Inorganic Chiral Nanocrystals and Hierarchical
Chirality.
AB - Chiral organizations ubiquitously exist in biomaterials via hierarchical assembly
of chiral molecules, but assembly of chiral inorganic nanocrystals (NCs) has been
lacking. Recent development of cinnabar HgS NCs that can possess precisely
engineered chirality originating from both atomic lattice and morphology offers
an emerging class of inorganic building blocks to explore their hierarchical
assembly. Two different forms of suprastructures, collinear chains and
propellers, have been achieved with various chiral HgS NC building blocks via
distinct assembly mechanisms. The chiroptical responses of suprastructures are
further evaluated both experimentally and theoretically, and are found to
uniquely depend on intrinsic chirality of building blocks and their coupling. Our
study therefore opens up a gateway to new assembled inorganic suprastructures
with desired chiroptical response for wide-ranging functionalities and
applications by bottom-up modular approach.
PMID- 28414902
TI - Tuning Chemistry and Topography of Nanoengineered Surfaces to Manipulate Immune
Response for Bone Regeneration Applications.
AB - Osteoimmunomodulation has informed the importance of modulating a favorable
osteoimmune environment for successful materials-mediated bone regeneration.
Nanotopography is regarded as a valuable strategy for developing advanced bone
materials, due to its positive effects on enhancing osteogenic differentiation.
In addition to this direct effect on osteoblastic lineage cells, nanotopography
also plays a vital role in regulating immune responses, which makes it possible
to utilize its immunomodulatory properties to create a favorable osteoimmune
environment. Therefore, the aim of this study was to advance the applications of
nanotopography with respect to its osteoimmunomodulatory properties, aiming to
shed further light on this field. We found that tuning the surface chemistry
(amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm)
significantly modulated the osteoimmune environment, including changes in the
expression of inflammatory cytokines, osteoclastic activities, and osteogenic,
angiogenic, and fibrogenic factors. The generated osteoimmune environment
significantly affected the osteogenic differentiation of bone marrow stromal
cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most
promising outcome. This study demonstrated that the osteoimmunomodulation could
be manipulated via tuning the chemistry and nanotopography, which implied a
valuable strategy to apply a "nanoengineered surface" for the development of
advanced bone biomaterials with favorable osteoimmunomodulatory properties.
PMID- 28414903
TI - Nanopore Logic Operation with DNA to RNA Transcription in a Droplet System.
AB - This paper describes an AND logic operation with amplification and transcription
from DNA to RNA, using T7 RNA polymerase. All four operations, (0 0) to (1 1),
with an enzyme reaction can be performed simultaneously, using four-droplet
devices that are directly connected to a patch-clamp amplifier. The output RNA
molecule is detected using a biological nanopore with single-molecule
translocation. Channel current recordings can be obtained using the enzyme
solution. The integration of DNA logic gates into electrochemical devices is
necessary to obtain output information in a human-recognizable form. Our method
will be useful for rapid and confined DNA computing applications, including the
development of programmable diagnostic devices.
PMID- 28414904
TI - In Silico Prediction of Chemicals Binding to Aromatase with Machine Learning
Methods.
AB - Environmental chemicals may affect endocrine systems through multiple mechanisms,
one of which is via effects on aromatase (also known as CYP19A1), an enzyme
critical for maintaining the normal balance of estrogens and androgens in the
body. Therefore, rapid and efficient identification of aromatase-related
endocrine disrupting chemicals (EDCs) is important for toxicology and environment
risk assessment. In this study, on the basis of the Tox21 10K compound library,
in silico classification models for predicting aromatase binders/nonbinders were
constructed by machine learning methods. To improve the prediction ability of the
models, a combined classifier (CC) strategy that combines different independent
machine learning methods was adopted. Performances of the models were measured by
test and external validation sets containing 1336 and 216 chemicals,
respectively. The best model was obtained with the MACCS (Molecular Access
System) fingerprint and CC method, which exhibited an accuracy of 0.84 for the
test set and 0.91 for the external validation set. Additionally, several
representative substructures for characterizing aromatase binders, such as
ketone, lactone, and nitrogen-containing derivatives, were identified using
information gain and substructure frequency analysis. Our study provided a
systematic assessment of chemicals binding to aromatase. The built models can be
helpful to rapidly identify potential EDCs targeting aromatase.
PMID- 28414905
TI - Application of an Acyl-CoA Ligase from Streptomyces aizunensis for Lactam
Biosynthesis.
AB - epsilon-Caprolactam and delta-valerolactam are important commodity chemicals used
in the manufacture of nylons, with millions of tons produced annually. Biological
production of these highly valued chemicals has been limited due to a lack of
enzymes that cyclize omega-amino fatty acid precursors to corresponding lactams
under ambient conditions. In this study, we demonstrated production of these
chemicals using ORF26, an acyl-CoA ligase involved in the biosynthesis of ECO
02301 in Streptomyces aizunensis. This enzyme has a broad substrate spectrum and
can cyclize 4-aminobutyric acid into gamma-butyrolactam, 5-aminovaleric acid into
delta-valerolactam and 6-aminocaproic acid into epsilon-caprolactam. Recombinant
E. coli expressing ORF26 produced valerolactam and caprolactam when 5
aminovaleric acid and 6-aminocaproic acid were added to the culture medium. Upon
coexpressing ORF26 with a metabolic pathway that produced 5-aminovaleric acid
from lysine, we were able to demonstrate production of delta-valerolactam from
lysine.
PMID- 28414906
TI - Protecting Silicon Film Anodes in Lithium-Ion Batteries Using an Atomically Thin
Graphene Drape.
AB - Silicon (Si) shows promise as an anode material in lithium-ion batteries due to
its very high specific capacity. However, Si is highly brittle, and in an effort
to prevent Si from fracturing, the research community has migrated from the use
of Si films to Si nanoparticle based electrodes. However, such a strategy
significantly reduces volumetric energy density due to the porosity of Si
nanoparticle electrodes. Here we show that contrary to conventional wisdom, Si
films can be stabilized by two strategies: (a) anchoring the Si films to a carbon
nanotube macrofilm (CNM) current collector and (b) draping the films with a
graphene monolayer. After electrochemical cycling, the graphene-coated Si films
on CNM resembled a tough mud-cracked surface in which the graphene capping layer
suppresses delamination and stabilizes the solid electrolyte interface. The
graphene-draped Si films on CNM exhibit long cycle life (>1000 charge/discharge
steps) with an average specific capacity of ~806 mAh g-1. The volumetric capacity
averaged over 1000 cycles of charge/discharge is ~2821 mAh cm-3, which is 2 to 5
times higher than what is reported in the literature for Si nanoparticle based
electrodes. The graphene-draped Si anode could also be successfully cycled
against commercial cathodes in a full-cell configuration.
PMID- 28414907
TI - Cell Isolation and Recovery Using Hollow Glass Microspheres Coated with
Nanolayered Films for Applications in Resource-Limited Settings.
AB - Established cell isolation and purification techniques such as fluorescence
activated cell sorting (FACS), isolation through magnetic micro/nanoparticles,
and recovery via microfluidic devices have limited application as disposable
technologies appropriate for point-of-care use in remote areas where lab
equipment as well as electrical, magnetic, and optical sources are restricted. We
report a simple yet effective method for cell isolation and recovery that
requires neither specialized lab equipment nor any form of power source.
Specifically, self-floating hollow glass microspheres were coated with an
enzymatically degradable nanolayered film and conjugated with antibodies to allow
both fast capture and release of subpopulations of cells from a cell mixture.
Targeted cells were captured by the microspheres and allowed to float to the top
of the hosting liquid, thereby isolating targeted cells. To minimize nonspecific
adhesion of untargeted cells and to enhance the purity of the isolated cell
population, an antifouling polymer brush layer was grafted onto the nanolayered
film. Using the EpCAM-expressing cancer cell line PC-3 in blood as a model
system, we have demonstrated the isolation and recovery of cancer cells without
compromising cell viability or proliferative potential. The whole process takes
less than 1 h. To support the rational extension of this platform technology, we
introduce extensive characterization of the critical design parameters: film
formation and degradation, grafting with a poly(ethylene glycol) (PEG) sheath,
and introducing functional antibodies. Our approach is expected to overcome
practical hurdles and provide viable targeted cells for downstream analyses in
resource-limited settings.
PMID- 28414908
TI - Experimental-Computational Study of Carbon Nanotube Effects on Mitochondrial
Respiration: In Silico Nano-QSPR Machine Learning Models Based on New Raman
Spectra Transform with Markov-Shannon Entropy Invariants.
AB - The study of selective toxicity of carbon nanotubes (CNTs) on mitochondria (CNT
mitotoxicity) is of major interest for future biomedical applications. In the
current work, the mitochondrial oxygen consumption (E3) is measured under three
experimental conditions by exposure to pristine and oxidized CNTs (hydroxylated
and carboxylated). Respiratory functional assays showed that the information on
the CNT Raman spectroscopy could be useful to predict structural parameters of
mitotoxicity induced by CNTs. The in vitro functional assays show that the
mitochondrial oxidative phosphorylation by ATP-synthase (or state V3 of
respiration) was not perturbed in isolated rat-liver mitochondria. For the first
time a star graph (SG) transform of the CNT Raman spectra is proposed in order to
obtain the raw information for a nano-QSPR model. Box-Jenkins and perturbation
theory operators are used for the SG Shannon entropies. A modified RRegrs
methodology is employed to test four regression methods such as multiple linear
regression (LM), partial least squares regression (PLS), neural networks
regression (NN), and random forest (RF). RF provides the best models to predict
the mitochondrial oxygen consumption in the presence of specific CNTs with R2 of
0.998-0.999 and RMSE of 0.0068-0.0133 (training and test subsets). This work is
aimed at demonstrating that the SG transform of Raman spectra is useful to encode
CNT information, similarly to the SG transform of the blood proteome spectra in
cancer or electroencephalograms in epilepsy and also as a prospective
chemoinformatics tool for nanorisk assessment. All data files and R object models
are available at https://dx.doi.org/10.6084/m9.figshare.3472349 .
PMID- 28414909
TI - Examining the Effect of Exchange-Correlation Approximations in First-Principles
Dynamics Simulation of Interfacial Charge Transfer.
AB - We examine the extent to which the exchange-correlation (XC) approximation
influences modeling interfacial charge transfer using fewest-switches surface
hopping (FSSH) simulations within the single-particle description. A
heterogeneous interface between a lithium ion and an extended boron-nitride sheet
was considered here, being an extreme case in which wave function localization
and energy level alignments are highly sensitive to the XC approximation. The
PBE0 hybrid XC approximation yields nonadiabatic couplings (NACs) that are
significantly smaller than the values obtained from the PBE-GGA approximation by
an order of magnitude for localized electronic states. This difference between
the two XC functionals for the calculated NACs was found to derive mainly from
the wave function characteristics rather than from the lattice movement although
first-principles molecular dynamics trajectories, along which NACs are obtained,
differ noticeably between the two XC functionals. Using the NACs and single
particle energy level alignments at different levels of theory, FSSH simulations
were performed to model the electron transfer dynamics at the interface. The
electron transfer time scale was found to vary as much as, but not more than, 1
order of magnitude. The time scale was found to be quite sensitive to both NACs
and energy level alignments. While the order of magnitude consistency for the
charge transfer rate is encouraging even for this rather extreme model of
heterojunction interface, continued advancement in electronic structure methods
is required for quantitatively accurate determination of the transfer rate.
PMID- 28414910
TI - Efficient Criterion To Evaluate Linear Response Theory in Optical Transitions.
AB - The role of the Gaussian statistics on the solvation dynamics upon the photon
excitation of the chromophore is deeply explored. The linear response theory for
the fluorescence Stokes shift is investigated. An analytical formulism is
presented to recast Stokes shift into the contributions of the equilibrium time
correlation functions of the solute-solvent interactions on the excited-state
surface, and the latter is further reformed and depicted by the time relaxation
of the moment. As the first application of the formulism in the molecular
dynamics simulations, it is verified that the efficiency of the linear response
theory relies on the Gaussian characteristics of the dominant moments in terms of
the Stokes shift, which is identified by the same relaxation dynamics between
those moments and the linear order one. The comparisons between the above
observations on the linearity of Stokes shift and the explanations in the
literature are discussed. The key finding is the development of explicit
criterion to measure the appropriateness of applying linear response theory.
PMID- 28414911
TI - A Platform for Analysis of Nanoscale Liquids with an Array of Sensor Devices
Based on Two-Dimensional Material.
AB - Analysis of nanoscale liquids, including wetting and flow phenomena, is a
scientific challenge with far reaching implications for industrial technologies.
We report the conception, development, and application of an integrated platform
for the experimental characterization of liquids at the nanometer scale. The
platform combines the functionalities of a two-dimensional electronic array of
sensor devices with in situ application of highly sensitive optical
microspectroscopy and atomic force microscopy. We demonstrate the performance
capabilities of the platform with an embodiment based on an array of optically
transparent graphene sensors. The application of electronic and optical sensing
in the platform allows for differentiating between liquids electronically, for
determining a liquid's molecular fingerprint, and for monitoring surface wetting
dynamics in real time. In order to explore the platform's sensitivity limits, we
record topographies and optical spectra of individual, spatially isolated sessile
oil emulsion droplets having volumes of less than ten attoliters. The results
demonstrate that integrated measurement functionalities based on two-dimensional
materials have the potential to push lab-on-chip based analysis from the
microscale to the nanoscale.
PMID- 28414912
TI - Observation of Photovoltaic Action from Photoacid-Modified Nafion Due to Light
Driven Ion Transport.
AB - Replacing passive ion-exchange membranes, like Nafion, with membranes that use
light to drive ion transport would allow membranes in photoelectrochemical
technologies to serve in an active role. Toward this, we modified
perfluorosulfonic acid ionomer membranes with organic pyrenol-based photoacid
dyes to sensitize the membranes to visible light and initiate proton transport.
Covalent modification of the membranes was achieved by reacting Nafion sulfonyl
fluoride poly(perfluorosulfonyl fluoride) membranes with the photoacid 8
hydroxypyrene-1,3,6-tris(2-aminoethylsulfonamide). The modified membranes were
strongly colored and maintained a high selectivity for cations over anions.
Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and
ion-exchange measurements together provided strong evidence of covalent bond
formation between the photoacids and the polymer membranes. Visible-light
illumination of the photoacid-modified membranes resulted in a maximum power
producing ionic photoresponse of ~100 MUA/cm2 and ~1 mV under 40 Suns equivalent
excitation with 405 nm light. In comparison, membranes that did not contain
photoacids and instead contained ionically associated RuII-polypyridyl
coordination compound dyes, which are not photoacids, exhibited little-to-no
photoeffects (~1 MUA/cm2). These disparate photocurrents, yet similar yields for
nonradiative excited-state decay from the photoacids and the RuII dyes, suggest
temperature gradients were not likely the cause of the observed photovoltaic
action from photoacid-modified membranes. Moreover, spectral response
measurements supported that light absorption by the covalently bound photoacids
was required in order to observe photoeffects. These results represent the first
demonstration of photovoltaic action from an ion-exchange membrane and offer
promise for supplementing the power demands of electrochemical processes with
renewable sunlight-driven ion transport.
PMID- 28414913
TI - Life-Cycle Assessment Harmonization and Soil Science Ranking Results on Food
Waste Management Methods.
AB - This study reviewed 147 life cycle studies, with 28 found suitable for
harmonizing food waste management methods' climate and energy impacts. A total of
80 scientific soil productivity studies were assessed to rank management method
soil benefits. Harmonized climate impacts per kilogram of food waste range from
0.20 kg of carbon dioxide equivalents (CO2e) for anaerobic digestion (AD) to 0.38
kg of CO2e for landfill gas-to-energy (LFGTE). Aerobic composting (AC) emits
0.10 kg of CO2e. In-sink grinding (ISG) via a food-waste disposer and flushing
for management with other sewage at a wastewater treatment plant emits 0.10 kg of
CO2e. Harmonization reduced climate emissions versus nonharmonized averages.
Harmonized energy impacts range from -0.32 MJ for ISG to 1.14 MJ for AC. AD at
0.27 MJ and LFGTE at 0.40 MJ fall in between. Rankings based on soil studies show
AC first for carbon storage and water conservation, with AD second. AD first for
fertilizer replacement, with AC second, and AC and AD tied for first for plant
yield increase. ISG ranks third and LFGTE fourth on all four soil-quality and
productivity indicators. Suggestions for further research include developing soil
benefits measurement methods and resolving inconsistencies in the results between
life-cycle assessments and soil science studies.
PMID- 28414914
TI - Designing Uniquely Addressable Bio-orthogonal Synthetic Scaffolds for DNA and RNA
Origami.
AB - Nanotechnology and synthetic biology are rapidly converging, with DNA origami
being one of the leading bridging technologies. DNA origami was shown to work
well in a wide array of biotic environments. However, the large majority of
extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus
severely limiting its future applicability as a bio-orthogonal nanotechnology
platform. In this paper we present the design of biologically inert (i.e., "bio
orthogonal") origami scaffolds. The synthetic scaffolds have the additional
advantage of being uniquely addressable (unlike biologically derived ones) and
hence are better optimized for high-yield folding. We demonstrate our fully
synthetic scaffold design with both DNA and RNA origamis and describe a protocol
to produce these bio-orthogonal and uniquely addressable origami scaffolds.
PMID- 28414915
TI - Tethered Fluorogen Assay to Visualize Membrane Apposition in Living Cells.
AB - We describe proof-of-concept for a novel approach for visualizing regions of
close apposition between the surfaces of living cells. A membrane-anchored
protein with high affinity for a chemical ligand is expressed on the surface of
one set of cells, and the cells are co-cultured with a second set of cells that
express a membrane-anchored fluorogen-activating protein (FAP). The co-cultured
cells are incubated with a bivalent reagent composed of fluorogen linked to the
high-affinity ligand, with the concentration of the bivalent reagent chosen to be
less than the binding constant for the FAP-fluorogen pair but greater than the
binding constant for the ligand-high-affinity protein pair. In these conditions,
strong FAP signal is observed only in regions of close proximity between
membranes of the two classes of cell, where high local concentration of fluorogen
favors binding to the FAP.
PMID- 28414916
TI - Quercetin Remodels the Tumor Microenvironment To Improve the Permeation,
Retention, and Antitumor Effects of Nanoparticles.
AB - Our previous work demonstrated that Wnt16 expression in cisplatin-damaged tumor
associated fibroblasts is a key factor contributing to cisplatin resistance in
malignancies. Natural antifibrotic compounds with low toxicities are promising
candidates to downregulate Wnt16 expression, improving the antitumor effect of
cisplatin nanoparticles. Upon screening several natural chemicals, we found that
a dietary flavonoid, quercetin, significantly suppresses Wnt16 expression in
activated fibroblasts. To facilitate drug delivery, we have prepared a targeted
lipid/calcium/phosphate nanoparticle formulation consisting of a prodrug of
quercetin, i.e., quercetin phosphate, with a high loading efficiency (26.6% w/w).
This quercetin nanoparticle with a particle size of around 35 nm significantly
improved the bioavailability and metabolic stability of the parent quercetin.
Quercetin phosphate is released from the nanoparticles and converted back to the
parent quercetin under physiological conditions. Following systemic
administration of quercetin phosphate nanoparticles, a significant downregulation
in Wnt16 expression was observed and further yielded a synergistic antitumor
effect with cisplatin nanoparticles in a stroma-rich bladder carcinoma model. The
alpha-SMA-positive fibroblast and collagen within the tumor decreased
significantly after combination treatment. This suggests that the remodeling of
the tumor microenvironment induced by quercetin plays a critical role in
promoting the synergy. Indeed, our data further confirmed that quercetin
phosphate alone significantly remodeled the tumor microenvironment and increased
the penetration of second-wave nanoparticles into the tumor nests. Collectively,
quercetin phosphate nanoparticles may be a safe and effective way to improve
therapeutic treatment for desmoplastic tumors.
PMID- 28414918
TI - Frogs host faecal bacteria typically associated with humans.
AB - Tree frogs commonly access drinking water tanks; this may have human health
implications. Although amphibians might not be expected to host mammalian faecal
indicator bacteria (FIB), it is possible that they may have human FIB on their
skin after exposure to human waste. We collected faeces and skin wash from green
tree frogs (Litoria caerulea) from a natural environment, a suburban site, and a
suburban site near a creek occasionally contaminated with sewage effluent. We
used molecular techniques to test for FIB that are routinely used to indicate
human faecal contamination. Enterococci colonies were isolated from both faecal
and skin wash samples, and specific markers (Enterococcus faecium and Bacteroides
thetaiotaomicron) were found in frog faeces, demonstrating that these markers are
not human- or mammalian-specific. Bacteroides thetaiotaomicron was detected in
frogs from both natural and urban sites, but E. faecium was only associated with
the sewage impacted site.
PMID- 28414917
TI - Epidemiology of Knee Sprains in Youth, High School, and Collegiate American
Football Players.
AB - CONTEXT: Variations in knee-sprain incidence among competition levels are
unclear but may help inform prevention strategies in American football players.
OBJECTIVE: To describe the epidemiology of knee sprains in youth, high school,
and collegiate football players. DESIGN: Descriptive epidemiology study.
SETTING: Injury and athlete-exposure (AE) data were collected from 3 injury
surveillance programs at the youth, high school, and collegiate competition
levels. PATIENTS OR OTHER PARTICIPANTS: Data from 310 youth, 184 high school,
and 71 collegiate football team-seasons were collected during the 2012 through
2014 seasons. MAIN OUTCOME MEASURE(S): Knee-sprain rates and risks were
calculated for each competition level. Injury rate ratios (IRRs) and risk ratios
(RRs) compared knee-sprain rates by competition level. Injury proportion ratios
(IPRs) compared differences in surgery needs, recurrence, injury mechanism, and
injury activity by competition level. RESULTS: Knee-sprain rates in youth, high
school, and collegiate football were 0.16/1000 AEs, 0.25/1000 AEs, and 0.69/1000
AEs, respectively. Knee-sprain rates increased as the competition level increased
(high school versus youth: IRR = 1.60; 95% confidence interval [CI] = 1.12, 2.30;
collegiate versus high school: IRR = 2.73; 95% CI = 2.38, 3.96). Knee-sprain risk
was highest in collegiate (4.3%), followed by high school (2.0%) and youth (0.5%)
athletes. Knee-sprain risk increased as the competition level increased (high
school versus youth: RR = 3.73; 95% CI = 2.60, 5.34; collegiate versus high
school: RR = 2.14; 95% CI = 1.83, 2.51). Collegiate football had the lowest
proportion of knee sprains that were noncontact injuries (collegiate versus
youth: IPR = 0.54; 95% CI = 0.31, 0.95; collegiate versus high school: IPR =
0.59; 95% CI = 0.44, 0.79) and the lowest proportion that occurred while being
tackled (collegiate versus youth: IPR = 0.44; 95% CI = 0.26, 0.76; collegiate
versus high school: IPR = 0.71; 95% CI = 0.51, 0.98). CONCLUSIONS: Knee-sprain
incidence was highest in collegiate football. However, level-specific variations
in the distributions of knee sprains by injury activity may highlight the need to
develop level-specific policies and prevention strategies that ensure safe sports
play.
PMID- 28414919
TI - Functional characterization of an N-terminally-truncated mitochondrial porin
expressed in Neurospora crassa.
AB - Mitochondrial porin, which forms voltage-dependent anion-selective channels
(VDAC) in the outer membrane, can be folded into a 19-beta-stranded barrel. The N
terminus of the protein is external to the barrel and contains alpha-helical
structure. Targeted modifications of the N-terminal region have been assessed in
artificial membranes, leading to different models for gating in vitro. However,
the in vivo requirements for gating and the N-terminal segment of porin are less
well-understood. Using Neurospora crassa porin as a model, the effects of a
partial deletion of the N-terminal segment were investigated. The protein,
DeltaN2-12porin, is assembled into the outer membrane, albeit at lower levels
than the wild-type protein. The resulting strain displays electron transport
chain deficiencies, concomitant expression of alternative oxidase, and decreased
growth rates. Nonetheless, its mitochondrial genome does not contain any
significant mutations. Most of the genes that are expressed in high levels in
porin-less N. crassa are expressed at levels similar to that of wild type or are
slightly increased in DeltaN2-12porin strains. Thus, although the N-terminal
segment of VDAC is required for complete function in vivo, low levels of a
protein lacking part of the N terminus are able to rescue some of the defects
associated with the absence of porin.
PMID- 28414920
TI - Sharing Data and Materials in Psychological Science.
PMID- 28414921
TI - Distinct distribution patterns of proteobacterial nirK- and nirS-type
denitrifiers in the Yellow River estuary, China.
AB - Denitrification is considered to be the critical process in removing reactive
nitrogen in estuarine ecosystems. In the present study, the abundance, diversity,
and community structure of nirK- and nirS-type denitrifiers were compared in
sediments from the Yellow River estuary. Quantitative polymerase chain reaction
showed that the 2 types of denitrifiers exhibited different distribution patterns
among the samples, indicating their distinct habitat preference. Phylogenetic
analysis revealed that most of the sequences from clusters I, III, IV, and V for
nirK-type denitrifiers were dominant and were distributed at sites where
dissolved oxygen (DO) was lower, and the sequences in the other clusters were
dominant at sites with higher DO. However, there was no spatially heterogeneous
distribution for the nirS-type denitrifier community. Canonical correlation
analysis and correlation analysis demonstrated that the community structure of
nirK was more responsive to environmental factors than was that of nirS.
Inversely, the abundance and alpha-diversity targeting nirS gene could be more
easily influenced by environmental parameters. These findings can extend our
current knowledge about the distribution patterns of denitrifying bacteria and
provide a basic theoretical reference for the dynamics of denitrifying
communities in estuarine ecosystem of China.
PMID- 28414922
TI - Three new active members of the I-OnuI family of homing endonucleases.
AB - In vitro characterization of 3 LAGLIDADG-type homing endonucleases (HEs) (I-CcaI,
I-CcaII, and I-AstI) that belong to the I-OnuI family showed that they are
functional HEs that cleave their respective cognate target sites. These
endonucleases are encoded within group ID introns and appear to be orthologues
that have inserted into 3 different mitochondrial genes: rns, rnl, and cox3. The
endonuclease activity of I-CcaI was tested using various substrates, and its
minimum DNA recognition sequence was estimated to be 26 nt. This set of HEs may
provide some insight into how these types of mobile elements can migrate into new
locations. This study provides additional endonucleases that can be added to the
catalog of currently available HEs that may have various biotechnology
applications.
PMID- 28414923
TI - Determining the True Selectivity Profile of alphav Integrin Ligands Using
Radioligand Binding: Applying an Old Solution to a New Problem.
AB - The arginyl-glycinyl-aspartic acid (RGD) integrin subfamily contains five members
that partner with the alphav subunit: alphavbeta1, alphavbeta3, alphavbeta5,
alphavbeta6, and alphavbeta8. Within the alphav integrins, the epithelially
restricted alphavbeta6 has been identified as playing a key role in the
activation of transforming growth factor beta that is hypothesized to be pivotal
in the development of idiopathic pulmonary fibrosis (IPF). As part of a drug
discovery program to identify a selective alphavbeta6 RGD mimetic for IPF, cell
adhesion and radioligand binding assays were investigated to screen compounds to
determine affinity and alphav integrin selectivity. In this study, a pan-alphav
radioligand was characterized against all the alphav integrins and used to
determine accurate selectivity profiles for literature and novel RGD ligands, as
well as enable an early readout on alphavbeta6 dissociation kinetics. It has been
shown that while cell adhesion offers a high throughput and reliable format for
ranking compounds, there are downsides to this format when comparing selectivity
across alphav integrins. By accurately defining the relationship between these
assay formats, a medicinal chemistry effort has identified novel, high-affinity,
and selective alphavbeta6 RGD mimetics with slow dissociation kinetics, with the
potential to be developed into clinical candidates for IPF.
PMID- 28414924
TI - Vasectomy and Risk of Prostate Cancer: How to Weigh Current Evidence.
PMID- 28414925
TI - Reversion of BRCA1/2 Germline Mutations Detected in Circulating Tumor DNA From
Patients With High-Grade Serous Ovarian Cancer.
AB - Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous
ovarian cancer (HGSC) are associated with favorable responses to chemotherapy.
However, secondary intragenic (reversion) mutations that restore protein function
lead to clinically significant rates of acquired resistance. The goal of this
study was to determine whether reversion mutations could be found in an unbiased
manner in circulating cell-free DNA (cfDNA) to predict treatment response in
HGSC. Patients and Methods Plasma and tumor samples were obtained from 30
patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were
ascertained: patients with a malignancy before undergoing primary HGSC debulking
surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and
plasma samples were available for most patients (24 of 30). Targeted amplicon,
next-generation sequencing was performed using primers that flanked germline
mutations, whose design did not rely on prior knowledge of reversion sequences.
Results Five patients were identified with intragenic mutations predicted to
restore BRCA1/2 open reading frames, including two patients with multiple
independent reversion alleles. Reversion mutations were only detected in tumor
samples from patients with recurrent disease (five of 16) and only in cfDNA from
patients with a tumor-detected reversion (three of five). Findings from a rapid
autopsy of a patient with multiple independent reversions indicated that
reversion-allele frequency in metastatic sites is an important determinant of
assay sensitivity. Abundance of tumor-derived DNA in total cell-free DNA, as
measured by TP53 mutant allele frequency, also affected assay sensitivity. All
patients with reversions detected in tumor-derived DNA were resistant to platin-
or poly ADP ribose polymerase inhibitor-based chemotherapy. Conclusion Reversion
mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical
utility for predicting chemotherapy response in recurrent HGSC.
PMID- 28414926
TI - Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk
Factors and Scope of the Problem.
AB - Purpose Despite advances in childhood cancer care, some patients die soon after
diagnosis. This population is not well described and may be under-reported.
Better understanding of risk factors for early death and scope of the problem
could lead to prevention of these occurrences and thus better survival rates in
childhood cancer. Methods We retrieved data from SEER 13 registries on 36,337
patients age 0 to 19 years diagnosed with cancer between 1992 and 2011. Early
death was defined as death within 1 month of diagnosis. Socioeconomic status data
for each individual's county of residence were derived from Census 2000. Crude
and adjusted odds ratios and corresponding 95% CIs were estimated for the
association between early death and demographic, clinical, and socioeconomic
factors. Results Percentage of early death in the period was 1.5% (n = 555).
Children with acute myeloid leukemia, infant acute lymphoblastic leukemia,
hepatoblastoma, and malignant brain tumors had the highest risk of early death.
On multivariable analysis, an age younger than 1 year was a strong predictor of
early death in all disease groups examined. Black race and Hispanic ethnicity
were both risk factors for early death in multiple disease groups. Residence in
counties with lower than median average income was associated with a higher risk
of early death in hematologic malignancies. Percentages of early death decreased
significantly over time, especially in hematologic malignancies. Conclusion Risk
factors for early death in childhood cancer include an age younger than 1 year,
specific diagnoses, minority race and ethnicity, and disadvantaged socioeconomic
status. The population-based disease-specific percentages of early death were
uniformly higher than those reported in cooperative clinical trials, suggesting
that early death is under-reported in the medical literature. Initiatives to
identify those at risk and develop preventive interventions should be
prioritized.
PMID- 28414927
TI - Integration of free-hand 3D ultrasound and mobile C-arm cone-beam CT: Feasibility
and characterization for real-time guidance of needle insertion.
AB - This work presents development of an integrated ultrasound (US)-cone-beam CT
(CBCT) system for image-guided needle interventions, combining a low-cost
ultrasound system (Interson VC 7.5MHz, Pleasanton, CA) with a mobile C-arm for
fluoroscopy and CBCT via use of a surgical tracker. Imaging performance of the
ultrasound system was characterized in terms of depth-dependent contrast-to-noise
ratio (CNR) and spatial resolution. US-CBCT system was evaluated in phantom
studies simulating three needle-based procedures: drug delivery, tumor ablation,
and lumbar puncture. Low-cost ultrasound provided flexibility but exhibited
modest CNR and spatial resolution that is likely limited to fairly superficial
applications within a ~10cm depth of view. Needle tip localization demonstrated
target registration error 2.1-3.0mm using fiducial-based registration.
PMID- 28414928
TI - New iminodibenzyl derivatives with anti-leishmanial activity.
AB - Leishmaniasis is an infection caused by protozoa of the genus Leishmania and
transmitted by sandflies. Current treatments are expensive and time-consuming,
involving Sb(V)-based compounds, lipossomal amphotericin B and miltefosine.
Recent studies suggest that inhibition of trypanothione reductase (TR) could be a
specific target in the development of new drugs because it is essential and
exclusive to trypanosomatids. This work presents the synthesis and
characterization of new iminodibenzyl derivatives (dado) with ethylenediamine
(ea), ethanolamine (en) and diethylenetriamine (dien) and their copper(II)
complexes. Computational methods indicated that the complexes were highly
lipophilic. Pro-oxidant activity assays by oxidation of the dihydrorhodamine
(DHR) fluorimetric probe showed that [Cu(dado-ea)]2+ has the highest rate of
oxidation, independent of H2O2 concentration. The toxicity to L. amazonensis
promastigotes and RAW 264,7 macrophages was assessed, showing that dado-en was
the most active new compound. Complexation to copper did not have an appreciable
effect on the toxicity of the compounds.
PMID- 28414929
TI - Association of physical injury and mental health: Results from the national
comorbidity survey- adolescent supplement.
AB - Nonfatal injury is common among adolescents in the U.S., but little is known
about the bi-directional associations between injury and mental health. Utilizing
a nationally representative sample of U.S. adolescents, we examined 1)
associations between lifetime mental health history and subsequent injury; 2)
concurrent associations between injury and mental health; and 3) associations
between injury and subsequent mental disorders. Data were drawn from the National
Comorbidity Survey Replication-Adolescent Supplement (NCS-A), a national survey
of adolescents aged 13 through 17 years (N = 10,123). Twelve-month prevalence of
nonfatal injury requiring medical attention was assessed along with lifetime, 12
month, and 30-day prevalence of DSM-IV depressive, anxiety, behavior, substance
use, and bipolar disorders. We used Poisson regression to examine associations
between 1) lifetime history of mental disorders and 12-month exposure to injury;
2) concurrent associations between 12-month exposure to injury and 12-month
prevalence of mental disorders; and 3) 12-month exposure to injury and 30-day
prevalence of mental disorders. A total of 11.6% of adolescents experienced an
injury requiring medical attention in the year before the survey. Lifetime
history of mental disorders was not associated with past-year injury. Behavior
and bipolar disorders were concurrently associated with past-year injury. Past
year injury occurrence predicted increased risk for past-month anxiety disorders
and decreased risk of past-month depressive disorders. Our findings reveal
reciprocal associations between injury and mental disorders and highlight the
need for systematic assessment, prevention, and treatment of mental disorders
among injured youth.
PMID- 28414930
TI - Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role
of heat-shock protein production.
AB - Current antipsychotics reduce positive symptoms and reverse negative symptoms in
conjunction with cognitive behavioral issues with the goal of restoring impaired
occupational and social functioning. However, limited information is available on
their influence on gliogenesis or their neurogenic properties in adult
schizophrenia brains, particularly on GABAergic interneuron production. In the
present study, we used young adult subventricular zone (SVZ)-derived progenitor
cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and
GABAergic interneuron genesis effects of several kinds of antipsychotics on
changes in differentiation function induced by exposure to the NMDA receptor
antagonist MK-801. We herein demonstrated that antipsychotics promoted or
restored changes in the oligodendrocyte/GABAergic interneuron differentiation
functions of NG2(+) cells induced by the exposure to MK-801, which was considered
to be one of the drug-induced schizophrenia model. We also demonstrated that
antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with
differentiation impairment. The antipsychotics olanzapine, aripiprazole, and
blonanserin, but not haloperidol increased HSP90 levels, which were reduced by
the exposure to MK-801. Our results showed that antipsychotics, particularly
those recently synthesized, exerted similar GABAergic interneuron genesis effects
on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing
cellular HSP production, and also suggest that HSP90 may play a crucial role in
the pathophysiology of schizophrenia and is a key target for next drug
development.
PMID- 28414931
TI - Human adipose tissue levels of persistent organic pollutants and metabolic
syndrome components: Combining a cross-sectional with a 10-year longitudinal
study using a multi-pollutant approach.
AB - We aimed to assess the influence of long-term exposure to POPs on the risk of
metabolic syndrome, combining a cross-sectional with a 10-year longitudinal
follow-up design. Residues of eight POPs were quantified in adipose tissue
samples from 387 participants recruited between 2003 and 2004 in Granada province
(Spain). The outcome ("metabolically compromised") was defined as having >=1
diagnosis of type 2 diabetes, hypertension, hypertriglyceridemia, and/or low HDL
cholesterol. The cross-sectional analysis was conducted in the initial cohort,
while the 10-year longitudinal analysis was conducted in those 154 participants
free of any of the so-mentioned metabolic diseases and classified as
"metabolically healthy" at recruitment. Statistical analyses were performed using
single and multi-pollutant approaches through logistic and Cox regression
analyses with elastic net penalty. After adjusting for confounders, beta
hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB) were independently
associated with an increased risk of being metabolically compromised (unpenalized
ORs=1.17, 95% CI=1.01-1.36 and 1.17, 95% CI=0.99-1.38, respectively). Very
similar results were found in the 10-year longitudinal analysis [HRs=1.28, 95%
CI=1.01-1.61 (beta-HCH); 1.26, 95% CI=1.00-1.59 (HCB)] and were in line with
those obtained using elastic net regression. Finally, when the arithmetic sum of
both compounds was used as independent variable, risk estimates increased to
OR=1.25, 95% CI=1.03-1.52 and HR=1.32, 95% CI=1.02-1.70. Our results suggest that
historical exposure to HCB and beta-HCH is consistently associated with the risk
of metabolic disorders, and that these POPs might be partly responsible for the
morbidity risk traditionally attributed to age and obesity.
PMID- 28414932
TI - Trans-popliteal reflux in limbs with and without deep-vein thrombosis of the same
subject: Cross-sectional study.
PMID- 28414933
TI - Clinically relevant bleeding and thrombotic events in non-cirrhotic splanchnic
vein thrombosis. Long-term follow up.
PMID- 28414934
TI - Blood clot parameters: Thromboelastography and scanning electron microscopy in
research and clinical practice.
AB - BACKGROUND: Clotting parameters are informative of overall haematological
healthiness of an individual. Particularly, clotting parameters can be used as a
measure of the degree of pathology of the coagulation system. Thromboelastography
(TEG) is a well-known technique that is an important point-of-care method, as
well as research method. Scanning electron microscopy (SEM) is a novel research
method, but with possible clinical application. However, there are no clear
standardized guidelines for TEG and SEM result interpretation. MATERIALS AND
METHODS: We have an extensive database of results from TEG of hypercoagulable,
hypocoagulable and healthy whole blood (WB) and platelet poor plasma (PPP). These
results were generated using citrated PPP or WB, followed by the addition of
CaCl2, to initiate clot formation. We also have an extensive and comprehensive
database of thousands of clot micrographs, prepared for SEM. We reanalysed all
our data to compile a user-friendly guideline for TEG and SEM. We also discuss
the effects of different storage times on both WB and PPP. RESULTS: We provide a
quick and informative guide that discusses each TEG parameter, in both WB and
PPP. Increases or decreases in the various parameters are indicative of either
hyper- or hypocoagulability. We also show how hypo- and hypercoagulable clots
look like, compared with healthy clots, using SEM analysis of clots created by
adding thrombin to PPP. CONCLUSION: For optimal and speedy interpretation of a
patient's coagulation status, it is essential for the clinician to make an
informed and precise decision regarding clotting propensity. We believe this
guideline will add to the standardization of TEG parameters, and ultimately
contribute to the treatment of patients. These guidelines will also allow
researchers to standardize their data interpretations and ultimately allow for
the use of a global and inclusive database that might be included in precision
medicine approaches.
PMID- 28414935
TI - cDNA cloning, molecular modeling and docking calculations of L-type lectins from
Swartzia simplex var. grandiflora (Leguminosae, Papilionoideae), a member of the
tribe Swartzieae.
AB - The genus Swartzia is a member of the tribe Swartzieae, whose genera constitute
the living descendants of one of the early branches of the papilionoid legumes.
Legume lectins comprise one of the main families of structurally and
evolutionarily related carbohydrate-binding proteins of plant origin. However,
these proteins have been poorly investigated in Swartzia and to date, only the
lectin from S. laevicarpa seeds (SLL) has been purified. Moreover, no sequence
information is known from lectins of any member of the tribe Swartzieae. In the
present study, partial cDNA sequences encoding L-type lectins were obtained from
developing seeds of S. simplex var. grandiflora. The amino acid sequences of the
S. simplex grandiflora lectins (SSGLs) were only averagely related to the known
primary structures of legume lectins, with sequence identities not greater than
50-52%. The SSGL sequences were more related to amino acid sequences of
papilionoid lectins from members of the tribes Sophoreae and Dalbergieae and from
the Cladratis and Vataireoid clades, which constitute with other taxa, the first
branching lineages of the subfamily Papilionoideae. The three-dimensional
structures of 2 representative SSGLs (SSGL-A and SSGL-E) were predicted by
homology modeling using templates that exhibit the characteristic beta-sandwich
fold of the L-type lectins. Molecular docking calculations predicted that SSGL-A
is able to interact with D-galactose, N-acetyl-D-galactosamine and alpha-lactose,
whereas SSGL-E is probably a non-functional lectin due to 2 mutations in the
carbohydrate-binding site. Using molecular dynamics simulations followed by
density functional theory calculations, the binding free energies of the
interaction of SSGL-A with GalNAc and alpha-lactose were estimated as -31.7 and
47.5 kcal/mol, respectively. These findings gave insights about the carbohydrate
binding specificity of SLL, which binds to immobilized lactose but is not
retained in a matrix containing D-GalNAc as ligand.
PMID- 28414936
TI - East Urals Radioactive Trace: Dose-dependent functional-metabolic effects in the
myocardium of the pygmy wood mouse (Apodemus uralensis) taking into account
population size.
AB - The population dynamics, radiometric data and biochemical parameters
(concentrations of total lipids, proteins, DNA and RNA, activity of succinate
dehydrogenase, glucose phosphate isomerase and catalase, as well as lipid
peroxidation level) in the myocardium of the pygmy wood mouse (Apodemus uralensis
Pall., 1811) inhabiting the area of the East Urals Radioactive Trace (EURT) were
analyzed. The functional-metabolic radiation effects as a result external and
internal exposure to 137Cs and 90Sr (unweighted total dose rate 0.04-0.5 mGy/day)
are characterized by a reduction in lipid catabolism, mitochondrial oxidation and
antioxidant defense, as well as the activation of anaerobic glycolysis as well as
the protein-synthesizing and genetic apparatus. The data indicate the low
efficiency of cell energy production and allow us to state that compensatory
myocardial hypertrophy can improve myocardial contractile function. The level of
the functional-metabolic response in pygmy wood mice in the EURT area increased
with increasing whole-body radiation dose rate and was more pronounced with a
large pygmy wood mouse population size. The harmful effects (cardiac
decompensation stage) of synergies resulting from non-radiation and radiation
factors manifest after population abundance above 30 ind./100 trap-day and a
radiation burden above 0.1 mGy/day.
PMID- 28414937
TI - Accessibility of tertiary hospitals in Finland: A comparison of administrative
and normative catchment areas.
AB - The determination of an appropriate catchment area for a hospital providing
highly specialized (i.e. tertiary) health care is typically a trade-off between
ensuring adequate client volumes and maintaining reasonable accessibility for all
potential clients. This may pose considerable challenges, especially in sparsely
inhabited regions. In Finland, tertiary health care is concentrated in five
university hospitals, which provide services in their dedicated catchment areas.
This study utilizes Geographic Information Systems (GIS), together with grid
based population data and travel-time estimates, to assess the spatial
accessibility of these hospitals. The current geographical configuration of the
hospitals is compared to a normative assignment, with and without capacity
constraints. The aim is to define optimal catchment areas for tertiary hospitals
so that their spatial accessibility is as equal as possible. The results indicate
that relatively modest improvements can be achieved in accessibility by using
normative assignment to determine catchment areas.
PMID- 28414938
TI - Violence against children perpetrated by peers: A cross-sectional school-based
survey in Uganda.
AB - Violence against children by peers is a global public health problem. We aimed to
assess factors associated with peer violence victimization among primary school
children in Uganda. We conducted multilevel multivariable logistic regression
analyses of cross-sectional data from 3706 primary students in 42 Ugandan primary
schools. Among primary school students, 29% and 34% had ever experienced physical
and emotional violence perpetrated by their peers, respectively. Factors strongly
associated with both physical and emotional violence were similar and
overlapping, and included exposure to interparental violence, having an attitude
supportive of violence against children from school staff, not living with
biological parents, working for payment, and higher SDQ score. However, we found
that younger age, sharing sleeping area with an adult and achieving a higher
educational performance score, were specifically associated with physical
violence. On the other hand, being female, walking to school, reporting
disability and eating one meal on the previous day, were particularly associated
with emotional violence. Interventions to reduce peer violence should focus on
family contexts, school environments and those with poor socio-economic status
may need extra support.
PMID- 28414939
TI - Reporting rates of child sexual abuse in Indigenous communities in two Australian
jurisdictions.
AB - Child sexual abuse is a significant problem in many Indigenous communities; there
is also evidence of chronic under-reporting of this crime. This study aimed to
compare reporting rates between Indigenous and non-Indigenous cases of child
sexual abuse across two Australian jurisdictions. Datasets comprising child
sexual abuse reports from the Police Information Management Systems of the two
jurisdictions were used to calculate reporting rates, and to compare case
characteristics and case progression. Results indicated that the reporting rate
for child sexual abuse of Indigenous children was between two and four times that
of non-Indigenous children. In the Indigenous cases, the second jurisdiction had
lower reporting rates than the first jurisdiction. Further analysis of the
Indigenous cases only found that cases in the second jurisdiction were more
severe, more likely to have a forensic interview, and more likely for the suspect
to be charged, than in the first jurisdiction. However, there were no significant
differences in conviction rates between the two jurisdictions. Differences
observed in severity and case progression suggest that the lower reporting rates
observed in the second jurisdiction may be due to comparatively high levels of
under-reporting, rather than lower actual levels of child sexual abuse. In
conclusion, reporting rates of child sexual abuse can be better understood when
further information, such as case characteristics and case progression rates, is
available.
PMID- 28414940
TI - Sexual reoffense trajectories with youths in the child welfare system.
AB - The present study sought to determine whether the persistence of problematic
sexualized behaviors (PSBs) committed by boys in the Massachusetts child welfare
system would lend support to previous taxonomies categorizing offenders as early
onset/life course-persistent, adolescence-onset/adolescence-limited, or childhood
limited in their offending behavior. We examined the persistence of PSBs in a
male sample (N=638; age range: two to 17), using a retrospective longitudinal
archival design. Procedures involved a comprehensive archival review of records
from the Department of Children and Families. Subsamples were established by
trifurcating the sample based on age at the time of the boys' first documented
PSB, resulting in age cohorts reflecting early childhood (age two to seven),
middle childhood (age eight to 11), and preadolescence/adolescence (age 12-17).
Results supported the hypothesis that youths who first exhibited PSBs in early
childhood would produce higher sexual reoffense rates during each of three follow
up windows (i.e., three years, five years, and seven years) than youths who first
exhibited such behaviors in middle childhood, or preadolescence/adolescence
(p<0.01 for all group contrasts). Findings supported the distinctions of several
taxonomies classifying youthful offenders in the juvenile justice system. Abuse
reactivity, coping ability, and vulnerability to iatrogenic intervention effects
are considered as some of many possible contributing factors.
PMID- 28414941
TI - Endo-symbiont mediated synthesis of gold nanobactericides and their activity
against human pathogenic bacteria.
AB - Synthesis of gold nanobactericides (AuNBs) were achieved by treating 1mM
chloroaurate with cell free supernatant of Aneurinibacillus migulanus. Formation
of AuNBs was initially was monitored with change in colour to ruby red. Further
confirmation was assessed with UV-visible spectra with maximum absorption
occurring at 510nm. Transmission electron microscopy (TEM) analysis revealed the
polydispersity of AuNBs with size distribution ranging from 10 to 60nm with an
average size of 30nm. Crystalline nature was studied using X-ray diffraction
which exhibited characteristic peaks indexed to Bragg's reflection at 2theta
angle which confers (111), (200), (220), and (311) planes suggesting AuNBs were
face-centred cubic. Fourier transform infrared spectroscopy (FTIR) analysis
revealed absorption peaks occurring at 3341cm-1, 1635cm-1 and 670cm-1 which
corresponds to functional groups attributing to synthesis. The antibacterial
efficacy of AuNBs was tested against selective human pathogenic bacteria and
activity was measured as zone of inhibition by using disc and well diffusion.
Bactericidal activity was interpreted with standard antibiotics gentamicin and
kanamycin. Micro broth dilution assay expressed the minimal concentration of
AuNBs to inhibit the growth of test pathogens. Highest activity was observed
against Pseudomonas aeruginosa (MTCC 7903) with 21.00+/-0.57mm compared to other
pathogens. The possible mode of action of AuNBs on DNA was carried out with in
vitro assay as preliminary test against pathogenic DNA isolated from P.
aeruginosa. Further studies will be interesting enough to reveal the exact
interactive mechanism of AuNBs with DNA. Overall study contributes towards
biogenic synthesis of AuNBs as one of the alternative in combating drug resistant
pathogens.
PMID- 28414942
TI - Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae
(Danio rerio).
AB - 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of
the mevalonic acid pathway and is required for cholesterol biosynthesis and the
synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the
downstream products of this pathway including the biosynthesis of decaprenyl
pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show
that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV;
Lipitor) exhibited movement alterations and reduced whole body tissue metabolism.
The ATV-inhibition of HMGCR function altered transcript abundance of muscle
atrophy markers (atrogen-1, murf) and the mitochondrial biogenesis marker (pgc
1alpha). Furthermore, ATV-induced reduction in larval response to tactile stimuli
was reversed with treatment of CoQ10. Together, the implication of our results
contributes to the understanding of the mechanisms of action of the statin
induced damage in this model fish species.
PMID- 28414943
TI - Ship-in-a-bottle CMPO in MIL-101(Cr) for selective uranium recovery from aqueous
streams through adsorption.
AB - Mesoporous MIL-101(Cr) is used as host for a ship-in-a-bottle type adsorbent for
selective U(VI) recovery from aqueous environments. The acid-resistant cage-type
MOF is built in-situ around N,N-Diisobutyl-2-(octylphenylphosphoryl)acetamide
(CMPO), a sterically demanding ligand with high U(VI) affinity. This one-step
procedure yields an adsorbent which is an ideal compromise between homogeneous
and heterogeneous systems, where the ligand can act freely within the pores of
MIL-101, without leaching, while the adsorbent is easy separable and reusable.
The adsorbent was characterized by XRD, FTIR spectroscopy, nitrogen adsorption,
XRF, ADF-STEM and EDX, to confirm and quantify the successful encapsulation of
the CMPO in MIL-101, and the preservation of the host. Adsorption experiments
with a central focus on U(VI) recovery were performed. Very high selectivity for
U(VI) was observed, while competitive metal adsorption (rare earths, transition
metals...) was almost negligible. The adsorption capacity was calculated at
5.32mg U/g (pH 3) and 27.99mg U/g (pH 4), by fitting equilibrium data to the
Langmuir model. Adsorption kinetics correlated to the pseudo-second-order model,
where more than 95% of maximum uptake is achieved within 375min. The adsorbed
U(VI) is easily recovered by desorption in 0.1M HNO3. Three adsorption/desorption
cycles were performed.
PMID- 28414944
TI - Direct and indirect electrochemical reduction prior to a biological treatment for
dimetridazole removal.
AB - Two different electrochemical reduction processes for the removal of
dimetridazole, a nitroimidazole-based antibiotic, were examined in this work. A
direct electrochemical reduction was first carried out in a home-made flow cell
in acidic medium at potentials chosen to minimize the formation of amino
derivatives and then the formation of azo dimer. Analysis of the electrolyzed
solution showed a total degradation of dimetridazole and the BOD5/COD ratio
increased from 0.13 to 0.24. An indirect electrochemical reduction in the
presence of titanocene dichloride ((C5H5)2TiCl2), which is used to reduce
selectively nitro compounds, was then investigated to favour the formation of
amino compounds over hydroxylamines and then to prevent the formation of azo and
azoxy dimers. UPLC-MS/MS analyses showed a higher selectivity towards the
formation of the amino compound for indirect electrolyses performed at pH 2. To
confirm the effectiveness of the electrochemical reduction, a biological
treatment involving activated sludge was then carried out after direct and
indirect electrolyses at different pH. The enhancement of the biodegradability
was clearly shown since mineralization yields of all electrolyzed solutions
increased significantly.
PMID- 28414945
TI - Evaluation of the chelating performance of biopolyelectrolyte green complexes
(NIBPEGCs) for wastewater treatment from the metal finishing industry.
AB - In this paper nonstoichiometric interbiopolyelectrolyte green complexes
(NIBPEGCs) were prepared using chitosan (Ch), alginate (AG) and poly(acrylic
acid)(PAA). They are proposed as innovative formulations (polyelectrolytes and
chelating agents) suitable for the elimination heavy metals contained in
wastewater. This application may represent an integral solution for industries
rejecting solid and aqueous metallic materials; however, it has not been
previously reported. NIBPEGCs physicochemical performance was evaluated based on
pH, particle size, surface charge, isoelectric point, dose, coagulation
flocculation kinetics and chemical affinity with seven metal ions. The
experimental results showed that NIBPEGCs composed by AG/Ch and PAA/Chitosan have
all the three complementary functions: chemical affinity, electrostatic
interaction and particle entrapment anticipating more simple operation units to
remove heavy metals. Complexes of AG/Ch (negative) were higher performance in
removing heavy metals, with a dose window (150-180mg/L), lower dose of 410mg/L
PAA/Ch (negative). Investigation of chelating performances of NIBPEGCs show that
the efficiency of metal removal is: Ca?Cr?Cu?Pb?Ni?Zn?Cd. Transmittance vs time
profiles, metals and zeta potential analysis showed that chelation capacity is
the crucial factor to ensure metallic species removal, followed by physical
entrapment of the metallic colloids. Integrating all presented results allow to
sustain the development of excellent metals removal formulations.
PMID- 28414946
TI - Green synthesis of hybrid graphene oxide/microcrystalline cellulose aerogels and
their use as superabsorbents.
AB - In this work, we developed a green synthesis method to prepare the hybrid
aerogels containing graphene oxide (GO) and microcrystalline cellulose (MCC)
using lithium bromide (LiBr) aqueous solution as the solvent, which insured the
complete dissolution of MCC. The interaction between GO and MCC was investigated
through different methods The results demonstrate that there is a strong
interaction between GO and MCC molecules, which promotes the exfoliation of GO in
the hybrid aerogels. The hybrid GO/MCC aerogels exhibit typical three dimensional
porous structure and the pore morphology can be well adjusted by changing the
content of GO. The adsorption ability of the hybrid aerogels was measured using
methylene blue (MB) as an adsorbate. The results show that the adsorption ability
of GO per unit mass is greatly enhanced compared with the pure GO aerogel,
especially at relatively low GO content the adsorption amount of GO per unit mass
is enhanced up to 2630mg/g. Further results demonstrate that the hybrid GO/MCC
aerogels still obey the pseudo-second-order adsorption model, which is similar to
that of the pure GO aerogel. The mechanism for the amplified adsorption ability
of GO in the hybrid GO/MCC aerogels is then analyzed.
PMID- 28414947
TI - Application of pyrolysis to recycling organics from waste tantalum capacitors.
AB - Tantalum capacitors (TCs) are widely used in electronic appliances. The rapid
replacement of electronic products results in generating large amounts of waste
TCs (WTCs). WTCs, rich in valuable tantalum, are considered as high quality
tantalum resources for recycling. However, environmental pollution will be caused
if the organics of WTCs were not properly disposed. Therefore, effectively
recycling the organics of WTCs is significant for recovering the valuable parts.
This study proposed an argon (Ar) pyrolysis process to recycle the organics from
WTCs. The organic decomposition kinetic was first analyzed by thermogravimetry.
The results showed that the organics were decomposed in two major steps and the
average activation energy was calculated to 234kJ/mol. Then, the suitable
pyrolysis parameters were determined as 550 degrees C, 30min and 100ml/min. The
organics were effectively decomposed and converted to oils (mainly contained
phenol homologs and benzene homologs) and gases (some hydrocarbon). These
pyrolysis products could be reutilized as energy sources. Moreover, based on the
products and bond energy theory, the pyrolysis mechanisms of the organics were
also discussed. Finally, a reasonable technological process for products
utilization was presented. This study contributes to the efficient recycling the
organics before valuable material recovery from WTCs.
PMID- 28414948
TI - Prognostic Factors for Niche Development in the Uterine Caesarean Section Scar.
AB - In a prospective study on 134 women after their first cesarean section prognostic
factors for developing an uterine niche (scar defect) measured with
sonohysterography were evaluated. With multivariable logistic regression anlaysis
the following prognostic factors were identified; enlarged cervical dilatation
and induction of labour. Contractions before labour reduced the risk for niche
development. The predictive value of the model made with this prognostic factors
was low. The development of a niche is a multifactorial proces and more studies
are needed.
PMID- 28414949
TI - EBV-encoded microRNAs profile evaluation in pediatric liver transplant
recipients.
AB - BACKGROUND: Epstein-Barr virus (EBV) infects 90% of the world population,
commonly causing self-limiting infectious mononucleosis or rarely inciting a
range of malignancies. EBV microRNAs (miRNAs) were discovered by sequencing
libraries of small RNAs generated from several EBV-positive cell lines. Little is
known about their roles, but their high stability and easy quantification make
these molecules potential biomarkers. OBJECTIVES: In this study a stem-loop MGB
real-time RT-PCR has been used to detect and quantify miR-BART2-5p, miR-BART15
and miR-BART22 EBV miRNAs levels. STUDY DESIGNS: The profiles of EBV miRNAs
levels were evaluated in 51 serum samples of 37 pediatric liver transplant
patients subdivided in 3 study groups: EBV seronegative, EBV seropositive and PCR
negative, EBV seropositive and PCR positive. RESULTS: miR-BART22 serum levels in
patients with positive EBV PCR were significantly higher than those in patients
with negative EBV PCR (p=0.0005). On the contrary, miR-BART2-5p and miR-BART15
did not exhibit significant difference in positive and negative EBV PCR patients
(p=0.5511 and p=0.3523, respectively). CONCLUSION: This study described a method
for quantitative detection of miR-BART 22, miR-BART2-5p and miR-BART15 EBV miRNAs
in liver transplanted patients, and suggests the use of miR-BART22 as a potential
biomarker for EBV reactivation.
PMID- 28414951
TI - Development of a two-photon fluorescent turn-on probe with far-red emission for
thiophenols and its bioimaging application in living tissues.
AB - Thiophenol is a highly toxic compound which is essential in the field of organic
synthesis and drug design. However, the accumulation of thiophenols in the
environment may cause serious health problems for human bodies ultimately.
Therefore, it is critical to develop efficient methods for visualization of
thiophenol species in biological samples. In this work, an innovative two-photon
fluorescent turn-on probe FR-TP with far-red emission for thiophenols based on FR
NH2 fluorophore and 2,4-dinitrophenylsulfonyl recognition site was reported. The
new probe can be used for thiophenol detection with large far-red fluorescence
enhancement (about 155-fold), rapid response (completed within 100s), excellent
sensitivity (DL 0.363MUM), high selectivity, and lower cellular auto-fluorescence
interference. Importantly, the probe FR-TP can be successfully employed to
visualize thiophenols not only in the living HeLa cells but also in living liver
tissues. In addition, through two-photon tissue imaging, the probe was used to
monitor and investigate biological thiophenol poisoning in the animal model of
thiophenol inhalation for the first time.
PMID- 28414950
TI - A nanobiosensor composed of Exfoliated Graphene Oxide and Gold Nano-Urchins, for
detection of GMO products.
AB - Genetically Modified Organisms, have been entered our food chain and detection of
these organisms in market products are still the main challenge for scientists.
Among several developed detection/quantification methods for detection of these
organisms, the electrochemical nanobiosensors are the most attended which are
combining the advantages of using nanomaterials, electrochemical methods and
biosensors. In this research, a novel and sensitive electrochemical nanobiosensor
for detection/quantification of these organisms have been developed using
nanomaterials; Exfoliated Graphene Oxide and Gold Nano-Urchins for modification
of the screen-printed carbon electrode, and also applying a specific DNA probe as
well as hematoxylin for electrochemical indicator. Application time period and
concentration of the components have been optimized and also several reliable
methods have been used to assess the correct assembling of the nanobiosensor e.g.
field emission scanning electron microscope, cyclic voltammetry and
electrochemical impedance spectroscopy. The results shown the linear range of the
sensor was 40.0-1100.0 femtomolar and the limit of detection calculated as 13.0
femtomolar. Besides, the biosensor had good selectivity towards the target DNA
over the non-specific sequences and also it was cost and time-effective and
possess ability to be used in real sample environment of extracted DNA of
Genetically Modified Organism products. Therefore, the superiority of the
aforementioned specification to the other previously published methods was proved
adequate.
PMID- 28414952
TI - Class 1 integrons as invasive species.
AB - Clinical class 1 integrons are a major contributor to the evolution and
dissemination of antibiotic resistance. The conserved motifs of these integrons
suggest that a single, recent ancestor gave rise to all current variants. They
have had a spectacular increase in distribution and abundance over the last 100
years, exhibiting many similarities to invasive species that prosper under human
impacts. They have spread into over 70 bacterial species of medical importance,
are commonly resident in the gut of humans and domesticated animals, and have
invaded every continent, including Antarctica. They have done so via linkage with
transposons, metal, disinfectant and antibiotic resistance genes. As a
consequence of their invasive nature they have now become significant pollutants
of natural environments.
PMID- 28414953
TI - Health shocks and their long-lasting impact on health behaviors: Evidence from
the 2009 H1N1 pandemic in Mexico.
AB - Worldwide, the leading causes of death could be avoided with health behaviors
that are low-cost but also difficult to adopt. We show that exogenous health
shocks could facilitate the adoption of these behaviors and provide long-lasting
effects on health outcomes. Specifically, we exploit the spatial and temporal
variation of the 2009 H1N1 influenza pandemic in Mexico and show that areas with
a higher incidence of H1N1 experienced larger reductions in diarrhea-related
cases among young children. These reductions continue even three years after the
shock ended. Health improvements and evidence of information seeking via Google
searches were consistent with changes in hand washing behaviors. Several
robustness checks validate our findings and mechanism.
PMID- 28414954
TI - Combination of microbial oxidation and biogenic schwertmannite immobilization: A
potential remediation for highly arsenic-contaminated soil.
AB - Here, a novel strategy that combines microbial oxidation by As(III)-oxidizing
bacterium and biogenic schwertmannite (Bio-SCH) immobilization was first proposed
and applied for treating the highly arsenic-contaminated soil. Brevibacterium sp.
YZ-1 isolated from a highly As-contaminated soil was used to oxidize As(III) in
contaminated soils. Under optimum culture condition for microbial oxidation,
92.3% of water-soluble As(III) and 84.4% of NaHCO3-extractable As(III) in soils
were removed. Bio-SCH synthesized through the oxidation of ferrous sulfate by
Acidithiobacillus ferrooxidans immobilize As(V) in the contaminated soil
effectively. Consequently, the combination of microbial oxidation and Bio-SCH
immobilization performed better in treating the highly As-contaminated soil with
immobilization efficiencies of 99.3% and 82.6% for water-soluble and NaHCO3
extractable total As, respectively. Thus, the combination can be considered as a
green remediation strategy for developing a novel and valuable solution for As
contaminated soils.
PMID- 28414955
TI - Influence of relaxation modes on membrane fouling in submerged membrane
bioreactor for domestic wastewater treatment.
AB - Relaxation and backwashing have become an integral part of membrane bioreactor
(MBR) operations for fouling control. This study was carried out on real
municipal wastewater to evaluate the influence of different operational
strategies on membrane fouling at equivalent water yield. Four relaxation modes
(MBR10+0, MBR10+1, MBR10+1.5 and MBR10+2) were tested to analyze membrane fouling
behavior. For the optimization of relaxation modes, fouling rate in terms of
trans-membrane pressure, hydraulic resistances and characteristics of fouling
fractions were analyzed. It has been observed that cake layer resistance was
minimum in MBR10+1.5 but pore blockage resistance was increased in all relaxation
modes. Moreover, high instantaneous flux contributed significantly to fouling
rate at the initial stage of MBR operations. Relaxation modes were also efficient
in removing irreversible fouling to some extent. Under all relaxation modes, COD
removal efficiency ranged from 92 to 96.5%. Ammonium and TP removal were on the
lower side due to the short solids and hydraulic retention time.
PMID- 28414956
TI - Geosmin as a source of the earthy-musty smell in fruits, vegetables and water:
Origins, impact on foods and water, and review of the removing techniques.
AB - The earthy-musty smell produced by Streptomyces sp. is assigned to geosmin and is
responsible for the major organoleptic defects found in drinking water, fruits
and vegetables such as grapes, mushrooms, carrots, and beet. Geosmin is also
found in juices and musts before fermentation and its presence has been
associated with partial presence of Botrytis cinerea. It has a variable detection
threshold depending on the matrix and the detection level ranges from 5 to 50
ng/L. On the sensory level, very few individuals are immune to geosmin and
although the intensity of the defect caused by this molecule decreases rapidly in
the nose, a bad taste is very persistent in the mouth. As the origin of geosmin
is fungal, conventional control techniques used for geosmin prevention are
limited to ventilation, improving the integrity of plants and use of storage
temperatures around 1 degrees C in a humidity-controlled environment. However,
it has been demonstrated that only the combination of different prophylactic and
preventive measures provide a relatively sufficient efficacy. Therefore,
prevention of factors favoring the formation of geosmin is still topical. Some
chemical treatments showed relatively good results against Botrytis cinerea.
However, there is a requirement that must be met, namely that only one chemical
per family per year must be used. Moreover, a multi-year alternation of chemical
families is a strong agronomic recommendation. Regarding Penicillium, no active
material is 100% approved and it negative effects plants such as beet and grapes.
Consequently, the importance of finding effective ways to fight against geosmin
formation is still relevant. From analytical point of view, measurement of
geosmin is mainly based on gas chromatography.
PMID- 28414957
TI - Emotion socialization and child conduct problems: A comprehensive review and meta
analysis.
AB - Decades of research have emphasized the role that coercive and ineffective
discipline plays in shaping child and adolescent conduct problems, yet an
emerging body of evidence has suggested that parents' emotion socialization
behaviors (ESBs) (e.g., reactions to emotions, discussion of emotions, and
emotion coaching) may also be implicated. This meta-analysis examined concurrent
and longitudinal associations between parental ESBs and conduct problems, and
tested for moderators of these associations. A systematic search identified 49
studies for which data on concurrent associations between ESBs and conduct
problems were available (n=6270), and 14 studies reporting on prospective
associations (n=1899). Parental ESBs were found to be significantly associated
with concurrent (r=-0.08) and prospective (r =-0.11) conduct problems, in the
order of small effect sizes. Key findings of moderator analyses were that ESBs
were more strongly associated with conduct problems at younger ages and when ESBs
were focused on the socialization of negative rather than positive emotions.
Findings support the integration of ESBs into family-based models of antisocial
behavior, and have the potential to inform the design of parent training
interventions for the prevention and treatment of child conduct problems.
PMID- 28414958
TI - The reappearance of hemiplegic cluster headaches: A case report and review of the
literature.
AB - Cluster headache (CH) is a rare and severe syndrome characterized by the
recurrence of unilateral pain attacks, of short duration (15-180min), and
associated with ipsilateral cranial autonomic symptoms. Although, not formally
included in the International Classification of Headache Disorders, hemiplegic
cluster headache (HCH) is an even more rare subtype of CH in which typical
attacks can be accompanied by visual, sensory, and/or aphasic migrainous auras
that have a variable propensity to evolve in reversible hemi-motor symptoms.
After its first description in 2002, only few cases of HCH have been reported and
many open questions about its prevalence and pathophysiology still need to be
addressed. We describe a case of a 41-year old male that fulfilled the ICHD
criteria for episodic CH who experienced atypical attacks characterized by
concomitant acute onset of sensory aura, aphasia and hemi-motor symptoms. We also
provide a concise review of the available literature and discuss the prevalence
and the possible pathogenesis of CH with hemiplegic features.
PMID- 28414959
TI - The visualization of the surgical field in tubular assisted spine surgery: Is
there a difference between HD-endoscopy and microscopy?
AB - OBJECTIVE: Expert spinal surgeons criticized endoscopic procedures for poor image
quality, in comparison to microscopic visualization. The recent introduction of
high definition (HD) digital cameras has shown good results in spinal endoscopy.
The aim of this study was to assess endoscopic HD image quality in comparison
with microscopic visualization. PATIENTS AND METHODS: All posterior lumbar and
cervical spinal surgeries of this study were performed with the EasyGO-system in
HD resolution. For each comparison, anatomical structures were predefined
intraoperatively. A junior resident was randomly required to enter the operating
theatre and to identify those structures either using HD-endoscopic or
microscopic visualization through the endoscopic working sheath. RESULTS:
Thirteen lumbar and three cervical procedures were performed. Thirty-four
comparisons with a total of 214 predefined anatomical structures were analyzed.
The number of predefined structures ranged from 5 to 9 per surgical field. Out of
214 predefined structures, 124 structures (65.8%) were correctly identified under
endoscopic view and 88 (41.1%) under microscopic view (p=0.001). Subjective
impression of visualization quality were rated 1.25 (very good) for endopscopic
images and 1.6 (very good to good) for microscopic view (p=0.02). CONCLUSIONS:
When using a working trocar and live images, endoscopic HD camera imaging
accounted for significantly more reliable identifications of anatomical
structures compared to the microscopic view. The subjective impression of video
quality is significantly better with HD-optics. The goal of further studies
should be to evalute if these findings results in improved surgical outcome.
PMID- 28414960
TI - Calibration of on-chip cell electroporation by a pseudo-volumetric uptake model.
AB - Most conventional methods for assessing uptake of exogenous molecules and
nanomaterials into cells use the projected two-dimensional (2D) area of uptake
intensity into individual cells. However, since most cells have a three
dimensional (3D) spherical shape, volumetric uptake cannot be quantified
accurately using 2D area analysis. Here, we present a method for calibrating the
electroporative uptake intensity of small molecules by using a novel predictable
spherical volume (PSV) model, which is more accurate and quantitative than
previous methods. As a proof-of-concept, we visualized the electroporative uptake
of propidium iodide (PI) into mammalian cells in a single rectangular
polydimethylsiloxane (PDMS) microfluidic channel, often used for direct
observation of on-chip cell electroporation. Our PSV method yielded more accurate
results than conventional methods and faithfully reflected volumetric changes in
uptake intensity, even those due to microflow. We believe that this approach can
be potentially beneficial for screening the electroporative uptake efficiency of
cell-membrane impermeable nanodrugs, such as functional nanoparticles
incorporated with a small drug capable of slowly diffusing inside cells.
PMID- 28414961
TI - Interaction between bacterial cell membranes and nano-TiO2 revealed by two
dimensional FTIR correlation spectroscopy using bacterial ghost as a model cell
envelope.
AB - The interaction between microorganisms and nanoparticles is a crucial step
towards understanding the subsequent biological effect. In this study, the
interaction between TiO2 nanoparticles and bacterial cell membrane was
investigated by Two-dimensional Correlation Fourier Transformation Infrared
spectroscopy (2D-FTIR-COS) using bacterial ghosts (BGs), which are non-living
bacterial cell envelopes devoid of cytoplasm. The synchronous map of 2D-FTIR-COS
results indicated that the functionalities in proteins of BGs preferentially
interacted with TiO2 nanoparticles; whereas the interaction of TiO2 nanoparticles
with characteristic functionality in polysaccharides (COH) and phospholipids (PO)
were very weak or insensitive. This conclusion was further corroborated by
settling of TiO2 nanoparticles in the presence of pure protein, polysaccharide
and phospholipid represented by bovine serum albumin (BSA), alginate and
phosphatidylethanolamine (PE). Additionally, the asynchronous map of 2D-FTIR-COS
indicated a sequential order of functionalities bonded to TiO2 nanoparticles with
the order of: COO- > aromatic CC stretching > NH, amide II > CO, ketone. These
findings contribute to deeper understanding of the interaction between TiO2
nanoparticles and bacterial cell membrane in aquatic systems.
PMID- 28414962
TI - Advanced anaerobic digestion of municipal sludge using a novel and energy
efficient radio frequency pretreatment system.
AB - Microwave (MW) sludge pretreatment systems are usually limited to a frequency of
2.45 GHz and the heating frequency is constrained by commercially available
hardware. Studies using MW heating at this frequency have reported negative net
energy balance (output energy as methane minus input electrical energy). This
necessitates further research into more efficient thermal pretreatment
technologies. In this research, a novel and highly efficient radio frequency (RF)
pretreatment system at a frequency of 13.56 MHz was designed, implemented, and
tested for the first time. The system was custom-designed based on the dielectric
characteristics of thickened waste activated sludge (TWAS) to achieve a very
efficient and uniform heating system. The effects of three factors including
pretreatment method (RF vs. MW), final temperature (60, 90 and 120 degrees C),
and stationary (holding) time (0, 1 and 2 h) on sludge solubilization and
performance of mesophilic batch anaerobic digestion were evaluated
simultaneously. Energy measurements were also made to compare the efficiency of
the custom-designed RF and conventional MW heating systems. The differences in
sludge disintegration (solubilization) using the RF and MW pretreatment systems
were negligible (P > 0.05). No statistically significant difference was also
observed between the two pretreatment systems in terms of mesophilic biogas
production rate and extent (P > 0.05). The energy efficiency of the RF
pretreatment system was measured between 67.3 and 95.5% for the temperature range
of 25-120 degrees C which was significantly higher than that of the MW system
efficiency which varied from 37 to 43%. Overall, the average input energy of the
RF system was less than half of the energy consumed during the operation of the
MW system to achieve a same target temperature. Considering the results of this
research, the RF heating at a frequency of 13.56 MHz is suggested as an effective
and energy-efficient technique for thermal hydrolysis of TWAS.
PMID- 28414963
TI - Three-dimensional excitation and emission matrix fluorescence (3DEEM) for quick
and pseudo-quantitative determination of protein- and humic-like substances in
full-scale membrane bioreactor (MBR).
AB - The goal of this study is to help filling the research gaps linked to the on-line
application of fluorescence spectroscopy in wastewater treatment and data
processing tools suitable for rapid correction and extraction of data contained
in three-dimensional fluorescence excitation-emission matrix (3DEEM) for real
time studies. 3DEEM was evaluated for direct quantification of Effluent Organic
Matter (EfOM) fractions in full-scale MBR bulk supernatant and permeate samples.
Principal Component Analysis (PCA) was used to investigate possible correlations
between conventional Lowry and Dubois methods, Liquid Chromatography coupled to
Organic Carbon and Organic Nitrogen Detection (LC-OCD-OND) and 3DEEM. 3DEEM data
were analyzed using the volume of fluorescence (Phi) parameter from the
Fluorescence Regional Integration (FRI) method. Two mathematical correlations
were established between LC-OCD-OND and 3DEEM data to quantify protein-like and
humic-like substances. These correlations were validated with supplementary data
from the initial full-scale MBR, and were checked with samples from other systems
(a second full-scale MBR, a full-scale conventional activated sludge (CAS) and a
laboratory-scale MBR). While humic-like correlation showed satisfactory
prediction for a second full-scale MBR and a CAS system, further studies are
required for protein-like estimation in other systems. This new approach offers
interesting perspectives for the on-line application of 3DEEM for EfOM
quantification (protein-like and humic-like substances), fouling prediction and
MBR process control.
PMID- 28414964
TI - Insights into the short-term effects of CeO2 nanoparticles on sludge dewatering
and related mechanism.
AB - As CeO2 nanoparticles (NPs) are used in many applications, the released particles
eventually enter wastewater treatment plants, influencing sludge dewatering and
increasing the disposal costs. We conducted tests to gain insight into the sludge
dewatering performance and the potential mechanism related to the distribution
and production of extracellular polymeric substances (EPS). In addition, we
conducted single-factor tests with six concentrations of CeO2 NPs in sequencing
batch reactors containing matured activated sludge. Overall, the specific
resistance to filtration (SRF) improved with an increase in the CeO2 NPs dosage.
The SRF significantly increased from 1.460 * 1012 to 1.632 * 1012 m/kg after the
addition of 5 mg/L CeO2 NPs (p < 0.05). The bound water content was enhanced from
2.43 to 2.75 kg/kg dry solid, indicating a deteriorated dewaterability. We found
that the increased EPS production, especially the dominant protein (r = 0.987, p
< 0.01), was correlated significantly with the SRF. This is ascribed to the
inhibited activity of leucyl aminopeptidase and the reduced adenosine 5'
triphosphate concentrations after exposure to CeO2 NPs. The fluorescence region
integration technique and protein secondary structures revealed the reasons for
the poor dewatering performance in the presence of CeO2 NPs. These are the
enhanced amount of soluble microbial by-product-like material and the low value
of the alpha-helix/(beta-sheet + random coil). These results could potentially
expand the knowledge on sludge dewatering in the presence of NPs.
PMID- 28414965
TI - Response to a mindful self-compassion intervention in teens: A within-person
association of mindfulness, self-compassion, and emotional well-being outcomes.
AB - As adolescence can be a stressful developmental stage, the purpose of this study
was to determine if a novel mindful self-compassion program would decrease
stress, depressive symptoms, and anxiety and increase resilience, gratitude, and
curiosity/exploration (positive risk-taking), and to ascertain if mindfulness and
self-compassion co-varied with these outcomes over time. Forty-seven adolescents
in the southeast U.S. enrolled in an 8-week mindful self-compassion course in
five cohorts. Measures were assessed at pre-intervention, post-intervention, and
6-week follow-up. Multilevel growth analyses revealed main effects of time on
perceived stress, resilience, curiosity/exploration and gratitude. Additionally,
both mindfulness and self-compassion co-varied with perceived stress and
depressive symptoms; mindfulness also co-varied with anxiety and self-compassion
co-varied with resilience and curiosity/exploration. Implications of these
findings are that this program has potential in decreasing stress and increasing
resilience and positive risk-taking. Future studies with a control group need to
be conducted to confirm these findings.
PMID- 28414966
TI - Modeling sleep and neuropsychiatric disorders in zebrafish.
AB - What are the molecular and cellular mechanisms that link neurological disorders
and sleep disturbances? The transparent zebrafish model could bridge this gap in
knowledge due to its unique genetic and imaging toolbox, and amenability to high
throughput screening. Sleep is well-characterized in zebrafish and key regulators
of the sleep/wake cycle are conserved, including melatonin and hypocretin/orexin
(Hcrt), whereas novel sleep regulating proteins are continually being identified,
such as Kcnh4a, Neuromedin U, and QRFP. Sleep deficiencies have been observed in
various zebrafish models for genetic neuropsychiatric disorders, ranging from
psychomotor retardation and autism to anxiety disorders. Understanding the link
between neuropsychiatric disorders and sleep phenotypes in zebrafish may
ultimately provide a platform for identifying therapeutic targets for clinical
trials in humans.
PMID- 28414967
TI - Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial
temporal lobe epilepsy.
AB - Patients with medically refractory epilepsy may benefit from resective epilepsy
surgery. However even the best centers experience surgical failures. It is
therefore important to find techniques that may aid in neurosurgical planning of
epileptic focus resection. Recordings of electrical brain activity with EEG
during seizures reveal abnormal cortical hypersynchronization. Between seizures
the EEG often shows interictal depolarizing phenomena such as spikes reflecting
an irritable focus of the brain. In the present study we investigated the effect
of intravenous remifentanil on the spike activity in the temporal neocortex and
hippocampus. We examined 65 patients with mesial temporal lobe epilepsy during
surgery, prior to resection. We used a 20-lead grid on the cortex and a 4-lead
strip in the lateral ventricle on the hippocampus. At least two 3-min periods of
ECoG were recorded - before and after remifentanil injection. In a number of
patients we examined the effect of repeated injections in order to estimate the
dose-response curve. We describe a significant effect of remifentanil on the
average spike activity with an increment from 16 spikes per minute at baseline to
36 spikes per minute after remifentanil injection (p<0.0001). The increase in
spike activity was typically seen after 40-50s. When mu-receptors were
antagonized with a preceding injection of naloxone, spike activity increased 25%
in response to remifentanil as opposed to 80% when remifentanil was preceded by
placebo. In only seven out of 59 patients did the injection of remifentanil
change the topographic location of the spike focus. Typically administration of
remifentanil led to a focus of increased spike count. Activity in other areas was
suppressed making the focus stand out from the background. Our observation that
remifentanil potentiates spike activity is in agreement with previous findings
from smaller studies. Furthermore, we were able to describe the pharmacodynamics
of the remifentanil effect on spike activity. Peri-operative provocation with
remifentanil may play a future role in guiding neurosurgical intervention during
epilepsy resection surgery.
PMID- 28414968
TI - Investigating the correlation between short-term effectiveness of VNS Therapy in
reducing the severity of seizures and long-term responsiveness.
AB - VNS (Vagus Nerve Stimulation) Therapy(r) is an adjunctive therapy for patients
with medically refractory epilepsy. The primary metric used to assess response to
any treatment for epilepsy is seizure frequency reduction as measured using
seizure diaries. In addition to seizure frequency, reduction in seizure severity
is clinically meaningful to patients and can be measured objectively. Analysis of
electro-encephalographic (EEG) signals has revealed that seizures are accompanied
by spatial synchronization of EEG electrodes that may persist for several minutes
after the seizure. A quantitative feature was obtained from EEG data around ictal
events collected during a 3-5day epilepsy monitoring unit (EMU) visit prior to
VNS implantation and following one month after VNS implant. This feature was
obtained from 15 patients who underwent implantation of the closed-loop
AspireSR(r) VNS Therapy System. We used this feature to first evaluate if
automated delivery of VNS at the time of seizure onset reduces the severity of
seizures in patients by reducing EEG spatial synchronization. We then explored
the correlation between the effectiveness of VNS in reducing the severity of
seizures and long-term (12 month follow-up) responsiveness using clinical metrics
of seizure frequency reduction. Results of application of this methodology to 103
pre-VNS and 102 post-VNS seizures revealed that automatic delivery of VNS Therapy
reduces ictal spatial synchronization (EEG-based quantitative feature) in
patients who responded (>=50% reduction in seizure frequency) to VNS Therapy.
This feature may be used as potential biomarker for predicting long-term response
to VNS Therapy.
PMID- 28414969
TI - Cytokines in the management of rotavirus infection: A systematic review of in
vivo studies.
AB - OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus
vaccines are effective against severe rotavirus gastroenteritis, but have lower
efficacy in low income countries in Africa. Anti-rotavirus treatment is not
available. This study reviews the literature of animal studies evaluating whether
cytokine mediated pathways of immune activation could improve rotavirus therapy.
METHODS: We performed a systematic review of articles in English published from
2010 to 2016 reporting agents with in vivo antirotavirus activity for the
management of rotavirus infection. The search was carried in PubMed, EMBASE,
Scopus and Web of Science. Animal experiments where cytokines were investigated
to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869
publications were identified. Of these, 19 pertained the objectives of the
review, and 11 articles described the effect of probiotics/commensals on
rotavirus infection and immune responses in animals. Eight further in vivo
studies evaluated the immunomodulating effects of herbs, secondary metabolites
and food-derived products on cytokine responses of rotavirus-infected animals.
Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon
gamma (IFN-gamma), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10)
cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus
infection through suppression of inflammation by viral inhibition. CONCLUSION:
Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding
and/or replication in animal models. Th1/Th2 cytokine responses have optimal
immunomodulating effects to reduce rotavirus diarrhoea and enhance immune
responses in experimental rotavirus infection.
PMID- 28414970
TI - Understanding deceptive intentions behind pointing gestures in 12-15-month-old
infants.
AB - We examined the comprehension of deceptive intentions revealed in searching task
in infancy, on the theoretical basis of natural pedagogy and epistemic trust. The
main findings showed that 12-15-month-old infants are able to discriminate the
reliable and the deceptive actions of adults, but they do not generalize their
previous experience in connection with a novel person, who is treated as a new
reliable source of information.
PMID- 28414971
TI - Influence of sulfur fumigation on the chemical profiles of Atractylodes
macrocephala Koidz. evaluated by UFLC-QTOF-MS combined with multivariate
statistical analysis.
AB - In the present study, the chemical compositions of Atractylodes macrocephala
Koidz. (AMK) were analyzed systematically and influence of sulfur fumigation on
the chemical profiles was evaluated by ultrafast flow liquid chromatography
coupled with quadrupole-time-of-flight mass spectrometry (UFLC-QTOF-MS) combined
with multivariate statistical analysis. 52 components were detected from non
fumigated AMK (NF-AMK) and 28 components were newly produced after sulfur
fumigation, out of which 59 major peaks were identified. The concentrations of 20
compounds significantly decreased and 37 compounds obviously increased. The
potential structural transformation mechanism of terpenoids was explored to
illustrate the correlation of the components contents before and after sulfur
fumigation. Eight sulfur-containing/dehydrated-integrated atractylenolides that
evolved from the NF-AMK were screened out as potential characteristic chemical
markers to examine the post-harvest handling procedures of commercial AMK with
excessive sulfur fumigation and maintain consistent quality.
PMID- 28414972
TI - An LC-MS/MS method for quantification of AC0010, a novel mutant-selective
epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human
plasma and the application to a pharmacokinetic study.
AB - AC0010 is an irreversible, mutant-selective EGFR inhibitor that effectively
inhibits EGFR active and T790M resistance mutations in non-small cell lung cancer
(NSCLC). A sensitive ultra-performance liquid chromatography - tandem mass
spectrometry (UPLC-MS/MS) method was developed and fully validated for
determining AC0010 and its metabolites in human plasma. The samples were purified
by solid-phase extraction (SPE) columns and separated on a BEH C18 column.
Electrospray ionization (ESI) in positive ion mode and multiple reaction
monitoring (MRM) were used to monitor the ion transitions of AC0010 (m/z 488
>257) and its metabolites M1 (m/z 474->403), M2 (m/z 504->487), M4 (m/z 434
>377), M7 (m/z 490->405), MII-1 (m/z 651->434) and MII-2 (m/z 609->434). The
results revealed that the method had excellent selectivity and linearity. Intra
day and inter-day precisions (in terms of relative standard deviation, RSD) were
lower than 14.4% and the accuracies (in terms of relative error, RE) were within
the range of +/-10.3% for all the analytes. The lower limit of quantification
(LLOQ), stability, matrix effect and extraction recovery were also validated and
satisfied the criteria of validation. Finally, the method was successfully
applied to a pharmacokinetic study of NSCLC patients after a single oral dose of
350mg of AC0010.
PMID- 28414973
TI - Regulation of antibiotic-resistance by non-coding RNAs in bacteria.
AB - Antibiotic resistance genes are commonly regulated by sophisticated mechanisms
that activate gene expression in response to antibiotic exposure. Growing
evidence suggest that cis-acting non-coding RNAs play a major role in regulating
the expression of many resistance genes, specifically those which counteract the
effects of translation-inhibiting antibiotics. These ncRNAs reside in the 5'UTR
of the regulated gene, and sense the presence of the antibiotics by recruiting
translating ribosomes onto short upstream open reading frames (uORFs) embedded in
the ncRNA. In the presence of translation-inhibiting antibiotics ribosomes arrest
over the uORF, altering the RNA structure of the regulator and switching the
expression of the resistance gene to 'ON'. The specificity of these
riboregulators is tuned to sense-specific classes of antibiotics based on the
length and composition of the respective uORF. Here we review recent work
describing new types of antibiotic-sensing RNA-based regulators and elucidating
the molecular mechanisms by which they function to control antibiotic resistance
in bacteria.
PMID- 28414974
TI - Bilirubin nanoparticle preconditioning protects against hepatic ischemia
reperfusion injury.
AB - Hepatic ischemia-reperfusion injury (IRI) remains a major concern in liver
transplantation and resection, despite continuing efforts to prevent it.
Accumulating evidence suggests that bilirubin possesses antioxidant, anti
inflammatory and anti-apoptotic properties. However, despite obvious potential
health benefits of bilirubin, its clinical applications are limited by its poor
solubility. We recently developed bilirubin nanoparticles (BRNPs) consisting of
polyethylene glycol (PEG)-conjugated bilirubin. Here, we sought to investigate
whether BRNPs protect against IRI in the liver by preventing oxidative stress.
BRNPs exerted potent antioxidant and anti-apoptotic activity in primary
hepatocytes exposed to hydrogen peroxide, a precursor of reactive oxygen species
(ROS). In a model of hepatic IRI in mice, BRNP preconditioning exerted profound
protective effects against hepatocellular injury by reducing oxidative stress,
pro-inflammatory cytokine production, and recruitment of neutrophils. They also
preferentially accumulated in IRI-induced inflammatory lesions. Collectively, our
findings indicate that BRNP preconditioning provides a simple and safe approach
that can be easily monitored in the blood like endogenous bilirubin, and could be
a promising strategy to protect against IRI in a clinical setting.
PMID- 28414975
TI - Fullerene-doped polyaniline as new redox nanoprobe and catalyst in
electrochemical aptasensor for ultrasensitive detection of Mycobacterium
tuberculosis MPT64 antigen in human serum.
AB - Tuberculosis caused by Mycobacterium tuberculosis (MTB) is still a major threat
to global public health. However, the existing methods for MTB detection are
usually complicated and time consuming with unsatisfactory sensitivity and
specificity. In this work, a relatively simple and ultrasensitive electrochemical
aptasensor based on novel signal generation and amplification was constructed for
the determination of MTB antigen MPT64. The coil-like fullerene (C60)-doped
polyaniline (C60-PAn) nanohybrids with large surface area, abundant active groups
and excellent electric performance were synthesized and used both as new redox
nanoprobe and catalyst for the generation and amplification of electrochemical
signal for the first time. Then gold nanoparticles decorated C60-PAn
nanocomposites (GNPs-C60-PAn) were labeled with signal aptamer to form the tracer
label. After the sandwich reaction of target MPT64 antigen between capture
aptamer and the tracer label, a distinguishing detection signal of C60-PAn would
be observed. Moreover, the detection signal could be enormously enhanced towards
the efficient electrocatalytic oxidation of ascorbic acid based on C60-PAn,
resulting in further improvement of the sensitivity. With the excellent redox and
electrocatalytic activity of C60-PAn, a wide detection linear range from 0.02 to
1000 pg/mL was obtained with a detection limit of 20 fg/mL for MPT64. The
proposed aptasensor showed high selectivity to target antigen compared with
possible interfering substances. More importantly, it also exhibited excellent
specificity and sensitivity for MPT64 detection in serum samples of tuberculosis
patients, which provided a rapid and efficient detection method for MTB
infection.
PMID- 28414976
TI - Glucose-sensitive self-healing hydrogel as sacrificial materials to fabricate
vascularized constructs.
AB - A major challenge in tissue engineering is the lack of proper vascularization.
Although various approaches have been used to build vascular network in a tissue
engineering construct, there remain some drawbacks. Herein, a glucose-sensitive
self-healing hydrogel are employed as sacrificial materials to fabricate branched
tubular channels within a construct. The hydrogel composes of mainly reversibly
crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax as the
glucose-sensitive motif. The hydrogel is injectable and mechanically strong after
injection. Moreover, it can be rapidly removed by immersion in the cell culture
medium. To show the feasibility in building a vascularized tissue construct, the
designed branching vascular patterns of the glucose-sensitive hydrogel are
extruded and embedded in a non glucose-sensitive hydrogel containing neural stem
cells. Vascular endothelial cells seeded in the lumen of the channels by
perfusion can line the channel wall and migrate into the non-sacrificial hydrogel
after 3 days. In long-term (~14 days), the endothelial cells form capillary-like
structure (vascular network) while neural stem cells form neurosphere-like
structure (neural development) in the construct, revealing the morphology of "a
vascularized neural tissue". The novel sacrificial materials can create
complicated but easily removable structure for building a vascularized tissue
construct particularly a neurovascular unit.
PMID- 28414977
TI - Design of the magnetic homonuclear bonds boron nitride nanosheets using DFT
methods.
AB - Design and characterization of the structural, electronic, and magnetic
properties of armchair boron-nitride, BN (B27N27H18), nanosheets were performed
by means of density functional theory all-electron calculations. The HSEh1PBE-GGA
method together with 6-31G(d) basis sets were used. Non-stoichiometric B30N24H18
and B24N30H18 compositions: rich in boron or nitrogen atoms, forming homonuclear
B or N bonds, respectively, were chosen. The obtained results reveal that these
BN nanosheets reach structural stability in the anionic form, where semiconductor
and magnetic behaviors are promoted. Effectively, the HOMO-LUMO gap is of 2.03
and 2.39eV, respectively and the magnetic moments are of 1.0 magneton bohrs,
coming from the boron atoms in both systems. The rich in boron nanosheets present
high-polarity, either in the gas phase or embedded in aqueous mediums like water,
as well as low chemical reactivity, signifying potential applicability in the
transportation of pharmaceutical species in biological mediums. These systems are
also promising for the design of electronic devices, because they possess low
work functions, mainly arising from the homonuclear boron or nitrogen bond
formation.
PMID- 28414978
TI - Investigation on the relationship between solubility of artemisinin and
polyvinylpyrroli done addition by using DAOSD approach.
AB - In this work, we investigated the influence of polyvinylpyrrolidone (PVP) on the
solubility of artemisinin in aqueous solution by using quantitative 1H NMR.
Experimental results demonstrate that about 4 times of incremental increase
occurs on the solubility of artemisinin upon introducing PVP. In addition, dipole
dipole interaction between the ester group of artemisinin and the amide group of
N-methylpyrrolidone (NMP), a model compound of PVP, is characterized by two
dimensional (2D) correlation FTIR spectroscopy with the DAOSD (Double
Asynchronous Orthogonal Sample Design) approach developed in our previous work.
The observation of cross peaks in a pair of 2D asynchronous spectra suggests that
dipole-dipole interaction indeed occurs between the ester group of artemisinin
and amide group of NMP. Moreover, the pattern of cross peaks indicates that the
carbonyl band of artemisinin undergoes blue-shift while the bandwidth and
absorptivity increases via interaction with NMP, and the amide band of NMP
undergoes blue-shift while the absorptivity increases via interaction with
artemisinin. Dipole-dipole interaction, as one of the strongest intermolecular
interaction between artemisinin and excipient, may play an important role in the
enhancement of the solubility of artemisinin in aqueous solution.
PMID- 28414979
TI - Role of EGF on in situ culture of equine preantral follicles and metabolomics
profile.
AB - The effects of epidermal growth factor (EGF) concentrations (0, 10, 50, and
100ng/ml) on in vitro culture (IVC) of equine preantral follicles were evaluated
using histology, estradiol and reactive oxygen species (ROS) production and
metabolomics. After IVC, the percentage of normal follicles was lower (P<0.05)
for all treatments when compared to non-cultured control. EGF 50ng/ml treatment
had more (P<0.05) normal follicles at Day 7 of culture when compared with EGF 0
and 100ng/ml. EGF 50ng/ml had more (P<0.05) developing follicles than the 0ng/ml
and 10ng/ml EGF treatments. Follicular and oocyte diameters were greater (P<0.05)
with EGF 50ng/ml than the other cultured treatments, but similar (P>0.05) to the
non-cultured control. From Day 1 to Day 7 estradiol production increased (P<0.05)
in all EGF treatments. EGF 50ng/ml was the only treatment that maintained ROS
production through IVC. Metabolomics profiles of the spent media indicated that
eleven ions from variable influence in the projection (VIP) scores were higher
represented in the EGF 50ng/ml treatment. In conclusion, EGF 50ng/ml treatment
maintained follicle survival and ROS production, and promoted activation of
cultured equine preantral follicles enclosed in ovarian tissue.
PMID- 28414980
TI - Fluorescence and circular dichroism studies on the accessibility of tryptophan
residues and unfolding of a jacalin-related alpha-d-galactose-specific lectin
from mulberry (Morus indica).
AB - MLGL (Mulberry Latex Galactose-specific Lectin) is an alpha-d-galactose binding
lectin isolated from the latex of mulberry (Morus indica) tree and contains two
tryptophan residues in each of its subunits. The fluorescence emission maximum of
native MLGL seen at 326nm shifts to 350nm upon incubation with 6M guanidinium
thiocyanate (Gdn.SCN), suggesting that the tryptophans are located inside the
hydrophobic core of the protein and become fully exposed upon denaturation.
Fluorescence quenching studies revealed that the neutral acrylamide exhibits the
highest quenching, with ~33% of total fluorescence in the native protein being
quenched at a quencher concentration of 0.5M, whereas iodide (~24%) and cesium
(~4%) ions showed significantly lower quenching. With the denatured protein,
acrylamide quenching involves both dynamic and static processes as evident from
an upward curving Stern-Volmer plot. Time-resolved fluorescence studies showed
two lifetime components of 3.7ns and 1.3ns for the native protein, while three
lifetime components were observed for the denatured protein. MLGL showed high
resistance to urea (up to 8M) and guanidine hydrochloride (up to 6M), whereas
treatment with 6M Gdn.SCN completely denatured the protein, via a broad sigmoidal
transition with a transition midpoint at ~3.75M. Circular dichroism studies and
hemagglutination assays showed that the secondary and tertiary structures as well
as lectin activity of MLGL were unaffected up to 70 degrees C. Additionally, pH
dependent studies showed that the secondary structure of MLGL is unaltered in the
pH range 6.2 to 8.5, but a decrease in lectin activity is observed (~50%) at
pH6.2.
PMID- 28414981
TI - Claims in vapour device (e-cigarette) regulation: A Narrative Policy Framework
analysis.
AB - BACKGROUND: The electronic cigarette or e-cigarette (vapour device) is a consumer
product undergoing rapid growth, and governments have been adopting regulations
on the sale of the devices and their nicotine liquids. Competing claims about
vapour devices have ignited a contentious debate in the public health community.
What claims have been taken up in the state arena, and how have they possibly
influenced regulatory outcomes? METHODS: This study utilized Narrative Policy
Framework to analyze the claims made about vapour devices in legislation
recommendation reports from Queensland Australia, Canada, and the European Union,
and the 2016 deeming rule legislation from the United States, and examined the
claims and the regulatory outcomes in these jurisdictions. RESULTS: The vast
majority of claims in the policy documents represented vapour devices as a
threat: an unsafe product harming the health of vapour device users, a gateway
product promoting youth tobacco uptake, and a quasi-tobacco product impeding
tobacco control. The opportunity for vapour devices to promote cessation or
reduce exposure to toxins was very rarely presented, and these positive claims
were not discussed at all in two of the four documents studied. CONCLUSION: The
dominant claims of vapour devices as a public health threat have supported
regulations that have limited their potential as a harm reduction strategy.
Future policy debates should evaluate the opportunities for vapour devices to
decrease the health and social burdens of the tobacco epidemic.
PMID- 28414982
TI - Relation of positive fluid balance to the severity of renal impairment and
recovery among ST elevation myocardial infarction complicated by cardiogenic
shock.
AB - PURPOSE: We analyzed the relationship between a positive fluid balance and its
persistence over time on acute kidney injury (AKI) development, severity and
resolution among ST elevation myocardial infarction (STEMI) patients complicated
by cardiogenic shock. METHODS: We retrospectively studied the cumulative fluid
balance intake and output at 96h following hospital admission in 84 consecutive
adult patients with STEMI complicated by cardiogenic shock. The cohort was
stratified into two groups, based on the presence or absence of positive fluid
balance on day 4. Patients' records were assessed for the development of AKI, AKI
severity and recovery. RESULTS: Patients having positive fluid balance were more
likely to develop a more severe AKI stage (52% vs. 13%; p<0.001), were less
likely to have recovery of their renal function (29% vs. 75%, p=0.001), and
demonstrated positive correlation between the amount of fluid accumulated and the
rise in serum creatinine (R=0.42, p=0.004). For every 1l increase in positive
fluid balance, the adjusted possibility for recovery of renal function decreased
by 21% (OR=0.796, 95% CI 0.67-0.93; p=0.006). CONCLUSIONS: A positive fluid
balance was strongly associated with higher stage AKI and lower rate of AKI
recovery in STEMI complicated by cardiogenic shock.
PMID- 28414983
TI - A randomised controlled trial in comparing maternal and neonatal outcomes between
hands-and-knees delivery position and supine position in China.
AB - BACKGROUND: the supine position is the most frequently offered for birth delivery
in China and many other countries, but the hands-and-knees position is now
gaining prominence with doctors in China. This study aims to examine the
differences in maternal and neonatal outcomes among low-risk women who gave birth
either in the hands-and-knees position or the supine position. METHODS: a
randomised controlled trial was conducted in 11 hospitals in China from May to
December in 2012. In total, 1400 women were recruited and randomly allocated to
either the experimental group (n=700, 446 completed the protocol) who delivered
in hands-and-knees position and the control group (n=700, 440 completed the
protocol) who delivered in supine position. Women who could not maintain the
randomised position during the second stage of labour were allowed to withdraw
from the study. The primary maternal outcome measured was rate of episiotomy.
Secondary outcomes included degree of perineum laceration, rate of emergency
caesarean section, rate of shoulder dystocia, and duration of labour, postpartum
bleeding, neonatal Apgar score, and the rate of neonatal asphyxia. Because
outcome data were only collected for women who gave birth in the randomised
position, per-protocol analyses were used to compare groups. The primary outcome,
episiotomy, was also compared between groups using logistic regression adjusting
for maternal age,gestational age at birth, whether the woman was primiparous, the
process of second stage of labour and birthweight. FINDINGS: as compared with the
control group, the experimental group had lower rates of episiotomy and second
degree perineum laceration (including episiotomy), and higher rates of intact
perineum and first-degree perineum laceration, with a longer duration of second
stage of labour. No significant differences were found in the amount of
postpartum bleeding, shoulder dystocia, neonatal asphyxia and neonatal Apgar
scores at 1minute and 5minutes. Adjusted for maternal age, gestational age,
parity, duration of second stage of labour and birth weight, the hands-and-knees
position reduced the need for episiotomy (OR=0.024, p<0.001). CONCLUSIONS: this
study provided evidence that women who could maintain the hands-and-knees
position during the second stage of labour had lower rates of episiotomy and
second-degree perineum laceration (including episiotomy). Both midwives and
obstetricians are suggested to learn the skills to assist women with delivery in
this position.
PMID- 28414984
TI - A fully synthetic lung model for wound-ballistic experiments-First results.
AB - PURPOSE: Today, synthetic models have all but replaced animal and corpse models
in examining damage to soft-tissues and skeletal structures by ballistic trauma.
As, however, non-solid organs such as the lungs, have not been able to be
replaced by a fully synthetic model we attempted to create such a model. MATERIAL
AND METHODS: 20% ordnance gelatine was frothed with a household mixer and cooled
to stable foam. Several of these foam blocks were then stuck together with liquid
gelatine and placed between 10% gelatine blocks. As controls, we embedded pig
lungs in gelatine and compared the wound channels seen in computed tomography
created upon shooting with 9mm Luger. RESULTS: The fully synthetic models
displayed radiological and physical densities comparable to real lungs. The wound
profile characteristics of the fully synthetic lung models were very similar to
the semisynthetic swine-gelatine models regarding the permanent wound cavity.
Furthermore, in both semi- and fully synthetic models we detected a ring
surrounding the permanent wound channel, most likely representing the remnants of
the temporary wound cavity. CONCLUSION: Our results indicate that this fully
synthetic lung model is a viable substitute for ballistic experiments on lungs.
We believe that further research on the temporary wound channel in lungs is
possible with this model in order to provide more insight into the effect of
ballistic trauma to the lungs not seen otherwise.
PMID- 28414985
TI - Sharp and blunt force trauma concealment by thermal alteration in homicides: An
in-vitro experiment for methodology and protocol development in forensic
anthropological analysis of burnt bones.
AB - Burning of human remains is one method used by perpetrators to conceal fatal
trauma and expert opinions regarding the degree of skeletal evidence concealment
are often disparate. This experiment aimed to reduce this incongruence in
forensic anthropological interpretation of burned human remains and implicitly
contribute to the development of research methodologies sufficiently robust to
withstand forensic scrutiny in the courtroom. We have tested the influence of
thermal alteration on pre-existing sharp and blunt trauma on twenty juvenile
sheep radii in the laboratory using an automated impact testing system and an
electric furnace. The testing conditions simulated a worst-case scenario where
remains with pre-existing sharp or blunt trauma were exposed to burning with an
intentional vehicular fire scenario in mind. All impact parameters as well as the
burning conditions were based on those most commonly encountered in forensic
cases and maintained constant throughout the experiment. The results have shown
that signatures associated with sharp and blunt force trauma were not masked by
heat exposure and highlights the potential for future standardization of fracture
analysis in burned bone. Our results further emphasize the recommendation given
by other experts on handling, processing and recording burned remains at the
crime scene and mortuary.
PMID- 28414986
TI - Modelling dental implant extraction by pullout and torque procedures.
AB - Dental implants extraction, achieved either by applying torque or pullout force,
is used to estimate the bone-implant interfacial strength. A detailed description
of the mechanical and physical aspects of the extraction process in the
literature is still missing. This paper presents 3D nonlinear dynamic finite
element simulations of a commercial implant extraction process from the mandible
bone. Emphasis is put on the typical load-displacement and torque-angle
relationships for various types of cortical and trabecular bone strengths. The
simulations also study of the influence of the osseointegration level on those
relationships. This is done by simulating implant extraction right after
insertion when interfacial frictional contact exists between the implant and
bone, and long after insertion, assuming that the implant is fully bonded to the
bone. The model does not include a separate representation and model of the
interfacial layer for which available data is limited. The obtained relationships
show that the higher the strength of the trabecular bone the higher the peak
extraction force, while for application of torque, it is the cortical bone which
might dictate the peak torque value. Information on the relative strength
contrast of the cortical and trabecular components, as well as the progressive
nature of the damage evolution, can be revealed from the obtained relations. It
is shown that full osseointegration might multiply the peak and average load
values by a factor 3-12 although the calculated work of extraction varies only by
a factor of 1.5. From a quantitative point of view, it is suggested that, as an
alternative to reporting peak load or torque values, an average value derived
from the extraction work be used to better characterize the bone-implant
interfacial strength.
PMID- 28414987
TI - Effects of different radiation doses on the microhardness, superficial
morphology, and mineral components of human enamel.
AB - OBJECTIVE: To evaluate the effects of three different radiotherapy doses (20, 40,
and 70Gy) on the microhardness, superficial morphology, and mineral content
(based on Ca and P values) of three different depths of human enamel (cervical,
middle, and occlusal). DESIGN: Thirty-four third molars were cut, separated, and
prepared. Microhardness samples (n=30) were embedded in acrylic resin and then
polished, and depths were delimited. Microhardness tests were performed on
cervical, middle, and occlusal enamel pre- and post-radiotherapy with a load of
50g for 30s. For the scanning electron microscopy (SEM) analysis (n=4) and energy
dispersive X-ray spectroscopy (EDS) (n=12), samples were fixed in a 3%
glutaraldehyde solution, washed in 0.1M cacodylate solution, and dehydrated in
crescent concentrations of ethanol. Microhardness data were tested for
significant differences using a two-way analysis of variance (ANOVA) and Tukey's
test (p<0.05), while SEM and EDS were evaluated qualitatively. RESULTS: The
results showed a decrease in microhardness values only in the cervical enamel,
regardless of the radiation dose used; no morphological or mineral change was
observed. CONCLUSION: Radiotherapy can affect the microhardness values of only
cervical enamel without compromising the morphological or mineral (Ca and P)
content at any depth.
PMID- 28414988
TI - Response of mandibular condyles of juvenile and adult rats to abnormal occlusion
and subsequent exemption.
AB - OBJECTIVE: The adaptation capacities of the mandibular condyle in response to
mechanical stimuli might be different between juveniles and adults, but has not
been compared. This study aimed to investigate whether abnormal molar occlusion
and subsequent molar extraction could lead to different remodeling responses in
the mandibular condyles of juvenile and adult rats. METHODS: Abnormal molar
occlusion (AMO) was established in the 5- and 16-wk old rats by moving their
maxillary left and mandibular right third molars distally. AMO was removed in the
molar extraction group at 4 weeks but remained in the AMO group. All rats were
sacrificed at 8 weeks. Micro-computed tomography, histomorphology,
immunohistochemistry and real-time PCR were adopted to evaluate the remodeling of
condylar subchondral bone. RESULTS: Condylar subchondral bone loss and increased
osteoclastic activities were observed in both juvenile and adult AMO groups,
while increased osteoblastic activities were only seen in the juvenile AMO group.
Decreased bone mineral density, bone volume fraction and trabecular thickness,
but increased trabecular separation, number and surface of osteoclasts and mRNA
levels of TRAP, cathepsin-K, RANKL in the juvenile AMO group were all reversed
after molar extraction (all P<0.05). However, these parameters showed no
difference between adult AMO and extraction groups (all P>0.05). CONCLUSIONS:
Abnormal molar occlusion led to degenerative remodeling in the mandibular
condyles of both juvenile and adult rats, while exemption of abnormal occlusion
caused significant rescue of the degenerative changes only in the juvenile rats.
PMID- 28414990
TI - Medical outcomes associated with prescription opioid abuse via oral and non-oral
routes of administration.
AB - BACKGROUND: Prescription opioid abuse and misuse is a serious and growing public
health issue. While the most common form of abuse is swallowing intact
tablets/capsules, some abusers manipulate, or tamper with, these medications by
altering the dosage form to allow for non-oral routes of administration (e.g.,
injection, inhalation) in order to achieve more rapid or enhanced psychoactive
effects. Because administration of opioids via non-oral routes results in greater
systemic availability and more rapid central nervous system penetration, we
hypothesized that death and major medical outcomes occur more frequently with non
oral routes compared to oral route alone. METHODS: This retrospective cohort
study analyzed data from the Researched Abuse, Diversion and Addiction-Related
Surveillance (RADARS) System Poison Center Program to investigate relative risk
of prescription opioid abuse via oral and non-oral routes. RESULTS: While the
oral route was the most commonly reported route of abuse (64.0%), non-oral routes
were reported in 14.6% exposures and unknown routes in 21.4% exposures. The
relative risk of an exposure resulting in death or major effect was 2.43 (95% CI
1.97, 2.99) if non-oral routes were reported compared to exposures involving oral
route only. CONCLUSION: Analysis of acute health events recorded by poison
centers indicates that death or major effects are twice as likely to occur with
intentional abuse of prescription opioids via non-oral routes of administration
than ingestion alone. Effective interventions to prevent abuse via non-oral
routes of solid dosage forms of prescription opioids, such as abuse-deterrent
formulations could have a significant public health impact.
PMID- 28414991
TI - Modeling the detection efficiency of an HP-Ge detector for use in boron neutron
capture therapy.
AB - The multi-foil method is commonly used to determine upon an energy spectrum of
neutrons in boron neutron capture therapy. The method requires to measure the
radioactivation of the foils. This study develops a simple modeling procedure of
a high-purity Ge detector, which is used to measure the radioactivation, in order
to calculate the detection efficiency with GEANT4. By changing four parameters
from their manufacturing specifications of the detector, the simulated detection
efficiency is able to reproduce the actual detection efficiency.
PMID- 28414989
TI - Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression
and tricyclic antidepressants.
AB - INTRODUCTION: Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol
use disorder (AUD) and depression is suggested, very little information on a
direct interaction between alcohol and these receptors is available. METHODS: In
this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal
model of depression, were exposed to alcohol vapor 3h daily for 10days (blood
alcohol concentration ~150mg%) followed by daily injection of 10mg/kg of
imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or
nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals
were tested for open field locomotor activity (OFLA) and forced swim test (FST)
and were sacrificed 2h later for measurement of alpha-2 ARs densities in the
frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand.
RESULTS: Chronic alcohol treatment increased the immobility in the FST, without
affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive
like behavior in Wistar rats and an exacerbation of this behavior in WKY rats.
Alcohol treatment also resulted in an increase in cortical but not hippocampal
alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of
alcohol were completely blocked by IMP and NOMI and the neurochemical effects
(increases in alpha-2 ARs) were significantly attenuated by both drugs in both
strains. CONCLUSIONS: The results suggest a role for cortical alpha-2 ARs in
alcohol withdrawal-induced depression and that selective subtype antagonists of
these receptors may be of adjunct therapeutic potential in AUD-depression co
morbidity.
PMID- 28414993
TI - Chikungunya virus infections: time to act, time to treat.
AB - Chikungunya virus (CHIKV) is a re-emerging alphavirus that caused massive
outbreaks of Chikungunya fever in several countries and regions in Africa, Asia
and more recently in Central and South America. An acute CHIKV infection is
usually associated with fever and arthritis and it is rarely fatal. However, 15
60% of patients suffer from chronic polyarthralgia for weeks, months or even for
several years after the acute infection. There are currently no vaccines or
antivirals available for the prevention or treatment of CHIKV infections. The
development of potent and safe antivirals for prophylaxis (e.g., during travel to
CHIKV-endemic regions) and treatment of CHIKV infections is urgently needed. We
here review some of the recently reported CHIKV inhibitors, both directly-acting
and host-targeting compounds.
PMID- 28414992
TI - Airway proteases: an emerging drug target for influenza and other respiratory
virus infections.
AB - To enter into airway epithelial cells, influenza, parainfluenza- and
coronaviruses rely on host cell proteases for activation of the viral protein
involved in membrane fusion. One protease, transmembrane protease serine 2
(TMPRSS2) was recently proven to be crucial for hemagglutinin cleavage of some
human influenza viruses. Since the catalytic sites of the diverse serine
proteases linked to influenza, parainfluenza- and coronavirus activation are
structurally similar, active site inhibitors of these airway proteases could have
broad therapeutic applicability against multiple respiratory viruses.
Alternatively, superior selectivity could be achieved with allosteric inhibitors
of TMPRSS2 or another critical protease. Though still in its infancy, airway
protease inhibition represents an attractive host-cell targeting approach to
combat respiratory viruses such as influenza.
PMID- 28414994
TI - Adapting the Body Appreciation Scale-2 for Children: A psychometric analysis of
the BAS-2C.
AB - Positive body image among adults is related to numerous indicators of well-being.
However, no research has explored body appreciation among children. To facilitate
our understanding of children's positive body image, the current study adapts and
validates the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a) for
use with children. Three hundred and forty-four children (54.4% girls) aged 9-11
completed the adapted Body Appreciation Scale-2 for Children (BAS-2C) alongside
measures of body esteem, media influence, body surveillance, mood, and dieting. A
sub-sample of 154 participants (62.3% girls) completed the questionnaire 6-weeks
later to examine stability (test-retest) reliability. The BAS-2C displayed a
unidimensional factor structure and evidence of internal consistency, test-retest
reliability, and construct, criterion-related, and incremental validity.
Additionally, the results suggest adaptive properties of body appreciation for
body-related and emotional well-being among children. The BAS-2C could serve as
an essential component within research to understand and estimate children's
positive body image.
PMID- 28414995
TI - Case report of an intracaval leiomyomatosis 10 months after complete
hysterectomy.
AB - INTRODUCTION: Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor,
usually found in women with tumors of the reproductive organs, such as uterus
myomatosous. Surgically, this case belies the call for sternotomy and two-stage
surgery in caval IVL extending to the right atrium: we suggest one-stage median
laparotomy as a minimal procedure with maximal benefit. PRESENTATION OF CASE: We
present the case of a 60-year-old postmenopausal woman with suspected intravenous
leiomyomatosis of the right internal iliac vein. The patient had undergone
hysterectomy and bilateral adnexectomy for uterus myomatosous in September 2015,
where an IVL limited to the veins of the uterus and the right adnex had been
diagnosed. No further medical treatment had been implemented. IVL of the inferior
vena cava was diagnosed when a CT scan of the abdomen was performed due to an
infected abdominal seroma in June 2016. Although histologically benign, we found
this case of IVL to be clinically aggressive because of its expansion to the
heart. This may lead to thromboembolic complications (e.g. pulmonary embolism) or
signs of right sided cardiac failure. The patient was asymptomatic, but because
of the extension of the intracaval thrombus to the heart, we decided to operate
and performed thrombectomy via a median laparotomy. The patient left the hospital
shortly after on newly started oral anticoagulation. DISCUSSION: For caval IVL
without intracardiac attachment, the extraction via laparotomy without sternotomy
is the treatment of choice. It calls for an interdisciplinary approach and
careful surgical planning. CONCLUSION: There is no inherent need for sternotomy
in IVL extending to the right atrium. A one-year follow-up with sonographic
control is advised. Medium term oral anticoagulation should be considered. This
work has been reported in line with the SCARE criteria Agha et al. (2016). The
SCARE Statement: Consensus-based surgical case report guidelines. Agha RA, Fowler
AJ, Saeta A, Barai I, Rajmohan S, Orgill DP; SCARE Group. Int J Surg. 2016
Oct;34:180-186 [1].
PMID- 28414996
TI - A case of multiple synchronous quadruple cancers of the stomach, sigmoid colon,
rectum, and pancreas.
AB - INTRODUCTION: Multiple primary neoplasms are relatively rare, but their incidence
has increased because of aging and improvements in diagnostic imaging.
PRESENTATION OF CASE: A 67-year-old man presented with epigastric pain. On upper
gastrointestinal endoscopy, an ulcer was seen at the gastric angle, and biopsy
showed moderately differentiated adenocarcinoma (AC). Colonoscopy demonstrated a
15-mm lesion in the sigmoid colon and a submucosal lesion in the lower rectum.
The biopsy showed well differentiated AC and neuroendocrine tumor (NET). In
addition, abdominal CT and MRI showed a 14-mm nodular lesion in the pancreatic
body suggesting pancreatic duct cancer. Based on the above findings, four
synchronous cancers, including the pancreas, stomach, sigmoid colon and rectum,
were diagnosed, and surgery was performed. A midline incision was made in the
upper abdomen, and a distal gastrectomy, pancreatic body and tail resection, and
sigmoidectomy were performed. Trans-anal tumor resection was performed for the
rectal lesion. Histopathology showed invasive pancreatic duct cancer, moderately
differentiated AC of the stomach, moderately differentiated AC of the sigmoid
colon, and NET G1 of the rectum. The patient had no postoperative complications,
4 years 3 months after resection, and he was disease-free from all of the
cancers. DISCUSSION: The strategy of perioperative diagnosis and treatment for
multiple primary tumors is usually difficult. This process was performed by
consulting a cancer board, which could be useful as a practice guideline.
CONCLUSION: This patient in whom four tumors were completely resected at the same
time and who has had a good clinical course was reported.
PMID- 28414997
TI - Successful treatment of nonocclusive mesenteric ischemia after aortic valve
replacement with continuous arterial alprostadil infusion: A case report.
AB - INTRODUCTION: Nonocclusive mesenteric ischemia (NOMI) after surgery has an
extremely poor prognosis with a mortality rate of 30-100%. We report a patient
with NOMI following aortic valve replacement who failed to improve despite
continuous intra-arterial infusion of papaverine, but was successfully treated
with alprostadil (prostaglandin E1 [PGE1]) infusion. PRESENTATION OF CASE: The
patient is a 77-year-old man who underwent aortic valve replacement. Due to
elevated serum lactate levels five hours after intensive care unit admission,
superior mesenteric arteriography was performed, establishing the diagnosis of
NOMI. Although continuous intra-arterial infusion of papaverine was begun,
lactate levels remained elevated. Repeat angiography and laparotomy revealed
extensive ischemic changes of the intestine. The vasodilator was changed to PGE1,
which improved arterial spasm. The patient ultimately needed an ileocecal
resection, but the extent of the resection was limited with concomitant PGE1
administration. DISCUSSION: In the present patient, although NOMI was
unresponsive to appropriate treatment including intra-arterial infusion of
papaverine, continuous intra-arterial infusion of PGE1 salvaged most of the
intestine. CONCLUSIONS: In a patient with recurrent NOMI despite appropriate
treatment including intra-arterial infusion of papaverine, continuous intra
arterial infusion of PGE1 may limit the extent of intestinal resection needed.
Continuous intra-arterial infusion of PGE1 may be a useful treatment for patients
with refractory NOMI.
PMID- 28414998
TI - A qualitative study on using concept maps in problem-based learning.
AB - BACKGROUND: The visual arts, including concept maps, have been shown to be
effective tools for facilitating student learning. However, the use of concept
maps in nursing education has been under-explored. OBJECTIVES: The aim of this
study was to explore how students develop concept maps and what these concept
maps consist of, and their views on the use of concept maps as a learning
activity in a PBL class. DESIGN: A qualitative approach consisting of an analysis
of the contents of the concept maps and interviews with students. SETTINGS: The
study was conducted in a school of nursing in a university in Hong Kong.
PARTICIPANTS: A total of 38 students who attended the morning session (20
students) and afternoon session (18 students) respectively of a nursing problem
based learning class. METHODS: The students in both the morning and afternoon
classes were allocated into four groups (4-5 students per group). Each group was
asked to draw two concept maps based on a given scenario, and then to participate
in a follow-up interview. Two raters individually assessed the concept maps, and
then discussed their views with each other. RESULTS: Among the concept maps that
were drawn, four were selected. Their four core features of those maps were: a)
the integration of informative and artistic elements; b) the delivery of
sensational messages; c) the use of images rather than words; and d) three
dimensional and movable. Both raters were concerned about how informative the
presentation was, the composition of the elements, and the ease of comprehension,
and appreciated the three-dimensional presentation and effective use of images.
From the results of the interview, the pros and cons of using concept maps were
discerned. CONCLUSIONS: This study demonstrated how concept maps could be
implemented in a PBL class to boost the students' creativity and to motivate them
to learn. This study suggests the use of concept maps as an initiative to
motivate student to learn, participate actively, and nurture their creativity. To
conclude, this study explored an alternative way for students to make
presentations and pioneered the use of art-based concept maps to facilitate
student learning.
PMID- 28414999
TI - Enhanced adsorption of bromate from aqueous solutions on ordered mesoporous Mg-Al
layered double hydroxides (LDHs).
AB - An ordered mesoporous Mg-Al layered double hydroxide (meso-LDH350) with a fairly
high Brunauer-Emmett-Teller (BET) surface area (126m2g-1) has been facilely
synthesized and then evaluated for the adsorptive removal of bromate from aqueous
solutions. Adsorbents were characterized by a variety of techniques (e.g., XRD,
FTIR, SEM, TG-DSC, N2 physisorption, XPS, etc.). The adsorption studies indicated
that the presence of background electrolytes and competitive anions can obviously
repress the uptake of bromate on LDHs. The adsorption isotherms agree well with
the Langmuir model, giving a maximum adsorption capacity of 59.34mgg-1 (pH 7.5,
10 degrees C) for meso-LDH350, which is much higher than other LDH-type
adsorbents reported in literature. The adsorption kinetic data can be well fitted
with the pseudo-second-order rate model. Based on the macroscopic and microscopic
studies, bromate adsorption on meso-LDH350 was associated with two mechanisms:
the reconstruction of the layered structures of meso-LDH350 and the anion
exchange between bromate and the intercalated anions.
PMID- 28415000
TI - Changes in copper toxicity towards diatom communities with experimental warming.
AB - Biological communities in aquatic environments most commonly face multiple
stress, where natural and anthropogenic stressors often act jointly. Their
interactions are most easily assessed using short cycle organisms such as
periphytic diatoms. In this experiment, we analyzed the combined effects of
copper exposure and warming on diatom successions over 6 weeks. Natural biofilm
collected in winter was left to grow in mesocosms exposed or unexposed to
realistic Cu concentrations at four different temperatures. Separate and joint
impacts of the two stressors were determined through structural and functional
endpoints. Both temperature and copper influenced the biological responses; their
interaction, when significant, was always antagonistic. Diatom communities
gradually changed with rising temperature. Under copper exposure, the dominant
Planothidium lanceolatum was superseded by Achnanthidium exiguum, which accounted
for about 70% relative abundance in the warmest conditions (18-23 degrees C).
Tolerance to copper was derived from dose-response curves based on photosynthesis
inhibition. Cu-induced community tolerance was always found, but it decreased
with warming and time. Biodiversity loss associated with lower Cu tolerance under
combined Cu exposure and increasing temperatures evidences the major influence of
cumulative stressors on aquatic health. These results highlight the crucial
interplay between environmental stressors, which are expected to intensify with
climate change.
PMID- 28415001
TI - Degradation of synthetic fragrances by laccase-mediated system.
AB - Laccase mediator systems are important biodegradation agents as the rate of
reaction could be enhanced in the presence of redox mediators. In the present
study the commercial enzyme laccase from Trametes versicolor and the redox
mediator 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) were used
for the biotransformation of the synthetic fragrances 1-(1,2,3,4,5,6,7,8
octahydro-2,3,8,8,-tetramethyl-2-naphthyl)ethan-1-one (Iso-E-Super, OTNE),
1,3,4,6,7,8,-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyran
(Galaxolide, HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtalene
(Tonalide, AHTN) and the transformation product of HHCB, 1,3,4,6,7,8-hexahydro
4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyran-1-one (Galaxolidone, HHCB
lactone) in water. A particular focus was to assess the effects of the enzyme
laccase from Trametes versicolor in the enantioselective degradation of the
target compounds, for this reason gas chromatography with an enantioselective
column was used as separation technique followed by mass spectrometry detection.
In addition, as enantioselective degradation of musk fragrances was observed in
wastewater, sewage sludge and fish samples, enantiomeric fractions of selected
compounds were studied during composting. In a period of 144h, the target
fragrances could be effectively removed by the enzyme laccase with removal
percentages greater than 70%, except AHTN with a removal percentage of 42%.
However, the degradation process prompted by the enzyme laccase was shown to be
non-enantioselective as no significant differences were observer between the
enantiomeric fractions calculated at the beginning and at the end of the
degradation process. Meanwhile, the composting process was shown to be
enantioselective.
PMID- 28415002
TI - Experimental and numerical study of liquefied natural gas (LNG) pool spreading
and vaporization on water.
AB - The investigation of pool spreading and vaporization phenomenon is an essential
part of consequence analysis to determine the severity of LNG spills on water. In
this study, release of LNG on water during marine operations is studied through
experimental and numerical methods The study involves emulation of an LNG leak
from transfer arms during side by side loading operations. The experimental part
involves flow of LNG in a narrow trench filled with water and subsequent
measurement of pool spreading and vaporization parameters. The numerical part
involves CFD simulation using a three dimensional hybrid homogenous Eulerian
multiphase solver to model the pool spreading and vaporization phenomenon. In
this method, LNG is modeled as dispersed phase droplets which can interact with
continuous phases - water and air through interphase models. The numerical study
also employs a novel user-defined routine for capturing the LNG vaporization
process. The CFD solver was capable of capturing the salient features of LNG pool
spreading and vaporization phenomena. It was observed from experiment and CFD
simulation that wind influenced both pool spreading and vaporization phenomenon
through entrainment and convection.
PMID- 28415003
TI - Less-favourable prognosis for low-risk endometrial cancer patients with a
discordant pre- versus post-operative risk stratification.
AB - BACKGROUND: Pre-operative risk stratification based on endometrial sampling
determines the extent of surgery for endometrial cancer (EC). We investigated the
concordance of pre- and post-operative risk stratifications and the impact of
discordance on survival. METHODS: Patients diagnosed with EC within the first 6
months of the years 2005-2014 were selected from the Netherlands Cancer Registry
(N = 7875). Pre- and post-operative risk stratifications were determined based on
grade and/or histological subtype for 3784 eligible patients. RESULTS: A
discordant risk stratification was found in 10% of patients: 4% (N = 155) had
high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post
operative risk. Overall survival of patients with high pre- and low post
operative risk was less favourable compared to those with a concordant low risk
(80% versus 89%, p = 0.002). This difference remained significant when correcting
for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95%
confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre- and
high post-operative risk did not differ from those with a concordant high risk
(64% versus 62%, p = 0.295). CONCLUSION: Patients with high pre- and low post
operative risk have a less favourable prognosis compared to patients with a
concordant low risk. Pre-operative risk stratifications contain independent
prognostic information and should be incorporated into clinical decision-making.
PMID- 28415004
TI - Types of household humidifier disinfectant and associated risk of lung injury
(HDLI) in South Korea.
AB - From 2002 through 2015, hundreds of people died of fatal lung injuries associated
with the use of humidifier disinfectants (HDs) in Korea. Several chemical
disinfectants used for household humidifiers were later clinically confirmed to
cause HD-associated lung injury (HDLI). The aim of this study is to evaluate the
registered lung disease cases and to compare the distribution of HDLI patients,
including deaths, by HD use characteristics including types of HD and HD brands
categorized by age group. A total of 530 registered were clinically examined
through two rounds of investigations conducted from July 2013 until April 2015.
Information on HD use was obtained from a structured questionnaire and home
investigations. Approximately one-half of the patients (n=221) were clinically
confirmed to be associated with the use of HDs. Pregnant women (n=35, 16%) and
pre-school children<=6years old (n=128, 58%) accounted for most of the HD
associated lung injury patients (n=163, 74%). Sixty-seven percent of HDLI
patients developed HDLI after less than one year of HD use. HD products
containing polyhexamethylene guanidine phosphate (PHMG) were the most frequently
used among confirmed HDLI patients (n=123, 55.7%), followed by oligo (2-(2
ethoxy) ethoxyethyl guanidinium (PGH) (n=24, 10.9%) and a mixture of
chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) (n=3, 1.4%).
Other HDs did not appear to be linked to HDLI. The majority of the HDLI patients
(n=85, 38.5%) was found to use only Oxy Saksak(r) products containing PHMG. The
development of HDLI was clinically found to be associated with the use of several
HD products containing PHMG and PGH, and to lesser extent, CMIT/MIT.
PMID- 28415005
TI - Agricultural sustainable intensification improved nitrogen use efficiency and
maintained high crop yield during 1980-2014 in Northern China.
AB - Global population increase will require rapid increase of food production from
existing agricultural land by 2050, which will inevitably mean the increase of
agricultural productivity. Due to agricultural sustainable intensification since
the 1990s, crop production in Huantai County of northern China has risen to 15tha
1yr-1 for the annual wheat-maize rotation system. We examined the temporal
dynamics of nitrogen (N) budget, N losses, and N use efficiency (NUE) during the
35years (1980-2014) in Huantai. The results revealed that atmospheric N
deposition increased 220% while reactive N losses decreased by 21.5% from 1980s
to 2010s. During 1980-2002, annual N partial factor productivity (PFPN), apparent
NUE and N recovery efficiency (REN) increased from 20.3 to 40.7kggrainkg-1Nfert,
from 36.5% to 71.0%, and from 32.4% to 57.7%, respectively; meanwhile, reactive N
losses intensity, land use intensity and N use intensity decreased by 69.8%,
53.4%, 50.0%, respectively, but without further significant changes after 2002.
Overall increases in NUE and decreases in N losses were largely due to the
introduction of optimized fertilization practice, mechanization and increased
incorporation of crop straw in Huantai. Straw incorporation was also significant
in soil N stock accrual and fertility improvement. By 2030, northern China may
reach the lowest end of PFPN values in developed countries (>45kggrainkg-1Nfert).
These agricultural sustainable intensification practices will be critical in
maintaining high grain yields and associated decreases in environmental
pollution, although water use efficiency in the region still needs to be
improved.
PMID- 28415006
TI - Accumulation of nonessential trace elements (Ag, As, Cd, Cr, Hg and Pb) in
Atlantic horseshoe crab (Limulus polyphemus) early life stages.
AB - During early development, benthic organisms can accumulate nonessential trace
elements through aqueous and particulate sources. This study investigated the
accumulation of Ag, As, Cd, Cr, Hg and Pb in Atlantic horseshoe crab (Limulus
polyphemus) pre-spawned eggs, embryos, and developing larvae collected from 5
sites on Long Island, NY and compared these concentrations to that found in
sediment, pore water, and overlying water. All investigated elements were
detected in embryos and larvae at all sites. Arsenic was found at the highest
concentration in each life stage across all 5 sites, followed by Ag, whereas Cd,
Hg and Pb concentrations varied between sites. Chromium was not detected in pre
spawned eggs, but was present in embryos and larvae at all sites, however, along
with Hg, significantly increased from embryo to larvae at most sites. We conclude
that observed accumulation patterns are likely a result of abiotic factors,
differences in uptake pathways between life stages and the rate of excretion.
Future laboratory studies are required to understand the factors influencing the
aqueous and dietary uptake of nonessential trace elements in the early life
stages of Atlantic horseshoe crabs.
PMID- 28415007
TI - Religion, spirituality, and mental health of U.S. military veterans: Results from
the National Health and Resilience in Veterans Study.
AB - BACKGROUND: In the last three decades, there has been increased interest in
studying the association between religion/spirituality (R/S), and mental health
and functional outcomes. METHODS: Using data from a contemporary, nationally
representative sample of 3151 U.S. military veterans maintained by GfK Knowledge
Networks, Inc., we evaluated the relation between R/S and a broad range of mental
health, and psychosocial variables. Veterans were grouped into three groups based
on scores on the Duke University Religion Index: High R/S (weighted 11.6%),
Moderate R/S (79.7%) and Low R/S (8.7%). RESULTS: A "dose-response" protective
association between R/S groups and several mental health outcomes was revealed,
even after adjustment for sociodemographic and military variables. High R/S was
associated with decreased risk for lifetime posttraumatic stress disorder (odds
ratio [OR]=0.46), major depressive disorder (MDD; OR=0.50), and alcohol use
disorder (OR=0.66), while Moderate R/S was associated with decreased risk for
lifetime MDD (OR=0.66), current suicidal ideation (OR=0.63), and alcohol use
disorder (OR=0.76). Higher levels of R/S were also strongly linked with increased
dispositional gratitude, purpose in life, and posttraumatic growth. LIMITATIONS:
In this cross-sectional study, no conclusions regarding causality can be made.
The study provides a current snapshot of the link between R/S and mental health.
The study also cannot determine whether religious coping styles (negative vs
positive coping) contributed to observed differences. CONCLUSIONS: Although the
present study does not have treatment implications, our results suggest that
higher levels of R/S may help buffer risk for certain mental disorders and
promote protective psychosocial characteristics in U.S. military veterans.
PMID- 28415008
TI - Bipolar mood state reflected in cortico-amygdala resting state connectivity: A
cohort and longitudinal study.
AB - BACKGROUND: Using resting-state functional magnetic resonance imaging (rsfMRI),
we previously compared cohorts of bipolar I subjects in a manic state to those in
a euthymic state to identify mood state-specific patterns of cortico-amygdala
connectivity. Our results suggested that mania is reflected in the disruption of
emotion regulation circuits. We sought to replicate this finding in a group of
subjects with bipolar disorder imaged longitudinally across states of mania and
euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged
in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged
longitudinally across both mood states. We measured differences in amygdala
connectivity between the mania and euthymia cohorts. We then used these regions
of altered connectivity to examine connectivity in the longitudinal bipolar group
using a within-subjects design. RESULTS: Our findings in the mania vs euthymia
cohort comparison were replicated in the longitudinal analysis. Bipolar mania was
differentiated from euthymia by decreased connectivity between the amygdala and
pre-genual anterior cingulate cortex. Mania was also characterized by increased
connectivity between amygdala and the supplemental motor area, a region normally
anti-correlated to the amygdala in emotion regulation tasks. LIMITATIONS:
Stringent controls for movement effects limited the number of subjects in the
longitudinal sample. CONCLUSIONS: In this first report of rsfMRI conducted
longitudinally across mood states, we find that previously observed between-group
differences in amygdala connectivity are also found longitudinally within
subjects. These results suggest resting state cortico-amygdala connectivity is a
biomarker of mood state in bipolar disorder.
PMID- 28415009
TI - Selective HDAC inhibitors with potent oral activity against leukemia and
colorectal cancer: Design, structure-activity relationship and anti-tumor
activity study.
AB - Previously, we reported the discovery of a series of N-hydroxycinnamamide-based
HDAC inhibitors, among which compound 11y exhibited high HDAC1/3 selectivity. In
this current study, structural derivatization of 11y led to a new series of
benzamide based HDAC inhibitors. Most of the compounds exhibited high HDACs
inhibitory potency. Compound 11a (with 4-methoxybenzoyl as N-substituent in the
cap and 4-(aminomethyl) benzoyl as the linker group) exhibited selectivity
against HDAC1 to some extent, and showed potent antiproliferative activity
against several tumor cell lines. In vivo studies revealed that compound 11a
displayed potent oral antitumor activity in both hematological tumor cell U937
xenograft model and solid tumor cell HCT116 xenograft model with no obvious
toxicity. Further modification of benzamide 3, 11a and 19 afforded new thienyl
and phenyl compounds (50a, 50b, 63a, 63b and 63c) with dramatic HDAC1 and HDAC2
dual selectivity, and the fluorine containing compound 56, with moderate HDAC3
selectivity.
PMID- 28415010
TI - Structure and biological properties of mixed-ligand Cu(II) Schiff base complexes
as potential anticancer agents.
AB - We synthesized two mixed-ligand Cu(II) complexes containing different
aroylhydrazone ligands and a pyridine co-ligand, namely, [Cu(L1)(Py)] (C1) and
[Cu(L2)(Py)(Br)] (C2) (L1 = (E)-2-hydroxy-N'-((2-hydroxynaphthalen-1
yl)methylene)benzohydrazide, Py = pyridine, L2 = (E)-2-hydroxy-N'-(phenyl(pyridin
2-yl)methylene)benzohydrazide), and assessed their chemical and biological
properties to understand their marked activity. C2 showed better anticancer
activity than C1 in various human cancer cell lines, including the cisplatin
resistant lung cancer cell line A549cisR. Both Cu(II) complexes, especially C2,
displayed promising anti-metastatic activity against HepG2 cells. Spectroscopic
titration and agarose gel electrophoresis experiments indicated that C2 exhibited
binding affinity toward calf-thymus DNA and efficient pBR322 DNA-cleaving
ability. Further mechanistic studies showed that C2 effectively induced DNA
damage and thus led to cell cycle arrest at the G2/M phase, and also stimulated
mitochondrial dysfunction mediated by reactive oxygen species and caspase
dependent apoptosis.
PMID- 28415011
TI - Design and synthesis of novel xanthine derivatives as potent and selective A2B
adenosine receptor antagonists for the treatment of chronic inflammatory airway
diseases.
AB - Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics
through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists
have been shown to attenuate airway reactivity and improve inflammatory
conditions in pre-clinical studies. Hence, the identification of novel, potent
and selective A2BAdoR antagonist may be beneficial for the potential treatment of
asthma and Chronic Obstructive Pulmonary Disease (COPD). Towards this effort, we
explored several prop-2-ynylated C8-aryl or heteroaryl substitutions on xanthine
chemotype and found that 1-prop-2-ynyl-1H-pyrazol-4-yl moiety was better
tolerated at the C8 position. Compound 59, exhibited binding affinity (Ki) of 62
nM but was non-selective for A2BAdoR over other AdoRs. Incorporation of
substituted phenyl on the terminal acetylene increased the binding affinity (Ki)
significantly to <10 nM. Various substitutions on terminal phenyl group and
different alkyl substitutions on N-1 and N-3 were explored to improve the
potency, selectivity for A2BAdoR and the solubility. In general, compounds with
meta-substituted phenyl provided better selectivity for A2BAdoR compared to that
of para-substituted analogs. Substitutions such as basic amines like pyrrolidine,
piperidine, piperazine or cycloalkyls with polar group were tried on terminal
acetylene, keeping in mind the poor solubility of xanthine analogs in general.
However, these substitutions led to a decrease in affinity compared to compound
59. Subsequent SAR optimization resulted in identification of compound 46 with
high human A2BAdoR affinity (Ki = 13 nM), selectivity against other AdoR subtypes
and with good pharmacokinetic properties. It was found to be a potent functional
A2BAdoR antagonist with a Ki of 8 nM in cAMP assay in hA2B-HEK293 cells and an
IC50 of 107 nM in IL6 assay in NIH-3T3 cells. Docking study was performed to
rationalize the observed affinity data. Structure-activity relationship (SAR)
studies also led to identification of compound 36 as a potent A2BAdoR antagonist
with Ki of 1.8 nM in cAMP assay and good aqueous solubility of 529 MUM at neutral
pH. Compound 46 was further tested for in vivo efficacy and found to be
efficacious in ovalbumin-induced allergic asthma model in mice.
PMID- 28415012
TI - Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives
as new potent and selective human sirtuin 2 inhibitors.
AB - Human sirtuin 2 (SIRT2) plays pivotal roles in multiple biological processes such
as cell cycle regulation, autophagy, immune and inflammatory responses.
Dysregulation of SIRT2 was considered as a main aspect contributing to several
human diseases, including cancer. Development of new potent and selective SIRT2
inhibitors is currently desirable, which may provide a new strategy for treatment
of related diseases. Herein, a structure-based optimization approach led to new 2
((4,6-dimethylpyrimidin-2-yl)thio)-N-phenylacetamide derivatives as SIRT2
inhibitors. SAR analyses with new synthesized derivatives revealed a number of
new potent SIRT2 inhibitors, among which 28e is the most potent inhibitor with an
IC50 value of 42 nM. The selectivity analyses found that 28e has a very good
selectivity to SIRT2 over SIRT1 and SIRT3. In cellular assays, 28e showed a
potent ability to inhibit human breast cancer cell line MCF-7 and increase the
acetylation of alpha-tubulin in a dose-dependent manner. This study will aid
further efforts to develop highly potent and selective SIRT2 inhibitors for the
treatment of cancer and other related diseases.
PMID- 28415013
TI - The effect of exercise on fatigue and physical functioning in breast cancer
patients during and after treatment and at 6 months follow-up: A meta-analysis.
AB - Breast cancer is the leading cause of cancer in women worldwide. Exercise
interventions may improve physical and psychological factors during and after
active breast cancer treatment. The aim of this systematic review was to assess
the current knowledge regarding the efficacy of physical exercise with respect to
fatigue and self-reported physical functioning. Systematic searches in Cochrane
Library, Medline, Embase, Cinahl, PsycINFO, AMED and PEDro. After assessing the
quality of the studies, we identified 25 randomized controlled trials that
included 3418 breast cancer patients. An increase in physical functioning and a
decrease in fatigue were observed after a physical exercise intervention, with an
SMD of 0.27 (0.12, 0.41) and -0.32 (-0.49, - 0.14), respectively. There were
slightly higher improvements in physical functioning and fatigue when the
patients received the intervention after adjuvant breast cancer treatment. The 6
month follow-up data showed a small favourable difference for the physical
exercise group for both physical functioning and fatigue. This systematic review
found that an exercise intervention program can produce short-term improvements
in physical functioning and can reduce fatigue in breast cancer patients.
However, more studies are needed to confirm the time-dependent observations in
this study.
PMID- 28415014
TI - Determination and quantification of intracellular fludarabine triphosphate,
cladribine triphosphate and clofarabine triphosphate by LC-MS/MS in human cancer
cells.
AB - Purine nucleoside analogues are widely used in the treatment of haematological
malignancies, and their biological activity is dependent on the intracellular
accumulation of their triphosphorylated metabolites. In this context, we
developed and validated a liquid chromatography tandem mass spectrometry (LC
MS/MS) method to study the formation of 5'-triphosphorylated derivatives of
cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells.
Br-ATP was used as internal standard. Separation was achieved on a hypercarb
column. Analytes were eluted with a mixture of hexylamine (5 mM), DEA (0.4%, v/v,
pH 10.5) and acetonitrile, in a gradient mode at a flow rate of 0.3mLmin-1.
Multiple reactions monitoring (MRM) and electrospray ionization in negative mode
(ESI-) were used for detection. The application of this method to the
quantification of these phosphorylated cytotoxic compounds in a human follicular
lymphoma cell line, showed that it was suitable for the study of relevant
biological samples.
PMID- 28415016
TI - An LC-MS/MS method for the determination of antibiotic residues in distillers
grains.
AB - Antibiotics are used in ethanol production to discourage the growth of bacteria
that would result in lower ethanol content and a lower quality product. A survey
conducted by the FDA (FY 2010 Nationwide Survey of Distillers Grains for
Antibiotic Residues, 2009 [1]) revealed that the residues of these antibiotics
can remain in the distillers grains (DG) by-product, which is used as an animal
feed ingredient. The low levels of antibiotic residues in DG could be a public
health concern, as they could lead to antimicrobial resistance. To enable the
quantitative determination of these antibiotics (erythromycin, penicillin G,
virginiamycin M1 and virginiamycin S1), we developed a sensitive LC-MS/MS method.
The residues were extracted from distillers grains with a mixture of acetonitrile
and buffer followed by acetonitrile. The combined extract was diluted with water
and washed with hexane. An aliquot was cleaned up on an Oasis HLB solid phase
extraction cartridge. Extracts were analyzed by LC-tandem mass spectrometry. The
method was successfully validated using a variety of different matrices such as
corn DG, corn & milo DG, and deoiled corn DG. Absolute recoveries of the analytes
ranged from 53 to 106%. Accuracy ranged from 90 to 101% based on calibration by
matrix standards. The limits of quantitation and relative standard deviation were
all satisfactory to support future surveillance studies.
PMID- 28415015
TI - Lipidomics by ultrahigh performance liquid chromatography-high resolution mass
spectrometry and its application to complex biological samples.
AB - An improved approach for selective and sensitive identification and quantitation
of lipid molecular species using reversed phase chromatography coupled to high
resolution mass spectrometry was developed. The method is applicable to a wide
variety of biological matrices using a simple liquid-liquid extraction procedure.
Together, this approach combines multiple selectivity criteria: Reversed phase
chromatography separates lipids according to their acyl chain length and degree
of unsaturation and is capable of resolving positional isomers of
lysophospholipids, as well as structural isomers of diacyl phospholipids and
glycerolipids. Orbitrap mass spectrometry delivers the elemental composition of
both positive and negative ions with high mass accuracy. Finally, automatically
generated tandem mass spectra provide structural insight into numerous
glycerolipids, phospholipids, and sphingolipids within a single run. Calibration
showed linearity ranges of more than four orders of magnitude, good values for
accuracy and precision at biologically relevant concentration levels, and limits
of quantitation of a few femtomoles on column. Hundreds of lipid molecular
species were detected and quantified in three different biological matrices,
which cover well the wide variety and complexity of various model organisms in
lipidomic research. Together with a software package, this method is a prime
choice for global lipidomic analysis of even the most complex biological samples.
PMID- 28415017
TI - Accelerated solvent extraction method for the quantification of polycyclic
aromatic hydrocarbons in cocoa beans by gas chromatography-mass spectrometry.
AB - An accelerated solvent extraction (ASE) procedure for use with gas chromatography
mass spectrometry (GC-MS) was optimized for the determination of eight polycyclic
aromatic hydrocarbons (PAHs) in cocoa beans. Plackett-Burman and rotatable
central composite design (RCCD) indicated that three variables affected the
recoveries of PAHs during the extraction and purification steps: agitation time
in the second liquid-liquid partition, weight of silica gel in the column, and
volume of hexane for PAH elution from the column. After obtaining the optimal
conditions, a single laboratory method validation was performed. Linearity was
demonstrated for benzo[a]pyrene in the concentration range from 0.5 to 8.0mgkg-1
of sample, corresponding to 1.25-20.0MUgkg-1 of cocoa on a fat basis. For the
other analytes, linearity was observed from 0.75 to 8.0MUgkg-1 of sample (1.88
20.0MUgkg-1 of cocoa on a fat basis). Significant matrix effects were found for
chrysene and benzo[b]fluoranthene. The precision of the method was verified with
relative standard deviations (RSDs) ranging from 2.57 to 14.13% and from 4.36 to
19.77% under repeatability and intermediate precision conditions, respectively.
The average recoveries of the eight PAHs ranged from 74.99 to 109.73%. These
parameters, limits and measurement uncertainties met the performance criteria
established by European Union regulations, except for the theoretical limit of
detection for chrysene. The method was applied to the analysis of samples of
Brazilian cocoa beans, and only one sample was found to have a PAH content above
the maximum limit defined by the European Union legislation. This optimized and
validated method is intended to be used as part of the official Brazilian
monitoring programs investigating contaminants and residues in food.
PMID- 28415018
TI - Internal consistency and concurrent validity of the Montreal Cognitive Assessment
in individuals with major depressive disorder.
AB - This study aimed to determine the internal consistency and concurrent validity of
the Montreal Cognitive Assessment (MoCA), as well as its subtests, in patients
with major depressive disorder (MDD). Participants were patients with DSM-IV MDD
aged between 21 and 65 years. Neurocognitive function was assessed by using the
MoCA and 12 neurocognitive tests. The composite z-score of 12 neurocognitive
tests, which indicated the global cognitive performance, was calculated.
Participants were 57 outpatients with MDD. Except the MoCA Orientation, each of
the MoCA subtests showed a wide range of scores. The average inter-item
correlation and the Cronbach's alpha of MoCA were 0.24 and 0.64, respectively.
The MoCA total score was significantly and highly associated with the composite z
score of 12 neurocognitive tests (Pearson's r=0.78, p<0.001). The score of each
MoCA subtest was significantly and moderately correlated with the z-score of its
analogous neuropsychological test (absolute Spearman's rs's=0.33-0.56,
p's<=0.01). The MoCA and its subtests are reliable and valid for assessing global
and specific cognitive performance in patients with MDD and could be a tool for
screening neurocognitive deficits in depressed patients.
PMID- 28415019
TI - Recovery of infective virus particles in ion-exchange and hydrophobic interaction
monolith chromatography is influenced by particle charge and total-to-infective
particle ratio.
AB - Viral particles are used in medical applications as vaccines or gene therapy
vectors. In order to obtain product of high purity, potency and safety for
medical use purification of virus particles is a prerequisite, and chromatography
is gaining increased attention to meet this aim. Here, we report on the use of
ion-exchange and hydrophobic interaction chromatography on monolithic columns for
purification of mumps virus (MuV) and measles virus (MeV). Efficiency of the
process was monitored by quantification of infective virus particles (by 50% cell
culture infective dose assay) and total virus particles, and monitoring of their
size (by Nanoparticle Tracking Analysis). Ion-exchange chromatography was shown
to be inefficient for MuV and best results for MeV were obtained on QA column
with recovery around 17%. Purification of MuV and MeV by hydrophobic interaction
chromatography resulted in recoveries around 60%. Results showed that columns
with small channels (d=1.4MUm) are not suitable for MuV and MeV, although their
size is below 400nm, whereas columns with large channels (6MUm) showed to be
efficient and recoveries independent on the flow rate up to 10mL/min.
Heterogeneity of the virus suspension and its interday variability mostly
regarding total-to-infective particle ratio was observed. Interestingly, a trend
in recovery depending on the day of the harvest was also observed for both
viruses, and it correlated with the total-to-infective particle ratio, indicating
influence of the virus sample composition on the chromatography results.
PMID- 28415020
TI - Simultaneous determination of ten bioactive constituents of Sanjie Zhentong
Capsule in rat plasma by ultra-high-performance liquid chromatography tandem mass
spectrometry and its application to a pharmacokinetic study.
AB - Sanjie Zhentong capsule, a well-known traditional Chinese medicine prescription,
are used for the treatment of endometriosis-related diseases. In this study, a
simple, rapid and sensitive ultra-high-performance liquid chromatography-tandem
mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous
determination of ten bioactive constituents, including peimine, peiminine,
peimisine, loureirin A, loureirin B, 7,4'-dihydroxyflavone, pterostilbene,
ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 in rat plasma after oral
administration of Sanjie Zhentong capsule. The sample preparations for protein
removal was accomplished using a simple methanol precipitation method. The
analytes were completely separated from the endogenous compounds on an Agilent
Poroshell 120 SB-C18 column (4.6mm*150mm, 2.7MUm) using an isocratic elution with
methanol - 0.1% formic acid aqueous (4/1, v/v) as a mobile phase. The single-run
analysis time was as short as 14.0min. The inter-day and intra-day precision of
the quality control samples exhibited relative standard deviations (RSD) <9.5%
and the accuracy values ranged from -8.6% to 15.0%. The lower limits of
quantification (LLOQ) were 10, 10, 10, 10, 10, 10, 5, 10, 10 and 20ng/mL for
peimine, peiminine, peimisine, loureirin A, loureirin B, 7,4'-dihydroxyflavone,
pterostilbene, ginsenoside Rg1, ginsenoside Rb1, notoginsenoside R1,
respectively. The analytical method was successfully applied to a pharmacokinetic
study of the multi-components after oral administration of Sanjie Zhentong
Capsule in rats.
PMID- 28415021
TI - In vitro Investigation of Metabolic Profiling of a Potent Topoisomerase
Inhibitors Fluorescein Hydrazones (FLHs) in RLMs by LC-MS/MS.
AB - Metabolic profiling of newly reported two topoisomerase inhibitors namely
fluorescein hydrazones (FLHs) were studied in rat liver microsomes (RLMs) and the
data were acquired in a liquid chromatography (LC) ion trap mass spectrometry.
(E)-3',6'-dihydroxy-2-((2-nitrobenzylidene)amino)spiro[isoindoline-1,9'-xanthen]
3-one (1) was bio-transformed into two mono-hydroxylated, one double hydroxylated
and a tetra hydroxylated metabolites, on the other hand, (Z)-3',6'-dihydroxy-2
((2-oxoindolin-3-ylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (2) was bio
transformed into eight possible metabolites by cleavage reduction, hydroxylation,
cleavage reduction together with hydroxylated and azo-reduction in RLMs in
presence of NADPH-generating system. No metabolites were generated in the absence
of either NADPH or microsomes for the compounds (1 and 2), indicating a likely
involvement of CYP450 enzymes and the cofactor NADPH in the metabolisms. The
structures of those metabolite were elucidated by MS/MS fragmentation study.
PMID- 28415022
TI - Simultaneous determination of tryptophan and 8 metabolites in human plasma by
liquid chromatography/tandem mass spectrometry.
AB - Tryptophan (Trp) is an essential amino-acid and the precursor of many
biologically active substances such as kynurenine (KYN) and serotonin (5HT). Its
metabolism is involved in different physiopathological states, such as
cardiovascular diseases, cancer, immunomodulation or depression. Hence, the
quantification of Trp catabolites, from both KYN and 5HT pathways, might be
usefulfor the discovery of novel diagnostic and follow-up biomarkers. We have
developed a simple method for quantification of Trp and 8 of its
metabolites,involved in both KYN and 5HT pathways, using liquid chromatography
coupled to tandem mass spectrometry. We also validated the methodin human plasma
samples, according to NF EN ISO 15189 criteria. Our method shows acceptable intra
and inter-day coefficients of variation (CV) (<12% and <16% respectively). The
linearity entirelycovers the human plasma range. Stabilities of whole blood and
of residues weredetermined, as well as the use of 2 different types of
collectiontube, enabling us to adapt our process. Matrix effects and reference
values showed good agreement compared to the literature. We propose here a method
allowing the simultaneous quantification of a panel of Trp catabolites, never
used before to our knowledge. This method, witha quickchromatographic runtime
(15min) and simple sample preparation, has beenvalidated according to NF EN ISO
15189 criteria. The method enables the detailed analysis of these metabolic
pathways, which are thought to be involved in a number of pathological
conditions.
PMID- 28415023
TI - Drosophila models of prionopathies: insight into prion protein function,
transmission, and neurotoxicity.
AB - Prion diseases (PrD) are unique neurodegenerative conditions with sporadic,
genetic, and infectious etiologies. The agent responsible for these pathologies
is a misfolded conformation of the prion protein (PrP). Although a process of
autocatalytic "conversion" is known to mediate disease transmission, important
gaps still remain regarding the physiological function of PrP and its relevance
to pathogenesis, the molecular and cellular mechanisms mediating neurotoxicity
and transmission, and the PrP conformations responsible for neurotoxicity. New
Drosophila models expressing mammalian PrP have revealed physiological insight
into PrP function and opened the door to significant progress in prion
transmission and PrP neurotoxicity. Importantly, flies expressing human PrP
showing a robust eye phenotype will allow performing genetic screens to uncover
novel mechanisms mediating PrP neurotoxicity.
PMID- 28415024
TI - Glucocorticoids differentially regulate the innate immune responses of TLR4 and
the cytosolic DNA sensing pathway.
AB - Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders
because of their powerful anti-inflammatory properties; however, their effects on
macrophage-mediated immune responses are not completely understood. In the
present study, we found that GCs decreased LPS-mediated TBK1 activation and the
expression of IFN-beta, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1
activity and cytokine expression were not affected by GCs treatment. Furthermore,
GCs decreased the expression of key autophagy-related genes (ATGs), including
ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS
stimulation. However, GCs had no effect on poly(dA:dT)-mediated autophagy and ATG
expression in macrophages. Collectively, this study demonstrates that GCs inhibit
the TLR4-mediated innate immune response, but do not affect the cytosolic DNA
sensing pathway. This provides new insights into the immunomodulatory mechanisms
of GCs in macrophages, which may provide useful information for the clinical use
of GCs in treating chronic inflammatory disorders.
PMID- 28415025
TI - Unusual combination of femoral head dislocation associated acetabular fracture
with multipart femoral fractures: Case report.
AB - INTRODUCTION: Traumatic hip dislocation associated with femur intertrocanteric
fracture is a rare and severe injury and it frequently occurs following a high
energy trauma, Associated acetabular fractures with this injury are even more
rare and potentially cause devastating consequences including avascular necrosis
of the femoral head and subsequent early secondary osteoarthritis of the hip
joint. PRESENTATION OF CASE: In this case report, we present a 20year old
polytraumatized patient with traumatic hip dislocation associated with
ipsilateral acetabulum fracture and simultaneous fractures of the ipsilateral
femur. DISCUSSION: Traumatic hip dislocation associated with femur
intertrochanteric fracture is a rare and severe injury and it frequently occurs
following a high energy trauma. In polytraumatized patients, musculoskeletal
injuries are the most common lesions requiring surgical intervention frequently
presenting challenging scenarios in terms of functional outcome and quality of
life. Osteonecrosis of the femoral head is a serious and unpredictable
complication that may occur after displaced femoral neck fracture and traumatic
hip dislocation due to the disturbed blood supply of the femoral head.
CONCLUSION: A staged treatment strategy may be useful managing an unstable
polytraumatized patient or a patient who requires prolonged transfer to receive
definitive care.
PMID- 28415026
TI - Effects of carbon nanotubes on phosphorus adsorption behaviors on aquatic
sediments.
AB - Aquatic sediments are believed to be an important sink for carbon nanotubes
(CNTs). With novel properties, CNTs can potentially disturb the fate and mobility
of the co-existing contaminants in the sediments. Only toxic pollutants have been
investigated previously, and to the best of our knowledge, no data has been
published on how CNTs influence phosphorus (P) adsorption on aquatic sediments.
In this study, multi-walled carbon nanotubes (MWCNTs) were selected as model
CNTs. Experimental results indicated that compared to pseudo-first order and
intraparticle diffusion models, the pseudo-second-order model is better for
describing the adsorption kinetics of sediments and MWCNT-contaminated sediments.
Adsorption isotherm studies suggested that the Langmuir model fits the isotherm
data well. With the increase in the MWCNT-to-sediment ratio from 0.0% to 5.0%,
the theoretical maximum monolayer adsorption capacity (Qmax) for P increased from
0.664 to 0.996mg/g. However, the Langmuir isotherm coefficient (KL) significantly
decreased from 4.231L/mg to 2.874L/mg, indicating the decrease in the adsorption
free energy of P adsorbed on the sediments after MWCNT contamination. It was
suggested that P was released more easily to the overlying water after the re
suspension of sediments. Moreover, the adsorption of sediments and sediment-MWCNT
mixture was endothermic and physical in nature. Results obtained herein suggested
that the change in the specific surface area and zeta potential of sediments is
related to MWCNT contamination, and the large adsorption capacity of MWCNTs is
probably the main factor responsible for the variation in the adsorption of P on
aquatic sediments.
PMID- 28415027
TI - The influence of sex on mock jurors' verdicts across type of child abuse cases.
AB - This study examined the influence of victim sex, mock juror sex, and type of
child abuse (physical, sexual, emotional, and neglect) on mock jurors'
assessments of eyewitness and defendant integrity, continuous guilt ratings,
dichotomous verdicts, and sentencing recommendations. Participants read one of
eight versions of a trial transcript and then answered a self-report
questionnaire. Female mock jurors were significantly more likely to find the
defendant guilty overall. Moreover, female mock jurors recommended significantly
longer sentences for defendants in sexual abuse cases; whereas, male mock jurors
recommended significantly longer sentences for defendants in sexual and physical
abuse cases. Male mock jurors perceived the defendant more favorably than female
mock jurors; whereas, female mock jurors perceived the alleged victim more
favorable than male mock jurors. These results suggest that juror sex may be an
influential factor in child abuse cases overall.
PMID- 28415028
TI - The dynamics of multimer formation of the amphiphilic hydrophobin protein HFBII.
AB - Hydrophobins are surface-active proteins produced by filamentous fungi. They have
amphiphilic structures and form multimers in aqueous solution to shield their
hydrophobic regions. The proteins rearrange at interfaces and self-assemble into
films that can show a very high degree of structural order. Little is known on
dynamics of multimer interactions in solution and how this is affected by other
components. In this work we examine the multimer dynamics by stopped-flow
fluorescence measurements and Forster Resonance Energy Transfer (FRET) using the
class II hydrophobin HFBII. The half-life of exchange in the multimer state was
0.9s at 22 degrees C with an activation energy of 92kJ/mol. The multimer exchange
process of HFBII was shown to be significantly affected by the closely related
HFBI hydrophobin, lowering both activation energy and half-life for exchange.
Lower molecular weight surfactants interacted in very selective ways, but other
surface active proteins did not influence the rates of exchange. The results
indicate that the multimer formation is driven by specific molecular interactions
that distinguish different hydrophobins from each other.
PMID- 28415029
TI - Multifunctional nanoparticles self-assembled from polyethylenimine-based graft
polymers as efficient anticancer drug delivery.
AB - Multiple functionalization of nanoparticles has attracted great interest in drug
delivery. In this paper, polymeric amphiphiles of polyethylenimine (PEI)
conjugated with methoxy poly(ethylene glycol) aldehyde (mPEG-CHO), poly(epsilon
caprolactone) aldehyde (PCL-CHO) and pyrene-1-carboxaldehyde (Py-CHO) were
synthesized via Schiff's reaction. The conjugates self-assembled into
nanoparticles with pH-sensitivity to load anticancer drug doxorubicin (DOX),
further coated with hyaluronic acid (HA) for tumor targeting. The mean size of
nanoparticles was about 100nm and the stability of the nanoparticles was well in
aqueous solution. The nanoparticles coated with HA showed faster disassembly in
acidic solution, resulting in faster drug release in the medium with pH 5.0
compared to uncoated nanoparticles. Moreover, the nanoparticles exhibited an
endosomal escape function to accelerate the release of DOX in cancer cells, which
led to low IC50s to kill breast cancer cells (4T1) and liver cancer cells (HepG2)
in vitro.
PMID- 28415030
TI - Contradictory roles of Nrf2/Keap1 signaling pathway in cancer
prevention/promotion and chemoresistance.
AB - NF-E2-related factor 2 (Nrf2) protein is a cytosolic transcription factor that
regulates antioxidant and stress-related enzymes. Kelch-like ECH-associated
protein 1 (Keap1) binds Nrf2 and accelerates ubiquitination and proteasome
dependent degradation of Nrf2. Nrf2 modifies the sensitivity of the cell
environment to electrophiles and oxidants by inducing the transcriptional
activation of more than 100 detoxification and cytoprotective genes. Prior
investigations have found documentary evidence indicating that temporary
activation of Nrf2 by pharmaceutical inducers plays a protective role against
cancer initiation in normal cells. The impact of Nrf2/Keap1 pathway in
development of tumorigenesis and drug resistance has also been well documented.
Inhibition of the permanent Nrf2 activation, especially in combination with
chemotherapeutics against cancer, may be considered as an important strategy to
inhibit tumor growth and overcome chemoresistance. Here, we review the importance
of Nrf2-keap1 pathway in the prevention or promotion of cancer, and resistance
mechanisms to chemotherapeutic agents.
PMID- 28415031
TI - Carotenoid accumulation in durian (Durio zibethinus) fruit is affected by
ethylene via modulation of carotenoid pathway gene expression.
AB - Carotenoid content in durian (Durio zibethinus) fruit is an important aspect of
fruit quality, with different cultivars distinguished by differing pigmentation.
We have studied the dependence of carotenogenesis on ethylene. Fruit of the
cultivar 'Chanee' harvested at the mature stage were either left untreated
(controls), treated with 1-methylcyclopropene (1-MCP) for 12 h, or treated with
application of an aqueous ethephon solution to the stem end, or treated for 12 h
with 1-MCP followed by ethephon application. Fruit were then stored for 9 d at 25
degrees C. Pulp color of durian became steadily yellowish as a result of
accumulation of carotenoids, which were mainly beta-carotene, and alpha-carotene,
with a minor amount of zeaxanthin and lutein. 1-MCP delayed the increase in the
accumulation of beta-carotene, alpha-carotene, and zeaxanthin, but not lutein. In
contrast, ethephon had no significant effect on carotenoid accumulation. The
expression of zeta-carotene desaturase (ZDS), lycopene beta-cyclase (LCYB),
chromoplast specific lycopene beta-cyclase (CYCB) and beta-carotene hydroxylase
(BCH) genes was highly correlated with carotenoid content and pulp color.1-MCP
resulted in significant down-regulation of ZDS, LCYB, CYCB and BCH expression.
The accumulation of beta-carotene and alpha-carotene appears to be controlled by
the level of expression of LCYB gene, whose function was tested in bacteria to
show conversion of lycopene and delta-carotene to beta-carotene and alpha
carotene, respectively. These results suggest that ripening-induced carotenoid
accumulation is regulated by endogenous ethylene controlling the expression of
key genes such as LCYB.
PMID- 28415032
TI - Comparative metabolome analysis of wheat embryo and endosperm reveals the dynamic
changes of metabolites during seed germination.
AB - In this study, we performed the first comparative metabolomic analysis of the
wheat embryo and endosperm during seed germination using GC-MS/MS. In total, 82
metabolites were identified in the embryo and endosperm. Principal component
analysis (PCA), metabolite-metabolite correlation and hierarchical cluster
analysis (HCA) revealed distinct dynamic changes in metabolites between the
embryo and endosperm during seed germination. Generally, the metabolite changes
in the embryo were much greater than those in the endosperm, suggesting that the
embryo is more active than the endosperm during seed germination. Most amino
acids were upregulated in both embryo and endosperm, while polysaccharides and
organic acids associated with sugars were mainly downregulated in the embryo.
Most of the sugars showed an upregulated trend in the endosperm, but significant
changes in lipids occurred only in the embryo. Our results suggest that the
embryo mobilises mainly protein and lipid metabolism, while the endosperm
mobilises storage starch and minor protein metabolism during seed germination.
The primary energy was generated mainly in the embryo by glycolysis during seed
imbibition. The embryo containing most of the genetic information showed
increased nucleotides during seed germination process, indicating more active
transcription and translation metabolisms.
PMID- 28415033
TI - Physiological investigation of C4-phosphoenolpyruvate-carboxylase-introduced rice
line shows that sucrose metabolism is involved in the improved drought tolerance.
AB - We compared the drought tolerance of wild-type (WT) and transgenic rice plants
(PC) over-expressing the maize C4PEPC gene, which encodes phosphoenolpyruvate
carboxylase (PEPC, EC 4.1.1.31) gene, and evaluated the roles of saccharide and
sugar-related enzymes in the drought response. Pot-grown seedlings were subjected
to real drought conditions outdoors, and the yield components were compared
between PC and untransformed wild-type (WT) plants. The stable yield from PC
plants was associated with higher net photosynthetic rate under the real drought
treatment. The physiological characters of WT and PC seedlings under a simulated
drought treatment (25% (w/v) polyethylene glycol-6000 for 3 h; PEG 6000
treatment) were analyzed in detail for the early response of drought. The
relative water content was higher in PC than in WT, and PEPC activity and the C4
PEPC transcript level in PC were elevated under the simulated drought conditions.
The endogenous saccharide responses also differed between PC and WT under
simulated drought stress. The higher sugar decomposition rate in PC than in WT
under drought analog stress was related to the increased activities of sucrose
phosphate synthase, sucrose synthase, acid invertase, and neutral invertase,
increased transcript levels of VIN1, CIN1, NIN1, SUT2, SUT4, and SUT5, and
increased activities of superoxide dismutase and peroxidase in the leaves. The
greater antioxidant defense capacity of PC and its relationship with saccharide
metabolism was one of the reasons for the improved drought tolerance. In
conclusion, PEPC effectively alleviated oxidative damage and enhanced the drought
tolerance in rice plants, which were more related to the increase of the
endogenous saccharide decomposition. These findings show that components of C4
photosynthesis can be used to increase the yield of rice under drought
conditions.
PMID- 28415034
TI - Validation of a new mortality risk prediction model for people 65 years and older
in northwest Russia: The Crystal risk score.
AB - BACKGROUND: Prediction models help to make decisions about further management in
clinical practice. This study aims to develop a mortality risk score based on
previously identified risk predictors and to perform internal and external
validations. METHODS: In a population-based prospective cohort study of 611
community-dwelling individuals aged 65+ in St. Petersburg (Russia), all-cause
mortality risks over 2.5 years follow-up were determined based on the results
obtained from anthropometry, medical history, physical performance tests,
spirometry and laboratory tests. C-statistic, risk reclassification analysis,
integrated discrimination improvement analysis, decision curves analysis,
internal validation and external validation were performed. RESULTS: Older adults
were at higher risk for mortality [HR (95%CI)=4.54 (3.73-5.52)] when two or more
of the following components were present: poor physical performance, low muscle
mass, poor lung function, and anemia. If anemia was combined with high C-reactive
protein (CRP) and high B-type natriuretic peptide (BNP) was added the HR (95%CI)
was slightly higher (5.81 (4.73-7.14)) even after adjusting for age, sex and
comorbidities. Our models were validated in an external population of adults 80+.
The extended model had a better predictive capacity for cardiovascular mortality
[HR (95%CI)=5.05 (2.23-11.44)] compared to the baseline model [HR (95%CI)=2.17
(1.18-4.00)] in the external population. CONCLUSION: We developed and validated a
new risk prediction score that may be used to identify older adults at higher
risk for mortality in Russia. Additional studies need to determine which targeted
interventions improve the outcomes of these at-risk individuals.
PMID- 28415035
TI - Serum high-density lipoprotein cholesterol concentration and functional state:
The Korean Urban Rural Elderly (KURE) Study.
AB - BACKGROUND: Functional state and cholesterol metabolism are important for older
adults; however, this association has not been fully investigated among community
dwelling older adults. Thus, we investigated the association of HDL cholesterol
with multiple functional state measures in an elderly Korean population. METHODS:
This cross-sectional analysis included 3514 participants, aged 65 years or older,
who participated in baseline health assessment for the Korean Urban Rural Elderly
cohort study from 2012 to 2015. HDL cholesterol concentration was analyzed using
both continuous and categorical variables. Functional state was assessed by the
mini-mental state examination (MMSE), activities of daily living (ADL) scale,
instrumental activities of daily living (IADL) scale, timed up-and go (TUG) test,
and chair-rise test (CRT). Multiple logistic regression models were used to
investigate independent association between HDL cholesterol and functional state,
after adjusting for sex, age, body mass index, systolic blood pressure, fasting
glucose, lipid-lowering drug, history of cancer and cardiovascular disease, and
health behaviors. RESULTS: HDL cholesterol concentration was significantly
associated with MMSE, ADL, IADL, TUG, and CRT in the unadjusted model. After
adjustment for covariates, the association remained significant for MMSE
(standardized beta=0.059, p=0.001), ADL (standardized beta=-0.053, p=0.004), and
CRT (standardized beta=-0.037, p=0.037). In fully-adjusted model, Participants
who had a lower HDL concentration (<40mg/dL) showed significantly increased odds
for having MMSE decline (OR 1.451, 95% CI 1.119-1.883) and ADL dependency (OR
2.251, 95% CI 1.119-4.526), compared reference group (>=60mg/dL). CONCLUSIONS:
Higher HDL cholesterol concentration was associated with better functional state
among Korean older adults.
PMID- 28415036
TI - Toxic effects of glyphosate on diploid and triploid fin cell lines from Misgurnus
anguillicaudatus.
AB - We examined the toxic effects of glyphosate on diploid (DIMF) and triploid (TRMF)
fin cell lines from the Oriental Weather Loach Misgurnus anguillicaudatus. The
LC50 values of glyphosate estimated by methylthiazolyldiphenyl-tetrazolium
bromide (MTT) assay were 315.34 and 371.77 mg/L for DIMF and TRMF, respectively.
Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities in DIMF
and TRMF cells gradually increased and then decreased with increasing glyphosate
concentrations, reaching a maximum at 240 mg/L glyphosate. In contrast,
acetylcholinesterase (AChE) activities in DIMF and TRMF decreased with increasing
concentrations of glyphosate in a concentration-dependent manner. SOD and AChE
activities were generally significantly higher in TRMF compared with DIMF cells
(P < 0.05). The rates of micronucleus and abnormal nuclei were significantly
higher in DIMF and TRMF groups treated with 80-560 mg/L glyphosate compared with
the control groups (P < 0.01). The highest micronuclei rates in both DIMF and
TRMF cells (both 4.300/00) occurred at 400 mg/L glyphosate. There were no
differences in the rates of micronuclei and abnormal nuclei between DIMF and TRMF
cells at any glyphosate concentration. Cell damage, including chromatin
condensation, nucleus distortion, and broken and reduced endoplasmic reticulum,
mitochondria, and ribosomes, were found in both cells treated with the LC50
concentration of glyphosate. Moreover, vacuolization and apoptotic bodies
occurred in glyphosate-exposed DIMF and TRMF cells, indicating apoptosis. These
results indicate that glyphosate in the range of tested concentrations represent
a potential risk to loach through inhibiting proliferation of diploid and
triploid cell lines and induces micronuclei and apoptosis.
PMID- 28415037
TI - Enantiomer-specific accumulation and depuration of alpha-hexabromocyclododecane
(alpha-HBCDD) in chicken (Gallus gallus) as a tool to identify contamination
sources.
AB - A LC-ESI(-)-HRMS method dedicated to the analysis of 6 HBCDD enantiomers at trace
levels in animal matrices was developed, using a cellulose based stationary phase
with a particle size of 2.5 MUm. This method was applied to a sample set derived
from a kinetic study of alpha-HBCDD previously conducted in fast- and slow
growing chickens (Gallus gallus domesticus, n = 49, plus controls), in order to
study the enantiomer specific accumulation and depuration of alpha-HBCDD in
various tissues. Regarding abdominal adipose tissue, muscle and liver, the
average enantiomeric fractions of alpha-HBCDD (EFalpha) for continuously exposed
groups ranged between 0.434 and 0.467, with standard deviations below 0.014,
showing a significant enrichment in (-)alpha enantiomer even accentuated for slow
growing individuals during depuration with EFalpha reduced by about 0.020.
Similar trends were observed for pooled plasma. Then, EFalpha of circulating
plasma alpha-HBCDD appeared to closely reflect EFalpha in storage tissues and
liver, suggesting some equilibrium. The racemic elimination of alpha enantiomer
in excreta during the contamination phase indicated that no preferential
gastrointestinal absorption took place. By contrast, preferential excretion of (
)alpha-HBCDD from the circulating compartment to the intestinal lumen occurred
during the depuration. Finally, the method was applied to samples collected in
three chicken farms, selected for total HBCDD levels in muscle in the ng/g range,
as a tool to determine whether the contamination occurred ante- or post-mortem,
according to the chiral signature. Ante-mortem contamination was hypothesised for
2 farms, with feed being excluded as contamination source.
PMID- 28415038
TI - Adsorption of diclofenac onto goethite: Adsorption kinetics and effects of pH.
AB - The adsorption of diclofenac (DCF), one of the widely used non-steroidal anti
inflammatory drugs, onto the surface of goethite was investigated with batch
experiments. The adsorption at different pH values (5.3, 7.4, and 10.0) were well
fitted with the pseudo-second-order model. The results showed that the adsorption
of DCF onto goethite was strongly depended on solution pH. The amount of adsorbed
DCF decreased with increasing pH duo to electrostatic repulsive interactions.
Fourier transform infrared (FTIR) results indicated that carboxyl group (COOH)
might be involved in the adsorption, and DCF formed bidentate chelate and
bridging bidentate complexes on the surface of goethite.
PMID- 28415039
TI - Removal of fluoride, SDS, ammonia and turbidity from semiconductor wastewater by
combined electrocoagulation-electroflotation.
AB - Semiconductor industry effluents contain organic and inorganic pollutants, such
as sodium dodecyl sulfate (SDS), fluoride and ammonia, at high levels which
consists a major environmental issue. A combined EC-EF process is proposed as a
post-treatment after precipitation for simultaneous clarification and removal of
pollutants. In EC step, a hybrid Fe-Al was used as the soluble anode in order to
avoid supplementary EC step. EC-Fe is more suitable for SDS removal; EC-Al is
more suitable for fluoride removal, while EC with hybrid Al-Fe makes a good
compromise. Clarification and ammonia oxidation were achieved in the EF step.
Effects of anodic material, initial pH, current, anion nature, chloride
concentration and initial pollutant concentration were studied. The final
concentrations may reach 0.27, 6.23 and 0.22 mg L-1 for SDS, fluoride and ammonia
respectively. These concentrations are far lower than the correspondent discharge
limits. Similarly, the final turbidity was found 4.35 NTU which is lower than
5NTU and the treated water does not need further filtration before discharge.
Furthermore, the EC-EF process proves to be sufficiently energy-efficient with
less soluble electrode consumption.
PMID- 28415040
TI - Green fluorescent proteins induce oxidative stress in cells: A worrisome new
wrinkle in the application of the GFP reporter system to biological systems?
PMID- 28415041
TI - Environmental exposures to lead, mercury, and cadmium among South Korean
teenagers (KNHANES 2010-2013): Body burden and risk factors.
AB - INTRODUCTION: Limited information is available on the association of age and sex
with blood concentrations of heavy metals in teenagers. In addition, factors such
as a shared family environment may have an association. We analyzed data from the
Korean National Health and Nutrition Examination Survey (KNHANES, 2010-2013) to
determine whether blood levels of heavy metals differ by risk factors such as
age, sex, and shared family environment in a representative sample of teenagers.
METHODS: This study used data obtained in the KNHANES 2010-2013, which had a
rolling sampling design that involved a complex, stratified, multistage,
probability-cluster survey of a representative sample of the non
institutionalized civilian population in South Korea. Our cross-sectional
analysis was restricted to teenagers and their parents who completed the health
examination survey, and for whom blood measurements of cadmium, lead, and mercury
were available. The final analytical sample consisted of 1585 teenagers, and 376
fathers and 399 mothers who provided measurements of blood heavy metal
concentrations. RESULTS: Male teenagers had greater blood levels of lead and
mercury, but sex had no association with blood cadmium level. There were age
related increases in blood cadmium, but blood lead decreased with age, and age
had little association with blood mercury. The concentrations of cadmium and
mercury declined from 2010 to 2013. The blood concentrations of lead, cadmium,
and mercury in teenagers were positively associated with the levels in their
parents after adjustment for covariates. CONCLUSION: Our results show that blood
heavy metal concentrations differ by risk factors such as age, sex, and shared
family environment in teenagers.
PMID- 28415042
TI - Determinants of increasing serum POPs in a population at high risk for
cardiovascular disease. Results from the PREDIMED-CANARIAS study.
AB - Persistent organic pollutants (POPs) are well-known ubiquitous environmental
chemicals which have been related to adverse health outcomes, including
cardiovascular disease (CVD). The purpose of this study was to evaluate POPs
burden, and its determinants, in a population at high risk of suffering CVD
enrolled in the PREDIMED Study (Spanish acronym for PREvention by means of
MEDiterranean Diet). This cohort was formed by 343 participants (55-80 y.o.),
which were selected for a preventive nutritional intervention for CVD based on
the Mediterranean Diet. Relevant information on demographic, behavioral, dietary,
and socioeconomic characteristics was obtained from each participant through a
specific questionnaire, and their anthropometric and clinical measurements were
recorded. In addition, the levels of 35 POPs were determined in serum samples
taken before the beginning of the nutritional intervention. All the samples
showed detectable levels of, at least, one POP, being DDT-derivatives and marker
PCBs the most frequently detected compounds. Our results showed that people at
high risk for CVD showed a higher level of contamination by POPs as compared to
other studies done in cohorts of Western people at no special risk of CVD.
Although educational level seems to be a relevant determinant for POPs burden in
our population, the main determining factor seems to be the diet. Thus, while the
intake of food of animal origin was significantly associated with levels of PCBs,
especially in men, the intake of vegetal-origin food was positively related to
levels of organochlorine pesticides, indicating a different dietary source for
these two groups of chemicals. Our results showing that subjects at high risk for
cardiovascular disease present elevated POPs burden might have a relevant public
health impact given the generalized and difficult to avoid exposure to POPs and
the elevated worldwide frequency of the CVD.
PMID- 28415043
TI - Environmental stressors as a driver of the trait composition of benthic
macroinvertebrate assemblages in polluted Iberian rivers.
AB - We used the trait composition of macroinvertebrate communities to identify the
effects of pesticides and multiple stressors associated with urban land use at
different sites of four rivers in Spain. Several physical and chemical stressors
(high metal pollution, nutrients, elevated temperature and flow alterations)
affected the urban sites. The occurrence of multiple stressors influenced aquatic
assemblages at 50% of the sites. We hypothesized that the trait composition of
macroinvertebrate assemblages would reflect the strategies that the assemblages
used to cope with the respective environmental stressors. We used RLQ and fourth
corner analysis to address the relationship between stressors and the trait
composition of benthic macroinvertebrates. We found a statistically significant
relationship between the trait composition and the exposure of assemblages to
environmental stressors. The first RLQ dimension, which explained most of the
variability, clearly separated sites according to the stressors. Urban-related
stressors selected taxa that were mainly plurivoltine and fed on deposits. In
contrast, pesticide impacted sites selected taxa with high levels of egg
protection (better egg survival), indicating a potentially higher risk for egg
mortality. Moreover, the trait diversity of assemblages at urban sites was low
compared to that observed in pesticide impacted sites, suggesting the
homogenization of assemblages in urban areas.
PMID- 28415044
TI - Long non-coding RNA SNHG1 regulates zinc finger E-box binding homeobox 1
expression by interacting with TAp63 and promotes cell metastasis and invasion in
Lung squamous cell carcinoma.
AB - The long non-coding RNAs (lncRNAs) have been recently shown to participate in the
progression of a variety of cancers. However, the biological role of lncRNAs and
the underlying mechanisms in Lung squamous cell carcinoma (SCC) or lung
adenocarcinoma (AD) remain unclear. Herein, we investigated expression of 5
lncRNAS (SNHG1, NCBP2-AS2, LINC01206, SOX2-OT and LINC01419) in SCC and AD
tissues. SNHG1 was one of over-expressed lncRNAs in SCC tissues. Knockdown of
SNHG1 significantly inhibited the proliferation, metastasis, invasive ability and
induced apoptosis of SCC cells. Moreover, SNHG1 affected the expression of zinc
finger E-box binding homeobox 1(ZEB1), which has also been observed to be up
regulated in SCC and to promote cell metastasis and invasion. Rather than direct
interaction, SNHG1 regulated ZEB1expression by suppressing the activity of p63 TA
isoform (TAp63), which is a repressor of ZEB1 and physically associates with
SNHG1. Furthermore, SNHG1 promoted ZEB1 expression and promoted cell
proliferation, metastasis, invasive but inhibited apoptosis of SCC cells via the
TAp63/ZEB1 pathway. Taken together, our findings suggested that SNHG1 might play
an oncogenic role in SCC through ZEB1 signaling pathway by inhibiting TAp63 and
might serve as a valuable prognostic biomarker and therapeutic target for SCC
patients.
PMID- 28415045
TI - Knockdown of PEBP4 suppresses proliferation, migration and invasion of human
breast cancer cells.
AB - Phosphatidylethanolamine-binding protein 4 (PEBP4), a member of the PEBP family,
plays a pivotal role in tumor progression. However, the roles of PEBP4 in breast
cancer remain unclear. Therefore, in the present study, we investigated the
effects of PEBP4 on breast cancer cell proliferation, migration and invasion, and
the underlying mechanism was also explored. Our results showed that the
expression of PEBP4 was significantly up-regulated in breast cancer cell lines.
Knockdown of PEBP4 inhibited breast cancer cell proliferation in vitro and tumor
growth in vivo. Furthermore, knockdown of PEBP4 suppressed breast cancer cell
migration and invasion with prevented EMT. Mechanistically, knockdown of PEBP4
inhibited breast cancer cell proliferation and migration through the inactivation
of PI3K/Akt signaling pathway. In conclusion, the present study demonstrated for
the first time that knockdown of PEBP4 inhibited the proliferation, invasion and
tumorigenesis in breast cancer cells. Thus, PEBP4 may serve as a potential
therapeutic target for the treatment of breast cancer.
PMID- 28415047
TI - PLOD2 in cancer research.
AB - Collagen is not only the most abundant protein providing the scaffold for
assembly of the extracellular matrix (ECM), but also considered to be the
"highway" for cancer cell migration and invasion depending on the different
collagen organizations. The accumulation of stabilized collagen is enhanced by
different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the
PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen
cross-link. Interestingly, PLOD2 is overexpressed in different cancers and
closely related to a poor prognosis. To the best of our knowledge, only the
mechanisms of PLOD2 regulated by HIF-1alpha, TGF-beta and microRNA-26a/b have
been elaborated. In addition, several pharmacologic inhibitors of PLOD2 have been
confirmed to have an anti-metastasis effect. However, there have been no reviews
about PLOD2 in cancer research published thus far. In brief, this review about
PLOD2 will describe the function, regulatory mechanism, and the inhibitors of
PLOD2 in cancer, suggesting the credible clinical evaluation of a prognostic
signature in pathological examination and the possible development of therapeutic
strategies targeting PLOD2 in the future.
PMID- 28415046
TI - Cost-benefit effectiveness of angiotensin-II receptor blockers in patients with
uncomplicated hypertension: A comparative analysis.
AB - OBJECTIVE: The treatment of hypertensive patients (HTs) requires a long-term
commitment of compliance for the patient and resources by the healthcare system.
This poses an economic dilemma in countries where universal healthcare is
standard. The aim of this study was to evaluate the costs/health benefit and
effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in
uncomplicated essential hypertension. DESIGN AND METHODS: The daily and annual
economic commitment for treating patients with ARBs was estimated using pharmacy
dispensing records and the BP-lowering effects of candesartan, irbesartan,
losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively. In
114 HTs (mean age 59.4+/-13.5year, 57.5% men), the BP-lowering effect of ARBs as
in monotherapy and in fixed-dose combination (FDC) with hydrochlorothiazide at
the doses commonly used in the market to reach BP control (i.e. BP <140/90mmHg)
was analyzed. The BP lowering-effect was evaluated after an average of 6-month
follow-up consulting medical professionals. Analysis of variance for repeated
measures was provided. RESULTS: Treatment with candesartan (14.1%) and olmesartan
(32,4%) versus other ARBs resulted in a significant decrease in BP as for mono-
than for FDC therapy. Our studies suggest that daily (data not shown) and annual
costs of olmesartan were higher than candesartan as in mono- (4577.71+/-1120.55
vs. 894.25+/-127.75 ?) than for FDC therapy (5715.90+/-459.90 vs. 1580.45+/
113.15 ?). CONCLUSIONS: Treatment: of BP with candesartan appears to be the most
favorable option in terms of cost-effectiveness coupled with favorable health
outcomes. These data have some limitations, but open the question if candesartan
should be preferred to olmesartan in BP management. Further prospective studies
comparing ARBs based on their effect on BP control in uncomplicated HTs are
needed for validation.
PMID- 28415048
TI - Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via
PI3K/Akt/NF-kappaB pathway.
AB - Baicalein, a bioactive flavonoid, exhibits anti-inflammatory and anti-cancer
activities. However, few studies reported the interaction of baicalein with
chemotherapeutic agents. Our study showed that baicalein significantly enhanced
the chemosensitivity of cisplatin (CDDP) in vivo and in vitro. We found that
A549/CDDP (resistant to CDDP) cells not only acquired epithelial-mesenchymal
transition (EMT) phenotype, but also showed increased NF-kappaB activity compared
with A549 cells (sensitive to CDDP). Our study further demonstrated that
PI3K/Akt/NF-kappaB pathway controlled CDDP resistance via EMT and NF-kappaB
mediated apoptosis. Baicalein significantly suppressed the PI3K/Akt/NF-kappaB
pathway, leading to conversion of EMT to mesenchymal-epithelial transition (MET,
the reciprocal mesenchymal to epithelial transition), and inhibition of NF-kappaB
mediated antiapoptotic proteins in A549/CDDP cells. In conclusion, our study
demonstrated that baicalein reversed the resistance of human A549 lung
adenocarcinoma cells to cisplatin by inhibiting EMT and attenuating apoptosis via
PI3K/Akt/NF-kappaB pathway.
PMID- 28415049
TI - Metamorphosis and transition between developmental stages in European eel
(Anguilla anguilla, L.) involve epigenetic changes in DNA methylation patterns.
AB - The life history of the European eel (Anguilla anguilla, L.) is characterized by
a series of metamorphoses and transitions that provoke drastic morphological
changes. Most of these changes go along with the catadromous life cycle in eels,
involving extensive physiologically adaptations. In this study it was
investigated whether these drastic changes have an epigenetic basis by analyzing
global methylation patterns in liver, gill and brain tissue from glass eels
caught at the British coast as well as yellow and silver eels from River Rhine
using methylation-sensitive amplified polymorphisms (MSAP). Analysis of molecular
variance (AMOVA) on MSAP data derived from liver tissue revealed only minor
differences in methylation patterns between glass, yellow and silver eels,
reflecting uniform functioning of the liver throughout the investigated lifespan.
In brain and gill tissue, however, marked differences in methylation patterns
were found. Principal coordinates analysis (PCoA) revealed yellow eels being
partially clustered with silver eels and a more distinct cluster of glass eels
based on the methylation patterns in the brain. According to results found in the
gills, glass eels were more similar to silver eels whereas yellow eels were found
to be clustered separately. From these results it can be concluded that
epigenetic changes in gill tissue most likely reflect and are linked with
adaptation towards salt- and freshwater conditions. The observed differences in
brain methylation patterns, however, might be linked to morphological and
physiological changes during metamorphosis and transitions within the life
history of European eels potentially affecting subsequent differential gene
expression patterns required for such changes.
PMID- 28415050
TI - Free radicals and polyphenols: The redox chemistry of neurodegenerative diseases.
AB - The oxidation of bioorganic materials by air and, particularly, the oxidative
stress involved in the cell loss and other pathologies associated with
neurodegenerative diseases (NDs) are of enormous social and economic importance.
NDs generally involve free radical reactions, beginning with the formation of an
initiating radical by some redox, thermal or photochemical process, causing
nucleic acid, protein and lipid oxidations and the production of harmful
oxidative products. Physically, persons afflicted by NDs suffer progressive loss
of memory and thinking ability, mood swings, personality changes, and loss of
independence. Therefore, the development of antioxidant strategies to retard or
minimize the oxidative degradation of bioorganic materials has been, and still
is, of paramount importance. While we are aware of the importance of
investigating the biological and medical aspects of the diseases, elucidation of
the associated chemistry is crucial to understanding their progression, heading
to intelligent chemical intervention to find more efficient therapies to prevent
or delay the onset of the diseases. Accordingly, this review aims to provide the
reader with a chemical base to understand the behavior and properties of the
reactive oxygen species involved and of typical radical scavengers such as
polyphenolic antioxidants. Some discussion on the structures of the various
species, their formation, chemical reactivities and lifetimes is included. The
ultimate goal is to understand how, when and where they form, how far they travel
prior to react, which molecules are their targets, and how we can, eventually,
control their activity to minimize their impact by means of chemical methods.
Recent strategies explore chemical modifications of the hydrophobicity of potent,
natural antioxidants to improve their efficiency by fine-tuning their
concentrations at the reaction site.
PMID- 28415051
TI - Cross-interference of two model peroxisome proliferators in peroxisomal and
estrogenic pathways in brown trout hepatocytes.
AB - Peroxisome proliferators cause species-specific effects, which seem to be
primarily transduced by peroxisome proliferator-activated receptor alpha
(PPARalpha). Interestingly, PPARalpha has a close interrelationship with
estrogenic signaling, and this latter has already been promptly activated in
brown trout primary hepatocytes. Thus, and further exploring this model, we
assess here the reactivity of two PPARalpha agonists in direct peroxisomal routes
and, in parallel the cross-interferences in estrogen receptor (ER) mediated
paths. To achieve these goals, three independent in vitro studies were performed
using single exposures to clofibrate - CLF (50, 500 and 1000MUM), Wy-14,643 - Wy
(50 and 150MUM), GW6471 - GW (1 and 10MUM), and mixtures, including PPARalpha
agonist or antagonist plus an ER agonist or antagonist. Endpoints included gene
expression analysis of peroxisome/lipidic related genes (encoding apolipoprotein
AI - ApoAI, fatty acid binding protein 1 - Fabp1, catalase - Cat, 17 beta
hydroxysteroid dehydrogenase 4 - 17beta-HSD4, peroxin 11 alpha - Pex11alpha,
PPARalphaBb, PPARalphaBa and urate oxidase - Uox) and those encoding estrogenic
targets (ERalpha, ERbeta-1 and vitellogenin A - VtgA). A quantitative
morphological approach by using a pre-validated catalase immunofluorescence
technique allowed checking possible changes in peroxisomes. Our results show a
low responsiveness of trout hepatocytes to model PPARalpha agonists in direct
target receptor pathways. Additionally, we unveiled interferences in estrogenic
signaling caused by Wy, leading to an up-regulation VtgA and ERalpha at 150MUM;
these effects seem counteracted with a co-exposure to an ER antagonist. The
present data stress the potential of this in vitro model for further exploring
the physiological/toxicological implications related with this nuclear receptor
cross-regulation.
PMID- 28415053
TI - [Treatment Types and Optimal Age for Craniosynostosis].
PMID- 28415052
TI - Viral gene products actively promote latent infection by epigenetic silencing
mechanisms.
AB - Many viruses undergo an acute infection in the host organism and then are cleared
by the ensuing host immune response, but other viruses establish a persistent
infection involving a latent infection or a chronic infection. Latent infection
by the herpesviruses or human immunodeficiency virus involves epigenetic
silencing of the DNA genome or proviral genome, respectively. Latent infection
was previously thought to be a default pathway resulting from infection of a
nonpermissive cell, but recent studies have shown that viral gene products can
promote epigenetic silencing and latent infection. This review will summarize the
viral gene products that have been shown to promote epigenetic silencing of the
genomes and their potential for therapeutics to target these viral gene products
and disrupt or lock in latent infection.
PMID- 28415054
TI - [Hemodialysis Increases the Incidence of Post-Traumatic Seizure in Hemodialysis
Patients with Traumatic Intracranial Hemorrhage].
AB - BACKGROUND: In Japan, the number of hemodialysis patients increases every year,
along with the average age of this patient population. Further, certain
complications of hemodialysis make the care of traumatic head injury(THI)patients
particularly difficult. OBJECTIVE: This study was aimed at investigating the
occurrence of and risk factors for post-traumatic seizures in hemodialysis
patients with a history of THI, and determining patient outcomes. METHODS:
Subjects were selected from patients who were admitted to Yaizu Municipal
Hospital in Shizuoka, Japan for traumatic intracranial hemorrhage(TICH).
Retrospective medical histories of TICH patients who were and were not receiving
hemodialysis were reviewed to investigate the risk factors for seizures and to
determine patient outcomes. RESULTS: We identified 18 THI patients on
hemodialysis and 86 THI patients not on hemodialysis treatment. We determined
that predictive factors of post-traumatic seizure include:current hemodialysis
treatment, enlargement of an existing hematoma, and an acute subdural hematoma.
Moreover, 66.7% of seizures in our dialysis patients occurred during
hemodialysis. Our data also suggest that Glasgow Coma Scale(GCS)scores on
admission are a predictive factor for patient outcomes following discharge.
CONCLUSION: Current hemodialysis treatment, enlargement of an existing hematoma,
and an acute subdural hematoma are predictive factors of seizure occurrence in
THI patients. As post-traumatic seizures triggered unfavorable outcomes in some
dialysis patients, it is important to create appropriate plans for preventing
dialysis disequilibrium syndrome that may lead to seizures in TICH/TIH patients
on hemodialysis. We also determined that a low GCS score upon admission is a
significant predictor of unfavorable outcomes.
PMID- 28415055
TI - [Risk Factors for Predicting the Need for Additional Surgery for Symptomatic
Adjacent Segment Disease after Minimally Invasive Surgery-Transforaminal Lumbar
Interbody Fusion].
AB - PURPOSE: To determine the incidence of and risk factors for symptomatic adjacent
segment disease(SASD)requiring additional surgery in patients previously treated
with minimally invasive surgery-transforaminal lumbar interbody fusion(MIS
TLIF)for degenerative lumbar disease. MATERIALS AND METHODS: A series of 467
consecutive patients who had undergone MIS-TLIF of one or two segments to treat
degenerative lumbar disease was identified. The mean age of the patients at the
time of the index operation was 67.7 years and the mean follow-up period was 33.2
months(range, 6.0-110.1 months). The incidence rate of SASD surgeries was
calculated using the Kaplan-Meier method. The log-rank test and Cox regression
analysis were used for risk factor analysis based on age, sex, number of fused
segments, presence of laminectomy adjacent to index fusion, and L1 plumb line.
RESULTS: The overall incidence rate of SASD requiring additional surgery was
2.8%. Kaplan-Meier analysis predicted a disease-free rate of adjacent segments in
94.3% of the patients at 4 years and in 90.8% of the patients at 8 years after
the index operation. In the analysis of risk factors, a negative L1 plumb line
was associated with a 5.6 times higher incidence of SASD requiring additional
surgery than that associated with a positive L1 plumb line(p=0.0096). There was
no significant difference in the survival rates based on age, sex, number of
fused segments, and concomitant laminectomy to adjacent segment. CONCLUSION:
Approximately 9.2% of the patients were predicted to undergo additional surgery
for treating SASD within 8 years of MIS-TLIF. In this study, presence of a
negative L1 plumb line indicated higher incidence of additional SASD associated
surgeries than that shown by a positive L1 plumb line. Therefore, surgeons should
carefully consider this factor while performing MIS-TLIF.
PMID- 28415056
TI - [Pulsatile Tinnitus due to an Aberrant Internal Carotid Artery in the Middle
Ear:A Case Report].
AB - We report a rare case of aberrant internal carotid artery in the middle ear. The
patient was a 30-year-old man with pulsatile tinnitus. MRA and 3D-CTA revealed an
aberrant course of the internal carotid artery in the middle ear. 3D-CTA proved
useful for radiographic diagnosis, leading to the observation of an aberrant
internal carotid artery passing the foramen. We discuss the diagnosis and
management of such patients.
PMID- 28415057
TI - [De Novo Cavernous Angioma Secondary to a Developmental Venous Anomaly:A Case
Report and Review of the Literature].
AB - OBJECTIVE: Previously, cavernous angiomas(CAs)have been thought to be only
congenital in origin. Recently, however, a few cases of de novo CAs have been
reported in the literature. We present a case of a de novo CA and discuss the
etiology of the newly appeared CA. CASE REPORT: A 29-year-old man was presented
to a local clinic because of hypersomnia. MRI demonstrated a heterogeneous mass
peripherally located, which was in contact with a developmental venous
anomaly(DVA)at the left thalamus. Six years before the presentation, he visited
the same clinic because of faintness, and MRI results indicated no abnormality
except for the DVA. Three weeks later, he suddenly experienced difficulty in
speech, and the MRI revealed an increase in the size of the mass. Subsequently,
he was admitted at our institution, and neurological examination revealed aphasia
and right hemiparesis. A left carotid angiogram on venous phase showed a
narrowing of the DVA, which was seen as it entered the internal cerebral vein.
The diagnosis of a de novo CA was made. The mass was completely resected through
the transcallosal transventricular approach to avoid injuring the DVA. The DVA
could not be found during surgery. The pathological diagnosis was in line with
the findings of CA. Postoperatively, the patient continued having difficulty in
speech and was transferred to another institution for speech rehabilitation.
CONCLUSIONS: Although the association of CA and DVA has been described with
increasing frequencies recently, the etiology of de novo CA in the case of this
association has been a matter of debate. In the present case, it was speculated
that a narrowing of the DVA resulted in increased venous pressure and caused the
development of de novo CA.
PMID- 28415058
TI - [A Case of Arteriovenous Malformation of the Parotid Gland Associated with Cowden
Disease].
AB - We report a rare case of arteriovenous malformation(AVM)of the parotid gland
associated with Cowden disease successfully treated with preoperative
embolization followed by surgical removal. A 39-year-old man with a history of
Cowden disease presented with a pulsating and growing mass on his left lower jaw.
Contrast-enhanced computed tomography(CT)and angiography revealed a high-flow AVM
in the deep lobe of the left parotid gland. After intravascular embolization of
the feeding arteries, surgery was performed using the NIM
response(r)3.0, facial nerve monitoring system. The AVM was almost
completely removed and the facial nerves were morphologically preserved.
Interestingly, the intraoperative findings revealed that the enlarged vasa
nervorum of the facial nerve also fed the AVM. Although left facial nerve palsy
appeared after the surgery, the nerve function gradually improved over one year.
No recurrence of the AVM has been observed for one year.
PMID- 28415059
TI - [A Case of Slowly Progressive Brain Metastasis with Minor Bleeding after Removal
of and Chemotherapy for Non-Small Cell Lung Cancer].
AB - Of all brain metastases, the most common primary lesion is derived from the lung.
These types of metastases enlarge aggressively with unfavorable prognoses. We
report the case of a 75-year-old male patient who had a history of pulmonary
resection for Stage IA non-small cell lung cancer(NSCLC), and received
chemotherapy. One year after NSCLC surgery, he experienced a cardiogenic cerebral
infarction, and anticoagulant therapy was initiated. Mass lesions with hemorrhage
were detected bilaterally in the frontal lobes through magnetic resonance imaging
three years after the NSCLC surgery. The lesions slowly enlarged during follow
up. However, there were no clinical symptoms. There was no finding indicating a
local recurrence or metastasis through positron emission tomography(PET). Two and
a half years after the detection of the lesion, left hemiplegia was observed.
Massive hemorrhage from the right frontal lobe lesion was observed on computed
tomography(CT). Craniotomy and evacuation of the hematoma were performed. The
histopathological findings showed adenocarcinoma and the diagnosis was brain
metastasis of the lung cancer. This case reveals brain metastasis of lung cancer
that progressed without extracranial metastases for three years. The brain tumor
enlarged, accompanied by hemorrhage, extremely slowly without any symptoms. It
was difficult to differentiate between metastasis and cavernous hemangioma,
considering the extremely slow progress and image analyses. Of the reported
prognostic factors associated with postoperative brain metastasis from surgically
resected NSCLC, three factors were applicable to this case:adenocarcinoma, a
small number of brain metastases, and the absence of extracranial metastases at
the diagnosis of brain metastasis. We should consider the possibility of a
metastatic brain tumor secondary to lung cancer even long after thoracic surgery.
PMID- 28415060
TI - [A Case of Foramen Magnum Meningioma Manifesting as Hypoglossal Nerve Palsy].
AB - We report a case of foramen magnum meningioma manifesting as hypoglossal nerve
palsy. A 72-year-old woman presented with progressive hypoglossal nerve palsy and
lingual atrophy on the left side. Gadolinium-enhanced T1-weighted magnetic
resonance imaging revealed a heterogeneously enhanced mass lesion with dural tail
sign partially extending into the hypoglossal canal. The transcondylar approach
was performed to expose the hypoglossal canal and resect the tumor completely.
Histological examination revealed a transitional meningioma. The postoperative
course was uneventful. Hypoglossal nerve palsy improved gradually after the
operation.
PMID- 28415061
TI - [A Case of Subarachnoid Hemorrhage with Multiple Cerebral Aneurysms with a
Difficult-to-Identify Rupture Site].
PMID- 28415062
TI - [Pre- and Intra-Operative Supporting Technology for Brain
Tumors(6)Cerebellomedullary Fissure Approach for Fourth Ventricle Tumors].
PMID- 28415064
TI - Physical Demands of Multimodal Training Competitions and Their Relationship to
Measures of Performance.
AB - Jagim, AR, Rader, O, Jones, MT, and Oliver, JM. Physical demands of multimodal
training competitions and their relationship to measures of performance. J
Strength Cond Res 31(5): 1212-1220, 2017-The purpose of this study was to
identify the physical demands of multimodal training (MMT) competitions and to
determine the extent of their relationship to select measures of performance.
Eighteen (>1.5 years of strength training experience) men (n = 10) and women (n =
8) (mean +/- SD; age: 37.8 +/- 10.6 years, height: 172.8 +/- 8 cm, weight: 77.4
+/- 13.2 kg, 16.6 +/- 6% body fat) with experience performing MMT participated in
a simulated MMT competition. All participants were assessed for body composition,
countermovement vertical jump, and aerobic capacity during baseline testing. All
participants then participated in a simulated MMT-style competition on a separate
day within 10 days of baseline testing. The simulated MMT-style competition
consisted of 3 events with 90 minutes of recovery allowed in between events.
During the events, changes in blood lactate (La), heart rate (HR), and estimated
V[Combining Dot Above]O2 were recorded. Bivariate (Pearson) correlations were
computed to determine if a relationship existed between traditional measures of
performance and those of the MMT-style competition. Significance was set at p <=
0.05. Mean change in La ranged between 9 and 12 mmol.L during the events. Mean HR
and estimated V[Combining Dot Above]O2 values ranged from 145 to 172 b.min and 24
to 35 ml.kg.min, respectively, during the events. A strong correlation was
observed (r = -0.722; p < 0.001) between aerobic capacity and time to completion
for event 1. There was a strong correlation between lean body mass and lower-body
strength performance (r = 0.882; p < 0.001) and time to completion for event 3 (r
= -0.792; p < 0.001). A strong correlation was observed between lower-body power
and time to completion for event 1 (r = -0.755; p < 0.001) and event 3 (r =
0.818; p < 0.001). Based on the results of this study, MMT-style competitions
appear to be physically demanding activities performed at a high intensity with a
great involvement of the anaerobic energy system and that some measures of
aerobic capacity and power correlate with performance. When training for MMT
style competitions, it may be beneficial to focus on improving lower-body power
and/or aerobic capacity.
PMID- 28415063
TI - Neuron-restrictive silencer factor-mediated downregulation of MU-opioid receptor
contributes to the reduced morphine analgesia in bone cancer pain.
AB - Bone cancer pain has been reported to have unique mechanisms and is resistant to
morphine treatment. Recent studies have indicated that neuron-restrictive
silencer factor (NRSF) plays a crucial role in modulating the expression of the
MU-opioid receptor (MOR) gene. The present study elucidates the regulatory
mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma
inoculated murine model, pain behaviors that represent continuous or breakthrough
pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and
spinal dorsal horn was quantified at the transcriptional and translational
levels, respectively. Additionally, chromatin immunoprecipitation assays were
used to detect NRSF binding to the promoter of MOR. Furthermore, NRSF was
genetically knocked out by antisense oligodeoxynucleotide, and the expression of
MOR and the effect of morphine were subsequently analyzed. Our results indicated
that in a sarcoma murine model, NRSF expression is upregulated in dorsal root
ganglion neurons, and the expression of NRSF mRNA is significantly negatively
correlated with MOR mRNA expression. Additionally, chromatin immunoprecipitation
analysis revealed that NRSF binding to the neuron-restrictive silencer element
within the promoter area of the MOR gene is promoted with a hypoacetylation state
of histone H3 and H4. Furthermore, genetically knocking down NRSF with antisense
oligodeoxynucleotide rescued the expression of MOR and potentiated the systemic
morphine analgesia. The present results suggest that in sarcoma-induced bone
cancer pain, NRSF-induced downregulation of MOR is involved in the reduction of
morphine analgesia. Epigenetically, up-regulation of MOR could substantially
improve the effect of system delivery of morphine.
PMID- 28415065
TI - Acute Effect of Biomechanical Muscle Stimulation on the Counter-Movement Vertical
Jump Power and Velocity in Division I Football Players.
AB - Jacobson, BH, Monaghan, TP, Sellers, JH, Conchola, EC, Pope, ZK, and Glass, RG.
Acute effect of biomechanical muscle stimulation on the counter-movement vertical
jump power and velocity in division I football players. J Strength Cond Res
31(5): 1259-1264, 2017-Research regarding whole body vibration (WBV) largely
supports such training augmentation in attempts to increase muscle strength and
power. However, localized biomechanical vibration has not received the same
attention. The purpose of this study was to assess peak and average power before
and after acute vibration of selected lower-body sites in division I athletes.
Twenty-one subjects were randomly assigned to 1 of 2 conditions using a cross
over design. Pretest consisted of a counter-movement vertical jump (VJ) followed
by either localized vibration (30 Hz) to 4 selected lower-body areas or 4 minutes
of moderately low-resistance stationary cycling (70 rpm). Vibration consisted of
1 minute bouts at each lower-leg site for a total of 4 minutes followed by an
immediate post-test VJ. Repeated measures analysis of variance yielded no
significant differences (p > 0.05) in either peak power or peak velocity.
Similarly, no significant differences were found for average power and velocity
between conditions. It should be noted that, while not significant, the vibration
condition demonstrated an increase in peak power and velocity while the bike
condition registered slight decreases. Comparing each of the post-VJ repetitions
(1, 2, and 3) the vibration condition experienced significantly greater peak
power and velocity from VJ 1 to VJ 3 compared with the bike condition which
demonstrated no significant differences among the post-test VJs. These results
yielded similar, although not statistically significant outcomes to previous
studies using WBV. However, the novelty of selected site biomechanical vibration
merits further investigation with respect to frequency, magnitude, and duration
of vibration.
PMID- 28415066
TI - Effect of Barbell Weight on the Structure of the Flat Bench Press.
AB - Krol, H and Golas, A. Effect of barbell weight on the structure of the flat bench
press. J Strength Cond Res 31(5): 1321-1337, 2017-In this study, we have used the
multimodular measuring system SMART. The system consisted of 6 infrared cameras
and a wireless module to measure muscle bioelectric activity. In addition, the
path of the barbell was measured with a special device called the pantograph. Our
study concerns the change in the structure of the flat bench press when the
weight of the barbell is increased. The research on the bench press technique
included both the causes of the motion: the internal structure of the movement
and the external kinematic structure showing the effects of the motion, i.e., all
the characteristics of the movement. Twenty healthy, male recreational weight
trainers with at least 1 year of lifting experience (the mean +/- SD = 3.3 +/-
1.6 years) were recruited for this study. The subjects had a mean body mass of
80.2 +/- 8.6 kg, an average height of 1.77 +/- 0.08 m, and their average age was
24.7 +/- 0.9 years. In the measuring session, the participants performed
consecutive sets of a single repetition of bench pressing with an increasing load
(about 70, 80, 90, and 100% of their 1 repetition maximum [1RM]). The results
showed a significant change in the phase structure of the bench press, as the
barbell weight was increased. While doing the bench press at a 100% 1RM load, the
pectoralis major changes from being the prime mover to being the supportive prime
mover. At the same time, the role of the prime mover is taken on by the
deltoideus anterior. The triceps brachii, in particular, clearly shows a greater
involvement.
PMID- 28415067
TI - Effect of Whey Protein in Conjunction With a Caloric-Restricted Diet and
Resistance Training.
AB - Dudgeon, WD, Kelley, EP, and Scheett, TP. Effect of whey protein in conjunction
with a caloric-restricted diet and resistance training. J Strength Cond Res
31(5): 1353-1361, 2017-Caloric-restricted weight loss, especially rapid weight
loss, results from a decrease in both lean and fat mass (FM). The goal for many
is to lose FM while retaining lean body mass (LBM) and muscular performance thus
many turn to supplements. Sixteen resistance-trained men (24 +/- 1.6 years of
age) completed a 4 d.wk body building style split resistance training program for
8 weeks in conjunction with a pre-exercise, periexercise, and postexercise
ingestion of whey protein (WHEY) nutritional supplement or carbohydrate (CON)
based nutritional supplement. There were no differences in body mass change
between the WHEY and CON groups although both groups lost body mass (p <= 0.05);
however, WHEY group maintained LBM whereas the CON group lost (p <= 0.05), and
the WHEY group lost FM (p > 0.05) and the CON group did not, although the change
in FM between groups was not different. Both the WHEY and CON (p <= 0.05) groups
significantly increased lower-body strength. The WHEY group increased upper-body
strength (p <= 0.05), whereas the CON did not change. Both groups (p <= 0.05)
increased lower-body repetitions to fatigue with the increase greater in the CON
group (p <= 0.05). The CON group also increased upper-body repetitions (p <=
0.05) whereas WHEY did not. WHEY group lost body mass, composed of FM, whereas
CON also experienced a loss in body mass, but this loss was due to decrease in
LBM. Neither group experienced a loss in muscle performance, with the WHEY group
tending to show improvement in strength and CON group in endurance. These data
indicate WHEY supplementation compared with carbohydrate supplementation, during
a caloric-restricted "cut" diet can assist in maintaining LBM while allowing for
the loss of FM.
PMID- 28415068
TI - Validity and Reliability of a Portable Isometric Mid-Thigh Clean Pull.
AB - James, LP, Roberts, LA, Haff, GG, Kelly, VG, and Beckman, EM. Validity and
reliability of a portable isometric mid-thigh clean pull. J Strength Cond Res
31(5): 1378-1386, 2017-This study investigated the test-retest reliability and
criterion validity of force-time curve variables collected through a portable
isometric mid-thigh clean pull (IMTP) device equipped with a single-axial load
cell. Fifteen males with >=6 months of resistance training experience attended
two testing sessions. In each session, participants performed an IMTP in 2
separate conditions in a randomized counterbalanced manner. The criterion
condition consisted of a closed-chain IMTP configured with a force plate (IMTPf),
whereas the experimental test was undertaken using a portable IMTP with data
acquired through a single-axial load cell (IMTPl). A very high reliability
(coefficient of variation [CV] = 3.10, 90% confidence interval [CI]: 2.4-4.6%;
intraclass correlation coefficient [ICC] = 0.96, 90% CI: 0.90-0.98) and
acceptable validity (CV = 9.2, 90% CI: 7-14%; ICC = 0.88, 90% CI: 0.71-0.95) were
found in the experimental condition for the measure of peak force. However,
significant differences were present between the IMTPf and IMTPl (p < 0.0001).
Alternate force-time curve variables did not reach acceptable levels of validity
or reliability in the experimental condition. The IMTPl is a valid and highly
reliable method for assessing peak force. This provides evidence supporting the
use of an IMTPl as a cost-effective and portable alternative for those who wish
to assess maximal force production in a similar fashion to a traditional IMTP.
However, practitioners should be aware that these are slightly different tests.
PMID- 28415070
TI - Game Times and Higher Winning Percentages of West Coast Teams of the National
Football League Correspond With Reduced Prevalence of Regular Season Injury:
Erratum.
PMID- 28415069
TI - Comparison of Bioimpedance and Underwater Weighing Body Fat Percentage Before and
Acutely After Exercise at Varying Intensities.
AB - Nickerson, BS, Esco, MR, Kliszczewicz, BM, and Freeborn, TJ. Comparison of
bioimpedance and underwater weighing body fat percentage before and acutely after
exercise at varying intensities. J Strength Cond Res 31(5): 1395-1402, 2017-The
purpose of this study was to compare single-frequency bioelectrical impedance
analysis (BIA) and bioimpedance spectroscopy (BIS) with underwater weighing (UWW)
body fat percentage (BF%) before (PRE), immediately post (IP), and 60 minutes
post (60P) an acute bout of moderate and vigorous aerobic exercise. Nine men (age
= 24.6 +/- 3.7 years) volunteered for this study. Subjects visited the laboratory
on 3 separate occasions. Testing included two 30-minute exercise sessions at 60
and 80% heart rate reserve (HRR) and a 30-minute control (CON) trial. The
constant error (CE) was significantly higher for BIA at each time point and
exercise session (CE = 3.0-4.9% for 60% HRR; 2.5-4.7% for 80% HRR). Conversely,
BIS yielded a nonsignificant CE at each time point and exercise session (CE =
0.9 to 1.1% for 60% HRR; -0.3 to 1.2% for 80% HRR). The standard error of
estimate (SEE) for both exercise sessions ranged from 2.7 to 3.1% and 3.8-4.3%
for BIA and BIS, respectively. The 95% limits of agreement were narrower for BIA
(60% HRR = +/-5.5 to 7.8%; 80% HRR = +/-6.6 to 8.5%) than BIS (60% HRR = +/-8.4
to 9.4%; 80% HRR = +/-8.1 to 10.2%). Results indicate that BIS can be used for
mean group BF% in men at PRE, IP, and 60P time periods. However, BIA yielded a
lower SEE and 95% limits of agreement than BIS. Therefore, BIA provides better
individual estimates of BF% in men, but the CE should be taken into
consideration.
PMID- 28415071
TI - Lower Physical Activity in Persons with Multiple Sclerosis at Increased Fall
Risk: A Cross-sectional Study.
AB - Persons with multiple sclerosis (MS) often report being afraid of falling, and
this may have effects on physical activity (PA) engagement. This study
investigated PA levels in persons with MS as a function of fall risk categories.
Forty-seven persons with MS participated in the study and were categorized into
either increased fall risk (IFR; n = 21; 55.5 +/- 9.0 years) or normal fall risk
(NFR; n = 26; 51.2 +/- 12.9 years) groups based on scores from the Activities
Balance Confidence scale. PA was measured by accelerometer and expressed as
average steps per day, and time spent in sedentary behavior, light PA, and
moderate to vigorous physical activity over the course of 7 consecutive days.
Univariate and covariate analyses were used to compare the differences in PA
between fall risk groups. The average steps per day of the NFR group was
significant higher compared with the IFR group (6024 +/- 2533.1 vs. 2599 +/-
1622.7 steps; P < 0.001), and the difference remained after controlling for
disability level (5351 +/- 2298.6 vs. 3432 +/- 2363.6 steps; P = 0.016). There
were no differences in light PA and moderate to vigorous physical activity
between groups after controlling for disability level. Persons with MS at IFR
accumulate fewer steps per day compared with those at NFR. This underscores the
need for well-designed interventions targeting walking in this population who are
far from the recommended 10,000 steps, particularly those with IFR.
PMID- 28415072
TI - Changing Perception: Outcomes from a Physical Medicine and Rehabilitation Medical
Student Interest Fair.
AB - Exposure to the field of Physical Medicine and Rehabilitation (PM&R) is limited
in the curricula of many medical schools. As a result, many students lack
awareness of the field and may therefore ultimately choose different careers. A
medical student PM&R career fair was held on October 13th, 2015 at the University
of Pittsburgh, and several local medical schools were invited to participate.
Seven stations were deployed to highlight various aspects of PM&R careers. A
total of 57 medical students attended, representing five different campuses
across three states, with 29 of the reported medical students still within their
first or second year of medical education. Self-reported interest and
understanding of PM&R significantly increased in those attending the fair
compared to baseline, with nearly half requesting further opportunities for
faculty mentorship. These results indicate that PM&R interest fairs may be a
means to further student understanding and awareness of PM&R while providing an
opportunity to become more involved in the field.
PMID- 28415073
TI - Chemical-induced disease relation extraction via convolutional neural network.
AB - : This article describes our work on the BioCreative-V chemical-disease relation
(CDR) extraction task, which employed a maximum entropy (ME) model and a
convolutional neural network model for relation extraction at inter- and intra
sentence level, respectively. In our work, relation extraction between entity
concepts in documents was simplified to relation extraction between entity
mentions. We first constructed pairs of chemical and disease mentions as relation
instances for training and testing stages, then we trained and applied the ME
model and the convolutional neural network model for inter- and intra-sentence
level, respectively. Finally, we merged the classification results from mention
level to document level to acquire the final relations between chemical and
disease concepts. The evaluation on the BioCreative-V CDR corpus shows the
effectiveness of our proposed approach. Database URL:
http://www.biocreative.org/resources/corpora/biocreative-v-cdr-corpus/.
PMID- 28415074
TI - NaviCom: a web application to create interactive molecular network portraits
using multi-level omics data.
AB - : Human diseases such as cancer are routinely characterized by high-throughput
molecular technologies, and multi-level omics data are accumulated in public
databases at increasing rate. Retrieval and visualization of these data in the
context of molecular network maps can provide insights into the pattern of
regulation of molecular functions reflected by an omics profile. In order to make
this task easy, we developed NaviCom, a Python package and web platform for
visualization of multi-level omics data on top of biological network maps.
NaviCom is bridging the gap between cBioPortal, the most used resource of large
scale cancer omics data and NaviCell, a data visualization web service that
contains several molecular network map collections. NaviCom proposes several
standardized modes of data display on top of molecular network maps, allowing
addressing specific biological questions. We illustrate how users can easily
create interactive network-based cancer molecular portraits via NaviCom web
interface using the maps of Atlas of Cancer Signalling Network (ACSN) and other
maps. Analysis of these molecular portraits can help in formulating a scientific
hypothesis on the molecular mechanisms deregulated in the studied disease.
Database URL: NaviCom is available at https://navicom.curie.fr.
PMID- 28415082
TI - P210Long- term outcome of primary mitral valve prolapse: results from a
population of 250 patients referred to a tertiary cardiovascular center.
AB - Background: Outcome of Mitral Valve Prolapse (MVP) was controversial for long
time. Many studies reported great differences in the incidence of cardiovascular
events due, above all, to heterogeneous and small studied populations. Most of
theme were also published to late '80 of the last century till early '00.
Purpose: To make a contemporary survey on the incidence of cardiovascular events
in a selected population of patients affected by primary MVP referred to a
tertiary cardiovascular center for the medical and surgical care of valvular
heart disease. Methods: We reviewed our MVP database; patients with at least 2
cardiologic evaluations inclusive of echocardiographic examination and at least 6
months follow up were enrolled. A total of 250 patients (126 F) were selected.
Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up
time was 100 months (8,33 yrs). Results: At the first medical and
echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR),
104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a
severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA
III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP
(94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was
present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%)
and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior
mitral annulus diameter was 37 mm. During the follow up 7 patients died of non
cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary
syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally
we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture
occurred during the follow up in most cases concerning mitral chordae linked to
posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an
evolution of the clinical condition of 48 patients (19.2%) which developed
Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of
the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at
the initial evaluation). A total of 45 patients (18%) underwent mitral valve
surgery. 40 needed in-hospital treatment in most cases due to the development of
atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred
in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6
(2.4%). The overall cardiovascular event rate was 4,33/100 patients-year,
significantly higher than reported in community based studies. Conclusions: The
prognosis of a MVP population referred to a tertiary cardiovascular center is not
benign. The most frequent complications are progression of MR and MV surgery.
Sudden death is also more frequent than in general population. More studies are
needed to identify what patients with MVP are at risk for it.
PMID- 28415075
TI - HopBase: a unified resource for Humulus genomics.
AB - Hop (Humulus lupulus L. var lupulus) is a dioecious plant of worldwide
significance, used primarily for bittering and flavoring in brewing beer. Studies
on the medicinal properties of several unique compounds produced by hop have led
to additional interest from pharmacy and healthcare industries as well as
livestock production as a natural antibiotic. Genomic research in hop has
resulted a published draft genome and transcriptome assemblies. As research into
the genomics of hop has gained interest, there is a critical need for centralized
online genomic resources. To support the growing research community, we report
the development of an online resource "HopBase.org." In addition to providing a
gene annotation to the existing Shinsuwase draft genome, HopBase makes available
genome assemblies and annotations for both the cultivar "Teamaker" and male hop
accession number USDA 21422M. These genome assemblies, gene annotations, along
with other common data, coupled with a genome browser and BLAST database enable
the hop community to enter the genomic age. The HopBase genomic resource is
accessible at http://hopbase.org and http://hopbase.cgrb.oregonstate.edu.
PMID- 28415083
TI - P235Relation between myocardial deformation by three-dimensional speckle tracking
analysis , control of the hypertension and functional capacity in patients with
systemic hypertension.
AB - The purpose of this study was to investigate left ventricular (LV) function in
hypertensive patients by 3-dimensional (3D) speckle tracking imaging, and
determine the relation between the LV mechanics and functional capacity in this
population. This cross-sectional study included 20 treated subjects with well
controlled arterial hypertension (group B) and 20 treated participants with
uncontrolled hypertension (group A), adjusted by gender and age. All the subjects
underwent 24-hour blood pressure monitoring, complete 2-dimensional and 3D
examination, and exercise testing. Patients had similar 3D LV ejection fraction.
LV mass was higher in group of uncontrolled hypertension (154.71 +/- 49.7 g/m2
versus 147.12+/-44.8 g/m2 p < 0.01), as well as E/E'ratio (11.4 versus 8.9, p
=0.02). 3D global longitudinal and circumferential strain and strain rate were
significantly decreased in patients with inadequately controlled hypertension (LS
16.25% versus -19.24%, p=0.007, L-SR -0.97/sec versus -1.48/sec, p=0.04, CS
17.89%versus -21.76%, p=0.04, respectively), while the difference of radial
strain and strain rate did not reach statistical significance. Group A of
patients had also a significantly lower functional capacity (mean duration of
test 13,3 min. versus 17,4 min, nr. of METS 9.4 versus 13.7). Duration of
exercise was independently associated with LV mass , mean BP at daytime , E/E'
ratio and 3D global longitudinal strain (beta = 0.34, p = 0.02) in the whole
hypertensive population in our study. In conclusion, LV longitudinal strain and
functional capacity are significantly impaired in the patients with uncontrolled
hypertension in comparison with the well-controlled hypertensive patients and are
independently associated.
PMID- 28415084
TI - P260Right cardiac chambers remodeling in marathon and ultra-trail athletes
detected by speckle-tracking echocardiography.
AB - Background: Strenuous and chronic exercise training can have detrimental effects
on cardiac morphology and function. Our aim was to evaluate the cardiac
adaptation between 2 different specialties' endurance athletes: marathon runners
(M) and ultra-trailers (UT). Methods: 47 M (age 45+/-7, men 32; training: 18 (9
53) years*days/week), 41 UT (age 42+/-9, men 38, training: 30 (15-66)
years*days/week) were submitted in rest condition to conventional 2D
echocardiography and Speckle-Tracking echo (STE) (Beyond Diogenes 2.0, AMID)
during agonistic season and compared with 15 age matched sedentary individuals
(S) (age 43+/-6, men 10). Results: Left ventricle (LV) global longitudinal strain
(GLS) and global radial strain (GRS) were increased in M and UT compared to S
(see table) without differences in LV anatomy and function. Right ventricle (RV)
end-diastolic area (p=0.026), fractional area changing (p=0.008) and RV GLS were
increased in UT compared to M. Moreover UT showed larger right atrium (RA) volume
compared to M (p=0.03) and S (p=0.003). RA GLS was reduced in UT compared to M
while the RA Global Circumferential Strain was significantly increased in UT.
After adjusted for age, sex and HR as covariates, UT showed a reduced RA GLS (OR
0.907; CI 0.856-0.961) and increased RV FAC (OR 1.172; CI: 1.044-1.317) compared
to M; while when compared to S subjects, UT showed increased RA volume (OR 1.048;
CI 1.002-1.096) and RV GLS (OR 0.667; CI 0.490-0.907). Conclusion: UT showed
higher RV and RA morphological and functional remodeling in comparison with M. 2D
STE is a useful tool to investigate the deformation dynamic in different sport
specialties. Further studies will be necessary to clarify the long-term
consequences for cardiac health due to myocardial perturbations. : MUTSpLV GLS
28.59+/-3.43*-27.64+/-4.18*-24.82+/-4.53<0.05LV GRS69.85+/-8.94*66.59+/
11.19*56.27+/-16.25<0.001RV GLS-25.60+/-10.54-30.41+/-4.38*-27.10+/-4.64<0.05RA
GLS37.15+/-13.4931.65+/-9.60*35.37+/-9.99<0.05RA GCS17.46+/-6.4222.28+/
8.97*23.37+/-6.47<0.01.
PMID- 28415098
TI - P569Diastolic dyssynchrony is associated with exercise intolerance in
hypertensive patients with left ventricular hypertrophy.
AB - Background: Left ventricular hypertrophy (LVH) is associated with intra
ventricular dyssynchrony at systolic phase during exercise in hypertensive
patients. However, dypsnea on exertion is much more correlated with diastolic
phase. We investigated whether LVH is associated with diastolic dyssynchrony
during exercise in patients with hypertension. Methods: Ninety hypertensive
patients with exertional dyspnea and 30 control individuals were enrolled.
Exercise stress echocardiography was performed using a symptom limited,
multistage supine bicycle test. To evaluate the diastolic dyssynchrony of LV, we
calculated the standard deviation (SD) of the averaged time from Q wave to
myocardial early diastolic velocity in 12 segments. (TPe-SD, ms). Therefore,
diastolic dyssynchrony index was SD of TPe. And also, we applied modified SD
(SD/heart rate). Results: There was no significant difference in systolic blood
pressure (BP) and heart rate between the two groups. TPe-SD was significantly
higher in patients with LVH at rest (27 +/- 11.0 vs. 18.7 +/- 7.4 ms, p<0.005)
with exaggeration of the degree at peak exercise (42.0 +/- 10.6 vs. 30.6 +/- 12.4
ms, p<0.001). When applying modified SD, the difference is much more increased
(80.0 +/- 17.6 vs. 49.0 +/- 21.3 ms, p <0.001). Multiple regression analysis
showed LV mass index (beta=0.515, P=0.001) and E/E' at peak exercise (beta=
0.253, P=0.025) were independently associated with LV dyssynchrony during
diastolic phase when controlled for age, sex, and systolic BP at peak exercise.
Conclusion: Intra-ventricular diastolic dyssynchrony during exercise is
significantly associated with exercise duration in hypertensive patients with
LVH. And this result could explain that the patients with exertional dyspnea are
more common in LVH group. : Univariate and multivariate analysis forUnivariate
AnalysisMultivariate Analysisbetap valuebetap valueAge-0.288*0.037
0.355*0.001Sex0.161*0.0200.250*0.034LVMI (g/m2)-0.787*0.008-0.515*0.001LAVI(mL)
0.4400.065-0.1750.075E' at peak ex.0.2160.589Diastolic dyssynchrony-0.725*0.030
0.253*0.025S' at peak ex.0.7100.073 LVMI, left ventricular mass index; LAVI, left
atrium volume index; E, early diastolic mitral inflow velocity; E', early
diastolic longitudinal tissue velocity; S', early systolic longitudinal tissue
velocity. : Univariate and multivariate analysis for. : LVMI, left ventricular
mass index; LAVI, left atrium volume index; E, early diastolic mitral inflow
velocity; E', early diastolic longitudinal tissue velocity; S', early systolic
longitudinal tissue velocity.
PMID- 28415097
TI - P544The importance of contractile reserve when assessing asymptomatic patients
with aortic stenosis.
AB - Asymptomatic patients may exhibit symptoms during objective exercise testing, but
whether symptoms are due to the obstructively of the valve (typified by the mean
gradient) or underlying ventricular function remains unknown. While the mean
gradient is an easy parameter to measure no consensus about the measurement of
contractile reserve exists. Longitudinal abnormalities may occur in the presence
of a normal ejection fraction and the augmentation of these parameters is poorly
described. To obtain an objective regarding patients exercise ability is best
determined using cardiopulmonary exercise testing. We therefore examined
echocardiographic predictors of exercise ability during cardiopulmonary exercise
testing.24 asymptomatic patients with moderate to severe or severe aortic
stenosis and preserved ejection fraction underwent stress echocardiography with
simultaneous cardiopulmonary exercise testing. The primary assessment of exercise
ability was the VO2peak and OUES. Echocardiography was measured at rest and
during maximal exercise (defined as RER > 1)OUES and VO2peak showed a poor
relationship with conventional parameters of severity including peak and mean
gradients, AVA and dimensionless index, resting systolic function (by EF and
TDI). During exercise systolic augmentation had a good relationship with exercise
ability but the exercise mean gradient and exercise LVEF did not.Longitudinal
systolic function and particularly systolic augmentation is the strongest
predictor of exercise ability when compared to conventional measures of
severity.VO2peakOUESS' exerciseRho=0.69 (p=0.001)R= 0.71 (p=0.001)S' restRho=0.52
(p=0.01)R= 0.44 (p=ns)Rest AV max VRho= 0.09 (p=ns)R= -0.08 (p=ns)Rest AV mean
PGRho= 0.34 (p=ns)R=-0.10 (p=ns)Exercise AV max VRho=0.43 (p=0.05)R=0.23
(p=ns)Exercise AVmean PGRho= 0.51 (p=0.001)R=0.26 (p=ns)Rest AVARho=0.40
(p=ns)Rho=0.46 (p=0.04)Dimensionless indexRho=0.15 (p=ns)R=0.13 (p=ns)LVEF
restRho=-0.18 (p=ns)R=-0.32 (p=ns)LVEF exerciseRho=0.18 (p=ns)R=0.17 (p=ns)S' -
systolic velocity; V - velocity; AV - aortic valve; AVA- aortic valve area; LVEF
left ventricular ejection fraction.
PMID- 28415099
TI - P594Contrast transthoracic echocardiography as a gatekeeper for patent foramen
ovale closure.
AB - Background.: The presence of patent foramen ovale (PFO) has been linked to many
illness, including cryptogenic stroke, transient ischemic attack, migraine,
platypnea-orthodeoxia syndrome and decompression sickness in scuba divers.
Transesophageal echocardiography is the gold standard technique for the
visualization of atrial septal anatomy, but it is a secondary level exam, not
always available, with additional associated costs and not completely free from
procedural risks. Standard transthoracic echocardiography (TTE) has a too low
sensitivity for PFO screening. Purpose.: The aim of the study was to assess the
role of TTE associated with agitated saline contrast injection (contrast-TTE) as
a gatekeeper for the identification of PFO in a large cohort of patients
undergoing selection for percutaneous closure. Methods.: A total of 200 patients
undergoing a diagnostic work-up for the identification of PFO was imaged by
contrast-TTE at rest and after provocative maneuvers (PM: Valsalva in all cases).
Contrast TTE was graded from 0 to 4 on the bases of bubbles counting (0: no
bubbles; 1: < 10 bubbles; 2: 10-30 bubbles; 3: >30 bubbles; 4: complete LV
opacification). PFO closure was performed after a consensual clinical decision by
the cardiologist and the neurologist taking into account comprehensive imaging,
clinical evaluation and thrombophilia screening. PFO closure was always monitored
by intracardiac echocardiography. Results.: At baseline contrast TTE was positive
(>=2) in 34 patients (17%) while contrast TTE with PM was positive in 94 cases
(47%). 27 out of 200 patients (14%) had an interatrial septal aneurysms. PFO
closure was performed in 34 cases (17%). All of these had severe right-to-left
shunting (>=3) at contrast TTE and 9 cases had also an interatrial septal
aneurysms. The procedure was aborted in only 1 patient due to a complex defect
anatomy. Conclusion.: Contrast TTE with PM may be not only considered an accurate
tool for the detection of PFO but may be also inserted in the diagnostic work- up
as a primary gatekeeper for percutaneous closure. Severe shunting at contrast TTE
influences final decision making in a large cohort of cases undergoing screening
for PFO closure.
PMID- 28415102
TI - P650Influence of fetunin-a level on progression of calcific aortic valve stenosis
The COFRASA - GENERAC Study.
AB - Background.: In recent years, pathophysiology of aortic stenosis (AS) has been
considered as a possibly active inflammatory process, but its determinants remain
unclear. Calcium tissue deposition observed in dilaysis patients have been linked
to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is
thus suspected to play a role in development of aortic stenosis. Purpose.: To
assess correlation between Fetuin-A level and AS progression in a prospective
cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC
(clinicalTrial.gov_number_NCT00647088). Methods.: A comprehensive clinical
evaluation and Fetuin-A plasma level measurement was performed at baseline. AS
severity was evaluated at baseline and yearly thereafter using echocardiography
(mean pressure gradient (MPG)) and computed tomography (degree of aortic valve
calcification or AVC). Annual progression was calculated as [(final measurement -
baseline measurement)/follow-up duration] for both MPG and AVC measurements.
Results.: We enrolled 296 patients with at least 1 year of follow-up. Mean age
was 74+/-10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55+/-0.15 g/L.
After a mean follow-up of 3.0+/-1.7 years, no correlation was found between AS
progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC
(r=0.014, p=0.82). This was also true when comparing patients with lower level of
Fetuin-A (<=0.53 g/L, the median in our cohort) with patients with higher
level(+3+/-5 mmHg/year (median 2, [0-5] vs +4+/-4 mmHg/year (median 2, [1-6])
p=0.06, and +205+/-290 AUC/year (median 122, [32-269]) vs +240+/-310 AUC/year
(median 145, [50-313], p=0.24). This was true also after adjustment for baseline
severity and valve antomy. Conclusions.: In our prospective cohortot of AS
patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS
progression. Despite strong capacity to inhibit ectopic calcium deposition,
Fetuin-A plasma level seems to have minor influence on AS progression.
PMID- 28415103
TI - P673Improvement of arterial stiffness and myocardial deformation in patients with
poorly controlled diabetes mellitus type 2 after optimization of antidiabetic
medication.
AB - Background: Arterial stiffness is associated with increased risk for
cardiovascular disease. The purpose of this study is to investigate the arterial
stiffness and myocardial deformation in patients with poorly controlled diabetes
mellitus type 2 before and after glycemic control by optimal medication. Methods:
In 50 patients with uncontrolled type 2 diabetes(age:52+/-10years)and 25 controls
of similar age and sex and no atherosclerotic risk factors we measured at
baseline and 6 months after glycemic control a) carotid-femoral pulse wave
velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP
mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed)
b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal
strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate,
twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using
speckle tracking echocardiography.The degree of LV untwisting was calculated as
the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw
UntwMVO)and between peak twisting and untwisting at peak and end of the mitral
inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual
arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield
imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of
reduced endothelial glucocalyx thickness because of a deeper RBC penetration in
the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and
percentage difference of FMD (FMD%). Results: Compared to controls,diabetics had
higher PWVa(10.3+/-2.2 vs. 8.1+/-1.9), AI(27.9+/-15 vs. 19.4+/-14.7), PWVc(11.8+/
3.2 vs. 8.8+/-1.3),cSBP(136+/-20 vs. 119+/-18),PBR (2.1+/-0.2 vs 1.89+/-0.1)and
lower GLS(-15+/-3 vs. -18+/-3),LongSr(-0.78+/-0.1 vs. -0.96+/-0.2),LongSrE(0.77+/
0.29 vs. 1.2+/-0.3),S',E' and E/A(p<0.05 for all comparisons). Baseline FMD was
related with Untw at peak E%(r=0,65, p<0.05). Six months after the modification
of antidiabetic medication all patients achieved glycaemic control and there was
a reduction of PWVc(12.3+/-2.9 vs. 11.3+/-3.2,p<0.05) in parallel with a increase
of Untw velocity (-73+/-27 vs. -98+/-43,p<0.05),Untw MVO%(20+/-9 vs. 30+/-2),Untw
peak E% (40+/-14 vs. 50+/-16)and FMD%(7.8+/-3 vs. 13.6+/-11,p<0.01).Reduced PWVc
was related with reduced SBP(r=0.62),cSBP(r=0.55)and increased LongsrE(r=-0.50),
Untw at end E(r=-0.56)respectively(p<0.05 for all associations). Conclusion:
Glycaemic control after optimizing medical treatment improves arterial stiffness,
LV myocardial strain, twisting and untwisting velocity in diabetics.
PMID- 28415104
TI - P697New indices for a best quantification of left ventricular function in heart
valve diseases.
AB - : Aims. : The Assessment of left ventricular (LV) function remains a clinical
challenge especially in patients with preserved LV ejection fraction (EF) and
valvular heart diseases (VHD). Mechanical dispersion is supposed to be a strong
predictor of events and, to be related to the extent of fibrosis. Regional
cardiac work is a new validated and very promising approach to quantify LV
function. : We investigated the differences in mechanical dispersions and global
LV work (totW) and wasted work fraction (WWF) in normal subjects and in patients
with severe primary mitral regurgitation (MR) and severe aortic stenosis (AS).
Methods and Results: A complete transthoracic echocardiography was performed in
21 normal subject, 97 patients with severe valvulopathy (47 AS, 50 MR) and
preserved LV EF. Segmental strain analysis was performed in all patients and the
dispersion of regional LV strain curves was computed automatically considering
peaks and integrals. The LV-pressure was estimated non-invasively using a
standard waveform fitted to valvular events and scaled to systolic blood
pressure. Using pressure-strain loops, regional cardiac work indices were
computed. : LVEF was 66+/-12 in controls, 65+/-9 in MR and 65+/-4% in AS
(p=0.125). Global longitudinal strain was -23+/-2.7 in controls, -24+/-2.9 in MR
and -18+/-3.2% in AS (p < 0.001). The mechanical dispersion was 38+/-7.9 in
controls, 36+/-11 in MR, and much higher in the hypertrophied LV of the AS: 60+/
19ms (p < 0.001). Cardiac work was 2200+/-260 in controls, 2100+/-270 in MR, and
much lower in AS: 1700+/-280 mmHg.% (p < 0.001). The wasted work fraction (WWF)
was even more describing how different the LV systolic function is in the 3
groups (figure1). Conclusion: Longitudinal strain data are robusted and new
indices might be calculated based on them. These seem especially promising for a
more pathophysiological driven analyzing of LV-functions. Abstract P697 Figure. :
Abstract P697 Figure.
PMID- 28415115
TI - P981Lvot area measurement using gated ct data reclassifies aortic stenosis
severity as graded by echocardiography.
AB - Background: Measurement of left ventricular outflow tract (LVOT) diameter and
area for estimation of aortic valve area (AVA) using transthoracic
echocardiography (TTE) and the continuity equation assumes circular LVOT. The use
of direct planimetric measurement of LVOT area by gated-CT can theoretically
improve accuracy of AVA calculation. Purpose: We aim to assess reproducibility of
LVOT echo measurement and its correlation and agreement with Gated CT
measurements. In the subgroup with aortic stenosis (AS) we secondarily assessed
the potential change in AS severity using LVOT area by CT instead of TTE in the
continuity equation. Methods: We retrospectively studied 93 patients, 43 of whom
with severe AS. LVOT Area was measured with 2D TTE by 2 expert echocardiographers
and gated-CT by 2 expert radiologists; inter-reader agreement and inter-method
(Echo vs gated CT) agreement and correlation were measured. Finally we used the
measurement of CT scan in the continuity equation instead of TTE measurement to
assess potential reclassification of AS severity. Results: Mean age was 78+/-11.
Table shows inter-reader and inter-method agreement and correlation. : The
correlation between 2 echocardiophers for LVOT measurements was good (rho = 0,77)
although not perfect. Out of 43 severe AS, defined as AVA<1 cm2 using TTE in the
continuity equation, 18 were reclassified by gated-CT LVOT measurements into
moderate AS. This was due to gated-CT LVOT area resulting on average 1.4 cm2
larger than LVOT area by TTE. Conclusion: LVOT is elliptical and TTE tends to
underestimate LVOT area and AVA due to the measurement of the shorter diameter of
this ellipse. CT scan can provide more geometrically accurate measurement and
requires different cut-offs compared with traditional TTE AVA measurement. By the
way, in the current study the LVOT area by CT was on average 38% larger of the
LVOT area measured by TTE. Such correcting factor (increase TTE LVOT area by 38%)
should apparently be used to assess anatomical true planimetric area to be
compared with gated-CT LVOT. : summary tableTTE Inter-reader correlation LVOT
area (Spearman rho)0.77TTE reader A vs CT 3-chamber equivalent correlation
(Spearman rho)0.49TTE reader B vs CT 3-chamber equivalent correlation (Spearman
rho)0.38TTE reader A area vs CT planimetric area correlation (Spearman
rho)0.41TTE reader B area vs CT planimetric area correlation (Spearman
rho)0.31Mean LVOT Area by TTE reader A3,60SD 0,6038%Mean LVOT Area by CT
scan4,99SD 0,98 Abstract P981 Figure. : summary table. : Abstract P981 Figure.
PMID- 28415116
TI - P1007Aortic root diameters and aortic regurgitation in hypertensive patients and
normal subjects.
AB - Purpose: : The association between aortic root diameters and aortic regurgitation
in hypertension (HT) is disputed with lack of understanding of the underline
mehanisms lT. We investigate the relationship between aortic root diameters and
aortic regurgitation in newly diagnosed and never treated hypertensive patients
and in a group healthy subjects. Method: Participants were 175 hypertensives (42
F and 133 M) and 305 normotensives (134 F, 168 M) age matched (mean age 52.4+/-13
vs 52.6 +/-15.2 years). Antropometric, office blood pressure (BP) measurements, a
comprehensive echocardiography and local carotid stiffness study were performed.
Aortic measures for annulus, sinuses of Valsalva, sinotubular junction and
ascending aorta were taken in late diastole according to the leading edge method.
The sinotubular junction/annulus ratio was calculated. Results: Hypertensive
patients had significantly higher body surface area (BSA), systolic (SBP) and
diastolic pressure (DBP), mean arterial pressure (MAP) and pulse?pressure (PP)
(p<0.0001) than normotensives. Annulus and sinotubular junction diameters,
indexed by BSA and after adjustment for gender, MAP, heart rate?(HR), were
significantly higher in normotensives than hypertensives. Considering subjects
with aortic regurgitation (trivial or mild) we found a higher prevalence
in?hypertensives (25.7 % vs 10.2%, p<0.0001). Moreover in hypertensives we found
no difference in aortic diameters between patients with or without aortic
regurgitation?but ascending aorta /BSA (p=0.002) whereas in healthy subjects
aortic regurgitation was associated with larger aortic root diameters included
sinotubular junction/annulus ratio (table 1). In the logistic regression
analysis, aortic regurgitation was associated with age, gender, BP parameters,
one point carotid stiffness parameters. Conclusions: Hypertensive patients had
smaller indexed aortic root dimensions than normal subjects but they had heigher
prevalence of trivial-mild aortic regurgitation in contrast to normotensives who
had aortic regurgitation combined with larger aortic diameters.
PMID- 28415117
TI - P1033Echocardiographic predictive model of new-onset postoperative atrial
fibrillation after abdominal surgery.
AB - Background: and purpose: Postoperative atrial fibrillation (POAF) is a frequent
complication post high-risk abdominal surgery in elderly patients. This study
aimed to develop a predictive model of POAF based on preoperative transthoracic
echocardiography (TTE) findings in these patients. Methods: We conducted a
prospective study of 300 consecutive patients, age >= 65 years (mean age 72+/-6
years, 61% men), who underwent high-risk abdominal surgery under general
anesthesia. Preoperative TTE was performed in all patients, including tissue
Doppler imaging (TDI). We measured the time interval between the onset of the P
wave on ECG and a point of the peak-A wave on TDI from the lateral mitral annulus
(PA lateral) and septal mitral annulus (PA septal). Left atrial (LA) dyssynchrony
was measured by subtracting the PA septal from PA lateral. Right ventricular
systolic pressure was estimated by using the tricuspid regurgitation jet (TRJ)
Doppler velocity method. The primary endpoint was the occurance of new-onset
POAF. Results: Thirty-seven (12%) patients developed POAF. Multiple
echocardiographic parameters were measured and tested in different combinations.
The final model included the following variables with cutoff points predictive of
POAF: PA lateral > 139 ms (69% sensitivity, 92% specificity), LA dyssynchrony >
35 ms (78% sensitivity, 89% specificity), and TRJ Doppler velocity >2.6 m/s (89%
sensitivity, 64% specificity). A value of 0 was assigned when the result was
below the cutoff point and a value of 1 if above the cutoff point. Coding of
these three variables in the following order: PA lateral- TRJ Doppler- left
atrial dyssynchrony can predict the probability of POAF. The model showed a
postive predictive value of 79% and a negative predictive value of 95%.
Conclusion: A model using three echocardiographic variables: PA lateral, LA
dyssynchrony and TRJ Doppler velocity, can predict the incidence of POAF after
high-risk abdominal surgery. The model can be used preoperatively to identify
high-risk patients that would need aggressive prophylactic treatment. : PA
lateral >139 ms-TRJ Doppler velocity >2.6 m/s-LA dyssynchrony >35 msProbability
of POAF0- 0- 0; 0- 1- 0No0- 0- 1; 0- 1- 1; 1- 0- 0; 1- 0- 1; 1- 1- 0; 1- 1- 1Yes.
PMID- 28415120
TI - P1088Match and mismatch between opening area and resistance in mild and moderate
rheumatic mitral stenosis.
AB - Background: Mitral valve resistance (MVR) is a hemodynamic consequence of mitral
stenosis but it has no clear threshold and it has a shortage of data to be
reliable. Purpose: is to investigate match and mismatch between opening area and
resistance especially in patients with moderate and mild mitral stenosis.
Materials: This cross section case control study comprised 88 patients with
moderate and mild rheumatic mitral stenosis. Transthorathic echocardiographic
study estimated: mitral valve area (MVA) both by planimerty (2D) and pressure
half time (PHT), mitral valve score (MVS), mean transmitral pressure gradient
(MPG), diastolic filling time(DFT), left ventricular out flow tract diameter
(LVOTd) and velocity time integral (LVOT vti) , the MVR was calculated as:
MPG/aortic flow ratio [(LVOTd) (LVOTvti)/ DFT] in dynes.sec.cm5, NYHA function
class of all patients was estimated. We classified our patients into 2 groups,
group 1 (51 patients) with matched MVR and group 2 (37 patients) with unmatched
MVR (unexpected high MVR in relation to valve area). Methods: Patients with
moderate mitral stenosis have MVR less than 105 dynes.sec/cm5, while patient with
mild mitral stenosis have MVR less than 76 dynes.sec/cm5 this is in the matched
group, but there are patients with unmatched higher MVR. Group 2 compared to
group 1; had higher NYHA function class (1.4+/-0.6 vs. 1.2+/-0.4, P < 0.05), MVS
(8.1+/-1.8 vs 7+/-0.9, P < 0.05), MPG (11,3+/-3.7 vs.7.8+/-2.5 mmHg, P < 0.01)
and higher MVR (122.37+/-29.87 vs. 67.18+/-20.12 dynes.sec/cm5 , P < 0.01), MVR
showed positive correlation with MVS (r=0.5, P < 0.05), Step wise logistic
regression analysis showed that MVS is the only independent predictor of the MVR
severity in the mismatched (unexpected high) group , so the higher the MVS the
higher the expected MVR whatever the MVA is ; (B+/-SE=6.997+/-2.826, t=2.476, 95%
CI 1.241+/-12.752 with an odds ratio=0.412, P < 0.05). Conclusion: It would make
much more sense to investigate match and mismatch between opening area and
resistance in rheumatic mitral stenosis, the only independent predictor of
mismatch is the mitral valve score.
PMID- 28415121
TI - P1113Relationship between left atrium and hypertensive retinopathy in patients
with systemic hypertension: a real-time three-dimensional echocardiography-based
study.
AB - Background: The fundoscopic examination of hypertensive patients, which is an
established hypertension-related target organ damage (TOD), tends to be
underutilized in clinical practice. We sought to investigate the relationship
between retinal alterations and left atrium (LA) volumes by means of real-time,
three-dimensional echocardiography (RT3DE), which is the most pivotal predictor
of diastolic dysfunction. Methods: Our population consisted of 88 consecutive
essential hypertensive patients (age 59.2 +/- 1.2 years, 53 females) without
overt cardiovascular disease. All subjects underwent a fundoscopy examination and
were distributed into five groups according to the Keith-Wagener-Barker (KWB)
classification. Comprehensive transthoracic echocardiographic and RT3DE
measurements were performed to assess LA volumes and phasic functions. Results:
The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients,
respectively) did not differ with regards to age, gender, or metabolic profile.
There were no significant differences between groups with regards to parameters
reflecting left ventricle (LV) systolic function and diastolic dysfunctions in
conventional echocardiography, except isovolemic relaxation time (IVRT) and
deceleration time (DT). Nevertheless, patients in the higher KWB category had
higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial
contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001)
regarding RT3DE (table 1). There is also a significant relationship between
preatrial contraction volume and duration of HT (r: 0.67, p<0.001). Conclusion:
Patients with arterial hypertension were found to have increased LA volume and
impaired atrial compliance and contractility. Moreover, RT3DE identifies early
functional LA changes in these patients better than conventional
echocardiography. Assessment of the hypertensive patient by using RT3DE atrial
volume analysis may facilitate early recognition of TOD, which is such a crucial
determinant of cardiovascular mortality and morbidity in patients with systemic
hypertension.
PMID- 28415122
TI - P1138Cardiac shear wave velocity in healthy individuals.
AB - Background: The closure of the valves generates shear waves in the heart walls.
The propagation velocity of shear waves relates to stiffness. This could
potentially be used to estimate the stiffness of the myocardium, with huge
potential implications in pathologies characterized by a deterioration of the
diastolic properties of the left ventricle. In an earlier phantom study we
already validated shear wave tracking with a clinical ultrasound system in
cardiac mode. Purpose: In this study we aimed to measure the shear waves velocity
in normal individuals. Methods: 12 healthy volunteers, mean age=37+/-10, 33%
females, were investigated using a clinical scanner (Philips iE33), equipped with
a S5-1 probe, using a clinical tissue Doppler (TDI) application. ECG and
phonocardiogram (PCG) were synchronously recorded. We achieved a TDI frame rate
of >500Hz by carefully tuning normal system settings. Data were processed offline
in Philips Qlab 8 to extract tissue velocity along a virtual M-mode line in the
basal third of the interventricular septum, in parasternal long axis view. This
tissue velocity showed a propagating wave pattern after closure of the valves.
The slope of the wave front velocity in a space-time panel was measured to obtain
the shear wave propagation velocity. The velocity of the shear waves induced by
the closure of the mitral valve (1st heart sound) and aortic valve (2nd heart
sound) was averaged over 4 heartbeats for every subject. Results: Shear waves
were visible after each closure of the heart valves, synchronous to the heart
sounds. The figure shows one heart cycle of a subject, with the mean velocity
along a virtual M-mode line in the upper panel, synchronous to the ECG signal
(green line) and phonocardiogram (yellow line) in the lower panel. The slope of
the shear waves is marked with dotted lines and the onset of the heart sounds
with white lines. In our healthy volunteer group the mean velocity of the shear
wave induced by mitral valve closure was 4.8+/-0.7m/s, standard error of 0.14
m/s. The mean velocity after aortic valve closure was 3.4+/-0.5m/s, standard
error of 0.09 m/s. We consistently found that for any subject the velocity after
mitral valve closure was higher than after aortic valve closure. Conclusion: The
velocity of the shear waves generated by the closure of the heart valves can be
measured in normal individuals using a clinical TDI application. The shear wave
induced after mitral valve closure was consistently faster than after aortic
valve closure. Abstract P1138 Figure. : Abstract P1138 Figure.
PMID- 28415127
TI - P1246Age-, body size-, and sex-specific reference values for tricuspid valve
apparatus parameters by real-time three-dimensional transthoracic
echocardiography.
AB - Background: and Purpose-Tricuspid valve (TV) apparatus parameters can vary
significantly with demographic and anthropometric factors and could be useful for
clinical decision making. Our aim was to (1) establish the reference values for
TV apparatus parameters using transthoracic three-dimensional (3D)
echocardiography; (2) investigate the influence of age, sex, and body size on TV
anatomy. : Methods-A total of 180 healthy subjects referred in 2015 to our
institution for a screening transthoracic echocardiography were enrolled (mean
age 49.7+17.4 years, range 20 to 80 years: 30 subjects per age decade were
included in the study, 15 for each gender). A real-time zoom 3D image of the TV
and full volume 3D data set were collected from an apical window including TV
using Philips iE33 and GE Vivid E9 Ultrasound Machines. After acquisition, the 3D
data sets were analysed using 3D Qlab and EchoPAC PC softwares. The volumetric
data set was analysed with multiplanar reformatting function to obtain three
simultaneous orthogonal 2D slices (sagittal, coronal and axial planes). The
following TV parameters were obtained and measured: 1. the 3D diastolic annular
diameters (Major and Minor diameters); 2. the 3D diastolic annular area (TDAA);
3. the Tricuspid annular fractional area changes (TAFAC). Results are presented
as mean +/- SD. Differences between and among groups were tested for significance
using the independent samples t-test and ANOVA test for continuous variables.
Univariate Pearson correlation was used to assess the relation between these
parameters and age, and body size. A p <0.05 was considered significant. :
Results- Minor and major diastolic diameters in overall population were 26.1+/
3.9 and 32.3+/-4.1 mm, respectively. Minor diastolic diameter (mDD) (26.9+/-4.2
vs 25.1+/-3.4 mm, p <0.05) and major diastolic diameter (MDD) (33.4+/-4.0 vs
30.9+/-3.8, p <0.05) were significantly different between males and females.
After normalization for BSA, mDD and MDD in overall population were 14.6+/-2.2
and 18.3+/-2.3 mm/m2. Normalized mDD (14.3+/-2.3 vs 14.9+/-2.2 mm/m2, p >0.05)
and normalized MDD (18.1+/-2.4 vs 18.4+/-2.3 mm/m2, p>0.05) did not differ
significantly between males and females. TTDAA and TAFAC in overall population
were 76.7+/-17.3 mm2 and 29.6+/-8.6%. TDAA was significantly different between
males and females (82.5+/-18.3 vs 69.7+/-13.0 mm2, respectively; p < 0.05);
whereas TAFAC did not differ (28.8+/-8.2% vs 30.7+/-8.9%, p>0.05). After
normalization for BSA, TDAA in overall population was 43.3+/-9.0 mm2/m2. Also
normalized TDAA was significantly different between males and females (44.4+/-9.4
vs 42.0+/-8.4 mm2/m2, p < 0.05). mDD, MDD, TDAA and TAFAC showed no correlation
with age (r = 0.16, p 0.04; r = 0.028, p 0.7; r = 0.17, p 0.27; r = 0.16, p 0.16;
respectively). : Conclusion- This study can provide normal reference values for
TV anatomic parameters that may be useful in the clinical practice, considering
the effects of age, sex, and body size.
PMID- 28415128
TI - P1270Effects of blood pressure variability on layer-specific longitudinal strain
in hypertension.
AB - Background: Our previous study showed sub-epicardial longitudinal strain (EpiLS)
was an independent prognostic factor for worse outcome in regular treated
hypertension but not global longitudinal strain (GLS) and sub-endocardial
longitudinal strain (EndLS). Increased blood pressure variability (BPV) has been
found associated with target organ damage in hypertension. However, effects of
BPV on layer-specific longitudinal strain have not been well studied. Purpose:
The aim of this study was to investigate the effects of different blood pressure
parameters on layer-specific longitudinal strain in hypertension. Methods: This
study included 95 patients (57 men, age 65 +/- 12 years) with uncomplicated
hypertension who have been regularly treated for more than 1 year. Speckle
tracking echocardiography was used for measurement of longitudinal deformation
from 3 apical views of left ventricle. GLS was measured by automated function
imaging (AFI). We further divided into sub-endocardial and sub-epicardial
myocardium and measured their longitudinal strain by manual click-and-draw method
and averaged from 3 apical views. Blood pressure parameters included office
systolic blood pressure (SBP), office diastolic blood pressure (DBP), central SBP
and DBP by tonometry, average 24-hour SBP and DBP, and BPV parameters by
ambulatory blood pressure monitor. BPV parameters included standard deviation of
daytime SBP (DSSD), standard deviation of nighttime SBP (NSSD), standard
deviation of daytime DBP (DDSD), and standard deviation of nighttime DBP (NDSD).
Results: We divided subjects into low and high group according to median level of
each strain. No blood pressure parameters were different between low and high
EndLS group except week difference in NDSD (9.0 +/- 3.4 vs. 7.8 +/- 2.0 mmHg, p =
0.051). NSSD (11.2 +/- 4.6 vs. 9.3 +/- 2.9 mmHg, p = 0.027) and NDSD (9.1 +/- 3.4
vs. 7.7 +/- 2.0 mmHg, p = 0.031) were significant increased in low GLS group but
not other parameters. DDSD (10.3 +/- 3.0 vs. 9.0 +/- 2.5 mmHg, p = 0.034), NSSD
(11.4 +/- 4.4 vs. 9.1 +/- 3.1 mmHg, p = 0.006), and NDSD (9.2 +/- 3.2 vs. 7.6 +/-
2.2 mmHg, p = 0.012) were significantly increased in low EpiLS group.
Conclusions: Only BPV parameters were associated with decreased longitudinal
strain in hypertension. Effects of BPV were majorly noted in EpiLS.
PMID- 28415129
TI - P1294Evaluation of right atrium mechanics and relation with loading conditions by
speckle tracking echocardiography.
AB - Purpose: The aim of this study is to evaluate the right atrial (RA) mechanics and
change in echocardiographic parameters used for assessment of RA by examining the
end stage kidney patients before and after the hemodialysis (HD). Methods:
Patients between 18 and 85 years of age, receiving HD for at least 6 months were
included. The echocardiographic images were obtained before and after
hemodialysis therapy. Two-dimensional speckle tracking strain analysis was
performed for right atrium in 62 patients. Reference points for analysis are set
on the "P" waves. RA reservoir, conduit and contraction phase longitudinal strain
(Figure 1) and strain rates (Figure 2) were calculated. The changes in
echocardiographic methods before and after hemodialysis were examined.
Correlation between volume depletion and change in echocardiographic parameters
were calculated. Results: 62 patients (49.7 +/- 16.9 years of age, 22 women) were
included in study. The mean volume of ultrafiltration was 2958.12 +/- 1050.5 ml .
The chamber sizes RA are decreased after hemodialysis (RA major diameter; 4.74 +/
0.62 cm vs. 4.46 +/- 0.54 cm p<0.001, RA area; 13.8 +/- 3.0 cm2 vs. 10.6 +/- 2.8
cm2 p<0.001). Two dimensional speckle tracking analysis showed that; RA reservoir
phase strain (% 45.60 +/- 10.8 vs. % 38.15 +/- 8.11 p<0.001). RA conduit phase
strain rate (-1.46 +/- 0.82 s-1 vs. -1.2 +/- 0.56 s-1 p<0.001) measurements are
volume dependent. RA reservoir phase strain rate (2.25 +/- 0.65 s- vs. 2.5 +/-
0.54 s-1 p:0.091) RA contraction strain (% -16.73 +/- 6.8 vs. % -16.35 +/- 7.1
p:0.835) and RA contraction strain rate (-2.15 +/- 0.95 s-1 vs. -2.21 +/- 0.72 s
1 p:0.596) are volume independent parameters. RA reservoir phase strain (r=0.332.
p:0.008) showed significant correlation with the ultra filtrated volume.
Conclusion: Strain rates of RA reservoir phase and RA contraction and RA
contraction strain are found to be volume independent measurements obtained by
speckle tracking. Explaining RA mechanics with echocardiography is an easy and
repeatable assessment which also elucidates more about cardiac pathophysiology
and hemodynamics of patients. Moreover defining novel volume independent
parameters for evaluation of RA would contribute to clinical perspectives of
patients. Abstract P1294 Figure. : Abstract P1294 Figure.
PMID- 28415131
TI - Retraction of: abstract P71, In vitro and in vivo direct monitoring of miRNA-22
expression in isoproterenol-induced cardiac hypertrophy by bioluminescence
imaging.
PMID- 28415132
TI - Genetic alterations in mesiodens as revealed by targeted next-generation
sequencing and gene co-occurrence network analysis.
AB - OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which
includes a population prevalence of 0.15%-1.9%. Alongside evidence that the
condition is heritable, mutations in single genes have been reported in few human
supernumerary tooth cases. Gene sequencing methods in tradition way are time
consuming and labor-intensive, whereas next-generation sequencing and
bioinformatics are cost-effective for large samples and target sizes. MATERIALS
AND METHODS: We describe the application of a targeted next-generation sequencing
(NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects
were diagnosed on the basis of panoramic radiograph. A total of 101 candidate
genes which were captured custom genes were sequenced on the Illumina HiSeq 2500.
Multistep bioinformatics processing was performed including variant
identification, base calling, and in silico analysis of putative disease-causing
variants. RESULTS: Targeted capture identified 88 non-synonymous, rare, exonic
variants involving 42 of the 101 candidate genes. Moreover, we investigated gene
co-occurrence relationships between the genomic alterations and identified 88
significant relationships among 18 most recurrent driver alterations. CONCLUSION:
Our search for co-occurring genetic alterations revealed that such alterations
interact cooperatively to drive mesiodens. We discovered a gene co-occurrence
network in mesiodens patients with functionally enriched gene groups in the sonic
hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT)
signaling pathways.
PMID- 28415133
TI - ZO-2, a tight junction protein involved in gene expression, proliferation,
apoptosis, and cell size regulation.
AB - ZO-2 is a peripheral tight junction protein that belongs to the membrane
associated guanylate kinase protein family. Here, we explain the modular and
supramodular organization of ZO-2 that allows it to interact with a wide variety
of molecules, including cell-cell adhesion proteins, cytoskeletal components, and
nuclear factors. We also describe how ZO proteins evolved through metazoan
evolution and analyze the intracellular traffic of ZO-2, as well as the roles
played by ZO-2 at the plasma membrane and nucleus that translate into the
regulation of proliferation, cell size, and apoptosis. In addition, we focus on
the impact of ZO-2 expression on male fertility and on maladies like cancer,
cholestasis, and hearing loss.
PMID- 28415134
TI - An Arctic predator-prey system in flux: climate change impacts on coastal space
use by polar bears and ringed seals.
AB - Climate change is impacting different species at different rates, leading to
alterations in biological interactions with ramifications for wider ecosystem
functioning. Understanding these alterations can help improve predictive capacity
and inform management efforts designed to mitigate against negative impacts. We
investigated how the movement and space use patterns of polar bears (Ursus
maritimus) in coastal areas in Svalbard, Norway, have been altered by a sudden
decline in sea ice that occurred in 2006. We also investigated whether the
spatial overlap between polar bears and their traditionally most important prey,
ringed seals (Pusa hispida), has been affected by the sea-ice decline, as polar
bears are dependent on a sea-ice platform for hunting seals. We attached
biotelemetry devices to ringed seals (n = 60, both sexes) and polar bears (n =
67, all females) before (2002-2004) and after (2010-2013) a sudden decline in sea
ice in Svalbard. We used linear mixed-effects models to evaluate the association
of these species to environmental features and an approach based on Time Spent in
Area to investigate changes in spatial overlap between the two species. Following
the sea-ice reduction, polar bears spent the same amount of time close to tidal
glacier fronts in the spring but less time in these areas during the summer and
autumn. However, ringed seals did not alter their association with glacier fronts
during summer, leading to a major decrease in spatial overlap values between
these species in Svalbard's coastal areas. Polar bears now move greater distances
daily and spend more time close to ground-nesting bird colonies, where bear
predation can have substantial local effects. Our results indicate that sea-ice
declines have impacted the degree of spatial overlap and hence the strength of
the predator-prey relationship between polar bears and ringed seals, with
consequences for the wider Arctic marine and terrestrial ecosystems. Shifts in
ecological interactions are likely to become more widespread in many ecosystems
as both predators and prey respond to changing environmental conditions induced
by global warming, highlighting the importance of multi-species studies.
PMID- 28415135
TI - The effects of enteral feeding improvement massage on premature infants: A
randomised controlled trial.
AB - AIMS AND OBJECTIVES: To prove the effects of an enteral feeding improvement
massage for premature infants with regard to their feeding, growing and superior
mesentery artery blood flow aspect by a randomised controlled trial. BACKGROUND:
Premature infants have feeding-related problems related to eating and absorbing
nutrition due to their immature gastrointestinal function. Studies regarding the
effectiveness of premature infants' enteral feeding improvement by tactile
stimulation massage are rare. DESIGN: The study group was composed of 55
patients. Of the 55 patients, 26 were randomised into an experimental group and
29 were randomised into a control group. METHODS: They were all born <34 weeks of
gestational age between 1 July 2011 and 30 March 2012. Premature infants in the
experimental group received enteral feeding improvement massage twice a day for
14 days, and infants in the control group received a sham exercise. The collected
data were analysed by spss 19.0, through t test, chi-square test (Fisher's exact)
and ANCOVA. RESULTS: (i) The experimental group had reached the day of full
enteral feeding significantly faster. (ii) The experimental group had a higher
superior mesentery artery peak velocity (Vmax ) and lower RI (resistant index).
(iii) The experimental group of the feeding-intolerant subgroup had a higher
superior mesentery artery Vmax and Vmin . (iv) The experimental group had a
heavier weight and larger head circumference after 14 days. CONCLUSIONS: This
study demonstrates that enteral feeding improvement massage can be helpful for
achieving earlier full enteral feeding, more increased superior mesentery artery,
and faster growing. In particular, it can be a therapeutic, independent and
evidence-based nursing intervention for feeding-intolerant premature infants.
RELEVANCE TO CLINICAL PRACTICE: Neonatal nurses in neonatal intensive care unit
can apply enteral feeding improvement massage massage for feeding-intolerant
infants.
PMID- 28415136
TI - Prevalence and descriptive epidemiology of atopic dermatitis and its impact on
quality of life in Singapore.
PMID- 28415137
TI - Drivers of species' role in avian seed-dispersal mutualistic networks.
AB - The mutualistic interaction between frugivore birds and the fruiting plants they
disperse presents an asymmetric interaction pattern, with some species having a
more important role (i.e. being essential) for maintaining the structure and
functioning of the interaction network. The identification of the biological
characteristics of these species is of major importance for the understanding and
conservation of seed-dispersal interactions. In this study, I use a network
approach and avian seed-dispersal networks from 23 different geographical areas
to test five hypotheses about species characteristics determining the structure
of the assemblage. I expected (i) large birds to forage on a large number of
fruits and (ii) large fruits to be dispersed by few bird species (because of
morphological constraints), and (iii) highly energetic fruits to be dispersed by
more bird species (in accordance with optimal foraging theory). Besides the
number of interacting partners, I also expected (iv) large birds and (v) small
energetic fruits to be important for the maintenance of the structure of the
interactions in seed-dispersal networks. As species that are closely related are
more likely to be similar to each other, I performed phylogenetically corrected
analyses to account for this data dependence. Although bird size was not
associated to species important in the maintenance of the structure of the seed
dispersal community, I identified that bird species whose diet was strongly
dependent on fruits were important for the structure of the network. Regarding
the plants, I found that large fruits were dispersed by fewer species, but the
most important attribute to predict the role of a fruit was its energy content
(higher energy, more bird species dispersing the plant, but low-energy fruits
being of conservation concern because they are dispersed by specific species).
The results of this study suggest that the role of the species in seed-dispersal
assemblages seems to be determined by the role of the species as consumers
(frugivory degree for animals) or by their nutritional inputs (energy content for
fruits) rather than by morphological constrains.
PMID- 28415139
TI - Primary nocturnal enuresis: Assessment and treatment at a single referral center.
AB - BACKGROUND: The aim of this study was to investigate the prevalence of primary
monosymptomatic and non-monosymptomatic nocturnal enuresis (PMNE and PNMNE) and
associated factors in a major referral center for NE in Abu Dhabi. METHODS:
Children referred to the Paediatric Continence Clinic, between 2014 and 2016, for
PNE were included in the study. Exclusion criteria were neuropathic bladder,
abnormality of the bladder and bowel, urethral stenosis, neurological and
psychiatric problems, non-completion of the diagnostic protocol, and follow up <6
months. RESULTS: A total of 128 patients were included in the study: 82 boys
(64.1%) and 46 girls (35.9%). A total of 42.7% of boys and 8.7% of girls had
PMNE, and 57.3% of boys and 91.3% of girls had PNMNE. Constipation was present in
46% of patients. In the male PNMNE group, 74.5% had overactive bladder (OAB),
10.6%, dysfunctional voiding (DV); and 14.9%, OAB + DV. In the female PNMNE
group, 35.7% had OAB; 21.4%, DV; 40.5%, OAB + DV; and 2.4%, underactive bladder.
A total of 97% and 86 of children with PMNE and PNMNE, respectively, had
resolution of NE. Boys had a significantly higher incidence of PMNE, and girls,
of DV. CONCLUSION: In Abu Dhabi, NE is often associated with bladder dysfunction
or DV, mostly in girls, and with constipation. High intake of dry, low fiber
foods, along with hot weather and the stress of city living negatively affect the
incidence of fecal retention and of NE. A multimodal approach, including the
treatment of constipation, led to a satisfactory resolution of PNE in almost 90%
of cases.
PMID- 28415140
TI - Imaging modalities for characterising focal pancreatic lesions.
AB - BACKGROUND: Increasing numbers of incidental pancreatic lesions are being
detected each year. Accurate characterisation of pancreatic lesions into benign,
precancerous, and cancer masses is crucial in deciding whether to use treatment
or surveillance. Distinguishing benign lesions from precancerous and cancerous
lesions can prevent patients from undergoing unnecessary major surgery. Despite
the importance of accurately classifying pancreatic lesions, there is no clear
algorithm for management of focal pancreatic lesions. OBJECTIVES: To determine
and compare the diagnostic accuracy of various imaging modalities in detecting
cancerous and precancerous lesions in people with focal pancreatic lesions.
SEARCH METHODS: We searched the CENTRAL, MEDLINE, Embase, and Science Citation
Index until 19 July 2016. We searched the references of included studies to
identify further studies. We did not restrict studies based on language or
publication status, or whether data were collected prospectively or
retrospectively. SELECTION CRITERIA: We planned to include studies reporting
cross-sectional information on the index test (CT (computed tomography), MRI
(magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic
ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle
aspiration)) and reference standard (confirmation of the nature of the lesion was
obtained by histopathological examination of the entire lesion by surgical
excision, or histopathological examination for confirmation of precancer or
cancer by biopsy and clinical follow-up of at least six months in people with
negative index tests) in people with pancreatic lesions irrespective of language
or publication status or whether the data were collected prospectively or
retrospectively. DATA COLLECTION AND ANALYSIS: Two review authors independently
searched the references to identify relevant studies and extracted the data. We
planned to use the bivariate analysis to calculate the summary sensitivity and
specificity with their 95% confidence intervals and the hierarchical summary
receiver operating characteristic (HSROC) to compare the tests and assess
heterogeneity, but used simpler models (such as univariate random-effects model
and univariate fixed-effect model) for combining studies when appropriate because
of the sparse data. We were unable to compare the diagnostic performance of the
tests using formal statistical methods because of sparse data. MAIN RESULTS: We
included 54 studies involving a total of 3,196 participants evaluating the
diagnostic accuracy of various index tests. In these 54 studies, eight different
target conditions were identified with different final diagnoses constituting
benign, precancerous, and cancerous lesions. None of the studies was of high
methodological quality. None of the comparisons in which single studies were
included was of sufficiently high methodological quality to warrant highlighting
of the results. For differentiation of cancerous lesions from benign or
precancerous lesions, we identified only one study per index test. The second
analysis, of studies differentiating cancerous versus benign lesions, provided
three tests in which meta-analysis could be performed. The sensitivities and
specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95%
confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00);
EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to
0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39
to 0.84). The third analysis, of studies differentiating precancerous or
cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which
meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing
precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and
high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence
intervals reflecting the heterogeneity between the studies). The fourth analysis,
of studies differentiating cancerous (invasive carcinoma) from precancerous
(dysplasia) provided three tests in which meta-analysis was performed. The
sensitivities and specificities for diagnosing invasive carcinoma were: CT:
sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97);
EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to
0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI
0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high
grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate
grade dysplasia) provided six tests in which meta-analysis was performed. The
sensitivities and specificities for diagnosing cancer (high-grade dysplasia or
invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity
0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92),
specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to
0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen
200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19
to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI
0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95%
CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous
(invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in
which meta-analysis was performed. The seventh analysis, of studies
differentiating precancerous or cancerous (intermediate- or high-grade dysplasia
or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests
in which meta-analysis was performed. The sensitivity and specificity for
diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity
0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92),
specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of
studies differentiating precancerous or cancerous (intermediate- or high-grade
dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or
benign lesions provided no test in which meta-analysis was performed.There were
no major alterations in the subgroup analysis of cystic pancreatic focal lesions
(42 studies; 2086 participants). None of the included studies evaluated EUS
elastography or sequential testing. AUTHORS' CONCLUSIONS: We were unable to
arrive at any firm conclusions because of the differences in the way that study
authors classified focal pancreatic lesions into cancerous, precancerous, and
benign lesions; the inclusion of few studies with wide confidence intervals for
each comparison; poor methodological quality in the studies; and heterogeneity in
the estimates within comparisons.
PMID- 28415138
TI - The roles of valuation and reward processing in cognitive function and
psychiatric disorders.
AB - In neuroeconomics, valuation refers to the process of assigning values to states
and actions on the basis of the animal's current representation of the
environment, while reward processing corresponds to processing the feedback
received from the environment to update the values of states and actions. In this
article, we review the brain circuits associated with valuation and reward
processing and argue that these are fundamental processes critical to many
cognitive functions. Specifically, we focus on the role of valuation and reward
processing in attention, memory, decision making, and learning. Next, the extant
neuroimaging literature on a number of psychiatric disorders is reviewed (i.e.,
addiction, pathological gambling, schizophrenia, and mood disorders), and an
argument is made that associated deficits in cognitive functions can be explained
in terms of abnormal valuation and reward processing. The review concludes with
the impact of this framework in clinical settings and prescriptions for future
research, in particular with regard to the conversions of qualitatively different
valuation systems into a system of common currency.
PMID- 28415141
TI - Claudin-targeted drug development using anti-claudin monoclonal antibodies to
treat hepatitis and cancer.
AB - The 27-member family of tetraspan membrane proteins known as claudins (CLDNs) is
a major component of tight junctions. A series of studies elucidating the
relationship between CLDNs and various pathological conditions has provided new
insights into drug development. For instance, CLDN-1 may be a potent target for
epidermal absorption of drugs and for treating hepatitis C virus (HCV) infection.
CLDN-4 may be a target for treating cancer. Because CLDNs are also expressed in
various normal tissues, safety and efficacy evaluations are critical for
translational research. We previously developed several anti-CLDN antibodies and
have established proof of concept for CLDN-targeted drug development using these
reagents. Here, we provide an overview of CLDN-1 as a target for improving
epidermal drug absorption and preventing HCV infection and of CLDN-4 as a target
for anticancer therapeutics.
PMID- 28415144
TI - Build the network.
PMID- 28415143
TI - Cardiorespiratory fitness and health-related quality of life in women at risk for
gestational diabetes.
AB - This study examined the associations of cardiorespiratory fitness (CRF) and
leisure-time physical activity (LTPA) with health-related quality of life (HRQoL)
in women at risk for gestational diabetes mellitus (GDM). The participants were
39 women planning pregnancy with a history of GDM and/or BMI >29 kg/m2 . We
assessed CRF by measuring maximal oxygen consumption (VO2max ) during incremental
cycle ergometer exercise until voluntary fatigue. LTPA was self-reported, and
HRQoL assessed with the SF-36 Health Survey (SF-36). The mean (SD) VO2max was 27
(6) mL.kg-1 .min-1 , and the mean LTPA was 2.6 (1.7) h/wk. After controlling for
BMI, VO2max was positively associated with the SF-36 General Health scale (beta
1.27, 95% CI: 0.09, 2.44, P=.035) and the Physical Component Summary (beta 0.48,
95% CI: 0.14, 0.82, P=.007). The General Health scale (P=.023) and the Physical
Component Summary (P=.011) differed even between those with very poor and poor
CRF. After controlling for BMI, LTPA was positively associated with the SF-36
Physical Functioning scale (rs =.34, P=.039), the General Health scale (beta
3.74, 95% CI: 0.64, 6.84, P=.020), and the Physical Component Summary (beta 1.13
95% CI: 0.19, 2.06, P=.020). To conclude, CRF and LTPA were positively associated
with perceived general health and physical well-being in women planning pregnancy
and at risk for GDM. Even a slightly better CRF would be beneficial for well
being among women with low levels of CRF.
PMID- 28415145
TI - Medical marijuana: Challenges and risk issues for health care providers.
AB - Laws on medical marijuana and recreational use of marijuana are sweeping the
country and presenting real dilemmas for health care providers and facilities.
However, due to disagreements between federal and state law, there are no easy
answers. Additionally, the case law and statutory law on these issues is
exceedingly sparse. It may take years for all of the issues to be ironed out, but
health care facilities will need to act in the meantime on what may be little
more than educated guesses. It may not be appropriate to simply prohibit the use
of medical marijuana, but accommodating it also has risk. This article will
address what is known about the subject and what is not known about the subject.
Each provider and health care facility will need to devise their own approach to
the subject based on principles that are presently known, while keeping an eye on
the health and safety of all involved.
PMID- 28415146
TI - A time of uncertainty, a time to step forward.
PMID- 28415142
TI - Neural correlates of cognitive processing in monolinguals and bilinguals.
AB - Here, we review the neural correlates of cognitive control associated with
bilingualism. We demonstrate that lifelong practice managing two languages
orchestrates global changes to both the structure and function of the brain.
Compared with monolinguals, bilinguals generally show greater gray matter volume,
especially in perceptual/motor regions, greater white matter integrity, and
greater functional connectivity between gray matter regions. These changes
complement electroencephalography findings showing that bilinguals devote neural
resources earlier than monolinguals. Parallel functional findings emerge from the
functional magnetic resonance imaging literature: bilinguals show reduced frontal
activity, suggesting that they do not need to rely on top-down mechanisms to the
same extent as monolinguals. This shift for bilinguals to rely more on
subcortical/posterior regions, which we term the bilingual anterior-to-posterior
and subcortical shift (BAPSS), fits with results from cognitive aging studies and
helps to explain why bilinguals experience cognitive decline at later stages of
development than monolinguals.
PMID- 28415147
TI - Neurosurgical laser ablation and MR thermometry: Risks of multisite workflow
pattern.
AB - Neurosurgical laser ablation is a relatively new but rapidly growing application
of stereotactic neurosurgery that allows neurosurgeons to treat many previously
untreatable conditions with the added benefit of shorter hospitalizations and
recovery times. The vast majority of these procedures, however, are performed
using a multisite workflow pattern involving transport of the patient between the
operating room (OR), the computed tomography (CT) suite, and the magnetic
resonance imaging (MRI) suite, often necessitating patient transfer through
public pathways and requiring multiple trips if laser fiber placement is not
accurate. There are significant risks posed to the patient with this practice and
no existing guidelines addressing it. This article serves to identify those risks
and present recommendations for safety optimization and risk reduction for those
health care facilities using a multisite workflow pattern.
PMID- 28415148
TI - The "6 A's": A risk manager's guide to emergency cesarean delivery.
AB - The allegation of delay in performing an emergency cesarean delivery is common in
litigation involving neurological injury to newborns. Analyzing the actual
performance of an emergency cesarean involves multiple steps, individuals, and
systemic processes that need coordination for appropriate action when necessary.
This article gives risk managers a systematic way to evaluate a given perinatal
unit's approach to the ability to perform an emergency cesarean through
evaluating the 6 "A"s: Assess, Alert, Align, Assemble, Act, and Analyze. Each of
these elements is discussed based on current evidence. A checklist that may be
useful in the evaluation of the elements of performance of emergency cesarean
delivery is provided.
PMID- 28415149
TI - Integrating TeamSTEPPS(r) into ambulatory reproductive health care: Early
successes and lessons learned.
AB - BACKGROUND: Most medical teamwork improvement interventions have occurred in
hospitals, and more efforts are needed to integrate them into ambulatory care
settings. In 2014, Affiliates Risk Management Services, Inc. (ARMS), the risk
management services organization for a large network of reproductive health care
organizations in the United States, launched a voluntary 5-year initiative to
implement a medical teamwork system in this network using the TeamSTEPPS model.
This article describes the ARMS initiative and progress made during the first 2
years, including lessons learned. METHODS: The ARMS TeamSTEPPS program consists
of the following components: preparation of participating organizations,
TeamSTEPPS master training, implementation of teamwork improvement programs, and
evaluation. We used self-administered questionnaires to assess satisfaction with
the ARMS program and with the master training course. RESULTS: In the first 2
years, 20 organizations enrolled. Participants found the preparation phase
valuable and were highly satisfied with the master training course. Although most
attendees felt that the course imparted the knowledge and tools critical for
TeamSTEPPS implementation, they identified time restraints and competing
initiatives as potential barriers. The project team has learned valuable lessons
about obtaining buy-in, consolidating the change teams, making the curriculum
relevant, and evaluation. CONCLUSION: Ambulatory care settings require innovative
approaches to integration of teamwork improvement systems. Evaluating and sharing
lessons learned will help to hone best practices as we navigate this new frontier
in the field of patient safety.
PMID- 28415150
TI - Case law update.
PMID- 28415151
TI - Correction.
PMID- 28415152
TI - Oral Candida colonization and oral lichen planus.
PMID- 28415153
TI - Polar and charged extracellular residues conserved among barrier-forming claudins
contribute to tight junction strand formation.
AB - Claudins (Cldn) form the backbone of tight junction (TJ) strands and thereby
regulate paracellular permeability for solutes and water. Polymeric strands are
formed by homo- and heterophilic cis- and trans-interactions between claudin
protomers. Crystal structures of some claudins have been resolved; however, the
mechanism by which claudins assemble into TJ strands remains unclear. To
elucidate strand architecture, TJ-like strands were reconstituted in HEK293 cells
by claudin transfection. Determinants of prototypic, classic barrier-forming
claudins (Cldn1, -3, and -5) involved in strand formation were analyzed by
mutagenesis. The capability of claudin constructs to interact in trans and to
form strands was investigated by cell contact-enrichment assays and freeze
fracture electron microscopy. Residues in extracellular loops 1 and 2 of the
claudins affecting strand formation were identified. Using homology modeling and
molecular docking, we tested working concepts for the arrangement of claudin
protomers within TJ strands. We show that the charge of Lys65 in Cldn1 and Glu158
in Cldn3, but not of Arg30 or Asp145 in Cldn3, and the polarity of Gln56 and
Gln62 in Cldn3 and of Gln57 in Cldn5 are necessary for TJ strand formation. These
residues are all conserved among barrier-forming classic claudins. The results
contribute to mechanistic understanding of claudin-based regulation of
paracellular permeability.
PMID- 28415154
TI - Annona species (Annonaceae): a rich source of potential antitumor agents?
AB - Plants have provided the basis of traditional medicine systems throughout the
world for thousands of years and continue to yield molecules for new remedies. We
analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae),
including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa,
A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here,
we report and discuss the mechanisms of action and structure-activity
relationships of the most active Annona constituents. Annonaceous acetogenins are
one of the most promising classes of natural products, owing to their potential
antitumor activity. However, their neurotoxicity should not be underestimated.
PMID- 28415155
TI - Letter to the Editor regarding Dounousi E et al. Intact FGF23 and alpha-Klotho
during acute inflammation/sepsis in CKD patients.
PMID- 28415157
TI - A Small Case Series of Intravascular Large B-Cell Lymphoma with Unexpected
Findings: Subset of Cases with Concomitant Extravascular Central Nervous System
(CNS) Involvement Mimicking Primary CNS Lymphoma.
AB - BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of
extranodal lymphoma with growth mainly in the lumina of vessels. We studied a
small series of IVLBCL and focused on its central nervous system (CNS)
involvement. METHODS: Searching the medical records of Northwestern Memorial
Hospital, we identified five cases of IVLBCL from January 2007 to January 2015.
Clinical information, hematoxylin and eosin stained histologic slides and
immunohistochemistry studies were reviewed for all cases. Polymerase chain
reaction (PCR) analysis for the immunoglobulin (Ig) heavy and light chain gene
rearrangement was performed on all five cases. RESULTS: Three of the five cases
of IVLBCL were autopsies. Patients' age ranged from 56 to 84. CNS involvement was
present in two cases-in both patients, the CNS involvement showed an
extravascular pattern with confluent sheet-like formation. PCR analysis confirmed
that in one case the systemic intravascular and CNS extravascular components were
clonally identical. CONCLUSIONS: In a small case series of IVLBCL, we observed
that CNS involvement by IVLBCL often has an extravascular morphology, but is
clonally identical to the intravascular counterpart by PCR analysis. As IVLBCL
can have a rapidly progressing poor outcome, it should be kept in the
differential diagnoses for patients presenting with lymphoma of the CNS. The
presence of extravascular growth patterns in the CNS should not exclude IVLBCL as
a diagnosis.
PMID- 28415158
TI - Clinicopathological Study of 18 Cases of Inflammatory Myofibroblastic Tumors with
Reference to ALK-1 Expression: 5-Year Experience in a Tertiary Care Center.
AB - BACKGROUND: Inflammatory myofibroblastic tumor is a histopathologically
distinctive neoplasm of children and young adults. According to World Health
Organization (WHO) classification, inflammatory myofibroblastic tumor is an
intermediate-grade tumor, with potential for recurrence and rare metastasis.
There are no definite histopathologic, molecular, or cytogenetic features to
predict malignant transformation, recurrence, or metastasis. METHODS: A 5-year
retrospective study of histopathologically diagnosed inflammatory myofibroblastic
tumors of various anatomic sites was conducted to correlate anaplastic lymphoma
kinase-1 (ALK-1) expression with histological atypia, multicentric origin of
tumor, recurrence, and metastasis. Clinical details of all the cases were noted
from the clinical work station. Immunohistochemical stains for ALK-1 and other
antibodies were performed. Statistical analysis was done using Fisher exact test.
RESULTS: A total of 18 cases of inflammatory myofibroblastic tumors were found
during the study period, of which 14 were classical. The female-male ratio was
1:1 and the mean age was 23.8 years. Histologically atypical (four cases) and
multifocal tumors (three cases, multicentric in origin) were noted. Recurrence
was noted in 30% of ALK-1 positive and 37.5% of ALK-1 negative cases, whereas
metastasis to the lung, liver, and pelvic bone was noted in the ALK-1 positive
group only. CONCLUSIONS: Overall, ALK-1 protein was expressed in 55.6% of
inflammatory myofibroblastic tumors. There was no statistically significant
correlation between ALK-1 expression, tumor type, recurrence and metastasis.
However, ALK-1 immunohistochemistry is a useful diagnostic aid in the appropriate
clinical and histomorphologic context.
PMID- 28415156
TI - Endocytosis of tight junction proteins and the regulation of degradation and
recycling.
AB - Internalization of tight junction (TJ) proteins from the plasma membrane is a
pivotal mechanism regulating TJ plasticity and function in both epithelial and
endothelial barrier tissues. Once internalized, the TJ proteins enter complex
vesicular machinery, where further trafficking is directly dependent on the
initiating stimulus and downstream signaling pathways that regulate the sorting
and destiny of TJ proteins, as well as on cell and barrier responses. The destiny
of internalized TJ proteins is recycling to the plasma membrane or sorting to
late endosomes and degradation. This review highlights recent advances in our
knowledge of endocytosis and vesicular trafficking of TJ proteins in both
epithelial and endothelial cells. A greater understanding of these processes may
allow for the development of methods to modulate barrier permeability for drug
delivery or prevent barrier dysfunction in disease states.
PMID- 28415159
TI - Comparison of Unsatisfactory Samples from Conventional Smear versus Liquid-Based
Cytology in Uterine Cervical Cancer Screening Test.
AB - BACKGROUND: Cervical cytology for uterine cervical cancer screening has
transitioned from conventional smear (CS) to liquid-based cytology (LBC), which
has many advantages. The aim of this study was to compare the proportion of
unsatisfactory specimens from CS versus LBC at multiple institutions including
general hospitals and commercial laboratories. METHODS: Each participating
institution provided a minimum of 500 Papanicolaou (Pap) test results for
analysis. Pap tests were classified according to the participating institution
(commercial laboratory or general hospital) and the processing method (CS,
ThinPrep, SurePath, or CellPrep). The causes of unsatisfactory results were
classified as technical problems, scant cellularity, or complete obscuring
factors. RESULTS: A total of 38,956 Pap test results from eight general hospitals
and three commercial laboratories were analyzed. The mean unsatisfactory rate of
LBC was significantly lower than that of CS (1.26% and 3.31%, p = .018). In the
LBC method, samples from general hospitals had lower unsatisfactory rates than
those from commercial laboratories (0.65% vs 2.89%, p = .006). The reasons for
unsatisfactory results were heterogeneous in CS. On the other hand, 66.2% of
unsatisfactory results in LBC were due to the scant cellularity. CONCLUSIONS:
Unsatisfactory rate of cervical cancer screening test results varies according to
the institution and the processing method. LBC has a significantly lower
unsatisfactory rate than CS.
PMID- 28415160
TI - A first case of high-flow nasal cannula oxygen therapy in patients with pulmonary
tumor thrombotic microangiopathy.
PMID- 28415161
TI - Lymphoid follicular proctitis resembling rectal carcinoid tumor, confirmed by
endoscopic resection.
PMID- 28415162
TI - Value of Doppler evaluation of physically abnormal fistula: hemodynamic
guidelines and access outcomes.
AB - Background/Aims: The strategy of access care at out center involves the use of
ultrasound (USG) in case of physical examination (PE) abnormality. USG determines
the need of angiography. This study investigated the possible association between
the need for percutaneous transluminal angioplasty (PTA) and hemodynamic
parameters of USG. The study also assessed the effects of this monitoring
strategy on outcomes in comparison with a historical control. Methods: A
retrospective study of the medical records of 127 patients (65 PTA, 62 non-PTA)
was conducted. Data were analyzed using logistic regression analysis and receiver
operating characteristic curve. Fistula outcomes and intervention rates were
calculated and compared with 100 historic controls. Results: Logistic regression
analysis showed that brachial artery flow volume (FV) < 612.9 mL/min or brachial
artery resistance index (RI) > 0.63 was independently associated with the need
for PTA. This monitoring strategy showed an a reduction in thromboses (0.02 +/-
0.11 events/arteriovenous fistula [AVF]-year vs. 0.07 +/- 0.23 events/AVF-year, p
= 0.046), reduction in central venous catheter placement (0.01 +/- 0.05
events/AVF-year vs. 0.06 +/- 0.22 events/AVF-year, p = 0.010), reduction in
access loss (0.02 +/- 0.13 events/AVF-year vs. 0.19 +/- 0.34 events/AVF-year, p =
0.015), and increase in access selective repair (0.49 +/- 0.66 events/AVF-year
vs. 0.21 +/- 0.69 events/AVF-year, p = 0.003), compared to historic control.
Conclusions: There was significant stenosis if brachial artery FV was < 612.9
mL/min or RI was > 0.63 for PE abnormality. These parameters should be used as
markers for assessing PTA risk in hemodialysis patients. Addition of USG to
determine the need of angiography after detection of PE abnormality leads to
decreases in access thrombosis, catheter placement, and access loss despite
increasing access intervention rates compared to clinical monitoring.
PMID- 28415164
TI - Beyond the Classic Segawa Disease, GCH1-Associated Neurodegenerative
Parkinsonism: Practical Considerations for Physicians.
PMID- 28415163
TI - Fragmented QRS and abnormal creatine kinase-MB are predictors of coronary artery
disease in patients with angina and normal electrocardiographys.
AB - BACKGROUND/AIMS: Patients with symptoms of coronary artery disease (CAD) often
display normal tracings or only nonspecific changes on electrocardiography (ECG).
The aim of this study was to explore strategic elements of the ECG and other
potential factors that are predictive of CAD in this scenario. METHODS: This was
an observational study of 142 patients with the chief complaint of chest pain,
each of whom presented with a normal ECG and was subjected to emergency coronary
angiography (CAG). Two population subsets were identified: those patients (n =
97) with no significant stenotic lesions and those (n = 45) with the significant
stenotic lesions of CAD. RESULTS: Those patients with normal or nonspecific ECGs
and CAD (15.8%) were more likely to have left circumflex artery involvement (20%
vs. 7%). In patients with normal ECGs and CAD (vs. normal CAG), male sex (86.7%
vs. 68%, p = 0.023), creatine kinase-MB (CK-MB) levels > 10 U/L (13 vs. 10, p =
0.025), and fragmented QRS (fQRS) (38.6% vs. 21.6%, p = 0.042) occurred with
greater frequency. In multivariable analysis, the following variables were
significant predictors of CAD, given a normal ECG: male sex (odds ratio [OR],
2.593; 95% confidence interval [CI], 1.068 to 5.839); CK-MB (OR, 2.497; 95% CI,
0.955 to 7.039); and W- or M-shaped QRS complex (OR, 2.306; 95% CI 0.988 to
5.382). CONCLUSIONS: In our view, male sex, elevated CK-MB (> 10 U/L), and fQRS
complexes are suspects for CAD in patients with angina and unremarkable ECGs and
should be considered screening tests.
PMID- 28415165
TI - Progressive Supranuclear Gaze Palsy with Predominant Cerebellar Ataxia: A Case
Series with Videos.
AB - Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C)
is a rare phenotype of PSP. The clinical and radiological features of this
disorder remain poorly characterized. Through a retrospective case series, we aim
to characterize the clinical and radiological features of PSP-C. Four patients
with PSP-C were identified: patients who presented with prominent cerebellar
dysfunction that disappeared with the progression of the disease. Supranuclear
gaze palsy occurred at a mean of 2.0 +/- 2.3 years after the onset of ataxia.
Mild cerebellar volume loss and midbrain atrophy were detected on brain imaging,
which are supportive of a diagnosis of PSP. Videos are presented illustrating the
co-existence of cerebellar signs and supranuclear gaze palsy and the
disappearance of cerebellar signs with disease progression. Better recognition
and the development of validated diagnostic criteria would aid in the antemortem
recognition of this rare condition.
PMID- 28415166
TI - Holmes' Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral
Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus.
AB - A 21-year-old male was admitted with severe right arm and hand tremors after a
thalamic hemorrhage caused by a traffic accident. He was also suffering from
agonizing pain in his right shoulder that manifested after the tremor. Neurologic
examination revealed a disabling, severe, and irregular kinetic and postural
tremor in the right arm during target-directed movements. There was also an
irregular ipsilateral rest tremor and dystonic movements in the distal part of
the right arm. The amplitude was moderate at rest and extremely high during
kinetic and intentional movements. The patient underwent left globus pallidum
internus and ventral intermediate thalamic nucleus deep brain stimulation. The
patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating
Scale and Visual Analog Scale six months after surgery.
PMID- 28415167
TI - There Is No Advantage to Transpapillary Pancreatic Duct Stenting for the
Transmural Endoscopic Drainage of Pancreatic Fluid Collections: A Meta-Analysis.
AB - BACKGROUND/AIMS: Options for the endoscopic management of symptomatic pancreatic
fluid collections (PFCs) include transmural drainage (TM) alone, transpapillary
drainage (TP) alone, or a combination of both drainage method (CD). There have
been conflicting reports about the best method. This study performed a meta
analysis to determine whether CD presents an added clinical benefit over TM.
METHODS: The included studies compared TM with CD and reported clinical success
for both methods. A random-effects model was used to determine the pooled odds
ratios (ORs) and the 95% confidence intervals (CIs) for the following outcomes:
technical success, clinical success, complications, and recurrence. RESULTS: Nine
studies involving a combined total of 604 drainage procedures-373 TMs (62%) and
231 CDs (38%)-were included. CD showed no additional benefit over TM in terms of
technical success (OR, 1.12; 95% CI, 0.37-3.37; p=0.85), clinical success (OR,
1.11; 95% CI, 0.65-1.89; p=0.70), recurrence (OR, 1.49; 95% CI, 0.53-4.21;
p=0.45), or complications (OR, 1.15; 95% CI, 0.61-2.18; p=0.67). CONCLUSIONS:
Pancreatic duct (PD) stenting provides no additional clinical benefit for the TM
of PFCs (particularly pseudocysts). Patients undergoing the TM of symptomatic
pseudocysts may not require endoscopic retrograde pancreatography (ERP).
PMID- 28415168
TI - An Update on Endoscopic Management of Post-Liver Transplant Biliary
Complications.
AB - Biliary complications are the most common post-liver transplant (LT)
complications with an incidence of 15%-45%. Furthermore, such complications are
reported more frequently in patients who undergo a living-donor LT compared to a
deceased-donor LT. Most post-LT biliary complications involve biliary strictures,
bile leakage, and biliary stones, although many rarer events, such as hemobilia
and foreign bodies, contribute to a long list of related conditions. Endoscopic
treatment of post-LT biliary complications has evolved rapidly, with new and
effective tools improving both outcomes and success rates; in fact, the latter
now consistently reach up to 80%. In this regard, conventional endoscopic
retrograde cholangiopancreatography remains the preferred initial treatment.
However, percutaneous transhepatic cholangioscopy is now central to the
management of endoscopy-resistant cases involving complex hilar or multiple
strictures with associated stones. Many additional endoscopic tools and
techniques-such as the rendezvous method, magnetic compression anastomosis , and
peroral cholangioscopy-combined with modified biliary stents have significantly
improved the success rate of endoscopic management. Here, we review the current
status of endoscopic treatment of post-LT biliary complications and discuss
conventional as well as the aforementioned new tools and techniques.
PMID- 28415169
TI - Understanding the origin of liquid crystal ordering of ultrashort double-stranded
DNA.
AB - Recent experiments have shown that short double-stranded DNA (dsDNA) fragments
having six- to 20-base pairs exhibit various liquid crystalline phases. This
violates the condition of minimum molecular shape anisotropy that analytical
theories demand for liquid crystalline ordering. It has been hypothesized that
the liquid crystalline ordering is the result of end-to-end stacking of dsDNA to
form long supramolecular columns which satisfy the shape anisotropy criterion
necessary for ordering. To probe the thermodynamic feasibility of this process,
we perform molecular dynamics simulations on ultrashort (four base pair long)
dsDNA fragments, quantify the strong end-to-end attraction between them, and
demonstrate that the nematic ordering of the self-assembled stacked columns is
retained for a large range of temperature and salt concentration.
PMID- 28415170
TI - Variational calculation of transport coefficients in diffusive lattice gases.
AB - A diffusive lattice gas is characterized by the diffusion coefficient depending
only on the density. The Green-Kubo formula for diffusivity can be represented as
a variational formula, but even when the equilibrium properties of a lattice gas
are analytically known, the diffusion coefficient can be computed only in the
exceptional situation when the lattice gas is gradient. In the general case,
minimization over an infinite-dimensional space is required. We propose an
approximation scheme based on minimizing over finite-dimensional subspaces of
functions. The procedure is demonstrated for one-dimensional generalized
exclusion processes in which each site can accommodate at most two particles. Our
analytical predictions provide upper bounds for the diffusivity that are very
close to simulation results throughout the entire density range. We also analyze
nonequilibrium density profiles for finite chains coupled to reservoirs. The
predictions for the profiles are in excellent agreement with simulations.
PMID- 28415171
TI - Acousto-optic effect in random media.
AB - We consider the acousto-optic effect in a random medium. We derive the radiative
transport equations that describe the propagation of multiply scattered light in
a medium whose dielectric permittivity is modulated by an acoustic wave. Using
this result, we present an analysis of the sensitivity of an acousto-optic
measurement to the presence of a small absorbing inhomogeneity.
PMID- 28415172
TI - Averaged model for probabilistic coalescence avalanches in two-dimensional
emulsions: Insights into uncertainty propagation.
AB - A two-dimensional concentrated emulsion exhibits spontaneous rapid
destabilization through an avalanche of coalescence events which propagate
through the assembly stochastically. We propose a deterministic model to explain
the average dynamics of the avalanching process. The dynamics of the avalanche
phenomenon is studied as a function of a composite parameter, the decay time
ratio, which characterizes the ratio of the propensity of coalescence to cease
propagation to that of propagation. When this ratio is small, the avalanche grows
autocatalytically to destabilize the emulsion. Using a scaling analysis, we
unravel the relation between a local characteristic of the system and a global
system wide effect. The anisotropic nature of local coalescence results in a
system size dependent transition from nonautocatalytic to autocatalytic behavior.
By incorporating uncertainty into the parameters in the model, several possible
realizations of the coalescence avalanche are generated. The results are compared
with the Monte Carlo simulations to derive insights into how the uncertainty
propagates in the system.
PMID- 28415173
TI - Signal optimization in urban transport: A totally asymmetric simple exclusion
process with traffic lights.
AB - We consider the exclusion process on a ring with time-dependent defective bonds
at which the hopping rate periodically switches between zero and one. This system
models main roads in city traffics, intersecting with perpendicular streets. We
explore basic properties of the system, in particular dependence of the vehicular
flow on the parameters of signalization as well as the system size and the car
density. We investigate various types of the spatial distribution of the
vehicular density, and show existence of a shock profile. We also measure waiting
time behind traffic lights, and examine its relationship with the traffic flow.
PMID- 28415174
TI - Structure of the optimal path to a fluctuation.
AB - Macroscopic fluctuations have become an essential tool to understand physics far
from equilibrium due to the link between their statistics and nonequilibrium
ensembles. The optimal path leading to a fluctuation encodes key information on
this problem, shedding light on, e.g., the physics behind the enhanced
probability of rare events out of equilibrium, the possibility of dynamic phase
transitions, and new symmetries. This makes the understanding of the properties
of these optimal paths a central issue. Here we derive a fundamental relation
which strongly constrains the architecture of these optimal paths for general d
dimensional nonequilibrium diffusive systems, and implies a nontrivial structure
for the dominant current vector fields. Interestingly, this general relation
(which encompasses and explains previous results) makes manifest the
spatiotemporal nonlocality of the current statistics and the associated optimal
trajectories.
PMID- 28415175
TI - Yielding transitions and grain-size effects in dislocation theory.
AB - The statistical-thermodynamic dislocation theory developed in previous papers is
used here in an analysis of yielding transitions and grain-size effects in
polycrystalline solids. Calculations are based on the 1995 experimental results
of Meyers, Andrade, and Chokshi [Metall. Mater. Trans. A 26, 2881
(1995)MMTAEB1073-562310.1007/BF02669646] for polycrystalline copper under strain
hardening conditions. The main assertion is that the well-known Hall-Petch
effects are caused by enhanced strengths of dislocation sources at the edges of
grains instead of the commonly assumed resistance to dislocation flow across
grain boundaries. The theory describes rapid transitions between elastic and
plastic deformation at yield points; thus it can be used to predict grain-size
dependence of both yield stresses and flow stresses.
PMID- 28415176
TI - Multifractal surrogate-data generation algorithm that preserves pointwise Holder
regularity structure, with initial applications to turbulence.
AB - An algorithm is described that can generate random variants of a time series
while preserving the probability distribution of original values and the
pointwise Holder regularity. Thus, it preserves the multifractal properties of
the data. Our algorithm is similar in principle to well-known algorithms based on
the preservation of the Fourier amplitude spectrum and original values of a time
series. However, it is underpinned by a dual-tree complex wavelet transform
rather than a Fourier transform. Our method, which we term the iterated amplitude
adjusted wavelet transform can be used to generate bootstrapped versions of
multifractal data, and because it preserves the pointwise Holder regularity but
not the local Holder regularity, it can be used to test hypotheses concerning the
presence of oscillating singularities in a time series, an important feature of
turbulence and econophysics data. Because the locations of the data values are
randomized with respect to the multifractal structure, hypotheses about their
mutual coupling can be tested, which is important for the velocity-intermittency
structure of turbulence and self-regulating processes.
PMID- 28415177
TI - Influence of atomic kinetics in the simulation of plasma microscopic properties
and thermal instabilities for radiative bow shock experiments.
AB - Numerical simulations of laboratory astrophysics experiments on plasma flows
require plasma microscopic properties that are obtained by means of an atomic
kinetic model. This fact implies a careful choice of the most suitable model for
the experiment under analysis. Otherwise, the calculations could lead to
inaccurate results and inappropriate conclusions. First, a study of the validity
of the local thermodynamic equilibrium in the calculation of the average
ionization, mean radiative properties, and cooling times of argon plasmas in a
range of plasma conditions of interest in laboratory astrophysics experiments on
radiative shocks is performed in this work. In the second part, we have made an
analysis of the influence of the atomic kinetic model used to calculate plasma
microscopic properties of experiments carried out on magpie on radiative bow
shocks propagating in argon. The models considered were developed assuming both
local and nonlocal thermodynamic equilibrium and, for the latter situation, we
have considered in the kinetic model different effects such as external radiation
field and plasma mixture. The microscopic properties studied were the average
ionization, the charge state distributions, the monochromatic opacities and
emissivities, the Planck mean opacity, and the radiative power loss. The
microscopic study was made as a postprocess of a radiative-hydrodynamic
simulation of the experiment. We have also performed a theoretical analysis of
the influence of these atomic kinetic models in the criteria for the onset
possibility of thermal instabilities due to radiative cooling in those
experiments in which small structures were experimentally observed in the bow
shock that could be due to this kind of instability.
PMID- 28415178
TI - Capillary and geometrically driven fingering instability in nonflat Hele-Shaw
cells.
AB - The usual viscous fingering instability arises when a fluid displaces another of
higher viscosity in a flat Hele-Shaw cell, under sufficiently large capillary
number conditions. In this traditional framing, the reverse flow case (more
viscous fluid displacing a less viscous one) and the viscosity-matched situation
(fluids of equal viscosities) are stable. We revisit this classical fluid dynamic
problem, now considering flow in a nonflat Hele-Shaw cell. For a specific nonflat
environment, we show that both the reverse and the viscosity-matched flows can
become unstable, even at low capillary number. This peculiar fluid fingering
instability is driven by the combined action of capillary effects and geometric
properties of the nonflat Hele-Shaw cell. Our theoretical results indicate that
the Hele-Shaw cell geometry significantly impacts the linear stability and
nonlinear pattern-forming dynamics of the system. This suggests that the geometry
of the medium plays an important role in favoring the occurrence of fingering
patterns in nonflat, confined fluid flows.
PMID- 28415179
TI - Bias cancellation in one-determinant fixed-node diffusion Monte Carlo: Insights
from fermionic occupation numbers.
AB - The accuracy of the fixed-node diffusion Monte Carlo (FNDMC) depends on the node
location of the supplied trial state Psi_{T}. The practical FNDMC approaches
available for large systems rely on compact yet effective Psi_{T}, most often
containing an explicitly correlated single Slater determinant (SD). However, SD
nodes may be better suited to one system than to another, which may possibly lead
to inaccurate FNDMC energy differences. It remains a challenge how to estimate
nonequivalence or appropriateness of SDs. Here we use the differences of a
measure based on the Euclidean distance between the natural orbital occupation
number (NOON) vector of the SD and the exact solution in the NOON vector space,
which can be viewed as a measure of SD nonequivalence and as a qualitative
measure of the expected degree of nondynamic-correlation-related bias in FNDMC
energy differences. This is explored on a set of small noncovalent complexes and
covalent bond breaking of Si_{2} vs N_{2}. It turns out that NOON-based measures
well reflect the magnitude and sign of the bias present in the data available,
thus providing insights into the nature of bias cancellation in SD FNDMC energy
differences.
PMID- 28415181
TI - Universal data-based method for reconstructing complex networks with binary-state
dynamics.
AB - To understand, predict, and control complex networked systems, a prerequisite is
to reconstruct the network structure from observable data. Despite recent
progress in network reconstruction, binary-state dynamics that are ubiquitous in
nature, technology, and society still present an outstanding challenge in this
field. Here we offer a framework for reconstructing complex networks with binary
state dynamics by developing a universal data-based linearization approach that
is applicable to systems with linear, nonlinear, discontinuous, or stochastic
dynamics governed by monotonic functions. The linearization procedure enables us
to convert the network reconstruction into a sparse signal reconstruction problem
that can be resolved through convex optimization. We demonstrate generally high
reconstruction accuracy for a number of complex networks associated with distinct
binary-state dynamics from using binary data contaminated by noise and missing
data. Our framework is completely data driven, efficient, and robust, and does
not require any a priori knowledge about the detailed dynamical process on the
network. The framework represents a general paradigm for reconstructing,
understanding, and exploiting complex networked systems with binary-state
dynamics.
PMID- 28415180
TI - Reversals and collisions optimize protein exchange in bacterial swarms.
AB - Swarming groups of bacteria coordinate their behavior by self-organizing as a
population to move over surfaces in search of nutrients and optimal niches for
colonization. Many open questions remain about the cues used by swarming bacteria
to achieve this self-organization. While chemical cue signaling known as quorum
sensing is well-described, swarming bacteria often act and coordinate on time
scales that could not be achieved via these extracellular quorum sensing cues.
Here, cell-cell contact-dependent protein exchange is explored as a mechanism of
intercellular signaling for the bacterium Myxococcus xanthus. A detailed
biologically calibrated computational model is used to study how M. xanthus
optimizes the connection rate between cells and maximizes the spread of an
extracellular protein within the population. The maximum rate of protein
spreading is observed for cells that reverse direction optimally for swarming.
Cells that reverse too slowly or too fast fail to spread extracellular protein
efficiently. In particular, a specific range of cell reversal frequencies was
observed to maximize the cell-cell connection rate and minimize the time of
protein spreading. Furthermore, our findings suggest that predesigned motion
reversal can be employed to enhance the collective behavior of biological
synthetic active systems.
PMID- 28415182
TI - Sustained turbulence and magnetic energy in nonrotating shear flows.
AB - From numerical simulations, we show that nonrotating magnetohydrodynamic shear
flows are unstable to finite amplitude velocity perturbations and become
turbulent, leading to the growth and sustenance of magnetic energy, including
large scale fields. This supports the concept that sustained magnetic energy from
turbulence is independent of the driving mechanism for large enough magnetic
Reynolds numbers.
PMID- 28415183
TI - Fluctuations in Hertz chains at equilibrium.
AB - We examine the long-term behavior of nonintegrable, energy-conserved, one
dimensional systems of macroscopic grains interacting via a contact-only
generalized Hertz potential and held between stationary walls. Such systems can
be set up to have no phononic background excitation and represent examples of a
sonic vacuum. Existing dynamical studies showed the absence of energy
equipartitioning in such systems, hence their long-term dynamics was described as
quasiequilibrium. Here we show that these systems do in fact reach thermal
equilibrium at sufficiently long times, as indicated by the calculated heat
capacity. As a by-product, we show how fluctuations of system quantities, and
thus the distribution functions, are influenced by the Hertz potential. In
particular, the variance of the system's kinetic energy probability density
function is reduced by a factor related to the contact potential.
PMID- 28415184
TI - Multiscale structure of time series revealed by the monotony spectrum.
AB - Observation of complex systems produces time series with specific dynamics at
different time scales. The majority of the existing numerical methods for
multiscale analysis first decompose the time series into several simpler
components and the multiscale structure is given by the properties of their
components. We present a numerical method which describes the multiscale
structure of arbitrary time series without decomposing them. It is based on the
monotony spectrum defined as the variation of the mean amplitude of the monotonic
segments with respect to the mean local time scale during successive averagings
of the time series, the local time scales being the durations of the monotonic
segments. The maxima of the monotony spectrum indicate the time scales which
dominate the variations of the time series. We show that the monotony spectrum
can correctly analyze a diversity of artificial time series and can discriminate
the existence of deterministic variations at large time scales from the random
fluctuations. As an application we analyze the multifractal structure of some
hydrological time series.
PMID- 28415185
TI - Passive scalars: Mixing, diffusion, and intermittency in helical and nonhelical
rotating turbulence.
AB - We use direct numerical simulations to compute structure functions, scaling
exponents, probability density functions, and effective transport coefficients of
passive scalars in turbulent rotating helical and nonhelical flows. We show that
helicity affects the inertial range scaling of the velocity and of the passive
scalar when rotation is present, with a spectral law consistent with ~k_{?}^{
1.4} for the passive scalar variance spectrum. This scaling law is consistent
with a phenomenological argument [P. Rodriguez Imazio and P. D. Mininni, Phys.
Rev. E 83, 066309 (2011)PLEEE81539-375510.1103/PhysRevE.83.066309] for rotating
nonhelical flows, which follows directly from Kolmogorov-Obukhov scaling and
states that if energy follows a E(k)~k^{-n} law, then the passive scalar variance
follows a law V(k)~k^{-n_{theta}} with n_{theta}=(5-n)/2. With the second-order
scaling exponent obtained from this law, and using the Kraichnan model, we obtain
anomalous scaling exponents for the passive scalar that are in good agreement
with the numerical results. Multifractal intermittency models are also
considered. Intermittency of the passive scalar is stronger than in the
nonhelical rotating case, a result that is also confirmed by stronger non
Gaussian tails in the probability density functions of field increments. Finally,
Fick's law is used to compute the effective diffusion coefficients in the
directions parallel and perpendicular to rotation. Calculations indicate that
horizontal diffusion decreases in the presence of helicity in rotating flows,
while vertical diffusion increases. A simple mean field argument explains this
behavior in terms of the amplitude of velocity fluctuations.
PMID- 28415186
TI - Scaling of slip avalanches in sheared amorphous materials based on large-scale
atomistic simulations.
AB - Atomistic simulations of binary amorphous systems with over 4 million atoms are
performed. Systems of two interatomic potentials of the Lennard-Jones type, LJ12
6 and LJ9-6, are simulated. The athermal quasistatic shearing protocol is
adopted, where the shear strain is applied in a stepwise fashion with each step
followed by energy minimization. For each avalanche event, the shear stress drop
(Deltasigma), the hydrostatic pressure drop (Deltasigma_{h}), and the potential
energy drop (DeltaE) are computed. It is found that, with the avalanche size
increasing, the three become proportional to each other asymptotically. The
probability distributions of avalanche sizes are obtained and values of scaling
exponents fitted. In particular, the distributions follow a power law,
P(DeltaU)~DeltaU^{-tau}, where DeltaU is a measure of avalanche sizes defined
based on shear stress drops. The exponent tau is 1.25+/-0.1 for the LJ12-6
systems, and 1.15+/-0.1 for the LJ9-6 systems. The value of tau for the LJ12-6
systems is consistent with that from an earlier atomistic simulation study by
Robbins et al. [Phys. Rev. Lett. 109, 105703 (2012)]PRLTAO0031
900710.1103/PhysRevLett.109.105703, but the fitted values of other scaling
exponents differ, which may be because the shearing protocol used here differs
from that in their study.
PMID- 28415187
TI - Poverty index with time-varying consumption and income distributions.
AB - Starting from a stochastic agent-based model to represent market exchange in a
developing economy, we study time variations of the probability density function
of income with simultaneous variation of the consumption deprivation (CD), where
CD represents the shortfall in consumption from the saturation level of an
essential commodity, cereal. Together, these two models combine income
expenditure-based market dynamics with time variations in consumption due to
income. In this new unified theoretical structure, exchange of trade in assets is
only allowed when the income exceeds consumption-deprivation while CD itself is
endogenously obtained from a separate kinetic model. Our results reveal that the
nature of time variation of the CD function leads to a downward trend in the
threshold level of consumption of basic necessities, suggesting a possible
dietary transition in terms of lower saturation level of food-grain consumption,
possibly through an improvement in the level of living. The new poverty index,
defined as CD, is amenable to approximate probabilistic prediction within a short
time horizon. A major achievement of this work is the intrinsic independence of
the poverty index from an exogenous poverty line, making it more objective for
policy formulation as opposed to existing poverty indices in the literature.
PMID- 28415188
TI - Universality classes of fluctuation dynamics in hierarchical complex systems.
AB - A unified approach is proposed to describe the statistics of the short-time
dynamics of multiscale complex systems. The probability density function of the
relevant time series (signal) is represented as a statistical superposition of a
large time-scale distribution weighted by the distribution of certain internal
variables that characterize the slowly changing background. The dynamics of the
background is formulated as a hierarchical stochastic model whose form is derived
from simple physical constraints, which in turn restrict the dynamics to only two
possible classes. The probability distributions of both the signal and the
background have simple representations in terms of Meijer G functions. The two
universality classes for the background dynamics manifest themselves in the
signal distribution as two types of tails: power law and stretched exponential,
respectively. A detailed analysis of empirical data from classical turbulence and
financial markets shows excellent agreement with the theory.
PMID- 28415189
TI - Slip and barodiffusion phenomena in slow flows of a gas mixture.
AB - The slip and barodiffusion problems for the slow flows of a gas mixture are
investigated on the basis of the linearized moment equations following from the
Boltzmann equation. We restrict ourselves to the set of the third-order moment
equations and state two general relations (resembling conservation equations) for
the moments of the distribution function similar to the conditions used by
Loyalka [S. K. Loyalka, Phys. Fluids 14, 2291 (1971)10.1063/1.1693331] in his
approximation method (the modified Maxwell method). The expressions for the
macroscopic velocities of the gas mixture species, the partial viscous stress
tensors, and the reduced heat fluxes for the stationary slow flow of a gas
mixture in the semi-infinite space over a plane wall are obtained as a result of
the exact solution of the linearized moment equations in the 10- and 13-moment
approximations. The general expression for the slip velocity and the simple and
accurate expressions for the viscous, thermal, diffusion slip, and baroslip
coefficients, which are given in terms of the basic transport coefficients, are
derived by using the modified Maxwell method. The solutions of moment equations
are also used for investigation of the flow and diffusion of a gas mixture in a
channel formed by two infinite parallel plates. A fundamental result is that the
barodiffusion factor in the cross-section-averaged expression for the diffusion
flux contains contributions associated with the viscous transfer of momentum in
the gas mixture and the effect of the Knudsen layer. Our study revealed that the
barodiffusion factor is equal to the diffusion slip coefficient (correct to the
opposite sign). This result is consistent with the Onsager's reciprocity
relations for kinetic coefficients following from nonequilibrium thermodynamics
of the discontinuous systems.
PMID- 28415190
TI - Density-functional calculations of transport properties in the nondegenerate
limit and the role of electron-electron scattering.
AB - We compute electrical and thermal conductivities of hydrogen plasmas in the
nondegenerate regime using Kohn-Sham density functional theory (DFT) and an
application of the Kubo-Greenwood response formula, and demonstrate that for
thermal conductivity, the mean-field treatment of the electron-electron (e-e)
interaction therein is insufficient to reproduce the weak-coupling limit obtained
by plasma kinetic theories. An explicit e-e scattering correction to the DFT is
posited by appealing to Matthiessen's Rule and the results of our computations of
conductivities with the quantum Lenard-Balescu (QLB) equation. Further motivation
of our correction is provided by an argument arising from the Zubarev quantum
kinetic theory approach. Significant emphasis is placed on our efforts to produce
properly converged results for plasma transport using Kohn-Sham DFT, so that an
accurate assessment of the importance and efficacy of our e-e scattering
corrections to the thermal conductivity can be made.
PMID- 28415191
TI - Random walk in nonhomogeneous environments: A possible approach to human and
animal mobility.
AB - The random walk process in a nonhomogeneous medium, characterized by a Levy
stable distribution of jump length, is discussed. The width depends on a
position: either before the jump or after that. In the latter case, the density
slope is affected by the variable width and the variance may be finite; then all
kinds of the anomalous diffusion are predicted. In the former case, only the time
characteristics are sensitive to the variable width. The corresponding Langevin
equation with different interpretations of the multiplicative noise is discussed.
The dependence of the distribution width on position after jump is interpreted in
terms of cognitive abilities and related to such problems as migration in a human
population and foraging habits of animals.
PMID- 28415192
TI - Multiple-node basin stability in complex dynamical networks.
AB - Dynamical entities interacting with each other on complex networks often exhibit
multistability. The stability of a desired steady regime (e.g., a synchronized
state) to large perturbations is critical in the operation of many real-world
networked dynamical systems such as ecosystems, power grids, the human brain,
etc. This necessitates the development of appropriate quantifiers of stability of
multiple stable states of such systems. Motivated by the concept of basin
stability (BS) [P. J. Menck et al., Nat. Phys. 9, 89 (2013)1745
247310.1038/nphys2516], we propose here the general framework of multiple-node
basin stability for gauging the global stability and robustness of networked
dynamical systems in response to nonlocal perturbations simultaneously affecting
multiple nodes of a system. The framework of multiple-node BS provides an
estimate of the critical number of nodes that, when simultaneously perturbed,
significantly reduce the capacity of the system to return to the desired stable
state. Further, this methodology can be applied to estimate the minimum number of
nodes of the network to be controlled or safeguarded from external perturbations
to ensure proper operation of the system. Multiple-node BS can also be utilized
for probing the influence of spatially localized perturbations or targeted
attacks to specific parts of a network. We demonstrate the potential of multiple
node BS in assessing the stability of the synchronized state in a deterministic
scale-free network of Rossler oscillators and a conceptual model of the power
grid of the United Kingdom with second-order Kuramoto-type nodal dynamics.
PMID- 28415193
TI - Minimum memory for generating rare events.
AB - We classify the rare events of structured, memoryful stochastic processes and use
this to analyze sequential and parallel generators for these events. Given a
stochastic process, we introduce a method to construct a process whose typical
realizations are a given process' rare events. This leads to an expression for
the minimum memory required to generate rare events. We then show that the
recently discovered classical-quantum ambiguity of simplicity also occurs when
comparing the structure of process fluctuations.
PMID- 28415194
TI - Migration of a droplet in a cylindrical tube in the creeping flow regime.
AB - The migration of a neutrally buoyant droplet in a tube containing another
immiscible liquid is investigated numerically in the creeping flow regime. A
fully developed velocity profile is imposed at the inlet of the tube. The
interface between the two immiscible fluids is captured using a coupled level-set
and volume-of-fluid approach. The deformation and breakup dynamics of the droplet
are investigated in terms of three dimensionless parameters, namely, the ratio
between the radius of the undeformed droplet and the radius of the capillary
tube, the viscosity ratio between the dispersed and the continuous phases, and
the capillary number that measures the relative importance of the viscous force
over the surface tension force. It has been observed that the droplet, while
traversing through the tube, either approaches a steady bulletlike shape or
develops a prominent reentrant cavity at its rear. Depending on the initial
droplet size, there exists a critical capillary number for every flow
configuration beyond which the drop fails to maintain a steady shape and breaks
into fragments. The deformation and breakup phenomena depend primarily on the
droplet size, the viscosity ratio, and the capillary number. Special attention
has been given to the case where the drop diameter is comparable with the tube
diameter. A thorough computational study has been conducted to find the critical
capillary number for a range of droplets of varied sizes suspended in systems
having different viscosity ratios.
PMID- 28415195
TI - Ultrafast probing of magnetic field growth inside a laser-driven solenoid.
AB - We report on the detection of the time-dependent B-field amplitude and topology
in a laser-driven solenoid. The B-field inferred from both proton deflectometry
and Faraday rotation ramps up linearly in time reaching 210 +/- 35 T at the end
of a 0.75-ns laser drive with 1 TW at 351 nm. A lumped-element circuit model
agrees well with the linear rise and suggests that the blow-off plasma screens
the field between the plates leading to an increased plate capacitance that
converts the laser-generated hot-electron current into a voltage source that
drives current through the solenoid. ALE3D modeling shows that target disassembly
and current diffusion may limit the B-field increase for longer laser drive.
Scaling of these experimental results to a National Ignition Facility (NIF)
hohlraum target size (~0.2cm^{3}) indicates that it is possible to achieve
several tens of Tesla.
PMID- 28415196
TI - Traffic gridlock on a honeycomb city.
AB - Inspired by an old and almost in oblivion urban plan, we report the behavior of
the Biham-Middleton-Levine (BML) model-a paradigm for studying phase transitions
of traffic flow-on a hypothetical city with a perfect honeycomb street network.
In contrast with the original BML model on a square lattice, the same model on a
honeycomb does not show any anisotropy or intermediate states, but a single
continuous phase transition between free and totally congested flow, a transition
that can be completely characterized by the tools of classical percolation.
Although the transition occurs at a lower density than for the conventional BML,
simple modifications, like randomly stopping the cars with a very small
probability or increasing the traffic light periods, drives the model to perform
better on honeycomb lattices. As traffic lights and disordered perturbations are
inherent in real traffic, these results question the actual role of the square
gridlike designs and suggest the honeycomb topology as an interesting alternative
for urban planning in real cities.
PMID- 28415197
TI - Quantum walks: The first detected passage time problem.
AB - Even after decades of research, the problem of first passage time statistics for
quantum dynamics remains a challenging topic of fundamental and practical
importance. Using a projective measurement approach, with a sampling time tau, we
obtain the statistics of first detection events for quantum dynamics on a
lattice, with the detector located at the origin. A quantum renewal equation for
a first detection wave function, in terms of which the first detection
probability can be calculated, is derived. This formula gives the relation
between first detection statistics and the solution of the corresponding
Schrodinger equation in the absence of measurement. We illustrate our results
with tight-binding quantum walk models. We examine a closed system, i.e., a ring,
and reveal the intricate influence of the sampling time tau on the statistics of
detection, discussing the quantum Zeno effect, half dark states, revivals, and
optimal detection. The initial condition modifies the statistics of a quantum
walk on a finite ring in surprising ways. In some cases, the average detection
time is independent of the sampling time while in others the average exhibits
multiple divergences as the sampling time is modified. For an unbounded one
dimensional quantum walk, the probability of first detection decays like
(time)^{(-3)} with superimposed oscillations, with exceptional behavior when the
sampling period tau times the tunneling rate gamma is a multiple of pi/2. The
amplitude of the power-law decay is suppressed as tau->0 due to the Zeno effect.
Our work, an extended version of our previously published paper, predicts rich
physical behaviors compared with classical Brownian motion, for which the first
passage probability density decays monotonically like (time)^{-3/2}, as
elucidated by Schrodinger in 1915.
PMID- 28415198
TI - Recommender engine for continuous-time quantum Monte Carlo methods.
AB - Recommender systems play an essential role in the modern business world. They
recommend favorable items such as books, movies, and search queries to users
based on their past preferences. Applying similar ideas and techniques to Monte
Carlo simulations of physical systems boosts their efficiency without sacrificing
accuracy. Exploiting the quantum to classical mapping inherent in the continuous
time quantum Monte Carlo methods, we construct a classical molecular gas model to
reproduce the quantum distributions. We then utilize powerful molecular
simulation techniques to propose efficient quantum Monte Carlo updates. The
recommender engine approach provides a general way to speed up the quantum
impurity solvers.
PMID- 28415199
TI - Identifying polymer states by machine learning.
AB - The ability of a feed-forward neural network to learn and classify different
states of polymer configurations is systematically explored. Performing numerical
experiments, we find that a simple network model can, after adequate training,
recognize multiple structures, including gaslike coil, liquidlike globular, and
crystalline anti-Mackay and Mackay structures. The network can be trained to
identify the transition points between various states, which compare well with
those identified by independent specific-heat calculations. Our study
demonstrates that neural networks provide an unconventional tool to study the
phase transitions in polymeric systems.
PMID- 28415200
TI - Triangles bridge the scales: Quantifying cellular contributions to tissue
deformation.
AB - In this article, we propose a general framework to study the dynamics and
topology of cellular networks that capture the geometry of cell packings in two
dimensional tissues. Such epithelia undergo large-scale deformation during
morphogenesis of a multicellular organism. Large-scale deformations emerge from
many individual cellular events such as cell shape changes, cell rearrangements,
cell divisions, and cell extrusions. Using a triangle-based representation of
cellular network geometry, we obtain an exact decomposition of large-scale
material deformation. Interestingly, our approach reveals contributions of
correlations between cellular rotations and elongation as well as cellular growth
and elongation to tissue deformation. Using this triangle method, we discuss
tissue remodeling in the developing pupal wing of the fly Drosophila
melanogaster.
PMID- 28415201
TI - Self-adjustment and disintegration threshold of Langmuir solitons in
inhomogeneous plasmas.
AB - Dynamics of Langmuir solitons in the presence of a background density gradient is
investigated numerically, including cases with steep gradients to the extent the
solitons can disintegrate. The disintegration threshold is explained by regarding
the electric field part of the soliton as a point mass moving along the self
generated potential well corresponding to the density cavity. On the other hand,
it is demonstrated that the Langmuir solitons are robust when the density
gradient is below the threshold. During the acceleration phase toward low density
regions, Langmuir solitons adjust themselves to balance the electric field
pressure and the negative plasma pressure by expelling the imbalanced portion as
density cavities at the sound velocity. When the density gradient is below the
disintegration threshold, the electric field part of the soliton bounces back and
forth within the potential well suggesting the solitons have internal structures.
PMID- 28415202
TI - Efficient approach to the free energy of crystals via Monte Carlo simulations:
Application to continuous and orientation-dependent potentials.
AB - We extend a recently proposed approach to determine the absolute free energy of
crystalline phases [Phys. Rev. E 92, 022103 (2015)PLEEE81539
375510.1103/PhysRevE.92.022103] to systems with continuous and orientation
dependent potentials. The method is based on the Monte Carlo thermodynamic
integration method, and it provides a general procedure to obtain a simple,
analytical, and exact reference free energy, together with an easy and accurate
thermodynamic coupling integral. The approach is free from the difficulties of
the standard method based on the harmonic coupling potential. A comparative
discussion of both approaches is provided.
PMID- 28415203
TI - Transfer entropy in continuous time, with applications to jump and neural spiking
processes.
AB - Transfer entropy has been used to quantify the directed flow of information
between source and target variables in many complex systems. While transfer
entropy was originally formulated in discrete time, in this paper we provide a
framework for considering transfer entropy in continuous time systems, based on
Radon-Nikodym derivatives between measures of complete path realizations. To
describe the information dynamics of individual path realizations, we introduce
the pathwise transfer entropy, the expectation of which is the transfer entropy
accumulated over a finite time interval. We demonstrate that this formalism
permits an instantaneous transfer entropy rate. These properties are analogous to
the behavior of physical quantities defined along paths such as work and heat. We
use this approach to produce an explicit form for the transfer entropy for pure
jump processes, and highlight the simplified form in the specific case of point
processes (frequently used in neuroscience to model neural spike trains).
Finally, we present two synthetic spiking neuron model examples to exhibit the
pertinent features of our formalism, namely, that the information flow for point
processes consists of discontinuous jump contributions (at spikes in the target)
interrupting a continuously varying contribution (relating to waiting times
between target spikes). Numerical schemes based on our formalism promise
significant benefits over existing strategies based on discrete time formalisms.
PMID- 28415204
TI - Dramatic effect of fluid chemistry on cornstarch suspensions: Linking particle
interactions to macroscopic rheology.
AB - Suspensions of cornstarch in water exhibit strong dynamic shear thickening. We
show that partly replacing water with ethanol strongly alters the suspension
rheology. We perform steady and nonsteady rheology measurements combined with
atomic force microscopy to investigate the role of fluid chemistry on the
macroscopic rheology of the suspensions and its link with the interactions
between cornstarch grains. Upon increasing the ethanol content, the suspension
goes through a yield-stress fluid state and ultimately becomes a shear-thinning
fluid. On the cornstarch grain scale, atomic force microscopy measurements reveal
the presence of polymers on the cornstarch surface, which exhibit a cosolvency
effect. At intermediate ethanol content, a maximum of polymer solubility induces
high microscopic adhesion which we relate to the macroscopic yield stress.
PMID- 28415205
TI - Cross-symmetric dipolar-matter-wave solitons in double-well chains.
AB - We consider a dipolar Bose-Einstein condensate trapped in an array of two-well
systems with an arbitrary orientation of the dipoles relative to the system's
axis. The system can be built as a chain of local traps sliced into two parallel
lattices by a repelling laser sheet. It is modeled by a pair of coupled discrete
Gross-Pitaevskii equations, with dipole-dipole self-interactions and cross
interactions. When the dipoles are not polarized perpendicular or parallel to the
lattice, the cross interaction is asymmetric, replacing the familiar symmetric
two-component discrete solitons by two new species of cross-symmetric ones, viz.,
on-site- and off-site-centered solitons, which are strongly affected by the
orientation of the dipoles and separation between the parallel lattices. A very
narrow region of intermediate asymmetric discrete solitons is found at the
boundary between the on- and off-site families. Two different types of solitons
in the PT-symmetric version of the system are constructed too, and stability
areas are identified for them.
PMID- 28415206
TI - Chimera patterns in two-dimensional networks of coupled neurons.
AB - We discuss synchronization patterns in networks of FitzHugh-Nagumo and leaky
integrate-and-fire oscillators coupled in a two-dimensional toroidal geometry. A
common feature between the two models is the presence of fast and slow dynamics,
a typical characteristic of neurons. Earlier studies have demonstrated that both
models when coupled nonlocally in one-dimensional ring networks produce chimera
states for a large range of parameter values. In this study, we give evidence of
a plethora of two-dimensional chimera patterns of various shapes, including
spots, rings, stripes, and grids, observed in both models, as well as additional
patterns found mainly in the FitzHugh-Nagumo system. Both systems exhibit
multistability: For the same parameter values, different initial conditions give
rise to different dynamical states. Transitions occur between various patterns
when the parameters (coupling range, coupling strength, refractory period, and
coupling phase) are varied. Many patterns observed in the two models follow
similar rules. For example, the diameter of the rings grows linearly with the
coupling radius.
PMID- 28415208
TI - X-ray shadow imprint of hydrodynamic instabilities on the surface of inertial
confinement fusion capsules by the fuel fill tube.
AB - Measurements of hydrodynamic instability growth for a high-density carbon ablator
for indirectly driven inertial confinement fusion implosions on the National
Ignition Facility are reported. We observe significant unexpected features on the
capsule surface created by shadows of the capsule fill tube, as illuminated by
laser-irradiated x-ray spots on the hohlraum wall. These shadows increase the
spatial size and shape of the fill tube perturbation in a way that can
significantly degrade performance in layered implosions compared to previous
expectations. The measurements were performed at a convergence ratio of ~2 using
in-flight x-ray radiography. The initial seed due to shadow imprint is estimated
to be equivalent to ~50-100 nm of solid ablator material. This discovery has
prompted the need for a mitigation strategy for future inertial confinement
fusion designs as proposed here.
PMID- 28415207
TI - Model of polar auxin transport coupled to mechanical forces retrieves robust
morphogenesis along the Arabidopsis root.
AB - Stem cells are identical in many scales, they share the same molecular
composition, DNA, genes, and genetic networks, yet they should acquire different
properties to form a functional tissue. Therefore, they must interact and get
some external information from their environment, either spatial (dynamical
fields) or temporal (lineage). In this paper we test to what extent coupled
chemical and physical fields can underlie the cell's positional information
during development. We choose the root apical meristem of Arabidopsis thaliana to
model the emergence of cellular patterns. We built a model to study the dynamics
and interactions between the cell divisions, the local auxin concentration, and
physical elastic fields. Our model recovers important aspects of the self
organized and resilient behavior of the observed cellular patterns in the
Arabidopsis root, in particular, the reverse fountain pattern observed in the
auxin transport, the PIN-FORMED (protein family of auxin transporters)
polarization pattern and the accumulation of auxin near the region of maximum
curvature in a bent root. Our model may be extended to predict altered cellular
patterns that are expected under various applied auxin treatments or modified
physical growth conditions.
PMID- 28415209
TI - Onset of anomalous diffusion in colloids confined to quasimonolayers.
AB - It has been recently shown that a colloidal monolayer, e.g., formed at a fluid
interface or by means of a suitable confining potential, exhibits anomalous
collective diffusion. This is a consequence of the hydrodynamic interactions
mediated by the three-dimensional (3D) ambient fluid when the particles are
confined to reside on a two-dimensional (2D) manifold. We study theoretically and
with numerical simulations the crossover from normal to anomalous diffusion as
the particles are, in real systems, confined by a 3D external potential and thus
have the possibility to fluctuate out of the 2D manifold, thus forming a
quasimonolayer.
PMID- 28415210
TI - Ultraslow diffusion and weak ergodicity breaking in right triangular billiards.
AB - We investigate the diffusion behavior of a right triangular billiard system by
transforming its dynamics to a two-dimensional piecewise map. We find that the
diffusion in the momentum space is ultraslow, i.e., the mean squared displacement
grows asymptotically as the square of the logarithm of time. The mechanism of the
ultraslow diffusion behavior is explained and numerical evidence corroborating
our conclusion is provided. The weak ergodicity breaking of the system is also
discussed.
PMID- 28415211
TI - Dynamics of vortex-antivortex pairs and rarefaction pulses in liquid light.
AB - We present a numerical study of the cubic-quintic nonlinear Schrodinger equation
in two transverse dimensions, relevant for the propagation of light in certain
exotic media. A well-known feature of the model is the existence of flat-top
bright solitons of fixed intensity, whose dynamics resembles the physics of a
liquid. They support traveling wave solutions, consisting of rarefaction pulses
and vortex-antivortex pairs. In this work, we demonstrate how the vortex
antivortex pairs can be generated in bright soliton collisions displaying
destructive interference followed by a snake instability. We then discuss the
collisional dynamics of the dark excitations for different initial conditions. We
describe a number of distinct phenomena including vortex exchange modes,
quasielastic flyby scattering, solitonlike crossing, fully inelastic collisions,
and rarefaction pulse merging.
PMID- 28415213
TI - Non-Gaussian limit fluctuations in active swimmer suspensions.
AB - We investigate the hydrodynamic fluctuations in suspensions of swimming
microorganisms (Chlamydomonas) by observing the probe particles dispersed in the
media. Short-term fluctuations of probe particles were superdiffusive and
displayed heavily tailed non-Gaussian distributions. The analytical theory that
explains the observed distribution was derived by summing the power-law-decaying
hydrodynamic interactions from spatially distributed field sources (here,
swimming microorganisms). The summing procedure, which we refer to as the
physical limit operation, is applicable to a variety of physical fluctuations to
which the classical central limiting theory does not apply. Extending the
analytical formula to compare to experiments in active swimmer suspensions, we
show that the non-Gaussian shape of the observed distribution obeys the analytic
theory concomitantly with independently determined parameters such as the
strength of force generations and the concentration of Chlamydomonas. Time
evolution of the distributions collapsed to a single master curve, except for
their extreme tails, for which our theory presents a qualitative explanation.
Investigations thereof and the complete agreement with theoretical predictions
revealed broad applicability of the formula to dispersions of active sources of
fluctuations.
PMID- 28415212
TI - Scaling laws of reflection coefficients of quantum waves at a Cantor-like
potential.
AB - We reconsider a one-dimensional scattering problem in the Schrodinger equation
with a Cantor-like potential. The reflection coefficient obeys a scaling law for
sufficiently large wave number k. The scaling law is expressed with a universal
function characterized by a multifractal.
PMID- 28415214
TI - Stochastic thermodynamics for Ising chain and symmetric exclusion process.
AB - We verify the finite-time fluctuation theorem for a linear Ising chain in contact
with heat reservoirs at its ends. Analytic results are derived for a chain
consisting of two spins. The system can be mapped onto a model for particle
transport, namely, the symmetric exclusion process in contact with thermal and
particle reservoirs. We modify the symmetric exclusion process to represent a
thermal engine and reproduce universal features of the efficiency at maximum
power.
PMID- 28415215
TI - Levy flight with absorption: A model for diffusing diffusivity with long tails.
AB - We consider diffusion of a particle in rearranging environment, so that the
diffusivity of the particle is a stochastic function of time. In our previous
model of "diffusing diffusivity" [Jain and Sebastian, J. Phys. Chem. B 120, 3988
(2016)JPCBFK1520-610610.1021/acs.jpcb.6b01527], it was shown that the mean square
displacement of particle remains Fickian, i.e., ?T at all times, but
the probability distribution of particle displacement is not Gaussian at all
times. It is exponential at short times and crosses over to become Gaussian only
in a large time limit in the case where the distribution of D in that model has a
steady state limit which is exponential, i.e., pi_{e}(D)~e^{-D/D_{0}}. In the
present study, we model the diffusivity of a particle as a Levy flight process so
that D has a power-law tailed distribution, viz., pi_{e}(D)~D^{-1-alpha} with
0 is slow. Such process is characterized by the power-law growth of
the largest possible observable value of N at a given time t. We find similar
features also for the reverse process of the regression from a rare state with
N? to a typical one with N?.
PMID- 28415227
TI - Fluctuation loops in noise-driven linear dynamical systems.
AB - Understanding the spatiotemporal structure of most probable fluctuation pathways
to rarely occurring states is a central problem in the study of noise-driven,
nonequilibrium dynamical systems. When the underlying system does not possess
detailed balance, the optimal fluctuation pathway to a particular state and
relaxation pathway from that state may combine to form a looplike structure in
the system phase space called a fluctuation loop. Here, fluctuation loops are
studied in a linear circuit model consisting of coupled RC elements, where each
element is driven by its own independent noise source. Using a stochastic
Hamiltonian approach, we determine the optimal fluctuation pathways, and
analytically construct corresponding fluctuation loops. To quantitatively
characterize fluctuation loops, we study the time-dependent area tensor that is
swept out by individual stochastic trajectories in the system phase space. At
long times, the area tensor scales linearly with time, with a coefficient that
precisely vanishes when the system satisfies detailed balance.
PMID- 28415229
TI - Phase behavior and characterization of heptamethyltrisiloxane-based de Vries
smectic liquid crystal by electro-optics, x rays, and dielectric spectroscopy.
AB - A heptamethyltrisiloxane liquid crystal (LC) exhibiting I-SmA^{*}-SmC^{*} phases
has been characterized by calorimetry, polarizing microscopy, x-ray diffraction,
electro-optics, and dielectric spectroscopy. Observations of a large
electroclinic effect, a large increase in the birefringence (Deltan) with
electric field, a low shrinkage in the layer thickness (~1.75%) at 20 degrees C
below the SmA^{*}-SmC^{*} transition, and low values of the reduction factor
(~0.40) suggest that the SmA^{*} phase in this material is of the de Vries type.
The reduction factor is a measure of the layer shrinkage in the SmC^{*} phase and
it should be zero for an ideal de Vries. Moreover, a decrease in the magnitude of
Deltan with decreasing temperature indicates the presence of the temperature
dependent tilt angle in the SmA^{*} phase. The electro-optic behavior is
explained by the generalized Langevin-Debye model as given by Shen et al. [Y.
Shen et al., Phys. Rev. E 88, 062504 (2013)10.1103/PhysRevE.88.062504]. The soft
mode dielectric relaxation strength shows a critical behavior when the system
goes from the SmA^{*} to the SmC^{*} phase.
PMID- 28415230
TI - Scale-invariant puddles in graphene: Geometric properties of electron-hole
distribution at the Dirac point.
AB - We characterize the carrier density profile of the ground state of graphene in
the presence of particle-particle interaction and random charged impurity in zero
gate voltage. We provide detailed analysis on the resulting spatially
inhomogeneous electron gas, taking into account the particle-particle interaction
and the remote Coulomb disorder on an equal footing within the Thomas-Fermi-Dirac
theory. We present some general features of the carrier density probability
measure of the graphene sheet. We also show that, when viewed as a random
surface, the electron-hole puddles at zero chemical potential show peculiar self
similar statistical properties. Although the disorder potential is chosen to be
Gaussian, we show that the charge field is non-Gaussian with unusual Kondev
relations, which can be regarded as a new class of two-dimensional random-field
surfaces. Using Schramm-Loewner (SLE) evolution, we numerically demonstrate that
the ungated graphene has conformal invariance and the random zero-charge density
contours are SLE_{kappa} with kappa=1.8+/-0.2, consistent with c=-3 conformal
field theory.
PMID- 28415231
TI - Gap solitons in Rabi lattices.
AB - We introduce a two-component one-dimensional system, which is based on two
nonlinear Schrodinger or Gross-Pitaevskii equations (GPEs) with spatially
periodic modulation of linear coupling ("Rabi lattice") and self-repulsive
nonlinearity. The system may be realized in a binary Bose-Einstein condensate,
whose components are resonantly coupled by a standing optical wave, as well as in
terms of the bimodal light propagation in periodically twisted waveguides. The
system supports various types of gap solitons (GSs), which are constructed, and
their stability is investigated, in the first two finite bandgaps of the
underlying spectrum. These include on- and off-site-centered solitons (the GSs of
the off-site type are additionally categorized as spatially even and odd ones),
which may be symmetric or antisymmetric, with respect to the coupled components.
The GSs are chiefly stable in the first finite bandgap and unstable in the second
one. In addition to that, there are narrow regions near the right edge of the
first bandgap, and in the second one, which feature intricate alternation of
stability and instability. Unstable solitons evolve into robust breathers or
spatially confined turbulent modes. On-site-centered GSs are also considered in a
version of the system that is made asymmetric by the Zeeman effect, or by
birefringence of the optical waveguide. A region of alternate stability is found
in the latter case too. In the limit of strong asymmetry, GSs are obtained in a
semianalytical approximation, which reduces two coupled GPEs to a single one with
an effective lattice potential.
PMID- 28415232
TI - Certain bright soliton interactions of the Sasa-Satsuma equation in a monomode
optical fiber.
AB - Under investigation in this paper is the Sasa-Satsuma equation, which describes
the propagation of ultrashort pulses in a monomode fiber with the third-order
dispersion, self-steepening, and stimulated Raman scattering effects. Based on
the known bilinear forms, through the modified expanded formulas and symbolic
computation, we construct the bright two-soliton solutions. Through classifying
the interactions under different parameter conditions, we reveal six cases of
interactions between the two solitons via an asymptotic analysis. With the help
of the analytic and graphic analysis, we find that such interactions are
different from those of the nonlinear Schrodinger equation and Hirota equation.
When those solitons interact with each other, the singular-I soliton is shape
preserving, while the singular-II and nonsingular solitons may be shape
preserving or shape changing. Such elastic and inelastic interaction phenomena in
a scalar equation might enrich the knowledge of soliton behavior, which could be
expected to be experimentally observed.
PMID- 28415233
TI - Two mechanisms forming a comblike step pattern induced by a moving linear adatom
source.
AB - We carry out phase field simulations to study properties of the comblike step
patterns induced by an adatom source. When an adatom source advances right in
front of a step, step wandering is caused by the asymmetry of the surface
diffusion field and small protrusions are formed. If the velocity of the source
V_{p} is smaller than a critical value V_{p}^{c}, the protrusions follow the
adatom source with coarsening of the step pattern, and a regular comblike pattern
with finger-like protrusions is formed. With a sufficiently small V_{p}, the gap
of the supersaturation is large at the adatom source. Since the period of
protrusions, Lambda, decreases with increasing V_{p}, the coarsening of step
pattern is irrelevant for the protrusions to catch up with the adatom source.
Near V_{p}^{c}, the gap of the supersaturation at the adatom source is small.
Taking account of the increase in Lambda with increasing V_{p}, the coarsening of
the step pattern is essential for the protrusions to follow the adatom source.
PMID- 28415234
TI - Global relativistic effects in chaotic scattering.
AB - The phenomenon of chaotic scattering is very relevant in different fields of
science and engineering. It has been mainly studied in the context of Newtonian
mechanics, where the velocities of the particles are low in comparison with the
speed of light. Here, we analyze global properties such as the escape time
distribution and the decay law of the Henon-Heiles system in the context of
special relativity. Our results show that the average escape time decreases with
increasing values of the relativistic factor beta. As a matter of fact, we have
found a crossover point for which the KAM islands in the phase space are
destroyed when beta?0.4. On the other hand, the study of the survival probability
of particles in the scattering region shows an algebraic decay for values of
beta<=0.4, and this law becomes exponential for beta>0.4. Surprisingly, a scaling
law between the exponent of the decay law and the beta factor is uncovered where
a quadratic fitting between them is found. The results of our numerical
simulations agree faithfully with our qualitative arguments. We expect this work
to be useful for a better understanding of both chaotic and relativistic systems.
PMID- 28415235
TI - General velocity, pressure, and initial condition for two-dimensional and three
dimensional lattice Boltzmann simulations.
AB - In this paper, an alternative approach to implement initial and boundary
conditions in the lattice Boltzmann method is presented. The main idea is to
approximate the nonequilibrium component of distribution functions as a third
order power series in the lattice velocities and formulate a procedure to
determine boundary node distributions by using fluid variables, consistent with
such an expansion. The velocity shift associated with the body force effects is
included in this scheme, along with an approximation to determine the mass
density in complex geometries. Different strategies based on the present scheme
are developed to implement velocity and pressure conditions for arbitrarily
shaped boundaries, using the D2Q9, D3Q15, D3Q19 and D3Q27 lattices, in two and
three space dimensions, respectively. The proposed treatment is tested against
several well-established problems, showing second-order spatial accuracy and
often improved behavior as compared to various existing methods, with no
appreciable computational overhead.
PMID- 28415236
TI - Globally attracting synchrony in a network of oscillators with all-to-all
inhibitory pulse coupling.
AB - The synchronization tendencies of networks of oscillators have been studied
intensely. We assume a network of all-to-all pulse-coupled oscillators in which
the effect of a pulse is independent of the number of oscillators that
simultaneously emit a pulse and the normalized delay (the phase resetting) is a
monotonically increasing function of oscillator phase with the slope everywhere
less than 1 and a value greater than 2phi-1, where phi is the normalized phase.
Order switching cannot occur; the only possible solutions are globally attracting
synchrony and cluster solutions with a fixed firing order. For small conduction
delays, we prove the former stable and all other possible attractors nonexistent
due to the destabilizing discontinuity of the phase resetting at a phase of 0.
PMID- 28415237
TI - Latent geometry of bipartite networks.
AB - Despite the abundance of bipartite networked systems, their organizing principles
are less studied compared to unipartite networks. Bipartite networks are often
analyzed after projecting them onto one of the two sets of nodes. As a result of
the projection, nodes of the same set are linked together if they have at least
one neighbor in common in the bipartite network. Even though these projections
allow one to study bipartite networks using tools developed for unipartite
networks, one-mode projections lead to significant loss of information and
artificial inflation of the projected network with fully connected subgraphs.
Here we pursue a different approach for analyzing bipartite systems that is based
on the observation that such systems have a latent metric structure: network
nodes are points in a latent metric space, while connections are more likely to
form between nodes separated by shorter distances. This approach has been
developed for unipartite networks, and relatively little is known about its
applicability to bipartite systems. Here, we fully analyze a simple latent
geometric model of bipartite networks and show that this model explains the
peculiar structural properties of many real bipartite systems, including the
distributions of common neighbors and bipartite clustering. We also analyze the
geometric information loss in one-mode projections in this model and propose an
efficient method to infer the latent pairwise distances between nodes. Uncovering
the latent geometry underlying real bipartite networks can find applications in
diverse domains, ranging from constructing efficient recommender systems to
understanding cell metabolism.
PMID- 28415238
TI - Optimizing interconnections to maximize the spectral radius of interdependent
networks.
AB - The spectral radius (i.e., the largest eigenvalue) of the adjacency matrices of
complex networks is an important quantity that governs the behavior of many
dynamic processes on the networks, such as synchronization and epidemics. Studies
in the literature focused on bounding this quantity. In this paper, we
investigate how to maximize the spectral radius of interdependent networks by
optimally linking k internetwork connections (or interconnections for short). We
derive formulas for the estimation of the spectral radius of interdependent
networks and employ these results to develop a suite of algorithms that are
applicable to different parameter regimes. In particular, a simple algorithm is
to link the k nodes with the largest k eigenvector centralities in one network to
the node in the other network with a certain property related to both networks.
We demonstrate the applicability of our algorithms via extensive simulations. We
discuss the physical implications of the results, including how the optimal
interconnections can more effectively decrease the threshold of epidemic
spreading in the susceptible-infected-susceptible model and the threshold of
synchronization of coupled Kuramoto oscillators.
PMID- 28415239
TI - Motility of Escherichia coli in a quasi-two-dimensional porous medium.
AB - Bacterial migration through confined spaces is critical for several phenomena,
such as biofilm formation, bacterial transport in soils, and bacterial therapy
against cancer. In the present work, E. coli (strain K12-MG1655 WT) motility was
characterized by recording and analyzing individual bacterium trajectories in a
simulated quasi-two-dimensional porous medium. The porous medium was simulated by
enclosing, between slide and cover slip, a bacterial-culture sample mixed with
uniform 2.98-MUm-diameter spherical latex particles. The porosity of the medium
was controlled by changing the latex particle concentration. By statistically
analyzing several trajectory parameters (instantaneous velocity, turn angle, mean
squared displacement, etc.), and contrasting with the results of a random-walk
model developed ad hoc, we were able to quantify the effects that different
obstacle concentrations have upon bacterial motility.
PMID- 28415240
TI - Density-functional theory for fluid-solid and solid-solid phase transitions.
AB - We develop a theory to describe solid-solid phase transitions. The density
functional formalism of classical statistical mechanics is used to find an exact
expression for the difference in the grand thermodynamic potentials of the two
coexisting phases. The expression involves both the symmetry conserving and the
symmetry broken parts of the direct pair correlation function. The theory is used
to calculate phase diagram of systems of soft spheres interacting via inverse
power potentials u(r)=epsilon(sigma/r)^{n}, where parameter n measures softness
of the potential. We find that for 1/n<0.154 systems freeze into the face
centered cubic (fcc) structure while for 1/n>=0.154 the body-centred-cubic (bcc)
structure is preferred. The bcc structure transforms into the fcc structure upon
increasing the density. The calculated phase diagram is in good agreement with
the one found from molecular simulations.
PMID- 28415241
TI - Emergence of chimeras through induced multistability.
AB - Chimeras, namely coexisting desynchronous and synchronized dynamics, are formed
in an ensemble of identically coupled identical chaotic oscillators when the
coupling induces multiple stable attractors, and further when the basins of the
different attractors are intertwined in a complex manner. When there is coupling
induced multistability, an ensemble of identical chaotic oscillators-with global
coupling, or also under the influence of common noise or an external drive
(chaotic, periodic, or quasiperiodic)-inevitably exhibits chimeric behavior.
Induced multistability in the system leads to the formation of distinct
subpopulations, one or more of which support synchronized dynamics, while in
others the motion is asynchronous or incoherent. We study the mechanism for the
emergence of such chimeric states, and we discuss the generality of our results.
PMID- 28415242
TI - Renormalization-group theory for cooling first-order phase transitions in Potts
models.
AB - We develop a dynamic field-theoretic renormalization-group (RG) theory for
cooling first-order phase transitions in the Potts model. It is suggested that
the well-known imaginary fixed points of the q-state Potts model for q>10/3 in
the RG theory are the origin of the dynamic scaling found recently from numerical
simulations, apart from logarithmic corrections. This indicates that the real and
imaginary fixed points of the Potts model are both physical and control the
scalings of the continuous and discontinuous phase transitions, respectively, of
the model. Our one-loop results for the scaling exponents are already not far
away from the numerical results. Further, the scaling exponents depend on q only
slightly, consistent with the numerical results. Therefore, the theory is
believed to provide a natural explanation of the dynamic scaling including the
scaling exponents and their scaling laws for various observables in the cooling
first-order phase transition of the Potts model.
PMID- 28415243
TI - Numerical linked cluster expansions for quantum quenches in one-dimensional
lattices.
AB - We discuss the application of numerical linked cluster expansions (NLCEs) to
study one dimensional lattice systems in thermal equilibrium and after quantum
quenches from thermal equilibrium states. For the former, we calculate
observables in the grand canonical ensemble, and for the latter we calculate
observables in the diagonal ensemble. When converged, NLCEs provide results in
the thermodynamic limit. We use two different NLCEs: a maximally connected
expansion introduced in previous works and a site-based expansion. We compare the
effectiveness of both NLCEs. The site-based NLCE is found to work best for
systems in thermal equilibrium. However, in thermal equilibrium and after quantum
quenches, the site-based NLCE can diverge when the maximally connected one
converges. We relate this divergence to the exponentially large number of
clusters in the site-based NLCE and the behavior of the weights of observables in
those clusters. We discuss the effectiveness of resummations to cure the
divergence. Our NLCE calculations are compared to exact diagonalization ones in
lattices with periodic boundary conditions. NLCEs are found to outperform exact
diagonalization in periodic systems for all quantities studied.
PMID- 28415244
TI - Effect of the salt-induced micellar microstructure on the nonlinear shear flow
behavior of ionic cetylpyridinium chloride surfactant solutions.
AB - The shear flow dynamics of linear and branched wormlike micellar systems based on
cetylpyridinium chloride and sodium salicylate in brine solution is investigated
through rheometric and scattering techniques. In particular, the flow and the
structural flow response are explored via velocimetry measurements and
rheological and rheometric small-angle neutron scattering (SANS) experiments,
respectively. Although all micellar solutions display a similar shear thinning
behavior in the nonlinear regime, the experimental results show that shear
banding sets in only when the micelle contour length L[over -] is sufficiently
long, independent of the nature of the micellar connections (either linear or
branched micelles). Using rheometric SANS, we observe that the shear banding
systems both show very similar orientational ordering as a function of
Weissenberg number, while the short branched micelles manifest an unexpected
increase of ordering at very low Weissenberg numbers. This suggests the presence
of an additional flow-induced relaxation process that is peculiar for branched
systems.
PMID- 28415245
TI - Converting heat into directed transport on a tilted lattice.
AB - We present a self-contained engine, which is made of one or more two-level
systems, each of which is coupled to a single bath, as well as to a common load
composed of a particle on a tilted lattice. We show that an increase in time of
energy and entropy in the system composed of the spins and the particle, due to
the interaction with the bath, can set the particle into upward motion at an
average constant speed, even when driven by a single spin connected to a single
bath. When considering an ensemble of different spins, the velocity of the
particle is larger when the tilt is on resonance with any of the spins' energy
splitting. Interestingly, we find regimes where the spins' polarization enters
periodic cycles with the oscillation period being determined by the tilt of the
lattice.
PMID- 28415246
TI - Synchronization dynamics on the picosecond time scale in coupled Josephson
junction neurons.
AB - Conventional digital computation is rapidly approaching physical limits for speed
and energy dissipation. Here we fabricate and test a simple neuromorphic circuit
that models neuronal somas, axons, and synapses with superconducting Josephson
junctions. The circuit models two mutually coupled excitatory neurons. In some
regions of parameter space the neurons are desynchronized. In others, the
Josephson neurons synchronize in one of two states, in-phase or antiphase. An
experimental alteration of the delay and strength of the connecting synapses can
toggle the system back and forth in a phase-flip bifurcation. Firing
synchronization states are calculated >70 000 times faster than conventional
digital approaches. With their speed and low energy dissipation (10^{
17}J/spike), this set of proof-of-concept experiments establishes Josephson
junction neurons as a viable approach for improvements in neuronal computation as
well as applications in neuromorphic computing.
PMID- 28415247
TI - Renormalization group analysis for an asymmetric simple exclusion process.
AB - A perturbative renormalization group method is used to obtain steady-state
density profiles of a totally asymmetric simple exclusion process with particle
adsorption and evaporation. This method allows us to obtain a globally valid
solution for the density profile without the asymptotic matching of bulk and
boundary layer solutions. In addition, we show a nontrivial scaling of the
boundary layer width with the system size close to specific phase boundaries.
PMID- 28415248
TI - Breakdown of nonlinear elasticity in stress-controlled thermal amorphous solids.
AB - In recent work it was clarified that amorphous solids under strain control do not
possess nonlinear elastic theory in the sense that the shear modulus exists but
nonlinear moduli exhibit sample-to-sample fluctuations that grow without bound
with the system size. More relevant, however, for experiments are the conditions
of stress control. In the present Rapid Communication we show that also under
stress control the shear modulus exists, but higher-order moduli show unbounded
sample-to-sample fluctuation. The unavoidable consequence is that the
characterization of stress-strain curves in experiments should be done with a
stress-dependent shear modulus rather than with nonlinear expansions.
PMID- 28415249
TI - Traveling waves and breathers in an excitatory-inhibitory neural field.
AB - We study existence and stability of traveling activity bump solutions in an
excitatory-inhibitory (E-I) neural field with Heaviside firing rate functions by
deriving existence conditions for traveling bumps and an Evans function to
analyze their spectral stability. Subsequently, we show that these existence and
stability results reduce, in the limit of wave speed c->0, to the equivalent
conditions developed for the stationary bump case. Using the results for the
stationary bump case, we show that drift bifurcations of stationary bumps serve
as a mechanism for generating traveling bump solutions in the E-I neural field as
parameters are varied. Furthermore, we explore the interrelations between
stationary and traveling types of bumps and breathers (time-periodic oscillatory
bumps) by bridging together analytical and simulation results for stationary and
traveling bumps and their bifurcations in a region of parameter space.
Interestingly, we find evidence for a codimension-2 drift-Hopf bifurcation
occurring as two parameters, inhibitory time constant tau and I-to-I synaptic
connection strength w[over -]_{ii}, are varied and show that the codimension-2
point serves as an organizing center for the dynamics of these four types of
spatially localized solutions. Additionally, we describe a case involving
subcritical bifurcations that lead to traveling waves and breathers as tau is
varied.
PMID- 28415250
TI - Compressible cell gas models for asymmetric fluid criticality.
AB - We thoroughly describe a class of models recently presented by Fisher and
coworkers [Phys. Rev. Lett. 116, 040601 (2016)]PRLTAO0031
900710.1103/PhysRevLett.116.040601. The crucial feature of such models, termed
compressible cell gases (CCGs), is that the individual cell volumes of a lattice
gas are allowed to fluctuate. They are studied via the seldom-used (MU, p, T)
ensemble, which leads to their exact mapping onto the Ising model. Remarkably,
CCGs obey complete scaling, a formulation for the thermodynamic behavior of
fluids near the gas-liquid critical point that accommodates features inherent to
the asymmetric nature of this phase transition like the Yang-Yang (YY) and
singular coexistence-curve diameter anomalies. The CCG_{0} models generated when
volumes vary freely reveal local free volume fluctuations as the origin of these
phenomena. Local energy-volume coupling is found to be another relevant
microscopic factor. Furthermore, the CCG class is greatly extended by using the
decoration transformation, with an interesting example being the Sastry
Debenedetti-Sciortino-Stanley model for hydrogen bonding in low-temperature
water. The magnitude of anomalies is characterized by a single parameter, the YY
ratio, which for the models so far considered here ranges from -infinity to 1/2.
PMID- 28415251
TI - Velocity distribution of a driven inelastic one-component Maxwell gas.
AB - The nature of the velocity distribution of a driven granular gas, though well
studied, is unknown as to whether it is universal or not, and, if universal, what
it is. We determine the tails of the steady state velocity distribution of a
driven inelastic Maxwell gas, which is a simple model of a granular gas where the
rate of collision between particles is independent of the separation as well as
the relative velocity. We show that the steady state velocity distribution is
nonuniversal and depends strongly on the nature of driving. The asymptotic
behavior of the velocity distribution is shown to be identical to that of a
noninteracting model where the collisions between particles are ignored. For
diffusive driving, where collisions with the wall are modeled by an additive
noise, the tails of the velocity distribution is universal only if the noise
distribution decays faster than exponential.
PMID- 28415252
TI - Clogging and jamming transitions in periodic obstacle arrays.
AB - We numerically examine clogging transitions for bidisperse disks flowing through
a two-dimensional periodic obstacle array. We show that clogging is a
probabilistic event that occurs through a transition from a homogeneous flowing
state to a heterogeneous or phase-separated jammed state where the disks form
dense connected clusters. The probability for clogging to occur during a fixed
time increases with increasing particle packing and obstacle number. For driving
at different angles with respect to the symmetry direction of the obstacle array,
we show that certain directions have a higher clogging susceptibility. It is also
possible to have a size-specific clogging transition in which one disk size
becomes completely immobile while the other disk size continues to flow.
PMID- 28415253
TI - Nonequilibrium random matrix theory: Transition probabilities.
AB - In this paper we present an analytic method for calculating the transition
probability between two random Gaussian matrices with given eigenvalue spectra in
the context of Dyson Brownian motion. We show that in the Coulomb gas language,
in large N limit, memory of the initial state is preserved in the form of a
universal linear potential acting on the eigenvalues. We compute the likelihood
of any given transition as a function of time, showing that as memory of the
initial state is lost, transition probabilities converge to those of the static
ensemble.
PMID- 28415254
TI - Anomalous diffusion in viscoelastic media with active force dipoles.
AB - With the use of the "two-fluid model," we discuss anomalous diffusion induced by
active force dipoles in viscoelastic media. Active force dipoles, such as
proteins and bacteria, generate nonthermal fluctuating flows that lead to a
substantial increment of the diffusion. Using the partial Green's function of the
two-fluid model, we first obtain passive (thermal) two-point correlation
functions such as the displacement cross-correlation function between the two
point particles separated by a finite distance. We then calculate active
(nonthermal) one-point and two-point correlation functions due to active force
dipoles. The time correlation of a force dipole is assumed to decay exponentially
with a characteristic time scale. We show that the active component of the
displacement cross-correlation function exhibits various crossovers from super
diffusive to subdiffusive behaviors depending on the characteristic time scales
and the particle separation. Our theoretical results are intimately related to
the microrheology technique to detect fluctuations in nonequilibrium environment.
PMID- 28415255
TI - Numerical study of one-dimensional compression of granular materials. I. Stress
strain behavior, microstructure, and irreversibility.
AB - The behavior of a model granular material, made of slightly polydisperse beads
with Hertz-Mindlin elastic-frictional contacts, in oedometric compression (i.e.,
compression along one axis, with no lateral strain) is studied by grain-level
numerical simulations. We systematically investigate the influence of the
(idealized) packing process on the microstructure and stresses in the initial,
weakly confined equilibrium state, and prepare both isotropic and anisotropic
configurations differing in solid fraction Phi and coordination number z. Phi
(ranging from maximally dense to moderately loose), z (which might vary
independently of Phi in dense systems), fabric and force anisotropy parameters,
and the ratio K_{0} of lateral stresses sigma_{2}=sigma_{3} to stress sigma_{1}
in the compression direction are monitored in oedometric compression in which
sigma_{1} varies by more than three orders of magnitude. K_{0} reflects the
anisotropy of the assembling process and may remain nearly constant in further
loading if the material is already oedometrically compressed (as a granular gas)
in the preparation stage. Otherwise, it tends to decrease steadily over the
investigated stress range. It is related to force and fabric anisotropy
parameters by a simple formula. Elastic moduli, separately computed with an
appropriate matrix method, may express the response to very small stress
increments about the transversely isotropic well-equilibrated states along the
loading path, although oedometric compression proves an essentially anelastic
process, mainly due to friction mobilization, with large irreversible effects
apparent upon unloading. While the evolution of axial strain epsilon_{1} and
solid fraction Phi (or of the void ratio e=-1+1/Phi) with axial stress sigma_{1}
is very nearly reversible, especially in dense samples, z is observed to decrease
(as previously observed in isotropic compression) after a compression cycle if
its initial value was high. K_{0} relates to the evolution of internal variables
and may exceed 1 in unloading. The considerably greater irreversibility of
oedometric compression reported in sands, compared to our model systems, should
signal contact plasticity or damage.
PMID- 28415256
TI - Turbulent compressible fluid: Renormalization group analysis, scaling regimes,
and anomalous scaling of advected scalar fields.
AB - We study a model of fully developed turbulence of a compressible fluid, based on
the stochastic Navier-Stokes equation, by means of the field-theoretic
renormalization group. In this approach, scaling properties are related to the
fixed points of the renormalization group equations. Previous analysis of this
model near the real-world space dimension 3 identified a scaling regime [N. V.
Antonov et al., Theor. Math. Phys. 110, 305 (1997)TMPHAH0040
577910.1007/BF02630456]. The aim of the present paper is to explore the existence
of additional regimes, which could not be found using the direct perturbative
approach of the previous work, and to analyze the crossover between different
regimes. It seems possible to determine them near the special value of space
dimension 4 in the framework of double y and E expansion, where y is the exponent
associated with the random force and E=4-d is the deviation from the space
dimension 4. Our calculations show that there exists an additional fixed point
that governs scaling behavior. Turbulent advection of a passive scalar (density)
field by this velocity ensemble is considered as well. We demonstrate that
various correlation functions of the scalar field exhibit anomalous scaling
behavior in the inertial-convective range. The corresponding anomalous exponents,
identified as scaling dimensions of certain composite fields, can be
systematically calculated as a series in y and E. All calculations are performed
in the leading one-loop approximation.
PMID- 28415257
TI - Effect of single-particle magnetostriction on the shear modulus of compliant
magnetoactive elastomers.
AB - The influence of an external magnetic field on the static shear strain and the
effective shear modulus of a magnetoactive elastomer (MAE) is studied
theoretically in the framework of a recently introduced approach to the single
particle magnetostriction mechanism [V. M. Kalita et al., Phys. Rev. E 93, 062503
(2016)10.1103/PhysRevE.93.062503]. The planar problem of magnetostriction in an
MAE with magnetically soft inclusions in the form of a thin disk (platelet)
having the magnetic anisotropy in the plane of this disk is solved analytically.
An external magnetic field acts with torques on magnetic filler particles,
creates mechanical stresses in the vicinity of inclusions, induces shear strain,
and increases the effective shear modulus of these composite materials. It is
shown that the largest effect of the magnetic field on the effective shear
modulus should be expected in MAEs with soft elastomer matrices, where the shear
modulus of the matrix is less than the magnetic anisotropy constant of
inclusions. It is derived that the effective shear modulus is nonlinearly
dependent on the external magnetic field and approaches the saturation value in
magnetic fields exceeding the field of particle anisotropy. It is shown that
model calculations of the effective shear modulus correspond to a
phenomenological definition of effective elastic moduli and magnetoelastic
coupling constants. The obtained theoretical results compare well with known
experimental data. Determination of effective elastic coefficients in MAEs and
their dependence on magnetic field is discussed. The concentration dependence of
the effective shear modulus at higher filler concentrations has been estimated
using the method of Pade approximants, which predicts that both the absolute and
relative changes of the magnetic-field-dependent effective shear modulus will
significantly increase with the growing concentration of filler particles.
PMID- 28415258
TI - Fluctuations around mean walking behaviors in diluted pedestrian flows.
AB - Understanding and modeling the dynamics of pedestrian crowds can help with
designing and increasing the safety of civil facilities. A key feature of a crowd
is its intrinsic stochasticity, appearing even under very diluted conditions, due
to the variability in individual behaviors. Individual stochasticity becomes even
more important under densely crowded conditions, since it can be nonlinearly
magnified and may lead to potentially dangerous collective behaviors. To
understand quantitatively crowd stochasticity, we study the real-life dynamics of
a large ensemble of pedestrians walking undisturbed, and we perform a statistical
analysis of the fully resolved pedestrian trajectories obtained by a yearlong
high-resolution measurement campaign. Our measurements have been carried out in a
corridor of the Eindhoven University of Technology via a combination of Microsoft
Kinect 3D range sensor and automatic head-tracking algorithms. The temporal
homogeneity of our large database of trajectories allows us to robustly define
and separate average walking behaviors from fluctuations parallel and orthogonal
with respect to the average walking path. Fluctuations include rare events when
individuals suddenly change their minds and invert their walking directions. Such
tendency to invert direction has been poorly studied so far, even if it may have
important implications on the functioning and safety of facilities. We propose a
model for the dynamics of undisturbed pedestrians, based on stochastic
differential equations, that provides a good agreement with our field
observations, including the occurrence of rare events.
PMID- 28415259
TI - Effects of disorder and chain stiffening on the elasticity of flexible polymer
networks.
AB - We examine how the distribution of contour lengths and the high-stretch
stiffening of individual chain segments affect the macroscopic shear modulus of
flexible polymer gels, using a two-dimensional numerical model in which polymer
segments form a triangular network and disorder is introduced by varying their
contour lengths. We show that, in the relevant parameter range: (i) the nonaffine
contribution to the shear modulus is negligible, i.e., the Born approximation is
satisfactory, and (ii) the shear modulus is dominated by the contribution
originating from equilibrium chain tensions. Moreover, mechanical equilibration
at the nodes induces specific correlations between the end-to-end distances and
contour lengths of chain segments, which must be properly accounted for to
construct reasonable estimates of chain pressure and shear modulus.
PMID- 28415260
TI - Enhanced processing in arrays of optimally tuned nonlinear biomimetic sensors: A
coupling-mediated Ringelmann effect and its dynamical mitigation.
AB - Inspired by recent results on self-tunability in the outer hair cells of the
mammalian cochlea, we describe an array of magnetic sensors where each individual
sensor can self-tune to an optimal operating regime. The self-tuning gives the
array its "biomimetic" features. We show that the overall performance of the
array can, as expected, be improved by increasing the number of sensors but,
however, coupling between sensors reduces the overall performance even though the
individual sensors in the system could see an improvement. We quantify the
similarity of this phenomenon to the Ringelmann effect that was formulated 103
years ago to account for productivity losses in human and animal groups. We
propose a global feedback scheme that can be used to greatly mitigate the
performance degradation that would, normally, stem from the Ringelmann effect.
PMID- 28415261
TI - Robustness of spatial patterns in buffered reaction-diffusion systems and its
reciprocity with phase plasticity.
AB - The robustness of spatial patterns against perturbations is an indispensable
property of developmental processes for organisms, which need to adapt to
changing environments. Although specific mechanisms for this robustness have been
extensively investigated, little is known about a general mechanism for achieving
robustness in reaction-diffusion systems. Here, we propose a buffered reaction
diffusion system, in which active states of chemicals mediated by buffer
molecules contribute to reactions, and demonstrate that robustness of the pattern
wavelength is achieved by the dynamics of the buffer molecule. This robustness is
analytically explained as a result of the scaling properties of the buffered
system, which also lead to a reciprocal relationship between the wavelength's
robustness and the plasticity of the spatial phase upon external perturbations.
Finally, we explore the relevance of this reciprocity to biological systems.
PMID- 28415262
TI - Thermophoretic force on nanocylinders in the free molecule regime.
AB - We theoretically investigate the thermophoresis of nanocylinders in the free
molecule regime, wherein the nonrigid-body effect is taken into account. The
analytical formulas of the thermophoretic forces on cylinders suspended in both
simple gases and binary gas mixtures are derived for the two limiting collision
models, i.e., specular and diffuse scatterings, based on the gas kinetic theory.
In the limit of the rigid-body collision, the expressions can be reduced to the
theoretical results of Garcia-Ybarra and Rosner [AIChE J. 35, 139
(1989)10.1002/aic.690350115]. The thermophoretic velocities of the nanocylinders
(including carbon nanotubes and long-chain n-alkanes) have been evaluated and it
is found that the influence of the nonrigid-body effect on thermophoresis is
significant for the case of small cylinder radius and low temperatures.
PMID- 28415263
TI - Percolation on networks with weak and heterogeneous dependency.
AB - In real networks, the dependency between nodes is ubiquitous; however, the
dependency is not always complete and homogeneous. In this paper, we propose a
percolation model with weak and heterogeneous dependency; i.e., dependency
strengths could be different between different nodes. We find that the
heterogeneous dependency strength will make the system more robust, and for
various distributions of dependency strengths both continuous and discontinuous
percolation transitions can be found. For Erdos-Renyi networks, we prove that the
crossing point of the continuous and discontinuous percolation transitions is
dependent on the first five moments of the dependency strength distribution. This
indicates that the discontinuous percolation transition on networks with
dependency is determined not only by the dependency strength but also by its
distribution. Furthermore, in the area of the continuous percolation transition,
we also find that the critical point depends on the first and second moments of
the dependency strength distribution. To validate the theoretical analysis, cases
with two different dependency strengths and Gaussian distribution of dependency
strengths are presented as examples.
PMID- 28415264
TI - Self-energy matrices for electron transport calculations within the real-space
finite-difference formalism.
AB - The self-energy term used in transport calculations, which describes the coupling
between electrode and transition regions, is able to be evaluated only from a
limited number of the propagating and evanescent waves of a bulk electrode. This
obviously contributes toward the reduction of the computational expenses in
transport calculations. In this paper, we present a mathematical formula for
reducing the computational expenses further without using any approximation and
without losing accuracy. So far, the self-energy term has been handled as a
matrix with the same dimension as the Hamiltonian submatrix representing the
interaction between an electrode and a transition region. In this work, through
the singular-value decomposition of the submatrix, the self-energy matrix is
handled as a smaller matrix, whose dimension is the rank number of the
Hamiltonian submatrix. This procedure is practical in the case of using the
pseudopotentials in a separable form, and the computational expenses for
determining the self-energy matrix are reduced by 90% when employing a code based
on the real-space finite-difference formalism and projector-augmented wave
method. In addition, this technique is applicable to the transport calculations
using atomic or localized basis sets. Adopting the self-energy matrices obtained
from this procedure, we present the calculation of the electron transport
properties of C_{20} molecular junctions. The application demonstrates that the
electron transmissions are sensitive to the orientation of the molecule with
respect to the electrode surface. In addition, channel decomposition of the
scattering wave functions reveals that some unoccupied C_{20} molecular orbitals
mainly contribute to the electron conduction through the molecular junction.
PMID- 28415265
TI - Comparative statistics of selected subgrid-scale models in large-eddy simulations
of decaying, supersonic magnetohydrodynamic turbulence.
AB - Large-eddy simulations (LES) are a powerful tool in understanding processes that
are inaccessible by direct simulations due to their complexity, for example, in
the highly turbulent regime. However, their accuracy and success depends on a
proper subgrid-scale (SGS) model that accounts for the unresolved scales in the
simulation. We evaluate the applicability of two traditional SGS models, namely
the eddy-viscosity (EV) and the scale-similarity (SS) models, and one recently
proposed nonlinear (NL) SGS model in the realm of compressible
magnetohydrodynamic (MHD) turbulence. Using 209 simulations of decaying,
supersonic (initial sonic Mach number M_{s}~3) MHD turbulence with a shock
capturing scheme and varying resolution, SGS model, and filter, we analyze the
ensemble statistics of kinetic and magnetic energy spectra and structure
functions. Furthermore, we compare the temporal evolution of lower- and higher
order statistical moments of the spatial distributions of kinetic and magnetic
energy, vorticity, current density, and dilatation magnitudes. We find no
statistical influence on the evolution of the flow by any model if grid-scale
quantities are used to calculate SGS contributions. In addition, the SS models,
which employ an explicit filter, have no impact in general. On the contrary, both
the EV and NL models change the statistics if an explicit filter is used. For
example, they slightly increase the dissipation on the smallest scales. We
demonstrate that the nonlinear model improves higher-order statistics already
with a small explicit filter, i.e., a three-point stencil. The results of, e.g.,
the structure functions or the skewness and kurtosis of the current density
distribution are closer to the ones obtained from simulations at higher
resolution. In addition, no additional regularization to stabilize the model is
required. We conclude that the nonlinear model with a small explicit filter is
suitable for application in more complex scenarios when higher-order statistics
are important.
PMID- 28415266
TI - Cavitation and spallation in liquid metal droplets produced by subpicosecond
pulsed laser radiation.
AB - The deformation and fragmentation of liquid metal microdroplets by intense
subpicosecond Ti:sapphire laser pulses is experimentally studied with
stroboscopic shadow photography. The experiments are performed at a peak
intensity of 10^{14}W/cm^{2} at the target's surface, which produces shock waves
with pressures in the Mbar range. As a result of such a strong impact, the
droplet is transformed into a complex-shaped hollow structure that undergoes
asymmetrical expansion and eventually fragments. The hollow structure of the
expanding target is explained by the effects of cavitation and spallation that
follow the propagation of the laser-induced shock wave.
PMID- 28415267
TI - Dispersion relation for electromagnetic propagation in stochastic dielectric and
magnetic helical photonic crystals.
AB - We theoretically study the dispersion relation for axially propagating
electromagnetic waves throughout a one-dimensional helical structure whose pitch
and dielectric and magnetic properties are spatial random functions with specific
statistical characteristics. In the system of coordinates rotating with the
helix, by using a matrix formalism, we write the set of differential equations
that governs the expected value of the electromagnetic field amplitudes and we
obtain the corresponding dispersion relation. We show that the dispersion
relation depends strongly on the noise intensity introduced in the system and the
autocorrelation length. When the autocorrelation length increases at fixed
fluctuation and when the fluctuation augments at fixed autocorrelation length,
the band gap widens and the attenuation coefficient of electromagnetic waves
propagating in the random medium gets larger. By virtue of the degeneracy in the
imaginary part of the eigenvalues associated with the propagating modes, the
random medium acts as a filter for circularly polarized electromagnetic waves, in
which only the propagating backward circularly polarized wave can propagate with
no attenuation. Our results are valid for any kind of dielectric and magnetic
structures which possess a helical-like symmetry such as cholesteric and chiral
smectic-C liquid crystals, structurally chiral materials, and stressed
cholesteric elastomers.
PMID- 28415268
TI - Delayed collapses of Bose-Einstein condensates in relation to anti-de Sitter
gravity.
AB - We numerically investigate spherically symmetric collapses in the Gross
Pitaevskii equation with attractive nonlinearity in a harmonic potential. Even
below threshold for direct collapse, the wave function bounces off from the
origin and may eventually become singular after a number of oscillations in the
trapping potential. This is reminiscent of the evolution of Einstein gravity
sourced by a scalar field in anti de Sitter space where collapse corresponds to
black-hole formation. We carefully examine the long time evolution of the wave
function for continuous families of initial states in order to sharpen out this
qualitative coincidence which may bring new insights in both directions. On the
one hand, we comment on possible implications for the so-called Bosenova
collapses in cold atom Bose-Einstein condensates. On the other hand, Gross
Pitaevskii provides a toy model to study the relevance of either the resonance
conditions or the nonlinearity for the problem of anti de Sitter instability.
PMID- 28415269
TI - Relevant parameters in models of cell division control.
AB - A recent burst of dynamic single-cell data makes it possible to characterize the
stochastic dynamics of cell division control in bacteria. Different models were
used to propose specific mechanisms, but the links between them are poorly
explored. The lack of comparative studies makes it difficult to appreciate how
well any particular mechanism is supported by the data. Here, we describe a
simple and generic framework in which two common formalisms can be used
interchangeably: (i) a continuous-time division process described by a hazard
function and (ii) a discrete-time equation describing cell size across
generations (where the unit of time is a cell cycle). In our framework, this
second process is a discrete-time Langevin equation with simple physical
analogues. By perturbative expansion around the mean initial size (or
interdivision time), we show how this framework describes a wide range of
division control mechanisms, including combinations of time and size control, as
well as the constant added size mechanism recently found to capture several
aspects of the cell division behavior of different bacteria. As we show by
analytical estimates and numerical simulations, the available data are described
precisely by the first-order approximation of this expansion, i.e., by a "linear
response" regime for the correction of size fluctuations. Hence, a single
dimensionless parameter defines the strength and action of the division control
against cell-to-cell variability (quantified by a single "noise" parameter).
However, the same strength of linear response may emerge from several mechanisms,
which are distinguished only by higher-order terms in the perturbative expansion.
Our analytical estimate of the sample size needed to distinguish between second
order effects shows that this value is close to but larger than the values of the
current datasets. These results provide a unified framework for future studies
and clarify the relevant parameters at play in the control of cell division.
PMID- 28415270
TI - Pinning of scroll waves to flat and highly branched unexcitable heterogeneities.
AB - System heterogeneities such as organelles, cells, and anatomical features
strongly affect nonlinear wave patterns in biological systems. These effects are
more readily studied in otherwise homogeneous chemical reactions that allow the
introduction of tailored structures. Following this approach, we investigate the
dynamics of three-dimensional excitation vortices pinned to inert sheets with
circular holes arranged on a hexagonal lattice. Experiments with the Belousov
Zhabotinsky reaction and numerical simulations of an excitable reaction-diffusion
model reveal vortex pinning that circumvents the rapid collapse of free vortex
rings. The pinned scroll waves are affected by the topological mismatch between
their looplike rotation backbone and the branched pinning structure. Depending on
the initial condition, a multitude of stable vortex states exist, all of which
obey topological constraints, suggesting spinlike states for the involved
obstacle holes.
PMID- 28415271
TI - Mean-cluster approach indicates cell sorting time scales are determined by
collective dynamics.
AB - Cell migration is essential to cell segregation, playing a central role in tissue
formation, wound healing, and tumor evolution. Considering random mixtures of two
cell types, it is still not clear which cell characteristics define clustering
time scales. The mass of diffusing clusters merging with one another is expected
to grow as t^{d/d+2} when the diffusion constant scales with the inverse of the
cluster mass. Cell segregation experiments deviate from that behavior.
Explanations for that could arise from specific microscopic mechanisms or from
collective effects, typical of active matter. Here we consider a power law
connecting diffusion constant and cluster mass to propose an analytic approach to
model cell segregation where we explicitly take into account finite-size
corrections. The results are compared with active matter model simulations and
experiments available in the literature. To investigate the role played by
different mechanisms we considered different hypotheses describing cell-cell
interaction: differential adhesion hypothesis and different velocities
hypothesis. We find that the simulations yield normal diffusion for long time
intervals. Analytic and simulation results show that (i) cluster evolution
clearly tends to a scaling regime, disrupted only at finite-size limits; (ii)
cluster diffusion is greatly enhanced by cell collective behavior, such that for
high enough tendency to follow the neighbors, cluster diffusion may become
independent of cluster size; (iii) the scaling exponent for cluster growth
depends only on the mass-diffusion relation, not on the detailed local
segregation mechanism. These results apply for active matter systems in general
and, in particular, the mechanisms found underlying the increase in cell sorting
speed certainly have deep implications in biological evolution as a selection
mechanism.
PMID- 28415272
TI - Effect of node attributes on the temporal dynamics of network structure.
AB - Many natural and social networks evolve in time and their structures are dynamic.
In most networks, nodes are heterogeneous, and their roles in the evolution of
structure differ. This paper focuses on the role of individual attributes on the
temporal dynamics of network structure. We focus on a basic model for growing
networks that incorporates node attributes (which we call "quality"), and we
focus on the problem of forecasting the structural properties of the network in
arbitrary times for an arbitrary initial network. That is, we address the
following question: If we are given a certain initial network with given
arbitrary structure and known node attributes, then how does the structure change
in time as new nodes with given distribution of attributes join the network? We
solve the model analytically and obtain the quality-degree joint distribution and
degree correlations. We characterize the role of individual attributes in the
position of individual nodes in the hierarchy of connections. We confirm the
theoretical findings with Monte Carlo simulations.
PMID- 28415273
TI - Theory of deflagration in disordered media.
AB - The conventional theory of burning works well in the case of uniform media where
all system parameters are spatially independent. We develop a theory of burning
in disordered media. In this case, rare regions (hot spots) where the burning
process is more effective than on average may control the heat propagation in an
explosive sample. We show that most predictions of the theory of burning are
quite different from the conventional case. In particular, we show that a system
of randomly distributed hot spots exhibits a dynamic phase transition, which is
similar to the percolation transition. Depending on parameters of the system the
phase transition can be either first or second order. These two regimes are
separated by a tricritical point. The above results may be applicable to dynamics
of any overheated disordered system with a first order phase transition.
PMID- 28415274
TI - Earliest effects of sudden occlusions on pressure profiles in selected locations
of the human systemic arterial system.
AB - We have developed a numerical simulation method for predicting the time
dependence (wave form) of pressure at any location in the systemic arterial
system in humans. The method uses the matlab-Simulink environment. The input data
include explicitly the geometry of the arterial tree, treated up to an arbitrary
bifurcation level, and the elastic properties of arteries as well as rheological
parameters of blood. Thus, the impact of anatomic details of an individual
subject can be studied. The method is applied here to reveal the earliest stages
of mechanical reaction of the pressure profiles to sudden local blockages
(thromboses or embolisms) of selected arteries. The results obtained with a
purely passive model provide reference data indispensable for studies of longer
term effects due to neural and humoral mechanisms. The reliability of the results
has been checked by comparison of two available sets of anatomic, elastic, and
rheological data involving (i) 55 and (ii) 138 arterial segments. The remaining
arteries have been replaced with the appropriate resistive elements. Both models
are efficient in predicting an overall shift of pressure, whereas the accuracy of
the 55-segment model in reproducing the detailed wave forms and stabilization
times turns out dependent on the location of the blockage and the observation
point.
PMID- 28415275
TI - Effects of surface roughness on shear viscosity.
AB - This paper investigates the effect of surface roughness on fluid viscosity using
molecular dynamics simulations. The three-dimensional model consists of liquid
argon flowing between two solid walls whose surface roughness was modeled using
fractal theory. In tandem with previously published experimental work, our
results show that, while the viscosity in smooth channels remains constant across
the channel width, in the presence of surface roughness it increases close to the
walls. The increase of the boundary viscosity is further accentuated by an
increase in the depth of surface roughness. We attribute this behavior to the
increased momentum transfer at the boundary, a result of the irregular
distribution of fluid particles near rough surfaces. Furthermore, although the
viscosity in smooth channels has previously been shown to be independent of the
strength of the solid-liquid interaction, here we show that in the presence of
surface roughness, the boundary viscosity increases with the solid's wettability.
The paper concludes with an analytical description of the viscosity as a function
of the distance from the channel walls, the walls' surface roughness, and the
solid's wetting properties. The relation can potentially be used to adjust the
fluid dynamics equations for a more accurate description of microfluidic systems.
PMID- 28415276
TI - Transition of multidiffusive states in a biased periodic potential.
AB - We study a frequency-dependent damping model of hyperdiffusion within the
generalized Langevin equation. The model allows for the colored noise defined by
its spectral density, assumed to be proportional to omega^{delta-1} at low
frequencies with 01 noncrossing continuum DP in a random potential, to the sum of the
Nth largest eigenvalues of the GUE. Here, using replica methods, we provide an
important test of this conjecture by calculating exactly the right tails of both
PDFs and showing that they coincide for arbitrary N.
PMID- 28415281
TI - Stochastic dynamics and the predictability of big hits in online videos.
AB - The competition for the attention of users is a central element of the Internet.
Crucial issues are the origin and predictability of big hits, the few items that
capture a big portion of the total attention. We address these issues analyzing
10^{6} time series of videos' views from YouTube. We find that the average gain
of views is linearly proportional to the number of views a video already has, in
agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails
to explain the prevalence of big hits. The reason is that the fluctuations around
the average views are themselves heavy tailed. Based on these empirical
observations, we propose a stochastic differential equation with Levy noise as a
model of the dynamics of videos. We show how this model is substantially better
in estimating the probability of an ordinary item becoming a big hit, which is
considerably underestimated in the traditional proportional-growth models.
PMID- 28415282
TI - Traction reveals mechanisms of wall effects for microswimmers near boundaries.
AB - The influence of a plane boundary on low-Reynolds-number swimmers has frequently
been studied using image systems for flow singularities. However, the boundary
effect can also be expressed using a boundary integral representation over the
traction on the boundary. We show that examining the traction pattern on the
boundary caused by a swimmer can yield physical insights into determining when
far-field multipole models are accurate. We investigate the swimming velocities
and the traction of a three-sphere swimmer initially placed parallel to an
infinite planar wall. In the far field, the instantaneous effect of the wall on
the swimmer is well approximated by that of a multipole expansion consisting of a
force dipole and a force quadrupole. On the other hand, the swimmer close to the
wall must be described by a system of singularities reflecting its internal
structure. We show that these limits and the transition between them can be
independently identified by examining the traction pattern on the wall, either
using a quantitative correlation coefficient or by visual inspection. Last, we
find that for nonconstant propulsion, correlations between swimming stroke
motions and internal positions are important and not captured by time-averaged
traction on the wall, indicating that care must be taken when applying multipole
expansions to study boundary effects in cases of nonconstant propulsion.
PMID- 28415283
TI - Quantifying disorder in colloidal films spin-coated onto patterned substrates.
AB - Polycrystals of thin colloidal deposits, with thickness controlled by spin
coating speed, exhibit axial symmetry with local 4-fold and 6-fold symmetric
structures, termed orientationally correlated polycrystals (OCPs). While spin
coating is a very facile technique for producing large-area colloidal deposits,
the axial symmetry prevents us from achieving true long-range order. To obtain
true long-range order, we break this axial symmetry by introducing a patterned
surface topography and thus eliminate the OCP character. We then examine symmetry
independent methods to quantify order in these disordered colloidal deposits. We
find that all the information in the bond-orientational order parameters is well
captured by persistent homology analysis methods that only use the centers of the
particles as input data. It is expected that these methods will prove useful in
characterizing other disordered structures.
PMID- 28415284
TI - Theory of linear sweep voltammetry with diffuse charge: Unsupported electrolytes,
thin films, and leaky membranes.
AB - Linear sweep and cyclic voltammetry techniques are important tools for
electrochemists and have a variety of applications in engineering. Voltammetry
has classically been treated with the Randles-Sevcik equation, which assumes an
electroneutral supported electrolyte. In this paper, we provide a comprehensive
mathematical theory of voltammetry in electrochemical cells with unsupported
electrolytes and for other situations where diffuse charge effects play a role,
and present analytical and simulated solutions of the time-dependent Poisson
Nernst-Planck equations with generalized Frumkin-Butler-Volmer boundary
conditions for a 1:1 electrolyte and a simple reaction. Using these solutions, we
construct theoretical and simulated current-voltage curves for liquid and solid
thin films, membranes with fixed background charge, and cells with blocking
electrodes. The full range of dimensionless parameters is considered, including
the dimensionless Debye screening length (scaled to the electrode separation),
Damkohler number (ratio of characteristic diffusion and reaction times), and
dimensionless sweep rate (scaled to the thermal voltage per diffusion time). The
analysis focuses on the coupling of Faradaic reactions and diffuse charge
dynamics, although capacitive charging of the electrical double layers is also
studied, for early time transients at reactive electrodes and for nonreactive
blocking electrodes. Our work highlights cases where diffuse charge effects are
important in the context of voltammetry, and illustrates which regimes can be
approximated using simple analytical expressions and which require more careful
consideration.
PMID- 28415285
TI - Ellipsoidal Brownian self-driven particles in a magnetic field.
AB - We study the two-dimensional Brownian dynamics of an ellipsoidal paramagnetic
microswimmer moving at a low Reynolds number and subject to a magnetic field. Its
corresponding mean-square displacement, showing the effect of a particles's
shape, activity, and magnetic field on the microswimmer's diffusion, is
analytically obtained. Comparison between analytical and computational results
shows good agreement. In addition, the effect of self-propulsion on the
transition time from anisotropic to isotropic diffusion of the ellipse is
investigated.
PMID- 28415286
TI - Dissociation between two subgroups of the suprachiasmatic nucleus affected by the
number of damped oscillated neurons.
AB - In mammals, the main clock located in the suprachiasmatic nucleus (SCN) of the
brain synchronizes the body rhythms to the environmental light-dark cycle. The
SCN is composed of about 2*10^{4} neurons which can be classified into three
oscillatory phenotypes: self-sustained oscillators, damped oscillators, and
arrhythmic neurons. Exposed to an artificial external light-dark cycle with a
period of 22h instead of 24h, two subgroups of the SCN can become desynchronized
(dissociated). The ventrolateral (VL) subgroup receives photic input and is
entrained to the external cycle and a dorsomedial (DM) subgroup oscillates with
its endogenous (i.e., free running) period and is synchronized to the external
light-dark cycle through coupling from the VL. In the present study, we examined
the effects of damped oscillatory neurons on the dissociation between VL and DM
under an external 22h cycle. We found that, with increasing numbers of damped
oscillatory neurons located in the VL, the dissociation between the VL and DM
emerges, but if these neurons are increasingly present in the DM the dissociation
disappears. Hence, the damped oscillatory neurons in different subregions of the
SCN play distinct roles in the dissociation between the two subregions of the
SCN. This shows that synchrony between SCN subregions is affected by the number
of damped oscillatory neurons and the location of these cells. We suggest that
more knowledge on the number and the location of these cells may explain why some
species do show a dissociation between the subregions and others do not, as the
distribution of oscillatory types of neurons offers a plausible and novel
candidate mechanism to explain heterogeneity.
PMID- 28415287
TI - Effect of interstitial fluid on the fraction of flow microstates that precede
clogging in granular hoppers.
AB - We report on the nature of flow events for the gravity-driven discharge of glass
beads through a hole that is small enough that the hopper is susceptible to
clogging. In particular, we measure the average and standard deviation of the
distribution of discharged masses as a function of both hole and grain sizes. We
do so in air, which is usual, but also with the system entirely submerged under
water. This damps the grain dynamics and could be expected to dramatically affect
the distribution of the flow events, which are described in prior work as
avalanche-like. Though the flow is slower and the events last longer, we find
that the average discharge mass is only slightly reduced for submerged grains.
Furthermore, we find that the shape of the distribution remains exponential,
implying that clogging is still a Poisson process even for immersed grains. Per
Thomas and Durian [Phys. Rev. Lett. 114, 178001 (2015)PRLTAO0031
900710.1103/PhysRevLett.114.178001], this allows for an interpretation of the
average discharge mass in terms of the fraction of flow microstates that precede,
i.e., that effectively cause, a stable clog to form. Since this fraction is
barely altered by water, we conclude that the crucial microscopic variables are
the grain positions; grain momenta play only a secondary role in destabilizing
weak incipient arches. These insights should aid ongoing efforts to understand
the susceptibility of granular hoppers to clogging.
PMID- 28415288
TI - Foraging patterns in online searches.
AB - Nowadays online searches are undeniably the most common form of information
gathering, as witnessed by billions of clicks generated each day on search
engines. In this work we describe online searches as foraging processes that take
place on the semi-infinite line. Using a variety of quantities like probability
distributions and complementary cumulative distribution functions of step length
and waiting time as well as mean square displacements and entropies, we analyze
three different click-through logs that contain the detailed information of
millions of queries submitted to search engines. Notable differences between the
different logs reveal an increased efficiency of the search engines. In the
language of foraging, the newer logs indicate that online searches overwhelmingly
yield local searches (i.e., on one page of links provided by the search engines),
whereas for the older logs the foraging processes are a combination of local
searches and relocation phases that are power law distributed. Our investigation
of click logs of search engines therefore highlights the presence of intermittent
search processes (where phases of local explorations are separated by power law
distributed relocation jumps) in online searches. It follows that good search
engines enable the users to find the information they are looking for through a
local exploration of a single page with search results, whereas for poor search
engine users are often forced to do a broader exploration of different pages.
PMID- 28415289
TI - Shear transformation distribution and activation in glasses at the atomic scale.
AB - We characterize shear transformations (STs) at the atomic scale in a model of
amorphous silicon using a mapping on Eshelby inclusions. We investigate the
effect of pressure, glass relaxation, as well as damage on the ST
characteristics. We show that the characteristic ST effective volume,
gamma_{0}V_{0}, product of the ST plastic shear strain gamma_{0} and volume
V_{0}, does not depend significantly on an applied pressure but increases with
accumulated plastic deformation from about 10A^{3} in the pseudoelastic regime to
about 60A^{3} once plastic flow sets in. Furthermore, by using nudged elastic
band calculations, we measure the energy barrier against ST activation. Analyzing
different paths leading to either an isolated ST or an avalanche, we show that
the barrier is systematically controlled by the first ST with an activation
volume equal to the effective volume of the ST at the activated state, which
represents only a fraction of the complete ST volume. The activation volume is
also found smaller for avalanches, presumably because of accumulated local
damage. This work provides essential information to build reliable mesoscale
models of plasticity.
PMID- 28415290
TI - Backward-stochastic-differential-equation approach to modeling of gene
expression.
AB - In this article, we introduce a backward method to model stochastic gene
expression and protein-level dynamics. The protein amount is regarded as a
diffusion process and is described by a backward stochastic differential equation
(BSDE). Unlike many other SDE techniques proposed in the literature, the BSDE
method is backward in time; that is, instead of initial conditions it requires
the specification of end-point ("final") conditions, in addition to the model
parametrization. To validate our approach we employ Gillespie's stochastic
simulation algorithm (SSA) to generate (forward) benchmark data, according to
predefined gene network models. Numerical simulations show that the BSDE method
is able to correctly infer the protein-level distributions that preceded a known
final condition, obtained originally from the forward SSA. This makes the BSDE
method a powerful systems biology tool for time-reversed simulations, allowing,
for example, the assessment of the biological conditions (e.g., protein
concentrations) that preceded an experimentally measured event of interest (e.g.,
mitosis, apoptosis, etc.).
PMID- 28415292
TI - Current redistribution in resistor networks: Fat-tail statistics in regular and
small-world networks.
AB - The redistribution of electrical currents in resistor networks after single-bond
failures is analyzed in terms of current-redistribution factors that are shown to
depend only on the topology of the network and on the values of the bond
resistances. We investigate the properties of these current-redistribution
factors for regular network topologies (e.g., d-dimensional hypercubic lattices)
as well as for small-world networks. In particular, we find that the statistics
of the current redistribution factors exhibits a fat-tail behavior, which
reflects the long-range nature of the current redistribution as determined by
Kirchhoff's circuit laws.
PMID- 28415291
TI - Experimental demonstration of low laser-plasma instabilities in gas-filled
spherical hohlraums at laser injection angle designed for ignition target.
AB - Octahedral spherical hohlraums with a single laser ring at an injection angle of
55^{?} are attractive concepts for laser indirect drive due to the potential for
achieving the x-ray drive symmetry required for high convergence implosions.
Laser-plasma instabilities, however, are a concern given the long laser
propagation path in such hohlraums. Significant stimulated Raman scattering has
been observed in cylindrical hohlraums with similar laser propagation paths
during the ignition campaign on the National Ignition Facility (NIF). In this
Rapid Communication, experiments demonstrating low levels of laser-driven plasma
instability (LPI) in spherical hohlraums with a laser injection angle of 55^{?}
are reported and compared to that observed with cylindrical hohlraums with
injection angles of 28.5^{?} and 55^{?}, similar to that of the NIF. Significant
LPI is observed with the laser injection of 28.5^{?} in the cylindrical hohlraum
where the propagation path is similar to the 55^{?} injection angle for the
spherical hohlraum. The experiments are performed on the SGIII laser facility
with a total 0.35-MUm incident energy of 93 kJ in a 3 nsec pulse. These
experiments demonstrate the role of hohlraum geometry in LPI and demonstrate the
need for systematic experiments for choosing the optimal configuration for
ignition studies with indirect drive inertial confinement fusion.
PMID- 28415293
TI - Two-component dark-bright solitons in three-dimensional atomic Bose-Einstein
condensates.
AB - In the present work, we revisit two-component Bose-Einstein condensates in their
fully three-dimensional (3D) form. Motivated by earlier studies of dark-bright
solitons in the 1D case, we explore the stability of these structures in their
fully 3D form in two variants. In one the dark soliton is planar and trapping a
planar bright (disk) soliton. In the other case, a dark spherical shell soliton
creates an effective potential in which a bright spherical shell of atoms is
trapped in the second component. We identify these solutions as numerically exact
states (up to a prescribed accuracy) and perform a Bogolyubov-de Gennes
linearization analysis that illustrates that both structures can be dynamically
stable in suitable intervals of sufficiently low chemical potentials. We
corroborate this finding theoretically by analyzing the stability via degenerate
perturbation theory near the linear limit of the system. When the solitary waves
are found to be unstable, we explore their dynamical evolution via direct
numerical simulations which, in turn, reveal wave forms that are more robust.
Finally, using the SO(2) symmetry of the model, we produce multi-dark-bright
planar or shell solitons involved in pairwise oscillatory motion.
PMID- 28415294
TI - Low thermal fluctuations in a system heated out of equilibrium.
AB - We study the mechanical fluctuations of a micrometer sized silicon cantilever
subjected to a strong heat flow, thus having a highly nonuniform local
temperature. In this nonequilibrium steady state, we show that fluctuations are
equivalent to the thermal noise of a cantilever at equilibrium around room
temperature, while its mean local temperature is several hundred degrees higher.
Changing the mechanical dissipation by adding a coating to the cantilever, we
recover the expected rise of fluctuations with the mean temperature. Our work
demonstrates that inhomogeneous dissipation mechanisms can decouple the amplitude
of thermal fluctuations from the average temperature. This property could be
useful to understand out-of-equilibrium fluctuating systems, or to engineer low
noise instruments.
PMID- 28415295
TI - Emergence of Levy walks in systems of interacting individuals.
AB - We propose a model of superdiffusive Levy walk as an emergent nonlinear
phenomenon in systems of interacting individuals. The aim is to provide a
qualitative explanation of recent experiments [G. Ariel et al., Nat. Commun. 6,
8396 (2015)2041-172310.1038/ncomms9396] revealing an intriguing behavior:
swarming bacteria fundamentally change their collective motion from simple
diffusion into a superdiffusive Levy walk dynamics. We introduce microscopic mean
field kinetic equations in which we combine two key ingredients: (1) alignment
interactions between individuals and (2) non-Markovian effects. Our interacting
run-and-tumble model leads to the superdiffusive growth of the mean-squared
displacement and the power-law distribution of run length with infinite variance.
The main result is that the superdiffusive behavior emerges as a cooperative
effect without using the standard assumption of the power-law distribution of run
distances from the inception. At the same time, we find that the collision and
repulsion interactions lead to the density-dependent exponential tempering of
power-law distributions. This qualitatively explains the experimentally observed
transition from superdiffusion to the diffusion of mussels as their density
increases [M. de Jager et al., Proc. R. Soc. B 281, 20132605 (2014)PRLBA40962
845210.1098/rspb.2013.2605].
PMID- 28415296
TI - Nuclear-magnetic-resonance relaxation due to the translational diffusion of fluid
confined to quasi-two-dimensional pores.
AB - Nuclear-magnetic-resonance (NMR) relaxation experimentation is an effective
technique for nondestructively probing the dynamics of proton-bearing fluids in
porous media. The frequency-dependent relaxation rate T_{1}^{-1} can yield a
wealth of information on the fluid dynamics within the pore provided data can be
fit to a suitable spin diffusion model. A spin diffusion model yields the dipolar
correlation function G(t) describing the relative translational motion of pairs
of ^{1}H spins which then can be Fourier transformed to yield T_{1}^{-1}. G(t)
for spins confined to a quasi-two-dimensional (Q2D) pore of thickness h is
determined using theoretical and Monte Carlo techniques. G(t) shows a transition
from three- to two-dimensional motion with the transition time proportional to
h^{2}. T_{1}^{-1} is found to be independent of frequency over the range 0.01-100
MHz provided h?5 nm and increases with decreasing frequency and decreasing h for
pores of thickness h<3 nm. T_{1}^{-1} increases linearly with the bulk water
diffusion correlation time tau_{b} allowing a simple and direct estimate of the
bulk water diffusion coefficient from the high-frequency limit of T_{1}^{-1}
dispersion measurements in systems where the influence of paramagnetic impurities
is negligible. Monte Carlo simulations of hydrated Q2D pores are executed for a
range of surface-to-bulk desorption rates for a thin pore. G(t) is found to
decorrelate when spins move from the surface to the bulk, display three
dimensional properties at intermediate times, and finally show a bulk-mediated
surface diffusion (Levy) mechanism at longer times. The results may be used to
interpret NMR relaxation rates in hydrated porous systems in which the
paramagnetic impurity density is negligible.
PMID- 28415297
TI - Toroidal-droplet instabilities in the presence of charge.
AB - Neutral toroidal droplets can break via the surface-tension-driven Rayleigh
Plateau instability. They can additionally exhibit a shrinking instability, which
is also driven by surface tension, whereby the handle progressively disappears.
We find that charging a toroidal droplet can qualitatively change the behavior
and cause the droplet to expand. We successfully model the transition from
shrinking to expanding, considering the pressure balance across the interface of
the torus. However, despite the change in behavior, charged toroidal droplets end
up breaking into spherical droplets. We quantify how the wavelength of the
fastest unstable mode associated to this breakup depends on the applied voltage
and compare the results with theoretical expectations for charged cylindrical
jets.
PMID- 28415298
TI - Maxwell iteration for the lattice Boltzmann method with diffusive scaling.
AB - In this work, we present an alternative derivation of the Navier-Stokes equations
from Bhatnagar-Gross-Krook models of the lattice Boltzmann method with diffusive
scaling. This derivation is based on the Maxwell iteration and can expose certain
important features of the lattice Boltzmann solutions. Moreover, it will be seen
to be much more straightforward and logically clearer than the existing
approaches including the Chapman-Enskog expansion.
PMID- 28415299
TI - Measurement-induced operation of two-ion quantum heat machines.
AB - We show how one can implement a quantum heat machine by using two interacting
trapped ions, in presence of a thermal bath. The electronic states of the ions
act like a working substance, while the vibrational mode is modelled as the cold
bath. The heat exchange with the cold bath is mimicked by the projective
measurement of the electronic states. We show how such measurement in a suitable
basis can lead to either a quantum heat engine or a refrigerator, which undergoes
a quantum Otto cycle. The local magnetic field is adiabatically changed during
the heat cycle. The performance of the heat machine depends upon the interaction
strength between the ions, the magnetic fields, and the measurement cost. In our
model, the coupling to the hot and the cold baths is never switched off in an
alternative fashion during the heat cycle, unlike other existing proposals of
quantum heat engines. This makes our proposal experimentally realizable using
current tapped-ion technology.
PMID- 28415300
TI - Influence of disorder on generation and probability of extreme events in Salerno
lattices.
AB - Extreme events (EEs) in nonlinear and/or disordered one-dimensional photonic
lattice systems described by the Salerno model with on-site disorder are studied.
The goal is to explain particular properties of these phenomena, essentially
related to localization of light in the presence of nonlinear and/or nonlocal
couplings in the considered systems. Combining statistical and nonlinear
dynamical methods and measures developed in the framework of the theory of
localization phenomena in disordered and nonlinear systems, particularities of
EEs are qualitatively clarified. Findings presented here indicate that the best
environment for EEs' creation are disordered near-integrable Salerno lattices. In
addition, it is been shown that the leading role in the generation and dynamical
properties of EEs in the considered model is played by modulation instability,
i.e., by nonlinearities in the system, although EEs can be induced in linear
lattices with on-site disorder too.
PMID- 28415301
TI - Nonlinear signaling on biological networks: The role of stochasticity and
spectral clustering.
AB - Signal transduction within biological cells is governed by networks of
interacting proteins. Communication between these proteins is mediated by
signaling molecules which bind to receptors and induce stochastic transitions
between different conformational states. Signaling is typically a cooperative
process which requires the occurrence of multiple binding events so that reaction
rates have a nonlinear dependence on the amount of signaling molecule. It is this
nonlinearity that endows biological signaling networks with robust switchlike
properties which are critical to their biological function. In this study we
investigate how the properties of these signaling systems depend on the network
architecture. Our main result is that these nonlinear networks exhibit
bistability where the network activity can switch between states that correspond
to a low and high activity level. We show that this bistable regime emerges at a
critical coupling strength that is determined by the spectral structure of the
network. In particular, the set of nodes that correspond to large components of
the leading eigenvector of the adjacency matrix determines the onset of
bistability. Above this transition the eigenvectors of the adjacency matrix
determine a hierarchy of clusters, defined by its spectral properties, which are
activated sequentially with increasing network activity. We argue further that
the onset of bistability occurs either continuously or discontinuously depending
upon whether the leading eigenvector is localized or delocalized. Finally, we
show that at low network coupling stochastic transitions to the active branch are
also driven by the set of nodes that contribute more strongly to the leading
eigenvector. However, at high coupling, transitions are insensitive to network
structure since the network can be activated by stochastic transitions of a few
nodes. Thus this work identifies important features of biological signaling
networks that may underlie their biological function.
PMID- 28415302
TI - Generalized three-dimensional lattice Boltzmann color-gradient method for
immiscible two-phase pore-scale imbibition and drainage in porous media.
AB - This article presents a three-dimensional numerical framework for the simulation
of fluid-fluid immiscible compounds in complex geometries, based on the multiple
relaxation-time lattice Boltzmann method to model the fluid dynamics and the
color-gradient approach to model multicomponent flow interaction. New lattice
weights for the lattices D3Q15, D3Q19, and D3Q27 that improve the Galilean
invariance of the color-gradient model as well as for modeling the interfacial
tension are derived and provided in the Appendix. The presented method proposes
in particular an approach to model the interaction between the fluid compound and
the solid, and to maintain a precise contact angle between the two-component
interface and the wall. Contrarily to previous approaches proposed in the
literature, this method yields accurate solutions even in complex geometries and
does not suffer from numerical artifacts like nonphysical mass transfer along the
solid wall, which is crucial for modeling imbibition-type problems. The article
also proposes an approach to model inflow and outflow boundaries with the color
gradient method by generalizing the regularized boundary conditions. The
numerical framework is first validated for three-dimensional (3D) stationary
state (Jurin's law) and time-dependent (Washburn's law and capillary waves)
problems. Then, the usefulness of the method for practical problems of pore-scale
flow imbibition and drainage in porous media is demonstrated. Through the
simulation of nonwetting displacement in two-dimensional random porous media
networks, we show that the model properly reproduces three main invasion regimes
(stable displacement, capillary fingering, and viscous fingering) as well as the
saturating zone transition between these regimes. Finally, the ability to
simulate immiscible two-component flow imbibition and drainage is validated, with
excellent results, by numerical simulations in a Berea sandstone, a frequently
used benchmark case used in this field, using a complex geometry that originates
from a 3D scan of a porous sandstone. The methods presented in this article were
implemented in the open-source PALABOS library, a general C++ matrix-based
library well adapted for massive fluid flow parallel computation.
PMID- 28415303
TI - Generic patterns in the evolution of urban water networks: Evidence from a large
Asian city.
AB - We examine high-resolution urban infrastructure data using every pipe for the
water distribution network (WDN) and sanitary sewer network (SSN) in a large
Asian city (~4 million residents) to explore the structure as well as the spatial
and temporal evolution of these infrastructure networks. Network data were
spatially disaggregated into multiple subnets to examine intracity topological
differences for functional zones of the WDN and SSN, and time-stamped SSN data
were examined to understand network evolution over several decades as the city
expanded. Graphs were generated using a dual-mapping technique (Hierarchical
Intersection Continuity Negotiation), which emphasizes the functional attributes
of these networks. Network graphs for WDNs and SSNs are characterized by several
network topological metrics, and a double Pareto (power-law) model approximates
the node-degree distributions of both water infrastructure networks (WDN and
SSN), across spatial and hierarchical scales relevant to urban settings, and
throughout their temporal evolution over several decades. These results indicate
that generic mechanisms govern the networks' evolution, similar to those of scale
free networks found in nature. Deviations from the general topological patterns
are indicative of (1) incomplete establishment of network hierarchies and
functional network evolution, (2) capacity for growth (expansion) or
densification (e.g., in-fill), and (3) likely network vulnerabilities. We discuss
the implications of our findings for the (re-)design of urban infrastructure
networks to enhance their resilience to external and internal threats.
PMID- 28415304
TI - Measurement of the equation of state of solid-density copper heated with laser
accelerated protons.
AB - We present equation of state (EOS) measurements of solid-density copper heated to
5-10 eV. A copper sample was heated isochorically by hydrogen ions accelerated
from an adjacent foil by a high intensity pulsed laser, and probed optically. The
measured temperature and expansion are compared against simulations using the
most up-to-date wide range EOS tables available.
PMID- 28415305
TI - Upper bound for the average entropy production based on stochastic entropy
extrema.
AB - The second law of thermodynamics, which asserts the non-negativity of the average
total entropy production of a combined system and its environment, is a direct
consequence of applying Jensen's inequality to a fluctuation relation. It is also
possible, through this inequality, to determine an upper bound of the average
total entropy production based on the entropies along the most extreme stochastic
trajectories. In this work, we construct an upper bound inequality of the average
of a convex function over a domain whose average is known. When applied to the
various fluctuation relations, the upper bounds of the average total entropy
production are established. Finally, by employing the result of Neri, Roldan, and
Julicher [Phys. Rev. X 7, 011019 (2017)]10.1103/PhysRevX.7.011019, we are able to
show that the average total entropy production is bounded only by the total
entropy production supremum, and vice versa, for a general nonequilibrium
stationary system.
PMID- 28415306
TI - Gaussian white noise as a resource for work extraction.
AB - We show that uncorrelated Gaussian noise can drive a system out of equilibrium
and can serve as a resource from which work can be extracted. We consider an
overdamped particle in a periodic potential with an internal degree of freedom
and a state-dependent friction, coupled to an equilibrium bath. Applying
additional Gaussian white noise drives the system into a nonequilibrium steady
state and causes a finite current if the potential is spatially asymmetric. The
model thus operates as a Brownian ratchet, whose current we calculate explicitly
in three complementary limits. Since the particle current is driven solely by
additive Gaussian white noise, this shows that the latter can potentially perform
work against an external load. By comparing the extracted power to the energy
injection due to the noise, we discuss the efficiency of such a ratchet.
PMID- 28415307
TI - Decoding heat capacity features from the energy landscape.
AB - A general scheme is derived to connect transitions in configuration space with
features in the heat capacity. A formulation in terms of occupation probabilities
for local minima that define the potential energy landscape provides a
quantitative description of how contributions arise from competition between
different states. The theory does not rely on a structural interpretation for the
local minima, so it is equally applicable to molecular energy landscapes and the
landscapes defined by abstract functions. Applications are presented for low
temperature solid-solid transitions in atomic clusters, which involve just a few
local minima with different morphologies, and for cluster melting, which is
driven by the landscape entropy associated with the more numerous high-energy
minima. Analyzing these features in terms of the balance between states with
increasing and decreasing occupation probabilities provides a direct
interpretation of the underlying transitions. This approach enables us to
identify a qualitatively different transition that is caused by a single local
minimum associated with an exceptionally large catchment volume in configuration
space for a machine learning landscape.
PMID- 28415308
TI - Thermal transport in the Fermi-Pasta-Ulam model with long-range interactions.
AB - We study the thermal transport properties of the one-dimensional Fermi-Pasta-Ulam
model (beta type) with long-range interactions. The strength of the long-range
interaction decreases with the (shortest) distance between the lattice sites as
distance^{-delta}, where delta>=0. Two Langevin heat baths at unequal
temperatures are connected to the ends of the one-dimensional lattice via short
range harmonic interactions that drive the system away from thermal equilibrium.
In the nonequilibrium steady state the heat current, thermal conductivity, and
temperature profiles are computed by solving the equations of motion numerically.
It is found that the conductivity kappa has an interesting nonmonotonic
dependence with delta with a maximum at delta=2.0 for this model. Moreover, at
delta=2.0,kappa diverges almost linearly with system size N and the temperature
profile has a negligible slope, as one expects in ballistic transport for an
integrable system. We demonstrate that the nonmonotonic behavior of the
conductivity and the nearly ballistic thermal transport at delta=2.0 obtained
under nonequilibrium conditions can be explained consistently by studying the
variation of largest Lyapunov exponent lambda_{max} with delta, and excess energy
diffusion in the equilibrium microcanonical system.
PMID- 28415310
TI - Structure-properties relation for random networks of fibers with noncircular
cross section.
AB - The mechanical behavior of three-dimensional cross-linked random fiber networks
composed from fibers of noncircular cross section characterized by two principal
moments of inertia is studied in this work. Such fibers store energy in the axial
deformation mode and two bending modes of unequal stiffness. We show that the
torsional stiffness of fibers becomes important as it determines the relative
contribution of the two bending modes to the overall deformation. The scaling of
the small strain modulus with the network parameters is established. The large
strain deformation of these structures is less sensitive to the shape of the
cross section.
PMID- 28415309
TI - Laplacian networks: Growth, local symmetry, and shape optimization.
AB - Inspired by river networks and other structures formed by Laplacian growth, we
use the Loewner equation to investigate the growth of a network of thin fingers
in a diffusion field. We first review previous contributions to illustrate how
this formalism reduces the network's expansion to three rules, which respectively
govern the velocity, the direction, and the nucleation of its growing branches.
This framework allows us to establish the mathematical equivalence between three
formulations of the direction rule, namely geodesic growth, growth that maintains
local symmetry, and growth that maximizes flux into tips for a given amount of
growth. Surprisingly, we find that this growth rule may result in a network
different from the static configuration that optimizes flux into tips.
PMID- 28415311
TI - Understanding quantum work in a quantum many-body system.
AB - Based on previous studies in a single-particle system in both the integrable
[Jarzynski, Quan, and Rahav, Phys. Rev. X 5, 031038 (2015)2160
330810.1103/PhysRevX.5.031038] and the chaotic systems [Zhu, Gong, Wu, and Quan,
Phys. Rev. E 93, 062108 (2016)1539-375510.1103/PhysRevE.93.062108], we study the
the correspondence principle between quantum and classical work distributions in
a quantum many-body system. Even though the interaction and the
indistinguishability of identical particles increase the complexity of the
system, we find that for a quantum many-body system the quantum work distribution
still converges to its classical counterpart in the semiclassical limit. Our
results imply that there exists a correspondence principle between quantum and
classical work distributions in an interacting quantum many-body system,
especially in the large particle number limit, and further justify the definition
of quantum work via two-point energy measurements in quantum many-body systems.
PMID- 28415312
TI - Nonlinear effects in the bounded dust-vortex flow in plasma.
AB - The vortex structures in a cloud of electrically suspended dust in a streaming
plasma constitutes a driven system with a rich nonlinear flow regime.
Experimentally recovered toroidal formations of this system have motivated study
of its volumetrically driven-dissipative vortex flow dynamics using two
dimensional hydrodynamics in the incompressible Navier-Stokes regime. Nonlinear
equilibrium solutions are obtained for this system where a nonuniformly driven
two-dimensional dust flow exhibits distinct regions of localized accelerations
and strong friction caused by stationary fluids at the confining boundaries
resisting the dust flow. In agreement with observations in experiments, it is
demonstrated that the nonlinear effects appear in the limit of small viscosity,
where the primary vortices form scaling with the most dominant spatial scales of
the domain topology and develop separated virtual boundaries along their
periphery. This separation is triggered beyond a critical dust viscosity that
signifies a structural bifurcation. Emergence of uniform vorticity core and
secondary vortices with a newer level of identical dynamics highlights the
applicability of the studied dynamics to gigantic vortex flows, such as the
Jovian great red spot, to microscopic biophysical intracellular activity.
PMID- 28415313
TI - Characterization of phase transitions in a model ecosystem of sessile species.
AB - We consider a model ecosystem of sessile species competing for space. In
particular, we consider the system introduced by Mathiesen et al. [J. Mathiesen,
N. Mitarai, K. Sneppen, and A. Trusina, Phys. Rev. Lett. 107, 188101
(2011)PRLTAO0031-900710.1103/PhysRevLett.107.188101] where species compete
according to a fixed interaction network with links determined by a Bernoulli
process. In the limit of a small introduction rate of new species, the model
exhibits a discontinuous transition from a high-diversity state to a low
diversity state as the interaction probability between species, gamma, is
increased from zero. Here we explore the effects of finite introduction rates and
system size on the phase transition by utilizing efficient parallel computing. We
find that the low state appears for gamma>gamma_{c}. As gamma is increased
further, the high state approaches the low state, suggesting the possibility that
the two states merge at a high gamma. We find that the fraction of time spent in
the high state becomes longer with higher introduction rates, but the
availability of the two states is rather insensitive to the value of the
introduction rate. Furthermore, we establish a relation between the introduction
rate and the system size, which preserves the probability for the system to
remain in the high-diversity state.
PMID- 28415314
TI - Cell-alignment patterns in the collective migration of cells with polarized
adhesion.
AB - Dictyostelium discoideum (Dd) utilizes inhomogeneities in the distribution of
cell-cell adhesion molecules on cell membranes for collective cell migration. A
simple example of an inhomogeneity is a front-side (leading-edge) polarization in
the distribution at the early streaming stage. Experiments have shown that the
polarized cell-cell adhesion induces side-by-side contact between cells [Beug et
al., Nature (London) 274, 445 (1978)NATUAS0028-083610.1038/274445a0]. This result
is counterintuitive, as one would expect cells to align front to front in contact
with each other on the basis of front-side polarization. In this work, we
theoretically examine whether front-side polarization induces side-by-side
contact in collective cell migration. We construct a model for expressing cells
with this polarization based on the two-dimensional cellular Potts model. By a
numerical simulation with this model, we find cell-cell alignment wherein cells
form lateral arrays with side-by-side contacts as observed in the experiments.
PMID- 28415315
TI - Rectification and one-way street for the energy current in boundary-driven
asymmetric quantum spin chains.
AB - Motivated by the demand for efficient quantum devices to engineer energy
transport, we analyze some inhomogeneous quantum spin systems, including XXZ
chains, with magnetization baths at the ends. With a goal of finding general
properties, we study the effects of suitable transformations on the boundary
driven Lindblad master equation associated with the dynamics of the systems. For
asymmetric models with target polarization at the edges or twisted XY boundary
gradients, we show the properties of the steady state, which establish the
features of the energy current irrespective of the system size and the regime of
transport. We show the ubiquitous occurrence of energy rectification and, more
interestingly, of an unusual phenomenon: in the absence of an external magnetic
field, there is a one-way street for the energy current, i.e., the direction of
the energy current does not change as we invert the magnetization baths at the
boundaries. Given the extensiveness of the procedures, which essentially involve
the properties of the Lindblad master equation, our results certainly follow for
other interactions and other boundary conditions. Moreover, our results indicate
graded spin chains as genuine quantum rectifiers.
PMID- 28415316
TI - Spheroidal harmonic expansions for the solution of Laplace's equation for a point
source near a sphere.
AB - We propose a powerful approach to solve Laplace's equation for point sources near
a spherical object. The central new idea is to use prolate spheroidal solid
harmonics, which are separable solutions of Laplace's equation in spheroidal
coordinates, instead of the more natural spherical solid harmonics. Using
electrostatics as an example, we motivate this choice and show that the resulting
series expansions converge much faster. This improvement is discussed in terms of
the singularity of the solution and its analytic continuation. The benefits of
this approach are further illustrated for a specific example: the calculation of
modified decay rates of light emitters close to nanostructures in the quasistatic
approximation. We expect the general approach to be applicable with similar
benefits to the solution of Laplace's equation for other geometries and to other
equations of mathematical physics.
PMID- 28415317
TI - Reorientations of the large-scale flow in turbulent convection in a cube.
AB - Large-eddy simulations of turbulent Rayleigh-Benard convection were conducted for
a fluid of Prandtl number Pr=0.7 confined in a cube, for Rayleigh numbers of
10^{6} and 10^{8}. The model solves the unsteady Navier-Stokes equations under
the Boussinesq approximation, using a dynamic Smagorinsky model with a Lagrangian
averaging technique for the subgrid terms. Under fully developed conditions the
flow topology is characterized by a large-scale circulation (LSC) developing in a
plane containing one of the diagonals of the cell, while two counter-rotating
vortices consequently develop in the other diagonal plane, resulting in a strong
inflow at the horizontal midplane. This flow structure is not static, with the
LSC undergoing nonperiodic reorientations, or switching, between the two diagonal
planes; hence, we supplement the observations of the three-dimensional time
averaged flow structures with single point measurements (time series) to shed
light on the dynamics of the reorientations. For all observations, this switching
results from a lateral rotation of the LSC in which some finite time spent in a
transient state where the large-scale circulation is parallel to one set of side
walls; there are, importantly, no observations consistent with so-called
cessations of the LSC, in which it decays and then reforms in another plane
without such a rotation. The average switching rate for the LSC is in excellent
agreement with the results of Bai et al. [K. Bai, D. Ji, and E. Brown, Phys. Rev.
E 93, 023117 (2016)PLEEE81539-375510.1103/PhysRevE.93.023117].
PMID- 28415318
TI - Effects of spatial and temporal noise on a cubic-autocatalytic reaction-diffusion
model.
AB - We characterize the influence that external noise, with both spatial and temporal
correlations, has on the scale dependence of the reaction parameters of a cubic
autocatalytic reaction diffusion (CARD) system. Interpreting the CARD model as a
primitive reaction scheme for a living system, the results indicate that power
law correlations in environmental fluctuations can either decrease or increase
the rates of nutrient decay and the rate of autocatalysis (replication) on small
spatial and temporal scales.
PMID- 28415319
TI - Footprint geometry and sessile drop resonance.
AB - In this work, we examine experimentally the resonance of a sessile drop with a
square footprint (square drop) on a flat plate. Two families of modal behaviors
are reported. One family is identified with the modes of sessile drops with
circular footprints (circular drop), denoted as "spherical modes." The other
family is associated with Faraday waves on a square liquid bath (square Faraday
waves), denoted as "grid modes." The two families are distinguished based on
their dispersion behaviors. By comparing the occurrence of the modes, we
recognize spherical modes as the characteristic of sessile drops, and grid modes
as the constrained response. Within a broader context, we further discuss the
resonance modes of circular sessile drops and free spherical drops, and we
recognize various modal behaviors as surface waves under different extents of
constraint. From these, we conclude that sessile drops resonate according to how
wave-number selection by footprint geometry and capillarity compete. For square
drops, a dominant effect of footprint constraint leads to grid modes; otherwise,
the drops exhibit spherical modes, the characteristic of sessile drops on flat
plates.
PMID- 28415320
TI - Background scalar-level anisotropy caused by low-wave-number truncation in
turbulent flows.
AB - We rigorously show that the truncation at low wave numbers always leads to
background scalar-level anisotropy at large scales. Neither the resolution nor
the spectral low-pass filter is dominant for this anisotropy, while the shape of
the energy spectrum at low wave numbers is an important influence factor.
Quantitative results are shown to provide references to the statistics in future
postprocessing studies. Also, a simplified analytical model is introduced to
explain the single-mode effects for this anisotropy.
PMID- 28415321
TI - Sedimentation equilibrium of magnetic nanoparticles with strong dipole-dipole
interactions.
AB - Langevin dynamics simulation is used to study the suspension of interacting
magnetic nanoparticles (dipolar spheres) in a zero applied magnetic field and in
the presence of a gravitational (centrifugal) field. A particular emphasis is
placed on the equilibrium vertical distribution of particles in the infinite
horizontal slab. An increase in the dipolar coupling constant lambda (the ratio
of dipole-dipole interaction energy to thermal energy) from zero to seven units
causes an increase in the particle segregation coefficient by several orders of
magnitude. The effect of anisotropic dipole-dipole interactions on the
concentration profile of particles is the same as that of the isotropic van der
Waals attraction modeled by the Lennard-Jones potential. In both cases, the area
with a high-density gradient separating the area with high and low particle
concentration is formed on the profiles. Qualitative difference between two
potentials manifests itself only in the fact that in the absence of a
gravitational field the dipole-dipole interactions do not lead to the "gas
liquid" phase transition: no separation of the system into weakly and highly
concentrated phases is observed. At high particle concentration and at large
values of lambda, the orientational ordering of magnetic dipoles takes place in
the system. Magnetic structure of the system strongly depends on the imposed
boundary conditions. Spontaneous magnetization occurs in the infinite horizontal
slab (i.e., in the rectangular cell with two-dimensional periodic boundary
conditions). Replacement of the infinite slab by the finite-size hard-wall
vertical cylinder leads to the formation of azimuthal (vortex-like) order. The
critical values of the coupling constant corresponding to the transition into an
ordered state are very close for two geometries.
PMID- 28415322
TI - Thermal rectification in mass-graded next-nearest-neighbor Fermi-Pasta-Ulam
lattices.
AB - We study the thermal rectification efficiency, i.e., quantification of asymmetric
heat flow, of a one-dimensional mass-graded anharmonic oscillator Fermi-Pasta
Ulam lattice both with nearest-neighbor (NN) and next-nearest-neighbor (NNN)
interactions. The system presents a maximum rectification efficiency for a very
precise value of the parameter that controls the coupling strength of the NNN
interactions, which also optimizes the rectification figure when its dependence
on mass asymmetry and temperature differences is considered. The origin of the
enhanced rectification is the asymmetric local heat flow response as the heat
reservoirs are swapped when a finely tuned NNN contribution is taken into
account. A simple theoretical analysis gives an estimate of the optimal NNN
coupling in excellent agreement with our simulation results.
PMID- 28415324
TI - Scale dependence of multiplier distributions for particle concentration,
enstrophy, and dissipation in the inertial range of homogeneous turbulence.
AB - Turbulent flows preferentially concentrate inertial particles depending on their
stopping time or Stokes number, which can lead to significant spatial variations
in the particle concentration. Cascade models are one way to describe this
process in statistical terms. Here, we use a direct numerical simulation (DNS)
dataset of homogeneous, isotropic turbulence to determine probability
distribution functions (PDFs) for cascade multipliers, which determine the ratio
by which a property is partitioned into subvolumes as an eddy is envisioned to
decay into smaller eddies. We present a technique for correcting effects of small
particle numbers in the statistics. We determine multiplier PDFs for particle
number, flow dissipation, and enstrophy, all of which are shown to be scale
dependent. However, the particle multiplier PDFs collapse when scaled with an
appropriately defined local Stokes number. As anticipated from earlier works,
dissipation and enstrophy multiplier PDFs reach an asymptote for sufficiently
small spatial scales. From the DNS measurements, we derive a cascade model that
is used it to make predictions for the radial distribution function (RDF) for
arbitrarily high Reynolds numbers, Re, finding good agreement with the
asymptotic, infinite Re inertial range theory of Zaichik and Alipchenkov [New J.
Phys. 11, 103018 (2009)NJOPFM1367-263010.1088/1367-2630/11/10/103018]. We discuss
implications of these results for the statistical modeling of the turbulent
clustering process in the inertial range for high Reynolds numbers inaccessible
to numerical simulations.
PMID- 28415323
TI - Variable species densities are induced by volume exclusion interactions upon
domain growth.
AB - In this work we study the effect of domain growth on spatial correlations in
agent populations containing multiple species. This is important as heterogenous
cell populations are ubiquitous during the embryonic development of many species.
We have previously shown that the long-term behavior of an agent population
depends on the way in which domain growth is implemented. We extend this work to
show that, depending on the way in which domain growth is implemented, different
species dominate in multispecies simulations. Continuum approximations of the
lattice-based model that ignore spatial correlations cannot capture this
behavior, while those that explicitly account for spatial correlations can. The
results presented here show that the precise mechanism of domain growth can
determine the long-term behavior of multispecies populations and, in certain
circumstances, establish spatially varying species densities.
PMID- 28415325
TI - Modulation of unpolarized light in planar-aligned subwavelength-pitch deformed
helix ferroelectric liquid crystals.
AB - We study the electro-optic properties of subwavelength-pitch deformed-helix
ferroelectric liquid crystals (DHFLC) illuminated with unpolarized light. In the
experimental setup based on the Mach-Zehnder interferometer, it was observed that
the reference and the sample beams being both unpolarized produce the
interference pattern which is insensitive to rotation of in-plane optical axes of
the DHFLC cell. We find that the field-induced shift of the interference fringes
can be described in terms of the electrically dependent Pancharatnam relative
phase determined by the averaged phase shift, whereas the visibility of the
fringes is solely dictated by the phase retardation.
PMID- 28415326
TI - Numerical study of one-dimensional compression of granular materials. II. Elastic
moduli, stresses, and microstructure.
AB - The elastic moduli of a transversely isotropic model granular material, made of
slightly polydisperse elastic-frictional spherical beads, in equilibrium along a
one-dimensional (oedometric) compression path, as described in the companion
paper [M. H. Khalili et al., Phys. Rev. E 95, 032907
(2017)]10.1103/PhysRevE.95.032907, are investigated by numerical simulations. The
relations of the five independent moduli to stresses, density, coordination
number, fabric and force anisotropies are studied for different internal material
states along the oedometric loading path. It is observed that elastic moduli, as
in isotropic packs, are primarily determined by the coordination number, with
anomalously small shear moduli in poorly coordinated systems, whatever their
density. Such states also exhibit faster increasing moduli in compression, and
larger off-diagonal moduli and Poisson ratios. Anisotropy affects the
longitudinal moduli C_{11} in the axial direction and C_{22} in the transverse
directions, and the shear modulus in the transverse plane C_{44}, more than the
shear modulus in a plane containing the axial direction C_{55}. The results are
compared to available experiments on anisotropic bead packs, revealing, despite
likely differences in internal states, a very similar range of stiffness level
(linked to coordination), and semiquantitative agreement as regards the influence
of anisotropy. Effective medium theory (the Voigt approach) provides quite
inaccurate predictions of the moduli. It also significantly underestimates ratios
C_{11}/C_{22} (varying between 1 and 2.2) and C_{55}/C_{44} (varying from 1 to
1.6), which characterize elastic anisotropy, except in relatively weakly
anisotropic states. The bulk modulus for isotropic compression and the compliance
corresponding to stress increments proportional to the previous stress values are
the only elastic coefficients to be correctly estimated by available predictive
relations. We discuss the influences of fabric and force anisotropies onto
elastic anisotropy, showing in particular that the former dominates in sample
series that are directly assembled in anisotropic configurations and keep a
roughly constant lateral to axial stress ratio under compression.
PMID- 28415327
TI - Facets on the convex hull of d-dimensional Brownian and Levy motion.
AB - For stationary, homogeneous Markov processes (viz., Levy processes, including
Brownian motion) in dimension d>=3, we establish an exact formula for the average
number of (d-1)-dimensional facets that can be defined by d points on the
process's path. This formula defines a universality class in that it is
independent of the increments' distribution, and it admits a closed form when
d=3, a case which is of particular interest for applications in biophysics,
chemistry, and polymer science. We also show that the asymptotical average number
of facets behaves as ~2[ln(T/Deltat)]^{d-1}, where T is the total
duration of the motion and Deltat is the minimum time lapse separating points
that define a facet.
PMID- 28415328
TI - Asymmetric transmission of sound wave in cavitating liquids.
AB - Two modes of the asymmetric sound transmission are observed experimentally in a
one-dimensional system composed of coupled two layers of liquids. Their
cavitation thresholds are different from each other. When the sound wave
propagates from the high-threshold liquid to the low-threshold liquid, the two
liquids can avoid the cavitation for a medium driving pressure. When it
propagates from the low-threshold liquid to the high-threshold liquid, however,
the low-threshold liquid can be cavitated by the same driving pressure, though
the high-threshold liquid remains uncavitated. Therefore, there is a sound
transmission asymmetry, or sound rectification in this double-layer liquid.
Furthermore, when the system is driven by a high pressure, cavitation can take
place in both high- and low-threshold liquids in the sound transmission from the
high-threshold liquid to the low-threshold liquid, but only the low-threshold
liquid can be cavitated in the opposite transmission. This mechanism gives an
asymmetry with reversed rectifying direction. The efficiency of rectification is
related to the driving sound pressure and the cavitation thresholds of the two
liquids based on experimental results. Finally, the experimental observations are
reproduced by the numerical simulation based on the modified two-phase fluid
mechanics.
PMID- 28415329
TI - Kardar-Parisi-Zhang equation with short-range correlated noise: Emergent
symmetries and nonuniversal observables.
AB - We investigate the stationary-state fluctuations of a growing one-dimensional
interface described by the Kardar-Parisi-Zhang (KPZ) dynamics with a noise
featuring smooth spatial correlations of characteristic range xi. We employ
nonperturbative functional renormalization group methods to resolve the
properties of the system at all scales. We show that the physics of the standard
(uncorrelated) KPZ equation emerges on large scales independently of xi.
Moreover, the renormalization group flow is followed from the initial condition
to the fixed point, that is, from the microscopic dynamics to the large-distance
properties. This provides access to the small-scale features (and their
dependence on the details of the noise correlations) as well as to the universal
large-scale physics. In particular, we compute the kinetic energy spectrum of the
stationary state as well as its nonuniversal amplitude. The latter is
experimentally accessible by measurements at large scales and retains a signature
of the microscopic noise correlations. Our results are compared to previous
analytical and numerical results from independent approaches. They are in
agreement with direct numerical simulations for the kinetic energy spectrum as
well as with the prediction, obtained with the replica trick by Gaussian
variational method, of a crossover in xi of the nonuniversal amplitude of this
spectrum.
PMID- 28415330
TI - Performance of a quantum heat engine at strong reservoir coupling.
AB - We study a quantum heat engine at strong coupling between the system and the
thermal reservoirs. Exploiting a collective coordinate mapping, we incorporate
system-reservoir correlations into a consistent thermodynamic analysis, thus
circumventing the usual restriction to weak coupling and vanishing correlations.
We apply our formalism to the example of a quantum Otto cycle, demonstrating that
the performance of the engine is diminished in the strong coupling regime with
respect to its weakly coupled counterpart, producing a reduced net work output
and operating at a lower energy conversion efficiency. We identify costs imposed
by sudden decoupling of the system and reservoirs around the cycle as being
primarily responsible for the diminished performance, and we define an
alternative operational procedure which can partially recover the work output and
efficiency. More generally, the collective coordinate mapping holds considerable
promise for wider studies of thermodynamic systems beyond weak reservoir
coupling.
PMID- 28415331
TI - Transition radiation at the boundary of a chiral isotropic medium.
AB - This study analyzes the radiation produced by a point charge intersecting the
interface between a vacuum and a chiral isotropic medium. We deduce analytical
expressions for the Fourier components of an electromagnetic field in both vacuum
and medium for arbitrary charge velocity. The main focus is on investigating the
far field in a vacuum. The distinguishing feature of the interface with a chiral
isotropic medium is that the field in the vacuum area contains both
copolarization (coinciding with the polarization of the self-field of a charge)
and cross-polarization (orthogonal to the polarization of the self-field). Using
a saddle-point approach, we obtain asymptotic representations for the field
components in the far-field zone for typical frequency ranges of the Condon model
of the chiral medium. We note that a so-called lateral wave is generated in a
vacuum for certain parameters. The main contribution to the radiation at large
distances is presented by two (co- and cross-) spherical waves of transition
radiation. These waves are coherent and result in a total spherical wave with
elliptical polarization, with the polarization coefficient being determined by
the chirality of the medium. We present typical radiation patterns and ellipses
of polarization.
PMID- 28415332
TI - Numerical simulations of Ising spin glasses with free boundary conditions: The
role of droplet excitations and domain walls.
AB - The relative importance of the contributions of droplet excitations and domain
walls on the ordering of short-range Edwards-Anderson spin glasses in three and
four dimensions is studied. We compare the spin overlap distribution functions of
periodic and free boundary conditions using population annealing Monte Carlo. For
system sizes up to about 1000 spins, spin glasses show nontrivial spin overlap
distributions. Periodic boundary conditions may trap diffusive domain walls which
can contribute to small spin overlaps, and the other contribution is the
existence of low-energy droplet excitations within the system. We use free
boundary conditions to minimize domain-wall effects, and show that low-energy
droplet excitations are the major contribution to small overlaps in numerical
simulations. Free boundary conditions has stronger finite-size effects, and is
likely to have the same thermodynamic limit with periodic boundary conditions.
PMID- 28415333
TI - Melting of a nonequilibrium vortex crystal in a fluid film with polymers: Elastic
versus fluid turbulence.
AB - We perform a direct numerical simulation of the forced, incompressible two
dimensional Navier-Stokes equation coupled with the FENE-P equations for the
polymer-conformation tensor. The forcing is such that, without polymers and at
low Reynolds numbers Re, the film attains a steady state that is a square lattice
of vortices and antivortices. We find that, as we increase the Weissenberg number
Wi, a sequence of nonequilibrium phase transitions transforms this lattice, first
to spatially distorted, but temporally steady, crystals and then to a sequence of
crystals that oscillate in time, periodically, at low Wi, and quasiperiodically,
for slightly larger Wi. Finally, the system becomes disordered and displays
spatiotemporal chaos and elastic turbulence. We then obtain the nonequilibrium
phase diagram for this system, in the Wi-Omega plane, where Omega?Re, and show
that (a) the boundary between the crystalline and turbulent phases has a
complicated, fractal-type character and (b) the Okubo-Weiss parameter Lambda
provides us with a natural measure for characterizing the phases and transitions
in this diagram.
PMID- 28415334
TI - Quantum Jarzynski equality of measurement-based work extraction.
AB - Many studies of quantum-size heat engines assume that the dynamics of an internal
system is unitary and that the extracted work is equal to the energy loss of the
internal system. Both assumptions, however, should be under scrutiny. In the
present paper, we analyze quantum-scale heat engines, employing the measurement
based formulation of the work extraction recently introduced by Hayashi and
Tajima [M. Hayashi and H. Tajima, arXiv:1504.06150]. We first demonstrate the
inappropriateness of the unitary time evolution of the internal system (namely,
the first assumption above) using a simple two-level system; we show that the
variance of the energy transferred to an external system diverges when the
dynamics of the internal system is approximated to a unitary time evolution.
Second, we derive the quantum Jarzynski equality based on the formulation of
Hayashi and Tajima as a relation for the work measured by an external macroscopic
apparatus. The right-hand side of the equality reduces to unity for "natural"
cyclic processes but fluctuates wildly for noncyclic ones, exceeding unity often.
This fluctuation should be detectable in experiments and provide evidence for the
present formulation.
PMID- 28415335
TI - Effectively explore metastable states of proteins by adaptive nonequilibrium
driving simulations.
AB - Nonequilibrium drivings applied in molecular dynamics (MD) simulations can
efficiently extend the visiting range of protein conformations, but might compel
systems to go far away from equilibrium and thus mainly explore irrelevant
conformations. Here we propose a general method, called adaptive nonequilibrium
simulation (ANES), to automatically adjust the external driving on the fly, based
on the feedback of the short-time average response of system. Thus, the ANES
approximately keeps the local equilibrium but efficiently accelerates the global
motion. We illustrate the capability of the ANES in highly efficiently exploring
metastable conformations in the deca-alanine peptide and find that the 0.2-MUs
ANES approximately captures the important states and folding and unfolding
pathways in the HP35 solution by comparing with the result of the recent 398-MUs
equilibrium MD simulation on Anton [S. Piana et al., Proc. Natl. Acad. Sci. USA
109, 17845 (2012)PNASA60027-842410.1073/pnas.1201811109].
PMID- 28415336
TI - Arrays of two-state stochastic oscillators: Roles of tail and range of
interactions.
AB - We study the role of the tail and the range of interaction in a spatially
structured population of two-state on-off units governed by Markovian transition
rates. The coupling among the oscillators is evidenced by the dependence of the
transition rates of each unit on the states of the units to which it is coupled.
Tuning the tail or range of the interactions, we observe a transition from an
ordered global state (long-range interactions) to a disordered one (short-range
interactions). Depending on the interaction kernel, the transition may be smooth
(second order) or abrupt (first order). We analyze the transient, which may
present different routes to the steady state with vastly different time scales.
PMID- 28415337
TI - Mean-squared-displacement statistical test for fractional Brownian motion.
AB - Anomalous diffusion in crowded fluids, e.g., in cytoplasm of living cells, is a
frequent phenomenon. A common tool by which the anomalous diffusion of a single
particle can be classified is the time-averaged mean square displacement (TAMSD).
A classical mechanism leading to the anomalous diffusion is the fractional
Brownian motion (FBM). A validation of such process for single-particle tracking
data is of great interest for experimentalists. In this paper we propose a
rigorous statistical test for FBM based on TAMSD. To this end we analyze the
distribution of the TAMSD statistic, which is given by the generalized chi
squared distribution. Next, we study the power of the test by means of Monte
Carlo simulations. We show that the test is very sensitive for changes of the
Hurst parameter. Moreover, it can easily distinguish between two models of
subdiffusion: FBM and continuous-time random walk.
PMID- 28415338
TI - Elastic anisotropy effects on the electrical responses of a thin sample of
nematic liquid crystal.
AB - The electrical responses of a nematic liquid crystal cell are investigated by
means of the elastic continuum theory. The nematic medium is considered as a
parallel circuit of a resistance and a capacitance and the electric current
profile across the sample is determined as a function of the elastic constants.
In the reorientation process of the nematic director, the resistance and
capacitance of the sample are determined by taking into account the elastic
anisotropy. A nonmonotonic profile for the current is observed in which a minimum
value of the current may be used to estimate the elastic constants values. This
scenario suggests a theoretical method to determine the values of the bulk
elastic constants in a single planar aligned cell just by changing the direction
of applied electrical field and measuring the resulting electrical current.
PMID- 28415339
TI - Fast forward to the classical adiabatic invariant.
AB - We show how the classical action, an adiabatic invariant, can be preserved under
nonadiabatic conditions. Specifically, for a time-dependent Hamiltonian
H=p^{2}/2m+U(q,t) in one degree of freedom, and for an arbitrary choice of action
I_{0}, we construct a so-called fast-forward potential energy function
V_{FF}(q,t) that, when added to H, guides all trajectories with initial action
I_{0} to end with the same value of action. We use this result to construct a
local dynamical invariant J(q,p,t) whose value remains constant along these
trajectories. We illustrate our results with numerical simulations. Finally, we
sketch how our classical results may be used to design approximate quantum
shortcuts to adiabaticity.
PMID- 28415340
TI - Development of kinks in car-following models.
AB - Many car-following models of traffic flow admit the possibility of absolute
stability, a situation in which uniform traffic flow at any spacing is linearly
stable. Near the threshold of absolute stability, these models can often be
reduced to a modified Korteweg-deVries (mKdV) equation plus small corrections.
The hyperbolic-tangent "kink" solutions of the mKdV equation are usually of
particular interest, as they represent transition zones between regions of
different traffic spacings. Solvability analysis is believed to show that only a
single member of the one-parameter family of kink solutions is preserved by the
correction terms, and this is interpreted as a kind of selection. We show,
however, that the usual solvability calculation rests on an unstated, unjustified
assumption, and that without this assumption it merely gives a first-order
correction to the relation between the traffic spacings far behind and far ahead
of the kink, rather than any kind of "selection" criterion for the family of kink
solutions. On the other hand, we display a two-parameter family of traveling wave
solutions of the mKdV equation, which describe regions of one traffic spacing
embedded in traffic of a different spacing; this family includes the kink
solutions as a limiting case. We carry out a multiple-time-scales calculation and
find conditions under which the inclusions decay, conditions that lead to a
selected inclusion, and conditions for which the inclusion evolves into a pair of
kinks.
PMID- 28415341
TI - Influence of orientation on the evolution of small perturbations in compressible
shear layers with inflection points.
AB - We investigate the influence of orientation on the evolution of small
perturbations in compressible shear layers with inflection points. By using
linear analysis, we demonstrate that perturbations along the shear plane are most
affected by compressibility. The influence of compressibility gradually
diminishes with increasing obliqueness of the perturbations with respect to the
shear plane. It is demonstrated that the effective gradient Mach number is an
appropriate compressibility parameter. We establish that spanwise perturbations,
orthogonal to the shear plane, are impervious to compressibility effects. Direct
numerical simulations of compressible mixing layers subject to the perturbations
at various obliqueness angles verify the analytical findings.
PMID- 28415342
TI - Griffiths phase on hierarchical modular networks with small-world edges.
AB - The Griffiths phase has been proposed to induce a stretched critical regime that
facilitates self-organizing of brain networks for optimal function. This phase
stems from the intrinsic structural heterogeneity of brain networks, i.e., the
hierarchical modular structure. In this work, the Griffiths phase is studied in
modified hierarchical networks with small-world connections based on the 3
regular Hanoi network. Through extensive simulations, the hierarchical level
dependent inter-module wiring probabilities are identified to determine the
emergence of the Griffiths phase. Numerical results and the complementary
spectral analysis of the relevant networks can be helpful for a deeper
understanding of the essential structural characteristics of finite-dimensional
networks to support the Griffiths phase.
PMID- 28415343
TI - Normal vibrational modes of phospholipid bilayers observed by low-frequency Raman
scattering.
AB - Low-frequency Raman spectra of multilamellar vesicles made either of 1-palmitoyl
2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dipalmitoyl-sn-glycero-3
phosphocholine (DPPC) have been studied in a wide temperature range. Below 0^{?}C
two peaks are found at frequencies around 8-9 and 14-17cm^{-1} and attributed to
the normal vibrational modes of the phospholipid bilayer, which are determined by
the bilayer thickness and stiffness (elastic modulus). The spectral positions of
the peaks depend on the temperature and the bilayer composition. It is suggested
that the ratio of the intensities of the first and second peaks can serve as a
measure of the interleaflet elastic coupling. The addition of cholesterol to the
phospholipid bilayer leads to peak shift and broadening, which may be assigned to
the composition heterogeneities commonly attributed to the lipid raft formation.
PMID- 28415344
TI - Simple noise-reduction method based on nonlinear forecasting.
AB - Nonparametric detrending or noise reduction methods are often employed to
separate trends from noisy time series when no satisfactory models exist to fit
the data. However, conventional noise reduction methods depend on subjective
choices of smoothing parameters. Here we present a simple multivariate noise
reduction method based on available nonlinear forecasting techniques. These are
in turn based on state-space reconstruction for which a strong theoretical
justification exists for their use in nonparametric forecasting. The noise
reduction method presented here is conceptually similar to Schreiber's noise
reduction method using state-space reconstruction. However, we show that
Schreiber's method has a minor flaw that can be overcome with forecasting.
Furthermore, our method contains a simple but nontrivial extension to
multivariate time series. We apply the method to multivariate time series
generated from the Van der Pol oscillator, the Lorenz equations, the Hindmarsh
Rose model of neuronal spiking activity, and to two other univariate real-world
data sets. It is demonstrated that noise reduction heuristics can be objectively
optimized with in-sample forecasting errors that correlate well with actual noise
reduction errors.
PMID- 28415345
TI - Deterministic extinction by mixing in cyclically competing species.
AB - We consider a cyclically competing species model on a ring with global mixing at
finite rate, which corresponds to the well-known Lotka-Volterra equation in the
limit of infinite mixing rate. Within a perturbation analysis of the model from
the infinite mixing rate, we provide analytical evidence that extinction occurs
deterministically at sufficiently large but finite values of the mixing rate for
any species number N>=3. Further, by focusing on the cases of rather small
species numbers, we discuss numerical results concerning the trajectories toward
such deterministic extinction, including global bifurcations caused by changing
the mixing rate.
PMID- 28415346
TI - Synchronization of oscillators through time-shifted common inputs.
AB - Shared upstream dynamical processes are frequently the source of common inputs in
various physical and biological systems. However, due to finite signal
transmission speeds and differences in the distance to the source, time shifts
between otherwise common inputs are unavoidable. Since common inputs can be a
source of correlation between the elements of multi-unit dynamical systems,
regardless of whether these elements are directly connected with one another or
not, it is of importance to understand their impact on synchronization. As a
canonical model that is representative for a variety of different dynamical
systems, we study limit-cycle oscillators that are driven by stochastic time
shifted common inputs. We show that if the oscillators are coupled, time shifts
in stochastic common inputs do not simply shift the distribution of the phase
differences, but rather the distribution actually changes as a result. The best
synchronization is therefore achieved at a precise intermediate value of the time
shift, which is due to a resonance-like effect with the most probable phase
difference that is determined by the deterministic dynamics.
PMID- 28415347
TI - Collisional model of energy dissipation in three-dimensional granular impact.
AB - We study the dynamic process occurring when a granular assembly is displaced by a
solid impactor. The momentum transfer from the impactor to the target is shown to
occur through sporadic, normal collisions of high force carrying grains at the
intruder surface. We therefore describe the stopping force of the impact through
a collisional-based model. To verify the model in impact experiments, we
determine the forces acting on an intruder decelerating through a dense granular
medium by using high-speed imaging of its trajectory. By varying the intruder
shape and granular target, intruder-grain interactions are inferred from the
consequent path. As a result, we connect the drag to the effect of intruder shape
and grain density based on a proposed collisional model.
PMID- 28415348
TI - Delineating parameter unidentifiabilities in complex models.
AB - Scientists use mathematical modeling as a tool for understanding and predicting
the properties of complex physical systems. In highly parametrized models there
often exist relationships between parameters over which model predictions are
identical, or nearly identical. These are known as structural or practical
unidentifiabilities, respectively. They are hard to diagnose and make reliable
parameter estimation from data impossible. They furthermore imply the existence
of an underlying model simplification. We describe a scalable method for
detecting unidentifiabilities, as well as the functional relations defining them,
for generic models. This allows for model simplification, and appreciation of
which parameters (or functions thereof) cannot be estimated from data. Our
algorithm can identify features such as redundant mechanisms and fast time-scale
subsystems, as well as the regimes in parameter space over which such
approximations are valid. We base our algorithm on a quantification of regional
parametric sensitivity that we call 'multiscale sloppiness'. Traditionally, the
link between parametric sensitivity and the conditioning of the parameter
estimation problem is made locally, through the Fisher information matrix. This
is valid in the regime of infinitesimal measurement uncertainty. We demonstrate
the duality between multiscale sloppiness and the geometry of confidence regions
surrounding parameter estimates made where measurement uncertainty is non
negligible. Further theoretical relationships are provided linking multiscale
sloppiness to the likelihood-ratio test. From this, we show that a local
sensitivity analysis (as typically done) is insufficient for determining the
reliability of parameter estimation, even with simple (non)linear systems. Our
algorithm can provide a tractable alternative. We finally apply our methods to a
large-scale, benchmark systems biology model of necrosis factor (NF)-kappaB,
uncovering unidentifiabilities.
PMID- 28415349
TI - Decorrelation correction for nanoparticle tracking analysis of dilute
polydisperse suspensions in bulk flow.
AB - Nanoparticle tracking analysis, a multiprobe single particle tracking technique,
is a widely used method to quickly determine the concentration and size
distribution of colloidal particle suspensions. Many popular tools remove non
Brownian components of particle motion by subtracting the ensemble-average
displacement at each time step, which is termed dedrifting. Though critical for
accurate size measurements, dedrifting is shown here to introduce significant
biasing error and can fundamentally limit the dynamic range of particle size that
can be measured for dilute heterogeneous suspensions such as biological
extracellular vesicles. We report a more accurate estimate of particle mean
square displacement, which we call decorrelation analysis, that accounts for
correlations between individual and ensemble particle motion, which are
spuriously introduced by dedrifting. Particle tracking simulation and
experimental results show that this approach more accurately determines particle
diameters for low-concentration polydisperse suspensions when compared with
standard dedrifting techniques.
PMID- 28415350
TI - Simple unified view of branching process statistics: Random walks in balanced
logarithmic potentials.
AB - We revisit the problem of deriving the mean-field values of avalanche exponents
in systems with absorbing states. These are well known to coincide with those of
unbiased branching processes. Here we show that for at least four different
universality classes (directed percolation, dynamical percolation, the voter
model or compact directed percolation class, and the Manna class of stochastic
sandpiles) this common result can be obtained by mapping the corresponding
Langevin equations describing each of them into a random walker confined to the
origin by a logarithmic potential. We report on the emergence of nonuniversal
continuously varying exponent values stemming from the presence of small external
driving - that might induce avalanche merging - that, to the best of our
knowledge, has not been noticed in the past. Many of the other results derived
here appear in the literature as independently derived for individual
universality classes or for the branching process itself. Still, we believe that
a simple and unified perspective as the one presented here can help (1) clarify
the overall picture, (2) underline the superuniversality of the behavior as well
as the dependence on external driving, and (3) avoid the common existing
confusion between unbiased branching processes (equivalent to a random walker in
a balanced logarithmic potential) and standard (unconfined) random walkers.
PMID- 28415351
TI - Gross-Pitaevski map as a chaotic dynamical system.
AB - The Gross-Pitaevski map is a discrete time, split-operator version of the Gross
Pitaevski dynamics in the circle, for which exponential instability has been
recently reported. Here it is studied as a classical dynamical system in its own
right. A systematic analysis of Lyapunov exponents exposes strongly chaotic
behavior. Exponential growth of energy is then shown to be a direct consequence
of rotational invariance and for stationary solutions the full spectrum of
Lyapunov exponents is analytically computed. The present analysis includes the
"resonant" case, when the free rotation period is commensurate to 2pi, and the
map has countably many constants of the motion. Except for lowest-order
resonances, this case exhibits an integrable-chaotic transition.
PMID- 28415352
TI - Self-averaging in the random two-dimensional Ising ferromagnet.
AB - We study sample-to-sample fluctuations in a critical two-dimensional Ising model
with quenched random ferromagnetic couplings. Using replica calculations in the
renormalization group framework we derive explicit expressions for the
probability distribution function of the critical internal energy and for the
specific heat fluctuations. It is shown that the disorder distribution of
internal energies is Gaussian, and the typical sample-to-sample fluctuations as
well as the average value scale with the system size L like ~Llnln(L). In
contrast, the specific heat is shown to be self-averaging with a distribution
function that tends to a delta peak in the thermodynamic limit L->infinity. While
previously a lack of self-averaging was found for the free energy, we here obtain
results for quantities that are directly measurable in simulations, and
implications for measurements in the actual lattice system are discussed.
PMID- 28415353
TI - Noise-induced symmetry breaking far from equilibrium and the emergence of
biological homochirality.
AB - The origin of homochirality, the observed single-handedness of biological amino
acids and sugars, has long been attributed to autocatalysis, a frequently assumed
precursor for early life self-replication. However, the stability of homochiral
states in deterministic autocatalytic systems relies on cross-inhibition of the
two chiral states, an unlikely scenario for early life self-replicators. Here we
present a theory for a stochastic individual-level model of autocatalytic
prebiotic self-replicators that are maintained out of thermal equilibrium.
Without chiral inhibition, the racemic state is the global attractor of the
deterministic dynamics, but intrinsic multiplicative noise stabilizes the
homochiral states. Moreover, we show that this noise-induced bistability is
robust with respect to diffusion of molecules of opposite chirality, and systems
of diffusively coupled autocatalytic chemical reactions synchronize their final
homochiral states when the self-replication is the dominant production mechanism
for the chiral molecules. We conclude that nonequilibrium autocatalysis is a
viable mechanism for homochirality, without imposing additional nonlinearities
such as chiral inhibition.
PMID- 28415354
TI - Stochastic resonance across bifurcation cascades.
AB - The classical setting of stochastic resonance is extended to account for
parameter variations leading to transitions between a unique stable state,
bistability, and multistability regimes, across singularities of various kinds.
Analytic expressions for the amplitude and the phase of the response in terms of
key parameters are obtained. The conditions for optimal responses are derived in
terms of the bifurcation parameter, the driving frequency, and the noise
strength.
PMID- 28415355
TI - Numerical study of continuous and discontinuous dynamical phase transitions for
boundary-driven systems.
AB - The existence and search for thermodynamic phase transitions is of unfading
interest. In this paper, we present numerical evidence of dynamical phase
transitions occurring in boundary-driven systems with a constrained integrated
current. It is shown that certain models exhibit a discontinuous transition
between two different density profiles and a continuous transition between a time
independent and a time-dependent profile. We also verified that the Kipnis
Marchioro-Presutti model exhibits no phase transitions in a range much larger
than previously explored.
PMID- 28415356
TI - Nonspherical liquid droplet falling in air.
AB - The dynamics of an initially nonspherical liquid droplet falling in air under the
action of gravity is investigated via three-dimensional numerical simulations of
the Navier-Stokes and continuity equations in the inertial regime. The surface
tension is considered to be high enough so that a droplet does not undergo
breakup. Vertically symmetric oscillations which decay with time are observed for
low inertia. The amplitude of these oscillations increases for high Gallilei
numbers and the shape asymmetry in the vertical direction becomes prominent. The
reason for this asymmetry has been attributed to the higher aerodynamic inertia.
Moreover, even for large inertia, no path deviations or oscillations are
observed.
PMID- 28415357
TI - Dense crystalline packings of ellipsoids.
AB - An ellipsoid, the simplest nonspherical shape, has been extensively used as a
model for elongated building blocks for a wide spectrum of molecular, colloidal,
and granular systems. Yet the densest packing of congruent hard ellipsoids, which
is intimately related to the high-density phase of many condensed matter systems,
is still an open problem. We discover an unusual family of dense crystalline
packings of self-dual ellipsoids (ratios of the semiaxes alpha:sqrt[alpha]:1),
containing 24 particles with a quasi-square-triangular (SQ-TR) tiling arrangement
in the fundamental cell. The associated packing density phi exceeds that of the
densest known SM2 crystal [ A. Donev et al., Phys. Rev. Lett. 92, 255506
(2004)10.1103/PhysRevLett.92.255506] for aspect ratios alpha in (1.365, 1.5625),
attaining a maximal phi~0.75806... at alpha=93/64. We show that the SQ-TR phase
derived from these dense packings is thermodynamically stable at high densities
over the aforementioned alpha range and report a phase diagram for self-dual
ellipsoids. The discovery of the SQ-TR crystal suggests organizing principles for
nonspherical particles and self-assembly of colloidal systems.
PMID- 28415358
TI - Hamiltonian and Godunov structures of the Grad hierarchy.
AB - The time evolution governed by the Boltzmann kinetic equation is compatible with
mechanics and thermodynamics. The former compatibility is mathematically
expressed in the Hamiltonian and Godunov structures, the latter in the structure
of gradient dynamics guaranteeing the growth of entropy and consequently the
approach to equilibrium. We carry all three structures to the Grad reformulation
of the Boltzmann equation (to the Grad hierarchy). First, we recognize the
structures in the infinite Grad hierarchy and then in several examples of finite
hierarchies representing extended hydrodynamic equations. In the context of
Grad's hierarchies, we also investigate relations between Hamiltonian and Godunov
structures.
PMID- 28415359
TI - Experimental investigation of the effect of thresholding on temporal statistics
of avalanches.
AB - Avalanchelike behavior reflected in power-law statistics is a ubiquitous property
of extended systems addressed in a number of generic models. The paper presents
an experimental investigation of the effect of thresholding on the statistics of
durations and waiting times between avalanches using acoustic emission
accompanying unstable plastic deformation. It is found that durations of acoustic
events obey power-law statistical distributions robust against thresholding. The
quiescent time distributions follow the Poisson law for low threshold values.
Both these results corroborate the hypothesis that plastic deformation is akin to
the phenomena associated with self-organized criticality (SOC), often advanced on
the basis of power-law amplitude statistics. Increasing the threshold height
enforces deviation from the Poisson distributions toward apparent power-law
behavior. Such a thresholding effect may hinder the experimental determination of
SOC-like dynamics because of the inevitable noise.
PMID- 28415360
TI - Mapping current fluctuations of stochastic pumps to nonequilibrium steady states.
AB - We show that current fluctuations in a stochastic pump can be robustly mapped to
fluctuations in a corresponding time-independent nonequilibrium steady state. We
thus refine a recently proposed mapping so that it ensures equivalence of not
only the averages, but also optimal representation of fluctuations in currents
and density. Our mapping leads to a natural decomposition of the entropy
production in stochastic pumps similar to the "housekeeping" heat. As a
consequence of the decomposition of entropy production, the current fluctuations
in weakly perturbed stochastic pumps are shown to satisfy a universal bound
determined by the steady state entropy production.
PMID- 28415361
TI - Fundamental structural characteristics of planar granular assemblies: Self
organization and scaling away friction and initial state.
AB - The microstructural organization of a granular system is the most important
determinant of its macroscopic behavior. Here we identify the fundamental factors
that determine the statistics of such microstructures, using numerical
experiments to gain a general understanding. The experiments consist of preparing
and compacting isotropically two-dimensional granular assemblies of polydisperse
frictional disks and analyzing the emergent statistical properties of quadrons
the basic structural elements of granular solids. The focus on quadrons is
because the statistics of their volumes have been found to display intriguing
universal-like features [T. Matsushima and R. Blumenfeld, Phys. Rev. Lett. 112,
098003 (2014)PRLTAO0031-900710.1103/PhysRevLett.112.098003]. The dependence of
the structures and of the packing fraction on the intergranular friction and the
initial state is analyzed, and a number of significant results are found. (i) An
analytical formula is derived for the mean quadron volume in terms of three
macroscopic quantities: the mean coordination number, the packing fraction, and
the rattlers fraction. (ii) We derive a unique, initial-state-independent
relation between the mean coordination number and the rattler-free packing
fraction. The relation is supported numerically for a range of different systems.
(iii) We collapse the quadron volume distributions from all systems onto one
curve, and we verify that they all have an exponential tail. (iv) The nature of
the quadron volume distribution is investigated by decomposition into conditional
distributions of volumes given the cell order, and we find that each of these
also collapses onto a single curve. (v) We find that the mean quadron volume
decreases with increasing intergranular friction coefficients, an effect that is
prominent in high-order cells. We argue that this phenomenon is due to an
increased probability of stable irregularly shaped cells, and we test this using
a herewith developed free cell analytical model. We conclude that, in principle,
the microstructural characteristics are governed mainly by the packing procedure,
while the effects of intergranular friction and initial states are details that
can be scaled away. However, mechanical stability constraints suppress slightly
the occurrence of small quadron volumes in cells of order >=6, and the magnitude
of this effect does depend on friction. We quantify in detail this dependence and
the deviation it causes from an exact collapse for these cells. (vi) We argue
that our results support strongly the view that ensemble granular statistical
mechanics does not satisfy the uniform measure assumption of conventional
statistical mechanics. Results (i)-(iv) have been reported in the aforementioned
reference, and they are reviewed and elaborated on here.
PMID- 28415362
TI - Subphase transitions in first-order aggregation processes.
AB - In this paper, we investigate the properties of aggregation transitions in the
context of generic coarse-grained homopolymer systems. By means of parallel
replica-exchange Monte Carlo methods, we perform extensive simulations of systems
consisting of up to 20 individual oligomer chains with five monomers each. Using
the tools of the versatile microcanonical inflection-point analysis, we show that
the aggregation transition is a first-order process consisting of a sequence of
subtransitions between intermediate structural phases. We unravel the properties
of these intermediate phases by collecting and analyzing their individual
contributions towards the density of states of the system. The central theme of
this systematic study revolves around translational entropy and its role in the
striking phenomena of missing intermediate phases. We conclude with a brief
discussion of the scaling properties of the transition temperature and the latent
heat.
PMID- 28415363
TI - Phase-field model of oxidation: Equilibrium.
AB - A phase-field model of an oxide relevant to corrosion resistant alloys for film
thicknesses below the Debye length L_{D}, where charge neutrality in the oxide
does not occur, is formulated. The phase-field model is validated in the Wagner
limit using a sharp interface Gouy-Chapman model for the electrostatic double
layer. The phase-field simulations show that equilibrium oxide films below the
Wagner limit are charged throughout due to their inability to electrostatically
screen charge over the length of the film, L. The character of the defect and
charge distribution profiles in the oxide vary depending on whether reduced
oxygen adatoms are present on the gas-oxide interface. The Fermi level in the
oxide increases for thinner films, approaching the Fermi level of the metal in
the limit L/L_{D}->0, which increases the driving force for adsorbed oxygen
reduction at the gas-oxide interface.
PMID- 28415364
TI - Interfacial adsorption in two-dimensional pure and random-bond Potts models.
AB - We use Monte Carlo simulations to study the finite-size scaling behavior of the
interfacial adsorption of the two-dimensional square-lattice q-states Potts
model. We consider the pure and random-bond versions of the Potts model for
q=3,4,5,8, and 10, thus probing the interfacial properties at the originally
continuous, weak, and strong first-order phase transitions. For the pure systems
our results support the early scaling predictions for the size dependence of the
interfacial adsorption at both first- and second-order phase transitions. For the
disordered systems, the interfacial adsorption at the (disordered induced)
continuous transitions is discussed, applying standard scaling arguments and
invoking findings for bulk critical properties. The self-averaging properties of
the interfacial adsorption are also analyzed by studying the infinite limit-size
extrapolation of properly defined signal-to-noise ratios.
PMID- 28415365
TI - Analyses of kinetic glass transition in short-range attractive colloids based on
time-convolutionless mode-coupling theory.
AB - For short-range attractive colloids, the phase diagram of the kinetic glass
transition is studied by time-convolutionless mode-coupling theory (TMCT). Using
numerical calculations, TMCT is shown to recover all the remarkable features
predicted by the mode-coupling theory for attractive colloids: the glass-liquid
glass reentrant, the glass-glass transition, and the higher-order singularities.
It is also demonstrated through the comparisons with the results of molecular
dynamics for the binary attractive colloids that TMCT improves the critical
values of the volume fraction. In addition, a schematic model of three control
parameters is investigated analytically. It is thus confirmed that TMCT can
describe the glass-glass transition and higher-order singularities even in such a
schematic model.
PMID- 28415366
TI - Statistical mechanics of the triple contact line.
AB - We outline a statistical mechanics of the triple gas-solid-liquid contact line on
a rough plane. The analysis regards the neighborhood of the line as a solid
dotted with cavities. It adopts the simplest mean-field statistical mechanics, in
which each cavity is either full or empty, while being connected to near
neighbors by thin necks. The theory predicts equilibrium angles for advance and
recession in terms of the Young contact angle and the joint statistical
distribution of two quantifiable geometrical parameters representing specific
neck cross-section and specific cavity opening. It attributes contact angle
hysteresis to first-order phase transitions among adjacent cavities, as they
collectively imbibe or reject liquid. It also calculates the potential energy
barriers that hysteresis erects against overcoming contact line pinning. By
determining whether the phase transitions can release latent energy, this ab
initio analysis distinguishes six regimes, including two metastable recession
states. We compare predictions with data for superhydrophobia on microscopic
rods; for hysteresis in the "Wenzel state"; and for variations of the advancing
contact angle with surface energies of the liquid.
PMID- 28415367
TI - Collective phase reduction of globally coupled noisy dynamical elements.
AB - We formulate a theory for the collective phase reduction of globally coupled
noisy dynamical elements exhibiting macroscopic rhythms. We first transform the
Langevin-type equation that represents a group of globally coupled noisy
dynamical elements into the corresponding nonlinear Fokker-Planck equation and
then develop the phase reduction method for limit-cycle solutions to the
nonlinear Fokker-Planck equation. The theory enables us to describe the
collective dynamics of a group of globally coupled noisy dynamical elements by a
single degree of freedom called the collective phase. As long as the group
collectively exhibits macroscopic rhythms, the theory is applicable even when the
coupling and noise are strong; it is also independent of the assumption that each
element of the group is a self-sustained oscillator. We also provide a simple and
accurate numerical algorithm for the collective phase description method and
numerically illustrate the theory using a group of globally coupled noisy
FitzHugh-Nagumo elements.
PMID- 28415368
TI - Role of thermal disequilibrium on natural convection in porous media: Insights
from pore-scale study.
AB - The present study investigates the role of thermal nonequilibrium on natural
convection in a fluid-saturated porous medium heated from below. We conduct high
resolution direct numerical simulation at the pore scale in a two-dimensional
regular porous structure by means of the thermal lattice-Boltzmann method (LBM).
We perform a combination of linear stability analysis of continuum-scale heat
transfer models, and pore-scale and continuum-scale simulations to study the role
of thermal conductivity contrasts among phases on natural convection. The
comparison of pore-scale lattice-Boltzmann simulations with linear stability
analysis reveals that traditional continuum-scale models fail to capture the
correct onset of convection, convection mode, and heat transfer when the thermal
conductivity of the solid obstacles does not match that of the fluid.
PMID- 28415369
TI - From solitons to rogue waves in nonlinear left-handed metamaterials.
AB - In the present work, we explore soliton and roguelike wave solutions in the
transmission line analog of a nonlinear left-handed metamaterial. The
nonlinearity is expressed through a voltage-dependent, symmetric capacitance
motivated by recently developed ferroelectric barium strontium titanate thin-film
capacitor designs. We develop both the corresponding nonlinear dynamical lattice
and its reduction via a multiple scales expansion to a nonlinear Schrodinger
(NLS) model for the envelope of a given carrier wave. The reduced model can
feature either a focusing or a defocusing nonlinearity depending on the frequency
(wave number) of the carrier. We then consider the robustness of different types
of solitary waves of the reduced model within the original nonlinear left-handed
medium. We find that both bright and dark solitons persist in a suitable
parametric regime, where the reduction to the NLS model is valid. Additionally,
for suitable initial conditions, we observe a rogue wave type of behavior that
differs significantly from the classic Peregrine rogue wave evolution, including
most notably the breakup of a single Peregrine-like pattern into solutions with
multiple wave peaks. Finally, we touch upon the behavior of generalized members
of the family of the Peregrine solitons, namely, Akhmediev breathers and
Kuznetsov-Ma solitons, and explore how these evolve in the left-handed
transmission line.
PMID- 28415370
TI - Bubblelike structures generated by activation of internal shape modes in two
dimensional sine-Gordon line solitons.
AB - Nonlinear waves that collide with localized defects exhibit complex behavior.
Apart from reflection, transmission, and annihilation of an incident wave, a
local inhomogeneity can activate internal modes of solitons, producing many
impressive phenomena. In this work we investigate a two-dimensional sine-Gordon
model perturbed by a family of localized forces. We observed the formation of
bubblelike and droplike structures due to local internal shape mode
instabilities. We describe the formation of such structures on the basis of a one
dimensional theory of activation of internal modes of sine-Gordon solitons. An
interpretation of the observed phenomena, in the context of phase transition
theory, is given. Implications in Josephson junctions with a current dipole
device are discussed.
PMID- 28415371
TI - Simple bounds on fluctuations and uncertainty relations for first-passage times
of counting observables.
AB - Recent large deviation results have provided general lower bounds for the
fluctuations of time-integrated currents in the steady state of stochastic
systems. A corollary are so-called thermodynamic uncertainty relations connecting
precision of estimation to average dissipation. Here we consider this problem but
for counting observables, i.e., trajectory observables which, in contrast to
currents, are non-negative and nondecreasing in time (and possibly symmetric
under time reversal). In the steady state, their fluctuations to all orders are
bound from below by a Conway-Maxwell-Poisson distribution dependent only on the
averages of the observable and of the dynamical activity. We show how to obtain
the corresponding bounds for first-passage times (times when a certain value of
the counting variable is first reached) and their uncertainty relations. Just
like entropy production does for currents, dynamical activity controls the bounds
on fluctuations of counting observables.
PMID- 28415372
TI - Ultrametricity of optimal transport substates for multiple interacting paths over
a square lattice network.
AB - We model a set of point-to-point transports on a network as a system of
polydisperse interacting self-avoiding walks (SAWs) over a finite square lattice.
The ends of each SAW may be located both at random, uniformly distributed,
positions or with one end fixed at a lattice corner. The total energy of the
system is computed as the sum over all SAWs, which may represent either the time
needed to complete the transport over the network, or the resources needed to
build the networking infrastructure. We focus especially on the second aspect by
assigning a concave cost function to each site to encourage path overlap. A
simulated annealing optimization, based on a modified Berg-Foerster-Aragao de
Carvalho-Caracciolo-Froehlich (BFACF) algorithm developed for polymers, is used
to probe the complex conformational substate structure at zero temperature. We
characterize the average cost gains (and path-length variations) for increasing
polymer density with respect to a Dijkstra routing and find a nonmonotonic
behavior as recently found for random networks. We observe the emergence of
ergodicity breaking and of nontrivial overlap distributions among replicas when
switching from a convex to a concave cost function (e.g., x^{gamma}, where x
represents the node overlap). Finally, we show that the space of ground states
for gamma<1 is compatible with an ultrametric structure, as seen in many complex
systems such as some spin glasses.
PMID- 28415373
TI - How turbulence fronts induce plasma spin-up.
AB - A calculation which describes the spin-up of toroidal plasmas by the radial
propagation of turbulence fronts with broken parallel symmetry is presented. The
associated flux of parallel momentum is calculated by using a two-scale direct
interaction approximation in the weak turbulence limit. We show that fluctuation
momentum spreads faster than mean flow momentum. Specifically, the turbulent flux
of wave momentum is stronger than the momentum pinch. The scattering of
fluctuation momentum can induce edge-core coupling of toroidal flows, as observed
in experiments.
PMID- 28415374
TI - Explicit calculation of nuclear-magnetic-resonance relaxation rates in small
pores to elucidate molecular-scale fluid dynamics.
AB - Nuclear-magnetic-resonance (NMR) spin-lattice (T_{1}^{-1}) and spin-spin (T_{2}^{
1}) relaxation rate measurements can act as effective nondestructive probes of
the nanoscale dynamics of ^{1}H spins in porous media. In particular, fast-field
cycling T_{1}^{-1} dispersion measurements contain information on the dynamics of
diffusing spins over time scales spanning many orders of magnitude. Previously
published experimental T_{1}^{-1} dispersions from a plaster paste, synthetic
saponite, mortar, and oil-bearing shale are reanalyzed using a model and
associated theory which describe the relaxation rate contributions due to the
interaction between spin ensembles in quasi-two-dimensional pores. Application of
the model yields physically meaningful diffusion correlation times for all
systems. In particular, the surface diffusion correlation time and the surface
desorption time take similar values for each system, suggesting that surface
mobility and desorption are linked processes. The bulk fluid diffusion
correlation time is found to be two to five times the value for the pure liquid
at room temperature for each system. Reanalysis of the oil-bearing shale yields
diffusion time constants for both the oil and water constituents. The shale is
found to be oil wetting and the water T_{1}^{-1} dispersion is found to be
associated with aqueous Mn^{2+} paramagnetic impurities in the bulk water. These
results escalate the NMR T_{1}^{-1} dispersion measurement technique as the
primary probe of molecular-scale dynamics in porous media yielding diffusion
parameters and a wealth of information on pore morphology.
PMID- 28415375
TI - Nonlinear Monte Carlo model of superdiffusive shock acceleration with magnetic
field amplification.
AB - Fast collisionless shocks in cosmic plasmas convert their kinetic energy flow
into the hot downstream thermal plasma with a substantial fraction of energy
going into a broad spectrum of superthermal charged particles and magnetic
fluctuations. The superthermal particles can penetrate into the shock upstream
region producing an extended shock precursor. The cold upstream plasma flow is
decelerated by the force provided by the superthermal particle pressure gradient.
In high Mach number collisionless shocks, efficient particle acceleration is
likely coupled with turbulent magnetic field amplification (MFA) generated by the
anisotropic distribution of accelerated particles. This anisotropy is determined
by fast particle transport, making the problem strongly nonlinear and multiscale.
Here, we present a nonlinear Monte Carlo model of collisionless shock structure
with superdiffusive propagation of high-energy Fermi accelerated particles
coupled to particle acceleration and MFA, which affords a consistent description
of strong shocks. A distinctive feature of the Monte Carlo technique is that it
includes the full angular anisotropy of the particle distribution at all
precursor positions. The model reveals that the superdiffusive transport of
energetic particles (i.e., Levy-walk propagation) generates a strong quadruple
anisotropy in the precursor particle distribution. The resultant pressure
anisotropy of the high-energy particles produces a nonresonant mirror-type
instability that amplifies compressible wave modes with wavelengths longer than
the gyroradii of the highest-energy protons produced by the shock.
PMID- 28415376
TI - Streamwise localization of traveling wave solutions in channel flow.
AB - Channel flow of an incompressible fluid at Reynolds numbers above 2400 possesses
a number of different spatially localized solutions that approach laminar flow
far upstream and downstream. We use one such relative time-periodic solution,
which corresponds to a spatially localized version of a Tollmien-Schlichting
wave, to illustrate how the upstream and downstream asymptotics can be computed
analytically. In particular, we show that for these spanwise uniform states the
asymptotics predict the exponential localization that has been observed for
numerically computed solutions of several canonical shear flows but never
properly understood theoretically.
PMID- 28415377
TI - Delay-induced depinning of localized structures in a spatially inhomogeneous
Swift-Hohenberg model.
AB - We report on the dynamics of localized structures in an inhomogeneous Swift
Hohenberg model describing pattern formation in the transverse plane of an
optical cavity. This real order parameter equation is valid close to the second
order critical point associated with bistability. The optical cavity is
illuminated by an inhomogeneous spatial Gaussian pumping beam and subjected to
time-delayed feedback. The Gaussian injection beam breaks the translational
symmetry of the system by exerting an attracting force on the localized
structure. We show that the localized structure can be pinned to the center of
the inhomogeneity, suppressing the delay-induced drift bifurcation that has been
reported in the particular case where the injection is homogeneous, assuming a
continuous wave operation. Under an inhomogeneous spatial pumping beam, we
perform the stability analysis of localized solutions to identify different
instability regimes induced by time-delayed feedback. In particular, we predict
the formation of two-arm spirals, as well as oscillating and depinning dynamics
caused by the interplay of an attracting inhomogeneity and destabilizing time
delayed feedback. The transition from oscillating to depinning solutions is
investigated by means of numerical continuation techniques. Analytically, we use
an order parameter approach to derive a normal form of the delay-induced Hopf
bifurcation leading to an oscillating solution. Additionally we model the
interplay of an attracting inhomogeneity and destabilizing time delay by
describing the localized solution as an overdamped particle in a potential well
generated by the inhomogeneity. In this case, the time-delayed feedback acts as a
driving force. Comparing results from the later approach with the full Swift
Hohenberg model, we show that the approach not only provides an instructive
description of the depinning dynamics, but also is numerically accurate
throughout most of the parameter regime.
PMID- 28415378
TI - Drag law for an intruder in granular sediments.
AB - We investigate the drag experienced by a spherical intruder moving through a
medium consisting of granular hydrogels immersed in water as a function of its
depth, size, and speed. The medium is observed to display a yield stress with a
finite force required to move the intruder in the quasistatic regime at low
speeds before rapidly increasing at high speeds. In order to understand the
relevant time scales that determine drag, we estimate the inertial number I given
by the ratio of the time scales required to rearrange grains due to the
overburden pressure and imposed shear and the viscous number J given by the ratio
of the time scales required to sediment grains in the interstitial fluid and
imposed shear. We find that the effective friction MU_{e} encountered by the
intruder can be parametrized by I=sqrt[rho_{g}/P_{p}]v_{i}, where rho_{g} is the
density of the granular hydrogels, v_{i} is the intruder speed, and P_{p} is the
overburden pressure due to the weight of the medium, over a wide range of I where
the Stokes number St=I^{2}/J?1. We then show that MU_{e} can be described by the
function MU_{e}(I)=MU_{0}+alphaI^{beta}, where MU_{0}, alpha, and beta are
constants that depend on the medium. This formula can be used to predict the drag
experienced by an intruder of a different size at a different depth in the same
medium as a function of its speed.
PMID- 28415379
TI - Chimeras and clusters in networks of hyperbolic chaotic oscillators.
AB - We show that chimera states, where differentiated subsets of synchronized and
desynchronized dynamical elements coexist, can emerge in networks of hyperbolic
chaotic oscillators subject to global interactions. As local dynamics we employ
Lozi maps, which possess hyperbolic chaotic attractors. We consider a globally
coupled system of these maps and use two statistical quantities to describe its
collective behavior: the average fraction of elements belonging to clusters and
the average standard deviation of state variables. Chimera states, clusters,
complete synchronization, and incoherence are thus characterized on the space of
parameters of the system. We find that chimera states are related to the
formation of clusters in the system. In addition, we show that chimera states
arise for a sufficiently long range of interactions in nonlocally coupled
networks of these maps. Our results reveal that, under some circumstances,
hyperbolicity does not impede the formation of chimera states in networks of
coupled chaotic systems, as it had been previously hypothesized.
PMID- 28415380
TI - miR-98 inhibits expression of TWIST to prevent progression of non-small cell lung
cancers.
AB - Evidence is mounting that micro RNAs (miRNAs) play a critical role in tumor
development. However, the role of miRNAs in lung cancer progression remains
largely unknown. Herein, we found that miR-98 significantly impaired in patients
with non-small cell lung cancers (NSCLC) and was a novel regulator of NSCLC
progression. Patients with high miR-98 expression had a longer overall survival
than with low miR-98 expression (p=0.0495). miR-98 expression level inversely
correlated with TWIST mRNA level in 71 clinical tissue specimens of NSCLC
(p<0.01). Luciferase assay demonstrated that miR-98 interacted binding sites in
the TWIST 3'-UTR and reduced expression of TWIST, resulting in repression of cell
migration and invasion via impeding TWIST-mediated EMT. Furthermore, introduction
of synthetic miR-98 caused growth arrest by inactivating TWIST-Akt-CDK4/CDK6.
Meanwhile, miR-98 mimic induced apoptosis by targeting TWIST-Akt axis. In a
conclusion, these observations imply that miR-98 may act as a tumor suppressor in
NSCLC to decelerate NSCLC aggressiveness by inhibiting TWIST expression.
PMID- 28415381
TI - Biocompatibility study on Ni-free Ti-based and Zr-based bulk metallic glasses.
AB - Safety and reliability are crucial issues for medical instruments and implants.
In the past few decays, bulk metallic glasses (BMGs) have drawn attentions due to
their superior mechanical properties, good corrosion resistance, antibacterial
and good biocompatibility. However, most Zr-based and Ti-based BMGs contain Ni as
an important element which is prone to human allergy problem. In this study, the
Ni-free Ti-based and Zr-based BMGs, Ti40Zr10Cu36Pd14, and Zr48Cu36Al8Ag8, were
selected for systematical evaluation of their biocompatibility. Several
biocompatibility tests, co-cultural with L929 murine fibroblast cell line, were
carried out on these two BMGs, as well as the comparison samples of Ti6Al4V and
pure Cu. The results in terms of cellular adhesion, cytotoxicity, and metallic
ion release affection reveal that the Ti40Zr10Cu36Pd14 BMG and Ti6Al4V exhibit
the optimum biocompatibility; cells still being attached on the petri dish with
good adhesion and exhibiting the spindle shape after direct contact test.
Furthermore, the Ti40Zr10Cu36Pd14 BMG showed very low Cu ion release level, in
agreement with the MTT results. Based on the current findings, it is believed
that Ni-free Ti-based BMG can act as an ideal candidate for medical implant.
PMID- 28415382
TI - Alkali-etching growth of nest-like Ag@mTiO2 hierarchical nanostructures and their
potential applications.
AB - Porous nanomaterials have attracted extensive interests in adsorption, catalysis,
biosensors, and biomedicine due to their high surface area, well-defined pore
structure and tunable pore size. However, how to obtain porous nanomaterials of
desirable component and unique structure with multifunctionalities and synergetic
properties is still a great challenge. In this work, a novel nest-like Ag@mTiO2
hierarchical nanostructure with Ag nanoparticle as the core and a mesoporous
crystalline TiO2 as the protective shell was successfully prepared by layer-by
layer assembly technique and alkali-etching hydrothermal route. By simply
changing the conditions of alkali etching, different nanostructures could be
obtained, such as core-shell or rattle type. In the process, the thickness of
coating silica layer and TiO2 shell both played important roles for the formation
of desired nanostructures. The as-prepared products had a large specific surface
area of 301m2/g and a tailored TiO2 outer shell. Raman spectra results showed
perfect SERS signal of the tags enhanced and remained good stability even after
one month. Doxycycline (Doxy) was chosen to evaluate their drug loading and
controlled release properties. The results indicated that the obtained Ag@mTiO2
nanoparticles exhibited good biocompatibility and excellent drug-loading
capacity. Consequently, they are also expected to serve as ideal candidates for
more potential applications including photocatalysis, drug controlled release,
biosensor and cell imaging, etc.
PMID- 28415383
TI - Preparation and characterization of a novel degradable nano
hydroxyapatite/poly(lactic-co-glycolic) composite reinforced with bamboo fiber.
AB - It is a promising and challenging to achieve an ideal poly (lactic-co-glycolic)
(PLGA)-based composite. In this paper, bamboo fiber (BF) was firstly designed to
incorporate into nano-hydroxyapatite/PLGA (n-HA/PLGA) composite, and a series of
novel biodegradable BF/n-HA/PLGA ternary composites with different BF amounts
(0wt%, 5wt%, 10wt% and 20wt%) were prepared by solution mixing method. The effect
of BF content on the crystallization behavior, interface structure and mechanical
property of BF/n-HA/PLGA ternary composite was investigated by X-ray diffraction
pattern (XRD), differential scanning calorimeter (DSC) and scanning electron
microscope (SEM), comparing with pure PLGA and n-HA/PLGA composite. The results
showed that BF further promoted the crystallization of PLGA acting as a
heterogeneous nucleation agent, and the addition of 10wt% BF was the best benefit
to promote the crystallization. However, the higher addition content of BF caused
more agglomeration in n-HA/PLGA matrix, which decreased gradually the mechanical
properties of the BF/n-HA/PLGA composite. In conclusion, the addition content of
5wt% BF to n-HA/PLGA matrix was an appropriate proportion, which can achieved the
best mechanical reinforce effectiveness, suggesting that BF/n-HA/PLGA composite
had more potential in biomedical application than n-HA/PLGA composite.
PMID- 28415384
TI - Preparation and characterization of expanded graphite/metal oxides for
antimicrobial application.
AB - Composite materials based on expanded graphite (EG) and metal oxide (MO)
particles was prepared by an explosive combustion and blending method. The
objective of the study was to develop EG impregnated with metal oxide
particulates (Ag2O, CuO and ZnO) and evaluate the level of protection the
materials conferred against biological agents. The physical properties of the
EG/MO composites were examined using SEM, EDX and XRD spectroscopy, and the
results indicated that the MO particles were incorporated into the EG matrix
after impregnation. The antimicrobial activities of the EG/MO composites against
Gram-positive bacteria, Gram-negative bacteria and Bacillus anthracis were
investigated using zone of inhibition, minimum inhibitory concentration (MIC),
minimum bactericidal concentration (MBC) and plate-counting methods. EG/Ag2O
exhibited a stronger antibacterial activity than EG/CuO and EG/ZnO, with a MIC of
0.3mg/mL and a MBC of 0.5mg/mL. To the best of our knowledge, few studies have
demonstrated that EG/MO composites can inhibit the growth of Bacillus anthracis
adhered cells, thus preventing the process of biofilm formation. Nanoscale metal
oxides display enhanced reactive properties toward bacteria due to their high
surface area, large number of highly reactive edges, corner defect sites and high
surface to volume ratio.
PMID- 28415385
TI - Antitubercular activity of ZnO nanoparticles prepared by solution combustion
synthesis using lemon juice as bio-fuel.
AB - In this study, we report the synthesis, structural and morphological
characteristics of zinc oxide (ZnO) nanoparticles using solution combustion
synthesis method where lemon juice was used as the fuel. In vitro anti-tubercular
activity of the synthesized ZnO nanoparticles and their biocompatibility studies,
both in vitro and in vivo were carried out. The synthesized nanoparticles showed
inhibition of Mycobacterium tuberculosis H37Ra strain at concentrations as low as
12.5MUg/mL. In vitro cytotoxicity study performed with normal mammalian cells
(L929, 3T3-L1) showed that ZnO nanoparticles are non-toxic with a Selectivity
Index (SI) >10. Cytotoxicity performed on two human cancer cell lines DU-145 and
Calu-6 indicated the anti-cancer activity of ZnO nanoparticles at varied
concentrations. Results of blood hemolysis indicated the biocompatibility of ZnO
nanoparticles. Furthermore, in vivo toxicity studies of ZnO nanoparticles
conducted on Swiss albino mice (for 14days as per the OECD 423 guidelines) showed
no evident toxicity.
PMID- 28415386
TI - Modification and evaluation of micro-nano structured porous bacterial cellulose
scaffold for bone tissue engineering.
PMID- 28415387
TI - Dextrose modified flexible tasar and muga fibroin films for wound healing
applications.
AB - This paper is focused on preparation and characterization of regenerated muga and
tasar fibroin flexible films from cocoon using ionic liquid. These flexible muga
and tasar fibroin films were prepared by incorporating dextrose (5 to 15% w/w) as
plasticizer. The mechanical, thermal, physical, morphological and biological
properties of dextrose plasticized muga and tasar fibroin films were
characterized. These plasticized films showed higher elongation at break as well
as water holding capacity as compared to the un-plasticized films. The surface
roughness and water absorbance capacity of the dextrose plasticized films were
higher than un-plasticized films, which results in improved adherence and
proliferation of L929 fibroblast cells. Gentamicin loaded plasticized muga and
tasar fibroin films showed slightly higher rate of release as compared to un
plasticized films. The biodegradability of dextrose plasticized films was
significantly higher as compared to their respective counterpart. The
regeneration of flexible muga and tasar silk fibroin films pave the way to expand
potential use of non-mulberry in the field of biomedical such as wound dressing.
PMID- 28415388
TI - Targeted delivery of docetaxel via Pi-Pi stacking stabilized dendritic polymeric
micelles for enhanced therapy of liver cancer.
AB - Delivery of taxane-based chemotherapeutics including Docetaxel (DTX) by
conventional polymeric micelles still suffers from insufficient stability and
rapid premature release during the circulation, which limits their targeting and
anticancer efficiency. To conquer these challenges, we developed a novel DTX
loaded Pi-Pi stacking-stabilized dendritic polymeric micelle for targeted therapy
of liver cancer. This dendritic polymeric micelle, referred to DPM-DTX-cRGD, was
self-assembled from DTX and biodegradable dendritic block copolymers
Poly(amidoamine)-poly(gamma-benzyl-l-Glutamate)-b-polyethylene glycol-cRGD (PAM
PBLG-b-PEG-cRGD). DPM-DTX-cRGD held robust stability due to its covalent
dendritic structure and would load abundant DTX with excellent retention via Pi
Pi stacking between DTX and the aromatic groups of the PBLG segments. The
cellular uptake studies demonstrated that the cRGD-conjugated dendritic polymeric
micelle (DPM) exhibited much higher cellular uptake in human liver cancer HepG2
cells than non-targeted DPM. The MTT assay also confirmed that DPM-DTX-cRGD
caused much greater cytotoxicity than non-targeted DPM-DTX and a clinically
available DTX formulation (Taxotere(r)). Therefore, this DPM-DTX-cRGD provides a
novel attractive approach for targeted therapy of liver cancer.
PMID- 28415389
TI - Antibacterial, osteogenic, and angiogenic activities of SrTiO3 nanotubes embedded
with Ag2O nanoparticles.
AB - Biomedical titanium (Ti) implants with good anti-infective, osteogenic, and
angiogenic properties are in great demand. SrTiO3 nanotubes (NTs) are embedded
with silver oxide (Ag2O) nanoparticles (NPs) (denoted as NT-Sr-Ag) by a
hydrothermal treatment of TiO2 NTs containing Ag2O NPs (denoted as NT-Ag) in a
Sr(OH)2 solution. The morphology, composition, microstructure, ion release
phenomenon, as well as antibacterial, osteogenic, and angiogenic activities are
investigated in details. During the hydrothermal treatment, the amorphous TiO2 in
the NTs morphs into cubic SrTiO3 gradually and the ordered nanotubular
architecture is preserved. Some Ag2O NPs are incorporated into the structure
although some of them dissolve in the solution. Long-term bacterial resistance
against Staphylococcus aureus is observed as a result of the prolonged and
controllable Ag+ release. NT-Sr-Ag can also release Sr2+ similarly to stimulate
osteoblasts to secrete the vascular endothelial growth factor (VEGF). Both the
released Sr2+ and secreted VEGF upregulate the alkaline phosphatase (ALP)
activity and extracellular matrix mineralization of osteoblasts. Furthermore,
better angiogenic activity is observed when endothelial cells are cultured in NT
Sr-Ag conditioned media when compared with that in NT-Ag conditioned media, which
is believed to be ascribed to the positive regulation of VEGF secretion of Sr2+.
NT-2Sr-Ag and NT-3Sr-Ag (Hydrothermal treatment for 2 and 3h, respectively)
exhibit excellent antibacterial, osteogenic, and angiogenic activities and are
promising in biomedical implants.
PMID- 28415390
TI - Synthesis, spectroscopic and DNA binding ability of CoII, NiII, CuII and ZnII
complexes of Schiff base ligand (E)-1-(((1H-benzo[d]imidazol-2
yl)methylimino)methyl)naphthalen-2-ol. X-ray crystal structure determination of
cobalt (II) complex.
AB - A novel Schiff base ligand, (E)-1-(((1H-benzo[d]imidazol-2
yl)methylimino)methyl)naphthalen-2-ol (HL), has been designed and synthesized in
addition to its metal chelates [Co(L)2].l2H2O, [Ni(L)Cl.(H2O)2].5H2O, [Cu(L)Cl]
and [Zn(L)(CH3COO)]. The structures of the isolated compounds have been confirmed
and identified by means of different spectral and physicochemical techniques
including CHN analysis, 1H &13C NMR, mass spectral analysis, molar conductivity
measurement, UV-Vis, infrared, magnetic moment in addition to TGA technique. The
infrared spectral results ascertained that the ligand acts as monobasic
tridentate binding to the metal centers via deprotonated hydroxyl oxygen,
azomethine and imidazole nitrogen atoms. The UV-Vis, magnetic susceptibility and
molar conductivity data implied octahedral geometry for Co(II) & Ni(II)
complexes, tetrahedral for Zn(II) complex and square planar for Cu(II) complex. X
ray structural analysis of Co(II) complex 1 has been reported and discussed.
Moreover, the type of interaction between the ligand & its complexes towards
salmon sperm DNA (SS-DNA) has been examined by the measurement of absorption
spectra and viscosity which confirmed that the ligand and its complexes interact
with DNA via intercalation interaction as concluded from the values of binding
constants (Kb).
PMID- 28415391
TI - Biological activity evaluation of magnesium fluoride coated Mg-Zn-Zr alloy in
vivo.
AB - AIM: To explore the biodegradable characteristics and biological properties,
which could promote new bone formation, of MgF2 coated magnesium alloy (Mg-3wt%Zn
0.5wt%Zr) in rabbits. METHODS: Magnesium alloy with MgF2 coating was made and the
MgF2/Mg-Zn-Zr was implanted in the femoral condyle of rabbits. Twelve healthy
adult Japanese white rabbits in weight of 2.8-3.2kg were averagely divided into
A(Mg-Zn-Zr) group and B(MgF2/MgZn-Zr) group. Indexes such as microstructural
evolution, SEM scan, X-ray, Micro-CT and mechanical properties were observed and
detected at 1th day, 2th, 4th, 8th, 12th, 24th week after implantation. RESULTS:
Low-density regions occurred around the cancellous bone, and the regions
gradually expanded during the 12weeks after implantation. The implant was
gradually absorbed from 12 to 24weeks. The density of surrounding cancellous bone
increased compared with the 12th week data. The degradation rate of B group was
lower than that of A group (P<0.01), while the density of the surrounding
cancellous bone increased more evenly. In B group, SEM images after 12weeks
showed the rich bone tissues on the alloy surface that were attached by active
fibers. Micro-CT also presented alloy residue potholes on the surfaces of alloy
combinated with bone tissues. Additionally, the trabecular bone had relatively
integrated structures with surrounding cavities. CONCLUSIONS: MgF2 can
effectively decrease the degradation rate of Mg-Zn-Zr in vivo. Mg-Zn-Zr coated
with MgF2 can effectively inhibit the corrosion, and delay the release of
magnesium ions. The biological properties of the coating itself presented good
biocompatibility and bioactivity.
PMID- 28415392
TI - Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for
tissue engineering: Preparation and in vitro evaluation.
AB - Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical
applications, including tissue engineering, due to their biocompatibility, high
water solubility, low protein adsorption, and chemical stability. However, non
charged surface of PVA-based hydrogels is not optimal for cell adhesion and
spreading. Here, cross-linked macroporous hydrogels based on low molecular weight
acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol
groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity,
charged groups were introduced to the hydrogel composition. For this purpose, Acr
PVA was copolymerized with either negatively charged acrylic acid (AA) or
positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A
surface charge of the obtained hydrogels was found to be in function of the co
monomer type and content. Confocal microscopy observations confirmed that
adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal
stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were
better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA
monomer content from 5 to 15mol% resulted in the enhancement of cell viability
which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non
modified Acr-PVA hydrogel sample.
PMID- 28415393
TI - The relationship between particle morphology and rheological properties in
injectable nano-hydroxyapatite bone graft substitutes.
AB - Biomaterials composed of hydroxyapatite (HA) are currently used for the treatment
of bone defects resulting from trauma or surgery. However, hydroxyapatite
supplied in the form of a paste is considered a very convenient medical device
compared to the materials where HA powder and liquid need to be mixed immediately
prior to the bone treatment during surgery. In this study we have tested a series
of hydroxyapatite (HA) pastes with varying microstructure and different
rheological behaviour to evaluate their injectability and biocompatibility. The
particle morphology and chemical composition were evaluated using HRTEM, XRD and
FTIR. Two paste-types were compared, with the HA particles of both types being
rod shaped with a range of sizes between 20 and 80nm while differing in the
particle aspect ratio and the degree of roundness or sharpness. The pastes were
composed of pure HA phase with low crystallinity. The rheological properties were
evaluated and it was determined that the pastes behaved as shear-thinning, non
Newtonian liquids. The difference in viscosity and yield stress between the two
pastes was investigated. Surprisingly, mixing of these pastes at different ratios
did not alter viscosity in a linear manner, providing an opportunity to produce a
specific viscosity by mixing the two materials with different characteristics.
Biocompatibility studies suggested that there was no difference in vitro cell
response to either paste for primary osteoblasts, bone marrow mesenchymal stromal
cells, osteoblast-like cells, and fibroblast-like cells. This class of
nanostructured biomaterial has significant potential for use as an injectable
bone graft substitute where the properties may be tailored for different clinical
indications.
PMID- 28415394
TI - Ultra-sensitive detection of ibuprofen (IBP) by electrochemical aptasensor using
the dendrimer-quantum dot (Den-QD) bioconjugate as an immobilization platform
with special features.
AB - This study describes a high-performance electrochemical aptasensor which is
employed to detect Ibuprofen (IBP) as a painkiller drug by using a novel platform
as an integrated sensing interface. In order to make the aptasensor, the Den-QD
bioconjugate was immobilized on the surface of a GC electrode and followed the
Apt was incubated on this surface. The incubation of the IBP on the aptasensor
surface and the formation of the Apt/IBP complex, led to a hindered electron
transfer reaction on the sensing surface, which decreased the peak current of the
redox probe. Under the optimum condition, the assay had two dynamic ranges with a
detection limit down to 333fM. The developed aptasensor reliably detects IBP in a
real sample. Our results demonstrated that the proposed strategy has many
advantages and the Den-QD bioconjugate may become a promising nanocomposite for
the electrochemical sensing applications.
PMID- 28415395
TI - Drug kinetics release from Eudragit - Tenofovir@SiOC tablets.
AB - A novel drug release system has been obtained in form of tablets from Eudragit(r)
RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active
carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative
purposes. The porous silicon oxycarbide presents a bimodal mesopore size
distribution that is maintained after functionalization with amino groups. We
have studied the adsorption kinetics and adsorption equilibrium when the
materials are loaded with tenofovir and, in all cases, pseudo-second order
kinetics and Langmuir isotherm have been revealed as the most representative
models describing the kinetic and thermodynamic parameters. Besides, the
tenofovir adsorption on these materials turns out to be a favorable process. In
vitro release of tenofovir has been studied in simulated vaginal medium by
applying different release models. Continuous tenofovir release for >20days has
been obtained for the SiOC material functionalized with amine groups. We
concluded that the drug release occurs in two steps that involve a drug diffusion
step through the material pores and diffusion through the swollen polymer. The
interactions between the tenofovir drug and de amine groups of the functionalized
silicon oxycarbide also play an important role in the release process.
PMID- 28415396
TI - Role of silver/zinc oxide in affecting de-adhesion strength of Staphylococcus
aureus on polymer biocomposites.
AB - A single-cell force spectroscopy is utilized to characterize the dynamics of the
transient interaction (0-10s) between alive Staphylococcus aureus and ultra-high
molecular weight polyethylene (UHMWPE). Adhesion force of bacteria upon addition
of antibacterial additives (i.e. silver (Ag) nanoparticles and zinc oxide (ZnO)
micro-rods) has been evaluated. Addition of Ag and ZnO reduces the colony forming
units (CFUs) from 93+/-7 (UHMWPE) to 23+/-5 (U+3wt.% Ag+3wt.% ZnO) on 10*10mm2
area of sample surface. Presence of ZnO causes increase in the surface free
energy from 29.1 (UHMWPE) to 32.3mJ/m2 (UHMWPE+1wt.% ZnO) and 32.3mJ/m2 for
U+3wt.% ZnO whereas due to Ag the surface free energy decreased to 28.3mJ/m2 and
28.4mJ/m2 for UHMWPE+1wt.% Ag and U+3wt.% Ag respectively. At a contact time of
10s bacterial adhesion on U+1wt.% Ag+1wt.% ZnO, U+3wt.% Ag and U+3wt.% Ag+3wt.%
ZnO showed lowest adhesion forces, ~2.6nN, ~2.9nN and ~3.2N respectively as
compared to neat UHMWPE (~4nN) due to a lower surface free energies, but U+1wt.%
Ag and U+1wt.% ZnO and U+3wt.% ZnO show higher adhesion force due their higher
surface free energy. Ag nanoparticles reduce the live bacteria count whereas ZnO
reduces the bacterial retention and combination of both acts synergistically so
the count of live bacteria as well as total bacterial density reduced in U-Ag-ZnO
composite samples.
PMID- 28415397
TI - Surface-modified bioresorbable electrospun scaffolds for improving
hemocompatibility of vascular grafts.
AB - The replacement of small-diameter vessels is one of the main challenges in tissue
engineering. Moreover, the surface modification of small-diameter vascular grafts
(SDVG) is a key factor in the success of the therapy due to their increased
thrombogenicity and infection susceptibility caused by the lack of a functional
endothelium. In this work, electrospun scaffolds were prepared from blends of
poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) with a composition
designed to perform as SDVG inner layer. The scaffolds were then successfully
surface-modified with heparin following two different strategies that rely on
grafting of heparin to either PLLA or PHD functional groups. Both strategies
afforded high heparin density, being higher for urethane methodology. The
functionalized scaffolds did not cause hemolysis and inhibited platelet adhesion
to a large extent. However, lysozyme/heparin-functionalized scaffolds obtained
through urethane methodology achieved the highest platelet attachment inhibition.
The increase in hydrophilicity and water absorption of the surface-functionalized
nanostructures favored adhesion and proliferation of human adipose-derived stem
cells. Heparinized surfaces conjugated with lysozyme presented microbial
hydrolysis activity dependent on heparin content. Overall, a better performance
obtained for urethane-modified scaffold, added to the fact that no chain scission
is involved in urethane methodology, makes the latter the best choice for surface
modification of PLLA/PHD 50/50 electrospun scaffolds. Scaffolds functionalized by
this route may perform as advanced components of SDVG suitable for vascular
tissue engineering, exhibiting biomimetic behavior, avoiding thrombi formation
and providing antimicrobial features.
PMID- 28415398
TI - Combinatorial delivery of superparamagnetic iron oxide nanoparticles (gammaFe2O3)
and doxorubicin using folate conjugated redox sensitive multiblock polymeric
nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells.
AB - Redox sensitive, folate conjugated multiblock polymeric system of (-PLGA-PEG-PLGA
urethane-ss-) demonstrated self-assembly into stable nanoplatforms. The polymeric
nanocarriers were encapsulated with doxorubicin and highly crystalline gammaFe2O3
superparamagnetic iron oxide nanoparticles (SPIONs), for co-delivery of the same
to cancer cells, with average particle size of ~170nm and zeta potential of ~
33mV. Furthermore, the designed formulation was evaluated for protein adsorption,
hemo-cytocompatibility and stability. Glutathione (GSH) induced redox sensitivity
of the nanocarriers was depicted by ~4.47 fold increase in drug release in the
presence of 10mM GSH. In vitro cellular uptake studies of the designed
nanocarriers showed synergistic cytotoxic effect in folate overexpressing cells
(HeLa and MDA-MB-231), after subjecting the cells to radio frequency (RF) induced
hyperthermia (~43 degrees C). Negligible effect of the combinatorial therapy was
observed in normal cells (L929). The developed polymeric system depicted facile
synthesis, reproducibility and potential for achieving combinatorial and targeted
delivery of drug and SPIONs to cancer cells. This combinatorial approach can help
in achieving better therapeutic effect with minimal side effects of chemotherapy.
PMID- 28415399
TI - Novel keratin modified bacterial cellulose nanocomposite production and
characterization for skin tissue engineering.
AB - As it is known that bacterial cellulose (BC) is a biocompatible and natural
biopolymer due to which it has a large set of biomedical applications. But still
it lacks some desired properties, which limits its uses in many other
applications. Therefore, the properties of BC need to be boosted up to an
acceptable level. Here in this study for the first time, a new natural
nanocomposite was produced by the incorporating keratin (isolated from human
hair) to the BC (produced by Acetobacter xylinum) to enhance dermal fibroblast
cells' attachment. Two different approaches were used in BC based nanocomposite
production: in situ and post modifications. BC/keratin nanocomposites were
characterized using SEM, FTIR, EDX, XRD, DSC and XPS analyses. Both production
methods have yielded successful results for production of BC based nanocomposite
containing keratin. In vitro cell culture experiments performed with human skin
keratinocytes and human skin fibroblast cells indicate the potential of the novel
BC/keratin nanocomposites for use in skin tissue engineering.
PMID- 28415400
TI - Antibacterial and cytocompatible nanotextured Ti surface incorporating silver via
single step hydrothermal processing.
AB - Nanosurface modification of Titanium (Ti) implants and prosthesis is proved to
enhance osseointegration at the tissue-implant interface. However, many of these
products lack adequate antibacterial capability, which leads to implant
loosening. As a curative strategy, in this study, nanotextured Ti substrates
embedded with silver nanoparticles were developed through a single step
hydrothermal processing in an alkaline medium containing silver nitrate at
different concentrations (15, 30 and 75MUM). Scanning electron micrographs
revealed a non-periodically oriented nanoleafy structure on Ti (TNL) decorated
with Ag nanoparticles (nanoAg), which was verified by XPS, XRD and EDS analysis.
This TNLAg substrate proved to be mechanically stable upon nanoindentation and
nanoscratch tests. Silver ions at detectable levels were released for a period of
~28days only from substrates incorporating higher nanoAg content. The samples
demonstrated antibacterial activity towards both Escherichia coli and
Staphylococcus aureus, with a more favorable response to the former.
Simultaneously, Ti substrates incorporating nanoAg at all concentrations
supported the viability, proliferation and osteogenic differentiation of
mesenchymal stem cells. Overall, nanoAg incorporation into surface modified Ti
via a simple one-step thermochemical method is a favorable strategy for producing
implants with dual characteristics of antibacterial activity and cell
compatibility.
PMID- 28415401
TI - A new 2-amino-3-pynanopyrane-3- carbonitrile derivative for electrocatalytic
oxidation and determination of hydrazine.
AB - A noble glassy carbon electrode modified with Au nanoparticles and 2-amino-4-(3,4
dihydroxyphenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3
carbonitrile, was fabricated for electrocatalytic determination of hydrazine
(AuNPs/APP/GCE). Large over-potential and interference of some species are two
limitation factors for the determination of hydrazine at bare electrode. This
modified electrode is able to shift a signal to the negative potential, and can
amplify the oxidation current of hydrazine by 28.0 time, compared to bare
electrode. The diffusion coefficient, D, and the heterogeneous rate constant, kh,
for the oxidation of hydrazine at the modified surface were calculated by
chronoamperometric studies. Finally, the fabricated sensor was agreeably utilized
for the determination of hydrazine in real samples.
PMID- 28415402
TI - Fattigation-platform theranostic nanoparticles for cancer therapy.
AB - A new conceptual nanoparticle consisting of a silica-coated iron oxide magnetic
core and a fattigation-based biocompatible shell with oleic acid and hydrophilic
protein (gelatin). The prepared particle can be a useful theranostics platform
material for diagnostic imaging and as a drug delivery system. Oleic acid and
gelatin were conjugated on the silica-coated magnetic nanoparticle surface to
provide three primary functionalities: 1) enhancing biocompatibility and
solubility in aqueous solution and providing the ability to incorporate
hydrophobic chemical drugs into the shell for delivery, 2) improving treatment
response magnetic monitoring as a diagnostic agent with low nanotoxicity, and 3)
increasing anticancer efficacy owing to the controlled release of the
incorporated drug in cells and in an animal model. We prepared magnetic-silica
nanoparticles with super-paramagnetic properties, which are utilized as a T2
weighted magnetic resonance imaging agent. After formation of an oleic acid
gelatin shell, the prepared materials exhibited high loading capacity for a
hydrophobic anticancer drug (paclitaxel). Our particle platform system exhibited
higher therapeutic efficacy and lower toxicological effects in vitro and in an in
vivo cancer model than a clinically available chemo-drug (Taxol(r)). Our findings
strongly suggest that this nanoparticle system can serve as a platform for cancer
therapy by the incorporation of chemical drugs.
PMID- 28415404
TI - Macrophage phagocytosis of biomedical Mg alloy degradation products prepared by
electrochemical method.
AB - Biomedical Mg alloy is promising for its widespread use clinically. In vitro and
in vivo studies showed that the degradation products of biomedical Mg alloy were
composed of O, P, Ca, Mg and other alloying elements. However, little is known
about the metabolism of the degradation products. In this study, the in vitro
macrophage phagocytosis of the degradation products of a biomedical Mg-Nd-Zn-Zr
alloy was directly observed. This result affirms the necessity to investigate the
long-term fate of Mg alloy degradation products in physiological environments.
Besides, an electrochemical method was proposed to prepare enough amount of
degradation products in vitro efficiently.
PMID- 28415403
TI - Design and synthesis of reduced graphene oxide based supramolecular scaffold: A
benign microbial resistant network for enzyme immobilization and cell growth.
AB - The present study describes the synthesis, characterization and biological
application of reduced graphene oxide - chitosan (GC) based benign supramolecular
scaffold (SMS). Various spectroscopic and microscopic analyses established the
supramolecular interaction in between rGO and chitosan. The active performance of
the developed material towards microbial resistivity, in vitro cell growth and as
a scaffold for enzyme immobilizing matrix illustrates its unique implementation.
Immobilization of polyphenol oxidase (PPO) onto GC lowers the Michaelis- Menten
constant (Km) value and facilitates to achieve maximum velocity at low substrate
concentration. Importantly GC shows no noteworthy cytotoxicity towards Wistar rat
macrophage cells. Moreover, incorporation of gold nanoparticle further
strengthens the microbial resistance properties of GC as well as improves its
biocompatibility by reducing cytotoxicity. Therefore these unique features may
inspire it to appear in large scale for industrial utilization.
PMID- 28415405
TI - Incorporation of glass-reinforced hydroxyapatite microparticles into poly(lactic
acid) electrospun fibre mats for biomedical applications.
AB - Tissue engineering is constantly evolving towards novel materials that mimic the
properties of the replaced injured tissue or organ. A hybrid electrospun membrane
of electroactive poly(l-acid lactic) (PLLA) polymer with glass reinforced
hydroxyapatite (Bonelike(r)) microparticles placed among the polymer fibres in a
morphology like "islands in the sea" was processed. The incorporation of 60 to
80wt% Bonelike(r) bone grafts granules with <=150MUm into the polymer solution
lead to an amorphous polymeric fibre membranes, and a decrease of the average
polymer fibre diameter from 550+/-150nm for neat PLA down to 440+/-170nm for the
hybrid composite. The presence of Bonelike(r) in the polymer mats reduced the
activation energy for thermal degradation from 134kJ.mol-1, obtained for the neat
PLLA membranes down to 71kJ.mol-1, calculated for the hybrid composite membranes.
In vitro cell culture results suggest that the developed processing method does
not induce cytotoxic effects in MG 63 osteoblastic cells, and creates an
environment that enhances cell proliferation, when compared to the neat PLLA
membrane. The simplicity and scalability of the processing method suggests a
large application potential of this novel hybrid polymer-microparticles fibre
membranes for bone regenerative medicine.
PMID- 28415406
TI - PCL foamed scaffolds loaded with 5-fluorouracil anti-cancer drug prepared by an
eco-friendly route.
AB - This study describes a new preparation method, which combines freeze drying and
supercritical CO2 foaming approaches, for the preparation of drug delivery
scaffolds of polycaprolactone loaded with 5-fluorouracil, an anti-cancer drug,
with low solubility in scCO2. It is a principal objective of this work to design
a scCO2 strategy to reduce 5-Fu solubility limitations in its homogeneous
distribution into a PCL scaffold through the design of an innovative processing
method. The design of this process is considered valuable for the development of
clean technology in pharmacy and medicine, since most of the active agents have a
null solubility in scCO2.Supercritical CO2 is used as a blowing agent to induce
polymer foaming by means of the low temperature pressure quench process. The
resulting samples have been prepared under different operational conditions
focused on enhancing the performance of the release process. In this case, design
of experiments (DOE) was considered for a more comprehensive and systematic
optimization of the product. In particular, drug amount, equals to 4.8 or 9.1wt%,
process temperature, of 45 or 50 degrees C and depressurization rate, equals to
0.1MPas-1 or 2MPas-1 were selected as the factors to be investigated by a three
factor at two-level full factorial design. Samples were characterized to
establish porosity data, drug loading percentage and, especially, release profile
chromatographically monitored. Results from DOE have concluded which are the best
samples providing a sustained drug release for several days, which may be of
great interest to develop materials for tissue engineering and sustained release
applications.
PMID- 28415407
TI - Formulation by design based risperidone nano soft lipid vesicle as a new strategy
for enhanced transdermal drug delivery: In-vitro characterization, and in-vivo
appraisal.
AB - The present study was designed to formulate and optimize transdermal risperidone
soft lipid vesicles. The formulation optimized with phospholipid, safranal and
ethanol were incorporated as permeation and absorption enhancers. The optimized
risperidone soft lipid vesicle was further evaluated for skin irritation study,
in-vivo pharmacokinetic study and locomotor activity. Three factor three level
Box-Behnken design (BBD) was used to statistically optimize soft lipid vesicle
using safranal (A), ethanol (B)and phospholipid (C) as independent variable,
while their effect was observed for vesicle size (Y1), entrapment efficiency (Y2)
and flux (Y3). The optimized risperidone soft lipid vesicle (Ris-opt) showed
nanometric vesicle size, high entrapment efficiency and marked enhancement in
transdermal flux. The extent of absorption from Ris-opt was greater when compared
to oral suspension with relative bioavailability of 177%. The histopathological
evaluation revealed developed formulation did not showed skin irritation compared
to standard irritant. The significant findings presented here encourage further
studies with risperidone soft lipid vesicles for treatment of schizophrenia.
PMID- 28415408
TI - Role of cellulose functionality in bio-inspired synthesis of nano bioactive
glass.
AB - In search of abundant cheaper natural polymer for bio-inspired bioactive glass
nanoparticles synthesis, cellulose and its derivatives have been considered as a
template. Different templates explored in the present studies are pure cellulose,
methyl cellulose and amine grafted cellulose. To the best of our knowledge, for
the first time of the considered templates, pure cellulose and amine grafted
cellulose results in in situ nano particulate composite formation while
interestingly methyl cellulose proves to be an excellent sacrificial template for
the synthesis of uniform bioglass nanoparticles of diameter in the range of 55nm.
Further, viscoelastic measurements were carried out using dynamic mechanical
analyzer. Herein, an attempt has been made to establish structure-mechanical
relationship based on the templates. Moreover, in vitro bioactivity is also
observed to be affected by the nature of the template molecule used for the
synthesis of bioactive glass.
PMID- 28415409
TI - In vitro antiherpes effect of C-glycosyl flavonoid enriched fraction of Cecropia
glaziovii encapsulated in PLGA nanoparticles.
AB - In this work is reported a novel and promising approach for the preparation of C
glycosylflavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) loaded PLGA
nanoparticles (NP) with antiherpes properties. The purpose of this study was to
evaluate and to compare the effect of two nonionic surfactants (poloxamer 188
(PLU) and polyvinyl alcohol (PVA)), and also an emulsion stabilized by solid
particles of cellulose nanocrystal (CNC) in place of surfactants. The
characterization of these nanoparticles was in terms of size, polydispersity
index, zeta potential, morphology, thermogravimetric analysis (TGA), loading
capacity and percent yield. Since TGA analysis revealed thermo stability
especially for NP-PLU, this formulation was selected for the evaluation of drug
release profile, cytotoxicity and antiherpes activity. The drug delivery profile
demonstrated a sustained release through the polymer structure and a significant
reduction of the polymer molecular weight at 21-day period. The cytotoxicity of
these nanoparticles was determined on Vero cells, and the selected formulation
did not exhibit cytotoxicity even at the highest tested concentration. The
results demonstrated a potential antiherpetic effect of the EFF-Cg loaded NP at
48h of testing. In summary, EFF-Cg loaded NP exhibited a promising system for the
effective drug delivery in the treatment of herpes infections.
PMID- 28415410
TI - Biodegradable polyurethane micelles with pH and reduction responsive properties
for intracellular drug delivery.
AB - Polyurethane micelles with disulfide linkage located at the interface of
hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug
release profiles. However, the payloads could not be released completely. The
occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG
coronas was considered as the reason for the incomplete release. To verify the
above hypothesis and to develop a new polyurethane based micelles with dual
stimuli respond properties and controllable location of pH and reduction
responsive groups in the PU main chains, a tertiary amine was incorporated into
the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and
pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide
linkages located between the hydrophilic PEG segment and the hydrophobic PCL
segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the
hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen
as mode hydrophobic drug to evaluate the loading and redox triggered release
profiles of the PU micelles. It was demonstrated that PU-SS-N micelles
disassembled instantly at the presence of 10mM GSH and at an acidic environment
(pH=5.5), which resulted the nearly complete release (~90%) of the payloads
within 48h, while about ~70% PTX was released from PU-SS-I and PU-SS-N micelles
at neutral environment (pH=7.4) with the presence of 10mM GSH. The rapid and
complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will
be a promising anticancer drug delivery system to ensure sufficient drug
concentration to kill the cancer cells and to prevent the emergency of MDR. The
in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also
assessed in H460 and HepG2 cells.
PMID- 28415411
TI - Quality by Design approach for an in situ gelling microemulsion of Lorazepam via
intranasal route.
AB - The present study illustrates the application of the concept of Quality by Design
for development, optimization and evaluation of Lorazepam loaded microemulsion
containing ion responsive In situ gelator gellan gum and carbopol 934. A novel
approach involving interactions between surfactant and polymer was employed to
achieve controlled drug release and reduced mucociliary clearance. Microemulsion
formulated using preliminary solubility study and pseudo ternary phase diagrams
showed significantly improved solubilization capacity of Lorazepam with 54.31+/
6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and
concentration of gelling agent on the drug release and viscosity of microemulsion
gel (MEG) was evaluated using a 32 full factorial design. The gel of optimized
formulation (MEG1) showed a drug release up to 6h of 97.32+/-1.35% of total drug
loaded. The change in shear-dependent viscosity for different formulations on
interaction with Simulated Nasal Fluid depicts the crucial role of surfactant
polymer interactions on the gelation properties along with calcium ions binding
on the polymer chains. It is proposed that the surfactant-polymer interactions in
the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic
groups of the polymers used, provides exceptional ME stability and adhesion
properties. Compared with the marketed formulation, optimized MEG showed improved
pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher
release for MEG compared to microemulsion and drug solution. MEG showed higher
flux and permeation across goat nasal mucosa. According to the study, it could be
concluded that formulation would successfully provide the rapid onset of action,
and decrease the mucociliary clearance due to formation of in situ gelling
mucoadhesive system.
PMID- 28415412
TI - Graphene oxide modified single-use electrodes and their application for
voltammetric miRNA analysis.
AB - The modification of graphene oxide (GO) onto the surfaces of chemically activated
pencil graphite electrodes (PGEs) was performed herein, and then these electrodes
were applied for the first time on voltammetric monitoring of miRNAs. The
specific recognition of miRNA-34a, which has been related to Alzheimer disease,
was explored in the presence of DNA-RNA hybridization by using CA/GO/PGEs in
combination with differential pulse voltammetry (DPV) technique. The
characterization of CA/GO/PGE was investigated by cyclic voltammetry (CV),
electrochemical impedance spectroscopy (EIS), and scanning electron microscopy
(SEM). The effect of GO concentration, DNA probe concentration and miRNA-34a
concentration upon to biosensor response was optimized, and accordingly, the
selectivity of miRNA-34a biosensor was tested under the optimum conditions.
PMID- 28415413
TI - Development and characterization of the cisplatin loaded nanofibers for the
treatment of cervical cancer.
AB - A small scale study was carried out to investigate the therapeutic efficacy
cisplatin loaded poly-caprolactone/chitosan composite electrospun nanofibers for
local chemotherapy of cervical cancers in mice. The prepared nanofibers had shown
the sustained release pattern up to one month. Prepared nanofibers were found to
have greater mucoadhesive strength. An orthotopic cervical cancer model was
established by inducing the EAC cell lines in the vaginal mucosa at cervix region
of the mice. Intravaginal administration of the cisplatin loaded nanofibers
showed lesser % cell viability as compared to the plain drug. In vivo studies
showed a better anti-tumour efficacy of prepared nanofibers in animals at 14th
and 21st after the beginning of treatment. Therefore the technique of
electrospinning provides a favourable approach for the targeted delivery of the
anti-cancer drug via vaginal route against cervical cancer.
PMID- 28415414
TI - Bionanocomposite systems based on montmorillonite and biopolymers for the
controlled release of olanzapine.
AB - Olanzapine (OLZ) is a drug that is used in the treatment of schizophrenia and
other psychoses, and it belongs to the thienobenzodiazepine class. The OLZ
molecule has low solubility decreasing bioavailability, but has high permeability
in membrane biological being classified as a Class II drug substance according to
the Biopharmaceutics Classification System. It was reported many side effects of
administering OLZ orally. So, in order to increase the bioavailability of drug
and possibly reducing some of side effects, this paper proposes a new material
able to controllably release the drug in the body. To control the dissolution
rate, this work proposes a system that incorporates the drug into montmorillonite
(MMT) dispersed in a mixture of alginate (ALG) and xanthan gum (XG) biopolymers.
The proposed hybrids and bionanocomposites were characterized by several
physicochemical techniques, including XRD, IR-ATR, TG DTA, SEM-EDS and HPLC. The
characterization data confirmed the intercalation of the OLZ into the MMT by the
ion exchange process, as well as the interaction of the MMT-OLZ with the
biopolymers. The release test, conducted under various pH conditions, showed that
the proposed system exhibited a more controlled drug release than commercial
tablets, indicating that the ALG-XG/MMT-OLZ bionanocomposite can act as a
controlled release system for OLZ.
PMID- 28415415
TI - Curcumin-loaded polysaccharide nanoparticles: Optimization and anticariogenic
activity against Streptococcus mutans.
AB - Curcumin was loaded into different polysaccharide nanoparticles chitosan,
alginate and starch, using the desolvation method. Curcumin-loaded nanoparticles
exhibited enhanced solubility in aqueous solutions comparing with free curcumin.
Effects of formulation parameters such as curcumin concentration and different
volumes of ethanolic solution were affected the particle size and loading
efficiency. Under optimum conditions, curcumin-loaded chitosan, starch and
alginate nanoparticles with mean particles sizes of 66.3, 61.1 and 78.8nm, and
maximum loading efficiencies of 11.9%, 14.3% and 13.35% were achieved,
respectively. Additionally, the minimum inhibitory concentration for chitosan,
starch and alginate nanoparticles against the microorganism, Streptococcus
mutans, were 0.114, 0.204 and 0.204mg/mL, respectively. Curcumin was observed to
release from nanoparticles under physiological pH over a period of 96h. The
effect of curcumin-loaded nanoparticles on S. mutans biofilms was assessed on
dental models. According to the results, curcumin-loaded chitosan nanoparticles
hold promises for being used in dental decay fighting products.
PMID- 28415416
TI - In vitro and in vivo corrosion, mechanical properties and biocompatibility
evaluation of MgF2-coated Mg-Zn-Zr alloy as cancellous screws.
AB - Magnesium (Mg) and its alloys as biodegradable materials have received much
attention in the orthopedics applications; however, the corrosion behavior of
these metals in vivo remains challenging. In this work, a dense and nanoscale
magnesium fluoride (MgF2) coating was deposited on the surface of Mg-Zn-Zr (MZZ)
alloy cancellous screw. The MZZ cancellous screw with MgF2 coating maintained an
integrated shape and high yield tensile stress after 30days immersion in SBF,
comparing with the bare screw. Hydrogen releasing rate of the MZZ samples was
suppressed at a lower level at the initial stage, which is in favour of the
adhesion of the cells. And in vivo experiments indicated that MgF2-coated MZZ
screws presented advantages in cytocompatibility, osteoconductivity and
osteogenesis of cancellous bone in rabbits. Corrosion rate in vivo perfusion
environment increased very slowly with time in long-term study, which was an
opposite trend in vitro static immersion test. Moreover, maximum corrosion rate
(CRmax), a critical calculation method of corrosion rate was introduced to
predict fracture regions of the sample. The MZZ alloy with MgF2 coating possesses
a great potential for clinical applications for internal fracture fixation
repair.
PMID- 28415417
TI - Porous 45S5 Bioglass(r)-based scaffolds using stereolithography: Effect of
partial pre-sintering on structural and mechanical properties of scaffolds.
AB - Scaffolds made from 45S5 Bioglass(r) ceramic (BG) show clinical potential in bone
regeneration due to their excellent bioactivity and ability to bond to natural
bone tissue. However, porous BG scaffolds are limited by their mechanical
integrity and by the substantial volume contractions occurring upon sintering.
This study examines stereolithographic (SLA) methods to fabricate mechanically
robust and porous Bioglass(r)-based ceramic scaffolds, with regular and
interconnected pore networks and using various computer-aided design
architectures. It was found that a diamond-like (DM) architecture gave scaffolds
the most controllable results without any observable closed porosity in the fired
scaffolds. When the pore dimensions of the DM scaffolds of the same porosity
(~60vol%) were decreased from 700 to 400MUm, the compressive strength values
increased from 3.5 to 6.7MPa. In addition, smaller dimensional shrinkage could be
obtained by employing partially pre-sintered bioglass, compared to standard 45S5
Bioglass(r). Scaffolds derived from pre-sintered bioglass also showed marginally
improved compressive strength.
PMID- 28415418
TI - UV-assisted treatment on hydrophobic acrylic IOLs anterior surface with
methacryloyloxyethyl phosphorylcholine: Reducing inflammation and maintaining low
posterior capsular opacification properties.
AB - In order to enhance the surface biocompatibility of hydrophobic acrylic
intraocular lenses (IOLs), the anterior surface was modified through graft
polymerization with methacryloyloxyethyl phosphorylcholine (MPC) initiated by
ultraviolet radiation. Chemical changes on the IOL surface were characterised by
X-ray photoelectron spectroscopy (XPS) to confirm the covalent binding of MPC.
Field emission scanning electron microscopy (FESEM) and atomic force microscopy
(AFM) analysis were used to characterise the morphological changes to the IOL
surface. Static water contact angle (WCA) measurements showed that the
hydrophilicity of the anterior surface was enhanced after grafting with MPC. The
surface biocompatibility of the untreated and Anterior UV-MPC IOLs was compared
with the adhesion behaviour of macrophages in vitro. The degree of posterior
capsule opacification (PCO) of untreated, anterior treated, and posterior treated
IOLs was evaluated by observing the behaviour of lens epithelial cells (LECs)
between the IOL optic portion and type IV collagen. Results suggest that the MPC
modified anterior surface resisted the attachment of macrophages. However, MPC
grafted onto the posterior surface enhanced the migration of LECs between the IOL
optic and type IV collagen, which may result in severe PCO. In conclusion, our
Anterior UV-MPC IOLs may reduce postoperative inflammation while maintaining the
low PCO rates of hydrophobic acrylic IOLs.
PMID- 28415419
TI - LSP/MAO composite bio-coating on AZ80 magnesium alloy for biomedical application.
AB - A composite bio-coating was fabricated on AZ80 magnesium (Mg) alloy by using
micro-arc oxidation (MAO) under the pretreatment of laser shock peening (LSP) in
order to improve the bio-corrosion resistance and the mechanical integrity. LSP
treatment could induce grain refinement and compressive residual stress field on
the surface of material. MAO bio-coating was grown in alkaline electrolyte with
hydroxyapatite (HA, Ca10(PO4)6(OH)2) to improve the biological properties of the
material. The microstructure, element and phase composition for untreated based
material (BM) and treated samples (LSP layer, MAO bio-coating and LSP/MAO
composite bio-coating) were investigated by transmission electron microscopy
(TEM), scanning electron microscope (SEM), energy dispersion spectroscopy (EDS)
and X-ray diffraction (XRD). Electrochemical tests and slow strain rate tensile
(SSRT) tests were used to evaluate the corrosion resistance and the stress
corrosion susceptibility in simulated body fluid (SBF). The results indicated
that LSP/MAO composite bio-coating can not only improve the corrosion resistance
of Mg alloy substrate evidently but also increase the mechanical properties in
SBF compared to LSP layer and MAO bio-coating. Mg alloy treated by LSP/MAO
composite technique should be better suited as biodegradable orthopedic implants.
PMID- 28415420
TI - In-vitro cell adhesion and proliferation of adipose derived stem cell on
hydroxyapatite composite surfaces.
AB - The goal of this work was to enhance the mechanical strength and fracture
toughness of brittle hydroxyapatite (HAP) by reinforcing it with nanocomposites
such as graphene oxide (GO), carbon nanotubes (CNT) and Titania. The goal was
also to evaluate the cytotoxicity and the cellular adhesion/proliferation of
these composites. The composites were characterized for their crystallinity,
functionality, morphology and mechanical properties. Altering the composition by
adding 1wt% GO and CNT significantly altered the wettability, hardness and
roughness. Further, X-ray diffraction (XRD), Fourier transform infrared
spectroscopy (FITR) and X-ray photoelectron spectroscopy (XPS) results confirm
the crystal structure, bulk chemical composition and surface elemental
composition respectively of the composites. The bulk hardness of HAP with CNT was
significantly higher than that of HAP. The wettability of HAP with GO was
significantly lower than that of HAP with GO and Titania. Adipose Derived Stem
Cells (ADSCs) were used for this study to evaluate cytotoxicity and viability.
HAP with CNT and HAP with CNT and Titania were found to be least cytotoxic
compared to other composites as evaluated by Lactate Dehydrogenase (LDH) assay
and alamarBlue assay. ADSC adhesion and proliferation was investigated after 1, 4
and 7days of culture using fluorescence microscopy. All the composites nurtured
ADSC adhesion and proliferation, however, distinct morphological changes were
observed by using Scanning Electron Microscopy (SEM). Overall, these composites
have the potential to be used as bone graft substitutes.
PMID- 28415421
TI - Simple synthesis of hierarchical AuPt alloy nanochains for construction of highly
sensitive hydrazine and nitrite sensors.
AB - Herein, a single-step co-reduction aqueous route was designed for preparation of
hierarchical AuPt alloy nanochains, firstly using amprolium hydrochloride as a
new stabilizing agent and structure-director. The morphology, structure,
composition, and size of the products were characterized by a series of
technique. The growth mechanism of AuPt nanochains was discussed in details. The
AuPt nanochains modified glassy carbon electrode showed the improved analytical
performances for determination of nitrite and hydrazine. The linear ranges of
nitrite are 0.5-366.4MUM and 466.4-2666.4MUM for the two segments, and the
detection limit is 0.03MUM (S/N=3). The linear ranges of hydrazine are 5.0
116.4MUM and 166.4-2666.4MUM for the two segments, along with the low detection
limit of 0.26MUM (S/N=3). The performances of AuPt nanochains were superior to
those of individual Pt and Au nanoparticles. It is ascribed to the specific
hierarchical structures and synergistic effects of the bimetals.
PMID- 28415422
TI - Synthesis and characterization of redox-sensitive heparin-beta-sitosterol
micelles: Their application as carriers for the pharmaceutical agent,
doxorubicin, and investigation of their antimetastatic activities in vitro.
AB - Although there are several clinical attempts to treat tumors at the primary site,
only few therapies can inhibit the spread of metastatic cancers. In this study,
we synthesized redox-sensitive heparin-beta-sitosterol micelles that show
antimetastatic activity. Proton nuclear magnetic resonance and Fourier transform
infrared analyses confirmed the formation of bioreducible heparin-beta-sitosterol
(bHSC) conjugates, whereas dynamic light scattering was used to measure the
particle size and zeta potential. Both 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and flow cytometry assays confirmed the low toxicity
of the synthesized micelles. Doxorubicin (Dox) was encapsulated via the dialysis
method, and its loading and encapsulation efficiencies were 16.49+/-1.2% and
58.47+/-1.87%, respectively. An in vitro release study showed that approximately
89% and 52% of Dox were released after 48h in the presence and absence of reduced
glutathione, respectively. The hemocompatibility and antimetastatic effects of
bHSC were evaluated using the hemolysis and scratch assays, respectively. F-Actin
fluorescence microscopy showed that heparin- and bHSC-treated HeLa cells had
poorly oriented stress fibers. In summary, the synthesized bHSC micelles are good
candidates as drug delivery systems owing to their low toxicity, excellent
hemocompatibility, and antimetastatic effects.
PMID- 28415423
TI - Investigation of antifouling and disinfection potential of chitosan coated iron
oxide-PAN hollow fiber membrane using Gram-positive and Gram-negative bacteria.
AB - Chitosan coated iron oxide nanoparticles were impregnated into polyacrylonitrile
based hollow fiber membrane. The molecular weight cut off was varied in the range
of 120 to 145kDa with the concentration of nanoparticles. Incorporation of
nanoparticles improved the permeability, mechanical property and hydrophilicity
of the membrane. The contact angle of the membrane decreased from 80 degrees to
51 degrees and the permeability increased by 31% at 0.5wt% nanoparticles
concentration. The antibacterial and antifouling property of the membrane were
investigated with two biofilm causing Gram positive and Gram negative bacteria.
The damage of cell membrane was directly confirmed by release of cellular
constituent absorbing in 260nm. The cellular deformation on the membrane surface
was evident by direct microscopic observation in FESEM. This damage was likely
caused by electrostatic interaction between NH3+ group of nanoparticles and
anionic components of phosphoryl group of bacteria. The hollow fiber membrane
shows promising antibiofouling property even after long experimental run as
evident by 95% flux recovery ratio. The effect of operating conditions on
rejection and flux profile was investigated during long experimental run. The
result indicated that there was no detectable iron in the permeate sample that
could impose adverse health hazard.
PMID- 28415424
TI - Development of strong, biodegradable and highly elastomeric polycitrate-gelatin
hybrid polymer with enhanced cellular biocompatibility.
AB - Native human tissues possess incomparable biological performance due to their
strong and viscoelastic mechanical properties, and biocompatible compositions.
Herein, by a thermal polymerization and solvent hybridization method, we develop
biomimetic polycitrate-gelatin hybrid polymers (PC-GT) with strong mechanical
properties and tailored elastomeric behavior for tissue regeneration
applications. The incorporation of gelatin significantly enhanced the mechanical
properties and cellular biocompatibility of PC. PC-GT hybrids demonstrated the
135 times (from 7.5 to 1015MPa) and 11 times (from 4 to 46MPa) improvement for
the elastomeric modulus and tensile strength respectively as compared with PC
elastomers, while showing controlled stretchable and elastomeric behavior. In
addition, PC-GT hybrids significantly improved the fibroblasts (L929) attachment
and proliferation, suggesting their high biocompatibility. This study may provide
a novel strategy to design biocompatible hybrid polymers with strong and
elastomeric behavior for tissue regeneration and stretchable electronic devices
applications.
PMID- 28415425
TI - "Click" access to multilayer functionalized Au surface: A terpyridine patterning
example.
AB - This work is focused on self-assembled monolayers (SAMs) fabrication, using two
types of Au surfaces, by subsequent attachment of different layers in order to
develop a stable platform consisting of covalent multilayer functionalized gold
surfaces. The key step in the construction of SAMs is the covalent linkage to the
gold surface, via an amino-thiol derivative, of a cyclooctyne unit exhibiting
strained triple bonds which react fast (catalysts are not needed) and
quantitatively with organic azides and enable the introduction of various
chemical functionalized entities on the gold surface. The versatility of the
system is demonstrated by the reaction of the cyclooctyne decorated gold surface
with an azide functionalized terpyridine followed by step by step complexation
with Fe(II) and another terpyridine unit resulting into a multilayer covered gold
surface. The Au surfaces were characterized by XPS to determine the chemical
composition of the resulting SAMs. SPR was applied for real-time monitoring of
the molecular interactions that occurred on the Au surface for each deposited
layer. DPN was used to direct pattern the terpyridine-ink on a pre-functionalized
AuIDE electrode. The AFM topology resulted from DPN and PEIS demonstrated metal
coordinating ligand of Fe(II)-Terpy.
PMID- 28415426
TI - Influence of Dy in solid solution on the degradation behavior of binary Mg-Dy
alloys in cell culture medium.
AB - Rare earth element Dy is one of the promising alloying elements for magnesium
alloy as biodegradable implants. To understand the effect of Dy in solid solution
on the degradation of Mg-Dy alloys in simulated physiological conditions, the
present work studied the microstructure and degradation behavior of Mg-Dy alloys
in cell culture medium. It is found the corrosion resistance enhances with the
increase of Dy content in solid solution in Mg. This can be attributed to the
formation of a relatively more corrosion resistant Dy-enriched film which
decreases the anodic dissolution of Mg.
PMID- 28415428
TI - The effect of sliding onto the metal-electrolyte interface: Studying model
parameter modifications by means of EIS.
AB - Several problems are associated with corrosion-wear occurring on metal-on-metal
hip implants made out of cobalt-chromium based alloys. Low temperature
carburizing, a process that creates a hard and corrosion resistant diffused layer
in Cobalt-Chromium-Molybdenum (CoCrMo) alloys, known as S-phase, may be a
possible solution towards mitigating these problems. In this work, static- and
tribo-corrosion testing involving an alumina versus CoCrMo (untreated and
carburized) were conducted in Ringer's solution. Electrochemical impedance
spectroscopy was used to compare impedance plots attained before and after
sliding so as to understand how the metal-electrolyte interface is affected by
rubbing. Both untreated and carburized CoCrMo experienced extensive reduction in
corrosion resistance following sliding wear damage such that one should expect a
considerably deteriorated performance of both surfaces in a tribocorrosion
application. The structure of the interface was relatively unaffected after
sliding at the equilibrium and passive potentials. This implies that the layers
making up the interface before sliding were still present after sliding. However,
their properties changed - the interface's real resistance dropped while its
capacitance increased. The former was linked to a weaker, damaged passive film
while the latter was linked to accumulation of wear debris and corrosion
products.
PMID- 28415427
TI - Surface physical chemistry properties in coated bacterial cellulose membranes
with calcium phosphate.
AB - Bacterial cellulose has become established as a new biomaterial, and it can be
used for medical applications. In addition, it has called attention due to the
increasing interest in tissue engineering materials for wound care. In this work,
the bacterial cellulose fermentation process was modified by the addition of
chondroitin sulfate to the culture medium before the inoculation of the bacteria.
The biomimetic process with heterogeneous calcium phosphate precipitation of
biological interest was studied for the guided regeneration purposes on bacterial
cellulose. FTIR results showed the incorporation of the chondroitin sulfate in
the bacterial cellulose, SEM images confirmed the deposition of the calcium
phosphate on the bacterial cellulose surface, XPS analysis showed a selective
chemical group influences which change calcium phosphate deposition, besides, the
calcium phosphate phase with different Ca/P ratios on bacterial cellulose surface
influences wettability. XTT results concluded that these materials did not affect
significantly in the cell viability, being non-cytotoxic. Thus, it was produced
one biomaterial with the surface charge changes for calcium phosphate deposition,
besides different wettability which builds new membranes for Guided Tissue
Regeneration.
PMID- 28415429
TI - Aminated carbon-based "cargo vehicles" for improved delivery of methotrexate to
breast cancer cells.
AB - The purpose of study was to conjugate and evaluate methotrexate with C60
fullerenes and multi-walled carbon nanotubes (MWCNTs) for better drug delivery to
cancer cells, and also to compare these two systems. C60-fullerenes and MWCNTs
were functionalized by 1,3-dipolar cycloaddition using glycine and
paraformaldehyde. Methotrexate (MTX) was esterified and conjugated to the
functionalized carbon-based carriers. The conjugates were characterized for
micromeritics and drug conjugation. The systems were evaluated for drug release
in various pH, MTT cytotoxicity assay, protein binding, cellular uptake,
haemolytic profile and pharmacokinetics. Spectroscopic studies confirmed the
successful conjugation of drug to the aminated carbon-based carriers. The
developed systems released more drug at the pH of cancer cells to that of the pH
of plasma. The carriers were compatible with erythrocytes and offered substantial
cytotoxicity. Better cellular uptake was confirmed by confocal laser scanning
microscopy. C60-fullerenes/MWCNTs modulated the pharmacokinetic profile of drug
in desired manner, resulting in better retention and compartment availability.
However, the results from C60-fullerenes were observed to be better than that
from MWCNTs. The present findings established the potential of carbon-based
aminated nanocarriers for delivery of methotrexate in safer and effective manner.
PMID- 28415430
TI - X-ray visible and doxorubicin-loaded beads based on inherently radiopaque
poly(lactic acid)-polyurethane for chemoembolization therapy.
AB - The aim of current study was to develop drug-loaded polymeric beads with
intrinsic X-ray visibility as embolic agents, targeting for noninvasive
intraoperative location and postoperative examination during chemoembolization
therapy. To endow polymer with inherent radiopacity, 4,4'-isopropylidinedi-(2,6
diiodophenol) (IBPA) was firstly synthesized and employed as a contrast agent,
and then a set of radiopaque iodinated poly(lactic acid)-polyurethanes (I-PLAUs)
via chain extender method were synthesized and characterized. These I-PLAU
copolymers possessed sufficient radiopacity, in vitro non-cytotoxicity with human
adipose-derived stem cells, and in vivo biocompatibility and degradability in
rabbit model via intramuscular implantation. Doxorubicin (DOX), as a
chemotherapeutic agent, was further incorporated into I-PLAU beads via a double
emulsification (W/O/W) method. For drug release, two ratios of DOX-loaded I-PLAU
beads exhibited calibrated size (200-550MUm), porous internal structure, good X
ray visibility, evenly drug loading as well as tunable drug release. A
preliminary test on in vitro tumor cell toxicity demonstrated that the DOX-loaded
I-PLAU beads performed efficient anti-tumor effect. This study highlights novel X
ray visible drug-loaded I-PLAU beads used as promising embolic agents for non
invasive in situ X-ray tracking and efficient chemotherapy, which could bring
opportunities to the next generation of multifunctional embolic agents.
PMID- 28415431
TI - In vitro cytotoxicity study of dual drug loaded chitosan/palladium nanocomposite
towards HT-29 cancer cells.
AB - Conjugated drug delivery has gained immense interest due to the possibility of
overcoming the resistance of cancer cells to a specific drug when treated using
it for a period of time. In the present study, CS/Pd nanocomposite has been
prepared using cost effective chemical reduction method and has been used for the
delivery of curcumin (CUR) and 5-Fluorouracil (5-FU) separately and in a
conjugated form. The prepared nanocomposite before and after drug encapsulation
have been studied using various characterization techniques. The release of drugs
from the nanocomposite with respect to time has been analyzed and the release
kinetics has also been studied. The release profile is mostly seen to adhere to
zero order kinetics which represents the constant release of drugs from drug
delivery system. This is the most favored release kinetic as this leads to the
prolonged release of the drug, thus leading to a reduction in the number of doses
administered. The cytotoxicity of the drug loaded nanocomposites on colon cancer
cells has been studied, which shows the effectiveness of the composite system
towards successfully inhibiting the growth of cancer cells.
PMID- 28415432
TI - Fabrication of dicalcium phosphate dihydrate-coated beta-TCP granules and
evaluation of their osteoconductivity using experimental rats.
AB - beta-Tricalcium phosphate (beta-TCP) has attracted much attention as an
artificial bone substitute owing to its biocompatibility and osteoconductivity.
In this study, osteoconductivity of beta-TCP bone substitute was enhanced without
using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is
known to possess the highest solubility among calcium phosphates, was coated on
beta-TCP granules by exposing their surface with acidic calcium phosphate
solution. The amount of coated DCPD was regulated by changing the reaction time
between beta-TCP granules and acidic calcium phosphate solution. Histomorphometry
analysis obtained from histological results revealed that the approximately
10mol% DCPD-coated beta-TCP granules showed the largest new bone formation
compared to DCPD-free beta-TCP granules, approximately 2.5mol% DCPD-coated beta
TCP granules, or approximately 27mol% DCPD-coated beta-TCP granules after 2 and
4weeks of implantation. Based on this finding, we demonstrate that the
osteoconductivity of beta-TCP granules could be improved by coating their surface
with an appropriate amount of DCPD.
PMID- 28415433
TI - Multifunctional nanospheres for co-delivery of methotrexate and mild hyperthermia
to colon cancer cells.
AB - A multifunctional nanomedicine platform was designed and evaluated for efficient
colon cancer therapy by a combinatorial therapeutic approach based on a
chemotherapeutic drug and mild hyperthermia. Advantage was taken from the dual
role of methotrexate (MTX), as folate receptor-targeting, overexpressed in tumor
cells, and as anticancer drug. Incorporation of superparamagnetic iron oxide
nanoparticles (SPIONs) allows to heat cancer cells externally through an
alternating magnetic field. The developed nanocarrier was based on polyethylene
glycol-polylactic acid (PEG-PLA) nanospheres to improve biocompatibility,
enhancing their targeting by prolonging blood circulation time. By an emulsion
evaporation method the nanospheres were produced and then characterized for size
distribution, zeta-potential, in vitro drug release profile and cellular studies.
The co-delivery of MTX and SPIONs on PEG-PLA nanospheres resulted in nanocarriers
with a size of 160nm in diameter, a polydispersity index below 0.2 and a zeta
potential of ca. -18mV. Multifunctional nanospheres were monodisperse and stable
up to 3months. MTX was released preferentially under mild hyperthermia
conditions. The multifunctional nanospheres were able to increase the
cytotoxicity of MTX towards Caco-2 and SW-480 colon cancer cells, in comparison
to free drug. Also, the nanospheres allowed the incorporated MTX to induce
greater cell cycle arrest and apoptotic effects than the free MTX. This study
provides evidences that MTX-SPIONs-PEG-PLA nanospheres are a promising solution
to address colorectal cancer over-expressing folate receptors, by a combinatory
approach.
PMID- 28415434
TI - Design and development of a hybrid bioartificial water-induced shape memory
polymeric material as an integral component for the anastomosis of human hollow
organs.
AB - A large number of pathologies require the resection of the bowel and anastomoses
to rejoin the two remaining stumps to regain lumen patency. Various materials
have been used to rejoin one bowel end to the other such as catgut, stainless
steel, and absorbable sutures. The present method for anastomosis surgery uses an
entero-entero anastomosis (EEA) circular stapler with only a staple line. This
method can have some drawbacks, such as intracellular fluid leakage and local
inflammations. The aim of this study is to design and develop a novel
bioartificial polymer with a ring shape made of polyvinyl alcohol (PVA) and
gelatin (80/20 ratio (w/w)) loaded both directly with acetylsalicylic acid and
with nanoparticles incorporating the same drug to reduce local inflammation even
for a prolonged period of time. A physical method (8cycles freezing/thawing) was
used to obtain a crosslinked bioartificial shape memory ring. Mechanical analysis
showed a storage modulus having a comparable value with that of the human colon.
HPLC analysis pointed out a sustained and prolonged release of the anti
inflammatory drug both immediately after anastomosis surgery and during healing
period. Cell culture tests indicated the cytocompatibility of the bioartificial
device. A shape memory of the hydrogel prepared in ring form was observed at 37
degrees C after immersion in water. These bioartificial devices can represent a
new approach to serve as a multifunctional anastomotic ring.
PMID- 28415435
TI - Developing an electrochemical sensor based on a carbon paste electrode modified
with nano-composite of reduced graphene oxide and CuFe2O4 nanoparticles for
determination of hydrogen peroxide.
AB - In this paper, a highly sensitive voltammetric sensor based on a carbon paste
electrode with CuFe2O4 nanoparticle (RGO/CuFe2O4/CPE) was designed for
determination of hydrogen peroxide (H2O2). The electrocatalytic reduction of H2O2
was examined using various techniques such as cyclic voltammetry (CV),
chronoamperometry, amperometry and differential pulse voltammetry (DPV). CuFe2O4
nanoparticles were synthesized by co-precipitation method and characterized with
scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X-ray
diffraction (XRD), and Fourier transform infrared (FTIR) techniques. Then, a high
conductive platform based on a carbon paste electrode modified with RGO and
CuFe2O4 nanoparticles was prepared as a suitable platform for determination of
hydrogen peroxide. Under the optimum conditions (pH5), the modified electrode
indicated a fast amperometric response of <2s, good linear range of 2 to 200MUM,
low detection limit of 0.52MUM for determination of hydrogen peroxide. Also, the
peak current of differential pulse voltammetry (DPV) of hydrogen peroxide is
increased linearly with its concentration in the ranges of 2 to 10MUM and 10 to
1000MUM. The obtained detection limit for hydrogen peroxide was evaluated to be
0.064MUM by DPV. The designed sensor was successfully applied for the assay of
hydrogen peroxide in biological and pharmaceutical samples such as milk, green
tea, and hair dye cream and mouthwash solution.
PMID- 28415436
TI - A novel composite hydrogel initiated by Spinacia oleracea L. extract on Hela
cells for localized photodynamic therapy.
AB - In this study, the poly (ethylene glycol) double acrylates (PEGDA) was first
initiated by Spinacia oleracea L. extract (SOLE) to in situ form a polymer
hydrogel shell on Hela cells with near infra-red irradiation. The SOLE was also a
natural photosensitizer for photodynamic therapy of tumor. The use of SOLE is
simple, eco-friendly, low cost, and convenient. More importantly, the PEGDA/SOLE
composite hydrogel shell on Hela cells not merely prevents SOLE from diffusing to
normal tissue for reducing the side effects, but also keeps high SOLE
concentration on tumor cell for improving the antitumor effect. Such a hydrogel
system has good biocompatibility and exhibits high therapeutic efficacy. This
study extended the application of the SOLE/PEGDA gel in photodynamic therapy.
PMID- 28415437
TI - A simplistic approach to green future with eco-friendly luminescent carbon dots
and their application to fluorescent nano-sensor 'turn-off' probe for selective
sensing of copper ions.
AB - Zero-dimensional fluorescent nanoparticles having specificity as molecular probe
appears to be strategically balanced fluorescent nano-probes. In this work,
purified lemon extract and l-arginine have been thermally coupled for the
extremely acute detection of Cu2+ in aqueous medium. The Cu2+ ions may be
captured by the amino groups on the surface of the nano-sensor to form cupric
ammine complex resulting in quenched fluorescence via an inner filter effect. Our
proposed nano-probe is N-doped carbon dots (NCDs) which are efficiently selective
as fluorescent chemosensor due to enormous binding affinity towards Cu2+ in a
wide range of concentration (0.05-300MUM) within a few minutes.
PMID- 28415438
TI - Development of high efficacy peptide coated iron oxide nanoparticles encapsulated
amphotericin B drug delivery system against visceral leishmaniasis.
AB - Visceral leishmaniasis, a protozoan disease transmitted by phlebotomine sandflies
which affect mostly in Indian sub-continent. The treatment for visceral
leishmaniasis (VL) caused by Leishmania donovani are limited and unsatisfactory.
Currently available drug against such as miltefosine and polymer based drugs
amBisome has high efficacy against VL but found serious side effects and poor
absorbance. To overcome this, we developed peptide (glycine) coated iron oxide
(Fe3O4) nanoparticles (GINPs) encapsulated amphoterecin B (AmB) drug against
visceral leishmaniasis. Synthesis of GINPs was carried out and different
characterization technique used to confirm the synthesis and size of GINPs GINPs
AmB showed that particle size in the range of 10-15nm and closed to spherical in
shaped. GINPs-AmB showed release rate of AmB is higher at lower pH. Significantly
two fold higher efficacies of GINP encapsulated AmB during in vitro study. There
was a substantial reduction in the total parasite burden in spleen in treated
groups (GINPs encapsulate AmB), compare to AmB alone. The results obtained from
this study revealed that AmB loaded GINPs is twofold effective than AmB and
therefore, it opens a new avenue for use of AmB loaded GINPs against VL.
PMID- 28415439
TI - Novel synthesis and structural analysis of zinc oxide nanoparticles for the non
enzymatic glucose biosensor.
AB - A non-enzymatic glucose biosensor was developed by utilizing the zinc oxide
nanoparticles (ZnO NPs) synthesized by a novel green method using the leaf
extract of Ocimum tenuiflorum. The structural, optical and morphological
properties of ZnO NPs characterized by means of X-ray diffraction (XRD),
ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FTIR)
spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDAX)
spectroscopy, and transmission electron microscopy (TEM). The XRD analysis
revealed that the ZnO NPs were crystalline and had a hexagonal wurtzite
structure. The crystallite size measured by XRD was the same as that measured
using SEM and TEM. The UV-vis absorption spectrum estimates the band gap of ZnO
NPs present in the range of 2.82 to 3.45eV. The reduction and formation of ZnO
NPs mainly due to the involvement of leaf extract bio-molecular compounds
analyzed from the FTIR spectra. The SEM result confirms the morphology of the NPs
responsible from the various concentration of leaf extract in the synthesis
process. HRTEM analysis depicts the spherical structure of ZnO NPs. The
synthesized NPs have the average size ranges from 10 to 20nm. The fabricated
GCE/ZnO glucose sensor represents superior electro catalytic activity that has
been observed for ZnO NPs with a reproducible sensitivity of 631.30MUAmM-1cm-2,
correlation coefficient of R=0.998, linear dynamic range from 1-8.6mM, low
detection limit of 0.043MUM (S/N=3) and response time<4s.
PMID- 28415440
TI - Template electrodeposition of high-performance copper oxide nanosensors for
electrochemical analysis of hydrogen peroxide.
AB - We report on the facile electrodeposition of copper nanostructures on graphite
lead substrate using anionic, cationic and non-ionic surfactant templates.
Physical and electrochemical characterisation confirmed the influence of
templates on the morphology and electrochemical catalytic activities of the
copper electrodeposits. These electrodes were shown to be excellent
electrocatalyst for the fast detection of hydrogen peroxide. A maximum
sensitivity of 951.45MUA/mM/cm2, LOD of 0.43MUM, response time of <1s and a
linearity in wide range of concentration from 1MUM to 5mM were observed when
sodium dodecyl sulfate was used as the template. While most of the previously
reported sensors have advantages either on the facile synthesis or fast detection
of analyte, our methodology enables preparation of the electrode within 120s and
analysis within another 60s without any complicated procedure, thereby
demonstrating one of the fastest and cost-effective method for hydrogen peroxide
analysis with high sensitivity and selectivity.
PMID- 28415441
TI - Stress stiffened silicon nitride micro bridges array as substrate with tunable
stiffness for cell culture.
AB - Recently, interactions between one-dimensional structural stiffness of physical
micro environments and cell biological process have been widely studied. However
in previous studies, the influence of structural stiffness on biological process
was coupled with the influence of micro fiber curvature. Therefore decoupling the
influences of fiber curvature and structural stiffness on cell biological process
is of prime importance. In this study, we proposed a novel cell culture substrate
comprised of silicon nitride bridges whose structure stiffness can be regulated
by altering the axial residual stress without changing material and geometry
properties. Both theoretical calculations and finite element simulations were
performed to study the influence of residual stress on structure stiffness of
bridges. Then multi-positions AFM bending tests were implemented to measure local
stiffness of a single micro bridge so as to verify our predictions. NIH/3T3 mouse
fibroblast cells were cultured on our substrates to examine the feasibility of
the substrate application for investigating cellular response to microenvironment
with variable stiffness. The results showed that cells on the edge region near
bridge ends were more spread, elongated and better aligned along the bridge axial
direction than those on the bridge center region. The results suggest that cells
can sense and respond to the differences of stiffness and stiffness gradient
between the edge and the center region of the bridges, which makes this kind of
substrates can be applied in some biomedical fields, such as cell migration and
wound healing.
PMID- 28415442
TI - Small intestinal submucosa: A potential osteoconductive and osteoinductive
biomaterial for bone tissue engineering.
AB - SIS is an acellular, naturally occurring collagenous extracellular matrix (ECM)
material with various bioactive factors, which broadly applied in tissue
engineering in clinic. Several studies have applied SIS in bone tissue
engineering to enhance bone regeneration in animal models. However, the mechanism
was rarely investigated. The aim of the current study was to investigate the
osteoconductivity and osteoinductivity of SIS scaffold to bone regeneration
systematically and the potential mechanism. Our results showed that SIS scaffold
with excellent biocompatibility was beneficial for cell attachment,
proliferation, migration and osteogenic differentiation of various cells
contributing to bone repair. In mouse calvarial defect model, bone regeneration
was significantly enhanced in the defects implanted with SIS scaffolds, along
with the up-regulation of BMP-2 and CD31 expression. Accordingly, ID-1, the
downstream target gene of BMPs, was increased in BMSCs cultured on SIS scaffolds.
The results of this study suggest that SIS scaffold is a potential
osteoconductive and osteoinductive biomaterial which plays multiple roles to
various cells during process of bone regeneration.
PMID- 28415443
TI - 3-month parenteral PLGA microsphere formulations of risperidone: Fabrication,
characterization and neuropharmacological assessments.
AB - The study aims at formulation and characterization of three months parenteral
risperidone loaded polymeric microspheres (p-RLPMs) as a sustained delivery
system and established their in vitro and in vivo assessments. The p-RLPMs
formulations were prepared by solvent extraction and diffusion method. The
optimized p-RLPMs (batch RPLGA-1) formulation demonstrated favorable different
physicochemical properties such as mean particle size (104+/-5.34MUm), percent
porosity (44.56+/-3.11%) and percent drug loading (38.42+/-2.67%). The physical
state characterization, Fourier transformed infrared spectroscopy analysis showed
no changes in the chemical structure of risperidone (RPD) in the batch RPLGA-1
formulation and differential scanning calorimetry study confirmed, pure RPD
retained its crystallinity in the batch RPLGA-1 formulation. The SEM micrographs
of the all p-RLPMs formulations revealed the irregular shapes and indentations.
The GC/MS results showed that the residual organic solvent content in the batch
RPLGA-1 formulation was below the limits. Pharmacokinetic parameters revealed
that optimized RPLGA-1 formulation exhibited an initial burst followed by an
excellent sustained release as compared to pure RPD as well as other
formulations. Furthermore, in vivo studies of the batch, RPLGA-1 formulation
showed an antipsychotic effect that was significantly prolonged over that of pure
RPD solution for up to 72h with fewer extrapyramidal side effects. Thus, results
of this study prove the suitability of using poly(lactic-co-glycolic acid)
copolymer to develop sustained release p-RLPMs formulations that can tailor in
vivo behavior and enhance the pharmacological effectiveness of the RPD.
PMID- 28415444
TI - Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation,
biocompatibility studies and its antimicrobial activity against periodontal
pathogens.
AB - The present work aims to investigate the efficacy of thermoreversible gel of
cranberry juice concentrate (CJC) as local drug delivery for the treatment of
periodontitis. CJC was initially tested for its antimicrobial activities like
MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of
organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P.
gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal
infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC
value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity
(70-85%). CJC was evaluated for its biocompatibility using periodontal
fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on
periodontopathogen PG derived virulence factors (fimA and kgp) was studied using
real time polymerase chain reaction (RT-PCR) technique wherein down regulation of
selected genes demonstrated inhibitory effect against PG virulence factors.
Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as
thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated
for its gelation temperature, viscosity, gel strength and mucoadhesive strength.
Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially
available chlorhexidine gluconate gel (0.2%) using agar well diffusion
demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the
formulated thermoreversible gel of CJC could serve as a novel herbal alternative
to currently available periodontal treatment modalities.
PMID- 28415445
TI - Microstructural and surface modifications and hydroxyapatite coating of Ti-6Al-4V
triply periodic minimal surface lattices fabricated by selective laser melting.
AB - Ti-6Al-4V Gyroid triply periodic minimal surface (TPMS) lattices were
manufactured by selective laser melting (SLM). The as-built Ti-6Al-4V lattices
exhibit an out-of-equilibrium microstructure with very fine alpha' martensitic
laths. When subjected to the heat treatment of 1050 degrees C for 4h followed by
furnace cooling, the lattices show a homogenous and equilibrium lamellar
alpha+beta microstructure with less dislocation and crystallographic defects
compared with the as-built alpha' martensite. The as-built lattices present very
rough strut surfaces bonded with plenty of partially melted metal particles. The
sand blasting nearly removed all the bonded metal particles, but created many
tiny cracks. The HCl etching eliminated these tiny cracks, and subsequent NaOH
etching resulted in many small and shallow micro-pits and develops a sodium
titanate hydrogel layer on the surfaces of the lattices. When soaked in simulated
body fluid (SBF), the Ti-6Al-4V TPMS lattices were covered with a compact and
homogeneous biomimetic hydroxyapatite (HA) layer. This work proposes a new method
for making Ti-6Al-4V TPMS lattices with a homogenous and equilibrium
microstructure and biomimetic HA coating, which show both tough and bioactive
characteristics and can be promising materials usable as bone substitutes.
PMID- 28415446
TI - Corrigendum to "Graphene oxide as a nanocarrier for controlled release and
targeted delivery of an anticancer active agent, chlorogenic acid" [J. Mater.
Sci. Eng. C 74(2017) 177-185].
PMID- 28415447
TI - Corrigendum to "Poly-dopamine-beta-cyclodextrin: A novel nanobiopolymer towards
sensing of amino acids at physiological pH" [Materials Science and Engineering: C
Volume 69, 1 December 2016, Pages 343-357].
PMID- 28415448
TI - Corrigendum to "Preparation and characterization of PEGylated multiwall carbon
nanotubes as covalently conjugated and non-covalent drug carrier: A comparative
study" [Mater. Sci. Eng. C 74 (2017)1-9].
PMID- 28415449
TI - Complementary approaches for the evaluation of biocompatibility of 90Y-labeled
superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles.
AB - Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and
therapeutic applications in medicine. Design and development of new iron oxide
based MNPs for such applications is of rather limited breadth without reliable
and sensitive methods to determine their levels in body tissues. Commonly used
methods, such as ICP, are quite problematic, due to the inability to decipher the
origin of the detected iron, i.e. whether it originates from the MNPs or
endogenous from tissues and bodily fluids. One of the approaches to overcome this
problem and to increase reliability of tracing MNPs is to partially substitute
iron ions in the MNPs with Er. Here, we report on the development of citric acid
coated (Fe,Er)3O4 nanoparticles and characterization of their physico-chemical
and biological properties by utilization of various complementary approaches. The
synthesized MNPs had a narrow (6-7nm) size distribution, as consistently seen in
atomic pair distribution function, transmission electron microscopy, and DC
magnetization measurements. The particles were found to be superparamagnetic,
with a pronounced maximum in measured zero-field cooled magnetization at around
90K. Reduction in saturation magnetization due to incorporation of 1.7% Er3+ into
the Fe3O4 matrix was clearly observed. From the biological standpoint, citric
acid coated (Fe,Er)3O4 NPs were found to induce low toxicity both in human cell
fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of
the MNPs after intravenous administration in healthy Wistar rats was followed by
the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found
in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID).
Quantitative agreement with these observations was obtained by ICP-MS elemental
analysis using Er as the detected tracer. Based on the favorable physical,
chemical and biological characteristics, citric acid coated (Fe,Er)3O4 MNPs could
be further considered for the potential application as a diagnostic and/or
therapeutic agent. This work also demonstrates that combined application of these
techniques is a promising tool for studies of pharmacokinetics of the new MNPs in
complex biological systems.
PMID- 28415450
TI - Impact of silica nanoparticle surface chemistry on protein corona formation and
consequential interactions with biological cells.
AB - Nanoparticles (NP) physico-chemical features greatly influence NP/cell
interactions. NP surface functionalization is often used to improve NP
biocompatibility or to enhance cellular uptake. But in biological media, the
formation of a protein corona adds a level of complexity. The aim of this study
was to investigate in vitro the influence of NP surface functionalization on
their cellular uptake and the biological response induced. 50nm fluorescent
silica NP were functionalized either with amine or carboxylic groups, in presence
or in absence of polyethylene glycol (PEG). NP were incubated with macrophages,
cellular uptake and cellular response were assessed in terms of cytotoxicity, pro
inflammatory response and oxidative stress. The NP protein corona was also
characterized by protein mass spectroscopy. Results showed that NP uptake was
enhanced in absence of PEG, while NP adsorption at the cell membrane was fostered
by an initial positively charged NP surface. NP toxicity was not correlated with
NP uptake. NP surface functionalization also influenced the formation of the
protein corona as the profile of protein binding differed among the NP types.
PMID- 28415451
TI - The sustained delivery of temozolomide from electrospun PCL-Diol-b-PU/gold
nanocompsite nanofibers to treat glioblastoma tumors.
AB - In the present study, the PCL-Diol-b-PU/Au nanocompsite nanofibers were
fabricated via electrospinning process during two different stages to load an
anticancer temozolomide (TMZ) drug into the nanofibers. The first stage was the
incorporation of Au nanoparticles into the nanofibers and the second stage was
coating the gold nanoparticles on the surface of PCL-Diol-b-PU/Au composite
nanofibers. The prepared nanofibrous formulations were characterized using FTIR,
SEM and TEM analysis. Box-Behnken-design was used to investigate the influence of
electrospinning parameters including solution concentration, applied voltage to
tip-collector distance ratio and collector speed on the morphology and fiber
diameter of PCL-Diol-b-PU/Au nanofibers. Drug loading efficiency, in vitro
release profiles of TMZ from PCL-Diol-b-PU/Au and gold-coated PCL-Diol-b-PU/Au
composite nanofibers as well as in vitro antitumor efficacy against U-87 MG human
glioblastoma cells were carried out. The TMZ release data were well described
using Korsmayer-Peppas kinetic model in which results indicated Fickian diffusion
of TMZ from nanofibers. The obtained results revealed the higher efficiency of
PCL-Diol-b-PU/Au@TMZ nanofibrous implants for treatment of glioblastoma tumors.
PMID- 28415452
TI - An ultra-sensitive Au nanoparticles functionalized DNA biosensor for
electrochemical sensing of mercury ions.
AB - The present work describes an effective strategy to fabricate a highly sensitive
and selective DNA-biosensor for the determination of mercury ions (Hg2+). The DNA
1 was modified onto the surface of Au electrode by the interaction between
sulfydryl group and Au electrode. DNA probe is complementary with DNA 1. In the
presence of Hg2+, the electrochemical signal increases owing to that Hg2+
mediated thymine bases induce the conformation of DNA probe to change from line
to hairpin and less DNA probes adsorb into DNA 1. Taking advantage of its
reduction property, methylene blue is considered as the signal indicating
molecule. For improving the sensitivity of the biosensor, Au nanoparticles (Au
NPs) modified reporter DNA 3 is used to adsorb DNA 1. Electrochemical behaviors
of the biosensor were evaluated by electrochemical impedance spectroscopy and
cyclic voltammetry. Several important parameters which could affect the property
of the biosensor were studied and optimized. Under the optimal conditions, the
biosensor exhibits wide linear range, high sensitivity and low detection limit.
Besides, it displays superior selectivity and excellent stability. The biosensor
was also applied for water sample detection with satisfactory result. The novel
strategy of fabricating biosensor provides a potential platform for fabricating a
variety of metal ions biosensors.
PMID- 28415453
TI - Role of generation on folic acid-modified poly(amidoamine) dendrimers for
targeted delivery of baicalin to cancer cells.
AB - Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has
limited water solubility, non-specific tumor targeting, and low bioavailability,
which severely limited its clinical application. The aim of this study was to
develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers
(PAMAM-FA) as carrier systems for improvement of water solubility and tumor
specificity of BAI, and study the role of generation on the physiochemical
properties and biological effects of PAMAM-FA/BAI complexes. In this work, four
generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3
FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm,
258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI
complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment
efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%,
respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The
formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS
(pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased
drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR
negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely
related with the generation of PAMAM. The MTT assay results showed that PAMAM
FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA
modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition
efficiency. The cell cycle and cell apoptosis analysis further demonstrated the
tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that
the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to
enhance its anti-tumor efficacy.
PMID- 28415454
TI - Development of a DNA-liposome complex for gene delivery applications.
AB - The association structures formed by cationic liposomes and DNA (Deoxyribonucleic
acid)-liposome have been effectively utilized as gene carriers in transfection
assays. In this research study, cationic liposomes were prepared using a modified
lipid film hydration method consisting of a lyophilization step for gene delivery
applications. The obtained results demonstrated that the mean particle size had
no significant change while the polydispersity (PDI) increased after
lyophilization. The mean particle size slightly reduced after lyophilization
(520+/-12nm to 464+/-25nm) while the PDI increased after lyophilization (0.094+/
0.017 to 0.220+/-0.004). In addition. The mean particle size of vesicles
increases when DNA is incorporated to the liposomes (673+/-27nm). According to
the Scanning Electron Microscopy (SEM) and transmission electron microscopy (TEM)
images, the spherical shape of liposomes confirmed their successful preservation
and reconstitution from the powder. It was found that liposomal formulation has
enhanced transfection considerably compared to the naked DNA as negative control.
Finally, liposomal formulation in this research had a better function than
Lipofectamine(r) 2000 as a commercialized product because the cellular activity
(cellular protein) was higher in the prepared lipoplex than Lipofectamine(r)
2000.
PMID- 28415455
TI - Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin
hydrochloride.
AB - A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated
via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system
for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor
therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability,
blood compatibility and biocompatibility confirmed by the hemolytic test and in
vitro cytotoxicity study. Its safety issue was greatly improved via Hep
modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and
dependent on pH value. The release rate of DOX from GO-ADH-Hep/DOX was pH
sensitive and much-slower than that of free DOX solution suggesting the sustained
drug-release capacity of this prepared nanocomplexes. In addition, the results of
cytotoxicity study illustrated that this fabricated nanocomplexes displayed
effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the
in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX
nanocomplexes could significantly prolong the retention time of DOX in vivo and
this was consistent with the in vitro drug release performance. And finally,
according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce
cardiotoxicity deriving from DOX solution and also decrease the pulmonary
toxicity deriving from unmodified GO. Based on the in vitro and in vivo
investigations, the fabricated GO-ADH-Hep could be a promising candidate as an
ideal nano-carrier for drug delivery and anti-cancer therapy.
PMID- 28415456
TI - Osteoinductive composite coatings for flexible intramedullary nails.
AB - This work presents composite coatings based on a copolymer of vinylidene fluoride
with tetrafluoroethylene (VDF-TeFE) and hydroxyapatite (HA) for flexible
intramedullary nails (FIN). The effect of the proportion of VDF-TeFE (100-25%
wt.) on physicochemical and biological properties of the composite coatings was
investigated. It was shown that a decrease of VDF-TeFE in the coating hinders its
crystallization in beta and gamma forms which have piezoelectric properties. The
decrease also reduces an adhesive strength to 9.9+/-2.4MPa and a relative
elongation to 5.9+/-1.2%, but results in increased osteogenesis. It was
demonstrated that the composite coatings with 35% VDF-TeFE has the required
combination of physicochemical properties and osteogenic activity. Comparative
studies of composite coatings (35% VDF-TeFE) and calcium phosphate coatings
produced using micro-arc oxidation, demonstrated comparable results for strength
of bonding of these FINs with trabecular bones (~530MPa). It was hypothesized
that the high osteoinductive properties of the composite coatings are due to
their piezoelectric properties.
PMID- 28415457
TI - A novel nano-hydroxyapatite - PMMA hybrid scaffolds adopted by conjugated thermal
induced phase separation (TIPS) and wet-chemical approach: Analysis of its
mechanical and biological properties.
AB - In this study, we report the preparation of nano-hydroxyapatite (nHAp)
incorporated poly(methyl methacrylate) (PMMA) scaffolds by conjugated thermal
induced phase separation (TIPS) and wet-chemical approach, which essentially
facilitates the enhancement of both mechanical as well as biological properties
of the scaffolds. The dissolution of PMMA was accomplished by acetone (Ace
scaffold), ethanol-water (E-W scaffold) and isopropanol-water (I-W scaffold)
mixtures as solvents. The existence of nHAp in PMMA matrix was investigated
systematically. The higher degree of porous architecture was achieved from Ace
scaffolds compared to both I-W and E-W scaffolds. On the other hand, the dense
porous architecture of the I-W scaffold exhibited superior hardness and
compressive strength than that of the Ace and E-W scaffolds. All the fabricated
samples demonstrated enhanced in vitro bioactivity with respect to increasing
immersion period as a result of flower-like in vitro apatite layer formation. The
MTT assay was carried out for 1day and 3day culture using Saos-2 osteoblast-like
cells, which showed better cell proliferation with increasing culture period
owing to the interconnected pore architecture of scaffolds and the rational
hemocompatibility as per the ASTM standard F756-00.
PMID- 28415458
TI - Nanopatterned polystyrene-b-poly(acrylic acid) surfaces to modulate cell-material
interaction.
AB - In this work we explore the effect of surface nanoarchitecture of polystyrene
(PS) and polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymer films on
cell viability. PS and PS-b-PAA have been nanopatterned at temperatures of 110,
120 and 140 degrees C using nanoporous aluminium oxide membranes (AAO) as a
template. Surface architecture strongly depends on the infiltration temperature
and the nature of the infiltrated polymer. High patterning temperatures yield
hollow fibre shape architecture at the nanoscale level, which substantially
modifies the surface hydrophobicity of the resulting materials. Up to date very
scarce reports could be found in the literature dealing with the interaction of
microstructured/nanostructured polymeric surfaces with cancer cells. Therefore,
MCF-7 breast cancer cells have been selected as a model to conduct cell viability
assays. The findings reveal that the fine-tuning of the surface nanoarchitecture
contributes to the modification of its biocompatibility. Overall, this study
highlights the potential of AAO membranes to obtain well-defined tailored
morphologies at nanoscale level and its importance to develop novel soft
functional surfaces to be used in the biomedical field.
PMID- 28415459
TI - The effect of hirudin modification of silk fibroin on cell growth and
antithrombogenicity.
AB - Thrombus formation remains a particular challenge for small-diameter vascular
grafts. In this study, the direct thrombin inhibitor hirudin (Hir) was used to
modify silk fibroin films in an attempt to enhance its antithrombogenic
properties. Hir was successfully attached to silk fibroin and uniformly
distributed in the regenerative material. Hir-modified films showed good
cytocompatibility, and supported adhesion and proliferation of fibroblasts
(L929), human umbilical vascular endothelial cells (HUVECs) and human aortic
smooth muscle cells (HASMCs). Proliferation of HAVSMCs was inhibited by
increasing Hir concentration. Activated partial thrombin time (APTT), prothrombin
time (PT) and thrombin time (TT) of Hir-modified silk fibroin tubular scaffolds
(SFTSs) were all increased markedly compared with fresh rabbit blood, ethanol
treated SFTS and unmodified SFTS, demonstrating the improved antithrombogenicity
of SFTSs following modification with Hir.
PMID- 28415460
TI - Poly arginine-graphene quantum dots as a biocompatible and non-toxic
nanocomposite: Layer-by-layer electrochemical preparation, characterization and
non-invasive malondialdehyde sensory application in exhaled breath condensate.
AB - This study reports on the electropolymerization of a low toxic and biocompatible
polymer with entitle poly arginine-graphene quantum dots (PARG-GQDs) as a novel
strategy for surface modification of glassy carbon (GC) surface and preparation a
new interface for biomedical application. The fabrication of PARG-GQDs on GCE was
performed using Layer-by-layer regime. Scanning electron microscopy (SEM) was
confirmed dispersion of GQDs on the surface of PARG which lead to increase of
surface coverage of PARG. The redox behavior of prepared sensor was then
characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV)
and chronoamperometry (CHA), square wave voltammetry (SWV), linear sweep
voltammetry (LSV). The electroactivity of PARG-GQDs coating towards detection and
determination of malondialdehyde (MDA) as one of the most common biomarkers of
oxidative stress, was then studied. Then, application of prepared sensor for the
detection of MDA in exhaled breath condensate (EBC) is described. Electrochemical
based sensor shows the lower limit of quantification (LLOQ) were 0.329nanomolar.
This work is the first report on the integration of GQDs to poly amino acids.
Further development can lead to monitoring of MDA or other exhaled breath
biomarkers by GQDs functionalized poly amino acids in EBC using electrochemical
methods.
PMID- 28415461
TI - A new bioavailability enhancement strategy of curcumin via self-assembly nano
complexation of curcumin and bovine serum albumin.
AB - Amorphous drug nanoparticles have recently emerged as a superior bioavailability
enhancement strategy for poorly soluble drugs in comparison to the conventional
microscale amorphous solid dispersions. In particular, amorphous drug
nanoparticle complex (or nanoplex) represents an attractive bioavailability
enhancement strategy of curcumin (CUR) - a medicinal herb known for its wide
ranging therapeutic activities - attributed to the high payload, cost-effective
preparation, and supersaturation generation of the nanoplex. To address the poor
colloidal stability of conventional nanoplex formulations, we herein developed a
new class of CUR nanoplex by complexation of CUR with bovine serum albumin (BSA).
The effects of two key variables in drug-protein complexation, i.e. pH and mixing
ratio (MBSA/CUR), on the physical characteristics and preparation efficiency were
investigated. While the CUR-BSA nanoplex preparation was found to favor acidic pH
and MBSA/CUR below unity, the nanoplex's physical characteristics were minimally
affected by pH and MBSA/CUR. At the optimal condition, CUR-BSA nanoplex with size
~90nm, zeta potential ~27mV, and payload ~70% were produced at nearly 100% CUR
utilization rate and ~80% yield. The nanoplex produced a prolonged
supersaturation level at ~9* of the saturation solubility for 4h. The dissolution
rate could be modulated by thermal treatment of the nanoplex post its
preparation. The long-term amorphous state stability, storage colloidal
stability, and preserved bioactivity of the nanoplex were successfully
established. Lastly, the CUR-BSA nanoplex was found to be superior to the
conventional nanoplex in its size, supersaturation generation, colloidal
stability, and yield.
PMID- 28415462
TI - Microencapsulation of eugenol molecules by beta-cyclodextrine as a thermal
protection method of antibacterial action.
AB - Eugenol is natural oil that has excellent antibacterial properties but cannot be
used to fabricate many products that require thermal processing. One possible
alternative to the use of the eugenol molecules in high-temperature processes is
the encapsulation of these molecules in a structure that is not toxic and is
resistant to thermal treatment. This work investigated the encapsulation process
of eugenol molecules in beta-cyclodextrine and the antibacterial properties of
eugenol-beta-cyclodextrine (the eugenol-betaCD complex) against Escherichia coli
and Staphylococcus aureus. The FTIR, DSC, MEV and TGA results show that the
encapsulation method is an excellent alternative to increase the thermal
stability of eugenol molecules. A value of 241.32L.mol-1 was determined for the
formation constant (Kc) of the eugenol-betaCD complex, which confirmed the
success of the encapsulation process. The MEV analysis shows the formation of
approximately 12MUm microcapsules. After the thermal treatment of the eugenol
betaCD complex at a temperature of 80 degrees C for 2h, the complex retained
significant antibacterial action, which confirms the thermal protection of the
eugenol molecules. The minimum inhibitory concentration (MIC) and agar diffusion
results show that the microcapsules containing 17.08mmol.L-1 of eugenol exhibited
excellent antibacterial action against Escherichia coli and Staphylococcus aureus
after thermal treatment.
PMID- 28415463
TI - In vitro characterisation of a sol-gel derived in situ silica-coated silicate and
carbonate co-doped hydroxyapatite nanopowder for bone grafting.
AB - Design and synthesis of materials with better properties and performance are
essential requirements in the field of biomaterials science that would directly
improve patient quality of life. For this purpose, in situ silica-coated silicate
and carbonate co-doped hydroxyapatite (Sc/S.C.HA) nanopowder was synthesized via
the sol-gel method. Characterisation of the prepared nanopowder was carried out
by XRD, FTIR, TEM, SEM, EDX, ICP, zeta potential, acid dissolution test, and cell
culture test. The substitution of the silicate and carbonate ions into
hydroxyapatite structure was confirmed by FTIR analysis. XRD analysis showed that
silica is an amorphous phase, which played a role in covering the surface of the
S.C.HA nanoparticles as confirmed by acid dissolution test. Low thickness and low
integrity of the amorphous silica surface layer facilitated ions release from
S.C.HA nanoparticles into physiological saline solution. Zeta potential of the
prepared nanopowder suspended in physiological saline solution was -27.3+/-0.2mV
at pH7.4. This negatively charged surface, due to the presence of amorphous
silica layer upon the S.C.HA nanoparticles, not only had an accelerating effect
on in vitro biomineralization of apatite, but also had a positive effect on cell
attachment.
PMID- 28415464
TI - In situ forming chitosan hydrogels: Preliminary evaluation of the in vivo
inflammatory response.
AB - This study aims to provide important preliminary in vivo data on the general
biocompatibility and degradation of in situ forming chitosan hydrogels which
differ in the type of cross-linking: physical cross-linking (with glycerol
phosphate disodium salt) and physico/chemical co-cross-linking (with glycerol
phosphate disodium salt and genipin). Additionally, in vitro degradation studies,
using lysozyme, were conducted for comparison. The subcutaneous implantation of
the liquid formulations of both hydrogels in animal model (Wistar rats) was
performed to assess tissue response at the end of two time periods (8 and
30days). Although the properties of both hydrogels are different (namely, pore
size and mechanical strength), leading to remarkably distinct in vitro
degradation behaviors, the in vivo degradation is quite similar for both types.
Regarding biocompatibility, the in vivo evaluation performed by histological
analysis, showed a mild to moderate chronic inflammatory reaction with no foreign
body reaction, demonstrating that both hydrogels show good results for in vivo
biodegradation and biocompatibility, therefore are most adequate for biomedical
applications.
PMID- 28415465
TI - Photochemical coating of Kapton(r) with hydrophilic polymers for the improvement
of neural implants.
AB - The polyimide Kapton(r) was coated photochemically with hydrophilic polymers to
prevent undesirable cell growth on the polyimide surface. The polymer coatings
were generated using photochemically reactive polymers synthesized by a simple
and modular strategy. Suitable polymers or previously synthesized copolymer
precursors were functionalized with photoactive arylazide groups by a polymer
analogous amide coupling reaction with 4-azidobenzoic acid. A photoactive
chitosan derivative (chitosan-Az) and photochemically reactive copolymers
containing DMAA, DEAA or MTA as primary monomers were synthesized using this
method. The amount of arylazide groups in the polymers was adjusted to
approximately 5%, 10% and 20%. As coating on Kapton(r) all polymers effect a
significantly reduced water contact angle (WCA) and consequently a rise of the
surface hydrophilicity compared to the untreated Kapton(r). The presence of the
polymer coatings was also proven by ATR-IR spectroscopy. Coatings with chitosan
Az and the DEAA copolymer cause a distinct inhibition of the growth of
fibroblasts. In the case of the DMAA copolymer even a strong anti-adhesive
behavior towards fibroblasts was verified. Biocompatibility of the polymer
coatings was proven which enables their utilization in biomedical applications.
PMID- 28415466
TI - Effect of lubricant on the reliability of dental implant abutment screw joint: An
in vitro laboratory and three-dimension finite element analysis.
AB - Biomechanical factors play a key role in the success of dental implants. Fracture
and loosening of abutment screws are major issues. This study investigated the
effect of lubricants on the stability of dental implant-abutment connection. As
lubricants, graphite and vaseline were coated on the abutment screw surface,
respectively, and a blank without lubricant served as the control. The total
friction coefficient (MUtot), clamping force, fatigue behavior and detorque of
the joint combined with dynamic cyclic loading were measured under different
lubricating conditions. Further, a three-dimensional finite element analysis was
used to investigate stress distribution, in conjunction with experimental images.
The results showed that the lubricant reduced MUtot, which in turn led to an
increase in clamping force. Decrease in loading increased the fatigue life of the
screw. However, use of lubricant at high load reduced the fatigue life. Ductile
fracture at the first thread of the screw was the chief failure mode, which was
due to maximum von Mises stress. Higher stress levels occurred in the lubricant
groups. Lubricated screws resulted in lower detorque which made the joint easier
to loosen. In conclusion, the lubricant cannot effectively improve the
reliability of dental implant-abutment connection. Keeping the interfaces of
implant-screw uncontaminated and strengthening the surface of the screw may be
recommend for clinical operation and future design.
PMID- 28415467
TI - Poly(l-lactic acid) and polyurethane nanofibers fabricated by solution blow
spinning as potential substrates for cardiac cell culture.
AB - This paper presents a comparison and evaluation of cardiac cell proliferation on
poly(l-lactic acid) (PLLA) and polyurethane (PU) nanofibrous mats fabricated by
solution blow spinning (SBS). Three different cardiac cell lines: rat
cardiomyoblasts (H9C2 line), human (HCM) and rat cardiomyocytes (RCM) were used
for experiments. Cell morphology, orientation and proliferation were investigated
on non-modified and protein-modified (fibronectin, collagen, gelatin, laminin,
poly-l-lysine) surfaces of both types of nanofibers. Obtained results of cell
culture on nanofibers surfaces were compared to the results of cell culture on
polystyrene (PS) surfaces modified in the same way. The results indicated that in
most cases polymeric nanofibers (PLLA and PU) are better substrates for cardiac
cell culture than PS surfaces. All types of investigated cells, cultured on
nanofibers (PLLA and PU), had more elongated shape than cells cultured on PS
surfaces. Moreover, cells were arranged in parallel to each other, according to
fibers orientation. Additionally, it was shown that the protein modifications of
investigated surfaces influenced on cell proliferation. Therefore, we suggest
that the cardiac cell culture on nanofibrous mats fabricated by SBS could be more
advanced experimental in vitro model for studies on the effect of various cardiac
drugs than traditional culture on PS surface.
PMID- 28415468
TI - Characterization of the surface physico-chemistry of plasticized PVC used in
blood bag and infusion tubing.
AB - Commercial infusion tubing and blood storage devices (tubing, blood and platelets
bags) made of plasticized PVC were analyzed by spectroscopic, chromatographic and
microscopic techniques in order to identify and quantify the additives added to
the polymer (lubricants, thermal stabilizers, plasticizers) and to put into
evidence their blooming onto the surface of the devices. For all the samples,
deposits were observed on the surface but with different kinds of morphologies.
Ethylene bis amide lubricant and metallic stearate stabilizers were implicated in
the formation of these layers. In contact with aqueous media, these insoluble
deposits were damaged, suggesting a possible particulate contamination of the
infused solutions.
PMID- 28415469
TI - Pore structures and mechanical properties of porous titanium scaffolds by
bidirectional freeze casting.
AB - Porous titanium scaffolds with long-range lamellar structure were fabricated
using a novel bidirectional freeze casting method. Compared with the ordinarily
porous titanium materials made by traditional freeze casting, the titanium walls
can offer the structure of ordered arrays with parallel to each other in the
transverse cross-sections. And titanium scaffolds with different pore width, wall
size and porosity can be synthesized in terms of adjusting the fabrication
parameters. As the titanium content was increased from 15vol.% to 25vol.%, the
porosity and pore width decreased from 67+/-3% to 50+/-2% and 80+/-10MUm to 67+/
7MUm, respectively. On the contrary, as the wall size was increased from 18+/
2MUm to 30+/-3MUm, the compressive strength and stiffness were increased from
58+/-8MPa to 162+/-10MPa and from 2.5+/-0.7GPa to 6.5+/-0.9GPa, respectively. The
porous titanium scaffolds with long-range lamellar structure and controllable
pore structure produced in present work will be capable of having potential
application as bone tissue scaffold materials.
PMID- 28415470
TI - Spatial stress distribution analysis by thermoelastic stress measurement and
evaluation of effect of stress concentration on durability of various orthopedic
implant devices.
AB - Toward the development of highly durable devices, we investigated the effect of
the thermoelastic constants of implantable raw metals and the surface stress
distribution on the durability of various types of implant device by
thermoelastic stress measurement and by evaluating the effect of the stress
concentration. Surface stress was dynamically calculated from the bending moment,
and the modulus of a section of a device was found to be consistent with the
surface stress obtained by thermoelastic stress measurement. The durability
limits of various types of bone plate and compression hip screw (CHS) calculated
from maximum load vs number of cycles data (L-N data) were close to the notch
fatigue strength of the raw material. The concentration factor of an artificial
hip stem surface was estimated by comparing the L-N data of the stem and the S-N
curve of the raw material. The dynamic analysis of durability by thermoelastic
stress measurement is useful for selecting the worst case (a product
deteriorating to the most severe state) in medical device design.
PMID- 28415471
TI - Synthesis and characterization of Ti-27.5Nb alloy made by CLAD(r) additive
manufacturing process for biomedical applications.
AB - Biocompatible beta-titanium alloys such as Ti-27.5(at.%)Nb are good candidates
for implantology and arthroplasty applications as their particular mechanical
properties, including low Young's modulus, could significantly reduce the stress
shielding phenomenon usually occurring after surgery. The CLAD(r) process is a
powder blown additive manufacturing process that allows the manufacture of
patient specific (i.e. custom) implants. Thus, the use of Ti-27.5(at.%)Nb alloy
formed by CLAD(r) process for biomedical applications as a mean to increase
cytocompatibility and mechanical biocompatibility was investigated in this study.
The microstructural properties of the CLAD-deposited alloy were studied with
optical microscopy and electron back-scattered diffraction (EBSD) analysis. The
conservation of the mechanical properties of the Ti-27.5Nb material after the
transformation steps (ingot-powder atomisation-CLAD) were verified with tensile
tests and appear to remain close to those of reference material.
Cytocompatibility of the material and subsequent cell viability tests showed that
no cytotoxic elements are released in the medium and that viable cells
proliferated well.
PMID- 28415472
TI - Supercritical carbon dioxide extracted extracellular matrix material from adipose
tissue.
AB - Adipose tissue is a rich source of extracellular matrix (ECM) material that can
be isolated by delipidating and decellularizing the tissue. However, the current
delipidation and decellularization methods either involve tedious and lengthy
processes or require toxic chemicals, which may result in the elimination of
vital proteins and growth factors found in the ECM. Hence, an alternative
delipidation and decellularization method for adipose tissue was developed using
supercritical carbon dioxide (SC-CO2) that eliminates the need of any harsh
chemicals and also reduces the amount of processing time required. The resultant
SC-CO2-treated ECM material showed an absence of nuclear content but the
preservation of key proteins such as collagen Type I, collagen Type III, collagen
Type IV, elastin, fibronectin and laminin. In addition, other biological factors
such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast
growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also
retained. Subsequently, the resulting SC-CO2-treated ECM material was used as a
bioactive coating on tissue culture plastic (TCP). Four different cell types
including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical
vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells
and human monocytic leukemia cells (THP-1) were used in this study to show that
the SC-CO2-treated ECM coating can be potentially used for various biomedical
applications. The SC-CO2-treated ECM material showed improved cell-material
interactions for all cell types tested. In addition, in vitro scratch wound assay
using HaCaT cells showed that the presence of SC-CO2-treated ECM material
enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1
derived macrophages showed that the SC-CO2-treated ECM material did not evoke pro
inflammatory responses from the THP-1-derived macrophages. Overall, this study
shows the efficacy of SC-CO2 method for delipidation and decellularization of
adipose tissue whilst retaining its ECM and its subsequent utilization as a
bioactive surface coating material for soft tissue engineering, angiogenesis and
wound healing applications.
PMID- 28415473
TI - Preparation of a novel bioavailable curcuminoid formulation (CureitTM) using
Polar-Nonpolar-Sandwich (PNS) technology and its characterization and
applications.
AB - Health benefits of curcuminoid are highly limited due to their poor aqueous
solubility, very low systemic bioavailability, fast metabolic alterations and
rapid elimination. In this study, a novel bioavailable curcuminoid formulation
CureitTM was prepared by using Polar-Nonpolar-Sandwich (PNS) technology with
complete natural turmeric matrix (CNTM). The synthesized bioavailable curcuminoid
formulation CureitTM was characterizations by Nuclear magnetic resonance
spectroscopy (NMR), scanning electron microscopy (SEM), X-ray diffraction (XRD),
Fourier transform infra-red (IR), current-voltage (I-V) study, Quadrupole Time-of
Flight Mass Spectrometry (Q-TOF), differential scanning calorimeter (DSC) and
thermogravimetric analysis (TGA). NMR study showed the presence of hydrogen
bonding interactions with curcuminoids, polar and non-polar compounds in the PNS
technology. SEM images indicated that CureitTM was almost spherical and well
dispersed with rough morphology, and separated with three layers of PNS
formulation. The chemical profile of CureitTM was analyzed by Q-TOF confirmed the
presence of curcuminoids (curcumin, demethoxycurcumin and bismethoxycurcumin),
lactones, sesquiterpenes and their derivatives derived from polar layer, aromatic
turmerone, dihydroturmerone, turmeronol, curdione and bisacurone derived from non
polar layer. IR, XRD, DSC and TGA also confirmed the presence of curcuminoids
with high stability in the PNS formulation. Various biological activities of
CureitTM were also discussed.
PMID- 28415474
TI - Palladium nanoparticles in electrochemical sensing of trace terazosin in human
serum and pharmaceutical preparations.
AB - In this approach, palladium nanoparticle film was simply fabricated on the
surface of carbon paste electrode by electrochemical deposition method. The film
was characterized using scanning electron microscopy, electrochemical impedance
spectroscopy and cyclic voltammetry. The prepared electrode exhibited an
excellent electrocatalytic activity toward detection of trace amounts of
terazosin, which is an antihypertensive drug. Under the optimum experimental
conditions, a linear range of 1.0*10-8-1.0*10-3molL-1 with a detection limit of
1.9*10-9molL-1 was obtained for determination of terazosin using differential
pulse voltammetry as a sensitive method. The efficiency of palladium nanoparticle
film on the surface of carbon paste electrode successfully proved for
determination of terazosin in pharmaceutical sample and human serum sample with
promising recovery results. The effect of some foreign species has been studied.
PMID- 28415475
TI - Novel non-cytotoxic, bioactive and biodegradable hybrid materials based on
polyurethanes/TiO2 for biomedical applications.
AB - Titanium compounds have demonstrated great interfacial properties with biological
tissues whereas a wide variety of polyurethanes have also been successfully
probed in medical applications. However, studies about hybrids based on
polyurethanes/TiO2 for medical applications are scarce. The aim of this work is
to design novel biodegradable hybrid materials based on polyurethanes/TiO2 (80%
organic-20% inorganic) and to perform a preliminary study of the potential
applications in bone regeneration. The hybrids have been prepared by a sol-gel
reaction using titanium isopropoxide as precursor of the inorganic component and
polyurethane as the organic one. A series of polyurethanes has been prepared
using different polyesters glycol succinate as soft segment, and 1,6
diisocyanatohexane (HDI) and butanediol (BD) as linear hard segment. The
spectroscopy techniques used allow to confirm the formation of the required
polyurethanes by the identification of bands related to carboxylic groups (COOH),
and the amine groups (NH), and also the TiOH bonds and the bonds related to the
interconnected network between the inorganic and the organic components from
hybrids. The results from SEM/EDS show a homogeneous distribution of the
inorganic component into the organic matrix. The nontoxic character of the hybrid
(H400) was probed using MG-63 cell line with over 90% of cell viability. Finally,
the formation of a hydroxyapatite layer in the material surface after 21days of
soaking in SBF shows the bioactive character.
PMID- 28415476
TI - Cellular compatibility of nanocomposite scaffolds based on hydroxyapatite
entrapped in cellulose network for bone repair.
AB - In the past few decades, artificial graft materials for bone tissue engineering
have gained much importance. In this study, novel porous 3D nanocomposite
scaffolds composed of polyacrylamide grafted cellulose and hydroxyapatite were
proposed. They were characterized using scanning electron microscopy (SEM),
Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray
spectroscopy (EDX), and X-ray diffraction analysis (XRD). The swelling behavior
of the scaffolds was examined in both water and phosphate buffer saline (PBS)
solution. The cytotoxicity of the scaffolds was determined by MTT assays on human
fibroblast gum (HuGu) cells. Results showed that the nanocomposite scaffolds were
highly porous with maximum porosity of 85.7% interconnected with a pore size of
around 72-125MUm. The results of cell culture experiments showed that the
scaffolds extracts do not have cytotoxicity in any concentration. Obtained
results suggested that the introduced scaffolds are comparable with the
trabecular bone from the compositional, structural, and mechanical perspectives
and have a great potential as a bone substitute.
PMID- 28415477
TI - Studies on l-histidine capped Ag and Au nanoparticles for dopamine detection.
AB - This work demonstrates the effective surface functionalization of Ag, Au and
bimetallic Ag-Au nanoparticles using l-histidine for colorimetric detection of
dopamine (DA) which plays majorly in recognizing the neurological disorder. l
Histidine (l-His) capped Ag, Au, and bimetallic Ag-Au nanoparticles are
characterized using physico-chemical techniques. The optical behaviour of
nanoparticles has been analysed at various time intervals using UV-Vis absorption
spectroscopy. FT-IR results provide the evidence of chemical bonding between l
histidine and metal nanoparticles. Its structure with the capping of l-His was
clearly shown in HR-TEM images. The average size of nanoparticles has calculated
from TEM image fringes are 11nm, 5nm and 6.5nm respectively, matches with
crystals size calculated from X-ray diffraction pattern. Enhanced optical nature
of nanoparticles provides the best platform to develop a colorimetric-based
biosensor for DA detection. After addition of DA, a rapid colour change has been
noted in colloids of nanoparticles. The substantial changes in absorbance and
lambdamax in metal nanoparticles respect to DA concentration have been observed
and formulated. This is one of the successive methods for trace level
determination of DA and will be going to a significant material for designing
biosensor to determine DA in real extracellular body fluids.
PMID- 28415478
TI - Comparison of unusual carbon-based working electrodes for
electrochemiluminescence sensors.
AB - In this work, unconventional carbon-based materials were investigated for use in
electrochemiluminescence (ECL) working electrodes. Precursors such as bamboo,
pistachio shells, kevlar(r) fibers and camphor were differently treated and used
as working electrodes in ECL experiments. After a proper process they were
assembled as electrodes and tested in an electrochemical cell. Comparison among
them and with a commercial glassy carbon electrode (GCE) shows a very good
response for all of them thus demonstrating their potential use as disposable low
cost electrodes for early detection electrochemical analysis.
PMID- 28415479
TI - Natural polymeric microspheres for modulated drug delivery.
AB - Microspheres can be regarded as a suitable platform for the development of ad hoc
drug delivery systems, since the targeted release of a therapeutic agent can
effectively contribute to support and improve a pharmacological protocol.
However, several crucial factors related to the selection of materials, drugs and
fabrication techniques should be critically analyzed in order to enhance the
expected performance. Dealing with highly compatible materials, e.g. naturally
derived polymers and "green" reagents, can be a valid approach. For this aim,
gelatin, chitosan and blend microspheres were produced by emulsion technique
simply using distilled water and olive oil. Necessarily, due to the intrinsic
instability of the selected materials in aqueous environment, microspheres were
cross-linked with genipin, an extremely low cytotoxic agent, at three different
concentration (i.e., 0.1, 0.5, 1% w/v). Collected microspheres were then loaded
with methylene blue (MB), as drug model. Morphological analysis revealed
homogeneous microspheres characterized by an average diameter comprised in the
range 42-54MUm. In vitro MB temporal delivery was assessed until complete
release, which occurred in about 3days for gelatin and 30days for chitosan
microspheres. Nanoindentation analysis was performed to evaluate how polymers and
genipin influenced the mechanical properties of microspheres. Finally, the effect
of released MB was investigated by means of chicken embryo chorioallantoic
membrane assay, highlighting anti-angiogenic properties for gelatin differently
from chitosan and blend microspheres.
PMID- 28415480
TI - Improvement of mechanical and biological properties of Polycaprolactone loaded
with Hydroxyapatite and Halloysite nanotubes.
AB - Hydroxyapatite (HA) and Halloysite nanotubes (HNTs) percentages have been
optimized in Polycaprolactone (PCL) polymeric matrices to improve mechanical,
thermal and biological properties of the composites, thus, to be applied in bone
tissue engineering or as fixation plates. Addition of HA guarantees a proper
compatibility with human bone due to its osteoconductive and osteoinductive
properties, facilitating bone regeneration in tissue engineering applications.
Addition of HNTs ensures the presence of tubular structures for subsequent drug
loading in their lumen, of molecules such as curcumin, acting as controlled drug
delivery systems. The addition of 20% of HA and different amounts of HNTs leads
to a substantial improvement in mechanical properties with values of flexural
strength up to 40% over raw PCL, with an increase in degradation temperature. DMA
analyses showed stability in mechanical and thermal properties, having as a
result a potential composite to be used as tissue engineering scaffold or
resorbable fixation plate.
PMID- 28415481
TI - Modeling of drug release behavior of pH and temperature sensitive poly(NIPAAm-co
AAc) IPN hydrogels using response surface methodology and artificial neural
networks.
AB - An interpenetrated polymer network (IPN) poly(NIPAAm-co-AAc) hydrogel was
synthesized by two polymerization method: emulsion and solution polymerization.
The pH- and temperature-sensitive hydrogel was loaded by swelling with riboflavin
drug, a B2 vitamin. The release of riboflavin as a function of time has been
achieved under different pH and temperature environments. The determination of
experimental conditions and the analysis of drug delivery results were achieved
using response surface methodology (RSM). In this work, artificial neural
networks (ANNs) in MATLAB were also used to model the release data. The
predictions from the ANN model, which associated input variables, produced
results showing good agreement with experimental data compared to the RSM
results.
PMID- 28415482
TI - Terminal sterilization of equine-derived decellularized tendons for clinical use.
AB - In the last few years, the demand for tissue substitutes has increased and
decellularized matrices has been widely proposed in the medical field to restore
severe damages thanks to high biocompatibility and biomechanical properties
similar to the native tissues. However, biological grafts represent a potential
source of contamination and disease transmission; thus, there is the need to
achieve acceptable levels of sterility. Several sterilization methods have been
investigated with no consensus on the outcomes in terms of minimizing structural
damages and preserving functional features of the decellularized matrix for
transplantation in humans. With the aim of making decellularized tendons safe for
clinical use, we evaluated the cytocompatibility, and biochemical, structural and
biomechanical variations of decellularized equine tendons sterilized with
peracetic acid or beta-irradiation and differently wet- or dry- stored at 4
degrees C or -80 degrees C, respectively. Considering that both sterilization and
long-term storage are crucial steps that could not be avoided, our results
pointed at ionizing beta-rays as terminal sterilization method for decellularized
grafts followed by frozen dry storage. Indeed, this approach can maintain the
integrity of collagen-based structures and can avoid biomechanical changes, thus
making xenogeneic decellularized tendons a promising candidate for clinical use.
PMID- 28415483
TI - An investigation of electrospun Henna leaves extract-loaded chitosan based
nanofibrous mats for skin tissue engineering.
AB - Wound healing characteristics of some plant extracts have been well known for
many years, and they have been utilized for such applications in traditional way.
Recently electrospun nanofibrous mats showed promising properties for tissue
engineering and especially for skin repair. It is expected that incorporation of
plant extracts into such structures could provide higher performance and
synergistic effect for biomedical and wound healing applications. The final
purpose of this study is to fabricate chitosan based nanofiber mats loaded with a
traditional plant extract of Lawsonia inermis (Henna) leaves to enhance the
antibacterial efficacy and wound healing of the precursor nanofibers. The
morphology, structure, mechanical properties and swelling and weight loss degree
of the electrospun nanofibers have been investigated in this study. Antibacterial
activity, cell biocompatibility evaluations and in vivo wound healing activity of
the abovementioned mats were also studied. The FESEM images of Henna leaves
extract-loaded nanofibers proved that homogeneous, smooth and defect free
nanofibers of 64-87nm in diameter have been prepared. Presence of Henna extract
in the electrospun fibers was approved by Fourier Transform Infrared
spectroscopy. Incorporation of Henna extract into the nanofiber mats exhibited
significant synergistic antibacterial activity against bacterial cells. It was
well supported by the results of cell viability and proliferation of human
foreskin fibroblast cells on the prepared scaffolds. Therefore, the results of
this work showed that Henna leaves extract incorporated chitosan nonwoven mats
have a great potential to be used as the biodegradable, biobased and
antibacterial wound healing dressings.
PMID- 28415484
TI - In vitro evaluation of osteoblastic cells on bacterial cellulose modified with
multi-walled carbon nanotubes as scaffold for bone regeneration.
AB - In this paper we explore the use of native bacterial cellulose (BC) in
combination with functionalized multi-walled carbon nanotubes (MWNTs) as an
original biomaterial, suitable three-dimensional (3D) scaffold for osteoblastic
cell culture. Functionalized MWNTs were mixed with native BC (secreted by
Gluconacetobacter xylinus) with the aim of reinforcing the mechanical properties
of BC. The results indicate that BC-MWNTs scaffolds support osteoblast viability,
adhesion and proliferation at higher levels as compared to traditional culture
substrates. Chemically functionalized MWNTs are also an excellent material to be
used as scaffold because these did not affect cell viability and showed an
enhanced osteoblast adhesion. These results suggest the potential for this
combination of biomaterials, i.e. BC and carbon nanomaterials, as scaffolds for
bone regeneration.
PMID- 28415485
TI - Antimicrobial activity of eumelanin-based hybrids: The role of TiO2 in modulating
the structure and biological performance.
AB - Eco-friendly hybrid Eumelanin-TiO2 nanostructures, recently obtained through in
situ methodology based on hydrothermal route, have shown a striking antimicrobial
activity, after exposure to oxidative environment, even under visible light
induction condition. Nevertheless, the role of each component in defining the
efficacy of these biological properties is far from being clearly defined.
Furthermore, the effect of oxidative step on hybrids structure has not yet
addressed. This study aims at elucidating the role of the ratio between eumelanin
precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and TiO2, for its
polymerization in defining morphology and structural organization of TiO2-melanin
nanostructures. Furthermore, tests on a Gram-negative Escherichia coli DH5alpha
strain under UV irradiation and even visible light allowed to assess the
contribution of each component, as well as of the TiO2-DHICA charge transfer
complex to overall biological performance. Finally, results of biocide
characterization were combined with spectroscopic evidences to prove that
oxidative treatment induces a marked structural modification in melanin thus
enhancing overall antimicrobial efficacy.
PMID- 28415486
TI - Surface modification of thin film composite membrane by nanoporous titanate
nanoparticles for improving combined organic and inorganic antifouling
properties.
AB - In this study, nanoporous titanate (NT) nanoparticle synthesized by the
solvothermal method was used to modify polyamide layer of thin film composite
membranes with the aim of improving membrane resistances against organic and
inorganic fouling. Thin film nanocomposite membranes (NMs) were synthesized by
adding mNTs (modified nanoparticles) into polyamide selective layer followed by
characterization using different analytical instruments. The results of XPS and
XRD confirmed the presence of mNTs in the polyamide layer of NMs, while FESEM,
AFM, zeta potential and contact angle measurement further supported the changes
in physical and chemical properties of the membrane surface upon mNTs
incorporation. Results of fouling showed that NM1 (the membrane incorporated with
0.01w/v% mNTs) always demonstrated lower degree of flux decline compared to the
control membrane when membranes were tested with organic, inorganic and
multicomponent synthesized water, brackish water or seawater. Besides showing
greater antifouling resistance, the NM also displayed significantly higher water
flux compared to the control M membrane. The findings of this work confirmed the
positive impact of mNTs in improving the properties of NM with respect to fouling
mitigation and flux improvement.
PMID- 28415487
TI - Simultaneous formation and mineralization of star-P(EO-stat-PO) hydrogels.
AB - Natural bone is an organic-inorganic composite of highly ordered collagen fibrils
and ~60-70% nanocrystalline hydroxyapatite (HA) crystals resulting in a high
fracture resistance for various mechanical loading situations. This study aimed
to synthesize highly mineralized hydrogels to mimic the mechanical properties of
cancellous bone. A six armed star molecule functionalized with isocyanate groups
as reactive termini (NCO-sP(EO-stat-PO)) was used to build up a hydrogel matrix,
which was then subsequently mineralized with hydroxyapatite nanocrystals
following the hydrolysis of incorporated alpha-tricalcium phosphate particles.
The advantage of this dual setting approach in comparison to simply adding
unreactive filler particles to the hydrogel was demonstrated to be a strength
improvement by the factor of 30. After 1-28d setting, the mechanical properties
of a composite with 30wt% NCO-sP(EO-stat-PO) such as elasticity (5.3-1.4%),
compression strength (11-23MPa) and E-modulus (211-811MPa) were found to be
similar to the properties of cancellous bone.
PMID- 28415488
TI - Ultrasound stimulated release of gallic acid from chitin hydrogel matrix.
AB - Ultrasound (US) stimulated drug release was examined in this study using a chitin
hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and
anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin
dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA,
with 24h exposure of the solution to water vapor. The GA release from the GA
chitin hydrogel was examined under different US powers of 0-30W at 43kHz. The
effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25mg/cm3) and
chitin concentrations (0.1, 0.5, and 1wt%) on the release behaviors were recorded
under 43kHz US exposure at 30W. Results show that US accelerated the release
efficiencies for all samples. Furthermore, the release efficiency increased
concomitantly with increasing US power, GA loading amount, and decrease of the
chitin concentration. The highest release rate of 0.74MUg/mL.min was obtained
from 0.54mg/cm3 of GA-loaded hydrogel fabricated from a 0.1wt% chitin mixture
solution under 43kHz US exposure at 30W: nine times higher than that of the
sample without US exposure. The hydrogel viscoelasticity demonstrated that the US
irradiation rigidified the material. FT-IR showed that US can break the hydrogen
bonds in the GA-chitin hydrogels.
PMID- 28415489
TI - Design of Salecan-containing semi-IPN hydrogel for amoxicillin delivery.
AB - Salecan is a new linear extracellular beta-glucan. The unique structure and
beneficial properties of Salecan makes it an appealing material in biomedical
applications. In this work, novel drug devices based on Salecan in a hydrogel
matrix of poly(N-(3-dimethylaminopropyl)acrylamide-co-acrylamide) (Salecan/PDA)
were fabricated via free radical polymerization for controlled release of
amoxicillin. It was demonstrated that amoxicillin was efficiently encapsulated
into the developed hydrogels and released in a Salecan dose-dependent and pH
sensitive manner. Furthermore, cell toxicity and adhesion assays confirmed that
these drug carriers were biocompatible. Altogether, this study opens a new avenue
to fabricate hydrogel devices for controlled delivery of drug.
PMID- 28415491
TI - The substitution of the implant and abutment for their analogs in mechanical
studies: In vitro and in silico analysis.
AB - The use of analogs could reduce the cost of mechanical tests involving implant
supported crowns, but it is unclear if it would negatively affect the data
accuracy. This study evaluated the substitution of the implant by implants
analogs or abutment analogs as a support for crowns in mechanical tests, taking
into account stress distribution and fracture load of monolithic lithium
disilicate crowns. Thirty lithium disilicate monolithic crowns were randomized
into three groups according to the set: Implant+abutment (IA); implant
analog+abutment (IAA); abutment analog (AA). The specimens were subjected to
mechanical fatigue (106cycles, 200N, 2Hz) and thermal fatigue (104cycles, 5
degrees -55 degrees C). A final compression load was applied and the maximum
fracture load was recorded. Data were analyzed using one-way ANOVA (alpha=0.05).
The experiment was validated by finite element analysis and the maximum principal
stress was recorded. No statistically significant difference was observed in the
mean fracture load among groups (P>0.05). The failure mode was similar for all
groups with the origin of crack propagation located at the load point
application. Finite element analysis showed similar stress distribution and
stress peak values for all groups. The use of implant's or abutment's analog does
not influence the fracture load and stress distribution for cemented implant
supported crowns.
PMID- 28415490
TI - Poly(ionic liquid) functionalized polypyrrole nanotubes supported gold
nanoparticles: An efficient electrochemical sensor to detect epinephrine.
AB - Poly(ionic liquids) (PILs) have been applied as the linkers between Au
nanoparticles (NPs) and polypyrrole nanotubes (PPyNTs) for the synthesis of
Au/PILs/PPyNTs hybrids. Due to the presence of PILs, high-density and well
dispersed Au NPs have been deposited on the surface of PILs/PPyNTs by anion
exchange with Au precursor and the in-situ reduction of metal ions. The obtained
Au/PILs/PPyNTs hybrids can be used as a good steady electrode material for
sensitively and selectively detecting epinephrine (EP). The catalytic oxidation
peak currents obtained from differential pulse voltammetry (DPV) increased
linearly with increasing EP concentrations in the range of 35-960MUM with a
detection limit of 298.9nM according to the criterion of a signal-to-noise
ratio=3 (S/N=3), respectively, which showed the excellent electrocatalytic
activity towards this significant hormone in human life.
PMID- 28415492
TI - Antibacterial activity of novel peptide derived from Cry1Ab16 toxin and
development of LbL films for foodborne pathogens control.
AB - Escherichia coli is one of the most common etiological agents of diarrhea in
developing countries. The appearance of resistant E. coli prevents treatment of
these infections. Biotechnological products incorporating antimicrobial peptides
are currently being considered in applications to prevent intestinal infections
by these bacteria. The aim of this study was to evaluate the antibacterial
activity of the peptide PcL342-354C, which is derived from the toxin Cry1Ab16
from Bacillus thuringiensis, against E. coli strains. We also report the
preparation, characterization and evaluation of the antibacterial activity of LbL
films containing PcL342-354C. The results showed that the PcL342-354C peptide
inhibited the growth of different strains of E. coli with minimal inhibitory
concentration ranging from 15.62-31.25MUg/mL and minimal bactericidal
concentration was 250MUg/mL, indicating a potential antibacterial activity. The
morphology of an ITO/Cashew gum/PcL342-354C film was analysed using atomic force
microscopy which showed an increase of roughness due to the increase in the
number of layers. The LbL films showed significant antibacterial activity against
E. coli NCTC 9001 in both conditions tested (10 and 20 bilayers). Our results
indicate that the peptide exhibits an antibacterial potential that can be tapped
to develop biomaterials with antibacterial activity for use against foodborne
pathogens.
PMID- 28415493
TI - Multifunctional BaYbF5: Gd/Er upconversion nanoparticles for in vivo tri-modal
upconversion optical, X-ray computed tomography and magnetic resonance imaging.
AB - Development of high-quality upconversion nanoparticles (UCNPs) with combination
of the merits of multiple molecular imaging techniques, such as, upconversion
luminescence (UCL) imaging, X-ray computed tomography (CT), and magnetic
resonance (MR) imaging, could significantly improve the accuracy of biological
diagnosis. In this work, multifunctional BaYbF5: Gd/Er (50:2mol%) UCNPs were
synthesized via a solvothermal method using oleic acid (OA) as surface ligands
(denoted as OA-UCNPs). The OA-UCNPs were further treated by diluted HCl to form
ligand-free UCNPs (LF-UCNPs) for later bioimaging applications. The cytotoxicity
assay in HeLa cells shows low cell toxicity of these LF-UCNPs. Owing to the
efficient UCL of BaYbF5: Gd/Er, the LF-UCNPs were successfully used as
luminescent bioprobe in UCL bioimaging. And, X-ray CT imaging reveals that
BaYbF5: Gd/Er UCNPs can act as potential contrast agents for detection of the
liver and spleen in the live mice owing to the high-Z elements (e.g., Ba, Yb, and
Gd) in host matrix. Moreover, with the addition of Gd, the as-designed UCNPs
exhibit additional positive contrast enhancement in T1-weighted MR imaging. These
findings demonstrate that BaYbF5: Gd/Er UCNPs are potential candidates for tri
modal imaging.
PMID- 28415494
TI - Investigation on Au-nano incorporated pH-sensitive (itaconic acid/acrylic
acid/triethylene glycol) based polymeric biocompatible hydrogels.
AB - The pH-sensitive gold nano hydrogel based on itaconic acid, acrylic acid and
triethylene glycol (GIAT) has been prepared by free radical polymerization viz.
organic solventless approach with different monomer ratios. The nature of bonding
and structural identification of GIAT hydrogels were characterized by FT-IR
spectroscopy. The surface morphology of gold gel was examined using scanning
electron microscopy (SEM). In addition, transmission electron microscopy (TEM)
was used to identify the size of gold nano particles. The in vitro
biocompatibility of GIAT hydrogel has been evaluated in 3T3 fibroblast cell
lines. The obtained results show that gold nano particle incorporated hydrogel
possess ~99% of cell proliferation. Followed by, the impact of gold nano
particles on swelling, surface morphology was studied. The consecutive
preparation of hydrogel, effect of different pH conditions, and stoichiometry of
monomeric units have also been discussed. The degree of swelling was measured in
carbonate buffer solutions for 24h period with varying pH such as 1.2, 6.0, 7.4
and 10.0. The obtained results showed that the stoichiometry of itaconic acid and
gold nano particles plays an essential role in modifying the nature of GIAT
polymeric hydrogels. In conclusion, promising Au-nano incorporated pH-sensitive
bio polymeric hydrogels were prepared and characterized. The unique properties of
these Au-nano hydrogel make them attractive use in biomedical applications.
PMID- 28415495
TI - Silver sulfadiazine immobilized glass as antimicrobial fillers for dental
restorative materials.
AB - Bacterial colonization and biofilm formation on dental resin composites cause
secondary caries that shortens the service life of dental restorative materials.
In this study, commercial barium borosilicate based glass powders, fillers widely
used in dental composites, were covalently immobilized with silver sulfadiazine
to provide antimicrobial effects. The chemical reactions were followed by FT-IR
study, elemental analysis, and energy dispersive spectroscopy (EDS), and the
reaction pathway was confirmed by model compound studies. The resulting glass
powders demonstrated potent antimicrobial effects against Streptococcus mutans
(S. mutans). BisGMA (2,2-bis[4-(2-hydroxy-3-methacrylyloxypropoxy)phenyl]
propane)-based dental resins containing 2% to 10% of the new silver sulfadiazine
glass powders exhibited powerful and durable antimicrobial efficacy against S.
mutans. The mechanical properties of the antimicrobial resins were not negatively
affected by the silver sulfadiazine glass powders, making them attractive
candidates as antimicrobial fillers for dental composites and other related
biomedical applications.
PMID- 28415496
TI - A novel long-acting biodegradable depot formulation of anastrozole for breast
cancer therapy.
AB - The purpose of the present study was to fabricate PLGA 50:50 and PLA microspheres
for controlled delivery of anastrozole. The microspheres were prepared by oil-in
water (o/w) emulsion/solvent evaporation technique and evaluated for particle
size and encapsulation. The optimised formulations were studied for solid state
characterization, in vitro release and pharmacokinetic studies. The maximum
encapsulation efficiency for PLGA 50:50 and PLA microspheres with 40:1 polymer -
drug ratio was observed to be 78.4+/-2.5 and 87.7+/-2.6%. The solid state
characterization confirmed dispersion of drug at the molecular level in the
polymeric matrix. Microspheres were spherical in shape with a very smooth surface
texture. Drug release was found to be in a sustained fashion, releasing
constantly up to 720h (30days) for PLGA and 60days for PLA microspheres. The
pharmacokinetic study data revealed that the intramuscular administration of PLA
microspheres showed improved pharmacokinetic profile as compared to PLGA
microspheres, and therefore this formulation can be considered as the best
optimised formulation with sustained exposure of the drug in vivo compared to
other microspheres. From experimental results, PLA microspheres demonstrate the
feasibility of employing biodegradable depot polymeric microspheres of
anastrozole for long-term treatment of breast cancer.
PMID- 28415497
TI - Modeling and optimization of gelatin-chitosan micro-carriers preparation for soft
tissue engineering: Using Response Surface Methodology.
AB - Electrospray ionization is a wide spread technique for producing polymeric
microcarriers (MCs) by applying electrostatic force and ionic cross-linker,
simultaneously. In this study, fabrication process of gelatin-chitosan MCs and
its optimization using the Response Surface Methodology (RSM) is reported.
Gelatin/chitosan (G/C) blend ratio, applied voltage and feeding flow rate, their
individual and interaction effects on the diameter and mechanical strength of the
MCs were investigated. The obtained models for diameter and mechanical strength
of MCs have a quadratic relationship with G/C blend ratio, applied voltage and
feeding flow rate. Using the desirability curve, optimized G/C blend ratios that
are introduced, include the desirable quantities for MCs diameter and mechanical
strength. MCs of the same desirable diameter (350MUm) and different G/C blend
ratio (1, 2, and 3) were fabricated and their elasticity was investigated via
Atomic Force Microscopy (AFM). The biocompatibility of the MCs was evaluated
using MTT assay. The results showed that human Umbilical Cord Mesenchymal Stem
Cells (hUCMSCs) could attach and proliferate on fabricated MCs during 7days of
culturing especially on those prepared with G/C blend ratios of 1 and 2. Such
gelatin-chitosan MCs may be considered as a promising candidate for injectable
tissue engineering scaffolds, supporting attachment and proliferation of hUCMSCs.
PMID- 28415498
TI - Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate
A-deoxycholic acid conjugate for triggered release of doxorubicin.
AB - Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed.
CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The
bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous
medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is
0.047mg/mL, and its mean diameter is 387nm. The anticancer drug doxorubicin (DOX)
was chosen as a model drug, and was effectively encapsulated into the micelles
with high loading efficiency. Reduction-sensitive micelles and reduction
insensitive control micelles displayed similar DOX release behavior in phosphate
buffered saline (PBS, pH7.4). Notably, DOX release from the reduction-sensitive
micelles in vitro was accelerated in the presence of 20mM glutathione-containing
PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles
exhibited intracellular reduction-responsive characteristics in human gastric
cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM).
Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than
reduction-insensitive control micelles in HGC-27 cells. These results suggested
that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular
targeted carriers of anticancer drugs.
PMID- 28415499
TI - Antibacterial effect of PEO coating with silver on AA7075.
AB - In this work, plasma electrolytic oxidation (PEO) coatings were produced on
AA7075 using alkaline solution containing silicates compounds and silver
micrometric particles in order to give to the coating an antimicrobial effect. In
the optic of circular economy, silver chloride derived from the acid pre
treatment of electronic scraps was used as raw material and successively silver
powders were synthesized from silver chloride solution using glucose syrup as
reducing agent. The coatings were characterized by scanning electron microscope
(SEM), X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS),
potentiodynamic polarization test and antimicrobial tests. The results evidenced
that the obtained coatings were homogenous and give to the samples higher
corrosion resistance than untreated alloy. The silver particles, found both
inside and outside of the pores that characterize the PEO layer, produced an
efficacious antimicrobial effect both against E. coli and S. aureus.
PMID- 28415500
TI - Sustained release of simvastatin from hollow carbonated hydroxyapatite
microspheres prepared by aspartic acid and sodium dodecyl sulfate.
AB - Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV)
sustained-release vehicles were fabricated through a novel and simple one-step
biomimetic strategy. Firstly, hollow CaCO3 microspheres were precipitated through
the reaction of CaCl2 with Na2CO3 in the presence of aspartic acid and sodium
dodecyl sulfate. Then, the as-prepared hollow CaCO3 microspheres were transformed
into HCHAp microspheres with a controlled anion-exchange method. The HCHAp
microspheres were 3-5MUm with a shell thickness of 0.5-1MUm and were constructed
of short needle nanoparticles. The HCHAp microspheres were then loaded with SV,
exhibiting excellent drug-loading capacity and sustained release properties.
These results present a new material synthesis strategy for HCHAp microspheres
and suggest that the as-prepared HCHAp microspheres are promising for
applications in drug delivery.
PMID- 28415501
TI - Fabrication of new magnetite-graphene nanocomposite and comparison of its laser
hyperthermia properties with conventionally prepared magnetite-graphene hybrid.
AB - A single step supercritical method was introduced for synthesis of "magnetite -
reduced graphene oxide (M-rGO)" composite in supercritical methanol. Modified
surface, smaller size, lesser cytotoxicity, and homogenous dispersion of Fe3O4
nanoparticles on the graphene surface were advantages of this new M-rGO composite
in comparison to the materials synthesized by conventional wet chemical method (M
GO). Nanocomposites were injected in tissue equivalent phantoms of agarose gel in
10mg/g dosage, and were irradiated by a 1600mW laser beam at wavelength of 800
810nm. The M-rGO and M-GO were found to be the most and the least efficient
samples for increasing the temperature of the phantom. As for mathematical
analysis of the heating process, a heat transfer model was developed and solved
by the COMSOL Multiphysics software. Results showed an appreciable agreement with
the experiments and revealed enhancement in thermal conductivity and light
absorption coefficient of tissue by injecting of M-rGO sample. Our findings
showed that M-rGO is a promising material for laser hyperthermia, which can
deposit adequate heat dose with desirable effect in the tumorous cells in a short
period.
PMID- 28415502
TI - Antimicrobial textiles: Biogenic silver nanoparticles against Candida and
Xanthomonas.
AB - This paper introduces cotton fibers impregnated with biogenic silver
nanoparticles (AgNPs), synthesized from a Fusarium oxysporum fungal filtrate (FF)
solution, and open up the possibility for their use in medical environment and
agriculture clothing as means to avoid microbial spreading. After thorough AgNPs
characterization, regarding their physical, chemical and biochemical properties,
Minimum Inhibitory Concentrations (MIC) against some human and orange tree
pathogens were determined. We report the strong AgNPs activity against Candida
parapsilosis and Xanthomonas axonopodis pv. citri (Xac) that was morphologically
characterized, pointing to strong AgNPs effects on microorganisms' membranes.
Cotton fibers were then impregnated with AgNPs suspension and these maintained
strong antimicrobial activity even after repeated mechanical washing cycles (up
to 10). Reported data might point to an application for biogenic AgNPs as potent
agrochemicals, as well as, to their application in textiles for antiseptic
clothing for medical and agronomic applications.
PMID- 28415503
TI - Synthesis of nanosized 58S bioactive glass particles by a three-dimensional
ordered macroporous carbon template.
AB - Nanosized 58S bioactive glass (BG) particles were synthesized by using a three
dimensional ordered macroporous carbon template (OMC) with a pore size of 400nm.
The obtained 58S BG particles possessed a diameter of 300nm, narrow size
distribution and uniform spherical morphology. 58S/gelatin composites were
prepared and showed much better mechanical properties than pure gelatin. The
narrow size distribution of the 58S particles replicated from OMC was confirmed
crucial to the mechanical properties of the 58S/gelatin composite, comparing to
the contrast sample prepared with polydispersed particles. The outstanding
bioactivity of the 58S BG particles was confirmed by inducing the formation of
carbonated hydroxyapatite on the 58S/gelatin composite surface. This work showed
a successful example that OMC template could be used to synthesize particles
requiring a robust reaction condition, and a particle synthesis method that could
well control particle size distribution was important for preparing materials
with outstanding mechanical properties.
PMID- 28415504
TI - In vitro evaluation of hydroxyapatite coatings with (002) crystallographic
texture deposited by micro-plasma spraying.
AB - Hydroxyapatite (HA) coatings are usually deposited on the metallic implant to
increase the biocompatibility and protect the bloodstream from harmful metal
ions. Atmospheric plasma spray (APS) is known as a cost effective deposition
method. However, the low crystallinity of APS deposited coating accelerates its
dissolution in body fluid. We used micro-plasma spray (MPS) to develop chemically
stable HA coatings, and performed APS as reference. Results showed that MPS
deposited coatings exhibited (002) crystallographic texture while the reference
sample did not. The texture intensity and crystallinity were improved by
shortening stand-off distance. These suggested that different formation
procedures of HA coatings were involved and three mechanisms were proposed by
sketching typical splats. To evaluate the chemical stability of the coatings in a
physiological environment, in vitro experiments were performed in Hanks'
solution. Well crystallized (~100%) HA coating with the strongest
crystallographic texture exhibited superior stability up to 14days. Crystals with
(002) orientation was more stable than that with (211) orientation. Hence
columnar structure with nanopores emerged on the coating surface after
incubation, and this may facilitate the future osteoblast growth. Furthermore, HA
coating with weak and no crystallographic texture induced apatite layer. However,
vertical cracks and cleavage at coating-apatite interface may cause coating
separation.
PMID- 28415505
TI - A new method to produce macroporous Mg-phosphate bone growth substitutes.
AB - This paper is a sequel to our previous effort in developing Mg-phosphate
orthopedic cements using amorphous Mg-phosphate (AMP) as the precursor. In this
paper, we report a new real-time in situ technique to create macroporous bone
growth substitute (BGS). The method uses biodegradable Mg-particles as the
porogen. As opposed to the conventional wisdom of providing corrosion protection
layers to biodegradable Mg-alloys, the present method uses the fast corrosion
kinetics of Mg to create macropores in real time during the setting of the
cement. An aqueous solution of PVA was used as the setting solution. Using this
technique, a macroporous cement containing up to 91% porosity is obtained, as
determined by pycnometry. Due to formation of H2 gas bubbles from corrosion of
Mg, the cement becomes macroporous. The pore sizes as big as 760MUm were
observed. The results of SBF soaking indicated change in crystallinity as
confirmed via scanning electron microscopy (SEM) and X-ray diffraction (XRD). Our
in vitro cytocompatibility evaluation also revealed that the macroporous bone
growth substitute composed of bobierrite is cytocompatible and can improve gene
expression.
PMID- 28415506
TI - The bactericidal mechanism of action against Staphylococcus aureus for AgO
nanoparticles.
AB - To identify the mechanistic effects of AgO nanoparticles on Gram-positive
bacteria, S. aureus cells suspended in phosphate buffer solution (PBS) and
deionized water were separately treated using AgO nanoparticles at different
concentrations. The phase composition changes of the bactericide after killing S.
aureus and the cellular responses of S. aureus to AgO were characterized by X-ray
diffraction, atomic absorption spectrophotometer, scanning electron microscopy,
transmission electron microscopy, and energy dispersive spectroscopy. The results
show that AgO nanoparticles could kill S. aureus suspended in PBS and deionized
water. The bactericidal effect of AgO bactericide against S. aureus in water was
better than that in PBS, due to the formation of Ag3PO4 from the reaction between
AgO and PBS. AgO nanoparticles exerted their bactericidal activity by multiple
processes. AgO nanoparticles adhered to the surface of S. aureus cells firstly,
then induced physical alterations in cell morphology and released silver ions,
leading to initial injuries of cell membrane. Once membrane damage occurred, they
entered the cells, and damaged the intracellular materials, eventually causing
severe morphological and structural injuries to the cells and leakage of
cytoplasm.
PMID- 28415507
TI - Influences of doping mesoporous magnesium silicate on water absorption, drug
release, degradability, apatite-mineralization and primary cells responses to
calcium sulfate based bone cements.
AB - In this study, composite cements containing mesoporous magnesium silicate (m-MS)
and calcium sulfate (CS) were fabricated. The results revealed that the setting
time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the
increase of m-MS content while the compressive strength suffered a little loss.
The doping of m-MS improved the water absorption, drug release (vancomycin) and
degradability of the m-MSC in Tris-HCl solution (pH=7.4). In addition, addition
of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid
(SBF), indicating good bioactivity. For cell cultural experiments, the results
revealed that the m-MSC promoted the cells adhesion and proliferation, and
improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing
good cytocompatibility. It could be suggested that the m-MSC might be promising
cements biomaterials for bone tissue regeneration.
PMID- 28415508
TI - Magneto-elastic biosensors: Influence of different thiols on pathogen capture
efficiency.
AB - Magneto-elastic biosensors have mass sensitivity to biological species, offering
reliability and reproducibility in the detection of pathogens such as Escherichia
coli. In this work, amorphous ribbons of Metglas 2826MB3 were coated with layers
of Cr and Au by DC magnetron sputtering and cut to 5mm*1mm. The influence of
different thiols on captured pathogens was studied. The compounds cystamine
(CYS), cysteamine (CYSTE) and mercaptopropionic acid (MPA) were deposited on Au
covered surfaces, followed by antibodies. The roughness parameters Ra and Rq were
determined using atomic force microscopy (AFM) and micrographs from scanning
electron microscopy with a field emission gun (FESEM) were also utilized.
Biosensors formed with MPA showed an increased efficiency for attracting E. coli
compared to biosensors with CYS and CYSTE, but large standard deviations were
observed, making reproducibility and reliability difficult for that biosensor.
Sensors tested with CYSTE showed greater efficiency and a lower detection limit
than sensors with CYS. The results indicated that the size of the carbon chain
and the terminal grouping influence the effectiveness of immobilization on
magneto-elastic biosensors.
PMID- 28415509
TI - Preparation and evaluation of a novel anticancer drug delivery carrier for 5
Fluorouracil using synthetic bola-amphiphile based on lysine as polar heads.
AB - A novel bolaamphiphile surfactant N,N'-(dodecane-1, 12-diyl) bis (2,6
diaminohexanamide) (DADL) was designed and synthesized using l-lysine and 1,12
diaminododecane as the hydrophilic and hydrophobic part, respectively. After
separation and purification, the structure of the synthetic bolaamphiphile
surfactant was verified by FTIR, MS and 1H NMR. The synthetic bolaamphiphile was
able to self-assemble to form vesicles. After formulation screening, vesicles
loaded with 5-Fluorouracil (5-Fu) were prepared with Tween 60 and DADL by
sonication and were examined by dynamic light scattering and transmission
electron microscopy. Micro-FTIR was applied to investigate the conformation of
the bola molecules within the vesicle membrane. The release profile of the
vesicles showed a pH-sensitive and sustained release. No significant toxicity was
observed in an in vitro cell viability assay. The antitumor efficacy of the 5-Fu
loaded vesicles on H22 tumor-bearing mice was remarkably high due to the EPR
effects. These results show that our novel bolaamphiphile derived from lysine has
excellent potential as a pH-sensitive drug carrier.
PMID- 28415510
TI - On the passive and semiconducting behavior of severely deformed pure titanium in
Ringer's physiological solution at 37 degrees C: A trial of the point defect
model.
AB - The effects of sever plastic deformation through multi-pass accumulative roll
bonding on the passive and semiconducting behavior of pure titanium is evaluated
in Ringer's physiological solution at 37 degrees C in the present paper. Produced
results by polarization plots and electrochemical impedance spectroscopy
measurements revealed a significant advance in the passive response of the nano
grained sample compared to that of the annealed pure titanium. Also, Mott
Schottky test results of the nano-grained pure titanium represented a lower donor
density and reduced flat-band potential in the formed passive film in comparison
with the annealed sample. Moreover, based on the Mott-Schottky analysis in
conjunction with the point defect model, it was suggested that with increase in
formation potential, the calculated donor density of both annealed and nano
grained samples decreases exponentially and the thickness of the passive film
linearly increases. These observations were consistent with the point defect
model predictions, considering that the point defects within the passive film are
metal interstitials, oxygen vacancies, or both. From the viewpoint of passive and
semiconducting behavior, nano-grained pure titanium appeared to be more suitable
for implant applications in simulate human body environment compared to annealed
pure titanium.
PMID- 28415511
TI - Facile synthesis and characterization of novel rapid-setting spherical sub-micron
bioactive glasses cements and their biocompatibility in vitro.
AB - Dental pulp vitality is extremely important for the tooth viability, since it
provides nutrition and forms the dentin. Bioactive glasses (BGs) may be promising
materials for pulp repair due to their excellent abilities of rapidly bonding to
bone and stimulating new bone growth. However, the unsatisfied handling property,
low plasticity, and poor rapid-setting property of traditional BGs limit its
application in vital pulp therapy. Spherical bioactive glasses (SBGs) exhibited
higher osteogenesis and odontogenic differentiation than irregular BGs. This
study focuses on the application of SBGs with rapid setting property for dental
pulp repair. Here, SBGs with various compositions were successfully synthesized
by a sol-gel process using dodecylamine (DDA) served as both a catalyst and a
template. The maximum content of CaO in SBGs was about 15%. The non-bridge oxygen
amounts of the SiO network and the apatite-forming ability increased with the
content proportion of CaO and P2O5. Bioactive glass pulp capping materials
(BGPCMs) were prepared by mixing the SBGs powders and the phosphate buffer
solution (PBS). The K3CaH(PO4)2 and hydroxyapatite (HA) formed between SBGs
particles as soon as they were mixed with PBS solution. The compressive strengths
of fully set BCPCM-2 molded were measured to be 31.76+/-1.9577MPa after setting
for 24h. The K3CaH(PO4)2 and the low crystallinity HA phases at the initial stage
of solidification transformed to crystalline HA for 3days, and the compressive
strength was still higher than 10MPa. Additionally, SBG-2 with a designed molar
composition of 35% SiO2, 55% CaO and 10% P2O5 more promoted dental pulp cell
proliferation, and could be potential pulp capping applications.
PMID- 28415512
TI - Study of epithelial differentiation and protein expression of keratinocyte
mesenchyme stem cell co-cultivation on electrospun nylon/B. vulgaris extract
composite scaffold.
AB - Employing of the composite electrospun scaffold containing herbal extract in
conjugation with co-culturing of cells can open up new window to the design of
efficient biomaterials for skin tissue regeneration. Here, we introduce the
synergistic effect of composite electrospun nanofibrous scaffold of nylon66
loaded with Beta vulgaris (B. vulgaris) (extract of beet roots, a plants whose
widely used in Iranian folk medicine as wound healing medicine) and co-culture of
mesenchymal stem-cells (MSCs)-human keratinocyte (H-keratino) differentiation
towards epithelial lineage. In vitro biocompatibility was examined through MTT
assay and epithelial differentiation checked by real-time PCR and
immunocytochemistry (ICC) assay after co-culturing of MSCs and H-keratino on
proposed scaffold. Significant enhancement in cell proliferation was detected
after cell culturing on the composite type of electrospun scaffold containing B.
vulgaris. Moreover, after 14days of co-culturing process, gene expression results
revealed that both composite and non-composite nylon66 electrospun scaffold
promote epithelial differentiation compared to mono-cell culturing of H-keratino
in terms of several markers as Cytokeratin 10, Cytokeratin 14 and Involucrin and
ICC of some dermal proteins like Cytokeratin 14 and Loricrin. To the best of our
knowledge, findings of this study will introduce new way for the generation of
novel biomaterials for the development of current skin tissue engineering.
PMID- 28415513
TI - Evaluation of radiolabeled curcumin-loaded solid lipid nanoparticles usage as an
imaging agent in liver-spleen scintigraphy.
AB - Curcumin-loaded solid lipid nanoparticles (C-SLNs) were prepared using micro
emulsion and ultrasonication methods in the first stage of this study to
determine the role of C-SLN on liver-spleen scintigraphy. It was concluded that
the curcumin that was encapsulated in solid lipid nanoparticles had a beta'
polymorph structure according to the X-ray diffraction (XRD) analysis. It was
concluded that these particles were at nano scale according to the laser
diffraction (LD) analysis. Fourier transform infrared spectroscopy (FT-IR)
analysis suggested an interaction between the curcumin and the solid lipid
matrix, and the curcumin was loaded on the solid lipid nanoparticles. Moreover,
the particles were concluded to be spherical and at nanoscale according to the
scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
images. On the other hand, thermogravimetric analysis (TGA) suggested that the
curcumin loaded solid nanoparticles were stable against the temperature. C-SLNs
were labeled with Technetium-99m (99mTc) radioisotope in the second stage of the
study, then using scintigraphic methods in-vivo studies were performed on New
Zealand rabbit and made a comparison with Phytate colloid, routinely used in
liver-spleen scintigraphy. After analyzing the images and the biological
distributions obtained from the experiments, uptake was observed in the liver and
the spleen. Following from the experiment results, 99mTc-labeled C-SLNs was
concluded to be a possible imaging agent. In particular, it could be a new
radiopharmaceutical alternative to 99mTc-labeled compounds that are used in liver
and spleen imaging in colloid scintigraphy.
PMID- 28415514
TI - Synthesis and characterization of cycloaliphatic hydrophilic polyurethanes,
modified with l-ascorbic acid, as materials for soft tissue regeneration.
AB - In this paper we described synthesis and characteristic of obtained hydrophilic
polyurethanes (PURs) modified with ascorbic acid (commonly known as vitamin C).
Such materials may find an application in the biomedical field, for example in
the regenerative medicine of soft tissues, according to ascorbic acid wide
influence on tissue regeneration Flora (2009), Szymanska-Pasternak et al. (2011),
Taikarimi and Ibrahim (2011), Myrvik and Volk (1954), Li et al. (2001), Cursino
et al. (2005) . Hydrophilic PURs were obtained with the use of amorphous
alpha,omega-dihydroxy(ethylene-butylene adipate) (dHEBA) polyol, 1,4-butanediol
(BDO) chain extender and aliphatic 4,4'-methylenebis(cyclohexyl isocyanate)
(HMDI). HMDI was chosen as a nontoxic diisocyanate, suitable for biomedical PUR
synthesis. Modification with l-ascorbic acid (AA) was performed to improve
obtained PUR materials biocompatibility. Chemical structure of obtained PURs was
provided and confirmed by Fourier transform infrared spectroscopy (FTIR) and
Proton nuclear magnetic resonance spectroscopy (1HNMR). Differential scanning
calorimetry (DSC) was used to indicate the influence of ascorbic acid
modification on such parameters as glass transition temperature, melting
temperature and melting enthalpies of obtained materials. To determine how these
materials may potentially behave, after implementation in tissue, degradation
behavior of obtained PURs in various chemical environments, which were
represented by canola oil, saline solution, distilled water and phosphate
buffered saline (PBS) was estimated. The influence of AA on hydrophilic
hydrophobic character of obtained PURs was established by contact angle study.
This experiment revealed that ascorbic acid significantly improves hydrophilicity
of obtained PUR materials and the same cause that they are more suitable
candidates for biomedical applications. Good hemocompatibility characteristic of
studied PUR materials was confirmed by the hemocompatibility test with human
blood. Microbiological tests were carried out to indicate the microbiological
sensitivity of obtained PURs. Results of performed studies showed that obtained
AA-modified PUR materials may find an application in soft tissue regeneration.
PMID- 28415515
TI - Highly selective thiocyanate optochemical sensor based on manganese(III)-salophen
ionophore.
AB - We report on the development of optochemical sensor based on Mn(III)-salophen
ionophore. The sensor was prepared by embedding the ionophore in a plasticized
poly (vinyl chloride) impregnated with the chromoionophore ETH7075. Optical
response to thiocyanate occurred due to thiocyanate extraction into the polymer
via formation of strong complex with the ionophore and simultaneous protonation
of the indicator dye yielding the optical response at 545nm. The developed
optochemical sensor exhibited high selectivity for thiocyanate over other anions
including the most lipophilic species such as salicylate and perchlorate. For
instance, the optical selectivity coefficients, logKSCN,anionopt, were as follow:
ClO4-=-5.8; Sal-=-4.0; NO3-?-6. Further, the thiocyanate optical selectivity
obtained using the present optochemical sensor was greatly enhanced in comparison
with that obtained using an anion-exchanger based sensor. Also, the optimized
optochemical sensor exhibited micro-molar detection limit with 2min response time
at pH4.5 using acetate buffer. The reversibility of the optimized sensor was poor
due to strong ligation of the thiocyanate to the central Metal ion, log K=14.1,
which can be overcome by soaking the optode in sodium hydroxide followed by
soaking in buffer solution. The developed sensor was utilized successfully for
the determination of thiocyanate in human saliva and in spiked saliva samples.
PMID- 28415516
TI - Acceleration of bone regeneration in bioactive glass/gelatin composite scaffolds
seeded with bone marrow-derived mesenchymal stem cells over-expressing bone
morphogenetic protein-7.
AB - In this research, the osteoinduction effect of a novel variant of bone
morphogenetic protein-7 (BMP-7), delivered through bone marrow mesenchymal stem
cells (BM-MSCs) seeded on bioactive glass/gelatin nanocomposite scaffolds, was
evaluated in a calvarial critical size defect in rats. After being harvested and
characterized in vitro, BM-MSCs were infected by a plasmid vector containing BMP
7 encoding gene enriched with a heparin-binding site (B2BMP-7) to assess its
osteogenic effects in vivo. The animals were randomly categorized into three
groups receiving the scaffold alone (group I), the scaffold seeded with BM-MSCs
(group II), and the scaffold seeded with manipulated BM-MSCs (group III). After
2, 4 and 12 postoperative weeks, the animals were sacrificed and the harvested
specimens were analyzed using histological and immunohistochemical staining. The
results of in vitro tests (preliminary screening) showed that the synthesized
scaffolds were biocompatible constructs supporting cell attachment and expansion.
The in vivo results revealed higher osteogenesis in the defects filled with the
B2BMP-7 excreting BM-MSCs/scaffolds compared to the other two groups. After
12weeks of implantation, fully mature newly formed bone was detected throughout
the damaged site, which indicates a synergistic effect of cells, scaffolds and
growth factors in the process of tissue regeneration. Therefore, bioactive glass
containing scaffolds pre-seeded with manipulated BM-MSCs exhibit an effective
combination to improve osteogenesis in bone defects, and the approach followed in
this work could have a significant impact in the development of novel tissue
engineering constructs.
PMID- 28415517
TI - Fabrication of novel biodegradable porous bone scaffolds based on amphiphilic
hydroxyapatite nanorods.
AB - This paper describes a new synthetic strategy and biological application for
novel amphiphilic hydroxyapatite (HAp) nanorods. The prepared HAp nanorods were
able to be dispersed in water, ethyl alcohol and cyclohexane. The co-anchoring of
the multidentate ligands of PEG 20000 and hydrophobic oleic acid (OA) on the
rods' surfaces endowed them with excellent amphibious properties. Utilizing
amphiphilic HAp nanorods with excellent biocompatibility as the inorganic phase,
human-like collagen (HLC) as the organic phase and natural genipin as the cross
linker, optimal HLC/HAp porous scaffolds (HLC: HAp=1:4, w/w) were fabricated. The
compression stress and three-point bending strength of the scaffolds with pore
diameters of 150 to 200MUm reached approximately 3.4MPa and 5.4MPa, respectively,
and their porosity was 77.35+/-3.75%. Cytological tests showed that HLC/HAp
scaffolds could contribute to cell proliferation and differentiation. The results
indicated that these novel amphiphilic HAp nanorods can be expected to become
recognized as an excellent inorganic material for the porous scaffolds used in
repairing bone and related applications.
PMID- 28415518
TI - Antimicrobial property, cytocompatibility and corrosion resistance of Zn-doped
ZrO2/TiO2 coatings on Ti6Al4V implants.
AB - Zn-doped ZrO2/TiO2 porous coatings (Zn-ZrO2/TiO2) were prepared on the surface of
titanium alloy (Ti6Al4V) by a hybrid approach of magnetron sputtering and micro
arc oxidation (MAO). The microstructures, phase constituents and elemental states
of the coating were investigated by scanning electron microscope (SEM) equipped
with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and X-ray
photoelectron spectroscopy (XPS). The results demonstrate that the Zn-ZrO2/TiO2
coatings are porous and its thickness is approximately 13MUm. The major phases in
the oxidation coating are tetragonal ZrO2 (t-ZrO2), cubic ZrO2 (c-ZrO2) and
rutile TiO2. XPS result reveals that Zn exists as ZnO in the Zn-ZrO2/TiO2
coatings. The biological experiments indicate that Zn-ZrO2/TiO2 coatings exhibit
not only excellent antibacterial property against Gram-positive Staphylococcus
aureus (S. aureus), but also favorable cytocompatibility. In addition, the
corrosion resistance of the coating is also appreciably improved in the simulated
body fluids (SBF), which can ensure better biocompatibility in body fluids.
PMID- 28415519
TI - Fabrication of thermal sensitive folic acid based supramolecular hybrid gels for
injectable drug release gels.
AB - Thermal sensitive supramolecular hybrid gels for injectable drug release were
prepared by adding different amounts of agar into folic acid (FA) gelator. The
gelation temperature was modulated in order to form injectable gel with body
temperature (37 degrees C). Such kind of folic acid-agar (FAG) hybrid gel makes
it possible to use supramolecular gel as injectable drug loaded gels for drug
release. FT-IR and UV-vis spectra indicate that agar macromolecules involve in
the self-assembly process through intermolecular H-bonding and pi-pi stacking
interactions with FA molecules. The SEM and TEM images demonstrate that the fiber
diameter of FAG hybrid gel is about 20nm, much smaller than that of FA gel
(40nm). However, FAG hybrid has a denser nano-fibrous network structure than FA
gels. Moreover, FAG hybrid gel is endowed with a more ordered network structure
and a little better crystallization capability by adding agar. FAG hybrid gel
also shows a shear-thinning behavior but the shear viscosity is about 2 times
higher than that of FA gel. Compared with FA gel, the storage (G') and loss (G")
moduli of the FAG gel are higher, which implies an enhanced gel strength. At the
same time, both FA and FAG gels are facilely affected by some external factors
such as acid, base and salts. In acidic or basic conditions, the strength became
weak and the gelation temperature (Tg) decreased. While, within certain
concentrations, the salt (NaCl) increased the gel strength and Tg. FAG gel
suffered lower mass loss and owned better stability in different pH solutions
compared with pure FA gel. The release behavior of the FA and injectable FAG gels
was investigated by using Rhodamine B as a mimic model drug. FAG hybrid gel shows
a long release profile and the release time is 3 times longer than that of FA
gel, up to 30h, and the accumulative release amount reaches about 86%. So it is a
potential injectable gel for sustained release drug delivery system.
PMID- 28415520
TI - Tuneable hydrolytic degradation of poly(l-lactide) scaffolds triggered by ZnO
nanoparticles.
AB - In this work we fabricate porous PLLA and PLLA/ZnO scaffolds with porosities
ranging from 10 to 90% and average pore diameter of 125-250MUm by solvent
casting/particulate leaching method. The structural evolution of PLLA/ZnO
scaffolds during their in vitro degradation in phosphate buffered saline (PBS) at
physiological pH (7.4) has been studied as a function of porosity and obtained
results were compared to plain PLLA scaffolds. The changes induced upon the
hydrolytic degradation of scaffolds have been explored by measuring the pH
changes of the medium, the mass loss, thermal transitions, crystalline structure,
thermal stability and the morphological changes. It is shown that the degradation
profile of scaffolds could be successfully modified by tuning both the amount of
ZnO nanoparticles and by varying the scaffold porosity. Results reveal that the
water dissociated on ZnO nanoparticle surfaces initiate hydrolytic degradation
reactions by reducing the strength of the chemical bonds of the adjacent PLLA
chains, causing them to further divide into water-soluble oligomers. Obtained
results may be useful towards the development of antibacterial porous structures
with tuneable degradation rates to be used as a substrate for the growth of
different kind of cells and tissues.
PMID- 28415521
TI - Effect of halloysite nanotubes on the structure and function of important
multiple blood components.
AB - Many researchers have investigated the application of halloysite nanotubes (HNTs)
in biomedicine, because of their special nanoscale hollow tubular structure.
Although the cytocompatibility of HNTs has been studied, their blood
compatibility has not been systematically investigated. In this work, the effect
of HNTs on the structure and function of different blood components has been
studied, including the morphology and hemolysis of red blood cells (RBCs). Based
on scanning electron microscopy (SEM) observations, optical density test and flow
cytometry analysis, we found that HNTs can affect the morphology and membrane
integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way.
In particular, based on UV-vis absorption spectra, fluorescence spectra and
circular dichroism (CD) spectra, HNTs can alter the secondary structure and
conformation of human fibrinogen and gamma-globulins. In addition, the detection
of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger
complement activation. In the blood clotting assay, HNTs were found to
significantly prolong the activated partial thromboplastin time (APTT), shorten
the prothrombin time (PT) of platelet-poor plasma (PPP), and change the
thromboelastography (TEG) parameters of whole blood coagulation. Furthermore,
confocal laser scanning microscopy and flow cytometry analysis were used to test
intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW
264.7 was found to be content-dependent, but not time-dependent. These findings
provide insight for the potential use of HNTs as biofriendly nanocontainers for
biomaterials in vivo.
PMID- 28415522
TI - Biocompatible nanocomposite scaffolds based on copolymer-grafted chitosan for
bone tissue engineering with drug delivery capability.
AB - Significant efforts have been made to develop a suitable biocompatible scaffold
for bone tissue engineering. In this work, a chitosan-graft-poly(acrylic acid-co
acrylamide)/hydroxyapatite nanocomposite scaffold was synthesized through a novel
multi-step route. The prepared scaffolds were characterized for crystallinity,
morphology, elemental analysis, chemical bonds, and pores size in their
structure. The mechanical properties (i.e. compressive strength and elastic
modulus) of the scaffolds were examined. Further, the biocompatibility of
scaffolds was determined by MTT assays on HUGU cells. The result of cell culture
experiments demonstrated that the prepared scaffolds have good cytocompatibility
without any cytotoxicity, and with the incorporation of hydroxyapatite in their
structure improves cell viability and proliferation. Finally, celecoxib as a
model drug was efficiently loaded into the prepared scaffolds because of the
large specific surface area. The in vitro release of the drug displayed a
biphasic pattern with a low initial burst and a sustained release of up to
14days. Furthermore, different release kinetic models were employed for the
description of the release process. The results suggested that the prepared
cytocompatible and non-toxic nanocomposite scaffolds might be efficient implants
and drug carriers in bone-tissue engineering.
PMID- 28415523
TI - Simultaneous voltammetric analysis of anti-ulcer and D2-antagonist agents in
binary mixture using redox sensor and their determination in human serum.
AB - Pencil graphite electrode was successfully modified with a thin film of poly
(eriochrome black T) and applied for the sensitive and selective voltammetric
simultaneous determination of pantoprazole sodium and domperidone in a binary
mixture. The preparation and basic electrochemical behavior of poly (eriochrome
black T) film on the Pencil graphite electrode were investigated. The modified
electrode has exhibited very high electro-catalytic activity towards the cited
mixture. The anodic peaks of the both species were well defined with enhanced
oxidation peak currents. Under the optimum conditions, the linearity ranges were
0.4-55*10-7M and 0.1-34*10-7M for pantoprazole sodium and domperidone,
respectively with detection limits of 0.12*10-7M and 0.04*10-7M for pantoprazole
sodium and domperidone, respectively. The proposed sensor has been successfully
applied in the analysis of pantoprazole sodium and domperidone in synthetic
binary mixtures and human serum.
PMID- 28415524
TI - Biomolecule-assisted synthesis of Ag/reduced graphene oxide nanocomposite with
excellent electrocatalytic and antibacterial performance.
AB - In this work, an environmentally friendly method was applied for the synthesis of
aqueous suspension of l-cysteine modified Ag nanoparticles (NPs)-decorated
reduced graphene oxide (rGO) nanocomposite. l-cysteine played a triple role as
reducing agent, stabilizer and linker of Ag NPs onto the surface of rGO. The
resultant nanocomposite was characterized by Fourier transform infrared
spectroscopy (FT-IR), X-ray diffraction studies (XRD), zeta potential, Raman
spectroscopy, scanning electron microscopy (SEM) and energy dispersive analysis
of X-ray (EDX). Meanwhile, minimum inhibitory concentration (MIC), minimum
bacterial concentration (MBC), agar well diffusion and cyclic voltammetry (CV)
techniques were used for the investigation of antibacterial and electrocatalytic
behaviors of the nanocomposite, respectively. The obtained nanocomposite showed
not only enhanced electrocatalytic activity for glucose but also excellent
antibacterial activity against Escherichia coli (E. coli) and Staphylococcus
aureus (S. aureus).
PMID- 28415525
TI - Mechanical, thermal and morphological characterisation of 3D porous Pennisetum
purpureum/PLA biocomposites scaffold.
AB - The mechanical, thermal, and morphological properties of a 3D porous Pennisetum
purpureum (PP)/polylactic acid (PLA) based scaffold were investigated. In this
study, a scaffold containing P. purpureum and PLA was produced using the solvent
casting and particulate leaching method. P. purpureum fibre, also locally known
as Napier grass, is composed of 46% cellulose, 34% hemicellulose, and 20% lignin.
PLA composites with various P. purpureum contents (10%, 20%, and 30%) were
prepared and subsequently characterised. The morphologies, structures and thermal
behaviours of the prepared composite scaffolds were characterised using field
emission scanning electron microscopy (FESEM), Fourier transform infrared
spectroscopy (FTIR), and thermogravimetric analysis (TGA). The morphology was
studied using FESEM; the scaffold possessed 70-200MUm-sized pores with a high
level of interconnectivity. The moisture content and mechanical properties of the
developed porous scaffolds were further characterised. The P. purpureum/PLA
scaffold had a greater porosity factor (99%) and compression modulus (5.25MPa)
than those of the pure PLA scaffold (1.73MPa). From the results, it can be
concluded that the properties of the highly porous P. purpureum/PLA scaffold
developed in this study can be controlled and optimised. This can be used to
facilitate the construction of implantable tissue-engineered cartilage.
PMID- 28415526
TI - Effect of variable aminoalkyl chains on chemical grafting of cellulose nanofiber
and their antimicrobial activity.
AB - Recent focus on the preparation of antimicrobial surfaces using cellulose
nanofibers (CNF) has gained considerable attention. In this work,
functionalization of CNF films in 100% aqueous solution with three different
aminosilanes, including 3-aminopropyl trimethoxysilane (APMS), 2-aminoethyl 3
aminopropyl trimethoxysilane (DAMS)and 3-2-(2-aminoethylamino) ethylamino propyl
trimethoxysilane (TAMS) is reported for the fabrication of contact active
antimicrobial materials. Grafted CNF films were comprehensively characterized by
FTIR, TGA, contact angle, elemental analysis, solid-state 29Si NMR, FEG-SEM and
SEM-EDX. It was found that all the silanes were grafted on the surface of
nanofibers without any change in the morphology or fibril structure through
different grafting efficiency, depending on the aminoalkyl chain length. The
effect of variable aminoalkyl length and initial grafting concentration was
analyzed against gram-positive (Bacillus subtilis and Staphylococcus aureus) and
Gram-negative bacteria (Escherichia coli) by qualitative and quantitative
standards. The most promising results were obtained with 3-2-(2-aminoethylamino)
ethylamino propyl-trimethoxysilane at very low concentration which completely
restrict bacterial growth after 24h with Gram-positive bacteria. This study, for
the first time, established the relationship between the aminoalkyl chain length
and its corresponding antibacterial activity.
PMID- 28415527
TI - Influence of processing parameters on the macroscopic mechanical behavior of PVA
hydrogels.
AB - This paper investigates the influence of three different processing parameters on
the global mechanical behavior of PVA (Polyvinyl alcohol)/DMSO
(Dimethylsulfoxide) hydrogels: the initial concentration of PVA, the DMSO:H2O
ratio and the number of freeze/thaw cycle applied to the material. A specific
thermo-regulated testing apparatus for hydrophilic materials is presented, along
with the performed cyclic and rupture tests. The observed mechanical responses
are explained by an in-depth analysis of the cross-linking phenomenon. Using the
Neo-Hookean hyperelastic model, the experimental data is fitted and a link
between the density of macro-molecular chains in the material and its mechanical
behavior is established. Strong differences are observed and discussed.
PMID- 28415528
TI - Improved biotribological properties of PEEK by photo-induced graft polymerization
of acrylic acid.
AB - The keys of biomaterials application in artificial joints are good hydrophilicity
and wear resistance. One kind of the potential bio-implant materials is
polyetheretherketone (PEEK), which has some excellent properties such as non
toxic and good biocompatibility. However, its bioinert surface and inherent
chemical inertness hinder its application. In this study, we reported an
efficient method for improving the surface wettability and wear resistance for
PEEK, a layer of acrylic acid (AA) polymer brushes on PEEK surface was prepared
by UV-initiated graft polymerization. The effects of different grafting
parameters (UV-irradiation time/AA monomer solution concentration) on surface
characteristics were clearly investigated, and the AA-g-PEEK specimens were
examined by ATR-FTIR, static water contact angle measurements and friction tests.
Our results reveal that AA can be successfully grafted onto the PEEK surface
after UV irradiation, the water wettability and tribological properties of AA-g
PEEK are much better than untreated PEEK because that AA is a hydrophilic
monomer, the AA layer on PEEK surface can improve its bearing capacity and reduce
abrasion. This detailed understanding of the grafting parameters allows us to
accurately control the experimental products, and this method of surface
modification broadens the use of PEEK in orthopedic implants.
PMID- 28415529
TI - A sensitive voltammetric detection of pramipexole based on 1,1,3,3
tetramethyldisilazanecarbon nanotube modified electrode.
AB - A simple low-cost method is proposed to fabricate a functionalized multi-wall
carbon nanotube (MWCNT) with 1,1,3,3-tetramethyldisilazane (TMDS) molecule. The
techniques of scanning electron microscope (SEM) with electron diffraction and
energy dispersive X-ray (EDAX) analysis were applied to characterize the
functionalized TMDS-MWCNT. The results showed that a MWCNT with high
functionalization of TMDS can be obtained using this simple method. A new
nanostructure sensor was constructed based on a glassy carbon electrode modified
with TMDS-MWCNT (TMDS-MWCNT/GCE). It was found that the TMDS-MWCNT/GCE exhibits
good catalytic activity toward oxidation of pramipexole (PPX) drug, leading to a
concentration range of 0.8 to 600MUM with a detection limit of 0.2MUM at 3sigma
using the differential pulse voltammetry technique, a sensitivity of 0.084MUAMUM
1, and a correlation coefficient of 0.991. Furthermore, the TMDS-MWCNT/GCE was
used for PPX detection in tablets and human blood serum samples. The method
showed no interference from tablet excipients; hence, it can be useful and fit
for the quantification of PPX in bulk and tablet dosage forms. The proposed
method was validated successfully as applied to the quantification of the drug in
tablet dosage forms. The accuracy of detection results using the proposed method
was evaluated as excellent comparing with those obtained by the reference method.
PMID- 28415530
TI - Poly(vinylidene difluoride)/poly(tetrafluoroethylene-co-vinylpyrrolidone) blend
membranes with antifouling properties.
AB - To inhibit fouling phenomenon in membrane process, a new amphiphilic copolymer,
poly(tetrafluoroethylene-co-vinylpyrrolidone) (P(TFE-VP)), was blended with
poly(vinylidene difluoride) (PVDF) to fabricate a series of antifouling membranes
via non solvent induced phase separation (NIPS) method. The effect of copolymer
blend ratios and TFE/VP ratios on membrane properties were evaluated, and the
stability of P(TFE-VP) in PVDF membrane was studied. The membrane morphology was
controlled by adjusting polymer concentration in dope solution, such that all
membranes have similar pore size and density, as well as pure water permeability.
In evaluating the effect of TFE/VP ratios, the content of VP in dope solutions
was also adjusted to allow a fair comparison. We found that for P(TFE-VP) with a
higher VP content, adsorption of BSA on polymer film was negligible. Higher blend
ratios of this copolymer resulted in higher surface VP content and better
hydrophilicity, but antifouling performance ceased to improve when blend ratio
was larger than 1:9 (copolymer:PVDF). Meanwhile, a lower VP content in copolymer
resulted in inferior hydrophilicity and severe fouling of the blend membranes. It
was also proved that comparing with PVP homopolymer, P(TFE-VP) had satisfying
stability inside PVDF membrane.
PMID- 28415531
TI - New synthesis of poly ortho-methoxyaniline nanostructures and its application to
construct modified multi-wall carbon nanotube/graphite paste electrode for
simultaneous determination of uric acid and folic acid.
AB - Uric acid (UA) and folic acid (FA) are compounds of biomedical interest. In
humans, about 70% of daily uric acid disposal occurs via the kidneys, and in 5
25% of humans, impaired renal (kidney) excretion leads to hyperuricemia. Folate
is another form folic acid of which is known as, is one of the B vitamins. It is
used as a supplement by women to prevent neural tube defects developing during
pregnancy. Polyortho-methoxyaniline nanostructures (POMANS) was synthesized with
a new two phase (organic-water) synthesis method. The POMANS was characterized
using transmission electron microscopy (TEM) and Fourier transform IR (FTIR).
This polymer was used to construct a modified multi-wall carbon nanotube,
graphite paste electrode (POMANS-MWCNT/GPE). Linear sweep voltammograms (LSV),
cyclic voltammetry (CV) and chronoamperometry were used to investigate the
suitability of polyortho-methoxyaniline with multi-wall carbon nanotubes paste
electrode as a modifier for the electrocatalytic oxidation of UA and FA in
aqueous solutions with various pHs. The results showed that POMANS-MWCNT/GPE had
high anodic peak currents for the electrooxidation of UA and FA in pH6.0.Under
the optimized conditions, The catalytic peak currents obtained, was linearly
dependent on the UA and FA concentrations in the range of 0.6-52 and 0.5-68MUM
with two segments and the detection limits 0.157 and 0.113MUM for UA and FA were,
respectively. Finally, the proposed method was also examined as a sensitive,
simple and inexpensive electrochemical sensor for the simultaneous determination
of UA and FA in real samples such as urine and serum.
PMID- 28415532
TI - Preparation of micro-porous bioceramic containing silicon-substituted
hydroxyapatite and beta-tricalcium phosphate.
AB - Dimensional instability caused by sintering shrinkage is an inevitable drawback
for conventional processing of hydroxyapatite (HA). A new preparation method for
biphasic calcium phosphates was developed to increase micro pores and
biodegradation without significant dimensional change. Powder pressed HA discs,
under 100MPa, were immersed in a colloidal mixture of tetraethoxysilane (TEOS)
and ammonium hydroxide for 10min, followed by drying, and then were sintered at
900 degrees C, 1050 degrees C, and 1200 degrees C, respectively. Comparing with
pure HA discs, the newly prepared product sintered up to 1200 degrees C contained
silicon substituted HA, beta-tricalcium phosphate, and calcium silicate with
better micro-porosity, high specific surface area, less sintering shrinkage and
the strength maintained. The cytocompatibility test demonstrated a better
viability for D1 mice stem cells cultured on TEOS treated HA for 14days compared
to the pure HA. This simple TEOS sol-gel pretreatment has the potential to be
applied to any existing manufacturing process of HA scaffold for better control
of sintering shrinkage, create micropores, and increase biodegradation.
PMID- 28415533
TI - Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS
hybrid composite for bone tissue engineering applications.
AB - The bioactivity and mechanical properties of hybrid composites of hydroxyapatite
(HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are
investigated, first time, for regeneration and repair of the bone tissues. HA is
synthesized to obtain the spherically shaped nanoparticles in the size range of
60+/-20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in
TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and
interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron
microscope shows the uniform dispersion of HA<=10wt% in TOPAS and at higher
concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable
mechanical properties are achieved as the compressive modulus and strength are
increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa,
respectively. Such increase in the mechanical properties of TOPAS is attributed
to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing
to better dispersion and interfacial interactions. In comparison to neat TOPAS,
hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation
significantly. The cell density and proliferation of TOPAS/HA hybrid composites
is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts
cells. Moreover, the morphology of cells changed from spherical to flattened
spread morphology demonstrating clearly the migration of the cells for the
formation of interconnected cellular network. Additionally, very few dead cells
are found in hybrid composites showing their cytocompatibility. Overall, the
hybrid composites of TOPAS/HA exhibited superior strength and stiffness along
with enhanced cytocompatibility for bone tissue engineering applications.
PMID- 28415534
TI - Influence of Si substitution on the reactivity of alpha-tricalcium phosphate.
AB - Silicon substituted calcium phosphates have been widely studied over the last ten
years due to their enhanced osteogenic properties. Notwithstanding, the role of
silicon on alpha-TCP reactivity is not clear yet. Therefore, the aim of this work
was to evaluate the reactivity and the properties of Si-alpha-TCP in comparison
to alpha-TCP. Precursor powders have similar properties regarding purity,
particle size distribution and specific surface area, which allowed a better
comparison of the Si effects on their reactivity and cements properties. Both Si
alpha-TCP and alpha-TCP hydrolyzed to a calcium-deficient hydroxyapatite when
mixed with water but their conversion rates were different. Si-alpha-TCP
exhibited a slower setting rate than alpha-TCP, i.e. kSSA for Si-TCP (0.021g.m
2.h-1) was almost four times lower than for alpha-TCP (0.072g.m-2.h-1). On the
other hand, the compressive strength of the CPC resulting from fully reacted Si
alpha-TCP was significantly higher (12.80+/-0.38MPa) than that of alpha-TCP
(11.44+/-0.54MPa), due to the smaller size of the entangled precipitated apatite
crystals.
PMID- 28415535
TI - Study on montmorillonite/insulin/TiO2 hybrid nanocomposite as a new oral drug
delivery system.
AB - This study was conducted in two main stages. In the first stage, drug-loaded
montmorillonite nanocomposites were prepared by intercalation of insulin into the
montmorillonite layers in acidic deionized (DI) water. In the second stage, to
increase the release of insulin from the prepared nanocomposites they were coated
with TiO2, an inorganic porous coating, by using titanium (IV) butoxide, as
precursor. The prepared nanocomposites were characterized by FT-IR, XRD, FE-SEM,
BET, DLS and Zeta potential analysis. After investigating the release behaviour
of the nanocomposites by UV-Vis absorbance technique, the results revealed that
incorporation of porous TiO2 coating increased the drug entrapment noticeably,
and decreased the amount of drug release, so that nanocomposites without and with
TiO2 coating released the drug after 60min and 22h in pH7.4, respectively. These
results could be used in converting the insulin utilization from injection to
oral.
PMID- 28415536
TI - Template-etching route to construct uniform rattle-type Fe3O4@SiO2 hollow
microspheres as drug carrier.
AB - Template-etching strategy was put forward to synthesize rattle-type magnetic
silica (Fe3O4@SiO2) hollow microspheres in a controlled way. During the
experiment, monodisperse Fe2O3 microspheres were fabricated as physical template
to generate uniform Fe2O3@SiO2 with controlled shell thicknesses through sol-gel
method, and the subsequent Fe2O3 template etching process created variable space
between Fe2O3 core and SiO2 shell, and the final calcination process transformed
rattle-type Fe2O3@SiO2 hollow microspheres into corresponding Fe3O4@SiO2 product
in hydrogen/nitrogen atmosphere. Compared with traditional physical template,
here template-etching synthesis of rattle-type hollow microspheres saved the
insertion of middle shells and their removal, which simplified the synthesis
process with controllable core size and shell thickness. The rattle-type
Fe3O4@SiO2 hollow microspheres as drug carrier show efficient doxorubicin (DOX)
loading, and the release rate of DOX loaded the rattle-type Fe3O4@SiO2 hollow
microspheres exhibit a surprising shell-thickness-dependent and a pH responsive
drug release features. Additionally, MTT assays in HeLa cells demonstrated that
the Fe3O4@SiO2 nanocarriers were non-toxic even at the concentration of 250ugmL-1
for 48h. Thus, our results revealed that the Fe3O4@SiO2-DOX could play an
important role in the development of intracellular delivery nanodevices for
cancer therapy.
PMID- 28415537
TI - Potassium-doped mesoporous bioactive glass: Synthesis, characterization and
evaluation of biomedical properties.
AB - A bifunctional mesoporous bioactive glass (MBG) with composition
(49SiO2.20CaO.20Na2O.7K2O.4P2O5 mol%) was synthesized by a facile sol-gel method,
using polyethylene glycol (PEG 6000) as a soft template. The structure,
morphology (spherical with approximate size 1MUm) and composition of MBG were
determined by fourier transform infrared spectroscopy, the scanning electron
microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX), respectively.
The surface area (189.53m2g-1 with the pore size of 21nm) of MBG was measured by
Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analysis. The
formation of hydroxyapatite (HAp) layer on the glass surface upon immersion in
simulated body fluid (SBF) was monitored through X-ray diffraction (XRD) which
indicates enhanced bioactivity as compared to previous studies. The animals
study, protein adsorption ability, and cytotoxicity investigations show no tissue
damage, good biomedical properties and no encumbrance with cell cycle (even at a
concentration of 80MUg/mL). Moreover, the cell proliferation analysis reveals the
non-toxic property of MBG at a concentration of 20MUg/mL. Notably, a cumulative
drug (ciprofloxacin, an antibiotic) release of 75% was observed for first 48h and
the further release of 90% was observed over a period of two weeks. The
synthesized MBG also shows osteoblast activity and bone mineralization as
revealed by alkaline phosphatase activity (ALP) and osteocalcin formation.
PMID- 28415538
TI - Fabrication of polypropylene/silver nanocomposites for biocidal applications.
AB - This paper presents a study on biocidal effect of polymer nanocomposite films of
gamma irradiated polypropylene (PP) and silver nanoparticles. The modified
polypropylene was obtained from isotactic polypropylene (iPP) in pellets form by
irradiation with gamma rays in the presence of acetylene. A new morphology with
long chain branching of PP and distinct rheology is obtained by this process. The
blend of 50/50wt% neat PP and PP modified by gamma radiation were further mixed
using a twin screw extruder. The AgNPs were infused into this polymer blend at
different concentrations of: 0.1%; 0.25%; 0.5%; 1.0%; 1.0% (PVP), 2.0% and 4.0%
by wt%. These polymer nanocomposites were characterized by Raman spectroscopy,
scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS),
thermogravimetric analysis (TG), differential scanning calorimetry (DSC), X-ray
diffraction (XRD), transmission electron microscopy (TEM), cytotoxicity test and
Kirby-Bauer disk diffusion techniques. The bactericidal effect of Pseudomonas
aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) were assessed in
detail.
PMID- 28415539
TI - In vitro cytotoxicity evaluation of nano-carbon particles with different sp2/sp3
ratios.
AB - Graphitization occurs during the long-term service of a diamond-like carbon (DLC)
modified artificial joint. Then, DLC wear debris, which are carbon particles with
different sp2/sp3 ratios and sizes ranging from the nano- to micro-meter scale
produced. In this paper, to promote the application of DLC coating for artificial
joint modification, the cytotoxicity of DLC debris (nano-carbon particles, NCs)
with different sp2/sp3 ratios was studied. The microstructure and physical
characteristics of NCs with different sp2/sp3 ratios were investigated by Raman
spectroscopy, X-ray photoelectron spectroscopy (XPS), Transmission Electron
Microscope (TEM) and Dynamic Light Scattering (DLS). Meanwhile, osteoblasts and
macrophages were applied to characterize the cytotoxicity of the NCs. In vitro
cytotoxicity assay results indicated that cells incubated with NCs of different
sp2/sp3 ratios had greater osteogenic capacity, and these particles caused a
weaker immune response in comparison with CoCrMo particles. Taken together, the
results indicated that NCs with different sp2/sp3 ratios presented a good
cytocompatibility than CoCrMo particles. But no significant differences were
observed among NCs with different sp2/sp3 ratios. The better cytocompatibility of
NCs is mainly attributable to their surface charge.
PMID- 28415540
TI - Biocompatible magnetite nanoparticles synthesized by one-pot reaction with a cell
membrane mimetic copolymer.
AB - In this paper, a series of random copolymers poly(methacrylic acid -co-2
methacryloyloxyethyl phosphorylcholine) P(MAA-co-MPC) were synthesized firstly
via RAFT living polymerization. The P(MAA-co-MPC) copolymer side chains bear cell
membrane phosphorylcholine zwitterions to endow biocompatibility and carboxylic
groups to confer coordination with metal ions. Thus, the copolymer was adopted to
modify Fe3O4 nanoparticle by a one-pot coprecipitation approach. The effects of
the copolymer composition as well as the ratio between the copolymers and iron
ions on the performances of the magnetite nanoparticles were researched. The
diameters of the nanoparticles could be easily tuned by changing the initial
copolymer amount. Moreover, a long-term colloidal stability of magnetite
particles was obtained after P(MAA-co-MPC) modification. Biocompatibility of the
P(MAA-co-MPC) copolymer coated magnetite nanoparticles was investigated by
protein adsorption, in vitro cytotoxicity and cell uptake studies. It was found
that the copolymer content of magnetite nanoparticles correlates with its
biocompatibility. Excellent biocompatibility could be obtained when the content
of the copolymer in the composite nanoparticles reached to 54%.
PMID- 28415541
TI - Synthesis, characterization of CaF2 doped silicate glass-ceramics.
AB - This paper reports the fabrication and characterization of silicate glass
ceramics doped with (0-12mol%) CaF2. TGA-DSC analysis was carried out to
determine the crystallization temperature and stability of glass measured by two
glass parameters; Hruby parameter KH=(Tx-Tg)/(TL-Tx) and Weinberg parameter
KW=(Tc-Tg)/TL. It was found that with CaF2 doping improved sinterability at low
temperature and provided stability to the glass. The XRD pattern exhibits a
single phase of combeite and doping of CaF2 cause increase in crystallite size.
Microstructure of samples was also improved with CaF2 addition, pores were
significantly reduced. After 15days immersion in simulated body fluid all samples
developed apatite layer onto its surface. Hence, the addition of CaF2 provided
bioactive glass-ceramic material having a low processing temperature.
PMID- 28415542
TI - Bladder smooth muscle cells on electrospun poly(epsilon-caprolactone)/poly(l
lactic acid) scaffold promote bladder regeneration in a canine model.
AB - Engineering of urinary bladder has been the focus of numerous studies in recent
decade. Novel biomaterials, innovative fabrication methods and various
modification processes of scaffolds are the critical issues to find supportive
matrices. Supportive characteristics of electrospun PCL/PLLA nano-scaffold for
bladder augmentation in canine model and the role of bladder cells in
regeneration process were appraised. Electrospun PCL/PLLA was fabricated by co
electrospinning of PCL and PLLA. Bladder cells were isolated and transduced with
lentiviral particles encoding eGFP and JRed proteins. Electrospun PCL/PLLA was
seeded with different bladder cells individually or in co-culture condition. Cell
free and cell-seeded electrospun PCL/PLLA scaffolds (10cm2) were surgically
implanted in bladders of eight female dogs for three months. To evaluate bladder
regeneration, the dogs were sacrificed and their bladders were examined
macroscopically and microscopically for presence of tracking proteins, expression
of cell-specific markers and histological attributes of regenerated tissues. All
animals survived the experiment with no complication. In smooth muscle
transplanted group complete regeneration and covering of scaffold were observed.
Other groups revealed partial regeneration. A well-developed layer of urothelium
was formed in all groups in regenerated parts. Smooth muscle transplanted group
showed the most developed muscle layer. Regenerated tissue demonstrated typical
expression of cell-specific markers. No expression of eGFP and JRed was observed.
Electrospun PCL/PLLA scaffold with proper handling, suture retention, nano-sized
surface features, maintenance of normal phenotype of cells and minimal adverse
effects in body can be a supportive substrate for bladder wall regeneration when
seeded with bladder smooth muscle cells.
PMID- 28415543
TI - Facile synthesis of a silver nanoparticles/polypyrrole nanocomposite for non
enzymatic glucose determination.
AB - The present work describes the synthesis of a new conductive nanocomposite based
on polypyrrole (PPy) and silver nanoparticles (PPy-AgNP) based on a facile
reverse microemulsion method and its application as a non-enzymatic
electrochemical sensor for glucose detection. Focusing on the best sensor
performance, all experimental parameters used in the synthesis of nanocomposite
were optimized based on its electrochemical response for glucose.
Characterization of the optimized material by FT-IR, cyclic voltammetry, and DRX
measurements and TEM images showed good monodispersion of semispherical Ag
nanoparticles capped by PPy structure, with size average of 12+/-5nm. Under the
best analytical conditions, the proposed sensor exhibited glucose response in
linear dynamic range of 25 to 2500MUmolL-1, with limit of detection of 3.6MUmolL
1. Recovery studies with human saliva samples varying from 99 to 105% revealed
the accuracy and feasibility of a non-enzymatic electrochemical sensor for
glucose determination by easy construction and low-cost.
PMID- 28415545
TI - Engineering bone regeneration with novel cell-laden hydrogel microfiber
injectable calcium phosphate scaffold.
AB - Cell-based tissue engineering is promising to create living functional tissues
for bone regeneration. The implanted cells should be evenly distributed in the
scaffold, be fast-released to the defect and maintain high viability in order to
actively participate in the regenerative process. Herein, we report an injectable
calcium phosphate cement (CPC) scaffold containing cell-encapsulating hydrogel
microfibers with desirable degradability that could deliver cells in a timely
manner and maintain cell viability. Microfibers were synthesized using partially
oxidized alginate with various concentrations (0-0.8%) of fibrinogen to optimize
the degradation rate of the alginate-fibrin microfibers (Alg-Fb MF). A fibrin
concentration of 0.4% in Alg-Fb MF resulted in the greatest enhancement of cell
migration, release and proliferation. Interestingly, a significant amount of cell
cell contact along the long-axis of the microfibers was established in Alg-0.4%Fb
MF as early as day 2. The injectable tissue engineered construct for bone
reconstruct was fabricated by mixing the fast-degradable Alg-0.4%Fb MF with CPC
paste at 1:1 volume ratio. In vitro study showed that cells re-collected from the
construct maintained good viability and osteogenic potentials. In vivo study
demonstrated that the hBMSC-encapsulated CPC-MF tissue engineered construct
displayed a robust capacity for bone regeneration. At 12weeks after implantation,
osseous bridge in the rat mandibular defect was observed in CPC-MF-hBMSCs group
with a new bone area fraction of (42.1+/-7.8) % in the defects, which was >3-fold
that of the control group. The novel tissue-engineered construct presents an
excellent prospect for a wide range of dental, craniofacial and orthopedic
applications.
PMID- 28415544
TI - beta-pyrophosphate: A potential biomaterial for dental applications.
AB - Tooth hypersensitivity is a growing problem affecting both the young and ageing
population worldwide. Since an effective and permanent solution is not yet
available, we propose a new methodology for the restoration of dental enamel
using femtosecond lasers and novel calcium phosphate biomaterials. During this
procedure the irradiated mineral transforms into a densified layer of acid
resistant iron doped beta-pyrophosphate, bonded with the surface of eroded
enamel. Our aim therefore is to evaluate this densified mineral as a potential
replacement material for dental hard tissue. To this end, we have tested the
hardness of beta-pyrophosphate pellets (sintered at 1000 degrees C) and its
mineral precursor (brushite), the wear rate during simulated tooth-brushing
trials and the cytocompatibility of these minerals in powder form. It was found
that the hardness of the beta-pyrophosphate pellets is comparable with that of
dental enamel and significantly higher than dentine while, the brushing trials
prove that the wear rate of beta-pyrophosphate is much slower than that of
natural enamel. Finally, cytotoxicity and genotoxicity tests suggest that iron
doped beta-pyrophosphate is cytocompatible and therefore could be used in dental
applications. Taken together and with the previously reported results on laser
irradiation of these materials we conclude that iron doped beta-pyrophosphate may
be a promising material for restoring acid eroded and worn enamel.
PMID- 28415546
TI - Effect of nano/micro-Ag compound particles on the bio-corrosion, antibacterial
properties and cell biocompatibility of Ti-Ag alloys.
AB - In this research, Ti-Ag alloys were prepared by powder metallurgy, casting and
heat treatment method in order to investigate the effect of Ag compound particles
on the bio-corrosion, the antibacterial property and the cell biocompatibility.
Ti-Ag alloys with different sizes of Ag or Ag-compounds particles were
successfully prepared: small amount of submicro-scale (100nm) Ti2Ag precipitates
with solid solution state of Ag, large amount of nano-scale (20-30nm) Ti2Ag
precipitates with small amount of solid solution state of Ag and micro-scale
lamellar Ti2Ag phases, and complete solid solution state of Ag. The mechanical
tests indicated that both nano/micro-scale Ti2Ag phases had a strong dispersion
strengthening ability and Ag had a high solid solution strengthening ability.
Electrochemical results shown the Ag content and the size of Ag particles had a
limited influence on the bio-corrosion resistance although nano-scale Ti2Ag
precipitates slightly improved corrosion resistance. It was demonstrated that the
nano Ag compounds precipitates have a significant influence on the antibacterial
properties of Ti-Ag alloys but no effect on the cell biocompatibility. It was
thought that both Ag ions release and Ti2Ag precipitates contributed to the
antibacterial ability, in which nano-scale and homogeneously distributed Ti2Ag
phases would play a key role in antibacterial process.
PMID- 28415547
TI - Effect of polymer degradation on prolonged release of paclitaxel from
filomicelles of polylactide/poly(ethylene glycol) block copolymers.
AB - Paclitaxel is one of the most efficient anticancer agents, but the conventional
dosage formulations cause many side effects. PLA-PEG filomicelles are promising
carriers of paclitaxel because high loading capacity and long term release can be
achieved. Slow release of cytostatic drugs is very advantageous due to prolonged
exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this
study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for
prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG
filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at
37 degrees C at various pH values to elucidate the influence of polymer
degradation on drug release. NMR, GPC and HPLC were used to follow polymer
degradation and drug release. The release of paclitaxel is strongly dependent on
the degradation of micelles. A biphasic drug release profile is observed for both
PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster
release in the second phase. Degradation is faster at acidic pH than at pH7.4,
and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles,
leading to various rates of drug release. The correlation between degradation and
drug release is very helpful for the development of novel drug carriers with
tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles
was evidenced, thus showing their potential as carrier of antitumor drugs.
PMID- 28415548
TI - In vitro evaluation of Ag-containing calcium phosphates: Effectiveness of Ag
incorporated beta-tricalcium phosphate.
AB - Development of bioceramics with antibacterial activity and without cytotoxicity
would be beneficial for preventing infection associated with implants. This study
aimed to capitalize on the antibacterial properties of silver (Ag) incorporated
in or coexisting in metallic form with calcium phosphates (CaPs). The in vitro
dissolution behavior, antibacterial activity, and cytotoxicity of Ag-containing
CaPs with different phase fractions of hydroxyapatite (HA) and beta-tricalcium
phosphate (beta-TCP) were evaluated. The antibacterial activity of Ag-containing
CaPs depended on the main phase of CaP, the chemical state of Ag, and the amount
of incorporated Ag. Superior antibacterial activity was obtained from sustained
release of Ag ions through continuous dissolution of Ag-incorporated beta-TCP
compared to that obtained for HA coexisting with metallic Ag particles. Ag
containing CaPs did not exhibit any toxic effect on V79 fibroblasts. Thus, these
results demonstrated the effectiveness of Ag-incorporated beta-TCP in preventing
infection, with respect to long-term applications.
PMID- 28415549
TI - The precursors effects on biomimetic hydroxyapatite ceramic powders.
AB - In this study, effects of the starting material on chemical, physical, and
biological properties of biomimetic hydroxyapatite ceramic powders (BHA) were
investigated. Characterization and chemical analysis of BHA powders were
performed by using XRD, FT-IR, and ICP-AES. Microstructural features such as size
and morphology of the resulting BHA powders were characterized by using BET, nano
particle sizer, pycnometer, and SEM. Additionally, biological properties of the
BHA ceramic powders were also investigated by using water-soluble tetrazolium
salts test (WST-1). According to the chemical analysis of BHA ceramic powders,
chemical structures of ceramics which are prepared under different conditions and
by using different starting materials show differences. Ceramic powders which are
produced at 80 degrees C are mainly composed of hydroxyapatite, dental
hydroxyapatite (contain Na and Mg elements in addition to Ca), and calcium
phosphate sulfide. However, these structures are altered at high temperatures
such as 900 degrees C depending on the features of starting materials and form
various calcium phosphate ceramics and/or their mixtures such as Na-Mg
hydroxyapatite, hydroxyapatite, Mg-Whitlockit, and chloroapatite. In vitro
cytotoxicity studies showed that amorphous ceramics produced at 80 degrees C and
ceramics containing chloroapatite structure as main or secondary phases were
found to be extremely cytotoxic. Furthermore, cell culture studies showed that
highly crystalline pure hydroxyapatite structures were extremely cytotoxic due to
their high crystallinity values. Consequently, the current study indicates that
the selection of starting materials which can be used in the production of
calcium phosphate ceramics is very important. It is possible to produce calcium
phosphate ceramics which have sufficient biocompatibility at physiological pH
values and by using appropriate starting materials.
PMID- 28415550
TI - High impact of in situ dextran coating on biocompatibility, stability and
magnetic properties of iron oxide nanoparticles.
AB - Biocompatible ferrofluids based on dextran coated iron oxide nanoparticles were
fabricated by conventional co-precipitation method. The experimental results show
that the presence of dextran in reaction medium not only causes to the appearance
of superparamagnetic behavior but also results in significant suppression in
saturation magnetization of dextran coated samples. These results can be
attributed to size reduction originated from the role of dextran as a surfactant.
Moreover, weight ratio of dextran to magnetic nanoparticles has a remarkable
influence on size and magnetic properties of nanoparticles, so that the sample
prepared with a higher weight ratio of dextran to nanoparticles has the smaller
size and saturation magnetization compare with the other samples. In addition,
the ferrofluids containing such nanoparticles have an excellent stability at
physiological pH for several months. Furthermore, the biocompatibility studies
reveal that surface modification of nanoparticles by dextran dramatically
decreases the cytotoxicity of bare nanoparticles and consequently improves their
potential application for diagnostic and therapeutic purposes.
PMID- 28415551
TI - A biodegradable AZ91 magnesium alloy coated with a thin nanostructured
hydroxyapatite for improving the corrosion resistance.
AB - The main aim of this study was to investigate the properties of an AZ91 alloy
coated with nanostructured hydroxyapatite (HA) prepared by radio frequency (RF)
magnetron sputtering. The bioactivity and biomineralization of the AZ91 magnesium
alloy coated with HA were investigated in simulated body fluid (SBF) via an in
vitro test. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR)
spectroscopy, and X-ray diffraction (XRD) analyses were performed. The samples
were immersed in SBF to study the ability of the surface to promote the formation
of an apatite layer as well as corrosion resistance and mass change of the HA
coated AZ91 alloy. Electrochemical tests were performed to estimate the corrosion
behaviour of HA-coated and uncoated samples. The results revealed the capability
of the HA coating to significantly improve the corrosion resistance of the
uncoated AZ91 alloy.
PMID- 28415552
TI - In vitro and in vivo characterization of anodised zirconium as a potential
material for biomedical applications.
AB - In vitro studies offer the insights for the understanding of the mechanisms at
the tissue-implant interface that will provide an effective functioning in vivo.
The good biocompatibility of zirconium makes a good candidate for biomedical
applications and the attractive in vivo performance is mainly due to the presence
of a protective oxide layer. The aim of this study is to evaluate by in vitro and
in vivo approach, the influence of surface modification achieved by anodisation
at 30 and 60V on zirconium implants on the first steps of the osseointegration
process. In this study cell attachment, proliferation and morphology of mouse
myoblast C2C12-GFP and in mouse osteoprogenitor MC3T3-E1 cells was evaluated.
Also, together with the immune system response, osteoclast differentiation and
morphology with RAW 264.7 murine cell line were analysed. It was found that
anodisation treatment at 60V enhanced cell spreading and the osteoblastic and
osteoclastic cells morphology, showing a strong dependence on the surface
characteristics. In vivo tests were performed in a rat femur osteotomy model.
Dynamical and static histological and histomorphometric analyses were developed
15 and 30days after surgery. Newly formed bone around Zr60V implants showed a
continuous newly compact and homogeneous bone just 15 after surgery, as judged by
the enhanced thickness and mineralization rate. The results indicate that
anodising treatment at 60V could be an effective improvement in the
osseointegration of zirconium by stimulating adhesion, proliferation, morphology,
new bone thickness and bone mineral apposition, making zirconium an emerging
candidate material for biomedical applications.
PMID- 28415553
TI - Promising silicones modified with cationic biocides for the development of
antimicrobial medical devices.
AB - We have tested silicones containing 2% or 5% of the cationic biocides
polyhexamethylene guanidine dodecylbenzenesulfonate (PHMG-DBS), 1-octyl-3
methylimidazolium tetrafluoroborate (OMIM-BF4) or 1-dodecyl-3-methylimidazolium
tetrafluoroborate (DMIM-BF4) against the major relevant bacterial and yeast
species in health care-associated infections (HCAI). Study conducted according to
the international standard ISO 22196 revealed that silicones containing 2% or 5%
DMIM-BF4 or 5% PHMG-DBS presented the highest antimicrobial activity, leading to
a logarithmic growth reduction of 3.03 to 6.46 and 3.65 to 4.85 depending on the
bacterial or fungal species. Heat-pretreated silicones containing 2% DMIM-BF4
kept a high activity, with at least a 3-log reduction in bacterial growth, except
against P. aeruginosa where there was only a 1.1-log reduction. After 33days, the
release ratio of cationic biocide from silicone films containing 5% of DMIM-BF4
was found to be 5.6% in pure water and 1.9% in physiological saline solution,
respectively. No leaching of PHMG-DBS polymeric biocide was detected under the
same conditions. These results demonstrate unambiguously that silicones
containing 2% DMIM-BF4 or 5% PHMG-DBS present high antimicrobial activity, as
well as high leaching resistance and therefore may be good candidates for the
development of safer medical devices.
PMID- 28415554
TI - Phytosynthesis of silver nanoparticles using aqueous leaf extracts of Lippia
citriodora: Antimicrobial, larvicidal and photocatalytic evaluations.
AB - Nanoscience and nanotechnology represent new and enabling platforms that promise
to provide broad range of novel and improved technologies for environmental,
biological and other scientific applications. This study reports the synthesis of
silver nanoparticles mediated by aqueous leaf extract of Lippia citriodora at two
different temperatures of 50 degrees C and 90 degrees C. The synthesis of
colloidal silver nanoparticles (AgNPs) was monitored by the use of UV-visible
spectroscopy at different temperatures and time intervals. The surface plasmon
bands (SPBs) showed peaks between 417 and 421nm at 90 degrees C and around 430nm
at 50 degrees C, indicating a red shift at lower temperature. Fourier transform
infrared (FTIR) analysis of the nanoparticles showed the presence of similar
peaks found in the spectra of the plant extract. The size of the AgNPs was
confirmed by transmission electron microscopy (TEM) which indicated an average
size of 23.8nm (90 degrees C) and 25nm (50 degrees C). The nanoparticles showed
better antimicrobial activities when compared to the crude plant extract against
several screened pathogens: Gram negative (Escherichia coli, and Salmonella
typhi) and Gram positive (Bacillus subtilis and Staphylococcus aureus) strains
and a fungi organism; Candida albicans. In addition, the AgNPs showed good
larvicidal efficacy against early 4th instar of Culex quinquefasciatus (a vector
of lymphatic filariasis). Finally, the nanoparticles exhibited photocatalytic
properties on an industrial waste pollutant, methylene blue.
PMID- 28415555
TI - Yb3+,Er3+,Eu3+-codoped YVO4 material for bioimaging with dual mode excitation.
AB - We propose an efficient bioimaging strategy using Yb3+,Er3+,Eu3+-triplet doped
YVO4 nanoparticles which were synthesized with polymer as a template. The
obtained particles possess nanoscale, uniform, and flexible excitation. The
effect of Eu3+ ions on the luminescence properties of YVO4:Yb3+,Er3+,Eu3+ was
investigated. The upconversion mechanism of the prepared material was also
discussed. The structure and optical properties of the prepared material were
characterized by using X-ray diffraction (XRD), Fourier-transform IR spectroscopy
(FTIR), scanning electron microscopy (SEM), Transmission electron microscopy
(TEM) upconversion and photoluminescence spectra. The Commission International de
I'Eclairage (CIE) chromaticity coordinates was investigated to confirm the
performance of color luminescent emission. The prepared YVO4:Yb3+,Er3+,Eu3+
nanoparticles could be easily dispersed in water by surface modification with
cysteine (Cys) and glutathione (GSH). The aqueous dispersion of the modified
YVO4:Yb3+,Er3+,Eu3+ exhibits bright upconversion and downconversion luminescence
and has been applied for bioimaging of HeLa cells. Our developed material with
dual excitation offers a promising advance in bioimaging.
PMID- 28415556
TI - Construction of Zn-incorporated multilayer films to promote osteoblasts growth
and reduce bacterial adhesion.
AB - To improve the biological performance of titanium substrates, a bioactive
multilayered structure of chitosan/gelatin pair, containing zinc ions, was
constructed via a layer-by-layer self-assembly technique. The successful
preparation of zinc ions incorporated multilayer films was demonstrated by
scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle
measurements, respectively. The biological behaviors of osteoblasts adhered to
modified Ti substrates were investigated in vitro via cytoskeleton observation,
cell viability measurement, and alkaline phosphatase activity assay. The
cytocompatibility evaluation verified that the present system was capable of
promoting the growth of osteoblasts. In addition, Gram-positive (Staphylococcus
aureus) and Gram-negative (Escherichia coli) bacteria were used to evaluate
antibacterial property of modified Ti substrates. Bacterial adhesion and
viability assay confirmed that Zn-loaded multilayer films were able to inhibit
the adhesion and growth of bacteria. The approach presented here affords an
alternative to reduce bacterial infection and promote osteoblast growth for
titanium-based implants.
PMID- 28415557
TI - Long non-coding RNA CTA sensitizes osteosarcoma cells to doxorubicin through
inhibition of autophagy.
AB - Recently, several long non-coding RNAs (lncRNAs) have been implicated in
osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy
resistance of OS still remain unclear. This study aimed to screen a novel lncRNA
that contributes to chemotherapeutic resistance of OS, and to explore the
underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated
in OS tissues compared to their matched non-tumor tissues, and low expression of
lncRNA CTA was significantly associated with the advanced clinical stage and
tumor size. In addition, OS patients with low lncRNA CTA levels showed a worse
prognosis when compared with those with high expression of lncRNA CTA.
Furthermore, we report that lncRNA CTA has an inverse relationship with miR-210
expression in OS tissues. LncRNA CTA could be activated by doxorubicin (DOX), and
could promote OS cell apoptosis by competitively binding miR-210, while inhibit
cell autophagy. On the other hand, lncRNA CTA was downregulated in DOX-resistant
OS cells. Overexpression of lncRNA CTA reduced autophagy and subsequently
overcame DOX resistance of OS in vitro and in vivo. Therefore, we demonstrate
that lncRNA CTA is an essential regulator in DOX-induced OS cell apoptosis, and
the lncRNA CTA-miR-210 axis plays an important role in reducing OS
chemoresistance.
PMID- 28415558
TI - Family with sequence similarity 13C (FAM13C) overexpression is an independent
prognostic marker in prostate cancer.
AB - FAM13C, a gene with unknown function is included in several mRNA signatures for
prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis
and its relationship to molecularly defined subsets, we analyzed FAM13C
expression by immunohistochemistry on a tissue microarray containing 12,400
prostate cancer specimens. Results were compared to phenotype, ERG status,
genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. FAM13C was
detectable in cell nuclei of cancerous and non-neoplastic prostate cells. 67.5%
of 9,633 interpretable cancers showed FAM13C expression: strong in 28.3%,
moderate in 24.6% and weak in 14.6%. Strong FAM13C expression was linked to
advanced pT stage, high Gleason grade, positive lymph node status, and early
biochemical recurrence (p < 0.0001 each). FAM13C expression was associated with
TMPRSS2:ERG fusions. It was present in 85% of ERG positive but in only 54% of ERG
negative cancers (p < 0.0001), and in 91.1% of PTEN deleted but in only 69.2% of
PTEN non-deleted cancers (p < 0.0001). The prognostic role of FAM13C expression
was independent of classical and quantitative Gleason grade, pT stage, pN stage,
surgical margin status and preoperative PSA. In conclusion, the results of our
study demonstrate that expression of FAM13C is an independent prognostic marker
in prostate cancer. Finding FAM13C also in non-neoplastic prostate tissues
highlights the importance of properly selecting cancer-rich areas for RNA-based
FAM13C expression analysis.
PMID- 28415559
TI - Transcriptome analysis reveals differentially expressed lncRNAs between oral
squamous cell carcinoma and healthy oral mucosa.
AB - Oral cavity and oropharyngeal squamous cell carcinoma (OSCC) is a major cancer
type in the head and neck region. To better understand the roles long non-coding
RNA (lncRNA) play in OSCC carcinogenesis, we compared the expression levels of
3,054 probe sets for lncRNAs between 167 OSCCs and 45 healthy oral mucosa using
an Affymetrix HG U133 plus 2.0 array dataset. We found 658 lncRNA transcripts
(790 probe sets) to be significantly differentially expressed using a criteria of
FDR < 0.01, with 36 of them (39 probe sets) showing more than a 2-fold change. We
further validated the top differentially expressed lncRNAs in three independent
datasets from Gene Expression Omnibus (GEO) repository: GSE42743, GSE9844, and
GSE6791. Fourteen lncRNAs (15 probe sets) were validated in all three datasets
using the criteria FDR < 0.01: LOC441178, C5orf66-AS1, HCG22, FLG-AS1,
CCL14/CCL15-CCL14, LOC100506990, TRIP10, PCBP1-AS1, LINC01315, LINC00478, COX10
AS1/LOC100506974, MLLT4-AS1, MIR31HG, and DUXAP10/LINC01296. Three lncRNAs in the
validated list which showed the highest fold change (LOC441178, HCG22 and C5orf66
AS1) were verified by quantitative RT-PCR in a subset of 20 OSCCs and 10 control
samples. In silico prediction of their functional role has given us directions
for further investigation.
PMID- 28415560
TI - Gallbladder papillary neoplasms share pathological features with intraductal
papillary neoplasm of the bile duct.
AB - Intraductal papillary neoplasm of the bile duct (IPNB) has been widely
recognized. However, the knowledge of intracystic papillary neoplasm of the
gallbladder (IPNG) including papillary adenoma and adenocarcinoma is not well
defined. In this study, we compared the clinicopathological and
immunohistochemical features between 32 IPNG cases and 32 IPNB cases. IPNG-1 (low
high grade dysplasia) exhibited an earlier onset age, smaller tumor size and
lower level of CK20 expression compared to IPNG-2 (invasive carcinoma).
Histologically, pancreaticobiliary and intestinal subtype accounted for nearly
half of IPNG or IPNB (44.4% and 48.1% vs. 44.0% and 44.0%), respectively.
Immunohistochemically, 88.9% of IPNG and 92.0% of IPNB cases were positive for
MUC1, and 96.3% and 92.0% for CK7, respectively. CDX2 and MUC2 were more highly
expressed in the intestinal subtype than in other subtypes. CK20 expression
increased in parallel with tumor progression. In addition, 53.1% of IPNG cases
and 68.6% of IPNB cases exhibited invasive carcinoma, and showed significant
survival advantages to conventional gallbladder adenocarcinoma and
cholangiocarcinoma, respectively. In conclusion, papillary adenoma and
adenocarcinoma of the gallbladder can be recognized as different pathological
stages of IPNG, and they share pathological features with IPNB.
PMID- 28415561
TI - Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of
gynecologic cancer stem cells through expression of HSP27.
AB - Cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) are defined by
their higher tumor-initiating ability, self-renewal capacity and differentiation
capacity. CSCs/CICs are resistant to several therapies including chemotherapy and
radiotherapy. CSCs/CICs thus are thought to be responsible for recurrence and
distant metastasis, and elucidation of the molecular mechanisms of CSCs/CICs are
essential to design CSC/CIC-targeting therapy. In this study, we analyzed the
molecular aspects of gynecological CSCs/CICs. Gynecological CSCs/CICs were
isolated as ALDH1high cell by Aldefluor assay. The gene expression profile of
CSCs/CICs revealed that several genes related to stress responses are
preferentially expressed in gynecological CSCs/CICs. Among the stress response
genes, a small heat shock protein HSP27 has a role in the maintenance of
gynecological CSCs/CICs. The upstream transcription factor of HSP27, heat shock
factior-1 (HSF1) was activated by phosphorylation at serine 326 residue (pSer326)
in CSCs/CICs, and phosphorylation at serine 326 residue is essential for
induction of HSP27. Immunohistochemical staining using clinical ovarian cancer
samples revealed that higher expressions of HSF1 pSer326 was related to poorer
prognosis. These findings indicate that activation of HSF1 at Ser326 residue and
transcription of HSP27 is related to the maintenance of gynecological CSCs/CICs.
PMID- 28415562
TI - Genome-wide association study of high-altitude pulmonary edema in a Han Chinese
population.
AB - A two-stage genome-wide association study (GWAS) was performed to identify and
analyze genes and single nucleotide polymorphisms (SNPs) associated with high
altitude pulmonary edema (HAPE) in a Han Chinese patient population. In the first
stage, DNA samples from 68 patients with recurrent HAPE were scanned using
Affymetrix SNP Array 6.0 Chips, and allele frequencies were compared to those of
84 HapMap CHB samples to identify candidate SNPs. In the second stage, the 77
identified candidate SNPs were examined in an independent cohort of samples from
199 HAPE patients and 304 controls. Associations between SNPs and HAPE risk were
tested using various genetic models. Of the 77 original SNPs, 7 were found to be
associated with HAPE susceptibility in the second stage of the study. GO and
pathway enrichment analysis of the 7 SNPs revealed 5 adjacent genes involved in
various processes, including regulation of nucleoside diphosphate metabolism,
thyroid hormone catabolism, and low-density lipoprotein receptor activity. These
results suggest the identified SNPs and genes may contribute to the
physiopathology of HAPE.
PMID- 28415563
TI - GD2 expression in breast cancer.
AB - Breast cancer (BC) is a heterogeneous disease, including different subtypes
having diverse incidence, drug-sensitivity and survival rates. In particular,
claudin-low and basal-like BC have mesenchymal features with a dismal prognosis.
Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a
variety of cancers. Despite its potential relevance in cancer diagnostics and
therapeutics, the presence and role of GD2 require further investigation,
especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC
patients and its correlation with clinical-pathological features.Sixty-three
patients with BC who underwent surgery without prior chemo- and/or radiotherapy
between 2001 and 2014 were considered. Cancer specimens were analyzed by
immunohistochemistry and GD2-staining was expressed according to the percentage
of positive cells and by a semi-quantitative scoring system.Patient
characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor
size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in
59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11
(18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens
stained positive for GD2. The univariate regression logistic analysis revealed a
significant association of GD2 with triple-receptor negative phenotype and older
age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly
prevalent in a cohort of BC patients clustering on very aggressive BC subtypes,
such as triple-negative and metaplastic variants.
PMID- 28415565
TI - Rad52 deficiency decreases development of lung squamous cell carcinomas by
enhancing immuno-surveillance.
AB - RAD52 is involved in homologous recombination and DNA repair. This study focuses
on lung cancer progression and how the DNA repair gene, Rad52, enables tumor
cells to have sufficient genome integrity, i.e., the ability to repair lethal DNA
damage, to avoid cell death. In this report, we analyze the phenotypic
differences between wild type and Rad52-/- in inhibition of tumor phenotypes
including cell growth, viability, cytolysis, and immune profiling. We
demonstrated that loss of Rad52 not only increases the death of cells undergoing
carcinogen-induced transformation in vivo, but that Rad52 loss also augments in
vivo antitumor activity through an enhanced capacity for direct killing of LLC
tumor cells by stimulated Rad52-/- NK and CD8+ T cells. We hypothesize that upon
DNA damage, wild type cells attempt to repair DNA lesions, but those cells that
survive will continue to divide with damage and a high likelihood of progressing
to malignancy. Loss of Rad52, however, appears to increase genomic instability
beyond a manageable threshold, acceding the damaged cells to death before they
are able to become tumor cells. Our results suggest a key role for the complex
interplay between the DNA damage response and host immunity in determining risk
for Squamous Cell Lung Carcinoma.
PMID- 28415566
TI - Co-targeting of DNA, RNA, and protein molecules provides optimal outcomes for
treating osteosarcoma and pulmonary metastasis in spontaneous and experimental
metastasis mouse models.
AB - Metastasis is a major cause of mortality for cancer patients and remains as the
greatest challenge in cancer therapy. Driven by multiple factors, metastasis may
not be controlled by the inhibition of single target. This study was aimed at
assessing the hypothesis that drugs could be rationally combined to co-target
critical DNA, RNA and protein molecules to achieve "saturation attack" against
metastasis. Independent actions of the model drugs DNA-intercalating doxorubicin,
RNA-interfering miR-34a and protein-inhibiting sorafenib on DNA replication, RNA
translation and protein kinase signaling in highly metastatic, human osteosarcoma
143B cells were demonstrated by the increase of gammaH2A.X foci formation,
reduction of c-MET expression and inhibition of Erk1/2 phosphorylation,
respectively, and optimal effects were found for triple-drug combination.
Consequently, triple-drug treatment showed a strong synergism in suppressing 143B
cell proliferation and the greatest effects in reducing cell invasion. Compared
to single- and dual-drug treatment, triple-drug therapy suppressed pulmonary
metastases and orthotopic osteosarcoma progression to significantly greater
degrees in orthotopic osteosarcoma xenograft/spontaneous metastases mouse models,
while none showed significant toxicity. In addition, triple-drug therapy improved
the overall survival to the greatest extent in experimental metastases mouse
models. These findings demonstrate co-targeting of DNA, RNA and protein molecules
as a novel therapeutic strategy for the treatment of metastasis.
PMID- 28415569
TI - Interleukin-2-regulatory T cell axis critically regulates maintenance of
hematopoietic stem cells.
AB - The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice
develop severe anomalies in HSC maintenance leading to defective hematopoiesis.
Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis,
myelopoiesis was enhanced in Il2-/- mice. Investigation of the underlying
mechanisms of dysregulated hematopoiesis in Il2-/- mice shows that the IL-2-Treg
cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of
Treg activity resulted in increased IFN-gamma production by activated T cells and
an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg
population successfully rescued HSC maintenance in Il2-/- mice, preventing IFN
gamma activity could do the same even in the absence of Treg cells. Our study
suggests that equilibrium in IL-2 and IFN-gamma activity is critical for steady
state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN
gamma treatment might help to restore hematopoiesis.
PMID- 28415568
TI - Non-coding RNAs as emerging regulators of epithelial to mesenchymal transition in
non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) remains a major health problem that patients
suffer from around the world. The epithelial to mesenchymal transition (EMT) has
attractive roles in increasing malignant potential and reducing sensitivity to
conventional therapeutics in NSCLC cells. Meanwhile, it is now evident that non
coding RNAs (ncRNAs), primarily microRNAs and long non-coding RNAs contribute to
tumorigenesis partially via regulating EMT. This article briefly summarizes
current researches about EMT-related ncRNAs in NSCLC and discusses their crucial
roles in the complex regulatory network. Also, the authors will show the evidence
that ncRNAs not only contribute to cancer cells migration and invasion, but also
take charge of the resistance of chemotherapy, radiotherapy and EGFR-TIKs. Then,
we will further discuss the potential of inhibition of EMT via manipulating
relevant ncRNAs to change our current treatment of NSCLC patients.
PMID- 28415564
TI - Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges
for SphK as an oncotarget.
AB - The various sphingosine kinase (SphK) isoenzymes (isozymes) and isoforms, key
players in normal cellular physiology, are strongly implicated in cancer and
other diseases. Mutations in SphKs, that may justify abnormal physiological
function, have not been recorded. Nonetheless, there is a large and growing body
of evidence demonstrating the contribution of gain or loss of function and the
imbalance in the SphK/S1P rheostat to a plethora of pathological conditions
including cancer, diabetes and inflammatory diseases. SphK is expressed as two
isozymes SphK1 and SphK2, transcribed from genes located on different chromosomes
and both isozymes catalyze the phosphorylation of sphingosine to S1P. Expression
of each SphK isozyme produces alternately spliced isoforms. In recent years the
importance of the contribution of SpK1 expression to treatment resistance in
cancer has been highlighted and, additionally, differences in treatment outcome
appear to also be dependent upon SphK isoform expression. This review focuses on
an exciting emerging area of research involving SphKs functions, expression and
subcellular localization, highlighting the complexity of targeting SphK in cancer
and also comorbid diseases. This review also covers the SphK isoenzymes and
isoforms from a historical perspective, from their first discovery in murine
species and then in humans, their role(s) in normal cellular function and in
disease processes, to advancement of SphK as an oncotarget.
PMID- 28415570
TI - Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus
erythematosus risk.
AB - The association of polymorphisms in programmed cell death 1 (PDCD1) gene with
systemic lupus erythematosus (SLE) risk is inconsistent across different studies.
This meta-analysis is aimed to provide reliable evidence to the association of
five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE
risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were
included in this meta-analysis. PD1.3 polymorphism was significantly associated
with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA
vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13
1.7). In the stratified analyses based on ethnicity, we found a significant
association in Caucasians and in Mexicans. In the subgroup analyses by gender, a
significant association was found between PD1.3 polymorphism and SLE risk in
males. The results also suggested an association between the PD1.6 polymorphism
and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta
analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE,
particularly in Caucasians, while PD1.6 may be a protective factor to SLE.
PMID- 28415571
TI - Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and
triple-negative essential thrombocythemia.
AB - Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative
neoplasm. We have reported that increased activated B cells can facilitate
platelet production mediated by cytokines regardless JAK2 mutational status in
ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL
unmutated ET and primary myelofibrosis. Here we sought to screen for CALR
mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese
ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell
activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression
and intracellular levels of interleukin (IL)-1beta/IL-6 and the expression of
CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration
was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of
54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%)
patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation,
CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet
count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count
(p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and
hematological parameters confirmed that increased activated B cells were
universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients
when compared to healthy adults. JAK2- and CALR-mutated ET have significantly
higher fraction of B cells with TLR4 expression when compared to triple-negative
ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher
number of CD69-positive activated B cells when compared to triple-negative ET
(p=0.035). In conclusion, increased B cell activation is present in ET patients
across different mutational subgroups.
PMID- 28415572
TI - Inhibition of iron overload-induced apoptosis and necrosis of bone marrow
mesenchymal stem cells by melatonin.
AB - Iron overload induces severe damage to several vital organs such as the liver,
heart and bone, and thus contributes to the dysfunction of these organs. The aim
of this study is to investigate whether iron overload causes the apoptosis and
necrosis of bone marrow mesenchymal stem cells (BMSCs) and melatonin may prevent
its toxicity. Perls' Prussion blue staining showed that exposure to increased
concentrations of ferric ammonium citrate (FAC) induced a gradual increase of
intracellular iron level in BMSCs. Trypan blue staining demonstrated that FAC
decreased the viability of BMSCs in a concentration-dependent manner. Notably,
melatonin protected BMSCs against apoptosis and necrosis induced by FAC and it
was vertified by Live/Dead, TUNEL and PI/Hoechst stainings. Furthermore,
melatonin pretreatment suppressed FAC-induced reactive oxygen species
accumulation. Western blot showed that exposure to FAC resulted in the decrease
of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bax and
Cleaved Caspase-3, and necrosis-related proteins RIP1 and RIP3, which were
significantly inhibited by melatonin treatment. At last, melatonin receptor
blocker luzindole failed to block the protection of BMSCs apoptosis and necrosis
by melatonin. Taken together, melatonin protected BMSCs from iron overload
induced apoptosis and necrosis by regulating Bcl-2, Bax, Cleaved Caspase-3, RIP1
and RIP3 pathways.
PMID- 28415573
TI - Elevated TATA-binding protein expression drives vascular endothelial growth
factor expression in colon cancer.
AB - The TATA-binding protein (TBP) plays a central role in eukaryotic gene
transcription. Given its key function in transcription initiation, TBP was
initially thought to be an invariant protein. However, studies showed that TBP
expression is upregulated by oncogenic signaling pathways. Furthermore, depending
on the cell type, small increases in cellular TBP amounts can induce changes in
cellular growth properties towards a transformed phenotype. Here we sought to
identify the specific TBP-regulated gene targets that drive its ability to induce
tumorigenesis. Using microarray analysis, our results reveal that increases in
cellular TBP concentrations produce selective alterations in gene expression that
include an enrichment for genes involved in angiogenesis. Accordingly, we find
that TBP levels modulate VEGFA expression, the master regulator of angiogenesis.
Increases in cellular TBP amounts induce VEGFA expression and secretion to
enhance cell migration and tumor vascularization. TBP mediates changes in VEGFA
transcription requiring its recruitment at a hypoxia-insensitive proximal TSS,
revealing a mechanism for VEGF regulation under non-stress conditions. The
results are clinically relevant as TBP expression is significantly increased in
both colon adenocarcinomas as well as adenomas relative to normal tissue.
Furthermore, TBP expression is positively correlated with VEGFA expression.
Collectively, these studies support the idea that increases in TBP expression
contribute to enhanced VEGFA transcription early in colorectal cancer development
to drive tumorigenesis.
PMID- 28415574
TI - Prognostic roles of Notch receptor mRNA expression in human ovarian cancer.
AB - Aberrant activation of Notch signaling pathway has been correlated with high
grade ovarian carcinoma and carcinogenesis. However, the predictive and
prognostic values of Notch signaling pathway in ovarian cancer patients remains
unclear. We utilize "The Kaplan-Meier plotter" (KM plotter) background database
to access the prognostic values including overall survival (OS), progression-free
survival (PFS), as well as post-progression survival (PPS) of four Notch receptor
mRNA expression in ovarian cancer patients. Notch1 mRNA high expression was not
correlated with OS, PFS and PPS for all ovarian cancer patients, but
significantly correlated with poor PFS in TP53 wild type and favorite PFS in TP53
mutation type ovarian cancer patients. Notch2 mRNA high expression was
significantly correlated with poor PFS for all ovarian cancer patients,
especially in grade II patients. Notch3 mRNA high expression was significantly
correlated with favorite PFS for all ovarian cancer patients. Notch4 mRNA high
expression was significantly correlated with favorite OS, but not PFS and PPS for
all ovarian cancer patients. The results strongly support that there are distinct
prognostic values of four Notch receptor mRNA expression in ovarian cancer
patients.
PMID- 28415575
TI - IK channel activation increases tumor growth and induces differential behavioral
responses in two breast epithelial cell lines.
AB - Many potassium channel families are over-expressed in cancer, but their
mechanistic role in disease progression is poorly understood. Potassium channels
modulate membrane potential (Vmem) and thereby influence calcium ion dynamics and
other voltage-sensitive signaling mechanisms, potentially acting as
transcriptional regulators. This study investigated the differential response to
over-expression and activation of a cancer-associated potassium channel, the
intermediate conductance calcium-activated potassium channel (IK), on aggressive
behaviors in mammary epithelial and breast cancer cell lines. IK was over
expressed in the highly metastatic breast cancer cell line MDA-MB-231 and the
spontaneously immortalized breast epithelial cell line MCF-10A, and the effect on
cancer-associated behaviors was assessed. IK over-expression increased primary
tumor growth and metastasis of MDA-MB-231 in orthotopic xenografts, demonstrating
for the first time in any cancer type that increased IK is sufficient to promote
cancer aggression. The primary tumors had similar vascularization as determined
by CD31 staining and similar histological characteristics. Interestingly, despite
the increased in vivo growth and metastasis, neither IK over-expression nor
activation with agonist had a significant effect on MDA-MB-231 proliferation,
invasion, or migration in vitro. In contrast, IK decreased MCF-10A proliferation
and invasion through Matrigel but had no effect on migration in a scratch-wound
assay. We conclude that IK activity is sufficient to promote cell aggression in
vivo. Our data provide novel evidence supporting IK and downstream signaling
networks as potential targets for cancer therapies.
PMID- 28415576
TI - Clinicopathological features of small cell carcinoma of the uterine cervix in the
surveillance, epidemiology, and end results database.
AB - To investigate the clinicopathological characteristics and survival of small cell
carcinoma of the cervix using Surveillance, Epidemiology, and End Results
database. Patients with a diagnosis of small cell carcinoma of the cervix were
included between 1988 and 2012. Kaplan-Meier method and Cox regression models
were used. A total of 487 patients were included. Of the patients with known
International Federation of Gynecology and Obstetrics stage and tumor grade, the
stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly
or undifferentiated histology. The 5-year cause specific survival and overall
survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing
age, advanced stage, and treatment by primary radiotherapy were associated with
worse survival outcomes. Small cell carcinoma of the cervix is a rare disease
with aggressive characteristics and prone to metastasize and is dismal in
prognosis. Reduced survival was associated with increasing age, advanced stage,
and treatment by primary radiotherapy.
PMID- 28415577
TI - High expression of B7-H6 in human glioma tissues promotes tumor progression.
AB - B7-H6, a new member of B7-family ligand, also known as NCR3LG1, plays an
important role in NK cells mediated immune responses. Many studies have shown
that it is highly expressed in various human cancers, and its expression levels
are significantly associated with cancer patients' clinicopathological parameters
and postoperative prognoses. But, still the exact role of B7-H6 expression in
human glioma remains elusive. In the present study, we have characterized the B7
H6 expression in the human glioma tissues as well as glioma cell lines, U87 and
U251. We observed that B7-H6 was highly expressed in the human glioma tissues,
and its expression was significantly associated with cancer progression. By using
the RNA interference technology, we successfully ablated B7-H6 expression in
human glioma cell lines to further study its contribution towards various
biological features of this malignancy. Our study identified that the B7-H6
knockdown in U87 and U251 glioma cells significantly suppressed cell
proliferation, migration, invasion, and enhanced apoptosis along with induction
of cell cycle arrest. It thus suggested that B7-H6 play an important role in the
regulation of the biological behavior of these glioma cells. However, the
detailed mechanism of B7-H6 mediated regulation of glioma cancer cell
transformation and its prognostic value merits further investigation.
PMID- 28415578
TI - High expression of miR-125b-2 and SNORD116 noncoding RNA clusters characterize
ERG-related B cell precursor acute lymphoblastic leukemia.
AB - ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL)
subtype characterized by aberrant expression of DUX4 and ERG transcription
factors, and highly recurrent ERG intragenic deletions. ERG-related patients have
remarkably favorable outcome despite a high incidence of inauspicious IKZF1
aberrations.We describe clinical and genomic features of the ERG-related cases in
an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP
ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific
of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21
and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan
SNORD116 cluster.
PMID- 28415579
TI - Metabolite marker discovery for the detection of bladder cancer by comparative
metabolomics.
AB - Bladder cancer is one of the most common urinary tract carcinomas in the world.
Urine metabolomics is a promising approach for bladder cancer detection and
marker discovery since urine is in direct contact with bladder epithelia cells;
metabolites released from bladder cancer cells may be enriched in urine samples.
In this study, we applied ultra-performance liquid chromatography time-of-flight
mass spectrometry to profile metabolite profiles of 87 samples from bladder
cancer patients and 65 samples from hernia patients. An OPLS-DA classification
revealed that bladder cancer samples can be discriminated from hernia samples
based on the profiles. A marker discovery pipeline selected six putative markers
from the metabolomic profiles. An LLE clustering demonstrated the discriminative
power of the chosen marker candidates. Two of the six markers were identified as
imidazoleacetic acid whose relation to bladder cancer has certain degree of
supporting evidence. A machine learning model, decision trees, was built based on
the metabolomic profiles and the six marker candidates. The decision tree
obtained an accuracy of 76.60%, a sensitivity of 71.88%, and a specificity of
86.67% from an independent test.
PMID- 28415580
TI - The N-terminal polypeptide derived from viral macrophage inflammatory protein II
reverses breast cancer epithelial-to-mesenchymal transition via a PDGFRalpha
dependent mechanism.
AB - NT21MP, a 21-residue peptide derived from the viral macrophage inflammatory
protein II, competed effectively with the natural ligand of CXC chemokine
receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and
inhibit growth in breast cancer. Its role in tumor epithelial-to-mesenchymal
transition (EMT) regulation remains unknown. In this study, we evaluated the
reversal of EMT upon NT21MP treatment and examined its role in the inhibition of
EMT in breast cancer. The parental cells of breast cancer (SKBR-3 and MCF-7) and
paclitaxel-resistant (SKBR-3 PR and MCF-7 PR) cells were studied in vitro and in
combined immunodeficient mice. The mice injected with SKBR-3 PR cells were
treated with NT21MP through the tail vein or intraperitoneally with paclitaxel or
saline. Sections from tumors were evaluated for tumor weight and EMT markers
based on Western blot. In vitro, the effects of NT21MP, CXCR4 and PDGFRalpha on
tumor EMT were assessed by relative quantitative real-time reverse transcription
polymerase chain reaction, western blot and biological activity in breast cancer
cell lines expressing high or low levels of CXCR4. Our results illustrated that
NT21MP could reverse the phenotype of EMT in paclitaxel-resistant cells.
Furthermore, we found that NT21MP governed PR-mediated EMT partly due to
controlling platelet-derived growth factors A and B (PDGFA and PDGFB) and their
receptor (PDGFRalpha). More importantly, NT21MP down-regulated AKT and ERK1/2
activity, which were activated by PDGFRalpha, and eventually reversed the EMT.
Together, these results indicated that CXCR4 overexpression drives acquired
paclitaxel resistance, partly by activating the PDGFA and PDGFB/PDGFRalpha
autocrine signaling loops that activate AKT and ERK1/2. Inhibition of the
oncogenic EMT process by targeting CXCR4/PDGFRalpha-mediated pathways using
NT21MP may provide a novel therapeutic approach towards breast cancer.
PMID- 28415581
TI - Tumor physiological changes during hypofractionated stereotactic body radiation
therapy assessed using multi-parametric magnetic resonance imaging.
AB - Radiation therapy is a primary treatment for non-resectable lung cancer and
hypoxia is thought to influence tumor response. Hypoxia is expected to be
particularly relevant to the evolving new radiation treatment scheme of
hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought
to develop non-invasive tools to assess tumor pathophysiology and response to
irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen
level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to
explore the longitudinal effects of SBRT on tumor oxygenation and vascular
perfusion using A549 human lung cancer xenografts in a subcutaneous rat model.
Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD,
T2* and DCE. At baseline, most tumors showed a positive BOLD signal response
(%DeltaSI) and increased T2* in response to oxygen breathing challenge,
indicating increased vascular oxygenation. Control tumors showed similar response
24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the
irradiated tumors showed a significantly decreased T2* (-2.9+/-4.2 ms) and
further decrease was observed (-4.0+/-6.0 ms) after 1 week, suggesting impaired
vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal
changes following irradiation. Rats were cured of the primary tumors by 3x12 Gy,
providing long term survival, though with ultimate metastatic recurrence.
PMID- 28415582
TI - Respiratory status determines the effect of emodin on cell viability.
AB - The anthraquinone emodin has been shown to have antineoplastic properties and a
wealth of unconnected effects have been linked to its use, most of which are
likely secondary outcomes of the drug treatment. The primary activity of emodin
on cells has remained unknown. In the present study we demonstrate dramatic and
extensive effects of emodin on the redox state of cells and on mitochondrial
homeostasis, irrespectively of the cell type and organism, ranging from the yeast
Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to
redox-active enzymes and its effectiveness depends on the oxidative and
respiratory status of cells. We show that cells with efficient respiratory
metabolism are less susceptible to emodin, whereas cells under glycolytic
metabolism are more vulnerable to the compound. Our findings indicate that emodin
acts in a similar way as known uncouplers of the mitochondrial electron transport
chain and causes oxidative stress that particularly disturbs cancer cells.
PMID- 28415583
TI - Prognostic value of circulating endothelial cells in metastatic colorectal
cancer.
AB - BACKGROUND: There is urgent need for improved staging in patients with metastatic
colorectal cancer (mCRC). In this study, we evaluated the prognostic value of
circulating endothelial cells (CEC) in comparison with circulating tumor cells
(CTC) in patients with mCRC amenable for potentially curative surgery. METHODS: A
total of 140 patients were enrolled prospectively. CTC and CEC were measured with
the CellSearch System (Veridex, NJ, USA). Cut-off values were determined using
ROC analyses. Prognostic factors were identified by Cox proportional hazards
models. RESULTS: ROC analyses revealed >= 21 CEC as cut-off levels for detection,
which was present in 68 (49%). CEC detection was associated with female gender (p
= 0.03) only, whereas CTC detection was associated with presence of the primary
tumor (p = 0.007), metastasis size (p < 0.001), bilobar liver metastases (p =
0.02), CEA (p < 0.001) and CA 19-9 levels (p < 0.001). On multivariate analysis
only CEC detection (HR 1.81; p = 0.03) and preoperative CA19-9 levels (HR 2.28, p
= 0.005) were revealed as independent predictors of poor survival. CONCLUSIONS:
CEC are of stronger prognostic value than CTC. Further studies are required to
validate these results and to evaluate CEC as predictive biomarker for systemic
therapy alone as well as in combination with other markers such as CA19-9.
PMID- 28415584
TI - Folic acid phenotype (FAP) is a superior biomarker predicting response to
pemetrexed-based chemotherapy in malignant pleural mesothelioma.
AB - BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare tumor linked to a
dismal prognosis. Even the most effective chemotherapeutical regime of pemetrexed
combined with cisplatin leads to a remission-rate of only about 40%. The reasons
for the rather poor efficacy remain largely unknown. RESULTS: Phenotypes were
significantly associated with progression (p=0.0279) and remission (p=0.0262).
Cox-regression revealed significant associations between SLC19A1/TYMS-ratio
(p=0.0076) as well as FPGS/TYMS-ratio (p=0.0026) and OS. For differentiation by
risk-groups, COXPH identified a strong correlation (p=0.0008). METHODS: 56 MPM
specimens from patients treated with pemetrexed were used for qPCR analysis.
Phenotypes and risk groups were defined by their expression levels of members of
the folic acid metabolism and correlated to survival and objective response.
CONCLUSION: Our results indicate that the balance between folic acid uptake,
activation and metabolism plays a crucial role in response to pemetrexed-based
chemotherapy and the prognosis of MPM patients. Implementing this marker profile
in MPM stratification may help to individualize MPM-therapy more efficiently.
PMID- 28415586
TI - Promoting oligodendroglial-oriented differentiation of glioma stem cell: a
repurposing of quetiapine for the treatment of malignant glioma.
AB - As a major contributor of chemotherapy resistance and malignant recurrence,
glioma stem cells (GSCs) have been proposed as a target for the treatment of
gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical
antipsychotic, for the treatment of malignant glioma, we established mouse models
with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft
tumors, using GSCs purified from glioblastoma cell line GL261. We investigated
antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on
GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress
GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide
(TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ
resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the
anti-glioma effect of QUE was due to its actions of promoting the differentiation
of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the
Wnt/beta-catenin signaling pathway. Together, our findings suggest an effective
approach for anti-gliomagenic treatment via targeting OL-oriented differentiation
of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for
the treatment of malignant glioma.
PMID- 28415587
TI - Detection of a combination of serum IgG and IgA antibodies against selected
mycobacterial targets provides promising diagnostic signatures for active TB.
AB - Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB)
disease often show a lack of specificity in TB endemic regions, which is mainly
due to a high background prevalence of LTBI. Here, we investigated the combined
performance of the responses of different Ig classes to selected mycobacterial
antigens in primary healthcare clinic attendees with signs and symptoms
suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM
and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and
19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals
who underwent diagnostic work-up for TB after presenting with symptoms and signs
compatible with possible active TB were evaluated. Active TB was excluded in 42
individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of
whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The
leading single serodiagnostic markers to differentiate between the presence or
absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and
specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4
antibodies further improved this performance to accuracies above 95%. After
successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA
and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased.
These results show the potential of extending investigation of anti-tuberculous
IgG responses to include IgM and IgA responses against selected protein and non
protein antigens in differentiating active TB from other respiratory diseases in
TB endemic settings.
PMID- 28415588
TI - Smad inhibitor induces CSC differentiation for effective chemosensitization in
cyclin D1- and TGF-beta/Smad-regulated liver cancer stem cell-like cells.
AB - Understanding cancer stem cell (CSC) maintenance pathways is critical for the
development of CSC-targeting therapy. Here, we investigated the functional role
of the cyclin D1-dependent activation of Smad2/3 and Smad4 in hepatocellular
carcinoma (HCC) CSCs and in HCC primary tumors. Cyclin D1 sphere-derived
xenograft tumor models were employed to evaluate the therapeutic effects of a
Smad inhibitor in combination with chemotherapy. Cyclin D1 overexpression confers
stemness properties by enhancing single sphere formation, enhancing the CD90+ and
EpCAM+ population, increasing stemness gene expression, and increasing
chemoresistance. Cyclin D1 interacts with and activates Smad2/3 and Smad4 to
result in cyclin D1-Smad2/3-Smad4 signaling-regulated liver CSC self-renewal. The
cyclin D1-dependent activation of Smad2/3 and Smad4 is also found in HCC patients
and predicts disease progression. A Smad inhibitor impaired cyclin D1-Smad
mediated self-renewal, resulting in the chemosensitization. Thus, pretreatment
with a Smad inhibitor followed by chemotherapy not only successfully suppressed
tumor growth but also eliminated 57% of the tumors in a cyclin D1 sphere-derived
xenograft model. Together, The cyclin D1-mediated activation of Smad2/3 and Smad4
is an important regulatory mechanism in liver CSC self-renewal and stemness.
Accordingly, a Smad inhibitor induced CSC differentiation and consequently
significant chemosensitization, which could be an effective strategy to target
CSCs.
PMID- 28415589
TI - GABAergic neurons in nucleus accumbens are correlated to resilience and
vulnerability to chronic stress for major depression.
AB - BACKGROUND: Major depression, persistent low mood, is one of common psychiatric
diseases. Chronic stressful life is believed to be a major risk factor that leads
to dysfunctions of the limbic system. However, a large number of the individuals
with experiencing chronic stress do not suffer from major depression, called as
resilience. Endogenous mechanisms underlying neuronal invulnerability to chronic
stress versus major depression are largely unknown. As GABAergic neurons are
vulnerable to chronic stress and their impairments is associated with major
depression, we have examined whether the invulnerability of GABAergic neurons in
the limbic system is involved in resilience. RESULTS: GABAergic neurons in the
nucleus accumbens from depression-like mice induced by chronic unpredictable mild
stress appear the decreases in their GABA release, spiking capability and
excitatory input reception, compared with those in resilience mice. The levels of
decarboxylase and vesicular GABA transporters decrease in depression-like mice,
but not resilience. MATERIALS AND METHODS: Mice were treated by chronic
unpredictable mild stress for three weeks. Depression-like behaviors or
resilience was confirmed by seeing whether their behaviors change significantly
in sucrose preference, Y-maze and forced swimming tests. Mice from controls as
well as depression and resilience in response to chronic unpredictable mild
stress were studied in terms of GABAergic neuron activity in the nucleus
accumbens by cell electrophysiology and protein chemistry. CONCLUSIONS: The
impairment of GABAergic neurons in the nucleus accumbens is associated with major
depression. The invulnerability of GABAergic neurons to chronic stress may be one
of cellular mechanisms for the resilience to chronic stress.
PMID- 28415590
TI - Multiple anti-tumor effects of Reparixin on thyroid cancer.
AB - BACKGROUND: Expression of IL-8 and its receptors CXCR1 and CXCR2 is a common
occurrence in human epithelial thyroid cancer (TC). In human TC samples, IL-8
expression is associated with tumor progression. IL-8 enhances proliferation,
survival, motility, and leads to the maintenance of stemness features and tumor
initiating ability of TC cells. Here, we studied the effects of Reparixin
(formerly Repertaxin), a small molecular weight CXCR1 and CXCR2 inhibitor, on the
malignant phenotype of various TC cell lines. RESULTS: Reparixin impaired the
viability of epithelial thyroid cancerous cells, but not that of the non
malignant counterpart. Reparixin treatment significantly decreased TC cell
survival, proliferation, Epithelial-to-Mesenchymal Transition (EMT) and stemness.
CXCR1 and CXCR2 silencing abolished these effects. Reparixin sensitized TC cells
to Docetaxel and Doxorubicin in culture. Used as single agent, Reparixin
significantly inhibited TC cell tumorigenicity in immunodeficient mice. Finally,
Reparixin potentiated the effects of Docetaxel on TC cell xenotransplants in
mice. MATERIALS AND METHODS: We assessed the effects of Reparixin on TC cell
viability (by growth curves, BrdU incorporation, TUNEL assay), EMT (by RT-PCR,
Flow Cytometry, Migration assays), stemness (by RT-PCR, Flow Cytometry, sphere
formation and self-renewal), and tumorigenicity (by xenotransplantation in nude
mice). CONCLUSIONS: The present study suggests that Reparixin, both alone and in
combination with classic chemotherapics, represents a novel potential therapeutic
strategy for aggressive forms of TC.
PMID- 28415591
TI - The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and
fibroblasts in fibrotic lung disease.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating disease with few available
treatment options. Recently, the involvement of purinergic receptor subtypes in
the pathogenesis of different lung diseases has been demonstrated. Here we
investigated the role of the purinergic receptor subtype P2Y2 in the context of
fibrotic lung diseases.The concentration of different nucleotides was measured in
the broncho-alveolar lavage (BAL) fluid derived from IPF patients and animals
with bleomycin-induced pulmonary fibrosis. In addition expression of P2Y2
receptors by different cell types was determined. To investigate the functional
relevance of P2Y2 receptors for the pathogenesis of the disease the bleomycin
model of pulmonary fibrosis was used. Finally, experiments were performed in
pursuit of the involved mechanisms.Compared to healthy individuals or vehicle
treated animals, extracellular nucleotide levels in the BAL fluid were increased
in patients with IPF and in mice after bleomycin administration, paralleled by a
functional up-regulation of P2Y2R expression. Both bleomycin-induced inflammation
and fibrosis were reduced in P2Y2R-deficient compared to wild type animals.
Mechanistic studies demonstrated that recruitment of neutrophils into the lungs,
proliferation and migration of lung fibroblasts as well as IL6 production are key
P2Y2R mediated processes.Our results clearly demonstrate the involvement of P2Y2R
subtypes in the pathogenesis of fibrotic lung diseases in humans and mice and
hence support the development of selective P2Y2R antagonists for the treatment of
IPF.
PMID- 28415592
TI - Identification and functional analysis of differentially expressed genes in
poorly differentiated hepatocellular carcinoma using RNA-seq.
AB - Poorly differentiated (PD) hepatocellular carcinoma (HCC) has a worse prognosis
compared to moderately differentiated (MD) and well differentiated (WD) HCC. We
aimed to identify differentially expressed genes (DEGs) to explore the mechanism
of PD HCC. Transcriptome sequencing was performed on tumor and adjacent non
tumorous tissues of PD, MD and WD HCC patients (3 for each group). DEGs were thus
identified and functionally analyzed. Further RT-PCR was performed to validate
DEGs specific for PD HCC in 47 pairs of samples (15 for PD, 18 for MD, 14 for
WD). A total of 681 PD DEGs were detected, including 368 up-regulated and 313
down-regulated genes. Less DEGs were found for MD and especially for WD HCC.
Through bioinformatics analysis, PD HCC DEGs were enriched in liver tissue and
liver cancer cells, and in biological process and pathway including metabolism,
cell cycle, translation and blood coagulation. Potential drugs and genetic
perturbations were found to reverse the cancer condition. The RT-PCR results
showed consistency with RNA-seq in the validation of 4 DEGs specific for PD HCC.
This study detected and validated DEGs of PD HCC, which provides useful
information on molecular mechanism of PD HCC for development of new biomarkers,
therapeutic targets and drugs.
PMID- 28415594
TI - Interaction of Epstein-Barr virus genes with human gastric carcinoma
transcriptome.
AB - Gastric carcinoma (GC) is a leading cause of mortality. 10% of GC cases are
related with EBV (Epstein-Barr virus) infection. The detailed mechanistic roles
EBV genes play and especially the interaction between the viral genes and human
genes in GC remain unclear. In this study, raw fastq data from 285 GC samples
were downloaded from TCGA (The Cancer Genome Atlas), including 25 EBV positive
(EBV+) GC samples and 260 EBV negative (EBV-) GC samples. RNA-seq based
expression data were generated for both human genes (among all the samples) and
for the EBV genes (among the 25 EBV+ samples). Bioinformatics analyses were
performed to identify differentially expressed (DEx) human genes and DEx KEGG
pathways in EBV+ vs. EBV- samples and co-expressed human gene modules and hub
genes among the DEx genes. Within the EBV+ samples, analyses were conducted to
find correlation between EBV gene expression and the human gene expression
modules, between EBV gene expression and the human hub genes, and between EBV
gene expression and the DEx human pathways. EBV genes LMP-1, BALF1 and BALF2 were
found to have significant correlation with human hub genes, CNTD2 and VANGL2. EBV
genes BALF4 and BALF5 were found to correlate with human pathways, including Jak
STAT signaling and Phosphatidylinositol Signaling System. Our study has revealed
the coordinated expression patterns between EBV and human GC transcriptome and
identified several key EBV genes that may play an important role in EBV+ GC
pathogenesis through their interactions with human genes and pathways.
PMID- 28415593
TI - Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with
leukemia relapse and leukemia-free survival in adults with B-cell acute
lymphoblastic leukemia and normal cytogenetics.
AB - Relapse is the major cause of treatment-failure in adults with B-cell acute
lymphoblastic leukemia (ALL) achieving complete remission after induction
chemotherapy. Greater precision identifying persons likely to relapse is
important. We did bio-informatics analyses of transcriptomic data to identify
mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate
genes for validation 7 of which proved significantly-associated with B-cell ALL.
We next focused on function and clinical correlations of the cysteine and glycine
rich protein 2 (CSRP2). Quantitative real-time polymerase chain reaction (RT
qPCR) was used to examine gene transcript levels in bone marrow samples from 236
adults with B-cell ALL compared with samples from normals. CSRP2 was over
expressed in 228 out of 236 adults (97%) with newly-diagnosed B-cell ALL. A
prognostic value was assessed in 168 subjects. In subjects with normal
cytogenetics those with high CSRP2 transcript levels had a higher 5-year
cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS)
compared with subjects with low transcript levels (56% [95% confidence interval,
53, 59%] vs. 19% [18, 20%]; P = 0.011 and 41% [17, 65%] vs. 80% [66-95%]; P =
0.007). In multivariate analyses a high CSRP2 transcript level was independently
associated with CIR (HR = 5.32 [1.64-17.28]; P = 0.005) and RFS (HR = 5.56 [1.87,
16.53]; P = 0.002). Functional analyses indicated CSRP2 promoted cell
proliferation, cell-cycle progression, in vitro colony formation and cell
migration ability. Abnormal CSRP2 expression was associated with resistance to
chemotherapy; sensitivity was restored by down-regulating CSRP2 expression.
PMID- 28415595
TI - 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast
cancer.
AB - PURPOSE: In bone-metastatic breast cancer patients, there are no current imaging
biomarkers to identify which patients have worst prognosis. The purpose of our
study was to investigate if skeletal tumor burden determined by 18F-Fluoride
PET/CT correlates with clinical outcomes and may help define prognosis throughout
the course of the disease. RESULTS: Bone metastases were present in 49 patients.
On multivariable analysis, skeletal tumor burden was significantly and
independently associated with overall survival (p < 0.0001) and progression free
survival (p < 0.0001). The simple presence of bone metastases was associated with
time to bone event (p = 0.0448). MATERIALS AND METHODS: We quantified the
skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer
patients (40 for primary staging and the remainder for restaging after therapy).
Clinical parameters, primary tumor characteristics and skeletal tumor burden were
correlated to overall survival, progression free-survival and time to bone event.
The median follow-up time was 19.5 months. CONCLUSIONS: 18F-Fluoride PET/CT
skeletal tumor burden is a strong independent prognostic imaging biomarker in
breast cancer patients.
PMID- 28415596
TI - Renal mass biopsy using Raman spectroscopy identifies malignant and benign renal
tumors: potential for pre-operative diagnosis.
AB - The accuracy of renal mass biopsy to diagnose malignancy can be affected by
multiple factors. Here, we investigated the feasibility of Raman spectroscopy to
distinguish malignant and benign renal tumors using biopsy specimens. Samples
were collected from 63 patients who received radical or partial nephrectomy, mass
suspicious of cancer and distal parenchyma were obtained from resected kidney
using an 18-gauge biopsy needle. Four Raman spectra were obtained for each
sample, and Discriminant Analysis was applied for data analysis. A total of 383
Raman spectra were eventually gathered and each type of tumor had its
characteristic spectrum. Raman could separate tumoral and normal tissues with an
accuracy of 82.53%, and distinguish malignant and benign tumors with a
sensitivity of 91.79% and specificity of 71.15%. It could classify low-grade and
high-grade tumors with an accuracy of 86.98%. Besides, clear cell renal carcinoma
was differentiated with oncocytoma and angiomyolipoma with accuracy of 100% and
89.25%, respectively. And histological subtypes of cell carcinoma were
distinguished with an accuracy of 93.48%. When compared with final pathology and
biopsy, Raman spectroscopy was able to correctly identify 7 of 11 "missed" biopsy
diagnoses. These results suggested that Raman may serve as a promising non
invasive approach in the future for pre-operative diagnosis.
PMID- 28415597
TI - Phosphorylation of androgen receptors at serine 515 is a potential prognostic
marker for triple negative breast cancer.
AB - 1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths.
Molecular classifications of breast cancer have resulted in improved treatments.
However, treatments for triple negative breast cancer (TNBC) are lacking.
Analysis of molecular targets for TNBC is a priority. One potential candidate is
androgen receptor (AR) phosphorylation. This study assessed the role of AR
phosphorylation at ser81/ser515 and their two upstream effectors, cyclin
dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in
332 ductal breast cancer patients by immunohistochemistry.pERK1/2 combined with
AR-515 associated with improved cancer-specific survival (CSS, p = 0.038),
decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b
lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor
(ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore
stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with
AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004),
invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased
plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR
515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515
associated with decreased inflammation (p = 0.003), increased tumour stroma (p =
0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p =
0.065) and macrophage levels (p = 0.093).In Conclusions, AR-515 may be an
important regulator of inflammation in breast cancer potential via ERK1/2
phosphorylation. AR-515 is a potential prognostic marker and therapeutic target
for TNBC.
PMID- 28415598
TI - Caloric restriction delays early phases of carcinogenesis via effects on the
tissue microenvironment.
AB - Caloric restriction (CR) is an effective and consistent means to delay aging and
the incidence of chronic diseases related to old age, including cancer. However,
the precise mechanisms responsible for the beneficial effect of CR on
carcinogenic process are yet to be identified.In the present studies the
hypothesis was tested that the CR might delay carcinogenesis via modulatory
effects exerted on the age-associated, neoplastic-prone tissue microenvironment.
Using a well characterized, orthotopic cell transplantation (Tx) system in the
rat, preneoplastic hepatocytes isolated from liver nodules were injected into
either old syngeneic rats fed ad libitum (AL) or animals of the same age given a
CR diet (70% of AL feeding). Analysis of donor-derived cell clusters performed at
10 weeks post-Tx revealed a significant shift towards smaller class sizes in the
group receiving CR diet. Clusters comprising more than 50 cells, including large
hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of
spontaneous endogenous nodules was also decreased by CR. Markers of cell
senescence were equally expressed in the liver of AL and CR groups. However,
higher levels of SIRT1 and FOXO1 proteins were detected in CR-exposed livers,
while expression of HDAC1 and C/EBPbeta were decreased. These results are
interpreted to indicate that CR delays the emergence of age-associated neoplastic
disease through effects exerted, at least in part, on the tissue
microenvironment. Nutrient-sensing pathways might mediate such modulatory effect.
PMID- 28415599
TI - BRCA1 missense polymorphisms are associated with poor prognosis of pancreatic
cancer patients in a Chinese population.
AB - Pancreatic cancer is a highly lethal disease with limited prognostic marker.
BRAC1 and BRCA2 are two classic tumor suppressor genes which play an important
role in DNA repair. Somatic mutations and germline genetic variants on BRCA1/2
have been found associated with the tumorigenesis of pancreatic cancer. However,
the correlations between BRCA1/2 polymorphism and pancreatic cancer prognosis
remained unknown. In this study, we genotyped three tag missense variants on
BRCA1/2 in 603 sporadic pancreatic cancer patients in a Chinese population. We
found rs1799966 on BRCA1 was associated with poor prognosis of pancreatic cancer
patients with hazard ratio being 1.23 (95% CI: 1.09-1.40, P = 0.0010). Further
stratification analyses showed that significant correlation was particularly in
locally advanced stage patients with hazard ratio being 1.36 (95% CI: 1.13-1.64,
P = 0.0014), but not in patients in local stage (P = 0.1139) or metastatic stage
(P = 0.5185). Two missense variants (rs766173 and rs144848) on BRAC2 showed no
significant correlation with pancreatic cancer patients' overall survival. In
conclusion, we identified a germline missense variant on BRAC1 significantly
associated with poor prognosis of pancreatic cancer patients with locally
advanced stage. These results may contribute to the precision medicine of this
disease.
PMID- 28415600
TI - The value of MRI in evaluating the efficacy and complications with the treatment
of intra-arterial chemotherapy for retinoblastoma.
AB - Retinoblastoma is the most common intraocular malignant tumor of childhood. Intra
arterial chemotherapy (IAC) is a recently popularized technique used for the
treatment of retinoblastoma, to decrease mortality, increase preservation of the
eye, and prevent blindness. Along with the extensive use of IAC, it is important
to apply noninvasive examination methods to assess the activity of the tumor and
the risk factors for disease dissemination without histopathological
confirmation. There are few studies that have assessed the value of magnetic
resonance imaging (MRI) in evaluating the efficacy and complications of IAC for
retinoblastoma. We retrospectively analyzed the MRI features of 60 patients with
unilateral retinoblastoma given the primary treatment of IAC from January 2014 to
February 2016 in our hospital. Our study showed that MRI could well assess the
decreased activity of the tumor after IAC, presenting with diminished tumor size,
increased apparent diffusion coefficient (ADC) values (from 0.94 +/- 0.24 * 10-3
mm2/s to 2.24 +/- 0.40 * 10-3 mm2/s), and a reduced degree of enhancement of the
tumor. Our study also showed that MRI can monitor the risk factors of abnormal
enhancement of the postlaminar optic nerve, to avoid unnecessary enucleation.
Meanwhile, the results showed that the main late complications after IAC included
affected eyeball volume reduction, subretinal hemorrhage, vitreous hemorrhage,
vitreous opacity, cataractous len, and choroidal vascular ischemia.
PMID- 28415601
TI - Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia.
AB - GATA3 polymorphisms were reported to be significantly associated with
susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by
impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism
located around in the tissue-specific enhancer, and significantly associated with
GATA3 expression. Although the regulatory network of GATA3 has been well reported
in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus
conducted genome-wide gene expression association analyses to reveal expression
associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL
patients, 173 candidates were identified to be significantly associated with
GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and
well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit
tissue-specific and subtype-specific association with GATA3. Through
overexpression and down-regulation of GATA3 in leukemia cell lines, several
reported and novel GATA3 regulated genes were validated. Moreover, association of
GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which
locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may
be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL
to impact leukemogenesis through epigenetic regulation.
PMID- 28415603
TI - Synthesis and evaluation of anthranilamide-based derivatives as FXa inhibitors.
AB - Factor Xa (FXa) plays a significant role in the blood coagulation cascade and is
a promising target for anticoagulation drugs. Three oral FXa inhibitors have been
approved by FDA for treating thrombotic diseases. In this study, 43 novel
compounds were synthesized anthranilamide-based FXa inhibitors aiming to
ameliorate the toxicity of traditional FXa inhibitors in clinic. The data
indicated that the compounds 6a, 6a-b, 6a-e, 6k, 6k-a and 6k-b showed remarkable
FXa inhibitory activity and excellent selectivity over thrombin in vitro.
Selected compounds also exhibited anticoagulant activities in vitro consequently
and were potent novel anti-coagulators in further.
PMID- 28415602
TI - ERRF sensitizes ERBB2-positive breast cancer cells to lapatinib treatment likely
by attenuating MCL1 and ERBB2 expression.
AB - Previously we found that the estrogen receptor (ER) related factor ERRF regulates
cell proliferation and tumor growth, and its expression is positively associated
with ER status and better survival but inversely associated with ERBB2 (also
named HER2) status in breast cancer. Here we report that ERRF also plays an
important role in the response of ERBB2-positive breast cancer cells to
lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR
pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF
expression correlated with lapatinib resistance, restoration of ERRF expression
in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib
responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK
BR-3 caused lapatinib resistance. ERRF-enhanced lapatinib sensitivity was also
confirmed in xenograft tumors of JIMT-1 cells. In patients with ERBB2-positive
breast cancer, higher level of ERRF expression correlated with both pathologic
complete response (pCR) to lapatinib and better survival. Mechanistically, ERRF
expression in resistant cells promoted lapatinib-induced apoptosis by attenuating
MCL1 and ERBB2 expression. These results suggest that ERRF plays an important
role in lapatinib response of ERBB2-positive breast cancer, and further study of
ERRF could lead to improved prediction and sensitivity of lapatinib response.
PMID- 28415605
TI - KIFC1 is essential for acrosome formation and nuclear shaping during
spermiogenesis in the lobster Procambarus clarkii.
AB - In order to study the function of kinesin-14 motor protein KIFC1 during
spermatogenesis of Procambarus clarkii, the full length of kifc1 was cloned from
testes cDNA using Rapid-Amplification of cDNA Ends (RACE). The deduced KIFC1
protein sequence showed the highest similarity between Procambarus clarkii and
Eriocheir senensis (similarity rate as 64%). According to the results of in situ
hybridization (ISH), the kifc1 mRNA was gathered in the acrosome location above
nucleus in the mid- and late-stage spermatids. Immunofluorescence results were
partly consistent with the ISH in middle spermatids, while in the late spermatids
the KIFC1 was distributed around the nucleus which had large deformation and
formed four to six nuclear arms. In the mature sperm, KIFC1 and microtubules were
distributed around the sperm, playing a role in maintaining the sperm morphology
and normal function. Overexpression of P. clarkii kifc1 in GC1 cells for 24 hours
resulted in disorganization of microtubules which changed the cell morphology
from circular and spherical into fusiform. In addition, the overexpression also
resulted in triple centrosomes during mitosis which eventually led to cell
apoptosis. RNAi experiments showed that decreased KIFC1 protein levels resulted
in total inhibition of spermatogenesis, with only mature sperm found in the RNAi
testis, implying an indispensable role of KIFC1 during P. clarkii spermiogenesis.
PMID- 28415604
TI - Inhibiting G protein betagamma signaling blocks prostate cancer progression and
enhances the efficacy of paclitaxel.
AB - Aberrant activation of G protein-coupled receptors (GPCRs) is implicated in
prostate cancer progression, but targeting them has been challenging because
multiple GPCRs are involved in cancer progression. In this study, we tested the
effect of blocking signaling via a hub through which multiple GPCRs converge -
the G-protein Gbetagamma subunits. Inhibiting Gbetagamma signaling in several
castration-resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1),
impaired cell growth and migration in vitro, and halted tumor growth and
metastasis in nude mice. The blockade of Gbetagamma signaling also diminished
prostate cancer stem cell-like activities, by reducing tumorsphere formation in
vitro and tumor formation in a limiting dilution assay in nude mice. Furthermore,
Gbetagamma blockade enhanced the sensitivity of prostate cancer cells to
paclitaxel treatment, both in vitro and in vivo. Together, our results identify a
novel function of Gbetagamma in regulating prostate cancer stem-cell-like
activities, and demonstrate that targeting Gbetagamma signaling is an effective
approach in blocking prostate cancer progression and augmenting response to
chemotherapy.
PMID- 28415606
TI - TAZ induces lung cancer stem cell properties and tumorigenesis by up-regulating
ALDH1A1.
AB - Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in
lung cancer. Therefore, identification of lung CSC drivers may provide promising
targets for lung cancer. TAZ is a transcriptional co-activator and key downstream
effector of the Hippo pathway, which plays critical roles in various biological
processes. TAZ has been shown to be overexpressed in lung cancer and involved in
tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for
lung CSCs and tumor formation in vivo is unknown. In addition, the molecular
mechanism underlying TAZ-induced lung tumorigenesis remains to be determined. In
this study, we provided evidence that constitutively active TAZ (TAZ-S89A) is a
driver for lung tumorigenesis in vivo in mice and formation of lung CSC. Further
RNA-seq and qRT-PCR analysis identified Aldh1a1, a well-established CSC marker,
as critical TAZ downstream target and showed that TAZ induces Aldh1a1
transcription by activating its promoter activity through interaction with the
transcription factor TEAD. Most significantly, inhibition of ALDH1A1 with its
inhibitor A37 or CRISPR gene knockout in lung cancer cells suppressed lung
tumorigenic and CSC phenotypes in vitro, and tumor formation in mice in vivo. In
conclusion, this study identified TAZ as a novel inducer of lung CSCs and the
first transcriptional activator of the stem cell marker ALDH1A1. Most
significantly, we identified ALDH1A1 as a critical meditator of TAZ-induced
tumorigenic and CSC phenotypes in lung cancer. Our studies provided preclinical
data for targeting of TAZ-TEAD-ALDH1A1 signaling to inhibit CSC-induced lung
tumorigenesis in the future.
PMID- 28415607
TI - Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA
hypermethylation reversal in leukemia cells.
AB - Thymoquinone (TQ), a bioactive constituent of the volatile oil of Monarda
fistulosa and Nigella sativa, possesses cancer-specific growth inhibitory
effects, but the underlying molecular mechanisms remain largely elusive. We
propose that TQ curbs cancer cell growth through dysfunction of DNA
methyltransferase 1 (DNMT1). Molecular docking analysis revealed that TQ might
interact with the catalytic pocket of DNMT1 and compete with co-factor SAM/SAH
for DNMT1 inhibition. In vitro inhibitory assays showed that TQ decreases DNMT1
methylation activity in a dose-dependent manner with an apparent IC50 of 30 nM.
Further, exposure of leukemia cell lines and patient primary cells to TQ resulted
in DNMT1 downregulation, mechanistically, through dissociation of Sp1/NFkB
complex from DNMT1 promoter. This led to a reduction of DNA methylation, a
decrease of colony formation and an increase of cell apoptosis via the activation
of caspases. In addition, we developed and validated a sensitive and specific LC
MS/MS method and successfully detected a dynamic change of TQ in mouse plasma
after administration of TQ through the tail vein, and determined a tolerable dose
of TQ to be 15 mg/kg in mouse. TQ administration into leukemia-bearing mice
induced leukemia regression, as indicated by the reversed splenomegaly and the
inhibited leukemia cell growth in lungs and livers. Our study for the first time
demonstrates that DNMT1-dependent DNA methylation mediates the anticancer actions
of TQ, opening a window to develop TQ as a novel DNA hypomethylating agent for
leukemia therapy.
PMID- 28415608
TI - Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1)
produced in cancer cells promote tumor budding at the invasion front in human
urothelial carcinoma of the bladder.
AB - Current knowledge of the molecular mechanism driving tumor budding is limited.
Here, we focused on elucidating the detailed mechanism underlying tumor budding
in urothelial cancer of the bladder. Invasive urothelial cancer was
pathologically classified into three groups as follows: nodular, trabecular, and
infiltrative (tumor budding). Pathohistological analysis of the orthotopic tumor
model revealed that human urothelial cancer cell lines MGH-U3, UM-UC-14, and UM
UC-3 displayed typical nodular, trabecular, and infiltrative patterns,
respectively. Based on the results of comprehensive gene expression analysis
using microarray (25 K Human Oligo chip), we identified two collagens, COL4A1 and
COL13A1, which may contribute to the formation of the infiltrative pattern.
Visualization of protein interaction networks revealed that proteins associated
with connective tissue disorders, epithelial-mesenchymal transition, growth
hormone, and estrogen were pivotal factors in tumor cells. To evaluate the
invasion pattern of tumor cells in vitro, 3-D collective cell invasion assay
using Matrigel was performed. Invadopodial formation was evaluated using Gelatin
Invadopodia Assay. Knockdown of collagens with siRNA led to dramatic changes in
invasion patterns and a decrease in invasion capability through decreased
invadopodia. The in vivo orthotopic experimental model of bladder tumors showed
that intravesical treatment with siRNA targeting COL4A1 and COL13A1 inhibited the
formation of the infiltrative pattern. COL4A1 and COL13A1 production by cancer
cells plays a pivotal role in tumor invasion through the induction of tumor
budding. Blocking of these collagens may be an attractive therapeutic approach
for treatment of human urothelial cancer of the bladder.
PMID- 28415609
TI - Identification of driver modules in pan-cancer via coordinating coverage and
exclusivity.
AB - It is widely accepted that cancer is driven by accumulated somatic mutations
during the lifetime of an individual. Cancer mutations may target relatively
small number of cell functional modules. The heterogeneity in different cancer
patients makes it difficult to identify driver mutations or functional modules
related to cancer. It is biologically desired to be capable of identifying cancer
pathway modules through coordination between coverage and exclusivity. There have
been a few approaches developed for this purpose, but they all have limitations
in practice due to their computational complexity and prediction accuracy. We
present a network based approach, CovEx, to predict the specific patient oriented
modules by 1) discovering candidate modules for each considered gene, 2)
extracting significant candidates by harmonizing coverage and exclusivity and, 3)
further selecting the patient oriented modules based on a set cover model.
Applying CovEx to pan-cancer datasets spanning 12 cancer types collecting from
public database TCGA, it demonstrates significant superiority over the current
leading competitors in performance. It is published under GNU GENERAL PUBLIC
LICENSE and the source code is available at:
https://sourceforge.net/projects/cancer-pathway/files/.
PMID- 28415610
TI - The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS
accumulation and activation of FOXO3 in neuroblastoma.
AB - Neuroblastoma is the most frequent extra-cranial solid tumor in children with
still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as
a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477
induces death in neuroblastoma cells independent of PKB-activation status and
stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that
finally leads to cell death associated with mitotic catastrophe. Autophagy is
critical for MG-2477-induced death and is regulated by the BH3-only protein
PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby
displaces and activates the autophagy-regulator BECN1/beclin1. Knockdown of NOXA
or overexpression of its pro-survival binding partners MCL1 and BCLXL counteracts
MG-2477-induced cell death. MG-2477 also rapidly induces the repression of the
anti-apoptotic protein Survivin, which promotes autophagy and cell death. We
further observed the accumulation of reactive oxygen species (ROS) that triggers
autophagy induction suggesting a change of the PI3 kinase-III/BECN1 complex and
activates the transcription factor FOXO3, which contributes to final cell death
induction. The combined data suggest that MG-2477 induces a sequential process of
ROS-accumulation, autophagy and FOXO3-activation that leads to cell death in
neuroblastoma cells.
PMID- 28415616
TI - Z-ligustilide restores tamoxifen sensitivity of ERa negative breast cancer cells
by reversing MTA1/IFI16/HDACs complex mediated epigenetic repression of ERa.
AB - Emerging evidence indicates epigenetic modification represses estrogen receptor
alpha (ERalpha) and contributes to the resistance to tamoxifen in aggressive
ERalpha-negative (ERalpha-) breast cancer. Z-ligustilide is a major compound in
Radix Angelica sinensis, an herb from traditional Chinese medicine (TCM) most
frequently prescribed for breast cancer. However, the role of Z-ligustilide in
ERalpha- breast cancer and epigenetic modification remains largely unknown.
Herein we showed, for the first time, that Z-ligustilide restored the growth
inhibition of tamoxifen on ERalpha- breast cancer cells. Apoptosis and S and G2/M
phases cell cycle arrest were induced by combinatorial Z-ligustilide and
tamoxifen. Importantly, Z-ligustilide reactivated the ERalpha expression and
transcriptional activity, which is proved to be indispensable for restoring the
sensitivity to tamoxifen. Interestingly, Z-ligustilide increased Ace-H3 (lys9/14)
enrichment in the ERalpha promoter. Moreover, Z-ligustilide dramatically reduced
the enrichment of metastasis-associated protein 1 (MTA1) as well as IFN-gamma
inducible protein 16 (IFI16) and histone deacetylases (HDACs) onto the ERalpha
promoter. Meanwhile, Z-ligustilide downregulated MTA1, IFI16 and HDACs, which
caused destabilization of the corepressor complex. Collectively, our study not
only highlights Z-ligustilide as a novel epigenetic modulator, but also opens new
possibilities from TCM for treating aggressive tamoxifen-resistant breast cancer.
PMID- 28415618
TI - Circular RNA alterations are involved in resistance to avian leukosis virus
subgroup-J-induced tumor formation in chickens.
AB - Avian leukosis virus subgroup (ALV-J) is an oncogenic neoplasm-inducing
retrovirus that causes significant economic losses in the poultry industry.
Recent studies have demonstrated circular RNAs (circRNAs) are implicated in
pathogenic processes; however, no research has indicated circRNAs are involved in
resistance to disease. In this study, over 1800 circRNAs were detected by circRNA
sequencing of liver tissues from ALV-J-resistant (n = 3) and ALV-J-susceptible
chickens (n = 3). 32 differentially expressed circRNAs were selected for
analyzing including 12 upregulated in ALV-J-resistant chickens and 20 upregulated
in ALV-J-susceptible chickens, besides, the top five microRNAs (miRNAs) for 12
upregulated circRNAs in ALV-J-resistant chickens were analyzed. Gene ontology and
KEGG pathway analyses were performed for miRNA target genes, the predicted genes
were mainly involved in immune pathways. This study provides the first evidence
that circRNA alterations are involved in resistance to ALV-J-induced tumor
formation. We propose circRNAs may help to mediate tumor induction and
development in chickens.
PMID- 28415619
TI - Association of two microRNA polymorphisms miR-27 rs895819 and miR-423 rs6505162
with the risk of cancer.
AB - Many studies have been conducted to investigate the association between miR-27
rs895819 A > G and miR-423 rs6505162 C > A and cancer risk; however, the results
are not consistent. In order to acquire a more precise assessment of the
correlation, we performed this meta-analysis. We searched PubMed, EMBASE and Web
of Science databases to identify eligible studies. Pooled odds ratios (ORs) and
95% confidence intervals (CIs) were applied to evaluate the correlation of these
two microRNA polymorphisms with cancer risk. Forty-five eligible studies from
thirty-five articles were included in our analysis. The results showed that
rs895819 was associated with a decreased cancer risk in Caucasians (AG vs. AA: OR
= 0.87, 95% CI = 0.79-0.96; GG+AG vs. AA: OR = 0.89, 95% CI = 0.81-0.98). When
grouped by ethnicity, an increased risk was observed in colorectal cancer (G vs.
A: OR = 1.19, 95% CI = 1.08-1.32; GG vs. AA: OR = 1.58, 95% CI = 1.28-1.96; GG
vs. AG+AA: OR = 1.58, 95% CI = 1.29-1.93), while a decreased risk was found in
breast cancer (G vs. A: OR = 0.93, 95% CI = 0.87-0.99; GG+AG vs. AA: OR = 0.91,
95% CI = 0.83-0.99). For rs6505162, a significantly decreased cancer risk was
observed in lung cancer under all five genetic models. To summarize, our results
indicated that rs895819 was a protective factor for cancer in Caucasians and
could increase colorectal cancer risk but decrease breast cancer risk. Moreover,
rs6505162 was a protective factor for lung cancer.
PMID- 28415621
TI - USP22 maintains gastric cancer stem cell stemness and promotes gastric cancer
progression by stabilizing BMI1 protein.
AB - Increased ubiquitin-specific protease 22 (USP22) has been associated with poor
prognosis in several cancers including gastric cancer. However, the role of USP22
in gastric tumorigenesis is still unclear. Gastric cancer stem cells have been
identified and shown to correlate with gastric cancer initiation and metastasis.
In this study, we found that silencing of USP22 inhibited proliferation of
gastric cancer cells and suppressed the cancer stem cell spheroid formation in
serum-free culture. Furthermore, cancer stem cell markers, such as CD133, SOX2,
OCT4 and NANOG were down-regulated. Additionally, knockdown of USP22 inhibited
gastric cancer xenografts growth. Our analysis of TCGA database indicated that
BMI1 overexpression may predict gastric cancer patient survival, and TAT-BMI1
proteins reversed the USP22 knockdown-mediated decreased in cancer stem cell
properties, and elevated the expression of stemness-associated genes.
Furthermore, we found that overexpression of USP22 stabilized the BMI1 protein in
gastric cancer cells. Taken together, our study demonstrates that USP22 is
indispensable for gastric cancer stem cell self-renewal through stabilization of
BMI1. These results may provide novel approaches to the theranostics of gastric
cancer in the near future.
PMID- 28415624
TI - Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular
smooth muscle cell through PI3K/AKT/AEG-1 signaling.
AB - To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG
1) have been involved in the proliferation, migration and morphological changes
of vascular smooth muscle cells. However, the potential relationship of HIF-1a
AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported.
In the present study, in-vitro assays were utilized to explore the potential
impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a
expression was up-regulated in the media of thoracic aortic dissection tissues as
compared with normal aortic tissues, and was associated with increased apoptotic
SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the
expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the
expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression.
Functionally, HIF-1a inhibited the proliferation and migration of HASMCs.
However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions
and biological effects above. In conclusion, HIF-1a induces HASMC phenotype
switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide
new avenues for the prevention and treatment of aortic dissection diseases.
PMID- 28415625
TI - Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through
Nrf2/ROS pathway.
AB - Seven cardenolides isolated from the ethanol extract of the stems of Calotropis
gigantea were evaluated in vitro against human cancer cells and the structure
activity relationships were discussed. The results demonstrated that a compound,
named CGN (coroglaucigenin), had better anti-proliferative activity with the IC50
value less than 6 MUM among these compounds. Further, we found that CGN displayed
much lower cytotoxicity to normal lung epithelial cells (BEAS-2B) than cancer
cells (A549). Especially, our results demonstrated that treatment with CGN (1
MUM) combined with X-ray irradiation induced higher radiosensitivity in human
lung cancer cells (A549, NCI-H460, NCI-H446) but not in BEAS-2B. The expression
levels of nuclear transcription factor Nrf2 and Nrf2-driven antioxidant molecule
NQO-1 reduced in A549 cells after combined treatment compared to the radiation
only. However, CGN had no toxicity and the levels of antioxidant molecules
expression were higher in BEAS-2B cells when given the similar treatment as A549
cells. These results suggest that CGN is a very promising potential sensitizer
for cancer radiotherapy, which not only inhibits the proliferation of cancer
cells but also enhances the radiosensitivity of cancer cells through suppressing
the expression of antioxidant molecules while there is no influence for normal
cells.
PMID- 28415626
TI - Hematopoietic stem/progenitor cells are less prone to undergo apoptosis than
lymphocytes despite similar DNA damage response.
AB - Hematopoietic stem/progenitor CD34+ cells (HSPC) give rise to all types of blood
cells and represent a key cellular target for origination of leukemia. Apoptosis
and repair of DNA double strand breaks (DSB) are vital processes in
leukemogenesis. High doses of ionizing radiation are the best known agent that
induces leukemia, but less is known about the leukemogenic potential of low
doses. While umbilical cord blood (UCB) serves as a valuable source of the HSPC
for both research and clinics, the data on DNA damage response and apoptosis in
UCB HSPC are very limited. We have studied apoptosis and DSB in the UCB-derived
CD34+HSPC and CD34- lymphocytes at different time points post-irradiation with
low and therapeutic doses of gamma-rays. DSB were enumerated with gammaH2AX foci
using imaging flow cytometry. Different stages of apoptosis were analyzed using
Annexin/7-AAD assay and gammaH2AX pan-staining by flow cytometry and imaging flow
cytometry, respectively. Our results have consistently shown significantly higher
resistance of CD34+ stem/progenitor cells to endogenous and radiation induced
apoptosis as compared to CD34- lymphocytes. At the same time, no statistically
significant difference was found in DSB repair between HSPC and lymphocytes as
enumerated by the gammaH2AX foci. To conclude, we show for the first time that
hematopoietic stem/progenitor cells are less prone to undergo apoptosis than
lymphocytes what may be accounted for higher expression of anti-apoptotic
proteins in CD34+ cells but was unlikely dealt with DSB repair.
PMID- 28415627
TI - Importance of the plasma soluble HLA-G levels for prognostic stratification with
traditional prognosticators in colorectal cancer.
AB - An increased peripheral soluble HLA-G (sHLA-G) expression has been observed in
various malignancies while its prognostic significance was rather limited. In
this study, the prognostic value of plasma sHLA-G in 178 colorectal cancer (CRC)
patients was investigated. sHLA-G levels were analyzed by specific enzyme-linked
immunosorbent assay. Data showed sHLA-G levels were significantly increased in
CRC patients compared with normal controls (36.8 U/ml vs 25.4 U/ml, p = 0.009).
sHLA-G in the died were obviously higher than that of alive CRC patients (46.8
U/ml vs 27.4 U/ml, p = 0.012). Patients with sHLA-G above median levels (>= 36.8
U/ml, sHLA-Ghigh) had a significantly shorter survival time than those with sHLA
Glow (< 36.8 U/ml, p < 0.001), and sHLA-G could be an independent prognostic
factor for CRC patients. With stratification of clinical parameters in survival
by sHLA-Glow and sHLA-Ghigh, sHLA-G exhibited a significant predictive value for
CRC patients of the female (p = 0.036), the elder (p = 0.009), advanced tumor
burden (T3 + 4, p = 0.038), regional lymph node status (N0, p = 0.041), both
metastasis status (M0, p = 0.014) and (M1, p=0.018), and clinical stage (I + II,
p = 0.018), respectively. Summary, our data demonstrated for the first time that
sHLA-G levels is an independent prognosis factor and improves the prognostic
stratification offered by traditional prognosticators in CRC patients.
PMID- 28415628
TI - Gut microbiota drives the attenuation of dextran sulphate sodium-induced colitis
by Huangqin decoction.
AB - The gut microbiota, including probiotics and pathogenic microorganisms, is
involved in ulcerative colitis (UC) by regulating pathogenic microorganisms and
the production of intestinal mucosal antibodies. Huangqin decoction (HQD), a
traditional Chinese formula chronicled in the Shanghan lun, has been recognized
as an effective drug for UC, owing to its anti-inflammatory and anti-oxidative
properties. In the present study, we investigated whether HQD ameliorates dextran
sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota.
We found that HQD significantly inhibited colitis, alleviating the loss of body
weight, disease activity index, colon shortening, tissue injury, and inflammatory
cytokine changes induced by DSS treatment. Principal component analysis and
principal co-ordinate analysis showed an obvious difference among the groups,
with increased diversity in the DSS and DSS+HQD groups. Linear discriminant
analysis effect size was used to determine differences between the groups. The
relative abundance of Lactococcus was higher in the DSS+HQD group than in the DSS
group, whereas Desulfovibrio and Helicobacter were decreased. Furthermore, the
protective effect of HQD was attenuated only in antibiotic-treated mice. In
conclusion, our results suggest that HQD could ameliorate DSS-induced
inflammation through alteration of the gut microbiota.
PMID- 28415629
TI - A(H1N1)pdm09 influenza infection: vaccine inefficiency.
AB - The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus,
began in North America at 2009. Since then, the World Health Organization (WHO)
recommended integration of the swine-based virus A/California/07/2009 strain in
yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in
subsequent years. The reasons for this are currently unknown. During the 2015
2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza
virus infection in Israel. Our phylogenetic analysis indicated that the
circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed
from the vaccinating strain, with approximately 18 amino acid differences found
between the circulating strains and the immunizing A/California/07/2009 strain.
Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer
against the A/California/07/2009 vaccinating strain as compared to the
circulating Israeli strains. We thus suggest that the current vaccination was not
sufficiently effective and propose inclusion of the current circulating
A(H1N1)pdm09 influenza viruses in the annual vaccine composition.
PMID- 28415630
TI - Resveratrol alleviates FFA and CCl4 induced apoptosis in HepG2 cells via
restoring endoplasmic reticulum stress.
AB - Cell apoptosis often induces inflammation and injury in the liver, with
endoplasmic reticulum (ER) stress as the most possible reason. Resveratrol (RSV)
has been shown to prevent hepatic steatosis and alleviate apoptosis, however, the
exact mechanisms underlying the effects still need to be explored. Here we co
cultured HepG2 cells with free fatty acid (FFA) solution (oleic acid: palmitic
acid = 2:1) and then exposed to a carbon tetrachloride (CCl4) solution to induce
apoptosis. To evaluate the therapeutic effects, RSV (2.5 MUM, 5 MUM, 10 MUM) was
added to the cells. Results showed that HepG2 cells co-cultured with FFA
exhibited lipid infiltration and were susceptible to apoptosis upon exposure to
the CCl4 solution. The expression of molecules related to apoptosis (Caspases,
Bcl-2/Bax) and ER stress (GRP78, IRE1, ATF6, PERK, et al.) was all significantly
decreased upon RSV treatment. We further inhibited GRP78 by siRNA, results showed
that the anti-apoptotic effect of RSV still maintained under GRP78 siRNA
condition. Our data demonstrated that lipid accumulated HepG2 cells were
susceptible to injury, and RSV could improve apoptosis in FFA and CCl4 stressed
cells, which partially via restoring ER function.
PMID- 28415631
TI - LncRNA HOTAIR acts a competing endogenous RNA to control the expression of notch3
via sponging miR-613 in pancreatic cancer.
AB - Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Though
studies have implicated the roles of microRNAs in pancreatic cancer progression,
little is known about the role of miR-613 in pancreatic cancer. In the present
study, the expression of miR-613 was down-regulated in pancreatic cancer tissues
and cancer cell lines. Down-regulation of miR-613 was positively correlated with
tumor differentiation, advanced TNM stage, nodal metastasis and shorter overall
survival in patients with pancreatic cancer. Overexpression of miR-613 suppressed
cell proliferation, invasion and migration, and induced cell apoptosis and cell
cycle arrest at G0/G1 phase in pancreatic cancer cells. Bioinformatics analysis,
luciferase reporter assay and rescue experiments showed that notch3 was a direct
target of miR-613. MiR-613 was inversely correlated with notch3 expression in
pancreatic cancer tissues. The long non-coding RNA, HOX transcript antisense RNA
(HOTAIR) was up-regulated in both pancreatic cancer tissues and cancer cell
lines, and HOTAIR suppressed the expression of miR-613 via functioning as a
competing endogenous RNA. In vivo studies showed that stable overexpression of
miR-613 or knock-down of HOTAIR suppressed tumor growth and also reduced the
expression of notch3. In conclusion, these results suggest that HOTAIR functions
as a competing endogenous RNA to regulate notch3 expression via sponging miR-613
in pancreatic cancer.
PMID- 28415632
TI - The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive
and castration-resistant prostate cancer cells.
AB - PURPOSE OF THE STUDY: Reduced levels of the tumor suppressor protein CCDC6
sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of
CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the
androgen receptor (AR) stability. Here, we correlated the expression levels of
CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the
efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel
therapeutic option in advanced prostate cancer.Experimental techniques: PC cells
were exposed to USP7 inhibitor, P5091, together with cycloheximide, to
investigate the turnover of the USP7 substrates, AR and CCDC6. As outcome of the
AR downregulation, transcription targets of AR and its variant V7 were examined
by qPCR. As a result of CCDC6 degradation, the induction of PARP inhibitors
sensitivity was evaluated by analyzing PC cells viability and foci formation. We
scored and correlated CCDC6 and USP7 expression levels in a prostate cancer
tissue microarray (TMA). RESULTS: P5091 accelerated the degradation of AR and V7
isoform affecting PSA, UBE2C, CDC20 transcription and PC cells proliferation.
Moreover, P5091 accelerated the degradation of CCDC6 sensitizing the cells to
PARP-inhibitors, that acted sinergistically with genotoxic agents. The
immunohistochemical analysis of both CCDC6 and USP7 proteins exhibited
significant correlation for the intensity of staining (p <= 0.05).Data
interpretation: Thus, CCDC6 and USP7 represent predictive markers for the
combined treatment of the USP7-inhibitors and PARP-inhibitors in advanced
prostate cancer.
PMID- 28415633
TI - A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic
adenoid cystic carcinoma.
AB - PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a
confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient
treated with vorinostat in a prior phase 1 trial, we initiated this phase 2
trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles.
The primary objective was to evaluate response rate (RR). Exploratory studies
included whole exome sequencing (WES) of selected patients. RESULTS: Thirty
patients were enrolled. Median age of patients was 53 years (range 21-73). Median
number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3),
oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the
only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven
patients were dose reduced secondary to drug-related AEs. Two patients had a
partial response (PR), with response durations of 53 and 7.2 months. One patient
had a minor response with a decrease in ascites (for 19 cycles). Stable disease
was the best response in 27 patients. Targeted and WES of 8 patients in this
trial identified mutations in chromatin remodeling genes highlighting the role of
the epigenome in ACC. CONCLUSION: Vorinostat demonstrated efficacy in patients
with ACC supporting the inclusion of HDACi in future studies to treat ACC.
PMID- 28415634
TI - A meta-analysis of randomized controlled trials comparing the efficacy and safety
of anastrozole versus tamoxifen for breast cancer.
AB - Whether anastrozole has superior effects to tamoxifen for breast cancer remains
controversial. Therefore, we conducted this meta-analysis of randomized
controlled trials (RCTs) to compare the efficacy and safety of anastrozole versus
tamoxifen as adjuvant therapy in breast cancer. A systematic literature search of
PubMed, Web of Science, Embase, and Cochrane library were performed to evaluate
the survival benefits and toxicity profiles of patients with breast cancer who
were treated with anastrozole or tamoxifen. The main outcome measures included
disease-free survival (DFS), recurrence-free survival (RFS), overall survival
(OS), overall response rate (ORR), and adverse events. Hazard ratios (HRs) or
risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a fixed
effects model or random-effects model. Nine RCTs with a total of 15,300 patients
met the inclusion criteria and were included in this meta-analysis. Pooled
estimates suggested that, anastrozole was associated with a significantly
improvement in DFS (HR=0.72, 95%CI: 0.55-0.94; P=0.016), and ORR (RR=1.21, 95%
CI: 1.05-1.39; P=0.009) than tamoxifen. But it did not prolong OS (HR=0.96,
95%CI: 0.77-1.21; P=0.751). Compared with tamoxifen, anastrozole induced a higher
incidence of arthralgia (RR=1.55, 95%CI: 1.20-1.99; P=0.001) and bone pain
(RR=1.31, 95%CI: 1.05-1.62; P=0.015), as well as a lower incidence of vaginal
bleeding (RR=0.51, 95%CI: 0.28-0.93; P=0.029), vaginal discharge (RR=0.31, 95%CI:
0.12-0.82; P=0.017), and thromboembolic events (RR=0.39, 95%CI: 0.28-0.55;
P<0.001). Based on the current evidence, patients with breast cancer would
benefit from the anastrozole treatment.
PMID- 28415636
TI - Comparison of combined leflunomide and low-dose corticosteroid therapy with full
dose corticosteroid monotherapy for progressive IgA nephropathy.
AB - IgA nephropathy is the most common primary glomerulonephritis and one of the
leading causes of end-stage renal disease. We performed a randomized, controlled,
prospective, open-label trial to determine whether leflunomide combined with low
dose corticosteroid is safe and effective for the treatment of progressive IgA
nephropathy, as compared to full-dose corticosteroid monotherapy. Biopsy-proved
primary IgA nephropathy patients with an estimated glomerular filtration rate >=
30 ml/min/1.73m2 and proteinuria >=1.0 g/24h were randomly assigned to receive
leflunomide+low-dose corticosteroid (leflunomide group; n = 40) or full-dose
corticosteroid (corticosteroids group; n = 45). The primary outcome was renal
survival; secondary outcomes were proteinuria and adverse events. After 12 months
of treatment and an average follow-up of 88 months, 11.1% vs. 7.5% of patients
reached end-stage renal disease and 20% versus 10% of patients had a >= 50%
increase in serum creatinine in the corticosteroids and leflunomide groups,
respectively. Kaplan-Meier analysis did not reveal a between-group difference in
these outcomes. Decreases in 24-hour proteinuria were similar in the two groups
during the treatment period, but a more marked reduction was observed during
follow-up in the leflunomide group. Although the incidence of adverse events was
similar in the two groups, serious adverse events were observed only in the
corticosteroid group. Thus, leflunomide combined with low-dose corticosteroid is
at least as effective as corticosteroid alone for the treatment of progressive
IgA nephropathy, and showed a greater reduction of proteinuria during long-term
follow-up and fewer severe adverse events.
PMID- 28415635
TI - Role of EZH2 in cancer stem cells: from biological insight to a therapeutic
target.
AB - Epigenetic modifications in cancer stem cells largely result in phenotypic and
functional heterogeneity in many solid tumors. Increasing evidence indicates that
enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor
complex 2, is highly expressed in cancer stem cells of numerous malignant tumors
and has a critical function in cancer stem cell expansion and maintenance. Here,
we review up-to-date information regarding EZH2 expression patterns, functions,
and molecular mechanisms in cancer stem cells in various malignant tumors and
discuss the therapeutic potential of targeting EZH2 in tumors.
PMID- 28415638
TI - Altered long non-coding RNAs predict worse outcome in osteosarcoma patients:
evidence from a meta-analysis.
AB - Long non-coding RNAs (lncRNAs) are emerging as promising prognostic biomarkers in
an expanding list of malignant neoplasms. Here, we sought to investigate the
strength of associations between lncRNA signatures and clinical outcomes in
osteosarcoma. We conducted a systematic search of the online databases from
inception to July 2016. Hazard ratios (HRs) with corresponding 95% confidence
intervals (CIs) for the primary endpoints of overall survival (OS), progression
free survival (PFS) or event-free survival (EFS) were extracted and meta
analyzed. Our results manifested that altered lncRNAs expression was markedly
associated with worse OS (univariate analysis: HR = 3.20, 95% CI: 2.42-4.24, P =
0.000; multivariate analysis: HR = 2.66, 95% CI: 1.92-3.69, P = 0.000), PFS (HR =
2.05, 95% CI: 1.32-3.18, P = 0.001) and EFS (HR = 4.37, 95% CI: 1.64-11.66, P =
0.003) times among osteosarcoma patients. In the pooled analyses stratified by
clinicopathological features, levels of lncRNAs were closely correlated with
tumor size (pooled P = 0.001), tumor stage (pooled P = 0.003), and distant
metastasis (pooled P = 0.002) in osteosarcoma. The results obtained in our work
suggest that altered lncRNA signatures predict unfavorable clinical outcomes and
are acceptable to be potential prognostic biomarkers in forecasting prognosis of
osteosarcoma.
PMID- 28415639
TI - Epithelial-to-mesenchymal transition in the development of endometriosis.
AB - Endometriosis, an estrogen-dependent chronic gynecological disease, is common in
reproductive-age women and profoundly affects their life quality. Although
various pathogenic theories have been proposed, the origin of endometriosis
remains unclear. Epithelial to mesenchymal transition (EMT) is a process that
epithelial cells lose polarized organization of the cytoskeleton and cell-to-cell
contacts, acquiring the high motility of mesenchymal cells. These changes are
thought to be prerequisites for the original establishment of endometriotic
lesions. However, no study exactly indicates which type of EMT occurs in
endometriosis. In this review, we conclude that two different types of EMT may
participate in this disease. Besides, two stimulating signals, hypoxia and
estrogen, can through different pathways to activate the EMT process in
endometriosis. Those pathways involve many cellular factors such as TGF-beta and
Wnt, ultimately leading to cell proliferation and migration. As infertility is
becoming a serious and intractable issue for women, EMT, during the implantation
process, is gaining attention. In this review, we will describe the known
functions of EMT in endometriosis, and suggest further studies that may aid in
the development of medical therapy.
PMID- 28415640
TI - Accuracy of the urine UCA1 for diagnosis of bladder cancer: a meta-analysis.
AB - Urine UCA1 has been reported as a potential novel diagnostic biomarker for
bladder cancer in several studies, but their results are inconsistent. As a
result of this, a diagnostic meta-analysis to assess the diagnostic performance
of urine UCA1 in detecting bladder cancer was conducted. A systematic electronic
and manual search was performed for relevant literatures through PubMed, Cochrane
library, Chinese Wan Fang and the China National Knowledge Infrastructure (CNKI)
databases up to December 30, 2016. The quality of the studies included in this
meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy
Studies (QUADAS-2) tool. All analyses were conducted using stata12.0 software.
Six studies collectively included 578 bladder cancer patients and 562 controls
met the eligible criteria. The overall diagnostic accuracy was measured by the
following: sensitivity 0.81 (95% CI = 0.75-0.86), specificity 0.86 (95% CI = 0.73
0.93), positive likelihood ratio 5.85 (95% CI = 2.72-12.57), negative likelihood
0.22 (95% CI = 0.15-0.32), diagnostic odds ratio 27.01 (95% CI = 8.69-83.97), and
area under the curve 0.88 (95% CI = 0.85-0.91). Meta-regression analysis
suggested that ethnicity significantly accounted for the heterogeneity of
sensitivity. Deeks' funnel plot asymmetry test (P = 0.33) suggested no potential
publication bias. According to our results, urine UCA1 has greater diagnostic
value in diagnosing bladder cancer, however further research studies with more
well-designed and large sample sizes are required to confirm our findings.
PMID- 28415643
TI - New transcriptional-based insights into the pathogenesis of desmoplastic small
round cell tumors (DSRCTs).
AB - To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means
of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical
specimens obtained from seven pretreated DSRCT patients were interrogated using
GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in
situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and
miRNA-34/SLUG. The chimera modules divided the cases into three classes that
respectively recapitulated the traits of mesenchymal epithelial reverse
transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial
EMT. This indicates a close correlation between the reprogramming governed by EMT
regulators and DSRCT biology, which was further confirmed by miRNA-21 and is
consistent with the broad morphological spectrum of DSRCTs. Starting from the
miRNA-200/ZEB1 axis, we also found that DSRCTs carry a signature of immunological
ignorance that is not responsive to PD--L1 blockade. Evidence that the up
regulation of miRNA-200 and E-cadherin, and quite a high level of miRNA-21
expression segregate with the MErT supports the idea that, in addition to the
hybrid/partial state, MErT is also enriched in stemness: the androgen-positive
cases, whose stemness traits were confirmed by stem cell arrays, all fell into
these two classes. Our findings also confirmed that tumoral cell PDGFRA
expression correlates with desmoplasia, and demonstrated the co-expression of
PDGFRA and ISLR/Meflin, another marker of pluripotency. Despite the limited
number of cases, these findings provide unexpectedly relevant information
concerning the pathogenesis of DSRCTs, and prove the validity of miRNA-based
chimera circuit modelling in the clinico-pathological setting.
PMID- 28415641
TI - Identification and screening of effective protective antigens for channel catfish
against Streptococcus iniae.
AB - Vaccination is a potential approach for prevention and control of disease in
fish. The use of genetically engineered vaccines is an effective method and a
green intervention to control bacterial infection in aquaculture. However,
efforts to develop these vaccines are limited by the lack of conserved protective
antigens. In this study, three candidate immunogens (Srr, NeuA, and Hsp) of the
pathogenic Streptococcus iniae strain DGX07 isolated from diseased channel
catfish were identified and analyzed. Molecular cloning, expression, and
purification of candidate antigen genes were carried out to obtain the candidate
immunogens in the form of recombinant subunit vaccines. Western blotting was
performed to evaluate immunogenicity in vitro and channel catfish were vaccinated
by intraperitoneal injection and the specific antibody titers and relative
percent of survival were determined to evaluate immune protection in vivo. The
results showed that these three candidate immunogens were expressed correctly as
recombinant proteins fused with His tags, with molecular weights of 70 kDa for
Srr, 86 kDa for NeuA, and 51 kDa for Hsp, respectively. Moreover, each immunogen
was predicted to be located either extracellularly or on the surface of S. iniae,
and were able to offer protection against S. iniae infection in the form of
recombinant subunit vaccines with adjuvant ISA763, especially Srr, with a
relative percent of survival of 70% for Srr, 55% for NeuA, and 50% for Hsp,
respectively.
PMID- 28415644
TI - Long non-coding RNAs in cutaneous melanoma: clinical perspectives.
AB - Metastatic melanoma of the skin has a high mortality despite the recent
introduction of targeted therapy and immunotherapy. Long non-coding RNAs
(lncRNAs) are defined as transcripts of more than 200 nucleotides in length that
lack protein-coding potential. There is growing evidence that lncRNAs play an
important role in gene regulation, including oncogenesis. We present 13 lncRNA
genes involved in the pathogenesis of cutaneous melanoma through a variety of
pathways and molecular interactions. Some of these lncRNAs are possible
biomarkers or therapeutic targets for malignant melanoma.
PMID- 28415646
TI - Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11
translocation RCC: comparison of three different diagnostic methods.
AB - We evaluated the frequency of translocation renal cell carcinoma (RCC) by reverse
transcription polymerase chain reaction (RT-PCR) and how well the TFE3
immunoreactivity is concordant with TFE3 gene translocation status proved by
fluorescence in situ hybridization (FISH) assay and RT-PCR. TFE3 and Cathepsin K
expression was analyzed by immunohistochemistry in 185 RCC cases, and 48 cases
either of more than weak expression of TFE3 or of positivity for Cathepsin K were
done for FISH analysis and RT-PCR. All the RT-PCR positive cases were confirmed
by cloning and sequencing. Of the 14 cases with strong nuclear TFE3 expression,
12 showed a break-apart signal by FISH. ASPL- and PRCC-TFE3 translocations were
detected in 13 and one case, respectively, by RT-PCR. Of 21 cases with weak TFE3
expression, five were translocation-positive by FISH. ASPL-, PRCC-, and PSF-TFE3
translocations were detected by RT-PCR (n=3, 3, and 1, respectively). All 13 TFE3
negative/cathepsin K-positive cases were negative by FISH and two each harbored
ASPL- and PRCC-TFE3 translocations that were detected by RT-PCR. A high rate of
TFE3 immunoreactivity (8.6%) was confirmed by RT-PCR (13.5%) and FISH (9.7%).
Higher translocation rate of RT-PCR means RT-PCR detected translocation in TFE3
weak expression group and only cathepsin K positive group more specifically than
FISH. Thus, RT-PCR would complement FISH analysis for detecting translocation RCC
with fusion partners.
PMID- 28415645
TI - Peritoneal carcinomatosis: limits of diagnosis and the case for liquid biopsy.
AB - Peritoneal Carcinomatosis (PC) is a late stage manifestation of several
gastrointestinal malignancies including appendiceal, colorectal, and gastric
cancer. In PC, tumors metastasize to and deposit on the peritoneal surface and
often leave patients with only palliative treatment options. For colorectal PC,
median survival is approximately five months, and palliative systemic therapy is
able to extend this to approximately 12 months. However, cytoreductive surgery
with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with a curative intent
is possible in some patients with limited tumor burden. In well-selected patients
undergoing complete cytoreduction, median survival has been reported as high as
63 month. Identifying patients earlier who are either at risk for, or who have
recently developed PC may provide them with additional treatment options such as
CRS/HIPEC. PC is diagnosed late by imaging findings or often times during an
invasive procedures such as laparoscopy or laparotomy. In order to improve the
outcomes of PC patients, a minimally invasive, accurate, and specific PC
screening method needs to be developed. By utilizing circulating PC biomarkers in
the serum of patients, a "liquid biopsy," may be able to be generated to allow a
tailored treatment plan and early intervention. Exosomes, stable patient-derived
nanovesicles present in blood, urine, and many other bodily fluids, show promise
as a tool for the evaluation of labile biomarkers. If liquid biopsies can be
perfected in PC, manifestations of this cancer may be more effectively treated,
thus offering improved survival.
PMID- 28415649
TI - An epigenetic master regulator teams up to become an epioncogene.
PMID- 28415647
TI - Contrast agents in dynamic contrast-enhanced magnetic resonance imaging.
AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive
method to assess angiogenesis, which is widely used in clinical applications
including diagnosis, monitoring therapy response and prognosis estimation in
cancer patients. Contrast agents play a crucial role in DCE-MRI and should be
carefully selected in order to improve accuracy in DCE-MRI examination. Over the
past decades, there was much progress in the development of optimal contrast
agents in DCE-MRI. In this review, we describe the recent research advances in
this field and discuss properties of contrast agents, as well as their advantages
and disadvantages. Finally, we discuss the research perspectives for improving
this promising imaging method.
PMID- 28415650
TI - A highly conserved redox-active Mx(2)CWx(6)R motif regulates Zap70 stability and
activity.
AB - zeta-associated protein of 70 kDa (Zap70) is crucial for T-cell receptor (TCR)
signaling. Loss of Zap70 in both humans and mice results in severe
immunodeficiency. On the other hand, the expression of Zap70 in B-cell
malignancies correlates with the severity of the disease. Because of its role in
immune-related disorders, Zap70 has become a therapeutic target for the treatment
of human diseases. It is well-established that the activity/expression of Zap70
is regulated by post-translational modifications of crucial amino acids including
the phosphorylation of tyrosines and the ubiquitination of lysines. Here, we have
investigated whether also oxidation of cysteine residues regulates Zap70
functions. We have identified C575 as a major sulfenylation site of Zap70. A
C575A substitution results in protein instability, reduced activity, and
increased dependency on the Hsp90/Cdc37 chaperone system. Indeed, Cdc37
overexpression reconstituted partially the expression but fully the function of
Zap70C575A. C575 lies within a Mx(2)CWx(6)R motif which is highly conserved among
almost all human tyrosine kinases. Mutation of any of the conserved amino acids,
but not of a non-conserved residue preceding the cysteine, also results in Zap70
instability. Collectively, we have identified a new redox-active motif which is
crucial for the regulation of Zap70 stability/activity. We believe that this
motif has the potential to become a novel target for the development of
therapeutic tools to modulate the expression/activity of kinases.
PMID- 28415651
TI - Diabetes mellitus and the risk of gastric cancer: a meta-analysis of cohort
studies.
AB - Studies examining the relationship between diabetes mellitus (DM) and the risk of
gastric cancer incidence or gastric cancer mortality have produced inconsistent
results. The purpose of this study was to evaluate the evidence regarding the
relationship between DM and subsequent gastric cancer incidence or gastric cancer
mortality risk on the basis of cohort studies. A systematic search of articles in
PubMed, EmBase, the Cochrane Library, and reference lists was conducted to
identify relevant literature. Twenty-two cohort studies reporting data on
8,559,861 participants were included in the study. Overall, participants with DM
had little or no change in the risk of gastric cancer, or gastric cancer
mortality. There was no evidence of difference in the RR for gastric cancer
between men and women. Participants with DM had a non-significant trend towards
an increased risk of gastric cancer mortality in men. There was no significant
difference between men and women for this relationship. Finally, although
subgroup analysis suggested DM was associated with a significant impact on
gastric cancer incidence and gastric cancer mortality risk in several specific
populations, a significance based on gender difference was not observed. In
conclusion, DM might increase the risk of gastric cancer in men when the study
used standard incidence/mortality ratio as effect estimate. Further, DM were
associated with higher risk of gastric cancer mortality in men if the mean age at
baseline less than 55.0 years, used RR or HR as effect estimate, the study
adjusted smoking or not, and the study not adjusted alcohol drinking.
PMID- 28415653
TI - Association between HIF1A rs11549465 polymorphism and risk of prostate cancer: a
meta-analysis.
AB - The hypoxia inducible factor 1-alpha (HIF1A) gene has been suggested to play a
critical role in cancer progression, and the relationship between HIF1A
rs11549465 polymorphism and risk of prostate cancer has been investigated in
previous studies. Nevertheless, conflicting results have been obtained. Hence, we
reevaluated this issue by means of this meta-analysis, with the purpose of
providing more precise conclusion on this issue. The electronic databases of
PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) as well as
other sources were searched for relevant reports concerning on the role of HIF1A
rs11549465 polymorphism in the occurrence of prostate cancer. The strength of the
relationship was determined by calculating odds ratios (ORs) with corresponding
95% confidence intervals (95% CIs). Besides, subgroup analyses by ethnicity and
source of control were further performed to examine this relationship. All
statistical analyses were performed using STATA software 12.0. Although HIF1A
rs11549465 polymorphism showed a tendency of increasing the risk of prostate
cancer, no statistical significance was detected under any genetic models.
Similar results were also revealed in subgroup analyses on the basis of ethnicity
and control source. Our findings indicate that HIF1A rs11549465 polymorphism may
not independently play a significant role in the occurrence of prostate cancer.
PMID- 28415654
TI - The associations between the MAPT polymorphisms and Alzheimer's disease risk: a
meta-analysis.
AB - Published studies revealed that the microtubule-associated protein tau (MAPT)
gene polymorphisms increased Alzheimer's disease (AD) risk; the associations of 4
single nucleotide polymorphisms (SNPs, rs242557G/A, rs2471738C/T, rs3785883G/A
and rs1467967A/G) of the MAPT gene with AD risk, however, remain inconclusive.
Here, we conducted a meta-analysis to investigate the relationship between the
MAPT SNPs and AD risk. A significant association of SNP rs242557 with AD risk was
found in a dominant [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.01,
1.10, P = 0.025] genetic model, and a suggestive association in an allelic (OR =
1.03, 95% CI = 1.00, 1.06, P = 0.078). When APOE epsilon 4 carrier status was
included in stratified analysis, this association was even stronger (allelic
model for the APOE epsilon 4 positive individuals: OR = 1.24, 95% CI = 1.08,
1.43, P = 0.003). Furthermore, a significant association of SNP rs2471738 with AD
risk was found under all the four models (allelic: OR = 1.11, 95% CI = 1.01,
1.20, P = 0.021; dominant: OR = 1.10, 95% CI = 1.00, 1.21, P = 0.046; recessive:
OR = 1.18, 95% CI = 1.05, 1.32, P = 0.004; additive: OR = 1.20, 95% CI = 1.07,
1.34, P = 0.002) models. However, pooled results suggest that the neither
rs3785883 nor rs1467967 is associated with AD risk under all the four genetic
models. In summary, our study provides further evidence of the associations of
the MAPT SNPs with AD risk.
PMID- 28415652
TI - The clinical role of microRNA-21 as a promising biomarker in the diagnosis and
prognosis of colorectal cancer: a systematic review and meta-analysis.
AB - This systematic analysis aimed to investigate the value of microRNA-21 (miR-21)
in colorectal cancer for multiple purposes, including diagnosis and prognosis, as
well as its predictive power in combination biomarkers. Fifty-seven eligible
studies were included in our meta-analysis, including 25 studies for diagnostic
meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta
analysis of miR-21 alone, the overall pooled results for sensitivity,
specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85
(0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented
corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89),
respectively. For the diagnostic meta-analysis of miR-21-related combination
biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87),
and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that
miRNA combination markers in circulation exhibited high predictive power, with
sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92
(0.89-0.94). For the prognostic meta-analysis, patients with higher expression of
miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio
(HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The
combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93),
respectively. Our comprehensive systematic review revealed that circulating miR
21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a
prognostic marker for colorectal cancer. In addition, miRNA combination
biomarkers may provide a new approach for clinical application.
PMID- 28415655
TI - Selective emodin toxicity in cancer cells.
PMID- 28415656
TI - Multivariate approaches to behavioral physiology.
PMID- 28415657
TI - ROS and radiotherapy: more we care.
PMID- 28415658
TI - Diagnostic and prognostic value of blood samples for KRAS mutation identification
in lung cancer: a meta-analysis.
AB - Circulating tumor DNA (ctDNA) and tumor cells (CTC) are novel approaches for
identifying genomic alterations. Thus, we designed a meta-analysis to evaluate
the diagnostic value and prognostic significance of a KRAS proto-oncogene, GTPase
(KRAS) mutation for lung cancer patients. All included articles were from PubMed,
EMBASE, Web of Science and Cochrane Library. Twelve articles that described 1,131
patients were reviewed. True positives (TP), false positives (FP), true negatives
(TN), and false negatives (FN) were used to calculate pooled sensitivity,
specificity, the positive likelihood ratio (PLR), the negative likelihood ratio
(NLR), a diagnostic odds ratio (DOR), the area under the curve (AUC) and
corresponding 95% confidence intervals (95% CI). PLR is calculated as
sensitivity/(1-specificity) and NLR is (1- sensitivity)/specificity. DOR is a
measured of diagnostic effectiveness (PLR/NLR). A survival analysis subgroup was
also designed to evaluate prognostic significance. Pooled sensitivity,
specificity, PLR, NLR, DOR and AUC were 0.79 (95% CI, 0.63-0.89), 0.93 (95% CI,
0.89-0.96), 12.13 (92% CI, 7.11-20.67), 0.22 (95% CI, 0.12-0.41), 54.82 (95% CI,
23.11-130.09), and 0.95 (95% CI, 0.93-0.96), respectively. KRAS mutation and wild
type hazard ratios for overall survival and progression-free survival were 1.37
(95% CI, 1.08-1.66), 1.46 (95% CI, 1.15-1.77) in blood samples, and 1.16 (95% CI,
1.03-1.28), 1.28 (95% CI, 1.09-1.46) in tumor tissue.
PMID- 28415659
TI - Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive
system: a meta-analysis.
AB - Several previous studies have reported the prognostic value of hexokinase 2 (HK2)
in digestive system tumors. However, these studies were limited by the small
sample sizes and the results were inconsistent among them. Therefore, we
conducted a meta-analysis based on 15 studies with 1932 patients to assess the
relationship between HK2 overexpression and overall survival (OS) of digestive
system malignancies. The relationship of HK2 and clinicopathological features was
also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence
intervals (CI) were calculated to estimate the effect size. Positive HK2
expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P < 0.001).
When stratified by tumor type, the impact of HK2 overexpression on poor prognosis
was observed in gastric cancer (HR = 1.77 [1.25-2.50], P < 0.001), hepatocellular
carcinoma (HR = 1.87 [1.58-2.21], P < 0.001), and colorectal cancer (HR = 2.89
[1.62-5.15], P < 0.001), but not in pancreatic ductal adencarcinoma (HR = 1.11
[0.58-2.11], P = 0.763). Furthermore, high HK2 expression was significantly
associated with some phenotypes of tumor aggressiveness, such as large tumor size
(OR = 2.03 [1.10-3.74], P = 0.024), positive lymph node metastasis (OR = 2.05
[1.39-3.02], P < 0.001), advanced clinical stage (OR = 2.17 [1.21-3.89], P =
0.009) and high alpha fetoprotein level (OR = 1.47 [1.09-2.02] P = 0.013). In
summary, HK2 might act as a prognostic indicator and a potential therapeutic
target of these digestive system cancers.
PMID- 28415660
TI - Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain
tissue.
AB - Raman spectroscopy could be applied to distinguish tumor from normal tissues.
This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in
differentiating brain tumor from normal brain tissue. PubMed and Embase were
searched to identify suitable studies prior to Jan 1st, 2016. We estimated the
pooled sensitivity, specificity, positive and negative likelihood ratios (LR),
diagnostic odds ratio (DOR), and constructed summary receiver operating
characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in
differentiating brain tumor from normal brain tissue. A total of six studies with
1951 spectra were included. For glioma, the pooled sensitivity and specificity of
Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99),
respectively. The area under the curve (AUC) was 0.9831. For meningioma, the
pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI
0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that
Raman spectroscopy could be an effective and accurate tool for differentiating
glioma and meningioma from normal brain tissue, which would help us both avoid
removal of normal tissue and minimize the volume of residual tumor.
PMID- 28415661
TI - Specific amplifications and copy number decreases during human neural stem cells
differentiation towards astrocytes, neurons and oligodendrocytes.
AB - There is growing evidence that gene amplifications are an attribute of normal
cells during development and differentiation. During neural progenitor cell
differentiation half of the genome is involved in amplification process. To
answer the question how specific amplifications occur at different stages and in
different lineages of differentiation we analyzed the genes CDK4, MDM2, EGFR,
GINS2, GFAP, TP53, DDB1 and MDM4 in human neural stem cells that were induced to
differentiate towards astrocytes, neurons and oligodendrocytes. We found specific
amplification pattern for each of the eight analyzed genes both in
undifferentiated neural stem and progenitor cells and in cells that were induced
for differentiation. Different amplification patterns were also found between
adherently grown neural stem cells and cells that were grown as spheres. The most
frequently amplified genes were MDM2 and CDK4 with the latter amplified in all
three lineages at all analyzed stages. Amplification of the analyzed genes was
also found in four glioma stem-like cells. The combined amplification data of
stem cells and of tumor stem cells can help to define cell populations at the
origin of the tumor. Furthermore, we detected a decrease of gene copies at
specific differentiation stages most frequently for MDM4. This study shows
specific amplification pattern in defined stem cell populations within specific
time windows during differentiation processes indicating that amplifications
occur in an orderly sequence during the differentiation of human neural stem and
progenitor cells.
PMID- 28415663
TI - Prognostic value of progesterone receptor expression in ovarian cancer: a meta
analysis.
AB - OBJECTIVE: While a prognosis value of progesterone receptor (PR) in ovarian
cancer has been reported in some publications, controversial data were presented
by different reports. In order to address the disagreement of progesterone
receptor in ovarian cancer survival, we conducted this meta-analysis. METHODS:
Relevant articles on progesterone receptor and ovarian cancer prognosis were
identified via a thorough search of PubMed, Embase and Cochrane Central. Hazard
ratios (HR) and 95% confidence interval (CI) were extracted from studies on
overall survival (OS) and disease-free survival (DFS)/progress-free survival
(PFS)/recurrence-free survival (RFS). RESULT: A total of 28 eligible studies
containing 5685 patients were collected for analysis. It was found that
progesterone receptor positivity was significantly associated with favorable
overall survival (OS) (HR = 0.86, 95% CI = 0.78 to 0.95, P = 0.002) and disease
free survival (DFS)/progress-free survival (PFS)/recurrence-free survival (RFS)
(HR = 0.75, 95% CI = 0.61 to 0.93, P = 0.008) of ovarian cancer patients.
Subgroup analysis showed that progesterone receptor expression was associated
with a favorable prognosis of unclassified ovarian cancer, European origin, and
immunohistochemical detection method. CONCLUSION: Progesterone receptor
expression can be used as a favorable prognostic predictor in ovarian cancer
managements.
PMID- 28415664
TI - Clinical application of the supraorbital key-hole approach to the treatment of
unilateral-dominant bilateral frontal contusions.
AB - We compared the surgical efficacy of the supraorbital key-hole approach (SKA) to
conventional unilateral frontotemporal craniotomy (UFTC) for the treatment of
patients with unilateral-dominant bilateral frontal contusions (BFCs). A
retrospective analysis of 62 patients with unilateral-dominant BFCs who underwent
surgery at our institute between 2014 and 2017 was performed. There were 26
patients who underwent SKA (group A) and 36 who underwent UFTC (group B).
Postoperative computed tomography scans showed satisfactory evacuation of the
frontal cerebral contusions in both groups (p > 0.05). There was less
intraoperative blood loss in group A than group B (17.1 +/- 4.55 vs. 67.6 +/-
10.28 mL, p < 0.05). The operative time was also shorter in group A (82.7 +/-
13.73 vs. 132.4 +/- 9.17 min, p < 0.05). Postoperative bleeding occurred in three
cases in group A and in only one case in group B (p > 0.05). The average length
of hospitalization was shorter in group A than group B (7.3 +/- 1.09 vs. 12.9 +/-
1.71 days, p < 0.05). No differences in the Glasgow Outcome Scale were observed
between the two groups after 6 months of follow-up (p > 0.05). Thus, compared to
UFTC, SKA is associated with shorter operation times and less trauma to the
surrounding brain tissue.
PMID- 28415662
TI - The hypoxia signalling pathway in haematological malignancies.
AB - Haematological malignancies are tumours that affect the haematopoietic and the
lymphatic systems. Despite the huge efforts to eradicate these tumours, the
percentage of patients suffering resistance to therapies and relapse still
remains significant. The tumour environment favours drug resistance of cancer
cells, and particularly of cancer stem/initiating cells. Hypoxia promotes
aggressiveness, metastatic spread and relapse in most of the solid tumours.
Furthermore, hypoxia is associated with worse prognosis and resistance to
conventional treatments through activation of the hypoxia-inducible factors.
Haematological malignancies are not considered solid tumours, and therefore, the
role of hypoxia in these diseases was initially presumed to be inconsequential.
However, hypoxia is a hallmark of the haematopoietic niche. Here, we will review
the current understanding of the role of both hypoxia and hypoxia-inducible
factors in different haematological tumours.
PMID- 28415667
TI - Effect of radiotherapy after breast-conserving surgery in older patients with
early breast cancer and breast ductal carcinoma in situ: a meta-analysis.
AB - BACKGROUND: There are no consistent agreements on whether radiotherapy after
breast-conserving surgery (BCS) could provide local control and survival benefit
for older patients with early breast cancer or breast ductal carcinoma in situ
(DCIS). The present study aimed to evaluate the efficacy of radiotherapy after
BCS in older patients with early breast cancer or DCIS. RESULTS: Radiotherapy
could reduce the risk of local relapse in older patients with early breast
cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non
radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25.
The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non
radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20.
However, radiotherapy could not improve survival benefits, including overall
survival, cancer-specific survival, breast-cancer-specific survival, and distant
relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast
events in older patients with DCIS. MATERIALS AND METHODS: PubMed and Embase
database were searched for relevant studies. Hazard ratios (HRs), risk ratios
(RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to
treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy
in older patients. CONCLUSIONS: Our study indicates that radiotherapy could
slightly reduce the risk of local relapse in older patients with favorable early
breast cancer. However, radiotherapy cannot translate into significant survival
benefits.
PMID- 28415668
TI - MiR-let-7a inhibits cell proliferation, migration, and invasion by down
regulating PKM2 in cervical cancer.
AB - In recent decades, miRNA has been reported as a crucial modulator in some biology
progressions. This work aims to assess the expression and role of miR-let-7a and
pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we
identified that miR-let-7a expression was decreased in CC tissues, and SiHa and
HeLa cells (all P < 0.001), however, PKM2 expression was increased in these
samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or
protein (p = 0.013, p = 0.015, respectively). In-vitro assays revealed that
ectopic miR-let-7a expression repressed SiHa and HeLa cell proliferation,
migration and invasion, and enhanced SiHa and HeLa cell apoptosis. Furthermore,
luciferase reporter assays revealed the 3'-UTR of PKM2 was identified a target of
miR-let-7a, by which miR-let-7a affected the expression of PKM2 in SiHa and HeLa
cells. Besides, PKM2 plasmids partially abrogated the inhibitory effects of miR
let-7a, while si-PKM2 enhanced the inhibitory effects of miR-let-7a. In vivo, miR
let-7a mimics indeed repressed tumor growth in mice xenograft model. In
conclusion, our results demonstrated that miR-let-7a inhibits cell proliferation,
migration and invasion by down-regulation of PKM2 in cervical cancer. miR-let
7a/PKM2 pathway may be a useful therapeutic target for CC patients.
PMID- 28415669
TI - Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post
cardio transplantation.
AB - The immune tolerance to the transplant heart survival is critical. Regulatory B
cells are one of the major immune regulatory cell populations in the immune
tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as
the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis
that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10
expression in B cells (B10 cell) after heart transplantation. In this study, the
peripheral blood samples were collected from patients before and after heart
transplantation. The expression of miR-98 and IL-10 in B cells was assessed by
real time RT-PCR. An allograft heart transplantation mouse model was developed.
We observed that after heart transplantation, the frequency of peripheral B10
cell and the IL-10 mRNA levels in peripheral B cells were significantly
decreased, the levels of miR-98 were increased in peripheral B cells and the
serum levels of cortisol were increased in the patients. Treating naive B cells
with cortisol in the culture suppressed the expression of IL-10 in B cells, which
was abolished by knocking down the miR-98 gene. Administration with anti-miR-98,
or cortisol inhibitor, or adoptive transfer with B10 cells, significantly
enhanced the survival rate and time of mice received allograft heart
transplantation. In conclusion, the enhancement of serum cortisol affects the
immune tolerant feature of B cells, which can be attenuated by anti-miR-98
carrying liposomes.
PMID- 28415671
TI - Predictors and prognosticators for survival with Yttrium-90 radioembolization
therapy for unresectable colorectal cancer liver metastasis.
AB - This critical review aims to explore predictive and prognostic biomarkers of
Yttrium-90 (Y90) radioembolization therapy of colorectal liver metastases. A
brief overview of established predictive and prognostic molecular and genetic
biomarkers in colorectal cancer therapies will be discussed. A review of the
literature on imaging modalities, genetic, metabolic and other molecular markers
and the subsequent outcomes in post-Y90 treatment will be presented. How these
biomarkers and future biomarker research can inform locoregional treatment
decisions in the clinical setting of metastatic colorectal cancer lesions of the
liver will be explored. There are opportunities for personalized cancer treatment
in the setting of Y90 radioembolization. The ability to predict tumor response
after Ytrium-90 radioembolization therapy can greatly impact clinical decision
making and enhance treatment outcomes, therefore further research into the field
is needed.
PMID- 28415673
TI - cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2
induced learning/memory deficits of rats subjected to chronic unpredictable mild
stress.
AB - To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory
impairments in rats subjected to chronic unpredictable mild stress (CUMS),
meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2.
Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was
injected intraventricularly to increase or decrease the enzyme's expression,
respectively. The body weights and sucrose consumption were used to analyze
depressive behaviors, while the Morris water maze and step-down-type passive
avoidance tests were carried out to evaluate the learning-memory functions. The
levels of inflammatory cytokines were measured to estimate inflammation and the
contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels
of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed
using reverse transcription polymerase chain reaction. Moreover, the expression
of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins
receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein
(CREB), and phosphorylated CREB were estimated using immunohistochemical staining
or western blotting. The results showed that CUMS led to significant depressive
like behaviors and learning and memory dysfunctions. Also, the cAMP levels
decreased significantly, while levels of inflammatory cytokines and
prostaglandins E2 increased significantly. The expressions of PKA, BDNF,
phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam
and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS
while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities.
The findings also showed that CUMS increased cyclooxygenase 2 expression, which
can cause learning and memory impairments, mainly through activating the
hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.
PMID- 28415674
TI - Primary Sjogren's syndrome with diffuse cystic lung changes developed systemic
lupus erythematosus: a case report and literature review.
AB - Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease that can
occur as a unique existence (primary Sjogren's syndrome) or merge with other
systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis
or systemic sclerosis (secondary Sjogren's syndrome). Data on the two diseases
occurrence order are inadequate. Primary Sjogren's syndrome (pSS) may relatively
uncommonly lead to diffuse cystic lung changes. We represent a female who was
diagnosed pSS with diffuse cystic lung alterations developed SLE two years later.
SS was diagnosed on account of the existence of dryness of eye and mouth,
Schirmer's test, biopsy of the minor salivary glands of her lip, positive anti
SSA and anti-SSB antibody in the serum. Chest computed tomography image showed
bilateral diffuse cystic changes with a wide variation in cyst size and
distribution. SLE was finally diagnosed based on bilateral lower limb skin rash,
gonarthritis and omarthritis, low level of complement, antinuclear antibody 1:640
and positive antibodies to double-stranded DNA. Improvement was achieved with
therapy of corticosteroids, hydroxychloroquine and antibiotics. This report
provides us clinical, diagnosis and treatment perception of SS-onset SLE as
patient presenting diffuse cystic lung changes.
PMID- 28415675
TI - Elevated microRNA-135a is associated with pulmonary arterial hypertension in
experimental mouse model.
AB - Multiple causes are associated with the complex mechanism of pathogenesis of
pulmonary arterial hypertension (PAH), but the molecular pathway in the
pathogenesis of PAH is still insufficiently understood. In this study, we
investigated epigenetic changes that cause PAH induced by exposure to combined
Th2 antigen (Ovalbumin, OVA) and urban particulate matter (PM) in mice. To
address that, we focused on the epigenetic mechanism, linked to microRNA (miR)
135a. We found that miR-135a levels were significantly increased, and levels of
bone morphogenetic protein receptor type II (BMPR2) which is the target of miR
135a, were significantly decreased in this experimental PAH mouse model.
Therefore to evaluate the role of miR-135a, we injected AntagomiR-135a into this
mouse model. AntagomiR-135a injected mice showed decreased right ventricular
systolic pressures (RVSPs), right ventricular hypertrophy (RVH), and the
percentage of severely thickened pulmonary arteries compared to control scrambled
miRNA injected mice. Both mRNA and protein expression of BMPR2 were recovered in
the AntagomiR-135a injected mice compared to control mice. Our study understands
if miR-135a could serve as a biomarker helping to manage PAH. The blocking of miR
135a could lead to new therapeutic modalities to alleviate exacerbation of PAH
caused by exposure to Th2 antigen and urban air pollution.
PMID- 28415676
TI - Nitrobenzylthioinosine mimics adenosine to attenuate the epileptiform discharge
of hippocampal neurons from epileptic rats.
AB - Nitrobenzylthioinosine (NBTI), a specific inhibitor of type 1 equilibrative
nucleoside transporter, could regulate the extracellular adenosine concentration
and have protective roles in seizures. However, the protection mechanism of NBTI
in seizures remains poorly understood. Here, the expression pattern and
subcellular distribution of adenosine A1 receptor were detected by Western blot
analysis and double-labeling immunofluorescence staining in Lithium Chloride
Pilocarpine induced epileptic rat model. At 24 h after pilocarpine induced rat
seizures, hippocampal slices were prepared and the evoked excitatory postsynaptic
currents (eEPSCs) amplitude of pyramidal neurons in hippocampus CA1 region was
recorded using whole-cell patch clamp. In vivo, compared to control group,
Western blotting analysis showed that the expression of adenosine A1 receptor
protein was increased at 24 h and 72 h after seizure, didn't change at 0 min and
1 w, and decreased at 2 w. Double-label immunofluorescence revealed that
adenosine A1 receptor was mainly expressed in the membrane and cytoplasm of
neurons. In Vitro, adenosine decreased the eEPSCs amplitude of pyramidal neurons
in hippocampus CA1 region, NBTI also had the same effect. Meantime, NBTI could
further inhibit eEPSCs amplitude on the basis of lower concentration adenosine
(50uM), and adenosine A1 receptor inhibitor DPCPX partially reversed this effect.
Taken together, we confirmed that the expression of adenosine A1 receptor protein
was increased in the early seizures and decreased in the late seizures. At the
same time, NBTI mimics adenosine to attenuate the epileptiform discharge through
adenosine A1 receptor, which might provide a novel therapeutic approach toward
the control of epilepsy.
PMID- 28415677
TI - Selective elimination of long INterspersed element-1 expressing tumour cells by
targeted expression of the HSV-TK suicide gene.
AB - In gene therapy, effective and selective suicide gene expression is crucial. We
exploited the endogenous Long INterspersed Element-1 (L1) machinery often
reactivated in human cancers to integrate the Herpes Simplex Virus Thymidine
Kinase (HSV-TK) suicide gene selectively into the genome of cancer cells. We
developed a plasmid-based system directing HSV-TK expression only when reverse
transcribed and integrated in the host genome via the endogenous L1 ORF1/2
proteins and an Alu element. Delivery of these new constructs into cells followed
by Ganciclovir (GCV) treatment selectively induced mortality of L1 ORF1/2 protein
expressing cancer cells, but had no effect on primary cells that do not express
L1 ORF1/2. This novel strategy for selective targeting of tumour cells provides
high tolerability as the HSV-TK gene cannot be expressed without reverse
transcription and integration, and high selectivity as these processes take place
only in cancer cells expressing high levels of functional L1 ORF1/2.
PMID- 28415679
TI - A feasibility study of returning clinically actionable somatic genomic
alterations identified in a research laboratory.
AB - PURPOSE: Molecular profiling performed in the research setting usually does not
benefit the patients that donate their tissues. Through a prospective protocol,
we sought to determine the feasibility and utility of performing broad genomic
testing in the research laboratory for discovery, and the utility of giving
treating physicians access to research data, with the option of validating
actionable alterations in the CLIA environment. EXPERIMENTAL DESIGN: 1200
patients with advanced cancer underwent characterization of their tumors with
high depth hybrid capture sequencing of 201 genes in the research setting. Tumors
were also tested in the CLIA laboratory, with a standardized hotspot mutation
analysis on an 11, 46 or 50 gene platform. RESULTS: 527 patients (44%) had at
least one likely somatic mutation detected in an actionable gene using hotspot
testing. With the 201 gene panel, 945 patients (79%) had at least one alteration
in a potentially actionable gene that was undetected with the more limited CLIA
panel testing. Sixty-four genomic alterations identified on the research panel
were subsequently tested using an orthogonal CLIA assay. Of 16 mutations tested
in the CLIA environment, 12 (75%) were confirmed. Twenty-five (52%) of 48 copy
number alterations were confirmed. Nine (26.5%) of 34 patients with confirmed
results received genotype-matched therapy. Seven of these patients were enrolled
onto genotype-matched targeted therapy trials. CONCLUSION: Expanded cancer gene
sequencing identifies more actionable genomic alterations. The option of CLIA
validating research results can provide alternative targets for personalized
cancer therapy.
PMID- 28415680
TI - Long-term neurocognitive dysfunction in offspring via NGF/ ERK/CREB signaling
pathway caused by ketamine exposure during the second trimester of pregnancy in
rats.
AB - Early life exposure to ketamine caused neurohistopathologic changes and
persistent cognitive dysfunction. For this study, a pregnant rat model was
developed to investigate neurocognitive effects in the offspring, following
ketamine exposure during the second trimester. Pregnant rats on gestational day
14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg
ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition
test, and fear conditioning) at postnatal days (P25-30). Furthermore, hippocampal
morphology of the offspring (P30) was examined via Nissl staining and hippocampal
dendritic spine density was determined via Golgi staining. The hippocampal
protein levels of nerve growth factor (NGF), extracellular signal-regulated
kinase (ERK), phosphorylated-ERK (p-ERK), cyclic adenosine monophosphate response
element-binding (CREB), p-CREB, synaptophysin (SYP), synapsin (SYN), and
postsynaptic density-95 (PSD95) were measured via western blot. Additionally,
SCH772984 (an ERK inhibitor) was used to evaluate both role and underlying
mechanism of the ERK pathway in PC12 cells. We found that ketamine caused long
term neurocognitive dysfunction, reduced the density of the dendritic spin,
caused neuronal loss, and down-regulated the expression of NGF, ERK, p-ERK,
mitogen, and stress-activated protein kinase (MSK), CREB, p-CREB, SYP, SYN, and
PSD95 in the hippocampus. These results suggest that ketamine induced maternal
anesthesia during period of the fetal brain development can cause long-term
neurocognitive dysfunction in the offspring, which likely happens via inhibition
of the NGF-ERK-CREB pathway in the hippocampus. Our results highlight the central
role of ERK in neurocognition.
PMID- 28415681
TI - A reproducible model of intramedullary spinal cord tumor in rats bearing RG2
cells.
AB - Intramedullary spinal cord tumors (IMSCTs) are lethal diseases to many patients.
The lack of adequate animal model has hampered the development of novel
treatments. In the current study, a rodent intramedullary glioma model is
established to study IMSCT progression. Fischer 344 rats received a
intramedullary implantation of RG2 glioma cells. The neurological state of each
rat was evaluated on daily basis using the Basso, Beattie and Bresnahan (BBB)
scale. Rats implanted with RG2 cells developed significant hind limb paraplegia
20 days after implantation. Magnetic resonance imaging (MRI) scans after three
weeks revealed significant intramedullary RG2 tumors in the rats. Forty days post
implantation, rats were sacrificed for histopathological examination. Neuro
imaging and HE staining cross sections confirmed intramedullary RG2 glioma cells
invading to the spinal cord. Thus, our model displayed many of the same invasive
characteristics as human IMSCTs. This model should be a reliable and reproducible
methodology to correlate well with the features of human IMSCT.
PMID- 28415682
TI - Low dose of 2-deoxy-D-glucose kills acute lymphoblastic leukemia cells and
reverses glucocorticoid resistance via N-linked glycosylation inhibition under
normoxia.
AB - Recent studies showed that 2-deoxy-D-glucose (2-DG), a glucose analog with dual
activity of inhibiting glycolysis and N-linked glycosylation, can be selectively
taken up by cancer cells and be used as a potential chemo- and radio-sensitizer.
Meanwhile, 2-DG can kill cancer cells under normoxia. However, its efficacy is
limited by the high-dose induced systemic toxicity. Here, we showed that low-dose
2-DG could be used as a single agent to kill acute lymphoblastic leukemia (ALL)
cells, and as a GC sensitizer to overcome GC resistance under normoxia. Addition
of exogenous mannose, a sugar essential for N-linked glycosylation, rescued 2-DG
treated ALL cells, indicating that inhibition of N-linked glycosylation and
induction of endoplasmic reticulum stress is the main mechanism for 2-DG to
induce cell death and reverse GC resistance in ALL cells. These data provides new
insight into the molecular mechanisms involved in GC resistance. More important,
it indicates that 2-DG might be the promising drug for designing novel high
efficiency and low toxic protocol for ALL patients.
PMID- 28415683
TI - Suppression of PKC causes oncogenic stress for triggering apoptosis in cancer
cells.
AB - Gain of functional mutations in ras occurs in more than 30% of human malignancies
and in particular 90% of pancreatic cancer. Mutant ras, via activating multiple
effector pathways, not only promote cell growth or survival, but also apoptosis,
depending upon cell types or circumstances. In order to further study the
mechanisms of apoptosis induced by oncogenic ras, we employed the ras loop mutant
genes and demonstrated that Akt functioned downstream of Ras in human pancreatic
cancer or HPNE cells ectopically expressing mutated K-ras for the induction of
apoptosis after the concurrent suppression of PKC alpha and beta. In this
apoptotic process, the redox machinery was aberrantly switched on in the
pancreatic cancer cells as well as prostate cancer DU145 cells. p73 was
phosphorylated and translocated to the nucleus, accompanied with UPR activation
and induction of apoptosis. The in vitro results were corroborated by the in vivo
data. Thus, our study indicated that PKC alpha and beta appeared coping with
oncogenic Ras or mutated Akt to maintain the balance of the homeostasis in cancer
cells. Once these PKC isoforms were suppressed, the redox state in the cancer
cells was disrupted, which elicited persistent oncogenic stress and subsequent
apoptotic crisis.
PMID- 28415684
TI - The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma
driver genes by microRNA sponge activity.
AB - Long noncoding RNAs (lncRNAs) are major regulators of physiological and disease
related gene expression, particularly in the central nervous system. Dysregulated
lncRNA expression has been documented in several human cancers, and their tissue
specificity makes them attractive candidates as diagnostic/prognostic biomarkers
and/or therapeutic agents. Here we show that linc-NeD125, which we previously
characterized as a neuronal-induced lncRNA, is significantly overexpressed in
Group 4 medulloblastomas (G4 MBs), the largest and least well characterized
molecular MB subgroup. Mechanistically, linc-NeD125 is able to recruit the miRNA
induced silencing complex (miRISC) and to directly bind the microRNAs miR-19a-3p,
miR-19b-3p and miR-106a-5p. Functionally, linc-NeD125 acts as a competing
endogenous RNA (ceRNA) that, sequestering the three miRNAs, leads to de
repression of their targets CDK6, MYCN, SNCAIP, and KDM6A, which are major driver
genes of G4 MB. Accordingly, linc-NeD125 downregulation reduces G4 cell
proliferation. Moreover, we also provide evidence that linc-NeD125 ectopic
expression in the aggressive Group 3 MB cells attenuates their proliferation,
migration and invasion.This study unveils the first lncRNA-based ceRNA network in
central nervous system tumours and provides a novel molecular circuit underlying
the enigmatic Group 4 medulloblastoma.
PMID- 28415685
TI - Identification of molecular targets for esophageal carcinoma diagnosis using
miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases.
AB - Esophageal carcinoma (ESCA) is one of the most common malignancies worldwide, and
its pathogenesis is complex. In this study, we identified differentially
expressed miRNAs (DEMs) and genes (DEGs) of ESCA from The Cancer Genome Atlas
(TCGA) database. The diagnostic values of DEMs were determined by receiver
operating characteristic (ROC) analyses and validated based on data from Gene
Expression Omnibus (GEO). The top five DEMs with the best diagnostic values were
selected, and their potential targets were predicted by various in silico
methods. These target genes were then identified among the DEGs from TCGA.
Furthermore, the overlapping genes were subjected to protein-protein interaction
(PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
(KEGG) pathway analyses. The miRNA-transcription factor (TF) regulatory relations
were determined using CircuitsDB and TransmiR. Finally, the regulatory networks
of miRNA-TF and miRNA-gene were constructed and analyzed. A total of 136 DEMs and
3541 DEGs were identified in ESCA. The top five DEMs with the highest area under
the receiver operating characteristic curve (AUC) values were miRNA-93 (0.953),
miRNA-21 (0.928), miRNA-4746 (0.915), miRNA-196a-1 (0.906) and miRNA-196a-2
(0.906). The combined AUC of these five DEMs was 0.985. The KEGG analysis with
349 overlapping genes showed that the calcium signaling pathway and the
neuroactive ligand-receptor interaction were the most relevant pathways. The
regulatory networks of miRNA-TF and miRNA-gene, including 38 miRNA-TF and 560
miRNA-gene pairs, were successfully established. Our findings may provide new
insights into the molecular mechanisms of ESCA pathogenesis. Future research will
aim to explore the role of novel miRNAs in the pathogenesis and improve the early
diagnosis of ESCA.
PMID- 28415686
TI - Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose
tissue of mice through inhibition of NLRP3 inflammasome activation and NF-kappaB
signaling.
AB - Chronic metabolic inflammation in adipose tissue plays an important role in the
development of obesity-associated diseases. Our previous study indicated that
total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one
main component of SPJ, could exert the anti-oxidative and anti-inflammatory
effects. The present study aimed to investigate the in vivo and Ex vivo anti
inflammatory activities of another main component of SPJ, namely Chikusetsu
saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis,
and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA
expression levels of inflammation-related genes and secretion of the
chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages
(ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced
expression of NLRP3 inflammasome component genes and decreased IL-1beta and
Caspase-1 production in mice. Moreover, CS treatment also inhibited the
activation of NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs).
Meanwhile, CS treatment inhibited an NLRP3-induced ASC pyroptosome formation and
lipopolysaccharide (LPS)-induced pyroptosis. Furthermore, CS treatment suppressed
HFD-induced NF-kappaB signaling in vivo and LPS-induced NF-kappaB activation as
reflected by the fact that their phosphorylated forms and the ratios of pNF
kappaB/NF-kappaB, pIKK/IKK, and pIkappaB/IkappaB were all decreased in EAT from
HFD-fed mice treated with CS as compared with those of HFD mice. Taking together,
this study has revealed that CS effectively inhibits HFD-induced inflammation in
adipose tissue of mice through inhibiting both NLRP3 inflammasome activation and
NF-kappaB signaling. Thus, CS can serve as a potential therapeutic drug in the
prevention and treatment of inflammation-associated diseases.
PMID- 28415687
TI - The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small
cell lung cancer patients treated with definitive concurrent chemo-radiotherapy.
AB - BACKGROUND: This study aimed to investigate the prognostic impact of
supraclavicular lymph node (SCN) metastasis in patients who were treated with
definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer
(NSCLC). RESULTS: The 2- and 5-year overall survival (OS) rates were 57.3% and
35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN
metastasis, respectively. The median OS was 34 months in both groups. There was
no significant difference in OS between the two groups (p = 0.679). The 2- and 5
year progression-free survival (PFS) rates were 24.1% and 12.6% in patients
without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis,
respectively. Patients without SCN metastasis had slightly longer median PFS (10
months vs. 8 months), but the difference was not statistically significant (p =
0.223). In multivariate analysis, SCN metastasis was not a significant factor for
OS (p = 0.391) and PFS (p = 0.149). MATERIALS AND METHODS: This retrospective
analysis included 204 consecutive patients who were treated with
chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A
median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients
(58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease:
mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one
(1.2%). The patients were divided into two groups according to SCN metastasis.
CONCLUSIONS: SCN metastasis does not compromise treatment outcomes compared to
other mediastinal metastasis in the setting of definitive chemoradiotherapy.
PMID- 28415688
TI - Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3
M cells by competitively binding to oncogenic FABP5.
AB - Castration resistant-prostate cancer is largely impervious to feather hormonal
therapy and hence the outlook for patients is grim. Here we use an approach to
attach the recently discovered Achilles heel. The experimental treatment
established in this study is based on the recent discovery that it is the FABP5
PPARgamma-VEGF signalling axis, rather than the androgen receptor pathway, played
a dominant role in promoting the malignant progression of castration resistant
prostate cancer cells. Treatments have been established in mice by suppressing
the biological activity of FABP5 using a chemical inhibitor SBFI26. The inhibitor
significantly suppressed the proliferation, migration, invasiveness and colony
formation of PC3-M cells in vitro. It also produced a highly significant
suppression of both the metastases and the primary tumours developed from cancer
cells implanted orthotopically into the prostate glands of the mice. The
inhibitor SBFI26 interferes with the FABP5-PPARgamma- signalling pathway at the
initial stage of the signal transduction by binding competitively to FABP5 to
inhibit cellular fatty acid uptake. This avoids the fatty-acid stimulation of
PPARgamma and prevents it activating the down-stream regulated cancer-promoting
genes. This entirely novel experimental approach to treating castration-
resistant prostate cancer is completely different from current treatments that
are based on androgen-blockade therapy.
PMID- 28415689
TI - Targeting CD157 in AML using a novel, Fc-engineered antibody construct.
AB - Antibody-based immunotherapy represents a promising strategy to eliminate
chemorefractory leukemic cells in acute myeloid leukemia (AML). In this study, we
evaluated a novel Fc-engineered antibody against CD157 (MEN1112) for its
suitability as immunotherapy in AML. CD157 was expressed in 97% of primary AML
patient samples. A significant, albeit lower expression level of CD157 was
observed within the compartment of leukemia-initiating cells, which are supposed
to be the major source of relapse. In healthy donor bone marrow, CD157 was
expressed on CD34+ cells. In ex vivo assays, MEN1112 triggered natural killer
(NK) cell-mediated cytotoxicity against AML cell lines and primary AML cells.
Compared to its parental analogue, the Fc-engineered antibody exhibited higher
antibody dependent cellular cytotoxicity responses. Using NK cells from AML
patients, we observed heterogeneous MEN1112-mediated cytotoxicity against AML
cells, most likely due to well-documented defects in AML-NK cells and
corresponding inter-patient variations in NK cell function. Cytotoxicity could
not be correlated to the time after completion of chemotherapy. In summary, we
could demonstrate that CD157 is strongly expressed in AML. MEN1112 is a promising
antibody construct that showed high cytotoxicity against AML cells and warrants
further clinical testing. Due to variability in NK-cell function of AML patients,
the time of application during the course of the disease as well as combinatorial
strategies might influence treatment results.
PMID- 28415690
TI - Identification of DNA-PKcs as a primary resistance factor of TIC10 in
hepatocellular carcinoma cells.
AB - The current study tested the anti-hepatocellular carcinoma (HCC) cell activity of
TIC10, a first-in-class small-molecule tumor necrosis (TNF)-related apoptosis
inducing ligand (TRAIL) inducer. TIC10 exerted potent anti-proliferative and pro
apoptotic actions in primary and established human HCC cells. TIC10 blocked Akt
Erk activation, leading to Foxo3a nuclear translocation, as well as TRAIL and
death receptor-5 (DR5) transcription in HCC cells. We propose that DNA-PKcs is a
major resistance factor of TIC10 possibly via inhibiting Foxo3a nuclear
translocation. DNA-PKcs inhibition, knockdown or mutation facilitated TIC10
induced Foxo3a nuclear translocation, TRAIL/DR5 expression and cell apoptosis.
Reversely, exogenous DNA-PKcs over-expression inhibited above actions by TIC10.
In vivo, oral administration of TIC10 significantly inhibited HepG2 tumor growth
in nude mice, which was further potentiated with Nu7026 co-administration. Thus,
TIC10 shows promising anti-HCC activity, alone or together with DNA-PKcs
inhibitors.
PMID- 28415691
TI - A potentially functional variant of ARID1B interacts with physical activity in
association with risk of hepatocellular carcinoma.
AB - The tumor suppressor role of AT-rich interactive domain containing protein 1B
(ARID1B) has drawn much attention in area of cancer etiology. However, it had
remained unknown whether or not genetic variants of ARID1B involved in
development of hepatocellular carcinoma (HCC). In this study, three putatively
functional variants in ARID1B (rs73013281C>T, rs167007A>G, and rs9397984C>T) were
selected using bioinformatics tools, and a case-control study of 611 cases and
614 controls was conducted to investigate genetic associations with HCC risk in a
Southern Chinese population. Two-dimensional gene-environment interactions were
also explored using both multiplicative and additive scales. A dominant effect of
the rs73013281 was found for HCC risk, with an adjusted odds ratio (OR) of 1.70
[95% confidence interval (CI) = 1.03-2.80] for the CT/TT genotypes compared to
the CC genotype. In stratified analysis, the detrimental effect of the T allele
on elevated HCC risk was attenuated by physical activity, with an adjusted OR of
2.75 (95% CI = 1.39-5.41) among inactive individuals against that of 0.89 (95% CI
= 0.42-1.91) in those who exercised regularly. Expectably, the rs73013281 showed
both multiplicative and additive interactions with physical activity (P = 0.037
and 0.006, respectively). In conclusion, these results highlighted the
significant genetic contribution of the ARID1B variant, rs73013281, to
susceptibility for HCC, especially in interaction with physical activity.
PMID- 28415692
TI - Novel Akt activator SC-79 is a potential treatment for alcohol-induced
osteonecrosis of the femoral head.
AB - Alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH). We
explored the molecular mechanisms underlying alcohol-induced ONFH and
investigated the protective effect of the novel Akt activator SC-79 against this
disease. We found that ethanol inhibited expression of the osteogenic genes RUNX2
and OCN, downregulated osteogenic differentiation, impaired the recruitment of
Akt to the plasma membrane, and suppressed Akt phosphorylation at Ser473, thereby
inhibiting the Akt/GSK3beta/beta-catenin signaling pathway in bone mesenchymal
stem cells. To assess SC-79's ability to counteract the inhibitory effect of
ethanol on Akt-Ser73 phosphorylation, we performed micro-computerized tomography
and immunofluorescent staining of osteopontin, osteocalcin and collagen type 1 in
a rat model of alcohol-induced ONFH. We found that SC-79 injections inhibited
alcohol-induced osteonecrosis. These results show that alcohol-induced ONFH is
associated with suppression of p-Akt-Ser473 in the Akt/GSK3beta/beta-catenin
signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment
to rescue Akt activation could be tested in the clinic as a potential therapeutic
approach to preventing the development of alcohol-induced ONFH.
PMID- 28415693
TI - CCR4 is a determinant of melanoma brain metastasis.
AB - We previously identified the chemokine receptor CCR4 as part of the molecular
signature of melanoma brain metastasis. The aim of this study was to determine
the functional significance of CCR4 in melanoma brain metastasis. We show that
CCR4 is more highly expressed by brain metastasizing melanoma cells than by local
cutaneous cells from the same melanoma. Moreover, we found that the expression of
CCR4 is significantly higher in paired clinical specimens of melanoma metastases
than in samples of primary tumors from the same patients. Notably, the expression
of the CCR4 ligands, Ccl22 and Ccl17 is upregulated at the earliest stages of
brain metastasis, and precedes the infiltration of melanoma cells to the brain.
In-vitro, CCL17 induced migration and transendothelial migration of melanoma
cells. Functionally, human melanoma cells over-expressing CCR4 were more
tumorigenic and produced a higher load of spontaneous brain micrometastasis than
control cells. Blocking CCR4 with a small molecule CCR4 antagonist in-vivo,
reduced the tumorigenicity and micrometastasis formation of melanoma cells. Taken
together, these findings implicate CCR4 as a driver of melanoma brain metastasis.
PMID- 28415694
TI - Single nucleotide polymorphisms in CIDEC gene are associated with metabolic
syndrome components risks and antihypertensive drug efficacy.
AB - The association of single nucleotide polymorphisms rs1053239 and rs2479 of cell
death-inducing DFFA-like effector c with the risk of metabolic syndrome and its
components, and with the efficacy and cost-effectiveness of antihypertensive
drugs was investigated. Totally 1064 subjects with metabolic syndrome and 1099
controls of Chinese Han nationality were recruited. Clinical assessment was
conducted with medication records collected at baseline and during 5-year follow
up. Carriers of rs2479 A allele were at higher risk to develop elevated fasting
glucose than non-carriers (P = 0.004). A allele at rs2479 were associated with a
5-year aggravation of blood triglyceride (P < 0.001) and diastolic blood pressure
(P = 0.003), and C allele at rs1053239 with the exacerbation of systolic (P <
0.001) and diastolic blood pressure (P = 0.001). Moreover, efficacy and cost
effectiveness of angiotensin II-targeted drugs were higher in subjects with
rs2479 A allele or rs1053239 C allele. These findings suggest that carriers of
rs2479 A allele are predisposed to the development of increased fasting glucose,
and the progressive elevation of blood triglyceride. Individuals with A allele at
rs2479 or C allele at rs1053239 are more susceptible to a rapid progression of
blood pressure, and benefit more from angiotensin II-targeted therapy.
PMID- 28415695
TI - Detection of COPB2 as a KRAS synthetic lethal partner through integration of
functional genomics screens.
AB - Mutated KRAS plays an important role in many cancers. Although targeting KRAS
directly is difficult, indirect inactivation via synthetic lethal partners (SLPs)
is promising. Yet to date, there are no SLPs from high-throughput RNAi screening,
which are supported by multiple screens. Here, we address this problem by
aggregating and ranking data over three independent high-throughput screens. We
integrate rankings by minimizing the displacement and by considering established
methods such as RIGER and RSA.Our meta analysis reveals COPB2 as a potential SLP
of KRAS with good support from all three screens. COPB2 is a coatomer subunit and
its knock down has already been linked to disabled autophagy and reduced tumor
growth. We confirm COPB2 as SLP in knock down experiments on pancreas and
colorectal cancer cell lines.Overall, consistent integration of high throughput
data can generate candidate synthetic lethal partners, which individual screens
do not uncover. Concretely, we reveal and confirm that COPB2 is a synthetic
lethal partner of KRAS and hence a promising cancer target. Ligands inhibiting
COPB2 may, therefore, be promising new cancer drugs.
PMID- 28415696
TI - Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta
analysis.
AB - Many molecular epidemiologic studies have explored the possible links between
interleukin-12 (IL-12) polymorphisms and various cancers. However, results from
these studies remain inconsistent. This meta-analysis is aimed to shed light on
the associations between three common loci (rs568408, rs2243115, rs3212227) of IL
12 gene and overall cancer risk. Our meta-analysis finally included 33 studies
comprising 10,587 cancer cases and 12,040 cancer-free controls. Odds ratios (ORs)
and 95% confidence intervals (CIs) were used to assess the cancer risk. We
observed a significant association between IL-12B rs3212227 and overall cancer
risk, especially in hepatocellular carcinoma, nasopharyngeal cancer, and among
Asians. IL-12A polymorphisms (rs2243115 and rs568408) were found no influence on
overall cancer risk. Nevertheless, stratification analyses demonstrated that
rs568408 polymorphism contributed to increasing cancer risk of Caucasians and
cervical cancer. And, rs2243115 may enhance the risk of brain tumor. These
findings provided evidence that IL-12 polymorphisms may play a potential role in
cancer risk.
PMID- 28415697
TI - Down-regulation of interleukin 7 receptor (IL-7R) contributes to central nervous
system demyelination.
AB - Interleukin 7 receptor (IL-7R) has been associated with the pathogenesis of
multiple sclerosis (MS), though the mechanisms are not clear. Because myelin
expression is highly conserved between zebrafish and mammals, zebrafish have
become an ideal model for studying demyelination. We used a transgenic (Tg;
mbp:nfsB-egfp) zebrafish line in which oligodendrocytes expressed green
fluorescent protein (GFP) from the larval stage to adulthood. Exposing adult
transgenic zebrafish to metronidazole induced demyelination that resembled the
morphological changes associated with the early stages of MS. The metronidazole
induced demyelination was confirmed by magnetic resonance imaging (MRI) for the
first time. Microarray analysis revealed down-regulation of IL-7R during
demyelination. Targeted knockdown of IL-7R demonstrated that IL-7R is essential
for myelination in embryonic and larval zebrafish. Moreover, IL-7R down
regulation induced signaling via the JAK/STAT pathway leading to apoptosis in
oligodendrocytes. These findings contribute to our understanding of the role of
IL-7R in demyelination, and provide a rationale for the development of IL-7R
based therapies for MS and other demyelinating diseases.
PMID- 28415698
TI - Salivary glycopatterns as potential biomarkers for diagnosis of gastric cancer.
AB - Gastric cancer (GC) is still an extremely severe health issue with high mortality
due to the lacking of effective biomarkers. In this study, we aimed to
investigate the alterations of salivary protein glycosylation related to GC and
assess the possibility of salivary glycopatterns as potential biomarkers for the
diagnosis of GC. Firstly, 94 patients with GC (n = 64) and atrophic gastritis
(AG) (n = 30), as well as 30 age- and sex-matched healthy volunteers (HV) were
enrolled in the test group to probe the difference of salivary glycopatterns
using lectin microarrays, the results were validated by saliva microarrays and
lectin blotting analysis. Then, the diagnostic model of GC (Model GC) and AG
(Model AG) were constructed based on 15 candidate lectins which exhibited
significant alterations of salivary glycopattern by logistic stepwise regression.
Finally, two diagnostic models were assessed in the validation group including HV
(n = 30) and patients with GC (n = 23) and AG (n = 24) and achieved high
diagnostic power (Model GC (AUC: 0.89, sensitivity: 0.96 and specificity: 0.80),
Model AG (AUC: 0.83, sensitivity: 0.92 and specificity: 0.72)). This study
provides pivotal information to distinguish HV, AG and GC based on precise
alterations in salivary glycopatterns, which have great potential to be
biomarkers for diagnosis of GC.
PMID- 28415699
TI - The prognostic value of histological subtype in patients with metastatic bladder
cancer.
AB - We aim to evaluate the prognostic effect of the histological sub-type in patients
with metastatic bladder cancer based on the Surveillance Epidemiology and End
Results database. A total of 2634 eligible patients were included. The
histological subtypes were: transitional cell carcinoma (TCC; 75.2%);
adenocarcinoma (3.3%); squamous cell carcinoma (SQCC; 4.1%); and small cell
carcinoma (4.3%). A significant association of adenocarcinoma with better
survival outcomes (P < 0.015), and that of SQCC with worse outcomes (P < 0.001)
was observed. On multivariate analysis, adenocarcinoma was significantly
associated with longer and SQCC with shorter survival time as compared to TCC.
Overall, 1331 (50.5%) patients had a single metastatic site and 523 (19.9%) had
multiple sites involved. Single-site metastasis had a better survival outcome
than multiple metastases (P < 0.001). Histological sub-type and presence of
multiple metastatic sites are independent predictors of survival time.
Prospective, in-depth research is needed to determine optimal therapeutic
strategies for different histological subtypes of bladder cancer with different
metastatic patterns.
PMID- 28415700
TI - Circulating tumor cells promote the metastatic colonization of disseminated
carcinoma cells by inducing systemic inflammation.
AB - Circulating tumor cells (CTCs) have been studied well in the prognosis for
malignant diseases as liquid biopsy, but their contribution to tumor metastasis
is not clearly defined. Here we report that CTCs could promote the metastatic
colonization of disseminated carcinoma cells by inducing systemic inflammation
and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in
vivo could effectively abrogate the promoting effect of CTCs on tumor cell
metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was
augmented, whereas the antitumor function of neutrophils was suppressed.
Mechanically, CTC-derived ligands for TLR2 and TLR4 (TLR2/4) induced the systemic
inflammation, thus increasing the production of proinflammatory cytokines such as
G-CSF and IL-6 that could induce the conversion of neutrophil function from tumor
suppressing to tumor-promoting. Moreover, CTCs induced the production of
endogenous TLR2/4 ligands such as S100A8, S100A9, and SAA3, which may amplify the
stimulating effect that induces the expression of proinflammatory cytokines. The
promoting effect of CTCs on tumor cell metastasis could be abrogated by
suppressing inflammatory response with IL-37, an anti-inflammatory cytokine, or
blocking CTC-derived ligands for TLR2/4. Identification of the metastatic axis of
CTCs/systemic inflammation/neutrophils may provide potential targets for
preventing tumor cell metastasis.
PMID- 28415701
TI - Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by
inhibiting Notch-1 signaling.
AB - Age-related macular degeneration and retinitis pigmentosa are major causes of
irreversible vision loss in the elderly and, despite sustained efforts, current
treatments are largely ineffective. Wogonin is a bioactive plant flavonoid
possessing a range of beneficial properties, including neuroprotective effects.
We investigated the ability of wogonin to promote retinal neuron-like
differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of
Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or
exposed to neurotrophic factors in the presence or absence of wogonin, and
western blotting, RT-PCR and immunofluorescence were used to identify changes in
molecular markers of stemness and neuroretinal differentiation. Proteins in the
Notch-1 signaling pathway, a main negative regulator of neurogenesis, were also
examined by western blotting. We found that expression of stem cell markers was
reduced, while markers of mature retinal neurons, bipolar cells and
photoreceptors were increased in wogonin-treated BMSCs. Wogonin also dose
dependently decreased expression of Notch-1 signaling proteins. Moreover,
blockade of Notch-1 both mimicked and enhanced the effect of wogonin to
facilitate BMSC differentiation into retinal neuron-like cells. Wogonin thus
appears to promote retinal neuron-like differentiation of BMSCs by antagonizing
the inhibitory actions of Notch-1 signaling on neurogenesis and may be useful in
the treatment of retinal degenerative diseases.
PMID- 28415702
TI - Overexpression of CXCR2 predicts poor prognosis in patients with colorectal
cancer.
AB - Colorectal cancer is a heterogeneous disease. Although many risk factors are used
to predict colorectal cancer patients' prognosis after surgical resection, new
prognostic factors are still needed to be defined to promote predictive efficacy
of prognosis and further guide therapies. Herein, we identified the prognostic
significance of CXCR2 in colorectal cancer patients. We retrospectively analysed
134 patients with colorectal cancer who underwent minimally invasive surgery
between 2010 and 2011. The overall cohort was divided into a training set (n =
78) and a validation set (n = 56). We detected CXCR2 expression using
immunohistochemical staining and defined the cut-off value using X-tile program.
Next, we analysed the association between CXCR2 expression and clinicopathologic
features in training and validation sets. High expression of CXCR2 was associated
with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P
= 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level
was an independent prognostic risk factor for both overall survival and disease
free survival. Kaplan-Meier survival analysis demonstrated that patients with
high expression of CXCR2 had a poor overall survival and disease free survival
even in low-risk group (I + II). This indicated that CXCR2 can help to refine
individual risk stratification. In addition, we established Nomograms of all
significant factors to predict 3- or 5-years overall survival and disease free
survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had
more significant value in predicting the prognosis than single CXCR2 factor.
PMID- 28415703
TI - Bromodomain protein 4 is a novel predictor of survival for gastric carcinoma.
AB - Expression of bromodomain protein 4 (BRD4) has been reported to predict a worse
prognosis in solid tumors. However, its expression profile and prognostic value
in gastric carcinoma (GC) remains unknown. Here we investigated BRD4 expression
in GC and explored its association with patient survival. Tissue samples were
obtained from 95 GC patients who underwent surgical resection to remove the
primary tumor from January 2009 to December 2010. Immunohistochemistry was used
to detect the expression of BRD4 in GC tissues and adjacent normal tissues.
Kaplan-Meier survival curves and Cox proportional hazards regression were used to
analyze the data of BRD4 expression profile and clinicopathological
characteristics. Immunohistochemical analysis revealed BRD4 was overexpressed in
GC tissue compared with adjacent normal tissue. BRD4 expression was significantly
associated with TNM stage (p < 0.001), lymphatic permeation (p = 0.011), and
vital status at the end of follow-up (p < 0.001). Kaplan-Meier survival curves
and the log-rank test demonstrated that higher BRD4 expression was an adverse
predictive factor for survival in GC. Multivariate analysis by Cox proportional
hazards regression revealed that BRD4 expression was an independent worse
prognostic factor in GC. In conclusion, BRD4 could act as a potential biomarker
for prognostic assessment of GC.
PMID- 28415704
TI - Maternal exposure to di-n-butyl phthalate (DBP) induces renal fibrosis in adult
rat offspring.
AB - This study was to determine the impact of maternal exposure to di-n-butyl
phthalate (DBP) on renal development and fibrosis in adult offspring. Pregnant
rats received DBP at a dose of 850 mg/kg BW/day by oral perfusion during
gestational days 14-18. In DBP exposed newborn offspring, gross observation and
histopathological examination revealed the dysplasia of kidney. The expression of
genes related to renal development was also changed. In DBP exposed adult
offspring, histopathological examination and Masson's trichrome staining revealed
the pathological changes of renal fibrosis. Furthermore, higher expression levels
of transforming growth factor- beta (TGF-beta) and alpha-smooth muscle actin
(alpha-SMA) were also detected. In vitro studies reveal that DBP promoted the
activation of NRK49F cells and G2/M arrest in NRK52E cells at a sublethal dose.
The effect of DBP on these cell lines was linked to the generation of oxidative
stress. In addition, DBP induced oxidative stress in both renal fibroblasts and
tubular epithelial cells, whereas vitamin C ameliorated the changes caused by
DBP. In conclusion, our results showed that prenatal exposure to DBP may generate
oxidative stress in both renal fibroblasts and tubular epithelial cells, leading
to kidney dysplasia and renal fibrosis.
PMID- 28415705
TI - Meta-analysis of XRCC1 polymorphism and risk of female reproductive system
cancer.
AB - Numerous epidemiological studies have evaluated the association between
polymorphism in the gene encoding x-ray repair cross complementing 1 (XRCC1)
protein and the risk of female reproductive system cancer, but results are
inconclusive. To gain a comprehensive picture of available evidence, we searched
for relevant studies in the PubMed, EMBASE, Scopus, and Chinese National
Knowledge Infrastructure databases up to December 17, 2016. A total of 26 case
control studies were picked out. The pooled odds ratio (OR) with its 95%
confidence interval (CI) was calculated to estimate the association. Based on
data of all study participants, we did not find a positive association of rs25487
or rs1799782 polymorphism with risk of female reproductive cancer risk. Subgroup
analysis, however, identified two alleles as being associated with an increased
risk of female reproductive system cancer in Asians: the A allele of rs25487
(heterozygous genetic model, OR 1.16, 95%CI 1.00-1.36), and the T allele of
rs1799782 (homozygous model, OR 2.30, 95%CI 1.39-3.82; dominant model, OR 1.28,
95%CI 1.10-1.50; recessive model, OR 2.11, 95%CI 1.33-3.34). Moreover, the AA
genotype at rs25489 was determined to be a risk factor for cervical cancer
etiology (homozygous model, OR 2.91, 95%CI, 1.17-7.26; recessive model, OR 3.16,
95%CI 1.91-5.24). This meta-analysis suggests that no association between rs25487
or rs1799782 gene polymorphism and risk of female reproductive cancer risk was
found. These results should be validated in larger studies.
PMID- 28415706
TI - The role of targeted agents in the adjuvant treatment of colon cancer: a meta
analysis of randomized phase III studies and review.
AB - There has been debate as to whether targeted agents have beneficial effect when
added to adjuvant chemotherapy for patient with colon cancer. We conducted this
meta-analysis to investigate the role of targeted agents in the adjuvant
treatment of colon cancer. We searched PubMed, MEDLINE, EMBASE, and the Cochrane
Library databases. We included phase III trials with the data of disease-free
survival (DFS) and adverse events (AEs) of adjuvant treatment with targeted
agents. From 5 eligible studies, a total of 9,991 patients with resected colon
cancer were included in the meta-analysis of hazard ratio (HR) for 3-year DFS and
odds ratio (OR) for grade 3 or higher AEs. The addition of targeted agents showed
no improvement of 3-year DFS, compared to standard adjuvant chemotherapy alone
(HR = 1.04 [95% confidence interval (CI), 0.96-1.13], P = 0.31). In the subgroup
analysis according to the type of targeted agents, neither bevacizumab (HR = 1.03
[95% CI, 0.88-1.21], P = 0.72) nor cetuximab (HR = 1.11 [95% CI, 0.94-1.31], P =
0.22) was associated with improvement of DFS. Moreover, targeted agents
significantly increased grade 3 or higher AEs (OR = 1.73 [95% CI, 1.21-2.46], P =
0.003) and treatment-related death (OR = 2.15 [95% CI, 1.16-3.99], P = 0.02). In
conclusion, this meta-analysis demonstrates that the addition of targeted agents
to standard adjuvant chemotherapy results in no improvement of DFS with increased
severe AEs and treatment-related death in patients with resected colon cancer.
PMID- 28415707
TI - Luteolin reduces inflammation in Staphylococcus aureus-induced mastitis by
inhibiting NF-kB activation and MMPs expression.
AB - Mastitis is a serious and prevalent disease caused by infection by pathogens such
as Staphylococcus aureus. We evaluated the anti-inflammatory effects and
mechanism of luteolin, a natural flavonoid with a wide range of pharmacological
activities, in a mouse model of S. aureus mastitis. We also treated cultured
mouse mammary epithelial cells (mMECs) with S. aureus and luteolin.
Histopathological changes were examined by H&E staining and the levels of
inflammatory cytokine proteins were analyzed using ELISAs. We determined mRNA
levels with qPCR and the level of NF-kappaB and matrix metalloproteinase (MMP)
proteins by Western blotting. The observed histopathological changes showed that
luteolin protected mammary glands with S. aureus infection from tissue
destruction and inflammatory cell infiltration. Luteolin inhibited the expression
of TNF-alpha, IL-1beta, and IL-6, all of which were increased with S. aureus
infection of mammary tissues and mMECs. S. aureus-induced TLR2 and TLR4 was
suppressed by luteolin, as were levels of IkappaBalpha and NF-kappaB p65
phosphorylation and expression of MMP-2 and MMP-9. Levels of tissue inhibitor of
metalloproteinases (TIMP)-1 and TIMP-2 were enhanced. These findings suggest
luteolin is a potentially effective new treatment to reduce tissue damage and
inflammation from S. aureus-induced mastitis.
PMID- 28415708
TI - Human papillomavirus subtypes distribution among 2309 cervical cancer patients in
West China.
AB - OBJECTIVE: The prevalence of cervical Human Papillomavirus (HPV) infection in
cervical cancer varies greatly worldwide, and HPV prevalence and genotypes in
China are limited. The objective is to analyze the prevalence of HPV subtypes in
cervical cancer patients in west China as well as the relationships between
different histological types of cervical cancer and HPV subtypes. RESULTS: 2309
cases were included. 90.86% were infected with HPV, and the remaining 9.13% were
negative. The most common subtypes were HPV16, HPV18, HPV58, HPV53, and HPV33.
HPV16 and HPV18 appeared to be the most prevalent HPV subtypes across all age
groups, while the prevalence of the other subtypes varied between age groups. A
logistic regression analysis revealed that the occurrence of cervical squamous
cell carcinoma and adenocarcinoma was most closely correlated to a persistent
infection with HPV16 or HPV18, with P < 0.05. MATERIALS AND METHODS: The
prevalence of 27 HPV subtypes in 2309 cervical cancer patients who received
treatment at our hospital between June 2011 and January 2016 was analyzed based
on the results of HPV testing using Liquid suspension chip technology (Luminex
200). CONCLUSIONS: HPV16 and HPV18 were the most prevalent HPV subtypes among the
cervical cancer patients, followed by HPV58, HPV53, and HPV33. 9.13% of the cases
appeared to not be associated with HPV. This suggests that HPV testing without
the use of cytology may overlook some special types of cervical cancer that
account for approximately 10% of all cervical cancer cases.
PMID- 28415709
TI - A peptide derived from apoptin inhibits glioma growth.
AB - Glioblastoma (GBM) is associated with poor prognosis due to its resistance to
surgery, irradiation, and conventional chemotherapy. Thus, efficient therapeutic
approaches for the treatment of GBM are urgently needed. HSP70 is an
antiapoptotic protein that participates in the inhibition of both mitochondrial
and membrane receptor apoptosis pathways and is highly expressed in glioma
tissues. Here, we investigated a derivative of apoptin; specifically, a chicken
anemia viral protein with selective toxicity toward cancer cells that can inhibit
hyperactive molecules, including HSP70. Our earlier studies demonstrated that
apoptin directly binds to the promoter of HSP70 and inhibits HSP70 transcription,
which contributes to HSP70 downregulation. This study provides the first
demonstration of the therapeutic potential of an apoptin-derived peptide for the
treatment of GBM by identifying the minimal region of the apoptin domain required
for interaction with the heat-shock element (HSE). This apoptin-derived peptide
(ADP) inhibits glioma cell proliferation and tumor growth as well as exhibits an
increased ability to promote apoptosis in GBM cells compared with rapamycin and
temozolomide. ADP treatment inhibited xenograft tumor growth and increased the
overall health and survival of nude mice implanted with GBM cells. These effects
were measured in tumors obtained from cell lines and were observed in both
intracranial and subcutaneous xenografts. In conclusion, we provide the first
demonstration that ADP has therapeutic potential for the treatment of human GBM.
Specifically, this study suggests that ADP is a potent candidate for drug
development based on its favorable toxicity and pharmacokinetic profiles as well
as its time- and cost-saving benefits.
PMID- 28415710
TI - Marital status and survival of patients with oral cavity squamous cell carcinoma:
a population-based study.
AB - BACKGROUND: The relationship between marital status and oral cavity squamous cell
carcinoma (OCSCC) survival has not been explored. The objective of our study was
to evaluate the impact of marital status on OCSCC survival and investigate the
potential mechanisms. RESULTS: Married patients had better 5-year cancer-specific
survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs
41.1%). In multivariate Cox regression models, unmarried patients also showed
higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence
interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P
< 0.001). Multivariate logistic regression showed married patients were more
likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P <
0.001). Married patients still demonstrated better prognosis in the 1:1 matched
group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). MATERIALS AND METHODS:
11022 eligible OCSCC patients were identified from Surveillance, Epidemiology,
and End Results (SEER) database, including 5902 married and 5120 unmarried
individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards
regression model were used to analyze survival and mortality risk. Influence of
marital status on stage, age at diagnosis and selection of treatment was
determined by binomial and multinomial logistic regression. Propensity score
matching method was adopted to perform a 1:1 matched cohort. CONCLUSIONS:
Marriage has an independently protective effect on OCSCC survival. Earlier
diagnosis and more sufficient treatment are possible explanations. Besides, even
after 1:1 matching, survival advantage of married group still exists, indicating
that spousal support from other aspects may also play an important role.
PMID- 28415711
TI - Mutational analysis of multiple lung cancers: Discrimination between primary and
metastatic lung cancers by genomic profile.
AB - In cases of multiple lung cancers, individual tumors may represent either a
primary lung cancer or both primary and metastatic lung cancers. Treatment
selection varies depending on such features, and this discrimination is
critically important in predicting prognosis. The present study was undertaken to
determine the efficacy and validity of mutation analysis as a means of
determining whether multiple lung cancers are primary or metastatic in nature.
The study involved 12 patients who underwent surgery in our department for
multiple lung cancers between July 2014 and March 2016. Tumor cells were
collected from formalin-fixed paraffin-embedded tissues of the primary lesions by
using laser capture microdissection, and targeted sequencing of 53 lung cancer
related genes was performed. In surgically treated patients with multiple lung
cancers, the driver mutation profile differed among the individual tumors.
Meanwhile, in a case of a solitary lung tumor that appeared after surgery for
double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy
sample revealed a gene mutation profile consistent with the surgically resected
specimen, thus demonstrating that the tumor in this case was metastatic. In cases
of multiple lung cancers, the comparison of driver mutation profiles clarifies
the clonal origin of the tumors and enables discrimination between primary and
metastatic tumors.
PMID- 28415712
TI - Association analysis of telomere length related gene ACYP2 with the gastric
cancer risk in the northwest Chinese Han population.
AB - Gastric cancer (GC) is a complex multifactorial disease, and genetic factors are
believed the predominant cause to the occurrence of GC. We sought to investigate
the associations between single nucleotide polymorphisms (SNPs) in ACYP2 gene and
the risk of GC in the Northwest Chinese Han population. We recruited 302 GC cases
and 300 controls from northwest China and selected 13 SNPs from ACYP2 gene. SNPs
were genotyped using Sequenom Mass-ARRAY technology. Odds ratios (ORs) and 95 %
confidence intervals (CIs) were used to assess the association. Bonferroni's
multiple adjustment was applied to the level of significance, which was set at P
< 0.00078 (0.05/65). We found that the minor alleles of rs6713088, rs11125529,
rs12615793, rs843711, rs11896604, rs843706 and rs17045754 significantly
stimulated the risk of GC, and homozygous alleles of above SNPs except rs6713088
were also found increasing the GC risk (P < 0.05). Under additive model and
recessive model, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754
also activated the risk of GC (P < 0.05). However, after Bonferroni's multiple
adjusted was applied to our data, no SNP in our study was significantly related
to GC risk. Further results of haplotype analysis founds that the haplotypes
"TTCTAATG" (rs1682111, rs843752, rs10439478, rs843645, rs11125529, rs12615793,
rs843711, and rs11896604) and "AC" (rs843706 and rs17045754) were more frequency
among patients with GC, on the contrary, the haplotypes "CG" had a protective
role in the GC risk (P < 0.05). Our results indicate that ACYP2 polymorphisms may
influence the GC risk and may serve as a new precursory biomarker in the
northwest Chinese Han population.
PMID- 28415713
TI - miR-135a inhibits tumor metastasis and angiogenesis by targeting FAK pathway.
AB - Tumor metastasis has been the major cause of recurrence and death in patients
with gastric cancer. Here, we find miR-135a has a decreased expression in the
metastatic cell lines compared with its parental cell lines by analyzing microRNA
array. Further results show that miR-135a is downregulated in the majority of
human gastric cancer tissues and cell lines. Decreased expression of miR-135a is
associated with TNM stage and poor survival. Besides, regaining miR-135a in
gastric cancer cells obviously inhibits tumor growth, migration, invasion and
angiogenesis by targeting focal adhesion kinase (FAK) pathway. Bioinformatics
analysis and molecular experiments further prove that miR-135a is a novel
downstream gene of tumor suppressor p53. Blocking FAK with its inhibitor can also
enhance miR-135a expression through inducing p53. In summary, this study reveals
the expression and function of miR-135a in gastric cancer and uncovers a novel
regulatory mechanism of miR-135a.
PMID- 28415714
TI - Depth of response is a significant predictor for long-term outcome in advanced
gastric cancer patients treated with trastuzumab.
AB - PURPOSE: We aimed to determine and compare the predictive values of depth of
response (DpR) and early tumor shrinkage (ETS) on long-term outcomes in gastric
cancer patients treated with trastuzumab. RESULTS: From a total of 368 computed
tomography examinations, DpR and ETS were evaluated. DpR was a significant tumor
size metric in predicting PFS and OS, and showed better discriminatory ability
(higher Ctau indices, 0.6957 for PFS; 0.7191 for OS) than ETS. DpR >= 45% (vs. <
45%) was the optimal cutoff value, as it was best able to identify patients with
longer PFS (median 9.0 vs. 6.3 months, hazard ratio [HR] = 0.608; 95% confidence
interval [CI]: 0.335 to 1.104; P = 0.102) and OS (median 23.5 vs. 13.1 months, HR
= 0.441; 95% CI: 0.203 to 0.955; P = 0.038). MATERIALS AND METHODS: Sixty-one
gastric cancer patients who received first-line trastuzumab-based chemotherapy
were assessed for DpR and ETS. We employed Kaplan-Meier estimates, log-rank
tests, Cox proportional hazards regression models, time-dependent receiver
operating characteristics, and Youden's J index to evaluate and determine cutoff
values of DpR and ETS as predictors of progression-free survival (PFS) and
overall survival (OS). CONCLUSIONS: DpR and ETS were significant predictors of
long-term outcomes in gastric cancer patients treated with first-line
trastuzumab. Validation in prospective trials with larger patient populations is
needed.
PMID- 28415715
TI - Epha3 acts as proangiogenic factor in multiple myeloma.
AB - This study investigates the role of ephrin receptor A3 (EphA3) in the
angiogenesis of Multiple Myeloma (MM) and the effects of a selective target of
EphA3 by a specific monoclonal antibody on primary bone marrow endothelial cells
(ECs) of MM patients.EphA3 mRNA and protein were evaluated in ECs of MM patients
(MMECs), in ECs of patients with monoclonal gammopathies of undetermined
significance (MGECs) and in ECs of healthy subjects (control ECs). The effects of
EphA3 targeting by mRNA silencing (siRNA) or by the anti EphA3 antibody on the
angiogenesis were evaluated. We found that EphA3 is highly expressed in MMECs
compared to the other EC types. Loss of function of EphA3 by siRNA significantly
inhibited the ability of MMECs to adhere to fibronectin, to migrate and to form
tube like structures in vitro, without affecting cell proliferation or viability.
In addition, gene expression profiling showed that knockdown of EphA3 down
modulated some molecules that regulate adhesion, migration and invasion
processes. Interestingly, EphA3 targeting by an anti EphA3 antibody reduced all
the MMEC angiogenesis-related functions in vitro. In conclusion, our findings
suggest that EphA3 plays an important role in MM angiogenesis.
PMID- 28415716
TI - Single nucleotide polymorphism rs3124599 in Notch1 is associated with the risk of
lung cancer in northeast Chinese non-smoking females.
AB - Lung cancer is one of the most common cancers and the main cause of cancer
related deaths. Notch1 might play a part in tumorigenesis of lung cancer. Here we
explored the relationship of three SNPs (rs3124599, rs3124607 and rs3124594) in
Notch1 with the risk and the survival of lung cancer in non-smoking females,
including 556 cases and 395 controls. Chi-square tests, logistic regression
analysis and crossover analysis were conducted to estimate the association
between SNPs and the risk of lung cancer and the interaction between SNPs and
environmental exposure. Survival analysis was conducted to explore the
association between SNPs and survival of lung cancer. The results demonstrated
that the polymorphism of rs3124599 was associated with the susceptibility of lung
cancer in recessive model (AA+AG vs. GG). Compared to the those with AA or AG
genotype, individuals with GG genotype had a 1.562-fold increased risk of lung
cancer (P = 0.023, OR = 1.562, 95% CI = 1.062-2.297). In stratified analysis, the
GG genotype of rs3124599 would increase the risk of small cell lung cancer (SCLC)
(P = 0.011, OR = 2.167, 95% CI = 1.193-3.396). However, no significant
interaction between rs3124599 and cooking oil fume exposure was observed either
in addictive model or multiplicative model. The results of survival analysis
showed there was no significant association between SNPs and prognosis of lung
cancer (P = 0.949 for rs3124599, P = 0.508 for rs3124607, P = 0.884 for
rs3124594). Our study might indicate that rs312599 in Notch1 may be a novel
biomarker for SCLC risk in Chinese non-smoking females.
PMID- 28415717
TI - The imidazoacridinone C-1311 induces p53-dependent senescence or p53-independent
apoptosis and sensitizes cancer cells to radiation.
AB - C-1311 is a small molecule, which has shown promise in a number of pre-clinical
and clinical studies. However, the biological response to C-1311 exposure is
complicated and has been reported to involve a number of cell fates. Here, we
investigated the molecular signaling which determines the response to C-1311 in
both cancer and non-cancer cell lines. For the first time we demonstrate that the
tumor suppressor, p53 plays a key role in cell fate determination after C-1311
treatment. In the presence of wild-type p53, cells exposed to C-1311 entered
senescence. In contrast, cells lines without functional p53 underwent mitotic
catastrophe and apoptosis. C-1311 also induced autophagy in a non-p53-dependent
manner. Cells in hypoxic conditions also responded to C-1311 in a p53-dependent
manner, suggesting that our observations are physiologically relevant. Most
importantly, we show that C-1311 can be effectively combined with radiation to
improve the radiosensitivity of a panel of cancer cell lines. Together, our data
suggest that C-1311 warrants further clinical testing in combination with
radiotherapy for the treatment of solid tumors.
PMID- 28415718
TI - Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver
metastases in resected patients with colon cancer.
AB - Before reaching a peripheral vein (PV), miRNAs released by the tumor are diluted
and dispersed throughout the body or even retained in a specific organ. We
hypothesized that blood drawn from the tumor-draining vein could provide more
homogeneous information than blood drawn from the PV as that blood would contain
all the biomarkers released by the tumor before they reach a potential metastatic
site. We have profiled 754 miRNAs in 15 colon cancer plasma samples from the
tumor-draining vein, the mesenteric vein (MV), identifying 13 microRNAs
associated with relapse. The prognostic impact of these miRNAs were validated in
50 MV and 50 paired PV plasma samples of stage I-III colon cancer patients. Four
miRNAs, let-7g, miR-15b, miR-155 and miR-328, were found overexpressed in MV
compared to PV, and patients with high levels of those miRNAs in MV plasma had
shorter time to relapse. Interestingly, in patients developing liver metastases,
the exosomal cargo of miR-328 was much greater in MV than in PV plasma indicating
a possible role of miR-328 in the development of liver metastases. Our results
indicate that in colon cancer, the primary tumor releases high concentrations of
miRNAs through the MV, and some of them are contained in tumor derived exosomes.
PMID- 28415719
TI - Endosomal sorting and c-Cbl targeting of paxillin to autophagosomes regulate cell
matrix adhesion turnover in human breast cancer cells.
AB - Post-translational mechanisms regulating cell-matrix adhesion turnover during
cell locomotion are not fully elucidated. In this study, we uncovered an
essential role of Y118 site-specific tyrosine phosphorylation of paxillin, an
adapter protein of focal adhesion complexes, in paxillin recruitment to
autophagosomes to trigger turnover of peripheral focal adhesions in human breast
cancer cells. We demonstrate that the Rab-7 GTPase is a key upstream regulator of
late endosomal sorting of tyrosine118-phosphorylated paxillin, which is
subsequently recruited to autophagosomes via the cargo receptor c-Cbl.
Essentially, this recruitment involves a direct and selective interaction between
Y118-phospho-paxillin, c-Cbl, and LC3 and is independent from c-Cbl E3 ubiquitin
ligase activity. Interference with the Rab7-paxillin-autophagy regulatory network
using genetic and pharmacological approaches greatly impacted focal adhesion
stability, cell locomotion and progression to metastasis using a panel of human
breast cancer cells. Together, these results provide novel insights into the
requirement of phospho-site specific post-translational mechanism of paxillin for
autophagy targeting to regulate cell-matrix adhesion turnover and cell locomotion
in breast cancer cells.
PMID- 28415720
TI - The function of oxytocin: a potential biomarker for prostate cancer diagnosis and
promoter of prostate cancer.
AB - PURPOSE: To measure the level of oxytocin in serum and prostate cancer (PCa)
tissue and study its effect on the proliferation of PCa cells. RESULTS: Oxytocin
level in serum was significantly increased in PCa patients compared with the no
carcinoma individuals. Additionally, the levels of oxytocin and its receptor were
also elevated in the PCa tissue. However, no significant difference existed among
the PCa of various Gleason grades. Western blot analysis confirmed the previous
results and revealed an increased expression level of APPL1. MATERIALS AND
METHODS: The level of oxytocin in serum was measured by ELISA analysis. The
expression of oxytocin and its receptor in prostate was analyzed by
immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed
by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3
activity analysis, respectively. Western blot analysis was used for the detection
of PCNA, Caspase3 and APPL1 protein levels. CONCLUSIONS: Serum and prostatic
oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a
biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1
expression.
PMID- 28415721
TI - Robust in-silico identification of cancer cell lines based on next generation
sequencing.
AB - Cancer cell lines (CCL) are important tools for cancer researchers world-wide.
However, handling of cancer cell lines is error-prone, and critical errors such
as misidentification and cross-contamination occur more often than acceptable.
Based on the fact that CCL today very often are sequenced (partly or entirely)
anyway as part of the studies performed, we developed Uniquorn, a computational
method that reliably identifies CCL samples based on variant profiles derived
from whole exome or whole genome sequencing. Notably, Uniquorn does neither
require a particular sequencing technology nor downstream analysis pipeline but
works robustly across different NGS platforms and analysis steps. We evaluated
Uniquorn by comparing more than 1900 CCL profiles from three large CCL libraries,
embracing 1585 duplicates, against each other. In this setting, our method
achieves a sensitivity of 97% and specificity of 99%. Errors are strongly
associated to low quality mutation profiles. The R-package Uniquorn is freely
available as Bioconductor-package.
PMID- 28415722
TI - Stat3 phosphorylation is required for embryonic stem cells ground state
maintenance in 2i culture media.
AB - Embryonic stem cells (ES cells) can be maintained its undifferentiated state with
feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been
reported a new culture condition comprising serum-free medium with ERK and
GSK3beta inhibitors (2i) could drive ES cells into a state of pluripotency more
like inner cell mass (ICM) in mouse blastocysts called ground state. However,
although 2i could sustain ES cells self-renewal, LIF is routinely added. The
roles of Stat3 activation are still unclear now. Here we investigated whether
Jak/Stat3 might also contribute to the induction of ground state pluripotency. We
introduced a lentiviral construct with 7-repeat Stat3-binding sequence to drive
Renilla luciferase into ES cells, which can be used as a reporter to detect Stat3
activation by noninvasive bioluminescence imaging. Using this ES cells, we
investigated the role of Stat3 activation in ground state maintenance. The
results showed that Stat3 could be activated by 2i. Stattic, a chemical inhibitor
of Stat3 phosphorylation, could effectively inhibit Stat3 activation in ES cells.
When Stat3 activation was suppressed, ground state related genes were down
regulated, and ES cells could not be maintained the ground state pluripotency
even in 2i medium. All of these results indicate Stat3 activation is required in
ground state maintenance.
PMID- 28415723
TI - Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and
resulting overproduction of reactive oxygen species.
AB - Auranofin (AF) is an anti-arthritic drug considered for combined chemotherapy due
to its ability to impair the redox homeostasis in tumor cells. In this study, we
asked whether AF may in addition radiosensitize tumor cells by targeting
thioredoxin reductase (TrxR), a critical enzyme in the antioxidant defense system
operating through the reductive protein thioredoxin. Our principal findings in
murine 4T1 and EMT6 tumor cells are that AF at 3-10 MUM is a potent
radiosensitizer in vitro, and that at least two mechanisms are involved in TrxR
mediated radiosensitization. The first one is linked to an oxidative stress, as
scavenging of reactive oxygen species (ROS) by N-acetyl cysteine counteracted
radiosensitization. We also observed a decrease in mitochondrial oxygen
consumption with spared oxygen acting as a radiosensitizer under hypoxic
conditions. Overall, radiosensitization was accompanied by ROS overproduction,
mitochondrial dysfunction, DNA damage and apoptosis, a common mechanism
underlying both cytotoxic and antitumor effects of AF. In tumor-bearing mice, a
simultaneous disruption of the thioredoxin and glutathione systems by the
combination of AF and buthionine sulfoximine was shown to significantly improve
tumor radioresponse. In conclusion, our findings illuminate TrxR in cancer cells
as an exploitable radiobiological target and warrant further validation of AF in
combination with radiotherapy.
PMID- 28415724
TI - Pharmacological inhibition of Src kinase protects against acute kidney injury in
a murine model of renal ischemia/reperfusion.
AB - Activation of Src kinase has been implicated in the pathogenesis of acute brain,
liver, and lung injury. However, the role of Src in acute kidney injury (AKI)
remains unestablished. To address this, we evaluated the effects of Src
inhibition on renal dysfunction and pathological changes in a murine model of AKI
induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in
increased Src phosphorylation at tyrosine 416 (activation). Administration of
PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved
renal function and ameliorated renal pathological damage. PP1 treatment also
suppressed renal expression of neutrophil gelatinase-associated lipocalin and
reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented
downregulation of several adherens and tight junction proteins, including E
cadherin, ZO-1, and claudins-1/-4 in the kidney after I/R injury as well as in
cultured renal proximal tubular cells following oxidative stress. Finally, PP1
inhibited I/R-induced renal expression of matrix metalloproteinase-2 and -9,
phosphorylation of extracellular signal-regulated kinases1/2, signal transducer
and activator of transcription-3, and nuclear factor-kappaB, and the infiltration
of macrophages into the kidney. These data indicate that Src is a pivotal
mediator of renal epithelial injury and that its inhibition may have a
therapeutic potential to treat AKI.
PMID- 28415725
TI - Stat3-positive tumor cells contribute to vessels neoformation in primary central
nervous system lymphoma.
AB - With the aim of elucidating the relationship between Stat3 expression and tumor
vessels abnormalities in the PCNLs, in this study we evaluated Stat3 and pStat3
expression by Real-time PCR and by immunohistochemistry in biopsy sections from
PCNSL patients. Correlations of the expression levels with the presence of
aberrant vessels were analyzed by confocal laser microscopy analysis, using FVIII
as endothelial cell marker, CD133 and nestin as cancer stem cell (CSC) marker,
CD20 as tumor cell marker, and Stat3. In addition, we investigated Stat3
mutations in lymphoma cells to clarify the role of the constitutive expression of
Stat3 and of its phosphorylated forms. Results showed that in PCNSL, putative
endothelial cells lining the vessels are heterogeneous, expressing FVIII/
pStat3/CD133 (presumably originally they are vascular progenitor cells), as well
as FVIII/CD20/CD133 (presumably originally they are tumor cells). Finally, we
detected a fraction of the FVIII+ endothelial cell that co-expressed Stat3
bearing a tetraploid karyotype, while no amplification signal for the Stat3 gene
was detected.
PMID- 28415727
TI - Further rationale for optimal combined modality treatments.
PMID- 28415726
TI - PGE2/EP3/SRC signaling induces EGFR nuclear translocation and growth through EGFR
ligands release in lung adenocarcinoma cells.
AB - Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in
both tumor and stromal cells supporting tumor progression. Here we demonstrate
that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2
promotes nuclear translocation of epidermal growth factor receptor (nEGFR),
affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS
and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear
localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are
required for the effect of PGE2 on nEGFR and downstream signaling activities.
PGE2 binds its bona fide receptor EP3 which by activating SRC family kinases,
induces ADAMs activation which, in turn, releases EGFR-ligands from the cell
membrane and promotes nEGFR. Amphiregulin (AREG) and Epiregulin (EREG) appear to
be involved in nEGFR promoted by the PGE2/EP3-SRC axis. Pharmacological
inhibition or silencing of the PGE2/EP3/SRC-ADAMs signaling axis or EGFR ligands
i.e. AREG and EREG expression abolishes nEGFR induced by PGE2. In conclusion,
PGE2 induces NSCLC cell proliferation by EP3 receptor, SRC-ADAMs activation, EGFR
ligands shedding and finally, phosphorylation and nEGFR. Since nuclear EGFR is a
hallmark of cancer aggressiveness, our findings reveal a novel mechanism for the
contribution of PGE2 to tumor progression.
PMID- 28415728
TI - Lipid degradation promotes prostate cancer cell survival.
AB - Prostate cancer is the most common male cancer and androgen receptor (AR) is the
major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2)
is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2
expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2
encodes for an enzyme involved in lipid metabolism, and we use multiple
metabolite profiling platforms and RNA-seq to show that inhibition of ECI2
expression leads to decreased glucose utilization, accumulation of fatty acids
and down-regulation of cell cycle related genes. In normal cells, decrease in
fatty acid degradation is compensated by increased consumption of glucose, and
here we demonstrate that prostate cancer cells are not able to respond to
decreased fatty acid degradation. Instead, prostate cancer cells activate
incomplete autophagy, which is followed by activation of the cell death response.
Finally, we identified a clinically approved compound, perhexiline, which
inhibits fatty acid degradation, and replicates the major findings for ECI2
knockdown. This work shows that prostate cancer cells require lipid degradation
for survival and identifies a small molecule inhibitor with therapeutic
potential.
PMID- 28415729
TI - Association between hOGG1 polymorphism rs1052133 and gastric cancer.
AB - PURPOSE: To conduct a comprehensive evaluation of the association of the human8
oxoguanine glycosylase 1 (hOGG1) gene polymorphism rs1052133 with gastric cancer
(GC) through a systematic review and meta-analysis of genetic association study.
RESULTS: A total of 15 articles from published papers were included in our
analysis. The meta-analyses for hOGG1 rs1052133, composed of 4024GC patients and
6022controls, showed low heterogeneity for the included populations in all the
genetic models, except for the Caucasian population under allelic genetic model,
the Asian population under addictive model and Caucasian population under
dominant model. The analyses of all the genetic models in overall pooled
populations did not identify any significant association between GC and hOGG1
rs1052133 (Allelic model: C vs. G , p = 0.746; Addictive model: CC vs. GG, p =
0.888; Recessive model: CC +GC vs. GG, p = 0.628; Dominant model: CC vs. GG+GC, p
= 0.147), even though stratified analyses were conducted in different ethnicities
under each genetic model. MATERIALS AND METHODS: All case-control association
studies on hOGG1 and GC reported up to December 15, 2016 in PubMed, Embase, Web
of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs)
and 95% confidence intervals (95% CIs) were calculated for single-nucleotide
polymorphism (SNP) using fixed- and random- effects models according to between
study heterogeneity. Publication bias analyses were conducted using Begg test.
CONCLUSIONS: This meta-analysis showed there was no association between hOGG1
rs1052133 and GC. Given the limited sample size, further investigations including
more ethnic groups are required to validate the association.
PMID- 28415730
TI - A polymorphism at IGF1 locus is associated with anemia.
AB - In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis.
There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with
plasma IGF-1 levels. We investigated the effect of this polymorphism on
hemoglobin (Hb) concentration and anemia. The study group comprised 3286 adult
Whites. The rs35767 polymorphism was screened using a TaqMan allelic
discrimination assay. The rs35767 polymorphism was not associated with age,
gender, BMI, waist circumference, smoking, blood pressure, plasma glucose, HbA1c,
type 2 diabetes, HOMA-IR, hsCRP, eGFR, and lipid profile. Erythrocyte
sedimentation rate (ESR), fibrinogen, and fasting insulin levels were
significantly lower in TT genotype carriers compared with C allele carriers. Hb
concentration was significantly higher in carriers of the TT genotype compared
with C allele carriers, and a lower proportion of TT carriers had anemia. As
compared with TT genotype carriers, those bearing the CC genotype had a 2.4-fold
higher risk of anemia (OR 2.40, 95%CI 1.19-4.82), and those with the CT genotype
had a 2.0-fold higher risk of anemia (OR 2.06, 95%CI 1.04-4.11). The association
remained significant when fasting insulin, eGFR, smoking, diabetes, ACE
inhibitors, sartans or diuretics treatments, use of metformin and pioglitazone
were added to the model, but its independence was not retained after inclusion of
fibrinogen and ESR values into the model. In conclusion, rs35767 TT allele
carriers exhibited significantly higher concentrations of Hb, and lower risk of
anemia compared with C allele carriers supporting the idea that IGF-1 plays a
role in erythropoiesis homeostasis.
PMID- 28415734
TI - Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract
cancers: a systematic review and meta-analysis.
AB - BACKGROUND: Inflammation was considered to perform crucial roles in the
development and metastasis of malignancies. A heightened neutrophil-lymphocyte
ratio has been described to be associated with detrimental survivals in different
malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte
ratio on survivals in biliary tract cancer. The review evaluated the prognostic
value of neutrophil-lymphocyte ratio in biliary tract cancer. METHODS: MEDLINE,
the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically
searched for relevant articles. Associations between neutrophil-lymphocyte ratio
and long-term outcomes were expressed as the hazard ratios and 95% confidence
intervals. The odds ratio was utilized to assess the association between
neutrophil-lymphocyte ratio and clinicopathological parameters. RESULTS: Fourteen
studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high
pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low
pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened
pretreatment neutrophil-lymphocyte ratio was significantly associated with
detrimental overall survival and relapse free survival for biliary tract cancer
patients. In addition, elevated neutrophil-lymphocyte ratio was positively
correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and
greater lymph node involvement. CONCLUSION: This meta-analysis marked that an
increased pretreatment neutrophil-lymphocyte ratio was significantly linked with
detrimental long-term outcomes and clinicopathological parameters for patients
with biliary tract cancer.
PMID- 28415735
TI - Salicylate *Phenanthroline copper (II) complex induces apoptosis in triple
negative breast cancer cells.
AB - In this study, we investigated anti-tumor activity and associated molecular
mechanism of action of Salicylate ?Phenanthroline Copper (II) Complex in triple
negative breast cancer. Salicylate ?Phenanthroline Copper (II) Complex inhibited
the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20)
and induced apoptosis in a concentration-dependent manner. The effect was more
profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines.
Western blot showed that the expression of the apoptosis-related protein Bcl-2,
Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with
Salicylate ?Phenanthroline Copper (II) Complex. In vivo, Salicylate
?Phenanthroline Copper (II) Complex administration significantly attenuated tumor
growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and
survivin were reduced as measured by immunohistochemical staining. These data
suggest that Salicylate ?Phenanthroline Copper (II) Complex is a promising novel
therapeutic drug for triple-negative breast cancer and warrants further study.
PMID- 28415736
TI - The gamma-glutamyl transpeptidase to platelet ratio for non-invasive assessment
of liver fibrosis in patients with chronic hepatitis B and non-alcoholic fatty
liver disease.
AB - BACKGROUND/AIM: The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is a
novel serum model, which was reported more accurate than aspartate transaminase
to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)
for diagnosing significant fibrosis and cirrhosis in HBV mono-infection in West
Africa. We aimed to evaluate the diagnostic performance of GPR for liver fibrosis
in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease
(NAFLD). RESULTS: Of 131 patients, 41 (31.3%), 20 (15.3%), and 10 (7.6%) were
classified as having significant fibrosis, severe fibrosis and cirrhosis,
respectively. To predict significant fibrosis, the AUROC of GPR was higher than
that of APRI (0.86 vs 0.75, p = 0.001) and FIB-4 (0.86 vs 0.66, p < 0.001). To
predict severe fibrosis, the AUROC of GPR was also higher than that of APRI (0.89
vs 0.77, p = 0.002) and FIB-4 (0.89 vs 0.72, p = 0.001). To predict cirrhosis, no
difference was found between the AUROC of GPR and that of APRI (0.92 vs 0.86, p =
0.104). MATERIALS AND METHODS: 131 patients with CHB-NAFLD were included, and the
diagnostic performances of GPR, APRI and FIB-4 were compared by receiver
operating characteristic (ROC) curves and the area under ROC curves (AUROCs).
CONCLUSIONS: The GPR could be used as a non-invasive marker to predict liver
fibrosis and cirrhosis in CHB-NAFLD individuals.
PMID- 28415737
TI - Peroxynitrite dominates sodium nitroprusside-induced apoptosis in human
hepatocellular carcinoma cells.
AB - This study aims to explore which radicals dominate sodium nitroprusside (SNP)
induced cytotoxicity in human hepatocellular carcinoma (HCC) cells (HepG2 and
Hep3B). Exposure of SNP to cell medium produced abundant nitric oxide (NO),
superoxide anion (O2*-), hydrogen peroxide (H2O2) and iron ions. SNP potently
induced caspases activation, mitochondrial membrane permeabilization and
apoptosis in HCC cells. In Hep3B cells, pretreatment with NO scavenger (PTIO) did
not prevent SNP-induced cytotoxicity. However, in HepG2 cells, SNP-induced
cytotoxicity was prevented significantly by pretreatment with PTIO and O2*-
scavenger, and especially was almost completely blocked by pretreatment with
FeTPPS (peroxynitrite scavenger). In contrast, although H2O2 scavenger potently
scavenged SNP-induced H2O2 production, it did not prevent SNP-induced
cytotoxicity in HepG2 cells. In addition, pretreatment with DFO (iron ions
chelator) and iron-saturated DFO respectively completely prevented SNP-induced
cytotoxicity in HepG2 cells. Collectively, peroxynitrite from the reaction
between NO and O2*- elicited from SNP dominates the SNP-induced apoptosis of
HepG2 cells, in which both iron ions and H2O2 are not involved.
PMID- 28415738
TI - Tyrosine kinase inhibitor induced growth factor receptor upregulation enhances
the efficacy of near-infrared targeted photodynamic therapy in esophageal
adenocarcinoma cell lines.
AB - Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year
survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR
tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to
selectively treat malignant cells. In this in vitro report we demonstrate the
applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC),
using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX,
targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2).
Furthermore, we demonstrate that NIR-tPDT can be made more effective by tyrosine
kinase inhibitor (TKI) induced growth receptor upregulation. Together, these
results unveil a novel strategy for non-invasive EAC treatment, and by
pretreatment-induced receptor upregulation its future clinical application may be
optimized.
PMID- 28415739
TI - High TGF-beta1 expression predicts poor disease prognosis in hepatocellular
carcinoma patients.
AB - Transforming growth factor beta (TGF-beta) promotes the pathogenesis of
hepatocellular carcinoma (HCC). We evaluated the associations between TGF-beta1
expression and clinicopathological parameters in HCC patients from The Cancer
Genome Atlas (TCGA), as well as the prognostic power of TGF-beta1 expression.
Eligible studies were retrieved from several databases, and effects (hazard
ratios (HRs) with 95% confidence intervals (CIs)) for overall survival (OS),
disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free
survival (MFS), and progression-free survival (PFS) were pooled to assess the
prognostic ability of TGF-beta1 expression in HCC patients. Twelve qualified
articles and our TCGA data comprising 2,021 HCC patients were incorporated. In
the TCGA analysis, HCC patients with higher TGF-beta1 expression presented a
shorter OS than those with lower TGF-beta1 expression (HR = 1.42, p < 0.05). In
the meta-analysis, univariate analyses showed that HCC patients with higher TGF
beta1 expression had a shorter OS (pooling HR = 1.71, p < 0.01) and
DFS/RFS/MFS/PFS (pooling HR = 1.60, p < 0.01) than those with lower TGF-beta1
expression. In conclusion, our results suggested that high TGF-beta1 expression
promotes a poor prognosis in HCC patients.
PMID- 28415740
TI - Development and validation of nomograms for predicting survival in patients with
non-metastatic colorectal cancer.
AB - BACKGROUND: This study aimed to develop nomograms for predicting survival in
patients with non-metastatic colorectal cancer (CRC). RESULTS: On multivariate
analyses of the derivation set, the nomograms for OS and CSS shared common
significant prognostic factors: age, first-degree relative cancer history,
differentiation grade, vessels/nerves invasion, TNM stage, CEA, CA19-9 and PNI.
The nomograms displayed good accuracy in predicting OS and CSS, with C-indexes of
0.75 and 0.76, respectively. The calibration plots also showed an excellent
agreement between the predicted and observed survival probabilities. Furthermore,
the predictive accuracy of the nomograms was confirmed in the validation set,
with C-indexes of 0.79 and 0.83 for OS and CSS, respectively. MATERIALS AND
METHODS: On the basis of data from 822 patients with resected non-metastatic CRC,
nomograms for predicting overall survival (OS) and cancer-specific survival (CSS)
were established using Cox regression model. The predictive performance of the
nomograms was assessed by concordance index (C-index) and calibration plot. An
independent external cohort of 171 patients was used to validate the nomograms.
CONCLUSIONS: We developed and validated two nomograms for patients with non
metastatic CRC, which could provide individual prediction of OS and CSS with high
accuracy.
PMID- 28415743
TI - Survival differences of CIMP subtypes integrated with CNA information in human
breast cancer.
AB - CpG island methylator phenotype of breast cancer is associated with widespread
aberrant methylation at specified CpG islands and distinct patient outcomes.
However, the influence of copy number contributing to the prognosis of tumors
with different CpG island methylator phenotypes is still unclear. We analyzed
both genetic (copy number) and epigenetic alterations in 765 breast cancers from
The Cancer Genome Atlas data portal and got a panel of 15 biomarkers for copy
number and methylation status evaluation. The gene panel identified two groups
corresponding to distinct copy number profiles. In status of mere-loss copy
number, patients were faced with a greater risk if they presented a higher CpG
islands methylation pattern in biomarker panels. But for samples presenting
merely-gained copy number, higher methylation level of CpG islands was associated
with improved viability. In all, the integration of copy number alteration and
methylation information enhanced the classification power on prognosis. Moreover,
we found the molecular subtypes of breast cancer presented different
distributions in two CpG island methylation phenotypes. Generated by the same set
of human methylation 450K data, additional copy number information could provide
insights into survival prediction of cancers with less heterogeneity and might
help to determine the biomarkers for diagnosis and treatment for breast cancer
patients in a more personalized approach.
PMID- 28415741
TI - Enhancement of radiosensitivity by the novel anticancer quinolone derivative
vosaroxin in preclinical glioblastoma models.
AB - PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The
activity of vosaroxin, a first-in-class anticancer quinolone derivative that
intercalates DNA and inhibits topoisomerase II, was investigated in GBM
preclinical models as a single agent and combined with radiotherapy (RT).
RESULTS: Vosaroxin showed antitumor activity in clonogenic survival assays, with
IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments
exhibited significantly higher gammaH2Ax levels compared with controls. In
xenograft models, vosaroxin reduced tumor growth and showed enhanced activity
with RT; vosaroxin/RT combined was more effective than temozolomide/RT.
Vosaroxin/RT triggered rapid and massive cell death with characteristics of
necrosis. A minor proportion of treated cells underwent caspase-dependent
apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced
autophagy, increasing necrosis. This was associated with increased recruitment of
granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells.
Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin.
Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS)
significantly compared with RT, vosaroxin alone, temozolomide, and
temozolomide/RT in the U251-luciferase orthotopic model. MATERIALS AND METHODS:
Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined
with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in
U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in
orthotopic intrabrain models using luciferase-transfected U251 cells by
bioluminescence and magnetic resonance imaging. CONCLUSIONS: Vosaroxin
demonstrated significant activity in vitro and in vivo in GBM models, and showed
additive/synergistic activity when combined with RT in O6-methylguanine
methyltransferase-negative and -positive cell lines.
PMID- 28415744
TI - EMT-like circulating tumor cells in ovarian cancer patients are enriched by
platinum-based chemotherapy.
AB - BACKGROUND: Assuming that tumor cell dissemination requires a shift to a
mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal
transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients
and inquired, how their molecular phenotypes respond to platinum-based
chemotherapy and influence outcome. RESULTS: Before surgery, overall detection
rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed
(30%) and were mutually exclusive to epithelial CTCs in the majority of patients
(82%). After chemotherapy, EMT-like CTCs increased up to 52%, accompanied by the
"de novo" emergence of PI3Kalpha+/Twist+ EMT-like CTCs. Before surgery, PI3K+ EMT
like CTCs in combination with epithelial CTCs indicated decreased OS (p = 0.02)
and FIGO I-III patients with residual tumor burden after surgery were more likely
to be positive for EMT-like CTCs after chemotherapy (p = 0.02). In the latter
group, epithelial CTCs alone significantly correlated with decreased PFS and OS
(p = 0.02, p = 0.002), supported by an additional inclusion of PI3K+ CTCs (OS, p
= 0.001). MATERIALS AND METHODS: Blood samples of 91 ovarian cancer patients
before surgery and 31 matched samples after adjuvant chemotherapy were evaluated
for CTCs with the AdnaTest ovarian cancer and EMT-1, analyzing the epithelial
associated transcripts EpCAM, Muc-1 and CA125 and the EMT-associated transcripts
PI3Kalpha, Akt-2 and Twist. CONCLUSIONS: Platinum-based chemotherapy seems to
select for EMT-like CTCs in ovarian cancer patients and provokes a shift towards
PI3Kalpha and Twist expressing CTCs, which may reflect clonal tumor evolution
towards therapy resistance. It has to be determined, whether this CTC subgroup
may serve as a biomarker to identify patients at high risk.
PMID- 28415745
TI - Comparative study of cisplatin-based definitive concurrent chemoradiotherapy with
S-1 versus paclitaxel for unresectable locally advanced esophageal squamous cell
carcinoma.
AB - This study compared the efficiency and safety of definitive concurrent
chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus
Cisplatin (CS) in unresectable locally advanced esophageal squamous cell
carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients
were retrospectively reviewed. We performed a propensity score matching analysis;
41 patients treated with the CS regimen were matched 1:1 to patients who received
the TP regimen. Patient- and disease-related characteristics were well-balanced
between the two groups. The CS group showed significantly better treatment
compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49
days, P = 0.025) over the TP group during the CCRT course. The complete response
rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1-
and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4%
compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and
3-year progression-free survival (PFS) rates in the TP group were 51.2% and
24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The
incidence of severe and total neutropenia in the TP group was significantly
higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate
analysis revealed that T stage and the complete response rate were strong
prognostic factors associated with OS and PFS. In conclusion, both treatment
regimens yielded satisfactory survival outcomes, but the CS regimen could
significantly improve treatment compliance, reduce hematological toxicities and
lengths of hospital stay. Future prospective studies in large cohorts are highly
warranted to confirm the findings in our report.
PMID- 28415746
TI - Epigenetic up-regulation of ribosome biogenesis and more aggressive phenotype
triggered by the lack of the histone demethylase JHDM1B in mammary epithelial
cells.
AB - The alterations of ribosome biogenesis and protein synthesis play a direct role
in the development of tumors. The accessibility and transcription of ribosomal
genes is controlled at several levels, with their epigenetic regulation being one
of the most important. Here we explored the JmjC domain-containing histone
demethylase 1B (JHDM1B) function in the epigenetic control of rDNA transcription.
Since JHDM1B is a negative regulator of gene transcription, we focused on the
effects induced by JHDM1B knock-down (KD). We studied the consequences of stable
inducible JHDM1B silencing in cell lines derived from transformed and
untransformed mammary epithelial cells. In these cellular models, prolonged
JHDM1B downregulation triggered a surge of 45S pre-rRNA transcription and
processing, associated with a re-modulation of the H3K36me2 levels at rDNA loci
and with changes in DNA methylation of specific CpG sites in rDNA genes. We also
found that after JHDM1B KD, cells showed a higher ribosome content: which were
engaged in mRNA translation. JHDM1B KD and the consequent stimulation of
ribosomes biogenesis conferred more aggressive features to the tested cellular
models, which acquired a greater clonogenic, staminal and invasive potential.
Taken together, these data indicate that the reduction of JHDM1B leads to a more
aggressive cellular phenotype in mammary gland cells, by virtue of its negative
regulatory activity on ribosome biogenesis.
PMID- 28415747
TI - Comparison of Gadolinium-enhanced MRI and 18FDG PET/PET-CT for the diagnosis of
brain metastases in lung cancer patients: A meta-analysis of 5 prospective
studies.
AB - OBJECTIVE: We undertook this meta-analysis to compare the significance of
Gadolinium-enhanced MRI and 18FDG PET/PET-CT for diagnosing brain metastases of
lung cancer patients. RESULTS: Five articles comprising 941 patients were
included for analysis. The sensitivities with 95% confidence interval for PET/PET
CT and MRI were 0.21 (0.13 - 0.32) and 0.77 (95% CI = 0.60 - 0.89), specificities
were 1.00 (0.99 - 1.00) and 0.99 (0.97 - 1.00), and the areas under curve were
0.98 (0.96 - 0.89) and 0.97 (0.96 - 0.98). MATERIALS AND METHODS: A computerized
literature search of studies was conducted in the Pubmed and Embase databases.
Meta-analysis methods were used to calculate the sensitivities, specificities,
likelihood ratios ratios, diagnostic odd ratios, and areas under summary receiver
operating characteristic curves for PET/PET-CT and MRI, respectively.
CONCLUSIONS: The analysis suggested Gadolinium-enhanced MRI had higher
sensitivity than 18FDG PET/PET-CT for the diagnosis of brain metastases in lung
cancer. MRI may provide additional information to PET-CT for diagnosing brain
metastatic lesions.
PMID- 28415748
TI - The Spi1/PU.1 transcription factor accelerates replication fork progression by
increasing PP1 phosphatase in leukemia.
AB - Oncogenes trigger replicative stress that can lead to genetic instability, which
participates in cancer progression. Thus, determining how cells cope with
replicative stress can help our understanding of oncogenesis and lead to the
identification of new antitumor treatment targets. We previously showed that
constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads
to pre-leukemic cells that have a shortened S phase duration with an increased
replication fork speed and increased mutability in the absence of DNA breaks.
Here, we demonstrate that the S phase checkpoint protein CHK1 is maintained in a
low phosphorylation state in Spi1/PU.1-overexpressing cells and provide evidence
that this is not due to negative control of its primary kinase ATR. Notably, we
found that the expression of the CHK1 phosphatase PP1alpha is increased in
Spi1/PU.1-overexpressing cells. By exogenously modulating its activity, we
demonstrate that PP1alpha is required to maintain CHK1 in a dephosphorylated
state and, more importantly, that it is responsible for the accelerated
replication fork progression in Spi1/PU.1-overexpressing cells. These results
identify a novel pathway by which an oncogene influences replication in the
absence of DNA damage.
PMID- 28415749
TI - hMAGEA2 promotes progression of breast cancer by regulating Akt and Erk1/2
pathways.
AB - Breast cancer is the most abundant cancer worldwide and a severe problem for
women. Notably, breast cancer has a high mortality rate, mainly because of tumor
progression and metastasis. Triple-negative breast cancer (TNBC) is highly
progressive and lacks the expression of estrogen receptor (ER), progesterone
receptor (PR), and human epidermal growth factor receptor 2 (HER2). Therefore,
there are no established therapeutic targets against TNBC. In this study, we
investigated whether the expression of human melanoma-associated antigen A2
(MAGEA2) is associated with TNBC. We found that hMAGEA2 is significantly
overexpressed in human TNBC tissues; we also observed oncogenic properties using
TNBC cell lines (MDA-MB-231 and MDA-MB-468). The overexpression of hMAGEA2 in MDA
MB-231 cell line showed dramatically increased cellular proliferation, colony
formation, invasion, and xenograft tumor formation and growth. Conversely,
knockdown of hMAEGA2 in MDA-MB-468 cell line suppressed cellular proliferation,
colony formation, and xenograft tumor formation. Additionally, we showed that
hMAGEA2 regulated the activation of Akt and Erk1/2 signaling pathways. These data
indicate that hMAGEA2 is important for progression of TNBC and may serve as a
novel molecular therapeutic target.
PMID- 28415750
TI - Xanthohumol induces paraptosis of leukemia cells through p38 mitogen activated
protein kinase signaling pathway.
AB - Xanthohumol as a natural polyphenol demonstrates an anticancer activity, but its
underlying mechanism remains unclear. In this study, we showed that xanthohumol
(XN) induces paraptosis of leukemia cells. The paraptosis is one cell death which
is characterized by dilation of the endoplasmic reticulum and/or mitochondria.
The results demonstrated that XN treatment significantly inhibited cell
proliferation and triggered extensive cytoplasmic vacuolation of HL-60 leukemia
cells, but it did not cause the cleavage of caspase-3 protein or apoptosis. In
contrast, XN treatment resulted in LC3-II accumulation through blocking of
autophagosome maturation. Interestingly, the induction of cytoplasmic
vacuolization by XN is not associated with autophagy modulated by XN, therefore,
XN-induced cell death of HL-60 leukemia cells is not the classical apoptotic cell
death. Intriguingly, XN treatment triggered the dilatation of endoplasma
reticulum (ER) and induced ER stress by upregulating C/EBP homologous protein and
unfolded protein response regulator Grp78/Bip. Furthermore, XN treatment
triggered p38 mitogen activated protein kinase and its specific inhibitor
inhibited the paraptosis of HL-60 leukemia cells by XN. In conclusion, we for the
first time demonstrated that XN treatment can induce paraptosis of leukemia cells
through activation of p38 MAPK signaling.
PMID- 28415751
TI - Gene-gene interaction between PPARG and CYP1A1 gene on coronary artery disease in
the Chinese Han Population.
AB - AIMS: To observe the influence of the peroxisome proliferator-activator receptor
G (PPAR-G) gene and cytochrome P4501A1 (CYP1A1) single-nucleotide polymorphisms
(SNPs), and interactions among several SNPs on coronary artery disease (CAD)
risk. METHODS: A total of 1106 participants (including 583 males and 523 females)
including 550 CAD patients and 556 control subjects were recruited in this study,
and the mean age for these participants was 55.5 +/- 11.8 years old. Logistic
regression was used to observe association of SNP within PPARG and CYP1A1 with
CAD risk and GMDR model was used to screen the best interaction combinations.
RESULTS: CAD susceptibility was higher in those with homozygous mutant of
rs10865710, rs1805192 and rs4646903 than those with wild-type homozygotes, OR
(95%CI) were 1.47 (1.15-1.92), 1.69 (1.27-2.09) and 1.72 (1.35-2.32),
respectively. We also found a significant two-locus model involving rs1805192 and
rs4646903 (p = 0.0107), and the cross-validation consistency of this locus model
was 10 of 10, the testing accuracy of this model is 62.17%. Logistic regression
shown that CAD risk was the highest in those with rs1805192- Pro/Ala or Ala/Ala
and rs4646903- AG+GG genotype, and was lowest in those with rs1805192- Pro/ Pro
and rs4646903- AA genotype, OR(95%CI) = 3.56 (1.91-5.42). CONCLUSIONS:
Polymorphism in rs10865710, rs1805192 and rs4646903 and interaction between
rs1805192 and rs4646903 were related with increased CAD susceptibility.
PMID- 28415752
TI - Correlation between facial morphology and gene polymorphisms in the Uygur youth
population.
AB - Human facial morphology varies considerably among individuals and can be
influenced by gene polymorphisms. We explored the effects of single nucleotide
polymorphisms (SNPs) on facial features in the Uygur youth population of the
Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers,
and 10 SNPs previously associated with variations in facial physiognomy were
genotyped. In parallel, 3D images of the subjects' faces were obtained using
grating facial scanning technology. After delimitation of 15 salient landmarks,
the correlation between SNPs and the distances between facial landmark pairs was
assessed. Analysis of variance revealed that ENPP1 rs7754561 polymorphism was
significantly associated with RAla-RLipCn and RLipCn-Sbn linear distances (p =
0.044 and p = 0.012, respectively) as well as RLipCn-Stm curve distance (p =
0.042). The GHR rs6180 polymorphism correlated with RLipCn-Stm linear distance (p
= 0.04), while the GHR rs6184 polymorphism correlated with RLipCn-ULipP curve
distance (p = 0.047). The FGFR1 rs4647905 polymorphism was associated with LLipCn
Nsn linear distance (p = 0.042). These results reveal that ENPP1 and FGFR1
influence lower anterior face height, the distance from the upper lip to the
nasal floor, and lip shape. FGFR1 also influences the lower anterior face height,
while GHR is associated with the length and width of the lip.
PMID- 28415753
TI - High mobility group box 1 antagonist limits metastatic seeding in the lungs via
reduction of cell-cell adhesion.
AB - Metastatic spread is the leading cause for cancer-related mortality, with the
lungs being a major site for metastatic seeding. Available therapies for patients
with metastatic disease are extremely limited. Therefore, there is a desperate
need for new strategies to prevent or limit metastatic dissemination and treat
existing metastases. The metastatic cascade is highly complex and is affected by
multiple factors related to both tumor cells themselves and the microenvironment
in the future site of metastasis. We hypothesized that modifying the lung
microenvironment by blocking central ubiquitous signals may affect metastatic
seeding in the lungs. Given the high basal levels of the Receptor for Advanced
Glycation End products (RAGE) in the pulmonary tissue, and its pro-inflammatory
properties, we investigated the consequences of interfering with its ligand; High
Mobility Group Box 1 (HMGB1). To this end, we tested the effect of Carbenoxolone,
an HMGB1 antagonist, on primary tumor growth and metastatic progression in
several murine tumor models. We show that antagonizing HMGB1 prevents the
adhesion and colonization of cancer cells in the lungs through the reduction of
their adhesion and cell-cell interaction both in vitro and in vivo. We
demonstrated that these activities are mediated by downregulation of the adhesion
molecule Intercellular Adhesion Molecule 1 (ICAM1) and ultimately result in
reduced metastatic burden. Carbenoxolone decreases significantly lung metastases
formation and can be used potentially as prophylactic therapy for metastatic
diseases.
PMID- 28415754
TI - Gene-modified NK-92MI cells expressing a chimeric CD16-BB-zeta or CD64-BB-zeta
receptor exhibit enhanced cancer-killing ability in combination with therapeutic
antibody.
AB - Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated
immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC)
mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was
derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor
cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually
mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based
immunotherapy to cancer treatment, we designed and generated two chimeric
receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins.
The construct includes the low-affinity Fc receptor CD16 (158F) or the high
affinity Fc receptor CD64, with the addition of the CD8a extracellular domain,
CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the
signaling domain from CD3zeta. The resulting chimeric receptors, termed CD16-BB
zeta and CD64-BB-zeta, were used to generate modified NK-92MI cells expressing
the chimeric receptor, which were named NK-92MIhCD16 and NK-92MIhCD64 cells,
respectively. We found that NK-92MIhCD16 and NK-92MIhCD64 cells significantly
improved cytotoxicity against CD20-positive non-Hodgkin's lymphoma cells in the
presence of rituximab. These results suggest that the chimeric receptor
expressing NK-92MI cells may enhance the clinical responses to currently
available anticancer monoclonal antibodies.
PMID- 28415756
TI - Human melanoma cells resistant to MAPK inhibitors can be effectively targeted by
inhibition of the p90 ribosomal S6 kinase.
AB - The clinical availability of small molecule inhibitors specifically targeting
mutated BRAF marked a significant breakthrough in melanoma therapy. Despite a
dramatic anti-tumour activity and improved patient survival, rapidly emerging
resistance, however, greatly limits the clinical benefit. The majority of the
already described resistance mechanisms involve a reactivation of the MAPK
signalling pathway. The p90 ribosomal S6 kinase (RSK), a downstream effector of
the MAPK signalling cascade, has been reported to enhance survival of melanoma
cells in response to chemotherapy. Here, we can show that RSK activity is
significantly increased in human melanoma cells with acquired resistance to the
BRAFV600E/K inhibitor vemurafenib. Interestingly, inhibition of RSK signalling
markedly impairs the viability of vemurafenib resistant melanoma cells and is
effective both in two-dimensional and in three-dimensional culture systems,
especially in a chronic, long-term application. The effect of RSK inhibition can
be partly replicated by downregulation of the well-known RSK target, Y-box
binding protein 1 (YB-1). Intriguingly, RSK inhibition also retains its efficacy
in melanoma cells with combined resistance to vemurafenib and the MEK inhibitor
trametinib. These data suggest that active RSK signalling might be an attractive
novel therapeutic target in melanoma with acquired resistance to MAPK pathway
inhibitors.
PMID- 28415755
TI - Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in
glioblastoma.
AB - Malignant gliomas display high levels of the transcription factor c-myc and
organize a tumor specific chaperone network within mitochondria. Here, we show
that c-myc along with mitochondrial chaperone inhibition displays massive tumor
cell death. Inhibition of mitochondrial matrix chaperones and c-myc was
established by utilizing genetic as well as pharmacological approaches.
Bromodomain and extraterminal (BET) family protein inhibitors, JQ1 and OTX015,
were used for c-myc inhibition. Gamitrinib was applied to interfere with
mitochondrial matrix chaperones. A xenograft model was used to determine the in
vivo efficacy. Combined inhibition of c-myc and mitochondrial matrix chaperones
led to a synergistic reduction of cellular proliferation (CI values less than 1)
in established glioblastoma, patient-derived xenograft and stem cell-like glioma
cultures. The combinatorial treatment of BET inhibitors and Gamitrinib elicited
massive apoptosis induction with dissipation of mitochondrial membrane potential
and activation of caspases. Mechanistically, BET-inhibitors and Gamitrinib
mediated a pronounced integrated stress response with a PERK-dependent up
regulation of ATF4 and subsequent modulation of Bcl-2 family of proteins with
down-regulation of Mcl-1 and its interacting partner, Usp9X, and an increase in
pro-apoptotic Noxa. Blocking ATF4 by siRNA attenuated Gamitrinib/BET inhibitor
mediated increase of Noxa. Knockdown of Noxa and Bak protected from the
combinatorial treatment. Finally, the combination treatment of Gamitrinib and
OTX015 led to a significantly stronger reduction of tumor growth as compared to
single treatments in a xenograft model of human glioma without induction of
toxicity. Thus, Gamitrinib in combination with BET-inhibitors should be
considered for the development for clinical application.
PMID- 28415757
TI - An absence of platelet activation following thalidomide treatment in vitro or in
vivo.
AB - Increased risk of thromboembolism and platelet hyperreactivity has been reported
in patients receiving thalidomide therapy. Whether thalidomide induces platelet
activation directly or through other factors remains unclear. The aim of this
study was to evaluate the effect of thalidomide on platelet activation under
resting conditions in vitro and in vivo. Isolated human or mouse platelets were
treated with different concentrations of thalidomide (10, 50 and 100 MUg/ml) for
60 min at 37 degrees C followed by analysis of platelet surface expression of
platelet receptors GPIbalpha, GPVI, alphaIIbbeta3 and P-selectin, and PAC-1 or
fibrinogen binding, by flow cytometry and collagen- or ADP-induced platelet
aggregation. In addition, thalidomide (200 mg/kg) was intraperitoneally injected
into mice for analysis of the effect of thalidomide on platelet activation in
vivo. No increased expression of P-selectin, PAC-1 or fibrinogen binding was
observed in either human and mouse platelets after thalidomide treatment in vitro
for 60 min at 37oC. Thalidomide treatment also did not affect expression of
GPIbalpha, GPVI or alphaIIbbeta3, nor did it affect collagen- or ADP-induced
platelet aggregation at threshold concentrations. However, while mice injected
with thalidomide displayed no increased surface expression of platelet P-selectin
or alphaIIbbeta3, there was a significantly shortened tail bleeding time,
thrombin time, prothrombin time together with higher levels of Factor IX and
fibrinogen. In conclusion, thalidomide at therapeutic doses does not directly
induce platelet activation under resting conditions in vitro or in vivo, but
results in increased procoagulant activity, which could explain the thalidomide
dependent prothrombotic tendency in patients.
PMID- 28415758
TI - Differential microRNA expression profiling in primary tumors and matched liver
metastasis of patients with colorectal cancer.
AB - BACKGROUND: Liver metastasis is common in patients with colorectal cancer (CRC),
and is correlated with poor outcome. MicroRNAs (miRNAs) are small non-coding RNAs
involved in cancer development and progression, but their role in CRC liver
metastasis has not been extensively investigated. RESULTS: Thirteen miRNAs were
deregulated in pCRCs compared to their matched liver metastases. Seventeen miRNAs
were chosen for validation, which confirmed significantly reduced expression of
miR-99b-5p, miR-377 and miR-200c and increased expression of miR-196b-5p in the
tissue of liver metastasis. Furthermore, miR-200c and miR-196b-5p were positively
correlated with shorter overall survival in pCRC patients with liver metastasis.
MATERIALS AND METHODS: Firstly, affymetrix microarrays involving 1036 miRNAs were
performed in two pairs of primary CRCs (pCRCs) and their matched liver
metastases. Secondly, validation of the results was carried out on an independent
cohort of 48 pairs of pCRCs and matched liver metastases using quantitative real
time polymerase chain reaction assay. CONCLUSIONS: We discovered a pCRC liver
metastasis-specific miRNA panel including miR-377, miR-99b-5p, miR-200c and miR
196b-5p through intensive validation. These miRNAs may function as prognostic
factors in patients with metastatic CRC.
PMID- 28415759
TI - KSHV co-infection down-regulates HPV16 E6 and E7 from cervical cancer cells.
AB - High-risk human papillomavirus (HPV) infection is the etiological agent of some
malignancies such as cervical, oral and oropharyngeal cancers. Kaposi sarcoma
associated herpesvirus (KSHV) represents a principal causative agent of several
human cancers arising in those immunocompromised patients. Interestingly, KSHV
DNA has been detected in the oral cavity and the female genital tract, although
its detection rate in cervical samples is very low and few reports are about
KSHV/HPV co-infection. Therefore, it remains unclear about the role of KSHV co
infection in the development of HPV-related neoplasias. In the current study, we
report that HPV16-integrated cervical cancer cell-line SiHa is susceptible to
KSHV latent infection and replication. We also have found that KSHV infection or
viral latent proteins are capable of reducing HPV16 E6/E7 expression through the
manipulation of cellular microRNA function. Array analysis indicates that KSHV
infection induces some inflammatory cytokines/chemokines production as well as up
regulates a series of interferon-induced genes expression, which may facilitate
host immune defense system attacking these co-infected cells and clearance of
viruses. Together, our data have provided possible explanations for very low
detection rate of KSHV shedding as well as of KSHV/HPV co-infection in cervical
samples and/or cervical cancer cells.
PMID- 28415760
TI - Binding of galectin-1 to integrin beta1 potentiates drug resistance by promoting
survivin expression in breast cancer cells.
AB - Galectin-1 is a beta-galactoside binding protein secreted by many types of
aggressive cancer cells. Although many studies have focused on the role of
galectin-1 in cancer progression, relatively little attention has been paid to
galectin-1 as an extracellular therapeutic target. To elucidate the molecular
mechanisms underlying galectin-1-mediated cancer progression, we established
galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA)
against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB
231 and Hs578T. Ablation of galectin-1 expression decreased cell proliferation,
migration, invasion, and doxorubicin resistance. We found that these effects were
caused by decreased galectin-1-integrin beta1 interactions and suppression of the
downstream focal adhesion kinase (FAK)/c-Src pathway. We also found that
silencing of galectin-1 inhibited extracellular signal-regulated kinase
(ERK)/signal transducer and activator of transcription 3 (STAT3) signaling,
thereby down-regulating survivin expression. This finding implicates STAT3 as a
transcription factor for survivin. Finally, rescue of endogenous galectin-1 knock
down and recombinant galectin-1 treatment both recovered signaling through the
FAK/c-Src/ERK/STAT3/survivin pathway. Taken together, these results suggest that
extracellular galectin-1 contributes to cancer progression and doxorubicin
resistance in TNBC cells. These effects appear to be mediated by galectin-1
induced up-regulation of the integrin beta1/FAK/c-Src/ERK/STAT3/survivin pathway.
Our results imply that extracellular galectin-1 has potential as a therapeutic
target for triple-negative breast cancer.
PMID- 28415761
TI - YAP promotes tumorigenesis and cisplatin resistance in neuroblastoma.
AB - The transcriptional co-activator Yes-associated protein (YAP) is essential for
Hippo pathway-driven tumorigenesis in various cancers. However, the expression
and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was
highly expressed in Neuroblastoma (NB) and expression levels correlated with
advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma
proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP
inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor
growth by efficiently downregulating YAP expression in tumors. Additionally, less
proliferative and more apoptotic cells were found in the Peptide 17 treatment
group. Furthermore, YAP inhibition significantly inhibited cisplatin-resistant
neuroblastoma proliferation, tumorigenesis, and invasion in vitro. The
combination of Peptide 17 with low-dose cisplatin efficiently impaired cisplatin
resistant NB subcutaneous tumor growth, being as effective as high-dose
cisplatin. Notably, the combination therapy caused lesser liver toxicity in mice
compared to the high-dose cisplatin treatment group. Collectively, this work
identifies YAP as a novel regulator of neuroblastoma proliferation,
tumorigenesis, and invasion and indicates that YAP is a potential therapeutic
target for cisplatin-resistant neuroblastoma.
PMID- 28415763
TI - Low numbers of pre-leukemic fusion genes are frequently present in umbilical cord
blood without affecting DNA damage response.
AB - Despite widely accepted notion that many childhood leukemias are likely developed
from hematopoietic stem/progenitor cells (HSPC) with pre-leukemic fusion genes
(PFG) formed in embryonic/fetal development, the data on PFG incidence in
newborns are contradictive. To provide a better understanding of a prenatal
origin of leukemia, umbilical cord blood from 500 newborns was screened for the
presence of the most frequent PFG associated with pediatric B-cell acute
lymphoblastic leukemia. This screening revealed relatively high incidence of ETV6
RUNX1, BCR-ABL1 (p190) and MLL-AF4 at very low frequencies, averaging ~14 copies
per 100,000 cells. We assume that most of these PFG might originate relatively
late in embryonic/fetal development and will be eliminated later during postnatal
development. The obtained results suggested that higher PFG copy numbers
originating in specific time windows of the hematopoietic stem cell hierarchy may
define a better prognostic tool for the assessment of leukemogenic potential. We
have observed no significant effect of low-copy PFG on radiation-induced DNA
damage response, accumulation of endogenous DNA double-stranded breaks, and
apoptosis in either lymphocytes or HSPC. Imaging flow cytometry showed lower
level of gammaH2AX foci in HSPC in comparison to lymphocytes suggesting better
protection of HSPC from DNA damage.
PMID- 28415764
TI - Inhibitor of Tec kinase, LFM-A13, decreases pro-inflammatory mediators production
in LPS-stimulated RAW264.7 macrophages via NF-kappaB pathway.
AB - Tec kinase, a prototypical member of the Tec tyrosine kinases family, was shown
to mainly govern lymphocyte proliferation. In the present study, we investigated
the role of Tec kinase in acute inflammatory response in lipopolysaccharide (LPS)
challenge. First, we demonstrate that Tec kinase activity was observed in
RAW264.7 macrophages exposed to LPS. Tec and phosphorylated Tec expression were
upregulated in a dose- and time-dependent manner after LPS stimulation. LPS
increased monocyte chemotactic protein (MCP)-1 secretion and intercellular
adhesion molecule (ICAM)-1 expression, and increasing mRNA expression was
consistently observed. LPS also induced IkappaBalpha phoshporylaytion and its
degradation, increased NF-kappaB p65 phoshporylaytion and translocation to nuclei
in RAW264.7 cells. Pretreatment with LFM-A13 decreased LPS-induced cytokines and
chemokines production and mRNA levels, blocked NF-kappaB transactivation. These
effects of LPS were also prevented by Tec-siRNA. Additionally, LFM-A13 or Tec
siRNA obviously inhibited LPS-induced TGFbeta-activated kinase 1(TAK1)
phosphorylation. Taken together, our results suggest that Tec kinase involves in
acute inflammation process in LPS-stimulated RAW264.7 cells, at least mediated by
activating TAK1/ NF-kappaB signal pathway.
PMID- 28415765
TI - Stable aneuploid tumors cells are more sensitive to TTK inhibition than
chromosomally unstable cell lines.
AB - Inhibition of the spindle assembly checkpoint kinase TTK causes chromosome mis
segregation and tumor cell death. However, high levels of TTK correlate with
chromosomal instability (CIN), which can lead to aneuploidy. We show that
treatment of tumor cells with the selective small molecule TTK inhibitor NTRC
0066-0 overrides the mitotic checkpoint, irrespective of cell line sensitivity.
In stable aneuploid cells NTRC 0066-0 induced acute CIN, whereas in cells with
high levels of pre-existing CIN there was only a small additional fraction of
cells mis-segregating their chromosomes. In proliferation assays stable aneuploid
cells were more sensitive than cell lines with pre-existing CIN. Tetraploids are
thought to be an intermediate between diploid and unstable aneuploid cells. TTK
inhibitors had the same potency on post-tetraploid and parental diploid cells,
which is remarkable because the post-tetraploids are more resistant to mitotic
drugs. Finally, we confirm that the reference compound reversine is a TTK
inhibitor and like NTRC 0066-0, inhibits the proliferation of patient-derived
colorectal cancer organoids. In contrast, treatment with TTK inhibitor did not
reduce the viability of non-proliferating T cell acute lymphoblastic leukemia
cells samples. Consequently, TTK inhibitor therapy is expected to spare non
dividing cells, and may be used to target stable aneuploid tumors.
PMID- 28415766
TI - Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on
primary mammary ductal carcinoma cells revealing its therapeutic potential.
AB - Bacillus anthracis secretes three secretary proteins; lethal factor (LF),
protective antigen (PA) and edema factor (EF). The LF has ability to check
proliferation of mammary tumors, chiefly depending on mitogen activated protein
kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of
recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on
the primary mammary ductal carcinoma cells revealed significant (p < 0.01)
reduction in proliferation of tumor cells with mean inhibition indices of 28.0 +/
1.37% and 19.6 +/- 1.47% respectively. However, treatment with rPA alone had no
significant anti-proliferative effect as evident by low mean inhibition index of
3.4 +/- 3.87%. The higher inhibition index observed for rLF alone as compared to
LeTx is contrary to the existing knowledge on LF, which explains the requirement
of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible
existence of PA independent mode of action of LF including direct receptor
mediated endocytosis or modulation of signal transduction cascade via unknown
means is hypothesized. In silico protein docking analysis of other cellular
receptors for any plausibility to play the role of receptor for LF revealed c-Met
receptor showing strongest affinity for LF (H bond = 19; Free energy = -773.96),
followed by nerve growth factor receptor (NGFR) and human epidermal growth factor
receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic
molecule against primary mammary ductal carcinoma cells and also the c-Met as
potential alternative receptor for LF to mediate and modulate PA independent
signal transduction.
PMID- 28415767
TI - Unique properties of thymic antigen-presenting cells promote epigenetic
imprinting of alloantigen-specific regulatory T cells.
AB - Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce
transplantation tolerance. However, stability of Tregs still remains contentious
and may potentially restrict their clinical use. Recent work suggested that
epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial
for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these
events are initiated already during early stages of thymic Treg development.
However, the mechanisms governing this process remain largely unknown. Here we
demonstrate that thymic antigen-presenting cells (APCs), including thymic
dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs), can induce
a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic
signature genes in developing Tregs when compared to splenic DCs (sp-DCs).
Transcriptomic profiling of APCs revealed differential expression of secreted
factors and costimulatory molecules, however neither addition of conditioned
media nor interference with costimulatory signals affected Foxp3 induction by
thymic APCs in vitro. Importantly, when tested in vivo both mTEC- and t-DC
generated alloantigen-specific Tregs displayed significantly higher efficacy in
prolonging skin allograft acceptance when compared to Tregs generated by sp-DCs.
Our results draw attention to unique properties of thymic APCs in initiating
commitment towards stable and functional Tregs, a finding that could be highly
beneficial in clinical immunotherapy.
PMID- 28415769
TI - Aurora kinase B dependent phosphorylation of 53BP1 is required for resolving
merotelic kinetochore-microtubule attachment errors during mitosis.
AB - Defects in resolving kinetochore-microtubule attachment mistakes during mitosis
is linked to chromosome instability associated with carcinogenesis as well as
resistance to cancer therapy. Here we report for the first time that tumor
suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342)
by Aurora kinase B both in vitro and in human cells, which is required for
optimal recruitment of 53BP1 at kinetochores. Furthermore, 53BP1 staining
normally localized on the outer kinetochore, extended to the whole kinetochore
when it is merotelically-attached, in concert with mitotic centromere-associated
kinesin. Kinetochore-binding of pS1342-53BP1 is essential for efficient resolving
of merotelic attachment, a spontaneous kinetochore-microtubule connection error
that usually causes aneuploidy. Consistently, loss of 53BP1 results in
significant increase in lagging chromosome events, micronuclei formation and
aneuploidy, due to the unresolved merotely in both cancer and primary cells,
which is prevented by ectopic wild type 53BP1 but not by the nonphophorylable
S1342A mutant. We thus document a novel DNA damage-independent function of 53BP1
in maintaining faithful chromosome segregation during mitosis.
PMID- 28415770
TI - Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk:
updated meta-analysis.
AB - Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been
reported to have a relationship with the risk of the development of various
cancers. Many studies have described the influence of Ser326Cys polymorphism of
the hOGG1 gene on cancer susceptibility. However, the results have remained
inconclusive and controversial. Therefore, we performed a meta-analysis to more
precisely determine the relationship between the hOGG1 polymorphism and the
development of cancer.Electronic databases including PubMed, Embase, Google
Scholar, and the Korean Studies Information Service System (KISS) were searched.
The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to
assess the strength of the association with the risk of cancer using
Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies
including 38,757 cancer patients and 50,177 control subjects were analyzed for
the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys
polymorphism of the hOGG1 gene statistically increased the susceptibility of
cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR
= 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI =
1.033-1.179, p = 0.002). Also, other genotype models showed significant
association with cancer (p < 0.05, respectively).The present meta-analysis
concluded that the G allele was associated with an increased risk of cancer. It
suggested that the hOGG1 polymorphism may be a candidate marker of cancer.
PMID- 28415772
TI - Endoscopic therapy for patients with pancreaticobiliary maljunction: a follow-up
study.
AB - BACKGROUND: Data on the experience of endoscopic retrograde
cholangiopancreatography (ERCP) in the management of pancreaticobiliary
maljunction (PBM) is limited. METHODS: A retrospective review of patients with
PBM who underwent therapeutic ERCP at our endoscopy center between January 2008
and January 2016 was performed. Demographic, clinical, radiological and
endoscopic data was documented. Patients who underwent sphincterotomy were
divided into dilated group and undilated group based on their common channel
diameter. RESULTS: Sixty-three PBM patients underwent 74 ERCP procedures. The
technical success rate was 97.3%. ERCP therapy significantly decreased the levels
of elevated liver enzymes and bilirubin. After an average of 27 months follow-up,
7 patients (11.1%) were lost. The overall effective rate of ERCP therapy was
60.7% (34/56). Decline in severity and frequency of abdominal pain was
significant. Procedure-related complications were observed in 5 (6.8%) cases.
Between the dilated group and undilated group, no significant difference was
observed in effective rate, adverse events and follow-up results. CONCLUSIONS:
ERCP can serve as a transitional step to stabilize PBM patients before definitive
surgery. PBM patients with undilated common channel could benefit from
sphincterotomy as well as those with dilated common channel.
PMID- 28415773
TI - Effects of CD20+ B-cell infiltration into allografts on kidney transplantation
outcomes: a systematic review and meta-analysis.
AB - The effects of CD20+ B-cell infiltration during acute rejection on graft outcomes
are controversial. The objective of this systematic review and meta-analysis was
to clarify this issue. We performed a systematic literature search for studies
published up to January 14, 2016. A total of 5 studies, with 200 patients, were
included. The presence of CD20+ B cells in renal biopsies during allograft
rejection was associated with graft loss and steroid resistance. No association
of CD20+ B-cell infiltration with C4d-positive staining of the peritubular
capillaries in renal biopsies was found in the analysis of patients who
experienced kidney graft rejection. In conclusion, CD 20+ B cell infiltration
during allograft rejection was associated with an increased risk of graft loss
and steroid resistance.
PMID- 28415774
TI - Chemoprevention of prostate cancer in men with high-grade prostatic
intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect
treatment comparison.
AB - BACKGROUND: High-grade prostatic intraepithelial neoplasia (HGPIN) is the
precursor or premalignant form of prostate cancer. At least 30% patients with a
confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy.
HGPIN patients are the appropriate at-risk population for chemoprevention
strategies investigation against prostate cancer. However the commonly used
chemoprevention agents that targeted on hormonal imbalance or lifestyle-related
factors showed varied results in HGPIN patients. METHODS: Literature searches
were conducted in PubMed, EMBASE and Cochrane library according to Cochrane
guidelines before January 31st, 2017. Direct meta-analysis were performed to
summarize the efficacy of candidate chemopreventative agents Dutasteride,
Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food
products combination. Adjusted indirect meta-analyses were employed to compare
the relative efficacy of these candidate chemoprevention agents head-to-head.
RESULTS: The overall incidence of prostate cancer in HGPIN was slightly decreased
by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P =
0.183), with minor heterogeneity (I2 = 22.3%, d???2 = 15.08, P = 0.237), but
without statistical significance. Subgroup analysis showed that green tea
catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs
23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity
(I2 = 47.9%, d???2 = 1.92, P = 0.166). The adjusted indirect meta-analysis
favored green tea catechins over other chemoprevention agents, and significantly
when compared to natural food products combination (RR = 0.355, 95% CI: 0.134
0.934). CONCLUSION: The overall efficacy of chemoprevention agents in HGPIN
patients is limited. But Green tea catechins showed the superiority to decrease
prostate cancer in HGPIN patients.
PMID- 28415775
TI - Adverse genomic alterations and stemness features are induced by field
cancerization in the microenvironment of hepatocellular carcinomas.
AB - Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver
tissues. The resulting regenerative and inflammatory processes create an adverse
milieu that promotes tumor-initiation and progression. A better understanding of
the hepatic tumor-microenvironment interaction might infer profound therapeutic
implications.Integrative whole genome and transcriptome analyses of different
tumor regions, the invasive tumor border and tumor-surrounding liver (SL) were
performed to identify associated molecular alterations and integrated with our
existing HCC database. Expression levels and localization of established CSC
markers were assessed in pre-neoplastic lesions and confirmed in two independent
patient cohorts using qRT-PCR, immunohistochemistry and immunofluorescence.Our
results indicate that genomic and transcriptomic profiles between SL and
different tumor regions are quite distinct. Progressive increase in genetic
alterations and activation of pathways related to proliferation as well as
apoptosis were observed in the tumor tissue, while activation of stemness markers
was present in cirrhotic SL and continuously decreased from pre-neoplastic
lesions to HCC. Interestingly, the invasive tumor border was characterized by
inflammatory and EMT-related gene sets as well as activation of pro-survival
signaling. Consistently, integration of gene expression signatures with two
independent HCC databases containing 300 HCCs revealed that border signatures are
predictive of HCC patient survival.Prognostic significance of the permissive
liver microenvironment might be a consequence of a pro-oncogenic field effect
that is caused by chronic regenerative processes. Activation of key oncogenic
features and immune-response signaling indicates that the cross-talk between
tumor and microenvironment might be a promising therapeutic and/or preventive
target.
PMID- 28415776
TI - Targeting protein homeostasis with nelfinavir/salinomycin dual therapy
effectively induces death of mTORC1 hyperactive cells.
AB - Uncontrolled cell growth in Tuberous Sclerosis Complex occurs due to
inappropriate activation of mechanistic (mammalian) target of rapamycin complex 1
(mTORC1). The current therapy, rapamycin, produced promising clinical trial
results, but patient tumours regrow if treatment is discontinued, revealing
rapamycin has cytostatic properties rather than a cytotoxic effect. Taking
advantage of the enhanced levels of endoplasmic reticulum (ER) stress present in
TSC2-null cells, we investigated drug combinations producing a cytotoxic
response. We found a nelfinavir and salinomycin combination specifically killed
TSC2-deficient, mTORC1 hyperactive cells. Cytotoxicity was rescued by reducing
protein synthesis, either through mTORC1 inhibition or cycloheximide treatment.
This indicates that the drug combination targets the cells by tipping the protein
homeostasis balance of the already metabolically stressed TSC2-deficient cells in
favour of cell death. Furthermore, this drug combination also inhibited tumour
formation in TSC2-deficient cell models and caused tumour spheroid death in 3D
culture. Importantly, the 3D assay could differentiate the cytostatic agent,
rapamycin, from the cytotoxic nelfinavir/salinomycin combination. Sporadic cancer
cell lines with hyperactive mTORC1 signalling were also susceptible to this
nelfinavir/salinomycin drug combination. This work indicates that the protein
homeostasis pathway is an attractive therapeutic target in both Tuberous
Sclerosis Complex and mTORC1-driven sporadic cancers.
PMID- 28415779
TI - Relationship of p73 gene polymorphism and additional gene-smoking and gene
obesity interaction with non-small cell lung cancer risk.
AB - AIM: The aim of this study was to investigate the impact of G4C14-to-A4T14
polymorphism within P73 gene and additional interactions with current smoking and
obesity on non-small cell lung cancer (NSCLC) risk in a Chinese population.
RESULTS: Logistic regression analysis showed a significant association between
genotypes of the AT allele in G4C14-to-A4T14 and decreased NSCLC risk. NSCLC risk
was significantly lower in carriers of the G4C14-to-A4T14- AT allele than those
with GC/GC genotype (AT/AT + GC/AT versus GC/GC), adjusted OR (95%CI) = 0.68
(0.55-0.93). We also found that the OR (95%CI) was 1.88 (1.32-2.47) for current
smokers compared with never smokers and 0.69 (0.40-0.95) for obese subjects
compared to participants with normal BMI. Never smokers with AT/AT or GC/AT of
the G4C14-to-A4T14 genotype have the lowest NSCLC risk compared with smokers with
the GC/GC genotype after covariates adjustment, OR (95%CI) = 0.52 (0.26-0.87).
Obese participants with G4C14-to-A4T14- AT/AT or GC/AT genotype have the lowest
NSCLC risk compared with non- obese subjects with the GC/GC genotype after
adjusting for covariates, OR (95% CI) = 0.56 (0.33-0.85). MATERIALS AND METHODS:
A logistic regression model was used to examine the association between G4C14-to
A4T14 polymorphism and NSCLC, and its interaction with current smoking and
obesity. The odds ratios (OR) and 95% confident intervals (95%CI) were
calculated. CONCLUSIONS: Our results support an important association between the
G4C14-to-A4T14 and decreased NSCLC risk and additional impact of an interaction
between G4C14-to-A4T14 and smoking or obesity on NSCLC risk.
PMID- 28415780
TI - Long noncoding RNA PCAT-14 induces proliferation and invasion by hepatocellular
carcinoma cells by inducing methylation of miR-372.
AB - Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of
CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is
overexpressed in patients with hepatocellular carcinoma (HCC), and is associated
with a poor prognosis after surgery. Our results demonstrate that PCAT-14
promotes proliferation, invasion, and cell cycle arrest in HCC cells. In
addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR
372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on
proliferation, invasion, and cell cycle in HCC cells. Moreover, PCAT-14 regulates
expression of ATAD2 and activation of the Hedgehog pathway via miR-372. These
findings indicate that PCAT-14 plays an important role in HCC, and may serve as a
novel prognostic factor and therapeutic target.
PMID- 28415781
TI - Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.
AB - Variations in DNA repair genes have been reported as key factors in gastric
cancer (GC) susceptibility but results among studies are inconsistent. We aimed
to assess the relevance of DNA repair gene polymorphisms and environmental
factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA
from 603 patients with primary GC and 603 healthy controls was typed for 123
single nucleotide polymorphisms in DNA repair genes using the Illumina platform.
Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95%
confidence interval (CI): 1.55-2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22
2.57), and family history of GC (OR: 2.87; 95% CI: 1.85-4.45) were identified as
independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95%
CI: 0.56-0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56-0.96), and BRIP1
rs4986764T (OR: 0.55; 95% CI: 0.38-0.78) variants were associated with lower GC
risk. Significant associations with specific anatomopathological GC subtypes were
also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G,
and rs3136038T variants being inversely associated with cardia GC risk. Moreover,
the XRCC3 rs861528 allele A was significantly increased in the patient subgroup
with diffuse GC (OR: 1.75; 95% CI: 1.30-2.37). Our data show that specific TP53,
BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk
and specific subtypes in Caucasians.
PMID- 28415782
TI - Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple
myeloma cells.
AB - Curative responses in the treatment of multiple myeloma (MM) are limited by the
emergence of therapeutic resistance. To address this problem, we set out to
identify druggable mechanisms that convey resistance to proteasome inhibitors
(PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In
isogenic pairs of PI sensitive and resistant cells, we observed stark differences
in cellular bioenergetics between the divergent phenotypes. PI resistant cells
exhibited increased mitochondrial respiration driven by glutamine as the
principle fuel source. To target glutamine-induced respiration in PI resistant
cells, we utilized the glutaminase-1 inhibitor, CB-839. CB-839 inhibited
mitochondrial respiration and was more cytotoxic in PI resistant cells as a
single agent. Furthermore, we found that CB-839 synergistically enhanced the
activity of multiple PIs with the most dramatic synergy being observed with
carfilzomib (Crflz), which was confirmed in a panel of genetically diverse PI
sensitive and resistant MM cells. Mechanistically, CB-839 enhanced Crflz-induced
ER stress and apoptosis, characterized by a robust induction of ATF4 and CHOP and
the activation of caspases. Our findings suggest that the acquisition of PI
resistance involves adaptations in cellular bioenergetics, supporting the
combination of CB-839 with Crflz for the treatment of refractory MM.
PMID- 28415783
TI - Mass spectral analysis of the multikinase inhibitor BZG and its metabolites and
analysis of their binding to vascular endothelial growth factor receptor-2.
AB - We previously showed that BZG is a novel multitarget kinase inhibitor, which
inhibited hepatocellular carcinoma in vivo and in vitro. In the present study, we
used ultra-performance liquid chromatography coupled with quadrupole time-of
flight mass spectrometry (UPLC/Q-TOF MS) to characterize BZG and its metabolites
generated in vivo. The probable metabolic mechanism was further confirmed by
analysis of Phase I and Phase II metabolism in liver microsomes and with
recombinant enzymes. In addition, the binding affinities of BZG metabolites to
vascular endothelial growth factor receptor 2 (VEGFR2) were predicted using
electronic high throughput screening (eHiTS). The results showed that BZG
underwent phase I and phase II metabolism. We detected 11 BZG metabolites and
identified hydroxylation, glucuronation, acetylation, sulfonation and degradation
as the major metabolic processes in vivo and in vitro. Five of the eleven
metabolites showed highly favorable eHiTS energy scores that were lower than
sorafenib. Knowledge of the in vivo metabolic pathways of BZG and its binding
affinities to VEGFR2 will be beneficial for further clinical development of BZG.
PMID- 28415784
TI - Misregulation of DNA damage repair pathways in HPV-positive head and neck
squamous cell carcinoma contributes to cellular radiosensitivity.
AB - Patients with human papillomavirus type 16 (HPV)-associated oropharyngeal
squamous cell carcinomas (OPSCC) display increased sensitivity to radiotherapy
and improved survival rates in comparison to HPV-negative forms of the disease.
However the cellular mechanisms responsible for this characteristic difference
are unclear. Here, we have investigated the contribution of DNA damage repair
pathways to the in vitro radiosensitivity of OPSCC cell lines. We demonstrate
that two HPV-positive OPSCC cells are indeed more radiosensitive than two HPV
negative OPSCC cells, which correlates with reduced efficiency for the repair of
ionising radiation (IR)-induced DNA double strand breaks (DSB). Interestingly, we
show that HPV-positive OPSCC cells consequently have upregulated levels of the
proteins XRCC1, DNA polymerase beta, PNKP and PARP-1 which are involved in base
excision repair (BER) and single strand break (SSB) repair. This translates to an
increased capacity and efficiency for the repair of DNA base damage and SSBs in
these cells. In addition, we demonstrate that HPV-positive but interestingly more
so HPV-negative OPSCC display increased radiosensitivity in combination with the
PARP inhibitor olaparib. This suggests that PARP inhibition in combination with
radiotherapy may be an effective treatment for both forms of OPSCC, particularly
for HPV-negative OPSCC which is relatively radioresistant.
PMID- 28415785
TI - The role of nitric oxide pathway in arginine transport and growth of IPEC-1
cells.
AB - L-Arginine itself and its metabolite-nitric oxide play great roles in intestinal
physiology. However, the molecular mechanism underlying nitric oxide pathway
regulating L-Arginine transport and cell growth is not yet fully understood. We
report that inhibition of nitric oxide synthase (NOS) significantly induced cell
apoptosis (p < 0.05), and promoted the rate of Arginine uptake and the
expressions of protein for CAT-2 and y+LAT-1 (p < 0.05), while reduced protein
expression of CAT-1. And NOS inhibition markedly decreased the activation of
mammalian target of rapamycin (mTOR) and PI3K-Akt pathways by Arginine in the
IPEC-1 cells (p < 0.05). Taken together, these data suggest that inhibition of NO
pathway by L-NAME induces a negative feedback increasing of Arginine uptake and
CAT-2 and y+LAT-1 protein expression, but promotes cell apoptosis which involved
inhibiting the activation of mTOR and PI3K-Akt pathways.
PMID- 28415786
TI - Arterial stiffness and blood pressure improvement in aldosterone-producing
adenoma harboring KCNJ5 mutations after adrenalectomy.
AB - The aim of this study was to show the effect of KCNJ5 mutational status on
arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between
February 2008 and January 2010, we prospectively enrolled 108 aldosterone
producing adenoma patients undergoing adrenalectomy. We conducted repeated
measurements of pulse wave velocity at baseline, 6 months, and 12 months after
adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial
stiffness and risk for hypertension at 12 months after adrenalectomy were
analyzed after propensity score matching in a 1:1 ratio. After matching for age,
sex and body mass index, 88 patients were divided equally into KCNJ5-mutant and
non-mutant groups. KCNJ5 mutational status was not an independent variable in
either the generalized estimating equation model (p = 0.147) or the percentage
change of brachial-ankle pulse wave velocity (p = 0.106). The generalized
additive model smoothing plot showed that aldosterone-producing adenoma patients
who carried the KCNJ5 mutation and were aged between 37 and 60 may have a
hypertension recovery advantage. According to our observations during a 12-month
follow-up after adrenalectomy, KCNJ5 mutational status was not associated with
improvement in arterial stiffness.
PMID- 28415787
TI - Knockdown of P4HA1 inhibits neovascularization via targeting glioma stem cell
endothelial cell transdifferentiation and disrupting vascular basement membrane.
AB - Emerging evidence has demonstrated transdifferentiation process of glioma stem
cells (GSCs) into endothelial cells (ECs) in glioma neovascularization. Herein,
we focused on screening for genes that were differentially expressed in the
transdifferentiation process using microarray analysis. Bioinformatics analysis
revealed differential expression of the prolyl 4-hydroxylase subunit alpha-1
(P4HA1) gene. We determined that P4HA1 expression was correlated with
histological grade, the level of Ki67 and microvessel density (MVD) in human
glioma specimens. Knockdown of P4HA1 inhibited the proliferation, migration and
tube formation of GSCs in vitro. In vivo studies revealed that the downregulation
of P4HA1 inhibited intracranial tumor growth, prolonged the overall survival time
of xenograft mice and suppressed the neovascularization in brain tumors.
Moreover, P4HA1 regulates the expression of vascular endothelial growth factor A
(VEGF-A), especially an anti-angiogenic isoform-VEGF165b. Additionally, knockdown
of P4HA1 inhibited the synthesis of collagen IV, and hence disrupted the
structures of vascular basement membranes (BMs) in gliomas. Our study indicates
that P4HA1 plays a pivotal role in the process of GSC-EC transdifferentiation and
the structural formation of vascular BMs.
PMID- 28415788
TI - Inhibitory effects of BMP9 on breast cancer cells by regulating their interaction
with pre-adipocytes/adipocytes.
AB - Bone morphogenetic protein 9 (BMP9) possesses multiple functions, but its effects
on breast cancer cells in adipose microenvironment are still unclear. This study
aimed to investigate whether BMP9 is able to modulate the interaction between pre
adipocytes/adipocytes and breast cancer cells. An in vitro co-culture system was
established by using pre-adipocytes/adipocytes and MDA-MB-231 breast cancer cells
with BMP9 over-expression. The leptin expression and leptin-induced signaling
pathway were evaluated in this co-culture system. MTT assay, EdU assay and flow
cytometry were used to assess the proliferation of MDA-MB-231 cells. Wound
healing assay and Transwell migration assay were used to assess the migration of
MDA-MB-231 cells. Immunofluorescence staining was used to detect the expression
of leptin recepter (ObR) in MDA-MB-231 cells. The expression of key molecules in
leptin signaling pathway in co-culture system were detected by Western blotting.
MDA-MB-231 cells and pre-adipocytes/adipocytes were inoculated into nude mice,
the tumor volume was measured, and the protein expression of key molecules in
leptin signaling pathway was detected. Results showed BMP9 inhibited breast tumor
growth in vitro and in vivo and reduced the migration of breast cancer cells in
vitro. MDA-MB-231 cells with BMP9 over-expression decreased leptin expression in
pre-adipocytes/adipocytes and had reduced phosphorylation of STAT3, ERK1/2 and
AKT. Taken together, our study indicates that BMP9 can inhibit the growth and
metastasis of breast cancer cells, which may be related to interaction between
pre-adipocytes/adipocytes and MDA-MB-231 cells via leptin signaling pathway.
PMID- 28415789
TI - Hmga2 translocation induced in skin tumorigenesis.
AB - Hmga2 protein, a transcription factor involved in chromatin architecture, is
expressed chiefly during development, where it has many key biological functions.
When expressed in adult tissues from in various organs, Hmga2 is always related
to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not
yet understood. We demonstrated that Hmga2 can be found in non-transformed
epidermis, specifically located to the membrane of keratinocytes (KCs) in
epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and
TPA mouse models was associated with translocation of the Hmga2 protein from the
membrane into the nucleus, where Hmga2 induced its own expression by binding to
the Hmga2 promoter. Panobinostat, an HDAC inhibitor, downregulated Hmga2
expression by preventing Hmga2 to bind its own promoter, and thus inhibiting
Hmga2 promoter activity. Hmga2 translocation to the nucleus could in part be
prevented by an inhibitor for ROCK1. Our findings demonstrate that upon program
of benign papilloma to malignant cSCC of skin tumorigenesis, Hmga2 translocates
in a ROCK-dependent manner from the membrane to the nucleus, where it serves as
an autoregulatory transcription factor, causing cell transformation.
PMID- 28415790
TI - Hyperglycemia via activation of thromboxane A2 receptor impairs the integrity and
function of blood-brain barrier in microvascular endothelial cells.
AB - Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases,
including stroke, atherosclerosis and hypertension. This study was conducted to
elucidate whether and how thromboxane receptor (TPr) activation contributes to
blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular
endothelial cells (HBMECs) were cultured. The levels of phosphorylated
endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p
Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG)
or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt.
These effects were abolished by pharmacological or genetic inhibitors of TPr.
HG/U46619-induced suppressions of eNOS and Akt phosphorylation were accompanied
by upregulation of PTEN and Ser380/Thr382/383 PTEN phosphorylation. PTEN-specific
siRNA restored Akt-eNOS signaling in the face of TPr activation or HG. The small
GTPase, Rho, was also activated by HG stimulation, and pretreatment of HBMECs
with Y27632, a Rho-associated kinase (ROCK) inhibitor, rescued HG-impaired Akt
eNOS signaling. In STZ-injected rats, we found that hyperglycemia dramatically
increased the levels of PTEN and PTEN-Ser380/Thr382/383 phosphorylation, reduced
both levels of p-eNOS and p-Akt, and disrupted BBB function assayed by Evans blue
staining, which were abolished by SQ29548 treatment. We conclude that
hyperglycemia activates thromboxane A2 receptor to impair the integrity and
function of blood-brain barrier via the ROCK-PTEN-Akt-eNOS pathway.
PMID- 28415791
TI - Evaluation of the circulating level of fibroblast activation protein alpha for
diagnosis of esophageal squamous cell carcinoma.
AB - To evaluate whether circulating fibroblast activation protein alpha (FAPalpha)
could serve as a biomarker for the diagnosis of esophageal squamous cell
carcinoma (ESCC), enzyme-linked immunosorbent assay (ELISA) was used to detect
plasma FAPalpha in 556 participants including ESCC group, benign esophageal
disease group, healthy controls and other cancer controls group. The levels of
plasma FAPalpha were significantly decreased in ESCC patients (P < 0.001) and
showed a positive correlation with HDL-C levels (R = 0.372, P < 0.001). The
sensitivity and specificity of plasma FAPalpha were 56.1% and 85.6% based on the
optimal cut-off (49.04 ng/ml, AUC = 0.714). The combination of FAPalpha and the
traditional biomarkers (CEA, CYFR211 and SCCA) improved the sensitivity (41.5%)
without compromising the specificity (95.0%). Contradictorily, the
immunohistochemical staining revealed the overexpression of FAPalpha in stroma of
ESCC tissues. So the source of soluble FAPalpha was further explored by qRT-PCR,
Western blotting, ELISA and immunoprecipitation in fibroblast cell lines and
mouse xenograft models. We found that the plasma FAPalpha was not correlated with
the FAPalpha expressed in tumor, and the multi-organ might contribute to the
circulating levels of FAPalpha including skeletal muscle, liver and bone marrow.
These results indicated that the low plasma FAPalpha level might due to the
systemic reaction to the presence of tumor and circulating FAPalpha level might
be a potential indicator for diagnosing ESCC.
PMID- 28415792
TI - A CD44-specific peptide, RP-1, exhibits capacities of assisting diagnosis and
predicting prognosis of gastric cancer.
AB - Early diagnosis and evaluation of prognosis are both crucial for preventing poor
prognosis of patients with gastric cancer (GC), a leading cause of cancer-related
deaths worldwide. Cluster of differentiation 44 (CD44), an indicator of cancer
stem cells, can be specifically targeted by molecular probes and detected in
tissues of GC in a large quantity. In current study we found that RP-1, a
specific peptide binding to CD44 protein, exhibited the potentials of specific
binding to CD44 high-expressing cancer cells both in vitro and in vivo, and the
capacity of predicting prognosis of human GC in a microarray assay. Results
showed that RP-1 was characterized by high affinity, sensitivity and specificity,
and low toxicity, suggesting RP-1 could be an ideal bio-probe for accessory
diagnosis of GC. Further immunohistochemical studies and statistical analysis of
tissue microarray of human GC demonstrated similar sensitivity and specificity of
RP-1 with the monoclonal anti-CD44 antibody in the diagnosis of GC, and even
proved that positive RP-1 could be an independent risk factor. Therefore, this
study suggests RP-1 has the potentials of binding to CD44 protein expressed on
the membrane of GC cells, and demonstrates the feasibility and reliability of its
further application in molecular diagnosis and prognostic prediction of GC.
PMID- 28415793
TI - Clinical framework for next generation sequencing based analysis of treatment
predictive mutations and multiplexed gene fusion detection in non-small cell lung
cancer.
AB - Precision medicine requires accurate multi-gene clinical diagnostics. We describe
the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic
framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1
gene fusion assay for combined analysis of treatment predictive alterations in
non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden
(Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot
mutation concordance), after which 533 consecutive NSCLCs were collected during
one-year of routine clinical analysis in the healthcare region (~90% advanced
stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the
533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected
variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135
successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH
fusion positive case was missed by the NanoString assay. Stratification of the
533-sample cohort based on actionable alterations in 11 oncogenes revealed that
66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not
otherwise specified harbored >=1 alteration. In adenocarcinoma, 10.6% of patients
(50.3% if including KRAS) could potentially be eligible for emerging
therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or
ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1%
with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are
feasible in NSCLC for clinical diagnostics, identifying notable proportions of
patients potentially eligible for emerging molecular therapeutics.
PMID- 28415794
TI - MicroRNAs of the mir-17~92 cluster regulate multiple aspects of pancreatic tumor
development and progression.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by
resistance to currently employed chemotherapeutic approaches. Members of the mir
17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise
roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse
models, we show that loss of mir-17~92 reduces ERK pathway activation downstream
of mutant KRAS and promotes the regression of KRASG12D-driven precursor
pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal
exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and
Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that
lacked distant metastasis. Moreover, mir-17~92-deficient PDAC cell lines display
reduced invasion activity in transwell assays, form fewer invadopodia rosettes
than mir-17~92-competent cell lines and are less able to degrade extracellular
matrix. Specific inhibition of miR-19 family miRNAs with antagomirs recapitulates
these phenotypes, suggesting that miR-19 family miRNAs are important mediators of
PDAC cell invasion. Together these data demonstrate an oncogenic role for mir
17~92 at multiple stages of pancreatic tumorigenesis and progression;
specifically, they link this miRNA cluster to ERK pathway activation and
precursor lesion maintenance in vivo and identify a novel role for miR-19 family
miRNAs in promoting cancer cell invasion.
PMID- 28415795
TI - Renal sympathetic denervation guided by renal nerve stimulation to treat
ventricular arrhythmia in CKD patients with ICD.
AB - Chronic kidney disease (CKD) patients on stage 4 present greater risk rates for
malignant ventricular arrhythmia events. This study examined patients with CKD in
stages 1, 2, 3 and 4, left ventricular dysfunction and automatic implantable
cardioverter-defibrillator (ICD). Our goal was to record the appropriate
therapies, "Anti-tachycardia Therapy Pacing" (ATP) and shock events during the 18
months of follow-up and compare the incidence and severity of these at different
stages of CKD, mainly in patients with CKD stage 4 underwent renal sympathetic
denervation (RSD) guided by renal nerve stimulation (RNS). One hundred and
fifteen patients were evaluated once every three months till 18 months of follow
up. The arrhythmic events were assessed at each follow-up visit. Comparing the
groups, we can see the number of ATP and shock events recorded by ICD during 18
months of follow-up, and differences in the number of therapeutic events between
the various stages of CKD. The hazard ratio (HR), 95% confidence interval (CI)
and P value for ATP and shock events between all the CKD stages were evaluated by
the log-rank/Mantel-Haenszel test. At the 18th month of follow-up, 75% of
patients with CKD stage 4 received ATP, and 70% were treated with shock while
only 20% of the subjects with CKD stage 4 that were submitted to RSD received ATP
and 20% were treated with shock, P<0.0001 and P=0.0002, respectively. In our
study, a decline occurred in the incidence of arrhythmias, and therefore,
appropriate ICD therapies in advanced stages of CKD, reducing the risk rates for
these events in patients with CKD on stage 4 after RSD guided by RNS in
comparison to the other CKD stages. Our results suggest that RSD can control the
higher incidence of malignant arrhythmias in advanced CKD stages.
PMID- 28415796
TI - Macrophage-stimulated microRNA expression in mural cells promotes transplantation
induced neointima formation.
AB - In this study, we tested the possibility that macrophages might contribute to
neointima formation by stimulating microRNA expressions in mural cells. Thoracic
aortas from F344 rats were transplanted into recipient Lewis rats. Clodronate
liposome was used for in vivo macrophage depletion. Using miR-21 as a prototypic
example of vascular enriched microRNA, we showed that macrophage depletion
reduced the expression level of miR-21, which was upregulated in the allograft.
This effect of macrophage depletion was accompanied by attenuations in neointimal
hyperplasia and transplantation-induced vascular inflammation. Using in vitro
assays, we identified that macrophages might stimulate miR-21 expression in
smooth muscle cells and adventitial fibroblasts via the release of tumor necrosis
factor-alpha. We also showed that silencing of miR-21 suppressed tumor necrosis
factor-induced proliferation, migration, and inflammatory responses in mural
cells. Our results suggest that macrophage may promote transplantation-induced
neointima formation by stimulating miR-21 expression in vascular mural cells,
which promotes mural cell proliferation, migration and/or inflammation. Moreover,
we have established that tumor necrosis factor-alpha has a major role in
mediating this paracrine process.
PMID- 28415797
TI - Rab7 GTPase controls lipid metabolic signaling in myeloid-derived suppressor
cells.
AB - Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that
regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs)
through over-activation of mammalian target of rapamycin (mTOR). Affymetrix
GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed
upregulation of Rab7 GTPase protein, which belongs to a superfamily of small
molecular-weight GTPase known to regulate intracellular membrane trafficking from
early to late endosomes and lysosomes. Here, the physical protein-protein
interaction between Rab7 GTPase and mTOR has been detected by co
immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like
HD1B myeloid cell lines. The GST pull down assay using the recombinant GST-Rab7
GTPase fusion protein showed that Rab7 GTPase interacts with the mTOR N-terminal
heat repeat domain. Rab7 GTPase siRNA knocking down reversed the altered
lysosome/mTOR distribution and expression levels in HD1B cells. Rab7 GTPase siRNA
knocking down in isolated bone marrow lal-/- MDSCs or HD1B cells not only reduced
over-activation of mTOR and its downstream effector S6, but also decreased
glucose consumption, decreased ROS over-production, and increased healthy
mitochondria by membrane potential measurement. Inhibition of Rab7 GTPase led to
reduced lal-/- MDSCs differentiation from bone marrow Lin- progenitor cells,
reduced lal-/- MDSCs trans-endothelial migration, and reversed lal-/- MDSCs
suppression of T cell proliferation. Furthermore, inhibition of Rab7 GTPase
reduced lal-/- MDSCs ability to stimulate tumor cell proliferation in vitro,
tumor growth in vivo, and tumor invasion. Together, these results showed that
Rab7 GTPase is critically involved in MDSCs homeostasis and pathogenic functions.
PMID- 28415798
TI - Tumor-derived IL-18 induces PD-1 expression on immunosuppressive NK cells in
triple-negative breast cancer.
AB - PURPOSE: While the inflammatory cytokine interleukin-18 (IL-18) is known to
activate natural killer (NK) cells, its precise role in cancer is controversial.
In this study, we investigated the role of tumor-derived IL-18 on peripheral
blood NK cells in breast cancer patients. RESULTS: In breast cancer cell lines,
IL-18 was expressed and secreted in the triple-negative breast cancer (TNBC) cell
lines MDA-MB-231 and HCC-70 but not in MCF-7 cells. The immature and non
cytotoxic CD56dimCD16dim/- NK cell fraction was increased following co-culture
with MDA-MB-231 cells, and this increase was not observed with tumor cells
transfected with siRNA for IL-18 or in MCF-7 cells. In addition, tumor-derived IL
18 increased PD-1 expression on CD56dimCD16dim/- NK cells, although no effect on
PD-L1 expression in tumor cells was observed. Among EBC patients, serum IL-18
levels were significantly increased in those with a TNBC subtype compared to
levels from patients with other subtypes, and the IL-18 levels were strongly
associated with poor survival. Similarly, serum IL-18 and CD56dimCD16dim/- NK
cells were also increased in patients with metastatic TNBC who had progressive
disease following cytotoxic chemotherapy. EXPERIMENTAL DESIGN: We performed in
vitro experiments in breast cancer cell lines, measured cytokine levels by RT
qPCR, western blot, and ELISA, and analyzed NK cell subsets by flow cytometry.
For clinical validation, we collected and analyzed blood sample from patients
with early breast cancer (EBC, N = 545) and metastatic breast cancer (MBC, N =
42). CONCLUSIONS: Our data revealed that tumor-derived IL-18 is associated with
bad prognosis in patients with TNBC. Tumor-derived IL-18 increased the
immunosuppressive CD56dimCD16dim/- NK cell fraction and induced PD-1 expression
on these NK cells.
PMID- 28415799
TI - The pancreas responds to remote damage and systemic stress by secretion of the
pancreatic secretory proteins PSP/regI and PAP/regIII.
AB - INTRODUCTION: In patients with infection and sepsis serum levels of Pancreatic
Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP
during these conditions is presumably the pancreas, however, an intestinal origin
cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was
identified in the pancreas. These proteins were also localized in intestinal
organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal
models of sepsis and in healthy humans. RESULTS: PSP and PAP responded to remote
lesions in rats although the pancreatic response was much more pronounced than
the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content
in the pancreas compared to any other organ while PAP was most abundant in the
small intestine. Both proteins responded to CLP or sham operation in the
pancreas. PSP also increased in the intestine during CLP. The distribution of PSP
and PAP in human tissue mirrored the distribution in the murine models. MATERIALS
AND METHODS: Distribution of PSP and PAP was visualized by immunohistochemistry.
Rats and mice underwent midline laparotomies followed by mobilization of tissue
and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture
(CLP) procedures or sham laparotomies were performed. Human tissue extracts were
analyzed for PSP and PAP. CONCLUSIONS: The pancreas reacts to remote lesions and
septic insults in mice and rats with increased PSP synthesis, while PAP is
selectively responsive to septic events. Furthermore, our results suggest that
serum PSP in septic patients is predominantly derived through an acute phase
response of the pancreas.
PMID- 28415800
TI - Selenophosphate synthetase 1 (SPS1) is required for the development and selenium
homeostasis of central nervous system in chicken (Gallus gallus).
AB - Selenophosphate synthetase (SPS) is essential for selenoprotein biosynthesis. In
two SPS paralogues, SPS1 was only cloned from a cDNA library prepared from avian
organ. However, the biological function of SPS1 in chicken central nervous system
(CNS) remains largely unclear. To investigate the role of avian SPS1 in the
development and selenium (Se) homeostasis of CNS, fertile eggs, chicken embryos,
embryo neurons and chicks were employed in this study. The response of SPS1
transcription to the development and Se levels of CNS tissues was analyzed using
qRT-PCR. SPS1 gene exists extensively in the development of chicken CNS. The wide
expression of avian SPS1 can be controlled by the Se content levels, which
suggests that SPS1 is important in the regulation of Se homeostasis. The
fundamental mechanism of these effects is that Se alters the half-life and
stability of SPS1 mRNA. Therefore, SPS1 exerts an irreplaceable biological
function in chicken CNS and Se homeostasis is closely related to the expression
of SPS1. These results suggested that SPS1 was required for the development and
Se homeostasis of CNS in chicken.
PMID- 28415801
TI - Identification of long non-coding RNAs that stimulate cell survival in bladder
cancer.
AB - For many years, research on the biology underlying bladder cancer focused on
protein-coding genes which cover only about 3% of the human genome. Recently, it
was discovered that a large part of the human genome is actively transcribed as
long non-coding RNAs (lncRNAs). LncRNAs are master regulators of gene expression
and several lncRNAs were shown to play a role in bladder cancer development and
progression. Here, we analyzed lncRNA expression in muscle-invasive bladder
cancer (MIBC) using the MiTranscriptome database of cancer lncRNA expression
profiles, and we studied their function in bladder cancer-derived tumor cells.
Analysis of the MiTranscriptome lncRNA expression data revealed four MIBC
subgroups, which partially overlapped with the four mRNA clusters identified by
The Cancer Genome Atlas consortium. Up-regulation of three lncRNAs CAT266,
CAT1297, and CAT1647 in bladder cancer, in comparison to normal urothelium, was
confirmed in an independent series of normal, non-muscle invasive (NMIBC) and
MIBC tissue samples. Furthermore, expression levels of CAT1297 were found to be
correlated with disease-free and overall survival in MIBC. Knockdown of CAT266,
CAT1297, and CAT1647 decreased cell viability and colony formation, due to the
induction of apoptosis. In conclusion, our data show that lncRNAs expression is
de-regulated in MIBC and three aberrantly expressed transcripts regulate
proliferation and apoptosis. Our data indicate that lncRNAs play an important
role in MIBC development and progression and are a treasure chest for the
discovery of new biomarkers.
PMID- 28415806
TI - Lithium protects hippocampal progenitors, cognitive performance and hypothalamus
pituitary function after irradiation to the juvenile rat brain.
AB - Cranial radiotherapy in children typically causes delayed and progressive
cognitive dysfunction and there is no effective preventive strategy for radiation
induced cognitive impairments. Here we show that lithium treatment reduced
irradiation-induced progenitor cell death in the subgranular zone of the
hippocampus, and subsequently ameliorated irradiation-reduced neurogenesis and
astrogenesis in the juvenile rat brain. Irradiation-induced memory impairment,
motor hyperactivity and anxiety-like behaviour were normalized by lithium
treatment. Late-onset irradiation-induced hypopituitarism was prevented by
lithium treatment. Additionally, lithium appeared relatively toxic to multiple
cultured tumour cell lines, and did not improve viability of radiated DAOY cells
in vitro. In summary, our findings demonstrate that lithium can be safely
administered to prevent both short- and long-term injury to the juvenile brain
caused by ionizing radiation.
PMID- 28415808
TI - IKK inhibition by BMS-345541 suppresses breast tumorigenesis and metastases by
targeting GD2+ cancer stem cells.
AB - We have identified that the ganglioside GD2 is a marker for breast cancer stem
cells (BCSCs), and that targeting the enzyme GD3 synthase (GD3S, which regulates
GD2 biosynthesis) reduces breast tumorigenesis. The pathways regulating GD2
expression, and their anomalous functions in BCSC, are unclear. Proteomic
analysis of GD2+ and GD2- cells from breast cancer cell lines revealed the
activation of NFkappaB signaling in GD2+ cells. Dose- and time-dependent
suppression of NFkappaB signaling by the small molecule inhibitor BMS-345541
reduced GD2+ cells by > 90%. Likewise, BMS-345541 inhibited BCSC GD3S expression,
mammosphere formation, and cell migration/invasion in vitro. Breast tumor-bearing
mice treated with BMS-345541 showed a statistically significant decrease in tumor
volume and exhibited prolonged survival compared to control mice, with a median
survival of 78 d for the BMS-345541-treated group vs. 58 d for the controls.
Moreover, in an experimental metastases model, treatment with BMS-345541 reduced
the lung metastases by > 5-fold. These data suggest that GD2 expression and
function,and NFkappaB signaling, are related, and they control BCSCs tumorigenic
characteristics. Thus, the suppression of NFkappaB signaling by BMS-345541 is a
potentially important advance in controlling breast cancer growth and metastases.
PMID- 28415805
TI - Regulatory functional territory of PLK-1 and their substrates beyond mitosis.
AB - Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and
is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly
associated with poor prognosis and cancer progression, it is one of the most
extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell
cycle events, such as spindle pole maturation, chromosome segregation and
cytokinesis. However, studies have demonstrated that the role of PLK-1 is not
only restricted to mitosis, but PLK-1 can also regulate other vital events beyond
mitosis, including transcription, translation, ciliogenesis, checkpoint
adaptation and recovery, apoptosis, chromosomes dynamics etc. Recent reviews have
tried to define the regulatory role of PLK-1 during mitosis progression and
tumorigenesis, but its' functional role beyond mitosis is still largely
unexplored. PLK-1 can regulate the activity of many proteins that work outside of
its conventional territory. The dysregulation of these proteins can cause
diseases such as Alzheimer's disease, tumorigenesis etc. and may also lead to
drug resistance. Thus, in this review, we discussed the versatile role of PLK-1
and tried to collect data to validate its' functional role in cell cycle
regulation apart from mitosis.
PMID- 28415811
TI - IL-33/ST2-mediated inflammation in macrophages is directly abrogated by IL-10
during rheumatoid arthritis.
AB - IL-10 is an immunosuppressive cytokine produced and sensed by many immune cells
and exerts a protective role in autoimmune diseases. However, the underlying
mechanism by which IL-10 contributes to prevent the arthritic inflammation in
macrophages is poorly understood. Herein we report on a novel anti-arthritic
property of IL-10 through the inhibition of IL-33 signaling by macrophages during
collagen-induced arthritis (CIA) development. We show that IL-33 expression
rather than its receptor (ST2) is positively correlated with IL-10 level in
active RA. IL-10 deficiency in mice leads to significant upregulation of IL-33
expression and aggravates the progression of CIA, while exogenous IL-10 treatment
effectively diminishes IL-33 production in IL-10 knockout (IL-10-/-) CIA mice. We
demonstrate further that the inhibitory effect of IL-10 in suppressing IL-33
production requires STAT3 activation in macrophages. Furthermore, IL-33
stimulated proinflammatory genes are notably increased in IL-10-/- CIA mice,
whereas macrophages treated with recombinant IL-10 exhibit decreased IL-33
amplified inflammation and inhibited IL-33 activated NF-kappaB signaling pathway.
Our findings indicate that IL-10 act as a negative regulator of IL-33/ST2
signaling pathways in vivo, suggesting a potential therapeutic role of IL-10 in
autoimmune diseases.
PMID- 28415814
TI - Concurrent chemo-radiotherapy with S-1 as an alternative therapy for elderly
Chinese patients with non-metastatic esophageal squamous cancer: evidence based
on a systematic review and meta-analysis.
AB - OBJECTIVE: This systematic review and meta-analysis aims to systematically assess
the effects of concurrent chemo-radiotherapy (CRT) compared with radiotherapy
(RT) alone for elderly Chinese patients with non-metastatic esophageal squamous
cancer. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of
Controlled Trials (CENTRAL), China Biomedical Literature Database (CBM), and
China National Knowledge Infrastructure (CNKI) databases. We retrieved randomized
controlled trials on concurrent CRT with Gimeraciland Oteracil Porassium (S-1)
compared with RT alone for aged Chinese patients with non-metastatic esophageal
squamous cancer performed until August 2016. RESULTS: Eight eligible studies
involving 536 patients were subjected to meta-analysis. As a response rate
measure, a relative risk (RR) of 1.37 [95% confidence intervals (CIs): 1.24,
1.53; P = 0.00], which reached statistical significance, was estimated when
concurrent CRT with S-1 was performed compared with RT alone. Sensitivity
analysis on response rate confirmed the robustness of the pooled result. The RR
values of 1.44 (95% CIs: 1.22, 1.70; P = 0.00) and 1.77 (95% CIs: 1.26, 2.48; P =
0.00) estimated for 1- and 2-year survival rate indices, respectively, were also
statistically significant. The incidence of adverse events was similar in both
groups. CONCLUSION: This review concluded that concurrent CRT with S-1 can
improve the efficacy and prolong the survival period of elderly Chinese patients
with non-metastatic esophageal squamous cancer and does not significantly
increase the acute adverse effects of RT alone.
PMID- 28415812
TI - Signal transduction growth factors: the effective governance of transcription and
cellular adhesion in cancer invasion.
AB - Giulio Bizzozero classified the tissues concerning their capacity to self-renew
during the adult life in labile, stable and permanent tissues. In 1940 Viktor
Hamburger and Rita Levi Montalcini exposed the possibility to induce the growth
of permanent cells thanks to a specific ligand Nerve Growth Factor (NGF). Stanley
Cohen purified a protein the Epidermal Growth Factor (EGF), able to induce
epidermis proliferation and to elicit precocious eye disclosure and teeth
eruption, establishing the "inverse" relationships between the proliferation and
differentiation. These two biological effects induced by EGF were according to
EGFR signaling is involved in a large array of cellular functions such as
proliferation, survival, adhesion, migration and differentiation. This review is
focused on the key role of growth factors signaling and their downstream
effectors in physiological and in pathological phenomena, the authors highlight
the governance of Growth factors during the EMT in cancer invasion.
PMID- 28415815
TI - BI-RADS 3-5 microcalcifications: prediction of lymph node metastasis of breast
cancer.
AB - PURPOSE: To determine whether the clinicopathological parameters and Breast
Imaging Reporting and Data System (BI-RADS) 3-5 microcalcifications differed
between lymph node positive (LN (+)) and lymph node negative (LN (-)) invasive
ductal carcinoma (IDC). RESULTS: For microcalcification-associated breast
cancers, seven selected features (age, tumor size, Ki-67 status, lymphovascular
invasion, calcification range, calcification diameter and calcification density)
were significantly associated with LN status (all P < 0.05). Multivariate
logistic regression analysis found that three risk factors (age: older vs.
younger OR: 0.973 P = 0.006, tumor size: larger vs. smaller OR: 1.671, P < 0.001
and calcification density: calcifications > 20/cm2 vs. calcifications <= 20/cm2
OR: 1.698, P < 0.001) were significant independent predictors. This model had an
area under the receiver operating characteristic curve (AUC) of 0.701. The nodal
staging (N0 and N1 chi2 = 5.701, P = 0.017; N0 and N2 chi2 = 6.614, P = 0.013)
was significantly positively associated with calcification density. The luminal B
subtype had the highest risk of LN metastasis. Multivariate analysis demonstrated
that calcification > 2 cm in range (OR: 2.209) and larger tumor size (OR: 1.882)
were independently predictive of LN metastasis in the luminal B subtype (AUC =
0.667). MATERIALS AND METHODS: Mammographic images of 419 female breast cancer
patients were included. Associations between the risk factors and LN status were
evaluated using a Chi-square test, ANOVA and binary logistic regression analysis.
CONCLUSIONS: This study found that age, tumor size and calcifications density can
be conveniently used to facilitate the preoperative prediction of LN metastasis.
The luminal B subtype has the highest risk of LN metastasis among the
microcalcification-associated breast cancers.
PMID- 28415816
TI - Targeting the PIM protein kinases for the treatment of a T-cell acute
lymphoblastic leukemia subset.
AB - New approaches are needed for the treatment of patients with T-cell acute
lymphoblastic leukemia (T-ALL) who fail to achieve remission with chemotherapy.
Analysis of the effects of pan-PIM protein kinase inhibitors on human T-ALL cell
lines demonstrated that the sensitive cell lines expressed higher PIM1 protein
kinase levels, whereas T-ALL cell lines with NOTCH mutations tended to have lower
levels of PIM1 kinase and were insensitive to these inhibitors. NOTCH-mutant
cells selected for resistance to gamma secretase inhibitors developed elevated
PIM1 kinase levels and increased sensitivity to PIM inhibitors. Gene profiling
using a publically available T-ALL dataset demonstrated overexpression of PIM1 in
the majority of early T-cell precursor (ETP)-ALLs and a small subset of non-ETP
ALL. While the PIM inhibitors blocked growth, they also stimulated ERK and STAT5
phosphorylation, demonstrating that activation of additional signaling pathways
occurs with PIM inhibitor treatment. To block these pathways, Ponatinib, a
broadly active tyrosine kinase inhibitor (TKI) used to treat chronic myelogenous
leukemia, was added to this PIM-inhibitor regimen. The combination of Ponatinib
with a PIM inhibitor resulted in synergistic T-ALL growth inhibition and marked
apoptotic cell death. Treatment of mice engrafted with human T-ALL with these two
agents significantly decreased the tumor burden and improved the survival of
treated mice. This dual therapy has the potential to be developed as a novel
approach to treat T-ALL with high PIM expression.
PMID- 28415817
TI - An updated meta-analysis of 23 case-control studies on the association between
miR-34b/c polymorphism and cancer risk.
AB - The association between in microRNA-34b/c gene rs4938723 polymorphisms and cancer
risk remains inconclusive. This meta-analysis was performed to analyze the
association between microRNA-34b/c rs4938723 polymorphism and risk for cancer
development. In total, 304 studies from PubMed, Embase, Web of Science, Wanfang,
and Chinese National Knowledge Infrastructure databases were examined, and 23
studies were included in this meta-analysis. The 23 selected studies involved
10,812 cancer cases and 11,719 controls. Odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated to measure the strength of the association. Our
results indicate a significant association between the rs4938723 polymorphism and
cancer risk in the overdominant model (P heterogeneity = 0.018, OR = 1.093, and
95% CI = 1.015-1.177 for CT vs. CC/TT). Using a stratified subgroup analysis,
rs4938723 polymorphisms were associated with an increased risk for hepatocellular
carcinoma, but decreased risk for colorectal, gastric, and esophageal squamous
cell cancer. These findings indicate that the rs4938723 gene is a susceptible
locus for cancer.
PMID- 28415818
TI - Mechanistic characterization of a copper containing thiosemicarbazone with potent
antitumor activity.
AB - BACKGROUND: The thiosemicarbazone CD 02750 (VLX50) was recently reported as a hit
compound in a phenotype-based drug screen in primary cultures of patient tumor
cells. We synthesized a copper complex of VLX50, denoted VLX60, and characterized
its antitumor and mechanistic properties. MATERIALS AND METHODS: The cytotoxic
effects and mechanistic properties of VLX60 were investigated in monolayer
cultures of multiple human cell lines, in tumor cells from patients, in a 3-D
spheroid cell culture system and in vivo and were compared with those of VLX50.
RESULTS: VLX60 showed >= 3-fold higher cytotoxic activity than VLX50 in 2-D
cultures and, in contrast to VLX50, retained its activity in the presence of
additional iron. VLX60 was effective against non-proliferative spheroids and
against tumor xenografts in vivo in a murine model. In contrast to VLX50, gene
expression analysis demonstrated that genes associated with oxidative stress were
considerably enriched in cells exposed to VLX60 as was induction of reactive
oxygen. VLX60 compromised the ubiquitin-proteasome system and was more active in
BRAF mutated versus BRAF wild-type colon cancer cells. CONCLUSIONS: The cytotoxic
effects of the copper thiosemicarbazone VLX60 differ from those of VLX50 and
shows interesting features as a potential antitumor drug, notably against BRAF
mutated colorectal cancer.
PMID- 28415819
TI - Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen
resistance in estrogen receptor-positive breast cancer cells.
AB - Tamoxifen is still the most commonly used endocrine therapy drug for estrogen
receptor (ER)-positive breast cancer patients and has an excellent outcome, but
tamoxifen resistance remains a great impediment to successful treatment. Recent
studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that
aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF
7, especially when combined with tamoxifen, but also has a potential function to
overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can
down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen
alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line
but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the
expression of these proteins in the resistant cell line. When knocking down c-myc
in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as
well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to
overcome tamoxifen resistance. Our study discovered a novel role of aspirin based
on its anti-tumor effect, and put forward some kinds of possible mechanisms of
tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy
for the treatment of ER-positive breast carcinoma.
PMID- 28415820
TI - Targeting programmed cell death ligand 1 by CRISPR/Cas9 in osteosarcoma cells.
AB - Programmed cell death ligand 1 (PD-L1) is a transmembrane protein that is
expressed on tumor cells that suppresses the T cell-mediated immune response.
Therapies targeting the PD-L1 pathway promote anti-tumor immunity and have shown
promising results in some types of cancers. However, the functional and
therapeutic roles of PD-L1 in osteosarcoma remain largely unknown. In this study,
we found that PD-L1 protein was expressed in osteosarcoma cell lines and tissue
microarray of patient tumors. Tissue microarray immunohistochemistry analysis
showed that the overall and five-year survival rates of patients with high levels
of PD-L1 expression were significantly shorter than patients with low levels.
High levels of PD-L1 expression were also associated with metastasis in
osteosarcoma patients. Furthermore, we applied the Clustered Regularly
Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to target PD-L1 gene
at the DNA level in osteosarcoma cell lines. We found that the expression of PD
L1 could be efficiently disrupted by CRISPR/Cas9 system and PD-L1 knockdown
increased drug sensitivities for doxorubicin and paclitaxel. These results
suggest that PD-L1 is an independent prognostic factor in osteosarcoma and that
PD-L1 knockout by CRISPR/Cas9 may be a therapeutic approach for the treatment of
osteosarcoma.
PMID- 28415821
TI - Deep sequencing-based microRNA expression signatures in head and neck squamous
cell carcinoma: dual strands of pre-miR-150 as antitumor miRNAs.
AB - We adopted into RNA-sequencing technologies to construct the microRNA (miRNA)
expression signature of head and neck squamous cell carcinoma (HNSCC). Our
signature revealed that a total of 160 miRNAs (44 upregulated and 116
downregulated) were aberrantly expressed in cancer tissues. Expression of miR-150
5p (guide strand miRNA) and miR-150-3p (passenger strand miRNA) were
significantly silenced in cancer tissues, suggesting both miRNAs act as antitumor
miRNAs in HNSCC cells. Ectopic expression of mature miRNAs, miR-150-5p and miR
150-3p inhibited cancer cell aggressiveness. Low expression of miR-150-5p and miR
150-3p predicted significantly shorter overall survival in patients with HNSCC (P
= 0.0091 and P = 0.0386) by Kaplan-Meier survival curves analyses. We identified
that integrin alpha3 (ITGA3), integrin alpha6 (ITGA6), and tenascin C (TNC) were
coordinately regulated by these miRNAs in HNSCC cells. Knockdown assays using
siRNAs showed that ITGA3, ITGA6 and TNC acted as cancer promoting genes in HNSCC
cells. Moreover, ITGA3, ITGA6, and TNC alterations were associated with
significantly poorer overall survival (P = 0.0177, P = 0.0237, and P = 0.026,
respectively). Dual strands of pre-150 (miR-150-5p and miR-150-3p) functioned as
antitumor miRNAs based on the miRNA expression signature of HNSCC. Identification
of antitumor miR-150-mediated RNA networks may provide novel insights into
pathogenesis of HNSCC.
PMID- 28415822
TI - Interaction between granulin A and enolase 1 attenuates the migration and
invasion of human hepatoma cells.
AB - Granulin A (GRN A), a peptide with a molecular 6 kDa, is derived from proteolysis
of progranulin (PGRN). Previous study in our laboratory has shown that GRN A is
able to inhibit cancer cell growth significantly. In the present study, we
confirmed that GRN A can bind to alpha-enolase (ENO1) specifically as analyzed
using Pull-down/MS approaches. The interaction of GRN A with ENO1 was further
confirmed by Western blotting and Surface plasmon resonance (SPR) analysis.
Treatment of human HepG-2 cells with GRN A inhibited cancer cell growth as well
as migration and invasion of cancer cells as analyzed by the 3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) and Scratch wound
healing assay as well as Transwell experiments. Additionally, GRN A treatment
results in augmentation of glucose uptake in cancer cells. Further study reveals
that higher expression of ENO1 reversed the inhibitory effects of GRN A on
migration and invasion of HepG-2 cells. The increase of glucose uptake, as well
as the expression of apoptosis-related genes, is also reversed in cells
overexpressing ENO1. The study provides solid evidence that there is the
interaction between GRN A and ENO1 and the interaction is responsible for the
effects of GRN A on glucose uptake as well as cancer cell migration and invasion.
PMID- 28415823
TI - Recurrent fusion RNA DUS4L-BCAP29 in non-cancer human tissues and cells.
AB - Traditional gene fusions are involved in the development of various neoplasia.
DUS4L-BCAP29, a chimeric fusion RNA, has been reported to be a cancer-fusion in
prostate and gastric cancer, in addition to playing a tumorigenic role. Here, we
showed that the DUS4L-BCAP29 fusion transcript exists in a variety of normal
tissues. It is also present in non-cancer epithelial, as well as in fibroblast
cell lines. Quantitatively, the fusion transcript has a comparable expression in
non-cancerous, gastric and prostate cell lines and tissues as in the cancer cell
lines and tissues. The loss-of-function approach as previously reported is not
sufficient to prove the functionality of the fusion. On the other hand, the gain
of-function approach showed that overexpression of DUS4L-BCAP29 promotes cell
growth and motility, even in non-cancer cells. Finally, we provide further
evidence that the fusion transcript is a product of cis-splicing between adjacent
genes. In summary, we believe that in contrast to traditional gene fusions, DUS4L
BCAP29 cannot be used as a cancer biomarker. Instead, it is a fusion transcript
that exists in normal physiology and that its pro-growth effect is not unique to
cancer cells.
PMID- 28415824
TI - Influence of marital status on the survival of adults with
extrahepatic/intrahepatic cholangiocarcinoma.
AB - Although the prognostic value of marital status has been implicated in many
cancers, its prognostic impact on cholangiocarcinoma has not yet been determined.
The aim of this study was to examine the association between marital status and
cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma
cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from
the Surveillance, Epidemiology, and End Results database. We found widowed
patients were more likely to be female, aged more than 70, and from low income
areas. Multivariate analysis indicated that marital status was an independent
prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis
suggested the widowed status independently predicted poor survival at regional
stage and in older patients with intrahepatic cholangiocarcinoma. To conclude,
marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed
patients are at greater risk of death than others.
PMID- 28415825
TI - Recombinant human erythropoietin stimulates melanoma tumor growth through
activation of initiation factor eIF4E.
AB - Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer
patients. Recent clinical trials suggest that EPO may accelerate tumor
progression and increase mortality. However, the evidence supporting a growth
promoting effect of EPO has remained controversial. Employing an in vivo model of
B16 murine melanoma, we observed that administration of EPO to tumor bearing
C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro
studies demonstrate that B16 murine melanoma cells express EPOR, both at the
protein and mRNA levels. Interestingly, expression of EPOR was retained in the
established tumors. EPO stimulation of B16 cells enhanced proliferation and
protein synthesis rates, and correlated with activation of the receptor
associated Janus kinase 2 (Jak2) as well as phosphorylation of extracellular
signal-regulated kinase (Erk) 1/2 and Akt kinases. Treatment with EPO and Jak-2
antagonists significantly inhibited EPO-mediated B16 cell proliferation.
Moreover, EPO dose-dependently induced the phosphorylation and activation of the
translation initiation factor eIF4E as well as the phosphorylation of its
repressor, the eIF4E binding protein 4E-BP1. Finally, using eIF4E small
interfering RNA (siRNA), we observed that EPO-mediated stimulation of B16 cell
proliferation is eIF4E-dependent. Our results indicate that EPO exerts a powerful
stimulatory effect on cell proliferation and de novo protein synthesis in
melanoma cells through activation of the initiation factor eIF4E.
PMID- 28415826
TI - Azithromycin augments rhinovirus-induced IFNbeta via cytosolic MDA5 in
experimental models of asthma exacerbation.
AB - Deficient production of anti-viral interferons (IFNs) may be involved in causing
viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production
would be warranted. Azithromycin may reduce asthma exacerbations but its modus
operandi is unknown. Here, we investigated if azithromycin induces IFNbeta
expression in vitro in rhinovirus-infected bronchial epithelial cells from
asthmatic donors and in vivo in our allergic inflammation-based mouse model of
viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently
augmented viral-induced IFNbeta expression in asthmatic, but not in healthy
bronchial epithelial cells. The effect negatively correlated with viral load.
Knockdown of MDA5 and RIG-I by siRNA showed involvement of MDA5 but not RIG-I in
azithromycin's IFN-inducing effects in vitro. In vivo azithromycin induced
IFNbeta protein, restoring a reduced lung IFN response exclusively in allergic
exacerbating mice. This was associated with induction of interferon-stimulated
genes and MDA5, but not RIG-I. We suggest that clinically relevant concentrations
of azithromycin produce MDA5-dependent, anti-viral, IFN-inducing effects in
bronchial epithelium distinctly from asthmatic donors. Similarly, azithromycin
induced MDA5-associated IFN in virally stimulated lungs in vivo exclusively in
allergic mice. Effects of azithromycin and MDA5-active drugs on viral-induced
exacerbations deserve further research.
PMID- 28415827
TI - Camptothecin resistance is determined by the regulation of topoisomerase I
degradation mediated by ubiquitin proteasome pathway.
AB - Proteasomal degradation of topoisomerase I (topoI) is one of the most remarkable
cellular phenomena observed in response to camptothecin (CPT). Importantly, the
rate of topoI degradation is linked to CPT resistance. Formation of the topoI-DNA
CPT cleavable complex inhibits DNA re-ligation resulting in DNA-double strand
break (DSB). The degradation of topoI marks the first step in the ubiquitin
proteasome pathway (UPP) dependent DNA damage response (DDR). Here, we show that
the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein
kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is
subsequently ubiquitinated by BRCA1. A higher basal level of topoI-pS10 ensures
rapid topoI degradation leading to CPT resistance. Importantly, PTEN regulates
DNA-PKcs kinase activity in this pathway and PTEN deletion ensures DNA-PKcs
dependent higher topoI-pS10, rapid topoI degradation and CPT resistance.
PMID- 28415830
TI - Triptolide mitigates radiation-induced pneumonitis via inhibition of alveolar
macrophages and related inflammatory molecules.
AB - Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy
for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate
IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the
underlying mechanism by which TPL mitigates the effects of radiotoxicity. The
results showed that:(1) Alveolar macrophages (AMs) were the primary inflammatory
cells infiltrating irradiated lung tissues and were maintained at a high level
for at least 17 days, which TPL could reduce by inhibiting of the production of
macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2.(2) Stimulated
by the co-cultured irradiated lung epithelium, AMs produced a panel of
inflammative molecules (IMs), such as cytokines (TNF-alpha, IL-6, IL-1alpha, IL
1beta) and chemokines (MIP-2, MCP-1, LIX). TPL-treated AMs could reduce the
production of these IMs. Meanwhile, AMs isolated from irradiated lung tissue
secreted significantly high levels of IMs, which could be dramatically reduced by
TPL.(3) TPL suppressed the phagocytosis of AMs as well as ROS production.Our
results indicate that TPL mitigates radiation-induced pulmonary inflammation
through the inhibition of the infiltration, IM secretion, and phagocytosis of
AMs.
PMID- 28415833
TI - Molecular Characterization and Biodiversity of a Putative Chlorotoxin from the
Iranian Yellow Scorpion Odontobuthus doriae
AB - BAckground: Chloride channels have already been over-expressed in the different
types of cancer. Chlorotoxins, as the blocking agent of these channels, have been
indicated to be an effective drug against tumors. In this study, we characterized
a putative chlorotoxin from a cDNA library of the venom glands obtained from the
Iranian scorpion Odontobuthus doriae. Methods: A cDNA library was constructed
from venom gland transcriptome of six scorpions. The cDNA encoding Odontobuthus
doriae chlorotoxin was isolated from the library, and its putative peptide was
characterized by some bioinformatics software such as protein blast, SignalP4.0,
DISULFIND and Clustal Omega. Results: The mature Odontobuthus doriae chlorotoxin
peptide has a 35-amino-acid residue and four disulfide bounds. This putative
chlorotoxin is a small, compact, and stable molecule. Moreover, based on the open
reading frame sequence similarity, this peptide is similar to Buthus martensii
Karsch chlorotoxin like toxin and Bm12-b neurotoxins from the Chinese scorpion
Mesobuthus martensii. Conclusion: The small size of this putative chlorotoxin and
its stability make it as a suitable candidate for medical and pharmacological
research, especially in the cancer research.
PMID- 28415831
TI - Definitive radiochemotherapy versus surgery within multimodality treatment in
stage III non-small cell lung cancer (NSCLC) - a cumulative meta-analysis of the
randomized evidence.
AB - Randomized trials were analyzed comparing surgery with definitive radiotherapy as
local curative treatment options within the framework of different multimodality
treatments for patients with locally advanced non-small cell lung cancer (NSCLC).
Endpoints for comparison of treatment results were overall survival, progression
free survival, and toxicity.Hazard ratios (HR) were taken to measure treatment
effects and pooled using a random effects model.Overall survival was not
significantly different between surgical and definitive radiotherapy arms
(HR=0.92 [95%CI 0.82-1.04], p=0.19, chi2-test). There was heterogeneity with
respect to survival at 2 years (p<0.0001, Cochran Mantel Haenszel (CMH)-test).
Latter trials using concurrent radiochemotherapy (ccRT/CT) showed better survival
at 2 years (risk ratio of death=0.80 [95%CI 0.73-0.88], p<0.0001, CMH-test). In
the ccRT/CT trials, survival in the surgical arms tended to have an excess early
mortality before 6 months of follow-up and a lesser hazard rate in comparison to
definitive ccRT/CT thereafter (HR=0.78 [95%CI 0.63-0.98]). Over all trials,
treatment associated mortality was higher in the surgical arms (risk ratio=3.56
[95% CI: 1.65-7.72], p=0.0005, CMH test). With respect to progression-free
survival, no significant differences were found (HR=0.91 [95%CI: 0.73 - 1.13]),
although the largest conducted trial found an advantage for the surgical arm
(HR=0.77 [95%CI: 0.62-0.96]).Induction therapy followed by resection or
definitive radiochemotherapy represent valuable curative treatment options for
patients with stage III NSCLC, the individual treatment choice deserves careful
interdisciplinary evaluation and counseling. Based on the broad heterogeneity of
patient groups in these stages further research on predictive factors supporting
individual therapy selection is necessary.
PMID- 28415828
TI - Melatonin for the prevention and treatment of cancer.
AB - The epidemiological studies have indicated a possible oncostatic property of
melatonin on different types of tumors. Besides, experimental studies have
documented that melatonin could exert growth inhibition on some human tumor cells
in vitro and in animal models. The underlying mechanisms include antioxidant
activity, modulation of melatonin receptors MT1 and MT2, stimulation of
apoptosis, regulation of pro-survival signaling and tumor metabolism, inhibition
on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin
could also be utilized as adjuvant of cancer therapies, through reinforcing the
therapeutic effects and reducing the side effects of chemotherapies or radiation.
Melatonin could be an excellent candidate for the prevention and treatment of
several cancers, such as breast cancer, prostate cancer, gastric cancer and
colorectal cancer. This review summarized the anticancer efficacy of melatonin,
based on the results of epidemiological,experimental and clinical studies, and
special attention was paid to the mechanisms of action.
PMID- 28415834
TI - The surgical treatment of gastric cancer in the era of minimally invasive
surgery.
AB - Minimally invasive surgery is regarded as an alternative to conventional open
surgery in gastric cancer. More and more surgeons devote their efforts to reduce
surgical incision and acquire better recovery. Nowadays, laparoscopic distal
gastrectomy has been the standard method for early stage cancer with remarkable
advantage in short-term outcomes and is widely accepted by patients. The
indication of laparoscopic gastrectomy has been extended to local advanced
gastric cancer. However, the oncological safety has long been debated. Therefore,
large scale randomized controlled clinical trials are ongoing to confirm the
feasibility and safety in more advanced gastric cancer. With the accumulation of
surgical experience and development of instrument, several advanced techniques,
such as function preserving surgery, total laparoscopic anastomosis, sentinel
node navigation surgery, robotic assisted surgery and reduced port laparoscopic
gastrectomy have also been explored and applied to gastric cancer patient. All
these techniques could modify the extent of surgery, reduce the risk of
perioperative complications and generate potential better results in quality of
life. Although recent studies have confirmed the feasibility and safety of each
procedure, more evidence is required for further popularization of the newly
technique. Herein we describe the current status and evidence for surgical
treatment of gastric cancer in the era of minimally invasive surgery.
PMID- 28415835
TI - The role of chemotherapy in unresectable or metastatic adenocarcinoma of the
stomach and gastroesophageal junction.
AB - Gastric cancer including gastroesophageal junction adenocarcinomas are most
challenging and deadly cancers of the gastrointestinal tract. Gastric cancer has
a fatality-to-case ratio of 0.66, translating that nearly two thirds of newly
diagnosed patients will have disseminated disease and in need of systemic
therapy. Advanced gastric adenocarcinoma (AGC) is a heterogenous disease with
differences in geographical distribution, histopathology, and molecular subtypes.
Fluoropyrimidines (5-FU, S-1, and capecitabine), platinum compounds (cisplatin,
oxaliplatin), taxanes (paclitaxel, docetaxel), and the topoisomerase inhibitory
irinotecan are active drugs against AGC. The combination of fluoropyrimidines
with a platinum compound is the optimal first-line treatment. Trastuzumab (given
in combination with chemotherapy for HER2 positive tumors) and ramucirumab are
the only targeted agents approved by the food and drug administration for the
treatment in AGC for first and second line respectively. Efforts are being
directed to harness the immune system with checkpoint inhibitors and to combining
these drugs with chemotherapy in clinical trials. Genomic technology advancements
might provide us with the tools to create personalized treatment for AGC in the
near future with the goal to improve outcomes. In this article we aimed to review
current therapeutic regimens for AGC with an update of ongoing clinical trials.
PMID- 28415837
TI - Effects of a Spacer on the Phase Behavior of Gemini Surfactants in
Ethanolammonium Nitrate.
AB - The aggregation behavior of quaternary ammonium gemini surfactants (12-s-12) in a
protic ionic liquid, ethanolammonium nitrate (EOAN), was investigated by small
angle X-ray scattering, freeze-fracture transmission electron microscopy,
polarized optical microscopy, and rheological measurements. The rarely reported
nonaqueous two phases in the ionic liquid were observed at lower 12-s-12
concentrations. The upper phase was composed of micelles, whereas only the
surfactant unimers or multimers were detected in the low phase. At higher 12-s-12
concentrations, different aggregates were formed. The lamellar phase was observed
in the 12-2-12/EOAN system, whereas the normal hexagonal phases in 12-s-12/EOAN
(s = 3, 4, 5, 6, 8) systems and the micellar phase in the 12-10-12/EOAN system
were observed. Such a dramatic phase transition induced by the spacer chain
length was due to the unique solvent characteristics of EOAN compared to those of
water and its counterpart ethylammonium nitrate.
PMID- 28415838
TI - A Fluorescent Probe for Hydrogen Peroxide in Vivo Based on the Modulation of
Intramolecular Charge Transfer.
AB - Endogenous hydrogen peroxide in vivo is related to many diseases, including
cancer, diabetes, cardiovascular disease, and neurodegenerative disorders.
Although many probes for detection of H2O2 have been explored, rapid response
probes are still expected for in vivo application. Here, a new probe (PAM-BN-PB)
was designed based on an intramolecular charge transfer (ICT) process with three
parts: phenanthroimidazole, benzonitrile, and phenyl boronate. By modulation ICT
process of PAM-BN-PB, H2O2 in solution systems can be detected with good
selectivity. The exogenous and endogenous H2O2 in normal living cells, ischemia
reperfusion injury cells, and animals all can be imaged by PAM-BN-PB.
PMID- 28415836
TI - Diabetic cardiomyopathy: where we are and where we are going.
AB - The global burden of diabetes mellitus and its related complications are
currently increasing. Diabetes mellitus affects the heart through various
mechanisms including microvascular impairment, metabolic disturbance, subcellular
component abnormalities, cardiac autonomic dysfunction, and a maladaptive immune
response. Eventually, diabetes mellitus can cause functional and structural
changes in the myocardium without coronary artery disease, a disorder known as
diabetic cardiomyopathy (DCM). There are many diagnostic tools and management
options for DCM, although it is difficult to detect its development and
effectively prevent its progression. In this review, we summarize the current
research regarding the pathophysiology and pathogenesis of DCM. Moreover, we
discuss emerging diagnostic evaluation methods and treatment strategies for DCM,
which may help our understanding of its underlying mechanisms and facilitate the
identification of possible new therapeutic targets.
PMID- 28415839
TI - Enantioselective Synthesis of anti-syn-Trihalides and anti-syn-anti-Tetrahalides
via Asymmetric beta-Elimination.
AB - Structural motifs containing contiguous halide-bearing stereocenters are common
in natural products as well as bioactive molecules. A few successful examples
have been reported in the area of asymmetric vicinal dihalogenation of alkenes
for accessing dihalogenated products; in this report, an alternative generation
method of contiguous halide-bearing stereocenters alpha,beta,gamma,delta relative
to carbonyl group in excellent enantioselectivity is proposed by utilizing a
Song's oligoEG catalyst-catalyzed asymmetric beta-elimination. According to this
methodology, a wide range of anti-syn-trihalides and anti-syn-anti-tetrahalides
with high levels of enantioselectivity were synthesized. The synthetic utility of
the contiguous halide-bearing stereocenters was demonstrated by several
transformations. The results of high-resolution mass spectrometry indicated that
the favorable interaction between catalyst and one of the enantiomers of racemic
contiguously multihalogenated ketone contributed to the original
enantioselectivity of dehydrohalogenation. A deuterium kinetic isotope effect
experiment revealed that this beta-elimination reaction proceeds by the E2
mechanism. This strategy opens a new pathway for the asymmetric synthesis of
contiguous halide-bearing stereocenters of great complexity.
PMID- 28415840
TI - Coexistence of Topological Edge State and Superconductivity in Bismuth Ultrathin
Film.
AB - Ultrathin freestanding bismuth film is theoretically predicted to be one kind of
two-dimensional topological insulators. Experimentally, the topological nature of
bismuth strongly depends on the situations of the Bi films. Film thickness and
interaction with the substrate often change the topological properties of Bi
films. Using angle-resolved photoemission spectroscopy, scanning tunneling
microscopy or spectroscopy and first-principle calculation, the properties of
Bi(111) ultrathin film grown on the NbSe2 superconducting substrate have been
studied. We find the band structures of the ultrathin film is quasi-freestanding,
and one-dimensional edge state exists on Bi(111) film as thin as three bilayers.
Superconductivity is also detected on different layers of the film and the
pairing potential exhibits an exponential decay with the layer thicknesses. Thus,
the topological edge state can coexist with superconductivity, which makes the
system a promising platform for exploring Majorana Fermions.
PMID- 28415841
TI - Unique Pattern of Protein-Bound Maillard Reaction Products in Manuka
(Leptospermum scoparium) Honey.
AB - As a unique feature, honey from the New Zealand manuka tree (Leptospermum
scoparium) contains substantial amounts of dihydroxyacetone (DHA) and
methylglyoxal (MGO). Although MGO is a reactive intermediate in the Maillard
reaction, very little is known about reactions of MGO with honey proteins. We
hypothesized that the abundance of MGO should result in a particular pattern of
protein-bound Maillard reaction products (MRPs) in manuka honey. A protein-rich
high-molecular-weight fraction was isolated from 12 manuka and 8 non-manuka
honeys and hydrolyzed enzymatically. By HPLC-MS/MS, 8 MRPs, namely, N-epsilon
fructosyllysine, N-epsilon-maltulosyllysine, carboxymethyllysine,
carboxyethyllysine (CEL), pyrraline, formyline, maltosine, and methylglyoxal
derived hydroimidazolone 1 (MG-H1), were quantitated. Compared to non-manuka
honeys, the manuka honeys were characterized by high concentrations of CEL and MG
H1, whereas the formation of N-epsilon-fructosyllysine was suppressed, indicating
concurrence reactions of glucose and MGO at the epsilon-amino group of protein
bound lysine. Up to 31% of the lysine and 8% of the arginine residues,
respectively, in the manuka honey protein can be modified to CEL and MG-H1,
respectively. CEL and MG-H1 concentrations correlated strongly with the MGO
concentration of the honeys. Manuka honey possesses a special pattern of protein
bound MRPs, which might be used to prove the reliability of labeled MGO levels in
honeys and possibly enable the detection of fraudulent MGO or DHA addition to
honey.
PMID- 28415842
TI - Spectrophotometric Quantification of Peroxidase with p-Phenylene-diamine for
Analyzing Peroxidase-Encapsulating Lipid Vesicles.
AB - A spectrophotometric assay for the determination of horseradish peroxidase (HRP)
in aqueous solution with p-phenylenediamine (PPD, benzene-1,4-diamine) as
electron donor substrate and hydrogen peroxide (H2O2) as oxidant was developed.
The oxidation of PPD by HRP/H2O2 leads to the formation of Bandrowski's base
((3E,6E)-3,6-bis[(4-aminophenyl)imino]cyclohexa-1,4-diene-1,4-diamine), which can
be quantified by following the increase in absorbance at 500 nm. The assay was
applied for monitoring the activity of HRP inside ~180 nm-sized lipid vesicles
(liposomes), prepared from POPC (1-palmitoyl-2-oleoyl-sn-glycero-3
phosphocholine) and purified by size exclusion chromatography. Because of the
high POPC bilayer permeability of PPD and H2O2, the HRP-catalyzed oxidation of
PPD occurs inside the vesicles once PPD and H2O2 are added to the vesicle
suspension. In contrast, if instead of PPD the bilayer-impermeable substrate
ABTS2- (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate)) is used, the
oxidation of ABTS2- inside the vesicles does not occur. Therefore, using PPD and
ABTS2- in separate assays allows distinguishing between vesicle-trapped HRP and
HRP in the external bulk solution. In this way, the storage stability of HRP
containing POPC vesicles was investigated in terms of HRP leakage and activity of
entrapped HRP. It was found that pH 7.0 suspensions of POPC vesicles (2.2 mM
POPC) containing on average about 12 HRP molecules per vesicle are stable for at
least 1 month without any significant HRP leakage, if stored at 4 degrees C.
Such high stability is beneficial not only for bioanalytical applications but
also for exploring the kinetic properties of vesicle-entrapped HRP through simple
spectrophotometric absorption measurements with PPD as a sensitive and cheap
substrate.
PMID- 28415843
TI - Structure, Stability, and Electronic and Magnetic Properties of VGen (n = 1-19)
Clusters.
AB - We systematically study the equilibrium geometries and electronic and magnetic
properties of Gen+1 and VGen (n = 1-19) clusters using the density functional
theory approach within the generalized gradient approximation. Endohedral
structures in which the vanadium atom is encapsulated inside a Gen cage are
predicted to be favored for n >= 10. The dopant V atom in the Gen clusters has
not an immediate effect on the stability of small germanium clusters (n < 6), but
it largely contributes to strengthen the stability for n >= 7. Our study enhances
the large stability of the VGe14 cluster, which presents an Oh symmetry cagelike
geometry and a peculiar electronic structure in which the valence electrons of V
and Ge atoms are delocalized and exhibit a shell structure associated with the
quasi-spherical geometry. Consequently, this cluster is proposed to be a good
candidate to be used as the building blocks for developing new materials. The
cluster size dependence of the stability, the vertical ionization potentials, and
electron affinities of Gen+1 and VGen are presented. Magnetic properties and the
partial density of states of the most stable VGen clusters are also discussed.
PMID- 28415844
TI - Stimuli-Controlled Hydrogels and Their Applications.
PMID- 28415845
TI - What does 'rural return' mean? Rural-origin medical graduates do not 'go home'.
PMID- 28415847
TI - Synthesis and antitumour activity of arctigenin amino acid ester derivatives
against H22 hepatocellular carcinoma.
AB - Arctigenin (ARG) is famous in its abundant pharmacological activity. However,
many researches in it entered the bottleneck period because of its poor water
solubility. The derivatives of ARG have been synthesised with five amino acids
which have t-Butyloxy carbonyl (BOC) as a protective group. We examined the
effects of removing BOC. The results showed that the amino acid derivatives
without protective group have better water solubility and nitrite-clearing
ability than ARG. Based on these results, ARG6' and ARG9' were selected at a
dosage of 40 mg/kg to evaluate their antitumour activity. The percentage
inhibition rate of ARG6' and ARG9' were 55.87 and 51.40, respectively, which was
twice as much as ARG. Furthermore, they could increase liver and kidney indexes
and produce less damage in these organs. In brief, this study provides a basis
for new drug development.
PMID- 28415848
TI - Increased Carotid Intima-Media Thickness in Obstructive Sleep Apnea: An
Additional Issue to Consider.
PMID- 28415846
TI - Is urban-rural location associated with weight status in school children? An
examination of 42 small and rural Californian counties.
AB - INTRODUCTON: Studies have identified geographic variation in overweight and
obesity rates among children, with higher rates of overweight and obesity often
found among children living in rural compared to urban areas. A small number of
studies have explored differences in overweight and obesity based on more nuanced
gradations along the urban-rural continuum. The purpose of the present study was
to identify differences in overweight and obesity based on gradations along the
urban-rural continuum among children in 42 Californian counties with populations
less than 500 000. METHODS: An observational study was conducted using
FITNESSGRAM data collected from 5th, 7th and 9th grade students in public schools
in California during 2010-2011. The FITNESSGRAM dataset was merged with the 2011
Public Elementary/Secondary School Universe Survey Data from the National Center
for Educational Statistics Common Core of Data, which includes an 'urban-centric
locale' code for each school, consisting of four broad classifications - city,
suburb, town, and rural - each of which is further broken down into three
subcategories. Multivariate analyses using a general linear model were conducted
to compare differences in body mass index (BMI) between geographic regions of
schools (city, suburb, town and rural) as well as 11 urban-centric locale code
subcategories; none of the schools were located in large cities. The percentage
of students who were overweight and/or obese was compared by grade level, gender,
and race/ethnicity across geographic regions using multivariate logistic
regression models. Analyses were adjusted for student age, grade, gender,
race/ethnicity (African-American, Asian, Hispanic, Indian/Alaskan, White, two or
more races or unknown), eligibility for free or reduced price meals, and
clustering of students by school. When a stratified analysis was done, the
variable of stratification (ie grade, gender, race/ethnicity) was not included
among the covariates. When significant differences in BMI or prevalence of
overweight or obesity were found between geographic regions, Tukey's method was
applied to adjust for multiple comparisons at a 5% procedure-wise error rate. A
p-value at or less than 0.05 was used to indicate statistical
significance. RESULTS: Students in suburban schools had significantly lower mean
BMI and lower prevalence of overweight than students in other geographic areas
(p<0.0001). Among 5th and 7th grade students, prevalence of obesity (but
not overweight) varied by urban-rural status (p<0.0001, p=0.01,
respectively), with 7th grade students in suburbs having lower rates of obesity
than those in towns. Among 9th grade students, prevalence of overweight (but not
obesity) varied by urban-rural status (p=0.02). Among females, prevalence
of overweight and obesity varied (p=0.006, p<0.0001, respectively),
with suburbs having lower rates than cities and towns. Among males, prevalence of
obesity varied (p<0.0001), with suburbs having lower rates. Among whites,
there were differences in prevalence of overweight and obesity by urban-rural
status (p=0.01, p <0.0001, respectively). Among Hispanics, the
prevalence of obesity varied by urban-rural status (p=0.001). Large
suburban areas had the lowest rates of obesity compared to all other
subcategories. CONCLUSIONS: Students attending schools in suburban, especially
larger suburban, areas appear to have lower prevalence of obesity than their
peers at schools in other geographic areas. Further research is needed to
understand the factors associated with differences in weight status between
urban, suburban, town and rural areas.
PMID- 28415849
TI - Final Say on Research Into Population Screening for Abdominal Aortic Aneurysm.
PMID- 28415850
TI - A new iridoid glycoside from the fruits of Vitex rotundifolia.
AB - One new iridoid glycoside, 6',10-di-O-(4-hydroxybenzoyl) aucubin (1), together
with ten known compounds, including five diterpenoids (2-6), two triterpene
glucosides (7-8) and three methoxylated flavonoids (9-11) were isolated from the
fruits of Vitex rotundifolia. Compounds (3, 4, 7, and 8) were reported for the
first time from this plant. Their structures were elucidated by spectral analysis
and by comparison with literature data. Furthermore, some of the isolated
compounds were evaluated for their cytotoxicities against A549 and HepG-2 cell
lines using MTT assay, and only compounds 9 and 10 exhibited potent cytotoxic
activity with IC50 values of 13 +/- 4 and 35 +/- 10 MUM against HepG-2 cell
lines.
PMID- 28415851
TI - Over-education and well-being: how does education-occupation mismatch affect the
life satisfaction of university-educated immigrant and non-immigrant workers?
AB - OBJECTIVE: The increased migration of skilled workers has resulted in a focus on
the economic costs of their unsuccessful labor market integration. Few studies
investigate the consequences of employment difficulties on immigrants' well
being. Researchers studying over-education and life satisfaction tend to only
examine the general population despite high levels of over-education among
skilled immigrants. This study examines the relationship between over-education
and life satisfaction among both immigrant and native-born workers in Canada.
Factors associated with immigrants specifically (e.g. years since migration) are
also considered. DESIGN: Descriptive and multivariate analyses are conducted
using pooled data from the 2009 to 2014 Canadian Community Health Survey (CCHS).
Ordinary-least-squares (OLS) regression models are estimated with life
satisfaction as the outcome. The models are run separately for immigrant and
Canadian-born workers, accounting for differences in the degree to which
individuals are over-educated. There are 5826 immigrant respondents and 24,985
non-immigrant respondents. RESULTS: Over-education was negatively associated with
the life satisfaction of both immigrants and non-immigrants, although the effect
was weaker among the immigrant population. Income was the main factor mediating
the negative relationship between over-education and life satisfaction among
immigrants. Moreover, the negative influence of over-education on life
satisfaction weakened with immigrants' increased residence in Canada. CONCLUSION:
Although over-education was negatively associated with immigrants' life
satisfaction, it had a stronger influence on the non-immigrant population. This
may be due to differences in the reference groups to which immigrants and non
immigrants compare themselves when assessing their life satisfaction; over
education may be less influential to immigrants' life satisfaction because it is
a common experience among immigrants. Additionally, over-education is less
detrimental to immigrants' life satisfaction with increased time in the host
country. This may be attributable to a shift in the importance immigrants assign
to the employment domain of their life over time.
PMID- 28415852
TI - Internal health locus of control predicts willingness to track health behaviors
online and with smartphone applications.
AB - Given rising technology use across all demographic groups, digital interventions
offer a potential strategy for increasing access to health information and care.
Research is lacking on identifying individual differences that impact willingness
to use digital interventions, which may affect patient engagement. Health locus
of control, the amount of control an individual believes they have over their own
health, may predict willingness to use mobile health (mHealth) applications
('apps') and online trackers. A cross-sectional study (n = 276) was conducted to
assess college students' health locus of control beliefs and willingness to use
health apps and online trackers. Internal and powerful other health locus of
control beliefs predicted willingness to use health apps and online trackers
while chance health locus of control beliefs did not. Individuals with internal
and powerful other health locus of control beliefs are more willing than those
with chance health locus of control beliefs to utilize a form of technology to
monitor or change health behaviors. Health locus of control is an easy-to-assess
patient characteristic providers can measure to identify which patients are more
likely to utilize mHealth apps and online trackers.
PMID- 28415853
TI - Promoting Parent and Child Physical Activity Together: Elicitation of Potential
Intervention Targets and Preferences.
AB - Promoting physical activities that involve both parents and their children would
be very useful to the improved health and well-being of families, yet coactivity
interventions have been particularly unsuccessful in past research. The purpose
of this study was to elicit the salient parental beliefs about coactivity framed
through theory of planned behavior in order to inform future intervention
content. A representative sample of Canadian parents ( N = 483) with children
aged 6 to 14 years completed belief elicitation measures of theory of planned
behavior, as well as coactivity and program preferences. Analyses included
content theming by physical activity belief and preference through tallies of the
percentages of parents endorsing each belief. Exploratory analyses of differences
in endorsed themes were conducted by parent (mother, father), age of child (6-10
years, 11-14 years), and sex of the child. The results showed that behavioral
beliefs about health, interpersonal and educational/learning opportunities and
control beliefs about lack of time, various incompatible parent/child factors,
parental health, and bad weather were dominant themes. Most of these themes did
not vary in endorsement by parent and child characteristics. By contrast,
preferences for various activities varied by parent and child characteristics,
yet parents overwhelmingly desired the activities to be outdoors, close to home,
after work, and originally delivered from community health professionals via
Internet or face-to face means. Overall, the findings provide several
considerations for specific targets to improve future physical activity
intervention approaches among parents and their children.
PMID- 28415854
TI - New phenolic acids from Salvia yunnanensis C.H.Wright.
AB - Two new phenolic acids, ethyl pro-lithospermate (1), n-butyl pro-lithospermate
(2) were isolated from Salvia yunnanensis C.H.Wright, along with nineteen known
compounds (3-21). The structures of the isolated compounds were elucidated on the
basis of extensive spectrometry and by comparing their physical and spectroscopic
data to the literature. Among them, compounds 11, 12 and 14-16 were firstly
isolated from S. yunnanensis C.H.Wright. Some of the isolated compounds were
evaluated for their neuroprotection. Compounds 10-12 showed significant
neuroprotective effects in PC12 cells and compounds 1, 4-7 displayed moderate
neuroprotective effects.
PMID- 28415855
TI - Predicting jet lag in long-haul cabin crew: The role of illness cognitions and
behaviour.
AB - OBJECTIVE: Established risk factors for jet lag are mostly physiological
including circadian preference, age, gender, the number of flight zones crossed
and to some extent direction of travel. Some research has also highlighted a role
for psychosocial factors including sleep, diet and 'circadian' health behaviours
and illness cognitions although this remains relatively untested. The aim of this
study was to evaluate the role of sleep, diet and illness cognitions in
predicting perceived jet lag amongst long-haul crew. DESIGN: Sixty long-haul crew
took part in a longitudinal study. Profile characteristics (including
chronotype), preparation strategies (sleep, eating and 'circadian' behaviours)
and illness cognitions were measured at baseline (before a trip). MAIN OUTCOME
MEASURES: Subjective jet lag (unidimensional and multidimensional) was measured
on the crews' second day off (post-trip). RESULTS: Hierarchical regression
analyses showed that unidimensional jet lag was predicted by the belief in a
cyclical timeline, whereas multidimensional jet lag was predicted by
multidimensional jet lag at baseline and to a lesser extent by identity. No role
was found for profile characteristics and preparation strategies. CONCLUSION:
Illness cognitions partly explain the experience of perceived jet lag in long
haul cabin crew indicating that jet lag is in part a psycho-social construct, not
just a biological one.
PMID- 28415856
TI - Gene and Variant Annotation for Mendelian Disorders in the Era of Advanced
Sequencing Technologies.
AB - Comprehensive annotations of genetic and noncoding regions and corresponding
accurate variant classification for Mendelian diseases are the next big challenge
in the new genomic era of personalized medicine. Progress in the development of
faster and more accurate pipelines for genome annotation and variant
classification will lead to the discovery of more novel disease associations and
candidate therapeutic targets. This ultimately will facilitate better patient
recruitment in clinical trials. In this review, we describe the trends in
research at the intersection of basic and clinical genomics that aims to increase
understanding of overall genomic complexity, complex inheritance patterns of
disease, and patient-phenotype-specific genomic associations. We describe the
emerging field of translational functional genomics, which integrates other
functional "-omics" approaches that support next-generation sequencing genomic
data in order to facilitate personalized diagnostics, disease management,
biomarker discovery, and medicine. We also discuss the utility of this integrated
approach for diagnostic clinics and medical databases and its role in the future
of personalized medicine.
PMID- 28415858
TI - Recent Advances in Mitochondrial Disease.
AB - Mitochondrial disease is a challenging area of genetics because two distinct
genomes can contribute to disease pathogenesis. It is also challenging clinically
because of the myriad of different symptoms and, until recently, a lack of a
genetic diagnosis in many patients. The last five years has brought remarkable
progress in this area. We provide a brief overview of mitochondrial origin,
function, and biology, which are key to understanding the genetic basis of
mitochondrial disease. However, the primary purpose of this review is to describe
the recent advances related to the diagnosis, genetic basis, and prevention of
mitochondrial disease, highlighting the newly described disease genes and the
evolving methodologies aimed at preventing mitochondrial DNA disease
transmission.
PMID- 28415859
TI - The missing link? The potential role of selenium in the development of liver
cancer and significance for the general population.
PMID- 28415860
TI - Computer-Mediated Social Support for Physical Activity: A Content Analysis.
AB - PURPOSE: Online fitness communities are a recent phenomenon experiencing growing
user bases. They can be considered as online social networks in which recording,
monitoring, and sharing of physical activity (PA) are the most prevalent
practices. They have added a new dimension to the social experience of PA in
which online peers function as virtual PA partners or supporters. However,
research into seeking and receiving computer-mediated social support for PA is
scarce. Our aim was to study to what extent using online fitness communities and
sharing physical activities with online social networks results in receiving
various types of online social support. METHOD: Two databases, one containing
physical activities logged with Strava and one containing physical activities
logged with RunKeeper and shared on Twitter, were investigated for occurrence and
type of social support, by means of a deductive content analysis. RESULTS:
Results indicate that social support delivered through Twitter is not
particularly extensive. On Strava, social support is significantly more
prevalent. Especially esteem support, expressed as compliments for the
accomplishment of an activity, is provided on both Strava and Twitter.
CONCLUSION: The results demonstrate that social media have potential as a
platform used for providing social support for PA, but differences among various
social network sites can be substantial. Especially esteem support can be
expected, in contrast to online health communities, where information support is
more common.
PMID- 28415861
TI - Atmospheric Aerosols: Clouds, Chemistry, and Climate.
AB - Although too small to be seen with the human eye, atmospheric particulate matter
has major impacts on the world around us, from our health to global climate.
Understanding the sources, properties, and transformations of these particles in
the atmosphere is among the major challenges in air quality and climate research
today. Significant progress has been made over the past two decades in
understanding atmospheric aerosol chemistry and its connections to climate.
Advances in technology for characterizing aerosol chemical composition and
physical properties have enabled rapid discovery in this area. This article
reviews fundamental concepts and recent developments surrounding ambient
aerosols, their chemical composition and sources, light-absorbing aerosols,
aerosols and cloud formation, and aerosol-based solar radiation management (also
known as solar geoengineering).
PMID- 28415857
TI - Sharing Data to Build a Medical Information Commons: From Bermuda to the Global
Alliance.
AB - The Human Genome Project modeled its open science ethos on nematode biology, most
famously through daily release of DNA sequence data based on the 1996 Bermuda
Principles. That open science philosophy persists, but daily, unfettered release
of data has had to adapt to constraints occasioned by the use of data from
individual people, broader use of data not only by scientists but also by
clinicians and individuals, the global reach of genomic applications and diverse
national privacy and research ethics laws, and the rising prominence of a diverse
commercial genomics sector. The Global Alliance for Genomics and Health was
established to enable the data sharing that is essential for making meaning of
genomic variation. Data-sharing policies and practices will continue to evolve as
researchers, health professionals, and individuals strive to construct a global
medical and scientific information commons.
PMID- 28415862
TI - Multivariate Analysis and Statistics in Pharmaceutical Process Research and
Development.
AB - The application of statistics in pharmaceutical process research and development
has evolved significantly over the past decades, motivated in part by the
introduction of the Quality by Design paradigm, a landmark change in regulatory
expectations for the level of scientific understanding associated with the
manufacturing process. Today, statistical methods are increasingly applied to
accelerate the characterization and optimization of new drugs created via
numerous unit operations well known to the chemical engineering discipline. We
offer here a review of the maturity in the implementation of design of experiment
techniques, the increased incorporation of latent variable methods in process and
material characterization, and the adoption of Bayesian methodology for process
risk assessment.
PMID- 28415863
TI - Thermophysical Properties and Phase Behavior of Fluids for Application in Carbon
Capture and Storage Processes.
AB - Phase behavior and thermophysical properties of mixtures of carbon dioxide with
various other substances are very important for the design and operation of
carbon capture and storage (CCS) processes. The available empirical data are
reviewed, together with some models for the calculation of these properties. The
systems considered in detail are, first, mixtures of carbon dioxide, water, and
salts; second, carbon dioxide-rich nonelectrolyte mixtures; and third, mixtures
of carbon dioxide with water and amines. The empirical data and the plethora of
available models permit the estimation of key fluid properties required in the
design and operation of CCS processes. The engineering community would benefit
from the further development, and delivery in convenient form, of a small number
of these models sufficient to encompass the component slate and operating
conditions of CCS processes.
PMID- 28415864
TI - [Extrahepatic manifestations in chronic hepatitis C infected patients].
AB - The importance of chronic hepatitis C infection is significant. 3% of the World's
population is infected. There is at least one extrahepatic manifestation in 50%
of HCV patients, which makes the prognosis and mortality worse. The
pathomechanisms included are cryoglobulin production, immunmechanisms, and direct
viral effects. The authors summarize the main extrahepatic manifestations, as
well as treatment possibilities. The aim is to draw attention to this colourful
infection in order to improve the recognition in the era of the new effective
direct antiviral agents. Orv. Hetil., 2017, 158(16), 603-612.
PMID- 28415867
TI - [Supporting Semmelweis in French in 1849 in Strasbourg - the unfairly forgotten
Friedrich Wieger (1821-1890)].
PMID- 28415865
TI - [Placental gene activity of significant angiogenetic factors in the background of
intrauterine growth restriction].
AB - Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene
are both overexpressed in placental samples obtained from pregnancies with
intrauterine growth restriction compared to normal pregnancies. In the background
of these changes a mechanism can be supposed, in which the increased endoglin
activity in intrauterine growth restriction (IUGR) leads to impaired placental
circulation through an antioangiogenetic effect. This results in the development
of placental vascular dysfunction and chronic fetal hypoxia. It is chronic
hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal
vascular blood supply by promoting placental blood vessel formation. Although the
maternal serum placental growth factor (PlGF) level is a potential predictor for
both IUGR and praeeclampsia, placental PlGF gene activity may be less of an
active in the regulation of placental circulation in IUGR pregnancies during the
later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.
PMID- 28415868
TI - [Epidemiological data of Hungarian skiers' and snowboarders' medical problems].
AB - INTRODUCTION AND AIM: There are no high mountains or any advantageous
circumstances for winter sports in Hungary, yet within the 10 million population
there are about half a million people (the exact number is 550,000) who tend to
go for skiing or snowboarding abroad. Authors compared the injury statistical
data with results described in the international literature in order to develop
conclusions about the differences in the injury patterns and frequency between
the Hungarian ones' and those found in countries with plenty of winter sport
possibilities. METHOD: Authors analysed the winter sport injury cases of an
insurance company. All the injury happened abroad and the assistance provider of
the insurance company has managed the patient treatment and repatriation. Three
winter seasons (12 months) data was analysed from the point of view of injuries
frequency at different body parts and areas. Due to the fact that only limited
information was available a simple statistical method was applied. RESULTS: Of
222 cases 90.5% were ski-related injury and 8.6% were snowboard injury. As for
the skiers, the upper limb injuries accounted for 21.9%, the truncal region for
24.4% and the lower limb for 55.8%. Among snowboarders the upper limb injuries
accounted for 36.9%, the truncal region for 37% and the lower limb for 26.1%. The
most frequent was the knee (36.8%), the wrist (12.4) and the shoulder (11.4)
injury. Skier's thumb injury was only 1.5%. The most common snowboard injury was
the wrist trauma (31.6%), the head/neck/face was accounted 15.8% of all the
injuries. And the ankle was injured in 10.5% of all the cases. The head/neck and
the knee injury often combined with injuries of some other body part. 29 patients
(13%) had to be repatriated, the most frequent reason for the repatriation was
the injury of the lower limb. CONCLUSIONS: The Hungarian sportsmen's injury
patterns do not always follow data described in the international literature, but
they correspond to data of countries with similar geographical situation. The
injury rate of knee and of the shoulder displays same data, the injury rate of
the wrist was more frequent than in the international data, and this is true both
for skiers and the snowboarders. The Hungarians' injury of the truncal region
(mainly the head) was more frequent, but on the other hand the general injury
rate of other body parts proved to be a lower number. It seems that the frequent
use of the protective equipment and the preventive measures applied by the
Hungarians are mirrored in the lower injury figures. Orv. Hetil., 2017, 158(16),
618-624.
PMID- 28415869
TI - [Types of conflicts and conflict management among Hungarian healthcare workers].
AB - INTRODUCTION: Efficient communication, conflict management and cooperation are
the key factors of a successful patient care. AIM: This study is part of an
international comparative research. The aim of this study is to unfold conflicts
among healthcare workers. METHOD: 73 healthcare workers were interviewed using a
standardized interview protocol. The in-person interviews used the critical
incident method. 30 interviews (15 doctors, 15 nurses) were analysed with the
Atlas.ti 7 content analysis software. The sources, types, effects of conflicts
and conflict management strategies were investigated. RESULTS: The content
analysis unfolded the specificities of conflicts in healthcare based on personal
experiences. Organizational hierarchy was a substantial source of conflict,
especially among physicians, which originates from implicit rules. As a result of
the avoiding conflict management the conflicts remain partly unresolved which has
negative individual and group effect. CONCLUSIONS: Our conceptual framework helps
to develop a proper intervention specific to healthcare. Orv. Hetil., 2017,
158(16), 625-632.
PMID- 28415870
TI - Longitudinal changes in the antecedent and early manifest course of bipolar
disorder-A narrative review of prospective studies.
AB - OBJECTIVE: Prospective study designs ideally allow patients to be followed from
the first manifestations of the illness or even from an at-risk stage. It can
thus provide data on the predictive value of changes in clinical symptomatology,
cognition or further biological markers to broaden our understanding of the
etiopathology and symptomatic trajectory of bipolar disorders. The scope of this
narrative review is to summarize evidence from prospectively collected data on
psychopathological and other clinical and biological changes in the early
developmental course of bipolar disorders. METHODS: The narrative review was
based on a literature search conducted in February 2016 within the PubMed library
for prospective study data of persons in antecedent and early manifest stages of
manifest bipolar disorder published within the last 15 years. RESULTS: A total of
19 prospective studies were included. Regarding psychopathological features;
personality, temperament and character traits as well as changes in sleep and
circadian rhythm, the evidence suggests that risk factors for the development of
bipolar disorder can already be described and should be studied further to
understand their interaction, mediation with other factors and timing in the
developmental process of bipolar disorder. Apart from the positive family
history, childhood anxiety, sleep problems, subthreshold (hypo)manic symptoms and
certain character traits/emotionality should be identified and monitored already
in clinical practice as their presence likely increases risk of bipolar disorder.
Up to date no substantiated evidence was found from prospective studies
addressing cognitive features, life events, immunological parameters and
morphological central nervous system changes as potential risk factors for
bipolar disorder. CONCLUSION: For an improved understanding of episodic
disorders, longitudinal data collection is essential. Since the etiology of
bipolar disorders is complex, a number of potential risk factors have been
proposed. Prospective studies addressing this spectrum and resilience factors are
critical and will be best conducted within multi-site research networks or
initiatives.
PMID- 28415871
TI - Back to the future: Schizophrenia in retrospect and prospect.
PMID- 28415872
TI - Taking a look into the future: Do clinical and neurobiological trajectories tell
us more than what we already know?
PMID- 28415873
TI - Structural brain changes in schizophrenia at different stages of the illness: A
selective review of longitudinal magnetic resonance imaging studies.
AB - OBJECTIVE: Schizophrenia is a devastating mental disorder accompanied by aberrant
structural brain connectivity. The question whether schizophrenia is a
progressive brain disorder is yet to be resolved. Thus, it is not clear when
these structural alterations occur and how they develop over time. METHODS: In
our selective review, we summarized recent findings from longitudinal magnetic
resonance imaging studies investigating structural brain alterations and its
impact on clinical outcome at different stages of the illness: (1) subjects at
ultra-high risk of developing psychosis, (2) patients with a first episode
psychosis, and (3) chronically ill patients. Moreover, we reviewed studies
examining the longitudinal effects of medication on brain structure in patients
with schizophrenia. RESULTS: (1) Studies from pre-clinical stages to conversion
showed a more pronounced cortical gray matter loss (i.e. superior temporal and
inferior frontal regions) in those individuals who later made transition to
psychosis. (2) Studies investigating patients with a first episode psychosis
revealed a decline in multiple gray matter regions (i.e. frontal regions and
thalamus) over time as well as progressive cortical thinning in the superior and
inferior frontal cortex. (3) Studies focusing on patients with chronic
schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal
and temporal areas, thalamus, and cingulate cortices)-especially in poor-outcome
patients. Very few studies reported effects on white matter microstructure in the
longitudinal course of the illness. CONCLUSION: There is adequate evidence to
suggest that schizophrenia is associated with progressive gray matter
abnormalities particularly during the initial stages of illness. However, causal
relationships between structural changes and illness course-especially in
chronically ill patients-should be interpreted with caution. Findings might be
confounded by longer periods of treatment and higher doses of antipsychotics or
epiphenomena related to the illness.
PMID- 28415874
TI - Making Early Intervention more equitable.
PMID- 28415875
TI - The ideal mood stabiliser: A quest for nirvana?
PMID- 28415876
TI - Phenomenal Insights: Extraordinary auditory hallucinations-Thought sonorisation.
PMID- 28415877
TI - The portrayal of psychiatry in popular culture: Harmful or helpful?
PMID- 28415878
TI - Predicting bipolar disorder: Vitally important, clinically difficult.
PMID- 28415879
TI - Depressive symptom trajectories in late adolescence and early adulthood: A
systematic review.
AB - OBJECTIVE: In adolescents and young adults, depressive symptoms are highly
prevalent and dynamic. For clinicians, it is difficult to determine whether a
young person reporting depressive symptoms is at risk of developing ongoing mood
difficulties or whether symptoms form part of a transient maturational process.
Trajectory analyses of longitudinally assessed symptoms in large cohorts have the
potential to untangle clinical heterogeneity by determining subgroups or classes
of symptom course and their risk factors, by interrogating the impact of known or
suspected risk factors on trajectory slope and intercept and by tracing the
interrelation between depressive symptoms and other clinical outcomes over time.
METHOD: We conducted a systematic review of trajectory studies conducted in
cohorts including people aged between 15 and 25 years. RESULTS: We retrieved 47
relevant articles. These studies suggest that young people fall into common mood
trajectory classes and that class membership and symptom course are mediated by
biological and environmental risk factors. Furthermore, studies provide evidence
that high and persistent depressive symptoms are associated with a range of
concurrent health and behavioral outcomes. CONCLUSION: Findings could assist in
the formulation of novel concepts of depressive disorders in young people and
inform preventive strategies and predictive models for clinical practice.
PMID- 28415880
TI - Introductory paragraph.
PMID- 28415881
TI - Hip and pelvic fracture patients with fear of falling: development and
description of the "Step by Step" treatment protocol.
AB - OBJECTIVE: Based on a theoretical framework and sound evidence, this article
describes a rehabilitation programme for patients with fear of falling after hip
and pelvic fracture. RATIONALE: Based on exercise science principles, current
knowledge from fall prevention, emotion regulation, and the Health Action Process
Approach we developed a theoretical framework, from which the components of the
intervention were derived. Description of the intervention: The intervention
consists of 6 components: (1) relaxation, (2) meaningful activities and mobility
based goals, (3) falls related cognitions and emotions, coping with high risk
tasks and situations, (4) individual exercise programme, (5) planning and
implementing exercises and activities, and (6) fall risks and hazards. The
intervention comprises of 8 individual sessions during 3 to 5 weeks of inpatient
rehabilitation and 4 telephone calls and 1 home visit over a 2-month post
discharge period. Each session or telephone call takes about 30-60 minutes. It is
provided to geriatric hip and pelvic fracture patients with concerns about
falling and no cognitive impairment. To ensure completeness of reporting, the
Template for Intervention Description and Replication (TIDierR) is used. RESULTS:
Fifty-seven patients were assigned to the intervention group. All 46 completers
met all pre-defined criteria for an intervention per protocol. CONCLUSION: The
programme is feasible to administer. We have completed a randomised controlled
trial, which will be submitted in due time (for trial protocol: www.isrctn.org ;
ISRCTN79191813).
PMID- 28415882
TI - RAGE receptor targeted bioconjuguate lipid nanoparticles of diallyl disulfide for
improved apoptotic activity in triple negative breast cancer: in vitro studies.
AB - In the present study, we have demonstrated receptor for advanced glycation
endproducts (RAGE) as a target for delivery of drugs specifically to triple
negative breast cancer cells. We have prepared solid lipid nanoparticle
formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its
bioavailability issues. Then, we have surface modified DADS-loaded solid lipid
nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of
DADS to TNBC cells. We found a significant cellular internalization of RAGE
surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN. The
cytotoxic effect of DADS was also significantly improved with DADS-RAGE-SLN by
downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as
observed by western blot analysis. RAGE-targeted delivery of cytotoxic agents can
be, therefore, a promising approach for improving antitumour activity and
reducing off-target effects.
PMID- 28415883
TI - Electrosteric stealth Rivastigmine loaded liposomes for brain targeting:
preparation, characterization, ex vivo, bio-distribution and in vivo
pharmacokinetic studies.
AB - Being one of the highly effective drugs in treatment of Alzheimer's disease,
Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion
of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin,
Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A
major challenge during the preparation of liposomes is maintaining a stable
formulation, therefore the aim of our study was to increase liposomal stability
by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase
stability by steric hindrance, yielding what we called an electrosteric stealth
(ESS) liposomes. A medium nano-sized liposome (478 +/- 4.94 nm) with a nearly
neutral zeta potential (ZP, -8 +/- 0.2 mV) and an entrapment efficiency
percentage of 48 +/- 6.22 was prepared. Stability studies showed no major
alteration after three months storage period concerning particle size,
polydispersity index, ZP, entrapment efficiency and in vitro release study
confirming the successful formation of a stable liposomes. No histopathological
alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS
liposomes showed higher % of drug permeating through the sheep nasal mucosa
(48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic
studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma
levels of the formula ESS compared to that of RHT intranasal solution and 486%
relative bioavailability of the mean brain levels.
PMID- 28415884
TI - Alcohol quantification: recent insights into amperometric enzyme biosensors.
AB - Biosensors are the switching channels that make sense. The biosensors have found
an empirical role in health applications (e.g. clinical diagnostics) as they
represent the technological counterpart of living senses. On a global scale,
alcohol analysis is indispensable for criminal justice systems, monitoring
medical conditions of HIV patients & pregnant women as well as public safety
issues regarding pilots, metro drivers, doctors etc. For addressing the clinical
and toxicological problems, much advancement in the improvement of biosensors
have been witnessed in recent decades. Currently, electrochemical biosensors
dominate the field which harnesses the synergistic action of enzymes and
nanomaterials for the analysis of ethanol. The enzymatic biosensors are the most
explored biosensing devices among all the types of biosensors, and employment of
nanomaterials has paved a way to the further improvements in this gem of a
discovery. The relative comparison to precise the alcohol biosensors has been
aptly discussed in the review on the basis of several analytical properties
including fabrication, linearity, sensitivity, response time, detection limit as
well as storage stability. Finally, the recent trends and emerging future
prospects of alcohol biosensors have been reviewed.
PMID- 28415885
TI - Fatigue and pain limit independent mobility and physiotherapy after hip fracture
surgery.
AB - PURPOSE: The patient's ability to complete their planned physiotherapy session
after hip fracture surgery has been proposed as an independent predictor for
achieving basic mobility independency upon hospital discharge. However, knowledge
of factors limiting mobility is sparse. We therefore examined patient reported
factors limiting ability to complete planned physiotherapy sessions as well as
limitations for not achieving independency in basic mobility early after hip
fracture surgery. METHODS: A total of 204 consecutive patients with a hip
fracture (mean (SD) age of 80 (9.9) years, 47 patients were admitted from a
nursing home) were treated in accordance with a multimodal program. The Cumulated
Ambulation Score was used to evaluate the patient's independency in three basic
mobility activities: getting in and out of bed, sit-to-stand-to-sit from a chair
and indoor walking. Pre-defined limitations; pain, motor blockade, dizziness,
fatigue, nausea, acute cognitive dysfunction and "other limitations", for not
achieving a full Cumulated Ambulation Score or inability to complete planned
physiotherapy sessions were noted by the physiotherapist on each of the three
first postoperative days. This period was chosen, because of its importance on
how well the patients had regained their pre-fracture functional level. RESULTS:
Fatigue and hip fracture-related pain were the most frequent reasons for patients
not achieving an independent basic mobility level (> 85%) or not fully completing
their planned physiotherapy (> 42%) on all three days. At hospital discharge
(median day 10), only 54% of the patients had regained their pre-fracture basic
mobility level. CONCLUSION: Based on the patient's perception, fatigue and pain
are the most frequent limitations in not achieving independent basic mobility and
not completing physiotherapy after hip fracture surgery. This raises questions
whether multimodal peri-operative programs can be further optimized to enhance
the early recovery of these frail patients. Implications for rehabilitation Early
postoperative mobilization is essential for patients undergoing hip fracture
surgery to regain the pre-fracture functional level, in not only the short but
also in the long term. The most frequent reasons for not achieving an independent
Cumulated Ambulation Score or completing physiotherapy, early after hip fracture
surgery, are fatigue, pain, and the habitual cognitive status of patients.
Knowledge concerning postoperative fatigue is important for rehabilitation
professionals and should contribute as an essential factor when planning
physiotherapy.
PMID- 28415886
TI - Post-operative delayed ambulation after thymectomy is associated withpre
operative six-minute walk distance.
AB - OBJECTIVE: Delayed post-operative ambulation is a risk of post-operative
complications and increases overall healthcare costs. We investigated pre
operative and intraoperative variables associated with delayed ambulation in
patients who underwent thymectomy. METHODS: A total of 57 consecutive patients
undergoing thymectomy were included in this study. Pre-operative functional
exercise capacity was evaluated by six-minute walk distance. Ambulation was
considered to be delayed if the patient could not walk the ward on post-operative
day 1. Binary logistic regression analysis was performed to clarify the factors
associated with delayed ambulation. RESULTS: Pre-operative six-minute walk
distance was the only significant variable that was associated with delayed
ambulation. The area under the receiver operating characteristic curve for
predicting delayed ambulation was 0.684 (95% confidential interval: 0.546-0.823,
p = 0.017), and the optimal discriminatory pre-operative six-minute walk distance
value was 498 m. Post-operative hospital stay was significantly longer in
patients with low six-minute walk distance (<498 m) than those with high six
minute walk distance (>=498 m). In contrast, the presence of myasthenia gravis or
adjuvant chemoradiotherapy was not associated with delayed ambulation.
CONCLUSIONS: Our results suggest that low pre-operative six-minute walk distance
is associated with delayed post-operative ambulation and longer post-operative
hospital stay in patients who underwent thymectomy. Implications for
rehabilitation The predictors for delayed ambulation after thymectomy are not
fully investigated. The presence of myasthenia gravis was not associated with
delayed ambulation. Low pre-operative six-minute walk distance was associated
with delayed ambulation.
PMID- 28415887
TI - Amelioration of late-onset hepatic steatosis in IDH2-deficient mice.
AB - Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general
population and can evolve into nonalcoholic steatohepatosis (NASH), cirrhosis,
and complications such as liver failure and hepatocellular carcinoma. Recently,
we reported that mitochondrial NADP+-dependent isocitrate dehydrogenase, encoded
by the IDH2, plays an important role in the regulation of redox balance and
oxidative stress levels, which are tightly associated with intermediary
metabolism and energy production. In the present study, we showed that in mice
targeted disruption of IDH2 attenuates age-associated hepatic steatosis by the
activation of p38/cJun NH2-terminal kinase (JNK) and p53, presumably induced by
the elevation of mitochondrial reactive oxygen species (ROS), which in turn
resulted in the suppression of hepatic lipogenesis and inflammation via the
upregulation of fibroblast growth factor 21 (FGF21) and the inhibition of
NFkappaB signaling pathways. Our finding uncovers a new mechanism involved in
hepatocellular steatosis and IDH2 may be a valuable therapeutic target for the
management of NAFLD.
PMID- 28415889
TI - Looking beyond the individual: Quality research requires supportive environments.
PMID- 28415888
TI - Bioengineered gold nanoparticles targeted to mesenchymal cells from patients with
bronchiolitis obliterans syndrome does not rise the inflammatory response and can
be safely inhaled by rodents.
AB - The use of gold nanoparticles (GNPs) as drug delivery system represents a
promising issue for diseases without effective pharmacological treatment due to
insufficient local drug accumulation and excessive systemic toxicity.
Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic
lung allograft dysfunction, the main challenge to long-term lung transplantation.
It is believed that due to repeated insults to epithelial bronchiolar cells local
inflammatory response creates a milieu that favors epithelial-mesenchymal
transition and activation of local mesenchymal cells (MCs) leading to airway
fibro-obliteration. In a previous work, we engineered GNPs loaded with the
mammalian target of rapamycin inhibitor everolimus, specifically decorated with
an antibody against CD44, a surface receptor expressed by primary MCs isolated
from bronchoalveolar lavage of BOS patients. We proved in vitro that these GNPs
(GNP-HCe) were able to specifically inhibit primary MCs without affecting the
bronchial epithelial cell. In the present work, we investigated the effect of
these bioengineered nanoconstructs on inflammatory cells, given that a
stimulating effect on macrophages, neutrophils or lymphocytes is strongly
unwanted in graft airways since it would foster fibrogenesis. In addition, we
administered GNP-HCe by the inhalatory route to normal mice for a preliminary
assessment of their pulmonary and peripheral (liver, spleen and kidney) uptake.
By these experiments, an evaluation of tissue toxicity was also performed. The
present study proves that our bioengineered nanotools do not rise an inflammatory
response and, under the tested inhalatory conditions that were used, are non
toxic.
PMID- 28415890
TI - Correction to: Deep genealogical analysis of a large cohort of participants in
the CARTaGENE project (Quebec, Canada).
PMID- 28415891
TI - Influence of two-electrode montages on the level-specific (LS) CE-Chirp auditory
brainstem response (ABR) at multiple intensity levels.
AB - OBJECTIVE: To investigate the influence of two different electrode montages
(ipsilateral: reference to mastoid and vertical: reference to nape of neck) to
the ABR results recorded using a level-specific (LS)-CE-Chirp(r) in normally
hearing subjects at multiple intensities levels. DESIGN: Quasi-experimental and
repeated measure study designs were applied in this study. Two different stopping
criteria were used, (1) a fixed-signal averaging 4000 sweeps and, (2) a minimum
quality indicator of Fmp = 3.1 with a minimum of 800 sweeps. STUDY SAMPLE: Twenty
nine normally hearing adults (18 females, 11 male) participated. RESULTS: Wave V
amplitudes were significantly larger in the LS CE-Chirp(r) recorded from the
vertical montage than the ipsilateral montage. Waves I and III amplitudes were
significantly larger from the ipsilateral LS CE-Chirp(r) than from the other
montages and stimulus combinations. The differences in the quality of the ABR
recording between the vertical and ipsilateral montages were marginal.
CONCLUSIONS: Overall, the result suggested that the vertical LS CE-Chirp(r) ABR
had a high potential for a threshold-seeking application, because it produced a
higher wave V amplitude. The Ipsilateral LS CE-Chirp(r) ABR, on the other hand,
might also have a high potential for the site of lesion application, because it
produced larger waves I and III amplitudes.
PMID- 28415892
TI - Intellectual streaking: The value of teachers exposing minds (and hearts).
AB - As teachers we often ask learners to be vulnerable and yet present ourselves as
high status, knowledgeable experts, often with pre-prepared scripts. This paper
investigates the metaphoric notion of "intellectual streaking" - the nimble
exposure of a teacher's thought processes, dilemmas, or failures - as a way of
modeling both reflection-in-action and resilience. While there is a tension
between credibility and vulnerability, both of which are necessary for trust, we
argue that taking a few risks and revealing deficits in knowledge or performance
can be illuminating and valuable for all parties.
PMID- 28415893
TI - REM sleep deprivation impairs muscle regeneration in rats.
AB - INTRODUCTION: The aim was observe the influence of sleep deprivation (SD) and
sleep recovery on muscle regeneration process in rats submitted to cryolesion.
METHODS: Thirty-two Wistar rats were randomly allocated in four groups: control
(CTL), SD for 96 h (SD96), control plus sleep recovery period (CTL + R) and SD96h
plus 96 h of sleep recovery (SD96 + R). The animals were submitted to muscle
injury by cryolesioning, after to SD and sleep recovery. RESULTS: The major
outcomes of this study were the reduction of muscular IGF-1 in both legs (injured
and uninjured) and a delay in muscle regeneration process of animals submitted to
SD compared to animals that slept, with increase connective tissue, inflammatory
infiltrate and minor muscle fibers. CONCLUSIONS: SD impairs muscle regeneration
in rats, moreover reduces muscular IGF-1 and sleep recovery was able to restore
it to basal levels, but it was not enough to normalize the muscle regeneration.
PMID- 28415894
TI - Should patients be optimistic about surgery? Resolving a conflicted literature.
AB - Following surgery, some patients suffer distress, disappointment, regret, poor
adjustment, and poor quality-of-life. Surgeons may define 'success' based on
objective clinical outcomes, but patients' perceptions of surgical success rely
primarily on a comparison to their initial expectations. We review the literature
on the relationship between patients' surgical expectations and psychosocial
outcomes and attempt to resolve a conflict in the literature. Specifically, we
propose that conflicting conclusions regarding the merits of optimism primarily
stem from differing methodological approaches by researchers in the field.
Studies that examine preoperative expectations in isolation typically conclude
that optimism is positively associated with beneficial psychosocial outcomes.
Studies that compare preoperative expectations to objective surgical outcomes
typically conclude that optimism, particularly unrealistic optimism, is
associated with detrimental psychosocial outcomes. As a whole, the evidence
strongly supports an association between optimistic expectations and positive
psychosocial outcomes following surgery if those expectations are based in
reality. If preoperative optimism ultimately turns out to be unrealistic,
however, it is likely to be a postoperative liability.
PMID- 28415895
TI - The value of liquid biopsy in diagnosis and monitoring of diffuse large b-cell
lymphoma: recent developments and future potential.
AB - INTRODUCTION: Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous
subset of non-Hodgkin lymphomas (NHL) that demonstrate many molecular alterations
and somatic mutations, all of which are targets for the recent development of
biomarkers that use various molecular biological techniques. These non-invasive
emerging biomarkers will be used in the next few years to better monitor the
response to immunochemotherapeutic treatments with the aim of completely
eradicating the disease in order to cure it. Areas covered: In this review, the
authors conducted a literature search to identify and summarize the major
advances in liquid biopsy techniques for DLBCL that are useful for diagnosis and
monitoring minimal residual disease (MRD). The authors report on the major
technological leaps represented by the main MRD tools (sequencing of clone
specific rearrangements of immunoglobulin genes and sequencing of somatic
mutations in circulating tumor plasma DNA) and present the expected future
developments and the impact of these new tools on clinical practice. Expert
commentary: The monitoring of somatic mutations in tumor plasma cell-free DNA
represents a promising tool for liquid biopsy, which will in the future allow non
invasive monitoring that will be used at any time to follow the response to the
treatment.
PMID- 28415896
TI - Multiple mini interviews (MMI): A perspective on the first year of MMI at
Brighton and Sussex Medical School.
AB - Since it was developed at McMaster University School of Medicine in 2002,
multiple medical interviews (MMI) have become a popular and accepted method of
assessing candidates applying for medical training. Unlike a traditional panel
interview it resembles the objective structured clinical examination (OSCE) with
numerous 8-10 min stations assessing different topics or scenarios pertinent to
medical training and healthcare. This was the first year of implementing MMI at
Brighton and Sussex Medical School and my first year of interviewing. I found the
process engaging and thought provoking.
PMID- 28415897
TI - Electric field-navigated transcranial magnetic stimulation for chronic tinnitus:
a randomized, placebo-controlled study.
AB - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may alleviate
tinnitus. We evaluated effects of electric field (E-field) navigated rTMS
targeted according to tinnitus pitch. No controlled studies have investigated
anatomically accurate E-field-rTMS for tinnitus. DESIGN: Effects of E-field-rTMS
were evaluated in a prospective randomised placebo-controlled 6-month follow-up
study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo
targeted to the left auditory cortex corresponding to tonotopic representation of
tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3
and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100)
for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap
Inventory (THI). STUDY SAMPLE: Thirty-nine patients (mean age 50.3 years).
RESULTS: The mean tinnitus intensity (F3 = 15.7, p < 0.0001), annoyance (F3 =
8.8, p = 0.0002), distress (F3 = 9.1, p = 0.0002) and THI scores (F4 = 13.8, p <
0.0001) decreased in both groups over time with non-significant differences
between the groups. After active rTMS, 42% and 37% of the patients showed
excellent response at 1 and 3 months against 15% and 10% in the placebo group (p
= 0.082 and p = 0.065). CONCLUSIONS: Despite the significant effects of rTMS on
tinnitus, differences between active and placebo groups remained non-significant,
due to large placebo-effect and wide inter-individual variation.
PMID- 28415899
TI - Specific muscle synergies in national elite female ice hockey players in response
to unexpected external perturbation.
AB - This study aimed to investigate specific muscle synergies in elite ice hockey
players indicating highly developed postural control strategies used to restore
balance against unexpected external perturbations. Seven elite athletes (EA) on
the women's national ice hockey team and 7 non-athletes (NA) participated in this
study. Based on trajectories of centre of mass (COM), analysis periods were
divided into an initial phase (a balance disturbance after perturbation onset)
and a reversal phase (a balance recovery response), respectively. Muscle
synergies were extracted at each phase by using non-negative matrix
factorization. k-means cluster analysis was performed to arrange similar muscle
synergies in all participants. EA showed significantly shorter recovery period of
COM and smaller body sway than NA. In the initial phase, we identified 2 EA
specific synergies related to ankle plantar flexors or neck extensors. In the
case of an NA-specific synergy, co-activation of the ankle plantar flexors and
dorsiflexors was found. In the reversal phase, no specific muscle synergies were
identified. As the results, EA-specific muscle synergies showed low co-activation
strategy of agonists and antagonists in ankle and neck extensors. Our results
could provide critical information for rehabilitation strategies in athletes
requiring high postural stability.
PMID- 28415898
TI - 31Phosphorus magnetic resonance spectroscopy of the liver for evaluating
inflammation and fibrosis in autoimmune hepatitis.
AB - BACKGROUND: Liver biopsy is the gold standard in evaluating inflammation and
fibrosis in autoimmune hepatitis. AIMS: In search of non-invasive follow-up tools
in autoimmune hepatitis, we evaluated 31phosphorus magnetic resonance
spectroscopy (31P MRS). METHODS: Twelve consecutive AIH patients (mean age 42.8
years, 10 women) underwent liver biopsy, routine laboratory liver function tests,
which were compared to findings in 31P MRS and transient elastography (TE).
RESULTS: Phosphoenolpuryvate (PEP) correlated with the grade of inflammation (r =
0.746, p = .005) and thromboplastin time (r = 0.592, p = .043). It also
differentiated patients with active inflammation from patients without (t =
3.781, p = .009). There was no correlation between PEP and aminotransferase or
immunoglobulin G levels. The phosphoethanolamine (PE)/phosphocholine (PC) ratio,
PE/glyserophosphoethanolamine (GPE) ratio and PC/[total phosphomonoester (PME) +
phosphodiester (PDE)] ratios correlated with immunoglobulin G (r = 0.764, p =
.006; r = 0.618, p = .043; and r= -0.636, p = .035, respectively). PME/PDE and
PE/GPE correlated with fibrosis (r = 0.668, p = .018 and r = 0.604, p = .037).
PE/GPE also differentiated F3 from F0-2 patients (t = 3.810, p = .003).
Phosphorus metabolites did not correlate with TE results and TE did not correlate
with liver histology or laboratory parameters. CONCLUSIONS: 31P MRS seems to
detect active inflammation and advanced fibrosis in AIH patients. TE was
ineffective in fibrosis quantification.
PMID- 28415900
TI - Pediatric nurse practitioners' clinical competencies and knowing patterns in
nursing: Focus group interviews.
AB - BACKGROUND: The generic competency domains of advanced nursing practice have been
reported on in numerous countries, but rather few studies have examined
competencies specific to pediatric nurse practitioners (PNPs). OBJECTIVES: We
identified the core clinical competencies of PNPs in South Korea and related
these identified competencies to the five patterns of knowing in nursing. DESIGN:
Focus group interviews were conducted with five PNP students and four PNPs using
two thematic questions, one on clinical competencies required for PNPs and the
other on competencies specific to Korean PNPs. A purposive sampling method was
used to choose nurses with varying work experience and age from different
hospital units. The inclusion criterion for PNP students was having at least two
years of clinical experience and that for PNPs was having at least two years of
clinical experience as a PNP in pediatric units in tertiary hospitals. The
verbatim transcriptions of these interviews were analysed by two researchers
using inductive content analysis. RESULTS: Six clinical competency domains were
identified including advanced pediatric-specific knowledge and clinical skills,
education and counseling, utilization and engagement in research, professional
identity development, clinical and professional leadership, and holistic care.
Some competencies identified were related to empirical and ethical knowledge that
could be taught in nursing, whereas others were based on esthetic and personal
knowledge, which can be mastered through professional experience. CONCLUSIONS: To
provide holistic care for children and families, PNPs must acquire all necessary
patterns of knowing through continuing education and individual reflection on
personal practice.
PMID- 28415901
TI - Sloping ABR baselines and the ECG myogenic artefact.
AB - OBJECTIVE: To investigate the possibility that a sloping baseline in an ABR
recording has its origins in cardiac activity and if so, identify how it is
expressed. DESIGN: The effect of ECG removal on the averaged ABR was investigated
at two artefact rejection levels. STUDY SAMPLE: Ten 1-minute records of raw EEG
containing ABR responses but contaminated with cardiac activity were recorded
from babies under 12 weeks of age and re-averaged using two artefact rejection
levels. The slope of the ABR recording was measured. The measurements were
repeated after removing effectively the cardiac activity from the records.
RESULTS: A sloping baseline was observed at one or both artefact rejection levels
in all records. The slope varied as the artefact rejection level was changed,
suggesting this may be implicated in slope generation. The slope effectively
disappeared when the cardiac activity was removed from the record. CONCLUSIONS:
Cardiac activity has the potential to cause a sloping ABR baseline. A possible
explanation for this effect is offered, together with suggestions for tester
strategy when a sloping ABR baseline is seen in a clinical setting.
PMID- 28415902
TI - Metabolism studies on hydroxygenkwanin and genkwanin in human liver microsomes by
UHPLC-Q-TOF-MS.
AB - Hydroxygenkwanin (HYGN) and genkwanin (GN) are major constituents of Genkwa Flos
for the treatment of edema, ascites, cough, asthma and cancer. This is a report
about the investigation of the metabolic fate of HYGN and GN in human liver
microsomes and the recombinant UDP-glucuronosyltransferase (UGT) enzymes by using
ultra-performance liquid chromatography quadrupole time-of-flight mass
spectrometry (UHPLC-Q-TOF-MS). An on-line data acquisition method multiple mass
defect filter (MMDF) combined with dynamic background subtraction (DBS) was
developed to trace all probable metabolites. Based on this analytical strategy,
three phase I metabolites and seven glucuronide conjugation metabolites of HYGN,
seven phase I metabolites and 12 glucuronide conjugation metabolites of GN were
identified in the incubation samples of human liver microsomes. The results
indicated that demethylation, hydroxylation and o-glucuronidation were main
metabolic pathways of HYGN and GN. The specific UGT enzymes responsible for HYGN
and GN glucuronidation metabolites were identified using recombinant UGT enzymes.
The results indicated that UGT1A1, UGT1A3, UGT1A9, UGT1A10 and UGT2B7 might play
major roles in the glucuronidation reactions. Overall, this study may be useful
for the investigation of metabolic mechanism of HYGN and GN, and it can provide
reference and evidence for further experiments.
PMID- 28415903
TI - The impact of emotion on numerical estimation: A developmental perspective.
AB - Recent literature has revealed underestimation effects in numerical judgments
when adult participants are presented with emotional stimuli (as opposed to
neutral). Whether these numerical biases emerge early in development however, or
instead reflect overt, learned responses to emotional stimuli across development
are unclear. Moreover, reported links between numerical acuity and mathematics
achievement point to the importance of exploring how numerical approximation
abilities in childhood may be influenced in real-world affective contexts. In
this study, children (aged 6-10 years) and adults were presented with happy and
neutral facial stimuli in the context of a numerical bisection task. Results
reveal that children, like adults, underestimate number following emotional
(i.e., happy) faces (relative to neutral). However, children's, but not adult's,
responses were also significantly more precise following emotional stimuli. In a
second experiment, adult judgments revealed a similar increase in precision
following emotional stimuli when numerical discriminations were more challenging
(involving larger sets). Together, results are the first to reveal children, like
adults, underestimate number in the context of emotional stimuli and this
underestimation bias is accompanied with enhanced response precision.
PMID- 28415904
TI - Wire Atrial Septostomy.
AB - Both balloon atrial septostomy and static balloon dilation are often ineffective
in creating a large atrial septal defect in patients with a thickened atrial
septum. In such situations, blade atrial septostomy and atrial septal stenting
are alternative treatments. We have devised and performed a new technique, called
wire atrial septostomy, which uses a thin soft wire to create a large defect. The
details of the procedure are presented.
PMID- 28415905
TI - Cardiac Perivascular Epithelioid Cell Tumor.
AB - Cardiac tumors presenting as mediastinal masses in childhood are rare. This
report describes the case of a 6-year-old girl who presented to us after a failed
attempt at resection of a mass arising from the left atrial appendage. Computed
tomography-guided biopsy suggested a perivascular epithelioid cell tumor
(PEComa). Sirolimus was started in order to reduce the mass size. She
subsequently underwent resection of the mass by midline sternotomy approach and
cardiopulmonary bypass. Recovery was uneventful and the child is doing well at
two-year follow-up. Contemporary literature is reviewed. Only seven cases,
including two children, with mediastinal PEComa have been reported. Pathology and
treatment options are discussed.
PMID- 28415906
TI - Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium
falciparum and on peritoneal cells of Swiss mice.
AB - CONTEXT: Plants of the Piperaceae family produce piplartine that was used to
synthesize the cinnamides. OBJECTIVE: To assess the effects of piplartine (1) and
cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis,
and peritoneal cells of Swiss mice. MATERIALS AND METHODS: Cultures of Leishmania
amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells
were incubated, in triplicate, with different concentrations of the compounds (0
to 256 MUg/mL). The inhibitory concentration (IC50) in L. amazonensis and
cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method
after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes
was determined by optical microscopy after 48 or 72 h of incubation; the
Selectivity Index (SI) was calculated by CC50/IC50. RESULTS: All compounds
inhibited the growth of microorganisms, being more effective against P.
falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2
MUg/mL) and 5 (IC50 = 6.6 MUg/mL), than to L. amazonensis (compound 1 = 179.0
MUg/mL; compound 5 = 106.0 MUg/mL). Despite all compounds reducing the viability
of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures
of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7)
and 5 (= 38.4). DISCUSSION AND CONCLUSION: The potential of piplartine and
cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical
studies to evaluate their effects in murine malaria and to determine their
mechanisms in cells of the immune system.
PMID- 28415908
TI - The association of personal semantic memory to identity representations: insight
into higher-order networks of autobiographical contents.
AB - Identity representations are higher-order knowledge structures that organise
autobiographical memories on the basis of personality and role-based themes of
one's self-concept. In two experiments, the extent to which different types of
personal semantic content are reflected in these higher-order networks of
memories was investigated. Healthy, young adult participants generated identity
representations that varied in remoteness of formation and verbally reflected on
these themes in an open-ended narrative task. The narrative responses were scored
for retrieval of episodic, experience-near personal semantic and experience-far
(i.e., abstract) personal semantic contents. Results revealed that to reflect on
remotely formed identity representations, experience-far personal semantic
contents were retrieved more than experience-near personal semantic contents. In
contrast, to reflect on recently formed identity representations, experience-near
personal semantic contents were retrieved more than experience-far personal
semantic contents. Although episodic memory contents were retrieved less than
both personal semantic content types to reflect on remotely formed identity
representations, this content type was retrieved at a similar frequency as
experience-far personal semantic content to reflect on recently formed identity
representations. These findings indicate that the association of personal
semantic content to identity representations is robust and related to time since
acquisition of these knowledge structures.
PMID- 28415907
TI - Transdermal oxycodone patch for the treatment of postherpetic neuralgia: a
randomized, double-blind, controlled trial.
AB - AIM: To evaluate the efficacy, systemic exposure, safety and tolerability of a
transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM) in
patients with postherpetic neuralgia (PHN). PATIENTS & METHODS: The study was a
Phase IIa, multicenter, randomized, double-blind, vehicle-controlled crossover
study. RESULTS: While the TPM/oxycodone patch did not significantly improve
'average' Numeric Pain Rating Scale scores versus vehicle patch, patients
reporting high levels of paresthesia (n = 9) showed a trend toward improved pain
reduction. The TPM/oxycodone patch resulted in a low systemic exposure to
oxycodone and was well tolerated. CONCLUSION: The TPM/oxycodone patch delivered
oxycodone to the site of perceived pain in subjects suffering from PHN, but did
not provide analgesia for the broad PHN indication.
PMID- 28415909
TI - Detecting coached neuropsychological dysfunction: a simulation experiment
regarding mild traumatic brain injury.
AB - OBJECTIVE: Performance validity tests (PVTs) and symptom validity tests (SVTs)
are often administered during neuropsychological evaluations. Examinees may be
coached to avoid detection by measures of response validity. Relatively little
research has evaluated whether graduated levels of coaching has differential
effects upon PVT and SVT performance. Accordingly, the present experiment
evaluated the effect of graduated levels of coaching upon the classification
accuracy of commonly used PVTs and SVTs and the currently accepted criterion of
failing two or more PVTs or SVTs. METHOD: Participants simulated symptoms
associated with mild traumatic brain injury (TBI). One group was provided
superficial information concerning cognitive, emotional, and physical symptoms.
Another group was provided detailed information about such symptoms. A third
group was provided detailed information about symptoms and guidance how to evade
detection by PVTs. These groups were compared to an honest-responding group.
Extending prior experiments, stand-alone and embedded PVT measures were
administered in addition to SVTs. RESULTS: The three simulator groups were
readily identified by PVTs and SVTs, but a meaningful minority of those provided
test-taking strategies eluded detection. The Word Memory Test emerged as the most
sensitive indicator of simulated mild TBI symptoms. PVTs achieved more sensitive
detection of simulated head injury status than SVTs. CONCLUSIONS: Individuals
coached to modify test-taking performance were marginally more successful in
eluding detection by PVTs and SVTs than those coached with respect to TBI
symptoms only. When the criterion of failing two or more PVTs or SVTs was
applied, only 5% eluded detection.
PMID- 28415910
TI - Transfer of training in simple addition.
AB - In recent years, several researchers have proposed that skilled adults may solve
single-digit addition problems (e.g., 3 + 1 = 4, 4 + 3 = 7) using a fast counting
procedure. Practicing a procedure often leads to transfer of learning and faster
performance of unpracticed items. Such transfer has been demonstrated using a
counting-based alphabet arithmetic task (e.g., B + 4 = C D E F) that indicated
robust generalization of practice (i.e., response time [RT] gains) when untrained
transfer problems at test had been implicitly practiced (e.g., practice B + 3,
test B + 2 or B + 1). Here, we constructed analogous simple addition problems
(practice 4 + 3, test 4 + 2 or 4 + 1). In each of three experiments (total n =
108), participants received six practice blocks followed by two test blocks of
new problems to examine generalization effects. Practice of addition identity
rule problems (i.e., 0 + N = N) showed complete transfer of RT gains made
during practice to unpracticed items at test. In contrast, the addition ties (2 +
2, 3 + 3, etc.) presented large RT costs for unpracticed problems at test, but
sped up substantially in the second test block. This pattern is consistent with
item-specific strengthening of associative memory. The critical items were small
non-tie additions (sum <= 10) for which the test problems would be implicitly
practiced if counting was employed during practice. In all three experiments (and
collectively), there was no evidence of generalization for these items in the
first test block, but there was robust speed up when the items were repeated in
the second test block. Thus, there was no evidence of the generalization of
practice that would be expected if counting procedures mediated our participants'
performance on small non-tie addition problems.
PMID- 28415911
TI - Risk, safety and sex among male PrEP users: time for a new understanding.
AB - Recent advances in biomedical HIV prevention have led to optimistic projections
of a dramatic worldwide reduction of new infections by 2030. This optimism is
counterbalanced by concerns that the protective benefits of one such technology,
HIV pre-exposure prophylaxis (PrEP), may be negated by increases in other
behaviours that offset these benefits (risk compensation). To contribute to a
deeper understanding of concepts of safety and risk in the context of HIV PrEP,
we draw on the narrative accounts of 61 male PrEP users who participated in the
inaugural PrEP demonstration project: the iPrEx open-label extension study. We
conducted in-depth interviews with a purposeful sample of iPrEx participants.
Overall, participants did not report significant changes to their sexual
practices once they had begun taking PrEP. Rather, participants reported
experiencing a sense of relief or reprieve from HIV-related stress. This
unburdening of fear did not necessarily lead to condomless sex. Instead, men
expressed feeling a sense of security and less free-floating fear of HIV. We
contend that no longer living under the threat of HIV is a significant benefit
that has not been adequately explored in HIV prevention research.
PMID- 28415912
TI - A Method for the Immunohistochemical Identification and Localization of Osterix
in Periosteum-Wrapped Constructs for Tissue Engineering of Bone.
AB - A novel immunohistochemistry (IHC) approach has been developed to label and
localize osterix, a bone-specific transcription factor, within formalin-fixed,
paraffin-embedded, tissue-engineered constructs uniquely containing synthetic
polymers and human periosteal tissue. Generally, such specimens consisting in
part of polymeric materials and mineral are particularly difficult for IHC
identification of proteins. Samples here were fabricated from human periosteum,
electrospun poly-l-lactic acid (PLLA) nanofibers, and polycaprolactone/poly-l
lactic acid (PCL/PLLA, 75/25) scaffolds and harvested following 10 weeks of
implantation in athymic mice. Heat-induced and protease-induced epitope retrieval
methods from selected existing protocols were examined to identify osterix. All
such protease-induced techniques were unsuccessful. Heat-induced retrieval gave
positive results for osterix immunohistochemical staining in sodium
citrate/EDTA/Tween 20 with high heat (120C) and pressure (~30 psi) for 10 min,
but the heat and pressure levels resulted in tissue damage and section
delamination from slides that limited protocol effectiveness. Heat-induced
epitope retrieval led to other osterix-positive staining results achieved with
minimal impact on structural integrity of the tissue and polymers in sodium
citrate/EDTA/Tween 20 buffer at 60C and normal pressure (14.5 psi) for 72 hr. The
latter approach identified osterix-positive cells by IHC within periosteal
tissue, layers of electrospun PLLA nanofibers, and underlying PCL/PLLA scaffolds
of the tissue-engineered constructs.
PMID- 28415913
TI - Characteristics and management of primary and other immune thrombocytopenias:
Spanish registry study.
AB - BACKGROUND: The natural history and its modulation by treatments administered for
immune thrombocytopenia (ITP) in the clinical practice remains unknown. In
addition, little information is available on the characteristics and management
of ITP in Spain. METHODS: We conducted an observational, multicenter, registry in
70 Hematology Services from Spain between 2009 and 2011, which included children
from 2 months of age and adults with primary ITP or another ITP diagnosed within
the last 6 months (platelet count [PC] < 100 * 109/l). Patients were followed-up
at 6 and 12 months. RESULTS: 484 patients were included (median [Q1, Q3] age 52
[29,74] years, 87.6% adults), 56% women, 10.5% with secondary ITP. Median (Q1,
Q3) PC at diagnosis was 12 * 109/l (4, 32); 72% of patients had bleeding symptoms
(62% cutaneous bleeding, 29% oral cavity bleeding, 18% epistaxis). 81% of
patients with primary ITP received first-line treatment, mainly with
corticosteroids (>6 weeks in 59% of cases), either alone (41%) or associated with
intravenous immunoglobulin (33%). The response (>=30 * 109/L) to first-line
treatment was 92%. A total of 19% of patients received second-line treatment and
6% additional treatments. At 12 months, 74% of primary ITP patients maintained a
PC >= 100 * 109/L in absence of treatment (10% still had hemorrhagic
manifestations). CONCLUSIONS: Characteristics of Spanish ITP patients are
comparable to those from other countries. Although a high response rate to first
line treatments is observed, at 1 year, the disease persists in around one
quarter of patients. Overall therapeutic management in Spain conforms to current
recommendations, except for an excessive duration of corticosteroids therapy.
PMID- 28415914
TI - Sealing of the round and oval window niches with triamcinolone-soaked fascia as
salvage surgical therapy in sudden sensorineural hearing loss.
AB - CONCLUSIONS: Triamcinolone-soaked fascia seems to show better hearing improvement
when added to tympanotomy for sudden idiopathic sensorineural hearing loss
(SSHL), compared to fascia round window occlusion without triamcinolone.
OBJECTIVES: To analyse if adding triamcinolone to sealing the round and oval
window niches with fascia results in improved audiological outcome for acute
SNHL. METHODS: Fifty-three patients (27m:43 +/- 12 years, 26f:45 +/- 14 years)
with acute SSHL >=50dB over 3 frequencies, who failed primary therapy, underwent
transcanal tympanotomy. Twenty-five patients (Group A;cortisone:14m, 11f:46 +/- 9
years) received sealing of the round and oval window with fascia soaked in
triamcinolone (1ml; 40mg/ml) and 28 controls (Group B;no-cortisone:13m, 15f, 42
+/- 12 years) without triamcinolone. Frequency specific and pure tone average
(PTA =500-1000-2000-3000Hz) results were compared between Group A and B pre- and
postoperatively. RESULTS: In Group A the PTA improved by >=10dB in 21/25(83%)
cases; in Group B 18/28(63%). Group A showed a statistically significantly better
improvement across all frequencies, while linear regression revealed a
significant decrease of posttherapeutic PTA to 94.96% of the initial PTA (p =
.037). The overall PTA improved by 24dB. Group A improved from 73dB to 41dB(
32dB) PTA, Group B improved from 76dB to 56dB PTA (-20dB) (p < .05). Group A
showed a significant additional decrease of 12.8dB (p < .001).
PMID- 28415915
TI - Evaluation of dogs with macroscopic haematuria: a retrospective study of 162
cases (2003-2010).
AB - AIMS: To retrospectively describe clinical features of dogs that were presented
to a small animal clinic between 2003-10 with macroscopic haematuria, and
investigate whether signalment of the dog and severity and duration of the
haematuria at admission were associated with specific aetiologies. METHODS:
Medical records were evaluated of 162 dogs with macroscopic haematuria admitted
to a University-based small animal clinic in Thessaloniki, Greece, from January
2003 to December 2010. The inclusion criteria were discolouration of the urine
sediment combined with abnormal numbers of erythrocytes, when examined
microscopically. Data collected from the medical records included signalment,
severity, frequency and duration of haematuria, and diagnosis. RESULTS: Between
January 2007 and December 2010, 8,893 dogs were admitted to the clinic; of these
99 (1.1%) were admitted with haematuria. Of the 162 dogs with records of
haematuria, 80 (49.4%) were aged between 5.1-10 years, presented with acute
(96/162; 59.3%), constant (99/162; 61.1%) and mild/moderate (150/162; 92.6%)
haematuria. Of 147 dogs with a recorded diagnosis, the commonest diagnoses were
urinary tract infection (UTI, 42/147; 28.6%), urolithiasis (38/147; 25.9%),
prostatic disease (25/147; 17.0%) and urinary tumours (13/147; 8.8%). The
prevalence of UTI was higher in female (22/56; 39%) than male (20/91; 22%) dogs,
and in medium sized (22/52; 42%) than small (6/40; 15%) dogs. Urolithiasis was
most prevalent in small (21/40; 52.5%) dogs, and all dogs with urolithiasis
presented with mild/moderate haematuria. The prevalence of prostatic disease was
highest in large (11/46; 24%) and giant (3/9; 33%) sized dogs and in dogs aged
>10 years (8/30; 27%). CONCLUSIONS AND CLINICAL RELEVANCE: In this retrospective
study from one small animal clinic, UTI, urolithiasis, prostatic disease and
urinary tumours predominated among the causes of canine haematuria. The
consideration of sex, age, and size of the dog and characteristics of haematuria
were found to be useful parameters when forming the list of differential
diagnoses.
PMID- 28415916
TI - Association between psychosocial stress and hypertension: a systematic review and
meta-analysis.
AB - AIM: The etiology of hypertension is various and complex, involving both genetic
and behavioral factors. The relationship between psychosocial stress and
hypertension has been hypothesized. More and more people experience increased
anxiety, depression, and chronic psychosocial stress brought on by globalization,
cultural changes, socioeconomic changes, and stress at the work place. Although a
plethora of studies have investigated the interaction between psychosocial stress
and hypertension, this relationship is still contentious. The objective of this
study is twofold. First, a review of recent advancements in our understanding of
the relationship between psychosocial stress and hypertension. Second, a meta
analysis aiming to assess the relationship between chronic psychosocial stress
and blood pressure. METHODS: We systematically searched and identified relevant
studies from five databases, including PubMed, Cochrane Library, China National
Knowledge Infrastructure (CNKI), CQVIP, and the Wanfang Database until April
2016. Eleven studies encompassing 5696 participants were included in the final
analysis. RESULTS: Data showed that psychosocial stress was associated with an
increased risk of hypertension (OR = 2.40, 95% CI = 1.65-3.49), and hypertensive
patients had a higher incidence of psychosocial stress compared to normotension
patients (OR = 2.69, 95% CI = 2.32-3.11). Based on our meta-analysis, chronic
psychosocial stress may be a risk factor for hypertension. CONCLUSION: The few
cohort and case-control studies on the association between psychosocial stress
and hypertension employed variable definition of stressors and the responses,
making the meta-analysis difficult. Although we found an association between
chronic psychosocial stress and hypertension, more studies are needed to confirm
this relationship.
PMID- 28415917
TI - Exercise rehabilitation immediately following ischemic stroke exacerbates
inflammatory injury.
AB - OBJECTIVES: The rehabilitative benefits of physical exercise after stroke appear
to be contingent upon exercise initiation timing. The present study assessed the
hypothesis that very early post-stroke exercise would amplify cellular stress and
increases expression of pro-inflammatory mediators, while exercise initiated
later would limit the inflammation associated with cerebral ischemia/reperfusion
injury. METHODS: Adult rats were subjected to middle cerebral artery occlusion
and subsequently assigned to one of seven groups: one sham injury control group,
three stroke groups subjected to exercise initiated after 6, 24 hours, or 3 days
of reperfusion, and three stroke groups not subjected to exercise. Expression of
intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM
1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta)
were examined 3 and 24 hours after completion of exercise regimens (and at
corresponding time points in non-exercise controls). Heat shock protein-70
(Hsp70) and hypoxia inducible factor-1alpha (HIF-1alpha) expression levels were
also compared between exercise and non-exercise groups. RESULTS: Early post
stroke exercise was associated with increased expression of pro-inflammatory
mediators (ICAM-1, VCAM-1, TNF-alpha, and IL-1beta) and increased expression of
cell stress markers (Hsp70 and HIF-1alpha). Exercise initiated after 3 days of
reperfusion was associated with decreased expression of these molecules.
CONCLUSION: Post-stroke exercise, if too early, may result in elevated levels of
cell stress and increased expression of pro-inflammatory cytokines, which may
amplify the tissue damage associated with cerebral ischemia/reperfusion injury.
The results shed light on the manner in which exercise initiation timing may
affect post-stroke rehabilitation.
PMID- 28415918
TI - Financial Difficulty: A Barrier to Self-care in Patients With Diabetes.
PMID- 28415920
TI - What can the food and drink industry do to help achieve the 5% free sugars goal?
AB - AIMS: To contribute evidence and make recommendations to assist in achieving free
sugars reduction, with due consideration to the broader picture of weight
management and dietary quality. METHODS: An expert workshop in July 2016
addressed options outlined in the Public Health England report 'Sugar reduction:
The evidence for action' that related directly to the food industry. Panel
members contributed expertise in food technology, public heath nutrition,
marketing, communications, psychology and behaviour. Recommendations were
directed towards reformulation, reduced portion sizes, labelling and consumer
education. These were evaluated based on their feasibility, likely consumer
acceptability, efficacy and cost. RESULTS: The panel agreed that the 5% target
for energy from free sugars is unlikely to be achievable by the UK population in
the near future, but a gradual reduction from average current level of intake is
feasible. Progress requires collaborations between government, food industry, non
government organisations, health professionals, educators and consumers.
Reformulation should start with the main contributors of free sugars in the diet,
prioritising those products high in free sugars and relatively low in
micronutrients. There is most potential for replacing free sugars in beverages
using high-potency sweeteners and possibly via gradual reduction in sweetness
levels. However, reformulation alone, with its inherent practical difficulties,
will not achieve the desired reduction in free sugars. Food manufacturers and the
out-of-home sector can help consumers by providing smaller portions. Labelling of
free sugars would extend choice and encourage reformulation; however, government
needs to assist industry by addressing current analytical and regulatory
problems. There are also opportunities for multi-agency collaboration to develop
tools/communications based on the Eatwell Guide, to help consumers understand the
principles of a varied, healthy, balanced diet. CONCLUSION: Multiple strategies
will be required to achieve a reduction in free sugars intake to attain the 5%
energy target. The panel produced consensus statements with recommendations as to
how this might be achieved.
PMID- 28415921
TI - Intimate strangers: Eritrean male asylum seekers' perceptions of marriage and
sexuality.
AB - This study examined perceptions of marriage and sexuality among male asylum
seekers from Eritrea. Semi-structured in-depth interviews were conducted with 14
men living in Israel. Their perceptions of marriage and sexuality were found to
be influenced by their life as asylum seekers, and particularly by their
encounter with a different culture, by their lack of legal status, and by the
marked numerical imbalance between women and men within their community. Changes
in their perceptions occurred after their arrival in Israel, and included greater
relaxing of social codes and the transition from a relatively 'closed' sexual
mindset to a more 'open' one. It is important to understand how lack of status
affects male asylum seekers' intimate relationships with women, and to recognise
such men as subjects with legitimate sexual and partnering needs, thereby
broadening existing discourse in this field, which tends to present male asylum
seekers primarily as sources of cheap labour and as sexual Others.
PMID- 28415922
TI - Host pharmacokinetics and drug accumulation of anthelmintics within target
helminth parasites of ruminants.
AB - Anthelmintic drugs require effective concentrations to be attained at the site of
parasite location for a certain period to assure their efficacy. The processes of
absorption, distribution, metabolism and excretion (pharmacokinetic phase)
directly influence drug concentrations attained at the site of action and the
resultant pharmacological effect. The aim of the current review article was to
provide an overview of the relationship between the pharmacokinetic features of
different anthelmintic drugs, their availability in host tissues, accumulation
within target helminths and resulting therapeutic efficacy. It focuses on the
anthelmintics used in cattle and sheep for which published information on the
overall topic is available; benzimidazoles, macrocyclic lactones and monepantel.
Physicochemical properties, such as water solubility and dissolution rate,
determine the ability of anthelmintic compounds to accumulate in the target
parasites and consequently final clinical efficacy. The transcuticular absorption
process is the main route of penetration for different drugs in nematodes and
cestodes. However, oral ingestion is a main route of drug entry into adult liver
flukes. Among other factors, the route of administration may substantially affect
the pharmacokinetic behaviour of anthelmintic molecules and modify their
efficacy. Oral administration improves drug efficacy against nematodes located in
the gastroinestinal tract especially if parasites have a reduced susceptibility.
Partitioning of the drug between gastrointestinal contents, mucosal tissue and
the target parasite is important to enhance the drug exposure of the nematodes
located in the lumen of the abomasum and/or small intestine. On the other hand,
large inter-animal variability in drug exposure and subsequent high variability
in efficacy is observed after topical administration of anthelmintic compounds.
As it has been extensively demonstrated under experimental and field conditions,
understanding pharmacokinetic behaviour and identification of different factors
affecting drug activity is important for achieving optimal parasite control and
avoiding selection for drug resistance. The search for novel alternatives to
deliver enhanced drug concentrations within target helminth parasites may
contribute to avoiding misuse, and prolong the lifespan of existing and novel
anthelmintic compounds in the veterinary pharmaceutical market.
PMID- 28415923
TI - Hand grip strength determination for healthy males in Saudi Arabia: A study of
the relationship with age, body mass index, hand length and forearm circumference
using a hand-held dynamometer.
AB - Objectives To determine whether age, body mass index (BMI), hand length and
forearm circumference were predictive of hand grip strength in healthy Saudi
Arabian adult males. Methods This cross-sectional descriptive study recruited
healthy adult male volunteers. Their anthropometric characteristics including
age, BMI, hand length and forearm circumference were measured using routine
techniques. Hand grip strength was assessed using a Jamar(r) Hydraulic Hand
Dynamometer. The data were analysed using Pearson correlation coefficient ( r) as
well as by a stepwise multiple linear regression analysis. Results The study
included 116 healthy males who satisfied the inclusion criteria. A Pearson
correlation coefficient matrix demonstrated that all the four measures, age, BMI,
hand length and forearm circumference, were significantly correlated with hand
grip strength. Age had an inverse correlation with hand grip strength. The
anthropometric measures of hand length, age and forearm circumference accounted
for 44.2% (R2 0.442) of the variation of the hand grip strength. Conclusion Hand
length, age and forearm circumference significantly impacted on hand grip
strength in Saudi Arabian healthy adult males.
PMID- 28415924
TI - An assessment of the current treatment landscape for rheumatology patients in
Qatar: Recognising unmet needs and moving towards solutions.
AB - Objective This study assessed the mode of application (oral, intravenous or
subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis
(RA) in patients from Qatar in comparison with patients' individual preferences
for the mode of application of their treatment. Methods This study included 294
RA patients visiting three clinics at the main referral hospital in Qatar who
were interviewed using a standard questionnaire to determine their preference of
mode of application for their disease-modifying antirheumatic drug (DMARD)
treatment in relation to their currently employed mode of application. Results
The majority of patients were female (76%), and 93% of male patients and 61% of
female patients in the study clinics were of a nationality other than Qatari. The
highest patient preference recorded was for an oral therapy (69%), compared with
injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed
a preference to remain on oral therapy compared with 63% and 58% of intravenous
and SC injection patients indicating a preference to remain on their current
method of administration. Conclusions This high preference for oral therapies
highlights the considerable need for incorporation of new oral targeted synthetic
DMARD therapies into clinical practice within the region.
PMID- 28415926
TI - Urban and rural stroke mortality rates in China between 1988 and 2013: An age
period-cohort analysis.
AB - Objective To evaluate effects attributable to age, time period and birth cohort,
on stroke mortality data from urban and rural regions in China between 1988 and
2013. Methods Mortality data were obtained from the Chinese Health Statistics
Annual Report (1987-2001) and Chinese Health Statistics Yearbooks (2003-2014).
Population data were obtained from population censuses (i.e. 1982, 1990, 2000 and
2010). Data were analysed using an age-period-cohort (APC) model and intrinsic
estimation (IE) method. Results The age effect suggested that all older residents
had higher stroke mortality risk than younger residents. Period effect showed
that compared with figures for 1988, stroke mortality in 2013 was 1.8 times
higher for urban regions and 2.4 times higher for rural regions. After
controlling for age and period effects, cohorts born before the Chinese economic
reform had a steady decline in stroke mortality. However, mortality rates
increased and fluctuated in post-reform cohorts. Conclusions This APC-IE analysis
identified a modest period effect with large age and cohort contributions to both
the overall mortality and the disparity between urban and rural stroke mortality.
Identifying early life and cumulative risk factors for stroke, improving equality
in stroke prevention and care are needed to reduce the stroke mortality in China.
PMID- 28415927
TI - Transarterial embolization for renal angiomyolipomas: A single centre experience
in 79 patients.
AB - Objective To evaluate the long-term efficacy and safety of selective arterial
embolization (SAE) in the treatment of renal angiomyolipomas (AMLs). Methods This
was a retrospective review of medical records and imaging findings from patients
with renal AMLs who attended our clinic and received SAE between January 2007 and
January 2014. Only patents with complete medical records, preoperative computed
tomography scans using typical imaging and follow-up data were included. Results
A total of 79 patients were enrolled in the study. Technical and clinical success
rates were 100% and 91% ( n = 72), respectively. Only two patients experienced
major complications. Post-embolization syndrome (i.e. fever, abdominal pain,
nausea or vomiting) was reported in 68 (86%) patients, but all symptoms were mild
and resolved with conservative measures. Mean radiological and clinical follow-up
periods were 16.8 and 35.9 months, respectively. In 75 (95%) patients, tumours
decreased in size; mean +/- SD tumour size significantly decreased from 8.4 +/-
3.5 cm pre-embolization to 6.7 +/- 3.0 cm post-embolization . Conclusions This
study provides long-term evidence that SAE is a safe and effective method in the
treatment of patients with renal AMLs.
PMID- 28415928
TI - Incidence and risk factors for rectal pain after laparoscopic rectal cancer
surgery.
AB - Objective This study was performed to investigate the incidence of and potential
risk factors for rectal pain after laparoscopic rectal cancer surgery. Methods We
retrospectively analyzed data from 300 patients who underwent laparoscopic rectal
cancer surgery. We assessed the presence of rectal pain and categorized patients
into Group N (no rectal pain) or Group P (rectal pain). Results In total, 288
patients were included. Of these patients, 39 (13.5%) reported rectal pain and 14
(4.9%) had rectal pain that persisted for >3 months. Univariate analysis revealed
that patients in Group P had more preoperative chemoradiotherapy, more
ileostomies, longer operation times, more anastomotic margins of <2 cm from the
anal verge, more anastomotic leakage, and longer hospital stays. Multivariate
analysis identified an anastomotic margin of <2 cm from the anal verge and a long
operation time as risk factors. The presence of diabetes mellitus was a negative
predictor of rectal pain. Conclusions In this study, the incidence of rectal pain
after laparoscopic rectal cancer surgery was 13.5%. An anastomotic margin of <2
cm from the anal verge and a long operation time were risk factors for rectal
pain. The presence of diabetes mellitus was a negative predictor of rectal pain.
Thus, the possibility of postoperative rectal pain should be discussed
preoperatively with patients with these risk factors.
PMID- 28415929
TI - Retrospective analysis of a surgical innovation using the IDEAL framework:
radical cystectomy with epidural anaesthesia.
AB - Objectives To retrospectively analyse experience of radical cystectomy using
spinal/epidural anaesthesia and to classify this method using the IDEAL criteria.
Methods Data from patients who had undergone radical cystectomy using
spinal/epidural anaesthesia were evaluated retrospectively, focusing on clinical
data, intraoperative and perioperative parameters and postoperative
complications. Current literature reporting on this technique was reviewed and,
together with the present study, evaluated according to the IDEAL
recommendations. Results Three male patients aged 66-79 years who had undergone
radical cystectomy with epidural anaesthesia were identified. The operating time
ranged from 159-261 min and only minor complications occurred. Between 2013 and
2015, three published studies reported experiences with radical cystectomy with
epidural/spinal anaesthesia; one was prospective and two were retrospective in
nature and they included a total of 55 patients. According to the IDEAL
classification, the present study corresponds to stage 1 (idea) and overall the
surgical technique can be ranked as stage 2a (development). Conclusions Radical
cystectomy with epidural anaesthesia is feasible and applicable for those who are
not fit for general anaesthesia. The present study confirmed the functional
results of this technique, which can be classified as IDEAL stage 2a on the basis
of published studies.
PMID- 28415925
TI - The role of oxidative stress, inflammation and acetaminophen exposure from birth
to early childhood in the induction of autism.
AB - The wide range of factors associated with the induction of autism is invariably
linked with either inflammation or oxidative stress, and sometimes both. The use
of acetaminophen in babies and young children may be much more strongly
associated with autism than its use during pregnancy, perhaps because of well
known deficiencies in the metabolic breakdown of pharmaceuticals during early
development. Thus, one explanation for the increased prevalence of autism is that
increased exposure to acetaminophen, exacerbated by inflammation and oxidative
stress, is neurotoxic in babies and small children. This view mandates extreme
urgency in probing the long-term effects of acetaminophen use in babies and the
possibility that many cases of infantile autism may actually be induced by
acetaminophen exposure shortly after birth.
PMID- 28415931
TI - Comparison of dexmedetomidine and propofol for conscious sedation in inguinal
hernia repair: A prospective, randomized, controlled trial.
AB - Objective The ideal agents for conscious sedation during ambulatory inguinal
hernia repair are still unclear. We aimed to compare the analgesic, sedative,
haemodynamic, and side effects of dexmedetomidine with those of propofol in
combination with fentanyl for conscious sedation in patients undergoing inguinal
hernia repair. Methods Eighty patients undergoing unilateral inguinal hernia
repair were prospectively randomized to receive either dexmedetomidine (n = 40)
or propofol (n = 40). Dexmedetomidine and propofol dosages were adjusted to
maintain the targeted level of sedation. Results After administration of sedative
drugs, patients who received dexmedetomidine had a significantly lower heart
rate. The intraoperative requirement of fentanyl was significantly lower in
patients who received dexmedetomidine compared with patients who received
propofol. Administration of dexmedetomidine was associated with a reduced
postoperative pain score, longer time for onset of sedation, and a slightly
longer recovery time. No serious adverse events occurred in either group. The
patients' overall satisfaction score was comparable between the two groups.
Conclusion Dexmedetomidine is an effective adjuvant when co-administered with
fentanyl for conscious sedation in patients who undergo inguinal hernia repair.
Administration of dexmedetomidine decreases the requirement of fentanyl and the
pain score, but slightly prolongs the time to sedation and recovery.
PMID- 28415930
TI - Computed tomography-guided transthoracic biopsy: Factors influencing diagnostic
and complication rates.
AB - Objective This study was performed to assess the complication and diagnostic
rates of computed tomography (CT)-guided transthoracic needle biopsy of pulmonary
parenchymal and mediastinal lesions. Methods Patients who were suspected to have
a malignancy based on chest imaging and CT and could not be otherwise diagnosed
were evaluated. Results Sixty-five patients were included; 48 (73.8%) were male
and 17 (26.2%) were female. Their average age was 58 years. The lesion size
ranged from 11 to 105 mm. The most common specific histologic subtype was
adenocarcinoma, and the least common was lymphoma. The diagnostic rate was 90.8%.
The mean complication rate was 15.4%. Statistically significant associations were
found between the complication rate and needle size and between the needle path
length and lesion size. Conclusion CT-guided needle biopsy is an effective
diagnostic method for patients with mediastinal and parenchymal lesions before
thoracotomy. This method can also reliably differentiate benign and malignant
tumors.
PMID- 28415932
TI - The effects of corrective surgery on endothelial biomarkers and anthropometric
data in children with congenital heart disease.
AB - Objective To investigate the influence of surgical correction on biomarkers of
endothelial dysfunction in children with congenital heart disease and to evaluate
anthropometric data. Methods Children with pulmonary hypertension (PH) or
Tetralogy of Fallot (TOF) who were scheduled for corrective surgery were enrolled
in this prospective study. Age-matched healthy children were included as
controls. Demographic, haemodynamic and cardiac ultrasonography data were
collected. Blood samples were taken pre-surgery, 24-48 hours post-surgery and
again 3-6 months later. Several biomarkers (protein C, soluble platelet selectin
[CD62P], soluble endothelium selectin [CD62E], soluble leukocyte selectin
[CD62L], plasma von Willebrand Factor [vWF] atrial natriuretic peptide [ANP],
brain natriuretic peptide[(BNP] and insulin-like growth factor-1 [IGF-1]) were
measured. Results Sixty-three children (32 with PH, 15 with TOF, and 16 controls)
were enrolled. No significant differences between the PH and TOF groups were
observed in the expression of biomarkers pre- and post-surgery. IGF-1 levels were
closely related to anthropometric data, particularly those children with PH.
Expression of IGF-1 and weight/height normalized after corrective surgery.
Conclusions No significant endothelial dysfunction was observed in children with
PH or TOF before or after corrective surgery. Significant retardation of growth,
particularly weight, was found before surgery and may be related to IGF-1
suppression.
PMID- 28415933
TI - Incidence, risk factors and the effect of polyomavirus infection in hematopoietic
stem cell transplant recipients.
AB - Objective The effect of polyomavirus infection in HSCT recipients is poorly
understood. Methods We evaluated 38 HSCT recipients. Polyomavirus was detected by
nested qualitative polymerase chain reaction (PCR) assays of urine. The risk
factors for BK virus and JC virus were analysed. The kidney and liver functions
of infected and uninfected patients were compared. Results BK virus, JC virus,
and simian virus 40 were detected in 21%, 42%, and 0% of HSCT recipients
respectively. HCMV infection was found to be an independent risk factor for JC
virus infection (odds ratio (OR): 8.528), while transplants with mismatched HLA
are more susceptible to BK virus infection (OR: 12.000). Liver function of JC
virus-infected subjects was worse than that of uninfected subjects. Conclusion We
must be vigilant for opportunistic polyomavirus infections in HSCT recipients,
especially those with HCMV co-infection or a mismatched HLA transplant. When
unexplained liver function deterioration is observed, JC virus infection should
be considered.
PMID- 28415934
TI - Early abnormal liver enzyme levels may increase the prevalence of human
cytomegalovirus antigenaemia after hematopoietic stem cell transplantation.
AB - Objective Human cytomegalovirus (HCMV) infection is common after bone marrow
transplantation (BMT), and it increases morbidity and mortality for transplant
recipients. HCMV infection may cause hepatitis and elevate the liver enzymes
aspartate transferase (AST) and alanine transferase (ALT). This study aimed to
analyse the associations between liver enzyme levels and infection with HCMV
antigenaemia after BMT. Methods Data from 30 patients after BMT were collected at
different time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 months
post-transplantation). The patients were divided into the HCMV antigenaemia
positive and HCMV antigenaemia-negative groups according to a peripheral blood
pp65 antigen assay. Immunohistochemistry was used to identify HCMV pp65 antigen
and conventional methods were used to detect liver enzyme levels. Results Twelve
patients were pp65 antigenaemia-positive and 10 patients were positive in the
first 3 months post-transplant. Liver enzyme levels were increased after
positivity for HCMV antigenaemia (p = 0.034 and p = 0.018 for ALT and AST,
respectively). One month before antigenaemia, AST levels were higher in the HCMV
antigenaemia-positive group compared with the negative group (p = 0.006).
Conclusion HCMV antigenaemia mostly occurs in the early stage of post-BMT and
early abnormal liver enzyme levels may increase the chance of HCMV antigenaemia
after BMT.
PMID- 28415935
TI - Naringenin improves the healing process of thermally-induced skin damage in rats.
AB - Objective To evaluate the effect of the phenolic compound naringenin on thermal
burn-induced inflammatory responses and oxidative stress in rats. Methods First
degree thermal burn injuries were induced in shaved rats by 10 s immersion of the
back surface in water at 90C. Naringenin treatment (25, 50 and 100 mg/kg/day) was
initiated 24 h following burn injury, and continued for 7 days. On treatment day
7, serum tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, nitric
oxide (NO), prostaglandin (PG)E2, caspase-3, leukotriene (LT)-B4 and nuclear
factor (NF)-kappaB levels were quantified. Skin sample glutathione (GSH) and
thiobarbituric acid reactive substances (TBARS) levels, and catalase, superoxide
dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx)
activities, were also measured. Results Serum inflammatory biomarkers were
significantly increased in thermal-burn injured rats versus uninjured controls.
Naringenin significantly inhibited the increased proinflammatory markers at day 7
of treatment. Increased TBARS levels and decreased GSH levels in wounded skin
were significantly restored by naringenin treatment at day 7. SOD, catalase, GPx
and GST activities were markedly inhibited in wounded skin tissues, and were
significantly increased in naringenin-treated rats. Conclusion Naringenin
treatment showed anti-inflammatory and antioxidant effects in rats with thermal
burn-induced injury.
PMID- 28415936
TI - Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors:
National Health and Nutrition Examination Survey (NHANES) 1999-2010.
AB - Objectives To determine whether the associations with key risk factors in
patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are
different using data from the National Health and Nutrition Examination Survey
(NHANES) from 1999 to 2010. Methods The study analysed the prevalence and
association with risk factors of undiagnosed and diagnosed T2DM using a
regression model and a multinomial logistic regression model. Data from the
NHANES 1999-2010 were used for the analyses. Results The study analysed data from
10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM
increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was
significantly higher in non-Hispanic whites, in individuals <30 years old and in
those with near optimal (130-159 mg/dl) or very high (>=220 mg/dl) non-high
density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass
index, low economic status or low educational level had no effect on T2DM
diagnosis rates. Though diagnosed T2DM was associated with favourable
diet/carbohydrate intake behavioural changes, it had no effect on physical
activity levels. Conclusion The overall T2DM prevalence increased between 1999
and 2010, particularly for undiagnosed T2DM in patients that were formerly
classified as low risk.
PMID- 28415937
TI - Heparinized saline versus normal saline for maintaining peripheral venous
catheter patency in China: An open-label, randomized controlled study.
AB - Objective To evaluate the effects of heparin saline versus normal saline as
locking solution for maintaining patency in peripheral venous catheters in
Chinese patients. Methods This open-label, randomized controlled study was
conducted in two hepatobiliary surgery wards, where patients received identical
treatments, at a tertiary referral hospital. Patients were randomly divided into
a normal saline group (NS, 3 ml) or a heparin saline group (HS, 50 IU/ml, 3 ml)
for catheter sealing. Results The study enrolled 286 patients and 609 peripheral
venous catheters were included in the analysis. The patients in the two groups
had no local infections or catheter-related bloodstream infections. There were no
significant differences between the two groups in terms of the rate of catheter
obstruction, duration time, or the rates of phlebitis, infiltration, and
accidental catheter removal. Conclusions No significant differences in the
peripheral venous catheter sealing effects were observed between normal saline
and heparin saline usage in Chinese patients.
PMID- 28415938
TI - Indocyanine green detects sentinel lymph nodes in early breast cancer.
AB - Objective To explore the clinical value of indocyanine green (ICG) for the
fluorescence-guided detection of sentinel lymph nodes (SLNs) during sentinel
lymph node biopsy (SLNB) in patients with early breast cancer. Methods This
retrospective study included female patients with breast cancer. Patients were
administered methylene blue and ICG using standard techniques. All SLNs that were
collected during surgery were submitted for pathological examination. SLNs were
defined as those that were either fluorescent, blue, fluorescent and blue or
palpably suspicious. Surgical complications, axillary recurrence, distant
metastasis and overall survival rates were observed postoperatively. Results A
total of 60 patients were enrolled in the study. The fluorescence detection rate
of SLNs was 100% ( n = 177), with a mean of 2.95 SLNs per patient. The methylene
blue staining rate was 88.3% ( n = 106), with a mean of 1.77 SLNs per patient.
Pathological assessment of intraoperative frozen specimens revealed SLN
metastases in 10 patients, who immediately underwent axillary lymph node
dissection. No patient had axillary recurrence or distant metastases, with a
survival rate of 100%. Patients who underwent SLNB showed good appearance in the
axillary wound, with no limited shoulder joint abduction and upper limb oedema.
Conclusion Fluorescence-guided SLNB has several advantages and is suitable for
clinical application.
PMID- 28415939
TI - Molecular diagnosis of Chinese patients with 21-hydroxylase deficiency and
analysis of genotype-phenotype correlations.
AB - Objective The spectrum of molecular defects in Chinese patients with 21
hydroxylase deficiency (21-OHD), and genotype-phenotype relationships are
unknown. Methods We screened eight patients with non-classical (NC) 21-OHD and 35
with classical 21-OHD, and detected nine known mutations. Results The most
frequent mutation among the 43 21-OHD cases was p.Ile172Asn (allele frequency,
36.0%), followed by c.290-13A/C > G (20.9%), Del (8.6%), p.Pro30Leu (7.0%),
p.Gln318Ter (7.0%), p.Val281Leu (4.7%), p.Arg356Trp (2.3%), p.[Ile236Asn;
Val237Glu; Met239Lys] (2.3%), and E3Delta8 bp (1.2%). The frequency spectrum of
CYP21A2 mutations in the Chinese population was similar to that in the Japanese
population, except that p.Val281Leu was identified in Chinese NC21-OHD patients
at a frequency of 25.0%, whereas it was absent in Japanese patients. We found
that genotype could predict phenotype in 88.3% of patients. Conclusion Some
characteristics appear to be unique to the Chinese population, but genotype was
strongly predictive of phenotype.
PMID- 28415940
TI - Thymoma metastatic to liver and pancreas: case report and review of the
literature.
AB - A 71-year-old man presented with a thymic mass involving the superior vena cava.
A mediastinoscopical biopsy initially suggested a diagnosis of type A thymoma.
After neoadjuvant chemotherapy, the patient underwent en-bloc thymectomy and
vascular resection for a pathology-confirmed type B3 thymoma involving the
superior vena cava, the left brachiocephalic vein and the distal part of the
right brachiocephalic vein. Adjuvant radiotherapy was administered. Two years
after the primary surgery, abdominal computed tomography (CT) and whole body
fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans showed a
single hepatic lesion that was treated with wedge liver resection. Pathological
examination confirmed metastatic type B3 thymoma. Almost 4 years later, abdominal
CT and 18-FDG PET revealed a 2.9-cm solid mass involving the body of the
pancreas. Distal pancreatectomy with lymph node dissection was performed.
Pathological examination showed a pancreatic metastasis from a type B3 thymoma,
without lymph node involvement. The patient is alive and free of disease 6 months
after the pancreatectomy (68 months after the initial thymectomy surgery). Intra
abdominal recurrence and pancreatic metastases are very uncommon manifestations
of thymoma, but this event should be kept in mind when an abdominal mass is seen
during follow-up.
PMID- 28415942
TI - Evaluation of health-related quality of life in patients with tuberculosis who
completed treatment in Kiribati.
AB - Objective To examine the health-related quality of life (HRQoL) and related
factors among patients with smear-positive and smear-negative pulmonary
tuberculosis (TB) within 2 years after completion of directly observed treatment,
short course (DOTS), and to compare their HRQoL with a comparison group of
community-dwelling individuals without TB in South Tarawa, Kiribati. Methods A
cross-sectional questionnaire survey was conducted among 206 pulmonary TB
patients who had completed DOTS and 214 individuals without TB, from July to
September 2012. HRQoL was measured using the Short Form (36) Health Survey (SF
36). Results The patients with TB had a statistically significantly higher
physical component summary (PCS) score and mental component summary (MCS) score
on the SF-36 than the comparison group after adjustment for background
characteristics. However, the differences did not exceed the 3-point threshold
for clinically significant differences. Multiple liner regression showed that
older age and presence of persistent symptoms after completion of DOTS were
related to a lower PCS score in TB patients. Patients who were smear-positive
before DOTS treatment had higher MCS scores than those who were smear-negative.
Conclusions Our results suggest the effectiveness of DOTS treatment. Health
professionals can enhance HRQoL among posttreatment TB patients by managing their
symptoms.
PMID- 28415941
TI - Endothelial protein C receptor polymorphisms and risk of sepsis in a Chinese
population.
AB - Objective To examine the potential relationship of EPCR polymorphisms and the
risk of sepsis in a Chinese population. Methods Snapshot SNP genotyping assays
and DNA sequencing methods were used to detect polymorphisms of the EPCR gene,
rs2069948C/T (2532C/T) and rs867186A/G (6936A/G), in 64 patients with sepsis and
in 113 controls. Soluble EPCR (sEPCR) was measured by ELISA. Results There were
significant differences in the allele and genotype frequencies of EPCR gene
rs2069948C/T and allele frequencies of rs867186A/G between male and female
patients and controls. Females carrying rs2069948 C/T genotype or T allele and
males carrying rs867186 A allele were associated with a significantly increased
risk of sepsis. Plasma sEPCR levels of sepsis patients were higher than controls
and showed no correlation with EPCR gene polymorphisms. Conclusions EPCR
polymorphisms may be associated with increased risk of sepsis, but this has no
effect on the release of sEPCR in patients with sepsis.
PMID- 28415943
TI - Effects of scalp block with bupivacaine versus levobupivacaine on haemodynamic
response to head pinning and comparative efficacies in postoperative analgesia: A
randomized controlled trial.
AB - Objective This study was performed to determine the effects of scalp blocks with
bupivacaine versus levobupivacaine on the haemodynamic response during craniotomy
and the efficacies and analgesic requirements of these drugs postoperatively.
Methods This randomized, prospective, placebo-controlled, double-blind study
included 90 patients (age, 18-85 years; American Society of Anesthesiologists
physical status, I or II). The patients were randomly divided into three groups:
those who received 20 mL of 0.5% bupivacaine (Group B, n = 30), 20 mL of 0.5%
levobupivacaine (Group L, n = 30), or saline as a placebo (Group C, n = 30).
Scalp blocks were performed 5 min before head pinning. The primary outcome was
the mean arterial pressure (MAP), and the secondary outcomes were the heart rate
(HR), visual analogue scale (VAS) scores, and additional intraoperative and
postoperative drug use. Postoperative pain was evaluated using a 10-cm VAS.
Results During head pinning and incision, the MAP and HR were significantly
higher in Group C. The additional drug requirement for intraoperative
hypertension and tachycardia was significantly higher in Group C. There were no
significant differences in MAP, HR, or VAS scores between Groups B and L.
Conclusion Both bupivacaine and levobupivacaine can be effectively and safely
used for scalp blocks to control haemodynamic responses and postoperative pain.
PMID- 28415945
TI - Pseudomonas aeruginosa endophthalmitis caused by accidental iatrogenic ocular
injury with a hypodermic needle.
AB - Iatrogenic traumatic endophthalmitis is a rare but serious ocular infection that
can lead to severe vision loss. A 44-year-old man presented with pain and
decreased vision in the right eye 4 hours after injury with a hypodermic needle
during irrigation of his eye. Slit-lamp examination revealed a penetrating
corneal puncture and iris hole in the right eye. Twenty hours later, his visual
acuity had decreased to hand motion, and severe fibrinoid uveitis was noted. He
immediately underwent irrigation of the anterior chamber and intravitreal
antibiotic injection. The right eye became painful again, and emergent vitrectomy
combined with lensectomy was performed along with intravitreal antibiotic
administration. The patient remained stable during the 2-month follow-up.
Standard practice should be adopted when irrigating the eye to prevent this type
of injury, and emergent surgical intervention is very important to preserve
visual function.
PMID- 28415944
TI - Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic
kidney disease: a meta-analysis.
AB - Objective This meta-analysis aimed to investigate the efficacy and safety of
pentoxifylline (PTF) plus angiotensin-converting enzyme inhibitors
(ACEIs)/angiotensin receptor blockers (ARBs) for proteinuria and kidney function
in chronic kidney disease (CKD). Methods CENTRAL, EMBASE, Ovid-MEDLINE, PubMed,
and CNKI were searched for relevant, randomized, controlled trials (RCTs). A meta
analysis was performed to review the effect of PTF plus ACEIs/ARBs vs. ACEIs/ARBs
alone on proteinuria and kidney function in CKD. Results Eleven RCTs including
705 patients were retrieved. PTF plus ACEI/ARB treatment significantly decreased
proteinuria in patients with CKD within 6 months (standard mean difference [SMD]
0.52; 95% CI -0.90 to 0.15; I2 = 68%) and significantly attenuated a decrease in
estimated glomerular filtration rate (eGFR) in patients with stages 3-5 CKD after
6 months of treatment (standard mean difference [SMD] 0.30; confidence limit [Cl]
95% CI 0.06 to 0.54; I2 = 0%). PTF plus ACEIs/ARBs for 9 to 12 months
significantly reduced albuminuria in patients with CKD (SMD-0.30, 95% CI -0.57 to
0.03; I2 = 0%) and alleviated the decline in eGFR in patients with stages 3-5 CKD
(SMD 0.51; 95% CI 0.06 to 0.96; I2 = 61%). Conclusion The combination of an ACEI
or ARB and PTF has a protective effect in reducing proteinuria by ameliorating
the decline in eGFR in patients with stages 3-5 CKD.
PMID- 28415946
TI - Azacitidine-induced acute lung injury in a patient with therapy-related
myelodysplastic syndrome.
AB - Azacitidine is a first-in-class demethylating agent, and it is widely used
globally as a first-line treatment for higher-risk myelodysplastic syndrome
(MDS). Here, we report the case of a patient with MDS who suffered from a rare
adverse event, an acute lung injury (ALI), which was suspected to have been
caused by azacitidine and was successfully treated with corticosteroids. As it is
a rare, but critical, adverse event, clinicians should consider ALI as one of the
differential diagnoses in cases where 1) pneumonia and fever of unknown etiology
arise in MDS patients treated with azacitidine, 2) antimicrobial agents are not
effective, and 3) microbiological tests produce negative results.
PMID- 28415947
TI - Effect of pretreatment with midazolam on etomidate-induced myoclonus: A meta
analysis.
AB - Objective To investigate the effect of pretreatment with midazolam on myoclonus
induced by etomidate injection. Methods A meta-analysis was performed using
Review Manager software, version 5.2. Two researchers independently searched
PubMed, Cochrane Library, and Embase(r) databases for randomized controlled
trials involving patients who underwent etomidate induced general anaesthesia
with or without midazolam pretreatment, published between 1990 and 2016. Outcome
measures comprised overall myoclonus incidence rate and incidence rate classified
by degree of myoclonus following etomidate injection. Data were assessed using a
fixed effects model. Results Five studies, comprising 302 patients, were included
for analysis. Overall incidence rate of etomidate injection-induced myoclonus was
significantly lower in the pooled midazolam group versus controls (relative risk
[RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree
of myoclonus showed significantly lower incidence in midazolam groups versus
control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate
myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI
0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced
myoclonus, and alleviate the degree of etomidate-induced myoclonus.
PMID- 28415948
TI - Use of platelet-rich plasma for regeneration in non-vital immature permanent
teeth: Clinical and cone-beam computed tomography evaluation.
AB - Objective This study was performed to assess the clinical and radiological
outcomes of a revascularization procedure in immature teeth with apical
periodontitis using platelet-rich plasma (PRP). The PRP protocol and conventional
revascularization protocol, which used a blood clot as the scaffold, were
compared. Methods Thirty non-vital immature permanent teeth were randomly
categorized into two groups. After disinfecting the root canal space with triple
antibiotic paste (1:1:1 ciprofloxacin, metronidazole, and cefaclor), a tissue
scaffold was created using either PRP or a blood clot (control) and covered with
white mineral trioxide aggregate. All cases were followed up clinically and
radiographically for 12 months. Differences in bone density, root length, and
lesion size were calculated using preoperative and postoperative computed
tomography images. The means of the differences in individual parameters in the
blood clot and PRP groups were compared using the Mann-Whitney U test. Results
After 5 months, sensitivity tests (cold and electric pulp tests) elicited a
delayed positive response in 23 sites. At 12 months, cone-beam computed
tomography revealed resolution or a decrease in lesion size and an increase in
bone density in all 30 (100%) teeth. Additionally, continued root development was
observed in 22 (73%) teeth and early root growth was observed in the test group
(mineral trioxide aggregate with PRP). Conclusions The results of this study
suggest that PRP can serve as a successful scaffold for regenerative endodontic
treatment. With the exception of a significant increase in root length, the
results of treatment with PRP were not significantly different from those of the
conventional protocol using a blood clot as the scaffold.
PMID- 28415949
TI - beta-catenin promotes intracellular bacterial killing via suppression of
Pseudomonas aeruginosa-triggered macrophage autophagy.
AB - Objective To investigate beta-catenin-mediated bacterial elimination during
Pseudomonas aeruginosa infection of macrophage-like RAW264.7 cells. Methods Cell
viability and catenin beta 1 ( CTNNB1) expression in RAW264.7 cells following P.
aeruginosa infection versus uninfected cells, were detected by cell counting kit
8 assay and beta-catenin Western blots. RAW264.7 cells with CTNNB1 overexpression
were established with beta-catenin lentivirus using flow cytometry and clonogenic
limiting dilution assays. Bacterial killing was measured by plate counts;
phagocytosis and nitric oxide (NO) were measured by flow cytometry; and reactive
oxygen species (ROS) were measured using Griess reaction. Autophagy was
determined by microtubule-associated protein 1 light chain 3 alpha
phosphatidylethanolamine conjugate (LC3-II) protein levels and formation of LC3
puncta, using Western blot and immunofluorescence staining. Results Following P.
aeruginosa infection, RAW264.7 cell beta-catenin levels were reduced in a time-
and multiplicity of infection-dependent manner. CTNNB1 overexpression was
associated with increased P. aeruginosa elimination, but had no effect on
RAW264.7 cell phagocytosis, ROS and NO. CTNNB1 overexpression reduced LC3-II
levels and formation of LC3 puncta, suggesting autophagy inhibition.
Rapamycin/starvation-induced autophagy resulted in reduced bacterial killing
following P. aeruginosa infection. Conclusion beta-catenin may promote bacterial
killing via suppression of P. aeruginosa-induced macrophage autophagy.
PMID- 28415950
TI - Ovarian cystectomy in the treatment of apparent early-stage immature teratoma.
AB - Objective To investigate the role of ovarian cystectomy in patients with early
stage immature teratoma. Methods A retrospective review was undertaken on
patients diagnosed pathologically with immature teratoma and with malignant
lesions confined to the ovary. Patients were included if they had been treated
between January 1997 and December 2015 at the Obstetrics and Gynaecology Hospital
of Fudan University, Shanghai, China. Relevant demographic and clinical data were
retrieved from the medical records. Results Forty-three patients were included in
the study; 14 underwent ovarian cystectomy (group 1) and 29 underwent unilateral
salpingo-oophorectomy (USO; group 2). Three of the patients who underwent USO
relapsed and required a second surgical intervention. The 5-year disease-free
survival rates were 100% and 88%for groups 1 and 2, respectively. There were no
significant differences between the two groups in terms of survival or
postoperative fertility outcomes. Univariate and multivariate analysis further
revealed that ovarian cystectomy was not a poor prognostic indicator for disease
free survival. Conclusion These current data suggest that ovarian cystectomy can
be considered for patients with apparent early-stage immature teratoma as it
preserves fertility as much as possible without adversely impacting upon
survival.
PMID- 28415951
TI - Superior versus anteroinferior plating of displaced midshaft clavicular fracture
in patients older than 60 years.
AB - Objective To compare superior versus anteroinferior plating for displaced
midshaft clavicular fracture in elderly patients. Methods We retrospectively
compared the functional result, parameters, and perioperative course of displaced
midshaft clavicular fracture in 42 patients >60 years treated with a 3.5-mm
reconstruction plate placed superiorly versus anteroinferiorly. Results Groups
were similar with regard to age, sex, bone mineral density, cause of injury, and
fracture pattern. The superiorly-plated group had a significantly longer
operation time and greater blood loss, complications and implant prominence.
Constant scores were significantly higher for the anteroinferiorly-plated group
than the superiorly-plated group at 3 months postoperatively; however, there was
no difference between groups at final follow-up. Conclusion While both
anteroinferior and superior plate placement are safe and effective for displaced
midclavicular fractures in patients >60 years, the anteroinferior approach
involves less operation time, blood loss, complications and implant prominence,
and enables faster return to normal activities.
PMID- 28415952
TI - Effective treatment of ketamine-associated cystitis with botulinum toxin type a
injection combined with bladder hydrodistention.
AB - Objective Ketamine-associated cystitis (KAC) has been described in a few case
reports, but its treatment in a relatively large number of patients has not been
documented. This study aimed to describe our experience of treatment of 36
patients with KAC. Methods Thirty-six patients (30 males and 6 females, aged 19
38 years) with KAC, who had previously taken a muscarinic receptor blocker and/or
antibiotics, but without symptomatic relief, were treated with botulinum toxin A
injection combined with bladder hydrodistention. Urodynamic testing, and the
O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI)
were used to evaluate baseline values and improvement before and after the
treatment. Results One month post-treatment, all patients achieved marked relief
of symptoms. The nocturia time was markedly reduced, while bladder capacity, the
interval between micturition, the void volume, and the maximum flow rate were
remarkably increased at 1 month. Additionally, the ICSI and ICPI were
significantly improved. Conclusion Botulinum toxin A injection along with bladder
hydrodistention is effective for managing KAC.
PMID- 28415953
TI - Influence of etanercept on leptin and ghrelin secretion in children with juvenile
idiopathic arthritis.
AB - Objective To assess possible changes in leptin and ghrelin secretion due to
etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA
and 16 age-matched controls were enrolled into this prospective, cross-sectional
study. Serum leptin, total and acyl ghrelin were measured in addition to white
blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept
and 25 conventional therapies (including methotrexate) for JIA. There was no
difference between treatment and control groups in leptin or ghrelin levels and
no evidence of a relationship between leptin and ghrelin in patients with JIA. In
all children with JIA there was a correlation between leptin and body mass index
(BMI). However, compared with children in the conventional treatment group,
children in the etanercept group showed a positive correlation between total
ghrelin and BMI and those with a low BMI showed a negative correlation between
acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin
concentrations were found when patients with JIA and controls were compared or
when patients who received etanercept were compared with those who received
conventional treatment for JIA.
PMID- 28415954
TI - Healthcare budgets across continents: at crossroads - publish or perish.
PMID- 28415956
TI - The relationship between neutrophil-lymphocyte ratio and acute aortic dissection.
PMID- 28415957
TI - "So Happy I Could Shout!" and "So Happy I Could Cry!" Dimorphous expressions
represent and communicate motivational aspects of positive emotions.
AB - Happiness can be expressed through smiles. Happiness can also be expressed
through physical displays that without context, would appear to be sadness
(tears, downward turned mouths, and crumpled body postures) and anger (clenched
jaws, snarled lips, furrowed brows, and pumped fists). These seemingly
incongruent displays of happiness, termed dimorphous expressions, we propose,
represent and communicate expressers' motivational orientations. When
participants reported their own aggressive expressions in positive or negative
contexts, their expressions represented positive or negative emotional
experiences respectively, imbued with appetitive orientations (feelings of
wanting to go). In contrast, reported sad expressions, in positive or negative
contexts, represented positive and negative emotional experiences respectively,
imbued with consummatory orientations (feelings of wanting to pause). In six
additional experiments, participant observers interpreted that aggression
displayed in positive contexts signalled happy-appetitive states, and sadness
displayed in positive contexts signalled happy-consummatory states. Implications
for the production and interpretation of emotion expressions are discussed.
PMID- 28415958
TI - Glycyrrhizic acid exerts anti-inflammatory effect to improve cerebral vasospasm
secondary to subarachnoid hemorrhage in a rat model.
AB - This study aimed to investigate the therapeutic effect of glycyrrhizic acid (GA)
on the cerebral vasospasm (CVS) in a rat subarachnoid hemorrhage (SAH) model and
to explore the potential mechanism. A total of 44 healthy male rats were randomly
assigned into 3 groups: control group (n = 12), SAH group (n = 16) and GA group
(n = 16). No treatment was conducted in control group; in SAH group and GA group,
experimental CVS was induced using a double-hemorrhage model and then rats were
intraperitoneally injected with normal saline and GA at 10 mg/kg, respectively,
once daily. Three days later, neurological function was evaluated. Then, animals
were sacrificed, and the basilar artery was collected. The inner diameter and
vascular wall thickness were determined. Western blotting was employed to detect
high mobility group protein B1 (HMGB1) protein expression and RT-PCR to detect
the mRNA expression of IL-1beta, IL-6, TNF-alpha, and IL-10 in the basilar
artery. GA treatment significantly improved the neurological function following
SAH. In GA group, the basilar artery diameter increased markedly and vascular
wall thickness reduced significantly when compared with SAH group (p < 0.05).
HMGB1 protein expression and mRNA expression of IL-1beta, IL-6, TNF-alpha, and IL
10 in SAH group were significantly higher than in control group (p < 0.05).
However, GA dramatically reduced IL-1beta, IL-6, and TNF-alpha, and further
elevated IL-10 expression as compared to SAH group (p < 0.05). GA may inhibit
HMGB1 expression and subsequent production of inflammatory cytokines to prevent
CVS following SAH.
PMID- 28415959
TI - The Practices and Meanings of Care for Nurses Working on a Pediatric Bone Marrow
Transplant Unit.
AB - Bone marrow transplant (BMT) units are stressful work environments with high
staff burnout, anxiety, and turnover. A qualitative study was undertaken to
better understand care for nurses within the context of their clinical practice
on a pediatric BMT unit. Understanding care practices for BMT nurses will allow
us to design interventions and provide appropriate support for this subspecialty
of nurses. Focus groups were held with 24 nurses as key participants, and 2 focus
groups with general participants: unit management (N = 2) and caregivers of
inpatients (N = 7). Data were analyzed using a thematic analysis. Data were
transcribed verbatim and coded to consensus by members of the research team. Five
themes emerged from the data: ( a) experiencing stressful situations that impede
care, ( b) growing and developing personally and professionally, ( c) providing
trustworthy and respectful care, ( d) acquiring meaningful coping skills, and (
e) sharing with others versus isolation. Stress management, professional
development, and interdisciplinary communication were areas that emerged for
potential intervention.
PMID- 28415960
TI - Chemotherapy Safety Standards: A Pediatric Perspective.
PMID- 28415961
TI - Changing practices and shifting meanings of female genital cutting among the
Maasai of Arusha and Manyara regions of Tanzania.
AB - Using mixed methods that combined participant observation and semi-structured in
depth interviews, this study looked at changing practices and shifting meanings
of female genital cutting among the Maasai people in Tanzania. The findings
suggest that an increasing social pressure to abandon female genital cutting has
inspired the hiding of the practice, causing the actual cutting to become
detached from its traditional ceremonial connotations. This detaching of cutting
from ceremony has created a shift in meanings: the ceremony still carries the
meaning of passage into adulthood, while the cutting seems to function as a way
of inscribing Maasai identity into the body. The detaching of genital cutting
from ceremony offers those willing to continue the practice the opportunity to do
so without being prosecuted, and those unwilling to undergo or perform the
practice the opportunity to evade it by faking the cutting without being socially
sanctioned for it. Findings also suggest changing attitudes towards the practice
among the younger generation as the result of education. Maasai culture and the
practice of female genital cutting are not static but actively challenged and
reinterpreted from within the community, with formally schooled and women taking
up leading roles in reshaping gender norms.
PMID- 28415962
TI - Guest Editorial: Introducing a new section.
PMID- 28415963
TI - Impact of the MDM2 splice-variants MDM2-A, MDM2-B and MDM2-C on cytotoxic stress
response in breast cancer cells.
AB - BACKGROUND: The murine double minute 2 (MDM2) is an oncogene and a negative
regulator of the tumor suppressor protein p53. MDM2 is known to be amplified in
numerous human cancers, and upregulation of MDM2 is considered to be an
alternative mechanism of p53 inactivation. The presence of many splice variants
of MDM2 has been observed in both normal tissues and malignant cells; however
their impact and functional properties in response to chemotherapy treatment are
not fully understood. Here, we investigate the biological effects of three widely
expressed alternatively spliced variants of MDM2; MDM2-A, MDM2-B and MDM2-C, both
in unstressed MCF-7 breast cancer cells and in cells subjected to chemotherapy.
We assessed protein stability, subcellular localization and induction of
downstream genes known to be regulated by the MDM2-network, as well as impact on
cellular endpoints, such as apoptosis, cell cycle arrest and senescence. RESULTS:
We found both the splice variants MDM2-B and -C, to have a much longer half-life
than MDM2 full-length (FL) protein after chemotherapy treatment indicating that,
under stressed conditions, the regulation of degradation of these two variants
differs from that of MDM2-FL. Interestingly, we observed all three splice
variants to deviate from MDM2-FL protein with respect to subcellular
distribution. Furthermore, while MDM2-A and -B induced the expression of the pro
apoptotic gene PUMA, this effect did not manifest in an increased level of
apoptosis. CONCLUSION: Although MDM2-B induced slight changes in the cell cycle
profile, overall, we found the impact of the three MDM2 splice variants on
potential cellular endpoints upon doxorubicin treatment to be limited.
PMID- 28415964
TI - Quantitative trait locus analysis of heterosis for plant height and ear height in
an elite maize hybrid zhengdan 958 by design III.
AB - BACKGROUND: Plant height (PH) and ear height (EH) are two important agronomic
traits in maize selection breeding. F1 hybrid exhibit significant heterosis for
PH and EH as compared to their parental inbred lines. To understand the genetic
basis of heterosis controlling PH and EH, we conducted quantitative trait locus
(QTL) analysis using a recombinant inbreed line (RIL) based design III population
derived from the elite maize hybrid Zhengdan 958 in five environments. RESULTS: A
total of 14 environmentally stable QTLs were identified, and the number of QTLs
for Z1 and Z2 populations was six and eight, respectively. Notably, all the eight
environmentally stable QTLs for Z2 were characterized by overdominance effect
(OD), suggesting that overdominant QTLs were the most important contributors to
heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were
anchored on six genomic regions, among which four are trait-specific QTLs,
suggesting that the genetic basis for PH and EH is partially different.
Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further
validated in backcross populations. CONCLUSIONS: The genetic basis for PH and EH
is partially different, and overdominant QTLs are important factors for heterosis
of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic
improvement of maize plant height.
PMID- 28415965
TI - The Pregnancy Environment and Lifestyle Study (PETALS): a population-based
longitudinal multi-racial birth cohort.
AB - BACKGROUND: Increasing recognition has been received regarding the proven and
suggested links between multi-level environmental exposures on a broad scale
(e.g., chemical, clinical, behavioral, physical and social) and health deficits
originated from the critical window of development. However, such prospective
human data are limited. In 2016, the National Institutes of Health funded 35
centers comprising 84 extant cohorts for the Environmental Influences on Child
Health Outcomes (ECHO) pediatric cohorts program. The Pregnancy Environment and
Lifestyle Study (PETALS) is one of the cohorts at the participating centers of
Kaiser Permanente Northern California (KPNC). METHODS: PETALS was originally
funded by the National Institute of Environmental Health Sciences to establish a
longitudinal birth cohort of 3,350 mother-infant pairs and conduct a nested case
control study of 300 women with gestational diabetes (GDM) and 600 matched
controls to investigate the associations between phenol exposures in first and
second trimesters and GDM risk and the related outcome of infant macrosomia. This
paper describes the prospective cohort design of PETALS, current research
activities, and cohort profile of enrolled women who delivered as of February
2016. Women are enrolled from the KPNC membership. Fasting blood draw, urine
collection, anthropometric measurements, and questionnaires on health history and
lifestyle are completed at baseline and follow-up clinic visits with targeted
windows of 10-13 and 16-19 weeks of gestation, respectively. Further, women's
clinical and health assessments before and after the index pregnancy in addition
to their children's birth outcomes and health information can be abstracted from
electronic health records, allowing future follow-up. Study data could also be
linked and extended to a myriad of additional observational data including
environmental and area-level databases and census data. DISCUSSION: In this
racially- and ethnically-diverse pregnancy cohort, the generated biospecimen and
data repository will establish a comprehensive framework which may provide unique
opportunities to address a multitude of research questions on the intrauterine
environment and adverse pregnancy and birth outcomes in a representative multi
racial/ethnic population with generalizable findings.
PMID- 28415966
TI - Birth by caesarean section and school performance in Swedish adolescents- a
population-based study.
AB - BACKGROUND: Our objective was to assess the impact of obstetric mode of delivery,
and in particular birth by Caesarean section (CS), on school performance in
adolescents using a large, population-based cohort. METHODS: We extracted data
from the Swedish Medical Birth Register and National School Register. We included
all live singleton births in Sweden from 1982-1995 (n = 1,489,925). School grades
were reported on a scale from 0 to 320, scores less than 160 (i.e. "pass") were
considered to be "poor school performance." Mode of delivery was categorised as:
unassisted vaginal delivery (VD), assisted VD, elective CS and emergency CS. We
measured the association between mode of delivery and "poor school performance"
using logistic regression. We then used quantile regression to assess the
association between mode of delivery and school performance across the
distribution of scores. We adjusted for maternal age, parity, small and large for
gestational age, gestational age, maternal country of birth, maternal depression,
non-affective disorder or bipolar disorder, parental income at time of birth, and
parental social welfare at time of birth. We also conducted sensitivity analyses
to investigate the association further. RESULTS: With logistic regression
analysis, the adjusted odds ratio (aOR) of assisted VD and poor school
performance, compared to unassisted VD, was 1.06 (95% CI: 1.03-1.08). For
elective CS it was 1.06 (95% CI:1.03-1.09) and for emergency CS it was 1.12 (95%
CI: 1.09-1.15). With quantile regression, assisted VD showed little difference in
scores, when compared to unassisted VD, at any point across the distribution.
Elective CS was associated with a 1-3 point decrease in scores, and emergency CS
was associated with a 2-5 point decrease in scores. CONCLUSION: A slight
association was found between birth by CS and school performance. However, the
effect was quite small and given the complex nature of the relationship, should
be interpreted with caution.
PMID- 28415967
TI - Chewing gum for intestinal function recovery after caesarean section: a
systematic review and meta-analysis.
AB - BACKGROUND: Gum chewing has been reported to enhance the intestinal function
recovery after caesarean section, current perspectives and practice guidelines
vary widely on the use of gum chewing, more studies on the role of gum chewing
after caesarean section are needed. METHODS: We performed a comprehensive,
systematic meta-analysis of randomized controlled trials (RCTs) on the efficacy
of gum chewing after caesarean section. Studies were identified by searching
EMBASE et al database (until June 30, 2016). Summary odd ratios or weighted mean
differences with 95% confidence intervals were calculated for each outcome with
fixed- or random-effects model. RESULTS: Ten RCTs with a total of 1659 women were
included in our meta-analysis. Gum chewing provided significant benefits in
reducing the time to first passage of flatus, first defecation, first bowel
sound, first bowel movement and the length of hospital stay, but not in the time
to first feeling of hunger. CONCLUSIONS: Gun chewing hastens the intestinal
function recovery after caesarean section and offers a safe and inexpensive
option. High-quality and larger-scale RCTs are still warranted to clarify the
role of gum chewing in intestinal function recovery after caesarean section.
PMID- 28415968
TI - How to explore the needs of informal caregivers of individuals with cognitive
impairment in Alzheimer's disease or related diseases? A systematic review of
quantitative and qualitative studies.
AB - BACKGROUND: This study aims to review the methodologies used to identify the
needs, the existing needs assessment instruments and the main topics of needs
explored among caregivers of patients with mild cognitive impairment to dementia.
METHODS: MEDLINE, PsycINFO, The Cochrane Library and Web of science were searched
from January 1980 to January 2017. Research studies in English or French were
eligible for inclusion if they fulfilled the following criteria: quantitative,
qualitative and mixed method studies that used instrument, focus group or semi
structured interviews to assess the informal caregiver's needs in terms of
information, coping skills, support and service. RESULTS: Seventy studies (n = 39
quantitative studies, n = 25 qualitative studies and n = 6 mixed method studies)
met the inclusion criteria and were included. Thirty-six quantitative instruments
were identified but only one has been validated for the needs assessment of
dementia caregivers: the Carer's Needs Assessment for Dementia (CNA-D). The main
areas of needs explored in these instruments were: information, psychosocial,
social, psychoeducational and other needs. CONCLUSIONS: No instrument has been
developed and validated to assess the needs of informal caregivers of patients
with cognitive impairment, whatever the stage and the etiology of the disease. As
the perceived needs of caregivers may evolve with the progression of the disease
and the dementia transition, their needs should be regularly assessed.
PMID- 28415969
TI - Carbapenem resistance, inappropriate empiric treatment and outcomes among
patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia
and sepsis.
AB - BACKGROUND: Drug resistance among gram-negative pathogens is a risk factor for
inappropriate empiric treatment (IET), which in turn increases the risk for
mortality. We explored the impact of carbapenem-resistant Enterobacteriaceae
(CRE) on the risk of IET and of IET on outcomes in patients with
Enterobacteriaceae infections. METHODS: We conducted a retrospective cohort study
in Premier Perspective database (2009-2013) of 175 US hospitals. We included all
adult patients with community-onset culture-positive urinary tract infection
(UTI), pneumonia, or sepsis as a principal diagnosis, or as a secondary diagnosis
in the setting of respiratory failure, treated with antibiotics within 2 days of
admission. We employed regression modeling to compute adjusted association of
presence of CRE with risk of receiving IET, and of IET on hospital mortality,
length of stay (LOS) and costs. RESULTS: Among 40,137 patients presenting to the
hospital with an Enterobacteriaceae UTI, pneumonia or sepsis, 1227 (3.1%) were
CRE. In both groups, the majority of the cases were UTI (51.4% CRE and 54.3% non
CRE). Those with CRE were younger (66.6+/-15.3 vs. 69.1+/-15.9 years, p < 0.001),
and more likely to be African-American (19.7% vs. 14.0%, p < 0.001) than those
with non-CRE. Both chronic (Charlson score 2.0+/-2.0 vs. 1.9+/-2.1, p = 0.009)
and acute (by day 2: ICU 56.3% vs. 30.4%, p < 0.001, and mechanical ventilation
35.8% vs. 11.7%, p < 0.001) illness burdens were higher among CRE than non-CRE
subjects, respectively. CRE patients were 3* more likely to receive IET than non
CRE (46.5% vs. 11.8%, p < 0.001). In a regression model CRE was a strong
predictor of receiving IET (adjusted relative risk ratio 3.95, 95% confidence
interval 3.5 to 4.5, p < 0.001). In turn, IET was associated with an adjusted
rise in mortality of 12% (95% confidence interval 3% to 23%), and an excess of
5.2 days (95% confidence interval 4.8, 5.6, p < 0.001) LOS and $10,312 (95%
confidence interval $9497, $11,126, p < 0.001) in costs. CONCLUSIONS: In this
large US database, the prevalence of CRE among patients with Enterobacteriaceae
UTI, pneumonia or sepsis was comparable to other national estimates. Infection
with CRE was associated with a four-fold increased risk of receiving IET, which
in turn increased mortality, LOS and costs.
PMID- 28415970
TI - Drosophila melanogaster retrotransposon and inverted repeat-derived endogenous
siRNAs are differentially processed in distinct cellular locations.
AB - BACKGROUND: Endogenous small interfering (esi)RNAs repress mRNA levels and
retrotransposon mobility in Drosophila somatic cells by poorly understood
mechanisms. 21 nucleotide esiRNAs are primarily generated from retrotransposons
and two inverted repeat (hairpin) loci in Drosophila culture cells in a Dicer2
dependent manner. Additionally, proteins involved in 3' end processing, such as
Symplekin, CPSF73 and CPSR100, have been recently implicated in the esiRNA
pathway. RESULTS: Here we present evidence of overlap between two essential RNA
metabolic pathways: esiRNA biogenesis and mRNA 3' end processing. We have
identified a nucleus-specific interaction between the essential esiRNA cleavage
enzyme Dicer2 (Dcr2) and Symplekin, a component of the core cleavage complex
(CCC) required for 3' end processing of all eukaryotic mRNAs. This interaction is
mediated by the N-terminal 271 amino acids of Symplekin; CCC factors CPSF73 and
CPSF100 do not contact Dcr2. While Dcr2 binds the CCC, Dcr2 knockdown does not
affect mRNA 3' end formation. RNAi-depletion of CCC components Symplekin and
CPSF73 causes perturbations in esiRNA abundance that correlate with fluctuations
in retrotransposon and hairpin esiRNA precursor levels. We also discovered that
esiRNAs generated from retrotransposons and hairpins have distinct physical
characteristics including a higher predominance of 22 nucleotide hairpin-derived
esiRNAs and differences in 3' and 5' base preference. Additionally,
retrotransposon precursors and derived esiRNAs are highly enriched in the nucleus
while hairpins and hairpin derived esiRNAs are predominantly cytoplasmic similar
to canonical mRNAs. RNAi-depletion of either CPSF73 or Symplekin results in
nuclear retention of both hairpin and retrotransposon precursors suggesting that
polyadenylation indirectly affects cellular localization of Dcr2 substrates.
CONCLUSIONS: Together, these observations support a novel mechanism in which
differences in localization of esiRNA precursors impacts esiRNA biogenesis.
Hairpin-derived esiRNAs are generated in the cytoplasm independent of Dcr2
Symplekin interactions, while retrotransposons are processed in the nucleus.
PMID- 28415971
TI - An evolutionarily conserved transcriptional response to viral infection in
Caenorhabditis nematodes.
AB - BACKGROUND: Caenorhabditis elegans is a powerful model organism for probing many
biological processes including host-pathogen interactions with bacteria and
fungi. The recent identification of nematode viruses that naturally infect C.
elegans and Caenorhabditis briggsae provides a unique opportunity to define host
virus interactions in these model hosts. RESULTS: We analyzed the transcriptional
response of pathogen infected C. elegans and C. briggsae by RNA-seq. We
identified a total of 320 differentially expressed genes (DEGs) in C. elegans
following Orsay virus infection. The DEGs of known function were enriched for
ubiquitin ligase related genes; however, the majority of the genes were of
unknown function. Interestingly, many DEGs that responded to Orsay virus
infection were similar to those induced by Nematocida parisii infection, which is
a natural microsporidia pathogen of C. elegans that like Orsay virus infects
intestinal cells. Furthermore, comparison of the Orsay virus DEGs in C. elegans
to Santeuil virus DEGs in C. briggsae identified 58 C. elegans genes whose
orthologs were likewise differentially expressed in C. briggsae, thereby defining
an evolutionarily conserved response to viral infection. CONCLUSIONS: The two
different species C. elegans and C. briggsae, which diverged ~18 million years
ago, share a common set of transcriptionally responsive genes to viral infection.
Furthermore, a subset of these genes were also differentially expressed following
infection by a eukaryotic pathogen, N. parisii, suggesting that these genes may
constitute a broader pan-microbial response to infection.
PMID- 28415972
TI - Community-based survey during rabies outbreaks in Rangjung town, Trashigang,
eastern Bhutan, 2016.
AB - BACKGROUND: Rabies is a highly fatal disease transmitted through the bite of a
rabid animal. Human deaths can be prevented by prompt administering of rabies
vaccine and rabies immunoglobulin following the exposure. An assessment of
community knowledge, awareness and practices on rabies is important during
outbreak to understand their preparedness and target educational messages and
response activities by the rapid response team. METHODS: A rabies outbreak has
occurred in Rangjung town, eastern Bhutan on 4 October 2016. A rapid response
team was activated to investigate outbreak and to establish a control program. A
community-based questionnaire survey was conducted from 20 to 21 October 2016 to
assess the community knowledge of rabies to guide outbreak preparedness and also
target educational messages and response activities by the RRT. RESULTS: A total
of 67 respondents were interviewed, of which 61% were female and 39% male. All
the respondents have heard of rabies (100%), have knowledge on source of rabies
(dog) and its mode of transmission in animals and humans. Most (61%) respondents
were aware and also indicated that they would wash the animal bite wound with
soap and water and seek medical care on the same day of exposure (100%). Majority
(94%) of the respondents have indicated that they would report to the government
agencies if they see any suspected rabid dogs in the community and suggested
various control measures for dog population management and rabies in Rangjung
including neutering procedure and mass dog vaccination. Although only few (10%)
of the respondents households owned dogs and cats, but 50% of them have indicated
that their dogs were allowed to roam outside the home premises posing risk of
contracting rabies through rabid dog bites. CONCLUSIONS: Although this study
indicates a high level of knowledge and awareness on rabies among the community,
there exists some knowledge gaps about rabies and therefore, an awareness
education should be focused on the source of rabies and rabies virus transmission
route to reduce public concern on nonexposure events thereby reducing the cost on
unnecessary postexposure treatment.
PMID- 28415973
TI - Effect of the PREPARE intervention on sexual initiation and condom use among
adolescents aged 12-14: a cluster randomised controlled trial in Dar es Salaam,
Tanzania.
AB - BACKGROUND: Unsafe sexual practices continue to put adolescents at risk for a
number of negative health outcomes in Tanzania. While there are some effective
theory-based intervention packages with positive impact on important mediators of
sexual behaviours, a context specific and tested intervention is urgently needed
in Tanzania. PURPOSE: To develop and evaluate an intervention that will have a
significant effect in reducing sexual initiation and promoting condom use among
adolescents aged 12-14 in Dar es Salaam, Tanzania. DESIGN: A school-based Cluster
Randomised Controlled Trial was conducted during 2011-2014 in Kinondoni
Municipality. METHODS: A total of 38 public primary schools were randomly
selected, of which half were assigned to the intervention and half to the control
group based on their size and geographic location. Participants were interviewed
using a self-administered questionnaire at baseline before the PREPARE
intervention and then, 6 and 12 months following intervention. The primary
outcomes were self-reported sex initiation and condom use during the past 6
months. Data analysis was done using Generalized Estimating Equation (GEE)
modelling controlling for repeated measures and clustering of students within
schools. RESULTS: A total of 5091 students were recruited at baseline, and
interviewed again at 6 (n = 4783) and 12 months (n = 4370). Mean age of
participants at baseline was 12.4 years. Baseline sociodemographic, psychometric
and behavioural characteristics did not significantly differ between the two
study arms. The GEE analysis indicated that the intervention had a significant
effect on sexual initiation in both sexes after controlling for clustering and
correlated repeated measures. A significantly higher level of action planning to
use condoms was reported among female adolescent in the intervention arm than
those in the control arm (p = 0.042). An effect on condom use behaviour was
observed among male adolescent (p = 0.004), but not among female (p = 0.463).
CONCLUSIONS: The PREPARE intervention had an effect in delaying self-reported
sexual initiation among adolescents aged 12-14 in Dar es Salaam Tanzania. The
intervention positively influenced action planning to use condoms for both sexes
and increased actual condom use among male adolescents only. Future interventions
addressing adolescent sexual and reproductive health should focus on impacting
mediators of behaviour change. TRIAL REGISTRATION: Australian New Zealand
Clinical Trials Registry ACTRN12613000900718 , registered on 13 August, 2013.
PMID- 28415974
TI - Evaluation of the association between quantitative mammographic density and
breast cancer occurred in different quadrants.
AB - BACKGROUND: To investigate the relationship between mammographic density measured
in four quadrants of a breast with the location of the occurred cancer. METHODS:
One hundred and ten women diagnosed with unilateral breast cancer that could be
determined in one specific breast quadrant were retrospectively studied. Women
with previous cancer/breast surgery were excluded. The craniocaudal (CC) and
mediolateral oblique (MLO) mammography of the contralateral normal breast were
used to separate a breast into 4 quadrants: Upper-Outer (UO), Upper-Inner (UI),
Lower-Outer (LO), and Lower-Inner (LI). The breast area (BA), dense area (DA),
and percent density (PD) in each quadrant were measured by using the fuzzy-C
means segmentation. The BA, DA, and PD were compared between patients who had
cancer occurring in different quadrants. RESULTS: The upper-outer quadrant had
the highest BA (37 +/- 15 cm2) and DA (7.1 +/- 2.9 cm2), with PD = 20.0 +/- 5.8%.
The order of BA and DA in the 4 separated quadrants were: UO > UI > LO > LI, and
almost all pair-wise comparisons showed significant differences. For tumor
location, 67 women (60.9%) had tumor in UO, 16 (14.5%) in UI, 7 (6.4%) in LO, and
20 (18.2%) in LI quadrant, respectively. The estimated odds and the 95%
confidence limits of tumor development in the UO, UI, LO and LI quadrants were
1.56 (1.06, 2.29), 0.17 (0.10, 0.29), 0.07 (0.03, 0.15), and 0.22 (0.14, 0.36),
respectively. In these 4 groups of women, the order of quadrant BA and DA were
all the same (UO > UI > LO > LI), and there was no significant difference in BA,
DA or PD among them (all p > 0.05). CONCLUSIONS: Breast cancer was most likely to
occur in the UO quadrant, which was also the quadrant with highest BA and DA; but
for women with tumors in other quadrants, the density in that quadrant was not
the highest. Therefore, there was no direct association between quadrant density
and tumor occurrence.
PMID- 28415975
TI - Ka-HOLO Project: a protocol for a randomized controlled trial of a native
cultural dance program for cardiovascular disease prevention in Native Hawaiians.
AB - BACKGROUND: As a major risk factor for cardiovascular and cerebrovascular disease
(CVD), hypertension affects 33% of U.S. adults. Relative to other US races and
ethnicities, Native Hawaiians have a high prevalence of hypertension and are 3 to
4 times more likely to have CVD. Effective, culturally-relevant interventions are
needed to address CVD risk in this population. Investigators of the Ka-HOLO
Project developed a study design to test the efficacy of an intervention that
uses hula, a traditional Hawaiian dance, to increase physical activity and reduce
CVD risk. METHODS: A 2-arm randomized controlled trial with a wait-list control
design will be implemented to test a 6-month intervention based on hula to manage
blood pressure and reduce CVD risk in 250 adult Native Hawaiians with diagnosed
hypertension. Half of the sample will be randomized to each arm, stratified
across multiple study sites. Primary outcomes are reduction in systolic blood
pressure and improvement in CVD risk as measured by the Framingham Risk Score.
Other psychosocial and sociocultural measures will be included to determine
mediators of intervention effects on primary outcomes. Assessments will be
conducted at baseline, 3 months, and 6 months for all participants, and at 12
months for intervention participants only. DISCUSSION: This trial will elucidate
the efficacy of a novel hypertension management program designed to reduce CVD
risk in an indigenous population by using a cultural dance form as its physical
activity component. The results of this culturally-based intervention will have
implications for other indigenous populations globally and will offer a
sustainable, culturally-relevant means of addressing CVD disparities. TRIAL
REGISTRATION: ClinicalTrials.gov: NCT02620709 , registration date November 23,
2015.
PMID- 28415976
TI - SMRT genome assembly corrects reference errors, resolving the genetic basis of
virulence in Mycobacterium tuberculosis.
AB - BACKGROUND: The genetic basis of virulence in Mycobacterium tuberculosis has been
investigated through genome comparisons of virulent (H37Rv) and attenuated
(H37Ra) sister strains. Such analysis, however, relies heavily on the accuracy of
the sequences. While the H37Rv reference genome has had several corrections to
date, that of H37Ra is unmodified since its original publication. RESULTS: Here,
we report the assembly and finishing of the H37Ra genome from single-molecule,
real-time (SMRT) sequencing. Our assembly reveals that the number of H37Ra
specific variants is less than half of what the Sanger-based H37Ra reference
sequence indicates, undermining and, in some cases, invalidating the conclusions
of several studies. PE_PPE family genes, which are intractable to commonly-used
sequencing platforms because of their repetitive and GC-rich nature, are
overrepresented in the set of genes in which all reported H37Ra-specific variants
are contradicted. Further, one of the sequencing errors in H37Ra masks a true
variant in common with the clinical strain CDC1551 which, when considered in the
context of previous work, corresponds to a sequencing error in the H37Rv
reference genome. CONCLUSIONS: Our results constrain the set of genomic
differences possibly affecting virulence by more than half, which focuses
laboratory investigation on pertinent targets and demonstrates the power of SMRT
sequencing for producing high-quality reference genomes.
PMID- 28415977
TI - Perspectives of Frailty and Frailty Screening: Protocol for a Collaborative
Knowledge Translation Approach and Qualitative Study of Stakeholder
Understandings and Experiences.
AB - BACKGROUND: Accompanying the unprecedented growth in the older adult population
worldwide is an increase in the prevalence of frailty, an age-related clinical
state of increased vulnerability to stressor events. This increased vulnerability
results in lower social engagement and quality of life, increased dependency, and
higher rates of morbidity, health service utilization and mortality. Early
identification of frailty is necessary to guide implementation of interventions
to prevent associated functional decline. Consensus is lacking on how to
clinically recognize and manage frailty. It is unknown how healthcare providers
and healthcare consumers understand and perceive frailty, whether or not they
regard frailty as a public health concern; and information on the indirect and
direct experiences of consumer and healthcare provider groups towards frailty are
markedly limited. METHODS: We will conduct a qualitative study of consumer,
practice nurse, general practitioner, emergency department physician, and
orthopedic surgeons' perspectives of frailty and frailty screening in
metropolitan and non-metropolitan South Australia. We will use tailored
combinations of semi-structured interviews and arts-based data collection methods
depending on each stakeholder group, followed by inductive and iterative analysis
of data using qualitative description. DISCUSSION: Using stakeholder driven
approaches to understanding and addressing frailty and frailty screening in
context is critical as the prevalence and burden of frailty is likely to increase
worldwide. We will use the findings from the Perceptions of Frailty and Frailty
Screening study to inform a context-driven identification, implementation and
evaluation of a frailty-screening tool; drive awareness, knowledge, and skills
development strategies across stakeholder groups; and guide future efforts to
embed emerging knowledge about frailty and its management across diverse South
Australian contexts using a collaborative knowledge translation approach. Study
findings will help achieve a coordinated frailty and healthy ageing strategy with
relevance to other jurisdictions in Australia and abroad, and application of the
stakeholder driven approach will help illuminate how its applicability to other
jurisdictions.
PMID- 28415978
TI - Bacterial communities and metabolic activity of faecal cultures from equol
producer and non-producer menopausal women under treatment with soy isoflavones.
AB - BACKGROUND: Isoflavones are polyphenols with estrogenic activity found mainly in
soy and soy-derived products that need to be metabolised in the intestine by the
gut bacteria to be fully active. There is little knowledge about isoflavone
bioconversion and equol production in the human intestine. In this work, we
developed an in vitro anaerobic culture model based on faecal slurries to assess
the impact of isoflavone supplementation on the overall intestinal bacterial
composition changes and associated metabolic transformations. RESULTS: In the
faecal anaerobic batch cultures of this study bioconversion of isoflavones into
equol was possible, suggesting the presence of viable equol-producing bacterial
taxa within the faeces of menopausal women with an equol producer phenotype. The
application of high-throughput DNA sequencing of 16S rRNA gene amplicons revealed
the composition of the faecal cultures to be modified by the addition of
isoflavones, with enrichment of some bacterial gut members associated with the
metabolism of phenolics and/or equol production, such as Collinsella,
Faecalibacterium and members of the Clostridium clusters IV and XIVa. In
addition, the concentration of short-chain fatty acids (SCFAs) detected in the
isoflavone-containing faecal cultures was higher in those inoculated with faecal
slurries from equol-producing women. CONCLUSIONS: This study constitutes the
first step in the development of a faecal culturing system with isoflavones that
would further allow the selection and isolation of intestinal bacterial types
able to metabolize these compounds and produce equol in vitro. Although limited
by the low number of faecal cultures analysed and the inter-individual bacterial
diversity, the in vitro results obtained in this work tend to indicate that soy
isoflavones might provide an alternative energy source for the increase of equol
producing taxa and enhancement of SCFAs production. SCFAs and equol are both
considered pivotal bacterial metabolites in the triggering of intestinal health
related beneficial effects.
PMID- 28415979
TI - Behavioral activation for smoking cessation and mood management following a
cardiac event: results of a pilot randomized controlled trial.
AB - BACKGROUND: Smoking cessation following hospitalization for Acute Coronary
Syndrome (ACS) significantly reduces subsequent mortality. Depressed mood is a
major barrier to cessation post-ACS. Although existing counseling treatments
address smoking and depression independently in ACS patients, no integrated
treatment addresses both. We developed an integrated treatment combining gold
standard cessation counseling with behavioral activation-based mood management;
Behavioral Activation Treatment for Cardiac Smokers (BAT-CS). The purpose of this
pilot randomized controlled trial was to test feasibility, acceptability, and
preliminary efficacy of BAT-CS vs. Standard of Care (SC). METHODS: Participants
were recruited during hospitalization for ACS and were randomly assigned to BAT
CS or SC. The nicotine patch was offered in both conditions. Smoking, mood, and
stress outcomes were collected at end-of-treatment and 24-week follow-up.
RESULTS: Fifty-nine participants (28 BAT-CS, 31 SC) were recruited over 42 weeks,
and assessment completion was above 80% in both conditions. Treatment
acceptability and fidelity were high. At 24 week follow-up adjusted odds ratios
favoring BAT-CS were 1.27 (95% CI: 0.41-3.93) for 7-day point prevalence
abstinence and 1.27 (95% CI: 0.42-3.82) for continuous abstinence. Time to first
smoking lapse was significantly longer in BAT-CS (62.4 vs. 31.8 days, p = 0.03).
At 24-weeks, effect sizes for mood and stress outcomes ranged from eta2partial
of.07-.11, with significant between treatment effects for positive affect,
negative affect, and stress. CONCLUSIONS: The design of this study proved
feasible and acceptable. Results provide preliminary evidence that combining
behavioral activation with standard smoking cessation counseling could be
efficacious for this high risk population. A larger trial with longer follow-up
is warranted. TRIAL REGISTRATION: NCT01964898 . First received by
clinicaltrials.gov October 15, 2013.
PMID- 28415980
TI - The effects of bending speed on the lumbo-pelvic kinematics and movement pattern
during forward bending in people with and without low back pain.
AB - BACKGROUND: Impaired lumbo-pelvic movement in people with low back pain during
bending task has been reported previously. However, the regional mobility and the
pattern of the lumbo-pelvic movement were found to vary across studies. The
inconsistency of the findings may partly be related to variations in the speed at
which the task was executed. This study examined the effects of bending speeds on
the kinematics and the coordination lumbo-pelvic movement during forward bending,
and to compare the performance of individuals with and without low back pain.
METHODS: The angular displacement, velocity and acceleration of the lumbo-pelvic
movement during the repeated forward bending executed at five selected speeds
were acquired using the three dimensional motion tracking system in seventeen
males with low back pain and eighteen males who were asymptomatic. The regional
kinematics and the degree of coordination of the lumbo-pelvic movement during
bending was compared and analysed between two groups. RESULTS: Significantly
compromised performance in velocity and acceleration of the lumbar spine and hip
joint during bending task at various speed levels was shown in back pain group (p
< 0.01). Both groups displayed a high degree of coordination of the lumbo-pelvic
displacement during forward bending executed across the five levels of speed
examined. Significant between-group difference was revealed in the coordination
of the lumbo-pelvic velocity and acceleration (p < 0.01). Asymptomatic group
moved with a progressively higher degree of lumbo-pelvic coordination for
velocity and acceleration while the back pain group adopted a uniform lumbo
pelvic pattern across all the speed levels examined. CONCLUSIONS: The present
findings show that bending speed imposes different levels of demand on the
kinematics and pattern of the lumbo-pelvic movement. The ability to regulate the
lumbo-pelvic movement pattern during the bending task that executed at various
speed levels was shown only in pain-free individuals but not in those with low
back pain. Individuals with low back pain moved with a stereotyped strategy at
their lumbar spine and hip joints. This specific aberrant lumbo-pelvic movement
pattern may have a crucial role in the maintenance of the chronicity in back
pain.
PMID- 28415981
TI - Progress in vaccination towards hepatitis B control and elimination in the Region
of the Americas.
AB - BACKGROUND: Over recent decades, the Region of the Americas has made significant
progress towards hepatitis B elimination. We summarize the countries/territories'
efforts in introducing and implementing hepatitis B (HB) vaccination and in
evaluating its impact on HB virus seroprevalence. METHODS: We collected
information about HB vaccination schedules, coverage estimates, and year of
vaccine introduction from countries/territories reporting to the Pan American
Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF
Joint Reporting Form on Immunization. We obtained additional information
regarding countries/territories vaccination recommendations and strategies
through communications with Expanded Program on Immunization (EPI) managers and
national immunization survey reports. We identified vaccine impact studies
conducted and published in the Americas. RESULTS: As of October 2016, all 51
countries/territories have included infant HB vaccination in their official
immunization schedule. Twenty countries, whose populations represent over 90% of
the Region's births, have included nationwide newborn HB vaccination. We
estimated at 89% and 75%, the regional three-dose series and the birth dose HB
vaccination coverage, respectively, for 2015. The impact evaluations of infant HB
immunization programs in the Region have shown substantial reductions in HB
surface antigen (HBsAg) seroprevalence. CONCLUSION: The achievements of
vaccination programs in the Americas suggest that the elimination of perinatal
and early childhood HB transmission could be feasible in the short-term.
Moreover, the data gathered indicate that the Region may have already achieved
the 2020 WHO goal for HB control.
PMID- 28415982
TI - The treatment of primary mediastinal large B-cell lymphoma: a two decades
monocentric experience with 98 patients.
AB - BACKGROUND: The purpose of this study is to investigate the most suitable first
line approach and the best combination treatment for primary mediastinal large B
cell lymphoma (PMLBCL) as they have been matter of debate for at least two
decades. METHODS: Our single centre experience in the treatment of 98 de novo
PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B
chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy;
30 were irradiated after chemotherapy, although not receiving rituximab and 20
received rituximab without radiotherapy consolidation. Eleven patients received
chemotherapy only. RESULTS: Sixty-one (62.2%) patients achieved a complete
response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial
responders, 21 obtained a complete response after radiotherapy. At the end of
their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial
response (6.1%). Eleven patients relapsed within the first 2 years of follow-up.
The 17-year overall survival is 72.0% (15 patients died); progression-free and
disease-free survival are 67.6% and 88.4%, respectively. A statistically
significant difference in overall and progression-free survival was noted among
treatment groups, although no disease-free survival difference was documented.
CONCLUSIONS: Our data indicate that a third-generation regimen like MACOP-B could
be considered a suitable first-line treatment. Mediastinal consolidation
radiotherapy impacts on survival and complete response rates and remains a good
strategy to convert partial into complete responses. Data suggest that
radiotherapy may be avoided in patients obtaining a complete response after
(immuno)chemotherapy, but this requires confirmation with further ad hoc studies.
PMID- 28415983
TI - Exhaled carbon monoxide: a non-invasive biomarker of short-term exposure to
outdoor air pollution.
AB - BACKGROUND: In urban settings of Africa with rapidly increasing population,
traffic-related air pollution is a major contributor to outdoor air pollution
(OAP). Although OAP has been identified as a leading cause of global morbidity
and mortality, there is however, lack of a simple biomarker to assess levels of
exposure to OAP in resource-poor settings. This study evaluated the role of
exhaled carbon monoxide (exhCO) as a potential biomarker of exposure to ambient
carbon monoxide (ambCO) from OAP. METHODS: This was a descriptive study conducted
among male commercial motorcycle riders in Cotonou - the economic capital of
Benin. The participants' AmbCO was measured using a portable carbon monoxide (CO)
data logger for 8 h during the period of their shift. ExhCO was measured just
before and immediately after their shift (8-h) Participants were asked not to
cook or to smoke during the day of the measurements. Linear regression analysis
was used to assess the association between ambCO and exhCO for the last 2, 4 and
6 h of their shift. RESULTS: Of 170 participants who completed the study, their
mean +/- SD age was 42.2 +/- 8.4 years, and their mean +/- SD daily income was
7.3 +/- 2.7$. Also, 95% of the participants' used solid fuels for cooking and
only 2% had ever smoked. Average exhCO increased by 5.1 ppm at the end of the
shift (p = 0.004). Post-shift exhCO was significantly associated to ambCO, this
association was strongest for the last 2 h of OAP exposure before exhCO
measurement (beta = 0.34, p < 0.001). CONCLUSION: ExhCO level was associated with
recent exposure to ambCO from OAP with measurable increase after 8 h of exposure.
These findings suggest that ExhCO may be a potential biomarker of short-term
exposure to OAP.
PMID- 28415984
TI - Comparison of three different methods for risk adjustment in neonatal medicine.
AB - BACKGROUND: Quality improvement in health care requires identification of areas
in need of improvement by comparing processes and patient outcomes within and
between health care providers. It is critical to adjust for different case-mix
and outcome risks of patient populations but it is currently unclear which
approach has higher validity and how limitations need to be dealt with. Our aim
was to compare 3 approaches towards risk adjustment for 7 different major quality
indicators in neonatal intensive care (21 models). METHODS: We compared an
indirect standardization, logistic regression and multilevel approach. Parameters
for risk adjustment were chosen according to literature and the condition that
they may not depend on processes performed by treating clinics. Predictive
validity was tested using the mean Brier Score and by comparing area under curve
(AUC) using high quality population based data separated into training and
validation sets. Changes in attributional validity were analysed by comparing the
effect of the models on the observed-to-expected ratios of the clinics in
standardized mortality/morbidity ratio charts. RESULTS: Risk adjustment based on
indirect standardization revealed inferior c-statistics but superior Brier scores
for 3 of 7 outcomes. Logistic regression and multilevel modelling were equivalent
to one another. C-statistics revealed that predictive validity was high for 8 and
acceptable for 11 of the 21 models. Yet, the effect of all forms of risk
adjustment on any clinic's comparison with the standard was small, even though
there was clear risk heterogeneity between clinics. CONCLUSIONS: All three
approaches to risk adjustment revealed comparable results. The limited effect of
risk adjustment on clinic comparisons indicates a small case-mix influence on
observed outcomes, but also a limited ability to isolate quality improvement
potential based on risk-adjustment models. Rather than relying on methodological
approaches, we instead recommend that clinics build small collaboratives and
compare their indicators both in risk-adjusted and unadjusted form together. This
allows qualitatively investigating and discussing the residual risk-differences
within networks. The predictive validity should be quantified and reported and
stratification into risk groups should be more widely used to correct for
confounding.
PMID- 28415985
TI - Vitamin D-related gene polymorphism predict treatment response to pegylated
interferon-based therapy in Thai chronic hepatitis C patients.
AB - BACKGROUND: Patients with chronic hepatitis C (HCV) infection have high
prevalence of vitamin D deficiency. Genome-wide association study data has showed
that several genetic variants within vitamin D cascade affect vitamin D function.
This study aimed to determine whether genetic polymorphisms of genes in the
vitamin D pathway are associated with treatment responses to pegylated interferon
(PEG-IFN)-based therapy in patients with chronic HCV infection. METHODS: The
study included 623 Thai patients from 2 university hospitals diagnosed with
chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients
were genotyped for functional variants on vitamin D synthetic pathway including
GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1
(rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained
virologic response (SVR) at 24 weeks following discontinuation of therapy were
identified using a logistic regression analysis. RESULTS: SVR was achieved by
60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In
44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the
DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who
had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele
(59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR
rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG
allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0-1 (OR = 5.00;
95% CI, 2.02-12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95%
CI, 1.03-7.05; P = 0.04) were independent pre-treatment predictors of SVR
following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA <
400,000 IU/ml (OR = 1.96; 95% CI, 1.13-3.39; P = 0.02) was the only independent
predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1
and CYP27B1 were not associated with treatment outcome even in genotype 1 or non
genotype 1 HCV infection. CONCLUSION: The DHCR7 polymorphism may be a pre
treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV
genotype 1 infection.
PMID- 28415986
TI - Detection of CTX-M-15 beta-lactamases in Enterobacteriaceae causing hospital- and
community-acquired urinary tract infections as early as 2004, in Dar es Salaam,
Tanzania.
AB - BACKGROUND: The spread of Extended Spectrum beta-lactamases (ESBLs) among
Enterobacteriaceae and other Gram-Negative pathogens in the community and
hospitals represents a major challenge to combat infections. We conducted a study
to assess the prevalence and genetic makeup of ESBL-type resistance in bacterial
isolates causing community- and hospital-acquired urinary tract infections.
METHODS: A total of 172 isolates of Enterobacteriaceae were collected in Dar es
Salaam, Tanzania, from patients who met criteria of community and hospital
acquired urinary tract infections. We used E-test ESBL strips to test for ESBL
phenotype and PCR and sequencing for detection of ESBL genes. RESULTS: Overall
23.8% (41/172) of all isolates were ESBL-producers. ESBL-producers were more
frequently isolated from hospital-acquired infections (32%, 27/84 than from
community-acquired infections (16%, 14/88, p < 0.05). ESBL-producers showed high
rate of resistance to ciprofloxacin (85.5%), doxycycline (90.2%), gentamicin
(80.5%), nalidixic acid (84.5%), and trimethoprim-sulfamethoxazole (85.4%).
Furthermore, 95% of ESBL-producers were multi-drug resistant compared to 69% of
non-ESBL-producers (p < 0.05). The distribution of ESBL genes were as follows:
29/32 (90.6%) bla CTX-M-15, two bla SHV-12, and one had both bla CTX-M-15 and bla
SHV-12. Of 29 isolates carrying bla CTX-M-15, 69% (20/29) and 31% (9/29) were
hospital and community, respectively. Bla SHV-12 genotypes were only detected in
hospital-acquired infections. CONCLUSION: bla CTX-M-15 is a predominant gene
conferring ESBL-production in Enterobacteriaceae causing both hospital- and
community-acquired infections in Tanzania.
PMID- 28415987
TI - Validity and reliability of fluoroscopy for digital radiography: a new way to
evaluate diaphragmatic mobility.
AB - BACKGROUND: Fluoroscopy is considered the most accurate method to evaluate the
diaphragm, yet most existing methods for measuring diaphragmatic mobility using
fluoroscopy are complex. To assess the validity and reliability of a new
evaluation method of diaphragmatic motion using fluoroscopy by digital
radiography of healthy adults. METHODS: Twenty-six adults were evaluated,
according to the parameters: anthropometry and pulmonary function test. The
evaluation of diaphragm mobility by means of fluoroscopy by digital radiography
method was randomly conducted by two raters (A and B). The Pearson correlation
coefficient and the intraclass correlation coefficient (ICC) were used to assess
the concurrent validity. The inter-rater and intra-rater reliability of the
measurement of diaphragmatic motion was determined using ICC and a confidence
interval of 95%. RESULTS: There was a relationship in the assessment of the
concurrent validity. There was good inter-rater reliability for right
hemidiaphragm mobility and moderate reliability for left hemidiaphragm in the
first assessment. In the second assessment, there was good reliability for the
mobility of both hemidiaphragms. There was good intra-rater reliability in the
mobility of both hemidiaphragms for raters A and B. CONCLUSION: The evaluation of
diaphragmatic motion using fluoroscopy by digital radiography proved to be a
valid and reliable method of healthy adults.
PMID- 28415988
TI - The efficacy and safety of mivacurium in pediatric patients.
AB - BACKGROUND: Mivacurium is the shortest acting nondepolarizing muscle relaxant
currently available; however, the effect of different dosages and injection times
of intravenous mivacurium administration in children of different ages has rarely
been reported. This study was aimed to evaluate the muscle relaxant effects and
safety of different mivacurium dosages administered over different injection
times in pediatric patients. METHODS: Six hundred forty cases of pediatric
patients, aged 2 m-14 years, ASA I or II, were divided into four groups (Groups
A, B, C, D) according to the age class (2-12 m, 13-35 m, 3-6 years and 7-14
years) respectively, also each group were divided into four subgroups by
induction dose (0.15, 0.2 mg/kg in 2-12 m age class; 0.2, 0.25 mg/kg in other
three age classes), and mivacurium injection time (20 s, 40 s), totally 16
subgroups. Neuromuscular transmission was monitored with supramaximal train-of
four stimulation of the ulnar nerve. Radial artery blood (1 ml) was sampled to
quantify plasma histamine concentrations before and 1, 4, and 7 min after
mivacurium injection (P0, P1, P2 and P3). RESULTS: Five hundred sixty-two cases
completed the study. There were no demographic differences within the four
groups. The onset time of 0.2 mg/kg groups in 2-12 m aged patients were shorter
than those of 0.15 mg/kg groups (189 +/- 64 s vs. 220 +/- 73 s, 181 +/- 60 s vs.
213 +/- 71 s, P <0.05), and the recovery times were no statistical differences.
The T1 25% recovery time of 0.2 mg/kg in 3-6 years aged patients was shorter than
that of 0.25 mg/kg group (693 +/- 188 s vs. 800 +/- 206 s, P <0.05). The onset
and recovery times of mivacurium were not different in 13-35 m and 7-14 years
aged patients. The plasma concentrations of histamine at P0, P1, P2 and P3 were
not different within four groups. CONCLUSIONS: The induction dose and injection
time of mivacurium had mostly insignificant effects on onset and recovery times.
The main exception to this was that in 2-12 m aged patients, increasing the dose
of mivacurium from 0.15 to 0.2 mg/kg accelerated the onset time by about 30 s.
Mivacurium produced no significant release of histamine in any age group at the
doses studied. TRIAL REGISTRATION: ClinicalTrials.gov Identifier- NCT02117401 ,
July 14, 2014. (Retrospectively registered).
PMID- 28415989
TI - Evaluation of genotype MTBDRplus VER 2.0 line probe assay for the detection of
MDR-TB in smear positive and negative sputum samples.
AB - BACKGROUND: Multi drug resistant tuberculosis (MDR-TB) poses formidable
challenges to TB control due to its complex diagnostic and treatment challenges
and often associated with a high rate of mortality. Accurate and rapid detection
of MDR-TB is critical for timely initiation of treatment. Line Probe Assay (LPA)
is a qualitative in vitro diagnostic test based on DNA-STRIP technology for the
identification of the M. tuberculosis complex and its resistance to rifampicin
(RMP) and/or isoniazid (INH). Hain Lifescience, GmbH, Germany has improved the
sensitivity of Genotype MTBDRplus VER 2.0 LPA for the detection of MDR-TB; with
the possibility of applying the tool in smear negative sputum samples. METHOD: A
cross sectional study was conducted on 274 presumptive MDR-TB patients referred
to the National TB Reference Laboratory (NTRL), Ethiopian Public Health Institute
(EPHI) who submitted sputum samples for laboratory diagnosis of drug resistant-TB
testing. Seventy-two smear and culture positive samples processed in smear
positive direct LPA category and 197 smear negative sputum samples were processed
for direct LPA. Among the smear negative samples 145 (73.6%) were culture
negative and 26 (13.2%) were culture positive. All specimens were processed using
NALC-NaOH method and ZN smear microscopy done from sediments. Genotype MTBDRplus
VER 2.0 done from processed sputum sediments and the result was compared against
the reference, BACTEC MGIT 960 culture and DST. Sensitivity, specificity, PPV and
NPV of Genotype MTBDRplus VER 2.0 assay was determined and P-value <0.05 was
considered as statistically significant. RESULTS: The sensitivity, specificity,
PPV and NPV of Genotype MTBDRplus VER 2.0 LPA were 96.4, 100, 100 and 96.9%,
respectively for the detection of MDR-TB from direct smear positive sputum
samples. The sensitivity, specificity, PPV and NPV of Genotype MTBDR plus VER 2.0
LPA were 77.8, 97.2, 82.4 and 97.2%, respectively, for the detection of M.
tuberculosis from direct smear negative sputum samples. Fourteen (53.8%) samples
had valid results with LPA among the 26 smear negative culture positive samples.
The remaining 8 (30.8%) and 4 (15.4%) were invalid and negative with LPA,
respectively. The sensitivity and specificity of Genotype MTBDRplus VER 2.0 LPA
were 100% for the detection of MDR-TB among 14 direct smear negative and culture
positive sputum samples. The most common mutations associated with RMP and INH
resistance were S531L and S315TL, respectively. A single rare mutation
(C15T/A16G) was detected for INH resistance. CONCLUSION: The diagnostic
performance of Genotype MTBDRplus VER 2.0 LPA in direct smear positive sputum
sample was highly sensitive and specific for early detection of MDR-TB. However,
the diagnostic performance of this molecular assay in direct smear negative
sputum sample was low and showed a high level of invalid results for detection of
M. tuberculosis and its resistance to RMP and/or INH so it is unlikely to
implement Genotype MTBDRplus VER 2.0 for the detection of MDR-TB in direct smear
negative sample in our routine settings. The sensitivity of the assay should be
improved for detection of MDR-TB in direct smear negative sputum specimens.
PMID- 28415990
TI - Prognostic value of pretreatment standardized uptake value of F-18
fluorodeoxyglucose PET in patients with gastric cancer: a meta-analysis.
AB - BACKGROUND: F-18- fluorodeoxyglucose Positron emission tomography (18FDG-PET) has
been widely used in clinical practice. However, the prognostic value of the
pretreatment standardized uptake value (SUV) for patients with gastric cancer
remains controversial. METHODS: Major databases were systematically searched. The
quality of the included studies was assessed using the Newcastle-Ottawa scale;
the PET protocols were also evaluated. The pooled hazard ratio (HR) for overall
survival (OS) and recurrence-free survival (RFS) were used to estimate the effect
size. Data from the included studies were analyzed using Review Manager Software
version 5.2. RESULTS: Eight studies with 1080 patients were included. The pooled
HR for OS of six studies including 672 patients was 1.72 (95% CI [1.28-2.3], p =
0.0004, I2 = 0%), indicating that patients with high SUVs may have poor
prognosis. The pooled HR for RFS was 1.70 (95% CI [1.20-2.39], p = 0.003, I2 =
0%). Subgroup analysis based on the cutoff values determining method indicated
that the receiver operating characteristic (ROC) method could better define the
cutoff value. Subgroup analysis based on the therapeutic strategies used
subsequently indicated the significant prognostic value of SUV. CONCLUSION: In
conclusion, our meta-analysis indicated that pretreatment SUV in primary lesions
can be an important prognostic factor for overall survival and recurrence-free
survival in patients with gastric cancer. High SUVs may indicate poor prognosis.
PMID- 28415991
TI - Clinical patient registry recruitment and retention: a survey of patients in two
chronic disease registries.
AB - BACKGROUND: The collection of routine clinical data in the setting of research
registries can serve an important role in understanding real world care. However,
relatively little is known about the patient experience in registries, motivating
us to survey patients enrolled in two chronic disease registries. METHODS: We
conducted similar surveys in two disease-based registries based at one academic
medical center in the US. One group of patients with rheumatoid arthritis (RA)
had been enrolled in a registry, and we focused on retention factors. In a second
group of patients with inflammatory bowel disease (IBD) recently enrolled or
considering enrollment, we examined factors that would influence their enrollment
and willingness to answer frequent questionnaires and give biospecimens. The
surveys were analyzed using descriptive statistics and the two cohorts were
compared using nonparametric and chi-square tests. RESULTS: We received 150 (50%)
completed surveys from RA and 169 (63%) from IBD patients. Mean age of subjects
was 62 years in RA and 43 in IBD with more women respondents with RA (83%) than
IBD (62%). The two groups described very similar factors as the top three
motivations for participation: desire to help others, desire to improve care of
own disease, and ease of volunteering. Preferred methods of surveying included
mail, e-mail, but telephone was not favored; age was an important correlate of
this preference. Respondents preferred surveys either every 1-3 months (28.7% RA
and 55.0% IBD) or every 4-6 months (50.7% RA and 29.0% IBD). They differed in the
preference for payment for answering surveys with 68.0% with RA answering that no
payment was necessary but only 36.1% with IBD felt similarly. CONCLUSIONS:
Patients engaged in clinical registries demonstrate a high level of commitment to
improve care and many report a willingness to answer questions relatively
frequently.
PMID- 28415993
TI - Moving to business - changes in physical activity and sedentary behavior after
multilevel intervention in small and medium-size workplaces.
AB - BACKGROUND: Regular physical activity (PA) promotes and excessive sedentary
behavior (SB) deteriorates health. Yet the Finnish working-aged population spends
most of the day sitting. A 1-year Moving To Business (MTB) -intervention
supported small and medium-size workplaces to combat sedentariness. This paper
reports the changes in employees' PA and SB from before MTB (baseline) to 1 year
after baseline (follow-up). METHODS: Twelve workplaces with a total of 396
employees participated. Each workplace nominated a team to promote PA and reduce
SB at organizational, working unit and employee level. The teams were mentored
regionally through meetings, workshop and tools. Changes in PA and SB were
assessed with a questionnaire and an accelerometer. Wald Confidence Interval (Cl)
for a difference of proportions with matched pairs was used in the questionnaire
data (%-points with 95% CI) and linear mixed model in the accelerometer data
(minutes and % of wear-time with 95% CI). RESULTS: The mean age of the
respondents to the questionnaire (N = 296; 75%) was 42.6 (SD 10.9), 64% were
women, 95% had some education after high school, 74% worked in the day shift, 71%
did sedentary work and 51% were overweight. The mean number of actions
implemented in the workplaces was 6.8 and the multilevel approach was fully
applied in 6 workplaces. Based on the questionnaire the time spent in SB
decreased from baseline to follow-up 16% (95% CI -29 to -3) in total and 22% (-41
to -3) at work. The accelerometer showed daily increases of 33.7 min (15.3 to
52.1) and 6.8% (3.1 to 10.4) in total PA, 30.9 min (15.3 to 46.5) and 6.1% (2.9
to 9.2) in light PA and 673 (209 to 1139) more steps at work. Daily SB at work
decreased 44.9 min (-68.0 to -21.8) and 7.6% (-11.9 to -3.2). Daily leisure PA
declined 11.0 min (-24.9 to 2.9) and 3.2% (-6.2 to -0.2). Number of levels or
actions had no effect on changes. CONCLUSIONS: Employees' PA increased and SB
reduced at work during the intervention. At the same time leisure PA decreased
slightly. Workplaces can achieve meaningful changes in employees' PA and SB if
assisted systematically. Controlled studies are needed to confirm the present
findings. TRIAL REGISTRATION: NCT01999205 , registration date 11/01/2013.
PMID- 28415994
TI - A pathological and clinical study of 706 primary tumours of the ovary in the
largest tertiary hospital in Ghana.
AB - BACKGROUND: Ovarian tumours are a leading cause of death in Ghana. Even though
geographical and racial differences exist in the frequency, types and age
distribution of primary ovarian tumours, information about the clinical and
pathological characteristics of ovarian tumours in Ghana and its neighboring
countries is scanty. We determined the frequency, age distribution,
histopathological types and clinical features of primary ovarian tumours
diagnosed at the Korle-Bu Teaching Hospital in Ghana to aid in the management of
patients. METHOD: All pathology records of ovarian tumours diagnosed from January
2001 to December 2010 were reviewed. Histopathologically, tumours were classified
according to the then World Health Organization 1999 classification. Biographical
and clinical data of patients were also collected and entered into Epi-info to
determine the frequency, age distribution and other clinical features of the
types of ovarian tumour. RESULTS: Seven hundred and six ovarian tumours were
studied. Germ cell tumours were the most common (41.9%), with mean age of
occurrence being 30.7 years (SD 12.7), they were dominated by mature teratomas
(39.2%). Surface epithelial tumours were second, and commonly occurred in women
aged 35-44years, 77 (26.8%). Sex cord stromal tumours followed with mean age of
occurrence of 40.2 years (SD 17.9). The most common malignant tumours were
surface epithelial (52.1%) dominated by serous carcinomas with mean age 50.1
years. Most patients (47.7%) presented within 1 month of onset of symptoms,
feeling a lower abdominal mass (38.5%). CONCLUSION: The most common primary
ovarian tumours in this study are Germ cell tumours, dominated by mature
teratomas. Adenocarcinomas are mostly serous and occur in younger women compared
to findings of other Western studies. The single most common malignant ovarian
tumour in children and adolescents is Burkitt lymphoma. Patients who develop
ovarian tumours have no specific symptoms or signs at presentation, to aid early
diagnosis.
PMID- 28415992
TI - Women Epidemiology Lung Cancer (WELCA) study: reproductive, hormonal,
occupational risk factors and biobank.
AB - BACKGROUND: Lung cancer aetiology and clinical aspects have been mainly studied
in men, although specific risk factors probably exist in women. Here we present
the rationale, design and organization of the WELCA study (Women Epidemiology
Lung CAncer) that has been launched to investigate lung cancer in women, focusing
particularly on hormonal and occupational factors. METHODS/DESIGN: WELCA is a
population based case-control study and planned to recruit 1000 cases and 1000
controls in three years, based on study power calculation. Eligible cases are
female patients newly diagnosed with lung cancer, living in Paris and the Ile de
France area and aged up to 75 years. Almost all Parisian pneumology and oncology
clinical departments are involved. The control group is a random sample of the
population living in the same area, frequency-matched on age and additionally
stratified on the distribution of socio-professional categories of women residing
there. After acquisition of written consent, research nurses administer
standardized computer assisted questionnaires to all the subjects in face-to-face
interviews and acquire anthropometric measures. Besides usual socio-demographic
characteristics, information is gathered about menstrual and reproductive
factors, hormonal treatments, lifestyle and leisure characteristics, occupational
history, personal and familial medical history. Biological samples are also
collected, in order to establish a biobank for molecular epidemiology studies.
Molecular characteristics of the tumours will be obtained and patients will be
followed up for five years. DISCUSSION: The WELCA study aims to answer key
questions in lung cancer aetiology and clinical characteristics specifically in
women. The role of hormonal impregnation is investigated, and the interactions
with cigarette smoking or body mass index (BMI) will be analyzed in detail. The
occupational history of the subjects is carefully reconstructed, focusing in
particular on the service sector. The creation of a biobank for collection of
serum, plasma, DNA and tumour tissue will allow the genetic and biochemical
characterization of both the subjets and the tumours. The follow-up of the
patients will help in disentangling the role of hormonal factors and tumour
molecular characteristics in survival.
PMID- 28415995
TI - Type I interferon signaling is required for the APOBEC3/Rfv3-dependent
neutralizing antibody response but not innate retrovirus restriction.
AB - BACKGROUND: APOBEC3/Rfv3 restricts acute Friend retrovirus (FV) infection and
promotes virus-specific neutralizing antibody (NAb) responses. Classical Rfv3
studies utilized FV stocks containing lactate-dehydrogenase elevating virus
(LDV), a potent type I interferon inducer. Previously, we showed that APOBEC3 is
required for the anti-FV activity of exogenous IFN-alpha treatment. Thus, type I
interferon receptor (IFNAR) signaling may be required for the APOBEC3/Rfv3
response. RESULTS: To test if the APOBEC3/Rfv3 response is dependent on type I
IFN signaling, we infected IFNAR knockout versus IFNAR/APOBEC3 double-knockout
mice with FV/LDV or LDV-free FV, and evaluated acute FV infection and subsequent
NAb titers. We show that LDV co-infection and type I IFN signaling are not
required for innate APOBEC3-mediated restriction. By contrast, removal of LDV
and/or type I IFN signaling abrogated the APOBEC3-dependent NAb response.
CONCLUSIONS: APOBEC3 can restrict retroviruses in a type I IFN-independent manner
in vivo. By contrast, the ability of APOBEC3 to promote NAb responses is type I
IFN-dependent. These findings reveal novel insights on the interplay between type
I IFNs and APOBEC3 in vivo that may have implications for augmenting
antiretroviral NAb responses.
PMID- 28415996
TI - Travel and the emergence of high-level drug resistance in Plasmodium falciparum
in southwest Uganda: results from a population-based study.
AB - BACKGROUND: The I164L mutation on the dhfr gene confers high level resistance to
sulfadoxine-pyrimethamine (SP) but it is rare in Africa except in a cluster of
reports where prevalence >10% in highland areas of southwest Uganda and eastern
Rwanda. The occurrence of the dhfr I164L mutation was investigated in community
surveys in this area and examined the relationship to migration. METHODS: A cross
sectional prevalence survey was undertaken in among villages within the catchment
areas of two health facilities in a highland site (Kabale) and a highland fringe
site (Rukungiri) in 2007. Sociodemographic details, including recent migration,
were collected for each person included in the study. A total of 206 Plasmodium
falciparum positive subjects were detected by rapid diagnostic test; 203 in
Rukungiri and 3 in Kabale. Bloodspot samples were taken and were screened for
dhfr I164L. RESULTS: Sequence analysis confirmed the presence of the I164L
mutations in twelve P. falciparum positive samples giving an estimated prevalence
of 8.6% in Rukungiri. Of the three parasite positive samples in Kabale, none had
I164L mutations. Among the twelve I164L positives three were male, ages ranged
from 5 to 90 years of age. None of those with the I164L mutation had travelled in
the 8 weeks prior to the survey, although three were from households from which
at least one household member had travelled during that period. Haplotypes were
determined in non-mixed infections and showed the dhfr I164L mutation occurs in
both as a N51I + S108N + I164L haplotype (n = 2) and N51I + C59R + S108N + I164L
haplotype (n = 5). Genotyping of flanking microsatellite markers showed that the
I164L occurred independently on the triple mutant (N51I, C59R + S108N) and double
mutant (N51I + S108N) background. CONCLUSIONS: There is sustained local
transmission of parasites with the dhfr I164L mutation in Rukungiri and no
evidence to indicate its occurrence is associated with recent travel to highly
resistant neighbouring areas. The emergence of a regional cluster of I164L in SW
Uganda and Rwanda indicates that transmission of I164L is facilitated by strong
drug pressure in low transmission areas potentially catalysed in those areas by
travel and the importation of parasites from relatively higher transmission
settings.
PMID- 28415997
TI - Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF
kappaB/MAPK signaling.
AB - BACKGROUND: Dusuqing granules (DSQ) have been used in the treatment of bacterial
pneumonia clinically, with remarkable benefits. This study was initiated to
explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor
(NF)-kappaB/mitogen-activated protein kinase (MAPK) signaling in bacterial
pneumonia rats. METHODS: Rat model was duplicated with Klebsiella pneumonia by a
one-time intratracheal injection. Rats were randomized into control, model, DSQ
and levofloxacin (LVX) groups. After administrated with appropriate medicines for
7 days, lung tissues were harvested and prepared for pathological analysis, and
interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage
inflammatory protein (MIP)-2 detections. NF-kappaB mRNA was measured by real-time
qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44
were determined by Western blotting. RESULTS: Marked pathological impairments
were observed in model rats, whereas were improved in DSQ group. The cytokines
levels, NF-kappaB mRNA expression and the phosphorylation of P38MAPK, JNK46/54
and ERK42/44 proteins were significantly higher in model group, and were
significantly depressed in DSQ group. CONCLUSION: The protective effects of DSQ
on Klebsiella pneumonia might be attributed to its inactivative effects of NF
kappaB/ MAPK pathway.
PMID- 28415998
TI - Effectiveness of current policing-related mental health interventions in England
and Wales and Crisis Intervention Teams as a future potential model: a systematic
review.
AB - BACKGROUND: Experiencing mental ill health adds a layer of complexity for
individuals in touch with the justice system and for those responsible for
working in the justice service with these individuals, such as frontline police
officers. In England and Wales, there are three commonly used but not necessarily
commonly designed or operated, mental health interventions associated with
policing, Liaison and Diversion, Street Triage and specialist staff embedded in
Police Contact Control Rooms. A fourth US designed model, Crisis Intervention
Teams (CITs), is now attracting some interest in England and Wales, and these
four are to be considered in this review. A fifth intervention, Mental Health
Courts, was trialed but has now been abandoned in England and Wales and so has
been excluded, but remains in use elsewhere. In recent years, there has been an
increase in the level of investment related to these intervention options. This
has largely been without an evidence base being available to aid design,
structure, and consistency of approach. The review will address this gap and
provide a systematic review of each of these options. This will provide a
baseline of research evidence for those who commission and provide services for
individuals experiencing mental ill health and who are in contact with the
justice system. METHODS: Twenty-nine relevant databases and sources have been
selected which will be systematically searched to locate relevant studies. These
studies have to meet the set inclusion criteria which require them to report an
objective outcome measure(s) in respect of offending or mental health outcomes
and to have an experimental or quasi-experimental design including a comparator
group(s) or a pre/post comparison. The review will exclude PhD theses, papers in
non-English languages and papers published prior to 1980. Keywords have been
collected through canvassing experts' opinion, literature review, controlled
vocabulary and reviewing the results of a primary scoping review carried out to
aid the development of the PICO, composed of Population/Participants,
Intervention/Indicator, Comparator/Control, and Outcomes. For the proposed
review, the key elements of the PICO are the following: persons with mental
health problems, symptoms or diagnoses who come into contact with the police;
interventions involving partnership working between police and mental health
nurses and related professionals to divert those with mental health problems away
from criminal justice processes; comparisons with control groups or areas where
such interventions have not been introduced; and outcomes concerning criminal
justice and health outcomes. The results of the searches will be screened using
the set criteria and the selected papers reviewed and analysed to allow findings
regarding these interventions to be reported. DISCUSSION: The objectives of the
review are firstly to identify and report research on the relevant interventions,
nationally and internationally and then secondly to consider, when possible,
which interventions or aspects of those interventions are effective. This is
judged with regard to changes in mental health status or service use and future
offending behaviour. The approaches to be considered have gained a good deal of
support and funding over recent years, and this review will provide a systematic
review of the underpinning research evidence to inform future commissioning,
service design and investment decisions.
PMID- 28415999
TI - Feasibility and effectiveness of a telephone-based social support intervention
for informal caregivers of people with dementia: Study protocol of the TALKING
TIME project.
AB - BACKGROUND: Caring for people with dementia at home requires a significant amount
of time, organization, and commitment. Therefore, informal caregivers, mainly
relatives, of people with dementia often feel a high burden. Although on-site
support groups are known to have positive effects on the subjective well-being
(SWB) and perceived social support of informal caregivers, there are cases in
which relatives have either no time or no opportunity to leave the person alone
or in which there are no support groups nearby. The TALKING TIME project aims to
close this supply gap by providing structured telephone-based support groups in
Germany for the first time. International studies have shown benefits for
informal caregivers. METHODS: The TALKING TIME study is a randomized controlled
trial. The effects of the 3-month TALKING TIME intervention will be compared with
those of a control group without intervention at two time points (baseline = T0,
after 3 months = T1). The control group will receive the TALKING TIME
intervention after T1. With a planned sample size of 88 participants, the study
is powered to detect an estimated effect size of 0.70 for psychological quality
of life, considering an alpha of 0.05 (two-sided), a power of 80%. Caregivers are
informal caregivers who are eligible if they are 18 years of age or older and
have cared for a person with diagnosed dementia for at least four hours, four
days per week, in the past six months. The exclusion criteria are psychiatric
disorders of the informal caregiver. The primary outcome is the mental component
summary of the SF-12 rated by informal caregivers. The secondary outcomes for
informal caregivers are the physical component summary of the SF-12, the
Perceived Social Support Caregiver Scale (SSCS) score, and the Caregiver Reaction
Scale (CRS) score. The secondary outcome for care recipients is the
Neuropsychiatric Inventory (NPI-Q). For the process evaluation, different
quantitative and qualitative data sources will be collected to address reach,
fidelity, dosage and context. DISCUSSION: The results will provide further
information on the effectiveness and optimization of telephone-based support
groups for informal caregivers of people with dementia, which can help guide the
further development of effective telephone-based social support group
interventions. TRIAL REGISTRATION: Clinical Trials: NCT02806583 , June 9, 2016.
PMID- 28416000
TI - Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case
report.
AB - BACKGROUND: Tuberculosis remains a public health problem in developing countries
and is associated with lethal central nervous system complications. Intracranial
tuberculomas occur in 13% of children with neurotuberculosis. Patients with
trisomy 21 have an increased risk for stroke, which usually stems from
cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old
Sudanese boy with trisomy 21 who was presented to our hospital with focal
convulsions and right-sided weakness. The results of neuroimaging and
histopathological examinations were consistent with cerebral tuberculoma. The
patient had a good initial response to antituberculosis drugs and steroids. To
the best of our knowledge, this is the first case report of multiple brain
tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with
trisomy 21 have an increased risk for stroke. Our patient had an exceptional case
of stroke caused by tuberculoma. The present case emphasizes the need to consider
tuberculomas in the differential diagnosis of children with neurological symptoms
living in areas of high tuberculosis incidence.
PMID- 28416001
TI - Assessing environmental factors associated with regional schistosomiasis
prevalence in Anhui Province, Peoples' Republic of China using a geographical
detector method.
AB - BACKGROUND: Schistosomiasis is a water-borne disease caused by trematode worms
belonging to genus Schistosoma, which is prevalent most of the developing world.
Transmission of the disease is usually associated with multiple biological
characteristics and social factors but also factors can play a role. Few studies
have assessed the exact and interactive influence of each factor promoting
schistosomiasis transmission. METHODS: We used a series of different detectors
(i.e., specific detector, risk detector, ecological detector and interaction
detector) to evaluate separate and interactive effects of the environmental
factors on schistosomiasis prevalence. Specifically, (i) specific detector
quantifies the impact of a risk factor on an observed spatial disease pattern,
which were ranked statistically by a value of Power of Determinate (PD)
calculation; (ii) risk detector detects high risk areas of a disease on the
condition that the study area is stratified by a potential risk factor; (iii)
ecological detector explores whether a risk factor is more significant than
another in controlling the spatial pattern of a disease; (iv) interaction
detector probes whether two risk factors when taken together weaken or enhance
one another, or whether they are independent in developing a disease. Infection
data of schistosomiasis based on conventional surveys were obtained at the county
level from the health authorities in Anhui Province, China and used in
combination with information from Chinese weather stations and internationally
available environmental data. RESULTS: The specific detector identified various
factors of potential importance as follows: Proximity to Yangtze River (0.322) >
Land cover (0.285) > sunshine hours (0.256) > population density (0.109) >
altitude (0.090) > the normalized different vegetation index (NDVI) (0.077) >
land surface temperature at daytime (LSTday) (0.007). The risk detector indicated
that areas of schistosomiasis high risk were located within a buffer distance of
50 km from Yangtze River. The ecological detector disclosed that the factors
investigated have significantly different effects. The interaction detector
revealed that interaction between the factors enhanced their main effects in most
cases. CONCLUSION: Proximity to Yangtze River had the strongest effect on
schistosomiasis prevalence followed by land cover and sunshine hours, while the
remaining factors had only weak influence. Interaction between factors played an
even more important role in influencing schistosomiasis prevalence than each
factor on its own. High risk regions influenced by strong interactions need to be
targeted for disease control intervention.
PMID- 28416002
TI - Biological effects of exposure to static electric fields in humans and
vertebrates: a systematic review.
AB - BACKGROUND: High-voltage direct current (HVDC) lines are the technology of choice
for the transport of large amounts of energy over long distances. The operation
of these lines produces static electric fields (EF), but the data reviewed in
previous assessments were not sufficient to assess the need for any environmental
limit. The aim of this systematic review was to update the current state of
research and to evaluate biological effects of static EF. METHODS: Using the
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)
recommendations, we collected and evaluated experimental and epidemiological
studies examining biological effects of exposure to static EF in humans (n = 8)
and vertebrates (n = 40). RESULTS: There is good evidence that humans and animals
are able to perceive the presence of static EF at sufficiently high levels. Hair
movements caused by electrostatic forces may play a major role in this
perception. A large number of studies reported responses of animals (e.g.,
altered metabolic, immunologic or developmental parameters) to a broad range of
static EF strengths as well, but these responses are likely secondary
physiological responses to sensory stimulation. Furthermore, the quality of many
of the studies reporting physiological responses is poor, which raises concerns
about confounding. CONCLUSION: The weight of the evidence from the literature
reviewed did not indicate that static EF have adverse biological effects in
humans or animals. The evidence strongly supported the role of superficial
sensory stimulation of hair and skin as the basis for perception of the field, as
well as reported indirect behavioral and physiological responses. Physical
considerations also preclude any direct effect of static EF on internal
physiology, and reports that some physiological processes are affected in minor
ways may be explained by other factors. While this literature does not support a
level of concern about biological effects of exposure to static EF, the
conditions that affect thresholds for human detection and possible annoyance at
suprathreshold levels should be investigated.
PMID- 28416003
TI - Characterization and risk estimate of cancer in patients with primary Sjogren
syndrome.
AB - BACKGROUND: The purpose of this study is to characterize the risk of cancer in a
large cohort of patients with primary Sjogren syndrome (SjS). METHODS: We had
analyzed the development of cancer in 1300 consecutive patients fulfilling the
2002 SjS classification criteria. The baseline clinical and immunological
characteristics and systemic activity (ESSDAI scores) were assessed at diagnosis
as predictors of cancer using Cox proportional hazards regression analysis
adjusted for age at diagnosis and gender. The sex-and age-specific standardized
incidence ratios (SIR) of cancer were estimated from 2012 Spanish mortality data.
RESULTS: After a mean follow-up of 91 months, 127 (9.8%) patients developed 133
cancers. The most frequent type of cancer was B-cell lymphoma (including 27 MALT
and 19 non-MALT B-cell lymphomas). Systemic activity at diagnosis of primary SjS
correlated with the risk of hematological neoplasia and cryoglobulins with a high
risk of either B-cell or non-B-cell lymphoma subtypes. Patients with cytopenias
had a high risk of non-MALT B-cell and non-B-cell cancer, while those with low C3
levels had a high risk of MALT lymphomas and those with monoclonal gammopathy and
low C4 levels had a high risk of non-MALT lymphomas. The estimated SIR for solid
cancer was 1.13 and 11.02 for hematological cancer. SIRs for specific cancers
were 36.17 for multiple myeloma and immunoproliferative diseases, 19.41 for
Hodgkin lymphoma, 6.04 for other non-Hodgkin lymphomas, 5.17 for thyroid cancer,
4.81 for cancers of the lip and oral cavity, and 2.53 for stomach cancer.
CONCLUSIONS: One third of cancers developed by patients with primary SjS are B
cell lymphomas. The prognostic factors identified at SjS diagnosis differed
according to the subtype of B-cell lymphoma developed. Primary SjS is also
associated with the development of some non-hematological cancers (thyroid, oral
cavity, and stomach).
PMID- 28416005
TI - Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers
with immune-mediated rheumatic disease.
AB - Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by
immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic
stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear
antibodies (ANA), which are also commonly present in the autoimmune disease
systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD
indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute
phase protein, is a quantitative marker of inflammation for many diseases and is
used for diagnosing and monitoring systemic inflammation in both humans and dogs.
However, in human SLE, CRP concentrations are often elevated but correlate poorly
with disease activity; they can be low in individual patients with active
disease. The aim of the study was to investigate CRP in a group of NSDTRs with
the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would
be increased in dogs with IMRD compared to healthy dogs, but that the increase
would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs
and 19 healthy control NSDTRs using two different canine-specific CRP assays.
Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but
the concentrations were below the clinical decision limit for systemic
inflammation for most of the IMRD dogs. These results indicate that CRP
concentrations were increased in dogs with IMRD and ANA, but the increase was
mild, similar to what has been observed in human SLE.
PMID- 28416004
TI - Clinical study of children with Takayasu arteritis: a retrospective study from a
single center in China.
AB - BACKGROUND: Delayed diagnosis of childhood Takayasu arteritis (TA) is common due
to its atypical symptoms. The objective of the present study was to summarize the
clinical features of childhood TA to raise awareness and improve management.
METHODS: Eleven children diagnosed with TA at our hospital were enrolled.
Clinical information, diagnosis, treatment, and outcome were then examined
retrospectively. The Pediatric Vasculitis Activity Score (PVAS) and the Indian
Takayasu Clinical Activity Score (ITAS2010) were used to assess disease activity.
RESULTS: Male-to-female ratio was 4:7. The mean age was 9.4 (1.4-14) years and
the average time to diagnosis was 40.6 days (12-90 days). All patients suffered
from hypertension and few had immunologic abnormalities. Two patients had low
levels of autoantibodies and one had elevated immunoglobulin E levels. Aberrant
(elevated) laboratory parameters included erythrocyte sedimentation rate (ESR)
(9/10 patients, 90.0%), protein excretion (8/9 patients, 88.9%), renin
angiotensin-aldosterone system (RAAS) activity (5/5 patients, 100.0%), and serum
lipid levels (3/5 patients, 60%). The common onset patterns were headache with
convulsions (27.2%) and kidney damage (27.2%). The abdominal aorta (81.8%) and
renal artery (72.7%) were the most commonly involved vessels. At presentation,
the mean PVAS and ITAS2010 scores were 12.1 (6-26)/63 and 9.7 (5-14)/57,
respectively. All patients were treated with glucocorticoids and antihypertensive
agents; two underwent renal artery stent placement. CONCLUSION: The diagnosis of
TA should be considered in patients with pediatric hypertension and high
expression of inflammatory markers or abnormal urine results. Doppler
ultrasonography of major vessels may be helpful. PVAS and ITAS2010 both help to
evaluate disease activity, and the PVAS is recommended for patients with kidney
damage. Glucocorticoid and antihypertensive agents are effective. Interventional
therapy can be an option for patients with persistent hypertension.
PMID- 28416006
TI - Leishmania major large RAB GTPase is highly immunogenic in individuals immune to
cutaneous and visceral leishmaniasis.
AB - BACKGROUND: We previously identified a Leishmania (L.) major large RAB GTPase
(LmlRAB), a new atypical RAB GTPase protein. It is highly conserved in Leishmania
species while displaying low level of homology with mammalian homologues.
Leishmania small RAB GTPases proteins have been involved in regulation of
exocytic and endocytic pathways whereas the role of large RAB GTPases proteins
has not been characterized yet. We report here the immunogenicity of both
recombinant rLmlRAB and rLmlRABC, in individuals with immunity against L. major
or L. infantum. METHODS: PBMC were isolated from individuals cured of L. major
(CCLm) or from healthy individuals. The latter were subdivided into high or low
IFN-gamma responders. Healthy high IFN-gamma responders, considered as
asymptomatics, were living in an endemic area for L. major (HHRLm) or L. infantum
(HHRLi). Healthy low IFN-gamma responders (HLR) were considered as naive
controls. Cells from all volunteers were stimulated with rLmlRAB or rLmlRABC.
Cytokines were analysed by CBA and ELISA and phenotypes of IFN-gamma-producing
cells were analysed by flow cytometry. RESULTS: Both rLmlRAB and rLmlRABC induced
high significant levels of IFN-gamma in CCLm, HHRLm and HHRLi groups. Phenotype
analysis of rLmlRAB and rLmlRABC-stimulated T cells in CCLm individuals showed a
significant increase in the percentage of specific IFN-gamma-producing CD4+ and
CD8+ T cells. rLmlRAB induced significant granzyme B levels in CCLm and HHRLm.
Low but significant granzyme B levels were detected in naive group. IL-10 was
detected in immune and naive individuals. CONCLUSION: We showed that rLmlRAB
protein and its divergent carboxy-terminal part induced a predominant Th1
response in individuals immune to L. major or L. infantum. Our results suggest
that rLmlRAB and rLmlRABC proteins are potential cross-species vaccine candidates
against cutaneous and visceral leishmaniasis.
PMID- 28416007
TI - Disseminated alveolar echinococcosis resembling metastatic malignancy: a case
report.
AB - BACKGROUND: Alveolar echinococcosis is a potentially lethal zoonosis caused by
larval forms of the tapeworm Echinococcus multilocularis. Humans are aberrant
intermediate hosts who become infected by ingestion of egg-contaminated food or
water or via physical contact with domestic or wild animals that carry the
parasite in their small intestine. In humans, the disease usually affects the
liver and can spread to other organs causing metastatic infiltration. In this
report, we describe an advanced presentation of human alveolar echinococcosis
mimicking metastatic malignancy. CASE PRESENTATION: A 62-year-old white woman was
evaluated for fever, jaundice, and abdominal pain, associated with significant
weight loss. She lived in a rural area in Switzerland and used to eat wild forest
fruits and mushrooms. She owned cats that used to hunt rodents. On physical
examination, she appeared severely ill with cachexia, altered mental status,
jaundice, and massive hepatomegaly. Laboratory tests showed cholestasis with
preserved liver function. An abdominal computed tomography scan showed an
enlarged liver with a huge cystic mass in the right lobe extending into the left
lobe, infiltrating her hepatic hilum, causing intrahepatic bile duct dilation and
occlusion of her right portal vein. A chest computed tomography scan showed
multiple calcified bilateral pulmonary nodules. Her clinical and radiological
presentation resembled an advanced neoplastic disease. Serologic tests for
Echinococcus multilocularis were positive. The diagnosis of alveolar
echinococcosis was established on her past history of exposure, imaging, and
serology results. CONCLUSIONS: Clinical presentation and radiologic imaging
findings of disseminated alveolar echinococcosis can mimic metastatic malignancy,
and diagnosis can be challenging in atypically advanced cases. As the incidence
of human alveolar echinococcosis appears to be increasing in Europe and
Switzerland, physicians should be aware of alveolar echinococcosis, its
epidemiology, and its clinical features.
PMID- 28416008
TI - A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian
perspective.
AB - Physicians often come across with cases of vitamin K antagonists-dependent
coagulopathy for reasons such as accidental use of the vitamin K antagonists
(VKA), excessive administration of prescribed anticoagulants of indirect action
or not reported administration of vitamin K antagonists due to memory impairment
and/or other mental disorders, even deliberate use thereof (attempt to murder or
suicide). Rodenticide-poisoning (coumarins, warfarins) via food or occupational
accidents are difficult to diagnose. This article discusses different types of
acquired vitamin K-dependent coagulopathy. Differential diagnosis is primarily
based on patient statements before additional causes of vitamin K deficiency are
explored. Even when pathological vitamin K deficiency is not determined,
appropriate and urgent medical treatment is necessary: administration of fresh
frozen plasma or concentrated factors of the prothrombin complex, administration
of vitamin K remedies along with symptomatic therapy. With early diagnosis and
prescription of appropriate therapy, prognosis is favorable. Reasons for vitamin
K antagonists-dependent coagulopathy cases.
PMID- 28416009
TI - Use of Lot quality assurance sampling surveys to evaluate community health worker
performance in rural Zambia: a case of Luangwa district.
AB - BACKGROUND: The Better Health Outcomes through Mentoring and Assessment (BHOMA)
project is a cluster randomized controlled trial aimed at reducing age
standardized mortality rates in three rural districts through involvement of
Community Health Workers (CHWs), Traditional Birth Attendants (TBAs), and
Neighborhood Health Committees (NHCs). CHWs conduct quarterly surveys on all
households using a questionnaire that captures key health events occurring within
their catchment population. In order to validate contact with households, we
utilize the Lot Quality Assurance Sampling (LQAS) methodology. In this study, we
report experiences of applying the LQAS approach to monitor performance of CHWs
in Luangwa District. METHODS: Between April 2011 and December 2013, seven health
facilities in Luangwa district were enrolled into the BHOMA project. The health
facility catchment areas were divided into 33 geographic zones. Quality assurance
was performed each quarter by randomly selecting zones representing about 90% of
enrolled catchment areas from which 19 households per zone where also randomly
identified. The surveys were conducted by CHW supervisors who had been trained on
using the LQAS questionnaire. Information collected included household identity
number (ID), whether the CHW visited the household, duration of the most recent
visit, and what health information was discussed during the CHW visit. The
threshold for success was set at 75% household outreach by CHWs in each zone.
RESULTS: There are 4,616 total households in the 33 zones. This yielded a target
of 32,212 household visits by community health workers during the 7 survey
rounds. Based on the set cutoff point for passing the surveys (at least 75%
households confirmed as visited), only one team of CHWs at Luangwa high school
failed to reach the target during round 1 of the surveys; all the teams otherwise
registered successful visits in all the surveys. CONCLUSIONS: We have employed
the LQAS methodology for assurance that quarterly surveys were successfully done.
This methodology proved helpful in identifying poorly performing CHWs and could
be useful for evaluating CHW performance in other areas. TRIAL REGISTRATION:
Identifier: NCT01942278 . Date of Registration: September 2013.
PMID- 28416010
TI - The effect of thymoquinone coating on adhesive properties of polypropylene mesh.
AB - BACKGROUND: An incisional hernia is a common complication following abdominal
surgery. Polypropylene mesh is frequently used in the repair of such defects and
has nearly become the standard surgical treatment modality. Though they are very
effective in reducing recurrence, mesh materials exhibit a strong stimulating
effect for intraabdominal adhesion. The thymoquinone (TQ) extracted from Nigella
sativa seeds has potential medical properties. TQ has anti-inflammatory,
antioxidant and antibacterial properties. The aim of this study is to coat
polypropylene mesh with TQ in order to investigate the effect of surface
modification on intraabdominal adhesions. METHODS: TQ-coated polypropylene mesh
material was tested for cytotoxicity, contact angle, surface spectroscopy, TQ
content, sterility, and electron microscopic surface properties. An experimental
incisional hernia model was created in study groups, each consisting of 12 female
Wistar rats. The defect was closed with uncoated mesh in control group, with
polylactic acid (PLA) coated mesh and PLA-TQ coated mesh in study groups.
Adhesion scores and histopathologic properties were evaluated after sacrifice on
postoperative 21th day. RESULTS: Granuloma formation, lymphocyte and
polymorphonuclear leukocyte infiltration, histiocyte fibroblast and giant cell
formation, capillary infiltration, collagen content were significantly reduced in
the PLA-TQ coated mesh group (p < 0.05). Though not statistically significant,
likely due to the limited number of study animals, adhesion formation was also
reduced in the PLA-TQ coated mesh group (p: 0.067). CONCLUSION: TQ coated mesh is
shown to reduce adhesion formation and TQ is a promising coating material for
mesh surface modification.
PMID- 28416011
TI - Which learning activities enhance physiotherapy practice? A systematic review
protocol of quantitative and qualitative studies.
AB - BACKGROUND: Learning activities are fundamental for the development of expertise
in physiotherapy practice. Continuing professional development (CPD) encompasses
formal and informal learning activities undertaken by physiotherapists.
Identifying the most efficient and effective learning activities is essential to
enable the profession to assimilate research findings and improve clinical skills
to ensure the most efficacious care for clients. To date, systematic reviews on
the effectiveness of CPD provide limited guidance on the most efficacious models
of professional development for physiotherapists. The aim of this systematic
review is to evaluate which learning activities enhance physiotherapy practice.
METHODS: A search of Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied
Health Literature (CINAHL), PsycINFO (Psychological Abstracts), PEDro, Cochrane
Library, AMED and Educational Resources and Information Center (ERIC) will be
completed. Citation searching and reference list searching will be undertaken to
locate additional studies. Quantitative and qualitative studies will be included
if they examine the impact of learning activities on clinician's behaviour,
attitude, knowledge, beliefs, skills, self-efficacy, work satisfaction and
patient outcomes. Risk of bias will be assessed by two independent researchers.
Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and
Confidence in the Evidence from Reviews of Qualitative research (CERQual) will be
used to synthesise results where a meta-analysis is possible. Where a meta
analysis is not possible, a narrative synthesis will be conducted. SYSTEMATIC
REVIEW REGISTRATION: PROSPERO CRD42016050157.
PMID- 28416012
TI - Congenital Cytomegalovirus infection: advances and challenges in diagnosis,
prevention and treatment.
AB - Cytomegalovirus (CMV) is the most frequent cause of congenital infection
worldwide, with an estimated incidence in developing countries of 0.6-0.7% of all
live births. The burden of disease related to congenital CMV in substantial, as
it is the leading non-genetic cause of sensorineural hearing loss and an
important cause of neurodevelopmental disabilities in children. Despite its
clinical significance, congenital CMV infection often goes undetected because the
majority of infected infants are asymptomatic at birth and screening programs
have not been substantially implemented. Other than behavioral measures,
effective interventions aimed at the prevention of maternal infection and of
mother-to-child transmission are lacking. Due to a convergence of recent advances
in both diagnostic and therapeutic strategies in infants with congenital CMV,
though, the field likely will be changing rapidly over just the next few years.
Specifically, a highly-sensitive screening test with high throughput potential
has been developed, and treatment of infants symptomatically infected with
congenital CMV has proven to be well-tolerated and effective in improving long
term hearing and neurodevelopmental outcomes.This review highlights the clinical
importance of congenital CMV infection, the developments in laboratory
diagnostics, and the benefits of antiviral therapy. It also identifies the global
efforts still required in the prevention of maternal infection and in the
optimization of antiviral therapy to further reduce the burden of congenital CMV
disease.
PMID- 28416013
TI - No seasonal variation in physical activity of Han Chinese living in Beijing.
AB - BACKGROUND: Physical activity (PA) is widely acknowledged to be beneficial to
health and wellbeing, and is potentially influenced by a variety of environmental
factors such as ambient temperature, weather conditions and air pollution levels.
Since these factors vary seasonally, physical activity participation may also
respond seasonally. Current population studies to profile physical activity often
sample individuals only once, and this may result in biased estimates if there is
strong seasonal variation. METHODS: We conducted a study of 40 Han Chinese adults
living in Beijing using GT3X accelerometers. We measured PA levels every two
months across a complete year, while simultaneously monitoring ambient
temperatures and air pollution levels. Average hourly vector magnitude (VM) and
percentage time spent at each PA intensity (sedentary to light, moderate,
vigorous and very vigorous) were measured. General Linear models (GLMs) were used
to explore the effects of time of day, temperature and PM 2.5 levels on PA. One
way ANOVA was used to test whether there were seasonal differences in body weight
and body fatness. RESULTS: The main factors influencing activity levels were the
time of day and individual characteristics including age and body fatness, but
there was no significant difference between the months. In addition, there was no
significant impact of either ambient temperature or air pollution levels (PM2.5).
There were also no significant differences over the year in the time spent at
sedentary-light, moderate and very vigorous PA levels, but for vigorous PA level
which occupied less than 0.5% daily physical activity, both month and individual
were significant factors. CONCLUSIONS: The relatively constant pattern of urban
daily life, independent of time of year, may override the potential impacts of
environmental factors that would be anticipated to impact PA levels. These
subjects did not specifically avoid activity coincident with elevated air
pollution levels (PM2.5). Single week long measurements of physical activity
could provide a representative measurement of the physical active levels in this
population.
PMID- 28416015
TI - Costs and health-related quality of life in Alpha-1-Antitrypsin Deficient COPD
patients.
AB - BACKGROUND: Alpha-1-Antitrypsin Deficiency (AATD) is an economically unexplored
genetic disease. METHODS: Direct and indirect costs (based on self-reported
information on healthcare utilization) and health-related quality of life (HRQL,
as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients
(106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without
AATD participating in the COSYCONET COPD cohort. The medication costs of AT were
excluded from all analyses to reveal differences associated with morbidity
profiles. The association of AATD (with/without AT) with costs or HRQL was
examined using generalized linear regression modelling (GLM) adjusting for age,
sex, GOLD grade, BMI, smoking status, education and comorbidities. RESULTS:
Adjusted mean direct annual costs were ?6,099 in AATD patients without AT, ?7,117
in AATD patients with AT (excluding costs for AT), and ?7,460 in COPD patients
without AATD. AATD with AT was significantly associated with higher outpatient
(+273%) but lower inpatient (-35%) and medication costs (-10%, disregarding AT)
compared with COPD patients without AATD. There were no significant differences
between groups regarding indirect costs and HRQL. CONCLUSION: Apart from AT
costs, AATD patients tended to have lower, though not significant, overall costs
and similar HRQL compared to COPD patients without AATD. AT was not associated
with lower costs or higher HRQL. TRIAL REGISTRATION: NCT01245933.
PMID- 28416016
TI - Variation in rates of ICU readmissions and post-ICU in-hospital mortality and
their association with ICU discharge practices.
AB - BACKGROUND: Variation in intensive care unit (ICU) readmissions and in-hospital
mortality after ICU discharge may indicate potential for improvement and could be
explained by ICU discharge practices. Our objective was threefold: (1) describe
variation in rates of ICU readmissions within 48 h and post-ICU in-hospital
mortality, (2) describe ICU discharge practices in Dutch hospitals, and (3) study
the association between rates of ICU readmissions within 48 h and post-ICU in
hospital mortality and ICU discharge practices. METHODS: We analysed data on
42,040 admissions to 82 (91.1%) Dutch ICUs in 2011 from the Dutch National
Intensive Care Evaluation (NICE) registry to describe variation in standardized
ICU readmission and post-ICU mortality rates using funnel-plots. We send a
questionnaire to all Dutch ICUs. 75 ICUs responded and their questionnaire data
could be linked to 38,498 admissions in the NICE registry. Generalized estimation
equations analyses were used to study the association between ICU readmissions
and post-ICU mortality rates and the identified discharge practices, i.e. (1) ICU
discharge criteria; (2) bed managers; (3) early discharge planning; (4) step-down
facilities; (5) medication reconciliation; (6) verbal and written handover; (7)
monitoring of post-ICU patients; and (8) consulting ICU nurses. In all analyses,
the outcomes were corrected for patient-related confounding factors. RESULTS: The
standardized rate of ICU readmissions varied between 0.14 and 2.67 and 20.8% of
the hospitals fell outside the 95% control limits and 3.6% outside the 99.8%
control limits. The standardized rate of post-ICU mortality varied between 0.07
and 2.07 and 17.1% of the hospitals fell outside the 95% control limits and 4.9%
outside the 99.8% control limits. We could not demonstrate an association between
the eight ICU discharge practices and rates of ICU readmissions or post-ICU in
hospital mortality. Implementing a higher number of ICU discharge practices was
also not associated with better patient outcomes. CONCLUSIONS: We found both
variation in patient outcomes and variation in ICU discharge practices between
ICUs. However, we found no association between discharge practices and rates of
ICU readmissions or post-ICU mortality. Further research is necessary to find
factors, which may influence these patient outcomes, in order to improve quality
of care.
PMID- 28416017
TI - Patient complexity and genotype-phenotype correlations in biliary atresia: a
cross-sectional analysis.
AB - BACKGROUND: Biliary Atresia (BA) is rare and genetically complex, and the
pathogenesis is elusive. The disease course is variable and can represent
heterogeneity, which hinders effective disease management. Deciphering the BA
phenotypic variance is a priority in clinics and can be achieved by the
integrative analysis of genotype and phenotype. We aim to explore the BA
phenotypic features and to delineate the source of its variance. METHODS: The
study is a cross-sectional observational study collating with case/control
association analysis. One-hundred-and-eighty-one type III non-syndromic BA
patients and 431 controls were included for case-control association tests,
including 89 patients (47.19% males, born June 15th, 1981 to September 17th,
2007) have detailed clinical records with follow-up of the disease course (median
~17.2 years). BA-association genes from the genome-wide gene-based association
test on common genetic variants (CV) and rare copy-number-variants (CNVs) from
the genome-wide survey, the later comprise only CNVs > 100 kb and found in the BA
patients but not in the local population (N = 1,381) or the database (N =
11,943). Hereby comorbidity is defined as a chronic disease that affects the BA
patients but has no known relationship with BA or with the BA treatment. We
examined genotype-phenotype correlations of CNVs, connectivity of these novel
variants with BA-associated CVs, and their role in the BA candidate gene network.
RESULTS: Of the 89 patients, 41.57% have comorbidities, including autoimmune
allergic disorders (22.47%). They carried 29 BA-private CNVs, including 3 CNVs
underpinning the carriers' immunity comorbidity and one JAG1 micro-deletion. The
BA-CNV-intersected genes (N = 102) and the CV-tagged genes (N = 103) were both
enriched with immune-inflammatory pathway genes (FDR q < 0.20), and the two gene
sets were interconnected (permutation p = 0.039). The molecular network
representing CVs and rare-CNV association genes fit into a core/periphery
structure, the immune genes and their related modules are found at the coherence
core of all connections, suggesting its dominant role in the BA pathogenesis
pathway. CONCLUSIONS: The study highlights a patient-complexity phenomenon as a
novel BA phenotypic feature, which is underpinned by rare-CNVs that biologically
converge with CVs into the immune-inflammatory pathway and drives the BA
occurrence and the likely BA association with immune diseases in clinics.
PMID- 28416018
TI - Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from
children with diffuse midline glioma.
AB - Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are
highly morbid glial neoplasms of the thalamus or brainstem that typically arise
in young children and are not surgically resectable. These tumors are
characterized by a high rate of histone H3 mutation, resulting in replacement of
lysine 27 with methionine (K27M) in genes encoding H3 variants H3.3 (H3F3A) and
H3.1 (HIST1H3B). Detection of these gain-of-function mutations has clinical
utility, as they are associated with distinct tumor biology and clinical
outcomes. Given the paucity of tumor tissue available for molecular analysis and
relative morbidity of midline tumor biopsy, CSF-derived tumor DNA from patients
with diffuse midline glioma may serve as a viable alternative for clinical
detection of histone H3 mutation. We demonstrate the feasibility of two
strategies to detect H3 mutations in CSF-derived tumor DNA from children with
brain tumors (n = 11) via either targeted Sanger sequencing of H3F3A and
HIST1H3B, or H3F3A c.83 A > T detection via nested PCR with mutation-specific
primers. Of the six CSF specimens from children with diffuse midline glioma in
our cohort, tumor DNA sufficient in quantity and quality for analysis was
isolated from five (83%), with H3.3K27M detected in four (66.7%). In addition,
H3.3G34V was identified in tumor DNA from a patient with supratentorial
glioblastoma. Test sensitivity (87.5%) and specificity (100%) was validated via
immunohistochemical staining and Sanger sequencing in available matched tumor
tissue specimens (n = 8). Our results indicate that histone H3 gene mutation is
detectable in CSF-derived tumor DNA from children with brain tumors, including
diffuse midline glioma, and suggest the feasibility of "liquid biopsy" in lieu
of, or to complement, tissue diagnosis, which may prove valuable for
stratification to targeted therapies and monitoring treatment response.
PMID- 28416020
TI - Patient- and family-centered performance measures focused on actionable processes
of care for persistent and chronic critical illness: protocol for a systematic
review.
AB - BACKGROUND: Approximately 5 to 10% of critically ill patients transition from
acute critical illness to a state of persistent and in some cases chronic
critical illness. These patients have unique and complex needs that require a
change in the clinical management plan and overall goals of care to a focus on
rehabilitation, symptom relief, discharge planning, and in some cases, end-of
life care. However, existing indicators and measures of care quality, and tools
such as checklists, that foster implementation of best practices, may not be
sufficiently inclusive in terms of actionable processes of care relevant to these
patients. Therefore, the aim of this systematic review is to identify the
processes of care, performance measures, quality indicators, and outcomes
including reports of patient/family experience described in the current evidence
base relevant to patients with persistent or chronic critical illness and their
family members. METHODS: Two authors will independently search from inception to
November 2016: MEDLINE, Embase, CINAHL, Web of Science, the Cochrane Library,
PROSPERO, the Joanna Briggs Institute and the International Clinical Trials
Registry Platform. We will include all study designs except case series/reports
of <10 patients describing their study population (aged 18 years and older) using
terms such as persistent critical illness, chronic critical illness, and
prolonged mechanical ventilation. Two authors will independently perform data
extraction and complete risk of bias assessment. Our primary outcome is to
determine actionable processes of care and interventions deemed relevant to
patients experiencing persistent or chronic critical illness and their family
members. Secondary outcomes include (1) performance measures and quality
indicators considered relevant to our population of interest and (2) themes
related to patient and family experience. DISCUSSION: We will use our systematic
review findings, with data from patient, family member and clinician interviews,
and a subsequent consensus building process to inform the development of quality
metrics and tools to measure processes of care, outcomes and experience for
patients experiencing persistent or chronic critical illness and their family
members. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016052715.
PMID- 28416021
TI - Effects of GABAB receptors in the insula on recognition memory observed with
intellicage.
AB - BACKGROUND: Insular function has gradually become a topic of intense study in
cognitive research. Recognition memory is a commonly studied type of memory in
memory research. GABABR has been shown to be closely related to memory formation.
In the present study, we used intellicage, which is a new intelligent behavioural
test system, and a bilateral drug microinjection technique to inject into the
bilateral insula, to examine the relationship between GABABR and recognition
memory. METHODS: Male Sprague-Dawley rats were randomly divided into control,
Sham, Nacl, baclofen and CGP35348 groups. Different testing procedures were
employed using intellicage to detect changes in rat recognition memory. The
expression of GABABR (GB1, GB2) in the insula of rats was determined by
immunofluorescence and western blotting at the protein level. In addition, the
expression of GABABR (GB1, GB2) was detected by RT-PCR at the mRNA level.
RESULTS: The results of the intellicage test showed that recognition memory was
impaired in terms of position learning, punitive learning and punitive reversal
learning by using baclofen and CGP35348. In position reversal learning, no
significant differences were found in terms of cognitive memory ability between
the control groups and the CGP and baclofen groups. Immunofluorescence data
showed GABABR (GB1, GB2) expression in the insula, while data from RT-PCR and
western blot analysis demonstrated that the relative expression of GB1 and GB2
was significantly increased in the baclofen group compared with the control
groups. In the CGP35348 group, the expression of GB1 and GB2 was significantly
decreased, but there was no significant difference in GB1 or GB2 expression in
the control groups. CONCLUSIONS: GABABR expression in the insula plays an
important role in the formation of recognition memory in rats.
PMID- 28416019
TI - A window into living with an undiagnosed disease: illness narratives from the
Undiagnosed Diseases Network.
AB - BACKGROUND: Patients' stories of their illnesses help bridge the divide between
patients and providers, facilitating more humane medical care. Illness narratives
have been classified into three types: restitution (expectation of recovery),
chaos (suffering and loss), and quest (unexpected positive effect from illness).
Undiagnosed patients have unique illness experiences and obtaining their
narratives would provide insights into the medical and emotional impact of living
with an undiagnosed illness. Adults and children with undiagnosed diseases apply
to be evaluated by the Undiagnosed Diseases Network (UDN). Written illness
narratives from 40 UDN applicants, including 20 adult probands who applied for
themselves and 20 parents who applied for their children, were analyzed for: 1)
narrative content and 2) narrative type. RESULTS: Narrative content: could be
grouped into three themes: 1) Expectations of the UDN: the majority felt they had
no further healthcare options and hoped the UDN would provide them with a
diagnosis, with the adults expecting to return to their previously healthy life
and the parents wanting information to manage their child's healthcare. 2)
Personal medical information: the narratives reported worsening of symptoms and
some offered opinions regarding the cause of their illness. The proband
narratives had few objective findings, while parental narratives had detailed
objective information. 3) Experiences related to living with their undiagnosed
illness: frustration at being undiagnosed was expressed. The adults felt they had
to provide validation of their symptoms to providers, given the lack of objective
findings. The parents worried that something relevant to their child's management
was being overlooked. Narrative type: All the narratives were of the chaos type,
but for different reasons, with the probands describing loss and suffering and
the parents expressing fear for their child's future. The parental narratives
also had elements of restitution and quest, with acceptance of "a new normal",
and an emphasis on the positive aspects of their child's illness which was absent
from the probands. CONCLUSIONS: These narratives illustrate the chaos that
coexists with being undiagnosed. The differences between the proband and parental
narratives suggest that these two groups have different needs that need to be
considered during their evaluation and management.
PMID- 28416022
TI - Specific or general exercise strategy for subacromial impingement syndrome-does
it matter? A systematic literature review and meta analysis.
AB - BACKGROUND: Exercise is frequently suggested as a treatment option for patients
presenting with symptoms of subacromial impingement syndrome. Some would argue
implementing a specific exercise strategy with special focus on correction of
kinematic deficits would be superior to general exercise strategy. There is
however a lack of evidence comparing such exercise strategies to determine which
is the most effective in the treatment of subacromial impingement syndrome. The
aim of this review is to evaluate whether implementing specific exercise
strategies involving resistive exercises are more effective than a general
exercise strategy for the treatment of patients with subacromial impingement
syndrome. METHODS: Randomized controlled trials were identified through an
electronic search on PubMed/MEDLINE, EMBASE, Cochrane Central Register of
Controlled Trials, Web of Science and PEDro. In addition, article reference lists
and Clinicaltrials.gov were searched. Studies were considered eligible if they
included interventions with resistive specific exercises as compared to general
resistance exercise. Four reviewers assessed risk of bias and methodological
quality guided by Cochrane recommendations. Results were synthesised
qualitatively or quantitatively, where appropriate. RESULTS: Six randomized
controlled trials were included with 231 participants who experienced symptoms of
subacromial impingement syndrome. Four studies evaluated the effectiveness of
specific scapular exercise strategy and two studies evaluated the effectiveness
of specific proprioceptive strategy. Five studies were of moderate quality and
one study was of low quality. No consistent statistical significant differences
in outcomes between treatment groups were reported in the studies. Standardized
mean difference (SMD) for pain was SMD -0.19 (95% CI -0.61, 0.22) and SMD 0.30
(95% CI -0.16, 0.76) for function. CONCLUSIONS: There is insufficient evidence to
support or refute the effectiveness of specific resistive exercise strategies in
the rehabilitation of subacromial impingement syndrome. More high quality
research is needed to accurately assess this. This review provides suggestions on
how to improve the methodological design of future studies in this area.
PMID- 28416024
TI - Polymorphism in male genitalia of Aedes (Ochlerotatus) scapularis Rondani, 1848.
AB - Morphology of male genitalia of culicids is generally species-specific and often
used as a taxonomic marker. However, some characters of the male genitalia vary
intraspecifically and are not taxonomically diagnostic. This might be the case of
Aedes scapularis, a Neotropical culicid with vector competence for arboviruses
and filarial worms. Males of this species may or not present a retrorse process
(RP) in the genitalic claspette filaments, which led authors to suspect that this
variance might be indicative of population divergence or incipient speciation
process. This suspicion has not been investigated hitherto and it is not known if
there are variable patterns of RPs. We hypothesized that the presence of the RP
varies intraspecifically in Ae. scapularis and then we statistically evaluated
the variability of this character in a single population. To this study the
genitalia of 73 males of Ae. scapularis were prepared, and their RPs were
meristically quantified and categorized according to the phenotypes observed. We
noted that the presence or RPs is a polymorphic character because it varied inter
and intra-individually. The presence of a single RP on each claspette filament
was the predominant pattern (77%), but absent or multiple RPs in each filament
were also found either in bilateral symmetry or asymmetry. Thus, we conclude that
the presence of RPs owing to its high variability is not indicative of
populational divergence or diagnostic of species complex within Ae. scapularis.
PMID- 28416025
TI - Healthcare innovation and patent law's 'pharmaceutical privilege': is there a
pharmaceutical privilege? And if so, should we remove it?
AB - This article reviews current trends in patent claims regarding personalised,
stratified and precision medicine. These trends are not particularly well
understood by policymakers, even less by the public, and are quite recent.
Consequently, their implications for the public interest have hardly been thought
out. Some see personalised and other secondary drug patent claims as promoting
better targeted treatment. Others are inclined to see them as ?manifestations of
'evergreening' whereby companies are, in some cases quite cynically, trying to
extend market monopolies in old products or creating new monopolies based on
supposedly improved versions of such earlier drugs. The article claims that the
relaxation of 'novelty' is a privilege unavailable to inventions in other fields
and that on balance the patent system does privilege this industry and that no
adequate case has yet been made thus far to prove the public benefits overall.
PMID- 28416023
TI - The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry:
design, rationale, and characteristics of patients enrolled in the first 12
months.
AB - BACKGROUND: Herein we describe the history, design, and rationale of the new
Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and
present the characteristics of patients with juvenile idiopathic arthritis (JIA)
enrolled in the first 12 months of operation. METHODS: The CARRA Registry began
prospectively collecting data in the United States and Canada in July 2015 to
evaluate the safety of therapeutic agents in persons with childhood-onset
rheumatic disease, initially restricted to JIA. Secondary objectives include the
evaluation of disease outcomes and their associations with medication use and
other factors. Data are collected every 6 months and include clinical
assessments, detailed medication use, patient-reported outcomes, and safety
events. Follow-up is planned for at least 10 years for each participant and is
facilitated by a telephone call center. RESULTS: As of July 2016, 1192 patients
with JIA were enrolled in the CARRA Registry at 49 clinical sites. At enrollment,
their median age was 12.4 years old and median disease duration was 2.6 years.
Owing to preferential enrollment, patients with systemic JIA (13%) and with a
polyarticular course (75%) were over-represented compared to patients in typical
clinical practice. Approximately 49% were currently using biologic agents and
ever use of oral glucocorticoids was common (47%). The CARRA Registry provides
safety surveillance data to pharmaceutical companies to satisfy their regulatory
requirements, and several independently-funded sub-studies that use the Registry
infrastructure are underway. CONCLUSION: The new CARRA Registry successfully
enrolled nearly 1200 participants with JIA in the first 12 months of its
operation. Sustainable funding has been secured from multiple sources. The CARRA
Registry may serve as a model for the study of other uncommon diseases.
PMID- 28416026
TI - Evaluation of a pilot service to facilitate discharge of patients with stable
long-term mental health needs from secondary to primary care: the role of Primary
Care Mental Health Specialists.
AB - : Aim We aimed to evaluate a pilot service to facilitate discharge of patients
with stable long-term mental health needs from secondary to primary care.
BACKGROUND: Patients with stable long-term mental health conditions are often not
discharged from secondary mental health services when no longer needed due to
insufficient systems and processes to enable safe, effective, recovery-focussed
treatment and support. The Primary Care Mental Health Specialist (PCMHS) Service
was developed to address this gap; new PCMHS posts were introduced to act as a
conduit for patients being discharged from secondary care and a single point of
referral back into secondary care, should it be required. The two-year pilot,
across six Clinical Commissioning Groups in South East England, began in March
2013. METHODS: Interviews were conducted with all PCMHS employed in the pilot
service (n=13) and a sample of service users (n=12). The views of professionals
working alongside the service, including GPs, Psychiatrists and Mental Health
Nurses, were captured using a brief online questionnaire (n=50). Time and
Activity Recording Sheets were used to capture data required for economic
analysis. Findings Our findings indicate that the service is working well from
the perspective of patients; staff employed within the service and professionals
working alongside the service. Patients described the service as a 'safety net'
they could fall back on in case of difficulties, whereas staff used the analogy
of a 'bridge' to describe the way the service improved communication and
collaboration between the various professionals and organisations involved in the
patient's care. Improvements in well-being were seen to result from increased
support for those transitioning from secondary to primary care, a more pro-active
approach to relapse prevention and increased engagement in daily activities. Each
PCMHS covered 36 patients in a one-month period, with a unit cost of L73.01 per
patient.
PMID- 28416027
TI - Pharmacological and non-pharmacological treatment preferences of healthcare
professionals and proxies for challenging behaviors in patients with dementia.
AB - BACKGROUND: Prescribing antipsychotics to patients with neuropsychiatric symptoms
is a matter of concern. Physicians have to make treatment decisions for patients
with dementia together with proxies and/or nurses. However, it is unknown whether
physicians, nurses, and proxies' treatment preferences are aligned; hence this
study. METHODS: Sixteen treatment attributes were selected to elicit the
preferences of physicians and nurses. Ten of these attributes were used for the
proxies. Preferences were estimated using a case-1 Best-Worst-Scaling design;
respondents are asked to select the best and worst attribute on being presented
with a hypothetical patient with dementia demonstrating neuropsychiatric
symptoms. The treatments offered are: antipsychotic treatment or non
pharmaceutical regimens. RESULTS: The questionnaire was filled in by 41
physicians, 81 nurses, and 59 proxies. The non-pharmacological treatment option
was chosen by 52% of the proxies and 71% of the physicians and nurses. The
respondents who chose antipsychotics rated the aspects "fastest result" and "most
effective" as important. Physicians ranked "experience with antipsychotics" as an
important aspect for prescribing antipsychotics. Only the proxies rated the
aspect "having a low negative effect on the patient" as important. The nurses and
elderly care physicians who chose the non-pharmaceutical treatment ranked
"appropriateness" and "of little burden to the patient" as important aspects.
CONCLUSIONS: While doctors and nurses prefer non-pharmacological interventions,
proxies indicated a preference for pharmacological treatment because of the
immediate effect. However, physicians follow treatment guidelines and nurses and
proxies rely on the physician's recommendations. We suggest physicians should be
sensitive to these differences.
PMID- 28416028
TI - Attitudes and perceptions of pregnant women with CHD: results of a single-site
survey.
AB - : Introduction CHD occurs in about 1% of the United States population, and is now
the most common cardiac condition affecting women during pregnancy. METHODS: An
anonymous, single-site, cross-sectional, 50-question survey was performed at a
national Adult Congenital Heart Disease conference to assess the level of
knowledge, attitudes, and perceptions regarding cardiac care during pregnancy in
women with CHD. RESULTS: A total of 77 women completed the survey. Among them,
50% (n=39) had moderate and 38% (n=29) had severely complex disease; 30% (n=23)
of women were told that pregnancy was contraindicated given their underlying
cardiac condition. Almost two-thirds (n=50) report being categorised as high risk
for adverse cardiovascular events. During pregnancy, 84% (n=65) preferred their
cardiologist to have trained in adult CHD, 44% (n=34) were satisfied with adult
cardiologists, and 36% (n=28) with paediatric cardiologists. Only 48% (n=37) were
aware that a fetal echocardiogram was indicated. Only 35% (n=27) discussed modes
of delivery with their providers, and 70% (n=54) preferred their prenatal
cardiology visits at an adult hospital. Up to 85% (n=64) of them had discussed
contraception with their cardiologists, and 72% (n=56) felt they needed high-risk
maternal-fetal medicine to be involved with their care. CONCLUSIONS: Despite
seeking medical care, these pregnant women did not have a full understanding of
their condition and their cardiovascular risk during pregnancy. On the basis of
these results, further efforts are needed to improve the knowledge, attitudes,
and perceptions of women with CHD in relation to their cardiac and obstetric
management during pregnancy.
PMID- 28416029
TI - The health outcomes of human offspring conceived by assisted reproductive
technologies (ART).
AB - Concerns have been raised about the health and development of children conceived
by assisted reproductive technologies (ART) since 1978. Controversially, ART has
been linked with adverse obstetric and perinatal outcomes, an increased risk of
birth defects, cancers, and growth and development disorders. Emerging evidence
suggests that ART treatment may also predispose individuals to an increased risk
of chronic ageing related diseases such as obesity, type 2 diabetes and
cardiovascular disease. This review will summarize the available evidence on the
short-term and long-term health outcomes of ART singletons, as multiple
pregnancies after multiple embryos transfer, are associated with low birth weight
and preterm delivery, which can separately increase risk of adverse postnatal
outcomes, and impact long-term health. We will also examine the potential factors
that may contribute to these health risks, and discuss underlying mechanisms,
including epigenetic changes that may occur during the preimplantation period and
reprogram development in utero, and adult health, later in life. Lastly, this
review will consider the future directions with the view to optimize the long
term health of ART children.
PMID- 28416030
TI - Prevalence, neurobiology, and treatments for apathy in prodromal dementia.
AB - BACKGROUND: Apathy, characterized by diminished motivation, is a highly prevalent
neuropsychiatric symptom in dementia. However, there is a substantial knowledge
gap with regard to prevalence rates, neurobiological underpinnings, and effective
treatments for apathy in pre-dementia states, including mild cognitive impairment
(MCI) and mild behavioral impairment (MBI). METHODS: We conducted a comprehensive
literature search using MEDLINE, Embase, and PsycINFO databases to identify
available research on apathy in prodromal dementia. RESULTS: Apathy has
consistently been detected in individuals with MCI with varying prevalence rates,
and only recently has literature discussed the prevalence of apathy in MBI. Few
pharmacological treatments have been utilized for apathy, with galantamine and
risperidone showing mild reductions in apathetic behaviors. Non-pharmacological
interventions in prodromal dementia are beginning to be explored and show
promise, but few studies have replicated those results. DISCUSSION: More
comprehensive guidelines for diagnosing apathy and further research investigating
neurobiological mechanisms of apathy in MCI and MBI are required in order to
effectively treat apathetic patients in prodromal dementia.
PMID- 28416031
TI - Behavioral and psychological symptoms of dementia: prevalence, symptom groups and
their correlates in community-based older adults with dementia in Singapore.
AB - BACKGROUND: This study assessed the prevalence and factor structure of behavioral
and psychological symptoms of dementia (BPSD) in a community-based sample of
older adults with dementia and identified their correlates. METHODS: Data
collected from 399 Singapore residents with dementia aged 60 years and above,
interviewed along with a family/friend during a national survey, were used for
this analysis. Neuropsychiatric Inventory Questionnaire assessed older adults'
BPSD. Other data included socio-demographics, dementia severity, cognition,
chronic physical conditions, disability, and caregivers' burden. Exploratory
factor analysis assessed BPSD sub-groups, factor scores of which were used to
identify socio-demographic, and clinical correlates. RESULTS: Prevalence of BPSD
was 67.9% and 30% of the population had experienced three or more BPSD in the
past month. Two distinct and moderately correlated symptom groups representing
"psychosis and behavior dysregulation" and "mood disturbance and restlessness"
were identified. As factor scores for both the groups increased with older age,
poor cognition and caregiver burden, the former was also related to being never
married and having no formal education. CONCLUSIONS: Study provides evidence of
two distinct groups of BPSD and their important correlates. Clinicians treating
BPSD should consider their age and cognitive impairment and be cognizant of their
caregivers' burden.
PMID- 28416032
TI - Physiological, metabolic and transcriptional postnatal phenotypes of in vitro
fertilization (IVF) in the mouse.
AB - Approximately 1-4% of children today are conceived using assisted reproductive
technologies (ARTs), including in vitro fertilization (IVF). IVF is considered
safe and the great majority of these children are healthy, yet there is
increasing physiological and molecular evidence from animal models that ART is
associated with postnatal metabolic and cardiovascular alterations. Understanding
the mechanisms underlying these changes and determining whether they have
biological significance is of paramount importance for optimizing the design of
culture conditions and improving the health of ART children across the life
course. In this review, we examine the evidence of molecular changes present in
adult tissues of rodent offspring generated by preimplantation manipulation of
gametes and embryos. Although embryo manipulation in vitro can induce common
transcriptional effects in the blastocyst, transcriptional and metabolomic
signatures in adult IVF tissues are largely tissue-specific. However, there is
pervasive evidence of oxidative stress and metabolic dysfunction, indicating a
lasting effect of IVF on molecular physiology.
PMID- 28416033
TI - Pharmacological treatment of mixed states.
AB - Mixed states in bipolar disorder have been neglected, and the data concerning
treatment of these conditions have been relatively obscure. To address this, we
systematically reviewed published pharmacological treatment data for "mixed
states/episodes" in mood disorders, including "with mixed features" in DSM-5. We
searched PubMed, MEDLINE, The Cochrane Library, clinicaltrials.gov, and
controlled-trials.com (with different combinations of the following keywords:
"mixed states/features," "bipolar," "depressive symptoms/bipolar depression,"
"manic symptoms," "treatment," "DSM-5") through to October 2016. We applied a
quality-of-evidence approach: first-degree evidence=randomized placebo-controlled
studies of pharmacological interventions used as monotherapy; second-degree
evidence=a similar design in the absence of a placebo or of a combination therapy
as a comparative group; third-degree evidence=case reports, case series, and
reviews of published studies. We found very few primary double-blind, placebo
controlled studies on the treatment of mixed states: the preponderance of
available data derives from subgroup analysis performed on studies that
originally involved manic patients. Future research should study the effects of
treatments in mixed states defined using current criteria.
PMID- 28416034
TI - COHABITATION AND UNION DISSOLUTION IN CENTRAL UGANDA: DIFFERENCES BETWEEN
COHABITORS AND NON-COHABITORS.
AB - The aim of this paper was to establish whether the differences in the risks of
union dissolution between cohabitors and non-cohabitors in Uganda have converged
over time using event history data. Data were collected in 2013 from 1200 women
in central Uganda using retrospective methods. Of these, 839 provided information
on three types of first union: women who married directly (without first
cohabiting), those who married following cohabitation and those who were still
cohabiting. The data were analysed using decrement lifetable analysis. Though the
analysis indicated a small difference in the timing of first union dissolution
for women who married directly, no evidence was found that the difference in the
risk of union dissolution between cohabitors and non-cohabitors had converged
over the 9-year period following first union. Women's union/marriage status,
number of living children in a union, parental union status and birth cohort were
found to significantly influence the timing of union dissolution. Overall, the
rate of union dissolution was fairly high, regardless of type of union.
PMID- 28416035
TI - Measuring the Autocorrelation Function of Nanoscale Three-Dimensional Density
Distribution in Individual Cells Using Scanning Transmission Electron Microscopy,
Atomic Force Microscopy, and a New Deconvolution Algorithm.
AB - Essentially all biological processes are highly dependent on the nanoscale
architecture of the cellular components where these processes take place.
Statistical measures, such as the autocorrelation function (ACF) of the three
dimensional (3D) mass-density distribution, are widely used to characterize
cellular nanostructure. However, conventional methods of reconstruction of the
deterministic 3D mass-density distribution, from which these statistical measures
can be calculated, have been inadequate for thick biological structures, such as
whole cells, due to the conflict between the need for nanoscale resolution and
its inverse relationship with thickness after conventional tomographic
reconstruction. To tackle the problem, we have developed a robust method to
calculate the ACF of the 3D mass-density distribution without tomography.
Assuming the biological mass distribution is isotropic, our method allows for
accurate statistical characterization of the 3D mass-density distribution by ACF
with two data sets: a single projection image by scanning transmission electron
microscopy and a thickness map by atomic force microscopy. Here we present
validation of the ACF reconstruction algorithm, as well as its application to
calculate the statistics of the 3D distribution of mass-density in a region
containing the nucleus of an entire mammalian cell. This method may provide
important insights into architectural changes that accompany cellular processes.
PMID- 28416036
TI - Exploring dementia management attitudes in primary care: a key informant survey
to primary care physicians in 25 European countries.
AB - BACKGROUND: Strategies for the involvement of primary care in the management of
patients with presumed or diagnosed dementia are heterogeneous across Europe. We
wanted to explore attitudes of primary care physicians (PCPs) when managing
dementia: (i) the most popular cognitive tests, (ii) who had the right to
initiate or continue cholinesterase inhibitor or memantine treatment, and (iii)
the relationship between the permissiveness of these rules/guidelines and PCP's
approach in the dementia investigations and assessment. METHODS: Key informant
survey. SETTING: Primary care practices across 25 European countries. SUBJECTS:
Four hundred forty-five PCPs responded to a self-administered questionnaire. Two
step cluster analysis was performed using characteristics of the informants and
the responses to the survey. MAIN OUTCOME MEASURES: Two by two contingency tables
with odds ratios and 95% confidence intervals were used to assess the association
between categorical variables. A multinomial logistic regression model was used
to assess the association of multiple variables (age class, gender, and perceived
prescription rules) with the PCPs' attitude of "trying to establish a diagnosis
of dementia on their own." RESULTS: Discrepancies between rules/guidelines and
attitudes to dementia management was found in many countries. There was a strong
association between the authorization to prescribe dementia drugs and pursuing
dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28-5.23). CONCLUSIONS:
Differing regulations about who does what in dementia management seemed to affect
PCP's engagement in dementia investigations and assessment. PCPs who were allowed
to prescribe dementia drugs also claimed higher engagement in dementia work-up
than PCPs who were not allowed to prescribe.
PMID- 28416037
TI - Birth weight, biological maturation and obesity in adolescents: a mediation
analysis.
AB - This study was aimed to investigate associations between birth weight and
multiple adiposity indicators in youth, and to examine potential mediating
effects by biological maturation. This was a school-based study involving 981
Brazilian adolescents aged between 10 and 17 years. Birth weight was reported
retrospectively by mothers. Maturation was estimated by age of peak height
velocity. Adiposity indicators included body mass index (BMI), waist
circumference and percent body fat estimated from triceps and subscapular
skinfolds. Multilevel mediation analyses were performed using the Sobel test,
adjusted for chronological age, gestational age, cardiorespiratory fitness and
socio-economic status. Except for body fat in girls, biological maturation partly
or fully mediated (P<0.05) positive relationships between birth weight with all
other obesity indicators in both sexes with their respective values of indirect
effects with 95% confidence intervals: BMI [boys: 0.44 (0.06-0.82); girls: 0.38
(0.13-0.64)], waist circumference [boys: 1.14 (0.22-2.05); girls: 0.87 (0.26
1.48)] and body fat [boys: 0.60 (0.13-1.07)]. To conclude, birth weight is
associated with elevated obesity risk in adolescence and biological maturation
seems to at least partly mediate this relationship.
PMID- 28416038
TI - The effects of fermentation and enzymatic treatment of pea on nutrient
digestibility and growth performance of broilers.
AB - The present study examined the impacts of native, fermented or enzymatically
treated peas (Pisum sativum L.) inclusion in broiler diets, on growth performance
and nutrient digestibility. For the fermentation process, Madonna pea was mixed
with water (1/1) containing 2.57*108 Bacillus subtilis (GalliPro(r)) spores/kg
pea and then, incubated for 48 h at 30 degrees C. For the enzymatic treatment
process, the used water for dough production contained three enzymes, AlphaGalTM
(alpha-galactosidase), RONOZYME(r) ProAct and VP (protease and pectinases
respectively - DSM, Switzerland) and the pea dough incubated for 24 h at 30
degrees C. Nine corn-wheat-soybean diets were formulated by supplying 10%, 20%
and 30% of the required CP with either native, fermented or enzymatically treated
peas. Performance was recorded weekly and at the end of the experiment (day 35),
apparent ileal digestibility (AID) of CP, amino acids (AA), crude fat, starch,
Ca, P and K were determined. Data were subjected to ANOVA using GLM procedure
with a 3*3 factorial arrangement of treatments. Both processes reduced alpha
galactosides, phytate, trypsin inhibitor activity and resistant starch in peas.
Increasing levels of pea products up to 300 g/kg diet, reduced BW gain and feed
intake (P?0.05). Broilers fed diets containing enzymatically treated pea had the
best feed conversion ratio at day 35. Different types of pea product and their
inclusion levels had no effect on AID of all nutrients. The interaction between
type of the pea products and inclusion levels was significant for AID of starch.
For native pea diets, 10% group showed similar AID of starch to 20% native pea
but it had higher AID than 30% native pea. For fermented and enzymatically
treated groups, all three levels displayed similar AID of starch. In conclusion,
enzymatic treatment and fermentation could improve the nutritional quality of
pea. Inclusion of enzymatically treated pea in broiler diets could improve
broiler performance compared with other pea products while, it displayed neither
positive nor negative impact on nutrient digestibility. The present findings
indicate the feasibility of these processes, particularly enzymatic treatment,
for improving the nutritional quality of pea as a protein source for broiler
nutrition.
PMID- 28416039
TI - Pig cognitive bias affects the conversion of muscle into meat by antioxidant and
autophagy mechanisms.
AB - Slaughter is a crucial step in the meat production chain that could induce
psychological stress on each animal, resulting in a physiological response that
can differ among individuals. The aim of this study was to investigate the
relationship between an animal's emotional state, the subsequent psychological
stress at slaughter and the cellular damage as an effect. In all, 36 entire male
pigs were reared at an experimental farm and a cognitive bias test was used to
classify them into positive bias (PB) or negative bias (NB) groups depending on
their decision-making capabilities. Half of the animals, slaughtered in the same
batch, were used for a complete study of biomarkers of stress, including brain
neurotransmitters and some muscle biomarkers of oxidative stress. After
slaughter, specific brain areas were excised and the levels of catecholamines
(noradrenaline (NA) and dopamine (DA)) and indoleamines (5-hydroxyindoleacetic
acid and serotonin (5HT)) were analyzed. In addition, muscle proteasome activity
(20S), antioxidant defence (total antioxidant activity (TAA)), oxidative damage
(lipid peroxidation (LPO)) and autophagy biomarkers (Beclin-1, microtubule
associated protein I light chain 3 (LC3-I) and LC3-II) were monitored during
early postmortem maturation (0 to 24 h). Compared with PB animals, NB pigs were
more susceptible to stress, showing higher 5HT levels (P<0.01) in the hippocampus
and lower DA (P<0.001) in the pre-frontal cortex. Furthermore, NB pigs had more
intense proteolytic processes and triggered primary muscle cell survival
mechanisms immediately after slaughter (0 h postmortem), thus showing higher TAA
(P<0.001) and earlier proteasome activity (P<0.001) and autophagy (Beclin-1,
P<0.05; LC3-II/LC3-I, P<0.001) than PB pigs, in order to counteract the induced
increase in oxidative stress, that was significantly higher in the muscle of NB
pigs at 0 h postmortem (LPO, P<0.001). Our study is the first to demonstrate that
pig's cognitive bias influences the animal's susceptibility to stress and has
important effects on the postmortem muscle metabolism, particularly on the cell
antioxidant defences and the autophagy onset. These results expand the current
knowledge regarding biomarkers of animal welfare and highlight the potential use
of biomarkers of the proteasome, the autophagy (Beclin-1, LC3-II/LC3-I ratio) and
the muscle antioxidant defence (TAA, LPO) for detection of peri-slaughter stress.
PMID- 28416040
TI - EFFECT OF EARLY SEXUAL DEBUT ON HIGH SCHOOL COMPLETION IN SOUTH AFRICA.
AB - Early sexual debut is of major concern because it is a correlate for health and
economic shocks experienced in adulthood. In South Africa, this concern has
provided impetus for research directed at the HIV and AIDS epidemic, teenage
pregnancy and the effect of adolescent sexual behaviour on persistence in school.
Of interest to the present study is high school completion, which is a well
established empirical barometer of adult socioeconomic opportunities. Using data
from the five waves of the Cape Area Panel Study (CAPS), this paper examines the
association between sexual behaviours initiated in pre- and early adolescence and
high school completion rates. The CAPS study is a longitudinal survey that was
designed to investigate young people's (aged 14-22 years) educational attainment
and sexual behaviours in Cape Town, South Africa. The sample was constituted from
3213 individuals who had initiated sex during their teenage years and the
analysis was undertaken when the youngest cohort was aged 21, an age at which
they should have completed high school if they were on time. Logistic regression
models were fitted separately for males and females. Overall, the results reveal
that early sexual debut is correlated with long-term negative educational
outcomes. Individuals who experience early sexual debut are less likely to
complete high school than their counterparts who make their sexual debut later on
in life. This effect is worse for Africans, who also disproportionately have an
earlier sexual debut than other race groups. Apart from race however, the
findings also reinforce the effect of other demographic factors on high school
completion, namely, place of residence and family socioeconomic status as
measured by parental education and household income. Hence, early sexual debut
adds another layer of inequality and worsens the plight of Africans, females,
those living in rural areas and those who come from low-income families.
PMID- 28416041
TI - Child-targeted fast-food television advertising exposure is linked with fast-food
intake among pre-school children.
AB - OBJECTIVE: To determine whether exposure to child-targeted fast-food (FF)
television (TV) advertising is associated with children's FF intake in a non
experimental setting. DESIGN: Cross-sectional survey conducted April-December
2013. Parents reported their pre-school child's TV viewing time, channels watched
and past-week FF consumption. Responses were combined with a list of FF
commercials (ads) aired on children's TV channels during the same period to
calculate children's exposure to child-targeted TV ads for the following chain FF
restaurants: McDonald's, Subway and Wendy's (MSW). SETTING: Paediatric and Women,
Infants, and Children (WIC) clinics in New Hampshire, USA. SUBJECTS: Parents (n
548) with a child of pre-school age. RESULTS: Children's mean age was 4.4 years;
43.2 % ate MSW in the past week. Among the 40.8 % exposed to MSW ads, 23.3 % had
low, 34.2 % moderate and 42.5 % high exposure. McDonald's accounted for over 70 %
of children's MSW ad exposure and consumption. Children's MSW consumption was
significantly associated with their ad exposure, but not overall TV viewing time.
After adjusting for demographics, socio-economic status and other screen time,
moderate MSW ad exposure was associated with a 31 % (95 % CI 1.12, 1.53) increase
and high MSW ad exposure with a 26 % (95 % CI 1.13, 1.41) increase in the
likelihood of consuming MSW in the past week. Further adjustment for parent FF
consumption did not change the findings substantially. CONCLUSIONS: Exposure to
child-targeted FF TV advertising is positively associated with FF consumption
among children of pre-school age, highlighting the vulnerability of young
children to persuasive advertising and supporting recommendations to limit child
directed FF marketing.
PMID- 28416042
TI - Earthquakes, Fuel Crisis, Power Outages, and Health Care in Nepal: Implications
for the Future.
AB - Earthquakes are a major natural calamity with pervasive effects on human life and
nature. Similar effects are mimicked by man-made disasters such as fuel crises
and power outages in developing countries. Natural and man-made disasters can
cause intangible human suffering and often leave scars of lifelong psychosocial
damage. Lessons from these disasters are frequently not implemented. The main
objective of this study was to review the effects of the 2015 earthquakes, fuel
crisis, and power outages on the health services of Nepal and formulate
recommendations for the future. The impacts of earthquakes on health can be
divided into immediate, intermediate, and long-term effects. Power outages and
fuel crises have health hazards at all stages. It is imperative to understand the
temporal effects of earthquakes, because the major needs soon after the
earthquake (emergency care) are vastly different from long-term needs such as
rehabilitation and psychosocial support. In Nepal, the inadequate and nearly
nonexistent specialized health care at the peripheral level claimed many lives
during the earthquakes and left many people disproportionately injured.
Preemptive strategies such as mobile critical care units at primary health
centers, intensive care training for health workers, and alternative plans for
emergency care must be prioritized. Similarly, infrastructural damage led to poor
sanitation, and alternative plans for temporary settlements (water supply, food,
settlements logistics, space for temporary settlements) must be in place where
the danger of disease outbreak is imminent. While much of these strategies are
implementable and are often set as priorities, long-term effects of earthquakes
such as physical and psychosocial supports are often overlooked. The burden of
psychosocial stresses, including depression and physical disabilities, needs to
be prioritized by facilitating human resources for mental health care and
rehabilitation. In addition, inclusion of mental health and rehabilitation
facilities in government health care services of Nepal needs to be prioritized.
Similarly, power outages and fuel crises affect health care disproportionately.
In the current context where permanent solutions may not be possible, mitigating
health hazards, especially cold chain maintenance for essential medicines and
continuation of life-saving procedures, are mandatory and policies to regulate
all health care services must be undertaken. (Disaster Med Public Health
Preparedness. 2017;11:625-632).
PMID- 28416044
TI - Treatment of PTSD-Related OSA With CPAP is Associated With Only a Modest
Improvement in PTSD: Possible Adjunctive Treatment With Mood Stabilizers.
PMID- 28416043
TI - Delaying Middle School and High School Start Times Promotes Student Health and
Performance: An American Academy of Sleep Medicine Position Statement.
AB - ABSTRACT: During adolescence, internal circadian rhythms and biological sleep
drive change to result in later sleep and wake times. As a result of these
changes, early middle school and high school start times curtail sleep, hamper a
student's preparedness to learn, negatively impact physical and mental health,
and impair driving safety. Furthermore, a growing body of evidence shows that
delaying school start times positively impacts student achievement, health, and
safety. Public awareness of the hazards of early school start times and the
benefits of later start times are largely unappreciated. As a result, the
American Academy of Sleep Medicine is calling on communities, school boards, and
educational institutions to implement start times of 8:30 AM or later for middle
schools and high schools to ensure that every student arrives at school healthy,
awake, alert, and ready to learn.
PMID- 28416045
TI - Hypnotics and the Risks of Dementia.
PMID- 28416046
TI - Challenges in the Management of Sleep Apnea and PTSD: Is the Low Arousal
Threshold an Unrealized Target?
PMID- 28416047
TI - Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential
Promulgator of Atrial Fibrillation in Ischemic Stroke.
PMID- 28416048
TI - AASM Scoring Manual Updates for 2017 (Version 2.4).
PMID- 28416049
TI - A Restless Farewell in Changing Times: Advice for the Field of Sleep Medicine.
PMID- 28416050
TI - Proteomic analysis of the endometrium during early pregnancy in the domestic pig.
AB - Reproductive processes in domestic pigs have been studied extensively. Pigs are
one of the main sources of meat for human consumption and are an established
model for investigations into mammalian, including human, reproductive
physiology. Studies of the uterus during early pregnancy will lead to a better
understanding of mechanisms governing pregnancy. Proteomics provides the
possibility to explore endometrial functions in an unbiased way. The aim of the
study was to compare endometrium harvested from Days 12-13 and 15-16 of pregnancy
with the corresponding days of the oestrous cycle. We identified endometrial
proteins that are unique to the early stages of pregnancy (Days 12-13 and 15-16).
Twenty-one proteins were identified that were uniquely expressed on the selected
days of pregnancy or the oestrous cycle. Out of 21 identified proteins, 14
referred to the pregnancy periods. Systemic analysis of the identified proteins
revealed cell adhesion and cytoskeletal organisation as two of the major
functions, both of which are important for the establishment and maintenance of
pregnancy. Thrombospondin 1 expression was validated using western blotting
analysis and the results suggest its involvement in the adhesiveness of the
embryo during the peri-implantation period in pigs.
PMID- 28416051
TI - [Mirror syndrome is a rare complication in pregnancy, characterized by oedema and
hydrops fetalis].
AB - We describe a case of mirror syndrome. A 41-year-old woman, para 4, was referred
to hospital at 32 weeks of gestational age with excessive oedema. She developed
oliguria, mild hypertension and proteinuria. Fetal ultrasound confirmed severe
hydrops fetalis. Intrauterine pleural drainage was performed without improvement
of the condition. Since maternal symptoms worsened, a caesarean section was
performed at 34 weeks with delivery of a live hydropic girl who died after 17
hours. Maternal symptoms decreased four days after delivery with full recovery
two weeks post-partum.
PMID- 28416052
TI - [A 38-year-old woman with an anovaginal fistula after consensual penile anal
intercourse].
AB - In this case report a 38-year-old woman was admitted to hospital with anal
bleeding and perianal pain after a consensual vaginal intercourse followed by an
anal intercourse during which she felt a sudden profound pain. Nine days later
she was diagnosed with an anovaginal fistula. A diverting sigmoideostomy was
performed, and spontaneous healing was awaited. Rectovaginal fistula without
concomitant anal sphincter injury as a result of consensual penile anal
intercourse is an extremely rare occurrence, described only once previously.
PMID- 28416053
TI - [Treatment of anaphylactic schock in pregnant women].
AB - This is an update on the treatment of anaphylactic shock in pregnant women. Most
guidelines recommend adrenaline as first-line treatment in all patients, but in
pregnant patients some recommend ephedrine due to a potential risk of utero
placental hypoperfusion with adrenaline. However, ephedrine is a less potent
vasopressor than adrenaline and does not possess the same anti-inflammatory or
broncho-dilating effects. As immediate and correct treatment is essential for
both the maternal and the fetal outcome, adrenaline should be first-line
treatment also in pregnant women.
PMID- 28416054
TI - [Combined endoscopic laparoscopic colon polypectomy].
AB - Combined endoscopic laparoscopic surgery (CELS) is a novel technique for
resection of benign colon polyps, which are not amenable for endoscopic
resection. A review of ten studies including 416 patients shows that polyps were
successfully resected in 65-97% of the patients. Polyp recurrence after CELS is
low, and the frequency of adenocarcinoma is comparable with the frequency in
large polyps (> 2 cm) resected endoscopically. CELS can be performed for a
variety of indications but should be done after renewed endoscopy. Due to the
risk of cancer it should only be performed in specialized centres.
PMID- 28416055
TI - [Akut infantilt haemoragisk odem].
PMID- 28416056
TI - ?
PMID- 28416057
TI - ?
PMID- 28416058
TI - ?
PMID- 28416059
TI - [Amelanotisk malignt melanom pa en finger].
PMID- 28416060
TI - [Gas-filled liver metastases caused by Clostridium septicum sepsis].
AB - In this case report a 73-year-old male with liver-metastatic colon cancer was
admitted to hospital due to severe abdominal pain merely four days after
receiving chemotherapy including epidermal growth factor receptor inhibitors. An
acute computed tomography revealed gas-filled liver metastases with two possible
diagnoses of either a rapid tumour response resulting in tumour necrosis or
severe bacterial infection involving liver metastases. Moreover, the patient had
an anaerobic infection with Clostridium septicum, and despite relevant treatment
he died within 12 hours after admission.
PMID- 28416061
TI - [Bouveret's syndrome - a rare complication in connection with cholecystolithiasis
and a variant of gallstone ileus].
AB - Bouveret's syndrome is a very rare complication to cholecystolithiasis resulting
in gallstone ileus. It is caused by ectopic gallstones in the duodenum due to a
bilioenteric fistula. Symptoms may include vomiting and upper abdominal pains.
The condition is associated with high mortality, making it important to
recognize. The treatment includes surgical removal of the gallstone. However, the
optimal therapeutic approach has still not been found. In this case report a 59
year-old female with Bouveret's syndrome is presented.
PMID- 28416062
TI - [Growing pains are well-known, but the cause remains unclear].
AB - A common complaint from children is growing pains: a mild to severe pain located
primarily in the legs and being most intense in evenings and during sleep. The
diagnosis is based on the characteristics of the pain and careful clinical
examination. The pain disappears as the child grows up. Research has suggested
that the pain occurs more often in children who suffer from vitamin D deficiency,
low bone density, low pain threshold, restless legs syndrome and in children who
were breastfed for less than 40 days from birth. There are not yet any firm
conclusions about the aetiology.
PMID- 28416063
TI - [Repetitive transcranial magnetic stimulation treatment for post-traumatic stress
disorder].
AB - Approximately 10% of combat soldiers and 30% of rape victims develop post
traumatic stress disorder (PTSD). Repetitive transcranial magnetic stimulation
(rTMS) is already known to be safe in depression treatment. Research results of
the past 15 years indicate that rTMS induced to the right dorsolateral prefrontal
cortex may have a potential to treat the symptoms of PTSD. Furthermore, high
frequency rTMS seems to be superior to low-frequency rTMS. The effect of rTMS on
PTSD symptoms could be mediated by increasing the level of brain-derived
neurotrophic factor.
PMID- 28416065
TI - ?
PMID- 28416064
TI - [Evaluation and treatment of patients after caustic ingestion].
AB - This article presents recommendations regarding early management of patients
after intake of corrosive chemicals, based on best evidence and clinical
experience. Risk assessment built on clinical history, presentation and endoscopy
is discussed as well as initial treatment, surgical appraisal and observation.
Controversy still surrounds the need for endoscopy in asymptomatic patients, the
use of computed tomography in assessing the severity of lesions as well as
pharmacological treatment for preventing strictures.
PMID- 28416066
TI - ?
PMID- 28416067
TI - ?
PMID- 28416068
TI - [Treatment with low-dose acetylsalicylic acid can reduce risk of pre-eclampsia in
high-risk pregnant women].
AB - Pre-eclampsia is a major contributor to perinatal morbidity and mortality. Large
studies of high-risk pregnant women have shown reduced risk of developing pre
eclampsia when they are treated with low-dose acetylsalicylic acid in early
pregnancy. Treatment is also effective in preventing intrauterine growth
restriction, preterm birth and perinatal death. No major side effects, including
risk of malformations or miscarriage, are reported. It is important that general
practitioners are aware of women who have an increased risk of developing pre
eclampsia, so that treatment with 100 mg of acetylsalicylic acid can be started
early in pregnancy.
PMID- 28416069
TI - [Dietary treatment of medically refractory epilepsy in children and adolescents].
AB - Ketogenic diet (KD) is used worldwide in the treatment of medically refractory
epilepsy. Since the introduction of KD in the early 1900s, new approaches such as
medium-chain triglyceride ketogenic diet, modified Atkins diet and low glycaemic
index treatment have been suggested as alternative treatments. Several studies
have documented significant seizure reduction from all four diets. The aim of
this article is to give an overview of the effect of dietary treatment and to
discuss advantages in initiating dietary treatment as an early treatment instead
of as a last option.
PMID- 28416070
TI - [Intentional suicide with cyclizine].
AB - Cyclizine is an antihistamine with a sedative effect. In Denmark it is an over
the-counter drug, whereas it is a prescription drug in many other countries. It
possesses anticholinergic and antiemetic properties, although the exact mechanism
of action is unknown. At doses greater than 5 mg/kg potent side effects of
anticholinergic character can be expected. This case report is a description of
an intentional suicide with a dose greater than 70 mg/kg.
PMID- 28416071
TI - [Acute upper airway obstruction caused by a multinodular goitre after
tracheotomy].
AB - This case report illustrates how a multinodular goitre caused acute airway
obstruction in a multitrauma 66-year-old male after tracheotomy. The patient had
no symptoms of the goitre before the tracheotomy but developed subglottic airway
obstruction at the time of decannulation. He underwent a subacute total
thyroidectomy which removed the obstructive symptoms. A weakening of the tracheal
tube followed by the tracheotomy possibly caused the tracheal stenosis in
combination with the goitre.
PMID- 28416072
TI - [A Scandinavian guideline for initial management of minimal, mild and moderate
head trauma in children].
AB - The Scandinavian Neurotrauma Committee has recently published an evidence- and
consensus-based guideline for the management of minor and moderate head trauma in
children. They aim is to select children for computed tomography (CT) scan,
observation or early discharge, with the attempt to reduce the number of CT scans
in children without missing any significant intracranial injury in need for
treatment. A flow chart of the guidelines and a help sheet has been developed for
clinical use. Suggestions for in-hospital observation and parental information
are also presented. We present the guideline in Danish.
PMID- 28416073
TI - [The implications of using different body mass index references in children and
adolescents].
AB - To classify children as overweight or obese, their body mass index (BMI) must be
compared with a growth reference and be accompanied by a clinical assessment. In
Denmark, there is a lack of consensus on which BMI reference to use; a mix of
national and international references are used in clinics, hospitals and research
institutions. In this article, the implications of using different references are
illustrated with Danish data. The comparisons show that the references yield
different prevalences of overweight in a non-predictable way, making comparisons
and monitoring challenging.
PMID- 28416074
TI - [The stratified H-index makes scientific impact transparent].
AB - The H-index is widely used to quantify and standardize researchers' scientific
impact. However, the H-index does not account for the fact that co-authors rarely
contribute equally to a paper. Accordingly, we propose the use of a stratified H
index to measure scientific impact. The stratified H-index supplements the
conventional H-index with three separate H-indices: one for first authorships,
one for second authorships and one for last authorships. The stratified H-index
takes scientific output, quality and individual author contribution into account.
PMID- 28416075
TI - Muscle strength rather than muscle mass is associated with osteoporosis in older
Chinese adults.
AB - BACKGROUND: Assessment of the association of muscle strength and muscle mass with
osteoporosis (OP) is of special interest as muscles are a potential target for
interventions (i.e., strength training). METHODS: A cross-sectional descriptive
study encompassing people aged >= 60 years (average age: 66.9 +/- 6.2 years; men,
n = 516; women, n = 652) in the Hangu area of Tianjin, China. The study
populations were invited to participate in a comprehensive geriatric assessment.
OS was identified by measuring the calcaneal using a quantitative ultrasound and
a T score of less than -2.5. Muscle characteristics included grip strength and
appendicular skeletal muscle mass (ASM). RESULTS: The prevalence of OS in this
study was 61.6% (male 52.1%, female 69.1%). Grip strength was negatively related
to OS and after adjusting for all other variables, higher grip strength was found
to be associated with a lower OS risk (p = 0.023). ASM/height2 was not associated
with OS (p = 0.205). CONCLUSION: Based on our study, muscle strength rather than
muscle mass is negatively associated with OS in older people; thus, we should pay
more attention to muscle strength training in the early stage of the OS.
PMID- 28416076
TI - Sweat allergy: Extrinsic or intrinsic?
AB - Sweat is an exacerbation factor in atopic dermatitis (AD) in all age groups. A
body core temperature elevation with sweating triggers cholinergic urticaria
(CholU). We recently reported that AD symptoms are improved by tannic acid
containing spray, which suppresses the basophil histamine release induced by semi
purified sweat antigen in vitro, and by showering, which removes antigens in
sweat from the skin surface. Sweat contains small amount of proteins including
proteases, protease inhibitors, and anti-microbial peptides. We finally
identified MGL_1304 secreted by Malassezia (M.) globosa as a major histamine -
releasing antigen in human sweat. MGL_1304 is a 17-kDa protein in sweat that
elicits almost the highest histamine - release activity from basophils of
patients with AD and CholU among antigens derived from Malassezia species.
Moreover, serum levels of anti-MGL_1304 IgE were significantly higher in patients
with AD and CholU than in normal controls. The recombinant protein produced by
Pichia pastoris possessed comparable allergenicity to native MGL_1304. We found a
monoclonal IgE antibody against MGL_1304 which did not elicit histamine release
from sensitized mast cells. Desensitization therapy using autologous sweat, or
MGL_1304 purified from culture of M. globosa or its cognates might be beneficial
for patients with intractable CholU due to sweat allergy.
PMID- 28416078
TI - Corrigendum to "Caring for children with intellectual disabilities part 1:
Experience with the population, pain-related beliefs, and care decisions" [Res.
Dev. Disabil. 62 (2017) 197-208].
PMID- 28416077
TI - Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent
Suppression of Caveolae-Mediated Transcytosis.
AB - The blood-brain barrier (BBB) provides a constant homeostatic brain environment
that is essential for proper neural function. An unusually low rate of vesicular
transport (transcytosis) has been identified as one of the two unique properties
of CNS endothelial cells, relative to peripheral endothelial cells, that maintain
the restrictive quality of the BBB. However, it is not known how this low rate of
transcytosis is achieved. Here we provide a mechanism whereby the regulation of
CNS endothelial cell lipid composition specifically inhibits the caveolae
mediated transcytotic route readily used in the periphery. An unbiased lipidomic
analysis reveals significant differences in endothelial cell lipid signatures
from the CNS and periphery, which underlie a suppression of caveolae vesicle
formation and trafficking in brain endothelial cells. Furthermore, lipids
transported by Mfsd2a establish a unique lipid environment that inhibits caveolae
vesicle formation in CNS endothelial cells to suppress transcytosis and ensure
BBB integrity.
PMID- 28416080
TI - Molecular identification and immunological characteristics of goose suppressor of
cytokine signaling 1 (SOCS-1) in vitro and vivo following DTMUV challenge.
AB - Purpose suppressor of cytokine signaling 1 (SOCS-1) is inducible feedback
inhibitors of cytokine signaling and involved in viral infection through
regulation of both innate and adaptive immunity. In this study, we firstly cloned
SOCS-1 (goSOCS-1) from duck Tembusu virus (DTMUV) infected goose. The full-length
sequence of goSOCS-1 ORF is 624bp and encoded 108 amino acids. Structurally, the
mainly functional regions (KIR, SH2, SOCS-box) were conserved between avian and
mammalian. The tissues distribution data showed SOCS-1 highly expressed in immune
related tissues (SP, LU, HG) of both gosling and adult goose. Moreover, the
goSOCS-1 transcripts were induced by goIFNs in GEFs and by TLR ligands in PBMCs.
Notably, upon DTMUV infection, highly expression level of goSOCS-1 was detected
in vitro and in vivo with high viral load. Our results indicated that goSOCS-1
might involve in both innate and adaptive antiviral immunity of waterfowl.
PMID- 28416079
TI - Management of Childhood Congenital Adrenal Hyperplasia-An Integrative Review of
the Literature.
AB - Congenital adrenal hyperplasia (CAH) is an endocrine condition that requires
parents to administer steroids up to three times daily, supplementing maintenance
doses with oral or injectable doses during times of illness. The purpose of this
integrative review was to explore the management, care, and associated health
issues for children with CAH and the family response to the condition. Four
literature indexes were searched, with 39 articles included. Four themes emerged:
(a) Health- and Development-Related Issues, (a) Effects of Excess Androgens, (c)
Life Experience of CAH, and (d) Managing and Averting Adrenal Crisis. Families
having a child with CAH face complex concerns related their child's growth, the
fear of adrenal crisis events, and the consequences of atypical genitalia for
affected girls. Future studies should focus on interventions that provide
guidelines to increase parental preparedness in managing adrenal crises and
creating support systems for affected girls.
PMID- 28416081
TI - Reversible cerebral vasoconstriction syndrome combined with posterior reversible
encephalopathy syndrome after heart transplantation.
AB - Reversible cerebral vasoconstriction syndrome (RCVS) combined with posterior
reversible encephalopathy syndrome (PRES) is a rare complication in patients
treated with immunosuppressants. A 52-year-old male patient presented with
seizures after heart transplantation. The patient was suspected of having PRES on
brain images. Despite the strict blood pressure control, the patient presented
with altered mentality and the brain images showed a newly developed large acute
infarction. Digital subtraction angiography (DSA) revealed the classic "sausage
on a string" appearance of the cerebral arteries - potential feature of RCVS. To
our knowledge, this is the first case report to describe RCVS combined with PRES
after heart transplantation.
PMID- 28416082
TI - Final diagnosis of patients with clinically suspected vestibular neuritis showing
normal caloric response.
AB - Vestibular neuritis is one of the most common peripheral causes of acute
vestibular syndrome, of which the diagnosis is generally based on a comprehensive
interpretation of clinical and laboratory findings following reasonable exclusion
of other disorders. This study aimed to investigate the final diagnosis of
patients admitted to hospital under the clinical impression of vestibular
neuritis who showed no unilateral caloric paresis. Forty-five patients who
visited the emergency department with isolated acute spontaneous vertigo were
included. Among them, six patients (13%) developed definitive spontaneous vertigo
lasting longer than 20min again after discharge from hospital, accompanied by
hearing loss, which was audiometrically documented, leading to a final diagnosis
of definite Meniere's disease. Nine patients (20%) revisited our clinic with
recurrent episodic vertigo without any documented hearing loss or auditory
symptoms such as hearing loss, tinnitus or ear fullness, which led to a final
diagnosis of possible Meniere's disease. In four patients (9%), initial
spontaneous vertigo and nystagmus changed to positional vertigo and nystagmus on
the second hospital day. In 26 patients (58%), neither another episode of vertigo
nor auditory symptoms developed during follow-up period (7-92months), a condition
to which the authors gave an arbitrary diagnosis of "mild unilateral vestibular
deficit". In conclusion, patients admitted to hospital under clinical impression
of vestibular neuritis may have various final diagnoses, and "mild unilateral
vestibular deficit" was the most common final diagnosis among patients who did
not meet the diagnostic criteria of vestibular neuritis.
PMID- 28416083
TI - Prevalence and Occupation of Patients Presenting With Dysphonia in the United
States.
AB - OBJECTIVE: Voice disorders are common conditions that may have a significant
impact on patient quality of life, yet their prevalence and epidemiology are
poorly documented. In this study, we estimated the prevalence, demographics, and
occupation of patients with dysphonia. METHODS: Using the Commercial and Medicare
MarketScan databases of 146.7 million lives (2008-2012), the prevalence of
dysphonia was estimated. Patient demographics and industry occupation were
evaluated. Prevalence estimates overall and by industry were made using Medical
Expenditure Panel Survey. Industry estimates were compared with US government
employment statistics to assess differences between dysphonia and the general
population. RESULTS: A gradual increase in the diagnosis of dysphonia was noted
from 1.3% to 1.7% of the population from 2008 to 2012, with an associated
increase in the diagnosis of acute laryngitis, the largest diagnostic category. A
strong correlation was present between diagnosis and age, with acute laryngitis
more common in the younger populations and malignancies in older ages. Benign
neoplasms were more prevalent in the service industry, with 2.6 times increased
likelihood compared with the general population, and malignancies were more
prevalent in the manufacturing industry, with 1.4 times increased likelihood.
Almost 3 million laryngoscopies and stroboscopies were performed with $900
million in costs. CONCLUSION: Prevalence rates of the diagnosis of dysphonia are
increasing and are associated with large healthcare costs. Prevalence rates also
differ somewhat between industries, and there appears to be a higher percentage
of malignant neoplasms in the manufacturing industry and benign neoplasms in the
service industry.
PMID- 28416084
TI - A conceptual framework for negotiating public involvement in municipal waste
management decision-making in the UK.
AB - The technical expertise that politicians relied on in the past to produce cost
effective and environmentally sound solutions no longer provides sufficient
justification to approve waste facilities. Local authorities need to find more
effective ways to involve stakeholders and communities in decision-making since
public acceptance of municipal waste facilities is integral to delivering
effective waste strategies. This paper presents findings from a research project
that explored attitudes towards greater levels of public involvement in UK waste
management decision-making. The study addressed questions of perception,
interests, the decision context, the means of engagement and the necessary
resources and capacity for adopting a participatory decision process. Adopting a
mixed methods approach, the research produced an empirical framework for
negotiating the mode and level of public involvement in waste management decision
making. The framework captures and builds on theories of public involvement and
the experiences of practitioners, and offers guidance for integrating analysis
and deliberation with public groups in different waste management decision
contexts. Principles in the framework operate on the premise that the decision
about 'more' and 'better' forms of public involvement can be negotiated, based on
the nature of the waste problem and wider social context of decision-making. The
collection of opinions from the wide range of stakeholders involved in the study
has produced new insights for the design of public engagement processes that are
context-dependent and 'fit-for-purpose'; these suggest a need for greater
inclusivity in the case of contentious technologies and high levels of
uncertainty regarding decision outcomes.
PMID- 28416085
TI - Delamination mechanism study of large size waste printed circuit boards by using
dimethylacetamide.
AB - Present work investigates the recycling of waste printed circuit boards (PCBs) by
cracking of its multi-layered structure by using dimethylacetamide (DMA). The
study shows that cracking and separation of layers of PCBs increases as the
temperature increases; and decreases as the surface area of PCBs increases. After
separation of layers, the used solvent was analyzed by proton and carbon nuclear
magnetic resonance spectroscopy (NMR) to understand the dissolution phenomenon of
resin. Further, NMR and Fourier transform infrared spectroscopy analysis of DMA
sample after 1h, 2h, 3h, 4h and 8h of reaction with PCBs at 433K and PCB:DMA
ratio (wt/vol) of 3:10 has been carried out to investigate the mechanism of
dissolution of resin. These studies revealed that hydroxyl group of PCBs
polymeric chain participates in hydrogen bonding with parent carbonyl group of
DMA molecule that results in the solvation of resin. Possible chemical reaction
based on the above finding has been discussed. Using this technique, separation
of the metallic fraction without application of any energy intensive mechanical
pre-processing is possible.
PMID- 28416086
TI - History of Depression in Lung Cancer Patients: Impact of Delay.
AB - AIMS: To examine the influence of a history of depression in the process of
diagnostic evaluation and the choice of treatment in lung cancer. MATERIALS AND
METHODS: The analysis was based on all patients with non-small cell lung cancer
who were registered in 2008-2014; in total, 27 234 patients. To estimate the
effect of depression on the diagnostic process and the choice of treatment in
lung cancer we fitted a logistic regression model and a Cox regression model
adjusting for age, gender, resection and stage. RESULTS: Depression in a
patient's anamnesis had no significant effect on the delay in diagnostic
evaluation (hazard ratio = 0.99 with 95% confidence interval 0.90; 1.09).
Patients with a history of periodic depression had a 33% lower treatment rate
(odds ratio = 0.66 with 95% confidence interval 0.51; 0.85) than patients without
a history of depression. CONCLUSIONS: Our study shows that patients with a
history of periodic depression need special attention when diagnosed with lung
cancer.
PMID- 28416087
TI - The impact of joint angle and movement velocity on sex differences in the
functional hamstring/quadriceps ratio.
AB - BACKGROUND: Females are two to eight times more likely to suffer a non-contact
injury compared with males thus the purpose of this study was to explore the
influence of joint angle and movement velocity on sex differences in the
functional hamstring to quadriceps ratio (H/QFUNC). METHODS: Isokinetic
concentric and eccentric torque were determined in 110 participants (55 males and
55 females) through a 90 degrees range of movement at 60, 120, and 240 degrees
/s. Testing was performed with the hip flexed at 10 degrees . The H/QFUNC was
determined at three specific joint angles (15, 30 and 45 degrees flexion) and
where peak torque occurred for concentric knee extension. RESULTS: A significant
interaction effect (P<0.01) for sex and joint angle was observed with women
demonstrating a lower H/QFUNC than males, especially at more extended knee
positions. A significant sex by velocity interaction (P<0.01) indicated a lower
H/QFUNC in women as velocity increased. Significant main effects (P<0.01)
indicated that irrespective of sex the H/QFUNC increased as the knee extends and
velocity increases. CONCLUSION: Given the reduced H/QFUNC in females compared to
males at more extended knee positions and faster velocities, this may contribute
to the observed sex bias in reported injury rates.
PMID- 28416089
TI - Recurrent Stroke and Early Mortality in an Urban Medical Unit in Cameroon.
AB - BACKGROUND: Data on stroke mortality in recurrent strokes in the context of
limited acute stroke care and secondary stroke prevention within Africa are very
scant. We investigated the risk of in-hospital death in patients with recurrent
stroke in the medical department of the Yaounde Central Hospital in Cameroon.
METHODS: Admission and discharge registries, and patient files for the period
1999-2012, were reviewed for evidence of admission for stroke, recurrent stroke,
and in-hospital death. Mortality was compared between recurrent and first-ever
stroke overall, and heterogeneities across major subgroups were assessed via
interaction tests. RESULTS: Out of 1678 participants included in the final
analytic sample, 243 (14.5%) had recurrent stroke. Our first-ever stroke
participants were older (median age 65.0 years versus 62.0 years, P = .024), had
a worse stroke risk profile (prevalent diabetes 17.5% versus 12.0%, P = .018;
atrial fibrillation 3.7% versus 1.1%, P = .002; hypertension 91.7% versus 63.9%,
P < .0001), and were smokers. Sixty-five deaths (20.6%) occurred among
participants with recurrent stroke and 281 (19.6%) among first-ever stroke
participants (P = .013). The adjusted odds ratio of mortality from recurrent
stroke was 1.43 (95% CI: 1.03-1.99). CONCLUSION: Stroke survivors have a 43%
higher risk of dying after a recurrent stroke compared to those with first-ever
stroke, against a background of unfavorable stroke risk profile.
PMID- 28416088
TI - A novel MIS technique for posterior cruciate ligament avulsion fractures.
AB - OBJECTIVE: Open surgical approaches to treat tibial avulsion fractures of the
posterior cruciate ligament (PCL) often use large incisions involving extensive
muscle dissection and retraction. The objective of this study was to describe a
new mini-invasive approach targeting the fractured zone, to minimize surgical
dissection and improve recovery and rehabilitation. METHODS: The new approach was
used in 15 males and seven females with isolated PCL avulsions. The length of the
surgical incision, surgical time, need for conversion to open technique, visual
analog scores (VAS) and duration of hospital stay were studied to assess the
efficacy, learning curve and advantages of the new technique. Neurovascular
complications were recorded. At the two-year follow-up, International Knee
Documentation Committee (IKDC) scores were recorded to assess function. RESULTS:
Patients were followed up for a mean of 29months (range: 34-41). The mean length
of the incision was 4.1cm (range: 3.4 to five) measured at the end of the
procedure. None of the patients required conversion to an open technique and no
neurovascular complications were recorded. The mean surgical time was 40min
(range: 25-50). The mean VAS on discharge was 2.2 (range: one to four) and
patients stayed at the hospital for a mean of 2.2days (range: one to three). The
mean IKDC score at one-year post surgery was 86.4 (range: 83.9-90.8).
CONCLUSIONS: The new mini-invasive targeted approach provides adequate exposure
for performing internal fixation of PCL avulsion fractures without the surgical
morbidity associated with conventional open surgical approaches. The procedure is
safe, fast and does not require a long learning curve.
PMID- 28416090
TI - Clipping in Awake Surgery as End-Stage in a Complex Internal Carotid Artery
Aneurysm After Failure of Multimodal Endovascular and Extracranial-Intracranial
Bypass Treatment.
AB - BACKGROUND: Intracranial carotid artery aneurysm can be treated via microsurgical
or endovascular techniques. The optimal planning is the result of the careful
patient selection through clinical, anatomic, and angiographic analysis. CLINICAL
PRESENTATION: We present a case of ruptured internal carotid artery (ICA)
aneurysm that became a complex aneurysm after failure of multi-endovascular and
surgery treatment. We describe complete trapping in awake craniotomy after
failure of coiling, stenting, and bypassing. CONCLUSIONS: ICA aneurysms could
become complex aneurysms following multi-treatment failure. Endovascular
approaches to treat ICA aneurysms include coiling, stenting, flow diverter
stenting, and stenting-assisted coiling technique. The role of surgery remains
relevant. To avoid severe neurologic deficits, recurrence, and the need of
retreatment, a multidisciplinary discussion with experienced endovascular and
vascular neurosurgeons is mandatory in such complex cases.
PMID- 28416091
TI - Corrigendum to "Glucose enhances tilapia against Edwardsiella tarda infection
through metabolome reprogramming" [Fish and Shellfish Immunol. 61 (2017) 34-43].
PMID- 28416092
TI - Cytokines and C-reactive protein alterations with respect to cognitive impairment
in schizophrenia and bipolar disorder: A systematic review.
AB - BACKGROUND: The aim of this article was to perform a systematic review of studies
investigating the association between peripheral levels of cytokines and C
reactive protein (CRP), cytokine gene polymorphisms and cognition in patients
with schizophrenia and bipolar disorder (BD). METHODS: The following databases:
PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source:
Nursing/Academic Edition databases were searched according to the PRISMA
guidelines. We included studies that investigated the association between
peripheral levels of CRP and cytokines, cytokine gene polymorphisms and cognitive
performance in schizophrenia and/or BD patients. Subsequently, quality assessment
of eligible publications was performed. Results were synthesized by discussing
main findings around correlations between inflammatory markers and cognition.
RESULTS: Most consistent results indicate worse cognitive performance in
schizophrenia patients with higher CRP levels. Less consistent evidence suggests
better cognitive functioning of schizophrenia patients with higher levels of
tumour necrosis factor-alpha (TNF-alpha). Evidence for the involvement of other
cytokines in cognitive impairment in patients with schizophrenia is less
convincing due to discordant results or scarcity of studies. Due to low number of
studies, it is difficult to draw conclusions on the involvement of CRP and
cytokine alterations in the development of cognitive deficits in BD. Single
studies suggest the role of CRP, interleukin(IL)-1 receptor antagonist, IL-6 and
TNF-alpha with its receptors in the development of cognitive impairment in BD.
CONCLUSIONS: Peripheral inflammation might be related to cognitive deficits in
schizophrenia and BD. Unequivocal conclusions cannot be made due to
methodological heterogeneity and low number of studies investigating particular
cytokines.
PMID- 28416093
TI - The role of cognitive functioning in the relationship between childhood trauma
and a mixed phenotype of affective-anxious-psychotic symptoms in psychotic
disorders.
AB - Cognitive impairments in patients with psychotic disorder have been associated
with poor functioning and increased symptom severity. Furthermore, childhood
trauma (CT) exposure has been associated with worse cognitive functioning as well
as co-occurrence of affective-anxious-psychosis symptoms or a 'mixed phenotype of
psychopathology' (MP), which in turn is associated with greater symptom severity,
and poor functioning. This study aims to evaluate if cognition could be
associated with CT/MP. 532 patients with non-affective psychotic patients were
assessed on CT, symptom profile, cognition, functioning, and symptom severity at
baseline and 3 and 6-year follow-up. Four subgroups were made according to trauma
exposure (CT- or CT+) and presence of a mixed phenotype (MP- or MP+): CT-/MP
(n=272), CT-/MP+ (n=157), CT+/MP- (n=49), and CT+/MP+ (n=54). Mixed-effects
multilevel regression, linear regression, and Tobit analyses were performed.
Patients with both CT and MP showed lower verbal learning and memory than CT-/MP+
individuals (p<0.001). No other significant differences were found among the 4
subgroups. No cognitive decline was found at follow-up, neither in the CT+/MP-
nor in CT-/MP- group. Lower cognition was not associated with increased symptom
severity or poor functioning at follow-up, neither in the CT+/MP- nor in CT-/MP-
group. Although cognitive impairments and CT may be related to clinical or
functional features of psychotic disorder, and cognitive functioning could be
affected by CT exposure, cognition does not discriminate subgroups of patients
stratified by CT exposure and MP.
PMID- 28416094
TI - The effect of tDCS on auditory hallucination and P50 sensory gating in patients
with schizophrenia: A pilot study.
PMID- 28416095
TI - Self- and other-agency in people with passivity (first rank) symptoms in
schizophrenia.
AB - Individuals with passivity (first-rank) symptoms report that their actions,
thoughts and sensations are influenced or controlled by an external (non-self)
agent. Passivity symptoms are closely linked to schizophrenia and related
disorders yet they remain poorly understood. One dominant framework posits a role
for deficits in the sense of agency. An important question is whether deficits in
self-agency can be differentiated from other-agency in schizophrenia and
passivity symptoms. This study aimed to evaluate self- and other-agency in 51
people with schizophrenia (n=20 current, 10 past, 21 no history of passivity
symptoms), and 48 healthy controls. Participants completed the projected hand
illusion (PHI) with active and passive movements, as well as immediate and
delayed visual feedback. Experiences of agency and loss of agency over the
participant's hand and the image ('the other hand') were assessed with a self
report questionnaire. Those with passivity symptoms (current and past) reported
less difference in agency between active and passive movements on items assessing
agency over their own hand (but not agency over the other hand). Relative to the
healthy controls, the current and never groups continued to experience the
illusion with delayed visual feedback suggesting impaired timing mechanisms
regardless of symptom profile. These findings are consistent with a reduced
contribution of proprioceptive predictive cues to agency judgements specific to
self representations in people with passivity symptoms, and a subsequent reliance
on external visual cues in these judgements. Altogether, these findings emphasise
the multifactorial nature of agency and the contribution of multiple impairments
to passivity symptoms.
PMID- 28416096
TI - Treatment outcomes of archwise distraction osteogenesis in mandibular
dentoalveolar retrognathia cases.
AB - The aim of this study was to describe the treatment of class II malocclusion by
sagittal advancement of the alveolar bone in the symphyseal area using an
intraoral archwise distractor device and to determine the effects of this method
on the dentoalveolar complex. Fifteen patients (10 female, five male) aged 16-20
years with a class II division 2 malocclusion, characterized by mandibular
dentoalveolar retrusion and a prominent chin, underwent archwise alveolar
distraction in the anterior mandible. Lateral cephalometric radiographs were
obtained before distraction (T0), after 6 weeks of consolidation (T1), and after
debonding (T2). Linear and angular skeletal, dental, and soft tissue measurements
were performed. Forty-seven parameters were measured for each of the 15 subjects
on pre- and postoperative lateral cephalometric radiographs (T0, T1, and T2). The
distraction protocol was successful in all patients. Skeletally, the mandible
showed a clockwise rotation. B-point moved forward significantly (P<0.05).
Overjet decreased significantly (P<0.001). The total profile angle was
unaffected, and the improvement in the submental fold was highly significant
(P<0.001). The intraoral archwise distraction force that is applied through
brackets and archwires is sufficiently effective for alveolar advancement. This
procedure is simple and effective in the treatment of specific adult patients
with a class II division 2 malocclusion, characterized by a prominent chin and
severe mandibular dentoalveolar retrusion.
PMID- 28416097
TI - Long-term effect of presurgical nasoalveolar molding on growth of maxillary arch
in unilateral cleft lip and palate: randomized controlled trial.
AB - The objective of this study was to investigate the long-term effect of
presurgical nasoalveolar molding (PNAM) on growth of the maxillary arch through
early childhood until 6 years of age in complete unilateral cleft lip and palate
(UCLP) patients presenting for PNAM at different ages. Complete UCLP patients who
were treated at our centre were divided into two groups. The study group
underwent PNAM and was further subdivided into three subgroups (PNAM initiated
within 1 month, between 1 and 6 months, and between 6 and 12 months of age in
subgroup I, II, and III, respectively). The control group did not undergo PNAM
and was further subdivided into three subgroups. Patients were evaluated at T1
(first visit), T2 (before cheiloplasty), and T3 (at 6 years). Between T1and T2,
the intersegment distance (ISD) reduced significantly in the study group but
increased in the control group, whereas the intercanine width (ICW) in both the
study and control groups did not show significant change. Between T2 and T3, ISD
and ICW were reduced significantly in the control group due to arch collapse,
whereas in the study group, ISD reduced slightly with ICW remaining almost
similar to noncleft norms. We conclude that reduced ISD following PNAM improves
arch symmetry and stability, and thus may prevent arch collapse in the long term.
PMID- 28416099
TI - Statin use and risk of new-onset diabetes: A meta-analysis of observational
studies.
AB - BACKGROUND AND AIMS: Meta-analyses of randomized control trials investigating the
association between incident diabetes and statin use showed an increased risk of
new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short
follow-up period, unpowered sample size, and lack of pre-specified diagnostic
criteria for diabetes detection could be responsible of an underestimation of
this risk. We conducted a meta-analysis of published observational studies to
evaluate the association between statins use and risk of NOD. METHODS AND
RESULTS: PubMed, EMBASE and MEDLINE databases were searched from inception to
June 30, 2016 for cohort and case-control studies with risk of NOD in users vs
nonusers, on >=1000 subjects followed-up for >=1 year. Two review authors
assessed study eligibility and risk of bias and undertook data extraction
independently. Pooled estimates were calculated by a random-effects model and
between-study heterogeneity was tested and measured by I2 index. Furthermore,
stratified analyses and the evaluation of publication bias were performed.
Finally, the meta-analysis included 20 studies, 18 cohort and 2 case-control
studies. Overall, NOD risk was higher in statin users than nonusers (RR 1.44; 95%
CI 1.31-1.58). High between-study heterogeneity (I2 = 97%) was found. Estimates
for all single statins showed a class effect, from rosuvastatin (RR 1.61; 1.30
1.98) to simvastatin (RR 1.38; 1.19-1.61). CONCLUSIONS: The present meta-analysis
confirms and reinforces the evidence of a diabetogenic effect by statins
utilization. These observations confirm the need of a rigorous monitoring of
patients taking statins, in particular pre-diabetic patients or patients
presenting with established risk factors for diabetes.
PMID- 28416100
TI - Synthesis and biological evaluation of largazole zinc-binding group analogs.
AB - Histone acetylation is an extensively investigated post-translational
modification that plays an important role as an epigenetic regulator. It is
controlled by histone acetyl transferases (HATs) and histone deacetylases
(HDACs). The overexpression of HDACs and consequent hypoacetylation of histones
have been observed in a variety of different diseases, leading to a recent focus
of HDACs as attractive drug targets. The natural product largazole is one of the
most potent natural HDAC inhibitors discovered so far and a number of largazole
analogs have been prepared to define structural requirements for its HDAC
inhibitory activity. However, previous structure-activity relationship studies
have heavily investigated the macrocycle region of largazole, while there have
been only limited efforts to probe the effect of various zinc-binding groups
(ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with
various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of
the analogs tested were as potent or selective as largazole, the Zn2+-binding
affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect
that our findings will aid in building a deeper understanding of the role of ZBGs
in HDAC inhibition as well as provide an important basis for the future
development of new largazole analogs with non-thiol ZBGs as novel therapeutics
for cancer.
PMID- 28416101
TI - N-Substituted and ring opened saccharin derivatives selectively inhibit
transmembrane, tumor-associated carbonic anhydrases IX and XII.
AB - A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl
moieties, as well as some ring opened derivatives were prepared and investigated
as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The
widespread cytosolic isoforms CA I and II were not inhibited by these
sulfonamides whereas transmembrane, tumor-associated ones were effectively
inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA
XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides
is unknown for the moment, the good efficacy and especially selectivity for the
inhibition of the tumor-associated over the cytosolic, widespread isoforms, make
these derivatives of considerable interest as enzyme inhibitors with various
pharmacologic applications.
PMID- 28416102
TI - Synthesis, biochemical evaluation, and molecular modeling studies of aryl and
arylalkyl di-n-butyl phosphates, effective butyrylcholinesterase inhibitors.
AB - A series of dialkyl aryl phosphates and dialkyl arylalkyl phosphates were
synthesized. Their inhibitory activities were evaluated against
acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The di-n-butyl
phosphate series consistently displayed selective inhibition of BChE over AChE.
The most potent inhibitors of butyrylcholinesterase were di-n-butyl-3,5
dimethylphenyl phosphate (4b) [KI=1.0+/-0.4MUM] and di-n-butyl 2-naphthyl
phosphate (5b) [KI=1.9+/-0.4MUM]. Molecular modeling was used to uncover three
subsites within the active site gorge that accommodate the three substituents
attached to the phosphate group. Phosphates 4b and 5b were found to bind to these
three subsites in analogous fashion with the aromatic groups in both analogs
being accommodated by the "lower region," while the lone pairs on the PO oxygen
atoms were oriented towards the oxyanion hole. In contrast, di-n-butyl-3,4
dimethylphenyl phosphate (4a) [KI=9+/-1MUM], an isomer of 4b, was found to orient
its aromatic group in the "upper left region" subsite as placement of this group
in the "lower region" resulted in significant steric hindrance by a ridge-like
region in this subsite. Future studies will be designed to exploit these features
in an effort to develop inhibitors of higher inhibitory strength against
butyrylcholinesterase.
PMID- 28416098
TI - Ideal cardiovascular health and inflammation in European adolescents: The HELENA
study.
AB - BACKGROUND AND AIMS: Inflammation plays a key role in atherosclerosis and this
process seems to appear in childhood. The ideal cardiovascular health index
(ICHI) has been inversely related to atherosclerotic plaque in adults. However,
evidence regarding inflammation and ICHI in adolescents is scarce. The aim is to
assess the association between ICHI and inflammation in European adolescents.
METHODS AND RESULTS: As many as 543 adolescents (251 boys and 292 girls) from the
Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, a cross
sectional multi-center study including 9 European countries, were measured. C
reactive protein (CRP), complement factors C3 and C4, leptin and white blood cell
counts were used to compute an inflammatory score. Multilevel linear models and
multilevel logistic regression were used to assess the association between ICHI
and inflammation controlling by covariates. Higher ICHI was associated with a
lower inflammatory score, as well as with several individual components, both in
boys and girls (p < 0.01). In addition, adolescents with at least 4 ideal
components of the ICHI had significantly lower inflammatory score and lower
levels of the study biomarkers, except CRP. Finally, the multilevel logistic
regression showed that for every unit increase in the ICHI, the probability of
having an inflammatory profile decreased by 28.1% in girls. CONCLUSION: Results
from this study suggest that a better ICHI is associated with a lower
inflammatory profile already in adolescence. Improving these health behaviors,
and health factors included in the ICHI, could play an important role in CVD
prevention.
PMID- 28416103
TI - A new "twist" on right heart failure with left ventricular assist systems.
AB - Despite significant efforts to predict and prevent right heart failure, it
remains a leading cause of morbidity and mortality after implantation of left
ventricular assist systems (LVAS). In this Perspective, we review the
underappreciated anatomic and physiologic principles that govern the relationship
between left and right heart function and contribute to this phenomenon. This
includes the importance of considering the right ventricle (RV) and pulmonary
arterial circuit as a coupled system; the contribution of the left ventricle (LV)
to RV contractile function and the potential negative impact of acutely unloading
the LV; the influence of the pericardium and ventricular twist on septal
function; the role of RV deformation in reduced mechanical efficiency after
device placement; and the potential of ongoing stressors of an elevated right
sided preload. We believe an appreciation of these complex issues is required to
fully understand the expression of the unique phenotypes of right heart failure
after LVAS implantation and for developing better prognostic and therapeutic
strategies.
PMID- 28416104
TI - Multilocular cystic renal cell carcinoma: pathological t staging makes no
difference to favorable outcomes and should be reclassified. Bhatt JR, Jewett MA,
Richard PO, Kawaguchi S, Timilshina N, Evans A, Alibhai S, Finelli A.J Urol.
November 2016;196(5):1350-1355.
AB - OBJECTIVE: We evaluated survival outcomes of cystic/multilocular cystic renal
cell carcinomas in a long-term population-based study based on size and
pathological tumor stage. MATERIALS AND METHODS: We, retrospectively, reviewed a
provincial cancer registry of all histologically proven cases of multilocular
cystic renal cancers treated surgically between 1995 and 2008. All cases of
cystic necrosis were excluded from study. Primary end points were overall- and
cancer-specific survival estimated using Kaplan-Meier curves. Cox proportional
hazards models of univariable and multivariable analyses were used to assess for
factors associated with survival. RESULTS: Of 172 cases of cystic renal cancers
168 with complete data were analyzed, of which 98% were multilocular cystic.
Median patient age at treatment was 55 years and 58% of the patients were male.
More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most
cases were low Fuhrman grade (1-2). At a median follow-up of 9.75-years overall-
and cancer-specific survival was 82.1% and 100%, respectively. No difference was
noted in higher pathological T stage, size, or grade. Limitations inherent in
population-based studies include under ascertainment of cause of death, lack of
data on histologically benign cysts that are treated surgically and a lack of
central pathology review. CONCLUSIONS: Multilocular cystic renal cell carcinoma
has an excellent prognosis, which remains unchanged regardless of tumor size or
pathological T stage. This suggests a strong case for nephron and adrenal sparing
surgery when indicated, and nonsurgical management when feasible. As
postoperative follow-up protocols are dictated by staging, we propose that for
this entity pathological T staging should be abandoned or reassigned as pT1c to
guide clinicians.
PMID- 28416105
TI - Do clear cell papillary renal cell carcinomas have malignant potential? Diolombi
ML, Cheng L, Argani P, Epstein JI.Am J Surg Pathol. December 2015;39(12):1621
1634.
AB - There have been no recurrences or metastases of clear cell papillary renal cell
carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language
literature. We identified all our cases of CCPRCC (1990-2013), reviewing all
cases that preceded the formal designation of the entity. Immunohistochemical
stains were performed on 32 cases during their initial workup. In addition,
stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one
with atypical follow-up and the other with a more compact morphology, although
not performed initially. An extended panel with AMACR, CD10, and renal cell
carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in
situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case
and on another clinically presumed metastatic tumor. In classic cases,
immunohistochemical staining was not performed. Fifty-eight patients (31 women;
27 men) with follow-up data were included in our study; 39 cases were from our
consult service. The patients' ages ranged from 36 to 83 years. Thirty-five
patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of
which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1
disease (size range: 0.2-8cm), 2 patients presented with pT2 disease (8.5 and
10.3cm), 1 patient presented with pT3 disease (6.5cm sarcomatoid RCC focally
extending out of the kidney), and pathologic stage was unavailable in 2 cases.
Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2
cryoablations, and 1 cyst ablation. The resection margins were negative in all
but one case, with this case disease free after a 26-month period. Two patients
had intraoperative tumor disruption and were disease free at 9 and 34 months.
Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC).
Mean follow-up time was 21 months (range: 1-175 months), with all but 3 patients
having no evidence of disease. One patient was presumed to have contralateral
disease on the basis of imaging findings and is alive and well 37 months after
multiple partial nephrectomies. Metastatic disease to the lung was clinically
presumed in 1 patient in whom a higher-grade lesion may have been missed during
sampling of the predominantly cystic pT1b tumor and tissue confirmation of the
metastases was not obtained. Another case presented with multiple skeletal and
pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The
patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary
metastatic disease 13 months after resection of the renal tumor. Our study, the
largest to date with follow-up, along with others, suggests that pure CCPRCC is
an indolent tumor and should be renamed "clear cell papillary neoplasm of low
malignant potential" to reflect their biology.
PMID- 28416106
TI - Categorizing renal oncocytic neoplasms on core needle biopsy: a morphologic and
immunophenotypic study of 144 cases with clinical follow-up. Alderman MA,
Daignault S, Wolf JS Jr, Palapattu GS, Weizer AZ, Hafez KS, Kunju LP, Wu AJ. Hum
Pathol.September 2016;55:1-10.
AB - There is limited literature on renal oncocytic neoplasms diagnosed on core
biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were,
retrospectively, reviewed. Morphologic features and an immunohistochemical panel
of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis,
statistical analysis including a random forest classification, and follow-up were
recorded. The postimmunohistochemical diagnoses of 144 renal oncocytic core
biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and
cannot exclude RCC (21%). Diagnosis was revised following immunohistochemistry in
7% of cases. The most common features for oncocytoma (excluding dense granular
cytoplasm) were nested architecture, edematous stroma, binucleation and tubular
architecture; the most common features for favor RCC were sheet-like
architecture, nuclear pleomorphism, papillary architecture, and prominent cell
borders. High nuclear grade, necrosis, extensive papillary architecture,
raisinoid nuclei, and frequent mitoses were not seen in oncocytomas. Comparing
the pathologist and random forest classification, the overall out-of-bag estimate
of classification error dropped from 23% to 13% when favor RCC and cannot exclude
RCC was combined into 1 category. Resection was performed in 19% (28 cases) with
a 94% concordance (100% of favor RCC biopsies and 90% of cannot exclude RCC
biopsies confirmed as RCC; 83% of favor oncocytomas confirmed); ablation in 23%;
and surveillance in 46%. Follow-up was available in 92% (median follow-up, 33
months) with no adverse outcomes. Renal oncocytic neoplasms comprise a
significant subset (16%) of all core biopsies, and the majority (78%) can be
classified as favor oncocytoma or favor RCC.
PMID- 28416107
TI - Characteristics of the peritumoral pseudocapsule vary predictably with histologic
subtype of T1 renal neoplasms. Jacob JM, Williamson SR, Gondim DD, Leese JA,
Terry C, Grignon DJ, Boris RS.Urology. November 2015;86(5):956-961.
AB - OBJECTIVE: To determine characteristics of the peritumoral pseudocapsule (PC)
between renal tumor subtypes. METHODS: The peritumoral PCs of 160 pT1 renal
tumors were examined, including 60 clear cell renal cell carcinomas (RCCs), 50
papillary RCCs, 25 chromophobe RCCs, and 25 oncocytoma. Pathologic features
(presence or absence of PC, mean thickness, continuity, and invasion by tumor)
were analyzed. PC thickness was measured using an ocular micrometer to the
nearest 1/10mm. RESULTS: A complete PC was found in 77% of clear cell tumors, 74%
of papillary, 28% of chromophobe, and 4% of oncocytomas. Tumor PC was present but
incomplete in 18% of clear cell, 18% of papillary, 44% of chromophobe, and 56% of
oncocytoma. The PC was entirely absent in no clear cell tumors, 6% of papillary,
28% of chromophobe, and 40% of oncocytoma. Mean PC thickness and presence of
invasion beyond the PC differed significantly by tumor subtype. Clear cell RCC
possessed the thickest PC showing invasion through the capsule in 8% of tumors
compared to 30% of papillary tumors. Complete PC invasion was not seen in
chromophobe RCC or renal oncocytoma. Oncocytoma and chromophobe RCC
characteristically exhibited an incomplete or absent PC. CONCLUSIONS: The
characteristics of peritumoral PC vary predictably with histologic subtype of
renal neoplasms. Clear cell RCC shows the most consistent PC, with a lower rate
of invasion beyond it compared to papillary RCC. Chromophobe and oncocytoma
characteristically have an incomplete or absent PC.
PMID- 28416108
TI - Tumor necrosis adds prognostically significant information to grade in clear cell
renal cell carcinoma: A study of 842 consecutive cases from a single institution.
Khor LY, Dhakal HP, Jia X, Reynolds JP, McKenney JK, Rini BI, Magi-Galluzzi C,
Przybycin CG.Am J Surg Pathol. September 2016;40(9):1224-1231.
AB - Tumor necrosis has been shown to be an independent predictor of adverse outcome
in renal cell carcinoma. A modification of the International Society of
Urological Pathology (ISUP) grading system for renal cell carcinomas has recently
been proposed, which incorporates the presence of tumor necrosis into grade. The
investigators proposing this system found that necrosis added significant
prognostic information to ISUP grade. We attempted to describe our experience
with the effect of tumor necrosis in relationship to nuclear grade by reviewing
the slides from a large consecutive series of localized clear cell renal cell
carcinomas from our institution and obtaining long-term clinical follow-up
information (overall survival). Of the 842 clear cell renal cell carcinomas
reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and
140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. A
total of 547 (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%)
were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2
months (range: 0.12-273.6), and 310 (36.8%) patients died. On univariable
analysis, there was no significant difference in outcome for tumors of ISUP
grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade
4 and necrosis were significant predictors of overall survival on multivariable
analysis. When the recently proposed modified grading system incorporating tumor
necrosis was applied to our data, there was no significant difference in overall
survival between patients with modified grade 1 tumors and those with modified
grade 2 tumors (P = 0.31); however, there was a statistically significant
difference between patients with modified grade 1 or 2 tumors and those with
modified grade 3 tumors (P = 0.04), and a substantial difference in outcome
between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a
recursive partitioning approach was applied to our data, patients of a given ISUP
grade could be further prognostically separated according to the presence or
absence of necrosis and could be divided into 3 statistically significant
prognostic groups: (1) non-necrotic ISUP grade 1 to 3 tumors, (2) ISUP grade 1 to
3 tumors with necrosis and ISUP grade 4 tumors with<10% necrosis, and (3) ISUP
grade 4 tumors with>10% necrosis. In conclusion, our study shows that tumor
necrosis adds additional prognostic information to ISUP grade and that
quantification of necrosis can further stratify patients with ISUP grade 4
tumors.
PMID- 28416109
TI - Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy
for High Risk Renal Tumors. Shah PH, Moreira DM, Okhunov Z, Patel VR, Chopra S,
Razmaria AA, Alom M, George AK, Yaskiv O, Schwartz MJ, Desai M, Vira MA,
Richstone L, Landman J, Shalhav AL, Gill I, Kavoussi LR. J Urol. 2016
Aug;196(2):327-34.
AB - PURPOSE: The clinical significance of a positive surgical margin after partial
nephrectomy remains controversial. The association between positive margin and
risk of disease recurrence in patients with clinically localized renal neoplasms
undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A
retrospective multi-institutional review of 1,240 patients undergoing partial
nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013
was performed. Recurrence-free survival was estimated using the Kaplan-Meier
method and evaluated as a function of positive surgical margin with the log rank
test and Cox models adjusting for tumor size, grade, histology, pathological
stage, focality and laterality. The relationship between positive margin and risk
of relapse was evaluated independently for pathological high risk (pT2-3a or
Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups.
RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients.
Recurrence developed in 69 (5.6%) patients during a median followup of 33 months,
including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III
IV). A positive margin was associated with an increased risk of relapse on
multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of
recurrence. In a stratified analysis based on pathological features, a positive
surgical margin was significantly associated with a higher risk of recurrence in
cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low
risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins
after partial nephrectomy increase the risk of disease recurrence, primarily in
patients with adverse pathological features.
PMID- 28416110
TI - Structural Basis for Kinase-Mediated Macrolide Antibiotic Resistance.
AB - The macrolides are a class of antibiotic, characterized by a large macrocyclic
lactone ring that can be inactivated by macrolide phosphotransferase enzymes. We
present structures for MPH(2')-I and MPH(2')-II in the apo state, and in complex
with GTP analogs and six different macrolides. These represent the first
structures from the two main classes of macrolide phosphotransferases. The
structures show that the enzymes are related to the aminoglycoside
phosphotransferases, but are distinguished from them by the presence of a large
interdomain linker that contributes to an expanded antibiotic binding pocket.
This pocket is largely hydrophobic, with a negatively charged patch located at a
conserved aspartate residue, rationalizing the broad-spectrum resistance
conferred by the enzymes. Complementary mutation studies provide insights into
factors governing substrate specificity. A comparison with macrolides bound to
their natural target, the 50S ribosome, suggests avenues for next-generation
antibiotic development.
PMID- 28416111
TI - Structural Analysis Reveals Features of Ribosome Assembly Factor Nsa1/WDR74
Important for Localization and Interaction with Rix7/NVL2.
AB - Ribosome assembly is a complex process that requires hundreds of essential
assembly factors, including Rix7 (NVL2 in mammals) and Nsa1 (WDR74 in mammals).
Rix7 is a type II double ring, AAA-ATPase, which is closely related to the well
known Cdc48/p97. Previous studies in Saccharomyces cerevisiae suggest that Rix7
mediates the release of Nsa1 from nucleolar pre-60S particles; however, the
underlying mechanisms of this release are unknown. Through multiple structural
analyses we show that S. cerevisiae Nsa1 is composed of an N-terminal seven
bladed WD40 domain followed by a lysine-rich C terminus that extends away from
the WD40 domain and is required for nucleolar localization. Co
immunoprecipitation assays with the mammalian homologs identified a well
conserved interface within WDR74 that is important for its association with NVL2.
We further show that WDR74 associates with the D1 AAA domain of NVL2, which
represents a novel mode of binding of a substrate with a type II AAA-ATPase.
PMID- 28416113
TI - Early Evolution of Specialized Termitophily in Cretaceous Rove Beetles.
AB - Termitophiles, symbionts that live in termite nests, include a wide range of
morphologically and behaviorally specialized organisms. Complex adaptive
mechanisms permit these animals to integrate into societies and to exploit their
controlled physical conditions and plentiful resources, as well as to garner
protection inside termite nests. An understanding of the early evolution of
termitophily is challenging owing to a scarcity of fossil termitophiles, with all
known reliable records occurring from the Miocene (approximately 19 million years
ago [mya]) [1-6], and an equivocal termitophile belonging to the largely free
living Mesoporini from the mid-Cretaceous [7]. Here we report the oldest,
morphologically specialized, and obligate termitophiles from mid-Cretaceous
Burmese amber (99 mya). Cretotrichopsenius burmiticus gen. et sp. nov. belongs to
Trichopseniini, a group of distinctive termitophilous aleocharine rove beetles,
all of which possess specialized swollen or horseshoe-crab-shaped body plans.
Cretotrichopsenius display the protective horseshoe-crab-shaped body form typical
of many modern termitophiles, with concealed head and antennae and strong
posteriorly directed abdominal setae. Cretotrichopsenius represent the earliest
definitive termitophiles, shedding light on host associations in the early
evolution of termite societies. The fossil reveals that ancient termite societies
were quickly invaded by beetles and by multiple independent lineages of social
parasites over the subsequent eons.
PMID- 28416112
TI - Flexibility and Design: Conformational Heterogeneity along the Evolutionary
Trajectory of a Redesigned Ubiquitin.
AB - Although protein design has been used to introduce new functions, designed
variants generally only function as well as natural proteins after rounds of
laboratory evolution. One possibility for this pattern is that designed mutants
frequently sample nonfunctional conformations. To test this idea, we exploited
advances in multiconformer modeling of room-temperature X-ray data collection on
redesigned ubiquitin variants selected for increasing binding affinity to the
deubiquitinase USP7. Initial core mutations disrupt natural packing and lead to
increased flexibility. Additional, experimentally selected mutations quenched
conformational heterogeneity through new stabilizing interactions. Stabilizing
interactions, such as cation-pi stacking and ordered waters, which are not
included in standard protein design energy functions, can create specific
interactions that have long-range effects on flexibility across the protein. Our
results suggest that increasing flexibility may be a useful strategy to escape
local minima during initial directed evolution and protein design steps when
creating new functions.
PMID- 28416114
TI - Invariance of Initiation Mass and Predictability of Cell Size in Escherichia
coli.
AB - It is generally assumed that the allocation and synthesis of total cellular
resources in microorganisms are uniquely determined by the growth conditions.
Adaptation to a new physiological state leads to a change in cell size via
reallocation of cellular resources. However, it has not been understood how cell
size is coordinated with biosynthesis and robustly adapts to physiological
states. We show that cell size in Escherichia coli can be predicted for any
steady-state condition by projecting all biosynthesis into three measurable
variables representing replication initiation, replication-division cycle, and
the global biosynthesis rate. These variables can be decoupled by selectively
controlling their respective core biosynthesis using CRISPR interference and
antibiotics, verifying our predictions that different physiological states can
result in the same cell size. We performed extensive growth inhibition
experiments, and we discovered that cell size at replication initiation per
origin, namely the initiation mass or unit cell, is remarkably invariant under
perturbations targeting transcription, translation, ribosome content, replication
kinetics, fatty acid and cell wall synthesis, cell division, and cell shape.
Based on this invariance and balanced resource allocation, we explain why the
total cell size is the sum of all unit cells. These results provide an
overarching framework with quantitative predictive power over cell size in
bacteria.
PMID- 28416115
TI - In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals
Differences between Functional Classes of Motoneurons in Zebrafish.
AB - The interplay between binding and unbinding of synaptic receptor proteins at
synapses plays an important role in determining receptor concentration and
synaptic strength, with known links between changes in binding kinetics and
synaptic plasticity. The regulation of such kinetics may subserve the specific
functional requirements of neurons in intact circuits. However, the majority of
studies of synaptic turnover kinetics have been performed in cultured neurons
outside the context of normal circuits, and synaptic receptor turnover has not
been measured at individual synaptic sites in vivo. We quantified the
distribution of glycinergic receptor dynamics using fluorescence recovery after
photoconversion of synapses in intact zebrafish and correlated recovery kinetics
to synaptic volume in two functionally distinct classes of cells: primary and
secondary motoneurons. The rate of fluorescence recovery after photoconversion
decreased with synaptic volume in both types of motoneurons, with larger synapses
having slower recovery. Primary motoneurons had both larger synapses and
associated slower recovery times than secondary motoneurons. Our results suggest
that synaptic kinetics are regulated in concert with synaptic sizes and reflect
the functional role played by neurons within their circuit.
PMID- 28416116
TI - Activation of a Plant NLR Complex through Heteromeric Association with an
Autoimmune Risk Variant of Another NLR.
AB - When independently evolved immune receptor variants meet in hybrid plants, they
can activate immune signaling in the absence of non-self recognition. Such
autoimmune risk alleles have recurrently evolved at the DANGEROUS MIX2 (DM2)
nucleotide-binding domain and leucine-rich repeat (NLR)-encoding locus in A.
thaliana. One of these activates signaling in the presence of a particular
variant encoded at another NLR locus, DM1. We show that the risk variants of DM1
and DM2d NLRs signal through the same pathway that is activated when plant NLRs
recognize non-self elicitors. This requires the P loops of each protein and
Toll/interleukin-1 receptor (TIR)-domain-mediated heteromeric association of DM1
and DM2d. DM1 and DM2d each resides in a multimeric complex in the absence of
signaling, with the DM1 complex shifting to higher molecular weight when
heteromerizing DM2 variants are present. The activation of the DM1 complex
appears to be sensitive to the conformation of the heteromerizing DM2 variant.
Autoimmunity triggered by interaction of this NLR pair thus suggests that
activity of heteromeric NLR signaling complexes depends on the sum of activation
potentials of partner NLRs.
PMID- 28416117
TI - Rapid Spatial Learning Controls Instinctive Defensive Behavior in Mice.
AB - Instinctive defensive behaviors are essential for animal survival. Across the
animal kingdom, there are sensory stimuli that innately represent threat and
trigger stereotyped behaviors such as escape or freezing [1-4]. While innate
behaviors are considered to be hard-wired stimulus-responses [5], they act within
dynamic environments, and factors such as the properties of the threat [6-9] and
its perceived intensity [1, 10, 11], access to food sources [12-14], and
expectations from past experience [15, 16] have been shown to influence defensive
behaviors, suggesting that their expression can be modulated. However, despite
recent work [2, 4, 17-21], little is known about how flexible mouse innate
defensive behaviors are and how quickly they can be modified by experience. To
address this, we have investigated the dependence of escape behavior on learned
knowledge about the spatial environment and how the behavior is updated when the
environment changes acutely. Using behavioral assays with innately threatening
visual and auditory stimuli, we show that the primary goal of escape in mice is
to reach a previously memorized shelter location. Memory of the escape target can
be formed in a single shelter visit lasting less than 20 s, and changes in the
spatial environment lead to a rapid update of the defensive action, including
changing the defensive strategy from escape to freezing. Our results show that
although there are innate links between specific sensory features and defensive
behavior, instinctive defensive actions are surprisingly flexible and can be
rapidly updated by experience to adapt to changing spatial environments.
PMID- 28416118
TI - A Magnetic Map Leads Juvenile European Eels to the Gulf Stream.
AB - Migration allows animals to track the environmental conditions that maximize
growth, survival, and reproduction [1-3]. Improved understanding of the
mechanisms underlying migrations allows for improved management of species and
ecosystems [1-4]. For centuries, the catadromous European eel (Anguilla anguilla)
has provided one of Europe's most important fisheries and has sparked
considerable scientific inquiry, most recently owing to the dramatic collapse of
juvenile recruitment [5]. Larval eels are transported by ocean currents
associated with the Gulf Stream System from Sargasso Sea breeding grounds to
coastal and freshwater habitats from North Africa to Scandinavia [6, 7]. After a
decade or more, maturing adults migrate back to the Sargasso Sea, spawn, and die
[8]. However, the migratory mechanisms that bring juvenile eels to Europe and
return adults to the Sargasso Sea remain equivocal [9, 10]. Here, we used a
"magnetic displacement" experiment [11, 12] to show that the orientation of
juvenile eels varies in response to subtle differences in magnetic field
intensity and inclination angle along their marine migration route. Simulations
using an ocean circulation model revealed that even weakly swimming in the
experimentally observed directions at the locations corresponding to the magnetic
displacements would increase entrainment of juvenile eels into the Gulf Stream
System. These findings provide new insight into the migration ecology and
recruitment dynamics of eels and suggest that an adaptive magnetic map, tuned to
large-scale features of ocean circulation, facilitates the vast oceanic
migrations of the Anguilla genus [7, 13, 14].
PMID- 28416119
TI - The Head-Direction Signal Plays a Functional Role as a Neural Compass during
Navigation.
AB - The rat limbic system contains head direction (HD) cells that fire according to
heading in the horizontal plane, and these cells are thought to provide animals
with an internal compass. Previous work has found that HD cell tuning correlates
with behavior on navigational tasks, but a direct, causal link between HD cells
and navigation has not been demonstrated. Here, we show that pathway-specific
optogenetic inhibition of the nucleus prepositus caused HD cells to become
directionally unstable under dark conditions without affecting the animals'
locomotion. Then, using the same technique, we found that this decoupling of the
HD signal in the absence of visual cues caused the animals to make directional
homing errors and that the magnitude and direction of these errors were in a
range that corresponded to the degree of instability observed in the HD signal.
These results provide evidence that the HD signal plays a causal role as a neural
compass in navigation.
PMID- 28416120
TI - Diabetes Complications Severity Index (DCSI)-Update and ICD-10 translation.
AB - AIMS: The Diabetes Complications Severity Index (DCSI) converts diagnostic codes
and laboratory results into a 14-level metric quantifying the long-term effects
of diabetes on seven body systems. Adoption of the International Classification
of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) necessitates
translation from ICD-9-CM and creates refinement opportunities. METHODS: ICD-9
codes for secondary and primary diabetes plus all five ICD-10 diabetes categories
were incorporated into an updated tool. Additional modifications were made to
improve the accuracy of severity assignments. SUBJECTS: The tools were tested in
a Medicare Advantage population. RESULTS: In the type 2 subpopulation, prevalence
steadily declined with increasing score according to the updated DCSI tool,
whereas the original tool resulted in an aberrant local prevalence peak at DCSI =
2. In the type 1 subpopulation, score prevalence was greater in type 1 versus
type 2 subpopulations (3 versus 0) according to both instruments. Both
instruments predicted current-year inpatient admissions risk and near-future
mortality, using either purely ICD-9 data or a mix of ICD-9 and ICD-10 data.
DISCUSSION: While the performance of the tool with purely ICD-10 data has yet to
be evaluated, this updated tool makes assessment of diabetes patient severity and
complications possible in the interim.
PMID- 28416121
TI - Silent coronary heart disease in patients with type 2 diabetes: application of a
screening approach in a follow-up study.
AB - AIMS: The cost-effectiveness of screening for silent coronary heart disease (CHD)
in type 2 diabetes (DM2) is still debated. METHODS: We applied a diagnostic
algorithm for silent CHD detection, in a cohort of 102 asymptomatic DM2 subjects
(57+/-7years), attending 5 Italian outpatient clinics, to verify its predictive
value. The risk of silent CHD was calculated considering classical risk factors,
and presence of microangiopathy/macroangiopathy. Patients were divided in 3
groups, i.e. group 1: normal ECG and low silent CHD risk; group 2: abnormal ECG,
irrespective of silent CHD risk; group 3: high silent CHD risk, irrespective of
ECG. To group 2 and 3, a functional test was recommended and performed in 78% of
patients. RESULTS: Silent CHD prevalence was similar in group 2 and 3 (25 vs. 17%
respectively; p=0.495). However, evaluating the entire cohort, a significant
higher prevalence of silent CHD was observed in subjects with abnormal vs. normal
ECG (23 vs. 4%; P=0.004), but not in subjects with high vs. low pre-test silent
CHD risk (14 vs. 9%; p=0.472). CONCLUSIONS: An abnormal ECG was a strong,
independent predictor of silent CHD (OR 8.9; CI 1.27-62.5; p=0.028) in DM2.
Therefore, a functional stress testing should be considered in DM2 patients with
ECG abnormalities.
PMID- 28416123
TI - Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung
Cancer: A Systematic Review.
AB - Second-line treatment options are limited for patients with advanced non-small
cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents
docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors
are a new class of treatment that have shown durable overall radiologic response
rates and have been well tolerated. The objective of this systematic review was
to investigate the efficacy of immune checkpoint inhibitors compared with other
chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were
searched for randomized controlled trials comparing treatment with immune
checkpoint inhibitors against treatment with chemotherapy in patients with stage
IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were
included. A significant overall survival benefit of second-line nivolumab
(nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77;
P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line
atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line
pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive
tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008;
pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line
pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy
was found. The adverse effects were mainly higher in the chemotherapy arms. For
patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival
outweighed the harms and supported the use of first-line pembrolizumab (in
patients with >= 50% PD-L1-positive tumors) or second-line nivolumab,
atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors).
PMID- 28416122
TI - Patients with a resected pancreatic mucinous cystic neoplasm have a better
prognosis than patients with an intraductal papillary mucinous neoplasm: A large
single institution series.
AB - BACKGROUND/OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors
distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the
presence of ovarian-type stroma. Historical outcomes for MCNs vary due to
previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This
study seeks to characterize and clarify the clinical features and long-term
outcomes of MCNs versus IPMNs in the largest single-institution series of
pathology-confirmed MCNs to date. METHODS: We compared 142 MCNs and 746 IPMNs
resected at a single institution. MCNs were reviewed for confirmation of ovarian
type stroma and reclassified according to current WHO guidelines. RESULTS: MCNs
presented almost exclusively in middle-aged women (median 47.5 years, 96.5%
female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas
(92.1%). IPMNs were distributed equally by sex in an older population (median
69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared
with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1%
vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs
(9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs.
Patients with an MCN-associated invasive carcinoma had a much better prognosis
than did patients with an IPMN-associated invasive carcinoma with 10-year disease
specific survival of 79.6% versus 27.2%, respectively. CONCLUSION: MCNs have a
stereotypical clinical profile that is readily distinguishable from IPMNs based
on demographic features, imaging, and pathology. Most MCNs are noninvasive and
curable with surgical resection. Prognosis remains excellent even for invasive
disease with 10-year survival approaching 80% following resection.
PMID- 28416124
TI - Assessment of the External Validity of the National Comprehensive Cancer Network
and European Society for Medical Oncology Guidelines for Non-Small-Cell Lung
Cancer in a Population of Patients Aged 80 Years and Older.
AB - Non-small-cell lung cancer (NSCLC) is a disease of the elderly, who are under
represented in clinical trials. This challenges the external validity of the
evidence base for its management and of current guidelines, that we evaluated in
a population of older patients. We retrieved randomized clinical trials (RCTs)
supporting the guidelines and identified 18 relevant topics. We matched a cohort
of NSCLC patients aged older than 80 years from the Moffitt Cancer Center
database with the studies' eligibility criteria to check their qualification for
at least 2 studies. Eligibility > 60% was rated full validity, 30% to 60% partial
validity, and < 30% limited validity. We obtained data from 760 elderly patients
in stage-adjusted groups and collected 244 RCTs from the National Comprehensive
Cancer Network (NCCN) and 148 from the European Society for Medical Oncology
(ESMO) guidelines. External validity was deemed insufficient for neoadjuvant
chemotherapy in stage III disease (27.37% and 25.26% of patients eligible for
NCCN and ESMO guidelines, respectively) and use of bevacizumab (13.86% and 16.27%
of patients eligible). For ESMO guidelines, it was inadequate regarding double
agent chemotherapy (25.90% of patients eligible), its duration (24.10%) and
therapy for Eastern Cooperative Oncology Group performance status 2 patients
(17.74%). For NCCN guidelines external validity was lacking for neoadjuvant
chemoradiotherapy in stage IIIA disease (25.86% of patients eligible). Our
analysis highlighted the effect of RCT eligibility criteria on guidelines'
external validity in elderly patients. Eligibility criteria should be carefully
considered in trial design and more studies that do not exclude elderly patients
should be included in guidelines.
PMID- 28416125
TI - Efficacy of pretreating oil palm fronds with an acid-base mixture catalyst.
AB - Oil palm fronds are abundant but recalcitrant to chemical pretreatment. Herein,
an acid-base mixture was applied as a catalyst to efficiently pretreat oil palm
fronds. Optimized conditions for the pretreatment were a 0.1M acidic acid-base
mixture and 3min ramping to 190 degrees C and 12min holding. The oil palm fronds
pretreated and washed with the acid-base mixture exhibited an enzymatic
digestibility of 85% by 15 FPU Accellerase 1000/g glucan after 72h hydrolysis,
which was significantly higher than the enzymatic digestibilities obtained by
acid or alkali pretreatment alone. This could be attributed to the synergistic
actions of the acid and base, producing an 87% glucose recovery with 100% and
40.3% removal of xylan and lignin, respectively, from the solids. Therefore, an
acid-base mixture can be a feasible catalyst to deconstruct oil palm fronds for
sugar production.
PMID- 28416126
TI - Biokinetic model-based multi-objective optimization of Dunaliella tertiolecta
cultivation using elitist non-dominated sorting genetic algorithm with
inheritance.
AB - Algal model based multi-objective optimization using elitist non-dominated
sorting genetic algorithm with inheritance was carried out for batch cultivation
of Dunaliella tertiolecta using NPK-fertilizer. Optimization problems involving
two- and three-objective functions were solved simultaneously. The objective
functions are: maximization of algae-biomass and lipid productivity with
minimization of cultivation time and cost. Time variant light intensity and
temperature including NPK-fertilizer, NaCl and NaHCO3 loadings are the important
decision variables. Algal model involving Monod/Andrews adsorption kinetics and
Droop model with internal nutrient cell quota was used for optimization studies.
Sets of non-dominated (equally good) Pareto optimal solutions were obtained for
the problems studied. It was observed that time variant optimal light intensity
and temperature trajectories, including optimum NPK fertilizer, NaCl and NaHCO3
concentration has significant influence to improve biomass and lipid productivity
under minimum cultivation time and cost. Proposed optimization studies may be
helpful to implement the control strategy in scale-up operation.
PMID- 28416127
TI - Experimental and modelling of Arthrospira platensis cultivation in open raceway
ponds.
AB - In this study, the growth of Arthrospira platensis was studied in an open raceway
pond. Furthermore, dynamic model for algae growth and CFD modelling of
hydrodynamics in open raceway pond were developed. The dynamic behaviour of the
algal system was developed by solving mass balance equations of various
components, considering light intensity and gas-liquid mass transfer. A CFD
modelling of the hydrodynamics of open raceway pond was developed by solving mass
and momentum balance equations of the liquid medium. The prediction of algae
concentration from the dynamic model was compared with the experimental data. The
hydrodynamic behaviour of the open raceway pond was compared with the literature
data for model validation. The model predictions match the experimental findings.
Furthermore, the hydrodynamic behaviour and residence time distribution in our
small raceway pond were predicted. These models can serve as a tool to assess the
pond performance criteria.
PMID- 28416128
TI - Carbamazepine responsive generalized dystonia in Fahr's disease.
PMID- 28416129
TI - Increase in Parkinson's disease-related mortality among males in Northern Italy.
AB - BACKGROUND: According to standard mortality statistics based on the underlying
cause of death (UCOD), mortality from Parkinson's disease (PD) is increasing in
most European countries. However, mortality trends are better investigated taking
into account all the diseases reported in the death certificate (multiple causes
of death approach, MCOD). METHODS: All deaths of residents in the Veneto Region
(Northern Italy) aged>=45 years with any mention of PD were extracted from 2008
to 2015. The Annual Percent Change (APC) in age-standardized mortality rates was
computed both for PD as the UCOD, and by MCOD. The association with common
chronic comorbidities and acute complications was investigated by log-binomial
regression. The frequency of the mention of PD in death certificates was
investigated through linkage with an archive of patients with a previous clinical
diagnosis of the disease. RESULTS: PD was reported in 2.1% of all deaths, rising
from 1.9% in 2008 to 2.4% in 2015. Among males, age-standardized rates increased
over time both in analyses based on the UCOD (APC +4.1%; Confidence Interval
+1.5%,+6.7%), and on MCOD (APC +2.2%; +0.2,+4.2%). Among females time trends were
not significant. Mention of PD was associated with that of dementia/Alzheimer and
acute infectious diseases. Among known PD patients, the disease was reported only
in 60.2% of death certificates. CONCLUSIONS: Mortality associated to PD is
steeply increasing among males in Northern Italy; further investigations on time
trends for PD, both through all available electronic health archives and clinical
studies, should be set as a priority for epidemiological research.
PMID- 28416130
TI - pH-Dependant fluorescence switching of an i-motif structure incorporating an
isomeric azobenzene/pyrene fluorophore.
AB - In this study, we synthesized an Azo-py phosphoramidite, featuring azobenzene and
pyrene units, as a novel fluorescent and isomeric (trans- and cis-azobenzene
units) material, which we incorporated in an i-motif DNA sequence. We then
monitored the structural dynamics and changes in fluorescence as the modified DNA
sequences transformed from single strands at pH 7 to i-motif quadruplex
structures at pH 3. After incorporating Azo-py into the 4A loop position of an i
motif sequence, dramatic changes in fluorescence occurred as the DNA structures
changed from single-strands to i-motif quadruplex structures. Interestingly, the
cis form of Azo-py induced a more stable i-motif structure than did the trans
form, as confirmed from circular dichroism spectra and melting temperature data.
The absorption and fluorescence signals of these Azo-py-incorporated i-motif
systems exhibited switchable and highly correlated signaling patterns. Such
isomeric structures based on Azo-py might find potential applications in biology,
where control over stable i-motif quadruplex structures might be performed with
switchable fluorescence signaling.
PMID- 28416131
TI - Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C
allosteric NS5B RdRp inhibitor.
AB - Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central
role in virus replication. NS5B has no functional equivalent in mammalian cells,
and as a consequence is an attractive target for selective inhibition. This paper
describes the discovery of a novel family of HCV NS5B non-nucleoside inhibitors
inspired by the bioisosterism between sulfonamide and phosphonamide. Systematic
structural optimization in this new series led to the identification of IDX375, a
potent non-nucleoside inhibitor that is selective for genotypes 1a and 1b. The
structure and binding domain of IDX375 were confirmed by X-ray co-crystalisation
study.
PMID- 28416133
TI - Generation of a cysteine sulfinic acid analog for incorporation in peptides using
solid phase peptide synthesis.
AB - The sulfinic acid analog of aspartic acid, cysteine sulfinic acid, introduces a
sulfur atom that perturbs the acidity and oxidation properties of aspartic acid.
Cysteine sulfinic acids are often introduced in peptides and proteins by
oxidation of cysteine, but this method is limited as all cysteine residues are
oxidized and cysteine residues are often oxidized to sulfonic acids. To provide
the foundation for the specific incorporation of cysteine sulfinic acids in
peptides and proteins, we synthesized a 9-fluorenylmethyloxycarbonyl (Fmoc)
benzothiazole sulfone analog. Oxidation conditions to generate the sulfone were
examined and oxidation of the Fmoc-protected sulfide (3) with NbC in hydrogen
peroxide provided the corresponding sulfone (4) in the highest yield and purity.
Reduction with sodium borohydride generated the cysteine sulfinic acid (5)
suggesting this approach may be an efficient method to incorporate a cysteine
sulfinic acid in biomolecules. A model tripeptide bearing a cysteine sulfinic
acid was synthesized using this approach. Future studies are aimed at using this
method to incorporate cysteine sulfinic acids in peptide hormones and proteins
for use in the study of biological function.
PMID- 28416132
TI - Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential
treatments for hypertension.
AB - We report the discovery and hit-to-lead optimization of a structurally novel
indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series
displays potent inhibition of CYP11B2, high selectivity versus related steroidal
and hepatic CYP targets, and lead-like physical and pharmacokinetic properties.
On the basis of these and other data, the indazole series was progressed to lead
optimization for further refinement.
PMID- 28416134
TI - Syntheses of benzophenone-xanthone hybrid polyketides and their antibacterial
activities.
AB - Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca
longepedunculata. However, their biological activities have not been fully
investigated, since they are minor constituents in this plant. To evaluate the
possibility of muchimangins as antibacterial agent candidates, five muchimangin
analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the
corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the
Bronsted acid-catalysis. The antibacterial assays against Gram-positive bacteria,
Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria,
Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs
(+/-)-1,3,6,8-tetrahydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone
(1), (+/-)-1,3,6-trihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone
(2), and (+/-)-1,3-dihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)
xanthone (3) showed significant activities against S. aureus, with MIC values of
10.0, 10.0, and 25.0MUM, respectively. Analogs (+/-)-1 and (+/-)-2 also exhibited
antibacterial activities against B. subtilis, with MIC values of 50.0 and
12.5MUM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity
against S. aureus, with a MIC value of 10MUM.
PMID- 28416136
TI - Antipsychotics Use in Parkinson Disease: Separating Appropriate Therapies from
Treating Inappropriately.
PMID- 28416137
TI - Comment on "Preoperative asymmetry is a risk factor for reoperation in
involutional blepharoptosis".
PMID- 28416135
TI - All the "RAGE" in lung disease: The receptor for advanced glycation endproducts
(RAGE) is a major mediator of pulmonary inflammatory responses.
AB - The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory
pattern recognition receptor (PRR) that has been implicated in the pathogenesis
of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells
and was named for its ability to bind advanced glycation endproducts and promote
vascular inflammation in the vessels of patients with diabetes. Further studies
revealed that RAGE is most highly expressed in lung tissue and spurred numerous
explorations into RAGE's role in the lung. These studies have found that RAGE is
an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary
fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung
injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not
yet been targeted in the lungs of paediatric or adult clinical populations, but
the development of new ways to inhibit RAGE is setting the stage for the
emergence of novel therapeutic agents for patients suffering from these pulmonary
conditions.
PMID- 28416138
TI - Patient-centered outcomes of breast reconstruction in the setting of post
mastectomy radiotherapy: A comprehensive review of the literature.
AB - BACKGROUND: The impact of post-mastectomy radiotherapy (PMRT) on patient-centered
outcomes of breast reconstruction remains unclear. This comprehensive review aims
to consolidate the available data regarding aesthetic outcomes, patient
satisfaction, and the BREAST-Q(c) following breast reconstruction in the setting
of PMRT to facilitate the informed consent and shared decision-making process.
MATERIALS AND METHODS: A systematic search of the literature published from 2000
to 2016 in the PubMed/MEDLINE database was performed to identify all manuscripts
reporting aesthetic outcome, patient satisfaction, or BREAST-Q(c) scores of
patients undergoing PMRT and breast reconstruction. RESULTS: The initial search
identified 1604 potential titles. Ultimately, 29 manuscripts fit inclusion
criteria and were included in this review. A total of 21 studies reported
measures of aesthetic outcomes (1611 patients). Positive aesthetic outcomes
("good" or "better") widely varied in patients with prosthetic reconstruction and
ranged from 36% to 100%. In addition, positive aesthetic outcomes following
autologous reconstruction ranged from 70% to 90%. Measures of patient
satisfaction were evaluated in eight studies (722 patients). Satisfaction rates
ranged from 41% to 90% following prosthetic reconstruction and 74%-75% following
autologous reconstruction. BREAST-Q(c) findings were reported in four studies
(575 patients), all evaluating outcomes following prosthetic reconstruction. The
range of satisfaction with breasts was 48.9-57.2; satisfaction with outcome, 63.8
70.2; psychosocial well-being, 63.9-72.3; sexual well-being, 45.4-55.4; and
physical well-being, 71.7-75.1. CONCLUSIONS: Breast reconstruction in the setting
of PMRT is associated with poorer outcomes. However, the majority of studies
indicate that acceptable rates of positive aesthetic outcomes and patient
satisfaction can be achieved in the setting of PMRT.
PMID- 28416139
TI - CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond.
AB - Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide
T cells with engineered specificity. Clinical success in treating B-cell
malignancies has demonstrated the therapeutic potential of CAR-T cells against
cancer, and efforts are underway to expand the use of engineered T cells to the
treatment of diverse medical conditions, including infections and autoimmune
diseases. Here, we review current understanding of the molecular properties of
CARs, how this knowledge informs the rational design and characterization of
novel receptors, the successes and shortcomings of CAR-T cells in the clinic, and
emerging solutions for the continued improvement of CAR-T cell therapy.
PMID- 28416141
TI - Multiplexed Engineering and Analysis of Combinatorial Enhancer Activity in Single
Cells.
AB - The study of enhancers has been hampered by the scarcity of methods to
systematically quantify their endogenous activity. We develop Mosaic-seq to
systematically perturb enhancers and measure their endogenous activities at
single-cell resolution. Mosaic-seq uses a CRISPR barcoding system to jointly
measure a cell's transcriptome and its sgRNA modulators, thus quantifying the
effects of dCas9-KRAB-mediated enhancer repression in single cells. Applying
Mosaic-seq to 71 constituent enhancers from 15 super-enhancers, our analysis of
51,448 sgRNA-induced transcriptomes finds that only a small number of
constituents are major effectors of target gene expression. Binding of p300 and
RNAPII are key features of these constituents. We determine two key parameters of
enhancer activity in single cells: their penetrance in a population and their
contribution to expression in these cells. Through combinatorial interrogation,
we find that simultaneous repression of multiple weak constituents can alter
super-enhancer activity in a manner greatly exceeding repression of individual
constituents.
PMID- 28416142
TI - Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular
disease.
AB - Administration of drugs and other therapeutic agents has been the central
strategy of contemporary medicine for cardiovascular disease. The use of drug
delivery systems (DDS) includes micelles, liposomes, polymeric nanoparticles,
dendrimers, carbon nanotubes, and crystalline metals. Nano-DDS modify in vivo
drug kinetics, depending on (patho)physiological mechanisms such as retard
excretion, vascular permeability, and incorporation by mononuclear phagocyte
systems, which constitute the 'passive-targeting' property of nano-DDS. These
properties of nano-DDS are applicable to inflammatory diseases including
atherosclerosis. Atherosclerotic plaque destabilization and rupture account for
the majority of acute myocardial infarction, for which inflammatory monocytes and
macrophages play critical roles. In our experience, polymeric nanoparticles have
been delivered to inflammatory monocytes and macrophages in an atherosclerotic
mouse model. Nano-DDS loaded with pioglitazone reduced Ly6Chigh inflammatory
monocytes and increased Ly6Clow non-inflammatory monocytes in the peripheral
blood, and induced M2 macrophage-associated genes in the aorta. Pioglitazone
nanoparticles finally stabilized atherosclerotic plaques assessed by a decrease
in the number of buried fibrous caps in the plaque. Application of nano-DDS is a
unique and promising approach to prevent life-threatening cardiovascular events
including acute myocardial infarction by regulating inflammation in the
cardiovascular system.
PMID- 28416140
TI - Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA
Replication.
AB - Cells exposed to hypoxia experience replication stress but do not accumulate DNA
damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is
the only enzyme capable of de novo synthesis of deoxyribonucleotide triphosphates
(dNTPs). However, oxygen is an essential cofactor for mammalian RNR (RRM1/RRM2
and RRM1/RRM2B), leading us to question the source of dNTPs in hypoxia. Here, we
show that the RRM1/RRM2B enzyme is capable of retaining activity in hypoxia and
therefore is favored over RRM1/RRM2 in order to preserve ongoing replication and
avoid the accumulation of DNA damage. We found two distinct mechanisms by which
RRM2B maintains hypoxic activity and identified responsible residues in RRM2B.
The importance of RRM2B in the response to tumor hypoxia is further illustrated
by correlation of its expression with a hypoxic signature in patient samples and
its roles in tumor growth and radioresistance. Our data provide mechanistic
insight into RNR biology, highlighting RRM2B as a hypoxic-specific, anti-cancer
therapeutic target.
PMID- 28416143
TI - Changing the practice learning landscape.
AB - Engagement in real life practice has long been acknowledged as the most effective
way to learn a trade or profession and practice learning is consistently
highlighted by nursing and midwifery placement students for its impact on both
their professional and personal development. The paper examines the current
complexities of practice learning that have emerged from educational reform and
policy and debates the increased interest in the development of alternative
approaches to practice learning in the UK.
PMID- 28416144
TI - Feasibility of spirography features for objective assessment of motor function in
Parkinson's disease.
AB - OBJECTIVE: Parkinson's disease (PD) is currently incurable, however proper
treatment can ease the symptoms and significantly improve the quality of life of
patients. Since PD is a chronic disease, its efficient monitoring and management
is very important. The objective of this paper was to investigate the feasibility
of using the features and methodology of a spirography application, originally
designed to detect early Parkinson's disease (PD) motoric symptoms, for
automatically assessing motor symptoms of advanced PD patients experiencing motor
fluctuations. More specifically, the aim was to objectively assess motor symptoms
related to bradykinesias (slowness of movements occurring as a result of under
medication) and dyskinesias (involuntary movements occurring as a result of over
medication). MATERIALS AND METHODS: This work combined spirography data and
clinical assessments from a longitudinal clinical study in Sweden with the
features and pre-processing methodology of a Slovenian spirography application.
The study involved 65 advanced PD patients and over 30,000 spiral-drawing
measurements over the course of three years. Machine learning methods were used
to learn to predict the "cause" (bradykinesia or dyskinesia) of upper limb motor
dysfunctions as assessed by a clinician who observed animated spirals in a web
interface. The classification model was also tested for comprehensibility. For
this purpose a visualisation technique was used to present visual clues to
clinicians as to which parts of the spiral drawing (or its animation) are
important for the given classification. RESULTS: Using the machine learning
methods with feature descriptions and pre-processing from the Slovenian
application resulted in 86% classification accuracy and over 0.90 AUC. The
clinicians also rated the computer's visual explanations of its classifications
as at least meaningful if not necessarily helpful in over 90% of the cases.
CONCLUSIONS: The relatively high classification accuracy and AUC demonstrates the
usefulness of this approach for objective monitoring of PD patients. The positive
evaluation of computer's explanations suggests the potential use of this
methodology in a decision support setting.
PMID- 28416146
TI - Pseudomonas aeruginosa eradication: Finally moving the needle?
PMID- 28416145
TI - The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a
single and low dose of carbon tetrachloride in adult male rats.
AB - Gingko biloba leaves have been used as herbal medicine in China for 5000 years,
and the standardized leaf extract (GB-STE) has some beneficial effects in the
treatment of age-related, cardiovascular, and neurological diseases. The aim of
this study was to investigate the renoprotective effects of the Gingko biloba
extract (GbE) against the toxicity of a single and relatively low dose of carbon
tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux,
the concentration of total proteins in urine, the concentration of glucose in
urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as
two markers of renal function (clearance of inulin and p-aminohippurate); we also
compared the histological lesions caused by CCl4. Carbon tetrachloride increased
the urinary concentration of total proteins, and the renal concentration of MDA;
however, it did not modify the urine flux, urinary concentration of glucose, nor
the inuline or the p-aminohipurate clearances. Morphologically, CCl4 generated
some tubular damage that was more intense in the inner cortex of kidneys. The GbE
extract counteracted the effects of CCl4 on the concentration of total proteins
in urine, the concentration of renal MDA, and the renal histological changes. In
conclusion the main toxic effects produced by CCl4 were prevented by the GbE,
probably due to their antioxidant properties and the inhibition of the main P450
isoenzyme (CYP2E1) that metabolize CCl4.
PMID- 28416147
TI - Response to: Madelung deformity.
PMID- 28416148
TI - Alterations in autonomic cerebrovascular control after spinal cord injury.
AB - Among chronic cardiovascular and metabolic sequelae of spinal cord injury (SCI)
is an up-to four-fold increase in the risk of ischemic and hemorrhagic stroke,
suggesting that individuals with SCI cannot maintain stable cerebral perfusion.
In able-bodied individuals, the cerebral vasculature is able to regulate cerebral
perfusion in response to swings in arterial pressure (cerebral autoregulation),
blood gases (cerebral vasoreactivity), and neural metabolic demand (neurovascular
coupling). This ability depends, at least partly, on intact autonomic function,
but high thoracic and cervical spinal cord injuries result in disruption of
sympathetic and parasympathetic cerebrovascular control. In addition, alterations
in autonomic and/or vascular function secondary to paralysis and physical
inactivity can impact cerebrovascular function independent of the disruption of
autonomic control due to injury. Thus, it is conceivable that SCI results in
cerebrovascular dysfunction that may underlie an elevated risk of stroke in this
population, and that rehabilitation strategies targeting this dysfunction may
alleviate the long-term risk of adverse cerebrovascular events. However, despite
this potential direct link between SCI and the risk of stroke, studies exploring
this relationship are surprisingly scarce, and the few available studies provide
equivocal results. The focus of this review is to provide an integrated overview
of the available data on alterations in cerebral vascular function after SCI in
humans, and to provide suggestions for future research.
PMID- 28416149
TI - Escalated anthracycline dose in adult AML.
PMID- 28416150
TI - Stem cell transplantation in multiple myeloma.
PMID- 28416151
TI - American Association for Cancer Research Annual Meeting 2017.
PMID- 28416152
TI - Which size of amplatz sheath should be used for pediatric percutaneous
nephrolithotomy cases?
PMID- 28416153
TI - A critical review of patient safety indicators attributed to trauma surgeons.
AB - BACKGROUND: The Agency for Health Care Research and Quality (AHRQ) developed
patient safety indicators (PSIs) to identify events with a high likelihood of
representing medical error. The purpose of this study was to validate PSIs
attributed to trauma surgeons and compare validated PSIs to performance
improvement (PI) and morbidity and mortality (M&M) data. We hypothesized that
PSIs are not an indicator of quality of care in trauma. METHODS: PSI's attributed
to trauma surgeons (n=9) at our institution were reviewed (Jan-Dec 2015). An
initial review was conducted to ensure they met inclusion and exclusion criteria
(valid). "Valid" PSIs were distributed to the trauma division for secondary
review. RESULTS: 48 PSIs were identified (17.2 per 1000 cases) during the study
period. 19 were false positives yielding a positive predictive value of 60% (95%
CI 45-74%). False positive PSIs were the result of coding error (78%), present on
admission status (17%) and documentation error (5%). Valid PSIs (n=29) were
further analyzed. The most common were post-op PE/DVT (n=14), failure to rescue
(n=6) and accidental puncture/laceration (n=3). 60% of patients with a post-op
PE/DVT were started on chemoprophylaxis on admission and 40% had significant
intracranial hemorrhage; all were deemed non-preventable through trauma PI. All
deaths considered failure to rescue were classified as expected mortalities
during M&M review. Although not clinically significant, all cases of accidental
puncture/laceration (10% of valid PSIs) represented opportunities for
improvement. CONCLUSION: Overall, PSIs have low validity and do not reflect
quality of care in trauma.
PMID- 28416154
TI - A comparison of dicarbonyl stress and advanced glycation endproducts in lifelong
endurance athletes vs. sedentary controls.
AB - OBJECTIVES: Dicarbonyl stress and high concentrations of advanced glycation
endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD).
Exercise training lowers the risk for future CVD. We tested the hypothesis that
lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to
sedentary controls and that these differences relate to a better cardiovascular
health profile. DESIGN: Cross-sectional study. METHODS: We included 18 lifelong
endurance athletes (ATH, 61+/-7years) and 18 sedentary controls (SED, 58+/
7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3
deoxyglucosone (3DG) as markers of dicarbonyl stress. Furthermore, we measured
serum levels of protein-bound AGEs NE-(carboxymethyl)lysine (CML), NE
(carboxyethyl)lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and
pentosidine. Additionally, we measured cardiorespiratory fitness (VO2peak) and
cardiovascular health markers. RESULTS: ATH had lower concentrations of MGO (196
[180-246] vs. 242 [207-292] nmol/mmol lysine, p=0.043) and 3DG (927 [868-972] vs.
1061 [982-1114] nmol/mmol lysine, p<0.01), but no GO compared to SED. ATH
demonstrated higher concentrations CML and CEL compared to SED. Pentosidine did
not differ across groups and MG-H1 was significantly lower in ATH compared to
SED. Concentrations of MGO en 3DG were inversely correlated with cardiovascular
health markers, whereas CML and CEL were positively correlated with VO2peak and
cardiovascular health markers. CONCLUSION: Lifelong exercise training relates to
lower dicarbonyl stress (MGO and 3DG) and the AGE MG-H1. The underlying mechanism
and (clinical) relevance of higher CML and CEL concentrations among lifelong
athletes warrants future research, since it conflicts with the idea that higher
AGE concentrations relate to poor cardiovascular health outcomes.
PMID- 28416155
TI - Tracking of muscular strength and power from youth to young adulthood:
Longitudinal findings from the Childhood Determinants of Adult Health Study.
AB - OBJECTIVES: Low muscular fitness levels have previously been reported as an
independent risk factor for chronic disease outcomes. Muscular fitness tracking,
the ability to maintain levels measured at one point in time to another point in
time, was assessed from youth to adulthood to provide insight into whether early
identification of low muscular fitness in youth is possible. DESIGN: Prospective
longitudinal study. METHODS: Study including 623 participants who had muscular
fitness measures in 1985 (aged 9, 12 or 15 years) and again 20 years later in
young adulthood. Measures of muscular fitness were strength (right and left grip,
leg, shoulder extension and flexion measured by dynamometer, and a combined
strength score) and power (standing long jump distance). RESULTS: Strength and
power were relatively stable between youth and adulthood; the strongest tracking
correlations were observed for the combined strength score (r=0.47, p<=0.001),
right grip strength (r=0.43, p<=0.001) and standing long jump (r=0.43, p<=0.001).
Youth in the lowest third of muscular fitness had an increased risk of remaining
in the lowest third of muscular fitness in adulthood (strength: relative risk
(RR)=4.70, 95% confidence interval (CI) (3.19, 6.92); power: RR=4.06 (2.79,
5.90)). CONCLUSIONS: Youth with low muscular fitness are at increased risk of
maintaining a low muscular fitness level into adulthood. These findings warrant
investigation into the long term effects of early interventions that focus on
improving low muscular fitness levels in youth which could potentially improve
adult muscular fitness and reduce future chronic disease outcomes.
PMID- 28416156
TI - ?
PMID- 28416157
TI - Dentoskeletal sequellae after wearing of a mandibular advancement device in an
OSAHS setting.
AB - Mandibular advancement devices (MAD) are recommended in certain cases for the
treatment of obstructive sleep apnea and hypopnea syndrome (OSAHS). The aim of
this study was to make a retrospective investigation into the dental and skeletal
effects in patients suffering from OSAHS after wearing an MAD, and according to
the type of device, rigid or semi-rigid. Cephalometric criteria on lateral
cephalograms before and after at least 6 months of treatment were analyzed.
Twenty-two patients were included. We observed average labial tipping of the
lower incisors (+4.1+/-5.6 [P=0.0023]) and reduced overbite (-1.6+/-2.0mm
[P=0.0026]) and overjet (-1.4+/-2.3mm [P=0.0114]). Labial tipping of the
mandibular incisors was more pronounced with semi-rigid MAD. Similarly, the
decrease in overbite and overjet was more marked with the semi-rigid MAD. Medium
term wearing of MAD gives rise to dentally related occlusal changes, which can
only be corrected by orthodontic treatment.
PMID- 28416158
TI - ?
PMID- 28416159
TI - New finite element study protocol: Clinical simulation of orthodontic tooth
movement.
AB - The aim of this work was to model tooth movement in a more clinically-exact
fashion, thanks to the use of new IT tools and imaging systems (cone-beam). Image
segmentation and 3D reconstruction now enable us to model the anatomy
realistically, while finite element (FE) analysis makes it possible to evaluate
stresses and their distribution on the level of the tooth, the periodontal
ligament (PDL) and the alveolar bone when a force is applied. The principle is to
monitor tooth movement by obtaining optical impressions at each stage of
treatment. The model corresponds to a genuine clinical situation. FE analysis is
correlated with the clinically-observed displacement. The protocol remains long
and complex. It nevertheless makes it possible to obtain, throughout the duration
of treatment, patient-specific models that can be exploited using finite element
methods. It requires further validation in more thorough studies but offers
interesting prospects: precise study of induced tooth movement, distribution of
stresses in the PDL, and development of a customized previsualization tool.
PMID- 28416160
TI - The antidepressant-like effect of tDCS in mice: A behavioral and neurobiological
characterization.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive
method increasingly popular for the treatment of several brain disorders, such as
major depression. Despite great enthusiasm and promising results, some studies
report discrepant findings and no consensus exists for the clinical use of tDCS.
OBJECTIVE: The present study aims to (i) determine the most effective stimulation
parameters to optimize antidepressant-like effect of tDCS in the forced-swim test
in mice and (ii) identify brain regions recruited by tDCS and possibly involved
in its behavioral effect using Fos immunohistochemistry. RESULTS: We reported
that tDCS induced long-lasting antidepressant-like effect, which varied as a
function of stimulation settings including number, duration, intensity and
polarity of stimulation. Interestingly, the present study also demonstrated that
tDCS reduced depressive-like behaviors induced by chronic corticosterone
exposure. Furthermore, behavioral outcomes induced by a single stimulation were
associated with neuronal activation in the prefrontal cortex, dorsal hippocampus,
ventral tegmental area and nucleus accumbens, whereas no overexpression of c-fos
was associated with 10 stimulations. CONCLUSION: The strongest behavioral
response was observed with an anodal stimulation of 200 MUA during 20min. The
repetition of this stimulation was necessary to induce long-lasting behavioral
effects that are probably associated with plastic changes in the neuronal
response.
PMID- 28416161
TI - Cellular Senescence: A Translational Perspective.
AB - Cellular senescence entails essentially irreversible replicative arrest,
apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue
destructive senescence-associated secretory phenotype (SASP). Senescent cells
accumulate in various tissues with aging and at sites of pathogenesis in many
chronic diseases and conditions. The SASP can contribute to senescence-related
inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes,
chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent
cell accumulation or reducing senescent cell burden is associated with delay,
prevention, or alleviation of multiple senescence-associated conditions. We used
a hypothesis-driven approach to discover pro-survival Senescent Cell Anti
apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents,
drugs that cause senescent cells to become susceptible to their own pro-apoptotic
microenvironment. Several senolytic agents, which appear to alleviate multiple
senescence-related phenotypes in pre-clinical models, are beginning the process
of being translated into clinical interventions that could be transformative.
PMID- 28416162
TI - Pharmacokinetics of buprenorphine following constant rate infusion for
postoperative analgesia in dogs undergoing ovariectomy.
AB - OBJECTIVE: To investigate the pharmacokinetics of buprenorphine and its main
active metabolite, norbuprenorphine, after administration of an intravenous
loading dose followed by constant rate infusion (CRI) in dogs. STUDY DESIGN:
Prospective, clinical study. ANIMALS: A total of seven healthy dogs undergoing
elective ovariectomy. METHODS: Buprenorphine was administered as a loading dose
(intravenous bolus of 15 MUg kg-1) followed by CRI (2.5 MUg kg-1 hour-1 for 6
hours). Moreover, intraoperative analgesia was supplemented by an intramuscular
carprofen (4 mg kg-1) injection, administered prior to surgery, and by lidocaine,
administrated through subcutaneous infiltration and through a splash on the
ovarian vascular pedicle during surgery. Pain and sedation were scored for all
animals throughout the 24-hour study period and rescue analgesia was administered
when a visual analogue scale score was > 40 mm. Blood samples were collected from
a jugular catheter at regular intervals, and plasma concentrations of
buprenorphine and norbuprenorphine were determined by a validated liquid
chromatography-tandem mass spectrometry method. RESULTS: Buprenorphine showed a
two-compartment kinetic profile. Maximum concentration was 23.92 +/- 8.64 ng mL-1
at 1 minute (maximum time); elimination half-life was 41.87 +/- 17.35 minutes;
area under the curve was 486.68 +/- 125.66 minutes ng-1 mL-1; clearance was 33.61
+/- 13.01 mL minute-1 kg-1, and volume of distribution at steady state was 1.77
+/- 0.50 L kg-1. In no case was rescue analgesia required. Norbuprenorphine
resulted below the lower limit of quantification in almost all samples.
CONCLUSIONS AND CLINICAL RELEVANCE: The results suggest that a buprenorphine CRI
can be a useful tool for providing analgesia in postoperative patients,
considering its minor side effects and the advantages of a CRI compared to
frequent boluses. The negligible contribution of norbuprenorphine to the
therapeutic effect was confirmed.
PMID- 28416163
TI - Nanosheets for Delivery of Biomolecules into Plant Cells.
AB - Layered double hydroxides (LDHs) are sheet-formed nanoparticles (NPs) of
adjustable size. It has recently been reported that LDHs have the ability to
deliver biomolecules into intact plant cells. LDHs show promise as a novel and
powerful tool for plant cell studies and similar applications.
PMID- 28416164
TI - Morphological variability of the earlobe in a Spanish population sample.
AB - This article shows the morphological variability of the earlobe in a Spanish
population of European origin. The frequencies of four lobe characteristics
(attachment, contour, modeling, and size) and their degree of expression were
studied. The relationship among the characteristics and the differences involving
sex and laterality were also considered. The least frequent morphology, and of
main use in solving forensic cases, was the very small size with triangle-pulled
contour into the skin and crossed-discontinuous modeling. The most frequent
morphology, and most clinically useful, was the medium-sized lobe with free
arched contour and eminent or cross-continuous modeling. The characteristics were
all symmetric. Size and modeling showed sexual dimorphism. Some characteristics
were associated with each other: attachment with contour and modeling and the
contour with modeling and size. The least frequent peculiarities were sharp lobe
and virgule. The literature is scarce on this matter, practically non-existent
for some characteristics, especially modeling and peculiarities. For the first
time, the associations of the ear characteristics were analyzed, and this
information could be applied to forensic identification.
PMID- 28416165
TI - Influence of Cardiovascular Risk in the Prediction and Timing of Cardiac Events
After Exercise Echocardiogram Testing Without Ischemia.
AB - INTRODUCTION AND OBJECTIVES: There have been no analyses of the influence of
cardiovascular risk as a predictor of events in patients with exercise
echocardiography (EE) without ischemia. Our objective was to determine the
predictors of cardiac events, paying special attention to cardiovascular risk.
METHODS: This study included 1640 patients with EE without ischemia. Of these,
there were 1206 with no previously known coronary artery disease (CAD), whose
risk of a fatal cardiovascular disease event was estimated according to the
European SCORE (Systematic COronary Risk Evaluation) risk assessment system, and
434 with known CAD. The primary endpoint was cardiac event-free survival (EFS)
(cardiac death, nonfatal acute coronary syndrome, and coronary
revascularization). RESULTS: After a median follow-up of 35 [23-54] months, no
differences were found in cardiac EFS between patients with a SCORE >= 10 or
diabetes and patients with previous CAD (89.8% vs 87.1%). In the first year,
cardiac EFS was high in all groups (99.4% if SCORE < 5; 100% if 5-9; 98% if >= 10
or diabetes and 97% in patients with CAD). In the third year, cardiac EFS was
similar in the group with SCORE >= 10 or diabetes (94.5%) and patients with CAD
(91.1%, P = NS). In these patients, the annualized event rate was 2.8% and 2.55%,
respectively, and was significantly higher than in groups with SCORE < 5 (0.6%)
and SCORE 5-9 (0.12%). The most frequent events were non-ST-segment elevation
acute coronary syndrome and late revascularization. Predictors of cardiac events
were previous CAD, SCORE >= 10 or diabetes mellitus, creatinine clearance, left
ventricular ejection fraction, and chest pain during EE. CONCLUSIONS: Initial
outcome after an EE without ischemia is favorable but is subsequently modulated
by cardiovascular risk.
PMID- 28416166
TI - Two-year outcomes of balloon-occluded retrograde transvenous obliteration of
gastric varices in liver transplant recipients: A multi-institutional study.
AB - PURPOSE: To assess the 2-year effectiveness and safety of balloon-occluded
retrograde transvenous obliteration (BRTO) for gastric varices (GVs) in liver
transplant recipients. MATERIALS AND METHODS: Eleven liver transplant recipients
underwent consecutive BRTO for GVs at four institutions. Patients included eight
(73%) men and three (27%) women with mean age of 56 years+/-12 (SD) (range: 26-67
years). Underlying cause of liver transplantation was hepatitis C virus (HCV)
related cirrhosis in five (45%), alcohol- and HCV-related cirrhosis in three
(27%), primary biliary cirrhosis in two (18%), and alcoholic cirrhosis in one
(9%). Five (45%) patients underwent BRTO for actively bleeding GVs, three (17%)
for high-risk GVs, and three (17%) for augmentation of portal venous flow through
obliteration of gastrorenal shunts. Mean time between liver transplantation and
BRTO was 78 months (range: 0.1-276 months). Technical success, GVs obliterative
rates, and immediate complications were recorded. Post-BRTO hemorrhagic,
transplant, and overall survival rates were evaluated at 6, 12, and 24 months.
RESULTS: All (100%) procedures were technically successful. Complete GVs
obliteration was achieved in ten patients (91%). Two major complications (18%)
occurred in the immediate post-procedure period. One patient developed complete
portal vein thrombosis, and another patient developed consumptive coagulopathy,
ultimately leading to death. No post-BRTO hemorrhagic recurrences were seen at 6,
12, or 24 months. One patient (9%) had delayed upper gastrointestinal bleeding at
34 months after the procedure which was managed conservatively. Transplant and
overall survival rates were 91% at 6, 12, and 24 months. CONCLUSION: BRTO has
high technical success and complete GVs obliterative rates in liver transplant
recipients with few complications and high graft survival rates.
PMID- 28416167
TI - Partial reinforcement of avoidance and resistance to extinction in humans.
AB - In anxiety, maladaptive avoidance behavior provides for near-perfect
controllability of potential threat. There has been little laboratory-based
treatment research conducted on controllability as a contributing factor in the
transition from adaptive to maladaptive avoidance. Here, we investigated for the
first time whether partial reinforcement rate, or the reliability of avoidance at
controlling or preventing contact with an aversive event, influences subsequent
extinction of avoidance in humans. Five groups of participants were exposed to
different partial reinforcement rates where avoidance cancelled upcoming shock on
100%, 75%, 50%, 25% or 0% of trials. During extinction, all shocks were withheld.
Avoidance behavior, online shock expectancy ratings and skin conductance
responses (SCRs) were measured throughout. We found that avoidance was a function
of relative controllability: higher reinforcement rate groups engaged in
significantly more extinction-resistant avoidance than lower reinforcement
groups, and shock expectancy was inversely related with reinforcement rate during
avoidance acquisition. Partial reinforcement effects were not evident in SCRs.
Overall, the current study highlights the clinical relevance of laboratory-based
treatment research on partial reinforcement or controllability effects on
extinction of avoidance.
PMID- 28416168
TI - Non-invasive preimplantation genetic screening using array comparative genomic
hybridization on spent culture media: a proof-of-concept pilot study.
AB - The aim of this pilot study was to assess if array comparative genomic
hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on
blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on
22 spent blastocyst culture media samples after polar body PGS because of
advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm
injection and all embryos underwent assisted hatching. Concordance of polar body
analysis and culture media genetic results was assessed. Thirteen out of 18
samples (72.2%) revealed general concordance of ploidy status (euploid or
aneuploid). At least one chromosomal aberration was found concordant in 10 out of
15 embryos found to be aneuploid by both polar body and culture media analysis.
Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant
between the culture media and polar body analysis. By analysing negative controls
(oocytes with fertilization failure), notable maternal contamination was
observed. Therefore, non-invasive PGS could serve as a second matrix after polar
body or cleavage stage PGS; however, in euploid results, maternal contamination
needs to be considered and results interpreted with caution.
PMID- 28416169
TI - Pathologic fracture of the thoracic spine in a male master ultra-marathoner due
to the combination of a vertebral hemangioma and osteopenia.
AB - Vertebral hemangiomas are the most common benign vertebral neoplasms and are
generally asymptomatic. In the present study, we report the case of a 52-year-old
male master ultra-marathoner suffering from a pathologic fracture of the thoracic
spine due to a vertebral hemangioma. A further examination in the athlete
revealed an accompanying osteopenia, which was most likely due to a deficiency in
both vitamin D and testosterone. The treatment of the fracture consisted of
percutaneous vertebroplasty. Shortly after the operation the athlete was able to
continue running. The most likely reason for the pathologic fracture of the
vertebral body was the combination of the vertebral hemangioma and osteopenia.
The further treatment consisted of supplementation of both vitamin D and
testosterone. Athletes and physicians should be aware that male master ultra
marathoners older than 50 years might suffer from osteopenia, where a deficiency
in vitamin D and testosterone could be contributing factors for osteopenia
development in general.
PMID- 28416170
TI - Hepcidin serum levels and resistance to recombinant human erythropoietin therapy
in hemodialysis patients.
AB - OBJECTIVE: The aim of this study was to analyze the factors that are associated
with the response to erythropoiesis-stimulating agents (ESAs) and its association
with hospitalization and mortality rates; to evaluate the serum hepcidin level
and its associations with iron profile, inflammatory markers, ESA responsiveness,
and mortality; and to determine independent factors affecting ERI and hepcidin.
MATERIALS AND METHODS: To evaluate a dose-response effect of ESAs we used the
erythropoietin resistance index (ERI). Patients were stratified in two groups:
nonresponders and responders (ERI>15, n=20, and ERI <=15U/kg/week/g per 100mL,
n=153, respectively). Hematological data, hepcidin levels, iron parameters,
inflammatory markers, hospitalization and mortality rates were compared between
the groups. Multiple regression analysis was used to determine independent
factors affecting ERI and hepcidin. RESULTS: C-reactive protein (CRP)
(beta=0.078, P=0.007), albumin (beta=-0.436, P=0.004), body mass index (beta=
0.374, P<0.001), and hospitalization rate per year (beta=3.017, P<0.001) were
found to be significant determinants of ERI in maintenance hemodialysis (MHD)
patients. Inadequate dialysis was associated with higher ERI. Patients with
concomitant oncological diseases had higher ERI (31.2+/-12.4 vs 9.7+/
8.1U/kg/week/g per 100mL, P=0.002). The hepcidin level was 158.51+/-162.57 and
120.65+/-67.28ng/mL in nonresponders and responders, respectively (P=0.33).
Hepcidin correlated directly with ERI, dose of ESAs, ferritin and inversely with
Hb, transferrin saturation, and albumin. ERI (beta=4.869, P=0.002) and ferritin
(beta=0.242, P=0.003) were found to be significant determinants of hepcidin in
MHD patients. The hospitalization rate per year was 2.35+/-1.8 and 1.04+/-1.04 in
nonresponders and responders, respectively (P=0.011). The mean length of one
hospitalization was 25.12+/-21.26 and 10.82+/-17.25 days, respectively (P=0.012).
Death occurred in 30% of the patients from the responders' group and in 50% from
the nonresponders' group (P=0.289). The mean hepcidin concentration of patients
who died was 141.9+/-129.62ng/mL and who survived, 132.98+/-109.27ng/mL
(P=0.797). CONCLUSIONS: CRP, albumin, BMI, and hospitalization rate per year were
found to be significant determinants of ERI in MHD patients. Inadequate dialysis
was associated with higher epoetin requirements. There were no difference in
patient mortality by ERI, but a significant difference in hospitalization rates
and mean length of one hospitalization was revealed. A significant positive
relation between hepcidin and ERI was revealed. ERI and ferritin were found to be
significant determinants of hepcidin in MHD patients. Hepcidin was not related to
mortality.
PMID- 28416171
TI - The comparison of knee osteoarthritis treatment with single-dose bone marrow
derived mononuclear cells vs. hyaluronic acid injections.
AB - OBJECTIVE: The aim of this study was to compare treatment methods of the knee
joint degenerative osteoarthritis, using autologous bone marrow-derived
mononuclear cells and hyaluronic acid injections and observe prevalence of
adverse effects in both groups. MATERIALS AND METHODS: A prospective randomized
controlled clinical trial was carried out. The analysis of pain and changes in
osteoarthritis symptoms after a single intra-articular bone marrow-derived
mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II
III osteoarthritis during the 12-month period were performed. The results were
compared with the control group treated routinely by hyaluronic acid injections
therapy. A therapy group of patients (n=28) received single bone marrow-derived
mononuclear cell intra-articular injections. A control group of patients (n=28)
was treated with a total of three sodium hyaluronate intra-articular injections
each one performed a week apart. The clinical results were obtained using the
Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before
and 3, 6, and 12 months after injection. RESULTS: A statistically significant
improvement was observed in the mononuclear cell group over the starting point in
all scores. At the endpoint at month 12, the KOOS score improved significantly
(P<0.05) on the pain subscale (+25.44), activity and daily living subscale
(+21.36), quality of life subscale (+28.83), and total KOOS (+18.25). The KSS
score also demonstrated a significant improvement on the symptoms subscale
(+25.42) and the function subscale (+38.32) (P<0.001). The KOOS symptoms and
sports subscales improved without statistical significance. The difference
between the control group treated with hyaluronic acid versus the bone marrow
derived mononuclear cells group at time points 6 and 12 months demonstrated a
statistically significant (P<0.05) superiority in the KOOS pain subscale over the
hyaluronic acid group. In both groups serious adverse effects were not observed.
CONCLUSIONS: The intra-articular injection of bone marrow-derived mononuclear
cells is a safe manipulation with no side effects during the 12-month period.
This treatment provides statistically significant clinical improvement between
the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic
acid treatment, better pain relief in the long-term period of mononuclear cell
group was observed.
PMID- 28416172
TI - Epidemiology of ebolavirus disease (EVD) and occupational EVD in health care
workers in Sub-Saharan Africa: Need for strengthened public health preparedness.
AB - Ebolavirus disease (EVD) is a severe contagious disease in humans, and health
care workers (HCW) are at risk of infection when caring for EVD patients. This
paper highlights the epidemiologic profile of EVD and its impact on the health
care workforce in Africa. A documentary study was conducted which consisted of a
review of available literature regarding the epidemiology of EVD, occupational
EVD (OEVD), and work safety issues in Sub-Saharan Africa; the literature findings
are enriched by field experiences from the authors. EVD outbreaks have already
caused 30,500 cases in humans of whom 12,933 died (as of September 9, 2015), and
the number of infected HCW has dramatically increased. All eight HCW infected
during the 2014 outbreak in Democratic Republic of the Congo died, whereas during
the recent West African EVD epidemic more than 890 HCW were infected, with a case
fatality rate of 57%. Occupational exposure to blood and other body fluids due to
inadequate use of personal protective equipment and needle stick or sharp
injuries are among factors that contribute to the occurrence of OEVD. Prevention
of OEVD should be one of the top priorities in EVD outbreak preparedness and
management, and research should be conducted to elucidate occupational and other
factors that expose HCW to EVD. In addition to regularly training HCW to be
adequately prepared to care for patients with EVD, it is critical to strengthen
the general health care system and improve occupational safety in medical
settings of countries at risk.
PMID- 28416173
TI - [Cardiac arrest animal model: a simple device for small animals' chest
compression].
PMID- 28416174
TI - [Ultrasound guided quadratus lumborum block for analgesia after cesarean
delivery: case series].
AB - INTRODUCTION: The majority of women having planned cesarean section receive
spinal anesthesia for the procedure. Typically, spinal opioids are administered
during the same time as a component of multimodal analgesia to provide pain
relief in the 16-24h period postoperatively. The quadratus lumborum block is a
regional analgesic technique that blocks T5-L1 nerve branches and has an evolving
role in postoperative analgesia for lower abdominal surgeries and may be a
potential alternative to spinal opioids. If found effective, it will have the
advantage of a reduction in opioid associated adverse effects while providing
similar quality of analgesia. METHODS: We performed bilateral quadratus lumborum
block in 3 women who received a spinal anesthetic for a cesarean delivery and
evaluated their post-operative opioid consumption and patient satisfaction.
RESULTS: In all 3 patients, there was no additional opioid consumption during the
first 24h after the block. Numeric Rating Scale (NRS) for pain was less than 6
for the first 24h. Women were all very satisfied with the quality of pain relief.
DISCUSSION: Quadratus lumborum block may be a promising anesthetic adjuvant for
post-cesarean analgesia. Further randomized controlled trials are needed to
compare the efficacy of the quadratus lumborum block with intrathecal opioids.
PMID- 28416175
TI - Corneal Endothelial Cell Density in Children: Normative Data From Birth to 5
Years Old.
PMID- 28416176
TI - Maternal early warning systems-Towards reducing preventable maternal mortality
and severe maternal morbidity through improved clinical surveillance and
responsiveness.
AB - Despite increasing awareness of obstetric safety initiatives, maternal mortality
and severe maternal morbidity in the United States have continued to increase
over the past 20 years. Since results from large-scale surveillance programs
suggest that up to 50% of maternal deaths may be preventable, new efforts are
focused on developing and testing early warning systems for the obstetric
population. Early warning systems are a set of specific clinical signs or
symptoms that trigger the awareness of risk and an urgent patient evaluation,
with the goal of reducing severe morbidity and mortality through timely diagnosis
and treatment. Early warning systems have proven effective at predicting and
reducing mortality and severe morbidity in medical, surgical, and critical care
patient populations; however, there has been limited research on how to adapt
these tools for use in the obstetric population, where physiologic changes of
pregnancy render them inadequate. In this article, we review the available
obstetric early warning systems and present evidence for their use in reducing
maternal mortality and severe maternal morbidity. We also discuss considerations
and strategies for implementation and acceptance of these early warning systems
for clinical use in obstetrics.
PMID- 28416177
TI - Restoring: How older adults manage their recovery from hip fracture.
AB - AIMS AND OBJECTIVES: To generate a substantive theory that explained recovery
from hip fracture from the perspective of older adults and find out how they
managed it. BACKGROUND: Hip fracture is a well-researched phenomenon. The
perspective of how older adults recover from hip fracture has been examined least
of all. Patients spend less time in hospital following injury and generally
recover in their home setting. DESIGN: A Glaserian grounded theory approach was
used for this study. METHODS: Semi-structured interviews (n-21) were conducted
with older adult's post discharge following hip fracture. Data were collected,
analysed and theorised using the grounded theory methodology. RESULTS: Older
adults recovering from hip fracture were restored back to normal through a
process in which they continuously balanced regaining of physical and social
functioning against reasserting usual psycho-social behaviours within different
contexts. Importantly, the older adult's personal recovery process starts within
the acute setting once the person regains physical functioning, especially
regaining mobility. From this point onwards, older adults will respond to health
professionals, instructions and interventions in many ways. The responses will be
based on their developmental life stage to enable them to counter the diverse
expectations placed on them by health professionals, social networks and their
self-beliefs. CONCLUSION: Nurses need to understand that older adults will
recover in their own way following discharge, often re-interpreting health
information to fit their own situations.
PMID- 28416178
TI - The effect of time to surgery on functional ability at six weeks in a hip
fracture population in Mid-West Ireland.
AB - Patients with a hip fracture may be appropriately delayed for surgery as they
require optimisation or clinical interventions to treat acute medical illnesses
(Moja et al., 2012). Other patients are inappropriately delayed due to hospital
factors (Brener, 2013; Lee & Elfar, 2014). Timely efficient admission and surgery
is well documented as the best course of management for these patients. The aim
of this prospective cohort longitudinal follow-up study was to establish if a
relationship existed between duration of time spent in the Emergency Department
(ED), time to surgery and functional ability in patients with hip fractures and
to examine the effect prolonged waits may have on ability to return home.
Functional ability for fifty one patients with a hip fracture was evaluated using
the Barthel Index Score (BIS) on admission and at six weeks post-surgery. Data
were analysed by using SPSS version 20. The findings reveal a change in BIS at 6
weeks for patients whose surgery is delayed. Patients who experienced long delays
awaiting admission (>12 h) in the ED functioned less well (Kruskal-Wallis test p
= 0.033). Correlation existed between time to surgery and returning to pre
fracture place of residence, (p = 0.000 Pearson chi-square), which also remained
significant while controlling for age. Prolonged waits had an overall negative
impact on patients' post-fracture functional ability. This study highlights the
deleterious effects on functional ability when surgery is delayed.
PMID- 28416179
TI - Increased risk of ventral hernia recurrence after pregnancy: A nationwide
register-based study.
AB - BACKGROUND: Female patients of reproductive age constitute a substantial portion
of patients undergoing ventral hernia repair, however the impact of pregnancy on
the risk of recurrence is scarcely documented. The aim of the study was to
evaluate if pregnancy following ventral hernia repair was associated with an
increased risk of recurrence. METHODS: This nationwide cohort study included all
female patients of reproductive age registered in the Danish Ventral Hernia
Database with ventral hernia repair between 2007 and 2013. The primary outcome
was ventral hernia recurrence. Multivariable extended Cox regression analysis was
performed. RESULTS: A total of 3578 patients were included in the study, 267
(7.5%) of whom subsequently became pregnant during follow-up. The median follow
up was 3.1 years (range 0-8.4 years). Pregnancy was independently associated with
recurrence (hazard ratio 1.56, 95% confidence interval 1.09-2.25, P = 0.016).
CONCLUSIONS: Pregnancy after ventral hernia repair was independently associated
with ventral hernia recurrence.
PMID- 28416180
TI - Revision of sleeve gastrectomy to Roux-en-Y Gastric Bypass: A Canadian
experience.
AB - INTRODUCTION: Sleeve gastrectomy (SG) can be associated with inadequate weight
loss, insufficient resolution of co-morbidities and severe reflux. Conversion to
Roux-en-Y Gastric Bypass (RYGB) is a potential solution. The aim of this study
was to determine the common indications for conversion from SG to RYGB at our
centre, and evaluate patient outcomes with respect to weight loss and co
morbidity resolution. METHODS: A retrospective review of patients who underwent
conversion from SG to RYGB between 2008 and 2015. RESULTS: 273 SGs were performed
of which 6.6% (n = 18) were converted to RYGB most commonly due to inadequate
weight loss (65.3%) and severe reflux (26.1%). Two patients were converted as a
planned two-stage approach to RYGB. Patients went from a mean preoperative BMI of
50.5 to a mean BMI of 40.5 post-SG on average by 20.9 months. The mean time to
conversion was 41.8 months. There was a positive correlation between pre-SG BMI
and time to conversion (p = 0.040). The mean BMI after conversion was 36.4, but
this additional weight loss was not significant (p = 0.057). After conversion,
four of the five diabetic patients are now medication free and 75% of patients no
longer have reflux symptoms. All patients had complete resolution of their
hypertension and obstructive sleep apnea. Revision perioperative complication
rates were comparable to primary RYGB. Two patients developed new onset iron
deficiency anemia. CONCLUSION: Revision to RYGB is a safe option for SG failure
and resulted in significant benefits from co-morbidity resolution.
PMID- 28416181
TI - A comparison of a novel robust decentralised control strategy and MPC for
industrial high purity, high recovery, multicomponent distillation.
AB - In this work we have developed a novel, robust practical control structure to
regulate an industrial methanol distillation column. This proposed control scheme
is based on a override control framework and can manage a non-key trace ethanol
product impurity specification while maintaining high product recovery. For
comparison purposes, a MPC with a discrete process model (based on step tests)
was also developed and tested. The results from process disturbance testing shows
that, both the MPC and the proposed controller were capable of maintaining both
the trace level ethanol specification in the distillate (XD) and high product
recovery (beta). Closer analysis revealed that the MPC controller has a tighter
XD control, while the proposed controller was tighter in beta control. The tight
XD control allowed the MPC to operate at a higher XD set point (closer to the
10ppm AA grade methanol standard), allowing for savings in energy usage. Despite
the energy savings of the MPC, the proposed control scheme has lower installation
and running costs. An economic analysis revealed a multitude of other external
economic and plant design factors, that should be considered when making a
decision between the two controllers. In general, we found relatively high energy
costs favour MPC.
PMID- 28416182
TI - Dynamical tuning for MPC using population games: A water supply network
application.
AB - Model predictive control (MPC) is a suitable strategy for the control of large
scale systems that have multiple design requirements, e.g., multiple physical and
operational constraints. Besides, an MPC controller is able to deal with multiple
control objectives considering them within the cost function, which implies to
determine a proper prioritization for each of the objectives. Furthermore, when
the system has time-varying parameters and/or disturbances, the appropriate
prioritization might vary along the time as well. This situation leads to the
need of a dynamical tuning methodology. This paper addresses the dynamical tuning
issue by using evolutionary game theory. The advantages of the proposed method
are highlighted and tested over a large-scale water supply network with periodic
time-varying disturbances. Finally, results are analyzed with respect to a multi
objective MPC controller that uses static tuning.
PMID- 28416183
TI - Inhibition of the in vitro growth of Babesia bigemina, Babesia caballi and
Theileria equi parasites by trifluralin analogues.
AB - Bovine and equine babesiosis caused by Babesia bovis, Babesia bigemina and
Babesia caballi, along with equine theileriosis caused by Theileria equi are
global tick-borne hemoprotozoan diseases characterized by fever, anemia, weight
losses and abortions. A common feature of these diseases are transition from
acute to chronic phases, in which parasites may persist in the hosts for life.
Antiprotozoal drugs are important for managing infection and disease. Previous
research demonstrated that trifluralin analogues, designated (TFLAs) 1-15, which
specifically bind to regions of alpha-tubulin protein in plants and protozoan
parasites, have the ability to inhibit the in vitro growth of B. bovis. The
inhibitory activity of TFLAs 1-15 minus TFLA 5 was tested in vitro against
cultured B. bigemina, B. caballi and T. equi. The four TFLAs with greatest
inhibitory activity were then analyzed for hemolytic activity and toxicity
against erythrocytes. All TFLAs tested in the study showed inhibitory effects
against the three parasite species. TFLA 2, TFLA 11, TFLA 13 and TFLA 14 were the
most effective inhibitors for the three species tested, with estimated IC50
between 5.1 and 10.1MUM at 72h. The drug's solvent (DMSO/ethanol) did not
statistically affect the growth of the parasites nor cause hemolysis. Also, TFLA
2, 13 and 14 did not cause statistically significant hemolytic activity on bovine
and equine erythrocytes at 15MUM, and TFLA 2, 11 and 13 had no detectable toxic
effects on bovine and equine erythrocytes at 15MUM, suggesting that these drugs
do not compromise erythrocyte viability. The demonstrated ability of the
trifluralin analogues to inhibit in vitro growth of Babesia spp. and Theileria
equi, and their lack of toxic effects on erythrocytes supports further in vivo
testing and eventually their development as novel alternatives for the treatment
of babesiosis and theileriosis.
PMID- 28416185
TI - American Society for Metabolic and Bariatric Surgery position statement on the
impact of obesity and obesity treatment on fertility and fertility therapy
Endorsed by the American College of Obstetricians and Gynecologists and the
Obesity Society.
PMID- 28416186
TI - Nutritional deficiencies four years after laparoscopic sleeve gastrectomy-are
supplements required for a lifetime?
AB - BACKGROUND: Data regarding long-term nutritional deficiencies following
laparoscopic sleeve gastrectomy (LSG) are scarce. OBJECTIVES: To assess the
prevalence of nutritional deficiencies and supplement consumption 4 years post
LSG. SETTING: Hebrew University, Israel. METHODS: Data were collected
prospectively from preoperative and 1 and 4 years postoperative including
anthropometric parameters, biochemical tests, and supplement intake. RESULTS:
Data were available for 192, 77, and 27 patients at presurgery and 1 and 4 years
post-LSG, respectively. Prevalence of nutritional deficiencies at baseline and 1
and 4 years postsurgery, respectively, were specifically for iron (44%, 41.2%,
28.6%), anemia (11.5%, 20%, 18.5%), folate (46%, 14.3%, 12.5%), vitamin B12
(7.7%, 13.6%, 15.4%), vitamin D (96.2%, 89%, 86%), and elevated parathyroid
hormone (PTH) (52%, 15.4%, 60%). Vitamin D levels remained low throughout the
whole period. PTH levels were 37.5 pg/mL at 1 year postsurgery and increased to
77.3 pg/mL at 4 years postsurgery (P = .009). Females had higher prevalence of
elevated PTH and a tendency for higher rates of anemia, compared with males 4
years postsurgery (80% versus 20%, P = .025; and 28% versus 0%, P = .08,
respectively). Of the patients, 92.6% reported taking a multivitamin and 74.1%
vitamin D supplements during the first postoperative year, while after 4 years
only 37% and 11.1% were still taking these supplements, respectively. CONCLUSION:
A high rate of nutritional deficiencies is common at 4 years post-LSG along with
low adherence to the nutritional supplementation regimen. Long-term nutritional
follow-up and supplementation maintenance are crucial for LSG patients. Future
studies are needed to clarify the clinical impact of such deficiencies.
PMID- 28416184
TI - TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in
the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.
AB - Aberrant WNT signaling drives colorectal cancer (CRC). Here, we identify TIAM1 as
a critical antagonist of CRC progression through inhibiting TAZ and YAP,
effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the
cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two
compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and
promotes TAZ degradation by enhancing its interaction with betaTrCP. Nuclear
TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP
target genes implicated in epithelial-mesenchymal transition, cell migration, and
invasion, and consequently suppresses CRC cell migration and invasion.
Importantly, high nuclear TIAM1 in clinical specimens associates with increased
CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses
tumor progression by regulating YAP/TAZ activity.
PMID- 28416187
TI - Comment: Value of routine upper gastrointestinal swallow study after laparoscopic
sleeve gastrectomy.
PMID- 28416188
TI - A giraffe neck sign of the medial meniscus: A characteristic finding of the
medial meniscus posterior root tear on magnetic resonance imaging.
AB - BACKGROUND: The posterior root ligament of the medial meniscus (MM) has a
critical role in regulating the MM movement. An accurate diagnosis of the MM
posterior root tear (MMPRT) using magnetic resonance imaging (MRI) is important
for preventing sequential osteoarthritis following the MMPRT. However, diagnosis
of the MMPRT is relatively difficult even after using several characteristic MRI
findings. The aim of this study was to identify a useful meniscal body sign of
the MMPRT for improving diagnostic MRI reading. METHODS: Eighty-five patients who
underwent surgical treatments for the MMPRT (39 knees) and other types of MM
tears (49 knees) were included. The presence of characteristic MRI findings such
as cleft sign, ghost sign, radial tear sign, medial extrusion sign, and new
meniscal body shape-oriented "giraffe neck sign" was evaluated in 120 MRI
examinations. RESULTS: Giraffe neck signs were observed in 81.7% of the MMPRTs
and in 3.3% of other MM tears. Cleft, ghost, and radial tear signs were highly
positive in the MMPRTs compared with other MM tears. Medial extrusion signs were
frequently observed in both groups. Coexistence rates of any 2 MRI signs, except
for medial extrusion sign, were 91.7% in the MMPRT group and 5% in other MM
tears. CONCLUSIONS: This study demonstrated that a new characteristic MRI finding
"giraffe neck sign" was observed in 81.7% of the MMPRT. Our results suggest that
the combination of giraffe neck, cleft, ghost, and radial tear signs may be
important for an accurate diagnostic MRI reading of the MMPRT.
PMID- 28416189
TI - The validity and reliability of the Arabic version of the Japanese Orthopedic
Association Back Pain Evaluation Questionnaire: Can we implement it in Saudi
Arabia?
AB - BACKGROUND: The Japanese Orthopedic Association designed their back pain
evaluation questionnaire (JOABPEQ) which was proven to be feasible, reliable and
valid. The questionnaire's validity and reliability were confirmed when it was
implemented in patients with different cultural background. Since the JOABPEQ
still has not been utilized in any of the Arabic countries, we present the Arabic
version with its validity and reliability. METHODS: After ensuring an optimal
forward-backward translation of the JOABPEQ, the Arabic version was distributed
among 151 patients visiting our clinics from December 2015 to February 2016. The
reliability was tested using Cronbach's alpha. The convergent validity was
assessed through aggregating and correlating the questionnaire's items with their
previously designed and validated subscales described in the JOABPEQ validity
study by Fukui et al. (four items for social function, seven for mental health,
six for lumbar function, five for walking ability and four for low back pain);
Spearman's correlation matrix was used. The correlation coefficient had to be
greater than 0.40 for each item with its corresponding subscale to be
satisfactory. Scores underwent descriptive analysis, and Mann-Whitney u test was
performed to compare between categorical subgroups. RESULTS: 151 spine patients
completed the questionnaire. The mean age (range) was 34.9 (10-72) years. The
male respondents were 61 (40.4%) and the females were 90 (59.6%). The result of
Cronbach's alpha for internal consistency (reliability) was 0.87 for the 25
items. The validity was confirmed since the correlation coefficient was greater
than 0.4 for each item with only its relevant subscale. CONCLUSION: the Arabic
version of the JOABPEQ is valid, reliable and feasible in assessing patients with
spine disorders. We believe the JOABPEQ with its different versions are suitable
questionnaires to be used across nations and can serve as a unified tool in
conducting research and exchanging information in the future.
PMID- 28416190
TI - Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms.
AB - OBJECTIVE/BACKGROUND: Biomarker(s) for prediction of the future progression rate
of abdominal aortic aneurysms (AAA) may be useful to stratify the management of
individual patients. AAAs are associated with features of systemic inflammation
and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial
artery is a recognised non-invasive measurement for endothelial function. We
hypothesised that FMD is a potential biomarker of AAA progression and reflects
the temporal changes of endothelial function during AAA progression. METHODS: In
a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic
Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer
to outer) on ultrasound. Annual AAA progression was calculated by (DeltaAPD/APD
at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time
as AAA size measurement. Analyses of data were performed in the overall cohort,
and further in subgroups of AAA by size (small: 30-39 mm; moderate: 40-55 mm;
large: > 55 mm). RESULTS: FMD is inversely correlated with the diameter of AAAs
in all patients (n=162, Spearman's r=-.28, p<.001). FMD is inversely correlated
with AAA diameter progression in the future 12 months (Spearman's r=-.35,
p=.001), particularly in the moderate size group. Furthermore, FMD deteriorates
during the course of AAA surveillance (from a median of 2.0% at baseline to 1.2%
at follow-up; p=.004), while surgical repair of AAAs (n=50 [open repair n=22,
endovascular repair n=28)] leads to an improvement in FMD (from 1.1% pre
operatively to 3.8% post-operatively; p<.001), irrespective of the type of
surgery. CONCLUSION: FMD is inversely correlated with future AAA progression in
humans. FMD deteriorates during the natural history of AAA, and is improved by
surgery. The utility of FMD as a potential biomarker in the context of AAA
warrants further investigation.
PMID- 28416192
TI - Corrigendum to: Georgia's Medicaid Family Planning Waiver: Working Together with
Title X to Enhance Access to and Use of Contraceptive and Preventive Health
Services [Women's Health Issues 26 (2016) 602-611].
PMID- 28416191
TI - Editor's Choice - Assessment of International Outcomes of Intact Abdominal Aortic
Aneurysm Repair over 9 Years.
AB - BACKGROUND: Case mix and outcomes of complex surgical procedures vary over time
and between regions. This study analyses peri-operative mortality after intact
abdominal aortic aneurysm (AAA) repair in 11 countries over 9 years. METHODS:
Data on primary AAA repair from vascular surgery registries in 11 countries for
the years 2005-2009 and 2010-2013 were analysed. Multivariate adjusted logistic
regression analyses were carried out to adjust for variations in case mix.
RESULTS: A total of 83,253 patients were included. Over the two periods, the
proportion of patients >=80 years old increased (18.5% vs. 23.1%; p < .0001) as
did the proportion of endovascular repair (EVAR) (44.3% vs. 60.6; p < .0001). In
the latter period, 25.8% of AAAs were less than 5.5 cm. The mean annual volume of
open repairs per centre decreased from 12.9 to 10.6 between the two periods (p <
.0001), and it increased for EVAR from 10.0 to 17.1 (p < .0001). Overall, peri
operative mortality fell from 3.0% to 2.4% (p < .0001). Mortality for EVAR
decreased from 1.5% to 1.1% (p < .0001), but the outcome worsened for open repair
from 3.9% to 4.4% (p = .008). The peri-operative risk was greater for
octogenarians (overall, 3.6% vs. 2.1%, p < .0001; open, 9.5% vs. 3.6%, p < .0001;
EVAR, 1.8% vs. 0.7%, p < .0001), and women (overall, 3.8% vs. 2.2%, p < .0001;
open, 6.0% vs. 4.0%, p < .0001; EVAR, 1.9% vs. 0.9%, p < .0001). Peri-operative
mortality after repair of AAAs <5.5 cm was 4.4% with open repair and 1.0% with
EVAR, p < .0001. CONCLUSIONS: In this large international cohort, total peri
operative mortality continues to fall for the treatment of intact AAAs. The
number of EVAR procedures now exceeds open procedures. Mortality after EVAR has
decreased, but mortality for open operations has increased. The peri-operative
mortality for small AAA treatment, particularly open surgical repair, is still
considerable and should be weighed against the risk of rupture.
PMID- 28416193
TI - LEP rs7799039, LEPR rs1137101, and ADIPOQ rs2241766 and 1501299 Polymorphisms Are
Associated With Obesity and Chemotherapy Response in Mexican Women With Breast
Cancer.
AB - BACKGROUND: Obesity plays a major role in the pathogenesis of breast cancer.
Leptin (LEP) and adiponectin (ADIPOQ) are important in the regulation of adipose
tissue. The response to cancer treatment depends on the histological and
molecular tumor type, clinical stage, and genetic variability that might promote
carcinogenic development. The aim of this study was to investigate the
association between overweight/obesity and polymorphisms in the LEP (rs7799039),
LEP receptor (LEPR; rs1137101), and ADIPOQ genes (rs2241766, rs1501299) with the
response to breast cancer treatment in Mexican women. PATIENTS AND METHODS: A
sample of 177 patients with primary breast cancer (stage I-III) and who received
neoadjuvant therapy were included. Polymorphisms were genotyped and their serum
LEP concentrations (n = 59) were quantified. RESULTS: The patients' median age
was 53.1 years, the frequency of overweight and obesity was 57 and 84 patients,
respectively, 117 were postmenopausal, and 64 of the patients did not respond to
chemotherapy. An association of the LEP rs7799039, LEPR rs1137101, and ADIPOQ
rs1501299 polymorphisms with overweight/obesity was found. The patients who did
not respond to treatment were more frequently obese, at clinical stage III, had
metastases, and high levels of glucose. Moreover, in samples that were positive
for estrogen receptor, higher levels of LEP were found, and in wild type
genotypes for LEP rs7799039 and LEPR rs1137101. CONCLUSION: There was a direct
association between the polymorphisms in LEP rs7799039 and ADIPOQ rs1501299 with
overweight/obesity, and these genotypes affected the response to chemotherapeutic
treatment, suggesting that an obesogenic microenvironment is more favorable for
tumoral progression.
PMID- 28416196
TI - Another statin option in HIV.
PMID- 28416194
TI - Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate
Environments.
AB - Immune cells function in diverse metabolic environments. Tissues with low glucose
and high lactate concentrations, such as the intestinal tract or ischemic
tissues, frequently require immune responses to be more pro-tolerant, avoiding
unwanted reactions against self-antigens or commensal bacteria. T-regulatory
cells (Tregs) maintain peripheral tolerance, but how Tregs function in low
glucose, lactate-rich environments is unknown. We report that the Treg
transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and
glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide
adenine dinucleotide oxidation. These adaptations allow Tregs a metabolic
advantage in low-glucose, lactate-rich environments; they resist lactate-mediated
suppression of T cell function and proliferation. This metabolic phenotype may
explain how Tregs promote peripheral immune tolerance during tissue injury but
also how cancer cells evade immune destruction in the tumor microenvironment.
Understanding Treg metabolism may therefore lead to novel approaches for
selective immune modulation in cancer and autoimmune diseases.
PMID- 28416195
TI - Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia
(INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised,
double-blind, superiority trial.
AB - BACKGROUND: People living with HIV-1 infection are at greater risk for
cardiovascular disease than seronegative adults. Treatment of dyslipidaemia with
statins has been challenging in people with HIV because of an increased potential
for drug interactions due to competing cytochrome P450 metabolism between statins
and commonly used antiretroviral agents. Neither pitavastatin nor pravastatin
depend on cytochrome P450 for primary metabolism. We aimed to assess the safety
and efficacy of pitavastatin versus pravastatin in adults with HIV and
dyslipidaemia. METHODS: In the INTREPID (HIV-infected patieNts and TREatment with
PItavastatin vs pravastatin for Dyslipidemia) randomised, double-blind, active
controlled, phase 4 trial (INTREPID, we recruited adults aged 18-70 years with
controlled HIV (with CD4 counts >200 cells per MUL and HIV-1 RNA <200 copies per
mL) on antiretroviral therapy for at least 6 months and dyslipidaemia (LDL
cholesterol 3.4-5.7 mmol/L and triglycerides <=4.5 mmol/L) from 45 sites in the
USA and Puerto Rico. Patients being treated with darunavir, or who had homozygous
familial hypercholesterolaemia or any condition causing secondary dyslipidaemia,
or a history of statin intolerance, diabetes, or coronary artery disease were not
eligible. We randomly assigned patients (1:1) to pitavastatin 4 mg or pravastatin
40 mg with matching placebos once daily orally for 12 weeks, followed by a 40
week safety extension. Randomisation was stratified by viral hepatitis B or C
coinfection and computer-generated. Investigators, patients, study staff, and
those assessing outcomes were masked to treatment group. The primary endpoint was
percentage change in fasting serum LDL cholesterol from baseline to week 12 and
the primary efficacy analysis was done in the modified intention-to-treat
population. The safety analysis included all patients who took at least one dose
of study medication. This study is registered with ClinicalTrials.gov, number
NCT01301066. FINDINGS: Between Feb 23, 2011, and March 29, 2013, we randomly
assigned 252 patients to the pitavastatin (n=126) or pravastatin group (n=126).
LDL cholesterol reduction was 31.1% with pitavastatin and 20.9% with pravastatin
(least squares mean difference -9.8%, 95% CI -13.8 to -5.9; p<0.0001) at 12
weeks. At week 52, four patients (3%) in the pitavastatin group and six (5%) in
the pravastatin group had virological failure, with no significant difference
between treatments. Both treatments had neutral effects on glucose metabolism
parameters. 85 patients treated with pitavastatin (68%) and 88 patients treated
with pravastatin (70%) reported treatment-emergent adverse events, and these
caused study discontinuation in six patients (5%) versus five patients (4%). No
serious adverse event occurred in more than one participant and none were
treatment-related according to investigator assessment. The most common treatment
emergent adverse events were diarrhoea in the pitavastatin group (n=12, 10%) and
upper respiratory tract infection in the pravastatin group (n=14, 11%). 11
treatment-emergent serious adverse events were noted in seven patients (6%) in
the pitavastatin group (atrial septal defect, chronic obstructive pulmonary
disease, chest pain, diverticulitis, enterovesical fistula, gastroenteritis,
viral gastroenteritis, herpes dermatitis, multiple fractures, respiratory
failure, and transient ischaemic attack) and four events in three patients (2%)
in the pravastatin group (cerebrovascular accident, arteriosclerosis coronary
artery, myocardial infraction, and muscle haemorrhage). In the pravastatin
treatment group, one additional patient discontinued due to an adverse event
(prostate cancer that was diagnosed during the screening period, 42 days before
first dose of study treatment, and therefore was not a treatment-emergent adverse
event). INTERPRETATION: The INTREPID results support guideline recommendations
for pitavastatin as a preferred drug in the treatment of dyslipidaemia in people
with HIV. FUNDING: Kowa Pharmaceuticals America and Eli Lilly and Company.
PMID- 28416197
TI - Pre-exposure prophylaxis is approved in Scotland.
PMID- 28416198
TI - Engineering human renal epithelial cells for transplantation in regenerative
medicine.
AB - Cellular transplantation may treat several human diseases by replacing damaged
cells and/or providing a local source of trophic factors promoting regeneration.
We utilized human renal epithelial cells (hRECs) isolated from cadaveric donors
as a cell model. For efficacious implementation of hRECs for treatment of kidney
diseases, we evaluated a novel encapsulation strategy for immunoisolation of
hRECs and lentiviral transduction of the Green Fluorescent Protein (GFP) as model
gene for genetic engineering of hRECs to secrete desired trophic factors. In
specific, we determined whether encapsulation through conformal coating and/or
GFP transduction of hRECs allowed preservation of cell viability and of their
trophic factor secretion. To that end, we optimized cultures of hRECs and showed
that aggregation in three-dimensional spheroids significantly preserved cell
viability, proliferation, and trophic factor secretion. We also showed that both
wild type and GFP-engineered hRECs could be efficiently encapsulated within
conformal hydrogel coatings through our fluid dynamic platform and that this
resulted in further improvement of cell viability and trophic factors secretion.
Our findings may lay the groundwork for future therapeutics based on
transplantation of genetically engineered human primary cells for treatment of
diseases affecting kidneys and potentially other tissues.
PMID- 28416199
TI - Effect of Atrial Fibrillation on Mortality, Stroke Risk, and Quality-of-Life
Scores in Patients With Heart Failure (from the Outcomes Registry for Better
Informed Treatment of Atrial Fibrillation [ORBIT-AF]).
AB - The degree to which clinical outcomes are worsened in patients with atrial
fibrillation (AF) with heart failure (HF) compared with those without HF is not
well described. This study aimed to determine the impact of HF on clinical
outcomes in patients with AF. We analyzed data from Outcomes Registry for Better
Informed Treatment of Atrial Fibrillation, a national registry of 10,135 patients
with AF to determine associations between HF and left ventricular ejection
fraction (LVEF) and outcomes, including stroke, mortality, and hospitalization
using Cox multivariable modeling. Atrial Fibrillation Effect on Quality-of-Life
Questionnaire (AFEQT) scores between groups were also compared. Overall, 33% (n =
3,203) of patients had HF; of these 33% (n = 985) had LVEF <=40%. Oral
anticoagulation was prescribed more commonly in patients with HF (81% vs 74%).
Compared with patients without HF, those with HF had similar rate of stroke (1.28
vs 0.88 per 100-patient years, hazard ratio [HR] 1.11, confidence interval [CI]
0.83 to 1.48, p = 0.47) but higher mortality (HR 1.69, CI 1.49 to 1.92, p <0.001)
and hospitalization (HR 1.31, CI 1.23 to 1.39, p <0.0001). Patients with LVEF
<=40% had similar stroke risk (HR 1.06, CI 0.67 to 1.67) but higher mortality (HR
2.06, CI 1.74 to 2.44) and hospitalization (HR 1.38, CI 1.25 to 1.51). AFEQT
overall score was significantly lower (76.9 vs 83.3, p <0.0001) in patients with
HF. In conclusion, HF was associated with increased risk of death and
hospitalization and worse quality of life, but similar rates of thromboembolism
regardless of LVEF among patients with AF. These findings highlight the need to
develop therapeutic strategies targeting functional status and survival for
patients with HF and AF.
PMID- 28416200
TI - Comparison of QRS Duration and Associated Cardiovascular Events in American
Indian Men Versus Women (The Strong Heart Study).
AB - Electrocardiographic QRS duration at rest is associated with sudden cardiac death
and death from coronary heart disease in the general population. However, its
relation to cardiovascular events in American Indians, a population with
persistently high cardiovascular disease mortality, is unknown. The relation of
QRS duration to incident cardiovascular disease during 17.2 years of follow-up
was assessed in 1,851 male and female Strong Heart Study participants aged 45 to
74 years without known cardiovascular disease at baseline. Cox regression with
robust standard error estimates was used to determine the association between
quintiles of QRS duration and incident cardiovascular disease in gender
stratified analyses, adjusted for age, systolic blood pressure, hypertension,
antihypertensive medication use, body mass index, current smoking, diabetes,
total cholesterol, high-density lipoprotein cholesterol, and albuminuria. In
women only, QRS duration in the highest quintile (>=105 ms) conferred
significantly higher risk of cardiovascular disease than QRS duration in the
lowest quintile (64 to 84 ms) (hazard ratio 1.6, 95% CI 1.1 to 2.4) likely
because of higher risks of coronary heart disease (hazard ratio 1.8, 95% CI 1.1
to 3.1) and myocardial infarction (hazard ratio 2.1, 95% CI 1.0 to 4.7).
Furthermore, when added to the Strong Heart Study Coronary Heart Disease Risk
Calculator, QRS duration significantly improved prediction of future coronary
heart disease events in women (Net Reclassification Index 0.17, 95% CI 0.06 to
0.47). In conclusion, QRS duration is an independent predictor of cardiovascular
disease in women in the Strong Heart Study cohort and may have value in
estimating risk in populations with similar risk profiles and a high lifetime
incidence of cardiovascular disease.
PMID- 28416201
TI - The impact of the Nurse Faculty Scholars program on schools of nursing.
AB - BACKGROUND: The Robert Wood Johnson Foundation Nurse Faculty Scholars program was
conceptualized as not only promoting the growth and development of early-career
faculty but as enhancing the research infrastructure of scholars' schools of
nursing. PURPOSE: At the completion of the scholars' three years of support,
deans/directors were asked to provide feedback regarding the institutional impact
of the scholars' participation in the program. METHODS: Phone interviews were
conducted on the first five completed cohorts and a six-item questionnaire was
developed to obtain some quantitative data. DISCUSSION: The program was viewed as
having accelerated the scholars' leadership and scholarship, and their influence
within the school/university and regionally/nationally. Deans/directors generally
agreed that the scholars' experience helped build the school's research
portfolio. CONCLUSION: Looking back on how the participating schools of nursing
fared, one can say that the program's institutional expectations were achieved
most of the time. The program helped scholars build their own reputations and
that in turn had consequences for the school's standing as a whole. A number of
components are described that can be replicated singly or in various combinations
by schools/universities interested in adopting aspects of this program.
PMID- 28416202
TI - Presenteeism in nursing: An evolutionary concept analysis.
AB - BACKGROUND: Presenteeism is an emerging concept in nursing that has been linked
to increased health care costs, patient medication errors and falls, and negative
nurse well-being. However, prior work has utilized various definitions and
antecedents. Clarity on the significance, development, and consequences of
presenteeism in nursing is needed. PURPOSE: This concept analysis seeks to
understand the application of presenteeism within nursing workforce literature
and in the broader workforce context. METHOD: Rodgers' evolutionary concept
analysis method was used. DISCUSSION: The proposed definition of presenteeism as
the act of being physically present at work with reduced performance can be
attributed to multiple antecedents. These include nurse health, professional
identity, work-life balance, and work environment. The prevalence of these
antecedents with high rates of presenteeism among nurses and consequences point
to the need for interventions. CONCLUSION: These findings can guide development
of future interventions and policies that address the broader context of factors
leading to presenteeism.
PMID- 28416203
TI - The S4---S5 linker - gearbox of TRP channel gating.
AB - Transient receptor potential (TRP) channels are cation channels which participate
in a wide variety of physiological processes in organisms ranging from fungi to
humans. They fulfill roles in body homeostasis, are sensors for noxious chemicals
and temperature in the mammalian somatosensory system and are activated by light
stimulated phospholipase C activity in Drosophila or by hypertonicity in yeast.
The transmembrane topology of TRP channels is similar to that of voltage-gated
cation channels. TRP proteins assemble as tetramers with each subunit containing
six transmembrane helices (S1-S6) and intracellular N- and C-termini. Here we
focus on the emerging functions of the cytosolic S4-S5 linker on TRP channel
gating. Most of this knowledge comes from pathogenic mutations within the S4-S5
linker that alter TRP channel activities. This knowledge has stimulated forward
genetic approaches to identify additional residues around this region which are
essential for channel gating and is supported, in part, by recent structures
obtained for TRPV1, TRPV2, TRPV6, TRPA1, and TRPP2.
PMID- 28416204
TI - "They must understand we are people": Pregnancy and maternity service use among
signing Deaf women in Cape Town.
AB - BACKGROUND: Women with disabilities are at disproportionate risk for adverse
pregnancy outcomes, however, there is limited information on their pregnancy
histories. This mixed-methods study focuses on signing Deaf women whose access to
health care may be compromised by language barriers related to their disability.
OBJECTIVE: To describe and compare the pregnancy outcomes and maternity service
use of a sample of signing Deaf women of child-bearing age in Cape Town to the
population of the Western Cape of South Africa. METHODS: We interviewed 42 Deaf
women selected by non-probability snowball sampling, using a structured
questionnaire in South African Sign Language in Cape Town in July 2016. RESULTS:
Average parity of the sample was similar to that of the Western Cape population.
Most women had one or two children (74%). Thirty-one percent of women had
experienced a miscarriage and 19% had terminated a pregnancy. Almost all women
(96%) attended at least one antenatal appointment during their pregnancies, and
all deliveries occurred at a health facility. Women primarily relied on writing
to communicate during antenatal visits and labor/delivery. The majority of women
reported communication issues due to limited interpretation services, and some
reported experiencing mistreatment from hospital staff. CONCLUSION: This study
provides novel information on the pregnancy histories of Deaf women. While
maternal service usage was high, the quality of services were inadequate with
reports of linguistic barriers and mistreatment. Findings suggest the need to
improve maternity care for Deaf women through implementing interpretation
services and providing sensitivity training to health care providers.
PMID- 28416206
TI - Reversible Interferon-Induced Pulmonary Arterial Hypertension in a Patient With
Multiple Sclerosis.
PMID- 28416207
TI - Reflections on the Implementation of Low-Dose Computed Tomography Screening in
Individuals at High Risk of Lung Cancer in Spain.
AB - Lung cancer (LC) is a major public health issue. Despite recent advances in
treatment, primary prevention and early diagnosis are key to reducing the
incidence and mortality of this disease. A recent clinical trial demonstrated the
efficacy of selective screening by low-dose computed tomography (LDCT) in
reducing the risk of both lung cancer mortality and all-cause mortality in high
risk individuals. This article contains the reflections of an expert group on the
use of LDCT for early diagnosis of LC in high-risk individuals, and how to
evaluate its implementation in Spain. The expert group was set up by the Spanish
Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of
Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish
Society of Medical Oncology (SEOM).
PMID- 28416205
TI - The link between schizophrenia and substance use disorder: A unifying hypothesis.
AB - Substance use disorders occur commonly in patients with schizophrenia and
dramatically worsen their overall clinical course. While the exact mechanisms
contributing to substance use in schizophrenia are not known, a number of
theories have been put forward to explain the basis of the co-occurrence of these
disorders. We propose here a unifying hypothesis that combines recent evidence
from epidemiological and genetic association studies with brain imaging and pre
clinical studies to provide an updated formulation regarding the basis of
substance use in patients with schizophrenia. We suggest that the genetic
determinants of risk for schizophrenia (especially within neural systems that
contribute to the risk for both psychosis and addiction) make patients vulnerable
to substance use. Since this vulnerability may arise prior to the appearance of
psychotic symptoms, an increased use of substances in adolescence may both
enhance the risk for developing a later substance use disorder, and also serve as
an additional risk factor for the appearance of psychotic symptoms. Future
studies that assess brain circuitry in a prospective longitudinal manner during
adolescence prior to the appearance of psychotic symptoms could shed further
light on the mechanistic underpinnings of these co-occurring disorders while
identifying potential points of intervention for these difficult-to-treat co
occurring disorders.
PMID- 28416208
TI - Fetal and perinatal stem cells in cardiac regeneration: Moving forward to the
paracrine era.
AB - Cardiovascular disease (CD) is a major burden for Western society. Regenerative
medicine has provided encouraging results, yet it has not addressed the focal
defects causing CD and mainly related to the inefficient repair programme of the
heart. In this scenario, stem cells have been broadly investigated and their
paracrine effect proposed as a possible working strategy to boost endogenous
mechanisms of repair and regeneration from within the cardiac tissue. The
scientific community is now focusing on identifying the most effective stem cell
secretome, as the whole of bioactive factors and extracellular vesicles secreted
by stem cells and endowed with regenerative potential. Indeed, the adult stem
cell-paracrine potential for cardiac regeneration have been widely analyzed with
positive outcome. Nevertheless, low yield, invasive sampling and controversial
self-renewal may limit adult stem cell application. On the contrary, fetal and
perinatal stem cells, which can be easily isolated from leftover sample via
prenatal screening during gestation or as clinical waste material after birth,
can offer an ideal alternative. These broadly multipotent immature progenitors
share features with both adult and embryonic stem cells, show high self-renewal,
but they are not tumorigenic neither cause any ethical concern. While fetal and
perinatal stem cells demonstrated to improve cardiac function when injected in
the injured heart, the comprehensive characterization of their secretome for
future applications is still at its infancy. In this review, we will discuss the
paracrine potential of the fetal and perinatal stem cell secretome to provide
cardiac repair and resurge the dormant mechanisms of cardiac regeneration for
future therapy.
PMID- 28416209
TI - [Is the formal quality of multiple choice questions used for continuing medical
education influenced by guidelines for authors provided by the publishing
houses?]
AB - INTRODUCTION: The widespread use of flawed multiple choice questions (MCQs) in
continuing medical education (CME) has been demonstrated in different studies. In
recent years, quality control measures have been established by some German
publishing houses to ensure the quality of MCQs. OBJECTIVES: The purpose of the
present study is to evaluate whether the quality of author's guidelines and the
quality of MCQs correlate and whether the quality of MCQs in CME has improved
following the implementation of quality control measures. MATERIALS AND METHODS:
A set of 720 items from 6 journals was selected for analysis. A list of 10 item
writing flaws provided by Kuhne-Eversmann et al. was modified. The existing
guidelines for authors of the six selected journals were categorized by their
comprehensiveness. RESULTS: There were substantial differences in item quality
with the percentage of flawed items ranging between 34 % and 92 % of all items
published by a journal. One journal showed considerable improvement of item
quality following the implementation of guidelines for authors (61 % flawed items
in 2006 vs. 33% in 2012). The comprehensiveness of the author's guidelines
correlated negatively with the number of item-writing flaws. CONCLUSIONS: The
correlation between the existence of elaborate guidelines for authors and the
absence of item-writing flaws in MCQs suggests that the publication of guidelines
for authors could result in a higher quality of MCQs, even though the review
process might have a major influence.
PMID- 28416210
TI - Development of a continuous motorcycle protection barrier system using computer
simulation and full-scale crash testing.
AB - Road restraint systems are designed to minimize the undesirable effects of
roadside accidents and improve safety of road users. These systems are utilized
at either side or median section of roads to contain and redirect errant
vehicles. Although restraint systems are mainly designed against car, truck and
bus impacts there is an increasing pressure by the motorcycle industry to
incorporate motorcycle protection systems into these systems. In this paper
development details of a new and versatile motorcycle barrier, CMPS, coupled with
an existing vehicle barrier is presented. CMPS is intended to safely contain and
redirect motorcyclists during a collision event. First, crash performance of CMPS
design is evaluated by means of a three dimensional computer simulation program
LS-DYNA. Then full-scale crash tests are used to verify the acceptability of CMPS
design. Crash tests were performed at CSI proving ground facility using a
motorcycle dummy in accordance with prEN 1317-8 specification. Full-scale crash
test results show that CMPS is able to successfully contain and redirect dummy
with minimal injury risk on the dummy. Damage on the barrier is also minimal
proving the robustness of the CMPS design. Based on the test findings and further
review by the authorities the implementation of CMPS was recommended at highway
system.
PMID- 28416211
TI - Phenotypic heterogeneity of human retinal pigment epithelial cells in passaged
cell populations.
AB - Human retinal pigment epithelial (RPE) cells at different population doublings
(PDs) were cultured for 28 days to examine their phenotypic heterogeneity in a
confluent state. In an early population (PD = 2.8), cells showed a cobblestone
like appearance (type I), which gradually became small and tight, and eventually
exhibited dark pigmentation. Some cells showed a dome-like structure (type II),
which detached from the culture surface during culture. With increasing PD, the
cells showed active migration that caused a shift in phenotype from a single
layer of large, flattened cells (type III) to a multiple cell layers (stratified)
with flattened, irregularly shaped cells (type IV). Immunostaining of specific
RPE markers, ZO-1 and Na+/K+-ATPase revealed that cells have markedly decreased
expressions in a late population (PD = 10.1). RPE phenotypes were classified into
four types by measuring the nuclear size and local density. The frequencies of
type I cells decreased with increasing PD value, while the frequencies of type
III and IV cells increased along with the decrease in type I. The frequencies of
type IV cells at PD = 10.1 had increased by 10.3-fold compared with PD = 2.8.
From these results, the nuclear size and local density were proposed as
indicators for understanding phenotypic heterogeneity of RPE cells in the
passaged cell population during cell expansion. It is concluded that the
population doubling level is an important factor to affect the transition of RPE
phenotype and thereby to modulate the quality of cultured cells.
PMID- 28416212
TI - Conversion of vegetable wastes to organic acids in leaching bed reactor:
Performance and bacterial community analysis.
AB - Vegetable wastes (VWs), which contained abundant solid content, were digested in
a leaching bed reactor (LBR). The tested VWs for acidification in the LBR
included cabbage, potato, and tomato vine. The digestion in the LBR was carried
out at the same organic loading rate of 25 g volatile solid (VS) per liter. It
was found that cabbage and potato produced much more volatile fatty acids (VFAs)
than tomato vine, probably because readily degradable components were more
abundant in cabbage and potato. The retention time to digest each feedstock was
different. It took 4, 5, and 8 days for cabbage, potato, and tomato vine to
completely disappear in the reactor, respectively. The profiles of the VFAs
generated from the three VWs were examined. In all cases, the predominant VFAs
were acetic acid and butyric acid, although the relative abundance of individual
VFA varied across the tested leachate samples. The bacterial community
compositions of the leachates were analyzed by high throughput sequencing, and it
was found that the feedstock strongly affected the bacterial community structure
in the acidogenic process. All leachates had distinct bacterial community
structure, although they did share a common set of core communities that included
Proteobacteria, Firmicutes, and Bacteroidetes.
PMID- 28416214
TI - Corrigendum to 'Nothing to (S)cough at: Pulmonary Mycobacterium avium complex
infection' Am J Med. 2017;130(2):153-156.
PMID- 28416213
TI - A prospective study of Rivaroxaban for central venous catheter associated upper
extremity deep vein thrombosis in cancer patients (Catheter 2).
AB - INTRODUCTION: Patients with cancer are at increased risk of thrombosis,
particularly those with central venous catheter (CVC) placement, which may
predispose to the development of upper extremity deep vein thrombosis (UEDVT).
Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged
to warfarin. The direct oral anticoagulants (DOACs) have become standard of care
for uncomplicated venous thromboembolism (VTE), but research in patients with
cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with
cancer who develop UEDVT due to CVC for preservation of line function, and safety
outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS:
Patients >=18years of age with active malignancy and symptomatic proximal UEDVT
with or without pulmonary embolism (PE), associated with a CVC, were eligible.
Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg
oral daily for 9weeks. Patients were followed clinically for 12weeks to assess
for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47
women) were included, with mean age 54.1years. The most common malignancy was
breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk
of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients
(12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed
promise in treating CVC-UEDVT in cancer patients, resulting in preserved line
function. However, bleeding rates and a fatal pulmonary embolism on treatment are
concerning safety outcomes necessitating further study before rivaroxaban can be
recommended.
PMID- 28416215
TI - Stir bar sorptive extraction and liquid chromatography-tandem mass spectrometry
determination of polar and non-polar emerging and priority pollutants in
environmental waters.
AB - An analytical method based on stir bar sorptive extraction (SBSE) was developed
and validated for the determination of environmental concern pollutants in
environmental waters by liquid chromatography-tandem mass spectrometry (LC
MS/MS). Target compounds include six water and oil repellents (perfluorinated
compounds), four preservatives (butylated hydroxytoluene and three parabens), two
plasticizers (bisphenol A and di(2-ethylhexyl)phthalate), seven surfactants (four
linear alkylbenzene sulfonates, nonylphenol and two nonylphenol ethoxylates), a
flame retardant (hexabromocyclododecane), four hormones, fourteen pharmaceutical
compounds, an UV-filter (2-ethylhexyl 4-methoxycinnamate) and nine pesticides. To
achieve the simultaneous extraction of polar and non-polar pollutants two stir
bar coatings were tested, the classic polydimethylsiloxane (PDMS) coating and the
novel ethylene glycol modified silicone (EG-silicone). The best extraction
recoveries were obtained using EG-silicone coating. The effects of sample pH,
volume and ionic strength and extraction time on extraction recoveries were
evaluated. The analytical method was validated for surface water and tap water
samples. The method quantification limits ranged from 7.0ngL-1 to 177ngL-1. The
inter-day precision, expressed as relative standard deviation, was lower than
20%. Accuracy, expressed as relative recovery values, was in the range from 61 to
130%. The method was applied for the determination of the 48 target compounds in
surface and tap water samples.
PMID- 28416216
TI - 3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: A fascinating molecular
framework to study the enantioseparation ability of the amylose (3,5
dimethylphenylcarbamate) chiral stationary phase. Part II. Solvophobic effects in
enantiorecognition process.
AB - The enantiomers of five chiral compounds incorporating the 3-(phenyl-4-oxy)-5
phenyl-4,5-dihydro-(1H)-pyrazole scaffold and differing only in the linear alkyl
chain (varying in length from 1 to 5 carbon atoms) linked to the oxygen atom were
directly separated on the amylose (3,5-dimethylphenylcarbamate) based Chiralpak
AD-3 chiral stationary phase. The effects of the mobile phase composition, the
structure of the analytes and temperature on the retention and enantioselectivity
were investigated. It was found that the enantiomeric separations were in all
cases enthalpy-driven and disfavored by entropic term. U-shape curves obtained by
plotting the chromatographic data versus the alcoholic percentage in n-pentane
methanol and n-hexane-ethanol mobile phases highlighted that, at higher alcohol
concentrations, solvophobic interactions were operative in the retention
mechanism. The unusual trend of such curves was linked to the nature of alkyl
chain of the pyrazolines and it was indicative of the solvophobic contribution to
the achievement of a high degree of enantioseparation.
PMID- 28416217
TI - Overcoming "speed limits" in high throughput chromatographic analysis.
AB - The combination of high speed autosampler technology and ultrafast
chromatographic separations enables faster high throughput analysis. With an
injection cycle time of 10.6 s, MISER (Multiple Injection in a Single
Experimental Run) HPLC-MS analysis of a 96 well microplate can be completed in
only 17min. As chromatographic separations in the sub 5s range become
increasingly common, even faster autosamplers will be needed to realize further
speed improvements in high throughput LC-MS analysis. Indeed with proper hardware
sampling approaches, chromatographic analysis of microplates could approach
speeds of spectrophotometric plate readers while maintaining the advantage of
multicomponent detection and monitoring.
PMID- 28416218
TI - Dummy molecularly imprinted microbeads as solid-phase extraction material for
selective determination of phthalate esters in water.
AB - The aim of this study was to investigate the usability of newly synthesized dummy
molecularly imprinted microbeads (DMIMs) as a solid phase extraction (SPE)
material to determine six phthalate esters (PEs) in water by GC-MS analysis.
Diethyl phthalate (DEP) was used as a dummy template to prepare poly(ethylene
glycol dimethacrylate N-methacryloyl-l-tryptophan methyl ester) [PEMATrp)] DMIMs
by using suspension polymerization. The PEMATrp DMIMs were characterized by using
Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy
(XPS) and scanning electron microscopy (SEM). Firstly, the adsorption capacities
of the DMIMs prepared in different template molecule (DEP) to functional monomer
(MATrp) ratios were investigated by using DEP solutions in the concentration
range of 1-500mg/L at pH 3.0. Styrene and vanillic acid were used to evaluate the
selectivity of the prepared DMIMs towards the template molecule (DEP). Then, the
best analytical conditions were investigated for the simultaneous determination
of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP),
benzylbutyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl
phthalate (DnOP) in aqueous media by using the PEMATrp DMIMs as SPE material.
Validation experiments showed that the PEMATrp DMIMs-SPE method had good
linearity at 12.5-250.0MUg/L (0.988-0.999), good precision (1.2-5.9%), and limits
of detection in a range of 0.31-0.41MUg/L.
PMID- 28416219
TI - Displacement of sexual partnerships in trials of sexual behavior interventions: A
model-based assessment of consequences.
AB - We investigated the impact of the displacement of sexual activity from adherent
recipients of an intervention to others within or outside a trial population on
the results from hypothetical trials of different sexual behavior interventions.
A short-term model of HIV-prevention interventions that lead to female rejection
of male partnership requests showed the impact of displacement expected at the
start of a trial. An agent-based model, with sexual mixing and other South
African specific demographics, evaluated consequences of displacement for sexual
behavior interventions targeting young females in South Africa. This model
measured the cumulative incidence among adherent, non-adherent, control and non
enrolled females in a hypothetical trial of HIV prevention. When males made more
than one attempt to seek a partnership, interventions reduced short-term HIV
infection risk among adherent females, but increased it among non-adherent
females as well as controls, non-enrolled (females eligible for the trial but not
chosen to participate) and ineligible females (females that did not qualify for
the trial due to age). The impact of displacement depends on the intervention and
the adherence. In both models, the risk to individuals who are not members of the
adherent intervention group will increase with displacement leading to a biased
calculation for the effect estimates for the trial. Likewise, intent-to-treat
effect estimates become nonlinear functions of the proportion adherent.
PMID- 28416220
TI - Treatment of chronic hepatitis C: can complexity pave the way towards
elimination?
PMID- 28416221
TI - Ombitasvir, paritaprevir, and ritonavir plus dasabuvir for 8 weeks in previously
untreated patients with hepatitis C virus genotype 1b infection without cirrhosis
(GARNET): a single-arm, open-label, phase 3b trial.
AB - BACKGROUND: Clinical studies have shown high rates of sustained virological
response (hepatitis C virus [HCV] RNA <15 IU/mL) at post-treatment week 12
(SVR12) in patients with genotype 1b infection with and without cirrhosis who
received coformulated ombitasvir, paritaprevir, and ritonavir, plus dasabuvir,
without ribavirin, for 12 weeks. In this study, we aimed to assess 8-week
treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without
ribavirin in patients infected with HCV genotype 1b without cirrhosis. METHODS:
We did a multicentre, open-label, single-arm, phase 3b study (GARNET) in 20
hospitals or clinics in Australia, Canada, France, Germany, Israel, Italy, Spain,
and the UK, to assess the safety and efficacy of an 8-week treatment duration of
once-daily oral ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, plus
twice-daily oral dasabuvir 250 mg in previously untreated patients with chronic
HCV genotype 1b infection without cirrhosis (as assessed by liver biopsy,
transient elastography, or serum markers). Eligible patients were aged at least
18 years, with more than 1000 IU/mL HCV RNA, and a laboratory result at screening
indicating infection with HCV genotype 1b subtype only. Patients were excluded if
they had evidence of HCV genotype or subtype other than genotype 1b, if they
tested positive for hepatitis B surface antigen or anti-HIV antibody at
screening, or if they had previously been treated for HCV. The primary endpoint
was the proportion of patients with SVR12; the primary endpoint and safety were
assessed in all patients who received at least one dose of study drugs. This
trial is registered with ClinicalTrials.gov, number NCT02582632. FINDINGS:
Patients were screened between Nov 24, 2015, and March 1, 2016, and 166 patients
were enrolled. 163 (98%) of 166 enrolled patients had HCV genotype 1b infection,
and three (2%) of 166 had other genotypes or subtypes (genotype 1a, genotype 1d,
and genotype 6). All enrolled patients received at least one dose of study drugs.
162 (98% [95% CI 95.3-99.9]) of 166 patients achieved SVR12. One patient
discontinued treatment on day 45 due to adverse events. Most adverse events were
mild in severity, and the most common adverse events were headache (35 [21%] of
166) and fatigue (28 [17%] of 166). Two (1%) of 166 patients had serious adverse
events; neither were considered related to study drug treatment. INTERPRETATION:
Treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without
ribavirin, for 8 weeks was efficacious and well tolerated. 8-week treatment
options for previously untreated patients with HCV genotype 1b infection without
cirrhosis are limited; shortening the treatment duration might reduce the burden
associated with medical visits and procedures, thereby improving access to care
and enabling the treatment of more patients. FUNDING: AbbVie.
PMID- 28416223
TI - Study on emission of hazardous trace elements in a 350 MW coal-fired power plant.
Part 2. arsenic, chromium, barium, manganese, lead.
AB - Hazardous Trace elements (HTEs) emitted from coal combustion has raised
widespread concern. Studies on the emission characteristics of five HTEs, namely
arsenic (As), chromium (Cr), barium (Ba), manganese (Mn), lead (Pb) at three
different loads (100%, 83%, 71% output) and different coal types were performed
on a 350 MW coal-fired power plant equipped with SCR, ESP + FF, and WFGD. HTEs in
the flue gas at the inlet/outlet of each air pollution control device (APCD) were
sampled simultaneously based on US EPA Method 29. During flue gas HTEs sampling,
coal, bottom ash, fly ash captured by ESP + FF, fresh desulfurization slurry,
desulfurization wastewater were also collected. Results show that mass balance
rate for the system and each APCD is in an acceptable range. The five studied
HTEs mainly distribute in bottom and ESP + FF ash. ESP + FF have high removal
efficiency of 99.75-99.95%. WFGD can remove part of HTEs further. Total removal
rate across the APCDs ranges from 99.84 to 99.99%. Concentration of HTEs emitted
to atmosphere is within the extremely low scope of 0.11-4.93 MUg/m3. Emission
factor of the five studied HTEs is 0.04-1.54 g/1012J. Content of As, Pb, Ba, Cr
in solid samples follows the order of ESP + FF ash > bottom ash > gypsum. More
focus should be placed on Mn in desulfuration wastewater, content of which is
more than the standard value. This work is meaningful for the prediction and
removal of HTEs emitted from coal-fired power plants.
PMID- 28416222
TI - Dentin on the nanoscale: Hierarchical organization, mechanical behavior and
bioinspired engineering.
AB - OBJECTIVE: Knowledge of the structural organization and mechanical properties of
dentin has expanded considerably during the past two decades, especially on a
nanometer scale. In this paper, we review the recent literature on the
nanostructural and nanomechanical properties of dentin, with special emphasis in
its hierarchical organization. METHODS: We give particular attention to the
recent literature concerning the structural and mechanical influence of collagen
intrafibrillar and extrafibrillar mineral in healthy and remineralized tissues.
The multilevel hierarchical structure of collagen, and the participation of non
collagenous proteins and proteoglycans in healthy and diseased dentin are also
discussed. Furthermore, we provide a forward-looking perspective of emerging
topics in biomaterials sciences, such as bioinspired materials design and
fabrication, 3D bioprinting and microfabrication, and briefly discuss recent
developments on the emerging field of organs-on-a-chip. RESULTS: The existing
literature suggests that both the inorganic and organic nanostructural components
of the dentin matrix play a critical role in various mechanisms that influence
tissue properties. SIGNIFICANCE: An in-depth understanding of such nanostructural
and nanomechanical mechanisms can have a direct impact in our ability to evaluate
and predict the efficacy of dental materials. This knowledge will pave the way
for the development of improved dental materials and treatment strategies.
CONCLUSIONS: Development of future dental materials should take into
consideration the intricate hierarchical organization of dentin, and pay
particular attention to their complex interaction with the dentin matrix on a
nanometer scale.
PMID- 28416224
TI - Post-discharge kidney function is associated with subsequent ten-year renal
progression risk among survivors of acute kidney injury.
AB - The extent to which renal progression after acute kidney injury (AKI) arises from
an initial step drop in kidney function (incomplete recovery), or from a long
term trajectory of subsequent decline, is unclear. This makes it challenging to
plan or time post-discharge follow-up. This study of 14651 hospital survivors in
2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent
renal decline by using the post-discharge estimated glomerular filtration rate
(eGFR) rather than the pre-admission as a new reference point for determining
subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo
CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death
was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4
(4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline
was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs
no AKI) was greatest among those with higher post-discharge eGFRs with
multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68
1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30,
respectively. The excess risk after AKI persisted over ten years of study,
irrespective of AKI severity, or post-episode proteinuria. Thus, even if post
discharge kidney function returns to normal, hospital admission with AKI is
associated with increased renal progression that persists for up to ten years.
Follow-up plans should avoid false reassurance when eGFR after AKI returns to
normal.
PMID- 28416227
TI - Association between current smoking and cognitive impairment depends on age: A
cross-sectional study in Xi'an, China.
AB - BACKGROUND: Cigarette smoking is a modifiable risk factor for cognitive
impairment, while the relationship between current smoking and cognitive
impairment is not fully understood. The objectives were to identify a possible
association between current smoking and cognitive impairment depending on age in
the Chinese rural population. METHODS: Data for the study consisted of 1,782
participants (40 years and older) who lived in a rural village in the vicinity of
Xi'an, China. Data about smoking history and cognitive function were collected.
Cognitive function was scored by the Mini-Mental State Examination. The effect of
age on the relationship between current smoking and cognitive impairment was
analyzed with interaction and stratified analysis by logistic regression models.
RESULTS: Interaction analysis showed that current smoking is positively related
with cognitive impairment (odds ratio [OR]=9.067; 95% confidence interval [95%
CI] 1.305-62.979; P=.026). However, the interaction term, age by current smoking,
is negatively related with cognitive impairment (OR=0.969; 95%CI 0.939-0.999;
P=.045). Stratified logistic regression showed that in the 40-65 years of age
sublayer, OR of current smoking is 1.966 (P=.044), whereas in the>65 years of age
sublayer, the OR is 0.470 (P=.130). This means that the association between
current smoking and cognitive impairment with age might be positive (OR>1) in
lower age sublayers, but no significant difference in higher age sublayers.
CONCLUSIONS: In conclusion, current smoking might be positively associated with
cognitive impairment in the middle-aged but the relationship declines with
increasing age.
PMID- 28416228
TI - Cat scratch disease. Onset as epithroclear tumor.
PMID- 28416226
TI - Klotho restoration via acetylation of Peroxisome Proliferation-Activated Receptor
gamma reduces the progression of chronic kidney disease.
AB - Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho
expression closely correlates with the development and progression of chronic
kidney disease (CKD). Klotho is also a downstream gene of Peroxisome
Proliferation-Activated Receptor gamma (PPARgamma), a major transcription factor
whose functions are significantly affected by post-translational modifications
including acetylation. However, whether PPARgamma acetylation regulates renal
Klotho expression and function in CKD is unknown. Here we test whether renal
damage and reduced Klotho expression in the adenine CKD mouse model can be
attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A. This
inhibition up-regulated Klotho mainly through an enhancement of PPARgamma
acetylation, stimulation of PPARgamma binding to Klotho promoter, and PPARgamma
dependent increase in Klotho transcription, with a substantial control of the
regulation occurring via PPARgamma acetylations on K240 and K265. Consistently
trichostatin A-induced reversal of Klotho loss and renoprotective effects were
abrogated in PPARgamma knockout mice, supporting that PPARgamma is an essential
acetylation target for Klotho restoration and renal protection. Intriguingly, the
kidneys of adenine-fed CKD mice displayed deregulated HDAC3 up-regulation.
Selective HDAC3 inhibition effectively alleviated Klotho loss and kidney injury,
whereas the protective effects were largely abolished when Klotho was knocked
down by siRNA, suggesting that aberrant HDAC3 and Klotho loss are crucial
components involved in the renal damage of mice with CKD. Our study identified an
important signaling cascade and key components contributing to the pathogenesis
of CKD. Thus, targeting Klotho loss by HDAC3 inhibition has promising therapeutic
potential for the reduction of CKD progression.
PMID- 28416225
TI - B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic
disease in a rat model of polycystic kidney disease.
AB - Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion
and fibrosis, frequently leading to end-stage renal disease. Increased
vasopressin and cAMP signaling, dysregulated calcium homeostasis, and
hypertension play major roles in PKD progression. The guanylyl cyclase A agonist,
B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti
hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD
pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on
PKD progression in a rat model of PKD. Sustained BNP production significantly
reduced kidney weight, renal cystic indexes and fibrosis, in concert with
suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic
epithelial cell proliferation, suppressed fibrotic gene expression, and increased
intracellular calcium. Together, our data demonstrate multifaceted effects of
sustained activation of guanylyl cyclase A on polycystic kidney and liver
disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel
therapeutic strategy for hepatorenal fibrocystic diseases.
PMID- 28416229
TI - Recurrent laryngeal nerve paralysis in a lung cancer patient: A cause of
contralateral vocal cord hypermetabolism on PET/CT.
PMID- 28416230
TI - Porphyria cutanea tarda in a patient with hepatitis C.
PMID- 28416231
TI - Unilateral neuroretinitis.
PMID- 28416232
TI - Experience in real clinical practice with new direct acting antivirals in chronic
hepatitis C.
AB - INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical
practice in patients with chronic HCV (CHC) has been a milestone in medicine.
PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with
chronic HCV treated with direct-acting antivirals. Efficacy and safety of
treatment and factors associated with failure treatment were evaluated. RESULTS:
Age 54+/-10. Male (70%). Cirrhosis (60%). Distribution according to genotypes:
G1a (31%), G1b (42%); G3 (14%); G4 (13%). Child-Pugh B and C (n=15). Naive (56%).
SVR rate was (87.3%): Child-A (91%), Child-B (75%) and Child-C (60%). The best
cure rates were achieved with a 3D/2D+/-ribavirin (SVR=97.4%;n=39) and
sofosbuvir/ledipasvir+/-ribavirin (RVS=93.1%; n=29) combination. An SVR rate of
<90% was achieved with sofosbuvir+simeprevir+/-ribavirin (SVR=88%, n=25),
simeprevir+daclatasvir+/-ribavirin 73%, n=15). The association of ribavirin to
these last three therapeutic options (n=19) improved cure rates (SVR=94.7%,
18/19) compared to its absence (n=39;SVR=77%). Improvement in MELD (40%). Output
transplant list (20%). Substitutions associated with resistors NS3: G1a
(positions 80K; n=5); G1b and G4 (position 168 and 36; n=4), while for NS5a: G1a
(position 30; n=2) and G1b and G3 (position 93; n=3). Variables associated with
failure in multivariate analysis (p<0.05): presence of ascites, G3 and ribavirin
dosage<600mg/day. DISCUSSION: The presence of genotype 3, ascites or dosage of
ribavirin<600mg/day were associated with higher failure rates. The use of
ribavirin>600mg/day in cirrhotic G1 or G3, who will be treated with
sofosbuvir+simeprevir or daclatasvir is recommended where no baseline resistance
test is available.
PMID- 28416233
TI - Multiple syphilitic chancre.
PMID- 28416234
TI - Orbit lymphomas in Spanish population. Descriptive study and side effects of
treatment with radiotherapy.
PMID- 28416235
TI - Supplementation of vitamin D and reduction of analgesic requirements in
institutionalized elderly with chronic musuloskeletal pain.
PMID- 28416236
TI - Cardiac tamponade. A complication of treatment with infliximab.
PMID- 28416237
TI - Proliferative verrucous leukoplakia of the tongue.
PMID- 28416238
TI - Pulmonary involvement in alveolar echinococcosis.
PMID- 28416239
TI - Postprandial hypoglycemia as the only manifestation of insulinoma: exceptional
case report.
PMID- 28416240
TI - Efficacy of tumour necrosis factor antagonists in stricturing Crohn's disease: A
tertiary center real-life experience.
AB - BACKGROUND: Stenosis is the most common complication of Crohn's disease (CD).
Long-term outcome of patients receiving tumour necrosis factor (TNF) antagonists
for such disease complication is poorly understood. METHODS: 51 CD patients (from
July 2006 to November 2015) who had a diagnosis of small bowel or colonic
stenosis, diagnosed by colonoscopy and/or MRI enterography, and were treated with
TNF antagonists (adalimumab or infliximab) were enrolled. The primary outcome was
to assess the rate of success of TNF antagonists on avoiding abdominal surgery
for stricturing CD patients. RESULTS: 20 patients (39.2%) underwent surgery
during the follow-up period. The overall incidence of abdominal surgery was 1.8
per 100 person-months at risk, while the median time to surgery was 37.9 months.
The univariable and multivariable Cox's proportional hazards analysis of baseline
parameters indicated that disease location (colonic vs ileal, HR: 28.2, 95% CI:
2.45-324, p=0.007; ileocolonic vs ileal, HR: 3.38, 95% CI: 1.09-10.5, p=0.035),
prestenotic dilatation (per 1-mm increase, HR: 1.08, 95% CI: 1.01-1.15, p=0.022)
and the existence of non-perianal fistula (HR: 9.77, 95% CI: 2.99-31.9, p<0.001)
are independent risk factors for abdominal surgery. CONCLUSIONS: In stricturing
CD, anti-TNFs are effective in up to about two-thirds of the patients.
PMID- 28416241
TI - Circulating tumor DNA-From bench to bedside.
AB - In the era of personalized medicine, tumor sampling is paramount to enable the
assessment of actionable molecular aberrations to help rationalize and guide
treatment decisions. Longitudinal tracking of such aberrations may also be
helpful to detect emerging drug resistance and to allow for timely modifications
to ongoing therapies to improve patient outcomes. Nevertheless, tumor tissue
sampling involves an invasive procedure with potential risks to patients and
involves logistical challenges. As such, other less invasive and safer methods
such as blood sampling for molecular profiling has been gaining traction. In this
article, we discuss the concept of circulating tumor DNA, the technology
platforms available for its interrogation, and its current applications in the
clinic. We also envision how circulating tumor DNA may be applied at multiple
time points along a patient's cancer journey to guide diagnosis, prognostication,
and therapeutic decisions.
PMID- 28416242
TI - Human papillomavirus and oral squamous cell carcinoma: A review of HPV-positive
oral squamous cell carcinoma and possible strategies for future.
AB - Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Besides tobacco
use and alcohol consumption, human papillomavirus (HPV) infection has also been
identified as a risk factor for OSCC recently. The OSCC incidence has increased
in recent years, especially among younger women. The purpose of this article is
to review clinical and epidemiological studies on the association between HPV
infection and OSCCs, and the efficacy of HPV vaccine, so as to provide possible
policy implications for preventing HPV-positive OSCC. It is necessary to review
the present related body of knowledge to determine whether the association
between HPV infection and OSCC has been thoroughly studied. The study was based
on literature review. Studies were identified using electronic databases
including MEDLINE, PubMed, EMBASE, etc. The inclusion and exclusion criteria were
based on consultation from a panel of experts in this area and carefully
designed. Based on a systematic review of literatures, HPV infection is a
possible cause for the incidence of HPV-positive OSCCs. The prevalence of HPV
infection possibly contributed to the increasing trends of HPV-positive OSCCs.
Oral HPV infection is a form of HPV transmission. Oral sex behaviors and open
mouthed kissing are probably reasons for oral HPV infection. We also have some
epidemiological evidences proving that HPV vaccine provides a possible solution
for preventing oral HPV infection. Increased awareness of HPV-positive OSCCs is
essential due to the severity of this problem. Biological and epidemiological
data regarding the link between sexual behavior and HPV-associated cancers
indicate a probable connection, although definitive data are needed. Future
studies are needed to investigate the mechanisms of how HPV infection causes HPV
positive OSCCs, whether HPV vaccine provides a prevention for OSCCs, and other
important issues.
PMID- 28416243
TI - Psychological Interventions for Children with Functional Somatic Symptoms: A
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To analyze the effectiveness of psychological treatments on symptom
load and associated disability in children with functional somatic symptoms, and
to explore potential moderators of effects. STUDY DESIGN: Cochrane, PubMed,
PsycINFO, EMBASE, and CINAHL were searched for randomized controlled trials
published in peer-reviewed journals. Randomized controlled trials studying the
effect of a psychological treatment on symptom load and disability in children
with functional somatic symptoms were selected. Data on symptom load, disability,
and school absence directly post-treatment and at follow-up were extracted by 2
assessors. Studies were appraised with the Cochrane risk of bias tool.
Standardized mean differences were pooled in a random-effects model.
Heterogeneity in effect-sizes was explored by use of meta-regressions. PROSPERO
Registration ID: CRD42015029667. RESULTS: Out of 4098 identified records, 27
studies were included in this review of which 21 were included in meta-analyses.
Psychological treatments reduced symptom load (Hedges g = -0.61), disability
(Hedges g = -0.42), and school absence (Hedges g = -0.51) post-treatment in
children suffering from various functional somatic symptoms. Effects were
maintained at follow-up. Type and duration of symptoms, age, and treatment dose
did not explain heterogeneity in effect-sizes between studies. Effect-sizes
should be interpreted with caution because of the variety in outcome measures,
unexplained heterogeneity in found effects and potential publication bias.
CONCLUSIONS: Psychological interventions reduce symptom load, disability, and
school absence in children with functional somatic symptoms. Future research
should clarify which patient and treatment characteristics modify outcomes.
PMID- 28416244
TI - Response to comment on: Upper gastrointestinal endoscopy is safe and feasible in
the early postoperative period after Roux-en-Y gastric bypass.
PMID- 28416245
TI - A simple and efficient method for CRISPR/Cas9-induced mutant screening.
AB - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated protein 9 (Cas9) system provides a technological breakthrough in
mutant generation. Several methods such as the polymerase chain reaction
(PCR)/restriction enzyme (RE) assay, T7 endonuclease I (T7EI) assay, Surveyor
nuclease assay, PAGE-based genotyping assay, and high-resolution melting (HRM)
analysis-based assay have been developed for screening CRISPR/Cas9-induced
mutants. However, these methods are time- and labour-intensive and may also be
sequence-limited or require very expensive equipment. Here, we described a cost
effective and sensitive screening technique based on conventional PCR, annealing
at critical temperature PCR (ACT-PCR), for identifying mutants. ACT-PCR requires
only a single PCR step followed by agarose gel electrophoresis. We demonstrated
that ACT-PCR accurately distinguished CRISPR/Cas9-induced mutants from wild type
in both rice and zebrafish. Moreover, the method can be adapted for accurately
determining mutation frequency in cultured cells. The simplicity of ACT-PCR makes
it particularly suitable for rapid, large-scale screening of CRISPR/Cas9-induced
mutants in both plants and animals.
PMID- 28416246
TI - Leg movements during sleep and respiratory events are not causally linked.
PMID- 28416247
TI - Adaptive CRT in patients with normal AV conduction and left bundle branch block:
Does QRS duration matter?
AB - BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is a dynamic
optimization algorithm which paces only the left ventricle (LV) when atrio
ventricular (AV) conduction is normal, thus reducing right ventricular (RV)
pacing. However, the impact of QRS duration on aCRT efficacy remains uncertain.
We examined whether QRS duration impacts aCRT effectiveness in patients with left
bundle branch block (LBBB) and preserved AV conduction. METHODS: Randomized
patients in the Adaptive CRT trial, which enrolled NYHA III/IV patients, were
used in this analysis. Patients were randomized to receive aCRT or echo-optimized
bi-ventricular CRT (control arm). Endpoints for this analysis were clinical
composite score (CCS) at 6months post-implant and time to first heart failure
(HF) hospitalization or death. RESULTS: Among the 199 patients with LBBB and
normal AV intervals at baseline, 80 patients (40%) had a baseline moderately wide
QRS of 120-150ms. In this subgroup, a greater proportion of aCRT patients had an
improved CCS (79% vs. 50%) at 6months compared to the control group (p=0.03).
There was also a trend toward a lower risk of death or HF hospitalization (hazard
ratio: 0.53; 95% CI: 0.24-1.15; p=0.10) in the moderately wide QRS subgroup with
aCRT compared to the control arm. In the wide QRS subgroup, the efficacy was
comparable in both treatment arms. CONCLUSION: Adaptive CRT was associated with
improved patient outcomes over echo-optimized bi-ventricular CRT in patients with
preserved AV conduction, LBBB, and moderately wide QRS. The adaptive cardiac
resynchronization therapy trial (ClinicalTrials.gov Identifier: NCT00980057) was
sponsored by Medtronic plc, Mounds View, MN.
PMID- 28416249
TI - Prognostic accuracy of clinical signs and diagnostic tests in cow's milk allergy
in newborns.
AB - BACKGROUND: The aim of the study was to explore the correlation between clinical
signs and confirmatory tests for cow's milk allergy (CMA) in the neonatal period
and their relation to family history and the occurrence of food allergies in the
postneonatal period. METHODS: The medical documentation of 361 newborns with
suspected CMA and exclusion of other comorbidities was analyzed. The correlations
between clinical signs and methods to confirm CMA [elevated levels of total
immunoglobulin E (IgE) and/or specific IgE for cow's milk, improvement after the
introduction of a cow's milk-free diet and positive challenge procedure] were
studied. In 90 children, the data were additionally analyzed in relation to
outcome (at the age of 1-11 years), evaluated by questionnaires, which inquired
about signs and symptoms of food allergy, methods of CMA confirmation, and the
presence of other food allergies. RESULTS: There was a positive correlation
between exanthema and confirmed CMA in the neonatal period (R = 0.184; p =
<0.001; n = 361), and hematochezia and confirmed CMA in the neonatal (R = 0.203;
p < 0.001; n = 361) and postneonatal period (R = 0.215; p = 0.042; n = 90).
Additional food allergies in the postneonatal period were positively correlated
with neonatal CMA (R = 0.275; p = 0.009; n = 90). No correlation was found
between a positive family history of food allergies and CMA in the neonatal (R =
0.66; p = 0.398; n = 165) and postneonatal periods (R = 0.00; p = 1.000; n =
116). CONCLUSION: Neonatal exanthema and hematochezia were the predominant
clinical signs in neonates with CMA. Allergies to other food allergens appeared
more frequently in children with CMA in the neonatal period. Neonatal CMA did not
occur more frequently in families with food allergies.
PMID- 28416248
TI - Contemporary practice and outcomes of an elderly cohort of Japanese patients with
non-ST-elevation acute coronary syndrome in the era of routine early invasive
strategy.
AB - BACKGROUND: An early invasive strategy for patients with non-ST-segment elevation
acute coronary syndrome (NSTE-ACS) has been recommended. However, patients at
greater risk including the elderly are more often managed conservatively. We
aimed to elucidate contemporary practice and outcomes of patients with NSTE-ACS
who were referred to our hospital located in Kitakyushu City, one of the most
aging metropolises in Japan. METHODS: A total of 270 consecutive NSTE-ACS
patients hospitalized between January 2012 and December 2014 were retrospectively
studied. RESULTS: Median [interquartile range] age was 73 [64, 80]years. Coronary
angiography was performed in 264 (98%) patients. Importantly, 75% and 89%
underwent angiography within 24h and 72h after admission, respectively.
Revascularization was done in 124 (79%). The all-cause, in-hospital mortality was
3.7% and was higher in patients aged >=80years (8.5% vs. 2.0% in those aged
<80years, p<0.0001). No patient developed major bleeding or stroke during
hospitalization. Killip class IV at presentation (odds ratio [OR] 8.77, 95%
confidence intervals [CI] 1.64-47.6) and left main trunk disease (OR 7.58, 95% CI
1.28-45.5) were independently associated with in-hospital death. These two
variables and a high (>=140) GRACE score were associated with a higher 1-year
mortality by Kaplan-Meier survival analysis (p<0.0001). CONCLUSIONS: An early
invasive strategy was safely done in an elderly cohort of Japanese patients with
NSTE-ACS. In addition to early invasive approach, a further therapeutic strategy,
most probably targeting a shock status, is needed to improve both short- and long
term survival.
PMID- 28416250
TI - Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy.
AB - Therapeutic hypothermia (TH) is a recommended regimen for newborn infants who are
at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy
(HIE). The Task Force of the Taiwan Child Neurology Society and the Taiwan
Society of Neonatology held a joint meeting in 2015 to establish recommendations
for using TH on newborn patients with HIE. Based on current evidence and experts'
experiences, this review article summarizes the key points and recommendations
regarding TH for newborns with HIE, including: (1) selection criteria for TH; (2)
choices of method and equipment for TH; (3) TH prior to and during transport; (4)
methods for temperature maintenance, monitoring, and rewarming; (5) systemic care
of patients during TH, including the care of respiratory and cardiovascular
systems, management of fluids, electrolytes, and nutrition, as well as sedation
and drug metabolism; (6) monitoring and management of seizures; (7) neuroimaging,
prognostic factors, and outcomes; and (8) adjuvant therapy for TH.
PMID- 28416251
TI - Initial Asthma Severity Assessment Tools as Predictors of Hospitalization.
AB - BACKGROUND: Assessment tools to classify and prioritize patients, such as systems
of triage, and indicators of severity, such as clinical respiratory scores, are
helpful in guiding the flow of asthmatic patients in the emergency department.
OBJECTIVE: Our aim was to assess the performance of the Pediatric Assessment
Triangle (PAT), triage level (TL), Pulmonary Score (PS), and initial O2
saturation (O2 sat), in predicting hospitalization in pediatric acute asthma
exacerbations. STUDY DESIGN: Retrospective study evaluating PAT, TL, and PS at
presentation, and initial O2 sat of asthmatic children in the pediatric emergency
department (PED). The primary outcome measure was the rate of hospitalization.
Secondary outcomes were length of stay (LOS) in the PED and admission to the
pediatric intensive care unit (PICU). RESULTS: PAT, TL, PS, and initial O2 sat
were recorded in 14,953 asthmatic children. Multivariate analysis yielded the
following results: Abnormal PAT and more severe TLs (I-II) were independent risk
factors for hospitalization (odds ratio [OR] 1.6, 95% confidence interval [CI]
1.4-1.8; OR 3.4, 95% CI 2.6-4.3, respectively) and longer LOS (OR 1.5, 95% CI 1.3
1.7; OR 2.6, 95% CI 2-3.3, respectively). PS > 3 showed a strong association with
hospitalization (OR 8.1, 95% CI 7-9.4), PICU admission (OR 9.6, 95% CI 3-30.9)
and longer LOS (OR 6.2, 95% CI 5.6-6.9). O2 sat < 94% was an independent
predictor of admission (OR 5.2, 95% CI 4.6-5.9), PICU admission (OR 4.6, 95% CI
4.5-4.6), and longer LOS (OR 4.6, 95% CI 4.1-5.2). CONCLUSIONS: PAT, TL, PS, and
initial O2 sat are good predictors of hospitalization in pediatric acute asthma
exacerbations.
PMID- 28416252
TI - Hydroceles-Not Just For Men.
AB - BACKGROUND: Hydroceles develop in females through the canal of Nuck. This canal
is formed when the processes vaginalis fails to obliterate during development.
The canal of Nuck can lead to the formation of not only hydroceles, but hernias
as well. Although physicians typically think of hydroceles occurring in males, on
rare occasions, they do occur in females because of this defect. They are often
mistaken for incarcerated hernias, making ultrasound an excellent tool to
distinguish between them and guide further treatment. CASE REPORT: We report a
rare case of a 46-year-old female with the chief complaint of a painful groin
mass. A diagnosis of a hydrocele was made by point of care ultrasonography in the
emergency department after being misdiagnosed by computed tomography scan on two
previous occasions. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Point of
care ultrasound (POCUS) is a valuable tool for emergency physicians and can lead
to quick diagnoses and appropriate management of the patient. Using ultrasound in
conjunction with other imaging modalities can improve diagnostic accuracy. POCUS
is portable and a powerful tool for immediate answers, and continues to prove its
utility for clinical decision making.
PMID- 28416253
TI - Mechanical Stability of the Taper Connection of Large Metal Femoral Heads With
Adapter Sleeves in Total Hip Arthroplasty Analyzed Using Explicit Finite Element
Simulations.
AB - BACKGROUND: Large diameter heads (LDHs) of metal-on-metal bearings in total hip
arthroplasty provide increased range of motion and reduced dislocation rates.
However, major concerns grew over high wear rates from the modular connection
between femoral stem and head, especially in combination with adapter sleeves.
METHODS: A computational study on the taper connection stability of LDH (50 mm)
with adapter sleeves of different lengths (S, M, L, and XL) compared with a
standard femoral head (32 mm) without adapter sleeves was conducted using
explicit finite element analyses. Four different impact configurations were
considered resulting from varied mallet mass (0.5 vs 1.0 kg) and velocity (1.0 vs
2.0 m/s). The taper stability was evaluated by determination of the pull-off
forces and micromotions due to simulated joint loads during walking (2 kN and 7.9
Nm, respectively). Moreover, the deformations of the adapter sleeves and the
contact area in the taper connections were evaluated. RESULTS: Although the pull
off forces of the LDH with different-sized adapter sleeves were comparable,
contact area decreased and adapter sleeve deformations increased (up to 283%)
with an increasing adapter sleeve length. Moreover, the micromotions of LDH with
adapter sleeves were up to 7-times higher, as compared with the standard femoral
head without an adapter sleeve. CONCLUSION: The present numerical study confirms
that the assembly technique of LDH with adapter sleeves reveals increased
micromotions compared with standard femoral head sizes. We could demonstrate that
deviations of the stem trunnion geometry and improper surgical instructions led
to worse mechanical stability of the taper connection.
PMID- 28416254
TI - Non-critical urinary cadmium excretion as a risk factor associated with tubular
markers of early kidney injury in Central Mexico.
PMID- 28416255
TI - Differences between 2nd and 3rd generation seric parathormone determination
methods on mortality in haemodialysis patients.
AB - : Parathormone plays a key role in controlling mineral metabolism. PTH is
considered a uremic toxin causing cardiovascular damage and cardiovascular
mortality in dialysis patients. There are two different assays to measure PTH
called 2nd generation or intact PTH (iPTH) and 3rd generation or bioPTH (PTHbio).
OBJECTIVE: To evaluate the differences in mortality of dialysis patients between
both assays to measure PTH, as well as the possible prognostic role of the
PTHbio/iPTH ratio. METHODS: 145 haemodialysis patients were included with 2-year
monitoring including baseline laboratory test and annually thereafter. RESULTS:
21 patients died in the first year and 28 in the second. No correlation was found
between PTH, PTHbio and PTHbio/iPTH ratio with mortality. Both PTH have a perfect
correlation between them and correlate similarly with other molecules of the
mineral metabolism. The extreme baseline values of PTH are those of higher
mortality. In survival by iPTH intervals (according to guidelines and COSMOS
study), a J curve is observed. When iPTH increases, the ratio decreases, possibly
when increasing fragments no. 1-84. There is no greater prognostic approximation
on mortality with PTHbio than PTHi. There was also no difference in mortality
when progression ratio PTHbio/PTHi was analysed. CONCLUSIONS: We didn't find any
advantages to using bioPTH vs. PTHi as a marker of mortality. BioPTH limits of
normality must be reevaluated because its relationship with iPTH is not
consistent. Not knowing these limits affects its prognostic value.
PMID- 28416256
TI - Youth psychological distress and intermediary markers of risk for CVD: The
emerging field of pediatric psychocardiology.
PMID- 28416257
TI - Nrf2 and regulation of the antioxidant system in the Antarctic silverfish,
Pleuragramma antarctica: Adaptation to environmental changes of pro-oxidant
pressure.
AB - Despite the key importance of Nrf2-Keap1 in regulating antioxidant system in
vertebrates, this system is still poorly investigated in marine species. The
present study focused on the Antarctic silverfish Pleuragramma antarctica which,
during the final phases of embryo development in platelet ice, is challenged by a
sudden enhancement of environmental oxidative conditions associated to ice
melting. Partial coding sequences were identified for Nrf2, its repressor Keap1
and for typical Nrf2-target antioxidant genes, like catalase, glutathione
peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase. Compared to
temperate homologues, the protein sequences showed an elevated conservation of
amino acids essential for catalytic functions, while a few specific substitutions
in non-essential regions may represent a molecular adaptation to improve
flexibility and accessibility to active site at cold temperatures. The role of
the Nrf2-Keap1 pathway in modulating the activation of antioxidant defences was
demonstrated at both transcriptional and functional levels with a clear temporal
increase of antioxidant protection in embryos before the hatching. Such findings
confirm the importance of Nrf2 and highlight regulation of antioxidants as an
adaptive strategy in P. antarctica to protect the early life stages toward the
environmental changes of pro-oxidant pressure.
PMID- 28416258
TI - [Description of 3 cases of skin and soft tissue infections caused by
Streptococcus pneumoniae].
AB - The role of Streptococcus pneumoniae as a causative agent of skin and soft tissue
infections (SSTI) is unusual and its clinical interpretation is difficult. We
describe here three cases of SSTI due to S. pneumoniae in patients admitted to
the Provincial Pediatric Hospital of Misiones, Argentina that were detected
during 10 years of invasive disease (ID) surveillance documented in 2010, 2011
and 2015. These cases involved two girls aged 8 and 7 months old, and a two-year
old male child with diagnoses of gluteal abscess, preseptal cellulites and
pyoderma respectively. All the patients were eutrophic and in good general
condition on admission; one of them was seropositive for HIV. Antimicrobial
susceptibility and serotypes were framed within the local epidemiology of
invasive pneumococcal disease. Despite its low frequency, S. pneumoniae as an
etiological agent of SSTI must be considered. Our findings revalue the role of
the diagnostic laboratory and contribute to document the behavior of this
pathogen.
PMID- 28416259
TI - Parenteral glutamine should not be routinely used in adult critically ill
patients.
PMID- 28416260
TI - Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated With
Dose-escalated Image-guided Intensity-modulated Radiotherapy.
AB - AIMS: To quantify and qualify late genitourinary toxicity in a cohort of patients
with localised prostate cancer treated with image-guided intensity-modulated
radiotherapy (IMRT) to doses >=78 Gy. MATERIALS AND METHODS: The cohort consisted
of 300 patients treated with definitive dose-escalated IMRT between 2007 and
2013. Ninety-seven patients received 78-80 Gy in 38 fractions, and 203 received
82-84 Gy in 40 fractions. International Prostate Symptoms Score (IPSS) and
supplemental quality of life data were recorded at baseline, weekly during
treatment and at follow-up. Genitourinary toxicities were recorded using modified
Radiation Therapy Oncology Group criteria during weekly treatment review and at
each follow-up. Kaplan-Meier curves were used to assess the cumulative incidence
of grade >= 2 genitourinary toxicity at 3 years. Baseline patient characteristics
and symptoms were then used in univariate and multivariate analyses to identify
predictors of late urinary toxicity. RESULTS: The median follow-up was 58 months
(range 9-109 months). The actuarial cumulative 3 year rates of grade >= 2 and
grade 3 genitourinary toxicity were 14.9% and 2.8%, respectively. There was no
grade 4 toxicity. History of transurethral resection of the prostate (TURP),
alpha blocker use before radiation, any hormone use, baseline IPSS >= 14 and pre
existing incontinence or nocturia were significantly associated with late >= 2
genitourinary toxicity on univariate analysis. On multivariate analysis, only
previous TURP retained significance, with a hazard ratio of 2.54 (P=0.002).
CONCLUSION: Our study showed acceptable levels of late grade 2 genitourinary
toxicity and low rates of late grade 3 genitourinary toxicity in a cohort of
patients with prostate cancer treated with image-guided IMRT to doses between 78
and 84 Gy. Variables associated with increased late >= 2 genitourinary toxicity
include previous TURP, alpha blocker use, hormone use and pre-existing urinary
dysfunction.
PMID- 28416262
TI - Use of dilute ammonia gas for treatment of 1,2,3-trichloropropane and explosives
contaminated soils.
AB - Laboratory studies were performed to test a novel reactive gas process for in
situ treatment of soils containing halogenated propanes or explosives. A soil
column study, using a 5% ammonia-in-air mixture, established that the treatment
process can increase soil pH from 7.5 to 10.2. Batch reactor experiments were
performed to demonstrate contaminant destruction in sealed jars exposed to
ammonia. Comparison of results from batch reactors that were, and were not,
exposed to ammonia demonstrated reductions in concentrations of 1,2,3
trichloropropane (TCP), 1,3-dichloropropane (1,3-DCP), 1,2-dicholoropropane (1,2
DCP) and dibromochloropropane (DBCP) that ranged from 34 to 94%. Decreases in TCP
concentrations at 23 degrees C ranged from 37 to 65%, versus 89-94% at 62
degrees C. A spiked soil column study was also performed using the same set of
contaminants. The study showed a pH penetration distance of 30 cm in a 2.5 cm
diameter soil column (with a pH increase from 8 to > 10), due to treatment via 5%
ammonia gas at 1 standard cubic centimeter per minute (sccm) for 7 days. Batch
reactor tests using explosives contaminated soils exhibited a 97% decrease in
2,4,6-trinitrotoluene (TNT), an 83% decrease in nitrobenzene, and a 6% decrease
in hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). A biotransformation study was
also performed to investigate whether growth of ammonia-oxidizing microorganisms
could be stimulated via prolonged exposure of soil to ammonia. Over the course of
the 283 day study, only a very small amount of nitrite generation was observed;
indicating very limited ammonia monooxygenase activity. Overall, the data
indicate that ammonia gas addition can be a viable approach for treating
halogenated propanes and some types of explosives in soils.
PMID- 28416263
TI - The keys to conservative treatment of early-stage squamous cell carcinoma of the
tonsillar region.
AB - To analyze the medical literature devoted to work-up, epidemiology, local
control, survival, complications and sequelae after conservative treatment for
early-stage squamous cell carcinoma of the tonsillar region. An analysis of the
PubMed (1975-2016) database was performed using the following keywords and
associations: "tonsil/tonsillar region/oropharynx" AND "squamous cell carcinoma"
AND "early-stage (I-II; T1-2N0M0)" AND "radiation therapy/radiotherapy" OR
"conservative surgery/oropharyngectomy/transoral surgery/radical tonsillectomy".
The search retrieved 10 retrospective series documenting local control and/or
survival in series with more than 50 cases and a minimum 2 years' follow-up after
conservative treatment; no prospective studies, meta-analyses and/or Cochrane
analyses were found. Magnetic resonance imaging is the key radiological exam for
local extension assessment. Human papilloma virus infection (HPV) is a risk
factor that must be screened for systematically, since it induces tumoral radio
sensitivity and increases the risk of specific synchronous and metachronous
second primaries. Whatever conservative treatment used, local control and
survival rates higher than 85% were achieved. Implementing intensity-modulated
radiation therapy reduced the incidence and severity of radiation-related
complications and sequelae. Transoral surgery yielded very low
morbidity/mortality rates, enabled association to ipsilateral neck dissection,
and allowed radiation therapy to be reserved for the management of metachronous
second primaries. Transoral surgery appeared to be the first-line option in the
majority of cases. Lifetime follow-up adapted to HPV status is mandatory. The
development of HPV vaccination does not mean that campaigns against smoking and
alcohol abuse are of diminished importance.
PMID- 28416261
TI - Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell
Lung Cancer.
AB - INTRODUCTION: The prognosis of patients with small cell lung cancer (SCLC)
remains very poor. Therefore, the development of new therapeutic approaches,
including immunotherapies, is desirable. PATIENTS AND METHODS: We conducted a
phase II study of personalized peptide vaccination (PPV), in which a maximum of 4
human leukocyte antigen-matched peptides were selected from 31 pooled peptides
according to the pre-existing peptide-specific IgG responses before vaccination.
The PPV was subcutaneously administered. RESULTS: Forty-six patients were
enrolled (median age, 63 years; 40 patients were men). Grade 1 (n = 13), 2 (n =
10), or 3 (n = 1) skin reactions at the injection sites were observed; however,
no other severe adverse events related to the PPV were observed. The median
survival time was 466, 397, 401, and 107 days in the subgroups with 0 (n = 5), 1
(n = 15), 2 (n = 12), and >= 3 (n = 14) previous chemotherapy regimens,
respectively. Peptide-specific IgG responses to the vaccinated peptides were
augmented in 70% and 95% of patients after 1 and 2 vaccination cycles,
respectively. The overall survival (OS) of patients with augmented IgG responses
to a greater number of nonvaccinated peptides after the second cycle of
vaccination was significantly longer (median survival time, 1237 days vs. 382
days; P = .010). In addition, augmentation of IgG responses specific to 6
peptides, including Lck-derived peptides, was significantly related to better OS
(P < .05, in each peptide). CONCLUSION: These results suggest the feasibility of
PPV for SCLC patients from the viewpoints of safety, immune boosting, and
possible prolongation of OS. Therefore, further evaluation of PPV for advanced
SCLC in prospective randomized trials is warranted.
PMID- 28416264
TI - Editor's Choice - Inequalities in Abdominal Aortic Aneurysm Screening in England:
Effects of Social Deprivation and Ethnicity.
AB - OBJECTIVE: Population screening for abdominal aortic aneurysm (AAA) in men is
currently ongoing in several countries. The aim was to examine the effects of
deprivation and ethnicity on uptake of screening for abdominal aortic aneurysm
(AAA) and prevalence of AAA. METHODS: This was a review of outcomes from a
population screening programme using data collected contemporaneously on a
bespoke national database. Men aged 65 in two annual cohorts (2013/14 and
2014/15) were invited for AAA screening. Attendance and prevalence of AAA (aortic
diameter >2.9 cm) were recorded. Results were compared according to measures of
social deprivation and recorded ethnicity. RESULTS: Some 593,032 men were invited
and 461,898 attended for ultrasound screening; uptake 77.9%. Uptake was related
to social deprivation: 65.1% in the most deprived decile, 84.1% in the least
deprived: OR for least deprived 2.84, 95% CI 2.76-2.92, p<.0001. Men in deprived
areas were more likely to actively decline screening: 6% versus 3.8% in the least
deprived decile. AAA were twice as common in the most deprived compared with the
least deprived decile: OR 2.1, 95% CI 1.77-2.27, p<.0001. AAA were more common in
white British men than in black (OR 0.46, 95% CI 0.31-0.71) or Asian (OR 0.18,
95% CI 0.13-0.26) men. There was considerable local variation in all findings.
CONCLUSIONS: Social deprivation affects uptake of AAA screening in 65 year old
men. Local factors are the most important determinants of uptake, so solutions to
improve uptake must be designed at local, not national level.
PMID- 28416265
TI - Comparison of outcomes for pediatric paraphimosis reduction using topical
anesthetic versus intravenous procedural sedation.
AB - BACKGROUND: Paraphimosis is an acute urologic emergency requiring urgent manual
reduction, frequently necessitating procedural sedation (PS) in the pediatric
population. The present study sought to compare outcomes among pediatric patients
undergoing paraphimosis reduction using a novel topical anesthetic (TA) technique
versus PS. METHODS: We performed a retrospective analysis of all patients
<18years old, presenting to a tertiary pediatric ED requiring analgesia for
paraphimosis reduction between October 2013 and September 2016. The primary
outcome was reduction first attempt success; secondary outcomes included
Emergency Department length of stay (ED LOS), adverse events and return visits.
Dichotomous outcomes were analyzed by Chi-square testing and multivariate linear
regression was used to compare continuous variables. RESULTS: Forty-six patients
were included; 35 underwent reduction using TA, 11 by PS. Patient age and
duration of paraphimosis at ED presentation did not differ between groups. There
was no difference in first attempt success between TA (32/35, 91.4%) and PS
groups (9/11, 81.8%; p=0.37). Mean ED LOS was 209min shorter for TA patients
(148min vs. 357min, p=0.001) and remained significantly shorter after controlling
for age and duration of paraphimosis (adjusted mean difference -198min, p=0.003).
There were no return visits or major adverse events in either group, however,
among successful reduction attempts, PS patients more frequently experienced
minor adverse events (7/9 vs. 0/32, p<0.001). CONCLUSIONS: Paraphimosis reduction
using TA was safe and effective. Compared to PS, TA was associated with a reduced
ED LOS and fewer adverse events. TA could potentially allow more timely reduction
with improved patient experience and resource utilization.
PMID- 28416266
TI - Removing default dispense quantity from opioid prescriptions in the electronic
medical record.
PMID- 28416267
TI - Molecular Mechanisms and Targets of Therapy for Hepatocellular Carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC
develops through a multistep process that involves the local tumor
microenvironment, intracellular signaling pathways, and altered metabolic system
that allows the cancer proliferation. Understanding the mechanisms of tumor
development and progression is critical to developing improved therapies aimed at
better survival. This article reviews the molecular mechanisms of HCC development
and highlights the potential therapeutic targets for treatments.
PMID- 28416268
TI - Post-traumatic Stress Disorder and Risk of Parkinson Disease: A Nationwide
Longitudinal Study.
AB - OBJECTIVE: Increasing evidence has suggested a relationship between post
traumatic stress disorder (PTSD) and neurodegenerative disorder, such as
Alzheimer disease. The association between PTSD and Parkinson disease (PD),
however, remains unclear. METHOD: Using the Taiwan National Health Insurance
Research Database, 7,280 subjects (1,456 patients aged >=45 years with PTSD and
5,824 age-/sex-matched individuals without PTSD) were enrolled between 2002 and
2009 and followed to the end of 2011. Subjects who developed PD during the follow
up period were identified. RESULTS: An increased risk of developing PD was found
in patients with PTSD (Wald chi2 = 12.061, hazard ratio [HR]: 3.46, 95%
confidence interval [CI]: 1.72-6.96) compared with individuals without PTSD,
after adjusting for demographic data and medical and psychiatric comorbidities.
The sensitivity tests after excluding the first year observation (Wald chi2 =
7.948, HR: 3.01, 95% CI: 1.40-6.46) and the first 3-year observation (Wald chi2 =
5.099, HR: 3.07, 95% CI: 1.16-8.15) were consistent. CONCLUSIONS: Patients with
PTSD had an elevated risk of developing PD in later life. Further studies would
be required to clarify the exact pathophysiology between PTSD and PD and to
investigate whether the prompt intervention for PTSD may reduce this risk.
PMID- 28416269
TI - DNA-Protein Crosslink Proteolysis Repair.
AB - Proteins that are covalently bound to DNA constitute a specific type of DNA
lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles
to the progression of DNA replication. If not repaired, DPCs cause stalling of
DNA replication forks that consequently leads to DNA double-strand breaks, the
most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of
DPC repair was unclear until now. Recent work unveiled that DPC repair is
orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN
in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two
proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis
repair as a separate DNA repair pathway for genome stability and protection from
accelerated aging and cancer.
PMID- 28416270
TI - Plasma levels and leucocyte RNA expression of adipokines in young patients with
coronary artery disease, in metabolic syndrome and healthy controls.
AB - OBJECTIVES: Little is known about the role of adipokines in the pathogenesis of
coronary artery disease in young patients. The aims of this study were to compare
serum levels of adipokines and expression of adipokines in peripheral blood
leukocytes in patients with premature coronary artery disease (CAD), metabolic
syndrome and healthy individuals. DESIGN AND METHODS: Sixty-five patients with
premature CAD (men 18-45years old and women 18-55years old) formed the study
group. The control groups were 75 patients with metabolic syndrome and 50 healthy
individuals. For each group, RNA expression in peripheral blood leukocytes was
determined for 24 different adipokines and 11 adipokines were examined in serum.
RESULTS: In individuals with CAD, serum visfatin levels were significantly higher
than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7ug/L,
P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3ug/L, P<0.001) and ZAG2
(45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating
curve (ROC) analysis for testing the validity of these adipokines in the
diagnosis of CAD compared to control groups provided the following areas under
the curve (AUC): omentin-1 AUC 0.97 (cut-off <=222ug/L), ZAG2 AUC 0.89 (cut-off
<=51.7mg/L) and visfatin AUC 0.74 (cut-off >=1.0ug/L) (P<0.001 in all cases).
Visfatin and omentin-1 serum levels did not differ between the acute phase of
myocardial infarction and the chronic phase of CAD. In patients with CAD, we
found no significant relation between mRNA expression and adipokine
concentration. CONCLUSION: Serum omentin-1, visfatin and ZAG2 could serve as
biomarkers of premature CAD in young apparently healthy people.
PMID- 28416271
TI - The challenge of criteria for interstitial pneumonia with autoimmune features.
PMID- 28416272
TI - Biocidal effects of Piper hispidinervum (Piperaceae) essential oil and synergism
among its main components.
AB - In this study we evaluated the effect of a pressure gradient (1-2 atm) in the
extraction and composition of the essential oil (EO) of Piper hispidinervum by
steam distillation. We also evaluated the insect antifeedant effects (Spodoptera
littoralis, Leptinotarsa decemlineata, Myzus persicae and Rhopalosiphum padi) and
nematicidal activity (Meloidogyne javanica) of the oils, their major components
and their synergistic interactions. Safrole was the major component (78-81%)
followed by terpinolene (5-9%). The EOs tested were effective insect
antifeedants. Safrole, explained most of the insect antifeedant action of P.
hispidinervum EOs. When safrole and terpinolene were tested in binary
combinations, low ratios of safrole improved the antifeedant effects of
terpinolene. P. hispidinervum EOs caused higher mortality of M. javanica
juveniles than their major components. In binary combinations, low ratios of
terpinolene increased the nematicidal effects of safrole. The EO treatment
strongly suppressed nematode egg hatching and juvenile infectivity. P.
hispidinervum EOs affected the germination of S. lycopersicum and L. sativa
mostly at 24 h of treatment, being L. sativa the most sensitive. Safrole
moderately affected germination and root growth of L. sativa, S. lycopersicum and
L. perenne. Terpinolene only affected S. lycopersicum root growth.
PMID- 28416273
TI - Attention allocation and social worries predict interpretations of peer-related
social cues in adolescents.
AB - Adolescence is a sensitive period for increases in normative but also
debilitating social fears and worries. As the interpretation of interpersonal
cues is pertinent to social anxiety, investigating mechanisms that may underlie
biases in social cue appraisal is important. Fifty-one adolescents from the
community aged 14-19 were presented with self- and other-relevant naturalistic
social scenes for 5s and then required to rate either a negative or a positive
interpretation of the scene. Eye-tracking data were collected during the free
viewing period to index attentional deployment. Individual differences in social
worries were measured via self-report. Social anxiety levels significantly
predicted biases in interpretation ratings across scenes. Additionally,
cumulative attentional deployment to peer cues also predicted these
interpretation biases: participants who spent more time on facial displays
perceived more threat, i.e. endorsed more negative and less positive
interpretations. Self-relevant scenes yielded greater tendencies to draw negative
interpretations. Finally, older adolescents also selected more benign
interpretations. Social anxiety is associated with a bias in interpreting social
cues; a cognitive bias that is also influenced by attentional deployment. This
study contributes to our understanding of the possible attention mechanisms that
shape cognitions relevant to social anxiety in this at-risk age group.
PMID- 28416274
TI - Fatigue in multiple sclerosis - Insights into evaluation and management.
AB - Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease
of the central nervous system, characterized by the accumulation of numerous
neurological symptoms and signs throughout its course. Fatigue is one of the most
distressing complaints that MS patients may experience over their lifetime. In
spite of its high prevalence, the pathophysiology of MS fatigue is far from being
fully elucidated and a constellation of mechanisms seems implicated in this
setting. Several factors could contribute to its development and/or exacerbation,
and this requires a careful workup in order to search for all possible underlying
causes, such as sleep disturbances, endocrine dysfunction and mood disorders, to
cite a few. The aim of this review is to revisit the definition of MS fatigue,
provide an overview of its pathophysiology, and reappraise its clinical,
structural and functional correlates. Additionally, we discuss the available
assessment tools, as well as the various management strategies including
pharmacological and non-pharmacological interventions. Special emphasis will be
placed on the role of noninvasive brain stimulation techniques in this field.
Finally, we propose a "road map" to facilitate the diagnosis and guide the
therapeutic regimens of this multifactorial and multidimensional construct.
PMID- 28416275
TI - Cisplatin Analogs Confer Protection against Cyanide Poisoning.
AB - Cisplatin holds an illustrious position in the history of chemistry most notably
for its role in the virtual cure of testicular cancer. Here we describe a role
for this small molecule in cyanide detoxification in vivo. Cyanide kills
organisms as diverse as insects, fish, and humans within seconds to hours.
Current antidotes exhibit limited efficacy and are not amenable to mass
distribution requiring the development of new classes of antidotes. The binding
affinity of the cyanide anion for the positively charged metal platinum is known
to create an extremely stable complex in vitro. We therefore screened a panel of
diverse cisplatin analogs and identified compounds that conferred protection from
cyanide poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery
pipeline begins to establish the characteristics of platinum ligands that
influence their solubility, toxicity, and efficacy, and provides proof of concept
that platinum-based complexes are effective antidotes for cyanide poisoning.
PMID- 28416276
TI - Synthesis and Degradation of Adenosine 5'-Tetraphosphate by Nicotinamide and
Nicotinate Phosphoribosyltransferases.
AB - Adenosine 5'-tetraphosphate (Ap4) is a ubiquitous metabolite involved in cell
signaling in mammals. Its full physiological significance remains unknown. Here
we show that two enzymes committed to NAD biosynthesis, nicotinamide
phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase
(NAPT), can both catalyze the synthesis and degradation of Ap4 through their
facultative ATPase activity. We propose a mechanism for this unforeseen
additional reaction, and demonstrate its evolutionary conservation in bacterial
orthologs of mammalian NAMPT and NAPT. Furthermore, evolutionary distant forms of
NAMPT were inhibited in vitro by the FK866 drug but, remarkably, it does not
block synthesis of Ap4. In fact, FK866-treated murine cells showed decreased NAD
but increased Ap4 levels. Finally, murine cells and plasma with engineered or
naturally fluctuating NAMPT levels showed matching Ap4 fluctuations. These
results suggest a role of Ap4 in the actions of NAMPT, and prompt to evaluate the
role of Ap4 production in the actions of NAMPT inhibitors.
PMID- 28416277
TI - Radiology Education: It Takes a Village!
PMID- 28416278
TI - AI-2 quorum sensing negatively regulates rbf expression and biofilm formation in
Staphylococcus aureus.
AB - Staphylococcus aureus is an important pathogen that is capable of forming
biofilms on biomaterial surfaces to cause biofilm-associated infections.
Autoinducer 2 (AI-2), a universal language for interspecies communication, is
involved in a variety of physiological activities, although its exact role in
Gram-positive bacteria, especially in S. aureus, is not yet thoroughly
characterized. Herein we demonstrate that inactivation of luxS, which encodes AI
2 synthase, resulted in increased biofilm formation and higher polysaccharide
intercellular adhesion (PIA) production compared with the wild-type strain in S.
aureus NCTC8325. The transcript level of rbf, a positive regulator of biofilm
formation, was significantly increased in the luxS mutant. All of the parental
phenotypes could be restored by genetic complementation and chemically
synthesized 4,5-dihydroxy-2,3-pentanedione, the AI-2 precursor molecule,
suggesting that AI-2 has a signaling function to regulate rbf transcription and
biofilm formation in S. aureus. Phenotypic analysis revealed that the luxS rbf
double mutant produced approximately the same amount of biofilms and PIA as the
rbf mutant. In addition, real-time quantitative reverse transcription-PCR
analysis showed that the icaA transcript level of the rbf mutant was similar to
that of the luxS rbf double mutant. These findings demonstrate that the LuxS/AI-2
system regulates PIA-dependent biofilm formation via repression of rbf expression
in S. aureus. Furthermore, we demonstrated that Rbf could bind to the sarX and
rbf promoters to upregulate their expression.
PMID- 28416279
TI - The impact of work-life balance on intention to stay in academia: Results from a
national survey of pharmacy faculty.
AB - PURPOSE: Border-Crossing theory suggests work-life balance and career
satisfaction are inter-related and disappointment in work-life balance may
predict changes in one's career path. Application of this theory to health
profession faculty is plausible but has not been fully explored. The purpose of
this study is to examine factors related to reported career change intention
among United States pharmacy school faculty and to determine if Border-Crossing
theory fits these observations. METHODS: Results from a national web-based survey
administered via Qualtrics(r) to American Association of Colleges of Pharmacy
(AACP) members were utilized. Bivariate analyses were conducted to compare
differences among faculty stating an intention to stay or leave academia. A
logistic multivariate model was used to determine if work-life balance remains
significant when controlling for other variables and if survey results support
the Border-Crossing theory. RESULTS: Nearly all (seven hundred of 811 responders,
or 86.3%) stated a desire to stay in academia. Faculty with higher work-life
balance were more likely to report an intent to remain in academia. Male, older,
full-professor and non-pharmacy practice faculty (social or administrative
science, pharmacology, medicinal chemistry and others) were more likely to state
an intention to remain in academia relative to their counterparts. Lower stress,
as measured by the validated Perceived Stress Scale (PSS) scores, was seen among
faculty stating a desire to remain in academia. Work-life balance remained
significantly inversely related to career change intention after controlling for
all other factors. CONCLUSION: A significant factor related to pharmacy faculty's
stated intention to remain in academia was work-life balance. Other factors such
as gender, age, rank, stress level and department may also play a role. These
results support the application of the Border-Crossing theory in health
profession faculty and may provide pharmacy school administrators and
stakeholders with insight to foster faculty retention and decrease faculty
turnover.
PMID- 28416280
TI - Progress toward Gene Therapy for Duchenne Muscular Dystrophy.
AB - Duchenne muscular dystrophy (DMD) has been a major target for gene therapy
development for nearly 30 years. DMD is among the most common genetic diseases,
and isolation of the defective gene (DMD, or dystrophin) was a landmark
discovery, as it was the first time a human disease gene had been cloned without
knowledge of the protein product. Despite tremendous obstacles, including the
enormous size of the gene and the large volume of muscle tissue in the human
body, efforts to devise a treatment based on gene replacement have advanced
steadily through the combined efforts of dozens of labs and patient advocacy
groups. Progress in the development of DMD gene therapy has been well documented
in Molecular Therapy over the past 20 years and will be reviewed here to
highlight prospects for success in the imminent human clinical trials planned by
several groups.
PMID- 28416281
TI - Population structure of Han nationality in Central-Southern China.
AB - Knowledge of population structure is very important for forensic genetics.
However, the population substructure in Central-Southern China Han nationality
has still not been fully described. In this study, we investigated the genetic
diversity of 15 forensic autosomal STR loci from 6879 individuals in 12 Han
populations subdivided by administrative provinces in Central-Southern China. The
statistical analysis of genetic variation showed that genetic differentiation
among these populations was very small with a Fst value of 0.0009. The
Discriminant Analysis of Principal Components (DAPC) showed that there were no
obvious population clusters in Central-Southern China Han population. In
practice, the population structure effect in Central-Southern China Han
population can be negligible in forensic identification and paternity testing.
PMID- 28416282
TI - Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells.
AB - Research on human brain development and neurological diseases is limited by the
lack of advanced experimental in vitro models that truly recapitulate the
complexity of the human brain. Here, we describe a robust human brain organoid
system that is highly specific to the midbrain derived from regionally patterned
neuroepithelial stem cells. These human midbrain organoids contain spatially
organized groups of dopaminergic neurons, which make them an attractive model for
the study of Parkinson's disease. Midbrain organoids are characterized in detail
for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we
show the presence of synaptic connections and electrophysiological activity. The
complexity of this model is further highlighted by the myelination of neurites.
The present midbrain organoid system has the potential to be used for advanced in
vitro disease modeling and therapy development.
PMID- 28416283
TI - Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with
Metabolic Disease.
AB - The striking rise of obesity-related metabolic disorders has focused attention on
adipocytes as critical mediators of disease phenotypes. To better understand the
role played by excess adipose in metabolic dysfunction it is crucial to decipher
the transcriptional underpinnings of the low-grade adipose inflammation
characteristic of diseases such as type 2 diabetes. Through employing a
comparative transcriptomics approach, we identified IRF1 as differentially
regulated between primary and in vitro-derived genetically matched adipocytes.
This suggests a role as a mediator of adipocyte inflammatory phenotypes, similar
to its function in other tissues. Utilizing adipose-derived mesenchymal
progenitors we subsequently demonstrated that expression of IRF1 in adipocytes
indeed contributes to upregulation of inflammatory processes, both in vitro and
in vivo. This highlights IRF1's relevance to obesity-related inflammation and the
resultant metabolic dysregulation.
PMID- 28416284
TI - Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic
Stem Cell Emergence, Migration, and Niche Colonization.
AB - Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from
hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically,
the cellular mechanism(s) allowing HSPC egress and migration to secondary niches
are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation
responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular
interactions, and signaling. Here, inhibition of vascular-associated Mmp2
function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb+
HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization;
these defects were absent in fibronectin mutants, indicating that Mmp2
facilitates endothelial-to-hematopoietic transition via ECM remodeling. In
contrast, Mmp9 was dispensable for HSPC budding, being instead required for
proper colonization of secondary niches. Significantly, these migration defects
were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine
12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine
regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary
roles in developmental HSPC production and migration.
PMID- 28416285
TI - Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron
Subclass Fate from Embryonic Stem Cells.
AB - Recent studies indicate that the location of neurogenesis within the medial
ganglionic eminence (MGE) critically influences the fate determination of
cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating
from subventricular zone divisions and somatostatin (Sst) interneurons primarily
arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate
the transition from apical to basal progenitor and their differentiation into
post-mitotic neurons. We find that aPKC inhibition enhances intermediate
neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly
increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of
Notch signaling enriches for Sst subtypes at the expense of Pv fates. These
findings confirm that the mode of neurogenesis influences the fate of MGE-derived
interneurons and provide a means of further enrichment for the generation of
specific interneuron subgroups from pluripotent stem cells.
PMID- 28416286
TI - In Vivo RNAi Screen Unveils PPARgamma as a Regulator of Hematopoietic Stem Cell
Homeostasis.
AB - Hematopoietic stem cell (HSC) defects can cause repopulating impairment leading
to hematologic diseases. To target HSC deficiency in a disease setting, we
exploited the repopulating defect of Fanconi anemia (FA) HSCs to conduct an in
vivo short hairpin RNA (shRNA) screen. We exposed Fancd2-/- HSCs to a lentiviral
shRNA library targeting 947 genes. We found enrichment of shRNAs targeting genes
involved in the PPARgamma pathway that has not been linked to HSC homeostasis.
PPARgamma inhibition by shRNA or chemical compounds significantly improves the
repopulating ability of Fancd2-/- HSCs. Conversely, activation of PPARgamma in
wild-type HSCs impaired hematopoietic repopulation. In mouse HSCs and patient
derived lymphoblasts, PPARgamma activation is manifested in upregulating the p53
target p21. PPARgamma and co-activators are upregulated in total bone marrow and
stem/progenitor cells from FA patients. Collectively, this work illustrates the
utility of RNAi technology coupled with HSC transplantation for the discovery of
novel genes and pathways involved in stress hematopoiesis.
PMID- 28416287
TI - Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial
Registration and Publications.
AB - We assessed the extent to which the publication of clinical trial results of
innovative cell-based interventions reflects International Society for Stem Cell
Research best practice guidelines. We assessed: (1) characteristics and time to
publication of completed trials; (2) quality of reported trials; and (3) results
of published trials. We identified and analyzed publications from 1,052 novel
stem cell clinical trials: 179 (45.4%) of 393 completed trials had published
results; 48 trials were registered by known stem cell tourism clinics, none of
which reported results. Completed non-industry-sponsored trials initially
published more rapidly, but differences with industry-sponsored trials decreased
over time. Most publications reported safety, and 67.3% (mainly early-stage
trials) reported positive outcomes. A higher proportion of industry trials
reported positive efficacy. Heightened patient expectations for stem cell
therapies give rise to ethical obligations for the transparent conduct of
clinical trials. Reporting guidelines need to be developed that are specific to
early-phase clinical trials.
PMID- 28416288
TI - Repeat Fibrinolysis to Treat Thrombotic Dysfunction of a Mitral Valve-in-valve
Prosthesis.
PMID- 28416289
TI - Impact of Autoimmune Disease on the Management and Prognosis of Acute Coronary
Syndrome.
PMID- 28416290
TI - Diagnostic and Prognostic Findings in Patients With Positive Clinical or ECG
Exercise Tests in the Absence of Echocardiographic Abnormalities.
PMID- 28416291
TI - Cumulative live birth rate after GnRH agonist trigger and elective
cryopreservation of all embryos in high responders.
AB - Elective embryo cryopreservation after using gonadotrophin-releasing hormone
(GnRH) antagonist protocols and GnRH agonist triggering is becoming an
increasingly important part of medically assisted reproduction. We designed a
single-centre retrospective study to assess the cumulative probability of
achieving a live birth through consecutive transfers of vitrified-warmed
blastocysts after elective embryo cryopreservation in high-responding patients.
Hence, 123 women identified to be at high risk for developing ovarian
hyperstimulation syndrome were included. They were stimulated using GnRH
antagonist protocol, and GnRH agonist was used to trigger final oocyte
maturation. All embryos were vitrified at the blastocyst stage and transferred in
the subsequent menstrual cycles. Using the Kaplan-Meier survival analysis, a
total of 65.9% (95% CI 57.5 to 74.3) women achieved a live birth after a maximum
of six embryo transfer cycles using the 'conservative' approach. Applying the
'optimistic' approach, presuming that women who still had cryopreserved embryos
and did not return for embryo transfer had the same chance of achieving a live
birth as those returning for transfer, the cumulative live birth rate estimated
in six embryo transfer cycles was 76.6% (95% CI 69.1 to 84.1). No cases of severe
ovarian hyperstimulation syndrome were recorded.
PMID- 28416292
TI - Participation of Emergency Radiologists in Tort Reform.
PMID- 28416293
TI - Sustaining Change in Radiology Education: The Need for Universal Curricula.
PMID- 28416294
TI - Radiologists May Now Be Accountable for Containing Medicare Costs and Spending
Under MACRA.
PMID- 28416295
TI - Depressive symptoms in schizophrenia and dopamine and serotonin gene
polymorphisms.
AB - Although depressive symptoms seem to be frequent in schizophrenia they have
received significantly less attention than other symptom domains. As impaired
serotonergic and dopaminergic neurotransmission is implicated in the pathogenesis
of depression and schizophrenia this study sought to investigate the putative
association between several functional gene polymorphisms (SERT 5-HTTLPR, MAO-A
VNTR, COMT Val158Met and DAT VNTR) and schizophrenia. Other objectives of this
study were to closely examine schizophrenia symptom domains by performing factor
analysis of the two most used instruments in this setting (Positive and negative
syndrome scale - PANSS and Calgary depression rating scale - CDSS) and to examine
the influence of investigated gene polymorphisms on the schizophrenia symptom
domains, focusing on depressive scores. A total of 591 participants were included
in the study (300 schizophrenic patients and 291 healthy volunteers). 192 (64%)
of schizophrenic patients had significant depressive symptoms. Genotype
distribution revealed no significant differences regarding all investigated
polymorphisms except the separate gender analysis for MAO-A gene polymorphism
which revealed significantly more allele 3 carriers in schizophrenic males.
Factor analysis of the PANSS scale revealed the existence of five separate
factors (symptom domains), while the CDSS scale revealed two distinct factors.
Several investigated gene polymorphisms (mostly SERT and MAO-A, but also COMT)
significantly influenced two factors from the PANSS (aggressive/impulsive and
negative symptoms) and one from the CDSS scale (suicidality), respectively.
Depressive symptoms in schizophrenic patients may be influenced by functional
gene polymorphisms, especially those implicated in serotonergic
neurotransmission.
PMID- 28416296
TI - HIV infection and aortic stiffness.
AB - People living with human immunodeficiency virus (HIV) infection and receiving
antiretroviral therapy now have the same life expectancy as the general
population. However, they have a higher risk of atherosclerotic cardiovascular
events because of a complex and polyfactorial vasculopathy, combining the effects
of antiretroviral therapy, the HIV virus itself, immune activation, chronic
inflammation and metabolic disturbances. Whether people living with HIV infection
experience increased vascular aging compared with the general population remains
controversial. To summarize current knowledge of the association between HIV
infection and aortic stiffness as a marker of vascular aging. This review
included 18 clinical studies in adult populations, published between 2009 and
2016, and identified on PubMed/MEDLINE or other databases. Search terms were
aortic stiffness, arterial stiffness, vascular aging, pulse wave velocity and
HIV. All 18 studies were observational, and compared groups infected (HIV+) and
not infected (HIV-) with HIV. Ten studies (55%) reported no significant
differences in aortic stiffness between HIV+ groups and age-matched HIV- control
groups. The main reported determinants of aortic stiffness were age, blood
pressure, smoking, metabolic syndrome and HIV-related variables, including
CD4/CD8 ratio, current T-CD4 count < 200/mm3 and nadir T-CD4+ count < 200/mm3. We
found discordant results regarding whether HIV+ patients had increased aortic
stiffness compared with HIV- controls. However, HIV-related conditions were
associated with vascular health. This association has been confirmed in recent
prospective studies. There is emerging evidence that HIV itself and immune
activity affect vascular health and the large arteries.
PMID- 28416297
TI - Cry toxin specificities of insect ABCC transporters closely related to
lepidopteran ABCC2 transporters.
AB - In this study, we examined insect and human ABCC transporters closely related to
the lepidopteran ABC transporter C2 (ABCC2), a powerful receptor for the Bacillus
thuringiensis Cry toxin, for their responses to various Cry toxins. ABCC2 and the
lepidopteran ABC transporter C3 (ABCC3) conferred cultured cells with
susceptibility to a lepidopteran-specific Cry1Aa toxin but not to lepidopteran
specific Cry1Ca and Cry1Da. One coleopteran ABCC transporter specifically
responded to a coleopteran-specific Cry8Ca toxin. ABCC transporters from a
dipteran insect and humans did not respond to any of the tested Cry toxins that
are active to lepidopteran and coleopteran insects. These results yield important
information for our understanding of insect specificity of Cry toxins and provide
the first demonstration of a coleopteran ABCC transporter that serves as a Cry
toxin receptor.
PMID- 28416298
TI - [Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by
antiepileptic drugs].
AB - INTRODUCTION: Antiepileptic drugs are widely used and are associated with
numerous side effects including skin eruptions. Epicutaneous tests have been used
with variable success in skin drug reactions. The purpose of this study was to
evaluate the profitability of epicutaneous tests in delayed hypersensitivity
reactions induced by antiepileptic drugs. METHODS: We analyzed all cases of
allergic skin reactions to antiepileptic drugs notified in regional
pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30,
2016. The imputation score, determined using the French imputation method, should
be at least doubtful. Patch-tests were performed in accordance with the general
Europen network on Drug Allergy/European Academy of Allergy and Clinical
Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the
generally accepted criteria of the International contact dermatitis research
group (ICDRG). RESULTS: In our study, 20 patients were included, among which 23
events were observed. The drug involved in delayed hypersensitivity reactions was
carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4
cases. The clinical reactions caused by the drug were classified as maculopapular
exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2
cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests
were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs
was observed in 4 cases: between valproic acid and carbamazepine in 2 cases
between valproic acid and phenobarbital in 1 case and between phenobarbital and
carbamazepine in 1 case. CONCLUSION: In this study, patch testing was a safe and
useful method in confirming the culprit drug in delayed hypersensitivity
reactions induced by antiepileptic drugs.
PMID- 28416299
TI - Malignant Mesothelioma of the Tunica Vaginalis Testis: Outcomes Following
Surgical Management Beyond Radical Orchiectomy.
AB - OBJECTIVE: To describe clinical management and outcomes of a cohort of patients
with malignant mesothelioma of the tunica vaginalis testis (MMTVT) who received
treatments beyond radical orchiectomy. METHODS: Patients with confirmed MMTVT at
a single tertiary care institution were identified. Treatments, pathologic
outcomes, and survival were recorded. Prognostic variables associated with
survival were analyzed with a Cox proportional hazards model and Kaplan-Meier
curves. RESULTS: Overall, 15 patients were included. Initial presentation was a
scrotal mass in 7 of 15 (47%) and hydrocele in 5 of 15 (33%) patients. Clinical
staging revealed enlarged nodes in 5 of 15 (33%) patients. Radical orchiectomy
was the initial treatment in 5 of 15 (33%) patients. Positive surgical margins
were found in 6 of 14 (43%) radical orchiectomies and were associated with worse
survival (P = .007). The most frequent histologic subtype was epithelioid,
associated with better survival (P = .048). Additional surgeries were performed
on 12 of 15 (80%) patients. Pathologic examination revealed MMTVT in 6 of 12
(50%) hemiscrotectomies, 7 of 8 (88%) retroperitoneal lymph node dissections, 1
of 7 (14%) pelvic lymph node dissections, and 10 of 10 (100%) groin dissections.
Five patients received adjuvant chemotherapy. Two also received adjuvant
radiation therapy. Three patients with lymph node involvement remain no evidence
of disease over 6 years after diagnosis. After a median follow-up of 3.5 years
(interquartile range: 1.2-7.2), 5 patients have died, all of MMTVT; the median
overall survival has not been reached. Common sites of relapse were lungs (5 of
7) and groin (3 of 7). CONCLUSION: The pattern of metastatic spread of MMTVT is
predominantly lymphatic. Nodes in the retroperitoneum and the groin are commonly
involved. Prognosis is poor, but there may be a role for aggressive surgical
resection including hemiscrotectomy, and inguinal and retroperitoneal lymph
nodes.
PMID- 28416301
TI - Telemedicine is the way forward for the management of cystic fibrosis - the case
in favour.
AB - Despite rapid changes in Information and Communication Technology, outpatient
chronic disease management has changed very little in decades. However, the
introduction of Telemedicine defined here as the use of remote patient-centred
clinical services including the use of video and audio connections,
telemonitoring and mobile applications provides us with an ideal opportunity to
revolutionise care. Its appeal in cystic fibrosis (CF) care is clear offering
better access to services, the opportunity of earlier intervention and improved
monitoring and self management through virtual clinics and the use of real-time
applications for adherence monitoring. It has the potential to reduce costs and
has been shown to be effective in other chronic disease conditions. There is a
lack of good quality data in CF and studies are needed to provide supportive
evidence. Nonetheless, it would seem that telemedicine is the future of CF care.
PMID- 28416300
TI - Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6
Deficient Mice.
AB - Soft tissue calcification occurs in several common acquired pathologies, such as
diabetes and hypercholesterolemia, or can result from genetic disorders. ABCC6, a
transmembrane transporter primarily expressed in liver and kidneys, initiates a
molecular pathway inhibiting ectopic calcification. ABCC6 facilitates the
cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a
major calcification inhibitor. Heritable mutations in ABCC6 underlie the
incurable calcification disorder pseudoxanthoma elasticum and some cases of
generalized arterial calcification of infancy. Herein, we determined that the
administration of PPi and the bisphosphonate etidronate to Abcc6-/- mice fully
inhibited the acute dystrophic cardiac calcification phenotype, whereas
alendronate had no significant effect. We also found that daily injection of PPi
to Abcc6-/- mice over several months prevented the development of pseudoxanthoma
elasticum-like spontaneous calcification, but failed to reverse already
established lesions. Furthermore, we found that the expression of low amounts of
the human ABCC6 in liver of transgenic Abcc6-/- mice, resulting in only a 27%
increase in plasma PPi levels, led to a major reduction in acute and chronic
calcification phenotypes. This proof-of-concept study shows that the development
of both acute and chronic calcification associated with ABCC6 deficiency can be
prevented by compensating PPi deficits, even partially. Our work indicates that
PPi substitution represents a promising strategy to treat ABCC6-dependent
calcification disorders.
PMID- 28416302
TI - Effect of Bacterial Biofilm on the Osteogenic Differentiation of Stem Cells of
Apical Papilla.
AB - INTRODUCTION: Although clinical success in regenerative endodontics is
substantially high, histological success is limited to finding bone/cementum-like
tissue instead of dentin within the canal space. The aims of this study were to
investigate (1) the effect of bacterial biofilm on osteogenic gene expression in
stem cells of the apical papilla (SCAP) and (2) the effect of bacterial antigens
on the functional differentiation of SCAP into a mineralizing phenotype. METHODS:
Using an ex vivo organotypic root canal model and an American Association of
Endontists-recommended regenerative endodontic procedures, we evaluated SCAP
differentiation in the presence and absence of an Enterococcus faecalis biofilm.
Gene expression analysis for dentinogenic and osteoblastic markers was performed
with real-time polymerase chain reaction. The effect of E. faecalis antigens on
SCAP differentiation into mineralizing cells in vitro was evaluated with 2
functional assays: Alizarin Red and alkaline phosphatase activity assays.
RESULTS: After regenerative endodontic procedures, residual bacteria continued to
sustain within the root canal system. SCAP in the presence of E. faecalis biofilm
significantly downregulated dentinogenic genes such as dentin sialophosphoprotein
and upregulated osteoblastic genes such as bone sialoprotein, osteocalcin, distal
less homeobox 5, and runt-related transcription factor 2. E. faecalis antigens
significantly inhibited SCAP differentiation into a mineralizing phenotype when
alizarin red staining and alkaline phosphatase assays were used in vitro.
CONCLUSIONS: Current disinfection protocols were ineffective in eliminating
bacteria from root tips and the levels of the residual bacterial biofilm, and its
byproducts, were able to significantly alter osteogenic-differentiation of SCAP.
PMID- 28416303
TI - Effect of Instrumentation Techniques and Preparation Taper on Apical Extrusion of
Bacteria.
AB - INTRODUCTION: The aim of this in vitro study was to evaluate the effects of
different root canal instrumentation techniques and preparation tapers on the
amount of apically extruded bacteria. METHODS: The root canals of 98 extracted
human mandibular incisors were contaminated with Enterococcus faecalis
suspension. After incubation at 37 degrees C for 24 hours, the root canals were
instrumented with K3 rotary files in a crown-down (CD) or full-length linear
instrumentation technique (FL) by using 3 different root canal tapers (0.02,
0.04, and 0.06). During instrumentation, apically extruded bacteria were
collected into vials containing saline solution. The microbiological samples were
taken from the vials and incubated in brain-heart agar medium for 24 hours, and
the numbers of colony-forming units (CFUs) were determined. The obtained results
were analyzed with t test and one-way analysis of variance for the comparisons
between the instrumentation techniques (CD and FL) and the preparation tapers
(0.02, 0.04, and 0.06), respectively. Tukey honestly significant difference test
was used for pairwise comparisons. RESULTS: The preparation taper had no effect
on the number of CFUs when a FL instrumentation technique was used (P > .05).
There was a statistically significant difference in the CFUs between FL and CD
techniques when the preparation taper was 0.02 (P < .05). There was no
statistically significant difference between the 0.04 and 0.06 preparation tapers
in any of the instrumentation techniques (P > .05). CONCLUSIONS: Using a 0.02
taper in a CD manner results in the least amount of bacterial extrusion. The
instrumentation technique did not seem to affect the amount of bacterial
extrusion when 0.04 and 0.06 taper instruments were used for cleaning and shaping
the root canal space.
PMID- 28416304
TI - Micro-computed Tomographic Analysis of Apical Microcracks before and after Root
Canal Preparation by Hand, Rotary, and Reciprocating Instruments at Different
Working Lengths.
AB - INTRODUCTION: This study aimed to compare apical microcrack formation after root
canal shaping by hand, rotary, and reciprocating files at different working
lengths using micro-computed tomographic analysis. METHODS: Sixty mandibular
incisors were randomly divided into 6 experimental groups (n = 10) according to
the systems and working lengths used for the root canal preparation: ProTaper
Universal for Hand Use (Dentsply Maillefer, Ballaigues, Switzerland), HyFlex CM
(Coltene-Whaledent, Allstetten, Switzerland), and Reciproc (VDW, Munich, Germany)
files working at the apical foramen (AF) and 1 mm short of the AF (AF - 1 mm).
The teeth were imaged with micro-computed tomographic scanning at an isotropic
resolution of 14 MUm before and after root canal preparation, and the cross
sectional images generated were assessed to detect microcracks in the apical
portion of the roots. RESULTS: Overall, 17 (28.3%) specimens presented
microcracks before instrumentation. Apical microcracks were present in 1
(ProTaper Universal for Hand Use), 3 (Hyflex CM), and 2 (Reciproc) specimens when
the instrumentation terminated at the AF. When instrumentation was terminated at
AF - 1 mm, apical microcracks were detected in 3 (ProTaper Universal for Hand
Use) and 4 (Hyflex CM and Reciproc) specimens. All these microcracks detected
after root canal preparation were already present before instrumentation, and no
new apical microcrack was visualized. For all groups, the number of slices
presenting microcracks after root canal preparation was the same as before canal
preparation. CONCLUSIONS: Root canal shaping with ProTaper Universal for Hand
Use, HyFlex CM, and Reciproc systems, regardless of the working length, did not
produce apical microcracks.
PMID- 28416305
TI - Fracture Strength of Endodontically Treated Teeth with Different Access Cavity
Designs.
AB - INTRODUCTION: The purpose of this study was to compare in vitro the fracture
strength of root-filled and restored teeth with traditional endodontic cavity
(TEC), conservative endodontic cavity (CEC), or ultraconservative "ninja"
endodontic cavity (NEC) access. METHODS: Extracted human intact maxillary and
mandibular premolars and molars were selected and assigned to control (intact
teeth), TEC, CEC, or NEC groups (n = 10/group/type). Teeth in the TEC group were
prepared following the principles of traditional endodontic cavities. Minimal
CECs and NECs were plotted on cone-beam computed tomographic images. Then, teeth
were endodontically treated and restored. The 160 specimens were then loaded to
fracture in a mechanical material testing machine (LR30 K; Lloyd Instruments Ltd,
Fareham, UK). The maximum load at fracture and fracture pattern (restorable or
unrestorable) were recorded. Fracture loads were compared statistically, and the
data were examined with analysis of variance and the Student-Newman-Keuls test
for multiple comparisons. RESULTS: The mean load at fracture for TEC was
significantly lower than the one for the CEC, NEC, and control groups for all
types of teeth (P < .05), whereas no difference was observed among CEC, NEC, and
intact teeth (P > .05). Unrestorable fractures were significantly more frequent
in the TEC, CEC, and NEC groups than in the control group in each tooth type (P <
.05). CONCLUSIONS: Teeth with TEC access showed lower fracture strength than the
ones prepared with CEC or NEC. Ultraconservative "ninja" endodontic cavity access
did not increase the fracture strength of teeth compared with the ones prepared
with CEC. Intact teeth showed more restorable fractures than all the prepared
ones.
PMID- 28416306
TI - Histologic Findings of a Human Immature Revascularized/Regenerated Tooth with
Symptomatic Irreversible Pulpitis.
AB - INTRODUCTION: Pulp revascularization/regeneration in immature permanent teeth
with necrotic pulp and/or apical periodontitis is an effective approach for
inducing root maturation. Previous histologic studies showed cementoid/osteoid
tissue and/or periodontal ligament-like tissue formed within the root canals.
This case report describes the histologic findings of a human symptomatic
irreversible pulpitis immature permanent tooth with most of the pulp removed
after a revascularization/regeneration procedure. METHODS: A human immature
permanent mandibular premolar (tooth #29) was diagnosed as symptomatic
irreversible pulpitis with symptomatic apical periodontitis at the emergency
department. Most of the pulp was removed. The tooth was treated with
revascularization/regeneration. RESULTS: At the 12-month recall, the radiographic
examination revealed thickening of the root canal wall, narrowing of the root
apex, and lengthening of the root. The tooth was extracted at 12 months for
orthodontic treatment. The specimens were processed for histologic examination.
Histologically, the apical third of the root canal was filled with newly formed
dentinlike and pulplike tissue. There was a layer of flattened odontoblastlike
cells lining the dentinal wall. In the midportion of the root canal, the newly
formed dentinlike tissue gradually changed to cementumlike tissue. In the upper
third of the root canal, there was a presence of cementocytelike cells housed in
the lacunae of cementumlike tissue around the loose connective tissue.
CONCLUSIONS: In the present case, regeneration of the pulplike tissue and the
periodontium existed after a revascularization/regeneration procedure in an
immature permanent tooth clinically diagnosed as symptomatic irreversible
pulpitis.
PMID- 28416307
TI - The Efficacy of the WaveOne Reciprocating File System versus the ProTaper
Retreatment System in Endodontic Retreatment of Two Different Obturating
Techniques.
AB - INTRODUCTION: This ex vivo study aimed to evaluate the efficacy of retreating
GuttaCore (Dentsply Tulsa Dental Specialties, Tulsa, OK) and warm vertically
condensed gutta-percha in moderately curved canals with 2 different systems:
ProTaper Universal Retreatment (Dentsply Tulsa Dental) and WaveOne (Dentsply
Tulsa Dental). METHODS: Eighty mesial roots of mandibular molars were used in
this study. The mesiobuccal canals in each sample were prepared to length with
the WaveOne Primary file (Dentsply Tulsa Dental). The canals were obturated with
either a warm vertical approach or with GuttaCore and divided into 4 retreatment
groups with the same mean root curvature: warm vertical retreated with ProTaper,
warm vertical retreated with WaveOne, GuttaCore retreated with ProTaper, and
GuttaCore retreated with WaveOne. The warm vertical groups were obturated using a
continuous-wave technique of gutta-percha compaction, and the GuttaCore groups
were obturated according to the manufacturer's instructions. After allowing
sealer to set, each specimen was retreated with either the ProTaper Universal
Retreatment files D1, D2, or D3 or with the WaveOne Primary file to the
predetermined working length. The time taken to reach the working length was
recorded. Instrument fatigue and failure were also evaluated. RESULTS: The post
hoc 2-sample t tests showed that the overall mean total time taken to reach the
working length for the warm vertical groups was significantly greater than that
observed for the GuttaCore groups (mean = 87.11 vs 60.16 seconds, respectively),
and the overall mean total time taken to reach the working length for WaveOne was
significantly greater than that observed for ProTaper (99.09 vs 48.18 seconds,
respectively). Two-way analysis of variance showed a significant main effect for
both the type of experiment groups (F1,76 = 15.32, P = .0002) and the type of
retreatments (F1,76 = 54.67, P < .0001). Also, the WaveOne Primary file underwent
more separations than the ProTaper files. CONCLUSIONS: The WaveOne Primary file
underwent more separations and was unable to remove gutta-percha as efficiently
as the ProTaper Universal Retreatment files. Also, canals obturated with
GuttaCore were retreated more efficiently and with fewer file separations than
the canals obturated using continuous wave of warm gutta-percha.
PMID- 28416308
TI - Implantation of Endothelial Cells with Mesenchymal Stem Cells Accelerates Dental
Pulp Tissue Regeneration/Healing in Pulpotomized Rat Molars.
AB - INTRODUCTION: This study aimed to examine whether the implantation of mesenchymal
stem cells (MSCs) with endothelial cells (ECs) accelerates pulp tissue
regeneration/healing and induces dentin bridge formation in a rat model of molar
coronal pulp regeneration. METHODS: The maxillary first molars of Wistar rats
were subjected to pulpotomy. Then, pulp chambers were implanted with
biodegradable hydrogel-made scaffolds carrying MSCs together or without dermal
microvascular ECs, and the cavities were sealed with mineral trioxide aggregate.
After 14 days, pulp samples were analyzed by immunohistochemistry; messenger RNA
expression of B-cell lymphoma 2 (Bcl-2), chemokine (C-X-C motif) ligand 1
(Cxcl1), CXC receptor 2 (Cxcr2), and dentin sialophosphoprotein (Dspp) by
quantitative polymerase chain reaction, and protein expression of nestin and
vascular endothelial growth factor by Western blotting. RESULTS: Teeth
coimplanted with MSCs and ECs showed pulp healing with complete dentin bridge
formation, whereas those implanted with MSCs alone had incomplete dentin bridges.
Bcl-2, Cxcl1, Cxcr2, and Dspp messenger RNA levels were significantly up
regulated in the pulp of MSC/EC-implanted teeth compared with those in MSC
implanted teeth. Immunohistochemical analysis revealed the expression of nestin
in odontoblastlike cells under dentin bridges in the MSC/EC coimplanted group.
The density of CD31-expressing ECs and the expression of nestin and vascular
endothelial growth factor proteins were significantly up-regulated in the MSC/EC
implanted pulp compared with the MSC-implanted pulp. CONCLUSIONS: The
implantation of ECs with MSCs accelerated pulp tissue regeneration/healing and
dentin bridge formation, up-regulated the expression of proangiogenic factors,
and increased the density of ECs in pulpotomized rat molars.
PMID- 28416309
TI - Detection of Apical Root Cracks Using Spectral Domain and Swept-source Optical
Coherence Tomography.
AB - INTRODUCTION: This study aimed to evaluate the ability of 2 optical coherence
tomographic (OCT) systems to detect apical dentinal microcracks. METHODS: Twenty
extracted human single-rooted mandibular incisors were selected. After root canal
preparation with an R40 Reciproc file (VDW, Munich, Germany), the specimens
presenting apical microcracks were identified using micro-computed tomographic
(micro-CT) scanning as the gold standard. Then, the apical portions of the roots
were imaged with spectral domain OCT (SD-OCT) and swept-source OCT systems, and
the resulting images were blindly evaluated by 3 independent examiners to detect
microcracks. The diagnostic performance of each OCT device was calculated, and
statistical analysis was performed. RESULTS: Based on the micro-CT images, 12
(60%) roots presented dentinal microcracks in the apical region. The images
generated by the OCT systems were able to show microcrack lines at the same
location as the corresponding micro-CT cross sections. Although the diagnostic
performance of the SD-OCT device was superior, there were no statistically
significant differences between the 2 OCT devices (P > .05). Interexaminer
agreement was substantial to almost perfect for the SD-OCT system and moderate to
almost perfect for the swept-source OCT system, whereas intraexaminer agreement
was substantial to almost perfect for both OCT devices. CONCLUSIONS: The
detection ability verified for both OCT systems renders them promising tools for
the diagnosis of apical microcracks.
PMID- 28416310
TI - Cracked Teeth and Poor Oral Masticatory Habits: A Matched Case-control Study in
China.
AB - INTRODUCTION: Previous studies have suggested that masticatory forces are
associated with cracked teeth, but it is not clear which specific poor oral
masticatory habits may be more likely to cause cracks. The aim of this study was
to quantitatively assess risk factors for cracked teeth among poor oral
masticatory habits and create a model for individualized risk predictions.
METHODS: We enrolled 35 patients with cracked teeth matched to 70 controls
without cracked teeth by age, sex, position of the affected tooth,
presence/absence of systemic disease, and diagnosis of symptomatic irreversible
pulpitis from the Stomatology Hospital of Tianjin Medical University, Tianjin,
China. Odds ratios (ORs) were calculated using conditional logistic regression
analysis. RESULTS: Thermal cycling eating habits (OR = 3.296; 95% confidence
interval [CI], 1.684-6.450), eating coarse foods (OR = 2.727; 95% CI, 1.340
5.548), chewing on hard objects (OR = 2.087; 95% CI, 1.041-4.182), and unilateral
mastication (OR = 2.472; 95% CI, 1.255-4.869) were independent risk factors for
cracked teeth. The corresponding risk scores were 2.182, 1.691, 1.467, and 1.589,
respectively. The area under the receiver operating characteristic curve and its
95% CI were 0.920 (0.868-0.973); the sensitivity and specificity were 0.943 and
0.800, respectively. CONCLUSIONS: Thermal cycling eating habits were strongly
associated with cracked teeth, whereas eating coarse foods, chewing on hard
objects, and unilateral mastication were also independent risk factors for
cracked teeth. These findings yield insights into ways to promote the prevention
of risky behaviors for cracked teeth.
PMID- 28416311
TI - Complicated Root Canal Configuration of Mandibular First Premolars Is Correlated
with the Presence of the Distolingual Root in Mandibular First Molars: A Cone
beam Computed Tomographic Study in Taiwanese Individuals.
AB - INTRODUCTION: The purpose of this study was to examine the frequency and
bilateral consistency of distolingual roots (DLRs) in permanent mandibular first
molars (PMFMs) and root canal configurations in PMFPs (permanent mandibular first
premolars) and to determine the correlation between the root canal configurations
of PMFPs with the appearance of DLRs in PMFMs. METHODS: A total of 932 cone-beam
computed tomographic images of PMFMs and PMFPs were collected from 233 patients.
The frequency and bilateral consistency of DLRs in PMFMs along with root canal
configurations (root number and canal number) of PMFPs were recorded and
evaluated ipsilaterally and contralaterally. Multivariable logistic regression
analysis was used to evaluate the correlation between the root canal
configurations of PMFPs with the appearance of DLRs in PMFMs. RESULTS: The
prevalence of PMFMs with DLRs was 24.7%, and the incidence of complicated root
canal configurations of PMFPs was 26.6%. The incidence of complicated root canal
configurations of PMFPs was 19.6% in the non-DLR group, 37.2% in the unilateral
DLR group, and 44.7% in the bilateral DLR group. After adjusting for categoric
variables including sex, age, and side, the odds ratios for the frequency of
complicated root canal configurations of PMFPs in the unilateral DLR and
bilateral DLR groups compared with the non-DLR group were 2.472 (95% confidence
interval, 1.434-4.263; P = .001) and 3.392 (95% confidence interval, 1.976-5.823;
P < .001), respectively. CONCLUSIONS: An increasing and corresponding trend
between the presence of DLRs in PMFMs and complicated root canal configurations
in PMFPs was noted in Taiwanese individuals. These results suggest that the
clinicians should familiarize themselves with the anatomic variants of PMFMs and
PMFPs before endodontic treatment.
PMID- 28416312
TI - Periapical Lesions Increase Macrophage Infiltration and Inflammatory Signaling in
Muscle Tissue of Rats.
AB - INTRODUCTION: Our previous studies have shown that periapical lesions (PLs) in
rats cause systemic disorders such as increased tumor necrosis factor-alpha
plasma levels, insulin resistance, and impairment in insulin signal transduction
in muscle tissue. However, the mechanisms involved in these alterations are not
fully understood. Under chronic inflammatory conditions such as obesity, it has
been shown that the skeletal muscle is affected by inflammation, and the number
of resident macrophages that are associated with impairments of insulin action
and sensitivity is increased. This study aimed to investigate the presence of
macrophages, activation of inflammatory pathways in muscle tissue, glycemia, and
insulinemia of rats with PLs. METHODS: Sixty Wistar rats were distributed into a
control group; a group with 1 PL (1PL), which was induced in the right maxillary
first molar; and a group with 4 PLs (4PL), which were induced in the right upper
and lower first and second molars. We quantified macrophage content by
immunohistochemistry for the F4/80 protein. We evaluated Jun N-terminal kinase
and IKKalpha/beta phosphorylation status in the muscle tissue by Western
blotting. Serum levels of lipopolysaccharide (LPS) and HSP70 and plasma levels of
glucose and insulin were assessed by using commercial kits. RESULTS: The 1PL and
4PL groups showed increase in macrophage content, IKKalpha/beta, and Jun N
terminal kinase phosphorylation status, serum LPS and HSP70 levels, and insulin
resistance and no changes in glycemia and insulinemia compared with the control
group. There was no difference in these parameters between the 1PL and 4PL
groups. CONCLUSIONS: PLs promoted an increase in macrophage infiltration,
activation of inflammatory pathways in muscle tissue, and serum concentrations of
HSP70 and LPS in rats. The present study improves the knowledge on the impact of
oral inflammations on the development of systemic alteration, which can induce
insulin resistance.
PMID- 28416313
TI - Changes of Periodontal Parameters after Apical Surgery: Correlation of Clinical
and Cone-beam Computed Tomographic Data.
AB - INTRODUCTION: The purpose of this study was to evaluate the changes of the
marginal periodontium 1 year after apical surgery. METHODS: Clinical and
radiographic (cone-beam computed tomographic) examinations of 54 teeth treated
with buccal access flaps for apical surgery were performed at baseline and after
1 year. Clinical assessment included measurements of probing pocket depth, the
level of gingival margin (GM), and the width of keratinized tissue. Subsequently,
the clinical attachment level (CAL) and the width of the attached gingiva were
calculated. On bucco-oral cone-beam computed tomographic sections, the height and
thickness of the crestal bone and the thickness of the alveolar bone were
measured at different levels. RESULTS: In general, the calculated mean changes of
periodontal tissue and crestal/alveolar bone were only minimal. Significant mean
changes included only GM and CAL on midoral aspects and the distance from the
cementoenamel junction or restoration margin on midbuccal sites. CAL was further
correlated with the thickness of the alveolar bone at 3 mm below the
cementoenamel junction or restoration margin. None of the clinically and
radiographically calculated mean changes were correlated with sex, biotype, or
incision techniques. With regard to age, older patients showed significantly more
gingival recession on the buccal aspect compared with younger individuals.
Furthermore, mean changes of the midbuccal width of the attached gingiva were
positively correlated with the healing outcome, whereas mean changes of the
midoral GM and CAL were negatively correlated with the healing outcome.
CONCLUSIONS: Within an observation period of 1 year, the marginal periodontium
and its underlying bone structures did not suffer from significant changes after
apical surgery.
PMID- 28416314
TI - The Use of a Novel Approach for the Instrumentation of a Cone-beam Computed
Tomography-discernible Lateral Canal in an Unusual Maxillary Incisor: Case
Report.
AB - Lateral and apical ramifications of the main root canal create potential pathways
through which bacteria can spread and remain unaffected by treatment procedures.
It is a challenge for the specialty to find techniques that can predictably
reach, disinfect, and obturate these ramifications. Here, we report the use of a
novel instrumentation approach to aid in the negotiation and management of a
lateral canal discernible on cone-beam computed tomography (CBCT) in an unusual
maxillary central incisor. A 23-year-old female patient was referred for
evaluation and possible treatment of tooth 9. The periapical radiographic
examination revealed pulp chamber obliteration, existence of a lateral lesion,
and a possible complex internal root canal anatomy. The CBCT evaluation revealed
the existence of a lateral lesion, a periapical lesion, an additional
distopalatal canal, and a lateral canal exiting at the lateral lesion. The
diagnosis of asymptomatic apical and lateral periodontitis of tooth 9 was
reached. CBCT-aided access cavity preparation and scouting resulted in the
successful negotiation of all canals, main and lateral. A novel instrumentation
technique with precurved controlled memory files was used for the mechanical
preparation of the lateral canal to a 25/04 enlargement. Obturaton of the lateral
canal was achieved with a single gutta-percha cone and AH Plus Root Canal Sealer.
At the 2-year follow-up, the patient was asymptomatic, and the 2-dimensional
radiographic examinations revealed resolution of both the periapical and the
lateral lesions. This case report describes the application of a novel
instrumentation technique for the mechanical debridement of an infected lateral
canal discernible on CBCT and reinforces the importance of treating the root
canals as systems that possesses anatomic intricacies that need to be addressed.
PMID- 28416315
TI - Preparation of Oval-shaped Canals with TRUShape and Reciproc Systems: A Micro
Computed Tomography Study Using Contralateral Premolars.
AB - INTRODUCTION: The purpose of this study was to compare the shaping properties of
TRUShape and Reciproc systems during preparation of oval-shaped canals from
contralateral teeth by using micro-computed tomography scanning. METHODS:
Thirteen pairs of freshly extracted contralateral mandibular premolars with a
single oval-shaped canal were selected and divided into 2 groups according to the
root canal instrumentation technique, TRUShape and Reciproc. The final apical
size of instrumentation was 40/.06 for both systems. Data were statistically
analyzed for the increase in canal volume and surface area and the amount of
unprepared areas promoted by the 2 systems. RESULTS: Preparation with both
systems significantly increased the volume and area of the canals (P < .001),
with no significant differences between them (P > .05). When the full canal
length was evaluated, the amount of uninstrumented areas was significantly larger
for Reciproc (30%) than TRUShape (24%) (P < .05). However, analysis restricted to
the apical 4-mm segment revealed no statistically significant difference in
untouched areas (25% for Reciproc and 20% for TRUShape) (P > .05). CONCLUSIONS:
Both instrument systems behaved similarly in promoting the increase of root canal
volume and surface area. When the full canal length was evaluated, TRUShape
instruments showed less unprepared areas than Reciproc. However, this difference
did not occur for the apical part of the root canal. None of the techniques could
completely prepare oval-shaped root canals.
PMID- 28416316
TI - Effect of Passive Ultrasonic Activation on Organic Tissue Dissolution from
Simulated Grooves in Root Canals Using Sodium Hypochlorite with or without
Surfactants and EDTA.
AB - INTRODUCTION: The aim of this study was to evaluate the porcine palatal mucosa
dissolution from artificial grooves using a final rinse with sodium hypochlorite
(NaOCl) with or without a surfactant or ultrasonic activation (PUI). METHODS: The
root canals of 130 human maxillary central incisors were chemomechanically
prepared and the teeth split. A standardized longitudinal intracanal groove was
created in 1 of the root halves. One hundred thirty porcine palatal mucosa
samples were collected, adapted in order to fit into the grooves, and weighed.
The reassembled specimens were randomly divided in 3 experimental groups (n = 40)
based on their irrigation protocol (ie, positive pressure [PP] and PUI during 15
[PUI-15] or 30 seconds [PUI-30]) and divided in subgroups according to the NaOCl
preparation used: Vista 6% plain (Vista Dental Products, Racine, WI) or Chlor
XTRA (Vista Dental Products) (containing surfactant). An EDTA intermediate rinse
was included. Palatal mucosa weights were measured after the assays. The
intergroup weight changes were statistically analyzed. RESULTS: Complete
dissolution did not occur in any sample. Chlor-XTRA subgroups were associated
with increased weight reduction compared with Vista 6% plain subgroups; however,
the differences were significant (P < .05) only for PP and PUI-15. PUI-30
increased weight reduction compared with PP for both hypochlorites and PUI-15
using Vista 6% plain (P < .05). PUI-30 with Vista 6% plain performed
significantly better than PP with Chlor-XTRA (P < .05). CONCLUSIONS: The addition
of a surfactant to NaOCl and/or PUI activation increased palatal mucosa
dissolution within artificial grooves in the root canal of incisor teeth. PUI
agitation was often able to compensate for the absence of surfactants.
PMID- 28416317
TI - Zinc Oxide Inhibits Dental Discoloration Caused by White Mineral Trioxide
Aggregate Angelus.
AB - INTRODUCTION: The aim of the study was to investigate the addition of variable
amounts of zinc oxide to inhibit dental discoloration caused by mineral trioxide
aggregate (MTA) Angelus. METHODS: MTA Angelus and MTA with additions of 5%, 15%,
and 45% zinc oxide (ZnO) in weight were tested. The set cements were
characterized by using a combination of scanning electron microscopy, energy
dispersive spectroscopy, and x-ray diffraction. Radiopacity and setting time were
analyzed according to American National Standards Institute/American Dental
Association (57/2012) and American Society for Testing and Materials (C266-08).
Volume change was evaluated by using micro-computed tomography analysis. The pH
and calcium ion release were measured after 3 hours, 24 hours, and 28 days.
Dental discoloration in contact with the cements was measured after 24 hours, 28
days, and 90 days. Biocompatibility to subcutaneous implantation in rats was
verified after 30 and 60 days. RESULTS: Addition of ZnO did not alter
significantly the radiopacity, setting time, volume change, pH, and
biocompatibility compared with MTA Angelus (P > .05). Calcium ion release
increased with addition of ZnO (P < .05). Proportions of 15% and 45% ZnO
interfered in hydration. The 5% ZnO addition was sufficient to prevent the dental
discoloration observed with MTA Angelus. CONCLUSIONS: The addition of 5%, 15%, or
45% zinc oxide to MTA Angelus inhibits dental discoloration without modifying the
radiopacity, setting time, volume change, pH, and biocompatibility.
PMID- 28416318
TI - Basic Fibroblast Growth Factor Regulates Gene and Protein Expression Related to
Proliferation, Differentiation, and Matrix Production of Human Dental Pulp Cells.
AB - INTRODUCTION: Basic fibroblast growth factor (bFGF) plays differential effects on
the proliferation, differentiation, and extracellular matrix turnover in various
tissues. However, limited information is known about the effect of bFGF on dental
pulp cells. The purposes of this study were to investigate whether bFGF
influences the cell differentiation and extracellular matrix turnover of human
dental pulp cells (HDPCs) and the related gene and protein expression as well as
the role of the mitogen-activated protein kinase (MEK)/extracellular-signal
regulated kinase (ERK) signaling pathway. The expression of fibroblast growth
factor receptors (FGFRs) in HDPCs was also studied. METHODS: The expression of
FGFR1 and FGFR2 in HDPCs was investigated by reverse-transcription polymerase
chain reaction. HDPCs were treated with different concentrations of bFGF. Cell
proliferation was evaluated using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl
tetrazolium bromide assay. Cell differentiation was evaluated using alkaline
phosphatase (ALP) staining. Changes in messenger expression of cyclin B1 and
tissue inhibitor of metalloproteinase (TIMP) 1 were determined by reverse
transcription polymerase chain reaction. Changes in protein expression of cdc2,
TIMP-1, TIMP-2, and collagen I were determined by Western blotting. U0126 was
used to clarify the role of MEK/ERK signaling. RESULTS: HDPCs expressed both
FGFR1 and FGFR2. Cell viability was stimulated by 50-250 ng/mL bFGF. The
expression and enzyme activities of ALP were inhibited by 10-500 ng/mL bFGF. At
similar concentrations, bFGF stimulates cdc2, cyclin B1, and TIMP-1 messenger RNA
and protein expression. bFGF showed little effect on TIMP-2 and partly inhibited
collagen I expression of pulp cells. U0126 (a MEK/ERK inhibitor) attenuated the
bFGF-induced increase of cyclin B1, cdc2, and TIMP-1. CONCLUSIONS: bFGF may be
involved in pulpal repair and regeneration by activation of FGFRs to regulate
cell growth; stimulate cdc2, cyclin B1, and TIMP-1 expression; and inhibit ALP.
These events are partly associated with MEK/ERK signaling.
PMID- 28416320
TI - Predictive Value of Using Initial Versus Terminal Deceased Donor Creatinine to
Calculate the Kidney Donor Risk Index.
PMID- 28416319
TI - Feasibility of Cone-beam Computed Tomography in Detecting Lateral Canals before
and after Root Canal Treatment: An Ex Vivo Study.
AB - INTRODUCTION: The study objective was to evaluate the effectiveness of cone-beam
computed tomographic (CBCT) imaging for the detection of lateral canals (LCs) in
endodontically treated premolars. METHODS: Two evaluators classified 80 extracted
premolars into 2 groups based on the absence (n = 40) or presence (n = 40) of LCs
according to micro-computed tomographic analysis. The extracted teeth were
fixated in a human mandible and scanned with CBCT imaging. Subsequently, each
tooth was endodontically treated, and CBCT scans were repeated. Three experienced
examiners evaluated all images randomly. Receiver operating characteristic curves
were compared using the McNemar test, and sensitivity, specificity, positive
predictive value, and negative predictive value (NPV) were obtained. RESULTS: The
area under the receiver operating characteristic curve values were 0.58 and 0.49
before and after root canal treatment, respectively. These values were
statistically significantly different (P < .001). Before root canal treatment
sensitivity, specificity, positive predictive value, and negative predictive
value were 55%, 52%, 55%, and 56%, whereas after root canal treatment the values
were 33%, 61%, 46%, and 48%, respectively. CONCLUSIONS: LC detection in
nontreated teeth presented low accuracy, whereas among treated teeth CBCT imaging
showed no efficacy. The results suggest that CBCT imaging is not an effective
diagnostic tool for LC detection.
PMID- 28416321
TI - Targeted Deprescribing in an Outpatient Hemodialysis Unit: A Quality Improvement
Study to Decrease Polypharmacy.
AB - BACKGROUND: Polypharmacy in hemodialysis patients can result in adverse patient
outcomes. Deprescribing tools can reduce polypharmacy, yet no method exists for
an outpatient hemodialysis population. DESIGN: Quality improvement study. SETTING
& PARTICIPANTS: 240 patients in a tertiary-care outpatient hemodialysis unit.
QUALITY IMPROVEMENT PLAN: We aimed to: (1) develop a deprescribing tool for
target medications with poor evidence for efficacy and safety, (2) determine its
effectiveness in decreasing polypharmacy, and (3) monitor patient safety and
satisfaction. OUTCOMES: The primary outcome was the proportion of target
medications completely deprescribed after 4 weeks. Secondary outcomes were the
proportion of target medications completely deprescribed after 6 months, average
number of medications per patient before and after deprescription, and proportion
of successful deprescriptions for each target medication. MEASUREMENTS: Number of
medications deprescribed at 4 weeks and 6 months. Patient safety and satisfaction
were monitored using drug-specific monitoring parameters. RESULTS: A
deprescribing tool for specific medications was developed and implemented in the
hemodialysis unit. 5 medication classes were selected: quinine, diuretics, alpha1
blockers, proton pump inhibitors, and 3-hydroxy-3-methylglutaryl-coenzyme A
reductase inhibitors (statins). All 240 patients in the unit were screened using
the deprescribing tool. There were 171 of 240 (71%) patients prescribed at least
1 of the 5 target medications, and after applying the tool, 35 of 40 (88%)
eligible patients had the medications deprescribed. There were 31 of 40 (78%)
target medications completely deprescribed. 6 months after the study, only 5 of
31 (16%) medications discontinued were represcribed. At the end of the study, 57%
of patients were taking fewer medications than at baseline. No adverse events
were observed. LIMITATIONS: Single-center study that relied on patient self
reporting of medication use and adherence to our recommendations. CONCLUSIONS:
Deprescribing tools can be applied successfully in an outpatient hemodialysis
unit to reduce polypharmacy while maintaining patient safety and satisfaction.
PMID- 28416322
TI - Nephrologists and Integrated Kidney Disease Care: Roles and Skills Essential for
Nephrologists for Future Success.
AB - As the costs of caring for patients with end-stage renal disease have grown, so
has the pressure to provide high-quality care at a lower cost. Prompted in large
part by regulatory and legislative changes, reimbursement is shifting from a fee
for-service environment to one of value-based payment models. Nephrologists in
this new environment are increasingly responsible not only for direct patient
care, but also for population management and the associated clinical outcomes for
this vulnerable population. This Perspective article aims to recognize the key
role and skills needed in order to successfully practice within these new value
based care models. The new paradigm of delivering and financing care also
presents opportunities for nephrologists to shape how care is delivered, define
meaningful quality metrics, and share in the financial outcomes of these
approaches. Though it will take time, the training and mind-set of nephrologists
must evolve to accommodate these expanded practice expectations required by a
system that demands measurement, reporting, accountability, and improvement, not
only for individuals but also for populations of patients.
PMID- 28416323
TI - Review of coronary subclavian steal syndrome.
AB - The clinical benefits of using the left internal mammary artery (LIMA) to bypass
the left anterior descending artery are well established making it the most
frequently used conduit for coronary artery bypass surgery (CABG). Coronary
subclavian steal syndrome (CSSS) occurs during left arm exertion when (1) the
LIMA is used during bypass surgery and (2) there is a high grade (>=75%) left
subclavian artery stenosis or occlusion proximal to the ostia of the LIMA
resulting in "stealing" of the myocardial blood supply via retrograde flow up the
LIMA graft to maintain left upper extremity perfusion. Although CSSS was once
thought to be a rare phenomenon, its prevalence has been underestimated and is
becoming increasingly recognized as a serious threat to the success of CABG.
Current guidelines are lacking on recommendations for screening of subclavian
artery stenosis (SAS) pre- and post-CABG. We hope to provide an algorithm for SAS
screening to prevent CSSS in internal mammary artery bypass recipients and review
treatment options in the percutaneous era.
PMID- 28416324
TI - E4BP4 mediates glucocorticoid-regulated adipogenesis through COX2.
AB - Adipogenesis is mediated by glucocorticoids via transcriptional regulation of
glucocorticoid receptor (GR) target genes. However, the mechanism by which GR
participates in adipogenesis has hitherto been poorly characterized. In this
study, E4 promoter-binding protein 4 (E4BP4) was found to have a critical role in
adipogenic differentiation of preadipocytes. Gain-of-function and loss-of
function studies revealed that E4BP4 acts as a positive regulator of adipogenesis
in 3T3-L1 cells. E4BP4 was markedly induced by glucocorticoid (dexamethasone) via
GR and cAMP response element-binding protein (CREB) during adipogenesis.
Knockdown of E4BP4 abolished dexamethasone-induced adipogenesis, and
overexpression of E4BP4 partially accounted for the actions of dexamethasone in
adipogenic differentiation. Promoter deletion analysis confirmed that E4BP4
transcriptionally represses COX2 promoter activity, whereas COX2 overexpression
reversed the acceleration of E4BP4 in adipogenesis. Thus, E4BP4 acts as a key pro
adipogenic transcription factor by trans-repressing COX2 in glucocorticoid
associated adipocyte differentiation.
PMID- 28416325
TI - Involvement of the nuclear progestin receptor in LH-induced expression of
membrane type 2-matrix metalloproteinase required for follicle rupture during
ovulation in the medaka, Oryzias latipes.
AB - Hormonal regulation of the expression of Mmp15, a proteolytic enzyme
indispensable for ovulation in the teleost medaka, was investigated. In an in
vitro culture system using preovulatory follicles, Mmp15 expression and ovulation
were induced in the presence of recombinant luteinizing hormone (rLh). Both rLh
induced Mmp15 expression and ovulation were 17alpha, 20beta-dihydroxy-4-pregnen-3
one-dependent, suggesting the involvement of a nuclear progestin receptor (Pgr).
In vitro follicle ovulation and Mmp15 expression were reduced by treatment with
the Pgr antagonist RU-486. Like Pgr, the transcription factor CCAAT/enhancer
binding protein beta (Cebpb) was induced by rLh. ChIP analyses indicated that Pgr
and Cebpb bound to the mmp15 promoter region. These results indicate that the rLh
induced expression of Mmp15 is mediated by Pgr and Cebpb. A differential timing
of expression of Pgr and Cebpb in the preovulatory follicles appears to explain
the considerably long time-lag from the pgr gene activation to mmp15 gene
expression.
PMID- 28416326
TI - Reply to comment on "Combination of cupric ion with hydroxylamine and hydrogen
peroxide for the control of bacterial biofilms on RO membranes by Hye-Jin Lee,
Hyung-Eun Kim, Changha Lee [Water Research 110, 2017, 83-90]".
PMID- 28416328
TI - Hepatoprotective Mongolian prescription II enhances the antitumor effects of
chemotherapeutics in hepatocellular carcinoma xenografts.
AB - Hepatoprotective Mongolian prescription II (MPII), a mixture of 18 different
medicinal herbs, significantly inhibited the growth of human liver cancer cell
lines Huh-7 and HepG2 in vitro with different concentrations; MPII (6mg/mL)
inhibited cell proliferation by 80.48%. MPII induced apoptosis in both cell
lines, which was observed by light microscopy and flow cytometry. MPII-induced
apoptosis and G0/G1 cell cycle arrest were quantified by Annexin V-FITC/PI
staining and flow cytometry. At the molecular level, MPII induced caspase-3,
caspase-8, caspase-9, and cytochrome c gene expression. In vivo, MPII
dramatically inhibited human liver tumor growth in a xenograft model in Kunming
mice with no apparent cytotoxicity to the hosts. Apoptotic genes (Bcl-2 and Bax)
are up-regulated, suggesting that the ratio of Bcl-2/Bax was statistically
significant, indicating that the drugs had affected the expression of apoptosis
genes, especially on induce apoptosis gene Bax. We also observed an attenuated
effect when MPII was used in combination with chemotherapy drug 5-fluorouracil (5
FU). The mice treated with 5-FU alone did not show a concentration-dependent
effect, but 5-FU in combination with MPII displayed concentration-dependent
effects on liver cancer cells. Our study suggests that MPII works by inducing
apoptosis and cell cycle arrest, and has the potential to be a powerful
anticancer agent.
PMID- 28416330
TI - Delayed responses of subthalamic nucleus to deep brain stimulation in patients
with Parkinson's disease.
PMID- 28416331
TI - A novel inflow cannulation strategy for pediatric mechanical circulatory support
in small left ventricles.
PMID- 28416329
TI - Weight stigma predicts inhibitory control and food selection in response to the
salience of weight discrimination.
AB - OBJECTIVE: Fear and stigmatization are often used to motivate individuals with
higher body weight to engage in healthy behaviors, but these strategies are
sometimes counterproductive, leading to undesirable outcomes. In the present
study, the impact of weight-based stigma on cognition (i.e., inhibitory control)
and food selection (i.e., calories selected) was examined among individuals who
consider themselves to be overweight. It was predicted that participants higher
in perceived weight stigma would perform more poorly on an inhibitory control
task and order more calories on a food selection task when they read about
discrimination against individuals with higher weight versus discrimination
against an out-group. METHODS: Participants completed online prescreen measures
assessing whether they considered themselves to be overweight and their
perceptions of weight stigma. Individuals who considered themselves to be
overweight were invited into the laboratory to complete tasks that manipulated
weight-based discrimination, then inhibitory control and food selection were
measured. RESULTS: The higher participants were in perceived weight stigma, the
more poorly they performed on the inhibitory control task and the more calories
they ordered when they read about discrimination against individuals with higher
body weight. These relationships were not observed when participants read about
discrimination against an out-group. CONCLUSIONS: The present findings provide
evidence that perceptions of weight stigma are critical in understanding the
impact of weight-based discrimination. Additionally, these results have
theoretical and practical implications for both understanding and addressing the
psychological and physical consequences of weight-based stigma.
PMID- 28416327
TI - Executive functioning and substance use in adolescence: Neurobiological and
behavioral perspectives.
AB - The current review is guided by the theoretical perspective that emphasizes the
regulating role of executive functioning (Carver et al., 2009) and presents
studies that elucidate the ways that executive functioning (inhibition and
working memory) explain individual differences in adolescent substance use
independently or by regulating the reactive system (reward and punishment
sensitivity). Behavioral studies indicate that main effects of executive
functioning on adolescent substance use are often nonsignificant or weak in
effect sizes. In contrast, emerging evidence suggests consistent and stronger
regulating effects of executive functioning over reward and punishment
sensitivity. Functional neuroimaging studies reveal significant associations
between executive functioning task-related hemodynamic responses and substance
use with strong effect sizes. There is also direct evidence from studies testing
statistical interactions of the regulating effects of EF-related brain
activation, and indirect evidence in studies examining functional connectivity,
temporal discounting, and reinforced control. We note key future directions and
ways to address limitations in existing work.
PMID- 28416332
TI - The promise of placental power.
PMID- 28416333
TI - Go deep! Benefits of a deep freeze during distal aortic repair.
PMID- 28416334
TI - A systematic approach to improve the outcomes of type A aortic dissection.
AB - OBJECTIVES: The aims of this study are to evaluate the outcomes and trends of
contemporary emergency surgery for acute type A aortic dissection on the basis of
a systematic approach and to assess the impact of temporary aortic crossclamping
during systemic cooling on early and late outcomes. METHODS: We retrospectively
reviewed 702 consecutive patients who underwent emergency surgery for acute type
A aortic dissection between March 2004 and May 2015. Our clinical protocol
includes rapid transfer to the operating room, quick establishment of
cardiopulmonary bypass, temporary aortic crossclamping during cooling, primary
entry resection, and open distal anastomosis. We analyzed the perioperative data,
survival, freedom from aortic reinterventions, and impact of aortic crossclamping
on early and late outcomes. RESULTS: The median time from hospital arrival to
cardiopulmonary bypass establishment was 115 minutes and has decreased over the
last decade (trend test P < .001). We perfused the femoral artery in 615 patients
(87.6%), placed aortic crossclamping in 616 patients (87.7%), and performed open
distal anastomosis in all patients. The operative mortality was 5.4% (38/702),
and the incidence of stroke was 10.8% (76/702). The 7-year overall survival and
freedom from aortic reinterventions were 80.4% and 87.5%, respectively. Compared
with the nonclamping group, the crossclamping group had a shorter operation time,
similar operative mortality, incidence of stroke, and freedom from aortic
reinterventions. CONCLUSIONS: Emergency surgery for acute type A aortic
dissection based on our systematic approach demonstrated excellent early and late
outcomes. The temporary aortic crossclamping during cooling decreased the
operation time without increasing early and late adverse events.
PMID- 28416335
TI - Clinical outcomes following self-expanding metal stent placement for esophageal
salvage.
AB - OBJECTIVES: To assess the efficacy of self-expanding metal stents (SEMS) for
esophageal salvage in patients who would otherwise require esophageal/conduit
resection. METHODS: We performed a retrospective chart review of patients who had
SEMS placed from January 2010 to December 2015. Patient demographics, esophageal
stent characteristics, and outcomes were assessed in our patient cohort. RESULTS:
Our study included a total of 83 patients. A total of 148 SEMS were placed, with
121 partially covered SEMS (pcSEMS) and 27 fully covered SEMS (cSEMS). A stent
was placed more than once in 42.2% of the patients. Median duration of stent
placement was 23 days. Indications for SEMS placement included esophageal leak
after esophageal resection (45.8%), spontaneous esophageal perforation (22.9%),
iatrogenic esophageal perforation (20.5%), and esophageal obstruction (9.6%).
Complications from SEMS placement included 6 stent migrations and 1 esophageal
perforation. Of the 6 stents that migrated, 2 were pcSEMS and 4 were cSEMS. In a
patient who underwent stent placement for a stricture refractory to dilation, a
perforation at the distal end was discovered 2 days after stent removal. The
perforation healed after the second SEMS placement. Ultimately, 15 patients
(18.1%) had to undergo a subsequent esophagectomy or takedown of their conduit
with an overall 81.9% salvage of native esophagus or conduits. CONCLUSIONS: Our
study demonstrates the successful use of SEMS in patients with anastomotic leaks,
perforations, and recalcitrant strictures.
PMID- 28416336
TI - Double trouble or singular success: What can we expect from anatomic correction
of congenitally corrected transposition of the great arteries?
PMID- 28416337
TI - Operating on lungs and thinking on hearts.
PMID- 28416338
TI - Separation and purification of polyphenols from red wine extracts using high
speed counter current chromatography.
AB - Polyphenols are important compounds of red wine owing to their contribution to
sensory properties and antioxidant activities. In this study, high-speed counter
current chromatography (HSCCC) coupled with semi-preparative HPLC was used for
large-scale separation and purification of polyphenols from red wine extracts.
With the solvent system of hexane-ethyl acetate-water (1-50-50), various
oligomeric procyanidins including monomer catechin, epicatechin, dimers B1, B2;
phenolic acids including coutaric acid, caftaric acid and other type of
polyphenols were largely separated within 370min and most of these compounds
presented high yields (0.97mg to 13.79mg) with high purity (90.34% to 98.91%)
after the semi-preparative HPLC isolation. Using the solvent system of Methyl
tert-Butyl Ether (MTBE) - n-butyl alcohol- acetonitrile-water (1-40-1-50,
acidified with 0.01% trifluoroacetic acid (TFA)) by one-step HSCCC of 100mg of
the red wine extracts, the major anthocyanins, i.e., malvidin-3-O-glucoside,
delphinidin-3-O-glucoside and peonidin-3-O-glucoside, as well as two polymeric
proanthocyanidin fractions were successfully separated one another within 320min.
The yields of malvidin-3-O-glucoside, delphinidin-3-O-glucoside and peonidin-3-O
glucoside were 12.12mg, 1.78mg and 11.57mg with the purity of 92.74%, 91.03% and
91.21%, respectively. Thiolysis-UPLC analysis indicated that the two polymeric
proanthocyanidin fractions presented high purity, with mean degree of
polymerization of 7.66+/-0.12 and 6.20+/-0.09, respectively. The further
experiments on the antioxidant activities by DPPH radical test, FRAP assay and
ABTS method showed that all of the isolated procyandins and anthocyanins and the
two polymeric proanthocyanidin fractions, with exception of phenolic acids
possessed much greater antioxidant activities compared to standard Trolox andl
ascorbic acid (2-14 times).
PMID- 28416339
TI - Hemorrhagic cyst of the canal of Nuck after vaginal delivery presenting as a
painful inguinal mass in the early postpartum period.
PMID- 28416340
TI - Use of the Dilapan-S osmotic dilator in missed miscarriage in patients with
severe comorbidities.
PMID- 28416341
TI - The role of cannabinoids in dermatology.
PMID- 28416342
TI - Long-term safety and tolerability of apremilast in patients with psoriasis:
Pooled safety analysis for >=156 weeks from 2 phase 3, randomized, controlled
trials (ESTEEM 1 and 2).
AB - BACKGROUND: Randomized, controlled trials demonstrated efficacy and safety of
apremilast for moderate-to-severe plaque psoriasis and psoriatic arthritis.
OBJECTIVE: Assess long-term safety of oral apremilast in psoriasis patients.
METHODS: Safety findings are reported for 0 to >=156 weeks from the Efficacy and
Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2.
RESULTS: The 0 to >=156-week apremilast-exposure period included 1184 patients
treated twice daily with apremilast 30 mg (1902.2 patient-years). During 0 to
<=52 weeks, the adverse events (AEs) that occurred in >=5% of patients included
diarrhea, nausea, upper respiratory tract infection, nasopharyngitis, tension
headache, and headache. From 0 to >=156 weeks, no new AEs (affecting >=5% of the
population) were reported. AEs, serious AEs, and study drug discontinuations
caused by AEs did not increase with long-term exposure. During the 0 to >=156
week period, the rates of major cardiac events (exposure-adjusted incidence rate
[EAIR] 0.5/100 patient-years), malignancies (EAIR 1.2/100 patient-years),
depression (EAIR 1.8/100 patient-years), or suicide attempts (EAIR 0.1/100
patient-years) did not increase in comparison with the rates found during the 0
to <=52-week period. No serious opportunistic infections, reactivation of
tuberculosis, or clinically meaningful effects on laboratory measurements were
reported. LIMITATIONS: This study had a high dropout rate (21% of patients
ongoing >156 weeks); most were unrelated to safety concerns. CONCLUSIONS:
Apremilast demonstrated an acceptable safety profile and was generally well
tolerated for >=156 weeks.
PMID- 28416343
TI - Pigmented epithelioid melanocytoma (animal-type melanoma): An institutional
experience.
AB - BACKGROUND: Pigmented epithelioid melanocytoma (PEM) is an uncommon, recently
described entity with unknown biologic behavior. There is a high rate of regional
metastases, but limited evidence of distant metastases or disease-related death.
OBJECTIVE: We sought to report our series of patients given a diagnosis of PEM at
our institution and provide mutational analysis of genes commonly implicated in
melanoma in 2 cases. METHODS: The pathology database was queried for cases of PEM
diagnosed at the University of Rochester. Charts were reviewed for follow-up
information. Mutational analysis of melanoma-associated genes was performed on 2
cases. RESULTS: Nine cases of PEM were retrieved in a 10-year retrospective
review. Five patients underwent sentinel lymph node biopsy with 3 of 5 having a
positive sentinel lymph node. All 9 patients are alive and disease-free with
average follow-up of 38.75 months. Two tumors were tested for common melanoma
associated mutations, and were negative, except for a telomerase reverse
transcriptase promoter deletion detected in 1 sample. The deletion has not been
associated with melanoma, and therefore its biologic significance is unclear.
LIMITATIONS: Small sample size, retrospective nature, and single institution
experience are limitations. CONCLUSIONS: PEM appears to have an indolent
behavior. However, currently the evidence is too limited to provide insight into
its true biologic potential.
PMID- 28416344
TI - 25-Hydroxyvitamin-D3 serum modulation after use of sunbeds compliant with
European Union standards: A randomized open observational controlled trial.
AB - BACKGROUND: Regular use of sunbed exposure has been reported to increase 25
hydroxyvitamin-D3 [25(OH)D] serum levels. However, the influence of sunbeds
compliant with the recent European Union standard EN-60335-2-27 on 25(OH)D serum
levels is unknown. OBJECTIVE: We investigated the impact of standard sunbed use
compliant with the European Union standard on 25(OH)D serum modulation and well
being. METHODS: In a randomized controlled study, 25(OH)D serum levels were
measured at enrollment, after 1 week, and after completion of the 12-week period
of sunbed use with twice weekly exposure and compared with the control group
without any sunbed exposure. RESULTS: In the sunbed intervention group (N = 31),
a 27% increase of mean 25(OH)D levels was noted 1 week after starting sunbed use
(P < .01). However, after 12 weeks, mean 25(OH)D levels had declined and were no
longer different from baseline (P = .06). After 12 weeks, 25(OH)D levels did not
differ between the intervention and control group (P = .36). Also the 5-item
World Health Organization Well-Being Index score did not differ between the
sunbed and control groups (P = .19). LIMITATIONS: For ethical reasons recruitment
was limited to persons actively seeking sunbed exposure. CONCLUSIONS: Standard
use of sunbeds compliant with the European Union standard induced a transient
increase of 25(OH)D levels, whereas no change in well-being was observed.
PMID- 28416345
TI - Laryngeal function-preserving operation for T4a laryngeal cancer with vocal cord
paralysis - A case report.
AB - For locally advanced laryngeal cancers, the standard treatment of choice is
chemoradiotherapy if organ function needs to be conserved. Surgical treatment
with larynx preservation is conducted only for limited cases. For locally
advanced laryngeal cancers such as those with vocal cord fixation and/or cricoid
cartilage destruction, there is no apparent standardized organ-preserving surgery
keeping the essential laryngeal functions, viz. the airway, deglutition and
articulation, uncompromized. Recently, our surgical team saw a patient with T4a
advanced laryngeal cancer with vocal cord fixation who aspired to maintain his
laryngeal function. Driven by his eagerness, we contrived novel techniques for
laryngeal function preservation and performed a two-staged operation. In the
first stage, extended vertical partial laryngectomy was conducted including
resection of the affected thyroid, arytenoid, and cricoid cartilages, followed by
local closure of the hypopharynx. Additionally, laryngeal suspension surgery and
cricopharyngeal myotomy were performed in addition to suturing the epiglottis
with the intact arytenoid cartilage to enhance swallowing function. In the second
stage, airway reconstruction was performed using a local skin flap. As of 10
months after operation, there has been no tumor recurrence, and the reconstructed
larynx has been working satisfactorily. In this report we describe an innovative
operation that was especially contrived for laryngeal function preservation.
PMID- 28416346
TI - Bilateral spontaneous symptomatic temporomandibular joint herniation into the
external auditory canal: A case report and literature review.
AB - Spontaneous temporomandibular joint (TMJ) herniation is the entity of protrusion
of the retrodiscal contents of the TMJ into the external auditory canal (EAC)
through a persistent Huschke's foramen. There have been a number of reports of
spontaneous TMJ herniation, but there are no reports of bilateral symptomatic TMJ
herniation. We report a case of a 70-year-old man who complained of a crunching
sound in both ears during mastication. Examination showed bulging from the
anterosuperior wall of the EAC on each side when the patient opened his mouth,
which pushed the tympanic membrane medially. Bony defects in the corresponding
area were seen on computed tomography. We describe a very rare case of bilateral
spontaneous TMJ herniation that caused symptoms by having a direct impact on the
tympanic membrane.
PMID- 28416347
TI - Blood collection vials and clinically used intravenous fluids contain significant
amounts of nitrite.
AB - The biology of the inorganic anion nitrite is linked to nitric oxide (NO) as
nitrite can be reduced to NO and mediate its biological activities. Thus, studies
of nitrite biology require sensitive and selective chemical assays. The acetic
and ascorbic acids method is selective for nitrite and measures it in biological
matrices. However, one of the pitfalls of nitrite measurements is its ubiquitous
presence in sample collection tubes. Here, we showed high levels of nitrite in
collection tubes containing EDTA, sodium citrate or sodium heparin and smaller
amounts in tubes containing lithium heparin or serum clot activator. We also
showed the presence of nitrite in colloid and crystalloid solutions frequently
administered to patients and found variable levels of nitrite in 5% albumin, 0.9%
sodium chloride, lactated ringer's, and dextrose-plus-sodium chloride solutions.
These levels of nitrite varied across lots and manufacturers of the same type of
fluid. Because these fluids are administered intravenously to patients (including
those in shock), sometimes in large volumes (liters), it is possible that
infusions of these nitrite-containing fluids may have clinical implications. A
protocol for blood collection free of nitrite contamination was developed and
used to examine nitrite levels in whole blood, red blood cells, plasma and urine
from normal volunteers. Nitrite measurements were reproducible, had minimal
variability, and did not indicate sex-differences. These findings validated a
method and protocol for selective nitrite assay in biological fluids free of
nitrite contamination which can be applied for study of diseases where
dysfunctional NO signaling has been implicated.
PMID- 28416348
TI - Respiratory function in facioscapulohumeral muscular dystrophy 1.
AB - To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk
factors for developing respiratory insufficiency in facioscapulohumeral muscular
dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1
of varying degrees of severity ranging from ambulatory patients to wheelchair
bound patients. We examined the patients neurologically and by conducting
pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1
second, and static maximal inspiratory and expiratory mouth pressures. We did not
find pulmonary function test abnormalities in ambulant facioscapulohumeral
muscular dystrophy patients. Even though none of the patients complained of
respiratory dysfunction, mild to severe respiratory insufficiency was found in
more than one third of the wheelchair-dependent patients. Maximal inspiratory
pressures and maximal expiratory pressures were decreased in most patients, with
a trend that maximal expiratory pressures were more affected than maximal
inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis
showed the most restricted lung function. Wheelchair-dependent patients with
(kypho-)scoliosis are at risk for developing respiratory function impairment. We
advise examining this group of facioscapulohumeral muscular dystrophy patients
periodically, even in the absence of symptoms of respiratory insufficiency, given
its frequency and impact on daily life and the therapeutic consequences.
PMID- 28416349
TI - Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of
typical nemaline rods.
AB - Mutations in ACTA1 cause a group of myopathies with expanding clinical and
histopathological heterogeneity. We describe three patients with severe ACTA1
related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline
rods. Patient 1 is a five-year-old boy who presented at birth with severe
weakness and respiratory failure, requiring mechanical ventilation. Whole exome
sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation.
Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory
insufficiency at birth requiring mechanical ventilation. Both died at 6 months of
age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by
whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy
can present with muscle morphological findings suggestive of cytoplasmic body
myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in
skeletal muscle sarcomeric alpha-actin may be linked to this histological
appearance. These novel ACTA1 cases also illustrate the successful application of
whole exome sequencing in directly arriving at a candidate genetic diagnosis in
patients with unexpected phenotypic and histologic features for a known
neuromuscular gene.
PMID- 28416351
TI - Intraductal Carcinoma of the Prostate: Anonymous to Ominous.
PMID- 28416350
TI - Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial
Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy.
AB - BACKGROUND: There is increasing low-quality evidence rationalizing the use of
radical therapy for men at high risk of disseminated prostate cancer. OBJECTIVE:
To investigate, using high-quality epidemiologic data, whether initial radical
therapy in men at high risk of disseminated prostate cancer improves survival.
DESIGN, SETTING, AND PARTICIPANTS: An observational population-based Swedish
study from 1996 to 2010 of men at high risk of disseminated prostate cancer
(prostate-specific antigen [PSA] >50) initially treated by radical therapy
(radiation therapy [n=630] or radical prostatectomy [n=120]) or androgen
deprivation therapy (n=17 602), and followed for up to 15 yr. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Prostate-cancer and other-cause mortality
was estimated for the treatment groups. We also matched the two cohorts for
grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and
found androgen deprivation therapy patient matches for 575 of the radical therapy
patients, and then repeated comparative effectiveness analyses. RESULTS AND
LIMITATION: Prostate-cancer mortality was substantially greater in the androgen
deprivation therapy group compared with the radically treated one, in unmatched
(9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched
cohorts, initial androgen deprivation therapy was associated with nearly three
fold higher hazard of prostate-cancer death compared with initial radical therapy
(2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses
suggested that the findings were robust, although the general limitations of
nonrandomized studies remain. Further, the study cohort may have included men
with both systemic and nonsystemic disease, as a sole eligibility criterion of
PSA >50 was used. CONCLUSIONS: This large and comprehensive population-based
study suggests that initial radical therapy in men at high risk of disseminated
prostate cancer improves survival. PATIENT SUMMARY: This large Swedish study
suggests that men with prostate cancer that has spread beyond the prostate
benefit from treating the prostate itself with radiation therapy or surgery
rather than treating the disease with hormones alone.
PMID- 28416352
TI - Setting them up for lifetime activity: Play competence perceptions and physical
activity in young children.
AB - OBJECTIVES: Possessing positive physical perceived competence is important for
physical activity in older children. Young children are primarily physically
active through play-based behaviour rather than through organised sports and
activities, so understanding how play perceptions might influence physical
activity behaviour is important. The study purpose was to assess if perceived
active play competence is associated with young children's physical activity.
DESIGN: Cross sectional study. METHODS: This paper uses two different samples
drawn from the same Australian city, both collected in 2013. The first sample
included 152 children (49% boys) aged 4-5 years (M=4.7, SD=0.47), the second
sample included 78 children (55% boys) aged 5-8 years (M=6.6, SD=0.93). The
Pictorial Scale of Perceived Movement Skill Competence was used to assess
children's perceived competence in six skill-related play activities. Moderate-
to vigorous-intensity physical activity (MVPA) was assessed for 8 consecutive
days via accelerometers. A general linear model with the mean minutes in MVPA per
day as the outcome, perceived play competence as the independent variable and
adjusting for relevant confounders was performed in each sample. RESULTS:
Perceived active play competence was not related to MVPA min/day (B=0.44,
p=0.323) in the younger sample, but was in the older sample (B=1.53, p=0.026),
explaining 24% of adjusted variance. CONCLUSIONS: Positive findings in the older
sample show school-aged children need exposure to play based activities in order
to develop the positive self-perception needed to engage in MVPA every day.
PMID- 28416353
TI - Eating disorders and weight control behaviors change over a collegiate sport
season.
AB - OBJECTIVES: Determine whether the prevalence of eating disorder classifications
(i.e., clinical eating disorder, subclinical eating disorder, and asymptomatic)
and pathogenic weight control behaviors (e.g., bingeing, vomiting) change over a
five-month sport season. DESIGN: Longitudinal study. METHODS: Female collegiate
gymnasts and swimmers (N=325) completed the Questionnaire for Eating Disorder
Diagnoses as well as six items from the Bulimia Test-Revised at Time 1 (two weeks
into the beginning of their athletic season) and Time 2 (final two weeks of the
athletic season); data collections were separated by five months. RESULTS: Over
the course of the season, 90% of the athletes (18 out of 20) retained a clinical
eating disorder diagnosis or moved to the subclinical classification. Of the 83
subclinical athletes at Time 1, 37.3% persisted with that classification and
10.8% developed a clinical eating disorder; the remainder became
asymptomatic/healthy eaters by Time 2. The majority of Time 1 asymptomatic
athletes (92.3%) remained so at Time 2. Exercise and dieting/fasting were the
most frequent forms of weight control behaviors, though each was used less
frequently at Time 2 (exercise=35.4%; dieting=9.2%) than at Time 1
(exercise=42.5%; dieting=12.3%). CONCLUSIONS: Eating disorder classifications,
particularly clinical and subclinical, remain stable across a competitive season,
supporting the need for early detection and purposeful intervention. Athletes
engage in weight control behaviors that may be reinforced in the sport
environment (e.g., supplemental exercise), making identification more challenging
for sports medicine professionals.
PMID- 28416354
TI - Unilateral jumps in different directions: a novel assessment of soccer-associated
power?
AB - OBJECTIVES: We aimed to determine whether countermovement jumps (CMJs; unilateral
and bilateral) performed in different directions assessed independent lower-limb
power qualities, and if unilateral CMJs would better differentiate between elite
and non-elite soccer players than the bilateral vertical (BV) CMJ. DESIGN: Elite
(n=23; age, 18.1+/-1.0years) and non-elite (n=20; age, 22.3+/-2.7years) soccer
players performed three BV, unilateral vertical (UV), unilateral horizontal
forward (UH) and unilateral medial (UM) CMJs. METHODS: Jump performance (height
and projectile range), kinetic and kinematic variables from ground reaction
forces, and peak activation levels of the vastus lateralis and biceps femoris
(BF) muscles from surface electromyography, were compared between jumps and
groups of players. RESULTS: Peak vertical power (V-power) was greater in BV
(220.2+/-30.1W/kg) compared to UV (144.1+/-16.2W/kg), which was greater than UH
(86.7+/-18.3W/kg) and UM (85.5+/-13.5W/kg) (all, p<0.05) but there was no
difference between UH and UM (p=1.000). Peak BF EMG was greater in UH compared to
all other CMJs (p<=0.001). V-power was greater in elite than non-elite for all
CMJs (p<=0.032) except for BV (p=0.197). Elite achieved greater UH projectile
range than non-elite (51.6+/-15.4 vs. 40.4+/-10.4cm, p=0.009). CONCLUSIONS: We
have shown that UH, UV and UM CMJs assess distinct lower-limb muscular power
capabilities in soccer players. Furthermore, as elite players outperformed non
elite players during unilateral but not BV CMJs, unilateral CMJs in different
directions should be included in soccer-specific muscular power assessment and
talent identification protocols, rather than the BV CMJ.
PMID- 28416355
TI - Expression of coproporphyrinogen oxidase is associated with detection of upper
gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic
diagnosis.
AB - BACKGROUND: 5-Aminolevulinic acid is a precursor of photosensitizing
protoporphyrin IX and has been applied for photodynamic diagnosis of brain and
bladder tumors with few side effects. Although most upper gastrointestinal tumors
can be detected during photodynamic diagnosis, some tumors containing signet-ring
cells cannot be visualized. Here, we aimed to assess whether proteins involved in
the absorbance, activation, and turnover of protoporphyrin IX altered the
fluorescence signal in gastric cancer. METHODS: Aminolevulinic acid-mediated
photodynamic diagnosis was performed in 23 lesions from 20 patients using an
endoscope equipped with a blue laser light that caused red fluorescence emission
of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was
assessed during photodynamic diagnosis procedures. Lesions were resected by
endoscopic and/or laparoscopic surgery, and specimens were immunostained and
assessed for the expression of ATP-binding cassette sub-family G member 2,
oligopeptide transporter-1, and coproporphyrinogen oxidase. RESULTS: Photodynamic
diagnosis was negative in four cases (17.4%). Three cases of photodynamic
diagnosis-negative lesions were signet-ring cell carcinomas, and only one case
was differentiated adenocarcinoma (intestinal type). Twenty intestinal type,
photodynamic diagnosis-positive lesions showed high expression of
coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all
negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in
tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression
tended to be higher in luminal surface tumors than in intestinal type tumors.
CONCLUSION: Aminolevulinic acid-mediated photodynamic diagnosis provided good
detection of upper gastrointestinal tumors of intestinal type but not diffuse
type tumors, such as signet-ring cell carcinomas, possibly owing to
coproporphyrinogen oxidase expression.
PMID- 28416356
TI - Risk factors for free flap failure: a retrospective analysis of 881 free flaps
for head and neck defect reconstruction.
AB - The aim of this study was to identify the risk factors for free flap failure
after head and neck reconstructive surgery. The data of 881 consecutive patients
who underwent free flap surgery at the Department of Oral and Maxillofacial
Surgery, Peking University School and Hospital of Stomatology, between January
2013 and November 2016, were reviewed retrospectively. All surgeries were
performed by a single head and neck surgical team. Patient demographic and
surgical data that may have an influence on free flap outcomes were recorded. The
chi2 test and multivariate logistic regression analysis were used to identify
relevant risk factors. In total, 881 free tissue transfer surgeries were included
in this study. Free flap failure occurred in 26 of 881 flaps (2.9%). A history of
irradiation (odds ratio 0.205, 95% confidence interval 0.07-0.56; P=0.002) was a
statistically significant risk factor for free flap failure. Age, diabetes
mellitus, history of previous neck surgery to the anastomosis side, donor site,
choice of recipient vein, use of a coupler device, and postoperative
anticoagulation were not associated with free flap outcomes. Thus, it is
concluded that when performing head and neck reconstructive surgery, special
attention should be paid to patients who have previously undergone irradiation.
PMID- 28416357
TI - Complicated diverticular disease: Position statement on outpatient management,
Hartmann's procedure, laparoscopic peritoneal lavage and laparoscopic approach.
Consensus document of the Spanish Association of Coloproctology and the
Coloproctology Section of the Spanish Association of Surgeons.
AB - The Spanish Association of Coloproctology (AECP) and the Coloproctology Section
of the Spanish Association of Surgeons (AEC), propose this consensus document
about complicated diverticular disease that could be used for decision-making.
Outpatient management, Hartmann's procedure, laparoscopic peritoneal lavage, and
the role of a laparoscopic approach in colonic resection are exposed.
PMID- 28416358
TI - Non-gated high-pitch computed tomography aortic angiography: Myocardial perfusion
defects in patients with suspected aortic dissection.
AB - OBJECTIVES: To investigate the diagnostic value of first-pass myocardial
perfusion defects visualised in non-gated high-pitch computed tomography
angiography (CTA) in patients admitted to the emergency department (ED) for
suspected aortic dissection. METHODS: We recruited 174 ED patients who underwent
high-pitch CTA of the aorta because of suspected aortic dissection. We divided
these patients into two groups (diseased and control groups) based on whether
their clinical data fulfilled the third universal definition of acute myocardial
infarction (AMI), specifically an increase in cardiac troponin (cTn) with at
least one of the following: (a) symptoms of ischemia; (b) new ST-segment-T wave
(ST-T) changes or new left bundle branch block (LBBB); (c) development of
pathological Q wave; (d) new loss of viable myocardium or new regional wall
motion abnormality; or (e) identification of an intracoronary thrombus by
angiography or autopsy. Twenty-two patients with a clinical diagnosis of AMI were
placed in the diseased group. Myocardial perfusion defects were evaluated
qualitatively and quantitatively on the late arterial phase obtained 50 s post
threshold. RESULTS: Of the 22 patients with a final diagnosis of AMI, visually
identifiable perfusion defects were observed in 12 patients. The sensitivity,
specificity, negative predictive value, and positive predictive value of any
perfusion defect for predicting AMI were 54.6%, 94.7%, 93.5%, and 60.0%,
respectively. Quantitative analysis indicated that CT attenuation was
significantly lower within perfusion defects than within the normal myocardium
(67.6 +/- 29.5 HU vs. 92.2 +/- 19.7 HU; p < 0.001). CONCLUSIONS: In patients with
acute chest pain, the presence of myocardial perfusion defect observed on
nongated high-pitch CTA of the aorta can be used to identify individuals with AMI
with high specificity, but low sensitivity.
PMID- 28416359
TI - Marital status is an independent prognostic factor for pancreatic neuroendocrine
tumors patients: An analysis of the Surveillance, Epidemiology, and End Results
(SEER) database.
AB - BACKGROUND AND OBJECTIVES: Marital status's prognostic impact on pancreatic
neuroendocrine tumors (PNET) has not been rigorously studied. We aimed to explore
the relationship between marital status and outcomes of PNET. METHODS: We
retrospectively investigated 2060 PNET cases between 2004 and 2010 from
Surveillance, Epidemiology, and End Results (SEER) database. Variables were
compared by Chi2 test, t-test as appropriate. Kaplan-Meier methods and COX
proportional hazard models were used to ascertain independent prognostic factors.
RESULTS: Married patients had better 5-year overall survival (OS) (53.37% vs.
42.27%, P<0.001) and 5-year pancreatic neuroendocrine tumor specific survival
(PNSS) (67.76% vs. 59.82%, P=0.001) comparing with unmarried patients.
Multivariate analysis revealed marital status is an independent prognostic
factor, with married patients showing better OS (HR=0.74; 95% CI: 0.65-0.84;
P<0.001) and PNSS (HR=0.78; 95% CI: 0.66-0.92; P=0.004). Subgroup analysis
suggested marital status plays a more important role in the PNET patients with
distant stage rather than regional or localized disease. CONCLUSIONS: Marital
status is an independent prognostic factor for survival in PNET patients. Poor
prognosis in unmarried patients may be associated with a delayed diagnosis with
advanced tumor stage, psychosocial and socioeconomic factors. Further studies are
needed.
PMID- 28416360
TI - Primary hepatic angiosarcoma and liver transplantation: Radiological, surgical,
histological findings and clinical outcome.
AB - Angiosarcoma is a rare type of soft tissue sarcoma that accounts for less than 1%
of all sarcomas and only 2% of all primary hepatic tumours. Thorotrast, arsenic,
and vinyl chloride monomer are frequently listed as occupational exposure risks.
The estimated latency is long (10-40 years) in occupational cases and very long
(60 years or more) in non-occupational cases. The symptoms and CT-scan appearance
of hepatic angiosarcoma (HAS) are non-specific. We present a case of a 65-year
old Caucasian male with history of cryptogenic cirrhosis, low alpha-foetoprotein
levels and a single, 4-cm nodule of potential atypical hepatocellular carcinoma
(no washout at MRI and CT-scan) in segment VIII. Laparoscopic radiofrequency
ablation (a biopsy of the neoplastic lesion was technically impossible) was
performed, followed by liver transplantation (LT) 6 months later. High-grade
multifocal HAS was found in the explanted liver, with extensive involvement of
the venous portal structures. No complications were observed during the
postoperative course, and initial immunosuppression included tacrolimus,
mycophenolate mofetil and corticosteroids. Because of the histological findings,
tacrolimus was switched to everolimus as the main immunosuppressive drug one
month after LT. Despite this conversion, the patient developed bone metastases 3
months after LT and peritoneal carcinosis one month later. This case report
suggests that everolimus conversion does not inhibit the development of tumour
metastases. Consequently, HAS remains an absolute contraindication to LT because
of the poor outcome. If LT has been performed for incidental HAS, new molecular
therapies (e.g. vascular endothelial growth factor antagonists) should be
considered immediately after LT to improve the outcome.
PMID- 28416362
TI - In situ targeted activation of an anticancer agent using ultrasound-triggered
release of composite droplets.
AB - The efficiency of a drug is usually highly dependent on the way it is
administered or delivered. As such, targeted-therapy, which requires conceiving
drug-delivery vehicles that will change their state from a relatively stable
structure with a very slow leak-rate to an unstable structure with a fast
release, clearly improves the pharmacokinetics, the absorption, the distribution,
the metabolism and the therapeutic index of a given drug. In this context, we
have developed a particularly effective double stimuli-responsive drug-delivery
method allowing an ultrasound-induced release of a monomethylauristatin E
glucuronide prodrug and its subsequent activation by a beta-glucuronidase. This
led to an increase of cytotoxicity of about 80% on cancer cells.
PMID- 28416361
TI - Unraveling the Regulation of Hepatic Metabolism by Insulin.
AB - During insulin-resistant states such as type 2 diabetes mellitus (T2DM), insulin
fails to suppress hepatic glucose production but promotes lipid synthesis leading
to hyperglycemia and hypertriglyceridemia. Defining the downstream signaling
pathways underlying the control of hepatic metabolism by insulin is necessary for
understanding both normal physiology and the pathogenesis of metabolic disease.
We summarize recent literature highlighting the importance of both hepatic and
extrahepatic mechanisms in insulin regulation of liver glucose and lipid
metabolism. We posit that a failure of insulin to inappropriately regulate liver
metabolism during T2DM is not exclusively from an inherent defect in canonical
liver insulin signaling but is instead due to a combination of hyperinsulinemia,
altered substrate supply, and the input of several extrahepatic signals.
PMID- 28416363
TI - [Adequacy of treatment for osteoporosis in primary prevention. Quantitative and
qualitative study].
AB - OBJECTIVE: Quantitative study: To assess the prevalence of inadequacy of
treatment for osteoporosis in primary prevention (OPP) in women aged 60-74years.
Qualitative study: To evaluate the diagnostic and treatment criteria of the OPP
and it's variability in primary care physicians (PC) and specialists. MATERIAL
AND METHODS: Quantitative study: observational, cross-sectional and retrospective
study. POPULATION: women aged 60-74years with active treatment for OPP (n=424) in
May 2012. Inadequacy if they had <=2 risk factors with a DXA or DXA T-score >=
2.4. Qualitative study: Delphi technique (15items) and two rounds of
consultation. PERIOD: March-April 2014. POPULATION: PC physicians,
rheumatologists and orthopaedic surgeons (n=251). Random sampling. RESULTS:
Quantitative study: degree of inadequacy is 63.4%. In 43.2% isn't mention a
diagnosis of osteoporosis. In 82.3% there isn't mention of risk factors.
TREATMENT: bisphosphonate 40.3% and calcium +vitaminD 47.9%. Qualitative study:
23% respond to the first round, and of these 67% the second round. Items with
higher agreement were the important of the evaluation of risk factors for
diagnosis and bisphosphonates for treatment. Items with fewer consensuses were
using the FRAX and densitometry and treatment with only calcium +vitaminD.
CONCLUSIONS: The percentage of inadequacy is high. The degree of registration in
medical history is low. The Delphi method is useful for detecting discrepancies
between recommendations of clinical practice guidelines and results.
PMID- 28416364
TI - [Implementation of nurse demand managment in primary health care service
providers in Catalonia].
AB - OBJECTIVE: To describe and analyse the implementaction of nurse demand managment
(NDM) among health care providers in Catalonia from 2005 to 2014. DESIGN: Cross
sectional survey. Participants All service providers in Catalonia (n=37). Main
measurements Interviews with nurse manager of each health care provides about ht
barriers and facilitators concerning NDM. Facilitators and barriers were
classified into 3 types: (i)health professional (competence, attitudes,
motivation for change and individual characteristics); (ii)social context
(patients and companions), and (iii)system related factors (organization and
structure, economic incentives). RESULTS: Of the 37 providers, 26 (70.3%) have
implemented the Demand Management Nurse (NDM). The main barriers identified are
the nurse prescriptin regulation, lack of knowledge and skills of nurses, and the
lack of protocols at the start of implantation. Among the facilitators are the
specific training of professionals, a higher ratio of nurses to doctors,
consensus circuits with all professionals and linking the implementation of NDM
to economic incentives. DISCUSSION: NDM is consolidated in Catalonia. However,
the NDM should be included in the curricula of nursing degree and continuing
education programs in primary care teams.
PMID- 28416365
TI - [Increase in the number of diagnosed cases of whooping cough; Do we think more in
it?]
PMID- 28416366
TI - 2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase
4 inhibitor for atopic dermatitis.
AB - BACKGROUND: Crisaborole is a novel, topical nonsteroidal, anti-inflammatory,
phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic
dermatitis. OBJECTIVE: As part of a nonclinical safety testing program, these 2
year studies tested the carcinogenic potential of crisaborole. METHODS:
Crisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice,
and crisaborole was administered orally to rats at doses of 30, 100, or
300mg/kg/day for up to 104 weeks. Systemic exposure to crisaborole and its
metabolites, moribundity/death, clinical signs, and tumor formation were assessed
in each study. RESULTS: Crisaborole treatment was not tumorigenic in mice at any
of the doses administered and did not increase the incidence of neoplastic or
nonneoplastic microscopic lesions compared with controls. Oral administration of
crisaborole at the high dose (300mg/kg/day) to female rats increased the
incidence of treatment-related benign granular cell tumors in the distal
reproductive tract (uterus with cervix and vagina) but did not cause
moribundity/death. CONCLUSION: Crisaborole was well tolerated and not tumorigenic
in mice. It was not tumorigenic in male rats at 300mg/kg/day at exposures that
were 3* the human area under the concentration-time curve (AUC24) and was
nontumorigenic in female rats at 100mg/kg/day at exposures that were 1* the human
AUC24.
PMID- 28416367
TI - Serum Galanin Concentration is Increased in Subjects with Impaired Glucose
Tolerance.
AB - OBJECTIVES: Although extensive data have shown that galanin can regulate the food
intake and glucose metabolism of animals, little is known regarding the galanin
concentration in patients with impaired glucose tolerance (IGT). Therefore, the
aims of this study were to investigate whether serum galanin levels and other
metabolic parameters are changed in patients with IGT compared with controls with
normal glucose tolerance (NGT). METHODS: Data regarding serum galanin levels and
relative metabolic parameters were collected in 12 patients with IGT and 12
healthy patients with NGT. RESULTS: At 1 hour and 2 hours after dinner, serum
galanin, insulin and glucose levels were significantly higher in patients with
IGT than in controls with NGT. Additionally, the body weights of patients with
IGT was higher than those of the controls. Furthermore, a negative correlation
was found between galanin levels and 1-hour glucose concentrations (r=-0.580;
p=0.048) in patients with IGT. CONCLUSIONS: The higher serum galanin levels as
well as the negative correlation between galanin levels and 1-hour glucose
content in patients with IGT may result from the interaction between insulin and
galanin in differing conditions, suggesting that the galanin level may be used as
a potential biomarker for the prediction of IGT in clinical settings.
PMID- 28416368
TI - Nutritional management in women with polycystic ovary syndrome: A review study.
AB - Polycystic ovary syndrome (PCOS) is endocrine disorder in women of reproductive
age, which leads to reproductive, hormonal and metabolic abnormalities. Due to
the presence of insulin resistance, PCOS increases the risk of chronic diseases
like type 2 diabetes, hypertension, lipid disorders, cardiovascular diseases and
malignancies such as breast and endometrial cancer. The actual cause of this
syndrome is unknown but environmental factors such as dietary habits play an
important role in prevention and treatment and lifestyle modifications are the
most important therapeutic strategies in these patients. The approach of the diet
therapy in these patients must be to reach specific goals such as improving
insulin resistance, metabolic and reproductive functions that will be possible
through the design of low-calorie diet to achieve weight loss or maintaining a
healthy weight, limit the intake of simple sugars and refined carbohydrates and
intake foods with a low glycemic index, reduction of saturated and trans fatty
acids and attention to possible deficiencies such as vitamin D, chromium and
omega-3. Given the prevalence of overweight and obesity and insulin resistance, a
relatively low reduction in weight, about 5%, can improve problems such as
insulin resistance, high levels of androgens, reproductive system dysfunctions
and fertility in these women.
PMID- 28416370
TI - Editorial overview: Genome studies and molecular genetics.
PMID- 28416369
TI - Plasma levels of Apolipoprotein A1 and Lecithin:Cholesterol Acyltransferase in
type 2 diabetes mellitus: Correlations with haptoglobin phenotypes.
AB - BACKGROUND: Previous studies have demonstrated that hemoglobin-haptoglobin (Hb
Hp) complex plays a role in developing vascular complications in type 2 diabetes
mellitus (T2DM). The complexes bind with Apolipoprotein A1 (ApoA1) of high
density lipoprotein (HDL), affecting the function of Lecithin:Cholesterol
Acyltransferase (LCAT), and impairing the reverse cholesterol transport mechanism
(RCT). This study investigated the influence of Hp phenotypes on serum levels of
ApoA1 and LCAT in patients with T2DM. METHODS: The study comprised 131 T2DM
patients and 111 matching healthy controls. Fasting blood glucose, HbA1C, and
lipid profile were determined by chemistry autoanalyzer, LCAT and ApoA1 by ELISA,
and Hp phenotypes by gel electrophoresis. RESULTS: Irrespective of Hp phenotypes,
fasting blood glucose, HbA1C, and lipid profile were significantly higher in
patients than in controls, while HDL-cholesterol, ApoA1, and LCAT were lower.
ApoA1 correlated positively with LCAT (r=0.223, p=0.024) and HDL-cholesterol
(r=0.255, 0.003) in patients only. When Hp polymorphism was taken into account,
the levels of LCAT and ApoA1 were significantly lower in patients with Hp2-2 than
that in patients of Hp1-1 and/or Hp2-1. Correlations between ApoA1 and each of
HDL-cholesterol and LCAT (r=0.239, p=0.046, and r=0.252, p=0.040, respectively)
were also observed, but only in patients with Hp2-2 phenotype. CONCLUSIONS: The
reduced levels of LCAT and ApoA1 observed in this study support the suggestion
that T2DM patients with Hp2-2 phenotype could have altered RCT mechanism and
increased risk of developing cardiovascular disease.
PMID- 28416371
TI - Modulation by NADPH oxidase of the chronic cardiovascular and autonomic
interaction between cyclosporine and NSAIDs in female rats.
AB - Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used
together to manage arthritic disorders with an immune component. Previous reports
showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations
in blood pressure. Both effects were ameliorated or exaggerated after selective
cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we
investigated: (i) the interaction of CSA with NSAIDs possessing variable
COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac
autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho
kinase (ROCK) pathway in the interaction. Female rats were pre-instrumented with
femoral catheters and treated for 10 days with CSA (25mg/kg/day), diclofenac
(nonselective NSAIDs, 1mg/kg/day), celecoxib (COX2 inhibitor, 10mg/kg/day), or
their combinations. CSA-mediated hypertension was maintained upon co
administration of either NSAID whereas the concomitant reductions in time- and
frequency-domain indices of heart rate variability (HRV) were accentuated in
presence of diclofenac but not celecoxib. The isovolumic relaxation time (Tauau),
a measure of diastolic function, was reduced by all regimens whereas LV
contractility (dP/dtmax) remained unaffected. The CSA/diclofenac regimen, but not
individual treatments, increased cardiac NOX2 expression and caused more cardiac
structural damage. The inhibition of NOX by diphenyleneiodonium reversed
CSA/diclofenac-evoked increases in MAP, decreases in HRV and Tau, cardiac
structural damage, and increased NOX2 expression. No such effects were observed
after ROCK inhibition by fasudil, despite concomitant decreases in NOX2
expression. In conclusion, CSA/diclofenac-treated female rats exhibit exacerbated
hemodynamic, autonomic, LV, and histopathologic disturbances via ROCK-independent
NOX2 upregulation.
PMID- 28416372
TI - Effects of bilobalide, ginkgolide B and picrotoxinin on GABAA receptor modulation
by structurally diverse positive modulators.
AB - Anxiolytics and anticonvulsants generally positively modulate the action of GABA,
whereas many convulsants (including the chloride channel blocker picrotoxinin)
negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin,
bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been
shown to negatively modulate the action of GABA at alpha1beta2gamma2L GABAA
receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not
known to cause convulsions. We have assessed the action of bilobalide, ginkgolide
B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole,
propofol, thiopentone sodium, diazepam, and allopregnanolone), using two
electrode voltage clamp electrophysiology at recombinant alpha1beta2gamma2L GABAA
receptors expressed in Xenopus oocytes. The results indicate that bilobalide and
ginkgolide B differ from picrotoxinin in their ability to inhibit the actions of
a range of these structurally diverse GABAA positive modulators consistent with
these modulators acting on a multiplicity of active sites associated with GABAA
receptors. In the presence GABA, ginkgolide B was more potent than bilobalide in
inhibiting the GABA-potentiating effect of propofol, equipotent against
loreclezole and allopregnanolone, and less potent against etomidate, diazepam,
and thiopentone sodium. This indicates that in comparison to picrotoxinin,
bilobalide and ginkgolide B differ in their effects on the different modulators.
PMID- 28416373
TI - Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice.
AB - This study aimed to evaluate the inhibitory effects and explore mechanisms of
chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH)
in mice. Benign prostatic hyperplasia model was induced in experimental groups by
daily subcutaneous injections of testosterone propionate (7.5mg/kg/d)
consecutively for 14 d. A total of 60 mice were randomly divided into six groups:
(Group 1) normal control group, (Group 2) benign prostatic hyperplasia model
control group, (Group 3) benign prostatic hyperplasia mice treated with
finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice
treated with chlorogenic acid at dose levels of 0.8mg/kg (low dose group), (Group
5) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels
of 1.6mg/kg (medium dose group) and (Group 6) benign prostatic hyperplasia mice
treated with chlorogenic acid at dose levels of 3.2mg/kg (high dose group).
Animals were sacrificed on the scheduled termination, pick out the eyeball to get
blood, then prostates were weighed and prostatic index were determined. Then the
serum acid phosphatase (ACP), prostatic acid phosphatase (PACP) and typeII5-alpha
reductase (SRD5A2) levels were measured and observed morphological changes of the
prostate. Comparing with benign prostatic hyperplasia model group, the high and
medium dose of chlorogenic acid could significantly reduce prostate index and
levels of acid phosphatase, prostatic acid phosphatase and typeII5-alpha
reductase (P<0.05 or P<0.01). These findings were supported by histopathological
observations of prostate tissues. Histopathological examination also indicated
that chlorogenic acid treatment at the high and medium doses inhibited
testosterone-induced prostatic hyperplasia. The results indicated that
chlorogenic acid exhibited restraining effect on benign prostatic hyperplasia
model animals, and its mechanism might be related to inhibit typeII5-alpha
reductase activity.
PMID- 28416374
TI - Comparing Originator Biologics and Biosimilars: A Review of the Relevant Issues.
AB - PURPOSE: We provide a review of current knowledge on comparability between
biosimilars and originator biologics in view of the continuous evolution
occurring in this highly dynamic area. METHODS: English-language literature
indexed in MEDLINE was explored, without time limits, to July 31, 2016, using the
terms biosimilar, biotechnologic drug, biologic drug, monoclonal antibody, fusion
protein, and anti-tumor necrosis factor. The reference lists of identified
articles were examined carefully for additional pertinent publications. FINDINGS:
Biological medicines are much more structurally complex and extremely sensitive
to manufacturing conditions and therefore more difficult to characterize and
produce than small molecule drugs. Even minor changes in manufacturing may lead
to significant variations of the cellular systems used for biological production,
as well as to differences in the structure, stability, or other quality aspects
of the end product, all of which have the potential to affect tolerability and/or
efficacy and increase the risk of immune responses. Owing to these issues,
specific regulatory guidance on biosimilars is continuously evolving, and there
is some disagreement on which studies need to be implemented to approve a
biosimilar. According to current literature, the following points on biosimilars
deserve consideration: biosimilar development is characterized by global
harmonization, although several not fully answered questions remain regarding
extrapolation of indications, switching or interchangeability, and tolerability;
in patients with rheumatic diseases, the tolerability and efficacy of biosimilars
in clinical practice remain to be established; several medical and patient
associations have published position papers on biosimilars requesting that
safety, efficacy, and traceability be carefully considered; long-term
postmarketing studies should be implemented to allow physicians to gain
confidence in biosimilars. IMPLICATIONS: On the basis of current knowledge, and
taking into consideration both regulatory rules and medical society positions, it
can be concluded that, although cost savings are highly desirable, the approval
process for biosimilars needs to place tolerability and efficacy, supported by
scientifically sound evidence, as the highest priority. Moreover, physicians must
retain full authority regarding the decision about which biopharmaceutical to use
for treating patients.
PMID- 28416375
TI - Automatic and manual Doppler velocimetry measurements of the uterine artery in
pregnant ewes.
AB - We aimed to compare measurements of speed and blood flow parameters obtained
manually and automatically in the uterine arteries of pregnant ewes. Eighteen
Santa Ines ewes, confirmed to be pregnant, were followed every 2 weeks until
parturition. The systolic peak (PS), end diastolic velocity (ED), maximum and
average speed in the cardiac cycle (TAMAX and TAMEAN, respectively), pulsatility
index (PI), resistance index (RI) and the systole/diastole (S/D) ratio and body
flow volume (BFV) was measured. We began the wave evaluation automatically, then
the observer manually marked the beginning and end of the wave. To determine the
differences between manual and automatic methods, a t-test was used for each of
the study variables (PS, ED, TAMAX, TAMEAN, PI, RI, S/D, and BFV), with p<0.05
considered significant. Both methods were found to be effective for producing
estimates for the variables analyzed. With the exception of the IP, IR and S/D
(p<0.05), no significant differences were found between the methods. The manual
method underestimated the PI (1.00+/-0.21*1.04+/-0.20), S/D (2.51+/-0.43*2.40+/
0.44) and RI (0.57+/-0.07*0.59+/-0.07) compared with the automatic method
(p<0.05). The weakest correlations between methods were identified for the PI, RI
and S/D variables (p<0.001). Manual evaluation allowed more accurate
identification of the beginning and end of the systole and diastole, which may
influence the outcome of some variables.
PMID- 28416376
TI - Seminal plasma removal by density-gradient centrifugation is superior for goat
sperm preservation compared with classical sperm washing.
AB - Seminal plasma removal is routine in goat sperm cryopreservation protocols. The
classical washing procedure designed to accomplish this usually leaves the pellet
resulting from use of this procedure contaminated with dead sperm, debris, and
cells other than sperm. This contamination negatively affects viability of sperm
after cryopreservation. The present research was conducted to compare the effect
on chilled and frozen-thawed goat sperm of the classical washing method to that
of a selective washing method involving density gradient centrifugation (DGC). In
the first experiment, sperm variables were measured in freshly collected sperm,
and again after its washing with both methods and chilling at 5 degrees C for 0,
3, 24, 48, 72 or 96h. The DGC-washed sperm had greater (P<0.01) straight line
velocity (VSL), average path velocity (VAP) and progression ratio values at all
chilling times. The amplitude of lateral head displacement (ALH) was, however,
less (P<0.001) in the DGC-washed sperm at all chilling times. There was a
negative correlation (P<0.05) between ALH and VSL. In the second experiment
involving the freezing-thawing of sperm washed by using either method, aliquots
were post-wash diluted with a Tris-citric acid/glucose/egg yolk/glycerol-based
medium and frozen in liquid nitrogen for 5days. After thawing, neither the VCL,
VSL nor VAP of the DGC-washed samples were affected, whereas the traditionally
washed samples had less motility. In conclusion, the use of DGC was associated
with enhanced sperm motility variables after chilling and freezing-thawing. This
procedure would, therefore, be a useful means of removing seminal plasma from
goat semen and obtaining greater quality sperm for insemination purposes.
PMID- 28416377
TI - Comparison between two estradiol-progesterone based protocols for timed
artificial insemination in blocks in lactating Nelore cows.
AB - The aim of this study was to compare the use of artificial insemination in time
blocks (Artificial Insemination Blocks, AIB) using an 8 and 9 d estradiol
progesterone based protocol. In this experiment, lactating Nelore cows (n=253)
were subjected to two estradiol-progesterone based TAI protocols. On the morning
of Day 10 (8d group, n=124) or Day 11 (9d group, n=129), cows were examined by
ultrasonography to evaluate the diameter of the preovulatory follicle and were
inseminated once at one of the following time points, according to the diameter
of the pre-ovulatory follicle (POF): Block 0 (POF>=15mm, TAI 0h after
conventional TAI), Block 1 (POF 13.0-14.9mm, TAI 6h later), Block 2 (POF 10.1
12.9mm, TAI 24h later), and Block 3 (POF<=10.0mm, TAI 30h later). The pregnancy
per AI (P/AI) did not differ between 8d and 9d groups (P>0.05). Considering only
multiparous cows, however, P/AI tended to be greater in the 8d (64.1%) than in
the 9d group (49.3%; P=0.08). Cows from the 9d group tended to have a larger POF
than cows from the 8d group (P=0.07). In conclusion, these results provide
evidence that there is no difference between 8d or 9d protocols when using the
AIB technique. Use of the 8d estradiol-progesterone based protocol, however,
tended to increase pregnancy in multiparous cows.
PMID- 28416378
TI - Risks of contrast media applied via the gastrointestinal route.
PMID- 28416379
TI - Editorial: Feline behavior and cognition.
PMID- 28416380
TI - Spinal dopaminergic involvement in the antihyperalgesic effect of antidepressants
in a rat model of neuropathic pain.
AB - Antidepressants such as tricyclic antidepressants, and serotonin noradrenaline
reuptake inhibitors are a first-line treatment for neuropathic pain. Here, we
aimed to determine the involvement of the spinal dopaminergic system in the
antihyperalgesic effects of antidepressants in a rat model of neuropathic pain
induced by spinal nerve ligation (SNL). The right L5 spinal nerve of male Sprague
Dawley rats was ligated under inhalation anesthesia to induce hyperalgesia.
Behavioral testing was performed by measuring ipsilateral hindpaw withdrawal
thresholds after intraperitoneal injection of amitriptyline, duloxetine,
milnacipran, and fluoxetine. D2-like receptors were blocked by intrathecal
administration of sulpiride. We also determined the concentrations of dopamine in
the spinal cord using microdialysis after injection of antidepressants. The
dopamine contents in the spinal dorsal horn were also measured in normal and SNL
rats at 2, 3, 4, and 8 weeks after SNL surgery. Intraperitoneal injection of
amitriptyline, duloxetine, milnacipran, and fluoxetine (3-30mg/kg) produced
antihyperalgesic effects, and prevented by intrathecal pre-injection of sulpiride
(30MUg). Microdialysis revealed the dopamine levels in the spinal cord were
increased after intraperitoneal injection of each antidepressant (10mg/kg).
Furthermore, the dopamine content in homogenized spinal cord tissue were
increased at 2 weeks after SNL and then subsequently declined. Our results
suggest that the effect of antidepressants against neuropathic pain is related to
modulation of not only noradrenalin and serotonin but also dopamine levels in the
spinal cord.
PMID- 28416381
TI - Potent bactericidal activity of silver nanoparticles synthesized from Cassia
fistula fruit.
AB - We demonstrated one-step synthesis of silver nanoparticles (AgNPs) from Cassia
fistula fruit extract and their antibacterial activity against E. coli and K.
pneumoniae. Biogenic AgNPs were characterized by scanning electron microscopy, X
Ray diffraction and fourier transform infrared spectroscopy. Results confirmed
spherical shaped AgNPs with an average crystallite size of ~69 nm. Dose-dependent
(0, 10, 20, 40 and 80 MUg mL-1) growth kinetic studies showed 100% potency
against E. coli (20 MUg mL-1) and K. pneumoniae (80 MUg mL-1) after 1 and 5 h,
respectively. Surface morphology analysis revealed formation of groove/pits in
the lysed cell membrane that eventually led to bacterial death.
PMID- 28416382
TI - Isolation, pathogenicity and characterization of a novel bacterial pathogen
Streptococcus uberis from diseased mandarin fish Siniperca chuatsi.
AB - In recent years, mandarin fish had a high mortality rate associated with abnormal
swimming, exophthalmia, corneal opacity and eye hemorrhage on a fish farm located
at Foshan city, Guangdong province, China. Three isolates of Gram-positive, chain
forming cocci were recovered from moribund fish, and designated as SS131025-1,
SS131025-2, and SS131025-3. These isolates were identified as Streptococcus
uberis according to their morphologic and physio-biochemical characteristics as
well as phylogenetic analysis based on their 16S rRNA and GapC gene sequences.
The pathogenicity of S. uberis to mandarin fish was determined by challenge
experiments. Results of artificial challenge showed S. uberis infected healthy
mandarin fish and lead to death by eyeball injection or immersion route, and the
LD50 of SS131025-1 with eyeball injection was 2.0 * 106.42 CFU per fish. Moreover
extracellular product (ECP) of the isolated S.uberis induced CPB cell apoptosis
and cause death of mandarin fish. In addition, these S. uberis strains could also
infect tilapia, but not grass carp and crucian carp, and grew in brain-heart
infusion broth with an optimal temperature of 37 degrees C, pH of 7.0, and
salinity of 0%. Antibiotic sensitivity testing indicated that these isolates were
susceptible to rifampicin and furazolidone but resistant to 20 kinds of
antibiotics. Histopathologically, infection with S. uberis could cause serious
pathological changes in brain tissues such as vacuoles in matrix, swollen
mitochondria with lysis of cristae and disintegration, and lots of coccus was
observed both under electron and light microscope. These results shed some light
on the pathogenicity of the isolates and how to prevent and control S. uberis
infection in mandarin fish.
PMID- 28416383
TI - Comparative characterization analysis of synonymous codon usage bias in classical
swine fever virus.
AB - Classical swine fever virus (CSFV) is responsible for the highly contagious viral
disease of swine, and causes great economic loss in the swine-raising industry.
Considering the significance of CSFV, a systemic analysis was performed to study
its codon usage patterns. In this study, using the complete genome sequences of
76 CSFV representing three genotypes, we firstly analyzed the relative nucleotide
composition, effective number of codon (ENC) and synonymous codon usage in CSFV
genomes. The results showed that CSFV is GC-moderate genome and the third-ended
codons are not preferentially used. Every ENC values in CSFV genomes are >50,
indicating that the codon usage bias is comparatively slight. Subsequently, we
performed the correspondence analysis (COA) to investigate synonymous codon usage
variation among all of the CSFV genomes. We found that codon usage bias in these
CSFV genomes is greatly influenced by G + C mutation, which suggests that
mutational pressure may be the main factor determining the codon usage biases.
Moreover, most of the codon usage bias among different CSFV ORFs is directly
related to the nucleotide composition. Other factors, such as hydrophobicity and
aromaticity, also influence the codon usage variation among CSFV genomes. Our
study represents the most comprehensive analysis of codon usage patterns in CSFV
genome and provides a basic understanding of the mechanisms for its codon usage
bias.
PMID- 28416384
TI - Overexpressed HSPA2 correlates with tumor angiogenesis and unfavorable prognosis
in pancreatic carcinoma.
AB - Heat shock-related 70-kDa protein 2 (HSPA2) is known to correlate with tumor
development and progression. This work aimed to determine the expression and
prognostic roles of HSPA2 in pancreatic carcinoma. Tumor and their corresponding
non-tumor tissues were obtained from 80 patients with pancreatic carcinoma. HSPA2
expression in tumor and non-tumor tissues was evaluated by immunohistochemistry.
Expression of vascular endothelial growth factor (VEGF) and CD31 in tumor tissues
were also evaluated by immunostaining. The relationships of HSPA2 with
clinicopathological data, tumor angiogenesis and prognosis were analyzed. The
results showed that HSPA2 expression was significantly elevated in tumor tissues
compared with adjacent non-tumor tissues (P < 0.05). High HSPA2 expression was
significantly associated with aggressive clinicopathological characteristics.
HSPA2 staining was positively correlated with VEGF (r = 0.466, P < 0.001) and
microvessel density (MVD) (r = 0.366, P = 0.001) in tumor tissues. Patients with
high HSPA2 expression showed worse relapse-free survival (RFS) (P < 0.001) and
overall survival (OS) (P < 0.001) than those with low HSPA2 expression.
Multivariate analysis indicated that high HSPA2 expression was an independent
predictor for poor RFS (P < 0.001) and OS (P = 0.001). Taken together,
overexpressed HSPA2 is correlated with tumor angiogenesis and poor prognosis in
pancreatic carcinoma. HSPA2 may play an important role in tumor progression, and
serve as a potential biomarker for the prediction of adverse prognosis in
pancreatic carcinoma.
PMID- 28416385
TI - Abdominal adiposity and low physical activity are independently and inversely
associated with bone mineral density.
AB - BACKGROUND AND METHODS: Obesity is a highly heterogeneous condition, and the link
between adiposity distribution profiles and skeletal health is not well
understood. This study examined the association between adiposity and bone
mineral density (BMD) in a large cohort (5268 individuals) of US adults aged 20
85 years. RESULTS: Body mass index (BMI) and moderate-to-vigorous physical
activity were positively associated with BMD. Conversely, abdominal adiposity was
negatively associated with BMD, even after adjusting for age, race, BMI, and
objectively-measured physical activity. CONCLUSIONS: These findings highlight the
negative influence of abdominal adiposity on BMD and contradict the notion that
excess fat mass is protective for bone health.
PMID- 28416386
TI - Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the
Mycobacterium tuberculosis repressor EthR2.
AB - Inhibition of transcriptional regulators of bacterial pathogens with the aim of
reprogramming their metabolism to modify their antibiotic susceptibility
constitutes a promising therapeutic strategy. One example is the bio-activation
of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by
inhibiting the transcriptional repressor EthR. Recently, we discovered that
inhibition of a second transcriptional repressor, EthR2, leads to the awakening
of a new ethionamide bio-activation pathway. The x-ray structure of EthR2 was
solved at 2.3 A resolution in complex with a compound called SMARt-420 (Small
Molecule Aborting Resistance). Detailed comparison and structural analysis
revealed interesting insights for the upcoming structure-based design of EthR2
inhibitors as an alternative to revert ethionamide resistance in Mycobacterium
tuberculosis.
PMID- 28416387
TI - Differential regulation of the lipoxygenase pathway in shrimp hepatopancreases
and ovaries during ovarian development in the black tiger shrimp Penaeus monodon.
AB - Dietary polyunsaturated fatty acids (PUFAs) are critical to the success of
ovarian development in marine crustaceans, especially for domesticated species
such as the black tiger shrimp Penaeus monodon. These fatty acids are stored in a
midgut gland called the hepatopancreas and subsequently serve as an energy source
or are incorporated in yolk during ovarian development. PUFAs are known
precursors of hydroxy fatty acids, including hydroxyeicosatetraenoic acid and
hydroxyeicosapentaenoic acid (HEPE), which are catalyzed by lipoxygenases (LOX).
In previous studies, 8-HEPE has been shown to regulate female reproduction and
adipogenesis in marine crustaceans. However, whether the biosynthesis of 8-HEPE
in these species is the result of LOX activity has yet to be investigated. In
this study, 8-HEPE was identified exclusively in P. monodon hepatopancreases
using liquid chromatography-mass spectrometry. Treatment with
nordihydroguaiaretic acid resulted in the reduction of 8-HEPE, suggesting the
enzyme-dependent catalysis of 8-HEPE in hepatopancreases. Additionally, a full
length P. monodon LOX (PmLOX) was amplified from shrimp ovary cDNA. Sequence
analysis revealed that the putative PmLOX contains domains and catalytic residues
required for LOX catalytic function. Furthermore, PmLOX expression increased
steadily as shrimp ovary maturation progressed, while PmLOX expression and the
amount of 8-HEPE decreased in shrimp hepatopancreases. These findings not only
suggest differential requirements for hydroxy fatty acid biosynthesis in shrimp
ovaries and hepatopancreases during the P. monodon ovarian development, but also
provide insights into the LOX pathway in marine crustaceans.
PMID- 28416388
TI - Human GRP78 affinity towards its signaling partners Ire1alpha and PERK is
differently modulated by an unfolded protein client.
AB - Protein-folding stress is characteristic of specialized secretory cells and plays
a dominant role in a multitude of diseases. The unfolded protein response (UPR)
thus triggered is a proteostatic signaling network that adapts the protein
folding capacity of the endoplasmic reticulum to the cellular demands. We have
measured the binding affinities between human GRP78, an essential chaperone
located in ER, and two transmembrane UPR sensors (human PERK and Ire1alpha), with
or without the addition of an unfolded protein client. We reveal distinct binding
affinities between the binary and ternary complexes thus formed, that suggest a
preference for the PERK signaling branch under stress, and a predilection for the
GRP78-UPR sensor complex formation upon stressor removal. These results imply a
gated UPR mechanism that tunes the overall cellular behavior to the accumulation
of unfolded proteins.
PMID- 28416390
TI - Fluoroscopy-guided placement of pull-type mushroom-retained gastrostomy tubes in
102 patients.
AB - PURPOSE: The purpose of this study was to evaluate the technical and clinical
results of fluoroscopy-guided placement of pull-type mushroom-retained
gastrostomy tubes. MATERIALS AND METHODS: This retrospective study included 102
patients (61 men, 41 women) with a mean age of 59years+/-16.3 (SD) (range, 18
94years) who had fluoroscopy-guided placement of pull-type mushroom-retained
gastrostomy tubes. All procedures were performed after inflating the stomach with
air via an orally inserted 5-Fr catheter by retrograde catheterization of the
esophagogastric junction. Demographic data, results of the procedures and
complications were evaluated. RESULTS: A technical success was observed in
101/102 patients, yielding a technical success rate of 99%. Complications due to
the procedure were observed in 17/102 patients yielding a procedure-related
complication rate of 16.7%. Procedure-related complications included peristomal
superficial cellulitis (6/102; 5.9%), peristomal abscess (4/102; 3.9%),
subcutaneous hematoma (3/102; 2.9%), peristomal leakage (2/102; 2%), inadvertent
removal of the tube (1/102; 1%) and death due to procedure-related peritonitis
(1/102; 1%). CONCLUSION: Fluoroscopy-guided placement of pull-type mushroom
retained gastrostomy tubes is a feasible and effective method for enteral
nutrition.
PMID- 28416389
TI - Shp1 positively regulates EGFR signaling by controlling EGFR protein expression
in mammary epithelial cells.
AB - SH2-domain containing protein tyrosine phosphatase 1 (Shp1/PTPN6) is mainly
expressed in hematopoietic cells and acts a negative signaling regulator.
Although Shp1 is also expressed in epithelial cells, the function of shp1 in
normal epithelial is still less well understood, especially in regulating the
growth of epithelial cells. In this study, different shRNAs and siRNAs against
Shp1 were used to knockdown Shp1 expression in MCF10A, an immortalized mammary
epithelial cell line. Shp1 knockdown resulted in inhibited cell growth in part
due to lower percentage of MCF10A cells entering into S phase and reduced cyclin
D1 expression. Accordingly, EGF-induced tyrosyl phosphorylation of EGFR and Stat5
was significantly inhibited in cells with Shp1 knockdown compared with control
whereas EGF-induced Akt and Erk phosphorylation was not affected by Shp1
knockdown. Further analysis revealed that Shp1 knockdown lead to decreased EGFR
protein expression without affecting EGFR mRNA expression or increasing EGFR
protein degradation. Our data indicate that Shp1 functions as a positive
regulator and acts in a novel mechanism through promoting EGFR protein expression
in mammary epithelial cells.
PMID- 28416391
TI - Ultrasound Guided Out-of-Plane Versus In-Plane Transpectoral Left Axillary Vein
Cannulation.
AB - OBJECTIVE: The primary objective was to compare the frequency of first-attempt
successful axillary vein cannulation by the Seldinger technique using out-of
plane ultrasound guidance versus in-plane imaging. Between the two ultrasound
imaging planes, this study also compared the number of attempts that were
necessary for the cannulation of the left axillary vein along with the number of
needle redirections that had to be done for final cannulation of the vein.
Incidence of complications and the number of times the procedure was abandoned
also were compared between the two imaging planes. DESIGN: Prospective,
randomized, interventional study. SETTING: Tertiary care cardiac center.
PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Left axillary vein
cannulation under ultrasound guidance by Seldinger technique. MEASUREMENTS AND
MAIN RESULTS: The left axillary vein was accessed under ultrasound guidance in 86
consecutive adult cardiac surgical patients. They were randomized to out-of-plane
(Group I, n = 43) and in-plane (Group II, n = 43) groups. In group I, the number
of first-attempt cannulations was very high (p < 0.01). The number of attempts to
access the vein was significantly lower in this group (p < 0.05). The duration
for completion of the procedure was also less in group I with out-of-plane
ultrasound guidance (p < 0.01). The number of needle redirections and the
incidence of complications (arterial puncture, pneumothorax hematoma formation)
were similar between the groups. There was no difference in the number of times
the procedure was abandoned between the two groups. With an assumption that the
first 10 patients in each group would suffice for overcoming the learning curve,
the above aspects were analyzed further in each group. The first-attempt
cannulation success continued to be significantly higher in the out-of-plane
group. CONCLUSIONS: Out-of-plane ultrasound imaging during axillary vein
cannulation increased the chance of first-attempt successful cannulation.
Axillary vein cannulation under out-of-plane ultrasound imaging also appeared to
be quicker and was preferable in terms of the fewer number of attempts that were
necessary for a successful vein cannulation.
PMID- 28416392
TI - Right Ventricular Function After Cardiac Surgery Is a Strong Independent
Predictor for Long-Term Mortality.
AB - OBJECTIVE: To establish the all-cause mortality of right ventricular dysfunction
after cardiac surgery in a heterogeneous group of cardiac surgery patients.
DESIGN: Retrospective analysis of a heterogeneous group of 1,109 cardiac surgery
patients in a 4-year period. SETTING: Single-center study in a tertiary teaching
hospital. PARTICIPANTS: One thousand one hundred nine cardiac surgery patients.
By protocol, patients were monitored with a pulmonary artery catheter, enabling
continuous right ventricular ejection fraction (RVEF) measurements.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measurements were performed
once per minute for the first 24 postoperative hours and expressed as average
over the complete period. Primary outcome was 2-year all-cause mortality. RVEF
was categorized into 3 subgroups: <20%, 20-30%, and >30%. Median follow-up time
was 739 days. Two-year mortality was significantly different across groups: 4.1%
for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for
patients with RVEF <20%, p < 0.001. Additional risk factors for a poor RVEF were
age, body weight, New York Heart Association class, chronic obstructive pulmonary
disease, poor left ventricular function, and higher risk scores (Acute Physiology
and Chronic Health Evaluation and European System for Cardiac Operative Risk
Evaluation). In a multivariate analysis, RVEF as a continuous variable was
associated independently with the primary outcome (odds ratio 0.95 confidence
interval 0.91-0.99, p = 0.011.) Odds ratios for RVEF <20% were 1.88 (confidence
interval 1.18-3.00, p = 0.008). CONCLUSIONS: Right ventricular function is
associated independently with 2-year all-cause mortality in a heterogenic cardiac
surgery population.
PMID- 28416394
TI - Moderate reagent mixing on an orbital shaker reduces the incubation time of
enzyme-linked immunosorbent assay.
AB - Rapid diagnostic tests can be developed using ELISA for detection of diseases in
emergency conditions. Conventional ELISA takes 1-2 days, making it unsuitable for
rapid diagnostics. Here, we report the effect of reagents mixing via shaking or
vortexing on the assay timing of ELISA. A 48-min protocol of ELISA involving 12
min incubations with reagent mixing at 750 rpm for every step was optimized.
Contrary to this, time-optimized control ELISA performed without mixing produced
similar results in 8 h, leaving a time gain of 7 h using the developed protocol.
Collectively, the findings suggest the development of ELISA-based rapid
diagnostics.
PMID- 28416393
TI - TDP-43 expression influences amyloidbeta plaque deposition and tau aggregation.
AB - Although the main focus in Alzheimer's disease (AD) has been an investigation of
mechanisms causing Abeta plaque deposition and tau tangle formation, recent
studies have shown that phosphorylated TDP-43 pathology is present in up to 50%
of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been
associated with more severe AD pathology. Therefore, we hypothesized that TDP-43
may regulate amyloid-beta precursor protein (APP) trafficking and tau
phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we
developed a transgenic mouse that overexpresses hippocampal and cortical neuronal
TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and
presenilin 1 (PSEN1DeltaE9). In our model, increased TDP-43 was related to
increased tau aggregation as evidenced by thioflavin S-positive phosphorylated
tau, which may implicate TDP-43 expression in pre-tangle formation. In addition,
there was increased endosomal/lysosomal localization of APP and reduced Abeta
plaque formation with increased TDP-43. Furthermore, there was decreased
calcineurin with elevated TDP-43 expression. Since calcineurin is a phosphatase
for TDP-43, the decreased calcineurin expression may be one mechanism leading to
an increase in accumulation of diffuse phosphorylated TDP-43 in the hippocampus
and cortex. We further show that when TDP-43 is knocked down there is an increase
in calcineurin. In our model of selective TDP-43 overexpression in an APP/PSEN1
background, we show that TDP-43 decreases Abeta plaque deposition while
increasing abnormal tau aggregation. These observations indicate that TDP-43 may
play a role in regulating APP trafficking and tau aggregation. Our data suggest
that TDP-43 could be a putative target for therapeutic intervention in AD
affecting both Abeta plaque formation and tauopathy.
PMID- 28416395
TI - The early history of manganese and the recognition of its neurotoxicity, 1837
1936.
AB - The history of the biomedical recognition manganese-caused neurotoxicity mirrors
changing technologies as much as it does the ontology of parkinsonism. The
initial 1837 report of manganese-induced neurologic injury was made by John
Couper, a university-based physician in Scotland. He made clear that the outbreak
occurred among workers at the Charles Tennant bleach manufactory in the environs
of Glasgow. The relatively new technology of chlorine generation using manganese
accounted for the novel exposure involved. At the time, this factory was the
largest hypochlorite bleaching powder producer in the world. As the 19th century
progressed, technological change in steel fabrication requiring higher manganese
content greatly increased demand for the metal. Nonetheless, more than six
decades elapsed before the next reports of manganese neurotoxicity emerged. Two
unrelated outbreaks (both on Continental Europe) were reported within weeks of
each other in 1901, one by von Jaksch and the other by Embden. All the cases were
heavily exposed to manganese-containing dust. By the eve of the First World War,
a total of 9 patients with manganese-caused neurologic illness had been reported
in five separate Continental European publications. Meanwhile, new technology led
to another exposure source. Magnetic separation techniques allowed the extraction
of zinc from mixed ore also containing iron and manganese, leading to
exploitation of a unique source of high manganese-content ore found in New
Jersey. Not long after that technology's introduction, in 1912 Casamajor reported
the first U.S. cases of manganism, detailing classic findings. Additional cases
from the same cohort were reported a few years later, with continued exposure
driven by First World War-driven demand for manganese to be used in armaments.
The nosology of chronic manganese neurotoxicity remained in flux, with
considerable emphasis on shared attributes with Wilson's disease, a syndrome only
then recently described. A landmark 1924 primate study by Mella showed manganese
induced basal ganglion damage; human autopsy study data in the years following
further supported the view that manganese toxicity represented a parkinsonian
syndrome. As the 1937 centenary of Couper's first report approached, newer
technologies (electric arc welding and battery making) were being linked to
manganese-caused disease, even as mineral extraction was expanding as a global
source of exposure.
PMID- 28416396
TI - Chitosan composite three dimensional macrospheric scaffolds for bone tissue
engineering.
AB - The present work deals with the fabrication of chitosan composite scaffolds with
controllable and predictable internal architecture for bone tissue engineering.
Chitosan (CS) based composites were developed by varying montmorillonite (MMT)
and hydroxyapatite (HA) combinations to fabricate macrospheric three dimensional
(3D) scaffolds by direct agglomeration of the sintered macrospheres. The
fabricated CS, CS/MMT, CS/HA and CS/MMT/HA 3D scaffolds were characterized for
their physicochemical, biological and mechanical properties. The XRD and ATR-FTIR
studies confirmed the presence of the individual constituents and the molecular
interaction between them, respectively. The reinforcement with HA and MMT showed
reduced swelling and degradation rate. It was found that in comparison to pure
CS, the CS/HA/MMT composites exhibited improved hemocompatibility and protein
adsorption. The sintering of the macrospheres controlled the swelling ability of
the scaffolds which played an important role in maintaining the mechanical
strength of the 3D scaffolds. The CS/HA/MMT composite scaffold showed 14 folds
increase in the compressive strength when compared to pure CS scaffolds. The
fabricated scaffolds were also found to encourage the MG 63 cell proliferation.
Hence, from the above studies it can be concluded that the CS/HA/MMT composite 3D
macrospheric scaffolds have wider and more practical application in bone tissue
regeneration applications.
PMID- 28416397
TI - Monitoring thermal and chemical unfolding of Brugia malayi calreticulin using
fluorescence and Circular Dichroism spectroscopy.
AB - Calreticulin of Brugia malayi (BmCRT) play very important role in host-parasite
interaction. In previous study it was found that BmCRT is responsible for
prevention of host classical complement pathway activation via its interaction
with first component C1q of the human host. Therefore, BmCRT is an essential
protein for parasite survival and an important drug target to fend filariasis. In
the present study, we have carried out a systamatic biophysical characterization
of BmCRT protein. Unfolding of BmCRT was found to be non-cooperative two-state
process in the presence of both denaturant GdmCl and urea. The results also
illustrated that protein lost its 50% activity at 1.5M GdmCl and 3M Urea.
Partially unfolded and molten-globule like intermediate state was observed at 0.8
to 1.2M GdmCl while Urea unfolding showed intermediate state at 1.2 to 1.6M.
Unfolding pathway monitored with the help of apolar quencher, favor above
observations. All of these findings support the presence of detectable
intermediate state during unfolding pathway of BmCRT. Furthermore, this study
indicates that BmCRT is more stable toward temperature (Tm=65 degrees C), pH and
trypsin digestion. These differences in properties as compared to host can be
fruitfully utilized for synthesis of compounds effective against the parasite.
PMID- 28416398
TI - Synthesis, characterization, and evaluation of poly(aminoethyl) modified chitosan
and its hydrogel used as antibacterial wound dressing.
AB - This study aims to develop new antibacterial hydrogel wound dressings composed of
poly(aminoethyl) modified chitosan (PAEMCS). FTIR, 1H NMR, and elemental analysis
demonstrated that PAEMCS was successfully synthesized via grafting
poly(aminoethyl) groups onto hydroxyl groups on chitin first, and removing acetyl
groups from the grafted polymer afterward. XRD and TGA implied its well-defined
crystallinity and thermostability. Furthermore, a series of hydrogels were
fabricated under the participation of dipotassium hydrogen phosphate (DHP). The
gelation tests suggested that the higher concentration of PAEMCS or DHP was
beneficial to the formation of hydrogels. The pH values of hydrogels at 37
degrees C were all in the range of 7.12-7.50. The rheological tests indicated
that PAEMCS-based hydrogels were of lower DHP addition and higher elasticity than
CS-based hydrogels to achieve the same gelation temperature under the same
polymer's concentration. Additionally, the swelling, anti-bacteria, and
cytotoxicity experiments showed that PAEMCS-based hydrogels possessed excellent
hygroscopicity, high antibacterial activity against E. coli, S. aureus, or S.
epidermidis, and good cytocompatibility toward L929 cells or HUVECs,
respectively. All the results implied that PAEMCS-based hydrogels not only
maintained inherent multiple properties of chitosan but also possessed excellent
antibacterial activity, and might be promising antibacterial hydrogel dressings
used in wound therapy.
PMID- 28416399
TI - Fabrication of semisynthetic collagenic materials for mere/synergistic
adsorption: A model approach of determining dye allocation by systematic
characterization and optimization.
AB - Bovine collagen was functionalized by extensive process modifications for
fabricating tanned bovine collagen fibers (TBCFs), as a new semisynthetic macro-,
meso- and micro- porous adsorbent, of unprecedented physicochemical properties
and excellent industrial waste removal efficiency. Mere or interactive effects
were rationally understood, via analyzing monomer-dimer equilibrium, H-/J
aggregate formation, H-bonding, metachromasia, dye-dye complex formation etc.,
through extensive UV-vis analyses, during removal of acidic, like Acid Brown 369
(AB369), Acid Red 131 (AR131) and Acid Blue 113 (AB113) and basic, like Methylene
Blue (MB) dyes. A new strategy was introduced to determine the allocations of
these dyes, within macro-, meso- and micro-pores of TBCF, confirmed by FTIR, TGA,
DTG, DSC, XRD, SEM, EDX analyses, of both loaded and unloaded TBCFs, and by
measuring isotherm, kinetics, diffusion and thermodynamics parameters of
adsorption. Freundlich, Langmuir and Sips models were best fitted to AR131, AB113
and AB369, respectively. Interactive effects of concentration, temperature and
time, on adsorption capacities (ACs), were optimized via response surface
methodology (RSM). ACs of AR131, AB113 and AB369 were 38.29, 78.14 and 73.25mgg
1, respectively, at optimum conditions (i.e. adsorbent dose=0.25g, pHi=4,
concentration=200ppm and temperature=299K).
PMID- 28416400
TI - American Society for Metabolic and Bariatric Surgery: care pathway for
laparoscopic sleeve gastrectomy.
PMID- 28416401
TI - Polymeric nanoparticles for siRNA delivery: Production and applications.
AB - Gene therapy through the use of siRNA and a polymeric carrier are becoming an
efficient therapeutic option to conventional pharmaceutical formulations for the
treatment of deadly diseases, such as cancer, pulmonary, ocular and
neurodegenerative diseases. However, several considerations regarding the
stability, formulation, and efficacy have to be faced up until these systems
could be considered to be a marketable pharmaceutical products for to extend
siRNA application to clinical practice. This review is focused on the key
challenges of siRNA therapeutics, with special attention on the faced obstacles
and on the formulation-related difficulties, providing a list of requirements
needed for obtaining an ideal carrier for siRNA. Moreover, the current non-viral
polymers investigated for the realization of efficient carriers for siRNA are
described, with a special attention on synthetic polyamines such as
polyethylenimine (PEI), polysaccharides such as chitosan and inulin (INU), and
polyaminoacids such as alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA)
and poly-l-lysine (PLL).
PMID- 28416402
TI - Improvement of skin whitening agents efficiency through encapsulation: Current
state of knowledge.
AB - Hyperpigmentation is one of the most common skin disorder that affects both men
and women of all ethnic groups, caused by several factors, such as UV exposure
and skin inflammation. Topical whitening agents were found to be the best and the
least aggressive therapy for treating hyperpigmentation compared to instrumental
approaches. However, topical treatment faces several obstacles due to the low
stability of the whitening agents. Therefore, the encapsulation of these agents
was found to be crucial as it enhances their physicochemical stability and
increases their concentration at the targeted site via an improved skin
permeation, penetration or distribution. In this article, we review the
literature aimed to enhance the stability and the targeting of skin whitening
agents through their encapsulation in various nano and micro-particulate systems.
PMID- 28416403
TI - Feasibility of dsRNA treatment for post-clearing SPF shrimp stocks of newly
discovered viral infections using Laem Singh virus (LSNV) as a model.
AB - Using post-larvae derived from specific pathogen free (SPF) stocks in penaeid
shrimp farming has led to a dramatic increase in production. At the same time,
new pathogens of farmed shrimp are continually being discovered. Sometimes these
pathogens are carried by shrimp and other crustaceans as persistent infections
without gross signs of disease. Thus it is that a 5-generation stock of Penaeus
monodon SPF for several pathogens was found, post-stock-development, to be
persistently-infected with newly-discovered Laem Singh virus (LSNV). In this
situation, the stock developers were faced with destroying their existing stock
(developed over a long period at considerable cost) and starting the whole stock
development process anew in order to add LSNV to its SPF list. As an alternative,
it was hypothesized that injection of complementary dsRNA into viral-infected
broodstock prior to mating might inhibit replication of the target virus
sufficiently to reduce or eliminate its transmission to their offspring.
Subsequent selection of uninfected offspring would allow for post-clearing of
LSNV from the existing stock and for conversion of the stock to LSNV-free status.
Testing this hypothesis using the LSNV-infected stock described above, we found
that transmission was substantially reduced in several treated broodstock
compared to much higher transmission in buffer-injected broodstock. Based on
these results, the model is proposed for post-clearing of SPF stocks using dsRNA
treatment. The model may also be applicable to post-clearing of exceptional,
individual performers from grow-out ponds for return to a nucleus breeding
center.
PMID- 28416404
TI - Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the
United States including modified live virus vaccine (MLV) strains and field
strains from cattle.
AB - This study investigated the genetic and antigenic characterization of
parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time
PCR and viral genome sequencing, PI3V strains could be separated into PI3V types,
including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine
respiratory disease clinical signs and commercial vaccines in the U.S. with MLV
PI3V were typed using these molecular tests. All the MLV vaccine strains tested
were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines
were types heterologous to the vaccine type A. Also antigenic differences were
noted as PI3V C strains had lower antibody levels than PI3V A in serums from
cattle receiving MLV PI3V A vaccines. This study further demonstrates there is
genetic variability of U.S. PI3V strains and also antigenic variability. In
addition, isolates from cattle with BRD signs and receiving MLV vaccines may have
heterologous types to the vaccines, and molecular tests should be performed to
differentiate field from vaccine strains. Potentially the efficacy of current
PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.
PMID- 28416406
TI - Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and
Intravenous Tissue Plasminogen Activator.
AB - Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in
patients with nonvalvular atrial fibrillation. For patients who present with an
acute stroke despite dabigatran therapy, clinical data on the use of intravenous
tissue plasminogen activator (IV-tPA) is limited. There is an anticipated
increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in
patients on dabigatran therapy. In 2015, the humanized monoclonal antibody
fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant
effects of dabigatran. Dabigatran reversal with idarucizumab before
administration of IV-tPA might reduce the risk of sICH. We report a case of a 69
year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who
presented with an initial National Institutes of Health Stroke Scale (NIHSS) of
12. There was no early evidence of ischemic stroke or hemorrhage on head computed
tomography, and coagulation studies implied therapeutic dabigatran levels. After
controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA
was administrated beginning 197 minutes after he was last seen at his baseline.
Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the
left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient
was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated
that he was at his prestroke baseline, except for a complaint of worsened short
term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and
should be considered for acute stroke patients arriving in the IV-tPA time
window.
PMID- 28416405
TI - Development, Validation, and Assessment of an Ischemic Stroke or Transient
Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea.
AB - BACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used
routinely to guide clinicians regarding patient referral for polysomnography
(PSG), rely heavily on symptomatology. We sought to develop and validate a
cerebrovascular disease-specific OSA prediction model less reliant on
symptomatology, and to compare its performance with commonly used screening
instruments within a population with ischemic stroke or transient ischemic attack
(TIA). METHODS: Using data on demographic factors, anthropometric measurements,
medical history, stroke severity, sleep questionnaires, and PSG from 2
independently derived, multisite, randomized trials that enrolled patients with
stroke or TIA, we developed and validated a model to predict the presence of OSA
(i.e., Apnea-Hypopnea Index >=5 events per hour). Model performance was compared
with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the
Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age,
Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score.
RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck,
weight [in Pounds], Insulin resistance/diabetes, and National Institutes of
Health Stroke Scale) performed modestly better than other instruments in
identifying patients with OSA, showing reasonable discrimination in the
development (c-statistic .732) and validation (c-statistic .731) study
populations, and having the highest negative predictive value of all in
struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA
screening instruments when making decisions about referral for PSG. The high
negative predictive value of the SLEEP INventory may be useful in determining and
prioritizing patients with stroke or TIA least in need of overnight PSG.
PMID- 28416407
TI - Relationship between Hemorrhagic Complications and Target Vessels in Acute
Thrombectomy.
AB - PURPOSE: Intracranial hemorrhage after thrombectomy using a catheter to treat
acute major cerebral artery occlusion is known to exacerbate patient outcomes.
This study was performed to determine the relationship between middle cerebral
artery (MCA) tortuosity and postoperative hemorrhage. METHODS: We examined 111
consecutive patients who underwent acute thrombectomy for major intracranial
artery occlusion in the anterior circulation at our hospital between September
2013 and June 2016. Patients in whom intracranial hemorrhage or subarachnoid
hemorrhage was seen on head computed tomography 12-24 hours after surgery were
assigned to the hemorrhagic group, whereas all the other patients were assigned
to the nonhemorrhagic group. The groups were compared for tortuosity of the MCA,
which was evaluated by finding the top-to-bottom (TB) distance of the M1 segment
on anterior-posterior view angiograms. A modified Rankin scale score of 0-2 at 3
months after onset was considered a favorable prognosis. RESULTS: The hemorrhagic
group comprised 28 patients (25.2%) and the nonhemorrhagic group comprised 83
patients (74.8%). No significant difference in patient characteristics was seen
between the groups. The hemorrhagic group displayed significantly fewer patients
with a favorable prognosis (17.9% versus 43.4%, P = .016). The TB distance was
significantly greater in the hemorrhagic group (hemorrhagic group, 9.7 mm;
nonhemorrhagic group, 7.6 mm; P = .002); multivariate analysis also identified a
TB distance over 8.8 mm as a factor independently associated with postoperative
intracranial hemorrhage (P = .001). CONCLUSIONS: Post-thrombectomy hemorrhage was
significantly correlated with TB distance. A solution is needed for selecting and
combining devices used in patients with a TB distance over 8.8 mm.
PMID- 28416408
TI - [Description of an isoniazid-resistant tuberculosis outbreak in a block of
apartments].
PMID- 28416409
TI - [Recommendations for the unequivocal identification of the newborn].
AB - Newborn identification is a legal right recognised by international and national
laws. Moreover, improving the accuracy of correct patient identification is an
important goal of patient safety solutions programs. In this article, the
Standards Committee of the Spanish Society of Neonatology establishes
recommendations to ensure correct identification of the newborn whilst in
hospital. Currently, the most reliable method of identification of the newborn is
the combination of identification cord clamp and bracelets (mother bracelet,
newborn bracelet and cord clamp with the same number and identical and exclusive
barcode system for each newborn) and the collection of maternal and umbilical
cord blood samples (for DNA testing only for identification purposes).
PMID- 28416410
TI - Progressive Occlusion and Recanalization After Endovascular Treatment for 287
Unruptured Small Aneurysms (<5mm): A Single-Center 6-Year Experience.
AB - OBJECTIVE: We aimed to investigate the effect of coiling for small unruptured
intracranial aneurysms (UIAs) (<5 mm) on progressive occlusion and
recanalization, and the dubious factors related to progressive occlusion and
recanalization among UIAs without complete occlusion. METHODS: A total of 264
patients with 287 small UIAs were coiled in our institution between June 2009 and
December 2014. All UIAs were divided into small (3-5 mm) and very small (<3 mm)
groups, and UIAs without initial complete occlusion were divided into
progressive, stable, and recanalization groups. Baseline characteristics,
procedure-related complications, angiographic follow-up results, and clinical
outcomes were statistically analyzed. RESULTS: Among 287 aneurysms, 211 aneurysms
(73.5%) were completely coiled, 3 (1.2%) had intraoperative ruptures, and 12
(4.2%) had perioperative thromboembolic events. Angiographic follow-up was
available for 174 patients (65.9%), and the incidence of recanalization was 5.7%.
Among 56 aneurysms without complete occlusion, 43 (76.8%) had progressive
occlusion and 6 (10.7%) had recanalization. Anatomic results of initial and
follow-up between the small and very small groups were similar. On logistic
regression analysis, smaller size (<3 mm) without complete occlusion related to
recanalization (odds ratio, 8.0, 95% confidence interval 1.3-50.0; P = 0.026).
CONCLUSIONS: Our study suggested that coil embolization of small UIAs can achieve
a high rate of progressive occlusion and a low rate of recanalization during
follow-up. Anatomic results of initial and follow-up between small (3-5 mm) and
very small (<3 mm) groups were similar. Smaller size (<3 mm), without complete
occlusion, may relate to recanalization.
PMID- 28416411
TI - Awake High-Flow Extracranial to Intracranial Bypass for Complex Cerebral
Aneurysms: Institutional Clinical Trial Results.
AB - OBJECTIVE: Assess the potential added benefit to patient outcomes of "awake"
neurological testing when compared with standard neurophysiologic testing
performed under general endotracheal anesthesia. METHODS: Prospective study of 30
consecutive adult patients who underwent awake high flow extracranial to
intracranial (HFEC-IC) bypass. Clinical neurological and neurophysiologic
findings were recorded. Primary outcome measures were the incidence of
stroke/cerebrovascular accident (CVA), length of stay, discharge to
rehabilitation, 30-day modified Rankin scale score, and death. An analysis was
also performed of a retrospective control cohort (n = 110 patients who underwent
HFEC-IC for internal carotid artery (ICA) aneurysms under standard general
endotracheal anesthesia). RESULTS: Five patients (16.6%) developed clinical awake
neurological changes (4, contralateral hemiparesis; 1, ipsilateral visual
changes) during the 10-minute ICA occlusion test. These patients had 2 kinks in
the graft, 1 vasospasm, 1 requiring reconstruction of the distal anastomosis, and
1 developed blurring of vision that reversed after the removal of the distal
permanent clip on the ICA. Three of these 5 patients had asynchronous clinical
"awake" neurological and neurophysiologic changes. Two patients (7%) developed
CVA. Median length of stay was 4 days. Twenty-eight of 30 patients were
discharged to home. Median modified Rankin scale score was 1. There were no
deaths in this series. Absolute risk reduction in the awake craniotomy group (n =
30) relative to control retrospective group (n = 110) was 7% for CVA, 9% for
discharge to rehabilitation, and 10% for graft patency. CONCLUSIONS: Temporary
ICA occlusion during HFEC-IC bypass for ICA aneurysms in conjunction with awake
intraoperative clinical testing was effective in detecting a subset of patients
(n = 3, 10%) in whom neurological deficit was not detected by neurophysiologic
monitoring alone.
PMID- 28416412
TI - Successful Treatment of Symptomatic Intracranial Carotid Artery Stenosis Using a
24-mm Long Bare Metal Coronary Stent.
AB - BACKGROUND: Intracranial arterial atherosclerosis represents a common cause of
stroke. Despite aggressive and optimal medical management, many patients will
unfortunately suffer additional cerebrovascular events. The role of endovascular
intervention for intracranial atherosclerotic disease continues to be uncertain,
particularly in regard to extensive, symptomatic stenosis. CASE DESCRIPTION: We
present a case of a 42-year-old man with a complex medical history who presented
with recurrent ischemic stroke in the ipsilateral hemisphere despite optimal
medical management. Given the length of stenosis and the luminal size of the
intracranial cavernous and petrous segments of the internal carotid artery, we
used a bare metal coronary stent (4.0 mm * 24 mm). This represents one of the
longest stents deployed for intracranial disease reported in the literature.
CONCLUSIONS: This case illustrates that a long coronary stent might be
successfully used to manage extensive intracranial lesions. We also review the
efficacy of using 1 very long stent versus multiple overlapping stents, with
reference to the coronary angiography literature.
PMID- 28416413
TI - Evaluation of the PhysioTelTM Digital M11 cardiovascular telemetry implant in
socially housed cynomolgus monkeys up to 16weeks after surgery.
AB - INTRODUCTION: The novel PhysioTelTM Digital M11 telemetry implant was evaluated
in socially housed monkeys with respect to both safety pharmacological
cardiovascular (arterial blood pressure (BP), heart rate (HR) and
electrocardiogram (ECG)) and toxicological (clinical pathology and
histopathology) endpoints. METHODS: Telemetry and clinical pathology data were
obtained repeatedly up to 16weeks after surgery in four female cynomolgus
monkeys, followed by necropsy. Due to postsurgical complications, one spare
animal was included and only toxicological endpoints from the affected (fifth
animal) were reported. Continuous telemetry recordings were conducted at periods
without dosing and after ascending doses of moxifloxacin (0, 10, 30, 100mg/kg)
and L-NAME (0, 0.1, 1, 10mg/kg). Additionally, a retrospective power analysis was
conducted based on baseline M11 implant data from 32 other animals. RESULTS:
During periods without dosing, the cardiovascular endpoints were stable over time
and within normal ranges. Moxifloxacin and L-NAME elicited the expected
pharmacological responses with dose-dependent increase in QTca (8, 17, 22ms) and
BP (mean BP: 12, 21, 34mmHg), respectively. Expected intravascular and tissue
reactions were observed at the sites of the BP catheter and the transmitter.
Signs of infection (localised to the transmitter implantation site with
associated systemic effects) was noted in the fifth animal. No systemic
pathologies were seen in any animals. Power analysis (80% power) indicated that
the minimal differences which can be detected in a parallel group design (n=6)
are 7mmHg (mean BP), 16bpm (HR), 12ms (QTca). DISCUSSION: The M11 implant
provided stable, high quality ECG and BP data for a duration covering the length
of sub-chronic repeated dose toxicity studies without important impact on
toxicological endpoints. Adequate power in order to elucidate major treatment
related cardiovascular effects was demonstrated. However to avoid post-surgical
complications the implantation procedures should be carefully considered before
using the method.
PMID- 28416414
TI - Deep temporal models and active inference.
AB - How do we navigate a deeply structured world? Why are you reading this sentence
first - and did you actually look at the fifth word? This review offers some
answers by appealing to active inference based on deep temporal models. It builds
on previous formulations of active inference to simulate behavioural and
electrophysiological responses under hierarchical generative models of state
transitions. Inverting these models corresponds to sequential inference, such
that the state at any hierarchical level entails a sequence of transitions in the
level below. The deep temporal aspect of these models means that evidence is
accumulated over nested time scales, enabling inferences about narratives (i.e.,
temporal scenes). We illustrate this behaviour with Bayesian belief updating -
and neuronal process theories - to simulate the epistemic foraging seen in
reading. These simulations reproduce perisaccadic delay period activity and local
field potentials seen empirically. Finally, we exploit the deep structure of
these models to simulate responses to local (e.g., font type) and global (e.g.,
semantic) violations; reproducing mismatch negativity and P300 responses
respectively.
PMID- 28416415
TI - Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy
children.
AB - BACKGROUND: Fecal calprotectin may be used as a non-invasive method to assess the
effect of novel therapies on the gut in cystic fibrosis (CF). METHOD: Stools from
CF patients and healthy controls (HC) (0-10years old) were prospectively
collected for evaluation of temporal trends. RESULTS: 130 CF samples (64
subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal
calprotectin levels were different in CF patients and HC from 0 to 10years
(P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to
1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to
10years calprotectin was consistently higher in CF patients compared with HC
(P=0.007). CONCLUSIONS: Fecal calprotectin levels in children with CF and HC were
age-dependent and had distinct trajectories. Careful interpretation of
calprotectin is required if used in drug trials for CF, particularly in children
less than 4years old.
PMID- 28416416
TI - Flow Function of Pharmaceutical Powders Is Predominantly Governed by Cohesion,
Not by Friction Coefficients.
AB - The purpose of this study was to demonstrate that the flow function (FFc) of
pharmaceutical powders, as measured by rotational shear cell, is predominantly
governed by cohesion but not friction coefficients. Driven by an earlier report
showing an inverse correlation between FFc and the cohesion divided by the
corresponding pre-consolidation stress (Wang et al. 2016. Powder Tech. 294:105
112), we performed analysis on a large data set containing 1130 measurements from
a ring shear tester and identified a near-perfect inverse correlation between the
FFc and cohesion. Conversely, no correlation was found between FFc and friction
angles. We also conducted theoretical analysis and estimated such correlations
based on Mohr-Coulomb failure model. We discovered that the correlation between
FFc and cohesion can sustain as long as the angle of internal friction at
incipient flow is not significantly larger than the angle of internal friction at
steady-state flow, a condition covering almost all pharmaceutical powders. The
outcome of this study bears significance in pharmaceutical development. Because
the cohesion value is strongly influenced by the interparticle cohesive forces,
this study effectively shows that it is more efficient to improve the
pharmaceutical powder flow by lowering the interparticle cohesive forces than by
lowering the interparticle frictions.
PMID- 28416418
TI - Current Progress Toward a Better Understanding of Drug Disposition Within the
Lungs: Summary Proceedings of the First Workshop on Drug Transporters in the
Lungs.
AB - The School of Pharmacy and Pharmaceutical Sciences at Trinity College Dublin
hosted the "1st Workshop on Drug Transporters in the Lungs" in September 2016 to
discuss the impact of transporters on pulmonary drug disposition and their roles
as drug targets in lung disease. The workshop brought together about 30
scientists from academia and pharmaceutical industry from Europe and Japan and
addressed the primary questions: What do we know today, and what do we need to
know tomorrow about transporters in the lung? The 3 themes of the workshop were:
(1) techniques to study drug transporter expression and actions in the lungs; (2)
drug transporter effects on pulmonary pharmacokinetics-case studies; and (3)
transporters as drug targets in lung disease. Some of the conclusions of the
workshop were: suitable experimental models that allow studies of transporter
effects are available; data from these models convincingly show a contribution of
both uptake and efflux transporters on pulmonary drug disposition; the effects of
transporters on drug lung PK is now better conceptualized; some transporters are
associated with lung diseases. However, more work is needed to establish which of
the available models best translate to the clinical situation.
PMID- 28416417
TI - In Vitro Evaluation of Nasogastric Tube Delivery Performance of Esomeprazole
Magnesium Delayed-Release Capsules.
AB - Enteral feeding tubes are used to deliver food or drugs to patients who cannot
swallow. To deliver delayed-release drugs that are formulated as enteric coated
granules to these patients via feeding tubes requires that they be suspended in
water before administration. Importantly, the suspension of enteric granules in
water of varying pH can cause damage to the enteric coating and affect the
bioavailability of the drug. Here, analytical methods for testing acid resistance
stability and particle size distribution (PSD) of esomeprazole granules were used
to monitor the integrity of the granule enteric coating after water pretreatment
and delivery through an oral syringe and nasogastric (NG) tube. Granules from
esomeprazole magnesium delayed-release capsules were transferred to an oral
syringe, suspended in water, and delivered on the bench through an NG tube.
Subsequently, acid resistance stability (i.e., the amount of drug released after
2-h acid dissolution) was determined via high-performance liquid chromatography,
and the PSD were measured with a laser diffraction system. All the granules
demonstrated acid resistance stability when the granules were delivered
immediately (0 min incubation) through the oral syringe and NG tube. In contrast,
some granules demonstrated significant drug release during acid exposure after a
15-min incubation period which mimics a possible delay in delivery of the drug
from the syringe by the caregiver. A bimodal PSD was observed with these
granules, which was attributed to debris from damaged enteric coating and
particle agglomeration. The methods developed in this study could be used to
distinguish batches with suboptimal product quality for delivery using NG tubes
and to confirm the substitutability of generic drug products for this alternative
route of administration.
PMID- 28416419
TI - Evaluation of Renal Transporter Inhibition Using Creatinine as a Substrate In
Vitro to Assess the Clinical Risk of Elevated Serum Creatinine.
AB - Creatinine is a widely accepted biomarker for renal toxicity, but its renal
clearance via transporter-mediated active secretion is significant. For a given
new chemical entity, therefore, elevations in serum creatinine (SCr) can be
caused by the inhibition of renal transporter(s) without renal toxicity. In the
present study, an effort was made to assess the correlation between the
inhibition of renal transporters in vitro and elevations in SCr. A total of 15
compounds were chosen based on their known effect on SCr and minimal impact on
glomerular filtration rate. Their inhibition potencies against the major
creatinine renal transporters, including organic cation transporter 2, organic
anion transporter 2, and 2 forms of multidrug and toxin extrusion (MATE1 and
MATE2K), were assessed in transporter-transfected cell lines using creatinine as
a probe substrate. Collectively, the data suggest that the observed elevations in
SCr can be attributed to the inhibition of renal transporter(s), but inhibition
of renal transporters does not necessarily lead to elevated SCr. Thus, renal
transporter inhibition data can be used to rationalize SCr changes. Additionally,
differing renal transporter inhibition potencies using creatinine and metformin
as probe substrates suggest that substrate-dependent inhibition exists for some
compounds.
PMID- 28416421
TI - [Endoscopy is not so two-dimensional and microsurgery not so three-dimensional].
PMID- 28416420
TI - Identification of Endogenous Biomarkers to Predict the Propensity of Drug
Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.
AB - Drug transporters expressed in liver and kidney play a critical role in the
elimination of a wide range of drugs and xenobiotics and inhibition of these
transporters may therefore cause clinically significant drug-drug interactions
(DDIs). Currently, in vitro transporter inhibition data are used to assess the
risk that a drug candidate may act as an inhibitor of a transporter in patients
at clinically relevant exposures. However, this approach is hampered by low
confidence in in vitro to in vivo extrapolations, and large inter-system and
inter-laboratory variability in in vitro data. Several endogenous compounds have
been identified as substrates of drug transporters. Determining the impact of
perpetrator drugs on the plasma or urinary exposure of these potential endogenous
biomarkers in humans is being explored as an alternative approach to assess the
DDI liability of drug candidates, especially in early drug development. In this
review, we provide an overview of recently identified biomarkers used to study
the inhibition of hepatic and renal transporters; summarize the methods and
strategies employed to identify biomarkers; and discuss the utility, limitation,
and future direction of biomarker approaches to predict transporter-mediated
DDIs.
PMID- 28416422
TI - [Penetrating air gun pellet into the orbital apex].
AB - A foreign body penetrating into the intraconal orbital compartment poses a
surgical challenge because of its deep location behind the globe and near the
optic nerve. We present a case of an air gun pellet lodged into the orbital apex,
which was removed via superolateral orbitotomy through coronal incision. This
additional craniofacial technique is a safe procedure to access the lateral
aspect of the intraconal compartment in the unusual event of having to remove an
orbital foreign body.
PMID- 28416423
TI - Dietary administration of sodium alginate ameliorated stress and promoted immune
resistance of grouper Epinephelus coioides under cold stress.
AB - Grouper, Epinephelus coioides, fed a diet containing sodium alginate at 0
(control, named C) and 1.0 g kg-1 (named S) at a temperature of 28 degrees C for
12 days, were then further individually transferred to 28 (two groups named C-28
and S-28) or 20 degrees C (two groups named C-20 and S-20), and immune
parameters and stress indexes were measured at the beginning and after 6, 12, 24
and 48 h of exposure. Examination of immune parameters revealed that the
alternative complement activity (ACH50), lysozyme activity, phagocytic activity,
superoxide dismutase, and respiratory bursts significantly increased in groupers
fed the sodium alginate-containing diet for 12 days, and were higher in the S-28
than those of the C-28 and S-20 groups, which were higher than those of the C-20
group from 6 to 48 h except for ACH50 at 48 h, respiratory bursts at 48 h, and
lysozymes at 6 h. For the assessment of stress indicators, cortisol, glucose, and
lactate levels of serum significantly decreased in grouper fed the sodium
alginate-containing diet for 12 days, and were higher in the C-20 group than
those of the C-28 and S-20 groups, which were higher than those of the S-20 group
at 6-48 h. In another experiment, grouper fed the test diet for 12 days at a
temperature of 28 degrees C were challenged with Photobacterium damselae subsp.
piscicida at a dose of 5 * 103 colony-forming units (cfu) (g fish)-1, and then
individually transferred to 28 or 20 degrees C. The survival rate of challenged
fish of the C-28 group was significantly lower than those of challenged fish of
the C-20 and S-28 groups, which were significantly lower than that of challenged
fish of the S-20 group. All challenged fish of the S-20 group survived. Survival
rates over 144 h were 30.0%, 70.0%, and 56.7% for the C-28, C-20, and S-28
groups, respectively. Our results indicated that dietary sodium alginate
administration downregulated stress response indicators, enhanced immune
responses, and prevented impacts of physiologic stress responses,
immunosuppression, and susceptibility to P. damselae subsp. piscicida in grouper
subjected to cold stress. Grouper cultured at 28 degrees C were more susceptible
to P. damselae subsp. piscicida infection.
PMID- 28416424
TI - [First requests for a regional pediatric palliative care team: A prospective and
observational study].
AB - INTRODUCTION: In France, 26 regional pediatric palliative care teams (ERRSPP)
were created between 2008 and 2012. We conducted the first prospective French
study to describe the main specifications of the initial contact with an ERRSPP
and to analyze the responses given. DESIGN AND METHODS: All the requests for
interventions on the part of the ERRSPP were collected between September 2013 and
September 2014. We prospectively completed a questionnaire on the patient's
clinical and demographic data (age, sex, disease), details regarding the request
(type of applicant, unit's specialty, request pattern), and the answers provided
(interval between diagnosis and request, duration of care by ERRSPP, death,
changes compared to the initial request). The diseases were classified within one
of the six groups of palliative pediatric care diseases, based on the standards
of the Canadian palliative care association. RESULTS: We gathered 67 requests, 61
relating to patients. The median age at the request was 49.8 months (range: 2.3
145). The original pattern was multiple: multidisciplinary decision-making (42
%), coordination of care (34 %), symptom management (21 %), logistic support for
home care (19 %), education (9 %) and case discussion (6 %). Requests concerning
multidisciplinary decision-making were predominant within the neonatal period (61
%); coordination of care was significant for children and adolescents (78 % after
4 years of age). The study of the median time from diagnosis to request compared
to the groups of diseases revealed a short time in group 5 (neonatology: 0.36
months) and a long time in group 4 (irreversible and nonscalable diseases: 54.6
months) (P<0.001). At the end of the study, the follow-up of 50.8 % of the
patients by ERRSPP was still going on (median duration of care by the ERRSPP of
Languedoc-Roussillon region [ERRSPP-LR], 3.4 months [range: 0.2-5.5]). No request
was formulated by a general practitioner. CONCLUSION: This study shows the
heterogeneity of the initial contact made with an ERRSPP, confirming its
different assignments and the need for a multidisciplinary team. The ERRSPP's
answer was expanded in half of the cases, attesting to the changing needs over
time.
PMID- 28416425
TI - [Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3
year-old boy].
AB - Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We
describe a case of bilateral simultaneous facial nerve palsy associated with
Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to
the diagnosis of EBV infection: the clinical situation (fever, stomachache, and
throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count),
seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a
positive blood EBV polymerase chain reaction (9.3*103 copies of EBV-DNA). An MRI
brain scan showed bilateral gadolinium enhancement of the facial nerve. A
treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was
implemented. Antibiotics were stopped after the diagnosis of Lyme disease was
ruled out. The patient's facial weakness improved within a few weeks. Bilateral
facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic
in only 20% of cases. Therefore, it requires further investigation and
examination to search for the underlying etiology. Lyme disease is the first
infectious disease that should be considered in children, especially in endemic
areas. An antibiotic treatment effective against Borrelia burgdorferi should be
set up until the diagnosis is negated or confirmed. Further examination should
include a blood test (such as immunologic testing, and serologic testing for
viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and
an MRI brain scan to exclude any serious or curable underlying etiology. Facial
bilateral nerve palsy associated with EBV is rarely described in children.
Neurological complications have been reported in 7% of all EBV infections. The
facial nerve is the most frequently affected of all cranial nerves. Facial palsy
described in EBV infections is bilateral in 35% of all cases. The physiopathology
is currently unknown. Prognosis is good most of the time.
PMID- 28416426
TI - [The Jarde law, a real simplification of research in France?]
AB - The Jarde law was voted in 2012 and its implementing decrees were published in
November 2016. The delay between the vote and the decrees highlights the
difficulties encountered. This law concerns all research, interventional and
otherwise, involving the human person. Each research study must receive the
approval of a randomly assigned ethics committee or Committee for the Protection
of Persons. The approach here is based on risk in three types of study:
interventional studies, studies with minimal risk and intervention, and non
interventional studies (observational studies). The main changes are: simplified
informed consent for pediatric studies and possible enrolment for people not
affiliated with a social health care system in non-interventional research. The
law provides clarification for changes in the purpose of biological collections.
For vigilance, the notions of "new facts" and "urgent security measures" have
emerged. Although this law appears to be an advancement, some concerns still need
to be clarified. The main problem arises from the foreseeable extension of the
delay to implement research. Medical research is a competition where time is
valuable. Colleagues working on cosmetics research have already anticipated these
difficulties. On February 8, 2017, the decrees of the Jarde law were suspended
for cosmetics studies. Will the Jarde law be suspended for all French clinical
research?
PMID- 28416427
TI - [Femoral Nora lesion in a 5-year-old child].
PMID- 28416429
TI - [Life-threatening sleepwalking (Elpenor's syndrome) in a 10-year-old child].
AB - : Though benign in the majority of cases, sleepwalking sometimes causes injuries
due, among other causes, to falls. Such accidents can be life-threatening - a
situation that has been termed Elpenor syndrome (in reference to an accident
experienced by a character in Homer's epic The Odyssey) - in particular when
entailing defenestration. This syndrome has been described in adults and
adolescents; we report here a case in a child. OBSERVATION: This 10-year-old girl
was admitted at night to our hospital after a 3-m fall at home. She was alert
(Glasgow score, 15) at admission; a frontal wound and a deformation of the right
wrist were noted. Brain CT scans showed a frontal skull fracture and frontal lobe
contusion, wrist x-rays showed a displaced right fracture. The patient underwent
urgent neurosurgery (wound excision and suture after reduction of skull fracture)
and closed reduction and immobilization of the wrist fracture, both under general
anesthesia. She underwent a psychiatric assessment in the intensive care unit 3
days after her fall. She was alert, well-oriented in time and space, and spoke
fluently. She had no memory of her fall, only remembering going to bed in the
evening before the accident and waking up in the ambulance on the way to the
hospital. She displayed no sign of a concurrent mental illness and no suicidal
ideas. Her parents reported that the evening of the accident she and her two
brothers had all fallen asleep about 11:00 pm while watching TV, in the double
bed of the guest room, placed just beside its window. At approximately 1:00 am,
her father, who was going to bed and had just made noise in the hall, heard a cry
from the guest room. He entered the room immediately and saw the opened window
and his daughter lying on the outside ground; the brothers only awakened after
the fall. The family had returned 2 days before from a 6-month stay in the United
States, with jet-lag, sleep deprivation, and a disorganized sleep/wake rhythm in
the patient. There was no medication before the accident, no substance use
(including caffeine), and no concurrent medical problem. Over the 2 preceding
years, the patient had undergone two witnessed episodes of early-nighttime
arousal with altered consciousness and calm wandering (including going downstairs
on one occasion), both strongly suggesting sleepwalking. There was a history of
sleepwalking in her father and her older brother. Life-threatening sleepwalking
(Elpenor syndrome) was diagnosed. The child and her parents were educated about
sleepwalking; regularization of sleep schedules and sleep extension (avoidance of
sleep deprivation, short napping when possible) were prescribed. We also
recommended securing the home (bed, windows, and stairways). No pharmacological
treatment was instituted. During the following 18 months, the child manifested
only one noted sleepwalking episode, without risk-taking. She had no neurological
or psychopathological sequela from her accident, of which she never had a memory.
CONCLUSION: Elpenor syndrome can occur in a child; consequently, it is important
to inform parents of children with sleepwalking about the necessity of always
securing the night-time environment.
PMID- 28416428
TI - [Nasogastric rehydration for treating children with gastroenteritis].
AB - INTRODUCTION: When oral rehydration is not feasible, enteral rehydration via the
nasogastric route has been the ESPGHAN recommended method of rehydration since
2008, rather than intravenous rehydration (IVR), for children with acute
gastroenteritis. However, these recommendations are rarely followed in France.
Since 2011, in case of failure of oral rehydration, enteral rehydration has been
used as a first-line therapy in the Children's Emergency Department at the
Grenoble-Alpes University Hospital. PURPOSE: The aims of the study were to
compare the length of the hospital stay, the duration of initial rehydration, and
the incidence of complications and failure with the use of enteral nasogastric
versus intravenous rehydration. METHODS: This study compared two cohorts of
children (<3 years of age) with mild-to-moderate dehydration caused by acute
gastroenteritis and failure of rehydration via the oral route. The first group
(winter 2010-2011) was managed according to the previous protocol (intravenous
rehydration). The second group (winter 2011-2012) was managed according the new
protocol (nasogastric tube rehydration [NGR]). The rest of the gastroenteritis
management was identical in both groups. RESULTS: A total of 132 children were
included, 65 were treated with nasogastric tube rehydration (NGR) and 67 with
intravenous rehydration. There was a significant reduction in the duration of
hospitalization in the post-emergency unit in the NGR group: 23.6h vs 40.1h
(P<0.05). The duration of initial rehydration was also significantly reduced
(10.5h vs 22.0h). There was no significant difference regarding serious adverse
events. However, the NGR group presented more mild adverse events (22 vs 7,
P<0.05) and more treatment failures (15.3% vs 3%, P=0.013). CONCLUSION:
Nasogastric rehydration reduces the duration of rehydration and the length of the
hospital stay without increasing the incidence of serious adverse events for
dehydrated children hospitalized for acute gastroenteritis.
PMID- 28416430
TI - [Extracorporeal membrane oxygenation in critically ill neonates and children].
AB - Extracorporeal membrane oxygenation is used as a last resort during neonatal and
pediatric resuscitation in case of refractory circulatory or respiratory failure
under maximum conventional therapies. Different types of ECMO can be used
depending on the initial failure. The main indications for ECMO are refractory
respiratory failure (acute respiratory distress syndrome, status asthmaticus,
severe pneumonia, meconium aspiration syndrome, pulmonary hypertension) and
refractory circulatory failure (cardiogenic shock, septic shock, refractory
cardiac arrest). The main contraindications are a gestational age under 34 weeks
or birth weight under 2kg, severe underlying pulmonary disease, severe immune
deficiency, a neurodegenerative disease and hereditary disease of hemostasis.
Neurological impairment can occur during ECMO (cranial hemorrhage, seizure or
stroke). Nosocomial infections and acute kidney injury are also frequent
complications of ECMO. The overall survival rate of ECMO is about 60 %. This
survival rate can change depending on the initial disease: from 80 % for meconium
aspiration syndrome to less than 10 % for out-of-hospital refractory cardiac
arrest. Recently, mobile ECMO units have been created. These units are able to
perform ECMO out of a referral center for untransportable critically ill
patients.
PMID- 28416431
TI - [Atypical osteochondroma in a 5-year-old child].
PMID- 28416432
TI - [Transverse reductional anomaly and atypical fibrodysplasia ossificans
progressiva: A case diagnosed late].
AB - Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by
the association of congenital bone abnormalities and extraskeletal ossification
flare-ups occurring in muscles and fasciae. Early diagnosis is important to
prevent ossification flare-ups, but some atypical presentations can lead to
errors in diagnosis and therefore delay. Here, we report on a case of an atypical
presentation of FOP in a girl, in whom prominent transverse reductional
abnormalities delayed diagnosis. The patient developed extraskeletal
ossifications and progressive fibrosis that led to motor restrictions. Since
early diagnosis is important, we discuss the clinical presentations of FOP and
the differential diagnoses.
PMID- 28416433
TI - Addressing the Hidden Burden of Malnutrition for Hospitalized Patients.
PMID- 28416434
TI - Malnutrition Diagnosis during Adult Inpatient Hospitalizations: Analysis of a
Multi-Institutional Collaborative Database of Academic Medical Centers.
AB - BACKGROUND: Malnutrition is a significant problem for hospitalized patients.
However, the true prevalence of reported malnutrition diagnosis in real-world
clinical practice is largely unknown. Using a large collaborative multi
institutional database, the rate of malnutrition diagnosis was assessed and used
to assess institutional variables associated with higher rates of malnutrition
diagnosis. OBJECTIVE: The aim of this study was to define the prevalence of
malnutrition diagnosis reported among inpatient hospitalizations. DESIGN: The
University Health System Consortium (Vizient) database was retrospectively
reviewed for reported rates of malnutrition diagnosis. PARTICIPANTS/SETTING: All
adult inpatient hospitalization at 105 member institutions during fiscal years
2014 and 2015 were evaluated. MAIN OUTCOME MEASURES: Malnutrition diagnosis based
on the presence of an International Classification of Diseases-Ninth Revision
diagnosis code. STATISTICAL ANALYSIS: Hospital volume and publicly available
hospital rankings and patient satisfaction scores were obtained. Multiple
regression analysis was performed to assess the association between these
variables and reported rates of malnutrition. RESULTS: A total of 5,896,792
hospitalizations were identified from 105 institutions during the 2-year period.
It was found that 292,754 patients (5.0%) had a malnutrition diagnosis during
their hospital stay. By institution, median rate of malnutrition diagnosis during
hospitalization was 4.0%, whereas the rate of severe malnutrition diagnosis was
0.9%. There was a statistically significant increase in malnutrition diagnosis
from 4.0% to 4.9% between 2014 and 2015 (P<0.01). Institutional factors
associated with increased diagnosis of malnutrition were higher hospital volume,
hospital ranking, and patient satisfaction scores (P<0.01). CONCLUSIONS: Missing
a malnutrition diagnosis appears to be a universal issue because the rate of
malnutrition diagnosis was consistently low across academic medical centers.
Institutional variables were associated with the prevalence of malnutrition
diagnosis, which suggests that institutional culture influences malnutrition
diagnosis. Quality improvement efforts aimed at improved structure and process
appear to be needed to improve the identification of malnutrition.
PMID- 28416435
TI - Omics and cytokine discovery in fish: Presenting the Yellowtail kingfish (Seriola
lalandi) as a case study.
AB - A continued programme of research is essential to overcome production bottlenecks
in any aquacultured fish species. Since the introduction of genetic and molecular
techniques, the quality of immune research undertaken in fish has greatly
improved. Thousands of species specific cytokine genes have been discovered,
which can be used to conduct more sensitive studies to understand how fish
physiology is affected by aquaculture environments or disease. Newly available
transcriptomic technologies, make it increasingly easier to study the
immunogenetics of farmed species for which little data exists. This paper reviews
how the application of transcriptomic procedures such as RNA Sequencing (RNA-Seq)
can advance fish research. As a case study, we present some preliminary findings
using RNA-Seq to identify cytokine related genes in Seriola lalandi. These will
allow in-depth investigations to understand the immune responses of these fish in
response to environmental change or disease and help in the development of
therapeutic approaches.
PMID- 28416436
TI - Molecular cloning of chicken interleukin-17B, which induces proinflammatory
cytokines through activation of the NF-kappaB signaling pathway.
AB - Interleukin (IL)-17B is a little known member of the IL-17 cytokine family, which
plays an important role in immunity by regulating the expression of
proinflammatory cytokines. In this study, we determined the coding sequence and
biological functions of a novel chicken IL-17B (chIL-17B). The full-length chIL
17B coding sequence includes 567 nucleotides encoding 188 amino acids, which was
identified in small intestinal epithelial cells. The chIL-17B protein shares
96.48% amino acid sequence identity with turkey, 92.57% with duck, and 44.92
64.06% with mammalian IL-17B proteins. ChIL-17B shares three exons and two
introns with mammals, turkey, and duck. Moreover, IL-17B mRNA was more highly
expressed than IL-17A mRNA in several organs of chickens infected with Salmonella
and was upregulated in chicken cell lines following LPS stimulation. In addition,
in chicken cell lines, chIL-17B induced the mRNA expression of several
proinflammatory cytokines, including IL-1beta, IL-6, LITAF, and INF-gamma, but
not IL-17A, and activated MyD88, TAK1, NF-kappaB1, and SOCS1, which are
associated with the NF-kappaB signaling pathway. Taken together, chicken
interleukin-17B plays a critical role in host defense against the bacterial
pathogens, and regulates proinflammatory cytokines by activating the NF-kappaB
signaling pathway.
PMID- 28416437
TI - The computed tomography-based fractal analysis of trabecular bone structure may
help in detecting decreased quality of bone before urgent spinal procedures.
AB - BACKGROUND CONTEXT: To date, no reliable method is available to determine the
parameters of bone density based on the routine spinal computed tomography (CT)
in the emergency setup. We propose the use of fractal analysis to detect patients
with poor quality of bone before urgent or semi-urgent spinal procedures.
PURPOSE: This study aimed to validate the hypothesis that the CT-based fractal
analysis of the trabecular bone structure may help in detecting patients with
poor quality of bone before urgent spinal procedures. STUDY DESIGN: This is a
retrospective analysis of prospectively collected data. METHODS: Patients in whom
the dual-energy x-ray absorptiometry (DEXA) scan and lumbar spine CT were
performed at an interval of no more than 3 months were randomly selected from a
prospectively collected database. Diagnostic axial CT scans of L2, L3, and L4
vertebrae were processed to determine the fractal dimension (FD) of the
trabecular structure of each spinal level. Box-count method and ImageJ 1.49
software were used. The FD was compared with the results of the DEXA scan: bone
mineral density (BMD) and T-score by mean of correlation coefficients. Receiver
operating characteristic curve analysis was later performed to determine the
cutoff value of FD. RESULTS: A total of 102 vertebral levels obtained from 35
patients (mean age 60+/-18 years; 29 female) were analyzed. The FD was
significantly higher in the group of patients with decreased bone density (DBD)
(T-score<-1.0) (1.67 vs. 1.43; p<.0001) and negatively correlated with BMD (R
Spearman, -0.53; p<.0001) and T-score (-0.49; p<.0001). Receiver operating
characteristic curve analysis revealed that a cutoff value of FD>1.53 indicates
DBD (p<.0001; area under the ROC curve [AUC], 0.84; 95% confidence interval [CI],
0.76-0.91). CONCLUSIONS: This study shows that fractal analysis of the lumbar
spine CT images may be used to determine bone density before spinal
instrumentation (eg, metastatic or traumatic cord compression). Further
prospective studies comparing results of the fractal analysis of CT scans with
quantitative CT (qCT) are warranted.
PMID- 28416439
TI - Clinical and radiographic outcomes of bilateral decompression via a unilateral
approach with transforaminal lumbar interbody fusion for degenerative lumbar
spondylolisthesis with stenosis.
AB - BACKGROUND CONTEXT: Laminectomy with posterior lumbar interbody fusion (PLIF) has
been shown to achieve satisfactory clinical outcomes, but it leads to potential
adverse consequences associated with extensive disruption of posterior bony and
soft tissue structures. PURPOSE: This study aimed to compare the clinical and
radiographic outcomes of bilateral decompression via a unilateral approach (BDUA)
with transforaminal lumbar interbody fusion (TLIF) and laminectomy with PLIF in
the treatment of degenerative lumbar spondylolisthesis (DLS) with stenosis. STUDY
DESIGN: This is a prospective cohort study. PATIENT SAMPLE: This study compared
43 patients undergoing BDUA+TLIF and 40 patients undergoing laminectomy+PLIF.
OUTCOME MEASURES: Visual analog scale (VAS) for low back pain and leg pain,
Oswestry Disability Index (ODI), and Zurich Claudication Questionnaire (ZCQ)
score. METHODS: The clinical outcomes were assessed, and intraoperative data and
complications were collected. Radiographic outcomes included slippage of the
vertebra, disc space height, segmental lordosis, and final fusion rate. This
study was supported by a grant from The National Natural Science Foundation of
China (81572168). RESULTS: There were significant improvements in clinical and
radiographic outcomes from before surgery to 3 months and 2 years after surgery
within each group. Analysis of leg pain VAS and ZCQ scores showed no significant
differences in improvement between groups at either follow-up. The mean
improvements in low back pain VAS and ODI scores were significantly greater in
the BDUA+TLIF group than in the laminectomy+PLIF group. No significant difference
was found in the final fusion rate at 2-year follow-up. The BDUA+TLIF group had
significantly less blood loss, shorter length of postoperative hospital stay, and
lower complication rate compared with the laminectomy+PLIF group. CONCLUSIONS:
When compared with the conventional laminectomy+PLIF procedure, the BDUA+TLIF
procedure achieves similar and satisfactory effects of decompression and fusion
for DLS with stenosis. The BDUA+TLIF procedure appears to be associated with less
postoperative low back discomfort and quicker recovery.
PMID- 28416438
TI - NSAID use in intervertebral disc degeneration: what are the effects on matrix
homeostasis in vivo?
AB - BACKGROUND CONTEXT: Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely
used treatment for low back pain (LBP). Literature on NSAID use in articular
cartilage has shown detrimental effects; however, minimal data exist to detail
the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a
major cause of LBP, we explored the effects of indomethacin, a commonly used
NSAID, on disc matrix homeostasis in an animal model of IDD. PURPOSE: This study
aimed to determine the effects of oral indomethacin administration on IDD in an
in vivo rabbit model. This study hypothesized that indomethacin use would
accelerate the progression of IDD based upon serial imaging and tissue outcomes.
STUDY DESIGN/SETTING: This was a laboratory-based, controlled, in vivo evaluation
of the effects of oral indomethacin administration on rabbit intervertebral
discs. METHODS: Six skeletally mature New Zealand white rabbits were divided into
two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture
plus indomethacin (Punc+Ind group). The Punc+Ind group received daily
administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging
(MRI) was obtained at 0, 4, 8, and 12 weeks. The MRI index and the nucleus
pulposus (NP) area were calculated. Discs were harvested at 12 weeks for
determination of disc glycosaminoglycan (GAG) content, relative gene expression
measured by real-time polymerase chain reaction, and histologic analyses.
RESULTS: The MRI index and the NP area of punctured discs in the Punc+Ind group
demonstrated no worsening of degeneration compared with the Puncture group.
Histologic analysis was consistent with less severe disc degeneration in the
Punc+Ind group. Minimal differences in gene expression of matrix genes were
observed between Puncture and Punc+Ind groups. The GAG content was higher in
animals receiving indomethacin in both annulus fibrosus and NP at adjacent
uninjured discs. CONCLUSIONS: Oral indomethacin administration did not result in
acceleration of IDD in an in vivo rabbit model. Future research is needed to
ascertain long-term effects of indomethacin and other NSAIDs on disc matrix
homeostasis.
PMID- 28416440
TI - Inhibition of the PI3K-Akt-mTOR signaling pathway in T lymphocytes in patients
with active tuberculosis.
AB - OBJECTIVES: To investigate PI3K-Akt-mTOR signaling pathway changes and the
proliferation of FoxP3+Treg cells in patients with active tuberculosis. METHODS:
We isolated PBMCs and CD4+CD25+FoxP3+Treg cells from peripheral blood collected
from patients with active tuberculosis and healthy controls. We compared the
proportion and MFI of PI3K-Akt-mTOR pathway components and PTEN by flow cytometry
using specific cell-surface and intracellular markers. Moreover, we detected the
specific secretory proteins ESAT-6 and Ag85B, cytokines IL-10, TGF-beta1 and IL
35 in serum by ELISA. RESULTS: Compared with healthy controls, the proportions of
CD3+Akt+, CD3+p-Akt+, CD3+mTOR+, CD3+p-mTOR+ and CD3+PTEN+ cells, in the T
lymphocyte population of patients with active tuberculosis, were decreased
(p<0.05), while CD3+FoxP3+ cells were increased (p=0.013). Similarly, for
CD4+CD25+FoxP3+Treg cells, the proportions of Akt+ cells, p-Akt+ cells, mTOR+
cells, p-mTOR+ cells and PTEN+ cells were decreased (p<0.05) in patients with
active tuberculosis. Compared with healthy controls, the levels of ESAT-6 and
Ag85B were higher in patients with active tuberculosis (p<0.001). Levels of IL-10
and TGF-beta1 were higher (p<0.001), whereas the level of IL-35 was lower
(p<0.001). CONCLUSION: The PI3K-Akt-mTOR signaling pathway in T lymphocytes and
CD4+CD25+FoxP3+Treg cells was inhibited, which could explain why M.tuberculosis
can induce FoxP3+Treg cell to expand.
PMID- 28416442
TI - Allopregnanolone decreases interictal spiking and fast ripples in an animal model
of mesial temporal lobe epilepsy.
AB - The objective of this study was to characterize the impact of allopregnanolone, a
neurosteroid that acts as a positive allosteric modulator of synaptic and
extrasynaptic GABAA receptors, on interictal spikes and high-frequency
oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine
model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats
experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment
with allopregnanolone (9.6-12.8 mg/kg/day) on the following day. On day 4 after
SE, video-depth EEG recordings from the hippocampal CA3 subfield and the
entorhinal cortex were initiated and continued for 12 consecutive days. We found
that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6%
(2/7) of allopregnanolone-treated animals. Interictal spikes occurred less
frequently in the CA3 subfield of allopregnanolone-treated rats (n = 4) than in
untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous
seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to
both untreated groups (p < 0.05). Finally, allopregnanolone-treated rats had
significantly lower rates of interictal spikes with fast ripples (250-500 Hz)
compared to untreated animals but only in CA3 (p < 0.05). Our findings show that
allopregnanolone reduces the frequency of interictal spikes and fast ripples in
CA3, a structure that plays an important role in ictogenesis and epileptogenesis.
Neurosteroids may therefore influence pathological network activity leading to
spontaneous seizures following pilocarpine-induced SE. Recordings after
termination of allopregnanolone treatment will be however required to establish
whether allopregnanolone exerts disease-modifying properties.
PMID- 28416441
TI - Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct
ligated rat model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Glechoma
hederacea is frequently prescribed to patients with cholelithiasis, dropsy,
abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main
bioactive components of Glechoma hederacea. AIM OF THE STUDY: This study was
aimed to investigate the hepatoprotective potential of hot water extract of
Glechoma hederacea against cholestatic liver injury in rats. MATERIALS AND
METHODS: Cholestatic liver injury was produced by ligating common bile ducts in
Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were
orally administrated using gastric gavages. Liver tissues and bloods were
collected and subjected to evaluation using histological, molecular, and
biochemical approaches. RESULTS: Using a rat model of cholestasis caused by bile
duct ligation (BDL), daily oral administration of Glechoma hederacea hot water
extracts showed protective effects against cholestatic liver injury, as evidenced
by the improvement of serum biochemicals, ductular reaction, oxidative stress,
inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced
transforming growth factor beta-1 (TGF-beta1), connective tissue growth factor,
and collagen expression, and the anti-fibrotic effects were accompanied by
reductions in alpha-smooth muscle actin-positive matrix-producing cells and
Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory
cell infiltration/accumulation, NF-kappaB and AP-1 activation, and inflammatory
cytokine production. Further studies demonstrated an inhibitory effect of
Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll
like receptor-4 (TLR4) intracellular signaling pathways. CONCLUSIONS: The
hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of
Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of
daily Glechoma hederacea extracts supplementation were associated with anti
oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down
regulation of NF-kappaB, AP-1, and TGF-beta/Smad signaling, probably via
interference with the HMGB1/TLR4 axis.
PMID- 28416444
TI - The pharmacology of voltage-gated sodium channel activators.
AB - Toxins and venom components that target voltage-gated sodium (NaV) channels have
evolved numerous times due to the importance of this class of ion channels in the
normal physiological function of peripheral and central neurons as well as
cardiac and skeletal muscle. NaV channel activators in particular have been
isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea
anemone and are also produced by plants, bacteria and algae. These compounds have
provided key insight into the molecular structure, function and
pathophysiological roles of NaV channels and are important tools due to their at
times exquisite subtype-selectivity. We review the pharmacology of NaV channel
activators with particular emphasis on mammalian isoforms and discuss putative
applications for these compounds. This article is part of the Special Issue
entitled 'Venom-derived Peptides as Pharmacological Tools.'
PMID- 28416443
TI - Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.
AB - Astrocytes possess many of the same signalling molecules as neurons. However, the
role of astrocytes in information processing, if any, is unknown. Using
electrophysiological and imaging methods, we report the first evidence that
astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found
that mGlu2 receptor activity reduces inhibitory transmission from the thalamic
reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC
frequencies in VB slices were reduced by the Group II mGlu receptor agonist
LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM)
LY487379 co-application (30 nM LY354740: 10.0 +/- 1.6% reduction; 30 nM LY354740
& 30 MUM LY487379: 34.6 +/- 5.2% reduction). We then showed activation of mGlu2
receptors on astrocytes: astrocytic intracellular calcium levels were elevated by
the Group II agonist, which were further potentiated upon mGlu2 PAM co
application (300 nM LY354740: ratio amplitude 0.016 +/- 0.002; 300 nM LY354740 &
30 MUM LY487379: ratio amplitude 0.035 +/- 0.003). We then demonstrated mGlu2
dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses
to vibrissae stimulation trains were disinhibited by the Group II agonist and the
mGlu2 PAM (LY354740: 156 +/- 12% of control; LY487379: 144 +/- 10% of control).
Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91
+/- 5% of control), suggesting the mGlu2 component to the Group II effect can be
attributed to activation of mGlu2 receptors localised on astrocytic processes
within the VB. Gating of thalamocortical function via astrocyte activation
represents a novel sensory processing mechanism. As this thalamocortical
circuitry is important in discriminative processes, this demonstrates the
importance of astrocytes in synaptic processes underlying attention and
cognition.
PMID- 28416445
TI - alphaO-Conotoxin GeXIVA disulfide bond isomers exhibit differential sensitivity
for various nicotinic acetylcholine receptors but retain potency and selectivity
for the human alpha9alpha10 subtype.
AB - Nicotinic acetylcholine receptor (nAChR) subtypes exhibit distinct
neuropharmacological properties that are involved in a range of neuropathological
conditions, including pain, addiction, epilepsy, autism, schizophrenia,
Tourette's syndrome, Alzheimer's and Parkinson's diseases, as well as many types
of cancer. The alpha9alpha10 nAChR is a potential target in chronic pain, wound
healing, the pathophysiology of the auditory system, and breast and lung cancers.
alphaO-conotoxin GeXIVA is a potent antagonist of rat alpha9alpha10 nAChRs, with
the 'bead' disulfide bond isomer displaying the lowest IC50 of the three possible
isomers. In the rat chronic constriction injury model of neuropathic pain, this
isomer reduced mechanical hyperalgesia without affecting motor performance. Here,
we report the effects of the three disulfide bond isomers of GeXIVA on human
alpha9alpha10 nAChRs, other human nAChR subtypes, various rat nAChR subtypes, and
10 rat alpha9alpha10 nAChR mutants. The three isomers displayed only ~5-fold
difference in potency on the human vs rat alpha9alpha10 receptors and had similar
affinities at wild-type rat alpha9alpha10 nAChRs and all 10 alpha9alpha10
receptor mutants. From these findings, the binding site and mechanism of action
of GeXIVA on rat and human alpha9alpha10 nAChR was deduced to be different from
that of other conotoxins targeting this nAChR subtype. GeXIVA is therefore a
unique ligand that might prove useful for further probing of binding sites on the
alpha9alpha10 nAChR. This article is part of the Special Issue entitled 'Venom
derived Peptides as Pharmacological Tools.'
PMID- 28416447
TI - Evolutionary Origins of cGAS-STING Signaling.
AB - Detection of foreign nucleic acids is an important strategy for innate immune
recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the
cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger
cGAMP to activate the signaling adaptor STING. While induction of antiviral type
I interferons (IFNs) is the major outcome of STING activation in vertebrates, it
has recently become clear that core components of the cGAS-STING pathway evolved
more than 600 million years ago, predating the evolution of type I IFNs. Here we
discuss the evolutionary origins of the cGAS-STING pathway, and consider the
possibility that the ancestral functions of STING may have included activation of
antibacterial immunity.
PMID- 28416446
TI - Patterns, Receptors, and Signals: Regulation of Phagosome Maturation.
AB - Recognition of microbial pathogens and dead cells and their phagocytic uptake by
specialized immune cells are essential to maintain host homeostasis. Phagosomes
undergo fusion and fission events with endosomal and lysosomal compartments, a
process called 'phagosome maturation', which leads to the degradation of the
phagosomal content. However, many phagocytic cells also act as antigen-presenting
cells and must balance degradation and peptide preservation. Emerging evidence
indicates that receptor engagement by phagosomal cargo, as well as inflammatory
mediators and cellular activation affect many aspects of phagosome maturation.
Unsurprisingly, pathogens have developed strategies to hijack this machinery,
thereby interfering with host immunity. Here, we highlight progress in this
field, summarize findings on the impact of immune signals, and discuss
consequences for pathogen elimination.
PMID- 28416448
TI - Immunological Memory of Group 2 Innate Lymphoid Cells.
AB - Immunological memory has long been described as a property of the adaptive immune
system that results in potent responses on exposure to an antigen encountered
previously. While this definition appears to exclude cells that do not express
antigen receptors, recent studies have shown that innate immune cells, including
natural killer (NK) cells, macrophages, and, more recently, group 2 innate
lymphoid cells (ILC2s) can record previous activations and respond more
vigorously on reactivation. Here we review the similarities and differences
between these forms of memory and the underlying mechanisms. Based on these
insights, we propose to revise the definition of immunological memory, as the
capacity to remember being previously activated and respond more efficiently on
reactivation regardless of antigen specificity.
PMID- 28416449
TI - Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence
Based Discovery.
AB - Complement dysregulation underlies several inflammatory disorders, and terminal
complement inhibition has thus far afforded significant clinical gains.
Nonetheless, emerging pathologies, fueled by complement imbalance and therapy
skewing genetic variance, underscore the need for more comprehensive, disease
tailored interventions. Modulation at the level of C3, a multifaceted
orchestrator of the complement cascade, opens up prospects for broader
therapeutic efficacy by targeting multiple pathogenic pathways modulated by C3
triggered proinflammatory crosstalk. Notably, C3 intervention is emerging as a
viable therapeutic strategy for renal disorders with predominantly complement
driven etiology, such as C3 glomerulopathy (C3G). Using C3G as a paradigm, we
argue that concerns about the feasibility of long-term C3 intervention need to be
placed into perspective and weighed against actual therapeutic outcomes in
prospective clinical trials.
PMID- 28416450
TI - Denoise diffusion-weighted images using higher-order singular value
decomposition.
AB - Noise usually affects the reliability of quantitative analysis in diffusion
weighted (DW) magnetic resonance imaging (MRI), especially at high b-values
and/or high spatial resolution. Higher-order singular value decomposition (HOSVD)
has recently emerged as a simple, effective, and adaptive transform to exploit
sparseness within multidimensional data. In particular, the patch-based HOSVD
denoising has demonstrated superb performance when applied to T1-, T2-, and
proton density-weighted MRI data. In this study, we aim to investigate the
feasibility of denoising DW data using the HOSVD transform. With the low signal
to-noise ratio in typical DW data, the patch-based HOSVD denoising suffers from
stripe artifacts in homogeneous regions because of the HOSVD bases learned from
the noisy patches. To address this problem, we propose a novel denoising method.
It first introduces a global HOSVD-based denoising as a prefiltering stage to
guide the subsequent patch-based HOSVD denoising stage. The HOSVD bases from the
patch groups in prefiltered images are then used to transform the noisy patch
groups in original DW data. Experiments were performed using simulated and in
vivo DW data. Results show that the proposed method significantly reduces stripe
artifacts compared with conventional patch-based HOSVD denoising methods, and
outperforms two state-of-the-art denoising methods in terms of denoising quality
and diffusion parameters estimation.
PMID- 28416451
TI - Diffeomorphic functional brain surface alignment: Functional demons.
AB - Aligning brain structures across individuals is a central prerequisite for
comparative neuroimaging studies. Typically, registration approaches assume a
strong association between the features used for alignment, such as macro
anatomy, and the variable observed, such as functional activation or
connectivity. Here, we propose to use the structure of intrinsic resting state
fMRI signal correlation patterns as a basis for alignment of the cortex in
functional studies. Rather than assuming the spatial correspondence of functional
structures between subjects, we have identified locations with similar
connectivity profiles across subjects. We mapped functional connectivity
relationships within the brain into an embedding space, and aligned the resulting
maps of multiple subjects. We then performed a diffeomorphic alignment of the
cortical surfaces, driven by the corresponding features in the joint embedding
space. Results show that functional alignment based on resting state fMRI
identifies functionally homologous regions across individuals with higher
accuracy than alignment based on the spatial correspondence of anatomy. Further,
functional alignment enables measurement of the strength of the anatomo
functional link across the cortex, and reveals the uneven distribution of this
link. Stronger anatomo-functional dissociation was found in higher association
areas compared to primary sensory- and motor areas. Functional alignment based on
resting state features improves group analysis of task based functional MRI data,
increasing statistical power and improving the delineation of task-specific core
regions. Finally, a comparison of the anatomo-functional dissociation between
cohorts is demonstrated with a group of left and right handed subjects.
PMID- 28416452
TI - Associated motivational salience impacts early sensory processing of human faces.
AB - Facial expressions of emotion have an undeniable processing advantage over
neutral faces, discernible both at behavioral level and in emotion-related
modulations of several event-related potentials (ERPs). Recently it was proposed
that also inherently neutral stimuli might gain salience through associative
learning mechanisms. The present study investigated whether acquired motivational
salience leads to processing advantages similar to biologically determined
origins of inherent emotional salience by applying an associative learning
paradigm to human face processing. Participants (N=24) were trained to categorize
neutral faces to salience categories by receiving different monetary outcomes.
ERPs were recorded in a subsequent test phase consisting of gender decisions on
previously associated faces, as well as on familiarized and novel faces
expressing happy, angry or no emotion. Previously reward-associated faces boosted
the P1 component, indicating that acquired reward-associations modulate early
sensory processing in extrastriate visual cortex. However, ERP modulations to
emotional - primarily angry - expressions expanded to subsequent processing
stages, as reflected in well-established emotion-related ERPs. The present study
offers new evidence that motivational salience associated to inherently neutral
stimuli can sharpen sensory encoding but does not obligatorily lead to
preferential processing at later stages.
PMID- 28416453
TI - High resolution data analysis strategies for mesoscale human functional MRI at 7
and 9.4T.
AB - The advent of ultra-high field functional magnetic resonance imaging (fMRI) has
greatly facilitated submillimeter resolution acquisitions (voxel volume below
(1mm3)), allowing the investigation of cortical columns and cortical depth
dependent (i.e. laminar) structures in the human brain. Advanced data analysis
techniques are essential to exploit the information in high resolution functional
measures. In this article, we use recent, exemplary 9.4T human functional and
anatomical data to review the advantages and disadvantages of (1) pooling high
resolution data across regions of interest for cortical depth profile analysis,
(2) pooling across cortical depths for mapping patches of cortex while discarding
depth-dependent (i.e. columnar) effects, and (3) isotropic sampling without
pooling to assess individual voxel's responses. A set of cortical depth meshes
may be a solution to sampling information tangentially while keeping
correspondence across depths. For quantitative analysis of the spatial
organization in fine-grained structures, a cortical grid approach is
advantageous. We further extend this general framework by combining it with a
previously introduced cortical layer volume-preserving (equi-volume) approach.
This framework can readily accommodate the research questions which allow for
spatial smoothing within or across layers. We demonstrate and discuss that equi
volume sampling yields a slight advantage over equidistant sampling given the
current limitations of fMRI voxel size, participant motion, coregistration and
segmentation. Our 9.4T human anatomical and functional data indicate the
advantage over lower fields including 7T and demonstrate the practical
applicability of T2* and T2-weighted fMRI acquisitions.
PMID- 28416454
TI - E1a is an exogenous in vivo tumour suppressor.
AB - The E1a gene from adenovirus has become a major tool in cancer research. Since
the discovery of E1a, it has been proposed to be an oncogene, becoming a key
element in the model of cooperation between oncogenes. However, E1a's in vivo
behaviour is consistent with a tumour suppressor gene, due to the block/delay
observed in different xenograft models. To clarify this interesting controversy,
we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo.
Initially, a conventional xenograft approach was performed using previously
unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect
regardless of the mouse's immunological background
(immunosuppressed/immunocompetent). Next, we engineered a transgenic mouse model
in which inducible E1a 13s expression was under the control of cytokeratin 5 to
avoid side effects during embryonic development. Our results show that E1a is
able to block chemical skin carcinogenesis, showing an anti-tumour effect. The
present report demonstrates the in vivo anti-tumour effect of E1a, showing that
the in vitro oncogenic role of E1a cannot be extrapolated in vivo, supporting its
future use in gene therapy approaches.
PMID- 28416455
TI - Protection from Cr(VI)-induced malignant cell transformation and tumorigenesis of
Cr(VI)-transformed cells by luteolin through Nrf2 signaling.
AB - Cr(VI) is a well known environmental carcinogen, but its mechanism of action and
the measures required to mitigate its effects remain to be investigated. Our
previous studies showed that exposure of human bronchial epithelial (BEAS-2B)
cells to Cr(VI) caused malignant transformation, that these transformed cells
progressed through tumorigenesis, and that luteolin, a natural compound,
inhibited both of these processes. The present study investigates the underlying
mechanisms by which luteolin protects cells against Cr(VI)-induced transformation
and tumorigenesis. The present study shows that luteolin activates inducible Nrf2
to inhibit Cr(VI)-generated reactive oxygen species (ROS) in normal BEAS-2B
cells. The decreased ROS level is likely responsible for the protective effect of
luteolin against Cr(VI)-induced malignant cell transformation in normal cells. By
contrast, in cells that have been transformed by Cr(VI), Nrf2 is constitutively
activated, and its target proteins, heme oxygenase 1 (HO-1), NAD(P)H:quinone
oxidoreductase 1 (NQO1), and superoxide dismutase 1/2 (SOD1/SOD2) are all
constitutively activated, and ROS levels are low. Bcl-2, an anti-apoptotic
protein and target protein of Nrf2 is elevated. Cr(VI)-transformed BEAS-2B cells
develop apoptosis resistance, increasing the survival of these transformed cells.
Luteolin decreases interactions between Nrf2 and the antioxidant response element
sites of its target anti-apoptotic and antioxidant proteins, Bcl-2, Bcl-XL, and
HO-1, which results in decreased constitutive Nrf2 activation. The decreased
constitutive Nrf2 activation, decrease in Nrf2 target proteins and consequent
apoptosis resistance by luteolin are possible mechanisms that mediate the
protective effect of luteolin in Cr(VI)-transformed cells.
PMID- 28416456
TI - Licoricidin inhibits the growth of SW480 human colorectal adenocarcinoma cells in
vitro and in vivo by inducing cycle arrest, apoptosis and autophagy.
AB - Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer
activities, but the active ingredients and underlying mechanisms have not been
revealed. By screening the cytotoxic activities of 122 licorice compounds against
SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD)
inhibited SW480 cell viability with an IC50 value of 7.2MUM. Further studies
indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in
SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation
of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy
in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway.
Overexpression of a dominant-negative AMPKalpha2 abolished LCD-induced inhibition
of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly
reversed loss of cell viability, suggesting activation of AMPK is essential for
the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that
LCD (20mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in
nude mice with an inhibitory rate of 43.5%. In addition, we obtained the
glycosylated product LCDG by microbial transformation, and found that
glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This
study indicates that LCD could inhibit SW480 cells by inducing cycle arrest,
apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic
agent against colorectal cancer.
PMID- 28416457
TI - Mono-2-ethylhexyl phthalate inhibits human extravillous trophoblast invasion via
the PPARgamma pathway.
AB - Concerns over the adverse reproductive outcomes in human have been raised, more
evidence including the underlying mechanism are required. Since extravillous
trophoblast (EVT) invasion is an important physiological step during early
development, the effects of mono-2-ethylhexyl phthalate (MEHP), the bioactive
metabolite of DEHP, on EVT invasion were investigated using Matrigel-coated
transwell chambers and cell line HTR-8/SVneo. In the transwell-based invasive
assay, MEHP exposure inhibited EVT invasion as judged by decreased invasion
index. Further analysis showed that MEHP exposure significantly inhibited the
activity of matrix metalloproteinase-9 (MMP-9), which is an important positive
regulator of EVT invasion. Meanwhile, the protein levels of tissue inhibitor
matrix metalloproteinase-1 (TIMP-1), one key negative regulator of EVT invasion,
were upregulated by MEHP treatment. Finally, inactivation of PPARgamma pathway by
either PPARgamma inhibitors or PPARgamma shRNA knockdown rescued the MEHP-induced
inhibited invasion of HTR-8/SVneo cells, which is accompanied by the recovery of
inhibited MMP-9 expression. The present study provides the evidence that MEHP
exposure inhibits trophoblast invasion via PPARgamma at concentrations comparable
to those found in humans, which provides an insight in understanding the
mechanisms of DEHP-associated early pregnancy loss.
PMID- 28416458
TI - On the origins of sex-based differences in respiratory disorders: Lessons and
hypotheses from stress neuroendocrinology in developing rats.
AB - The environment plays a critical role in shaping development and function of the
brain. Stress, especially when experienced early in life, can interfere with
these processes. In the context of respiratory control, perinatal stress can
therefore alter the ability to achieve the "fine-tuning" necessary for proper
detection of chemosensory stimuli and production of an adequate motor
(respiratory) command. Depending on the timing, intensity, and duration, the
detrimental consequences of perinatal exposure to adverse conditions on the
respiratory network become manifest at various life stages and can persist into
adulthood. During early life, respiratory diseases commonly associated with
dysfunction of neural networks include apnea of prematurity (AOP) and cardio
respiratory failure leading to sudden infant death syndrome (SIDS). Sleep
disordered breathing (SDB) can occur at various life stages, including adulthood.
Regardless of age, a common element of these disorders is their greater
prevalence in males. While this sexual dimorphism points to a potential role of
sex hormones, our understanding of the neuroendocrine mechanisms remain poorly
understood. In addition to their modulatory influence on breathing, gonadal
hormones regulate sexual differentiation of the brain. Stress alters these
effects, and over the years our laboratory has used various perinatal stress
protocols to gain insight into the origins of sex-based differences in
respiratory disorders. This review discusses our recent advances with a focus on
the sex-specific impact of early life stress on O2-chemoreflex function both in
newborn and adult rats. We conclude by discussing the basic principles emerging
from this work, potential mechanisms, and clinical relevance.
PMID- 28416459
TI - The error of Broca: From the traditional localizationist concept to a connectomal
anatomy of human brain.
AB - Neurology, especially aphasiology, was mainly built on behavioral-structural
correlations ("lesion method"). In this setting, Broca's area has been considered
as the "speech area"; moreover, this observation led to localizationism. However,
advances in brain mapping techniques, as functional neuroimaging and direct
electrical stimulation in patients undergoing awake surgery for gliomas, has
resulted in a paradigmatic shift regarding models of neural architecture. In
fact, the brain is organized in distributed complex networks underpinning
sensorimotor, visuospatial, language, cognitive and emotional functions. In this
connectomal workframe, cerebral processing is not conceived as the sum of
segregated subfunctions, but results from the integration and potentiation of
parallel (even if partially overlapped) subcircuits. Such a networking model,
taking into account cortical and subcortical anatomic constraints, explains
interindividual variability in physiology and after brain damage, particularly in
aphasiology - e.g. double dissociations during electrostimulations, as
comprehension versus naming disorders, semantic versus phonemic paraphasias, or
syntactic disturbances versus anomia. This dynamic organization mediated by the
well-synchronized functioning of delocalized groups of interconnected neurons
(rather than by discrete centers) also explains the huge potential of
neuroplasticity following cerebral insult, on the condition that the axonal
connectivity is preserved. According to this principle, massive surgical
resection of brain regions dogmatically considered as "critical" in a
localisationist view can be achieved with no functional deficit, as the removal
of Broca's area - which is not the speech area - without disorders. This
connectomal account of neural processing may have major implications in cognitive
neurosciences and in therapeutic management of brain-damaged patients.
PMID- 28416460
TI - Regional distribution of cholinergic, catecholaminergic, serotonergic and
orexinergic neurons in the brain of two carnivore species: The feliform banded
mongoose (Mungos mungo) and the caniform domestic ferret (Mustela putorius furo).
AB - The nuclear organization of the cholinergic, catecholaminergic, serotonergic and
orexinergic neurons in the brains of two species of carnivore, the banded
mongoose (Mungos mungo) and domestic ferret (Mustela putorius furo), is
presented. The banded mongoose belongs to the feliform suborder and the domestic
ferret to the caniform suborder, having last shared a common ancestor
approximately 53 million years ago; however, they have a very similar overall
morphology and life history, presenting an interesting opportunity to examine the
extent of evolutionary plasticity in these systems. The brains of the two
carnivore species were coronally sectioned and immunohistochemically stained with
antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and
orexin-A. The overall organization and complement of the nuclei of these systems
was identical between the two species, although minor differences were noted.
Moreover, this overall organization is identical to other studies undertaken in
the domestic cat and dog. While for the most part the nuclei forming these
systems are similar to those observed in other mammals, two species differences,
which appear to be carnivore-specific, were noted. First, cholinergic neurons
were observed in the lateral septal nucleus of both species, an apparently
carnivore specific feature not recorded previously in other mammals. Second, the
serotonergic neurons of the peripheral division of the dorsal raphe complex
exhibited a significant caudad expansion, intermingling with the cholinergic and
catecholaminergic nuclei of the pons, a carnivore specific feature. These
carnivore specific features likely have functional consequences related to coping
with stress and the expression of sleep.
PMID- 28416462
TI - Clinical assessment of 115 cases of hindfoot fusion with two different types of
graft: Allograft+DBM+bone marrow aspirate versus autograft+DBM.
AB - INTRODUCTION: Nonunion is a common complication (15%) of hindfoot and ankle
arthrodesis. Autograft can improve the fusion rate because of its
osteoconductive, osteoinductive and osteogenic properties. However, autograft
harvesting is a source of morbidity. One alternative is to combine allograft with
demineralized bone matrix (DBM) and iliac bone marrow aspirate (BMA). This
combination graft has similar biological properties to healthy bone. When used
alone, allograft has osteoconductive and sometimes structural properties. DBM
provides osteoinduction and improves the osteconductivity. BMA adds cells and
thereby osteogenic potential. HYPOTHESIS: Given its intrinsic properties,
allograft-DBM-BMA is as effective as autograft-DBM treatment while simplifying
the clinical practice. MATERIAL AND METHODS: One hundred and fifteen cases of
ankle and hindfoot arthrodesis were studied in 82 patients divided in two groups:
autograft-DBM vs allograft-DBM-BMA. Treatment effectiveness was assessed using
clinical (time to fusion, fusion rate) and radiological (trabecular bone bridge,
disappearance of joint space) criteria. A CT scan was done in 60% of cases when
fusion could not be confirmed using the clinical and radiological criteria.
RESULTS: There was no significant difference between the two groups in terms of
fusion rate, time to fusion, number of heterotopic ossifications, revision rate
and quantity of DBM used. The nonunion rate was 18% in the autograft group and
13% in the allograft group. The infection rate was 11% in the autograft and 4% in
the allograft group. DISCUSSION: Allograft-DBM-BMA is an alternative to autograft
DBM that provides similar effectiveness without increasing the number of nonunion
or complications. Osteonecrosis and surgical revision are risk factors. LEVEL OF
EVIDENCE: III retrospective study.
PMID- 28416461
TI - Detection of penetration of the dorsal cortex by epiphyseal screws of distal
radius volar plates: Anatomical study comparing ultrasound and fluoroscopy.
AB - HYPOTHESIS: Osteosynthesis of the distal radius by a volar plate can be
complicated by lesions of extensor tendons by screws penetrating the dorsal
cortex. The fluoroscopic skyline view enables to confirm the length of the
screws. To avoid its risk of irradiation, some authors have recommended using
ultrasound instead. MATERIAL AND METHODS: The goal of this study was to
demonstrate that the detection rate of screws penetrating the dorsal cortex was
at least as good using ultrasound compared to fluoroscopic skyline. A volar plate
in which one screw penetrated the dorsal cortex was implanted in 10 cadaveric
wrists. Three observers had to detect which screw penetrated the dorsal cortex
using ultrasound and then a fluoroscopic skyline. RESULTS: The detection rate of
screws penetrating the dorsal cortex was 43.33% with ultrasound and 96.97% using
the fluoroscopic skyline. Agreement between the observers was poor with
ultrasound and good with fluoroscopy. CONCLUSION: Our results show that
ultrasound cannot replace the fluoroscopic skyline view to detect screws
penetrating the dorsal cortex of the distal radius in clinical practice. LEVEL OF
EVIDENCE: II.
PMID- 28416463
TI - Glucocorticoids activate a synapse weakening pathway culminating in tau
phosphorylation in the hippocampus.
AB - Evidence suggests that the stress hormones glucocorticoids (GCs) can cause
cognitive deficits and neurodegeneration. Previous studies have found GCs
facilitate physiological synapse weakening, termed long-term depression (LTD),
though the precise mechanisms underlying this are poorly understood. Here we show
that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse
weakening signals. Critically, this ultimately leads to phosphorylation of the
microtubule associated protein tau, specifically at the serine 396 residue, and
this is a causal factor in the GC-mediated impairment of synaptic function. These
findings reveal the link between GCs and synapse weakening signals, and the
potential for stress-induced priming of neurodegeneration. This could have
important implications for our understanding of how stress can lead to
neurodegenerative disease.
PMID- 28416464
TI - Microbiological quality of water in a city with persistent and recurrent
waterborne diseases under tropical sub-rural conditions: The case of Kikwit City,
Democratic Republic of the Congo.
AB - The availability of safe drinking water in sub-Saharan countries remains a major
challenge because poor sanitation has been the cause of various outbreaks of
waterborne disease due to the poor microbiological quality of water used for
domestic purposes. The faecal indicator bacteria (FIB) used in the present study
included Escherichia coli (E. coli) and Enterococcus (ENT). FIB and aerobic
mesophilic bacteria (AMB) were quantified during July 2015 (dry season) and
November 2015 (rainy season) in order to assess the quality of drinking water
from wells (n=3; P1-P3), and two rivers, the River Lukemi (RLK, n=3) and River
Luini (RLN, n=2) in the city of Kikwit, which is located in the province of Kwilu
in the Democratic Republic of the Congo. Kikwit is well known for its outbreaks
of persistent and recurrent waterborne diseases including Entamoeba, Shigella,
typhoid fever, cholera, and Ebola Viral Hemorrhagic Fever. Consequently, E. coli,
ENT, and AMB were quantified in water samples according to the standard
international methods for water quality determination using the membrane
filtration method. The FIB characterization was performed for human-specific
Bacteroides by PCR using specific primers. The results obtained revealed high FIB
concentrations in river samples collected during both seasons. For example, E.
coli respectively reached 4.3*104 and 9.2*104 CFU 100mL-1 in the dry season and
the wet season. ENT reached 5.3*103 CFU 100mL-1 during the dry season and 9.8*103
CFU 100mL-1 in the wet season. The pollution was significantly worse in the wet
season compared to the dry season. Surprisingly, no faecal contamination was
observed in well water samples collected in the dry season while E. coli and ENT
were detected in all wells in the wet season with values of 6, 7, and 11CFUmL-1
for E. coli in wells P1-P3, respectively and 3, 5, 9 CFU mL-1for ENT in the same
wells. Interestingly, the PCR assays for human-specific Bacteroides HF183/HF134
indicated that 97-100% captured in all analyses of isolated FIB were of human
origin. The results indicate that contamination of E. coli, ENT, and AMB in the
studied water resources increases during the wet season. This study improves
understanding of the microbiological pollution of rivers and wells under tropical
conditions and will guide future municipal/local government decisions on
improving water quality in this region which is characterised by persistent and
recurrent waterborne diseases. Although the epidemiology can be geographically
localised, the effects of cross border transmission can be global. Therefore, the
research results presented in this article form recommendations to
municipalities/local authorities and the approach and procedures can be carried
out in a similar environment.
PMID- 28416465
TI - 15 years of monitoring occupational exposure to respirable dust and quartz within
the European industrial minerals sector.
AB - INTRODUCTION: In 2000, a prospective Dust Monitoring Program (DMP) was started in
which measurements of worker's exposure to respirable dust and quartz are
collected in member companies from the European Industrial Minerals Association
(IMA-Europe). After 15 years, the resulting IMA-DMP database allows a detailed
overview of exposure levels of respirable dust and quartz over time within this
industrial sector. Our aim is to describe the IMA-DMP and the current state of
the corresponding database which due to continuation of the IMA-DMP is still
growing. The future use of the database will also be highlighted including its
utility for the industrial minerals producing sector. METHODS: Exposure data are
being obtained following a common protocol including a standardized sampling
strategy, standardized sampling and analytical methods and a data management
system. Following strict quality control procedures, exposure data are
consequently added to a central database. The data comprises personal exposure
measurements including auxiliary information on work and other conditions during
sampling. RESULTS: Currently, the IMA-DMP database consists of almost 28,000
personal measurements which have been performed from 2000 until 2015 representing
29 half-yearly sampling campaigns. The exposure data have been collected from 160
different worksites owned by 35 industrial mineral companies and comes from 23
European countries and approximately 5000 workers. CONCLUSION: The IMA-DMP
database provides the European minerals sector with reliable data regarding
worker personal exposures to respirable dust and quartz. The database can be used
as a powerful tool to address outstanding scientific issues on long-term exposure
trends and exposure variability, and importantly, as a surveillance tool to
evaluate exposure control measures. The database will be valuable for future
epidemiological studies on respiratory health effects and will allow for
estimation of quantitative exposure response relationships.
PMID- 28416466
TI - Risk of atrioesophageal fistula formation with contact force-sensing catheters.
AB - BACKGROUND: Atrioesophageal fistula formation is a rare but life-threatening
complication of atrial fibrillation ablation. Contact force (CF)-sensing
catheters improve procedural effectiveness. However, the impact of the
implementation of CF-sensing technology on the risk of atrioesophageal fistula
formation has not been explored. OBJECTIVE: The purpose of this study was to
determine the association between the use of CF-sensing catheters and
atrioesophageal fistula development. METHODS: We searched the Manufacturer and
User Facility Device Experience database for adverse event reports involving Food
and Drug Administration-approved ablation catheters. RESULTS: Among 2689 device
reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF
sensing catheters and 13 non-CF-sensing catheters. The percentage of total
reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65
of 1202) and 0.9% for non-CF-sensing catheters (13 of 1487) (P < .0001).
Procedural details (CF and power settings) were not consistently reported.
Esophageal temperature increases were detected in only 2.5% of cases (2 of 78).
The mean time to presentation was 16 +/- 9 days. Overall mortality was at least
56%, with patients who underwent surgical repair more likely to survive than
those treated with stenting or no intervention. CONCLUSION: Atrioesophageal
fistula formation accounted for a much higher proportion of reported adverse
events with CF-sensing catheters compared with non-CF-sensing catheters. Improved
understanding of the relationship between power/force delivery and esophageal
damage is needed to minimize the risk of atrioesophageal fistula formation.
PMID- 28416467
TI - Early repolarization is associated with a significantly increased risk of
ventricular arrhythmias and sudden cardiac death in patients with structural
heart diseases.
AB - BACKGROUND: Early repolarization pattern (ERP) has been proved to increase risk
of arrhythmia death in the general population, but its prognostic significance in
patients with structural heart disease (SHD) is controversial. OBJECTIVE: The
purpose of this study was to conduct a meta-analysis of studies assessing the
association between ERP and risk of ventricular arrhythmias (VTAs) and sudden
cardiac death (SCD) in patients with SHD. METHODS: We performed a literature
search using MEDLINE (January 1, 1966, to September 25, 2016) and EMBASE (January
1, 1980, to September 25, 2016) with no restrictions. Studies that reported odds
ratio (OR) estimates with 95% confidence intervals (CIs) for the associations of
interest were included. RESULTS: The search yielded 19 observational studies,
involving 7268 patients that reported 1127 cases of VTAs or SCD. In the selected
studies, the point estimates of the ORs were consistently greater than 1.
Compared with those without ERP, patients with ERP experienced a significantly
increased risk of developing VTAs or SCD (OR 4.76; 95% CI 3.62-6.26), ventricular
fibrillation (OR 7.14; 95% CI 4.31-11.82), and SCD (OR 4.07; 95% CI 1.58-10.51).
The results were consistent and statistically significant in all subgroups. ERP
with J-point elevation in inferior leads, notching configuration, and horizontal
or descending ST segment connote higher risk. CONCLUSION: ERP is associated with
a significant increased risk of VTAs or SCD in patients with SHD. Future research
should attempt to understand the exact mechanisms for the arrhythmia risk and to
introduce ERP in the risk stratification in this patient group.
PMID- 28416468
TI - Cardiac transplantation in children and adolescents with long QT syndrome.
AB - BACKGROUND: Long QT syndrome (LQTS) is a potentially lethal, yet highly
treatable, cardiac channelopathy. Cardiac transplantation has been reported
anecdotally for patients with severe LQTS refractory to standard therapies.
OBJECTIVE: The purpose of this study was to evaluate the incidence of and risk
factors for cardiac transplantation in children evaluated and treated in an LQTS
specialty center. METHODS: This was a retrospective review of 349 children with
LQTS (mean age at diagnosis, 8.0 +/- 5.7 years; mean corrected QT interval, 469
+/- 51 ms; long QT syndrome type 1 [LQT1] in 46%, LQT2 in 31%, and LQT3 in 9%)
evaluated from 2000 to 2013. A subset analysis was performed on patients referred
for cardiac transplantation. RESULTS: Only 3 patients (0.9%; all LQT3; 2 female)
underwent cardiac transplantation at ages 4, 11, and 17 years. Overall, 90 of 349
(26%) were symptomatic (exhibited LQTS-associated cardiac events) before LQTS
diagnosis, including those who ultimately underwent transplant. Age at sentinel
event was associated with transplantation (3 of 26 [12%] with an event at <1 year
of life were transplanted vs 0 of 64 with an event after age 1; P = .02).
Genotype was also a risk factor (3 of 32 patients with LQT3 were transplanted
[9.4%] vs 0 of 270 patients with LQT1 or LQT2; P = .001). Before transplant, all
patients had recurrent ventricular fibrillation-terminating shocks despite
combination drug therapy and bilateral sympathetic denervation. All transplanted
patients are alive at follow-up. CONCLUSION: Cardiac transplantation is seldom
necessary for the management of LQTS. However, patients with LQT3 and in
utero/neonatal expressivity are at higher risk of treatment failure and
refractory ventricular arrhythmias with standard therapy, and cardiac
transplantation should be considered for this malignant subset of LQTS.
PMID- 28416470
TI - Block ionomer micellar nanoparticles from double hydrophilic copolymers,
classifications and promises for delivery of cancer chemotherapeutics.
AB - A class of double hydrophilic copolymers comprising ionic and nonionic water
soluble blocks, which are also called block ionomers, represent an interesting
type of polymer assembly forming stable, homogeneous core-corona dispersions.
They exhibit the solution behavior of normal polyelectrolytes, whereas assembly
into micelle, vesicle or disk morphology happens by an external stimulus (pH,
temperature or ionic strength) or complex formation with metal ions, ionic
surfactants, polyelectrolytes, etc. Temperature, pH, redox or salt sensitivity
affords a unique opportunity to control the triggered release of payloads
accommodated through electrostatic interaction, coordination or chemical
conjugation. Moreover, the non-ionic block provides the surface passivation,
prolongation of the blood circulation and tumor accumulation, supporting targeted
delivery of chemotherapeutic agents based on pathophysiology of tumor
microenvironment. Potentiation of antitumor activity, sensitization of the
resistant tumors, increased tolerated dose and translation into clinical practice
are among their most intriguing characteristics. Their high functionality has
been suggested for co-delivery of multiple agents for reversal of chemo
resistance as well as simultaneous therapy and diagnostics. Nevertheless, some
stability concerns may be raised due to the polymer disassembly beyond a critical
concentration of pH, salt and polyion concentration that can be modulated by
introducing crosslinks between the polymer chains (Nano-networks).
PMID- 28416472
TI - Oesophageal cancer presenting as Lemierre's syndrome caused by Streptococcus
anginosus.
AB - A 59-year-old man presented to the emergency department with complaints of
dysphagia, right-sided neck swelling, fever and chills. Physical examination was
remarkable for fever and tender swelling over the right side of the neck.
Laboratory investigations revealed leucocytosis with neutrophilia. CT of the neck
showed right internal jugular vein thrombosis with an overlying abscess and a
nodular opacity in the right lung apex with air locules. He underwent surgical
drainage of the neck abscess. Aerobic cultures from the drainage and blood
cultures grew Streptococcus anginosus Given his initial complaint of dysphagia,
upper endoscopy was performed which showed a mass in the upper oesophagus.
Histopathology confirmed squamous cell carcinoma. The patient received 6 weeks of
antibiotics therapy.
PMID- 28416473
TI - Ollier's disease: features of the hands.
PMID- 28416474
TI - Posterior reversible encephalopathy in an adult patient with poststreptococcal
glomerulonephritis.
PMID- 28416471
TI - Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for
Leukemic Stem Cells but Require Oxidative Metabolism.
AB - Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be
enriched in quiescent immature leukemic stem cells (LSC). To validate this
hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach
treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual
AML cells are enriched in neither immature, quiescent cells nor LSCs. Strikingly,
AraC-resistant preexisting and persisting cells displayed high levels of reactive
oxygen species, showed increased mitochondrial mass, and retained active
polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS)
status. AraC residual cells exhibited increased fatty-acid oxidation, upregulated
CD36 expression, and a high OXPHOS gene signature predictive for treatment
response in PDX and patients with AML. High OXPHOS but not low OXPHOS human AML
cell lines were chemoresistant in vivo. Targeting mitochondrial protein
synthesis, electron transfer, or fatty-acid oxidation induced an energetic shift
toward low OXPHOS and markedly enhanced antileukemic effects of AraC. Together,
this study demonstrates that essential mitochondrial functions contribute to AraC
resistance in AML and are a robust hallmark of AraC sensitivity and a promising
therapeutic avenue to treat AML residual disease.Significance: AraC-resistant AML
cells exhibit metabolic features and gene signatures consistent with a high
OXPHOS status. In these cells, targeting mitochondrial metabolism through the
CD36-FAO-OXPHOS axis induces an energetic shift toward low OXPHOS and strongly
enhanced antileukemic effects of AraC, offering a promising avenue to design new
therapeutic strategies and fight AraC resistance in AML. Cancer Discov; 7(7); 716
35. (c)2017 AACR.See related commentary by Schimmer, p. 670This article is
highlighted in the In This Issue feature, p. 653.
PMID- 28416475
TI - Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2
Diabetes: A Case Series.
PMID- 28416477
TI - Actin filament assembly by bacterial factors VopL/F: Which end is up?
AB - Competing models have been proposed for actin filament nucleation by the
bacterial proteins VopL/F. In this issue, Burke et al. (2017. J. Cell Biol.
https://doi.org/10.1083/jcb.201608104) use direct observation to demonstrate that
VopL/F bind the barbed and pointed ends of actin filaments but only nucleate new
filaments from the pointed end.
PMID- 28416478
TI - Stardust, the Janus-faced partner of Crumbs.
AB - The Drosophila melanogaster scaffolding protein Stardust (Sdt) stabilizes the
transmembrane protein Crumbs, a conserved regulator of apical-basal epithelial
polarity. In this issue, Perez-Mockus et al. (2017. J. Cell Biol
https://doi.org/10.1083/jcb.201611196) report that a subset of Sdt isoforms are
targeted by the ubiquitin ligase Neuralized, thus fine tuning the endocytosis and
activity of this apical determinant.
PMID- 28416480
TI - Correction to: Atypical presentation of a spontaneous celiac artery dissection
resulting in jejuna ischaemia.
PMID- 28416479
TI - Suppression of integrin alpha3beta1 by alpha9beta1 in the epidermis controls the
paracrine resolution of wound angiogenesis.
AB - Development of wound therapies is hindered by poor understanding of combinatorial
integrin function in the epidermis. In this study, we generated mice with
epidermis-specific deletion of alpha3beta1, alpha9beta1, or both integrins as
well as keratinocyte lines expressing these integrin combinations. Consistent
with proangiogenic roles for alpha3beta1, alpha3-null keratinocytes showed
reduced paracrine stimulation of endothelial cell migration and survival, and
wounds of epidermis-specific alpha3 knockout mice displayed impaired
angiogenesis. Interestingly, alpha9beta1 in keratinocytes suppressed alpha3beta1
mediated stimulation of endothelial cells, and wounds of epidermis-specific
alpha9 knockout mice displayed delayed vascular normalization and reduced
endothelial apoptosis, indicating that alpha9beta1 cross-suppresses alpha3beta1
proangiogenic functions. Moreover, alpha9beta1 inhibited alpha3beta1 signaling
downstream of focal adhesion kinase (FAK) autoactivation at the point of Src
mediated phosphorylation of FAK Y861/Y925. Finally, alpha9beta1 cross-suppressed
many alpha3beta1-dependent genes, including the gene that encodes MMP-9, which we
implicated as a regulator of integrin-dependent cross talk to endothelial cells.
Our findings identify a novel physiological context for combinatorial integrin
signaling, laying the foundation for therapeutic strategies that manipulate
alpha9beta1 and/or alpha3beta1 during wound healing.
PMID- 28416481
TI - Western Diet Deregulates Bile Acid Homeostasis, Cell Proliferation, and
Tumorigenesis in Colon.
AB - Western-style diets (WD) high in fat and scarce in fiber and vitamin D increase
risks of colorectal cancer. Here, we performed a long-term diet study in mice to
follow tumorigenesis and characterize structural and metabolic changes in colon
mucosa associated with WD and predisposition to colorectal cancer. WD increased
colon tumor numbers, and mucosa proteomic analysis indicated severe deregulation
of intracellular bile acid (BA) homeostasis and activation of cell proliferation.
WD also increased crypt depth and colon cell proliferation. Despite increased
luminal BA, colonocytes from WD-fed mice exhibited decreased expression of the BA
transporters FABP6, OSTbeta, and ASBT and decreased concentrations of secondary
BA deoxycholic acid and lithocholic acid, indicating reduced activity of the
nuclear BA receptor FXR. Overall, our results suggest that WD increases cancer
risk by FXR inactivation, leading to BA deregulation and increased colon cell
proliferation. Cancer Res; 77(12); 3352-63. (c)2017 AACR.
PMID- 28416482
TI - NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer
Stem-like Cells in Human Non-Small Cell Lung Cancer.
AB - Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis,
relapse, and therapeutic resistance, but their specific pathogenic characters in
many cancers, including non-small cell lung cancer (NSCLC), have yet to be well
defined. Here, we develop findings that the growth factor HGF promotes CSC sphere
formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD
SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC).
In particular, we isolated a subpopulation of CD166+CD49fhiCD104-Lin- LCSC
present in all human specimens of NSCLC examined, regardless of their histologic
subtypes or genetic driver mutations. This specific cell population was
tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro
and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations
established that NOTCH1 was preferentially expressed in this cell subpopulation
and required for self-renewal via the transcription factor HES1. Through a
distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin
induced cell death. Notably, treatment with a gamma-secretase inhibitor that
blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum
sensitivity in vitro and in vivo Overall, our results define the pathogenic
characters of a cancer stem-like subpopulation in lung cancer, the targeting of
which may relieve platinum resistance in this disease. Cancer Res; 77(11); 3082
91. (c)2017 AACR.
PMID- 28416483
TI - SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug
Resistant Models of EGFR-Mutant Lung Cancer.
AB - Mutant-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are
active agents for the treatment of EGFR-mutant lung cancer. Specifically, these
agents can overcome the effects of the T790M mutation, which mediates resistance
to first- and second-generation EGFR TKI, and recent clinical trials have
documented their efficacy in patients with EGFR-mutant lung cancer. Despite
promising results, therapeutic efficacy is limited by the development of acquired
resistance. Here we report that Src family kinases (SFK) and focal adhesion
kinase (FAK) sustain AKT and MAPK pathway signaling under continuous EGFR
inhibition in osimertinib-sensitive cells. Inhibiting either the MAPK pathway or
the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition
exhibited the most potent effects on growth inhibition, induction of apoptosis,
and delay of acquired resistance. SFK family member YES1 was amplified in
osimertinib-resistant EGFR-mutant tumor cells, the effects of which were overcome
by combined treatment with osimertinib and SFK inhibitors. In conclusion, our
data suggest that the concomitant inhibition of both SFK/FAK and EGFR may be a
promising therapeutic strategy for EGFR-mutant lung cancer. Cancer Res; 77(11);
2990-3000. (c)2017 AACR.
PMID- 28416484
TI - SSRP1 Cooperates with PARP and XRCC1 to Facilitate Single-Strand DNA Break Repair
by Chromatin Priming.
AB - DNA single-strand breaks (SSB) are the most common form of DNA damage, requiring
repair processes that to initiate must overcome chromatin barriers. The FACT
complex comprised of the SSRP1 and SPT16 proteins is important for maintaining
chromatin integrity, with SSRP1 acting as an histone H2A/H2B chaperone in
chromatin disassembly during DNA transcription, replication, and repair. In this
study, we show that SSRP1, but not SPT16, is critical for cell survival after
ionizing radiation or methyl methanesulfonate-induced single-strand DNA damage.
SSRP1 is recruited to SSB in a PARP-dependent manner and retained at DNA damage
sites by N-terminal interactions with the DNA repair protein XRCC1. Mutational
analyses showed how SSRP1 function is essential for chromatin decondensation and
histone H2B exchange at sites of DNA strand breaks, which are both critical to
prime chromatin for efficient SSB repair and cell survival. By establishing how
SSRP1 facilitates SSB repair, our findings provide a mechanistic rationale to
target SSRP1 as a general approach to selectively attack cancer cells. Cancer
Res; 77(10); 2674-85. (c)2017 AACR.
PMID- 28416486
TI - A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer.
AB - Nanotechnology offers many possibilities to improve drug treatments, including
with regard to drug pharmacology. The current study reports a simple approach to
improve cisplatin efficacy in the treatment of colon cancer through the creation
of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ
CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells
and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited
at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin,
reflecting an enhancement in intracellular accumulation and DNA platination.
Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production,
expression of heavy metal-inducible and stress-inducible genes, stress kinase
cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis,
oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and
azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue
toxicity. Our results offer preclinical validation of a nanocarrier formulation
that can safely improve chemotherapeutic efficacy, address risks of drug
resistance, and improve patient compliance by enabling oral administration.
Cancer Res; 77(11); 2964-75. (c)2017 AACR.
PMID- 28416485
TI - Targeting Autocrine CCL5-CCR5 Axis Reprograms Immunosuppressive Myeloid Cells and
Reinvigorates Antitumor Immunity.
AB - The tumor-promoting potential of CCL5 has been proposed but remains poorly
understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major
regulator of immunosuppressive myeloid cells (IMC) of both monocytic and
granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation
of granulocytic myeloid-derived suppressor cells and tumor-associated
macrophages. In parallel, enhanced maturation of intratumoral neutrophils and
macrophages occurred in spite of tumor-derived CCL5. The refractory nature of
ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their
persistent lack of membrane-bound CCR5. The changes in the ccl5-null myeloid
compartment subsequently resulted in increased tumor-infiltrating cytotoxic CD8+
T cells and decreased regulatory T cells in tumor-draining lymph nodes. An
analysis of human triple-negative breast cancer specimens demonstrated an inverse
correlation between "immune CCR5" levels and the maturation status of tumor
infiltrating neutrophils as well as 5-year-survival rates. Targeting the host
CCL5 in bone marrow via nanoparticle-delivered expression silencing, in
combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of
IMC and robust antitumor immunities. Our study suggests that the myeloid CCL5
CCR5 axis is an excellent target for cancer immunotherapy. Cancer Res; 77(11);
2857-68. (c)2017 AACR.
PMID- 28416487
TI - Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer
Aggressiveness by Ambient Ionization Mass Spectrometry Imaging.
AB - Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among
gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous
borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and
have relatively indolent clinical behavior. The underlying biological differences
between HGSC and BOT call for accurate diagnostic methodologies and tailored
treatment options, and identification of molecular markers of aggressiveness
could provide valuable biochemical insights and improve disease management. Here,
we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image
and chemically characterize the metabolic profiles of HGSC, BOT, and normal
ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine
papillary branches in serous BOT and allowed for characterization of spatial
features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC.
Predictive markers of cancer aggressiveness were identified, including various
free fatty acids, metabolites, and complex lipids such as ceramides,
glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification
models built from a total of 89,826 individual pixels, acquired in positive and
negative ion modes from 78 different tissue samples, enabled diagnosis and
prediction of HGSC and all tumor samples in comparison with normal tissues, with
overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination
was achieved with an overall accuracy of 93.0%. Interestingly, our classification
model allowed identification of three BOT samples presenting unusual histologic
features that could be associated with the development of low-grade carcinomas.
Our results suggest DESI-MS as a powerful approach for rapid serous ovarian
cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903
13. (c)2017 AACR.
PMID- 28416488
TI - Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor
Initiating Cells.
AB - Oncogenic signaling by NOTCH is elevated in brain tumor-initiating cells (BTIC)
in malignant glioma, but the mechanism of its activation is unknown. Here we
provide evidence that tenascin-C (TNC), an extracellular matrix protein prominent
in malignant glioma, increases NOTCH activity in BTIC to promote their growth. We
demonstrate the proximal localization of TNC and BTIC in human glioblastoma
specimens and in orthotopic murine xenografts of human BTIC implanted
intracranially. In tissue culture, TNC was superior amongst several extracellular
matrix proteins in enhancing the sphere-forming capacity of glioma patient
derived BTIC. Exogenously applied or autocrine TNC increased BTIC growth through
an alpha2beta1 integrin-mediated mechanism that elevated NOTCH ligand Jagged1
(JAG1). Microarray analyses and confirmatory PCR and Western analyses in BTIC
determined that NOTCH signaling components including JAG1, ADAMTS15, and NICD1/2
were elevated in BITC after TNC exposure. Inhibition of gamma-secretase and
metalloproteinase proteolysis in the NOTCH pathway, or silencing of alpha2beta1
integrin or JAG1, reduced the proliferative effect of TNC on BTIC. Collectively,
our findings identified TNC as a pivotal initiator of elevated NOTCH signaling in
BTIC and define the establishment of a TN-alpha2beta1-JAG1-NOTCH signaling axis
as a candidate therapeutic target in glioma patients. Cancer Res; 77(12); 3231
43. (c)2017 AACR.
PMID- 28416489
TI - NRF2 Induction Supporting Breast Cancer Cell Survival Is Enabled by Oxidative
Stress-Induced DPP3-KEAP1 Interaction.
AB - NRF2 is a transcription factor serving as a master regulator of the expression of
many genes involved in cellular responses to oxidative and other stresses. In the
absence of stress, NRF2 is constantly synthesized but maintained at low levels as
it is targeted by KEAP1 for ubiquitination and proteasome-mediated degradation.
NRF2 binds KEAP1 mainly through a conserved "ETGE" motif that has also been found
in several other proteins, such as DPP3, which has been shown to bind KEAP1 and
enhance NRF2 function upon overexpression. Here we demonstrate the interaction
between endogenous DPP3 and endogenous KEAP1. We further show that the DPP3-KEAP1
interaction is strongly induced by hydrogen peroxide and that DPP3 is required
for timely NRF2 induction and nuclear accumulation in the estrogen receptor (ER)
positive MCF7 breast cancer cells. Moreover, we present evidence that the binding
of DPP3 to KEAP1 stabilizes the latter. Finally, we show that DPP3 is
overexpressed in breast cancer and that elevated levels of DPP3 mRNA correlate
with increased NRF2 downstream gene expression and poor prognosis, particularly
for ER-positive breast cancer. Our studies reveal novel insights into the
regulation of NRF2 and identify DPP3 and an NRF2 transcriptional signature as
potential biomarkers for breast cancer prognosis and treatment. Cancer Res;
77(11); 2881-92. (c)2017 AACR.
PMID- 28416490
TI - Preclinical Characterization of BET Family Bromodomain Inhibitor ABBV-075
Suggests Combination Therapeutic Strategies.
AB - ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently
entered phase I clinical trials. Comprehensive preclinical characterization of
ABBV-075 demonstrated broad activity across cell lines and tumor models,
representing a variety of hematologic malignancies and solid tumor indications.
In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent
G1 cell-cycle arrest without extensive apoptosis. In this study, we show that
ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non
Hodgkin lymphoma, and multiple myeloma cells. Apoptosis induced by ABBV-075 was
mediated in part by modulation of the intrinsic apoptotic pathway, exhibiting
synergy with the BCL-2 inhibitor venetoclax in preclinical models of AML. In
germinal center diffuse large B-cell lymphoma, BCL-2 levels or venetoclax
sensitivity predicted the apoptotic response to ABBV-075 treatment. In vivo
combination studies uncovered surprising benefits of low doses of ABBV-075
coupled with bortezomib and azacitidine treatment, despite the lack of in vitro
synergy between ABBV-075 and these agents. The in vitro/in vivo activities of
ABBV-075 described here may serve as a useful reference to guide the development
of ABBV-075 and other BET family inhibitors for cancer therapy. Cancer Res;
77(11); 2976-89. (c)2017 AACR.
PMID- 28416491
TI - Locoregional Effects of Microbiota in a Preclinical Model of Colon
Carcinogenesis.
AB - Inflammation and microbiota are critical components of intestinal tumorigenesis.
To dissect how the microbiota contributes to tumor distribution, we generated
germ-free (GF) ApcMin/+ and ApcMin/+ ;Il10-/- mice and exposed them to specific
pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon
tumorigenesis significantly correlated with inflammation in SPF-housed ApcMin/+
;Il10-/- , but not in ApcMin/+ mice. In contrast, small intestinal neoplasia
development significantly correlated with age in both ApcMin/+ ;Il10-/- and
ApcMin/+ mice. GF ApcMin/+ ;Il10-/- mice conventionalized by an SPF microbiota
had significantly more colon tumors compared with GF mice. Gnotobiotic studies
revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2
adhesins failed to induce inflammation and tumorigenesis, pks+Escherichia coli
promoted tumorigenesis in the ApcMin/+ ;Il10-/- model in a colibactin-dependent
manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest
a distinct etiology of cancers in different locations of the gut, where colon
cancer is primarily driven by inflammation and the microbiome, while age is a
driving force for small intestine cancer. Cancer Res; 77(10); 2620-32. (c)2017
AACR.
PMID- 28416492
TI - Intravitreal triamcinolone acetate for radiation maculopathy recalcitrant to high
dose intravitreal bevacizumab.
AB - BACKGROUND/AIMS: To evaluate the effect of adjuvant intravitreal triamcinolone
acetonide (ITA) for radiation maculopathy (RM) recalcitrant to high-dose
bevacizumab in patients with choroidal melanoma after plaque radiotherapy.
METHODS: Eight eyes of eight patients with RM secondary to plaque radiotherapy
for choroidal melanoma, recalcitrant to high-dose bevacizumab (3.0 mg) were
retrospectively evaluated. Intravitreal injections of ITA (4 mg/0.1 mL) were
performed at 4-week to 16-week intervals as an adjunct to continued bevacizumab
therapy. Change in central foveal thickness (CFT) as measured by optical
coherence tomography and change in visual acuity (VA) were the main outcome
measures. RESULTS: At the time of diagnosis of choroidal melanoma, VA was 20/20
to 20/50 in 88% (n=7) and 20/60 to 20/200 in 12% (n=1). The mean radiation dose
to the fovea was 81 Gy (median 75.2 Gy; range: 22.72-132.8 Gy). The mean onset to
RM was 25 months after plaque therapy (median 25 months; range 12-44 months). At
the time of initiation of ITA, VA was 20/20 to 20/50 in 38% (3/8), and 20/60 to
20/200 in 62% (5/8). After initiation of ITA, VA was stable or improved in 100%
of patients (n=8) at 3 months, 88% at 6 months, 88% at 9 months and 75% at 12
months. Mean CFT was 417 um at ITA initiation, 339 um at 1 month, 355 um at 6
months, 339 um at 9 months and 359 um at 1 year. CONCLUSION: Intravitreal
triamcinolone can be added to preserve vision and decrease macular oedema in
patients with RM recalcitrant to high-dose anti-vascular endothelial growth
factor agents.
PMID- 28416493
TI - Phacoemulsification compared with phacotrabeculectomy surgery: a within-person
observational cohort study.
AB - AIM: To compare reduction in intraocular pressure (IOP) and gain in visual acuity
(VA) following phacotrabeculectomy (PT) and phacoemulsification(phaco) in
Tanzanian patients with primary open angle glaucoma(POAG). SETTING: CCBRT
Hospital, Dar es Salaam, Tanzania. DESIGN: Within-person observational cohort
study. METHODS: Within each patient, one eye had PT and the other phaco. Patients
were followed for up to 5-1/2 years, and IOP and VA in each eye were assessed.
For a small group of patients, two additional postoperative time points were
compared. RESULTS: 52 patients (34 male) with a mean age of 70 years (SD 8 years)
were enrolled in the study. For those with 250 days or more follow-up, both
operations resulted in lower IOPs and improved VA (p<0.001). The average drop in
IOP was 50% (95%CI 45% to 55%) for PT and 41% (95% CI 36% to 46%) for phaco. Mean
IOP was lower in the PT group 12.9 mm Hg vs 16.8 mm Hg (p=0.004). Extended follow
up in nine patients showed a rise in IOP of 1.8 mm Hg for PT and 4.2 mm Hg for
phaco eyes between first (mean, 337 days) and second (mean 1482 days) follow-up
(p=0.18). CONCLUSION: In this small study in African patients, PT resulted in
lower IOPs than phacoemulsification alone but the difference between the
procedures was relatively small. Phacoemulsification alone was effective in
reducing IOP and improving VA for several years in this population. Given the
relative simplicity of phacoemulsification, it is a therapeutic option worthy of
consideration in some settings.
PMID- 28416494
TI - Long-term clinical course of normotensive preperimetric glaucoma.
AB - AIMS: To evaluate the long-term clinical course of normotensive preperimetric
glaucoma (PPG). METHODS: We retrospectively analysed 130 eyes of 130 patients
initially diagnosed as having preperimetric normal tension glaucoma and followed
these cases for at least 5 years with reliable visual field (VF) examinations by
standard automated perimetry. When the VF defect (VFD) met Anderson-Patella's
criteria on three or more consecutive examinations, and consistently met the
criteria on subsequent examinations, we concluded that a glaucomatous VFD was
present. Predictive factors for developing a VFD were assessed. RESULTS: Seventy
one eyes (54.6%) developed a glaucomatous VFD during the follow-up period. The
mean deviation slope varied from -0.90 to 0.41 dB/year. A Cox proportional hazard
model showed that having a greater initial pattern SD (p=0.005), the presence of
optic disc haemorrhage (p=0.022) and higher mean intraocular pressure (IOP) prior
to developing a VFD (p=0.039) were related to developing a VFD. CONCLUSIONS: Our
findings confirmed that the mean IOP, but not the IOP fluctuation, is strongly
associated with the development of a VFD in cases of PPG.
PMID- 28416495
TI - Ultrastructural study of peripheral and central stroma of keratoconus cornea.
AB - PURPOSE: Assess the lamellar organisation of the peripheral and central stroma of
the keratoconus (KC) and normal cornea. METHODS: Five normal and three KC corneas
were fixed in 2.5% glutaraldehyde and processed for electron microscopy. The
ultrathin sections were observed under JEOL 1400 TEM, and digital images were
taken with a bottom-mounted 11-megapixel Quamisa camera, using the iTEM software.
Measurements of the lamellae were carried out using the iTEM software.
Statistical analysis was performed using the SPSS software. RESULTS: The lamellar
organisation at the centre and periphery of the KC cornea was disrupted by the
presence of multiple undulations, which were more aggressive at the posterior
stroma. Among the KC cornea, the mean lamellar thickness of the peripheral middle
(1030.32+/-86.25 nm) and posterior (615.68+/-30.94 nm) stroma was also
significantly (p<0.05) thinner than their corresponding areas of the central KC
cornea (1151.1+/-48 nm; 783.57+/-31.10 nm). At the periphery of KC cornea, just
above the Descemet's membrane (DM), small undulations appeared to emerge out from
the DM. Furthermore, the anterior stroma of the peripheral cornea contained
several lamellar sutures. The mean lamellar thickness of the peripheral and
central KC cornea was significantly (p<0.0001) thinner than the corresponding
areas of the normal cornea. CONCLUSION: The present study reveals the involvement
of lamellae in the peripheral stroma in the pathogenicity of the KC cornea. The
emergence of small undulations in the DM suggests that the formation of
undulation might be starting from the DM.
PMID- 28416496
TI - Long-term cost reduction of routine medications following a residential programme
combining physical activity and nutrition in the treatment of type 2 diabetes: a
prospective cohort study.
AB - OBJECTIVES: To demonstrate that lifestyle modifications will reduce the cost of
routine medications in individuals with type 2 diabetes (T2D), through a
mechanism involving glycaemic control. DESIGN: A within-trial cost-medication
analysis with a 1-year time horizon. SETTING: Controlled environment within the
spa resort of Chatel-Guyon, France. PARTICIPANTS: Twenty-nine participants (aged
50-70 years) with T2D. INTERVENTIONS: A 1-year follow-up intervention, beginning
with a 3-week residential programme combining high exercise volume (15-20
hours/week), restrictive diet (-500 kcal/day) and education. Participants
continued their routine medication, independently managed by their general
practitioner. MAIN OUTCOME MEASURES: Number of medications, number of pills, cost
of medications and health-related outcomes. RESULTS: Twenty-six participants
completed the 1-year intervention. At 1 year, 14 patients out of 26 (54%)
stopped/decreased their medications whereas only 5 (19%) increased or introduced
new drugs (chi2=6.3, p=0.02). The number of pills per day decreased by 1.3+/-0.3
at 12 months (p<0.001). The annual cost of medications for T2D were lower at 1
year (?135.1+/-43.9) versus baseline (?212.6+/-35.8) (p=0.03). The regression
coefficients on costs of routine medication were 0.507 (95% CI 0.056 to 0.959,
p=0.027) for HbA1c and 0.156 (95% CI -0.010 to 0.322, p=0.06) for blood glucose
levels. Diabetics patients with HbA1c >6.5% in the highest (last) quartile
doubled their routine medication costs (66% vs 33%, p=0.037). CONCLUSIONS:
Individuals with T2D reduced routine medication costs following a long-term
lifestyle intervention that started with a 3-week residential programme.
Combining high exercise volume, restrictive diet and education effectively
supported the health of T2D. The main factor explaining reduced medication costs
was better glycaemic control, independent of weight changes. Despite limitations
precluding generalisability, cost-effective results of reduced medication should
contribute to the evidence base required to promote lifestyle interventions for
individuals with T2D. TRIAL REGISTRATION NUMBER: NCT00917917; Post-results.
PMID- 28416497
TI - Prognostication in critically ill patients with severe traumatic brain injury:
the TBI-Prognosis multicentre feasibility study.
AB - OBJECTIVE: Severe traumatic brain injury is a significant cause of morbidity and
mortality in young adults. Assessing long-term neurological outcome after such
injury is difficult and often characterised by uncertainty. The objective of this
feasibility study was to establish the feasibility of conducting a large,
multicentre prospective study to develop a prognostic model of long-term
neurological outcome in critically ill patients with severe traumatic brain
injury. DESIGN: A prospective cohort study. SETTING: 9 Canadian intensive care
units enrolled patients suffering from acute severe traumatic brain injury.
Clinical, biological, radiological and electrophysiological data were
systematically collected during the first week in the intensive care unit.
Mortality and functional outcome (Glasgow Outcome Scale extended) were assessed
on hospital discharge, and then 3, 6 and 12 months following injury. OUTCOMES:
The compliance to protocolised test procedures was the primary outcome. Secondary
outcomes were enrolment rate and compliance to follow-up. RESULTS: We
successfully enrolled 50 patients over a 12-month period. Most patients were male
(80%), with a median age of 45 years (IQR 29.0-60.0), a median Injury Severity
Score of 38 (IQR 25-50) and a Glasgow Coma Scale of 6 (IQR 3-7). Mortality was
38% (19/50) and most deaths occurred following a decision to withdraw life
sustaining therapies (18/19). The main reasons for non-enrolment were the time
window for inclusion being after regular working hours (35%, n=23) and oversight
(24%, n=16). Compliance with protocolised test procedures ranged from 92% to 100%
and enrolment rate was 43%. No patients were lost to follow-up at 6 months and 2
were at 12 months. CONCLUSIONS: In this multicentre prospective feasibility
study, we achieved feasibility objectives pertaining to compliance to test,
enrolment and follow-up. We conclude that the TBI-Prognosis prospective
multicentre study in severe traumatic brain injury patients in Canada is
feasible.
PMID- 28416498
TI - Deprescribing anticholinergic and sedative medicines: protocol for a Feasibility
Trial (DEFEAT-polypharmacy) in residential aged care facilities.
AB - INTRODUCTION: Targeted deprescribing of anticholinergic and sedative medicines
can lead to positive health outcomes in older people; as they have been
associated with cognitive and physical functioning decline. This study will
examine whether the proposed intervention is feasible at reducing the
prescription of anticholinergic and sedative medicines in older people. METHODS
AND ANALYSIS: The Standard Protocol Items: Recommendations for Interventional
trials (SPIRIT checklist) was used to develop and report the protocol. Single
group (precomparison and postcomparison) feasibility study design. STUDY
POPULATION: 3 residential care homes have been recruited. INTERVENTION: This will
involve a New Zealand registered pharmacist using peer-reviewed deprescribing
guidelines, to recommend to general practitioners (GPs), sedative and
anticholinergic medicines that can be deprescribed. The cumulative use of
anticholinergic and sedative medicines for each participant will be quantified,
using the Drug Burden Index (DBI). OUTCOMES: The primary outcome will be the
change in the participants' DBI total and DBI PRN 3 and 6 months after
implementing the deprescribing intervention. Secondary outcomes will include the
number of recommendations taken up by the GP, participants' cognitive
functioning, depression, quality of life, activities of daily living and number
of falls. DATA COLLECTION POINTS: Participants' demographic and clinical data
will be collected at the time of enrolment, along with the DBI. Outcome measures
will be collected at the time of enrolment, 3 and 6 months' postenrolment. ETHICS
AND DISSEMINATION: Ethics approval has been granted by the Human Disability and
Ethics Committee. Ethical approval number (16/NTA/61). TRIAL REGISTRATION NUMBER:
Pre-results; ACTRN12616000721404.
PMID- 28416499
TI - Has the role of personal income in alcohol drinking among teenagers changed
between 1983 and 2013: a series of nationally representative surveys in Finland.
AB - OBJECTIVE: Affordability is known to be a key determinant of alcohol consumption,
possibly even more important in adolescence. Relating adolescent drinking pattern
developments over a period of time to trends in adolescent income can yield
information on the significance of parental control of adolescent income. DESIGN:
Biannual repeated cross-sectional surveys. SETTING: Nationally representative
samples. PARTICIPANTS: 14-year-old adolescents in the period 1983-2013 in Finland
(N=33 771). RESULTS: Adolescents' alcohol drinking pattern was significantly
associated with their disposable income. The OR for monthly drunkenness versus
abstinence was 6.6 (95% CI 5.0 to 8.8) among girls and 9.0 (6.3 to 13.0) among
boys in the highest income group compared with the lowest. However, the
association between income and drinking pattern weakened considerably during the
30-year period. CONCLUSIONS: Disposable income has been a significant predictor
of adolescent alcohol drinking in the past 30 years. However, in the recent
years, the amount of disposable money has decreased in importance.
PMID- 28416500
TI - Cluster randomised controlled trial of a consumer behaviour intervention to
improve healthy food purchases from online canteens: study protocol.
AB - INTRODUCTION: School canteens represent an opportune setting in which to deliver
public health nutrition strategies given their wide reach, and frequent use by
children. Online school canteen ordering systems, where students order and pay
for their lunch online, provide an avenue to improve healthy canteen purchases
through the application of consumer behaviour strategies that impact on
purchasing decisions. The aim of this study is to assess the efficacy of a
consumer behaviour intervention implemented in an online school canteen ordering
system in reducing the kilojoule, saturated fat, sugar and sodium content of
primary student lunch orders. METHODS AND ANALYSIS: The study will employ a
cluster randomised controlled trial design. Approximately 1040 students (aged 5
12 years) from 10 primary schools in New South Wales, Australia, currently using
an online canteen ordering system will be invited to participate. Schools will be
randomised in a 1:1 ratio to receive either the intervention (enhanced system) or
control (standard online ordering only). The intervention will include evidence
based strategies shown to influence healthy food purchasing (strategies targeting
availability, menu labelling, placement and prompting). The primary outcomes of
the trial will be the mean content per student online lunch order of (1) energy
(kJ), (2) saturated fat (g), (3) sugar (g) and (4) sodium (mg). The impact of the
intervention will be determined by between-group assessment of the nutritional
content of lunch purchases over a 2-month period postintervention initiation.
ETHICS AND DISSEMINATION: The study was approved by the Hunter New England Human
Research Ethics Committee, University of Newcastle Human Research Ethics
Committee and New South Wales Department of Education and School Communities.
Study findings will be disseminated widely through peer-reviewed publications and
relevant presentations in international conferences and to stakeholders. TRIAL
REGISTRATION NUMBER: ACTRN12616000499482.
PMID- 28416502
TI - Interim PET-driven strategy in de novo diffuse large B-cell lymphoma: do we trust
the driver?
AB - 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) has become a
central tool for both accurate initial staging and determination of prognosis
after treatment of diffuse large B-cell lymphoma (DLBCL). However, the role of
PET during treatment (iPET) in daily practice remains a matter of significant
debate. This perspective reviews the published studies on iPET in DLBCL,
including the methods used to analyze iPET, its timing, and studies of iPET
driven therapy to illuminate where daily practice may benefit from the use of
iPET. When performed after 2 and/or 4 courses of immunochemotherapy, iPET has a
very good negative predictive value, utilizing both visual (qualitative) and
semiquantitative methods. The visual method accurately predicts outcome for
patients with limited disease. The semiquantitative method, eg, the change of the
difference of maximum standardized uptake value (DeltaSUVmax), is for patients
with advanced DLBCL, for whom iPET identifies patients with very good outcome
with continuation of standard therapy. A low DeltaSUVmax also helps identify
patients with a risk for relapse averaging 50% and warrants review of their
scheduled therapy. To date, no trial has demonstrated the superiority of an iPET
driven strategy in DLBCL. However, the very good negative and good positive
predictive values of iPET support its use in daily practice as a better
predictive tool than contrast-enhanced computed tomographic scan for therapeutic
decision making.
PMID- 28416501
TI - Protocol for a placebo-controlled, within-participants crossover trial evaluating
the efficacy of intranasal oxytocin to improve pain and function among women with
chronic pelvic musculoskeletal pain.
AB - INTRODUCTION: This protocol presents the rationale and design for a trial
evaluating the efficacy of intranasal oxytocin in improving pain and function
among women with chronic pelvic musculoskeletal pain. Oxytocin is a neuropeptide
traditionally recognised for involvement in labour, delivery and lactation. Novel
evidence suggests that oxytocin decreases pain sensitivity in humans. While
oxytocin administration has been reported to lower pain sensitivity among
patients experiencing chronic back pain, headache, constipation and colon pain,
no research has evaluated the association between intranasal oxytocin and chronic
pelvic musculoskeletal pain. The association between oxytocin and pain may differ
in women with chronic pelvic musculoskeletal pain relative to other chronic pain
conditions because of the abundance of oxytocin receptors in the uterus. METHODS
AND ANALYSIS: This is a prospective, randomised, placebo-controlled, double
blind, within-participants crossover trial. 50 women with chronic pelvic
musculoskeletal pain will be recruited through a local chronic pain centre and
gynaecology clinics. Women will complete baseline measures and be randomised to
an experimental or control condition that involve 2 weeks of self-administering
twice-daily doses of 24 IU intranasal oxytocin or placebo, respectively. Women
will then undergo a 2-week washout period before crossing over to receive the
condition that they had not yet received. The primary outcome will be pain and
function measured using the Brief Pain Inventory-Short Form. Secondary outcomes
include emotional function, sleep disturbance and global impression of change.
This trial will provide data on the 14-day safety and side-effect profile of
intranasal oxytocin self-administered as an adjuvant treatment for chronic pelvic
musculoskeletal pain. ETHICS AND DISSEMINATION: This trial was granted approval
from Health Canada and the University of Calgary Conjoint Health Research Ethics
Board, and is registered online at ClinicalTrials.gov (#NCT02888574). Results
will be disseminated to healthcare professionals through peer-reviewed
publications and to the general public through press releases. TRIAL REGISTRATION
NUMBER: NCT02888574; Pre-results.
PMID- 28416503
TI - Invariant natural killer T cells ameliorate murine chronic GVHD by expanding
donor regulatory T cells.
AB - Chronic graft-versus-host-disease (cGVHD) can cause multiorgan system disease,
typically with autoimmune-like features, resulting in high mortality and
morbidity caused by treatment limitations. Invariant natural killer T cells
(iNKTs), a small population characterized by expression of a semi-invariant T
cell receptor, rapidly produce copious amounts of diverse cytokines on activation
that exert potent immune regulatory function. Here, we show that iNKTs are
significantly reduced in a cGVHD murine model that recapitulates several aspects
of autoimmunity and organ fibrosis observed in patients with cGVHD. Low iNKT
infused doses effectively prevented and, importantly, reversed established cGVHD,
as did third-party iNKTs. iNKTs suppressed the autoimmune response by reducing
the germinal center (GC) reaction, which was associated with an increase in total
Tregs and follicular Tregs (Tfr) that control the GC reaction, along with
pathogenic antibody production. Treg depletion during iNKT infusions completely
abolished iNKT efficacy in treating cGVHD. iNKT cell interleukin 4 production and
GC migration were critical to cGVHD reversal. In vivo stimulation of iNKT cells
by alpha-galactosyl-ceramide was effective in both preventing and treating cGVHD.
Together, this study demonstrates iNKT deficiency in cGVHD mice and highlights
the key role of iNKTs in regulating cGVHD pathogenesis and as a potentially novel
prophylactic and therapeutic option for patients with cGVHD.
PMID- 28416504
TI - Introduction to a series of reviews on clinical platelet disorders.
PMID- 28416505
TI - Hematopoietic transcription factor mutations: important players in inherited
platelet defects.
AB - Transcription factors (TFs) are proteins that bind to specific DNA sequences and
regulate expression of genes. The molecular and genetic mechanisms in most
patients with inherited platelet defects are unknown. There is now increasing
evidence that mutations in hematopoietic TFs are an important underlying cause
for defects in platelet production, morphology, and function. The hematopoietic
TFs implicated in patients with impaired platelet function and number include
runt-related transcription factor 1, Fli-1 proto-oncogene, E-twenty-six (ETS)
transcription factor (friend leukemia integration 1), GATA-binding protein 1,
growth factor independent 1B transcriptional repressor, ETS variant 6, ecotropic
viral integration site 1, and homeobox A11. These TFs act in a combinatorial
manner to bind sequence-specific DNA within promoter regions to regulate lineage
specific gene expression, either as activators or repressors. TF mutations induce
rippling downstream effects by simultaneously altering the expression of multiple
genes. Mutations involving these TFs affect diverse aspects of megakaryocyte
biology, and platelet production and function, culminating in thrombocytopenia
and platelet dysfunction. Some are associated with predisposition to hematologic
malignancies. These TF variants may occur more frequently in patients with
inherited platelet defects than generally appreciated. This review focuses on
alterations in hematopoietic TFs in the pathobiology of inherited platelet
defects.
PMID- 28416506
TI - Clinical updates in adult immune thrombocytopenia.
AB - Immune thrombocytopenia (ITP) occurs in 2 to 4/100 000 adults and results in
variable bleeding symptoms and thrombocytopenia. In the last decade, changes in
our understanding of the pathophysiology of the disorder have led to the
publication of new guidelines for the diagnosis and management of ITP and
standards for terminology. Current evidence supports alternatives to splenectomy
for second-line management of patients with persistently low platelet counts and
bleeding. Long-term follow-up data suggest both efficacy and safety, in
particular, for the thrombopoietin receptor agonists and the occurrence of late
remissions. Follow-up of patients who have undergone splenectomy for ITP reveals
significant potential risks that should be discussed with patients and may
influence clinician and patient choice of second-line therapy. Novel therapeutics
are in development to address ongoing treatment gaps.
PMID- 28416507
TI - Thrombotic thrombocytopenic purpura.
AB - Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening
thrombotic microangiopathy characterized by microangiopathic hemolytic anemia,
severe thrombocytopenia, and organ ischemia linked to disseminated microvascular
platelet rich-thrombi. TTP is specifically related to a severe deficiency in
ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats,
member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13
deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely,
it is inherited via mutations of the ADAMTS13 gene. The first acute episode of
TTP usually occurs during adulthood, with a predominant anti-ADAMTS13 autoimmune
etiology. In rare cases, however, TTP begins as soon as childhood, with frequent
inherited forms. TTP is ~2-fold more frequent in women, and its outcome is
characterized by a relapsing tendency. Rapid recognition of TTP is crucial to
initiate appropriate treatment. The first-line therapy for acute TTP is based on
daily therapeutic plasma exchange supplying deficient ADAMTS13, with or without
steroids. Additional immune modulators targeting ADAMTS13 autoantibodies are
mainly based on steroids and the humanized anti-CD20 monoclonal antibody
rituximab. In refractory or unresponsive TTP, more intensive therapies including
twice-daily plasma exchange; pulses of cyclophosphamide, vincristine, or
cyclosporine A; or salvage splenectomy are considered. New drugs including N
acetylcysteine, bortezomib, recombinant ADAMTS13, and caplacizumab show promise
in the management of TTP. Also, long-term follow-up of patients with TTP is
crucial to identify the occurrence of other autoimmune diseases, to control
relapses, and to evaluate psychophysical sequelae. Further development of both
patients' registries worldwide and innovative drugs is still needed to improve
TTP management.
PMID- 28416509
TI - None of the above: thrombotic microangiopathy beyond TTP and HUS.
AB - Acquired thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome
(HUS) are appropriately at the top of a clinician's differential when a patient
presents with a clinical picture consistent with an acute thrombotic
microangiopathy (TMA). However, there are several additional diagnoses that
should be considered in patients presenting with an acute TMA, especially in
patients with nondeficient ADAMTS13 (a disintegrin and metalloproteinase with a
thrombospondin type 1 motif, member 13) activity (>10%). An increased awareness
of drug-induced TMA is also essential because the key to their diagnosis more
often is an appropriately detailed medical history to inquire about potential
exposures. Widespread inflammation and endothelial damage are central in the
pathogenesis of the TMA, with the treatment directed at the underlying disease if
possible. TMA presentations in the critically ill, drug-induced TMA, cancer
associated TMA, and hematopoietic transplant-associated TMA (TA-TMA) and their
specific treatment, where applicable, will be discussed in this manuscript. A
complete assessment of all the potential etiologies for the TMA findings
including acquired TTP will allow for a more accurate diagnosis and prevent
prolonged or inappropriate treatment with plasma exchange therapy when it is less
likely to be successful.
PMID- 28416508
TI - HUS and atypical HUS.
AB - Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by
intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is
usually categorized as typical, caused by Shiga toxin-producing Escherichia coli
(STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled
complement activation, or as secondary HUS with a coexisting disease. In recent
years, a general understanding of the pathogenetic mechanisms driving HUS has
increased. Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with
STEC, whereas aHUS is associated primarily with mutations or autoantibodies
leading to dysregulated complement activation. Among the 30% to 50% of patients
with HUS who have no detectable complement defect, some have either impaired
diacylglycerol kinase epsilon (DGKepsilon) activity, cobalamin C deficiency, or
plasminogen deficiency. Some have secondary HUS with a coexisting disease or
trigger such as autoimmunity, transplantation, cancer, infection, certain
cytotoxic drugs, or pregnancy. The common pathogenetic features in STEC-HUS,
aHUS, and secondary HUS are simultaneous damage to endothelial cells,
intravascular hemolysis, and activation of platelets leading to a procoagulative
state, formation of microthrombi, and tissue damage. In this review, the
differences and similarities in the pathogenesis of STEC-HUS, aHUS, and secondary
HUS are discussed. Common for the pathogenesis seems to be the vicious cycle of
complement activation, endothelial cell damage, platelet activation, and
thrombosis. This process can be stopped by therapeutic complement inhibition in
most patients with aHUS, but usually not those with a DGKepsilon mutation, and
some patients with STEC-HUS or secondary HUS. Therefore, understanding the
pathogenesis of the different forms of HUS may prove helpful in clinical
practice.
PMID- 28416510
TI - Erythrocyte sialoglycoproteins engage Siglec-9 on neutrophils to suppress
activation.
AB - Healthy blood neutrophils are functionally quiescent in the bloodstream, have a
short lifespan, and exit the circulation to carry out innate immune functions, or
undergo rapid apoptosis and macrophage-mediated clearance to mitigate host tissue
damage. Limitation of unnecessary intravascular neutrophil activation is also
important to prevent serious inflammatory pathologies. Because neutrophils become
easily activated after purification, we carried out ex vivo comparisons with
neutrophils maintained in whole blood. We found a difference in activation state,
with purified neutrophils showing signs of increased reactivity: shedding of l
selectin, CD11b upregulation, increased oxidative burst, and faster progression
to apoptosis. We discovered that erythrocytes suppressed neutrophil activation ex
vivo and in vitro, including reduced l-selectin shedding, oxidative burst,
chemotaxis, neutrophil extracellular trap formation, bacterial killing, and
induction of apoptosis. Selective and specific modification of sialic acid side
chains on erythrocyte surfaces with mild sodium metaperiodate oxidation followed
by aldehyde quenching with 4-methyl-3-thiosemicarbazide reduced neutrophil
binding to erythrocytes and restored neutrophil activation. By enzyme-linked
immunosorbent assay and immunofluorescence, we found that glycophorin A, the most
abundant sialoglycoprotein on erythrocytes, engaged neutrophil Siglec-9, a sialic
acid-recognizing receptor known to dampen innate immune cell activation. These
studies demonstrate a previously unsuspected role for erythrocytes in suppressing
neutrophils ex vivo and in vitro and help explain why neutrophils become easily
activated after separation from whole blood. We propose that a sialic acid-based
"self-associated molecular pattern" on erythrocytes also helps maintain
neutrophil quiescence in the bloodstream. Our findings may be relevant to some
prior experimental and clinical studies of neutrophils.
PMID- 28416511
TI - Heparin-induced thrombocytopenia.
AB - Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin
therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin.
Pathogenic antibodies to PF4/heparin bind and activate cellular FcgammaRIIA on
platelets and monocytes to propagate a hypercoagulable state culminating in life
threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies
develop commonly after heparin exposure, but only a subset of sensitized patients
progress to life-threatening complications of thrombocytopenia and thrombosis.
Recent scientific developments have clarified mechanisms underlying PF4/heparin
immunogenicity, disease susceptibility, and clinical manifestations of disease.
Insights from clinical and laboratory findings have also been recently harnessed
for disease prevention. This review will summarize our current understanding of
HIT by reviewing pathogenesis, essential clinical and laboratory features, and
management.
PMID- 28416513
TI - What is broad-range 16S rDNA PCR?
PMID- 28416512
TI - Investigating the Genetic Architecture of the PR Interval Using Clinical
Phenotypes.
AB - BACKGROUND: One potential use for the PR interval is as a biomarker of disease
risk. We hypothesized that quantifying the shared genetic architectures of the PR
interval and a set of clinical phenotypes would identify genetic mechanisms
contributing to PR variability and identify diseases associated with a genetic
predictor of PR variability. METHODS AND RESULTS: We used ECG measurements from
the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63
genetically modulated diseases from the eMERGE network (Electronic Medical
Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG)
between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the
63 phenotypes. The PR segment was genetically correlated with atrial fibrillation
(rG=-0.88; P=0.0009). An analysis of metabolic phenotypes in ARIC also showed
that the P wave was genetically correlated with waist circumference (rG=0.47;
P=0.02). A genetically predicted PR interval phenotype based on 645 714 single
nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89
per SD change; 95% confidence interval, 0.83-0.95; P=0.0006). The differing
pattern of associations among the PR phenotypes is consistent with analyses that
show that the genetic correlation between the P wave and PR segment was not
significantly different from 0 (rG=-0.03 [0.16]). CONCLUSIONS: The genetic
architecture of the PR interval comprises modulators of atrial fibrillation risk
and obesity.
PMID- 28416514
TI - Optical Mapping Approaches on Muscleblind-Like Compound Knockout Mice for
Understanding Mechanistic Insights Into Ventricular Arrhythmias in Myotonic
Dystrophy.
AB - BACKGROUND: Cardiac arrhythmias are common causes of death in patients with
myotonic dystrophy (dystrophia myotonica [DM]). Evidence shows that atrial
tachyarrhythmia is an independent risk factor for sudden death; however, the
relationship is unclear. METHODS AND RESULTS: Control wild-type (Mbnl1+/+;
Mbnl2+/+ ) and DM mutant (Mbnl1-/-; Mbnl2+/- ) mice were generated by crossing
double heterozygous knockout (Mbnl1+/-; Mbnl2+/- ) mice. In vivo
electrophysiological study and optical mapping technique were performed to
investigate mechanisms of ventricular tachyarrhythmias. Transmission electron
microscopy scanning was performed for myocardium ultrastructural analysis. DM
mutant mice were more vulnerable to anesthesia medications and program electrical
pacing: 2 of 12 mice had sudden apnea and cardiac arrest during premedication of
general anesthesia; 9 of the remaining 10 had atrial tachycardia and/or
atrioventricular block, but none of the wild-type mice had spontaneous
arrhythmias; and 9 of 10 mice had pacing-induced ventricular tachyarrhythmias,
but only 1 of 14 of the wild-type mice. Optical mapping studies revealed
prolonged action potential duration, slower conduction velocity, and steeper
conduction velocity restitution curves in the DM mutant mice than in the wild
type group. Spatially discordant alternans was more easily inducible in DM mutant
than wild-type mice. Transmission electron microscopy showed disarranged
myofibrils with enlarged vacuole-occupying mitochondria in the DM mutant group.
CONCLUSIONS: This DM mutant mouse model presented with clinical myofibril
ultrastructural abnormality and cardiac arrhythmias, including atrial
tachyarrhythmias, atrioventricular block, and ventricular tachyarrhythmias.
Optical mapping studies revealed prolonged action potential duration and slow
conduction velocity in the DM mice, leading to vulnerability of spatially
discordant alternans and ventricular arrhythmia induction to pacing.
PMID- 28416515
TI - Multivariate modelling of faecal bacterial profiles of patients with IBS predicts
responsiveness to a diet low in FODMAPs.
AB - OBJECTIVE: The effects of dietary interventions on gut bacteria are ambiguous.
Following a previous intervention study, we aimed to determine how differing
diets impact gut bacteria and if bacterial profiles predict intervention
response. DESIGN: Sixty-seven patients with IBS were randomised to traditional
IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides
and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4
days during screening and intervention. Faecal samples and IBS Symptom Severity
Score (IBS-SSS) reports were collected before (baseline) and after intervention.
A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial
composition. Per protocol analysis was performed on 61 patients from whom
microbiome data were available. RESULTS: Responders (reduced IBS-SSS by >=50) to
low FODMAP, but not traditional, dietary intervention were discriminated from non
responders before and after intervention based on faecal bacterial profiles.
Bacterial abundance tended to be higher in non-responders to a low FODMAP diet
compared with responders before and after intervention. A low FODMAP intervention
was associated with an increase in Dysbiosis Index (DI) scores in 42% of
patients; while decreased DI scores were recorded in 33% of patients following a
traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional
IBS diet had higher DI scores than responders at baseline. Finally, while a
traditional IBS diet was not associated with significant reduction of
investigated bacteria, a low FODMAP diet was associated with reduced
Bifidobacterium and Actinobacteria in patients, correlating with lactose
consumption. CONCLUSIONS: A low FODMAP, but not a traditional IBS diet may have
significant impact on faecal bacteria. Responsiveness to a low FODMAP diet
intervention may be predicted by faecal bacterial profiles. TRIAL REGISTRATION
NUMBER: NCT02107625.
PMID- 28416517
TI - SUA levels should not be maintained <3 mg/dL for several years. Response to
'EULAR gout treatment guidelines by Richette et al: uric acid and neurocognition
by Singh et al'.
PMID- 28416518
TI - The influence of discrepant imaging judgements on the classification of axial
spondyloarthritis is limited: a replication in the SpondyloArthritis Caught Early
(SPACE) cohort.
PMID- 28416519
TI - Time in the Therapeutic Range for Patients Taking Warfarin in Clinical Trials:
Useful, but Also Misleading, Misused, and Overinterpreted.
PMID- 28416520
TI - Engagement, Research, and Evidence: Leveraging the National Patient-Centered
Clinical Research Network for Better Cardiovascular Health.
PMID- 28416516
TI - Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis
of neutrophil-mediated autoimmune vasculitis.
AB - OBJECTIVES: Inappropriate activation of neutrophils plays a pathological role in
antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The aim
of this study was to investigate the functions of semaphorin 4D (SEMA4D) in
regulation of neutrophil activation, and its involvement in AAV pathogenesis.
METHODS: Serum levels of soluble SEMA4D were evaluated by ELISA. Blood cell
surface expression of membrane SEMA4D was evaluated by flow cytometry. To
determine the functional interactions between neutrophil membrane SEMA4D and
endothelial plexin B2, wild-type and SEMA4D-/- mice neutrophils were cultured
with an endothelial cell line (MS1) stained with SYTOX green, and subjected to
neutrophil extracellular trap (NET) formation assays. The efficacy of treating
human neutrophils with recombinant plexin B2 was assessed by measuring the
kinetic oxidative burst and NET formation assays. RESULTS: Serum levels of
soluble SEMA4D were elevated in patients with AAV and correlated with disease
activity scores. Cell-surface expression of SEMA4D was downregulated in
neutrophils from patients with AAV, a consequence of proteolytic cleavage of
membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial
cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells,
and this interaction decreased NET formation. Recombinant plexin B2 suppressed
neutrophil Rac1 activation through SEMA4D's intracellular domain, and inhibited
pathogen-induced or ANCA-induced oxidative burst and NET formation. CONCLUSIONS:
Neutrophil surface SEMA4D functions as a negative regulator of neutrophil
activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may
amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising
biomarker and potential therapeutic target for AAV.
PMID- 28416521
TI - Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): The Past,
Present, and Future Management.
PMID- 28416522
TI - High-Sensitive Cardiac Troponin for Prediction of Clinical Heart Failure: Are We
Ready for Prime Time?
PMID- 28416523
TI - Measuring Pulmonary Artery Pressures in Heart Failure: A New Useful Diagnostic
Tool?
PMID- 28416525
TI - Treatment of Patients With Atrial Fibrillation and Heart Failure With Reduced
Ejection Fraction.
AB - Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF)
frequently coexist, and each complicates the course and treatment of the other.
Recent population-based studies have demonstrated that the 2 conditions together
increase the risk of stroke, heart failure hospitalization, and all-cause
mortality, especially soon after the clinical onset of AF. Guideline-directed
pharmacological therapy for HFrEF is important; however, although there are
various treatment modalities for AF, there is no clear consensus on how best to
treat AF with concomitant HFrEF. This in-depth review discusses the available
data for the treatment of AF in the setting of HFrEF, focuses on areas where more
investigation is necessary, examines the clinical implications of randomized and
observational clinical trials, and presents suggestions for individualized
treatment strategies for specific patient groups.
PMID- 28416524
TI - Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in
Type 1 Diabetes Mellitus.
AB - BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of
cardiovascular complications, but it is unknown to what extent fulfilling all
cardiovascular treatment goals is associated with residual risk of mortality and
cardiovascular outcomes in those with T1DM compared with the general population.
METHODS: We included all patients >=18 years of age with T1DM who were registered
in the Swedish National Diabetes Register from January 1, 1998, through December
31, 2014, a total of 33 333 patients, each matched for age and sex with 5
controls without diabetes mellitus randomly selected from the population.
Patients with T1DM were categorized according to number of risk factors not at
target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density
lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial
infarction, heart failure hospitalization, and stroke was examined in relation to
the number of risk factors at target. RESULTS: The mean follow-up was 10.4 years
in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus
and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for
each additional risk factor not at target. Adjusted hazard ratios for patients
achieving all risk factor targets compared with controls were 1.31 (95%
confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15
2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure
hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for
patients versus controls with none of the risk factors meeting target was 7.33
(95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for
acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure
hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke. CONCLUSIONS: A steep
graded association exists between decreasing number of cardiovascular risk
factors at target and major adverse cardiovascular outcomes among patients with
T1DM. However, risks for all outcomes were numerically higher for patients with
T1DM compared with controls, even when all risk factors were at target, with risk
for acute myocardial infarction and heart failure hospitalization statistically
significantly higher.
PMID- 28416526
TI - Some Common Ground Emerges in Debate Over ECGs for Athletes.
PMID- 28416527
TI - Letter by Irfan Regarding Article, "Assessment of the European Society of
Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute Myocardial
Infarction".
PMID- 28416528
TI - Letter by Mueller and Roffi Regarding Article, "Assessment of the European
Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute
Myocardial Infarction".
PMID- 28416529
TI - Response by Than et al to Letter Regarding Article, "Assessment of the European
Society of Cardiology 0-Hour/1-Hour Algorithm to Rule-Out and Rule-In Acute
Myocardial Infarction".
PMID- 28416530
TI - Letter by Hermida et al Regarding Article, "The Heart's Circadian Rhythms Point
to Potential Treatment Strategies".
PMID- 28416531
TI - Treatment Deintensification Is Uncommon in Adults With Type 2 Diabetes Mellitus:
A Retrospective Cohort Study.
AB - BACKGROUND: Whether treatment deintensification in Americans with diabetes
mellitus varies by glycemic control, health status, and calendar year
(before/after February 2008 when safety concerns about intensive glucose control
were reported in the ACCORD trial [Action to Control Cardiovascular Risk in
Diabetes]) is unclear. METHODS AND RESULTS: We defined deintensification as
discontinuation or dosage decrease of at least 1 glycemic medication without
addition of, or uptitration of, another agent in the 120 days after the index
glycosylated hemoglobin (HbA1C) measurement. Of 99 694 individuals (mean age 54
years) in this retrospective cohort study being actively treated for new diabetes
mellitus (50% 1 drug, 33% 2 drugs, and 17% >=3 drugs), 12 921 (13.0%) had HbA1C
<6% after 1 year, 19 670 (19.7%) had HbA1C 6.0% to 6.4%, 35 012 (35.1%) had HbA1C
6.5% to 7.5%, and 32 091 (32.2%) had HbA1C >7.5%. Glycemic therapy was
deintensified in 18.3% of patients (21.2% of frail patients, 19.4% of those with
multiple comorbidities, and 17.7% of otherwise healthy patients) with no gradient
across glycemia levels (20.6% of those with HbA1C<6%, 17.3% of those with HbA1C
6.0%-6.4%, 17.7% of those with HbA1C 6.5%-7.5%, and 18.6% of those with
HbA1C>7.5%). Similar proportions were seen even after exclusion of 26 985
patients being treated with metformin monotherapy: 23.3%, 20.4%, 20.3%, and 20%
across the HbA1C strata. Therapy was deintensified in 22.5% of patients with
index HbA1C <6.0% before February 2008 compared with 19.5% after (P<0.001).
CONCLUSIONS: Among frail patients or those with multiple comorbidities, over
three quarters with low HbA1C did not have their glycemic therapy deintensified,
even after safety concerns were raised in the ACCORD trial.
PMID- 28416532
TI - Diabetes Mellitus Treatment Deintensification: When Well-Controlled Diabetes
Mellitus Becomes Overcontrolled.
PMID- 28416534
TI - Pazopanib-associated posterior reversible encephalopathy syndrome with
intracerebral haemorrhage.
AB - Pazopanib is a tyrosine kinase receptor antagonist used for renal cell carcinoma
and soft tissue sarcoma that inhibits tumour growth and angiogenesis. A common
side effect of pazopanib is hypertension. We report a case of a 69-year-old woman
with clear cell renal cell carcinoma who developed a large right occipital
intracerebral haemorrhage 3 weeks after initiating pazopanib. Although this was
initially suspected to be a haemorrhagic metastasis, MRI revealed bi-occipital
oedema, supporting a diagnosis of posterior reversible encephalopathy syndrome
(PRES). A craniectomy was required. Immunohistochemical stains for renal cell
carcinoma antigen, CA IX and PAX8 were negative. This case suggests that PRES and
intracerebral haemorrhage may result from pazopanib use and are important
complications to consider prior to initiating this agent.
PMID- 28416535
TI - Pneumatic dental extractions: an unusual cause of extensive cervical surgical
emphysema.
AB - A 50-year-old fit and well man presented to the Accident and Emergency Department
in a tertiary centre following lower molar extraction, complaining of voice
hoarseness with neck and facial swelling. Clinical examination along with plain
film radiography revealed pneumomediastinum and extensive cervical surgical
emphysema. He was subsequently admitted for observation and managed
conservatively under the ENT team with input from the maxillofacial and
anaesthetic teams. With supportive treatment only, the emphysema resolved and he
remained well up until discharge.
PMID- 28416533
TI - Capturing in vivo RNA transcriptional dynamics from the malaria parasite
Plasmodium falciparum.
AB - To capture the transcriptional dynamics within proliferating cells, methods to
differentiate nascent transcription from preexisting mRNAs are desired. One
approach is to label newly synthesized mRNA transcripts in vivo through the
incorporation of modified pyrimidines. However, the human malaria parasite,
Plasmodium falciparum, is incapable of pyrimidine salvage for mRNA biogenesis. To
capture cellular mRNA dynamics during Plasmodium development, we engineered
parasites that can salvage pyrimidines through the expression of a single
bifunctional yeast fusion gene, cytosine deaminase/uracil
phosphoribosyltransferase (FCU). We show that expression of FCU allows for the
direct incorporation of thiol-modified pyrimidines into nascent mRNAs. Using
developmental stage-specific promoters to express FCU-GFP enables the
biosynthetic capture and in-depth analysis of mRNA dynamics from subpopulations
of cells undergoing differentiation. We demonstrate the utility of this method by
examining the transcriptional dynamics of the sexual gametocyte stage transition,
a process that is essential to malaria transmission between hosts. Using the
pfs16 gametocyte-specific promoter to express FCU-GFP in 3D7 parasites, we found
that sexual stage commitment is governed by transcriptional reprogramming and
stabilization of a subset of essential gametocyte transcripts. We also measured
mRNA dynamics in F12 gametocyte-deficient parasites and demonstrate that the
transcriptional program required for sexual commitment and maturation is
initiated but likely aborted due to the absence of the PfAP2-G transcriptional
regulator and a lack of gametocyte-specific mRNA stabilization. Biosynthetic
labeling of Plasmodium mRNAs is incredibly versatile, can be used to measure
transcriptional dynamics at any stage of parasite development, and will allow for
future applications to comprehensively measure RNA-protein interactions in the
malaria parasite.
PMID- 28416536
TI - Multiple jaw cysts and ectopic calcification.
PMID- 28416537
TI - Anosmia with hypogonadism: but NOT Kallmann syndrome.
PMID- 28416538
TI - Susceptibility Testing of Common and Uncommon Aspergillus Species against
Posaconazole and Other Mold-Active Antifungal Azoles Using the Sensititre Method.
AB - We tested 59 common and 27 uncommon Aspergillus species isolates for
susceptibility to the mold-active azole antifungal agents itraconazole,
voriconazole, and posaconazole using the Sensititre method. The overall essential
agreement with the CLSI reference method was 96.5% for itraconazole and
posaconazole and was 100% for voriconazole. By the Sensititre method as well as
the CLSI reference method, all of 10 A. fumigatus isolates with a cyp51 mutant
genotype were classified as being non-wild-type isolates (MIC > epidemiological
cutoff value [ECV]) with respect to triazole susceptibility.
PMID- 28416539
TI - Comparison of EUCAST and CLSI Reference Microdilution MICs of Eight Antifungal
Compounds for Candida auris and Associated Tentative Epidemiological Cutoff
Values.
AB - Candida auris is an emerging multidrug-resistant yeast. So far, all but two
susceptibility testing studies have examined <=50 isolates, mostly with the CLSI
method. We investigated CLSI and EUCAST MICs for 123 C. auris isolates and eight
antifungals and evaluated various methods for epidemiological cutoff (ECOFF)
determinations. MICs (in milligrams per liter) were determined using CLSI method
M27-A3, and the EUCAST E.Def 7.3. ANOVA analysis of variance with Bonferroni's
multiple-comparison test and Pearson analysis were used on log2 MICs
(significance at P values of <0.05). The percent agreement (within +/-0 to +/-2 2
fold dilutions) between the methods was calculated. ECOFFs were determined
visually, statistically (using the ECOFF Finder program and MicDat1.23 software
with 95% to 99% endpoints), and via the derivatization method (dECOFFs). The CLSI
and EUCAST MIC distributions were wide, with several peaks for all compounds
except amphotericin B, suggesting possible acquired resistance. Modal MIC,
geometric MIC, MIC50, and MIC90 values were <=1 2-fold dilutions apart, and no
significant differences were found. The quantitative agreement was best for
amphotericin B (80%/97% within +/-1/+/-2 dilutions) and lowest for isavuconazole
and anidulafungin (58%/76% to 75% within +/-1/+/-2 dilutions). We found that
90.2%/100% of the isolates were amphotericin B susceptible based on CLSI/EUCAST
methods, respectively (i.e., with MICs of <=1 mg/liter), and 100%/97.6% were
fluconazole nonsusceptible by CLSI/EUCAST (MICs > 2). The ECOFFs (in milligrams
per liter) were similar across the three different methods for itraconazole
(ranges for CLSI/EUCAST, 0.25 to 0.5/0.5 to 1), posaconazole (0.125/0.125 to
0.25), amphotericin B (0.25 to 0.5/1 to 2), micafungin (0.25 to 0.5), and
anidulafungin (0.25 to 0.5/0.25 to 1). In contrast, the estimated ECOFFs were
dependent on the method applied for voriconazole (1 to 32) and isavuconazole
(0.125 to 4). CLSI and EUCAST MICs were remarkably similar and confirmed uniform
fluconazole resistance and variable acquired resistance to the other agents.
PMID- 28416541
TI - Efflux Attenuates the Antibacterial Activity of Q203 in Mycobacterium
tuberculosis.
AB - New and improved treatments for tuberculosis (TB) are urgently needed. Recently,
it has been demonstrated that verapamil, an efflux inhibitor, can reduce
bacterial drug tolerance caused by efflux pump activity when administered in
combination with available antituberculosis agents. The aim of this study was to
evaluate the effectiveness of verapamil in combination with the antituberculosis
drug candidate Q203, which has recently been developed and is currently under
clinical trials as a potential antituberculosis agent. We evaluated changes in
Q203 activity in the presence and absence of verapamil in vitro using the
resazurin microplate assay and ex vivo using a microscopy-based phenotypic assay
for the quantification of intracellular replicating mycobacteria. Verapamil
increased the potency of Q203 against Mycobacterium tuberculosis both in vitro
and ex vivo, indicating that efflux pumps are associated with the activity of
Q203. Other efflux pump inhibitors also displayed an increase in Q203 potency,
strengthening this hypothesis. Therefore, the combination of verapamil and Q203
may be a promising combinatorial strategy for anti-TB treatment to accelerate the
elimination of M. tuberculosis.
PMID- 28416540
TI - In Vivo Efficacy of Liposomal Amphotericin B against Wild-Type and Azole
Resistant Aspergillus fumigatus Isolates in Two Different Immunosuppression
Models of Invasive Aspergillosis.
AB - Using an immunocompetent murine model of invasive aspergillosis (IA), we
previously reported that the efficacy of liposomal amphotericin B (L-AmB)
(Ambisome) is not hampered by the presence of azole resistance mutations in
Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P.
E. Verweij, Antimicrob Agents Chemother 57:1866-1871, 2013,
https://doi.org/10.1128/AAC.02226-12). We here investigated the role of immune
suppression, i.e., neutropenia and steroid treatment, in L-AmB efficacy in mice
infected with wild-type (WT) A. fumigatus and with azole-resistant A. fumigatus
harboring a TR34/L98H mutation in the cyp-51A gene. Survival of treated animals
at day 14 in both immunosuppressed models was significantly better than that of
nontreated controls. A dose-response relationship was observed that was
independent of the azole-resistant mechanism and the immunosuppression method
used. In the neutropenic model, 100% survival was reached at an L-AmB dose of 16
mg/kg of body weight for the WT strain and the TR34/L98H isolate. In the steroid
treated group, 90.9% survival and 100% survival were achieved for the WT isolate
and the TR34/L98H isolate with an L-AmB dose of 16 mg/kg, respectively. The 50%
effective dose (ED50) was 1.40 mg/kg (95% confidence interval [CI], 0.66 to 3.00
mg/kg) for the WT isolate and 1.92 mg/kg (95% CI, 0.60 to 6.17 mg/kg) for the
TR34/L98H isolate in the neutropenic model and was 2.40 mg/kg (95% CI, 1.93 to
2.97 mg/kg) for the WT isolate and 2.56 mg/kg (95% CI, 1.43 to 4.56 mg/kg) for
the TR34/L98H isolate in the steroid-treated group. Overall, there were no
significant differences between the two different immunosuppressed conditions in
the efficacy of L-AmB against the wild-type and azole-resistant isolates (P >
0.9). However, the required L-AmB exposure was significantly higher than that
seen in the immunocompetent model.
PMID- 28416542
TI - High-Resolution Melting Analysis for Rapid Detection of Sequence Type 131
Escherichia coli.
AB - Escherichia coli isolates belonging to the sequence type 131 (ST131) clonal
complex have been associated with the global distribution of fluoroquinolone and
beta-lactam resistance. Whole-genome sequencing and multilocus sequence typing
identify sequence type but are expensive when evaluating large numbers of
samples. This study was designed to develop a cost-effective screening tool using
high-resolution melting (HRM) analysis to differentiate ST131 from non-ST131 E.
coli in large sample populations in the absence of sequence analysis. The method
was optimized using DNA from 12 E. coli isolates. Singleplex PCR was performed
using 10 ng of DNA, Type-it HRM buffer, and multilocus sequence typing primers
and was followed by multiplex PCR. The amplicon sizes ranged from 630 to 737 bp.
Melt temperature peaks were determined by performing HRM analysis at 0.1 degrees
C resolution from 50 to 95 degrees C on a Rotor-Gene Q 5-plex HRM system.
Derivative melt curves were compared between sequence types and analyzed by
principal component analysis. A blinded study of 191 E. coli isolates of ST131
and unknown sequence types validated this methodology. This methodology returned
99.2% specificity (124 true negatives and 1 false positive) and 100% sensitivity
(66 true positives and 0 false negatives). This HRM methodology distinguishes
ST131 from non-ST131 E. coli without sequence analysis. The analysis can be
accomplished in about 3 h in any laboratory with an HRM-capable instrument and
principal component analysis software. Therefore, this assay is a fast and cost
effective alternative to sequencing-based ST131 identification.
PMID- 28416543
TI - Potential Toxicity of Polymyxins in Human Lung Epithelial Cells.
AB - Inhaled polymyxins are of considerable utility in achieving optimal exposure in
the respiratory tract for the treatment of lung infections caused by multidrug
resistant Gram-negative pathogens. Current inhaled polymyxin therapy is
empirical, and often large doses are used that may lead to potential pulmonary
adverse effects. This study aimed to investigate the effect of polymyxins on
human lung epithelial (A549) cells. The viability of A549 cells was examined
after treatment with polymyxins by flow cytometry. Activation of caspases 3, 8,
and 9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential,
and mitochondrial oxidative stress induced by polymyxin B were evaluated. The
concentration of polymyxin B required to induce 50% of maximal cell death was
1.74 mM (95% confidence interval, 1.60 to 1.90 mM). Colistin was at least 2-fold
less toxic than polymyxin B, while colistimethate was nontoxic. With 2.0 mM
polymyxin B, 30.6% +/- 11.5% (mean +/- standard deviation) of the cells were
apoptotic at 8 h and this increased to 71.3% +/- 3.72% at 24 h. Concentration-
and time-dependent activation of caspases 3, 8, and 9 was evident, while the
activation of caspase 9 was more dramatic. Furthermore, polymyxin B caused
concentration- and time-dependent FasL expression, production of mitochondrial
reactive oxygen species, and changes in mitochondrial membrane potential. This is
the first study to demonstrate that both extrinsic death receptor and intrinsic
mitochondrial pathways are involved in polymyxin-induced toxicity in A549 cells.
This knowledge base is critical for the development of novel strategies for the
safe and effective inhalation therapy of polymyxins against Gram-negative
"superbugs."
PMID- 28416544
TI - Deciphering Heteroresistance to Colistin in a Klebsiella pneumoniae Isolate from
Marseille, France.
AB - Here, we report the description of a colistin-heteroresistant Klebsiella
pneumoniae isolate fortuitously isolated from the stool sample of a patient with
suspicion of tuberculosis in a public hospital of Marseille, France. In the
colistin-resistant subpopulation, a mutation in the mgrB gene leading to a
premature stop codon was found, and the hypermucoviscous phenotype was lost.
Susceptibility to other antibiotics remained unchanged. To our knowledge, this is
the first identification of such a colistin-heteroresistant Klebsiella pneumoniae
isolate in France.
PMID- 28416545
TI - Dissemination of mcr-1-Carrying Plasmids among Colistin-Resistant Salmonella
Strains from Humans and Food-Producing Animals in Taiwan.
AB - We detected the colistin resistance gene mcr-1 in four Salmonella serovars
isolated from humans and animals with diarrhea. The resistance gene was carried
on different plasmids. One mcr-1-carrying conjugative plasmid, a variant of
pHNSHP45, was disseminated among Salmonella isolates recovered from humans, pigs,
and chickens.
PMID- 28416546
TI - Anti-influenza Activity of a Bacillus subtilis Probiotic Strain.
AB - Among Bacillus bacteria, B. subtilis is the species that produces the most
antimicrobial compounds. In this study, we analyzed the activity of probiotic
strain B. subtilis 3 against the influenza virus. The antiviral effect of this
strain has been demonstrated in vitro and in vivo A new peptide, P18, produced by
the probiotic strain was isolated, purified, chemically synthesized, and
characterized. Cytotoxicity studies demonstrated no toxic effect of P18 on Madin
Darby canine kidney (MDCK) cells, even at the highest concentration tested (100
MUg/ml). Complete inhibition of the influenza virus in vitro was observed at
concentrations of 12.5 to 100 MUg/ml. The protective effect of P18 in mice was
comparable to that of oseltamivir phosphate (Tamiflu). Further study will assess
the potential of peptide P18 as an antiviral compound and as a promising
candidate for the development of new antiviral vaccines.
PMID- 28416547
TI - Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based
Pharmacokinetic Model for Tenofovir Disoproxil Fumarate.
AB - Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, has oral
bioavailability (25%) limited by intestinal transport (P-glycoprotein), and
intestinal degradation (carboxylesterase). However, the influence of luminal
pancreatic enzymes is not fully understood. Physiologically based pharmacokinetic
(PBPK) modeling has utility for estimating drug exposure from in vitro data. This
study aimed to develop a PBPK model that included luminal enzyme activity to
inform dose reduction strategies. TDF and tenofovir stability in porcine
pancrelipase concentrations was assessed (0, 0.48, 4.8, 48, and 480 U/ml of
lipase; 1 mM TDF; 37 degrees C; 0 to 30 min). Samples were analyzed using mass
spectrometry. TDF stability and permeation data allowed calculation of absorption
rates within a human PBPK model to predict plasma exposure following 6 days of
once-daily dosing with 300 mg of TDF. Regional absorption of drug was simulated
across gut segments. TDF was degraded by pancrelipase (half-lives of 0.07 and
0.62 h using 480 and 48 U/ml, respectively). Previously reported maximum
concentration (Cmax; 335 ng/ml), time to Cmax (Tmax; 2.4 h), area under the
concentration-time curve from 0 to 24 h (AUC0-24; 3,045 ng . h/ml), and
concentration at 24 h (C24; 48.3 ng/ml) were all within a 0.5-fold difference
from the simulated Cmax (238 ng/ml), Tmax (3 h), AUC0-24 (3,036 ng . h/ml), and
C24 (42.7 ng/ml). Simulated TDF absorption was higher in duodenum and jejunum
than in ileum (p<0.05). These data support that TDF absorption is limited by the
action of intestinal lipases. Our results suggest that bioavailability may be
improved by protection of drug from intestinal transporters and enzymes, for
example, by coadministration of enzyme-inhibiting agents or nanoformulation
strategies.
PMID- 28416548
TI - Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the
Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.
AB - The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of
known human immunodeficiency virus type 1 (HIV-1) isolates in vitro, is a
promising candidate microbicide for preventing sexual HIV infection when
administered topically to the vagina; however, accessibility to antibody-based
prophylactic treatment by target populations in sub-Saharan Africa and other
underdeveloped regions may be limited by the high cost of conventionally produced
antibodies and the limited capacity to manufacture such antibodies. Intravaginal
rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01 (VRC01
N) over a range of release rates have been developed. The pharmacokinetics and
preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model.
The devices sustained VRC01-N release for up to 21 days at controlled rates, with
mean steady-state VRC01-N levels in vaginal fluids in the range of 102 to 103 MUg
g-1 being correlated with in vitro release rates. No adverse safety indications
were observed. These findings indicate that pod-IVRs are promising devices for
the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection
and merit further preclinical evaluation.
PMID- 28416549
TI - Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor
Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.
AB - Although genotype 4 (GT4)-infected patients represent a minor overall percentage
of the global hepatitis C virus (HCV)-infected population, the high prevalence of
the genotype in specific geographic regions coupled with substantial sequence
diversity makes it an important genotype to study for antiviral drug discovery
and development. We evaluated two direct-acting antiviral agents-grazoprevir, an
HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4
replicons prior to clinical studies in this genotype. Following a bioinformatics
analysis of available GT4 sequences, a set of replicons bearing representative
GT4 clinical isolates was generated. For grazoprevir, the 50% effective
concentration (EC50) against the replicon bearing the reference GT4a (ED43) NS3
protease and NS4A was 0.7 nM. The median EC50 for grazoprevir against chimeric
replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range,
0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A
resistance-associated substitutions was substantially overcome with the
identification of a G162R adaptive substitution in NS3. Single NS3 substitutions
D168A/V identified from de novo resistance selection studies reduced grazoprevir
antiviral activity by 137- and 47-fold, respectively, in the background of the
G162R replicon. For elbasvir, the EC50 against the replicon bearing the reference
full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC50 for elbasvir
against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM
(range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4
demonstrated a high propensity to suppress the emergence of amino acid
substitutions that confer high-potency reductions to elbasvir. Phenotypic
characterization of the NS5A amino acid substitutions identified (L30F, L30S,
M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency
losses, respectively, to elbasvir. The activity profiles of grazoprevir and
elbasvir supported the testing of the direct-acting antivirals in clinical
studies.
PMID- 28416550
TI - Identification and Optimization of Thienopyridine Carboxamides as Inhibitors of
HIV Regulatory Complexes.
AB - Viral regulatory complexes perform critical functions during virus replication
and are important targets for therapeutic intervention. In HIV, the Tat and Rev
proteins form complexes with multiple viral and cellular factors to direct
transcription and export of the viral RNA. These complexes are composed of many
proteins and are dynamic, making them difficult to fully recapitulate in vitro
Therefore, we developed a cell-based reporter assay to monitor the assembly of
viral complexes for inhibitor screening. We screened a small-molecule library and
identified multiple hits that inhibit the activity of the viral complexes. A
subsequent chemistry effort was focused on a thieno[2,3-b]pyridine scaffold,
examples of which inhibited HIV replication and the emergence from viral latency.
Notable aspects of the effort to determine the structure-activity relationship
(SAR) include migration to the regioisomeric thieno[2,3-c]pyridine ring system
and the identification of analogs with single-digit nanomolar activity in both
reporter and HIV infectivity assays, an improvement of >100-fold in potency over
the original hits. These results validate the screening strategy employed and
reveal a promising lead series for the development of a new class of HIV
therapeutics.
PMID- 28416551
TI - Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic
Murine Thigh and Lung Infection Models against Staphylococcus aureus.
AB - The pharmacodynamics of telavancin and vancomycin were compared using neutropenic
murine thigh and lung infection models. Four Staphylococcus aureus strains were
included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the
vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of
escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and
vancomycin were linear over the dose range. Epithelial lining fluid (ELF)
pharmacokinetics for each drug revealed that penetration into the ELF mirrored
the percentage of the free fraction (the fraction not protein bound) in plasma
for each drug. Telavancin (0.3125 to 80 mg/kg/6 h) and vancomycin (0.3125 to
1,280 mg/kg/6 h) were administered by the subcutaneous route in treatment
studies. Dose-dependent bactericidal activity against all four strains was
observed in both models. A sigmoid maximum-effect model was used to determine the
area under the concentration-time curve (AUC)/MIC exposure associated with net
stasis and 1-log10 kill relative to the burden at the start of therapy. The 24-h
plasma free drug AUC (fAUC)/MIC values associated with stasis and 1-log kill were
remarkably congruent. Net stasis for telavancin was noted at fAUC/MIC values of
83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at
fAUC/MIC values of 215 and 76.4, respectively. For vancomycin, the fAUC/MIC
values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were
282 and 113, respectively. The 24-h ELF total drug AUC/MIC targets in the lung
model were very similar to the 24-h plasma free drug AUC/MIC targets for each
drug. Integration of human pharmacokinetic data for telavancin, the results of
the MIC distribution studies, and the pharmacodynamic targets identified in this
study suggests that the current dosing regimen of telavancin is optimized to
obtain drug exposures sufficient to treat S. aureus infections.
PMID- 28416552
TI - In Vivo Pharmacodynamic Target Assessment of Eravacycline against Escherichia
coli in a Murine Thigh Infection Model.
AB - Eravacycline is a novel fluorocycline antibiotic with potent activity against a
broad range of pathogens, including strains with tetracycline and other drug
resistance phenotypes. The goal of the studies was to determine which
pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated
with efficacy in the murine thigh infection model. Six Escherichia coli isolates
were utilized for the studies. MICs were determined using CLSI methods and ranged
from 0.125 to 0.25 mg/liter. A neutropenic murine thigh infection model was
utilized for all treatment studies. Single-dose plasma pharmacokinetics were
determined in mice after administration of 2.5, 5, 10, 20, 40, and 80 mg/kg of
body weight. Pharmacokinetic studies exhibited maximum plasma concentration
(Cmax) values of 0.34 to 2.58 mg/liter, area under the concentration-time curve
(AUC) from time zero to infinity (AUC0-infinity) values of 2.44 to 57.6 mg .
h/liter, and elimination half-lives of 3.9 to 17.6 h. Dose fractionation studies
were performed using total drug doses of 6.25 mg/kg to 100 mg/kg fractionated
into 6-, 8-, 12-, or 24-h regimens. Nonlinear regression analysis demonstrated
that the 24-h free drug AUC/MIC (fAUC/MIC) was the PK/PD parameter that best
correlated with efficacy (R2 = 0.80). In subsequent studies, we used the
neutropenic murine thigh infection model to determine if the magnitude of the
AUC/MIC needed for the efficacy of eravacycline varied among pathogens. Mice were
treated with 2-fold increasing doses (range, 3.125 to 50 mg/kg) of eravacycline
every 12 h. The mean fAUC/MIC magnitudes associated with the net stasis and the 1
log-kill endpoints were 27.97 +/- 8.29 and 32.60 +/- 10.85, respectively.
PMID- 28416553
TI - Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically
Ill Patient on Continuous Venovenous Hemofiltration.
AB - Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat
multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient
on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug
concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8
h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6.
Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively,
were as follows: maximum plasma concentration (Cmax), 61.10 and 14.54 mg/liter;
minimum plasma concentration (Cmin), 31.96 and 8.45 mg/liter; half-life (t1/2),
6.07 and 6.78 h; apparent volume of distribution at the steady state (Vss), 27.23
and 30.81 liters; total clearance at the steady state (CLss), 2.87 and 2.95
liters/h; area under the concentration-time curve from 0 to 8 h (AUC0-8), 347.87
and 85.69 mg . h/liter. Concentrations of ceftazidime in plasma exceeded the
ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean
CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%,
respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The
calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for
avibactam was 1.59 liters/h, representing 57.1% of the total clearance of
ceftazidime and 54.3% of the total clearance of avibactam. Further data that
include multiple patients and dialysis modes are needed to verify the optimal
ceftazidime-avibactam dosing strategy during critical illness and CVVH.
PMID- 28416554
TI - In Vitro Study of ISApl1-Mediated Mobilization of the Colistin Resistance Gene
mcr-1.
AB - The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase that
confers resistance to polymyxins. The mcr-1 gene is associated with insertion
sequence ISApl1 (IS30 family). In vitro mobilization assays demonstrated the
functionality of the composite transposon structure ISApl1-mcr-1-ISApl1
Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions.
This is the first report demonstrating the mobility of the mcr-1 gene by
transposition.
PMID- 28416555
TI - Mycobacterium tuberculosis Proteome Response to Antituberculosis Compounds
Reveals Metabolic "Escape" Pathways That Prolong Bacterial Survival.
AB - Tuberculosis (TB) continues to be one of the most common bacterial infectious
diseases and is the leading cause of death in many parts of the world. A major
limitation of TB therapy is slow killing of the infecting organism, increasing
the risk for the development of a tolerance phenotype and drug resistance.
Studies indicate that Mycobacterium tuberculosis takes several days to be killed
upon treatment with lethal concentrations of antibiotics both in vitro and in
vivo To investigate how metabolic remodeling can enable transient bacterial
survival during exposure to bactericidal concentrations of compounds, M.
tuberculosis strain H37Rv was exposed to twice the MIC of isoniazid, rifampin,
moxifloxacin, mefloquine, or bedaquiline for 24 h, 48 h, 4 days, and 6 days, and
the bacterial proteomic response was analyzed using quantitative shotgun mass
spectrometry. Numerous sets of de novo bacterial proteins were identified over
the 6-day treatment. Network analysis and comparisons between the drug treatment
groups revealed several shared sets of predominant proteins and enzymes
simultaneously belonging to a number of diverse pathways. Overexpression of some
of these proteins in the nonpathogenic Mycobacterium smegmatis extended bacterial
survival upon exposure to bactericidal concentrations of antimicrobials, and
inactivation of some proteins in M. tuberculosis prevented the pathogen from
escaping the fast killing in vitro and in macrophages, as well. Our biology
driven approach identified promising bacterial metabolic pathways and enzymes
that might be targeted by novel drugs to reduce the length of tuberculosis
therapy.
PMID- 28416556
TI - Colistin-Resistant mcr-1-Positive Escherichia coli on Public Beaches, an
Infectious Threat Emerging in Recreational Waters.
AB - The emergence and rapid spread of colistin-resistant Escherichia coli carrying
the mcr-1 gene have generated an urgent need to strengthen surveillance. We
performed a meticulous investigation of strains of this sort, which resulted in
the identification of international clones of E. coli carrying IncX4-plasmid
mediated mcr-1 and blaCTX-M genes in recreational waters of public urban beaches
in cities with high tourist turnover, highlighting a new environmental reservoir.
PMID- 28416557
TI - Terbinafine Resistance of Trichophyton Clinical Isolates Caused by Specific Point
Mutations in the Squalene Epoxidase Gene.
AB - Terbinafine is one of the allylamine antifungal agents whose target is squalene
epoxidase (SQLE). This agent has been extensively used in the therapy of
dermatophyte infections. The incidence of patients with tinea pedis or unguium
tolerant to terbinafine treatment prompted us to screen the terbinafine
resistance of all Trichophyton clinical isolates from the laboratory of the
Centre Hospitalier Universitaire Vaudois collected over a 3-year period and to
identify their mechanism of resistance. Among 2,056 tested isolates, 17 (~1%)
showed reduced terbinafine susceptibility, and all of these were found to harbor
SQLE gene alleles with different single point mutations, leading to single amino
acid substitutions at one of four positions (Leu393, Phe397, Phe415, and His440)
of the SQLE protein. Point mutations leading to the corresponding amino acid
substitutions were introduced into the endogenous SQLE gene of a terbinafine
sensitive Arthroderma vanbreuseghemii (formerly Trichophyton mentagrophytes)
strain. All of the generated A. vanbreuseghemii transformants expressing mutated
SQLE proteins exhibited obvious terbinafine-resistant phenotypes compared to the
phenotypes of the parent strain and of transformants expressing wild-type SQLE
proteins. Nearly identical phenotypes were also observed in A. vanbreuseghemii
transformants expressing mutant forms of Trichophyton rubrum SQLE proteins.
Considering that the genome size of dermatophytes is about 22 Mb, the frequency
of terbinafine-resistant clinical isolates was strikingly high. Increased
exposure to antifungal drugs could favor the generation of resistant strains.
PMID- 28416558
TI - In Vitro Discordance with In Vivo Activity: Humanized Exposures of Ceftazidime
Avibactam, Aztreonam, and Tigecycline Alone and in Combination against New Delhi
Metallo-beta-Lactamase-Producing Klebsiella pneumoniae in a Murine Lung Infection
Model.
AB - The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)
producing bacteria remains clinically challenging given the multidrug resistant
(MDR) phenotype associated with these bacteria. Despite resistance in vitro,
ceftazidime-avibactam previously demonstrated in vivo activity against NDM
positive Enterobacteriaceae Herein, we observed in vitro synergy with ceftazidime
avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In
vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10
CFU bacterial reduction; therefore, no in vivo synergy was observed.
PMID- 28416560
TI - Horizontal schools-based health programme in rural Kenya.
AB - BACKGROUND: Primary school children in low-income countries are at risk of many
diseases and poor health affects attendance, cognition and ability to learn.
Developing school health and nutrition strategies has been extensively
highlighted as a global priority, with a particular focus on complex programme
design. However, such programmes are relatively untested in low-income settings.
METHOD: We implemented a complex school health and nutrition programme in two
schools in Western Kenya over 3 years. There were numerous elements covering
health policy, skills-based health education, infrastructure and disease
prevention. A local non-governmental organisation, with involvement from local
government and the community, performed programme implementation. Height-for-age,
weight-for-age,height-for-weight, anaemia prevalence, academic performance and
school attendance were the primary outcome measures. RESULTS: The programme
improved nutrition, academic performance and anaemia prevalence. The number of
underweight children fell from 20% to 11% (OR 0.51 95% CI 0.39 to 0.68 p=<0.01)
and stunting prevalence fell from 29.9% to 20% (OR 0.59 95% CI 0.50 to 0.68
p=<0.01). Academic performance improved with a 74% reduction in odds of failing
assessments (OR 0.26 95% CI 0.22 to 0.29 p=<0.01). Anaemia prevalence fell from
17.2% to 11%. The programme showed an increase in low body mass index prevalence
and no effect on school attendance, the reasons for which are unclear.
DISCUSSION: These results are encouraging and demonstrate that complex schools
health programmes can lead to positive gains in health, nutrition and importantly
academic performance. There is a need for further evaluation of comprehensive
school health interventions in poor communities.
PMID- 28416559
TI - A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention
of Intraluminal Central Venous Catheter Infections in Cancer Patients.
AB - For long-term central lines (CL), the lumen is the major source of central line
associated bloodstream infections (CLABSI). The current standard of care for
maintaining catheter patency includes flushing the CL with saline or heparin.
Neither agent has any antimicrobial activity. Furthermore, heparin may enhance
staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel
nonantibiotic catheter lock solution for the prevention of CLABSI. Between
November 2015 and February 2016, we enrolled 60 patients with hematologic
malignancies who had peripherally inserted central catheters (PICC) to receive
the study lock solution. The study lock consisted of 15 or 30 MUg/ml of
nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen
was locked for at least 2 h once daily prior to being flushed. After enrollment
of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the
dose was escalated to the higher dose (30 MUg/ml). There were no serious related
adverse events or episodes of hypotension with lock administration. Two patients
experienced mild transient adverse events (one headache and one rash) possibly
related to the lock and that resolved without residual effect. The CLABSI rate
was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis,
compared with a rate of 1.9/1,000 CD at the institution in the same patient
population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and
well tolerated. It may prevent CLABSI when given daily to cancer patients. Large,
prospective, randomized clinical trials are needed to validate these findings.
(This study has been registered at ClinicalTrials.gov under identifier
NCT02577718.).
PMID- 28416561
TI - Requirements for and current provision of rehabilitation services for children
after severe acquired brain injury in the UK: a population-based study.
AB - OBJECTIVES: Survival with brain injury is an outcome of severe illness that may
be becoming more common. Provision for children in this situation has received
little attention. We sought to estimate rates of severe paediatric acquired brain
injury (ABI) requiring rehabilitation and to describe current provision of
services for these children in the UK. METHODS: This study conducted an analysis
of Hospital Episode Statistics data between April 2003 and March 2012,
supplemented by a UK provider survey completed in 2015. A probable severe ABI
requiring rehabilitation (PSABIR) event was inferred from the co-occurrence of a
medical condition likely to cause ABI (such as meningitis) and a prolonged
inpatient stay (>=28 days). RESULTS: During the period studied, 4508 children
aged 1-18 years in England had PSABIRs. Trauma was the most common cause (30%)
followed by brain tumours (19%) and anoxia (18.3%). An excess in older males was
attributable to trauma. We estimate the incidence of PSABIR to be at least 2.93
(95%CI 2.62 to 3.26) per 100 000 young people (1-18 years) pa. The provider
survey confirmed marked geographic variability in the organisation of services in
the UK. CONCLUSIONS: There are at least 350 PSABIR events in children in the UK
annually, a health problem of similar magnitude to that of cerebral palsy.
Service provision for this population varies widely around the UK, in contrast
with the nationally coordinated approach to paediatric intensive care and major
trauma provision.
PMID- 28416562
TI - Henry Head, herpes zoster and the graphic development of his 'scheme of the
dermatomes in man'.
PMID- 28416563
TI - Home-based therapy for chronic Wernicke's aphasia.
PMID- 28416564
TI - The London Contribution to Neurology and Psychiatry: The second British Symposium
on the History of Neurology and Psychiatry.
PMID- 28416565
TI - Cingulo-insular structural alterations associated with psychogenic symptoms,
childhood abuse and PTSD in functional neurological disorders.
AB - OBJECTIVE: Adverse early-life events are predisposing factors for functional
neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo
insular regions are implicated in the biology of both conditions and are sites of
stress-mediated neuroplasticity. We hypothesised that functional neurological
symptoms and the magnitude of childhood abuse would be associated with
overlapping anterior cingulate cortex (ACC) and insular volumetric reductions,
and that FND and PTSD symptoms would map onto distinct cingulo-insular areas.
METHODS: This within-group voxel-based morphometry study probes volumetric
associations with self-report measures of functional neurological symptoms,
adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate
secondary analyses were also performed in the subset of 18 women with FND to
account for gender-specific effects. RESULTS: Across the entire cohort, there
were no statistically significant volumetric associations with self-report
measures of functional neurological symptom severity or childhood abuse. In women
with FND, however, parallel inverse associations were observed between left
anterior insular volume and functional neurological symptoms as measured by the
Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms
Conversion Disorder subscale. Similar inverse relationships were also appreciated
between childhood abuse burden and left anterior insular volume. Across all
subjects, PTSD symptom severity was inversely associated with dorsal ACC volume,
and the magnitude of lifetime adverse events was inversely associated with left
hippocampal volume. CONCLUSIONS: This study reveals distinct cingulo-insular
alterations for FND and PTSD symptoms and may advance our understanding of FND.
Potential biological convergence between stress-related neuroplasticity,
functional neurological symptoms and reduced insular volume was identified.
PMID- 28416566
TI - Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of
hairpins and motif Va in translocation along RNA.
AB - Three families of nucleic acid-dependent ATPases (DEAH/RHA, Ski2-like, and
NS3/NPH-II), termed the DExH ATPases, are thought to execute myriad functions by
processive, ATP-dependent, 3' to 5' translocation along single-stranded nucleic
acid. While the mechanism of translocation of the viral NS3/NPH-II family has
been studied extensively, it has not been clear if or how the principles that
have emerged for this family extend to the other two families. Here we report the
crystal structure of the yeast DEAH/RHA family ATPase Prp43p, which functions in
splicing and ribosome biogenesis, in complex with poly-uracil and a
nonhydrolyzable ATP analog. The structure reveals a conserved DEAH/RHA-specific
variation of motif Ib within the RecA1 domain of the catalytic core, in which the
motif elongates as a beta-hairpin that bookends the 3' end of a central RNA
stack, a function that in the viral and Ski-2 families is performed by an
auxiliary domain. Supporting a fundamental role in translocation, mutations in
this hairpin abolished helicase activity without affecting RNA binding or ATPase
activity. While the structure reveals differences with viral ATPases in the RecA1
domain, our structure demonstrates striking similarities with viral ATPases in
the RecA2 domain of the catalytic core, including both a prominent beta-hairpin
that bookends the 5' end of the RNA stack and a dynamic motif Va that is
implicated in mediating translocation. Our crystal structure, genetic, and
biochemical experiments, as well as comparisons with other DExH ATPases, support
a generalized mechanism for the DExH class of helicases involving a pair of
bookends that inchworm along RNA.
PMID- 28416567
TI - The C-terminal dsRNA-binding domain of Drosophila Dicer-2 is crucial for
efficient and high-fidelity production of siRNA and loading of siRNA to
Argonaute2.
AB - Drosophila Dicer-2 efficiently and precisely produces 21-nucleotide (nt) siRNAs
from long double-stranded RNA (dsRNA) substrates and loads these siRNAs onto the
effector protein Argonaute2 for RNA silencing. The functional roles of each
domain of the multidomain Dicer-2 enzyme in the production and loading of siRNAs
are not fully understood. Here we characterized Dicer-2 mutants lacking either
the N-terminal helicase domain or the C-terminal dsRNA-binding domain (CdsRBD)
(DeltaHelicase and DeltaCdsRBD, respectively) in vivo and in vitro. We found that
DeltaCdsRBD Dicer-2 produces siRNAs with lowered efficiency and length fidelity,
producing a smaller ratio of 21-nt siRNAs and higher ratios of 20- and 22-nt
siRNAs in vivo and in vitro. We also found that DeltaCdsRBD Dicer-2 cannot load
siRNA duplexes to Argonaute2 in vitro. Consistent with these findings, we found
that DeltaCdsRBD Dicer-2 causes partial loss of RNA silencing activity in vivo.
Thus, Dicer-2 CdsRBD is crucial for the efficiency and length fidelity in siRNA
production and for siRNA loading. Together with our previously published
findings, we propose that CdsRBD binds the proximal body region of a long dsRNA
substrate whose 5'-monophosphate end is anchored by the phosphate-binding pocket
in the PAZ domain. CdsRBD aligns the RNA to the RNA cleavage active site in the
RNase III domain for efficient and high-fidelity siRNA production. This study
reveals multifunctions of Dicer-2 CdsRBD and sheds light on the molecular
mechanism by which Dicer-2 produces 21-nt siRNAs with a high efficiency and
fidelity for efficient RNA silencing.
PMID- 28416569
TI - Association between smoking and health outcomes in an economically deprived
population: the Liverpool Lung Project.
AB - BACKGROUND: The association between smoking and several health outcomes among
those from the most deprived communities in the UK has not previously been
detailed. The aim of this study is to examine the impact of smoking on health
outcomes specifically among a particularly deprived population in a developed
country (Liverpool; one of the most deprived local authorities in England).
METHODS: The Liverpool Lung Project recruited a prospective cohort of 8753
participants from across Liverpool, aged 45-79 years between 1998 and 2008.
Participants were followed annually through the Hospital Episode Statistics until
31 January 2013. Logistic regression models were used to identify health outcomes
of smoking. RESULTS: From our study population, 5195 were smokers and 3558 were
non-smokers. Smoking was associated with male gender (OR 1.62, 95% CI 1.48 to
1.77), pneumonia (1.28, 95% CI 1.10 to 1.49), chronic obstructive pulmonary
disease (1.30, 95% CI 1.14 to 1.48), emphysema (5.46, 95% CI 3.48 to 8.55),
bronchitis (1.85, 95% CI 1.65 to 2.07), other cancers (1.69, 95% CI 1.44 to
1.99), lung cancer (6.0, 95% CI 3.72 to 9.69), diabetes (1.21, 95% CI 1.02 to
1.43) and cardiovascular disease (1.45, 95% CI 1.25 to 1.67). CONCLUSIONS:
Smokers from deprived backgrounds in Liverpool showed increased risk of
developing pneumonia, emphysema, chronic obstructive pulmonary disease,
bronchitis, lung cancer, other types of cancer, cardiovascular disease and
diabetes. These findings are in line with the literature and may help to inform
public health policies and ultimately work towards addressing smoking-related
health inequalities.
PMID- 28416568
TI - Pharmacological and Toxicological Properties of the Potent Oral gamma-Secretase
Modulator BPN-15606.
AB - Alzheimer's disease (AD) is characterized neuropathologically by an abundance of
1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid
amyloid-beta peptide (Abeta), as well as 2) neurofibrillary tangles composed of
aggregates of hyperphosporylated tau. Elevations in the concentrations of the
Abeta42 peptide in the brain, as a result of either increased production or
decreased clearance, are postulated to initiate and drive the AD pathologic
process. We initially introduced a novel class of bridged aromatics referred
tgamma-secretase modulatoro as gamma-secretase modulators that inhibited the
production of the Abeta42 peptide and to a lesser degree the Abeta40 peptide
while concomitantly increasing the production of the carboxyl-truncated Abeta38
and Abeta37 peptides. These modulators potently lower Abeta42 levels without
inhibiting the gamma-secretase-mediated proteolysis of Notch or causing
accumulation of carboxyl-terminal fragments of APP. In this study, we report a
large number of pharmacological studies and early assessment of toxicology
characterizing a highly potent gamma-secretase modulator (GSM), (S)-N-(1-(4
fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4
methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to
significantly lower Abeta42 levels in the central nervous system of rats and mice
at doses as low as 5-10 mg/kg, significantly reduce Abeta neuritic plaque load in
an AD transgenic mouse model, and significantly reduce levels of insoluble
Abeta42 and pThr181 tau in a three-dimensional human neural cell culture model.
Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose
toxicity studies in nonhuman primates have designated this GSM for 28-day
Investigational New Drug-enabling good laboratory practice studies and positioned
it as a candidate for human clinical trials.
PMID- 28416570
TI - Taking health into account in all policies: raising and keeping health equity
high on the political agenda.
PMID- 28416571
TI - Negative wealth shock and short-term changes in depressive symptoms and
medication adherence among late middle-aged adults.
AB - BACKGROUND: Experiencing a negative wealth shock in late middle age may cause
high levels of stress and induce reductions in health-related consumption.
METHODS: We used data on late middle age individuals (51-64 years) from the
longitudinal US-based Health and Retirement Study (N=19 281) to examine the
relationship between negative wealth shock and short-term outcomes that serve as
markers of the pathways from wealth shock to health: elevated depressive
symptoms, as a marker of the stress pathway and cost-related medication non
adherence (CRN), as a marker of the consumption pathway. Negative wealth shock
was considered to be a loss of total net worth of 75% or more. RESULTS: Using a
nested cross-over approach-a within-person design among exposed individuals only
that adjusts by design for all time-invariant individual characteristics-we found
that negative wealth shock was significantly associated with increased odds of
elevated depressive symptoms (OR=1.50, CI 1.10 to 2.05), but was not
significantly associated with higher odds of CRN (OR=1.18, CI 0.76 to 1.82), even
after further adjustment for time-varying sociodemographic and health covariates.
CONCLUSIONS: Negative wealth shock during late middle age confers an increased
risk of elevated depressive symptoms, but does not change levels of CRN. Personal
and policy factors that may buffer the mental health risks of negative wealth
shock, such as social support and social welfare policy, should be considered.
PMID- 28416572
TI - Alternatives assessment: new ideas, frameworks and policies.
PMID- 28416573
TI - Changes in directly alcohol-attributable mortality during the great recession by
employment status in Spain: a population cohort of 22 million people.
AB - BACKGROUND: Macroeconomic fluctuations can impact differentially on alcohol
related problems across sociodemographic groups. We assess trend changes in
directly alcohol-attributable (DAA) mortality in the population aged 25-64 during
the post-2008 recession in Spain according to employment status and other
sociodemographic factors. METHODS: Nationwide cohort study covering 21.9 million
people living in Spain in 2001. People were classified by employment status and
other factors. The annual percentage change (APC) in mortality rates during 2002
2007 (precrisis) and 2008-2011 (crisis) was estimated by the Poisson regression.
The period effect size was then calculated as the difference between crisis and
precrisis APCs. RESULTS: The age-adjusted APCs in DAA mortality were 6.9% in 2002
2007 and 3.7% in 2008-2011 among employed people, and -4.3% and -0.4%,
respectively, among non-employed people. Statistically significant trend changes
in such mortality during the crisis were found, which were favourable in certain
employed subgroups (manual workers and employees aged 25-49), and unfavourable in
the total non-employed population and certain non-employed subgroups (men, non
married and especially medium/high-wealth people). The greatest unfavourable
change corresponded to non-employed people living in households of 72-104 m2 who
had 2 or more cars. Favourable changes were also found in the remaining employed
subgroups, especially women and non-married people, although they did not reach
statistical significance. CONCLUSIONS: Our findings suggest that the post-2008
Spanish crisis had a heterogeneous impact across sociodemographic subgroups on
DAA mortality, and that employment status seemed to have an important effect. The
impact was especially unfavourable on the non-employed, particularly those with
substantial material wealth.
PMID- 28416575
TI - Moving Closer To Victory.
PMID- 28416574
TI - A Glutamate-Substituted Mutant Mimics the Phosphorylated and Active Form of
Guanylyl Cyclase-A.
AB - Multisite phosphorylation is required for activation of guanylyl cyclase (GC)-A,
also known as NPR-A or NPR1, by cardiac natriuretic peptides (NPs). Seven
chemically identified sites (Ser-487, Ser-497, Thr-500, Ser-502, Ser-506, Ser
510, and Thr-513) and one functionally identified putative site (Ser-473) were
reported. Single alanine substitutions for Ser-497, Thr-500, Ser-502, Ser-506,
and Ser-510 reduced maximal velocity (Vmax), whereas glutamate substitutions had
no effect or increased Vmax Ala but not Glu substitution for Ser-497 increased
the Michaelis constant (Km) approximately 400%. A GC-A mutant containing Glu
substitutions for all seven chemically identified sites (GC-A-7E) had a Km
approximately 10-fold higher than phosphorylated wild-type (WT) GC-A, but one
additional substitution for Ser-473 to make GC-A-8E resulted in the same Vmax,
Km, and EC50 as the phosphorylated WT enzyme. Adding more glutamates to make GC-A
9E or GC-A-10E had little effect on activity, and sequential deletion of
individual glutamates in GC-A-8E progressively increased the Km Double Ala
substitutions for Ser-497 and either Thr-500, Ser-510 or Thr-513 in WT-GC-A
increased the Km 23- to 70-fold but the same mutations in GC-A-8E only increased
the Km 8-fold, consistent with one site affecting the phosphorylation of other
sites. Phosphate measurements confirmed that single-site Ala substitutions
reduced receptor phosphate levels more than expected for the loss of a single
site. We conclude that a concentrated region of negative charge, not steric
properties, resulting from multiple interdependent phosphorylation sites is
required for a GC-A conformation capable of transmitting the hormone binding
signal to the catalytic domain.
PMID- 28416576
TI - Pathways Involved in Formation of Mammary Organoid Architecture Have Keys to
Understanding Drug Resistance and to Discovery of Druggable Targets.
AB - Signals from the extracellular matrix (ECM) are received at the cell surface
receptor, transmitted to the cytoskeletons, and transferred to the nucleus and
chromatin for tissue- and context-specific gene expression. Cells, in return,
modulate the cell shape and ECM, allowing for the maintenance of tissue
homeostasis as well as for coevolution and adaptation to the environmental
signals. We postulated the existence of dynamic and reciprocal interactions
between the ECM and the nucleus more than three decades ago, but now these
pathways have been proven experimentally thanks to the advances in imaging and
cell/molecular biology techniques. In this review, we will introduce some of our
recent work that has validated the critical roles of the three-dimensional (3D)
tissue architecture in determining mammary biology, therapeutic response, and
druggable targets. We describe a novel screen based on reversion of the malignant
phenotype in 3D assays. We will also summarize our recent discoveries of the
integration of feedback signaling for mammary acinar formation and phenotypic
reversion of tumor cells in the LrECM. Lastly, we will introduce our exciting
discovery of the physical linkages between the cell surface and cytofibers within
a tunnel deep inside of the nucleus, enabling interaction with nuclear lamin and
SUN proteins.
PMID- 28416578
TI - WITHDRAWN: Quantitative mass spectrometry analysis of PD-L1 protein expression, N
glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma.
AB - This article has been withdrawn by the authors. We discovered an error after this
manuscript was published as a Paper in Press. Specifically, we learned that the
structures of glycans presented for the PD-L1 peptide were drawn and labeled
incorrectly. We wish to withdraw this article and submit a corrected version for
review.
PMID- 28416577
TI - Normal and Neoplastic Stem Cells.
AB - A stem cell is broadly defined as a cell that retains the capacity to self-renew,
a feature that confers the ability to continuously make identical daughter cells
or additional cells that will differentiate into downstream progeny. This highly
regulated genetic program to retain "stemness" is under active investigation.
Research in our laboratory has explored similarities and differences in
embryonic, tissue-specific, and neoplastic stem cells and their terminally
differentiated counterparts. In this review, we will focus on the contributions
of our laboratory, in particular on the studies that identified the mouse
hematopoietic stem cell (HSC) and the human leukemic stem cell. These studies
have led to significant improvements in both preclinical and clinical research,
including improved clinical bone marrow transplantation protocols, isolation of
nonleukemic HSCs, a cancer immunotherapy currently in clinical trials, and
development of a HSC reporter mouse. These studies and the current follow-up
research by us and others will continue to identify the properties, function, and
regulation of both normal and neoplastic stem cells.
PMID- 28416579
TI - Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of
phospholipids containing unsaturated long (>=C20)-acyl chains in macrophages.
AB - Acyl-CoA thioesterase 7 (ACOT7) is an intracellular enzyme that converts acyl
CoAs to FFAs. ACOT7 is induced by lipopolysaccharide (LPS); thus, we investigated
downstream effects of LPS-induced induction of ACOT7 and its role in inflammatory
settings in myeloid cells. Enzymatic thioesterase activity assays in WT and ACOT7
deficient macrophage lysates indicated that endogenous ACOT7 contributes a
significant fraction of total acyl-CoA thioesterase activity toward C20:4-, C20:5
, and C22:6-CoA, but contributes little activity toward shorter acyl-CoA species.
Lipidomic analyses revealed that LPS causes a dramatic increase, primarily in
bis(monoacylglycero)phosphate species containing long (>=C20) polyunsaturated
acyl-chains in macrophages, and that the limited effect observed by ACOT7
deficiency is restricted to glycerophospholipids containing 20-carbon unsaturated
acyl-chains. Furthermore, ACOT7 deficiency did not detectably alter the ability
of LPS to induce cytokines or prostaglandin E2 production in macrophages.
Consistently, although ACOT7 was induced in macrophages from diabetic mice,
hematopoietic ACOT7 deficiency did not alter the stimulatory effect of diabetes
on systemic inflammation or atherosclerosis in LDL receptor-deficient mice. Thus,
inflammatory stimuli induce ACOT7 and remodeling of phospholipids containing
unsaturated long (>=C20)-acyl chains in macrophages, and, although ACOT7 has
preferential thioesterase activity toward these lipid species, loss of ACOT7 has
no major detrimental effect on macrophage inflammatory phenotypes.>=.
PMID- 28416580
TI - A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
AB - Intracerebral hemorrhage (ICH) is a devastating disease without effective
treatment. After ICH, the immediate infiltration of leukocytes and activation of
microglia are accompanied by a rapid up-regulation of the 18-kDa translocator
protein (TSPO). TSPO ligands have shown anti-inflammatory and neuroprotective
properties in models of CNS injury. In this study, we determined the impact of a
TSPO ligand, etifoxine, on brain injury and inflammation in 2 mouse models of
ICH. TSPO was up-regulated in Iba1+ cells from brains of patients with ICH and in
CD11b+CD45int cells from mice subjected to collagenase-induced ICH. Etifoxine
significantly reduced neurodeficits and perihematomal brain edema after ICH
induction by injection of either autologous blood or collagenase. In collagenase
induced ICH mice, the protection of etifoxine was associated with reduced
leukocyte infiltration into the brain and microglial production of IL-6 and TNF
alpha. Etifoxine improved blood-brain barrier integrity and diminished cell
death. Notably, the protective effect of etifoxine was abolished in mice depleted
of microglia by using a colony-stimulating factor 1 receptor inhibitor. These
results indicate that the TSPO ligand etifoxine attenuates brain injury and
inflammation after ICH. TSPO may be a viable therapeutic target that requires
further investigations in ICH.-Li, M., Ren, H., Sheth, K. N., Shi, F.-D., Liu, Q.
A TSPO ligand attenuates brain injury after intracerebral hemorrhage.
PMID- 28416582
TI - Relationship between oxygen concentration and temperature in an exothermic
warming device.
AB - INTRODUCTION: Actively warming hypothermic patients or preventing hypothermia is
critical in optimising outcomes in patients with traumatic injuries. Our aim was
to investigate the effect of ambient oxygen concentration on the rate and change
in temperature of the TechTrade Ready-Heat II exothermic (oxygen-activated)
warming blanket, to evaluate safety and ascertain the risk of thermal injury.
METHODS: A mannequin covered with an exothermic blanket was placed in a sealed
oxygen tent. An ambulance blanket was placed between the TechTrade Ready-Heat II
exothermic blanket and the mannequin. Two temperature probes were placed directly
on the surface of the mannequin; one on the torso away from the heating packs and
the other directly beneath the exothermic heating pack. The mannequin was exposed
to increasing oxygen concentrations at 10% increments, starting at 21%. The
experiment was conducted nine times, each time using a new blanket. Maximum
temperature of the mannequin 'skin' and rate of rise were recorded from both
temperature sensors. RESULTS: In room air (21% oxygen), the mannequin surface
reached 52 degrees C after 60 min, matching manufacturer specifications. At 30%
oxygen concentration, the temperature directly beneath the exothermic heating
pack exceeded the 65 degrees C threshold at which rapid thermal burns occur,
reaching 72.5 degrees C, with minimal change in overall torso temperature.
CONCLUSION: The supplemental use of oxygen in patients with traumatic injuries
that increases ambient oxygen levels in the presence of exothermic warming
devices may represent a significant risk to the patient. We suggest that
prehospital care providers remain highly vigilant of heat when using high-flow
oxygen and the subsequent fire risk, while manufacturers of exothermic blankets
should consider ways to improve safety.
PMID- 28416581
TI - TRP channels in brown and white adipogenesis from human progenitors: new
therapeutic targets and the caveats associated with the common antibiotic,
streptomycin.
AB - Transient receptor potential (TRP) channels are polymodal cell sensors responding
to diverse stimuli and widely implicated in the developmental programs of
numerous tissues. The evidence for an involvement of TRP family members in
adipogenesis, however, is scant. We present the first comprehensive expression
profile of all known 27 human TRP genes in mesenchymal progenitors cells during
white or brown adipogenesis. Using positive trilineage differentiation as an
exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to
be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the
brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator
activated receptor gamma coactivator (PGC)-1alpha as well as attenuated forskolin
stimulated uncoupled respiration. However, indices of generalized adipogenesis,
such as lipid droplet morphology and fatty acid binding protein (FAPB)-4
expression, were not affected, indicating a principal mitochondrial role of
TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression
and augmented uncoupled respiration predominantly in white adipocytes (browning),
whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP
1 expression, and mitigated uncoupled respiration; menthol was less capable of
augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and
TRPM8 hence appear to be involved in the priming of mitochondria to perform
uncoupled respiration downstream of adenylate cyclase. Our results also
underscore the developmental caveats of using antibiotics in adipogenic studies.
Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A.,
Shabbir, A., Franco-Obregon, A., Raghunath, M. TRP channels in brown and white
adipogenesis from human progenitors: new therapeutic targets and the caveats
associated with the common antibiotic, streptomycin.
PMID- 28416583
TI - Physiological and Pathological Roles in Human Adrenal of the Glomeruli-Defining
Matrix Protein NPNT (Nephronectin).
AB - Primary aldosteronism is a common cause of hypertension, which becomes refractory
if undiagnosed, but potentially curable when caused by an aldosterone-producing
adenoma (APA). The discovery of somatic mutations and differences in clinical
presentations led to recognition of small but common zona glomerulosa (ZG)-like
adenomas, distinct from classical large zona fasciculata-like adenomas. The
inverse correlation between APA size and aldosterone synthase expression prompted
us to undertake a systematic study of genotype-phenotype relationships. After a
microarray comparing tumor subtypes, in which NPNT (nephronectin) was the most
highly (>12-fold) upregulated gene in ZG-like APAs, we aimed to determine its
role in physiological and pathological aldosterone production. NPNT was
identified by immunohistochemistry as a secreted matrix protein expressed
exclusively around aldosterone-producing glomeruli in normal adrenal ZG and in
aldosterone-dense ZG-like APAs; the highest expression was in ZG-like APAs with
gain-of-function CTNNB1 mutations, whose removal cured hypertension in our
patients. NPNT was absent from normal zona fasciculata, zona fasciculata-like
APAs, and ZG adjacent to an APA. NPNT production was regulated by canonical Wnt
pathway, and NPNT overexpression or silencing increased or reduced aldosterone,
respectively. NPNT was proadhesive in primary adrenal and APA cells but
antiadhesive and antiapoptotic in immortalized adrenocortical cells. The
discovery of NPNT in the adrenal helped recognition of a common subtype of APAs
and a pathway by which Wnt regulates aldosterone production. We propose that this
arises through NPNT's binding to cell-surface integrins, stimulating cell-cell
contact within glomeruli, which define ZG. Therefore, NPNT or its cognate
integrin could present a novel therapeutic target.
PMID- 28416585
TI - Case of Refractory Hypertension Controlled by Repeated Renal Denervation and
Celiac Plexus Block: A Case of Refractory Sympathetic Overload.
PMID- 28416586
TI - 2-Methoxyestradiol: A 17beta-Estradiol Metabolite With Gender-Independent
Therapeutic Potential.
PMID- 28416584
TI - 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal
Dysfunction in Ovariectomized Female and Intact Male Mice.
AB - Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension
and associated cardiovascular changes in female mice, most likely via production
of 2-methoxyestradiol. This study was conducted to determine whether 2
methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and
end-organ damage in intact Cyp1b1-/-, ovariectomized female, and Cyp1b1+/+ male
mice. Ang II or vehicle was infused for 2 weeks and administered concurrently
with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II
infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II
induced increases in systolic blood pressure, water consumption, urine output,
and proteinuria in intact female Cyp1b1-/- and ovariectomized mice. 2
Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water
intake, urine output, and proteinuria in Cyp1b1+/+ male mice. Treatment with 2
methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1-/-
and ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice and Cyp1b1+/+ male mice. 2
Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of
angiotensinogen in intact Cyp1b1-/- and ovariectomized Cyp1b1+/+ and Cyp1b1-/-
female mice but not in Cyp1b1+/+ male mice. The G protein-coupled estrogen
receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood
pressure and renal function in Cyp1b1+/+ female mice. These data suggest that 2
methoxyestradiol reduces Ang II-induced hypertension and associated end-organ
damage in intact Cyp1b1-/-, ovariectomized Cyp1b1+/+ and Cyp1b1-/- female mice,
and Cyp1b1+/+ male mice independent of G protein-coupled estrogen receptor 1.
Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating
hypertension and associated pathogenesis in postmenopausal females, and in males.
PMID- 28416587
TI - Cardiovascular outcomes with an inhaled beta2-agonist/corticosteroid in patients
with COPD at high cardiovascular risk.
AB - OBJECTIVES: Cardiovascular disease (CVD) and chronic obstructive pulmonary
disease (COPD) often coexist. We assessed the effect of inhaled COPD treatments
on CVD outcomes and safety in patients with COPD and at heightened CVD risk.
METHODS: The SUMMIT (Study to Understand Mortality and MorbidITy) was a
multicentre, randomised, double-blind, placebo-controlled, event-driven trial in
16 485 patients with moderate COPD who had or were at high risk of CVD. Here, we
assessed the prespecified secondary endpoint of time to first on-treatment
composite CVD event (CVD death, myocardial infarction, stroke, unstable angina or
transient ischaemic attack (TIA)) by Cox regression and by clinician-reported CVD
adverse events across the four groups: once-daily inhaled placebo (n=4111), long
acting beta2-agonist (vilanterol (VI) 25 ug; n=4118), corticosteroid (fluticasone
furoate (FF) 100 ug; n=4135) and combination therapy (FF/VI; n=4121). RESULTS:
Participants were predominantly middle-aged (mean 65 (SD 8) years) men (75%) with
overt CVD (66%). The composite CVD endpoint occurred in 688 patients (first
event: sudden death (35%), acute coronary syndrome (37%) and stroke or TIA (23%),
and was not reduced in any treatment group versus placebo: VI (HR 0.99, 95% CI
0.80 to 1.22), FF (HR 0.90, 95% CI 0.72 to 1.11) and their combination (HR 0.93,
95% CI 0.75 to 1.14). Outcomes were similar among all subgroups. Adverse events,
including palpitations and arrhythmias, did not differ by treatment. CONCLUSIONS:
In patients with COPD with moderate airflow limitation and heightened CVD risk,
treatment with inhaled VI, FF or their combination has an excellent safety
profile and does not impact CVD outcomes. TRIAL REGISTRATION NUMBER: NCT01313676.
PMID- 28416588
TI - Association between mutation status and left ventricular reverse remodelling in
dilated cardiomyopathy.
AB - OBJECTIVE: To explore the genetic landscape of a well selected dilated
cardiomyopathy (DCM) cohort, assessing the possible relation between different
genotypes and left ventricular reverse remodelling (LVRR). METHODS: A cohort of
152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been
studied by next-generation sequencing (NGS). Patients were grouped into different
'gene-clusters' with functionally homogeneous genetic backgrounds. LVRR was
defined by left ventricular ejection fraction normalisation or increase >=10%
associated with normalisation in indexed left ventricular end-diastolic diameter
or relative decrease >=10% at 24 months follow-up. RESULTS: A pathogenic disease
related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%)
LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18
(12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features
were similar throughout the different genotypes. A significant relationship was
found between gene cluster subgroups and LVRR, with a lower rate of LVRR in
structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05
vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare
variants were independently and inversely associated with LVRR when adjusted for
clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011).
CONCLUSIONS: NGS confirmed a high genetic diagnostic yield in DCM. A specific
'gene-clusters' classification based on functional similarities in different
genes might be helpful in the clinical management of genetically determined DCM.
In this study, structural cytoskeleton Z-disk gene rare variants were
independently associated with a lower rate of LVRR at follow-up.
PMID- 28416589
TI - Multimodality imaging of the tricuspid valve with implication for percutaneous
repair approaches.
AB - Nowadays some percutaneous options for tricuspid valve (TV) repair are available:
Tricinch (4Tech Cardio, Galway, Ireland) mimicking the Kay procedure, Trialign
(Mitralign, Boston, MA, USA) aiming to bicuspidise TV, MitraClip (Abbott
Vascular, Abbott Park, Illinois, USA) mimicking Alfieri's stitch, direct
transcatheter annuloplasty with Cardioband (Valtech Cardio, Or Yehuda, Israel)
and transcatheter Forma Repair (Edwards Lifesciences, Irvine, California, USA)
providing a surface for leaflet coaptation. A multimodality imaging approach is
fundamental for defining the pathophysiology of tricuspid regurgitation (TR),
preprocedural planning and intraprocedural monitoring. Both 2-dimensional and 3
dimensional (3D) transthoracic echocardiography and transoesophageal
echocardiography (TOE) are essential for grading and anatomical characterisation
of TR, and evaluation of dimensions and function of right ventricle (RV) and
estimation of pulmonary pressure. In particular, 3D echocardiography provides a
better anatomical definition of TV apparatus and tricuspid annulus (TA) and
additional information about the anatomical relationships of TV and surrounding
structures. CT offers complementary information during the preprocedural planning
especially for procedures targeting TA such as annular structure and dimensions,
quality and amount of annular tissue and its relationship with the right coronary
artery, and the sizing of the inferior vena cava. Moreover, appropriate patient
selection is crucial. The best candidate seems to be a patient with functional TR
due to predominant annular dilatation with modest apical tethering, at least
partial preservation of leaflets coaptation, not severe pulmonary hypertension
and not advanced RV dilation and dysfunction. An example of intraprocedural
multimodality imaging approach with TOE, fluoroscopy, angiography and
intracardiac echocardiography is also reported.
PMID- 28416591
TI - Investigations for tuberculosis contacts: what are the real issues of all the
efforts?
PMID- 28416593
TI - Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and
Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small
GTPase.
AB - Multiple components have been identified that exhibit different stabilities for
aversive olfactory memory in Drosophila These components have been defined by
behavioral and genetic studies and genes specifically required for a specific
component have also been identified. Intermediate-term memory generated after
single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and
anesthesia-resistant memory (ARM), with the latter being more stable. We
determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and
that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas
the full-length form was required for ARM formation. Rgk1 is specifically
accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons
of the mushroom bodies, which play a pivotal role in olfactory memory formation.
A higher than normal Rgk1 level enhanced memory retention, which is consistent
with the result that Rgk1 suppressed Rac-dependent memory decay; these findings
suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that
Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as
a molecular node that resides at KC synapses, where the ASM and ARM pathway may
interact.SIGNIFICANCE STATEMENT Memory consists of multiple components.
Drosophila olfactory memory serves as a fundamental model with which to
investigate the mechanisms that underlie memory formation and has provided
genetic and molecular means to identify the components of memory, namely short
term, intermediate-term, and long-term memory, depending on how long the memory
lasts. Intermediate memory is further divided into anesthesia-sensitive memory
(ASM) and anesthesia-resistant memory (ARM), with the latter being more stable.
We have identified a small GTPase in Drosophila, Rgk1, which plays a pivotal role
in the regulation of olfactory memory stability. Rgk1 is required for both ASM
and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM
formation, whereas the full-length form was required for ARM formation.
PMID- 28416592
TI - 'WNT-er is coming': WNT signalling in chronic lung diseases.
AB - Chronic lung diseases represent a major public health problem with only limited
therapeutic options. An important unmet need is to identify compounds and drugs
that target key molecular pathways involved in the pathogenesis of chronic lung
diseases. Over the last decade, there has been extensive interest in
investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal
alterations have been linked to pulmonary disease pathogenesis and progression.
Here, we comprehensively review the cumulative evidence for WNT pathway
alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis,
pulmonary arterial hypertension, asthma and COPD. While many studies have focused
on the canonical WNT/beta-catenin signalling pathway, recent reports highlight
that non-canonical WNT signalling may also significantly contribute to chronic
lung pathologies; these studies will be particularly featured in this review. We
further discuss recent advances uncovering the role of WNT signalling early in
life, the potential of pharmaceutically modulating WNT signalling pathways and
highlight (pre)clinical studies describing promising new therapies for chronic
lung diseases.
PMID- 28416594
TI - New Repeat Polymorphism in the AKT1 Gene Predicts Striatal Dopamine D2/D3
Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human
Brain.
AB - The role of the protein kinase Akt1 in dopamine neurotransmission is well
recognized and has been implicated in schizophrenia and psychosis. However, the
extent to which variants in the AKT1 gene influence dopamine neurotransmission is
not well understood. Here we investigated the effect of a newly characterized
variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L-
(eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2)
availability and on dopamine release in healthy volunteers. We used PET and
[11C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of
these participants, we also measured intravenous methylphenidate-induced dopamine
release to measure dopamine release. Dopamine release was quantified as the
difference in specific binding of [11C]raclopride (nondisplaceable binding
potential) between baseline values and values following methylphenidate
injection. There was an effect of AKT1 genotype on DRD2 availability at baseline
for the caudate (F(2,90) = 8.2, p = 0.001) and putamen (F(2,90) = 6.6, p =
0.002), but not the ventral striatum (p = 0.3). For the caudate and putamen, LL
showed higher DRD2 availability than HH; HL were in between. There was also a
significant effect of AKT1 genotype on dopamine increases in the ventral striatum
(F(2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL.
However, no dopamine increases were observed in the caudate (p = 0.1) or putamen
(p = 0.8) following methylphenidate injection. Our results provide evidence that
the AKT1 gene modulates both striatal DRD2 availability and dopamine release in
the human brain, which could account for its association with schizophrenia and
psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits
investigation.SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in
schizophrenia and psychosis. This association is likely to reflect modulation of
dopamine signaling by Akt1 kinase since striatal dopamine hyperstimulation is
associated with psychosis and schizophrenia. Here, using PET with
[11C]raclopride, we identified in the AKT1 gene a new variable number tandem
repeat (VNTR) marker associated with baseline striatal dopamine D2/D3 receptor
availability and with methylphenidate-induced striatal dopamine increases in
healthy volunteers. Our results confirm the involvement of the AKT1 gene in
modulating striatal dopamine signaling in the human brain. Future studies are
needed to assess the association of this new VNTR AKT1 variant in schizophrenia
and drug-induced psychoses.
PMID- 28416595
TI - Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson's
Disease.
AB - Oscillations in neural activity play a critical role in neural computation and
communication. There is intriguing new evidence that the nonsinusoidal features
of the oscillatory waveforms may inform underlying physiological and
pathophysiological characteristics. Time-domain waveform analysis approaches
stand in contrast to traditional Fourier-based methods, which alter or destroy
subtle waveform features. Recently, it has been shown that the waveform features
of oscillatory beta (13-30 Hz) events, a prominent motor cortical oscillation,
may reflect near-synchronous excitatory synaptic inputs onto cortical pyramidal
neurons. Here we analyze data from invasive human primary motor cortex (M1)
recordings from patients with Parkinson's disease (PD) implanted with a deep
brain stimulator (DBS) to test the hypothesis that the beta waveform becomes less
sharp with DBS, suggesting that M1 input synchrony may be decreased. We find
that, in PD, M1 beta oscillations have sharp, asymmetric, nonsinusoidal features,
specifically asymmetries in the ratio between the sharpness of the beta peaks
compared with the troughs. This waveform feature is nearly perfectly correlated
with beta-high gamma phase-amplitude coupling (r = 0.94), a neural index
previously shown to track PD-related motor deficit. Our results suggest that the
pathophysiological beta generator is altered by DBS, smoothing out the beta
waveform. This has implications not only for the interpretation of the
physiological mechanism by which DBS reduces PD-related motor symptoms, but more
broadly for our analytic toolkit in general. That is, the often-overlooked time
domain features of oscillatory waveforms may carry critical physiological
information about neural processes and dynamics.SIGNIFICANCE STATEMENT To better
understand the neural basis of cognition and disease, we need to understand how
groups of neurons interact to communicate with one another. For example, there is
evidence that parkinsonian bradykinesia and rigidity may arise from an
oversynchronization of afferents to the motor cortex, and that these symptoms are
treatable using deep brain stimulation. Here we show that the waveform shape of
beta (13-30 Hz) oscillations, which may reflect input synchrony onto the cortex,
is altered by deep brain stimulation. This suggests that mechanistic inferences
regarding physiological and pathophysiological neural communication may be made
from the temporal dynamics of oscillatory waveform shape.
PMID- 28416597
TI - Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape
Encoding.
AB - In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells
contribute to visual object recognition. They receive concurrent inputs from
visual areas V4, V3, and V2. We asked how these different anatomical pathways
shape PIT response properties by deactivating them while monitoring PIT activity
in two male macaques. We found that cooling of V4 or V2|3 did not lead to
consistent changes in population excitatory drive; however, population pattern
analyses showed that V4-based pathways were more important than V2|3-based
pathways. We did not find any image features that predicted decoding accuracy
differences between both interventions. Using the HMAX hierarchical model of
visual recognition, we found that different groups of simulated "PIT" units with
different input histories (lacking "V2|3" or "V4" input) allowed for comparable
levels of object-decoding performance and that removing a large fraction of "PIT"
activity resulted in similar drops in performance as in the cooling experiments.
We conclude that distinct input pathways to PIT relay similar types of shape
information, with V1-dependent V4 cells providing more quantitatively useful
information for overall encoding than cells in V2 projecting directly to
PIT.SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of
the visual system, but most emphasize input transformations across a serial
hierarchy akin to the primary "ventral stream" (V1 -> V2 -> V4 -> IT). However,
the ventral stream also comprises parallel "bypass" pathways: V1 also connects to
V4, and V2 to IT. To explore the advantages of mixing long and short pathways in
the macaque brain, we used cortical cooling to silence inputs to posterior IT and
compared the findings with an HMAX model with parallel pathways.
PMID- 28416598
TI - EBV MicroRNA BART16 Suppresses Type I IFN Signaling.
AB - Type I IFNs play critical roles in orchestrating the antiviral defense by
inducing direct antiviral activities and shaping the adaptive immune response.
Viruses have evolved numerous strategies to specifically interfere with IFN
production or its downstream mediators, thereby allowing successful infection of
the host to occur. The prototypic human gammaherpesvirus EBV, which is associated
with infectious mononucleosis and malignant tumors, harbors many immune-evasion
proteins that manipulate the adaptive and innate immune systems. In addition to
proteins, the virus encodes >40 mature microRNAs for which the functions remain
largely unknown. In this article, we identify EBV-encoded miR-BART16 as a novel
viral immune-evasion factor that interferes with the type I IFN signaling
pathway. miR-BART16 directly targets CREB-binding protein, a key transcriptional
coactivator in IFN signaling, thereby inducing CREB-binding protein
downregulation in EBV-transformed B cells and gastric carcinoma cells. miR-BART16
abrogates the production of IFN-stimulated genes in response to IFN-alpha
stimulation and it inhibits the antiproliferative effect of IFN-alpha on latently
infected BL cells. By obstructing the type I IFN-induced antiviral response, miR
BART16 provides a means to facilitate the establishment of latent EBV infection
and enhance viral replication.
PMID- 28416596
TI - MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading
to fatally debilitating weakness. Because this disease predominantly affects MNs,
we aimed to characterize the distinct expression profile of that cell type to
elucidate underlying disease mechanisms and to identify novel targets that inform
on MN health during ALS disease time course. microRNAs (miRNAs) are short,
noncoding RNAs that can shape the expression profile of a cell and thus often
exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression,
we used Cre recombinase-dependent miRNA tagging and affinity purification in
mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes,
and microglia, we then focused on MN-enriched miRNAs via a comparative analysis
and found that they may functionally distinguish MNs postnatally from other
spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF
harvested from ALS models of MN disease demonstrated that one miRNA (miR-218)
tracked with MN loss and was responsive to an ALS therapy in rodent models.
Therefore, we have used cellular expression profiling tools to define the
distinct miRNA expression of MNs, which is likely to enrich future studies of MN
disease. This approach enabled the development of a novel, drug-responsive marker
of MN disease in ALS rodents.SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis
(ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain
and spinal cord are selectively lost. To develop tools to aid in our
understanding of the distinct expression profiles of MNs and, ultimately, to
monitor MN disease progression, we identified small regulatory microRNAs (miRNAs)
that were highly enriched or exclusive in MNs. The signal for one of these MN
enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where
its levels change as disease progresses, suggesting that it may be a clinically
useful marker of disease status. Furthermore, rats treated with ALS therapy have
restored expression of this MN RNA marker, making it an MN-specific and drug
responsive marker for ALS rodents.
PMID- 28416599
TI - Characterization of T-Dependent and T-Independent B Cell Responses to a Virus
like Particle.
AB - Natural pathogens, such as viruses, often induce T-dependent and T-independent Ab
responses. However, the activation and differentiation of Ag-specific B cells
under these conditions had not been examined in detail. In this study, we used
bacterial phage Qbeta-derived virus-like particles (Qbeta-VLPs) as an immunogen
to examine the T-independent and T-dependent phases of the response in mice.
Using Qbeta-specific cell labeling and enrichment methods developed in this
study, we were able to characterize the rare Ag-specific B cells in detail.
Surprisingly, we found that Qbeta-VLPs could induce Bcl-6 expression in
pregerminal center B cells independently of T cell help. In addition, Qbeta-VLP
induced T-independent responses could lead to isotype-switched and somatically
mutated memory B cells. Finally, in contrast to what has been reported with
several other Ags, long-lived IgG+ memory cells were induced by Qbeta-VLPs, with
IgM+ memory B cells being produced but only evident for a limited time,
suggesting that different types of immunogens may preferentially generate or
maintain IgM+ versus IgG+ memory B cells.
PMID- 28416600
TI - Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine:
Implications for Vaccine Design.
AB - RNA-based vaccines have recently emerged as a promising alternative to the use of
DNA-based and viral vector vaccines, in part because of the potential to simplify
how vaccines are made and facilitate a rapid response to newly emerging
infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM)
replicons encoding an Ag, and formulated with a synthetic delivery system, and
they induce broad-based immune responses in preclinical animal models. In our
study, in vivo imaging shows that after the immunization, SAM Ag expression has
an initial gradual increase. Gene expression profiling in injection-site tissues
from mice immunized with SAM-based vaccine revealed an early and robust induction
of type I IFN and IFN-stimulated responses at the site of injection, concurrent
with the preliminary reduced SAM Ag expression. This SAM vaccine-induced type I
IFN response has the potential to provide an adjuvant effect on vaccine potency,
or, conversely, it might establish a temporary state that limits the initial SAM
encoded Ag expression. To determine the role of the early type I IFN response,
SAM vaccines were evaluated in IFN receptor knockout mice. Our data indicate that
minimizing the early type I IFN responses may be a useful strategy to increase
primary SAM expression and the resulting vaccine potency. RNA sequence
modification, delivery optimization, or concurrent use of appropriate compounds
might be some of the strategies to finalize this aim.
PMID- 28416601
TI - CSReport: A New Computational Tool Designed for Automatic Analysis of Class
Switch Recombination Junctions Sequenced by High-Throughput Sequencing.
AB - B cells ensure humoral immune responses due to the production of Ag-specific
memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag
driven B cell activation induces terminal maturation and Ig isotype class switch
(class switch recombination [CSR]). CSR creates a virtually unique IgH locus in
every B cell clone by intrachromosomal recombination between two switch (S)
regions upstream of each C region gene. Amount and structural features of CSR
junctions reveal valuable information about the CSR mechanism, and analysis of
CSR junctions is useful in basic and clinical research studies of B cell
functions. To provide an automated tool able to analyze large data sets of CSR
junction sequences produced by high-throughput sequencing (HTS), we designed
CSReport, a software program dedicated to support analysis of CSR recombination
junctions sequenced with a HTS-based protocol (Ion Torrent technology). CSReport
was assessed using simulated data sets of CSR junctions and then used for
analysis of SMU-Salpha and SMU-Sgamma1 junctions from CH12F3 cells and primary
murine B cells, respectively. CSReport identifies junction segment breakpoints on
reference sequences and junction structure (blunt-ended junctions or junctions
with insertions or microhomology). Besides the ability to analyze unprecedentedly
large libraries of junction sequences, CSReport will provide a unified framework
for CSR junction studies. Our results show that CSReport is an accurate tool for
analysis of sequences from our HTS-based protocol for CSR junctions, thereby
facilitating and accelerating their study.
PMID- 28416602
TI - Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and
Visualization of T and B Cell Receptor Repertoire Data.
AB - Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and
visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of
four parts: the demultiplex tool, the international ImMunoGeneTics information
system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic
hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they
allow the analysis of all different aspects of the immune repertoire. All
pipelines can be run independently or combined, depending on the available data
and the question of interest. The demultiplex tool allows data trimming and
demultiplexing, whereas with the concatenate tool multiple IMGT/HighV-QUEST
output files can be merged into a single file. The immune repertoire pipeline is
an extended version of our previously published ImmunoGlobulin Galaxy (IGGalaxy)
virtual machine that was developed to visualize V(D)J gene usage. It allows
analysis of both BCR and TCR rearrangements, visualizes CDR3 characteristics
(length and amino acid usage) and junction characteristics, and calculates the
diversity of the immune repertoire. Finally, ARGalaxy includes the newly
developed SHM and CSR pipeline to analyze SHM and/or CSR in BCR rearrangements.
It analyzes the frequency and patterns of SHM, Ag selection (including BASELINe),
clonality (Change-O), and CSR. The functionality of the ARGalaxy tool is
illustrated in several clinical examples of patients with primary
immunodeficiencies. In conclusion, ARGalaxy is a novel tool for the analysis of
the complete immune repertoire, which is applicable to many patient groups with
disturbances in the immune repertoire such as autoimmune diseases, allergy, and
leukemia, but it can also be used to address basic research questions in
repertoire formation and selection.
PMID- 28416603
TI - High-Throughput Immunogenetics for Clinical and Research Applications in
Immunohematology: Potential and Challenges.
AB - Analysis and interpretation of Ig and TCR gene rearrangements in the
conventional, low-throughput way have their limitations in terms of resolution,
coverage, and biases. With the advent of high-throughput, next-generation
sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene
rearrangements is now within reach, which impacts on all main applications of
IG/TR immunogenetic analysis. To bridge the generation gap from low- to high
throughput analysis, the EuroClonality-NGS Consortium has been formed, with the
main objectives to develop, standardize, and validate the entire workflow of
IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease
detection, and 3) repertoire analysis. This concerns the preanalytical (sample
preparation, target choice), analytical (amplification, NGS), and postanalytical
(immunoinformatics) phases. Here we critically discuss pitfalls and challenges of
IG/TR NGS methodology and its applications in hemato-oncology and immunology.
PMID- 28416604
TI - Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast
Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor
Erdafitinib.
AB - Fibroblast growth factor receptor (FGFR) genetic alterations are frequently
observed in cancer, suggesting that FGFR inhibition may be a promising therapy in
patients harboring these lesions. Identification of predictive and
pharmacodynamic biomarkers to select and monitor patients most likely to respond
to FGFR inhibition will be the key to clinical development of this class of
agents. Sensitivity to FGFR inhibition and correlation with FGFR pathway
activation status were determined in molecularly annotated panels of cancer cell
lines and xenograft models. Pathway inhibition in response to FGFR inhibitor
treatment was assessed in cell lines (both in vitro and in vivo) and in samples
from patients treated with the FGFR inhibitor JNJ-42756493 (erdafitinib).
Frequency of FGFR aberrations was assessed in a panel of NSCLC, breast, prostate,
ovarian, colorectal, and melanoma human tumor tissue samples. FGFR translocations
and gene amplifications present in clinical specimens were shown to display
potent transforming activity associated with constitutive pathway activation.
Tumor cells expressing these FGFR activating mutants displayed sensitivity to the
selective FGFR inhibitor erdafitinib and resulted in suppression of FGFR
phosphorylation and downstream signal transduction. Clinically, patients
receiving erdafitinib showed decreased Erk phosphorylation in tumor biopsies and
elevation of serum phosphate. In a phase I study, a heavily pretreated bladder
cancer patient with an FGFR3-TACC3 translocation experienced a partial response
when treated with erdafitinib. This preclinical study confirmed pharmacodynamics
and identified new predictive biomarkers to FGFR inhibition with erdafitinib and
supports further clinical evaluation of this compound in patients with FGFR
genetic alterations. Mol Cancer Ther; 16(8); 1717-26. (c)2017 AACR.
PMID- 28416605
TI - Photodynamic Therapy Using Photosensitizer-Encapsulated Polymeric Nanoparticle to
Overcome ATP-Binding Cassette Transporter Subfamily G2 Function in Pancreatic
Cancer.
AB - Chlorin-based photosensitizers are commonly used in photodynamic therapy (PDT).
These drugs are effluxed by cell membrane transporters, such as the ATP-binding
cassette subfamily G member 2 (ABCG2). PDT efficacy is limited in tumor cells
expressing high levels of these proteins. Pancreatic cancer cell lines AsPC-1 and
MIA PaCa-2, which have high and low ABCG2 expression, respectively, were used,
and ABCG2-overexpressing MIA PaCa-2 cells were generated. We compared PDT
efficacy between chlorin e6 (Ce6) and cationic photosensitizer-encapsulated
polymeric nanoparticle (PS-pNP), which is comprised with Ce6, polyethylene
glycol, and polyethylenimine. The intracellular concentration of Ce6 was
significantly higher in MIA PaCa-2 cells than in AsPC-1 or ABCG2-overexpressing
MIA PaCa-2 cells. PS-pNP increased intracellular levels of the photosensitizer in
all cell lines. The cell viability experiments indicated increased Ce6 resistance
in ABCG2-overexpressing cells. In contrast, PS-pNP produced similar levels of
cytotoxicity in each of the cancer cell lines tested. Singlet oxygen production
was higher in cells treated with PS-pNP than in those treated with Ce6.
Furthermore, in heterotopic and orthotopic AsPC-1 xenograft mouse models, PDT
using PS-pNP significantly reduced tumor volume in comparison with that of Ce6
treatment. PS-pNP could increase intracellular Ce6 concentration, which was
related with reduced ABCG2-mediated efflux of Ce6, thereby enhancing the effects
of PDT in pancreatic cancer cells. Mol Cancer Ther; 16(8); 1487-96. (c)2017 AACR.
PMID- 28416606
TI - TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative
Breast Cancers via Regulating Alternative Splicing.
AB - Treatment of triple-negative breast cancer (TNBC) has been challenging, and
paclitaxel resistance is one of the major obstacles to the better prognosis.
Deregulation of alternative splicing (AS) may contribute to tumor progression and
chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs
encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival
and therapeutic sensitivity. However, the individual role of TRA2A in cancer
progression has not been reported. Here we report that TRA2A facilitates
proliferation and survival and migration and invasion of TNBC cells. In addition,
TRA2A promotes paclitaxel resistance of TNBC by specifically controlling cancer
related splicing, which is independent of other splicing factors. TRA2A
overexpression could promote AS of CALU, RSRC2, and PALM during paclitaxel
treatment of TNBC cells. The isoform shift of RSRC2 from RSRC2s to RSRC2l leads
to a decreased RSRC2 protein expression, which could contribute to TNBC
paclitaxel resistance. TRA2A can regulate RSRC2 AS by specifically binding
upstream intronic sequence of exon4. Strikingly, TRA2A expression is increased
dramatically in patients with TNBC, and has a close relationship with decreased
RSRC2 expression; both are associated with poor survival of TNBC. Collectively,
our findings suggest that paclitaxel targets the TRA2A-RSRC2 splicing pathway,
and deregulated TRA2A and RSRC2 expression may confer paclitaxel resistance. In
addition to providing a novel molecular mechanism of cancer-related splicing
dysregulation, our study demonstrates that expression of TRA2A in conjunction
with RSRC2 may provide valuable molecular biomarker evidence for TNBC clinical
treatment decisions and patient outcome. Mol Cancer Ther; 16(7); 1377-88. (c)2017
AACR.
PMID- 28416607
TI - Human milk oligosaccharides inhibit growth of group B Streptococcus.
AB - Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of
invasive bacterial infections in newborns, typically acquired vertically during
childbirth secondary to maternal vaginal colonization. Human milk
oligosaccharides (HMOs) have important nutritional and biological activities that
guide the development of the immune system of the infant and shape the
composition of normal gut microbiota. In this manner, HMOs help protect against
pathogen colonization and reduce the risk of infection. In the course of our
studies of HMO-microbial interactions, we unexpectedly uncovered a novel HMO
property to directly inhibit the growth of GBS independent of host immunity. By
separating different HMO fractions through multidimensional chromatography, we
found the bacteriostatic activity to be confined to specific non-sialylated HMOs
and synergistic with a number of conventional antibiotic agents. Phenotypic
screening of a GBS transposon insertion library identified a mutation within a
GBS-specific gene encoding a putative glycosyltransferase that confers resistance
to HMOs, suggesting that HMOs may function as an alternative substrate to modify
a GBS component in a manner that impairs growth kinetics. Our study uncovers a
unique antibacterial role for HMOs against a leading neonatal pathogen and
expands the potential therapeutic utility of these versatile molecules.
PMID- 28416608
TI - Hyper-O-GlcNAcylation activates nuclear factor kappa-light-chain-enhancer of
activated B cells (NF-kappaB) signaling through interplay with phosphorylation
and acetylation.
AB - O-GlcNAcylation is the covalent addition of an O-linked beta-N-acetylglucosamine
(O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of
cytosolic and nuclear proteins. O-GlcNAcylation, analogous to phosphorylation,
plays critical roles in gene expression through direct modification of
transcription factors, such as NF-kappaB. Aberrantly increased NF-kappaB O
GlcNAcylation has been linked to NF-kappaB constitutive activation and cancer
development. Therefore, it is of a great biological and clinical significance to
dissect the molecular mechanisms that tune NF-kappaB activity. Recently, we and
others have shown that O-GlcNAcylation affects the phosphorylation and
acetylation of NF-kappaB subunit p65/RelA. However, the mechanism of how O
GlcNAcylation activates NF-kappaB signaling through phosphorylation and
acetylation is not fully understood. In this study, we mapped O-GlcNAcylation
sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. O-GlcNAcylation
of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent
activating acetylation of p65 at Lys-310, contributing to NF-kappaB
transcriptional activation. Moreover, elevation of O-GlcNAcylation by
overexpression of OGT increased the expression of p300, IKKalpha, and IKKbeta and
promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing
to NF-kappaB activation. In addition, we also identified phosphorylation of p65
at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. These
results indicate mechanisms through which both non-pathological and oncogenic O
GlcNAcylation regulate NF-kappaB signaling through interplay with phosphorylation
and acetylation.
PMID- 28416609
TI - CD36 receptor regulates malaria-induced immune responses primarily at early blood
stage infection contributing to parasitemia control and resistance to mortality.
AB - In malaria, CD36 plays several roles, including mediating parasite sequestration
to host organs, phagocytic clearance of parasites, and regulation of immunity.
Although the functions of CD36 in parasite sequestration and phagocytosis have
been clearly defined, less is known about its role in malaria immunity. Here, to
understand the function of CD36 in malaria immunity, we studied parasite growth,
innate and adaptive immune responses, and host survival in WT and Cd36-/- mice
infected with a non-lethal strain of Plasmodium yoelii Compared with Cd36-/-
mice, WT mice had lower parasitemias and were resistant to death. At early but
not at later stages of infection, WT mice had higher circulatory proinflammatory
cytokines and lower anti-inflammatory cytokines than Cd36-/- mice. WT mice showed
higher frequencies of proinflammatory cytokine-producing and lower frequencies of
anti-inflammatory cytokine-producing dendritic cells (DCs) and natural killer
cells than Cd36-/- mice. Cytokines produced by co-cultures of DCs from infected
mice and ovalbumin-specific, MHC class II-restricted alpha/beta (OT-II) T cells
reflected CD36-dependent DC function. WT mice also showed increased Th1 and
reduced Th2 responses compared with Cd36-/- mice, mainly at early stages of
infection. Furthermore, in infected WT mice, macrophages and neutrophils
expressed higher levels of phagocytic receptors and showed enhanced phagocytosis
of parasite-infected erythrocytes than those in Cd36-/- mice in an IFN-gamma
dependent manner. However, there were no differences in malaria-induced humoral
responses between WT and Cd36-/- mice. Overall, the results show that CD36 plays
a significant role in controlling parasite burden by contributing to
proinflammatory cytokine responses by DCs and natural killer cells, Th1
development, phagocytic receptor expression, and phagocytic activity.
PMID- 28416610
TI - Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels
in human platelets and a megakaryocytic cell line.
AB - The role of mechanosensitive (MS) Ca2+-permeable ion channels in platelets is
unclear, despite the importance of shear stress in platelet function and life
threatening thrombus formation. We therefore sought to investigate the expression
and functional relevance of MS channels in human platelets. The effect of shear
stress on Ca2+ entry in human platelets and Meg-01 megakaryocytic cells loaded
with Fluo-3 was examined by confocal microscopy. Cells were attached to glass
coverslips within flow chambers that allowed applications of physiological and
pathological shear stress. Arterial shear (1002.6 s-1) induced a sustained
increase in [Ca2+] i in Meg-01 cells and enhanced the frequency of repetitive
Ca2+ transients by 80% in platelets. These Ca2+ increases were abrogated by the
MS channel inhibitor Grammostola spatulata mechanotoxin 4 (GsMTx-4) or by
chelation of extracellular Ca2+ Thrombus formation was studied on collagen-coated
surfaces using DiOC6-stained platelets. In addition, [Ca2+] i and functional
responses of washed platelet suspensions were studied with Fura-2 and light
transmission aggregometry, respectively. Thrombus size was reduced 50% by GsMTx
4, independently of P2X1 receptors. In contrast, GsMTx-4 had no effect on
collagen-induced aggregation or on Ca2+ influx via TRPC6 or Orai1 channels and
caused only a minor inhibition of P2X1-dependent Ca2+ entry. The Piezo1 agonist,
Yoda1, potentiated shear-dependent platelet Ca2+ transients by 170%. Piezo1 mRNA
transcripts and protein were detected with quantitative RT-PCR and Western
blotting, respectively, in both platelets and Meg-01 cells. We conclude that
platelets and Meg-01 cells express the MS cation channel Piezo1, which may
contribute to Ca2+ entry and thrombus formation under arterial shear.
PMID- 28416611
TI - The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal
activities and ubiquitin-independent proteolysis.
AB - The proteasome-associated deubiquitinating enzyme Usp14/Ubp6 inhibits protein
degradation by catalyzing substrate deubiquitination and by poorly understood
allosteric actions. However, upon binding a ubiquitin chain, Usp14 enhances
proteasomal degradation by stimulating ATP and peptide degradation. These studies
were undertaken to clarify these seemingly opposite regulatory roles of Usp14 and
their importance. To learn how the presence of Usp14 on 26S proteasomes
influences its different activities, we compared enzymatic and regulatory
properties of 26S proteasomes purified from wild-type mouse embryonic fibroblast
cells and those lacking Usp14. The proteasomes lacking Usp14 had higher basal
peptidase activity than WT 26S, and this activity was stimulated to a greater
extent by adenosine 5'-O-(thiotriphosphate) (ATPgammaS) than with WT particles.
These differences were clear even though Usp14 is present on only a minor
fraction (30-40%) of the 26S in WT mouse embryonic fibroblast cells. Addition of
purified Usp14 to the WT and Usp14-defficient proteasomes reduced both their
basal peptidase activity and the stimulation by ATPgammaS. Usp14 inhibits these
processes allosterically because a catalytically inactive Usp14 mutant also
inhibited them. Proteasomes lacking Usp14 also exhibited greater deubiquitinating
activity by Rpn11 and greater basal ATPase activity than WT particles. ATP
hydrolysis by WT proteasomes is activated if they bind a ubiquitinated protein,
which is loosely folded. Surprisingly, proteasomes lacking Usp14 could be
activated by such proteins even without a ubiquitin chain present. Furthermore,
proteasomes lacking Usp14 are much more active in degrading non-ubiquitinated
proteins (e.g. Sic1) than WT particles. Thus, without a ubiquitinated substrate
present, Usp14 suppresses multiple proteasomal activities, especially basal ATP
consumption and degradation of non-ubiquitinated proteins. These allosteric
effects thus reduce ATP hydrolysis by inactive proteasomes and nonspecific
proteolysis and enhance proteasomal specificity for ubiquitinated proteins.
PMID- 28416612
TI - A biochemical and biophysical model of G-quadruplex DNA recognition by positive
coactivator of transcription 4.
AB - DNA sequences that are guanine-rich have received considerable attention because
of their potential to fold into a secondary, four-stranded DNA structure termed G
quadruplex (G4), which has been implicated in genomic instability and some human
diseases. We have previously identified positive coactivator of transcription
(PC4), a single-stranded DNA (ssDNA)-binding protein, as a novel G4 interactor.
Here, to expand on these previous observations, we biochemically and
biophysically characterized the interaction between PC4 and G4DNA. PC4 can bind
alternative G4DNA topologies with a low nanomolar Kd value of ~2 nm, similar to
that observed for ssDNA. In consideration of the different structural features
between G4DNA and ssDNA, these binding data indicated that PC4 can interact with
G4DNA in a manner distinct from ssDNA. The stoichiometry of the PC4-G4 complex
was 1:1 for PC4 dimer:G4 substrate. PC4 did not enhance the rate of folding of
G4DNA, and formation of the PC4-G4DNA complex did not result in unfolding of the
G4DNA structure. We assembled a G4DNA structure flanked by duplex DNA. We find
that PC4 can interact with this G4DNA, as well as the complementary C-rich
strand. Molecular docking simulations and DNA footprinting experiments suggest a
model where a PC4 dimer accommodates the DNA with one monomer on the G4 strand
and the second monomer bound to the C-rich strand. Collectively, these data
provide a novel mode of PC4 binding to a DNA secondary structure that remains
within the framework of the model for binding to ssDNA. Additionally,
consideration of the PC4-G4DNA interaction could provide insight into the
biological functions of PC4, which remain incompletely understood.
PMID- 28416615
TI - Spotlight on the April 18 issue.
PMID- 28416613
TI - Hypoxia-inducible factor 1alpha activates insulin-induced gene 2 (Insig-2)
transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase
in the liver.
AB - Cholesterol synthesis is a highly oxygen-consuming process. As such, oxygen
deprivation (hypoxia) limits cholesterol synthesis through incompletely
understood mechanisms mediated by the oxygen-sensitive transcription factor
hypoxia-inducible factor 1alpha (HIF-1alpha). We show here that HIF-1alpha links
pathways for oxygen sensing and feedback control of cholesterol synthesis in
human fibroblasts by directly activating transcription of the INSIG-2 gene. Insig
2 is one of two endoplasmic reticulum membrane proteins that inhibit cholesterol
synthesis by mediating sterol-induced ubiquitination and subsequent endoplasmic
reticulum-associated degradation of the rate-limiting enzyme in the pathway, HMG
CoA reductase (HMGCR). Consistent with the results in cultured cells, hepatic
levels of Insig-2 mRNA were enhanced in mouse models of hypoxia. Moreover,
pharmacologic stabilization of HIF-1alpha in the liver stimulated HMGCR
degradation via a reaction that requires the protein's prior ubiquitination and
the presence of the Insig-2 protein. In summary, our results show that HIF-1alpha
activates INSIG-2 transcription, leading to accumulation of Insig-2 protein,
which binds to HMGCR and triggers its accelerated ubiquitination and degradation.
These results indicate that HIF-mediated induction of Insig-2 and degradation of
HMGCR are physiologically relevant events that guard against wasteful oxygen
consumption and inappropriate cell growth during hypoxia.
PMID- 28416616
TI - Editors' Note.
PMID- 28416617
TI - Letter re: Cognitive reserve in frontotemporal degeneration: Neuroanatomic and
neuropsychological evidence.
PMID- 28416614
TI - Modeling Combined Immunosuppressive and Anti-inflammatory Effects of
Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of
Naproxen.
AB - Dexamethasone (DEX), a widely prescribed corticosteroid, has long been the
cornerstone of the treatment of inflammation and immunologic dysfunctions in
rheumatoid arthritis. Corticosteroids are frequently used in combination with
other antirheumatic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs)
and disease-modifying antirheumatic drugs to mitigate disease symptoms and
minimize unwanted effects. We explored the steroid dose-sparing potential of the
NSAID naproxen (NPX) with in vitro and in vivo studies. The single and joint
suppressive effects of DEX and NPX on the in vitro mitogen-induced proliferation
of T lymphocytes in blood and their anti-inflammatory actions on paw edema were
investigated in female and male Lewis rats with collagen-induced arthritis (CIA).
As expected, DEX was far more potent than NPX in these systems. Mathematical
models incorporating an interaction term psi were applied to quantitatively
assess the nature and intensity of pharmacodynamic interactions between DEX and
NPX. Modest synergistic effects of the two drugs were found in suppressing the
mitogenic response of T lymphocytes. A pharmacokinetic/pharmacodynamic/disease
progression model integrating dual drug inhibition quantitatively described the
pharmacokinetics, time-course of single and joint anti-inflammatory effects (paw
edema), and sex differences in CIA rats, and indicated additive effects of DEX
and NPX. Further model simulations demonstrated the promising steroid-sparing
potential of NPX in CIA rats, with the beneficial effects of the combination
therapy more likely in males than females.
PMID- 28416618
TI - Author response: Cognitive reserve in frontotemporal degeneration: Neuroanatomic
and neuropsychological evidence.
PMID- 28416619
TI - Letter re: Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416621
TI - Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416620
TI - Author response: Tuberculous optochiasmatic arachnoiditis and vision loss.
PMID- 28416622
TI - Clinical Reasoning: A child with delayed motor milestones and ptosis.
PMID- 28416623
TI - Teaching NeuroImages: Acute Parinaud syndrome.
PMID- 28416624
TI - Teaching Video NeuroImages: Maneuvers to elicit opsoclonus in opsoclonus
myoclonus syndrome.
PMID- 28416625
TI - Letter by Sposato et al Regarding Article, "Stroke as the Initial Manifestation
of Atrial Fibrillation: The Framingham Heart Study".
PMID- 28416627
TI - Response by Lubitz et al to Letter Regarding Article, "Stroke as the Initial
Manifestation of Atrial Fibrillation: The Framingham Heart Study".
PMID- 28416626
TI - Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND AND PURPOSE: The safety and efficacy of restarting anticoagulation
therapy after intracranial hemorrhage (ICH) remain unclear. We performed a
systematic review and meta-analysis to summarize the associations of
anticoagulation resumption with the subsequent risk of ICH recurrence and
thromboembolism. METHODS: We searched published medical literature to identify
cohort studies involving adults with anticoagulation-associated ICH. Our
predictor variable was resumption of anticoagulation. Outcome measures were
thromboembolic events (stroke and myocardial infarction) and recurrence of ICH.
After assessing study heterogeneity and publication bias, we performed a meta
analysis using random-effects models to assess the strength of association
between anticoagulation resumption and our outcomes. RESULTS: Eight studies were
eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all
studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of
anticoagulation was associated with a significantly lower risk of thromboembolic
complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45;
Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of
recurrent ICH after reinstatement of anticoagulation therapy, although there was
significant heterogeneity among included studies (pooled relative risk, 1.01; 95%
confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No
significant publication bias was detected in our analyses. CONCLUSIONS: In
observational studies, reinstitution of anticoagulation after ICH was associated
with a lower risk of thromboembolic complications and a similar risk of ICH
recurrence. Randomized clinical trials are needed to determine the true risk
benefit profile of anticoagulation resumption after ICH.
PMID- 28416628
TI - Impaired Glutamatergic Neurotransmission in the Ventromedial Hypothalamus May
Contribute to Defective Counterregulation in Recurrently Hypoglycemic Rats.
AB - The objectives of this study were to understand the role of glutamatergic
neurotransmission in the ventromedial hypothalamus (VMH) in response to
hypoglycemia and to elucidate the effects of recurrent hypoglycemia (RH) on this
neurotransmitter. We 1) measured changes in interstitial VMH glutamate levels by
using microdialysis and biosensors, 2) identified the receptors that mediate
glutamate's stimulatory effects on the counterregulatory responses, 3) quantified
glutamate metabolic enzyme levels in the VMH, 4) examined astrocytic glutamate
reuptake mechanisms, and 5) used 1H-[13C]-nuclear magnetic resonance (NMR)
spectroscopy to evaluate the effects of RH on neuronal glutamate metabolism. We
demonstrated that glutamate acts through kainic acid receptors in the VMH to
augment counterregulatory responses. Biosensors showed that the normal transient
rise in glutamate levels in response to hypoglycemia is absent in RH animals.
More importantly, RH reduced extracellular glutamate concentrations partly as a
result of decreased glutaminase expression. Decreased glutamate was also
associated with reduced astrocytic glutamate transport in the VMH. NMR analysis
revealed a decrease in [4-13C]glutamate but unaltered [4-13C]glutamine
concentrations in the VMH of RH animals. The data suggest that glutamate release
is important for proper activation of the counterregulatory response to
hypoglycemia and that impairment of glutamate metabolic and resynthetic pathways
with RH may contribute to counterregulatory failure.
PMID- 28416629
TI - Individual differences in fear extinction and anxiety-like behavior.
AB - There is growing appreciation for the substantial individual differences in the
acquisition and inhibition of aversive associations, and the insights this might
give into identifying individuals particularly vulnerable to stress and
psychopathology. We examined whether animals that differed in rate of extinction
(i.e., Fast versus Slow) were different in their response to an acute stress in
adulthood or following a chronic stress that occurred either early or later in
life. We found that Slow Extinguishers had significantly poorer extinction
retention than Fast Extinguishers, but an acute stressor did not differentially
affect anxiety-like behavior in the two groups. Further, while exposure to
chronic stress in adulthood did not impact on the extinction phenotypes or
anxiety-like behavior, exposure to chronic stress early in life affected both
extinction retention and anxiety-like behavior. These findings have implications
for the development of a more nuanced approach to identifying those most at risk
of anxiety disorders.
PMID- 28416630
TI - Common microbehavioral "footprint" of two distinct classes of conditioned
aversion.
AB - Avoiding unfavorable situations is a vital skill and a constant task for any
animal. Situations can be unfavorable because they feature something that the
animal wants to escape from, or because they do not feature something that it
seeks to obtain. We investigate whether the microbehavioral mechanisms by which
these two classes of aversion come about are shared or distinct. We find that
larval Drosophila avoid odors either previously associated with a punishment, or
previously associated with the lack of a reward. These two classes of conditioned
aversion are found to be strikingly alike at the microbehavioral level. In both
cases larvae show more head casts when oriented toward the odor source than when
oriented away, and direct fewer of their head casts toward the odor than away
when oriented obliquely to it. Thus, conditioned aversion serving two
qualitatively different functions-escape from a punishment or search for a reward
is implemented by the modulation of the same microbehavioral features. These
features also underlie conditioned approach, albeit with opposite sign. That is,
the larvae show conditioned approach toward odors previously associated with a
reward, or with the lack of a punishment. In order to accomplish both these
classes of conditioned approach the larvae show fewer head casts when oriented
toward an odor, and direct more of their head casts toward it when they are
headed obliquely. Given that the Drosophila larva is a genetically tractable
model organism that is well suited to study simple circuits at the single-cell
level, these analyses can guide future research into the neuronal circuits
underlying conditioned approach and aversion, and the computational principles of
conditioned search and escape.
PMID- 28416631
TI - Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of
plasticity and memory by manipulating actin remodeling.
AB - Recent human exome-sequencing studies have implicated polymorphic Brg1-associated
factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in
several intellectual disabilities and cognitive disorders, including autism.
However, it remains unclear how mutations in BAF complexes result in impaired
cognitive function. Post-mitotic neurons express a neuron-specific assembly,
nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b
is essential for the differentiation of neuronal precursor cells into neurons. We
generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bDeltaSB2). Long
term synaptic potentiation (LTP) and long-term memory, both of which are
associated with phosphorylation of the actin severing protein cofilin, were
assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically
delivered into the hippocampus of BAF53bDeltaSB2 mice in an effort to rescue LTP
and memory. BAF53bDeltaSB2 mutant mice show impairments in phosphorylation of
synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory
deficits are rescued by overexpression of a phosphorylation mimetic of cofilin.
Baseline physiology and behavior were not affected by the mutation or the
experimental treatment. This study suggests a potential link between nBAF
function, actin cytoskeletal remodeling at the dendritic spine, and memory
formation. This work shows that a targeted manipulation of synaptic function can
rescue adult plasticity and memory deficits caused by manipulations of nBAF, and
thereby provides potential novel avenues for therapeutic development for multiple
intellectual disability disorders.
PMID- 28416632
TI - Null EPAC mutants reveal a sequential order of versatile cAMP effects during
Drosophila aversive odor learning.
AB - Here, we define a role of the cAMP intermediate EPAC in Drosophila aversive odor
learning by means of null epac mutants. Complementation analysis revealed that
EPAC acts downstream from the rutabaga adenylyl cyclase and in parallel to
protein kinase A. By means of targeted knockdown and genetic rescue we identified
mushroom body Kenyon cells (KCs) as a necessary and sufficient site of EPAC
action. We provide mechanistic insights by analyzing acquisition dynamics and
using the "performance increment" as a means to access the trial-based sequential
organization of odor learning. Thereby we show that versatile cAMP-dependent
mechanisms are engaged within a sequential order that correlate to individual
trials of the training session.
PMID- 28416633
TI - Intrusions in episodic memory: reconsolidation or interference?
AB - It would be profoundly important if reconsolidation research in animals and other
memory domains generalized to human episodic memory. A 3-d-list-discrimination
procedure, based on free recall of objects, with a contextual reminder cue (the
testing room), has been thought to demonstrate reconsolidation of human episodic
memory (as noted in a previous study). Our goal was to replicate the central
result, a high intrusion rate during recall of the target list, and evaluate the
reconsolidation account relative to an alternative account, based on state
dependent learning and interference. First, replication was not straightforward
(Experiment 1). Second, using a very unique, highly salient context (Experiment
2), the method produced a qualitative replication, but it was small in magnitude.
A critical assumption of the reconsolidation account, that the target list is
reactivated and destabilized during re-exposure to the study context, was not
supported (Experiment 3). Although troubling for the reconsolidation account, the
findings can be easily accommodated by an alternative account that does not
assume additional neurobiological processes underlying the destabilization of
consolidated memories, instead explaining intrusion rates simply in terms of well
established cognitive effects, such as item-to-context binding and interference
during retrieval.
PMID- 28416634
TI - A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a
Transcription Factor to an E3 Ubiquitin Ligase.
AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
that is known as a mediator of toxic responses. Recently, it was shown that the
AhR has dual functions. Besides being a transcription factor, it also possesses
an intrinsic E3 ubiquitin ligase function that targets, e.g., the steroid
receptors for proteasomal degradation. The aim of this study was to identify the
molecular switch that determines whether the AhR acts as a transcription factor
or an E3 ubiquitin ligase. To do this, we used the breast cancer cell line MCF7,
which expresses a functional estrogen receptor alpha (ERalpha) signaling pathway.
Our data suggest that aryl hydrocarbon receptor nuclear translocator (ARNT) plays
an important role in the modulation of the dual functions of the AhR. ARNT
knockdown dramatically impaired the transcriptional activation properties of the
ligand-activated AhR but did not affect its E3 ubiquitin ligase function. The
availability of ARNT itself is modulated by another basic helix-loop-helix (bHLH)
Per-ARNT-SIM (PAS) protein, the repressor of AhR function (AhRR). MCF7 cells
overexpressing the AhRR showed lower ERalpha protein levels, reduced
responsiveness to estradiol, and reduced growth rates. Importantly, when these
cells were used to produce estrogen-dependent xenograft tumors in SCID mice, we
also observed lower ERalpha protein levels and a reduced tumor mass, implying a
tumor-suppressive-like function of the AhR in MCF7 xenograft tumors.
PMID- 28416635
TI - VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell
Cycle Transcription Factor FoxM1.
AB - The oncogenic transcription factor FoxM1 plays a vital role in cell cycle
progression, is activated in numerous human malignancies, and is linked to
chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase
and its substrate receptor, VprBP/DCAF1 (CRL4VprBP), which we show regulate FoxM1
ubiquitylation and degradation. Paradoxically, we also found that the substrate
receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of
FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression
strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is
reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is
ligase independent. This implies a nonproteolytic activation mechanism that is
reminiscent of, yet distinct from, the ubiquitin-dependent transactivation of the
oncoprotein Myc by other E3s. Significantly, VprBP protein levels were
upregulated in high-grade serous ovarian patient tumors, where the FoxM1
signature is amplified. These data suggest that FoxM1 abundance and activity are
controlled by VprBP and highlight the functional repurposing of E3 ligase
substrate receptors independent of the ubiquitin system.
PMID- 28416636
TI - p53 Dynamically Directs TFIID Assembly on Target Gene Promoters.
AB - p53 is a central regulator that turns on vast gene networks to maintain cellular
integrity in the presence of various stimuli. p53 activates transcription
initiation in part by aiding recruitment of TFIID to the promoter. However, the
precise means by which p53 dynamically interacts with TFIID to facilitate
assembly on target gene promoters remains elusive. To address this key issue, we
have undertaken an integrated approach involving single-molecule fluorescence
microscopy, single-particle cryo-electron microscopy, and biochemistry. Our real
time single-molecule imaging data demonstrate that TFIID alone binds poorly to
native p53 target promoters. p53 unlocks TFIID's ability to bind DNA by
stabilizing TFIID contacts with both the core promoter and a region within p53's
response element. Analysis of single-molecule dissociation kinetics reveals that
TFIID interacts with promoters via transient and prolonged DNA binding modes that
are each regulated by p53. Importantly, our structural work reveals that TFIID's
conversion to a rearranged DNA binding conformation is enhanced in the presence
of DNA and p53. Notably, TFIID's interaction with DNA induces p53 to rapidly
dissociate, which likely leads to additional rounds of p53-mediated recruitment
of other basal factors. Collectively, these findings indicate that p53
dynamically escorts and loads TFIID onto its target promoters.
PMID- 28416638
TI - Eya2, a Target Activated by Plzf, Is Critical for PLZF-RARA-Induced
Leukemogenesis.
AB - PLZF is a transcription factor that confers aberrant self-renewal in
leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia
(APL) through differentiation block. However, the molecular mechanisms of
aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly
understood. To investigate these mechanisms, comprehensive expression profiling
of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed,
which revealed the involvement of a key transcriptional coactivator, Eya2, a
target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal.
Indeed, PLZF-RARA as well as Plzf rendered those cells immortalized through
upregulation of Eya2. Eya2 also led to immortalization without differentiation
block, while depletion of Eya2 suppressed clonogenicity in cells immortalized by
PLZF-RARA without influence on differentiation and apoptosis. Interestingly,
cancer outlier profile analysis of human samples of acute myeloid leukemia (AML)
in The Cancer Genome Atlas (TCGA) revealed a subtype of AML that strongly
expressed EYA2 In addition, gene set enrichment analysis of human AML samples,
including TCGA data, showed that this subtype of AML was more closely associated
with the properties of leukemic stem cells in its gene expression signature than
other AMLs. Therefore, EYA2 may be a target for molecular therapy in this subtype
of AML, including PLZF-RARA APL.
PMID- 28416639
TI - Absent progesterone receptor expression in the lymph node metastases of ER
positive, HER2-negative breast cancer is associated with relapse on tamoxifen.
AB - AIMS: Progesterone receptor (PR) expression is prognostic in early stage breast
cancer. There are several reports of discordant expression between primary tumour
and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER)
and PR. We sought to determine whether expression of these biomarkers in the
synchronous ALN metastases of ER positive (+), HER2 negative (-) breast cancer
could provide more accurate prognostic information. METHODS: The retrospective
cohort included 229 patients from a single institution with ER+, HER2- breast
cancer who had synchronous ALN metastatic disease (2005-2014). PR expression was
correlated with relapse-free survival, and subset analysis was performed for
patients who received adjuvant tamoxifen or an aromatase inhibitor. RESULTS: One
patient had an ER+ primary tumour, which was ER- in the ALN metastasis. 27
(11.3%) were PR- in the primary tumour and 56 (23.6%) in the ALN metastasis. The
predominant change was from PR+ in the primary tumour to PR- in the lymph node.
Absence of PR expression in the ALN was significantly associated with relapse;
however, this was not the case in the primary tumour. In a subset analysis of
patients taking adjuvant endocrine therapy, poorer prognosis was limited to those
with PR- metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No
significant prognostic effect of PR- metastases in patients taking aromatase
inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312). CONCLUSIONS:
Evaluation of PR expression in ALN metastasis may enable prediction of patients
who are less likely to benefit from adjuvant tamoxifen. This study should be
replicated in other cohorts.
PMID- 28416637
TI - A Kinase-Independent Role for Cyclin-Dependent Kinase 19 in p53 Response.
AB - The human Mediator complex regulates RNA polymerase II transcription genome-wide.
A general factor that regulates Mediator function is the four-subunit kinase
module, which contains either cyclin-dependent kinase 8 (CDK8) or CDK19. Whereas
CDK8 is linked to specific signaling cascades and oncogenesis, the cellular roles
of its paralog, CDK19, are poorly studied. We discovered that osteosarcoma cells
(SJSA) are naturally depleted of CDK8 protein. Whereas stable CDK19 knockdown was
tolerated in SJSA cells, proliferation was reduced. Notably, proliferation
defects were rescued upon the reexpression of wild-type or kinase-dead CDK19.
Comparative RNA sequencing analyses showed reduced expression of mitotic genes
and activation of genes associated with cholesterol metabolism and the p53
pathway in CDK19 knockdown cells. SJSA cells treated with 5-fluorouracil, which
induces metabolic and genotoxic stress and activates p53, further implicated
CDK19 in p53 target gene expression. To better probe the p53 response, SJSA cells
(shCDK19 versus shCTRL) were treated with the p53 activator nutlin-3. Remarkably,
CDK19 was required for SJSA cells to return to a proliferative state after nutlin
3 treatment, and this effect was kinase independent. These results implicate
CDK19 as a regulator of p53 stress responses and suggest a role for CDK19 in
cellular resistance to nutlin-3.
PMID- 28416640
TI - Microsatellite analysis of sporadic and hereditary gynaecological cancer in
routine diagnostics.
AB - Microsatellite instability (MSI) testing is tricky in gynaecological cancers
(GC). Thus, we aimed to describe the instability patterns to improve MSI test
interpretation in sporadic and hereditary GCs. Ninety-five cases, including
uterine and ovarian cancers, with known genetic and immunohistochemical (IHC)
features, were analysed for MSI by a mononucleotide repeats pentaplex (MRP). We
identified 13 ambiguous cases that did not fully meet MSI criteria ('borderline'
cases, B-MSI), which were mainly represented by MSH2/MSH6-deficient and Lynch
syndrome cases. Also, we evaluated nine additional loci of candidate MSI markers
that did not improve the detection of MSI cases, but might be useful for
discordant or borderline samples. In conclusion, although MSI and IHC test are
highly concordant, a subset of ambiguous MSI cases deserves a careful
interpretation in particular when MSH2/MSH6 are involved. RPL22 and SRPR testing
may be useful to integrate MRP panel for the analysis of critical cases.
PMID- 28416641
TI - Unusual presentation of a skin rash.
PMID- 28416642
TI - Estimating the burden of occupational cancer: assessing bias and uncertainty.
AB - BACKGROUND AND OBJECTIVES: We aimed to estimate credibility intervals for the
British occupational cancer burden to account for bias uncertainty, using a
method adapted from Greenland's Monte Carlo sensitivity analysis. METHODS: The
attributable fraction (AF) methodology used for our cancer burden estimates
requires risk estimates and population proportions exposed for each agent/cancer
pair. Sources of bias operating on AF estimator components include non
portability of risk estimates, inadequate models, inaccurate data including
unknown cancer latency and employment turnover and compromises in using the
available estimators. Each source of bias operates on a component of the AF
estimator. Independent prior distributions were estimated for each bias, or
graphical sensitivity analysis was used to identify plausible distribution ranges
for the component variables, with AF recalculated following Monte Carlo repeated
sampling from these distributions. The methods are illustrated using the example
of lung cancer due to occupational exposure to respirable crystalline silica in
men. RESULTS: Results are presented graphically for a hierarchy of biases
contributing to an overall credibility interval for lung cancer and respirable
crystalline silica exposure. An overall credibility interval of 2.0% to 16.2% was
estimated for an AF of 3.9% in men. Choice of relative risk and employment
turnover were shown to contribute most to overall estimate uncertainty. Bias from
using an incorrect estimator makes a much lower contribution. CONCLUSIONS: The
method illustrates the use of credibility intervals to indicate relative
contributions of important sources of uncertainty and identifies important data
gaps; results depend greatly on the priors chosen.
PMID- 28416643
TI - Can serum cytokine profile discriminate irritant-induced and allergen-induced
symptoms? A cross-sectional study in workers mostly exposed to laboratory
animals.
AB - BACKGROUND: In workers exposed mostly to laboratory animals (LA), symptoms may be
due to irritants or allergens. Correct aetiological diagnosis is important for
health surveillance. OBJECTIVES: This study aims to test whether work-related
(WR) allergen-induced symptoms are associated with a cytokine profile distinct
from that due to irritants. METHODS: In a cross-sectional study (n=114), WR
respiratory and/or skin symptoms were assessed through a standardised clinical
examination and sensitisation to rat and/or mouse allergen determined by serum
immunoglobulin E. Serum cytokine concentrations were measured by multiplex
assays. The predefined cytokine profiles 'sensitiser' (interleukin (IL)-4, IL-5,
IL-13, eotaxin-1) and 'irritation' (IL-8, IL-17A, IL-17F, IL-22) were considered
positive, when >=3 concentrations exceeded the 95th percentile of the
asymptomatic non-sensitised group. Results were examined by hierarchical
clustering analyses (HCA) and multiple linear regression. Explorative analyses
were carried out for nine additional cytokines. Exposure to allergens and
endotoxin was assessed in a subpopulation. RESULTS: The prevalence of the profile
'irritation' was comparable in 28 symptomatic non-sensitised workers and 71
asymptomatic non-sensitised workers. HCA showed that nearly all symptomatic non
sensitised workers were gathered in two subclusters, characterised by high IL-17A
levels, but different IL-8 levels. Multiple linear regression identified drug
consumption and current complaints as confounders. Sensitised subjects were too
few (n=14) for testing the profile 'sensitiser'. CONCLUSIONS: In this unselected
population of LA workers, the profile 'irritation' did not prove to be a valuable
health surveillance tool. Low power precluded assessment of the profile
'sensitiser'. The increased IL-17A concentration may originate from irritative
constituents of organic dust.
PMID- 28416644
TI - Evaluation of Different Estimation Methods for Accuracy and Precision in
Biological Assay Validation.
AB - Biological assays (bioassays) are procedures to estimate the potency of a
substance by studying its effects on living organisms, tissues, and cells.
Bioassays are essential tools for gaining insight into biologic systems and
processes including, for example, the development of new drugs and monitoring
environmental pollutants. Two of the most important parameters of bioassay
performance are relative accuracy (bias) and precision. Although general
strategies and formulas are provided in USP<1033>, a comprehensive understanding
of the definitions of bias and precision remain elusive. Additionally, whether
there is a beneficial use of data transformation in estimating intermediate
precision remains unclear. Finally, there are various statistical estimation
methods available that often pose a dilemma for the analyst who must choose the
most appropriate method. To address these issues, we provide both a rigorous
definition of bias and precision as well as three alternative methods for
calculating relative standard deviation (RSD). All methods perform similarly when
the RSD <=10%. However, the USP estimates result in larger bias and root-mean
square error (RMSE) compared to the three proposed methods when the actual
variation was large. Therefore, the USP method should not be used for routine
analysis. For data with moderate skewness and deviation from normality, the
estimates based on the original scale perform well. The original scale method is
preferred, and the method based on log-transformation may be used for noticeably
skewed data.LAY ABSTRACT: Biological assays, or bioassays, are essential in the
development and manufacture of biopharmaceutical products for potency testing and
quality monitoring. Two important parameters of assay performance are relative
accuracy (bias) and precision. The definitions of bias and precision in USP
<1033> are elusive and confusing. Another complicating issue is whether log
transformation should be used for calculating the intermediate precision. It is
often challenging for analysts to pick the most appropriate estimation method. To
address these issues, we give a rigorous definition of bias and precision and
provide three alternative methods of calculating RSD. We demonstrate that the RSD
formula in USP <1033> tends to have larger bias and root-mean-square error (RMSE)
than the three proposed methods.
PMID- 28416645
TI - Performance Stability of Silicone Oxide-Coated Plastic Parenteral Vials.
AB - A new packaging system was developed for parenteral pharmaceuticals that combines
the best attributes of plastic and glass without their respective drawbacks. This
technological advancement is based on the synergy between high-precision
injection-molded plastics and plasma coating technology. The result is a shatter
resistant, optically clear, low-particulate, and chemically durable packaging
system. The demand for this product is driven by the expanding market, regulatory
constraints, and product recalls for injectable drugs and biologics packaged in
traditional glass materials. It is shown that this new packaging system meets or
exceeds the important performance characteristics of glass, especially in
eliminating the glass delamination and breakage that has been observed in many
products. The new packaging system is an engineered, multilayer, glass-coated
plastic composite that provides a chemically stable contact surface and oxygen
barrier performance that exceeds a 2 year shelf life requirement. Evaluation of
the coating system characteristics and performance stability to chemical,
temperature, and mechanical extremes are reported herein.LAY ABSTRACT: A new
packaging system for parenteral pharmaceuticals was developed that combines the
best attributes of plastic and glass without their respective drawbacks. This
technological advancement is based on the synergy between high-precision
injection-molded plastics and plasma coating technology. The result is a shatter
resistant, optically clear, low-particulate, and chemically durable packaging
system. It is shown that this new packaging system meets or exceeds the important
performance characteristics of glass, especially in eliminating the glass
delamination and breakage that has been observed in many products. The new
packaging system is an engineered, multilayer, glass-coated plastic composite
that provides a chemically stable contact surface and oxygen barrier performance
that exceeds a 2 year shelf life requirement. Evaluation of the coating system
characteristics and performance stability to chemical, temperature, and
mechanical extremes are reported herein.
PMID- 28416646
TI - Increasing Patient Safety by Closing the Sterile Production Gap-Part 3-Moist Heat
Resistance of Bioburden.
AB - Terminal sterilization is considered the preferred means for the production of
sterile drug products, as it affords enhanced safety for the patient because the
formulation is sterilized in its sealed, final container. Despite the obvious
patient benefits, the use of terminal sterilization is artificially constrained
by unreasonable expectations for the minimum time-temperature process to be used.
The core misunderstanding with terminal sterilization is the notion that
destruction of a high population of a resistant biological indicator
microorganism is required. More contemporary thinking on sterilization
acknowledges that the bioburden is the actual target in sterilization and its
destruction must be assured. In the application of low-temperature moist heat for
terminal sterilization, especially subsequent to aseptic processing, establishing
the pre-sterilization bioburden to consider has proven challenging. Environmental
monitoring survey data has determined the identity of potential microorganisms
but not their resistance to sterilization. This review article provides
information on the moist heat resistance of vegetative and sporeforming
microorganisms that might be present. The first paper in this series provided the
overall background and described the benefits to patient, producer, and regulator
of low-temperature moist heat for terminal sterilization. The second paper
outlined validation and operational advice that can be used in the
implementation. This final effort concludes the series and provides insight into
potential bioburden and its resistance.LAY ABSTRACT: Terminal sterilization is
considered the preferred means for the production of sterile drug products as it
affords enhanced safety for the patient as the formulation is filled into its
final container, sealed and sterilized. Despite the obvious patient benefits, the
use of terminal sterilization is artificially constrained by unreasonable
expectations for the minimum time-temperature process to be used. The primary
consideration in terminal sterilization is the reliable destruction of the
bioburden. The earlier manuscripts in this series described the principles and
implementation of low temperature terminal sterilization processes where the
sterilization conditions would destroy the expected bioburden present. To
accomplish that reliably knowledge of the bioburden expected resistance to moist
heat is necessary. This review article will identify publications where that data
can be found.
PMID- 28416647
TI - Identifiability, reducibility, and adaptability in allosteric macromolecules.
AB - The ability of macromolecules to transduce stimulus information at one site into
conformational changes at a distant site, termed "allostery," is vital for
cellular signaling. Here, we propose a link between the sensitivity of allosteric
macromolecules to their underlying biophysical parameters, the interrelationships
between these parameters, and macromolecular adaptability. We demonstrate that
the parameters of a canonical model of the mSlo large-conductance Ca2+-activated
K+ (BK) ion channel are non-identifiable with respect to the equilibrium open
probability-voltage relationship, a common functional assay. We construct a
reduced model with emergent parameters that are identifiable and expressed as
combinations of the original mechanistic parameters. These emergent parameters
indicate which coordinated changes in mechanistic parameters can leave assay
output unchanged. We predict that these coordinated changes are used by
allosteric macromolecules to adapt, and we demonstrate how this prediction can be
tested experimentally. We show that these predicted parameter compensations are
used in the first reported allosteric phenomena: the Bohr effect, by which
hemoglobin adapts to varying pH.
PMID- 28416648
TI - Isoflurane modulates activation and inactivation gating of the prokaryotic Na+
channel NaChBac.
AB - Voltage-gated Na+ channels (Nav) have emerged as important presynaptic targets
for volatile anesthetic (VA) effects on synaptic transmission. However, the
detailed biophysical mechanisms by which VAs modulate Nav function remain
unclear. VAs alter macroscopic activation and inactivation of the prokaryotic Na+
channel, NaChBac, which provides a useful structural and functional model of
mammalian Nav Here, we study the effects of the common general anesthetic
isoflurane on NaChBac function by analyzing macroscopic Na+ currents (INa) in
wild-type (WT) channels and mutants with impaired (G229A) or enhanced (G219A)
inactivation. We use a previously described six-state Markov model to analyze
empirical WT and mutant NaChBac channel gating data. The model reproduces the
mean empirical gating manifest in INa time courses and optimally estimates
microscopic rate constants, valences (z), and fractional electrical distances (x)
of forward and backward transitions. The model also reproduces gating observed
for all three channels in the absence or presence of isoflurane, providing
further validation. We show using this model that isoflurane increases forward
activation and inactivation rate constants at 0 mV, which are associated with
estimated chemical free energy changes of approximately -0.2 and -0.7 kcal/mol,
respectively. Activation is voltage dependent (z ~ 2e0, x ~ 0.3), inactivation
shows little voltage dependence, and isoflurane has no significant effect on
either. Forward inactivation rate constants are more than 20-fold greater than
backward rate constants in the absence or presence of isoflurane. These results
indicate that isoflurane modulates NaChBac gating primarily by increasing forward
activation and inactivation rate constants. These findings support accumulating
evidence for multiple sites of anesthetic interaction with the channel.
PMID- 28416649
TI - Optic nerve astrocyte reactivity protects function in experimental glaucoma and
other nerve injuries.
AB - Reactive remodeling of optic nerve head astrocytes is consistently observed in
glaucoma and other optic nerve injuries. However, it is unknown whether this
reactivity is beneficial or harmful for visual function. In this study, we used
the Cre recombinase (Cre)-loxP system under regulation of the mouse glial
fibrillary acidic protein promoter to knock out the transcription factor signal
transducer and activator of transcription 3 (STAT3) from astrocytes and test the
effect this has on reactive remodeling, ganglion cell survival, and visual
function after experimental glaucoma and nerve crush. After injury, STAT3
knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling;
astrocytes largely maintained their honeycomb organization and glial tubes. These
changes were associated with increased loss of ganglion cells and visual function
over a 30-day period. Thus, reactive astrocytes play a protective role,
preserving visual function. STAT3 signaling is an important mediator of various
aspects of the reactive phenotype within optic nerve astrocytes.
PMID- 28416651
TI - AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse
model of tauopathy.
AB - Tauopathies are characterized by the progressive accumulation of
hyperphosphorylated, aggregated forms of tau. Our laboratory has previously
demonstrated that passive immunization with an anti-tau antibody, HJ8.5,
decreased accumulation of pathological tau in a human P301S tau-expressing
transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To
investigate whether the Fc domain of HJ8.5 is required for the therapeutic
effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5
with variable linker lengths, all specific to human tau. Based on different
binding properties, we selected two anti-tau scFvs and tested their efficacy in
vivo by adeno-associated virus-mediated gene transfer to the brain of P301S-tg
mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated
tau in brain tissue of P301S-tg mice, associated with a decrease in detergent
soluble tau species. Interestingly, these mice showed substantial levels of scFvs
in the cerebrospinal fluid without significant effects on total extracellular tau
levels. Therefore, our study provides a novel strategy for anti-tau
immunotherapeutics that potentially limits a detrimental proinflammatory
response.
PMID- 28416650
TI - Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9
elicited IFN response in pDCs.
AB - TLR7/9 signals are capable of mounting massive interferon (IFN) response in
plasmacytoid dendritic cells (pDCs) immediately after viral infection, yet the
involvement of epigenetic regulation in this process has not been documented.
Here, we report that zinc finger CXXC family epigenetic regulator CXXC5 is highly
expressed in pDCs, where it plays a crucial role in TLR7/9- and virus-induced IFN
response. Notably, genetic ablation of CXXC5 resulted in aberrant methylation of
the CpG-containing island (CGI) within the Irf7 gene and impaired IRF7 expression
in steady-state pDCs. Mechanistically, CXXC5 is responsible for the recruitment
of DNA demethylase Tet2 to maintain the hypomethylation of a subset of CGIs, a
process coincident with active histone modifications and constitutive
transcription of these CGI-containing genes. Consequently, CXXC5-deficient mice
had compromised early IFN response and became highly vulnerable to infection by
herpes simplex virus and vesicular stomatitis virus. Together, our results
identify CXXC5 as a novel epigenetic regulator for pDC-mediated antiviral
response.
PMID- 28416652
TI - Simplification of the HOSPITAL score for predicting 30-day readmissions.
AB - OBJECTIVE: The HOSPITAL score has been widely validated and accurately identifies
high-risk patients who may mostly benefit from transition care interventions.
Although this score is easy to use, it has the potential to be simplified without
impacting its performance. We aimed to validate a simplified version of the
HOSPITAL score for predicting patients likely to be readmitted. DESIGN AND
SETTING: Retrospective study in 9 large hospitals across 4 countries, from
January through December 2011. PARTICIPANTS: We included all consecutively
discharged medical patients. We excluded patients who died before discharge or
were transferred to another acute care facility. MEASUREMENTS: The primary
outcome was any 30-day potentially avoidable readmission. We simplified the score
as follows: (1) 'discharge from an oncology division' was replaced by 'cancer
diagnosis or discharge from an oncology division'; (2) 'any procedure' was left
out; (3) patients were categorised into two risk groups (unlikely and likely to
be readmitted). The performance of the simplified HOSPITAL score was evaluated
according to its overall accuracy, its discriminatory power and its calibration.
RESULTS: Thirty-day potentially avoidable readmission rate was 9.7% (n=11 307/117
065 patients discharged). Median of the simplified HOSPITAL score was 3 points
(IQR 2-5). Overall accuracy was very good with a Brier score of 0.08 and
discriminatory power remained good with a C-statistic of 0.69 (95% CI 0.68 to
0.69). The calibration was excellent when comparing the expected with the
observed risk in the two risk categories. CONCLUSIONS: The simplified HOSPITAL
score has good performance for predicting 30-day readmission. Prognostic accuracy
was similar to the original version, while its use is even easier. This
simplified score may provide a good alternative to the original score depending
on the setting.
PMID- 28416653
TI - Can processing demands explain toddlers' performance in false-belief tasks?
PMID- 28416654
TI - Reconstructed ancestral enzymes suggest long-term cooling of Earth's photic zone
since the Archean.
AB - Paleotemperatures inferred from the isotopic compositions (delta18O and
delta30Si) of marine cherts suggest that Earth's oceans cooled from 70 +/- 15
degrees C in the Archean to the present ~15 degrees C. This interpretation,
however, has been subject to question due to uncertainties regarding oceanic
isotopic compositions, diagenetic or metamorphic resetting of the isotopic
record, and depositional environments. Analyses of the thermostability of
reconstructed ancestral enzymes provide an independent method by which to assess
the temperature history inferred from the isotopic evidence. Although previous
studies have demonstrated extreme thermostability in reconstructed archaeal and
bacterial proteins compatible with a hot early Earth, taxa investigated may have
inhabited local thermal environments that differed significantly from average
surface conditions. We here present thermostability measurements of reconstructed
ancestral enzymatically active nucleoside diphosphate kinases (NDKs) derived from
light-requiring prokaryotic and eukaryotic phototrophs having widely separated
fossil-based divergence ages. The ancestral environmental temperatures thereby
determined for these photic-zone organisms--shown in modern taxa to correlate
strongly with NDK thermostability--are inferred to reflect ancient surface
environment paleotemperatures. Our results suggest that Earth's surface
temperature decreased over geological time from ~65-80 degrees C in the Archean,
a finding consistent both with previous isotope-based and protein reconstruction
based interpretations. Interdisciplinary studies such as those reported here
integrating genomic, geologic, and paleontologic data hold promise for providing
new insight into the coevolution of life and environment over Earth history.
PMID- 28416655
TI - Economic inequality increases risk taking.
AB - Rising income inequality is a global trend. Increased income inequality has been
associated with higher rates of crime, greater consumer debt, and poorer health
outcomes. The mechanisms linking inequality to poor outcomes among individuals
are poorly understood. This research tested a behavioral account linking
inequality to individual decision making. In three experiments (n = 811), we
found that higher inequality in the outcomes of an economic game led participants
to take greater risks to try to achieve higher outcomes. This effect of unequal
distributions on risk taking was driven by upward social comparisons. Next, we
estimated economic risk taking in daily life using large-scale data from internet
searches. Risk taking was higher in states with greater income inequality, an
effect driven by inequality at the upper end of the income distribution. Results
suggest that inequality may promote poor outcomes, in part, by increasing risky
behavior.
PMID- 28416656
TI - Effect of cholesterol on the molecular structure and transitions in a clinical
grade lung surfactant extract.
AB - The lipid-protein film covering the interface of the lung alveolar in mammals is
vital for proper lung function and its deficiency is related to a range of
diseases. Here we present a molecular-level characterization of a clinical-grade
porcine lung surfactant extract using a multitechnique approach consisting of
[Formula: see text]-[Formula: see text] solid-state nuclear magnetic
spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The
detailed characterization presented for reconstituted membranes of a lung extract
demonstrates that the molecular structure of lung surfactant strongly depends on
the concentration of cholesterol. If cholesterol makes up about 11% of the total
dry weight of lung surfactant, the surfactant extract adopts a single liquid
ordered lamellar phase, [Formula: see text], at physiological temperatures. This
[Formula: see text] phase gradually changes into a liquid-disordered lamellar
phase, [Formula: see text], when the temperature is increased by a few degrees.
In the absence of cholesterol the system segregates into one lamellar gel phase
and one [Formula: see text] phase. Remarkably, it was possible to measure a large
set of order parameter magnitudes [Formula: see text] from the liquid-disordered
and -ordered lamellar phases and assign them to specific C-H bonds of the
phospholipids in the biological extract with no use of isotopic labeling. These
findings with molecular details on lung surfactant mixtures together with the
presented NMR methodology may guide further development of pulmonary surfactant
pharmaceuticals that better mimic the physiological self-assembly compositions
for treatment of pathological states such as respiratory distress syndrome.
PMID- 28416657
TI - Role of atmospheric oxidation in recent methane growth.
AB - The growth in global methane (CH4) concentration, which had been ongoing since
the industrial revolution, stalled around the year 2000 before resuming globally
in 2007. We evaluate the role of the hydroxyl radical (OH), the major CH4 sink,
in the recent CH4 growth. We also examine the influence of systematic
uncertainties in OH concentrations on CH4 emissions inferred from atmospheric
observations. We use observations of 1,1,1-trichloroethane (CH3CCl3), which is
lost primarily through reaction with OH, to estimate OH levels as well as CH3CC3
emissions, which have uncertainty that previously limited the accuracy of OH
estimates. We find a 64-70% probability that a decline in OH has contributed to
the post-2007 methane rise. Our median solution suggests that CH4 emissions
increased relatively steadily during the late 1990s and early 2000s, after which
growth was more modest. This solution obviates the need for a sudden
statistically significant change in total CH4 emissions around the year 2007 to
explain the atmospheric observations and can explain some of the decline in the
atmospheric 13CH4/12CH4 ratio and the recent growth in C2H6 Our approach
indicates that significant OH-related uncertainties in the CH4 budget remain, and
we find that it is not possible to implicate, with a high degree of confidence,
rapid global CH4 emissions changes as the primary driver of recent trends when
our inferred OH trends and these uncertainties are considered.
PMID- 28416658
TI - Correction to Supporting Information for Falahati and Wieschaus, Independent
active and thermodynamic processes govern the nucleolus assembly in vivo.
PMID- 28416659
TI - Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH
stability.
AB - Hippo signaling controls the expression of genes regulating cell proliferation
and survival and organ size. The regulation of core components in the Hippo
pathway by phosphorylation has been extensively investigated, but the roles of
ubiquitination-deubiquitination processes are largely unknown. To identify
deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA
screening and found that YOD1 controls biological responses mediated by YAP/TAZ.
Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances
the stability of ITCH, which leads to reduced levels of LATS and a subsequent
increase in the YAP/TAZ level. Furthermore, we show that the miR-21-mediated
regulation of YOD1 is responsible for the cell-density-dependent changes in
YAP/TAZ levels. Using a transgenic mouse model, we demonstrate that the inducible
expression of YOD1 enhances the proliferation of hepatocytes and leads to
hepatomegaly in a YAP/TAZ-activity-dependent manner. Moreover, we find a strong
correlation between YOD1 and YAP expression in liver cancer patients. Overall,
our data strongly suggest that YOD1 is a regulator of the Hippo pathway and would
be a therapeutic target to treat liver cancer.
PMID- 28416660
TI - Redefining the essential trafficking pathway for outer membrane lipoproteins.
AB - The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and
an intrinsic antibiotic resistance factor. Lipoproteins are OM components that
function in cell wall synthesis, diverse secretion systems, and antibiotic efflux
pumps. Moreover, each of the essential OM machines that assemble the barrier
requires one or more lipoproteins. This dependence is thought to explain the
essentiality of the periplasmic chaperone LolA and its OM receptor LolB that
traffic lipoproteins to the OM. However, we show that in strains lacking
substrates that are toxic when mislocalized, both LolA and LolB can be completely
bypassed by activating an envelope stress response without compromising
trafficking of essential lipoproteins. We identify the Cpx stress response as a
monitor of lipoprotein trafficking tasked with protecting the cell from
mislocalized lipoproteins. Moreover, our findings reveal that an alternate
trafficking pathway exists that can, under certain conditions, bypass the
functions of LolA and LolB, implying that these proteins do not perform any truly
essential mechanistic steps in lipoprotein trafficking. Instead, these proteins'
key function is to prevent lethal accumulation of mislocalized lipoproteins.
PMID- 28416661
TI - Single-cell analysis of HIV-1 transcriptional activity reveals expression of
proviruses in expanded clones during ART.
AB - Little is known about the fraction of human immunodeficiency virus type 1 (HIV-1)
proviruses that express unspliced viral RNA in vivo or about the levels of HIV
RNA expression within single infected cells. We developed a sensitive cell
associated HIV RNA and DNA single-genome sequencing (CARD-SGS) method to
investigate fractional proviral expression of HIV RNA (1.3-kb fragment of p6,
protease, and reverse transcriptase) and the levels of HIV RNA in single HIV
infected cells from blood samples obtained from individuals with viremia or
individuals on long-term suppressive antiretroviral therapy (ART). Spiking
experiments show that the CARD-SGS method can detect a single cell expressing HIV
RNA. Applying CARD-SGS to blood mononuclear cells in six samples from four HIV
infected donors (one with viremia and not on ART and three with viremia
suppressed on ART) revealed that an average of 7% of proviruses (range: 2-18%)
expressed HIV RNA. Levels of expression varied from one to 62 HIV RNA molecules
per cell (median of 1). CARD-SGS also revealed the frequent expression of
identical HIV RNA sequences across multiple single cells and across multiple time
points in donors on suppressive ART consistent with constitutive expression of
HIV RNA in infected cell clones. Defective proviruses were found to express HIV
RNA at levels similar to those proviruses that had no obvious defects. CARD-SGS
is a useful tool to characterize fractional proviral expression in single
infected cells that persist despite ART and to assess the impact of experimental
interventions on proviral populations and their expression.
PMID- 28416662
TI - Adapt to more wildfire in western North American forests as climate changes.
AB - Wildfires across western North America have increased in number and size over the
past three decades, and this trend will continue in response to further warming.
As a consequence, the wildland-urban interface is projected to experience
substantially higher risk of climate-driven fires in the coming decades. Although
many plants, animals, and ecosystem services benefit from fire, it is unknown how
ecosystems will respond to increased burning and warming. Policy and management
have focused primarily on specified resilience approaches aimed at resistance to
wildfire and restoration of areas burned by wildfire through fire suppression and
fuels management. These strategies are inadequate to address a new era of western
wildfires. In contrast, policies that promote adaptive resilience to wildfire, by
which people and ecosystems adjust and reorganize in response to changing fire
regimes to reduce future vulnerability, are needed. Key aspects of an adaptive
resilience approach are (i) recognizing that fuels reduction cannot alter
regional wildfire trends; (ii) targeting fuels reduction to increase adaptation
by some ecosystems and residential communities to more frequent fire; (iii)
actively managing more wild and prescribed fires with a range of severities; and
(iv) incentivizing and planning residential development to withstand inevitable
wildfire. These strategies represent a shift in policy and management from
restoring ecosystems based on historical baselines to adapting to changing fire
regimes and from unsustainable defense of the wildland-urban interface to
developing fire-adapted communities. We propose an approach that accepts wildfire
as an inevitable catalyst of change and that promotes adaptive responses by
ecosystems and residential communities to more warming and wildfire.
PMID- 28416663
TI - Bistable metamaterial for switching and cascading elastic vibrations.
AB - The realization of acoustic devices analogous to electronic systems, like diodes,
transistors, and logic elements, suggests the potential use of elastic vibrations
(i.e., phonons) in information processing, for example, in advanced computational
systems, smart actuators, and programmable materials. Previous experimental
realizations of acoustic diodes and mechanical switches have used nonlinearities
to break transmission symmetry. However, existing solutions require operation at
different frequencies or involve signal conversion in the electronic or optical
domains. Here, we show an experimental realization of a phononic transistor-like
device using geometric nonlinearities to switch and amplify elastic vibrations,
via magnetic coupling, operating at a single frequency. By cascading this device
in a tunable mechanical circuit board, we realize the complete set of mechanical
logic elements and interconnect selected ones to execute simple calculations.
PMID- 28416664
TI - Three-dimensional stable lithium metal anode with nanoscale lithium islands
embedded in ionically conductive solid matrix.
AB - Rechargeable batteries based on lithium (Li) metal chemistry are attractive for
next-generation electrochemical energy storage. Nevertheless, excessive dendrite
growth, infinite relative dimension change, severe side reactions, and limited
power output severely impede their practical applications. Although exciting
progress has been made to solve parts of the above issues, a versatile solution
is still absent. Here, a Li-ion conductive framework was developed as a stable
"host" and efficient surface protection to address the multifaceted problems,
which is a significant step forward compared with previous host concepts. This
was fulfilled by reacting overstoichiometry of Li with SiO. The as-formed LixSi
Li2O matrix would not only enable constant electrode-level volume, but also
protect the embedded Li from direct exposure to electrolyte. Because uniform Li
nucleation and deposition can be fulfilled owing to the high-density active Li
domains, the as-obtained nanocomposite electrode exhibits low polarization,
stable cycling, and high-power output (up to 10 mA/cm2) even in carbonate
electrolytes. The Li-S prototype cells further exhibited highly improved capacity
retention under high-power operation (~600 mAh/g at 6.69 mA/cm2). The all-around
improvement on electrochemical performance sheds light on the effectiveness of
the design principle for developing safe and stable Li metal anodes.
PMID- 28416665
TI - Hippo pathway mediates resistance to cytotoxic drugs.
AB - Chemotherapy is widely used for cancer treatment, but its effectiveness is
limited by drug resistance. Here, we report a mechanism by which cell density
activates the Hippo pathway, which in turn inactivates YAP, leading to changes in
the regulation of genes that control the intracellular concentrations of
gemcitabine and several other US Food and Drug Administration (FDA)-approved
oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and
human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived
xenograft models. Nuclear YAP enhances gemcitabine effectiveness by down
regulating multidrug transporters as well by converting gemcitabine to a less
active form, both leading to its increased intracellular availability. Cancer
cell lines carrying genetic aberrations that impair the Hippo signaling pathway
showed heightened sensitivity to gemcitabine. These findings suggest that
"switching off" of the Hippo-YAP pathway could help to prevent or reverse
resistance to some cancer therapies.
PMID- 28416666
TI - Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis.
AB - Despite the wide administration of several effective vaccines, rotavirus (RV)
remains the single most important etiological agent of severe diarrhea in infants
and young children worldwide, with an annual mortality of over 200,000 people. RV
attachment and internalization into target cells is mediated by its outer capsid
protein VP4. To better understand the molecular details of RV entry, we performed
tandem affinity purification coupled with high-resolution mass spectrometry to
map the host proteins that interact with VP4. We identified an actin-binding
protein, drebrin (DBN1), that coprecipitates and colocalizes with VP4 during RV
infection. Importantly, blocking DBN1 function by siRNA silencing, CRISPR
knockout (KO), or chemical inhibition significantly increased host cell
susceptibility to RV infection. Dbn1 KO mice exhibited higher incidence of
diarrhea and more viral antigen shedding in their stool samples compared with the
wild-type littermates. In addition, we found that uptake of other dynamin
dependent cargos, including transferrin, cholera toxin, and multiple viruses, was
also enhanced in DBN1-deficient cells. Inhibition of cortactin or dynamin-2
abrogated the increased virus entry observed in DBN1-deficient cells, suggesting
that DBN1 suppresses dynamin-mediated endocytosis via interaction with cortactin.
Our study unveiled an unexpected role of DBN1 in restricting the entry of RV and
other viruses into host cells and more broadly to function as a crucial negative
regulator of diverse dynamin-dependent endocytic pathways.
PMID- 28416667
TI - Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose
monitoring using a fully integrated wearable platform.
AB - Perspiration-based wearable biosensors facilitate continuous monitoring of
individuals' health states with real-time and molecular-level insight. The
inherent inaccessibility of sweat in sedentary individuals in large volume (>=10
uL) for on-demand and in situ analysis has limited our ability to capitalize on
this noninvasive and rich source of information. A wearable and miniaturized
iontophoresis interface is an excellent solution to overcome this barrier. The
iontophoresis process involves delivery of stimulating agonists to the sweat
glands with the aid of an electrical current. The challenge remains in devising
an iontophoresis interface that can extract sufficient amount of sweat for robust
sensing, without electrode corrosion and burning/causing discomfort in subjects.
Here, we overcame this challenge through realizing an electrochemically enhanced
iontophoresis interface, integrated in a wearable sweat analysis platform. This
interface can be programmed to induce sweat with various secretion profiles for
real-time analysis, a capability which can be exploited to advance our knowledge
of the sweat gland physiology and the secretion process. To demonstrate the
clinical value of our platform, human subject studies were performed in the
context of the cystic fibrosis diagnosis and preliminary investigation of the
blood/sweat glucose correlation. With our platform, we detected the elevated
sweat electrolyte content of cystic fibrosis patients compared with that of
healthy control subjects. Furthermore, our results indicate that oral glucose
consumption in the fasting state is followed by increased glucose levels in both
sweat and blood. Our solution opens the possibility for a broad range of
noninvasive diagnostic and general population health monitoring applications.
PMID- 28416668
TI - Ambiguity in the causes for decadal trends in atmospheric methane and hydroxyl.
AB - Methane is the second strongest anthropogenic greenhouse gas and its atmospheric
burden has more than doubled since 1850. Methane concentrations stabilized in the
early 2000s and began increasing again in 2007. Neither the stabilization nor the
recent growth are well understood, as evidenced by multiple competing hypotheses
in recent literature. Here we use a multispecies two-box model inversion to
jointly constrain 36 y of methane sources and sinks, using ground-based
measurements of methane, methyl chloroform, and the C13/C12 ratio in atmospheric
methane (delta13CH4) from 1983 through 2015. We find that the problem, as
currently formulated, is underdetermined and solutions obtained in previous work
are strongly dependent on prior assumptions. Based on our analysis, the
mathematically most likely explanation for the renewed growth in atmospheric
methane, counterintuitively, involves a 25-Tg/y decrease in methane emissions
from 2003 to 2016 that is offset by a 7% decrease in global mean hydroxyl (OH)
concentrations, the primary sink for atmospheric methane, over the same period.
However, we are still able to fit the observations if we assume that OH
concentrations are time invariant (as much of the previous work has assumed) and
we then find solutions that are largely consistent with other proposed hypotheses
for the renewed growth of atmospheric methane since 2007. We conclude that the
current surface observing system does not allow unambiguous attribution of the
decadal trends in methane without robust constraints on OH variability, which
currently rely purely on methyl chloroform data and its uncertain emissions
estimates.
PMID- 28416669
TI - Coding of navigational affordances in the human visual system.
AB - A central component of spatial navigation is determining where one can and cannot
go in the immediate environment. We used fMRI to test the hypothesis that the
human visual system solves this problem by automatically identifying the
navigational affordances of the local scene. Multivoxel pattern analyses showed
that a scene-selective region of dorsal occipitoparietal cortex, known as the
occipital place area, represents pathways for movement in scenes in a manner that
is tolerant to variability in other visual features. These effects were found in
two experiments: One using tightly controlled artificial environments as stimuli,
the other using a diverse set of complex, natural scenes. A reconstruction
analysis demonstrated that the population codes of the occipital place area could
be used to predict the affordances of novel scenes. Taken together, these results
reveal a previously unknown mechanism for perceiving the affordance structure of
navigable space.
PMID- 28416670
TI - Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause
imbalanced dNTP pools and increased mutagenesis.
AB - Eukaryotic DNA replication fidelity relies on the concerted action of DNA
polymerase nucleotide selectivity, proofreading activity, and DNA mismatch repair
(MMR). Nucleotide selectivity and proofreading are affected by the balance and
concentration of deoxyribonucleotide (dNTP) pools, which are strictly regulated
by ribonucleotide reductase (RNR). Mutations preventing DNA polymerase
proofreading activity or MMR function cause mutator phenotypes and consequently
increased cancer susceptibility. To identify genes not previously linked to high
fidelity DNA replication, we conducted a genome-wide screen in Saccharomyces
cerevisiae using DNA polymerase active-site mutants as a "sensitized mutator
background." Among the genes identified in our screen, three metabolism-related
genes (GLN3, URA7, and SHM2) have not been previously associated to the
suppression of mutations. Loss of either the transcription factor Gln3 or
inactivation of the CTP synthetase Ura7 both resulted in the activation of the
DNA damage response and imbalanced dNTP pools. Importantly, these dNTP imbalances
are strongly mutagenic in genetic backgrounds where DNA polymerase function or
MMR activity is partially compromised. Previous reports have shown that dNTP pool
imbalances can be caused by mutations altering the allosteric regulation of
enzymes involved in dNTP biosynthesis (e.g., RNR or dCMP deaminase). Here, we
provide evidence that mutations affecting genes involved in RNR substrate
production can cause dNTP imbalances, which cannot be compensated by RNR or other
enzymatic activities. Moreover, Gln3 inactivation links nutrient deprivation to
increased mutagenesis. Our results suggest that similar genetic interactions
could drive mutator phenotypes in cancer cells.
PMID- 28416671
TI - Case for the genetic code as a triplet of triplets.
AB - The efficiency of codon translation in vivo is controlled by many factors,
including codon context. At a site early in the Salmonella flgM gene, the effects
on translation of replacing codons Thr6 and Pro8 of flgM with synonymous
alternates produced a 600-fold range in FlgM activity. Synonymous changes at Thr6
and Leu9 resulted in a twofold range in FlgM activity. The level of FlgM activity
produced by any codon arrangement was directly proportional to the degree of in
vivo ribosome stalling at synonymous codons. Synonymous codon suppressors that
corrected the effect of a translation-defective synonymous flgM allele were
restricted to two codons flanking the translation-defective codon. The various
codon arrangements had no apparent effects on flgM mRNA stability or predicted
mRNA secondary structures. Our data suggest that efficient mRNA translation is
determined by a triplet-of-triplet genetic code. That is, the efficiency of
translating a particular codon is influenced by the nature of the immediately
adjacent flanking codons. A model explains these codon-context effects by
suggesting that codon recognition by elongation factor-bound aminoacyl-tRNA is
initiated by hydrogen bond interactions between the first two nucleotides of the
codon and anticodon and then is stabilized by base-stacking energy over three
successive codons.
PMID- 28416672
TI - Bisulfite-converted duplexes for the strand-specific detection and quantification
of rare mutations.
AB - The identification of mutations that are present at low frequencies in clinical
samples is an essential component of precision medicine. The development of
molecular barcoding for next-generation sequencing has greatly enhanced the
sensitivity of detecting such mutations by massively parallel sequencing.
However, further improvements in specificity would be useful for a variety of
applications. We herein describe a technology (BiSeqS) that can increase the
specificity of sequencing by at least two orders of magnitude over and above that
achieved with molecular barcoding and can be applied to any massively parallel
sequencing instrument. BiSeqS employs bisulfite treatment to distinguish the two
strands of molecularly barcoded DNA; its specificity arises from the requirement
for the same mutation to be identified in both strands. Because no library
preparation is required, the technology permits very efficient use of the
template DNA as well as sequence reads, which are nearly all confined to the
amplicons of interest. Such efficiency is critical for clinical samples, such as
plasma, in which only tiny amounts of DNA are often available. We show here that
BiSeqS can be applied to evaluate transversions, as well as small insertions or
deletions, and can reliably detect one mutation among >10,000 wild-type
molecules.
PMID- 28416673
TI - Are there many different routes to becoming a global biodiversity hotspot?
PMID- 28416674
TI - Inducing protein aggregation by extensional flow.
AB - Relative to other extrinsic factors, the effects of hydrodynamic flow fields on
protein stability and conformation remain poorly understood. Flow-induced protein
remodeling and/or aggregation is observed both in Nature and during the large
scale industrial manufacture of proteins. Despite its ubiquity, the relationships
between the type and magnitude of hydrodynamic flow, a protein's structure and
stability, and the resultant aggregation propensity are unclear. Here, we assess
the effects of a defined and quantified flow field dominated by extensional flow
on the aggregation of BSA, beta2-microglobulin (beta2m), granulocyte colony
stimulating factor (G-CSF), and three monoclonal antibodies (mAbs). We show that
the device induces protein aggregation after exposure to an extensional flow
field for 0.36-1.8 ms, at concentrations as low as 0.5 mg mL-1 In addition, we
reveal that the extent of aggregation depends on the applied strain rate and the
concentration, structural scaffold, and sequence of the protein. Finally we
demonstrate the in situ labeling of a buried cysteine residue in BSA during
extensional stress. Together, these data indicate that an extensional flow
readily unfolds thermodynamically and kinetically stable proteins, exposing
previously sequestered sequences whose aggregation propensity determines the
probability and extent of aggregation.
PMID- 28416675
TI - Integrin extension enables ultrasensitive regulation by cytoskeletal force.
AB - Integrins undergo large-scale conformational changes upon activation. Signaling
events driving integrin activation have previously been discussed conceptually,
but not quantitatively. Here, recent measurements of the intrinsic ligand-binding
affinity and free energy of each integrin conformational state on the cell
surface, together with the length scales of conformational change, are used to
quantitatively compare models of activation. We examine whether binding of
cytoskeletal adaptors to integrin cytoplasmic domains is sufficient for
activation or whether exertion of tensile force by the actin cytoskeleton across
the integrin-ligand complex is also required. We find that only the combination
of adaptor binding and cytoskeletal force provides ultrasensitive regulation.
Moreover, switch-like activation by force depends on the large, >130 A length
scale change in integrin extension, which is well tailored to match the free
energy difference between the inactive (bent-closed) and active (extended-open)
conformations. The length scale and energy cost in integrin extension enable
activation by force in the low pN range and appear to be the key specializations
that enable cell adhesion through integrins to be coordinated with cytoskeletal
dynamics.
PMID- 28416676
TI - Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus
in parallel with behavioral outputs.
AB - The temporal order of physiology and behavior in mammals is primarily regulated
by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus
(SCN). Taking advantage of bioluminescence reporters, we monitored the circadian
rhythms of the expression of clock genes Per1 and Bmal1 in the SCN of freely
moving mice and found that the rate of phase shifts induced by a single light
pulse was different in the two rhythms. The Per1-luc rhythm was phase-delayed
instantaneously by the light presented at the subjective evening in parallel with
the activity onset of behavioral rhythm, whereas the Bmal1-ELuc rhythm was phase
delayed gradually, similar to the activity offset. The dissociation was confirmed
in cultured SCN slices of mice carrying both Per1-luc and Bmal1-ELuc reporters.
The two rhythms in a single SCN slice showed significantly different periods in a
long-term (3 wk) culture and were internally desynchronized. Regional specificity
in the SCN was not detected for the period of Per1-luc and Bmal1-ELuc rhythms.
Furthermore, neither is synchronized with circadian intracellular Ca2+ rhythms
monitored by a calcium indicator, GCaMP6s, or with firing rhythms monitored on a
multielectrode array dish, although the coupling between the circadian firing and
Ca2+ rhythms persisted during culture. These findings indicate that the
expressions of two key clock genes, Per1 and Bmal1, in the SCN are regulated in
such a way that they may adopt different phases and free-running periods relative
to each other and are respectively associated with the expression of activity
onset and offset.
PMID- 28416677
TI - Structural toggle in the RNaseH domain of Prp8 helps balance splicing fidelity
and catalytic efficiency.
AB - Pre-mRNA splicing is an essential step of eukaryotic gene expression that
requires both high efficiency and high fidelity. Prp8 has long been considered
the "master regulator" of the spliceosome, the molecular machine that executes
pre-mRNA splicing. Cross-linking and structural studies place the RNaseH domain
(RH) of Prp8 near the spliceosome's catalytic core and demonstrate that prp8
alleles that map to a 17-aa extension in RH stabilize it in one of two mutually
exclusive structures, the biological relevance of which are unknown. We performed
an extensive characterization of prp8 alleles that map to this extension and,
using in vitro and in vivo reporter assays, show they fall into two functional
classes associated with the two structures: those that promote error
prone/efficient splicing and those that promote hyperaccurate/inefficient
splicing. Identification of global locations of endogenous splice-site activation
by lariat sequencing confirms the fidelity effects seen in our reporter assays.
Furthermore, we show that error-prone/efficient RH alleles suppress a prp2 mutant
deficient at promoting the first catalytic step of splicing, whereas
hyperaccurate/inefficient RH alleles exhibit synthetic sickness. Together our
data indicate that prp8 RH alleles link splicing fidelity with catalytic
efficiency by biasing the relative stabilities of distinct spliceosome
conformations. We hypothesize that the spliceosome "toggles" between such error
prone/efficient and hyperaccurate/inefficient conformations during the splicing
cycle to regulate splicing fidelity.
PMID- 28416678
TI - Reply to Rubio-Fernandez et al.: Different traditional false-belief tasks impose
different processing demands for toddlers.
PMID- 28416679
TI - Sensorimotor-independent development of hands and tools selectivity in the visual
cortex.
AB - The visual occipito-temporal cortex is composed of several distinct regions
specialized in the identification of different object kinds such as tools and
bodies. Its organization appears to reflect not only the visual characteristics
of the inputs but also the behavior that can be achieved with them. For example,
there are spatially overlapping responses for viewing hands and tools, which is
likely due to their common role in object-directed actions. How dependent is
occipito-temporal cortex organization on object manipulation and motor
experience? To investigate this question, we studied five individuals born
without hands (individuals with upper limb dysplasia), who use tools with their
feet. Using fMRI, we found the typical selective hand-tool overlap (HTO) not only
in typically developed control participants but also in four of the five
dysplasics. Functional connectivity of the HTO in the dysplasics also showed a
largely similar pattern as in the controls. The preservation of functional
organization in the dysplasics suggests that occipito-temporal cortex
specialization is driven largely by inherited connectivity constraints that do
not require sensorimotor experience. These findings complement discoveries of
intact functional organization of the occipito-temporal cortex in people born
blind, supporting an organization largely independent of any one specific sensory
or motor experience.
PMID- 28416681
TI - Correction for Mann, Core Concept: Unraveling the enigma of fast radio bursts.
PMID- 28416680
TI - Using microsecond single-molecule FRET to determine the assembly pathways of T4
ssDNA binding protein onto model DNA replication forks.
AB - DNA replication is a core biological process that occurs in prokaryotic cells at
high speeds (~1 nucleotide residue added per millisecond) and with high fidelity
(fewer than one misincorporation event per 107 nucleotide additions). The ssDNA
binding protein [gene product 32 (gp32)] of the T4 bacteriophage is a central
integrating component of the replication complex that must continuously bind to
and unbind from transiently exposed template strands during DNA synthesis. We
here report microsecond single-molecule FRET (smFRET) measurements on Cy3/Cy5
labeled primer-template (p/t) DNA constructs in the presence of gp32. These
measurements probe the distance between Cy3/Cy5 fluorophores that label the ends
of a short (15-nt) segment of ssDNA attached to a model p/t DNA construct and
permit us to track the stochastic interconversion between various protein bound
and unbound states. The length of the 15-nt ssDNA lattice is sufficient to
accommodate up to two cooperatively bound gp32 proteins in either of two
positions. We apply a unique multipoint time correlation function analysis to the
microsecond-resolved smFRET data obtained to determine and compare the kinetics
of various possible reaction pathways for the assembly of cooperatively bound
gp32 protein onto ssDNA sequences located at the replication fork. The results of
our analysis reveal the presence and translocation mechanisms of short-lived
intermediate bound states that are likely to play a critical role in the assembly
mechanisms of ssDNA binding proteins at replication forks and other ss duplex
junctions.
PMID- 28416682
TI - Computational modeling of epiphany learning.
AB - Models of reinforcement learning (RL) are prevalent in the decision-making
literature, but not all behavior seems to conform to the gradual convergence that
is a central feature of RL. In some cases learning seems to happen all at once.
Limited prior research on these "epiphanies" has shown evidence of sudden changes
in behavior, but it remains unclear how such epiphanies occur. We propose a
sequential-sampling model of epiphany learning (EL) and test it using an eye
tracking experiment. In the experiment, subjects repeatedly play a strategic game
that has an optimal strategy. Subjects can learn over time from feedback but are
also allowed to commit to a strategy at any time, eliminating all other options
and opportunities to learn. We find that the EL model is consistent with the
choices, eye movements, and pupillary responses of subjects who commit to the
optimal strategy (correct epiphany) but not always of those who commit to a
suboptimal strategy or who do not commit at all. Our findings suggest that EL is
driven by a latent evidence accumulation process that can be revealed with eye
tracking data.
PMID- 28416683
TI - Structure and mechanics of aegagropilae fiber network.
AB - Fiber networks encompass a wide range of natural and manmade materials. The
threads or filaments from which they are formed span a wide range of length
scales: from nanometers, as in biological tissues and bundles of carbon
nanotubes, to millimeters, as in paper and insulation materials. The mechanical
and thermal behavior of these complex structures depends on both the individual
response of the constituent fibers and the density and degree of entanglement of
the network. A question of paramount importance is how to control the formation
of a given fiber network to optimize a desired function. The study of fiber
clustering of natural flocs could be useful for improving fabrication processes,
such as in the paper and textile industries. Here, we use the example of
aegagropilae that are the remains of a seagrass (Posidonia oceanica) found on
Mediterranean beaches. First, we characterize different aspects of their
structure and mechanical response, and second, we draw conclusions on their
formation process. We show that these natural aggregates are formed in open sea
by random aggregation and compaction of fibers held together by friction forces.
Although formed in a natural environment, thus under relatively unconstrained
conditions, the geometrical and mechanical properties of the resulting fiber
aggregates are quite robust. This study opens perspectives for manufacturing
complex fiber network materials.
PMID- 28416684
TI - Discovery of chemoautotrophic symbiosis in the giant shipworm Kuphus polythalamia
(Bivalvia: Teredinidae) extends wooden-steps theory.
AB - The "wooden-steps" hypothesis [Distel DL, et al. (2000) Nature 403:725-726]
proposed that large chemosynthetic mussels found at deep-sea hydrothermal vents
descend from much smaller species associated with sunken wood and other organic
deposits, and that the endosymbionts of these progenitors made use of hydrogen
sulfide from biogenic sources (e.g., decaying wood) rather than from vent fluids.
Here, we show that wood has served not only as a stepping stone between habitats
but also as a bridge between heterotrophic and chemoautotrophic symbiosis for the
giant mud-boring bivalve Kuphus polythalamia This rare and enigmatic species,
which achieves the greatest length of any extant bivalve, is the only described
member of the wood-boring bivalve family Teredinidae (shipworms) that burrows in
marine sediments rather than wood. We show that K. polythalamia harbors sulfur
oxidizing chemoautotrophic (thioautotrophic) bacteria instead of the cellulolytic
symbionts that allow other shipworm species to consume wood as food. The
characteristics of its symbionts, its phylogenetic position within Teredinidae,
the reduction of its digestive system by comparison with other family members,
and the loss of morphological features associated with wood digestion indicate
that K. polythalamia is a chemoautotrophic bivalve descended from wood-feeding
(xylotrophic) ancestors. This is an example in which a chemoautotrophic
endosymbiosis arose by displacement of an ancestral heterotrophic symbiosis and a
report of pure culture of a thioautotrophic endosymbiont.
PMID- 28416685
TI - SNAT7 is the primary lysosomal glutamine exporter required for extracellular
protein-dependent growth of cancer cells.
AB - Lysosomes degrade cellular components sequestered by autophagy or extracellular
material internalized by endocytosis and phagocytosis. The macromolecule building
blocks released by lysosomal hydrolysis are then exported to the cytosol by
lysosomal transporters, which remain undercharacterized. In this study, we
designed an in situ assay of lysosomal amino acid export based on the
transcription factor EB (TFEB), a master regulator of lysosomal biogenesis that
detects lysosomal storage. This assay was used to screen candidate lysosomal
transporters, leading to the identification of sodium-coupled neutral amino acid
transporter 7 (SNAT7), encoded by the SLC38A7 gene, as a lysosomal transporter
highly selective for glutamine and asparagine. Cell fractionation confirmed the
lysosomal localization of SNAT7, and flux measurements confirmed its substrate
selectivity and showed a strong activation by the lysosomal pH gradient.
Interestingly, gene silencing or editing experiments revealed that SNAT7 is the
primary permeation pathway for glutamine across the lysosomal membrane and it is
required for growth of cancer cells in a low free-glutamine environment, when
macropinocytosis and lysosomal degradation of extracellular proteins are used as
an alternative source of amino acids. SNAT7 may, thus, represent a novel target
for glutamine-related anticancer therapies.
PMID- 28416686
TI - NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to
mechanical loads in mice.
AB - Sensory nerves emanating from the dorsal root extensively innervate the surfaces
of mammalian bone, a privileged location for the regulation of biomechanical
signaling. Here, we show that NGF-TrkA signaling in skeletal sensory nerves is an
early response to mechanical loading of bone and is required to achieve maximal
load-induced bone formation. First, the elimination of TrkA signaling in mice
harboring mutant TrkAF592A alleles was found to greatly attenuate load-induced
bone formation induced by axial forelimb compression. Next, both in vivo
mechanical loading and in vitro mechanical stretch were shown to induce the
profound up-regulation of NGF in osteoblasts within 1 h of loading. Furthermore,
inhibition of TrkA signaling following axial forelimb compression was observed to
reduce measures of Wnt/beta-catenin activity in osteocytes in the loaded bone.
Finally, the administration of exogenous NGF to wild-type mice was found to
significantly increase load-induced bone formation and Wnt/beta-catenin activity
in osteocytes. In summary, these findings demonstrate that communication between
osteoblasts and sensory nerves through NGF-TrkA signaling is essential for load
induced bone formation in mice.
PMID- 28416687
TI - Structural and functional innovations in the real-time evolution of new
(betaalpha)8 barrel enzymes.
AB - New genes can arise by duplication and divergence, but there is a fundamental gap
in our understanding of the relationship between these genes, the evolving
proteins they encode, and the fitness of the organism. Here we used
crystallography, NMR dynamics, kinetics, and mass spectrometry to explain the
molecular innovations that arose during a previous real-time evolution
experiment. In that experiment, the (betaalpha)8 barrel enzyme HisA was under
selection for two functions (HisA and TrpF), resulting in duplication and
divergence of the hisA gene to encode TrpF specialists, HisA specialists, and
bifunctional generalists. We found that selection affects enzyme structure and
dynamics, and thus substrate preference, simultaneously and sequentially.
Bifunctionality is associated with two distinct sets of loop conformations, each
essential for one function. We observed two mechanisms for functional
specialization: structural stabilization of each loop conformation and substrate
specific adaptation of the active site. Intracellular enzyme performance,
calculated as the product of catalytic efficiency and relative expression level,
was not linearly related to fitness. Instead, we observed thresholds for each
activity above which further improvements in catalytic efficiency had little if
any effect on growth rate. Overall, we have shown how beneficial substitutions
selected during real-time evolution can lead to manifold changes in enzyme
function and bacterial fitness. This work emphasizes the speed at which adaptive
evolution can yield enzymes with sufficiently high activities such that they no
longer limit the growth of their host organism, and confirms the (betaalpha)8
barrel as an inherently evolvable protein scaffold.
PMID- 28416688
TI - Knockout of the LRRC26 subunit reveals a primary role of LRRC26-containing BK
channels in secretory epithelial cells.
AB - Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory gamma1
subunit of Ca2+- and voltage-dependent BK-type K+ channels. BK channels that
contain LRRC26 subunits are active near normal resting potentials even without
Ca2+, suggesting they play unique physiological roles, likely limited to very
specific cell types and cellular functions. By using Lrrc26 KO mice with a beta
gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells,
especially acinar epithelial cells in lacrimal and salivary glands, and also
goblet and Paneth cells in intestine and colon, although absent from neurons. We
establish the presence of LRRC26 protein in eight secretory tissues or tissues
with significant secretory epithelium and show that LRRC26 protein coassembles
with the pore-forming BK alpha-subunit in at least three tissues: lacrimal gland,
parotid gland, and colon. In lacrimal, parotid, and submandibular gland acinar
cells, LRRC26 KO shifts BK gating to be like alpha-subunit-only BK channels.
Finally, LRRC26 KO mimics the effect of SLO1/BK KO in reducing [K+] in saliva.
LRRC26-containing BK channels are competent to contribute to resting K+ efflux at
normal cell membrane potentials with resting cytosolic Ca2+ concentrations and
likely play a critical physiological role in supporting normal secretory function
in all secretory epithelial cells.
PMID- 28416689
TI - Contractile and chiral activities codetermine the helicity of swimming droplet
trajectories.
AB - Active fluids are a class of nonequilibrium systems where energy is injected into
the system continuously by the constituent particles themselves. Many examples,
such as bacterial suspensions and actomyosin networks, are intrinsically chiral
at a local scale, so that their activity involves torque dipoles alongside the
force dipoles usually considered. Although many aspects of active fluids have
been studied, the effects of chirality on them are much less known. Here, we
study by computer simulation the dynamics of an unstructured droplet of chiral
active fluid in three dimensions. Our model considers only the simplest possible
combination of chiral and achiral active stresses, yet this leads to an
unprecedented range of complex motilities, including oscillatory swimming,
helical swimming, and run-and-tumble motion. Strikingly, whereas the chirality of
helical swimming is the same as the microscopic chirality of torque dipoles in
one regime, the two are opposite in another. Some of the features of these
motility modes resemble those of some single-celled protozoa, suggesting that
underlying mechanisms may be shared by some biological systems and synthetic
active droplets.
PMID- 28416690
TI - Correction for Padilla et al., AgRP to Kiss1 neuron signaling links nutritional
state and fertility.
PMID- 28416691
TI - Neurophysiological dynamics of phrase-structure building during sentence
processing.
AB - Although sentences unfold sequentially, one word at a time, most linguistic
theories propose that their underlying syntactic structure involves a tree of
nested phrases rather than a linear sequence of words. Whether and how the brain
builds such structures, however, remains largely unknown. Here, we used human
intracranial recordings and visual word-by-word presentation of sentences and
word lists to investigate how left-hemispheric brain activity varies during the
formation of phrase structures. In a broad set of language-related areas,
comprising multiple superior temporal and inferior frontal sites, high-gamma
power increased with each successive word in a sentence but decreased suddenly
whenever words could be merged into a phrase. Regression analyses showed that
each additional word or multiword phrase contributed a similar amount of
additional brain activity, providing evidence for a merge operation that applies
equally to linguistic objects of arbitrary complexity. More superficial models of
language, based solely on sequential transition probability over lexical and
syntactic categories, only captured activity in the posterior middle temporal
gyrus. Formal model comparison indicated that the model of multiword phrase
construction provided a better fit than probability-based models at most sites in
superior temporal and inferior frontal cortices. Activity in those regions was
consistent with a neural implementation of a bottom-up or left-corner parser of
the incoming language stream. Our results provide initial intracranial evidence
for the neurophysiological reality of the merge operation postulated by linguists
and suggest that the brain compresses syntactically well-formed sequences of
words into a hierarchy of nested phrases.
PMID- 28416693
TI - Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland
cells.
AB - The Venus flytrap Dionaea muscipula captures insects and consumes their flesh.
Prey contacting touch-sensitive hairs trigger traveling electrical waves. These
action potentials (APs) cause rapid closure of the trap and activate secretory
functions of glands, which cover its inner surface. Such prey-induced
haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling
pathway, which initiates secretion of an acidic hydrolase mixture to decompose
the victim and acquire the animal nutrients. Although postulated since Darwin's
pioneering studies, these secretory events have not been recorded so far. Using
advanced analytical and imaging techniques, such as vibrating ion-selective
electrodes, carbon fiber amperometry, and magnetic resonance imaging, we
monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair
bending or direct application of JA caused a quantal release of oxidizable
material from gland cells monitored as distinct amperometric spikes. Spikes
reminiscent of exocytotic events in secretory animal cells progressively
increased in frequency, reaching steady state 1 d after stimulation. Our data
indicate that trigger-hair mechanical stimulation evokes APs. Gland cells
translate APs into touch-inducible JA signaling that promotes the formation of
secretory vesicles. Early vesicles loaded with H+ and Cl- fuse with the plasma
membrane, hyperacidifying the "green stomach"-like digestive organ, whereas
subsequent ones carry hydrolases and nutrient transporters, together with a
glutathione redox moiety, which is likely to act as the major detected compound
in amperometry. Hence, when glands perceive the haptoelectrical stimulation,
secretory vesicles are tailored to be released in a sequence that optimizes
digestion of the captured animal.
PMID- 28416692
TI - Immunomodulation-accelerated neuronal regeneration following selective rod
photoreceptor cell ablation in the zebrafish retina.
AB - Muller glia (MG) function as inducible retinal stem cells in zebrafish,
completely repairing the eye after damage. The innate immune system has recently
been shown to promote tissue regeneration in which classic wound-healing
responses predominate. However, regulatory roles for leukocytes during cellular
regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are
less well defined. To investigate possible roles innate immune cells play during
retinal cell regeneration, we used intravital microscopy to visualize neutrophil,
macrophage, and retinal microglia responses to induced rod photoreceptor
apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral
macrophage cells responded to rod cell loss, as evidenced by morphological
transitions and increased migration, but did not enter the retina. Retinal
microglia displayed multiple hallmarks of immune cell activation: increased
migration, translocation to the photoreceptor cell layer, proliferation, and
phagocytosis of dying cells. To test function during rod cell regeneration, we
coablated microglia and rod cells or applied immune suppression and quantified
the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation,
and (iii) rod cell replacement. Coablation and immune suppressants applied before
cell loss caused delays in MG/progenitor proliferation rates and slowed the rate
of rod cell replacement. Conversely, immune suppressants applied after cell loss
had been initiated led to accelerated photoreceptor regeneration kinetics,
possibly by promoting rapid resolution of an acute immune response. Our findings
suggest that microglia control MG responsiveness to photoreceptor loss and
support the development of immune-targeted therapeutic strategies for reversing
cell loss associated with degenerative retinal conditions.
PMID- 28416694
TI - Experimental dispersal reveals characteristic scales of biodiversity in a natural
landscape.
AB - Ecological theory posits that dispersal among habitat patches links local
communities and is a key "regional" process that maintains biological diversity.
However, manipulations required to experimentally test regional processes are
infeasible for most systems, and thus more work is needed to detect the scales at
which regional processes manifest and their overall effect on diversity. In a
Californian grassland, a hotspot for global biodiversity, we used a seed vacuum
to increase dispersal at spatial scales varying from 1 m to 10 km while
maintaining a realistic spatial structure of species pools and environmental
conditions. We found that dispersal limitation has a profound influence on
diversity; species richness increased with the spatial scale of seed mixing,
doubling in plots that received seed from large (>=5 km) compared with small (<=5
m) scales. This increase in diversity corresponded to an increase in how well
species distributions were explained by environmental conditions, from modest at
small scales (R2 = 0.34) to strong at large scales (R2 = 0.52). Responses to the
spatial scale of seed mixing were nonlinear, with no differences below 5 m or
above 5 km. Nonlinearities were explained by homogeneity of environmental
conditions below 5 m and by a lack of additional variation in the species pool
above 5 km. Our approach of manipulating natural communities at different spatial
scales reveals (i) nonlinear transitions in the importance of environmental
sorting and dispersal, and (ii) the negative effects of dispersal limitation on
local diversity, consistent with previous research suggesting that large numbers
of species are headed toward regional extinction.
PMID- 28416695
TI - Peter C. Nowell (1928-2016).
PMID- 28416696
TI - Zeaxanthin-dependent nonphotochemical quenching does not occur in photosystem I
in the higher plant Arabidopsis thaliana.
AB - Nonphotochemical quenching (NPQ) is the process that protects the photosynthetic
apparatus of plants and algae from photodamage by dissipating as heat the energy
absorbed in excess. Studies on NPQ have almost exclusively focused on photosystem
II (PSII), as it was believed that NPQ does not occur in photosystem I (PSI).
Recently, Ballottari et al. [Ballottari M, et al. (2014) Proc Natl Acad Sci USA
111:E2431-E2438], analyzing PSI particles isolated from an Arabidopsis thaliana
mutant that accumulates zeaxanthin constitutively, have reported that this
xanthophyll can efficiently induce chlorophyll fluorescence quenching in PSI. In
this work, we have checked the biological relevance of this finding by analyzing
WT plants under high-light stress conditions. By performing time-resolved
fluorescence measurements on PSI isolated from Arabidopsis thaliana WT in dark
adapted and high-light-stressed (NPQ) states, we find that the fluorescence
kinetics of both PSI are nearly identical. To validate this result in vivo, we
have measured the kinetics of PSI directly on leaves in unquenched and NPQ
states; again, no differences were observed. It is concluded that PSI does not
undergo NPQ in biologically relevant conditions in Arabidopsis thaliana The
possible role of zeaxanthin in PSI photoprotection is discussed.
PMID- 28416697
TI - Small molecule-mediated inhibition of myofibroblast transdifferentiation for the
treatment of fibrosis.
AB - Fibrosis, a disease in which excessive amounts of connective tissue accumulate in
response to physical damage and/or inflammatory insult, affects nearly every
tissue in the body and can progress to a state of organ malfunction and death. A
hallmark of fibrotic disease is the excessive accumulation of extracellular
matrix-secreting activated myofibroblasts (MFBs) in place of functional
parenchymal cells. As such, the identification of agents that selectively inhibit
the transdifferentiation process leading to the formation of MFBs represents an
attractive approach for the treatment of diverse fibrosis-related diseases.
Herein we report the development of a high throughput image-based screen using
primary hepatic stellate cells that identified the antifungal drug itraconazole
(ITA) as an inhibitor of MFB cell fate in resident fibroblasts derived from
multiple murine and human tissues (i.e., lung, liver, heart, and skin). Chemical
optimization of ITA led to a molecule (CBR-096-4) devoid of antifungal and human
cytochrome P450 inhibitory activity with excellent pharmacokinetics, safety, and
efficacy in rodent models of lung, liver, and skin fibrosis. These findings may
serve to provide a strategy for the safe and effective treatment of a broad range
of fibrosis-related diseases.
PMID- 28416698
TI - Selective in vivo removal of pathogenic anti-MAG autoantibodies, an antigen
specific treatment option for anti-MAG neuropathy.
AB - Anti-MAG (myelin-associated glycoprotein) neuropathy is a disabling autoimmune
peripheral neuropathy caused by monoclonal IgM autoantibodies that recognize the
carbohydrate epitope HNK-1 (human natural killer-1). This glycoepitope is highly
expressed on adhesion molecules, such as MAG, present in myelinated nerve fibers.
Because the pathogenicity and demyelinating properties of anti-MAG autoantibodies
are well established, current treatments are aimed at reducing autoantibody
levels. However, current therapies are primarily immunosuppressive and lack
selectivity and efficacy. We therefore hypothesized that a significant
improvement in the disease condition could be achieved by selectively
neutralizing the pathogenic anti-MAG antibodies with carbohydrate-based ligands
mimicking the natural HNK-1 glycoepitope 1. In an inhibition assay, a mimetic (2,
mimHNK-1) of the natural HNK-1 epitope blocked the interaction of MAG with
pathogenic IgM antibodies from patient sera but with only micromolar affinity.
Therefore, considering the multivalent nature of the MAG-IgM interaction,
polylysine polymers of different sizes were substituted with mimetic 2. With the
most promising polylysine glycopolymer PL84(mimHNK-1)45 the inhibitory effect on
patient sera could be improved by a factor of up to 230,000 per epitope,
consequently leading to a low-nanomolar inhibitory potency. Because clinical
studies indicate a correlation between the reduction of anti-MAG IgM levels and
clinical improvement, an immunological surrogate mouse model for anti-MAG
neuropathy producing high levels of anti-MAG IgM was developed. The observed
efficient removal of these antibodies with the glycopolymer PL84(mimHNK-1)45
represents an important step toward an antigen-specific therapy for anti-MAG
neuropathy.
PMID- 28416699
TI - IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis and X
ray crystallography.
AB - The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is an IP3-gated ion
channel that releases calcium ions (Ca2+) from the endoplasmic reticulum. The IP3
binding sites in the large cytosolic domain are distant from the Ca2+ conducting
pore, and the allosteric mechanism of how IP3 opens the Ca2+ channel remains
elusive. Here, we identify a long-range gating mechanism uncovered by channel
mutagenesis and X-ray crystallography of the large cytosolic domain of mouse type
1 IP3R in the absence and presence of IP3 Analyses of two distinct space group
crystals uncovered an IP3-dependent global translocation of the curvature alpha
helical domain interfacing with the cytosolic and channel domains. Mutagenesis of
the IP3R channel revealed an essential role of a leaflet structure in the alpha
helical domain. These results suggest that the curvature alpha-helical domain
relays IP3-controlled global conformational dynamics to the channel through the
leaflet, conferring long-range allosteric coupling from IP3 binding to the Ca2+
channel.
PMID- 28416700
TI - Intensifying postfire weather and biological invasion drive species loss in a
Mediterranean-type biodiversity hotspot.
AB - Prolonged periods of extreme heat or drought in the first year after fire affect
the resilience and diversity of fire-dependent ecosystems by inhibiting seed
germination or increasing mortality of seedlings and resprouting individuals.
This interaction between weather and fire is of growing concern as climate
changes, particularly in systems subject to stand-replacing crown fires, such as
most Mediterranean-type ecosystems. We examined the longest running set of
permanent vegetation plots in the Fynbos of South Africa (44 y), finding a
significant decline in the diversity of plots driven by increasingly severe
postfire summer weather events (number of consecutive days with high temperatures
and no rain) and legacy effects of historical woody alien plant densities 30 y
after clearing. Species that resprout after fire and/or have graminoid or herb
growth forms were particularly affected by postfire weather, whereas all species
were sensitive to invasive plants. Observed differences in the response of
functional types to extreme postfire weather could drive major shifts in
ecosystem structure and function such as altered fire behavior, hydrology, and
carbon storage. An estimated 0.5 degrees C increase in maximum temperature
tolerance of the species sets unique to each survey further suggests selection
for species adapted to hotter conditions. Taken together, our results show
climate change impacts on biodiversity in the hyperdiverse Cape Floristic Region
and demonstrate an important interaction between extreme weather and disturbance
by fire that may make flammable ecosystems particularly sensitive to climate
change.
PMID- 28416702
TI - Massive horizontal transfer of transposable elements in insects.
AB - Horizontal transfer (HT) of genetic material is central to the architecture and
evolution of prokaryote genomes. Within eukaryotes, the majority of HTs reported
so far are transfers of transposable elements (TEs). These reports essentially
come from studies focusing on specific lineages or types of TEs. Because of the
lack of large-scale survey, the amount and impact of HT of TEs (HTT) in eukaryote
evolution, as well as the trends and factors shaping these transfers, are poorly
known. Here, we report a comprehensive analysis of HTT in 195 insect genomes,
representing 123 genera and 13 of the 28 insect orders. We found that these
insects were involved in at least 2,248 HTT events that essentially occurred
during the last 10 My. We show that DNA transposons transfer horizontally more
often than retrotransposons, and unveil phylogenetic relatedness and geographical
proximity as major factors facilitating HTT in insects. Even though our study is
restricted to a small fraction of insect biodiversity and to a recent
evolutionary timeframe, the TEs we found to be horizontally transferred generated
up to 24% (2.08% on average) of all nucleotides of insect genomes. Together, our
results establish HTT as a major force shaping insect genome evolution.
PMID- 28416701
TI - Defective synaptic connectivity and axonal neuropathology in a human iPSC-based
model of familial Parkinson's disease.
AB - alpha-Synuclein (alphaSyn) is the major gene linked to sporadic Parkinson's
disease (PD), whereas the G209A (p.A53T) alphaSyn mutation causes a familial form
of PD characterized by early onset and a generally severe phenotype, including
nonmotor manifestations. Here we generated de novo induced pluripotent stem cells
(iPSCs) from patients harboring the p.A53T mutation and developed a robust model
that captures PD pathogenic processes under basal conditions. iPSC-derived mutant
neurons displayed novel disease-relevant phenotypes, including protein
aggregation, compromised neuritic outgrowth, and contorted or fragmented axons
with swollen varicosities containing alphaSyn and Tau. The identified
neuropathological features closely resembled those in brains of p.A53T patients.
Small molecules targeting alphaSyn reverted the degenerative phenotype under both
basal and induced stress conditions, indicating a treatment strategy for PD and
other synucleinopathies. Furthermore, mutant neurons showed disrupted synaptic
connectivity and widespread transcriptional alterations in genes involved in
synaptic signaling, a number of which have been previously linked to mental
disorders, raising intriguing implications for potentially converging disease
mechanisms.
PMID- 28416703
TI - On the Evolutionary Origin of CAM Photosynthesis.
PMID- 28416704
TI - Diurnal Variation in Gas Exchange: The Balance between Carbon Fixation and Water
Loss.
AB - Stomatal control of transpiration is critical for maintaining important
processes, such as plant water status, leaf temperature, as well as permitting
sufficient CO2 diffusion into the leaf to maintain photosynthetic rates (A).
Stomatal conductance often closely correlates with A and is thought to control
the balance between water loss and carbon gain. It has been suggested that a
mesophyll-driven signal coordinates A and stomatal conductance responses to
maintain this relationship; however, the signal has yet to be fully elucidated.
Despite this correlation under stable environmental conditions, the responses of
both parameters vary spatially and temporally and are dependent on species,
environment, and plant water status. Most current models neglect these aspects of
gas exchange, although it is clear that they play a vital role in the balance of
carbon fixation and water loss. Future efforts should consider the dynamic nature
of whole-plant gas exchange and how it represents much more than the sum of its
individual leaf-level components, and they should take into consideration the
long-term effect on gas exchange over time.
PMID- 28416705
TI - Defining the Diverse Cell Populations Contributing to Lignification in
Arabidopsis Stems.
AB - Many land plants evolved tall and sturdy growth habits due to specialized cells
with thick lignified cell walls: tracheary elements that function in water
transport and fibers that function in structural support. The objective of this
study was to define how and when diverse cell populations contribute lignin
precursors, monolignols, to secondary cell walls during lignification of the
Arabidopsis (Arabidopsis thaliana) inflorescence stem. Previous work demonstrated
that, when lignin biosynthesis is suppressed in fiber and tracheary element cells
with thickened walls, fibers become lignin-depleted while vascular bundles still
lignify, suggesting that nonlignifying neighboring xylem cells are contributing
to lignification. In this work, we dissect the contributions of different cell
types, specifically xylary parenchyma and fiber cells, to lignification of the
stem using cell-type-specific promoters to either knock down an essential
monolignol biosynthetic gene or to introduce novel monolignol conjugates.
Analysis of either reductions in lignin in knockdown lines, or the addition of
novel monolignol conjugates, directly identifies the xylary parenchyma and fiber
cell populations that contribute to the stem lignification and the developmental
timing at which each contribution is most important.
PMID- 28416706
TI - The GAN Exonuclease or the Flap Endonuclease Fen1 and RNase HII Are Necessary for
Viability of Thermococcus kodakarensis.
AB - Many aspects of and factors required for DNA replication are conserved across all
three domains of life, but there are some significant differences surrounding
lagging-strand synthesis. In Archaea, a 5'-to-3' exonuclease, related to both
bacterial RecJ and eukaryotic Cdc45, that associates with the replisome
specifically through interactions with GINS was identified and designated GAN
(for GINS-associated nuclease). Despite the presence of a well-characterized flap
endonuclease (Fen1), it was hypothesized that GAN might participate in primer
removal during Okazaki fragment maturation, and as a Cdc45 homologue, GAN might
also be a structural component of an archaeal CMG (Cdc45, MCM, and GINS)
replication complex. We demonstrate here that, individually, either Fen1 or GAN
can be deleted, with no discernible effects on viability and growth. However,
deletion of both Fen1 and GAN was not possible, consistent with both enzymes
catalyzing the same step in primer removal from Okazaki fragments in vivo RNase
HII has also been proposed to participate in primer processing during Okazaki
fragment maturation. Strains with both Fen1 and RNase HII deleted grew well. GAN
activity is therefore sufficient for viability in the absence of both RNase HII
and Fen1, but it was not possible to construct a strain with both RNase HII and
GAN deleted. Fen1 alone is therefore insufficient for viability in the absence of
both RNase HII and GAN. The ability to delete GAN demonstrates that GAN is not
required for the activation or stability of the archaeal MCM replicative
helicase.IMPORTANCE The mechanisms used to remove primer sequences from Okazaki
fragments during lagging-strand DNA replication differ in the biological domains.
Bacteria use the exonuclease activity of DNA polymerase I, whereas eukaryotes and
archaea encode a flap endonuclease (Fen1) that cleaves displaced primer
sequences. RNase HII and the GINS-associated exonuclease GAN have also been
hypothesized to assist in primer removal in Archaea Here we demonstrate that in
Thermococcus kodakarensis, either Fen1 or GAN activity is sufficient for
viability. Furthermore, GAN can support growth in the absence of both Fen1 and
RNase HII, but Fen1 and RNase HII are required for viability in the absence of
GAN.
PMID- 28416707
TI - Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in
Azospirillum brasilense Sp7.
AB - Chemotaxis is the movement of cells in response to gradients of diverse chemical
cues. Motile bacteria utilize a conserved chemotaxis signal transduction system
to bias their motility and navigate through a gradient. A central regulator of
chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with
membrane-bound receptors, which assemble into large polar arrays, to propagate
the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls
transient increases in swimming speed during chemotaxis, but it also biases the
cell length at division. However, the exact underlying molecular mechanisms for
Che1-dependent control of multiple cellular behaviors are not known. Here, we
identify specific domains of the CheA1 histidine kinase implicated in modulating
each of these functions. We show that CheA1 is produced in two isoforms: a
membrane-anchored isoform produced as a fusion with a conserved seven
transmembrane domain of unknown function (TMX) at the N terminus and a soluble
isoform similar to prototypical CheA. Site-directed and deletion mutagenesis
combined with behavioral assays confirm the role of CheA1 in chemotaxis and
implicate the TMX domain in mediating changes in cell length. Fluorescence
microscopy further reveals that the membrane-anchored isoform is distributed
around the cell surface while the soluble isoform localizes at the cell poles.
Together, the data provide a mechanism for the role of Che1 in controlling
multiple unrelated cellular behaviors via acquisition of a new domain in CheA1
and production of distinct functional isoforms.IMPORTANCE Chemotaxis provides a
significant competitive advantage to bacteria in the environment, and this
function has been transferred laterally multiple times, with evidence of
functional divergence in different genomic contexts. The molecular principles
that underlie functional diversification of chemotaxis in various genomic
contexts are unknown. Here, we provide a molecular mechanism by which a single
CheA protein controls two unrelated functions: chemotaxis and cell length.
Acquisition of this multifunctionality is seemingly a recent evolutionary event.
The findings illustrate a mechanism by which chemotaxis function may be co-opted
to regulate additional cellular functions.
PMID- 28416708
TI - PhoU Allows Rapid Adaptation to High Phosphate Concentrations by Modulating
PstSCAB Transport Rate in Sinorhizobium meliloti.
AB - Maintenance of cellular phosphate homeostasis is essential for cellular life. The
PhoU protein has emerged as a key regulator of this process in bacteria, and it
is suggested to modulate phosphate import by PstSCAB and control activation of
the phosphate limitation response by the PhoR-PhoB two-component system. However,
a proper understanding of PhoU has remained elusive due to numerous complications
of mutating phoU, including loss of viability and the genetic instability of the
mutants. Here, we developed two sets of strains of Sinorhizobium meliloti that
overcame these limitations and allowed a more detailed and comprehensive analysis
of the biological and molecular activities of PhoU. The data showed that phoU
cannot be deleted in the presence of phosphate unless PstSCAB is inactivated
also. However, phoU deletions were readily recovered in phosphate-free media, and
characterization of these mutants revealed that addition of phosphate to the
environment resulted in toxic levels of PstSCAB-mediated phosphate accumulation.
Phosphate uptake experiments indicated that PhoU significantly decreased the
PstSCAB transport rate specifically in phosphate-replete cells but not in
phosphate-starved cells and that PhoU could rapidly respond to elevated
environmental phosphate concentrations and decrease the PstSCAB transport rate.
Site-directed mutagenesis results suggested that the ability of PhoU to respond
to phosphate levels was independent of the conformation of the PstSCAB
transporter. Additionally, PhoU-PhoU and PhoU-PhoR interactions were detected
using a bacterial two-hybrid screen. We propose that PhoU modulates PstSCAB and
PhoR-PhoB in response to local, internal fluctuations in phosphate concentrations
resulting from PstSCAB-mediated phosphate import.IMPORTANCE Correct maintenance
of cellular phosphate homeostasis is critical in all kingdoms of life and in
bacteria involves the PhoU protein. This work provides novel insights into the
role of the Sinorhizobium meliloti PhoU protein, which plays a key role in rapid
adaptation to elevated phosphate concentrations. It is shown that PhoU rapidly
responds to elevated phosphate levels by significantly decreasing the phosphate
transport of PstSCAB, thereby preventing phosphate toxicity and cell death.
Additionally, a new model for phosphate sensing in bacterial species which
involves the PhoR-PhoB two-component system is presented. This work provides new
insights into the bacterial response to changing environmental conditions and
into regulation of the phosphate limitation response that influences numerous
bacterial processes, including antibiotic production and virulence.
PMID- 28416710
TI - Compliance with Uruguay's single presentation requirement.
AB - INTRODUCTION: Tobacco companies vary pack colours, designs, descriptors, flavours
and brand names on cigarette packs to target a multitude of consumers. These
different brand variants can falsely imply that some brand variants are less
harmful than others. Uruguay is the only country that requires cigarette
companies to adhere to a single presentation (one brand variant) per brand
family. METHODS: An existing, systematic pack purchasing protocol was adapted for
data collection. Neighbourhoods in Montevideo were categorised into five strata
by percentage of poor households. Five neighbourhoods within each stratum were
selected based on geographical variation. In each neighbourhood, a 'starting hub'
was identified and a systematic walking protocol was implemented to purchase
unique packs at four key vendor types. RESULTS: Unique packs were purchased in 9
out of 25 neighbourhoods. Fifty-six unique packs were purchased, representing 30
brands. Of these, 51 packs were legal, representing 26 brands. The majority of
the legal brands (n=16; 62%) were compliant with the requirement. The remaining
packs were non-compliant due to differences in colour, design element, brand
name, crest and descriptors. Although not prohibited by the single presentation
requirement, 16 legal brands had more than one stick count (10, 11, 14 or 20
sticks), and packs from four brands had more than one packaging type (hard, soft
or tin). CONCLUSION: Overall, compliance with Uruguay's single presentation
requirement was good. In addition to the current restrictions, future single
presentation requirements could expand to include packs in more than one stick
count and packaging type.
PMID- 28416712
TI - Comment on "A Database of Human Immune Receptor Alleles Recovered from Population
Sequencing Data".
PMID- 28416713
TI - Response to Comment on "A Database of Human Immune Receptor Alleles Recovered
from Population Sequencing Data".
PMID- 28416709
TI - Spheres of Hope, Packets of Doom: the Good and Bad of Outer Membrane Vesicles in
Interspecies and Ecological Dynamics.
AB - Outer membrane vesicles (OMVs) are proteoliposome nanoparticles ubiquitously
produced by Gram-negative bacteria. Typically bearing a composition similar to
those of the outer membrane and periplasm of the cells from which they are
derived, OMVs package an array of proteins, lipids, and nucleic acids. Once
considered inconsequential by-products of bacterial growth, OMVs have since been
demonstrated to mediate cellular stress relief, promote horizontal gene transfer
and antimicrobial activity, and elicit metazoan inflammation. Recently, OMVs have
gained appreciation as critical moderators of interorganismal dynamics. In this
review, we focus on recent progress toward understanding the functions of OMVs
with regard to symbiosis and ecological contexts, and we propose potential
avenues for future OMV studies.
PMID- 28416714
TI - JingleBells: A Repository of Immune-Related Single-Cell RNA-Sequencing Datasets.
AB - Recent advances in single-cell RNA-sequencing (scRNA-seq) technology increase the
understanding of immune differentiation and activation processes, as well as the
heterogeneity of immune cell types. Although the number of available immune
related scRNA-seq datasets increases rapidly, their large size and various
formats render them hard for the wider immunology community to use, and read
level data are practically inaccessible to the non-computational immunologist. To
facilitate datasets reuse, we created the JingleBells repository for immune
related scRNA-seq datasets ready for analysis and visualization of reads at the
single-cell level (http://jinglebells.bgu.ac.il/). To this end, we collected the
raw data of publicly available immune-related scRNA-seq datasets, aligned the
reads to the relevant genome, and saved aligned reads in a uniform format,
annotated for cell of origin. We also added scripts and a step-by-step tutorial
for visualizing each dataset at the single-cell level, through the commonly used
Integrated Genome Viewer (www.broadinstitute.org/igv/). The uniform scRNA-seq
format used in JingleBells can facilitate reuse of scRNA-seq data by
computational biologists. It also enables immunologists who are interested in a
specific gene to visualize the reads aligned to this gene to estimate cell
specific preferences for splicing, mutation load, or alleles. Thus JingleBells is
a resource that will extend the usefulness of scRNA-seq datasets outside the
programming aficionado realm.
PMID- 28416715
TI - T Cell-Transfer Experimental Autoimmune Encephalomyelitis: Pillar of Multiple
Sclerosis and Autoimmunity.
PMID- 28416716
TI - Pillars Article: The Rapid Isolation of Clonable Antigen-specific T Lymphocyte
Lines Capable of Mediating Autoimmune Encephalomyelitis. Eur J Immunol. 1981.11:
195-199.
PMID- 28416718
TI - Correction: Disruption of Nrf2 Impairs the Resolution of Hyperoxia-Induced Acute
Lung Injury and Inflammation in Mice.
PMID- 28416717
TI - Essential Neuroscience in Immunology.
AB - The field of immunology is principally focused on the molecular mechanisms by
which hematopoietic cells initiate and maintain innate and adaptive immunity.
That cornerstone of attention has been expanded by recent discoveries that
neuronal signals occupy a critical regulatory niche in immunity. The discovery is
that neuronal circuits operating reflexively regulate innate and adaptive
immunity. One particularly well-characterized circuit regulating innate immunity,
the inflammatory reflex, is dependent upon action potentials transmitted to the
reticuloendothelial system via the vagus and splenic nerves. This field has grown
significantly with the identification of several other reflexes regulating
discrete immune functions. As outlined in this review, the delineation of these
mechanisms revealed a new understanding of immunity, enabled a first-in-class
clinical trial using bioelectronic devices to inhibit cytokines and inflammation
in rheumatoid arthritis patients, and provided a mosaic view of immunity as the
integration of hematopoietic and neural responses to infection and injury.
PMID- 28416719
TI - Correction: Cutting Edge: Integrin alpha4 Is Required for Regulatory B Cell
Control of Experimental Autoimmune Encephalomyelitis.
PMID- 28416721
TI - Correction: A Database of Human Immune Receptor Alleles Recovered from Population
Sequencing Data.
PMID- 28416722
TI - Correction: Prevention of Vgamma9Vdelta2 T Cell Activation by a Vgamma9Vdelta2
TCR Nanobody.
PMID- 28416720
TI - Correction: Key Residues at Third CDR3beta Position Impact Structure and Antigen
Recognition of Human Invariant NK TCRs.
PMID- 28416723
TI - The origin of inner Solar System water.
AB - Of the potential volatile sources for the terrestrial planets, the CI and CM
carbonaceous chondrites are closest to the planets' bulk H and N isotopic
compositions. For the Earth, the addition of approximately 2-4 wt% of CI/CM
material to a volatile-depleted proto-Earth can explain the abundances of many of
the most volatile elements, although some solar-like material is also required.
Two dynamical models of terrestrial planet formation predict that the
carbonaceous chondrites formed either in the asteroid belt ('classical' model) or
in the outer Solar System (5-15 AU in the Grand Tack model). To test these
models, at present the H isotopes of water are the most promising indicators of
formation location because they should have become increasingly D-rich with
distance from the Sun. The estimated initial H isotopic compositions of water
accreted by the CI, CM, CR and Tagish Lake carbonaceous chondrites were much more
D-poor than measured outer Solar System objects. A similar pattern is seen for N
isotopes. The D-poor compositions reflect incomplete re-equilibration with H2 in
the inner Solar System, which is also consistent with the O isotopes of
chondritic water. On balance, it seems that the carbonaceous chondrites and their
water did not form very far out in the disc, almost certainly not beyond the
orbit of Saturn when its moons formed (approx. 3-7 AU in the Grand Tack model)
and possibly close to where they are found today.This article is part of the
themed issue 'The origin, history and role of water in the evolution of the inner
Solar System'.
PMID- 28416724
TI - On the attempts to measure water (and other volatiles) directly at the surface of
a comet.
AB - The Ptolemy instrument on the Philae lander (of the Rosetta space mission) was
able to make measurements of the major volatiles, water, carbon monoxide and
carbon dioxide, directly at the surface of comet 67P/Churyumov-Gerasimenko. We
give some background to the mission and highlight those instruments that have
already given insights into the notion of water in comets, and which will
continue to do so as more results are either acquired or more fully interpreted.
On the basis of our results, we show how comets may in fact be heterogeneous over
their surface, and how surface measurements can be used in a quest to comprehend
the daily cycles of processes that affect the evolution of comets.This article is
part of the themed issue 'The origin, history and role of water in the evolution
of the inner Solar System'.
PMID- 28416725
TI - The search for and analysis of direct samples of early Solar System aqueous
fluids.
AB - We describe the current state of the search for direct, surviving samples of
early, inner Solar System fluids-fluid inclusions in meteorites. Meteoritic
aqueous fluid inclusions are not rare, but they are very tiny and their
characterization is at the state of the art for most analytical techniques.
Meteoritic fluid inclusions offer us a unique opportunity to study early Solar
System brines in the laboratory. Inclusion-by-inclusion analyses of the trapped
fluids in carefully selected samples will, in the immediate future, provide us
detailed information on the evolution of fluids as they interacted with anhydrous
solid materials. Thus, real data can replace calculated fluid compositions in
thermochemical calculations of the evolution of water and aqueous reactions in
comets, asteroids, moons and the terrestrial planets.This article is part of the
themed issue 'The origin, history and role of water in the evolution of the inner
Solar System'.
PMID- 28416726
TI - D/H ratios of the inner Solar System.
AB - The original hydrogen isotope (D/H) ratios of different planetary bodies may
indicate where each body formed in the Solar System. However, geological and
atmospheric processes can alter these ratios through time. Over the past few
decades, D/H ratios in meteorites from Vesta and Mars, as well as from S- and C
type asteroids, have been measured. The aim of this article is to bring together
all previously published data from these bodies, as well as the Earth, in order
to determine the original D/H ratio for each of these inner Solar System
planetary bodies. Once all secondary processes have been stripped away, the inner
Solar System appears to be relatively homogeneous in terms of water D/H, with the
original water D/H ratios of Vesta, Mars, the Earth, and S- and C-type asteroids
all falling between deltaD values of -1000/00 and -5900/00. This homogeneity is
in accord with the 'Grand tack' model of Solar System formation, where giant
planet migration causes the S- and C-type asteroids to be mixed within 1 AU to
eventually form the terrestrial planets.This article is part of the themed issue
'The origin, history and role of water in the evolution of the inner Solar
System'.
PMID- 28416727
TI - Remotely distinguishing and mapping endogenic water on the Moon.
AB - Water and/or hydroxyl detected remotely on the lunar surface originates from
several sources: (i) comets and other exogenous debris; (ii) solar-wind
implantation; (iii) the lunar interior. While each of these sources is
interesting in its own right, distinguishing among them is critical for testing
hypotheses for the origin and evolution of the Moon and our Solar System.
Existing spacecraft observations are not of high enough spectral resolution to
uniquely characterize the bonding energies of the hydroxyl molecules that have
been detected. Nevertheless, the spatial distribution and associations of H, OH-
or H2O with specific lunar lithologies provide some insight into the origin of
lunar hydrous materials. The global distribution of OH-/H2O as detected using
infrared spectroscopic measurements from orbit is here examined, with particular
focus on regional geological features that exhibit OH-/H2O absorption band
strengths that differ from their immediate surroundings.This article is part of
the themed issue 'The origin, history and role of water in the evolution of the
inner Solar System'.
PMID- 28416728
TI - Global water cycle and the coevolution of the Earth's interior and surface
environment.
AB - The bulk Earth composition contains probably less than 0.3% of water, but this
trace amount of water can affect the long-term evolution of the Earth in a number
of different ways. The foremost issue is the occurrence of plate tectonics, which
governs almost all aspects of the Earth system, and the presence of water could
either promote or hinder the operation of plate tectonics, depending on where
water resides. The global water cycle, which circulates surface water into the
deep mantle and back to the surface again, could thus have played a critical role
in the Earth's history. In this contribution, we first review the present-day
water cycle and discuss its uncertainty as well as its secular variation. If the
continental freeboard has been roughly constant since the Early Proterozoic,
model results suggest long-term net water influx from the surface to the mantle,
which is estimated to be 3-4.5*1014 g yr-1 on the billion years time scale. We
survey geological and geochemical observations relevant to the emergence of
continents above the sea level as well as the nature of Precambrian plate
tectonics. The global water cycle is suggested to have been dominated by
regassing, and its implications for geochemical cycles and atmospheric evolution
are also discussed.This article is part of the themed issue 'The origin, history
and role of water in the evolution of the inner Solar System'.
PMID- 28416729
TI - The fate of water within Earth and super-Earths and implications for plate
tectonics.
AB - The Earth is likely to have acquired most of its water during accretion. Internal
heat of planetesimals by short-lived radioisotopes would have caused some water
loss, but impacts into planetesimals were insufficiently energetic to produce
further drying. Water is thought to be critical for the development of plate
tectonics, because it lowers viscosities in the asthenosphere, enabling
subduction. The following issue persists: if water is necessary for plate
tectonics, but subduction itself hydrates the upper mantle, how is the upper
mantle initially hydrated? The giant impacts of late accretion created magma
lakes and oceans, which degassed during solidification to produce a heavy
atmosphere. However, some water would have remained in the mantle, trapped within
crystallographic defects in nominally anhydrous minerals. In this paper, we
present models demonstrating that processes associated with magma ocean
solidification and overturn may segregate sufficient quantities of water within
the upper mantle to induce partial melting and produce a damp asthenosphere,
thereby facilitating plate tectonics and, in turn, the habitability of Earth-like
extrasolar planets.This article is part of the themed issue 'The origin, history
and role of water in the evolution of the inner Solar System'.
PMID- 28416730
TI - Early accretion of water and volatile elements to the inner Solar System:
evidence from angrites.
AB - Inner Solar System bodies are depleted in volatile elements relative to chondrite
meteorites, yet the source(s) and mechanism(s) of volatile-element depletion
and/or enrichment are poorly constrained. The timing, mechanisms and quantities
of volatile elements present in the early inner Solar System have vast
implications for diverse processes, from planetary differentiation to the
emergence of life. We report major, trace and volatile-element contents of a
glass bead derived from the D'Orbigny angrite, the hydrogen isotopic composition
of this glass bead and that of coexisting olivine and silicophosphates, and the
207Pb-206Pb age of the silicophosphates, 4568 +/- 20 Ma. We use volatile
saturation models to demonstrate that the angrite parent body must have been a
major body in the early inner Solar System. We further show via mixing
calculations that all inner Solar System bodies accreted volatile elements with
carbonaceous chondrite H and N isotope signatures extremely early in Solar System
history. Only a small portion (if any) of comets and gaseous nebular H species
contributed to the volatile content of the inner Solar System bodies.This article
is part of the themed issue 'The origin, history and role of water in the
evolution of the inner Solar System'.
PMID- 28416731
TI - The origin, history and role of water in the evolution of the inner Solar System.
PMID- 28416732
TI - Prevalence of kidney stones and associated risk factors in the Shunyi District of
Beijing, China.
AB - INTRODUCTION: Kidney stone formation is a multifactorial condition that involves
interaction of environmental and genetic factors. Presence of kidney stones is
strongly related to other diseases, which may result in a heavy economic and
social burden. Clinical data on the prevalence and influencing factors in kidney
stone disease in the north of China are scarce. In this study, we explored the
prevalence of kidney stone and potentially associated risk factors in the Shunyi
District of Beijing, China. METHODS: A population-based cross-sectional study was
conducted from December 2011 to November 2012 in a northern area of China.
Participants were interviewed in randomly selected towns. Univariate analysis of
continuous and categorical variables was first performed by calculation of
Spearman's correlation coefficient and Pearson Chi squared value, respectively.
Variables with statistical significance were further analysed by multivariate
logistic regression to explore the potential influencing factors. RESULTS: A
total of 3350 participants (1091 males and 2259 females) completed the survey and
the response rate was 99.67%. Among the participants, 3.61% were diagnosed with
kidney stone. Univariate analysis showed that significant differences were
evident in 31 variables. Blood and urine tests were performed in 100 randomly
selected patients with kidney stone and 100 healthy controls. Serum creatinine,
calcium, and uric acid were significantly different between the patients with
kidney stone and healthy controls. Multivariate logistic regression revealed that
being male (odds ratio=102.681; 95% confidence interval, 1.062-9925.797), daily
intake of white spirits (6.331; 1.204-33.282), and a history of urolithiasis
(1797.775; 24.228-133 396.982) were factors potentially associated with kidney
stone prevalence. CONCLUSIONS: Male gender, drinking white spirits, and a history
of urolithiasis are potentially associated with kidney stone formation.
PMID- 28416733
TI - Factors associated with multidisciplinary case conference outcomes in children
admitted to a regional hospital in Hong Kong with suspected child abuse: a
retrospective case series with internal comparison.
AB - INTRODUCTION: In all cases of suspected child abuse, accurate risk assessment is
vital to guide further management. This study examined the relationship between
risk factors in a risk assessment matrix and child abuse case conference
outcomes. METHODS: Records of all children hospitalised at United Christian
Hospital in Hong Kong for suspected child abuse from January 2012 to December
2014 were reviewed. Outcomes of the hospital abuse work-up as concluded in the
Multi-Disciplinary Case Conference were categorised as 'established', 'high
risk', or 'not established'. All cases of 'established' and 'high risk' were
included in the positive case conference outcome group and all cases of 'not
established' formed the comparison group. On the other hand, using the Risk
Assessment Matrix developed by the California State University, Fresno in 1990,
each case was allotted a matrix score of low, intermediate, or high risk in each
of 15 matrix domains, and an aggregate matrix score was derived. The effect of
individual matrix domain on case conference outcome was analysed. Receiver
operating characteristic curve analysis was used to examine the relationship
between case conference outcome and aggregate matrix score. RESULTS: In this
study, 265 children suspected of being abused were included, with 198 in the
positive case conference outcome group and 67 in the comparison group. Three
matrix domains (severity and frequency of abuse, location of injuries, and
strength of family support systems) were significantly associated with case
conference outcome. An aggregate cut-off score of 23 yielded a sensitivity of
91.4% and specificity of 38.2% in relation to outcome of abuse categorisation.
CONCLUSIONS: Risk assessment should be performed when handling suspected child
abuse cases. A high aggregate score should arouse suspicion in all disciplines
managing child abuse cases.
PMID- 28416734
TI - The angiotensin receptor blocker, Losartan, inhibits mammary tumor development
and progression to invasive carcinoma.
AB - Drugs that target the Renin-Angiotensin System (RAS) have recently come into
focus for their potential utility as cancer treatments. The use of Angiotensin
Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors
(ACEIs) to manage hypertension in cancer patients is correlated with improved
survival outcomes for renal, prostate, breast and small cell lung cancer.
Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is
linked to breast cancer pathogenesis, with unbiased analysis of gene-expression
studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in
ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no
evidence, so far, of the functional contribution of AT1R to breast tumorigenesis.
We explored the potential therapeutic benefit of ARB in a carcinogen-induced
mouse model of breast cancer and clarified the mechanisms associated with its
success.Mammary tumors were induced with 7,12-dimethylbenz[alpha]antracene (DMBA)
and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of
the ARB, Losartan treatment assessed in a preventative setting (n = 15 per
group). Tumor histopathology was characterised by immunohistochemistry, real-time
qPCR to detect gene expression signatures, and tumor cytokine levels measured
with quantitative bioplex assays. AT1R was detected with radiolabelled ligand
binding assays in fresh frozen tumor samples.We showed that therapeutic
inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor
burden; and no mammary tumor incidence in 20% of animals. We observed a
significant reduction in tumor progression from DCIS to invasive cancer with
Losartan treatment. This was associated with reduced tumor cell proliferation and
a significant reduction in IL-6, pSTAT3 and TNFalpha levels. Analysis of tumor
immune cell infiltrates, however, demonstrated no significant differences in the
recruitment of lymphocytes or tumour-associated macrophages in Losartan or
vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled
ligand binding assays in human breast cancer biopsies showed high AT1R levels in
30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA
database identified that high AT1R expression to be associated with luminal
breast cancer subtype.Our in vivo data and analysis of human invasive ductal
carcinoma samples identify the AT1R is a potential therapeutic target in breast
cancer, with the availability of a range of well-tolerated inhibitors currently
used in clinics. We describe a novel signalling pathway critical in breast
tumorigenesis, that may provide new therapeutic avenues to complement current
treatments.
PMID- 28416735
TI - Reciprocal control of lncRNA-BCAT1 and beta-catenin pathway reveals lncRNA-BCAT1
long non-coding RNA acts as a tumor suppressor in colorectal cancer.
AB - beta-catenin plays a major role in tumor development and progression. The present
study found that beta-catenin was upregulated in 30 samples of colorectal cancer
(CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non
coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets,
which were generated via the Affymetrix plus 2.0 microarray platform and
downloaded from the GEO database, revealed 20 differentially expressed lncRNAs
following beta-catenin knockdown. We focused on AK091631, a novel lncRNA, which
we named lncRNA-beta-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1
expression was decreased in CRC tissues, and was negatively associated with beta
catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression
suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and
MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell
growth and invasion via Wnt/beta-catenin pathway blockade, and that lncRNA-BCAT1
is repressed by Wnt/beta-catenin signaling. This evidence suggests that lncRNA
BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic
biomarker in CRC.
PMID- 28416736
TI - NOMO-1 gene is deleted in early-onset colorectal cancer.
AB - To characterize clinical features of a recurrent alteration in 16p13.12-p13.11 in
Colorectal Cancer (CRC), mainly in Early-onset subgroup (EOCRC), and to assess
the status of NOMO1, a gene located in that region, we analyzed differential
clinicopathological, familial and molecular features of CRC subsets with and
without alterations in the 16p13.12-p13.11, in global and EOCRC groups. We
confirmed the region by fluorescence in-situ hybridization, and Quantitative Real
Time PCR analyzed the status of NOMO1 in different age-of-onset and
Microsatellite Instability (MSI)-status CRC subsets. Both age-of-onset subsets
were subsequently extended to further confirm NOMO1 gene changes. 16p13.12-p13.11
alterations were observed in 23.3% of CRCs, and was detected more frequently in
EOCRC (33.3%) than in late-onset CRC (16.3%). The group with deletion in 16p
showed a higher frequency of females and left-colon locations; a better
prognosis; and higher Chromosomal Instability. Within the primary EOCRC
population, 34 out of 34 of tumours showed a homozygous deletion in NOMO1, while
in the late-onset population only 2 of the 17 tumours (11.7%) showed it. In the
extended group, we found 61 out of 75 EOCRC patients (81.3%) with homozygous
deletion and 7 patients (9.3%) with heterozygous deletion of NOMO1; moreover, in
the new 50 late-onset patients, the proportions of deletions decreased.
Microsatellite-Stable (MSS) EOCRC showed a very high proportion of homozygous
loss of NOMO1 (54 of 59 cases, 91.5%), while the deletion was observed in only 7
out of 16 MSI cases. Deletion of NOMO1 is a molecular marker predominantly
associated with EOCRC, particularly MSS subtypes.
PMID- 28416737
TI - Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired
resistance in human lung cancer cells with activating mutation of EGFR.
AB - PURPOSE: The aim of this work was to investigate the efficacy of sequential
treatment with first-, second- and third-generation epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired
resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL
DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors
by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer
(NSCLC) cell line harboring EGFR activating mutation, with a sequence of first
generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib),
of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal
antibody cetuximab, and of third-generation EGFR-TKI (osimertinib). RESULTS:
HCC827-derived xenografts and with acquired resistance to EGFR-inhibitors were
sensitive to the sequential use of first-, second- and third-generation EGFR
TKIs. Continuous EGFR inhibition of first-generation resistant tumors by
sequential treatment with afatinib plus/minus cetuximab, followed by osimertinib,
represented an effective therapeutic strategy in this model. Whereas T790M
resistance mutation was not detected, a major mechanism of acquired resistance
was the activation of components of the Hedgehog (Hh) pathway. This phenomenon
was accompanied by epithelial-to-mesenchymal transition. Cell lines established
in vitro from gefitinib-, or afatinib- or osimertinib-resistant tumors showed
metastatic properties and maintained EGFR-TKIs resistance in vitro, that was
reverted by the combined blockade of Hh, with the selective SMO inhibitor
sonidegib, and EGFR. CONCLUSIONS: EGFR-mutant NSCLC can benefit from continuous
treatment with EGFR-inhibitors, indepenently from mechanisms of resistance. In a
complex and heterogenous scenario, Hh showed an important role in mediating
resistance to EGFR-inhibitors through the induction of mesenchymal properties.
PMID- 28416738
TI - Differential expression of folate receptor 1 in medulloblastoma and the
correlation with clinicopathological characters and target therapeutic potential.
AB - Medulloblastoma is the most common malignant brain tumor in children. Folate
receptor 1 (Folr1) was abundantly expressed in some epithelial malignancies.
However the expression profile and the role of clinicopathological significance
and therapeutic target potential in medulloblastoma still remain elusive.
Currently we detected the expression of Folr1 in medulloblastoma and identified
the diagnostic application by evaluating the clinical, pathological and
neuroimaging values. Then we developed a target therapeutic compound with Folr1,
which exhibited promising efficiency in treatment of medulloblastoma. Folr1
expression was up-regulated in medulloblastoma and positively correlated with
percentage of Ki-67 and MMP9 labeling, pathological subtypes, serum Folr1 levels
and CSF spreading on MRI. The level of serum Folr1 showed rational sensitivity
and specificity in predicting histological subgroups. Strong Folr1 expression was
recommended as the independent value regarding the prognosis of patients with
medulloblastoma. Folr1 targeted therapy attenuated the tumor growth and
metastasis with down-regulation of MMPs proteins and activation of apoptosis.
Immunostaining analysis in the xenograft samples showed the decreased Ki-67 and
MMP9 index providing the strong evidences that Folr1 targeted application can
suppress the proliferation and invasion. Our findings uncovered in Folr1 a
predictive candidate and therapeutic target for medulloblastoma.
PMID- 28416739
TI - TKI rotation-induced persistent deep molecular response in multi-resistant blast
crisis of Ph+ CML.
AB - In chronic myeloid leukemia (CML) resistance against one or more BCR-ABL1
tyrosine kinase inhibitors (TKI) remains a clinical challenge. Preclinical data
suggest that TKI combinations may overcome resistance. We report on a heavily pre
treated 78 year-old female patient with CML who developed multi-resistant blast
crisis with bone marrow fibrosis and a Ph- clone. Treatment with ponatinib
resulted in blast cell clearance, decrease in fibrosis, and disappearance of BCR
ABL1, but also in severe thrombocytopenia with bleedings requiring platelet
transfusions. We therefore switched from ponatinib to bosutinib. During
bosutinib, platelet counts recovered. However, after 6 months, BCR-ABL1 mRNA
levels increased to > 1%. Therefore, we 'switched back' to ponatinib, and this
was again followed by disappearance of BCR-ABL1 and a decrease in platelets.
During the next 2 years, we applied ponatinib and bosutinib in continuous
rotation-cycles and added hydroxyurea in order to suppress all sub-clones and to
balance between efficacy and potential side effects following the principle of
personalized medicine. With this approach the patient remained in complete
molecular response and reached normal blood counts and a normal quality of life
without vascular or other side effects. In conclusion, TKI rotation is a novel
potent approach to suppress multiple resistant sub-clones and to balance between
clinical efficacy and side effects in patients with advanced CML. Clinical trials
are now warranted to show that TKI-rotation is in general safe and effective in
these patients.
PMID- 28416740
TI - Multi-targeting therapeutic mechanisms of the Chinese herbal medicine QHD in the
treatment of non-alcoholic fatty liver disease.
AB - Beneficial effects of the Chinese herbal medicine Qushi Huayu Decoction (QHD)
were observed with non-alcoholic fatty liver disease (NAFLD) patients and animal
models. The impact of QHD or its active components (geniposide and chlorogenic
acid, GC) on NAFLD liver transcriptome and gut microbiota was examined with NAFLD
rats. Increased expression for genes required for glutathione production and
decreased expression for genes required for lipid synthesis was observed in NAFLD
livers treated with QHD and GC. GC treatment decreased serum LPS, which could be
explained by reduced mucosal damage in the colon of GC-treated rats. Further, our
data suggest an increased abundance of Treg-inducing bacteria that stimulated the
Treg activity in GC treated colon, which in turn down-regulated inflammatory
signals, improved gut barrier function and consequently reduced hepatic exposure
to microbial products. Our study suggests that QHD simultaneously enhanced the
hepatic anti-oxidative mechanism, decreased hepatic lipid synthesis, and promoted
the regulatory T cell inducing microbiota in the gut.
PMID- 28416741
TI - Relaxin abrogates renal interstitial fibrosis by regulating macrophage
polarization via inhibition of Toll-like receptor 4 signaling.
AB - Renal fibrosis is a common feature of chronic kidney disease (CKD). To inhibit
the CKD process, it is important to prevent renal fibrosis, though CKD remains
incurable. Renal fibrosis can be inhibited by relaxin in several experimental
models, but the mechanism of relaxin for antifibrotic potential is still not
clear. And here we have studied the role of relaxin in macrophage polarization
and renal inflammation after unilateral ureteral obstruction (UUO). Our results
show that relaxin can downregulate the Toll-like receptor (TLR) 4 signaling,
shift macrophage polarization toward the M2 phenotype and ameliorat renal
fibrosis in the early stages of UUO. In vitro experiments, it has been confirmed
that relaxin can downregulate the TLR4 signaling and induce the M2 macrophage
transition. Furthermore, the transitional actions of macrophage phenotype induced
by relaxin are significantly blocked by TAK-242, a TLR4 antagonist, in vitro
experiments. Thus, there is a novel mechanism of relaxin for antifibrosis that
shifts macrophage polarization toward the M2 phenotype via inhibition of TLR4
signaling.
PMID- 28416742
TI - Model driven optimization of antiangiogenics + cytotoxics combination:
application to breast cancer mice treated with bevacizumab + paclitaxel doublet
leads to reduced tumor growth and fewer metastasis.
AB - Bevacizumab is the first-in-class antiangiogenic drug and is almost always
administrated in combination with cytotoxics. Reports have shown that bevacizumab
could induce a transient phase of vascular normalization, thus ensuring a better
drug delivery when cytotoxics administration is adjuvant. However, determining
the best sequence remains challenging. We have developed a mathematical model
describing the impact of antiangiogenics on tumor vasculature. A 3.4 days gap
between bevacizumab and paclitaxel was first proposed by our model. To test its
relevance, 84 mice were orthotopically xenografted with human MDA-231Luc+
refractory breast cancer cells. Two sets of experiments were performed, based
upon different bevacizumab dosing (10 or 20 mg/kg) and inter-cycle intervals (7
or 10 days), comprising several combinations with paclitaxel. Results showed that
scheduling bevacizumab 3 days before paclitaxel improved antitumor efficacy (48%
reduction in tumor size compared with concomitant dosing, p < 0.05) and reduced
metastatic spreading. Additionally, bevacizumab alone could lead to more
aggressive metastatic disease with shorter survival in animals. Our model was
able to fit the experimental data and provided insights on the underlying
dynamics of the vasculature's ability to deliver the cytotoxic agent. Final
simulations suggested a new, data-informed optimal gap of 2.2 days. Our
experimental data suggest that current concomitant dosing between bevacizumab and
paclitaxel could be a sub-optimal strategy at bedside. In addition, this proof of
concept study suggests that mathematical modelling could help to identify the
optimal interval among a variety of possible alternate treatment modalities, thus
refining the way experimental or clinical studies are conducted.
PMID- 28416743
TI - The urokinase plasminogen activation system in gastroesophageal cancer: A
systematic review and meta-analysis.
AB - BACKGROUND: The urokinase plasminogen activation (uPA) system is a crucial
pathway for tumour invasion and establishment of metastasis. Although there is
good evidence that uPA system expression is a clinically relevant biomarker in
some solid tumours, its role in gastroesophageal cancer is uncertain. RESULTS: We
identified 22 studies encompassing 1966 patients which fulfilled the inclusion
criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high
risk clinicopathological features. High uPA expression is associated with a
shorter RFS (HR 1.90 95% 1.16-3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74-2.80, p
< 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82
2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96
96% CI 1.07-3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28-2.64, p < 0.0001). There
was no significant association between PAI-2 expression and OS (HR 0.97 95%CI
0.48-1.94, p < 0.92) although data was limited. MATERIALS AND METHODS: We
undertook a systematic review evaluating expression of uPA, urokinase plasminogen
activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and
plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro
oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis
of clinicopathological associations, overall survival (OS) and recurrence free
survival (RFS). CONCLUSIONS: We conclude that the uPA system is a clinically
relevant biomarker in primary gastroesophageal cancer, with higher expression of
uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis.
This also highlights the potential utility of the uPA system as a therapeutic
target for improved treatment strategies.
PMID- 28416744
TI - Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for
intraoperative visualization of multiple cancer types.
AB - Incomplete resections and damage to critical structures increase morbidity and
mortality of patients with cancer. Targeted intraoperative fluorescence imaging
aids surgeons by providing real-time visualization of tumors and vital
structures. This study evaluated the tumor-targeted zwitterionic near-infrared
fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple
cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and
colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic
mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19)
tumors. Dose-ranging studies, including doses of 0.25, 1.0, 10, and 30 nmol, in
xenograft tumor models suggest an optimal dose of 10 nmol, corresponding to a
human equivalent dose of 63 MUg/kg, and an optimal imaging window between 2 and
24 h post-injection. The mean half-life of cRGD-ZW800-1 in blood was 25 min.
Biodistribution at 4 h showed the highest fluorescence signals in tumors and
kidneys. In vitro and in vivo competition experiments showed significantly lower
fluorescence signals when U-87 MG cells (minus 36%, p = 0.02) or HT-29 tumor
bearing mice (TBR at 4 h 3.2 +/- 0.5 vs 1.8 +/- 0.4, p = 0.03) were
simultaneously treated with unlabeled cRGD. cRGD-ZW800-1 visualized in vivo all
colorectal, breast, pancreatic, and oral tumor xenografts in mice. Screening for
off-target interactions, cRGD-ZW800-1 showed only inhibition of COX-2, likely due
to binding of cRGD-ZW800-1 to integrin alphaVbeta3. Due to its recognition of
various integrins, which are expressed on malignant and neoangiogenic cells, it
is expected that cRGD-ZW800-1 will provide a sensitive and generic tool to
visualize cancer during surgery.
PMID- 28416745
TI - Stable H3 peptide was delivered by gold nanorods to inhibit LSD1 activation and
induce human mesenchymal stem cells differentiation.
AB - Recently, lysine-specific demethylase 1 (LSD1), which is the first identified
histone demethylase, regulates post-translational modifications and has great
promise as new targets for cancer and other diseases. Moreover, the ability of
LSD1 to induce the differentiation of stem cells has attracted great attention in
biological fields. In this study, we designed LSD1 peptide inhibitor based on its
substrate H3 peptide. Through introducing a disulfide bond to stabilize the
native peptide into alpha helical structure, we get a peptide with higher cell
permeability and stability compared to its parent form. Using gold nanorods
(AuNRs) as delivery systems to deliver stable peptide into human MSCs, the
delivery efficiency has been enhanced significantly by flow cytometry and cell
fluorescent imaging. The intracellular delivery of stable peptide by AuNRs-PEI
based nanocarriers could inhibit the activation of LSD1, which together with
hepatocyte growth factor (HGF) exhibits obviously synergistic effect to induce
human MSCs differentiation. Furthermore, the hepatic marker genes AFP (alpha
fetal protein) and ck19 are up-regulated by AuNRs-stable peptide (AuNRs- SP- PEI)
with HGF. In conclusion, our study is the first time to use stable H3 peptide to
inhibit LSD1 activation, which has been further delivered by AuNRs as
nanocarriers into human MSCs.
PMID- 28416747
TI - The TERT promoter mutation incidence is modified by germline TERT rs2736098 and
rs2736100 polymorphisms in hepatocellular carcinoma.
AB - Telomerase activation via induction of the catalytic component telomerase reverse
transcriptase (TERT) plays essential roles in malignant transformation. TERT
promoter-activating mutations were recently identified as a novel mechanism to
activate telomerase in hepatocellular carcinoma (HCC) and many other
malignancies. In addition, single nucleotide polymorphisms (SNPs) in the TERT
rs2736098 and rs2736100 are significantly associated with cancer susceptibility.
It is currently unclear whether different germline TERT variants modify TERT
promoter mutations. Here we analyzed the TERT promoter status and genotyped the
TERT SNPs at rs2736098 and rs2736100 in patients with HCC. Thirty percent of HCCs
harbored TERT promoter mutations and there was a significant difference in
rs2736098 and rs2736100 genotypes between wt and mutant TERT promoter-bearing HCC
tumors (P = 0.007 and 0.018, respectively). For rs2736100, the cancer risk
genotype CC was significantly associated with a reduced incidence of TERT
promoter mutations compared to AA + AC variants [Odds ratio (OR): 0.181, 95%
Confidence interval (CI): 0.0543-0.601, P = 0.004]. The rs2736098_CT genotype was
significantly associated with the TERT promoter mutation-positive tumors compared
to the TT genotype (OR: 5.391, 95% CI: 1.234-23.553, P = 0.025). These
differences in genotype distribution did not differ between patients with a wt
TERT promoter and controls. The presence of TERT promoter mutations was not
associated with clinico-pathological variables. Taken together, the germline TERT
genetic background may significantly affect the onset of TERT promoter mutations
in HCCs, which provides a better understanding of HCC-related TERT promoter
mutations and telomerase regulation in cancer.
PMID- 28416748
TI - Differential expression of M3 muscarinic receptors in progressive colon neoplasia
and metastasis.
AB - M3 muscarinic receptor (M3R) activation promotes colon cancer cell proliferation,
migration, and invasion in vitro. Although over-expression of CHRM3, the gene
encoding M3R, is reported in primary colon cancers, expression of M3R itself has
not been studied in colon neoplasia. We compared M3R expression in normal colon
to colon adenomas, and primary and metastatic colon cancers. Compared to adjacent
normal colon, CHRM3 expression was increased up to 128-fold in 10 of 18
consecutive surgical cancer specimens (56%) and associated with metastatic spread
(P < 0.05). To analyze M3R protein expression we interrogated 29 consecutive
paraffin-embedded colon adenocarcinomas and adjacent normal colon using a
specific anti-M3R antibody and immunoperoxidase staining. This revealed weak M3R
expression in normal colonocytes, primarily on basolateral surfaces. In contrast,
in 25 of 29 cancer tissues (86%) we observed both cytoplasmic and plasma membrane
over-expression of M3R; compared to normal epithelium, mean M3R staining
intensity was increased more than two-fold in colon cancer (P < 0.001). M3R
staining was also increased in 22 colon adenomas compared to adjacent normal
colon (P < 0.001). In contrast, M3R staining intensity was not increased in lymph
node or liver metastases. These findings suggest M3R expression plays an
important role in early progression and invasion of colon neoplasia but is less
important once tumors have spread.
PMID- 28416750
TI - Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition
in human gastric cancer cells in vitro.
AB - BACKGROUND: Gastric cancer (GC) is a global health problem because of limited
treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported
to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its
effects on GC remains largely unknown. Notch signaling plays a critical role in
cell proliferation, differentiation and apoptosis. Therefore, it may contribute
to the development of GC. This study aims to explore the role of Notch2 in ACGs'
activities in GC cells. RESULTS: ACGs inhibited GC cells' viability in a dose
dependent manner and led to cell apoptosis and cell cycle arrest in G0/G1 phase
with an increased Notch2 expression. Additionally, Notch2 siRNA reduced ACGs
induced cell growth inhibition while Notch2 cDNA transfection did the opposite.
MATERIALS AND METHODS: ACGs were administrated in GC cells and cell proliferation
was assayed by MTS, cell apoptosis and cell cycle were detected by flow
cytometry. Additionally, the expression of Notch2 and the downstream target Hes1
were identified by Western blot. Furthermore, Notch2-siRNA transfection and
Notch2-cDNA were performed to investigate the role of Notch2 in the antitumor
effect of ACGs. CONCLUSIONS: Up-regulation of Notch2 by ACGs is a potential
therapeutic strategy for GC.
PMID- 28416751
TI - Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest
in AML in vitro and prolongs survival in vivo.
AB - Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and
ineligible to undergo intensive treatment, have a dismal prognosis. The small
molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like
kinase 1 and has shown remarkable anti-leukemic activity when combined with low
dose cytarabine. We have demonstrated that AML cells are highly vulnerable to
cell death in mitosis yet manage to escape a mitotic block through mitotic
slippage by sustained proteasome-dependent slow degradation of cyclin B.
Therefore, we tested whether interfering with mitotic slippage through proteasome
inhibition arrests and kills AML cells more efficiently during mitosis. We show
that therapeutic doses of bortezomib block the slow degradation of cyclin B
during a volasertib-induced mitotic arrest in AML cell lines and patient-derived
primary AML cells. In a xenotransplant mouse model of human AML, mice receiving
volasertib in combination with bortezomib showed superior disease control
compared to mice receiving volasertib alone, highlighting the potential
therapeutic impact of this drug combination.
PMID- 28416752
TI - CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma.
AB - The aim of this meta-analysis was to evaluate the association between cyclin
dependent kinase Inhibitor-2B (CDKN2B) gene rs1063192 polymorphism and glaucoma
risk. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs)
and 95% confidence intervals (CIs) were calculated by using fixed-effect or
random-effect models. A total of 14 case-control studies involving 11,316 cases
and 24,055 controls were included. Meta-analysis showed that CDKN2B gene
rs1063192 polymorphism was associated with a decreased risk of glaucoma.
Stratification analysis of ethnicity indicated that rs1063192 polymorphism
decreased the risk of glaucoma among Caucasians and Asians. Stratification
analysis by type of glaucoma revealed that rs1063192 polymorphism conferred a
protective factor of primary open-angle glaucoma (POAG) and non-POAG.
Stratification by source of controls uncovered an association between rs1063192
polymorphism and glaucoma in groups of population-based controls. In conclusion,
this meta-analysis indicates that CDKN2B gene rs1063192 polymorphism is
significantly associated with a decreased risk of glaucoma.
PMID- 28416753
TI - Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the
growth inhibitor lycorine in a mouse model of renal cell carcinoma.
AB - Renal cell carcinoma (RCC) management has undergone a major transformation over
the past decade; immune checkpoint inhibitors are currently undergoing clinical
trials and show promising results. However, the effectiveness of immune
checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited.
Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is
touted as a potential anti-cancer drug because of its demonstrative growth
inhibition capacity (induction of cell cycle arrest and inhibition of
vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy
with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4)
has improved outcomes in cancer patients. However, the anti-tumor efficacy of
combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated
a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine
RCC model. As a means of in vitro confirmation, we found that lycorine
hydrochloride inhibited the viability of various RCC cell lines. Furthermore,
luciferase-expressing Renca cells were implanted in the left kidney and the lung
of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride
and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and
luciferin-staining in tumor images. Importantly, the observed anti-tumor effects
of this combination were dependent on significantly suppressing regulatory T
cells while upregulating effector T cells; a decrease in regulatory T cells by
31.43% but an increase in effector T cells by 31.59% were observed in the
combination group compared with those in the control group). We suggest that a
combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic
option for RCC patients.
PMID- 28416755
TI - Efficacy and safety of BRAF inhibition alone versus combined BRAF and MEK
inhibition in melanoma: a meta-analysis of randomized controlled trials.
AB - Recent clinical studies have shown that combination therapy of BRAF and MEK
inhibition provides more survival benefit than BRAF inhibition monotherapy.
However, the adverse events due to BRAF and MEK inhibitors impact the physical
comfort and social life of patients. Thus, in this study we have undertaken a
meta-analysis of randomized controlled trials to compare the efficacy and adverse
events risk between monotherapy and combination therapy. We identified the
relevant studies by searching PubMed, EMBASE and Google scholar databases,
between the year January 2000 and May 2016. Based on the heterogeneity, the fixed
or random-effects models were employed to analyze the efficacy and the incidence
rate of adverse events. In addition, the subgroup analyses were conducted to
overcome the effects of heterogeneity. Finally, our study included five RCTs,
involving 1730 patients for this meta-analysis. The fixed-effects model
demonstrated that combination therapy of BRAF and MEK inhibition provided more
survival benefit in terms of ORR, PFS and OS (P < 0.00001). But, the combination
therapy also significantly increased the incidences of pyrexia, chills, vomiting,
chorioretinopathy, retinal detachment, hypertension, night sweats, increased
aspartate aminotransferase and creatine kinase levels (P < 0.05) as compared to
monotherapy. But, based on the significantly better survival outcomes, the
combined BRAF and MEK inhibition will obviously be the mainstay therapy for the
BRAF V600-mutant melanoma. However, a set of adverse events should be paid
attention when physicians consider combination therapy.
PMID- 28416756
TI - Prognostic significance of ZEB1 and ZEB2 in digestive cancers: a cohort-based
analysis and secondary analysis.
AB - BACKGROUND: Digestive cancers are common malignancies worldwide, however there
are few effective prognostic markers available. In this study we comprehensively
investigated the prognostic significance of ZEB1 and ZEB2 in digestive cancers.
METHODS: Electronic databases were searched and studies met the selection
criteria were included. Study information was recorded and quality assessment was
performed according to the REMARK guideline. Hazard ratios and its corresponding
95% confidence intervals were extracted and pooled. Sensitivity analyses,
subgroup analyses, cumulative meta-analyses and secondary analyses were also
performed to increase the stability and reliability of our results. RESULTS: 24
cohort studies were included in the study. High ZEB1 and ZEB2 levels predicted
poor overall survival, meanwhile high ZEB2 levels predicted poor disease free
survival for digestive cancer patients. From subgroup analyses we observed ZEB1
was found to be significantly associated with poor overall survival for patients
with pancreatic cancer, gastric cancer and colorectal cancer, while ZEB2 was
found to be significantly associated with poor overall survival for patients with
hepatocellular carcinoma and gastric cancer. Furthermore, by conducting secondary
analyses we confirmed both ZEB1 and ZEB2 played important roles in gastric cancer
prediction. In addition, we found high ZEB1 and ZEB2 expression were
significantly associated with depth of invasion, lymph node metastasis and TNM
stage in digestive cancer patients. CONCLUSIONS: The present study validated the
prognostic value and clinicopathological association of ZEB1 and ZEB2 in
digestive cancers, especially in gastric cancer.
PMID- 28416757
TI - Theranostic imaging of liver cancer using targeted optical/MRI dual-modal probes.
AB - The accurate preoperative detection and intraoperative navigation afforded by
imaging techniques have had significant impact on the success of liver cancer
surgeries. However, it is difficult to achieve satisfactory performance in both
diagnosis and surgical treatment processes using any single modality imaging
method. Here, we report the synthesis and characteristics of a novel dual
modality magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF)
probe and verify its feasibility in nude mouse models with liver cancer. The
probes are comprised of superparamagnetic iron oxide (SPIO) nanoparticles coated
with liposomes to which a tumor-targeted agent, Arg-Gly-Asp peptides (RGD), and a
NIRF dye (indocyanine green, ICG) have been conjugated. Specific targeting,
biodistribution, and the imaging ability of the probes for MRI-NIRF were
examined. Furthermore, we applied the dual-modality methodology toward the
preoperative diagnosis and intraoperative guidance of radical resection in mouse
models with both orthotopic liver tumors and intrahepatic tumor metastasis. The
study demonstrated that both MRI and fluorescent images showed clear tumor
delineation after probe injection (SPIO@Liposome-ICG-RGD). The contrast-to-noise
ratio obtained from MRI was 31.9 +/- 25.4 at post-injection for the preoperative
diagnosis, which is helpful for detecting small tumors (0.9 +/- 0.5 mm). The
maximum tumor to background ratio of NIRF imaging was 2.5 +/- 0.3 at 72 h post
injection for effectively capturing miniscule tumor lesions (0.6 +/- 0.3 mm)
intraoperatively. The novel MRI-NIRF dual modality probes are promising for the
achievement of more accurate liver tumor detection and resection.
PMID- 28416758
TI - Synergistic interactions between PLK1 and HDAC inhibitors in non-Hodgkin's
lymphoma cells occur in vitro and in vivo and proceed through multiple
mechanisms.
AB - Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the
histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B
cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo.
Exposure of DLBCL cells to very low concentrations of volasertib in combination
with belinostat synergistically increased cell death (apoptosis). Similar
interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib
resistant cells and primary lymphoma cells. Co-exposure to volasertib/belinostat
induced a marked increase in M-phase arrest, phospho-histone H3, mitotic errors,
cell death in M-phase, and DNA damage. Belinostat diminished c-Myc mRNA and
protein expression, an effect significantly enhanced by volasertib co-exposure. c
Myc knock-down increased DNA damage and cell death in response to volasertib,
arguing that c-Myc down-regulation plays a functional role in the lethality of
this regimen. Notably, PLK1 knock-down in DLBCL cells significantly increased
belinostat-induced M-phase accumulation, phospho-histone H3, gammaH2AX, and cell
death. Co-administration of volasertib and belinostat dramatically reduced tumor
growth in an ABC-DLBCL flank model (U2932) and a systemic double-hit lymphoma
model (OCI-Ly18), accompanied by a pronounced increase in survival without
significant weight loss or other toxicities. Together, these findings indicate
that PLK1/HDAC inhibition warrants attention as a therapeutic strategy in NHL.
PMID- 28416760
TI - The histone demethylase KDM3A regulates the transcriptional program of the
androgen receptor in prostate cancer cells.
AB - The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional
networks in a variety of biological processes such as spermatogenesis,
metabolism, stem cell activity, and tumor progression. We matched transcriptomic
and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic
control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring
histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation
effects of KDM3A. Combined assessment of histone demethylation events and gene
expression changes presented major transcriptional activation suggesting that
distinct oncogenic regulators may synergize with the epigenetic patterns by
KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized
androgen signaling indicating that KDM3A plays a key role in regulating androgen
receptor activity. Matched ChIP-Seq and knockdown experiments of KDM3A in
combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9
methylation marks around androgen receptor binding sites of selected
transcriptional targets in androgen signaling including positive regulation of
KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1,
IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of
KDM3A-dependent genes identifies an epigenetic and transcriptional network in
androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP
Seq data highlights specific gene targets and the ability of epigenetic master
regulators to control oncogenic pathways and cancer progression.
PMID- 28416761
TI - Oncogenic senescence: a multi-functional perspective.
AB - Cellular senescence is defined as an irreversible growth arrest with the
acquisition of a distinctive secretome. The growth arrest is a potent anticancer
mechanism whereas the secretome facilitates wound healing, tissue repair, and
development. The senescence response has also become increasingly recognized as
an important contributor to aging and age-related diseases, including cancer.
Although oncogenic mutations are capable of inducing a beneficial senescence
response that prevents the growth of premalignant cells and promotes cancer
immune-surveillance, the secretome of senescent cells also includes factors with
pro-tumorigenic properties. On June 23rd and 24th, 2016, the Division of Cancer
Biology of the National Cancer Institute sponsored a workshop to discuss the
complex role of cellular senescence in tumorigenesis with the goal to define the
major challenges and opportunities within this important field of cancer
research. Additionally, it was noted how the development of novel tools and
technologies are required to accelerate research into a mechanistic understanding
of senescent cells in carcinogenesis in order to overcome the current limitations
in this exciting, yet ill-defined area.
PMID- 28416762
TI - Role of CD152 genetic polymorphisms in the susceptibility to breast cancer.
AB - BACKGROUND: The polymorphisms in cluster of differentiation 152 (CD152) gene have
been reported to be associated with breast cancer (BC), but relevant findings
were far from conclusive. Therefore, we carried out this meta-analysis to combine
those results for a clearer perspective on this issue. RESULTS: In our meta
analysis, a total of 8 eligible publications of 19 case-control studies were
selected, which totally contained 7,442 BC cases and 7,376 normal controls. Among
the five polymorphisms of CD152 gene, +49 G/A, -1661 A/G and -318 C/T
significantly increased the risk of BC under corresponding genetic comparisons;
while CT60 G/A polymorphism was negatively related to the cancer susceptibility.
In addition, -1772 T/C polymorphism of CD152 gene was not associated with the
development of BC. MATERIALS AND METHODS: Online databases and other sources were
searched for published studies on the relationship between BC susceptibility and
CD152 polymorphisms (+49 G/A, -1661 A/G, -1722 T/C, -318 C/T and CT60 G/A). The
strength of association was evaluated with pooled odds ratios (ORs) and their
corresponding 95% confidence intervals (95% CIs). Heterogeneity evaluation was
conducted via Q test. Sensitivity analysis was used to detect the stability of
our results. Begg's funnel plot and Egger's test were applied to investigate
publication bias among selected studies. CONCLUSIONS: The polymorphisms +49 G/A,
1661 A/G and -318 C/T may elevate the susceptibility to BC, but the polymorphism
CT60 G/A may offer protection against the cancer.
PMID- 28416759
TI - Beyond cell-cell adhesion: Plakoglobin and the regulation of tumorigenesis and
metastasis.
AB - Plakoglobin (also known as gamma-catenin) is a member of the Armadillo family of
proteins and a paralog of beta-catenin. Plakoglobin is a component of both the
adherens junctions and desmosomes, and therefore plays a vital role in the
regulation of cell-cell adhesion. Similar to beta-catenin, plakoglobin is capable
of participating in cell signaling in addition to its role in cell-cell adhesion.
In this context, beta-catenin has a well-documented oncogenic potential as a
component of the Wnt signaling pathway. In contrast, while some studies have
suggested a tumor promoting activity of plakoglobin in a cell/malignancy specific
context, it generally acts as a tumor/metastasis suppressor. How plakoglobin acts
as a growth/metastasis inhibitory protein has remained, until recently, unclear.
Recent evidence suggests that plakoglobin may suppress tumorigenesis and
metastasis by multiple mechanisms, including the suppression of oncogenic
signaling, interactions with various proteins involved in tumorigenesis and
metastasis, and the regulation of the expression of genes involved in these
processes. This review is primarily focused on various mechanisms by which
plakoglobin may inhibit tumorigenesis and metastasis.
PMID- 28416763
TI - Hormone receptor expression profiles differ between primary and recurrent high
grade serous ovarian cancers.
AB - Hormone receptor status assessment is necessary for selecting cancer patients who
might potentially benefit from endocrine therapy. To determine whether hormone
receptor status changes during tumor progression, we retrospectively examined 107
high-grade serous ovarian cancer (HGSC) patients with paired primary and
recurrent tumor specimens. Hormone receptor expression discordance rates between
primary and recurrent tumors were as follows: estrogen receptor (ER) 34.9%,
progesterone receptor (PR) 12.4%, androgen receptor (AR) 41.7%, follicle
stimulating hormone receptor 46.6%, luteinizing hormone receptor 50.5%, and
gonadotropin releasing hormone receptor 20.0%. Hormone receptor discordance was
not associated with patient survival. The proportion of the PR-ER+AR- subgroup,
which exhibited the worst prognosis, was higher in recurrent than primary tumor
specimens. Our study demonstrated that paired primary and recurrent HGSC
specimens exhibit differing hormone receptor profiles. Thus, to most effectively
identify patient-specific therapies, biomarker status re-assessment is required
for recurrent patients.
PMID- 28416764
TI - A recombinant fungal compound induces anti-proliferative and pro-apoptotic
effects on colon cancer cells.
AB - Finding intracellular pathways and molecules that can prevent the proliferation
of colon cancer cells can provide significant bases for developing treatments for
this disease. Ostreolysin (Oly) is a protein found in the mushroom Pleurotus
ostreatus, and we have produced a recombinant version of this protein (rOly).We
measured the viability of several colon cancer cells treated with rOly.
Xenografts and syngeneic colon cancer cells were injected into in vivo mouse
models, which were then treated with this recombinant protein.rOly treatment
induced a significant reduction in viability of human and mouse colon cancer
cells. In contrast, there was no reduction in the viability of normal epithelial
cells from the small intestine. In the search for cellular targets of rOly, we
showed that it enhances the anti-proliferative activity of drugs targeting
cellular tubulin. This was accompanied by a reduction in the weight and volume of
tumours in mice injected with rOly as compared to their respective control mice
in two in vivo models.Our results advance the functional understanding of rOly as
a potential anti-cancer treatment associated with pro-apoptotic activities
preferentially targeting colon cancer cells.
PMID- 28416765
TI - LoLoPicker: detecting low allelic-fraction variants from low-quality cancer
samples.
AB - INTRODUCTION: Although several programs are designed to identify variants with
low allelic-fraction, further improvement is needed, especially to push the
detection limit of low allelic-faction variants in low-quality, "noisy" tumor
samples. RESULTS: We developed LoLoPicker, an efficient tool dedicated to calling
somatic variants from next-generation sequencing (NGS) data of tumor sample
against the matched normal sample plus a user-defined control panel of additional
normal samples. The control panel allows accurately estimating background error
rate and therefore ensures high-accuracy mutation detection. CONCLUSIONS:
Compared to other methods, we showed a superior performance of LoLoPicker with
significantly improved specificity. The algorithm of LoLoPicker is particularly
useful for calling low allelic-fraction variants from low-quality cancer samples
such as formalin-fixed and paraffin-embedded (FFPE) samples.Implementation and
Availability: The main scripts are implemented in Python-2.7 and the package is
released at https://github.com/jcarrotzhang/LoLoPicker.
PMID- 28416766
TI - Notch3 overexpression enhances progression and chemoresistance of urothelial
carcinoma.
AB - Abnormal activation of Notch signaling is involved in the etiology of various
diseases, including cancer, but the association between Notch3 expression in
urothelial cancer and clinical outcome remains unclear, and the molecular
mechanisms underlying Notch3 signaling activation are not well defined. In this
study we examined 59 urothelial cancer patients and found that Notch3 was more
highly expressed in human urothelial cancer tissues than in non-tumorous bladder
tissue samples, with Notch3 overexpression being associated with poor clinical
outcome. Notch3 knockdown resulted in decreased proliferation of urothelial
cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition,
Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin.
Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC]
inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented
urothelial cancer cell proliferation, and induced cell cycle arrest. Taken
together, these data suggested that Notch 3 overexpression promotes growth and
chemoresistance in urothelial cancer.
PMID- 28416767
TI - The molecular heterogeneity of sporadic colorectal cancer with different tumor
sites in Chinese patients.
AB - PURPOSE: To assess the biological variability of clinical meaningful molecular
markers and their clinical correlations in Chinese patients with colorectal
cancer (CRC). MATERIALS AND METHODS: In this prospective observational study,
frequencies and clinico-pathological features of RAS and BRAFV600E mutations,
deficiency of DNA mismatch repair (dMMR) were evaluated in patients with
colorectal cancer staged I-IV. The molecular heterogeneity between right-sided
and left-sided colorectal cancers was studied in our series by classifying
patients with different mutations and dMMR status. RESULTS: Among 400 evaluable
patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected
in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly
higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5%
vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in
older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right
sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of
CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer.
CONCLUSIONS: By assessing the mutations and clinical correlations of RAS and BRAF
genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF
mutation was observed in Chinese patients compared to western patients. A
distinct molecular heterogeneity was found between patients with right-sided and
left-sided CRCs.
PMID- 28416768
TI - Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell
recruitment and CCR7+ tumor cell mobilization.
AB - Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is
expressed by cancer associated fibroblasts (CAFs). In malignant transformation,
PDPN is subjected to changes and its role is yet to be established. Here we show
that it is involved in modulating the activity of the CCL21/CCR7
chemokine/receptor axis in a hypoxia-dependent manner. In the present model,
breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor
for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The
impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3
cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor
environment. In addition to its known effect on migration, CCL21/CCR7 interaction
was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction
by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the
same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism
through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression
undergoes a reduction of adhesion, making it an anti-adhesion molecule in the
absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231
cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia
dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which
influence PDPN expression.
PMID- 28416769
TI - Nuclear organization of nucleotide excision repair is mediated by RING1B
dependent H2A-ubiquitylation.
AB - One of the major cellular DNA repair pathways is nucleotide excision repair
(NER). It is the primary pathway for repair of various DNA lesions caused by
exposure to ultraviolet (UV) light, such as cyclobutane pyrimidine dimers (CPDs)
and 6-4 photoproducts. Although lesion-containing DNA associates with the nuclear
matrix after UV irradiation it is still not understood how nuclear organization
affects NER. Analyzing unscheduled DNA synthesis (UDS) indicates that NER
preferentially occurs in specific nuclear areas, viz the nucleolus. Upon inducing
localized damage, we observe migration of damaged DNA towards the nucleolus.
Employing a LacR-based tethering system we demonstrate that H2A-ubiquitylation
via the UV-RING1B complex localizes chromatin close to the nucleolus. We further
show that the H2A-ubiquitin binding protein ZRF1 resides in the nucleolus, and
that it anchors ubiquitylated chromatin along with XPC. Our data thus provide
insight into the sub-nuclear organization of NER and reveal a novel role for
histone H2A-ubiquitylation.
PMID- 28416770
TI - NID1, a new regulator of EMT required for metastasis and chemoresistance of
ovarian cancer cells.
AB - Nidogen-1 (NID1) has been identified as a novel candidate diagnostic biomarker of
ovarian cancer in our previous study. Nevertheless, the role of NID1 in the
pathogenesis of ovarian cancer is unclear. In the present study, we demonstrated
that NID1 was a mesenchymal associated gene and its high expression was
significantly correlated with shorter overall survival of ovarian cancer
patients. The ectopic expression of NID1 in OVCAR-3 cells revealed a epithelial
mesenchymal transition (EMT) phenotype accompanied by enhancement of motility,
invasiveness and cisplatin resistance, whereas the knockdown of NID1 was
sufficient to convert HEY cells into epithelial phenotype with decreased
capability of motility, invasiveness and cisplatin resistance. Mechanistic
studies disclosed that NID1 activated ERK/MAPK signaling pathway to promote EMT.
Collectively, our findings have uncovered the molecular mechanisms of NID1 in
promoting ovarian cancer metastasis and chemoresistance, and provide a rationale
for the therapeutic potential of NID1 suppression in ovarian cancer.
PMID- 28416771
TI - XPG gene polymorphisms and cancer susceptibility: evidence from 47 studies.
AB - Xeroderma pigmentosum group G (XPG) is a single-strand-specific DNA endonuclease
that functions in the nucleotide excision repair pathway. Genetic variations in
XPG gene can alter the DNA repair capacity of this enzyme. We evaluated the
associations between six single nucleotide polymorphisms (SNPs) in XPG (rs1047768
T>C, rs2296147 T>C, rs2227869 G>C, rs2094258 C>T, rs751402 C>T, and rs873601 G>A)
and cancer risk. Forty-seven studies were identified in searches of the PubMed,
Scopus, Web of Science, China National Knowledge Infrastructure, and WanFang
databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were
calculated using a fixed or random effects model. We found that rs873601 G>A was
associated with an increased overall cancer risk (AA vs. GG: OR = 1.14, 95% CI =
1.06-1.24; GA/AA vs. GG: OR = 1.08, 95% CI = 1.02-1.15; A vs. G: OR = 1.06, 95%
CI = 1.02-1.10). In a stratified analysis, rs1047768 T>C was associated with an
increased risk of lung cancer, rs2227869 G>C was associated with a decreased risk
of cancer in population-based studies, and rs751402 C>T and rs873601 G>A were
associated with the risk of gastric cancer. Our data indicate that rs873601 G>A
is associated with cancer susceptibility.
PMID- 28416772
TI - DNA methylation of METTL7A gene body regulates its transcriptional level in
thyroid cancer.
AB - DNA methylation is the best-studied epigenetic mechanism for regulating gene
transcription and maintaining genome stability. Current research progress of
transcriptional regulation by DNA methylation mostly focuses on promoter region
where hypomethylated CpG islands are present transcriptional activity, as
hypermethylated CpG islands generally result in gene repression. Recently, the
DNA methylation patterns across the gene body (intragenic methylation) have
increasingly attracted attention towards their role in transcriptional regulation
and efficiency, due to the improvement of numerous genome-wide DNA methylation
profiling studies. However, the function and mechanism of gene body methylation
is still unclear. In this study, we revealed that the methylation level of
METTL7A, a seldom studied gene, was downregulated in thyroid cancer compared to
normal thyroid cells in vivo and in vitro. Moreover, we determined the
methylation level of one CpG site at the exon of the METTL7A gene body impacted
the transcriptional activity. Through generating a mutation of this CpG site (CG
to CC) of METTL7A exogenous vector artificially in vitro, we observed higher RNA
polymerase II recruitment and a declined enrichment of methyl-CpG binding protein
2 in gene body of METTL7A, in papillary thryoid cancer cells (BCPAP) compared to
normal thryoid cells. Finally, we revealed that EZH2, a subunit of polycomb
repressor complex 2, dominant in thyroid cancer, might be responsible for
regulating gene body methylation of METTL7A. Our study depicted the DNA
methylation patterns and the transcriptional regulatory mechanism of the gene
body in thyroid cancer. Furthermore, this study provides new insight into
potential future avenues, for therapies targeting cancer.
PMID- 28416773
TI - Changes in T-cell subpopulations and cytokine network during early period of
ibrutinib therapy in chronic lymphocytic leukemia patients: the significant
decrease in T regulatory cells number.
AB - B cell receptor (BCR) stimulation signal plays an important role in the
pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors
directed toward the BCR pathway are now the promising anti-leukemic drugs.
Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical
activity in CLL. It is reported that ibrutinib, additionally to directly
targeting leukemic cells, also inhibits the interactions of these cells with T
cells, macrophages and accessory cells. Assessment of these mechanisms is
important because of their non -direct anti-leukemic effects and to identify
possible side effects connected with long-term drug administration.The aim of
this study was to assess the in vivo effects of ibrutinib on T-cell
subpopulations and cytokine network in CLL. The analysis was performed on a group
of 19 patients during first month of ibrutinib therapy. The standard multicolor
flow cytometry and cytometric bead array methods were used for assessment of T
cell subsets and cytokines/chemokines, respectively.The data obtained indicates
that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine
network in CLL patients. Particularly, a significant reduction of T regulatory
cells in peripheral blood was observed. By targeting these populations of T cells
Ibrutinib can stimulate rejection of tumor cells by the immune system.
PMID- 28416774
TI - MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo
resistance via ZNRF2.
AB - Osteosarcoma (OS) is a prevalent cancer worldwide. MicroRNAs (miRNAs) play
critical roles in the growth, invasion and carcinogenesis of OS, whereas the
underlying mechanisms remain ill-defined. Here, we addressed these questions. We
detected significantly higher levels of ZNRF2, a ubiquitin ligase of the RING
superfamily, and significantly lower levels of miR-100 in the OS specimens,
compared to the paired normal bone tissues. The levels of ZNRF2 and miR-100
inversely correlated in the OS specimens. In addition, low miR-100 levels are
associated with poor prognosis of the OS patients. Either ZNRF2 overexpression or
miR-100 depletion increased in vitro OS cell growth and improved cell survival at
the presence of Doxorubicin. Mechanistically, with the help of bioinformatics
analysis and luciferase-reporter assay, we found that miR-100 might bind to the
3'-UTR of ZNRF2 mRNA to prevent its protein translation. Thus, our data suggest
that re-expression of miR-100 may inhibit OS cell growth and decrease OS cell
chemo-resistance.
PMID- 28416775
TI - Volatile organic compounds in gastrointestinal stromal tumour tissue originating
from patient-derived xenografts.
AB - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal
neoplasms of the gastrointestinal tract and localize mainly in the stomach or
small intestine. The metabolomic signatures of GISTs driven by different KIT gene
mutations remain undiscovered and unexplored. The main aim of this pilot study
was to determine and compare metabolomic profiles in GIST xenograft models with
different genetic backgrounds. Metabolomic profiling using gas chromatography
coupled with mass spectrometry followed by univariate and multivariate
statistical analyses was applied to select metabolites that differentiated the
GIST models studied. The significant differences observed in the metabolites were
mainly derived from glycolysis, the citric acid cycle and glutamine and lipid
metabolism. The obtained results may suggest variable metabolomic signatures of
tumours, possibly related to the different underlying, specific KIT gene
mutations and with potential implications for the biological behaviour and
natural course of this rare disease. This study constitutes a proof of concept in
GISTs and reveals the potential of the metabolomic approach in orphan
malignancies.
PMID- 28416777
TI - Intervention Therapy for Portal Vein Stenosis/Occlusion After Pediatric Liver
Transplantation.
AB - BACKGROUND The aim of this study was to investigate the outcomes and stent
implantation timing of portal vein stenosis intervention after pediatric liver
transplantation (pLT). MATERIAL AND METHODS The clinical data of 30 children with
post-liver transplantation portal vein stenosis/occlusion (PVS/O) between Jan
2008 and Jun 2015 were retrospectively analyzed. The successfully re-opened cases
used balloon angioplasty or stent implantation. SPSS13.0 software was used for
statistical analysis and paired t test of the pressure gradient at both ends of
the stenosis, diameter and flow rate within the stenosis, platelet count, and
albumin in the PVS children before and after balloon angioplasty, with p<0.05
considered as statistically significant. Among the 30 patients, 6 received a
stent implant in their first treatment, 22 received balloon angioplasty in their
first treatment, and in 2 the re-opening could not be achieved. RESULTS The
diameter of the stenotic segment, portal vein velocity, pressure gradient at both
ends of the stenosis, and platelet count in these children with portal vein
stenosis/occlusion (PVS/O) showed statistically significant differences when
comparing values before and after intervention (p<0.05), but albumin showed no
statistically significant difference (p>0.05). CONCLUSIONS Intervention therapy
for portal vein stenosis after pediatric liver transplantation (pLT-PVS) is a
safe and effective treatment, and patients with portal vein torsion, intimal
tearing, or long portal vein segment occlusion should undergo stent implantation.
PMID- 28416776
TI - Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets
in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and
Bioinformatics.
AB - BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion,
and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not
fully understood. Therefore, a comprehensive analysis of the target genes,
pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The
miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA)
were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected
MCF-7 cells and scramble control cells was downloaded from Gene Expression
Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The
potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO)
and pathway and network analyses were constructed for the DEGs and predicted
genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might
represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic
(HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER),
progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2),
and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis
(M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and
the 7924 potential target genes from the prediction databases. These genes were
related to transcription, metabolism, biosynthesis, and proliferation. The
results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt,
and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be
prospective biomarkers for the prognosis and diagnosis of BC, respectively, and
are associated with diverse clinical parameters. The target genes of miR-101-3p
regulate the development and progression of BC. These results provide insight
into the pathogenic mechanism and potential therapies for BC.
PMID- 28416778
TI - Steroid Pulse Therapy for De Novo Minimal Change Disease During Pregnancy.
AB - BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of
all pregnancies, and de novo minimal change disease during pregnancy is
especially rare. Nephrotic syndrome and, especially, minimal change disease are
highly responsive to steroids, and preterm labor may be avoidable if the maternal
condition is improved with steroid therapy. Therefore, prompt diagnosis and
proper management are critical to maternal and fetal outcome when severe
proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese
woman presented with systemic edema, oliguria, and severe proteinuria and
hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The
patient had high urinary protein selectivity. Her illness was diagnosed as de
novo nephrotic syndrome with high steroid responsiveness rather than pre
eclampsia. She began steroid pulse therapy the day after admission. Complete
remission was confirmed after 3 weeks. The patient did not relapse during
pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal
biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS
In pregnant women with de novo minimal change disease, serious maternal and/or
fetal complications may occur if severe proteinuria and hypoalbuminemia are
unabated for an extended time. Evaluation of urinary protein selectivity is
noninvasive and useful for prediction of steroid responsiveness. Results of
urinary protein selectivity can be obtained earlier than results of renal biopsy.
Renal biopsy during pregnancy is not always necessary for initiation of steroid
therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement
of remission and prevent serious perinatal complications.
PMID- 28416779
TI - Neuronal network models of epileptogenesis.
AB - Epilepsy is a chronic neurological condition, following some trigger,
transforming a normal brain to one that produces recurrent unprovoked seizures.
In the search for the mechanisms that best explain the epileptogenic process,
there is a growing body of evidence suggesting that the epilepsies are network
level disorders. In this review, we briefly describe the concept of neuronal
networks and highlight 2 methods used to analyse such networks. The first method,
graph theory, is used to describe general characteristics of a network to
facilitate comparison between normal and abnormal networks. The second, dynamic
causal modelling, is useful in the analysis of the pathways of seizure spread. We
concluded that the end results of the epileptogenic process are best understood
as abnormalities of neuronal circuitry and not simply as molecular or cellular
abnormalities. The network approach promises to generate new understanding and
more targeted treatment of epilepsy.
PMID- 28416780
TI - New onset epilepsy in the elderly: clinical, radiological and
electroencephalographic features and treatment responses.
AB - OBJECTIVE: To evaluate new onset epilepsy characteristics, etiology, radiological
and electroencephalographic features and to document treatment response in the
elderly. METHODS: This was a retrospective study carried out in King Fahd Medical
City, Riyadh, Kingdom of Saudi Arabia, from 2010 to 2013. Medical records were
searched to recruit patients. Hundred and nineteen patients were enrolled who
fulfill the inclusion criteria. Clinical data with respect to seizure semiology,
etiology, electroencephalographic findings, radiological findings, co
morbidities, and anti-epileptic drug (AED) therapy were assessed. RESULTS:
Cerebrovascular disease was the most common etiology, followed by occult
cerebrovascular disease (oCVD). Focal onset seizures were the most common
clinical presentation in this group of cohort. Electroencephalogram (EEG) showed
generalized slowing in majority of patients (45.5%), with 21.8% interictal
epileptiform activity. Patients required lower doses of AEDs to control seizures,
gain better seizure control. Common co-morbidities were hypertension and diabetes
mellitus. CONCLUSION: Patients presenting with LOE, should have search for any
other cerebrovascular risk factors. Further research is needed to determine the
prevalence of oCVD in LOE, and to investigate whether addressing cerebrovascular
risk factors in this cohort of patients can reduce the incidence of stroke.
PMID- 28416781
TI - Incidence, risk factors and outcomes of seizures occurring after craniotomy for
primary brain tumor resection.
AB - OBJECTIVE: To determine the incidence, risk factors and outcomes of early post
craniotomy seizures. METHODS: This was a retrospective cohort study of all
patients who underwent craniotomy for primary brain tumor resection (2002-2011)
and admitted postoperatively to the intensive care unit. The patients were
divided into 2 groups depending on the occurrence of seizures within 7 days.
RESULTS: One-hundred-ninety-three patients were studied: 35.8% had preoperative
seizure history and 16.6% were on prophylactic antiepileptic drugs (AEDs). Twenty
seven (14%) patients had post-craniotomy seizures. The tumors were mostly
meningiomas (63% for the post-craniotomy seizures group versus 58.1% for the
other group; p=0.63) and supratentorial (92.6% for the post-craniotomy seizures
versus 78.4% for the other group, p=0.09) with tumor diameter=3.7+/-1.5 versus
4.2+/-1.6 cm, (p=0.07). One (3.1%) of the 32 patients on prophylactic AEDs had
post-craniotomy seizures compared with 12% of the 92 patients not receiving AEDs
preoperatively (p=0.18). On multivariate analysis, predictors of post-craniotomy
seizures were preoperative seizures (odds ratio, 2.62; 95% confidence interval,
1.12-6.15) and smaller tumor size <4 cm (odds ratio, 2.50; 95% confidence
interval, 1.02-6.25). Post-craniotomy seizures were not associated with increased
morbidity or mortality. CONCLUSION: Early seizures were common after craniotomy
for primary brain tumor resection, but were not associated with worse outcomes.
Preoperative seizures and smaller tumor size were independent risk factors.
PMID- 28416782
TI - Assessment of atherosclerotic risk among patients with epilepsy on valproic acid,
lamotrigine, and carbamazepine treatment.
AB - OBJECTIVE: To compare the long-term effects of carbamazepine (CBZ), valproic acid
(VPA), and lamotrigine (LTG) as monotherapy on the markers of vascular risk.
METHODS: The present cross-sectional study was carried out at the Department of
Neurology, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from
2012 to 2013. We selected 120 adult patients with epilepsy and 40 control
subjects. The patients with epilepsy were divided into 3 groups according to the
use of antiepileptic drugs (AEDs) (CBZ, n = 40; VPA, n = 40; and LTG, n = 40).
All participants' total cholesterol (TC), triglycerides (TG), low-density
lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL
c), high-density lipoprotein cholesterol (HDL-c), ratio of TC/HDL-c, ratio of LDL
c/HDL-c, body mass index (BMI), and blood pressure was determined. RESULTS: In
patients with epilepsy, CBZ and VPA treatment caused a noteworthy increase in the
concentrations of TG, TC, and LDL-c compared with LTG treatment and the control
group (p<0.001). The HDL-c significantly decreased in CBZ, VPA, and LTG-treated
patients as compared with controls (p<0.001). The ratio of LDL-c/HDL-c and TC/HDL
c significantly increased in VPA- and CBZ-treated groups compared with the LTG
treated, and control group, while the ratio was also considerably elevated in
patients treated with CBZ as compared with the patients treated with VPA. The
weight and BMI of the patients treated with AEDs were higher (p<0.01).
CONCLUSION: Patients with epilepsy on CBZ or VPA have changed vascular risk
markers that may lead to atherosclerosis, while LTG-treated patients have less
alteration in lipid profile.
PMID- 28416783
TI - Predictive and prognostic role of mean platelet volume in patients with first
ever acute ischemic stroke.
AB - OBJECTIVE: To investigate any possible effects of mean platelet volume (MPV) on
short-term stroke prognosis and functional outcome in patients with first-ever
acute ischemic stroke (FEAIS). METHODS: This retrospective cross-sectional study
included 798 FEAIS patients admitted to the emergency department of a tertiary
care hospital in Adiyaman, Turkey between January 2013 and June 2015. The data
were evaluated according to whether alive or dead, MPV levels, modified Rankin
scale (MRS) scores, National Institutes of Health Stroke Scale (NIHSS) scores.
The patients were divided into 3 groups based on MPV level as 4.4-7.4 fL, 7.5
10.4 fL, higher than 10.4 fL. RESULTS: A total of 250 patients with FEAIS were
included in the study. In both those who survived and those who died, the area
under the curve related to hospitalization days, time interval of venipuncture
(TIV), and MPV measurements was not statistically significant (p>0.05). The 3 MPV
groups showed no significant differences in terms of MRS score, median NIHSS
score, hospitalization, and TIV. In subgroups based on MRS scores, there were no
statistically significant differences according to median latency (p=0.087),
median hospitalization (p=0.394), TIV (p=0.201), and MPV levels (p=0.847).
Furthermore, there were no differences in MPV levels between the MRS based groups
(p=0.527). CONCLUSION: The results showed that MPV was not a significantly
associated and reliable marker for the prediction of prognosis or functional
outcome of FEAIS attack.
PMID- 28416784
TI - Longitudinal extensive transverse myelitis (LETM) in children: A twenty-year
study from Oman.
AB - OBJECTIVE: The data on children with diagnosis of idiopathic transverse myelitis
(ITM) was searched to find the pattern of myelitis in Oman. METHODS: A
retrospective study was carried out from January1995 to December 2014. Electronic
medical records and patient medical files were seen to get the complete data of
the children with ITM. This work was carried out at Sultan Qaboos University
hospital, Muscat, Oman. The ethical committee of the hospital had approved the
study. The diagnosis was based on the established criteria. Other causes of
myelopathy were excluded. RESULTS: 19 children with idiopathic transverse
myelitis were found. There were 18 out of 19 (94.6%) children with longitudinal
extensive transverse myelitis (LETM). CONCLUSION: Longitudinal transverse
extensive myelitis is the most common form of ITM in Oman.
PMID- 28416785
TI - A novel mutation in the glycine decarboxylase gene in patient with non-ketotic
hyperglycinemia.
AB - Non-ketotic hyperglycinemia (NKH) is a rare inborn error of metabolism and is
caused by a glycine cleavage system deficiency. Eighty-five percent of patients
present with the neonatal type of NKH, the infants initially develop lethargy,
seizures, and episodes of apnea, and most often death. Between 60-90% of cases
are caused by mutations in the glycine decarboxylase (GLDC). We believed that
more mutation reports especially for rare disease as NKH help to evaluate the
genotype-phenotype relationship in patients with GLDC. In this study, we describe
a case of a neonate admitted to intensive care unit with hypotonia, respiratory
failure, lethargy, poor feeding. Due to the history of 2 non-ketotic
hyperglycinemia diagnosed male siblings, molecular prenatal diagnosis in patient
was performed and a novel c.2963G>A (Arg998Gln) homozygous mutation within the
GLDC gene has been detected. We aimed to contribute to mutation knowledge pool of
GLDC gene with a novel mutation.
PMID- 28416786
TI - Basilar artery vasospasm after pretuncal non-aneurysmal subarachnoid hemorrhage
responding to milrinone.
AB - Pretruncal (perimesencephalic) non-aneurysmal subarachnoid hemorrhage (PNSAH) is
uniformly associated with an excellent outcome. Although cerebral vasospasm
remains a common complication of SAH and constitutes an important predictor of
outcome, in the setting of PNSAH, it is extremely rare. Preturnal non-aneurysmal
subarac refers to a subset of SAH patients with a characteristic pattern of
localized blood on CT of the head, normal cerebral angiography, and benign course
when compared to the aneurysmal SAH population. The presence of radiological or
even clinical vasospasm does not exclude the diagnosis of PNSAH. To our
knowledge, this is the first case of symptomatic cerebral vasospasm due to PNSAH
that responded to milrinone.
PMID- 28416787
TI - A family with hereditary cerebellar ataxia finally confirmed as Gerstmann
Straussler-Scheinker syndrome with P102L mutation in PRNP gene.
AB - Gerstmann-Straussler-Scheinker syndrome (GSS) is an exceedingly rare prion
disease. There are only 3 case reports of GSS in China. Here we report the first
GSS family in southern China. A 47-year-old female complained of unsteady gait
and dysarthria. Seven other individuals presented similar symptoms in 3
generations of her family, and all died 4-6 years after onset. To detect
causative mutations, we employed a gene analysis panel of hereditary diseases.
This revealed a P102L mutation in the prion protein gene (PRNP) gene, which is
commonly found in GSS featuring cerebellar ataxia. However, GSS is an uncommon
cause of hereditary cerebellar ataxia that might be overlooked because many
neurologists are unfamiliar with it. To avoid misdiagnosis in the patients with
hereditary cerebellar ataxia, GSS should be taken into account if other causes
are absent, especially in patients that have accompanying psychiatric symptoms
and a short survival time.
PMID- 28416788
TI - Characteristics of Arabic Websites with information on autism.
AB - OBJECTIVE: To explore the characteristics of Arabic websites with information on
autism spectrum disorder (ASD). METHODS: The word autism in Arabic was entered
into 2 popular search engines in September 2013 to locate the top 80 websites
featuring the term. Websites were sorted using 10 characteristics, previously
used to evaluate the characteristics of English websites with information on ASD.
RESULTS: Most websites were registered using a .com top-level domain (69%), were
an individual's site, forum, or blog (44%), and were updated after September 2012
(60%); they contained images or texts that seemed to persuade viewers to purchase
products (43%); they provided information with the name of author(s) (64%); they
described the basic characteristics of ASD; and they promoted various types of
treatments, most of which lack empirical support (63%). However, few websites
contained information with references to peer review resources (3%) or a warning
statement that such information should not replace the opinion of a qualified
professional (8%). CONCLUSION: Internet users may not find Arabic websites to be
reliable sources to obtain information on ASD. Given the increased use of the
internet, creation of websites that contain trusted information on ASD could
potentially aid parents in accessing available services, help them learn about
empirically validated interventions, and enable them to advocate for their
children's rights.
PMID- 28416789
TI - Pantothenate kinase-associated neurodegeneration.
PMID- 28416790
TI - A meta-analysis of cerebrospinal fluid visinin-like protein-1 in alzheimers
disease patients relative to healthy controls and mild cognitive impairment
patients.
AB - OBJECTIVE: To compare cerebrospinal fluid visinin-like protein-1 (CSF VLP-1) in
alzheimer's disease (AD) with that in healthy controls and mild cognitive
impairment (MCI) patients and find out possible sources of heterogeneity.
METHODS: "Visinin-like protein-1" and "alzheimer's disease" were employed to
search "PubMed", "Springer" and "Medline" databases until July 2016 and standard
mean difference (Std.MD) was calculated. Besides, subgroup analysis and meta
regression were performed to explore the possible heterogeneity sources. RESULTS:
Seven studies involved 1151 participants were pooled. The CSF VLP-1 in AD
patients was higher than that in healthy controls and MCI patients (pooled
Std.MD=0.81, 95% CI: [0.47, 1.16], p<0.00001). As shown by subgroup analysis,
population variations were one of heterogeneity sources. Meta-regression revealed
that Hedges's g of CSF VLP-1 was correlated with Std.MD of t-tau (r=0.560,
p=0.006) and amyloid beta42 (r=-0.386, p=0.013). CONCLUSION: The CSF VLP-1 in AD
patients is higher than that in healthy controls and MCI patients. The changes of
VLP-1 in AD patients relative to healthy controls and MCI patients is less
pronounced than that of core biomarkers, such as amyloid beta42, t-tau and p-tau.
Population variations, increasing t-tau and decreasing amyloid beta42 in AD
patients relative to healthy controls and MCI patients were the main sources of
heterogeneity.
PMID- 28416791
TI - Management of convulsive status epilepticus in children: an adapted clinical
practice guideline for pediatricians in Saudi Arabia.
PMID- 28416792
TI - Corrigendum: The OncoPPi network of cancer-focused protein-protein interactions
to inform biological insights and therapeutic strategies.
PMID- 28416793
TI - Seismic anisotropy of the D" layer induced by (001) deformation of post
perovskite.
AB - Crystallographic preferred orientation (CPO) of post-perovskite (Mg,Fe)SiO3 (pPv)
has been believed to be one potential source of the seismic anisotropic layer at
the bottom of the lower mantle (D" layer). However, the natural CPO of pPv
remains ambiguous in the D" layer. Here we have carried out the deformation
experiments of pPv-(Mg0.75,Fe0.25)SiO3 using synchrotron radial X-ray diffraction
in a membrane-driven laser-heated diamond anvil cell from 135 GPa and 2,500 K to
154 GPa and 3,000 K. Our results show that the intrinsic texture of pPv
(Mg0.75,Fe0.25)SiO3 should be (001) at realistic P-T conditions of the D" layer,
which can produce a shear wave splitting anisotropy of ~3.7% with VSH>VSV.
Considering the combined effect of both pPv and ferropericlase, we suggest that
50% or less of deformation is sufficient to explain the origin of the shear wave
anisotropy observed seismically in the D" layer beneath the circum-Pacific rim.
PMID- 28416794
TI - Stability of the frequent COPD exacerbator in the general population: A Danish
nationwide register-based study.
AB - : Exacerbation frequency is central in treatment strategies for chronic
obstructive pulmonary disease. However, whether chronic obstructive pulmonary
disease patients from the general population with frequent exacerbations continue
to have frequent exacerbations over an extended period of time is currently
unknown. In this study, we aimed to investigate the stability of the frequent
exacerbator in a population-based setting. To this end, we conducted a nationwide
register-based descriptive study with a 10-year follow-up period of chronic
obstructive pulmonary disease patients with at least one medically treated
exacerbation in 2003. Each subsequent year, we divided the population into
frequent, infrequent and non-exacerbators and quantified the flow between
categories. Further, we estimated the percentage of frequent exacerbators at
baseline who stayed in this category each year during a 5-year follow-up. We
identified 19,752 patients with chronic obstructive pulmonary disease and an
exacerbation in 2003. Thirty percent were frequent exacerbators. Overall, the
majority of exacerbators in 2003 were non-exacerbators in the following years
(60% in 2004 increasing to 68% in 2012). Approximately half of frequent
exacerbators in one year experienced a decrease in exacerbation frequency and had
either zero or one exacerbation in the subsequent year. This pattern was stable
throughout follow-up. During a 5-year follow-up period, a substantial proportion
(42%) of frequent exacerbators in 2003 had no additional years as frequent
exacerbators, while the minority (6%) remained in this category each year. In
conclusion, the rate of exacerbations shows considerable variation over time
among chronic obstructive pulmonary disease patients in the general population.
This might hold implications for chronic obstructive pulmonary disease treatment
guidelines and their practical application. CHRONIC OBSTRUCTIVE LUNG DISEASE:
VARIATIONS IN DISEASE PROGRESSION: Patients with chronic obstructive pulmonary
disease (COPD) who suffer from frequent exacerbations do not necessarily persist
with such severity over time. Exacerbations in COPD are defined by worsening
respiratory symptoms that result in changes to treatment, hospitalization and, at
worst, death. However, clarity is needed on whether frequent exacerbations is a
stable feature of some patients' disease. Mette Reilev at the University of
Southern Denmark and co-workers followed, over 10 years, 19,752 COPD patients
living in Denmark who suffered at least one exacerbation in 2003. By 2004, 60% of
patients were classed as infrequent or non-exacerbators, rising to 68% by 2012.
Very few patients remained "frequent exacerbators", suggesting the rate of
exacerbations changes considerably over time. This could hold implications for
COPD treatment and challenge assumptions made about disease progression.
PMID- 28416795
TI - Neutrophil stunning by metoprolol reduces infarct size.
AB - The beta1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size
in acute myocardial infarction (AMI) patients. The prevailing view has been that
metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol
reduces reperfusion injury by targeting the haematopoietic compartment.
Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol
acts during early phases of neutrophil recruitment by impairing structural and
functional rearrangements needed for productive engagement of circulating
platelets, resulting in erratic intravascular dynamics and blunted inflammation.
Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade
of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully
abrogated metoprolol's infarct-limiting effects. The association between
neutrophil count and microvascular obstruction is abolished in metoprolol-treated
AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI
patients by targeting neutrophils. Identification of the relevant role of ADRB1
in haematopoietic cells during acute injury and the protective role upon its
modulation offers potential for developing new therapeutic strategies.
PMID- 28416796
TI - Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell
surface.
AB - Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the
extracellular matrix. LOX overexpression is associated with poor cancer outcomes.
Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to
drive tumour progression. We show that LOX regulates EGFR by suppressing TGFbeta1
signalling through the secreted protease HTRA1. This increases the expression of
Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the
cell surface to facilitate its activation by EGF. We describe a pharmacological
inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and
delays the growth of primary and metastatic tumour cells in vivo. Thus, we show
that LOX regulates EGFR cell surface retention to drive tumour progression, and
we validate the therapeutic potential of inhibiting this pathway with the small
molecule inhibitor CCT365623.
PMID- 28416798
TI - Neurotransmission: Widening exocytosis.
PMID- 28416797
TI - Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma.
AB - The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high
response rates in B-cell lymphomas; however, a growing number of ibrutinib
treated patients relapse with resistance and fulminant progression. Using
chemical proteomics and an organotypic cell-based drug screening assay, we
determine the functional role of the tumour microenvironment (TME) in ibrutinib
activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop
ibrutinib resistance through evolutionary processes driven by dynamic feedback
between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing
the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin
beta1 signalling. Combinatorial disruption of B-cell receptor signalling and PI3K
AKT-mTOR axis leads to release of MCL cells from TME, reversal of drug resistance
and enhanced anti-MCL activity in MCL patient samples and patient-derived
xenograft models. This study unifies TME-mediated de novo and acquired drug
resistance mechanisms and provides a novel combination therapeutic strategy
against MCL and other B-cell malignancies.
PMID- 28416803
TI - Optical-helicity-driven magnetization dynamics in metallic ferromagnets.
AB - Recent observations of switching of magnetic domains in ferromagnetic metals by
circularly polarized light, so-called all-optical helicity dependent switching,
has renewed interest in the physics that governs the interactions between the
angular momentum of photons and the magnetic order parameter of materials. Here
we use time-resolved-vectorial measurements of magnetization dynamics of thin
layers of Fe, Ni and Co driven by picosecond duration pulses of circularly
polarized light. We decompose the torques that drive the magnetization into field
like and spin-transfer components that we attribute to the inverse Faraday effect
and optical spin-transfer torque, respectively. The inverse Faraday effect is
approximately the same in Fe, Ni and Co, but the optical spin-transfer torque is
strongly enhanced by adding a Pt capping layer. Our work provides quantitative
data for testing theories of light-material interactions in metallic ferromagnets
and multilayers.
PMID- 28416802
TI - RNA editing-dependent epitranscriptome diversity in cancer stem cells.
AB - Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of
their stem cell-like capacity to self-renew, survive and become dormant in
protective microenvironments. CSCs evolve during tumour progression in a manner
that conforms to Charles Darwin's principle of natural selection. Although
somatic DNA mutations and epigenetic alterations promote evolution, post
transcriptional RNA modifications together with RNA binding protein activity (the
'epitranscriptome') might also contribute to clonal evolution through dynamic
determination of RNA function and gene expression diversity in response to
environmental stimuli. Deregulation of these epitranscriptomic events contributes
to CSC generation and maintenance, which governs cancer progression and drug
resistance. In this Review, we discuss the role of malignant RNA processing in
CSC generation and maintenance, including mechanisms of RNA methylation, RNA
editing and RNA splicing, and the functional consequences of their aberrant
regulation in human malignancies. Finally, we highlight the potential of these
events as novel CSC biomarkers as well as therapeutic targets.
PMID- 28416804
TI - Cumulative culture can emerge from collective intelligence in animal groups.
AB - Studies of collective intelligence in animal groups typically overlook potential
improvement through learning. Although knowledge accumulation is recognized as a
major advantage of group living within the framework of Cumulative Cultural
Evolution (CCE), the interplay between CCE and collective intelligence has
remained unexplored. Here, we use homing pigeons to investigate whether the
repeated removal and replacement of individuals in experimental groups (a key
method in testing for CCE) alters the groups' solution efficiency over successive
generations. Homing performance improves continuously over generations, and later
generation groups eventually outperform both solo individuals and fixed
membership groups. Homing routes are more similar in consecutive generations
within the same chains than between chains, indicating cross-generational
knowledge transfer. Our findings thus show that collective intelligence in animal
groups can accumulate progressive modifications over time. Furthermore, our
results satisfy the main criteria for CCE and suggest potential mechanisms for
CCE that do not rely on complex cognition.
PMID- 28416806
TI - Elevated CYP2C19 expression is associated with depressive symptoms and
hippocampal homeostasis impairment.
AB - This corrects the article DOI: 10.1038/mp.2016.204.
PMID- 28416805
TI - A new inhibitor of the beta-arrestin/AP2 endocytic complex reveals interplay
between GPCR internalization and signalling.
AB - In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis,
beta-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical
signalling cascades. Distinguishing the respective contributions of beta-arrestin
recruitment to the receptor and beta-arrestin-promoted endocytosis in propagating
receptor signalling has been limited by the lack of selective analytical tools.
Here, using a combination of virtual screening and cell-based assays, we have
identified a small molecule that selectively inhibits the interaction between
beta-arrestin and the beta2-adaptin subunit of the clathrin adaptor protein AP2
without interfering with the formation of receptor/beta-arrestin complexes. This
selective beta-arrestin/beta2-adaptin inhibitor (Barbadin) blocks agonist
promoted endocytosis of the prototypical beta2-adrenergic (beta2AR), V2
vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect
beta-arrestin-independent (transferrin) or AP2-independent (endothelin-A)
receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated
ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and beta2AR,
supporting the concept of beta-arrestin/AP2-dependent signalling for both G
protein-dependent and -independent pathways.
PMID- 28416807
TI - A simplified protocol for differentiation of electrophysiologically mature
neuronal networks from human induced pluripotent stem cells.
AB - Progress in elucidating the molecular and cellular pathophysiology of
neuropsychiatric disorders has been hindered by the limited availability of
living human brain tissue. The emergence of induced pluripotent stem cells
(iPSCs) has offered a unique alternative strategy using patient-derived
functional neuronal networks. However, methods for reliably generating iPSC
derived neurons with mature electrophysiological characteristics have been
difficult to develop. Here, we report a simplified differentiation protocol that
yields electrophysiologically mature iPSC-derived cortical lineage neuronal
networks without the need for astrocyte co-culture or specialized media. This
protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise
from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of
114 neurons derived from three independent iPSC lines confirmed their
electrophysiological maturity, including resting membrane potential (-58.2+/-1.0
mV), capacitance (49.1+/-2.9 pF), action potential (AP) threshold (-50.9+/-0.5
mV) and AP amplitude (66.5+/-1.3 mV). Nearly 100% of neurons were capable of
firing APs, of which 79% had sustained trains of mature APs with minimal
accommodation (peak AP frequency: 11.9+/-0.5 Hz) and 74% exhibited spontaneous
synaptic activity (amplitude, 16.03+/-0.82 pA; frequency, 1.09+/-0.17 Hz). We
expect this protocol to be of broad applicability for implementing iPSC-based
neuronal network models of neuropsychiatric disorders.
PMID- 28416808
TI - Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in
mouse.
AB - Synapse development and neuronal activity represent fundamental processes for the
establishment of cognitive function. Structural organization as well as
signalling pathways from receptor stimulation to gene expression regulation are
mediated by synaptic activity and misregulated in neurodevelopmental disorders
such as autism spectrum disorder (ASD) and intellectual disability (ID).
Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been
described in male patients with X-linked ID and/or ASD. The structure of PTCHD1
protein is similar to the Patched (PTCH1) receptor; however, the cellular
mechanisms and pathways associated with PTCHD1 in the developing brain are poorly
determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that
binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1
is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted
of PTCH1, suggesting that both proteins are involved in distinct cellular
signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y)
induces global changes in synaptic gene expression, affects the expression of the
immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory
synaptic structure and neuronal excitatory activity in the hippocampus, leading
to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results
support that PTCHD1 deficiency induces a neurodevelopmental disorder causing
excitatory synaptic dysfunction.
PMID- 28416809
TI - Perisomatic changes in h-channels regulate depressive behaviors following chronic
unpredictable stress.
AB - Chronic stress can be a precipitating factor in the onset of depression.
Lentiviral-mediated knockdown of HCN1 protein expression and reduction of
functional Ih produce antidepressant behavior. However, whether h-channels are
altered in an animal model of depression is not known. We found that perisomatic
HCN1 protein expression and Ih-sensitive physiological measurements were
significantly increased in dorsal but not in ventral CA1 region/neurons following
chronic unpredictable stress (CUS), a widely accepted model for major depressive
disorder. Cell-attached patch clamp recordings confirmed that perisomatic Ih was
increased in dorsal CA1 neurons following CUS. Furthermore, when dorsal CA1 Ih
was reduced by shRNA-HCN1, the CUS-induced behavioral deficits were prevented.
Finally, rats infused in the dorsal CA1 region with thapsigargin, an irreversible
inhibitor of the SERCA pump, exhibited anxiogenic-like behaviors and increased
Ih, similar to that observed following CUS. Our results suggest that CUS, but not
acute stress, leads to an increase in perisomatic Ih in dorsal CA1 neurons and
that HCN channels represent a potential target for the treatment of major
depressive disorder.
PMID- 28416810
TI - The joint impact of cognitive performance in adolescence and familial cognitive
aptitude on risk for major psychiatric disorders: a delineation of four potential
pathways to illness.
AB - How do joint measures of premorbid cognitive ability and familial cognitive
aptitude (FCA) reflect risk for a diversity of psychiatric and substance use
disorders? To address this question, we examined, using Cox models, the
predictive effects of school achievement (SA) measured at age 16 and FCA-assessed
from SA in siblings and cousins, and educational attainment in parents-on risk
for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four
developmental patterns emerged. In the first, risk was predicted jointly by low
levels of SA and high levels of FCA-that is a level of SA lower than would be
predicted from the FCA. This pattern was strongest in autism spectrum disorders
and schizophrenia, and weakest in bipolar illness. In these disorders, a
pathologic process seems to have caused cognitive functioning to fall
substantially short of familial potential. In the second pattern, seen in the
internalizing conditions of major depression and anxiety disorders, risk was
associated with low SA but was unrelated to FCA. Externalizing disorders-drug
abuse and alcohol use disorders-demonstrated the third pattern, in which risk was
predicted jointly by low SA and low FCA. The fourth pattern, seen in eating
disorders, was directly opposite of that observed in externalizing disorders with
risk associated with high SA and high FCA. When measured together, adolescent
cognitive ability and FCA identified four developmental patterns leading to
diverse psychiatric disorders. The value of cognitive assessments in psychiatric
research can be substantially increased by also evaluating familial cognitive
potential.
PMID- 28416811
TI - Gene deficiency and pharmacological inhibition of caspase-1 confers resilience to
chronic social defeat stress via regulating the stability of surface AMPARs.
AB - Both inflammatory processes and glutamatergic systems have been implicated in the
pathophysiology of mood-related disorders. However, the role of caspase-1, a
classic inflammatory caspase, in behavioral responses to chronic stress remains
largely unknown. To address this issue, we examined the effects and underlying
mechanisms of caspase-1 on preclinical murine models of depression. We found that
loss of caspase-1 expression in Caspase-1-/- knockout mice alleviated chronic
stress-induced depression-like behaviors, whereas overexpression of caspase-1 in
the hippocampus of wild-type (WT) mice was sufficient to induce depression- and
anxiety-like behaviors. Furthermore, chronic stress reduced glutamatergic
neurotransmission and decreased surface expression of glutamate receptors in
hippocampal pyramidal neurons of WT mice, but not Caspase-1-/- mice. Importantly,
pharmacological inhibition of caspase-1-interleukin-1beta (IL-1beta) signaling
pathway prevented the depression-like behaviors and the decrease in surface
expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
(AMPARs) in stressed WT mice. Finally, the effects of chronic stress on both
depression- and anxiety-like behaviors can be mimicked by exogenous
intracerebroventricular (i.c.v.) administration of IL-1beta in both WT and
Caspase-1-/- mice. Taken together, our findings demonstrate that an increase in
the caspase-1/IL-1beta axis facilitates AMPAR internalization in the hippocampus,
which dysregulates glutamatergic synaptic transmission, eventually resulting in
depression-like behaviors. These results may represent an endophenotype for
chronic stress-induced depression.
PMID- 28416812
TI - A new locus regulating MICALL2 expression was identified for association with
executive inhibition in children with attention deficit hyperactivity disorder.
AB - Impaired executive inhibition is a core deficit of attention deficit
hyperactivity disorder (ADHD), which is a common childhood-onset psychiatric
disorder with high heritability. In this study, we performed a two-stage genome
wide association study of executive inhibition in ADHD in Han Chinese. We used
the Stroop color-word interference test to evaluate executive inhibition. After
quality control, 780 samples with phenotype and covariate data were included in
the discovery stage, whereas 922 samples were included in the replication stage.
We identified one new significant locus at 7p22.3 for the Stroop word
interference time (rs11514810, P=3.42E-09 for discovery, P=0.01176 for
replication and combined P=5.249E-09). Regulatory feature analysis and expression
quantitative trait loci (eQTL) data showed that this locus contributes to MICALL2
expression in the human brain. Most genes in the network interacting with MICALL2
were associated with psychiatric disorders. Furthermore, hyperactive-impulsive
like behavior was induced by reducing the expression of the zebrafish gene that
is homologous to MICALL2, which could be rescued by tomoxetine (atomoxetine), a
clinical medication for ADHD. Our results suggested that MICALL2 is a new
susceptibility gene for executive inhibition deficiency related to hyperactive
impulsive behavior in ADHD, further emphasizing the possible role of
neurodevelopmental genes in the pathogenic mechanism of ADHD.
PMID- 28416814
TI - ISMEJ turns 10: tracking rapid progress in microbial ecology.
PMID- 28416813
TI - Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids
interactively modulate working memory-related hippocampal function in women: a
multimodal neuroimaging study.
AB - Preclinical evidence suggests that the actions of ovarian steroid hormones and
brain-derived neurotrophic factor (BDNF) are highly convergent on brain function.
Studies in humanized mice document an interaction between estrus cycle-related
changes in estradiol secretion and BDNF Val66Met genotype on measures of
hippocampal function and anxiety-like behavior. We believe our multimodal imaging
data provide the first demonstration in women that the effects of the BDNF
Val/Met polymorphism on hippocampal function are selectively modulated by
estradiol. In a 6-month pharmacological hormone manipulation protocol, healthy,
regularly menstruating, asymptomatic women completed positron emission tomography
(PET) and functional magnetic resonance imaging (fMRI) scans while performing the
n-back working memory task during three hormone conditions: ovarian suppression
induced by the gonadotropin-releasing hormone agonist, leuprolide acetate;
leuprolide plus estradiol; and leuprolide plus progesterone. For each of the
three hormone conditions, a discovery data set was obtained with oxygen-15 water
regional cerebral blood flow PET in 39 healthy women genotyped for BDNF Val66Met,
and a confirmatory data set was obtained with fMRI in 27 women. Our results, in
close agreement across the two imaging platforms, demonstrate an ovarian hormone
by-BDNF interaction on working memory-related hippocampal function (PET:
F2,37=9.11, P=0.00026 uncorrected, P=0.05, familywise error corrected with small
volume correction; fMRI: F2,25=5.43, P=0.01, uncorrected) that reflects
differential hippocampal recruitment in Met carriers but only in the presence of
estradiol. These findings have clinical relevance for understanding the
neurobiological basis of individual differences in the cognitive and behavioral
effects of ovarian steroids in women, and may provide a neurogenetic framework
for understanding neuropsychiatric disorders related to reproductive hormones as
well as illnesses with sex differences in disease expression and course.
PMID- 28416815
TI - In situ programming of leukaemia-specific T cells using synthetic DNA
nanocarriers.
AB - An emerging approach for treating cancer involves programming patient-derived T
cells with genes encoding disease-specific chimeric antigen receptors (CARs), so
that they can combat tumour cells once they are reinfused. Although trials of
this therapy have produced impressive results, the in vitro methods they require
to generate large numbers of tumour-specific T cells are too elaborate for
widespread application to treat cancer patients. Here, we describe a method to
quickly program circulating T cells with tumour-recognizing capabilities, thus
avoiding these complications. Specifically, we demonstrate that DNA-carrying
nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T-cell
nuclei, thereby bringing about long-term disease remission. These polymer
nanoparticles are easy to manufacture in a stable form, which simplifies storage
and reduces cost. Our technology may therefore provide a practical, broadly
applicable treatment that can generate anti-tumour immunity 'on demand' for
oncologists in a variety of settings.
PMID- 28416816
TI - Scalable electrophysiology in intact small animals with nanoscale suspended
electrode arrays.
AB - Electrical measurements from large populations of animals would help reveal
fundamental properties of the nervous system and neurological diseases. Small
invertebrates are ideal for these large-scale studies; however, patch-clamp
electrophysiology in microscopic animals typically requires invasive dissections
and is low-throughput. To overcome these limitations, we present nano-SPEARs:
suspended electrodes integrated into a scalable microfluidic device. Using this
technology, we have made the first extracellular recordings of body-wall muscle
electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also
use nano-SPEARs to record from multiple animals in parallel and even from other
species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish
the first electrophysiological phenotypes for C. elegans models for amyotrophic
lateral sclerosis and Parkinson's disease, and show a partial rescue of the
Parkinson's phenotype through drug treatment. These results demonstrate that nano
SPEARs provide the core technology for microchips that enable scalable, in vivo
studies of neurobiology and neurological diseases.
PMID- 28416817
TI - Controlling propagation and coupling of waveguide modes using phase-gradient
metasurfaces.
AB - Research on two-dimensional designer optical structures, or metasurfaces, has
mainly focused on controlling the wavefronts of light propagating in free space.
Here, we show that gradient metasurface structures consisting of phased arrays of
plasmonic or dielectric nanoantennas can be used to control guided waves via
strong optical scattering at subwavelength intervals. Based on this design
principle, we experimentally demonstrate waveguide mode converters, polarization
rotators and waveguide devices supporting asymmetric optical power transmission.
We also demonstrate all-dielectric on-chip polarization rotators based on phased
arrays of Mie resonators with negligible insertion losses. Our gradient
metasurfaces can enable small-footprint, broadband and low-loss photonic
integrated devices.
PMID- 28416819
TI - Cassava haplotype map highlights fixation of deleterious mutations during clonal
propagation.
AB - Cassava (Manihot esculenta Crantz) is an important staple food crop in Africa and
South America; however, ubiquitous deleterious mutations may severely decrease
its fitness. To evaluate these deleterious mutations, we constructed a cassava
haplotype map through deep sequencing 241 diverse accessions and identified >28
million segregating variants. We found that (i) although domestication has
modified starch and ketone metabolism pathways to allow for human consumption,
the concomitant bottleneck and clonal propagation have resulted in a large
proportion of fixed deleterious amino acid changes, increased the number of
deleterious alleles by 26%, and shifted the mutational burden toward common
variants; (ii) deleterious mutations have been ineffectively purged, owing to
limited recombination in the cassava genome; (iii) recent breeding efforts have
maintained yield by masking the most damaging recessive mutations in the
heterozygous state but have been unable to purge the mutation burden; such
purging should be a key target in future cassava breeding.
PMID- 28416820
TI - Contrasting evolutionary genome dynamics between domesticated and wild yeasts.
AB - Structural rearrangements have long been recognized as an important source of
genetic variation, with implications in phenotypic diversity and disease, yet
their detailed evolutionary dynamics remain elusive. Here we use long-read
sequencing to generate end-to-end genome assemblies for 12 strains representing
major subpopulations of the partially domesticated yeast Saccharomyces cerevisiae
and its wild relative Saccharomyces paradoxus. These population-level high
quality genomes with comprehensive annotation enable precise definition of
chromosomal boundaries between cores and subtelomeres and a high-resolution view
of evolutionary genome dynamics. In chromosomal cores, S. paradoxus shows faster
accumulation of balanced rearrangements (inversions, reciprocal translocations
and transpositions), whereas S. cerevisiae accumulates unbalanced rearrangements
(novel insertions, deletions and duplications) more rapidly. In subtelomeres,
both species show extensive interchromosomal reshuffling, with a higher tempo in
S. cerevisiae. Such striking contrasts between wild and domesticated yeasts are
likely to reflect the influence of human activities on structural genome
evolution.
PMID- 28416821
TI - Pathogenic variants that alter protein code often disrupt splicing.
AB - The lack of tools to identify causative variants from sequencing data greatly
limits the promise of precision medicine. Previous studies suggest that one-third
of disease-associated alleles alter splicing. We discovered that the alleles
causing splicing defects cluster in disease-associated genes (for example,
haploinsufficient genes). We analyzed 4,964 published disease-causing exonic
mutations using a massively parallel splicing assay (MaPSy), which showed an 81%
concordance rate with splicing in patient tissue. Approximately 10% of exonic
mutations altered splicing, mostly by disrupting multiple stages of spliceosome
assembly. We present a large-scale characterization of exonic splicing mutations
using a new technology that facilitates variant classification and keeps pace
with variant discovery.
PMID- 28416823
TI - [Identification of a new pro-invasion factor in tumor microenvironment: progress
in function and mechanism of extracellular ATP].
AB - Up to 90% of all cancer related morbidity and mortality can be attributed to
metastasis. In recent years the study of tumor microenvironment, its cellular and
molecular components, and how they can affect neoplastic progression toward
metastasis, has become a hot focus in cancer research. Accumulated evidence shows
that the formation of metastasis is a multi-step sequential process, in which,
the tumor cells continuously interact with the host microenvironment. Host
derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines,
etc. together with different types of host cells, play important roles in the
tumor progression towards metastasis. The interaction between the tumor cells and
host microenvironment determines the fate of metastasis. The reveal of this
interaction mechanism provides us an opportunity to find effective mode of
interference and develop novel anti-metastasis drugs. In this review, we have
summarized our work on a new pro-invasion factor identified in tumor
microenvironment and how it affects tumor invasion and metastass. Adenosine
triphosphate (ATP), the key intracellular energy currency, accumulates within the
tumor microenvironment and is closely involved in cancer cell metabolism and in
antitumor immunity. The established role of ATP as a growth modulator and a
proinflammatory mediator endues ATP and other purines with potential players in
host-tumor interaction. Our study demonstrated that extracellular ATP stimulated
human cancer invasion in in vitro tests. Increased migration and invasive ability
across Matrigel was observed in some human carcinoma cell lines, including the
prostate, breast, colon, melanoma and lung, when stimulated with ATP or its
analogues. ATP enhanced the motility of cancer cells via increasing the amount
and length of lamellipodia and filopodia, which were necessary for the cell
motility. Significant increase in Rac1 and Cdc42 activities was observed. Using
cDNA microarray we found that the expression of a panel of invasion/metastasis
related genes was significantly changed, including the increased expression of
interleukin (IL)-8 and matrix metalloproteinase-3 (MMP-3) after ATP treatment.
Changes of some epithelial-mesenchymal transition (EMT)-related factors were also
observed, including the increase of snail, decrease of E-cadherin and claudin-1.
Multiple P2Y receptors subtypes were expressed on tumor cells, but P2Y2 and P2X7
receptors were found to be mainly responsible for the pro-invasive effect of ATP.
Down-regulation of either P2Y2 or P2X7 abolished ATP effect on cancer invasion
and expression of EMT/invasion-related genes. Further, we found that P2Y2
receptor trans-activated with epidermal growth factor receptor (EGFR) and co
activated extracellular regulated protein kinases (ERK1/2) signaling pathway,
which was involved in regulating expression of EMT and other related genes. In
nude mice experiment, the pro-invasive effect of ATP was further confirmed. In
summary, our results reveal that ATP is a potential pro-invasive factor in tumor
microenvironment. P2Y2/P2X7 receptors act as a mediator in the regulation of ATP
induced EMT and invasion of cancer cells. Given that tumor microenvironment is
rich in ATP and other purines, we hypothesize that ATP might be a potential
invasion stimulator in tumor microenvironment. Blocking ATP receptor might be a
therapeutic target on cancer.
PMID- 28416822
TI - Identification of six new genetic loci associated with atrial fibrillation in the
Japanese population.
AB - Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To
investigate genetic loci associated with atrial fibrillation in the Japanese
population, we performed a genome-wide association study (GWAS) that included
8,180 atrial fibrillation cases and 28,612 controls with follow-up in an
additional 3,120 cases and 125,064 controls. We replicated previously reported
loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2,
NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated
with atrial fibrillation in the Japanese population after comparing our data to
those from individuals of European ancestry, suggesting that there might be
different genetic factors affecting susceptibility across ancestry groups. Our
study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant
to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in
axon guidance also suggested a role in disease pathogenesis. Our findings may
contribute to a better understanding of atrial fibrillation susceptibility and
pathogenesis.
PMID- 28416824
TI - [Gait analysis at the early stage after direct anterior approach in total hip
arthroplasty].
AB - OBJECTIVE: To evaluate the result of operation and gait analysis at the early
stage after direct anterior approach (DAA) in total hip arthroplasty (THA).
METHODS: In this study, 20 patients who suffered from necrosis of femoral head or
developmental dysplasia of the hip were scheduled to undergo THA. The basic
information and visual analogue scale (VAS) score, Harris score before and after
surgery were recorded. All of the patients finished the gait analysis before the
surgery and 6 weeks and 12 weeks after the surgery, the data were compared with
those of normal adult people. RESULTS: Their hospital stay after the operation
was 3.3 d, the VAS score after the operation was no more than 4 points, the
positions of prosthesis were satisfactory, and there was no dislocation. The gait
analysis results contained step speed, stride, the range of motion (ROM) of hip
and knee. The step speed before the surgery (preoperation, Pre) was 0.64 m/s, 6
weeks after the surgery (6W) was 0.77 m/s, 12 weeks after the surgery (12W) was
1.07 m/s, and the control group was 1.19 m/s. The stride at Pre, 6W, 12W, and
control group were 43.15 steps/min, 51.42 steps/min, 55.52 steps/min, and 57.15
steps/min, respectively. The ROM of hip joint at Pre, 6W, 12W, and control group
were 31.00 degrees , 39.62 degrees , 40.40 degrees , and 45.67 degrees ,
respectively. The ROM of knee joint at Pre, 6W, 12W, and control group were 50.52
degrees , 59.28 degrees , 67.29 degrees , and 70.42 degrees , respectively. The
results of the gait analysis showed that the gait recovery after the direct
anterior total hip arthroplasty was very fast and at the 12th week after surgery
the gait of the patients was close to the normal adult people. CONCLUSION: The
direct anterior approach is one of the choosable approach of the THA, and this
kind of surgery has a better recovery of gait after the operation, and at the end
of 12 weeks after the surgery the gait is very close to the normal adult people.
But we also need more studies to prove this conclusion.
PMID- 28416818
TI - Large-scale analyses of common and rare variants identify 12 new loci associated
with atrial fibrillation.
AB - Atrial fibrillation affects more than 33 million people worldwide and increases
the risk of stroke, heart failure, and death. Fourteen genetic loci have been
associated with atrial fibrillation in European and Asian ancestry groups. To
further define the genetic basis of atrial fibrillation, we performed large
scale, trans-ancestry meta-analyses of common and rare variant association
studies. The genome-wide association studies (GWAS) included 17,931 individuals
with atrial fibrillation and 115,142 referents; the exome-wide association
studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases
and 132,086 referents. We identified 12 new genetic loci that exceeded genome
wide significance, implicating genes involved in cardiac electrical and
structural remodeling. Our results nearly double the number of known genetic loci
for atrial fibrillation, provide insights into the molecular basis of atrial
fibrillation, and may facilitate the identification of new potential targets for
drug discovery.
PMID- 28416825
TI - [Comparison of efficacy and safety between the anterior and the posterior
approaches to total hip arthroplasty].
AB - OBJECTIVE: To compare the efficacy and safety between direct anterior approach
(DAA) and posterior approach (PA) in total hip arthroplasty. METHODS: This study
evaluated postoperative results of 92 consecutive total hip arthroplasties
performed by a single surgeon; 44 from the DAA, and 48 from PA. The age, body
mass index, operation time, blood loss, hospital stay, positioning of the
artificial hip, postoperative Harris score and postoperative complications were
recorded and analyzed. RESULTS: Both the average age of the patients separately
(58.0+/-11.9) years in DAA group and (61.0+/-10.4) years in PA group and the body
mass index (25.1+/-3.7) in DAA group and (24.7+/-3.3) in PA group, showed no
significant difference between the two groups. The DAA group had significantly
reduced the hospital stay (3.8+/-1.7) days vs.(4.9+/-2.3) days for the PA group
(P<0.05) and operation time was (76.0+/-17.4) min in DAA group, and (71.0+/-14.3)
min in PA group (P>0.05). The amount of blood loss: in group DAA (238.0+/-55.3)
mL, and in group PA (387.0+/-61.2) mL (P<0.05). There was no statistical
difference in the positioning of the artificial hip: the cup anteversion in DAA
group and PA group was 17.3 degrees +/-5.3 degrees vs. 18.6 degrees +/- 5.1
degrees , the cup inclination was 38.5 degrees +/-5.7 degrees vs. 37.7 degrees
+/-5.2 degrees . In DAA group, there was significantly less use of assistive
devices [(24.6+/-7.8) d vs. (31.7+/-10.2) d, P<0.05], and the pain was
significantly lower. Harris score at the end of 6 weeks of the follow-up: in DAA
group 85.7+/-5.4, and in PA group 81.3+/-6.1 (P<0.05); at the end of the last
follow-up: in DAA group 93.4+/-4.7, and in PA group 92.3+/-5.3 (P>0.05).
Complications were encountered in the two groups. There were two intraoperative
complications (4.4%), 1 great trochanter fracture and 1 lateral cutaneous nerve
injury in DAA group. No dislocation was observed in DAA group. One dislocations
and 1 groin pain were recorded in PA group. No prosthesis loosening, deep vein
thrombosis, sciatic nerve injury and other complications occurred in the two
groups. CONCLUSION: Total hip arthroplasty using the anterior approach allows for
superior recovery and better stability.
PMID- 28416826
TI - [Surgical technique and early clinical outcomes of direct anterior approach to
total hip arthroplasty].
AB - OBJECTIVE: To describe the surgical technique of direct anterior approach to
total hip arthroplasty and to report the early clinical outcomes. METHODS: A
series of 100 consecutive, unselected patients who had 116 primary total hip
arthroplasty surgeries (16 bilateral) done through direct anterior approach from
March 11 2015 to June 21 2016 was reviewed. There were 50 male patients and 50
female patients. The average patient age was 51 years, and the average body mass
index was 24.69 kg/m2. The preoperative diagnosis included avascular necrosis of
femoral head, hip osteoarthritis, osteoarthritis secondary to acetabular
dysplasia, sequelae of hip old infection, ankylosing spondylitis, rheumatoid
arthritis and avascular necrosis of femoral head after cannulated screws fixation
of femoral neck fracture. There were 7 hips which had surgical history prior to
the index hip arthroplasty, including 3 cases with bone graft treatment for
avascular necrosis of femoral head through Smith-Peterson approach, 2 cases with
acetabular shelf procedures for acetabular dysplasia through Smith-Peterson
approach, and 2 cases with cannulated screws fixation for femoral neck fracture
(internal fixation residual). All were uncemented hips. The stems used in this
study included 67 Triloc stems (DePuy company, USA), 45 Corail stems (DePuy
company, USA), 2 Accolade stems (Stryker company, USA), 1 Synergy stem (Smith
Nephew company, USA) and 1 Polarstem (Smith-Nephew company, USA). RESULTS: The
average follow up period was 8.5 months, the average incision scar length was 10
cm, and the average postoperative Harris score was 93.62. There was 95%
postoperative leg length discrepancy within 3 mm. The average cup inclination
angle was 38.7 degrees with 94.8% in the range of 30 degrees to 50 degrees .
The average cup anteversion angle was 14.3 degrees with 94.2% within the target
range of 5 degrees to 25 degrees .The were 15 (12.9%) operative complications,
including two femoral perforations (changing stem from Triloc to Corail), three
calcar fractures (treated with cerclage wires), four greater trochanter fractures
(2 were treated wire tension band, and 2 nondisplaced fractures untreated), one
deep infection (debridement and retaining of the prothesis), one superficial
infection (debridement), one hematoma and three wound healing complications
(debridement). All the complications were successfully treated without any
sequelae at the end of the latest follow-up. There was no postoperative
dislocation. There was no major nerve and vascular injuries. There were 35 cases
(30.2%) reporting symptoms of lateral femoral cutaneous nerve palsy. CONCLUSION:
Direct anterior approach to total hip arthroplasty allows accurate and
reproducible cup orientation positioning and leg length restoration and decreases
the risk of postoperative dislocation, which is helpful for early rapid
postoperative recovery.
PMID- 28416827
TI - [Comparison of the effects of total hip arthroplasty via direct anterior approach
and posterolateral piriformis-sparing approach].
AB - OBJECTIVE: To compare the clinical effects of direct anterior approach (DAA) and
posterolateral piriformis-sparing approach (Mis-PLA) for minimally invasive
surgery of total hip arthroplasty. METHODS: The patients who had total hip
arthroplasty from March 2015 to February 2016 were randomly divided into 2
groups: DAA group and Mis-PLA group. In the study, 43 patients (45 hips) were
performed with total hip replacement via the direct anterior approach (DAA
group). As comparison, 39 patients (42 hips) were performed with total hip
replacement via the posterolateral piriformis-sparing approach (Mis-PLA group) at
the same period. DAA group: 27 male patients (27 hips), and 16 female patients
(18 hips), with an average age of (57.4+/-7.3) years, preoperative Harris score
(41.4+/-8.7), body mass index (BMI) (24.3+/-2.2) kg/m2; Mis-PLA group: 25 male
patients (26 hips), 14 female patients (16 hips), with an average age of (59.2+/
7.3) years, preoperative Harris score (39.6+/-8.4), BMI (24.7+/-2.5) kg/m2. The
length of incision, operation time, blood loss, postoperative Harris score were
observed and specially the hip functional recovery was fully assessed. RESULTS:
(1) All the incisions healed by first intention. No complications were found in
both groups. The length of incision:DAA group: (9.2+/-0.7) cm and Mis-PLA group:
(9.5+/-0.6) cm. No statistical significant differences were found (P=0.053). The
operation time:DAA group (74.3+/-10.1) min and Mis-PLA group (37.5+/-4.3) min,
which showed statistically significant differences (P<0.01). Blood loss: DAA
group (229.6+/-79.2) mL and Mis-PLA group (215.7+/-56.0) mL. No statistical
significant differences were found (P=0.366). (2) The patients in both groups
were followed up for 6-12 months. The Harris hip scores for 6 weeks' follow-up:
(85.5+/-4.1) in DAA group and (79.0+/-4.4) in Mis-PLA group, which indicated
statistically significant differences (P<0.01). The Harris scores for the 6-month
follow-up: (94.3+/-2.7) in DAA group and (95.2+/-1.9) in Mis-PLA group. No
statistically significant differences were found (P=0.125). The basic daily hip
function analysis for the 6-week follow-up: walking speed: no statistically
significant differences were found between the two groups (P=0.298); Climbing
stairs: Mis-PLA group' outcome was better than DAA group's with statistical
differences (P=0.047); Circling, sitting and wearing shoes and socks: outcomes in
DAA group exceeded Mis-PLA group's with statistically significant differences
(P<0.01, P=0.016, P<0.01). CONCLUSION: Total hip arthroplasty through either DAA
or Mis-PLA approaches could result in very satisfactory clinical effect.
Comparing with DAA, Mis-PLA requires less operation time, shorter learning
curve,which indicates that it is a relatively safer approach. The advantages of
total hip arthroplasty through direct anterior approach lie in less positional
limitation in the early stage of postoperative period, as well as a faster
recovery of hip function.
PMID- 28416828
TI - [Application of bilateral direct anterior approach total hip arthroplasty: a
report of 22 cases].
AB - OBJECTIVE: To analyze the operation technique and the methods to avoid early
complications on the learning curve for bilateral direct anterior approach (DAA)
total hip arthroplasty (THA). METHODS: We retrospectively studied a series of
continued cases with bilateral avascular necrosis of the femoral head (AVN) or
degenerative dysplastic hip and rheumatoid arthritis that were treated by DAA THA
in Beijing Jishuitan Hospital. A total of 22 patients with 44 hips were analyzed
from June 2014 to August 2016 in this study. There were 17 males and 5 females,
and the median age was 48 years (range: 34-67 years). All the surgery was done by
DAA method by two senior surgeons. The clinic characters, early surgery treatment
results and complications were analyzed. RESULTS: We used the cementless stems in
all the cases. The average operating time was (167+/-23) min; the average blood
loss was (775+/-300) mL;the blood transfusion was in average (327+/-341) mL; the
wound drainage in average was (111+/-73) mL. Most of the patients could move out
of the bed by themselves on the first day after operation, 5 patients could walk
without crutches on the first operating day, and 13 patients could squat on the
third days after operation. The patients were discharged averagely 4 days after
operation. We followed up all the patients for averagely 16 months (range: 8-24
months). There was no loosening or failure case in the latest follow up. In the
study, 2 patients had great trochanter fracture, 2 patients had thigh pain, 4
patients had lateral femoral cutaneous nerve palsy, and 3 patients had muscle
damage. The Harris scores were improved from 29+/-8 preoperatively to 90+/-3
postoperatively (P<0.01). CONCLUSION: The DAA THA can achieve faster recovery and
flexible hip joint after operation. However it is a kind of surgery with high
technique demanding. Carefully selected patients, and skilled technique, can help
the surgeon avoid the early complications. It is associated with high
complication rate in the learning curve for bilateral DAA THA.
PMID- 28416829
TI - [Clinical characteristics and prognosis of cultured negative pyogenic
spondylitis].
AB - OBJECTIVE: There are limited data describing the clinical characteristics and
prognosis of culture negative pyogenic spondylitis. The aim of this study was to
investigate the treatment, prognosis and clinical characteristics of culture
negative pyogenic spondylitis. METHODS: A retrospective study reviewed 74
patients who were diagnosed with spondylitis in Peking University First Hospital
from January 2010 to December 2015. A total of 27 patients suffered from pyogenic
spondylitis. According to the pathogenic culture results, the patients were
divided into two groups: culture negative group and culture positive group. The
clinical characteristics and treatment outcomes between the two groups were
compared. RESULTS: The elder were more vulnerable to pyogenic spondylitis, and of
the 27 patients, 12 patients were female and 15 male. All patients had no history
of administration of antibiotics prior to obtaining culture samples. A causative
germ was identified in 14/27 patients (51.9%) with Staphylococcus aureus being
the most common pathogen. There was no significant difference between the two
groups in the patient's age, gender, visual analogue score (VAS), predisposing
factor, clinical symptom, sign and spinal segment (P>0.05). Erythrocyte
sedimentation rate (ESR) (P=0.056) and C-reactive protein (CRP) (P=0.040) of
culture negative group were lower in contrast to culture positive group. The
incidence of vertebral abscess in culture negative group was higher than in
culture positive group (P=0.046). After treatment, ESR dropped almost equally in
both groups, and CRP dropped faster in the culture positive group (P=0.192). At
last, there was no significant difference between the two groups in hospital
stay, pain relief, open debridement operation rate, and recurrence rate of
infection. CONCLUSION: ESR and CRP of the culture negative patient were lower
than those of the culture positive patient, and the incidence rate of
paravertebral abscess was higher than that of the culture positive patient. After
administration of antibiotics, there was no significant difference between the
two groups in duration of antibiotics, open debridement operation rate and
recurrence rate of infection. So, culture negative may not necessarily be a
negative prognostic factor for pyogenic spondylitis. However, we should watch out
for the drug resistant bacteria or double infection, due to the long term use of
wide-spectrum antibiotic in culture negative patients.
PMID- 28416830
TI - [Analysis on the causes of unscheduled suspensions of knee and hip arthroplasty].
AB - OBJECTIVE: To analyze and summarize the causes of unscheduled suspension of knee
and hip arthroplasty and to provide the method for optimizing the patient's
preoperative management and improving the efficiency of medical resources as well
as the patient's satisfaction. METHODS: The data for this report was
retrospectively collected from September 2013 to August 2014 in our hospital,
from cases of knee and hip arthroplasty that were suspended before the scheduled
operation time. Acquisition data from the collected cases including the patients'
gender, age and the surgical procedure. At the same time, the suspension reasons
were recorded and analyzed. All the decisions of suspension was made by the
surgeons and the anesthesiologists according to the abnormal result of
preoperative examinations, after communicating with the patients and their
families and obtaining their understandings. RESULTS: In the collecting period,
our department scheduled 1 146 cases of knee and hip arthroplasty, among which 1
003 were completed, 143 suspended (12.5% suspension rate). Among the causes of
suspension, the top four common causes were cardiovascular disease (44/143, 31%),
other infections (20/143, 14%), bacteriuria (18/143, 13%) and inappropriate
surgical indication (16/143, 11%). Other causes include surgeon's reason, Blood
system abnormalities, high inflammatory index, deep vein thrombosis, other
diseases uncontrolled, abnormal liver function and poor diabetes mellitus
control, etc. For the rate of suspension, there was no significant difference
between the patients with different genders (male: 15.0%, and female: 11.7%,
P=0.149), or age (<=50 years: 13.0%; 51-65 years: 11.6%; 66-80 years 13.3%; >80
years 11.1%; P=0.864). However compared with knee arthroplasty, hip arthroplasty
had a higher suspension rate (knee arthroplasry 11.1%, hip arthroplasry 16.1%,
P=0.021). CONCLUSION: It is important to educate and manage the patients before
their knee and hip arthroplasty. Through clear diagnosis, detailed medical
history analysis careful physical examination, and targeted outpatient
examinations and tests for which priority was focused on cardiovascular or other
system diseases we could minimize the occurrence of operative suspension post
hospitalization, therefore improving the efficiency of the use of medical
resources.
PMID- 28416831
TI - [Morphology character and reduction methods of sagittally unstable
intertrochanteric fractures].
AB - OBJECTIVE: To investigate the morphology character of sagittally unstable
intertrochanteric fractures and reduction methods. METHODS: A retrospective study
was used to analyze the clinical data of sagittally unstable intertrochanteric
fractures cases, which were treated with proximal femoral nail anti-rotation
(PFNA) fixation from March 2009 to June 2016. In the study, 36 cases were
followed up completely, in which 17 cases accepted open reduction, and the other
19 cases accepted minimally invasive reduction. The operation time, amount of
bleeding, the fluoroscopy times, postoperative radiographic measurements, such as
tip-apex distance (TAD) and sliding distance of the spiral screw, and hip Harris
scores were analyzed. The morphology character of the fractures was documented
and investigated. RESULTS: The average follow-up time was 15 months. The amount
of bleeding of the open reduction group was (170.5+/-19.7) mL, and the amount of
bleeding of the minimally invasive group was (54.7+/-12.5) mL. The amount of
bleeding of the minimally invasive group was significantly less than that of the
open reduction group (P<0.001). Between the two groups, there were no significant
differences in other evaluation parameter, including operation time (P=0.054),
the fluoroscopy times (P=0.053), fracture healing time (P=0.305), postoperative
radiographic measurements, such as TAD (P=0.317) and sliding distance of the
spiral screw (P=0.206), and hip Harris scores (P=0.459). In regard to morphology
character of the fractures, the proximal anterior unstable fractures with
separation displacement were more common than the proximal posterior unstable
fractures with impaction. The characteristic feature of the proximal anterior
unstable fractures was the proximal anterior and medial long oblique fracture,
and a V shape cortical defect in the distal fracture fragment on the externally
rotation X-ray. CONCLUSION: Sagittally unstable intertrochanteric fractures can
be divided into the proximal anterior unstable fractures with separation
displacement, and the proximal posterior unstable fractures with impaction. The
two types have their own morphology character individually. The reduction should
be performed by minimally invasive techniques.
PMID- 28416832
TI - [Minimally invasive plate osteosynthesis for treatment of proximal humeral
fractures through anterolateral acromial approach].
AB - OBJECTIVE: To investigate the feasibility, surgical technique and effect of
osteosynthesis for proximal humerus fractures through the minimal incision
anterolateral acromion. METHODS: In this study, 32 patients of proximal humeral
fractures were selected and treated through the minimal incision antero-lateral
acromion between January 2012 and October 2014. Of these patients, there were 19
males and 13 females, with mean age 46 years old (range: 22-78 years). The
mechanism of injury was a trauma of simple fall for 21 patients and motor vehicle
accident for 11 patients. According to Neer classification, 18 cases had two-part
fractures, 12 had three-part fractures, and 2 had four-part fractures. All
patients were sustained operation of open reduction and internal fixation. The
average delay between trauma and surgery was 4 d (0.5-10.0 d). The operations
were performed in invariable operating room with general anesthesia. The
fractures were reduced and immobilized with anatomical locking plate through the
minimal incision anterolateral acromion during operation. Patients were received
passive motion after operation. RESULTS: All the 32 cases were followed up
ranging from 3 to 34 months with an average of 11 months. All the fractures were
healed. There was neither failure of internal fixation nor incision infection
case. The functional results of the shoulder, according to Constant-Murley score
was on an average 86 (range: 69-100). CONCLUSION: The treatment for proximal
humeral fractures through the minimal incision anterolateral acromion approach is
a feasible and effective method, which shows good results for treating proximal
humerus fractures with correct indication. There are several advantages compared
with conventional deltopectoral approach. They are minimal soft tissue
disruption, minimal blood loss and easily to manipulate technique. But it
required selection of indication strictly and surgeon's experience.
PMID- 28416833
TI - [Diagnosis and treatment for the basicervical fractures of the trochanteric
region].
AB - OBJECTIVE: To evaluate the rate of basicervical fractures and document their
diagnosis and treatment. METHODS: From January 2005 to May 2016, 28 basicervical
fractures of the 832 trochanteric fractures were collected and evaluated. The
patients were treated with multiple screws, dynamic hip screw (DHS),
intramedullary nail. Via the operation time, postoperative hospitalization, loss
of blood duration the operation, hidden blood loss, total blood loss, mean union
time and the final follow-up Harris hip score, the characteristics of different
internal fixations were compared and analyzed. RESULTS: The incidence of
basicervical fractures was 3.37% (28/832) in our study. In the intramedullary
nail group (16 patients), the operation time was 55 (20,120) min, the
postoperative hospitalization was 3(2, 7) d, the intraoperative blood loss was 50
(5,100) mL, the hidden blood loss was 533.37 (376.19, 987.15) mL, and the total
blood loss 627.35 (406.19, 1037.16) mL. The union time and final follow-up Harris
score were 6 (3, 9) months and 90.25 (74,100) min. In the DHS group (8 patients),
the operation time was 87.5 (65,115) min, the postoperative hospitalization was
5.5 (2, 17) d, the intraoperative blood loss was 100 (50,300) mL, the hidden
blood loss was 278.11 (202.43, 849.97) mL, and the total blood loss 580.19
(368.55, 899.97) mL . The union time and final follow-up Harris score were 5.5
(4, 12) months and 85.5 (84, 87) min. In the multiple screws group (4 patients),
the operation time was 47.5 (35, 75) min, the postoperative hospitalization was 5
(2, 12) d, the intraoperative blood loss was 20 (2, 70) mL, the hidden blood loss
was 150 (100.00, 412.01) mL, and the total blood loss 195.00 (120.00, 414.01) mL.
The union time and final follow-up Harris score were 4 (4, 6) months and 80 (61,
97) min. The patients treated with multiple screws and intramedullary nail had a
shorter operation time than the DNS group, but no obvious difference was found
between the other two groups (P=0.367). Postoperative hospitalization had no
significant difference among the three groups. The intraoperative bleeding was
more in the DHS group, the other two groups had no significant difference
(P=0.100). However, the hidden blood loss was more in the intramedullary nail
group, the other two groups had no significant difference (P=0.134). The total
blood loss in the intramedullary nail group was more than multiple screw group,
similar to the DHS group (P=0.483). One patient treated with multiple screws
underwent internal fixation failure three months after operation. The mean union
time and final follow-up Harris scores had no significant difference among the
three groups (P>0.05). CONCLUSION: Through this study, we found that the
incidence of basicervical fractures is low. Fractures with no shift can be
confirmed by preoperative X-ray. For displaced fractures, preoperative CT+3D
reconstruction is recommended. Surgical treatment by closed reduction and
internal fixation with DHS or intramedullary nail is shown to be very effective.
PMID- 28416834
TI - [Efficacy of transforaminal endoscopic nerve root decompression in the treatment
of degenerative lumbar spinal stenosis].
AB - OBJECTIVE: To evaluate the feasibility of transforaminal endoscopic nerve root
decompression for degenerative lumbar spinal stenosis (DLSS). METHODS: From July
2011 to April 2016, 96 cases of single segment DLSS were involved. All the
patients had unilateral lower extremity neurological symptoms, signs, neurogenic
intermittent claudication of less than 500 m. Imaging examinations (CT or MRI) or
diagnostic nerve root block confirmed single segment degeneration. The mean age
was (71.6+/-5.4) years, male: 55 cases, female: 41 cases. Their intraoperative
blood loss, operation time, complications, ambulation time and discharge time
were recorded. Leg pain VAS, ODI were used to evaluate the pain and lumbar
function of the patients. The clinical efficacy was evaluated by Nakai
evaluation. RESULTS: All the patients were performed endoscopic decompression of
the lateral recess and nerve root by removing the ventral part of the superior
facet joint, the ligamentum flavum and the intervertebral disc. The decompression
range was from the inferior edge of the upper pedicle to the superior edge of the
lower pedicle. The nerve root was detected to have no compression and the pulse
of nerve root returned to normal. The patient got ambulant on the operation day
and discharged if he had no discomfort symptom. In the study, 68 cases got follow
up. The mean follow-up time was 12.1 months (6-63 months). The VAS at different
follow-up time points was improved relative to the baseline, and the difference
was statistically significant (F=491.60, P<0.001). The ODI at different follow-up
time points was improved relative to the baseline, and the difference was
statistically significant (F=189.91, P<0.001). The excellent and good rates of
Nakai evaluation were 79.4% (excellent in 42 cases, good in 12 cases, fair in 10
cases and poor in 4 cases). The mean intraoperative blood loss was (49.29+/
11.86) mL. The mean operation time was (92.46+/-21.34) min. The mean ambulation
time was 1.8 h. The mean discharge time was 2.3 days. Postoperative epidural
hematoma was found in 1 case. Foot drop was found in 1 case. Second stage open
surgery was performed in 6 cases. CONCLUSION: We can apply transforaminal
endoscopic decompression for the patients of lumbar spinal stenosis who have
unilateral nerve root irritation. Patients with transforaminal endoscopic
decompression can get less surgical trauma, quick recovery and obtain good short
term outcome.
PMID- 28416835
TI - [Polymethylmethacrylate augmentation of bone cement injectable cannulated pedicle
screws was used to treat degenerative lumbar scoliosis with osteoporosis].
AB - OBJECTIVE: To describe the application of polymethylmethacrylate (PMMA)
augmentation of cement-injectable cannulated pedicle screws for the treatment of
degenerative lumbar scoliosis with osteoporosis. METHODS: Retrospective cohort
study was used to compare cement injectable cannulated pedicle screws (CICPs)
group with PMMA augmentation and control group with traditional method in the
correction surgery for Lenke-silva level III and level IV degenerative scoliosis
cases with osteoporosis. Both groups were followed up for 1 year. The clinical
results were assessed by visual analog scale (VAS) of pain on lumbar and lower
limbers, Oswestry disability index (ODI) score and EuroQol-5 dimensions (EQ-5D)
score. The coronal major curve Cobb angel in coronal plane and thoracic kyphosis
Cobb angle, lumbar lordosis Cobb angle and sagittal vertical axis (SVA) in
sagittal plane were tested in whole long spine X ray. The fusion rates were
evaluated by lumbar X ray and dynamic X ray. RESULTS: In this study 34 cases were
enrolled, 15 cases in CICPs group and 19 cases in control group. The general
characteristics including age, gender, weight, height, BMI and BMD were without
statistical difference between the two groups. There were (5.7+/-2.2)PMMA
augmentation screws in CICPs group. The operation time, blood loss and blood
transfusion were higher in CICPs group than in control group, but without
statistical difference. Lumbar VAS, lower limbers VAS, ODI score and EQ-5D were
all better in 1 month postoperation, 6 months postoperation and 1 year
postoperation than in preoperation in both groups. lumbar VAS scores of CICPs
group in 6 months postoperation (CICPs group 3.1+/-1.3 vs. control group 4.4+/
1.4, P<0.01) together with lumbar VAS scores (CICPs group 3.3+/-1.0 vs. control
group 5.2+/-1.4, P<0.01), ODI scores (CICPs group 22.7+/-17.2 vs. control group
31.4+/-18.5, P<0.01) and EQ-5D in 1 year postoperation (CICPs group 2.9+/-2.0 vs.
control group 3.5+/-2.5, P<0.01)were lower than those of control group. The
coronal major curve Cobb angels were all lower in 1 month postoperation, 6 months
postoperation and 1 year postoperation than in preoperation in both groups;
thoracic kyphosis Cobb angle and lumbar lordosis Cobb angle were all higher in 1
month postoperation, 6 months postoperation and 1 year postoperation than in
preoperation in both groups. The coronal major curve Cobb angel was lower in
CICPs group than that in control group in 1 year postoperation (CICPs group 17.6
degrees +/-6.9 degrees vs. control group 21.2 degrees +/-7.2 degrees ,
P<0.01)and thoracic kyphosis Cobb angle was higher in CICPs group than that in
control group in 6 months postoperation (CICPs group -33.5 degrees +/-8.8
degrees vs. control group -28.9 degrees +/-8.3 degrees , P<0.01) and 1 year
postoperation (CICPs group -33.0 degrees +/-8.1 degrees vs. control group -26.3
degrees +/-7.4 degrees , P<0.01) together with lumbar lordosis Cobb angle were
higher in CICPs group than that in control group in 1 year postoperation (CICPs
group 26.4 degrees +/-8.1 degrees vs. control group 22.1 degrees +/-7.3 degrees
, P<0.01). CONCLUSION: Polymethylmethacrylate augmentation of bone cement
injectable cannulated pedicle screws for the treatment of degenerative lumbar
scoliosis with osteoporosis was effective and safe, the short-term clinical
result was good.
PMID- 28416836
TI - [Comparison between flexible laryngeal mask airway and reinforced tracheal tube
used for lumbar vertebral surgery in prone position].
AB - OBJECTIVE: To estimate the safety and feasibility of flexible laryngeal mask
airway (FLMA) for lumbar vertebral surgery in prone position. METHODS: In the
study, 120 adult patients scheduled for lumbar vertebral surgery under
intravenous general anesthesia were divided into group FLMA and reinforced
tracheal tube (RTT) group at random. Heart rate (HR), systolic blood pressure
(SBP) and diastolic blood pressure (DBP) were recorded at the beginning of
anesthesia induction (T0) and on the time of artificial airway intubation (T1), 1
min after intubation (T2), extubation (T3), 1 min after extubation (T4) as well.
The number and time required for intubation were recorded. Peak airway pressure
(PPEAK), airway sealing pressure (PAS) in group FLMA and fiberoptic bronchoscopy
scale (FBS) were recorded after artificial airway intubation, turned over into
prone position and after the operation started, as well as on the time of 1 hour
after the operation started, 2 hours after operation started and when the
operation stopped. Finally, respiratory complications after extubation, including
hypoxemia, laryngospasm, coughing, vomiting, hoarseness, and pharyngalgia, were
observed and whether there was blood or sewage inside and outside the artificial
airway was recorded. RESULTS: There was no difference in the number and time
required for intubation between the two groups (P>0.05). There was no difference
in PPEAK and FBS between the two groups, and also the same at the different time
points in each group (P>0.05). PAS in group FLMA was the same at the diverse time
points during anesthesia (P>0.05) and always higher than PPEAK in the
perioperative period. In group FLMA, there was no difference in HR, SBP and DBP
between the time points of T2 and T1, also of T4 and T3 (P>0.05). In group RTT,
HR, SBP and DBP were significantly higher between the time points of T2 and T1
(P<0.01); SBP was significantly higher between the time points of T4 and T3
(P<0.01), DBP and HR were higher between the time points of T4 and T3 (P<0.05).
SBP in group FLMA was significantly lower than in group RTT at T2 (P<0.01), HR
and DBP were lower than those in group RTT simultaneously (P<0.05). On the time
point of T4, SBP, DBP and HR in group FLMA were lower than those in group RTT
(P<0.05). The incidence of coughing and pharyngalgia after extubation was
significantly lower in group FLMA than in group RTT (P<0.01), with the incidence
of hoarseness was lower in group FLMA than in group RTT (P<0.05). There was no
difference in the incidence of hypoxemia, vomiting and blood seen outside the
cuff between the two groups (P>0.05) while no laryngospasm and sewage seen
outside the artificial airway in each group. CONCLUSION: For suitable patients,
FLMA can be used in mechanical ventilation forlumbar vertebral surgery in prone
position with more stable circulation and less respiratory complications than
RTT. Further clinical validation is needed for the safety of FLMA.
PMID- 28416837
TI - [Clinical comparison of polymethylmethacrylate and bone cement in the treatment
of osteoporotic vertebral compression fractures: a retrospective study].
AB - OBJECTIVE: To analyze the outcomes of patients with osteoporotic vertebral
compression fractures treated with polymethylmethacrylate (PMMA) and GeneX bone
cement in percutaneous kyphoplasty and to provide guidance in selecting the
vertebral filling material for this procedure. METHODS: In this study, 86
patients with osteoporotic vertebral compression fractures treated at Peking
University Third Hospital between June 2012 and June 2013 were retrospectively
analyzed. The patients were followed-up with questionnaires and X-ray and CT
examinations after 1 month, 3 months, 6 months, and 1 year. Postoperative
conditions, including recovery rate of vertebral height, recovery rate of
vertebral Cobb angle, CT data, reductions in visual analogue scale (VAS) and
Oswestry scores, and postoperative complications, were evaluated. The results
were analyzed using SPSS 18.0. RESULTS: According to the rank sum test, there
were significant differences in the recovery rate of vertebral height, vertebral
Cobb angle and vertebral volume between the two groups after 3 months, 6 months,
and 1 year (P<0.05). The GeneX group had greater losses in vertebral height, Cobb
angle and volume than did the PMMA group. The PMMA group had 3 cases of cement
leakage and 1 case of an adjacent vertebral fracture after percutaneous
kyphoplasty. The GeneX group had 2 cases of cement leakage. CONCLUSION: GeneX
bone cement is similar to PMMA in terms of postoperative pain relief. As the
filling material in percutaneous kyphoplasty, it is effective at maintaining
vertebral height, quickly improves strength and stiffness of the vertebral body
and has fewer complications. However, it is not satisfactory in maintaining long
term postoperative vertebral height. GeneX bone cement can be used as the filling
material for patients with osteoporotic vertebral compression fractures in
percutaneous kyphoplasty. Patients with severe osteoporosis and vertebral
compression should be treated with standardized osteoporosis treatment and should
try to avoid early postoperative walking exercises. Sustained vertebral filling
materials, such as PMMA, are more suitable for such patients. Research into
better biodegradable materials is still needed.
PMID- 28416838
TI - [Clinical research on robot-assisted percutaneous pelvic and acetabular screws
surgery].
AB - OBJECTIVE: To evaluate the security and efficiency of a surgical robotic assisted
percutaneous screw fixation for the treatment of pelvic and acetabular fractures.
METHODS: In the study, 12 patients with pelvic and acetabular fractures who were
treated in Beijing Jishuitan Hospital from January to April in 2016 were involved
in this research. The research subjects were randomly divided into two groups:
the experimental group and the control group. Robotic-assisted percutaneous
sacroiliac screw internal fixations were performed under the guidance of
fluoroscopy navigation in the experimental group; in the control group, doctors
operated manually guided by fluoroscopy. Statistical analysis was performed on
the total operation time, the intraoperative fluoroscopy time, the adjustment
numbers of intraoperative guide wires, the excellent rate of screw placement and
the incidence of adverse events in order to evaluate the security and efficiency
of a surgical robotic assisted percutaneous screw fixation for the treatment of
pelvic and acetabular fractures. RESULTS: Eleven screws were placed in 7 patients
from the experimental group, while 7 screws were placed in 5 patients from the
control group in total. All the screw placement positions were satisfactory
according to postoperative CT images. The excellent rates of screw placement
position were 100% in both groups. However, the P value was 0.016 based on the
comparison between the screws' distribution in the two groups which meant that
the screw distribution of the experimental group was better than that of the
control group. The average fluoroscopy time needed for screw insertion was
(7.36+/-2.63) s in the experimental group while (41.80+/-13.99) s in the control
group (P<0.001). This suggested that the difference between the two groups had
statistical significances. Intra-operative fluoroscopy time of the experimental
group was significantly smaller than that of the control group. The number of the
average screw adjustment was (0.36+/-0.48) times in the experimental group while
(9.00+/-3.06) times in the control group (P=0.003). This suggested that the
difference of the number of the guide needle adjustment between the two groups
had statistical significances, and the number of the experimental group was
smaller than that of the control group. The average operation time was (43.86+/
49.06) min in the experimental group while only (29.00+/-12.14) min were needed
in the control group (P=0.528). This suggested that the difference between the
two groups had no statistical significance. That is, the total operation time of
the two groups was equal. All the screws were in satisfactory positions according
to validation results of CT scans. No complications such as screw breaking out
the bone cortex and entering into the knee joint cavity, wound infection
occurred. CONCLUSION: Surgical robots are suitable for robot-assisted
percutaneous screw fixation in pelvic and acetabular fractures. Robot-assisted
treatment of pelvic and acetabular fractures has significant advantages over
manual operations including high accuracy, small perspective radiation, safety
and efficiency.
PMID- 28416839
TI - [A correlation analysis of the ankle CT and ankle fracture classification].
AB - OBJECTIVE: To summarize the CT features of ankle fracture and to analyze the
relationship between the CT images and the most commonly used ankle fracture
classification. METHODS: With 369 cases of adult ankle fractures analyzed
retrospectively, the CT images 1 cm above the ankle joint and its
characteristics, the Danis-Weber classification of ankle fracture were studied,
and so was the relationship between CT images and the fracture classification.
RESULTS: There were 8 forms of CT images. With a, b, and c referred to the
fibular fracture, posterior malleolar fracture and interosseous tibiofibular
ligament (IOL) rupture respectively. 369 CT imges had 40 cases of 0 degree injury
(fibula, posterior malleolus, IOL all intact); 60 cases of Ia degree injury
(fibular fracture, posterior malleolus and IOL intact), 3 cases of Ib degree
injury (fibula intact, posterior malleolus fracture, IOL intact), 26 cases of Ic
degree injury (fibula and posterior malleolus intact, IOL rupture); 163 cases of
IIab degree injury (fibula and posterior malleolus fractures, IOL intact), 6
cases of IIac degree injury (fibular fracture, posterior malleolus intact, IOL
rupture), 61 cases of IIbc degree injury (fibula intact, posterior malleollar
fracture, IOL rupture); 10 cases of III degree injury (fibular fracture,
posterior malleollar fracture and IOL rupture). According to the Danis-Weber
classification, there were 18 cases of type A, 238 cases of type B, 94 cases of
type C, and 19 cases without fibular fracture. The prevalence of IOL rupture were
0, 5.9%, and 88.3% in types A, B, and C respectively. There was a correlation
between the CT image and Danis-Weber classification, the incidence of IOL rupture
was changed with the severity of Danis-Weber classification, and the difference
was statistically significant after the rank correlation test (Spearman R=0.781,
P<0.001). IOL rupture not determined by the fracture classification was found
with the CT images and the incidence was 5.9%. CONCLUSION: Cross-sectional CT
images 1 cm above the ankle joint can clearly determine the IOL injury
preoperatively with a good correlation with the Danis-Weber fracture
classification, IOL rupture unrecognized with the fracture classification can
also be noticed with the CT image.
PMID- 28416840
TI - [B7-H3 silencing inhibits human hematological malignancy xenograft tumor
tumorigenesis and metastasis in nude mice].
AB - OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene
silencing on the tumorigenesis and metastasis of human hematological malignancy
xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR
(qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13
strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which
expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in
U937, Maver and Z138 was performed by lentivirus transduction and the effect of
B7-H3 silencing in stable cell lines was tested by qPCR and FCM. Injecting the
nine groups subcutaneously into the nude mice to establish xenograft models after
dividing the U937, Maver and Z138 into non-infected control group (CON), B7-H3
knockdown group (KD) and negative non-targeted control infected group
(NC),respectively, for detecting the tumorigenicity and metastasis in vivo.
Furthermore, the expression of Ki-67 in xenograft tumors was detected by
immunohistochemistry (IHC). The expression of metalloproteinase 2 (MMP-2) was
detected by western blot. RESULTS: The stable B7-H3 silencing cell lines of U937,
Maver and Z138 were successfully established. Compared with the NC group, the KD
groups of U937, Maver and Z138 had an obviously slower tumor growth. The average
tumor inhibition rates at the end of observation period were 61.83% (F=43.78,
P<0.05), 59.12% (F=36.51, P<0.05) and 67.37% (F=40.29, P<0.05); there was no
significant difference in tumor volume growth between the NC group and the CON
group (P>0.05). The liver distant metastasis of all the xenograft tumor models in
nude mice was the most common and the rates of distant metastasis in KD groups
were significantly lower than that of the corresponding NC groups. The Ki-67
indexes of the KD groups were significantly lower than those of the relative NC
groups in three cell lines (U937: 40.3%+/-5.2% vs. 79.1%+/-6.3%, q=30.31, P<0.05,
Maver: 35.2%+/-6.4% vs. 69.6%+/-5.1%, q=24.82, P<0.05; Z138: 38.4%+/-7.1% vs.
75.7%+/-4.8%, q=28.07, P<0.05); there was no significant difference in the
expression of Ki-67 between the NC group and the CON group (P>0.05). The
expressions of MMP-2 were also significantly lower in the KD groups than in the
NC groups (U937: q=14.59, P<0.05; Maver: q=9.25, P<0.05; Z138: q=11.04, P<0.05);
there was no significant difference in the expression of MMP-2 between the NC
group and the CON group (P>0.05). CONCLUSION: Targeted B7-H3 gene silencing could
inhibit the tumorigenesis and metastasis of human hematological malignancy
xenograft tumor in nude mice. The mechanism may be related to the down-regulation
of Ki-67 and MMP-2.
PMID- 28416841
TI - [Urothelial carcinoma-associated 1 enhances tamoxifen resistance in breast cancer
cells through competitively inhibiting miR-18a].
AB - OBJECTIVE: To investigate how urothelial carcinoma-associated 1 (UCA1) and miR
18a modulates acquired tamoxifen resistance and the relevant mechanisms in
estrogen receptor (ER) positive cancer cells. METHODS: qRT-PCR was performed to
detect UCA1 and miR-18a expression in breast cancer cells. Dual luciferase assay
was performed to detect the binding between miR-18a and UCA1 3'UTR. Tamoxifen
sensitive MCF-7 cells were transfected with UCA1 expression vector or miR-18a
inhibitors. Tamoxifen resistant LCC9 and BT474 cells were transfected with UCA1
siRNA or miR-18a mimics. CCK-8 assay was performed to detect cell viability. Soft
agar assay was performed to assess cell colony formation. Flow cytometric
analysis was performed to check cell cycle distribution. RESULTS: UCA1 was
significantly upregulated in tamoxifen resistant LCC2, LCC9, and BT474 cells than
in tamoxifen sensitive MCF-7 cells. UCA1 expression was significantly upregulated
in MCF-7 cells after treatment with 0.1 MUmol/L tamoxifen. UCA1 overexpression
enhanced cell viability of MCF-7 cells after tamoxifen treatment, while UCA1
siRNA significantly suppressed viability of LCC9 and BT474 cells after tamoxifen
treatment. In MCF-7 cells, compared with vector control+tamoxifen group, the
average cell colony number and colony size of the UCA1+tamoxifen group was 19.0%
more and 29.0% larger respectively, while the proportions of the cells in G1
phase and in S phase were 7.3% lower and 6.7% higher respectively. In BT474
cells, compared with siRNA control+tamoxifen group, the average cell colony
number and colony size of the si-UCA1+tamoxifen group were 54.0% less and 42.0%
smaller respectively, while the proportions of the cells in G1 phase and in S
phase were 9.0% higher and 6.2% lower respectively. UCA1 directly interacted with
miR-18a and reduced its expression in ER positive breast cancer cells. Knockdown
of miR-18a increased viability of MCF-7 cells after tamoxifen treatment, while
miR-18a overexpression significantly reduced viability of BT474 cells after
tamoxifen treatment. In MCF-7 cells, compared with miRNA inhibitor
control+tamoxifen group, the average cell colony number and colony size of the
miR-18a inhibitor+tamoxifen group were 15.0% more and 33.0% larger respectively,
while the proportions of the cells in G1 phase and in S phase were 8.8% lower and
5.3% higher respectively. In BT474 cells, compared with miRNA control+tamoxifen
group, the average cell colony number and colony size of the miR-18a
mimics+tamoxifen group were 47.0% less and 25.0% smaller respectively, while the
proportions of the cells in G1 phase and in S phase were 13.3% higher and 7.9%
lower respectively. CONCLUSION: UCA1 can increase tamoxifen resistance of ER
positive breast cancer cells via competitively inhibiting of miR-18a.
PMID- 28416842
TI - [Drainage characteristic of the brain interstitial fluid detected by using
fluorescence and magnetic tracer method].
AB - OBJECTIVE: Compare the results of molecular diffusion and mass flow in the
interstitial space(ISS) displayed by using optical and magnetic probes and study
partitioned drainage of the brain interstitial fluid (ISF). METHODS: In the
study, 36 male SD rats were randomly divided into fluorescent inspection group
(18), magnetic tracer group (18). Then they were divided equally into caudate
nucleus (Cn), thalamus (T) and substantia nigra (Sn) subgroup, 6 rats in each
subgroup. Referencing the brain stereotaxic atlas, the coronal globus pallidus as
center level, Cn, T or Sn were acted as puncture positioning target. A 10 MUL
microsyringe was stereotaxically positioned and the lucifer yellow (LY) solution
of 2 MUL 10 mmol/L was infused into centric position. The coronary slices undergo
cardiac perfusion and fix respectively in time point Cn 3 h, T 2 h and Sn 1 h.
The rat brain was placed in rat stainless steel brain matrices and cut backward
along visual intersection. The injection point of coronal slice as the center
level, take 3 slices in front of the center level and 2 slices behind of it. 1 mm
for each slice and 6 slices in total. Then slices were detected by laser scanning
confocal microscope (LSCM). Simultaneous, in the same coordinate brain regions of
another three groups, a gadolinium-diethylene triamine pentaacetic acidm (Gd
DTPA) solution of 2 MUL 10 mmol/L was infused into different injection and
detected by MRI tracer-based method. Then the Radiant can be used to measure
distribution area of Gd-DTPA. RESULTS: LY and Gd-DTPA have different distribution
regions in Cn, T and Sn. After LY and Gd-DTPA were introduced into the Cn
subgroup 3 h, compare the 1 to 6 levels distribution area of LY and Gd-DTPA as
follows: (10.95+/-4.27) mm2 vs. (8.33+/-2.25) mm2, (18.16+/-4.74) mm2 vs.
(16.42+/-2.88) mm2, (24.57+/-3.65) mm2 vs. (20.75+/-2.29) mm2, (34.81+/-3.32) mm2
vs. (28.88+/-1.51) mm2, (30.53+/-3.12) mm2 vs. (20.92+/-2.75) mm2, (12.15+/-4.92)
mm2 vs. (10.00+/-1.89) mm2. The statistical analysis of every level was made by T
test, and the difference of the distribution area between the two tracers were
not statistically significant (t=0.940, P=0.400; t=0.546, P=0.614; t=1.534,
P=0.200; t=2.809, P=0.480; t=2.693, P=0.055; t=0.707, P=0.518); After LY and Gd
DTPA were introduced into the T subgroup 2 h, compare the 1-6 levels distribution
area of LY and Gd-DTPA as follows: (5.56+/-4.61) mm2 vs. (3.33+/-2.25) mm2,
(16.21+/-3.36) mm2 vs. (11.42+/-2.88) mm2, (19.00+/-5.21) mm2 vs. (15.75+/-2.29)
mm2, (25.32+/-5.49) mm2 vs. (22.33+/-3.25) mm2, (17.34+/-5.31) mm2 vs. (15.92+/
2.75) mm2, (7.67+/-6.19) mm2 vs. (5.00+/-1.89) mm2. The statistical analysis of
every level was made by T test, and the difference of the distribution area
between the two tracers were not statistically significant (t=0.753, P=0.493;
t=1.875, P=0.134; t=0.990, P=0.378; t=0.810, P=0.464; t=0.413, P=0.701; t=0.716,
P=0.514); After LY and Gd-DTPA were introduced into the Sn subgroup 1 h, compare
the 1-6 levels distribution area of LY and Gd-DTPA as follows: (6.78+/-4.56) mm2
vs. (4.75+/-2.00) mm2, (12.65+/-5.04) mm2 vs. (10.44+/-1.13) mm2, (19.51+/-6.54)
mm2 vs. (17.55+/-0.30) mm2, (28.72+/-5.45) mm2 vs. (24.48+/-1.32) mm2, (21.34+/
4.42) mm2 vs. (17.72+/-0.25) mm2, (13.00+/-5.46) mm2 vs. (12.00+/-2.88) mm2. The
statistical analysis of every level was made by T test and the difference of the
distribution area between the two tracers were not statistically significant
(t=0.705, P=0.519; t=0.743, P=0.499; t=0.517, P=0.656; t=1.310, P=0.260; t=1.416,
P=0.292; t=0.281, P=0.793), but the distribution area of LY is slightly more than
Gd-DTPA. CONCLUSION: LSCM imaging technology confirmed partitioned drainage of
the brain ISF found by MRI tracer-based method and provided technology and method
validation for MRI tracer-based method. LSCM imaging technology with higher
contrast and resolution, therefore more sophisticated partitioned drainage of the
brain interstitial fluid were got.
PMID- 28416843
TI - [Influences of repeated propofol anesthesia on hippocampal apoptosis and long
term learning and memory abilities of neonatal rats].
AB - OBJECTIVE: To investigate the influences of repeated propofol anesthesia on the
hippocampal apoptosis and the long-term learning and memory abilities of neonatal
rats. METHODS: In the study, 45 male Sprague-Dawley rats, aged 7 days, were
randomly divided into 3 group (n=15 each): control group (C group) that received
intralipid 7.5 mL/kg intraperitioneal (IP) once a day*7 days; group propofol 1
(P1) that received propofol 75 mg/kg IP once a day*7 days; group propofol 2 (P2)
that received intralipid 7.5 mL/kg IP once a day*6 days+propofol 75 mg/kg IP on
the 7th day. In each group, 5 animals were chosen and arterial blood samples were
obtained immediately after the animals were fully awake for blood gas analysis.
Learning and memory abilities were assessed using Morris water maze when the
other rats were 4 weeks old. The animals were decapitated after the tests. The
hippocampi were isolated for detection of neuron-specific nucleoprotein (NeuN)
expression by immunohistochemistry method and the expression of caspase-3 using
the Western blot. RESULTS: There was no significant difference in the indexes of
blood gas analysis among the 3 groups. Morris water maze test: compared with
group C, the escape latency and the length of searching on the 5th day were
significantly prolonged, and the searching time in target quadrant and platform
crossing on the 6th day were significantly decreased in group P1 (P<0.05) but not
in group P2. Compared with group C, NeuN-positive neurons were decreased, and the
expression of caspase-3 was increased in the rats of group P1 (P<0.05) but not in
group P2. CONCLUSION: Repeated propofol anesthesia may destroy long-term learning
and memory abilities by inducing apoptosis of hippocampal neurons in neonatal
rats, while single dose of propofol has no obvious effect on the hippocampal
apoptosis and long-term learning and memory of neonatal rats.
PMID- 28416844
TI - Clinical characteristics of neurogenic dysphagia in adult patients with Chiari
malformation type I.
AB - OBJECTIVE: To investigate changes of swallowing function and associated symptoms
in Chiari malformation typeI (CMI) patients with and without dysphagia by the
analysis of their clinical and high-resolution manometry (HRM) parameters.
METHODS: A total of 42 patients diagnosed with symptomatic CMI without
atlantoaxial dislocations which were confirmed by clinical manifestations and
magnetic resonance imaging (MRI) findings between January 2010 and July 2015 at
Peking University Third Hospital were included in this study. Twenty patients had
a history of various dysphagia symptoms, or reported symptoms of choking,
coughing after eating or drinking, while the other 22 patients denied symptoms of
dysphagia. The data collected from the medical records of these patients included
the patient's age, sex, date of diagnosis, duration of illness, symptoms, results
of MRI and HRM, and date of surgery. RESULTS: (1) Dysphagia group had 14 female
patients, and no-dysphagia group had 8 female patients. Dysphagia usually
occurred in female patients, and in addition to dysphagia, we recorded other
symptoms and signs in the CMI patients, including numbness, hypoesthesia, limb
weakness, neck pain, muscle atrophy, ataxia, hoarseness, symptoms caused by
posterior cranial nerve damage, pharyngeal reflex, uvula deviation, and pyramidal
signs. A higher percentage of the CMI patients with dysphagia (15/20) had
symptoms of posterior cranial nerve damage compared with the control group (5/22;
P=0.01). (2)HRM showed a significant difference in upper esophageal sphincter
(UES) relax ratio measurement (75.3% vs. 63.1%, P=0.023) and UES proximal margin
(17.2 cm vs. 15.7 cm, P=0.005) between the two groups. (3) The percentage of
syringomyelia affecting the bulbar or upper cervical region on MRI was
significantly higher in the dysphagia group (17/20 vs. 7/22, P=0.001).
CONCLUSION: CMI was usually accompanied by symptoms caused by posterior cranial
nerve damage, ataxia, and positive pyramidal signs. Location of the syringomyelia
affecting specifically the bulbar or upper cervical region was associated with
dysphagia in CMI patients. These findings suggest that the mechanism of dysphagia
in CMI may be due to a dysfunction in the neurological pathway of pharyngeal
muscle movement. Dysphagia etiology work-up should include CMI in the
differential diagnosis.
PMID- 28416845
TI - [Anesthetic choice for patients undergoing cesarean section complicated with
placenta implantation].
AB - OBJECTIVE: To investigate the anesthetic choice for patients undergoing cesarean
section complicated with placenta implantation. METHODS: A retrospective case
review of the patients with placenta implantation between 2008 and 2013 at Peking
University Third Hospital was conducted in the International Classification of
Diseases (ICD)-9 codes, excluding natural birth and not first diagnosed in our
hospital, a total of 96 cases were incorporated into this study. According to the
degree of implantation, they were divided into three groups: accreta group,
increta group and percreta group. We analyzed the time from the start of surgery
to baby delivery and the anesthetic technique. RESULTS: The accreta group
included 49 cases, the increta group 33 cases, and the percreta group 14 cases.
The average time from the start of surgery to fetus delivery in the three groups
were (6.7+/-3.0) min, (7.2+/-4.6) min, and (11.9+/-4.9) min, and the percreta
group was significantly different from the accreta group and the increta group
(P<0.05). There were significant differences among the three groups in anesthetic
choices (P<0.001): in the accreta group, 45 cases (91.8%) underwent spinal
anesthesia, 2 cases (4.1%) underwent general anesthesia, and 2 cases (4.1%) were
converted to general anesthesia after spinal anesthesia during the operation; in
the increta group, 22 cases (66.7%) underwent spinal anesthesia, 4 cases (12.1%)
underwent general anesthesia, and 7 cases(21.2%) were converted to general
anesthesia after spinal anesthesia; in the percreta group, 2 cases (14.3%)
underwent spinal anesthesia, 2 cases (14.3%) underwent general anesthesia, and 10
cases (71.4%) were converted to general anesthesia after spinal anesthesia.
CONCLUSION: Spinal anesthesia can be used as the first choice of cesarean section
complicated with placenta implantation and general anesthesia should be
considered in placenta percreta.
PMID- 28416846
TI - [Influence of the Arg-Gly-Asp-Ser sequence on the biological effects of bioactive
glass on human dental pulp cells].
AB - OBJECTIVE: Positive effects of bioactive glass (BG) on proliferation,
mineralization, and differentiation of human dental pulp cells (hDPCs) was
already verified in various former studies. The Arg-Gly-Asp-Ser sequence (RGDS)
was confirmed of affecting cell adhesion. Before further investigation, the
objective of this study is to investigate whether RGDS can affect the effects of
BG on the adhesion, proliferation and mineralization of hDPCs. METHODS: hDPCs
were harvested from third molars of 18-25-year-old individuals after informed
consent. Enzyme digestion technique was used. The 4th to 6th generation of hDPCs
were used for all experiments. The cells of the experimental groups were cultured
in Dulbecco minimum essential medium (DMEM) containing ionic dissolution products
of BG and RGDS of several concentrations (12.5 mg/L, 25.0 mg/L, 50.0 mg/L, 100.0
mg/L, 200.0 mg/L). DMEM containing ionic dissolution products of BG without RGDS
was used for cell culture as control group. Cell adhesion was tested 4 h after
cell seeding by MTT assay. Cell proliferation was examined at 1, 3, 5, 7, and 9 d
after cell seeding by MTT assay. Cell mineralization was investigated on days 14
and 28 by alizarin red staining. After being stained and dried, mineralized
nodules were dissolved by cetylpyridinium chloride (CPC) for semi-quantitative
test. Results were statistically analyzed by one way ANOVA, SPSS (version 19.0)
and P<0.05 was considered to be significant. RESULTS: Cell adhesion in BG group
showed no difference from that in DMEM group. Compared with BG group, hDPCs in
BG+RGDS groups suggested weaker cell adhesion.When the concentration of RGDS
increased, the adhered cell number decreased. hDPCs cultured with BG and RGDS
showed lower proliferation activity in the early stage, while no significant
difference was observed after 3 d. BG group promoted the mineralization of hDPCs
compared with positive control group, negative control group and RGDS group. No
significant difference was observed between BG+RGDS group and BG group or between
RGDS group and positive control group. CONCLUSION: BG promotes proliferation and
mineralization without affecting cell adhesion of hDPCs. Unbounded RGDS inhibits
cell adhesion, but has no influence on the positive effects of BG on the
proliferation and mineralization of hDPCs.
PMID- 28416847
TI - [Effects of bioactive glass and extracted dentin proteins on human dental pulp
cells].
AB - OBJECTIVE: To investigate the proliferation, odontogenic differentiation and
mineralization of human dental pulp cells (HDPCs) on bioactive glass(BG) and
extracted dentin proteins(EDP). METHODS: Primary HDPCs were isolated from third
molars by enzyme digestion and were cultured in Dulbecco's minimum essential
medium (DMEM). Then the 4th generation of HDPCs was cultured with DMEM, which
contained BG-EDP, BG, and EDP, respectively. Meanwhile HDPCs were cultured in
DMEM as control group. Proliferation of HDPCs was evaluated by 3-(4,5-dimethyl-2
thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) colorimetric assay.
Odontogenic differentiation was determined by alkaline phosphatase (ALP) activity
assay and real-time PCR. Mineralization was investigated by Alizarin red staining
and cetylpyridinium chloride (CPC) assay. RESULTS: The proliferation of HDPCs was
increased significantly in BG-EDP group on 3,7,and 9 d (optical density value:
1.36+/-0.06, 2.52+/-0.20, 2.72+/-0.29) compared with BG (optical density value:
1.20+/-0.26, 2.33+/-0.26, 2.50+/-0.30), EDP(optical density value: 1.13+/-0.15,
2.10+/-0.13, 2.38+/-0.22) and control group (optical density value: 0.84+/-0.17,
1.84+/-0.18, 1.95+/-0.19), P<0.05. After 7 days, ALP activity of BG-EDP group had
no statistical difference compared with EDP group and control group; the
expression of odontogenic differentiation genes (DSPP, DMP-1) showed no
difference among all the groups(P>0.05). After 14 days, ALP activity of BG-EDP
group (56.67+/-1.83) was significantly upregulated compared with EDP group
(41.98+/-9.71) and control group (30.82+/-6.70), P<0.05, but had no statistical
difference compared with BG group (56.29+/-6.20), P>0.05; DSPP gene expression
was upregulated significantly in BG-EDP group (5.79+/-1.94) compared with the
other groups (P<0.05); DMP-1 gene expression of BG-EDP group (3.87+/-1.87)
increased but had no statistical difference compared with the other groups
(P>0.05). The alizarin red staining showed more mineral nodules in BG-EDP group,
the cetylpyridinium chloride semi-quantification presented higher calcification
in BG-EDP group (0.27+/-0.01) compared with the other groups (P<0.05).
CONCLUSION: Compared with either BG or EDP, BG-EDP significantly promotes the
proliferation, odontogenic differentiation and mineralization of HDPCs.
PMID- 28416848
TI - [Effect of low-level laser irradiation on proliferation and osteogenic
differentiation of human adipose-derived stromal cells].
AB - OBJECTIVE: To examine the in vitro effects of low-level laser irradiation (LLLI)
on proliferation and differentiation of human adipose-derived stromal cells
(hASCs). METHODS: Cultured cells were exposed to different doses of LLLI with a
semiconductor diode laser (980 nm; 100 mW-12 W power output). The effects of
laser on proliferation were assessed daily up to seven days of culture in cells
irradiated for four consecutive days with laser doses of 2, 4, 6 or 8 J/cm2, the
cells without irradiation were used as controls. Half of the cells were changed
to osteogenic medium (OM) when they had grown to 70% confluence. The hASCs both
with and without osteogenic supplements were divided into three groups, and each
group was irradiated at doses of 0, 2 and 4 J/cm2. In order to examine the in
vitro effects of LLLI on osteogenic differentiation of hASCs, the alkaline
phosphatase activity was assessed on day 7, and alizarin red staining (AR-S) and
quantitative detection were assessed on days 14 and 21. The expression of
osteoblast master genes (ALP and Runx2) were tested on days 7 and 14. RESULTS:
The proliferation medium(PM)+LLLI4 J/cm2 group had the highest multiplication
rate. In the groups with osteogenic supplements, LLLI increased alkaline
phosphatase activity and mineralized nodule formation, and stimulated the
expression of ALP and Runx2. Furthermore, the effect became more obvious at high
dose. CONCLUSION: Our data demonstrated that hASCs proliferation and osteogenic
differentiation were enhanced by LLLI. With the increase of laser dose, the
effect of LLLI would be enhanced at first, and then be decreased after reaching a
peak.
PMID- 28416849
TI - [Effect of mechanical self-cleaning of tongue coating on malodor in halitosis
patients originating from tongue coating].
AB - OBJECTIVE: To evaluate the malodor level and to explore the effect of mechanical
self-cleaning of tongue coating in patients with halitosis originating from
tongue coating. METHODS: Ten patients with halitosis originating from tongue
coating were enrolled and divided into two groups randomly. The patients in test
group received instruction of mechanical cleaning of tongue coating while no such
instruction was given to control group. Organoleptic test (OLT) score, volatile
sulfide compounds (VSC) value, area of tongue coating (Ta), thickness of tongue
coating (Tt) and periodontal condition were recorded at baseline and were
repeated at the end of 1 week, 2 weeks, 4 weeks and 8 weeks later. The clinical
outcomes were compared at different time points between the groups. Also, changes
within the group were analyzed. RESULTS: As time went by, tongue coating area and
thickness tended to decrease in test group while the changes showed no
statistically difference (P>0.05). The organoleptic score in test group decreased
significantly (P<0.001). Changes of volatile sulfide compounds value within each
group had no statistically difference (P>0.05), though they showed a tendency to
decrease and fewer changes in control group were found. Compared with the
baseline, average probing depth and bleeding index (P<0.05) were significantly
lower in both the groups at the end of the test period, while no statistically
difference was observed between test group and control group (P>0.05). Plaque
index showed no difference at different time points in both the groups (P>0.05).
CONCLUSION: Mechanical self-cleaning of tongue coating did not influence plaque
index while it had tendency to reduce tongue coating area and thickness. Malodor
could be released after self-cleaning of tongue coating to a certain extent,
indicating necessity and importance of intervention role by dentists.
PMID- 28416850
TI - [Treatment of complicated intra-articular distal radius fractures with extended
flexor carpi radialis approach].
AB - OBJECTIVE: To discuss the effect of treatment of complicated intra-articular
distal radius fractures with extended flexor carpi radialis approach. METHODS: A
retrospective analysis of 38 cases with fresh complicated intra-articular distal
radius fractures treated by using extended flexor carpi radialis approach in our
hospital from October 2012 to March 2015, with 25 males and 13 females. The
average age was (52.76+/-8.62) years (32-64 years). The average time to surgery
was (5.42+/-1.91) d (3-10 d), with left wrist 17 cases and right wrist 21 cases.
All the patients were with C3 distal radius fractures according to Association
for the Study of Internal Fixation (AO/ASIF) classification. The follow-up was
conducted 1, 2, 3, 6, and 12 months after operation, including AP and lateral X
ray, wrist extension and flexion, radial deviation and ulnar deviation, forearm
pronation and supination, and grip strength. At the end of 6 and 12 months after
operation, all the patients were evaluated by using the modified Garland-Werley
score and patient rated wrist evaluation (PRWE). RESULTS: All the patients got
good bone union, and their follow-up time was more than 12 months. The average
follow-up time was (16.37+/-2.85) months (12-22 months). The score of modified
Garland-Werley evaluation 6 months postoperation was 5.37+/-2.82, excellent and
good rate was 84.21%, the score of modified Garland-Werley evaluation 12 months
postoperation was 5.03+/-2.60, excellent and good rate was 86.84%. The score of
PRWE 6 months postoperation was 15.82+/-8.38, the score of PRWE 12 months
postoperation was 12.17+/-7.58. CONCLUSION: The extended flexor carpi radialis
approach is effective for the treatment of complicated intra-articular distal
radius fractures and can avoid the complications of volar and dorsal combination
approach.
PMID- 28416851
TI - [One of the pitfalls in the surgical treatment of maisonneuve fractures: a case
report].
AB - There exist controversies in the surgical treatment of maisonneuve injury with
regard to reduction and fixation of syndesmosis and management of proximal
fibular fracture. It is very important for the orthopaedic surgeons to learn more
techniques and avoid pitfalls from clinical practice. We summarized the clinical
data of 1 failed case, a 20-year-old girl with big body weight who underwent a
primary surgery for the treatment of maisonneuve fracture with minimally invasive
reduction and fixation of ankle syndesmosis and posterior malleolus and open
reduction and internal fixation of medial malleolus, then a revision surgery for
the treatment of iatrogenic syndesmotic malreduction with open reduction and re
stabilization of ankle syndesmosis supplemented with open reduction and internal
fixation of proximal fibular facture. The malreduction of distal fibula was not
found until finishing the postoperative computed tomography (CT) scan 2 weeks
after the primary surgery, then the patient experienced an revision surgery
including removal of the screws installed primarily for fixation of ankle
syndesmosis, and open reduction and internal fixation of proximal fibular
fracture, and limited open reduction and re-stabilization of ankle syndesmosis.
Then the patient rehabilitated regularly under the direction of the surgeon who
performed these two operations, and the postoperative recovery was smooth, then
the hardwares for fixation of ankle syndesmosis and fracture of proximal fibula
and medial malleolus were removed at different postoperative time. The patient
experienced an excellent outcome at the end of the 3-year follow-up. The reasons
for the failure in this case might include the overemphasized minimally invasive
technique in the process of reduction, inaccurate assessment of intraoperative
fluoroscopy and postoperative radiographs, and inappropriate utilization of the
reduction clamp. Attention should be paid to the fact that an obliquely placed
clamp for closed reduction of diastasis of ankle syndesmosis could result in
syndesmotic malreduction. The worsened alignment of the fracture end of proximal
fibula observed by intraoperative fluoroscopy may alert surgeons to syndesmotic
malreduction. Partial exposure of syndesmosis and anatomical reduction and
fixation of proximal fibular fracture may be useful measurres to avoid
malreduction of ankle syndesmosis in the surgical treatment of maisonneuve injury
in some patient, especially the patient with critically destabilized ankle.
PMID- 28416852
TI - [First aid system for trauma: development and status].
AB - With the great progress of the economy, the level of industrialization has been
increasing year by year, which leads to an increase in accidental trauma
accidents. Chinese annual death of trauma is already more than 400 000, which
makes trauma the fifth most common cause of death, following malignant tumor,
heart, brain and respiratory diseases. Trauma is the leading cause of the death
of young adults. At the same time, trauma has become a serious social problem in
peace time. Trauma throws great treats on human health and life. As an important
part in the medical and social security system, the emergency of trauma system
occupies a very important position in the emergency medical service system. In
European countries as well as the United States and also many other developed
countries, trauma service system had a long history, and progressed to an
advanced stage. However, Chinese trauma service system started late and is still
developing. It has not turned into a complete and standardized system yet. This
review summarizes the histories and current situations of the development of
traumatic first aid system separately in European countries, the United States
and our country. Special attentions are paid to the effects of the pre- and in
hospital emergency care. We also further try to explore the Chinese trauma
emergency model that adapts to the situations of China and characteristics of
different regions of China. Our review also introduces the trauma service system
that suits the situations of China proposed by Professor Jiang Baoguo's team in
details, taking Chinese conditions into account, they conducted a thematic study
and made an expert consensus on pre-hospital emergency treatment of severe
trauma, providing a basic routine and guidance of severe trauma treatment for
those pre-hospital emergency physicians. They also advised to establish
independent trauma disciplines and trauma specialist training systems, and to
build the regional trauma care system as well as the standards for graded
treatment, thus establishing a multiple disciplinary team (MDT) of severe trauma.
In this way, we can reduce the mortality and disability risks of severe trauma,
improve the quality of patients' life, and save more lives.
PMID- 28416853
TI - Changes in soluble sugar metabolism in loquat fruit during different cold
storage.
AB - To investigate soluble sugar metabolism and its relationship to chilling injury
(CI), loquat fruits were stored at 0 and 5 degrees C for 5 weeks. CI symptoms
were monitored during storage, and soluble sugar content and related enzyme
activities were measured. Enzymes activities and substrate levels in the
ascorbate-glutathione (AsA-GSH) cycle were also determined. Fruit at 0 degrees C
had lower sucrose levels and higher levels of glucose and fructose than fruit
maintained at 5 degrees C, and also manifested less severe CI symptoms. Fruit at
0 degrees C also exhibited increased activities of acid invertase, neutral
invertase, sucrose phosphatesynthase and sucrose synthase. AsA-GSH cycle activity
at 0 degrees C was much higher than that at 5 degrees C. Glucose levels
correlated positively with levels of AsA and GSH and ascorbate peroxidase (APX)
activity. The increased glucose levels are sufficient to account for the chilling
tolerance of loquat fruit.
PMID- 28416854
TI - Physicochemical, functionality and storage stability of hog plum (Spondia
pinnata) juice powder produced by spray drying.
AB - Hog plum juice powder was obtained from its juice under optimized condition by
spray drying with juice: maltodextrin ratio at 2:1, 4:1 and 6:1 (v/w) basis. The
inlet temperature and feed rate were varied between 120 to 175 degrees C and 8
to 14 mL/min. The effect of variables i.e. maltodextrin level, temperature and
feed rate on the physicochemical properties and total phenolic content were
studied. Moisture content, hygroscopicity, bulk density, water activity and total
phenolic content of the powder were significantly affected by inlet temperature
and maltodextrin level. However feed rate showed no any significant effect on the
bulk density of the powder. An increase in inlet temperature and maltodextrin
level reduced the total phenolic content in the spray dried powder. Morphological
study showed that at high inlet temperature the spray dried powder were of smooth
surfaces however, at low inlet temperature majority of the particles were of
shrivelled surfaces. Spray dried hog plum juice powder made with 3.9:1 juice:
maltodextrin, processed at 171 degrees C inlet temperature and at 8 mL/min feed
rate had less hygroscopicity, water activity, moisture content and potent TPC
content. Storage temperature significantly affected the TPC and DPPH free radical
scavenging activity of the powder. Refrigeration temperature was found to be more
effective to reduce the losses of TPC and DPPH free radical scavenging activity
during storage. Colour acceptability of the refrigerated sample was comparatively
more than to the sample stored at room temperature.
PMID- 28416855
TI - Production and characterization of functional properties of protein hydrolysates
from egg shell membranes by lactic acid bacteria fermentation.
AB - This study aimed to ferment the chicken eggshell membrane (ESM) using the lactic
acid bacteria, Lactobacillus plantarum for preparation of functional and
bioactive protein hydrolysates. Cultivation at an initial pH of 8.0 for 36 h
resulted in maximum protein concentration (177.3 mg/g) and degree of hydrolysis
(25.1%) of the hydrolysates. Fermentation resulted in the production of
hydrolysates that demonstrated excellent solubility (90.7%), good foaming
capacity (36.7%) and emulsification activity (94.6 m2/g). Additionally, these
protein hydrolysates exhibited remarkable bioactive properties for instance
reducing power (2.53), protection from DPPH radical (70.5%) and angiotensin I
converting enzyme inhibition (49.3%). The fermented protein hydrolysates were
also found effective against various foodborne pathogens. The protein
hydrolysates obtained by fermentation of ESM can be potentially incorporated in
functional foods and nutraceuticals resulting in valorization of the ESM waste.
PMID- 28416856
TI - Microbial analysis of MAP pot-stewed duck wings under different conditions during
15 degrees C storage.
AB - This study was to investigate the changes of microbial community and counts of
MAP pot-stewed duck wing (PSDW) under different packaging films and spices ratio
during 15 degrees C storage, using the traditional bacterial cultivation and PCR
DGGE. Results of microbial counting showed that the shelf-life of PDSW during 15
degrees C storage for recommendation was within six days, and the packaging films
and spices ratio didn't affect the change of microbial numbers in PSDW during
storage. PCR-DGGE analysis revealed that Staphylococcus equorum, Weissella sp.,
Leuconostoc mesenteroides became the dominating bacteria of PSDW at the end of
storage, and high barrier cover film, general barrier base film and spice ratio
1:1, had a better inhibition effect on bacteria in PSDW products, which could be
used as the condition for PSDW storage. This study will help PSDW processing
enterprises visualize the biodiversity of PSDW during storage, and choose the
best condition for the subsequent processing.
PMID- 28416857
TI - Compositional variability of nutrients and phytochemicals in corn after
processing.
AB - The result of various process strategies on the nutrient and phytochemical
composition of corn samples were studied. Fresh and cooked baby corn, sweet corn,
dent corn and industrially processed and cooked popcorn, corn grits, corn flour
and corn flakes were analysed for the determination of proximate, minerals,
xanthophylls and phenolic acids content. This study revealed that the proximate
composition of popcorn is high compared to the other corn products analyzed while
the mineral composition of these maize products showed higher concentration of
magnesium, phosphorus, potassium and low concentration of calcium, manganese,
zinc, iron, copper, and sodium. Popcorn was high in iron, zinc, copper,
manganese, sodium, magnesium and phosphorus. The xanthophylls lutein and
zeaxanthin were predominant in the dent corn and the total polyphenolic content
was highest in dent corn while the phenolic acids distribution was variable in
different corn products. This study showed preparation and processing brought
significant reduction of xanthophylls and polyphenols.
PMID- 28416858
TI - Study on E. coli and Salmonella biofilms from fresh fruits and vegetables.
AB - Foodborne outbreaks associated with fresh fruits and vegetables are on the rise
worldwide. Biofilm formation is one of the important traits of pathogens making
them strongly attached to substrates as well as express virulence phenotypes.
Present study investigates the biofilm forming ability of E. coli and Salmonella
sp. isolated from fresh fruits and vegetables. A total of 53 strains, including
35 E. coli and 18 Salmonella sp. isolated from different fruit and vegetable
samples were taken into account for the study. Initial screening for biofilm
formation was done using Congo Red agar plate test. Results revealed that 22.8%
E. coli and 22.2% Salmonella sp. were potential biofilm formers. However, the MTP
(Micro-Titre Plate) assay suggested more isolates of both E. coli and Salmonella
sp. were moderate to strong biofilm producers. Agar plate diffusion assay with
Agrobacterium tumefaciens NTL-4 showed the production of quorum signaling
molecules (AHLs) by three isolates of E. coli and one Salmonella sp. Two E. coli
isolates showed a significant amount of EPS production indicating higher biofilm
forming potential. The Presence of LUX R homologue gene (sdiA) in two of the
Salmonella isolates were confirmed by PCR which demonstrated their potential
pathogenicity. Results of the work underline the biofilm forming and potentially
virulent capacities of isolates from the surface of fruits and vegetables.
PMID- 28416859
TI - Effect of catechin and its derivatives on inhibition of polyphenoloxidase and
melanosis of Pacific white shrimp.
AB - This study aimed to investigate the effect of tea catechin (C) and 4 of its
derivatives on the Pacific white shrimp PPO inhibition and melanosis during
refrigerated storage. Epigallocatechin gallate (EGCG) exhibited the highest
inhibition towards PPO, followed by C. Inhibitory activity of all compounds
tested was in a dose dependent manner (0.1-2.0 mM). Based on activity staining,
EGCG most effectively inhibited PPO. For inhibition kinetic studies, C and
epicatechin (EC) showed uncompetitive type, whereas epicatechin gallate (ECG),
epigallocatechin (EGC) and EGCG exhibited mixed type inhibition. When whole
shrimps were treated with EGCG solution at various concentrations (0.25-0.75%),
those treated with 0.5 or 0.75% EGCG had lower melanosis scores throughout
storage for 10 days at 4 degrees C, compared with the control and the 1.25%
sodium metabisulfite treated samples (P < 0.05). Therefore, EGCG could be used as
a potential inhibitor for melanosis in raw Pacific white shrimp during
refrigerated storage.
PMID- 28416860
TI - Characterization of phenolic profile and antioxidant capacity of different fruit
part from lemon (Citrus limon Burm.) cultivars.
AB - Phenolic composition and antioxidant capacity of different fruit part including
peel, pulp, juice, whole fruit and seed from five lemon cultivars (Feiminailao,
Cuningmeng Limeng, Pangdelusaningmeng, Beijingningmeng) were investigated.
Caffeic acid (9.31-741.4 MUg/g FW) and chlorogenic acid (2.7-527.5 MUg/g FW) were
the dominant phenolic acid in fruit tested, Pangdelusaningmeng (PD) and Limeng
peels with the highest contents, respectively. Hesperidin was the predominant
flavanone (10.27-3315 MUg/g FW), Cuningmeng (CN) peels with the highest level. PD
peels had rich rutin, CN seeds had rich eriocitrin. Nobiletin was the main
polymethoxylated flavonoids identified, PD with the highest level. CN peels
contained rich tangeretin. Overall, peels and whole fruit had significantly
higher level of phenolics than other fruit parts, and seeds were good source of
flavonoids. PD and CN not only contained higher level of phenolic, but also
presented higher antioxidant capacity than other cultivars tested, and are of
great value for human nutrition.
PMID- 28416861
TI - Application of genetic algorithm to optimize extrusion condition for soy-based
meat analogue texturization.
AB - The aim of this study was to find the optimum extrusion process conditions for
texturized soybean meal as a meat analogue for food formulations using genetic
algorithm. The defatted soybean meal was replaced with whole soybean meal at 10%
and extruded in the temperature range of 150-200 degrees C, screw speed of 270
300 rpm and 20-25% feed moisture content based on the Box-Behnken design. The
barrel temperature effect was markedly greater than those of the feed moisture
content and screw speed on the product functional properties and appearance.
Higher temperatures led to a higher rehydration capacity, water and oil
absorption capacity, however, it had a negative effect on the product brightness.
It was found that the extrusion at lower moisture content improved soy protein
functionality. Genetic algorithm technique was applied to find the best process
conditions. The optimized process conditions were found to be the temperature of
198.8 degrees C, screw speed of 291 rpm and feed moisture content of 20.2%.
Overall, the whole soybean treatment was applicable to overcome the oil
separation issue during extrusion and the process was optimized to produce
texturized soy protein with the maximum attainable functionality.
PMID- 28416862
TI - Biscuits fortified with micro-encapsulated shrimp oil: characteristics and
storage stability.
AB - Characteristics and storage stability of biscuits fortified with micro
encapsulated shrimp oil (MSO) were determined. The addition of MSO increased
spread ratio, whilst decreased the thickness of biscuit. The highest hardness of
biscuit was obtained with addition of 9 or 12% MSO. Biscuit surface showed higher
redness and yellowness when MSO was incorporated (p < 0.05). The addition of MSO
up to 6% had no adverse effect on biscuit quality and acceptability. When
biscuits added with 6% MSO were stored under different illumination conditions
(light and dark), lipid oxidation in all samples increased throughout the storage
of 12 days. Light accelerated lipid oxidation of biscuits as evidenced by the
increases in both peroxide values and abundance of volatile compounds. No marked
change in EPA, DHA and astaxanthin contents were noticeable in biscuit fortified
with MSO after 12 days of storage. Therefore, the biscuit could be fortified with
MSO up to 6% and must be stored in dark to assure its oxidative stability.
PMID- 28416863
TI - Protective effects of tetrahydrocurcumin (THC) on fibroblast and melanoma cell
lines in vitro: it's implication for wound healing.
AB - The aim of this study was to investigate the role of tetrahydrocurcumin (THC)
against various skin health parameters using in vitro human foreskin fibroblast
and melanoma cell lines (i.e. HFF-1 and B16-F10). The study was assessed using
cell viability by MTT assay, identification of extracellular matrix component in
HFF-1 cell line (i.e. collagen, elastin and hyaluronic acid), melanin synthesis
in B16-F10 cells, cell viability against UVB-induced stress in HFF-1 cells, and
in vitro wound healing by the scratch assay. THC was found to be safe and
nontoxic up to the concentration of 10 ug/mL with improved level of collagen
(37.90%), elastin (90.1%), and hyaluronic acid (74.19%) at 1 ug/mL. Besides,
melanin was significantly inhibition by 78.5% at the lowest THC concentration of
0.1 ug/mL. UVB-protection rate was significantly improved by 61.2% and improved
cell viability by THC in HFF-1 cells, which indicated protection from photoaging.
In addition, THC showed significant wound healing activity (78.51%) and greater
migration of fibroblast in HFF-1 cells at different time period. It can be
concluded from the study that THC can protect the skin matrix with improved
extracellular component synthesis and would healing via collagen synthesis in the
skin, which improved the skin elasticity and tightness. Overall, it might be
suggested that THC can be used as a safe skin whitening agent, wounds management,
cosmetic applications, and treating various skin-related disorders.
PMID- 28416864
TI - Synthesis of structured lipids containing behenic acid from fully hydrogenated
Crambe abyssinica oil by enzymatic interesterification.
AB - Low-calorie structured lipids (SLs) rich in behenic and oleic acids were produced
by enzymatic (EI) and chemical interesterification (CI) of high oleic sunflower
oil and fully hydrogenated Crambe abyssinica oil in proportions of 60:40, 50:50,
40:60 and 30:70 (w/w), respectively. The immobilized lipase from Thermomyces
lanuginosus (Lipozyme TL IM) was used for 3 h at 70 degrees C at a dosage of 7%
(w/w) free of organic solvents. The original blend (BE) and the reaction products
were evaluated for their fatty acid (FA) and triacylglycerols (TAG) compositions,
solid fat contents, thermal analysis, regiospecific distribution of the FA,
microstructure and polymorphism. The tendency was towards a reduction in the C52,
C54, C60, C62 and C64 TAG contents and an increase in the C56, C58 e C66 TAG
contents, therefore the solid fat content was reduced. There was lower acyl
migration at the sn-2 position of the TAGs in EI as compared to CI in all the
blends ratios. Needle-like crystals were predominant in the IE while large
symmetrical spherulites were observed in the BE. Reduction in the mean crystal
diameter was observed in all the blends, in addition to modifications of the
crystal morphology. X-ray diffraction analysis showed a predominance of the beta'
form crystals in both the IE and CI. The SLs were produced for application in the
food industry as bakery/confectionery fats in the proportions of 60:40/50:50 and
as additive in the crystallization of lipids in the proportions of 40:60/30:70.
PMID- 28416865
TI - Folic acid content and antioxidant activity of different types of beers available
in Hungarian retail.
AB - In this study 40 Hungarian retail beers were evaluated for folic acid content,
antioxidant profile and physicochemical parameters. The physicochemical
parameters, folic acid content and antioxidant activity of alcohol-free beers
were the lowest. Folic acid content of beers aged with sour cherries showed high
values, more than 0.4 mg/l and an alcohol-free beer-based mixed drink made with
lemon juice contained more than 0.2 mg/l of folic acid. Dark beers and beers aged
with sour cherries had the highest antioxidant activity probably owing to their
high extract content, components released from the fruits and special malts.
These results highlight the possibility of achieving adequate folic acid and
relevant antioxidant intake without excessive alcohol and energy consumption by
selecting appropriate beer types.
PMID- 28416867
TI - Response surface optimization of low-fat ice cream production by using resistant
starch and maltodextrin as a fat replacing agent.
AB - In this research, maltodextrin (0, 1 and 2% w/w) and resistant starch (0, 1 and
2% w/w) were used in the formulation of low-fat ice cream (4% fat) and their
effects on the physicochemical and sensory properties were investigated. The
optimum levels of maltodextrin and resistant starch were determined by response
surface methodology. Increment of maltodextrin and resistant starch increased
acidity, viscosity, melting rate, time of dripping and overrun but decreased
melting rate of ice cream. Results showed that the incorporation of maltodextrin
and resistant starch at 0 and 2% w/w respectively, resulted into ice cream with
suitable viscosity, melting rate, first dripping time, overrun and acidity.
PMID- 28416866
TI - Rheology and microstructure of kefiran and whey protein mixed gels.
AB - The effect of kefiran on cold-set gelation of whey protein isolate (WPI) at 25
degrees C was studied using rheological measurements and environmental scanning
electron microscopy (ESEM). The gelation of samples was induced by the addition
of glucono-delta-lactone to the dispersions. WPI concentration was maintained at
8% (w/v) and the concentration of kefiran varied from 0 to 0.08% (w/v). According
to rheological measurements, the addition of kefiran into WPI dispersions
resulted in a significant increase in the gel strength, the yield stress, and the
shear stress values at the flowing point. The gelling point and gelation pH of
samples decreased significantly with an increase in kefiran concentration. ESEM
micrographs showed that the presence of kefiran played an important role in the
microstructure formation of gels. The microstructure of kefiran-WPI mixed gels
was more compact and dense, compared to the WPI gel. Depletion interactions
between kefiran and whey protein aggregates can be regarded as the chief factor
which was responsible for these effects. The present work demonstrated that
rheological and microstructural properties of acid-induced whey protein gels were
improved by the addition of kefiran.
PMID- 28416868
TI - A synergistic effect of Cremophor and beta glucosylceramide to exert liver and
sugar protection.
AB - Many commonly used drugs carry the potential to induce hepatotoxicity, and a
large number of foods and beverages induce an increase in blood sugar levels. A
change in lifestyle by omitting these compounds is not applicable in many
circumstances. beta-Glucosylceramide (GC) is a naturally occurring
glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL)
is a synthetic, nonionic surfactant that is used as a vehicle for the
administration of water-insoluble compounds. The aim of the present study was to
determine the synergistic effect of oral administration of the combination of GC
and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched
compounds. Four groups of mice, treated with PBS, GC, CrEL, or GCC were studied
in the concanavalin A immune-mediated hepatitis model, in the acetaminophen
(APAP) toxicity model, and as additives to two types of sugar-enriched soda
drinks. Both GC and CrEL exerted hepatoprotective effects in the ConA hepatitis
and APAP toxicity models. Moreover, in both models, GCC exerted a synergistic
effect in ameliorating liver damage as manifested by a significant decrease in
the ALT serum levels. When added to two types of sugar-enriched sodas, GCC
exerted a synergistic effect in ameliorating the increase in blood sugar levels.
GCC exerts synergistic hepatoprotective and glucose-protective effects in models
of liver damage and increased serum glucose. GCC can provide liver and sugar
protection when co-administered with hepatotoxic drugs or sugar-enriched drinks.
PMID- 28416869
TI - Effects of ethyl oleate and microwave blanching on drying kinetics of bitter
gourd.
AB - In the present study effects of pre-treatments such as blanching with hot water
and microwave, ethyl oleate dipping, and combinations of these treatments on
drying characteristics of the bitter gourd (Momordica charantia L.) at various
temperature were studied. The overall drying time was reduced significantly in
the ethyl oleate treated and microwave blanched samples. The minimum diffusivity
(2.65 * 10-8 m2/s) was observed in control samples whereas the maximum
diffusivity (3.86 * 10-8 m2/s) was observed in ethyl oleate treated and microwave
blanched samples at 50 degrees C. Ethyl oleate treated and microwave blanched
samples dried at lowest temperature (50 degrees C) showed the lowermost
shrinkage ratio (46.04%). The rehydration ratio increased from 3.49 to 4.90 as
the temperature increased from 50 to 70 degrees C for control samples. Combined
pre-treatment of ethyl oleate and microwave blanching had resulted in most
acceptable drying characteristics and quality of bitter gourd. Drying of the
samples were mathematically modelled. The drying characteristics of bitter gourd
could be explained suitably by Page drying model.
PMID- 28416870
TI - Antagonistic activity of Thymus vulgaris extracts against Vibrio species isolated
from seafoods.
AB - This study examined the antibacterial activity of Thymus vulgaris on multiple
antibiotic resistant (MAR) Vibrio parahaemolyticus and Vibrio fluvialis isolated
from shrimps. The ethanol extract of T. vulgaris antibacterial properties was
assessed using the agar diffusion method. Survival of test organisms in shrimp
meat using different concentrations of T. vulgaris was done using standard
method. The quantitative and qualitative phytochemical tests of T. vulgaris
extract were determined. The ethanol extract had antimicrobial activities on the
test organisms showing 20.00 +/- 0.0 and 23.00 +/- 0.0 mm zone of inhibition on
V. parahaemolyticus and V. fluvialis respectively. T. vulgaris completely
decreased microbial load of V. parahaemolyticus and V. fluvialis in 150 and 60
min, respectively. The phytochemical screening for the ethanol extract reported
phenol, alkaloids, tannin, saponin, anthraquinone flavonoid and cardiac glycoside
as 51.76, 26.60, 6.76, 54.33, 30.35 89.65 and 18.23 mg/100 g, respectively. This
study reveals the antibacterial property of T. vulgaris on the MAR Vibrio
species.
PMID- 28416871
TI - Effect of water quality on the main components in Fuding white tea infusions.
AB - The aim of this study was to investigate the effect of water quality on the main
components in Fuding white tea infusions, including catechins, caffeine, theanine
and free amino acids. Pure, tap and spring water were tested, and water quality
was found to have a distinct effect on the main compounds extracted. Pure water,
which was weakly acidic and low in dissolved ions, achieved the highest catechin
content, whereas caffeine and theanine, and amino acids, were higher in infusions
made with spring and tap water, respectively. Sensory evaluation was performed to
evaluate infusion colour, taste and aroma, and sensory quality was similarly
influenced by water type, due primarily to differences in dissolved ions. Pure
water was more suitable for brewing white tea with superior colour, aroma and
taste.
PMID- 28416872
TI - Impact of light irradiation on black tea quality during withering.
AB - Black tea manufacture usually involves the processes of withering, cutting,
fermentation and drying. The aim of present study was to evaluate the effect of
the relationship between the quality and withering with different light sources
(ultraviolet, yellow, blue, purple, orange, red, cyan, green and white) an
quality attribute of tea. The results indicated that the yellow, orange and red
light withering significantly improved the aroma and taste, imparting the tea a
sweet flavor and a fresh and mellow taste. Tea treated with yellow light was
scored highest the sensory scores and showed the highest content in catechins,
theaflavins, amino acids and aroma components, followed by the orange and red
light treatments. The black tea withered with ultraviolet light showed a strong
astringency, probably resulting from low contents of theaflavins, amino acids and
soluble sugar. The green light irradiation remarkably damaged the aroma and taste
of the tea, leading to a strong greenish flavor and an astringent taste, probably
owing to the lowest contents of chemical compositions. No significant cumulative
effect was found in the hybrid light withering treatments. Therefore,
monochromatic yellow, orange and red lights were suggested for withering the
black tea to improve its overall quality.
PMID- 28416873
TI - Collagen extraction from mussel byssus: a new marine collagen source with
physicochemical properties of industrial interest.
AB - Mussel byssus is a by-product of mussel production and is a potential source of
collagen. The goal of this study was to extract collagen from the byssus of
Chilean mussel using an enzymatic method and characterize it. A pepsin-aided
extraction method was employed where first an enzymatic hydrolysis at two
pepsin/substrate ratios (1:50 or 4:50) and times (4 or 24 h) was done. Extraction
was conducted at 80 degrees C for 24 h, in a 0.5 N acetic acid solution. All
samples were analyzed for collagen content, amino acid profile, turbidity,
viscosity, solubility, denaturation temperature and surface tension. Hydrolysis
time had significant effect on collagen content, hydroxyproline content and
extraction yield. Hydrolysis with a pepsin/byssus ratio of 4:50 for 24 h gave the
better extraction performance with values of 69 mg/g protein, 1.8 mg/g protein
and 30%, for collagen content, hydroxyproline content and extraction yield,
respectively. No differences were found for the viscosity and surface tension of
collagen dispersions, suggesting that the enzymatic hydrolysis did not affect the
integrity of the collagen molecule. Denaturation temperature of freeze-dried
byssus collagen presented a high value (83-91 degrees C), making this kind of
collagen a very interesting material for encapsulation of bioactive molecules and
for biomedical applications.
PMID- 28416874
TI - Effect of microwave drying on quality kinetics of okra.
AB - The effects of microwave drying on quality attribute of okra were evaluated.
Microwave power values show significant effect on moisture diffusivity, color,
hardness and sensory attributes of dried okra. The total color change ([Formula:
see text]) increased whereas [Formula: see text], [Formula: see text] and
[Formula: see text] decreased with an increase in both power and time. The
kinetics of [Formula: see text] and [Formula: see text] were well expressed by
zero-order kinetic models, while [Formula: see text] and [Formula: see text]
followed first-order kinetic models. Hardness was expressed by a first-order
kinetic model. Sensory evaluation showed that okra dried at 800 W was most
attractive in terms of color, texture, flavor and overall liking. Microwave
drying at 800 W presented the shortest drying time with the least change in
hardness, but the most change in color. Thus, high-power microwave drying
potentially produces dried fruits and vegetables with minimum changes in
hardness.
PMID- 28416875
TI - Hawberry (Crataegus monogyna Jaqc.) extracts inhibit lipid oxidation and improve
consumer liking of ready-to-eat (RTE) pork patties.
AB - The objective of this work was to study the effectiveness of extracts from
hawberry (Crataegus monogyna Jacq.) to inhibit lipid oxidation and odor
deterioration during processing of ready-to-eat (RTE) pork patties subjected to
roasting (180 degrees C/16 min), chilling (10 days/+3 degrees C) and reheating
in microwave (600 mW/1 min). Acetone extracts of hawberry were chosen based on
their total phenolic content (1281.1 +/- 84.8 mg gallic acid equivalent (GAE)/100
g fruit) and in vitro antiradical activity (DPPH) (53.33 +/- 15.40 g equivalent
Trolox per g of fruits). Pork patties treated with increasing concentrations of
hawberry extract, 200 and 800 ppm GAE (T2 and T8, respectively) and a control
group (T0) of samples, were analyzed for TBARS, volatile carbonyls and odor
liking in a consumer test. Hawberry extracts significantly improved the oxidative
stability of cooked pork patties keeping TBARS and hexanal counts at basal levels
during the whole process. The addition of hawberry phenolic-rich extracts
significantly improved the degree of consumer satisfaction regarding the odor of
patties. In conclusion, the hawberry extract displayed potential usage as an
ingredient with antioxidant properties for the manufacture of high-quality RTE
meat products.
PMID- 28416876
TI - Comparison of rheological behaviors and nanostructure of bighead carp scales
gelatin modified by different modification methods.
AB - In this study, microbial transglutaminase (MTGase) and pectin were compared to
modify bighead carp (Hypophthalmichthys nobilis) scale gelatin. The functional
properties of modified fish scales gelatin (FSG) were largely improved, including
melting temperature and rheological behavior. While, modification methods
decreased the triple-helix content and destroyed the single left-hand helix chain
of modified FSG as investigated by X-ray diffraction. MTGase could induce the
denser and finer gels network, but had none significant effect on nanostructural
properties of fish gelatin. Pectin inserted itself into the fish gelatin gels
network and caused aggregations, forming crystalline peaks and various
nanostructures. In particular, compared with pectin modified FSG, MTGase produced
FSG with lower storage modulus and apparent viscosity, but higher gel points and
melting points.
PMID- 28416877
TI - Quality, antioxidant activity and composition of Indian black teas.
AB - A comparative study was undertaken to determine the difference in quality,
antioxidant activity, and mineral content of northern and southern Indian tea
varieties. The results showed that the antioxidant activity, theaflavin and
thearubigin content, color particle size and total soluble solids influence the
tea leaf and tea dust. Assam leaf showed higher values for all the physico
chemical properties followed by Darjeeling leaf. In addition, the mineral
composition of the tea infusion was also influenced. The preparation method,
including the amounts of tea and water used, infusion time was shown to be a
major determinant of the component concentrations of tea beverages as consumed.
An illustration of the variation introduced by these varieties of tea is provided
by comparing solids, caffeine, minerals and antioxidant activity of black teas
available locally.
PMID- 28416878
TI - Imitation of soymilk-cow's milk mixed enzyme modified cheese: their composition,
proteolysis, lipolysis and sensory properties.
AB - Combined use of soymilk-cow's milk is a novel approach in food industry and has
great potential to developed products with numerous health benefits. This study
aimed to develop the enzyme-modified cheeses (EMCs) using soymilk-cow's milk. The
curd was hydrolysed using combination of proteinases/peptidase to produce a range
of proteolysed products followed by lipolysis to create flavoured EMCs. Results
showed that enzymes led to an increase in amino acids (AA), free fatty acids
(FFA), complex volatiles, and improved sensory attributes. The EMCs showed higher
mean values of AA, FFA and volatile compounds when prepared using Flavourzyme(r)
in combination with Lipases AY30 and DF15. EMCs were less eggy, bitter, pungent,
more buttery, saltier, nutty, and had sweet sensory characteristics. Overall,
results demonstrated the potential of combined matrix to create a range of
flavoured EMCs for a wider range of consumers.
PMID- 28416879
TI - Supercritical CO2 extraction of candlenut oil: process optimization using Taguchi
orthogonal array and physicochemical properties of the oil.
AB - A series of experiments was conducted to determine optimum conditions for
supercritical carbon dioxide extraction of candlenut oil. A Taguchi experimental
design with L9 orthogonal array (four factors in three levels) was employed to
evaluate the effects of pressure of 25-35 MPa, temperature of 40-60 degrees C,
CO2 flow rate of 10-20 g/min and particle size of 0.3-0.8 mm on oil solubility.
The obtained results showed that increase in particle size, pressure and
temperature improved the oil solubility. The supercritical carbon dioxide
extraction at optimized parameters resulted in oil yield extraction of 61.4% at
solubility of 9.6 g oil/kg CO2. The obtained candlenut oil from supercritical
carbon dioxide extraction has better oil quality than oil which was extracted by
Soxhlet extraction using n-hexane. The oil contains high unsaturated oil
(linoleic acid and linolenic acid), which have many beneficial effects on human
health.
PMID- 28416880
TI - Frying of rice flour dough strands containing gum Arabic: texture, sensory
attributes and microstructure of products.
AB - The effects of rice flour (50-56%, w/w) and gum Arabic (0-5%, w/w) on the
physical, sensory and structural features of the fried dough strands were
investigated. Up to 25.8% reduction in oil was possible by the incorporation of
gum Arabic. The wide variations in failure force (13.8-25.3 N) and failure strain
(11.0-28.6%) indicated the formation of snacks varying in texture from a soft-to
bite brittle product to a hard-to-eat less brittle sample. The snacks possessed a
porous microstructure with air cells, pores and vacuoles; the cell walls were
more than 100 MUm in thickness. The textural parameters like failure force,
failure energy and failure stress behaved in a similar manner in the principal
component analysis biplot. High moisture content in the dough decreased the
sensory acceptance of the fried snacks. The high desirability index of 0.9 could
be achieved with a high level of rice flour (56%, w/w) while gum Arabic content
was between 3.50 and 3.75% (w/w).
PMID- 28416881
TI - Use of chitosan coating in increasing the shelf life of liquid smoked Nile
tilapia (Oreochromis niloticus) fillet.
AB - The aim of this research was to evaluate the efficiency of liquid smoking and
chitosan coating on the shelf life of Nile tilapia (Oreochromis niloticus)
fillets. Fillets without liquid smoked and chitosan coating (control), liquid
smoked fillets (LS), and liquid smoked and chitosan coated fillets (LSCh) were
stored at 4 +/- 1 degrees C for 30 days. The physicochemical (pH, moisture
content, water activity-aw, color, texture, total volatile bases nitrogen-TVB-N
and thiobarbituric acid reactive substances-TBARS) and microbiological analyses
(mesophilic and psychrotrophic counts) and the electrophoresis profile of samples
were carried out. Physicochemical parameters, such as TVB-N and TBARS, were
reduced in the tilapia fillets with liquid smoking. The presence of the coating
of chitosan was effective for the control of the microorganisms during storage.
This work showed that the addition of a chitosan coating in liquid-smoked fillets
further enhanced the effect of preservation.
PMID- 28416882
TI - Chemical composition, antiproliferative and antioxidant activity of differently
processed Ganoderma lucidum ethanol extracts.
AB - The content of phenolic compounds (TPC) and glucans, as well as the effectiveness
of antiproliferative and antioxidant activity of differently processed Ganoderma
lucidum ethanol extracts were determined and compared. The content of glucans
(total, alpha- and beta-) strongly depended on the extraction time and particle
size, but only interaction of these parameters influenced the TPC. Gallic acid,
quercetin, trans-cinnamic acid, kaempferol, hesperetin and naringenin were
detected in extracts by HPLC-DAD. The most abundant phenols were hesperetin
(1.875-3.222 ug/g) and naringenin (1.235-2.856 ug/g). The ethanol extracts
exhibited noteworthy antioxidant activity, but the significant amount of phenolic
compounds was strongly linked to polysaccharides, and hence reduced their
antioxidant capacity. The results of the antiproliferative activity in vitro
showed that the analyzed extracts were the most effective against HeLa cells.
Significant correlations were observed between the antiproliferative effect and
the TPC/glucan content of extracts.
PMID- 28416883
TI - Application of electrolysed oxidising water as a sanitiser to extend the shelf
life of seafood products: a review.
AB - Electrolysed oxidising water (E.O. water) is produced by electrolysis of sodium
chloride to yield primarily chlorine based oxidising products. At neutral pH this
results in hypochlorous acid in the un-protonated form which has the greatest
oxidising potential and ability to penetrate microbial cell walls to disrupt the
cell membranes. E.O. water has been shown to be an effective method to reduce
microbial contamination on food processing surfaces. The efficacy of E.O. water
against pathogenic bacteria such as Listeria monocytogenes, Escherichia coli and
Vibrio parahaemolyticus has also been extensively confirmed in growth studies of
bacteria in culture where the sanitising agent can have direct contact with the
bacteria. However it can only lower, but not eliminate, bacteria on processed
seafoods. More research is required to understand and optimise the impacts of
E.O. pre-treatment sanitation processes on subsequent microbial growth, shelf
life, sensory and safety outcomes for packaged seafood products.
PMID- 28416884
TI - Determination of soluble dietary fibre content of Okara treated with high
hydrostatic pressure and enzymes: a comparative evaluation of two methods (AOAC
and HPLC-ELSD).
AB - ABSTRACT: Okara is a promising by-product from soybean and a rich source of
dietary fibre, chiefly insoluble (IDF). To increase its solubility and
functionality, a treatment with high hydrostatic pressure (HHP) assisted by food
grade enzymes -Ultraflo(r) L or Viscozyme(r) L- has been performed. To monitor
the effectiveness, an analysis of dietary fibre, mainly the soluble fraction
(SDF), was accomplished by the AOAC enzymatic-gravimetric method with dialysis
followed by both, spectrophotometric methods and High Performance Liquid
Chromatography with Evaporative Light Scattering Detector (HPLC-ELSD) analysis of
the soluble fraction. A significant increase in SDF (~1.5-times) to the expense
of a decrease in IDF was shown and chromatograms revealed two peaks of 95 and 22
kDa. Thus, treated Okara possessed a more balanced and convenient ratio of
soluble to insoluble dietary fibre, which could have health benefits as
prebiotic. Inbuilt interferences of the official AOAC's method for dietary fibre
were confirmed and the direct HPLC-ELSD approach was about twice more sensitive
than spectrophotometric methods. Consequently, the direct HPLC-ELSD analysis of
the supernatant is proposed as a cheaper, faster and reliable method. Combined
HHP-treatments plus specific enzymes represent a promising alternative for the
valorisation and preservation of agrofood by-products. GRAPHICAL ABSTRACT:
PMID- 28416885
TI - Effect of chitosan treatment on strawberry allergen-related gene expression
during ripening stages.
AB - The effectiveness of a chitosan coating treatment on the allergen-related genes
expression of three strawberry cultivars (Fragaria * ananassa Duch., namely cvs.
"Sabrina", "Candonga" and "Jonica") harvested at three ripening stages was
evaluated. Fruits were treated with a 1% chitosan coating and stored at 20
degrees C for 48 h. Three genes, encoding Fra a1, Fra a3 and Fra a4 allergens,
were evaluated by real-time qPCR. The transcript levels of several genes showed
different patterns during ripening stages in strawberry cultivars but were up
regulated by chitosan treatment.
PMID- 28416886
TI - Optimization of reuterin production in cheese by Lactobacillus reuteri.
AB - Cheeses manufactured from pasteurized milk supplemented with glycerol and
reuterin-producing Lactobacillus reuteri INIA P572 as adjunct to the commercial
starter culture were analysed in order to optimize a biopreservation strategy.
The highest reuterin concentration determined by a colorimetric assay was
detected on day 1 in cheeses with 100-500 mM glycerol. The presence of reuterin
was confirmed by a direct detection technique as HPLC. Cheeses made with L.
reuteri and 200 or 500 mM glycerol showed a red tendency in color in comparison
with control. The results with purified reuterin suggested that the development
of slightly rosy colour in cheese was related to some compound
produced/overproduced when higher levels of glycerol were present in cheese, but
not due to reuterin. Application of L. reuteri INIA P572 as adjunct to the
commercial starter with 100 mM glycerol led to such a reuterin concentration in
cheese that could control undesirable microorganisms, avoiding the presence of
color-changing compounds.
PMID- 28416887
TI - A preliminary study of PCBs, PAHs, pesticides and trace metals contamination in
cold-pressed rapeseed oils from conventional and ecological cultivations.
AB - The purpose of this study was to investigate the levels of polycyclic aromatic
hydrocarbons [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, and
benzo(a)pyrene], polychlorinated biphenyls (6 marker and 12 dioxin-like),
pesticides (74 compounds) and heavy metals (Pb, Cd, As, Hg, Fe, Cu), in the cold
pressed rapeseed oils from conventional (RC) and ecological cultivations (RE).
Similar level of PAHs, PCBs and heavy metals was found in the investigated cold
pressed oils; moreover, no effect of rapeseeds cultivation practice on the level
of pesticide residues was found. Levels of PAHs, PCBs, and pesticides were within
EU legislation limits. Concentration of 4 PAHs oscillated between 3.13 and 6.15
MUg/kg, concentration of non-dioxin-like PCBs was within 2599.4-8380.8 pg/g
range, dioxin-like PCSs levels varied from 310.2 to 819.4 pg/g (0.307-0.780 pg
TEQ/g oil). Iron (Fe) and copper (Cu) were prevailing heavy metals found in the
studied oils (0.236-1.690 mg/kg range, 0.036-0.062 mg/kg range, respectively).
Measured lead (Pb) contents reached (RC1) or were nearly equal to the EU limit of
0.1 mg/kg (RE1 and RE2).
PMID- 28416888
TI - Tailoring Pore Size and Chemical Interior of near 1 nm Sized Pores in a
Nanoporous Polymer Based on a Discotic Liquid Crystal.
AB - A triazine based disc shaped molecule with two hydrolyzable units, imine and
ester groups, was polymerized via acyclic diene metathesis in the columnar
hexagonal (Colhex) LC phase. Fabrication of a cationic nanoporous polymer (pore
diameter ~1.3 nm) lined with ammonium groups at the pore surface was achieved by
hydrolysis of the imine linkage. Size selective aldehyde uptake by the cationic
porous polymer was demonstrated. The anilinium groups in the pores were converted
to azide as well as phenyl groups by further chemical treatment, leading to
porous polymers with neutral functional groups in the pores. The pores were
enlarged by further hydrolysis of the ester groups to create ~2.6 nm pores lined
with -COONa surface groups. The same pores could be obtained in a single step
without first hydrolyzing the imine linkage. XRD studies demonstrated that the
Colhex order of the monomer was preserved after polymerization as well as in both
the nanoporous polymers. The porous anionic polymer lined with -COOH groups was
further converted to the -COOLi, -COONa, -COOK, -COOCs, and -COONH4 salts. The
porous polymer lined with -COONa groups selectively adsorbs a cationic dye,
methylene blue, over an anionic dye.
PMID- 28416889
TI - Predicting toddler temperamental approach-withdrawal: Contributions of early
approach tendencies, parenting behavior, and contextual novelty.
AB - Research suggests that temperamental approach-withdrawal is subject to parenting
influences, but few studies have explored how specific parenting behaviors and
contextual novelty contribute to the observed pattern of effects. The present
study examined associations between infant temperamental approach, mother
behavior while introducing novel objects (12 months) and temperamental approach
withdrawal in toddlerhood (18 months) in a sample of 132 infants (68 males).
Maternal positive affect predicted more toddler approach-withdrawal for high
approach infants and maternal stimulation predicted less toddler approach
withdrawal for low-approach infants; however, these patterns varied with
intensity of novelty in both parenting and toddler outcome contexts. Thus,
maternal behavior may lead to stronger associations between earlier and later
measures of approach-withdrawal; however, these effects are tied to contexts of
measurement.
PMID- 28416890
TI - Relationship between perceived exertion during exercise and subsequent recovery
measurements.
AB - The return towards resting homeostasis in the post-exercise period has the
potential to represent the internal training load of the preceding exercise bout.
However, the relative potential of metabolic and autonomic recovery measurements
in this role has not previously been established. Therefore the aim of this study
was to investigate which of 4 recovery measurements was most closely associated
with Borg's Rating of Perceived Exertion (RPE), a measurement widely acknowledged
as an integrated measurement of the homeostatic stress of an exercise bout. A
heterogeneous group of trained and untrained participants (n = 36) completed a
bout of exercise on the treadmill (3 km at 70% of maximal oxygen uptake) followed
by 1 hour of controlled recovery. Expired respiratory gases and heart rate (HR)
were measured throughout the exercise and recovery phases of the trial with
recovery measurements used to calculate the magnitude of excess post-exercise
oxygen consumption (EPOCMAG), the time constant of the EPOC curve (EPOCtau), 1
min heart rate recovery (HRR60s) and the time constant of the HR recovery curve
(HRRtau) for each participant. RPE taken in the last minute of exercise was
significantly associated with HRR60s (r=-0.69), EPOCtau (r=0.52) and HRRtau
(r=0.43) but not with EPOCMAG. This finding suggests that, of the 4 recovery
measurements under investigation, HRR60s shows modest potential to represent
inter-individual variation in the homeostatic stress of a standardized exercise
bout, in a group with a range of fitness levels.
PMID- 28416891
TI - Session-RPE for quantifying the load of different youth basketball training
sessions.
AB - The aim of the study was to evaluate youth basketball training, verifying the
reliability of the session-RPE method in relation to session duration (< and >=
80 minutes) and workout typology (reduced and high warm-up, conditioning,
technical, tactical, game portions within a single session) categories. Six male
youth basketball players (age, 16.5+/-0.5 years; height, 195.5+/-6.75 cm; body
mass, 93.9+/-10.9 kg; and body mass index, 23.6+/-2.8 kg.m-2) were monitored (HR,
type and duration of workouts) during 15 (66 individual) training sessions (80+/
26 minutes). Edwards' HR method was used as a reference measure of internal
training load (ITL); the CR-10 RPE scale was administered 30 minutes after the
end of each session. The results obtained showed that all comparisons between
different session durations and workout portions revealed effects in term of
Edwards' ITLs except for warm-up portions. Moderate to strong relationships
between Edwards' and session- RPE methods emerged for all sessions (r = .85, P <
.001), player's sessions (r range = .79 - .95, P < .001), session durations (< 80
minutes: r = .67, P < .001; >= 80 minutes: r = .75, P < .001), and workout
portions (r range = .78 - .89, P range = .002 - < .001). The findings indicated
that coaches of youth basketball players can successfully use session-RPE to
monitor the ITL, regardless of session durations and workout portions.
PMID- 28416892
TI - Anthropometric and physical characteristics allow differentiation of young female
volleyball players according to playing position and level of expertise.
AB - The aim of our study was to determine the differences in some anthropometric and
physical performance variables of young Croatian female volleyball players (aged
13 to 15) in relation to playing position (i.e., independent variable) and
performance level within each position (i.e., independent variable). Players were
categorized according to playing position (i.e., role) as middle blockers (n=28),
opposite hitters (n=41), passer-hitters (n=54), setters (n=30), and liberos
(n=28). Within each position, players were divided into a more successful group
and a less successful group according to team ranking in the latest regional
championship and player quality within the team. Height and body mass, somatotype
by the Heath-Carter method, and four tests of lower body power, speed, agility
and upper body power (i.e., dependent variables) were assessed. Players in
different positions differed significantly in height and all three somatotype
components, but no significant differences were found in body mass, body mass
index or measured physical performance variables. Players of different
performance level differed significantly in both anthropometric and physical
performance variables. Generally, middle blockers were taller, more ectomorphic,
less mesomorphic and endomorphic, whereas liberos were shorter, less ectomorphic,
more mesomorphic and endomorphic than players in other positions. More successful
players in all positions had a lower body mass index, were less mesomorphic and
endomorphic, and more ectomorphic than less successful players. Furthermore, more
successful players showed better lower body power, speed, agility and upper body
power. The results of this study can potentially provide coaches with useful
indications about the use of somatotype selection and physical performance
assessment for talent identification and development.
PMID- 28416894
TI - Letter to the editor: A genetic-based algorithm for personalized resistance
training.
AB - In a recent paper entitled "A genetic-based algorithm for personalized resistance
training", Jones et al. [1] presented an algorithm of 15 performance-associated
gene polymorphisms that they propose can determine an athlete's training response
by predicting power and endurance potential. However, from the design of their
studies and the data provided, there is no evidence to support these authors'
assertions. Progress towards such a significant development in the field of sport
and exercise genomics will require a paradigm shift in line with recent
recommendations for international collaborations such as the Athlome Project (see
www.athlomeconsortium.org). Large-scale initiatives, involving numerous multi
centre and well-phenotyped exercise training and elite performance cohorts, will
be necessary before attempting to derive and replicate training and/or
performance algorithms.
PMID- 28416893
TI - Letter to the editor: Are the doors opened to a genetic-based algorithm for
personalized resistance training?
PMID- 28416895
TI - A response to letter to the editor: A genetic-based algorithm for personalized
resistance training.
PMID- 28416896
TI - ACTN3 R577X genotype and performance of elite middle-long distance swimmers in
China.
AB - The ACTN3 gene is one of the genes that have a potential influence on physical
performance. Studies have shown that the 577R genotype of ACTN3 is more prevalent
in sprint athletes, while the 577X genotype is more prevalent in endurance
athletes. In swimming, both power and endurance related phenotypes are equally
needed for swimmers to excel at the elite level. Therefore, the ACTN3 R577X
polymorphism may become a genetic marker for swimmers. The study aimed to examine
the association of the ACTN3 R577X genotype with the performance of elite middle
long distance (MLD) swimmers. The distributions of the ACTN3 R577X (rs1815739)
genotype and allele were examined in a general population (206) and a group of
elite MLD swimmers (160) in China by using PCR-RFLP and TOF. Compared with the
general population, the elite MLD swimmers, especially the females, had a higher
frequency of the RR genotype. The swimmers had a higher frequency of the R allele
than the general population. However, the difference was not statistically
significant. After being stratified by performance, the difference of the R
allele frequency between the international master athletes and the general
population was statistically significant. The elite MLD swimmers had a higher
frequency of the RR genotype than the RX+XX genotype compared with the general
population. The ACTN3 R577X polymorphism was associated with the performance of
elite MLD swimmers in China. The SNP R577X could be used as a biomarker for
selecting elite MLD swimmers in China.
PMID- 28416897
TI - Total bilirubin in athletes, determination of reference range.
AB - The purpose of this study was to determine a typical reference range for the
population of athletes. Results of blood tests of 339 athletes (82 women and 257
men, aged 18-37 years) were retrospectively analysed. The subjects were
representatives of different sports disciplines. The measurements of total
bilirubin (BIT), iron (Fe), alkaline phosphatase (ALP), alanine aminotransferase
(ALT) and gamma-glutamyltransferase (GGT) were made using a Pentra 400
biochemical analyser (Horiba, France). Red blood cell count (RBC), reticulocyte
count and haemoglobin concentration measurements were made using an Advia 120
haematology analyser (Siemens, Germany). In groups of women and men the
percentage of elevated results were similar at 18%. Most results of total
bilirubin in both sexes were in the range 7-14 MUmol.L-1 (49% of women and 42% of
men). The highest results of elevated levels of BIT were in the range 21-28
MUmol.L-1 (12% of women and 11% of men). There was a significant correlation
between serum iron and BIT concentration in female and male athletes whose serum
total bilirubin concentration does not exceed the upper limit of the reference
range. Elevated concentrations of total bilirubin appear to be due to changes
caused by regular exercise. The obtained upper limit of the reference range for
total bilirubin concentration in the group of athletes is 29.0 MUmol.L-1. It
seems reasonable to use dedicated reference values for total bilirubin
concentration in relation to the group of athletes.
PMID- 28416898
TI - SIgA response and incidence of upper respiratory tract infections during
intensified training in youth basketball players.
AB - The aim of the present study was to examine the effect of an intensified training
phase followed by a tapering phase on the salivary immunoglobulin A concentration
and on the upper respiratory tract infection (URTI) symptoms in young male
basketball players. The session rating of perceived exertion method was used to
quantify the internal training load, and the Wisconsin Upper Respiratory Symptom
Survey-21 questionnaire was used to assess URTI symptoms. The Yo-Yo IR1 test and
saliva collection were carried out at the beginning of the study (T1), after the
intensified phase (T2), and after tapering (T3). A higher internal training load
was observed for the intensified phase compared with the tapering phase (t=19.10;
p<0.001), and a significant decrease in salivary immunoglobulin A concentration
was detected (F=7.48; p=0.004) at T3 compared to T1 (p=0.02) and T2 (p=0.05).
However, there was no significant difference between phases for severity of URTI
(chi2= 2.83; p=0.242). The Yo-Yo IR1 test performance increased from T2 and T3
compared to T1 (F=58.24; p<0.001). There was no significant effect of aerobic
fitness level on salivary immunoglobulin A response (F=1.095; p=0.344). In
summary, the present findings suggest that an intensified training load followed
by a tapering period negatively affects the mucosal immune function with no
significant change in severity of URTI in young basketball players.
PMID- 28416899
TI - The efficacy of a discontinuous graded exercise test in measuring peak oxygen
uptake in children aged 8 to 10 years.
AB - As children's natural activity patterns are highly intermittent in nature, and
characterised by rapid changes from rest to vigorous physical activity,
discontinuous exercise tests may be considered ecologically valid for this
population group. This study compared the peak physiological responses from a
discontinuous and continuous graded exercise test (GXT_D, GXT_C, respectively)
during treadmill exercise in children. Twenty-one healthy children (9.6 +/- 0.6
y) completed GXT_D and GXT_C in a randomised order, separated by 72-hours.
Following each GXT, and after a 15-minute recovery, participants completed a
verification test at 105% of the velocity attained at peak oxygen consumption
(VO2peak). There were no differences in VO2peak (55.3 +/- 8.2 cf. 54.4 +/- 7.6
mL.kg-1.min-1) or maximal heart rate (202 +/- 10 cf. 204 +/- 8 b.min-1) between
GXT_C and GXT_D, respectively (P>.05). Peak running speed (10.7 +/- 0.9 cf. 12.1
+/- 1.3 km.h-1) and respiratory exchange ratio (1.04 +/- 0.05 cf. 0.92 +/- 0.05)
were however different between tests (P<.001). Although similar peak
physiological values were revealed between GXT_C and the corresponding
verification test (P>.05), VO2peak (53.3 +/- 7.3 mL.kg-1.min-1) and heart rate
(197 +/- 13 b.min-1) were significantly lower in the GXT_D verification test
(P<.05). In conclusion, a discontinuous GXT is an accurate measure of VO2peak in
children aged 8 to 10 years and may be a valid alternative to a continuous GXT,
despite its longer duration.
PMID- 28416900
TI - Measurement errors when estimating the vertical jump height with flight time
using photocell devices: the example of Optojump.
AB - Common methods to estimate vertical jump height (VJH) are based on the
measurements of flight time (FT) or vertical reaction force. This study aimed to
assess the measurement errors when estimating the VJH with flight time using
photocell devices in comparison with the gold standard jump height measured by a
force plate (FP). The second purpose was to determine the intrinsic reliability
of the Optojump photoelectric cells in estimating VJH. For this aim, 20 subjects
(age: 22.50+/-1.24 years) performed maximal vertical jumps in three modalities in
randomized order: the squat jump (SJ), counter-movement jump (CMJ), and CMJ with
arm swing (CMJarm). Each trial was simultaneously recorded by the FP and Optojump
devices. High intra-class correlation coefficients (ICCs) for validity (0.98
0.99) and low limits of agreement (less than 1.4 cm) were found; even a
systematic difference in jump height was consistently observed between FT and
double integration of force methods (-31% to -27%; p<0.001) and a large effect
size (Cohen's d>1.2). Intra-session reliability of Optojump was excellent, with
ICCs ranging from 0.98 to 0.99, low coefficients of variation (3.98%), and low
standard errors of measurement (0.8 cm). It was concluded that there was a high
correlation between the two methods to estimate the vertical jump height, but the
FT method cannot replace the gold standard, due to the large systematic bias.
According to our results, the equations of each of the three jump modalities were
presented in order to obtain a better estimation of the jump height.
PMID- 28416901
TI - Mechanical efficiency in children with different body weight: a longitudinal
assessment of the quality cohort.
AB - Net mechanical efficiency (MEnet), which reflects the body's ability to transfer
energy above resting levels in external work, is similar in young children
regardless of their body weights. However, it is unclear whether MEnet remains
stable during growth and maturation. We sought to determine whether net
mechanical efficiency (MEnet) changes over a period of 3 years in children and to
identify the factors associated with possible changes. A total of 169 children
participating in the QUALITY (Quebec Adipose and Lifestyle InvesTigation in
Youth) cohort completed an incremental cycling test, resulting in the same
maximal power output during both visits. For MEnet, resting energy consumption
was subtracted from total energy consumption at each exercise stage. Physical
activity was measured using an accelerometer worn for 7 days. Participants were
measured at year one and again two years later. MEnet did not differ across the
visits at the 25, 50 and 75 watt stages. However, the participants exhibited
lower MEnet values at follow-up for the 100 and 125 W stages (23(3) vs. 20(1)%;
25(4) vs. 20(2)%; p<0.01). Declines in MEnet correlated positively with declines
in moderate-to-vigorous physical activity levels (r=0.78, p<0.05). The declines
in moderate-to-vigorous physical activity levels across the visits were
identified as significant predictors of MEnet changes at 100 and 125 W over 3
years, accounting for 22% of the relationship. In children, MEnet, determined at
high exercise intensity, decreases within a period of three years, and the
decrement appeared to be related to moderate-to-vigorous physical activity.
PMID- 28416902
TI - A first look into the influence of triathlon wetsuit on resting blood pressure
and heart rate variability.
AB - The purpose of this study was to investigate the effects of wearing a wetsuit on
resting cardiovascular measures (blood pressure (BP), heart rate variability
(HRV)). The influence of position (upright, prone) and wetsuit size were also
explored. Participants (n=12 males, 33.3+/-12.1 years) had BP and HRV measured
during six resting conditions: standing or prone while not wearing a wetsuit
(NWS), wearing the smallest (SWS), or largest (LWS) wetsuit (based upon
manufacturer guidelines). Heart rate was recorded continuously over 5-mins; BP
was measured three times per condition. HRV was represented by the ratio of low
(LF) and high (HF) frequency (LF/HF ratio); mean arterial pressure (MAP) was
calculated. Each dependent variable was analyzed using a 2 (position) x 3
(wetsuit) repeated measures ANOVA (alpha=0.05). Neither HRV parameter was
influenced by position x wetsuit condition interaction (p>0.05) and MAP was not
influenced by position (p=0.717). MAP and LF/HF ratio were both influenced by
wetsuit condition (p<0.05) with higher during SWS than NWS (p=0.026) while LF/HF
ratio was lower during SWS compared to NWS (p=0.032). LF/HF ratio was influenced
by position being greater during standing vs. prone (p=0.001). It was concluded
that during resting while on land (i.e., not submerged in water), wearing a
small, tight-fitting wetsuit subtlety altered cardiovascular parameters for
healthy, normotensive subjects.
PMID- 28416903
TI - Effects of strength training with blood flow restriction on torque, muscle
activation and local muscular endurance in healthy subjects.
AB - The present study aimed to analyse the effects of six weeks of strength training
(ST), with and without blood flow restriction (BFR), on torque, muscle
activation, and local muscular endurance (LME) of the knee extensors. Thirty
seven healthy young individuals were divided into four groups: high intensity
(HI), low intensity with BFR (LI+BFR), high intensity and low intensity + BFR
(COMB), and low intensity (LI). Torque, muscle activation and LME were evaluated
before the test and at the 2nd, 4th and 6th weeks after exercise. All groups had
increased torque, muscle activation and LME (p<0.05) after the intervention, but
the effect size and magnitude were greater in the HI, LI+BFR and COMB groups. In
conclusion, the groups with BFR (LI+BFR and COMB) produced magnitudes of muscle
activation, torque and LME similar to those of the HI group.
PMID- 28416904
TI - Estimating life expectancy of the population in Cyprus with the use of life
tables.
AB - AIM: The aim of this study was to investigate the life expectancy of the Cypriot
population between 1986 and 2012. MATERIAL AND METHODS: We used the data reported
in the annual editions of the Statistical Service of Cyprus and constructed life
tables of the Cypriot population between 1986 and 2012. RESULTS: For both
genders, and for males and females separately, in the year 1986 life expectancy
accounted 74.47, 72.2, and 76.76 years respectively, while in 2012 values
increased to about 81.28, 79.02, and 83.50 years respectively. The longitudinal
trend of life expectancy is to increase over the calendar years. The largest
increase in life expectancy occurred at birth and was approximately seven years
for both males and females. Until the age of 55, this gain was approximately six
years of life. From age 60 to 65 years, the gain was about five years of life,
and in the oldest age groups, the gain was four years of life. The values
corresponding to male were lower compared to those corresponding to females, with
the exception of the age 0 (at birth). CONCLUSIONS: A significant increase in
life expectancy of the Cypriot population was noted in the period 1986-2012,
which was more obvious at younger ages and in females. Hippokratia 2016, 20(2):
99-103.
PMID- 28416905
TI - Transitory evoked otoacoustic emission (TEOAE) and distortion product otoacoustic
emission (DPOAE) outcomes from a three-stage newborn hearing screening protocol.
AB - OBJECTIVE: Comparison of the efficacy of Transitory Evoked Otoacoustic Emissions
(TEOAEs) and Distortion Product Otoacoustic Emissions (DPOAEs) in a neonatal
hearing screening protocol, based on a three-stage strategy. METHODS: In the
first stage, a hearing screening using both evoked emissions was conducted in
3,480 neonates from March 2006 through January 2012. Both TEOAEs and DPOAEs were
recorded. Neonates, who did not undergo the test before being discharged, were
examined within 30 days at a scheduled appointment. Follow-up of the referred
newborns (second-stage screening) was performed as an outpatient re-screening,
within a month. The third-stage evaluation, i.e., the diagnostic testing,
included a clinical otolaryngological examination, high-frequency tympanometry at
1,000 Hz and Auditory Brainstem Response (ABR) measurements. RESULTS: A total of
3,480 (97%) newborns (n =1,765 males) out of 3,595 infants were enrolled in the
study. In the first-stage evaluation, 8.9 % of the infants were referred
according to TEOAEs, while the percentage of the referred infants for
DPOmicronAlphaEpsilons was 25.7 %. At this initial assessment stage, the
specificity of TEOAES and DPOAEs were determined as 92% and 75%, while positive
predictive values (PPV) were 3.8 % and 1.3 %, respectively. In the second stage
of evaluation, the specificity of TEOAES and DPOAEs were 86 % and 76 %, while the
PPV increased to 18 % and 15 %, respectively. CONCLUSIONS: With a lower follow-up
rate, TEOAEs testing was significantly easier to perform and more reliable
compared to the DPOAEs test. Hippokratia 2016, 20(2): 104-109.
PMID- 28416906
TI - Metabolic syndrome in patients with chronic obstructive pulmonary disease:
frequency and relationship with systemic inflammation.
AB - BACKGROUND: Metabolic syndrome (MetS) is frequent in patients with chronic
obstructive pulmonary disease (COPD). Systemic inflammation plays an important
role in both COPD and MetS. The aim of this study was to assess the frequency of
MetS in COPD patients and to evaluate the status of systemic inflammation in COPD
patients with MetS and those without MetS. METHODS: This cross-sectional study
included 98 consecutive stable COPD patients. The MetS was defined using the
criteria of the International Diabetes Federation. Components of MetS and markers
of systemic inflammation: C-reactive protein (CRP), fibrinogen, and leukocyte
count were measured. All patients underwent spirometry. The staging of COPD was
made according to the Global initiative for chronic obstructive lung disease
(GOLD) criteria. RESULTS: MetS was present in 37.8 % COPD patients. The
frequencies of MetS in patients with GOLD stages I, II, III, and IV were 33.3 %,
48.8 %, 31.6 %, and 23.1 %, respectively. MetS frequencies were not significantly
different between GOLD stages. The multivariate logistic regression analysis
revealed leukocyte count and CRP level as significant independent predictors of
the presence of Mets in COPD patients (OR =1.321, 95%CI: 1.007-1.628, p =0.009
and OR =1.184, 95%CI: 1.020-1.376, p =0.027 respectively). CONCLUSIONS: This
study shows that MetS is frequent in patients with COPD. Systemic inflammatory
markers are higher in COPD patients with MetS than in patients without MetS.
These findings suggest that physicians should screen COPD patients for associated
MetS and elevated circulatory inflammatory markers. Management of these disorders
should reduce the risk of cardiovascular morbidity and mortality in these
patients. Hippokratia 2016, 20(2):110-114.
PMID- 28416907
TI - Self-reported autonomic symptoms in Parkinson's disease: properties of the SCOPA
AUT scale.
AB - BACKGROUND AND AIM: Autonomic symptoms in Parkinson's disease (PD) are very
common and contribute to the severity of patient's disability. We evaluated the
occurrence of autonomic symptoms in Greek patients with PD utilizing the Scales
for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT), a
specific 23-item self-completed questionnaire for the assessment of autonomic
dysfunction in patients with PD. SUBJECTS AND METHODS: One hundred and sixty-one
PD patients and forty matched controls were enrolled in the study. Clinical
assessment was performed with the Hoehn and Yahr scale. Patients completed a
demographic questionnaire, the Non-Motor Symptoms Questionnaire (NMSQuest), the
Parkinson's Disease Questionnaire (PDQ-39) and the SCOPA-AUT scale which was
properly translated into Greek and validated for the study. RESULTS: SCOPA-AUT
scale showed a good reliability profile and correlated well with other measures
for non-motor symptoms and health-related quality measures in PD patients. PD
patients scored higher than controls in the total SCOPA -AUT score (mean score
11.9 versus 6.4). Patients reported problems in many items of the SCOPA-AUT, but
the most common autonomic symptoms emerged in the Urinary and the
Gastrointestinal domains. Especially sialorrhea, constipation, straining for
defecation, incontinence and nocturia differentiated patients from controls.
Furthermore, mean total SCOPA-AUT score correlated with duration and severity of
the disease. CONCLUSION: Autonomic symptoms in PD are too important to remain
undetected. By incorporating into everyday practice the use of suitable and
reliable questionnaires, physicians will be able to adequately detect and manage
these symptoms. Hippokratia 2016, 20(2):115-120.
PMID- 28416909
TI - Factors predicting a positive capsule endoscopy in past overt obscure
gastrointestinal bleeding: a multicenter retrospective study.
AB - OBJECTIVES: Capsule endoscopy (CE) remains the examination of choice for the
investigation of obscure gastrointestinal bleeding. Although the factors
predicting positive CE findings in the overall obscure gastrointestinal bleeding
have been investigated, the clinical characteristics that predict a positive CE
in patients with past overt obscure gastrointestinal bleeding (OOGIB) have not
been systematically studied. METHODS: Between September 2004 and December 2013,
262 patients underwent CE for evaluation of past OOGIB after negative upper and
lower endoscopy, and other diagnostic modalities. Patients' records were
retrospectively reviewed to assess the factors that could possibly predict
positive CE findings. RESULTS: Two hundred and twenty four patients with a median
age of 70 years (range: 17-87) were enrolled in the final analysis and were
divided into two groups; those who had positive (group A: 118 patients) and those
who had negative CE findings (group B: 106 patients). The overall diagnostic
yield of CE was 52.68 %. Multivariate analysis demonstrated that age >65 years,
anticoagulant use, antiplatelet use, and non-steroidal anti-inflammatory drugs
use were independent predictive factors for positive findings on CE. Of the 118
patients with positive CE, therapeutic interventions were performed in 56
patients (47.46 %). Recurrence of bleeding presented in nine patients of group B
compared with 39 patients of group A (p <0.001). CONCLUSIONS: Certain clinical
characteristics predict a positive CE in patients with past OOGIB. Patients with
OOGIB and negative CE had a considerably lower rebleeding rate, and further
invasive investigational procedures may be adjourned or may not be required,
though such recommendation warrants further validation. Hippokratia 2016, 20(2):
127-132.
PMID- 28416908
TI - Incidence and factors predisposing to retinopathy of prematurity in inborn
infants less than 32 weeks of gestation.
AB - PURPOSE: Retinopathy of prematurity (ROP) is a visual-impairing disorder of the
developing retinal vasculature in premature infants. Recent advances in neonatal
care have led to an increase in the vulnerable premature population. The aim of
this retrospective study was to assess the incidence of ROP and its risk factors
according to degree of prematurity. METHODS: Data from a sequence of 1,562
infants <32 weeks of gestational age, admitted to the Jewish General Hospital
Neonatal Intensive Care Unit, a tertiary care perinatal center in Montreal,
Canada, were reviewed to determine the incidence and risk factors of ROP.
Perinatal risk factors for ROP were analyzed using univariate and multivariate
analyses in four consecutive gestational age (GA) groups (24-25+6/7weeks, 26
27+6/7 weeks, 28-29+6/7 weeks and 30-31+6/7 weeks). RESULTS: The overall
incidence in our study was 15.6 %. Severe ROP, defined as stage 3 or plus disease
was detected in 5.2 % of the neonates screened. In the univariate analyses, many
risk factors in each GA group were found to have a significant association with
ROP. On subsequent multivariate logistic regression analysis, birth weight, small
for gestational age, the presence of patent ductus arteriosus (PDA), sepsis,
necrotizing enterocolitis (NEC), and mechanical ventilation >7 days were
independently associated with the development of ROP. Birth weight was
consistently an independent risk factor for ROP in all GA groups. CONCLUSION: Our
study confirmed the importance of birth weight as an independent ROP risk factor.
Sepsis, NEC, PDA, and prolonged mechanical ventilation have been shown to be
independent risk factors in the different gestational age groups. Hippokratia
2016, 20(2): 121-126.
PMID- 28416910
TI - The role of serum osteoprotegerine in metastatic prostate cancer - a case control
study.
AB - INTRODUCTION: Prostate cancer is one of the most common malignant neoplastic
diseases in men. Early control of the disease progression contributes
significantly to survival rates and patients' quality of life. Osteoprotegerin is
a dimeric glycoprotein, which affects bone metabolism and inhibits
osteoclastogenesis. In the present study, we evaluated the expression of
osteoprotegerin in the serum of prostate cancer patients with or without skeletal
metastases. METHODS: The expression of serum osteoprotegerin, as measured by
enzyme-linked immunosorbent assay, has been studied in 82 patients with locally
controlled prostate cancer, in 49 patients with metastatic bone disease and in a
control group of 41 healthy males. At sampling time 65/131 of included patients
were newly diagnosed, while 66/131 patients were already under hormonal therapy.
All eligible prostate cancer patients had histologically confirmed malignancy.
Serum total prostate-specific antigen (PSA) was determined by an
immunoradiometric assay. We investigated the expression of osteoprotegerin in
hormone-dependent and hormone-refractory prostate cancer and its relation to
disease progression. RESULTS: Among the 131 patients with prostate cancer, higher
osteoprotegerin and PSA concentrations have been observed in metastatic bone
patients' sera (p <0.001). ROC analysis between the metastatic and locally
controlled prostate cancer patients has shown a statistically significant area
curve (p <0.001) and a cut-off limit of 89.6 pg/ml. Moreover, 15.3 % of patients
became hormone-resistant, with osteoprotegerin values significantly increased
compared with hormone-sensitive prostate cancer patients (p <0.001). CONCLUSIONS:
It seems that elevated levels of serum osteoprotegerin in patients with prostate
cancer reflect the bone metastatic extent and may potentially be used in
metastatic patients' follow-ups. Hippokratia 2016, 20(2): 133-138.
PMID- 28416911
TI - Quality of life of patients with advanced cancer treated in a regional hospital
in Greece.
AB - BACKGROUND: Quality of life (QoL) assessment contributes to the better care of
cancer patients. The aim of the study was to determine QoL among treated patients
with advanced cancer (ACPs) in the island of Crete, Greece, their satisfaction
with the given care and to evaluate possible differences in QoL between in- and
day care clinic patients. METHODS: The QoL of 95 Greek ACPs with breast, lung,
and colon cancer were evaluated using the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3), and
its Breast (QLQ-BR23) and Lung (QLQ-LC13) Cancer modules, while their
satisfaction with the given care was evaluated with a 10-point questionnaire.
Multiple linear regression analysis was used to assess associations of QoL with
patients' demographic and clinical characteristics. RESULTS: Patients reported
moderate global health status/QoL (62.6) and higher cognitive, physical, and
emotional scores (75.4, 66.8, and 66.6 respectively). In symptoms scales/items,
all patients had mean scores <50 while higher mean scores were observed for
fatigue (41.8) and dyspnea (36.2). No significant differences in functioning and
symptoms scales were found between different cancer types. Sexual functioning in
QLQ-BR23 and alopecia in QLQ-LC13 severely affected QoL. Hospitalized patients
reported worse mean global QoL than those visiting the day care clinic (55.6
versus 67.6, p =0.017), as well as in all parameters described by QLQ-C30. Most
patients were satisfied with the given care (>=8/10, 74.2% of patients).
CONCLUSIONS: ACPs in the present study were found to have an overall good QoL,
functioning, and symptoms scores and were satisfied with the given care. Fatigue,
dyspnea, alopecia, and sexual dysfunction were found to be among the most
frequently reported distressing symptoms. Hippokratia 2016, 20(2): 139-145.
PMID- 28416912
TI - Evaluation of malnutrition detected with the Nutritional Risk Screening 2002 (NRS
2002) and the quality of life in hospitalized patients with chronic obstructive
pulmonary disease.
AB - BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD)
have impaired quality of life, but the relationship between their nutritional
status and quality of life has not been established. The aim of this study was to
determine the relationship between quality of life and nutritional status in
hospitalized COPD patients. METHODS: Demographic data, quality of life and
nutritional status of 90 inpatients with a mean age of 68.76 +/- 10.85 years were
enrolled in the study. The Nutritional Risk Screening 2002 (NRS-2002) tool was
used to evaluate their nutritional status. The quality of life was assessed using
the Short Form-36 (SF-36) questionnaire. The correlation analysis was used for
the relationship between SF-36 subscales and nutritional status variables.
RESULTS: Of the 90 COPD patients included in the study, 54.4 % were men, and 45.6
% were women. Moderate, severe, and very severe COPD were detected in 37.8 %,
38.9 %, and 23.3 % of the patients, respectively. At risk of malnutrition were
55.6 % of the 90 COPD patients, whereas 44.4 % were not. The scores for physical
function, physical role functioning, pain, general health, emotional role
functioning, vitality, social function, and mental function subscales were lower
in the patients at risk of malnutrition (p <0.001). There was a statistically
significant negative correlation between malnutrition score and the subscores of
SF-36 related to physical function, physical role functioning, pain, general
health, emotional role functioning, vitality, social function, and mental
function (p <0.001). CONCLUSIONS: COPD patients were found to have a high risk of
malnutrition that adversely affects their quality of life. Therefore, the
evaluation of the nutritional status of COPD patients should be an integral part
of their clinical treatment plans aiming towards improving their quality of life.
Hippokratia 2016, 20(2):147-152.
PMID- 28416913
TI - Long-term response in biochemical markers of bone turnover during enzyme
replacement therapy in a case-series of patients with Gaucher disease type I from
Northern Greece.
AB - BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by
severe skeletal complications. Bone complications are an important cause of
morbidity of GD and are thought to result from imbalance in bone remodeling. The
objective of this case series was to analyze the long-term effect of enzyme
replacement therapy on chemokines MIP-1a and MIP-1b, cytokines IL-3, IL-6, IL-10,
and IL-12, osteoprotegerin (OPG) and osteocalcin (BGP), chitotriosidase,
quantitative ultrasound sonography (QUS), bone magnetic resonance imaging (MRI)
and dual-energy X-ray absorptiometry (DXA) in patients with GD in Northern
Greece. In addition, the study aimed in investigating possible relationship
between the above mentioned parameters. PATIENTS AND METHODS: Seven patients with
GD type I (three males and four females) were included in the study. Mean age was
26.29 +/- 15.34 years (range 7-47 years). Six patients were receiving enzyme
replacement therapy (ERT), with 40-60 IU/kg of imiglucerase weekly, for a mean
period of 36 months prior to study initiation. One patient started ERT after his
inclusion in the study. The levels of MIP-1a, MIP-1b, IL-3, IL-6, IL-10, IL-12,
OPG, BGP, chitotriosidase, bone imaging parameters assessed with two different
techniques (QUS and DXA) and MRI data were estimated at baseline (T0) and after
two years on ERT. RESULTS: Chitotriosidase, MIP-1a, and IL-6 levels decreased in
all patients after two years of ERT (p =0.05). In contrast, OPG and BGP levels
increased (p =0.04 and p =0.02, respectively). Bone mineral density (BMD)
demonstrated a progressive improvement with regards to the Z-score in all
patients (p =0.05). The decrease in the plasma levels of MIP-1a strongly
correlated with a decrease in the plasma levels of chitotriosidase. Additionally,
decreased plasma levels of IL-6 were correlated with increased Z-score both at
baseline (T0) as well as two years later, in all patients. There was no
correlation between MRI findings and any inflammatory biomarker. CONCLUSIONS:
Measurement of serum markers in patients with GD under ERT could be used as an
auxiliary tool in the monitoring of bone involvement, in combination with MRI
imaging and BMD. However, larger studies involving higher numbers of GD patients
are needed to confirm these conclusions. Hippokratia 2016, 20(2): 153-159.
PMID- 28416914
TI - Atrial fibrillation causing ST elevation myocardial infarction due to coronary
embolism: case report and review of the literature.
AB - BACKGROUND: Atrial fibrillation is a rare but important nonatherosclerotic cause
of ST elevation myocardial infarction. CASE DESCRIPTION: We report the case of a
69 years old woman who presented to our hospital with ST elevation myocardial
infarction and permanent atrial fibrillation and eventually treated with thrombus
aspiration from the left descending coronary artery. CONCLUSION: We have to
notice the importance of the appropriate antithrombotic treatment in atrial
fibrillation to prevent systemic embolism. In selected cases with ST elevation
myocardial infarction due to coronary embolism, aspiration thrombectomy with or
without balloon dilatation or stenting can be safely performed. Hippokratia 2016,
20(2):160-162.
PMID- 28416915
TI - Hypokalemia-induced cardiac arrest in a Duchenne muscular dystrophy patient.
AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive myopathic
disorder, inherited as X-linked recessive traits, in which muscle weakness is the
primary symptom. Correlation between DMD and hypokalemia is reported in only
three case reports. Recent investigations have focused on the nutritional
management of patients with DMD. However, there are no data regarding
recommendations on potassium intake. Description of case: We report the case of a
15-year-old male patient with DMD, who developed sudden cardiac arrest following
severe hypokalemia (K: 1.3 mEq/L) during a lower respiratory tract infection.
Hypokalemia was gradually corrected with intravenous potassium chloride. The
patient, after a prolonged hospitalization due to hypoxic encephalopathy, was
discharged from the Intensive Care Unit (ICU) on mechanical ventilation.
CONCLUSION: Severe hypokalemia is a rare complication of DMD, with potentially
lethal consequences. Therefore, in patients with DMD, potassium levels should be
closely monitored and adjusted with appropriate diet or potassium supplements as
needed. Hippokratia 2016, 20(2): 163-165.
PMID- 28416916
TI - Concentration-related mydriasis in a patient with renal dysfunction treated with
phenytoin.
AB - INTRODUCTION: There is very limited evidence concerning phenytoin-related
mydriasis. CASE REPORT: A 59-year-old male was hospitalized in the intensive care
unit due to a head injury. During his hospitalization, phenytoin was
administrated. Some days later he presented bilateral mydriasis. At that time he
had impaired creatinine clearance 7 ml/min, albumin levels 3.4 gr/dl, and
phenytoin serum concentration 19.94 MUg/dl. Evaluation with brain computed
tomography and magnetic resonance imaging did not reveal any potential cause of
mydriasis, while none of the co-administrated drugs have been reported to cause
significant mydriasis. After initiation of continuous venovenous
hemodiafiltration and discontinuation of phenytoin, mydriasis was reversed.
CONCLUSION: Clinicians should be aware that mydriasis due to a toxic
concentration of phenytoin may be manifested. Hippokratia 2016, 20(2): 166-168.
PMID- 28416917
TI - Laparoscopic microwave ablation for the management of hemorrhage from ruptured
hepatocellular carcinoma.
AB - BACKGROUND: Treatment of ruptured hepatocellular carcinoma (HCC) focuses on
hemorrhage control and utilizes tumor vascular anatomy to palliate or temporize
selected patients with hepatic artery embolization (HAE). Radiofrequency ablation
(RFA) and microwave ablation (MWA) are feasible alternatives or adjunct
modalities to resection of HCC; the method of energy delivery in MWA allows
uniform coagulative necrosis in shorter time compared with RFA. CASE DESCRIPTION:
We present the case of an 82-year-old man who presented with a ruptured liver
tumor with active intraperitoneal bleeding on angiography. The patient remained
hemodynamically stable with evidence of ongoing bleeding following HAE. Tumor
destruction and definitive hemostasis were obtained with minimally invasive MWA.
CONCLUSION: Tumor rupture remains a negative prognostic factor in the course of
HCC. In select patients, MWA allows definitive hemorrhage control with minimal
surgical morbidity. Hippokratia 2016, 20(2): 169-171.
PMID- 28416918
TI - Selective rehabilitation of peripheral facial palsy for idiopathic and traumatic
palsy.
PMID- 28416919
TI - Lipemia and acute coronary syndrome: when color enlightens the truth.
PMID- 28416920
TI - Interleukin 6 as a potential diagnostic and prognostic biomarker in saliva in
patients with carcinoma of the larynx.
PMID- 28416921
TI - Laparoscopic diagnosis of abdominal tuberculosis.
PMID- 28416922
TI - Prevalence of paraoxonase-1 polymorphisms in diabetes mellitus type 2 Greek
patients.
PMID- 28416923
TI - Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES
Correlated with Type of Fundoplication.
AB - OBJECTIVE: The aim of the present study is to show the predictive value of the
preoperative resting pressure of the lower esophageal sphincter (LES) correlated
with the type of fundoplication (Nissen or Dor) after Heller myotomy in our
series. MATERIALS AND METHODS: From January 1998 to June 2010, 88 patients
affected by esophageal achalasia underwent surgery at our unit. However, our
study focused on a sample of 36 patients, because many data were lost or was
never recorded. Among these, 14 patients underwent laparoscopic Heller myotomy
plus Nissen fundoplication (group N), whereas 22 patients underwent laparoscopic
Heller myotomy plus Dor fundoplication (group D). Clinical evaluation was
performed using a modified DeMeester symptom scoring system consisting of the
assessment of three symptoms: dysphagia, regurgitation, and heartburn. To each
symptom was assigned a score from 0 to 3, depending on its severity, and the
reduction in the severity of each symptom after surgery was assessed. RESULTS:
The surgical treatment is considered to be effective (p<0.0001). The preoperative
resting pressures of LES were compared by Student's t-test, and it was found that
patients who reported a greater improvement in the dysphagia symptom had a
preoperative average pressure of LES that was significantly higher than that in
other patients in both group N (p=0.03) and group D (p=0.01; p=0.003; p=0.001).
The Dor treatment was shown to be more effective than the Nissen treatment
(p<0.0001). CONCLUSION: The preoperative resting pressure of LES is a predictive
factor of surgical success both before Dor fundoplication and before Nissen
fundoplication, but its predictive power is influenced by the chosen type of
fundoplication.
PMID- 28416924
TI - Comparison of Second and Third-Generation Nails in the Treatment of
Intertrochanteric Fracture: Screws versus Helical Blades.
AB - OBJECTIVE: The aim of this study was to compare the radiological and functional
outcomes of anti-rotation trochanteric nails (ATNs) with proximal femoral nail
anti-rotation (PFNA) in the treatment of intertrochanteric femur fractures in
elderly patients. MATERIALS AND METHODS: In total, 165 intertrochanteric
fractures were treated between January 2007 and January 2010. One hundred forty
patients were included. The operation time, amount of blood loss, fluoroscopy
screening time, and length of hospitalization were recorded. The radiological
position of the implant, quality of fracture reduction, and tip-apex distance
were evaluated, and the postoperative complications as well as functional
condition of the patients were assessed. RESULTS: There were no significant
differences between the ATN and PFNA groups for the presence of general
complications, length of hospitalization, and functional capacity. The mean
operation time, blood loss amount, and fluoroscopy screening time were more in
the ATN group than in the PFNA group. Reoperation was needed for nine and two
patients in the ATN and PFNA groups, respectively, because of implant-related
complications. CONCLUSION: Both ATNs and PFNA were suitable for the fixation of
intertrochanteric fractures, but the risk of complication occurrence and need for
reoperation were found to be higher in patients who were treated with ATNs.
PMID- 28416925
TI - Shear Wave Sonoelastography Findings of Testicles in Chronic Kidney Disease
Patients Who Undergo Hemodialysis.
AB - OBJECTIVE: Chronic kidney disease (CKD) is known to cause significant
deterioration in the function of the testicles and sexual dysfunction in male
patients who undergo hemodialysis. The aim of this study was to show the changes
in the testicles that occur as a result of hypogonadism secondary to CKD and to
analyze the elasticity of the parenchyma by shear wave sonoelastography.
MATERIALS AND METHODS: In our study we included 28 male patients who undergo
dialysis three times per week and 25 healthy volunteers. Firstly, B-mode
ultrasonographic evaluation was performed in both testicles for structural
analysis and to detect the presence of focal lesions. Afterward, the stiffness of
the parenchyma was measured in kilopascals by shear wave sonoelastography.
RESULTS: The CKD group had lower right, left, and mean testicular volumes
(p<0.001). The CKD group also displayed greater right, left, and mean testicular
parenchymal stiffness (p<0.001). CONCLUSION: CKD patients who undergo
hemodialysis demonstrated significant changes in testicular size and stiffness in
comparison to healthy volunteers.
PMID- 28416926
TI - The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on
the Contractions of Rat Thoracic Aorta.
AB - OBJECTIVE: It was suggested that prostaglandins which are synthesized by
cyclooxygenase (COX) enzymes contribute to the actions of angiotensin-converting
enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism and there is an
interaction between ACE signaling pathway and COX enzymes. We aim to investigate
the role of COX enzymes in the effects of losartan, an angiotensin II (Ang II)
receptor antagonist or lisinopril, an ACE inhibitor, on the contractions of rat
thoracic aorta in isolated tissue bath. MATERIALS AND METHODS: Responses of
losartan (10-6, 10-5, 10-4 M), lisinopril (10-6, 10-5, 10-4 M), and non-selective
COX inhibitor dipyrone (10-4, 7 * 10-4, 2 * 10-3 M) alone to the contractions
induced by phenylephrine (Phe) (10-7 M), potassium chloride (KCl) (6 * 10-2 M),
Ang II (10-8 M) and responses of losartan or lisinopril in combination with
dipyrone to the contractions induced by Phe or KCl were recorded. RESULTS: When
used alone, dipyrone and losartan inhibited Phe, KCl, and Ang II-induced
contractions, whereas lisinopril inhibited only Phe and Ang II-induced
contractions. Inhibition of COX enzymes (COX-3, COX-3 + COX-1, COX-1+ COX-2 + COX
3 by dipyrone 10-4, 7 * 10-4, 2 * 10-3 M, respectively) augmented the relaxant
effects of losartan or lisinopril. Also, dipyrone potentiated the effect of
lisinopril on KCl-induced contractions. CONCLUSION: We suggest that dipyrone
increases the smooth-muscle relaxing effects of losartan or lisinopril and that
COX enzyme inhibition may have a role in the enhancement of this relaxation.
PMID- 28416927
TI - Cataract Surgery and Possible Complications in Patients with Pseudoexfoliation
Syndrome.
AB - OBJECTIVE: The aim of this study was to evaluate the demographic characteristics
and intraoperative complications of cataract surgery in patients with
pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: Cases of 225 eyes (80
eyes with pseudoexfoliation and 145 eyes without pseudoexfoliation as the control
group) that underwent phacoemulsification cataract surgery and IOL implantation
at the Silifke State Hospital Ophthalmology Clinic between April 2011 and April
2013 were analysed retrospectively. Patients with a history of previous ocular
surgeries, ocular trauma, uveitis, glaucoma or corneal pathology were not
included in the study. All cataract procedures were performed by the same
surgeon. Patients' age, gender, anterior segment and fundus findings in both
eyes, presence of pseudoexfoliative material, pre- and postoperative day 1
intraocular pressure (IOP) and surgery notes were evaluated. RESULTS: There were
51 (34.7%) males and 29 (38.6%) females among the PEX cataract patients, and 98
(65.3%) male and 47 (61.8%) female controls. The incidence of pseudoexfoliation
was similar in women (38.2%) and men (34.7%) (p=0.660). The mean age was 74.64+/
6.8 in the PEX group and 68.95+/-7.5 in the control group. Mean age was
significantly higher in the PEX group compared to controls (p<0.001). Poor pupil
dilation occurred intra-operatively in 60 (75%) of the patients with
pseudoexfoliation and in 17 (11.7%) of the control patients. Frequency of poor
intraoperative pupil dilation was significantly higher in the PEX group
(p<0.001). Intraoperative vitreous loss occurred in 7 (8.8%) PEX patients and 5
(3.4%) controls, but this difference was statistically insignificant (p=0.090).
CONCLUSION: Surgeons should be aware of the potential complications of cataract
procedures in patients with PEX. Caution should be taken at every stage of the
surgery to prevent these complications, and surgeons should be knowledgeable and
skilful in complication management should they arise.
PMID- 28416928
TI - Comparison of Anesthetic Administration According to Method of Hip Surgery.
AB - OBJECTIVE: The aim of this study is to compare total hip prosthesis (THP),
partial hip prosthesis (PHP), and proximal femoral nail (PFN) patients in terms
of the chosen anesthetic method. METHODS: A total of 850 patients who underwent
hip surgery were divided into 3 groups according to the operation type: PHP
(n=281), PFN (n=393), and THP (n=176). The type of anesthesia administered,
interventions during anesthesia, and complications were retrospectively
evaluated. The groups were compared in terms of patient age, American Society of
Anesthesiologists (ASA) scores, chosen anesthetic method, operation duration,
colloid use during operation, use of antihypertensive medication, use of
vasoconstrictor medication, development of hypotension, blood transfusion
administered, development of cardiac arrest, requirements for intensive care
after operation, and use of a central catheter. RESULTS: In the THP group, the
mean age of patients was significantly lower as compared to the PHP and PFN
groups. The duration of operation was lower in the PFN group as compared to the
other two groups. In the THP group, general anesthesia was significantly high,
while in the PFN group, regional anesthetic administration was high. While
colloid use was greater in the PFN group, the blood transfusion rate was higher
in the THP group. The use of antihypertensive medication was higher in the THP
group as compared to the other groups. CONCLUSION: Although all three anesthetic
methods could be used in hip surgery, the type of anesthesia should be chosen
according to the type of hip surgery considering the duration of operation, age
of the patient, and blood lost during the operation.
PMID- 28416929
TI - Role of Coma Acidosis Malaria Score in Patients with Severe Malaria among Indian
Population: a Tertiary Care Center Experience.
AB - OBJECTIVE: Malaria is a prime public health threat in developing countries like
India. There is an unmet need of a simplified methodology for the purpose of
triage and provision of intensive care to the severely infected patients in these
areas. MATERIALS AND METHODS: We did a prospective study in patients (n=60)
admitted with severe malaria in a single tertiary care center in the state of
Haryana, India. We assessed the role of coma acidosis malaria (CAM) score in
these patients when predicting mortality and morbidity events. Stepwise logistic
regression analysis was applied to identify patients requiring intensive care
based on the CAM score, and the prediction value of the scoring system was
assessed among these patients. RESULTS: Cerebral malaria (measured using the
Glasgow coma scale) and acidosis (base deficit) were the major determinants of
the CAM score. Serum bicarbonate levels and respiratory rates were assessed as
the proxy markers of the base deficit as it is not always available. Morbidity
increased steadily as the CAM scores increased. Sensitivity and negative
predictive value of 100% depicted that the scoring system was able to identify
patients who needed intensive care and accurately exclude the patients who could
be conservatively managed in the ward. Positive predictive values of 73.9%, 68%,
and 80.9% indicated that CAM, bicarbonate-based CAM (BCAM), and respiratory rate
based CAM (RCAM) scores, respectively, could precisely predict the morbidity and
mortality events among patients with CAM scores >=2. CONCLUSION: CAM scores have
precise predictive values in assessing patients with severe malaria. The scoring
system helps in accurate and systemic triage of patients, irrespective of
species, and directs the treating physicians toward vigilant treatment and
emergency care.
PMID- 28416930
TI - What are the Prevalence of Abdominal Aortic Aneurysm in Patients with Chronic
Obstructive Pulmonary Diseases and the Characteristics of These Patients?
AB - OBJECTIVE: To determine the prevalence of abdominal aortic aneurysm (AAA) in
patients with chronic obstructive pulmonary disease (COPD) and to assess the
characteristics of these patients. MATERIALS AND METHODS: Stable COPD patients
(age, >40 years) were included in the study between January 2014 and June 2014.
Patients with acute exacerbations and a previous lung resection were excluded.
Data regarding demographic characteristics were recorded. The modified Medical
Research Council (mMRC) dyspnea scale was used to assess the severity of
breathlessness. The COPD Assessment Test (CAT) was performed. Abdominal aortic
diameter was measured using abdominal ultrasonography (AUS), and AAA was
diagnosed as an aortic diameter of >=30 mm at the renal artery level. RESULTS: In
total, 82 patients were examined. AAA was detected in five (6.1%) patients.
Diabetes mellitus, hypertension, and coronary artery disease were present in four
patients with AAA. The average mMRC score was 3.2+/-0.4, and the mean CAT score
was 18.4+/-6.0. Aneurysmal diameter was >50 mm in four patients and 37 mm in one
patient. Statistically significant differences were found between patient with
AAA and those without AAA with respect to the mean abdominal aortic diameters at
the renal artery and iliac artery levels (p=0.012 and 0.002, respectively).
CONCLUSION: Our findings suggest that AAA is associated with COPD, with a
prevalence rate of 6.1%. AAA is usually asymptomatic until a clinical status of
rupture, which is associated with a higher mortality risk. Early diagnosis of AAA
is lifesaving. In COPD patients, AAA might be easily determined using AUS, which
is a noninvasive and relatively cheap procedure.
PMID- 28416931
TI - Does Neuropathic Pain Affect the Quality of Sleep?
AB - OBJECTIVE: We aimed to evaluate the quality of sleep (QoS) in patients with
neuropathic pain (NP) and to investigate the association between possible QoS
impairment and NP characteristics. MATERIALS AND METHODS: Patients with NP and
controls were examined. Age, sex, NP duration, NP cause (central, peripheral, or
mixed), and pain intensity (with a Likert-type scale and visual analog scale)
were recorded. NP was screened with Douleur Neuropathique 4 questions (DN4), and
QoS was evaluated using the Pittsburg Sleep Quality Index (PSQI). Mann-Whitney U
test and regression analysis were performed to evaluate the data. RESULTS:
Seventy patients with NP and 30 age- and sex-matched controls were included. The
mean age of the patients and controls were 45.04+/-10.21 years and 39.00+/-19.23
years, respectively. Significantly higher scores of sleep latency (p=0.002),
sleep duration (p=0.003), sleep efficiency (p=0.002), sleep disturbance
(p<0.000), daytime dysfunction (p=0.04), and PSQI total were observed in patients
with NP than in controls (p<0.000). In addition, 80% of patients with NP and 37 %
of controls were classified as having poor QoS (p<0.000). Female sex, pain
intensity, and NP duration were found to be factors related to having poor QoS in
patients with NP (p=0.026, p=0.006, and p<0.000, respectively). CONCLUSION: In
our study, 80% of patients with NP had poor QoS regardless of the NP cause.
Female sex, pain severity, and NP duration were found to be factors correlated
with poor QoS. Treatment strategies that target not only NP itself but also
better QoS may contribute to the overall success of management.
PMID- 28416932
TI - Assessment of Endometrial Sampling and Histopathological Results: Analysis of
4,247 Cases.
AB - OBJECTIVE: This study aimed to investigate the relationship between indications
and histopathological results in patients undergoing endometrial sampling.
MATERIALS AND METHODS: Data of 4,247 patients undergoing endometrial sampling due
to non-obstetric gynecological causes between January 2010 and October 2016 were
retrospectively evaluated using the archives of the Gynecology and Obstetrics
Clinic of Konya Training and Research Hospital. RESULTS: The mean age of patients
was 46.8 +/- 8.22 years; the most common indication was
menometrorrhagia/menorrhagia (70.66%), and the least common indication was
cervical polyp (1.34%). The most common histopathological result was
proliferative-secretory endometrium (63.62%); simple hyperplasia with atypia
(0.56%) was determined to be the least common result. Endometrial cancer was
observed more frequently in the post-menopausal bleeding and increased
endometrial thickness group (23.11%). Of patients in whom biopsy was performed,
52.18% had undergone hysterectomy, as a result of which proliferative-secretory
endometrium was most commonly (59.52%) and simple hyperplasia with atypia least
commonly found as the histopathological diagnosis. CONCLUSION: Although sampling
should be performed following endometrial evaluation in patients with post
menopausal bleeding or increased endometrial thickness, according to the results
of our study, routine endometrial biopsy should not be preferred in the other
indications.
PMID- 28416933
TI - Thymectomy in Myasthenia Gravis.
AB - In recent years, thymectomy has become a widespread procedure in the treatment of
myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild
disease classification (Osserman classification 1, 2A). In absence of thymoma or
hyperplasia, there was no relationship between age and gender in remission with
thymectomy. In MG treatment, randomized trials that compare conservative
treatment with thymectomy have started, recently. As with non-randomized trials,
remission with thymectomy in MG treatment was better than conservative treatment
with only medication. There are four major methods for the surgical approach:
transcervical, minimally invasive, transsternal, and combined transcervical
transsternal thymectomy. Transsternal approach with thymectomy is the accepted
standard surgical approach for many years. In recent years, the incidence of
thymectomy has been increasing with minimally invasive techniques using
thoracoscopic and robotic methods. There are not any randomized, controlled
studies which are comparing surgical techniques. However, when comparing non
randomized trials, it is seen that minimally invasive thymectomy approaches give
similar results to more aggressive approaches.
PMID- 28416935
TI - Juvenile Cystic Adenomyoma Mimicking a Uterine Anomaly: a Report of Two Cases.
AB - Juvenile cystic adenomyoma is a rare form of adenomyosis and described as a new
type of mullerian anomaly in literature. We are presenting two cases of juvenile
cystic adenomyoma which were misdiagnosed preoperatively as unicornuate uterus
with haematometra in a non-communicating rudimentary horn. The mainstay of
treatment is complete resection of lesion.
PMID- 28416934
TI - Sepsis and Septic Shock: Current Treatment Strategies and New Approaches.
AB - Sepsis is a complex condition characterized by the simultaneous activation of
inflammation and coagulation in response to microbial insult. These events
manifest as systemic inflammatory response syndrome or sepsis symptoms through
the release of proinflammatory cytokines, procoagulants, and adhesion molecules
from immune cells and/or damaged endothelium. Today, sepsis is a severe
multisystem disease with difficult treatments for its manifestations and high
mortality rates. In the last two decades in particular, many studies have been
conducted on sepsis that cause shock, multiorgan dysfunction, and organ failure
by especially leading to hemodynamic changes. In sepsis, increasing antibiotic
resistance and medicine-resistant hemodynamic changes have resulted in further
research on new treatment modalities in addition to classical treatments. In the
last decade, the sepsis physiopathology has been elucidated. Various therapeutic
agents have been used in addition to antibiotherapy, but no satisfactory results
have been obtained. This review summarizes the sepsis pathophysiology, current
treatment protocols, and new approaches.
PMID- 28416936
TI - Reentrance of Azygos Vein into Azygos Fissure After Pneumothorax.
AB - Empty azygos fissure implies dislocation of the azygos vein to the mediastinal
side of the right upper lobe from azygos fissure, which is usually secondary to
pneumothorax, pleural effusion, parenchymal fibrosis, vertebral collapse or
persistent vomiting. We are presenting here a case where a separated azygos vein
in CT and radiography images was noted. Moreover, in the follow-up images, it
appeared that the complete reexpansion of the right lung resulted in reentrance
of the azygos vein into azygos fissure in its native position.
PMID- 28416937
TI - Expansion of the Rib Head: A Novel Computed Tomographic Feature of Supernumerary
Intrathoracic Ribs.
AB - Intrathoracic ribs are very rare congenital anomalies. Approximately 50 cases
have been reported in the literature till date. They are usually present on the
right side, between the third and eighth ribs without sex predominance. They may
originate from a vertebral body or the proximal or distal part of a rib. In most
cases, they are asymptomatic, but they may be associated with developmental
abnormalities of ribs and vertebrae. The diagnosis is important to prevent
further investigation or intervention. Here we present two rare cases with
supernumerary intrathoracic rib and describe a novel sign, namely expansion of
the rib head. To the best of our knowledge, this is the shortest supernumerary
intrathoracic rib, reported in the literature, on the left side originating from
the head of the second rib, which could have been misdiagnosed as osteochondroma
due to its atypical features.
PMID- 28416939
TI - A Systemic-Onset Juvenile Idiopathic Arthritis Patient with Reduced Anakinra
Treatment Admitted with an Attack.
AB - Interleukin-1 plays an important role in the pathogenesis of systemic-onset
juvenile idiopathic arthritis (SoJIA), and the use of anti-interleukin-1 therapy
has been increasing. We report a case of a 14-year-old male patient with SoJIA.
He was in remission with anakinra treatment for almost 2 years. When we extended
the therapeutic range and decreased the dose (1 mg/kg twice a week), he developed
symptoms mimicking pulmonary embolism and cardiac ischemia. Increased cardiac
enzyme levels and echocardiographic findings were interpreted as myopericarditis.
Pulmonary computed tomography angiography revealed no thrombus. An SoJIA attack
was considered because of high level of acute-phase reactants and clinical
findings. Intensive immunosuppressive therapy with 2 mg/kg/day anakinra was
reinitiated. Clinical and laboratory parameters began to improve on the fifth day
of treatment. Thus, anti-interleukin-1 therapy is very important in patients with
SoJIA. Although the treatment dose was gradually reduced and the therapeutic
range was extended, it is noteworthy that the case progressed to a severe
clinical condition. Broad prospective studies regarding whether, how long, and
for what reasons the dosages of these drugs should be reduced in patients with
SoJIA with no genetic disorders are required.
PMID- 28416938
TI - Combined Systemic and Hysteroscopic Intra-Amniotic Injection of Methotrexate
Associated with Hysteroscopic Resection for Cervical Pregnancy: A Cutting-Edge
Approach for an Uncommon Condition.
AB - This case report of a 36-year-old woman with a diagnosis of cervical pregnancy
describes a novel approach to this rare form of ectopic pregnancy, which was
successfully treated with systemic and local methotrexate (MTX) therapy combined
with hysteroscopic resection. After local and systemic administration of MTX, the
patient underwent hysteroscopic resection of the cervical pregnancy using a 27
bipolar resectoscope with a 4-mm loop. The cervical pregnancy was completely
treated, and satisfactory hemostasis was achieved with electrocoagulation. The
reported case and literature review demonstrate that the combination of systemic
and local (hysteroscopic) administration of MTX with hysteroscopic resection
could offer the possibility of a safe, successful, minimally invasive, and
fertility-sparing surgical treatment for cervical pregnancy.
PMID- 28416940
TI - A Patient with Anterior, Apical, Transitional Zone Prostate Cancer Missed Twice
by Standard Biopsy.
PMID- 28416941
TI - A Family from Turkey with Bartsocas-Papas Syndrome.
PMID- 28416942
TI - The End of a Long Debate: Methylenetetrahydrofolate Reductase Gene Polymorphisms
do not Increase Thrombosis Risk.
PMID- 28416943
TI - Editor's Introduction to This Issue (G&I 15:1, 2017).
PMID- 28416944
TI - Evaluation of Digital PCR as a Technique for Monitoring Acute Rejection in Kidney
Transplantation.
AB - Early detection and proper management of kidney rejection are crucial for the
long-term health of a transplant recipient. Recipients are normally monitored by
serum creatinine measurement and sometimes with graft biopsies. Donor-derived
cell-free deoxyribonucleic acid (cfDNA) in the recipient's plasma and/or urine
may be a better indicator of acute rejection. We evaluated digital PCR (dPCR) as
a system for monitoring graft status using single nucleotide polymorphism (SNP)
based detection of donor DNA in plasma or urine. We compared the detection
abilities of the QX200, RainDrop, and QuantStudio 3D dPCR systems. The QX200 was
the most accurate and sensitive. Plasma and/or urine samples were isolated from
34 kidney recipients at multiple time points after transplantation, and analyzed
by dPCR using the QX200. We found that donor DNA was almost undetectable in
plasma DNA samples, whereas a high percentage of donor DNA was measured in urine
DNA samples, indicating that urine is a good source of cfDNA for patient
monitoring. We found that at least 24% of the highly polymorphic SNPs used to
identify individuals could also identify donor cfDNA in transplant patient
samples. Our results further showed that autosomal, sex-specific, and
mitochondrial SNPs were suitable markers for identifying donor cfDNA. Finally, we
found that donor-derived cfDNA measurement by dPCR was not sufficient to predict
a patient's clinical condition. Our results indicate that donor-derived cfDNA is
not an accurate predictor of kidney status in kidney transplant patients.
PMID- 28416945
TI - A ChIP-Seq Data Analysis Pipeline Based on Bioconductor Packages.
AB - Nowadays, huge volumes of chromatin immunoprecipitation-sequencing (ChIP-Seq)
data are generated to increase the knowledge on DNA-protein interactions in the
cell, and accordingly, many tools have been developed for ChIP-Seq analysis.
Here, we provide an example of a streamlined workflow for ChIP-Seq data analysis
composed of only four packages in Bioconductor: dada2, QuasR, mosaics, and
ChIPseeker. 'dada2' performs trimming of the high-throughput sequencing data.
'QuasR' and 'mosaics' perform quality control and mapping of the input reads to
the reference genome and peak calling, respectively. Finally, 'ChIPseeker'
performs annotation and visualization of the called peaks. This workflow runs
well independently of operating systems (e.g., Windows, Mac, or Linux) and
processes the input fastq files into various results in one run. R code is
available at github: https://github.com/ddhb/Workflow_of_Chipseq.git.
PMID- 28416946
TI - Use of Graph Database for the Integration of Heterogeneous Biological Data.
AB - Understanding complex relationships among heterogeneous biological data is one of
the fundamental goals in biology. In most cases, diverse biological data are
stored in relational databases, such as MySQL and Oracle, which store data in
multiple tables and then infer relationships by multiple-join statements.
Recently, a new type of database, called the graph-based database, was developed
to natively represent various kinds of complex relationships, and it is widely
used among computer science communities and IT industries. Here, we demonstrate
the feasibility of using a graph-based database for complex biological
relationships by comparing the performance between MySQL and Neo4j, one of the
most widely used graph databases. We collected various biological data (protein
protein interaction, drug-target, gene-disease, etc.) from several existing
sources, removed duplicate and redundant data, and finally constructed a graph
database containing 114,550 nodes and 82,674,321 relationships. When we tested
the query execution performance of MySQL versus Neo4j, we found that Neo4j
outperformed MySQL in all cases. While Neo4j exhibited a very fast response for
various queries, MySQL exhibited latent or unfinished responses for complex
queries with multiple-join statements. These results show that using graph-based
databases, such as Neo4j, is an efficient way to store complex biological
relationships. Moreover, querying a graph database in diverse ways has the
potential to reveal novel relationships among heterogeneous biological data.
PMID- 28416947
TI - DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese
and Control Individuals.
AB - Obesity is a highly prevalent, chronic disorder that has been increasing in
incidence in young patients. Both epigenetic and genetic aberrations may play a
role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic
analyses will advance our understanding of the detailed molecular mechanisms
underlying obesity and aid in the selection of potential biomarkers for obesity
in youth. Here, we performed microarray-based DNA methylation and gene expression
profiling of peripheral white blood cells obtained from six young, obese
individuals and six healthy controls. We observed that the hierarchical
clustering of DNA methylation, but not gene expression, clearly segregates the
obese individuals from the controls, suggesting that the metabolic disturbance
that occurs as a result of obesity at a young age may affect the DNA methylation
of peripheral blood cells without accompanying transcriptional changes. To
examine the genome-wide differences in the DNA methylation profiles of young
obese and control individuals, we identified differentially methylated CpG sites
and investigated their genomic and epigenomic contexts. The aberrant DNA
methylation patterns in obese individuals can be summarized as relative gains and
losses of DNA methylation in gene promoters and gene bodies, respectively. We
also observed that the CpG islands of obese individuals are more susceptible to
DNA methylation compared to controls. Our pilot study suggests that the genome
wide aberrant DNA methylation patterns of obese individuals may advance not only
our understanding of the epigenomic pathogenesis but also early screening of
obesity in youth.
PMID- 28416948
TI - Comparative Analysis of Predicted Gene Expression among Crenarchaeal Genomes.
AB - Research into new methods for identifying highly expressed genes in anonymous
genome sequences has been going on for more than 15 years. We presented here an
alternative approach based on modified score of relative codon usage bias to
identify highly expressed genes in crenarchaeal genomes. The proposed algorithm
relies exclusively on sequence features for identifying the highly expressed
genes. In this study, a comparative analysis of predicted highly expressed genes
in five crenarchaeal genomes was performed using the score of Modified Relative
Codon Bias Strength (MRCBS) as a numerical estimator of gene expression level. We
found a systematic strong correlation between Codon Adaptation Index and MRCBS.
Additionally, MRCBS correlated well with other expression measures. Our study
indicates that MRCBS can consistently capture the highly expressed genes.
PMID- 28416949
TI - Circulating Tumor DNA in a Breast Cancer Patient's Plasma Represents Driver
Alterations in the Tumor Tissue.
AB - Tumor tissues from biopsies or surgery are major sources for the next generation
sequencing (NGS) study, but these procedures are invasive and have limitation to
overcome intratumor heterogeneity. Recent studies have shown that driver
alterations in tumor tissues can be detected by liquid biopsy which is a less
invasive technique capable of both capturing the tumor heterogeneity and
overcoming the difficulty in tissue sampling. However, it is still unclear
whether the driver alterations in liquid biopsy can be detected by targeted NGS
and how those related to the tissue biopsy. In this study, we performed whole
exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7
frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS,
the same variant initially identified in the tumor tissue was also detected with
low variant allele frequency. This mutation was subsequently validated by digital
polymerase chain reaction in liquid biopsy. Our result confirm that driver
alterations identified in the tumor tissue were detected in liquid biopsy by
targeted NGS as well, and suggest that a higher depth of sequencing coverage is
needed for detection of genomic alterations in a liquid biopsy.
PMID- 28416950
TI - TRAPR: R Package for Statistical Analysis and Visualization of RNA-Seq Data.
AB - High-throughput transcriptome sequencing, also known as RNA sequencing (RNA-Seq),
is a standard technology for measuring gene expression with unprecedented
accuracy. Numerous bioconductor packages have been developed for the statistical
analysis of RNA-Seq data. However, these tools focus on specific aspects of the
data analysis pipeline, and are difficult to appropriately integrate with one
another due to their disparate data structures and processing methods. They also
lack visualization methods to confirm the integrity of the data and the process.
In this paper, we propose an R-based RNA-Seq analysis pipeline called TRAPR, an
integrated tool that facilitates the statistical analysis and visualization of
RNA-Seq expression data. TRAPR provides various functions for data management,
the filtering of low-quality data, normalization, transformation, statistical
analysis, data visualization, and result visualization that allow researchers to
build customized analysis pipelines.
PMID- 28416951
TI - Spirometry and Bronchodilator Test.
AB - Spirometry is a physiological test for assessing the functional aspect of the
lungs using an objective indicator to measure the maximum amount of air that a
patient can inhale and exhale. Acceptable spirometry testing needs to be
conducted three times by an acceptable and reproducible method for determining
forced vital capacity (FVC). Until the results of three tests meet the criteria
of reproducibility, the test should be repeated up to eight times. Interpretation
of spirometry should be clear, concise, and informative. Additionally, spirometry
should guarantee optimal quality prior to the interpreting spirometry results.
Our guideline adopts a fixed normal predictive value instead of the lower limit
of normal as the reference value because fixed value is more convenient and also
accepts FVC instead of vital capacity (VC) because measurement of VC using a
spirometer is impossible. The bronchodilator test is a method for measuring the
changes in lung capacity after inhaling a short-acting beta-agonist that dilates
the airway. When an obstructive ventilatory defect is observed, this test helps
to diagnose and evaluate asthma and chronic obstructive pulmonary disease by
measuring reversibility with the use of an inhaled bronchodilator. A positive
response to a bronchodilator is generally defined as an increase of >=12% and
>=200 mL as an absolute value compared with a baseline in either forced
expiratory volume at 1 second or FVC.
PMID- 28416953
TI - Response Evaluation of Chemotherapy for Lung Cancer.
AB - Assessing response to therapy allows for prospective end point evaluation in
clinical trials and serves as a guide to clinicians for making decisions. Recent
prospective and randomized trials suggest the development of imaging techniques
and introduction of new anti-cancer drugs. However, the revision of methods, or
proposal of new methods to evaluate chemotherapeutic response, is not enough.
This paper discusses the characteristics of the Response Evaluation Criteria In
Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It
also contains information about possible dilemmas arising from the application of
response assessment by the latest version of the response evaluation method, or
recently introduced chemotherapeutic agents. Further data reveals the problems
and limitations caused by applying the existing RECIST criteria to anti-cancer
immune therapy, and the application of a new technique, immune related response
criteria, for the response assessment of immune therapy. Lastly, the paper
includes a newly developing response evaluation method and suggests its
developmental direction.
PMID- 28416952
TI - Asthma and the Risk of Rheumatoid Arthritis: An Insight into the Heterogeneity
and Phenotypes of Asthma.
AB - Asthma is traditionally regarded as a chronic airway disease, and recent
literature proves its heterogeneity, based on distinctive clusters or phenotypes
of asthma. In defining such asthma clusters, the nature of comorbidity among
patients with asthma is poorly understood, by assuming no causal relationship
between asthma and other comorbid conditions, including both communicable and
noncommunicable diseases. However, emerging evidence suggests that the status of
asthma significantly affects the increased susceptibility of the patient to both
communicable and noncommunicable diseases. Specifically, the impact of asthma on
susceptibility to noncommunicable diseases such as chronic systemic inflammatory
diseases (e.g., rheumatoid arthritis), may provide an important insight into
asthma as a disease with systemic inflammatory features, a conceptual
understanding between asthma and asthma-related comorbidity, and the potential
implications on the therapeutic and preventive interventions for patients with
asthma. This review discusses the currently under-recognized clinical and
immunological phenotypes of asthma; specifically, a higher risk of developing a
systemic inflammatory disease such as rheumatoid arthritis and their
implications, on the conceptual understanding and management of asthma. Our
discussion is divided into three parts: literature summary on the relationship
between asthma and the risk of rheumatoid arthritis; potential mechanisms
underlying the association; and implications on asthma management and research.
PMID- 28416955
TI - Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with
Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease.
AB - BACKGROUND: Recently, increased levels of high-mobility group box 1 protein
(HMGB1) have been identified in various inflammatory conditions and infections.
However, no studies have evaluated the HMGB1 level in nontuberculous
mycobacterial (NTM) lung disease, and compared it to mycobacterial lung disease.
METHODS: A total of 60 patients newly diagnosed with NTM lung disease, 44 culture
positive pulmonary tuberculosis (TB) patients, and 34 healthy controls, were
included in this study. The serum HMGB1 concentrations were quantified using
HMGB1 enzyme-linked immunosorbent assay kits. RESULTS: Serum HMGB1 level in
patients with pulmonary TB or NTM lung disease, was significantly lower than that
of the healthy controls. In addition, the serum HMGB1 level in TB patients was
significantly lower than patients with NTM lung disease. However, the levels in
NTM patient subgroups did not differ according to the causative species, disease
progression, and disease phenotype. CONCLUSION: Although low levels of serum
HMGB1 has the potential to be a marker of mycobacterial lung disease, these
levels were unable to differentiate disease progression and disease phenotype in
NTM lung diseases.
PMID- 28416954
TI - Current Status of Fluoroquinolone Use for Treatment of Tuberculosis in a Tertiary
Care Hospital in Korea.
AB - BACKGROUND: Fluoroquinolones are considered important substitutes for the
treatment of tuberculosis. This study investigates the current status of
fluoroquinolone for the treatment of tuberculosis. METHODS: In 2009, a
retrospective analysis was performed at one tertiary referral center for 953
patients diagnosed with tuberculosis. RESULTS: A total of 226 patients (23.6%),
who received fluoroquinolone at any time during treatment for tuberculosis, were
enrolled in this study. The most common reasons for fluoroquinolone use were
adverse events due to other anti-tuberculosis drugs (52.7%), drug resistance
(23.5%), and underlying diseases (16.8%). Moxifloxacin (54.0%, 122/226) was the
most commonly administered fluoroquinolone, followed by levofloxacin (36.3%,
82/226) and ofloxacin (9.7%, 22/226). The frequency of total adverse events from
fluoroquinolone-containing anti-tuberculosis medication was 22.6%, whereas
fluoroquinolone-related adverse events were estimated to be 2.2% (5/226). The
most common fluoroquinolone-related adverse events were gastrointestinal problems
(3.5%, 8/226). There were no significant differences in the treatment success
rate between the fluoroquinolone and fluoroquinolone-naive groups (78.3% vs.
78.4%, respectively). CONCLUSION: At our institution, fluoroquinolones are
commonly used for the treatment of both multidrug-resistant tuberculosis and
susceptible tuberculosis, especially as a substitute for adverse event-related
drugs. Considering the low adverse event rates and the comparable treatment
success rates, fluoroquinolones seem to be an invaluable drug for the treatment
of tuberculosis.
PMID- 28416956
TI - Mutations in Streptomycin Resistance Genes and Their Relationship to Streptomycin
Resistance and Lineage of Mycobacterium tuberculosis Thai Isolates.
AB - BACKGROUND: Streptomycin (SM) is recommended by the World Health Organization
(WHO) as a part of standard regimens for retreating multidrug-resistant
tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19%
in Thailand. To date, information on SM resistance (SMR) gene mutations
correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In
this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and
their association to SMR and the lineage of M. tuberculosis were explored.
METHODS: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were
identified by spoligotyping. Drug susceptibility profiles were evaluated by the
absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55
SM-susceptible isolates were examined by DNA sequencing. RESULTS: Three rpsL
(Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations
were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was
the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates
(p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and
gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis
Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking
rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C,
615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored.
This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1.
CONCLUSION: Our study suggested that the majority of SMR in M. tuberculosis Thai
isolates were responsible by rpsL and gidB polymorphisms constantly providing the
novel lineage specific makers.
PMID- 28416957
TI - The Need for a Well-Organized, Video-Assisted Asthma Education Program at Korean
Primary Care Clinics.
AB - BACKGROUND: The purpose of this study was to assess the effect of our new video
assisted asthma education program on patients' knowledge regarding asthma and
asthma control. METHODS: Adult asthmatics who were diagnosed by primary care
physicians and followed for at least 1 year were educated via smart devices and
pamphlets. The education sessions were carried out three times at 2-week
intervals. Each education period lasted at most 5 minutes. The effectiveness was
then evaluated using questionnaires and an asthma control test (ACT). RESULTS:
The study enrolled 144 patients (mean age, 56.7+/-16.7 years). Half of the
patients had not been taught how to use their inhalers. After participating in
the education program, the participants' understanding of asthma improved
significantly across all six items of a questionnaire assessing their general
knowledge of asthma. The proportion of patients who made errors while
manipulating their inhalers was reduced to less than 10%. The ACT score increased
from 16.6+/-4.6 to 20.0+/-3.9 (p<0.001). The number of asthmatics whose ACT score
was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude
of improvement in the ACT score did not differ between patients who received an
education session at least three times within 1 year and those who had not. The
majority of patients agreed to the need for an education program (95.8%) and
showed a willingness to pay an additional cost for the education (81.9%).
CONCLUSION: This study indicated that our newly developed education program would
become an effective component of asthma management in primary care clinics.
PMID- 28416958
TI - Keratinization of Lung Squamous Cell Carcinoma Is Associated with Poor Clinical
Outcome.
AB - BACKGROUND: Although the World Health Organization (WHO) classification of lung
squamous cell carcinoma (SCC) was revised in 2015, its clinical implications for
lung SCC subsets remain unclear. We investigated whether the morphologic
characteristics of lung SCC, including keratinization, were associated with
clinical parameters and clinical outcome of patients. METHODS: A total of 81
patients who underwent curative surgical resection of diagnosed lung SCC, were
enrolled in this study. Attributes such as keratinization, tumor budding, single
cell invasion, and nuclear size within the tumor, as well as immunohistochemistry
of Bcl-xL and pS6 expressions, were evaluated. RESULTS: The keratinizing and
nonkeratinizing subtypes did not differ with respect to age, sex, TNM stage, and
morphologic parameters such as nuclear diameter, tumor budding, and single cell
invasion at the tumor edge. Most patients with the keratinizing subtype (98.0%)
had a history of smoking, whereas the nonkeratinizing group had a relatively
higher proportion of never-smokers relative to the keratinizing group (24.0% vs.
2.0%; p=0.008, chi-square test). Expression of pS6 (a surrogate marker of
mammalian target of rapamycin complex 1 [mTORC1] signaling that regulates
keratinocyte differentiation), and Bcl-xL (a key anti-apoptotic molecule that may
inhibit keratinization), did not correlate significantly with the presence of
keratinization. Patients with the keratinizing subtype had a significantly
shorter overall survival (85.2 months vs. 135.7 months, p=0.010, log-rank test),
and a multivariate analysis showed that keratinization was an independent, poor
prognostic factor (hazard ratio, 2.389; 95% confidence interval, 1.090-5.233;
p=0.030). CONCLUSION: In lung SCC, keratinization is associated with a poor
prognosis, and might be associated with smoking.
PMID- 28416959
TI - Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant
Non-Small Cell Lung Cancer.
AB - BACKGROUND: Third-generation tyrosine kinase inhibitors of the epidermal growth
factor receptor (EGFR-TKIs) have proved efficacious in treating non-small cell
lung cancer (NSCLC) patients with acquired resistance resulting from the T790M
mutation. However, since almost 50% patients with the acquired resistance do not
harbor the T790M mutation, retreatment with first- or second-generation EGFR-TKIs
may be a more viable therapeutic option. Here, we identified positive response
predictors to retreatment, in patients who switched to a different EGFR-TKI,
following initial treatment failure. METHODS: This study retrospectively reviewed
the medical records of 42 NSCLC patients with EGFR mutations, whose cancers had
progressed following initial treatment with gefitinib or erlotinib, and who had
switched to a different first-generation EGFR-TKI during subsequent retreatment.
To identify high response rate predictors in the changed EGFR-TKI retreatment, we
analyzed the relationship between clinical and demographic parameters, and
positive clinical outcomes, following retreatment with EGFR-TKI. RESULTS:
Overall, 30 (71.4%) patients received gefitinib and 12 (28.6%) patients received
erlotinib as their first EGFR-TKI treatment. Following retreatment with a
different EGFR-TKI, the overall response and disease control rates were 21.4% and
64.3%, respectively. There was no significant association between their overall
responses. The median progression-free survival (PFS) after retreatment was 2.0
months. However, PFS was significantly longer in patients whose time to
progression was >=10 months following initial EGFR-TKI treatment, who had a
mutation of exon 19, or whose treatment interval was <90 days. CONCLUSION: In
patients with acquired resistance to initial EGFR-TKI therapy, switched EGFR-TKI
retreatment may be a salvage therapy for individuals possessing positive
retreatment response predictors.
PMID- 28416960
TI - Medical Thoracoscopy in Pleural Disease: Experience from a One-Center Study.
AB - BACKGROUND: Medical thoracoscopy (MT) is a minimally invasive, endoscopic
procedure for exploration of the pleural cavity under conscious sedation and
local anesthesia. MT has been performed at the Seoul National University Hospital
since February 2014. This paper summarizes the findings and outcomes of MT cases
at this hospital. METHODS: Patients who had undergone MT were enrolled in the
study. MT was performed by pulmonologists, using both rigid and semi-rigid
thoracoscopes. During the procedure, patients were under conscious sedation with
fentanyl and midazolam. Medical records were reviewed for clinical data. RESULTS:
From February 2014 to January 2016, 50 procedures (47 cases) were performed
(diagnostic MT, 26 cases; therapeutic MT, 24 cases). The median age of patients
was 66 years (59-73 years), and 38 patients (80.9%) were male. The median
procedure duration from initial incision to insertion of the chest tube was 37
minutes. The median doses of fentanyl and midazolam were 50 ug and 5 mg,
respectively. All procedures were performed without unexpected events. Of the 26
cases of pleural disease with an unknown cause, 19 were successfully diagnosed
using MT. Additionally, diagnostic MT provided clinically useful information in
the other six patients. Therapeutic MT was very effective for treatment of
malignant pleural effusion or empyema. The median number of days with chest tube
drainage was 6 (3 days for diagnostic MT and 8 days for therapeutic MT).
CONCLUSION: MT is a useful and necessary procedure for both diagnosis and
treatment of pleural diseases.
PMID- 28416961
TI - Predictive Factors of Methicillin-Resistant Staphylococcus aureus Infection in
Elderly Patients with Community-Onset Pneumonia.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a
severe and life-threatening disease in patients with community-onset (CO)
pneumonia. However, the current guidelines lack specificity for a screening test
for MRSA infection. METHODS: This study was retrospectively conducted in elderly
patients aged >=65 years, who had contracted CO-pneumonia during hospitalization
at the Jeju National University Hospital, between January 2012 and December 2014.
We analyzed the risk factors of MRSA in these patients and developed a scoring
system to predict MRSA infection. RESULTS: A total of 762 patients were enrolled
in this study, including 19 (2.4%) with MRSA infection. Healthcare-associated
pneumonia (HCAP) showed more frequent MRSA infection compared to community
acquired pneumonia (4.4% vs. 1.5%, respectively; p=0.016). In a multivariate
logistic regression analysis, admissions during the influenza season (odds ratio
[OR], 2.896; 95% confidence interval [CI], 1.022-8.202; p=0.045), chronic kidney
disease (OR, 3.555; 95% CI, 1.157-10.926; p=0.027), and intensive care unit
admission (OR, 3.385; 95% CI, 1.035-11.075; p=0.044) were identified as
predictive factors for MRSA infection. However, the presence of HCAP was not
significantly associated with MRSA infection (OR, 1.991; 95% CI, 0.720-5.505;
p=0.185). The scoring system consisted of three variables based on the
multivariate analysis, and showed moderately accurate diagnostic prediction (area
under curve, 0.790; 95% CI, 0.680-0.899; p<0.001). CONCLUSION: MRSA infection
would be considered in elderly CO-pneumonia patients, with three risk factors
identified herein. When managing elderly patients with pneumonia, clinicians
might keep in mind that these risk factors are associated with MRSA infection,
which may help in selecting appropriate antibiotics.
PMID- 28416962
TI - Cutaneous Leukocytoclastic Vasculitis with Gastrointestinal Involvement after
Anti-Tuberculosis Treatment.
PMID- 28416963
TI - Mitochondrial acclimation potential to ocean acidification and warming of Polar
cod (Boreogadus saida) and Atlantic cod (Gadus morhua).
AB - BACKGROUND: Ocean acidification and warming are happening fast in the Arctic but
little is known about the effects of ocean acidification and warming on the
physiological performance and survival of Arctic fish. RESULTS: In this study we
investigated the metabolic background of performance through analyses of cardiac
mitochondrial function in response to control and elevated water temperatures and
PCO2 of two gadoid fish species, Polar cod (Boreogadus saida), an endemic Arctic
species, and Atlantic cod (Gadus morhua), which is a temperate to cold eurytherm
and currently expanding into Arctic waters in the wake of ocean warming. We
studied their responses to the above-mentioned drivers and their acclimation
potential through analysing the cardiac mitochondrial function in permeabilised
cardiac muscle fibres after 4 months of incubation at different temperatures
(Polar cod: 0, 3, 6, 8 degrees C and Atlantic cod: 3, 8, 12, 16 degrees C),
combined with exposure to present (400MUatm) and year 2100 (1170MUatm) levels of
CO2. OXPHOS, proton leak and ATP production efficiency in Polar cod were similar
in the groups acclimated at 400MUatm and 1170MUatm of CO2, while incubation at 8
degrees C evoked increased proton leak resulting in decreased ATP production
efficiency and decreased Complex IV capacity. In contrast, OXPHOS of Atlantic cod
increased with temperature without compromising the ATP production efficiency,
whereas the combination of high temperature and high PCO2 depressed OXPHOS and
ATP production efficiency. CONCLUSIONS: Polar cod mitochondrial efficiency
decreased at 8 degrees C while Atlantic cod mitochondria were more resilient to
elevated temperature; however, this resilience was constrained by high PCO2. In
line with its lower habitat temperature and higher degree of stenothermy, Polar
cod has a lower acclimation potential to warming than Atlantic cod.
PMID- 28416964
TI - A nondestructive method to estimate the chlorophyll content of Arabidopsis
seedlings.
AB - BACKGROUND: Chlorophyll content decreases in plants under stress conditions,
therefore it is used commonly as an indicator of plant health. Arabidopsis
thaliana offers a convenient and fast way to test physiological phenotypes of
mutations and treatments. However, chlorophyll measurements with conventional
solvent extraction are not applicable to Arabidopsis leaves due to their small
size, especially when grown on culture dishes. RESULTS: We provide a
nondestructive method for chlorophyll measurement whereby the red, green and blue
(RGB) values of a color leaf image is used to estimate the chlorophyll content
from Arabidopsis leaves. The method accommodates different profiles of digital
cameras by incorporating the ColorChecker chart to make the digital negative
profiles, to adjust the white balance, and to calibrate the exposure rate
differences caused by the environment so that this method is applicable in any
environment. We chose an exponential function model to estimate chlorophyll
content from the RGB values, and fitted the model parameters with physical
measurements of chlorophyll contents. As proof of utility, this method was used
to estimate chlorophyll content of G protein mutants grown on different sugar to
nitrogen ratios. CONCLUSION: This method is a simple, fast, inexpensive, and
nondestructive estimation of chlorophyll content of Arabidopsis seedlings. This
method lead to the discovery that G proteins are important in sensing the C/N
balance to control chlorophyll content in Arabidopsis.
PMID- 28416965
TI - A crisis of protection and safe passage: violence experienced by
migrants/refugees travelling along the Western Balkan corridor to Northern
Europe.
AB - BACKGROUND: Pushed by ongoing conflicts and pulled by the desire for a better
life, over one million migrants/refugees transited Balkan countries and arrived
in Europe during 2015 and early 2016. To curb this influx, European countries
instituted restrictive migration policies often characterized by building of
razor-wire border fences and border closures. Among migrants/refugees who
received mental health care in Serbia while travelling through Balkan countries
to Northern Europe, we assessed the prevalence and patterns of violent events
experienced including physical trauma. METHODS: A mixed methods study among
migrants/refugees attending mobile mental health clinics run by Medecins sans
Frontieres (MSF) between July 2015 and June 2016, in Serbia - a main transit hub
to European countries. Clinics were conducted according to MSF guidelines by
experienced psychologists who were supported by cultural mediators. The main
outcome measures were violent events and associated physical trauma. RESULTS: Of
992 migrants/refugees attending MSF mental health clinics, the majority (72%)
were from Syria and Afghanistan and included vulnerable groups (14%) such as
unaccompanied minors and pregnant women. The most frequent mental health
symptoms/signs were anxiety (29%) and adjustment reactions (26%). Of the 992
migrants/refugees, 270 (27%) had experienced violent events during their journey.
Signs of physical trauma due to acts of violence were seen in 223(22%) of the 992
individuals, 144 (65%) being perpetrated by State authorities and involving women
(11%) and children (13%). Border closures along the Balkan route were associated
with a dramatic decrease in registered migrants/refugee arrivals in Serbia.
Conversely, among those that made it across the borders, an increasing linear
trend in reported violent events was observed at MSF mental health clinics (X2
for linear trend, P <0 . 001). Qualitative evidence corroborated with
quantitative findings. CONCLUSIONS: Nearly one-in-three migrants/refugees seen in
MSF clinics experienced violent events including physical trauma along their
journey. State authorities, including those in European countries were the
perpetrators in over half of such events which were associated with border
closures. There is "a crisis of protection and safe passage" which needs to
change towards one of respect for the principles of international human rights
and refugee law.
PMID- 28416966
TI - An overview of mental health care system in Kilifi, Kenya: results from an
initial assessment using the World Health Organization's Assessment Instrument
for Mental Health Systems.
AB - BACKGROUND: Little is known about the state of mental health systems in Kenya. In
2010, Kenya promulgated a new constitution, which devolved national government
and the national health system to 47 counties including Kilifi County. There is
need to provide evidence from mental health systems research to identify priority
areas in Kilifi's mental health system for informing county health sector
decision making. We conducted an initial assessment of state of mental health
systems in Kilifi County and documented resources, policy and legislation and
spectrum of mental, neurological and substance use disorders. METHODS: This was a
pilot study that used the brief version of the World Health Organization's
Assessment Instrument for Mental Health Systems Version 2.2 to collect data. Data
collection was based on the year 2014. RESULTS: Kilifi county has two public
psychiatric outpatient units that are part of general hospitals. There is no
standalone mental hospital in Kilifi. There are no inpatients or community based
facilities for people with mental health problems. Although the psychiatric
facilities in Kilifi have an essential drugs list, supply of drugs is erratic
with frequent shortages. There is no psychiatrist or psychologist in Kilifi with
only two psychiatric nurses for a population of approximately 1.2 million people.
Schizophrenia was the commonest reason for visiting outpatient facilities (47.1%)
while suicidal ideation was the least common (0.4%). Kenya's mental health
policy, which is being used by Kilifi County, is outdated and does not cater for
the current mental health needs of Kilifi. There is no specific legislation to
protect the rights of people with mental health problems. No budget exists
specifically for mental health care. There have been no efforts to integrate
mental health care into primary care in Kilifi, and there is no empirical
research work to evaluate its feasibility. CONCLUSION: There is an urgent need to
increase resources allocated for mental health in particular infrastructure and
human resource. Policy and legislations need to be established to protect the
rights of people with mental illnesses, and mental health should be integrated
with primary care to increase access to services.
PMID- 28416967
TI - Rescuing ethanol photosynthetic production of cyanobacteria in non-sterilized
outdoor cultivations with a bicarbonate-based pH-rising strategy.
AB - BACKGROUND: Ethanol photosynthetic production based on cyanobacteria cell
factories utilizing CO2 and solar energy provides an attractive solution for
sustainable production of green fuels. However, the scaling up processes of
cyanobacteria cell factories were usually threatened or even devastated by
biocontaminations, which restricted biomass or products accumulations of
cyanobacteria cells. Thus it is of great significance to develop reliable
biocontamination-controlling strategies for promoting ethanol photosynthetic
production in large scales. RESULTS: The scaling up process of a previously
developed Synechocystis strain Syn-HZ24 for ethanol synthesis was severely
inhibited and devastated by a specific contaminant, Pannonibacter phragmitetus,
which overcame the growths of cyanobacteria cells and completely consumed the
ethanol accumulation in the cultivation systems. Physiological analysis revealed
that growths and ethanol-consuming activities of the contaminant were sensitive
to alkaline conditions, while ethanol-synthesizing cyanobacteria strain Syn-HZ24
could tolerate alkaline pH conditions as high as 11.0, indicating that pH
increasing strategy might be a feasible approach for rescuing ethanol
photosynthetic production in outdoor cultivation systems. Thus, we designed and
evaluated a Bicarbonate-based Integrated Carbon Capture System (BICCS) derived pH
rising strategy to rescue the ethanol photosynthetic production in non-sterilized
conditions. In lab scale artificially simulated systems, pH values of BG11
culture medium were maintained around 11.0 by 180 mM NaHCO3 and air steam, under
which the infection of Pannonibacter phragmitetus was significantly restricted,
recovering ethanol production of Syn-HZ24 by about 80%. As for outdoor
cultivations, ethanol photosynthetic production of Syn-HZ24 was also successfully
rescued by the BICCS-derived pH-rising strategy, obtaining a final ethanol
concentration of 0.9 g/L after 10 days cultivation. CONCLUSIONS: In this work, a
novel product-consuming biocontamination pattern in cyanobacteria cultivations,
causing devastated ethanol photosynthetic production, was identified and
characterized. Physiological analysis of the essential ethanol-consuming
contaminant directed the design and application of a pH-rising strategy, which
effectively and selectively controlled the contamination and rescued ethanol
photosynthetic production. Our work demonstrated the importance of reliable
contamination control systems and strategies for large scale outdoor cultivations
of cyanobacteria, and provided an inspiring paradigm for targeting effective
solutions.
PMID- 28416968
TI - Safety and efficacy of resistive polymer versus forced air warming in total joint
surgery.
AB - BACKGROUND: Forced-air warming is used as a mechanism to prevent hypothermia and
adverse outcomes associated with hypothermia among patients undergoing surgery.
Patient safety in healthcare includes the use of devices and technology that
minimize potential adverse events to patients. The present study sought to
compare the capabilities of patient warming between two different devices that
use different mechanisms of warming: forced-air warming and non-air warming.
METHODS: One hundred twenty patients undergoing total hip or total knee
arthroplasty received patient warming via a forced warming device or non-air
warming fabric conductive material. The project was part of a quality improvement
initiative to identify warming devices effective in maintaining normothermic
patient core temperatures during orthopedic surgery. RESULTS: Forced-air warming
and non-air warming achieved similar results in maintaining the core temperature
of patients undergoing total knee or hip arthroplasty. No adverse events were
reported in either group. Operating room staff observed that the non-air warming
device was less noisy and appreciated the disposable covers that could be changed
after each surgical case. CONCLUSIONS: These findings demonstrate that
hypothermia is achieved by both forced-air and non-forced air warming devices
among total knee and hip arthroplasty patients. The potential for airflow
disruption is present with the forced-air warming device and does not exist with
the non-forced air device. The disruption of laminar airflow may be associated
with surgical site infections. The disposable covers used to protect the device
and patient have potential implications for surgical site infection. Quality
improvement efforts aimed to enhance patient safety should include the
implementation of healthcare equipment with the least known or suspected risk.
PMID- 28416969
TI - Repeatability and agreement of ultrasonography with computed tomography for
evaluating forefoot structure in the coronal plane.
AB - BACKGROUND: Forefoot structure is important to understand some foot problems such
as hallux valgus and metatarsalgia. Ultrasonography (US) is a highly portable,
noninvasive, low cost, and fast imaging method, especially when compared to
magnetic resonance imaging (MRI), computed tomography (CT), and radiography. As
the use of US for evaluating forefoot bony structure has not been validated,
except for the presence of synovitis, erosions and bursitis within the forefoot
in people with inflammatory arthritis, the purpose of this study was to determine
whether US is a reliable method for evaluating forefoot structure. METHODS: Sixty
feet (30 women, age = 40.1 +/- 11.8 years) were examined by US and CT to assess
agreement with CT and repeatability of US evaluation of the 2nd metatarsal head
height, length between the medial sesamoid bone and 5th metatarsal head,
transverse arch height, transverse arch index, sesamoid rotation angle, and area
under the transverse arch. The measurement data were evaluated for agreement with
CT using the intra-class correlation coefficient (ICC)3, 1, Pearson correlation
coefficient, and Bland-Altman plot, and with ICC1, 1 for repeatability. RESULTS:
The ICC3, 1 values of 0.78-0.89, Pearson correlation coefficient of 0.78-0.90,
and Bland-Altman plots showed almost perfect agreements between the US and CT
method for all parameters, except the area under the transverse arch (AUTA). The
ICC1, 1 also showed perfect agreements (0.84-0.92) between two sets of US
measurements in all parameters. CONCLUSIONS: The US evaluation of forefoot
structure in the coronal plane showed good agreement with CT and repeatability of
two ultrasonograms in adult women. This reliable evaluation method of forefoot
structure can contribute to a quick clinical assessment screening for risk
factors of foot problems such as hallux valgus and metatarsalgia. However,
because of some limitations such as a lack of inter-observer reliability, more
research is needed to validate US evaluation of forefoot structure. TRIAL
REGISTRATION: The current study (trial registration number: R0297) was approved
by the Ethical Committee for Human Experiments of Kyoto University
(http://www.ec.med.kyoto-u.ac.jp) on December 3, 2015. The first participant in
this study was enrolled on November 17, 2015 and retrospectively registered.
PMID- 28416970
TI - DNA methylation profiling in peripheral lung tissues of smokers and patients with
COPD.
AB - BACKGROUND: Epigenetics changes have been shown to be affected by cigarette
smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect
several cellular and pathophysiological processes, acute exacerbations, and
comorbidity in the lungs of patients with chronic obstructive pulmonary disease
(COPD). We sought to determine whether genome-wide lung DNA methylation profiles
of smokers and patients with COPD were significantly different from non-smokers.
We isolated DNA from parenchymal lung tissues of patients including eight
lifelong non-smokers, eight current smokers, and eight patients with COPD and
analyzed the samples using Illumina's Infinium HumanMethylation450 BeadChip.
RESULTS: Our data revealed that the differentially methylated genes were related
to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer,
and nNOS signaling in neurons), disease and disorders (organismal injury and
abnormalities, cancer, and respiratory disease), and molecular and cellular
functions (cell death and survival, cellular assembly and organization, cellular
function and maintenance) in patients with COPD. The genome-wide DNA methylation
analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1,
ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were
further validated by pyrosequencing. Pyrosequencing validation confirmed hyper
methylation in smokers and patients with COPD as compared to non-smokers.
However, we did not detect significant differences in DNA methylation for
TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes
observed in the genome-wide analysis. CONCLUSIONS: Our study suggests that DNA
methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as
epigenetic signatures in smokers and patients with COPD if the same is validated
in a larger cohort. Future studies are required to correlate DNA methylation
status with transcriptomics of selective genes identified in this study and
elucidate their role and involvement in the progression of COPD and its
exacerbations.
PMID- 28416971
TI - A multicenter study of the need of additional freezing for cryoballoon ablation
in patients with atrial fibrillation: The AD-Balloon study.
AB - BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone of catheter ablation
in patients with paroxysmal atrial fibrillation (PAF), and balloon-based ablation
has been recently performed worldwide. Ablation using the second-generation
cryoballoon (CB2) (Arctic Front AdvanceTM, Medtronic, MN, USA) is useful for PVI;
however, there is some debate concerning the optimal freezing time and number of
cycles after PVI is achieved. METHODS: The AD-Balloon study was designed as a
prospective, multicenter, randomized clinical trial to evaluate the optimal
strategy (freezing cycles) of CB2 ablation (UMIN Clinical Trials Registry
UMIN000020130). The main objective of this study is to investigate the need for
an additional freezing cycle after PVI in patients treated with CB2 ablation.
Patients will be randomly assigned in a 1:1 ratio to treatment with additional
freezing (AD group) or without additional freezing (non-AD group). In the AD
group, 3 min of additional freezing time will be applied in all pulmonary veins
after PVI is confirmed at the previous freezing cycle. In the non-AD group, no
additional freezing will be applied in all pulmonary veins after PVI is
confirmed. The primary endpoint of this study is the occurrence of atrial
tachyarrhythmias within a 1-year follow-up period. We will enroll 110 consecutive
patients with PAF. We will also investigate the usefulness of delayed-enhancement
magnetic resonance imaging to assess the ablation lesions caused by CB2 ablation.
RESULTS: The results of this study are currently under investigation. CONCLUSION:
The AD-Balloon study would assess the need for an additional freezing cycle after
PVI is achieved. Our findings may contribute to further improvement of the CB2
ablation procedure.
PMID- 28416972
TI - Crucial role of pulmonary vein firing as an initiator of typical atrial flutter:
Evidence of a close relationship between atrial fibrillation and typical atrial
flutter.
AB - BACKGROUND: Several studies reported that cavotricuspid isthmus-dependent atrial
flutter (typical AFL) frequently coexists with atrial fibrillation (AF); however,
the underlying mechanisms have not been fully investigated. This study aimed to
reveal the mechanisms of the initiation of typical AFL and the association
between typical AFL and AF. METHODS: Among 154 consecutive patients undergoing a
first catheter ablation of AF, we investigated the appearance and mechanism of
spontaneous initiation of typical AFL during catheter ablation. Then, we
retrospectively investigated 67 consecutive patients without a previous AF
episode who underwent typical AFL ablation. The occurrence and predictors of AF
after catheter ablation were evaluated. RESULTS: During AF ablation, spontaneous
initiation of typical AFL occurred during sinus rhythm in eight (5.2%) patients.
The initiations of typical AFL were pulmonary vein (PV) firings except in one
patient, in whom paroxysmal AF following superior vena cava firing initiated
reverse typical AFL after PV isolation. After typical AFL ablation, AF occurred
in 23 (34.3%) patients (mean follow up, 28.2+/-20.3 months). Kaplan-Meier
analysis showed the occurrence of AF after typical AFL ablation to be
significantly higher in the patients with a larger left atrial diameter over 40
mm (log-rank test, P=0.046). CONCLUSIONS: PV firing through AF played an
important role in initiating typical AFL. The occurrence of AF after typical AFL
ablation was high, and a dilated left atrium was associated with increased
occurrence of AF. These findings disclosed the close relationship between typical
AFL and AF, especially PV firing.
PMID- 28416973
TI - The utility of atrial pacing for identifying the electrical breakthrough sites
between the left atrium and pulmonary veins.
AB - BACKGROUND: Circumferential pulmonary vein (PV) isolation for atrial fibrillation
(AF) is occasionally difficult to achieve because electrical breakthrough sites
(EBSs) between the left atrium (LA) and PVs cannot be identified during ablation
especially in the carina regions. METHODS: The left PVs (Lt.PVs) of 60 AF
patients and the right PVs (Rt.PVs) of 37 patients undergoing PV isolation were
studied. When PV isolation was not achieved after the initial circumferential PV
isolation, atrial pacing was repeatedly performed from the distal coronary sinus
(CSd) and high right atrium (HRA), and the time interval from the stimulus to the
earliest PV potential (stimulus-PV interval) was measured using circular mapping
catheters at each PV until PV isolation was achieved. When PV isolation was
achieved via local Radiofrequency (RF) deliveries, those regions were diagnosed
as final EBSs. We classified the final EBSs into six segments for each PV
(anterior and posterior PV walls of the roof, carina, and bottom) and
investigated the relationship between the final EBSs and stimulus-PV intervals.
RESULTS: For Lt.PVs, the stimulus-PV intervals during CSd pacing were
significantly shorter than during HRA pacing at the Lt.PV anterior carina and
bottom (90+/-28 ms vs. 125+/-26 ms, P<0.001 and 84+/-20 ms vs. 148+/-24 ms,
P=0.028, respectively), but there was no significant difference in the Lt.PV roof
and any posterior segments. For Rt.PVs, the stimulus-PV interval from both pacing
sites exhibited no significant difference between either segment. CONCLUSIONS:
This pacing method may help to identify whether EBSs are located in the anterior
Lt.PVs. Improved recognition of EBSs through pacing from different sites would be
helpful for achieving PV isolation.
PMID- 28416974
TI - Major determinants for the selecting antithrombotic therapies in patients with
nonvalvular atrial fibrillation in Japan (JAPAF study).
AB - BACKGROUND: Oral anticoagulants (OACs) can help prevent stroke in patients with
nonvalvular atrial fibrillation (NVAF). The aim of this study was to characterize
the use of OACs other than direct thrombin inhibitors (DTIs) for NVAF. METHODS:
Patients with NVAF taking antithrombotics other than DTIs were enrolled in this
cross-sectional study. Patient demographics and medication history were
collected, and the patients were classified as taking antiplatelet monotherapy
(AP), anticoagulant monotherapy (AC), or combination therapy (AP+AC). OAC users
were also stratified as naive (N; initiated within 6 months), switcher (S;
switched within 6 months), or prevalent user (P; continued for >6 months).
RESULTS: A total of 3053 patients (AP, 216; AC, 2381; AP+AC, 456) from 268 sites
were enrolled from 2012 to 2013. Significant differences were observed in CHADS2
scores (AP/AC/AP+AC: 2.0/2.1/2.7, P<0.0001), angina complications (20.1/8.6/32.1,
P<0.0001), myocardial infarction (5.1/2.8/18.1, P<0.0001), prothrombin time
international normalized ratio (PT-INR) (-/2.00/1.94, P=0.0350), and others.
There were 2831 OAC users (N, 328; S, 213; P, 2290). Significant differences were
observed in history of bleeding (N/S/P: 2.4/9.4/4.5, P<0.001), PT-INR
(1.83/2.01/2.00, P<0.0001), and others. CONCLUSIONS: Patients taking AP+AC had
higher CHADS2 scores than those taking an AP or AC alone. Additionally, the
combination therapy (AP+AC) was preferred in patients with cardiovascular
comorbidity. Changes in AC regimens were not influenced by CHADS2 scores or
complications but influenced by history of bleeding. These characteristics were
thus identified as major factors affecting the selection of antithrombotic
regimens other than DTIs in patients with NVAF.
PMID- 28416975
TI - Effectiveness and safety of dabigatran versus warfarin in "real-world" Japanese
patients with atrial fibrillation: A single-center observational study.
AB - BACKGROUND: In "real-world" practice, anticoagulant therapy is indicated for
patients whose clinical profiles are not addressed in randomized clinical trials.
We assessed the effectiveness and safety of dabigatran versus warfarin in "real
world" Japanese patients with non-valvular atrial fibrillation (NVAF). METHODS:
Among 613 NVAF patients who initiated dabigatran or warfarin therapy during the
period between 2011 and 2013, 362 patients were included in the study after
propensity score adjustment. The median follow-up period was 1.3 years. The
effectiveness and safety outcomes were thromboembolism and major bleeding,
respectively. RESULTS: The propensity-matched hazard ratios of thromboembolism
and major bleeding with dabigatran were 1.03 (95% CI: 0.12-8.04, p=0.971) and
0.15 (95% CI: 0.01-0.90, p=0.037), respectively. CONCLUSIONS: The ability of
dabigatran to prevent thromboembolism is comparable to that of warfarin; however,
the major bleeding rate is lower with dabigatran in "real-world" NVAF patients.
PMID- 28416977
TI - Trends in physiological coagulation factors in Japanese patients receiving novel
oral anticoagulants.
AB - BACKGROUND: Little is known about physiological anticoagulation effects via
antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral
anticoagulants (NOACs). METHODS: We evaluated 120 consecutive patients with non
valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided
into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40)
or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with
NOAC groups for age, sex and type of AF during the same time period. Blood
samples were obtained in pretreatment, trough and peak phases to measure the
activity of physiological coagulation inhibitors, including AT III and PC/PS or
thrombus formation markers such as D-dimer and thrombin-antithrombin complex
(TAT). RESULTS: D-dimer, TAT and AT III values for the NOAC groups were
equivalent in the peak and trough phases. PC/PS activity in both phases was
equally maintained in the pretreatment phase in the NOAC groups, while the
activity in the WG was significantly suppressed in steady state. Moreover, no
differences in trends for PC/PS activity were observed among NOAC groups.
CONCLUSIONS: PC/PS activity was constant in both peak and trough phases in the
patients on NOACs compared with activity of those on warfarin. In addition, there
was no difference in the findings among NOACs.
PMID- 28416976
TI - Rationale and design of ASSAF-K (A study of the safety and efficacy of
anticoagulant therapy in the treatment of atrial fibrillation in Kanagawa).
AB - BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent cardiac
arrhythmias associated with substantially increased risks of ischemic stroke and
thromboembolism. Oral anticoagulants (OACs) are the cornerstone of AF management
and effectively prevent AF-related stroke. As new non-vitamin K antagonist OACs
(NOACs) have become available, the landscape of stroke prevention in AF has
changed. However, there are considerable gaps between daily clinical practice and
current guideline-based recommendations for anticoagulant therapy in Japan.
Consequently, little is known about the real-world setting and the current use of
NOACs, especially by practitioners in Japan. METHODS: We conducted a prospective,
observational study in 3847 patients with AF who were enrolled in clinics and
hospitals located in Kanagawa Prefecture from September 2013 through March 2015.
The participating centers included practitioners (small clinics), medium-sized
hospitals, and university hospitals. The primary endpoints were epidemiologic
characteristics, status of treatment with anticoagulants and antiplatelet agents,
outcomes, and adverse events, including cerebrovascular disease, bleeding, and
death. RESULTS: The mean CHADS2 score was 1.81+/-1.27, the mean CHADS2-Vasc score
was 3.02+/-1.58, and the mean HAS-BLED score was 2.23+/-1.06, respectively. The
usage rate of warfarin was 44.2% overall, and the usage rate of NOACs was 33.5%.
CONCLUSIONS: The results of the study are expected to serve as the basis for
providing clinical practice guidance to healthcare institutions in Japan, with
the ultimate goals of better characterizing the appropriate use of OACs and
providing clinical decision support to physicians to facilitate the design of
appropriate therapeutic strategies and the selection of anticoagulants for the
management of AF.
PMID- 28416978
TI - Atrial electromechanical delay in patients undergoing heart transplantation.
AB - BACKGROUND: We aimed to assess atrial electromechanical delay (AEMD) in patients
who had undergone heart transplantation. METHODS: A total of 32 patients who
underwent biatrial anastomosis heart transplantation (24 men, 8 women; mean age:
42+/-11 years) and 30 healthy volunteers (20 men, 10 women; mean age: 36+/-13
years) were included in the study. Atrial electromechanical coupling (PA), intra
AEMD, and inter-AEMD were measured. RESULTS: PA lateral (68+/-7 vs. 51+/-11 ms,
p<0.01), PA septal (50+/-5 vs. 42+/-8 ms, p< 0.01) and PA tricuspid (39+/-6 vs.
36+/-9 ms, p<0.01), inter-AEMD (PA lateral-PA tricuspid) (27+/-7 vs. 10+/-4 ms,
p<0.01), left intra-AEMD (PA lateral-PA septal) (18+/-7 vs. 10+/-4 ms, p<0.01),
right intra-AEMD (PA septal-PA tricuspid) (13+/-5 vs. 5+/-3 ms, p<0.01) values
were higher in patients who underwent heart transplantation than in a control
population. CONCLUSION: Inter-AEMD and intra-AEMD were prolonged in patients who
underwent heart transplantation as compared to a control population. This may
explain the increased atrial fibrillation and other atrial arrhythmia incidences
associated with the biatrial anastomosis heart transplantation technique and may
contribute to the treatment of atrial fibrillation in this special patient group.
PMID- 28416979
TI - Comparison of hemodynamic effects of biventricular versus left ventricular only
pacing in patients receiving cardiac resynchronization therapy: A before-after
clinical trial.
AB - BACKGROUND: Biventricular (BiV) pacing is the most common mode of delivering
cardiac resynchronization therapy (CRT). However, initial clinical studies have
indicated that left ventricular (LV) pacing is not inferior to BiV pacing. This
study was conducted to address whether LV only pacing can provide the same
hemodynamic response as BiV pacing. METHODS: This before-after clinical trial was
conducted at Ekbatan Hospital, from July 2012 to November 2014. Patients with a
LV ejection fraction <=35% and a QRS duration >=0.12 s who had a standard
indication for ventricular pacing were enrolled. The CRT devices of all patients
had already been set for BiV pacing. Therefore, their CRT devices were set for LV
only pacing for 3 months. The hemodynamic status of the patients was assessed by
echocardiography before setting the CRT device to LV only pacing (as a control)
and 3 months after (as an intervention). RESULTS: There was no statistically
significant difference between the effect of BiV pacing and LV only pacing on the
hemodynamic responses including LV ejection fraction, LV end diastolic and
systolic volume, and velocity time integral of the aortic valve. Moreover, no
significant difference was seen between men and women either. CONCLUSIONS: LV
only pacing is not inferior to BiV pacing, and the hemodynamic response was
similar in the two groups. However, the LV mode has a number of advantages over
the BiV mode. More evidence, based on large clinical trials, is needed to confirm
our results.
PMID- 28416980
TI - Comparison of the measured pre-ejection periods and left ventricular ejection
times between echocardiography and impedance cardiography for optimizing cardiac
resynchronization therapy.
AB - BACKGROUND: The pre-ejection period (PEP) and left ventricular ejection time
(LVET) are easily measured by impedance cardiography (ICG). We hypothesized that
the PEP/LVET measured by ICG would correlate with that measured by
echocardiography, and that PEP/LVET measured by ICG would be useful for cardiac
resynchronization therapy (CRT) optimization. METHODS: Newly CRT implanted
patients were optimized by echocardiography. The PEP/LVET was measured by
echocardiography and ICG in two different settings: optimized setting and right
ventricle (RV)-only pacing. RESULTS: The PEP/LVET was significantly decreased in
the optimized setting compared with that in RV-only pacing (0.62+/-0.13 vs 0.75+/
0.16, p<0.05). The PEP/LVET values calculated by ICG and echocardiography were
positively correlated (r=0.553, p=0.003). CONCLUSION: ICG was useful for the
optimization of CRT.
PMID- 28416981
TI - Relationship between right and left ventricular function in candidates for
implantable cardioverter defibrillator with low left ventricular ejection
fraction.
AB - BACKGROUND: Indications for the primary prevention of sudden death using an
implantable cardioverter defibrillator (ICD) are based predominantly on left
ventricular ejection fraction (LVEF). However, right ventricular ejection
fraction (RVEF) is also a known prognostic factor in a variety of structural
heart diseases that predispose to sudden cardiac death. We sought to investigate
the relationship between right and left ventricular parameters (function and
volume) measured by cardiovascular magnetic resonance (CMR) among a broad
spectrum of patients considered for an ICD. METHODS: In this retrospective,
single tertiary-care center study, consecutive patients considered for ICD
implantation who were referred for LVEF assessment by CMR were included. Right
and left ventricular function and volumes were measured. RESULTS: In total, 102
patients (age 62+/-14 years; 23% women) had a mean LVEF of 28+/-11% and RVEF of
44+/-12%. The left ventricular and right ventricular end diastolic volume index
was 140+/-42 mL/m2 and 81+/-27 mL/m2, respectively. Eighty-six (84%) patients had
a LVEF <35%, and 63 (62%) patients had right ventricular systolic dysfunction.
Although there was a significant and moderate correlation between LVEF and RVEF
(r=0.40, p<0.001), 32 of 86 patients (37%) with LVEF <35% had preserved RVEF,
while 9 of 16 patients (56%) with LVEF >=35% had right ventricular systolic
dysfunction (Kappa=0.041). CONCLUSIONS: Among patients being considered for an
ICD, there is a positive but moderate correlation between LVEF and RVEF. A
considerable proportion of patients who qualify for an ICD based on low LVEF have
preserved RVEF, and vice versa.
PMID- 28416982
TI - Automatic atrial capture device control in real-life practice: A multicenter
experience.
AB - BACKGROUND: Device-based fully automatic pacing capture detection is useful in
clinical practice and important in the era of remote care management. The main
objective of this study was to verify the effectiveness of the new ACAP
Confirm(r) algorithm in managing atrial capture in the medium term in comparison
with early post-implantation testing. METHODS: Data were collected from 318
patients (66% male; mean age, 73+/-10 years); 237 of these patients underwent
device implantation and 81 box changes in 31 Italian hospitals. Atrial threshold
measurements were taken manually and automatically at different pulse widths
before discharge and during follow-up (7+/-2 months) examination. RESULTS: The
algorithm worked as expected in 73% of cases, considering all performed tests.
The success rate was 65% and 88% pre-discharge and during follow-up examination
(p<0.001), respectively, in patients who had undergone implantation. We did not
detect any difference in the performance of the algorithm as a result of the type
of atrial lead used. The success rate was 70% during pre-discharge testing in
patients undergoing device replacement. Considering all examination types, manual
and automatic measurements yielded threshold values of 1.07+/-0.47 V and 1.03+/
0.47 V at 0.2-ms pulse duration (p=0.37); 0.66+/-0.37 V and 0.67+/-0.36 V at 0.4
ms (p=0.42); and 0.5+/-0.28 V and 0.5+/-0.29 V at 1 ms (p=0.32). CONCLUSIONS: The
results show that the algorithm works before discharge, and its reliability
increases over the medium term. The algorithm also proved accurate in detecting
the atrial threshold automatically. The possibility of activating it does not
seem to be influenced by the lead type used, but by the time from implantation.
PMID- 28416984
TI - The inferior displacement of the His bundle and fast pathway in a patient with
common type atrioventricular nodal tachycardia: Three-dimensional computed
tomography analysis.
AB - A 66-year-old woman with palpitations was referred to our center for catheter
ablation due to drug-refractory, common type atrioventricular nodal tachycardia
(AVNRT). A selective slow pathway ablation was attempted. A fast junctional
rhythm with transient ventriculoatrial block followed by transient prolongation
of the A-H interval occurred immediately after the radiofrequency (RF)
application at the coronary sinus ostium (CSOS) level. To assess the location of
the fast pathway and His bundle, we sought to visualize the anatomy of the
triangle of Koch (TOK) by three-dimensional computed tomography (CT).
PMID- 28416983
TI - Local conduction during acute myocardial infarction in rats: Interplay between
central sympathetic activation and endothelin.
AB - We investigated the effects of autonomic dysfunction and endothelin on local
conduction and arrhythmogenesis during myocardial infarction. We recorded
ventricular tachyarrhythmias, monophasic action potentials, and activation
sequences in wild-type and ETB-deficient rats displaying high endothelin levels.
Central sympathetic inputs were examined after clonidine administration.
Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild
type rats, respectively. The right ventricular activation delay increased in
clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats.
The left ventricular voltage rise decreased in all groups, whereas the activation
delay increased mainly in clonidine-treated ETB-deficient rats. Central
sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis.
Ischemia alters excitability, whereas endothelin impairs local conduction, an
action partly counterbalanced by central sympathetic activity.
PMID- 28416985
TI - Successful pacemaker lead extraction involving an ossified thrombus: A case
report.
AB - A 41-year-old woman who had been fitted with a pacemaker 18 years prior presented
for lead extraction because of device infection. First, we tried laser sheath.
However, it cannot cross the binding in the innominate vein. Then we switched to
the rotating mechanical sheath. Although it crunched through binding tissue, the
progress halted. We removed the sheath and found pieces of calcified tissue in
the sheath lumen. After removing the calcified tissue, both leads were extracted
using the laser sheath, without complications. The pathological examination
revealed a diagnosis of ossified thrombus. Venous thromboses associated with
implanted leads can ossify with time, causing difficulties in the extraction of
long-standing intravascular leads.
PMID- 28416986
TI - Two cases of inappropriate implantable cardioverter-defibrillator therapies due
to T wave oversensing induced by body twisting.
AB - T wave oversensing (TWOS) is a common cause of inappropriate implantable
cardioverter-defibrillator (ICD) therapies. Various algorithms to avoid
inappropriate ICD therapy are available; however, they are not helpful to avoid
TWOS. Although the reproduction of TWOS is useful to resolve the problem of TWOS,
it is sometimes difficult to reproduce TWOS. We report two cases of inappropriate
ICD therapy due to TWOS, which were induced only by body twisting. We can
successfully manage the device based on the evidence of reproduced TWOS.
PMID- 28416987
TI - Importance of exercise testing shortly after subcutaneous implantable
cardioverter-defibrillator implantation in patients with Brugada syndrome - The
first case of associated inappropriate shock in Japan.
AB - We report the case of a 51-year-old patient with Brugada syndrome (BrS) who
experienced inappropriate shock due to T-wave oversensing (TWOS) during exercise
when the optimal sensing vector was selected based on the automatic analysis by a
subcutaneous implantable cardioverter-defibrillator (S-ICD). After selecting
another vector during exercise testing, TWOS did not re-occur. Selection of
appropriate sensing vector based on analyses under various conditions, including
during exercise after S-ICD implantation, should be considered for patients with
BrS.
PMID- 28416988
TI - Loss of atrial pacing in a patient with a dual-chamber permanent pacemaker: What
is the mechanism?
PMID- 28416989
TI - Immediate Breast Reconstruction of a Nipple Areolar Lumpectomy Defect With the L
Flap Skin Paddle Breast Reduction Design and Contralateral Reduction Mammoplasty
Symmetry Procedure: Optimizing the Oncoplastic Surgery Multispecialty Approach.
AB - Objective: We describe a modification of the inferior pedicle reduction
mammoplasty for oncoplastic reconstruction of a central tumor defect. Our
technique involved a deepithelialized L-shaped medial inferior based flap with
removal of lateral breast tissue after central lumpectomy with a contralateral
Wise-pattern mastopexy with inferior pedicle for symmetry. This technique is
ideal for patients with large, ptotic breasts that desire breast conservation
with immediate reconstruction. Methods: A 47-year-old woman with size 38 DD
breasts presented with a palpable 2-cm subareolar mass of the left breast.
Surgical oncology performed a left lumpectomy with nipple-areola complex excision
and a sentinel lymph node biopsy. Immediate left breast reconstruction was
performed with an inferior pedicle island flap. An additional 30 g of breast
tissue was excised laterally for contour, and the neo-nipple-areola complex was
rotated into the defect to facilitate inverted-T closure. A standard Wise-pattern
mastopexy with inferior pedicle was then performed on the right breast and an
additional 205 g of tissue was removed for symmetry. Results: The patient showed
excellent symmetry at the conclusion of the procedure. Final pathology
demonstrated complete excision of the tumor with negative margins. The entire neo
nipple-areola complex skin island was viable postoperatively. Conclusions:
Immediate reconstruction of a nipple-areola complex lumpectomy defect with a L
shaped medial inferior based skin paddle flap and contralateral reduction
mammoplasty provides an excellent cosmetic outcome in patients with large, ptotic
breasts and central defects following oncologic tumor resection.
PMID- 28416990
TI - Medications for osteoporotic pain.
PMID- 28416991
TI - Can denosumab be a substitute, competitor, or complement to bisphosphonates?
AB - Osteoblasts, originating from mesenchymal cells, make the receptor activator of
the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to
control differentiation of activated osteoclasts, originating from hematopoietic
stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature
osteoclasts, bone resorption increases. On the contrary, when OPG binds to the
RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy
receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL
resulting in inhibition of osteoclastogenesis and reduction of bone resorption.
Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of
resorption performed by activated osteoclasts, are still the drugs of choice to
prevent and treat osteoporosis. The merits of denosumab are reversibility
targeting the RANKL, lack of adverse gastrointestinal events, improved adherence
due to convenient biannual subcutaneous administration, and potential use with
impaired renal function. The known adverse reactions are musculoskeletal pain,
increased infections with adverse dermatologic reactions, osteonecrosis of the
jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of
denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3
days, with maximum reduction occurring by 1 month. The mean time to maximum
denosumab concentration is 10 days with a mean half-life of 25.4 days. In
conclusion, the convenient biannual subcutaneous administration of 60 mg of
denosumab can be considered as a first-line treatment for osteoporosis in cases
of low compliance with BPs due to gastrointestinal trouble and impaired renal
function.
PMID- 28416992
TI - Sphenopalatine ganglion block for relieving postdural puncture headache:
technique and mechanism of action of block with a narrative review of efficacy.
AB - The sphenopalatine ganglion (SPG) is a parasympathetic ganglion, located in the
pterygopalatine fossa. The SPG block has been used for a long time for treating
headaches of varying etiologies. For anesthesiologists, treating postdural
puncture headaches (PDPH) has always been challenging. The epidural block patch
(EBP) was the only option until researchers explored the role of the SPG block as
a relatively simple and effective way to treat PDPH. Also, since the existing
evidence proving the efficacy of the SPG block in PDPH is scarce, the block
cannot be offered to all patients. EBP can be still considered if an SPG block is
not able to alleviate pain due to PDPH.
PMID- 28416993
TI - Antinociceptive effect of intrathecal sec-O-glucosylhamaudol on the formalin
induced pain in rats.
AB - BACKGROUND: The root of Peucedanum japonicum Thunb., a perennial herb found in
Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous
study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was
performed to examine the antinociceptive effect of intrathecal SOG in the
formalin test. METHODS: Male Sprague-Dawley rats were implanted with an
intrathecal catheter. Rats were randomly treated with a vehicle and SOG (10 ug,
30 ug, 60 ug, and 100 ug) before formalin injection. Five percent formalin was
injected into the hind-paw, and a biphasic reaction followed, consisting of
flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone
was injected 10 min before administration of SOG 100 ug to evaluate the
involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values
were calculated. RESULTS: Intrathecal SOG showed a significant reduction of the
flinching responses at both phases in a dose-dependent manner. Significant
effects were showed from the dose of 30 ug and maximum effects were achieved at a
dose of 100 ug in both phases. The ED50 value (95% confidence intervals) of
intrathecal SOG was 30.3 (25.8-35.5) ug during phase 1, and 48.0 (41.4-55.7)
during phase 2. The antinociceptive effects of SOG (100 ug) were significantly
reverted at both phases of the formalin test by naloxone. CONCLUSIONS: These
results demonstrate that intrathecal SOG has a very strong antinociceptive effect
in the formalin test and it seems the effect is related to an opioid receptor.
PMID- 28416994
TI - The radiation safety education and the pain physicians' efforts to reduce
radiation exposure.
AB - BACKGROUND: C-arm fluoroscopy equipment is important for interventional pain
management and can cause radiation injury to physicians and patients. We compared
radiation safety education and efforts to reduce the radiation exposure of pain
specialists. METHODS: A survey of 49 pain specialists was conducted anonymously
in 2016. The questionnaire had 16 questions. That questionnaire was about
radiation safety knowledge and efforts to reduce exposure. We investigated the
correlation between radiation safety education and efforts of radiation
protection. We compared the results from 2016 and a published survey from 2011.
RESULTS: According to the 2016 survey, all respondents used C-arm fluoroscopy in
pain interventions. Nineteen respondents (39%) had received radiation safety
education. Physicians had insufficient knowledge about radiation safety. When the
radiation safety education group and the non-education group are compared, there
was no significant difference in efforts to reduce radiation exposure and
radiation safety knowledge. When the 2011 and 2016 surveys were compared, the use
of low dose mode (P = 0.000) and pulsed mode had increased significantly (P =
0.001). The number checking for damage to radiation protective garments (P =
0.000) and use of the dosimeter had also increased significantly (P = 0.009). But
there was no significant difference in other efforts to reduce radiation
exposure. CONCLUSIONS: Pain physicians seem to lack knowledge of radiation safety
and the number of physicians receiving radiation safety education is low.
According to this study, education does not lead to practice. Therefore, pain
physicians should receive regular radiation safety education and the education
should be mandatory.
PMID- 28416995
TI - Sufficient explanation of management affects patient satisfaction and the
practice of post-treatment management in spinal pain, a multicenter study of 1007
patients.
AB - BACKGROUND: Spinal pain is most common symptom in pain clinic. In most cases,
before the treatment of spinal pain, physician explains the patient's disease and
treatment. We investigated patient's satisfaction and physician's explanation
related to treatments in spinal pain patients by questionnaires. METHODS:
Anonymous questionnaires about physician's explanation and patient's satisfaction
in each treatment and post-treatment management were asked to individuals
suffering from spinal pain. Patients who have spinal pain were participated in
our survey of nationwide university hospitals in Korea. The relationships between
patient's satisfaction and other factors were analyzed. RESULTS: Between June
2016 and August 2016, 1007 patients in 37 university hospitals completed the
questionnaire. In the statistical analysis, patient's satisfaction of treatment
increased when pain severity was low or received sufficient preceding explanation
about nerve block and medication (P < 0.01). Sufficient explanation increased
patient's necessity of a post-treatment management and patients' performance rate
of post-treatment management (P < 0.01). CONCLUSIONS: These results show that
sufficient explanation increased patients' satisfaction after nerve block and
medication. Sufficient explanation also increased the practice of patients' post
treatment management.
PMID- 28416996
TI - The relationship between the development of musculoskeletal disorders, body mass
index, and academic stress in Bahraini University students.
AB - BACKGROUND: There are many mechanisms in which stress can lead to weight gain
thus high a BMI. The endocrine and inflammatory pathway can directly increase
abdominal adiposity. Another way in which stress leads to weight gain is through
changes in health behaviors. The study aimed to investigate the prevalence of
musculoskeletal disorders (MSDs) among healthy students of Ahlia University, and
to determine the relationship between the development of MSDs and academic
stressors and body mass index. METHODS: Self-administered questionnaires were
distributed to 94 students aged 18-26 years who were enrolled at various Ahlia
University colleges and met other inclusion criteria. The students responded to
the standardized Nordic musculoskeletal questionnaire and the modified College
Student Stress Inventory regarding musculoskeletal symptoms and academic
stressors. Height and weight measurements were also obtained to determine body
mass index. RESULTS: A total of 77.66% reported MSDs in one or more body part,
with the prevalence being higher among women than among men. The 7-day prevalence
of MSDs severe enough to interfere with activities of daily living was 60.64%,
and 44.68% by female and male students, respectively. There was a significant
relationship between academic stress and MSDs in the neck, shoulders, lower back,
and hips, while the relationship between MSDs, and body mass index, academic
stress, and grade point average was not significant. CONCLUSIONS: The prevalence
of MSDs among Ahlia University students was found to be high. Apart from the
positive correlation between academic stress and MSDs in certain body parts,
other correlations were not significant.
PMID- 28416997
TI - Comparison of intrathecal versus intra-articular dexmedetomidine as an adjuvant
to bupivacaine on postoperative pain following knee arthroscopy: a randomized
clinical trial.
AB - BACKGROUND: Postoperative pain is a common, distressing symptom following
arthroscopic knee surgery. The aim of this study was to compare the potential
analgesic effect of dexmedetomidine after intrathecal versus intra-articular
administration following arthroscopic knee surgery. METHODS: Ninety patients
undergoing unilateral elective arthroscopic knee surgery were randomly assigned
into three groups in a double-blind placebo controlled study. The intrathecal
dexmedetomidine group (IT) received an intrathecal block with intrathecal
dexmedetomidine, the intra-articular group (IA) received an intrathecal block and
intra-articular dexmedetomidine, and the control group received an intrathecal
block and intra-articular saline. The primary outcome of our study was
postoperative pain as assessed by the visual analogue scale of pain (VAS).
Secondary outcomes included the effect of dexmedetomidine on total postoperative
analgesic use and time to the first analgesic request, hemodynamics, sedation,
postoperative nausea and vomiting, patient satisfaction, and postoperative C
reactive protein (CRP) levels. RESULTS: Dexmedetomidine administration decreased
pain scores for 4 h in both the intrathecal and intra-articular groups, compared
to only 2 h in the control patient group. Furthermore, there was a significant
reduction in pain scores for 6 h in the intra-articular group. The time to the
first postoperative analgesia request was longer in the intra-articular group
compared to the intrathecal and control groups. The total meperidine requirement
was significantly lower in the intra-articular and intrathecal groups than in the
control group. CONCLUSIONS: Both intrathecal and intra-articular dexmedetomidine
enhanced postoperative analgesia after arthroscopic knee surgery. Less total
meperidine was required with intra-articular administration to extend
postoperative analgesia to 6 h with hemodynamic stability.
PMID- 28416998
TI - Prevalence and trends of pain associated with chronic diseases and personal out
of-pocket medical expenditures in Korea.
AB - BACKGROUND: There have been few studies about pain using a big data. The purpose
of this study was to identify the prevalence of pain, and trends of pain
associated with chronic diseases and personal out-of-pocket medical expenditures
over time. METHODS: Subjects were 58,151 individuals, using the Korea Health
Panel from 2009 to 2013. Chi-square and multinomial logistic regression were
conducted to identify the prevalence and odds ratios (ORs) of pain. Repeated
measures ANOVA was used to find the trend over these 5 years. RESULTS: Prevalence
of mild and severe pain was 28.1% and 1.7% respectively. The ORs of mild and
severe pain were 1.6 and 1.4 in females compared with males. From 2009 to 2013,
numbers of chronic diseases producing mild pain were 2.1, 2.4, 2.8, 2.9, and 3.1
and those producing severe pain were 3.0, 3.4, 3.9, 4.2, and 4.4, respectively.
After applying the average South Korean inflation rate by year over 5 years, the
annual, personal out-of-pocket medical expenditures (unit: ?1,000) for mild pain
were 322, 349, 379, 420, and 461, and those for severe pain were 331, 399, 504,
546, and 569, respectively (P < 0.0001). CONCLUSIONS: The pain prevalence was
29.8%. The numbers of chronic diseases and the personal out-of-pocket medical
expenditures revealed increasing trends annually, especially in those with pain.
Therefore, to eliminate and alleviate the pain, there needs to be further study
for developing a systemic approach.
PMID- 28416999
TI - Bilateral maxillary and mandibular buccal exostosis: a self reported case and a
proposal to include buccal exostosis under miscellaneous disorders of revised
working classification of the psychosomatic disorders pertaining to dental
practice.
PMID- 28417000
TI - hackseq: Catalyzing collaboration between biological and computational scientists
via hackathon.
AB - hackseq ( http://www.hackseq.com) was a genomics hackathon with the aim of
bringing together a diverse set of biological and computational scientists to
work on collaborative bioinformatics projects. In October 2016, 66 participants
from nine nations came together for three days for hackseq and collaborated on
nine projects ranging from data visualization to algorithm development. The
response from participants was overwhelmingly positive with 100% (n = 54) of
survey respondents saying they would like to participate in future hackathons. We
detail key steps for others interested in organizing a successful hackathon and
report excerpts from each project.
PMID- 28417001
TI - Minimally invasive esophagectomy for esophageal cancer according to the location
of the tumor: Experience of 251 patients.
AB - BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly used for the
treatment of esophageal cancer. However, the ideal approach of MIE is not yet
standardized. We explore the ideal approach of MIE according to the location of
the tumor and compare the clinical outcomes between patients with cancer arising
in the upper third of the esophagus and those with tumors involving the middle
and lower third of the esophagus. METHODS: We included patients with esophageal
carcinoma and had clear indications for MIE. For cancer arising in the upper
third of the esophagus, MIE McKeown approach was performed. For tumors involving
the middle and lower third of the esophagus, MIE Ivor Lewis approach was adopted.
RESULTS: Of the 251 patients included in this analysis, 200 patients underwent
Ivor-Lewis MIE and 51 patients underwent McKeown MIE. The incidence of
anastomotic leak, anastomotic stenosis and recurrent laryngeal nerve injury was
significantly higher in the McKeown MIE group than that in the Ivor Lewis MIE
group. The 30-day postoperative mortality rate was 1.2% (n = 1) in the McKeown
MIE group. Lymph nodes harvested were significantly more in the MIE-McKeown group
than in Ivor Lewis MIE group (P < 0.05). The median follow-up period was 15
months (1-25 months) and the overall survival rate at 1 year stratified by
pathologic stage at esophagectomy was 95.9% (stage 1), 83.8% (stage II), 73.4%
(stage III). CONCLUSIONS: MIE for esophageal cancer according to the location and
clinical stage of the tumor will decrease all postoperative complications and may
yield the greatest benefit from surgery.
PMID- 28417002
TI - Motivation to change, coping, and self-esteem in adolescent anorexia nervosa: a
validation study of the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ).
AB - BACKGROUND: Understanding motivation to change is a key issue in both the
assessment and the treatment of eating disorders. Therefore, sound instruments
assessing this construct are of great help to clinicians. Accordingly, the
present study analysed the psychometric properties of the Anorexia Nervosa Stages
of Change Questionnaire (ANSOCQ), including its relation to coping style and self
esteem. METHODS: N = 92 adolescents referred to an eating disorders outpatient
clinic meeting criteria for anorexia nervosa gave written informed consent to
participate in this study and completed the ANSOCQ, the Eating Disorder
Inventory, the Eating Attitudes Test, the Body Image Questionnaire, two
questionnaires measuring Self-Related Cognitions and the Coping Across Situations
Questionnaire. After a treatment period of nine months, clinical anorexia nervosa
diagnosis and the body mass index were re-assessed. In addition to exploratory
factor analysis, correlational analysis was used to test for the convergent
validity of the ANSOCQ and logistic regression analysis was used to test its
predictive validity. RESULTS: The ANSOCQ had good psychometric properties. Factor
analysis yielded two meaningful factors labelled as 'weight gain and control' and
'attitudes and feelings'. Internal consistencies of the two factors amounted to
Cronbach's alpha = .87 and .76, respectively. Significant correlations with other
scales measuring eating disorder psychopathology were indicative of meaningful
construct validity. Higher motivation to change was related to higher self-esteem
and a more active coping style. Higher (positive) ANSOCQ total scores predicted
remission of anorexia nervosa after nine months of treatment. A higher score on
'attitudes and feelings' was a protective factor against drop-out from
intervention. CONCLUSIONS: The ANSOCQ is a clinically useful instrument for
measuring motivation to change in adolescents with AN. Two factorial dimensions
explain most of the variation. Self-esteem and coping style are relevant
additional constructs for the understanding of the motivation to change in
anorexia nervosa. TRIAL REGISTRATION: NCT02828956. Retrospectively registered
July 2016.
PMID- 28417004
TI - The effect of relatedness and pack size on territory overlap in African wild
dogs.
AB - BACKGROUND: Spacing patterns mediate competitive interactions between
conspecifics, ultimately increasing fitness. The degree of territorial overlap
between neighbouring African wild dog (Lycaon pictus) packs varies greatly, yet
the role of factors potentially affecting the degree of overlap, such as
relatedness and pack size, remain unclear. We used movement data from 21 wild dog
packs to calculate the extent of territory overlap (20 dyads). RESULTS: On
average, unrelated neighbouring packs had low levels of overlap restricted to the
peripheral regions of their 95% utilisation kernels. Related neighbours had
significantly greater levels of peripheral overlap. Only one unrelated dyad
included overlap between 75%-75% kernels, but no 50%-50% kernels overlapped.
However, eight of 12 related dyads overlapped between their respective 75%
kernels and six between the frequented 50% kernels. Overlap between these more
frequented kernels confers a heightened likelihood of encounter, as the mean
utilisation intensity per unit area within the 50% kernels was 4.93 times greater
than in the 95% kernels, and 2.34 times greater than in the 75% kernels. Related
packs spent significantly more time in their 95% kernel overlap zones than did
unrelated packs. Pack size appeared to have little effect on overlap between
related dyads, yet among unrelated neighbours larger packs tended to overlap more
onto smaller packs' territories. However, the true effect is unclear given that
the model's confidence intervals overlapped zero. CONCLUSIONS: Evidence suggests
that costly intraspecific aggression is greatly reduced between related packs.
Consequently, the tendency for dispersing individuals to establish territories
alongside relatives, where intensively utilised portions of ranges regularly
overlap, may extend kin selection and inclusive fitness benefits from the intra
pack to inter-pack level. This natural spacing system can affect survival
parameters and the carrying capacity of protected areas, having important
management implications for intensively managed populations of this endangered
species.
PMID- 28417003
TI - Migration distance as a selective episode for wing morphology in a migratory
insect.
AB - BACKGROUND: Selective pressures that occur during long-distance migration can
influence morphological traits across a range of taxa. In flying insects,
selection should favour individuals that have wing morphologies that increase
energy efficiency and survival. In monarch butterflies, differences in wing
morphology between migratory and resident populations suggest that migratory
populations have undergone selection for larger (as measured by length and area)
and more elongated (as measured by roundness and aspect ratio) forewings.
However, selection on wing morphology may also occur within migratory
populations, particularly if individuals or populations consistently migrate
different distances. RESULTS: Using 613 monarch butterflies that were collected
on the Mexican wintering grounds between 1976 - 2014, we tested whether monarch
wing traits were associated with migratory distance from their natal areas in
eastern North America (migration range: 774-4430 km), as inferred by stable
hydrogen (delta2H) and -carbon (delta13C) isotopic measurements. Monarchs that
migrated farther distances to reach their overwintering sites tended to have
longer and larger wings, suggesting positive selective pressure during migration
on wing length and area. There was no relationship between migration distances
and either roundness or aspect ratio. CONCLUSIONS: Our results provide
correlative evidence that the migratory period may act as a selective episode on
monarch butterfly wing morphology, although selection during other portions of
the annual cycle, as well as extensive mixing of individuals from various natal
locations on the breeding grounds, likely counteracts directional selection of
migration on morphology.
PMID- 28417005
TI - Reversibility of VasalgelTM male contraceptive in a rabbit model.
AB - BACKGROUND: Development of a non-hormonal long-acting reversible contraceptive
for men could have a significant impact on reducing unintended pregnancies.
VasalgelTM is a high molecular weight polymer consisting of styrene-alt-maleic
acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male
contraceptive device. It forms a hydrogel when implanted into the vasa
deferentia, which prevents the passage of sperm. Previous studies in the rabbit
have proven its efficacy, durability and rapid onset. This study evaluates the
capacity to restore sperm concentrations in ejaculates after a reversal
procedure. METHODS: Sodium bicarbonate was injected into the vasa deferentia
after fourteen months of azoospermia following the injection of two device
variations (Vasalgel 100 and Vasalgel 80). Semen samples were then collected for
six months and sperm characteristics were compared to baseline levels. Samples of
vasa deferentia were obtained for histological examination. RESULTS: Spermatozoa
were present in all subject ejaculates after the reversal procedure. Sperm
concentration and sperm motility were similar to baseline levels after reversal,
while sperm forward progression was significantly lower and normal acrosomes were
not observed. Forward progression percentages increased linearly during six
months of semen collection, however, normal acrosomes were not observed at the
conclusion of the study. Histologically, several vasa deferentia were clear of
the device and contained an intact epithelial lining. A smaller proportion of
tissues contained residual test material. A secondary intraluminal inflammatory
response was seen occasionally in the tissues containing residual material. There
was no difference between the two device variations for studied parameters.
CONCLUSIONS: Vasalgel's prevention of sperm transport for 14 months was reversed
through an intravasal injection of sodium bicarbonate. Post-reversal sperm
concentrations and motility returned to baseline levels during the six-month
follow up. Residual material in the vas lumen or compromised epididymal and vas
deferens function may be resulting in reduced forward progression and loss of
acrosomes during transit through the vas. Reduced forward progression and the
lack of normal acrosomes strongly suggest impaired sperm function.
PMID- 28417006
TI - First report of serotype 23B Streptococcus pneumoniae isolated from an adult
patient with invasive infection in Japan.
AB - Serotype 23B Streptococcus pneumoniae was isolated from a 67-year-old Japanese
patient with meningitis. This isolate was susceptible to penicillin G, while
genotyped as gPISP with a mutation in a penicillin-binding motif in PBP2b. The
23B isolate was assigned to ST11996 that is related to CC439, a dominant group
among serotype 23B.
PMID- 28417007
TI - Reappearance of buffalo-origin-like porcine circovirus type 2 strains in swine
herds in southern China.
AB - Previously, we identified three porcine circovirus type 2 (PCV2) strains in
buffalo meat samples from southern China. In this study, we confirmed the
reappearance of those buffalo-origin-like PCV2 strains in swine herds in this
region, which supported the possible cross-species infection of PCV2 between
buffalos and pigs under field conditions.
PMID- 28417008
TI - Association of gene coding variation and resting metabolic rate in a multi-ethnic
sample of children and adults.
AB - BACKGROUND: Resting metabolic rates (RMR) vary across individuals. Understanding
the determinants of RMR could provide biological insight into obesity and its
metabolic consequences such as type 2 diabetes and cardiovascular diseases.
METHODS: The present study measured RMR using reference standard indirect
calorimetry and evaluated genetic variations from an exome array in a sample of
children and adults (N = 262) predominantly of African and European ancestry with
a wide range of ages (10 - 67 years old) and body mass indices (BMI; 16.9 - 56.3
kg/m2 for adults, 15.1 - 40.6 kg/m2 for children). RESULTS: Single variant
analysis for RMR identified suggestive loci on chromosomes 15 (rs74010762, TRPM1,
p-value = 2.7 * 10-6), 1 (rs2358728 and rs2358729, SH3D21, p-values < 5.8x10-5),
17 (AX-82990792, DHX33, 5.5 * 10-5) and 5 (rs115795863 and rs35433829, C5orf33
and RANBP3L, p-values < 8.2 * 10-5). To evaluate the effect of low frequency
variations with RMR, we performed gene-based association tests. Our most
significant locus was SH3D21 (p-value 2.01 * 10-4), which also contained
suggestive results from single-variant analyses. A further investigation of all
variants within the reported genes for all obesity-related loci from the GWAS
catalog found nominal evidence for association of body mass index (BMI- kg/m2)
associated loci with RMR, with the most significant p-value at rs35433754 (TNKS,
p-value = 0.0017). CONCLUSIONS: These nominal associations were robust to
adjustment for BMI. The most significant variants were also evaluated using
phenome-wide association to evaluate pleiotropy, and genetically predicted gene
expression using the summary statistics implicated loci related to in obesity and
body composition. These results merit further examination in larger cohorts of
children and adults.
PMID- 28417009
TI - Revised definition of predicted left ventricular mass using ambulatory blood
pressure in healthy Korean adults.
AB - BACKGROUND: Left ventricular hypertrophy is influenced by both hemodynamic and
non-hemodynamic factors. Ambulatory blood pressure is correlated with left
ventricular hypertrophy. We established the influences of hemodynamic and non
hemodynamic factors, including ambulatory blood pressure, on variation in left
ventricular mass in healthy Korean adults. METHOD: We included 172 subjects (male
= 71, female = 101), with normal body mass index and blood pressure, in an
analysis of data from the Yangpyung and Yeoju cohort studies and a tertiary
cardiovascular center. Left ventricular mass was calculated using the equation:
[1.04 * (IVSd + LVDd + PWTd) 3-(LDVs3)] * 0.8 + 0.6. Stroke volume was calculated
(mL/beat) using Teichholz's formula. Stroke work (SW in gram-meters/beat [g
m/beat]) was computed as ambulatory systolic BP * stroke volume * 0.0144.
RESULTS: Stroke work was the most important determinant associated with left
ventricular mass (adjusted R2 = 0.442, p < 0.001), independent of height2.7 and
sex. In a regression model including stroke work, height,2.7 and sex, the left
ventricular mass was predicted by the equation: 43.11 + 0.61 * SW (g-m/beat) +
9.21 * height2.7-13.99 * sex (male = 1, female = 2) (constant = 43.11 +/- 25.88,
adjusted R2 = 0.532, p < 0.001). CONCLUSION: We examined ambulatory blood
pressure, as in previous studies, and identified stroke work, height2.7, and sex
as important determinants of left ventricular mass in Korean adults of normal
weight and normal blood pressure. Ambulatory blood pressure is superior to
clinical blood pressure for determining stroke work and predicted left
ventricular mass.
PMID- 28417010
TI - Astrocytes regulate the balance between plasminogen activation and plasmin
clearance via cell-surface actin.
AB - Plasminogen activation is involved in many processes within the central nervous
system, including synaptic plasticity, neuroinflammation and neurodegeneration.
However, the mechanisms that regulate plasminogen activation in the brain still
remain unknown. Here we demonstrate that astrocytes participate in this
regulation by two mechanisms. First, the astrocyte plasma membrane serves as a
surface for plasminogen activation by tissue-type plasminogen activator. This
activation triggers downstream plasmin-dependent processes with important impacts
in brain health and disease, such as fibrinolysis and brain-derived neurotrophic
factor conversion. Second, astrocytes take up plasminogen and plasmin in a
regulated manner through a novel mechanism involving endocytosis mediated by cell
surface actin and triggered by extracellular plasmin activity at the surface of
astrocytes. Following endocytosis, plasminogen and plasmin are targeted to
lysosomes for degradation. Thus, cell-surface actin acts as a sensor of plasmin
activity to induce a negative feedback through plasmin endocytosis. This study
provides evidence that astrocytes control the balance between plasmin formation
and plasmin elimination in the brain parenchyma.
PMID- 28417011
TI - Chemical biology reveals CARF as a positive regulator of canonical Wnt signaling
by promoting TCF/beta-catenin transcriptional activity.
AB - Wnt/beta-catenin signaling regulates multiple biological processes and aberration
of this pathway is frequently observed in human cancers. Previously, we uncovered
NC043 as a small-molecule inhibitor of Wnt/beta-catenin signaling. Here, we
identified CARF as the cellular target of NC043. We found that NC043 binds
directly to CARF through forming a covalent bond with the Cys-516 residue of
CARF. Further study revealed that CARF interacts with Dvl, which potentiates the
Dvl-c-Jun-beta-catenin-TCF transcriptional complex and thus promotes Wnt
signaling activation. NC043 could disrupt the interaction between CARF and Dvl,
thereby impairing Wnt signal transduction. In line with this, knockdown of CARF
in zebrafish leads to impairment of embryonic development, hematopoietic stem
cell generation and caudal fin regeneration. Collectively, we identified CARF as
the cellular target of NC043 and revealed CARF as a positive regulator of
Wnt/beta-catenin signal transduction.
PMID- 28417013
TI - Erratum: Zika virus evades interferon-mediated antiviral response through the co
operation of multiple nonstructural proteins in vitro.
AB - [This corrects the article DOI: 10.1038/celldisc.2017.6.].
PMID- 28417014
TI - Ectogenic tension promotes fibrogenesis of mesenchymal stem cells through
microRNA-21.
PMID- 28417012
TI - Coordinating antigen cytosolic delivery and danger signaling to program potent
cross-priming by micelle-based nanovaccine.
AB - Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by
checkpoint blockade has demonstrated great success in tumor immunotherapy, active
induction of efficient endogenous CTL response by therapeutic vaccines has been
largely hampered by inefficient cytosolic delivery of antigens and coordinated
activation of dendritic cells (DCs) in lymph nodes. Here we show that
polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble
peptides into alpha-helix to enable their efficient cytosolic delivery. The same
PEG-PE micelles also serve as chaperon of TLR4 signaling to coordinate its
adjuvant effect on the same DCs. Furthermore, these nanovaccines effectively
target lymph node DCs. Thus, PEG-PE micelle vaccines program at multiple key
aspects for inducing strong CTL responses and build up a foundation for
combinational tumor therapy.
PMID- 28417015
TI - Characterization and isolation of highly purified porcine satellite cells.
AB - Pig is an important food source and an excellent system to model human diseases.
Careful characterization of the swine skeletal muscle stem cells (satellite
cells) will shed lights on generation of swine skeletal muscle disease model and
efficient production of porcine meat for the food industry. Paired box protein 7
(Pax7) is a highly conserved transcription factor shared by satellite cells from
various species. However, the sequence of Pax7 has not been characterized in pig.
The lack of method to isolate highly purified satellite cells hinders the
thorough characterization of the swine satellite cells. Here we found molecular
markers for swine satellite cells and revealed that the porcine satellite cells
were heterogeneous in various pieces of skeletal muscle. We further developed a
method to isolate highly purified satellite cells directly from porcine muscles
using fluorescence-activated cell sorting. We next characterized the
proliferation and differentiation abilities of isolated satellite cells in vitro;
and found that long-term culturing of satellite cells in vitro led to stemness
loss.
PMID- 28417016
TI - HMGB1 release by H2O2-induced hepatocytes is regulated through calcium overload
and 58-F interference.
AB - HMGB1 is passively released by injured or dying cells and aggravates inflammatory
processes. The release of HMGB1 and calcium overload have each been reported to
be important mediators of H2O2-induced injury. However, a potential connection
between these two processes remains to be elucidated. In the present study, we
employed H2O2-induced hepatocytes to investigate how calcium overload takes place
during cellular injury and how the extracellular release of HMGB1 is regulated by
this overload. In addition, we investigated the use of 58-F, a flavanone
extracted from Ophiopogon japonicus, as a potential therapeutic drug. We show
that the PLCgamma1-IP3R-SOC signalling pathway participates in the H2O2-induced
disturbance of calcium homoeostasis and leads to calcium overload in hepatocytes.
After a rise in intracellular calcium, two calcium-dependent enzymes, PKCalpha
and CaMKIV, are activated and translocated from the cytoplasm to the nucleus to
modify HMGB1 phosphorylation. In turn, this promotes HMGB1 translocation from the
nucleus to the cytoplasm and subsequent extracellular release. 58-F effectively
rescued the hepatocytes by suppressing the PLCgamma1-IP3R-SOC signalling pathway
and decreasing the calcium concentration in cells, thus reducing HMGB1 release.
PMID- 28417017
TI - Galectin-1 inhibition attenuates profibrotic signaling in hypoxia-induced
pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising
from epithelial injury, aberrant fibroblast growth, and excessive deposition of
extracellular matrix. Repeated epithelial injury elicits abnormal wound repair
and lung remodeling, often associated with alveolar collapse and edema, leading
to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult
that contributes to pulmonary fibrosis (PF) and define its molecular roles in
profibrotic activation of lung epithelial cells. Hypoxia increased transcription
of profibrotic genes and altered the proteomic signatures of lung epithelial
cells. Network analysis of the hypoxic epithelial proteome revealed a crosstalk
between transforming growth factor-beta1 and FAK1 (focal adhesion kinase-1)
signaling, which regulated transcription of galectin-1, a profibrotic molecule.
Galectin-1 physically interacted with and activated FAK1 in lung epithelial
cells. We developed a novel model of exacerbated PF wherein hypoxia, as a
secondary insult, caused PF in mice injured with subclinical levels of bleomycin.
Hypoxia elevated expression of phosphorylated FAK1, galectin-1, and alpha-smooth
muscle actin and reduced caspase-3 activation, suggesting aberrant injury repair.
Galectin-1 inhibition caused apoptosis in the lung parenchyma and reduced FAK1
activation, preventing the development of hypoxia-induced PF. Galectin-1
inhibition also attenuated fibrosis-associated lung function decline. Further,
galectin-1 transcript levels were increased in the lungs of IPF patients. In
summary, we have identified a profibrotic role of galectin-1 in hypoxia signaling
driving PF.
PMID- 28417019
TI - Heme oxygenase 1 governs the cytoskeleton at filopodia: pulling the brakes on the
migratory capacity of prostate tumoral cells.
PMID- 28417018
TI - DNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system
and inflammation.
AB - PP2C serine-threonine phosphatase, Wip1, is an important regulator of stress
response. Wip1 controls a number of critical cellular functions: proliferation,
cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy.
Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic
progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone
marrow and peripheral blood. The Wip1-/- mice display immunodeficiency, abnormal
lymphoid histopathology in thymus and spleen, defects in B- and T-cell
differentiation, as well as susceptibility to viral infection. At the same time,
Wip1 knockout mice exhibit pro-inflammatory phenotype in skin and intestine in
the model of inflammatory bowel disease (IBD) with elevated levels of
inflammation-promoting cytokines TNF-alpha, IL-6, IL-12, IL-17. Several Wip1
downstream targets can mediate Wip1 effects on hematopoietic system including,
p53, ATM, p38MAPK kinase, NFkB, mTOR. Here, we summarized the current knowledge
on the role of Wip1 in the differentiation of various hematopoietic lineages and
how Wip1 deficiency affects the functions of immune cells.
PMID- 28417020
TI - Anatomical Research: Misconceptions and opportunities.
PMID- 28417021
TI - Sentinel Lymph Node Biopsy: A new approach in the management of head and neck
cancers.
AB - Cervical lymph node metastasis affects the prognosis and overall survival rate of
and therapeutic planning for patients with head and neck squamous cell carcinomas
(HNSCCs). However, advanced diagnostic modalities still lack accuracy in
detecting occult neck metastasis. A sentinel lymph node biopsy is a minimally
invasive auxiliary method for assessing the presence of occult metastatic disease
in a patient with a clinically negative neck. This technique increases the
specificity of neck dissection and thus reduces morbidity among oral cancer
patients. The removal of sentinel nodes and dissection of the levels between the
primary tumour and the sentinel node or the irradiation of target nodal basins is
favoured as a selective treatment approach; this technique has the potential to
become the new standard of care for patients with HNSCCs. This article presents
an update on clinical applications and novel developments in this field.
PMID- 28417022
TI - Role of Travel Motivations, Perceived Risks and Travel Constraints on Destination
Image and Visit Intention in Medical Tourism: Theoretical model.
AB - Travel motivations, perceived risks and travel constraints, along with the
attributes and characteristics of medical tourism destinations, are important
issues in medical tourism. Although the importance of these factors is already
known, a comprehensive theoretical model of the decision-making process of
medical tourists has yet to be established, analysing the intricate relationships
between the different variables involved. This article examines a large body of
literature on both medical and conventional tourism in order to propose a
comprehensive theoretical framework of medical tourism decision-making. Many
facets of this complex phenomenon require further empirical investigation.
PMID- 28417023
TI - The Science of Anatomy: A historical timeline.
PMID- 28417024
TI - New Classification for Heart Failure with Mildly Reduced Ejection Fraction:
Greater clarity or more confusion?
AB - The latest European Society of Cardiology (ESC) guidelines for the diagnosis and
management of heart failure include a new patient group for those with heart
failure with mildly reduced ejection fraction (HFmrEF). By defining this group of
patients as a separate entity, the ESC hope to encourage more research focusing
on patients with HFmrEF. Previously, patients with this condition were caught
between two classifications-heart failure with reduced ejection fraction and
heart failure with preserved ejection fraction. Hopefully, the inclusion of new
terminology will not increase confusion, but rather aid our understanding of
heart failure, a complex clinical syndrome.
PMID- 28417025
TI - Dorsal Phalloplasty to Preserve Penis Length after Penile Prosthesis
Implantation.
AB - OBJECTIVES: Following penile prosthesis implantation (PPI), patients may complain
of a decrease in visible penis length. A dorsal phalloplasty defines the
penopubic junction by tacking pubic skin to the pubis, revealing the base of the
penis. This study aimed to evaluate the efficacy of a dorsal phalloplasty in
increasing the visible penis length following PPI. METHODS: An inflatable penile
prosthesis was implanted in 13 patients with severe erectile dysfunction (ED) at
the Kamal Shaeer Hospital, Cairo, Egypt, from January 2013 to May 2014. During
the surgery, nonabsorbable tacking sutures were used to pin the pubic skin to the
pubis through the same penoscrotal incision. Intraoperative penis length was
measured before and after the dorsal phalloplasty. Overall patient satisfaction
was measured on a 5-point rating scale and patients were requested to
subjectively compare their postoperative penis length with memories of their
penis length before the onset of ED. RESULTS: Intraoperatively, the dorsal
phalloplasty increased the visible length of the erect penis by an average of
25.6%. The average length before and after tacking was 10.2 +/- 2.9 cm and 13.7
+/- 2.8 cm, respectively (P <0.002). Postoperatively, seven patients (53.8%)
reported a longer penis, five patients (38.5%) reported no change in length and
one patient (7.7%) reported a slightly shorter penis. The mean overall patient
satisfaction score was 4.9 +/- 0.3. None of the patients developed postoperative
complications. CONCLUSION: A dorsal phalloplasty during PPI is an effective
method of increasing visible penis length, therefore minimising the impression of
a shorter penis after implantation.
PMID- 28417026
TI - Cardiovascular Complications of Acute Amphetamine Abuse: Cross-sectional study.
AB - OBJECTIVES: This study aimed to evaluate cardiovascular complications among
patients who abuse amphetamines. METHODS: This cross-sectional study took place
between April 2014 and April 2015 among 3,870 patients referred to the Toxicology
Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences,
Tehran, Iran. Those with clinical signs of drug abuse and positive urine
screening tests were included in the study, while cases of chronic abuse were
excluded. Cardiac complications were evaluated via electrocardiography (ECG) and
transthoracic echocardiography. RESULTS: A total of 230 patients (5.9%) had a
history of acute amphetamine abuse and positive urine tests. Of these, 32
patients (13.9%) were <20 years old and 196 (85.2%) were male. In total, 119
(51.7%) used amphetamine and methamphetamine compounds while 111 (48.3%) used
amphetamines with morphine or benzodiazepines. The most common ECG finding was
sinus tachycardia (43.0%), followed by sinus tachycardia plus a prolonged QT
interval (34.3%). Mean creatine kinase-MB and troponin I levels were 35.9 +/- 4.3
U/mL and 0.6 +/- 0.2 ng/mL, respectively. A total of 60 patients (26.1%) were
admitted to the Intensive Care Unit. The majority (83.3%) of these patients had
normal echocardiography results. The mean aortic root diameter (ARD) was 27.2 +/-
2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%), three
of whom subsequently died. CONCLUSION: According to these findings, cardiac
complications were common among Iranian patients who abuse amphetamines, although
the majority of patients had normal echocardiography and ECG findings.
PMID- 28417027
TI - Decision-to-Delivery Time Intervals in Emergency Caesarean Section Cases:
Repeated cross-sectional study from Oman.
AB - OBJECTIVES: In cases of fetal intolerance to labour, meeting the standard
decision-to-delivery time interval (DDI) of <=30 minutes is challenging. This
study aimed to assess DDIs in emergency Caesarean section (CS) cases to identify
factors causing DDI delays and the impact of a delayed DDI on perinatal outcomes.
METHODS: This repeated cross-sectional study included all emergency CS procedures
performed due to acute fetal distress, antepartum haemorrhage or umbilical cord
prolapse at the Nizwa Hospital, Nizwa, Oman. Three audit cycles of three months
each were conducted between April 2011 and June 2013, including an initial
retrospective cycle and two prospective cycles following the implementation of
improvement strategies to address factors causing DDI delays. Poor perinatal
outcomes were defined as Apgar scores of <7 at five minutes, admission to the
Special Care Baby Unit (SCBU) or a stillbirth. RESULTS: In the initial cycle, a
DDI of <=30 minutes was achieved in 23.8% of 84 cases in comparison to 44.6% of
83 cases in the second cycle. In the third cycle, 60.8% of 79 women had a DDI of
<=30 minutes (P <0.001). No significant differences in perinatal outcomes for
cases with a DDI of <=30 minutes versus 31-60 minutes were observed; however, a
DDI of >60 minutes was significantly associated with poor neonatal outcomes in
terms of increased SCBU admissions and low Apgar scores (P <0.001 each). Factors
causing DDI delays included obtaining consent for the CS procedure, a lack of
operating theatre availability and moving patients to the operating theatre.
CONCLUSION: The identification of factors causing DDI delays may provide
opportunities to improve perinatal outcomes.
PMID- 28417028
TI - General Anaesthesia Protocols for Patients Undergoing Electroconvulsive Therapy:
Retrospective analysis of 504 sessions over a five-year period at a tertiary care
hospital in Oman.
AB - OBJECTIVES: This study aimed to review general anaesthesia protocols for patients
undergoing electroconvulsive therapy (ECT) at a tertiary care hospital in Oman,
particularly with regards to clinical profile, potential drug interactions and
patient outcomes. METHODS: This retrospective study took place at the Sultan
Qaboos University Hospital (SQUH), Muscat, Oman. The electronic medical records
of patients undergoing ECT at SQUH between January 2010 and December 2014 were
reviewed for demographic characteristics and therapy details. RESULTS: A total of
504 modified ECT sessions were performed on 57 patients during the study period.
All of the patients underwent a uniform general anaesthetic regimen consisting of
propofol and succinylcholine; however, they received different doses between
sessions, as determined by the treating anaesthesiologist. Variations in drug
doses between sessions in the same patient could not be attributed to any
particular factor. Self-limiting tachycardia and hypertension were periprocedural
complications noted among all patients. One patient developed aspiration
pneumonitis (1.8%). CONCLUSION: All patients undergoing ECT received a general
anaesthetic regimen including propofol and succinylcholine. However, the
interplay of anaesthetic drugs with ECT efficacy could not be established due to
a lack of comprehensive data, particularly with respect to seizure duration. In
addition, the impact of concurrent antipsychotic therapy on anaesthetic dose and
subsequent complications could not be determined.
PMID- 28417029
TI - Contraceptive Utilisation Among Mothers of Reproductive Age in Ajman, United Arab
Emirates.
AB - OBJECTIVES: This study aimed to determine contraceptive utilisation among mothers
aged 18-49 years old in Ajman, United Arab Emirates (UAE). METHODS: This cross
sectional study was carried out from May to November 2013. A total of 400
participants were recruited from two primary healthcare centres and one private
hospital in Ajman. An interviewer-administered validated questionnaire was used
for data collection. RESULTS: The frequency of previous and current contraceptive
use was 68.0% and 61.8%, respectively. Expatriates more frequently used
contraceptives in comparison to Emiratis (77.3% versus 54.3%, respectively).
Contraceptive use increased significantly with age (75.5% among >35-year-olds
versus 57.3% among <=25-year-olds; P <0.050) and education level (83.3% among
postgraduates versus 60.0% among those with primary education; P <0.050). In
addition, contraceptive use was significantly higher among those living in a
nuclear family system (P <0.050). A univariate analysis indicated significant
associations between contraceptive use and age, nationality, education level,
type of family system, employment sector, parity, knowledge of birth control
measures and source of birth control information (P <0.050 each). However, no
significant associations were found via multivariate analysis. CONCLUSION:
Healthcare practitioners can play a pivotal role in providing contraceptive
advice which could lead to an improvement in contraceptive utilisation. Efforts
are recommended to raise awareness regarding newer forms of contraceptives among
mothers of reproductive age in the UAE.
PMID- 28417030
TI - Knowledge and Attitudes Towards Basic Life Support Among Health Students at a
Saudi Women's University.
AB - OBJECTIVES: Awareness of basic life support (BLS) is paramount to ensure the
provision of essential life-saving medical care in emergency situations. This
study aimed to measure knowledge of BLS and attitudes towards BLS training among
female health students at a women's university in Saudi Arabia. METHODS: This
prospective cross-sectional study took place between January and April 2016 at
five health colleges of the Princess Nourah bint Abdulrahman University, Riyadh,
Saudi Arabia. All 2,955 students attending the health colleges were invited to
participate in the study. Participants were subsequently asked to complete a
validated English-language questionnaire which included 21 items assessing
knowledge of BLS and six items gauging attitudes to BLS. RESULTS: A total of
1,349 students completed the questionnaire (response rate: 45.7%). The mean
overall knowledge score was very low (32.7 +/- 13.9) and 87.9% of the
participants had very poor knowledge scores. A total of 32.5% of the participants
had never received any BLS training. Students who had previously received BLS
training had significantly higher knowledge scores (P <0.001), although their
knowledge scores remained poor. Overall, 77.0% indicated a desire to receive
additional BLS training and 78.5% supported mandatory BLS training. CONCLUSION:
Overall knowledge about BLS among the students was very poor; however, attitudes
towards BLS training were positive. These findings call for an improvement in BLS
education among Saudi female health students so as to ensure appropriate
responses in cardiac arrest or other emergency situations.
PMID- 28417031
TI - Knowledge, Practice and Self-Efficacy in Evidence-Based Practice among Midwives
in East Iran.
AB - OBJECTIVES: The successful implementation of evidence-based practice (EBP) can
lead to appropriate and effective midwifery care during pregnancy, childbirth and
in the postnatal period. However, levels of knowledge and confidence in one's
ability to apply EBP are related to its effective implementation. This study
aimed to investigate levels of knowledge, practice of and self-efficacy towards
the use of EBP among midwives in East Iran. METHODS: This cross-sectional study
took place between January and February 2016 and involved 98 midwives employed at
two hospitals and all four urban health care centres in Torbat-e Heydariyeh,
Iran. Two subscales of the Evidence-Based Practice Questionnaire were used to
assess participants' knowledge and practice of EBP, respectively, while a
modified version of a previously described scale was used to determine self
efficacy. RESULTS: A total of 76 midwives participated in the study (response
rate: 77.6%). Mean knowledge, practice and self-efficacy scores were 4.48 +/-
0.94, 3.53 +/- 0.68 and 2.80 +/- 0.81, respectively. Significant relationships
were found between mean self-efficacy, practice and knowledge scores and
proficiency in English language (P = 0.001 each) and statistical methods (P
<0.050 each). Additionally, significant relationships were found between
knowledge and practice of EBP and proficiency in the use of databases (P <0.050
each). Knowledge and self-efficacy scores were significantly correlated with
practice (P = 0.001 each). CONCLUSION: These findings demonstrate a need for
improvement in the self-efficacy, practice and knowledge of EBP among midwives in
East Iran. Interventions that promote these factors may help increase the use of
EBP in this population.
PMID- 28417032
TI - Vision Screening of Ophthalmic Nursing Staff in a Tertiary Eye Care Hospital:
Outcomes and ocular healthcare-seeking behaviours.
AB - OBJECTIVES: This study aimed to evaluate ocular healthcare-seeking behaviours and
vision screening outcomes of nursing staff at a tertiary eye care hospital.
METHODS: This study was conducted between April and September 2016 among all 500
nurses employed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Data were collected on age, gender, use of visual aids, the presence of diabetes,
a history of refractive surgery and date of last ocular health check-up.
Participants were tested using a handheld SpotTM Vision Screener (Welch Allyn
Inc., Skaneateles Falls, New York, USA). RESULTS: A total of 150 nurses
participated in the study (response rate: 30.0%). The mean age was 41.2 +/- 8.9
years old. Distance spectacles, reading spectacles and both types of spectacles
were used by 37 (24.7%), 32 (21.3%) and 10 (6.7%) nurses, respectively. A total
of 58 nurses (38.7%) failed the vision screening test. Visual defects were
detected for the first time in 13 nurses (8.7%). With regards to regular eye
checkups, 77 participants (51.3%) reported acceptable ocular healthcare-seeking
behaviours; this factor was significantly associated with age and the use of
visual aids (P <0.01 each). CONCLUSION: A high proportion of participants failed
the vision screening tests and only half displayed good ocular healthcare-seeking
behaviours. This is concerning as ophthalmic nurses are likely to face fewer
barriers to eye care services than the general population.
PMID- 28417033
TI - Validation of a Persian Short-Form Version of a Standardised Questionnaire
Assessing Oral Cancer Knowledge, Practice and Attitudes Among Dentists.
AB - OBJECTIVES: Oral cancer is a global health problem; however, many dentists lack
the necessary skills, knowledge and capacity to diagnose oral cancers early. This
study aimed to examine the validity and reliability of a Persian short-form
version of a standardised questionnaire to assess dentists' knowledge, practice
and attitudes towards oral cancer. METHODS: This cross-sectional analytical study
was carried out in May 2015 in Tehran, Iran. An original 39-item English-language
questionnaire developed by Yellowitz et al. was translated into Persian using
forward and backward translation methods. A total of 15 dental professionals were
asked to assess the questionnaire for content validity. Based on their feedback,
a 20-item short-form version was prepared, including six demographic, six
knowledge, four attitude and four practice items. The translated short-form
questionnaire was subsequently distributed to 973 general dental practitioners
attending a dental conference in Tehran. Internal consistency and reliability
were assessed with Cronbach's alpha coefficient and item-total correlation
calculations. RESULTS: A total of 13 professionals and 313 general dentists
participated in the study (response rates: 86.7% and 32.2%, respectively). After
the elimination of six items (two knowledge, two attitude and two practice
items), the validity and reliability of the questionnaire was confirmed.
CONCLUSION: The final Persian 14-item version of the questionnaire had acceptable
validity and internal consistency. These results indicate that researchers can
use this translated short-form version to evaluate oral cancer knowledge,
attitudes and practices among Persian-speaking dentists; this will allow for a
comparison of data between different populations.
PMID- 28417034
TI - Knowledge Regarding Secondary Prevention Lifestyle Practices Among Patients with
Ischaemic Heart Disease in Oman: Pilot study.
AB - OBJECTIVES: Secondary prevention of ischaemic heart disease (IHD) is very
important. This study aimed to assess knowledge of necessary lifestyle changes
among Omani patients diagnosed with IHD. METHODS: This cross-sectional pilot
study took place between October 2015 and February 2016 at the Sultan Qaboos
University Hospital (SQUH), Muscat, Oman. A total of 30 random patients with IHD
from the Cardiology Outpatient Clinic of SQUH were included. A 30-item survey was
used to determine patients' knowledge of necessary lifestyle practices following
their IHD diagnosis, with scores of <70% indicating poor knowledge. RESULTS:
Overall, 21 patients (70.0%) had low knowledge levels. Scores ranged from 38.9
94.4% (mean: 60.7% +/- 14.1%). No demographic factors were found to predict low
scores, although there were some differences in individual questions. CONCLUSION:
Low knowledge levels regarding lifestyle changes were observed among IHD patients
in Oman. More efforts should be made to educate these patients for the secondary
prevention of IHD.
PMID- 28417035
TI - Jaw Osteomyelitis as a Complication of Sickle Cell Anaemia in Three Omani
Patients: Case reports and literature review.
AB - Sickle cell anaemia (SCA) is a common haemoglobinopathy among people from the
Middle East, the Afro-Caribbean region, the Mediterranean and East India. While
osteomyelitis of the long bones is a well-documented complication of SCA, there
are few documented cases of SCA patients presenting with jaw osteomyelitis. We
report three SCA patients with chronic jaw osteomyelitis who presented to the
Department of Oral Health, Sultan Qaboos University Hospital, Muscat, Oman,
between 2009 and 2013. Two of the patients had osteomyelitis of the mandible and
the third had osteomyelitis of the maxilla. In addition, a brief review of the
literature is presented focusing on the clinical presentation, diagnosis and
management of jaw osteomyelitis among patients with SCA.
PMID- 28417036
TI - Verrucous Hyperplasia: Case report and differential diagnosis.
AB - Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can
transform into verrucous carcinoma (VC), its malignant but clinically similar
counterpart. These entities can be distinguished by the lack of invasive growth
in VH cases; as such, it is essential to include a margin with adequate depth
when performing a biopsy of the epithelium of the lesion. We report an 80-year
old male patient who presented to the Bapuji Dental College & Hospital,
Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the
inside of his cheek. The patient was treated with wide surgical excision of the
lesion and a diagnosis of VH was made based on histopathological features. There
was no evidence of recurrence at a five-year follow-up. This report highlights
the histological variations, pathogenesis and differential diagnosis of VH.
PMID- 28417037
TI - Additional Muscle Slip of Bicipital Aponeurosis and its Anomalous Relationship
with the Median Cubital Vein.
AB - The cubital region of the arm is a common site for recording blood pressure,
taking blood for analysis and administering intravenous therapy and blood
transfusions. During the routine dissection of a 70-year-old male cadaver at the
Kasturba Medical College, Manipal, Karnataka, India, in 2015, it was observed
that the aponeurotic insertion of the biceps brachii muscle divided into two
slips. The medial slip fused normally with the deep fascia of the forearm, while
flexor carpi radialis muscle fibres originated from the lateral slip. There was
also a single vein in the forearm, the cephalic vein, which bifurcated to form
the median cubital vein and the cephalic vein proper. The median cubital vein,
further reinforced by the radial vein, passed deep to the two slips of the
bicipital aponeurosis and then continued as the basilic vein. During
venepuncture, medical practitioners should be aware of potential cubital fossa
variations which could lead to nerve entrapment syndromes.
PMID- 28417038
TI - Anomalous Innervation of the Median Nerve in the Arm in the Absence of the
Musculocutaneous Nerve.
AB - The brachial plexus innervates the upper extremities. While variations in the
formation of the brachial plexus and its terminal branches are quite common, it
is uncommon for the median nerve to innervate the muscles of the arm. During the
dissection of an elderly male cadaver at the Department of Anatomy, All India
Institute of Medical Sciences, New Delhi, India, in 2016, the coracobrachialis
muscle was found to be supplied by a direct branch from the lateral root of the
median nerve and the musculocutaneous nerve was absent. The branches of the
median nerve supplied the biceps brachii and brachialis muscles and the last
branch continued as the lateral cutaneous nerve of the forearm. These variations
may present atypically in cases of arm flexor paralysis or sensory loss on the
lateral forearm. Knowledge of these variations is important in surgeries and
during the administration of regional anaesthesia near the shoulder joint and
upper arm.
PMID- 28417039
TI - A True Human Tail in a Neonate: Case report and literature review.
AB - A true human tail is a benign vestigial caudal cutaneous structure composed of
adipose, connective tissue, muscle, vessels, nerves and mechanoreceptors. A true
human tail can be distinguished from a pseudotail as the latter is commonly
associated with underlying spinal dysraphism, which requires specialised
management. True human tails are very rare, with fewer than 40 cases reported to
date. We report a healthy one-day-old male newborn who was referred to the
Bharath Hospital, Kottayam, Kerala, India, in 2014 with a cutaneous appendage
arising from the lumbosacral region. Magnetic resonance imaging of the spine
ruled out spinal dysraphism. The appendage was removed by simple surgical
excision. Clinicians should emphasise use of 'true tail' and 'pseudotail' as
specific disparate terms as the clinical, radiological and histological findings
of these conditions differ significantly, along with management strategies and
outcomes.
PMID- 28417040
TI - Unusual Branching Pattern of the Lateral Cord of the Brachial Plexus Associated
with Neurovascular Compression: Case report.
AB - The brachial plexus consists of a network of nerves that innervates the upper
limbs and its musculature. We report a rare formation of the lateral cord of the
brachial plexus observed during the dissection of a 47-year-old male cadaver at
the Department of Anatomy, Vardhman Mahavir Medical College, New Delhi, India, in
2016. The lateral cord was exceptionally long with twin lateral pectoral nerves
and twin lateral roots of the median nerve. The proximal lateral root of the
median nerve was thin in comparison to the medial root of the median nerve. The
distal lateral root of the median nerve was thicker and followed an unusual
course through the coracobrachialis muscle. In the lower third of the arm, the
median nerve and the brachial artery-along with its vena comitans-spanned through
the brachialis muscle. Surgeons, anaesthesiologists, radiologists and anatomists
should be aware of such anatomical variations as they may result in neurovascular
compression.
PMID- 28417042
TI - Accessory Duct of the Submandibular Gland.
PMID- 28417041
TI - Focal Scalp Hair Heterochromia in an Infant.
AB - Hair heterochromia involves the presence of two different non-artificially
induced colours of hair in the same individual which can be due to either iron
deficiency anaemia, genetic mutations or mosaicism. We report a six-month old
male infant who presented to the Department of Dermatology, Saham Hospital,
Saham, Oman, in 2013 with focal scalp hair heterochromia without any detectable
underlying abnormalities. The area of heterochromia was still noticeable at a one
year follow-up.
PMID- 28417043
TI - Extensive Fixed Drug Eruption Due to Diclofenac.
PMID- 28417044
TI - MEDLINE(r) Indexing of the Sultan Qaboos University Medical Journal: A great leap
forward for biomedical research and publishing in the Gulf region.
PMID- 28417045
TI - A Turning Point for Paediatric Developmental Services in Oman: Establishment of a
national autism screening programme.
PMID- 28417046
TI - Re: Coexistence of Autism Spectrum Disorders Among Three Children with Tuberous
Sclerosis Complex: Case reports and review of literature.
PMID- 28417047
TI - Clinical significance of SNP (rs2596542) in histocompatibility complex class I
related gene A promoter region among hepatitis C virus related hepatocellular
carcinoma cases.
AB - The major histocompatibility complex class I-related gene A (MICA) is an antigen
induced by stress and performs an integral role in immune responses as an anti
infectious and antitumor agent. This work was designed to investigate whether
(SNP) rs2596542C/T in MICA promoter region is predictive of liver cirrhosis (LC)
and hepatocellular carcinoma (HCC) or not. Forty-seven healthy controls and 94
HCV-infected patients, subdivided into 47 LC and 47 HCC subjects were enrolled in
this study. SNP association was studied using real time PCR and soluble serum
MICA concentration was measured using ELISA. Results showed that heterozygous
genotype rs2596542CT was significantly (P = 0.022) distributed between HCC and LC
related CHC patients. The sMICA was significantly higher (P = 0.0001) among HCC
and LC. No significant association (P = 0.56) between rs2596542CT genotypes and
sMICA levels was observed. Studying SNP rs2596542C/T association with HCC and LC
susceptibility revealed that statistical significant differences (P = 0.013, P =
0.027) were only observed between SNP rs2596542C/T and each of HCC and LC,
respectively, versus healthy controls, indicating that the rs2596542C/T genetic
variation is not a significant contributor to HCC development in LC patients.
Moreover, the T allele was considered a risk factor for HCC and LC vulnerability
in HCV patients (OR = 1.93 and 2.1, respectively), while the C allele contributes
to decreasing HCC risk. Therefore, SNP (rs2596542C/T) in MICA promoter region and
sMICA levels might be potential useful markers in the assessment of liver disease
progression to LC and HCC.
PMID- 28417048
TI - Is tricuspid valve really tricuspid?
AB - Advancement in imaging techniques and interventional cardiology procedures have
generated renewed interest in anatomy of tricuspid valve complex. The purpose of
the present study was to characterize the morphology of tricuspid valve leaflets
using objective criteria. Thirty-six embalmed cadaveric hearts were utilized for
the present study. Leaflet morphology was studied using newly defined criteria.
Commissural zones were identified and leaflets were delineated. Presence of
scallops was also recorded. Single leaflet was observed in six cases, double in
26 cases, and triple in four cases. The anterior leaflet is large with multiple
scallops and frequently accrues portion of inferior leaflet. The septal leaflet
is in the form of a plateau and also frequently accrues parts of inferior
leaflet. The inferior leaflet rarely occurs as independent leaflet. A wide un
indented basal zone exists across the valve leaflets. The study found that the
tricuspid valve is rarely tricuspid. It also generated the hypotheses that the
tricuspid valve does not open completely due to presence of a wide basal zone and
the valve does not close completely owing to incongruence and lack of coaptation
of leaflets. The findings provide clear understanding of leaflet morphology of
tricuspid valve. This will help imaging specialists for interpretation of images
and cardiologists for interventional procedures. The findings also enhance our
understanding of pathophysiology of conditions like functional tricuspid
regurgitation.
PMID- 28417049
TI - Morphometric study of tensor of vastus intermedius in South Indian population.
AB - Tensor of vastus intermedius is a newly discovered muscle located between vastus
lateralis and vastus intermedius. The purpose of this study was to investigate
the detailed morphology of tensor of vastus intermedius, specifically to provide
data pertaining to the attachments, innervations, variation in the types and its
morphometry in South Indian population. The tensor of vastus intermedius was
studied in thirty six cadaveric lower limbs using macrodissection techniques. The
origin of the muscle was from upper part of intertrochanteric line and anterior
part of greater trochanter of femur inserted to medial aspect of upper border of
patella. The muscle was classified into four types based on the origin and also
the aponeurosis course with independent type (type 1) being common. The mean and
standard deviation of the length of tensor of vastus intermedius and aponeurosis
were 145.40+/-37.55 mm and 193.55+/-42.32 mm, respectively. The results of the
study suggest that tensor of vastus intermedius is variable and the information
provided regarding the attachments, types and quantitative data will contribute
to the existing knowledge of the muscle.
PMID- 28417050
TI - Venezuelan surgeons view concerning teaching human anatomical dissection.
AB - Currently, the importance of human anatomical dissection have come under debate
in many countries but there are not references in Venezuela on this concern. This
survey's aim is to assess the insights of Venezuelan surgeons and their outlines
of usage of human anatomical dissection in teaching and learning human anatomy.
Sixty-five Venezuelan surgeons at the Centro Medico Docente La Trinidad completed
an anonymous survey on current and future teaching practices in human anatomy.
Eighty-nine point two three percent of surveyed (n=58) conferred importance to
human anatomical dissection despite the arrival of new innovations in learning
human anatomy. The group surveyed view human anatomical dissection-based teaching
as the most beneficial method of teaching human anatomy and it should be
bolstered in human anatomical education with matching use of three-dimensional
computerized tomography imaging as a complementary form for teaching and
learning.
PMID- 28417051
TI - Morphology of cat vomeronasal organ non-sensory epithelium during postnatal
development.
AB - The vomeronasal organ has an important role in mammal's social and sexual
behaviours. In addition, it mediates defensive behavior through detection of
protein pheromone homologues. In this work, a detailed morphological description
of the postnatal development of the non-sensory epithelium (NSE) lining the
vomeronasal duct (VND) of the female cat is provided using various histological
techniques. The study focused on newborn, 2 weeks, 4 weeks, and 8 weeks of
postnatal ages using four animals for each age. We report here for the first time
that three types of NSE line the rostral segment of the VND; nonkeratinized
stratified squamous epithelium, stratified cuboidal epithelium, and ciliated
pseudo stratified columnar ciliated epithelium with goblet cells and that the VND
undergoes 90 degrees a change in its its axis from the vertical position
caudally to the horizontal position rostral. The NSE which lines the lateral side
of the VND middle segment is consists of cliated pseudostratified columnar
epithelium without goblet cells. In addition to basal cells, the NSE contains
ciliated and three types of nonciliated columnar epithelial cells (dark, light,
and unstained). Mitotic figures were observed only in the basal cells layer
during the first 2 weeks of postnatal development. Intraepithelial invading
inflammatory cells were uncommon. Scanning electron microscopy revealed unevenly
distributed long cilia intermingled with microvillar processes and intervening
short microvillar processes. These projecting cilia and microvilli revealed a
gradual increase in their height during development toward maturity.
PMID- 28417052
TI - Relationship between meiotic spindles visualization and intracytoplasmic sperm
injection outcomes in human oocytes.
AB - In assisted reproductive techniques, the operator attempts to select
morphologically best embryos to predict embryo viability. Development of
polarized light microscope, which evaluates the oocytes' spindles according to
birefringence of living cells, had been helpful in oocyte selection. The aim of
this study is evaluating the relationship between meiotic spindles visualization
and intracytoplasmic sperm injection (ICSI) outcomes in human oocytes. In this
study, 264 oocytes from 24 patients with an average age of 30.5+/-7.5 years with
infertility duration of 1 to 10 years were collected. The oocytes were randomly
allocated to the control injection group (n=126) and the oocyte imaging group
(spindle-aligned group) (n=138). In the spindle-aligned group, the meiotic
spindle was identified by means of polarized light microscope to align the
spindle at 6 or 12 o'clock. Then the spindle-aligned group was divided into three
sub-groups based on spindle morphology: fine, average, and (poor). After ICSI,
embryos were checked every 24 hours and scored; 72 hours later, high-grade
embryos were transferred intravaginally to uterus. This study showed that the
fertilization rate in the spindle-aligned group was higher than the control group
(P<0.05). After cleavage, a positive correlation was observed between spindle
morphology and embryo morphology. Among the sub-groups of spindle-aligned group,
the embryos' morphology of the fine group was better than the other subgroups and
embryos of the poor group had lower quality and more fragmentation. The results
revealed that the selection of oocytes based on meiotic spindle imaging can
significantly improve the rate of fertilization and embryo cleavage and certainly
increase the rate of implantation.
PMID- 28417053
TI - Pacinian corpuscle-like structure in the digital tendon sheath and nail bed: a
study using late-stage human fetuses.
AB - Pacinian corpuscle-like structures were identified in the digital tendon sheaths
and nail beds of hands obtained from eight of 12 human fetuses of gestational age
20-34 weeks (crown-rump length, 150-290 mm). The aberrant corpuscles were present
in tight fibrous tissue connecting the flexor tendon sheath to the dorsal
aponeurosis (138 corpuscles in the thumbs and all fingers of eight fetuses);
loose fibrous tissue inside the sheath on the dorsal side of the tendon (37
corpuscles in the thumbs and all fingers of four fetuses); and the nail bed (10
clusters in the thumbs and second fingers of four smaller fetuses). The aberrant
corpuscles in the tendon sheath were classified into two types: thin and short,
with tightly packed lamellae, of diameter 20-40 um and length 20-200 um; and
thick and long, with loosely packed lamellae, of diameter 70-150 um and length
0.5-1.5 mm. The small corpuscles tended to form clusters, each containing 5-10
structures. Their similarity indicated that the tight and loose lamellae in these
two types of corpuscles corresponded to typical immature and mature corpuscles,
respectively, usually distributed along the palmar digital nerve. However,
mature, large corpuscles were absent from the nail bed, and most aberrant
corpuscles were smaller than typical corpuscles along the nerve. The aberrant
corpuscles were apparently incorporated into the tendon sheath or nail bed during
fetal vascular development, but they appeared to degenerate after birth due to
mechanical stress from the tendon or nail.
PMID- 28417054
TI - Three-dimensional and topographic relationships between the orbital margins with
reference to assessment of eyeball protrusion.
AB - This study investigated the topographic relationships among the eyeball and four
orbital margins with the aim of identifying the correlation between orbital
geometry and eyeball protrusion in Koreans. Three-dimensional (3D) volume
rendering of the face was performed using serial computed-tomography images of
141 Koreans, and several landmarks on the bony orbit and the cornea were directly
marked on the 3D volumes. The anterior-posterior distances from the apex of the
cornea to each orbital margin and between the orbital margins were measured in
both eyes. The distances from the apex of the cornea to the superior, medial,
inferior, and lateral orbital margins were 5.8, 5.8, 12.0, and 17.9 mm,
respectively. Differences between sides were observed in all of the orbital
margins, and the distances from the apex of the cornea to the superior and
inferior orbital margins were significantly greater in females than in males. The
anterior-posterior distance between the superior and inferior orbital margins did
not differ significantly between males (6.3 mm) and females (6.2 mm). The data
obtained in this study will be useful when developing practical guidelines
applicable to forensic facial reconstruction and orbitofacial surgeries.
PMID- 28417055
TI - Potential involvement of glycogen synthase kinase (GSK)-3beta in a rat model of
multiple sclerosis: evidenced by lithium treatment.
AB - Glycogen synthase kinase (GSK)-3beta has been known as a pro-inflammatory
molecule in neuroinflammation. The involvement of GSK-3beta remains unsolved in
acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of
this study was to evaluate a potential role of GSK-3beta in central nervous
system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment
significantly delayed the onset of EAE paralysis and ameliorated its severity.
Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis
factor a but not that of interleukin 10. Western blot analysis showed that the
phosphorylation of GSK-3beta (p-GSK-3beta) and its upstream factor Akt was
significantly increased in the lithium-treated group. Immunohistochemical
examination revealed that lithium treatment also suppressed the activation of
ionized calcium binding protein-1-positive microglial cells and vascular cell
adhesion molecule-1 expression in the spinal cords of lithium-treated EAE rats.
These results demonstrate that lithium ameliorates clinical symptom of acute
monophasic rat EAE, and GSK-3 is a target for the suppression of acute
neuroinflammation as far as rat model of human CNS disease is involved.
PMID- 28417056
TI - Therapeutic effect of prostaglandin E1 in monocrotaline-induced pulmonary
arterial hypertension rats.
AB - Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease
characterized by sustained increase in pulmonary arterial pressure and excessive
thickening and remodeling of distal small pulmonary arteries. During disease
progression, PAH include increase in mean pulmonary arterial pressure, right
ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth
muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting
various pathways involved in PAH progression have been approved by the Food and
Drug Adminstration. However, many of the currently available anti-PAH drugs
suffer from a number of limitations, including short biological half-life, and
poor pulmonary selectivity. Prostaglandin E1 (PGE1) is a potent vasodilator with
selectivity toward pulmonary circulation when it is administered via the
pulmonary route. However, PGE1 has a very short half-life of 5-10 minutes.
Therefore, we hypothesized that long-term effect of PGE1 could reduce mal
adaptive structural remodeling of the lung and heart and prevent ventricular
arrhythmias in monocrotaline-induced rat model of PAH. Our results revealed that
PGE1 reduced ventricular hypertrophy, protein expressions of endothelin-1 and
endothelin receptor A, and the expression of fibrosis. These results support the
notion that PGE1 can improve the functional properties of RV, highlighting its
potential benefits for heart and lung impairment.
PMID- 28417057
TI - Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as
a potential of tumor marker.
AB - Prostate cancer is the most common cancer type in men and is the second cause of
death, due to cancer, in patients over 50, after lung cancer. Prostate specific
antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is
discovered in non-prostatic cancer tissues in men and women raising doubts about
its specificity for prostatic tissues. PSA exists in low serum level in healthy
men and in higher levels in many prostate disorders, including prostatitis and
prostate cancer. Thus, a supplementary tumor marker is needed to accurately
diagnose the cancer and to observe the patient after treatment. Recently, soluble
human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for
different cancer types, including colorectal, breast, lung, and ovary. The
present descriptive-experimental study was carried out including patients with
malignant prostate tumor, patients with benign prostate tumor, and a group of
health men as the control group, as judged by an oncologist as well as a
pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked
immunosorbent assay in each group. The data was then analyzed using one-way
ANOVA. P<=0.05 was considered as statistically significant. The results showed
that the mean of sHLA-G level was high in patients. Also, it was found that there
was a significant difference in sHLA serum level between the three groups. The
data revealed that sHLA-G can be a novel supplementary tumor marker in addition
to PSA to diagnose prostate cancer.
PMID- 28417058
TI - Recognition of a rare intrathoracic rib with computed tomography: a case report.
AB - One of the uncommon congenital variations is intrathoracic rib which a normal, a
bifid, or an accessory rib lies within the thoracic cavity that is founded
accidentally. Clinically, in most cases they are without symptoms; however, it
may cause intrathoracic problems therefore it is important for radiologists and
physicians to identify to prevent of excessive intervention and treatment during
imaging diagnostic techniques of thoracic problems. In this report, we provide
the case of a rare presentation of an intrathoracic rib in a 3-year-old boy
arising from the inferior portion of a second rib based on findings from computed
tomography. To our knowledge, this is only the second reported case of this type
of intrathoracic rib that demonstrated with computed tomography.
PMID- 28417059
TI - Susceptibility of Human Oral Squamous Cell Carcinoma (OSCC) H103 and H376 cell
lines to Retroviral OSKM mediated reprogramming.
AB - Although numbers of cancer cell lines have been shown to be successfully
reprogrammed into induced pluripotent stem cells (iPSCs), reprogramming Oral
Squamous Cell Carcinoma (OSCC) to pluripotency in relation to its cancer cell
type and the expression pattern of pluripotent genes under later passage remain
unexplored. In our study, we reprogrammed and characterised H103 and H376 oral
squamous carcinoma cells using retroviral OSKM mediated method. Reprogrammed
cells were characterized for their embryonic stem cells (ESCs) like morphology,
pluripotent gene expression via quantitative real-time polymerase chain reaction
(RT-qPCR), immunofluorescence staining, embryoid bodies (EB) formation and
directed differentiation capacity. Reprogrammed H103 (Rep-H103) exhibited similar
ESCs morphologies with flatten cells and clear borders on feeder layer.
Reprogrammed H376 (Rep-H376) did not show ESCs morphologies but grow with a
disorganized morphology. Critical pluripotency genes Oct4, Sox2 and Nanog were
expressed higher in Rep-H103 against the parental counterpart from passage 5 to
passage 10. As for Rep-H376, Nanog expression against its parental counterpart
showed a significant decrease at passage 5 and although increased in passage 10,
the level of expression was similar to the parental cells. Rep-H103 exhibited
pluripotent signals (Oct4, Sox2, Nanog and Tra-1-60) and could form EB with the
presence of three germ layers markers. Rep-H103 displayed differentiation
capacity into adipocytes and osteocytes. The OSCC cell line H103 which was able
to be reprogrammed into an iPSC like state showed high expression of Oct4, Sox2
and Nanog at late passage and may provide a potential iPSC model to study multi
stage oncogenesis in OSCC.
PMID- 28417060
TI - Burden and predictors of Staphylococcus aureus and S. pseudintermedius infections
among dogs presented at an academic veterinary hospital in South Africa (2007
2012).
AB - BACKGROUND: Staphylococci are commensals of the mucosal surface and skin of
humans and animals, but have been implicated in infections such as otitis
externa, pyoderma, urinary tract infections and post-surgical complications.
Laboratory records provide useful information to help investigate these
infections. Therefore, the objective of this study was to investigate the burdens
of these infections and use multinomial regression to examine the associations
between various Staphylococcus infections and demographic and temporal factors
among dogs admitted to an academic veterinary hospital in South Africa. METHODS:
Records of 1,497 clinical canine samples submitted to the bacteriology laboratory
at a veterinary academic hospital between 2007 and 2012 were included in this
study. Proportions of staphylococcal positive samples were calculated, and a
multinomial logistic regression model was used to identify predictors of
staphylococcal infections. RESULTS: Twenty-seven percent of the samples tested
positive for Staphylococcus spp. The species of Staphylococcus identified were S.
pseudintermedius (19.0%), S. aureus (3.8%), S. epidermidis (0.7%) and S. felis
(0.1%). The remaining 2.87% consisted of unspeciated Staphylococcus. Distribution
of the species by age of dog showed that S. pseudintermedius was the most common
(25.6%) in dogs aged 2-4 years while S. aureus was most frequent (6.3%) in dogs
aged 5-6 years. S. pseudintermedius (34.1%) and S. aureus (35.1%) were the most
frequently isolated species from skin samples. The results of the multivariable
multinomial logistic regression model identified specimen, year and age of the
dog as significant predictors of the risk of infection with Staphylococcus. There
was a significant temporal increase (RRR = 1.17; 95% CI [1.06-1.29]) in the
likelihood of a dog testing positive for S. pseudintermedius compared to testing
negative. Dogs <= 8 years of age were significantly more likely to test positive
for S. aureus than those >8 years of age. Similarly, dogs between 2-8 years of
age were significantly more likely to test positive for S. pseudintermedius than
those >8 years of age. In addition, dogs 2-4 years of age (RRR = 1.83; 1.09-3.06)
were significantly more likely to test positive for S. pseudintermedius compared
to those <2 years of age. The risk of infection with S. pseudintermedius or S.
aureus was significantly higher in ear canal and skin specimens compared to other
specimens. CONCLUSIONS: The findings suggest that S. pseudintermedius and S.
aureus were the most commonly isolated species from dogs presented at the study
hospital. Age of the dog and the location of infection were significant
predictors of infection with both Staphylococcus species investigated.
Significant increasing temporal trend was observed for S. pseudintermedius but
not S. aureus. This information is useful for guiding clinical decisions as well
as future research.
PMID- 28417061
TI - Rates of morphological evolution in Captorhinidae: an adaptive radiation of
Permian herbivores.
AB - The evolution of herbivory in early tetrapods was crucial in the establishment of
terrestrial ecosystems, although it is so far unclear what effect this innovation
had on the macro-evolutionary patterns observed within this clade. The clades
that entered this under-filled region of ecospace might be expected to have
experienced an "adaptive radiation": an increase in rates of morphological
evolution and speciation driven by the evolution of a key innovation. However
such inferences are often circumstantial, being based on the coincidence of a
rate shift with the origin of an evolutionary novelty. The conclusion of an
adaptive radiation may be made more robust by examining the pattern of the
evolutionary shift; if the evolutionary innovation coincides not only with a
shift in rates of morphological evolution, but specifically in the morphological
characteristics relevant to the ecological shift of interest, then one may more
plausibly infer a causal relationship between the two. Here I examine the impact
of diet evolution on rates of morphological change in one of the earliest
tetrapod clades to evolve high-fibre herbivory: Captorhinidae. Using a method of
calculating heterogeneity in rates of discrete character change across a
phylogeny, it is shown that a significant increase in rates of evolution
coincides with the transition to herbivory in captorhinids. The herbivorous
captorhinids also exhibit greater morphological disparity than their faunivorous
relatives, indicating more rapid exploration of new regions of morphospace. As
well as an increase in rates of evolution, there is a shift in the regions of the
skeleton undergoing the most change; the character changes in the herbivorous
lineages are concentrated in the mandible and dentition. The fact that the
increase in rates of evolution coincides with increased change in characters
relating to food acquisition provides stronger evidence for a causal relationship
between the herbivorous diet and the radiation event.
PMID- 28417062
TI - Community partnerships in healthy eating and lifestyle promotion: A network
analysis.
AB - Promoting healthy eating and lifestyles among populations with limited resources
is a complex undertaking that often requires strong partnerships between various
agencies. In local communities, these agencies are typically located in different
areas, serve diverse subgroups, and operate distinct programs, limiting their
communication and interactions with each other. This study assessed the network
of agencies in local communities that promote healthy eating and lifestyles among
populations with limited resources. Network surveys were administered in 2016
among 89 agencies located in 4 rural counties in Michigan that served limited
resource audiences. The agencies were categorized into 8 types: K-12 schools,
early childhood centers, emergency food providers, health-related agencies,
social resource centers, low-income/subsidized housing complexes, continuing
education organizations, and others. Network analysis was conducted to examine 4
network structures-communication, funding, cooperation, and collaboration
networks between agencies within each county. Agencies had a moderate level of
cooperation, but were only loosely connected in the other 3 networks, indicated
by low network density. Agencies in a network were decentralized rather than
centralized around a few influential agencies, indicated by low centralization.
There was evidence regarding homophily in a network, indicated by some
significant correlations within agencies of the same type. Agencies connected in
any one network were considerably more likely to be connected in all the other
networks as well. In conclusion, promoting healthy eating and lifestyles among
populations with limited resources warrants strong partnership between agencies
in communities. Network analysis serves as a useful tool to evaluate community
partnerships and facilitate coalition building.
PMID- 28417063
TI - Melanized fungus as an Epidural abscess: A diagnostic and therapeutic challenge.
AB - Curvularia a dematiaceous fungus is ubiquitously found in soil around the world.
We report an epidural abscess due to Curvularia lunata in a 48 years male farmer
who underwent decompressive laminectomy as primary modality of treatment followed
by isolation, identification and confirmation of the isolate from tissue by ITS
sequencing. Antifungal therapy with voriconazole and amphotericin B for 3 and 2
weeks respectively improved patient's condition and is presently on regular
follow up with no sequelae since last 7 months.
PMID- 28417064
TI - Adenocarcinoma of the lung presenting as thrombotic thrombocytopenic purpura.
AB - Acquired thrombotic thrombocytopenic purpura (TTP) usually presents as severe
microangiopathic hemolytic anemia (MAHA) and thrombocytopenia in a previously
healthy individual. It occurs in approximately three in one million adults and 1
in 10 million children annually. The incidence is increased in females and
blacks. Diagnosing TTP and initiating therapy with plasma exchange is a must to
avoid preventable complications. Acquired thromotic microangiopathy has been
linked to collagen vascular diseases, use of certain medications, organ
transplants, infections, pregnancy and cancer. We report a rare case of a 56-year
old African American male diagnosed with TTP who found to have an asymptomatic
adenocarcinoma of the lung. Prompt cancer management resulted in completed
remission of the thrombotic microangiopathy.
PMID- 28417065
TI - Progressive dyspnea due to pulmonary carcinoid tumorlets.
AB - This is a case description of a female patient, 77 years-old, who presented with
progressive dyspnea and cough. She had a mild hypoxemia in the arterial blood
gases (PaO2 72 mmHg) and normal spirometry. The chest computer tomography
revealed diffuse "ground glass" opacities, segmental alveolitis, bronchiectasis,
fibrotic lesions and numerous micronodules. A thoracoscopy was performed and the
obtained biopsy showed carcinoid tumorlets, with positive CK8/18, CD56, TTF-1 and
synaptophysin immunohistochemical markers. Pulmonary carcinoid tumorlets are
rare, benign lesions and individuals with tumorlets are typically asymptomatic.
Our report presents a symptomatic clinical case of carcinoid tumorlet.
PMID- 28417066
TI - Ezogabine skin discoloration is reversible after discontinuation.
AB - There is concern that bluish skin discoloration associated with ezogabine
treatment could be permanent. We present a case of ezogabine-induced skin
discoloration that resolved completely after discontinuation. A 55-year-old woman
started ezogabine 400 mg three times a day at age 41. Bluish pigmentation over
the toe nails, finger nails, around eyes and over and around lips was first noted
after 5 years of treatment. Ezogabine was discontinued eight years after
initiation. Skin discoloration improved within 6 months and completely resolved
within 6 years of discontinuation. This case suggests that ezogabine-induced
discoloration is reversible after discontinuation of treatment.
PMID- 28417067
TI - Quantitative photoacoustic integrating sphere (QPAIS) platform for absorption
coefficient and Gruneisen parameter measurements: Demonstration with human blood.
AB - Quantitative photoacoustic imaging in biomedicine relies on accurate measurements
of relevant material properties of target absorbers. Here, we present a method
for simultaneous measurements of the absorption coefficient and Gruneisen
parameter of small volume of liquid scattering and absorbing media using a
coupled-integrating sphere system which we refer to as quantitative photoacoustic
integrating sphere (QPAIS) platform. The derived equations do not require
absolute magnitudes of optical energy and pressure values, only calibration of
the setup using aqueous ink dilutions is necessary. As a demonstration,
measurements with blood samples from various human donors are done at room and
body temperatures using an incubator. Measured absorption coefficient values are
consistent with known oxygen saturation dependence of blood absorption at 750 nm,
whereas measured Gruneisen parameter values indicate variability among five
different donors. An increasing Gruneisen parameter value with both hematocrit
and temperature is observed. These observations are consistent with those
reported in literature.
PMID- 28417068
TI - Photoacoustic in vitro flow cytometry for nanomaterial research.
AB - Conventional flow cytometry is a versatile tool for drug research and cell
characterization. However, it is poorly suited for quantification of non
fluorescent proteins and artificial nanomaterials without the use of additional
labeling. The rapid growth of biomedical applications for small non-fluorescent
nanoparticles (NPs) for drug delivery and contrast and therapy enhancement, as
well as research focused on natural cell pigments and chromophores, demands high
throughput quantification methods for the non-fluorescent components. In this
work, we present a novel photoacoustic (PA) fluorescence flow cytometry (PAFFC)
platform that combines NP quantification though PA detection with conventional in
vitro flow cytometry sample characterization using fluorescence labeling. PAFFC
simplifies high-throughput analysis of cell-NP interactions, optimization of
targeted nanodrugs, and NP toxicity assessment, providing a direct correlation
between NP uptake and characterization of toxicity markers for every cell.
PMID- 28417070
TI - Acute bacteremic pneumonia due to melioidosis developing in the intensive care
setting.
AB - In Malaysia, melioidosis is commonly encountered as this infection is known as
part of the endemic area for the disease. Managing cases of positive Burkholderia
pseudomallei infection can involve multidisciplinary unit mainly, microbiologist,
infectious disease team and intensive care as it may be quite difficult to
distinguish melioidosis from a number of other diseases on the clinical setting
alone. Laboratory diagnosis plays a vital role in determining the direction of
management. Investigations such as culture, polymerase chain reaction (PCR) and
serology should be evaluated once the disease is suspected. In this particular
case, the patient is a young adult involved in a road traffic accident. Unlike
any other cases with melioidosis, he had no potential risk factors which may have
contributed to the severity of the disease and it is likely that the site of the
accident was the source of acquisition of this gram negative bacterium.
PMID- 28417069
TI - Clostridium difficile bacteremia: Report of two cases in French hospitals and
comprehensive review of the literature.
AB - We report two cases of bacteremia due to Clostridium difficile from two French
hospitals. The first patient with previously diagnosed rectal carcinoma underwent
courses of chemotherapy, and antimicrobial treatment, and survived the C.
difficile bacteremia. The second patient with colon perforation and newly
diagnosed lung cancer underwent antimicrobial treatment in an ICU but died
shortly after the episode of C. difficile bacteremia. A review of the literature
allowed the identification of 137 cases of bacteremia between July 1962 and
November 2016. Advanced age, gastro-intestinal disruption, severe underlying
diseases and antimicrobial exposure were the major risk factors for C. difficile
bacteremia. Antimicrobial therapy was primarily based on metronidazole and/or
vancomycin. The crude mortality rate was 35% (21/60).
PMID- 28417071
TI - Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi
Arabian patients with maple syrup urine disease.
AB - Maple syrup urine disease (MSUD), an autosomal recessive inborn error of
metabolism due to defects in the branched-chain alpha-ketoacid dehydrogenase
(BCKD) complex, is commonly observed among other inherited metabolic disorders in
the kingdom of Saudi Arabia. This report presents the results of mutation
analysis of three of the four genes encoding the BCKD complex in 52 biochemically
diagnosed MSUD patients originating from Saudi Arabia. The 25 mutations (20
novel) detected spanned across the entire coding regions of the BCKHDA, BCKDHB
and DBT genes. There were no mutations found in the DLD gene in this cohort of
patients. Prediction effects, conservation and modelling of novel mutations
demonstrated that all were predicted to be disease-causing. All mutations
presented in a homozygous form and we did not detect the presence of a "founder"
mutation in any of three genes. In addition, prenatal molecular genetic testing
was successfully carried out on chorionic villus samples or amniocenteses in 10
expectant mothers with affected children with MSUD, molecularly characterized by
this study.
PMID- 28417072
TI - Atypical juvenile presentation of GM2 gangliosidosis AB in a patient compound
heterozygote for c.259G > T and c.164C > T mutations in the GM2A gene.
AB - GM2-gangliosidosis, AB variant is an extremely rare autosomal recessive inherited
disorder caused by mutations in the GM2A gene that encodes GM2 ganglioside
activator protein (GM2AP). GM2AP is necessary for solubilisation of GM2
ganglioside in endolysosomes and its presentation to beta-hexosaminidase A.
Conversely GM2AP deficiency impairs lysosomal catabolism of GM2 ganglioside,
leading to its storage in cells and tissues. We describe a 9-year-old child with
an unusual juvenile clinical onset of GM2-gangliosidosis AB. At the age of 3
years he presented with global developmental delay, progressive epilepsy,
intellectual disability, axial hypertonia, spasticity, seizures and ataxia, but
without the macular cherry-red spots typical for GM2 gangliosidosis. Brain MRI
detected a rapid onset of diffuse atrophy, whereas whole exome sequencing showed
that the patient is a compound heterozygote for two mutations in GM2A: a novel
nonsense mutation, c.259G > T (p.E87X) and a missense mutation c.164C > T
(p.P55L) that was recently identified in homozygosity in patients of a Saudi
family with a progressive chorea-dementia syndrome. Western blot analysis showed
an absence of GM2AP in cultured fibroblasts from the patient, suggesting that
both mutations interfere with the synthesis and/or folding of the protein.
Finally, impaired catabolism of GM2 ganglioside in the patient's fibroblasts was
demonstrated by metabolic labeling with fluorescently labeled GM1 ganglioside and
by immunohistochemistry with anti-GM2 and anti-GM3 antibodies. Our observation
expands the molecular and clinical spectrum of molecular defects linked to GM2
gangliosidosis and suggests novel diagnostic approach by whole exome sequencing
and perhaps ganglioside analysis in cultured patient's cells.
PMID- 28417073
TI - Primary Amyloidosis of the Urinary Bladder: A Case Report.
AB - Primary amyloidosis of the urinary bladder is a rare disease, with only
approximately 200 cases reported in the literature. We herein present a case of
amyloidosis of the urinary bladder with painful gross hematuria. Pelvic Computed
Tomography showed uneven thickening of the bladder wall suspicious of neoplastic
lesion. Cystoscopy and transurethral resection were performed. Congo-red staining
confirmed amyloidosis it was. Postoperative recovery was good and close follow-up
was recommended after discharged. Amyloidosis is usually benign, while it can
masquerade as a malignancy. Doctors should consider it when imaging studies
reveal a malignancy in bladder.
PMID- 28417074
TI - Renal Leiomyoma: A Case Report and Review of the Literature.
AB - Leiomyoma is an uncommon tumor of the kidney. The authors report a rare case of
renal leiomyoma in a 39-year-old male patient who presented with a right flank
mass. Laparoscopic nephrectomy was performed. The histopathology and
immunohistochemistry confirm the diagnosis of renal leiomyoma. The review of
literature in the clinicoradiopathological correlation was illustrated.
PMID- 28417075
TI - Giant Ureteral Fibroepithelial Polyp with Intermittent Prolapse Reaching the
Urethral Meatus: A Case Report.
AB - Ureteral fibroepithelial polyps (UFPs) are rare non-epithelial benign tumors of
the urinary tract. Treatment of such cases ranges from conservative management to
surgical resection of the polyp. Hereby, we present a rare case of a 37-year-old
female patient with giant 14 cm UFP of the distal left ureter, successfully
resected by ureteroscopic electrocauterization. Several cases of UFPs have been
previously reported in world literature describing polyps extending into the
bladder; yet, our case is the first to present a giant UFP that extends beyond
the bladder cavity protruding outside the urethral meatus as a red fleshy mass.
PMID- 28417076
TI - The Case of Huge Pure Lipoma of the Spermatic Cord Misdiagnosed as Inguinal
Hernia.
AB - Clinically, pure spermatic-cord lipoma has not been recognized as a disease
entity but regarded as an incidental finding at the time of hernia repair,
because it presents groin symptoms and clinical findings indistinguishable from
those of inguinal hernia. We report the successful treatment of case of huge pure
spermatic-cord lipoma originally misdiagnosed as inguinal hernia. The patients
had tumor excision without orchiectomy. Symptoms improved without any
complication. In patients with inguinal hernia symptoms, pure spermatic-cord
lipoma should be recognized as a significant clinical entity, and differential
diagnosis should be achieved using ultrasonography and computed tomography to
avoid unnecessary hernia repair.
PMID- 28417077
TI - Direct Extension of Prostatic Adenocarcinoma Protruding Through the Urethral
Meatus.
AB - Prostate cancer involving the anterior urethra is rare with few cases describing
isolated recurrence to the anterior urethra. This case describes a patient with a
history of metastatic prostate cancer who subsequently developed advanced
prostate cancer involving the entire urethra with extension from the prostatic
urethra to the urethral meatus. This will help future healthcare providers
recognize this metastatic pattern as a possibility and explore this option when
presented with a bleeding mass at the urethral meatus of unknown origin. It is
important for clinicians to realize poorly differentiated prostate cancer may not
produce PSA yet still behave aggressively.
PMID- 28417078
TI - Local Excision for the Treatment of Penile Verrucous Carcinoma.
AB - Penile verrucous carcinoma is known for its favorable biologic behavior and lack
of metastatic potential. For preservation of function, treatment has been focused
on partial penectomy. Despite partial penectomy for preservation of minimal
functional and aesthetic aspects, patients have experienced psychosexual
problems. A 73-year-old man had a cauliflower-like verrucous carcinoma on the
penile glans and coronary sulcus diagnosed by using excisional biopsy. He
underwent degloving excision to save the penile shaft and glans penis. Surgical
margin was 3 mm. He had been tumor-free at the 2-year follow-up. For maximum
preservation of the functional and aesthetic aspects, we recommend degloving
excision.
PMID- 28417079
TI - Detection of copy number alterations in cell-free tumor DNA from plasma.
AB - BACKGROUND: Somatic copy number alterations (SCNAs) occurring in tumors can
provide information about tumor classification, patient's outcome or treatment
targets. Liquid biopsies, incl. plasma samples containing circulating cell-free
tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however
specify and reliability of methods have to be tested. METHODS: SNP microarrays
(Affymetrix) were used to generate whole-genome copy number profiles from plasma
ccfDNA (OncoScan) and paired tumor biopsies (CytoScan) from ten patients with
metastatic cancers. Numerical, segmental and focal SCNAs were assessed using
ASCAT/TuScan and SNP-FASST2. RESULTS: Aberrations in ccfDNA in 4 patients
resembled numerical (76%) and segmental (80%) aberrations in tDNA. Three patients
represented low correlation due to postponed sampling time, ccfDNA quality and
possible treatment interference. Breakpoints of high-amplitude amplification were
assessed with high accuracy and relative breakpoints difference of only 7% (0.02
37%). Similarly, biallelic losses were reliably detected. Array was 100%
successful in detection of SCNAs on clinically relevant genes compared to SCNAs
in tumor biopsies. Tracking of SCNAs changes during the treatment course of one
patient also indicated that apoptosis/necrosis of non-cancerous cells presumably
induced by treatment can influence ccfDNA composition and introduce false
negative findings into the analysis of liquid biopsies. CONCLUSIONS: Genomic
alterations detected in ccfDNA from liquid biopsies by comprehensive SNP array
are reliable source for information for stratification of patients for targeted
treatment. GENERAL SIGNIFICANCE: Clinically relevant SCNAs can be detected in
ccfDNA with high resolution and can therefore serve as an alternative to tumor
biopsy in defining treatment targets.
PMID- 28417081
TI - An ELISA protocol to improve the accuracy and reliability of serological antibody
assays.
AB - To assay serum antibodies by indirect ELISA, it is critical to eliminate a
variety of false positive and negative reactions attributed to the principle.
These include 1) the background (BG) noise reaction caused by hydrophobic binding
of immunoglobulin components in sample specimens to solid surfaces, 2) false
positive reaction caused by non-specific binding of immunoglobulins to target
antigens by protein-protein interactions, and 3) other false positive and
negative reactions caused by buffer components. No current blocking agents can
prevent these false positive and negative reactions, and antibody assay results
vary significantly depending on the buffer system used. To address these
fundamental problems, we investigated all types of non-specific reactions
involved in indirect ELISAs, and the blocking efficacy of current buffer systems
and a newly developed ELISA buffer, ChonBlockTM. The accuracy and reliability of
these assay results were examined in detail by inhibition tests in individual
buffer systems. Based on these studies, we are providing a definitive ELISA
protocol for all users to improve ELISA technique and obtain accurate, reliable,
and reproducible assay data against a variety of antigens.
PMID- 28417082
TI - Improving glucose tolerance by muscle-damaging exercise.
AB - : Tissue damage is regarded as an unwanted medical condition to be avoided.
However, introducing tolerable tissue damages has been used as a therapeutic
intervention in traditional and complementary medicine to cure discomfort and
illness. Eccentric exercise is known to cause significant necrosis and insulin
resistance of skeletal muscle. The purpose of this study was to determine the
magnitude of muscle damage and blood glucose responses during an oral glucose
tolerance test (OGTT) after eccentric training in 21 young participants. They
were challenged by 5 times of 100-meter downhill sprinting and 20 times of squats
training at 30 pounds weight load for 3 days, which resulted in a wide spectrum
of muscle creatine kinase (CK) surges in plasma, 48 h after the last bout of
exercise. Participants were then divided into two groups according the magnitude
of CK increases (low CK: +48% +/- 0.3; high CK: +137% +/- 0.5, P < 0.05). Both
groups show comparable decreases in blood glucose levels in OGTT, suggesting that
this muscle-damaging exercise does not appear to decrease but rather improve
glycemic control in men. CONCLUSION: The result of the study rejects the
hypothesis that eccentric exercise decreases glucose tolerance. Improved glucose
tolerance with CK increase implicates a beneficial effect of replacing
metabolically weaker muscle fibers by eccentric exercise in Darwinian natural
selection fashion.
PMID- 28417080
TI - Applying a systems approach to thyroid physiology: Looking at the whole with a
mitochondrial perspective instead of judging single TSH values or why we should
know more about mitochondria to understand metabolism.
AB - : Classical thinking in endocrine physiology squeezes our diagnostic handling
into a simple negative feedback mechanism with a controller and a controlled
variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4,
respectively. The setting of this tight notion has no free space for any
additions. In this paper we want to challenge this model of limited application
by proposing a construct based on a systems approach departing from two basic
considerations. In first place since the majority of cases of thyroid disease
develop and appear during life it has to be considered as an acquired condition.
In the second place, our experience with the reversibility of morphological
changes makes the autoimmune theory inconsistent. While medical complexity can
expand into the era of OMICS as well as into one where manipulations with the use
of knock-outs and -ins are common in science, we have preferred to maintain a
simple and practical approach. We will describe the interactions of iron,
magnesium, zinc, selenium and coenzyme Q10 with the thyroid axis. The discourse
will be then brought into the context of ovarian function, i.e. steroid hormone
production. Finally the same elemental players will be presented in relation to
the basic mitochondrial machinery that supports the endocrine. We propose that an
intact mitochondrial function can guard the normal endocrine function of both the
thyroid as well as of the ovarian axis. The basic elements required for this
function appear to be magnesium and iron. In the case of the thyroid, magnesium
ATP acts in iodine uptake and the heme protein peroxidase in thyroid hormone
synthesis. A similar biochemical process is found in steroid synthesis with
cholesterol uptake being the initial energy-dependent step and later the heme
protein ferredoxin 1 which is required for steroid synthesis. Magnesium plays a
central role in determining the clinical picture associated with thyroid disease
and is also involved in maintaining fertility. With the aid of 3D sonography
patients needing selenium and/or coenzyme Q10 can be easily identified. By this
we firmly believe that physicians should know more about basic biochemistry and
the way it fits into mitochondrial function in order to understand metabolism.
Contemplating only TSH is highly reductionistic. OUTLINE: *Author's profiles and
motivation for this analysis*The philosophical alternatives in science and
medicine*Reductionism vs. systems approach in clinical thyroid disease
guidelines*The entry into complexity: the involvement of the musculoskeletal
system*Integrating East and West: teachings from Chinese Medicine and from
evidence based medicine (EBM)*Can a mathematical model represent complexity in
the daily thyroid practice?*How effective is thyroxine treatment?*Resolving the
situation of residual symptoms in treated patients with thyroid
disease*Importance of iron, zinc and magnesium in relation to thyroid
function*Putting together new concepts related to thyroid function for a systems
approach*Expanding our model into general aspects of medicine.
PMID- 28417083
TI - Effects of turmeric curcuminoids and metformin against central sensitivity to
pain in mice.
AB - The reported experimental study was conducted to compare the effects of repeated
daily oral doses of curcuminoids (CLE) with metformin as potential
antidepressants and analgesics. Effects of a single and ten daily oral doses of
CLE (5, 20, 80 mg/kg/day) and of 50 mg/kg/day metformin (MET) were compared in
mice hot plate test (HPT) for analgesics. On the 11th treatment day, all animals
were subjected to foot shock stress triggered hyperthermia test, and on the 12th
treatment day to tail suspension test (TST) for antidepressants. Immediately
thereafter, their blood levels of glucose, insulin and cortisol were quantified.
Dose dependent analgesic activity of CLE was observed in HPT, whereas the
metformin dose tested suppressed only pain hypersensitivity in the test. But
statistically significant effects of both of them were observed in TST, and both
of them also afforded protections against body weight loss and slight elevation
in core temperatures induced by daily handling and repeated testing. CLE or
metformin had no significant effects in foot shock stress triggered transient
hyperthermic responses or on blood glucose, insulin and cortisol levels. Reported
results reveal that curcuminoids as well as metformin are stress response
modifiers with antidepressants like activities, but only low dose curcuminoids
possess centrally acting analgesics like activities. They suggest that the bio
assay system used in this study is well suited for identifying curcuminoids like
plant metabolites with analgesic and anti-stress activities, and that low dose
curcuminoids are more effective as analgesics than low dose metformin.
PMID- 28417084
TI - Antioxidant, antimicrobial activity and bioactive compounds of Bergenia ciliata
Sternb.: A valuable medicinal herb of Sikkim Himalaya.
AB - Bergenia ciliata Sternb., commonly known as Paashaanbhed, is a well known herb of
Sikkim Himalaya with various pharmaceutical properties. However, scientific
exploration of B. ciliata, growing in the Sikkim Himalaya, for phytochemicals and
pharmacological properties is in infancy. With this view, the present study was
undertaken to investigate B. ciliata leaf extracts for antioxidant, antimicrobial
activity and bioactive compounds. Three solvents viz., methanol, ethyl acetate
and hexane were used for extraction and the respective leaf extracts were
analyzed for total phenolic and flavonoid contents along with the antioxidant and
antimicrobial activities. Amongst the tested solvents, methanol was found to be
the best solvent for extraction with highest total phenolic contents and the
lowest IC50 values for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino
bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Methanol extract also
exhibited effective antimicrobial activity, particularly against bacteria and
actinomycetes. Further, high performance liquid chromatography (HPLC) analysis
revealed that methanolic extract contains the highest amount of all the three
analyzed bioactive compounds viz. bergenin, catechin and gallic acid. The current
study suggests that the methanol extract of B. ciliata is a potential source of
natural antioxidant and antimicrobial compounds that can be used in food and drug
industries.
PMID- 28417085
TI - Hepatoprotective standardized EtOH-water extract from the seeds of Fraxinus
rhynchophylla Hance.
AB - Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex
fraxini ( qin pi) listed in Chinese Pharmacopoeia. Phytochemical study has
indicated that methanol extracts from Qinpi has protective effect on acute liver
injury. The present study investigates the hepatoprotective activity of EtOH
water extract from the seeds of F. rhynchophylla Hance against carbon
tetrachloride-induced liver injury in mice. The EtOH-water extract significantly
alleviated liver damage as indicated by the decreased levels of serum alanine
aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde
(MDA) content, and increased the levels of superoxide dismutase (SOD),
glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the
pathological tissue injury induced by CCl4. Quantitative analysis of seven major
constituents (1-7) in EtOH-water extract (EWE) was developed by high performance
liquid chromatography-diode-array detector (HPLC-DAD). The current research
indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver
index, inhibited the increase of serum aminotransferase induced by CCl4, and
decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested
that the pretreatment with EWE protected mice against CCl4-induced liver
injuries. Based on the results, the EtOH-water extract from the seeds of F.
rhynchophylla Hance is efficacious for prevention and treatment of CCl4-induced
hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active
ingredients responsible for the biological and pharmacological activities of
hepatoprotection.
PMID- 28417086
TI - Blood immune function parameters in response to combined aerobic dance exercise
and honey supplementation in adult women.
AB - To date, information on the effectiveness of combined aerobic dance exercise with
honey supplementation on immune function in women is lacking. The present study
investigated the effects of 8 weeks of combined aerobic dance exercise and honey
supplementation on blood immune function parameters in adult women. In this
study, forty four healthy sedentary women (25-40 year-old) were assigned into
four groups with n = 11 per group: sedentary without supplementation control
(Con), honey supplementation (H), aerobic dance exercise (D) and combined aerobic
dance exercise with honey supplementation (HD) groups. Aerobic dance exercise was
carried out for one hour per session, three sessions per week for eight weeks.
Honey drink was consumed by H and HD groups, in a dosage of 20 g of honey diluted
in 300 ml of plain water, consumed 7 days a week for 8 weeks. In HD group, the
participants were required to consume honey drink 30 min before performing
exercise. Before and after 8 weeks of experimental period, blood samples were
taken to determine the concentrations of immune parameters which include full
blood counts and immunophenotyping measurements. It was found that after 8 weeks
of experimental period, there were statistically significant increases in T
cytotoxic (CD8) (p < 0.05) in HD group. Additionally, the percentages increase in
total lymphocyte counts, T helper (CD4), and T cytotoxic (CD8) counts after 8
weeks were the highest in HD group among all the groups. As conclusion, combined
aerobic dance and honey supplementation may have potential to enhance immune
functions in women.
PMID- 28417087
TI - Screening for antibacterial and antibiofilm activity in Thai medicinal plant
extracts against oral microorganisms.
AB - To evaluate the antibacterial activity of 12 ethanol extracts of Thai traditional
herb against oral pathogens. The antibacterial activities were assessed by agar
well diffusion, broth microdilution, and time-kill methods. Antibiofilm activity
was investigated using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium
bromide (MTT) assay. High performance liquid chromatography (HPLC), thin layer
chromatography (TLC) fingerprinting, and TLC-bioautography were used to determine
the active antibacterial compounds. Piper betle showed the best antibacterial
activities against all tested strains in the minimal inhibitory concentration and
minimal bactericidal concentration, ranged from 1.04-5.21 mg/mL and 2.08-8.33
mg/mL, respectively. Killing ability depended on time and concentrations of the
extract. P. betle extract acts as a potent antibiofilm agent with dual actions,
preventing and eradicating the biofilm. The major constituent of P. betle extract
was 4-chromanol, which responded for antibacteria and antibiofilm against oral
pathogens. It suggests that the ethanol P. betle leaves extract may be used for
preventing oral diseases.
PMID- 28417088
TI - Boiling-induced nanoparticles and their constitutive proteins from Isatis
indigotica Fort. root decoction: Purification and identification.
AB - Colloidal particles are essential components of sun-dried Isatis indigotica Fort.
roots (Ban-Lan-Gen in Chinese, BLG) decoction. Nanoparticles (NPs) were isolated
from BLG decoction with size exclusion chromatography and characterized. Their
average diameter is ~120 nm, reversibly responding to pH and temperature changes.
They promoted the growth of normal cells but suppressed that of cancerogenic
cells and macrophages. Two constitutive glycated proteins were identified from
the NPs, namely BLGP1 and BLGP2. Their N-terminal amino acid sequences were V-X-R
E-V-V-K-D-I and V-V-R-E-V-V-K-D-I-A-G-A-V-Q-T-N-E-Q-Y. Their full-length cDNA
sequences were cloned to obtain the highly homological amino acid sequences of
non-glycated proteins, whose theoretical molecular weights are 21831.64 Da and
21841.67 Da. Using pepsin hydrolysis and mass spectrometry, four possible
glycation adducts were identified in BLGP1, whereas one in BLGP2. To conclude,
bioactive nanoparticles isolated from the herbal decoction are intelligent
nanoassemblies composed of a new boiling-stable protein. Glycation plays a
critical role in heat-induced formation of these nanoassemblies. The novel,
intelligent, safe and stable nano-carriers for drug delivery may be developed
using BLG NPs as prototype.
PMID- 28417089
TI - Demographic and medication characteristics of traditional Chinese medicine users
among colorectal cancer survivors: A nationwide database study in Taiwan.
AB - Chinese herbal product (CHP) is the major type of traditional Chinese medicine
(TCM) and widely used to relief the symptom of colorectal cancer. The aim of the
study was to analyze the utilization of CHP for treating patients with colorectal
cancer in Taiwan. The usage of CHP, frequency of services, and prescription
pattern for colorectal cancer were analyzed from a randomly sampled cohort of 1
million beneficiaries from the National Health Insurance Research Database. The
odds ratios for utilization of CHP were estimated with logistic regression model.
2846 patients were newly diagnosed as colorectal cancer during 1998-2008 in the
million cohort in Taiwan. 42.7% (n = 1214) of them used CHP. Colorectal cancer
was the most common diagnosis coded by TCM doctor, followed by symptoms, signs,
and ill-defined conditions. Costusroot and Amomum Six Gentlemen Decoction ( xiang
sha liu jun zi tang) was the most frequently prescribed formula for treating
colorectal cancer. Among the top 10 most frequently prescribed CHP for treating
colorectal cancer, six containing Ginseng Radix (, Panax ginseng) and two
containing Astragali Radix (, Astragalus membranaceus), which are reported to
have potential beneficial synergistic effects on colorectal cancer cells. CHP
containing Ginseng Radix or Astragali Radix are the most frequently prescribed
for colorectal cancer and their effects should be taken into account by
healthcare providers.
PMID- 28417092
TI - Revival, modernization and integration of Indian traditional herbal medicine in
clinical practice: Importance, challenges and future.
AB - In spite of incredible advances in modern science, technology and allopathic
medicine a large we are unable to provide quality healthcare to all. Traditional
medicine particularly herbal medicine considered as a major healthcare provider
around the globe particularly in rural and remote areas. A large section of
people depends on such medicine for their primary healthcare mainly in
underdeveloped or developing countries. Indian traditional medicinal system like
Ayurveda, Siddha and Unani has a very rich history of their effectiveness; modern
research also acknowledged the importance of such medicine. Indian traditional
medicine or medicinal plants are also considered as a vital source of new drug.
Mainstreaming of such medicine is important for the people. Several steps have
been taken in India to promote such medicine and to integrate them into clinical
practice. Evidence based incorporation of Indian traditional medicine in clinical
practice will help to provide quality healthcare to all.
PMID- 28417090
TI - Role of traditional Islamic and Arabic plants in cancer therapy.
AB - ETHNO PHARMACOLOGICAL RELEVANCE: This review article underlines individual
Traditional Islamic and Arabic plant (TAI) and their role in treating cancer. The
aim of the study is to specifically evaluate the progress of herbs, Arabic and
Islamic traditional herbs in particular, applied in cancer treatment, so far.
MATERIALS AND METHODS: Islamic and Arabic plants were selected and identified
through different literature survey using "Google scholar", "Web of science",
"Scopus" and "PubMed". Each plant, from identified Arabic and Islamic plants
list, was search individually for the most cited articles in the aforementioned
databases using the keywords, "Anticancer", "Uses in cancer treatment", "Ethno
pharmacological importance in cancer" etc. RESULTS: The current review about
Islamic and Arabic plants illuminates the importance of Islamic and Arabic plants
and their impact in treating cancer. There is a long list of Islamic and Arabic
plants used in cancer as mentioned in review with enormous amount of literature.
Each plant has been investigated for its anticancer potential. The literature
survey as mentioned in table shows; these plants are widely utilized in cancer as
a whole, a part thereof or in the form of isolated chemical constituent.
CONCLUSIONS: This review strongly supports the fact; Arabic and Islamic
traditional plants have emerged as a good source of complementary and alternative
medicine in treating cancer. Traditional Arab-Islamic herbal-based medicines
might be promising for new cancer therapeutics with low toxicity and minimal side
effects. The plants used are mostly in crude form and still needs advance
research for the isolation of phytochemicals and establishing its cellular and
molecular role in treating cancer.
PMID- 28417091
TI - Biological activities of curcuminoids, other biomolecules from turmeric and their
derivatives - A review.
AB - In recent years, several drugs have been developed deriving from traditional
products and current drug research is actively investigating the possible
therapeutic roles of many Ayruvedic and Traditional Indian medicinal therapies.
Among those being investigated is Turmeric. Its most important active ingredient
is curcuminoids. Curcuminoids are phenolic compounds commonly used as a spice,
pigment and additive also utilized as a therapeutic agent used in several foods.
Comprehensive research over the last century has revealed several important
functions of curcuminoids. Various preclinical cell culture and animals studies
suggest that curcuminoids have extensive biological activity as an antioxidant,
neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective
and arthritis. Different clinical trials also suggest a potential therapeutic
role for curcuminoids in numerous chronic diseases such as colon cancer, lung
cancer, breast cancer, inflammatory bowel diseases. The aim of this review is to
summarize the chemistry, analog, metal complex, formulations of curcuminoids and
their biological activities.
PMID- 28417093
TI - Instability resistance training for health and performance.
AB - Recently, resistance exercises performed on an unstable surface have become part
of athletic training and rehabilitation. Accordingly, their role in performance
and health-oriented strength training has increasingly emerged as a matter of
interest to researchers and conditioning specialists. A more pronounced
activation of stabilizing muscles is assumed to be the main feature of
instability resistance exercises. This assumption has been proven by EMG studies,
which have highlighted significantly greater electromyographic activity of trunk
stabilizing muscles during exercises under unstable as compared to stable
conditions. Intervention studies also demonstrated an enhanced improvement of
trunk stability after training programs utilizing unstable devices as compared to
floor exercises. Findings indicate that instability resistance training may
facilitate the neural adaptation of trunk-stabilizing muscles, resulting in an
improvement in trunk stability. However, both acute and long-term responses of
primarily activated muscles to exercises performed on an unstable surface remain
a matter of debate. It has been established that there is a significantly lower
peak isometric force and rate of force development during resistance exercises
under unstable as compared to stable conditions. In addition, the power output
was compromised when exercises were performed on unstable surfaces. However, we
have demonstrated that this effect depends on the type of exercise, instability
device used, weight lifted, subject's training background, and so forth. Our
findings on muscular power in the concentric phase of resistance exercises with
different weights under stable and unstable conditions complement this review.
Applications of instability resistance exercises for the improvement of
neuromuscular functions in the physically active, plus for those following
anterior cruciate ligament reconstructions, are also presented.
PMID- 28417095
TI - A visual grid to digitally record an Ayurvedic Prakriti assessment; a first step
toward integrated electronic health records.
PMID- 28417096
TI - Regulation of herbal medicine use based on speculation? A case from Sri Lanka.
AB - Chronic Kidney Disease of Unknown aetiology is a significant public health
problem in Sri Lanka. The final report by the WHO mission recommended regulation
of herbal medicines containing aristolochic acid, which is an established
nephrotoxin. The use of Complimentary and Alternative Medicine (CAM) has a
history of more than 2500 years in Sri Lanka. Aristolochia species are rarely
used in Ayurveda and traditional medicine in Sri Lanka. Before regulating the
analysis of herbal preparations using Aristolochia, collecting data from CAM
practitioners regarding the use of Aristolochia is necessary. Analysis of
Ayurveda pharmacopeia shows the doses used are negligible and some preparations
are used for external applications.
PMID- 28417097
TI - Zika-related microcephaly in experimental models.
PMID- 28417094
TI - Contemporary acupressure therapy: Adroit cure for painless recovery of
therapeutic ailments.
AB - Since time immemorial, complementary and alternative medicines (CAM) have played
a significant role in human health care. CAM is known to have a strong reputation
and reliability within every culture to provide basic health care treatment for
patients. CAM acts as a better therapeutic option in human being for treating
various diseases and improving quality of life with apt consideration to the
economic aspects. Acupressure, one of the known CAM, originated in ancient China
is based on the principal of acupoints activation across the meridians which
correct the imbalance between Qi. Activation of specific points on the meridians
is known to facilitate reduction of pain at the local sites. It also reduces the
pain from other body parts. This review outlines various types, devices and
mechanisms involved in the acupressure treatment.
PMID- 28417098
TI - Avoiding apoptosis during mammalian hibernation.
PMID- 28417099
TI - Data for transcriptomic and proteomic analyses of leaves from Clematis terniflora
DC. under binary stress.
AB - High level of UV-B irradiation followed by dark treatment accumulates secondary
metabolites in Clematis terniflora DC. To investigate the response mechanism
under high level of UV-B irradiation followed by dark treatment, transcriptomic
and proteomic analyses were performed in leaves of Clematis terniflora DC. The
experimental design for the transcriptomic and proteomic analyses in leaves of C.
terniflora under stresses was organized into a picture. For transcriptomics, mRNA
sequencing technology was used. Genes identified in leaves of C. terniflora at
starting point, high level of UV-B irradiation, and high level of UV-B
irradiation followed by dark treatment were listed; genes with different
expression levels at starting point, high level of UV-B irradiation, and high
level of UV-B irradiation followed by dark treatment were also presented in this
DiB article. For proteomics, a gel-free/label-free proteomic technique was used.
Proteins with different abundances in leaves at starting point, high level of UV
B irradiation, and high level of UV-B irradiation followed by dark treatment were
presented in this DiB article. In order to monitor the expression levels of genes
under the stress, quantitative reverse transcription polymerase chain reaction
was performed. The primer sequences of genes selected for quantitative reverse
transcription polymerase chain reaction was presented in this DiB article.
PMID- 28417100
TI - Data for TROTS - The Radiotherapy Optimisation Test Set.
AB - The Radiotherapy Optimisation Test Set (TROTS) is an extensive set of problems
originating from radiotherapy (radiation therapy) treatment planning. This
dataset is created for 2 purposes: (1) to supply a large-scale dense dataset to
measure performance and quality of mathematical solvers, and (2) to supply a
dataset to investigate the multi-criteria optimisation and decision-making nature
of the radiotherapy problem. The dataset contains 120 problems (patients),
divided over 6 different treatment protocols/tumour types. Each problem contains
numerical data, a configuration for the optimisation problem, and data required
to visualise and interpret the results. The data is stored as HDF5 compatible
Matlab files, and includes scripts to work with the dataset.
PMID- 28417101
TI - Role of Active Listening and Listening Effort on Contralateral Suppression of
Transient Evoked Otoacousic Emissions.
AB - BACKGROUND AND OBJECTIVES: The present study aimed to investigate the effect of
active listening and listening effort on the contralateral suppression of
transient evoked otoacoustic emissions (CSTEOAEs). SUBJECTS AND METHODS: Twenty
eight young adults participated in the study. Transient evoked otoacoustic
emissions (TEOAEs) were recorded using 'linear' clicks at 60 dB peSPL, in three
contralateral noise conditions. In condition 1, TEOAEs were obtained in the
presence of white noise in the contralateral ear. While, in condition 2, speech
was embedded into white noise at +3, -3, and -9 dB signal-to-noise ratio (SNR)
and delivered to the contralateral ear. The SNR was varied to investigate the
effect of listening effort on the CSTEOAE. In condition 3, speech was played
backwards and embedded into white noise at -3 dB SNR. The conditions 1 and 3
served as passive listening condition and the condition 2 served as active
listening condition. In active listening condition, the participants categorized
the words in to two groups (e.g., animal and vehicle). RESULTS: CSTEOAE was found
to be largest in the presence of white noise, and the amount of CSTEOAE was not
significantly different between active and passive listening conditions
(condition 2 and 3). Listening effort had an effect on the CSTEOAE, the amount of
suppression increased with listening effort, when SNR was decreased from +3 dB to
-3 dB. However, when the SNR was further reduced to -9 dB, there was no further
increase in the amount of CSTEOAE, instead there was a reduction in the amount of
suppression. CONCLUSIONS: The findings of the present study show that listening
effort might affect CSTEOAE.
PMID- 28417102
TI - Prognostic Factors for Recovery from Sudden Sensorineural Hearing Loss: A
Retrospective Study.
AB - BACKGROUND AND OBJECTIVES: This study aimed to investigate prognostic factors in
patients with idiopathic sudden sensorineural hearing loss (ISSNHL). SUBJECTS AND
METHODS: From January 2007 to December 2011, a retrospective chart review
identified 494 consecutive patients with ISSNHL. Demographic, audiometric, and
clinical data were analyzed using a logistic regression test. RESULTS: Hearing
recovery from ISSNHL was significantly associated with factors such as age,
duration from onset of symptoms to commencement of treatment, severity of the
initial pure tone threshold, and the treatment method. Intratympanic (IT) steroid
administration alone showed a comparable efficiency to oral steroid
administration with or without IT steroid injection. In patients who received IT
steroid injection, the duration from onset to treatment, severity of initial
hearing loss, and sequential IT steroid injection following systemic steroid
administration were statistically associated with hearing improvement.
CONCLUSIONS: Age, severity of initial pure tone threshold, duration from onset to
treatment, initial speech discrimination, and initial pure tone threshold are
statistically significant prognostic factors related to hearing improvement in
ISSNHL. IT steroid injection as an initial single treatment is comparable to
systemic oral steroid administration.
PMID- 28417103
TI - Effect of Age and Severity of Facial Palsy on Taste Thresholds in Bell's Palsy
Patients.
AB - BACKGROUND AND OBJECTIVES: To investigate whether taste thresholds, as determined
by electrogustometry (EGM) and chemical taste tests, differ by age and the
severity of facial palsy in patients with Bell's palsy. SUBJECTS AND METHODS:
This study included 29 patients diagnosed with Bell's palsy between January 2014
and May 2015 in our hospital. Patients were assorted into age groups and by
severity of facial palsy, as determined by House-Brackmann Scale, and their taste
thresholds were assessed by EGM and chemical taste tests. RESULTS: EGM showed
that taste thresholds at four locations on the tongue and one location on the
central soft palate, 1 cm from the palatine uvula, were significantly higher in
Bell's palsy patients than in controls (p<0.05). In contrast, chemical taste
tests showed no significant differences in taste thresholds between the two
groups (p>0.05). The severity of facial palsy did not affect taste thresholds, as
determined by both EGM and chemical taste tests (p>0.05). The overall mean
electrical taste thresholds on EGM were higher in younger Bell's palsy patients
than in healthy subjects, with the difference at the back-right area of the
tongue differing significantly (p<0.05). In older individuals, however, no
significant differences in taste thresholds were observed between Bell's palsy
patients and healthy subjects (p>0.05). CONCLUSIONS: Electrical taste thresholds
were higher in Bell's palsy patients than in controls. These differences were
observed in younger, but not in older, individuals.
PMID- 28417104
TI - Combined Bifrontal Transcranial Direct Current Stimulation and Tailor-Made
Notched Music Training in Chronic Tinnitus.
AB - BACKGROUND AND OBJECTIVES: We evaluated the short-term treatment outcomes of
combined bifrontal transcranial direct current stimulation (tDCS) and tailor-made
notched music training (TMNMT) in tinnitus patients. The associations of patient
characteristics with treatment responsiveness were investigated. SUBJECTS AND
METHODS: Four sessions of bifrontal tDCS (F4: anode, F3: cathode) and TMNMT were
conducted over a 2-week period in tinnitus patients. For tDCS, the stimulation
intensity was 1.5 mA and the duration was approximately 20 min. During tDCS,
patients listened to music lacking the frequency band within 1 octave of the
tinnitus frequency. Patients were also instructed to listen to this music at home
for at least 2 hours per day. One month after the final tDCS session, loudness
(LD), awareness (AW), annoyance (AN), and effect on life (EL) of tinnitus were
assessed subjectively using a visual analog scale. RESULTS: A total of 14
patients were enrolled in this study. After treatment, a 50% or greater
improvement in AN, AW, EL, and LD was observed in 57.1, 42.9, 35.7, and 28.6% of
patients, respectively. Furthermore, 78.6% of patients showed a 50% or greater
improvement in their tinnitus handicap inventory scores. For AN, the absence of
sleep disturbance was significantly associated with treatment responsiveness
(p=0.041, OR=24.0). CONCLUSIONS: Combined bifrontal tDCS and TMNMT is a promising
treatment for chronic tinnitus. To maximize the treatment outcomes of this
therapy, sleep disturbances should also be addressed in candidate patients.
PMID- 28417105
TI - Substitution Patterns of Phoneme Errors in Hearing Aid and Cochlear Implant
Users.
AB - BACKGROUND AND OBJECTIVES: It is acknowledged that speech perceptual errors are
increased in listeners who have sensorineural hearing loss as noise increases.
However, there is a lack of detailed information for their error pattern. The
purpose of the present study was to analyze substitution patterns of phoneme
errors in Korean hearing aid (HA) and cochlear implant (CI) users who are
postlingually deafened adults. SUBJECTS AND METHODS: In quiet and under two noise
conditions, the phoneme errors of twenty HA and fourteen CI users were measured
by using monosyllabic words, and a substitution pattern was analyzed in terms of
manner of articulation. RESULTS: The results showed that both groups had a high
percentage of nasal and plosive substitutions regardless of background
conditions. CONCLUSIONS: This finding will provide vital information for
understanding the speech perception of hearing-impaired listeners and for
improving their ability to communicate when applied to auditory training.
PMID- 28417106
TI - Comparative Analysis of the Combined Therapeutic Effects of Lipoprostaglandin E1
on Sudden Idiopathic Sensorineural Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: Viral and vascular disorders are considered to be a
major cause of idiopathic sudden sensorineural hearing loss (ISSNHL).
Lipoprostaglandin E1 (lipo-PGE1) has vasodilating activity and has been used to
treat ISSNHL. The purpose of this study was to determine the specific therapeutic
effects of lipo-PGE1 and compare them to other treatment modalities for ISSNHL.
SUBJECTS AND METHODS: The study group had 1,052 patients diagnosed with ISSNHL.
All were treated with steroid, carbogen inhalation, stellate ganglion block
(SGB), or PGE1. The CP group (steroid, carbogen inhalation, and PGE1 injection;
288 patients) was treated with lipo-PGE1 and carbogen inhalation, the CS group
(steroid, carbogen inhalation, and stellate ganglion block; 232 patients) with
steroid, carbogen inhalation, and SGB, the C group (steroid and carbogen
inhalation; 284 patients) with steroid and carbogen, and the control group
(steroid only; 248 patients) with steroid only. Patients in the groups receiving
lipo-PGE1 received a continuous infusion of 10 uL lipo-PGE1. RESULTS: The overall
recovery rate after treatment was 52.2%, and recovery rates by group were 67.7%
in the CP group, 54.3% in the CS group, 52.1% in the C group, and 32.2% in the
control group. Therefore, the therapeutic results in groups treated with lipo
PGE1 were better than results in other groups. The difference was statistically
significant. CONCLUSIONS: The study results suggested that the CP group received
effective treatment modalities for ISSNHL. The combined therapy of lipo-PGE1 with
carbogen inhalation in patients with ISSNHL was more beneficial than other
treatment modalities.
PMID- 28417107
TI - Analysis of Effect of Eggshell Membrane Patching for Moderate-to-Large Traumatic
Tympanic Membrane Perforation.
AB - BACKGROUND AND OBJECTIVES: To evaluate the effect of eggshell membrane (ESM)
patching for tympanic membrane (TM) perforation, and to investigate correlations
between healing time and age, gender, patching time, perforation size, and
perforation location. SUBJECTS AND METHODS: One hundred and seventy-five patients
diagnosed with traumatic TM perforation at the Department of Otorhinolaryngology
Head and Neck Surgery, Korea University Ansan Hospital, between January 2008 and
October 2013. Patients were divided into two groups, according to perforation
edge approximation or ESM patching treatment. Healing time was compared between
the group that received perforation edge approximation and the group that
received ESM patching. Perforation grade, age, onset, and location were also
compared between the two groups. RESULTS: ESM patching significantly improved
healing time compared to spontaneous healing, especially in patients with
moderate or large traumatic TM perforations (>=grade II). However, patient age,
gender, perforation location, and especially timing of procedure, did not
significantly affect healing time. CONCLUSIONS: ESM patching can be a good
treatment choice to promote tympanic membrane healing in large traumatic TM
perforations.
PMID- 28417108
TI - Factors Prognostic of Season-Associated Sudden Sensorineural Hearing Loss: A
Retrospective Observational Study.
AB - BACKGROUND AND OBJECTIVES: This study examined whether the prognosis of sudden
deafness was dependent on the time of onset and evaluated the factors affecting
prognosis during each period. SUBJECTS AND METHODS: Patients who developed sudden
hearing loss from January 2005 to December 2015 were evaluated retrospectively.
Meteorological data were obtained from the official website of the Korea
Meteorological Administration. Factors prognostic of hearing recovery rate were
analyzed. RESULTS: The hearing recovery rate of the 318 patients who developed
sudden deafness did not differ significantly by month. Mean temperature and daily
temperature range at onset of sudden deafness were not associated with recovery
rate. CONCLUSIONS: The recovery rate in patients with sudden deafness did not
differ markedly by season.
PMID- 28417109
TI - Intractable Methicillin-Resistant Staphylococcus Aureus Otorrhea with Silicone
Impression in the Middle Ear.
AB - We report a case of methicillin-resistant Staphylococcus aureus (MRSA) otorrhea
with impression material of hearing aid in the middle ear. The patient had
chronic otitis media in the right ear with sensorineural hearing loss in both
ears. The silicone flowed into the middle ear through a tympanic membrane
perforation during the process of making an ear mold. Several days after hearing
aid fitting, the patient had severe otalgia, intractable otorrhea, aggravated
hearing loss, and dizziness. The pus culture and sensitivity test revealed MRSA.
After topical treatment using diluted vinegar irrigation and ototopical
vancomycin solution, intractable otorrhea was controlled. The infected silicone
impression was removed by canal wall-up mastoidectomy, and hearing was saved. We
present here a review of the literature regarding silicone impression in the
middle ear after hearing aid mold fitting.
PMID- 28417110
TI - Kawasaki Disease and Labyrinthitis: An Underdiagnosed Complication.
AB - Sensorineural hearing loss (SNHL) that is seldom cited as a Kawasaki disease (KD)
complication is known as an additional, potentially severe, and frequently
irreversible sequel. Furthermore the vestibular functions of KD have been
underestimated and it could be an important complication combined with SNHL in
KD. We described a case that a 4 year-old boy who developed vestibular loss with
SNHL has recovered successfully with a combined treatment.
PMID- 28417111
TI - Speech Intelligibility in Persian Hearing Impaired Children with Cochlear
Implants and Hearing Aids.
AB - The aim of present study is to evaluate and compare speech intelligibility in
hearing impaired children with cochlear implants (CI) and hearing aid (HA) users
and children with normal hearing (NH). The sample consisted of 45 Persian
speaking children aged 3 to 5-years-old. They were divided into three groups, and
each group had 15, children, children with CI and children using hearing aids in
Hamadan. Participants was evaluated by the test of speech intelligibility level.
Results of ANOVA on speech intelligibility test showed that NH children had
significantly better reading performance than hearing impaired children with CI
and HA. Post-hoc analysis, using Scheffe test, indicated that the mean score of
speech intelligibility of normal children was higher than the HA and CI groups;
but the difference was not significant between mean of speech intelligibility in
children with hearing loss that use cochlear implant and those using HA. It is
clear that even with remarkabkle advances in HA technology, many hearing impaired
children continue to find speech production a challenging problem. Given that
speech intelligibility is a key element in proper communication and social
interaction, consequently, educational and rehabilitation programs are essential
to improve speech intelligibility of children with hearing loss.
PMID- 28417114
TI - Polymorphs of two dimensional phosphorus and arsenic: insight from an
evolutionary search.
AB - Using an evolutionary algorithm, in conjunction with density functional theory
(DFT) based electronic, ionic and cell relaxation, we perform an extensive search
for the crystal structures of possible two dimensional (2D) allotropes of
phosphorus and arsenic. In addition to previously reported allotropes like alpha,
beta, gamma and delta, we discover four new allotropes, whose cohesive energies
differ from that of the ground state (alpha and beta, in the case of P and As,
respectively) by merely ~2-10 meV per atom. In terms of electrical properties,
all of them are semiconductors, although the magnitude and nature of the bandgap
(direct/indirect) vary considerably. We explain the diversity in terms of the
atomic character of the valence and conduction bands of the allotropes. Barring a
few exceptions, we find that the effective mass of both the electron and hole has
marked anisotropies for most of the allotropes.
PMID- 28417113
TI - Temporal Registration in In-Utero Volumetric MRI Time Series.
AB - We present a robust method to correct for motion and deformations in in-utero
volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires
robust alignment across time in the presence of substantial and unpredictable
motion. We make a Markov assumption on the nature of deformations to take
advantage of the temporal structure in the image data. Forward message passing in
the corresponding hidden Markov model (HMM) yields an estimation algorithm that
only has to account for relatively small motion between consecutive frames. We
demonstrate the utility of the temporal model by showing that its use improves
the accuracy of the segmentation propagation through temporal registration. Our
results suggest that the proposed model captures accurately the temporal dynamics
of deformations in in-utero MRI time series.
PMID- 28417112
TI - Lectin-type oxidized LDL receptor-1 distinguishes population of human
polymorphonuclear myeloid-derived suppressor cells in cancer patients.
AB - Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important
regulators of immune responses in cancer and have been directly implicated in
promotion of tumor progression. However, the heterogeneity of these cells and
lack of distinct markers hampers the progress in understanding of the biology and
clinical importance of these cells. Using partial enrichment of PMN-MDSC with
gradient centrifugation we determined that low density PMN-MDSC and high density
neutrophils from the same cancer patients had a distinct gene profile. Most
prominent changes were observed in the expression of genes associated with
endoplasmic reticulum (ER) stress. Surprisingly, low-density lipoprotein (LDL)
was one of the most increased regulators and its receptor oxidized LDL receptor 1
OLR1 was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized
LDL receptor 1 (LOX-1) encoded by OLR1 was practically undetectable in
neutrophils in peripheral blood of healthy donors, whereas 5-15% of total
neutrophils in cancer patients and 15-50% of neutrophils in tumor tissues were
LOX-1+. In contrast to their LOX-1- counterparts, LOX-1+ neutrophils had gene
signature, potent immune suppressive activity, up-regulation of ER stress, and
other biochemical characteristics of PMN-MDSC. Moreover, induction of ER stress
in neutrophils from healthy donors up-regulated LOX-1 expression and converted
these cells to suppressive PMN-MDSC. Thus, we identified a specific marker of
human PMN-MDSC associated with ER stress and lipid metabolism, which provides new
insight to the biology and potential therapeutic targeting of these cells.
PMID- 28417115
TI - Synthesis of calcium carbonate in trace water environments.
AB - Calcium carbonate (CaCO3) was synthesized from diverse water-free alcohol
solutions, resulting in the formation of vaterite and calcite precipitates, or
stable particle suspensions, with the dimensions and morphologies depending upon
the conditions used. The obtained results shed light on the importance of
solvation during crystallization of CaCO3 and open a novel synthetic route for
its precipitation in organic solvents.
PMID- 28417116
TI - A long persistence phosphor tailored quasi-solid-state dye-sensitized solar cell
that generates electricity in sunny and dark weathers.
AB - An all-weather quasi-solid-state dye-sensitized solar cell is built using a long
persistence phosphor tailored mesoscopic TiO2 photoanode and a three-dimensional
conducting polymer gel electrolyte. The so-called all-weather solar cell yields a
maximum efficiency of 28.7% in the dark, making a promising photovoltaic
revolutionary for state-of-the-art photovoltaics.
PMID- 28417117
TI - Poly(naphthalene diimide) vinylene: solid state red emission and semiconducting
properties for transistors.
AB - In this work, a conjugated polymer PNV is developed, linking naphthalene diimide
with a vinyl linkage. Owing to the C-HO hydrogen bond between the carbonyl and
the vinyl, PNV exhibits a high red emission with a quantum yield of 33.4% in the
solid state while it shows n-type properties with an electron mobility up to 1.5
* 10-3 cm2 V-1 s-1 in organic field effect transistors, simultaneously.
PMID- 28417118
TI - A very simple method for the preparation of Au/TiO2 plasmonic photocatalysts
working under irradiation of visible light in the range of 600-700 nm.
AB - By using a facile calcination method, we succeeded in the preparation of
partially spherical gold particles supported on TiO2 exhibiting photoabsorption
due to surface plasmon resonance at around 620 nm. Surprisingly, the selective
oxidation of benzyl alcohol to benzaldehyde occurred in an aqueous suspension of
thus-prepared Au/TiO2 under irradiation of light from a Xe lamp with an R60 cut
off filter (lambda > 600 nm), and the apparent quantum efficiency reached 7.2% at
625 nm and 4.2% even at 700 nm.
PMID- 28417119
TI - Dehydrogenative cross-coupling of o-carborane with thiophenes via Ir-catalyzed
regioselective cage B-H and C(sp2)-H activation.
AB - Ir-Catalyzed -COOH directed site-selective B-H/C-H dehydrogenative cross-coupling
of o-carborane with thiophenes has been achieved for the first time. Without any
pre-functionalization, carboranyl carboxylic acids and thiophenes can serve as
suitable coupling partners, resulting in the preparation of 4-thienyl-o
carboranes in a simple one-pot process for potential applications in materials.
PMID- 28417120
TI - Enhanced CO2 uptake by intramolecular proton transfer reactions in amino
functionalized pyridine-based ILs.
AB - This work presents a new strategy for the promotion of CO2 uptake by an
intramolecular proton transfer reaction in amino functionalized hydroxypyridine
based anions.
PMID- 28417122
TI - Frequency-control of protein translocation across an oscillating nanopore.
AB - The translocation of a lipid binding protein (LBP) is studied using a
phenomenological coarse-grained computational model that simplifies both chain
and pore geometry. We investigated via molecular dynamics the interplay between
transport and unfolding in the presence of a nanopore whose section oscillates
periodically in time with a frequency omega, a motion often referred to as the
radial breathing mode (RBM). We found that the LPB when mechanically pulled into
the vibrating nanopore exhibits a translocation dynamics that in some frequency
range is accelerated and shows a frequency locking to the pore dynamics. The main
effect of pore vibrations is the suppression of stalling events of the
translocation dynamics, hence, proper frequency tuning allows both regularization
and control of the overall transport process. Finally, the interpretation of the
simulation results is easily achieved by resorting to a first passage theory of
elementary driven-diffusion processes.
PMID- 28417123
TI - Design of anion-selective PET probes based on azacryptands: the effect of pH on
binding and fluorescence properties.
AB - Design of PET probes for anions working in an aqueous buffered solution is
described. The design has been used to develop selective fluorescent probes for
sulfate and pyrophosphate. The relationship between the selectivity of receptors
towards anions, their conformation, fluorescence response and the pH of the
solution has been studied in detail.
PMID- 28417124
TI - Revisiting the (E + A) ? (e + a) problems of polyatomic systems with trigonal
symmetry: general expansions of their vibronic Hamiltonians.
AB - In this work, we derive general expansions in vibrational coordinates for the (E
+ A) ? (e + a) vibronic Hamiltonians of molecules with one and only one C3 axis.
We first derive the expansion for the lowest C3 symmetry. Additional symmetry
elements systematically eliminate terms in the expansion. We compare our
expansions with the previous results for two cases, the and the C3 (E + A) ? e.
The first comparison demonstrates the robustness, completeness, conciseness, and
convenience of our formalism. There is a systematic discrepancy in the second
comparison. We discuss the origin of the discrepancy and use a numerical example
to corroborate our expansion. Our formalism covers 153 vibronic problems in 6
point groups. It also gives general expansions for the spin-orbit vibronic
Hamiltonians of the p-type (E + A) ? (e + a) problems.
PMID- 28417127
TI - On the formation of stripe, sigma, and honeycomb phases in a core-corona system.
AB - Using Monte Carlo simulations and free-energy calculations, we investigate the
phase behaviour of a two-dimensional core-corona system. We model this system as
particles consisting of an impenetrable hard core of diameter sigmaHD surrounded
by a purely repulsive soft corona of diameter delta = 1.95sigmaHD. At low
densities, we observe the spontaneous formation of a phase with a stripe texture
as well as a honeycomb-like phase driven by both energy and entropy
considerations. At high densities, we find that a two-dimensional analogue of the
periodic sigma phase, considered as an approximant of dodecagonal quasicrystals,
is energetically stabilised with respect to two distinct dodecagonal
quasicrystals, namely, a square-triangle tiling and a square-triangle-shield
tiling. We also find the formation of stable hexagonal phases at three distinct
density ranges, which are energetically driven, i.e. by minimising the overlap of
coronas. Furthermore, our calculations show that the low-density dodecagonal
quasicrystal that was previously reported by Dotera et al., [Nature, 2014, 506,
208] is kinetically formed in the coexistence region between the honeycomb and
the medium-density hexagonal phase.
PMID- 28417128
TI - Surface reactivity and vacancy defects in single-layer borophene polymorphs.
AB - Single-layer borophene is a novel 2D material which combines high strength, light
weight and metallicity. Using first-principles calculations, we systematically
investigate the defect formation and surface reactivity in three major borophene
polymorphs (alpha, beta and triangular). We find that beta-B is generally the
most reactive borophene form, while alpha-B is the least reactive. In particular,
there is more than 1.5 eV difference in substitutional energies for typical
dopants in beta-B and alpha-B polymorphs. Single vacancy defects can be created
quite easily in all borophene sheets with formation energies (0.16 to 1.93 eV)
much lower than those in graphene (7.69 eV). Adatom adsorption is exothermic and
stabilizes electron-deficient boron monolayers. Many interesting properties arise
from the rich structural chemistry of borophene, comprising four-, five-, and six
coordinated atoms, as well as hexagonal vacancies.
PMID- 28417130
TI - Iron isotopic composition of blood serum in anemia of chronic kidney disease.
AB - Chronic kidney disease (CKD) is a general term for disorders that affect the
structure and function of the kidneys. Iron deficiency (ID) and anemia occur in
the vast majority of CKD patients, most of whom are elderly. However,
establishing the cause of anemia in CKD, and therefore making an informed
decision concerning the corresponding therapeutic treatment, is still a
challenge. High-precision Fe isotopic analysis of blood serum samples of CKD
patients with and without ID/anemia was performed via multi-collector inductively
coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with
CKD and/or iron disorders showed a heavier serum Fe isotopic composition than
controls. Many clinical parameters used for the diagnosis and follow-up of anemia
correlated significantly with the serum Fe isotopic composition. In contrast, no
relation was observed between the serum Fe isotopic composition and the estimated
glomerular filtration rate as a measure of kidney function. Among the CKD
patients, the serum Fe isotopic composition was substantially heavier in the
occurrence of ID anemia, while erythropoietin-related anemia did not exert this
effect. The Fe isotopic composition can thus be useful for distinguishing these
different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin
related anemia.
PMID- 28417131
TI - Asthma in Singapore: Past, Present and Future.
PMID- 28417132
TI - Awareness and Attitudes of Community-Dwelling Individuals in Singapore towards
Participating in Advance Care Planning.
AB - INTRODUCTION: Advance care planning (ACP) is an important aspect of end-of-life
care that has been shown to improve patient autonomy in decision-making and
reduce stress for surviving family members. Given the rapidly ageing population
in Singapore, a greater emphasis on end-of-life care planning is needed. This
study therefore sought to examine the awareness and attitudes of the general
Singaporean community towards participating in ACP, which are not known hitherto.
MATERIALS AND METHODS: A 24-item interviewer-administered questionnaire was
constructed and administered via door-to-door survey amongst community-dwelling
residents living in Housing and Development Board (HDB) flats across Singapore,
selected via a two-stage stratified random sampling. RESULTS: Of the 406
completed surveys, 14.4% of respondents had heard of ACP (n = 58), mostly through
the media (67.9%), from family and friends (21.4%) and healthcare providers
(21.4%). Only 26.8% of those who had previously heard of ACP knew how to begin an
ACP discussion and 12.5% of them had a prior ACP discussion. After education, the
majority of respondents were willing to begin an ACP discussion (n = 236, 60.1%).
Being of an older age, having a life threatening illness, and having more
knowledge about ACP were significant factors associated with willingness to have
an ACP discussion. Barriers included perceiving oneself as still healthy and
preferring the family to make decisions instead. CONCLUSION: There is a low
awareness but high expressed willingness to engage in an ACP discussion amongst
the Singaporean community. More efforts are needed to educate the public about
ACP, engage the family unit and correct the present misconceptions.
PMID- 28417133
TI - Comorbid Diabetes and Depression among Older Adults - Prevalence, Correlates,
Disability and Healthcare Utilisation.
AB - INTRODUCTION: The objectives of this current study were to: 1) examine the
prevalence and correlates of diabetes mellitus (DM) among older adults (aged 60
years and above) in a multi-ethnic population; 2) examine the prevalence and
correlates of comorbid DM and depression among them; and 3) assess the effect of
comorbid depression on disability, cognition and healthcare utilisation.
MATERIALS AND METHODS: Data for the current study came from the Well-being of the
Singapore Elderly (WiSE) study; a single phase, cross-sectional survey conducted
among Singapore residents aged 60 years and above. A total of 2565 respondents
completed the survey; depression was assessed using the Automated Geriatric
Examination for Computer Assisted Taxonomy (AGECAT) while a diagnosis of DM was
considered if respondents stated that a doctor had diagnosed them with DM.
RESULTS: DM was reported by 25.5% of the population. The prevalence of depression
was significantly higher in those diagnosed with DM than those without DM (6% vs
3%). After adjusting for sociodemographic correlates, smoking and other chronic
conditions, DM remained significantly associated with depression and subsyndromal
depression. However, after including measures of functioning and cognitive
impairment as covariates, DM was not significantly related to depression and
subsyndromal depression. Those with comorbid DM and depression were more likely
to be of Indian and Malay ethnicity, aged 75 to 84 years (versus 60 to 74 years)
and widowed. CONCLUSION: Given the significant association of certain
sociodemographic groups with comorbid depression among those with DM, targeted
interventions for prevention and early diagnosis in these groups should be
considered.
PMID- 28417134
TI - Predictors and Moderators of Post-traumatic Stress Disorder: An Investigation of
Anxiety Sensitivity and Resilience in Individuals with Chronic Pain.
AB - INTRODUCTION: Anxiety sensitivity has been proposed as a psychological
vulnerability factor for post-traumatic stress disorder (PTSD). Studies have also
supported the protective role of resilience for overcoming the negative effects
of trauma exposure. Given the linkages between anxiety sensitivity, resilience,
trauma exposure and post-traumatic stress, this study explored the potential
moderating roles of anxiety sensitivity and resilience on the association between
trauma history and PTSD symptoms in a sample of individuals with chronic pain.
MATERIALS AND METHODS: A total of 100 patients with chronic pain were recruited
from a large public hospital. Patients who had pain lasting for more than 3
months and a pain intensity rating of at least 4/10 were included. The study
participants were administered measures of PTSD symptoms (PTSD Checklist -
Civilian Version), resilience (Brief Resilient Coping Scale) and anxiety
sensitivity (Anxiety Sensitivity Index). RESULTS: An analysis of outcome measures
indicated that anxiety sensitivity and resilience were independently associated
with PTSD symptoms, where betas were 0.57 and -0.23, respectively. The
relationship between trauma and PTSD symptom severity was also moderated by
anxiety sensitivity. Trauma history was associated with higher PTSD symptom
severity only in those with high anxiety sensitivity. However, contrary to the
hypotheses, resilience did not serve as a moderator. CONCLUSION: There are
potential benefits of PTSD interventions that increase resilience and decrease
anxiety sensitivity in individuals with chronic pain, especially for those who
have experienced a traumatic event. Given that the presence of PTSD
symptomatology in chronic pain populations negatively impact patient well-being,
it would be important for clinicians to assess, monitor and treat PTSD in
individuals with chronic pain.
PMID- 28417135
TI - A Training Model for Introducing a Novel Surgical Procedure into Clinical
Practice: Our Experience on Peroral Endoscopic Myotomy for Achalasia.
PMID- 28417136
TI - Too Old for Surgery? Outcomes of Hip Fracture Surgery in Centenarians.
PMID- 28417137
TI - Adult Onset Sporadic Cerebellar Ataxia in Singapore: Diagnostic Outcomes of
Paraneoplastic Antibody Testing and Early Clinical Features of Paraneoplastic
Cerebellar Degeneration.
PMID- 28417139
TI - The Fragility Index: a P-value in sheep's clothing?
PMID- 28417138
TI - Long-term exposure to ambient air pollution and traffic noise and incident
hypertension in seven cohorts of the European study of cohorts for air pollution
effects (ESCAPE).
AB - Aims: We investigated whether traffic-related air pollution and noise are
associated with incident hypertension in European cohorts. Methods and results:
We included seven cohorts of the European study of cohorts for air pollution
effects (ESCAPE). We modelled concentrations of particulate matter with
aerodynamic diameter <=2.5 um (PM2.5), <=10 um (PM10), >2.5, and <=10 um
(PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of
participants with land use regression. Residential exposure to traffic noise was
modelled at the facade according to the EU Directive 2002/49/EC. We assessed
hypertension as (i) self-reported and (ii) measured (systolic BP >= 140 mmHg or
diastolic BP >= 90 mmHg or intake of BP lowering medication (BPLM). We used
Poisson regression with robust variance estimation to analyse associations of
traffic-related exposures with incidence of hypertension, controlling for
relevant confounders, and combined the results from individual studies with
random-effects meta-analysis. Among 41 072 participants free of self-reported
hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years
of follow-up. Incidence of self-reported hypertension was positively associated
with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI):1.08; 1.37] per
5 ug/m3) and PM2.5 absorbance (RR 1.13 [95% CI:1.02; 1.24] per 10 - 5m - 1).
These estimates decreased slightly upon adjustment for road traffic noise. Road
traffic noise was weakly positively associated with the incidence of self
reported hypertension. Among 10 896 participants at risk, 3549 new cases of
measured hypertension occurred. We found no clear associations with measured
hypertension. Conclusion: Long-term residential exposures to air pollution and
noise are associated with increased incidence of self-reported hypertension.
PMID- 28417140
TI - Onychomycosis Due to Arthrinium arundinis: A Case Report.
PMID- 28417141
TI - Incidence and Prevalence of Psoriasis in Denmark.
AB - The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012
were examined. There was a female predominance ranging between 50.0% (2007) and
55.4% (2009), and the mean age at time of diagnosis was 47.7-58.7 years. A total
of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence
rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak
incidence of 199.5 in 2010. Incidence rates were higher for women, and patients
aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e.
methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA)
increased over the study course, and were used in 15.0% of all patients. Biologic
agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were
utilized in 2.7% of patients. On a national level, incidence of psoriasis
fluctuated during the 10-year study course. The relationship between psoriasis
incidence and age appeared to be relatively linear, and disease prevalence was
comparable to that in other European countries.
PMID- 28417142
TI - Heterozygous PDGFRB Mutation in a Three-generation Family with Autosomal Dominant
Infantile Myofibromatosis.
PMID- 28417143
TI - Impact of High Age and Comorbidity on Management Decisions and Adherence to
Guidelines in Patients with Keratinocyte Skin Cancer.
AB - Appropriate medical decision-making in patients with keratinocyte skin cancer
(KSC) can be challenging, especially in those with a limited life expectancy
(LEx). Treatment should be beneficial for the individual patient, the risk of
both over- and under-treatment should be carefully considered, and deviation from
guideline recommendations may be necessary. In this study retrospective analysis
was performed to determine the influence of age and comorbidity, both factors
strongly related to limited LEx, on KSC management in daily practice. After
analysis of 401 patients it was found that management in patients with KSC is not
influenced, or is only minimally influenced, by high age and comorbidity. Better
integration of aspects related to a limited LEx in KSC management might optimize
care and prevent overtreatment. Future research on the general prognostication,
prediction of the patient burden caused by tumour and treatment, and time-to
benefit in KSC management is strongly recommended.
PMID- 28417144
TI - The effect of reconstruction works on planktonic bacterial diversity of a unique
thermal lake revealed by cultivation, molecular cloning and next generation
sequencing.
AB - The aim of this study was to gain detailed information about the diversity of
planktonic bacterial communities of a worldwide special peat bedded natural
thermal spa lake, and to reveal the effect of a lake wall reconstruction work. To
compare the efficiency of different methods used for analyzing bacterial
diversity, cultivation, molecular cloning and pyrosequencing were applied
simultaneously. Despite the almost unchanged physical-chemical parameters and
cell count values of lake water, remarkable differences were observed in the
planktonic bacterial community structures during and after the reconstruction by
all applied microbiological approaches. Rhodobacter sp. was found to be one of
the most abundant community members during the works probably due to the sediment
stirring effect of the reconstruction. Following the reconstruction higher
diversity was detected than during the works by all approaches. Bacterial strains
related to species Chryseobacterium and Exiguobacterium, furthermore sequences
related to Arcobacter, Gemmobacter and MWH-UniP1 aquatic group were identified in
the highest proportion at that time. Although the differences revealed by
cultivation based and independent community structures were significant, only
minor disparities were found by molecular cloning and next generation sequencing
techniques.
PMID- 28417145
TI - Relationship in Pacemaker Neurons Between the Long-Term Correlations of Membrane
Voltage Fluctuations and the Corresponding Duration of the Inter-Spike Interval.
AB - Several studies of the behavior in the voltage and frequency fluctuations of the
neural electrical activity have been performed. Here, we explored the particular
association between behavior of the voltage fluctuations in the inter-spike
segment (VFIS) and the inter-spike intervals (ISI) of F1 pacemaker neurons from
H. aspersa, by disturbing the intracellular calcium handling with cadmium and
caffeine. The scaling exponent alpha of the VFIS, as provided by detrended
fluctuations analysis, in conjunction with the corresponding duration of ISI to
estimate the determination coefficient R 2 (48-50 intervals per neuron, N = 5)
were all evaluated. The time-varying scaling exponent alpha(t) of VFIS was also
studied (20 segments per neuron, N = 11). The R 2 obtained in control conditions
was 0.683 ([0.647 0.776] lower and upper quartiles), 0.405 [0.381 0.495] by using
cadmium, and 0.151 [0.118 0.222] with caffeine (P < 0.05). A non-uniform scaling
exponent alpha(t) showing a profile throughout the duration of the VFIS was
further identified. A significant reduction of long-term correlations by cadmium
was confirmed in the first part of this profile (P = 0.0001), but no significant
reductions were detected by using caffeine. Our findings endorse that the
behavior of the VFIS appears associated to the activation of different
populations of ionic channels, which establish the neural membrane potential and
are mediated by the intracellular calcium handling. Thus, we provide evidence to
consider that the behavior of the VFIS, as determined by the scaling exponent
alpha, conveys insights into mechanisms regulating the excitability of pacemaker
neurons.
PMID- 28417147
TI - Cortical Histomorphometry of the Human Humerus During Ontogeny.
AB - Modeling and remodeling are two key determinants of human skeletal growth though
little is known about the histomorphometry of cortical bone during ontogeny. In
this study, we examined the density and geometric properties of primary and
secondary osteons (osteon area and diameter, vascular canal area and diameter) in
subperiosteal cortical bone from the human humerus (n = 84) between birth and age
18 years. Sections were removed from the anterior midshaft aspect of humeri from
skeletons. Age-at-death was reconstructed using standard osteological techniques.
Analyses revealed significant correlation between the histomorphometric variables
and age. Higher densities of primary osteons occurred between infancy and 7 years
of age but were almost completely replaced by secondary osteons after 14 years of
age. The geometry of primary osteons was less clearly related to age. Secondary
osteons were visible after 2 years of age and reached their greatest densities in
the oldest individuals. Osteon size was positively but weakly influenced by age.
Our data imply that modeling and remodeling are age-dependent processes that vary
markedly from birth to adulthood in the human humerus.
PMID- 28417146
TI - Repeated mild traumatic brain injury in female rats increases lipid peroxidation
in neurons.
AB - Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by
repeated insult. Animal models of repeated closed-head mTBI provide the
opportunity to define acute pathological mechanisms as the number of mTBI
increases. Furthermore, little is known about the effects of mTBI impact site,
and how this may affect brain function. We use a closed head, weight drop model
of mTBI that allows head movement following impact, in adult female rats to
determine the role of the number and location of mTBI on brain pathology and
behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact
sites were used, anterior (bregma) and posterior (lambda). Location of the impact
had no significant effect on impact forces (450 N), and the weight impact
locations were on average 5.4 mm from the desired impact site. No between
location vertical linear head kinematic differences were observed immediately
following impact, however, in the 300 ms post-impact, significantly higher mean
vertical head displacement and velocity were observed in the mTBI lambda trials.
Breaches of the blood brain barrier were observed with three mTBI over bregma,
associated with immunohistochemical indicators of damage. However, an increased
incidence of hairline fractures of the skull and macroscopic haemorrhaging made
bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over
lambda did not cause skull fractures and were examined more comprehensively, with
outcomes following one, two or three mTBI or sham, delivered at 1 day intervals,
assessed on days 1-4. We observe a mild behavioural phenotype, with subtle
deficits in cognitive function, associated with no identifiable neuroanatomical
or inflammatory changes. However, an increase in lipid peroxidation in a subset
of cortical neurons following two mTBI indicates increasing oxidative damage with
repeated injury in female rats, supported by increased amyloid precursor protein
immunoreactivity with three mTBI. This study of acute events following closed
head mTBI identifies lipid peroxidation in neurons at the same time as cognitive
deficits. Our study adds to existing literature, providing biomechanics data and
demonstrating mild cognitive disturbances associated with diffuse injury,
predominantly to grey matter, acutely following repeated mTBI.
PMID- 28417148
TI - Relationship Between Nutritional Factors and Hip Bone Density in Individuals with
Chronic Stroke.
AB - The aim of this study was to investigate the relationship between dietary habits
and hip bone health in community-dwelling individuals with chronic stroke. The
usual dietary intake of 94 individuals with chronic stroke (30 women, mean age:
59.0 years) was assessed by a 3-day food record within a single week. Dual-energy
X-ray absorptiometry was used to measure bone mineral density (BMD) at both hips.
The results showed that low hip bone mass was found in 59 and 50 of the
participants on the affected and unaffected side, respectively. The mean hip BMD
was also significantly lower on the affected side than the unaffected side (P <
0.001). The intake of total fat, carbohydrates, calcium, magnesium, iron, zinc,
fiber, folic acid, vitamin B1, B2, B3, B6, C, and K was significantly lower than
the respective recommended daily intake values (P < 0.05). Multiple regression
analyses revealed that after adjusting for the effects of age, sex, body mass
index, post-stroke duration, side of paresis, motor impairment, physical activity
level, walking endurance, total calories intake, and total number of medications,
intake of protein, fiber, and magnesium remained significantly associated with
hip T score on the affected side, accounting for 4.2, 4.4, and 3.2% of the
variance, respectively. On the other hand, intake of protein and fiber was
independently associated with hip T score on the unaffected side, explaining 2.7
and 5.2% of the variance, respectively. The results highlighted the potential
relevance of diet modification in maintaining bone health post stroke, which
would require further study.
PMID- 28417149
TI - Clincal interpretation of the anti-tuberculosis drug concentrations in diabetic
and non-diabetic tuberculosis patients.
PMID- 28417150
TI - Torpor patterns in common hamsters with and without access to food stores.
AB - Hibernating species significantly reduce energy expenditure during winter by
entering torpor. Nevertheless, the various benefits of hibernation might be
counteracted by negative effects of torpor such as immune depression, oxidative
stress, or neuronal impairment. Considering these trade-offs, adequate energy
reserves could allow animals to reduce the time spent in torpor or the extent of
metabolic depression. Common hamsters use food stores during hibernation and
previously documented high individual variations in body temperature patterns
during winter could, therefore, be related to differences in external energy
reserves. In this study, we manipulated the availability of food stores under
laboratory conditions to investigate potential effects on hibernation patterns.
Female hamsters were kept in artificial burrows in climate chambers and
subcutaneous temperature was recorded using implanted data loggers. One group had
access to large food stores, whereas another group received daily food portions
which were removed on the next day if not consumed. Almost all hamsters without
access to food stores hibernated, while less than half of the individuals with
food stores entered deep torpor. Individuals without food hoards additionally
expressed more short torpor bouts and exhibited lower minimum subcutaneous
temperatures during torpor than those with food stores. Thus, individuals
confronted with lacking food reserves were more likely to hibernate and
additionally saved energy by entering short torpor bouts more frequently and
remaining at lower subcutaneous temperature both during torpor and euthermic
periods. In conclusion, our results demonstrate that food store availability
affects torpor expression and also highlight variation in torpor patterns and
energy-saving strategies in common hamsters.
PMID- 28417151
TI - A review of the role and clinical utility of anti-Ro52/TRIM21 in systemic
autoimmunity.
AB - Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found
in a number of systemic autoimmune conditions including Sjogren's syndrome,
systemic lupus erythematosus and systemic sclerosis, appearing in about half of
these patients. Once coupled with its closely related antibody, anti-Ro60 as the
anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct
pathogenic disease involvement and distinct clinical properties. As a result,
recent attention has turned to this antibody and its clinical associations and
utility. There is a suggestion of anti-Ro52 being associated with more clinical
and laboratory markers of disease; however, marked disagreements occur about its
association with various clinical entities such as interstitial lung disease and
Raynaud's phenomena. Nevertheless, with a relative paucity of studies about these
across the systemic autoimmunity paradigm, limited confidence can be invested in
these conclusions. Although the antibody holds great potential as a biomarker,
further studies examining its clinical utility are needed. This paper will review
the mechanisms of Ro52 as an autoantigen and the clinical associations of anti
Ro52 in human autoimmunity.
PMID- 28417152
TI - Review of surgical and anesthetic management for esophageal atresia with
tracheoesophageal fistula, unilateral pulmonary agenesis and dextrocardia.
AB - Association of unilateral severe pulmonary atresia or agenesis and esophageal
atresia (EA) with or without tracheoesophageal fistula (TEF) and dextrocardia is
a rare and highly lethal combination. We report a case of a full-term female
infant who had EA with TEF, right lung agenesis, and dextrocardia. Repair of the
fistula took place on day of life 3. We describe anesthetic and surgical concerns
of this patient's case which are keys to a good operative outcome as well as
follow-up for the patient.
PMID- 28417153
TI - Laparoscopic sacrocolpopexy compared with open abdominal sacrocolpopexy for vault
prolapse repair: a randomised controlled trial.
AB - INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the functional outcome
after laparoscopic sacrocolpopexy versus open sacrocolpopexy in women with vault
prolapse. METHODS: A multicentre randomised controlled trial was carried out at
four teaching and two university hospitals in the Netherlands in women with
symptomatic vault prolapse requiring surgical treatment. Participants were
randomised for laparoscopic or open sacrocolpopexy. Primary outcome was disease
specific quality of life measured using the Urinary Distress Inventory (UDI)
questionnaire at 12 months' follow-up. Secondary outcomes included anatomical
outcome and perioperative data. We needed 74 participants to show a difference of
10 points on the prolapse domain of the UDI 12 months after surgery (power of
80%, alpha error 0.05). RESULTS: Between 2007 and 2012, a total of 74 women were
randomised. Follow-up after 12 months showed no significant differences in domain
scores of the UDI between the two groups. After 12 months, both groups reported a
UDI score of 0.0 (IQR: 0-0) for the domain "genital prolapse", which was the
primary outcome. There were no significant differences between the two groups (p
= 0.93). The number of severe complications was 4 in the laparoscopic group
versus 7 in the open abdominal group (RR 0.57; 95% CI 0.50-2.27). There was less
blood loss and a shorter hospital stay after laparoscopy; 2 (IQR 2-3) versus 4
(IQR 3-5) days, which was statistically different. There was no significant
difference in anatomical outcome at 12 months. CONCLUSION: Our trial provides
evidence to support a laparoscopic approach when performing sacrocolpopexy, as
there was less blood loss and hospital stay was shorter, whereas functional and
anatomical outcome were not statistically different.
PMID- 28417154
TI - Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome?
AB - INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI), defined as mixed
symptoms of stress urinary incontinence (SUI) and overactive bladder (OAB), is a
difficult entity if conservative treatment has failed. Cure rates are low
compared with SUI, particularly the OAB component, may deteriorate after sling
insertion. Bulking agents pose an appealing alternative for the treatment of MUI.
They have shown beneficial effect in small case studies, but larger series are
lacking. The aim of this prospective study was an analysis of treatment efficacy
and safety profile of the bulking agent, Bulkamid, in female patients with MUI.
METHODS: One hundred fifty-four women with MUI symptoms (components of SUI/OAB
within the limits of 60-40% either way) received bulking therapy with
polyacrylamide hydrogel (Bulkamid). Patients were followed-up 3 months
postoperatively. Primary outcome was the domain Incontinence impact on the King's
Health Questionnaire (KHQ). Secondary outcomes were the other KHQ domains, visual
analog scale (VAS), and International Continence Society (ICS) standardized pad
weight test as objective measurement of incontinence. RESULTS: Statistically
significant improvements were found for all KHQ domains, pad weight test, and the
visual analog scale (VAS) before and after bulking. Overall complication rate was
13%. CONCLUSIONS: This study has shown improvement in MUI after bulking therapy
according to both subjective and objective outcomes. We can advocate bulking
therapy for treating MUI, as it is simple and safe and shows both objective and
subjective improvement and relief. Long-term results (up to 1 year) are awaited.
PMID- 28417155
TI - Pelvic floor symptoms and quality of life changes during first pregnancy: a
prospective cohort study.
AB - INTRODUCTION AND HYPOTHESIS: We describe pelvic floor function in nulliparous
pregnant women. MATERIALS AND METHODS: Nulliparous midwifery patients completed
the Incontinence Severity Index (ISI), Pelvic Floor Impact Questionnaire (PFIQ
7), Wexner Fecal Incontinence Scale (W), and answered questions about sexual
activity and perineal pain at baseline during the first (T1), second (T2), or
third trimester (T3) and repeated in late T3. They also underwent a Pelvic Organ
Prolapse Quantification (POP-Q) exam at their baseline visit. Data were compared
across trimesters. Analysis of variance (ANOVA) and logistic regression accounted
for repeated measures and was controlled for age and education. RESULTS: We
recruited 627 women. In T1, 124 women gave baseline data and completed
questionnaires; in T2, 403; and in early T3, 96 (496 repeated questionnaires in
later T3). Besides an increase in genital hiatus and perineal body (all adjusted
p < .05), physical exam measures did not differ between trimesters. As pregnancy
progressed, urinary incontinence (UI) (T1 = 33, T2 = 44, T3 = 69% women with ISI
>0, all comparisons p < .02) and Incontinence Impact Questionnaire (IIQ-7) scores
increased. Fecal incontinence (FI) increased (T1 = 8, T2 = 15, T3 = 16% from T2
to T3, p = .04); the Colorectal-Anal Impact Questionnaire (CRAIQ-7) scores did
not. Perineal pain increased (T1 = 17, T2 = 18 and T3 = 40%, all adjusted p <
.001), and sexual activity decreased (T1 = 94, T2 = 90, T3 = 77% sexually active,
T1 vs T3 and T2 vs T3, p < .001) as pregnancy progressed. CONCLUSIONS: During
pregnancy, women experience worsening UI, FI, and perineal pain. UI symptoms are
associated with a negative impact on quality of life (QoL). Sexual activity
decreased and POP-Q stage did not change.
PMID- 28417156
TI - Patient satisfaction after laparoscopic lateral suspension with mesh for pelvic
organ prolapse: outcome report of a continuous series of 417 patients.
AB - INTRODUCTION AND HYPOTHESIS: Sacropexy is considered the gold standard for the
treatment of pelvic organ prolapse (POP) although dissection of the promontory
may be challenging, particularly in obese women. Laparoscopic lateral suspension
with mesh (LLS) could be an alternative. METHODS: LLS provides lateral attachment
by fibrosis of a vesicovaginal mesh. Clinical evaluation was performed at 1 year
using the simplified POP quantification system (POP-Q). Primary outcomes were
objective and subjective cure at 1 year. After a mean of 7.2 years the rates of
reoperation and complications were assessed as secondary outcomes. Patient
satisfaction was evaluated by telephone interview using a ten-point-scale and the
PGI-I scale. Factors predicting satisfaction were determined by logistic
regression analysis. RESULTS: A total of 417 patients were treated between 2003
and 2011. At 1 year 78.4% of patients were asymptomatic and anatomic success
rates were 91.6% for the anterior compartment, 93.6% for the apical compartment
and 85.3% for the posterior compartment. The complication rate of Clavien-Dindo
grade III or higher was 2.2%. The mesh exposure rate was 4.3% and the reoperation
rate was 7.3%. Of the 417 patients, 214 participated in the telephone interview.
Over 85% rated their situation as improved and satisfaction was associated with
the absence of concomitant hysterectomy. CONCLUSIONS: LLS is a safe technique
with promising results in terms of a composite outcome, low complication rates
and high long-term patient satisfaction. However, a randomized controlled trial
is needed to establish the technique as an alternative to sacropexy in the
treatment of POP in obese and high morbidity patients.
PMID- 28417157
TI - Impact of cachexia on outcomes in aggressive lymphomas.
AB - Cancer cachexia is defined as a state of involuntary weight loss, attributed to
altered body composition with muscle mass loss and/or loss of adiposity.
Identifying the association between cancer cachexia and outcomes may pave the way
for novel agents that target the cancer cachexia process. Clinical parameters for
measurement of cancer cachexia are needed. We conducted a single-institution
retrospective analysis that included 86 NHL patients with the aim of identifying
an association between cancer cachexia and outcomes in aggressive lymphomas using
the cachexia index (CXI) suggested by Jafri et al. (Clin Med Insights Oncol 9:87
93, 15). Impact of cachexia factors on progression-free survival (PFS) and
overall survival (OS) were assessed using log-rank test and Cox proportional
hazards regression. Patients were dichotomized around the median CXI into "non
cachectic" (CXI >=49.8, n = 41) and "cachectic" (CXI <49.8, n = 40) groups.
Cachectic patients had significantly worse PFS (HR 2.18, p = 0.044) and OS (HR =
4.05, p = 0.004) than non-cachectic patients. Cachexia as defined by the CXI is
prognostic in aggressive lymphomas and implies that novel therapeutic strategies
directed at reversing cachexia may improve survival in this population.
PMID- 28417158
TI - Incidence and predictive factors of Internet addiction among Chinese secondary
school students in Hong Kong: a longitudinal study.
AB - PURPOSE: Internet use has global influences on all aspects of life and has become
a growing concern. Cross-sectional studies on Internet addiction (IA) have been
reported but causality is often unclear. More longitudinal studies are warranted.
METHODS: We investigated incidence and predictors of IA conversion among
secondary school students. A 12-month longitudinal study was conducted among Hong
Kong Chinese Secondary 1-4 students (N = 8286). Using the 26-item Chen Internet
Addiction Scale (CIAS; cut-off >63), non-IA cases were identified at baseline.
Conversion to IA during the follow-up period was detected, with incidence and
predictors derived using multi-level models. RESULTS: Prevalence of IA was 16.0%
at baseline and incidence of IA was 11.81 per 100 person-years (13.74 for males
and 9.78 for females). Risk background factors were male sex, higher school
forms, and living with only one parent, while protective background factors were
having a mother/father with university education. Adjusted for all background
factors, higher baseline CIAS score (ORa = 1.07), longer hours spent online for
entertainment and social communication (ORa = 1.92 and 1.63 respectively), and
Health Belief Model (HBM) constructs (except perceived severity of IA and
perceived self-efficacy to reduce use) were significant predictors of conversion
to IA (ORa = 1.07-1.45). CONCLUSIONS: Prevalence and incidence of IA conversion
were high and need attention. Interventions should take into account risk
predictors identified, such as those of the HBM, and time management skills
should be enhanced. Screening is warranted to identify those at high risk (e.g.
high CIAS score) and provide them with primary and secondary interventions.
PMID- 28417159
TI - Endangered Mangroves in Segara Anakan, Indonesia: Effective and Failed Problem
Solving Policy Advice.
AB - The success of scientific knowledge transfer depends on if the decision maker can
transform the scientific advice into a policy that can be accepted by all
involved actors. We use a science-policy interactions model called research
integration-utilization to observe the process of scientific knowledge transfer
in the case of endangered mangroves in Segara Anakan, Indonesia. Scientific
knowledge is produced within the scientific system (research), science-based
solutions to problems are practically utilized by political actors (utilization),
and important links between research and utilization must be made (integration).
We looked for empirical evidence to test hypotheses about the research
integration-utilization model based on document analysis and expert interviews.
Our study finds that the failures in knowledge transfer are caused by the
inappropriate use of scientific findings. The district government is expected by
presidential decree to only used scientifically sound recommendations as a
prerequisite for designing the regulation. However, the district government
prefers to implement their own solutions because they believe that they
understand the solutions better than the researcher. In the process of
integration, the researcher cannot be involved, since the selection of scientific
recommendations here fully depends on the interests of the district government as
the powerful ally.
PMID- 28417160
TI - Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin
releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients
with negative or inconclusive [18F]Fluoroethylcholine-PET/CT.
AB - PURPOSE/BACKGROUND: [18F]fluoroethylcholine (18FECH) has been shown to be a
valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited
accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that
binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT
is a promising technique for staging and restaging of PCa. We explore the value
of GRPr-PET using the 68Ga-labeled GRPr antagonist RM2 in a selected population
of patients with biochemically recurrent PCa and a negative/inconclusive 18FECH
PET/CT. MATERIAL AND METHODS: In this retrospective study 16 men with biochemical
PCa relapse and negative (n = 14) or inconclusive (n = 2) 18FECH-PET/CT underwent
whole-body 68Ga-RM2-PET/CT. Mean time from 18FECH-PET/CT to 68Ga-RM2-PET/CT was
6.1 +/- 6.8 months. Primary therapies in these patients were radical
prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients
(87.5%) had already undergone salvage therapies because of biochemical relapse
prior to 68Ga-RM2-PET/CT imaging. Mean +/- SD PSA at 68Ga-RM2-PET/CT was 19.4 +/-
53.5 ng/ml (range 1.06-226.4 ng/ml). RESULTS: 68Ga-RM2-PET/CT showed at least one
region with focal pathological uptake in 10/16 patients (62.5%), being suggestive
of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n
= 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive 68Ga-RM2
scans were positively confirmed by surgical resection and histology of the
lesions (n = 2), by response to site-directed therapies (n = 2) or by further
imaging (n = 3). Patients with a positive 68Ga-RM2-scan showed a significantly
higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative
scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant
antihormonal therapy had no apparent impact on the detection of recurrent
disease. CONCLUSION: Even in this highly selected population of patients with
known biochemical recurrence but negative or inconclusive 18FECH-PET/CT, a 68Ga
RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases.
Thus, 68Ga-RM2-PET/CT deserves further investigation as a promising imaging
modality for imaging PCa recurrence.
PMID- 28417161
TI - IFT54 regulates IFT20 stability but is not essential for tubulin transport during
ciliogenesis.
AB - Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary
components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT
B complex and is also associated with cytoplasmic microtubules (MTs). Loss of
IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal
calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been
proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled
coil (CC) domain binds IFT20. However, the precise function of these domains in
vivo is not well understood. We showed that in Chlamydomonas, loss of IFT54
completely blocks ciliogenesis but does not affect spindle formation and proper
cell cycle progression, even though IFT54 interacts with mitotic MTs.
Interestingly, IFT54 lacking the CH domain allows proper flagellar assembly. The
CH domain is required for the association of IFT54 with the axoneme but not with
mitotic MTs, and also regulates the flagellar import of IFT54 but not IFT81 and
IFT46. The C-terminal CC domain is essential for IFT54 to bind IFT20, and for its
recruitment to the basal body and incorporation into IFT complexes. Complete loss
of IFT54 or the CC domain destabilizes IFT20. ift54 mutant cells expressing the
CC domain alone rescue the stability of IFT20 and form stunted flagella with
accumulation of both IFT-A component IFT43 and IFT-B component IFT46, indicating
that IFT54 also functions in IFT turn-around at the flagellar tip.
PMID- 28417162
TI - S100A6 protein: functional roles.
AB - S100A6 protein belongs to the A group of the S100 protein family of Ca2+-binding
proteins. It is expressed in a limited number of cell types in adult normal
tissues and in several tumor cell types. As an intracellular protein, S100A6 has
been implicated in the regulation of several cellular functions, such as
proliferation, apoptosis, the cytoskeleton dynamics, and the cellular response to
different stress factors. S100A6 can be secreted/released by certain cell types
which points to extracellular effects of the protein. RAGE (receptor for advanced
glycation endproducts) and integrin beta1 transduce some extracellular S100A6's
effects. Dosage of serum S100A6 might aid in diagnosis in oncology.
PMID- 28417163
TI - Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells.
AB - Nicotinamide (NAM), a form of vitamin B3, plays essential roles in cell
physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a
substrate to a class of enzymes that catalyze non-redox reactions. These non
redox enzymes include the sirtuin family proteins which deacetylate target
proteins while cleaving NAD+ to yield NAM. Since the finding that NAM exerts
feedback inhibition to the sirtuin reactions, NAM has been widely used as an
inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role
in certain cell physiology. However, once administered to cells, NAM is rapidly
converted to NAD+ and, therefore, the cellular concentration of NAM decreases
rapidly while that of NAD+ increases. The result would be an inhibition of SIRT1
for a limited duration, followed by an increase in the activity. This possibility
raises a concern on the validity of the interpretation of the results in the
studies that use NAM as a SIRT1 inhibitor. To understand better the effects of
cellular administration of NAM, we reviewed published literature in which
treatment with NAM was used to inhibit SIRT1 and found that the expected
inhibitory effect of NAM was either unreliable or muted in many cases. In
addition, studies demonstrated NAM administration stimulates SIRT1 activity and
improves the functions of cells and organs. To determine if NAM administration
can generate conditions in cells and tissues that are stimulatory to SIRT1, the
changes in the cellular levels of NAM and NAD+ reported in the literature were
examined and the factors that are involved in the availability of NAD+ to SIRT1
were evaluated. We conclude that NAM treatment can hypothetically be stimulatory
to SIRT1.
PMID- 28417165
TI - Comparative study of outcomes after ankle arthrodesis shows higher complication
rates in cases operated upon by general orthopaedic surgeons.
AB - INTRODUCTION: A functional assessment of 38 patients after ankle arthrodesis for
the evaluation of the necessity of surgeons-specialisation was carried out by
means of clinical evaluation and gait analysis after an average follow up of 30
months. METHODS: Scores were used to grade ankle function. Gate analysis was
examined to determine the effect of arthrodesis on the ankle in relation to the
surgeons' experience. Under conditions of normal daily living, we found
significant differences in life quality between patients operated upon by experts
in orthopaedic foot and ankle surgery (group A) and patients operated by general
orthopaedic surgeons (group B). RESULTS: All patients in group A had orthograde
stance. Wrong screw positioning and a failed neutral tibio-talar position were
the main problems in group B. Due to this, the re-operation rate was 10%.
CONCLUSION: Our findings may have implications for surgical training programs and
for regionalisation of complex surgical procedures.
PMID- 28417164
TI - Individual differences in voluntary alcohol intake in rats: relationship with
impulsivity, decision making and Pavlovian conditioned approach.
AB - RATIONALE: Alcohol use disorder (AUD) has been associated with suboptimal
decision making, exaggerated impulsivity, and aberrant responses to reward-paired
cues, but the relationship between AUD and these behaviors is incompletely
understood. OBJECTIVES: This study aims to assess decision making, impulsivity,
and Pavlovian-conditioned approach in rats that voluntarily consume low (LD) or
high (HD) amounts of alcohol. METHODS: LD and HD were tested in the rat gambling
task (rGT) or the delayed reward task (DRT). Next, the effect of alcohol (0-1.0
g/kg) was tested in these tasks. Pavlovian-conditioned approach (PCA) was
assessed both prior to and after intermittent alcohol access (IAA). Principal
component analyses were performed to identify relationships between the most
important behavioral parameters. RESULTS: HD showed more optimal decision making
in the rGT. In the DRT, HD transiently showed reduced impulsive choice. In both
LD and HD, alcohol treatment increased optimal decision making in the rGT and
increased impulsive choice in the DRT. PCA prior to and after IAA was comparable
for LD and HD. When PCA was tested after IAA only, HD showed a more sign-tracking
behavior. The principal component analyses indicated dimensional relationships
between alcohol intake, impulsivity, and sign-tracking behavior in the PCA task
after IAA. CONCLUSIONS: HD showed a more efficient performance in the rGT and
DRT. Moreover, alcohol consumption enhanced approach behavior to reward
predictive cues, but sign-tracking did not predict the level of alcohol
consumption. Taken together, these findings suggest that high levels of voluntary
alcohol intake are associated with enhanced cue- and reward-driven behavior.
PMID- 28417166
TI - Vaccine impact in homogeneous and age-structured models.
AB - A general model of an imperfect vaccine for a childhood disease is presented and
the effects of different types of vaccine failure on transmission were
investigated using models that consider both homogeneous and age-specific mixing.
The models are extensions of the standard SEIR equations with an additional
vaccinated component that allows for five different vaccine parameters: three
types of vaccine failure in decreasing susceptibility to infection via failure in
degree ("leakiness"), take ("all-or-nothingness") and duration (waning of vaccine
derived immunity); one parameter reflecting the relative reduction in
infectiousness of vaccinated individuals who get infected; and one parameter that
reflects the relative reduction in reporting probability of vaccinated
individuals due to a possible reduction in severity of symptoms. Only the first
four parameters affect disease transmission (as measured by the basic
reproduction number). The reduction in transmission due to vaccination is
different for age-structured models than for homogeneous models. Notably, if the
vaccine exhibits waning protection this could be larger for an age-structured
model with high contact rates between young children who are still protected by
the vaccine and lower contact rates between adults for whom protection might have
already waned. Analytic expressions for age-specific "vaccine impacts" were also
derived. The overall vaccine impact is bounded between the age-specific impact
for the oldest age class and that of the youngest age class.
PMID- 28417168
TI - RDX degradation in bioaugmented model aquifer columns under aerobic and low
oxygen conditions.
AB - Degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in laboratory
columns following biostimulation and bioaugmentation was investigated using
sediment and groundwater from a contaminated aquifer at a US Navy facility. No
RDX degradation was observed following aerobic biostimulation with either
fructose or lactate (both 0.1 mM) prior to bioaugmentation. Replicate columns
were then bioaugmented with either Gordonia sp. KTR9, Pseudomonas fluorescens I-C
(Ps I-C), or both strains. Under aerobic conditions (influent dissolved oxygen
(DO) >6 mg/L), RDX was degraded following the addition of fructose, and to a
lesser extent with lactate, in columns bioaugmented with KTR9. No degradation was
observed in columns bioaugmented with only Ps I-C under aerobic conditions,
consistent with the known anaerobic RDX degradation pathway for this strain. When
influent DO was reduced to <2 mg/L, good RDX degradation was observed in the KTR9
bioaugmented column, and some degradation was also observed in the Ps I-C
bioaugmented column. After DO levels were kept below 1 mg/L for more than a
month, columns bioaugmented with KTR9 became unresponsive to fructose addition,
while RDX degradation was still observed in the Ps I-C-bioaugmented columns.
These results indicate that bioaugmentation with the aerobic RDX degrader KTR9
could be effective at sites where site geology or geochemistry allow higher DO
levels to be maintained. Further, inclusion of strains capable of anoxic RDX
degradation such as Ps I-C may facilitate bimodal RDX removal when DO levels
decrease.
PMID- 28417167
TI - Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a
useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in
preoperative chemoradiotherapy for patients with rectal cancer.
AB - PURPOSE: Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based
chemotherapy is the standard of care for rectal cancer. The effect of additional
chemotherapy during the period between the completion of radiotherapy and surgery
remains unclear. Predictive factors for CRT may differ between combination
chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). METHODS: The
subjects were 54 patients with locally advanced rectal cancer who received
preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed
according to the tumor regression grade (TRG). The expression levels of 18 CRT
related genes were determined using RT-PCR assay. RESULTS: A pathological
response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate
logistic regression analysis for pathological response, the overall expression
levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the
accuracy rate of the predictive model was 83.3%. The effects of the gene
expression levels of GGH on the response differed significantly according to the
treatment regimen. The total pathological response rate of both high-GGH patients
in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. CONCLUSION:
Additional treatment with 5-FU-based chemotherapy during the interval between
radiotherapy and surgery is not beneficial in patients who have received 5-FU
based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in
tumor tissues can predict the response to preoperative CRT including either S-1
or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may
be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.
PMID- 28417169
TI - Rational design of substrate binding pockets in polyphosphate kinase for use in
cost-effective ATP-dependent cascade reactions.
AB - Adenosine-5'-triphosphate (ATP) is the energy equivalent of the living system.
Polyphosphate (polyP) is the ancient energy storage equivalent of organisms.
Polyphosphate kinases (PPKs) catalyze the polyP formation or ATP formation, to
store energy or to regenerate ATP, respectively. However, most PPKs are active
only in the presence of long polyPs, which are more difficult and more expensive
to generate than the short polyPs. We investigated the PPK preference towards
polyPs by site-directed mutagenesis and computational simulation, to understand
the mechanism and further design enzymes for effective ATP regeneration using
short polyPs for in vitro cascade reactions, which are highly desired for
research and applications. The results suggest that the short polyPs inhibit PPK
by blocking the ADP-binding pocket. Structural comparison between PPK
(Corynebacterium glutamicum) and PPK (Sinorhizobium meliloti) indicates that
three amino acid residues, i.e., lysine, glutamate, and threonine, are involved
in the activity towards short polyP by fixing the adenosine group of ADP in
between the subunits of the dimer, while the terminal phosphate group of ADP
still offers an active site, which presents a binding pocket for ADP. A proposed
triple mutant PPK (SMc02148-KET) demonstrates significant activity towards short
polyP to form ATP from ADP. The obtained high glutathione titer (38.79 mM) and
glucose-6-phosphate titer (87.35 mM) in cascade reactions with ATP regeneration
using the triple mutant PPK (SMc02148-KET) reveal that the tailored PPK
establishes the effective ATP regeneration system for ATP-dependent reactions.
PMID- 28417170
TI - Reduced dose CT with model-based iterative reconstruction compared to standard
dose CT of the chest, abdomen, and pelvis in oncology patients: intra-individual
comparison study on image quality and lesion conspicuity.
AB - PURPOSE: To compare image quality and lesion conspicuity of reduced dose (RD) CT
with model-based iterative reconstruction (MBIR) compared to standard dose (SD)
CT in patients undergoing oncological follow-up imaging. METHODS: Forty-four
cancer patients who had a staging SD CT within 12 months were prospectively
included to undergo a weight-based RD CT with MBIR. Radiation dose was recorded
and tissue attenuation and image noise of four tissue types were measured.
Reproducibility of target lesion size measurements of up to 5 target lesions per
patient were analyzed. Subjective image quality was evaluated for three readers
independently utilizing 4- or 5-point Likert scales. RESULTS: Median radiation
dose reduction was 46% using RD CT (P < 0.01). Median image noise across all
measured tissue types was lower (P < 0.01) in RD CT. Subjective image quality for
RD CT was higher (P < 0.01) in regard to image noise and overall image quality;
however, there was no statistically significant difference regarding image
sharpness (P = 0.59). There were subjectively more artifacts on RD CT (P < 0.01).
Lesion conspicuity was subjectively better in RD CT (P < 0.01). Repeated target
lesion size measurements were highly reproducible both on SD CT (ICC = 0.987) and
RD CT (ICC = 0.97). CONCLUSIONS: RD CT imaging with MBIR provides diagnostic
imaging quality and comparable lesion conspicuity on follow-up exams while
allowing dose reduction by a median of 46% compared to SD CT imaging.
PMID- 28417171
TI - Resolution-optimized headspace gas chromatography-ion mobility spectrometry (HS
GC-IMS) for non-targeted olive oil profiling.
AB - A prototype gas chromatography-ion mobility spectrometry (GC-IMS) system,
hyphenating temperature-ramped headspace GC to a modified drift time IMS cell,
was evaluated and compared to a conventional, isothermal capillary column (CC)
IMS system on the example of the geographical differentiation of extra virgin
olive oils (EVOO) from Spain and Italy. It allows orthogonal, 2D separation of
complex samples and individual detection of compounds in robust and compact
benchtop systems. The information from the high-resolution 3D fingerprints of
volatile organic compound (VOC) fractions of EVOO samples were extracted by
specifically developed chemometric MATLAB(r) routines to differentiate between
the different olive oil provenances. A combination of unsupervised principal
component analysis (PCA) with two supervised procedures, linear discriminant
analysis (LDA) and k-nearest neighbors (kNN), was applied to the experimental
data. The results showed very good discrimination between oils of different
geographical origins, featuring 98 and 92% overall correct classification rate
for PCA-LDA and kNN classifier, respectively. Furthermore, the results showed
that the higher resolved 3D fingerprints obtained from the GC-IMS system provide
superior resolving power for non-targeted profiling of VOC fractions from highly
complex samples such as olive oil. Graphical abstract Principle of the
determination of geographic origins of olive oils by chemometric analysis of
three-dimensional HS-GC-IMS fingerprints.
PMID- 28417172
TI - Simultaneous determination of multiclass pesticide residues in human plasma using
a mini QuEChERS method.
AB - Blood is one of the most assessable matrices for the determination of pesticide
residue exposure in humans. Effective sample preparation/cleanup of biological
samples is very important in the development of a sensitive, reproducible, and
robust method. In the present study, a simple, cost-effective, and rapid gas
chromatography-tandem mass spectrometry method has been developed and validated
for simultaneous analysis of 31 multiclass (organophosphates, organochlorines,
and synthetic pyrethroids) pesticide residues in human plasma by means of a mini
QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. We have
adopted a modified version of the QuEChERS method, which is primarily used for
pesticide residue analysis in food commodities. The QuEChERS method was optimized
by use of different extraction solvents and different amounts and combinations of
salts and sorbents (primary-secondary amines and C18) for the dispersive solid
phase extraction step. The results show that a combination of ethyl acetate with
2% acetic acid, magnesium sulfate (0.4 g), and solid-phase extraction for sample
cleanup with primary-secondary amines (50 mg) per 1-mL volume of plasma is the
most suitable for generating acceptable results with high recoveries for all
multiclass pesticides from human plasma. The mean recovery ranged from 74% to
109% for all the analytes. The limit of quantification and limit of detection of
the method ranged from 0.12 to 13.53 ng mL-1 and from 0.04 to 4.10 ng mL-1
respectively. The intraday precision and the interday precision of the method
were 6% or less and 11% or less respectively. This method would be useful for the
analysis of a wide range of pesticides of interest in a small volume of clinical
and/or forensic samples to support biomonitoring and toxicological applications.
Graphical Abstract Pesticide residues analysis in human plasma using mini
QuEChERS method.
PMID- 28417173
TI - Semiautomated TaqMan PCR screening of GMO labelled samples for (unauthorised)
GMOs.
AB - In most countries, systems are in place to analyse food products for the
potential presence of genetically modified organisms (GMOs), to enforce labelling
requirements and to screen for the potential presence of unauthorised GMOs. With
the growing number of GMOs on the world market, a larger diversity of methods is
required for informative analyses. In this paper, the specificity of an extended
screening set consisting of 32 screening methods to identify different crop
species (endogenous genes) and GMO elements was verified against 59 different GMO
reference materials. In addition, a cost- and time-efficient strategy for DNA
isolation, screening and identification is presented. A module for semiautomated
analysis of the screening results and planning of subsequent event-specific tests
for identification has been developed. The Excel-based module contains
information on the experimentally verified specificity of the element methods and
of the EU authorisation status of the GMO events. If a detected GMO element
cannot be explained by any of the events as identified in the same sample, this
may indicate the presence of an unknown unauthorised GMO that may not yet have
been assessed for its safety for humans, animals or the environment.
PMID- 28417174
TI - Multidimensional single-cell analysis based on fluorescence microscopy and
automated image analysis.
AB - A single-cell analytical technology was developed for evaluating fast-growing
cultures of green algae. The main part of the single-cell analysis is an
epifluorescence microscopy-based cytometric approach combined with an automated
image analysis algorithm and a single-threshold discrimination procedure. The
reliability of the technique in terms of object recognition, evaluating particle
size, and determining chlorophyll was successfully proven via reference analyses.
The microscopy technique was used to determine the size of single cells, the
amount of chlorophyll, and the density of chlorophyll in a model algal culture
(Acutodesmus o.). The algal cells showed unexpected heterogeneity in all single
cell parameters, and exhibited a high correlation between cell size and amount of
chlorophyll but a very low correlation between cell size and chlorophyll density.
For a given cell size, the cell-to-cell heterogeneity of the relative chlorophyll
density showed a spread of 0.02-0.08. This points to large variations in the
architecture and the physiological state of the photosynthetic apparatus in the
cells. This complex situation should be considered in future systems biology
approaches focusing on the relationships between biomass accumulation,
photosynthetic activity, and central carbon metabolism. Graphical abstract
Analysis of cell-to-cell heterogeneity obtained from microscopic images.
PMID- 28417175
TI - Microwave-assisted deglycosylation for rapid and sensitive analysis of N-glycans
via glycosylamine derivatization.
AB - A rapid and sensitive N-glycan profiling strategy for MALDI-MS incorporating the
use of deglycosylation with microwave assistance and the co-derivatization of
glycosylamine labeling with tris(2,4,6-trimethoxyphenyl)phosphonium acetic acid N
hydroxysuccinimide ester (TMPP-Ac-OSu) and methylamidation has been developed in
this work. Notably, highly efficient release and tagging of N-glycans from
ribonuclease B was achieved in less than 90 min, providing up to 35-fold
enhancement of MALDI-MS sensitivity with comparison to underivatized N-glycans.
After further validation with other two standard glycoproteins (ovalbumin and
bovine fetuin), the proposed strategy was applied to human serum for preliminary
pathological analysis of N-glycans between healthy and lung cancer individuals.
As a result, significant differences (T test p value <0.01) of 6 glycan
structures were determined from 54 detected N-glycan structures with only 50 nL
of loading amount and further confirmed through PCA and ROC (AUC) analyses
between two sample sets. Subsequently, the trend of each lung cancer stage and
controls in expression of the selected glycans was implemented with T test and
box-plots. Accordingly, these structures can be used as potential lung cancer
glycan-based biomarkers and for further definition of cancer progression
highlighting the ability of proposed method to rapidly and efficiently analyze N
glycome present in human serum. Graphical abstract MALDI-TOF MS analysis of N
glycans by microwave-assisted deglycosylation and glycosylamine derivatization.
PMID- 28417177
TI - In-situ hydrothermal synthesis of titanium dioxide nanorods on titanium wire for
solid-phase microextraction of polycyclic aromatic hydrocarbons.
AB - Titanium dioxide nanorods were prepared on the surface of titanium wire by
hydrothermal synthesis for use as a solid-phase microextraction (SPME) fiber. The
morphology of the SPME coating was observed by scanning electron microscopy
(SEM). Employed in conjunction with gas chromatography (GC), the fiber was
investigated with five polycyclic aromatic hydrocarbons (PAHs) and three
terphenyls in direct-immersion extraction mode. Various parameters were
optimized, such as the extraction time, the stirring rate, the extraction
temperature, the ionic strength of the sample solution, and the desorption time.
Under the optimized conditions, the SPME-GC analytical method achieved a low
detection limit (0.003 MUg L-1) and wide linear ranges (0.01-100 MUg L-1 and 0.01
200 MUg L-1) along with good correlation coefficients (0.9892-0.9962). The
established method was also used to analyze rainwater and an aqueous solution of
coal ash. The results indicated that this fiber could be applied in real-world
environmental monitoring. The proposed fiber also exhibited excellent durability.
Graphical Abstract The schematic diagram of experimental process.
PMID- 28417176
TI - Functional gold nanoparticles for optical affinity biosensing.
AB - Functional gold nanoparticles (AuNPs) are commonly used to enhance the response
of optical affinity biosensors. In this work, we investigated the effect of
preparation conditions on functional properties of AuNPs functionalized with
antibody (Ab-AuNPs), specifically AuNPs with antibody against carcinoembryonic
antigen (CEA) covalently attached via carboxy-terminated oligo-ethylene thiolate
linker layer. The following parameters of preparation of Ab-AuNP have been found
to have a significant effect on Ab-AuNP performance in affinity biosensors: the
time of reaction of activated AuNPs with antibody, concentrations of antibody and
amino-coupling reagents, and composition of immobilization buffer (molarity and
salt content). In contrast, pH of immobilization buffer has been demonstrated to
have only a minor influence. Our experiments showed that the Ab-AuNPs prepared
under optimum conditions offered a binding efficiency of Ab-AuNPs to CEA as high
as 63%, which is more than 4 times better than the best efficiencies reported for
similar functional AuNPs so far. We employed these Ab-AuNPs with a surface
plasmon resonance (SPR) biosensor for the detection of CEA and showed that the Ab
AuNPs enhanced the sensor response to CEA by a factor of 1000. We also
demonstrated that the Ab-AuNPs allow the biosensor to detect CEA at
concentrations as low as 12 and 40 pg/mL in buffer and 50% blood plasma,
respectively.
PMID- 28417178
TI - Highly sensitive and selective determination of hydrogen sulfide by resonance
light scattering technique based on silver nanoparticles.
AB - We have developed a green approach to prepare DNA-templated silver nanoparticles
(Ag-NPs) from the direct reaction between Ag+ and ascorbic acid in the presence
of DNA and sodium hydroxide. The Ag-NPs showed strong resonance light scattering
(RLS) intensity property. Then, the interaction between hydrogen sulfide (H2S)
and Ag-NPs was studied by measuring their RLS spectra. The results showed that
there is a strong interaction between Ag-NPs and H2S, which resulted in a
decrease in the size of Ag-NPs and a decrease in the RLS intensity of the Ag-NPs
solution at the wavelength of 467 nm. The results demonstrated that the RLS
technique offers a sensitive and simple tool for investigating the interaction
between Ag-NPs and H2S, which can be applied to detect H2S with high sensitivity
and selectivity without complex readout equipment. The linear range for H2S
determination was found to be the range from 5.0 * 10-9 to 1.0 * 10-7 mol L-1,
and the detection limit (3sigma/k) was 2.8 * 10-9 mol L-1. Moreover, the proposed
method was applied for the determination of H2S in natural water samples with
satisfactory results. Graphical abstract The application of Ag-NPs in H2S
detection.
PMID- 28417179
TI - Analysis of honeybush tea (Cyclopia spp.) volatiles by comprehensive two
dimensional gas chromatography using a single-stage thermal modulator.
AB - The applicability of comprehensive two-dimensional gas chromatography (GC*GC)
using a single-stage thermal modulator was explored for the analysis of honeybush
tea (Cyclopia spp.) volatile compounds. Headspace solid phase micro-extraction
(HS-SPME) was used in combination with GC*GC separation on a non-polar * polar
column set with flame ionisation (FID) detection for the analysis of fermented
Cyclopia maculata, Cyclopia subternata and Cyclopia genistoides tea infusions of
a single harvest season. Method optimisation entailed evaluation of the effects
of several experimental parameters on the performance of the modulator, the
choice of columns in both dimensions, as well as the HS-SPME extraction fibre.
Eighty-four volatile compounds were identified by co-injection of reference
standards. Principal component analysis (PCA) showed clear differentiation
between the species based on their volatile profiles. Due to the highly
reproducible separations obtained using the single-stage thermal modulator,
multivariate data analysis was simplified. The results demonstrate both the
complexity of honeybush volatile profiles and the potential of GC*GC separation
in combination with suitable data analysis techniques for the investigation of
the relationship between sensory properties and volatile composition of these
products. The developed method therefore offers a fast and inexpensive
methodology for the profiling of honeybush tea volatiles. Graphical abstract
Surface plot obtained for the GC*GC-FID analysis of honeybush tea volatiles.
PMID- 28417180
TI - Multiplexed assay for protein quantitation in the invertebrate Gammarus fossarum
by liquid chromatography coupled to tandem mass spectrometry.
AB - A highly multiplexed liquid chromatography mass spectrometry-selected reaction
monitoring (SRM)-based assay for determination of 40 potential protein biomarkers
from Gammarus fossarum, an ecotoxicological relevant species, was described. The
assay relies on 71 stable isotope-labeled reported peptide standards for the
quantitation of proteins of interest in relation to essential physiological
functions such as reproductive cycle, defense mechanism, and enzymes involved in
homeostasis process and in energy. A direct linear relationship between the
spiked peptide concentration and the area under the peak was clearly demonstrated
in biological extracts. Precision and accuracy were determined to be between 1.1
and 21% and between 79 and 120%, respectively, depending on the selected protein
in a few samples after optimization of digestion conditions. The validity of the
assay was documented for several biomarkers linked with reproduction and the
molting process was performed with the assessment of protein levels throughout
contrasted physiological process (sex, reproductive status). This assay is easy
to use, robust, sensitive, and has high-throughput capabilities. The proposed
strategy may be extended to any non-model organisms relevant in environmental
science. Graphical abstract ?.
PMID- 28417181
TI - Colonic inflammation in pediatric inflammatory bowel disease: detection with
magnetic resonance enterography.
AB - BACKGROUND: Colonic involvement in pediatric inflammatory bowel disease is
common. Magnetic resonance (MR) enterography is considered the best imaging
modality for pediatric inflammatory bowel disease evaluation. It is unclear
whether the lack of a dedicated large bowel preparation prevents a reliable
colonic assessment. OBJECTIVE: To determine the diagnostic performance of
standard MR enterography in detecting and grading colonic inflammatory activity.
MATERIALS AND METHODS: We retrospectively evaluated children who underwent both
MR enterography and ileocolonoscopy with biopsies <4 weeks apart. Two
radiologists independently reviewed MR examinations and quantified inflammation
in each of the five colonic segments using a standardized MR score system.
Findings were compared with histological examination of the corresponding
segment. Mann-Whitney, Kruskal-Wallis, Jonckheere-Terpstra and Bland-Altman
statistics were used. RESULTS: One hundred seventy-five segments from 37
examinations were included. MR enterography diagnostic performance for
inflammation was as follows: sensitivity 94% (95% confidence interval [CI]: 90
97%), specificity: 64% (95% CI: 57-71%). A significant positive correlation was
found between MR score and inflammatory activity histologically graded (P<0.001,
Jonckheere-Terpstra test). The interobserver agreement was good (mean difference
between MR enterography scores was -0.03; limits of agreement -2.8 to 2.7).
CONCLUSION: Standard MR enterography is sensitive for the detection of actively
inflamed colonic segments. MR enterography might provide useful information for
guiding biopsies and its role as an alternative to ileocolonoscopy in monitoring
colonic disease activity in children should be further investigated.
PMID- 28417183
TI - Patella height is not altered by descending medial open-wedge high tibial
osteotomy (HTO) compared to ascending HTO.
AB - PURPOSE: The primary purpose of the study was to gain insight into geometric
changes of the patellar height (PH) and posterior tibial slope (PTS) after a
biplanar ascending medial open-wedge high tibial osteotomy (HTO) compared to
biplanar descending medial open-wedge HTO in patients with genu varum. METHODS:
Sixty-four patients (mean age 45.2 +/- 8.7 years, females n = 24, males n = 40)
with varus malalignment and medial gonarthrosis were retrospectively studied.
Patients received either a biplanar ascending or descending medial open-wedge
HTO. Radiographic analysis included the assessment of standing total leg axis,
PH, and PTS prior to and after surgery. RESULTS: In the ascending HTO group, PH
decreased significantly by 4.0% (p = 0.037, Caton-Deschamps index) after an
average leg axis valgus-producing correction of 7.1 degrees +/- 2.8 degrees . In
the descending HTO group, with an average leg axis correction of 7.0 degrees +/-
3.7 degrees , there were no significant PH changes. There were no significant
differences between the ascending and descending HTO groups regarding PTS or leg
axis. The mean post-operative leg axis between ascending (1.6 degrees +/- 1.9
degrees ) and descending HTO (1.9 degrees +/- 2.4 degrees ) was not
significantly different. CONCLUSION: Compared to the biplanar ascending medial
open-wedge HTO, the descending HTO did not influence patella height or increase
the posterior tibial slope. In order to respect patellofemoral and slope-related
knee kinematics, a biplanar descending medial open-wedge HTO has proven useful to
control patella height and posterior tibial slope. These findings underscore the
importance of the preoperative patella height assessment in the osteotomy
planning and subsequent choice of the biplanar osteotomy direction. LEVEL OF
EVIDENCE: IV.
PMID- 28417185
TI - Combined Preoperative Portal and Hepatic Vein Embolization (Biembolization) to
Improve Liver Regeneration Before Major Liver Resection: A Preliminary Report.
AB - BACKGROUND: Insufficient volume of the future liver remnant (FLR) is a major
cause of non-resectable disease in patients presenting with primary or metastatic
liver tumours. The objective of this study was to evaluate the safety and
efficacy of the combined preoperative portal and hepatic vein embolization
(biembolization) before extended right liver resections. METHODS: This
retrospective study was performed in a tertiary centre between 2014 and 2015.
Combined right portal and hepatic vein embolization (biembolization) was
proposed, as an alternative to ALPPS procedure, for all patients with primary or
metastatic liver tumour, before right extended hepatectomy. CT scan liver
volumetry was assessed before biembolization, three weeks after biembolization
and one week after surgery. RESULTS: Seven patients underwent biembolization. All
patients had right portal vein embolization (PVE) combined with right hepatic
vein embolization (HVE, n = 4), median HVE (n = 2) and right + median HVE (n =
1). Three patients had preoperative liver disease and two received preoperative
chemotherapy. No biembolization procedure-related complications occurred. The
mean FLR regeneration rate was 52.6% (range: 18.2-187.9) after the
biembolization. One patient with gallbladder carcinoma was not operated because
of peritoneal carcinomatosis diagnosed after the biembolization. The remnant six
patients did not develop postoperative liver failure. CONCLUSIONS: Biembolization
seems to induce safe, reproducible and effective FLR growth before extended right
hepatectomy, in patients with primary or metastatic liver tumour.
PMID- 28417184
TI - Comparison of Epidemiology of the Injuries and Outcomes in Two First-Level Trauma
Centers in Colombia Using the Pan-American Trauma Registry System.
AB - INTRODUCTION: The aim of this study was to compare the epidemiology of traumatic
injuries and mortality outcomes between two tertiary-care trauma centers in
Colombia using data from Pan-American Trauma Registry (PATR). METHODS: January 1
December 31, 2012, data from the Hospital Universitario del Valle (HUV, public)
and Fundacion Valle del Lili (FVL, private) in Cali, Colombia, were considered.
Differences in demographic and clinical information were compared using
descriptive statistics. Propensity score matching was used to match patients on
age, gender, and ISS. Within matched cohorts, multivariable logistic regression
models were used to assess for differences in in-hospital mortality, further
adjusting for insurance type, employment, heart rate, presence of hypotension
(SBP < 90), and GCS score. RESULTS: HUV (8539; 78% male) and FVL (10,456; 60%
male) had a combined total of 18,995 trauma cases in 2012 with comparable mean
ages of 29.7 years. There were significant differences in insurance status,
injury severity, and mechanism of injury between patients at HUV and FLV. On risk
adjusted logistic regression analyses with propensity score matched cohorts, the
odds of death in HUV was higher compared to patients presenting at FVL hospital
(OR [95% CI]:4.93 [3.37-7.21], p < 0.001). CONCLUSION: The study established the
utility of the PATR and revealed important trends in patient demographics, injury
epidemiology, and mortality outcomes, which can be used to target trauma
initiatives throughout the region. It underscores the profound importance that
differences in case mix play in the risk of trauma-related mortality, further
emphasizing the need to monitor and evaluate unique aspects of trauma in LMIC.
LEVEL OF EVIDENCE: III.
PMID- 28417186
TI - Endoscopic Central Lymph Node Dissection via Breast Combined with Oral Approach
for Papillary Thyroid Carcinoma: A Preliminary Study.
AB - OBJECTIVE: To investigate the feasibility and necessity of endoscopic
thyroidectomy with central lymph node dissection via the combined breast and
trans-oral approaches. METHODS: Six patients with papillary thyroid carcinoma who
underwent endoscopic total thyroidectomy with central node dissection via
combined breast and trans-oral approaches from November 2014 to January 2015 in
Zhongshan Hospital, Xiamen University, were analyzed. RESULTS: After completion
of endoscopic central lymph node dissection via the traditional breast approach,
eight pieces of lymph nodes could still be dissected via the trans-oral approach.
Two of these eight pieces were positive for thyroid cancer metastasis.
CONCLUSIONS: It is advisable to perform endoscopic central lymph node dissection
for thyroid carcinoma via the breast approach combined with the trans-oral
approach.
PMID- 28417188
TI - Comparative Transcriptome Sequence Analysis of Sporulation-Related Genes of
Aspergillus cristatus in Response to Low and High Osmolarity.
AB - Aspergillus cristatus undergoes sexual and asexual development under conditions
of low and high osmotic pressure, respectively. In this study, the expression
levels of 107 genes associated with sexual and asexual development were analysed
under conditions of low and high osmotic pressure by RNA sequencing. The results
showed that 37 genes were up-regulated and other genes were down-regulated under
conditions of high osmotic pressure, with most of the up-regulated genes
associated with asexual development and most down-regulated genes associated with
sexual development. These results suggest that osmotic pressure regulated sexual
and asexual development of A. cristatus by controlling the expression levels of
key genes. Meanwhile, there were differences in the expression levels of key
genes associated with the regulation of sexual and asexual development between A.
cristatus and Aspergillus nidulans. Moreover, we verified the reliability of the
results by quantitative real-time polymerase chain reaction analysis of some key
genes. In this study, the relationship between sporulation-related genes and
osmotic pressure at the transcriptome level were analysed, which indicated that
A. cristatus was a useful model organism for the study of osmotic pressure
regulation on sexual and asexual development.
PMID- 28417189
TI - Draft Genome Sequence of a Biosurfactant-Producing Bacillus subtilis UMX-103
Isolated from Hydrocarbon-Contaminated Soil in Terengganu, Malaysia.
AB - The draft genome here presents the sequence of Bacillus subtilis UMX-103. The
bacterial strain was isolated from hydrocarbon-contaminated soil from Terengganu,
Malaysia. The whole genome of the bacterium was sequenced using Illumina HiSeq
2000 sequencing platform. The genome was assembled using de novo approach. The
genome size of UMX-103 is 4,234,627 bp with 4399 genes comprising 4301 protein
coding genes and 98 RNA genes. The analysis of assembled genes revealed the
presence of 25 genes involved in biosurfactant production, where 14 of the genes
are related to biosynthesis and 11 of the genes are in the regulation of
biosurfactant productions. This draft genome will provide insights into the
genetic bases of its biosurfactant-producing capabilities.
PMID- 28417187
TI - Isolation of Viable but Non-culturable Bacteria from Printing and Dyeing
Wastewater Bioreactor Based on Resuscitation Promoting Factor.
AB - Printing and dyeing wastewater with high content of organic matters, high
colority, and poor biochemical performance is hard to be degraded. In this study,
we isolated viable but non-culturable (VBNC) bacteria from printing and dyeing
wastewater with the culture media contained resuscitation promoting factor (Rpf)
protein secreted by Micrococcus luteus, counted the culturable cells number with
the most probable number, sequenced 16S rRNA genes, and performed polymerase
chain reaction-denaturing gradient gel electrophoresis. It is obviously that the
addition of Rpf in the enrichment culture could promote growth and resuscitation
of bacteria in VBNC state to obtain more fastidious bacteria significantly. The
identified bacteria were assigned to nine genera in the treatment group, while
the two strains of Ochrobactrum anthropi and Microbacterium sp. could not be
isolated from the control group. The function of isolated strains was explored
and these strains could degrade the dye of Congo red. This study provides a new
sight into the further study including the present state, composition, formation
mechanism, and recovery mechanism about VBNC bacteria in printing and dyeing
wastewater, which would promote to understand bacterial community in printing and
dyeing wastewater, and to obtain VBNC bacteria from ecological environment.
PMID- 28417190
TI - Larkinella harenae sp. nov., Isolated from Korean Beach Soil.
AB - A Gram-negative, short rod-shaped, gliding motile, and pale pink-pigmented
bacterial strain, designated 15J9-9T, was isolated from the soil of Iho Tewoo
Beach, Jeju Island, Korea, and characterized taxonomically using a polyphasic
approach. Comparative 16S rRNA gene sequence analysis showed that strain 15J9-9T
belonged to the family Cytophagaceae and was related to Larkinella bovis M2T2B15T
(96.5% similarity), Larkinella arboricola Z0532T (95.3% similarity), and
Larkinella insperata LMG 22510T (95.2% similarity). The DNA G+C content of strain
15J9-9T was 48 mol%. The detection of phosphatidylethanolamine,
phosphatidylserine, two unknown aminophospholipids (APL1 and APL2), and two
unknown polar lipids (L1 and L2) in polar lipid profile, menaquinone-7 as the
predominant quinone, and a fatty acid profile of C16:1 omega5c, iso-C15:0, and
iso-C17:0 3-OH as the major fatty acids supported the affiliation of strain 15J9
9T to the genus Larkinella. Based on its phenotypic properties and phylogenetic
distinctiveness, strain 15J9-9T should be classified in the genus Larkinella as a
representative of a novel species, for which the name Larkinella harenae sp. nov.
is proposed. The type strain is 15J9-9T (=KCTC 42999T = JCM 31656T).
PMID- 28417191
TI - Mapping of estradiol binding sites through receptor micro-autoradiography in the
endometrial stroma of early pregnant mice.
AB - Estradiol triggers key biological responses in the endometrium, which rely on the
presence and levels of its cognate receptors on target cells. Employing the
receptor micro-autoradiography (RMAR) technique, we aimed to provide a temporal
and spatial map of the functional binding sites for estradiol in the mouse
endometrial stroma during early pregnancy. Uterine samples from days 1.5 to 7.5
of pregnancy were collected 1 h after tritiated- (3H-) estradiol administration
and prepared for RMAR analysis. Autoradiographic incorporation of 3H-thymidine
(after 1-h pulse) was evaluated over the same gestational interval. Combined RMAR
with either histochemistry with Dolichus biflorus (DBA) lectin or
immunohistochemistry for detection of the desmin further characterized 3H
estradiol binding pattern in uterine Natural Killer (uNK) and decidual cells,
respectively. 3H-estradiol binding levels oscillated in the pregnant endometrial
stroma between the mesometrial and antimesometrial regions as well as the
superficial and deep domains. Although most of the endometrial stromal cells
retained the hormone, a sub-population of them, as well as endothelial and uNK
cells, were unable to do so. Rises in the levels of 3H-estradiol binding preceded
endometrial stromal cell proliferation. 3H-estradiol binding and 3H-thymidine
incorporation progressively decreased along the development of the
antimesometrial decidua. Endothelial proliferation occurred regardless of 3H
estradiol binding, whereas pericytes proliferation was associated with high
levels of hormone binding. Endometrial cell populations autonomously control
their levels of 3H-estradiol binding and retention, a process associated with
their proliferative competence. Collectively, our results illustrate the
intricate regulatory dynamic of nuclear estrogen receptors in the pregnant mouse
endometrium.
PMID- 28417192
TI - Can we predict benign multiple sclerosis? Results of a 20-year long-term follow
up study.
AB - Benign multiple sclerosis (MS) is a discussed clinical entity, with variable
reported prevalence (6-64%) requiring at least 5-10 years of clinical
observation. Moreover, many benign patients progress with time becoming no longer
benign (NLB). The objective of this study is to compare benign MS patients (EDSS
<=3, 10 years from disease onset) who still fulfilled the definition at 20 years
to those NLB. In our retrospective study based on Ottawa Hospital MS Clinic
database, 175 benign patients fulfilled the inclusion criteria (clinically
definite MS, EDSS <=3 at 10 years, disease onset from 1983 to 1993, and clinical
assessments performed at 10 +/- 1 and 20 +/- 1 years from onset). Out of the
identified patients, 66.3% remained benign at 20 years; however, by changing the
definition for benign to EDSS <=2 or <=1 at 10 years, they increased to 71.9 and
81.6%, respectively. Female sex, EDSS <=1 at 10 years, and a pure sensory onset
were associated with a benign course, while a pure motor onset with an NLB
condition. According to multivariate analysis, an EDSS <=2 at 10 years predicted
a long-term benign course. Our study questions the current definition of "benign"
MS, suggesting a more stringent EDSS cutoff at 10 years to predict long-term
benign prognosis.
PMID- 28417193
TI - Genome-wide analysis of VQ motif-containing proteins in Moso bamboo
(Phyllostachys edulis).
AB - MAIN CONCLUSION: 29 Moso bamboo VQ proteins were genome-wide identified for the
first time, and bioinformatics analysis was performed to investigate phylogenetic
relationships and evolutionary divergence. The qRT-PCR data show that PeVQ genes
response to different stress treatments. Accumulating evidence suggests that VQ
motif-containing proteins in rice (Oryza sativa), Arabidopsis (Arabidopsis
thaliana), and maize (Zea mays) play fundamental roles in response to various
biotic and abiotic stresses. However, little is known about the functions of VQ
family proteins in Moso bamboo (Phyllostachys edulis). In this study, we
performed a genome-wide bioinformatic analysis and expression profiling of PeVQ
genes. A total of 29 VQ genes was identified and divided into seven subgroups (I
VII) based on phylogenetic analysis. Gene structure and conserved motif analysis
revealed that 25 of 29 VQ genes contained no introns. Multiple sequence alignment
showed that Moso bamboo VQ motif-containing proteins contained five variations of
the conserved motif. The time of duplication and divergence of Moso bamboo from
rice and maize was calculated using K s analysis. A heat map was generated using
microarray data from 29 Moso bamboo VQ genes suggesting that these genes were
expressed in different tissues or developmental stages. Quantitative real-time
PCR (qRT-PCR) and promoter analysis indicated that PeVQ genes were differentially
regulated following treatment with polyethylene glycol, abscisic acid and
salicylic acid. Our results provide a solid foundation for further research of
the specific functions of VQ motif-containing proteins in Moso bamboo.
PMID- 28417194
TI - Impact of BCL2 polymorphisms on survival in transitional cell carcinoma of the
bladder.
AB - PURPOSE: To evaluate the impact of three BCL2 single-nucleotide polymorphisms,
i.e., c.-938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on
survival in patients with transitional cell carcinoma of the bladder. METHODS: We
analyzed 179 patients who underwent surgical treatment for bladder cancer at the
Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted
and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was
performed. Kaplan-Meier and Cox regression analyses were used to determine the
putative impact of the three polymorphisms on outcome. RESULTS: c.-938C>A and
c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D' 0.96). We
found a significant association between c.-938C>A and relapse-free survival (p =
0.024) with an allele dose effect. In the same way, c.21G>A had a significant
impact on both relapse-free survival (p = 0.009) and progression-free survival (p
= 0.012), as well as a pronounced allele dose effect. Regression analysis proved
c.21G>A and c.-938C>A, to be an independent risk factor in univariate and
multivariable analyses. CONCLUSIONS: In our cohort, both c.-938C>A and c.21G>A
showed a significant impact on outcome with TCC of the bladder. Due to the
linkage disequilibrium of both SNPs, maybe, only one of them could mediate this
effect. In multivariable analysis, however, both proved to be independently
associated with overall survival. Contrary to other findings which found the c.
938C>A mainly influencing outcome, our data may suggest that the main effect on
TCC could be due to the c.21G>A polymorphism.
PMID- 28417195
TI - RRx-001 protects against cisplatin-induced toxicities.
AB - PURPOSE: RRx-001, a minimally toxic tumor-associated macrophage and neutrophil
repolarizing agent, is under investigation in Phase II clinical trials as a
sensitizer/resensitizer to cisplatin and carboplatin. On the basis of anecdotal
clinical observations of improved platinum tolerability following a priming
period with RRx-001 as well as preclinical studies that have previously
demonstrated radioprotection of intestinal stem cells and cardioprotection from
doxorubicin, the in vivo cytoprotective potential of RRx-001 pretreatment against
cisplatin-induced bone marrow suppression and renal toxicity was investigated.
METHODS: BALB/c mice were divided into three groups: (1) no treatment, (2)
vehicle and cisplatin only, and (3) RRx-001 and cisplatin. RRx-001 treatment (5
mg/kg every other day for 3 days) was initiated 3 days prior to cisplatin
administration. Blood was collected from the femoral vein at different intervals
to measure total hemoglobin and leukocyte counts as well as renal functional
markers (serum urea, creatinine and creatinine clearance). Metaphase spreads were
prepared from whole bone marrow cells as markers of clastogenicity. RESULTS: RRx
001 pretreatment significantly decreased (P < 0.05) the blood urea nitrogen and
creatinine levels. A statistically significant (P < 0.05) reduction in the mean
total chromosome aberration frequency per metaphase in the RRx-001 and cisplatin
group compared to the cisplatin-only group was observed. CONCLUSIONS: This study
is the first to demonstrate that RRx-001 has nephro-, geno- and myeloprotective
effects in vivo. Importantly, RRx-001 did not protect sarcoma-180 solid tumor
xenografts against cisplatin-induced cytotoxicity. These results potentially
support the use of RRx-001 as a chemoprotector against cisplatin-induced
toxicities.
PMID- 28417196
TI - A sustaining rod increases necrosis of loop ileostomies: a randomized controlled
trial.
AB - PURPOSE: Defunctioning loop ileostomies (LI) are commonly used in colorectal
surgery to reduce the potentially detrimental consequences of anastomotic
leakages. However, stoma-related morbidity is high with up to 75% of patients
having local complications. The aim of this study was to investigate the effect
of a sustaining rod on the local complication rate. METHODS: In this prospective,
multi-center, randomized controlled trial, subjects were allocated to either a
rod or a rod-less protocol (NCT00959738). The primary outcome was local morbidity
as measured by a stoma specific morbidity score (SSMS) during the first 3 months
postoperatively. RESULTS: Between August 2008 and July 2014, a total of 122
patients were enrolled in the study, of which 78 (63.8%) completed the study [44
(56.4%) rod, 34 (43.6%) rod-less]. There was no significant difference in the
SSMS between the two groups. The incidence of necrosis or partial necrosis,
however, was significantly increased in the rod group: 13 (29.5%) vs. 1 (2.9%) in
the rod-less group (p < 0.01). The retraction rate did not differ significantly
between the groups: two (4.5%) in the rod vs. five (14.7%) in the rod-less group
(p = 0.13). High body mass index (BMI > 26) was associated with an odds ratio of
5 (p < 0.01) for severe stoma complications. CONCLUSIONS: A rod-less technique
for loop ileostomies reduces the risk of stomal necrosis, with a high BMI being
an independent risk factor for stomal complications.
PMID- 28417197
TI - Origin, Function, and Fate of Metallothionein in Human Blood.
AB - Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS),
infections, and temperature are well-known metallothionein (MT) inducers in human
blood. The current review aims to summarize synthesis, function, and fate of
human blood MT in response to the known MT inducers. Part of the MTs that are
synthesized in different organs such as the liver, kidney, and spleen is
transported and stored in different blood cells and in plasma. Cells of the
circulatory system also synthesize MT. From the circulation, MT returns to the
kidney where the metal-bound MTs are degraded to release the metal ion that in
turn induces MT expression therein. The blood MTs play important roles in metal
detoxification, transportation, and storage. By neutralizing ROS, MTs protect
blood cells from oxidative stress-induced cytotoxicity and genotoxicity.
Arguably, MTs are also involved in immune suppression. Given the permeating
distribution of blood MT throughout the body as well as its diverse role in the
protection against harmful environmental factors and in metal homeostasis, MT
could be better recognized as a major public health protein.
PMID- 28417198
TI - Biases in the production and reception of collective knowledge: the case of
hindsight bias in Wikipedia.
AB - The Web 2.0 enabled collaboration at an unprecedented level. In one of the
flagships of mass collaboration-Wikipedia-a large number of authors socially
negotiate the world's largest compendium of knowledge. Several guidelines in
Wikipedia restrict contributions to verifiable information from reliable sources
to ensure recognized knowledge. Much psychological research demonstrates,
however, that individual information processing is biased. This poses the
question whether individual biases translate to Wikipedia articles or whether
they are prevented by its guidelines. The present research makes use of hindsight
bias to examine this question. To this end, we analyzed foresight and hindsight
versions of Wikipedia articles regarding a broad variety of events (Study 1). We
found the majority of articles not to contain traces of hindsight bias-contrary
to prior individual research. However, for a particular category of events
disasters-we found robust evidence for hindsight bias. In a lab experiment (Study
2), we then examined whether individuals' hindsight bias is translated into
articles under controlled conditions and tested whether collaborative writing-as
present in Wikipedia-affects the resultant bias (vs. individual writing).
Finally, we investigated the impact of biased Wikipedia articles on readers
(Study 3). As predicted, biased articles elicited a hindsight bias in readers,
who had not known of the event previously. Moreover, biased articles also
affected individuals who knew about the event already, and who had already
developed a hindsight bias: biased articles further increased their hindsight.
PMID- 28417199
TI - Intake of 7,8-dihydroxyflavone from pregnancy to weaning prevents cognitive
deficits in adult offspring after maternal immune activation.
AB - Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor,
tropomyosin receptor kinase B (TrkB) signaling plays a key role in the brain
neurodevelopment. The exposure of pregnant mice to polyinosinic-polycytidylic
acid [poly(I:C)] causes cognitive deficits in adult offspring. Supplementation
with a TrkB agonist, 7,8-dihydroxyflavone, in poly(I:C)-treated pregnant mice
from pregnancy to weaning could prevent the onset of cognitive deficits and
reduced BDNF-TrkB signaling in the prefrontal cortex of their adult offspring.
These findings suggest that supplementation with a TrkB agonist in pregnant women
with an ultra-high risk of psychosis may reduce the development of psychosis in
their offspring.
PMID- 28417200
TI - HPV-related carcinomas of the head and neck: morphologic features, variants, and
practical considerations for the surgical pathologist.
AB - Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma is a
distinct tumor entity with clinical, epidemiologic, genetic, histologic,
prognostic, and treatment differences from smoking- and alcohol-related head and
neck squamous cell carcinoma. This is now well known by the pathology and medical
community. What is not yet widely known is that several emerging variants of HPV
related carcinoma of the head and neck exist apart from the prototypical non
keratinizing morphology. Further, there is currently considerable variation in
methodologies used and clinical scenarios in which to test for HPV-related head
and neck squamous cell carcinoma, and no standard approach has emerged. In this
article, we will review the morphology of prototypical HPV-related squamous cell
carcinoma of the oropharynx and other HPV-related variants of head and neck
carcinoma with an emphasis on their differential diagnosis, grade, and prognosis,
as well as outline the current best practices for testing for HPV in head and
neck carcinomas.
PMID- 28417201
TI - Quantification of dynamic posterior translation in modified bilateral Alexander
views and correlation with clinical and radiological parameters in patients with
acute acromioclavicular joint instability.
AB - INTRODUCTION: Classification of AC-joint instability is based on radiologic
evaluation of anteroposterior (a.p.) stress views of both shoulders, neglecting
the horizontal component of instability. Recent studies have proposed an
association of dynamic posterior translation (DPT) and inferior clinical results.
The purpose of this study was to quantify DPT in modified Alexander views and
correlate it with other radiological and clinical data. MATERIALS AND METHODS:
Thirty-two patients (4 f, 28 m, mean age 34.1) with acute AC-joint dislocation
(16 = RW III, 16 = RW V) underwent radiological examination including bilateral
a.p. stress views with measurement of the coracoclavicular distance (CCD) and
bilateral modified Alexander views with different approaches to quantify DPT
(overlapping area OAAC, overlapping length OLAC). In addition, the Constant
Score, Subjective Shoulder Value, Taft Score (TF), and the Acromioclavicular
Joint Instability Score (ACJI) were obtained. RESULTS: In Rockwood (RW) type III
injuries, a mean CCD of 15.8 (9.8-22.8) mm, OAAC of 50.9 (0-216.6) mm2, and OLAC
of 6.5 (-4.7-17.9) mm were found. RW V patients showed a CCD of 23.1 (13.7-32.0)
mm; OAAC 7.0 (0-92.3) mm2; and OLAC -4.8 (-19.6-9.8) mm. Particularly in RW III
the CCD, OAAC and OLAC revealed significant correlation with the ACJI (r =
0.64/r = 0.72/r = 0.68, p < 0.05) and TF (r = -0.56/r = 0.68/r = 0.51, p < 0.05).
The proposed quantification tools for DPT were found to have a moderate-to-strong
correlation with the score results, especially with AC-joint specific scores. RW
type V injuries had a moderate correlation with clinical parameters (OAAC with
ACJI: r = 0.44, p > 0.05 and OLAC with TF: r = -0.45, p > 0.05). CONCLUSIONS:
Measuring the OLAC is a convenient way for quantifying DPT in modified Alexander
views. It showed significant correlation with clinical scores, indicating the
relevance of DPT in patients with AC-joint injury.
PMID- 28417202
TI - Cardiorespiratory fitness and muscle strength in pancreatic cancer patients.
AB - PURPOSE: Cancer patients frequently experience reduced physical fitness due to
the disease itself as well as treatment-related side effects. However, studies on
physical fitness in pancreatic cancer patients are missing. Therefore, we
assessed cardiorespiratory fitness and muscle strength of pancreatic cancer
patients. METHODS: We included 65 pancreatic cancer patients, mostly after
surgical resection. Cardiorespiratory fitness was assessed using cardiopulmonary
exercise testing (CPET) and 6-min walk test (6MWT). Hand-held dynamometry was
used to evaluate isometric muscle strength. Physical fitness values were compared
to reference values of a healthy population. Associations between
sociodemographic and clinical variables with patients' physical fitness were
analyzed using multiple regression models. RESULTS: Cardiorespiratory fitness
(VO2peak, 20.5 +/- 6.9 ml/min/kg) was significantly lower (-24%) compared to
healthy reference values. In the 6MWT pancreatic cancer patients nearly reached
predicted values (555 vs. 562 m). Maximal voluntary isometric contraction (MVIC)
of the upper (-4.3%) and lower extremities (-13.8%) were significantly lower
compared to reference values. Overall differences were larger in men than those
in women. Participating in regular exercise in the year before diagnosis was
associated with greater VO2peak (p < .05) and MVIC of the knee extensors (p <
.05). CONCLUSIONS: Pancreatic cancer patients had significantly impaired physical
fitness with regard to both cardiorespiratory function and isometric muscle
strength, already in the early treatment phase (median 95 days after surgical
resection). Our findings underline the need to investigate exercise training in
pancreatic cancer patients to counteract the loss of physical fitness.
PMID- 28417204
TI - Injuries to the Chopart joint complex: a current review.
AB - Chopart complex injuries (CCIs) are thought to be uncommon; however, recent
literature states the rate of misdiagnosis to be between 20 and 41%. Chopart
complex injuries are not ankle injuries, with which they are initially confused
due to a similar mechanism of trauma in many cases. Injury to the Chopart complex
commonly affects multiple structures. The key to optimal treatment is a high
index of clinical suspicion combined with timely accurate imaging studies.
Careful diagnostic workup with high-quality radiographs of the foot in neutral
position should be obtained. Computed tomography (CT) and/or magnetic resonance
imaging (MRI) are recommended to accurately assess bone and soft tissue injury.
CCI frequently leads to prolonged swelling, pain and disability. In some cases,
it may result in a posttraumatic flatfoot deformity.
PMID- 28417203
TI - Effects of diet and exercise on weight-related outcomes for breast cancer
survivors and their adult daughters: an analysis of the DAMES trial.
AB - PURPOSE: Few trials have aimed to promote diet and exercise behaviors in both
cancer survivors and their family members and examine their associations with
weight-related outcomes. We conducted a secondary analysis to examine
associations between change in diet and exercise behaviors and weight-related
outcomes for overweight breast cancer survivors and their overweight adult
daughters in the Daughters And MothErS Against Breast Cancer (DAMES) randomized
trial. METHODS: The DAMES trial assessed the impact of two iteratively tailored,
mailed print diet and exercise interventions against standard brochures over a 12
month period. This analysis examined change in diet and exercise behaviors and
weight-related variables from baseline to post-intervention for the 50 breast
cancer survivors and their adult daughters randomized to the intervention arms.
To reduce the potential for type II error in this pilot, p values <0.10 were
considered statistically significant. RESULTS: For mothers, change in diet
quality was uniquely related to change in BMI (beta = -0.12, p = 0.082), weight
(beta = -0.12, p = 0.060), and waist circumference (beta = -0.38, p = 0.001),
whereas change in caloric intake was related to waist circumference (beta = 0.21,
p = 0.002). For daughters, change in caloric intake was related to change in
waist circumference (beta = 0.12, p = 0.055). However, change in diet quality was
not associated with weight-related outcomes in daughters. Additionally, change in
exercise was not associated with weight-related outcomes in mothers or daughters.
CONCLUSIONS: Findings support mail-based and other tailored interventions for
weight loss in this population, with an emphasis on diet quality for breast
cancer survivors and caloric intake for their adult daughters.
PMID- 28417205
TI - An eclosion hormone-like gene participates in the molting process of Palaemonid
shrimp Exopalaemon carinicauda.
AB - Molting behavior is an important physiological process related to metamorphosis,
growth, and reproduction in crustaceans. Previous studies indicated that the
molting process was controlled by 20-hydroxyecdysone (20E) and upstream hormones,
peptides, and environmental factors, which regulate 20E function. Eclosion
hormone (EH) in insect is a kind of neuropeptide that is regulated by 20E and
triggers ecdysis behavior at the end of molting process. However, the function of
eclosion hormone gene during the molting process in crustaceans is still largely
unknown. In the present study, an eclosion hormone-like gene EcEHL was identified
from Exopalaemon carinicauda. The deduced amino acid sequence of EcEHL contained
a signal peptide, a typical eclosion domain, and six conserved cysteine residues
forming three putative disulfide bonds. EcEHL was predominantly expressed in the
epidermis, gill, and eyestalk of shrimp. In situ hybridization analysis showed
that EcEHL transcripts were localized in gill cells and in medulla externa X
organ, medulla terminalis X-organ, sinus gland, and lamina ganglionaris of
eyestalks. During the molting process of shrimp, EcEHL showed the highest
expression level in shrimp at the premolt stage. The expression level of EcEHL in
shrimp at mid premolt stage was up-regulated by injection of exogenous 20E.
Silencing of EcEHL using double-stranded RNA delayed both the molting process and
ecdysis rate of E. carinicauda. Furthermore, injection of exogenous 20E to shrimp
at mid premolt stage (D2) could remarkably speed up the molting process and also
raise the ecdysis rate of E. carinicauda. The results revealed that EcEHL might
participate in the molting process of shrimp and its expression was regulated by
20E. These data will help us to understand the molecular mechanism of molting in
crustacean.
PMID- 28417206
TI - Erratum to: Effect of the addition of nano-sized sodium hexametaphosphate to
fluoride toothpastes on tooth demineralization: an in vitro study.
PMID- 28417207
TI - Impact of food processing on rye product properties and their in vitro digestion.
AB - PURPOSE: Rye products have been reported to elicit postprandial insulin and
glucose responses which may be beneficial for prevention of type-2 diabetes.
However, mechanisms underlying variations in responses related to processing
techniques are not fully understood. METHODS: Five differently processed rye
products (sourdough-fermented bread, fermented and unfermented crispbread,
extrusion-cooked rye, and porridge) and refined wheat bread were characterised.
Two in vitro methods, a dynamic method simulating digestion in the stomach and
small intestine and a static method, simulating conditions in the stomach were
used to determine viscosity development, structural changes and release of
glucose during digestion. RESULTS: Structural and compositional differences
induced by processing influenced product digestion. Gastric disintegration and
digesta particle size were related to characteristics of the starch/protein
matrix, while digesta viscosity was reduced due to fibre degradation during
fermentation. More cohesive boluses were associated with slower glucose release.
Sourdough fermentation increased amylose leakage and appeared to inhibit starch
hydrolysis despite low digesta viscosity and rapid disintegration. CONCLUSIONS:
The net release of glucose during digestion of foods is determined by several
factors which may vary in their importance depending on product specific
properties.
PMID- 28417208
TI - Aesthetic Shoulder Augmentation with Silicone Implants.
AB - BACKGROUND: Men with narrower shoulders may appear less muscular than other men.
Deltoid muscle underdevelopment or atrophy, a condition commonly linked to narrow
shoulder issues, may be associated with congenital deformity, trauma, or
neoplasm. For some people, regular exercise does not effectively develop the
deltoid muscle region. Some people naturally have a smaller build than others.
Even with developed deltoid muscles, these people still appear to be small. The
authors have performed lateral shoulder augmentation with silicone implants for 4
years. Based on their experience, this procedure stands as a reliable solution
for men with narrow shoulders. METHODS: Lateral shoulder augmentation with
silicone implants was developed and used for 81 patients between April 2009 and
April 2013. None of the patients had shoulder deformities except for two patients
(one patient with Poland's syndrome and one patient with Sprengel's deformity).
The implants were placed through a horizontal axillary crease incision in a plane
dissected between the deltoid fascia and muscle. RESULTS: All augmentation or
correction procedures have been met with complete patient approval. Five patients
had minor complications such as hematoma and implement displacement. However, all
these complications were resolved to the satisfaction of the patients.
CONCLUSION: When silicone implants are used to achieve purely aesthetic
improvements, successful shoulder augmentation procedures are observed. LEVEL OF
EVIDENCE IV: This journal requires that authors assign a level of evidence to
each submission to which Evidence-Based Medicine rankings are applicable. This
excludes Review Articles, Book Reviews, and manuscripts that concern Basic
Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors http://www.springer.com/00266 .
PMID- 28417211
TI - Helminth Diversity in Synanthropic Rodents from an Urban Ecosystem.
AB - Richness and diversity of parasites depend on a set of interrelated factors
related to the characteristics of the host, the environment and the parasites
itself. In the City of Buenos Aires, rodent communities vary according to
landscape structure. The goal of this paper was to study the variations of
helminth richness and diversity among invasive rodent species in different
landscape units of the City of Buenos Aires. 73% of the rodents were parasitized
with at least one of the 10 identified helminth species. Each rodent species
presented its own characteristics in terms of richness, diversity and helminth
composition, keeping these characteristics still occupying more than one
landscape unit. The infracommunities with greater diversity corresponded to R.
norvegicus due to its high values of parasitic richness, proportion of infected
hosts and parasite prevalence. Instead, R. rattus and M. musculus
infracommunities had lower diversity since a high percentage of them presented a
unique helminth species. Within the city, the inhabitants of shantytowns would be
the most exposed to zoonotic diseases transmitted by rodents due to high
abundance of rodents harboring a high parasite load, including species like
Hymenolepis nana and H. diminuta, recognized worldwide from a zoonotic aspect.
PMID- 28417212
TI - LALF32-51-E7 therapeutic vaccine induces antitumor immunity against human
papillomavirus type 16 E7-expressing murine tumor metastases in the lungs.
AB - One important goal of cancer immunotherapy is to prevent and treat tumor
metastasis. We have previously reported the significant antitumor effect induced
by the immunization with our human papillomavirus therapeutic protein-based
vaccine (LALF32-51-E7) without adjuvant and admixed with clinically relevant
adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study,
we evaluated the efficacy of the above mentioned vaccine formulations in
controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic
clone named TC-1* and other intravenous injection site less stressful than the
tail vein. We generated a lung metastasis model by injecting TC-1* cells into the
retro-orbital venous sinus and this is the first study describing it. Also, this
is the first study that demonstrates the efficacy of the immunization with LALF32
51-E7 without adjuvant and admixed with VSSP or Al(OH)3 in controlling metastatic
tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be
used to test the efficacy of other immunotherapeutic strategies based on E6/E7
antigens.
PMID- 28417213
TI - Retrospective analysis of cervical corpectomies: implant-related complications of
one- and two-level corpectomies in 45 patients.
AB - Cervical corpectomies are increasingly used to treat degenerative, metastatic,
inflammatory and traumatic multisegmental diseases. The postoperative results are
thought to correlate mainly with the number of resected vertebral bodies. Thus,
the aim of the study was to analyse complications and early outcome of these
procedures to document the implant-related complications in order to set up a
prospective clinical trial. Forty-five patients, who were treated in our
department from 2011 to 2014 and who were available for a minimum follow-up of 1
year, were consecutively included in this retrospective evaluation. The median
age was 61 (+/-11) years with a female to male sex ratio of 19 to 26,
respectively. In these patients, cervical corpectomies (one-, two- and three
level procedures) were performed. The average number of resected levels was 1.2
levels. The intraoperative loss of blood (LOB), the red cell transfusions (rcT),
the length of operation (LOO) and the usage of drains were investigated and
correlated with intra- and postoperative complications. The mean LOO was 244 min
(+/-68) with a mean LOB of 511 ml (+/-531). The overall complication rate was
22.9% (10 patients). Six patients (13.3%) had implant-related complications due
to loosening and toggling of the screws and/or cage subsidence. Two patients
(4.4%) had a postoperative haematoma and another two patients (4.4%) suffered
from neurological deterioration due to an ongoing and severe myelopathic
syndrome. All these patients received revision surgery. The average time from the
first to revision surgery was 90 days. Cervical corpectomies still remain
procedures with a high complication rate mainly represented by implant-related
failures. These implant-related complications range from screw/plate loosening or
toggling to graft dislocation with subsidence and might be associated with
constructs extended to the C7 vertebral body. In our study population, the rate
of implant failure was comparable to the literature, but not obviously correlated
with the number of vertebral bodies resected. This may be attributed to the
different disease entities. Thus, our results support the use of circumferential
approaches for selected instability scenarios (metastatic or inflammatory
diseases, kyphosis, osteoporosis, etc.) of one- and two-level corpectomies.
PMID- 28417214
TI - Neural Processes Associated with Vocabulary and Vowel-Length Differences in a
Dialect: An ERP Study in Pre-literate Children.
AB - Although familiarity with a language impacts how phonology and semantics are
processed at the neural level, little is known how these processes are affected
by familiarity with a dialect. By measuring event-related potentials (ERPs) in
kindergarten children we investigated neural processing related to familiarity
with dialect-specific pronunciation and lexicality of spoken words before
literacy acquisition in school. Children speaking one of two German dialects were
presented with spoken word-picture pairings, in which congruity (or the lack
thereof) was defined by dialect familiarity with pronunciation or vocabulary. In
a dialect-independent control contrast, congruity was defined by audio-visual
semantic (mis)match. Congruity effects and congruity-by-dialect group
interactions in the ERPs were tested by data-driven topographic analyses of
variance (TANOVA) and theory-driven focal analyses. Converging results revealed
similar congruity effects in the N400 and late-positive-complex (LPC) in the
control contrast for both dialect groups. In the dialect-specific vocabulary
contrast, topographies of the N400- and LPC-effects were reversed depending on
familiarity with the presented dialect words. In the dialect-specific
pronunciation contrast, again a topography reversal was found depending on
dialect familiarity, however, only for the LPC. Our data suggest that neural
processing of unfamiliar words, but not pronunciation variants, is characterized
by semantic processing (increased N400-effect). However, both unfamiliar words
and pronunciation variants seem to engage congruity judgment, as indicated by the
LPC-effect. Thus, semantic processing of pronunciation in dialect words seems to
be rather robust against slight alterations in pronunciation, like changes in
vowel duration, while such alterations may still trigger subsequent control
processes.
PMID- 28417215
TI - The atrophy and laterality of the hippocampal subfields in parents with or
without posttraumatic stress disorder who lost their only child in China.
AB - Investigating hippocampal subfields may provide new and important insights into
the pathophysiology of posttraumatic stress disorder (PTSD). However, no study
has examined the hippocampal subfield volume changes in parents with or without
PTSD who had lost their only child and could no longer conceive in China. Fifty
seven parents with PTSD (PTSD+), 11 trauma-exposed parents without PTSD (PTSD-),
and 39 non-traumatized controls were recruited to examine the hippocampal
subfield volumes using magnetic resonance imaging. Correlations of the volumes
with the time since trauma and Clinician-Administered PTSD Scale (CAPS) scores
were investigated in the PTSD+ group. The volumes of the bilateral cornu ammonis
(CA) 2-3, CA4-dentate gyrus (DG), and left subiculum were significantly smaller
in the PTSD+ and PTSD- groups than in the controls, but there were no significant
differences between the PTSD+ and PTSD- groups. Additionally, the left CA2-3 and
CA4-DG volumes reduced more than those on the right side in the PTSD+ and PTSD-
groups. The subfield volumes were not related to the time since trauma and the
CAPS scores in the PTSD+ group. In conclusion, hippocampal subfield volumes
decreased in parents who lost their only child with or without PTSD, and the
volumetric reduction may be independent of PTSD and trauma-related. Moreover, the
hippocampal volume deficits showed laterality that the left side was affected
more than the right, and the hippocampal subfields may show differential
vulnerabilities to trauma/PTSD, with the CA2-3 and CA4-DG subfields more
sensitive than others.
PMID- 28417217
TI - Levels of cystatin C in low- and high-flux hemodialysis in children with end
stage renal disease.
AB - BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the
glomerulus and almost completely reabsorbed by the proximal tubules. The aim of
this study was to evaluate serum CyC and its reduction ratio as a biomarker for
assessing the adequacy of the hemodialysis (HD) sessions in children with end
stage renal disease on maintenance HD. We also compared levels of CyC in patients
on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were
included in the study and divided into two groups, with one group (16 patients)
receiving HFH and the other group receiving LFH (24 patients) (high-flux and low
flux polysulfone filters, respectively). Before and after each dialysis session
serum CyC and beta-2-microglobulin (B2M) levels were measured using an ELISA
technique, and routine laboratory tests were performed for each patient. RESULTS:
Pre-dialytic levels of CyC were significantly lower in the patients receiving HFH
than in those receiving LFH (7.33 +/- 1.35 vs. 9.73 +/- 0.93, respectively; p <
0.0001). In the HFH group, post-dialytic levels of serum CyC were significantly
lower than pre-dialytic levels (4.49 +/- 0.71 vs. 7.33 +/- 1.35, respectively; p
< 0.0001). The reduction ratio (RR) of CyC was significantly higher in the HFH
group than in the LFH group (38.2 +/- 3.91 vs. -6.49 +/- 5.05, respectively; p <
0.0001). Serum CyC level significantly correlated with B2M, urea and creatinine
levels in both the LFH and HFH groups, whereas its RR significantly correlated
with the RRs of urea, creatinine, and B2M in the HFH group. CONCLUSION: The
results of our study emphasize the role of CyC as a good marker for assessing the
adequacy of HD sessions in children on HFH and show that the CyC RR may be used
as an index of middle-molecule toxin clearance following HFH sessions.
PMID- 28417219
TI - Treatment effect of methylphenidate on intrinsic functional brain network in
medication-naive ADHD children: A multivariate analysis.
AB - Methylphenidate is a first-line therapeutic option for treating attention
deficit/hyperactivity disorder (ADHD); however, elicited changes on resting-state
functional networks (RSFNs) are not well understood. This study investigated the
treatment effect of methylphenidate using a variety of RSFN analyses and explored
the collaborative influences of treatment-relevant RSFN changes in children with
ADHD. Resting-state functional magnetic resonance imaging was acquired from 20
medication-naive ADHD children before methylphenidate treatment and twelve weeks
later. Changes in large-scale functional connectivity were defined using
independent component analysis with dual regression and graph theoretical
analysis. The amplitude of low frequency fluctuation (ALFF) was measured to
investigate local spontaneous activity alteration. Finally, significant findings
were recruited to random forest regression to identify the feature subset that
best explains symptom improvement. After twelve weeks of methylphenidate
administration, large-scale connectivity was increased between the left fronto
parietal RSFN and the left insula cortex and the right fronto-parietal and the
brainstem, while the clustering coefficient (CC) of the global network and nodes,
the left fronto-parietal, cerebellum, and occipital pole-visual network, were
decreased. ALFF was increased in the bilateral superior parietal cortex and
decreased in the right inferior fronto-temporal area. The subset of the local and
large-scale RSFN changes, including widespread ALFF changes, the CC of the global
network and the cerebellum, could explain the 27.1% variance of the ADHD Rating
Scale and 13.72% of the Conner's Parent Rating Scale. Our multivariate approach
suggests that the neural mechanism of methylphenidate treatment could be
associated with alteration of spontaneous activity in the superior parietal
cortex or widespread brain regions as well as functional segregation of the large
scale intrinsic functional network.
PMID- 28417218
TI - Online support groups for head and neck cancer and health-related quality of
life.
AB - PURPOSE: To investigate the association between using online support groups
(OSGs) and health-related quality of life (HRQoL), and the psychosocial factors
that may influence this association among individuals with head and neck (H&N)
cancer. METHOD: A sample of 199 persons with H&N cancer using four OSGs completed
an online questionnaire using six pre-validated measures for social network, self
efficacy, anxiety and depression, adjustment, empowerment and quality of life. In
addition, socio-demographic as well as illness-related and OSGs-related
information was collected. RESULTS: Participants who had better HRQoL had been
using OSGs for a longer time than those who had worse HRQoL (B = 0.07, p < 0.05).
Depression and adjustment were the only direct mediators in this association,
whereas self-efficacy, anxiety and empowerment appeared as indirect mediators.
CONCLUSION: Participation in OSGs was found to be associated to better HRQoL
either directly or indirectly through decreasing depression, anxiety and the
negative adjustment behaviours and increasing self-efficacy and empowerment of
the users. The study presented a potential model of pathways linking OSG use and
HRQoL for those with H&N cancer. However, the model needs to be tested in future
longitudinal studies and the associations proposed need to be explored in greater
detail.
PMID- 28417220
TI - Synthesis of Naked-eye Detectable Fluorescent 2H-chromen-2-One 2, 6
Dicyanoanilines: Effect of Substituents and pH on Its Luminous Behavior.
AB - A variety of new coumarin derivatives containing C-4 bridged 2,6-dicyanoanilines
(4a-4d) were synthesized via multicomponent one pot approach. These novel sensors
were characterized by spectral analysis and a series of pH sensing fluorescence
studies were performed, the results indicating that the sensors are highly
selective and more effective at various pH. The fluorescence colour changes at
different pH could be directly detected by naked eyes.
PMID- 28417221
TI - Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or
neuromodulators in the enteric nervous system of the porcine esophagus.
AB - Zinc transporter 3 (ZnT3) is one of the zinc transporters family. It is closely
connected to the nervous system, where enables the transport of zinc ions from
the cytoplasm to synaptic vesicles. This substance has been described within the
central and peripheral nervous system, especially in the enteric nervous system
(ENS). The aim of the present study was to describe the co-localization of ZnT3
with selected neuromediators and/or neuromodulators participating in sensory
stimuli conduction in neurons of the ENS within the porcine esophagus. Co
localization of ZnT3 with substance P (SP), leucine enkephalin (LENK) and
calcitonin gene-related peptide (CGRP) was studied using standard double
immunofluorescence technique. The obtained results show that ZnT3, SP and/or LENK
may occur in the same enteric neurons, and the degree of co-localization of these
substances clearly depends on the fragment of esophagus studied and the type of
enteric ganglia. In contrast, the co-localization of ZnT3 with CGRP was not
observed during the present investigation. The obtained results suggest that ZnT3
in the ENS may be involved in the conduction of sensory and/or pain stimuli.
PMID- 28417223
TI - Dorsal metacarpal veins: anatomic variation and potential clinical implications.
AB - The dorsal metacarpal veins are frequently cannulated. Cannulation success is
determined by several variable anatomic features. The objective of this study is
to classify, for the first time, the anatomic variants of the dorsal metacarpal
veins. In this cross-sectional study, 520 university students and staff were
conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied.
Venous visibility was enhanced by either tourniquet application or near-infrared
illumination. Variant patterns of the dorsal metacarpal veins were classified.
The final analysis included 726 hands, for an exclusion rate of 30 %. Eight
pattern types were identified. Three anatomic features informed the variation.
Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants
(83 % of the total). The overall frequency distribution of variants in both hands
was similar (P = 0.8). The frequency distribution of variants was subject to
sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical
variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were
sorted into decreasingly frequent primary, secondary, and tertiary groups. The
groups may signify a progressive increase in difficulty of peripheral
cannulation, in the mentioned order. As such, primary patterns are the most
common and likely the easiest to cannulate, while tertiary patterns are the least
common and likely the most difficult to cannulate. The preceding premise, in
tandem with the bilateral asymmetry of the veins, is clinically significant. With
cannulation difficulty likely signifying an underlying tertiary pattern, the
contralateral dorsal metacarpal veins are probabilistically characterized by a
primary pattern and are, as such, the easier option for peripheral venous
cannulation.
PMID- 28417224
TI - Erratum to: Glutamate and alpha-ketoglutarate: key players in glioma metabolism.
PMID- 28417222
TI - Role of FOXO transcription factors in crosstalk between mitochondria and the
nucleus.
AB - FOXO transcription factors are evolutionally conserved regulators of organismal
life span downstream of insulin signaling. After integrating cellular signals
from various stimuli such as growth factors, oxidative stress, and energy
deprivation, FOXO factors induce expression of a specific set of genes that
regulate various cellular processes to maintain homeostasis at a cellular or
organismal level. In this review, we discuss roles of FOXO proteins in the
maintenance of mitochondria, organelles critical for cellular quality control.
FOXO factors protect mitochondria by activating mitochondrial antioxidant enzymes
and they help remodel damaged mitochondria by inducing remodeling processes such
as mitophagy. Furthermore, we also review the recently identified FOXO-dependent
retrograde signaling from stressed mitochondria to the nucleus, which suggest
that FOXO mediates the crosstalk between these two important organelles to
maintain cell homeostasis. In addition, we introduce a mitohormetic role of
gamitrinib-triphenylphosphonium (G-TPP), a mitochondrial heat shock protein (Hsp)
inhibitor that can induce mild mitochondrial stress to protect cells from future
insults in a FOXO-dependent manner.
PMID- 28417216
TI - Pathogenic mechanisms following ischemic stroke.
AB - Stroke is the second most common cause of death and the leading cause of
disability worldwide. Brain injury following stroke results from a complex series
of pathophysiological events including excitotoxicity, oxidative and nitrative
stress, inflammation, and apoptosis. Moreover, there is a mechanistic link
between brain ischemia, innate and adaptive immune cells, intracranial
atherosclerosis, and also the gut microbiota in modifying the cerebral responses
to ischemic insult. There are very few treatments for stroke injuries, partly
owing to an incomplete understanding of the diverse cellular and molecular
changes that occur following ischemic stroke and that are responsible for
neuronal death. Experimental discoveries have begun to define the cellular and
molecular mechanisms involved in stroke injury, leading to the development of
numerous agents that target various injury pathways. In the present article, we
review the underlying pathophysiology of ischemic stroke and reveal the
intertwined pathways that are promising therapeutic targets.
PMID- 28417225
TI - Comparative proteomic analysis provides insight into 10-hydroxy-2-decenoic acid
biosynthesis in honey bee workers.
AB - 10-Hydroxy-2-decenoic acid (10-HDA) is the major compound produced from the
mandibular glands (MGs) of honey bee workers. However, little information is
available on the molecular mechanisms of 10-HDA biosynthesis. In our study, based
on investigating the 10-HDA secretion pattern and the morphological
characteristics of MGs from honey bee workers of different ages, a comparative
proteomic analysis was performed in the MGs of workers with different 10-HDA
production. In total, 59 up-regulated protein species representing 45 unique
proteins were identified in high 10-HDA-producing workers by 2-DE-MALDI-TOF/TOF
MS. These proteins were involved in carbohydrate/energy metabolism, fatty acid
metabolism, protein metabolism and folding, antioxidation, cytoskeleton,
development and cell signaling. Proteins related to fatty acid metabolism,
including fatty acid synthase and beta-oxidation enzymes, are potentially crucial
proteins involved in 10-HDA biosynthesis pathway. And RNA interference (RNAi)
results demonstrated that knockdown of electron transfer flavoprotein subunit
beta (ETF-beta), one of the protein related to fatty acid metabolism, decreased
10-HDA production of worker bees, suggesting that ETF-beta was necessary for 10
HDA biosynthesis. This study reveals the characteristics of MGs of worker bees at
different developmental stages and proteins associated with 10-HDA biosynthesis,
which provides the first insight into the molecular mechanism of 10-HDA
biosynthesis.
PMID- 28417226
TI - The repertoire of bitter taste receptor genes in canids.
AB - Bitter taste receptors (Tas2rs) play important roles in mammalian defense
mechanisms by helping animals detect and avoid toxins in food. Although Tas2r
genes have been widely studied in several mammals, minimal research has been
performed in canids. To analyze the genetic basis of Tas2r genes in canids, we
first identified Tas2r genes in the wolf, maned wolf, red fox, corsac fox,
Tibetan fox, fennec fox, dhole and African hunting dog. A total of 183 Tas2r
genes, consisting of 118 intact genes, 6 partial genes and 59 pseudogenes, were
detected. Differences in the pseudogenes were observed among nine canid species.
For example, Tas2r4 was a pseudogene in the dog but might play a functional role
in other canid species. The Tas2r42 and Tas2r10 genes were pseudogenes in the
maned wolf and dhole, respectively, and the Tas2r5 and Tas2r34 genes were
pseudogenes in the African hunting dog; however, these genes were intact genes in
other canid species. The differences in Tas2r pseudogenes among canids might
suggest that the loss of intact Tas2r genes in canid species is species
dependent. We further compared the 183 Tas2r genes identified in this study with
Tas2r genes from ten additional carnivorous species to evaluate the potential
influence of diet on the evolution of the Tas2r gene repertoire. Phylogenetic
analysis revealed that most of the Tas2r genes from the 18 species intermingled
across the tree, suggesting that Tas2r genes are conserved among carnivores.
Within canids, we found that some Tas2r genes corresponded to the traditional
taxonomic groupings, while some did not. PIC analysis showed that the number of
Tas2r genes in carnivores exhibited no positive correlation with diet
composition, which might be due to the limited number of carnivores included in
our study.
PMID- 28417227
TI - Intestinal Pseudo-Obstruction as the Presenting Manifestation of Kawasaki
Disease.
PMID- 28417228
TI - A Penalized Likelihood Method for Structural Equation Modeling.
AB - A penalized likelihood (PL) method for structural equation modeling (SEM) was
proposed as a methodology for exploring the underlying relations among both
observed and latent variables. Compared to the usual likelihood method, PL
includes a penalty term to control the complexity of the hypothesized model. When
the penalty level is appropriately chosen, the PL can yield an SEM model that
balances the model goodness-of-fit and model complexity. In addition, the PL
results in a sparse estimate that enhances the interpretability of the final
model. The proposed method is especially useful when limited substantive
knowledge is available for model specifications. The PL method can be also
understood as a methodology that links the traditional SEM to the exploratory SEM
(Asparouhov & Muthen in Struct Equ Model Multidiscipl J 16:397-438, 2009). An
expectation-conditional maximization algorithm was developed to maximize the PL
criterion. The asymptotic properties of the proposed PL were also derived. The
performance of PL was evaluated through a numerical experiment, and two real data
illustrations were presented to demonstrate its utility in psychological
research.
PMID- 28417229
TI - A research agenda for the European Association for Endoscopic Surgeons (EAES).
AB - INTRODUCTION: The European Association of Endoscopic Surgeons (EAES) conducted
this study aiming to identify the top research questions which are relevant to
surgeons in Minimal Access Surgery (MAS). This is in order to promote and link
research questions to the current clinical practice in MAS in Europe. METHODS:
Using a systematic methodology, (modified Delphi), the EAES members and
leadership teams were surveyed to obtain consensus on the top research priorities
in MAS. The responses were categorized and redistributed to the membership to
rate the level of importance of each research question. The data were reported as
the weighted average score with a scale from 1 (lowest agreement) to 5 (highest
agreement). RESULTS: In total, 324 of 2580 (12.5%) of the EAES members and the
leaders responded to the survey and contributed to the final consensus. The
ranked responses over the 80th percentile identified 39 research priorities with
rating ranged from 4.22 to 3.67. The top five highest ranking research priorities
in the EAES were centered on improving training in MAS, laparoscopic surgery for
benign upper gastrointestinal conditions, integration of novel technology in OR,
translational and basic science research in bariatric surgery and investigating
the role of MAS in rectal cancer. CONCLUSION: An EAES research agenda was
developed using a systematic methodology and can be used to focus MAS research.
This study was commissioned by the European Association for Endoscopic Surgery
(EAES).
PMID- 28417230
TI - Retraction Note To: VEGF Silencing Inhibits Human Osteosarcoma Angiogenesis and
Promotes Cell Apoptosis via PI3K/AKT Signaling Pathway.
PMID- 28417231
TI - High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.
AB - Lipid composition determines membrane properties, and cholesterol plays a major
role in this determination as it regulates membrane fluidity and permeability, as
well as induces the formation of coexisting phases and domains in the membrane.
Biological membranes display a very diverse lipid composition, the lateral
organization of which plays a crucial role in regulating a variety of membrane
functions. We hypothesize that, during biological evolution, membranes with a
particular cholesterol content were selected to perform certain functions in the
cells of eukaryotic organisms. In this review, we discuss the major membrane
properties induced by cholesterol, and their relationship to certain membrane
functions.
PMID- 28417232
TI - Healthy cortical development through adolescence and early adulthood.
AB - Adolescence is a period of significant brain changes; however, the effects of age
and sex on cortical development are yet to be fully characterized. Here, we
utilized innovative intrinsic curvature (IC) analysis, along with the traditional
cortical measures [cortical thickness (CT), local gyrification index (LGI), and
surface area (SA)], to investigate how these indices (1) relate to each other and
(2) depend on age and sex in adolescent cortical development. T1-weighted
magnetic resonance images from 218 healthy volunteers (age range 8.3-29.2 years,
M[SD] = 16.5[3.4]) were collected at two sites and processed with FreeSurfer and
Caret software packages. Surface indices were extracted per cortex area (frontal,
parietal, occipital, temporal, insula, and cingulate). Correlation analyses
between the surface indices were conducted and age curves were modelled using
generalized additive mixed-effect models. IC showed region-specific associations
with LGI, SA, and CT, as did CT with LGI. SA was positively associated with LGI
in all regions and CT in none. CT and LGI, but not SA, were inversely associated
with age in all regions. IC was inversely associated with age in all but the
occipital region. For all regions, males had larger cortical SA than females.
Males also had larger LGI in all regions and larger IC of the frontal area;
however, these effects were accounted for by sex differences in SA. There were no
age-by-sex interactions. The study of IC adds a semi-independent, sensitive
measure of cortical morphology that relates to the underlying cytoarchitecture
and may aid understanding of normal brain development and deviations from it.
PMID- 28417233
TI - A posterior-to-anterior shift of brain functional dynamics in aging.
AB - Convergent evidence from task-based functional magnetic resonance imaging (fMRI)
studies suggests a posterior-to-anterior shift as an adaptive compensatory
scaffolding mechanism for aging. This study aimed to investigate whether brain
functional dynamics at rest follow the same scaffolding mechanism for aging using
a large Chinese sample aged from 22 to 79 years (n = 277). We defined a
probability of brain regions being hubs over a period of time to characterize
functional hub dynamic, and defined variability of the functional connectivity to
characterize dynamic functional connectivity using resting-state fMRI. Our
results revealed that both functional hub dynamics and dynamic functional
connectivity posited an age-related posterior-to-anterior shift. Specifically,
the posterior brain region showed attenuated dynamics, while the anterior brain
regions showed augmented dynamics in aging. Interestingly, our analysis further
indicated that the age-related episodic memory decline was associated with the
age-related decrease in the brain functional dynamics of the posterior regions.
Hence, these findings provided a new dimension to view the scaffolding mechanism
for aging based on the brain functional dynamics.
PMID- 28417235
TI - Letter to the Editor concerning "Rehydration of a degenerated disc on MRI
synchronized with transition of Modic changes following stand-alone XLIF" by K.
Kita, T. Sakai, M. Abe, Y. Takata and K. Sairyo (Eur Spine J; 2017.
doi:10.1007/s00586-017-4945-6).
PMID- 28417234
TI - Central lumbar spinal stenosis: natural history of non-surgical patients.
AB - PURPOSE: The aim of the present study was to examine the natural history in
patients with lumbar spinal stenosis. The incidence of surgery for this condition
has increased considerably during the past decades in spite of a fairly favorable
natural history in previous studies. METHODS: 146 consecutive patients with
clinical signs and image findings of lumbar spinal stenosis, who were not
recommended surgical treatment, were followed; the reason as to why surgery was
not recommended was a moderate symptom level. The follow-up rate was 89% after
3.3 years. Group values for comorbidities and diagnostic imaging were comparable
to patients selected for surgery, with the exception of a lower frequency of
degenerative spondylolisthesis among the non-operative patients. The mean age of
those observed was 68 (21-91), and 58% were females. RESULTS: During the
observation period spontaneous improvements were found for pain and health
related quality of life, but not for walking. Using the minimum clinically
important difference for VAS, leg and back pain improved in 32 and 36% of
patients, respectively, were unchanged in 55 and 54%, and worsened in 13 and 10%.
Findings on diagnostic imaging did not influence patient outcome, except for
stenoses with cross-sectional area <0.5 cm2 where spontaneous improvement was not
seen. Revision of the decision not to operate occurred in 10 cases (7%).
CONCLUSIONS: The natural history of LSS with moderate symptom levels rarely shows
symptom deterioration over a median of 3.3 years; in fact, a slight improvement
of symptoms was seen at group levels. The treatment decision was revised for 7%,
and for the rest an increase in pain was seen in 10-13%. The results support
reluctance towards surgery, if the symptom levels are tolerable for the patients.
PMID- 28417238
TI - Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years
and Younger with Unilateral Operable Invasive Breast Cancer.
AB - BACKGROUND: Young women with breast cancer (BC) have an increased risk of
contralateral breast cancer (CBC) compared with older women. This may contribute
to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads
to improved outcomes. METHODS: A prospectively maintained database was reviewed.
Patient and tumor characteristics, survival, and rate of CBC were compared in
women age <=40 years treated for unilateral Stage 1-3 BC from January 2000
through December 2013. RESULTS: Patients ranged in age from 20 to 40 (mean 36)
years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had
unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ
in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the
BCS and BM group had smaller, fewer node-positive (p = 0.02) and lower grade
tumors (p < 0.01) compared with the UM group. With a median follow-up of 79
months, Disease-free survival was similar for patients treated with BM, BCS (p =
0.22), or UM (p = 0.75). OS was significantly worse in the patients treated with
UM (0.02) but was not different between the BCS and BM groups. CBC incidence was
2% (5/263) in patients who underwent BCS or UM, and 0.4% (1/244) in patients
without a germline genetic mutation. CONCLUSIONS: BCS and UM resulted in similar
disease-free survival (DFS) as BM in patients age 40 years and younger with BC.
BCS and BM had similar OS, whereas UM patients had worse OS. Invasive CBC
incidence was less than 0.5% at 10 years in patients without identified germline
genetic mutations.
PMID- 28417237
TI - Assessment of satisfaction based on age and gender in functional and aesthetic
rhinoplasty.
AB - The aim of this study was to assess patients' satisfaction based on gender and
age using the Rhinoplasty Outcomes Evaluation (ROE) post-rhinoplasty from both
functional and aesthetic outcomes. The study design was a prospective
observational study. A total of 103 patients who underwent Rhinoplasty were
prospectively investigated from January 2011 through December 2013 at King
Abdulaziz University Hospital in Riyadh, Saudi Arabia. The sample included 61
males (59.2%) and 42 females (40.7%). The overall mean age was (25.2 +/- 5.9)
years (range 17-48 years). ROE was distributed pre- and post-surgery. The overall
difference in satisfaction was significant (p < 0.0001). The mean satisfaction
difference of function was increased by 21.5%, raising the satisfaction
percentage from 57.1% initially to 78.5% post-surgery (mean -0.215, CI -0.269,
0.161). Satisfaction of shape post-rhinoplasty showed that the mean satisfaction
increased by 31.3% (mean -0.313, CI -0.369, -0.256), which changed the
satisfaction from a mean of 44.2% before surgery to 75.5% post-rhinoplasty (p =
0.000). There was no significant difference in satisfaction between males and
females, nor was there a significant difference in satisfaction among different
age groups (p > 0.05). There was a significant overall increase in patients'
satisfaction from functional and aesthetic outcomes post-surgery based on ROE.
Our study showed that age and gender did not significantly affect satisfaction.
The ROE was a useful tool to implement for assessing the quality-of-life post
rhinoplasty.
PMID- 28417239
TI - Incidental Gallbladder Cancer: Residual Cancer Discovered at Oncologic Extended
Resection Determines Outcome: A Report from High- and Low-Incidence Countries.
AB - BACKGROUND: Gallbladder cancer detected incidentally after cholecystectomy (IGBC)
currently is the most common diagnosis of gallbladder cancer, and oncologic
extended resection (OER) is recommended for tumors classified higher than T1b.
However, the precise prognostic significance of residual cancer (RC) found at the
time of OER has not been well established. This analysis aimed to determine the
prognostic impact of RC found in patients with IGBC undergoing OER. METHODS:
Outcomes for IGBC at a center for a low-incidence country (USA) and a high
incidence country (Chile) between January 1999 and June 2015 were analyzed.
Residual cancer was defined as histologically proven cancer at OER. Predictors of
disease-specific survival (DSS) were analyzed. RESULTS: Of 187 patients, 171
(91.4%) achieved complete resection (R0) at OER. The rates of surgical mortality
and severe morbidity were respectively 1.1 and 9.6%. Of the 187 patients, 73
(39%) had RC. Perineural invasion and/or lymphovascular invasion and T3 stage
were associated with the presence of RC. In both countries, RC was associated
with a significantly shorter median survival (23% vs not reached; p < 0.001) and
lower 5-year DSS rate (19% vs. 74%; p < 0.001) despite R0 resection. In the
multivariable analysis, RC was an independent poor predictor of DSS (hazard ratio
[HR], 4.00; 95% confidence interval [CI], 2.13-7.47; p < 0.001), as were
lymphovascular and/or perineural invasion (HR, 1.95; 95% CI, 1.19-3.21; p =
0.008). CONCLUSIONS: The presence of RC in patients undergoing OER for IGBC is
associated with poor DSS in both high- and low-incidence countries, even when R0
resection is achieved. Residual cancer defines a high-risk cohort for whom
adjuvant therapy may be beneficial.
PMID- 28417240
TI - Development and Validation of the Pretending Orgasm Reasons Measure.
AB - Pretending orgasm is a widespread phenomenon, reported by both men and women. We
report here on the development of a new measure to assess reasons for pretending.
In three studies, using large diverse samples, we obtained a comprehensive list
of reasons for pretending orgasms (Study 1; N = 46) and conducted both
exploratory (Study 2; N = 416) and confirmatory (Study 3; N = 1010) factor
analyses identifying six reasons for pretending an orgasm: feels good, for
partner, not into sex, manipulation/power, insecurity, and emotional
communication. Sexual dysfunction was correlated with frequency of pretending
orgasms for reasons such as insecure, not into sex, for partner, and emotional
communication. Usefulness for future research and clinical implications are
discussed.
PMID- 28417241
TI - Use of Tumor Necrosis Factor Alpha Inhibitors for Inflammatory Bowel Disease
Patients with Concurrent Heart Failure.
AB - BACKGROUND: Prescribing information for tumor necrosis factor alpha (TNFalpha)
inhibitors, a mainstay of treatment for moderate to severe inflammatory bowel
disease (IBD), instructs cautious use in those with heart failure (HF). However,
the limited data behind these warnings are inconclusive and should be weighed
against mounting evidence demonstrating worse cardiac outcomes in active IBD.
AIMS: To assess whether TNFalpha inhibitor use is reduced in patients with IBD
and HF by analyzing physician practice and prescription patterns. METHODS: Using
a Stanford University database, we queried TNFalpha inhibitor prescriptions in
8905 patients with an ICD-9 diagnosis of Crohn's disease or ulcerative colitis.
Detailed chart review analysis was done for patients with a concurrent diagnosis
of HF who were prescribed anti-TNFalpha agents. In addition, we collected survey
data from 25 gastroenterologists on their usage of these drugs for patients with
IBD and HF. RESULTS: TNFalpha inhibitors were prescribed to 10/455 (2.2%) IBD
patients with HF compared to 1265/8450 (15.0%) in IBD patients without HF (p <
0.0001). Of those ten with HF prescribed TNFalpha inhibitors, only one had it
discontinued because of HF exacerbation while on drug. Survey data indicated few
(5/25) providers do not actively avoid TNFalpha inhibitors for those with HF.
CONCLUSIONS: IBD patients with HF are prescribed significantly less TNFalpha
inhibitors than those without HF. The majority of providers are either uncertain
about or actively avoid use of anti-TNFalpha medications for those with HF. The
risks and benefits of anti-TNFalpha use in HF patients must be investigated
further.
PMID- 28417242
TI - Combined use of the multidimensional prognostic index (MPI) and procalcitonin
serum levels in predicting 1-month mortality risk in older patients hospitalized
with community-acquired pneumonia (CAP): a prospective study.
AB - BACKGROUND: Several scores and biomarkers, i.e., procalcitonin (PCT), were
proposed to stratify the mortality risk in community-acquired pneumonia (CAP).
AIM: Evaluating prognostic accuracy of PCT and Multidimensional Prognostic Index
(MPI) for 1-month mortality risk in older patients with CAP. METHODS: At hospital
admission and at discharge, patients were evaluated by a Comprehensive Geriatric
Assessment to calculate MPI. Serum PCT was measured at admission and 1, 3, and 5
days after hospital admission. RESULTS: 49 patients were enrolled. The overall 1
month mortality was 44.5 for 100-persons year. Mortality rates were higher with
the increasing of MPI. In survived patients, MPI at discharge showed higher
predictive accuracy than MPI at admission. Adding PCT levels to admission MPI
prognostic accuracy for 1-month mortality significantly increased. CONCLUSION: In
older patients with CAP, MPI significantly predicted 1 month mortality. PCT
levels significantly improved the accuracy of MPI at admission in predicting 1
month mortality.
PMID- 28417243
TI - Criterion-related validity of self-reported stair climbing in older adults.
AB - INTRODUCTION: Stair climbing is an activity of daily living that might contribute
to increase levels of physical activity (PA). To date, there is no study
examining the validity of climbing stairs assessed by self-report. The aim of
this study was, therefore, to examine the validity of estimated stair climbing
from one question included in a common questionnaire compared to a pattern
recognition activity monitor in older adults. METHODS: A total of 138 older
adults (94 women), aged 65-86 years (70.9 +/- 4.7 years), from the IMPACT65 +
study participated in this validity study. Estimates of stair climbing were
obtained from the European Prospective Investigation into Cancer and Nutrition
(EPIC) PA questionnaire. An objective assessment of stair climbing was obtained
with the Intelligent Device for Energy Expenditure and Activity (IDEEA) monitor.
RESULTS: The correlation between both methods to assess stair climbing was fair
(rho = 0.22, p = 0.008 for PA energy expenditure and rho = 0.26, p = 0.002 for
duration). Mean differences between self-report and the IDEEA were 7.96 +/- 10.52
vs. 9.88 +/- 3.32 METs-min/day for PA energy expenditure, and 0.99 +/- 1.32 vs.
1.79 +/- 2.02 min/day for duration (both Wilcoxon test p < 0.001). Results from
the Bland-Altman analysis indicate that bias between both instruments were -1.91
+/- 10.30 METs-min/day and -0.80 +/- 1.99 min/day, and corresponding limits of
agreement for the two instruments were from 18.27 to -22.10 METs-min/day and from
3.09 to -4.70 min/day, respectively. CONCLUSION: Our results indicate that self
reported stair climbing has modest validity to accurately rank old age
participants, and underestimates both PAEE and its duration, as compared with an
objectively measured method.
PMID- 28417244
TI - Ribociclib: First Global Approval.
AB - Ribociclib is an oral, small-molecule inhibitor of cyclin-dependent kinase (CDK)
4 and 6 that is under development by Novartis for the treatment of cancer. CDKs
play an important role in cell cycle progression and cellular proliferation, and
inhibition of these kinases with ribociclib results in G1 phase cell-cycle
arrest. Ribociclib, in combination with an aromatase inhibitor, was recently
approved in the USA for the first-line treatment of advanced breast cancer and
has been submitted for approval in the EU for this indication. Ribociclib is
undergoing further phase III investigations in breast cancer and is being
evaluated in phase I or II trials for various solid tumour types and
haematological malignancies. This article summarizes the milestones in the
development of ribociclib leading to this first global approval for use as
initial endocrine-based therapy for the treatment of postmenopausal women with
hormone receptor-positive, human epidermal growth factor receptor 2-negative
advanced or metastatic breast cancer.
PMID- 28417245
TI - Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4.
AB - A fixed-dose combination tablet comprising the hepatitis C virus (HCV) NS5A
inhibitor elbasvir and the HCV NS3/4A protease inhibitor grazoprevir
(elbasvir/grazoprevir; ZepatierTM) was recently approved for the treatment of
chronic HCV genotype 1 and 4 infection in the EU and the USA. In phase III
trials, 12 or 16 weeks of treatment with once-daily elbasvir/grazoprevir (fixed
dose tablet or as individual agents), taken with or without ribavirin, generally
provided high rates of sustained virological response at 12 weeks (SVR12) in
treatment-naive and -experienced adult patients with chronic HCV genotype 1a, 1b
or 4 infection, including those with or without compensated cirrhosis, HIV co
infection, inherited blood disorders or chronic kidney disease or patients
receiving opioid agonist therapy or of Japanese origin. Elbasvir/grazoprevir was
generally well tolerated. Thus, elbasvir/grazoprevir, with or without ribavirin,
represents an effective new option for the treatment of adults with chronic HCV
genotype 1 and 4 infection, including a number of difficult-to-treat populations.
PMID- 28417247
TI - Influence of environmental temperature and humidity on questing ticks in central
Spain.
AB - Ticks are important ectoparasites and vectors of the pathogens that cause disease
in humans and animals. At a natural reserve in Ciudad Real (Spain), an
uncontrollable infestation of wild animals with Hyalomma lusitanicum (Koch) has
been reported by some game reserve owners. Many questions about distribution,
abundance, and phenology of this tick in this area remain unanswered. The aim of
this study was to determine if temperature and relative humidity affect the
questing tick's activity in four species of ticks in a meso-Mediterranean area,
especially that of H. lusitanicum. Data for tick populations in six selected
sampling sites every month, between January 2007 and December 2013 were used.
Temperature and humidity values (ground and environmental) were recorded. The
sampling effort, the similarity between sites, and the phenology of the species
were analyzed. Effects of environmental variables on tick's activity were
assessed by general linear models (GLM) whereas the comparative importance of
variables was measured by hierarchical variance partitioning. Hyalomma
lusitanicum represented 96.3% of the four species of ticks collected. Spring and
summer months presented a higher activity of ticks, than autumn and winter
months. In general, humidity variables were negatively related to the activity of
ticks, whereas temperature variables were positively related. Our results suggest
that the highest activity in the area is produced by biological characteristics
of H. lusitanicum; being temperature and humidity the most important
environmental factors influencing the abundance of this species in the region.
PMID- 28417246
TI - Mammalian target of rapamycin (mTOR) as a potential therapeutic target in various
diseases.
AB - Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that
belongs to Phosphatidylinositol-3-kinase related kinase superfamily. The
signaling pathways of mTOR are integrated through the protein complexes of mTORC1
and mTORC2. mTORC1 controls protein synthesis, cell growth, proliferation,
autophagy, cell metabolism, and stress responses, whereas mTORC2 seems to
regulate cell survival and polarity. Dysregulation of the mTOR pathway has been
implicated in the pathophysiology of a number of disease conditions, including
cancer, cardiovascular, neurodegenerative, and various renal diseases. The
hyperactivation of the mTOR pathway leads to increase in cell growth and
proliferation and also has been documented to stimulate tumor growth. Therefore,
investigation of the involvement of mTOR and its downstream pathways in various
diseases intensively preoccupied scientific community. The present review is
focussed on recent advances in the understanding of the mTOR signaling pathway
and its role in health and various diseases.
PMID- 28417248
TI - Ticks and tick-borne pathogens of dogs along an elevational and land-use gradient
in Chiriqui province, Panama.
AB - Systematic acarological surveys are useful tools in assessing risk to tick-borne
infections, especially in areas where consistent clinical surveillance for tick
borne disease is lacking. Our goal was to identify environmental predictors of
tick burdens on dogs and tick-borne infectious agents in dog-derived ticks in the
Chiriqui Province of western Panama to draw inferences about spatio-temporal
variation in human risk to tick-borne diseases. We used a model-selection
approach to test the relative importance of elevation, human population size,
vegetative cover, and change in landuse on patterns of tick parasitism on dogs.
We collected 2074 ticks, representing four species (Rhipicephalus sanguineus, R.
microplus, Amblyomma ovale, and Ixodes boliviensis) from 355 dogs. Tick
prevalence ranged from 0 to 74% among the sites we sampled, and abundance ranged
from 0 to 20.4 ticks per dog with R. sanguineus s.l. being the most commonly
detected tick species (97% of all ticks sampled). Whereas elevation was the best
single determinant of tick prevalence and abundance on dogs, the top models also
included predictor variables describing vegetation cover and landuse change.
Specifically, low-elevation areas associated with decreasing vegetative cover
were associated with highest tick occurrence on dogs, potentially because of the
affinity of R. sanguineus for human dwellings. Although we found low prevalence
of tick-borne pathogen genera (two Rickettsia-positive ticks, no R. rickettsia or
Ehrlichia spp.) in our study, all of the tick species we collected from dogs are
known vectors of zoonotic pathogens. In areas where epidemiological surveillance
infrastructure is limited, field-based assessments of acarological risk can be
useful and cost-effective tools in efforts to identify high-risk environments for
tick-transmitted pathogens.
PMID- 28417249
TI - Virus-vector relationship in the Citrus leprosis pathosystem.
AB - Citrus leprosis has been one of the most destructive diseases of citrus in the
Americas. In the last decade important progress has been achieved such as the
complete genome sequencing of its main causal agent, Citrus leprosis virus C
(CiLV-C), belonging to a new genus Cilevirus. It is transmitted by Brevipalpus
yothersi Baker (Acari: Tenuipalpidae), and is characterized by the localized
symptoms it induces on the leaves, fruits and stems. It occurs in the American
continents from Mexico to Argentina. The virus was until recently considered
restricted to Citrus spp. However, it was found naturally infecting other plants
species as Swinglea glutinosa Merrill and Commelina benghalensis L., and has been
experimentally transmitted by B. yothersi to a large number of plant species.
Despite these advances little is known about the virus-vector relationship that
is a key to understanding the epidemiology of the disease. Some components of the
CiLV-C/B. yothersi relationship were determined using the common bean (Phaseolus
vulgaris L. cv. 'IAC Una') as a test plant. They included: (a) the virus
acquisition access period was 4 h; (b) the virus inoculation access period was 2
h; (c) the latent period between acquisition and inoculation was 7 h; (d) the
period of retention of the virus by a single viruliferous mite was at least 12
days; (d) the percentage of viruliferous individuals from mite colonies on
infected tissues ranged from 25 to 60%. The experiments confirmed previous data
that all developmental stages of B. yothersi (larva, protonymph and deutonymph,
adult female and male) were able to transmit CiLV-C and that transovarial
transmission of the virus did not occur. CiLV-C can be acquired from lesions on
leaves, fruits and stems by B. yothersi. Based on the distribution of lesions
produced by single viruliferous B. yothersi on bean leaves, it is concluded that
they tend to feed in restricted areas, usually near the veins. The short latent
and transmission periods during the larval stage suggest that the CiLV-C/B.
yothersi relationship is of the persistent circulative type.
PMID- 28417250
TI - Impact of surface roughness on Dielectrophoretically assisted concentration of
microorganisms over PCB based platforms.
AB - This article presents a PCB based microfluidic platform for performing a
dielectrophoretic capture of live microorganisms over inter-digitated electrodes
buried under layers of different surface roughness values. Although
dielectrophoresis has been extensively studied earlier over silicon and polymer
surfaces with printed electrodes the issue of surface roughness particularly in
case of buried electrodes has been seldom investigated. We have addressed this
issue through a layer of spin coated PDMS (of various surface roughness) that is
used to cover the printed electrodes over a printed circuit board. The roughness
in the PDMS layer is generally defined by the roughness of the FR4 base which
houses the printed electrodes as well as other structures. Possibilities arising
out of COMSOL simulations have been well validated experimentally in this work.
PMID- 28417251
TI - Irreversible electroporation for the treatment of rabbit VX2 breast cancer.
AB - Irreversible electroporation (IRE) is considered predominantly as a non-thermal
ablative technique that uses electrical fields to permeabilize cell membranes and
lead to cell death. In this study, we evaluated the efficacy of IRE in the rabbit
VX2 breast cancer model. Thirty-five female New Zealand white rabbits were
inoculated against VX2 breast cancer cells. The rabbits were randomly divided
into two groups: a control group of 15 rabbits and an IRE treatment group of 20
rabbits. Treatment and treatment outcome were evaluated by computerized
tomography (CT) scan (plain or contrast enhanced), tumor growth curves and
pathological examination including H&E, TUNEL, PCNA and CD31 staining. All
rabbits in the IRE treatment group experienced successful IRE without obvious
complications except for thoracic major muscle injury. A focused, complete and
well-defined ablation zone where tumor cells have been thoroughly eradicated was
detected by H&E staining, along with increasing TUNEL staining. The expression of
PCNA and CD31 was down-regulated at the periphery of the ablation region. As of
the last follow-up, 10 rabbits (67%) in IRE group demonstrated disease is under
control; 2 rabbits (13%) are in stable condition; 3 rabbits (20%) suffered from
disease progression; the remaining 5 rabbits were sacrificed for pathological
examination halfway through the study. Overall, the efficacy of IRE was
demonstrated by the creation of a complete ablation region, with increased
apoptosis in the ablation zone and decreased proliferation and microvessel
density of tumor tissue at the periphery. IRE is a promising local treatment for
breast cancer.
PMID- 28417252
TI - Effects of Parental Monitoring and Knowledge on Substance Use and HIV Risk
Behaviors Among Young Men Who have Sex with Men: Results from Three Studies.
AB - Young men who have sex with men (YMSM) are disproportionately impacted by
HIV/AIDS and have elevated rates of substance use. Parenting practices, such as
knowledge of child whereabouts and monitoring of behavioral rules, protect
against these outcomes among heterosexual youth. This article examined the
relationship between these parenting practices and substance use and HIV risk
behaviors among YMSM. Data are reported from three similar studies of YMSM:
ChiGuys (ages 14-18), Crew 450 (ages 16-22), and RADAR (ages 16-29). The ChiGuys
and RADAR studies report cross-sectional analyses, whereas Crew 450 reports
latent growth curve analyses. In ChiGuys and Crew 450, participants reported
significantly higher scores for parental knowledge of general activities than
parental knowledge of gay-specific activities. Parental knowledge of general
activities was significantly associated with less binge drinking in both samples
and with condomless sex in the ChiGuys sample. Parental monitoring was
significantly associated with less marijuana use and condomless sex in younger
RADAR participants (16-18 years) and with less drug use in older participants
(>18 years). Findings support the need for further research on the influences of
parents on YMSM health risk behaviors and the value of exploring family- and
parent-interventions to address YMSM health.
PMID- 28417253
TI - Body Image and Condomless Anal Sex Among Sexual Minority Men Living with HIV.
AB - The interaction of body dissatisfaction and appearance investment (importance and
effort ascribed to appearance) in relation to condomless anal sex has not
previously been examined. Body dissatisfaction in the context of varying degrees
of appearance investment may yield divergent sexual risk outcomes. Sexual
minority men living with HIV (N = 105) completed a battery of self-report
measures. A generalized linear model identified a significant interaction [b =
0.08 (95% CI 0.01, 0.16), p = 0.033] such that when appearance investment was
low, body dissatisfaction was associated with fewer condomless anal sex acts;
when appearance investment was high, body dissatisfaction was associated with
increased condomless anal sex.
PMID- 28417254
TI - Whom are we treating with adaptive servo-ventilation? A clinical post hoc
analysis.
AB - BACKGROUND: Recent evidence has shown that adaptive servo-ventilation (ASV) is
contraindicated in patients with predominant central sleep apnea (CSA) and
reduced left ventricular ejection fraction (LVEF <=45%). The objective of this
study was to assess the clinical usage of ASV in patients at the time-point of
the release of a safety warning by type of SDB, breathing pattern and LVEF.
METHODS: Patients of a cardiac and a respirology sleep center, both in Germany,
who received ASV therapy were contacted between May and October 2015.
Retrospective analyses included diagnostic polysomnography, polysomnography with
continuous positive airway pressure prior to ASV initiation and echocardiography.
Treatment emergent CSA was diagnosed after an appropriate treatment period on
CPAP. RESULTS: 285 patients receiving ASV therapy (91 in the cardiac and 194 in
the respirology setting) underwent diagnostic polysomnography. 233 (82%) patients
had severe SDB, 94 (33%) predominant CSA, and 185 (65%) periodic breathing. 20%
(n = 52) of patients had an LVEF of <=45%. The most common indications for ASV
were CSA in heart failure (41%) in the cardiac setting and treatment emergent CSA
(80%) diagnosed after an appropriate period on CPAP in the respirology setting.
The proportion of patients in whom ASV was contraindicated (CSA and LVEF <=45%)
was 16% in the cardiac setting and 9% in the respirology setting. CONCLUSION:
Clinical usage of ASV changed for a small subgroup of patients after release of
the SERVE-HF results. Nevertheless, ASV treatment should be monitored and
evaluated with diligence in the reminder indications.
PMID- 28417255
TI - Lower limb pain among workers: a cross-sectional analysis of the fifth European
Working Conditions Survey.
AB - OBJECTIVE: Develop a model to predict the prevalence of lower limb pain using
indicators of high workplace exposures based on the fifth European Working
Conditions Survey, evaluate its impact and explore its significance for work
related health problems. METHOD: Cross-sectional interview data of 35,372 workers
from 27 countries of the European Union in 2010 (EU27) were used to develop (20%
sample) and validate (80% sample) a logistic regression model for lower limb
pain. Independent variables included descriptions of working conditions,
assessments of physical and psychosocial exposures at work, and demographic
factors. The impact of the model was explored through the amount of lower limb
pain cases attributable to work and estimating work absences correlated with
lower limb pain. RESULTS: The resulting logistic model included ten risks
indicators and one preventive factor. The highest odds ratios (OR) corresponded
to "tiring or painful positions" OR 2.0, 99% confidence interval (99% CI) 1.9
2.2, and "not satisfied with level of working conditions in the job" (OR 1.6, 99%
CI 1.5-1.7). The prevalence of work-related lower limb pain was 16.5% for men and
15.8% for women for the 27 countries of the European Union. Estimates based on
the developed model revealed more than 34 million cases of work-related lower
limb pain, where four physical risks explained about 22 million cases. In
addition, more than 3 million days of absence from work in 2010 could be
attributed to lower limb pain. CONCLUSION: Lower limb pain is highly prevalent
among the European workforce and work exposures are a major contributing factor.
Effective workplace interventions should aim at improving working conditions at
workplaces with multiple risks.
PMID- 28417256
TI - To which extent social withdrawal at the age of 1 year is associated with IQ at 5
6 years old? Results of the EDEN mother-child cohort.
AB - The present study aims to determine to which extent social withdrawal at 1 year
is associated with the child's IQ at the end of the preschool period. Children (N
= 1045) from the EDEN mother-child cohort were assessed for social withdrawal
behaviours at 1 year by trained midwives using the Alarm Distress BaBy (ADBB)
scale. Midwives also examined infants' language and motor development at 1 year.
At the age 5-6 years, IQ scores were based on the WPPSI-III. Linear regression
models were used to determine the association between IQ and ADBB, adjusted for a
broad range of pre- and postnatal environmental factors and for language and
motor skills scores at 1 year. After adjusting for environmental factors,
children with social withdrawal at 1 years (ADBB >=5; N = 195) had significantly
lower IQ scores at 5-6 years (-2.81 IQ points; p value 0.007) compared to
children without social withdrawal (ADBB <5; N = 847). When motor and language
skills at 1 year were included in the previous model, no association between
social withdrawal and IQ at 5-6 years was found. Being socially withdrawn at 1
year is associated with lower IQ scores at 5-6 years. The potential influence of
these developmental aspects on each other (withdrawal behaviour and
language/motor skills) may occur early in development. Our results improve our
understanding of the outcomes of early social withdrawal behaviour and call for
early detection of delay in acquisition of language/motor skills among socially
withdrawn young children.
PMID- 28417257
TI - Additive effect of congenital heart disease and early developmental disorders on
attention-deficit/hyperactivity disorder and autism spectrum disorder: a
nationwide population-based longitudinal study.
AB - In this retrospective nationwide population-based case-control study, we
investigated the impact of congenital heart disease (CHD) on the development of
attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder
(ASD), which remains unclear. Children aged <18 years that were diagnosed with
CHD (n = 3552) between January 1, 1997 and December 31, 2009 were identified from
the National Health Insurance Research Database in Taiwan. Non-CHD controls (n =
14,208) matched for age and sex (1:4) were selected from the same dataset. All
subjects were observed until December 31, 2011 or their death. Comorbid perinatal
conditions and early developmental disorders (EDD) that were diagnosed before
ADHD and ASD diagnosis were also analyzed. The incidence rates of perinatal
comorbidities, EDD, ADHD, and ASD were higher in the CHD group than in the
control group. Multivariate Cox regression analysis revealed that the CHD group
had an increased risk of developing ADHD (adjusted hazard ratio [aHR] 2.52, 95%
confidence interval CI 1.96-3.25) and ASD (aHR 1.97, 95% CI 1.11-3.52) after
adjusting for confounding comorbidities. EDD, but not perinatal comorbidities
were also independent risk factors for ADHD and ASD after adjustment. Subgroup
analysis indicated that the risk for ADHD (HR 16.59, 95% CI 12.17-22.60) and ASD
(HR 80.68, 95% CI 39.96-176.12) was greatly increased in CHD subjects with EDD
than in non-CHD subjects without EDD. These findings suggested that CHD at birth
and EDD during early childhood were two independent risk factors for ADHD and ASD
and that concurrent CHD and EDD might additively increase these risks.
PMID- 28417258
TI - In vivo facial soft tissue depths of a modern adult population from Germany.
AB - Forensic facial reconstruction may be the final option available to draw public
attention in cases where the identity of an individual cannot be established by
standard identification methods. Two fundamental components of all forensic
facial reconstruction techniques are cranial morphology and soft tissue depth
databases. The purpose of this study was to extend such databases by providing a
complete set of accurate facial soft tissue thickness measurements, acquired from
a contemporary adult population from Germany. The material for the study
consisted of 320 (160 male, 160 female) anonymised multi-slice computerised
tomography (MSCT) scans of individuals drawn from a German population. In
Amira(r), 3D models of the surfaces of the skull and the facial skin were semi
automatically segmented using calculated thresholds and surface extraction
algorithms. Facial soft tissue depth was measured at 10 midline and 28 bilateral
anatomical landmarks. The analysis of facial soft tissue thickness versus BMI,
sex and age indicated that, at a number of the landmarks, facial soft tissue
depth is significantly (p < 0.05) influenced by all three biometric variables.
Facial soft tissue thickness increased with increasing BMI. The differences
between males and females were statistically significant (p < 0.05) for almost
all anatomical landmarks with the exception of a few in the region of the nasal
root and orbitals. Asymmetry was noted at over half of the bilateral landmarks.
The differences between the results from this sample and those obtained from
comparable databases contradict the hypothesis that population specificity
significantly influences facial soft tissue thickness.
PMID- 28417259
TI - Comparison between magnetic bead and qPCR library normalisation methods for
forensic MPS genotyping.
AB - Massively parallel sequencing (MPS) is fast approaching operational use in
forensic science, with the capability to analyse hundreds of DNA identity and DNA
intelligence markers in multiple samples simultaneously. The ForenSeqTM DNA
Signature Kit on MiSeq FGxTM (Illumina) workflow can provide profiles for
autosomal short tandem repeats (STRs), X chromosome and Y chromosome STRs,
identity single nucleotide polymorphisms (SNPs), biogeographical ancestry SNPs
and phenotype (eye and hair colour) SNPs from a sample. The library preparation
procedure involves a series of steps including target amplification, library
purification and library normalisation. This study highlights the comparison
between the manufacturer recommended magnetic bead normalisation and quantitative
polymerase chain reaction (qPCR) methods. Furthermore, two qPCR chemistries,
KAPA(r) (KAPA Biosystems) and NEBNext(r) (New England Bio Inc.), have also been
compared. The qPCR outperformed the bead normalisation method, while the
NEBNext(r) kit obtained higher genotype concordance than KAPA(r). The study also
established an MPS workflow that can be utilised in any operational forensic
laboratory.
PMID- 28417260
TI - Five-year survival analysis of surgically resected gastric cancer cases in Japan:
a retrospective analysis of more than 100,000 patients from the nationwide
registry of the Japanese Gastric Cancer Association (2001-2007).
AB - BACKGROUND: The aim of this retrospective study was to investigate the tumor
characteristics, surgical details, and survival distribution of surgically
resected cases of gastric cancer from the nationwide registry of the Japanese
Gastric Cancer Association. METHODS: Data from 118,367 patients with primary
gastric carcinoma who underwent resection between 2001 and 2007 were included in
the survival analyses. The 5-year survival rates were calculated for various
subsets of prognostic factors. RESULTS: The median age of the patients was 67
years. The proportions of patients with pathological stage (Japanese Gastric
Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%,
11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of
operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who
were treated by resection was 71.1%. The 5-year overall survival rates of
patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were
91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease
specific survival rates in the patients with pT1 (mucosa) disease after D1+
dissection of lymph node station no. 7 (D1 + alpha), D1+ dissection of lymph node
station nos. 7, 8, and 9 (D1+ beta), and D2 lymphadenectomy were 99.4%, 99.6%,
and 99.1% respectively. The 5-year disease-specific survival rates in the
patients with pT1 (submucosa) disease after D1 + alpha, D1 + beta, and D2
lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. CONCLUSION: Detailed
analyses of the data from more than 100,000 patients show the recent trends of
the outcomes of gastric cancer treatment in Japan and provide baseline
information for use by medical communities around world.
PMID- 28417261
TI - Neutrophil Infiltration and Matrix Metalloproteinase-9 in Lacunar Infarction.
AB - We use the modified pial vessel disruption rat model to elucidate the cellular
and molecular mechanisms of cavitation as it plays a role in lacunar infarction.
Here we discuss the similarities between the genesis of pulmonary cavitation in
various animal models and lacunar infarction in the cerebral cortex of rats. Both
pathological processes involve the creation of a cavity surrounded by fibroblasts
or reactive astrocytes. A crucial step in both, the lung and the cerebral cortex,
appears to be the migration of neutrophils across the endothelial barrier into
the parenchyma. In the lung and cerebral cortex this involves release of matrix
metalloproteinase-9 (MMP-9). Inside the parenchyma neutrophils continue to
release MMP-9. In both situations batimastat (BB-94) and minocycline reduce
release of MMP-9 and prevent cavitation. In the cerebral cortex MMP-9 release by
resident microglia plays an additional role. We therefore advance the hypothesis
that cavitation in both tissues is driven by MMP-9 originating from invading
neutrophils. Therapeutic intervention has to focus on these blood-borne intruder
cells and specific MMP actions. Batimastat and its derivatives (marimastat, BB
1101, mCGS-27023-A, ilomastat, GM6001, CTK8G1150) are already in clinical or
experimental use in humans for anti-cancer treatment, and these clinically
relevant drugs could be repurposed to act as anti-inflammatory to counter
neutrophil contribution to lung or cerebral cortex cavitation.
PMID- 28417262
TI - Melatonin Inhibits Neural Cell Apoptosis and Promotes Locomotor Recovery via
Activation of the Wnt/beta-Catenin Signaling Pathway After Spinal Cord Injury.
AB - The spinal cord is highly sensitive to spinal cord injury (SCI) by external
mechanical damage, resulting in irreversible neurological damage. Activation of
the Wnt/beta-catenin signaling pathway can effectively reduce apoptosis and
protect against SCI. Melatonin, an indoleamine originally isolated from bovine
pineal tissue, exerts neuroprotective effects after SCI through activation of the
Wnt/beta-catenin signaling pathway. In this study, we demonstrated that melatonin
exhibited neuroprotective effects on neuronal apoptosis and supported functional
recovery in a rat SCI model by activating the Wnt/beta-catenin signaling pathway.
We found that melatonin administration after SCI significantly upregulated the
expression of low-density lipoprotein receptor related protein 6 phosphorylation
(p-LRP-6), lymphoid enhancer factor-1 (LEF-1) and beta-catenin protein in the
spinal cord. Melatonin enhanced motor neuronal survival in the spinal cord
ventral horn and improved the locomotor functions of rats after SCI. Melatonin
administration after SCI also reduced the expression levels of Bax and cleaved
caspase-3 in the spinal cord and the proportion of terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive
cells, but increased the expression level of Bcl-2. These results suggest that
melatonin attenuated SCI by activating the Wnt/beta-catenin signaling pathway.
PMID- 28417263
TI - Rosuvastatin Attenuates High-Salt and Cholesterol Diet Induced Neuroinflammation
and Cognitive Impairment via Preventing Nuclear Factor KappaB Pathway.
AB - Recent attention is focused on the impact of diet on health and mental well
being. High-salt and cholesterol diet (HSCD) is known to be associated with
neuroinflammation which is the predominant factor for neurodegenerative disease
like Alzheimer disease (AD). In the present study, we examined the
neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against
HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated
that HSCD-induced cognitive impairment as determined by Morris water maze (MWM)
task. HSCD also activated nuclear factor kappaB (NF-kB) signaling pathway. The
cytokine response was measured using a cytometric bead-based assay quantified by
flow cytometry. Treatment with rosuvastatin decreased the production of nitric
oxide (NO), tumor necrosis factor alpha (TNF-alpha) and increased interleukin-10
(IL-10) in a dose-dependent manner. Our results also demonstrated that the
rosuvastatin modulates neuronal cell death by inhibiting the overexpression of NF
kB in the CA1 region of hippocampus. In addition, molecular docking study of
rosuvastatin indicated high affinity and tighter binding capacity for the active
site of the NF-kB. These results suggest that HSCD-triggered inflammatory
response and cognitive impairment may be associated with NF-kappaB signaling
pathway. Therefore, treatment with rosuvastatin could be a potential new
therapeutic strategy for sporadic dementia of AD.
PMID- 28417264
TI - Branched-Chain Amino Acids and Brain Metabolism.
AB - This review aims to provide a historical reference of branched-chain amino acid
(BCAA) metabolism and provide a link between peripheral and central nervous
system (CNS) metabolism of BCAAs. Leucine, isoleucine, and valine (Leu, Ile, and
Val) are unlike most other essential amino acids (AA), being transaminated
initially in extrahepatic tissues, and requiring interorgan or intertissue
shuttling for complete catabolism. Within the periphery, BCAAs are essential AAs
and are required for protein synthesis, and are key nitrogen donors in the form
of Glu, Gln, and Ala. Leucine is an activator of the mammalian (or mechanistic)
target of rapamycin, the master regulator of cell growth and proliferation. The
tissue distribution and activity of the catabolic enzymes in the peripheral
tissues as well as neurological effects in Maple Syrup Urine Disease (MSUD) show
the BCAAs have a role in the CNS. Interestingly, there are significant
differences between murine and human CNS enzyme distribution and activities. In
the CNS, BCAAs have roles in neurotransmitter synthesis, protein synthesis, food
intake regulation, and are implicated in diseases. MSUD is the most prolific
disease associated with BCAA metabolism, affecting the branched-chain alpha-keto
acid dehydrogenase complex (BCKDC). Mutations in the branched-chain
aminotransferases (BCATs) and the kinase for BCKDC also result in neurological
dysfunction. However, there are many questions of BCAA metabolism in the CNS (as
well as the periphery) that remain elusive. We discuss areas of BCAA and BCKA
metabolism that have yet to be researched adequately.
PMID- 28417265
TI - Advancing Drug Discovery and Development Using Molecular Imaging (ADDMI): an
Interest Group of the World Molecular Imaging Society and an Inaugural Session on
Positron Emission Tomography (PET).
AB - Multi-modality molecular imaging techniques have expanded the role of imaging
biomarkers in the pharmaceutical industry and are beginning to streamline the
drug discovery and development process. The World Molecular Imaging Society
(WMIS) serves as a forum for discussing innovative and exploratory multi-modal,
interdisciplinary molecular imaging research with a mission of bridging the gap
between pathology and in vivo imaging. To formalize the role of the WMIS in
pharmaceutical research efforts, members of the society have formed an interest
group entitled Advancing Drug Discovery and Development using Molecular Imaging
(ADDMI). The ADDMI interest group launched their efforts at the 2016 World
Molecular Imaging Congress by hosting a session of invited lectures on
translational positron emission tomography (PET) imaging in the central nervous
system. This article provides a synopsis of those lectures and frames the role of
translational imaging biomarker strategies in the drug discovery and development
process.
PMID- 28417266
TI - Guided longer pulses from a diagnostic ultrasound and intraclot microbubble
enhanced catheter-directed thrombolysis in vivo.
AB - The mechanism of ultrasound thrombolysis (UT) is generally attributed to
cavitation. The insufficiency of microbubbles (MB) to serve as cavitation nuclei
in the vessel-obstructing thrombi significantly reduces the effectiveness of UT.
Taking advantage of the widely performed catheter-directed therapy (CDT), in a
thrombo-embolized rabbit IVC model with a simultaneous catheter directed rt-PA
thrombolysis procedure, guided moderate mechanical index longer pulses from a
modified diagnostic ultrasound transducer, combined with an intraclot infusion of
MB, significantly accelerated the thrombolysis process. The higher thrombolysis
efficacy score and consistent elevated post-treatment plasma concentration level
of D-Dimer, a product of fibrinolysis, both indicated the superiority of CDT + UT
over CDT/UT alone. Pathologic examination of the treated occluded IVC segments
revealed an almost complete dissolution of the thrombi treated with CDT + UT.
There was no evidences of thrombo-embolism or local thrombus formation in the
cardiac-pulmonary vessels. Combined with intraclot infusion of MB, guided longer
pulse ultrasound from a diagnostic transducer is able to safely and significantly
improve a catheter-directed thrombolysis procedure. It thus has the potential to
achieve earlier clot removal, administration of a lower dosage of thrombolytic
agent and, consequently, a lower incidence of thrombolysis-related side effects.
PMID- 28417267
TI - Preemptive warfarin dose reduction after initiation of sulfamethoxazole
trimethoprim or metronidazole.
AB - To evaluate the utility of a preemptive warfarin dose reduction at the time of
initiation of either sulfamethoxazole-trimethoprim or metronidazole, a
retrospective chart review of patients who received an outpatient prescription
for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from
July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans
who had a warfarin dose reduction and those who did not within 120 h (5 days) of
antibiotic initiation. The primary outcome compared the pre-and post-antibiotic
International Normalized Ratio (INR) of patients in the intervention group
(warfarin dose reduction) with those in the control group (no intervention).
Secondary outcomes assessed incidence of thromboembolic and major bleeding events
within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine
patients had at least one follow-up appointment; 126 follow-up visits were
evaluated. There was a statistically significant difference for the change in
therapeutic INR at the first follow-up appointment (p = 0.029) for those patients
in the control group. On average, the patients in the intervention group required
fewer follow-up visits (p = 0.019). There were no statistically significant
differences for the overall rate of therapeutic INR values between groups, as
well as no instances of a thromboembolic or major bleeding events during the
follow-up period. Clinically significant differences were observed for patients
who received a preemptive warfarin dose reduction upon initiation of
sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention
group required fewer follow-up appointments and were more likely maintain a
therapeutic INR within the 30 days following the antibiotic course. Results of
this study will be presented the at Pharmacy and Therapeutics committee in an
effort to seek approval for policy development to initiate a local preemptive
warfarin dose adjustment as a standard of practice.
PMID- 28417268
TI - Sexual Behavior Among Persons With Cognitive Impairments.
AB - Although the cognitively impaired are frequently included in heterogeneous
studies of problematic sexual behavior, the epidemiology, etiology, and approach
to assessment and treatment of persons with dementia and intellectual disability
are distinct from those of the general population. The incidence of inappropriate
sexual behavior among the intellectually disabled is 15-33%; however, the nature
tends to be more socially inappropriate than with violative intent. Limited
sociosexual education is a large contributor, and better addressing this area
offers a target for prevention and treatment. A thorough clinical assessment of
problematic sexual behaviors in the cognitively impaired requires understanding
the patient's internal experience, which can be challenging. Assessment tools
validated for the general population have not been validated for this population.
Very few studies have assessed treatment approaches specifically among the
cognitively impaired; however, research does suggest utility in habilitative,
psychotherapeutic, and pharmacologic approaches which have been validated among
the general population.
PMID- 28417269
TI - Anxiety Disorders and Temperament-an Update Review.
AB - PURPOSE OF REVIEW: The review focused on associations between temperament
dimensions and clinical features in different anxiety disorders, likewise in
obsessive-compulsive disorder in clinical samples of adults. A literature search
was conducted in the Medline and PsycINFO databases covering the years 2010-2016.
A systematic review and grading of the level of evidence for an association
between temperament dimension scores and clinical features in each disorder were
performed. RECENT FINDINGS: Twenty papers reporting 18 different studies were
included. Five of the papers focused on panic disorder (PD), five on social
anxiety disorder (SAD), three on post-traumatic stress disorder (PTSD), one on
generalized anxiety disorder (GAD), three on obsessive-compulsive disorder (OCD),
and an additional three papers on several anxiety disorders. The review
consolidates the finding that trait anxiety, especially as assessed by
Cloninger's model or the five-factor model, is a phenomenon common to all anxiety
disorders and OCD. More follow-up studies including large samples are needed to
differentiate the dimensional profiles of trait anxiety in specific disorders.
PMID- 28417270
TI - Current Reports on Perinatal Intimate Partner Violence.
AB - PURPOSE OF REVIEW: The purpose of this study was to review the literature on
perinatal intimate partner violence, focusing on recent knowledge to guide mental
health professionals on the best approaches to identify and treat women exposed
to perinatal intimate partner violence. RECENT FINDINGS: Risk factors have been
broadened from individual victim and perpetrator factors to include relationship,
community, and societal factors which interact together. Better information is
now available on how to identify, document, and treat women exposed to violence
around the time of conception, pregnancy, and the postpartum period. Recent
information helps psychiatrists and other mental health professionals assist
women exposed to violence related to the perinatal period; however, further
research is needed to provide improved evidence for optimal interventions for
better patient outcomes.
PMID- 28417271
TI - Antimicrobial effects of Manuka honey on in vitro biofilm formation by
Clostridium difficile.
AB - Clostridium difficile is the cause of the nosocomial C. difficile infection
(CDI). The conventional antibiotics used in CDI therapy are often unsuccessful,
and recurrent infections may occur. Biofilm formation by C. difficile is
associated with chronic or recurrent infections; biofilms may contribute to
virulence and impaired antimicrobial efficacy. Manuka honey, derived from the
Manuka tree (Leptospermum scoparium), is known to exhibit antimicrobial
properties that are associated with its significant content of methylglyoxal, a
natural antibiotic. The aim of the present study was to determine the
antimicrobial effect of Manuka honey on clinical C. difficile strains belonging
to four prominent polymerase chain reaction (PCR) ribotypes (RTs) (RT017, RT023,
RT027 and RT046) and on their biofilm formation in vitro. Minimal inhibitory and
bactericidal concentrations (MICs and MBCs, respectively) were determined using
the broth dilution method. The biomass of the biofilm and the clearance of C.
difficile biofilms by Manuka honey were determined using the crystal violet
staining method. The MIC and MBC of Manuka honey for C. difficile strains were
equal at 6.25% (v/v). PCR RT027 strains produced more biofilm in vitro than the
other examined strains. Manuka honey effectively inhibited biofilm formation by
C. difficile strains of different PCR RTs.
PMID- 28417272
TI - Early administration of neuraminidase inhibitors in adult patients hospitalized
for influenza does not benefit survival: a retrospective cohort study.
AB - The administration of neuraminidase inhibitors (NAIs) within 2 days after the
onset of symptoms (early NAI therapy) has been shown to reduce mortality in adult
patients with severe influenza. However, there is no sufficiently solid evidence
supporting the effectiveness of early NAI therapy on mortality. We reviewed the
clinical data from 506 adult patients who were hospitalized for influenza between
March 2010 and March 2014, to investigate the impact of early NAI therapy on
mortality. Nearly one-third of the study patients were infected with influenza B
(influenza A, influenza B, and co-infection of both in 68.8%, 28.1%, and 3.2%,
respectively), and were diagnosed using the polymerase chain reaction (PCR)
method (33.6%). Less than half (233, 46.0%) had received early NAI therapy.
Patients with early NAI therapy were admitted to the hospital earlier, more
frequently infected with influenza A, and more frequently diagnosed using rapid
influenza detection tests compared to those without early NAI therapy. Although
patients without early NAI therapy presented with more serious clinical
manifestations, such as an initial symptom of dyspnea, pneumonia, and intensive
care unit admission, than those with early NAI therapy, the in-hospital mortality
of the former (2.9%, 8/273) did not differ from that of the latter (3.4%, 8/233)
(p = 0.75). We did not find a reduction in mortality associated with early NAI
therapy in adult patients hospitalized for influenza. Further clinical studies
including a large number of influenza B-infected patients with virus
identification using PCR methodology rather than viral culture may be required to
confirm the beneficial impact of early NAI therapy on mortality.
PMID- 28417273
TI - Maternal height and breast cancer risk: results from a study nested within the
EPIC-Greece cohort.
AB - The positive association of adult height with breast cancer (BC) risk has been
hypothesized to be partly accounted for by an association of this risk with
maternal height (operating in utero to modify hormone effects). In a case-control
study (271 BC patients and 791 controls) nested within the EPIC-Greece cohort, we
applied mediation analysis to calculate the direct and indirect (through the
woman's own height) effect of maternal height on BC risk. Per 5 cm increase in
maternal height and depending on its reference value: the indirect effect odds
ratio ranges from 1.02 to 1.07; the direct effect odds ratio from 1.06 to 1.11;
and the total (direct and indirect effects) from 1.08 to 1.19. The effect sizes
consistently increased for higher reference categories of maternal height, but
did not generally reach statistical significance, possibly due to the limited
sample size.
PMID- 28417274
TI - Dr. Rafael F. Capella, MD.
PMID- 28417275
TI - RNA silencing in the life cycle of soybean: multiple restriction systems and
spatiotemporal variation associated with plant architecture.
AB - The expression of transgenes introduced into a plant genome is sometimes
suppressed by RNA silencing. Although local and systemic spread of RNA silencing
have been studied, little is known about the mechanisms underlying spatial and
temporal variation in transgene silencing between individual plants or between
plants of different generations, which occurs seemingly stochastically. Here, we
analyzed the occurrence, spread, and transmission of RNA silencing of the green
fluorescent protein (GFP) gene over multiple generations of the progeny of a
single soybean transformant. Observation of GFP fluorescence in entire plants of
the T3-T5 generations indicated that the initiation and subsequent spread of GFP
silencing varied between individuals, although this GFP silencing most frequently
began in the primary leaves. In addition, GFP silencing could spread into the
outer layer of seed coat tissues but was hardly detectable in the embryos. These
results are consistent with the notion that transgene silencing involves its
reset during reproductive phase, initiation after germination, and systemic
spread in each generation. GFP silencing was absent in the pulvinus, suggesting
that its cortical cells inhibit cell-to-cell spread or induction of RNA
silencing. The extent of GFP silencing could differ between the stem and a
petiole or between petiolules, which have limited vascular bundles connecting
them and thus deter long-distant movement of silencing. Taken together, these
observations indicate that the initiation and/or spread of RNA silencing depend
on specific features of the architecture of the plant in addition to the
mechanisms that can be conserved in higher plants.
PMID- 28417276
TI - Assessing ASD in Adolescent Females with Anorexia Nervosa using Clinical and
Developmental Measures: a Preliminary Investigation.
AB - The aim of this study was to use standardised, clinical assessment tools to
explore the presence of Autism Spectrum Disorder (ASD) symptoms in a sample of
adolescent females with Anorexia Nervosa (AN), receiving either day-patient or
inpatient treatment for their eating disorder and to determine whether any such
symptoms were present during the early developmental period, a requirement for a
diagnosis of ASD. Using a cross-sectional design, 40 females aged between 12 and
18 were recruited from inpatient and day-patient eating disorder services. All
participants had a diagnosis of AN and were assessed for symptoms of ASD using
the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2). If participants
scored at or above clinical cut-off on the ADOS-2, their parents were asked to
complete the Developmental, Dimensional and Diagnostic Interview, short version
(3Di-sv). Of the 40 participants assessed, 21 scored above cut-off on the ADOS-2.
When developmental history was obtained, only four participants scored above cut
off on all sub-scales of the 3Di-sv, thus meeting full research criteria for ASD.
This study suggests that 10% of adolescents with AN from inpatient or day-patient
settings may have diagnosable ASD, while a further 40% may show symptoms of ASD,
which may arise from the ill-state of AN or are not supported by parental report.
PMID- 28417277
TI - Clandestine charisma of the charm needles: a radiologist's challenge.
AB - A 94-year-old Korean woman was seen in the Emergency Department after a fall. CT
examination of the maxillofacial region found multiple small linear metallic
densities in the subcutaneous soft tissues of the face. The appearance of these
densities was unchanged when compared to a study performed 2 years prior;
however, the imaging interpretations of these densities were markedly different.
Additional imaging during the course of her hospital stay demonstrated numerous
similar densities in the breasts, abdomen, hips, and legs-finally diagnosed as
"charm needles." Although common practice in Southeast Asia, with ever increasing
globalization, these needles, or "susuks," are being seen with greater frequency
in North America. Here, we review the imaging appearance of a bizarre case of
these charm needles so as to raise awareness of this potential diagnostic
challenge and help the radiologist avoid confusion when interpreting images.
PMID- 28417278
TI - Comment to: "No enterocutaneous fistula development in a cohort of 695 patients
after incisional hernia repair using intraperitoneal uncoated polypropylene mesh"
by Brandi, C.D., Roche, S., Bertone, S. et al. Hernia (2017) 21: 101.
PMID- 28417280
TI - New isolation technique for enteroatmospheric fistula in Bjorck 4 open abdomen.
PMID- 28417279
TI - Tackers versus glue mesh fixation: an objective assessment of postoperative acute
and chronic pain using inflammatory markers.
AB - PURPOSE: Laparoscopic hernioplasty has become a popular choice for inguinal
hernia repair since its advent in 1990s. Postoperative pain is an undesirable
clinical outcome impairing daily activity of 22.5% of patients. The aim of this
study is to evaluate postoperative acute and chronic pain via inflammatory
markers as an objective assessment following tacks or glue mesh fixation in TEP
repair. METHODS: Sixty-six (66) patients with unilateral uncomplicated inguinal
hernia were randomized into 34 patients in the tacker and 32 patients in
cyanoacrylate glue mesh fixation in TEP repair. The extent of surgical trauma was
evaluated by measuring inflammatory markers of C-reactive protein, white blood
cell count at 48 h, and ESR at 3 months postoperatively. Postoperative acute and
chronic pain was assessed by recording the visual analogue scale scores and
surgical complications were recorded over 3 months of the study period. RESULTS:
The median CRP and WBC levels at postoperative 48 h in both groups raised
significantly from the baseline values (p < 0.05), however, did not differ
significantly between the two study groups at 48 h (p > 0.05). The median ESR
level increased significantly at 3 months postoperatively from baseline in the
glue mesh fixation group only (p < 0.05), however, did not differ significantly
between the two study groups (p > 0.05). There was no significant difference for
VAS scores at all timelines between the tacker and glue mesh fixation group (p >
0.05). CONCLUSION: Cyanoacrylate glue mesh fixation technique as an alternative
method to mechanical fixation in TEP repair is comparable to tacker and can be
considered to be safe and feasible.
PMID- 28417281
TI - Historical record of anthropogenic polycyclic aromatic hydrocarbons in a lake
sediment from the southern Tibetan Plateau.
AB - High-altitude lake sediments can be used as natural archives to reconstruct the
history of pollutants. In this work, the temporal distribution of polycyclic
aromatic hydrocarbons (PAHs) was determined in a sediment core collected from the
southern Tibetan Plateau (TP), which was dated by using the 210Pb dating method
and validated with the 137Cs fallout peak. The concentrations of the
anthropogenic PAHs (Sigma8PAH) in the sediment core ranged from 0.83 to 12 ng/g
dw, and the fluxes of the Sigma8PAH were in the range of 2.1-27 g/cm2/year. The
temporal variations in the concentration and input flux of anthropogenic PAHs
were low with little variability before the 1950s, and then gradually increased
from the 1950s to the 1980s, and an accelerated increase was observed after the
early 1980s. The content of total organic carbon played an insignificant role in
affecting the time trends of PAHs in the sediment core. Diagnostic concentration
fractions of PAH components indicate PAHs in the lake sediment of the southern TP
which are mainly from biomass burning and/or from long-range atmospheric
transport.
PMID- 28417282
TI - Coastal modification of a scene employing multispectral images and vector
operators.
AB - Changes in sea level, wind patterns, sea current patterns, and tide patterns have
produced morphologic transformations in the coastline area of Tamaulipas Sate in
North East Mexico. Such changes generated a modification of the coastline and
variations of the texture-relief and texture of the continental area of
Tamaulipas. Two high-resolution multispectral satellite Satellites Pour
l'Observation de la Terre images were employed to quantify the morphologic change
of such continental area. The images cover a time span close to 10 years. A
variant of the principal component analysis was used to delineate the
modification of the land-water line. To quantify changes in texture-relief and
texture, principal component analysis was applied to the multispectral images.
The first principal components of each image were modeled as a discrete
bidimensional vector field. The divergence and Laplacian vector operators were
applied to the discrete vector field. The divergence provided the change of
texture, while the Laplacian produced the change of texture-relief in the area of
study.
PMID- 28417283
TI - Bis-anthracycline WP760 abrogates melanoma cell growth by transcription
inhibition, p53 activation and IGF1R downregulation.
AB - Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active
against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to
DNA intercalation, interference with topoisomerase activity, and induction of
double-stranded DNA breaks. Since modification of anthracyclines can profoundly
affect their pharmacological properties we attempted to elucidate the mechanism
of action, and identify possible molecular targets, of bis-anthracycline WP760
which previously demonstrated anti-melanoma activity at low nanomolar
concentrations. We studied the effect of WP760 on several human melanoma cell
lines derived from tumors in various development stages and having different
genetic backgrounds. WP760 inhibited cell proliferation (IC50 = 1-99 nM),
impaired clonogenic cell survival (100 nM), and inhibited spheroid growth (>=300
nM). WP760 did not induce double-stranded DNA breaks but strongly inhibited
global transcription. Moreover, WP760 caused nucleolar stress and led to
activation of the p53 pathway. PCR array analysis showed that WP760 suppressed
transcription of ten genes (ABCC1, MTOR, IGF1R, EGFR, GRB2, PRKCA, PRKCE, HDAC4,
TXNRD1, AKT1) associated with, inter alia, cytoprotective mechanisms initiated in
cancer cells during chemotherapy. Furthermore, WP760 downregulated IGF1R and
upregulated PLK2 expression in most of the tested melanoma cell lines. These
results suggest that WP760 exerts anti-melanoma activity by targeting global
transcription and activation of the p53 pathway and could become suitable as an
effective therapeutic agent.
PMID- 28417284
TI - A phase I dose-escalation study of the safety and pharmacokinetics of a tablet
formulation of voxtalisib, a phosphoinositide 3-kinase inhibitor, in patients
with solid tumors.
AB - Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in
capsule formulation in patients with solid tumors. This Phase I study assessed
safety and pharmacokinetics of voxtalisib administered as immediate-release
tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose
escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food
effect and tumor response were evaluated. Results Thirty-two patients received
voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients
received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two
28-day cycles. Dose-limiting toxicities (DLTs) were Grade 3 fatigue (two patients
at 70 mg QD, one patient at 40 mg BID) and Grade 3 rash (two patients at 50 mg
BID). The maximum tolerated dose (MTD) was 60 mg for QD and 40 mg for BID
regimens. Common treatment-emergent AEs were diarrhea (41%), nausea (37%) and
fatigue (33%). Voxtalisib appeared to follow linear PK, with a general increase
in plasma exposure with dose and no significant accumulation. Administration with
food caused a slight decrease in exposure; however, given the high variability
observed in the exposure parameters, this should be interpreted with caution.
Best response was stable disease in 29% and 50% of patients (QD and BID regimens,
respectively). Conclusions The safety profile of voxtalisib tablets at the MTD in
patients with solid tumors was consistent with that observed with voxtalisib
capsules. Given the limited activity observed across multiple clinical trials, no
further trials of voxtalisib are planned.
PMID- 28417285
TI - Alcohol and thiamine deficiency trigger differential mitochondrial transition
pore opening mediating cellular death.
AB - Accumulating evidence has shown that binge-type alcohol intake in mothers
interferes with thiamine deficiency (TD) to promote the fetal alcohol syndrome
(FAS). Developmental alcohol or TD exposures act either synergistically or
separately to reproduce FAS features e.g. intrauterine growth retardation and
related microcephaly characterized by extensive cellular death induced by one
another neurotoxicant. However molecular and cellular mechanisms underlying
apoptosis in both alcohol and TD toxicities are unknown. The current review
addresses mechanisms of apoptosis underlying alcohol and TD toxicities for
further understanding FAS pathology. This study indicates two different
mitochondria pathways regulating cellular death: The first mechanism may engage
alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT
pore-dependent apoptosis; following the second mechanism, TD activates CyP-D
translocation from mitochondrial matrix towards the mitochondrial inner membrane
to form MPT pore-dependent necrosis. These studies shed light upon molecular and
cellular mechanisms underlying apoptosis and necrosis in developemental brain
disorders related to alcohol and thiamine deficiency, in hopes of developing new
therapeutic strategies for FAS medication.
PMID- 28417286
TI - Retraction Note to: Advanced oxidation protein products induce chondrocyte death
through a redox-dependent, poly(ADP-ribose) polymerase-1-mediated pathway.
PMID- 28417287
TI - Predictors of arrhythmia recurrence after balloon cryoablation of atrial
fibrillation: the value of CAAP-AF risk scoring system.
AB - PURPOSE: In the present study, we aimed to test the value of CAAP-AF score for
prediction of atrial fibrillation (AF) recurrence at follow-up in a group of our
patients treated by balloon cryoablation. METHODS: A total of 283 symptomatic
drug-refractory AF patients [261 (92%) with paroxysmal AF] who underwent
pulmonary vein isolation (PVI) with second-generation cryoballoon between April
2012 and October 2016 were included. The CAAP-AF score was calculated for every
patient. RESULTS: A total of 283 patients [68 female (20%), mean age 59.8 +/-
11.4 years] were included in the present analysis. Eighty-nine patients (31%) had
hypertension and 13 (4%) had coronary artery disease. The mean left atrial
diameter and left ventricular ejection fraction were 40.6 +/- 7.0 mm and 60.0 +/-
9.1%, respectively. The mean CHA2DS2-VASc score was 1.2 +/- 1.1, and mean number
of prior failed antiarrhythmic drugs was 1.4 +/- 0.8. At 18 +/- 6 months follow
up, 25 patients (8.87%) developed AF recurrence. The recurrence rate was as
follows: 3.17% (score 0-3), 8.47% (score 4), 16.28% (score 5), 6.67% (score 6),
23.08% (score 7), and 36.36% (score >=8). The recurrence rate was 4.86% at a
score <5 and 16.49% at a value >=5; a score cutoff >=5 predicted AF recurrence
with a sensitivity 64% and specificity 68%. CONCLUSIONS: The present analysis
suggests the usefulness of CAAP-AF scoring system, with its simple and easily
obtained six clinical variables, to predict AF recurrence after PVI by means of
second-generation cryoballoon. A score value >=5 predicted AF recurrence with a
sensitivity 64% and specificity 68%.
PMID- 28417288
TI - Troponin T elevation after permanent pacemaker implantation.
AB - PURPOSE: The objective of the study is to study the incidence, significance, and
factors associated with cardiac troponin T (CTNT) elevation after pacemaker
implantation. METHODS: Three hundred seventy-four patients (104 single-chamber
pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization
therapy/cardiac resynchronization therapy defibrillator) who had normal levels of
CTNT at baseline and underwent implantation of a permanent pacemaker system were
included in this study. Serum levels of CTNT were measured at baseline, 6 and 24
h after the implantation procedure. RESULTS: The median of CTNT levels increased
from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the
procedure, respectively (all p < 0.0001). Elevated CTNT levels were noted in 208
patients (55.6%) at 6 h after the implantation, among which 29 patients (7.8%)
had CTNT levels exceeding the range of minimal myocardial damage (>0.09 ng/mL).
After 1-year follow-up, the incidence of complications including dislodgement of
the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and
cardiac outcomes including hospitalization of heart failure, coronary artery
disease, arrhythmia, and cardiovascular mortality was not significantly different
between the normal and elevated CTNT groups at 6 h after the procedure. By
logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide
(NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated
glomerular filtration rate (eGFR), and fluoroscopy time were independently
associated with CTNT elevation after adjusted for age, pacemaker types, right
ventricle lead location (RVA or RVOT), heart function, and left ventricular end
systolic dimension. CONCLUSIONS: Pacemaker implantation was found to be
accompanied with CTNT elevation in 55.6% of the patients at 6 h after the
procedure, and its kinetics were fast, which might not be related to the
complications and adverse cardiac outcomes within 1 year of follow-up. Moreover,
gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be
independent predictors of CTNT elevation.
PMID- 28417289
TI - Reporting the margin in pancreaticoduodenectomies: R0 versus R1.
AB - AIM: This study was conducted to analyze the changes in margin positivity in
pancreaticoduodenectomies, on using a standardized protocol, which bread loafs
the pancreas and duodenum in the axial plane for adenocarcinomas arising in the
pancreatic head, ampulla, terminal common bile duct (CBD), and duodenum, and then
to assess whether these tumor subsets involve the margins in different ways.
METHODS: The analysis was performed on 70 consecutive specimens, the pre-protocol
specimens serving as the control group. RESULTS AND CONCLUSIONS: Tumors
originating from the pancreatic head, ampulla, terminal CBD, and duodenum showed
a consistent increase in their R1 incidence, post-protocol. Ampullary tumors
showed the greatest upward change in R1 positivity. The highest incidence of
margin positivity was seen in pancreatic head adenocarcinomas (80%), then distal
CBD tumors (60%), and finally the ampullary tumors (39%). In pancreatic head
adenocarcinomas, R1 increased from 55% to 80%, distal CBD from 50% to 60%, and
ampullary from 17% to 39%. Duodenal adenocarcinomas had no R1 in both pre- and
post-protocol groups. The tumors also had different patterns of margin
involvement. Ampullary tumors involved only the posterior margin, pancreatic
adenocarcinomas involved the superior mesenteric vein (SMV) groove more often
than the posterior margin, and distal CBD tumors involved the posterior margin
and SMV groove equally. The size of the tumor made a significant difference in
pancreatic head carcinomas with tumor size less than or equal to 2 cm, showing an
R1 incidence of 38%, while those above 2 cm had an R1 incidence of 68%.
PMID- 28417290
TI - Unilateral external fixator in the treatment of humeral shaft fractures: results
of a single center retrospective study.
AB - BACKGROUND: The aim of our work is to evaluate and critically analyze long-term
clinical and radiological data of a new unilateral external fixator (MIKAI KIT
FEP(c)-Mikai S.p.A, Genoa, Italy), in the treatment of humeral shaft fractures.
MATERIALS AND METHODS: We reviewed 47 patients affected by humeral fractures that
underwent surgery from July 2010 to March 2016 with unilateral external fixator.
Demographic characteristics of the patients were recorded, which included age,
sex and baseline comorbidities and mechanism of injury. Surgical data such as
time of surgery and time of fixation according to AO-type of fracture, clinical
objective and subjective outcomes were collected. RESULTS: The mean follow-up was
50.4 months (range 12-74). The patients' average age was 41.8 years (range 14
92). Mean surgical time was 66.8 (+/-37.7 min); and mean time of fixation was 4.5
(+/-1.7 months). We observed five delayed union (10.6%); one refracture (2.1%);
and one case of non-union (2.1%) who underwent a revision surgery with nailing.
No malunion was detected. Average quick-DASH was 11.7 (+/-14.8). The mean
Constant Score at final follow-up was 81.5 (+/-14). 95.8% of patients were
satisfied of our treatment. According to SF-12 scores, we observed 44 (93.6%)
good results and 3 (6.4%) poor results. CONCLUSION: We suggest the use of MIKAI
KIT FEP(c) as a feasible option in the treatment of humeral shaft fractures. We
reported optimal clinical and radiological outcomes at long-term follow-up. We
advocate more powerful evidence to validate this new possible approach.
PMID- 28417291
TI - Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from
Neurophysiology to Neuroimaging.
AB - PURPOSE OF REVIEW: Surprises are important sources of learning. Cognitive
scientists often refer to surprises as "reward prediction errors," a parameter
that captures discrepancies between expectations and actual outcomes. Here, we
integrate neurophysiological and functional magnetic resonance imaging (fMRI)
results addressing the processing of reward prediction errors and how they might
be altered in drug addiction and Parkinson's disease. RECENT FINDINGS: By
increasing phasic dopamine responses, drugs might accentuate prediction error
signals, causing increases in fMRI activity in mesolimbic areas in response to
drugs. Chronic substance dependence, by contrast, has been linked with
compromised dopaminergic function, which might be associated with blunted fMRI
responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's
disease, dopamine replacement therapies seem to induce impairments in learning
from negative outcomes. The present review provides a holistic overview of reward
prediction errors across different pathologies and might inform future clinical
strategies targeting impulsive/compulsive disorders.
PMID- 28417292
TI - Probiotic Strawberry Yogurts: Microbiological, Chemical and Sensory Properties.
AB - This study was performed to determine the viability of Lactobacillus acidophilus
and Bifidobacterium bifidum in yogurt made with strawberry marmalade (SM) and to
examine the quality properties of probiotic yogurt. Acidity, pH, bacterial counts
and sensory analysis of the yogurt samples were investigated on days 1, 3, 5, 7,
10 and 14 during storage at 4 degrees C. The survival rate of L. acidophilus was
greater than that of B. bifidum. The viability of L. acidophilus decreased during
the storage period, but B. bifidum numbers remained stable during the storage
period. The highest L. acidophilus count (7.20 log cfu/g) was found in L.
acidophilus + B. bifidum SM yogurt on day 1. The highest B. bifidum count (6.13
log cfu/g) was detected in yogurt containing L. acidophilus + B. bifidum SM
yogurt on day 7. Yeast and mould counts of all yogurts increased during the
storage period. Coliform bacteria and Staphylococcus aureus were not detected in
the yogurt samples. The highest overall acceptance sensory score was observed in
yogurts containing L. acidophilus. Considering the sensory and probiotic
characteristics of all yogurt samples, this study suggested that strawberry
yogurt with a suitable 5-7 day storage period can be produced with single L.
acidophilus addition or single B. bifidum addition.
PMID- 28417293
TI - Improvement of Geographic Disparities: Amelioration or Displacement?
AB - Progression of geographic disparities in social determinants of health is a
global concern. Using an Urban Health Index (UHI) approach, we proposed a
framework of examining the change of geographic disparities in social
determinants in small areas. Using the City of Atlanta in Georgia (USA) as a case
study, we standardized six census-based social determinant indicators in 2000 and
in 2010, respectively, and calculated their geometric mean to assign each census
tract a UHI value for 2000 and for 2010. We then evaluated the temporal change of
the UHIs in relation to the demographic changes using spatial and statistical
methods. We found that Atlanta experienced an improvement in social determinant
status and a reduction of disparities in the 10 years. The areas that experienced
improvement, however, underwent demographic changes as well. This analysis
provides support for displacement, rather than improvement, as the underlying
factor for apparent change in geographic disparities. Findings suggest the
importance of local evaluation for future policies to reduce disparities in
cities.
PMID- 28417294
TI - High trait shame undermines the protective effects of prevalence knowledge on
state shame following HPV/CIN diagnosis in women.
AB - Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia
(CIN), are common yet poorly understood physical conditions. The diagnosis of HPV
often elicits shame and guilt, which in turn may undermine psychological and
physical health. The current study compared shame and guilt responses to
diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with
Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or
EBV/IM completed measures of shame- and guilt-proneness, shame and guilt
following diagnosis, and disease knowledge including prevalence estimates (HPV
and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related
shame and guilt. Estimates of high prevalence interacted with diagnosis and shame
proneness to predict diagnosis-related shame. Simple slope analyses indicated
that in women with HPV/CIN reporting low-to-average shame-proneness, high
prevalence estimates reduced diagnosis-related shame; however, women high in
shame-proneness experienced high diagnosis-related shame regardless of more
accurate prevalence estimates. Women high in shame-proneness appear to be
particularly vulnerable to HPV-related shame even when they are aware that it is
very common.
PMID- 28417295
TI - Drug-induced pulmonary arterial hypertension: a review.
AB - Pulmonary arterial hypertension (PAH) is a subgroup of PH patients characterized
hemodynamically by the presence of pre-capillary PH, defined by a pulmonary
artery wedge pressure (PAWP) <=15 mmHg and a PVR >3 Wood units (WU) in the
absence of other causes of pre-capillary PH. According to the current
classification, PAH can be associated with exposure to certain drugs or toxins
such as anorectic agents, amphetamines, or selective serotonin reuptake
inhibitors. With the improvement in awareness and recognition of the drug-induced
PAH, it allowed the identification of additional drugs associated with an
increased risk for the development of PAH. The supposed mechanism is an increase
in the serotonin levels or activation of serotonin receptors that has been
demonstrated to act as a growth factor for the pulmonary artery smooth muscle
cells and cause progressive obliteration of the pulmonary vasculature. PAH
remains a rare complication of several drugs, suggesting possible individual
susceptibility, and further studies are needed to identify patients at risk of
drug-induced PAH.
PMID- 28417296
TI - DPP4 inhibitors and cardiovascular outcomes: safety on heart failure.
AB - Diabetes is an important risk factor for cardiovascular disease. However,
clinical data suggests intensive glycemic control significantly increase rather
than decrease cardiovascular mortality, which is largely due to the fact that a
majority of oral anti-diabetic drugs have adverse cardiovascular effect. There
are several large-scale clinical trials evaluating the cardiovascular safety of
DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been
recently completed. They were proven to be safe with regard to cardiovascular
outcomes. However, concerns on the safety of heart failure have been raised as
the SAVOR-TIMI 53 trial reported a 27% increase in the risk for heart failure
hospitalization in diabetic patients treated with DPP4 inhibitor saxagliptin. In
this review, we will discuss recent advances in the heart failure effects of DPP4
inhibition and GLP-1 agonism.
PMID- 28417298
TI - Disseminated Mycobacterium malmoense and Salmonella Infections Associated with a
Novel Variant in NFKBIA.
PMID- 28417297
TI - Regulation of the glucose supply from capillary to tissue examined by developing
a capillary model.
AB - A new glucose transport model relying upon diffusion and convection across the
capillary membrane was developed, and supplemented with tissue space and lymph
flow. The rate of glucose utilization (J util) in the tissue space was described
as a saturation function of glucose concentration in the interstitial fluid (C
glu,isf), and was varied by applying a scaling factor f to J max. With f = 0, the
glucose diffusion ceased within ~20 min. While, with increasing f, the diffusion
was accelerated through a decrease in C glu,isf, but the convective flux remained
close to resting level. When the glucose supplying capacity of the capillary was
measured with a criterion of J util /J max = 0.5, the capacity increased in
proportion to the number of perfused capillaries. A consistent profile of
declining C glu,isf along the capillary axis was observed at the criterion of 0.5
irrespective of the capillary number. Increasing blood flow scarcely improved the
supplying capacity.
PMID- 28417299
TI - Negative prognostic effect of low nuclear GLI1 expression in glioblastomas.
AB - The hedgehog signaling plays supportive roles in various aspects of
tumorigenesis. Increased expression of the key component, GLI1, has been shown to
correlate with poor prognosis in many types of cancers. We aimed to investigate
the effect of GLI1 expression in glioblastoma focusing on the nuclear
localization. Immunohistochemistry for GLI1, GLI2, PTCH1, SMO, and SHH were done
in 140 glioblastoma tissues, and the staining was graded. For GLI1, nuclear and
cytoplasmic expression was separately assessed. No significant correlation was
found between clinicopathologic parameters and expression grades of the five
proteins. Low nuclear GLI1 expression was associated with a worse progression
free survival while overall survival was not significantly affected. In contrast,
cytoplasmic GLI1 expression did not have a prognostic effect. PTCH1 expression
correlated with nuclear GLI1 expression without exerting a significant prognostic
effect. Analysis of the TCGA-glioblastoma dataset revealed that low GLI1 mRNA
level also correlated with a poor prognosis for both overall and progression-free
survival. The adverse effect of low nuclear GLI1 expression in glioblastomas is
in contrast with the negative prognostic effect of high GLI1 expression reported
in non-cranial malignancies. The relative impact of hedgehog signaling among
other oncogenic pathways in the brain may be responsible for the difference. The
different implication of GLI1 expression in glioblastomas needs to be considered
in studies of hedgehog signaling-targeted therapy.
PMID- 28417301
TI - Overview of Coronary Heart Disease Risk Initiatives in South Asia.
AB - PURPOSE OF REVIEW: Cardiovascular disease (CVD) is now the leading cause of
morbidity and mortality worldwide. Industrialization and economic growth have led
to an unprecedented increment in the burden of CVD and their risk factors in less
industrialized regions of the world. While there are abundant data on CVD and
their risk factors from longitudinal cohort studies done in the West, good
quality data from South Asia are lacking. RECENT FINDINGS: Several multi
institutional, observational, prospective registries, and epidemiologic cohorts
in South Asia have been established to systematically evaluate the burden of CVD
and their risk factors. The PINNACLE (Practice Innovation and Clinical
Excellence) India Quality Improvement Program (PIQIP), the Kerala Acute Coronary
Syndrome (ACS), and Trivandrum Heart Failure registries have focused on secondary
prevention of CVD and performance measurement in both outpatient and inpatient
settings, respectively. The Prospective Urban and Rural Epidemiology (PURE),
Centre for Cardiometabolic Risk Reduction in South Asia (CARRS), and other
epidemiologic and genetic studies have focused on primary prevention of CVD and
evaluated variables such as environment, smoking, physical activity, health
systems, food and nutrition policy, dietary consumption patterns, socioeconomic
factors, and healthy neighborhoods. The international cardiovascular community
has been responsive to a burgeoning cardiovascular disease burden in South Asia.
Several collaborations have formed between the West (North America in particular)
and South Asia to catalyze evidence-based and data-driven changes in the federal
health policy in this part of the world to promote cardiovascular health and
mitigate cardiovascular risk.
PMID- 28417300
TI - A live gI/gE-deleted pseudorabies virus (PRV) protects weaned piglets against
lethal variant PRV challenge.
AB - Emerging pseudorabies virus (PRV) variant has led to frequent outbreaks of PRV
infection among Bartha-K61-vaccinated swine population in Chinese swine farms and
caused high mortality in pigs of all age since late 2011. Here, we generated a
gE/gI-deleted PRV (rPRVXJ-delgI/gE-EGFP) based on PRV variant strain (PRV-XJ)
through homologous DNA recombination. Compared to parental strain, rPRVXJ
delgI/gE-EGFP showed similar growth kinetics in vitro. Its safety and
immunogenicity were evaluated in weaned piglets. Our results showed that piglets
immunized with rPRVXJ-delgI/gE-EGFP did not exhibit any clinical symptoms, and a
high level of gB-specific antibody was detected. After lethal challenge with
variant PRV (PRV-FJ strain), all vaccinated piglets survived without showing any
clinical symptoms except slight fever within 7 days post-challenge. In
unvaccinated piglets, typical clinical symptoms of pseudorabies were observed,
and the piglets were all died at 5 days post-challenge. These results indicated
that a live rPRVXJ-delgI/gE-EGFP vaccine could be a maker vaccine candidate to
control the currently epidemic pseudorabies in China.
PMID- 28417303
TI - Paediatric in-patient prescribing errors in Malaysia: a cross-sectional
multicentre study.
AB - Background There is a lack of large comprehensive studies in developing countries
on paediatric in-patient prescribing errors in different settings. Objectives To
determine the characteristics of in-patient prescribing errors among paediatric
patients. Setting General paediatric wards, neonatal intensive care units and
paediatric intensive care units in government hospitals in Malaysia. Methods This
is a cross-sectional multicentre study involving 17 participating hospitals. Drug
charts were reviewed in each ward to identify the prescribing errors. All
prescribing errors identified were further assessed for their potential clinical
consequences, likely causes and contributing factors. Main outcome measures
Incidence, types, potential clinical consequences, causes and contributing
factors of the prescribing errors. Results The overall prescribing error rate was
9.2% out of 17,889 prescribed medications. There was no significant difference in
the prescribing error rates between different types of hospitals or wards. The
use of electronic prescribing had a higher prescribing error rate than manual
prescribing (16.9 vs 8.2%, p < 0.05). Twenty eight (1.7%) prescribing errors were
deemed to have serious potential clinical consequences and 2 (0.1%) were judged
to be potentially fatal. Most of the errors were attributed to human factors,
i.e. performance or knowledge deficit. The most common contributing factors were
due to lack of supervision or of knowledge. Conclusions Although electronic
prescribing may potentially improve safety, it may conversely cause prescribing
errors due to suboptimal interfaces and cumbersome work processes. Junior doctors
need specific training in paediatric prescribing and close supervision to reduce
prescribing errors in paediatric in-patients.
PMID- 28417304
TI - 2016 ASMS Workshop Review: Next Generation LC/MS: Critical Insights and Future
Perspectives.
PMID- 28417306
TI - A Focus Honoring R. Graham Cooks' Election to the National Academy of Sciences.
PMID- 28417305
TI - Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters
via Photochemical Reaction and Tandem Mass Spectrometry.
AB - Mass spectrometry analysis of cholesteryl esters (CEs) faces several challenges,
with one of them being the determination of the carbon-carbon double bond (C=C)
locations within unsaturated fatty acyl chains. Patern?-Buchi (PB) reaction, a
photochemical reaction based on the addition of acetone to C=C, is capable of C=C
location determination when coupled with tandem mass spectrometry (MS/MS). In
this study, the PB reaction conditions were tailored for CEs and subsequent
nanoelectrospray ionization (nanoESI). A solvent system containing
acetone/methanol/dichloromethane/water (40/30/20/10, volume ratios) and 100 MUM
LiOH was determined to be optimal, resulting in reasonable PB reaction yield
(~30%) and good ionization efficiency (forming lithium adduct of CEs). Collision
induced dissociation (CID) of the PB reaction products produced characteristic
fragment ions of CE together with those modified by the PB reactions, such as
lithiated fatty acyl ([FA + Li]+) and its PB product ([FA - PB + Li]+). MS3 CID
of [FA - PB + Li]+ led to abundant C=C diagnostic ion formation, which was used
for C=C location determination and isomer quantitation. A PB-MS3 CID approach was
developed and applied for CE analysis from human plasma. A series of unsaturated
CEs was identified with specific C=C locations within fatty acyl chains. Absolute
quantitation for each CE species was achieved including coexisting C=C location
isomers, such as Delta9 and Delta11 isomers of CE 18:1 and omega-6 and omega-3
isomers of CE 18:3. These results show that PB-MS/MS is useful in uncovering
structural diversity of CEs due to unsaturation in fatty acyls, which is often
undetected from current lipid analysis approach. Graphical Abstract ?.
PMID- 28417307
TI - Investigating Differences in Gas-Phase Conformations of 25-Hydroxyvitamin D3
Sodiated Epimers using Ion Mobility-Mass Spectrometry and Theoretical Modeling.
AB - Drift tube ion mobility coupled with mass spectrometry was used to investigate
the gas-phase structure of 25-hydroxyvitamin D3 (25OHD3) and D2 (25OHD2) epimers,
and to evaluate its potential in rapid separation of these compounds.
Experimental results revealed two distinct drift species for the 25OHD3 sodiated
monomer, whereas only one of these conformations was observed for its epimer
(epi25OHD3). The unique species allowed 25OHD3 to be readily distinguished, and
the same pattern was observed for 25OHD2 epimers. Theoretical modeling of 25OHD3
epimers identified energetically stable gas-phase structures, indicating that
both compounds may adopt a compact "closed" conformation, but that 25OHD3 may
also adopt a slightly less energetically favorable "open" conformation that is
not accessible to its epimer. Calculated theoretical collision cross-sections for
these structures agreed with experimental results to <2%. Experimentation
indicated that additional energy in the ESI source (i.e., increased temperature,
spray voltage) affected the ratio of 25OHD3 conformations, with the less
energetically favorable "open" conformation increasing in relative intensity.
Finally, LC-IM-MS results yielded linear quantitation of 25OHD3, in the presence
of the epimer interference, at biologically relevant concentrations. This study
demonstrates that ion mobility can be used in tandem with theoretical modeling to
determine structural differences that contribute to drift separation. These
separation capabilities provide potential for rapid (<60 ms) identification of
25OHD3 and 25OHD2 in mixtures with their epimers. Graphical Abstract ?.
PMID- 28417308
TI - Treatment of menstrual migraine; multidisciplinary or mono-disciplinary approach.
AB - BACKGROUND: The aim of this study was to compare a multidisciplinary approach of
menstrual (related) migraine, combining the neurological and gynaecological
consultation, to a mono-disciplinary approach involving neurological treatment.
There is a clear relationship between the menstruation cycle and the occurrence
of migraine (menstrual migraine). Nowadays the treatment of menstrual (related)
migraine is performed by a neurologist. A treatment with attention to hormonal
treatment seems more convenient. METHODS: This retrospective study was performed
in a cohort using data of 88 women with menstrual (related) migraine who visited
the menstrual migraine clinic between 2012 and 2014 (intervention group). The
results were compared to a historical control group, which consisted of women
with menstrual (related) migraine who were treated before 2012 and received a
mono-disciplinary approach. RESULTS: In the intervention group the Headache
Impact (HIT) score significantly improved (65 to 59 points). The mean headache
days per month declined significantly (from 6 to 3.83 days) and these women
needed less use of pain medication. In the control group the decline in HIT score
was less striking (65 to 63.5 points) and the mean headache days per month
increased (6 to 6,5 days). It appeared that 20 out of 27 patients in the control
group required a gynaecological consultation in course of time. CONCLUSION: A
multidisicplinary treatment of women with menstrual (related) migraine gives
better results compared to a mono-disciplinary approach. These results should be
interpreted with caution as we performed a retrospective study with a relative
small control group.
PMID- 28417309
TI - Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.
AB - Cadmium (Cd) is a toxic environmental and occupational pollutant with reported
toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based
on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects
against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano
zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release
a great amount of Zn2+ in their environment. This research was carried out to
investigate the more potent properties of the metal zinc among sub-acute cadmium
intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium
chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different
sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body
weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg
bw) for 28 days. The experimental animals were decapitated, and the biochemical
biomarkers (enzymatic and non-enzymatic) were determined in their serum after
oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with
a one-way ANOVA and t test. P < 0.05 was considered as statistically significant.
The haematocrit (HCT) significantly increased and blood coagulation time
significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride,
total cholesterol, LDL, and free fatty acids increased significantly in the
cadmium- and nano-zinc-treated rats compared with the controls. However, albumin,
total protein, and HDLc significantly decreased in the cadmium- and nano-zinc
treated rats compared with the controls (P < 0.05). It seems that in the oral
administration of nano-zinc, the smaller sizes with low doses and the larger
sizes with high doses are more toxic than metallic zinc. In a few cases, an
inverse dose-dependent relationship was seen as well. This research showed that
in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not
suitable for protection against cadmium intoxication.
PMID- 28417310
TI - Telemedicine and Palliative Care: an Increasing Role in Supportive Oncology.
AB - With the emergence of telemedicine as a routine form of care in various venues,
the opportunities to use technology to care for the most vulnerable, most ill
cancer patients are extremely appealing. Increasingly, evidence supports early
integration of palliative care with standard oncologic care, supported by recent
NCCN guidelines to increase and improve access to palliative care. This review
looks at the use of telemedicine to expand access to palliative care as well as
provide better care for patients and families where travel is difficult, if not
impossible. When telemedicine has been used, often in Europe, for palliative
care, the results show improvements in symptom management, comfort with care as
well as patient and family satisfaction. One barrier to use of telemedicine is
the concerns with technology and technology-related complications in population
that is often elderly, frail and not always comfortable with non-face-to-face
physician care. There remain significant opportunities to explore this
intersection of supportive care and telemedicine.
PMID- 28417312
TI - The need for national registries for rare endocrine tumor syndromes.
PMID- 28417311
TI - Immune Checkpoint Inhibitors for Brain Metastases.
AB - PURPOSE OF REVIEW: Metastasis of cancer to the brain typically portends a poor
prognosis and often results in significant morbidity, including from the side
effects of treatment. More effective therapies for patients with brain metastases
are needed. The current treatment paradigm uses multiple modalities, including
surgery, radiation, and in some contexts, systemic chemotherapy and
immunotherapy. Immune checkpoint inhibitors are increasingly being used to treat
extracranial disease, and their effectiveness in the management of brain
metastases needs to be understood. RECENT FINDINGS: The evidence for immune
checkpoint inhibitors in the management of brain metastases is largely limited to
retrospective analyses of melanoma metastases and ipilimumab. Prospective
clinical trials of more active agents are under way, and tentative results
suggest activity. Immune checkpoint inhibitors have the potential to improve
outcomes in patients with brain metastases. Results of current clinical trials
will aid in determining the appropriate sequence or combination of local and
systemic therapies.
PMID- 28417313
TI - Impact of season and different vitamin D thresholds on prevalence of vitamin D
deficiency in epidemiological cohorts-a note of caution.
AB - PURPOSE: We investigated the impact of different cut-offs on the prevalence of 25
hydroxyvitamin D [25-(OH)D] deficiency. METHODS: We used baseline data of 4149
participants (45-75 years, 50% women) of the population-based Heinz Nixdorf
Recall study. Serum 25-(OH)D was measured with the Roche Cobas assay. Quartiles
(p25, p50, and p75) were calculated. Data were stratified by months, sex, and
age. According to the recommendations of 'Dachverband Osteologie', Endocrine
Society and National Institute of Health we used 25-(OH)D thresholds of 12, 20,
and 30 ng/ml to estimate vitamin D deficiency. RESULTS: Overall the median of 25
(OH)D was 19.8 ng/ml (p25 = 14.4 ng/ml, p75 = 26.6 ng/ml), with highest
concentrations in July (p50 = 23.8 ng/ml, p25 = 18.2 ng/ml, and p75 = 31.2 ng/ml)
and lowest in March (p50 = 15.8 ng/ml, p25 = 11.5 ng/ml, and p75 = 20.6 ng/ml).
Prevalence of vitamin D deficiency rose from 16, 51 up to 83% using the cut-offs
of <12, <20 ng/ml, and <30 ng/ml, respectively. With respect to seasonal
variance, prevalence of vitamin D deficiency rose to 92% in February/March using
the cut-off <30 ng/ml (<12: 28%, <20 ng/ml: 71%) whereas in June/July prevalence
of vitamin D deficiency decreased to 71% (<12: 6%, <20 ng/ml: 30%). The chance to
attest the diagnosis of vitamin D deficiency for cut-off 12 ng/ml in March is 6.4
fold higher than in June, for cut-off 20 ng/ml, 5.5-fold higher and for cut-off
30 ng/ml, 3.1-fold higher. CONCLUSIONS: Guidelines to define vitamin D deficiency
revealed extremely different prevalence rates ranging between 6 and 92%.
Accounting for collection time and antecedent sun exposure are important to
reduce bias in research studies and improve decision-making in clinical care.
Vitamin D thresholds have to be rethought.
PMID- 28417314
TI - Prognostic factors for gastroenteropancreatic neuroendocrine neoplasms (GEP
NENs): what's better?
PMID- 28417316
TI - A Web Resource for Levodopa-Induced Dyskinesia Genetics in Parkinson's Disease.
PMID- 28417315
TI - Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus,
Striatum, and Cerebellum of Developing Rats.
AB - Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities,
whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite
and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase
(CK) activity, mitochondrial respiration and redox status in hippocampus,
striatum and cerebellum of developing rats. Our in vitro results showed that
sulfite and thiosulfate decreased CK activity, whereas sulfite also increased
malondialdehyde (MDA) levels in all brain structures evaluated. Sulfite further
diminished mitochondrial respiration and increased DCFH oxidation and hydrogen
peroxide production in hippocampus. Sulfite-induced CK activity decrease was
prevented by melatonin (MEL), resveratrol (RSV), and dithiothreitol while
increase of MDA levels was prevented by MEL and RSV. Regarding the antioxidant
system, sulfite increased glutathione concentrations in hippocampus and striatum.
In addition, sulfite decreased the activities of glutathione peroxidase in all
brain structures, of glutathione S-transferase in hippocampus and cerebellum, and
of glutathione reductase in cerebellum. In vivo experiments performed with
intrahippocampal administration of sulfite demonstrated that this metabolite
increased superoxide dismutase activity without altering other biochemical
parameters in rat hippocampus. Our data suggest that impairment of energy
metabolism and redox status may be important pathomechanisms involved in brain
damage observed in individuals with SO deficiency.
PMID- 28417317
TI - Erratum to: The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in
nAMD: Systematic Review and Network Meta-Analysis.
PMID- 28417318
TI - Patient and Healthcare Professionals Preference for Brenzys vs. Enbrel
Autoinjector for Rheumatoid Arthritis: A Randomized Crossover Simulated-Use
Study.
AB - INTRODUCTION: Brenzys was developed as an etanercept biosimilar of Enbrel. The
aim of this study was to assess preference and perceived ease of use for the new
Brenzys autoinjector compared to the currently available marketed Enbrel MYCLIC
autoinjector (Australia) and Enbrel SureClick autoinjector (Canada) for the
treatment of rheumatoid arthritis (RA). Because RA affects manual dexterity, ease
of use of an autoinjector is a particularly important consideration in developing
effective self-delivery of long-term courses of therapy. METHODS: Patients (N =
191) reporting a diagnosis of RA and nurses and rheumatologists (N = 90) with
experience managing RA were shown how to use Brenzys and Enbrel autoinjectors (in
counterbalanced order between participants), then they used each autoinjector by
injecting into a pad simulating skin, and completed a questionnaire. Study
sessions took place in Australia and Canada. RESULTS: A binomial test showed that
significantly more patients indicated that the Brenzys autoinjector was easier to
use than the Enbrel autoinjector (79% reporting Brenzys easier to use; p < 0.001,
two-sided, 95% CI [73%, 85%]). In addition, significantly more nurses and
rheumatologists with experience managing RA also indicated that the Brenzys
autoinjector was easier to use (86%; p < 0.001, two-sided, 95% CI [77%, 92%) and
that they would recommend the buttonless Brenzys autoinjector over the Enbrel
autoinjector to patients (83%; p < 0.001, two-sided, 95% CI [74%, 90%]). Almost
all patients who reported past experience using an Enbrel autoinjector (N = 17)
reported on the basis of using the two devices in the study that they would
prefer to switch their device to the Brenzys autoinjector rather than continue
their course of therapy using the Enbrel autoinjector (16/17, 94%, 95% CI [71%,
100%]). CONCLUSION: On the basis of the study results, the Brenzys autoinjector
was rated statistically significantly easier to use, and was overall preferred by
patients and healthcare professionals with experience managing RA patients.
FUNDING: Merck & Co., Inc.
PMID- 28417319
TI - Cognitive Function and Vascular Risk Factors Among Older African American Adults.
AB - To evaluate the association between vascular risk factors and cognitive
impairment among older African American (AA) adults in a primary care clinic.
Participants included 96 AA adults aged 60 years or older who were evaluated for
global and domain-specific cognition. Participants were interviewed using the
Computerized Assessment of Memory and Cognitive Impairment (CAMCI). The
relationship between CAMCI cognitive domain scores and vascular risk factors were
examined using hierarchical regression models. Patients who smoked, those with
higher SBP/DBP values had lower accuracy rates on CAMCI cognitive domains
(attention, executive, memory).Those with higher BMI had better attention scores.
Patients with higher HbA1C values had worse verbal memory. Patients with higher
blood pressure were significantly faster in responding to tasks in the executive
domain. Primary care providers working with older AA adults with these VRFs could
implement cognitive screening earlier into their practice to reduce barriers of
seeking treatment.
PMID- 28417320
TI - Patient Reporting in the EU: Analysis of EudraVigilance Data.
AB - INTRODUCTION: New pharmacovigilance legislation was adopted in the EU in 2010 and
became operational in July 2012. The legislation placed an obligation on all
national competent authorities (NCAs) and marketing authorisation holders (MAHs)
to record and report cases of suspected adverse drug reactions (ADRs) received
from patients. OBJECTIVES: This descriptive study aims to provide insight into
patient reporting for the totality of the EU by querying the EudraVigilance (EV)
database for the period of 3 years before the new pharmacovigilance legislation
became operational and the 3 years after as well as comparing patient reports
with those from healthcare professionals (HCPs) where feasible. METHODS: We
queried the EV database for the following characteristics of patient and HCP
reports: demographics (patient sex and age), seriousness, reported ADR terms,
reported indications, number of ADRs per report, time to report an ADR, and most
reported substances. Wherever feasible, direct comparisons between patient
reports and HCP reports were performed using relative risks. RESULTS: The EV
database contained a total of 53,130 patient reports in the 3 years preceding the
legislation operation period and 113,371 in the 3 years after. Member states
contributing the most patient reports to the EV database were the Netherlands,
the UK, Germany, France and Italy. The results for indications and substances
show that patients were more likely than HCPs to report for genitourinary,
hormonal and reproductive indications. Patients reported more in general
disorders and administration site conditions Medical Dictionary for Regulatory
Activities (MedDRA) System Organ Class (SOC), whereas HCPs reported more
Preferred Terms (PTs) belonging in the Investigations SOC. However, 13 of the 20
reactions most frequently reported by patients were also among the top 20
reactions reported by HCPs. CONCLUSION: Patient reporting complemented reporting
by HCPs. Patients were motivated to report ADRs, especially those that affected
their quality of life. Sharing these results with NCAs and patient associations
can inform training and awareness on patient reporting.
PMID- 28417321
TI - Adjuvanted (AS03) A/H1N1 2009 Pandemic Influenza Vaccines and Solid Organ
Transplant Rejection: Systematic Signal Evaluation and Lessons Learnt.
AB - INTRODUCTION: We investigated a signal of solid organ transplant (SOT) rejection
after immunisation with (AS03) A/H1N1 2009 pandemic influenza vaccines. METHODS:
Potential immunological mechanisms were reviewed and quantitative analyses were
conducted. The feasibility of pharmacoepidemiological studies was explored.
RESULTS: Overall results, including data from a pharmacoepidemiological study,
support the safety of adjuvanted (AS03) pandemic influenza vaccination in SOT
recipients. The regulatory commitment to evaluate the signal through a stepwise
investigation was closed in 2014. CONCLUSION: Lessons learned highlight the
importance of investigating plausible biological mechanisms between vaccines and
potentially associated adverse outcomes, and the importance of selecting
appropriate study settings and designs for safety signal investigations.
PMID- 28417322
TI - Are midge swarms bound together by an effective velocity-dependent gravity?
AB - Midge swarms are a canonical example of collective animal behaviour where local
interactions do not clearly play a major role and yet the animals display group
level cohesion. The midges appear somewhat paradoxically to be tightly bound to
the swarm whilst at the same time weakly coupled inside it. The microscopic
origins of this behaviour have remained elusive. Models based on Newtonian
gravity do, however, agree well with experimental observations of laboratory
swarms. They are biologically plausible since gravitational interactions have
similitude with long-range acoustic and visual interactions, and they correctly
predict that individual attraction to the swarm centre increases linearly with
distance from the swarm centre. Here we show that the observed kinematics implies
that this attraction also increases with an individual's flight speed. We find
clear evidence for such an attractive force in experimental data.
PMID- 28417323
TI - Polymer chain collapse induced by many-body dipole correlations.
AB - We present a simple analytical theory of a flexible polymer chain dissolved in a
good solvent, carrying permanent freely oriented dipoles on the monomers. We take
into account the dipole correlations within the random phase approximation (RPA),
as well as a dielectric heterogeneity in the internal polymer volume relative to
the bulk solution. We demonstrate that the dipole correlations of monomers can be
taken into account as pairwise ones only when the polymer chain is in a coil
conformation. In this case the dipole correlations manifest themselves through
the Keesom interactions of the permanent dipoles. On the other hand, the
dielectric heterogeneity effect (dielectric mismatch effect) leads to the
effective interaction between the monomers of the polymeric coil. Both of these
effects can be taken into account by renormalizing the second virial coefficient
of the monomer-monomer volume interactions. We establish that in the case when
the solvent dielectric permittivity exceeds the dielectric permittivity of the
polymeric material, the dielectric mismatch effect competes with the dipole
attractive interactions, leading to polymer coil expansion. In the opposite case,
both the dielectric mismatch effect and the dipole attractive interaction lead to
the polymer coil collapse. We analyse the coil-globule transition caused by the
dipole correlations of monomers within the many-body theory. We demonstrate that
accounting for the dipole correlations higher than the pairwise ones smooths this
pure electrostatics driven coil-globule transition of the polymer chain.
PMID- 28417324
TI - Current remote sensing approaches to monitoring forest degradation in support of
countries measurement, reporting and verification (MRV) systems for REDD.
AB - Forest degradation is a global phenomenon and while being an important indicator
and precursor to further forest loss, carbon emissions due to degradation should
also be accounted for in national reporting within the frame of UN REDD+. At
regional to country scales, methods have been progressively developed to detect
and map forest degradation, with these based on multi-resolution optical,
synthetic aperture radar (SAR) and/or LiDAR data. However, there is no one single
method that can be applied to monitor forest degradation, largely due to the
specific nature of the degradation type or process and the timeframe over which
it is observed. The review assesses two main approaches to monitoring forest
degradation: first, where detection is indicated by a change in canopy cover or
proxies, and second, the quantification of loss (or gain) in above ground biomass
(AGB). The discussion only considers degradation that has a visible impact on the
forest canopy and is thus detectable by remote sensing. The first approach
encompasses methods that characterise the type of degradation and track
disturbance, detect gaps in, and fragmentation of, the forest canopy, and proxies
that provide evidence of forestry activity. Progress in these topics has seen the
extension of methods to higher resolution (both spatial and temporal) data to
better capture the disturbance signal, distinguish degraded and intact forest,
and monitor regrowth. Improvements in the reliability of mapping methods are
anticipated by SAR-optical data fusion and use of very high resolution data. The
second approach exploits EO sensors with known sensitivity to forest structure
and biomass and discusses monitoring efforts using repeat LiDAR and SAR data.
There has been progress in the capacity to discriminate forest age and growth
stage using data fusion methods and LiDAR height metrics. Interferometric SAR and
LiDAR have found new application in linking forest structure change to
degradation in tropical forests. Estimates of AGB change have been demonstrated
at national level using SAR and LiDAR-assisted approaches. Future improvements
are anticipated with the availability of next generation LiDAR sensors. Improved
access to relevant satellite data and best available methods are key to
operational forest degradation monitoring. Countries will need to prioritise
their monitoring efforts depending on the significance of the degradation,
balanced against available resources. A better understanding of the drivers and
impacts of degradation will help guide monitoring and restoration efforts.
Ultimately we want to restore ecosystem service and function in degraded forests
before the change is irreversible.
PMID- 28417325
TI - Microscopic and spectroscopic characterization of humic substances from a compost
amended copper contaminated soil: main features and their potential effects on Cu
immobilization.
AB - We characterized humic substances (HS) extracted from a Cu-contaminated soil
without compost addition (C) or amended with a wheat straw-based compost (WSC)
(H1), co-composted with Fe2O3 (H2), or co-composted with an allophane-rich soil
(H3). Extracted HS were characterized under electron microscopy (SEM/TEM), energy
dispersive X-ray (X-EDS), and Fourier transform infrared (FTIR) spectroscopy. In
addition, HS extracted from WSC (H4) were characterized at pH 4.0 and 8.0 with
descriptive purposes. At pH 4.0, globular structures of H4 were observed, some of
them aggregating within a large network. Contrariwise, at pH 8.0, long tubular
and disaggregated structures prevailed. TEM microscopy suggests organo-mineral
interactions at scales of 1 to 200 nm with iron oxide nanoparticles. HS extracted
from soil-compost incubations showed interactions at nanoscale with minerals and
crystal compounds into the organic matrix of HS. Bands associated to acidic
functional groups of HS may suggest potential sorption interactions with
transition metals. We conclude that metal ions and pH have an important role
controlling the morphology and configuration of HS from WSC. Characterization of
H4 extracted from WSC showed that physicochemical protection of HS could be
present in composting systems treated with inorganic materials. Finally, the
humified fractions obtained from compost-amended soils may have an important
effect on metal-retention, supporting their potential use in metal-contaminated
soils.
PMID- 28417326
TI - A time series analysis of environmental and metrological factors impact on
cutaneous leishmaniasis incidence in an endemic area of Dehloran, Iran.
AB - The aim of this study was to investigate the relationship between the
environmental and metrological variables and cutaneous leishmaniasis (CL)
transmission and its prediction in a region susceptible to this disease
prevalence using a time series model. The accurate locations of 4437 CL diagnosed
from 2011 to 2015 were obtained to be used in the time series model. Temperature,
number of days with temperature over 30 degrees C, and number of earthquake were
related to CL incidence using the Seasonal Auto-correlated Integrated Moving
Average (SARIMA) model according to the Box-Jenkins method. In addition, the
relationship between land use and surface soil type in 500- and 1000-m radius
around the CL patients were investigated. The SARIMA models showed significant
associations between environmental and meteorological variables and CL incidence
adjusted for seasonality and auto-correlation. The result indicated that there
are need more robust preventive programs in earthquake-prone areas with high
temperature and inceptisol soil type than other areas. In addition, the region
with these characteristics should be considered as high-risk areas for CL
prevalence.
PMID- 28417327
TI - Influence of land use and land cover on the spatial variability of dissolved
organic matter in multiple aquatic environments.
AB - Water quality of lakes, estuaries, and coastal areas serves as an indicator of
the overall health of aquatic ecosystems as well as the health of the terrestrial
ecosystem that drains to the water body. Land use and land cover plays not only a
significant role in controlling the quantity of the exported dissolved organic
matter (DOM) but also influences the quality of DOM via various biogeochemical
and biodegradation processes. We examined the characteristics and spatial
distribution of DOM in five major lakes, in an estuary, and in the coastal waters
of the Mississippi, USA, and investigated the influence of the land use and land
cover of their watersheds on the DOM composition. We employed absorption and
fluorescence spectroscopy including excitation-emission matrix (EEM) combined
with parallel factor (PARAFAC) analysis modeling techniques to determine optical
properties of DOM and its characteristics in this study. We developed a site
specific PARAFAC model to evaluate DOM characteristics resulting in five diverse
DOM compositions that included two terrestrial humic-like (C1 and C3), two
microbial humic-like (C2 and C5), and one protein-like (C4) DOM. Our results
showed elevated fluorescence levels of microbial humic-like or protein-like DOM
in the lakes and coastal waters, while the estuarine waters showed relatively
high fluorescence levels of terrestrial humic-like DOM. The results also showed
that percent forest and wetland coverage explained 68 and 82% variability,
respectively, in terrestrial humic-like DOM exports, while 87% variability in
microbially derived humiclike DOM was explained by percent agricultural lands.
Strong correlations between microbial humic-like DOM and fluorescence-derived DOM
indices such as biological index (BIX) and fluorescence index (FI) indicated
autochthonous characteristics in the lakes, while the estuary showed largely
allochthonous DOM of terrestrial origin. We also observed higher concentrations
of total dissolved phosphorous (TDP) and ammonium nitrogen (NH4-N) in coastal
waters potentially due to photodegradation of refractory DOM derived from the
sediment-bound organic matter in the coastal wetlands. This study highlights the
relationships between the DOM compositions in the water and the land use and land
cover in the watershed. The spatial variability of DOM in three different types
of aquatic environments enhances the understanding of the role of land use and
land cover in carbon cycling through export of organic matter to the aquatic
ecosystems..
PMID- 28417328
TI - Characterization and pyrolysis of Chlorella vulgaris and Arthrospira platensis:
potential of bio-oil and chemical production by Py-GC/MS analysis.
AB - Biofuels have been seen as potential sources to meet future energy demand as a
renewable and sustainable energy source. Despite the fact that the production
technology of first-generation biofuels is consolidated, these biofuels are
produced from foods crops such as grains, sugar cane, and vegetable oils
competing with food for crop use and agricultural land. In recent years, it was
found that microalgae have the potential to provide a viable alternative to
fossil fuels as source of biofuels without compromising food supplies or arable
land. On this scenario, this paper aims to demonstrate the energetic potential to
produce bio-oil and chemicals from microalgae Chlorella vulgaris and Arthrospira
platensis. The potential of these biomasses was evaluated in terms of physical
chemical characterization, thermogravimetric analysis, and analytical pyrolysis
interfaced with gas chromatograph (Py-GC/MS). The results show that C. vulgaris
and A. platensis are biomasses with a high heating value (24.60 and 22.43 MJ/kg)
and low ash content, showing a high percentage of volatile matter (72.49 and
79.42%). These characteristics confirm their energetic potential for conversion
process through pyrolysis, whereby some important aromatic compounds such as
toluene, styrene, and phenol were identified as pyrolysis products, which could
turn these microalgae a potential for biofuels and bioproduct production through
the pyrolysis.
PMID- 28417329
TI - Quantitative cancer risk assessment and local mortality burden for ambient air
pollution in an eastern Mediterranean City.
AB - Health risks posed by ambient air pollutants to the urban Lebanese population
have not been well characterized. The aim of this study is to assess cancer risk
and mortality burden of non-methane hydrocarbons (NMHCs) and particulates (PM)
based on two field-sampling campaigns conducted during summer and winter seasons
in Beirut. Seventy NMHCs were analyzed by TD-GC-FID. PM2.5 elemental carbon (EC)
components were examined using a Lab OC-EC aerosol Analyzer, and polycyclic
aromatic hydrocarbons were analyzed by GC-MS. The US EPA fraction-based approach
was used to assess non-cancer hazard and cancer risk for the hydrocarbon mixture,
and the UK Committee on Medical Effects of Air Pollutants (COMEAP) guidelines
were followed to determine the PM2.5 attributable mortality burden. The average
cumulative cancer risk exceeded the US EPA acceptable level (10-6) by 40-fold in
the summer and 30-fold in the winter. Benzene was found to be the highest
contributor to cancer risk (39-43%), followed by 1,3-butadiene (25-29%), both
originating from traffic gasoline evaporation and combustion. The EC attributable
average mortality fraction was 7.8-10%, while the average attributable number of
deaths (AD) and years of life lost (YLL) were found to be 257-327 and 3086-3923,
respectively. Our findings provide a baseline for future air monitoring programs,
and for interventions aiming at reducing cancer risk in this population.
PMID- 28417330
TI - Management of Nasal Fractures in Sports.
AB - Nasal fractures represent approximately 60% of all maxillofacial injuries that
occur in athletic activities; however, there are no current guidelines regarding
immediate sideline management of these injuries. Therefore, the purpose of this
article was to (1) summarize the anatomy, etiology, and incidence of nasal
fractures, and (2) evaluate the current body of literature regarding immediate on
field and subsequent outpatient management. It is imperative to establish that
the athlete's airway is not compromised and there are no other severe concomitant
injuries, such as a concussion, ocular injury, or leakage of cerebrospinal fluid.
Immediate closed reduction should not be attempted unless there is airway
compromise or the practitioner has experience in performing it. The majority of
athletes with these injuries in isolation may return to play; however, in our
practice, we recommend they wear a face mask for 6 weeks after their injury.
Despite our recommendations, we know there is a paucity of clinical studies on
immediate sideline and longer-term management. Future studies should focus on
establishing therapeutic algorithms that will allow physicians to make treatment
recommendations to patients with strong evidence to support their decision.
PMID- 28417331
TI - Use of High-Dose Oral Valacyclovir During an Intravenous Acyclovir Shortage: A
Retrospective Analysis of Tolerability and Drug Shortage Management.
AB - INTRODUCTION: In late 2011, a shortage of IV acyclovir led to the need to
empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV
acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or
encephalitis. This report describes the management of the most recent national IV
acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern
Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we
assessed the safety and tolerability of HDVA as an alternate to IV acyclovir
during this shortage. METHODS: We report the step-wise management, restrictions,
and guidelines implemented at NMH during a protracted IV acyclovir shortage. The
assessment of HDVA was a retrospective, observational cohort study of
hospitalized patients receiving HDVA between 1 January 2012 and 31 December 2013.
Appropriate demographic and treatment variables were collected. The primary
outcome was percentage of patients experiencing an adverse event. RESULTS: There
were 15 adult patients included in the study on a median daily dose of HDVA of 3
g (IQR 2-8). There were four patients with microbiologically confirmed viral CNS
infections (n = 1 HSV-1, n = 2 HSV-2, n = 1 VZV encephalitis) and eleven patients
with unknown causative pathogens. Six (40%) patients experienced at least one
adverse drug reaction (ADR) to HDVA (thrombocytopenia, 33.3%, n = 5; headache,
6.7%, n = 1; nausea, 6.7%, n = 1; rash, 6.7%, n = 1). One patient (6.7%) was
readmitted within 30 days with a suspected non-CNS infection. There were no
treatment discontinuations or symptomatic therapy necessary to treat any of the
ADRs. CONCLUSIONS: The shortage of IV acyclovir was successfully managed by the
ASP and HDVA appeared to be well tolerated when used as an alternative to IV
acyclovir.
PMID- 28417332
TI - Assessment of the prognostic and discriminating value of the novel bioscore
system for breast cancer; a SEER database analysis.
AB - BACKGROUND: An updated bioscore has been proposed within the context of the 8th
edition American Joint Committee on Cancer (AJCC) staging system for breast
cancer. This study seeks to validate the discriminating value of this bioscore
among non-metastatic breast cancer patients registered within the surveillance,
epidemiology, and end results (SEER) database. METHODS: Through SEER*Stat
program, SEER database (2010-2013) was accessed and bioscore was formulated for
each patient. Overall and cancer-specific survival analyses according to both
bioscore and AJCC pathological stages were conducted through Kaplan-Meier
analysis/log-rank testing, and multivariate analysis was conducted through a Cox
proportional model. RESULTS: A total of 181030 patients with non-metastatic,
surgically treated breast cancer were identified in the period from 2010 to 2013.
For overall and cancer-specific survival assessment according to the bioscore
system, P values for pairwise comparisons among different score points were
significant (P < 0.0001) except for the comparison between score 0 and score 1.
For cancer-specific survival assessment according to the AJCC stages, P values
for pairwise comparisons among different stages were significant (P < 0.0001)
except for the comparison between stages IIIB and IIIC. For overall survival
assessment according to the AJCC stages, P values for pairwise comparisons among
different stages were significant (P < 0.001) except for the comparison between
stages IA and IB. In a multivariate analysis, the following factors were
associated with better cancer-specific survival (earlier stage disease, ER
positivity, PR positivity, Her2 neu positivity, and nuclear grade) (P < 0.0001).
CONCLUSION: The current analysis confirms the prognostic utility of the bioscore
system and suggests it may be incorporated into decision-making algorithms for
non-metastatic breast cancer.
PMID- 28417333
TI - Immediate tissue expander or implant-based breast reconstruction does not
compromise the oncologic delivery of post-mastectomy radiotherapy (PMRT).
AB - PURPOSE: Increasingly, women are choosing immediate breast reconstruction (IBR)
following mastectomy. Reports have indicated IBR may compromise post-mastectomy
radiotherapy (PMRT). We investigated the impact of IBR on timing of PMRT, target
coverage, and doses to organs at risk in a modern radiotherapy practice using
advanced planning techniques. METHODS: Between 2013 and 2015, PMRT was delivered
to 116 patients (66 mastectomy alone, 50 IBR). PMRT was delivered with a median
dose of 50 Gy in 25 fractions. Left-sided patients were treated in breath-hold
under image guidance. Differences in dosimetric parameters and time to the
initiation of PMRT were assessed between patients with and without
reconstruction. RESULTS: Reconstructed patients were younger and had lower
clinical stage disease. Reconstruction did not significantly increase the mean
time to PMRT initiation (51 days reconstructed vs. 45 days non-reconstructed, p =
0.14) or the number of patients who initiated PMRT within 12 weeks of the last
therapeutic intervention (48/50 [96.0] vs. 61/66 [92.4%], p = 0.41). There was no
significant difference in the percentage of patients in whom the internal mammary
lymph nodes (IMNs) were targeted (72 vs. 80%, p = 0.29) or in IMN target coverage
(mean IMN V40.5 Gy 92.6 vs. 94.1%, p = 0.62). Reconstruction did not
significantly affect the mean ipsilateral lung V20 (25.4 vs. 26.4%, p = 0.37) or
the mean heart dose (2.2 vs. 2.1 Gy, p = 0.63). CONCLUSIONS: In a specialized
breast multidisciplinary practice, immediate breast reconstruction did not
significantly delay PMRT, compromise target coverage, or increase dose to organs
at risk.
PMID- 28417334
TI - Sleep quality, duration, and breast cancer aggressiveness.
AB - PURPOSE: Epidemiological studies suggest that short sleep duration and poor sleep
quality may increase breast cancer risk. However, whether sleep is associated
with breast tumor aggressiveness characteristics has largely been unexplored.
METHODS: The study included 4171 non-Hispanic whites (NHW) and 235 African
Americans (AA) diagnosed with incident, primary, invasive breast cancer in the
Women's Health Initiative (WHI) Observational Study (1994-2013). We used logistic
regression to examine the association of baseline sleep (sleep duration, sleep
quality, WHI Insomnia Rating Scale) with tumor grade, stage, hormone receptor
status, HER2 status. RESULTS: In NHW, women who reported 6 h of sleep/night were
more likely to have tumors classified as regional/distant stage at diagnosis
compared to women who slept 7-8 h/night (adjusted odds ratio (OR): 1.25, 95%
confidence interval (CI): 1.05-1.48). AA women who reported their typical night's
sleep as 'average quality' or 'restless or very restless sleep' were more likely
to be diagnosed with triple-negative tumors than those who reported 'sound or
restful' sleep (adjusted ORs: 2.91 (1.11, 7.63) and 3.74 (1.10, 12.77),
respectively). CONCLUSIONS: Our findings provide indications that aspects of
sleep (sleep duration and quality), partially modifiable health behaviors, may be
associated with development of aggressive tumor characteristics in postmenopausal
women. The role of these sleep attributes may differ for NHW and AA women;
however, further study in robust, racial diverse samples is needed. This study
provides evidence that facets of sleep behavior are associated with the
development of aggressive tumor features and these associations differ by race.
PMID- 28417335
TI - Poor prognosis of patients with triple-negative breast cancer can be stratified
by RANK and RANKL dual expression.
AB - PURPOSE: As clinical studies have correlated RANK expression levels with survival
in breast cancer, and that RANK signaling is dependent on its cognate ligand
RANKL, we hypothesized that dual protein expression further stratifies the poor
outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC
using genomic databases, cell lines and in a tissue microarray of curated primary
tumor samples derived from 87 patients with TNBC. RANK expression was evaluated
either by Mann-Whitney U test on log-normalized gene expression data or by
Student's t test on FACS data. Analysis of RANK and RANKL immunostaining was
calculated by H-score, and correlations to clinical factors performed using chi 2
or Fisher's exact test. Associations with RFS and OS were assessed using
univariate and multivariate Cox proportional hazard models. Survival estimates
were generated using the Kaplan-Meier method. RESULTS: In three distinct datasets
spanning 684 samples, RANK mRNA expression was higher in primary tumors derived
from TNBC patients than from those with other molecular subtypes (P < 0.01). Cell
surface-localized RANK protein was consistently higher in TNBC cell lines (P =
0.037). In clinical samples, TNBC patients that expressed both RANK and RANKL
proteins had significantly worse RFS (P = 0.0032) and OS (P = 0.004) than
patients with RANK-positive, RANKL-negative tumors. RANKL was an independent,
poor prognostic factor for RFS (P = 0.04) and OS (P = 0.01) in multivariate
analysis in samples that expressed both RANK and RANKL. CONCLUSIONS: RANK and
RANKL co-expression is associated with poor RFS and OS in patients with TNBC.
PMID- 28417336
TI - Treatment of Depression in Adults with Fabry Disease.
AB - Fabry disease (FD) is a genetic X-linked, multisystemic, progressive lysosomal
storage disorder (LSD). Depression has emerged as a disease complication, with
prevalence estimates ranging from 15 to 62%. This is a pilot study examining the
effects of psychological counseling for depression in FD on depression, adaptive
functioning (AF), quality of life (QOL), and subjective pain experience.
Telecounseling was also piloted, as it has beneficial effects in other chronic
diseases which make in-person counseling problematic. Subjects completed 6 months
of in-person or telecounseling with the same health psychologist, followed by 6
months without counseling. Self-report measures of depression, AF, QOL, and
subjective pain were completed every 3 months. All subjects experienced
improvements in depression, which were sustained during the follow-up period.
Improvements in depression were correlated with improvements in mental health QOL
and subjective pain severity, while improvements in mental health QOL were
correlated with improvements in AF. While statistical comparison between
counseling modes was not possible with the given sample size, relevant
observations were noted. Recommendations for future research include replication
of results with a larger sample size and a longer counseling period. The use of
video counseling may be beneficial. In conclusion, the present pilot study
supports the efficacy of psychological treatment for depression in people with
FD, highlighting the importance of having health psychologists housed in LSD
treatment centers, rather than specialty psychology/psychiatry settings, to
increase participation and decrease potential obstacles to access due to
perceived stigma.
PMID- 28417337
TI - Descemet stripping automated endothelial keratoplasty versus descemet membrane
endothelial keratoplasty: a meta-analysis.
AB - PURPOSE: To evaluate the efficacy and safety of descemet stripping automated
endothelial keratoplasty (DSAEK) compared with descemet membrane endothelial
keratoplasty (DMEK). METHODS: Databases including PubMed, EMBASE, and Cochrane
Library were searched to find studies that compared DSAEK and DMEK outcomes.
Efficacy parameters were the postoperative best-corrected visual acuity (BCVA)
and spherical equivalent (SE). Safety parameters were postoperative endothelial
cell loss (ECL), air injection (rebubbling), graft failure, graft rejection, and
high intraocular pressure (IOP). Results from last visit were pooled for the
analyses because the follow-up ranged from 3 to 24 months. RESULTS: A total of 7
trials including 433 eyes were selected for this meta-analysis. BCVA was reported
in all 7 studies, ECL% and rebubbling rate were reported in 6, and the remaining
outcomes were reported in only 3 or 2 studies. Postoperative logMAR BCVA was
significantly better for DMEK than that for DSAEK (P < 0.00001). More patients
achieved the postoperative BCVA >= 20/25 and 20/20 in DMEK group than that in
DSAEK (P > 0.001), whereas the proportion of patients whose postoperative BCVA >=
20/40 and the amount of SE did not differ statistically (P = 0.32 and P = 0.50,
respectively). The DSAEK group has a significantly lower frequency of rebubbling
than the DMEK group (P < 0.0001). The postoperative ECL%, graft failure, graft
rejection, and high IOP were comparable between the 2 groups (all P values
>0.05). CONCLUSIONS: Our meta-analysis suggests that DMEK provided better visual
outcomes with similar safety when compared to DSAEK. Given the limited sample
size, further investigations are needed to validate these findings.
PMID- 28417338
TI - Accessibility, accountability, affordability: healthcare policy in orthopedic
trauma.
AB - PURPOSE OF REVIEW: This review provides historical background on trauma care in
the USA and summarizes contemporary trauma-related health policy issues. It is a
primer for orthopedic surgeons who want to promote improvements in research,
delivery, and cost reduction in trauma care. RECENT FINDINGS: As of 2010, funding
for trauma research accounted for only 0.02% of all National Institutes of Health
research funding. This is disproportionate to the societal burden of traumatic
injury, which is the leading cause of death and disability among people aged 1 to
46 years in the USA. The diagnosis-related group model of hospital reimbursement
penalizes level-I trauma centers, which typically treat the most severely injured
patients. Treatment of traumatic injury at level-I and level-II trauma centers is
associated with lower rates of major complications and death compared with
treatment at non-trauma centers. Patient proximity to trauma centers has been
positively correlated with survival after traumatic injury. Inadequate funding
has been cited as a reason for recent closures of trauma centers. Orthopedic
surgeons have a responsibility to engage in efforts to improve the quality,
accessibility, and affordability of trauma care. This can be done by advocating
for greater funding for trauma research; choosing the most cost-effective,
patient-appropriate orthopedic implants; supporting the implementation of a
national trauma system; leading high-quality research of trauma patient outcomes;
and advocating for greater accessibility to level-I trauma centers for
underserved populations.
PMID- 28417339
TI - Expression and function of the small-conductance Ca2+-activated K+ channel is
decreased in urinary bladder smooth muscle cells from female guinea pig with
partial bladder outlet obstruction.
AB - PURPOSE: Overactive bladder (OAB), usually accompanied by partial bladder outlet
obstruction (PBOO), is associated with detrusor overactivity (DO) which is
related to the increased urinary bladder smooth muscle (UBSM) cells excitability.
Small-conductance Ca2+-activated K+ (SK) channels play a constitutive regulatory
role of UBSM excitability and contractility. PBOO is associated with the
decreased SK channels mRNA expression and the attenuated regulative effect of SK
channels on UBSM contractility. However, the regulation of SK channels in PBOO
UBSM cell excitability is less clear. Here, we tested the hypothesis that PBOO is
associated with decreased expression and function of SK channels in UBSM cells
and that SK channels are a potential target for the treatment of OAB. METHODS:
Cystometry indicated that DO was achieved 2 weeks after PBOO in female guinea
pigs. Using this animal model, we conducted single-cell quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) and patch-clamp
electrophysiology. RESULTS: The single-cell qRT-PCR experiments indicated the
reduced SK channel mRNA expression in PBOO UBSM cells. Patch-clamp studies
revealed that NS309 had a diminished effect on resting membrane potential
hyperpolarization via the activation of SK channels in PBOO UBSM cells. Moreover,
attenuated whole-cell SK channel currents were demonstrated in PBOO UBSM cells.
CONCLUSIONS: The attenuated expression and function of SK channels, which results
in the increased UBSM cells excitability and contributes to DO, was discovered in
PBOO UBSM cells, suggesting that SK channels might be potential therapeutic
targets for the control of OAB.
PMID- 28417341
TI - External validation of a nomogram including the computed tomography imaging score
to predict indolent renal masses.
AB - PURPOSE: To assess a nomogram including the computed tomography (CT) score and
body mass index (BMI) that was constructed to predict indolent diseases in a
cohort of patients with renal masses. MATERIALS AND METHODS: The data collected
from patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN)
between January 2012 and September 2016 were analyzed. Two urologic surgeons and
a radiologist reviewed the images to determine the CT score. Postoperative
pathological assessment was performed to categorize renal masses as either
indolent or aggressive. The BMI and CT scores were included in the nomogram to
identify the risk of indolent disease. The performance of the novel model was
assessed by using discrimination, calibration plots, and decision curve analysis
(DCA). RESULTS: Two hundred and two participants (with 202 masses) who underwent
RN or PN were included; 37% of the masses were indolent. The predictive
performances of the nomogram revealed areas under the curve of 0.866 for masses
of all cases and 0.808 for cT1 masses without visible fat. DCA revealed that the
nomogram was moderately clinically useful. The calibration plots showed a
reasonable calibration and systematic overestimation of indolent disease based on
nomogram predictions. CONCLUSIONS: The CT score nomogram discriminated well
between indolent and aggressive renal masses. The model had a reasonable
calibration in our cohort for discriminating indolent from aggressive lesions.
Further research to validate and assess the nomogram is required.
PMID- 28417340
TI - Preconditioning of primary human renal proximal tubular epithelial cells without
tryptophan increases survival under hypoxia by inducing autophagy.
AB - PURPOSE: Hypoxia plays a significant role in the pathogenesis of acute kidney
injury (AKI). Autophagy protects from AKI. Amino acid deprivation induces
autophagy. The effect of L-tryptophan depletion on survival and autophagy in
cultures of renal proximal tubular epithelial cells (RPTECs) under hypoxia was
evaluated. METHODS: RPTECs were preconditioned in a medium containing or not
tryptophan, following culture under hypoxia and treatment with or without the
autophagy inhibitor chloroquine. Cell survival was assessed by cell imaging, the
level of certain proteins by western blotting and cellular ATP fluorometrically.
RESULTS: Preconditioning of RPTECs in a medium without tryptophan activated
general control nonderepressible 2 kinase and induced changes that favored
autophagy and cell survival under hypoxic conditions. Additionally, it increased
cellular ATP, while it inhibited apoptosis. Inhibition of autophagy nullified the
induced increase in cellular ATP and cell survival by the absence of tryptophan.
The absence of tryptophan increased p53, although its effect on p53's
transcriptional targets was heterogeneous. In accordance with the decreased
apoptosis, expression of p21 increased, while expression of Bax decreased. The
expression of BNIP3L, which may be pro-apoptotic or pro-autophagic, increased.
Considering the decreased apoptosis, it is likely that tryptophan depletion
enhances autophagy through a p53-mediated increase of BNIP3L. CONCLUSION:
Preconditioning of primary human RPTECs in a medium without tryptophan increases
their survival under hypoxia by inducing autophagy. Identifying new molecular
mechanisms that protect renal tissue from hypoxia could be proved clinically
important in the prevention of AKI.
PMID- 28417342
TI - Adipose tissue-derived stem cell therapy for erectile dysfunction in rats: a
systematic review and meta-analysis.
AB - OBJECTIVE: We aimed to systematically assess the effect of adipose tissue-derived
stem cell (ADSC) therapy and its influential factors on the treatment of erectile
dysfunction (ED) in rats. METHODS: Two authors independently searched for
published studies through PubMed and EMBASE from study inception until August 31,
2016. A meta-analysis was used to combine the effect estimate from the published
studies. A subgroup analysis was performed to identify the effect of some
influential factors. The pooled standardized mean differences (SMDs) with 95%
confidence intervals (CIs) were calculated by a fixed-effects or random-effects
model analysis. RESULTS: Twenty studies with a total of 248 rats were included in
this meta-analysis. The pooled analysis showed that ADSC therapy significantly
increased the ratio of intracavernous pressure and mean arterial pressure
(ICP/MAP; SMD 3.46, 95% CI 2.85-4.06; P < 0.001) compared to control therapy. The
levels of neuronal nitric oxide synthase (nNOS; SMD 6.37, 95% CI 4.35-8.39; P <
0.001), the cavernous smooth muscle content (CSMC; SMD 3.65, 95% CI 2.65-4.65; P
< 0.001), the ratio of cavernous smooth muscle and collagen (CSM/collagen; SMD
4.16, 95% CI 2.59-5.72; P < 0.001), and the cyclic guanosine monophosphate (cGMP;
SMD 7.12, 95% CI 2.76-11.48; P = 0.001) were higher following ADSC therapy than
following control therapy. Subgroup analysis showed that ADSCs modified by growth
or neurotrophic factors significantly recovered erectile function (P < 0.001)
compared with ADSC therapy. CONCLUSION: The adequate data indicated that ADSC
therapy recovered erectile function and regenerated cavernous structures in ED
rats, and ADSCs modified by some growth and neurotrophic factors accelerated the
recovery of erectile function and cavernous structures in ED rats.
PMID- 28417343
TI - Adjuvant Therapy for Melanoma.
AB - Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at
high risk for disease recurrence and death targets residual micrometastatic
disease which is the source of future local or distant relapse. Interferon-alfa
(IFNalpha) has been the most extensively studied in regimens that varied by
dosage, route of administration, formulation, and duration of therapy. Most
regimens have demonstrated improvements in relapse-free survival (RFS), while the
regimen administered at high dosage (HDI) showed improvements in overall survival
(OS) in two out of three RCTs. HDI benefits as measured by the hazard ratios (HR)
in E1684 (vs. observation), E1690 (vs. observation), and E1694 (vs. vaccine)
trials were estimated at 0.61, 0.78, and 0.67 (RFS) and 0.67, 1.0, and 0.72 (OS)
when first reported with lesser estimates on later updates. Pegylated IFNalpha
(peg-IFN) as studied in the European Organisation for Research and Treatment of
Cancer (EORTC) 18991 trial in patients with stage III melanoma significantly
reduced the risk of relapse (HR 0.87) with no impact on OS. More recently (EORTC
18071), ipilimumab at the high dose of 10 mg/kg was shown to significantly
improve RFS (HR 0.76) and OS (HR 0.72) of stage III melanoma patients but at a
significant cost in terms of immune-related toxicities. Ongoing adjuvant studies
are testing ipilimumab at 3 or 10 mg/kg versus HDI (E1609) and the anti-PD-1
antibodies nivolumab (CheckMate 238) and pembrolizumab (KEYNOTE-054 and S1404).
PMID- 28417344
TI - Biotherapy in Inflammatory Diseases of the CNS: Current Knowledge and
Applications.
AB - OPINION STATEMENT: Biotherapy represents an innovative therapeutic approach that
includes immunotherapy (vaccines, apheresis, and antibodies); gene therapy; and
stem cell transplants. Their development helps to cross the bridge from bench to
bedside and brings new hope of a cure for severe diseases in different fields of
medicine. In neurology, a growing range of applications is being developed for
these medications. Valuable results are now available in the field of
autoimmunity, neuro-oncology, paraneoplastic manifestations, and
neurodegenerative disorders. In this review, we examine the current and future
applications of biotherapy in the field of inflammation of the central nervous
system. We demonstrate its contribution in clinical practice, where it has
enabled a significant level of effectiveness to be achieved. Indeed, the efficacy
of these new biodrugs provides a solution for patients refractory to standard
therapies, such as intravenous immunoglobulins in limbic encephalitis, plasma
exchanges in neuromyelitis optica and anti-CD20 monoclonal antibodies in multiple
sclerosis. They also mark the first steps towards individualized medicine.
PMID- 28417345
TI - Imaging Markers for Monitoring Disease Activity in Multiple Sclerosis.
AB - OPINION STATEMENT: Multiple sclerosis (MS) is an immune-mediated disease
affecting the central nervous system (CNS). Magnetic resonance imaging (MRI) has
long been recognized as an important tool in the diagnosis of MS. It is
increasingly recognized that in addition to its role in diagnosis, MRI can play a
key role as a noninvasive tool for prognostication, disease monitoring,
assessment of treatment efficacy, and safety monitoring of disease-modifying
therapies (DMTs). A confluence of factors, including increased availability of
MRI, development of improved MRI techniques, and increased availability of DMTs
have contributed to the expanding role of MRI in MS clinical care. As the
clinical use of MRI in MS expands, it is important that MRI protocols amongst
clinical centers are standardized. Here, we summarize recent evidence supporting
the use of MRI in clinical practice, summarize various clinical guidelines and
recommendations for the use of MRI in MS disease monitoring, and provide our
recommendations for standardized MRI protocols.
PMID- 28417346
TI - [Role of primaquine in malaria control and elimination in French-speaking
Africa].
AB - Primaquine, an 8-aminoquinoline, is a relatively unknown and underutilized drug
in French-speaking African countries. It acts against the liver stage parasites
of all human malaria species, asexual blood stages of Plasmodium vivax and, to a
lesser degree, Plasmodium falciparum; P. falciparum mature gametocytes, and P.
vivax and Plasmodium ovale hypnozoites. Gastrointestinal disturbances are its
most common side effects. The clinical utility of primaquine is limited due to
its hematological side effects in individuals with glucose-6-phosphate
dehydrogenase (G6PD) deficiency and other contraindications (pregnant woman,
breastfeeding woman, infants less than 6 months old). In the light of the recent
recommendations of the World Health Organization (WHO), we propose to examine how
primaquine can be used in French-speaking Africa to improve malaria control and
move towards malaria elimination. Two indications supported by the WHO are of
relevance in Africa. First, artemisinin-based combination therapies and
primaquine given as a single low dose (0.25 mg base/kg) are effective to kill
asexual and sexual parasites of P. falciparum, are well-tolerated, and have very
little risk even in mild to moderate G6PD-deficient patients. This strategy may
be helpful to contain transmission in an area in Africa where P. falciparum
malaria incidence has decreased considerably. There is an ethical concern in
administering primaquine as a gametocytocide as it does not confer any direct
benefit to the treated patient. However, the single low-dose primaquine is most
likely associated with very low risk for adverse hematological effects, and WHO
recommends its use even without prior G6PD testing. In our opinion, clinical
studies including G6PD test should be conducted to assess the safety of low-dose
primaquine in African patients. Second, primaquine is effective and necessary for
radical treatment of P. vivax and P. ovale, but the standard 14-day treatment
(0.25-0.5 mg base/kg/day) is not recommended in patients with G6PD deficiency.
Prior G6PD testing is required before prescribing primaquine for radical
treatment. The use of primaquine for radical treatment in patients without
contraindications does not raise any major ethical problem since the probability
of relapse in patients who do not receive anti-hypnozoite treatment can be
relatively high and each relapse can cause or aggravate anemia, especially in
children. In our opinion, patients with mild or moderate G6PD deficiency should
not be treated with primaquine at present. Further clinical studies are necessary
to define the role of this drug for radical treatment in G6PD-deficient African
patients. Without primaquine, the eventual elimination of P. vivax and P. ovale
malaria appears to be very difficult. Updated epidemiological data on G6PD, Duffy
antigen, and the current distribution of and burden due to P. vivax and P. ovale
are required for a rational use of primaquine in the African continent. Moreover,
clinical studies on primaquine are required in Africa.
PMID- 28417347
TI - [Serological markers of viral hepatitis B and C in children with sickle cell
disease monitored in the Pediatrics Department at the University Hospital of Bobo
Dioulasso (Burkina Faso)].
AB - Viral hepatitis B and C are universal public health problems. Burkina Faso is a
high endemic area for hepatitis B. Patients with sickle cell disease are at risk.
The aim of this study was to investigate and quantify the serological markers of
viral hepatitis B and C among pediatric patients with sickle cell disease. This
was a descriptive cross-sectional study, which took place from July to November
2014 at the Department of Pediatrics, University Hospital of Bobo- Dioulasso. The
study included 44 SS and 26 SC sickle cell patients. General data (age, gender)
and medical information (vaccinations, medical history including transfusion)
were collected. Blood samples were taken for research and titration of
serological markers of hepatitis viruses B and C with a commercial Elisa test on
the ARCHITECT i1000(r) automat of Abbott Laboratories. The mean age of the
patients was 7.98 years. Seventeen patients (13 SS and SC 4) had already been
transfused at least once. The transfusion rate was significantly higher among the
SS patients than among SC (29.5% and 15.3% respectively) patients. No patient
with HBs Ag was been found. In two patients, the anti-HBc Ab was found alone. In
33% of cases, no markers of hepatitis B were found. Less than 20% of children
fully vaccinated (N = 45) had a protective level of anti-HBs Ab (greater than 10
IU/l). The prevalence of anti-VHC Ab was 2.8%. No case of HBV-HCV co-infection
was found. The prevention of infection is an important part of the management of
sickle cell patients. Immunization against hepatitis B should be systematic. The
results of this study assume that blood safety was good.
PMID- 28417348
TI - Elevated progesterone and its impact on birth weight after fresh embryo
transfers.
AB - PURPOSE: The purpose of the study was to examine the association between serum
progesterone levels on the day of hCG administration and birth weight among
singleton live births after fresh embryo transfer. METHODS: This study was
conducted as a retrospective cohort database analysis on patients who underwent
IVF treatment cycles from January 2004 to April 2012. The study was performed at
a University affiliated private infertility practice. All cycles that had
achieved a singleton live birth after fresh embryo transfer and for which
progesterone was measured on the day of hCG administration were examined.
Generalized linear models were used to calculate mean birth weight and z-scores.
RESULTS: We analyzed 817 fresh IVF embryo transfers in which birth weight,
gestational age, and progesterone (ng/mL) level on day of hCG administration were
documented. While there was a decrease in birth weight as progesterone quartile
[<=0.54; >0.54 to <=0.81; >0.81 to <=1.17; >1.17 ng/mL] increased, the difference
in mean birth weights among the four quartiles was not statistically significant
(p = 0.11) after adjusting for maternal age and peak estradiol levels. When
dichotomizing based on a serum progesterone considered clinically elevated,
cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton
birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with
progesterone <=2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after
adjusting for maternal age and estradiol. CONCLUSION: We demonstrated that
caution should be exercised when performing fresh embryo transfers with elevated
progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead
to lower birth weight.
PMID- 28417350
TI - Does DHEA supplementation in IVF patients result in supraphysiological DHEA-S
serum concentrations?
PMID- 28417349
TI - A higher prevalence of endometriosis among Asian women does not contribute to
poorer IVF outcomes.
AB - PURPOSE: The purpose of the study was to determine whether diagnosis of
endometriosis or endometriosis with endometrioma influences in vitro
fertilization (IVF) outcomes in an ethnically diverse population. METHODS: Women
undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31,
2009, at a university-affiliated infertility clinic, were retrospectively
assessed for an endometriosis diagnosis. Differences in prevalence of
endometriosis by ethnicity were determined, as well as differences in IVF success
by ethnicity, with a focus on country of origin for Asian women. A multivariate
model was generated to assess the relative contributions of country of origin and
endometriosis to chance of clinical pregnancy with IVF. RESULTS: Endometriosis
was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of
endometrioma. Endometriosis prevalence in Asian women was significantly greater
than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01),
Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically
were more likely to have endometriosis than Caucasian women, although there was
no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo
quality, and fertilization rates did not relate to endometriosis. Clinical
pregnancy rates were significantly lower for Asian women, specifically in Indian
(p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to
Caucasian women, even after controlling for endometriosis status. CONCLUSIONS:
The prevalence of endometriosis appears to be higher in Filipino, Indian,
Japanese, and Korean women presenting for IVF treatment than for Caucasian women;
however, the discrepancy in IVF outcomes was conditionally independent of the
presence of endometriosis. Future research should focus on improving pregnancy
outcomes for Asian populations whether or not they are affected by endometriosis,
specifically in the form of longitudinal studies where exposures can be captured
prior to endometriosis diagnoses and infertility treatment.
PMID- 28417351
TI - Detrimental effect of maternal and post-weaning high-fat diet on the reproductive
function in the adult female offspring rat: roles of insulin-like growth factor 2
and the ovarian circadian clock.
AB - PURPOSE: We evaluate the impact of maternal and post-weaning high-fat (HF) diet
on ovarian follicular population, steroidogenesis, and gene expression with a
focus on the circadian clock system and insulin-like growth factor 2 (Igf2) in
adult offspring ovaries, and to elucidate whether a maternal and post-weaning
diet confers similar risks. METHODS: Virgin Sprague-Dawley rats were fed with
normal chow (C) diet or HF diet for 5 weeks before mating, during gestation, and
lactation. Female offspring were fed with the C or HF diet from weaning to 6
months of age, resulting in four study groups (n = 6 per group): C/C, C/HF, HF/C,
and HF/HF. RESULTS: Ovaries from offspring exposed to post-weaning HF diet (i.e.,
the C/HF and HF/HF groups) had a decrease in small follicle numbers, but with
similar numbers of antral follicles and corpora lutea. Offspring from HF-fed dams
(i.e., the HF/C and HF/HF groups) had increased plasma estradiol concentrations
and decreased luteinizing hormone levels at 6 months of age. In addition, Igf2
and each of the circadian rhythm core genes Clock, Per1, Per2, and Per3 were
increased in the ovaries of offspring exposed to maternal HF diet (both HF/C and
HF/HF groups). CONCLUSIONS: Maternal and post-weaning HF diet programs the
reproductive profile of the female offspring in adult life through different
manners. Post-weaning HF intake resulted in the reduction of small follicles in
adulthood, whereas maternal HF diet had long-term deleterious consequences on
female offspring steroidogenesis and coincided with alteration of the
upregulation of the imprinted gene Igf2 and changes in ovarian circadian rhythms.
PMID- 28417352
TI - Follicular ADAMTS-1 and aggrecan levels in polycystic ovary syndrome.
AB - PURPOSE: Polycystic ovary syndrome (PCOS) is the most common cause of ovulatory
dysfunction and female infertility. The etiopathogenetic mechanisms of PCOS have
been studied for many years, although exact causes remain unclear. It has been
demonstrated that proteoglycan degradation by a disintegrin-like
metalloproteinase with thrombospondin type motifs-1 (ADAMTS-1) is essential for
ovulation and fertilization. The objective of our study is to analyze the levels
of ADAMTS-1 and aggrecan in the follicular fluid (FF) of PCOS patients compared
with normal ovulatory women and to determine whether these markers could be a
predictor of in vitro fertilization (IVF) success in PCOS patients. METHODS:
Women with PCOS (n = 21) and normal ovulatory controls (n = 22) undergoing IVF
treatment were recruited. ADAMTS-1 and aggrecan levels were analyzed with enzyme
linked immunosorbent assay (ELISA) and compared between PCOS and normal ovulatory
controls. The predictor effect of ADAMTS-1 and aggrecan on fertilization rate and
implantation was evaluated. RESULTS: FF ADAMTS-1 and aggrecan levels increased in
women with PCOS compared to controls. Elevated ADAMTS-1 levels but not aggrecan
were related to increased implantation in PCOS. CONCLUSION: Our study
demonstrated that altered levels of ADAMTS-1 and aggrecan may have a partial role
in the etiopathogenesis of PCOS, and ADAMTS-1 could be a predictive marker for
implantation success in PCOS patients.
PMID- 28417353
TI - The electronic medical record in anesthesiology: a standard of quality healthcare
and patient safety.
PMID- 28417354
TI - Perioperative epidural analgesia is not associated with increased survival from
renal cell cancer, but overall survival may be improved: a retrospective chart
review.
AB - PURPOSE: We investigated the possible association between perioperative epidural
and both cancer-specific survival (CSS) and overall survival (OS) in patients
undergoing partial or radical nephrectomy for localized renal cell carcinoma
(RCC). METHODS: A retrospective chart review was performed on patients who
underwent complete surgical resection of localized RCC from 1994-2008 at our
institution. Baseline demographics and pathological and survival data were
collected. Patients with clinically or pathologically positive lymph nodes or
metastatic disease at the time of surgery were excluded. Patients with
pathologically positive surgical margins were also excluded. Patients were
divided into two groups, systemic analgesia and epidural analgesia. Multivariable
Cox regression analysis was used to determine CSS and OS, and survival curves
were generated using the Kaplan-Meier method. RESULTS: Four hundred thirty-eight
patients were included in the analysis. Baseline characteristics of both groups
were similar. Median follow-up was 77 months. On multivariable analysis, patient
age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02 to 1.07),
epidural status (HR, 0.5; 95% CI, 0.4 to 0.8), year of surgery (HR, 0.9; 95% CI,
0.89 to 0.95), and pathologic T-stage (pT-stage) >= 2 (pT-stage2: HR, 2.2; 95%
CI, 1.2 to 4.1 and pT-stage3: HR, 3.1; 95% CI, 2.0 to 4.7) were independent
predictors of OS. Nevertheless, epidural status did not significantly predict CSS
(P = 0.73), while T-stage and year of surgery maintained their respective
predictive significance. Tumour grade did not significantly affect OS or CSS.
CONCLUSIONS: Our retrospective analysis suggests that epidural at the time of
surgical excision of localized RCC does not significantly impact CSS.
Nevertheless, use of epidural was associated with significantly improved OS.
Future prospective clinical and laboratory studies are warranted in order to
characterize these associations further and determine the underlying mechanisms.
PMID- 28417356
TI - A Low-Volume, Parallel Copper-Bicinchoninic Acid (BCA) Assay for Glycoside
Hydrolases.
AB - The quantitation of liberated reducing sugars by the copper-bicinchoninic acid
(BCA) assay provides a highly sensitive method for the measurement of glycoside
hydrolase (GH) activity, particularly on soluble polysaccharide substrates. Here,
we describe a straightforward method adapted to low-volume polymerase chain
reaction (PCR) tubes which enables the rapid, parallel determination of GH
kinetics in applications ranging from initial activity screening and assay
optimization, to precise Michaelis-Menten analysis.
PMID- 28417355
TI - Radiofrequency versus microwave ablation for treatment of the lung tumours:
LUMIRA (lung microwave radiofrequency) randomized trial.
AB - The LUMIRA trial evaluated the effectiveness of radiofrequency (RFA) and
microwave ablation (MWA) in lung tumours ablation and defining more precisely
their fields of application. It is a controlled prospective multi-centre random
trial with 1:1 randomization. Fifty-two patients in stage IV disease (15 females
and 37 males, mean age 69 y.o., range 40-87) were included. We randomized the
patients in two different subgroups: MWA group and RFA group. For each group, we
evaluated the technical and clinical success, the overall survival and
complication rate. Inter-group difference was compared using Chi-square test or
Fisher's exact test for categorical variables and one-way ANOVA test for
continuous variables. For RFA group, there was a significant reduction in tumour
size only between 6 and 12 months (p value = 0.0014). For MWA group, there was a
significant reduction in tumour size between 6 and 12 months (p value = 0.0003)
and between pre-therapy and 12 months (p value = 0.0215). There were not
significant differences between the two groups in terms of survival time (p value
= 0.883), while the pain level in MWA group was significantly less than in RFA
group (1.79 < 3.25, p value = 0.0043). In conclusion, our trial confirms RFA and
MWA are both excellent choices in terms of efficacy and safety in lung tumour
treatments. However, when compared to RFA therapy, MWA produced a less
intraprocedural pain and a significant reduction in tumour mass.
PMID- 28417357
TI - Quantitative Kinetic Characterization of Glycoside Hydrolases Using High
Performance Anion-Exchange Chromatography (HPAEC).
AB - High-performance anion-exchange chromatography coupled to pulsed amperometric
detection (HPAEC-PAD) is a powerful analytical technique enabling the high
resolution separation and sensitive quantification of oligosaccharides. Here, we
describe a general method for the determination of glycoside hydrolase kinetics
that harnesses the intrinsic power of HPAEC-PAD to simultaneously monitor the
release of multiple products under conditions of low substrate conversion. Thus,
the ability to track product release under initial-rate conditions with substrate
concentrations as low as 5 MUM enables the determination of Michaelis-Menten
kinetics for glycosidase activities, including hydrolysis and transglycosylation.
This technique may also be readily extended to other carbohydrate-active enzymes
(CAZymes), including polysaccharide lyases, and glycosyl transferases.
PMID- 28417358
TI - Measuring Enzyme Kinetics of Glycoside Hydrolases Using the 3,5-Dinitrosalicylic
Acid Assay.
AB - Use of the 3,5-dinitrosalicylic acid reagent allows the simple and rapid
quantification of reducing sugars. The method can be used for analysis of
biological samples or in the characterization of enzyme reactions. Presented here
is an application of the method in measuring the kinetics of a glycoside
hydrolase reaction, including the optimization of the DNSA reagent, and the
production of a standard curve of absorbance and sugar concentration.
PMID- 28417359
TI - An Improved Kinetic Assay for the Characterization of Metal-Dependent Pectate
Lyases.
AB - Pectate lyases are a subset of polysaccharide lyases (PLs) that specifically
utilize a metal dependent beta-elimination mechanism to cleave glyosidic bonds in
homogalacturonan (HG; alpha-D-1,4-galacturonic acid). Most commonly, PLs harness
calcium for catalysis; however, some PL families (e.g., PL2 and PL22) display
preferences for transitional metals. Deploying alternative metals during beta
elimination is correlated with signature coordination pocket chemistry, and is
reflective of the evolution, functional specialization, and cellular location of
PL activity. Here we describe an optimized method for the analysis of metal
dependent polysaccharide lyases (PLs). We use an endolytic PL2 from Yersinia
enterocolitica (YePL2A) as example to demonstrate how altering the catalytic
metal within the reaction can modulate PL kinetics.
PMID- 28417360
TI - Colorimetric Detection of Acetyl Xylan Esterase Activities.
AB - Colorimetric detection of reaction products is typically preferred for initial
surveys of acetyl xylan esterase (AcXE) activity. This chapter will describe
common colorimetric methods, and variations thereof, for measuring AcXE
activities on commercial, synthesized, and natural substrates. Whereas assays
using pNP-acetate, alpha-naphthyl acetate, and 4-methylumbelliferyl acetate
(4MUA) are emphasized, common methods used to measure AcXE activity towards
carbohydrate analogs (e.g., acetylated p-nitrophenyl beta-D-xylopyranosides) and
various acetylated xylans are also described. Strengths and limitations of the
colorimetric assays are highlighted.
PMID- 28417361
TI - Methods for Determining Glycosyltransferase Kinetics.
AB - Glycosyltransferases are a class of biosynthetic enzymes that transfer individual
activated monosaccharide units to specific acceptors. Colorimetric assays using
the detection of released products such as para-nitrophenol and coupled assays
for inorganic phosphate detection allow for convenient and quantifiable kinetic
characterization. These techniques may be applied to determine the enzymatic
activity of glycosyltransferases by indirectly measuring the transfer of
nucleotide-activated donor carbohydrate units to various cognate acceptor
molecules. In addition to an overview of these methods, the protocol for
quantifying the glycosyltransferase activity used for the characterization of
penicillin-binding proteins (PBPs) involving the transfer of lipid II to form
elongated murein chains during bacterial cell wall synthesis is described herein.
PMID- 28417362
TI - Analyzing Activities of Lytic Polysaccharide Monooxygenases by Liquid
Chromatography and Mass Spectrometry.
AB - Lytic polysaccharide monooxygenases perform oxidative cleavage of glycosidic
bonds in various polysaccharides. The majority of LMPOs studied so far possess
activity on either cellulose or chitin and analysis of these activities is
therefore the main focus of this review. Notably, however, the number of LPMOs
that are active on other polysaccharides is increasing. The products generated by
LPMOs from cellulose are either oxidized in the downstream end (at C1) or
upstream end (at C4), or at both ends. These modifications only result in small
structural changes, which makes both chromatographic separation and product
identification by mass spectrometry challenging. The changes in physicochemical
properties that are associated with oxidation need to be considered when choosing
analytical approaches. C1 oxidation leads to a sugar that is no longer reducing
but instead has an acidic functionality, whereas C4 oxidation leads to products
that are inherently labile at high and low pH and that exist in a keto-gemdiol
equilibrium that is strongly shifted toward the gemdiol in aqueous solutions.
Partial degradation of C4-oxidized products leads to the formation of native
products, which could explain why some authors claim to have observed glycoside
hydrolase activity for LPMOs. Notably, apparent glycoside hydrolase activity may
also be due to small amounts of contaminating glycoside hydrolases since these
normally have much higher catalytic rates than LPMOs. The low catalytic turnover
rates of LPMOs necessitate the use of sensitive product detection methods, which
limits the analytical possibilities considerably. Modern liquid chromatography
and mass spectrometry have become essential tools for evaluating LPMO activity,
and this chapter provides an overview of available methods together with a few
novel tools. The methods described constitute a suite of techniques for analyzing
oxidized carbohydrate products, which can be applied to LPMOs as well as other
carbohydrate-active redox enzymes.
PMID- 28417363
TI - Carbohydrate Depolymerization by Intricate Cellulosomal Systems.
AB - Cellulosomes are multi-enzymatic nanomachines that have been fine-tuned through
evolution to efficiently deconstruct plant biomass. Integration of cellulosomal
components occurs via highly ordered protein-protein interactions between the
various enzyme-borne dockerin modules and the multiple copies of the cohesin
modules located on the scaffoldin subunit. Recently, designer cellulosome
technology has been established to provide insights into the architectural role
of catalytic (enzymatic) and structural (scaffoldin) cellulosomal constituents
for the efficient degradation of plant cell wall polysaccharides. Owing to
advances in genomics and proteomics, highly structured cellulosome complexes have
recently been unraveled, and the information gained has inspired the development
of designer cellulosome technology to new levels of complex organization. These
higher-order designer cellulosomes have in turn fostered our capacity to enhance
the catalytic potential of artificial cellulolytic complexes. In this chapter,
methods to produce and employ such intricate cellulosomal complexes are reported.
PMID- 28417364
TI - Affinity Electrophoresis for Analysis of Catalytic Module-Carbohydrate
Interactions.
AB - Affinity electrophoresis has long been used to study the interaction between
proteins and large soluble ligands. The technique has been found to have great
utility for the examination of polysaccharide binding by proteins, particularly
carbohydrate binding modules (CBMs). In recent years, carbohydrate surface
binding sites of proteins mostly enzymes have also been investigated by this
method. Here, we describe a protocol for identifying binding interactions between
enzyme catalytic modules and a variety of carbohydrate ligands.
PMID- 28417365
TI - Quantifying CBM Carbohydrate Interactions Using Microscale Thermophoresis.
AB - MicroScale Thermophoresis (MST) is an emerging technology for studying a broad
range of biomolecular interactions with high sensitivity. The affinity constant
can be obtained for a wide range of molecules within minutes based on reactions
in microliters. Here, we describe the application of MST in quantifying two CBM
carbohydrate interactions, a CBM3a toward cellulose nanocrystals and a CBM4
against xylohexaose.
PMID- 28417366
TI - Characterization of Protein-Carbohydrate Interactions by NMR Spectroscopy.
AB - Solution-state nuclear magnetic resonance (NMR) spectroscopy can be used to
monitor protein-carbohydrate interactions. Two-dimensional 1H-15N heteronuclear
single quantum coherence (HSQC)-based techniques described in this chapter can be
used quickly and effectively to screen a set of possible carbohydrate binding
partners, to quantify the dissociation constant (K d) of any identified
interactions, and to map the carbohydrate binding site on the structure of the
protein. Here, we describe the titration of a family 32 carbohydrate binding
module from Clostridium perfringens (CpCBM32) with the monosaccharide N
acetylgalactosamine (GalNAc), in which we calculate the apparent dissociation of
the interaction, and map the GalNAc binding site onto the structure of CpCBM32.
PMID- 28417367
TI - Measuring the Biomechanical Loosening Action of Bacterial Expansins on Paper and
Plant Cell Walls.
AB - Expansins are proteins that loosen plant cell walls but lack enzymatic activity.
Here, we describe two protocols tailored to measure the biomechanical activity of
bacterial expansin. The first assay relies on weakening of filter paper by
expansin. The second assay is based on induction of creep (long-term,
irreversible extension) of plant cell wall samples.
PMID- 28417368
TI - Bioinspired Assemblies of Plant Cell Walls for Measuring Protein-Carbohydrate
Interactions by FRAP.
AB - The interactions of proteins involved in plant cell wall hydrolysis, such as
enzymes and CBMs, significantly determine their role and efficiency. In order to
go beyond the characterization of interactions with simple ligands, bioinspired
assemblies combined with the measurement of diffusion and interaction by FRAP
offer a relevant alternative for highlighting the importance of different
parameters related to the protein affinity and to the assembly.
PMID- 28417369
TI - CBMs as Probes to Explore Plant Cell Wall Heterogeneity Using
Immunocytochemistry.
AB - Immunocytochemistry is a widely used technique to localize antigen within intact
tissues. Plant cell walls are complex matrixes of highly decorated
polysaccharides and the large number of CBM families displaying specific
substrate recognition reflects this complexity. The accessibility of large
proteins, such as antibodies, to their cell wall epitopes may be sometimes
difficult due to steric hindrance problems. Due to their smaller size, CBMs are
interesting alternative probes. The aim of this chapter is to describe the use of
CBM as probes to explore complex polysaccharide topochemistry in muro and to
quantify enzymatic deconstruction.
PMID- 28417370
TI - Determining the Localization of Carbohydrate Active Enzymes Within Gram-Negative
Bacteria.
AB - Investigating the subcellular location of secreted proteins is valuable for
illuminating their biological function. Although several bioinformatics programs
currently exist to predict the destination of a trafficked protein using its
signal peptide sequence, these programs have limited accuracy and often require
experimental validation. Here, we present a systematic method to fractionate gram
negative cells and characterize the subcellular localization of secreted
carbohydrate active enzymes (CAZymes). This method involves four parallel
approaches that reveal the relative abundance of protein within the cytoplasm,
periplasm, outer membrane, and extracellular environment. Cytoplasmic and
periplasmic proteins are fractionated by lysis and osmotic shock, respectively.
Outer membrane bound proteins are determined by comparing cells before and after
exoproteolytic digestion. Extracellularly secreted proteins are collected from
the media and concentrated. These four different fractionations can then be
probed for the presence and quantity of target proteins using immunochemical
methods such as Western blots and ELISAs, or enzyme activity assays.
PMID- 28417371
TI - Analysis of Complex Carbohydrate Composition in Plant Cell Wall Using Fourier
Transformed Mid-Infrared Spectroscopy (FT-IR).
AB - Fourier transformed mid-infrared spectroscopy (FTIR) is a powerful tool for
compositional analysis of plant cell walls (Acebes et al., Front Plant Sci 5:303,
2014; Badhan et al., Biotechnol Biofuels 7:1-15, 2014; Badhan et al., BioMed Res
Int 2015: 562952, 2015; Roach et al., Plant Physiol 156:1351-1363, 2011). The
infrared spectrum generates a fingerprint of a sample with absorption peaks
corresponding to the frequency of vibrations between the bonds of the atoms
making up the material. Here, we describe a method focused on the use of FTIR in
combination with principal component analysis (PCA) to characterize the
composition of the plant cell wall. This method has been successfully used to
study complex enzyme saccharification processes like rumen digestion to identify
recalcitrant moieties in low-quality forage which resist rumen digestion (Badhan
et al., BioMed Res Int 2015: 562952, 2015), as well as to characterize cell wall
mutant lines or transgenic lines expressing exogenous hydrolases (Badhan et al.,
Biotechnol Biofuels 7:1-15, 2014; Roach et al., Plant Physiol 156:1351-1363,
2011). The FTIR method described here facilitates high-throughput identification
of the major compositional differences across a large set of samples in a low
cost and nondestructive manner.
PMID- 28417372
TI - Separation and Visualization of Glycans by Fluorophore-Assisted Carbohydrate
Electrophoresis.
AB - Fluorophore-assisted carbohydrate electrophoresis (FACE) is a method in which a
fluorophore is covalently attached to the reducing end of carbohydrates, thereby
allowing visualization following high-resolution separation by electrophoresis.
This method can be used for carbohydrate profiling and sequencing, as well as for
the determination of the specificity of carbohydrate-active enzymes. Here, we
describe and demonstrate the use of FACE to separate and visualize the glycans
released following digestion of oligosaccharides by glycoside hydrolases (GHs)
using two examples: (1) the digestion of chitobiose by the streptococcal beta
hexosaminidase GH20C, and (2) the digestion of glycogen by the GH13 member SpuA.
PMID- 28417374
TI - Probing the Complex Architecture of Multimodular Carbohydrate-Active Enzymes
Using a Combination of Small Angle X-Ray Scattering and X-Ray Crystallography.
AB - The various modules in multimodular carbohydrate-active enzymes (CAZymes) may
function in catalysis, carbohydrate binding, protein-protein interactions or as
linkers. Here, we describe how combining the biophysical techniques of Small
Angle X-ray Scattering (SAXS) and macromolecular X-ray crystallography (XRC)
provides a powerful tool for examination into questions related to overall
structural organization of ultra multimodular CAZymes.
PMID- 28417373
TI - A Rapid Procedure for the Purification of 8-Aminopyrene Trisulfonate (APTS)
Labeled Glycans for Capillary Electrophoresis (CE)-Based Enzyme Assays.
AB - Purified glycan standards are required for glycan arrays, characterizing
substrate specificities of glycan-active enzymes, and to serve as retention-time
or mobility standards for various separation techniques. This chapter describes a
method for the rapid separation, and subsequent desalting, of glycans labeled
with the highly fluorescent fluorophore 8-aminopyrene 1,3,6-trisulfonate (APTS).
By using fluorophore-assisted carbohydrate electrophoresis (FACE) on
polyacrylamide gels, which utilizes equipment readily available in most molecular
biology laboratories, many APTS-labeled glycans can be simultaneously resolved.
Excising specific gel bands containing the desired APTS-labeled glycans, followed
by glycan elution from the gel and subsequent solid-phase extraction (SPE),
yields single glycan species free of excess labeling reagents and buffer
components. This chapter describes a FACE/SPE procedure ideal for preparing
glycans for capillary electrophoresis (CE)-based enzyme assays, as well as for
the purification of rare, commercially unavailable glycans from tissue culture
samples.
PMID- 28417375
TI - Metagenomics and CAZyme Discovery.
AB - Microorganisms play a primary role in regulating biogeochemical cycles and are a
valuable source of enzymes that have biotechnological applications, such as
carbohydrate-active enzymes (CAZymes). However, the inability to culture the
majority of microorganisms that exist in natural ecosystems using common culture
dependent techniques restricts access to potentially novel cellulolytic bacteria
and beneficial enzymes. The development of molecular-based culture-independent
methods such as metagenomics enables researchers to study microbial communities
directly from environmental samples, and presents a platform from which enzymes
of interest can be sourced. We outline key methodological stages that are
required as well as describe specific protocols that are currently used for
metagenomic projects dedicated to CAZyme discovery.
PMID- 28417376
TI - Identification of Genes Involved in the Degradation of Lignocellulose Using
Comparative Transcriptomics.
AB - Lignocellulosic biomass represents an abundant, renewable resource that can be
used to produce biofuels, low-cost livestock feed, and high-value chemicals. The
potential of this resource has led to intensive research efforts to develop cost
effective methods to breakdown lignocellulose. The efficiency with which the
anaerobic fungi (phylum Neocallimastigomycota) degrade plant biomass is well
recognized and in recent years has received renewed interest. Transcriptomics has
been used to identify enzymes that are expressed by these fungi and are involved
in the degradation of a range of lignocellulose feedstocks. The transcriptome is
the entire complement of coding and noncoding RNA transcripts that are expressed
by a cell under a particular set of conditions. Monitoring changes in gene
expression can provide fundamental information about the biology of an organism.
Here we outline a general methodology that will enable researchers to conduct
comparative transcriptomic studies with the goal of identifying enzymes involved
in the degradation of the plant cell wall. The method described here includes
growth of fungal cultures, isolation and sequencing of RNA, and a basic
description of data analysis for bioinformatic identification of differentially
expressed transcripts.
PMID- 28417377
TI - Isolation and Preparation of Extracellular Proteins from Lignocellulose Degrading
Fungi for Comparative Proteomic Studies Using Mass Spectrometry.
AB - Fungi utilize a unique mechanism of nutrient acquisition involving extracellular
digestion. To understand the biology of these microbes, it is important to
identify and characterize the function of proteins that are secreted and involved
in this process. Mass spectrometry-based proteomics is a powerful tool to study
complex mixtures of proteins and understand how the proteins produced by an
organism change in response to different conditions. Many fungi are efficient
decomposers of plant cell wall, and anaerobic fungi are well recognized for their
ability to digest lignocellulose. Here, we outline a protocol for the enrichment
and isolation of proteins secreted by anaerobic fungi after growth on simple
(glucose) and complex (straw and alfalfa hay) carbon sources. We provide detailed
instruction on generating protein fragments and preparing these for proteomic
analysis using reversed phase chromatography and mass spectrometry.
PMID- 28417378
TI - ?
PMID- 28417379
TI - ?
PMID- 28417380
TI - ?
PMID- 28417381
TI - [Hypertension in elderly over 80 - benefit and harm of antihypertensive
treatment].
PMID- 28417382
TI - ?
PMID- 28417383
TI - [Scabies].
PMID- 28417384
TI - [Pediculosis capitis - an update].
PMID- 28417385
TI - ?
PMID- 28417386
TI - ?
PMID- 28417387
TI - ?
PMID- 28417388
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PMID- 28417389
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PMID- 28417390
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PMID- 28417392
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PMID- 28417391
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PMID- 28417393
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PMID- 28417394
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PMID- 28417395
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PMID- 28417397
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PMID- 28417396
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PMID- 28417398
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PMID- 28417399
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PMID- 28417400
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PMID- 28417401
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PMID- 28417402
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PMID- 28417403
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PMID- 28417404
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PMID- 28417405
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PMID- 28417406
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PMID- 28417407
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PMID- 28417408
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PMID- 28417409
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PMID- 28417410
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PMID- 28417411
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PMID- 28417412
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PMID- 28417413
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PMID- 28417414
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PMID- 28417416
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PMID- 28417417
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PMID- 28417419
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PMID- 28417418
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PMID- 28417420
TI - [Current treatment of dyspepsia in primary care].
PMID- 28417422
TI - Selection of an Artificial Diet for Laboratory Rearing of Opogona sacchari
(Lepidoptera: Tineidae) (Bojer, 1856).
AB - The banana moth Opogona sacchari (Bojer) (Lepidoptera: Tineidae) is a polyphagous
pest that can cause serious damage, in particular to banana crops in southern
Brazil. The insect is a quarantine pest in several countries, including
Argentina, the main consumer market for bananas from southern Brazil. Little
information is available about the biology and ecology of this moth, such as a
suitable diet for laboratory rearing. In order to provide support for integrated
pest management of the pest, this study furnished data for selecting two diets
suitable for continuous laboratory rearing of O. sacchari, one based on dried
beans, wheat germ, soy bran, brewer's yeast, and casein and another diet with
wheat germ and casein as protein sources. With both diets, the viability of the
egg-adult period exceeded 68%, with fertility over 338 eggs per female. A
corrected biotic potential analysis gave similar values for the two diets.
PMID- 28417421
TI - A review of infectious complications after haploidentical hematopoietic stem cell
transplantations.
AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation from
haploidentical donor is a feasible option for patients with hematological
diseases who lack a suitable HLA-matched donor, but viral and fungal infections
are still the most common causes of morbidity and mortality in haploidentical
transplantation setting because of delayed immune reconstitution, increased risk
of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review
will focus on the infectious complications after haploidentical hematopoietic
stem cell transplantation (HSCT). MATERIALS AND METHODS: Electronic publications
were searched until February 2017 throughout databases, including Pubmed,
Cochrane, and Embase. The following keywords were used 'haploidentical
transplantation', 'infection', 'T cell replete', and 'T cell deplete'. RESULTS:
An increased incidence of bacterial, fungal, or viral infections is detected in
haplo-HSCT compared to related, unrelated, or cord blood transplantations.
Neutropenia and use of systemic steroid for GvHD and delayed immune
reconstitution are important risk factors for infection after haplo-HSCT.
CONCLUSION: A shift towards T cell repletes haplo-HSCT with post-transplant
cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the
incidence of viral and fungal infections is detected to be lower. Prophylaxis and
pre-emptive treatment strategies should be applied according to patient status.
PMID- 28417423
TI - Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of
Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected
with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the
Study of Alzheimer's Disease Pathology.
AB - Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models
in neurodegenerative research, and their use has advanced the understanding of
the pathology of neurodegeneration over the past few decades. In Alzheimer's
disease (AD), several pathogenic mutations have been described, all of which
cause elevated levels of pathological hallmarks such as amyloid-beta (Abeta).
Although the genetics of Alzheimer's disease is well known, familial AD only
accounts for a small number of cases in the population, with the rest being
sporadic AD, which contains no known mutations. Currently, most of the in vitro
models used to study AD pathogenesis only examine the level of Abeta42 as a
confirmation of successful model generation and only perform comparisons between
wild-type APP and single mutants of the APP gene. Recent findings have shown that
the Abeta42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic
indicator for AD patients than is Abeta42 alone and that more extensive Abeta
formation, such as accumulation of intraneuronal Abeta, Abeta plaques, soluble
oligomeric Abeta (oAbeta), and insoluble fibrillar Abeta (fAbeta) occurs in
TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later
leading to greater progressive impairment of the brain. In this study, we
generated SH-SY5Y cells stably transfected separately with wild-type APP, the
Swedish mutation of APP, and the Swedish and Indiana mutations of APP and
evaluated the APP expression as well as the Abeta42/40 ratio in those cells. The
double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP
protein and showed a high Abeta2/40 ratio compared to wild-type and single-mutant
cells.
PMID- 28417424
TI - A Review of the Anaerobic Digestion of Fruit and Vegetable Waste.
AB - Fruit and vegetable waste is an ever-growing global question. Anaerobic digestion
techniques have been developed that facilitate turning such waste into possible
sources for energy and fertilizer, simultaneously helping to reduce environmental
pollution. However, various problems are encountered in applying these
techniques. The purpose of this study is to review local and overseas studies,
which focus on the use of anaerobic digestion to dispose fruit and vegetable
wastes, discuss the acidification problems and solutions in applying anaerobic
digestion for fruit and vegetable wastes and investigate the reactor design
(comparing single phase with two phase) and the thermal pre-treatment for
processing raw wastes. Furthermore, it analyses the dominant microorganisms
involved at different stages of digestion and suggests a focus for future
studies.
PMID- 28417425
TI - Overexpression of OsHSP18.0-CI Enhances Resistance to Bacterial Leaf Streak in
Rice.
AB - BACKGROUND: The small heat shock proteins represent a large family of proteins
that respond to a wide range of abiotic and biotic stresses. OsHsp18.0-CI confers
tolerance to salt and cadmium and interacts with viral RNA-dependent RNA
polymerase (RdRp). However, the direct function of OsHsp18.0-CI in resistance
against biotic stresses remains unclear in rice. RESULTS: Here, we report that
the expression of OsHsp18.0-CI was up-regulated upon inoculation with RS105, a
strain of Xanthomonas oryzae pv. oryzicola (Xoc) that causes bacterial leaf
streak in rice. In comparison with wild-type, OsHsp18.0-CI overexpression (OE)
lines exhibited enhanced resistance to RS105, whereas repression lines exhibited
compromised resistance to RS105. In addition, the transcriptional profiles of
wild type and OE lines were compared with and without inoculation with RS105.
After inoculation with RS105, most of the genes with up-regulated expression were
commonly stimulated in the wild type and OE lines, with stronger induction in the
OE lines than in wild type. CONCLUSION: Our study reveals that OsHsp18.0-CI
positively regulates resistance to Xoc by mediating an enhanced version of the
basal defense response in rice.
PMID- 28417426
TI - Telehealth delivery of the diabetes prevention program to rural communities.
AB - The Centers for Disease Control and Prevention, State and Local Health
Departments, and other organizations in the USA are working to increase
population access to the Diabetes Prevention Program (DPP) lifestyle
intervention. Delivering the DPP through telehealth videoconference may increase
access to this intervention, particularly in rural communities. The purpose of
this study was to compare participation, monitoring of diet and physical
activity, and weight loss in participants receiving the intervention on-site and
those participating virtually through telehealth. Beginning in 2008, Holy Rosary
Healthcare collaborated with the Montana Department of Public Health and Human
Services to provide the DPP to participants on-site in one community and
simultaneously through telehealth to participants in multiple other communities.
From 2008 through 2015, 894 participants were enrolled in the program (29% at
telehealth sites). The mean age of participants was 51.7 years and 84% were
female. Overall, participants attended 14.4, 3.9, and 15.0 weekly core, post
core, and total sessions, respectively. There were no statistically significant
differences in number of intervention sessions attended by the telehealth or on
site participants. There were no statistically significant differences in the
mean weight loss or reduction in BMI between the telehealth and the on-site
groups. There also were no statistically significant differences in the
percentage of telehealth or on-site participants who achieved >=5% weight loss
(56 vs. 57%) or the 7% weight loss goal (38 vs. 41%). Our findings suggest that
participants receiving the DPP through telehealth have similar rates of
participation and achieve similar weight loss as participants attending the
program on-site.
PMID- 28417427
TI - Extraperitoneal Robot-Assisted Radical Prostatectomy: Indications, Technique and
Outcomes.
AB - PURPOSE OF REVIEW: Extraperitoneal robot-assisted radical prostatectomy (eRARP)
is an alternative to the more commonly employed transperitoneal RARP (tRARP) for
treatment of clinically localized prostate cancer. The purpose of this review is
to discuss indications in which eRARP would be a more favorable approach in
comparison to tRARP. In addition, we will discuss the safety and technique of
eRARP. RECENT FINDINGS: Recently published work has highlighted the outcomes and
safety of eRARP in comparison to tRARP; specifically that eRARP is not inferior
to tRARP. In addition, eRARP may be preferred in certain circumstances. For
example, Ludwig et al. recently discussed the concomitant repair of inguinal
hernia during eRARP. Extraperitoneal RARP is a safe and effective alternative to
tRARP. With previous knowledge and experience with tRARP, urologists can adapt
the extraperitoneal approach without difficulty. This approach is useful for
specific situations in which tRARP may be challenging.
PMID- 28417428
TI - Outcomes of Minimally Invasive Inguinal Hernia Repair at the Time of Robotic
Radical Prostatectomy.
AB - Abdominal straining associated with voiding dysfunction or constipation has
traditionally been associated with the development of abdominal wall hernias.
Thus, classic general surgery dictum recommends that any coexistent bladder
outlet obstruction should be addressed by the urologist before patients undergo
surgical repair of a hernia. While organ-confined prostate cancer is usually not
associated with the development of lower urinary tract symptoms, a modest
proportion of patients treated with radical prostatectomy may have coexisting
benign prostatic hyperplasia with elevated symptom scores and hernias may be
incidentally detected at the time of surgery. Furthermore, dissection of the
space of Retzius during retropubic or minimally invasive prostatectomy may result
exposure of abdominal wall defects which may have been present, but asymptomatic
if plugged with preperitoneal fat. Herein we examine the literature regarding the
incidence of postoperative inguinal hernias after prostatectomy, review potential
risk factors which could aid in preoperative patient identification, and discuss
the published experience regarding concurrent hernia repair at the time of open
or minimally invasive radical prostatectomy.
PMID- 28417429
TI - Approach to Androgen Deprivation in the Prostate Cancer Patient with Pre-existing
Cardiovascular Disease.
AB - PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) is a mainstay of treatment
for advanced prostate cancer. Several studies have reported an association
between ADT and an increase in cardiovascular events, especially in those
receiving gonadotropin-releasing hormone (GnRH) agonists compared to GnRH
antagonists. We review the body of literature reporting the association of ADT
and cardiovascular morbidity, and discuss the proposed mechanism of
cardiovascular disease due to ADT including metabolic changes that may promote
atherosclerosis and local hormonal effects that may increase plaque rupture and
thrombosis. RECENT FINDINGS: GnRH agonists appear to increase the risk of
cardiovascular morbidity by 20-25% in men on these agents compared those who do
not receive ADT. GnRH antagonists may appear to have halve this risk while
improving PSA progression-free survival. GnRH antagonists may be superior to GnRH
agonists for patients with significant cardiovascular disease, significant
metastatic disease burden, or severe lower urinary tract symptoms.
PMID- 28417430
TI - The Emergence of Kidney Stone Disease During Childhood-Impact on Adults.
AB - PURPOSE OF REVIEW: The goal of this chapter is to review the recent epidemiologic
trends of kidney stone disease and discuss the impact of the increasing incidence
of nephrolithiasis among children on adults with respect to extra-renal
manifestations, surgical management, and secondary prevention. RECENT FINDINGS:
Among pediatric patients, kidney stone disease has been increasing at a rate of
approximately 5-10% annually. Kidney stone disease has been associated with
increased risks of coronary heart disease, chronic kidney disease, hypertension,
and decreased bone mineral density, which is concerning for patients diagnosed at
a young age. Improvements in endo-urology have allowed for less invasive surgical
treatment of stones in the pediatric population. However, current guidelines
often lack recommendations for evaluation, medical, and surgical management of
children with kidney stone disease. Nephrolithiasis is a disorder of mineral
metabolism, which is beginning during childhood with increasing frequency. Kidney
stone disease often exists over the lifetime and is associated with serious
conditions that are important for pediatric and adult urologists to recognize and
consider in their evaluation and treatment of patients.
PMID- 28417431
TI - Robotic Kidney Transplantation-an Update.
AB - PURPOSE OF REVIEW: Over the last decade, there have been advances in kidney
transplantation with introduction of minimally invasive surgery. Robotic surgery
is becoming increasingly common across the specialities. There is now increasing
experience in robotic kidney transplantation, though it remains a niche
procedure. Initial reports suggest that this is a safe, feasible operation when
performed by teams familiar with robotic surgery. There have been a few
modifications to the initially described procedure, as a result of increasing
experience. RECENT FINDINGS: There is no significant difference in graft and
patient survival when compared with open surgery and laparoscopic kidney
transplantation. It is a safe procedure and therefore represents a viable
alternative to open surgery in selected patients particularly the obese. The
advantages include less postoperative pain and fewer wound complications such as
surgical site infections and hernia, which could be particularly advantageous in
the obese. Robotic kidney transplantation is procedure that has been developed
over the last decade and could have applicability in kidney transplantation in
the obese. Its main benefit is in enabling surgery in less accessible spaces due
to body habitus, combined with those of using a smaller incision with less
associated morbidity, with no inferiority in the reported primary outcomes of
graft and patient survival. There are capital costs associated with this
procedure, but further studies on the cost-effectiveness of robotic kidney
transplantation are needed before it can be adopted widely.
PMID- 28417432
TI - Evaluating Community Measures of Healthy Food Access.
AB - Several community level measures of healthy food access exist, but evaluation
efforts have been limited leaving uncertainty about how to prioritize communities
for intervention. This study aimed to assess several existing measures to inform
statewide public health planning efforts in New Jersey, USA. We assessed
agreement between community measures of healthy food access and then evaluated
the predictive validity of each measure by describing its association with
complete fruit and vegetable cash-value voucher redemption (proportion redeemed
>=70, >=80, >=90%) among 30,078 low-income households participating in the New
Jersey Special Supplemental Nutrition Program for Women, Infants, and Children
(WIC) during 2013-2014. The United States Department of Agriculture's (USDA) food
desert measure agreed with the Centers for Disease Control and Prevention's (CDC)
no healthier food retailers (NHFR) measure for 76.5% of New Jersey census tracts,
but the Kappa statistic was only 0.10. For urban households, the NHFR measure was
negatively associated with complete redemption after adjusting for demographic
factors and Supplemental Nutrition Assistance Program participation (>=70% odds
ratio (OR) 0.68, 95% confidence interval (CI) 0.61-0.75; >=80% OR 0.67, 95% CI
0.62-0.73; >=90% OR 0.72, 95% CI 0.66-0.77). For rural households, a negative
association was observed for the USDA's low-income/low-vehicle access measure
(>=70% OR 0.48, 95% CI 0.26-0.90). The CDC's NHFR measure is more appropriate for
prioritizing urban areas while the USDA's low-income/low-vehicle access measure
may be better for rural areas.
PMID- 28417433
TI - Investigating Responses to Food Insecurity Among HIV Positive People in Resource
Rich Settings: A Systematic Review.
AB - Many of the 36.7 million people living with HIV are also assumed to be food
insecure. The implications of food insecurity in people living with HIV are
significant, with food insecurity associated with an increased likelihood of
tobacco, alcohol, and illicit drug use, experiences of depression or depressive
symptoms, poor adherence and delayed uptake of HIV medication, nutritional
vulnerability leading to interference of medication, and the uptake of risky
behaviours as a way to gain access to food resources. This review sought to
present the current intervention research around the experiences of food
insecurity in PLWHA in high resource countries to determine successful models to
address the issue. Only five articles were identified in a systematic search,
three reported on studies that were conducted in the USA and two in Canada. Two
articles were cross sectional, one was a program evaluation, one ethnography, and
one took a qualitative approach. This review highlights a lack of published
research in the area of HIV and food insecurity in resource rich countries. The
findings of this study suggest that there are currently no standard or best
practice ways to provide food aid to PLWHA to reduce food security. The lack of
published results means that while there may be good programs operating in the
community, this information and knowledge is not being shared, resulting in a
lack of consistency in approach, possible duplication, and the potential for
wasted resources. Overall, this review suggests a need for more dedicated
evaluation and longitudinal research.
PMID- 28417434
TI - Characterizing Rural Food Access in Remote Areas.
AB - Residents of rural areas may have limited access to healthy foods, leading to
higher incidence of diet related health issues. Smaller grocers in rural areas
experience challenges in maintaining fresh produce and other healthy foods
available for customers. This study assessed the rural food environment in
northeast Lower Michigan in order to inform healthy food financing projects such
as the Michigan Good Food Fund. The area's retail food businesses were
categorized using secondary licensing, business, and nutrition program databases.
Twenty of these stores were visited in person to verify the validity of the
categories created, and to assess the availability of healthy foods in their
aisles. In-depth interviews with key informants were carried out with store
owners, economic development personnel, and other food system stakeholders having
knowledge about food access, in order to learn more about the specific challenges
that the area faces. Out-shopping, seasonality, and economic challenges were
found to affect healthy food availability. Mid-sized independent stores were
generally found to have a larger selection of healthy foods, but smaller rural
groceries also have potential to provide fresh produce and increase food access.
Potential healthy food financing projects are described and areas in need of
further research are identified.
PMID- 28417435
TI - Lachnospiraceae shift in the microbial community of mice faecal sample effects on
water immersion restraint stress.
AB - Stress, including both psychological and physical stimulation, can cause changes
in the microbiota and mucosal function of the gastrointestinal system. There are
few research studies available about the faecal microbiota changes after stress,
such as water immersion restraint stress (WIRS). Therefore, in this study, we
focused on analysing the composition changes of faecal microbiota in WIRS mice.
The WIRS model, in which Blab/c mice were immersed in 21 +/- 2 degrees C water
for 4 h each day for 14 days, was established. Behavioural changes, the serum
levels of corticosterone, IFN-gamma and IL-17 and gastric mucosal injury were
also assessed. Ten faecal microbiota samples were detected by Illumina Miseq
sequencing of the 16S rRNA genes from 367205 characterised sequences. Finally, we
find significant differences in the faecal microbiota composition between the
control and the WIRS groups. There was an obvious increase in Lachnospiraceae in
the WIRS mice (p = 0.0286, p < 0.05), which is associated with human diseases,
such as ulcerative colitis, Crohn's and celiac disease. Our research indicates
that stress changes in the faecal microbiota. These results suggest that
observing shifts of the intestinal microbiota is a promising method to explore
the mechanism of the stress associated with gastrointestinal diseases and to
provide us with a better understanding of the relationship between the microbiota
and disease.
PMID- 28417436
TI - Evaluation of the Pharmacokinetics and Pharmacodynamics of Prasugrel in Japanese
Elderly Subjects.
AB - BACKGROUND AND OBJECTIVE: An increased incidence in bleeding events has been
reported in Western elderly patients receiving prasugrel. Therefore, doses in
Japanese elderly subjects need to be carefully determined. We assessed the
pharmacokinetic and pharmacodynamic effects of prasugrel at the clinical dose
used in Japan in healthy Japanese elderly subjects compared with non-elderly
subjects. METHODS: In an open-label parallel-group study conducted in Japan, two
groups (elderly, aged >75 years; non-elderly, aged 45-65 years) received a 20-mg
loading dose and a 3.75-mg maintenance dose of prasugrel for 7 days. Plasma
concentration of its active metabolite, R-138727, and pharmacokinetic parameters
were determined on days 1 and 7 after dosing. Pharmacodynamic response to 20 uM
of adenosine diphosphate-induced platelet aggregation was measured by light
transmission aggregometry. RESULTS: A total of 47 subjects were enrolled (23
elderly, 24 non-elderly). There was no statistically significant difference in
pharmacokinetic parameters between groups: area under the plasma concentration
time curve up to the last quantifiable time and maximum plasma concentration were
about 174-175 ng.h/mL and 134-153 ng/mL, respectively, after the loading dose;
and about 25-26 ng.h/mL and 25 ng/mL, respectively, after the maintenance dose.
Inhibition of platelet aggregation was higher in the elderly subjects than in the
non-elderly subjects, with a statistically significant difference from 24 h after
the loading dose. No serious adverse events (bleeding or non-bleeding) occurred.
CONCLUSIONS: Prasugrel (20-mg loading dose; 3.75-mg maintenance dose) produced a
slight increase in antiplatelet efficacy in elderly compared with non-elderly
subjects, despite no statistically significant difference in the
pharmacokinetics.
PMID- 28417437
TI - Cumulative Impact of Stressful Life Events on the Development of Takotsubo
Cardiomyopathy.
AB - BACKGROUND: The role of stressful life events in the onset of Takotsubo
cardiomyopathy (TC) is unclear. PURPOSE: This study sought to examine
associations between type, timing, and number of stressful life events and onset
of TC. METHODS: A case-control study conducted among consecutive incident female
TC cases and myocardial infarction (MI) controls admitted to two emergency
departments in New England. Healthy female controls (HC) were recruited from a
volunteers' registry. Information about the timing, type, and number of triggers
during the 6 months preceding hospitalization was systematically collected using
the PERI Life Events Scale about 1 month post-discharge. Group differences were
evaluated using ANOVA, chi-square, and Kruskal-Wallis statistics. Generalized
linear models were used to adjust for confounding variables. RESULTS: Between
March 2013 and October 2015, 107 women were enrolled (45 TC, 32 MI, and 30 HC).
Specific stressful events (death of a relative or close friend (p = 0.006);
illness or injury to a relative or close friend (p = 0.001) were more prevalent
in TC cases than MI and HC controls. The onset of TC was associated with exposure
to multiple stressful life events during the 6 months preceding the index
hospitalization (p < 0.001) but not with exposure to an acute, recent event (p =
0.96). CONCLUSIONS: TC onset was associated with specific life events (death or
illness to close relative or friend) and with the number of stressful life events
occurring in the 6 months preceding hospitalization. These findings suggest that
grief and cumulative stress could play a major role in the onset of TC.
PMID- 28417438
TI - Examining the Support Peer Supporters Provide Using Structural Equation Modeling:
Nondirective and Directive Support in Diabetes Management.
AB - BACKGROUND: Little research has examined the characteristics of peer support.
Pertinent to such examination may be characteristics such as the distinction
between nondirective support (accepting recipients' feelings and cooperative with
their plans) and directive (prescribing "correct" choices and feelings). PURPOSE:
In a peer support program for individuals with diabetes, this study examined (a)
whether the distinction between nondirective and directive support was reflected
in participants' ratings of support provided by peer supporters and (b) how
nondirective and directive support were related to depressive symptoms, diabetes
distress, and Hemoglobin A1c (HbA1c). METHODS: Three hundred fourteen
participants with type 2 diabetes provided data on depressive symptoms, diabetes
distress, and HbA1c before and after a diabetes management intervention delivered
by peer supporters. At post-intervention, participants reported how the support
provided by peer supporters was nondirective or directive. Confirmatory factor
analysis (CFA), correlation analyses, and structural equation modeling examined
the relationships among reports of nondirective and directive support, depressive
symptoms, diabetes distress, and measured HbA1c. RESULTS: CFA confirmed the
factor structure distinguishing between nondirective and directive support in
participants' reports of support delivered by peer supporters. Controlling for
demographic factors, baseline clinical values, and site, structural equation
models indicated that at post-intervention, participants' reports of nondirective
support were significantly associated with lower, while reports of directive
support were significantly associated with greater depressive symptoms,
altogether (with control variables) accounting for 51% of the variance in
depressive symptoms. CONCLUSIONS: Peer supporters' nondirective support was
associated with lower, but directive support was associated with greater
depressive symptoms.
PMID- 28417439
TI - Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin
Receptor-Neprilysin Inhibitor.
AB - Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure
with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion
of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with
maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan
(angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h,
respectively. With a two-fold increase in dose, an increase in the area under the
plasma concentration-time curve was proportional for sacubitril, ~1.9-fold for
sacubitrilat, and ~1.7-fold for valsartan in healthy subjects. Following multiple
twice-daily administration, steady-state maximum plasma concentration was reached
within 3 days, showing no accumulation for sacubitril and valsartan, while ~1.6
fold accumulation for sacubitrilat. Sacubitril is eliminated predominantly as
sacubitrilat through the kidney; valsartan is eliminated mainly by biliary route.
Drug-drug interactions of sacubitril/valsartan were evaluated with medications
commonly used in patients with heart failure including furosemide, warfarin,
digoxin, carvedilol, levonorgestrel/ethinyl estradiol combination, amlodipine,
omeprazole, hydrochlorothiazide, intravenous nitrates, metformin, statins, and
sildenafil. Co-administration with sacubitril/valsartan increased the maximum
plasma concentration (~2.0-fold) and area under the plasma concentration-time
curve (1.3-fold) of atorvastatin; however, it did not affect the pharmacokinetics
of simvastatin. Age, sex, or ethnicity did not affect the pharmacokinetics of
sacubitril/valsartan. In patients with heart failure vs. healthy subjects, area
under the plasma concentration-time curves of sacubitril, sacubitrilat, and
valsartan were higher by approximately 1.6-, 2.1-, and 2.3-fold, respectively.
Renal impairment had no significant impact on sacubitril and valsartan area under
the plasma concentration-time curves, while the area under the plasma
concentration-time curve of sacubitrilat correlated with degree of renal function
(1.3-, 2.3-, 2.9-, and 3.3-fold with mild, moderate, and severe renal impairment,
and end-stage renal disease, respectively). Moderate hepatic impairment increased
the area under the plasma concentration-time curves of valsartan and sacubitrilat
~2.1-fold.
PMID- 28417441
TI - Relationships Between Essential Manganese Biology and Manganese Toxicity in
Neurological Disease.
AB - PURPOSE OF REVIEW: Manganese (Mn) is critical for neurodevelopment but also has
been implicated in the pathophysiology of several neurological diseases. We
discuss how Mn requirements intersect with Mn biology and toxicity, and how these
requirements may be altered in neurological disease. Furthermore, we discuss the
emerging evidence that the level of Mn associated with optimal overall efficiency
for Mn biology does not necessarily coincide with optimal cognitive outcomes.
RECENT FINDINGS: Studies have linked Mn exposures with urea cycle metabolism and
autophagy, with evidence that exposures typically neurotoxic may be able to
correct deficiencies in these processes at least short term. The line between Mn
dependent biology and toxicity is thus blurred. Further, new work suggests that
Mn exposures correlating to optimal cognitive scores in children are associated
with cognitive decline in adults. This review explores relationships between Mn
dependent neurobiology and Mn-dependent neurotoxicity. We propose the hypothesis
that Mn levels/exposures that are toxic to some biological processes are
beneficial for other biological processes and influenced by developmental stage
and disease state.
PMID- 28417440
TI - Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism.
AB - PURPOSE OF REVIEW: Epidemiological and animal studies suggest that air pollution
may negatively affect the central nervous system (CNS) and contribute to CNS
diseases. Traffic-related air pollution is a major contributor to global air
pollution, and diesel exhaust (DE) is its most important component. RECENT
FINDINGS: Several studies suggest that young individuals may be particularly
susceptible to air pollution-induced neurotoxicity and that perinatal exposure
may cause or contribute to developmental disabilities and behavioral
abnormalities. In particular, a number of recent studies have found associations
between exposures to traffic-related air pollution and autism spectrum disorders
(ASD), which are characterized by impairment in socialization and in
communication and by the presence of repetitive and unusual behaviors. The
cause(s) of ASD are unknown, and while it may have a hereditary component,
environmental factors are increasingly suspected as playing a pivotal role in its
etiology, particularly in genetically susceptible individuals. Autistic children
present higher levels of neuroinflammation and systemic inflammation, which are
also hallmarks of exposure to traffic-related air pollution. Gene-environment
interactions may play a relevant role in determining individual susceptibility to
air pollution developmental neurotoxicity. Given the worldwide presence of
elevated air pollution, studies on its effects and mechanisms on the developing
brain, genetic susceptibility, role in neurodevelopmental disorders, and possible
therapeutic interventions are certainly warranted.
PMID- 28417443
TI - Time Trends of High Blood Pressure Prevalence, Awareness and Control in the
Italian General Population : Surveys of the National Institute of Health.
AB - INTRODUCTION: High blood pressure (BP) is a major risk factor for cardiovascular
disease. The urgency of the problem was underlined by the World Health
Organization (WHO) Global Action Plan for the prevention and control of
noncommunicable diseases, which recommends a 25% relative reduction in the
prevalence of raised BP by 2020. A surveillance system represents a useful tool
to monitor BP in the general population. Since 1980s, the National Institute of
Health has conducted several surveys of the adult general population, measuring
cardiovascular risk factors by standardized procedures and methods. AIM: To
describe mean BP levels and high BP prevalence from 1978 to 2012 by sex and
quinquennia of age. METHODS: Data were derived from the following three studies:
(i) Risk Factors and Life Expectancy (RIFLE), conducted between 1978 and 2002 in
13 Italian regions (>70,000 persons); (ii) Osservatorio Epidemiologico
Cardiovascolare (OEC), conducted between 1998-2002 in the general population from
all Italian regions (>9000 persons); and (iii) Osservatorio Epidemiologico
Cardiovascolare/Health Examination Survey (OEC/HES), conducted between 2008-2012
in the general population from all Italian regions (>9000 persons). RESULTS: A
significant decrease in mean systolic and diastolic BP levels and prevalence of
high BP from 1978 to 2012 was observed both in men and women. BP and high BP
increased by age classes in all considered periods. BP awareness and control also
improved. CONCLUSION: Our data suggest that BP control could be achieved by 2020,
as recommended by WHO.
PMID- 28417442
TI - Mechanisms of Gene-Environment Interactions in Parkinson's Disease.
AB - PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms
associated with environmental and genetic factors that contribute to the
development of Parkinson's disease (PD). RECENT FINDINGS: Novel genetic
contributors to PD are being identified at a rapid pace in addition to novel
environmental factors. The discovery of mutations in alpha-synuclein and leucine
rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in
vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk
factors have dramatically improved our understanding of mechanisms involved in
the development of PD. However, at the same time, these discoveries have also
added layers of complexity to the disease. Within the last several years, the
genetics associated with PD has dominated the field in many ways; however, the
majority of PD cases are likely due to different combinations of environmental
exposures and genetic susceptibility. The most common toxicants used to model PD
including rotenone, paraquat, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
have been shown to interact with many of the genes linked with PD such as alpha
synuclein. Therefore, an understanding of mechanisms common between genetic and
environmental factors is essential for early detection and successful translation
of potential therapies, which is the ultimate goal.
PMID- 28417444
TI - A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage
in an experimental animal model of cartilage repair.
AB - BACKGROUND: This study compares a traditional parapatellar retinaculum
sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle
joint as a cartilage repair model. FINDINGS: Surgical exposure of the femoral
trochlea of ten Yucatan pigs stifle joint was performed using either a
traditional medial parapatellar approach with retinaculum incision and luxation
of the patella (n = 5) or a minimally invasive (MIS) approach which spared the
patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate
access to the trochlea, enabling the creation of cartilage defects without
difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects
were created in each trochlea. There were no intraoperative complications
observed in either surgical approach. All pigs were allowed full weight-bearing
and full range of motion immediately postoperatively and were euthanized between
2 and 3 weeks. The traditional approach was associated with increased cartilage
wear compared to the MIS approach. Two blinded raters performed gross evaluation
of the trochlea cartilage surrounding the defects according to the modified ICRS
cartilage injury classification. The traditional approach cartilage received a
significantly worse score than the MIS approach group from both scorers (3.2 vs
0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). CONCLUSION: The MIS approach
results in less damage to the trochlear cartilage and faster return to load
bearing activities. As an arthrotomy approach in the porcine model, MIS is
superior to the traditional approach.
PMID- 28417446
TI - Missing atrioventricular echogenic mass during paediatric HeartWare(r)
implantation.
PMID- 28417445
TI - Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic
mouse model of HER-2-positive breast cancer.
AB - Curcumin has shown promising inhibitory activity against HER-2-positive tumor
cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has
previously developed a polymeric microparticle formulation for sustained delivery
of curcumin for chemoprevention. The goal of this study was to examine the
anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic
mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and
mice were examined for tumor appearance and growth. Initiating curcumin
microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3
weeks compared to that in control mice that received empty microparticles. At 12
weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma)
mammary tissue area was significantly decreased in curcumin microparticle-treated
mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels
significantly, which likely contributed to slower tumor formation. When compared
to saline controls, however, blank microparticles accelerated tumorigenesis and
curcumin treatment abrogated this effect, suggesting that PLGA microparticles
enhance tumorigenesis in this model. PLGA microparticle administration was shown
to be associated with higher plasma lactic acid levels and increased activation
of NF-kappaBeta. The unexpected side effects of PLGA microparticles may be
related to the high dose of the microparticles that was needed to achieve
sustained curcumin levels in vivo. Approaches that can decrease the overall dose
of curcumin (for example, by increasing its potency or reducing its clearance
rate) may allow the development of sustained release curcumin dosage forms as a
practical approach to cancer chemoprevention.
PMID- 28417447
TI - Air leak without subcutaneous emphysema in an adult patient due to thyroidectomy.
PMID- 28417448
TI - DECISION-CTO: A "negative" clinical trial? Really?
PMID- 28417449
TI - Citicoline: pharmacological and clinical review, 2016 update.
AB - This review is based on the previous one published in 2010 -Secades JJ.
Citicoline: pharmacological and clinical review, 2010 update. Rev Neurol 2011; 52
(Suppl 2): S1-62-, incorporating 183 new references, having all the information
available to facilitate the access to the information in one document. This
review is focused on the main indications of the drug, as acute stroke and its
sequelae, including the cognitive impairment, and traumatic brain injury and its
sequelae. There are retrieved the most important experimental and clinical data
in both indications.
PMID- 28417450
TI - Exploring the biological activity of condensed tannins and nutritional value of
tree and shrub leaves from native species of the Argentinean Dry Chaco.
AB - BACKGROUND: Tropical tree or shrub leaves are an important source of nutrients
for ruminants and a potential source of biologically active compounds that may
affect ruminal metabolism of nutrients. Therefore, eight woody species from the
native flora of Argentinean Dry Chaco, rich in secondary compounds such as
condensed tannins (CT), were assessed for their nutritional value, CT fractions
and in vitro true digestibility of dry matter, as well as biological activity
(BA). RESULTS: Differences among species were found in contents of total phenol,
protein-precipitating phenols (PPP), bound proteins to PPP (BP) and BP/PPP (P <
0.0001). The BP/PPP ratio reveals differences among species in potential BA as
indicated by protein precipitation. The major CT of each species were isolated
and purified for use as a standard. Although Schinopsis balansae had the most (P
<= 0.05) total CT (19.59% DM), Caesalpinia paraguariensis had greater (P <= 0.05)
BA with the most PPP (530.21% dry matter). Larrea divaricata, at 0.97, followed
by Acacia aroma, at 0.89, had CT with the highest (P <= 0.05) BP/PPP ratios,
followed by Prosopis alba (0.59). CONCLUSION: There were differences in nutritive
value and bioactivity among species. Those with the greatest CT were not
necessarily those with the most BA. Caesalpinia paraguariensis, S. balansae and
L. divaricata were the most promising species as native forage CT sources.
Cercidiurm praecox (20.87% CP; 18.14% acid detergent fiber) and Prosopis nigra
(19.00% CP; 27.96% acid detergent fiber) showed the best (P <= 0.05) nutritive
values. According to their nutritive traits, these species might be complementary
in grass-based ruminant diets. (c) 2017 Society of Chemical Industry.
PMID- 28417451
TI - Prophylactic anti-staphylococcal antibiotics for cystic fibrosis.
AB - BACKGROUND: Staphylococcus aureus causes pulmonary infection in young children
with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent
such infection and lung damage. Antibiotics have adverse effects and long-term
use might lead to infection with Pseudomonas aeruginosa. This is an update of a
previously published review. OBJECTIVES: To assess continuous oral antibiotic
prophylaxis to prevent the acquisition of Staphylococcus aureus versus no
prophylaxis in people with cystic fibrosis, we tested these hypotheses.
Prophylaxis:1. improves clinical status, lung function and survival;2. causes
adverse effects (e.g. diarrhoea, skin rash, candidiasis);3. leads to fewer
isolates of common pathogens from respiratory secretions;4. leads to the
emergence of antibiotic resistance and colonisation of the respiratory tract with
Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis
and Genetic Disorders Group Trials Register, comprising references identified
from comprehensive electronic database searches, handsearches of relevant
journals and abstract books of conference proceedings. Companies manufacturing
anti-staphylococcal antibiotics were contacted.Most recent search of the Group's
Register: 29 September 2016. SELECTION CRITERIA: Randomised trials of continuous
oral prophylactic antibiotics (given for at least one year) compared to
intermittent antibiotics given 'as required', in people with cystic fibrosis of
any disease severity. DATA COLLECTION AND ANALYSIS: The authors assessed studies
for eligibility and methodological quality and extracted data. MAIN RESULTS: We
included four studies, with a total of 401 randomised participants aged zero to
seven years on enrolment; one study is ongoing. The two older included studies
generally had a higher risk of bias across all domains, but in particular due to
a lack of blinding and incomplete outcome data, than the two more recent studies.
We only regarded the most recent study as being generally free of bias, although
even here we were not certain of the effect of the per protocol analysis on the
study results. Evidence was downgraded based on GRADE assessments and outcome
results ranged from moderate to low quality. Downgrading decisions were due to
limitations in study design (all outcomes); for imprecision (number of people
needing additional antibiotics); and for inconsistency (weight z score).Fewer
children receiving anti-staphylococcal antibiotic prophylaxis had one or more
isolates of Staphylococcus aureus (low quality evidence). There was no
significant difference between groups in infant or conventional lung function
(moderate quality evidence). We found no significant effect on nutrition (low
quality evidence), hospital admissions, additional courses of antibiotics (low
quality evidence) or adverse effects (moderate quality evidence). There was no
significant difference in the number of isolates of Pseudomonas aeruginosa
between groups (low quality evidence), though there was a trend towards a lower
cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at
two and three years and towards a higher rate from four to six years. As the
studies reviewed lasted six years or less, conclusions cannot be drawn about the
long-term effects of prophylaxis. AUTHORS' CONCLUSIONS: Anti-staphylococcal
antibiotic prophylaxis leads to fewer children having isolates of Staphylococcus
aureus, when commenced early in infancy and continued up to six years of age. The
clinical importance of this finding is uncertain. Further research may establish
whether the trend towards more children with CF with Pseudomonas aeruginosa,
after four to six years of prophylaxis, is a chance finding and whether choice of
antibiotic or duration of treatment might influence this.
PMID- 28417452
TI - Worldwide pattern of antibiotic prescription in endodontic infections.
AB - BACKGROUND: Odontogenic infections, and especially endodontic infections, are
polymicrobial, involving a combination of Gram-positive and Gram-negative
facultative anaerobes and strictly anaerobic bacteria. Therefore, antibiotics can
be used as an adjunct to endodontic treatment. However, most chronic and even
acute endodontic infections can be successfully managed by disinfection of the
root-canal system, which eliminates the source of infection, followed by abscess
drainage or tooth extraction, without the need for antibiotics. The literature
provides evidence of inadequate prescribing practices by dentists. The aim of
this concise review was to analyse the worldwide pattern of antibiotic
prescription in endodontic infections. METHODS: Comprehensive searches were
conducted in MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus.
The databases were searched up to 13 March 2016 for studies in which dentists
used systemic antibiotics to treat endodontic lesions and which reported data on
the type of antibiotic prescribed and on the diagnosis of the endodontic disease
treated. RESULTS: The electronic and hand searches identified 69 titles, of which
25 were included in the final analysis. Amoxicillin was reported as the drug of
choice for endodontic infections in most countries, and clindamycin and
erythromycin were the choice for patients allergic to penicillin. Dentists
worldwide prescribe antibiotics for non-indicated conditions, such as pulpitis.
CONCLUSION: Antibiotics are overprescribed for the management of endodontic
infections. It is necessary to improve antibiotic-prescribing habits in the
treatment of endodontic infections, as well as to introduce educational
initiatives to encourage the coherent and proper use of antibiotics in such
conditions.
PMID- 28417453
TI - Bilateral cataract surgery with intraocular lens implant in a captive western
lowland gorilla.
AB - We report a case of bilateral cataract surgery performed in a 21-year-old western
lowland gorilla. Phacoemulsification with intraocular lens insertion was
performed using standard human surgical equipment. Visual function significantly
improved. She subsequently mated and gave birth. Ultimately, cataract surgery
enabled the birth of a baby gorilla.
PMID- 28417454
TI - Prevalence and predictors of anxiety in an African sample of recent stroke
survivors.
AB - OBJECTIVES: Studies considering emotional disturbances in the setting of stroke
have primarily focused on depression and been conducted in high-income countries.
Anxiety in stroke survivors, which may be associated with its own unique sets of
risk factors and clinical parameters, has been rarely investigated in sub-Saharan
Africa (SSA). We assess the characteristics of anxiety and anxiety-depression
comorbidity in a SSA sample of recent stroke survivors. MATERIALS AND METHODS: We
assessed baseline data being collected as part of an intervention to improve one
year blood pressure control among recent (<=1 month) stroke survivors in SSA.
Anxiety in this patient population was measured using the Hospital Anxiety and
Depression Scale (HADS), while the community screening instrument for dementia
was used to evaluate cognitive functioning. Independent associations were
assessed using logistic regression analysis. RESULTS: Among 391 participants,
clinically significant anxiety (HADS anxiety score>=11) was found in 77 (19.7%).
Anxiety was comorbid with depression in 55 (14.1%). Female stroke survivors were
more likely than males to have anxiety (OR=2.4, 95% CI=1.5-4.0). Anxiety was
significantly associated with the presence of cognitive impairment after
adjusting for age, gender and education (OR=6.8, 95% CI=2.6-18.0). CONCLUSIONS:
One in five recent stroke survivors in SSA has clinically significant anxiety,
and well over 70% of those with anxiety also have depression. Future studies will
need to determine what specific impact post-stroke anxiety may have on post
stroke clinical processes and outcomes.
PMID- 28417455
TI - An efficient process for obtaining prebiotic oligosaccharides derived from
lactulose using isomerized and purified whey permeate.
AB - BACKGROUND: One of the most promising uses of whey permeate (WP) is the synthesis
of prebiotic oligosaccharides. Herein, commercial WP was submitted to chemical
isomerization catalysed by sodium borate at an alkaline pH and subsequent
purification using anion-exchange resins to remove boron. Subsequently, purified
mixtures were used to synthesize prebiotic oligosaccharides using beta
galactosidase from Bacillus circulans. RESULTS: Isomerization of concentrated WP
(200 g L-1 lactose) gave rise to levels of lactulose up to 155.5 g L-1 after 30
min of reaction (molar ratio of boron/lactose, 1/1; pH 12; 70 degrees C). Boron
was removed from the isomerized WP (IWP) using the combination of a strong acid
(IR-120, H+ ) and a weak base (IRA-743) anion-exchange resins, reducing its level
to <1 ppm, without loss of lactulose. During the transglycosylation reaction of
purified IWP (lactose/lactulose ratio, 1/2.4) maximum content of prebiotic
compounds was achieved, i.e. 690 g kg-1 WP after 3 h of reaction. CONCLUSION:
This study shows that combined chemical-enzymatic reactions together with the
purification of IWP results in an efficient synthesis of prebiotic
oligosaccharides. (c) 2017 Society of Chemical Industry.
PMID- 28417456
TI - Interventions to improve adherence to inhaled steroids for asthma.
AB - BACKGROUND: Despite its proven efficacy in improving symptoms and reducing
exacerbations, many patients with asthma are not fully adherent to their steroid
inhaler. Suboptimal adherence leads to poorer clinical outcomes and increased
health service utilisation, and has been identified as a contributing factor to a
third of asthma deaths in the UK. Reasons for non-adherence vary, and a variety
of interventions have been proposed to help people improve treatment adherence.
OBJECTIVES: To assess the efficacy and safety of interventions intended to
improve adherence to inhaled corticosteroids among people with asthma. SEARCH
METHODS: We identified trials from the Cochrane Airways Trials Register, which
contains studies identified through multiple electronic searches and handsearches
of other sources. We also searched trial registries and reference lists of
primary studies. We conducted the most recent searches on 18 November 2016.
SELECTION CRITERIA: We included parallel and cluster randomised controlled trials
of any duration conducted in any setting. We included studies reported as full
text articles, those published as abstracts only and unpublished data. We
included trials of adults and children with asthma and a current prescription for
an inhaled corticosteroid (ICS) (as monotherapy or in combination with a long
acting beta2-agonist (LABA)). Eligible trials compared an intervention primarily
aimed at improving adherence to ICS versus usual care or an alternative
intervention. DATA COLLECTION AND ANALYSIS: Two review authors screened the
searches, extracted study characteristics and outcome data from included studies
and assessed risk of bias. Primary outcomes were adherence to ICS, exacerbations
requiring at least oral corticosteroids and asthma control. We graded results and
presented evidence in 'Summary of findings' tables for each comparison.We
analysed dichotomous data as odds ratios, and continuous data as mean differences
or standardised mean differences, all using a random-effects model. We described
skewed data narratively. We made no a priori assumptions about how trials would
be categorised but conducted meta-analyses only if treatments, participants and
the underlying clinical question were similar enough for pooling to make sense.
MAIN RESULTS: We included 39 parallel randomised controlled trials (RCTs)
involving adults and children with asthma, 28 of which (n = 16,303) contributed
data to at least one meta-analysis. Follow-up ranged from two months to two years
(median six months), and trials were conducted mainly in high-income countries.
Most studies reported some measure of adherence to ICS and a variety of other
outcomes such as quality of life and asthma control. Studies generally were at
low or unclear risk of selection bias and at high risk of biases associated with
blinding. We considered around half the studies to be at high risk for attrition
bias and selective outcome reporting.We classified studies into four comparisons:
adherence education versus control (20 studies); electronic trackers or reminders
versus control (11 studies); simplified drug regimens versus usual drug regimens
(four studies); and school-based directly observed therapy (three studies). Two
studies are described separately.All pooled results for adherence education,
electronic trackers or reminders and simplified regimens showed better adherence
than controls. Analyses limited to studies using objective measures revealed that
adherence education showed a benefit of 20 percentage points over control (95%
confidence interval (CI) 7.52 to 32.74; five studies; low-quality evidence);
electronic trackers or reminders led to better adherence of 19 percentage points
(95% CI 14.47 to 25.26; six studies; moderate-quality evidence); and simplified
regimens led to better adherence of 4 percentage points (95% CI 1.88 to 6.16;
three studies; moderate-quality evidence). Our confidence in the evidence was
reduced by risk of bias and inconsistency.Improvements in adherence were not
consistently translated into observable benefit for clinical outcomes in our
pooled analyses. None of the intervention types showed clear benefit for our
primary clinical outcomes - exacerbations requiring an oral corticosteroid (OCS)
(evidence of very low to low quality) and asthma control (evidence of low to
moderate quality); nor for our secondary outcomes - unscheduled visits (evidence
of very low to moderate quality) and quality of life (evidence of low to moderate
quality). However, some individual studies reported observed benefits for OCS and
use of healthcare services. Most school or work absence data were skewed and were
difficult to interpret (evidence of low quality, when graded), and most studies
did not specifically measure or report adverse events.Studies investigating the
possible benefit of administering ICS at school did not measure adherence,
exacerbations requiring OCS, asthma control or adverse events. One study showed
fewer unscheduled visits, and another found no differences; data could not be
combined. AUTHORS' CONCLUSIONS: Pooled results suggest that a variety of
interventions can improve adherence. The clinical relevance of this improvement,
highlighted by uncertain and inconsistent impact on clinical outcomes such as
quality of life and asthma control, is less clear. We have low to moderate
confidence in these findings owing to concerns about risk of bias and
inconsistency. Future studies would benefit from predefining an evidence-based
'cut-off' for acceptable adherence and using objective adherence measures and
validated tools and questionnaires. When possible, covert monitoring and some
form of blinding or active control may help disentangle effects of the
intervention from effects of inclusion in an adherence trial.
PMID- 28417457
TI - Effects of riboflavin and ultraviolet light treatment on platelet thrombus
formation and thrombus stability on collagen.
AB - BACKGROUND: Pathogen reduction technologies (PRTs) are considered for the
implementation of safer platelet (PLT) transfusion. PRT treatment involves the
addition of a photosensitizer to a blood component followed by ultraviolet (UV)
light irradiation. However, the effects of PRT treatment on PLT thrombus
formation and thrombus stability have not been satisfactorily clarified. STUDY
DESIGN AND METHODS: Leukoreduced PLT concentrates (PCs) were treated with
riboflavin and UV light (Mirasol PRT). PLT thrombus formation on collagen was
evaluated by the microchannel method, by which the total amount of PLTs deposited
was measured as indices of thrombus formation and thrombus stability. Using a
cone-plate shear-induced PLT aggregometer, PLT reactivity in blood flow was
examined in a wide range of shear stresses of 6 to 108 dyn/cm2 . RESULTS: There
was no significant difference in surface coverage between PRT-treated PLTs and
control PLTs on collagen. On the other hand, the total amount of PRT-treated PLTs
deposited was higher than that of control PLTs. The promotive effect of PRT
treatment on PLT deposition completely disappeared in the presence of tirofiban,
a potent integrin alphaIIbbeta3 inhibitor. The percentage of the dissociation of
PRT-treated PLTs on collagen was lower than that of control PLTs after flushing
with phosphate-buffered saline. PRT treatment significantly inhibited PLT
aggregation under high-shear-stress conditions. CONCLUSION: Riboflavin-based PRT
treatment of PCs leads to the enhancement of PLT thrombus formation and thrombus
stability on collagen. However, it does not enhance the reactivity of PLTs not in
contact with collagen under high-shear-stress conditions.
PMID- 28417458
TI - Resistin causes G1 arrest in colon cancer cells through upregulation of SOCS3.
AB - Resistin, a proinflammatory cytokine, is elevated in a number of pathological
disorders, including cancer. The serum resistin level in colon cancer patients is
elevated and correlates with tumor grade. However, the implications of increased
resistin on colon cancer cells remain unclear. In the present study, we find that
resistin binds to TLR4 on colon cancer cell membrane and initiates TLR4-MyD88
dependent activation of ERK. In addition, the upregulation of SOCS3 by ERK
downregulates the JAK2/TAT3 pathway and causes the arrest of cells in G1 phase.
Interestingly, we observe that resistin-exposed cells survive 5-fluorouracil
treatment because of a decrease in drug uptake due to the arrest of cells in G1
phase.
PMID- 28417459
TI - Does obesity complicate regional anesthesia and result in longer decision to
delivery time for emergency cesarean section?
AB - BACKGROUND: Maternal obesity can cause problems with anesthesia and surgery which
may be reflected in emergency cesarean sections (CS) as an increased decision-to
delivery interval (DDI). AIM: To study the association of elevated maternal BMI
with DDI and the failure of regional anesthesia. METHODS: Eight hundred and forty
two consecutive emergency CSs during a period of 1 year in a tertiary hospital
were studied retrospectively. DDIs were analyzed in Crash and < 30-min urgency
categories (n = 528), while the time required to establish regional anesthesia
and its success were analyzed for all emergency CS cases. RESULTS: The urgency
distribution of the CSs was 11%, 52%, and 37% in Crash, < 30-min, and > 30-min
urgency categories respectively. Increased BMI was associated with longer DDI
time in the < 30-min urgency category (33(13-176) vs. 38(18-118) min; P < 0.05
for BMI < 30 and > 35 group respectively). Regional anesthesia failures (new
regional anesthesia, conversion to general anesthesia, or complaint of pain
during surgery) took place in 3.7%, 6.8%, and 8.5% in the BMI < 30, 30-35, and >
35 groups respectively (P = 0.021). Epidural top-up resulted in shorter DDI and
time delay between arrival at the operating room and skin incision across all
urgency and BMI groups than combined spinal epidural (CSE) anesthesia.
CONCLUSION: Higher BMI was associated with longer DDI and more regional
anesthesia failures. Epidural top-up was faster than CSE for establishing CS
anesthesia.
PMID- 28417460
TI - Effect of high-fat diet and growth stage on the diversity and composition of
intestinal microbiota in healthy bovine livestock.
AB - BACKGROUND: This study aimed to investigate the composition of bacteria in the
bovine rectum and their functions during growth, in relation to different diets.
Fecal samples were collected from 6-, 12-, 18- and 24-month cattle fed high-fat
diet, and healthy female parents fed regular diet. Total DNA was amplified (V3-V4
of 16S rRNA) and submitted to barcode-DNA pyrosequencing. Intestinal microbiota
profiles and functions were then analyzed. RESULTS: A total of 114 512
operational taxonomic units were detected from the 1 802 243 sequences obtained.
In 6-month-old and female parent groups, the top three abundant phyla were
Bacteroidetes (37.6%, 32.2%), Firmicutes (34.4%, 48.2%) and Proteobacteria (9.1%,
6.3%); in the 12-, 18- and 24-month groups, they were Proteobacteria (45.5%,
47.1%, 38.8%), Firmicutes (27.4%, 22.2%, 20.1%) and Bacteroidetes (14.9%, 19.4%,
17.7%), respectively. Paludibacter and Desulfopila in abundance showed negative
(P < 0.001) and positive (P < 0.05) correlation, respectively, to cattle weight
gain through metagenomic functional prediction of methane, cysteine and
methionine metabolism. Meanwhile, cofactor/vitamin and amino acid metabolic
processes were significantly higher in bacteria from the regular diet group than
high-fat diet groups, with markedly lower cellular processes and signaling, and
reduced glycan biosynthesis and metabolism (P < 0.01). CONCLUSIONS: The 6-month
cattle and female parents shared similar intestinal bacteria; the community
structure of fecal microbiota was significantly affected by high-fat diet in
older cattle. (c) 2017 Society of Chemical Industry.
PMID- 28417461
TI - The pathway intermediate 2-keto-3-deoxy-L-galactonate mediates the induction of
genes involved in D-galacturonic acid utilization in Aspergillus niger.
AB - In Aspergillus niger, the enzymes encoded by gaaA, gaaB, and gaaC catabolize d
galacturonic acid (GA) consecutively into l-galactonate, 2-keto-3-deoxy-l
galactonate, pyruvate, and l-glyceraldehyde, while GaaD converts l-glyceraldehyde
to glycerol. Deletion of gaaB or gaaC results in severely impaired growth on GA
and accumulation of l-galactonate and 2-keto-3-deoxy-l-galactonate, respectively.
Expression levels of GA-responsive genes are specifically elevated in the ?gaaC
mutant on GA as compared to the reference strain and other GA catabolic pathway
deletion mutants. This indicates that 2-keto-3-deoxy-l-galactonate is the inducer
of genes required for GA utilization.
PMID- 28417462
TI - Exploring patient satisfaction levels, self-rated oral health status and
associated variables among citizens covered for dental insurance through a
National Social Security Scheme in India.
AB - OBJECTIVE: To assess patient satisfaction, self-rated oral health and associated
factors, including periodontal status and dental caries, among patients covered
for dental insurance through a National Social Security Scheme in New Delhi,
India. METHOD: A total of 1,498 patients participated in the study. Satisfaction
levels and self-rated oral-health scores were measured using a questionnaire
comprising 12 closed-ended questions. Clinical data were collected using the
Community Periodontal Index (CPI) and the decayed, missing and filled teeth
(DMFT) index. Regression analysis was conducted to evaluate factors associated
with dental caries, periodontal status and self-rated oral health. RESULTS: Areas
of concern included poor cleanliness within the hospital, extensive delays for
appointments, waiting time in hospital and inadequate interpersonal and
communication skills among health-care professionals. Approximately 51% of the
respondents rated their oral health as fair to poor. Younger age, no tobacco
usage, good periodontal status and absence of dental caries were significantly
associated with higher oral health satisfaction, with odds ratios of 3.94, 2.38,
2.58 and 2.09, respectively (P <= 0.001). CONCLUSION: The study indicates poor
satisfaction levels with the current dental care system and a poor self-rated
oral health status among the study population. Some specific areas of concern
have been identified. These findings may facilitate restructuring of the existing
dental services under the National Social Security Scheme towards creating a
better patient care system.
PMID- 28417463
TI - Pharmacological interventions for primary sclerosing cholangitis: an attempted
network meta-analysis.
AB - BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease
that is associated with both hepatobiliary and colorectal malignancies, which can
result in liver cirrhosis and its complications. The optimal pharmacological
treatment for patients with primary sclerosing cholangitis remains controversial.
OBJECTIVES: To assess the comparative benefits and harms of different
pharmacological interventions in people with primary sclerosing cholangitis by
performing a network meta-analysis, and to generate rankings of available
pharmacological interventions according to their safety and efficacy. Given that
it was not possible to assess whether potential effect modifiers were similar
across comparisons, we did not perform the network meta-analysis but instead used
standard Cochrane methods.When trials begin to provide an adequate description of
potential effect modifiers, we will attempt to conduct network meta-analysis.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index -
Expanded, the WHO International Clinical Trials Registry Platform, and randomised
controlled trials registers until February 2017 to identify randomised clinical
trials (RCT) on pharmacological interventions for primary sclerosing cholangitis.
SELECTION CRITERIA: We included only RCTs, irrespective of language, blinding, or
publication status, in which participants were given a diagnosis of primary
sclerosing cholangitis. We excluded trials that included previously liver
transplanted participants. We considered any of various pharmacological
interventions compared with one other or with placebo. We excluded trials that
compared different doses of various pharmacological interventions or that
reported different treatment durations, except for ursodeoxycholic acid (UDCA).
As UDCA is the drug most commonly investigated for primary sclerosing
cholangitis, we performed a second analysis in which we stratified the dose of
UDCA. DATA COLLECTION AND ANALYSIS: We calculated the odds ratio and the rate
ratio with 95% confidence intervals (CIs) using both fixed-effect and random
effects models based on available-participant analysis with Review Manager. We
assessed risk of bias according to Cochrane, controlled risk of random errors
with Trial Sequential Analysis, and assessed the quality of the evidence using
GRADE. MAIN RESULTS: We identified 22 RCTs in which 1211 participants were
randomised to 13 different interventions. Most were placebo-controlled trials.
Trials had few restrictions apart from an established diagnosis of primary
sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver
disease, and absence of malignancy. However, some trials included symptomatic
participants only, and others included both symptomatic and asymptomatic
participants. A total of 11 RCTs (706 participants) provided data for one or more
outcomes. The period of follow-up ranged from three months to three years in most
trials. Only three trials reported follow-up longer than three years.
Investigators found no evidence of differences in important clinical benefits
such as reduction in mortality at maximal follow-up and improvement in health
related quality of life. Primary outcomes Mortality: Effect estimates: colchicine
versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one
trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58,
participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI
0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo:
odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%;
vancomycin versus placebo: not estimable because no events in either group,
participants = 29, one trial. Serious adverse events (proportion): Effect
estimates: infliximab versus placebo: odds ratio not estimable (because of zero
events in both arms), participants = 7, one trial; steroids versus placebo: odds
ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin
versus placebo: not estimable because no events in either group, participants =
29, one trial. Serious adverse events (number): Effect estimates: infliximab
versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one
trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83,
participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI
0.71 to 15.62, participants = 11, one trial. Adverse events (proportion): Effect
estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90,
participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio
1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus
placebo: not estimable because no events in either group, participants = 29, one
trial. Adverse events (number): Effect estimates: cyclosporin versus placebo:
rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids
versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one
trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate
ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial. Health-related
quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95%
CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General
Health Scale). Secondary outcomes Studies provided no evidence of differences in
clinical benefits such as a reduction in the requirement for liver
transplantation or a reduction in the incidence proportion of cholangiocarcinoma.
One small trial (29 participants) comparing vancomycin versus placebo reported no
malignancies, no liver decompensation, and no liver transplantation in either
group after a very short follow-up period of 12 weeks after treatment. None of
the remaining trials clearly reported other clinical benefits such as decreased
development of all malignancies, colorectal cancer, liver decompensation, time to
liver decompensation, time to liver transplantation, or requirement for
cholecystectomy to allow comparisons between different interventions. SOURCE OF
FUNDING: Fifteen trials reported the source of funding; three were funded by
parties without vested interest in results of the trial, and 12 were funded in
part or in full by drug companies. AUTHORS' CONCLUSIONS: Evidence is currently
insufficient to show differences in effectiveness measures such as mortality,
health-related quality of life, cirrhosis, or liver transplantation between any
active pharmacological intervention and no intervention. However, trials were at
high risk of bias and included small numbers of participants, had short follow-up
periods, and reported few clinical outcomes. An urgent need exists to identify an
effective medical treatment for primary sclerosing cholangitis through well
designed RCTs with adequate follow-up that aim to identify differences in
outcomes important to people with primary sclerosing cholangitis.
PMID- 28417464
TI - Qualitative and quantitative analysis of endophyte alkaloids in perennial
ryegrass using near-infrared spectroscopy.
AB - BACKGROUND: Near-infrared reflectance spectroscopy (NIRS) has been widely used in
forage quality control because it is faster, cleaner and less expensive than
conventional chemical procedures. In Lolium perenne (perennial ryegrass), one of
the most important forage grasses, the infection by asymptomatic Epichloe fungal
endophytes alters the plant nutritional quality due to the production of
alkaloids. In this research, we developed a rapid method based on NIRS to detect
and quantify endophyte alkaloids (peramine, lolitrem B and ergovaline) using a
heterogeneous set of L. perenne plants obtained from wild grasslands and
cultivars. RESULTS: NIR spectra from dried grass samples were recorded and
classified according to the absence or presence of alkaloids, based on reference
methods. The best discriminant equations for detection of alkaloids classified
correctly 94.4%, 87.5% and 92.9% of plants containing peramine, lolitrem B and
ergovaline, respectively. The quantitative NIR equations obtained by modified
partial least squares (MPLS) algorithm had coefficients of correlation of 0.93,
0.41, and 0.76 for peramine, lolitrem B and ergovaline respectively. CONCLUSION:
NIRS is a suitable tool for qualitative analysis of endophyte alkaloids in
grasses and for the accurate quantification of peramine and ergovaline. (c) 2017
Society of Chemical Industry.
PMID- 28417465
TI - Effects of rare sugar d-allulose on heat-induced gelation of surimi prepared from
marine fish.
AB - BACKGROUND: d-Allulose (Alu), the C3-epimer of d-fructose, is a non-caloric
sweetener (0.39 kcal g-1 ) with a suppressive effect on postprandial blood
glucose elevation. The aim of this study was to investigate the effects of Alu
used as a sweetener and gel improver instead of sucrose on heat-induced gelation
of surimi. RESULTS: The puncture test of a heat-induced surimi gel showed that
with 50 g kg-1 Alu the gel had 15% and 6% higher gel strength than the
corresponding gel with sucrose (Suc) and with sorbitol (Sor), respectively. In
addition, Alu-gel had 26% and 25% higher water-holding capacity (WHC) than Suc-
and Sor-gel. Heating of myofibrillar protein with Alu, unlike Suc and Sor,
facilitated the formation of both disulfide and non-disulfide crosslinks that
might be associated with the mechanical properties and WHC of Alu-gel.
CONCLUSION: Alu improves the mechanical properties and WHC of the heat-induced
surimi gel. Furthermore, Alu is low in calories compared with Suc (4.0 kcal g-1 )
and Sor (3.0 kcal g-1 ). Thus Alu will be an alternative of Suc or Sor for
developing surimi-based products with health benefits. (c) 2017 Society of
Chemical Industry.
PMID- 28417466
TI - S-nitrosoglutathione spraying improves stomatal conductance, Rubisco activity and
antioxidant defense in both leaves and roots of sugarcane plants under water
deficit.
AB - Water deficit is a major environmental constraint on crop productivity and
performance and nitric oxide (NO) is an important signaling molecule associated
with many biochemical and physiological processes in plants under stressful
conditions. This study aims to test the hypothesis that leaf spraying of S
nitrosoglutathione (GSNO), an NO donor, improves the antioxidant defense in both
roots and leaves of sugarcane plants under water deficit, with positive
consequences for photosynthesis. In addition, the roles of key photosynthetic
enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and
phosphoenolpyruvate carboxylase (PEPC) in maintaining CO2 assimilation of GSNO
sprayed plants under water deficit were evaluated. Sugarcane plants were sprayed
with water or GSNO 100 MUM and subjected to water deficit, by adding polyethylene
glycol (PEG-8000) to the nutrient solution. Sugarcane plants supplied with GSNO
presented increases in the activity of antioxidant enzymes such as superoxide
dismutase in leaves and catalase in roots, indicating higher antioxidant capacity
under water deficit. Such adjustments induced by GSNO were sufficient to prevent
oxidative damage in both organs and were associated with better leaf water
status. As a consequence, GSNO spraying alleviated the negative impact of water
deficit on stomatal conductance and photosynthetic rates, with plants also
showing increases in Rubisco activity under water deficit.
PMID- 28417467
TI - Retraction Statement: CXCL12/CXCR4 chemokine signaling in spinal glia induces
pain hypersensitivity through MAPKs-mediated neuroinflammation in bone cancer
rats.
AB - 'CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity
through MAPKs-mediated neuroinflammation in bone cancer rats' by Hu X.-M., Liu Y.
N., Zhang H.-L., Cao S.-B., Zhang T., Chen L.-P. and Shen W. The above article
from Journal of Neurochemistry, published online on 26 January 2015 and in volume
132, issue 4, pages 452-463 (available through www.onlinelibrary.wiley.com), and
its subsequent Corrigendum, published online on 5 February 2015 and in volume
132, issue 4, p. 487, have been retracted by agreement between the Journal's
Editor-in-Chief, Jorg Schulz, corresponding author Wen Shen on behalf of the
authors, and John Wiley & Sons Ltd. The retraction has been agreed as the same
GFAP immunostaining image was used to represent different experimental conditions
in two different publications (Shen et al. [2014] in the Journal of
Neuroinflammation and Hu et al. [2015] in the Journal of Neurochemistry), with
apparent brightness changes between the images. Shen et al. (2014) show in the
outer right panel of Figure 4a, as well as in Fig. 8A for the GFAP/sham
condition, a GFAP immunostaining after treatment with TCI + Fluorocitrate. The
same image, at a lower intensity, is used in Hu et al. (2015) in the first panel
of figure 5b as a sham control. The shape of the tissue margins of the spinal
cord section as well as several landmark epitopes that point towards identical
images are encircled: Shen et al. 2014 Figure 4a Hu et al. 2015 Figure 5b Shen et
al. 2014 Figure 8a The authors confirmed that 'The research published in JNC
sequentially builds on our previous study published in Journal of
Neuroinflammation, as we have mentioned in the discussion. So, at the beginning,
we performed these experiments and wrote these two manuscripts together,' whereas
the statements in the Hu et al. paper, 'The testing procedure was performed
according to previously standardized protocols (Hargreaves et al. 1988) and our
published report (Shen et al. 2014) ... confirmed our previous report (Shen et
al. 2014)' imply that the Hu et al. study was a follow-up based on a new original
data set. The authors were given the opportunity to respond and to provide the
original raw images. Several Sham group GFAP immunostainings were sent. However,
the reliability of the data that was presented in the publication could not be
confirmed and the paper is therefore being retracted. A corrigendum related to a
different problem with data representation that was previously issued for this
paper is also being retracted (Hu et al. 2015, Corrigendum). References Hu X. M.,
Liu Y. N., Zhang H. L., Cao S. B., Zhang T., Chen L. P. and Shen W. (2015a)
CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity
through MAPKS-mediated neuroinflammation in bonce cancer rats. J. Neurochem. 132,
452-463. doi:10.1111/jnc.12985. Hu X. M., Liu Y. N., Zhang H. L., Cao S. B.,
Zhang T., Chen L. P. and Shen W. (2015b) Corrigendum. J. Neurochem. 132, 487.
doi:10.1111/jnc.13054. Shen W., Hu X. M., Liu Y. N., Han Y., Chen L. P., Wang C.
C. and Song C. (2014) CXCL12 in astrocytes contributes to bone cancer pain
through CXCR4-mediated neuronal sensitization and glial activation in rat spinal
cord. J. Neuroinflammation 11, 75. doi:10.1186/1742-2094-11-75.
PMID- 28417468
TI - Corrigendum.
PMID- 28417469
TI - Oesophageal involvement in 26 consecutive patients with mucous membrane
pemphigoid.
AB - BACKGROUND: Oesophageal involvement of mucous membrane pemphigoid (MMP) has not
yet been thoroughly described. OBJECTIVES: To characterize systematically the
endoscopic lesions of a series of patients with oesophageal symptoms seen at a
referral centre for autoimmune bullous diseases. METHODS: Clinical, endoscopic
and immunological findings of consecutively referred patients with MMP with
oesophageal involvement, systemic and endoscopic treatments, and follow-up are
described. RESULTS: Of 477 consecutive patients with MMP consulting between 2002
and 2012, 26 (5.4%) had symptomatic oesophageal involvement. Dysphagia, observed
in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could
be the first sign of MMP. Patients with oesophageal involvement had a mean of
three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients
had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s)
and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal
symptom relief for five patients. Dilatation was combined with systemic therapy
for 12 patients and was successful in nine; one perforation occurred.
CONCLUSIONS: Symptomatic oesophageal involvement affected 5.4% of patients with
MMP. Dermatologists and gastroenterologists should be aware of these
mucocutaneous diseases and their oesophageal involvement, as it could lead to
earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic
option for symptomatic stricture not relieved by optimized systemic therapy
alone.
PMID- 28417470
TI - Stress, death, and the biological glue of sinking matter.
PMID- 28417471
TI - Assessing the impact of selection bias on test decisions in trials with a time-to
event outcome.
AB - If past treatment assignments are unmasked, selection bias may arise even in
randomized controlled trials. The impact of such bias can be measured by
considering the type I error probability. In case of a normally distributed
outcome, there already exists a model accounting for selection bias that permits
calculating the corresponding type I error probabilities. To model selection bias
for trials with a time-to-event outcome, we introduce a new biasing policy for
exponentially distributed data. Using this biasing policy, we derive an exact
formula to compute type I error probabilities whenever an F-test is performed and
no observations are censored. Two exemplary settings, with and without random
censoring, are considered in order to illustrate how our results can be applied
to compare distinct randomization procedures with respect to their performance in
the presence of selection bias. (c) 2017 The Authors. Statistics in Medicine
Published by John Wiley & Sons Ltd.
PMID- 28417472
TI - Evaluation of Liver, Kidney, and Spleen Elasticity in Healthy Newborns and
Infants Using Shear Wave Elastography.
AB - OBJECTIVES: Elasticity measurements of tissues can be valuable in the diagnosis
and management of various diseases. The aim of this study was to determine the
elasticity values for normal liver, kidney, and spleen of healthy newborns and
infants using shear wave elastography (SWE) imaging. METHODS: A total of 50
healthy term newborns and infants (19 girls and 31 boys; mean age 20.1 days,
range 1 to 70 days) were examined by an experienced pediatric radiologist using
SWE. None of them had any liver, kidney or spleen disease, or any other systemic
disease that could affect these organs secondarily. All newborns and infants had
a normal abdominal ultrasound scan. RESULTS: Age, sex, weight, height, and body
mass index had no significant effects on shear wave velocity (SWV) values of
liver and spleen. The SWV values of both kidneys decreased with age, weight,
height, and body mass index. The mean SWV values were 1.70 m/s (range: 1.23-2.43
m/s) for the liver, 1.69 m/s (range: 0.8-2.40 m/s) for the right kidney, 1.70 m/s
(range: 0.9-2.49 m/s) for the left kidney, and 2.03 m/s (range: 1.28-2.48 m/s)
for the spleen. CONCLUSIONS: Shear wave elastography can be used to measure
liver, kidney, and spleen elasticity in newborns and infants. The standard values
for abdominal organs allow differentiation of healthy versus pathological tissue.
We measured the normal values of SWE in healthy newborns and infants as reference
data.
PMID- 28417473
TI - Ophthalmology patients' interest in online access to clinic notes at three US
clinics.
AB - PURPOSE: This study aimed to understand patients' perceptions about potential
benefits and harms of accessing their own ophthalmology clinic notes via an
electronic patient portal as part of the OpenNotes initiative. METHODS: The
authors conducted a cross-sectional, in-person survey of ophthalmology patients
at three US eye clinics. The paper survey was self-administered or administered
with assistance from study staff before or after patients' clinical visits. The
authors used descriptive statistics to summarise patient characteristics and
patient attitudes about accessing their ophthalmology notes online. Chi-square
and t-tests were performed to assess differences in patient responses between
clinic locations. RESULTS: Four hundred and fifty-one patients responded
(response rate 65%). Most patients thought that accessing doctors' notes online
was a good idea (95%), wanted to view their clinic notes online (94%), and agreed
online access would increase their understanding of their eye problems (95%) and
help them better remember their care plan (94%); 14% said online access would
increase their worry; 43% had privacy concerns; and 96% indicated they would show
or discuss their notes with at least one other person. Non-white patients were
more likely than white patients to perceive online clinic notes as a useful tool,
but they were also more likely to worry and to express greater privacy concerns.
CONCLUSIONS: Patients at three US eye clinics were strongly in favour of online
access to ophthalmology notes and were optimistic this access would improve their
understanding and self-care. Ophthalmologists should consider offering online
access to their notes to enhance doctor-patient communication and improve
clinical outcomes.
PMID- 28417474
TI - First-Trimester Sonographic Evaluation of Palatine Clefts: A Novel Diagnostic
Approach.
AB - OBJECTIVES: Sonographic evaluation of the palate is a difficult task, and most
palatine clefts are diagnosed in the neonatal period because of the limitations
of 2-dimensional (2D) sonography. The objective is to describe a sonographic
technique based on 2D markers for screening of palatine clefts during the nuchal
translucency scan and to assess the ability of 3-dimensional (3D) sonography in
imaging the normal and abnormal palate. METHODS: A total of 2014 women who
enrolled for first-trimester screening were included in this prospective study.
Screening for palatine clefts was done by 2D evaluation of bony landmarks of the
palate, which were the appearance of the palatal line in the sagittal view,
retronasal triangle in the coronal view, and alveolar ridge of the maxilla in the
axial view followed, by 3D evaluation in suspicious cases. All cases included in
the study were followed by second-trimester anomaly scans and evaluated
postnatally. Additionally, in 100 consecutive normal cases, 3D evaluation of the
palate was done. RESULTS: Visualization of 2D landmarks could be done in all, and
3D assessment was feasible in 94% of cases. Fourteen cases, of which 5 were
unilateral, 4 bilateral, and 2 median cleft lip and palate, 2 median cleft
palate, and 1 atypical palatine cleft were identified. There were no false
positives results reported, and 1 case of a bifid uvula was missed. CONCLUSIONS:
The study demonstrates that evaluation of the palate can be done at the 11 to 14
week scan based on 2D markers and can also be assessed with 3D sonography. The
inclusion of 2D markers in all 3 planes increases the sensitivity for detection
of palatine clefts.
PMID- 28417475
TI - The Role of Early Gestation Ultrasound in the Assessment of Fetal Anatomy in
Maternal Obesity.
AB - OBJECTIVES: The 2012 Eunice Kennedy Shriver National Institute of Child Health
fetal imaging consensus suggested that fetal anatomy ultrasound in obese
pregnancies be performed at 20 to 22 weeks, with follow-up in 2 to 4 weeks if
anatomy is incomplete. It was postulated that imaging in early gestation may
improve visualization, although no prospective trials had been done to date.
METHODS: We performed a prospective longitudinal blinded trial comparing an early
gestation ultrasound (13 + 0 to 15 + 6 weeks) with the traditional second
trimester ultrasound for completion of the fetal anatomy survey in obese
patients. Inclusion criteria included singleton gestation, body mass index (BMI)
more than 30, less than 16 + 0 weeks' gestation, and no karyotype abnormality;
exclusion criteria included age younger than 18 years, more than 16 weeks'
gestation at time of consent, and BMI less than 30. Participants received a
transvaginal and/or transabdominal sonogram for fetal anatomic survey at 13 + 0
to 15 + 6 weeks' gestation (US1). Images from US1 were blinded to physicians and
sonographers performing subsequent examinations. All participants underwent the
traditional transabdominal sonogram at 18 to 24 weeks (US2). If US2 failed to
complete the anatomic survey, a repeat transabdominal sonogram (2-US2) was
performed 2 to 4 weeks later. RESULTS: A total of 152 pregnancies met the
criteria. Anatomy completion rate was 57.2% for US1 and 62.5% for US2, which was
not statistically significant, even when stratified by BMI. Excluding the
philtrum, the US1 performed better than US2 for class III obesity (65.5% versus
45.5% [P = .035]). Combination of US1 + US2 yielded a higher completion rate than
US2 + 2-US2 (94.1% versus 83.6% [P = .0023]). CONCLUSIONS: In the setting of
maternal obesity, the addition of an ultrasound in early gestation may be of
highest benefit for patients with class III obesity (BMI > 40 kg/m2 ).
PMID- 28417476
TI - Clindamycin-associated acute generalized exanthematous pustulosis.
AB - WHAT IS KNOWN AND THE OBJECTIVE: Acute generalized exanthematous pustulosis
(AGEP) is a rare, severe cutaneous reaction that usually occurs following
medication exposure. Clindamycin has rarely been linked to dermatologic side
effects, including AGEP. CASE SUMMARY: This report details the case of a patient
who developed AGEP with vancomycin and clindamycin use. After discontinuing
clindamycin, the rash improved significantly. WHAT IS NEW AND CONCLUSION: Timely
management of adverse skin reactions to antibiotics is paramount, and early
identification of the culprit agent can allow for an alternative agent to be
utilized. Clindamycin should be considered a potential causative agent for
patients with skin reactions.
PMID- 28417477
TI - A flexible family of transformation cure rate models.
AB - In this paper, we introduce a flexible family of cure rate models, mainly
motivated by the biological derivation of the classical promotion time cure rate
model and assuming that a metastasis-competent tumor cell produces a detectable
tumor mass only when a specific number of distinct biological factors affect the
cell. Special cases of the new model are, among others, the promotion time
(proportional hazards), the geometric (proportional odds), and the negative
binomial cure rate model. In addition, our model generalizes specific families of
transformation cure rate models and some well-studied destructive cure rate
models. Exact likelihood inference is carried out by the aid of the
expectationUmaximization algorithm; a profile likelihood approach is exploited
for estimating the parameters of the model while model discrimination problem is
analyzed by the aid of the likelihood ratio test. A simulation study demonstrates
the accuracy of the proposed inferential method. Finally, as an illustration, we
fit the proposed model to a cutaneous melanoma data-set. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28417478
TI - Point-of-Care Lung Sonography: An Audit of 1150 Examinations.
AB - OBJECTIVES: Point-of-care lung sonography has theoretical usefulness in numerous
diseases; however clinical indications and the impact of this technique have not
been fully investigated. We aimed to describe the current use of point-of-care
lung sonography. METHODS: A 2-year prospective observational study was performed
by pulmonologists in an Italian university hospital. Techniques, indications,
consequences of lung sonography, and barriers to the examination were analyzed.
RESULTS: A total of 1150 lung sonographic examinations were performed on 951
patients. The most common indications were diagnosis and follow-up of pleural
effusion in 361 cases (31%), evaluation of lung consolidation (322 [28%]), acute
heart failure (195 [17%]), guide to pleural procedures (117 [10%]), pneumothorax
(54 [5%]) and acute exacerbations of chronic obstructive pulmonary disease (30
[3%]). The mean duration of the examination +/- SD was 6 +/- 4 minutes. The
transducers most frequently used were convex (746 [65%]) and linear (161 [14%]),
whereas in 205 examinations (18%), both transducers were used. According to the
judgment of the caring clinician, 51% of the examinations were clinically
relevant. CONCLUSIONS: Point-of-care lung sonography performed by pulmonologists
is quick and feasible and could be widely used for different clinical indications
with a potentially high clinical impact. The widespread use of this technique may
have a relevant clinical impact in several indications.
PMID- 28417479
TI - ACCP Template for Evaluating a Clinical Pharmacist.
AB - ACCP is committed to ensuring that clinical pharmacists possess the competencies
necessary to deliver comprehensive medication management in team-based, direct
patient care environments. These competencies are divided into six essential
domains: direct patient care, pharmacotherapy knowledge, systems-based care and
population health, communication, professionalism, and continuing professional
development. The 2016 ACCP Clinical Practice Affairs Committee has developed an
evaluation tool that includes the assessable tasks of today's clinical
pharmacists that fall within each domain. This instrument can be used by
institutions, organizations, and others responsible for clinical pharmacist
performance evaluation and professional development.
PMID- 28417480
TI - Efficient Red Perovskite Light-Emitting Diodes Based on Solution-Processed
Multiple Quantum Wells.
AB - This paper reports a facile and scalable process to achieve high performance red
perovskite light-emitting diodes (LEDs) by introducing inorganic Cs into multiple
quantum well (MQW) perovskites. The MQW structure facilitates the formation of
cubic CsPbI3 perovskites at low temperature, enabling the Cs-based QWs to provide
pure and stable red electroluminescence. The versatile synthesis of MQW
perovskites provides freedom to control the crystallinity and morphology of the
emission layer. It is demonstrated that the inclusion of chloride can further
improve the crystallization and consequently the optical properties of the Cs
based MQW perovskites, inducing a low turn-on voltage of 2.0 V, a maximum
external quantum efficiency of 3.7%, a luminance of ~440 cd m-2 at 4.0 V. These
results suggest that the Cs-based MQW LED is among the best performing red
perovskite LEDs. Moreover, the LED device demonstrates a record lifetime of over
5 h under a constant current density of 10 mA cm-2 . This work suggests that the
MQW perovskites is a promising platform for achieving high performance visible
range electroluminescence emission through high-throughput processing methods,
which is attractive for low-cost lighting and display applications.
PMID- 28417481
TI - Chemical Reduction of Intrinsic Defects in Thicker Heterojunction Planar
Perovskite Solar Cells.
AB - Minimization of defects in absorber materials is essential for hybrid perovskite
solar cells, especially when constructing thick polycrystalline layers in a
planar configuration. Here, a simple methylamine solution-based additive is
reported to improve film quality with nearly an order of magnitude reduction in
intrinsic defect concentration. In the resultant film, an increase in carrier
lifetime as a result of a decrease in shallow electronic disorder is observed.
This superior crystalline film quality is further evidenced via a doubled spin
relaxation time as compared with other reports. Bearing sufficient carrier
diffusion length, a thick absorber layer (~650 nm) is implemented in planar
devices to achieve a champion power conversion efficiency of 20.02% with a
stabilized output efficiency of 19.01% under one sun illumination. This work
demonstrates a simple approach to improve hybrid perovskite film quality by
substantial reduction of intrinsic defects for wide applications in
optoelectronics.
PMID- 28417482
TI - Hall Effect in Bulk-Doped Organic Single Crystals.
AB - The standard technique to separately and simultaneously determine the carrier
concentration per unit volume (N, cm-3 ) and the mobility (MU) of doped inorganic
single crystals is to measure the Hall effect. However, this technique has not
been reported for bulk-doped organic single crystals. Here, the Hall effect in
bulk-doped single-crystal organic semiconductors is measured. A key feature of
this work is the ultraslow co-deposition technique, which reaches as low as 10-9
nm s-1 and enables us to dope homoepitaxial organic single crystals with
acceptors at extremely low concentrations of 1 ppm. Both the hole concentration
per unit volume (N, cm-3 ) and the Hall mobility (MUH ) of bulk-doped rubrene
single crystals, which have a band-like nature, are systematically observed. It
is found that these rubrene single crystals have (i) a high ionization rate and
(ii) scattering effects because of lattice disturbances, which are peculiar to
this organic single crystal.
PMID- 28417483
TI - Primary repair of complete sternal cleft associated with absent anterior
pericardium.
PMID- 28417484
TI - Well-differentiated neuroendocrine tumors in skin: Terminology and diagnostic
utility of cytokeratin 5/6 and p63.
AB - BACKGROUND: Well-differentiated neuroendocrine tumors (WDNETs) in skin include
metastases from visceral primary sites and very uncommonly, primary cutaneous
carcinoid tumors. Cutaneous WDNET may present a diagnostic challenge and in
particular can be mistaken for a benign skin adnexal tumor. In contrast to
cutaneous adnexal tumors, metastatic adenocarcinomas to the skin are cytokeratin
5/6 (CK5/6) and p63 negative in the majority of cases. It is unclear if failure
to stain with CK5/6 and p63 would be helpful in differentiating WDNETs from
cutaneous adnexal neoplasms. METHODS: We reviewed 10 cases of cutaneous WDNETs (8
cases of metastatic disease and 2 presumed primary carcinoid tumors of the skin)
and performed immunohistochemical stains for CK5/6 and p63 on all cases. RESULTS:
All 10 cases were negative with both CK5/6 and p63. CONCLUSION: Negative staining
for CK5/6 and p63 can be helpful to distinguish WDNETs from cutaneous adnexal
neoplasms. It is important to consider WDNETs in the differential diagnosis of
cutaneous adnexal neoplasms as low-grade tumors may be the first sign of
aggressive metastatic disease.
PMID- 28417485
TI - Tumor Microenvironment-Triggered Supramolecular System as an In Situ
Nanotheranostic Generator for Cancer Phototherapy.
AB - The efficacy of photosensitizers in cancer phototherapy is often limited by
photobleaching, low tumor selectivity, and tumor hypoxia. Assembling
photosensitizers into nanostructures can improve photodynamic therapy efficacy
and the safety profile of photosensitizers. Herein by employing supramolecular
assembly, enhanced theranostic capability of Mn2+ -assisted assembly of a
photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor
environment-triggered coassembly strategy is further developed to form Mn/DVDMS
nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a
highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7
cells and xenograft tumors, MnO2 /DVDMS is reduced by glutathione (GSH) and H2 O2
and reassembled into nanoDVD, which can be monitored by activated magnetic
resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH,
the production of O2 , and the formation of nanoDVD are shown to be synergistic
with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a
new avenue for cancer theranostics.
PMID- 28417486
TI - Age-specific function of alpha5beta1 integrin in microglial migration during
early colonization of the developing mouse cortex.
AB - Microglia, the immune cells of the central nervous system, take part in brain
development and homeostasis. They derive from primitive myeloid progenitors that
originate in the yolk sac and colonize the brain mainly through intensive
migration. During development, microglial migration speed declines which suggests
that their interaction with the microenvironment changes. However, the matrix
cell interactions allowing dispersion within the parenchyma are unknown.
Therefore, we aimed to better characterize the migration behavior and to assess
the role of matrix-integrin interactions during microglial migration in the
embryonic brain ex vivo. We focused on microglia-fibronectin interactions
mediated through the fibronectin receptor alpha5beta1 integrin because in vitro
work indirectly suggested a role for this ligand-receptor pair. Using 2-photon
time-lapse microscopy on acute ex vivo embryonic brain slices, we found that
migration occurs in a saltatory pattern and is developmentally regulated. Most
importantly, there is an age-specific function of the alpha5beta1 integrin during
microglial cortex colonization. At embryonic day (E) 13.5, alpha5beta1
facilitates migration while from E15.5, it inhibits migration. These results
indicate a developmentally regulated function of alpha5beta1 integrin in
microglial migration during colonization of the embryonic brain.
PMID- 28417487
TI - Reducing Interfacial Resistance between Garnet-Structured Solid-State Electrolyte
and Li-Metal Anode by a Germanium Layer.
AB - Substantial efforts are underway to develop all-solid-state Li batteries (SSLiBs)
toward high safety, high power density, and high energy density. Garnet
structured solid-state electrolyte exhibits great promise for SSLiBs owing to its
high Li-ion conductivity, wide potential window, and sufficient thermal/chemical
stability. A major challenge of garnet is that the contact between the garnet and
the Li-metal anodes is poor due to the rigidity of the garnet, which leads to
limited active sites and large interfacial resistance. This study proposes a new
methodology for reducing the garnet/Li-metal interfacial resistance by depositing
a thin germanium (Ge) (20 nm) layer on garnet. By applying this approach, the
garnet/Li-metal interfacial resistance decreases from ~900 to ~115 Omega cm2 due
to an alloying reaction between the Li metal and the Ge. In agreement with
experiments, first-principles calculation confirms the good stability and
improved wetting at the interface between the lithiated Ge layer and garnet. In
this way, this unique Ge modification technique enables a stable cycling
performance of a full cell of lithium metal, garnet electrolyte, and LiFePO4
cathode at room temperature.
PMID- 28417488
TI - Electroactive Ionic Soft Actuators with Monolithically Integrated Gold
Nanocomposite Electrodes.
AB - Electroactive ionic gel/metal nanocomposites are produced by implanting
supersonically accelerated neutral gold nanoparticles into a novel chemically
crosslinked ion conductive soft polymer. The ionic gel consists of chemically
crosslinked poly(acrylic acid) and polyacrylonitrile networks, blended with
halloysite nanoclays and imidazolium-based ionic liquid. The material exhibits
mechanical properties similar to that of elastomers (Young's modulus ~ 0.35 MPa)
together with high ionic conductivity. The fabrication of thin (~100 nm thick)
nanostructured compliant electrodes by means of supersonic cluster beam
implantation (SCBI) does not significantly alter the mechanical properties of the
soft polymer and provides controlled electrical properties and large surface area
for ions storage. SCBI is cost effective and suitable for the scaleup
manufacturing of electroactive soft actuators. This study reports the high-strain
electromechanical actuation performance of the novel ionic gel/metal
nanocomposites in a low-voltage regime (from 0.1 to 5 V), with long-term
stability up to 76 000 cycles with no electrode delamination or deterioration.
The observed behavior is due to both the intrinsic features of the ionic gel
(elasticity and ionic transport capability) and the electrical and morphological
features of the electrodes, providing low specific resistance (<100 Omega cm-2 ),
high electrochemical capacitance (~mF g-1 ), and minimal mechanical stress at the
polymer/metal composite interface upon deformation.
PMID- 28417489
TI - Management of Septic emboli in patients with infectious endocarditis.
AB - BACKGROUND AND AIM: Septic emboli (SE) associated with infectious endocarditis
(IE) can result in splenic abscesses and infectious intracranial aneurysms (IIA).
We investigated the impact of SE on patient outcomes following surgery for IE.
METHOD: From January-2000 to October-2015, all patients with surgical IE (n =
437) were evaluated for incidence and management of SE. RESULTS: Overall SE was
found in 46/437 (10.52%) patients (n = 17 spleen, 13 brain, and 16 both). No
mortality was seen in the brain emboli groups, but in the splenic abscess group
the in-hospital mortality was 8.69% (n = 4); and was associated with Age >35 (OR
= 2.63, 1.65-4.20) and congestive heart failure (OR = 14.40, 1.23-168.50).
Patients with splenic emboli had excellent mid-term outcome following discharge
(100% survival at 4-years). Splenic emboli requiring splenectomy was predicted by
a >20 mm valve vegetation (OR = 1.37, 1.056-1.77) and WBC >12000 cells/mm (OR =
5.58, 1.2-26.3). No patient with streptococcus-viridians infection had a
nonviable spleen (OR = 0.67, 0.53-0.85). Postoperative acute-kidney-injury was
higher in the splenectomy group (45.45% vs 9%) (p = 0.027). There were 6 patients
with symptomatic IIAs that required coiling/clipping which was associated with
age <30 years, (OR = 6.09, 1.10-33.55). Survival in patients with cerebral emboli
decreased to 78% at 3-4 years. Patients with both splenic and brain emboli had a
92% survival rate at 1-year and 77% at 2-4 years. CONCLUSION: Septic emboli is
common in endocarditis patients. Patients with high preoperative WBC level and
large valve vegetations require CT imaging of the spleen. Both spleen and brain
interventions in the setting of IE can be performed safely with excellent early
and mid-term outcomes.
PMID- 28417490
TI - Myocardial bridge of the left anterior descending artery.
PMID- 28417491
TI - Giant inferior vena cava aneurysm.
PMID- 28417492
TI - Editorial: CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent
(infliximab), in inflammatory bowel diseases.
PMID- 28417493
TI - Editorial: clinical benefits of vitamin D therapy in inflammatory bowel disease.
PMID- 28417494
TI - Editorial: CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent
(infliximab), in inflammatory bowel diseases - authors' reply.
PMID- 28417495
TI - Letter: chronic hepatitis C genotype 3 infection - still a hurdle toward a direct
acting anti-viral-induced HCV cure?
PMID- 28417496
TI - Editorial: accumulating data about ustekinumab in refractory Crohn's disease in
real world experience.
PMID- 28417497
TI - Editorial: importance of definition of inflammatory bowel disease and an
increased incidence in children.
PMID- 28417498
TI - Editorial: Clostridium difficile and inflammatory bowel disease - is it always a
bad combination?
PMID- 28417499
TI - Editorial: inflammatory bowel disease risk reduction after migration - are early
life events important?
PMID- 28417500
TI - Editorial: hepatitis B reactivation in patients with chronic hepatitis C treated
with direct-acting antivirals - incidence, severity of hepatitis and lessons to
learn.
PMID- 28417501
TI - D-dimer level, in association with humoral responses, negatively correlates with
survival of porcine islet grafts in non-human primates with immunosuppression.
AB - BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft
survival in non-human primates (NHPs) after porcine islet transplantation (PITx),
but their success rates vary. To understand the mechanism of graft loss, we
investigated the relationships between graft survival and humoral or inflammatory
responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from
adult wild-type pigs were intraportally transplanted into streptozotocin-induced
diabetic rhesus monkeys. Three monkeys received an IS regimen without anti-CD154
monoclonal antibody (mAb, transplant [Tpl]-control) and 11 received IS with anti
CD154 mAb (Tpl-aCD154). Blood samples were obtained weekly from the recipients
until graft function ceased and weekly from three healthy monkeys (non-Tpl
control) for 6 months. Levels of D-dimer, C-reactive protein (CRP), and anti
Galalpha1,3Gal (Gal) IgG, IgG1, IgG2, and IgM were measured. Liver biopsy
sections were immunostained for fibrin, insulin, and human CD31. RESULTS: Tpl
control monkeys had higher time-weighted average levels (levelstwavrg ) of
Deltaanti-Gal IgG (Delta, difference from level at day 0) and D-dimer than Tpl
aCD154 or non-Tpl-control. The levelstwavrg of Deltaanti-Gal IgG, IgG1, IgG2, and
IgM did not differ between Tpl-aCD154 and non-Tpl-control. The levelstwavrg of D
dimer and Deltaanti-Gal IgG2 negatively correlated with graft survival. Liver
biopsy sections revealed many spots of fibrin deposition inside islet grafts that
were well vascularized by human CD31-positive cells. Level of D-dimer positively
correlated with Deltaanti-Gal IgG1 in Tpl-control and with Deltaanti-Gal IgG2 in
Tpl-aCD154. CONCLUSIONS: Intravascular coagulation, in association with immune
responses against xenografts, may partly contribute to loss of islet grafts in
NHPs after PITx.
PMID- 28417502
TI - A Quinonoid-Imine-Enriched Nanostructured Polymer Mediator for Lithium-Sulfur
Batteries.
AB - The reversible formation of chemical bonds has potential for tuning multi
electron redox reactions in emerging energy-storage applications, such as lithium
sulfur batteries. The dissolution of polysulfide intermediates, however, results
in severe shuttle effect and sluggish electrochemical kinetics. In this study,
quinonoid imine is proposed to anchor polysulfides and to facilitate the
formation of Li2 S2 /Li2 S through the reversible chemical transition between
protonated state (?NH+ ?) and deprotonated state (?N?). When serving as the
sulfur host, the quinonoid imine-doped graphene affords a very tiny shuttle
current of 2.60 * 10-4 mA cm-2 , a rapid redox reaction of polysulfide, and
therefore improved sulfur utilization and enhanced rate performance. A high areal
specific capacity of 3.72 mAh cm-2 is achieved at 5.50 mA cm-2 on the quinonoid
imine-doped graphene based electrode with a high sulfur loading of 3.3 mg cm-2 .
This strategy sheds a new light on the organic redox mediators for reversible
modulation of electrochemical reactions.
PMID- 28417503
TI - Robotic resection of giant left ventricular myxoma causing outflow tract
obstruction.
AB - We report a 38-year-old female, who presented with progressive dyspnea and
fatigue. Echocardiography revealed a giant and freely mobile left ventricular
myxoma causing left ventricular outflow tract (LVOT) obstruction. The patient
underwent totally endoscopic robotic excision of a giant left ventricular myxoma.
The tumor was completely removed through the mitral valve orifice with a left
atriotomy incision.
PMID- 28417504
TI - The coping function of mental disorder symptoms: is it to be considered when
developing diagnostic criteria for behavioural addictions?
PMID- 28417505
TI - 300% Enhancement of Carrier Mobility in Uniaxial-Oriented Perovskite Films Formed
by Topotactic-Oriented Attachment.
AB - Organic-inorganic perovskites with intriguing optical and electrical properties
have attracted significant research interests due to their excellent performance
in optoelectronic devices. Recent efforts on preparing uniform and large-grain
polycrystalline perovskite films have led to enhanced carrier lifetime up to
several microseconds. However, the mobility and trap densities of polycrystalline
perovskite films are still significantly behind their single-crystal
counterparts. Here, a facile topotactic-oriented attachment (TOA) process to grow
highly oriented perovskite films, featuring strong uniaxial-crystallographic
texture, micrometer-grain morphology, high crystallinity, low trap density (~4 *
1014 cm-3 ), and unprecedented 9 GHz charge-carrier mobility (71 cm2 V-1 s-1 ),
is demonstrated. TOA-perovskite-based n-i-p planar solar cells show minimal
discrepancies between stabilized efficiency (19.0%) and reverse-scan efficiency
(19.7%). The TOA process is also applicable for growing other state-of-the-art
perovskite alloys, including triple-cation and mixed-halide perovskites.
PMID- 28417506
TI - The effect of intraoperative hypothermia upon blood transfusion needs and length
of stay among gastrointestinal system cancer surgery.
AB - This cross-sectional study was performed to evaluate the relationship between
intraoperative body temperature and the need for blood transfusion and length of
stay in the post-anaesthetic care unit (PACU) or in the intensive care unit (ICU)
among 79 patients undergoing elective oncology surgery of the digestive system.
There was a statistically significant correlation between a lower temperature
during surgery and medical diagnosis (p = .009), the use of bupivacaine
anaesthesia (p = .016), anaesthesia time (p = .003) and anaesthesia type (p =
.033), surgery time (p = .021) and surgery type (p = .002), volumes infused
during the intraoperative period (p = .006), admission to the ICU (p = .032) and
length of stay in PACU (p = .029). The lower the temperature when the patient is
admitted to the operating room, the lower the temperature during the procedure (p
? .001). There was no association between the body temperature of patients and
blood transfusion (p = .619). Hypothermia was associated with increased length of
stay in the PACU, but was not associated with the need for blood transfusion
during the intra- and postoperative periods. The use of preoperative passive
warming methods allows patients to reach the operating room hypothermic.
PMID- 28417507
TI - Understanding the roots of health inequalities requires new methods.
PMID- 28417508
TI - Effectiveness of semi-permeable dressings to treat radiation-induced skin
reactions. A systematic review.
AB - The aim of this systematic review is to assess the available evidence concerning
the effectiveness of semi-permeable dressings, on the full range of skin
reactions, related to radiation therapy in cancer patients, from local erythema
to moist desquamation, including subjective symptoms such as pain, discomfort,
itchiness, burning and the effect on daily life activities. The bibliographic
search was carried out looking for Randomised Clinical Trials (RCTs) indexed in
PubMed, Cinhal, Cochrane plus and Biblioteca Nacional de Salud, published in the
English and Spanish language, between 2010 and 2015. Data extraction and
evaluation of study quality was undertaken by peer reviewers using the Critical
Appraisal Skills Programme (CASP). Of 181 studies, nine full texts were assessed.
Finally, six RCT were included in the final synthesis: three analysed the
application of Mepilex(r) Lite in breast cancer and head & neck cancer; one
evaluated the application of Mepitel(r) Film in breast cancer; and two assessed
the use of silver nylon dressings in breast cancer and in patients with lower
gastrointestinal cancer. The results show that semi-permeable dressings are
beneficial in the management of skin toxicity related to radiation therapy.
However, rigorous trials showing stronger evidence are needed.
PMID- 28417509
TI - A biomolecular recognition approach for the functionalization of cellulose with
gold nanoparticles.
AB - Materials with new and improved functionalities can be obtained by modifying
cellulose with gold nanoparticles (AuNPs) via the in situ reduction of a gold
precursor or the deposition or covalent immobilization of pre-synthesized AuNPs.
Here, we present an alternative biomolecular recognition approach to
functionalize cellulose with biotin-AuNPs that relies on a complex of 2
recognition elements: a ZZ-CBM3 fusion that combines a carbohydrate-binding
module (CBM) with the ZZ fragment of the staphylococcal protein A and an anti
biotin antibody. Paper and cellulose microparticles with AuNPs immobilized via
the ZZ-CBM3:anti-biotin IgG supramolecular complex displayed an intense red
color, whereas essentially no color was detected when AuNPs were deposited over
the unmodified materials. Scanning electron microscopy analysis revealed a
homogeneous distribution of AuNPs when immobilized via ZZ-CBM3:anti-biotin IgG
complexes and aggregation of AuNPs when deposited over paper, suggesting that
color differences are due to interparticle plasmon coupling effects. The approach
could be used to functionalize paper substrates and cellulose nanocrystals with
AuNPs. More important, however, is the fact that the occurrence of a biomolecular
recognition event between the CBM-immobilized antibody and its specific, AuNP
conjugated antigen is signaled by red color. This opens up the way for the
development of simple and straightforward paper/cellulose-based tests where
detection of a target analyte can be made by direct use of color signaling.
PMID- 28417510
TI - Morphology Tunable Hybrid Carbon Nanosheets with Solvatochromism.
AB - The tunable photoluminescence of carbon-based nanomaterials has received much
attention for a wide range of applications. Herein, a unique, broad
solvatochromic hybrid carbon nanosheet (CNS) synthesized through the hydrothermal
carbonization of molecular precursors exploiting graphene oxide as a template is
reported, resulting in the formation of clusters of carbon nanorings on the
surface of graphene-oxide nanosheets. Under UV and visible-light excitation, the
hybrid CNS exhibits tunable emission spanning the wide range of colors in a
series of solvents with different polarities. This interesting spectroscopic
behavior is found to originate from hydrogen-bonding interactions between CNS and
solvents, which eventually induce the morphological transition of CNS from 2D
sheets to 3D crumpled morphologies, affecting the lifetimes of emissive states.
This novel soft carbon nanostructure may open up a new possibility in tailoring
the photophysical properties of carbon nanomaterials.
PMID- 28417511
TI - Algal supplementation of vegetarian eating patterns improves plasma and serum
docosahexaenoic acid concentrations and omega-3 indices: a systematic literature
review.
AB - BACKGROUND: Vegetarians are likely to have lower intakes of preformed
docosahexaenoic acid (DHA) than omnivorous populations who consume fish and
animal products. As such, vegetarian populations have omega-3 indices up to 60%
lower than those who consume marine products. Algae, the primary producer of DHA
in the marine food chain, offer an alternative source of DHA for those who do not
consume marine or animal products. This systematic review aims to examine the
evidence for the relationship between supplementation with algal forms of DHA and
increased DHA concentrations in vegetarian populations. METHODS: The SCOPUS,
Science Direct and Web of Science scientific databases were searched to identify
relevant studies assessing the effect of algal DHA consumption by vegetarian
(including vegan) populations. RESULTS: Four randomised controlled trials and two
prospective cohort studies met the inclusion criteria. All included studies
reported algal sources of DHA significantly improve DHA concentrations (including
plasma, serum, platelet and red blood cell fractions), as well as omega-3
indices, in vegetarian populations. An evident time or dose response was not
apparent given the small number of studies to date. CONCLUSIONS: Future studies
should address long chain n-3 polyunsaturated fatty acid deficiencies in
vegetarian populations using algal DHA and explore the potential physiological
and health improvements in these individuals.
PMID- 28417512
TI - Na2 Ti3 O7 @N-Doped Carbon Hollow Spheres for Sodium-Ion Batteries with Excellent
Rate Performance.
AB - Uniform Na2 Ti3 O7 hollow spheres assembled from N-doped carbon-coated ultrathin
nanosheets are synthesized. A unique multilayer structure of nanosheets is
presumed to significantly reduce energy consumption during the diffusion process
of sodium ions, while the carbon-coated structure can increase the overall
conductivity. The as-prepared sample used as an anode in sodium-ion batteries
exhibits the best rate performance ever reported for Na2 Ti3 O7 , delivering more
than 60 mAh g-1 after 1000 continuous cycles at the high rate of 50 C, which was
achieved due to its unique structure.
PMID- 28417513
TI - Repair of a coronary artery aneurysm in close proximity to the left main trunk.
PMID- 28417514
TI - Enlarged Cavum Septi Pellucidi and Vergae in the Fetus: A Cause for Concern.
AB - OBJECTIVES: To investigate fetal cases identified at our institution to determine
whether an enlarged cavum septi pellucidi or cavum vergae is associated with
other fetal abnormalities and whether its presence warrants more detailed
investigation of the fetus. METHODS: In a retrospective study, 15 high- and low
risk patients undergoing prenatal sonography who had an enlarged cavum septi
pellucidi or cavum vergae identified were reviewed. Data were collected for the
sonographic study indication, gestation age at diagnosis of a prominent cavum,
and associated anomalies. Follow-up outcome data regarding further imaging,
karyotype, diagnosis of brain anomaly, and associated congenital abnormalities
were obtained. RESULTS: Fifteen patients met the inclusion criteria. Nine
patients were identified as having a prominent cavum septi pellucidi, and 6 were
identified as having a prominent cavum vergae. The mean gestational age +/- SD
was 22.7 +/- 5.9 weeks. Eleven patients made it to delivery. Of the 15 patients,
4 were thought to have trisomy 21, and 13 had congenital anomalies. Outcomes
included 10 major adverse outcomes, 4 cases with normal development or minor
abnormalities, and 1 lost to follow-up. An isolated dilated cavum on prenatal
sonography was seen in 5 cases: 1 with lissencephaly on a neonatal examination, 3
premature deliveries (1 demise, 1 hospice, and 1 normal), and 1 unknown.
CONCLUSIONS: Our cohort had many associated clinical anomalies: 3 confirmed
trisomy 21 and 1 probable trisomy 21, 2 genetic disorders, and 10 major adverse
outcomes, 5 of which were grave. Although we studied a small cohort, we conclude
that an enlarged cavum septi pellucidi or cavum vergae warrants consideration of
genetic counseling, which may include noninvasive prenatal testing (cell-free
DNA), amniocentesis with microarray testing, or both.
PMID- 28417515
TI - Do maternal depression and anxiety influence children's oral health-related
quality of life?
AB - OBJECTIVE: This study aimed to investigate the influence of depressive and
anxiety symptoms in young mothers on their perception in relation to their
children's oral health-related quality of life (COHRQoL). METHODS: This cross
sectional study was carried out in Pelotas, Southern Brazil, and it was nested in
a cohort of adolescent mothers having their prenatal care in public health
service, starting in 2008. When the children were aged 24-36 months, they and
their mothers were interviewed and submitted to clinical examination by a trained
team. Socioeconomic, educational, behavioural and psychological assessments were
collected in the interview and oral examination investigated caries and gingival
bleeding (in mothers) and caries and dental trauma (in children). Maternal
perception of impact on COHRQoL was evaluated by Early Childhood Oral Health
Impact Scale (ECOHIS). The outcome in the present study was the occurrence of
impact on COHRQoL (ECOHIS>=2), that is the presence of at least one ECOHIS item
reported as occasionally (score 2), often (score 3) or very often (score 4).
Analysis was conducted using Poisson regression with robust variance and obtained
prevalence ratios (PR) and respective 95% confidence intervals (CI). RESULTS:
This study comprised 537 mother-child dyads. After adjustment, higher scores of
COHRQoL remained significantly associated with depressive symptoms (PR=1.80, 95%
CI: 1.36-2.38) and maternal anxiety symptoms (PR=2.28, 95% CI: 1.72-3.00).
Mothers with anxiety symptoms or depressive symptoms had a prevalence of impact
91% higher when compared with mothers without any symptoms (PR=1.91; CI 95% 1.35
2.68), and mothers with both symptoms had almost 2.5 times higher risk of
perception of negative impact on COHRQoL (PR=2.48; CI 95% 1.78-3.45). CONCLUSION:
Poorer COHRQoL was associated with maternal depression and anxiety symptoms.
PMID- 28417516
TI - Discovering What Matters: Interrogating Clinician Responses to Ethics
Consultation.
AB - Against the background assumptions that (a) knowing what clinical ethics
consultation represents to those with whom ethics consultants work most closely
is a necessary component for being responsible in the practice of ethics
consultation, and (b) the complexities of soliciting and understanding colleague
evaluations require another inherent responsibility for the methods by which
ethics consultations are evaluated, in this article we report our experience
soliciting, analyzing, and trying to understand retrospective evaluations of our
Clinical Ethics Consultation Service. These evaluations were collected through a
quality assessment effort at our institution. Drawing from the qualitative
elements of our survey instrument, we describe unexpected variations among the
requests for ethics consultation and the retrospective reports from those
colleagues making the requests. Focusing on just one aspect - the reason for
request - raised several core questions about how we should evaluate those
retrospective reports, what could be learned from the differences that we were
now encountering, and what we could learn about the process of evaluating our
practices. Working through these questions, we suggest several issues to consider
in ongoing efforts to describe and evaluate clinical ethics consultation: the
role of time and memory in evaluating retrospective evaluations, the importance
of attending to the language of moral shift or disruption with which our
colleagues describe their experiences, and how to understand the role of ethics
consultation in creating 'moral space' (a la Margaret Urban Walker's conception)
for colleagues to process their moral experiences.
PMID- 28417517
TI - Evaluating Clinical Ethics Support: A Participatory Approach.
AB - The current process towards formalization within evaluation research, in
particular the use of pre-set standards and the focus on predefined outcomes,
implies a shift of ownership from the people who are actually involved in real
clinical ethics support services (CESS) in a specific context to external
stakeholders who increasingly gain a say in what 'good CESS' should look like.
The question is whether this does justice to the insights and needs of those who
are directly involved in actual CESS practices, be it as receivers or providers.
We maintain that those actually involved in concrete CESS practices should also
be involved in its evaluation, not only as respondents, but also in setting the
agenda of the evaluation process and in articulating the criteria by which CESS
is evaluated. Therefore, we propose a participatory approach to CESS evaluation.
It focuses on (1) the concrete contexts in which CESS takes place, (2) reflective
and dialogical learning processes, and (3) how to be democratic and inclusive. In
particular, this approach to CESS evaluation is akin to realist evaluation,
dialogical evaluation, and responsive evaluation. An example of a participatory
approach to evaluating CESS is presented and some critical issues concerning this
approach are discussed.
PMID- 28417518
TI - What Outcomes do Dutch Healthcare Professionals Perceive as Important Before
Participation in Moral Case Deliberation?
AB - BACKGROUND: There has been little attention paid to research on the outcomes of
clinical ethics support (CES) or critical reflection on what constitutes a good
CES outcome. Understanding how CES users perceive the importance of CES outcomes
can contribute to a better understanding, use of and normative reflection on CES
outcomes. OBJECTIVE: To describe the perceptions of Dutch healthcare
professionals on important outcomes of moral case deliberation (MCD), prior to
MCD participation, and to compare results between respondents. METHODS: This
mixed-methods study used both the Euro-MCD instrument and semi-structured
interviews. Healthcare professionals who were about to implement MCD were
recruited from nursing homes, hospitals, psychiatry and mentally disabled care
institutions. RESULTS: 331 healthcare professionals completed the Euro-MCD
instrument, 13 healthcare professionals were interviewed. The outcomes perceived
as most important were 'more open communication', 'better mutual understanding',
'concrete actions', 'see the situation from different perspectives', 'consensus
on how to manage the situation' and 'find more courses of action'. Interviewees
also perceived improving quality of care, professionalism and the organization as
important. Women, nurses, managers and professionals in mentally disabled care
rated outcomes more highly than other respondents. CONCLUSIONS: Dutch healthcare
professionals perceived the MCD outcomes related to collaboration as most
important. The empirical findings can contribute to shared ownership of MCD and a
more specific use of MCD in different contexts. They can inform international
comparative research on different CES types and contribute to normative
discussions concerning CES outcomes. Future studies should reflect upon important
MCD outcomes after having experienced MCD.
PMID- 28417519
TI - Methodological Reflections on the Contribution of Qualitative Research to the
Evaluation of Clinical Ethics Support Services.
AB - This article describes a process of developing, implementing and evaluating a
clinical ethics support service intervention with the goal of building up a
context-sensitive structure of minimal clinical-ethics in an oncology department
without prior clinical ethics structure. Scholars from different disciplines have
called for an improvement in the evaluation of clinical ethics support services
(CESS) for different reasons over several decades. However, while a lot has been
said about the concepts and methodological challenges of evaluating CESS up to
the present time, relatively few empirical studies have been carried out. The aim
of this article is twofold. On the one hand, it describes a process of
development, modifying and evaluating a CESS intervention as part of the ETHICO
research project, using the approach of qualitative-formative evaluation. On the
other hand, it provides a methodological analysis which specifies the
contribution of qualitative empirical methods to the (formative) evaluation of
CESS. We conclude with a consideration of the strengths and limitations of
qualitative evaluation research with regards to the evaluation and development of
context sensitive CESS. We further discuss our own approach in contrast to rather
traditional consult or committee models.
PMID- 28417520
TI - Integrating Theory and Data in Evaluating Clinical Ethics Support. Still a Long
Way to Go.
PMID- 28417521
TI - Evaluating the Quality of the Deliberation in Moral Case Deliberations: A Coding
Scheme.
AB - Moral Case Deliberation (MCD) is an up and coming form of ethics support wherein
clinical professionals deliberate about moral questions they face in their work.
So far, it has been unclear what quality of deliberation in MCD is entailed and
how to evaluate this quality. This article proposes a coding scheme that fits the
theoretical background of MCD and allows researchers to evaluate the quality of
the deliberation in MCDs. We consider deliberation in MCD to be of good quality
when participants enrich their own understanding of a case by being exposed to
the viewpoints of others. In order to have such an enriching effect, the
deliberation in an MCD ought to involve different kinds of arguments from the
perspectives of different stakeholders and in favour of different resolutions to
the case; and the process of deliberation ought to be critical but constructive.
PMID- 28417522
TI - Determinants of large drain losses early after pediatric liver transplantation.
AB - The goal of this study was to evaluate postoperative ascites to correlate it with
graft dysfunction and other complications. We therefore reviewed the files of
patients transplanted between 2009 and 2014 to correlate drain losses with
indication, patient and organ size, PELD, graft type, GRWR, NRBW, NGWD, cold
ischemia time, histologically proven graft dysfunction, and surgical
complications. Of 120 LTs in 104 patients, 48 (40%) were complicated by graft
dysfunction, 43 (36%) by surgical complications, and 25 (21%) by cellular
rejection. Large drain losses correlated with younger age (P=.05), graft
dysfunction (P<.01), surgical complications (P<.01), chylous ascites (P=.05);
there was no association with PELD, GRWR, NRBW, or NGWD. Graft dysfunction was
predicted by >20 mL/kg/d of ascites at age 0-2 years (AUROC 0.671), and >10
mL/kg/d above 2 years (AUROC 0.710). The measurement of drain losses after
pediatric LT could be used as a non-invasive marker of graft dysfunction. Younger
recipients tend to develop larger amounts of ascites, and its persistence is
associated with early complications.
PMID- 28417523
TI - Straightforward Synthesis of 2- and 2,8-Substituted Tetracenes.
AB - A simple regiospecific route to otherwise problematic substituted tetracenes is
described. The diverse cores (E)-1,2-Ar1 CH2 (HOCH2 )C=C(CH2 OH)I (Ar1 =Ph, 4
MePh, 4-MeOPh, 4-FPh) and (E)-1,2-I(HOCH2 )C=C(CH2 OH)I, accessed from ultra-low
cost HOCH2 C=CCH2 OH at multi-gram scales, allow the synthesis of diol libraries
(E)-1,2-Ar1 CH2 (HOCH2 )C=C(CH2 OH)CH2 Ar2 (Ar2 =Ph, 4-MePh, 4-iPrPh, 4-MeOPh, 4
FPh, 4-BrPh, 4-biphenyl, 4-styryl; 14 examples) by efficient Negishi coupling.
Copper-catalysed aerobic oxidation cleanly provides dialdehydes (E)-1,2-Ar1 CH2
(CHO)C=C(CHO)CH2 Ar2 , which in many cases undergo titanium(IV) chloride-induced
double Bradsher closure, providing a convenient method for the synthesis of
regiochemically and analytically pure tetracenes (12 examples). The sequence is
typically chromatography-free, scalable, efficient and technically simple to
carry out.
PMID- 28417524
TI - Biofilms of Candida spp. from the ocular conjunctiva of horses with reduced azole
susceptibility: a complicating factor for the treatment of keratomycosis?
AB - OBJECTIVES: This study aimed to assess the biofilm-forming ability of Candida
spp. from the ocular conjunctiva of horses and to investigate the antifungal
susceptibility of these biofilms. PROCEDURES: Initially, the biofilm-forming
ability of 15 strains was assessed by crystal violet staining, which reveals the
fungal biomass adhered to the polystyrene plates, and scanning electron
microscopy. Then, the minimum inhibitory concentrations (MICs) of amphotericin B,
fluconazole, itraconazole, and caspofungin were initially determined against
strains in planktonic form. Afterward, antifungal susceptibility of mature
biofilms was evaluated by exposing them to 10 * MIC and 50 * MIC of the tested
drugs, followed by the assessment of their metabolic activity, using the
oxidoreduction indicator XTT. Results were analyzed through ANOVA and Tukey's
post-test, and P-values below 5% led to significant conclusions. RESULTS: Eight
strains produced biofilms and were classified as strong (1/15), moderate (3/15)
and weak (4/15) producers, according to the amount of crystal violet retained by
the adhered fungal biomass. Biofilm metabolic activity of one C. tropicalis did
not decrease after exposure to the tested antifungals, while biofilm metabolic
activity of five strains was reduced by amphotericin B, but not the other drugs.
One C. parapsilosis sensu stricto and one C. glabrata showed significant
reduction in biofilm metabolic activity after exposure to fluconazole,
itraconazole, and caspofungin, but not amphotericin B. CONCLUSIONS: The results
demonstrate that Candida from the ocular conjunctiva of horses can pose as a risk
to animal health as they are capable of forming biofilms, which are commonly
involved in fungal keratitis.
PMID- 28417525
TI - Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm.
AB - Although metformin has been used for over 60 years, the balance between the
drug's beneficial and adverse effects is still subject to debate. Following an
analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA)
are reported in the literature, the present article reviews the pitfalls to be
avoided when assessing the purported association between metformin and lactic
acidosis. By starting from pathophysiological considerations, we propose a new
paradigm for lactic acidosis in metformin-treated patients. Metformin therapy
does not necessarily induce metformin accumulation, just as metformin
accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia
does not necessarily induce lactic acidosis. In contrast to the conventional
view, MALA probably accounts for a smaller proportion of cases than either
metformin-unrelated lactic acidosis or metformin-induced lactic acidosis. Lastly,
this review highlights the need for substantial improvements in the reporting of
cases of lactic acidosis in metformin-treated patients. Accordingly, we propose a
check-list as a guide to clinical practice.
PMID- 28417526
TI - Response to letter to editor titled "Para-Hisian Pacing Maneuver: A Pitfall in
the Pitfall".
PMID- 28417527
TI - Effects of dapagliflozin on insulin-requirement, glucose excretion and beta
hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1
diabetes.
AB - Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore,
this placebo-controlled, randomized, crossover study was set up to assess the
safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin
(DAPA) as add-on to insulin in relationship to HbA1c in youth. A total of 33
youths (14 males, median age 16 years, diabetes duration 8 years) were included
and stratified into 3 baseline HbA1c categories (<7.5%, 7.5%-9.0% or >9.0; n = 11
each). During the study period of 24 hours, intravenous insulin administration
and glucose-infusion kept blood glucose levels at 160 to 220 mg/dL. DAPA reduced
mean insulin dose by 13.6% ( P < .0001 by ANOVA) and increased urinary glucose
excretion by 610% (143.4 vs 22.4 g/24 h; P < .0001), both irrespective of
baseline HbA1c. Six independent episodes in 6 patients with plasma beta
hydroxybutyrate levels between >=0.6 and <1.0 mmol/L were observed after liquid
meal challenges, 5 episodes in the DAPA group and 1 in the placebo group. This
study provides a proof-of-concept, irrespective of preexisting HbA1c levels, for
adjunct SGLT2-inhibitor therapy in the paediatric age group by lowering insulin
dose and increasing glucose excretion.
PMID- 28417528
TI - Attribution of seasonal leaf area index trends in the northern latitudes with
"optimally" integrated ecosystem models.
AB - Significant increases in remotely sensed vegetation indices in the northern
latitudes since the 1980s have been detected and attributed at annual and growing
season scales. However, we presently lack a systematic understanding of how
vegetation responds to asymmetric seasonal environmental changes. In this study,
we first investigated trends in the seasonal mean leaf area index (LAI) at
northern latitudes (north of 30 degrees N) between 1982 and 2009 using three
remotely sensed long-term LAI data sets. The most significant LAI increases
occurred in summer (0.009 m2 m-2 year-1 , p < .01), followed by autumn (0.005
m2 m-2 year-1 , p < .01) and spring (0.003 m2 m-2 year-1 , p < .01). We then
quantified the contribution of elevating atmospheric CO2 concentration (eCO2 ),
climate change, nitrogen deposition, and land cover change to seasonal LAI
increases based on factorial simulations from 10 state-of-the-art ecosystem
models. Unlike previous studies that used multimodel ensemble mean (MME), we used
the Bayesian model averaging (BMA) to optimize the integration of model ensemble.
The optimally integrated ensemble LAI changes are significantly closer to the
observed seasonal LAI changes than the traditional MME results. The BMA factorial
simulations suggest that eCO2 provides the greatest contribution to increasing
LAI trends in all seasons (0.003-0.007 m2 m-2 year-1 ), and is the main factor
driving asymmetric seasonal LAI trends. Climate change controls the spatial
pattern of seasonal LAI trends and dominates the increase in seasonal LAI in the
northern high latitudes. The effects of nitrogen deposition and land use change
are relatively small in all seasons (around 0.0002 m2 m-2 year-1 and 0.0001
0.001 m2 m-2 year-1 , respectively). Our analysis of the seasonal LAI responses
to the interactions between seasonal changes in environmental factors offers a
new perspective on the response of global vegetation to environmental changes.
PMID- 28417529
TI - Cardiovascular risk management in rheumatoid arthritis: A large gap to close.
AB - OBJECTIVE: Rheumatoid arthritis (RA) portends significant cardiovascular
morbidity and mortality. We therefore determined how often rheumatologists
screened for and managed cardiovascular risk factors in RA patients, and the
barriers to doing so. METHODS: We examined 300 patient charts from 10 university
affiliated rheumatology practices, to ascertain if they had been screened,
treated and/or referred over a 3-year period. We subsequently distributed a
national survey to Canadian rheumatologists to elucidate challenges in performing
optimal cardiovascular risk modification. RESULTS: Most patients were screened
for hypertension. Forty-one per cent were found to be hypertensive; however, the
majority of these patients were neither treated nor referred to another provider
for management. A small minority of patients were screened for diabetes and/or
hyperlipidaemia, and these were usually not addressed if abnormal. Men were
referred more frequently than women. Consistent with these findings, the majority
of rheumatologists from the national survey felt that they did not manage
cardiovascular risk adequately; 79.4% cited a lack of time as a major barrier,
and 82.5% felt that it should be managed by the primary care provider.
CONCLUSION: There is marked underdiagnosis and undertreatment of cardiac risk in
RA. Several major barriers exist, including lack of time. Most rheumatologists
feel that this aspect of care is the responsibility of primary care physicians.
PMID- 28417531
TI - Desmoid-type fibromatosis in a boy with Down syndrome.
AB - Patients with Down syndrome (DS) have a markedly higher incidence of childhood
leukemia, but a lower incidence of most solid tumors, compared with age-matched
euploid individuals. Trisomy 21 might be protective against tumorigenesis because
of several tumor suppressive mechanisms. Desmoid-type fibromatosis (DF) is a rare
monoclonal, fibroblastic proliferation characterized by a variable clinical
course. In recent reports, almost all cases of DF involved genomic alterations
associated with activation of the Wnt/beta-catenin pathway. Here, we report the
case of a boy with DS who developed DF without activation of the Wnt/beta-catenin
pathway. To the best of our knowledge, this is the first case of DS involving DF.
PMID- 28417530
TI - Rho GDP-dissociation inhibitor alpha is a potential prognostic biomarker and
controls telomere regulation in colorectal cancer.
AB - Rho GDP-dissociation inhibitor alpha (RhoGDIalpha) is an essential regulator for
Rho GTPases. Although RhoGDIalpha may serve as an oncogene in colorectal cancer
(CRC), the underlying mechanism is still unclear. We investigated the function,
mechanism, and clinical significance of RhoGDIalpha in CRC progression. We
founded that downregulation of RhoGDIalpha repressed CRC cell proliferation,
motility, and invasion. Overexpression of RhoGDIalpha increased DNA damage
response signals at telomeres, and led to telomere shortening in CRC cells, also
being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that
RhoGDIalpha could promote telomeric repeat factor 1 (TRF1) expression through the
phosphatidylinositol 3-kinase-protein kinase B signal pathway. Moreover,
RhoGDIalpha protein levels were strongly correlated with TRF1 in CRC tissues. A
cohort of 297 CRC samples validated the positive relationship between RhoGDIalpha
and TRF1, and revealed that RhoGDIalpha and TRF1 levels were negatively
associated with CRC patients' survival. Taken together, our results suggest that
RhoGDIalpha regulate TRF1 and telomere length and may be novel prognostic
biomarkers in colorectal cancer.
PMID- 28417532
TI - Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic
associations in patients with type 1 diabetes and type 2 diabetes.
AB - We investigated non-alcoholic fatty liver disease (NAFLD) prevalence and its
metabolic associations in patients with type 1 diabetes (T1D), and in insulin
naive and insulin-treated patients with type 2 diabetes (T2D). Baseline data from
patients who had liver fat content (LFC) evaluated by magnetic resonance imaging
in four phase 3 studies of basal insulin peglispro (BIL) were analysed.
Associations of NAFLD with clinical characteristics, glycaemic control and
diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC >= 6%)
was low in T1D (8.8%) but high in T2D, with greater prevalence in insulin-naive
(75.6%) vs insulin-treated (61.7%) T2D patients. LFC (mean +/- SD) was higher in
T2D patients (insulin-naive, 13.0% +/- 8.4%; insulin-treated, 10.2% +/- 7.8%)
than in T1D patients (3.2% +/- 3.2%). In T2D, NAFLD was associated with several
markers of insulin resistance. In all three populations, there was an absence of
association of HbA1c with LFC, but insulin doses were higher in patients with
NAFLD.
PMID- 28417533
TI - Split tasks of asymmetric nucleotide-binding sites in the heterodimeric ABC
exporter EfrCD.
AB - Many heterodimeric ATP-binding cassette (ABC) exporters evolved asymmetric ATP
binding sites containing a degenerate site incapable of ATP hydrolysis due to
noncanonical substitutions in conserved sequence motifs. Recent studies revealed
that nucleotide binding to the degenerate site stabilizes contacts between the
nucleotide-binding domains (NBDs) of the inward-facing transporter and regulates
ATP hydrolysis at the consensus site via allosteric coupling mediated by the D
loops. However, it is unclear whether nucleotide binding to the degenerate site
is strictly required for substrate transport. In this study, we examined the
functional consequences of a systematic set of mutations introduced at the
degenerate and consensus site of the multidrug efflux pump EfrCD of Enterococcus
faecalis. Mutating motifs which differ among the two ATP-binding sites (Walker B,
switch loop, and ABC signature) or which are involved in interdomain
communication (D-loop and Q-loop) led to asymmetric results in the functional
assays and were better tolerated at the degenerate site. This highlights the
importance of the degenerate site to allosterically regulate the events at the
consensus site. Mutating invariant motifs involved in ATP binding and NBD closure
(A-loop and Walker A) resulted in equally reduced transport activities,
regardless at which ATP-binding site they were introduced. In contrast to
previously investigated heterodimeric ABC exporters, mutation of the degenerate
site Walker A lysine completely inactivated ATPase activity and substrate
transport, indicating that ATP binding to the degenerate site is essential for
EfrCD. This study provides novel insights into the split tasks of asymmetric ATP
binding sites of heterodimeric ABC exporters.
PMID- 28417534
TI - Cardiac function and cognition in older community-dwelling cardiac patients.
AB - BACKGROUND: Cognitive deficits have been reported in older cardiac patients. An
underlying mechanism for these findings may be reduced cardiac function. The
relationship between cardiac function as represented by different
echocardiographic measures and different cognitive function domains in older
cardiac patients remains unknown. METHODS: An older (>=70 years) heterogeneous
group of 117 community-dwelling cardiac patients under medical supervision by a
cardiologist underwent thorough echocardiographic assessment including left
ventricular ejection fraction, cardiac index, left atrial volume index, left
ventricular mass index, left ventricular diastolic function, and valvular
calcification. During a home visit, a neuropsychological assessment was performed
within 7.1 +/- 3.8 months after echocardiographic assessment; the
neuropsychological assessment included three subtests of a word-learning test
(encoding, recall, recognition) to examine one memory function domain and three
executive function tests, including digit span backwards, Trail Making Test B
minus A, and the Stroop colour-word test. RESULTS: Regression analyses showed no
significant linear or quadratic associations between any of the echocardiographic
functions and the cognitive function measures. CONCLUSIONS: None of the
echocardiographic measures as representative of cardiac function was correlated
with memory or executive function in this group of community-dwelling older
cardiac patients. These findings contrast with those of previous studies.
PMID- 28417536
TI - Stretchable and Soft Electronics using Liquid Metals.
AB - The use of liquid metals based on gallium for soft and stretchable electronics is
discussed. This emerging class of electronics is motivated, in part, by the new
opportunities that arise from devices that have mechanical properties similar to
those encountered in the human experience, such as skin, tissue, textiles, and
clothing. These types of electronics (e.g., wearable or implantable electronics,
sensors for soft robotics, e-skin) must operate during deformation. Liquid metals
are compelling materials for these applications because, in principle, they are
infinitely deformable while retaining metallic conductivity. Liquid metals have
been used for stretchable wires and interconnects, reconfigurable antennas, soft
sensors, self-healing circuits, and conformal electrodes. In contrast to Hg,
liquid metals based on gallium have low toxicity and essentially no vapor
pressure and are therefore considered safe to handle. Whereas most liquids bead
up to minimize surface energy, the presence of a surface oxide on these metals
makes it possible to pattern them into useful shapes using a variety of
techniques, including fluidic injection and 3D printing. In addition to forming
excellent conductors, these metals can be used actively to form memory devices,
sensors, and diodes that are completely built from soft materials. The properties
of these materials, their applications within soft and stretchable electronics,
and future opportunities and challenges are considered.
PMID- 28417535
TI - Rates of hypoglycaemia are lower in patients treated with insulin
degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of
the hypoglycaemia definition used.
AB - AIMS: To re-analyse, using a series of alternative hypoglycaemia definitions, the
data from 2 trials, DUAL I and V, in which the once-daily, fixed ratio
combination of insulin degludec/liraglutide (IDegLira) was compared with basal
insulin therapy. MATERIAL AND METHODS: Post hoc analyses of the DUAL I (patients
uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on
insulin glargine (IGlar) U100) trials were carried out using different
definitions of hypoglycaemia and according to whether treatments were
administered in the morning or afternoon. Rates of hypoglycaemia for the
definitions of confirmed and American Diabetes Association (ADA)-documented
symptomatic hypoglycaemia were compared according to age, gender and body mass
index (BMI). RESULTS: Although hypoglycaemia rates differed according to the
alternative hypoglycaemia definitions, rates were consistently lower with
IDegLira vs insulin degludec (IDeg) and IGlar U100. Despite glycated haemoglobin
concentrations being lower with IDegLira at end of treatment, confirmed and
nocturnal-confirmed hypoglycaemia rates were lower for IDegLira vs IDeg and IGlar
U100, irrespective of dosing time. The definitions of confirmed and ADA
documented symptomatic hypoglycaemia did not have a significant effect on the
treatment difference between IDegLira and IDeg, liraglutide or IGlar U100 when
further assessed by baseline age, gender and BMI. CONCLUSIONS: Treatment with
IDegLira, vs IDeg and IGlar U100, resulted in lower rates of hypoglycaemia
regardless of dosing time and definition of hypoglycaemia used. The choice of
hypoglycaemia definition did not influence the results of analyses when
stratified by age, sex and BMI.
PMID- 28417537
TI - The effects and mechanism of action of methane on ileal motor function.
AB - BACKGROUND: Methane has been associated with constipation-predominant irritable
bowel syndrome, slowing intestinal transit time by augmenting contractile
activity. However, the precise mechanism underlying this effect remains unclear.
Therefore, we investigated the mechanisms underlying the effect of methane on
contractile activity, and whether such effects are mediated by nerve impulses or
muscular contraction. METHODS: We connected guinea pig ileal muscle strips to a
force/tension transducer and measured amplitudes of contraction in response to
electrical field stimulation (EFS; 1, 2, 8, 16 Hz) following methane infusion in
the presence of tetradotoxin (TTX), atropine, guanethidine, or GR 113808. We then
performed calcium imaging using Oregon Green 488 BAPTA-1 AM in order to visualize
changes in calcium fluorescence in response to EFS following methane infusion in
the presence of TTX, atropine, or a high K+ solution. KEY RESULTS: Methane
significantly increased amplitudes of contraction (P<.05), while treatment with
TTX abolished such contraction. Methane-induced increases in amplitude were
inhibited when lower-frequency (1, 2 Hz) EFS was applied following atropine
infusion (P<.05). Neither guanethidine nor GR 113808 significantly altered
contraction amplitudes. Methane significantly increased calcium fluorescence,
while this increase was attenuated following atropine infusion (P<.05). Although
calcium fluorescence was increased by the high K+ solution under pretreatment
with TTX, the intensity of fluorescence remained unchanged after methane
infusion. CONCLUSIONS AND INFERENCES: The actions of methane on the intestine are
influenced by the cholinergic pathway of the enteric nervous system. Our findings
support the classification of methane as a gasotransmitter.
PMID- 28417538
TI - Synthesis of Long Oxahelicenes by Polycyclization in a Flow Reactor.
AB - A series of oxahelicenes composed of ortho/meta-annulated benzene/pyridine and 2H
pyran rings were synthesized on the basis of the cobalt(I)-mediated (or
rhodium(I)- or nickel(0)-mediated) double, triple, or quadruple [2+2+2]
cycloisomerization of branched aromatic hexa-, nona-, or dodecaynes, thus
allowing the construction of 6, 9, or 12 rings in a single operation. The use of
a flow reactor was found to be beneficial for the multicyclization reactions. The
stereogenic centers present in some of the oligoynes steered the helical folding
in such a way that the final oxa[9]-, [13]-, [17]- and [19]helicenes were
obtained in both enantiomerically and diastereomerically pure form. Specifically,
the oxa[19]helicenes beat the current record in the length of a helicene
backbone. Single-molecule conductivity was studied by the mechanically
controllable break-junction method with a pyridooxa[9]helicene.
PMID- 28417540
TI - Medium-chain triglycerides given in the early stage of mild-to-moderate
Alzheimer's disease enhance memory function.
PMID- 28417539
TI - USP22 mediates the multidrug resistance of hepatocellular carcinoma via the
SIRT1/AKT/MRP1 signaling pathway.
AB - Drug treatments for hepatocellular carcinoma (HCC) often fail because of
multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem
cells (CSCs), which are able to self-renew and differentiate, have recently been
shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22
(USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in
MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we
found that modified USP22 levels were responsible for the altered drug-resistant
phenotype of BEL7402 and BEL/FU cells. Downregulation of USP22 dramatically
inhibited the expression of ABCC1 (encoding MRP1) but weakly influenced ABCB1
(encoding P-glycoprotein). Sirtuin 1 (SIRT1) was reported previously as a
functional mediator of USP22 that could promote HCC cell proliferation and
enhance resistance to chemotherapy. In this study, USP22 directly interacted with
SIRT1 and positively regulated SIRT1 protein expression. Regulation of the
expression of both USP22 and SIRT1 markedly affected the AKT pathway and MRP1
expression. Inhibition of the AKT pathway by its specific inhibitor LY294002
resulted in downregulation of MRP1. USP22 and MRP1 expression was detected in 168
clinical HCC samples by immunohistochemical staining, and a firm relationship
between USP22 and MRP1 was identified. Together, these results indicate that
USP22 could promote the MDR in HCC cells by activating the SIRT1/AKT/MRP1
pathway. USP22 might be a potential target, through which the MDR of HCC in
clinical setting could be reversed.
PMID- 28417541
TI - Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal
cell carcinoma.
AB - Advanced-stage renal cell carcinoma (RCC) carries a dismal prognosis for
pediatric patients with few studied therapeutic options. Cabozantinib is a small
molecule tyrosine kinase inhibitor against the oncoprotein MET. It is currently
approved by the U.S. Food and Drug administration for second-line treatment of
RCC in adults. There is no published data on its use in children with RCC. We
report here two pediatric patients with recurrent metastatic RCC whose tumors
expressed MET and were treated with cabozantinib. Both patients had significant
disease regression and symptomatic improvement for over 15 months with tolerable
adverse effects. Cabozantinib can maintain prolonged disease control in pediatric
RCC and warrants further study.
PMID- 28417542
TI - Vertically Oriented Graphene Nanoribbon Fibers for High-Volumetric Energy Density
All-Solid-State Asymmetric Supercapacitors.
AB - Graphene fiber based micro-supercapacitors (GF micro-SCs) have attracted great
attention for their potential applications in portable and wearable electronics.
However, due to strong pi-pi stacking of nanosheets for graphene fibers, the
limited ion accessible surface area and slow ion diffusion rate leads to low
specific capacitance and poor rate performance. Here, the authors report a
strategy for the synthesis of a vertically oriented graphene nanoribbon fiber
with highly exposed surface area through confined-hydrothermal treatment of
interconnected graphene oxide nanoribbons and consequent laser irradiation
process. As a result, the as-obtained fiber shows high length specific
capacitance of 3.2 mF cm-1 and volumetric capacitance of 234.8 F cm-3 at 2 mV s-1
, as well as excellent rate capability and outstanding cycling performance (96%
capacitance retention after 10 000 cycles). Moreover, an all-solid-state
asymmetric supercapacitor based on graphene nanoribbon fiber as negative
electrode and MnO2 coated graphene ribbon fiber as positive electrode, shows high
volumetric capacitance and energy density of 12.8 F cm-3 and 5.7 mWh cm-3
(normalized to the device volume), respectively, much higher than those of
previously reported GF micro-SCs, as well as a long cycle life with 88% of
capacitance retention after 10 000 cycles.
PMID- 28417543
TI - Efficiency of Cathodoluminescence Emission by Nitrogen-Vacancy Color Centers in
Nanodiamonds.
AB - Correlated electron microscopy and cathodoluminescence (CL) imaging using
functionalized nanoparticles is a promising nanoscale probe of biological
structure and function. Nanodiamonds (NDs) that contain CL-emitting color centers
are particularly well suited for such applications. The intensity of CL emission
from NDs is determined by a combination of factors, including particle size,
density of color centers, efficiency of energy deposition by electrons passing
through the particle, and conversion efficiency from deposited energy to CL
emission. This paper reports experiments and numerical simulations that
investigate the relative importance of each of these factors in determining CL
emission intensity from NDs containing nitrogen-vacancy (NV) color centers. In
particular, it is found that CL can be detected from NV-doped NDs with dimensions
as small as ~40 nm, although CL emission decreases significantly for smaller NDs.
PMID- 28417544
TI - Urine biomarkers of acute kidney injury in noncritically ill, hospitalized
children treated with chemotherapy.
AB - BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common
nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early
acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center
(Canada, United States) pilot study to prospectively measure serum creatinine
(SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin
18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and
in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney
Disease Improving Global Outcomes (KDIGO) definition. We compared
postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3
days later) to pre-infusion concentrations. We calculated area under the receiver
operating characteristic curve (AUC) for postinfusion biomarkers to discriminate
for AKI. RESULTS: Prechemotherapy infusion NGAL and IL-18 concentrations were not
higher than nonchemotherapy control concentrations. Increasing chemotherapy dose
was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P <
0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were
significantly higher than pre-infusion biomarker concentrations (P < 0.05),
during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb
infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured
immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard
error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were
not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all
biomarker AUCs (Cis-Carb and Ifos) improved. CONCLUSION: Urine NGAL and IL-18
show promise as early AKI diagnostic tests in children treated with ifosfamide
and may have a potential role in drug toxicity monitoring.
PMID- 28417545
TI - Gender composition of the occupation, sexual orientation, and mental health in
young adulthood.
AB - The gender composition of the occupation has important implications for work
conditions, rewards, and experiences, but little is known about whether it
impacts workers' mental health. The present study seeks to answer this question
by focusing on depressive symptoms and drug dependence symptoms as mental health
outcomes and young adulthood as the life course context. The study further
examines whether the association varies by sexual orientation, considering that
occupational gender composition affects levels of stress exposure and social
support availability in different ways for heterosexuals and sexual minorities.
The analysis of the U.S. data, the National Longitudinal Study of Adolescent to
Adult Health (Add Health), shows that among heterosexuals, working in a more
female-typical occupation is associated with lower levels of drug dependence
symptoms for women and higher levels of depressive symptoms for men. Sexual
minorities show a diverging pattern-working in a more female-typical occupation
is associated with worse mental health for sexual minority women and better
mental health for sexual minority men.
PMID- 28417546
TI - Novel Structure for High Performance UV Photodetector Based on BiOCl/ZnO Hybrid
Film.
AB - A novel type of high performance ultraviolet (UV) photodetector (PD) based on a
ZnO film has been prepared by incorporating a BiOCl nanostructure into the film.
The responsivity of the BiOCl/ZnO hybrid film PD in UV region can reach 182.87 mA
W-1 , which is about 2.72 and 6.87 times for that of TiO2 /ZnO hybrid film PD and
pure ZnO film PD. The rise/decay time of BiOCl/ZnO hybrid film PD is 25.83/11.25
s, which is much shorter than that of TiO2 /ZnO hybrid film PD (51.94/26.05 s)
and pure ZnO film PD (69.34/>120 s). The BiOCl nanostructure can inject
photogenerated electrons into the ZnO film under UV light illumination, leading
to the increase of photocurrent, and forms barriers to block the straight
transmission of electrons between electrodes, resulting in the decrease of decay
time. The results of control experiment show that the transfer path of
photogenerated electrons formed by p-n junction will be cut off after depositing
gold nanoparticles on the film surface, which means this hybrid film is a unique
and novel structure to improve the optoelectronic performance of photodetectors.
This novel BiOCl/ZnO hybrid structure paves new route for the development of film
PDs based on ZnO film.
PMID- 28417547
TI - A long-term follow-up study of subtotal splenectomy in children with hereditary
spherocytosis.
AB - BACKGROUND: Hereditary spherocytosis (HS) is a heterogeneous hemolytic anemia
treated with splenectomy in patients suffering from severe or moderate disease.
Total splenectomy, however, renders patients vulnerable to overwhelming
postsplenectomy infection despite preventive measures. Although subtotal
splenectomy has been advocated as an alternative to total splenectomy, long-term
follow-up data are scarce. We investigated how often hematologic recurrences
requiring secondary total splenectomy occurred. PROCEDURE: With a follow-up of at
least 5 years, we analyzed the data of 12 patients, aged 11 years maximum (median
6.5 years), who had undergone intended subtotal splenectomy, and 9 patients
(median age 11.9 years), who had undergone total splenectomy. We compared their
hematologic results and searched for factors associated with secondary spleen
surgery. RESULTS: Hemolysis was reduced after subtotal splenectomy and absent
after total splenectomy. Subtotal splenectomy was not successful in three
children because no functional splenic remnant remained after 6 months (one
conversion at surgery; one necrosis of splenic remnant; one early secondary
splenectomy). Four children required secondary splenectomy after a median of 5
years for hematologic recurrence. In the remaining five patients, a functional
splenic remnant was present for at least 5.5 years. The median time to secondary
total splenectomy after intended subtotal splenectomy was 5.2 years. In all
patients requiring secondary total splenectomy, increased reticulocyte levels
within 2 years indicated hematologic recurrence. CONCLUSIONS: Subtotal
splenectomy can be an alternative for total splenectomy in young patients with
HS. It allows for hematologic improvement and may preserve splenic immune
function for as many as 5 years.
PMID- 28417548
TI - Resistive Switching Performance Improvement via Modulating Nanoscale Conductive
Filament, Involving the Application of Two-Dimensional Layered Materials.
AB - Reversible chemical and structural changes induced by ionic motion and reaction
in response to electrical stimuli leads to resistive switching effects in metal
insulator-metal structures. Filamentary switching based on the formation and
rupture of nanoscale conductive filament has been applied in non-volatile memory
and volatile selector devices with low power consumption and fast switching
speeds. Before the mass production of resistive switching devices, great efforts
are still required to enable stable and reliable switching performances. The
conductive filament, a bridge of microscopic metal-insulator-metal structure and
macroscopic resistance states, plays an irreplaceable part in resistive switching
behavior, as unreliable performance often originates from unstable filament
behavior. In this Review, departing from the filamentary switching mechanism and
the existing issues, recent advances of the switching performance improvement
through the conductive filament modulation are discussed, in the sequence of
material modulation, device structure design and switching operation scheme
optimization. In particular, two-dimensional (2D) nanomaterials with excellent
properties including and beyond graphene, are discussed with emphasis on
performance improvement by their active roles as the switching layer, insertion
layer, thin electrode, patterned electrode, and edge electrode, etc.
PMID- 28417549
TI - Searching for a job: Cardiac responses to acute stress and the mediating role of
threat appraisal in young people.
AB - Being unemployed and looking for a job has become a source of stress for many
people in several European countries. However, little attention has been paid to
the impact of this stressful situation on the individuals' psychophysiological
stress responses. The aim of this study was to investigate the effect of being an
unemployed job seeker on cognitive threat appraisal and cardiac responses to a
psychosocial stressor. We exposed a group of unemployed job seekers (N = 42) and
a matched group of unemployed non-job seekers (N = 40) to a standardized social
stressor in form of job interview, the Trier Social Stress Test. Our results
showed that unemployed job seekers manifest lower cardiac responses, along with a
lower cognitive threat appraisal, compared to non-job seekers. Moreover, we
observed a full mediating role of cognitive threat appraisal on the relationship
between being an unemployed job seeker and cardiac responses to stress. These
findings reveal that being unemployed and looking for a job has an effect on
physiological responses to acute stress, as well as the importance of
psychological process related to the situation. These responses might lead to
negative health and motivational consequences. Theoretical and practical
implications are discussed.
PMID- 28417550
TI - Burden, emotional distress and quality of life among informal caregivers of lung
cancer patients: An exploratory study.
AB - This study was conducted to explore the interrelationships among caregiver
burden, emotional status and quality of life (QoL) in caregivers of lung cancer
patients, and to identify whether caregiver burden and health status are
associated with patient emotional status and QoL. Forty-three dyads of lung
cancer patients and their caregivers were included for analysis. Caregiver
reported outcomes were measured by Caregiver Burden Scale (CBS), Caregivers
Quality of Life Index-Cancer (CQOLC) and Hospital Anxiety and Depression Scale
(HADS), while patient-reported outcomes were collected by HADS and Lung Cancer
Symptom Scale (LCSS). The majority of the CBS and CQOLC scores were significantly
higher in anxious and depressed caregivers than non-anxious and non-depressed
caregivers (p < .01 or .05). Caregivers of depressed patients experienced
significantly greater emotional distress than those of non-depressed patients (p
< .01). Significantly positive associations were identified among most of the
CBS, CQOLC and caregiver HADS scores. Patient LCSS scores were positively
correlated with the CBS and caregiver HADS scores, and patient HADS scores were
also positively related to caregiver HADS scores. The close interrelationships
between caregiver and patient health outcomes provide evidence that lung cancer
patients and their caregivers should be viewed as a unit in future supportive
service models.
PMID- 28417551
TI - Morbidity and mortality after treatment of Ewing sarcoma: A single-institution
experience.
AB - BACKGROUND: Children, adolescents, and young adults treated for Ewing sarcoma
(ES) are at risk for disease-related and treatment-related complications. We
aimed to describe early and late overall mortality, cause-specific mortality, and
key adverse health outcomes in a large, single-institutional cohort of patients
with ES. METHODS: Patients with ES diagnosed at age less than 40 years and
treated at Memorial Sloan Kettering between 1974 and 2012 were included. Overall
survival was estimated using Kaplan-Meier methods. Cox proportional hazards were
used to examine the association of clinical and pathologic variables with overall
survival. Cause-specific mortality was evaluated with the cumulative incidence
function accounting for competing risks. RESULTS: Three hundred patients with ES
(60.3% male; median age at diagnosis: 16.8 years [range: 0.3-39]; 30.0% with
metastatic disease at diagnosis) were followed for a median of 7.8 years (range:
0.2-37). Five-year overall survival was 65.2% (95% confidence interval [95% CI],
59.8-71.1%) for the entire cohort; 78.6% for those with localized disease; 40.1%
for those with isolated pulmonary metastases; and 28.1% for those with
extrapulmonary metastases. In multivariable analysis, older age at diagnosis,
minority race/ethnicity, and metastatic disease at diagnosis were associated with
inferior survival. Ten-year cumulative incidence of relapse/progression was
40.1%, with eight late relapses occurring at a median of 6.3 years after
diagnosis (range: 5-14). Seventeen patients developed subsequent neoplasms
(treatment-related myelodysplastic syndrome/acute myelogenous leukemia = 9; solid
tumors = 6; nonmelanoma skin cancer [NMSC] = 4). Excluding NMSC and melanoma in
situ, the cumulative incidence of subsequent malignant neoplasms at 25 years was
15% (95% CI, 4.8-25.1%). CONCLUSION: Patients with ES are at high risk for
relapse/progression and second cancers.
PMID- 28417552
TI - Enhanced phototoxicity of photodynamic treatment by Cx26-composed GJIC via ROS-,
calcium- and lipid peroxide-mediated pathways.
AB - In spite of the promising initial treatment responses presented by photodynamic
therapy (PDT), 5-year recurrence rates remain high level. Therefore, improvement
in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26
composed gap junctional intercellular communication (GJIC) enhances the
intercellular propagation of "death signal", thereby increasing chemotherapeutic
cytotoxicity. However, it is unclear whether Cx26-formed GJIC has an effect on
PDT phototoxicity. The results in the present study showed that Cx26-composed GJ
formation at high density enhances the phototoxicity of Photofrin-PDT. When the
Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high
density cultures substantially reduces, indicating that the enhanced PDT
phototoxicity at high density is mediated by Cx26-composed GJIC. The GJIC
mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid
peroxide-mediated stress signaling pathways. The work presents the ability of
Cx26-composed GJIC to enhance the sensitivity of malignant cells to PDT, and
indicates that maintenance or increase of Cx26-formed GJIC may be a profitable
strategy towards the enhancement of PDT therapeutic efficiency. Picture: The
survival response of Photofrin-PDT in Dox-treated (Cx26 expressing, GJ-formed)
and Dox-untreated cells (Cx26 non-expressing, GJ-unformed) at high-cell density
condition.
PMID- 28417553
TI - Calcineurin inhibitor-free strategies for prophylaxis and treatment of GVHD in
children with posterior reversible encephalopathy syndrome after stem cell
transplantation.
AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a distinct
clinico-radiologic entity that can occur following allogeneic hematopoietic stem
cell transplantation, often in the context of treatment with calcineurin
inhibitors (CNIs). PROCEDURE: We describe the results of CNI-free management of
14 children with PRES and review the clinical and radiologic manifestations of
their presentation. RESULTS: Discontinuation of CNIs usually resulted in
remission of PRES, but patients with established graft versus host disease (GVHD)
at the time when treatment was changed often experienced progressive GVHD despite
administration of immune suppressive and modulating treatments. All but three
patients experienced full neurologic recovery. Nine children died as a result of
either GVHD, disease relapse, or severe infection. CONCLUSIONS: Discontinuation
of CNIs results in neurologic improvement in most cases, but superior alternative
immune modulatory treatment is needed to prevent progression of established GVHD.
PMID- 28417555
TI - A Novel Bat-Shaped Dicyanomethylene-4H-pyran-Functionalized Naphthalimide for
Highly Efficient Solution-Processed Multilevel Memory Devices.
AB - Small-molecule-based multilevel memory devices have attracted increasing
attention because of their advantages, such as super-high storage density, fast
reading speed, light weight, low energy consumption, and shock resistance.
However, the fabrication of small-molecule-based devices always requires
expensive vacuum-deposition techniques or high temperatures for spin-coating.
Herein, through rational tailoring of a previous molecule, DPCNCANA (4,4'-(6,6'
bis(2-octyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)-9H,9'H-[3,3'
bicarbazole]-9,9'-diyl)dibenzonitrile), a novel bat-shaped A-D-A-type (A-D
A=acceptor-donor-acceptor) symmetric framework has been successfully synthesized
and can be dissolved in common solvents at room temperature. Additionally, it has
a low-energy bandgap and dense intramolecular stacking in the film state. The
solution-processed memory devices exhibited high-performance nonvolatile
multilevel data-storage properties with low switching threshold voltages of about
-1.3 and -2.7 V, which is beneficial for low power consumption. Our result should
prompt the study of highly efficient solution-processed multilevel memory devices
in the field of organic electronics.
PMID- 28417556
TI - An HLA-B7-specific antibody in an HLA-B*07 positive patient explained by a
nonexpressed allele (HLA-B*07:181N).
AB - Antibody identification by a bead array assay in a kidney patient revealed
several HLA-specific antibodies including one directed against the HLA-B7
antigen. Low-resolution typing of the patient indicated the presence of an HLA
B*07 allele. To rule out an HLA-specific autoantibody the HLA-typing of the
patient was further refined by nucleotide sequencing on a next-generation
sequencing platform and eventually showed an HLA-B*39:01:01:03 and HLA-B*07:181N
genotype. Thereby the allospecific nature of the antibody was proven. The HLA-B7
specific antibody could be explained by an immunization during the first kidney
transplantation in 1996 with an HLA-B*07 positive donor. When assessing the
plausibility of antibodies, the presence of nonexpressed alleles should be taken
into consideration.
PMID- 28417558
TI - The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related
traits and mediates by interacting with Apo-A1.
AB - OBJECTIVE: Despite alarming obesity levels in the Arabian Peninsula, its
population lacks convincingly identified genetic determinants of obesity. A
genome-wide association study was performed for obesity-related anthropometric
traits in Arabs and to decipher mechanisms by which the variants mediate traits.
METHODS: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab
individuals (largely with Class I obesity) from Kuwait. Genome-wide association
tests for obesity-related anthropometric traits were performed. Top associations
were tested for replication in an independent cohort (1,176 unrelated Arabs).
Resultant variants were investigated for interactions with obesity-related plasma
biomarkers. Pathway analysis was performed on genes harboring markers in linkage
disequilibrium (LD) with identified variants. RESULTS: The
rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist
circumference (WC) at nearly genome-wide significance (P = 8.92E-08). WC was
inversely related with Apo-A1 or high-density lipoprotein levels; individuals
with the AG genotype exhibited stronger relationship than those with the
reference AA genotype. Interaction involving the AG genotype (effect allele = G)
significantly contributed to an increase in anthropometric traits (particularly
WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped
onto an interaction network (with TP53 as central element) of established
obesity/diabetes-related protein components. CONCLUSIONS: The TCN2 variant acts
as a risk factor for WC in the Arab population. The variant mediates obesity
related anthropometric traits via interactions with Apo-A1/high-density
lipoprotein or TP53.
PMID- 28417557
TI - A Multitarget Approach toward the Development of 8-Substituted Purines for
Photoprotection and Prevention of UV-Related Damage.
AB - Ultraviolet (UV) light is the most abundant and significant modifiable risk
factor for skin cancer and many other skin diseases such as early photo-aging.
Across the solar radiation spectrum, UV light is the main cause behind skin
problems. In the search for novel photoprotective compounds, a new series of 8
substituted purines were synthesized from commercially available 6-hydroxy-4,5
diaminopyrimidine hemisulfate or 4,5-diaminopyrimidine. All title compounds were
investigated for their UV filtering, antioxidant, antifungal, and
antiproliferative activities. For the photoprotection assays we used a diffuse
transmittance technique to determine the sun protection factor (SPF) in vitro,
and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant
power (FRAP) tests for evaluating the antioxidant activity of the more potent
compounds. Among them, 8-(2,5-dihydroxyphenyl)-7H-purin-6-ol (compound 26) proved
to be a good radical scavenger and is also endowed with broad-spectrum UVA
filtering capabilities, suitable for further development as a protective
molecule.
PMID- 28417559
TI - Asenapine modulates mood-related behaviors and 5-HT1A/7 receptors-mediated
neurotransmission.
AB - AIM: Asenapine is a new atypical antipsychotic prescribed for the treatment of
psychosis/bipolar disorders that presents higher affinity for serotonergic than
dopaminergic receptors. The objective of this study was to investigate its
antidepressant-like and antimanic-like properties on relevant animal models of
depression and mania and to assess the acute and chronic effect of Asenapine on
dorsal raphe nucleus (DRN) 5-HT cell firing activity. METHODS: We assessed the
effects of Asenapine using in vivo electrophysiological and behavioral assays in
rats. RESULTS: Behavioral experiments showed that Asenapine had no significant
effect on immobility time in the forced swim test (FST) in control rats. In the
ACTH-treated rats, a model of antidepressant-resistance, Asenapine failed to
alter immobility time in the FST. In contrast in the sleep deprivation (SD) model
of mania, acute administration of Asenapine significantly decreased the
hyperlocomotion of SD rats. In the DRN, acute administration of Asenapine reduced
the suppressant effect of the selective 5-HT7 receptor agonist LP-44 and of the
prototypical 5-HT1A receptor agonist 8-OH-DPAT on 5-HT neuronal firing activity.
In addition, chronic treatment with Asenapine enhanced DRN 5-HT neuronal firing
and this effect was associated with an alteration of the 5-HT7 receptor
responsiveness. CONCLUSION: These results confirm that Asenapine displays robust
antimanic property and effective in vivo antagonistic activity at 5-HT1A/7
receptors.
PMID- 28417560
TI - Treatment of tumor in lymph nodes using near-infrared laser light-activated
thermosensitive liposome-encapsulated doxorubicin and gold nanorods.
AB - Tumor metastasis to lymph nodes is an important contributory factor for cancer
related deaths despite recent developments in cancer therapy. In this study, we
demonstrate that tumor in the proper axillary lymph node (PALN) of the mouse can
be treated by the application of external laser light to trigger the unloading of
doxorubicin (DOX) encapsulated in thermosensitive liposomes (TSLs) administered
together with gold nanorods (GNRs). GNRs + DOX-TSLs were injected into a mouse
lymph node containing cancer cells (malignant fibrous histiocytoma-like cells)
and intranodal DOX release was activated using near-infrared (NIR) laser
irradiation. The temperature changes arising from the laser-irradiated GNRs
triggered the release of DOX from the TSLs. A greater degree of inhibition of
tumor growth was found in the co-therapy group compared to the other groups. The
treatment effect was achieved by a combination of chemotherapy and NIR-activated
hyperthermia. In vivo bioluminescence imaging and histological analysis confirmed
tumor necrosis in response to combined treatment. This work presents a
theranostic approach with excellent treatment results that has the potential to
be developed into an alternative to surgery for the treatment of breast cancer
metastasis.
PMID- 28417561
TI - Population Pharmacokinetics of Morphine in Patients With Nonalcoholic
Steatohepatitis (NASH) and Healthy Adults.
AB - Altered expression and function of transporters in nonalcoholic steatohepatitis
(NASH) patients may affect the pharmacokinetics (PK), efficacy, and safety of
substrate drugs. A population pharmacokinetic (PopPK) analysis was performed to
assess differences in morphine and morphine-3-glucuronide (M3G) disposition in
NASH and healthy subjects. A total of 315 serum and 42 urine samples from 21
subjects (14 healthy; 7 NASH) were analyzed using NONMEM. Morphine and M3G PK
were described by three- and one-compartment models, respectively. After
accounting for the effect of total body weight on all clearance and volume of
distribution parameters using an allometric scaling approach, NASH severity score
(NASF; combination of fibrosis and nonalcoholic fatty liver disease activity
scores) was the most significant predictor of differences in M3G exposure. The
model predicted a linear decrease in the clearance of M3G with increasing NASF
scores on a natural logarithmic scale. These results may provide some insight
into the potential effect of NASH on the disposition of hepatic transporter
substrates.
PMID- 28417563
TI - Nutritional parameters as mortality predictors in haemodialysis: Differences
between genders.
AB - BACKGROUND: Malnutrition is common in patients undergoing haemodialysis (HD).
Several studies have described different nutritional parameters as mortality
predictors but few have studied whether there are differences between genders.
This study aimed to evaluate which nutrition parameters may be associated with
mortality in patients undergoing long-term HD depending on their gender. METHODS:
Longitudinal prospective multicentre study with 12 months of follow-up.
Anthropometric and laboratory measures were obtained from 697 patients. RESULTS:
Men who died were older, had lower dry weight, body mass index, potassium,
phosphorus and albumin, compared with male patients who survived. Female patients
who died had lower albumin and nPCR compared with survivors. Kaplan-Meier
analysis displayed a significantly worse survival in patients with albumin <3.5
g/dl in both genders and with body mass index <23 kg/m2 in men. In the Cox
regression analysis patients overall mortality was related to body mass index <23
kg/m2 , potassium <=5.5 mEq/l and phosphorus <3.0 mg/dl for male patients and
albumin <3.5 g/dl and normalised protein catabolic rate (nPCR) <0.8 g/kg/day for
both genders. Associations between albumin, body mass index and mortality risk
continued to be significant after adjustments for age, length of time on dialysis
and diabetes for males. However, in women, only albumin persisted as an
independent predictor of death. CONCLUSION: Depending on the gender, different
parameters such as protein intake, potassium, phosphorus, body mass index and
albumin are associated with mortality in patients undergoing HD. Albumin <3.5
g/dl is an independent mortality predictor in both genders, whereas a body mass
index <23 kg/m2 is an independent predictor of death, but only in men.
PMID- 28417562
TI - Climate variability drives recent tree mortality in Europe.
AB - Tree mortality is an important process in forest ecosystems, frequently
hypothesized to be highly climate sensitive. Yet, tree death remains one of the
least understood processes of forest dynamics. Recently, changes in tree
mortality have been observed in forests around the globe, which could profoundly
affect ecosystem functioning and services provisioning to society. We describe
continental-scale patterns of recent tree mortality from the only consistent pan
European forest monitoring network, identifying recent mortality hotspots in
southern and northern Europe. Analyzing 925,462 annual observations of 235,895
trees between 2000 and 2012, we determine the influence of climate variability
and tree age on interannual variation in tree mortality using Cox proportional
hazard models. Warm summers as well as high seasonal variability in precipitation
increased the likelihood of tree death. However, our data also suggest that
reduced cold-induced mortality could compensate increased mortality related to
peak temperatures in a warming climate. Besides climate variability, age was an
important driver of tree mortality, with individual mortality probability
decreasing with age over the first century of a trees life. A considerable
portion of the observed variation in tree mortality could be explained by
satellite-derived net primary productivity, suggesting that widely available
remote sensing products can be used as an early warning indicator of widespread
tree mortality. Our findings advance the understanding of patterns of large-scale
tree mortality by demonstrating the influence of seasonal and diurnal climate
variation, and highlight the potential of state-of-the-art remote sensing to
anticipate an increased likelihood of tree mortality in space and time.
PMID- 28417564
TI - 3D in vivo imaging with extended-focus optical coherence microscopy.
AB - Optical coherence microscopy (OCM) has unique advantages of non-invasive 3D
imaging without the need of exogenous labels for studying biological samples.
However, the imaging depth of this technique is limited by the tradeoff between
the depth of focus (DOF) and high lateral resolution in Gaussian optics. To
overcome this limitation, we have developed an extended-focus OCM (xf-OCM)
imaging system using quasi-Bessel beam illumination to extend the DOF to ~100
MUm, about 3-fold greater than standard OCM. High lateral resolution of 1.6 MUm
ensured detailed identification of structures within live animal samples. The
insensitivity to spherical aberrations strengthened the capability of our xf-OCM
system in 3D biological imaging.
PMID- 28417565
TI - Treatment of advanced melanoma with laser immunotherapy and ipilimumab.
AB - Immunotherapy has become a promising modality for melanoma, especially using
checkpoint inhibitors, which revive suppressed T cells against the cancer. Such
inhibitors should work better when combined with other treatments which could
increase the number and quality of anti-tumor T cells. We treated one patient
with advanced (stage IV) melanoma, using the combination of laser immunotherapy
(LIT), a novel immunological approach for metastatic cancers that has been shown
to stimulate adaptive immunity, and ipilimumab. The patient was treated with LIT,
followed with one course of ipilimumab 3 months after the beginning of LIT. After
LIT treatment, all treated cutaneous melanoma in head and neck cleared
completely. After the application of ipilimumab, all the tumor nodules in the
lungs decreased. The patient had remained tumor free for one year. While
anecdotal, the responses seen in this patient support the hypothesis that laser
immunotherapy increases the number and quality of anti-tumor T cells so that
ipilimumab and other checkpoint inhibitors are more effective in enhancing the
therapeutic effects. Picture: Schematic of treatment using laser immunotherapy
and ipilimumab on a stage IV melanoma patient.
PMID- 28417566
TI - Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for
Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.
AB - Cannabis sativa withdrawal syndrome is characterized mainly by psychological
symptoms. By using computational tools, the aim of this study was to propose drug
candidates for treating withdrawal syndrome based on the natural ligands of the
cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n
pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive
predictions as a human CB1 ligand and for facile synthetic accessibility.
Therefore, ZINC1730183 is a favorable candidate scaffold for further research
into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome.
PMID- 28417567
TI - A Versatile and Simple Approach to Generate Light Emission in Semiconductors
Mediated by Electric Double Layers.
AB - The light-emitting device is the primary device for current light sources. In
principle, conventional light-emitting devices need heterostructures and/or
intentional carrier doping to form a p-n junction. This junction formation is,
however, very difficult to achieve for most emerging semiconductors, and the
fabrication of light-emitting devices is invariably a significant challenge. This
study proposes a versatile and simple approach to realize light-emitting devices.
This proposed device requires only a semiconducting film with two electrodes that
are covered with an electrolyte. This unique structure achieves light emission at
a voltage slightly larger than the bandgap energy of materials. This study
applies this concept to emerging direct bandgap semiconductors, such as
transition metal dichalcogenide monolayers and zinc oxide single crystals. These
devices generate obvious light emission and provide sufficient evidence of the
formation of a dynamic p-i-n junction or tunneling junction, presenting a
versatile technique to develop optoelectronic devices.
PMID- 28417569
TI - Lessons from a violent death: The heart & soul of change.
PMID- 28417570
TI - Championing the National Strategic Framework for Rural and Remote Health.
PMID- 28417568
TI - Cisplatin-resistant cancer cells are sensitive to Aurora kinase A inhibition by
alisertib.
AB - De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a
clinical challenge in gastric cancer treatment. Aberrant expression and
activation of aurora kinase A (AURKA) and eukaryotic translation initiation
factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated
the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis
demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and
de novo CDDP-resistant gastric cancer models. Inhibition of AURKA with MLN8237
(alisertib) alone or in combination with CDDP significantly suppressed viability
of CDDP-resistant cancer cells (P < 0.01). Additionally, inhibition or knockdown
of AURKA decreased protein expression of p-eIF4E (S209), HDM2, and c-MYC in CDDP
resistant cell models. This was associated with a significant decrease in cap
dependent translation levels (P < 0.01). In vivo tumor xenografts data
corroborated these results and confirmed that inhibition of AURKA was sufficient
to overcome CDDP resistance in gastric cancer. Our data demonstrate that AURKA
promotes acquired and de novo resistance to CDDP through regulation of p-eIF4E
(S209), c-MYC, HDM2, and cap-dependent translation. Targeting AURKA could be an
effective therapeutic approach to overcome CDDP resistance in refractory gastric
cancer and possibly other cancer types.
PMID- 28417571
TI - A health commission for regional, rural and remote Australia.
PMID- 28417572
TI - John Humphreys.
PMID- 28417573
TI - Spotlights on our sister journals: Angew. Chem. Int. Ed. 18/2017.
PMID- 28417574
TI - Light-Emitting Diode treatment ameliorates allergic lung inflammation in
experimental model of asthma induced by ovalbumin.
AB - Since asthma is a multifactorial disease where treatment sometimes is not
effective, new therapies that improve the respiratory discomfort of patients are
of great importance. Phototherapy as Light-emitting diode (LED) has emerged as a
treatment that presents good results for diseases that are characterized by
inflammation. Thus, our objective was to investigate the effects of LED on lung
inflammation, by an evaluation of lung cell infiltration, mucus secretion,
oedema, and the production of cytokines. Male Balb/c mice were or not sensitized
and challenged with ovalbumin (OVA) and treated or not with LED therapy (1 h and
4 h after each OVA challenge). Twenty-four hours after the last OVA challenge,
analyzes were performed. Our results showed that LED treatment in asthmatic mice
reduced the lung cell infiltration, the mucus production, the oedema, and the
tracheal's contractile response. It also increased the IL-10 and the IFN-gamma
levels. The effects of LED treatment on lung inflammation may be modulated by IL
10, IFN-gamma, and by mast cells. This study may provide important information
about the effects of LED, and in addition, it may open the possibility of a new
approach for the treatment of asthma.
PMID- 28417575
TI - Effect of weight reduction on glycated haemoglobin in weight loss trials in
patients with type 2 diabetes.
AB - AIM: To quantify the effect of weight loss on glycated haemoglobin (HbA1c) at
group level, based on data from published weight loss trials in overweight and
obese patients with type 2 diabetes (T2D). METHODS: A systematic literature
search in MEDLINE, EMBASE and Cochrane CENTRAL (January 1990 through December
2012) was conducted to identify prospective trials of energy-reduced diets,
obesity drugs or bariatric surgery in adult, overweight and obese patients with
T2D. Based on clinical data with follow-up from 3 to 24 months, a linear model
was developed to describe the effect of weight reduction on HbA1c. RESULTS: The
literature search identified 58 eligible articles consisting of 124 treatment
groups and 17 204 subjects, yielding a total of 250 data points with concurrent
mean changes from baseline in weight and HbA1c. The model-based analyses
indicated a linear relationship between weight loss and HbA1c reduction, with an
estimated mean HbA1c reduction of 0.1 percentage points for each 1 kg of reduced
body weight for the overall population. Baseline HbA1c was a significant
covariate for the relationship between weight loss and HbA1c: high HbA1c at
baseline was associated with a greater reduction in HbA1c for the same degree of
weight loss. The collected trial data also indicated weight-loss-dependent
reductions in antidiabetic medication. CONCLUSIONS: At group level, weight loss
in obese and overweight patients with T2D was consistently accompanied by HbA1c
reduction in a dose-dependent manner. The model developed in the present study
estimates that for each kg of mean weight loss, there is a mean HbA1c reduction
of 0.1 percentage points. HbA1c-lowering is greater in populations with poor
glycaemic control than in well controlled populations with the same degree of
weight loss. This summary of data from previous trials regarding the effect of
weight reduction on HbA1c may be used to support the design and interpretation of
future studies that aim to demonstrate the efficacy of weight loss interventions
for T2D treatment.
PMID- 28417576
TI - The Relation between Chemical Bonding and Ultrafast Crystal Growth.
AB - Glasses are often described as supercooled liquids, whose structures are
topologically disordered like a liquid, but nevertheless retain short-range
structural order. Structural complexity is often associated with complicated
electron-charge distributions in glassy systems, making a detailed investigation
challenging even for short-range structural order, let alone their atomic
dynamics. This is particularly problematic for lone-pair-rich, semiconducting
materials, such as phase-change materials (PCMs). Here, this study shows that
analytical methods for studying bonding, based on the electron-charge density,
rather than a conventional atomic pair-correlation-function approach, allows an
in-depth investigation into the chemical-bonding network, as well as lone pairs,
of the prototypical PCM, Ge2 Sb2 Te5 (GST). It is demonstrated that the
structurally flexible building units of the amorphous GST network, intimately
linked to the presence of distinctly coexisting weak covalent and lone-pair
interactions, give rise to cooperative structural-ordering processes, by which
ultrafast crystal growth becomes possible. This finding may universally apply to
other PCMs.
PMID- 28417577
TI - Metal Hydride Nanoparticles with Ultrahigh Structural Stability and Hydrogen
Storage Activity Derived from Microencapsulated Nanoconfinement.
AB - Metal hydrides (MHs) have recently been designed for hydrogen sensors, switchable
mirrors, rechargeable batteries, and other energy-storage and conversion-related
applications. The demands of MHs, particular fast hydrogen absorption/desorption
kinetics, have brought their sizes to nanoscale. However, the nanostructured MHs
generally suffer from surface passivation and low aggregation-resisting
structural stability upon absorption/desorption. This study reports a novel
strategy named microencapsulated nanoconfinement to realize local synthesis of
nano-MHs, which possess ultrahigh structural stability and superior desorption
kinetics. Monodispersed Mg2 NiH4 single crystal nanoparticles (NPs) are in situ
encapsulated on the surface of graphene sheets (GS) through facile gas-solid
reactions. This well-defined MgO coating layer with a thickness of ~3 nm
efficiently separates the NPs from each other to prevent aggregation during
hydrogen absorption/desorption cycles, leading to excellent thermal and
mechanical stability. More interestingly, the MgO layer shows superior gas
selective permeability to prevent further oxidation of Mg2 NiH4 meanwhile
accessible for hydrogen absorption/desorption. As a result, an extremely low
activation energy (31.2 kJ mol-1 ) for the dehydrogenation reaction is achieved.
This study provides alternative insights into designing nanosized MHs with both
excellent hydrogen storage activity and thermal/mechanical stability exempting
surface modification by agents.
PMID- 28417579
TI - Sleep disorders require a comprehensive evaluation and confirmation with
polysomnography in patients with multiple sclerosis.
PMID- 28417580
TI - Response to Xia et al.
PMID- 28417581
TI - Radiopacity of Resin Cements Using Digital Radiography.
AB - STATEMENT OF PROBLEM: Monitoring performance of glass-ceramic based indirect
restorations using radiographic imaging might be difficult due to their low
radiopacity. Therefore, materials used for their cementation must possess
adequate radiopacity. PURPOSE: This study determined radiopacity of a group of
resin-cements used for adhesive-cementation of glass-ceramic-based restorations
using digital radiography. METHODS: Two specimens were prepared from a group of
resin cements (VariolinkII-opaque, VariolinkII-opaque (base), VariolinkII
Transparent, VariolinkII-Transparent (base), Nexus, RelyX Unicem, RelyX ultimate,
Duolink, Monocem and Resinomer) and longitudinal sections of same thickness were
obtained from molar and premolar. Specimens were assigned to two groups one had
molar section with 10 specimens whereas other had premolar with remaining 10
specimens. Each group was placed on digital radiograph sensor (Schick CDR, size
2) together with aluminum step-wedge. Sensor was exposed to X-ray using standard
technique. Two images were obtained for each group. Pixel measurements were made
using NIH Image-J software. Mean pixel measurements were converted into aluminum
thickness equivalents. Data were statistically-analyzed using one-way ANOVA and
Tukey's tests. RESULTS: ANOVA revealed significant difference in mean pixel
values among cements (p < 0.001). VariolinkII-opaque showed highest mean aluminum
equivalent (4.6 mm Al/1 mm) followed by VariolinkII-opaque-Base (4.5 mm Al/1 mm),
VariolinkII-transparent (4.45 mm Al/1 mm), VariolinkII-transparent-Base (4.45 mm
Al/1 mm), Nexus (2.95 mm Al/1 mm), Duolink (2.7 mm Al/1 mm), RelyX Unicem (2.2 mm
Al/1 mm) and finally RelyX ultimate (2 mm Al/1 mm). All cements had mean
radiopacity values higher than that of enamel whereas Monocem (1.25 mm Al/1 mm)
and Resinomer (1.2 mm Al/1 mm) had means between those of enamel and dentin.
CONCLUSIONS: All tested resin-cements showed radiopacity values higher than that
of dentin which is adequate for diagnostic purposes according to ISO
recommendation. CLINICAL SIGNIFICANCE: The use of resin cement with adequate
radiopacity for adhesive cementation of glass-ceramic based restorations enables
their radiographic monitoring. (J Esthet Restor Dent 29:215-221, 2017).
PMID- 28417582
TI - Hierarchical TiO2 /SnO2 Hollow Spheres Coated with Graphitized Carbon for High
Performance Electrochemical Li-Ion Storage.
AB - A self-templated strategy is developed to fabricate hierarchical TiO2 /SnO2
hollow spheres coated with graphitized carbon (HTSO/GC-HSs) by combined sol-gel
processes with hydrothermal treatment and calcination. The as-prepared mesoporous
HTSO/GC-HSs present an approximate yolk-double-shell structure, with high
specific area and small nanocrystals of TiO2 and SnO2 , and thus exhibit superior
electrochemical reactivity and stability when used as anode materials for Li-ion
batteries. A high reversible specific capacity of about 310 mAh g-1 at a high
current density of 5 A g-1 can be achieved over 500 cycles indicating very good
cycle stability and rate performance.
PMID- 28417583
TI - Ethnic differences in the pathogenesis of obstructive sleep apnoea: Exploring non
anatomical factors.
PMID- 28417584
TI - IR-spectroscopy of skin in vivo: Optimal skin sites and properties for non
invasive glucose measurement by photoacoustic and photothermal spectroscopy.
AB - We have reported two methods to analyze glucose in the interstitial fluid of skin
based on mid-infrared excitation with a tunable quantum cascade laser and
photoacoustic or photothermal detection. These methods were evaluated for optimum
skin locations to obtain reproducible glucose information. The lower part of the
arm, the hypothenar, the tips of the index finger and the thumb were tested. The
thumb appears to be the optimal skin location, followed by the index finger.
Basic requirements for an optimum site are good capillary blood perfusion, low
Stratum corneum thickness and the absence of fat layers. To obtain a correlation
on such a site, spectra were recorded on volunteers continuously after blood
glucose manipulation. However, continuous measurements on an in vivo sample such
as the skin have to cope with physiological alterations such as the formation of
sweat. We have used both detection schemes to investigate the acid mantle
reformation after washing during time scales similar to continuous measurements
for calibration spectra. We found that reconstitution of the acid mantle of skin
may be seen in less than one hour. Precleaning of the measurement site may thus
be useful for intermittent, but not for long term continuous measurements.
PMID- 28417585
TI - Speckle variance optical coherence tomography of blood flow in the beating mouse
embryonic heart.
AB - Efficient separation of blood and cardiac wall in the beating embryonic heart is
essential and critical for experiment-based computational modelling and analysis
of early-stage cardiac biomechanics. Although speckle variance optical coherence
tomography (SV-OCT) relying on calculation of intensity variance over
consecutively acquired frames is a powerful approach for segmentation of fluid
flow from static tissue, application of this method in the beating embryonic
heart remains challenging because moving structures generate SV signal
indistinguishable from the blood. Here, we demonstrate a modified four
dimensional SV-OCT approach that effectively separates the blood flow from the
dynamic heart wall in the beating mouse embryonic heart. The method takes
advantage of the periodic motion of the cardiac wall and is based on calculation
of the SV signal over the frames corresponding to the same phase of the heartbeat
cycle. Through comparison with Doppler OCT imaging, we validate this speckle
based approach and show advantages in its insensitiveness to the flow direction
and velocity as well as reduced influence from the heart wall movement. This
approach has a potential in variety of applications relying on visualization and
segmentation of blood flow in periodically moving structures, such as mechanical
simulation studies and finite element modelling. Picture: Four-dimensional
speckle variance OCT imaging shows the blood flow inside the beating heart of an
E8.5 mouse embryo.
PMID- 28417586
TI - ICU mortality is increased with high admission serum osmolarity in all patients
other than those admitted with pulmonary diseases and hypoxia.
AB - BACKGROUND AND OBJECTIVE: High serum osmolarity has been shown to be lung
protective. There is lack of clinical studies evaluating the impact on outcomes
such as mortality. We aimed to examine the effect of serum osmolarity on
intensive care unit (ICU) mortality in critically ill patients METHODS: Data from
January 2000 to December 2012 was accessed using the Australian and New Zealand
Intensive Care Society (ANZICS) Clinical Outcomes and Resource Evaluation (CORE)
database. A total of 509 180 patients were included. Serum osmolarity was
calculated from data during the first 24 h of ICU admission. Predefined subgroups
(Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic codes),
including patients with acute pulmonary diagnoses, were examined. The effect of
serum osmolarity on ICU mortality was assessed with analysis adjusted for illness
severity (serum sodium, glucose and urea component removed) and year of
admission. Results are presented as OR (95% CI) referenced against a serum
osmolarity of 290-295 mmol/L. RESULTS: The ICU mortality was elevated at each
extremes of serum osmolarity (U-shaped relationship). A similar relationship was
found in various subgroups, with the exception of patients with pulmonary
diagnoses in whom ICU mortality was not influenced by high serum osmolarity and
was different from other non-pulmonary subgroups (P < 0.01). Any adverse
associations with high serum osmolarity in pulmonary patients were confined to
patients with a PaO2 /FiO2 ratio > 200. CONCLUSION: High admission serum
osmolarity was not associated with increased odds for ICU death in pulmonary
patients, unlike other subgroup of patients, and could be a potential area for
future interventional therapy.
PMID- 28417587
TI - Healthcare utilization and spending by children with cancer on Medicaid.
AB - BACKGROUND: Children with cancer are a unique patient population with high
resource, complex healthcare needs. Understanding their healthcare utilization
could highlight areas for care optimization. PROCEDURE: We performed a
retrospective, cross-sectional analysis of the 2014 Truven Marketscan Medicaid
Database to explore clinical attributes, utilization, and spending among children
with cancer who were Medicaid enrollees. Eligible patients included children
(ages 0-18 years) with cancer (Clinical Risk Group 8). Healthcare utilization and
spending (per member per month, PMPM) were assessed overall and across specific
healthcare services. RESULTS: Children with cancer (n = 5,405) represent less
than 1% of the 1,516,457 children with medical complexity in the dataset.
Children with cancer had high services use: laboratory/radiographic testing
(93.0%), outpatient specialty care (83.4%), outpatient therapy/treatment (53.4%),
emergency department (43.7%), hospitalization (31.5%), home healthcare (9.5%).
PMPM spending for children with cancer was $3,706 overall and $2,323 for hospital
care. CONCLUSION: Children with cancer have high healthcare resource use and
spending. Differences in geographic distribution of services for children with
cancer and the trajectory of spending over the course of therapy are areas for
future investigation aimed at lowering costs of care without compromising on
health outcomes.
PMID- 28417588
TI - A Scalable and Versatile Synthesis of Oxime-Based Hormone Dimers and Gels for
Sustained Release.
AB - Well-defined steroid hormone dimers and organogels were produced via a facile and
scalable synthesis using oxime click chemistry. The versatile synthetic procedure
extends to a wide range of hormones and linker groups exemplified here through
the synthesis of cortisol- and progesterone-dimers linked via hydrophobic,
hydrophilic or functional groups. This method was also extended to the synthesis
of cortisone-based organogels. Owing to the dynamic nature of the oxime bond, the
hormone-based materials are degradable via acidic hydrolysis and transoximination
representing new materials for the controlled release of steroid hormones.
PMID- 28417589
TI - Glutathione-stabilized Cu nanocluster-based fluorescent probe for sensitive and
selective detection of Hg2+ in water.
AB - In this paper, an innovative and facile one-pot method for synthesizing water
soluble and stable fluorescent Cu nanoclusters (CuNCs), in which glutathione
(GSH) served as protecting ligand and ascorbic acid (AA) as reducing agent was
reported. The resultant CuNCs emitted blue-green fluorescence at 440 nm, with a
quantum yield (QD) of about 3.08%. In addition, the prepared CuNCs exhibited
excellent properties such as good water solubility, photostability and high
stability toward high ionic strength. On the basis of the selective quenching of
Hg2+ on CuNCs fluorescence, which may be the result of Hg2+ ion-induced
aggregation of the CuNCs, the CuNCs was used for the selective and sensitive
determination of Hg2+ in aqueous solution. The proposed analytical strategy
permitted detection of Hg2+ in a linear range of 4 * 10-8 to 6 * 10-5 M, with a
detection limit of 2.2 * 10-8 M. Eventually, the practicability of this sensing
approach was confirmed by its successful application to assay Hg2+ in tap water,
Lotus lake water and river water samples with the quantitative spike recoveries
ranging from 96.9% to 105.4%.
PMID- 28417590
TI - Calcitonin gene-related peptide (CGRP): A novel target for Alzheimer's disease.
AB - Alzheimer's disease (AD) is leading cause of death among older characterized by
neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and
increased levels of amyloid-beta (Abeta) peptides. Cholinergic treatment could be
the best suitable physiological therapy for AD. Calcitonin gene-related peptide
(CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from
different merging of the CGRP gene, which also includes adrenomedullin, amylin,
calcitonin, intermedin, and calcitonin receptor-stimulating peptide. It is a
proof for a CGRP receptor within nucleus accumbens of brain that is different
from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high
affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is
not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases
activated cAMP-dependent pkA and PI3 kinase, resulting in N-terminal fragments
that are shown to exert complex inhibitory as well facilitator actions on nAChRs.
Fragments such as CGRP1-4, CGRP1-5, and CGRP1-6 rapidly as well as reversibly
improve agonist sensitivity of nAChRs without straight stimulating those
receptors and produce the Ca2+ -induced intracellular Ca2+ mobilization. Renin
angiotensin-aldosterone system (RAAS)-activated angiotensin-type (AT4) receptor
is also beneficial in AD. It has been suggested that exogenous administration of
CGRP inhibits infiltration of macrophages and expression of various inflammatory
mediators such as NFkB, IL-1b, TNF-alpha, iNOS, matrix metalloproteinase (MMP)-9,
and cell adhesion molecules like intercellular adhesion molecule (ICAM)-1 which
attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits
acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate
gyrus of the hippocampus of WT mice after donepezil administration. However, none
of the results discovered in CGRP-knockout mice and WT mice exposed to practical
denervation. Therefore, selective agonists of CGRP receptors may become the
potential candidates for treatment of AD.
PMID- 28417591
TI - Effective mosquito and arbovirus surveillance using metabarcoding.
AB - Effective vector and arbovirus surveillance requires timely and accurate
screening techniques that can be easily upscaled. Next-generation sequencing
(NGS) is a high-throughput technology that has the potential to modernize vector
surveillance. When combined with DNA barcoding, it is termed 'metabarcoding.' The
aim of our study was to establish a metabarcoding protocol to characterize pools
of mosquitoes and screen them for virus. Pools contained 100 morphologically
identified individuals, including one Ross River virus (RRV) infected mosquito,
with three species present at different proportions: 1, 5, 94%. Nucleic acid
extracted from both crude homogenate and supernatant was used to amplify a 269-bp
section of the mitochondrial cytochrome c oxidase subunit I (COI) locus.
Additionally, a 67-bp region of the RRV E2 gene was amplified from synthesized
cDNA to screen for RRV. Amplicon sequencing was performed using an Illumina
MiSeq, and bioinformatic analysis was performed using a DNA barcode database of
Victorian mosquitoes. Metabarcoding successfully detected all mosquito species
and RRV in every positive sample tested. The limits of species detection were
also examined by screening a pool of 1000 individuals, successfully identifying
the species and RRV from a single mosquito. The primers used for amplification,
number of PCR cycles and total number of individuals present all have effects on
the quantification of species in mixed bulk samples. Based on the results, a
number of recommendations for future metabarcoding studies are presented.
Overall, metabarcoding shows great promise for providing a new alternative
approach to screening large insect surveillance trap catches.
PMID- 28417593
TI - Anomalous Resistance Hysteresis in Oxide ReRAM: Oxygen Evolution and
Reincorporation Revealed by In Situ TEM.
AB - The control and rational design of redox-based memristive devices, which are
highly attractive candidates for next-generation nonvolatile memory and logic
applications, is complicated by competing and poorly understood switching
mechanisms, which can result in two coexisting resistance hystereses that have
opposite voltage polarity. These competing processes can be defined as regular
and anomalous resistive switching. Despite significant characterization efforts,
the complex nanoscale redox processes that drive anomalous resistive switching
and their implications for current transport remain poorly understood. Here,
lateral and vertical mapping of O vacancy concentrations is used during the
operation of such devices in situ in an aberration corrected transmission
electron microscope to explain the anomalous switching mechanism. It is found
that an increase (decrease) in the overall O vacancy concentration within the
device after positive (negative) biasing of the Schottky-type electrode is
associated with the electrocatalytic release and reincorporation of oxygen at the
electrode/oxide interface and is responsible for the resistance change. This
fundamental insight presents a novel perspective on resistive switching processes
and opens up new technological opportunities for the implementation of memristive
devices, as anomalous switching can now be suppressed selectively or used
deliberately to achieve the desirable so-called deep Reset.
PMID- 28417595
TI - Influence of demographic characteristics on attenuated positive psychotic
symptoms in a young, help-seeking, at-risk population.
AB - AIM: Presentation of attenuated positive psychotic symptoms (APS) was reported to
be modestly influenced by age, sex and education in a psychosis-risk sample. We
re-examined the influence of demographic variables on APS in an independent
psychosis-risk sample. METHOD: In a clinical high-risk-sample (N = 188; 13-35
years; 60.1% men), bivariate correlations were examined with Spearman
correlations. All other associations were computed with generalized linear
models. RESULTS: Inter-correlations between positive symptoms were statistically
significant for all but the smallest coefficient (range: r = 0.12-0.49). Age was
negatively related to APS (range: OR = 0.53-0.78, all P < .01). Male sex was
uniquely related to disorganized communication (OR = 1.46) and a high education
level related negatively to suspiciousness/persecutory ideas (OR = 0.64),
perceptual abnormalities/hallucinations (OR = 0.57) and disorganized
communication (OR = 0.54). The variance explained by age ranged from R 2 = 0.044
for unusual thought content to R 2 = 0.144 for perceptual abnormalities.
CONCLUSION: Our results highlighted the role of age and, thereby,
neurodevelopment in psychosis-risk assessment.
PMID- 28417594
TI - Real-world supported unprotected left main percutaneous coronary intervention
with impella device; data from the USpella registry.
AB - BACKGROUND: Patients with left main (LM) coronary artery disease are increasingly
being treated with percutaneous revascularization (PCI). The safety, feasibility,
and efficacy of unprotected LM intervention (ULMI) with hemodynamic support by
Impella device have not been evaluated previously. OBJECTIVE: Using a large
retrospective single center database from the USpella registry, we evaluated the
safety, feasibility, and potential benefits of periprocedural left ventricular
assist with axial flow Impella 2.5 and Impella CP (Abiomed Inc. Danvers, Mass)
during ULMI. METHODS: We analyzed a total of 127 consecutive patients who
received hemodynamic support with Impella (2.5 or CP) for ULMI from August 2008
to July 2015. Safety, feasibility and efficacy end points included procedural
success rates, in-hospital and 30-day major adverse cardiovascular event (MACE)
rates. RESULTS: Among 127 patients who received hemodynamic support for ULMI
(mean age 69.98 +/- 10.7 years, 71% men, and mean left ventricular ejection
fraction 28.74 +/- 15.55%, Society of Thoracic Surgeons' mortality/morbidity
4/23%) the in-hospital and 30 days mortality rates were 1.43% (2/140) and 2.1%
(3/141), respectively. The average baseline and post PCI (residual) syntax scores
were 31.4 and 7.86, respectively, (P < 0.001). Only one patient (0.8%) had
vascular complication that required surgery; 2.36% (3/127) had hematoma and 3.9%
(5/127) had bleeding that required transfusion. CONCLUSION: This large singe
center retrospective evaluation of USpella registry substantiates and strongly
supports the feasibility, safety, and hemodynamic usefulness of Impella device
for ULMI with acceptable in-hospital and 30-day MACE rates. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28417592
TI - Individualising the dose of allopurinol in patients with gout.
AB - AIMS: The aims of the study were to: 1) determine if a plasma oxypurinol
concentration-response relationship or an allopurinol dose-response relationship
best predicts the dose requirements of allopurinol in the treatment of gout; and
2) to construct a nomogram for calculating the optimum maintenance dose of
allopurinol to achieve target serum urate (SU) concentrations. METHODS: A
nonlinear regression analysis was used to examine the plasma oxypurinol
concentration- and allopurinol dose-response relationships with serum urate. In
81 patients (205 samples), creatinine clearance (CLCR ), concomitant diuretic use
and SU concentrations before (UP ) and during (UT ) treatment were monitored
across a range of allopurinol doses (D, 50-700 mg daily). Plasma concentrations
of oxypurinol (C) were measured in 47 patients (98 samples). Models (n = 47
patients) and predictions from each relationship were compared using F-tests, r2
values and paired t-tests. The best model was used to construct a nomogram.
RESULTS: The final plasma oxypurinol concentration-response relationship (UT =
UP - C*(UP - UR )/(ID50 + C), r2 = 0.64) and allopurinol dose-response
relationship (UT = UP - D* (UP - UR )/(ID50 + D), r2 = 0.60) did not include
CLCR or diuretic use as covariates. There was no difference (P = 0.87) between
the predicted SU concentrations derived from the oxypurinol concentration- and
allopurinol dose-response relationships. The nomogram constructed using the
allopurinol dose-response relationship for all recruited patients (n = 81
patients) required pretreatment SU as the predictor of allopurinol maintenance
dose. CONCLUSIONS: Plasma oxypurinol concentrations, CLCR and diuretic status are
not required to predict the maintenance dose of allopurinol. Using the nomogram,
the maintenance dose of allopurinol estimated to reach target concentrations can
be predicted from UP .
PMID- 28417596
TI - Compressing Carbon Nanocages by Capillarity for Optimizing Porous Structures
toward Ultrahigh-Volumetric-Performance Supercapacitors.
AB - High volumetric energy density combined with high power density is highly desired
for electrical double-layer capacitors. Usually the volumetric performance is
improved by compressing carbon material to increase density but at the much
expense of power density due to the deviation of the compressed porous structure
from the ideal one. Herein the authors report an efficient approach to increase
the density and optimize the porous structure by collapsing the carbon nanocages
via capillarity. Three samples with decreasing sizes of meso- and macropores
provide us an ideal model system to demonstrate the correlation of volumetric
performance with porous structure. The results indicate that reducing the surplus
macropores and, more importantly, the surplus mesopores is an efficient strategy
to enhance the volumetric energy density while keeping the high power density.
The optimized sample achieves a record-high stack volumetric energy density of 73
Wh L-1 in ionic liquid with superb power density and cycling stability.
PMID- 28417597
TI - Ultrahigh-Water-Content, Superelastic, and Shape-Memory Nanofiber-Assembled
Hydrogels Exhibiting Pressure-Responsive Conductivity.
AB - High-water-content hydrogels that are both mechanically robust and conductive
could have wide applications in fields ranging from bioengineering and electronic
devices to medicine; however, creating such materials has proven to be extremely
challenging. This study presents a scalable methodology to prepare superelastic,
cellular-structured nanofibrous hydrogels (NFHs) by combining alginate and
flexible SiO2 nanofibers. This approach causes naturally abundant and sustainable
alginate to assemble into 3D elastic bulk NFHs with tunable water content and
desirable shapes on a large scale. The resultant NFHs exhibit the integrated
properties of ultrahigh water content (99.8 wt%), complete recovery from 80%
strain, zero Poisson's ratio, shape-memory behavior, injectability, and elastic
responsive conductivity, which can detect dynamic pressure in a wide range (>50
Pa) with robust sensitivity (0.24 kPa-1 ) and durability (100 cycles). The
fabrication of such fascinating materials may provide new insights into the
design and development of multifunctional hydrogels for various applications.
PMID- 28417599
TI - High Dielectric Performances of Flexible and Transparent Cellulose Hybrid Films
Controlled by Multidimensional Metal Nanostructures.
AB - Various wearable electronic devices have been developed for extensive outdoor
activities. The key metrics for these wearable devices are high touch sensitivity
and good mechanical and thermal stability of the flexible touchscreen panels
(TSPs). Their dielectric constants (k) are important for high touch
sensitivities. Thus, studies on flexible and transparent cover layers that have
high k with outstanding mechanical and thermal reliabilities are essential.
Herein, an unconventional approach for forming flexible and transparent cellulose
nanofiber (CNF) films is reported. These films are used to embed ultralong metal
nanofibers that serve as nanofillers to increase k significantly (above 9.2 with
high transmittance of 90%). Also, by controlling the dimensions and aspect ratios
of these fillers, the effects of their nanostructures and contents on the optical
and dielectric properties of the films have been studied. The length of the
nanofibers can be controlled using a stretching method to break the highly
aligned, ultralong nanofibers. These nanofiber-embedded, high-k films are
mechanically and thermally stable, and they have better Young's modulus and
tensile strength with lower thermal expansion than commercial transparent
plastics. The demonstration of highly sensitive TSPs using high-k CNF film for
smartphones suggests that this film has significant potential for next
generation, portable electronic devices.
PMID- 28417598
TI - Genetic analysis of a morphologically heterogeneous ovarian endometrioid
carcinoma.
AB - AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade
components. Whether the latter are clonally related to and originate from the low
grade endometrioid carcinoma remains unclear. The aim of this study was to use
massively parallel sequencing to characterize the genomic landscape and clonal
relatedness of an ovarian endometrioid carcinoma containing low-grade and high
grade components. METHODS AND RESULTS: DNA samples extracted from each tumour
component (low-grade endometrioid, high-grade anaplastic and high-grade squamous)
and matched normal tissue were subjected to targeted massively parallel
sequencing with the 410-gene Memorial Sloan Kettering-Integrated Mutation
Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. Somatic
single nucleotide variants, small insertions and deletions, and copy number
alterations were detected with state-of-the-art bioinformatics algorithms, and
validated with orthogonal methods. The endometrioid carcinoma and the associated
high-grade components shared copy number alterations and four clonal mutations,
including SMARCA4 mutations, which resulted in loss of BRG1 protein expression.
Subclonal mutations and mutations restricted to single components were also
identified, such as distinct TP53 mutations restricted to each histological
component. CONCLUSIONS: Histologically distinct components of ovarian
endometrioid carcinomas may show intratumour genetic heterogeneity but be
clonally related, harbouring a complex clonal composition. In the present case,
SMARCA4 mutations were probably early events, whereas TP53 somatic mutations were
acquired later in evolution.
PMID- 28417601
TI - Abstracts of the Seventh Annual Meeting of the Associazione Italiana Sistema
Nervoso Periferico (ASNP) April 20-22, 2017 Bergamo, Italy.
PMID- 28417600
TI - A Bioinspired Mineral Hydrogel as a Self-Healable, Mechanically Adaptable Ionic
Skin for Highly Sensitive Pressure Sensing.
AB - In the past two decades, artificial skin-like materials have received increasing
research interests for their broad applications in artificial intelligence,
wearable devices, and soft robotics. However, profound challenges remain in terms
of imitating human skin because of its unique combination of mechanical and
sensory properties. In this work, a bioinspired mineral hydrogel is developed to
fabricate a novel type of mechanically adaptable ionic skin sensor. Due to its
unique viscoelastic properties, the hydrogel-based capacitive sensor is
compliant, self-healable, and can sense subtle pressure changes, such as a gentle
finger touch, human motion, or even small water droplets. It might not only show
great potential in applications such as artificial intelligence, human/machine
interactions, personal healthcare, and wearable devices, but also promote the
development of next-generation mechanically adaptable intelligent skin-like
devices.
PMID- 28417602
TI - Novel use of perfusion balloon inflation to avoid outflow tract obstruction
during transcatheter mitral valve-in-valve replacement.
AB - Left ventricular outflow tract (LVOT) obstruction is a recognized complication of
transcatheter mitral valve-in-valve replacement in previous surgical prostheses.
We describe a patient who was high risk for repeat open surgery in whom the LVOT
was compromised by a surgical strut and the potential for LVOT obstruction. A
novel approach to avoiding this complication was utilized. A perfusion balloon
was inflated in the outflow tract to provide an opposing force during mitral
valve deployment resulting in less flaring of the strut into the outflow tract
thereby improving the neo-LVOT area. No outflow tract obstruction occurred. The
advantages of this approach as well as other alternative solutions to this
problem are discussed. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417603
TI - Squamate Conserved Loci (SqCL): A unified set of conserved loci for phylogenomics
and population genetics of squamate reptiles.
AB - The identification of conserved loci across genomes, along with advances in
target capture methods and high-throughput sequencing, has helped spur a
phylogenomics revolution by enabling researchers to gather large numbers of
homologous loci across clades of interest with minimal upfront investment in
locus design. Target capture for vertebrate animals is currently dominated by two
approaches-anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)-and
both approaches have proven useful for addressing questions in phylogenomics,
phylogeography and population genomics. However, these two sets of loci have
minimal overlap with each other; moreover, they do not include many traditional
loci that that have been used for phylogenetics. Here, we combine across UCE, AHE
and traditional phylogenetic gene locus sets to generate the Squamate Conserved
Loci set, a single integrated probe set that can generate high-quality and highly
complete data across all three loci types. We use these probes to generate data
for 44 phylogenetically disparate taxa that collectively span approximately 33%
of terrestrial vertebrate diversity. Our results generated an average of 4.29 Mb
across 4709 loci per individual, of which an average of 2.99 Mb was sequenced to
high enough coverage (>=10*) to use for population genetic analyses. We validate
the utility of these loci for both phylogenomic and population genomic questions,
provide a comparison among these locus sets of their relative usefulness and
suggest areas for future improvement.
PMID- 28417604
TI - Rotational atherectomy in the subadventitial space to allow safe and successful
chronic total occlusion recanalization: Pushing the limit further.
AB - Dissection and re-entry (DR) techniques have played a key role in the increase of
success rates of chronic total occlusion (CTO) recanalization. DR usually allows
wiring complex occlusions, even in case of important calcification. In extreme
cases, such as in balloon failure-to-cross, rotational atherectomy (RA) might be
decisive. However, according to experts' recommendations, RA should not be
performed in dissection planes because of the high risk of perforation and
further extending the dissection, so that its use after DR might be limited.
Here, we describe a case of successful right coronary artery CTO recanalization
in which, after failure of several antegrade and retrograde techniques, RA was
safely performed antegradely in the subadventitial space, thus eventually
enabling reverse controlled antegrade and retrograde subintimal tracking (CART).
Although the feasibility of RA in CTO percutaneous coronary intervention had
already been suggested, this case reports on the novel use of RA to allow further
manipulation of the subadventitial space (reverse CART) prior to successful
recanalization. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417607
TI - Rebuttal: Adverse outcome of coarctation stenting in patients with Turner
syndrome.
PMID- 28417606
TI - Caboxamycin biosynthesis pathway and identification of novel benzoxazoles
produced by cross-talk in Streptomyces sp. NTK 937.
AB - Streptomyces sp. NTK937, producer of benzoxazole antibiotic caboxamycin, produces
in addition a methyl ester derivative, O-methylcaboxamycin. Caboxamycin cluster,
comprising one regulatory and nine structural genes, has been delimited, and each
gene has been individually inactivated to demonstrate its role in the
biosynthetic process. The O-methyltransferase potentially responsible for O
methylcaboxamycin synthesis would reside outside this cluster. Five of the genes,
cbxR, cbxA, cbxB, cbxD and cbxE, encoding a SARP transcriptional regulator,
salicylate synthase, 3-oxoacyl-ACP-synthase, ACP and amidohydrolase,
respectively, have been found to be essential for caboxamycin biosynthesis. The
remaining five structural genes were found to have paralogues distributed
throughout the genome, capable of partaking in the process when their cluster
homologue is inactivated. Two of such paralogues, cbxC' and cbxI', coding an AMP
dependent synthetase-ligase and an anthranilate synthase, respectively, have been
identified. However, the other three genes might simultaneously have more than
one paralogue, given that cbxF (DAHP synthase), cbxG (2,3-dihydro-2,3
dihydroxybenzoate dehydrogenase) and cbxH (isochorismatase) have three, three and
five putative paralogue genes, respectively, of similar function within the
genome. As a result of genetic manipulation, a novel benzoxazole (3'
hydroxycaboxamycin) has been identified in the salicylate synthase-deficient
mutant strain DeltacbxA. 3'-hydroxycaboxamycin derives from the cross-talk
between the caboxamycin and enterobactin pathways.
PMID- 28417608
TI - Comparison of antithrombotic agents during urgent percutaneous coronary
intervention following thrombolytic therapy: A retrospective cohort study.
AB - BACKGROUND: The optimal antithrombotic regimen for urgent percutaneous coronary
interventions (PCI) following thrombolytic therapy for ST segment myocardial
infarction (STEMI) is currently unknown. METHODS: We performed a retrospective
analysis of all patients referred to our institution from January 2005 to July
2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy.
The patients were divided into three cohorts based on the anticoagulation
strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein
IIb/IIIa inhibitor (GPI). The primary end point of major adverse cardiovascular
events (MACE) was defined as a composite of inpatient death, myocardial
infarction (MI) and stroke. Net adverse clinical events (NACE) were defined as a
combination of MACE plus major bleeding complications. Univariable, multivariable
and propensity-weighted modeling were used to compare MACE and NACE between the
three treatment groups. RESULTS: A total of 695 patients met the inclusion
criteria during the study period. In the univariable analysis, there was no
significant difference treatment in MACE between the three groups (Bivalirudin:
1.2% vs. Heparin + GPI: 4.4%; Heparin alone: 2.7%, P = 0.11). In the reduced
logistic regression model, compared to bivalirudin, the odds of NACE was
significantly higher with heparin alone (OR: 3.58, 95% CI: 1.21, 10.54, P = 0.02)
or with heparin plus GPI (OR: 9.0, 95% CI: 2.83, 28.64, P <0.001). CONCLUSION: In
STEMI patients undergoing PCI within 24 hr after thrombolytic therapy,
bivalirudin was associated with a strong trend toward reduced bleeding
complications as compared to heparin alone or heparin plus GPI. The optimal
antithrombotic regiment for urgent PCI following thrombolytic therapy is
currently unknown. Our study demonstrated that use of bivalirudin during PCI
following thrombolytic therapy is associated with a trend toward reduced bleeding
complications compared to heparin alone or heparin plus GPI. Large randomized
trials of adjunctive anticoagulation during PCI in this complex post-thrombolytic
population are warranted. (c) 2017 Wiley Periodicals, Inc.
PMID- 28417609
TI - Action plans and coping strategies in elderly COPD patients influence the result
of pulmonary rehabilitation: an observational study.
AB - BACKGROUND: COPD management needs a comprehensive assessment of clinical features
(symptoms severity, co-morbidities) together with life-style, behavioural, socio
economic and multi-omics parameters. Among the other issues, psycho-cognitive
assessment plays a critical role. Coping strategies are used to manage
psychological stress. AIM: To evaluate the association between coping strategies
and outcome of Pulmonary Rehabilitation (PR). DESIGN: Observational study.
SETTING: Inpatients comprehensive 3 weeks PR programme. POPULATION: Seventy-six
patients, 70 years or older affected by COPD GOLD 3-4. METHODS: Disease-specific
status was examined using the Medical Research Council Dyspnea Scale, St.
George's Respiratory Questionnaire, Maugeri Respiratory Failure, Borg And Barthel
Scales. Cognitive And Psychological Clinical Alterations/Disorders Using: Mini
Mental State Examination; Montreal Cognitive Assessment; Center for Epidemiologic
Studies Depression Scale; Zung Self-Rating Anxiety Scale. Quality of Life Using
Activities of Daily Living; Instrumental Activities of Daily Living; 36-Item
Short Form Health Survey General and Mental Health. Functional exercise capacity
was measured at baseline and after PR using the Six-Minute Walking Test (6MWT).
Coping strategies were measured with the Brief COPE. Internal consistency was
determined examining Cronbach's alpha values. Concurrent validity was determined
by examining Spearman r correlations between the single-item and multi-items.
Brief-COPE scores after PR between patients who had a different response to
respiratory outcomes was evaluated using Student's t and Mann-Whitney U tests.
RESULTS: The change in distance (Delta6MWD) between final and baseline value in
meters was positively associated with Self-distraction, Active Coping, and
Planning strategies. Respiratory disease-specific health status outcomes, as well
as the presence of use of long-term oxygen therapy, were not associated with
coping strategies. CONCLUSIONS: Self-distraction and Planning strategies are
associated to the success of rehabilitation. CLINICAL REHABILITATION IMPACT: Self
distraction and Planning strategies may predict response to pulmonary
rehabilitation in elderly patients affected by severe COPD.
PMID- 28417610
TI - Functional outcome of critical illness polyneuropathy in patients affected by
severe brain injury.
AB - BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) frequently occur
in intensive care unit (ICU) critically ill subjects; about 55-70% of subjects
achieve full recovery. CIPNM can occur in ICU subjects with severe acquired brain
injury (sABI), but no data have been reported regarding their outcome. AIM: The
aim of the present study was to investigate the functional recovery in subjects
suffering from both CIPNM and sABI and whether they had poorer outcome than those
with sABI only. DESIGN: Prospective cohort study. SETTING: Dedicated
rehabilitation setting. POPULATION: Adult ICU subjects with sABI causing a
disorder of consciousness graded 3-8 on the Glasgow Coma Scale admitted to a
dedicated rehabilitative setting were enrolled from January 2015 to June 2016.
METHODS: The enrolled sample was divided in two groups: patients with CIPNM and
coexistent sABI (CIPNM+sABI) and patients with sABI. Electromyography was
performed in all subjects to ascertain CIPNM occurrence, at admission. Functional
outcome was investigated using the Rancho Los Amigos Levels of Cognitive
Functioning (LCF), Disability Rating Scale (DRS), Glasgow Outcome Scale (GOS) and
modified Rankin Scale (mRS), at admission and discharge. Mortality and length of
stay (LOS) were recorded. RESULTS: One-hundred and thirty-one patients (59 F, 72
M; mean age 54.7+/-15.8) were admitted to the rehabilitation setting, and 111 (47
F, 64 M; mean age: 53.6+/-18.4 years) were enrolled. Thirty-six (31.8%) had
CIPNM+sABI, and 75 patients had isolated sABI. Significant functional outcomes in
all assessment measures were observed after rehabilitation in all samples. The
estimated mean scores (95% confidence interval) of LCF, DRS, GOS and mRS from a
multivariate model adjusted for age, sex and time of ICU stay were: 2.85 (2.53
3.21) and 5.24 (4.81-5.71), 23.94 (22.37-25.62) and 16.04 (14.77-17.41), 2.86
(2.70-3.04) and 3.46 (3.28-3.65), and 4.91 (4.67-5.17) and 3.79 (3.58-4.02), at
admission and at discharge, respectively. Despite functional improvement,
CIPNM+sABI patients showed lesser improvement than those with sABI only.
Furthermore, patients with both disorders had significantly higher median LOS
than sABI subjects: 107 (q1-q3: 65-146), and 65 (q1-q3: 38-105) days (P=5.5x10
83), respectively. No statistically significant difference in mortality rates was
found between groups. CONCLUSIONS: Subjects with CIPNM and coexistent sABI
improved after rehabilitation, but had poorer recovery than those with solely
sABI requiring a longer LOS. CLINICAL REHABILITATION IMPACT: The rehabilitation
process in subjects suffering from CINPM is challenging and no evidence support
the use of specific rehabilitative approaches to improve function and activities
of daily living.
PMID- 28417611
TI - Factors enhancing activities of daily living after stroke in specialized
rehabilitation: an observational multicenter study within the Sunnaas
International Network.
AB - BACKGROUND: Stroke may lead to serious, long-term disability. Consequently, many
individuals with stroke will be in need of rehabilitation, and some of
specialized rehabilitation. The content and organization of rehabilitation vary
within and between countries, reflecting the preferences, customs, traditions,
and values of a society or community, that may have an impact on outcomes. The
main aim of the present study was to evaluate the influence of team models in
specialized rehabilitation on outcomes as measured by stroke patients'
performance in activities of daily living (ADL), at a standardized time and at
discharge in the various specialized rehabilitation clinics. Secondary aims were
to identify explanatory factors for possible differences in ADL changes at
standardized time points. DESIGN: A prospective descriptive cross-sectional
explorative, multicenter study. SETTING: Specialized rehabilitation clinics in
Norway, China, the USA, Russia, Israel, Palestine, and Sweden, for a total of
nine clinics. POPULATION: Persons with stroke. METHODS: Outcomes measures were
the modified Rankin Scale (mRS) and the National Institute of Health Stroke Scale
(NIHSS), both on admission and at discharge from the inpatient rehabilitation
unit, and Barthel Index (BI) or alternatively Functional Independence Measure
(FIM), on admittance, 18-22 days into rehabilitation, at discharge, and at 6 and
12 months after discharge. RESULTS: In total 230 stroke patients from nine
clinics were recruited. There were significant differences in change scores of
ADL from admittance to standardized time point 18-22 days into rehabilitation,
(P<0.001, R2=0.19) and when controlled for baseline NIHSS and mRS (P<0.001,
R2=0.18; P=0.01, R2=0.9 respectively). Analysis divided into intra-, multi- and
interdisciplinary models showed significant differences at 18-22 days (P=0.02)
and at discharge (P<0.001), indicating a more favorable outcome in ADL with the
multi-disciplinary model. The linear regression analysis explained 55% of the
changes in ADL (R2=0.55) at the standardized time point and 48% (R2=0.48) at
discharge. Main explanatory factors were disability (mRS) and severity (NIHSS),
team models, hours in therapy, and location at discharge. ADL was maintained for
the majority of participants at 6 and 12 months post discharge. The correlations
mRS/ADL (r=-0.68, P<0.0001), NIHSS/ADL (r=-0.55, P<0.0001) and NIHSS/mRS (r=0.46,
P<0.0001) disclosed medium to large associations at 18-22 days into
rehabilitation. CONCLUSIONS: The study indicates that the organization of
services in specialized rehabilitation after stroke has a major impact on
improvement of ADL outcomes. Main positive predictive factors were models of
teamwork, with the multidisciplinary model as most beneficial, and concentrated
hours of therapy. Negative predictors were the level of baseline severity and
disability post stroke. CLINICAL REHABILITATION IMPACT: The results indicate that
organization of services should be at target to optimize patients' outcomes in
rehabilitation. Furthermore, that concentrated hour's related to specific goals
in therapy are preferable to optimize functional recovery.
PMID- 28417612
TI - Fatigue and its relationship with physical activity in adolescents and young
adults with traumatic brain injury: a cross-sectional study.
AB - BACKGROUND: Physical activity (PA) in patients with traumatic brain injury (TBI)
may be impaired leading to secondary health issues and limitations in
participation. AIM: This study aims to determine the level of PA and its
determinants in adolescents and young adults with TBI. DESIGN: Cross-sectional
survey study. SETTING: Outpatient clinic of a rehabilitation center. POPULATION:
Discharged patients aged 12-39 years with a diagnosis of TBI >6 months treated in
the rehabilitation center between 2009-2012. METHODS: The Activity Questionnaire
for Adults and Adolescents (AQuAA) measuring PA, with results dichotomized for
meeting or not meeting Dutch recommendations for health-enhancing physical
activity (D-HEPA) and the Checklist Individual Strength questionnaire (CIS; range
20-140, higher scores represent higher levels of fatigue), measuring fatigue,
were administered. RESULTS: Fifty (47%) of the 107 invited patients completed the
questionnaire. Mean age was 25.0+/-7.2 years and 22 (44%) were male. Eighteen
(36%) had a mild injury, 13 (26%) a moderate injury and 19 (38%) a severe injury.
Median time spent on moderate-vigorous physical activity was 518 minutes/week
(IQR 236-1725) (males performing significantly more minutes on moderate-vigorous
activity than women) and on sedentary activity 2728 minutes/week (IQR 1637-3994).
Thirty-two (64%) participants met the D-HEPA. According to the CIS, 19
participants (38%) were severely fatigued. Both the CIS total score and the
subscales motivation and physical activity were associated with meeting the D
HEPA. CONCLUSIONS: The proportion of individuals with TBI meeting D-HEPA was
similar to the general population, with the PA level being associated with self
reported fatigue. CLINICAL REHABILITATION IMPACT: Physical activity programs are
continuously being developed to increase the percentage of individuals meeting
public health recommendations for PA; when developing programs for individuals
with TBI extra consideration should be taken for the presence of fatigue. As in
the general population, females with TBI are less active, PA programs should
probably consider gender differences in their development.
PMID- 28417613
TI - Combination therapy for complex peripheral artery disease: the evidence for
combining mechanical revascularization with anti-restenotic drug delivery
systems.
AB - The management of complex, lower-extremity peripheral artery disease remains a
difficult challenge, with ample room for improvement in the results seen with
current generation devices. Therapies which use a combination of multiple devices
for their mechanical and anti-restenotic properties may be advantageous, and
offer an opportunity to improve the durability of revascularization through
optimizing and individualizing care. Combination therapy typically utilizes drug
delivery devices in addition to stents and atherectomy to achieve improved
results. However, there is a paucity of high-level evidence with which to direct
treatment, with many different forms of combination therapy under investigation
and little clinical research coordination. Herein we seek to describe and
evaluate the growing number of options for combination treatment in this
challenging disease.
PMID- 28417614
TI - Spinal epidural abscess caused by Brucella species: a review of 17 cases.
AB - BACKGROUND: Spinal epidural abscess (SEA) is a rarely encountered clinical entity
during the course of Brucella infection. METHODS: We reported 17 patients
diagnosed with Brucellar SEA for a mean follow-up of 15 months. Spinal epidural
abscess was detected by magnetic resonance imaging in all cases. Brucella
diagnosis was established by serological tests. Patients were administered
antibiotics for duration of 6 to 16 weeks. RESULTS: SEA was localized in lumbar
region in 9 patients, thoracic in 4 patients, cervical in 3 patients, both
thoracic and lumbar in 1 patient. Neurologic examination was normal in 4
patients, we detected motor and/or sensory deficit in 13 patients. Symptoms
regressed in all patients after the institution of antibiotic regimens, and all
recovered fully. Surgical drainage of abscess was performed in 2 patients and 3
patients were performed limited laminectomies. CONCLUSIONS: Antibiotic therapy
could be primary treatment and is effective in required doses and duration for
many patients. If neurologic deterioration be observed despite proper antibiotic
regimens in required doses and duration, surgical intervention is to be
performed.
PMID- 28417615
TI - Granular cell tumor of the orbit: pathological features and treatment.
PMID- 28417616
TI - Cervical radiculopathy caused by vertebral artery loop.
PMID- 28417617
TI - Indocyanine green videoangiography: the thin border between a useful tool and an
illusion of safety.
PMID- 28417618
TI - Indocyanine green videoangiography application in distal (M4) middle cerebral
artery aneurysm surgery.
PMID- 28417619
TI - Human Leukocyte Antigen (HLA) Class I and II Polymorphism in Iranian Healthy
Population from Yazd Province.
AB - The major histocompatibility complex (MHC) genes are the most polymorphic loci in
the human genome and have been widely studied in various populations and ethnic
groups. Investigations into the HLA genes and proteins have been useful tool for
anthropological, transplantation and disease association studies. The
polymorphism of the HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) genes
were investigated in 90 unrelated Iranian individuals from Yazd province located
in the center of Iran using sequence-specific primers (PCR-SSP). Allele and
haplotype frequencies, expected/observed heterozygosity, unbiased expected
heterozygosity, number of effective alleles, deviations from Hardy-Weinberg (HW)
equilibrium and genetic diversity were computed. A total of 23, 48, 23, 24, 13
and 16 alleles for HLA-A, -B,-C, -DRB1, -DQA and -DQB loci were determined,
respectively in the population study. The most frequent allele identified in this
study were A*02:01 (18.889%), HLA-B* 51:01 (12.778%), HLA-C* 12:03 (17.033%), HLA
DRB* 11 (24.4%), HLA-DQA* 05:05 (20.55%) and HLA-DQB*03:01 (22.8%).Furthermore,
the most frequent 3-locus haplotypes were DRB*11-DQA*05:01-DQB*03:01 (21.1%), HLA
A*02:01- B *50:01- DRB*07:01 (4.9%) and A*26:01 -B* 38:01 -C*12:03(5%). The most
4-locus haplotype were A*11:01 -B* 52:01 -C*12:03 -DRB!*15(2.5%) and A*02:01 -B*
50:01 -DRB1*07:01 -DQB1*02:01(4.5%). The heterozygosity of the study population
was confirmed the expected value and not deviated from Hardy-Weinberg equilibrium
for all loci (p>0.05). Our study shows a close relatedness between Yazd
population and other ethnic group of Iran despite some differences, which may be
due to admixture of each one of these groups with each other or foreigner
subpopulations during centuries. Moreover, the results of this study suggest that
the Iranian population from Yazd province is in close vicinity with the
Caucasians populations and far from the Korean and Japanese populations.
PMID- 28417620
TI - Effects of Submaximal Aerobic Exercise on Regulatory T Cell Markers of Male
Patients Suffering from Ischemic Heart Disease.
AB - There are confirmed beneficiary effects of exercise on atherosclerotic
inflammation of ischemia-associated heart diseases. The purpose of this study was
to evaluate the effect of aerobic exercise on T-regulatory cell markers of IL-35
as well as FoxP3 and T-helper2 marker of IL-33 in patients with ischemic heart
disease (IHD). This research was performed on 44 asymptomatic male patients with
ischemic heart disease. The participants were randomly assigned into two groups
of submaximal aerobic exercise and control group. Blood samples were collected
before and after the termination of the exercise protocol. Serum levels of IL-35
and IL-33 as well as the amount of FoxP3 gene expression in peripheral blood
mononuclear cells were measured by Elisa and Real time PCR, respectively. Serum
levels of IL-35 (p=0.001) as well as the amount of FoxP3 gene expression
increased significantly (p=0.012) in exercise group even after controlling the
likely confounding effects of age, length of ischemia, duration of the disease,
and the amount of such factors before exercise (p<=0.042). It seems that exercise
may yield a better control of atherosclerotic inflammation in patients with
ischemic heart disease through the induction of regulatory T cells.
PMID- 28417621
TI - Inverse Relation between MxA Gene Expression and Age in Multiple Sclerosis
Patients Reveals a Gender Difference in Response to Interferon Therapy.
AB - Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease
of the central nervous system that women are at a higher risk to acquire than
men. Myxovirus resistance protein A (MxA) is used as a predictive marker of
bioactivity of interferon-beta (IFN-beta) therapy in MS patients. This study was
undertaken in west of Iran to investigate gender differences in the expression
level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-beta
therapy, compared with untreated normal individuals. The expression level of the
MxA gene in RRMS samples were compared to untreated normal individuals using the
extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and
50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15
negative and responded to IFN-beta with a normal vitamin D level. The level of
MxA gene expression was measured by quantitative RT-PCR. The levels of gene
expression were decreased in RRMS patients compared with normal counterparts
(p=0.025). This decrease was significant in females (p=0.009) compared to males
(p>0.05). The level of expression varied across different female age-groups with
no significant difference in women younger than 30 years, but a significant
decrease in expression in women between 30 to 40 years or above 40 years of age
was seen. There was neither linear correlation between the MxA expression level
and risk of expanded disability status scale of Kurtzke (EDSS); nor were there
any significant correlation between expression status of MxA and duration of the
disease. In conclusion, the decrease in the level of MxA expression in MS
patients treated with IFN-beta when compared to normal individuals was
significantly lower in females than males. This demonstrated a gender bias in
the response to IFN-beta therapy that will need to be confirmed and further
investigated in more detail.
PMID- 28417622
TI - Anti-inflammatory Effects of Novel Thiazolidinone Derivatives as Bioactive
Heterocycles on RAW264.7 Cells.
AB - The inhibition of the inducible nitric oxide synthase (iNOS), cyclooxygenase 2
(COX-2) and nuclear factor-kappaB (NF-kappaB) production are research targets of
attract in the field of anti-inflammatory drug development. Therefore, this study
was designed to investigate the anti-inflammatory effects of novel thiazolidinone
derivatives using a cellular model of lipopolysaccharide (LPS)-stimulated murine
macrophage RAW 264.7. In the present study, five new derivatives (A to E) of
thiazolidinone were synthesized and screened for anti-inflammatory activities.
Cell viability of LPS-stimulated RAW 264.7 macrophages clearly decreased in >55
MUg/mL of synthesized A-E compounds especially in the presence of C; therefore,
up to 50 MUg/mL of compounds were selected for the subsequent analysis. A
majority of these compounds showed significant inhibition on the production of NO
in LPS-stimulated macrophages in a dose-dependent manner. Compounds B and D (10
50 MUg/mL) significantly inhibited LPS-induced NF-kappaB (p65) production in a
dose-dependent manner. The effects of B and D on iNOS and COX-2 mRNA and protein
expression in LPS-stimulated RAW 264.7 cells were detected by real time-PCR and
western blot. B derivative significantly suppressed the iNOS and COX-2 mRNA level
and as well as protein expression. Taken together, these results reveal that
compound B as new thiazolidinone derivative decreased expression of the
inflammatory-related signals (NO, iNOS and COX-2) through regulation of NF
kappaB; hence, this compound could be suggested as a novel therapeutic strategy
for inflammation-associated disorders.
PMID- 28417623
TI - A Real Life Comparison between Allergenic Extracts and Allergenic Molecules.
AB - Serum IgE assay is a mainstay step in the allergy work up. Allergenic extracts
and molecular components are available at present. This real life study compared
the serum specific IgE levels against allergenic extracts with allergenic
molecules in patients allergic to Parietaria, Betulaceae, and mites. This
retrospective real life study included 489 subjects with respiratory allergy.
Inclusion criteria were 1) documented diagnosis of allergic rhinitis (AR) and/or
allergic asthma, and 2) documented allergy to Parietaria judaica (Par j) 2 (216
patients: 112 females, mean age 42 years), or to Betula verrucosa (Bet v) 1 (62
patients: 35 females, mean age 3 years), or Dermatophagoides pteronyssinus (Der
p) 1 (211 patients: 107 females, mean age 34 years); and mono-allergy. Serum IgE,
specific both for total/crude allergen extracts and individual
purified/recombinant allergens, were assessed by ImmunoCap system. The serum IgE
levels to birch extract were very strongly (R2=0.96) related to IgE to Bet v 1.
There was a strong (R2=0.71) correlation between Dermatophagoides pteronyssinus
IgE and Der p 1. A very strong (R2=0.87) correlation also existed between
Parietaria extract IgE and Par j 2 IgE levels. However, there was discrepancy
between percentages of positivity between allergenic extracts and molecules.
Therefore, allergen molecular diagnostics may represent a useful way in allergy
work up, but deserves caution in particular circumstances.
PMID- 28417624
TI - Cow's Milk Desensitization in Anaphylactic Patients: A New Personalized-dose
Method.
AB - Cow's milk allergy (CMA) is the most frequent food allergy in children and oral
immunotherapy (OIT) is a promising approach for treatment of patients. The most
challenging cases are anaphylactic with coexisting asthma and proposing safe
protocols is crucial especially in high risk groups. Considering that CMA varies
among patients, an individualized OIT protocol would be beneficial to achieve a
safer and more efficient method of desensitization. 18 children more than 3 years
of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin
prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals
had a convincing history of persistent asthma. SPT with milk extracts, whole
fresh milk and serially diluted milk concentrations were performed. The dilution
of milk that induced 3-5 mm of wheal in each individual was selected as the
starting dilution for OIT. Desensitization began by 1 drop of the defined
dilution and continued increasingly. Overall, 16 out of 18 children (88.8%)
achieved the daily intake of 120 mL of milk. Four out of these 16 children
accomplished the protocol without any adverse allergic reactions. 12 patients
experienced mild to severe reactions. Wheal and erythema in SPT (p<=0.001), and
sIgE (p<=0.003) to most milk allergens were significantly decreased following
desensitization. We successfully desensitized 16 of 18 children with IgE-mediated
CMA by individualized desensitization protocol. Individualizing the OIT protocol
would be helpful to save time and perhaps to relieve the allergic symptoms after
ingesting cow's milk intake.
PMID- 28417625
TI - Influence of Sensitization Patterns on Fractional Exhaled Nitric Oxide in
Asthmatic Children.
AB - Fractional exhaled nitric oxide (FeNO) has been suggested as a non-invasive
biomarker of airway inflammation, which is increased in atopic subjects. Whether
sensitization to particular allergens is a predictive factor for increased FeNO
levels is not yet fully understood. We conducted a retrospective cross-sectional
study. From October to December in 2015, the medical documents of 127 mild,
steroid-naive asthmatic children and 34 healthy age-matched children were
enrolled in this study. The results of the FeNO measurements, skin prick test,
and the spirometry were collected for analysis. Sensitization patterns to the 18
aeroallergens (5 categories: mites, molds, animal dander, pollen, and other) were
determined in study population. A significant increase in FeNO level was observed
in poly-sensitized asthmatic children (34.7 part per billion, (ppb) [28.3-41.1
p.p.b]), compared with mono-sensitized asthmatics (30.7 p.p.b [18.3-43.2 p.p.b])
and with non-sensitized asthmatics (17.3 p.p.b [10.8-24.5 p.p.b]). With
sensitization to perennial allergens (mites, mold, and animal dander), blood
eosinophil counts were significantly associated with increased FeNO (p<0.05 for
all). The highest FeNO level was identified in children sensitized to a
combination of the perennial, seasonal, and other allergens, when compared with
those sensitized to one category of allergen alone (p=0.004). Our study showed
that variations in FeNO level were associated with individuals' sensitization
patterns. Being sensitized to some particular allergens might contribute to
prompt the airway inflammation.
PMID- 28417626
TI - Production and Characterization of Monoclonal Antibody against Recombinant Virus
Coat Protein CP42.
AB - There are many studies related to the production of a ELISA kit for diagnosing
virus infections. However, production of most kits depends on purification of
whole virus particles, which involves the use of costly equipment and reagents.
The purpose of this study was to check out if the anti-CP42 antibodies could be
used as a diagnostic assay for detection of Grapevine fanleaf Virus (GFLV). In
this study, recombinant GFLV coat protein gene related to selected antigenic
determinants was inserted into pET-28a bacterial expression vector and the
construct (pET-28a CP42) was cloned into E. coli strain (DE3). Expressed protein
was verified with western blotting assay by the use of commercially available
anti-GFLV antibody. The recombinant protein was purified using nickel
nitrilotriacetic acid (Ni-NTA) resin. Balb/c mice were immunized with purified
protein and splenocytes of hyperimmunized mice were fused with murine myeloma
Sp2/0 cells. Positive hybridomas were selected by ELISA using CP42 as coating
antigen. The results showed that monoclonal antibody (MAb) specific to CP42 has
been successfully generated. Efficiency of produced antibody was analyzed by
ELISA and western blotting assay using some confirmed grapevine samples. The
infection was confirmed previously based on morphological features and ELISA
assay, performed using commercial anti-GFLV antibody. The monoclonal antibody
reacted with antigen in ELISA and immunoblot method. Our results demonstrated
that anti recombinant CP42 monoclonal antibodies are able to diagnose whole virus
in infected grapevine sample using ELISA test.
PMID- 28417627
TI - A Retrospective Study on the Association between Thyroid Autoantibodies with
beta2-glycoprotein and Cardiolipin Antibodies in Recurrent Miscarriage.
AB - Etiologic factors for recurrent miscarriage (RM) include autoimmune diseases, the
most frequently antiphospholipid syndrome and thyroiditis. Some women who suffer
from RM might also have an altered immune system. We aimed to evaluate possible
associations between anti-thyroid and anti-phospholipid antibodies in women with
RM. In a retrospective case series 1 on 156 women with RM, major outcome
parameters were antibodies against cardiolipin, beta2-glycoprotein I,
thyreoperoxidase (TPO-Ab), and thyroglobulin (TG-Ab). Significant (p<0.05)
positive correlations were found between TPO-Ab and TG-Ab (r=0.577), TPO-Ab and
IgG anti-cardiolipin antibodies (r=0.284), TPO-Ab and IgG anti- beta2
glycoprotein I antibodies (r=0.196), and TG-Ab and IgG anti-cardiolipin
antibodies (r=0.193), as well as between all types of anti-phospholipid
antibodies. Women with both increased TPO-Ab and TG-Ab levels revealed higher
(p<0.001) IgG anti-cardiolipin and IgG anti-beta2-glycoprotein I antibodies. Anti
thyroid antibodies were linked to anti-phospholipid antibodies and should be in
the focus of future research on RM.
PMID- 28417629
TI - Symptom Severity and Allergen-specific IgE in Allergic Rhinitis.
AB - No Abstract##.
PMID- 28417628
TI - Role of Gut Microbiota and Infectious Burden in the Development of Autoimmune and
Allergic Diseases.
AB - No Abstract#.
PMID- 28417630
TI - Self-Healable and Reprocessable Polysulfide Sealants Prepared from Liquid
Polysulfide Oligomer and Epoxy Resin.
AB - Polysulfide sealants have been commercially applied in many industrial fields. In
this article, we study the self-healing property of the epoxy resin-cured
polysulfide sealants for the first time. The obtained sealants showed a flexible
range of ultimate elongation of 157-478% and a tensile strength of 1.02-0.75 MPa
corresponding to different polysulfide oligomers. By taking advantage of the
dynamic reversible exchange of disulfide bonds, polysulfide sealants exhibited
good self-healing ability under a moderate thermal stimulus. A higher molecular
weight and a lower degree of cross-linking of polysulfide oligomer were helpful
in improving the ultimate elongation and healing efficiency of the polysulfide
sealants. After subjecting to a temperature of 75 degrees C for 60 min, both the
tensile strength and ultimate elongation of a fully cut sample, LP55-F, were
restored to 91% of the original values, without affecting the sealing property.
Furthermore, the sample exhibited excellent reshaping and reprocessing abilities.
These outcomes offer a paradigm toward sustainable industrial applications of the
polysulfide-based sealants.
PMID- 28417631
TI - Inkjet-Printed Quantum Dot Light-Emitting Diodes with an Air-Stable Hole
Transport Material.
AB - High-efficiency quantum dot light-emitting diodes (QLEDs) were fabricated using
inkjet printing with a novel cross-linkable hole transport material N,N'-(9,9'
spirobi[fluorene]-2,7-diylbis[4,1-phenylene])bis(N-phenyl-4'-vinyl-[1,1'
biphenyl]-4-amine) (SDTF). The cross-linked SDTF film has excellent solvent
resistance, high thermal stability, and the highest occupied molecular orbital
(HOMO) level of -5.54 eV. The inkjet-printed SDTF film is very smooth and
uniform, with roughness as low as 0.37 nm, which is comparable with that of the
spin-coated film (0.28 nm). The SDTF films stayed stable without any pinhole or
grain even after 2 months in air. All-solution-processed QLEDs were fabricated;
the maximum external quantum efficiency of 5.54% was achieved with the inkjet
printed SDTF in air, which is comparable to that of the spin-coated SDTF in a
glove box (5.33%). Electrical stabilities of both spin-coated and inkjet-printed
SDTF at the device level were also investigated and both showed a similar
lifetime. The study demonstrated that SDTF is very promising as a printable hole
transport material for making QLEDs using inkjet printing.
PMID- 28417632
TI - Evidence of Multiple Sorption Modes in Layered Double Hydroxides Using Mo As
Structural Probe.
AB - Layered double hydroxides (LDHs) have been considered as effective phases for the
remediation of aquatic environments, to remove anionic contaminants mainly
through anion exchange mechanisms. Here, a combination of batch isotherm
experiments and X-ray techniques was used to examine molybdate (MoO42-) sorption
mechanisms on CaAl LDHs with increasing loadings of molybdate. Advanced modeling
of aqueous data shows that the sorption isotherm can be interpreted by three
retention mechanisms, including two types of edge sites complexes, interlayer
anion exchange, and CaMoO4 precipitation. Meanwhile, Mo geometry evolves from
tetrahedral to octahedral on the edge, and back to tetrahedral coordination at
higher Mo loadings, indicated by Mo K-edge X-ray absorption spectra. Moreover, an
anion exchange process on both CaAl LDHs was followed by in situ time-resolved
synchrotron-based X-ray diffraction, remarkably agreeing with the sorption
isotherm. This detailed molecular view shows that different uptake mechanisms
edge sorption, interfacial dissolution-reprecipitation-are at play and control
anion uptake under environmentally relevant conditions, which is contrast to the
classical view of anion exchange as the primary retention mechanism. This work
puts all these mechanisms in perspective, offering a new insight into the complex
interplay of anion uptake mechanisms by LDH phases, by using changes in Mo
geometry as powerful molecular-scale probe.
PMID- 28417633
TI - pH-Responsive Graphene Oxide-DNA Nanosystem for Live Cell Imaging and Detection.
AB - The interaction between graphene oxide (GO) and DNA is very sensitive to the
environment. For example, under acidic conditions, the affinity of GO for DNA is
enhanced, weakening the capability of GO to distinguish DNAs with different
conformations. This effect has impeded the development of sensitive pH biosensors
based on GO-DNA nanosystems. In this work, we systematically studied the affinity
between GO and i-motif forming oligonucleotides (IFOs) at different pH values and
developed a herring sperm DNA (HSD) treatment method. Using this method, HSD
occupies the surface of GO, compromising the attractive force of GO that is
significantly enhanced under acidic conditions. As a result, the ability of GO to
distinguish between "open" and "closed" IFOs is successfully generalized to a
wider pH range. Finally, a pH-sensitive GO-IFO nanosystem was fabricated that
showed excellent sensing ability both in vitro and for intracellular pH
detection. Because the interaction between GO and DNA is the basis for
constructing GO-DNA biosensors, the strategy developed in this work shows great
potential to be applied in a variety of other GO-DNA sensing systems.
PMID- 28417634
TI - Anti-influenza A Virus Activity of Dendrobine and Its Mechanism of Action.
AB - Dendrobine, a major component of Dendrobium nobile, increasingly draws attention
for its wide applications in health care. Here we explore potential effects of
dendrobine against influenza A virus and elucidate the underlying mechanism. Our
results indicated that dendrobine possessed antiviral activity against influenza
A viruses, including A/FM-1/1/47 (H1N1), A/Puerto Rico/8/34 H274Y (H1N1), and
A/Aichi/2/68 (H3N2) with IC50 values of 3.39 +/- 0.32, 2.16 +/- 0.91, 5.32 +/-
1.68 MUg/mL, respectively. Mechanism studies revealed that dendrobine inhibited
early steps in the viral replication cycle. Notably, dendrobine could bind to the
highly conserved region of viral nucleoprotein (NP), subsequently restraining
nuclear export of viral NP and its oligomerization. In conclusion, dendrobine
shows potential to be developed as a promising agent to treat influenza virus
infection. More importantly, the results provide invaluable information for the
full application of the Traditional Chinese Medicine named "Shi Hu".
PMID- 28417635
TI - Crystallization of Amphiphilic DNA C-Stars.
AB - Many emerging technologies require materials with well-defined three-dimensional
nanoscale architectures. Production of these structures is currently underpinned
by self-assembling amphiphilic macromolecules or engineered all-DNA building
blocks. Both of these approaches produce restricted ranges of crystal geometries
due to synthetic amphiphiles' simple shape and limited specificity, or the
technical difficulties in designing space-filling DNA motifs with targeted
shapes. We have overcome these limitations with amphiphilic DNA nanostructures,
or "C-Stars", that combine the design freedom and facile functionalization of DNA
based materials with robust hydrophobic interactions. C-Stars self-assemble into
single crystals exceeding 40 MUm in size with lattice parameters exceeding 20 nm.
PMID- 28417636
TI - Semifluorinated Synergistic Nonfouling/Fouling-Release Surface.
AB - The preparation of a fluorine-containing synergistic nonfouling/fouling-release
surface, using a b-PFMA-PEO asymmetric molecular brush possessing both
poly(ethylene glycol) (PEO) and poly(2,2,2-trifluoroethyl methacrylate) (PFMA)
side chains densely distributed on the same repeat unit along the polymeric
backbone, is reported. On the basis of the poly(Br-acrylate-alkyne) macroagent
comprising two functionalities (alkynyl and 2-bromopropionate), which is prepared
by reversible addition-fragmentation chain transfer homopolymerization of a new
trifunctional acrylate monomer of Br-acrylate-alkyne, b-PFMA-PEO asymmetric
molecular brushes are obtained by concurrent atom transfer radical polymerization
and Cu-catalyzed azide/alkyne cycloaddition "click" reaction in a one-shot
system. A spin-cast thin film of the b-PFMA-PEO asymmetric molecular brush
exhibits a synergistic antifouling property, in which PEO side chains endow the
surface with a nonfouling characteristic, whereas PFMA side chains display the
fouling-release functionality because of their low surface energy. Both protein
adsorption and cell adhesion tests provided estimates of the antifouling activity
of the asymmetric molecular brush surfaces, which was demonstrated to be
influenced by the degree of polymerization of the backbone and the length of the
PEO and PFMA side chains. With compositional heterogeneities, all asymmetric
molecular brush surfaces show considerable antifouling performance with much less
protein adsorption (at least 45% off, up to 75% off) and cell adhesion (at least
70% off, up to 90% off) in comparison with a bare surface.
PMID- 28417637
TI - Synergistic Enhancement of Microwave Absorption Using Hybridized
Polyaniline@helical CNTs with Dual Chirality.
AB - In this study, we designed a dual-chirality hierarchical structure to achieve a
synergistically enhanced effect in microwave absorption via the hybridization of
nanomaterials. Herein, polyaniline (PANi) nanorods with tunable chirality are
grown on helical carbon nanotubes (HCNTs), a typical nanoscale chiral structure,
through in situ polymerization. The experimental results show that the
hierarchical hybrids (PANi@HCNTs) exhibit distinctly dual chirality and a
significant enhancement in electromagnetic (EM) losses compared to those of
either pure PANi or HCNTs. The maximum reflection loss of the as-prepared hybrids
can reach -32.5 dB at 8.9 GHz. Further analysis demonstrates that combinations of
chiral acid-doped PANi and coiled HCNTs with molecular and nanoscale chirality
lead to synergistic effects resulting from the dual chirality. The so-called
cross-polarization may result in additional interactions with induced EM waves in
addition to multiscaled relaxations from functional groups and interfacial
polarizations, which can benefit EM absorption.
PMID- 28417638
TI - Mimicking Complex Biological Membranes and Their Programmable Glycan Ligands with
Dendrimersomes and Glycodendrimersomes.
AB - Synthetic vesicles have been assembled and coassembled from phospholipids, their
modified versions, and other single amphiphiles into liposomes, and from block
copolymers into polymersomes. Their time-consuming synthesis and preparation as
stable, monodisperse, and biocompatible liposomes and polymersomes called for the
elaboration of new synthetic methodologies. Amphiphilic Janus dendrimers (JDs)
and glycodendrimers (JGDs) represent the most recent self-assembling amphiphiles
capable of forming monodisperse, stable, and multifunctional unilamellar and
multilamellar onion-like vesicles denoted dendrimersomes (DSs) and
glycodendrimersomes (GDSs), dendrimercubosomes (DCs), glycodendrimercubosomes
(GDCs), and other complex architectures. Amphiphilic JDs consist of hydrophobic
dendrons connected to hydrophilic dendrons and can be thought of as monodisperse
oligomers of a single amphiphile. They can be functionalized with a variety of
molecules such as dyes, and, in the case of JGDs, with carbohydrates. Their
iterative modular synthesis provides efficient access to sequence control at the
molecular level, resulting in topologies with specific epitope sequence and
density. DSs, GDSs, and other architectures from JDs and JGDs serve as powerful
tools for mimicking biological membranes and for biomedical applications such as
targeted drug and gene delivery and theranostics. This Review covers all aspects
of the synthesis of JDs and JGDs and their biological activity and applications
after assembly in aqueous media.
PMID- 28417639
TI - A Simple Descriptor to Rapidly Screen CO Oxidation Activity on Rare-Earth Metal
Doped CeO2: From Experiment to First-Principles.
AB - Ceria (CeO2) is an attractive catalyst because of its unique properties, such as
facile redoxability and high stability. Thus, many researchers have examined a
wide range of catalytic reactions on ceria nanoparticles (NPs). Among those
contributions are the reports of the dopant-dependent catalytic activity of
ceria. On the other hand, there have been few mechanistic studies of the effects
of a range of dopants on the chemical reactivity of ceria NPs. In this study, we
examined the catalytic activities of pure and Pr, Nd, and Sm-doped CeO2 (PDC,
NDC, and SDC, respectively) NPs on carbon monoxide (CO) oxidation. Density
functional theory (DFT) calculations were also performed to elucidate the
reaction mechanism on rare-earth (RE)-doped CeO2(111). The experimental results
showed that the catalytic activities of CO oxidation were in the order of CeO2 >
PDC > NDC > SDC. This is consistent with the DFT results, where the reaction is
explained by the Mars-van Krevelen mechanism. On the basis of the theoretical
interpretation of the experimental results, the ionic radius of the RE dopant can
be used as a simple descriptor to predict the energy barrier at the rate
determining step, thereby predicting the entire reaction activity. Using the
descriptor, a wide range of RE dopants on CeO2(111) were screened for CO
oxidation. These results provide useful insights to unravel the CO oxidation
activity on various oxide catalysts.
PMID- 28417641
TI - Editorial for AVCC relaunch issue.
PMID- 28417640
TI - Combinations of L-NG-monomethyl-arginine and oseltamivir against pandemic
influenza A virus infections in mice.
AB - L-NG-monomethyl-arginine (L-NMMA) is an experimental compound that suppresses
nitric oxide production in animals. The compound was combined with oseltamivir to
treat lethal influenza A/California/04/2009 (H1N1) pandemic virus infections in
mice. Treatments were given twice a day for five days starting 4 h (oseltamivir,
by oral gavage) or three days (L-NMMA, by intraperitoneal route; corresponding to
the time previously reported for nitric oxide induction in the animals) after
infection. Low doses of oseltamivir were used in order to demonstrate synergy or
antagonism. Oseltamivir monotherapy protected 70% of mice from death at 1
mg/kg/day. L-NMMA (40 and 80 mg/kg/day) was ineffective alone in preventing
mortality. Compared to oseltamivir treatment alone, L-NMMA combined with
oseltamivir was synergistically effective (as evaluated by three-dimensional
MacSynergy analysis), resulting in survival increases from 20 to 70% when 40 or
80 mg/kg/day of L-NMMA was combined with 0.3 mg/kg/day of oseltamivir, and from
70 to 100% survival increases when these doses were combined with 1 mg/kg/day of
oseltamivir. These data demonstrate that a nitric oxide inhibitor such as L-NMMA
has the potential to be beneficial when combined with oseltamivir in treating
influenza virus infections.
PMID- 28417642
TI - Equilibrative nucleoside transporter 1 expression in primary human hepatocytes is
highly variable and determines uptake of ribavirin.
AB - Aims Ribavirin is a nucleoside analogue and remains a necessary component of both
interferon-based and directly acting anti-viral regimens for the treatment of
hepatitis C virus infection. The achievable concentration of ribavirin within
hepatocytes is likely to be an important determinant of therapeutic outcome. In
vitro expression levels of equilibrative nucleoside transporter 1 (ENT1) has been
shown to be a predictor of treatment response in patients receiving nucleoside
based chemotherapeutic agents. We therefore investigated whether a similar
relationship existed between ENT1 expression and ribavirin uptake in freshly
isolated primary hepatocytes. Methods Primary hepatocytes were cultured on
collagen-coated plates and exposed to ribavirin. Parallel samples were taken for
high-performance liquid chromatography to assess ribavirin uptake and for
quantitative polymerase chain reaction to evaluate ENT1 expression. Similar
assays were performed on the human hepatoma cell line (Huh7). ENT1 gene sequence
was analysed by cloning of polymerase chain reaction amplified complementary DNA
followed by direct sequencing. Results There was a strong direct correlation
between expression of ENT1 in primary hepatocytes and ribavirin uptake at 24 hr.
Huh7 cells expressed ENT1 at similar levels to the majority of primary
hepatocytes, but did not take up ribavirin. Sequencing revealed that ENT1 in Huh7
cells is wild type. Conclusions In this study, we clearly demonstrate that
ribavirin uptake in primary human hepatocytes is variable and correlates with
ENT1 expression. This variation in ENT1 expression may account for differences in
response rate in patients receiving ribavirin-based anti-hepatitis C virus
therapy.
PMID- 28417643
TI - Feeling bad about progress does not lead people want to change their health
behaviour.
AB - OBJECTIVE: When do people decide to do something about problematic health
behaviours? Theoretical models and pragmatic considerations suggest that people
should take action when they feel bad about their progress - in other words, when
they experience negative progress-related affect. However, the impact of progress
related affect on goal striving has rarely been investigated. DESIGN AND METHODS:
Study 1 (N = 744) adopted a cross-sectional design and examined the extent to
which measures of progress-related affect were correlated with intentions to take
action. Study 2 (N = 409) investigated the impact of manipulating progress
related affect on intentions and behaviour in an experimental design. RESULTS:
Study 1 found that, while engaging in health behaviours had the expected
affective consequences (e.g. people felt bad when they were not eating healthily,
exercising regularly or limiting their alcohol consumption), it was feeling good
rather than bad about progress that was associated with stronger intentions.
Study 2 replicated these findings. Participants induced to feel good about their
eating behaviour had marginally stronger intentions to eat healthily than
participants led to feel bad about their eating behaviour. CONCLUSION: The
findings have implications for interventions designed to promote changes in
health behaviour, as well as theoretical frameworks for understanding self
regulation.
PMID- 28417644
TI - Does Social Interaction Matter Psychological Well-Being in Persons With Dementia?
AB - BACKGROUND: Social interaction between residents and staff is an important factor
influencing sense of well-being. This study examined the relationship between
staff-resident interactions and psychological well-being of persons with
dementia. METHODS: A total of 831 observations of 110 persons with dementia in 17
nursing homes and 6 assisted living facilities were included. Psychological well
being was measured by observed displays of positive and negative emotional
expressions. Social interaction was determined by the type of social interaction
(ie, verbal interaction, nonverbal interaction, and both verbal and nonverbal
interactions) and the quality of interaction (ie, positive, negative, and
neutral). RESULTS: Verbal or both verbal and nonverbal interactions showed
significant relationship with positive and negative emotional expressions.
Positive interaction was significantly associated with more positive emotional
expression, whereas negative interaction was not. CONCLUSION: Staff-resident
interactions are important to promote the psychological well-being of persons
with dementia in residential care.
PMID- 28417645
TI - The early chain of care and risk of death in acute stroke in relation to the
priority given at the dispatch centre: A multicentre observational study.
AB - BACKGROUND: The early chain of care is critical for stroke patients. The most
important part is the so-called 'system delay' i.e. the delay time from call to
the emergency medical services until a diagnosis is established (computer
tomography). AIM: The purpose of this study was to relate the initial priority
level given by the dispatch centre to the early chain of care in acute stroke and
to short-term and long-term mortality. METHODS: All patients hospitalised with
the first and the final diagnosis of acute stroke, 15 December 2010-15 April
2011, were recruited across nine hospitals, each hospital with a stroke care
unit. RESULTS: In all, 897 stroke patients were included. Priority at the
dispatch centre: 54% received highest priority 1, 41% priority 2 and 5% priority
3. Median system delay from call to emergency medical services until diagnosis by
computer tomography was 2 h and 52 min, 4 h and 49 min and 6 h and 33 min
respectively in the three priority groups ( p<0.0001). There was a similarly
strong association between priority level at the dispatch centre and system delay
to arrival in a hospital ward, suspicion of stroke by the emergency medical
services nurse as well as the physician on hospital admission and the proportion
of patients given thrombolysis. Mortality during the subsequent 30 days was 22%
among patients with priority 1 and 14% among patients with priority 2.
CONCLUSION: Patients given a lower priority level at the dispatch centre had the
longest system delay. Although many of these patients died, the risk of death was
highest among those given the highest priority.
PMID- 28417646
TI - Cerebral hemodynamic assessment and neuroimaging across the lifespan in sickle
cell disease.
AB - Children and adults with sickle cell anemia (SCA) have a higher risk of strokes
compared to age- and race-matched peers. Velocity in the middle cerebral or
distal internal carotid artery as measured by transcranial Doppler ultrasound is
a recognized method to identify children but not adults with SCA at high-risk for
first stroke. For both children and adults with SCA that have had a stroke, no
methods clearly identify individuals at highest risk of recurrent strokes or an
initial silent stroke, the most common neurological injury. Methods to assess
cerebral hemodynamics in SCA have been utilized for decades but often required
radiotracers making them not feasible for screening and longitudinal follow-up.
MRI approaches that do not require exogenous contrast have been introduced and
are appealing in both clinical and research scenarios. Improved neuroimaging
strategies hold promise for identifying individuals with SCA at increased risk of
initial and recurrent infarcts, justifying more aggressive risk-based therapy. We
review the epidemiology of stroke in SCA, the impact of strokes, stroke
mechanisms, and potential imaging strategies including regional and global oxygen
extraction fraction, cerebral blood flow, and vessel wall imaging to identify
individuals at high-risk of stroke.
PMID- 28417647
TI - Mixed states in bipolar disorder - changes in DSM-5 and current treatment
recommendations.
AB - OBJECTIVE: Mixed states in affective disorders represent a particular challenge
in clinical routine, characterized by a complicated course of treatment and a
worse treatment response. METHODS: Clinical features of mixed states and the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are
presented and critical discussed. We then performed a systematic review using the
terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options.
RESULTS: For pharmacological treatment of mixed states in total, there is still
insufficient data from RCTs. However, there is some evidence for efficacy in
mixed states from RCTs for atypical antipsychotics, especially olanzapine,
aripiprazole and asenapine as well as mood stabilizers as valproate and
carbamazepine. CONCLUSIONS: Mixed states are of a high clinical relevance and the
DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages
of a better characterization of patients with former DSM-IV-defined mixed
episodes, disadvantages arise for example differential diagnoses with a
substantial overlap in symptoms such as borderline personality disorders.
Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a
limited sample of RCTs. LIMITATIONS: The number of RCTs in the treatment of mixed
states is highly limited. Furthermore, nearly all studies were funded by
pharmaceutical companies which may lead to an underestimation of classical mood
stabilizers such as lithium.
PMID- 28417648
TI - Danish translation and validation of Kessler's 10-item psychological distress
scale - K10.
AB - BACKGROUND: Psychological distress is a trans-diagnostic feature of mental
suffering closely associated with mental disorders. Kessler's 10-item
Psychological Distress Scale (K10), a scale with sound psychometric properties,
is widely used in epidemiological studies. AIM: To translate and investigate
whether K10 is a reliable and valid rating scale for the measurement of
psychological distress in a Danish population. METHODS: The translation was
carried out according to official WHO translation guidelines. A sample of 100
subjects was included, 54 patients from the regional Mental Health Service (MHS)
and 46 subjects with no psychiatric history. All participants were assessed with
a psychiatric diagnostic interview (MINI) and handed out K10. Concurrent validity
was assessed by WHO Well-being Index (WHO-5). Correlation matrix analysis was
conducted for the full sample and receiver operating characteristic (ROC) curves
for discriminating mental health service affiliation. RESULTS: Mean K10 scores
differed, with decreasing levels, between inpatients and outpatient in MHS and
the subjects with no psychiatric history. Factor analysis confirmed a
unidimensional structure, and Cronbach's alpha and Omega showed excellent
internal reliability. AUC for the K10 ROC curves showed excellent sensitivity
(0.947 [0.900-0.995]), accurately differentiating mental health from non-mental
health patients. CONCLUSION: The Danish K10 has the same strong internal
reliability as the original English version, and scores differ between
psychiatric patients in outpatient and emergency ward settings. CLINICAL
IMPLICATIONS: The Danish K10 translation is authorized and freely available for
download at https://www.hcp.med.harvard.edu/ncs/k6_scales.php . The utility as an
instrument for clinical screening in a mental healthcare setting is supported.
PMID- 28417649
TI - Internal dysregulation of the renin system in patients with stable liver
cirrhosis.
AB - Sodium retention in cirrhosis is associated with changes in the renin-angiotensin
aldosterone system (RAAS), the sympathetic nervous system (SNS), and the
glomerular filtration rate (GFR). We hypothesized that in cirrhosis the acute
reactions of RAAS and SNS to volume expansion are qualitatively intact, but
occurring from elevated baseline levels. Acute cardiovascular, neurohumoral and
renal responses to central blood volume changes were studied in cirrhotic
patients and healthy controls. In patients, baseline plasma renin concentration
(PRC) was elevated 5-fold compared to controls (p < .001); it increased during
standing (+144%, p < .001) and remained elevated during subsequent sitting
(+118%, p < .001). At baseline, plasma angiotensin II (pANGII) was not elevated
significantly (14 +/- 2 vs. 9 +/- 2 pg/mL) in contrast to plasma aldosterone
(pAldo, +160%, p < .001). During orthostatic RAAS activation, the rise in pAngII
per unit increase in PRC was 0.04 pg AngII/mIU and 0.48 pg AngII/mIU in patients
and controls, respectively (p < .001); similarly, the change in pAldo per unit
change in pANGII was 3.6 in patients and 14.5 pg/pg in controls (p < .001).
Plasma noradrenaline was elevated in the patients, but the dynamic changes were
virtually identical to those of controls. During standing, abrupt decreases in
renal blood flow (-63%, p < .001) and GFR (-42% p < .04) occurred only in
patients. In conclusion, in stable cirrhosis, static and dynamic dysregulation
exists within the RAAS; in the supine position pAngII levels are inappropriately
low, and the AngII-mediated regulation of aldosterone secretion is severely
impeded. In cirrhotic patients, profound reductions in renal blood flow and GFR
occur during standing.
PMID- 28417650
TI - Assessment potential of a new suture simulator in laparoscopic surgical skills
training.
AB - BACKGROUND: The skills necessary for performing effective laparoscopic suturing
are difficult to acquire; as a result, simulators for learning these skills are
rapidly becoming integrated into surgical training. The aim of the study was to
verify whether a new hybrid simulator has the potential to measure skill
improvement in young, less experienced gastroenterological surgeons. MATERIAL AND
METHODS: The study included 12 surgeons (median age, 29 (27-38)] years; 11 men
(91.7%), one woman (8.3%)) who participated in a two-day laparoscopic training
seminar. We used the new simulator before and after the program to evaluate
individual performance. Skills were evaluated using five criteria: volume of air
pressure leakage, number of full-thickness sutures, suture tension, wound area,
and performance time. RESULTS: Air pressure leakage was significantly higher
after than before the training (p = .027). The number of full-thickness sutures
was significantly higher post-training (p < .01). Suture tension was
significantly less post-training (p = .011). Wound opening areas were
significantly smaller post-training (p = .018). Performance time was
significantly shorter post-training (p = .032). CONCLUSIONS: Our study
demonstrated the assessment quality of this new laparoscopic suture simulator.
PMID- 28417651
TI - Laparoscopic management of cholecystoenteric fistula: A single-center experience.
AB - Aim To report our experience regarding management of cholecystoenteric fistula
(CEF) and identify the most effective diagnostic methods and surgical treatment.
Methods In total, 10,588 patients underwent laparoscopic cholecystectomy for
cholecystolithiasis from January 2000 to December 2014 at the Research Institute
of General Surgery, Jinling Hospital (Nanjing, China). Twenty-nine patients were
diagnosed with CEF preoperatively or intraoperatively. Data were retrospectively
collected on demographics, preoperative diagnostics, intraoperative findings,
laparoscopic procedures, complications, and follow-up. Results Twenty-nine
patients (female/male ratio, 2.2; mean age, 68.7 years) with CEF were evaluated.
Twenty-three (79.3%) patients had a cholecystoduodenal fistula (CDF), four
(13.8%) had a cholecystocolonic fistula (CCF), one (3.4%) had a cholecystogastric
fistula, and one (3.4%) had a CDF combined with a CCF. Only nine (31.0%) patients
obtained a preoperative diagnosis. All patients initially underwent laparoscopic
treatment, but five (17.2%) underwent conversion to open surgery; three of these
five developed postoperative morbidity or mortality, and the other two had an
uneventful postoperative course. Among patients managed successfully by
laparoscopy, the hospital stay ranged from 3 to 6 days (mean, 4 days). All
patients were asymptomatic at a mean follow-up of 13 months (range, 3-21 months).
Conclusion Ultrasound and computed tomography can provide valuable diagnostic
clues for CEF. Laparoscopic management of CEF in experienced hands is safe,
feasible, and associated with rapid postoperative recovery.
PMID- 28417652
TI - Modified laparoscopic cholecystectomy technique for treatment of situs inversus
totalis: A case report.
AB - Laparoscopic cholecystectomy is a broadly used technique for gallbladder
treatment. However, situs inversus, a rare anomaly, is reportedly difficult to
treat by conventional laparoscopic cholecystectomy. A 36-year-old woman with
chronic cholecystitis and multiple gallstones was found to have dextrocardia on a
chest X-ray. Magnetic resonance imaging demonstrated situs inversus,
cholecystitis, and cholelithiasis. We successfully performed laparoscopic
cholecystectomy using our modified technique, which mainly involved a left-handed
operation and adjustment of the port positions. This case will be very
instructive for right-handed surgeons in the management of cholelithiasis by
laparoscopic cholecystectomy in patients with situs inversus.
PMID- 28417653
TI - Modified Dufourmentel flap with superior pedicle: a useful technique for
sacrococcygeal pilonidal sinus.
AB - PURPOSE: In order to prevent postoperative infection and recurrence of
sacrococcygeal pilonidal sinus, the authors developed a modified Dufourmentel
flap, involving the superior pedicles, and designed a descriptive prospective
study to evaluate its efficiency. METHODS: Between July 2007 and March 2014, 16
patients with sacrococcygeal pilonidal sinus were treated with an irregular
quadrilateral excision and reconstruction by a modified Dufourmentel flap with
superior pedicle. The duration of wound healing, presence of wound complications
and permanent hypoesthesia, and recurrence rates were recorded and assessed.
RESULTS: None of the patients developed flap necrosis or wound infection
postoperatively. The duration of wound healing was 7.2 +/- 2.9 (range = 6-15)
days. Wound dehiscence was demonstrated in only one patient (6.3%). The mean
follow-up period was 4 years and 2 months (range = 4 months-8 years and 8
months), whereby no permanent hypoesthesia or recurrence was detected.
CONCLUSION: The modified Dufourmentel flap with superior pedicle can be safely
used as a treatment of sacrococcygeal pilonidal sinus, with excellent results.
PMID- 28417654
TI - Assessment of burn size in obese adults; a literature review.
AB - PURPOSE: Obesity causes changes in the total body surface area as well as the
distribution of skin surfaces. In burn management, three methods are commonly
used to determine the surface area burned: the patient's palm, the rule of nines,
and the Lund-Browder chart. These methods rely on the distribution of skin
surface, although none of these methods consider differences in body mass. This
study investigates the relationship between body surfaces and body mass in the
assessment of burn size to determine the validity of the conventional methods
when applied to obese individuals. METHODS: The current literature was reviewed
using relevant electronic databases. The initial search yielded 247 results.
Relevant articles were then reviewed. A total of seven publications fulfilled the
inclusion criteria. RESULTS: The palmar surface area ranged between 0.59%-1.22%,
depending on BMI, gender, and ethnicity, compared to 1% according to conventional
methods. The palmar surface area of obese individuals approximated 0.7% of the
total body surface area in Caucasians. The surface areas comprised 5%-7.5% of the
total body surface area for each arm, 15%-20% for each leg, and 40%-52% for the
trunk in obese or morbidly obese individuals, compared to 9%, 18%, and 36%,
respectively, for normal-weight adults. CONCLUSIONS: The commonly used methods
for assessment of burns should be used with caution when applied to obese burn
patients, and the clinical parameters observed even more systematically.
PMID- 28417655
TI - Dimensionality of the Chinese hospital anxiety depression scale in psychiatric
outpatients: Mokken scale and factor analyses.
AB - OBJECTIVE: The hospital anxiety and depression scale (HADS) is a widely used
scale of anxiety and depression. However, recent studies have challenged the bi
dimensional scoring of the HADS. The present study was to examine the
dimensionality of the Chinese HADS. METHODS: We recruited a convenience sample of
214 adult psychiatric outpatients at a medical centre in Taiwan, and they
completed the Chinese HADS. We used Mokken scale analysis (MSA), exploratory
factor analysis (EFA), exploratory bifactor analysis (EBA) and confirmatory
factor analysis (CFA) to examine the dimensionality of the Chinese HADS. RESULTS:
The Chinese HADS was a moderate Mokken scale (Hs = 0.44), and had a two-factor
structure. EBA showed that one general factor, emotional distress, explained 68%
of the common variance of the Chinese HADS. CFA confirmed that the bifactor model
had the best fit statistics. The items 5 and 7 of the Chinese HADS contributed to
structural ambiguity in the Chinese HADS subscales. CONCLUSIONS: The sum scores
of the Chinese HADS were a reliable and valid unidimensional measure of emotional
distress. The Chinese HADS subscales were incapable of differentiating between
anxiety and depression. Clinicians and researchers should choose other scales
that are specifically designed for measuring anxiety and depression.
PMID- 28417656
TI - In-vivo imaging of meningeal inflammation in multiple sclerosis: Presence of
evidence or evidence of presence?
PMID- 28417657
TI - A "kissing lesion": In-vivo 7T evidence of meningeal inflammation in early
multiple sclerosis.
AB - BACKGROUND: The role of cortical lesions (CLs) in disease progression and
clinical deficits is increasingly recognized in multiple sclerosis (MS); however
the origin of CLs in MS still remains unclear. OBJECTIVE: Here, we report a para
sulcal CL detected two years after diagnosis in a relapsing-remitting MS (RRMS)
patient without manifestation of clinical deficit. METHODS: Ultra-high field (7T)
MR imaging using magnetization-prepared 2 rapid acquisition gradient echoes
(MP2RAGE) sequence was performed. RESULTS: A para-sulcal CL was detected which
showed hypointense rim and iso- to hyperintense core. This was detected in the
proximity of the leptomeninges in the left precentral gyrus extending to the
adjacent postcentral gyrus. CONCLUSION: This finding indicates that inflammatory
infiltration into the cortex through the meninges underlies cortical pathology
already in the early stage of disease and in mild disease course.
PMID- 28417658
TI - Resident Involvement in Professional Otolaryngology Organizations: Current Trends
in the United States.
AB - Involvement by residents in professional medical organizations can enrich their
training, but little data exist regarding the number and types of involvement
opportunities available to otolaryngology residents. We sought to fill this gap
in knowledge by quantifying the extent to which major otolaryngology-related
organizations in the United States provide involvement opportunities to
otolaryngology residents. Our analysis included 23 organizations and subspecialty
societies. Results showed that many opportunities exist for residents to attend
conferences and present research; however, fewer involvement and funding
opportunities existed in any other leadership, health policy, or service-learning
experiences. These findings were consistent across general and subspecialty
societies. Given the many purported benefits of resident involvement in
otolaryngology outside of the standard training environment, future efforts may
be warranted to increase the number and type of involvement opportunities
currently available in professional societies.
PMID- 28417659
TI - Effects of [Nphe1, Arg14, Lys15] N/OFQ-NH2 (UFP-101), a potent NOP receptor
antagonist, on molecular, cellular and behavioural alterations associated with
chronic mild stress.
AB - The present study investigated the effect of [Nphe1] Arg14, Lys15-N/OFQ-NH2 (UFP
101), a selective NOP receptor antagonist, in chronic mild stress (CMS) in male
Wistar rats. NOP receptor antagonists were reported to elicit antidepressant-like
effects in rodents. Our aim was to investigate UFP-101 effects on CMS-induced
anhedonia and impairment of hippocampal neurogenesis. UFP-101 (10 nmol/rat
intracerebroventricularly) did not influence sucrose intake in non-stressed
animals, but reinstated basal sucrose consumption in stressed animals from the
second week of treatment. UFP-101 also reversed stress effects in forced swimming
test and in open field. Fluoxetine (10 mg/kg intraperitoneally) produced similar
effects. Moreover, we investigated whether UFP-101 could affect CMS-induced
impairment in hippocampal cell proliferation and neurogenesis, and in fibroblast
growth factor (FGF-2) expression. Our data confirm that CMS reduced neural stem
cell proliferation and neurogenesis in adult rat hippocampus. Chronic UFP-101
treatment did not affect the reduced proliferation (bromodeoxyuridine-positive
cells) observed in stressed animals. However, UFP-101 increased the number of
doublecortin-positive cells, restoring neurogenesis. Finally, UFP-101
significantly increased FGF-2 expression, reduced by CMS. These findings support
the view that blockade of NOP receptors produces antidepressant-like effects in
CMS associated with positive effects on neurogenesis and FGF-2 expression.
Therefore, NOP receptors may represent a target for innovative antidepressant
drugs.
PMID- 28417660
TI - Anatomic Characteristics, Identification, and Protection of the Nonrecurrent
Laryngeal Nerve during Thyroidectomy.
AB - Objective We aimed to investigate the anatomical features and variation pattern
of the nonrecurrent laryngeal nerve (NRLN), summarize the methods for identifying
the NRLN before and during thyroidectomy, and share experiences regarding
preventing and treating its injury. Study Design Retrospective case data
analysis. Setting First Affiliated Hospital of Harbin Medical University.
Subjects and Methods Between January 2002 and May 2016, 7392 patients underwent
thyroidectomy in our hospital. Of them, 28 patients with NRLN were identified,
and their clinical data were retrospectively analyzed. Results This study
included 7392 patients in which the recurrent laryngeal nerves (RLNs) were
routinely identified during surgery. The presence of NRLN was intraoperatively
confirmed in 28 patients. All the NRLNs were located on the right side and its
overall incidence was 0.37%. Five of the NRLNs were classified as type I, 19 as
type IIa, and 4 as type IIb. Of the 28 cases, 4 NRLNs were injured during
surgery, in which primary end-to-end anastomosis or local seal with
corticosteroid injection was performed as a remedy. In the 4 patients with NRLN
injury, 2 presented with postoperative hoarseness that indicated vocal cord
paralysis confirmed by laryngoscope; the other 2 patients' voices had no
significant changes. Conclusion The NRLN, which is rare in clinical practice and
predominantly right-sided, is anatomically more complex and variant at a higher
risk of surgical injury. The key factors to accurately identify NRLN and to
effectively prevent its injury include careful interpretation of auxiliary
examination results before surgery, raising awareness of its presence, meticulous
dissection, and routine exposure of the RLN during surgery.
PMID- 28417661
TI - Corrective Nasal Surgery after Maxillomandibular Advancement for Obstructive
Sleep Apnea: Experience from 379 Cases.
AB - Objective Efficacy of maxillomandibular advancement (MMA) in the treatment of
obstructive sleep apnea (OSA) is associated with degree of maxillary advancement.
Large maxillary advancement leads to profound changes of the nasolabial region.
We present the incidence and indications of post-MMA corrective nasal surgery in
a large cohort. Study Design Case series with chart review. Setting University
medical center. Subjects and Methods A total of 379 subjects with OSA underwent
MMA at Stanford Hospital (surgeons: S.Y.L., R.W.R.) from August 1992 to December
2015. Data were collected on age, sex, American Society of Anesthesiologists
score, polysomnography parameters, and history of nasal surgery. Primary outcome
parameters were the incidence and indications of post-MMA corrective nasal
surgery. Results Of 379 subjects, the surgical success rate was 76.3% based on
the change in respiratory disturbance index. Seventy-one subjects (18.7%)
underwent corrective nasal surgery after MMA, whereas 48 underwent functional
nasal surgery and 23 underwent both functional and aesthetic nasal surgery. Lower
oxygen saturation nadir and higher baseline respiratory disturbance index were
associated with increased likelihood of post-MMA corrective nasal surgery.
Conclusion MMA surgical success is associated with degree of maxillary
advancement, which is especially significant in patients with severe OSA.
Patients must be counseled on its impact in nasal function and aesthetics. Our
series, the largest to date to address this question, suggests that the incidence
of post-MMA corrective nasal surgery is at least 18.7%. Prospectively, refinement
in MMA techniques is needed to minimize postoperative compromise in nasal form
and function.
PMID- 28417662
TI - Clinician views of patient decisional conflict when deciding between dialysis and
conservative management: Qualitative findings from the PAlliative Care in chronic
Kidney diSease (PACKS) study.
AB - BACKGROUND: Only a paucity of studies have addressed clinician perspectives on
patient decisional conflict, in making complex decisions between dialysis and
conservative management (renal supportive and palliative care). AIM: To explore
clinician views on decisional conflict in patients with end-stage kidney disease.
DESIGN: Interpretive, qualitative study. SETTING AND PARTICIPANTS: As part of the
wider National Institute for Health Research, PAlliative Care in chronic Kidney
diSease study, semi-structured interviews were conducted with clinicians
(nephrologists n = 12; 7 female and clinical nurse specialists n = 15; 15 female)
across 10 renal centres in the United Kingdom. Interviews took place between
April 2015 and October 2016 and a thematic analysis of the interview data was
undertaken. RESULTS: Three major themes with associated subthemes were
identified. The first, 'Frequent changing of mind regarding treatment options',
revealed how patients frequently altered their treatment decisions, some refusing
to make a decision until deterioration occurred. The second theme, 'Obligatory
beneficence', included clinicians helping patients to make informed decisions
where outcomes were uncertain. In weighing up risks and benefits, and the impact
on patients, clinicians sometimes withheld information they thought might cause
concern. Finally, 'Intricacy of the decision' uncovered clinicians' views on the
momentous and brave decision to be made. They also acknowledged the risks
associated with this complex decision in giving prognostic information which
might be inaccurate. LIMITATIONS: Relies on interpretative description which
uncovers constructed truths and does not include interviews with patients.
CONCLUSION: Findings identify decisional conflict in patient decision-making and
a tension between the prerequisite for shared decision-making and current
clinical practice. Clinicians also face conflict when discussing treatment
options due to uncertainty in equipoise between treatments and how much
information should be shared. The findings are likely to resonate across
countries outside the United Kingdom.
PMID- 28417663
TI - Is Neck Dissection Associated with an Increased Risk of Postoperative Stroke?
AB - Objective Prior studies have reported widely disparate rates of postoperative
stroke, with conflicting analyses of whether neck dissection is an independent
risk factor. Study Design Cohort study. Setting American College of Surgeons
National Surgical Quality Improvement Program from 2005 to 2013. Subjects and
Methods We compared the 30-day rate of postoperative stroke between patients
undergoing complete or modified radical neck dissection and a control cohort
composed of those undergoing resections in the oral cavity, oropharynx, larynx,
or hypopharynx without neck dissection. Propensity scores and paired statistics
were used to compare the groups while adjusting for relevant covariates. Results
We identified 9697 patients, including 5827 with neck dissection and 3870 without
neck dissection. In the full cohort, the rate of postoperative stroke was greater
with neck dissection than without it (0.31% vs 0.11%, P = .052), although the
relationship was attenuated by propensity score matching to adjust for
comorbidities (0.30% vs 0.13%, P = .18). Among patients with >=2 risk factors for
carotid artery stenosis, neck dissection was associated with an increased rate of
postoperative stroke (2.68% with bilateral neck dissection, 0.41% with unilateral
neck dissection, and 0.24% without neck dissection, P = .04). The incidence of
stroke was strongly associated with 30-day mortality (7.4% vs 0.2%, P < .001).
Conclusions Stroke is a rare but highly morbid complication after head and neck
surgery. Compared with other head and neck surgery, neck dissection in patients
at risk for carotid artery stenosis is associated with an increased risk of
postoperative stroke.
PMID- 28417664
TI - Low-dose systemic scopolamine disrupts context conditioning in rats.
AB - Cholinergic neurotransmission plays a key role in learning and memory. Prior
research with rats indicated that a low dose of pre-training scopolamine (0.1
mg/kg), a cholinergic receptor antagonist, did not affect cued fear conditioning,
but did block renewal when injected before extinguishing a conditioned tone,
opening up opportunities to pharmacologically improve exposure therapy for
anxiety patients. Before translating these findings to the clinic, it is
important to carefully examine how scopolamine affects contextual fear memories.
Here, we investigated the effects of scopolamine on encoding of contextual
anxiety and its generalization in male Wistar rats. We found a profound
disruption of context conditioning, suggesting that, even at a low dose, systemic
scopolamine may influence contextual encoding in the hippocampus, particularly
when the context is the best predictor for the presence of shocks.
PMID- 28417665
TI - Can Intracapsular Tonsillectomy Be an Alternative to Classical Tonsillectomy? A
Meta-analysis.
AB - Objective Tonsillectomy is the most common operation performed in the
otolaryngologic fields. Efforts have been made to reduce postoperative
complications, and one of these is intracapsular tonsillectomy and adenoidectomy
(ICTA), which leaves the tonsillar tissue with tonsillar capsule. This study
aimed to evaluate intracapsular tonsillectomy compared with classical
extracapsular tonsillectomy in terms of efficacy of the technique for managing
obstructive sleep apnea (OSA) and reducing postoperative complications. Data
Sources We performed a literature search using PubMed, EMBASE, and the Cochrane
Library through December 2016. Review Methods Summarized risk ratio (RR), risk
differences (RDs), and standardized mean differences (SMDs) with 95% confidence
intervals (CIs) were estimated by summarizing the risk estimates of each study
using random-effects models that considered both within- and between-study
variations. Results Our search included 15 randomized controlled studies. The RRs
for postoperative bleeding and residual tonsils were, respectively, 0.44 ( P =
.01) and 6.02 ( P = .0002). There were significant differences in postoperative
pain ( P = .0022), need for analgesics ( P < .0001), days to normal diet ( P =
.006), and days to normal activity ( P < .00001) between intracapsular
tonsillectomy and extracapsular tonsillectomy. Conclusions Intracapsular
tonsillectomy can effectively reduce postoperative pain and bleeding, which
shortens the time required to return to normal life. There was no difference
between microdebrider and coblator in intracapsular tonsillectomy regarding
postoperative pain and bleeding. It can increase the risk of remnant tonsils;
however, it does not increase the risk of recurrent infection.
PMID- 28417666
TI - Exploring the differential associations between components of executive
functioning and reactive and proactive aggression.
AB - OBJECTIVE: A large body of literature confirms the importance of executive
functioning (EF) in the explanation of aggressive and antisocial behaviors.
However, the common and specific associations between subtypes of aggression,
such as reactive (RA), proactive aggression (PA), and EF are unclear. The current
study explored the nuanced associations between components of EF and subtypes of
aggression, using a latent variable approach. METHOD: Participants were 384
racially diverse undergraduate students (ages 18-52 years) who completed a self
report measure of RA and PA, and traditional neuropsychological tasks of EF. The
appropriateness of using a nested bifactor model of EF was confirmed, and this
bifactor model of EF was then used to examine the specific associations between
components of EF and RA and PA. RESULTS: Results revealed that components of EF
are differentially associated with RA and PA. Specifically, impulsive, provoked
aggression (i.e., RA) was associated with lower levels of goal-oriented
inhibition and higher levels of flexibility, whereas planned, goal-oriented
aggression (i.e., PA) was associated with higher levels of working memory.
CONCLUSIONS: Findings from the current study underscore the importance of
considering the multidimensional nature of EF, as well as the heterogeneity
within aggression, rather than considering either construct as a single
monolithic construct. The current study suggests that potentially unique brain
based pathways from aspects of EF to subtypes of aggression may exist, and points
toward potential avenues through which to intervene.
PMID- 28417668
TI - Exploring molecular structural requirement for AChE inhibition through multi
chemometric and dynamics simulation analyses.
AB - The acetylcholinesterase enzyme (AChE) plays an important role in central and
peripheral nervous systems. Acetylcholine (ACh) acts through the regulation of
AChE activity, which can play a key role in accelerating senile amyloid beta
peptide (Abeta) plaque deposition. Therefore, inhibition of the AChE enzyme can
be used as a key principle to prevent ACh depletion. The present study has been
emphasized to explore both ligand- and structure-based 3D QSAR, HQSAR,
pharmacophore, molecular docking and simulation studies on a set of structurally
diverse inhibitors to optimize prime structural features responsible for
selective binding to AChE, and vis-a-vis inhibiting enzyme activity. The
pharmacophore model showed the importance of HB acceptor and donor, positive
ionization and hydrophobic features of the molecule for effective binding.
Structure-based docking and simulation studies adjudged the significance of
features obtained from ligand-based 3D QSAR, CoMFA (Q2 = .608, [Formula: see
text] = .700), CoMSIA (Q2 = .632, [Formula: see text] = .734), HQSAR (Q2 = .850,
[Formula: see text] = .693) and pharmacophore (Q2 = .839, ROCscore = .769)
models. The aim of the present study is to identify the essential structural and
physicochemical profiles of molecules that can provide therapeutic benefits with
less toxicity. Structurally diverse compounds have been used for the study, and
the generated models showed the large applicability domain.
PMID- 28417667
TI - Immediate and short-term biomechanical adaptation of habitual barefoot runners
who start shod running.
AB - This study investigated the immediate and short-term effects of minimalist shoes
(MS) and traditional running shoes (TRS) on vertical loading rates, foot strike
pattern and lower limb kinematics in a group of habitual barefoot runners. Twelve
habitual barefoot runners were randomly given a pair of MS or TRS and were asked
to run with the prescribed shoes for 1 month. Outcome variables were obtained
before, immediate after and 1 month after shoe prescription. Average and
instantaneous vertical loading rates at the 1-month follow-up were significantly
higher than that at the pre-shod session (P < 0.034, eta2p > 0.474). Foot strike
angle in the TRS group was significantly lower than that in the MS group (P =
0.045, eta2p = 0.585). However, there was no significant time nor shoe effect on
overstride, knee and ankle excursion (P > 0.061). Habitual barefoot runners
appeared to land with a greater impact during shod running and they tended to
have a more rearfoot strike pattern while wearing TRS. Lower limb kinematics were
comparable before and after shoe prescription. Longer period of follow-up is
suggested to further investigate the footwear effect on the running biomechanics
in habitual barefoot runners.
PMID- 28417669
TI - Structural basis for the regulation of phytohormone receptors.
AB - Phytohormones are central players in diverse plant physiological events, such as
plant growth, development, and environmental stress and defense responses. The
elucidation of their regulatory mechanisms through phytohormone receptors could
facilitate the generation of transgenic crops with cultivation advantages and the
rational design of growth control chemicals. During the last decade, accumulated
structural data on phytohormone receptors have provided critical insights into
the molecular mechanisms of phytohormone perception and signal transduction.
Here, we review the structural bases of phytohormone recognition and receptor
activation. As a common feature, phytohormones regulate the interaction between
the receptors and their respective target proteins (also called co-receptors) by
two types of regulatory mechanisms, acting as either "molecular glue" or an
"allosteric regulator." However, individual phytohormone receptors adopt specific
structural features that are essential for activation. In addition, recent
studies have focused on the molecular diversity of redundant phytohormone
receptors.
PMID- 28417670
TI - Case-Logging Practices in Otolaryngology Residency Training: National Survey of
Residents and Program Directors.
AB - Objective (1) Evaluate the consistency and manner in which otolaryngology
residents log surgical cases. (2) Assess the extent of instruction and guidance
provided by program directors on case-logging practices. Study Design Cross
sectional national survey. Setting Accreditation Council for Graduate Medical
Education otolaryngology residency programs in the United States. Subjects and
Methods US otolaryngology residents, postgraduate year 2 through graduating
chiefs as of July 2016, were recruited to respond to an anonymous questionnaire
designed to characterize surgical case-logging practices. Program directors of US
otolaryngology residency programs were recruited to respond to an anonymous
questionnaire to elucidate how residents are instructed to log cases. Results A
total of 272 residents and 53 program directors completed the survey, yielding
response rates of 40.6% and 49.5%, respectively. Perceived accuracy of case logs
is low among residents and program directors. Nearly 40% of residents purposely
choose not to log certain cases, and 65.1% of residents underreport cases
performed. More than 80% of program directors advise residents to log procedures
performed outside the operating room, yet only 16% of residents consistently log
such cases. Conclusion Variability in surgical case-logging behaviors and
differences in provided instruction highlight the need for methods to improve
consistency of logging practices. It is imperative to standardize practices
across otolaryngology residency programs for case logs to serve as an accurate
measure of surgical competency. This study provides a foundation for reform
efforts within residency programs and for the Resident Case Log System.
PMID- 28417672
TI - BOOK NOTICES.
PMID- 28417671
TI - The Use of Noninvasive Positive Pressure Ventilation following Pediatric
Tonsillectomy.
AB - Objective To determine the risks of bleeding and other complications in pediatric
patients who require noninvasive positive pressure ventilation (PPV) in the
immediate posttonsillectomy period. Study Design Case series with chart review.
Setting Single tertiary pediatric hospital. Subjects and Methods Sixty-nine
patients who had undergone tonsillectomy from July 2007 through December 2013 and
required postoperative PPV were reviewed. Data collected included age, sex,
medical history, preoperative polysomnogram parameters, length of use and type of
noninvasive ventilatory support, and postoperative complications. Bleeding rate
was calculated. Results Sixty-nine children met inclusion criteria for the study.
Most had comorbid conditions. The mean age of these patients was 6.4 years. The
postoperative bleeding rate of children who required operative intervention for
control was 5.97%. Patients did not experience other complications. Conclusion
This is the largest study in the literature investigating bleeding in pediatric
patients undergoing tonsillectomy who required postoperative noninvasive PPV.
Some hesitation may exist in using this form of ventilation when open pharyngeal
wounds are exposed to pressure, but this study suggests that it can be used as a
suitable alternative to invasive ventilation.
PMID- 28417673
TI - Research progress from the SCI Model Systems (SCIMS): An interactive discussion
on future directions.
AB - CONTEXT/OBJECTIVE: To describe current and future directions in spinal cord
injury (SCI) research. DESIGN: The SCI Model Systems (SCIMS) programs funded by
the National Institute on Disability, Independent Living, and Rehabilitation
Research (NIDILRR) during the 2011 to 2016 cycle provided abstracts describing
findings from current research projects. Discussion among session participants
generated ideas for research opportunities. SETTING/PARTICIPANTS: Pre-conference
workshop before the 2016 American Spinal Injury Association (ASIA) annual
meeting. A steering committee selected by the SCIMS directors that included the
moderators of the sessions at the ASIA pre-conference workshop, researchers
presenting abstracts during the session, and the audience of over 100 attending
participants in the pre-conference workshop. METHODS/RESULTS: Group discussion
followed presentations in 5 thematic areas of (1) Demographics and Measurement;
(2) Functional Training; (3) Psychosocial Considerations; (4) Assistive
Technology; and (5) Secondary Conditions. The steering committee reviewed and
summarized discussion points on future directions for research and made
recommendations for research based on the discussion in each of the five areas.
CONCLUSION: Significant areas in need of research in SCI remain, the goal of
which is continued improvement in the quality of life of individuals with SCI.
PMID- 28417674
TI - International Summit Consensus Statement: Intellectual Disability Inclusion in
National Dementia Plans.
AB - The World Health Organization (WHO) has called for the development and adoption
of national plans or strategies to guide public policy and set goals for
services, supports, and research related to dementia. It called for distinct
populations to be included within national plans, including adults with
intellectual disability (ID). Inclusion of this group is important as having
Down's syndrome is a significant risk factor for early-onset dementia. Adults
with other ID may have specific needs for dementia-related care that, if unmet,
can lead to diminished quality of old age. An International Summit on
Intellectual Disability and Dementia, held in Scotland, reviewed the inclusion of
ID in national plans and recommended that inclusion goes beyond just description
and relevance of ID. Reviews of national plans and reports on dementia show
minimal consideration of ID and the challenges that carers face. The Summit
recommended that persons with ID, as well as family carers, should be included in
consultation processes, and greater advocacy is required from national
organizations on behalf of families, with need for an infrastructure in health
and social care that supports quality care for dementia.
PMID- 28417676
TI - Bio-energy generation in an affordable, single-chamber microbial fuel cell
integrated with adsorption hybrid system: effects of temperature and comparison
study.
AB - : A microbial fuel cell (MFC) integrated with adsorption system (MFC-AHS) is
tested under various operating temperatures with palm oil mill effluent as the
substrate. The optimum operating temperature for such system is found to be at
~35 degrees C with current, power density, internal resistance (Rin), Coulombic
efficiency (CE) and maximum chemical oxygen demand (COD) removal of 2.51 +/- 0.2
mA, 74 +/- 6 mW m-3, 25.4 Omega, 10.65 +/- 0.5% and 93.57 +/- 1.2%, respectively.
Maximum current density increases linearly with temperature at a rate of 0.1772
mA m-2 degrees C-1, whereas maximum power density was in a polynomial function.
The temperature coefficient (Q10) is found to be 1.20 between 15 degrees C and 35
degrees C. Present studies have demonstrated better CE performance when compared
to other MFC-AHSs. Generally, MFC-AHS has demonstrated higher COD removals when
compared to standalone MFC regardless of operating temperatures. ABBREVIATIONS:
ACFF: activated carbon fiber felt; APHA: American Public Health Association; CE:
Coulombic efficiency; COD: chemical oxygen demand; ECG: electrocardiogram; GAC:
granular activated carbon; GFB: graphite fiber brush; MFC: microbial fuel cell;
MFC-AHS: microbial fuel cell integrated with adsorption hybrid system; MFC-GG:
microbial fuel cell integrated with graphite granules; POME: palm oil mill
effluent; PTFE: polytetrafluoroethylene; SEM: scanning electron microscope.
PMID- 28417677
TI - Descriptive Epidemiology of Hypertension and Its Association With Obesity: Based
on the WHO STEPwise Approach to Surveillance in Palau.
AB - The rise of noncommunicable diseases is a serious health burden for Palau. This
study described the prevalence of hypertension, and assessed its association with
obesity. Surveys following the WHO STEPwise approach to surveillance were
conducted in 2529 adults. Multivariate prevalence ratios (PR) of hypertension for
body mass index (BMI) categories were calculated by logistic regression models
using conditional standardization procedure. Age- and sex-specified analyses were
performed. Overall prevalence of obesity and hypertension were 40.4% and 46.8%,
respectively. Prevalence of hypertension was positively associated with BMI.
However, overweight men had as high prevalence of hypertension as the obese
(multivariable-adjusted PR was 1.84 for overweight and 1.91 for obese compared
with nonoverweight). The association between hypertension and BMI was similar
across age groups. The prevalence of hypertension in women increased gradually
with the increase of BMI whereas that in men reached a plateau already in the
overweight.
PMID- 28417678
TI - Changes in peripheral blood T-cell balance after percutaneous tumor ablation.
AB - PURPOSE: To evaluate the changes in T-cell balance in peripheral blood following
percutaneous tumor ablation. MATERIAL AND METHODS: Patients underwent thermal
ablation including radiofrequency (n = 9) and microwave ablation (n = 5), or
cryoablation (n = 5). Target tumors were located in the lung (n = 7), soft tissue
(n = 5), liver (n = 4), and bone (n = 3). Patient peripheral blood samples were
collected before and within 14 days after ablation. Peripheral blood populations
of cytotoxic T-cells (CTL), type-1 (Th1) and type-2 helper T-cells (Th2), and
regulatory T-cells (Treg) were measured using flow cytometry. Changes in CTL/Treg
and Th1/Th2 ratios before and after ablation therapy were compared using paired t
tests. RESULTS: Peripheral blood CTL population (27.5 +/- 2.1% to 30.2 +/- 2.5%,
p < .03) and CTL/Treg ratios (18.8 +/- 3.7% to 21.6 +/- 3.6%, p < .05) increased
significantly after ablation. Although a significant increase in CTL/Treg ratios
was found after heat-based ablation (18.0 +/- 4.4% to 21.6 +/- 4.7%, p < .02), it
remained unchanged after cryoablation (21.0 +/- 7.0% to 21.5 +/- 4.3%, p = .92).
Th1/Th2 ratio (13.7 +/- 3.0% to 17.2 +/- 3.5%, p = .12) remained unchanged after
ablation. CONCLUSION: Ablation therapy alters the T-cell balance by increasing
the systemic CTL/Treg, ratio. Heat-based ablation might be a more effective
approach than cryoablation to enhance systemic anti-tumor immunity.
PMID- 28417679
TI - Synergy or interference of a H9N2 avian influenza virus with a velogenic
Newcastle disease virus in chickens is dose dependent.
AB - Field observations indicate that the impact of velogenic Newcastle disease virus
(vNDV) is more severe in countries with concomitant circulation of low
pathogenicity avian influenza virus, as is the case in the Middle East, in
particular in Israel, where H9N2 and NDV are endemic. In our study, we evaluated
how the exposure of chickens to an H9N2 challenge either favours or interferes
with a subsequent vNDV infection and its transmission to sentinels. For this
purpose, single vNDV and sequential H9/NDV challenges were performed with
increasing doses of vNDV (101-106 EID50). The H9N2 challenge made birds more
susceptible to the vNDV, lowering the minimum dose required to cause an
infection, exacerbating the clinical outcome, while delaying the onset of the
disease and time of death. Interestingly, the presence and degree of these
seemingly contrasting effects were dose-dependent and not mutually exclusive.
PMID- 28417680
TI - Designing medical internships to improve recruitment and retention of doctors in
rural areas.
AB - BACKGROUND: The medical internship as a way of exposing young doctors to training
in a rural context is regarded as a useful tool to recruit and retain doctors in
rural areas. Norwegian health authorities tested an arrangement of early sign-up
for medical internships in the Finnmark County in Norway. OBJECTIVE: To report on
the effects of the early sign-up for medical internship. DESIGN: This study
compares the choice of workplace after internship among physicians who signed up
early with those candidates assigned to the raffle model of internship in the
study area, and in a comparison area experiencing similar recruitment and
retention problems. RESULTS: The proportion of interns who signed up early that
still worked as physicians in the study area by April 2014 (29%) was twice as
high as among the regular interns (15%) and interns in the comparison area (14%).
Among the 59 interns who signed up early still working in the study area in April
2014, 33% had grown up in this area. However, the greatest benefits were for the
most densely populated municipalities in the study area. CONCLUSIONS: The early
sign-up model had a net contribution of proving additional physicians in the
study area.
PMID- 28417681
TI - Proximal femoral nail antirotation versus dynamic hip screw fixation for
treatment of osteoporotic type 31-A1 intertrochanteric femoral fractures in
elderly patients.
AB - Objective To evaluate long-term radiographic and functional outcomes between
dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA) fixation
for treatment of osteoporotic type 31-A1 intertrochanteric femoral fractures
(IFFs) among elderly patients Methods A retrospective comparative study was
carried out. Follow-up was performed at 1, 3, 6, 9, and 12 months postoperatively
and yearly thereafter. The primary outcome was the radiographic outcome, and the
secondary outcome was the functional outcome. Results A significant difference in
radiographic complications was observed between the DHS group (n = 45, 40.2%) and
PFNA group (n = 15, 13.6%). The risk of femoral shaft fracture after implant
removal at the 1-year follow-up was increased by 0.9% (n = 1) and 6.3% (n = 7) in
the PFNA and DHS groups, respectively. This difference persisted with rates of
3.6% (n = 4) and 12.5% (n = 14) at the final follow-up. Additionally, significant
differences were present in the Harris hip score at each visit. Conclusion Our
results indicate that PFNA yields better outcomes than DHS fixation among elderly
patients with osteoporotic type 31-A1 IFFs.
PMID- 28417682
TI - Does Social Support Buffer the Association Between Stress Eating and Weight Gain
During the Transition to College? Differences by Gender.
AB - This study sought to examine whether social support moderates the relationship
between stress eating and body mass index (BMI) change over the freshman year in
males and females. This longitudinal study included 70 college students (72.9%
female; M age = 18.23) who completed self-reported measures of stress eating and
perceived social support, with objective height and weight measurements
collected. Among males, social support moderated the relationship between stress
eating and BMI change. Among males, social support may serve as a buffer against
the impact of stress eating on weight gain during the freshman year of college.
PMID- 28417683
TI - Tracheostomy for Severe Pediatric Obstructive Sleep Apnea: Indications and
Outcomes.
AB - Objectives (1) To describe characteristics of pediatric patients undergoing
tracheostomy for obstructive sleep apnea (OSA). (2) To highlight perioperative
events and outcomes of the procedure. Study Design Case series with chart review.
Setting Four tertiary care academic children's hospitals. Subjects and Methods
Twenty-nine children aged <18 years from January 1, 2010, to December 31, 2015,
who underwent tracheostomy for severe OSA, defined as an apnea-hypopnea index
(AHI) >10, were included in the study. Data on patient characteristics,
polysomnographic findings, comorbidities, and perioperative events and outcomes
were collected and analyzed. Results Twenty-nine patients were included. Mean age
at tracheostomy was 2.0 years (95% CI, -2.2 to 6.2). Mean body mass index z score
was -1.2 (95% CI, -4.9 to -2.5). Mean preoperative AHI was 60.2 (95% CI, -15.7 to
136.1). Mean postoperative intensive care unit stay was 23.2 days (95% CI, 1.44
45.0). One procedure was complicated by bronchospasm. Thirteen patients had
craniofacial abnormalities; 10 had a neurologic disorder resulting in hypotonia;
and 5 had a diagnosis of laryngomalacia. Mean follow-up was 30.6 months (95% CI,
10.4 to 71.6). Six patients were decannulated, with a mean time to decannulation
of 40.8 months (95% CI, 7.9-73.7). Five patients underwent capped sleep study
prior to decannulation with a mean AHI of 6.6 (95% CI, -9.9 to 23.1) and a mean
oxygen nadir of 90.0% (95% CI, 80%-100%). Conclusion OSA is an uncommon
indication for tracheostomy in children. Patients who require the procedure
usually have an associated syndromic diagnosis resulting in upper airway
obstruction. The majority of children who undergo tracheostomy for OSA will
remain dependent at 24 months.
PMID- 28417685
TI - Independent socio-demographic and clinical correlates associated with the
perception of quality of life of women with postpartum depressionin North
central, Nigeria.
AB - OBJECTIVE: Quality of life (QoL) is probably the most desired outcome of all
health care policies and monitoring. This concept is seldom used on women in the
postpartum, especially in the developing world. AIM: This study aimed at
determining the independent socio-clinical variables associated with the
perception of QoL of women with postpartum depression. METHODS: A two-stage cross
sectional procedure was used to recruit 550 participants, out of whom 531
participants completed the questionnaires with 116 participants found to have
postpartum depression and were the studied population, in Nigeria. The Socio
demographic questionnaire, the Edinburgh Postnatal Depression Scale, the World
Health Organization Quality of Life-Bref-26 and the Depression Module of the
Structured Clinical Interview for DSM-IV axis I Diagnosis were used. RESULTS:
Participants with postpartum depression had significantly poor perception of QoL
in all the four domains of the WHOQoL-BREF-26. The independent socio-demographic
and clinical correlate associated with poor perception for both rating of QoL and
satisfaction with health was education (beta = 0.321, p < .001 and beta = 0.0326,
p = .002, respectively); for physical domain [(modes of delivery) (beta = -0.28,
p = .016)]; psychological domain [(age <35years) (beta = 0.391, p = .010)] and
for social relationships [(complications during delivery) (beta = 0.257, p =
.043)]. CONCLUSIONS: The determination of the predictors of QoL, which is an
indicator of disease outcome will improve service delivery to women of
childbearing age.
PMID- 28417686
TI - Trauma epidemiology in Puerto Rico: in-hospital morbidity and mortality from 2002
to 2011.
AB - This study aimed to describe the distribution of injury mechanisms and to assess
the impact of those mechanisms on the morbidity and mortality of trauma. All
patients admitted to Puerto Rico Trauma Hospital (2002-2011) for road-traffic
collisions (RTCs, 5,371), gunshot wounds (GSWs, 2,946), falls (2,319), pedestrian
accidents (1,652), and stab wounds (SWs, 1,073) were selected. Gunshot victims
were 1.19 (95%CI: 1.07-1.33) times as likely as road-traffic victims to have an
ISS >=25. Pedestrians were 1.76 (95%CI: 1.49-2.09) times more likely to have a
GCS <=8 than road-traffic victims were. The risk of dying was 2.64 (95%CI: 2.20
3.16) times higher for gunshot victims and 1.51 (95%CI: 1.23-1.86) times higher
for pedestrians compared to patients who had had RTCs. Gunshot victims and
pedestrians had the worst clinical outcomes. Accordingly, these patients should
receive the most aggressive clinical management. Furthermore, it is imperative to
develop public health campaigns on trauma prevention.
PMID- 28417687
TI - Does a perceptuomotor skills assessment have added value to detect talent for
table tennis in primary school children?
AB - Talent detection intends to support lifelong sports participation, reduce
dropouts and stimulate sports at the elite level. For this purpose it is
important to reveal the specific profile which directs children to the sports
that connect to their strengths and preferences. This study evaluated a
perceptuomotor skills assessment as part of talent detection for table tennis, a
sport in which perceptuomotor skills are considered essential to cope with the
difficult technical aspects. Primary school children (n = 121) and gifted young
table tennis players (n = 146) were assessed using the Dutch perceptuomotor
skills assessment measuring "ball control" and "gross motor function". A
discriminant function analysis confirmed the added value by identifying primary
school children fitting the table tennis perceptuomotor profile of the young
gifted table tennis players (28%). General linear model analyses for the
assessment's individual test items showed that the table tennis players
outperformed their primary school peers on all "ball control" items (P < 0.001).
In conclusion, the assessment appears to be of added value for talent detection
in table tennis at this young age. Longitudinal studies need to reveal the
predictive value for sports participation and elite sports.
PMID- 28417688
TI - Medical professionalism frameworks across non-Western cultures: A narrative
overview.
AB - BACKGROUND: Medical professionalism is context-specific, but most literature on
professionalism stems from Western countries. This study is about benchmarking of
different frameworks on professionalism and interpreting the commonalities and
discrepancies of understanding professionalism across different cultures. We need
to study the cultural underpinning of medical professionalism to graduate future
"global" practitioners who are culturally sensitive enough to recognize
differences (and also similarities) of expectations of patients in various
contexts. AIM: This study aims at describing culture specific elements of three
identified non-Western frameworks of professionalism, as well as their
commonalities and differences. METHOD: A narrative overview was carried out of
studies that address professionalism in non-Western cultures in the period 2002
2014. RESULTS: Out of 143 articles on medical professionalism, only four studies
provided three structured professionalism frameworks in non-Western contexts.
Medical professionalism attributes in non-Western cultures were influenced by
cultural values. Out of the 24 identified attributes of professionalism, 3
attributes were shared by the three cultures. Twelve attributes were shared by at
least two cultures, and the rest of the attributes were unique to each culture.
CONCLUSIONS: The three frameworks provided culture-specific elements in a unique
conceptual framework of medical professionalism according to the region they
originated from. There is no single framework on professionalism that can be
globally acknowledged. A culture-oriented concept of professionalism is necessary
to understand what the profession is dedicated to and to incorporate the concept
into the medical students' and physicians' professional identity formation.
PMID- 28417684
TI - Toward a multiscale modeling framework for understanding serotonergic function.
AB - Despite its importance in regulating emotion and mental wellbeing, the complex
structure and function of the serotonergic system present formidable challenges
toward understanding its mechanisms. In this paper, we review studies
investigating the interactions between serotonergic and related brain systems and
their behavior at multiple scales, with a focus on biologically-based
computational modeling. We first discuss serotonergic intracellular signaling and
neuronal excitability, followed by neuronal circuit and systems levels. At each
level of organization, we will discuss the experimental work accompanied by
related computational modeling work. We then suggest that a multiscale modeling
approach that integrates the various levels of neurobiological organization could
potentially transform the way we understand the complex functions associated with
serotonin.
PMID- 28417689
TI - A Bayesian hierarchical model for discrete choice data in health care.
AB - In discrete choice experiments, patients are presented with sets of health states
described by various attributes and asked to make choices from among them.
Discrete choice experiments allow health care researchers to study the
preferences of individual patients by eliciting trade-offs between different
aspects of health-related quality of life. However, many discrete choice
experiments yield data with incomplete ranking information and sparsity due to
the limited number of choice sets presented to each patient, making it
challenging to estimate patient preferences. Moreover, methods to identify
outliers in discrete choice data are lacking. We develop a Bayesian hierarchical
random effects rank-ordered multinomial logit model for discrete choice data.
Missing ranks are accounted for by marginalizing over all possible permutations
of unranked alternatives to estimate individual patient preferences, which are
modeled as a function of patient covariates. We provide a Bayesian version of
relative attribute importance, and adapt the use of the conditional predictive
ordinate to identify outlying choice sets and outlying individuals with unusual
preferences compared to the population. The model is applied to data from a study
using a discrete choice experiment to estimate individual patient preferences for
health states related to prostate cancer treatment.
PMID- 28417690
TI - Global scientific production in the field of knee arthroplasty: A cross-sectional
survey of research activities.
AB - Objective To determine the quantity and quality of articles in the field of knee
arthroplasty worldwide and elucidate the characteristics of global scientific
production. Methods Web of Science was used to identify articles in the field of
knee arthroplasty from 2011 to 2015. The total number of papers, number of papers
per capita, total number of citations, and mean number of citations were
collected. Results In total, 11,590 papers were identified. The number of
publications significantly increased from 2011 to 2015. Most originated from
North America, East Asia, and West Europe. Most (88.51%) were from high-income
countries, 11.48% were from middle-income countries, and only 0.01% were from
lower-income countries. The United States had the most articles and total
citations. Sweden had the highest mean citations, followed by Denmark and Canada.
However, when adjusted by population size, Denmark had the most articles per
million population, followed by Switzerland and the Netherlands. Conclusions The
number of knee arthroplasty publications has rapidly increased in recent years.
The United States is the most prolific, but some European countries are more
productive relative to their population.
PMID- 28417691
TI - Telangiectasias in Osler-Weber-Rendu Syndrome.
PMID- 28417692
TI - Autobiographical remembering regulates emotions: a functional perspective.
AB - Emotional deviation has been considered an essential factor in emotion
regulation, in that, attempts to compensate for the deviation is reflected on
cognitive processes. In the present study, we focused on autobiographical
remembering and tested the functional role of memory on emotion regulation. We
specifically examined the congruence effect in individuals' subsequent memory
reports after recalling emotional events. Individuals were randomly assigned to
three groups to report either sadness or anger evoking events or emotionally
unspecified events that they experienced in the last five years. Results
supported mood-incongruence, but only for the emotional memory groups. Despite
highly negative memories reported in the initial recall, individuals in anger-
and sad-memory groups revealed an up-regulation trend in subsequent recall.
Furthermore, sadness and anger induction affected phenomenological features of
the subsequently reported memory. Overall, our findings supported for the emotion
regulation function of remembering that serves counter-regulation of the negative
emotion. We discuss potential mechanisms in the light of explanations by a
functional approach to autobiographical memory.
PMID- 28417694
TI - Association between environmental contaminants and health outcomes in indigenous
populations of the Circumpolar North.
AB - Background Since the 1990s, research has been carried out to monitor
environmental contaminants and their effects on human health in the Arctic.
Although evidence shows that Arctic indigenous peoples are exposed to higher
levels of contaminants and do worse on several dimensions of health compared with
other populations, the contribution of such exposures on adverse outcomes is
unclear. Objective The purpose of this review is to provide a synopsis of the
published epidemiological literature that has examined association between
environmental contaminants and health outcomes in Arctic indigenous populations.
Design A literature search was conducted in OVID Medline (1946-January 2014)
using search terms that combined concepts of contaminant and indigenous
populations in the Arctic. No language or date restrictions were applied. The
reference lists of review articles were hand-searched. Results Of 559 citations,
60 studies were relevant. The studies fell under the following categories:
paediatric (n=18), reproductive health (n=18), obstetrics and gynaecology (n=9),
cardiology (n=7), bone health (n=2), oncology (n=2), endocrinology (n=2) and
other (n=2). All studies, except one from Arctic Finland, were either from
Nunavik or Greenland. Most studies assessed polychlorinated biphenyls (n=43) and
organochlorine pesticides (n=29). Fewer studies examined heavy metals,
perfluorinated compounds, or polybrominated diphenyl ethers. Details of study
results for each health category are provided. Conclusions It is difficult to
make conclusive statements about the effects of environmental contaminants on
health due to mixed results, small number of studies and studies being restricted
to a small number of regions. Meta-analytical synthesis of the evidence should be
considered for priority contaminants and health outcomes. The following research
gaps should be addressed in future studies: association of contaminants and
health in other Arctic regions (i.e. Inuvialuit Settlement Region, Nunavut,
Nunatsiavut, Alaska, European North and Russian North); assessment of
contaminants on chronic diseases; inclusion of clinical endpoints in assessments;
and assessment of the emerging contaminants of perfluorinated compounds and
polybrominated diphenyl ethers.
PMID- 28417695
TI - A mixed methods inquiry into the determinants of traditional food consumption
among three Cree communities of Eeyou Istchee from an ecological perspective.
AB - Background The Aboriginal nations of Canada have higher incidences of chronic
diseases, coinciding with profound changes in their environment, lifestyle and
diet. Traditional foods can protect against the risks of chronic disease.
However, their consumption is in decline, and little is known about the complex
mechanisms underlying this trend. Objective To identify the factors involved in
traditional food consumption by Cree Aboriginal people living in 3 communities in
northern Quebec, Canada. Design A mixed methods explanatory design, including
focus group interviews to interpret the results of logistic regression. Methods
This study includes a secondary data analysis of a cross-sectional survey of 3
Cree communities (n=374) and 4 focus group interviews (n=23). In the first,
quantitative phase of the study, data were collected using a food-frequency
questionnaire along with a structured questionnaire. Subsequently, the focus
group interviews helped explain and build on the results of logistic regressions.
Results People who consume traditional food 3 days or more weekly were more
likely to be 40 years old and over, to walk 30 minutes or more per day, not to
have completed their schooling, to live in Mistissini and to be a hunter (p<0.05
for all comparisons). The focus group participants provided explanations for the
quantitative analysis results or completed them. For example, although no
statistical association was found, focus group participants believed that
employment acts as both a facilitator and a barrier to traditional food
consumption, rendering the effect undetectable. In addition, focus group
participants suggested that traditional food consumption is the result of
multiple interconnected influences, including individual, family, community and
environmental influences, rather than a single factor. Conclusions This study
sheds light on a number of factors that are unique to traditional foods, factors
that have been understudied to date. Efforts to promote and maintain traditional
food consumption could improve the overall health and wellbeing of Cree
communities.
PMID- 28417696
TI - BOOK NOTICES.
PMID- 28417697
TI - Case-control study of breast cancer and exposure to synthetic environmental
chemicals among Alaska Native women.
AB - Background Exposure to environmental chemicals may impair endocrine system
function. Alaska Native (AN) women may be at higher risk of exposure to these
endocrine disrupting chemicals, which may contribute to breast cancer in this
population. Objective To measure the association between exposure to select
environmental chemicals and breast cancer among AN women. Design A case-control
study of 170 women (75 cases, 95 controls) recruited from the AN Medical Center
from 1999 to 2002. Participants provided urine and serum samples. Serum was
analyzed for 9 persistent pesticides, 34 polychlorinated biphenyl (PCB)
congeners, and 8 polybrominated diethyl ether (PBDE) congeners. Urine was
analyzed for 10 phthalate metabolites. We calculated geometric means (GM) and
compared cases and controls using logistic regression. Results Serum
concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB
153, PCB-180) were lower in case women than controls. BDE-47 was significantly
higher in case women (GM=38.8 ng/g lipid) than controls (GM=25.1 ng/g lipid)
(p=0.04). Persistent pesticides, PCBs, and most phthalate metabolites were not
associated with case status in univariate logistic regression. The odds of being
a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP)
concentrations that were above the median; this relationship was seen in both
univariate (OR 2.16, 95% CI 1.16-4.05, p=0.02) and multivariable (OR 2.43, 95% CI
1.13-5.25, p=0.02) logistic regression. Women with oestrogen receptor (ER)
/progesterone receptor (PR)-tumour types tended to have higher concentrations of
persistent pesticides than did ER+/PR+ women, although these differences were not
statistically significant. Conclusions Exposure to the parent compound of the
phthalate metabolite MEHP may be associated with breast cancer. However, our
study is limited by small sample size and an inability to control for the
confounding effects of body mass index. The association between BDE-47 and breast
cancer warrants further investigation.
PMID- 28417698
TI - Vitamin D status of northern indigenous people of Russia leading traditional and
"modernized" way of life.
AB - Background Vitamin D status in groups of northern indigenous people of Russia
leading close to traditional (seminomadic reindeer herding), post-traditional (in
settlements) or "modernized" (in towns) way of life was analysed. Design The
survey study groups consisted of 178 Nenets and Komi aged 18-60 living in the
Arctic (66-67 degrees N). Urban Komi, Udmurts and Komi-Permiaks (n=150) living in
a non-Arctic area (57-61 degrees N) formed a control group. The concentration of
serum 25-hydroxyvitamin D (25OHD), as a transport form of vitamin D, was assessed
by enzyme immunoassay analysis. Results The group average 25OHD levels in both
rural and urban Arctic residents are within the range of values seen in the non
Arctic urban subjects adjusted for season: 39.7-47.7 nmol/l. Abandoning
traditional lifestyle associates with lower vitamin D levels in indigenous Arctic
people. Mean+/-standard deviation 25OHD values among Nenets were lower in those
living in the administrative centre (a big settlement) with a population of 1,460
(32.2+/-12.90 nmol/l) than in the residents of small settlements (39.6+/-14.08
nmol/l), and in reindeer herders (42.4+/-13.45 nmol/l; p<0.05 in both cases).
Komi townspeople had lower 25OHD concentrations (47.7+/-12.00 nmol/l) than Komi
reindeer herders (68.7+/-25.20; p<0.01). Conclusions The transition from
seminomadic to post-traditional and "modernized" way of life has led to a
decrease in the consumption of traditional foods among the indigenous people of
the Russian Arctic. Our data support the notion that the traditional northern
diet promotes healthy vitamin D levels, while adherence to the "western" type of
diet correlates with a lower 25OHD concentration.
PMID- 28417700
TI - Editorial - the state of the journal.
PMID- 28417699
TI - Periodontal status among patients with diabetes in Nuuk, Greenland.
AB - Background Diabetes is becoming more common in the Greenlandic population.
Patients with diabetes are more prone to periodontal disease. Periodontal status
may have an effect on metabolic control. Objective The aim of this study was to
estimate the prevalence of periodontitis amongst patients with diabetes in Nuuk,
Greenland, and secondly, to observe if dental care was associated with improved
periodontal status and metabolic control. Study design Observational cross
sectional study and a pilot study of a dental care intervention. Methods Sixty
two Greenlandic patients with diabetes were included in the study. Data were
collected from the Electronic Medical Records (EMR), in addition to a telephone
interview. Patients were offered 3 dental examinations with a 3-month interval.
The dental examinations consisted of a full-mouth assessment of number of
remaining teeth and assessment of periodontal status. Patients received scaling
and root planing, together with information and instructions on oral hygiene.
Information on glycated haemoglobin (HbA1C) values was collected from the EMR at
each dental examination. Results In this study, 21.0% (13/62) of patients with
diabetes had periodontitis. About 42% had less than 20 teeth. The association
between diabetes and periodontitis was known by 20 out of the 62 patients. Over
half of the patients had been to a dental examination within the last year. The
prevalence of periodontitis decreased significantly from 21.0 to 0% (p<0.001)
after 3 dental examinations. No change in HbA1C levels was observed (p=0.440).
Conclusion Periodontitis was common among patients with diabetes in Nuuk. Dental
health status based on Periodontal Screening Index (PSI) and bleeding on probing
(BOP) seemed to improve after dental health care, indicating a need for increased
awareness among patients and health care professionals. HbA1C levels were not
improved among the patients.
PMID- 28417701
TI - Survey of hand surgeons' and therapists' perceptions of the benefit of common
surgical procedures of the hand.
AB - OBJECTIVE: The objectives of this survey were (1) to study if surgeons'
perceptions of the benefit of six surgical procedures differ if they consider
themselves as patients instead of treating a patient, (2) to evaluate the role of
five predetermined factors that may influence decision-making, and (3) to assess
how uniformly hand surgeons and hand therapists perceive the benefits of the
surgical treatments. METHODS: The members of the national societies for Hand
Surgery and Hand Therapy were asked to participate in the survey. Six patient
cases with hand complaint (carpal tunnel syndrome, flexor tendon injury, dorsal
wrist ganglion, thumb amputation, boxer's fracture, and mallet fracture) and a
proposed operative procedure were presented, and the respondents rated the
procedures in terms of the expected benefit. Half of the surgeons were advised to
consider themselves as patients when filling out the survey. RESULTS: A survey
was completed by 56 surgeons (61%) and 59 therapists (20%). Surgeons who
considered themselves as patients had less confident perception on the benefit of
carpal tunnel release compared with surgeons, who considered treating patients.
Hand surgeons and hand therapists had similar perception of the benefits of
surgery. The expected functional result was regarded as the most important factor
in directing the decision about the treatment. CONCLUSIONS: Surgeons tended to be
more unanimous in their opinions in cases, where there is limited evidence on
treatment effect. The agreement between surgeons and therapists implies that the
clinical perspectives are similar, and probably reflect the reality well.
PMID- 28417702
TI - Quinolone resistance-associated amino acid substitutions affect enzymatic
activity of Mycobacterium leprae DNA gyrase.
AB - Quinolones are important antimicrobials for treatment of leprosy, a chronic
infectious disease caused by Mycobacterium leprae. Although it is well known that
mutations in DNA gyrase are responsible for quinolone resistance, the effect of
those mutations on the enzymatic activity is yet to be studied in depth. Hence,
we conducted in vitro assays to observe supercoiling reactions of wild type and
mutated M. leprae DNA gyrases. DNA gyrase with amino acid substitution Ala91Val
possessed the highest activity among the mutants. DNA gyrase with Gly89Cys showed
the lowest level of activity despite being found in clinical strains, but it
supercoiled DNA like the wild type does if applied at a sufficient concentration.
In addition, patterns of time-dependent conversion from relaxed circular DNA into
supercoiled DNA by DNA gyrases with clinically unreported Asp95Gly and Asp95Asn
were observed to be distinct from those by the other DNA gyrases.
PMID- 28417703
TI - Central pedicle reduction mammaplasty with a vertical scar: a technical
modification.
AB - BACKGROUND: This study introduces a central pedicle reduction mammaplasty with a
vertical scar technique. OBJECTIVES: This study is aimed to create a more conical
breast shape and long-lasting better projection by modifying reduction
mammaplasty by central pedicle flap. METHOD: Preoperative markings were made
including the meridian line of breast and the new location of the nipple-areola
complex (NAC). The new location of the inframammary fold was marked ~2 ~ 4 cm
above the original inframammary fold. An incision was made around the areola, the
area between the resection margins and NAC was excised en bloc. The breast
parenchyma was excised circumferentially, so that a cone shaped central mound was
formed. An inferior and inferolateral glandular resection was performed to reduce
the area of the breast base by elevating the position of the inframammary fold.
After completion of dissection, the central pedicle surmounted by the NAC was
transposed to its new location. RESULT: Fifty-six patients were operated with our
modified central pedicle technique. The mean amount of resection was 475 g (range
= 130-1080 g). The mean length of follow-up was 18 months (range = 12-53 months).
The mean postoperative satisfaction score was 4.23 (SD = 0.81). The breast
parenchymal ratio significantly increased from 1.2 preoperatively to 3.9
postoperatively. CONCLUSION: The modified central pedicle reduction mammaplasty
with a vertical scar technique is a versatile breast reduction technique for all
shapes and tissue conditions, by providing an attractive conical shape of the
breast with minimum scar burden and maximum preservation of breast function.
PMID- 28417704
TI - Effects of Silver Nitrate Cauterization on Middle Turbinate Synechia after
Endoscopic Sinus Surgery.
AB - Objective This study aimed to examine the efficacy of silver nitrate
cauterization of the middle turbinate (MT) for hindering postoperative middle
meatal synechia formation after endoscopic sinus surgery (ESS). Study Design
Prospective, controlled, and single-blinded. Settings Tertiary referral center.
Subjects and Methods For this study, 38 patients undergoing bilateral ESS due to
nasal polyposis were recruited. Following ESS, silver nitrate cauterization of
the lateral side of the left MT was performed in all cases. The noncauterized
opposite right sides served as controls. All patients received the standard ESS
protocol, intraoperative middle meatal packing, and postoperative management. The
main outcome measured was the formation of partial or complete MT synechia at the
end of 6-month assessment, performed by a blinded observer. Results At the end of
the 6-month follow-up period, MT synechia formation was observed in 7 of the
right sides (7 of 38, 18.4%) and none in any left sides. The rate of synechia
formation was significantly higher in the controls when compared with the silver
nitrate-cauterized sides ( P < .001). Conclusion The results of this study
suggest that silver nitrate cauterization of the MT is a practical and efficient
method to eliminate middle meatal synechia after ESS.
PMID- 28417707
TI - Report from the Secretaries General of the Royal Belgian Society for Surgery The
Next Step.
PMID- 28417705
TI - Degradation of staphylococcal enterotoxin A by a Pseudomonas aeruginosa isolate
from raw milk.
AB - Recently, we found that staphylococcal enterotoxin A (SEA)-producing
Staphylococcus aureus strains produced SEA in raw milk with microbial
contaminants at high temperatures like 40 degrees C only. Moreover, the
concentration of SEA produced in raw milk gradually decreased after the peak. The
reason(s) for SEA degradation in raw milk was studied in this study. Degradation
of SEA spiked in raw milk was observed at 40 degrees C, but not at 25 degrees
C. A Pseudomonas aeruginosa isolate from raw milk degraded SEA spiked in broth at
40 degrees C. A sample partially purified with a chromatographic method from
culture supernatant of the isolate degraded SEA. Two main proteolytic bands were
observed in the sample by zymographic analysis with casein. These results
suggested that the SEA in raw milk might be degraded by a protease(s) produced by
the P. aeruginosa isolate. This finding might be the first report on SEA
degradation by a proteolytic enzyme(s) derived from Pseudomonas bacteria to our
knowledge.
PMID- 28417713
TI - Caring about the quality of surgical care in Belgium ? Why and how Opening
lecture of the 5th Belgian Surgical Week.
PMID- 28417718
TI - Occurrence of pancreatic, biliary tract, and gallbladder cancers in Alaska Native
people, 1973-2007.
AB - OBJECTIVES: To describe the occurrence of pancreatic, biliary tract, and
gallbladder cancers within the Alaska Native (AN) population. STUDY DESIGN:
Population-based analysis utilizing a tumor registry and comparative population
data. METHODS: Pancreaticobiliary cancers rates for AN people during 1973-2007
were determined from the Surveillance, Epidemiology, and End Results (SEER) AN
Tumor Registry. Cancer incidence rates were age-adjusted to the World Standard
Million and compared over 2 time periods with US white and black rates. RESULTS:
During 1973-2007, 213 AN people developed pancreatic cancer, 73 gallbladder
cancer and 61 biliary tract cancer. Pancreatic cancer occurs at similar rates in
AN men and women, but data for 1993-2007 indicate that the rates among AN men may
be increasing. The incidence rate in AN women (9.5/100,000) was statistically
higher than in US white women (5.8/100,000). The incidence for biliary tract
cancer in AN men and gallbladder cancer in AN men and women is statistically
higher than that for US whites and blacks. CONCLUSIONS: Pancreaticobiliary
cancers, particularly biliary tract and gallbladder cancers, in both AN men and
women and pancreatic cancer in women occur at an increased rate in AN people.
Risk factors relating to the elevated rate are discussed. Certain factors are
potentially modifiable, such as the use of tobacco and obesity.
PMID- 28417719
TI - Translational research to reduce trans-fat intakes in Northern Quebec (Nunavik)
Inuit communities: a success story?
AB - Following our results, based on population studies conducted in Greenland and
Northern Canada, that Nunavik Inuit were thrice as highly exposed to dietary
trans-fat as were Greenlandic Inuit, and that the biological levels found in
Nunavik were already associated with deleterious blood lipid profiles, we decided
to engage in translational activities. Our goal was to support Inuit communities
in the practical implementation of a reduction of the trans-fat content of food
sold in Nunavik. We carried out a preliminary feasibility study in Kuujjuaq and
participated in several meetings. This translational phase involved an Inuk
leader, an Inuk student, a southern student, a southern nutritionist and a
southern researcher in the framework of a public health project. In the present
article, we recount the different phases of the process, from research
implementation to results dissemination and institutional commitment to implement
a primary prevention program of reduction in trans-fat exposure in Nunavik. This
is the occasion to draw broader conclusions on the factors that could either act
in favour of or, on the contrary, would likely compromise the implementation of
primary prevention interventions dealing with food and nutrition in the Arctic.
Finally, we share some reflections on future translational activities dealing
with trans-fat as well as other junk food issues. The analytical framework we
propose integrates a range of factors, from geo-climatic to socio-economic, ethno
cultural, and even political, that we think should be examined while identifying
and building preventive recommendations and strategies related to the Northern
diet.
PMID- 28417720
TI - A longitudinal study of the effect of Antarctic residence on energy dynamics and
aerobic fitness.
AB - OBJECTIVES: To investigate the effect of Antarctic residence on energy dynamics
and aerobic fitness over the course of a year in over-wintering personnel. STUDY
DESIGN: A prospective longitudinal observational study. METHODS: A convenience
sample of personnel over-wintering at Rothera Research Station in Antarctica was
studied. Body weight, body fat, food intake, activity and aerobic fitness were
recorded every 30 days for 1 year. Body weight, body fat and food intake were
measured using weighing scales, skinfold callipers and diet records,
respectively; activity was measured using accelerometer-based activity trackers
and aerobic fitness using a treadmill protocol. Climate markers of temperature
and sunlight hours were also recorded. RESULTS: Twenty-one subjects took part in
the study over the 12-month period. A statistically significant increase in body
weight and body fat in winter was observed (p=0.012 and p=0.049, respectively).
There were no statistically significant trends in activity, food intake or
aerobic fitness. CONCLUSIONS: There were significant seasonal changes in body
weight and body fat, with both measures increasing in winter but no significant
changes in the other main outcome measures.
PMID- 28417721
TI - Physical activity and fitness in 8-year-old overweight and normal weight children
and their parents.
AB - OBJECTIVES: To compare the physical fitness and physical activity of 8-year-old
overweight children (n = 53) to normal weight children (n = 65), and to determine
whether a significant relationship exists between physical activity of parents
and their children. STUDY DESIGN: A cross-sectional study. METHODS: A total of
119 children from Northern Finland were recruited for the study. Waist
circumference, height, weight and BMI were measured. Physical activity of the
children and their parents was determined with self-administered 7-day recall
questionnaires (PAQ-C). Physical fitness of the children was evaluated with 7
items of the EUROFIT-test battery (flamingo balance test, plate tapping, sit-and
reach test, sit-ups, bent arm hang and 10*5 shuttle run). Aerobic capacity of the
children was tested with 6-minute walking test. RESULTS: Overweigh was related to
impaired performance in tests requiring muscle endurance, balance, explosive
power of lower extremities, upper body strength and endurance, speed and agility
in both genders and aerobic capacity in boys. Physical activity levels of
overweight boys (2.41 SD 0.72) were lower than their lean counterparts (2.91 SD
0.64, p = 0.004); no such difference was observed in girls (2.53 SD 0.64 vs. 2.59
SD 0.68, p = 0.741). Physical activity was significantly associated with better
performance in several physical fitness tests in boys, but not in girls. Mothers'
physical activity was associated with children's physical activity (r = 0.363, p
< 0.001), but no such association was found between fathers and children (r =
0.019, p = 0.864). CONCLUSION: This study shows an inverse relationship between
excess bodyweight and physical fitness in children. Mother-child relationship of
physical activity appeared to be stronger than father-child relationship.
Improving physical fitness in children through physical activity might require
interventions that are responsive to the ability and needs of overweight children
and their families and focus on helping parents and children to be physically
active together.
PMID- 28417723
TI - Re: Vitamin D deficiency among northern Native Peoples.
PMID- 28417722
TI - Health consumption in Sami speaking municipalities and a control group with
regard to medical imaging.
AB - OBJECTIVES: The Northern Norway Regional Health Authority trust aims to offer a
high quality specialist health care to all inhabitants. The objective of this
study was to document the consumption of medical imaging [conventional
radiography (CR), computerised tomography (CT), magnetic resonance (MR),
ultrasound (US)]. METHODS: The eight municipalities in northern Norway included
in the administration area of the Sami language law (Sami group - 132,490
persons/year in the period 2003-2009, mean/year 19,363 inhabitants) were matched
with a control group of 11 municipalities (non-Sami group - 135,539 persons/year,
mean/year 18,927 inhabitants). Population data was accessed from Statistics
Norway. Data on imaging exams were derived from a regional database including
production data from all public and private institutions within the region. All
four main modality groups (CR, CT, MR, US) were analysed. Variations for imaging
frequency on each modality were compared between the Sami and non-Sami
municipalities. RESULTS: A total of 278,832 exams were performed during study
period. The age adjusted exam rate (all modalities) was significantly higher (p <
0.001) in non-Sami (females and males) group. There was no difference with regard
to conventional radiography (CR) (p = 0.855). Whereas MR (p < 0.001) imaging was
more common in the Sami group, CT (p < 0.001) and US (p = 0.003) exams were more
frequently used in the control group. CONCLUSION: People living in Sami speaking
communities experienced significantly less CT and US exams, but had more MR exams
than the control group. A relatively high physical activity, obesity and a lower
risk of cancer may be explanations.
PMID- 28417724
TI - Factors related to fruit, vegetable and traditional food consumption which may
affect health among Alaska Native People in Western Alaska.
AB - OBJECTIVES: Determine intake of fruits, vegetables and traditional foods (TF),
availability of foods, and attitudes towards increasing their consumption. STUDY
DESIGN: Establish community baseline through a cross-sectional sample of
residents who were weighed, measured and interviewed. Village stores were
surveyed for food availability, price and quality. METHODS: Eighty-eight
respondents self-identified as the household member primarily responsible for
food shopping and cooking were surveyed in 3 Western Alaska Native villages using
a food frequency questionnaire, and village stores were evaluated using food
environment surveys. RESULTS: Overweight (BMI[kg/m2] > 25) was present in 68% of
participants. Fruit and vegetable intake (3.3 median servings/day) was low in
comparison to recommended intakes of 5-9 servings/d. Seventy-two per cent were
eating less than 5 servings/d of fruits and vegetables combined. Thirty-four per
cent of respondents were trying to eat more vegetables; 41% were trying to eat
more fruits. The median number of servings of TF was 3.2/d (mean 4.3/d). Seventy
seven per cent of respondents reported that they ate enough TF. CONCLUSION:
Recommendations to continue use of TF and increase intake of fruits and
vegetables are consistent with local attitudes. Our findings indicate that
increasing the availability of fruits and vegetables would be well received.
Information from this study provides a basis for nutrition education and food
supplement programs that is responsive to the needs and perceptions of the
residents. Continued TF intake and increased fruit and vegetable intake have the
potential to benefit the health of rural residents.
PMID- 28417725
TI - Traditional food consumption behaviour and concern with environmental
contaminants among Cree schoolchildren of the Mushkegowuk territory.
AB - OBJECTIVES: To investigate factors influencing consumption of traditional foods
(e.g. wild game, fish) and concerns about environmental contaminants among
schoolchildren of the Mushkegowuk Territory First Nations (Moose Factory, Fort
Albany, Kashechewan, Attawapiskat, and Peawanuck). STUDY DESIGN: Cross-sectional
data collection from a Web-based Eating Behaviour Questionnaire (WEB-Q). METHODS:
Schoolchildren in grades 6-12 (n = 262) responded to 4 of the WEB-Q questions:
(a) Do you eat game? (b) How often do you eat game? (c) How concerned are you
about the environmental contaminants in the wild game and fish that you eat? (d)
I would eat more game if... [6 response options]. Data were collected in 2004
(Fort Albany), 2005 (Peawanuck), 2006 (Attawapiskat), 2007 (Moose Factory) and
2009 (Kashechewan). Hierarchical log-linear modelling (LLM) was used for analyses
of multi-way frequency data. RESULTS: Of the schoolchildren answering the
specific questions: 174 consumed game; 95 reported concerns about contaminants in
game; and 84 would increase their game consumption if it were more available in
their homes. LLM revealed significant differences between communities;
schoolchildren in Moose Factory consumed game "rarely or never" at greater than
expected frequency, and fewer than expected consumed game "at least once a day".
Schoolchildren in Kashechewan had greater frequency of daily game consumption and
few were concerned about contaminants in game. Using LLM, we found that sex was
an insignificant variable and did not affect game consumption frequency or
environmental contaminant concern. CONCLUSION: The consumption of traditional
foods differed between communities and appears to be related to contamination
concerns. In addition, latitudinal variation appears to influence the frequency
of traditional food consumption in children; children in the most southerly
location consumed traditional food less frequently.
PMID- 28417726
TI - Heart rate is associated with markers of fatty acid desaturation: the GOCADAN
study.
AB - OBJECTIVES: To determine if heart rate (HR) is associated with desaturation
indexes as HR is associated with arrhythmia and sudden death. STUDY DESIGN: A
community based cross-sectional study of 1214 Alaskan Inuit. METHODS: Data of FA
concentrations from plasma and red blood cell membranes from those >=35 years of
age (n = 819) were compared to basal HR at the time of examination. Multiple
linear regression with backward stepwise selection was employed to analyze the
effect of the desaturase indexes on HR, after adjustment for relevant covariates.
RESULTS: The Delta5 desaturase index (Delta5-DI) measured in serum has recently
been associated with a protective role for cardiovascular disease. This index
measured here in plasma and red blood cells showed a negative correlation with
HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to be
related to cardiovascular disease (CVD) mortality, on the other hand, was
positively associated with HR, while the Delta6 desaturase index (Delta6-DI) had
no significant effect on HR. CONCLUSION: Endogenous FA desaturation is associated
with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden
death, which would at least partially explain the previously observed association
between cardiovascular mortality and desaturase activity.
PMID- 28417727
TI - Metabolic profile in two physically active Inuit groups consuming either a
western or a traditional Inuit diet.
AB - OBJECTIVES: To evaluate the effect of regular physical activity on metabolic risk
factors and blood pressure in Inuit with high BMI consuming a western diet (high
amount of saturated fatty acids and carbohydrates with a high glycemic index).
STUDY DESIGN: Cross sectional study, comparing Inuit eating a western diet with
Inuit eating a traditional diet. METHODS: Two physically active Greenland Inuit
groups consuming different diet, 20 eating a traditional diet (Qaanaaq) and 15
eating a western diet (TAB), age (mean (range)); 38, (22-58) yrs, BMI; 28 (20-40)
were subjected to an oral glucose tolerance test (OGTT), blood sampling, maximal
oxygen uptake test, food interview/collection and monitoring of physical
activity. RESULTS: All Inuit had a normal OGTT. Fasting glucose (mmol/l), HbA1c
(%), total cholesterol (mmol/l) and HDL-C (mmol/l) were for Qaanaaq women: 4.8+/
0.2, 5.3+/-0.1, 4.96+/-0.42, 1.34+/-0.06, for Qaanaaq men: 4.9+/-0.1, 5.7+/-0.1,
5.08+/-0.31, 1.28+/-0.09, for TAB women: 5.1+/-0.2, 5.3+/-0.1, 6.22+/-0.39,
1.86+/-0.13, for TAB men: 5.1+/-0.2, 5.3+/-0.1, 6.23+/-0.15, 1.60+/-0.10. No
differences were found in systolic or diastolic blood pressure between the
groups. There was a more adverse distribution of small dense LDL-C particles and
higher total cholesterol and HDL-C concentration in the western diet group.
CONCLUSIONS: Diabetes or impaired glucose tolerance was not found in the Inuit
consuming either the western or the traditional diet, and this could, at least
partly, be due to the high amount of regular daily physical activity. However,
when considering the total cardio vascular risk profile the Inuit consuming a
western diet had a less healthy profile than the Inuit consuming a traditional
diet.
PMID- 28417728
TI - Frequent use of primary health care service in Greenland: an opportunity for
undiagnosed disease case-finding.
AB - OBJECTIVES: To estimate the age- and gender-specific consultation rates of
patients who availed primary health care service in Greenland and to analyse
contact patterns among patients in Nuuk. DESIGN: Observational and cross
sectional register study using data captured from the medical records. MATERIALS
AND METHODS: The number of patients specified by age and gender who had contacted
the primary health care centres within the last year was identified using a
statistic module applied to the electronic medical records system. The population
as it was on the 1st of January 2011 was used as the background population. The
age- and gender-specific consultation rates were calculated. Review of most
recent contact was performed in a subsample of patients from Nuuk, and
information of the type of contact and diagnoses was obtained. RESULTS: Eighty
three percent of the population in Greenland had been in contact with the primary
health care centre within the last year. Females were more frequent users than
males. A subsample of 400 patients in Nuuk was identified. Personal contact was
the most frequent type of consultation (75.8%), followed by telephone (14.8%) and
e-mail (9.8%) consultations. Musculoskeletal symptoms accounted for the most
frequent bases for diagnoses. CONCLUSION: More than 80% of the whole population
has been in contact with the primary health care system within the last year.
This indicates that opportunistic case-finding of chronic diseases such as
diabetes, hypertension, etc. providing a possible strategy for decreasing the
number of undiagnosed cases.
PMID- 28417729
TI - Preterm birth in the Inuit and First Nations populations of Quebec, Canada, 1981
2008.
AB - OBJECTIVES: To evaluate preterm birth (PTB) for Inuit and First Nations vs. non
Indigenous populations in the province of Quebec, Canada. STUDY DESIGN:
Retrospective cohort study. METHODS: We evaluated singleton live births for
Quebec residents, 1981-2008 (n = 2,310,466). Municipality of residence (Inuit
inhabited, First Nations-inhabited, rest of Quebec) and language (Inuit, First
Nations, French/English) were used to identify Inuit and First Nations births.
The outcome was PTB (<37 completed weeks). Cox proportional hazards regression
was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) of
PTB, adjusting for maternal age, education, marital status, parity and birth
year. RESULTS: PTB rates were higher for Inuit language speakers in Inuit
inhabited areas and the rest of Quebec compared with French/English speakers in
the rest of Quebec, and disparities persisted over time. Relative to
French/English speakers in the rest of Quebec, Inuit language speakers in the
rest of Quebec had the highest risk of PTB (HR 1.98, 95% CI: 1.62-2.41). The risk
was also elevated for Inuit language speakers in Inuit-inhabited areas, though to
a lesser extent (HR 1.29, 95% CI: 1.18-1.41). In contrast, First Nations language
speakers in First Nations-inhabited areas and the rest of Quebec had similar or
lower risks of PTB relative to French/English speakers in the rest of Quebec.
CONCLUSIONS: Inuit populations, especially those outside Inuit-inhabited areas,
have persistently elevated risks of PTB, indicating a need for strategies to
prevent PTB in this population.
PMID- 28417730
TI - From science to action and from action to science: the Nunavik Trichinellosis
Prevention Program.
AB - OBJECTIVES: During the 1980s, walrus-meat consumption caused infections with the
parasite Trichinella nativa in Nunavik inhabitants. In response to these events,
stakeholders set up the community-based Nunavik Trichinellosis Prevention Program
(NTPP). The objectives of the present communication are to review the NTPP,
describe how science and action were interwoven in its development and identify
its assets and limitations. STUDY DESIGN: Descriptive study. METHODS: The NTPP
relies on a pooled digestion assay of tongue samples taken from each harvested
walrus. The public health recommendations depend on the results of the analyses:
infected walrus meat should be destroyed; parasite-free meat may be eaten raw or
cooked. RESULTS: All communities involved in the walrus hunt participate in the
NTPP and a high percentage of harvested walruses are included in the NTPP.
Infected animals account for 2.9% of the walruses tested (20/694) since 1992. The
NTPP permitted the early management of a trichinellosis event in 1997. Since
then, it prevented the new occurrence of outbreaks related to walruses hunted by
Nunavimmiut. CONCLUSIONS: The absence of recent major outbreaks of trichinellosis
in Nunavik may reasonably be attributed to the NTPP. The success of the program
stands on many facilitating factors such as the nature of the disease and its
source, the existence of an efficient analytic method, the strong involvement of
the different partners including direct resource users, as well as the
comprehensive bidirectional science-to-action approach that has been followed.
PMID- 28417731
TI - Dietary quality and adequacy among Aboriginal alcohol consumers in the Northwest
Territories, Canada.
AB - OBJECTIVES: The present study aimed to assess dietary adequacy and quality among
Inuvialuit alcohol consumers and non-consumers in the Northwest Territories
(NWT), Canada. STUDY DESIGN: Cross-sectional study. METHODS: A validated
quantitative food frequency questionnaire was administered to individuals (n =
216) of randomly selected households in 3 NWT communities to capture dietary
intake and alcohol consumption over a 30-day recall period. The daily energy and
nutrient intake, dietary adequacy and the top food sources of energy and selected
nutrients were determined by alcohol consumption status. RESULTS: Energy intake
was higher among all alcohol consumers regardless of gender. Male alcohol
consumers had lower nutrient intake density (per 4,184 kJ) of protein,
cholesterol and several micronutrients (p <= 0.05), and female alcohol consumers
had lower intake density of saturated fat (p <= 0.01), thiamine, folate and
sodium (p <= 0.05). Among all men and women, 70-100% had inadequate intakes of
dietary fibre, vitamin E and potassium. Non-nutrient-dense foods contributed
similar amounts and traditional foods (TF) contributed 3% less to energy
comparing alcohol consumers to non-consumers. CONCLUSION: Nutrient inadequacies
are prevalent among Aboriginal populations in the Canadian Arctic and may be
exacerbated by alcohol consumption due to alcohol's effects on dietary intake,
nutrient transport and metabolism. Adult Inuvialuit who consumed alcohol had
increased caloric intake and consumed similar amounts of non-nutrient-dense foods
and less nutrient-dense TF. Fewer dietary inadequacies were observed among
alcohol consumers than non-consumers, which might be due to the increase in
overall food intake among alcohol consumers; however, further exploration of
volume and pattern of drinking might help explain this result.
PMID- 28417732
TI - Climate change and zoonotic infections in the Russian Arctic.
AB - Climate change in the Russian Arctic is more pronounced than in any other part of
the country. Between 1955 and 2000, the annual average air temperature in the
Russian North increased by 1.2 degrees C. During the same period, the mean
temperature of upper layer of permafrost increased by 3 degrees C. Climate change
in Russian Arctic increases the risks of the emergence of zoonotic infectious
diseases. This review presents data on morbidity rates among people, domestic
animals and wildlife in the Russian Arctic, focusing on the potential climate
related emergence of such diseases as tick-borne encephalitis, tularemia,
brucellosis, leptospirosis, rabies, and anthrax.
PMID- 28417733
TI - Dietary recommendations regarding pilot whale meat and blubber in the Faroe
Islands.
AB - For centuries the pilot whale has been an important part Faroese life - both in
regard to food and culture. However, studies dating back to 1977 have shown an
increase in contamination of the meat, blubber, liver and kidneys of pilot
whales. Several birth cohorts have been established in the Faroes in order to
discover the health effects related to mercury and organchlorine exposure. In
short the results have so far shown that: mercury from pilot whale meat adversely
affects the foetal development of the nervous system; the mercury effect is still
detectable during adolescence; the mercury from the maternal diet affects the
blood pressure of the children; the contaminants of the blubber adversely affect
the immune system so that the children react more poorly to immunizations;
contaminants in pilot whales appear to increase the risk of developing
Parkinson's disease in those who often eat pilot whale; the risk of hypertension
and arteriosclerosis of the carotid arteries is increased in adults who have an
increased exposure to mercury; septuagenarians with type 2 diabetes or impaired
fasting glycaemia tended to have higher PCB concentrations and higher past intake
of traditional foods, especially during childhood and adolescence. Also impaired
insulin secretion appears to constitute an important part of the type 2 diabetes
pathogenesis associated with exposure to persistent lipophilic food contaminants.
From the latest research results, the authors consider that the conclusion from a
human health perspective must be to recommend that pilot whale is no longer used
for human consumption.
PMID- 28417734
TI - Dietary exposure to persistent organic pollutants and metals among Inuit and
Chukchi in Russian Arctic Chukotka.
AB - OBJECTIVES: The general aim was to assess dietary exposure to selected persistent
organic pollutants (POPs) and metals among Eskimo (Inuit) and Chukchi of the
Chukotka Peninsula of the Russian Arctic, and to establish recommendations for
exposure risk reduction. STUDY DESIGN: A cross-sectional evaluation of
nutritional patterns of coastal and inland indigenous peoples of the Chukotka
Autonomous Okrug (in 2001-2003); assessment of the levels of persistent toxic
substances (PTSs) in traditional foods and their comparison to Russian food
safety limits; the identification of local sources of food contamination; and the
recommendation and implementation of risk management measures. METHODS: Community
based dietary survey of self reported food frequencies (453 persons), chemical
analyses (POPs and metals) of local foods and indoor matters (397 samples),
substantiation of recommendations for daily (weekly, monthly) intakes of
traditional food. RESULTS: POPs in traditional food items are generally below the
Russian food safety limits except marine mammal fat, while Hg and Cd are high
mainly in mammal viscera. Lead is relatively low in tissues of all animals
studied. For the Chukotka coastal communities, seals constitute the principal
source of the whole suite of PTSs considered. Consumption restrictions are
recommended for marine and freshwater fish, some wild meats (waterfowl and seal),
fats (whale and seal), liver (most animals) and kidney (reindeer, walrus and
seal). Evidence is presented that contamination of foodstuffs may be
significantly increased during storing/processing/cooking of food due to indoor
and outdoor environmental conditions. CONCLUSIONS: Based on the analytical
findings and the local PTSs sources identified, guidelines on food safety are
suggested, as well as measures to reduce food contamination and domestic and
local sources. Important and urgent remedial actions are recommended to minimize
PTSs environmental and domestic contamination. Waste clean-up activities started
in coastal Chukotka in 2007.
PMID- 28417735
TI - Lead exposure in Nunavik: from research to action.
AB - BACKGROUND: In 1999, the Government of Canada regulated the use of lead shot for
hunting. Concurrently, the Nunavik Regional Board of Health and Social Services
(NRBHSS) was informed of the results of an isotope study that pointed to lead
ammunition as a likely source of lead exposure in Nunavik. Rapidly thereafter, a
coalition for the banning of lead shot was implemented by the NRBHSS as well as
by regional/local partners and by Inuit hunters in order to disseminate this
information to the public. OBJECTIVES: The purpose of this article is to describe
the intervention conducted in the winter of 1999 by the NRBHSS and to assess the
combined impact of national legislation and an awareness campaign on blood lead
levels in Nunavik. STUDY DESIGN: Impact assessment of the intervention for the
banning of lead shot conducted in 1999 in Nunavik using blood lead levels data
before and after the intervention. METHODS: Data on blood lead levels in Nunavik
describing foetal exposure as well as during childhood and in adults published
between 1992 and 2009 were compiled. Blood lead levels in Nunavik prior to and
after the interventions were compared. To assess the current situation, the most
recent blood lead levels were compared with those from surveys conducted during
the same period in North America. RESULTS: Analysis of blood samples collected
from umbilical cord and from adults show that blood lead levels in Nunavik
significantly declined between 1992 and 2004. Nevertheless, lead exposure in
Nunavik still remains higher in comparison to that observed in other North
American surveys. CONCLUSIONS: The current situation regarding lead exposure in
Nunavik has significantly improved as a result of the implemented intervention.
However, according to recent data, a gap still subsists relative to other North
American populations.
PMID- 28417736
TI - The role of Indigenous knowledge in environmental health risk management in
Yukon, Canada.
AB - OBJECTIVES: This project aimed to gain better understandings of northern
Indigenous risk perception related to food safety and to identify the role that
Indigenous knowledge (IK) plays in risk management processes to support more
effective and culturally relevant benefit-risk (B-R) management strategies. STUDY
DESIGN: The project used an exploratory qualitative case study design to
investigate the role and place of IK in the management of environmental
contaminants exposure via consumption of traditional foods in Yukon First Nations
(YFNs). METHODS: Forty-one semi-directive interviews with Traditional Food
Knowledge Holders and Health and Environment Decision-makers were conducted. A
review and analysis of organizational documents related to past risk management
events for the issue was conducted. Thematic content analysis was used to analyze
transcripts and documents for key themes related to the research question.
RESULTS: There was a recognized need by all participants for better collaboration
between scientists and YFN communities. YFNs have been involved in identifying
and defining community concerns about past risk issues, setting a local context,
and participating in communications strategies. Interviewees stressed the need to
commit adequate time for building relationships, physically being in the
community, and facilitating open communication. Conducting community-based
projects was identified as critical for collaboration and for cooperative
learning and management of these issues. CONCLUSIONS: The perception of
"effective" benefit-risk management is significantly influenced by the efforts
made to include local communities in the process. A set of common guiding
principles within a process that brings together people and knowledge systems may
provide a more effective way forward in cross-cultural, multiple knowledge system
contexts for complex benefit-risk issues than a prescriptive rigid framework.
PMID- 28417737
TI - A Wellness Course for Community Health Workers in Alaska: "wellness lives in the
heart of the community".
AB - OBJECTIVES: To develop, implement, and evaluate a culturally respectful Wellness
Course with and for Alaska's village-based Community Health Workers (CHWs) to
support community health promotion and disease prevention. STUDY DESIGN: This
article describes Wellness Course development, implementation, and evaluation.
METHODS: Five 5-day Wellness Courses were provided for 55 CHWs from communities
throughout Alaska. Fifty-two of 55 participants completed a post-course written
evaluation. Post-course telephone interviews were conducted with participants
(11/32) from the first 3 courses. RESULTS: On written post-course evaluations,
all participants wrote detailed descriptions of what they learned and 98% (51/52)
felt more confident in their knowledge and ability to present community wellness
information. As a result of course participation, 88% (46/52) of CHWs wrote ways
they would support family and community wellness, and 85% (44/52) wrote ways they
planned to take better care of their health. During the in-depth post-course
interviews, all 11 CHWs interviewed described ways the Wellness Course increased
their health knowledge, helped them in their work, and prepared them to
effectively engage with their communities to promote health. CONCLUSIONS:
Learning wellness information with hands-on activities and practising health
presentation and community engagement skills within the course design increased
participants' wellness knowledge and skills, confidence, and motivation to
provide community wellness activities. Techniques for active listening, engaging
community, and using the arts and storytelling as culturally respectful health
promotion are tools that when used by CHWs within their own community have
potential to empower community wellness.
PMID- 28417738
TI - Survival of Sami cancer patients.
AB - OBJECTIVES: The incidence of cancer among the indigenous Sami people of Northern
Finland is lower than among the Finnish general population. The survival of Sami
cancer patients is not known, and therefore it is the object of this study. STUDY
DESIGN: The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31
December 1978 in the two Sami municipalities of Inari and Utsjoki, which are
located in Northern Finland and are 300-500 km away from the nearest central
hospital. The survival experience of Sami and non-Sami cancer patients diagnosed
in this cohort during 1979-2009 was compared with that of the Finnish patients
outside the cohort. METHODS: The Sami and non-Sami cancer patients were matched
to other Finnish cancer patients for gender, age and year of diagnosis and for
the site of cancer. An additional matching was done for the stage at diagnosis.
Cancer-specific survival analyses were made using the Kaplan-Meier method and Cox
regression modelling. RESULTS: There were 204 Sami and 391 non-Sami cancer cases
in the cohort, 20,181 matched controls without matching with stage, and 7,874
stage-matched controls. In the cancer-specific analysis without stage variable,
the hazard ratio for Sami was 1.05 (95% confidence interval 0.85-1.30) and for
non-Sami 1.02 (0.86-1.20), indicating no difference between the survival of those
groups and other patients in Finland. Likewise, when the same was done by also
matching the stage, there was no difference in cancer survival. CONCLUSION: Long
distances to medical care or Sami ethnicity have no influence on the cancer
patient survival in Northern Finland.
PMID- 28417739
TI - Snow crab allergy and asthma among Greenlandic workers - a pilot study.
AB - OBJECTIVES: To study snow crab sensitization, occupational allergy and asthma in
the snow crab industry in Greenland, as high rates have been found in Canada, but
no reports have emerged from the same industry in Greenland. STUDY DESIGN: Pilot
survey. METHODS: Twenty workers (19 of Inuit and 1 of other origin) in a snow
crab (Chionoecetes opilio) and Atlantic shrimp (Pandalus borealis) processing
plant in Greenland were assessed with skin prick tests (SPTs) with common
aeroallergens and specific allergens from snow crab and shrimp extracts,
spirometry, blood sampling for total IgE and specific IgE determination. Eighteen
workers contributed a questionnaire-based medical interview. RESULTS: Positive
skin prick test reactions were common to snow crab (40%) and shrimp (20%).
Specific IgE to snow crab were positive in 4 workers (21%). Two workers had
elevated total IgE levels. Symptoms suggestive of asthma were common (45%). Work
related symptoms of skin rash, rhinitis, and/or conjunctivitis were reported by
50%, and symptoms from the lower airways by 39%. Combining history of work
related symptoms with results from specific SPTs and/or specific IgE
determination suggested that 11 and 22% of workers suffered from probable and
possible occupational asthma, respectively, whereas 22% had possible occupational
dermatitis or rhinitis. CONCLUSIONS: Greenlander Inuit do not appear to be
protected against sensitization to snow crab or shrimp when occupationally
exposed to these. This pilot study suggests that occupational allergy and asthma
may be as common a problem in Greenlandic workers as in Canadian.
PMID- 28417740
TI - Living conditions, quality of life, adherence and treatment outcome in
Greenlandic HIV patients.
AB - OBJECTIVES: Despite a high level of sexually transmitted infections, HIV
incidence has remained quite stable in Greenland with 5-6 new cases per year
(approximately 10 per 100,000). However, disease control is suboptimal and
mortality is relatively high. The aim of the present study was to determine
associations between adherence to treatment and treatment outcome, living
conditions and quality of life among HIV patients in Greenland. MATERIAL AND
METHODS: Cross-sectional questionnaire-based cohort study of HIV patients in
Greenland during 2008-2009. Data regarding treatment, viral load, CD4 count, etc.
were obtained from a central HIV-database. RESULTS: Forty-six persons, 17 women
and 29 men, of the 60 registered HIV-positive patients (77%) were included.
Eighty percent were heterosexually infected and 17% by men having sex with men
(MSM) activity. Median age at the time of diagnosis was 48 years (range 20-63).
Eighty-nine percent received highly active antiretroviral therapy (HAART). Sixty
seven percent were adherent as defined by a combination of adherence to
appointments and to treatment. Ninety-seven percent of adherent and 17% non
adherent patients on HAART had HIV-RNA less than 200 copies per ml (RR=24.2,
p<0.0001). Poor adherence was associated with younger age (<50 years) (adjusted
RR=7.95, p=0.005) and living in remote areas with no direct contact with skilled
personnel (adjusted RR=6.75, p=0.01). Unsafe sex was also more frequent among non
adherent patients (RR=4.12, p=0.026), but due to few answers this topic was not
included in the multivariate model. CONCLUSION: The HIV population in Greenland
is peculiar since most patients are heterosexually infected and middle-aged at
diagnosis. A relatively poor adherence and consequently inferior treatment
outcome is related to young age and living in remote areas.
PMID- 28417741
TI - Bachelor studies for nurses organised in rural contexts - a tool for improving
the health care services in circumpolar region?
AB - OBJECTIVES: This article is based on a pilot study of Finnmark University
College's off-campus bachelor programme (BA) for nurses, organised in rural
areas. The objectives were to explore whether these courses had contributed to
reduced vacancies; whether the learning outcome of the off-campus courses was the
same as the on-campus programme, and how the education had influenced the nurses'
professional practice in local health services. STUDY DESIGN: In the study we
used mixed strategies in data collection and analyses. METHODS: Data about course
completion, average age, average grades and retention effect were collected in
2009/2010 from 3 off-campus classes and their contemporary on-campus classes.
Then 7 of the off-campus nurses were interviewed. A content analytical approach
to the data was employed. RESULTS: With retention of 93%, the off-campus BA
course for nurses has been one of the most effective measures, particularly in
rural areas. The employers' support for further education after graduating seems
to be an important factor for the high retention rate. Teaching methods such as
learning activities in small local groups influenced the nurses' professional
development. Local training grants, supervision and a local learning environment
were important for where they chose their first job after graduation.
CONCLUSIONS: The study confirms that nurses educated through off-campus courses
remain in the county over time after graduating. The "home-grown" nurses are
familiar with the local culture and specific needs of the population in this
remote area. The study confirms findings in other studies, that further education
is an important factor for nurses' retention.
PMID- 28417742
TI - Socioeconomic characteristics and health outcomes in Sami speaking municipalities
and a control group in northern Norway.
AB - OBJECTIVES: The Sami people constitute an ethnic minority in northern Norway. The
objectives of this study were to compare municipalities with a majority of Sami
in the population and a control group with regard to socioeconomic factors and
health outcome. METHODS: Original data from Statistics Norway and Directorate of
health on socioeconomic factors (education, unemployment, disability, poverty)
and health outcomes [total mortality, cancer specific mortality, cardiovascular
disease (CVD) specific mortality] were imported from the "Health Atlas" at the
Northern Norway Regional Health Authority (NNRHA) trust. The 8 municipalities in
the administration area of the Sami language law (Sami-majority group - 18,868
inhabitants) was compared with a control group consisting of 11 municipalities
where the Sami constitute a small minority in the population (18,931
inhabitants). Most data were from 2005 and 2008. RESULTS: There was no
significant difference in socioeconomic factors. Overall, cancer- and CVD
specific mortality rates were similar in both groups. The life expectancy was
significantly longer among women in the Sami-majority area (81.3 vs. 79.5 years,
p=0.035) and males (74.5 vs. 72.0 years, p=0.037). CONCLUSION: Socioeconomic
factors and cause-specific mortality rate were similar in the Sami-majority group
and the control group. Residents of both sexes in Sami-majority areas enjoyed
longer life expectancy.
PMID- 28417743
TI - Coming of age: how young women in the Northwest Territories understand the
barriers and facilitators to positive, empowered, and safer sexual health.
AB - OBJECTIVES: Compared to other young Canadians, youth in the Northwest Territories
(NWT) suffer disproportionately from negative sexual health outcomes, including
high rates of sexually transmitted infections and unintended pregnancies. This
study aimed to identify the self-perceived barriers and facilitators to positive,
empowered, and safer sexual health that impact female youth in the NWT. STUDY
DESIGN AND METHODS: A total of 12 females aged 15-19 who live in the NWT were
recruited through purposive sampling to participate in semi-structured, face-to
face interviews. Inductive coding and thematic analysis of transcribed data
occurred using Atlas.ti. RESULTS: Overall 4 main themes influenced the sexual
health of these women: sexual health knowledge, relationships with the self and
others, access to quality sexual health resources, and alcohol use/abuse.
CONCLUSION: Recommendations for future action include improving the content and
delivery of sexual health education, enhancing parent-adolescent sexual health
communication, providing workshops to empower young women to assert themselves
within relationships, and supporting an environment that normalizes youth
sexuality.
PMID- 28417744
TI - Higher body mass, older age and higher monounsaturated fatty acids intake reflect
better quantitative ultrasound parameters in Inuit preschoolers.
AB - OBJECTIVES: Investigate the effects of selected factors associated with
quantitative ultrasound parameters among Inuit preschoolers living in Arctic
communities (56 degrees 32'-72 degrees 40'N). MATERIALS AND METHODS: Children
were selected randomly in summer and early fall (n=296). Dietary intake was
assessed through the administration of a 24-h dietary recall (24-h recall) and a
food frequency questionnaire (FFQ). Anthropometry was measured using standardized
procedures. Plasma 25-hydroxy vitamin D (25(OH)D) and parathyroid hormone (PTH)
were measured using a chemiluminescent assay (Liaison, Diasorin). Quantitative
ultrasound parameters were measured using Sahara Sonometer, (Hologic Inc.).
RESULTS: Children divided by speed of sound (SoS) and broadband ultrasound
attenuation (BUA) quartiles were not different for age (years), sex (M/F),
calcium (mg/d) and vitamin D intake (ug/d) and plasma 25(OH)D concentration
(nmol/L). However, children in the highest BUA and SoS quartile had higher body
mass index (BMI) compared to those in quartile 1. Using multivariate linear
regression, higher BMI, older age and monounsaturated fatty acids (MUFA) intake
were predictors of BUA while only BMI was a predictor of SoS. CONCLUSIONS:
Further investigation assessing intakes of traditional foods (TF) and nutrients
affecting bone parameters along with assessment of vitamin D status of Inuit
children across seasons is required.
PMID- 28417745
TI - Level of selected nutrients in meat, liver, tallow and bone marrow from semi
domesticated reindeer (Rangifer t. tarandus L.).
AB - OBJECTIVES: To acquire new knowledge on the nutritional composition of semi
domesticated reindeer (Rangifer t. tarandus L.) and their nutritional value for
humans. The results could be useful in updating the Norwegian Food Composition
Database, whose current data on reindeer is limited. STUDY DESIGN: Cross
sectional study on population of semi-domesticated reindeer from 2 northern
Norwegian counties (Finnmark and Nordland). METHODS: Semi-domesticated reindeer
carcasses (n=31) were randomly selected, from which meat, liver, tallow and bone
marrow samples were collected. Selected vitamins, minerals, fatty acids and total
lipids were studied. RESULTS: As expected, reindeer meat was found to be lean (2%
total lipid), thus it is a good source of low-fat meat. The meat was also found
to be a good source of vitamin B12, docosapentaenoic acid (C22:5 n-3) and alpha
linolenic acid (C18:3 n-3). Statistically significant differences (p<0.05) in
most of the nutrient levels between meat and the rest of the studied reindeer
tissues were observed. In most cases, the liver, tallow and bone marrow had
higher nutritional values when compared to meat. Liver had the highest
concentrations of vitamin A, all vitamin B types, vitamin C, iron, selenium and
the total amount of polyunsaturated fatty acids (n-3). Additionally, liver was
the only edible tissue that contained vita-mins B9 and C. The vast majority of
the vitamin concentrations in liver, tallow and bone marrow were significantly
correlated with the concentrations in meat (p<0.05). CONCLUSIONS: The studied
tissues from reindeer demonstrated that reindeer is a valuable food source that
could meet or contribute to the consumers' nutritional recommended daily
allowance (RDA). 1Published 'ahead-of-print' 8 November 2011 (at www.ijch.fi ) in
accordance with previous publisher's routines.
PMID- 28417746
TI - Mammographic screening in Sami speaking municipalities and a control group. Are
early outcome measures influenced by ethnicity?
AB - Objectives . Female citizens of Sami (the indigenous people of Norway)
municipalities in northern Norway have a low risk of breast cancer. The objective
of this study was to describe the attendance rate and outcome of the Norwegian
Breast Cancer Screening Program (NBCSP) in the Sami-speaking municipalities and a
control group. Study design . A retrospective registry-based study. Methods . The
8 municipalities included in the administration area of the Sami language law
(Sami) were matched with a control group of 11 municipalities (non-Sami).
Population data were accessed from Statistics Norway. Data regarding invitations
and outcome in the NBCSP during the period 2001-2010 was derived from the Cancer
Registry of Norway (CRN). The NBCSP targets women aged 50-69 years. Rates and
percentages were compared using chi-square test with a p-value<0.05 as
statistical significant. Results . The attendance rate in the NBCSP was 78% in
the Sami and 75% in the non-Sami population (p< 0.01). The recall rates were 2.4
and 3.3% in the Sami and non-Sami population, respectively (p<0.01). The rate of
invasive screen detected cancer was not significantly lower in the Sami group
(p=0.14). The percentage of all breast cancers detected in the NBCSP among the
Sami (67%) was lower compared with the non-Sami population (86%, p=0.06).
Conclusion . Despite a lower risk of breast cancer, the Sami attended the NBCSP
more frequently than the control group. The recall and cancer detection rate was
lower among the Sami compared with the non-Sami group.
PMID- 28417748
TI - Demographic and contextual factors associated with inhalant use among youth in
rural Alaska.
AB - BACKGROUND: Abuse of harmful legal products that can be inhaled or ingested is a
serious and growing problem in many rural Alaskan communities, and particularly
so among preteens. METHODS: This study analyses data collected during baseline
measurements of a 5-year NIH/NIDA-funded study entitled A Community Trial to
Prevent Youth's Abuse of Harmful Legal Products in Alaska. Youth in 8 communities
located throughout the state participated in a survey during the fall of 2009 to
measure the prevalence and availability of harmful legal products (n=697). The
goal of the analysis presented here is to compare the contextual factors of
inhalant users and non-users in rural Alaskan communities. RESULTS: As reported
in national surveys of substance use among youth, participants in this study
indicated using alcohol more than any other substance. Inhalants were the second
most common substance abused, higher than either cigarettes or marijuana.
Lifetime use varied among demographic factors such as age, gender and ethnicity
as well as contextual factors including academic performance, parent employment,
household living situation and income. When compared to non-users, significantly
larger proportions of participants reporting lifetime inhalant use indicated easy
availability of inhalants in their home, school and retail outlets. Users were
also significantly more likely than non-users to have consumed alcohol.
CONCLUSION: Results of this study may inform the development of effective
interventions in other rural communities.
PMID- 28417749
TI - Traditional food consumption is associated with higher nutrient intakes in Inuit
children attending childcare centres in Nunavik.
AB - OBJECTIVES: To describe traditional food (TF) consumption and to evaluate its
impact on nutrient intakes of preschool Inuit children from Nunavik. DESIGN: A
cross-sectional study. METHODS: Dietary intakes of children were assessed with a
single 24-hour recall (n=217). TF consumption at home and at the childcare
centres was compared. Differences in children's nutrient intakes when consuming
or not consuming at least 1 TF item were examined using ANCOVA. RESULTS: A total
of 245 children attending childcare centres in 10 communities of Nunavik were
recruited between 2006 and 2010. The children's mean age was 25.0+/-9.6 months
(11-54 months). Thirty-six percent of children had consumed at least 1 TF item on
the day of the recall. TF contributed to 2.6% of total energy intake. Caribou and
Arctic char were the most reported TF species. Land animals and fish/shellfish
were the main contributors to energy intake from TF (38 and 33%, respectively).
In spite of a low TF intake, children who consumed TF had significantly (p<0.05)
higher intakes of protein, omega-3 fatty acids, iron, phosphorus, zinc, copper,
selenium, niacin, pantothenic acid, riboflavin, and vitamin B12, and lower
intakes of energy and carbohydrate compared with non-consumers. There was no
significant difference in any of the socio-economic variables between children
who consumed TF and those who did not. CONCLUSION: Although TF was not eaten
much, it contributed significantly to the nutrient intakes of children.
Consumption of TF should be encouraged as it provides many nutritional, economic,
and sociocultural benefits.
PMID- 28417750
TI - Modern contact investigation methods for enhancing tuberculosis control in
Aboriginal communities.
AB - The Aboriginal communities in Canada are challenged by a disproportionate burden
of TB infection and disease. Contact investigation (CI) guidelines exist but
these strategies do not take into account the unique social structure of
different populations. Because of the limitations of traditional CI, new
approaches are under investigation and include the use of social network
analysis, geographic information systems and genomics, in addition to the
widespread use of genotyping to better understand TB transmission. Guidelines for
the routine use of network methods and other novel methodologies for TB CI and
outbreak investigation do not exist despite the gathering evidence that these
approaches can positively impact TB control efforts, even in Aboriginal
communities. The feasibility and efficacy of these novel approaches to CI in
Aboriginal communities requires further investigation. The successful integration
of these novel methodologies will require community involvement, capacity
building and ongoing support at every level. The outcome will not only be the
systematic collection, analysis, and interpretation of CI data in high-burden
communities to assess transmission but the prioritization of contacts who are
candidates for treatment of LTBI which will break the cycle of transmission.
Ultimately, the measure of success will be a clear and sustained decline in TB
incidence in Aboriginal communities.
PMID- 28417751
TI - Incidence of pancreatic cancer in Greenland 2000-2010.
AB - BACKGROUND: Inuit people are known to be at an increased risk of cancers usually
uncommon to the western world such as cancers of the nasopharynx and salivary
glands. But what is the trend regarding pancreatic cancer? OBJECTIVE: To
determine the incidence of pancreatic cancer (PC) in Greenland compared with
Denmark in the period 2000-2010. STUDY DESIGN: Retrospective register-based
study. Cases were retrieved from The Danish Cancer Register and The Greenlandic
Patient Register and stratified in 5-year age intervals for each year. Age
standardized incidence ratios (SIR) for each year for Greenland compared with
Denmark were calculated using the number of cases and the number of inhabitants
in each 5-year age interval and in each country. The average SIR for the entire
period was calculated using a weighted average. RESULTS: The study revealed a SIR
of 2.38 (95% CI: 1.97-2.86; p<0.0001) indicating a significantly increased
incidence of PC in Greenland compared with Denmark. A linear regression analysis
showed no significant change in the SIR over time (p for trend 0.25) as well as
no significant change isolated in Greenland (p for trend 0.8). Furthermore, the
Inuit were significantly younger at the time of diagnosis (mean 62.7 vs. 70.0;
p<0.0001). CONCLUSIONS: The age-standardized incidence of PC is 138% higher in
Greenland than in Denmark. A part of this could be explained by a higher
prevalence of smoking and DM-2. However, the impact of genetic factors cannot be
disregarded and should be subjected to further investigation.
PMID- 28417752
TI - Treatment eligibility in Alaska Native and American Indian persons with hepatitis
C virus infection.
AB - OBJECTIVES: Treatment with pegylated interferon and ribavirin may prevent
progression of liver disease among patients with chronic hepatitis C virus
infection (HCV). Treatment initiation is based on published clinical eligibility
criteria, patients' willingness to undergo treatment and likelihood of success.
We examined treatment eligibility in a cohort of Alaska Native and American
Indian persons with chronic HCV infection. STUDY DESIGN: Retrospective cohort
study. METHODS: Medical records of all treatment naive HCV RNA positive patients
given an appointment by hepatology specialty clinic staff in 2003 and 2007 were
evaluated by a hepatology provider to investigate documented reasons for
treatment deferral. RESULTS: Treatment was initiated in 4 of 94 patients (4%) in
2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral
in 2003 versus 2007 included inconsistent appointment attendance (36% of
deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17%
vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled
psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%).
There was significant improvement in proportion of appointments attended in 2007
versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at
least 1 appointment (84% vs. 66%, p = 0.002). CONCLUSIONS: Multiple reasons for
treatment deferral were documented. Despite a significant improvement in
hepatology clinic attendance and an increase in the number of patients started on
treatment in 2007 compared to 2003, the overall percentage of those treated
remained low.
PMID- 28417753
TI - Mycoplasma genitalium presence, resistance and epidemiology in Greenland.
AB - Objectives . Greenland reports the highest rates of chlamydial infection and
gonorrhea in the Arctic. Our objective was to determine the presence, and
describe the basic epidemiology, of Mycoplasma genitalium for Greenland. Study
design . Cross-sectional study. Methods . 314 residents from Nuuk and Sisimiut,
between the ages of 15 and 65 years, participated in "Inuulluataarneq" (the
Greenland Sexual Health Project) between July 2008 and November 2009.
Participants provided self-collected samples for sexually transmitted infection
(STI) testing and completed a sexual health survey. Descriptive statistics and
logistic regression were used to summarize the basic characteristics of STI cases
overall and M. genitalium and Chlamydia trachomatis specifically. Clinically
relevant characteristics in each full model were gender (male or female), age (in
years), age at sexual debut (in years), number of sexual partners in the past 3
months (continuous) and history of forced sex and community. Results . The
overall prevalence of STIs was 19.0%, specifically: 9.8% for M. genitalium and
9.4% for C. trachomatis; 100% of M. genitalium-positive cases carried macrolide
resistance determinants. Being female [OR = 3.2; 95% confidence interval (CI):
1.1-9.8] and younger age (OR = 0.9; 95% CI: 0.9-1.0) were associated with M.
genitalium positivity. Age was also associated with C. trachomatis (OR = 0.9; 95%
CI: 0.8-0.9) and STI positivity overall (OR = 0.9; 95% CI: 0.9-0.9). Conclusions
. We observed a high prevalence of M. genitalium and macrolide resistance in this
study. A better understanding of M. genitalium sequelae is needed to inform
policy around testing, treatment, control and antibiotic use.
PMID- 28417754
TI - Alaska Native people's perceptions, understandings, and expectations for research
involving biological specimens.
AB - OBJECTIVES: Members of racially and ethnically diverse groups have been
persistently underrepresented in biomedical research in general, possibly due to
mistrust with the medical and research community. This article describes the
perceptions, understandings, and expectations of Alaska Native people about
research involving the collection and storage of biological specimens. STUDY
DESIGN: Stratified focus groups. METHODS: Twenty-nine focus groups with Alaska
Native people (n = 178) were held in 14 locations using a semi-structured
moderator guide. ATLAS.ti was used for thematic analysis through iterative
readings and coding. Alaska Native peoples' perceptions, understandings, and
expectations of researcher beneficence, informed consent processes, and provision
of research findings were elicited. RESULTS AND CONCLUSIONS: Alaska Native people
desired extensive disclosure of information beyond that typically provided in
consent and results dissemination processes. Information germane to the
motivation and intent of researchers and specifics of specimen storage and
destruction were specifically requested. A clear and extensive process of
informed consent and continued improvements in sharing results may enhance the
transparency of research intent, conduct, and use of obtained results among
Alaska Native people. Meeting expectations may improve relationships between
researchers and the Alaska Native population which could result in increased
research participation. Our findings offer a guide for researchers and
communities when planning and implementing research with biological specimens.
PMID- 28417755
TI - Oral health in a First Nations and a non-Aboriginal population in Manitoba.
AB - OBJECTIVES: To analyze the prevalence of poor oral health and selected
determinants in First Nations (FN) and Caucasian samples in Manitoba, Canada.
STUDY DESIGN: Cross-sectional survey, nested in a cohort study. METHODS: FN and
Caucasian participants completed a questionnaire on socio-demographic variables,
oral health symptoms, and oral health-related behaviours as part of a broader
cohort study comparing these ethnic groups for different chronic immune mediated
diseases. RESULTS: Caucasians reported higher levels of employment, education,
and urban dwelling than FNs (p<0.001). FNs reported smoking more, and having
poorer oral health-related behaviours than Caucasians (p<0.001). After adjustment
for age and sex, FN reported having more oral health symptoms than Caucasians
(odds ratio (OR): 2.71; 95% confidence interval (CI): 1.73, 4.52), but the
association was reduced and not statistically significant after adjustment for
other socio-demographic variables (OR=1.34; 95% CI: 0.58, 3.10). Oral health
symptoms were associated with current smoking among FN (adjusted OR=2.67, 95% CI:
1.05, 6.78). Oral hygiene behaviours were significantly related to smoking
status, rural living and education for both groups. CONCLUSIONS: Oral health
related behaviours and smoking were found to be significant factors explaining
poor oral health, which were lower for the FNs cohort than the Caucasian sample.
However oral health and related behaviours were less related to their ethnicity
than to socio-demographic factors, suggesting that policies to change behaviour
will not result in lasting reductions in oral health differences between these
groups in Manitoba.
PMID- 28417756
TI - Gender differences in comorbidity of conduct disorder among adolescents in
Northern Finland.
AB - OBJECTIVES: Conduct disorder (CD) refers to a pattern of severe antisocial and
aggressive behaviour manifested in childhood or adolescence, with heavy costs to
society. Though CD is a common psychiatric diagnosis among adolescents of both
genders, gender differences in comorbidity of CD have been little studied. In
this study we examined gender differences among adolescents with CD in causes for
hospitalization, comorbid psychiatric diagnoses and somatic conditions. STUDY
DESIGN: The original study sample consisted of 508 inpatient adolescents in
Northern Finland (age 12-17); 155 of them (65 girls, 92 boys) fulfilled the DSM
IV criteria for CD. METHODS: Diagnosis of CD and psychiatric comorbidities were
obtained from the K-SADS-PL and somatic conditions from the EuropAsi. RESULTS: As
compared to boys with CD, suicidality (including suicidal ideation and behaviour)
was significantly more commonly the cause of hospitalization among girls with CD
(43% vs. 24%, p=0.013). Among somatic conditions, there was a significant
predominance in self-reported allergies among girls (60% vs. 25%, p<0.001). Girls
had more often diagnosed comorbid post-traumatic stress disorder (13% vs. 3%,
p=0.025) and marginally significantly more major depressive disorder (36% vs.
23%, p=0.086). CONCLUSIONS: Girls with CD seem to have an increased tendency to
develop both comorbid psychiatric and somatic conditions as well as suicidality.
New clinical aspects in treatment of CD and comorbid disorders among girls are
discussed.
PMID- 28417757
TI - Assessment of consumption of marine food in Greenland by a food frequency
questionnaire and biomarkers.
AB - OBJECTIVES: We studied the association and agreement between questionnaire data
and biomarkers of marine food among Greenland Inuit. DESIGN: Cross sectional
study. METHODS: The study population comprised 2,224 Inuit, age 18+ (43% men);
data collected 2005-2008 in Greenland. Using a food frequency questionnaire
(FFQ), we calculated consumption of seal, whale, and fish (g/day) and as
meals/month, intake of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
total N3, and mercury. We measured erythrocyte membrane fatty acids (FA) and
whole blood mercury (Hg). Associations were assessed by Pearson correlation and
agreement between the 2 methods was assessed by Bland-Altman plots depicting mean
difference between the methods. Using multiple linear regressions, the
associations were studied between whole blood mercury, erythrocyte FA and
frequency or gram per day of seal, whale, and fish. RESULTS: Partial correlations
ranged from r=0.16, p<0.0001 (DHA) to r=0.56, p<0.0001 (mercury). The best fitted
lines were found for mercury and DHA. Mean difference was negative for mercury
but positive for all the FA biomarkers. In a multiple logistic regression
analysis, the best association was found between whole blood mercury and seal
consumption, both as frequency in meals and actual intake gram per day: beta=1.07
ug (95% CI: 1.06; 1.08) and beta=1.04 ug (95% CI: 1.03; 1.04), respectively.
CONCLUSION: Mercury showed the best correlation and agreement between calculated
and measured values. Calculated actual intake in gram per day and frequency of
meals showed similar associations with whole blood mercury and erythrocyte
membrane FAs.
PMID- 28417758
TI - The impact of Action Schools! BC on the health of Aboriginal children and youth
living in rural and remote communities in British Columbia.
AB - OBJECTIVES: The aim of the study was to determine the short-term impact of a 7
month whole-school physical activity and healthy eating intervention (Action
Schools! BC) over the 2007-2008 school year for children and youth in 3 remote
First Nations villages in northwestern British Columbia. STUDY DESIGN: A pre
experimental pre/post design was conducted with 148 children and youth (77 males,
71 females; age 12.5+/-2.2 yrs). METHODS: We evaluated changes in obesity (body
mass index [wt/ht2] and waist circumference z-scores: zBMI and zWC), aerobic
fitness (20-m shuttle run), physical activity (PA; physical activity
questionnaire and accelerometry), healthy eating (dietary recall) and
cardiovascular risk (CV risk). RESULTS: zBMI remained unchanged while zWC
increased from 0.46+/-1.07 to 0.57+/-1.04 (p<0.05). No change was detected in PA
or CV risk but aerobic fitness increased by 22% (25.4+/-15.8 to 30.9+/-20.0 laps;
p<0.01). There was an increase in the variety of vegetables consumed (1.10+/-1.18
to 1.45+/-1.24; p<0.05) but otherwise no dietary changes were detected.
CONCLUSIONS: While no changes were seen in PA or overall CV risk, zWC increased,
zBMI remained stable and aerobic fitness improved during a 7-month intervention.
1Published 'ahead-of-print' 2 December 2011 (at www.ijch.fi ) in accordance with
previous publisher's routines.
PMID- 28417759
TI - Level and temporal trend of perfluoroalkyl acids in Greenlandic Inuit.
AB - OBJECTIVES: Perfluoroalkyl acids (PFAAs) have been detected in human blood,
breast milk and umbilical cord blood across the globe. PFAAs do accumulate in the
marine food chain in Arctic regions. In Greenland, increasing PFAA concentrations
were observed during 1982-2006 in ringed seals and polar bears. However, until
now, no data have been reported for PFAAs in Greenlandic Inuit. This study
assesses the level and temporal trend of serum PFAAs in Greenlandic Inuit. STUDY
DESIGN: Cross-section and temporal time trend survey. METHODS: Serum PFAA levels
were determined in 284 Inuit from different Greenlandic districts using liquid
chromatography-tandem mass spectrometry with electrospray ionization. The
temporal time trend of serum PFAAs in Nuuk Inuit during 1998-2005 and the
correlation between serum PFAAs and legacy persistent organic pollutants (POPs)
were explored. RESULTS: Serum PFAA levels were higher in Nuuk Inuit than in non
Nuuk Inuit. Within the same district, higher PFAA levels were observed for males.
An age-dependent, increasing trend of serum PFAA levels in the period from 1998
2005 was observed for Nuuk Inuit. For the pooled gender data, no significant
association between PFAAs and legacy POPs was observed for Nuuk Inuit while for
non-Nuuk Inuit this correlation was significant. No correlation between PFAAs and
legacy POPs was found for male Inuit, whereas significant correlation was
observed both for pooled female Inuit and for non-Nuuk Inuit females.
CONCLUSIONS: We suggest that sources other than seafood intake might contribute
to the observed higher PFAA levels in Nuuk Inuit compared to the pooled non-Nuuk
Inuit. 1Published 'ahead-of-print' 13 December 2011 (at www.ijch.fi ) in
accordance with previous publisher's routines.
PMID- 28417760
TI - Sami-speaking municipalities and a control group's access to somatic specialist
health care (SHC): a retrospective study on general practitioners' referrals.
AB - OBJECTIVES: The Sami people constitute the indigenous people in northern Norway.
The objective of this study was to clarify whether they have a similar supply of
somatic specialist health care (SHC) as others. METHODS: The referrals from
general practitioners (GPs) in the primary health care (PHC) in the
administration area of the Sami language law (8 municipalities) were matched with
a control group of 11 municipalities. Population data was accessed from
Statistics Norway and the time period 2007-2010 was analysed. The main outcome
was the number of referrals per 1,000 inhabitants according to age group, gender
and place of living. RESULTS: 504,292 referrals in northern Norway were
indentified and the Sami and control group constituted 23,093 and 22,541
referrals, respectively. The major findings were a similar referral ratio (RR)
(1.14 and 1.17) (p = 0.624) and women more commonly referred (female/male ratio
1.45 and 1.41) in both groups. GPs in both groups were loyal to their local
hospital trust. CONCLUSION: Inhabitants in Sami-speaking municipalities in
northern Norway have a similar supply of SHC services as controls. Inter
municipal variation was significant in both groups.
PMID- 28417761
TI - Obesity studies in the circumpolar Inuit: a scoping review.
AB - BACKGROUND: Among circumpolar populations, recent research has documented a
significant increase in risk factors which are commonly associated with chronic
disease, notably obesity. OBJECTIVE: The present study undertakes a scoping
review of research on obesity in the circumpolar Inuit to determine the extent
obesity research has been undertaken, how well all subpopulations and geographic
areas are represented, the methodologies used and whether they are sufficient in
describing risk factors, and the prevalence and health outcomes associated with
obesity. DESIGN: Online databases were used to identify papers published 1992
2011, from which we selected 38 publications from Canada, the United States, and
Greenland that used obesity as a primary or secondary outcome variable in 30 or
more non-pregnant Inuit ("Eskimo") participants aged 2 years or older. RESULTS:
The majority of publications (92%) reported cross-sectional studies while 8%
examined retrospective cohorts. All but one of the studies collected measured
data. Overall 84% of the publications examined obesity in adults. Those examining
obesity in children focused on early childhood or adolescence. While most (66%)
reported 1 or more anthropometric indices, none incorporated direct measures of
adiposity. Evaluated using a customized quality assessment instrument, 26% of
studies achieved an "A" quality ranking, while 18 and 39% achieved quality
rankings of "B" and "C", respectively. CONCLUSIONS: While the quality of studies
is generally high, research on obesity among Inuit would benefit from careful
selection of methods and reference standards, direct measures of adiposity in
adults and children, studies of preadolescent children, and prospective cohort
studies linking early childhood exposures with obesity outcomes throughout
childhood and adolescence.
PMID- 28417762
TI - Room for improvement in diabetes care among First Nations in northern Quebec
(Eeyou Istchee): reasonable management of glucose but poor management of
complications.
AB - OBJECTIVES: To evaluate the clinical management of type 2 diabetes in the Eeyou
Istchee communities of northern Quebec. STUDY DESIGN: Retrospective quality
assurance audit. METHODS: Patients with diabetes were identified using the Cree
Diabetes Information System. Charts of eligible patients were audited for
healthcare visits, glycemic control, blood pressure, lipid profile,
pharmacological treatment and complications for the 2006 calendar year. Analyses
were performed to assess the association of disease duration, age, target
glycemic and blood pressure control with diabetes complications. RESULTS: Half of
the patients (49.7%) achieved target HbA1c, 53.6% had a blood pressure of
<=130/80 and 58.7% had an LDL of <=2.5 mmol/L. The proportion of patients meeting
all 3 targets was low at 17.1%. The mean number of diabetes-related clinic visits
was high, with an average of 3.9 visits to a physician and an average of 8.7
visits to a registered nurse. Of patients with a documented diabetic
complication, 39.4% of patients were not being managed with an ACE/ARB and 48.2%
of patients were not prescribed a statin. CONCLUSIONS: These findings suggest a
possible treatment gap for risk factors and complications management. To
circumvent further increases in diabetes-related complications, emphasis should
be placed on improved healthcare worker training, greater use of clinical
management and patient education tools and improved communication during the
diabetes-related clinical visits. Development of a culturally appropriate
multidisciplinary approach towards improved understanding of diabetes and
multifactorial risk management for diabetic patients is essential for the
prevention of diabetic complications.
PMID- 28417763
TI - Design and methods in a survey of living conditions in the Arctic - the SLiCA
study.
AB - OBJECTIVES: The main objective of this study is to describe the methods and
design of the survey of living conditions in the Arctic (SLiCA), relevant
participation rates and the distribution of participants, as applicable to the
survey data in Alaska, Greenland and Norway. This article briefly addresses
possible selection bias in the data and also the ways to tackle it in future
studies. STUDY DESIGN: Population-based cross-sectional survey. METHODS:
Indigenous individuals aged 16 years and older, living in Greenland, Alaska and
in traditional settlement areas in Norway, were invited to participate. Random
sampling methods were applied in Alaska and Greenland, while non-probability
sampling methods were applied in Norway. Data were collected in 3 periods: in
Alaska, from January 2002 to February 2003; in Greenland, from December 2003 to
August 2006; and in Norway, in 2003 and from June 2006 to June 2008. The
principal method in SLiCA was standardised face-to-face interviews using a
questionnaire. RESULTS: A total of 663, 1,197 and 445 individuals were
interviewed in Alaska, Greenland and Norway, respectively. Very high overall
participation rates of 83% were obtained in Greenland and Alaska, while a more
conventional rate of 57% was achieved in Norway. A predominance of female
respondents was obtained in Alaska. Overall, the Sami cohort is older than the
cohorts from Greenland and Alaska. CONCLUSIONS: Preliminary assessments suggest
that selection bias in the Sami sample is plausible but not a major threat. Few
or no threats to validity are detected in the data from Alaska and Greenland.
Despite different sampling and recruitment methods, and sociocultural
differences, a unique database has been generated, which shall be used to explore
relationships between health and other living conditions variables.
PMID- 28417764
TI - Self-rated health and ethnicity: focus on indigenous populations.
AB - OBJECTIVES: Self-rated health (SRH) is a commonly used measure in surveys to
assess general health status or health-related quality of life. Differences have
been detected in how different ethnic groups and nationalities interpret the SRH
measure and assess their health. This review summarizes the research conducted on
SRH within and between ethnic groups, with a focus on indigenous groups. STUDY
DESIGN AND METHODS: A search of published academic literature on SRH and
ethnicity, including a comprehensive review of all relevant indigenous research,
was conducted using PubMed and summarized. RESULTS: A wide variety of research on
SRH within ethnic groups has been undertaken. SRH typically serves as an outcome
measure. Minority respondents generally rated their health worse than the
dominant population. Numerous culturally-specific determinants of SRH have been
identified. Cross-national and cross-ethnicity comparisons of the associations of
SRH have been conducted to assess the validity of SRH. While SRH is a valid
measure within a variety of ethnicities, differences in how SRH is assessed by
ethnicities have been detected. Research in indigenous groups remains generally
under-represented in the SRH literature. CONCLUSIONS: These results suggest that
different ethnic groups and nationalities vary in SRH evaluations, interpretation
of the SRH measure, and referents employed in rating health. To effectively
assess and redress health disparities and establish culturally-relevant and
effective health interventions, a greater understanding of SRH is required,
particularly among indigenous groups, in which little research has been
conducted.
PMID- 28417765
TI - High prevalence of lactase non-persistence among indigenous nomadic Nenets, north
west Russia.
AB - Objectives The frequency of adult-type hypolactasia (lactase non-persistence)
varies widely among different ethnic groups. The cultural historical hypothesis
assumes a link between the occurrence of hypolactasia and the distribution of
dairy farming. The nomadic Nenets have been reindeer herders for generations and
have therefore not consumed any dairy products. The hypotheses here was that the
prevalence of lactase non-persistence (-13910 C/C genotype) among Nenets people
having four Nenets grandparents is high, while the prevalence among Nenets
originating from ethnically mixed families is lower. Study design The material
was collected in four typical Nenets settlements in the Nenets Autonomous Okrug
in Russia. One-third of the adult Nenets population were invited to answer a
questionnaire and to donate buccal samples for genotyping by a doctor from the
team of medical professionals who make rounds in this area. The total number of
available participants was 177. Methods Genotyping was performed with the
AbiPrism system. We used the method of concordance of grandparents' national
origin to ascribe ethnicity. Results The prevalence of adult-type hypolactasia (
13910 C/C) among Nenets who had four Nenets grandparents was found to be 90%. The
figures among others reporting three, two and one grandparent of Nenets origin
were 72, 60 and 28%, respectively. Conclusion The findings are in accord with the
cultural historical hypothesis.
PMID- 28417766
TI - The best of two worlds: how the Greenland Board of Nutrition has handled
conflicting evidence about diet and health.
AB - The traditional diet in Greenland consists to a large extent of meat and organs
of seal and other marine mammals, which is polluted by POPs and mercury. These
substances are present in the blood of Greenlanders in concentrations well above
international guidelines, and as these contaminants are suspected of having
negative impacts on health, some action should be taken. On the other hand,
traditional food is also an important source of health promoting micronutrients
that are not provided by imported food in sufficient quantities, for example
vitamin D, long chain n-3 fatty acids, and selenium, not to mention the
traditional diet's function as a social glue that is perceived as important for
Inuit identity in Greenland. The proportion of the total diet that comes from
marine mammals is on a constant decrease, and especially children and young
adults consume rather little seal and whale. The traditional food items are
consequently being replaced by imported food, and among the imported food items
several rather unhealthy items are popular, that is carbonated soft drinks with
sugar, sweets, chips and farmed (red) meat with a high content of saturated fat.
Together with a decrease in physical activity, this dietary transition has
resulted in a severe epidemic of overweight and diabetes. In giving advice to the
public, the Greenland Board of Nutrition was therefore faced with the challenge
to retain the benefits of the traditional diet while minimizing the contaminant
exposure, and at the same time to counteract the effects of poor quality imported
food. The Board tried to balance the known and suspected positive and negative
aspects of the total diet in relation not only to physical health but to general
wellbeing, and decided on 10 simple recommendations. As the consumption of
traditional food becomes less prominent and as the consumption of food rich in
empty calories increases, the guidelines are continuously revised and updated.
PMID- 28417767
TI - IJCH Enters a New Era.
PMID- 28417768
TI - Vitamin D deficiency among northern Native Peoples: a real or apparent problem?
AB - Vitamin D deficiency seems to be common among northern Native peoples, notably
Inuit and Amerindians. It has usually been attributed to: (1) higher latitudes
that prevent vitamin D synthesis most of the year; (2) darker skin that blocks
solar UVB; and (3) fewer dietary sources of vitamin D. Although vitamin D levels
are clearly lower among northern Natives, it is less clear that these lower
levels indicate a deficiency. The above factors predate European contact, yet pre
Columbian skeletons show few signs of rickets-the most visible sign of vitamin D
deficiency. Furthermore, because northern Natives have long inhabited high
latitudes, natural selection should have progressively reduced their vitamin D
requirements. There is in fact evidence that the Inuit have compensated for
decreased production of vitamin D through increased conversion to its most active
form and through receptors that bind more effectively. Thus, when diagnosing
vitamin D deficiency in these populations, we should not use norms that were
originally developed for European-descended populations who produce this vitamin
more easily and have adapted accordingly. 1Published 'ahead-of-print' 10 November
2011 (at www.ijch.fi ) in accordance with previous publisher's routines.
PMID- 28417769
TI - Innovative primary care delivery in rural Alaska: a review of patient encounters
seen by community health aides.
AB - BACKGROUND: For more than 50 years, Community Health Aides and Community Health
Practitioners (CHA/Ps) have resided in and provided care for the residents of
their villages. OBJECTIVES: This study is a systematic description of the
clinical practice of primary care health workers in rural Alaska communities.
This is the first evaluation of the scope of health problems seen by these lay
health workers in their remote communities. STUDY DESIGN: Retrospective
observational review of administrative records for outpatient visits seen by
CHA/Ps in 150 rural Alaska villages (approximate population 47,370). METHODS:
Analysis of electronic records for outpatient visits to CHA/Ps in village clinics
from October 2004 through September 2006. Data included all outpatient visits
from the Indian Health Service National Patient Information Reporting System.
Descriptive analysis included comparisons by region, age, sex, clinical
assessment and treatment. RESULTS: In total 272,242 visits were reviewed. CHA/Ps
provided care for acute, chronic, preventive, and emergency problems at 176,957
(65%) visits. The remaining 95,285 (35%) of records did not include a diagnostic
code, most of which were for administrative or medication-related encounters. The
most common diagnostic codes were: pharyngitis (11%), respiratory infections
(10%), otitis media (8%), hypertension (6%), skin infections (4%), and chronic
lung disease (4%). Respiratory distress and chest pain accounted for 75%
(n=10,552) of all emergency visits. CONCLUSIONS: CHA/Ps provide a broad range of
primary care in remote Alaskan communities whose residents would otherwise be
without consistent medical care. Alaska's CHA/P program could serve as a health
care delivery model for other remote communities with health care access
challenges. To access the supplementary material to this article: 'NPIRS
Categorical Hierarchy' please see the Supplementary files under Article Tools
online.
PMID- 28417770
TI - Level of selected toxic elements in meat, liver, tallow and bone marrow of young
semi-domesticated reindeer (Rangifer tarandus tarandus L.) from Northern Norway.
AB - Objectives . To gain knowledge on toxic elements in semi-domesticated reindeer
and their distribution in meat, liver, tallow and bone marrow. The correlations
between concentrations in meat and liver, as well as the use of the latter as an
indicator for toxic elements in meat, were also investigated. Study design .
Cross-sectional study on population of semi-domesticated reindeer from 2 northern
Norwegian counties (Finnmark and Nordland). Methods . Semi-domesticated reindeer
carcasses (n = 31) were randomly selected, from which meat, liver, tallow and
bone marrow samples were collected. Selected toxic elements (cadmium, lead,
arsenic, nickel and vanadium) were studied. Results . Liver was the organ with
the highest level of all elements except for nickel, which was highest in bone
marrow. Meat had the lowest levels, whereas levels in tallow and bone marrow were
between those of meat and liver. Concentrations of cadmium, lead and arsenic were
significantly different (p < 0.05) between meat and liver, while only arsenic and
cadmium were significantly correlated in meat (rs=0.71, p < 0.01) and liver
(rs=0.72, p < 0.01). The cadmium level exceeded the European Commission's (EC)
maximum level set for bovine meat and live in 52% of the liver samples (n = 29).
Nevertheless, the estimated monthly cadmium intake from liver of 2.29 ug/kg body
weight was well below the provisional tolerable monthly intake of 25 ug/kg body
weight set by the FAO/WHO Joint Expert Committee on Food Additives. Conclusions .
Based on the measured levels and their relation to the maximum level and to the
provisional tolerable weekly/monthly intake limits, it could be inferred that
consumption of reindeer meat is not associated with any health risk related to
the studied toxic elements for consumers.
PMID- 28417771
TI - The international biological program/human adaptability studies among the Skolt
Sami in Finland (1966-1970).
AB - BACKGROUND: The population is increasingly lighter pigmented moving in a
northward direction in Europe until reaching the Arctic Circle, where the Samis
(Lapps) are clearly more pigmented. METHODS: In 1966-1970, we investigated a
total of 689 subjects in the villages of Sevettijarvi and Nellim, including
persons with mixed Sami and Finnish heritage; of these, 487 (242 males, 245
females) had both parents classified as Skolt Sami. For estimation of the colour
of the iris and hair, international scales were used. For translucency of the
iris, pigmentation of the fundus was estimated in 3 different shades. The length
and type of eyelashes were classified into 3 categories. To our knowledge, a
simultaneous study of the pigmentation of eyebrows, eyelashes and eye fundus at
different ages has not previously been published. RESULTS: The age differences of
iris colour were highly significant. Iris colour in children varied markedly, and
they generally had lighter colours than later in life. Age and sex effects on the
translucency of irises were found. Male irises were more translucent. Fundus
pigmentation was scanty in the youngest age groups, with full pigmentation being
reached at 20 years. Among young individuals hair colour darkens with increasing
age. Eyebrow colour was slightly lighter for both sexes in the youngest age
groups that in older cohorts. Women had longer eyelashes than males. CONCLUSIONS:
The main factor of the lighter skin is a higher ability to synthesize vitamin D,
providing superior protection against rickets. The Skolt Samis are more pigmented
than other Nordic people. In earlier times they had problems with rickets but our
studies did not show any essential symptoms of rickets today. Visual acuity among
Skolt Samis was good. They had lower prevalence of myopia compared to Finns. The
stronger pigmentation of Skolt Samis is probably due to their origin from darker
Eastern populations. Since our investigations were made, the Skolt Samis have
been to a great part mixed with neighbouring populations and scattered throughout
Finland. Even their old language is nowadays used mainly for traditional
purposes. Therefore similar studies could not be performed anymore.
PMID- 28417772
TI - A decade of research in Inuit children, youth, and maternal health in Canada:
areas of concentrations and scarcities.
AB - Inuit Canadians are on average about 20 years younger and have a 10-year lower
life expectancy than other Canadians. While there have been improvements in Inuit
health status over time, significant health disparities still remain. This paper
will review the peer-reviewed literature related to Inuit child, youth, and
maternal health between 2000 and 2010, investigate which thematic areas were
examined, and determine what proportion of the research is related to each group.
Establishing areas of research concentrations and scarcities may help direct
future research where it is needed. We followed a systematic literature review
and employed peer-reviewed research literature on child, youth, and maternal
health which were selected from 3 sources, MEDLINE, CINAHL, and the Circumpolar
Health Bibliographic Database. The resulting references were read, and summarized
according to population group and thematic area. The thematic areas that emerged
by frequency were: infectious disease; environment/environmental exposures;
nutrition; birth outcomes; tobacco; chronic disease; health care; policy, human
resources; interventions/programming; social determinants of health; mental
health and wellbeing; genetics; injury; and dental health. The 72 papers that met
the inclusion criteria were not mutually exclusive with respect to group studied.
Fifty-nine papers (82%) concerned child health, 24 papers (33%) youth health, and
58 papers (81%) maternal health. The review documented high incidences of illness
and significant public health problems; however, in the context of these issues,
opportunities to develop research that could directly enhance health outcomes are
explored.
PMID- 28417773
TI - Cancer patterns in Inuit Nunangat: 1998-2007.
AB - Objectives . To compare cancer incidence patterns between residents of Inuit
Nunangat and the rest of Canada. Study design . Cancer cases were geographically
linked to either Inuit Nunangat or the rest of Canada using postal codes or other
geographic information. Population estimates were derived from the 2001 and 2006
censuses. Methods . Cancer cases were combined from 1998 to 2007 for Inuit
Nunangat and the rest of Canada. Age-standardised incidence rates were calculated
for all site cancers and sub-sites by sex. Standardised rate ratios between these
2 areas were calculated for all site cancers and sub-sites. Results . The age
standardised incidence rate for all cancer sites (1998-2007) was 14% lower for
the Inuit Nunangat male population and 29% higher for the female population by
comparison to the rest of Canada. Cancers of the nasopharynx, lung and bronchus,
colorectal, stomach (males), and kidney and renal pelvis (females), were elevated
in the Inuit Nunangat population compared to the rest of Canada, whereas prostate
and female breast cancers were lower in the Inuit Nunangat population.
Conclusions . Cancers with potentially modifiable risk factors, such as buccal
cavity and pharynx, nasopharynx, lung and bronchus, and colorectal cancer were
elevated in the Inuit Nunangat population compared to the rest of Canada. Besides
greater smoking prevalence within Inuit Nunangat by comparison to the rest of
Canada, distinct socioeconomic characteristics between respective area
populations including housing, and income may have contributed to incidence
differentials. This study demonstrated that a geographic approach can be used in
cancer surveillance when populations of interest are spatially distinguishable,
and reside across distinct jurisdictions whose combined cancer registries will
not completely provide information to identify the population of interest.
PMID- 28417774
TI - The health of young Swedish Sami with special reference to mental health.
AB - OBJECTIVES: To investigate the health of young Sami in Sweden and the
relationship between health and experience of negative societal treatment due to
ethnicity, as well as socio-demographic background factors. STUDY DESIGN: Cross
sectional population-based questionnaire study. METHODS: A total of 876 persons
aged 18-28 and involved in Sami associated activities were addressed, and 516
(59%) responded to a questionnaire investigating physical health, mental health,
and stress. Data were analyzed with regard to gender, family situation,
occupation, education, enculturation factors and experience of being badly
treated because of ethnicity. RESULTS: A majority of the young Sami reported
feeling healthy, but close to half of the group reported often having worries,
often forgetting things and often experiencing lack of time for doing needed
things. Women and those living alone reported a more negative health.
Furthermore, half of the group had perceived bad treatment because of Sami
ethnicity, and this was negatively associated with some aspects of mental health.
CONCLUSION: The young Sami had a rather good and possibly slightly better health
than other young Swedes, except regarding worries and stress. A high degree of
bad treatment due to Sami ethnicity and its negative association with health, may
partly explain the high degree of some health problems.
PMID- 28417775
TI - Breast cancer in the Arctic - changes over the past decades.
AB - The purpose of this study is to review the current literatures on breast cancer
(BC) in the Arctic, especially the trends in incidence during the last decades
and the possible explanations. The design of this study is a literature review.
The scientific literature concerning BC were reviewed, especially focusing on the
Arctic and the special conditions that exist in this region. Breast cancer
incidence is increasing all over the world, including in the Arctic. The enormous
transition in health conditions and lifestyle in the Arctic might be contributing
to the known risk factors. In Greenland, the age at menarche has diminished by 3
years during the course of 100 years, and the number of children per women as
well as the duration of breastfeeding is decreasing. Obesity and intake of
saturated fat is increasing and the intake of traditional food rich in
unsaturated fat and vitamin D decreasing. Smoking and alcohol consumption in the
Arctic has been relatively high but is now decreasing. More focus on genetic
susceptibility in relation to BC has identified the specific BRCA1 founder
mutation in the Greenlandic population, which might appear to be an important
risk factor. However, the known established risk factors alone cannot account for
the increasing trend observed. Studies suggest that environmental contaminants
such as persistent organic pollutants (POPs) including perfluorinated compounds
increase the risk of BC possibly in conjunction with certain genetic
polymorphisms involved in carcinogen activation. The lipophilic POPs such as
polychlorinated biphenyls and organochlorine pesticides are found at very high
levels in the Arctic population. Several factors can explain the increasing
incidence of BC in the Arctic. The transition in lifestyle and health conditions
unfortunately increases the known risk factors of BC. Moreover, the population of
the Arctic might show up to be especially vulnerable because of the contemporary
high burden of POPs and genetic susceptibility.
PMID- 28417776
TI - Suicidal ideation among Metis adult men and women - associated risk and
protective factors: findings from a nationally representative survey.
AB - OBJECTIVE: To determine the prevalence of suicidal ideation among Metis men and
women (20-59 years) and identify its associated risk and protective factors using
data from the nationally representative Aboriginal Peoples Survey (2006). STUDY
DESIGN: Secondary analysis of previously collected data from a nationally
representative cross-sectional survey. RESULTS: Across Canada, lifetime suicidal
ideation was reported by an estimated 13.3% (or an estimated 34,517 individuals)
of the total population of 20-to-59-year-old Metis. Of those who ideated, 46.2%
reported a lifetime suicide attempt and 6.0% indicated that they had attempted
suicide in the previous 12 months. Prevalence of suicidal ideation was higher
among Metis men than in men who did not report Aboriginal identity in examined
jurisdictions. Metis women were more likely to report suicidal ideation compared
with Metis men (14.9% vs. 11.5%, respectively). Metis women and men had some
common associated risk and protective factors such as major depressive episode,
history of self-injury, perceived Aboriginal-specific community issues, divorced
status, high mobility, self-rated thriving health, high self-esteem and positive
coping ability. However, in Metis women alone, heavy frequent drinking, history
of foster care experience and lower levels of social support were significant
associated risk factors of suicidal ideation. Furthermore, a significant
interaction was observed between social support and major depressive episode.
Among Metis men, history of ever smoking was the sole unique associated risk
factor. CONCLUSION: The higher prevalence of suicidal ideation among Metis women
compared with Metis men and the observed gender differences in associations with
some associated risk and protective factors suggest the need for gender
responsive programming to address suicidal ideation.
PMID- 28417778
TI - The State of the Journal.
PMID- 28417777
TI - Healthcare use for acute gastrointestinal illness in two Inuit communities:
Rigolet and Iqaluit, Canada.
AB - Background The incidence of self-reported acute gastrointestinal illness (AGI) in
Rigolet, Nunatsiavut, and Iqaluit, Nunavut, is higher than reported elsewhere in
Canada; as such, understanding AGI-related healthcare use is important for
healthcare provision, public health practice and surveillance of AGI. Objectives
This study described symptoms, severity and duration of self-reported AGI in the
general population and examined the incidence and factors associated with
healthcare utilization for AGI in these 2 Inuit communities. Design Cross
sectional survey data were analysed using multivariable exact logistic regression
to examine factors associated with individuals' self-reported healthcare and over
the-counter (OTC) medication utilization related to AGI symptoms. Results In
Rigolet, few AGI cases used healthcare services [4.8% (95% CI=1.5-14.4%)]; in
Iqaluit, some cases used healthcare services [16.9% (95% CI=11.2-24.7%)]. Missing
traditional activities due to AGI (OR=3.8; 95% CI=1.18-12.4) and taking OTC
medication for AGI symptoms (OR=3.8; 95% CI=1.2-15.1) were associated with
increased odds of using healthcare services in Iqaluit. In both communities, AGI
severity and secondary symptoms (extreme tiredness, headache, muscle pains,
chills) were significantly associated with increased odds of taking OTC
medication. Conclusions While rates of self-reported AGI were higher in Inuit
communities compared to non-Inuit communities in Canada, there were lower rates
of AGI-related healthcare use in Inuit communities compared to other regions in
Canada. As such, the rates of healthcare use for a given disease can differ
between Inuit and non-Inuit communities, and caution should be exercised in
making comparisons between Inuit and non-Inuit health outcomes based solely on
clinic records and healthcare use.
PMID- 28417779
TI - How are your berries? Perspectives of Alaska's environmental managers on trends
in wild berry abundance.
AB - Background Wild berries are a valued traditional food in Alaska. Phytochemicals
in wild berries may contribute to the prevention of vascular disease, cancer and
cognitive decline, making berry consumption important to community health in
rural areas. Little was known regarding which species of berries were important
to Alaskan communities, the number of species typically picked in communities and
whether recent environmental change has affected berry abundance or quality.
Objective To identify species of wild berries that were consumed by people in
different ecological regions of Alaska and to determine if perceived berry
abundance was changing for some species or in some regions. Design We asked
tribal environmental managers throughout Alaska for their views on which among 12
types of wild berries were important to their communities and whether berry
harvests over the past decade were different than in previous years. We received
responses from 96 individuals in 73 communities. Results Berries that were
considered very important to communities differed among ecological regions of
Alaska. Low-bush blueberry (Vaccinium uliginosum and V. caespitosum), cloudberry
(Rubus chamaemorus) and salmonberry (Rubus spectabilis) were most frequently
identified as very important berries for communities in the boreal, polar and
maritime ecoregions, respectively. For 7 of the 12 berries on the survey, a
majority of respondents indicated that in the past decade abundance had either
declined or become more variable. Conclusions Our study is an example of how
environmental managers and participants in local observer networks can report on
the status of wild resources in rural Alaska. Their observations suggest that
there have been changes in the productivity of some wild berries in the past
decade, resulting in greater uncertainty among communities regarding the security
of berry harvests. Monitoring and experimental studies are needed to determine
how environmental change may affect berry abundance.
PMID- 28417780
TI - Prevalence of self-reported myocardial infarction in Sami and non-Sami
populations: the SAMINOR study.
AB - Objective Measure the prevalence of self-reported myocardial infarction (SMI) in
Sami and non-Sami populations in rural areas of Norway, and explore whether
possible ethnic differences could be explained by established cardiovascular risk
factors. Design Cross-sectional population-based study. Methods A health survey
was conducted in 2003-2004 in areas with Sami and non-Sami populations (SAMINOR).
The response rate was 60.9%. Information concerning lifestyle was collected by 2
self-administrated questionnaires, and clinical examinations provided
anthropometric measurements, and data on blood pressure and lipid levels. Results
The total number for the subsequent analysis was 15,206 men and women aged 36-79
years (born 1925-1968). Sex-specific analyses revealed no ethnic difference in
SMI. In terms of the most important risk factors such as smoking, blood pressure,
and lipid levels, no or only trivial ethnic differences were found in both women
and men. Conclusion In this study, we found no difference in SMI between Sami and
non-Sami in rural areas in Norway. The similar risk profile is the most plausible
explanation; similar living conditions and close interaction between the ethnic
groups may explain this.
PMID- 28417782
TI - The process of developing a community-based research agenda with lesbian, gay,
bisexual, transgender and queer youth in the Northwest Territories, Canada.
AB - Background Youth in Canada's Northwest Territories (NWT) experience sexual and
mental health disparities. Higher rates of sexual and mental health concerns
among lesbian, gay, bisexual, transgender and queer (LGBTQ) youth in comparison
with heterosexual and cisgender peers have been associated with stigma and
discrimination. Although LGBTQ youth in the NWT are situated at the nexus of
Northern and LGBTQ health disparities, there is little known about their health,
well-being and experiences of stigma. This short communication discusses the
process of developing a LGBTQ youth community-based research programme in the
NWT. Methods We developed an interdisciplinary research team of LGBTQ and allied
young adults, including indigenous and non-indigenous researchers, community
organisers and service providers in the NWT. We conducted meetings in Yellowknife
with LGBTQ youth (n=12) and key stakeholders (n=15), including faculty, students,
community groups and health and social service providers. Both meetings included
LGBTQ and allied participants who were LGBTQ, indigenous, youth and persons at
the intersection of these identities. Results LGBTQ youth participants discussed
community norms that devalued same sex identities and stigma surrounding LGBTQ
specific services and agencies. Stigma among LGBT youth was exacerbated for youth
in secondary schools, gender non-conforming and transgender youth and young gay
men. In the stakeholder meeting, service providers discussed the importance of
integrating LGBTQ issues in youth programmes, and LGBTQ community groups
expressed the need for flexibility in service delivery to LGBTQ youth.
Stakeholders identified the need to better understand the needs of indigenous
LGBTQ youth in the NWT. Conclusions Community-based LGBTQ groups, researchers and
health and social service providers are interested in addressing LGBTQ youth
issues in the NWT. The emergence of LGBTQ community building, support groups and
activism in Northern Canada suggests that this is an opportune time to explore
LGBTQ youth health.
PMID- 28417781
TI - Undesirable financial effects of head and neck cancer radiotherapy during the
initial treatment period.
AB - Background Healthcare cost and reforms are at the forefront of international
debates. One of the current discussion themes in oncology is whether and how
patients' life changes due to costs of cancer care. In Norway, the main part of
the treatment costs is supported by general taxpayer revenues. Objectives The
objective of this study was to clarify whether head and neck cancer patients
(n=67) in northern Norway experienced financial health-related quality of life
(HRQOL) deterioration due to costs associated with treatment. Design HRQOL was
examined by the European Organization for Research and Treatment of Cancer
(EORTC) QLQ-C30 in the beginning and in the end of radiation treatment in
patients treated at the University Hospital in Northern Norway. Changes in
financial HRQOL were calculated and compared by paired sample T-tests. Multiple
regression analyses were used to examine correlations among gender, marital
status, age and treatment with or without additional chemotherapy and changes in
the HRQOL domain of financial difficulties. Results The majority of score results
at both time points were in the lower range (mean 15-25), indicating limited
financial difficulties. We observed no statistically significant differences by
gender, marital status and age. Increasing financial difficulties during
treatment were reported by male patients and those younger than 65, that is,
patients who were younger than retirement age. The largest effect was seen in
singles. However, differences were not statistically significant. Conclusions
During the initial phase of the disease trajectory, no significant increase in
financial difficulties was found. This is in line with the aims of the Norwegian
public healthcare model. However, long-term longitudinal studies should be
performed, especially with regard to the trends we observed in single, male and
younger patients.
PMID- 28417783
TI - Digital storytelling: a tool for health promotion and cancer awareness in rural
Alaskan communities.
AB - Background The purpose of this study was to learn community members' perspectives
about digital storytelling after viewing a digital story created by a Community
Health Aide/Practitioner (CHA/P). Methods Using a qualitative research design, we
explored digital storytelling likeability as a health-messaging tool, health
information viewers reported learning and, if viewing, cancer-related digital
stories facilitated increased comfort in talking about cancer. In addition, we
enquired if the digital stories affected how viewers felt about cancer, as well
as if viewing the digital stories resulted in health behaviour change or intent
to change health behaviour. Findings A total of 15 adult community members
participated in a 30-45 minute interview, 1-5 months post-viewing of a CHA/P
digital story. The majority (13) of viewers interviewed were female, all were
Alaska Native and they ranged in age from 25 to 54 years with the average age
being 40 years. Due to the small size of communities, which ranged in population
from 160 to 2,639 people, all viewers knew the story creator or knew of the story
creator. Viewers reported digital stories as an acceptable, emotionally engaging
way to increase their cancer awareness and begin conversations. These
conversations often served as a springboard for reflection, insight, and cancer
prevention and risk-reduction activities.
PMID- 28417784
TI - Whiteboard animation for knowledge mobilization: a test case from the Slave River
and Delta, Canada.
AB - Objective To present the co-creation of a whiteboard animation video, an enhanced
e-storytelling technique for relaying traditional knowledge interview results as
narratives. Design We present a design for translating interview results into a
script and accompanying series of figures, followed by technical steps to create
a whiteboard animation product. Method Our project used content analysis and
researcher triangulation, followed by a collaborative process to develop an
animated video to disseminate research findings. A 13-minute long whiteboard
animation video was produced from a research study about changing environments in
northern Canadian communities and was distributed to local people. Three
challenging issues in the video creation process including communication issues,
technical difficulties and contextual debate were resolved among the supporting
agencies and researchers. Conclusions Dissemination of findings is a crucial step
in the research process. Whiteboard animation video products may be a viable and
culturally-appropriate form of relaying research results back to Indigenous
communities in a storytelling format.
PMID- 28417786
TI - Changing of the guards.
PMID- 28417785
TI - Seasonal variation in affective and other clinical symptoms among high-risk
families for bipolar disorders in an Arctic population.
AB - Background In bipolar disorder (BD), seasonality of symptoms is common and
disturbances in circadian rhythms have been reported. Objectives We identified
high-penetrance families in a geographically restricted area in Northern
Fennoscandia and studied the seasonal variation of clinical symptoms among BD
subjects and their healthy relatives. Design We explored the clinical
characteristics of subjects living in Northern Fennoscandia, with extreme annual
variation in daylight. Among known indigenous high-risk families for BD, we
compared the affected ones (N=16) with their healthy relatives (N=15), and also
included 18 healthy non-related controls from the same geographical area.
Seasonal fluctuation in clinical measures was followed up at the 4 most
demarcated photoperiodic time points of the annual cycle: around the summer
solstice and autumn equinox in 2013, the winter solstice in 2013/2014, and the
spring equinox in 2014. In the baseline, lifetime manic symptoms [Mood Disorder
Questionnaire (MDQ)] and morningness-eveningness questionnaire type (MEQ) were
registered, whereas in the follow-up, depressive [Beck Depression Inventory
(BDI)] and distress [General Health Questionnaire (GHQ-12)] symptoms and alcohol
consumption and sleep were recorded. Results Possibly indicative or statistically
significant differences in symptoms between the affected subjects and their
healthy relatives were the BDI winter (13.3 vs. 2.6, t=-2.51, p=0.022) and spring
scores (12.6 vs. 3.2, t=-1.97, p=0.063) and GHQ winter (4.2 vs. 0.82, t=-2.08,
p=0.052) and spring scores (3.8 vs. 0.82, t=-1.97, p=0.063). Scores were higher
among the affected subjects, exceeding a possibly diagnostic threshold (10 and 3)
at all the time points, and without the notable seasonality which was observed
among the healthy relatives. In the overall population, MDQ and MEQ scores had an
inverse correlation (-0.384, significant at 0.016), indicating increased lifetime
manic behaviour among "the night owl" chronotype subjects. Conclusions In an
Arctic population sample, we found different seasonal fluctuation in mood and
distress symptoms and sleep duration scores between subjects with bipolar
spectrum disorders and their healthy relatives. Despite the relatively small
sample size, the results indicate that the symptoms and signs of BD relate to a
disturbance in seasonal variation. Seasonal variation can be considered as an
interesting endophenotype for BD and a promising target for further genetic
studies.
PMID- 28417787
TI - What students do schools allocate to a cognitive-behavioural intervention?
Characteristics of adolescent participants in Northern Sweden.
AB - Background Adolescents are a vulnerable group when it comes to the risk of
developing depression. Preventing the onset of depressive episodes in this group
is therefore a major public health priority. In the last decades, school-based
cognitive-behavioural interventions have been a common primary prevention
approach. However, evidence on what girls actually are allocated to such
interventions when no researchers are involved is scarce. Objective To explore
how a selective cognitive-behavioural program (Depression In Swedish Adolescents)
developed to prevent depression in adolescents, was implemented in a naturalistic
setting in schools in northern part of Sweden. The focus was on characteristics
of participants allocated to the intervention. Design Cross-sectional baseline
data on depressive symptoms, school environment and socio-economic factors were
collected in 2011 by means of questionnaires in schools in a municipality in the
northern part of Sweden. Intervention participants were identified in a follow-up
questionnaire in 2012. Students (n=288) included in the analyses were in the ages
of 14-15. Results Sixty-six girls and no boys were identified as intervention
participants. They reported higher levels of depressive symptoms, lower personal
relative affluence, more sexual harassment victimization and less peer support
compared to female non-participants (n=222). Intervention participants were more
likely to attend schools with a higher proportion of low parental education
levels and a lower proportion of students graduating with a diploma. Conclusions
The developers of the intervention originally intended the program to be
universal or selective, but it was implemented as targeted in these schools. It
is important for school administrations to adhere to program fidelity when it
comes to what students it is aimed for. Implications for effectivenss trials of
cognitive-behavioural interventions in the school setting is discussed.
PMID- 28417788
TI - A scoping review of Indigenous suicide prevention in circumpolar regions.
AB - Background Suicide is a serious public health challenge in circumpolar regions,
especially among Indigenous youth. Indigenous communities, government agencies
and health care providers are making concerted efforts to reduce the burden of
suicide and strengthen protective factors for individuals, families and
communities. The persistence of suicide has made it clear that more needs to be
done. Objective Our aim was to undertake a scoping review of the peer-reviewed
literature on suicide prevention and interventions in Indigenous communities
across the circumpolar north. Our objective was to determine the extent and types
of interventions that have been reported during past decade. We want to use this
knowledge to support community initiative and inform intervention development and
evaluation. Design We conducted a scoping review of online databases to identify
studies published between 2004 and 2014. We included articles that described
interventions in differentiated circumpolar Indigenous populations and provided
evaluation data. We retained grey literature publications for comparative
reference. Results Our search identified 95 articles that focused on suicide in
distinct circumpolar Indigenous populations; 19 articles discussed specific
suicide-related interventions and 7 of these described program evaluation methods
and results in detail. The majority of publications on specific interventions
were found in North American countries. The majority of prevention or
intervention documentation was found in supporting grey literature sources.
Conclusion Despite widespread concern about suicide in the circumpolar world and
active community efforts to promote resilience and mental well-being, we found
few recorded programs or initiatives documented in the peer-reviewed literature,
and even fewer focusing specifically on youth intervention. The interventions
described in the studies we found had diverse program designs and content, and
used varied evaluation methods and outcomes. The studies we included consistently
reported that it was important to use community-based and culturally guided
interventions and evaluations. This article summarizes the current climate of
Indigenous circumpolar suicide research in the context of intervention and
highlights how intervention-based outcomes have largely remained outside of peer
reviewed sources in this region of the world.
PMID- 28417789
TI - Suicide in circumpolar regions: an introduction and overview.
AB - This extended editorial introduces the Special Issue on Suicide and Resilience in
Circumpolar Regions, the results of the knowledge synthesis project by an
international research team funded by the Canadian Institutes of Health Research
and endorsed by the Arctic Council. It focuses on the extent and magnitude of the
problem of suicidal behaviours and thoughts from a circumpolar perspective - the
variation across Arctic States and their northern regions, the excess risk among
some indigenous groups and their demographic characteristics. Much remains to be
learned about the design and implementation of youth-focused intervention
programmes, especially in a circumpolar comparative framework.
PMID- 28417790
TI - "We are like lemmings": making sense of the cultural meaning(s) of suicide among
the indigenous Sami in Sweden.
AB - Background Suicide is a widespread problem among indigenous people residing in
the circumpolar Arctic. Though the situation among the indigenous Sami in
northern Scandinavia is better than among some other indigenous people, suicide
is still regarded as a major public health issue. To adapt prevention strategies
that are culturally attuned one must understand how suicide is understood within
context. That is, the cultural meaning(s) of suicide. Objective To explore and
make sense of the cultural meaning(s) of suicide among Sami in Sweden. Design
Open-ended focus group discussions (FGDs) on the topic "suicide among Sami" were
carried out in 5 Sami communities in Sweden, with in total 22 strategically
selected Sami participants. FGDs were recorded, transcribed verbatim and analyzed
through employing content analysis. Results From the FGDs 4 themes emerged
including "The Sami are fighting for their culture and the herders are in the
middle of the fight," "Suicide as a consequence of Sami losing (or having lost)
their identity," "A wildfire in the Sami world" and "Difficult to get help as a
Sami." Conclusions Findings indicate that Sami in Sweden make sense of suicide in
relation to power and identity within a threatened Sami cultural context. Suicide
is then understood as an act that takes place and makes sense to others when a
Sami no longer has the power to maintain a Sami identity, resulting in being
disconnected from the Sami world and placed in an existential void where suicide
is a solution. The findings are useful in development of culturally attuned
suicide prevention among Sami in Sweden.
PMID- 28417791
TI - Effect evaluation of a heated ambulance mattress-prototype on thermal comfort and
patients' temperatures in prehospital emergency care - an intervention study.
AB - Background The ambulance milieu does not offer good thermal comfort to patients
during the cold Swedish winters. Patients' exposure to cold temperatures combined
with a cold ambulance mattress seems to be the major factor leading to an overall
sensation of discomfort. There is little research on the effect of active heat
delivered from underneath in ambulance care. Therefore, the aim of this study was
to evaluate the effect of an electrically heated ambulance mattress-prototype on
thermal comfort and patients' temperatures in the prehospital emergency care.
Methods A quantitative intervention study on ambulance care was conducted in the
north of Sweden. The ambulance used for the intervention group (n=30) was
equipped with an electrically heated mattress on the regular ambulance stretcher
whereas for the control group (n=30) no active heat was provided on the
stretcher. Outcome variables were measured as thermal comfort on the Cold
Discomfort Scale (CDS), subjective comments on cold experiences, and finger, ear
and air temperatures. Results Thermal comfort, measured by CDS, improved during
the ambulance transport to the emergency department in the intervention group
(p=0.001) but decreased in the control group (p=0.014). A significant higher
proportion (57%) of the control group rated the stretcher as cold to lie down
compared to the intervention group (3%, p<0.001). At arrival, finger, ear and
compartment air temperature showed no statistical significant difference between
groups. Mean transport time was approximately 15 minutes. Conclusions The use of
active heat from underneath increases the patients' thermal comfort and may
prevent the negative consequences of cold stress.
PMID- 28417792
TI - Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation
population with endemic tuberculosis.
AB - Background Canadian First Nation populations have experienced endemic and
epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host
defence peptide LL-37 is known to enhance control of pathogens such as
Mycobacterium tuberculosis. Objective Evaluate associations between serum levels
of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation
participants (N = 34) and assess correlations with single nucleotide
polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding
protein (VDBP). Design Venous blood was collected from all participants at
baseline (winter and summer) and in conjunction with taking vitamin D supplements
(1,000 IU/day) (winter and summer). Samples were analysed using ELISA for
concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were
genotyped. Results Circulating levels of 25(OH)D were not altered by vitamin D
supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs
did not correlate with serum concentrations of 25(OH)D, but LL-37 levels
significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR
SNP Bsm1 T/T genotypes. Conclusions Our findings suggest that vitamin D
supplementation may not be beneficial as an intervention to boost innate immune
resistance to M. tuberculosis in the Dene population.
PMID- 28417793
TI - Guideline concordant detection and management of depression among Alaska Native
and American Indian people in primary care.
AB - Background A tribal health organization in Alaska implemented a primary care
depression screening, detection and management initiative amongst 55,000 Alaska
Native/American Indian people (AN/AIs). Objectives (a) To describe the proportion
of AN/AIs screening positive for depression with depression noted or diagnosed
and proportion with guideline concordant management and (b) to assess whether
management varied by patient and provider factors. Research design Secondary
analysis of electronic and paper medical record information of 400 AN/AIs.
Measures Provider variables, patient demographics and patient clinical factors
were electronically queried. Manual chart audits assessed depression notation,
diagnoses and management within 12 weeks of positive screening. Multilevel
ordinal logistic modelling assessed management by patient and provider factors.
Results A depression diagnosis was present in 141 (35%) charts and 151 (38%) had
depressive symptoms noted. Detection was higher among AN/AIs with moderate and
severe depression (p<0.001). In total, 258 patients (66%) received guideline
concordant management, 32 (8%) had some management, and 110 (28%) received no
management. Younger patient age and increased provider tenure increased odds of
management. Conclusions Most AN/AIs screening positive for depression received
initial guideline concordant management. Additional outreach to older patients
and additional support for providers newer to practices appears warranted.
PMID- 28417794
TI - Assessing health care in Canada's North: what can we learn from national and
regional surveys?
AB - Background Health surveys are a rich source of information on a variety of health
issues, including health care. Objectives This article compares various national
and regional surveys in terms of their geographical coverage with respect to the
Canadian North, especially their Aboriginal population, and the comparability of
the survey contents relating to health care. Methods Three surveys were selected
as providing some information on health care, with separate estimates for the
North and its Aboriginal populations. They are the Canadian Community Health
Survey (CCHS), Aboriginal Peoples Survey (APS) and the First Nations Regional
Health Survey (RHS). Results Different surveys focus on different categories of
Aboriginal people, and no single survey has covered all categories of Aboriginal
people in the North consistently. RHS is targeted at the on-reserve First Nations
population only. APS and CCHS sample the off-reserve First Nations population as
well as Metis and Inuit. To achieve adequate sample size for North-South
comparisons and comparisons among Aboriginal groups within the North, several
cycles of the biennial/annual CCHS can be merged, producing a large data set with
consistent coverage of topics using comparable questions. The content areas of
the 3 surveys can be broadly categorized as health status, health determinants
and health care. Substantial variation exists across surveys in the domains
covered. There are also changes over time in terms of definitions, questions and
even basic concepts. The available health care content of the 3 surveys focus on
access to different types of health services, contact with different categories
of health professionals, unmet health needs and the use of preventive services.
Many important dimensions of health care are not covered. Not all these basic
indicators are available for the North or its Aboriginal populations. Conclusions
A comprehensive survey of health care in the North with sufficient sample size to
provide reliable estimates for its subpopulations - urban and remote, Aboriginal
and non-Aboriginal, and First Nations, Inuit and Metis - would provide useful
information to decision-makers and service providers. Analytical studies can also
be conducted to investigate the correlations and interactions among health
status, health determinants and health care and assess whether such relationships
differ among the different population groups.
PMID- 28417795
TI - Sexual and reproductive health in Greenland: evaluation of implementing sexual
peer-to-peer education in Greenland (the SexInuk project).
AB - Background For decades, the rates of sexually transmitted infections (STIs), such
as gonorrhoea, chlamydia and syphilis, have increased in Greenland, especially
within the young age groups (15-29 years). From 2006 to 2013, the number of
abortions has been consistent with approximately 800-900 abortions per year in
Greenland, which is nearly as high as the total number of births during the same
period. Previous studies in Greenland have reported that knowledge about sexual
health is important, both as prevention and as facilitator to stop the increasing
rates of STIs. A peer-to-peer education programme about sexual health requires
adaption to cultural values and acceptance among the population and government in
order to be sustainable. Objective Formative evaluation of a voluntary project
(SexInuk), in relation to peer-to-peer education with focus on sexual health. Two
workshops were conducted in Nuuk, Greenland, to recruit Greenlandic students.
Design Qualitative design with focus group interviews (FGIs) to collect
qualitative feedback on feasibility and implementation of the project.
Supplemented with a brief questionnaire regarding personal information (gender,
age, education) and questions about the educational elements in the SexInuk
project. Eight Greenlandic students, who had completed one or two workshops, were
enrolled. Results The FGIs showed an overall consensus regarding the need for
improving sexual health education in Greenland. The participants requested more
voluntary educators, to secure sustainability. The articulation of taboo topics
in the Greenlandic society appeared very important. The participants suggested
more awareness by promoting the project. Conclusion Cultural values and language
directions were important elements in the FGIs. To our knowledge, voluntary work
regarding peer-to-peer education and sexual health has not been structurally
evaluated in Greenland before. To achieve sustainability, the project needs
educators and financial support. Further research is needed to investigate how
peer-to-peer education can improve sexual and reproductive health in Greenland.
PMID- 28417796
TI - Patterns of youth injury: a comparison across the northern territories and other
parts of Canada.
AB - Background Injury is the leading cause of death for young people in Canada. For
those living in the northern territories (Yukon, Nunavut, and the Northwest
Territories), injury represents an even greater problem, with higher rates of
injury for people of all ages in northern areas compared with the rest of Canada;
however, no such comparative studies have focussed specifically on non-fatal
injury in youth. Objective To profile and examine injuries and their potential
causes among youth in the northern territories as compared with other parts of
Canada. Design Cross-sectional data from the 2009/2010 Health Behaviour in School
aged Children survey (youth aged 11-15 years) were examined for the Canadian
northern territories and the provinces (n=26,078). Individual survey records were
linked to community-level data to profile injuries and then study possible
determinants via multilevel regression modelling. Results The prevalence of
injury reported by youth was similar in northern populations and other parts of
Canada. There were some minimal differences by injury type: northern youth
experienced a greater percentage of neighbourhood (p<0.001) and fighting (p=0.02)
injuries; youth in the Canadian provinces had a greater proportion of sport
related injuries (p=0.01). Among northern youth, female sex (RR=0.87, 95% CI 0.81
0.94), average (RR=0.88, 95% CI 0.80-0.97) or above-average affluence (RR=0.84,
95% CI 0.76-0.91), not being drunk in the past 12 months (RR=0.77, 95% CI 0.69
0.85), not riding an all-terrain vehicle (RR=0.81, 95% CI 0.68-0.97) and not
having permanent road access (RR=0.89, 95% CI 0.80-0.98) were protective against
injury; sport participation increased risk (RR=1.45, 95% CI 1.33-1.59).
Conclusions Patterns of injury were similar across youth from the North and other
parts of Canada. Given previous research, this was unexpected. When implementing
injury prevention initiatives, individual and community-level risk factors are
essential to understand; however, specific positive safety assets that might
exist in different community contexts must also be considered.
PMID- 28417797
TI - Prevalence of self-reported stomach symptoms after consuming milk among
indigenous Sami and non-Sami in Northern- and Mid-Norway - the SAMINOR study.
AB - Objective The main purpose of this work was to identify the prevalence of self
reported stomach symptoms after consuming milk among Sami and non-Sami adults.
Study design A cross-sectional population-based study (the SAMINOR study). Data
were collected by self-administrated questionnaires. Method SAMINOR is a
population-based study of health and living conditions conducted in 24
municipalities in Northern Norway during 2003 and 2004. The present study
included 15,546 individuals aged between 36 and 79, whose ethnicity was
categorized as Sami (33.4%), Kven (7.3%) and Norwegian majority population
(57.2%). Results Sami respondents had a higher prevalence of self-reported
stomach symptoms after consuming milk than the Norwegian majority population. The
reporting was highest among Sami females (27.1%). Consumption of milk and dairy
products (yoghurt and cheese) was high among all the ethnic groups. However,
significantly more Sami than non-Sami never (or rarely) consume milk or cheese,
and individuals who reported stomach symptoms after consuming milk had an
significant lower intake of dairy products than those not reporting stomach
symptoms after consuming dairy products. Sami reported general abdominal pain
more often than the majority population. The adjusted models show a significant
effect of Sami ethnicity in both men and women on self-reported stomach symptoms
after consuming milk. In females, the odds ratio (OR)=1.77 (p=0.001) and in males
OR=1.64 (p=0.001). Conclusion Our study shows that the Sami population reported
more stomach symptoms after consuming milk, suggesting a higher prevalence of
milk intolerance among the Sami population than the Norwegian majority
population.
PMID- 28417798
TI - Ethnic discrimination and health: the relationship between experienced ethnic
discrimination and multiple health domains in Norway's rural Sami population.
AB - Objective Self-reported ethnic discrimination has been associated with a range of
health outcomes. This study builds on previous efforts to investigate the
prevalence of self-reported ethnic discrimination in the indigenous (Sami)
population, and how such discrimination may be associated with key health
indicators. Study design The study relies on data from the 2003/2004 (n=4,389)
population-based study of adults (aged 36-79 years) in 24 rural municipalities of
Central and North Norway (the SAMINOR study). Self-reported ethnic discrimination
was measured using the question: "Have you ever experienced discrimination due to
your ethnic background?" Health indicators included questions regarding
cardiovascular disease, diabetes, chronic muscle pain, metabolic syndrome and
obesity. Logistic regression was applied to examine the relationship between self
reported ethnic discrimination and health outcomes. Results The study finds that
for Sami people living in minority areas, self-reported ethnic discrimination is
associated with all the negative health indicators included in the study.
Conclusion We conclude that ethnic discrimination affects a wide range of health
outcomes. Our findings highlight the importance of ensuring freedom from
discrimination for the Sami people of Norway.
PMID- 28417799
TI - Continuum of care for persons with common mental health disorders in Nunavik: a
descriptive study.
AB - Background Changing Directions, Changing Lives, the Mental Health Strategy for
Canada, prioritizes the development of coordinated continuums of care in mental
health that will bridge the gap in services for Inuit populations. Objective In
order to target ways of improving the services provided in these contexts to
individuals in Nunavik with depression or anxiety disorders, this research
examines delays and disruptions in the continuum of care and clinical, individual
and organizational characteristics possibly associated with their occurrences.
Design A total of 155 episodes of care involving a common mental disorder (CMD),
incident or recurring, were documented using the clinical records of 79 frontline
health and social services (FHSSs) users, aged 14 years and older, living in a
community in Nunavik. Each episode of care was divided into 7 stages: (a)
detection; (b) assessment; (c) intervention; (d) planning the first follow-up
visit; (e) implementation of the first follow-up visit; (f) planning a second
follow-up visit; (g) implementation of the second follow-up visit. Sequential
analysis of these stages established delays for each one and helped identify when
breaks occurred in the continuum of care. Logistic and linear regression analysis
determined whether clinical, individual or organizational characteristics
influenced the breaks and delays. Results More than half (62%) the episodes of
care were interrupted before the second follow-up. These breaks mostly occurred
when planning and completing the first follow-up visit. Episodes of care were
more likely to end early when they involved anxiety disorders or symptoms,
limited FHSS teams and individuals over 21 years of age. The median delay for the
first follow-up visit (30 days) exceeded guideline recommendations significantly
(1-2 weeks). Conclusion Clinical primary care approaches for CMDs in Nunavik are
currently more reactive than preventive. This suggests that recovery services for
those affected are suboptimal.
PMID- 28417800
TI - Time trend by region of suicides and suicidal thoughts among Greenland Inuit.
AB - Background Suicides remain a major public health problem in Greenland. Their
increase coincides with the modernization since 1950. Serious suicidal thoughts
are reported by a significant proportion of participants in countrywide surveys.
Objective To analyze the time trend by region of suicides and suicidal thoughts
among the Inuit in Greenland. Design Data included the Greenland registry of
causes of death for 1970-2011 and 2 cross-sectional health surveys carried out in
1993-1994 and 2005-2010 with 1,580 and 3,102 Inuit participants, respectively.
Results Suicide rates were higher among men than women while the prevalence of
suicidal thoughts was higher among women. Suicide rates for men and women
together increased from 1960 to 1980 and have remained around 100 per 100,000
person-years since then. The regional pattern of time trend for suicide rates
varied with an early peak in the capital, a continued increase to very high rates
in remote East and North Greenland and a slow increase in villages relative to
towns on the West Coast. Suicidal thoughts followed the regional pattern for
completed suicides. Especially for women there was a noticeable increasing trend
in the villages. The relative risk for suicide was highest among those who
reported suicidal thoughts, but most suicides happened outside this high-risk
group. Conclusion Suicide rates and the prevalence of suicidal thoughts remain
high in Greenland but different regional trends point towards an increased
marginalization between towns on the central West Coast, villages and East and
North Greenland. Different temporal patterns call for different regional
strategies of prevention.
PMID- 28417801
TI - Ethical guidelines for Sami research: the issue that disappeared from the
Norwegian Sami Parliament's agenda?
AB - Background In recent decades many indigenous communities, policy makers and
researchers worldwide have criticized the academic community for not being aware
of the specific challenges these communities have faced and still are facing with
regard to research. One result of the decades of discourse in indigenous
communities is the development in many Western countries of indigenously
sensitive ethical research guidelines. In 1997 the Sami Parliament (SP) in Norway
reached a unanimous decision that ethical guidelines for Sami research had to be
drawn up. Such guidelines are however still to be created. Objectives The
objectives of this article are to enquire into what happened to the Norwegian
SP's decision of 1997 and to reflect on why the issue seems to have disappeared
from the SP's agenda. Finally, we consider whether research ethics is to be a
subject for the research community only. Methods A review of parliamentary white
papers on research and SP documents relating to research ethics. Findings The
response to the SP's decision in 1997 took place in two different channels, both
of them national, namely the research ethics channel and the political channel.
Thus, there were actually two parallel processes taking place. In spite of nearly
two decades of reports, the concept of the participation of indigenous
communities in research is still not an integral part of Norwegian ethical
guidelines. Conclusions The issue of indigenously sensitive research ethics seems
to have disappeared from the SP's agenda and the research ethics review system
with regard to Sami research is with minor adjustments the same as when the SP
asked for a revision.
PMID- 28417803
TI - Outbreak of eczema and rhinitis in a group of office workers in Greenland.
AB - Introduction Disturbed indoor climate may in some cases be associated with
illness. In the present paper, we report the results from a thorough
investigation of office workers in Greenland, who developed skin and/or airway
problems after moving into renewed offices. Material and methods In 2009 the
office of the Bank of Greenland had a total renovation of the building, including
new furniture and carpets. Symptoms developed within the first year after moving
back into the renewed buildings. After removal of carpets in the building,
symptoms significantly improved. Workers were examined in 2009 and re-examined in
2013, including clinical examination, patch test and when relevant also skin
prick tests and histamine release test. Isothiazolinones and fumarates, both able
to cause airway as well as skin symptoms, were isolated from carpets before
testing, and included in the test series. Results In total, 32 out of 80 workers
(40%) developed symptoms; 27 reported eczema, 20 rhinitis and 4 urticaria. Eczema
was located on the hands and/or lower arms in 18 workers, on the face in 10
workers and on legs/trunk in 12 workers. After intervention in the office, 22
workers with eczema reported significant improvement, all cases of hand eczema
cleared and 16 workers with rhinitis also improved. Positive patch tests to
carpet extracts were found significantly more frequent in the worker cohort than
in a control group comprising 47 dermatitis patients (p<0.001). Only few workers
reacted with a positive response to skin prick test or in the HR test, no obvious
pattern in reactions was found, and no conclusions can be made from these
reactions. Conclusion The results indicate that the reported symptoms are related
to exposures from the building after renovation in 2009. A specific triggering
exposure could not be identified, although chemicals from the glued carpets are
suspected. The study is an example of a work place investigation, and illustrates
the diversity of symptoms and exposures involved in "Sick Building" cases.
PMID- 28417804
TI - Conceptual understanding of social capital in a First Nations community: a social
determinant of oral health in children.
AB - Objective The purpose of the study was: (a) to better understand the concept of
social capital and its potential role in oral health of children in a First
Nations community and (b) to identify the strengths and resources in terms of
social capital and a health promotion model that the community has at its
disposal to address its oral health issues. Methods In this qualitative case
study, participants were purposively selected in a First Nations community: Seven
individual interviews and two focus groups involving 18 parents/care givers were
selected. Putnam's concept of social capital guided all the interviews. The
interviews were recorded and transcribed verbatim. Thematic analysis was employed
using the NVivo software. Results The community was close-knit and seemed to have
strong moral fibre, which encouraged members to help each other. A strong bonding
social capital was also found among the members, especially inside the clans
(families). A need for improvement in bridging social capital that would help the
community to reach external resources was observed. While members of the
community were actively involved in religious rituals and cultural ceremonies,
more efforts seemed to be required to recruit volunteers for other events or
programs. Active engagement of community members in any program requires that
members be given a voice as well as some ownership of the process. Mobilizing or
building community's social capital can play a role when planning future
interventions. Conclusion A better understanding of social capital may enhance
the community's investment and efforts by reinforcing healthy oral behaviours and
improving access to external resources. With more dynamic collaboration, it may
be possible to create more sustainable community-based oral health promotion
programs.
PMID- 28417805
TI - One Health - a strategy for resilience in a changing arctic.
AB - The circumpolar north is uniquely vulnerable to the health impacts of climate
change. While international Arctic collaboration on health has enhanced
partnerships and advanced the health of inhabitants, significant challenges lie
ahead. One Health is an approach that considers the connections between the
environment, plant, animal and human health. Understanding this is increasingly
critical in assessing the impact of global climate change on the health of Arctic
inhabitants. The effects of climate change are complex and difficult to predict
with certainty. Health risks include changes in the distribution of infectious
disease, expansion of zoonotic diseases and vectors, changing migration patterns,
impacts on food security and changes in water availability and quality, among
others. A regional network of diverse stakeholder and transdisciplinary
specialists from circumpolar nations and Indigenous groups can advance the
understanding of complex climate-driven health risks and provide community-based
strategies for early identification, prevention and adaption of health risks in
human, animals and environment. We propose a regional One Health approach for
assessing interactions at the Arctic human-animal-environment interface to
enhance the understanding of, and response to, the complexities of climate change
on the health of the Arctic inhabitants.
PMID- 28417806
TI - Partnering with Indigenous student co-researchers: improving research processes
and outcomes.
AB - Objective To examine the contribution of student co-researchers to a community
based participatory Photovoice investigation of Indigenous children's food
related lived experience. We examine co-researchers' contributions to the
research process, their role in knowledge co-generation and dissemination, and
factors that fostered research partnership with the teenage co-researchers.
Methods High school students attending a First Nation community school in Canada
were trained as research partners. They contributed to aspects of research
design, conducted interviews with grades 3 and 4 Photovoice participants, and
participated in data analysis and the development of a culturally relevant
photobook. The study was initiated by the community's research committee. It is
informed by critical consciousness theory and the positive youth development
framework. Results Student co-researchers incorporated culturally appropriate
strategies as they interviewed participants. Co-researchers adopted
conversational approaches, built rapport by articulating personal and cultural
connections, and engaged in mentoring and health promotion as they interviewed
participants. They made critical contributions to dissemination by developing
photobook content that promoted the importance of traditional foods and the vital
role of family and community in healthy eating practices. Relationships and
"dialogic" space were important to building partnership with and promoting
capacity development among youth co-researchers. Conclusions Partnership between
university researchers and Indigenous student co-researchers holds great promise
for health promotion in communities. Co-researchers developed research and
leadership skills, gained understanding of health challenges facing their
community, and initiated health and cultural promotion through the project's
Photobook. This investigation supports the powerful potential of student co
researchers to meaningfully contribute to research processes and to build
knowledge that is relevant and credible both within and outside of their
communities. Findings have implications for youth, communities and researchers.
PMID- 28417807
TI - Incident diabetes, hypertension and dyslipidemia in a Manitoba First Nation.
AB - Background Diabetes and diabetes complications are substantially higher among
Canadian First Nations populations compared with the general Canadian population.
However, incidence data using detailed individual assessments from a population
based cohort have not been undertaken. Objective We sought to describe incident
diabetes, hypertension and dyslipidemia in a population-based cohort from a
Manitoba Ojibway First Nation community. Design Study data were from 2 diabetes
screening studies in Sandy Bay First Nation in Manitoba, Canada, collected in
2002/2003 and 2011/2012. The cohort comprised of respondents to both screening
studies (n=171). Health and demographic data were collected using a
questionnaire. Fasting blood samples, blood pressure and anthropometric data were
also collected objectively. Incident diabetes, hypertension and dyslipidemia were
determined. Generalized linear models with Poisson distribution were used to
estimate risk of incident diabetes and cardiometabolic conditions according to
age and sex. Results There were 35 (95% CI: 26, 45) new cases of diabetes among
128 participants without diabetes at baseline (27 or 3.3% per year). While
participants who were 50 years and older at baseline had a significantly higher
risk of incident diabetes at follow-up compared with participants aged 18-29 at
baseline (p=0.012), more than half of the incident cases of diabetes occurred
among participants aged less than 40 at baseline. There were 28 (95% CI: 20, 37)
new cases of dyslipidemia at follow-up among 112 without dyslipidemia at baseline
(25%). There were 36 (95% CI: 31, 42) new cases of hypertension among 104
participants without hypertension at baseline (34.6%). Women had half the risk of
developing hypertension compared with men (p=0.039). Conclusions Diabetes
incidence is very high, and the number of new cases among those younger than 40
is a concern. Additional public health and primary care efforts are needed to
address the diabetes burden in this First Nation community.
PMID- 28417808
TI - Development and evaluation of a support program for prostate cancer survivors in
Alaska.
AB - Background Prostate cancer survivors in Alaska and elsewhere have unmet support
needs. The Men's Prostate Cancer Survivorship Retreat, or "men's retreat," was
developed targeting Alaska Native and non-Native men who were survivors of
prostate cancer. The program brought together survivors in a supportive
environment to discuss and share their experiences. Objective Despite the proven
effectiveness of support groups for improving quality of life for cancer
patients, men typically do not participate in formal support groups. This
descriptive study was conducted to explore the needs of Alaska Native and non
Native prostate cancer survivors and assess satisfaction and acceptability of a
men's cancer survivorship retreat in Alaska. Methods Prostate cancer survivors
(N=80) who attended men's retreats during 2009-2013 were asked to complete a
retreat application and post-retreat evaluation. Comments regarding social
support, helpful and valuable aspects of the retreat including overall
satisfaction were reported. Results A men's retreat with activities that engage
men can be successful for prostate cancer survivors. Many men returned for
successive retreats. After the retreat, 97% of the participants said they would
continue with support activities. Conclusion The men's retreat provides a valued
opportunity for men to interact with other survivors and access information from
health professionals. The results from this study highlight a successful model
for social support and resources specific to male prostate cancer survivors.
PMID- 28417809
TI - Prevalence and molecular characterization of Cryptosporidium spp. and Giardia
duodenalis in diarrhoeic patients in the Qikiqtani Region, Nunavut, Canada.
AB - Background Although the prevalences of infection with the protozoan parasites
Cryptosporidium spp. and Giardia duodenalis in humans appear to be relatively
high in the Canadian North, their transmission patterns are poorly understood.
Objective To determine the detection rate and the molecular characteristics of
Cryptosporidium spp. and Giardia duodenalis in diarrhoeic patients in the
Qikiqtani (Baffin Island) Region of Nunavut, Canada, in order to better
understand the burden of illness and the potential mechanisms of transmission.
Study design/methods Diarrhoeal stool specimens (n=108) submitted to the
Qikiqtani General Hospital for clinical testing were also tested for the presence
of Cryptosporidium spp. and Giardia duodenalis using epifluorescence microscopy
and polymerase chain reaction (PCR). DNA sequencing and restriction fragment
length polymorphism (RFLP) analyses were performed on PCR-positive specimens to
determine the species, genotypes and sub-genotypes of the parasites. Results
Cryptosporidium was detected in 15.7% of the diarrhoeic patients, while Giardia
was detected in 4.6%. DNA sequencing of a fragment of the small subunit rRNA gene
indicated that all of the Cryptosporidium amplicons had a 100% homology to C.
parvum, and a gp60 assay showed that all aligned with C. parvum sub-genotype IIa.
Microsatellite analysis revealed 3 cases of sub-genotype IIaA15G2R1, 2 of
IIaA15G1R and 1 case each of sub-genotypes IIaA16G1R1 and IIaA15R1. For Giardia,
results based on the amplification of both the 16S rRNA gene and the gdh gene
were generally in agreement, and both DNA sequencing and RFLP demonstrated the
presence of the G. duodenalis Assemblage B genotype. Conclusions Both C. parvum
and G. duodenalis Assemblage B were present in human diarrhoeal stool specimens
from Nunavut, which was suggestive of zoonotic transmission, although human-to
human transmission cannot be ruled out. To fully understand the public health
significance of the different Cryptosporidium and Giardia species and genotypes
in diarrhoeic patients, it will be imperative to establish the extent of genetic
diversity within these parasites through comprehensive studies of the molecular
epidemiology of cryptosporidiosis and giardiasis in the Nunavut region.
PMID- 28417810
TI - Approaching Etuaptmumk - introducing a consensus-based mixed method for health
services research.
AB - With the recognized need for health systems' improvements in the circumpolar and
indigenous context, there has been a call to expand the research agenda across
all sectors influencing wellness and to recognize academic and indigenous
knowledge through the research process. Despite being recognized as a distinct
body of knowledge in international forums and across indigenous groups, examples
of methods and theories based on indigenous knowledge are not well documented in
academic texts or peer-reviewed literature on health systems. This paper
describes the use of a consensus-based, mixed method with indigenous knowledge by
an experienced group of researchers and indigenous knowledge holders who
collaborated on a study that explored indigenous values underlying health systems
stewardship. The method is built on the principles of Etuaptmumk or two-eyed
seeing, which aim to respond to and resolve the inherent conflicts between
indigenous ways of knowing and the scientific inquiry that informs the evidence
base in health care. Mixed methods' frameworks appear to provide a framing
suitable for research questions that require data from indigenous knowledge
sources and western knowledge. The nominal consensus method, as a western
paradigm, was found to be responsive to embedding of indigenous knowledge and
allowed space to express multiple perspectives and reach consensus on the
question at hand. Further utilization and critical evaluation of this mixed
methodology with indigenous knowledge are required.
PMID- 28417811
TI - Trajectories of women's homelessness in Canada's 3 northern territories.
AB - Background Repairing the Holes in the Net was a 2-year, multilevel action
research project designed to inform the development of culturally appropriate and
gender-specific services for northern women who are homeless or marginally housed
and who face mental health and substance use concerns. The study was designed to
learn about the barriers and supports experienced by homeless women in the North
when accessing mental health care, shelter, housing and other services; and to
inform the work of northern service providers and policy advocates in a position
to implement adjustments in their praxis. Methods This article describes the
trajectories of women's service access and their ideas for service improvement
from 61 qualitative, semi-structured interviews conducted with homeless women in
Whitehorse, Yukon (YT), Yellowknife, Northwest Territories (NT), and Iqualit,
Nunavut (NU). Results Unresolved trauma, poverty and social exclusion, inability
to find and maintain housing and ineffective services emerged as interconnected
and multifaceted challenges related to women's service engagement. In the face of
these challenges, women displayed significant resilience and resistance, and
offered important ideas for service improvement. Conclusions The 4 interconnected
systemic challenges identified in the research, coupled with specific ideas for
change cited by the resilient homeless women interviewed, offer points of entry
to improve service policy and delivery. Implementing trauma-informed approaches
emerged as a key example of how access to, and quality of, services could be
improved for homeless women in the North.
PMID- 28417812
TI - Air ambulance and hospital services for critically ill and injured in Greenland,
Iceland and the Faroe Islands: how can we improve?
AB - The Nordic Atlantic Cooperation (NORA) is an intergovernmental organization under
the auspices of the Nordic Council of Ministers. The NORA region comprises
Greenland, Iceland, Faroe Islands and western coastal areas of Norway.
Historical, cultural and institutional links bind these nations together in
multiple ways, and regional co-operation has in recent years become a focus of
interest. This commentary addresses air medical services (AMSs) and available
advanced hospital services in the 3 smallest NORA countries challenged sparse
populations, hereafter referred to as the region. It seems likely that
strengthened regional co-operation can help these countries to address common
challenges within health care by exchanging know-how and best practices, pooling
resources and improving the efficiency of care delivery. The 4 largest hospitals
in the region, Dronning Ingrids Hospital in Nuuk (Greenland), Landspitali in
Reykjavik and Sjukrahusid a Akureyri, (both in Iceland) and Landssjukrahusid
Torshavn on the Faroe Islands, have therefore undertaken the project Network for
patient transport in the North-West Atlantic (in Danish: Netvaerk for
patienttransport i Vest-Norden). The goal of the project, and of this article, is
to exchange information and provide an overview of current AMSs and access to
acute hospital care for severely ill or injured patients in the 3 participating
countries. Of equal importance is the intention to highlight the need for
increased regional co-operation to optimize use of limited resources in the
provision of health care services.
PMID- 28417813
TI - Human exposure to soil contaminants in subarctic Ontario, Canada.
AB - Background Chemical contaminants in the Canadian subarctic present a health risk
with exposures primarily occurring via the food consumption. Objective
Characterization of soil contaminants is needed in northern Canada due to
increased gardening and agricultural food security initiatives and the presence
of known point sources of pollution. Design A field study was conducted in the
western James Bay Region of Ontario, Canada, to examine the concentrations of
polychlorinated biphenyls, dichlorodiphenyltrichloroethane and its metabolites
(SigmaDDT), other organochlorines, and metals/metalloids in potentially
contaminated agriculture sites. Methods Exposure pathways were assessed by
comparing the estimated daily intake to acceptable daily intake values. Ninety
soil samples were collected at random (grid sampling) from 3 plots (A, B, and C)
in Fort Albany (on the mainland), subarctic Ontario, Canada. The contaminated
soil samples were analysed by gas chromatography with an electron capture
detector or inductively coupled plasma mass spectrometer. Results The range of
SigmaDDT in 90 soil samples was below the limit of detection to 4.19 mg/kg. From
the 3 soil plots analysed, Plot A had the highest SigmaDDT mean concentration of
1.12 mg/kg, followed by Plot B and Plot C which had 0.09 and 0.01 mg/kg,
respectively. Concentrations of other organic contaminants and metals in the soil
samples were below the limit of detection or found in low concentrations in all
plots and did not present a human health risk. Conclusions Exposure analyses
showed that the human risk was below regulatory thresholds. However, the SigmaDDT
concentration in Plot A exceeded soil guidelines set out by the Canadian Council
of Ministers of the Environment of 0.7 mg/kg, and thus the land should not be
used for agricultural or recreational purposes. Both Plots B and C were below
threshold limits, and this land can be used for agricultural purposes.
PMID- 28417814
TI - Lower respiratory tract infection hospitalizations among American Indian/Alaska
Native children and the general United States child population.
AB - Background The lower respiratory tract infection (LRTI)-associated
hospitalization rate in American Indian and Alaska Native (AI/AN) children aged
<5 years declined during 1998-2008, yet remained 1.6 times higher than the
general US child population in 2006-2008. Purpose Describe the change in LRTI
associated hospitalization rates for AI/AN children and for the general US child
population aged <5 years. Methods A retrospective analysis of hospitalizations
with discharge ICD-9-CM codes for LRTI for AI/AN children and for the general US
child population <5 years during 2009-2011 was conducted using Indian Health
Service direct and contract care inpatient data and the Nationwide Inpatient
Sample, respectively. We calculated hospitalization rates and made comparisons to
previously published 1998-1999 rates prior to pneumococcal conjugate vaccine
introduction. Results The average annual LRTI-associated hospitalization rate
declined from 1998-1999 to 2009-2011 in AI/AN (35%, p<0.01) and the general US
child population (19%, SE: 4.5%, p<0.01). The 2009-2011 AI/AN child average
annual LRTI-associated hospitalization rate was 20.7 per 1,000, 1.5 times higher
than the US child rate (13.7 95% CI: 12.6-14.8). The Alaska (38.9) and Southwest
regions (27.3) had the highest rates. The disparity was greatest for infant (<1
year) pneumonia-associated and 2009-2010 H1N1 influenza-associated
hospitalizations. Conclusions Although the LRTI-associated hospitalization rate
declined, the 2009-2011 AI/AN child rate remained higher than the US child rate,
especially in the Alaska and Southwest regions. The residual disparity is likely
multi-factorial and partly related to household crowding, indoor smoke exposure,
lack of piped water and poverty. Implementation of interventions proven to reduce
LRTI is needed among AI/AN children.
PMID- 28417816
TI - Primary health care accessibility challenges in remote indigenous communities in
Canada's North.
AB - Background Despite many improvements, health disparities between indigenous and
non-indigenous populations in Canada's North persist. While a strong primary
health care (PHC) system improves the health of a population, the majority of
indigenous communities are very remote, and their access to PHC services is
likely reduced. Understanding the challenges in accessing PHC services in these
communities is necessary to improve the health of the population. Objective The
objective of the study was to document and analyze the challenges in accessing
PHC services by indigenous people in remote communities in Canada's Northwest
Territories (NWT) from the perspectives of users and providers of PHC services.
Methods Using explorative, qualitative methods, our study involved 14 semi
structured interviews with PHC service providers (SPs) and service users (SUs) in
5 communities across the NWT which varied according to population, remoteness,
ethnic composition and health care resources. The interview guide was developed
after key informant consultations. Results Both SPs and SUs understood the
constraints in providing equitable access to PHC services in remote communities.
The provision of emergency care was found to be particularly challenging, because
of the lack of qualified staff in the community and the dependence on aeromedical
evacuations. Wider dissemination of first aid skills among community members was
seen to cover some gaps and also increase self-confidence. For non-emergency
care, the need to travel outside the community was generally disliked. All
recognized the need for more preventive services which were often postponed or
delayed because of the overwhelming demand for acute care. As long as services
were provided in a community, the satisfaction was high among SUs. SPs
appreciated the orientation they received and the ability to build rapport with
the community. Conclusions Northern SUs and SPs generally acknowledge the health
consequences of living in remote communities. The generally high level of
satisfaction attests to the overall effectiveness of PHC in the region despite
geographical remoteness. Many improvements could be made in terms of upgrading
the clinical skills of SPs and community members, improving staff retention,
extending the frequency and duration of community visits and providing more
attention to preventive services.
PMID- 28417817
TI - Views on electronic cigarette use in tobacco screening and cessation in an Alaska
Native healthcare setting.
AB - Background American Indian (AI) and Alaska Native (AN) communities confront some
of the highest rates of tobacco use and its sequelae. Methods This formative
research project sought to identify the perspectives of 41 stakeholders
(community members receiving care within the healthcare system, primary care
providers, and tribal healthcare system leaders) surrounding the use of
pharmacogenetics toward tobacco cessation treatment in the setting of an AI/AN
owned and operated health system in south central Alaska. Results Interviews were
held with 20 adult AI/AN current and former tobacco users, 12 healthcare
providers, and 9 tribal leaders. An emergent theme from data analysis was that
current tobacco screening and cessation efforts lack information on electronic
cigarette (e-cigarette) use. Perceptions of the use of e-cigarettes role in
tobacco cessation varied. Conclusion Preventive screening for tobacco use and
clinical cessation counseling should address e-cigarette use. Healthcare provider
tobacco cessation messaging should similarly address e-cigarettes.
PMID- 28417818
TI - Evaluation of the K[Formula: see text]ts'iihtla ("We Light the Fire") Project:
building resiliency and connections through strengths-based creative arts
programming for Indigenous youth.
AB - Background The creative arts - music, film, visual arts, dance, theatre, spoken
word, literature, among others - are gradually being recognised as effective
health promotion tools to empower, engage and improve the health and well-being
in Indigenous youth communities. Arts-based programming has also had positive
impacts in promoting health, mental wellness and resiliency amongst youth.
However, often times the impacts and successes of such programming are not
formally reported on, as reflected by the paucity of evaluations and reports in
the literature. Objective The objective of this study was to evaluate a creative
arts workshop for Tlicho youth where youth explored critical community issues and
found solutions together using the arts. We sought to identify the workshop's
areas of success and challenge. Ultimately, our goal is to develop a community
led, youth-driven model to strengthen resiliency through youth engagement in the
arts in circumpolar regions. Design Using a mixed-methods approach, we conducted
observational field notes, focus groups, questionnaires, and reflective practice
to evaluate the workshop. Four youth and five facilitators participated in this
process overall. Results Youth reported gaining confidence and new skills, both
artistic and personal. Many youth found the workshop to be engaging, enjoyable
and culturally relevant. Youth expressed an interest in continuing their
involvement with the arts and spreading their messages through art to other youth
and others in their communities. Conclusions Engagement and participation in the
arts have the potential to build resiliency, form relationships, and stimulate
discussions for community change amongst youth living in the North.
PMID- 28417819
TI - Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae
strains in Nuuk, Greenland: time to reconsider preventive and treatment
strategies.
AB - Objectives Sexually transmitted infections (STIs), including infections with
Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011,
GC testing has been performed on urine with nucleic acid amplification tests
(NAATs) by strand displacement amplification (Becton Dickinson ProbeTec).
Monitoring of GC antibiotic susceptibility by culture was introduced in Nuuk in
2012. Until 2014, no cases of ciprofloxacin-resistant GC strains were reported.
In this paper, we report the finding of ciprofloxacin-resistant GC and describe
the most recent incidence of GC infections in Greenland. Methods The number of
urine NAATs and culture-positive swabs from January to October 2014 were obtained
from the Central Laboratory at Queens Ingrid's Hospital in Nuuk and stratified on
gender, place and period of testing. Incidence rates were estimated as number of
urine NAAT * (12/10) per 100,000 inhabitants. Men in Nuuk with a positive NAAT
for GC were encouraged to provide a urethral swab for culture and susceptibility
testing. Results From January to October 2014, a total of 5,436 urine GC NAATs
were performed on patients from Nuuk and 9,031 from the rest of Greenland. Of
these, 422 (8%) and 820 (9%) were positive, respectively. From January to August,
6 (15%) cultures from Nuuk were ciprofloxacin resistant while in September and
October, 26 (59%) were ciprofloxacin resistant (p<0.01). In total, 35 (40%) of 88
culture-positive isolates showed ciprofloxacin resistance. GC incidence in Nuuk
was 3,017 per 100,000 inhabitants per year, compared to 2,491 per 100,000
inhabitants per year in the rest of Greenland. Conclusion Within a short period,
a rapid and dramatic change in ciprofloxacin susceptibility among GC strains
isolated in Nuuk was documented and recommendation for first line treatments has
changed. Continued monitoring and rethinking of primary and secondary preventive
initiatives is highly recommended in this high GC incidence setting.
PMID- 28417820
TI - Dietary intakes of expeditioners during prolonged sunlight deprivation in polar
enviroments do not support bone health.
AB - Background Early Antarctic expeditions were plagued by nutrient deficiencies, due
to lack of fresh food and reliance on preserved foods. Modern Antarctic
expeditioners also require provisions to be shipped in, but improved knowledge
and storage options ensure foods are nutritionally sound. Despite this,
nutritional imbalances are observed. Objectives To determine the adequacy of
dietary intake of Antarctic expeditioners, with reference to bone health. Design
Dietary intake was determined on 225 adults (mean age 42+/-11 years, 16% female)
during 12-month deployments at Australian Antarctic stations from 2004 to 2010,
using weighed 3-day food records. Nutrient intake was analysed using FoodWorks.
Foods were divided into the 5 food groups according to the Australian Guide to
Healthy Eating. Results Men consumed below the recommended levels [recommended
daily intake (RDI)/adequate intakes (AI)] of calcium (79+/-42% of RDI, p<0.001),
magnesium (83+/-34% of RDI, p<0.001), potassium (86+/-29% of AI, p<0.001) and
fibre (75+/-30% of AI, p<0.001), and above the upper limit (UL) for sodium (125+/
48% of UL p<0.001), whereas women consumed below the recommended levels of
calcium (68+/-21% of RDI, p<0.001) and iron (73+/-37% of RDI, p<0.001). Vitamin D
intake is not substantial (<150 IU/d). Men consumed more alcohol than women (18+/
24 g/d vs. 10+/-13 g/d, p<0.05), nearer the guideline of <=20 g/d. Men and women
consumed approximately 1 serving of dairy food per day, and 3 of 5 recommended
vegetable servings. Discretionary foods were consumed in excess of recommended.
Conclusions Improving consumption of calcium-rich (dairy) foods better supports
bone health during sunlight deprivation. Increasing vegetable intake to
recommended levels will increase fibre, potassium and magnesium intakes. The
challenge is the logistics of providing these foods throughout the year.
PMID- 28417821
TI - What can we talk about, in which language, in what way and with whom? Sami
patients' experiences of language choice and cultural norms in mental health
treatment.
AB - Background The Sami in Norway have a legal right to receive health services
adapted to Sami language and culture. This calls for a study of the significance
of language choice and cultural norms in Sami patients' encounters with mental
health services. Objectives To explore the significance of language and cultural
norms in communication about mental health topics experienced by Sami patients
receiving mental health treatment to enhance our understanding of linguistic and
cultural adaptation of health services. Methods Data were collected through
individual interviews with 4 Sami patients receiving mental health treatment in
Northern Norway. A systematic text reduction and a thematic analysis were
employed. Findings Two themes were identified: (I) Language choice is influenced
by language competence, with whom one talks and what one talks about.
Bilingualism was a resource and natural part of the participants' lives, but
there were limited possibilities to speak Sami in encounters with health
services. A professional working relationship was placed on an equal footing with
the possibility to speak Sami. (II) Cultural norms influence what one talks
about, in what way and to whom. However, norms could be bypassed, by talking
about norm-regulated topics in Norwegian with health providers. Conclusion Sami
patients' language choice in different communication situations is influenced by
a complexity of social and cultural factors. Sami patients have varying opinions
about and preferences for what they can talk about, in which language, in what
way and with whom. Bilingualism and knowledge about both Sami and Norwegian
culture provide latitude and enhanced possibilities for both patients and the
health services. The challenge for the health services is to allow for and
safeguard such individual variations within the cultural framework of the
patients.
PMID- 28417822
TI - Lifestyle, reproductive factors and food intake in Greenlandic pregnant women:
The ACCEPT - sub-study.
AB - Background In the past decades, Greenland has changed from a hunter society to a
more western lifestyle, causing less intake of traditional food, such as marine
mammals, fish and seabirds. These changes in the living conditions and food
habits might impact the maternal health in Greenland. Objectives To describe
lifestyle, reproductive factors and food intake in Greenlandic pregnant women,
and to assess possible age and geographical differences. Design Cross-sectional
study of 189 Greenlandic pregnant women. Inclusion criteria were >=18 years and
lived >50% of their life in Greenland. Data were collected in 2010-2011, and
information was obtained from lifestyle and food frequency questionnaires. Two
age groups for comparison were given for the pregnant women (<27 years vs. >=27
years) with regard to the median age. Region groups for comparison were West,
Disko Bay, South, North and East. Results Population characteristics showed that
43.3% had pre-pregnancy body mass index (BMI) >25.0 kg/m2, 46.3% were current
smokers in the beginning of their pregnancy and few participants consumed alcohol
during pregnancy. Women <27 years were more in doubt regarding planned
breastfeeding period and consumed more dried fish and fast food. A trend for
higher alcohol intake during pregnancy was found for women >=27 years. The
regional differences showed that women living >50% in North, South and West had a
higher alcohol intake during pregnancy. Women in North had the fewest
breastfeeding plans. Women in Disko Bay had the lowest intake of terrestrial
species. No significant geographical differences were found for intake of marine
mammals or seabirds. Conclusions The present study found relatively high BMI
level and high smoking frequency in Greenlandic pregnant women. Age and region
differences were found for alcohol consumption, breastfeeding plans and food
intake profile. Further research is needed to implement relevant maternal health
intervention programs in Greenland.
PMID- 28417823
TI - Regional differences in renal replacement therapy in northern Norway 2000-2012.
AB - Objective Distance from residence location to a centre for renal replacement
therapy (RRT) may influence patients' quality of life and prognosis. Northern
Norway constitutes 45% of Norway's landmass, but has less than 10% of the
population. Methods In this study, we analysed all patients in northern Norway
consecutively registered in the Norwegian Renal Registry during 2000-2012. A
total of 634 patients (Nordland County 321 patients, Troms County 215 patients
and Finnmark County 98 patients) were investigated. Results There were more
smokers (31% vs. 22%) and patients with diabetes (32% vs. 22%) in Finnmark, but
the difference did not reach statistical significance. Patients undergoing RRT
and living in Finnmark County had a significantly worse outcome (P=0.03). The
median survivals after initiation of RRT were 3.8 years (Finnmark), 6.4 years
(Troms) and 5.4 years (Nordland), respectively. The most common causes of death
were cardiovascular disease (53%), infections (16%), withdrawal from therapy
(15%) and malignancy (13%). In a Cox analysis, age (P<0.0001), diabetes (P=0.008)
and smoking at any time (P<0.004) were individual factors correlated with
inferior prognosis. Conclusion Age, smoking and diabetes were prognostic factors.
Residents of the northernmost county (Finnmark) experienced an inferior
prognosis. Long distance from residence location to hospital may be another
factor, but this could not be documented. Preventive strategies should be
improved.
PMID- 28417824
TI - Adequate vitamin D levels in a Swedish population living above latitude 63
degrees N: The 2009 Northern Sweden MONICA study.
AB - Background Even though vitamin D is mainly produced by exposure to sunlight,
little is known regarding vitamin D levels in populations living in sub-Arctic
areas with little or no daylight during winter. Objective We describe
distributions of vitamin D3 and the prevalence of adequate levels in a population
living above 63 degrees N. Design We sampled 1,622 randomly selected subjects,
aged 25-74 years, between January and May, 2009, as part of the Northern Sweden
MONICA study (69.2% participation rate). By using HPLC, 25(OH) vitamin D3 was
analysed. Levels used for definitions were deficient, D3<25 nmol/l (<10 ng/ml);
insufficient, D3 25-49.9 nmol/l (10-20 ng/ml); and adequate, D3>=50 nmol/l (20
ng/ml). Results Mean (median) level of vitamin D3 was 65.2 (63.6) nmol/l in men
and 71.0 (67.7) nmol/l in women. Adequate levels were found in 79.2%, more often
in women (82.7%) than in men (75.6%). Only 0.7% of the population were vitamin D3
deficient but 23.1% of men and 17.1% of women had insufficient levels. Levels of
vitamin D3 increased with age and insufficient status was most common among those
aged 25-34 years, 41.0% in men and 22.3% in women. If subjects using vitamin D
supplementation are excluded, the population level of D3 is 1-2 nmol/l lower than
in the general population across sex- and age groups. There were no differences
between the northern or the southern parts, between urban or rural living or
according to educational attainment. Those subjects born outside of Sweden or
Finland had lower levels. Conclusion The large majority living close to the
Arctic Circle in Sweden have adequate D3 levels even during the second half of
the dark winter. Subjects with D3 deficiency were uncommon but insufficient
levels were often found among young men.
PMID- 28417825
TI - Incidence of syphilis in Greenland 2010-2014: The beginning of a new epidemic?
AB - Objective To estimate the incidence of syphilis from 2010 to 2014 and to assess
whether contact tracing has been performed. Study design Observational cross
sectional study. Method Data on reported cases were collected from the national
register of the chief medical officer in Greenland. Unreported cases were found
by searching the electronic medical record system for patients who had received
an electronic prescription of benzathine penicillin, doxycycline or tetracycline.
Medical records were reviewed to verify the diagnosis of syphilis and to evaluate
if contact tracing had been performed. Results Ninety-four cases of syphilis (51
males and 43 females) with a median age of 27 years (20-40) were included. The
incidence of syphilis in Greenland has increased from zero cases in 2010 to 95.7
per 100,000 inhabitants in 2014 affecting mainly young people. Contact tracing
was performed in 80.9% (76/94) of the cases. Conclusion Syphilis has re-occurred
in Greenland and a new epidemic may be underway. Sustained awareness of
treatment, contact tracing, monitoring and preventive initiatives are desirable.
PMID- 28417826
TI - Temporal trends of alcohol and drug use among Inuit of Northern Quebec, Canada.
AB - Background Alcohol and drug use is a serious health problem for many indigenous
populations across Canada, including Inuit. The literature on substance use in
these populations is too sparse to devise public health interventions. Objective
The present article portrays alcohol and drug use among Inuit living in Nunavik
(Northern Quebec) between the 1990s and 2000s, and identifies socio-demographic
characteristics related to substance use. Design The Sante Quebec Health Survey
(1992) and the Nunavik Inuit Health Survey Qanuippitaa (2004) served as databases
for this empirical work. Statistical comparisons were made of substance use
variables in the 2 samples. Proportions were compared by chi-square tests
(p<=0.05) with benchmarking of statistics for all of Quebec and, when available,
all of Canada. Results Alcohol and drug use among Inuit increased significantly
between 1992 and 2004, particularly among young adults. Alcohol users consumed
significantly more alcohol per drinking episode than other Canadians in both time
periods. Considerable cannabis use was widespread. In 2004, no significant
differences in frequencies of heavy drinking episodes were observed by gender,
with 60% of drug users consuming alcohol on a regular basis. Conclusions As in
other populations from North America, this study profiles the increase in
substance use among Inuit from Nunavik in the first part of the last 20 years. We
observed distinct substance use patterns among them in comparison to other
Canadians. Such findings, if replicated in the coming years, emphasize the need
for major, culturally-relevant public health interventions in this population.
PMID- 28417827
TI - Fatty acids linked to cardiovascular mortality are associated with risk factors.
AB - Background Although saturated fatty acids (FAs) have been linked to
cardiovascular mortality, it is not clear whether this outcome is attributable
solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether
other risk factors are also associated with FAs. The Western Alaskan Native
population, with its rapidly changing lifestyles, shift in diet from unsaturated
to saturated fatty acids and dramatic increase in cardiovascular disease (CVD),
presents an opportunity to elucidate any associations between specific FAs and
known CVD risk factors. Objective We tested the hypothesis that the specific FAs
previously identified as related to CVD mortality are also associated with
individual CVD risk factors. Methods In this community-based, cross-sectional
study, relative proportions of FAs in plasma and red blood cell membranes were
compared with CVD risk factors in a sample of 758 men and women aged >=35 years.
Linear regression analyses were used to analyze relations between specific FAs
and CVD risk factors (LDL-C, high-density lipoprotein cholesterol, triglycerides,
C-reactive protein, systolic blood pressure, diastolic blood pressure, heart
rate, body mass index, fasting glucose and fasting insulin, 2-hour glucose and 2
hour insulin). Results The specific saturated FAs previously identified as
related to CVD mortality, the palmitic and myristic acids, were adversely
associated with most CVD risk factors, whereas unsaturated linoleic acid (18:2n
6) and the marine n-3 FAs were not associated or were beneficially associated
with CVD risk factors. Conclusions The results suggest that CVD risk factors are
more extensively affected by individual FAs than hitherto recognized, and that
risk for CVD, MI and stroke can be reduced by reducing the intake of palmitate,
myristic acid and simple carbohydrates and improved by greater intake of linoleic
acid and marine n-3 FAs.
PMID- 28417828
TI - Seasonal prevalence and determinants of food insecurity in Iqaluit, Nunavut.
AB - Background Food insecurity is an ongoing problem in the Canadian Arctic. Although
most studies have focused on smaller communities, little is known about food
insecurity in larger centres. Objectives This study aimed to estimate the
prevalence of food insecurity during 2 different seasons in Iqaluit, the
territorial capital of Nunavut, as well as identify associated risk factors.
Designs A modified United States Department of Agriculture Food Security Survey
was applied to 532 randomly selected households in September 2012 and 523 in May
2013. Chi-square tests and multivariable logistic regression were used to examine
potential associations between food security and 9 risk factors identified in the
literature. Results In September 2012, 28.7% of surveyed households in Iqaluit
were food insecure, a rate 3 times higher than the national average, but lower
than smaller Inuit communities in Nunavut. Prevalence of food insecurity in
September 2012 was not significantly different in May 2013 (27.2%). When
aggregating results from Inuit households from both seasons (May and September),
food insecurity was associated with poor quality housing and reliance on income
support (p<0.01). Unemployment and younger age of the person in charge of food
preparation were also significantly associated with food insecurity. In contrast
to previous research among Arctic communities, gender and consumption of country
food were not positively associated with food security. These results are
consistent with research describing high food insecurity across the Canadian
Arctic. Conclusion The factors associated with food insecurity in Iqaluit
differed from those identified in smaller communities, suggesting that
experiences with, and processes of, food insecurity may differ between small
communities and larger commercial centres. These results suggest that country
food consumption, traditional knowledge and sharing networks may play a less
important role in larger Inuit communities.
PMID- 28417831
TI - Hand-Over Time.
PMID- 28417832
TI - Color Vision in Color Display Night Vision Goggles.
AB - INTRODUCTION: Aircrew viewing eyepiece-injected symbology on color display night
vision goggles (CDNVGs) are performing a visual task involving color under highly
unnatural viewing conditions. Their performance in discriminating different
colors and responding to color cues is unknown. METHODS: Experimental laboratory
measurements of 1) color discrimination and 2) visual search performance are
reported under adaptation conditions representative of a CDNVG. Color
discrimination was measured using a two-alternative forced choice (2AFC) paradigm
that probes color space uniformly around a white point. Search times in the
presence of different degrees of clutter (distractors in the scene) are measured
for different potential symbology colors. RESULTS: The discrimination data
support previous data suggesting that discrimination is best for colors close to
the adapting point in color space (P43 phosphor in this case). There were highly
significant effects of background adaptation (white or green) and test color. The
search time data show that saturated colors with the greatest chromatic contrast
with respect to the background lead to the shortest search times, associated with
the greatest saliency. Search times for the green background were around 150 ms
longer than for the white. Desaturated colors, along with those close to a
typical CDNVG display phosphor in color space, should be avoided by CDNVG
designers if the greatest conspicuity of symbology is desired. DISCUSSION: The
results can be used by CDNVG symbology designers to optimize aircrew performance
subject to wider constraints arising from the way color is used in the existing
conventional cockpit instruments and displays.Liggins EP, Serle WP. Color vision
in color display night vision goggles. Aerosp Med Hum Perform. 2017; 88(5):448
456.
PMID- 28417833
TI - Jugular and Portal Vein Volume, Middle Cerebral Vein Velocity, and Intracranial
Pressure in Dry Immersion.
AB - BACKGROUND: The objective was to determine if short term exposure to dry
immersion (DI) results in a cephalic fluid shift similar to what has been
observed with spaceflight. METHODS: Data were collected from 10 individuals at
rest and during the first 2 h of dry immersion. Jugular vein (JV), portal vein
(PV), and thyroid volume were measured using 3D echography. Middle cerebral vein
velocity (MCVv) was determined using transcranial Doppler ultrasound. The
cochlear response to audio stimulation was used to derive an estimate of
intracranial pressure (dICP). RESULTS: After 2 h of DI, there was a significant
increase (mean +/- SD) in JV (2.21 +/- 1.10 mL), PV (1.05 +/- 0.48 mL), and
thyroid (0.428 +/- 0.313 mL) volume. MCVv was also significantly increased with
DI (3.90 +/- 5.03 cm . s-1). There was no change in dICP with DI in part due to
large individual variability. The range of dICP changes appeared to be related to
MCVv, with participants with the largest increase in MCVv also showing increased
dICP. DISCUSSION: The results suggest that DI induces a significant cephalic
fluid shift similar to what is observed with spaceflight. The increased thyroid
volume suggests that cerebral tissue may also be subjected to similar fluid
filtration, with implications for changes in intracranial pressure. However,
despite all participants having an increase in JV and thyroid volume, only half
showed an increase in dICP, suggesting that increased venous pooling alone is not
sufficient to cause increased intracranial pressure.Arbeille P, Avan P, Treffel
L, Zuj K, Normand H, Denise P. Jugular and portal vein volume, middle cerebral
vein velocity, and intracranial pressure in dry immersion. Aerosp Med Hum
Perform. 2017; 88(5):457-462.
PMID- 28417834
TI - Adaptive Changes in the Perception of Fast and Slow Movement at Different Head
Positions.
AB - BACKGROUND: This paper examines the subjective sense of orientation during
asymmetric body rotations in normal subjects. METHODS: Self-motion perception was
investigated in 10 healthy individuals during asymmetric whole-body rotation with
different head orientations. Both on-vertical axis and off-vertical axis
rotations were employed. Subjects tracked a remembered earth-fixed visual target
while rotating in the dark for four cycles of asymmetric rotation (two half
sinusoidal cycles of the same amplitude, but of different duration). RESULTS: The
rotations induced a bias in the perception of velocity (more pronounced with fast
than with slow motion). At the end of rotation, a marked target position error
(TPE) was present. For the on-vertical axis rotations, the TPE was no different
if the rotations were performed with a 30 degrees nose-down, a 60 degrees nose
up, or a 90 degrees side-down head tilt. With off-vertical axis rotations, the
simultaneous activation of the semicircular canals and otolithic receptors
produced a significant increase of TPE for all head positions. DISCUSSIONS: This
difference between on-vertical and off-vertical axis rotation was probably partly
due to the vestibular transfer function and partly due to different adaptation to
the speed of rotation. Such a phenomenon might be generated in different
components of the vestibular system. The adaptive process enhancing the
perception of dynamic movement around the vertical axis is not related to the
specific semicircular canals that are activated; the addition of an otolithic
component results in a significant increase of the TPE.Panichi R, Occhigrossi C,
Ferraresi A, Faralli M, Lucertini M, Pettorossi VE. Adaptive changes in the
perception of fast and slow movement at different head positions. Aerosp Med Hum
Perform. 2017; 88(5):463-468.
PMID- 28417835
TI - Objective vs. Subjective Evaluation of Cognitive Performance During 0.4-MPa Dives
Breathing Air or Nitrox.
AB - BACKGROUND: Divers try to limit risks associated with their sport, for instance
by breathing enriched air nitrox (EANx) instead of air. This double blinded,
randomized trial was designed to see if the use of EANx could effectively improve
cognitive performance while diving. METHODS: Eight volunteers performed two no
decompression dry dives breathing air or EANx for 20 min at 0.4 MPa. Cognitive
functions were assessed with a computerized test battery, including MathProc and
Ptrail. Measurements were taken before the dive, upon arrival and after 15 min at
depth, upon surfacing, and at 30 min postdive. After each dive subjects were
asked to identify the gas they had just breathed. RESULTS: Identification of the
breathing gas was not possible on subjective assessment alone, while cognitive
assessments showed significantly better performance while breathing EANx. Before
the dives, breathing air, mean time to complete the task was 1795 ms for MathProc
and 1905 ms for Ptrail. When arriving at depth MathProc took 1616 ms on air and
1523 ms on EANx, and Ptrail took 1318 ms on air and and 1356 ms on EANx, followed
15 min later by significant performance inhibition while breathing air during the
ascent and the postdive phase, supporting the concept of late dive/postdive
impairment. DISCUSSION: The results suggest that EANx could protect against
decreased neuro-cognitive performance induced by inert gas narcosis. It was not
possible for blinded divers to identify which gas they were breathing and
differences in postdive fatigue between air and EANx diving deserve further
investigation.Germonpre P, Balestra C, Hemelryck W, Buzzacott P, Lafere P.
Objective vs. subjective evaluation of cognitive performance during 0.4-MPa dives
breathing air or nitrox. Aerosp Med Hum Perform. 2017; 88(5):469-475.
PMID- 28417836
TI - Cervical Spine Status of Pilots and Air-Controllers of Airborne Early Warning and
Control Aircraft.
AB - INTRODUCTION: Many countries have developed their own airborne early warning and
control (AEW&C) systems for use in surveying their territorial sky in real time.
However, a review of the literature suggests that no studies have been conducted
to analyze the cervical spine of pilots and air-controllers of AEW&C aircraft.
METHODS: The study subjects were 80 pilots and air-controllers of AEW&C aircraft
with a period of service of > 1 yr and had data on physical examinations, simple
radiographs and functional scores of the axial skeleton, and questionnaires about
lifestyle and working conditions. Information about physical characteristics and
experience of neck pain were collected. Functional scores including the neck
disability index and short-form 36-item health survey were obtained. Radiological
measurements were performed for the C2-7 Cobb angle and degree of forward head
posture. RESULTS: Of the 80 subjects, 33 (41.3%) had experienced neck pain and 63
(78.8%) had impaired cervical lordosis. The results of functional and
radiological evaluations were not significantly different between pilots and air
controllers. In multivariate analysis, only the age was significantly related to
the occurrence of impaired cervical lordosis. However, there were no significant
factors related to the occurrence of neck pain. DISCUSSION: The results of this
study suggest that the working environment of pilots and air-controllers of AEW&C
aircraft has a negative effect on their cervical spine. Age seemed to be the most
significant factor affecting the occurrence of impaired cervical lordosis in
these subjects.Shin YH, Yun C, Han AH. Cervical spine status of pilots and air
controllers of airborne early warning and control aircraft. Aerosp Med Hum
Perform. 2017; 88(5):476-480.
PMID- 28417837
TI - Flight Crew Workload Evaluation Based on the Workload Function Distribution
Method.
AB - BACKGROUND: The minimum flight crew on the flight deck should be established
according to the workload for individual crewmembers. Typical workload measures
consist of three types: subjective rating scale, task performance, and
psychophysiological measures. However, all these measures have their own
limitations. To reflect flight crew workload more specifically and
comprehensively within the flight environment, and more directly comply with
airworthiness regulations, the Workload Function Distribution Method, which
combined the basic six workload functions, was proposed. METHODS: The analysis
was based on the different conditions of workload function numbers. Each
condition was analyzed from two aspects, which were overall proportion and
effective proportion. Three types of approach tasks were used in this study and
the NASA-TLX scale was implemented for comparison. RESULTS: Neither the one
function condition nor the two-function condition had the same results with NASA
TLX. However, both the three-function and the four- to six- function conditions
were identical with NASA-TLX. Further, the significant differences were different
on four to six conditions. The overall proportion was insignificant, while the
effective proportions were significant. DISCUSSION: The results show that the
conditions with one function and two functions seemed to have no influence on
workload, while executing three functions and four to six functions had an impact
on workload. Besides, effective proportions of workload functions were more
precisely compared with the overall proportions to indicate workload, especially
in the conditions with multiple functions.Zheng Y, Lu Y, Jie Y, Fu S. Flight crew
workload evaluation based on the workload function distribution method. Aerosp
Med Hum Perform. 2017; 88(5):481-486.
PMID- 28417838
TI - Transferring Aviation Practices into Clinical Medicine for the Promotion of High
Reliability.
AB - BACKGROUND: Aviation is a classic example of a high reliability organization
(HRO)-an organization in which catastrophic events are expected to occur without
control measures. As health care systems transition toward high reliability,
aviation practices are increasingly transferred for clinical implementation.
METHODS: A PubMed search using the terms aviation, crew resource management, and
patient safety was undertaken. Manuscripts authored by physician pilots and
accident investigation regulations were analyzed. Subject matter experts involved
in adoption of aviation practices into the medical field were interviewed.
RESULTS: A PubMed search yielded 621 results with 22 relevant for inclusion.
Improved clinical outcomes were noted in five research trials in which aviation
practices were adopted, particularly with regard to checklist usage and crew
resource-management training. Effectiveness of interventions was influenced by
intensity of application, leadership involvement, and provision of staff
training. The usefulness of incorporating mishap investigation techniques has not
been established. Whereas aviation accident investigation is highly standardized,
the investigation of medical error is characterized by variation. DISCUSSION: The
adoption of aviation practices into clinical medicine facilitates an evolution
toward high reliability. Evidence for the efficacy of the checklist and crew
resource-management training is robust. Transference of aviation accident
investigation practices is preliminary. A standardized, independent investigation
process could facilitate the development of a safety culture commensurate with
that achieved in the aviation industry.Powell-Dunford N, McPherson MK, Pina JS,
Gaydos SJ. Transferring aviation practices into clinical medicine for the
promotion of high reliability. Aerosp Med Hum Perform. 2017; 88(5):487-491.
PMID- 28417839
TI - Mortality Due to Cardiovascular Disease Among Apollo Lunar Astronauts.
AB - INTRODUCTION: Recent research has postulated increased cardiovascular mortality
for astronauts who participated in the Apollo lunar missions. The conclusions,
however, are based on small numbers of astronauts, are derived from methods with
known weaknesses, and are not consistent with prior research. METHODS: Records
for NASA astronauts and U.S. Air Force astronauts were analyzed to produce
standardized mortality ratios. Lunar astronauts were compared to astronauts who
have never flown in space (nonflight astronauts), those who have only flown
missions in low Earth orbit (LEO astronauts), and the U.S. general population.
RESULTS: Lunar astronauts were significantly older at cohort entry than other
astronaut group and lunar astronauts alive as of the end of 2015 were
significantly older than nonflight astronauts and LEO astronauts. No significant
differences in cardiovascular disease (CVD) mortality rates between astronaut
groups was observed, though lunar astronauts were noted to be at significantly
lower risk of death by CVD than are members of the U.S. general population (SMR =
13, 95% CI = 3-39). DISCUSSION: The differences in age structure between lunar
and nonlunar astronauts and the deaths of LEO astronauts from external causes at
young ages lead to confounding in proportional mortality studies of astronauts.
When age and follow-up time are properly taken into account using cohort-based
methods, no significant difference in CVD mortality rates is observed. Care
should be taken to select the correct study design, outcome definition, exposure
classification, and analysis when answering questions involving rare occupational
exposures.Reynolds RJ, Day SM. Mortality due to cardiovascular disease among
Apollo lunar astronauts. Aerosp Med Hum Perform. 2017; 88(5):492-496.
PMID- 28417840
TI - Emergency Highway Landings in General Aviation and the Possible Role of Media
Reports.
AB - BACKGROUND: To examine the causes and factors of airplane landings on highways
and the dangers to occupants of vehicles on the ground. METHODS: The U.S.
National Transportation Safety Board online database provided 133 accidents
involving a highway landing dating from 2000 to 2013. Supplemental information
was sought in online media archives, which reported on 53 of these accidents.
Collisions with highway-related objects, other options for landing, and witness
accounts were added categories extracted from the narrative statements and media
reports. RESULTS: Highway landings occur mostly due to mechanical failures,
ineffective preflight or in-flight planning, and fuel exhaustion, in addition to
a lack of alternate landing options for a pilot of a fixed-wing aircraft. Most of
the landings (N = 108) lead to minor or no injuries at all. A significant
proportion of 7 out of 19 collisions with powerlines resulted in a fatality, as
opposed to other types of accidents. Collisions with motor vehicles (N = 29)
caused minor (N = 23) and serious (N = 2) injuries to people on the ground. Main
online media archives covered less than half of all accidents (39.8%).
DISCUSSION: While highway landings are not a recommended landing alternative,
mitigation strategies should include a focus on avoiding powerlines and vehicles
on the ground. Unfortunately, online media archives are not yet a consistent
source of information for general aviation accidents.Holzman E, de Voogt A.
Emergency highway landings in general aviation and the possible role of media
reports. Aerosp Med Hum Perform. 2017; 88(5):497-499.
PMID- 28417841
TI - Benign Episodic Unilateral Mydriasis in a Flight Nurse.
AB - BACKGROUND: Benign episodic unilateral mydriasis is one cause of anisocoria. This
phenomenon is thought to be related to an imbalance between the sympathetic and
parasympathetic nervous systems. There is a documented association with
migraines, but asymptomatic cases have also been reported. A challenge with all
cases is the level of investigation required to exclude more sinister causes of
nervous system dysfunction. In a dynamic flight environment, additional
considerations need to be made, such as varying light levels and use of night
vision devices. CASE REPORT: A 27-yr-old woman on deployment to Afghanistan as a
flight nurse presented to the role one clinic with right-sided mydriasis. The
patient denied headache or any history of migraines. A dilated right pupil that
was reactive to light was found on exam. Symptoms and exam findings resolved
shortly after initial presentation. We consulted an ophthalmologist who requested
patient transfer for review. He made a diagnosis of benign episodic unilateral
mydriasis. DISCUSSION: There are a variety of causes for anisocoria. A thorough
history and examination are required to avoid unnecessary investigations that may
not be locally available in the more austere deployed military settings. From an
operational perspective, the decision needs to be made regarding the maintenance
of flight status. Consideration needs to be given to patient care capability when
treating a flight nurse. In cases of rapid resolution such as this, removal from
operational status is not reasonable should a clinician be confident of the
diagnosis.Schiemer A. Benign episodic unilateral mydriasis in a flight nurse.
Aerosp Med Hum Perform. 2017; 88(5):500-502.
PMID- 28417842
TI - Blood-Injection-Injury (B-I-I) Specific Phobia Affects the Outcome of Hypoxic
Challenge Testing.
AB - BACKGROUND: Blood-injection-injury (B-I-I) phobia is capable of producing
inaccurate hypoxic challenge testing results due to anxiety-induced
hyperventilation. CASE REPORT: A 69-yr-old woman with a history of
hypersensitivity pneumonitis, restrictive spirometry, exercise desaturation
requiring supplementary oxygen on mobilizing, reduced DLco, and B-I-I phobia was
referred for hypoxic challenge testing (HCT) to assess in-flight oxygen
requirements. HCT was performed by breathing a 15% FIo2 gas mixture, simulating
the available oxygen in ambient air onboard aircraft pressurized to an equivalent
altitude of 8000 ft. Spo2 fell to a nadir value of 81% during HCT, although it
rapidly increased to 89% during the first of two attempts at blood gas sampling.
A resultant blood gas sample showed an acceptable Po2 outside the criteria for
recommending in-flight oxygen and a reduced Pco2. Entering the nadir Spo2 value
into the Severinghaus equation gives an estimated arterial Po2 of 6 kPa (45
mmHg), which was felt to be more representative of resting values during HCT, and
in-flight oxygen was recommended. DISCUSSION: While hyperventilation is an
expected response to hypoxia, transient rises in Spo2 coinciding with threat of
injury are likely to be attributable to emotional stress-induced
hyperventilation, characteristic of B-I-I specific phobia and expected during the
anticipation of exteroceptive threat, even in normal subjects. In summary, should
excessive hyperventilation be detected during HCT and coincide with transient
increases in Spo2, HCT should be repeated using Spo2 only as a guide to the level
of hypoxemia, and Spo2 maintained using supplementary oxygen in accordance with
alternative methods described in guidelines.Spurling KJ, McGoldrick VP. Blood
injection-injury (B-I-I) specific phobia affects the outcome of hypoxic challenge
testing. Aerosp Med Hum Perform. 2017; 88(5):503-506.
PMID- 28417843
TI - Letter to the Editor re: Hypoxia Occurrence in a Military Aviator Below 3048 m:
Letter.
PMID- 28417844
TI - You're the Flight Surgeon.
AB - McLaughlin CM. You're the flight surgeon: atypical hypothyroid presentation.
Aerosp Med Hum Perform. 2017; 88(5):509-511.
PMID- 28417845
TI - You're the Flight Surgeon.
AB - Chumbley EM. You're the flight surgeon: a case of bilateral leg pain and swelling
in a loadmaster. Aerosp Med Hum Perform. 2017; 88(5):511-515.
PMID- 28417846
TI - Captain Nels O. Monserud and Medical Consideration of the Women Air Force Service
Pilots: An Enduring Legacy.
PMID- 28417847
TI - This Month in Aerospace Medicine History.
PMID- 28417849
TI - Letter From the Editors.
PMID- 28417848
TI - Dynamic range adaptation in primary motor cortical populations.
AB - Neural populations from various sensory regions demonstrate dynamic range
adaptation in response to changes in the statistical distribution of their input
stimuli. These adaptations help optimize the transmission of information about
sensory inputs. Here, we show a similar effect in the firing rates of primary
motor cortical cells. We trained monkeys to operate a brain-computer interface in
both two- and three-dimensional virtual environments. We found that neurons in
primary motor cortex exhibited a change in the amplitude of their directional
tuning curves between the two tasks. We then leveraged the simultaneous nature of
the recordings to test several hypotheses about the population-based mechanisms
driving these changes and found that the results are most consistent with dynamic
range adaptation. Our results demonstrate that dynamic range adaptation is
neither limited to sensory regions nor to rescaling of monotonic stimulus
intensity tuning curves, but may rather represent a canonical feature of neural
encoding.
PMID- 28417850
TI - Guest Editorial.
PMID- 28417851
TI - Nuclear Medicine Techniques in Pediatric Bone Imaging.
AB - An important mandate when imaging pediatric patients is the reduction of
radiation exposure to the lowest possible level consistent with good quality
diagnostic imaging, so individual selection of radiopharmaceutical dosage and
imaging technique is essential. Although the logistics of image acquisition and
the approach to interpretation mirror the more common use in adults, the
challenges of imaging young children typically require greater attention to
patient preparation, positioning, and supervision during imaging, with the use of
parental or family engagement in the procedure, gentle restraint, and
occasionally the need for sedation. Because the normal bone scan appearance
varies dramatically with age as osseous structures mature, it is critical that
the interpreting physician be well versed in the range of normal variability at
each developmental stage. Although routinely employed in the evaluation of
malignancy, radionuclide bone imaging in children is used for a much wider range
of benign disorders than it is typical in adults. In many pediatric nuclear
medicine departments, the evaluation of benign bone disorders represents most
imaging procedures. Common indications include the evaluation of sports injuries,
osteomyelitis, trauma, including suspected child abuse, growth disorders, such as
mandibular condyle asymmetry, and noninfectious processes such as Langerhans cell
histiocytosis. Both planar scintigraphy and SPECT imaging are widely employed,
although the SPECT acquisition time presents a barrier in some age groups, making
shorter planar spot views desirable when feasible. PET bone imaging with 18F
sodium fluoride has been shown useful in a number of pediatric disorders, but may
present issues in young children, as it can require the use of sedation. Despite
this challenge, the higher resolution and resulting better anatomical depiction
of bone anatomy by PET techniques can be very valuable in evaluating small
structures, and current experience suggests a large future role for fluoride PET
imaging.
PMID- 28417852
TI - Nuclear Medicine in Pediatric Nephro-Urology: An Overview.
AB - In the context of ante-natally diagnosed hydronephrosis, the vast majority of
children with a dilated renal pelvis do not need any surgical treatment, as the
dilatation resolves spontaneously with time. Slow drainage demonstrated at Tc-99m
mercaptoacetyltriglycine (MAG3) renography does not necessarily mean obstruction.
Obstruction is defined as resistance to urinary outflow with urinary stasis at
the level of the pelvic-ureteric junction (PUJ) which, if left untreated, will
damage the kidney. Unfortunately this definition is retrospective and not
clinically helpful. Therefore, the identification of the kidney at risk of losing
function in an asymptomatic patient is a major research goal. In the context of
renovascular hypertension a DMSA scan can be useful before and after
revascularisation procedures (angioplasty or surgery) to assess for gain in
kidney function. Renal calculi are increasingly frequent in children. Whilst the
vast majority of patients with renal stones do not need functional imaging, DMSA
scans with SPECT and a low dose limited CT can be very helpful in the case of
complex renal calculi. Congenital renal anomalies such as duplex kidneys,
horseshoe kidneys, crossed-fused kidneys and multi-cystic dysplastic kidneys
greatly benefit from functional imaging to identify regional parenchymal
function, thus directing further management. Positron emission tomography (PET)
is being actively tested in genito-urinary malignancies. Encouraging initial
reports suggest that F-18-fluorodeoxyglucose (FDG) PET is more sensitive than CT
in the assessment of lymph nodal metastases in patients with genito-urinary
sarcomas; an increased sensitivity in comparison to isotope bone scans for
skeletal metastatic disease has also been reported. Further evaluation is
necessary, especially with the promising advent of PET/MRI scanners. Nuclear
Medicine in paediatric nephro-urology has stood the test of time and is opening
up to new exciting developments.
PMID- 28417853
TI - The Role of 18F-FDG-PET/CT in Pediatric Sarcoma.
AB - Considerable debate remains regarding how best to incorporate 18F-FDG-PET/CT into
clinical practice for pediatric sarcomas. Although there is a clear role for 18F
FDG-PET/CT in staging pediatric sarcoma, the value of 18F-FDG-PET/CT in
prognostication for pediatric sarcomas remains unclear. In osteosarcoma, Ewing
sarcoma, and rhabdomyosarcoma, 18F-FDG-PET/CT may be most useful in the
identification of skeletal metastases, where the literature consistently suggests
that it has improved sensitivity and specificity as compared to bone
scintigraphy. The role of the imaging modality in the identification of pulmonary
metastatic disease is less clear. Further controversy exists regarding the use of
18F-FDG-PET/CT in predicting outcome. Several studies, particularly in
osteosarcoma, suggest changes in the maximal standardized uptake value (SUVmax)
that can predict histologic response following neoadjuvant chemotherapy as well
as overall outcome. Conversely, studies are conflicting regarding the use of 18F
FDG-PET/CT as a prognostic tool in Ewing sarcoma and rhabdomyosarcoma. The role
of 18F-FDG-PET/CT in pediatric nonrhabdomyosarcoma soft tissue sarcomas is
unknown at this time. Although most studies have been small and retrospective, in
certain histologic subtypes, there is a clear role for the use of this imaging
modality. Additional prospective and larger studies are needed to fully determine
how best to incorporate 18F-FDG-PET/CT into treatment regimens for pediatric
sarcomas in the future.
PMID- 28417854
TI - Current Role of FDG-PET in Pediatric Hodgkin's Lymphoma.
AB - Hodgkin's lymphoma is one of the most curable pediatric cancers with long-term
survival rates exceeding 90% following intensive treatment. Collaborative group
studies worldwide aim on reduction or elimination of radiotherapy to avoid
potentially life-limiting late effects especially second cancers and
cardiovascular diseases. Large prospective trials have integrated early response
FDG-PET scans to identify adequate responders to chemotherapy in whom
radiotherapy may safely be omitted. The criteria for interpretation of early
response PET have changed during the past years and will be further refined based
on trial results. FDG-PET is also systematically used to assess initial disease
involvement of pediatric Hodgkin's lymphoma and could replace bone marrow biopsy.
This article summarizes the role of FDG-PET in staging and response assessment
focusing on large pediatric trials, the criteria for PET interpretation and
pitfalls.
PMID- 28417855
TI - Optimization of Pediatric PET/CT.
AB - PET/CT, the most common form of hybrid imaging, has transformed oncologic imaging
and is increasingly being used for nononcologic applications as well. Performing
PET/CT in children poses unique challenges. Not only are children more sensitive
to the effects of radiation than adults but, following radiation exposure,
children have a longer postexposure life expectancy in which to exhibit adverse
radiation effects. Both the PET and CT components of the study contribute to the
total patient radiation dose, which is one of the most important risks of the
study in this population. Another risk in children, not typically encountered in
adults, is potential neurotoxicity related to the frequent need for general
anesthesia in this patient population. Optimizing pediatric PET/CT requires
making improvements to both the PET and the CT components of the procedure while
decreasing the potential for risk. This can be accomplished through judicious
performance of imaging, the use of recommended pediatric 18fluorine-2-fluoro-2
deoxy-d-glucose (18F-FDG) administered activities, thoughtful selection of
pediatric-specific CT imaging parameters, careful patient preparation, and use of
appropriate patient immobilization. In this article, we will review a variety of
strategies for radiation dose optimization in pediatric 18F-FDG-PET/CT focusing
on these processes. Awareness of and careful selection of pediatric-specific CT
imaging parameters designed for appropriate diagnostic, localization, or
attenuation correction only CT, in conjunction with the use of recommended
radiotracer administered activities, will help to ensure image quality while
limiting patient radiation exposure. Patient preparation, an important
determinant of image quality, is another focus of this review. Appropriate
preparative measures are even more crucial in children in whom there is a higher
incidence of brown fat, which can interfere with study interpretation. Finally,
we will discuss measures to improve the patient experience, the resource use, the
departmental workflow, and the diagnostic performance of the study through the
use of appropriate technology, all in the context of minimizing procedure-related
risks.
PMID- 28417856
TI - Scintigraphic Evaluation of Gastroesophageal Reflux and Pulmonary Aspiration in
Children.
AB - Gastroesophageal reflux (GER) and pulmonary aspiration are encountered in
children of all ages. Signs, symptoms, and complications vary from mild and
transient to severe life-threatening conditions. This review will present
relevant clinical information on these conditions as well as common diagnostic
procedures. The role of scintigraphic techniques used in the evaluation of these
conditions will be discussed in detail including protocols and performance in
comparison to other diagnostic methods.
PMID- 28417857
TI - Nuclear Medicine Imaging in Pediatric Infection or Chronic Inflammatory Diseases.
AB - In this review article, we focus on the most recent applications of nuclear
medicine techniques (mainly 99mTc/111In white blood cells (WBC) scan, [18F]-FDG
PET/CT, [18F]-FDG-PET/MRI, and 99mTc-IL-2 scintigraphy) in the study of children
affected by peripheral bone osteomyelitis, fungal infections, inflammatory bowel
diseases, and type 1 diabetes, owing to recent important published evidences of
their role in the management of these diseases. For osteomyelitis in children,
both bone scintigraphy and [18F]-FDG-PET have a major advantage of assessing the
whole body in one imaging session to confirm or exclude multifocal involvement,
whereas WBC scan has a limited role. In children with fungal infections, [18F]
FDG-PET can help in defining the best location for biopsy and can help in
evaluating the extent of the infection and organs involved (also sites that were
not yet clinically apparent), although its main role is for therapy monitoring.
In inflammatory bowel diseases, and Crohn disease in particular, WBC scan has
been successfully used for many years, but it is now used only in case of
doubtful magnetic resonance (MR) or when MR cannot be performed and endoscopy is
inconclusive. By contrast, there is an accumulating evidence of the role of [18F]
FDG-PET in management of children with Crohn disease, and PET/MR could be a
versatile and innovative hybrid imaging technique that combines the metabolic
information of PET with the high soft tissue resolution of MR, particularly for
distinguishing fibrotic from active strictures. Finally, there are several new
radiopharmaceuticals that specifically target inflammatory cells involved in the
pathogenesis of insulitis aiming at developing new specific immunotherapies and
to select children candidates to these treatments for improving their quality of
life.
PMID- 28417858
TI - 18F-FDG-PET/CT Imaging of Thoracic and Extrathoracic Tuberculosis in Children.
AB - Tuberculosis (TB) remains a major health problem, affecting approximately one
third of the world's population. The tubercle bacillus can affect virtually any
organ of the human body and if left untreated can lead to severe morbidity and
death. Diagnosis of active TB is challenging, especially in children. As a "great
imitator," the disease can mimic numerous other pathologies, both clinically and
at imaging. Although recognition of active TB is crucial to initiate adequate
treatment in a timely fashion, thereby preventing transmission of disease,
differentiation of active and quiescent disease is not always straightforward.
Since the first reports more than 20 years ago, FDG-PET/CT imaging has been shown
to detect active disease with accuracy equal or superior to other conventional
imaging modalities. The role of FDG-PET in evaluating patients with TB is rapidly
expanding. FDG-PET/CT can effectively identify foci of intrathoracic and
extrathoracic TB, assess disease activity, differentiate between active and
latent disease, monitor response to therapy, identify potential biopsy targets,
and serve as a surrogate end point for new drug trials. Efficacy of FDG-PET/CT in
the especially challenging pediatric population will be the focus of this review.
PMID- 28417859
TI - Cardiovascular Surgery in the Elderly.
AB - The elderly population is the fastest growing demographic in Western countries.
As the population ages, the incidence of age-related comorbidities such as
diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular
disease, renal disease, cerebrovascular disease, and cardiovascular disease
increases. With cardiovascular disease occurring in approximately one-quarter of
the population over the age of 75 years and more than half of all cardiac
procedures performed on this age group, the number of potential elderly surgical
candidates is increasing. However, data suggest that old age is associated with
increased morbidity and mortality following cardiac surgery. Over the past 2
decades, improvements in myocardial protection, extracorporeal circulation,
anesthesia, and surgical techniques have significantly reduced the morbidity and
mortality associated with cardiac surgery. Although most prospective studies
exclude elderly patients, data from large retrospective studies and subgroup
analyses suggest that cardiac surgery is a viable option for many elderly
patients with cardiovascular disease, with good outcomes observed in reasonable
risk candidates; moreover, there are a growing number of available less-invasive
options for them when surgical risk becomes prohibitive. In this article, we
discuss the current state of cardiovascular surgery in the elderly as well as
emerging technologies on the horizon.
PMID- 28417860
TI - Similar Survival After Repair vs Replacement for Ischemic Mitral Regurgitation.
AB - To determine whether mitral valve (MV) repair improves early and late survival
compared with MV replacement for patients with ischemic mitral regurgitation
(IMR), we performed a meta-analysis of randomized controlled trials (RCTs) and
adjusted observational studies. Databases including MEDLINE, EMBASE, and the
Cochrane Central Register of Controlled Trials were searched through January 2016
using PubMed and Ovid. Studies considered for inclusion met the following
criteria: the design was a RCT or adjusted observational study, the study
population was patients with IMR; patients were assigned to MV repair vs
replacement, and outcomes included early (30 days or in hospital) or late (>=1
year) overall survival or all-cause mortality. An adjusted odds or hazard ratio
(OR/HR) with its 95% CI of early or late (including early) all-cause mortality
for MV repair vs replacement was abstracted from each individual study. Our
search identified 12 articles from one RCT and 10 adjusted observational studies
including 2784 patients. Pooled analyses demonstrated no significant difference
in both early (OR = 0.90; 95% CI: 0.69-1.16; P = 0.41) and late mortality (HR =
0.90; 95% CI: 0.72-1.13; P = 0.38) between MV repair and replacement. Exclusion
of any single study from the meta-analysis did not substantively alter the
overall result of no significant difference. There was no evidence of significant
publication bias. For patients with IMR, MV repair appears to be unassociated
with a significant decrease in both early and late all-cause mortality compared
with MV replacement.
PMID- 28417862
TI - Angel in the Architecture and the Devil in the Details: Comparative
Ultrastructure of Degenerative Mitral Valve Disease.
PMID- 28417861
TI - Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and
Fibroelastic Deficiency.
AB - Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of
mitral valve prolapse (MVP), should be considered 2 distinct diseases remains
unknown. Mitral valves from patients who required surgery for severe mitral
regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative
diagnosis of BD or FED was based on leaflet redundancy and thickness, number of
segments involved, and annular dimension. The removed medial scallop of the
posterior leaflet and attached chordae were used for histopathological and
immunohistological assessment. Histologically, compared to normal controls (n =
3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture
and increased thickness. Leaflet thickness was greater and chordae thickness
lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to
spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa
and atrialis; in FED, local thickening was predominant on the fibrosa side, with
accumulation of proteoglycan-like material around the chordae. Collagen
accumulation was observed in FED leaflets and chords and decreased in BD.
Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but
increased in FED leaflets and around chordae. Activated myofibroblasts accumulate
in both diseased leaflets and chords, but more abundantly in FED chordae (P <
0.0001), independently of age, suggesting a role of these cells in chordal
rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P
< 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were
more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P
< 0.01) indicating tissue remodeling. Upregulation of transforming growth factor
beta and pERK signaling pathways was evident in both diseases but more prominent
in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in
FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in
control valves. Quantitative immunohistopathological analyses demonstrated
distinct changes between BD and FED valves: predominant matrix degradation in BD
and increased profibrotic signaling pathways in FED, indicating that BD and FED
are 2 different entities. These results may pave the way for genetic studies of
MVP and development of preventive drug therapies.
PMID- 28417863
TI - Evaluation of a High-Fidelity Simulation Training Program for New Cardiothoracic
Intensive Care Unit Nurses.
AB - The objective of this article is to evaluate the effect of a high-fidelity
simulation training program on knowledge and confidence as part of a nursing
internship in the cardiothoracic intensive care unit. Ten nurse interns each
completed a simulation scenario involving common postoperative complications
followed by a group debriefing session. Knowledge and confidence were assessed
using a multiple-choice test and modified self-efficacy scale, respectively. Both
were administered precourse and postcourse and again 2 weeks later. The
simulation effectiveness tool, a 0-2 scale with higher scores indicating higher
degree of perceived effectiveness, was used to evaluate participants' perceptions
of the program. Paired t-tests compared precourse and postcourse scores as well
as postcourse and follow-up scores for both knowledge and confidence. Spearman
rho compared subjective with objective assessment of learning and improvement in
learning with improvement in confidence. Mean knowledge scores improved from
48.18% (standard deviation [SD] = 14.7) to 60.9% (SD = 22.6; P < 0.05) and
confidence scores improved from 20.8 (SD = 5.17) to 25.9 (SD = 3.3; P < 0.05),
both with insignificant changes 2 weeks later. The simulation effectiveness tool
mean score was 1.64 (SD = 0.56). There was no correlation between the objective
and subjective learning assessments or between the improvement in learning and
improvement in confidence. The inclusion of a high-fidelity simulation course
showed improvement in both learning and confidence among the new graduate nurses;
however, objective assessment of learning is needed. It is also important to note
that an improvement in confidence may not indicate an improvement in actual
ability.
PMID- 28417864
TI - Paradigm for Detecting Silent Thoracic Aneurysm Disease.
AB - Thoracic aortic aneurysms (TAA) pose a serious detection challenge owing to their
clinically silent nature. Only a small fraction of TAAs cause symptoms in
patients. However, the mortality burden of this disease in the population is
significant, given the high lethality of such complications as aortic rupture and
dissection. Widespread screening for TAA has not been shown to be cost-effective.
Therefore, currently most patients with a TAA are identified incidentally during
an imaging study conducted for other reasons. Once a TAA diagnosis is
established, prophylactic surgical treatment can safely be performed for
aneurysms of the ascending aorta, aortic arch, and descending or thoracoabdominal
aorta, thus preventing aneurysm-related death. To facilitate early detection of
TAA, recent studies have identified several "associates" of TAA that may be
useful in making a timely diagnosis. These "associates" include intracranial
aneurysm, aortic arch anomalies, abdominal aortic aneurysm, simple renal cysts,
bicuspid aortic valve, temporal arteritis, a positive family history of aneurysm
disease, and a positive thumb-palm sign, among others. Although for many of these
"associates" the underlying mechanism that would explain the association remains
to be elucidated, the clinical correlation is strong enough to suggest screening
patients with these findings for TAA. This article introduces the "Guilt by
Association" paradigm for detection of silent thoracic aortic disease based on
detection of clinical markers associated with this condition.
PMID- 28417865
TI - Management of Symptomatic Severe Aortic Stenosis in Patient With Very Severe
Chronic Obstructive Pulmonary Disease.
AB - Transcatheter aortic valve replacement (TAVR) is a viable option for patients
with severe chronic obstructive pulmonary disease (COPD) who are deemed
inoperable or high risk for surgery. We sought to determine outcomes of patients
with severe aortic stenosis (AS) and severe COPD referred for aortic valve
replacement (AVR). One hundred thirty-one patients with severe AS and severe COPD
(GOLD criteria) were evaluated at our center between 2008 and 2013 and were
divided retrospectively into 4 groups: 1-medical management, 2-balloon aortic
valvuloplasty, 3-surgical aortic valve replacement (SAVR), and 4-TAVR. Baseline,
clinical, and echo data were recorded. Primary outcome was cardiovascular death.
From the study cohort, 54 (41.2%), 29 (22.1%), 21 (16.0%), and 27 (20.6%) were
included in groups 1-4, respectively; the age was 74.9 +/- 8.8, 76.2 +/- 8.8,
78.8 +/- 7.4, and 82.8 +/- 6.8 years, respectively (P < 0.01). There was no
significant difference between the groups for hypertension, diabetes, aortic
valve area or gradients, forced expiratory volume in first second, right
ventricular systolic pressure, ejection fraction, and Society of Thoracic
Surgeons predicted risk of mortality score. At 3 +/- 1.5 years, death occurred in
87%, 97%, 47.7%, and 51.8% of patients in groups 1-4, respectively. Heart failure
readmissions occurred in 43%, 42%, 9.6%, and 14.8% of patients in groups 1-4,
respectively. When SAVR and TAVR groups were compared, there was no significant
difference in survival (P = 0.719) or heart failure readmissions (P = 0.19). In
patients with severe or very severe COPD and severe AS, replacing the severely
stenotic aortic valve by either SAVR or TAVR improves survival and reduces
rehospitalization compared with medical therapy or balloon aortic valvuloplasty.
PMID- 28417866
TI - Anomalous Aortic Origin of Coronary Arteries: A Single-Center Experience.
AB - The aim of this article is to determine the clinical course and outcomes in
subjects with anomalous aortic origin of coronary arteries (AAOCA), particularly
after surgical repair. A single-center, retrospective review of patients with
AAOCA with right or left interarterial or IM (IA or IM) or intraconal course from
1996-2014. Among 155 patients, median age at diagnosis was 8.5 (range: 0.1-50)
years, and 65% were male. The AAOCA course was IA or IM in 151 (97%) and
intraconal in 4 (3%). Anomalous right coronary artery (CA) was present in 127
(82%), of whom 52 (42%) had repair. Anomalous left CA (ALCA) was present in 28
(18%), of whom 20 (71%) had repair. In the surgical group, 70 (97%) had IA or IM
CAs; CA unroofing was performed in 62 (86%). In univariable analysis, surgical
management was associated with ALCA (28% vs 10%, P = 0.003), age > 10 years
(median 11 vs 6 years, P < 0.001), symptoms (63% vs 13%, P < 0.001), and exercise
restriction at the time of diagnosis (47% vs 13%, P < 0.001). In multivariable
modeling, surgery was associated with chest pain or syncope (P < 0.001) and older
age (P = 0.03). Major perioperative complications occurred in 4 cases (6%) and 1
patient had late aortic valve repair. In the surgical group, no patients died; in
the observed group, 2 patients with anomalous right CA (2.3%) died of severe
noncardiac comorbidities. In our center, surgery for AAOCA was not associated
with mortality, and surgery was recommended in patients with ALCA with IA or IM
course. Rare but serious surgical complications highlight the importance of long
term follow up of patients with AAOCA to develop evidence-based management
guidelines.
PMID- 28417867
TI - Wrong Sinus Coronary Arteries: Another Piece of the Puzzle.
PMID- 28417868
TI - Risk Factors for Unanticipated Readmissions During the Interstage: A Report From
the National Pediatric Cardiology Quality Improvement Collaborative.
AB - This study describes unanticipated interstage readmissions in patients with
hypoplastic left heart syndrome, identifies independent risk factors for
unanticipated interstage readmissions, and evaluates variation in unanticipated
readmission rates among collaborative centers. Retrospective data of patients
enrolled in the National Pediatric Cardiology Quality Improvement Collaborative
registry from July 2008 to July 2013 were analyzed. Risk factors present at the
beginning of the interstage were captured. Competing risks time to event analyses
determined the association between these factors and unanticipated interstage
readmission. Readmission center variation was examined using funnel plots.
Unanticipated interstage readmissions occurred in 66% of 815 patients at 50
centers. The median readmission length of stay was 2 days (interquartile range: 0
6) and median time to first readmission was 29 days (interquartile range: 9-63).
Most readmissions were prompted by minor changes in clinical status (64%),
whereas only 6% were major adverse event readmissions. Independent readmission
risk factors included genetic syndrome (HR = 1.40, 95% CI: 1.05-1.88), center
volume (small vs large HR = 1.32, CI: 1.04-1.66, medium vs large HR = 1.35, CI:
1.09-1.68), preoperative ventricular dysfunction (HR = 2.02, CI: 1.31-3.10),
tricuspid regurgitation (HR = 1.36, CI: 1.08-1.72), duration of circulatory
arrest (HR = 0.99, CI: 0.989-0.998), and undergoing Hybrid procedure relative to
Norwood/right ventricle to pulmonary artery conduit (HR = 1.40, CI: 1.02-1.93).
There was significant center variation in the number of readmissions and duration
of readmissions. Unanticipated readmissions are common during the interstage
period with notable center variation. However, these readmissions are short and
are rarely in response to major adverse events.
PMID- 28417869
TI - Unanticipated Readmissions During the Interstage Period in Patients With
Hypoplastic Left Heart Syndrome: Can the Numbers be Safely Reduced?
PMID- 28417870
TI - Intracoronary Stem Cell Delivery to the Right Ventricle: A Preclinical Study.
AB - Clinical protocols for stem cell-based therapies are currently under development
for patients with hypoplastic left heart syndrome. An ideal cell delivery method
should have minimal safety risks and provide a wide distribution of cells to the
nonischemic right ventricle (RV). However, the optimal strategy for stem cell
delivery to the RV has yet to be explored in a preclinical model, necessary for a
hypoplastic left heart syndrome trial. Human c-kit+ cardiac stem cells (CSCs)
were delivered to healthy Yorkshire swine through the proximal right coronary
artery with a stop and reflow technique. The effect of premedication with
antiarrhythmic (AA) medications in this model was retrospectively reviewed, with
the primary outcome of survival 2 hours after infusion. A group underwent CSC
delivery to the RV without prophylactic AA medication (no AA, n = 7), whereas the
second group was premedicated with a loading dose and intravenous infusion of
amiodarone and lidocaine (AA, n = 13). Cardiac biopsies were obtained from each
chamber to ascertain the biodistribution of CSCs. Survival was significantly
greater in the prophylactic AA group compared with the group without AA (13/13
[100%] vs 1/7 [14.3%], P < 0.0001). Cardiac arrest during balloon inflation was
the cause of death in each of the nonmedicated animals. In the premedicated
group, 9 (69.2%) pigs experienced transient ST segment changes in the precordial
leads during CSC delivery, which resolved spontaneously. Most c-kit+ CSCs were
distributed to lateral segments of the RV free wall, consistent with the
anatomical course of the right coronary artery (lateral RV, 19.2 +/- 1.5
CSCs/field of view vs medial RV, 10.4 +/- 1.3 CSCs/field of view, P < 0.0001).
Few c-kit+ CSCs were identified in the right atrium, septum, or left ventricle.
Prophylactic infusion of AA enhances survival in swine undergoing intracoronary
delivery of human c-kit+ CSCs to the RV. Additionally, intracoronary delivery
results in a limited biodistribution of c-kit+ CSCs within the RV. Human clinical
protocols can be optimized by requiring infusion of AA medications before cell
delivery.
PMID- 28417871
TI - A Light in the Darkness: Lighthouse or Anglerfish?
PMID- 28417872
TI - Brown adipose tissue and browning: More than just a heating device.
PMID- 28417873
TI - Trends in the incidence of lower limb amputation after implementation of a
Multidisciplinary Diabetic Foot Unit.
AB - BACKGROUNDS AND OBJECTIVE: Incidence of lower extremity amputations (LEA) in the
population with and without diabetes mellitus (DM) was assessed after
implementation of a Multidisciplinary Diabetic Foot Unit (MDFU) during 2008.
MATERIAL AND METHODS: Non-traumatic LEA were analyzed, and those performed before
(2001-2007) and after (2008-2014) introduction of the MDFU were compared. LEA
were grouped by age and sex. Their incidence was expressed as a rate per 100,000
population per year, adjusted to the standard European population. RESULTS: A
total of 664 LEA were performed during the 2001-2014 period, 486 (73%) of them in
patients with DM. Total LEA incidence was 11.2/105 population in DM versus
3.9/105 in the population without DM. Incidence of major LEA in patients with DM
significantly decreased from 6.1/105 population in the 2001-2007 period to
4.5/105 in the 2008-2014 period (p=.03). Joinpoint regression analysis also
showed a reduction in the trend of incidence of major LEA in patients with DM,
with an annual percentage change of -3.3% [95% CI, -6.2-0.3] (p=.025). No
significant differences were found for all other incidences and trends in the
diabetic and non-diabetic populations. CONCLUSIONS: Implementation of a MDFU has
been shown to be associated with a significant reduction in major amputation rate
in the diabetic population, although the results are not optimal yet. Both
results and work at the MDFU should be improved.
PMID- 28417874
TI - Effectiveness of MiniMed 640G with SmartGuard(r) System for prevention of
hypoglycemia in pediatric patients with type 1 diabetes mellitus.
AB - INTRODUCTION/AIMS: Treatment with the MiniMed 640G-SmartGuard(r) system (640G-SG,
sensor-augmented insulin pump system with low predicted glucose suspension
feature) has been shown to decrease risk of hypoglycemia without altering
metabolic control in patients with T1DM. The study purpose was to assess the
impact of 640G-SG on hipoglycemia frequency and on metabolic control in a
pediatric population with T1DM. PATIENTS/METHODS: A retrospective study on 21
children treated with 640G-SG. HbA1C, mean blood glucose (mg/dl), glucose
variation coefficient, frequency of hypoglycemia (<70mg/dl) and hyperglycemia
(>180mg/dl), daily capillary blood glucose measurements, ketosis/diabetic
ketoacidosis, and severe hypoglycemic episodes were analyzed and compared before
and during use of the system. Fasting blood glucose, frequency of sensor use and
number and duration of system suspension events were also assessed in the last
month of use of the system. RESULTS: All patients used the system continuously
(5.0+/-2.1 months), with a median sensor use of 92%. Significant decreases were
seen in hypoglycemia frequency (10.4+/-5.2% to 7.6+/-3.3%, p=.044) and number of
capillary blood glucose measurements (11.3+/-2,2 to 8.1+/-2,1, p<.001), and there
was no increase in hyperglycemia frequency (p=.65). Mean system suspension time
was 3.1+/-1.2hours/day (37.3% of overnight stops). Changes in HbA1c, mean blood
glucose, and variation coefficient were not significant. No patient experienced
diabetic ketoacidosis or severe hypoglycemia. CONCLUSIONS: The sensor-augmented
pump with the predictive low glucose suspension management system, as implemented
in the 640G-SG system, can help avoid risk of hypoglycemia without significantly
affecting metabolic control or causing diabetic ketoacidosis, and decrease the
burden of additional capillary blood glucose measurements in our pediatric
cohort.
PMID- 28417875
TI - Influence of malnutrition upon all-cause mortality among children in Swaziland.
AB - OBJECTIVE: To analyze the effect of the type of malnutrition, sex, age and the
presence of edema upon all-cause mortality in children under 5 years of age.
MATERIAL AND METHODS: A cross-sectional study was conducted during 2010 and 2011
in Swaziland. Sex, age, weight and height were taken to classify nutritional
status according to the 2006 WHO growth standards: stunting (low height for age),
wasting (low weight for height or low body mass index for age) and underweight
(low weight for age). The sample (309 boys and 244 girls under 5 years of age)
was analyzed by sex and age groups (under and equal/over 12 months). The
association between variables was evaluated using the chi2 test. Cox regression
analysis (HR, 95% CI) was used to assess the likelihood of mortality. RESULTS:
The mortality risk in malnourished children under one year of age was lower among
females and increased in the presence of severe edema. Wasting combined with
underweight increased the mortality risk in children under 12 months of age 5
fold, versus 11-fold in older children. The combination of stunting, wasting and
underweight was closely associated to mortality. Stunting alone (not combined
with wasting) did not significantly increase the mortality risk. CONCLUSIONS:
Sex, severe edema and wasting are predictors of mortality in malnourished
children. Regardless of these factors, children with deficiencies referred to
weight for height and weight for age present a greater mortality risk in
comparison with children who present stunting only.
PMID- 28417876
TI - Insulin resistance and beta-cell function in Colombian mestizo and Embera-Chami
populations and their relation with adiposity degree.
AB - BACKGROUND AND OBJECTIVE: Insulin resistance (IR) is a condition favored by
metabolic and endocrine changes experienced by adipose tissue in the context of
obesity. The prevalence and the presentation of both IR and obesity vary among
the populations, and may be affected by ancestral genetic composition among other
factors. The aim of this study was to compare the presence of IR and obesity in
Amerindians of the Embera-Chami ethnicity and Colombian mestizo population.
PATIENTS AND METHODS: A sample of 630 individuals, 471 mestizos and 159
Amerindians of the Embera-Chami ethnicity, from the general population of
Colombia were studied. For each participant, anthropometric and biochemical
measurements, as well as blood pressure and the Homeostatic Model Assessment
(HOMA) of IR and beta-cell function (%B) were recorded. These values were
compared between the two populations. RESULTS: While prevalence of central
obesity was similar in both populations (48.7% and 42.6% in the mestizo and
Embera groups respectively; p=0.148), body mass index (BMI) values suggested a
higher prevalence of overweight in the Embera than in mestizo population (43.4%
Embera, 31.8% mestizo; p=0.027). Despite the similarities in the prevalence of
HOMA-IR and HOMA-%B status between both populations, the Embera population had a
significantly greater pancreatic beta-cell function, higher insulin levels, and
better glucose control, across BMI and central obesity categories, than the
mestizo population. CONCLUSION: There are differences in aspects related to
energy metabolism between the samples of the mestizo and Amerindian populations
analyzed.
PMID- 28417877
TI - Tobacco and diabetes: clinical relevance and approach to smoking cessation in
diabetic smokers.
AB - Smoking is, together with diabetes mellitus, one of the main risk factors for
cardiovascular disease. Diabetic patients have unique features and
characteristics, some of which are not well known, that cause smoking to
aggravate the effects of diabetes and impose difficulties in the smoking
cessation process, for which a specificand more intensive approach with stricter
controls is required. This review details all aspects with a known influence on
the interaction between smoking and diabetes, both as regards the increased risk
of macrovascular and microvascular complications of diabetes and the factors with
an impact on the results of smoking cessation programs. The treatment guidelines
for these smokers, including the algorithms and drug treatment patterns which
have proved most useful based on scientific evidence, are also discussed.
PMID- 28417879
TI - Comments on "Carcinoma de tiroides incidental versus no incidental: presentacion
clinica, tratamiento quirurgico y pronostico".
PMID- 28417878
TI - Comments on "Incidental versus non-incidental thyroid carcinoma: Clinical
presentation, surgical management and prognosis".
PMID- 28417880
TI - The Japan Prosthodontic Society is establishing the Journal of Prosthodontic
Research (JPR) Best Paper Award.
PMID- 28417881
TI - Understanding GPCR signaling in the brain- the path to CNS drug discovery.
PMID- 28417883
TI - From the Editor's desk...: May 2017.
PMID- 28417884
TI - Farewell from the EASL Secretary General.
PMID- 28417882
TI - EASL Clinical Practical Guidelines on the management of acute (fulminant) liver
failure.
AB - The term acute liver failure (ALF) is frequently applied as a generic expression
to describe patients presenting with or developing an acute episode of liver
dysfunction. In the context of hepatological practice, however, ALF refers to a
highly specific and rare syndrome, characterised by an acute abnormality of liver
blood tests in an individual without underlying chronic liver disease. The
disease process is associated with development of a coagulopathy of liver
aetiology, and clinically apparent altered level of consciousness due to hepatic
encephalopathy. Several important measures are immediately necessary when the
patient presents for medical attention. These, as well as additional clinical
procedures will be the subject of these clinical practice guidelines.
PMID- 28417885
TI - EASL Recognition Award Recipient 2017: Prof. Gustav Paumgartner.
PMID- 28417886
TI - EASL Recognition Award Recipient 2017: Prof. Giorgina Mieli-Vergani.
PMID- 28417887
TI - EASL International Recognition Award Recipient 2017: Professor Kenjiro Wake.
PMID- 28417888
TI - General Concepts of Patient Safety for the Oral and Maxillofacial Surgeon.
AB - Whether managing patients in private offices or as part of a care team at
hospitals, oral and maxillofacial surgeons owe it to patients to understand
medical error and take action to reduce its frequency and adverse effects. This
article reviews general concepts of patient safety, including high-reliability
organization, crew resource management, simulation training, root cause analysis,
and just culture.
PMID- 28417889
TI - Monitoring for the Oral and Maxillofacial Surgeon.
AB - Parenteral medications are titrated in the oral and maxillofacial surgery office
to achieve moderate sedation, deep sedation, or general anesthesia while
continuously maintaining spontaneous ventilation with an open airway. After
initial drug administration, the provider assesses and interprets both the level
of anesthesia and the presence/severity of adverse side effects, both of which
guide further drug titration, cessation, reversal, or medical management. This
assessment is called monitoring, which guides the conduct of anesthesia delivery
and becomes the essence of this art.
PMID- 28417890
TI - Fire Safety for the Oral and Maxillofacial Surgeon and Surgical Staff.
AB - Fire in the operating room is a life-threatening emergency that demands quick,
efficient intervention. Because the circumstances surrounding fires are generally
well-understood, virtually every operating room fire is preventable. Before every
operating room case, thorough preprocedure "time outs" should address each team
members' awareness of specific fire risks and agreement regarding fire concerns
and emergency actions. Fire prevention centers on 3 constituent parts of the fire
triad necessary for fire formation. Regular fire drills should guide policies and
procedures to prevent surgical fires. Delivering optimal patient care in emergent
situations requires surgical team training, practicing emergency roles, and
specific actions.
PMID- 28417891
TI - Outpatient Anesthetic Safety Considerations for Obstructive Sleep Apnea.
AB - Most patients with obstructive sleep apnea (OSA) are not diagnosed
preoperatively. The STOP-Bang questionnaire may identify patients at risk of OSA,
especially those with severe OSA. Patients with mild to moderate OSA, with
optimized comorbidities, can usually safely undergo outpatient surgery. Patients
with severe OSA, who are not optimized medically, should avoid outpatient
surgery.
PMID- 28417892
TI - Discharge Criteria, Impact of the Patient and the Procedure: What the Oral
Surgeon Should Know.
AB - This article is a concise review of discharge criteria following sedation or
anesthesia relevant to the oral and maxillofacial surgeon. Topics covered include
a general overview of the need for objective discharge criteria, a review of
standardized criteria, and a brief discussion on specific anesthetic, patient,
and surgical factors that can impact the safety of the immediate postoperative
recovery and postdischarge periods.
PMID- 28417893
TI - Equipment Safety, Maintenance and Inspection: What the Oral Surgeon Needs to
Know.
AB - Many oral and maxillofacial surgical procedures are done in an office-based
setting, with many oral and maxillofacial surgeons involved in oversight of
equipment maintenance. Goals in equipment management are to prevent harm to
patients and staff, stay compliant with current regulations, and increase
equipment longevity. This article covers the safety, maintenance, and inspection
related to electrical equipment used in the treatment of patients, autoclaves,
radiograph machines, nitrous oxide and oxygen medical gases, and required back-up
power and lighting. An office should always follow manufacturer's recommendations
regarding maintenance and inspection and document policies and monitoring so
compliance can be assured.
PMID- 28417894
TI - Quality Improvement and Reporting Systems: What the Oral and Maxillofacial
Surgeon Should Know.
AB - Health care is an inherently dangerous environment, and patient safety should be
an explicit goal of oral and maxillofacial surgery. Important components of a
safety program include a nonpunitive safety culture, the implementation of
patient safety practices, standardized incident reporting and adverse event
analysis, regular self-assessment, and internal and external benchmarking.
Implementation of a safety program requires the strong commitment of leadership
and the engagement and empowerment of all employees. Oral and maxillofacial
surgery can become the model dental specialty by implementing patient safety
programs for office-based surgery. The programs could then be used by all dental
practitioners performing oral surgery in the office.
PMID- 28417895
TI - Preface.
PMID- 28417896
TI - Production and Precipitation Hardening of Mg-Ca-Zn-Co Alloy for Tissue
Engineering.
AB - In this study, Mg-Ca-Zn-Co alloy specimens for biomedical applications were
produced by the powder metallurgy method. The Mg-Ca-Zn-Co alloy could be used as
a scaffold material in tissue engineering applications. Electrochemical corrosion
behavior of the specimens was investigated in simulated body fluid environment.
Electrochemical corrosion resistance of the specimens was increased with
increasing Zn and Ca contents of the alloy up to an optimum composition and then
decreased. Optimum values for Ca and Zn additions were about 0.7 wt.% and 3.0
wt.% respectively. Young's modulus values of the specimens were determined by
nondestructive ultrasonic measurement. Alloying element addition increased the
Young's modulus of the specimens. Precipitation hardening of the Mg-Ca-Zn-Co
alloy increased the Young's modulus and the corrosion rate of the specimens.
PMID- 28417897
TI - Oral magnesium supplementation reduces the incidence of gastrointestinal
complications following cardiac surgery: a randomized clinical trial.
AB - Gastrointestinal complications are common after coronary artery bypass graft
surgery. These complications are ranged from nausea and vomiting to mesenteric
ischemia and liver failure. It seems that nausea, vomiting, and constipation are
related to magnesium deficiency. This study was designed to examine the effect of
oral magnesium supplementation on the incidence of gastrointestinal complications
in patients undergoing cardiac surgery. In a single blinded randomized clinical
trial, 102 patients who were undergoing coronary artery bypass graft surgery were
randomly allocated into two groups, 52 patients in the intervention and 50
patients in control group. Patients in the experimental group received 800
milligram magnesium oxide (2 tablets each of them containing 240 mg elemental
magnesium) daily from the admission to discharge from hospital. The incidence of
post-operative nausea and vomiting, constipation, and atrial fibrillation was
compared between the groups. Our results showed that postoperative hypomagnesemia
is present in 41.20 and 70.80 percent of the patients in the intervention and
control group patients, respectively. The overall incidence of constipation was
62%. Patients who received magnesium supplementation experienced less atrial
fibrillation, nausea, vomiting, and constipation. Our data showed that oral
magnesium supplementation could reduce the postoperative complications. Despite
the better status in the intervention group, the hypomagnesemia was present in
many of intervention group patients. It seems that supplementation with higher
doses is needed.
PMID- 28417898
TI - Nanoscale influence on photoluminescence and third order nonlinear susceptibility
exhibited by ion-implanted Pt nanoparticles in silica.
AB - A systematic study has been carried out to investigate photoluminescence and
third order nonlinear ultraviolet properties exhibited by platinum nanoparticles
nucleated in a high-purity silica matrix. The modification in the characteristic
photoluminescence spectra of the nanocomposites, ranging between 400 and 600 nm,
was obtained with the assistance of a thermal annealing process that changed the
average size of the platinum nanoparticles. The influence of temperature, between
200 degrees C-1100 degrees C, during the thermal treatment of the
nanostructures was analyzed. UV-vis spectroscopy studies corroborated changes in
the optical absorption resonances of the ion-implanted samples after annealing,
which could then be correlated with the average size of the nanoparticles. The
estimated average size was also corroborated by transmision electron microscopy.
For temperatures below 600 degrees C the system is mainly composed of ultra
small photoluminescent platinum nanoparticles. Larger platinum nanoparticles were
formed at higher annealing temperatures but photoluminescence quenching was
observed as the typical plasmonics response of larger metal nanoparticles started
to emerge. The photoluminescence emission for samples with a particle size of
less than 2 nm is enhanced approximately 12 fold with respect to the samples with
a particle size in the range of 3-7 nm. Differences in the resulting
photoluminescence spectra were revealed by substituting the participation of
argon, hydrogen or nitrogen, as environmental gases for thermal annealing. A weak
PL emission, featuring 1.5 nW at a laser excitation power of 800 MUW, related to
larger platinum nanoparticles was observed. New emission peaks emerging from the
larger platinum nanoparticles were associated with possible hydrogen adsorption
on the nanoparticles' surface. Third order nonlinear ultraviolet measurements
were conducted using a time-resolved two-wave mixing method with self-diffraction
at 355 nm wavelength. The observed self-diffraction decay time is less than 25
ps, regardless of the average size of the nanoparticles studied. The evolution of
the self-diffracted intensities derived from temperature was also linked to the
mean size of the nanoparticles in the samples. Comparative two-wave mixing
evaluations also validated a modification in third order nonlinear susceptibility
exhibited by annealed samples. An important role of the localized surface plasmon
resonance phenomena associated with the platinum nanoparticles for
photoluminescence and optical nonlinearities was identified. A proposed
hypothetical electronic mechanism that may explain the exceptional optical
transitions related to low-dimensional platinum systems is discussed.
PMID- 28417899
TI - Synergistic interaction between pseudocapacitive Fe3O4 nanoparticles and highly
porous silicon carbide for high-performance electrodes as electrochemical
supercapacitors.
AB - Composites of micro- and mesoporous SiC flakes (SiCF) and ferroferric oxide
(Fe3O4), SiCF/Fe3O4, were prepared via the chemical deposition of Fe3O4 on SiCF
by the chemical reduction of an Fe precursor. The SiCF/Fe3O4 electrodes were
fabricated at different Fe3O4 feeding ratios to determine the optimal Fe3O4
content that can maintain a high total surface area of SiCF/Fe3O4 composites as
well as cause a vigorous redox reaction, thereby maximizing the synergistic
effect between the electric double-layer capacitive effects of SiCF and the
pseudo-capacitive effects of Fe3O4. The SiCF/Fe3O4 electrode fabricated with a
Fe3O4/SiCF feeding ratio of 1.5:1 (SiCF/Fe3O4(1.5)) exhibited the highest charge
storage capacity, showing a specific capacitance of 423.2 F g-1 at a scan rate of
5 mV s-1 with a rate performance of 81.8% from 5 to 500 mV s-1 in an aqueous 1 M
KOH electrolyte. The outstanding capacitive performance of the SiCF/Fe3O4(1.5)
electrode could be attributed to the harmonious synergistic effect between the
electric double-layer capacitive contribution of the SiCF and the
pseudocapacitive contribution of the Fe3O4 nanoparticles introduced on the SiCF
surface. These encouraging results demonstrate that the SiCF/Fe3O4(1.5) electrode
is a promising high-performance electrode material for use in supercapacitors.
PMID- 28417900
TI - Green approach to photoluminescent carbon dots for imaging of gram-negative
bacteria Escherichia coli.
AB - Fluorescent carbon dots, zero-dimensional nanomaterials with surface ligands,
have been studied extensively over the past few years in biolabelling or
fluorescence-based live cell assays. In the past, synthetic organic dyes have
been used as cell tracking materials, but they have severe limitations;
fluorescent carbon dots may pave the way to biolabelling and cell imaging. In
this work, green fluorescent carbon dots have been synthesized from a green
source, gram, without any sort of covalent or ionic modifications. These gram
derived carbon dots are unique with respect to synthetic commercial cell-tracking
dyes as they are non-toxic, cell internalization occurs quickly, and they have
excellent bioconjugation with bacterial cells. Our aim is to establish these
carbon dots in a biolabelling assay with its other physicochemical features like
the tunable luminescence property, high degree of water solubility and low
toxicity, towards various environments (wide range of pH, high ionic strength).
Our study introduces a new perspective on the commercialization of carbon dots as
a potential alternative to synthetic organic dyes for fluorescence-based cell
labelling assays.
PMID- 28417901
TI - Tunable bending stiffness of MoSe2/WSe2 heterobilayers from flexural wrinkling.
AB - Understanding the mechanical behaviors of van der Waals heterogeneous 2D
materials is important for their actual applications. Our extensive first
principles calculations and continuum mechanical modeling on the wrinkling of
MoSe2/WSe2 heterobilayers caused by compression reveal that the bending stiffness
of MoSe2/WSe2 wrinkles strongly depend on the wrinkle structures, which first
increase and then decrease with increasing the compressive strain. The bending
stiffness of MoSe2/WSe2 wrinkles could be effectively mediated and tuned by
adjusting the wrinkle geometry and size. The underlying mechanisms are elucidated
by the differences in electronic structures and bonding states at the top, middle
and bottom parts of the wrinkles, and the relevance of the changes of bond
lengths to flexural deformation. Our results suggest a feasible way to develop
flexible devices and nanoelectromechanical systems by utilizing the correlation
and coupling between the mechanical and electronic properties in MoSe2/WSe2
wrinkles.
PMID- 28417902
TI - A NIR fluorescent probe for the rapid detection of Hg2+ in living cells and in
vivo mice imaging.
AB - A near-infrared fluorescent probe NIR-Hg, for the detection of Hg2+ ion, has been
synthesized directly by condensing Changsha dye with 4-Phenyl-3-thiosemicarbazide
and the structure has fully characterized by 1HNMR, 13CNMR, and ESI-MS. The probe
has been designed on the basis of the reaction that Hg2+ ion promotes
thiosemicarbazide to oxazole in aqueous media and had been induced to produce
turn-on fluorescence via an irreversible spirolactam ring-opening process. The
probe NIR-Hg has exhibited fast response (1 min), high sensitivity with 44-fold
fluorescence intensity enhancement under six equivalent amounts of Hg2+ added,
high selectivity over other related metal ions and a low detection limit of 5.8 *
10-8 M in the phosphate buffer. The linear response range covers the
concentration of Hg2+ from 5 * 10-7 to 5 * 10-6 M. In addition, the probe has
good cell-membrane permeability, which is suitable for fluorescence imaging for
Hg2+ in living cells and in vivo mice.
PMID- 28417903
TI - An Assessment of the Potential Use of BNNTs for Boron Neutron Capture Therapy.
AB - Currently, nanostructured compounds have been standing out for their optical,
mechanical, and chemical features and for the possibilities of manipulation and
regulation of complex biological processes. One of these compounds is boron
nitride nanotubes (BNNTs), which are a nanostructured material analog to carbon
nanotubes, but formed of nitrogen and boron atoms. BNNTs present high thermal
stability along with high chemical inertia. Among biological applications, its
biocompatibility, cellular uptake, and functionalization potential can be
highlighted, in addition to its eased utilization due to its nanometric size and
tumor cell internalization. When it comes to new forms of therapy, we can draw
attention to boron neutron capture therapy (BNCT), an experimental radiotherapy
characterized by a boron-10 isotope carrier inside the target and a thermal
neutron beam focused on it. The activation of the boron-10 atom by a neutron
generates a lithium atom, a gamma ray, and an alpha particle, which can be used
to destroy tumor tissues. The aim of this work was to use BNNTs as a boron-10
carrier for BNCT and to demonstrate its potential. The nanomaterial was
characterized through XRD, FTIR, and SEM. The WST-8 assay was performed to
confirm the cell viability of BNNTs. The cells treated with BNNTs were irradiated
with the neutron beam of a Triga reactor, and the apoptosis caused by the
activation of the BNNTs was measured with a calcein AM/propidium iodide test. The
results demonstrate that this nanomaterial is a promising candidate for cancer
therapy through BNCT.
PMID- 28417904
TI - Zebrafish as an Alternative Vertebrate Model for Investigating Developmental
Toxicity-The Triadimefon Example.
AB - Triadimefon is a widely used triazole fungicide known to cause severe
developmental defects in several model organisms and in humans. The present study
evaluated in detail the developmental effects seen in zebrafish embryos exposed
to triadimefon, confirmed and expanded upon previous phenotypic findings and
compared them to those observed in other traditional animal models. In order to
do this, we exposed embryos to 2 and 4 ug/mL triadimefon and evaluated growth
until 120 h post-fertilization (hpf) through gross morphology examination. Our
analysis revealed significant developmental defects at the highest tested
concentration including somite deformities, severe craniofacial defects, a cleft
phenotype along the three primary neural divisions, a rigorously hypoplastic or
even absent mandible and a hypoplastic morphology of the pharyngeal arches.
Interestingly, massive pericardial edemas, abnormal shaped hearts, brachycardia
and inhibited or absent blood circulation were also observed. Our results
revealed that the presented zebrafish phenotypes are comparable to those seen in
other organism models and those derived from human observations as a result of
triadimefon exposure. We therefore demonstrated that zebrafish provide an
excellent system for study of compounds with toxic significance and can be used
as an alternative model for developmental toxicity studies to predict effects in
mammals.
PMID- 28417905
TI - Analytical Criticalities Associated to Different Immunological Methods for Serum
Free Light Chain Detection in Plasma Cell Dyscrasias: A Description of Particular
Clinical Cases.
AB - Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal
gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma
(SMM) are included in the 2003 guidelines by the International Myeloma Working
Group (IMWG). An updated version was then published in 2014, highlighting the
importance of serum free light chain (sFLC) detection, as well as the
kappa/lambda ratio as excellent indicators of clonality. At present, two
commercial assays for sFLC quantification are available: the FreeliteTM assay and
the N-Latex assay. The first was developed by The Binding Site based on a mixture
of polyclonal antibodies directed against a variety of FLC epitopes. It may be
run on a wide range of nephelometers, as well as on turbidimeters. The second
method was developed by Siemens and runs exclusively on Siemens instruments. It
employs a probe mixture of mouse monoclonal antibodies. The aim of our study was
to evaluate sFLC measurement and calculated kappa/lambda ratio in 85 patients
with monoclonal gammopathies (MGs) in order to compare methods. We demonstrated
that there is only a moderate concordance between the two FLC assays. In
particular, in one case, we observed no qualitative alterations of the serum
protein pattern, and in the absence of a FreeliteTM assay, sFLC measurement would
not have been possible to highlight the increase of lambda FLC.
PMID- 28417906
TI - Random Finite Set Based Bayesian Filtering with OpenCL in a Heterogeneous
Platform.
AB - While most filtering approaches based on random finite sets have focused on
improving performance, in this paper, we argue that computation times are very
important in order to enable real-time applications such as pedestrian detection.
Towards this goal, this paper investigates the use of OpenCL to accelerate the
computation of random finite set-based Bayesian filtering in a heterogeneous
system. In detail, we developed an efficient and fully-functional pedestrian
tracking system implementation, which can run under real-time constraints,
meanwhile offering decent tracking accuracy. An extensive evaluation analysis was
carried out to ensure the fulfillment of sufficient accuracy requirements. This
was followed by extensive profiling analysis to spot the potential bottlenecks in
terms of execution performance, which were then targeted to come up with an
OpenCL accelerated application. Video-throughput improvements from roughly 15 fps
to 100 fps (6*) were observed on average while processing typical MOT benchmark
videos. Moreover, the worst-case frame processing yielded an 18* advantage from
nearly 2 fps to 36 fps, thereby comfortably meeting the real-time constraints.
Our implementation is released as open-source code.
PMID- 28417907
TI - A Classification Method for Seed Viability Assessment with Infrared Thermography.
AB - This paper presents a viability assessment method for Pisum sativum L. seeds
based on the infrared thermography technique. In this work, different artificial
treatments were conducted to prepare seeds samples with different viability.
Thermal images and visible images were recorded every five minutes during the
standard five day germination test. After the test, the root length of each
sample was measured, which can be used as the viability index of that seed. Each
individual seed area in the visible images was segmented with an edge detection
method, and the average temperature of the corresponding area in the infrared
images was calculated as the representative temperature for this seed at that
time. The temperature curve of each seed during germination was plotted. Thirteen
characteristic parameters extracted from the temperature curve were analyzed to
show the difference of the temperature fluctuations between the seeds samples
with different viability. With above parameters, support vector machine (SVM) was
used to classify the seed samples into three categories: viable, aged and dead
according to the root length, the classification accuracy rate was 95%. On this
basis, with the temperature data of only the first three hours during the
germination, another SVM model was proposed to classify the seed samples, and the
accuracy rate was about 91.67%. From these experimental results, it can be seen
that infrared thermography can be applied for the prediction of seed viability,
based on the SVM algorithm.
PMID- 28417909
TI - Interactions among the Predatory Midge Aphidoletes aphidimyza (Diptera:
Cecidomyiidae), the Fungal Pathogen Metarhizium brunneum (Ascomycota:
Hypocreales), and Maize-Infesting Aphids in Greenhouse Mesocosms.
AB - The generalist entomopathogenic fungus, Metarhizium brunneum, has proved to have
great potential as a versatile biological pest control agent. The gall midge
Aphidoletes aphidimyza is a specialist predator that occurs naturally in Europe
and has been successfully used for aphid suppression. However, the interaction
between these two biological control organisms and how it may affect the
biological control of aphids awaits further investigation. As part of the EU
supported project INBIOSOIL, this study was conducted in greenhouse conditions to
assess the possible effects of combining both biological control agents. In a
randomized complete block design, sweet corn (Zea mays var. saccharata) plants
were grown in large pots filled with natural soil or natural soil inoculated with
M. brunneum. At the third leaf stage, before being individually caged, plants
were infested with Rhopalosiphum padi and A. aphidimyza pupae were introduced in
the soil. Aphidoletes aphidimyza midge emergence, number of living midges and
number of aphids were recorded daily. The presence of conidia in the soil and on
leaves was assessed during the experiment. At the conclusion of the experiment,
the number of live aphids and their developmental stage, consumed aphids, and A.
aphidimyza eggs was assessed under stereomicroscope. This study's findings showed
that the presence of M. brunneum did not affect A. aphidimyza midge emergence.
However, longevity was significantly affected. As the study progressed,
significantly fewer predatory midges were found in cages treated with M. brunneum
compared to untreated cages. Furthermore, by the end of the study, the number of
predatory midges found in the Metarhizium-treated cages was four times lower than
in the untreated cages. Both daily and final count of aphids were significantly
affected by treatment. Aphidoletes aphidimyza applied alone suppressed the aphid
population more effectively than M. brunneum applied alone. Additionally, the
aphid population was most suppressed when both agents were combined, though the
suppression was less than additive.
PMID- 28417908
TI - Cytokinesis Failure Leading to Chromosome Instability in v-Src-Induced
Oncogenesis.
AB - v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active
variant of c-Src. Activation of Src is observed frequently in colorectal and
breast cancers, and is critical in tumor progression through multiple processes.
However, in some experimental conditions, v-Src causes growth suppression and
apoptosis. In this review, we highlight recent progress in our understanding of
cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src
expressing cells. v-Src induces cell cycle changes-such as the accumulation of
the 4N cell population-and increases the number of binucleated cells, which is
accompanied by an excess number of centrosomes. Time-lapse analysis of v-Src
expressing cells showed that cytokinesis failure is caused by cleavage furrow
regression. Microscopic analysis revealed that v-Src induces delocalization of
cytokinesis regulators including Aurora B and Mklp1. Tetraploid cell formation is
one of the causes of chromosome instability; however, tetraploid cells can be
eliminated at the tetraploidy checkpoint. Interestingly, v-Src weakens the
tetraploidy checkpoint by inhibiting the nuclear exclusion of the transcription
coactivator YAP, which is downstream of the Hippo pathway and its nuclear
exclusion is critical in the tetraploidy checkpoint. We also discuss the
relationship between v-Src-induced chromosome instability and growth suppression
in v-Src-induced oncogenesis.
PMID- 28417910
TI - Effects of Three Commercially Available Sports Drinks on Substrate Metabolism and
Subsequent Endurance Performance in a Postprandial State.
AB - Purpose: To examine the effects of commercially available sports beverages with
various components on substrate metabolism and subsequent performance. Methods:
Two studies were conducted in a double-blinded, counterbalanced manner. Study I
was designed to determine the glycemic index, while study II determined the
utilization of substrates and subsequent exercise performance. Ten healthy male
participants (age 21.70 +/- 2.41 years, height 176.60 +/- 5.23 cm, weight 66.58
+/- 5.38 kg, VO2max 48.1 +/- 8.4 mL/kg/min) participated in both study I and
study II. Three types of commercially available sports beverage powders were
used. The powders consisted primarily of oligosaccharides (low molecular weight
carbohydrates, L-CHO), hydrolyzed starch (high molecular weight CHO, H-CHO), and
whey protein powder with carbohydrate (CHO-PRO). They were dissolved in purified
water with identical CHO concentration of 8% (w/v). In study I, each participant
underwent two oral glucose tolerance tests (OGTT) and one glycemic response test
for each sports drink. In study II, participants cycled for 60 min at 70% VO2max,
one hour after consuming a standardized breakfast. One of four prescribed
beverages (L-CHO, H-CHO, CHO-PRO, and Placebo control, PLA) was served at 0, 15,
30, 45 min during the exercise. Six hours after the first exercise session,
participants came back for a "time to exhaustion test" (TTE). Blood samples were
drawn at 0, 30, and 60 min in the first exercise session, while arterial blood
gas analysis was conducted at 0, 30, and 60 min in both sessions. Subjective
feelings (rating of perceived exertion and abdominal discomfort) were also
evaluated every 30 min during exercise. Results: Compared to the reference
standardized glucose solution, the glycemic index of the L-CHO beverage was
117.70 +/- 14.25, while H-CHO was 105.50 +/- 12.82, and CHO-PRO was 67.23 +/-
5.88. During the exercise test, the insulin level at 30 and 60 min was
significantly lower than baseline following the treatment of L-CHO, H-CHO, and
PLA (p < 0.05). The CHO oxidation rate at 60 min in the first exercise session
was significantly higher than that at 60 min in the second exercise session
following the L-CHO treatment (p < 0.05). Time to exhaustion was not
significantly different (p > 0.05). Conclusion: The CHO sports beverage with
additional PRO maintains insulin production during endurance cycling at 70%
VO2max in the postprandial state. L-CHO sports beverage suppresses fat
utilization during the subsequent exercise performance test. The subsequent
exercise performance (as evaluated by TTE) was not influenced by the type of CHO
or the addition of PRO in the commercially available sports beverages used in the
present study.
PMID- 28417911
TI - Genome-Wide Analyses of the Soybean F-Box Gene Family in Response to Salt Stress.
AB - The F-box family is one of the largest gene families in plants that regulate
diverse life processes, including salt responses. However, the knowledge of the
soybean F-box genes and their roles in salt tolerance remains limited. Here, we
conducted a genome-wide survey of the soybean F-box family, and their expression
analysis in response to salinity via in silico analysis of online RNA-sequencing
(RNA-seq) data and quantitative reverse-transcription polymerase chain reaction
(qRT-PCR) to predict their potential functions. A total of 725 potential F-box
proteins encoded by 509 genes were identified and classified into 9 subfamilies.
The gene structures, conserved domains and chromosomal distributions were
characterized. There are 76 pairs of duplicate genes identified, including genome
wide segmental and tandem duplication events, which lead to the expansion of the
number of F-box genes. The in silico expression analysis showed that these genes
would be involved in diverse developmental functions and play an important role
in salt response. Our qRT-PCR analysis confirmed 12 salt-responding F-box genes.
Overall, our results provide useful information on soybean F-box genes,
especially their potential roles in salt tolerance.
PMID- 28417912
TI - Electrospun Fiber Pads of Cellulose Acetate and Essential Oils with Antimicrobial
Activity.
AB - The method of electrospinning was used to create nanofibers made of cellulose
acetate (CA) and essential oils (EOs). CA polymer at 15% w/v was dissolved in
acetone and then 1% or 5% v/v of EOs was added to the polymer solution. The
utilized essential oils were rosemary and oregano oils. Then, the CA/EOs in
acetone solution were electrospun, creating micro/nanofibers, approximately 700
1500 nm in diameter. Raman spectroscopy was used to detect the attachment of the
EOs in the CA electrospun fibers (ESFs). Scanning electron microscopy was used to
study the morphology, topography and dimensions of the ESFs. The formed CA/EOs
ESFs are found to have good antimicrobial properties against three common
microbial species, frequently found in difficult to treat infections: Bacteria
species Staphylococcus aureus, Escherichia coli and the yeast Candida albicans.
ESFs with 5% v/v oregano oil with respect to the initial solution, showed the
best antimicrobial and anti-biofilm effects due to the potency of this EO against
bacteria and fungi, especially for Escherichia coli and Candida albicans. This
work describes an effective and simple method to prepare CA/EOs ESFs and opens up
many new applications of micro/nanofibers such as improved antimicrobial wound
dressings, anti-biofilm surfaces, sensors and packaging alternatives.
PMID- 28417913
TI - Comparative Study on the Antivirus Activity of Shuang-Huang-Lian Injectable
Powder and Its Bioactive Compound Mixture against Human Adenovirus III In Vitro.
AB - Shuang-Huang-Lian injectable powder (SHL)-a classical purified herbal preparation
extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense
has been used against human adenovirus III (HAdV3) for many years. The
combination herb and its major bioactive compounds, including chlorogenic acid,
baicalin, and forsythia glycosides A, are effective inhibitors of the virus.
However, no comprehensive studies are available on the antiviral effects of SHL
against HAdV3. Moreover, it remains unclear whether the mixture of chlorogenic
acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity
compared with SHL. Therefore, a comparative study was performed to investigate
the combination which is promising for further antiviral drug development. To
evaluate their antivirus activity in parallel, the combination ratio and dose of
CBF were controlled and consistent with SHL. First, the fingerprint and the ratio
of CBF in SHL were determined by high performance liquid chromatography. Then, a
plaque reduction assay, reverse transcription polymerase chain reaction (PCR),
real-time polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay
(ELISA) were used to explore its therapeutic effects on viral infection and
replication, respectively. The results showed that SHL and CBF inhibited dose-
and time-dependently HAdV3-induced plaque formation in A549 and HEp-2 cells. SHL
was more effective than CBF when supplemented prior to and after viral
inoculation. SHL prevented viral attachment, internalization, and replication at
high concentration and decreased viral levels within and out of cells at non
toxic concentrations in both cell types. Moreover, the expression of tumor
necrosis factor alpha (TNF)-alpha, interleukin (IL)-1beta, and IL-6 was lower and
the expression of interferon (IFN)-gamma was higher in both cell types treated
with SHL than with CBF. In conclusion, SHL is much more effective and slightly
less toxic than CBF.
PMID- 28417914
TI - Interactions of the Insulin-Like Growth Factor Axis and Vitamin D in Prostate
Cancer Risk in the Prostate Cancer Prevention Trial.
AB - Some, but not all, epidemiologic studies report an association between vitamin D
and prostate cancer risk. The inconsistent findings might be explained in the
context of modification by members of the insulin-like growth factor (IGF) axis.
Data and specimens for this nested case-control study (n = 1695 cases and n =
1682 controls) are from the Prostate Cancer Prevention Trial (PCPT). Baseline
serum samples were assayed for 25(OH)D, IGF-1, IGF-2, IGFBP-2, IGFBP-3, and the
ratio of IGF1:BP3, along with insulin-related markers c-peptide and leptin. The
presence of prostate cancer was assessed by prostate biopsy. Multivariate
logistic regression was used to estimate odds ratios (OR) and 95% confidence
intervals (CIs) for prostate cancer risk. There were no interactions between
serum 25(OH)D and IGF analytes in relation to prostate cancer risk when PCPT
treatment arms were combined. In the placebo arm, above median serum 25(OH)D
levels were associated with increased risk of prostate cancer among men with
higher IGF-2 (OR:1.33, 95% CI: 1.00-1.65), with a significant interaction between
25(OH)D and treatment arm (Pinteraction = 0.04). Additionally, there was an
interaction between treatment arm and serum IGFBP-3 (Pinteraction = 0.03). Higher
serum 25(OH)D may increase risk of prostate cancer in the presence of higher
circulating IGF-2.
PMID- 28417915
TI - High Glucose Accelerates Cell Proliferation and Increases the Secretion and mRNA
Expression of Osteopontin in Human Pancreatic Duct Epithelial Cells.
AB - BACKGROUND: The incidence of pancreatic cancer is increasing year-by-year in
Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most
common. Recently, it has become evident that patients suffering from diabetes and
obesity show increased expression of osteopontin (OPN). The purpose of this study
was to investigate the effect of high glucose and high insulin culture conditions
on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly
on OPN expression. METHODS: HPDE-6 were cultured under various conditions,
employing several combinations of glucose (normal, 6 mM high, 30 mM, and 60 mM)
and insulin (0.1 nM, 1 nM) concentration. RESULTS: HPDE-6 cell proliferation was
significantly accelerated under high glucose culture conditions in comparison to
samples in 6 mM glucose, and was more prominent under high insulin conditions. At
the same time, the expression of OPN mRNA was also increased significantly. In
comparison with 6 mM glucose, the expression of 8-OHdG DNA was increased in high
glucose culture. CONCLUSION: HPDE-6 cells show accelerated proliferation and
increased OPN expression when cultured under high glucose and high insulin
conditions. Furthermore, the cells show increased oxidative stress in the
presence of high glucose.
PMID- 28417916
TI - Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene
Structure, Differential Expression and Phylogenetic Analysis.
AB - Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions
such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene
structure and evolution, we cloned seven Paracentrotus lividus MT genes,
comparing them to Echinodermata and Chordata genes. Moreover, we performed a
phylogenetic analysis of 32 MTs from different classes of echinoderms and 13 MTs
from the most ancient chordates, highlighting the relationships between them.
Since MTs have multiple roles in the cells, we performed RT-qPCR and in situ
hybridization experiments to understand better MT functions in sea urchin
embryos. Results showed that the expression of MTs is regulated throughout
development in a cell type-specific manner and in response to various metals. The
MT7 transcript is expressed in all tissues, especially in the stomach and in the
intestine of the larva, but it is less metal-responsive. In contrast, MT8 is
ectodermic and rises only at relatively high metal doses. MT5 and MT6 expression
is highly stimulated by metals in the mesenchyme cells. Our results suggest that
the P. lividus MT family originated after the speciation events by gene
duplications, evolving developmental and environmental sub-functionalization.
PMID- 28417917
TI - Minicircle Mediated Gene Delivery to Canine and Equine Mesenchymal Stem Cells.
AB - Gene-directed tissue repair offers the clinician, human or veterinary, the chance
to enhance cartilage regeneration and repair at a molecular level. Non-viral
plasmid vectors have key biosafety advantages over viral vector systems for
regenerative therapies due to their episomal integration however, conventional
non-viral vectors can suffer from low transfection efficiency. Our objective was
to identify and validate in vitro a novel non-viral gene expression vector that
could be utilized for ex vivo and in vivo delivery to stromal-derived mesenchymal
stem cells (MSCs). Minicircle plasmid DNA vector containing green fluorescent
protein (GFP) was generated and transfected into adipose-derived MSCs from three
species: canine, equine and rodent and transfection efficiency was determined.
Both canine and rat cells showed transfection efficiencies of approximately 40%
using minicircle vectors with equine cells exhibiting lower transfection
efficiency. A Sox9-expressing minicircle vector was generated and transfected
into canine MSCs. Successful transfection of the minicircle-Sox9 vector was
confirmed in canine cells by Sox9 immunostaining. This study demonstrate the
application and efficacy of a novel non-viral expression vector in canine and
equine MSCs. Minicircle vectors have potential use in gene-directed regenerative
therapies in non-rodent animal models for treatment of cartilage injury and
repair.
PMID- 28417919
TI - SUMO-Specific Cysteine Protease 1 Promotes Epithelial Mesenchymal Transition of
Prostate Cancer Cells via Regulating SMAD4 deSUMOylation.
AB - In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific
cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in
regulating deSUMOylation of TGF-beta/SMADs signaling is unknown. In this study,
we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate
cancer cells with high metastatic characteristics (PC3M). Likewise, we also
created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate
cancer cells with low metastatic potential (LNCaP). We showed that silencing of
SENP1 promoted cellular apoptosis, and inhibited proliferation and migration of
PC3M cells. Moreover, SENP1 silencing increased the SMAD4 expression at protein
level, up-regulated E-cadherin and down-regulated Vimentin expression, indicating
the inhibition of epithelial mesenchymal transition (EMT). Furthermore, SMAD4
interference abolished SENP1-mediated up-regulation of E-cadherin, suggesting
that SENP1 regulated E-cadherin expression via SMAD4. SENP1 over-expression in
LNCaP cells reduced SMAD4 protein, and promoted EMT via decreasing E-cadherin and
increasing Vimentin. Moreover, down-regulation of SMAD4 and E-cadherin were
blocked, after transfection with two SUMOylation sites mutated SMAD4, suggesting
that SENP1 might reduce SMAD4 levels to regulate E-cadherin expression via
deSUMOylation of SMAD4. In conclusion, SENP1 deSUMOylated SMAD4 to promote EMT
via up-regulating E-cadherin in prostate cancer cells. Therefore, SENP1 is a
potential target for treatment of advanced prostate cancer.
PMID- 28417918
TI - High Prevalence of blaNDM-1, blaVIM, qacE, and qacEDelta1 Genes and Their
Association with Decreased Susceptibility to Antibiotics and Common Hospital
Biocides in Clinical Isolates of Acinetobacter baumannii.
AB - The objective of this study was to evaluate the susceptibility of metallo-beta
lactamase (MBL)-producing Acinetobacter baumannii (A. baumannii) clinical
isolates to biocides. We also determined the prevalence and correlation of efflux
pump genes, class 1 integron and MBL encoding genes. In addition, blaVIM, blaNDM
1, qacE and qacEDelta1 nucleotide sequence analysis was performed and compared to
sequences retrieved from GenBank at the National Center for Biotechnology
Information database. A. baumannii had a resistance rate to carbapenem of 71.4%
and 39.3% and was found to be a MBL producer. The minimum inhibitory
concentrations (MICs) of chlorhexidine and cetrimide were higher than the
recommended concentrations for disinfection in 54.5% and 77.3% of MBL-positive
isolates respectively and their MICs were significantly higher among qac gene
positive isolates. Coexistence of qac genes was detected in 68.1% and 50% of the
isolates with blaVIM and blaNDM-1 respectively. There was a significant
correlation between the presence of qac genes and MBL-encoding blaVIM and blaNDM
1 genes. Each of the blaNDM-1, blaVIM, qacE and qacEDelta1 DNA sequences showed
homology with each other and with similar sequences reported from other
countries. The high incidence of Verona integron-encoded metallo-beta-lactamases
(VIM) and New-Delhi-metallo-beta-lactamase (NDM) and qac genes in A.baumannii
highlights emerging therapeutic challenges for being readily transferable between
clinically relevant bacteria. In addition reduced susceptibility to chlorhexidine
and cetrimide and the potential for cross resistance to some antibiotics
necessitates the urgent need for healthcare facilities to periodically evaluate
biocides efficacy, to address the issue of antiseptic resistance and to initiate
a "biocidal stewardship".
PMID- 28417920
TI - Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human
Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study
and Hepatotoxicity in Humans.
AB - In the development of drugs, we sometimes encounter fatty change of the
hepatocytes (steatosis) which is not accompanied by degenerative change in the
liver in non-clinical toxicity studies. In this study, we investigated the
relationships between fatty change of the hepatocytes noted in non-clinical
toxicity studies of compound X, a candidate compound in drug development, and
mitochondrial dysfunction in order to estimate the potential risk of the compound
to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in
vitro exploratory studies for this purpose. In vivo lipidomics analysis was
conducted to investigate the relationships between alteration of the hepatic
lipids and mitochondrial dysfunction. In the liver of rats treated with compound
X, triglycerides containing long-chain fatty acids, which are the main energy
source of the mitochondria, accumulated. Accumulation of these triglycerides was
considered to be related to the inhibition of mitochondrial respiration based on
the results of in vitro mitochondria toxicity studies. In conclusion, fatty
change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug
candidates can be regarded as a critical finding for the estimation of their
potential risk to induce DILI in humans when the fatty change is induced by
mitochondrial dysfunction.
PMID- 28417921
TI - Bioethics of Clinical Applications of Stem Cells.
AB - The clinical applications of stem cells pose a multitude of problems, including
safety, efficacy, information and consent, the right to unproven treatments, the
"right to try", costs, access, sustainability, scientific scrupulousness, patents
and regulatory aspects, to name but a few. This article does not address
individual issues, but rather introduces and discusses some of the possible
approaches to solving the problems. The first part compares the consequentialist
and deontological approaches, offering an overview of "top-down" and "bottom-up"
models and proposing the principles of personalism as applied in clinical
settings. The second part of the article suggests practical frameworks for
organising the ethical issues, focusing in particular on the medical indications,
patient preferences, quality of life, and contextual features.
PMID- 28417922
TI - Indole Derivatives Isolated from Brown Alga Sargassum thunbergii Inhibit
Adipogenesis through AMPK Activation in 3T3-L1 Preadipocytes.
AB - Seaweed, a popular and abundant food ingredient mainly consumed in Asian
countries, is a good source of bioactive compounds with anti-obesity effects.
However, the anti-obesity effects of Sargassum thunbergii have not yet been
established. In this study, we isolated six indole derivatives (STCs)-indole-2
carboxaldehyde (STC-1), indole-3-carboxaldehyde (STC-2), indole-4-carboxaldehyde
(STC-3), indole-5-carboxaldehyde (STC-4), indole-6-carboxaldehyde (STC-5), and
indole-7-carboxaldehyde (STC-6)-from S. thunbergii and evaluated their inhibitory
effects on adipocyte differentiation in 3T3-L1 cells. We found that STC-1 and STC
5 resulted in non-toxic inhibition of the differentiation of 3T3-L1 adipocytes
and thus selected these compounds for further study. STC-1 and STC-5
significantly inhibited lipid accumulation and downregulated the expression of
peroxisome proliferator-activated receptor-gamma (PPARgamma), CCAAT/enhancer
binding protein alpha (C/EBPalpha), and sterol regulatory element-binding protein
1c (SREBP-1c) in a dose-dependent manner. The specific mechanism mediating the
effects of STC-1 and STC-5 was shown to be AMP-activated protein kinase (AMPK)
activation. Our results demonstrated the inhibitory effect of STC-1 and STC-5 on
adipogenesis through the activation of the AMPK signal pathway. Together, these
findings suggested that STC-1 and STC-5 may be effective candidates for the
prevention of obesity or obesity-related diseases.
PMID- 28417923
TI - Anemia in Kawasaki Disease: Hepcidin as a Potential Biomarker.
AB - Kawasaki disease (KD) is an autoimmune-like disease and acute childhood
vasculitis syndrome that affects various systems but has unknown etiology. In
addition to the standard diagnostic criteria, anemia is among the most common
clinical features of KD patients and is thought to have a more prolonged duration
of active inflammation. In 2001, the discovery of a liver-derived peptide hormone
known as hepcidin began revolutionizing our understanding of anemia's relation to
a number of inflammatory diseases, including KD. This review focuses on hepcidin
induced iron deficiency's relation to transient hyposideremia, anemia, and
disease outcomes in KD patients, and goes on to suggest possible routes of
further study.
PMID- 28417925
TI - A Cost-Effective Geodetic Strainmeter Based on Dual Coaxial Cable Bragg Gratings.
AB - Observations of surface deformation are essential for understanding a wide range
of geophysical problems, including earthquakes, volcanoes, landslides, and
glaciers. Current geodetic technologies, such as global positioning system (GPS),
interferometric synthetic aperture radar (InSAR), borehole and laser
strainmeters, are costly and limited in their temporal or spatial resolutions.
Here we present a new type of strainmeters based on the coaxial cable Bragg
grating (CCBG) sensing technology that provides cost-effective strain
measurements. Two CCBGs are introduced into the geodetic strainmeter: one serves
as a sensor to measure the strain applied on it, and the other acts as a
reference to detect environmental noises. By integrating the sensor and reference
signals in a mixer, the environmental noises are minimized and a lower mixed
frequency is obtained. The lower mixed frequency allows for measurements to be
taken with a portable spectrum analyzer, rather than an expensive spectrum
analyzer or a vector network analyzer (VNA). Analysis of laboratory experiments
shows that the strain can be measured by the CCBG sensor, and the portable
spectrum analyzer can make measurements with the accuracy similar to the
expensive spectrum analyzer, whose relative error to the spectrum analyzer R3272
is less than +/-0.4%. The outputs of the geodetic strainmeter show a linear
relationship with the strains that the CCBG sensor experienced. The measured
sensitivity of the geodetic strainmeter is about -0.082 kHz/MUepsilon; it can
cover a large dynamic measuring range up to 2%, and its nonlinear errors can be
less than 5.3%.
PMID- 28417924
TI - Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells
after Xenograft into Nude Mice.
AB - The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian
tumors resides in a tiny population of cancer cells known as ovarian cancer stem
cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a
great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles
(PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX)
against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an
emulsion solvent evaporation method, supported by incorporation of folic acid
(FA) as the ligand. NPs were characterized for size, surface morphology, drug
loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded
FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral
efficiency and active targeting potential of prepared NPs against tumors in nude
mice were investigated. In vitro results revealed that IC50 of PTX was
significantly reduced after loading on PLGA NPs. On the other hand, in vivo
results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX.
Investigation with real time quantitative PCR analysis revealed the limiting
expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA NPs as a
drug delivery system for PTX. Histopathological examination of tumors showed the
effective biological influence of PTX-loaded FA/PLGA NPs through the appearance
of reactive lymphoid follicles. Targeting potential of PTX was activated by
FA/PLGA NPs through significant preservation of body weight (p < 0.0001) and
minimizing the systemic toxicity in healthy tissues. Immunohistochemical
investigation revealed a high expression of apoptotic markers in tumor tissue,
supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on
FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting
potential against OCSCs.
PMID- 28417926
TI - Fast Noncircular 2D-DOA Estimation for Rectangular Planar Array.
AB - A novel scheme is proposed for direction finding with uniform rectangular planar
array. First, the characteristics of noncircular signals and Euler's formula are
exploited to construct a new real-valued rectangular array data. Then, the
rotational invariance relations for real-valued signal space are depicted in a
new way. Finally the real-valued propagator method is utilized to estimate the
pairing two-dimensional direction of arrival (2D-DOA). The proposed algorithm
provides better angle estimation performance and can discern more sources than
the 2D propagator method. At the same time, it has very close angle estimation
performance to the noncircular propagator method (NC-PM) with reduced
computational complexity.
PMID- 28417927
TI - Wireless Fractal Ultra-Dense Cellular Networks.
AB - With the ever-growing number of mobile devices, there is an explosive expansion
in mobile data services. This represents a challenge for the traditional cellular
network architecture to cope with the massive wireless traffic generated by
mobile media applications. To meet this challenge, research is currently focused
on the introduction of a small cell base station (BS) due to its low transmit
power consumption and flexibility of deployment. However, due to a complex
deployment environment and low transmit power of small cell BSs, the coverage
boundary of small cell BSs will not have a traditional regular shape. Therefore,
in this paper, we discuss the coverage boundary of an ultra-dense small cell
network and give its main features: aeolotropy of path loss fading and fractal
coverage boundary. Simple performance analysis is given, including coverage
probability and transmission rate, etc., based on stochastic geometry theory and
fractal theory. Finally, we present an application scene and discuss challenges
in the ultra-dense small cell network.
PMID- 28417929
TI - Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction
of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in
Thyroid Cancer.
AB - : Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the
context of thyroid cancer for identification of the optimal treatment strategy.
It has exemplarily been shown that DWI at 3T can distinguish undifferentiated
from well-differentiated thyroid carcinoma, which has decisive implications for
the magnitude of surgery. This study used DWI histogram analysis of whole tumor
apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate
thyroid carcinomas which had already gained the capacity to metastasize
lymphatically from those not yet being able to spread via the lymphatic system.
The secondary aim was to reflect prognostically important tumor-biological
features like cellularity and proliferative activity with ADC histogram analysis.
Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph
node status, extent of infiltration of surrounding tissue, and Ki-67 and p53
expression were assessed in these patients. DWI was obtained in a 3T system using
b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a
histogram-based approach. Several ADC parameters showed significant correlations
with immunohistopathological parameters. Most importantly, ADC histogram skewness
and ADC histogram kurtosis were able to differentiate between nodal negative and
nodal positive thyroid carcinoma. CONCLUSIONS: histogram analysis of whole ADC
tumor volumes has the potential to provide valuable information on tumor biology
in thyroid carcinoma. However, further studies are warranted.
PMID- 28417930
TI - Degradation of Methyl 2-Aminobenzoate (Methyl Anthranilate) by H2O2/UV: Effect of
Inorganic Anions and Derived Radicals.
AB - This study shows that methyl 2-aminobenzoate (also known as methyl anthranilate,
hereafter MA) undergoes direct photolysis under UVC and UVB irradiation and that
its photodegradation is further accelerated in the presence of H2O2. Hydrogen
peroxide acts as a source of hydroxyl radicals (.OH) under photochemical
conditions and yields MA hydroxyderivatives. The trend of MA photodegradation
rate vs. H2O2 concentration reaches a plateau because of the combined effects of
H2O2 absorption saturation and .OH scavenging by H2O2. The addition of chloride
ions causes scavenging of .OH, yielding Cl2.- as the most likely reactive
species, and it increases the MA photodegradation rate at high H2O2 concentration
values. The reaction between Cl2.- and MA, which has second-order rate constant k
C l 2 * - + M A = (4.0 +/- 0.3) * 108 M-1.s-1 (determined by laser flash
photolysis), appears to be more selective than the .OH process in the presence of
H2O2, because Cl2.- undergoes more limited scavenging by H2O2 compared to .OH.
While the addition of carbonate causes .OH scavenging to produce CO3.- ( k C O 3
* - + M A = (3.1 +/- 0.2) * 108 M-1.s-1), carbonate considerably inhibits the
photodegradation of MA. A possible explanation is that the elevated pH values of
the carbonate solutions make H2O2 to partially occur as HO2-, which reacts very
quickly with either .OH or CO3.- to produce O2.-. The superoxide anion could
reduce partially oxidised MA back to the initial substrate, with consequent
inhibition of MA photodegradation. Fast MA photodegradation is also observed in
the presence of persulphate/UV, which yields SO4.- that reacts effectively with
MA ( k S O 4 * - + M A = (5.6 +/- 0.4) * 108 M-1.s-1). Irradiated H2O2 is
effective in photodegrading MA, but the resulting MA hydroxyderivatives are
predicted to be about as toxic as the parent compound for aquatic organisms (most
notably, fish and crustaceans).
PMID- 28417928
TI - Potential Coagulation Factor-Driven Pro-Inflammatory Responses in Ovarian Cancer
Tissues Associated with Insufficient O2 and Plasma Supply.
AB - Tissue factor (TF) is a cell surface receptor for coagulation factor VII (fVII).
The TF-activated fVII (fVIIa) complex is an essential initiator of the extrinsic
blood coagulation process. Interactions between cancer cells and immune cells via
coagulation factors and adhesion molecules can promote progression of cancer,
including epithelial ovarian cancer (EOC). This process is not necessarily
advantageous, as tumor tissues generally undergo hypoxia due to aberrant
vasculature, followed by reduced access to plasma components such as coagulation
factors. However, hypoxia can activate TF expression. Expression of fVII,
intercellular adhesion molecule-1 (ICAM-1), and multiple pro-inflammatory
cytokines can be synergistically induced in EOC cells in response to hypoxia
along with serum deprivation. Thus, pro-inflammatory responses associated with
the TF-fVIIa-ICAM-1 interaction are expected within hypoxic tissues. Tumor tissue
consists of multiple components such as stromal cells, interstitial fluid,
albumin, and other micro-factors such as proton and metal ions. These factors,
together with metabolism reprogramming in response to hypoxia and followed by
functional modification of TF, may contribute to coagulation factor-driven
inflammatory responses in EOC tissues. The aim of this review was to describe
potential coagulation factor-driven inflammatory responses in hypoxic EOC
tissues. Arguments were extended to clinical issues targeting this characteristic
tumor environment.
PMID- 28417931
TI - Upstreaming and Normalizing Advance Care Planning Conversations-A Public Health
Approach.
AB - As a society, we simply don't talk about this universal experience called dying
and death; in fact, we ignore it until we have to face it. Thus, it is often in a
crisis experience when we have to make decisions while we are laden with
uncertainty and intense emotions. Sixty percent of people say making sure their
family is not burdened by tough decisions is extremely important, yet 56% of them
have not held a conversation about its context. Instead of waiting to make end-of
life decisions, let us begin to think about what matters most while we are
living, what we value most, and how we translate these values into conversations
about what is important. As a public health concern, if we can upstream the
advance care planning discussion into usual health promotion activities, perhaps,
as a society, we can begin to normalize and reshape how we make decisions about
the last chapters of our lives.
PMID- 28417932
TI - Marine Microbial-Derived Molecules and Their Potential Use in Cosmeceutical and
Cosmetic Products.
AB - The oceans encompass a wide range of habitats and environmental conditions, which
host a huge microbial biodiversity. The unique characteristics of several marine
systems have driven a variety of biological adaptations, leading to the
production of a large spectrum of bioactive molecules. Fungi, fungi-like protists
(such as thraustochytrids) and bacteria are among the marine organisms with the
highest potential of producing bioactive compounds, which can be exploited for
several commercial purposes, including cosmetic and cosmeceutical ones.
Mycosporines and mycosporine-like amino acids, carotenoids, exopolysaccharides,
fatty acids, chitosan and other compounds from these microorganisms might
represent a sustainable, low-cost and fast-production alternative to other
natural molecules used in photo-protective, anti-aging and skin-whitening
products for face, body and hair care. Here, we review the existing knowledge of
these compounds produced by marine microorganisms, highlighting the marine
habitats where such compounds are preferentially produced and their potential
application in cosmetic and cosmeceutical fields.
PMID- 28417933
TI - Radiogenomic Analysis of Oncological Data: A Technical Survey.
AB - In the last few years, biomedical research has been boosted by the technological
development of analytical instrumentation generating a large volume of data. Such
information has increased in complexity from basic (i.e., blood samples) to
extensive sets encompassing many aspects of a subject phenotype, and now rapidly
extending into genetic and, more recently, radiomic information. Radiogenomics
integrates both aspects, investigating the relationship between imaging features
and gene expression. From a methodological point of view, radiogenomics takes
advantage of non-conventional data analysis techniques that reveal meaningful
information for decision-support in cancer diagnosis and treatment. This survey
is aimed to review the state-of-the-art techniques employed in radiomics and
genomics with special focus on analysis methods based on molecular and multimodal
probes. The impact of single and combined techniques will be discussed in light
of their suitability in correlation and predictive studies of specific oncologic
diseases.
PMID- 28417934
TI - Expression of Adenosine A2B Receptor and Adenosine Deaminase in Rabbit Gastric
Mucosa ECL Cells.
AB - Adenosine is readily available to the glandular epithelium of the stomach. Formed
continuously in intracellular and extracellular locations, it is notably produced
from ATP released in enteric cotransmission. Adenosine analogs modulate chloride
secretion in gastric glands and activate acid secretion in isolated parietal
cells through A2B adenosine receptor (A2BR) binding. A functional link between
surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but
whether this connection is a general feature of gastric mucosa cells is unknown.
Here we examine whether A2BR is expressed at the membrane of histamine-producing
enterochromaffin-like (ECL) cells, the major endocrine cell type in the oxyntic
mucosa, and if so, whether it has a vicinity relationship with ADA. We used a
highly homogeneous population of rabbit ECL cells (size 7.5-10 um) after
purification by elutriation centrifugation. The surface expression of A2BR and
ADA proteins was assessed by flow cytometry and confocal microscopy. Our findings
demonstrate that A2BR and ADA are partially coexpressed at the gastric ECL cell
surface and that A2BR is functional, with regard to binding of adenosine analogs
and adenylate cyclase activation. The physiological relevance of A2BR and ADA
association in regulating histamine release is yet to be explained.
PMID- 28417935
TI - Diagnostic Limitation of Fine-Needle Aspiration (FNA) on Indeterminate Thyroid
Nodules Can Be Partially Overcome by Preoperative Molecular Analysis: Assessment
of RET/PTC1 Rearrangement in BRAF and RAS Wild-Type Routine Air-Dried FNA
Specimens.
AB - Molecular markers are helpful diagnostic tools, particularly for cytologically
indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in
BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation
of an unambiguous surgical plan. Cycle threshold values according to the cell
count for detection of the RET/PTC1 rearrangement by real-time reverse
transcription-polymerase chain reaction (RT-PCR) using fresh and routine air
dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement
between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded
(FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and
RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the
Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used,
expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles,
respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE
papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty
nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1
rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and
the Nanostring showed moderate agreement with a kappa value of 0.56 (p = 0.002).
The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA
specimen was confirmed to be technically applicable. A significant proportion
(38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements.
PMID- 28417936
TI - Oncolytic Alphaviruses in Cancer Immunotherapy.
AB - Oncolytic viruses show specific targeting and killing of tumor cells and
therefore provide attractive assets for cancer immunotherapy. In parallel to
oncolytic viral vectors based on adenoviruses and herpes simplex viruses,
oncolytic RNA viruses and particularly alphaviruses have been evaluated as
delivery vehicles. Immunization studies in experimental rodent models for various
cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and
lung cancer as well as melanoma have been conducted with naturally occurring
oncolytic alphavirus strains such as M1 and Sindbis AR339. Moreover, animals were
vaccinated with engineered oncolytic replication-deficient and -competent Semliki
Forest virus, Sindbis virus and Venezuelan equine encephalitis virus vectors
expressing various antigens. Vaccinations elicited strong antibody responses and
resulted in tumor growth inhibition, tumor regression and even complete tumor
eradication. Vaccination also led to prolonged survival in several animal models.
Furthermore, preclinical evaluation demonstrated both prophylactic and
therapeutic efficacy of oncolytic alphavirus administration. Clinical trials in
humans have mainly been limited to safety studies so far.
PMID- 28417937
TI - Study on the Health Status and Health Service Utilization of the Elderly of a
Remote and Poor Village in a Mountainous Area in Jinzhai, Anhui.
AB - Background: Despite the rapid development of China's economy, a number of poor
areas in China continue to exist. The health status of the elderly in the poor
areas is a matter of concern. This study aims to explore the status of the
elderly in terms of their health status, health service needs, and utilization
among rural residents of a remote and poor village in a mountainous area in
Jinzhai, Anhui. Furthermore, this study aims to explore the differences between
the nation rural area average level and the remote and poor village in the
mountainous area in terms of health status and health service utilization.
Methods: Cluster sampling was used to obtain the sample. A total of 110 elderly
people were selected from the village, and face-to-face interviews were conducted
with questionnaires by trained investigators to collect data. Results: All items
except vision, language disability, and self-care disability were found to be
higher than the national average level. In terms of mental health, Zishu Village
has a ratio of 44.1% for the symptoms of anxiety and depression, which is higher
than the average for the national rural areas. The two-week prevalence rate,
prevalence of chronic diseases, and non-hospitalization rate of those who need
hospitalization (%) in Zishu Village was 62.7%, 88.2%, and 47.6% respectively,
which was higher than the rural values of the National Survey (2008). Most of the
outpatient visits were to the village clinics, while the hospitalizations were
mainly to county hospitals. The two-week visiting rate was 24.1%, which was lower
than 2008. The hospitalization rate in Zishu Village was 10.8%, which is similar
to the level of 2008. Conclusions: The health level and the utilization of health
services of the people in Zishu Village, Jinzhai, are generally lower than the
national average. Financial difficulties continue to remain the major factor
affecting the utilization of hospitalization services of this remote and poor
village in Jinzhai, Anhui.
PMID- 28417938
TI - Recent Advances in Cyanamide Chemistry: Synthesis and Applications.
AB - The application of alkyl and aryl substituted cyanamides in synthetic chemistry
has diversified multi-fold in recent years. In this review, we discuss recent
advances (since 2012) in the chemistry of cyanamides and detail their application
in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic
cyanide-transfer agents and their unique radical and coordination chemistry.
PMID- 28417939
TI - Soil Lead and Children's Blood Lead Disparities in Pre- and Post-Hurricane
Katrina New Orleans (USA).
AB - This study appraises New Orleans soil lead and children's lead exposure before
and ten years after Hurricane Katrina flooded the city. Introduction: Early
childhood exposure to lead is associated with lifelong and multiple health,
learning, and behavioral disorders. Lead exposure is an important factor
hindering the long-term resilience and sustainability of communities. Lead
exposure disproportionately affects low socioeconomic status of communities. No
safe lead exposure is known and the common intervention is not effective. An
essential responsibility of health practitioners is to develop an effective
primary intervention. Methods: Pre- and post-Hurricane soil lead and children's
blood lead data were matched by census tract communities. Soil lead and blood
lead data were described, mapped, blood lead graphed as a function of soil lead,
and Multi-Response Permutation Procedures statistics established disparities.
Results: Simultaneous decreases occurred in soil lead accompanied by an
especially large decline in children's blood lead 10 years after Hurricane
Katrina. Exposure disparities still exist between children living in the interior
and outer areas of the city. Conclusions: At the scale of a city, this study
demonstrates that decreasing soil lead effectively reduces children's blood lead.
Primary prevention of lead exposure can be accomplished by reducing soil lead in
the urban environment.
PMID- 28417940
TI - Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer
and Normal Cells, and Effects Cisplatin Cytotoxicity.
AB - Uncaria tomentosa is a woody vine with a long history of use in traditional
Peruvian medicine and nowadays supplements containing this vine as ingredient are
available. Immunomodulating, anti-inflammatory and anticancer properties of
Uncaria tomentosa have been suggested and attributed mainly to the presence of
tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of
different compounds occurring in extracts and modulation of redox processes may
significantly influence the anticancer activity of Uncaria tomentosa. The aim of
the present study was to investigate for the first time the cytotoxic effects of
the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria
tomentosa leaf blades in normal and cancer cells, and to assess the effect of the
tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract
was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2
cells. The extract increased ROS production in HepG2 cells, which resulted in
decreased GSH level, leading to apoptosis of these cells through activation of
caspase-3 and caspase-7. A reduction of NF-kappaB active form was observed in
cancer cells. In normal cells the extract did not affect ROS production, GSH
level and NF-kappaB activity, and maintained cell viability. HepG2 cells
incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted
in an increase in CDPP cytotoxic activity against HepG2, while under the same
conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP.
The results indicate that Uncaria tomentosa leaves decoction modulates
differently cancer and normal cells oxidative metabolism and, enhanced
cytotoxicity of CDDP against cancer cells and at the same time increased normal
healthy cells resistance to cisplatin. Further studies are needed to confirm our
observations and to describe underlying molecular mechanism, and the potential
usefulness of Uncaria tomentosa decoction in adjuvant therapy for cancer.
PMID- 28417941
TI - Mapping Patterns and Trends in the Spatial Availability of Alcohol Using Low
Level Geographic Data: A Case Study in England 2003-2013.
AB - Much literature examines the relationship between the spatial availability of
alcohol and alcohol-related harm. This study aims to address an important gap in
this evidence by using detailed outlet data to examine recent temporal trends in
the sociodemographic distribution of spatial availability for different types of
alcohol outlet in England. Descriptive analysis of measures of alcohol outlet
density and proximity using extremely high resolution market research data
stratified by outlet type and quintiles of area-level deprivation from 2003,
2007, 2010 and 2013 was undertaken and hierarchical linear growth models fitted
to explore the significance of socioeconomic differences. We find that overall
availability of alcohol changed very little from 2003 to 2013 (density +1.6%),
but this conceals conflicting trends by outlet type and area-level deprivation.
Mean on-trade density has decreased substantially (-2.2 outlets within 1 km
(Inter-Quartile Range (IQR) -3-0), although access to restaurants has increased
(+1.0 outlets (IQR 0-1)), while off-trade access has risen substantially (+2.4
outlets (IQR 0-3)). Availability is highest in the most deprived areas (p <
0.0001) although these areas have also seen the greatest falls in on-trade outlet
availability (p < 0.0001). This study underlines the importance of using
detailed, low-level geographic data to understand patterns and trends in the
spatial availability of alcohol. There are significant variations in these trends
by outlet type and deprivation level which may have important implications for
health inequalities and public health policy.
PMID- 28417943
TI - LC-ESI-MS/MS Identification of Biologically Active Phenolic Compounds in
Mistletoe Berry Extracts from Different Host Trees.
AB - A new, rapid, sensitive and selective liquid chromatography-electrospray
ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to
determine the content of flavonoid aglycones and phenolic acids in mistletoe
berries (Viscum album L.) harvested from six different Polish host trees.
Additionally, the total phenolic content (TPC) and total flavonoid content (TFC)
as well as an antioxidant and antiproliferative activity were evaluated for the
first time. The plant material was selectively extracted using ultrasound
assisted maceration with methanol/water (8:2) solution. The obtained TPC and TFC
results varied from 7.146 to 9.345 mg GA g-1 and from 1.888 to 2.888 mg Q g-1 of
dry extracts, respectively. The LC-ESI-MS/MS analysis demonstrated the highest
content of phenolic acids in mistletoe berries from Populus nigra 'Italica' L.
and flavonoid aglycones in mistletoe berries from Tilia cordata Mill. (354.45 ug
and 5.955 ug per g dry extract, respectively). The moderate antioxidant activity
of investigated extracts was obtained. The studies revealed that the examined
extracts decreased the proliferation of human colon adenocarcinoma cells line
LS180 in a dose-dependent manner without cytotoxicity in the human colon
epithelial cell line CCD 841 CoTr. Moreover, the obtained results suggest
considerable impact of polyphenols on the anticancer activity of these extracts.
PMID- 28417942
TI - Protein Discovery: Combined Transcriptomic and Proteomic Analyses of Venom from
the Endoparasitoid Cotesia chilonis (Hymenoptera: Braconidae).
AB - Many species of endoparasitoid wasps provide biological control services in
agroecosystems. Although there is a great deal of information on the ecology and
physiology of host/parasitoid interactions, relatively little is known about the
protein composition of venom and how specific venom proteins influence
physiological systems within host insects. This is a crucial gap in our knowledge
because venom proteins act in modulating host physiology in ways that favor
parasitoid development. Here, we identified 37 possible venom proteins from the
polydnavirus-carrying endoparasitoid Cotesia chilonis by combining transcriptomic
and proteomic analyses. The most abundant proteins were hydrolases, such as
proteases, peptidases, esterases, glycosyl hydrolase, and endonucleases. Some
components are classical parasitoid venom proteins with known functions,
including extracellular superoxide dismutase 3, serine protease inhibitor and
calreticulin. The venom contains novel proteins, not recorded from any other
parasitoid species, including tolloid-like proteins, chitooligosaccharidolytic
beta-N-acetylglucosaminidase, FK506-binding protein 14, corticotropin-releasing
factor-binding protein and vascular endothelial growth factor receptor 2. These
new data generate hypotheses and provide a platform for functional analysis of
venom components.
PMID- 28417944
TI - Variable Admittance Control Based on Fuzzy Reinforcement Learning for Minimally
Invasive Surgery Manipulator.
AB - In order to get natural and intuitive physical interaction in the pose adjustment
of the minimally invasive surgery manipulator, a hybrid variable admittance model
based on Fuzzy Sarsa(lambda)-learning is proposed in this paper. The proposed
model provides continuous variable virtual damping to the admittance controller
to respond to human intentions, and it effectively enhances the comfort level
during the task execution by modifying the generated virtual damping dynamically.
A fuzzy partition defined over the state space is used to capture the
characteristics of the operator in physical human-robot interaction. For the
purpose of maximizing the performance index in the long run, according to the
identification of the current state input, the virtual damping compensations are
determined by a trained strategy which can be learned through the experience
generated from interaction with humans, and the influence caused by humans and
the changing dynamics in the robot are also considered in the learning process.
To evaluate the performance of the proposed model, some comparative experiments
in joint space are conducted on our experimental minimally invasive surgical
manipulator.
PMID- 28417945
TI - One-Pot Phosphate-Mediated Synthesis of Novel 1,3,5-Trisubstituted Pyridinium
Salts: A New Family of S. aureus Inhibitors.
AB - Polysubstituted pyridinium salts are valuable pharmacophores found in many
biologically active molecules. Their synthesis typically involves the use of
multistep procedures or harsh reaction conditions. Here, we report water-based
phosphate mediated reaction conditions that promote the condensation of
arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction,
carried out at pH 6, provides conditions suitable for the use of less stable
aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of
selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit
the growth of S. aureus in the low MUg/mL range. The synthetic accessibility of
these compounds and preliminary growth inhibition data may pave the way towards
the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium
scaffold.
PMID- 28417946
TI - Essential Oils of Hyptis pectinata Chemotypes: Isolation, Binary Mixtures and
Acute Toxicity on Leaf-Cutting Ants.
AB - Leaf-cutting ants are pests of great economic importance due to the damage they
cause to agricultural and forest crops. The use of organosynthetic insecticides
is the main form of control of these insects. In order to develop safer
technology, the objective of this work was to evaluate the formicidal activity of
the essential oils of two Hyptis pectinata genotypes (chemotypes) and their major
compounds on the leaf-cutting ants Acromyrmex balzani Emery and Atta sexdens
rubropilosa Forel. Bioassays of exposure pathways (contact and fumigation) and
binary mixtures of the major compounds were performed. The major compounds
identified in the essential oils of H. pectinata were beta-caryophyllene,
caryophyllene oxide and calamusenone. The essential oils of H. pectinata were
toxic to the ants in both exposure pathways. Essential oils were more toxic than
their major compounds alone. The chemotype calamusenone was more toxic to A.
balzani in both exposure pathways. A. sexdens rubropilosa was more susceptible to
the essential oil of the chemotype beta-caryophyllene in both exposure pathways.
In general, the binary mixtures of the major compounds resulted in additive
effect of toxicity. The essential oils of H. pectinata is a raw material of great
potential for the development of new insecticides.
PMID- 28417947
TI - Pro-Angiogenic Effects of Low Dose Ethoxidine in a Murine Model of Ischemic
Hindlimb: Correlation between Ethoxidine Levels and Increased Activation of the
Nitric Oxide Pathway.
AB - Ethoxidine, a benzo[c]phenanthridine derivative, has been identified as a potent
inhibitor of topoisomerase I in cancer cell lines. Our group has reported
paradoxical properties of ethoxidine in cellular processes leading to
angiogenesis on endothelial cells. Because low concentration ethoxidine is able
to favor angiogenesis, the present study aimed to investigate the ability of 10-9
M ethoxidine to modulate neovascularization in a model of mouse hindlimb
ischemia. After inducing unilateral hindlimb ischemia, mice were treated for 21
days with glucose 5% or with ethoxidine, to reach plasma concentrations
equivalent to 10-9 M. Laser Doppler analysis showed that recovery of blood flow
was 1.5 fold higher in ethoxidine-treated mice in comparison with control mice.
Furthermore, CD31 staining and angiographic studies confirmed an increase of
vascular density in ethoxidine-treated mice. This ethoxidine-induced recovery was
associated with an increase of NO production through an enhancement of eNOS
phosphorylation on its activator site in skeletal muscle from ischemic hindlimb.
Moreover, real-time RT-PCR and western blots have highlighted that ethoxidine has
pro-angiogenic properties by inducing a significant enhancement in vegf
transcripts and VEGF expression, respectively. These findings suggest that
ethoxidine could contribute to favor neovascularization after an ischemic injury
by promoting the NO pathway and VEGF expression.
PMID- 28417949
TI - Implementation and Analysis of Real-Time Streaming Protocols.
AB - Communication media have become the primary way of interaction thanks to the
discovery and innovation of many new technologies. One of the most widely used
communication systems today is video streaming, which is constantly evolving.
Such communications are a good alternative to face-to-face meetings, and are
therefore very useful for coping with many problems caused by distance. However,
they suffer from different issues such as bandwidth limitation, network
congestion, energy efficiency, cost, reliability and connectivity. Hence, the
quality of service and the quality of experience are considered the two most
important issues for this type of communication. This work presents a complete
comparative study of two of the most used protocols of video streaming, Real Time
Streaming Protocol (RTSP) and the Web Real-Time Communication (WebRTC). In
addition, this paper proposes two new mobile applications that implement those
protocols in Android whose objective is to know how they are influenced by the
aspects that most affect the streaming quality of service, which are the
connection establishment time and the stream reception time. The new video
streaming applications are also compared with the most popular video streaming
applications for Android, and the experimental results of the analysis show that
the developed WebRTC implementation improves the performance of the most popular
video streaming applications with respect to the stream packet delay.
PMID- 28417950
TI - Differential Gender Effects in the Relationship between Perceived Immune
Functioning and Autistic Traits.
AB - Altered immune functioning has been demonstrated in individuals with autism
spectrum disorder (ASD). The current study explores the relationship between
perceived immune functioning and experiencing ASD traits in healthy young adults.
N = 410 students from Utrecht University completed a survey on immune functioning
and autistic traits. In addition to a 1-item perceived immune functioning rating,
the Immune Function Questionnaire (IFQ) was completed to assess perceived immune
functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) was
completed to examine variation in autistic traits, including the domains "social
insights and behavior", "difficulties with change", "communication", "phantasy
and imagination", and "detail orientation". The 1-item perceived immune
functioning score did not significantly correlate with the total AQ score.
However, a significant negative correlation was found between perceived immune
functioning and the AQ subscale "difficulties with change" (r = -0.119, p =
0.019). In women, 1-item perceived immune functioning correlated significantly
with the AQ subscales "difficulties with change" (r = -0.149, p = 0.029) and
"communication" (r = -0.145, p = 0.032). In men, none of the AQ subscales
significantly correlated with 1-item perceived immune functioning. In conclusion,
a modest relationship between perceived immune functioning and several autistic
traits was found.
PMID- 28417951
TI - Association of Motorcycle Use with Risk of Overweight in Taiwanese Urban Adults.
AB - Sedentary transport is known to adversely affect health. Few studies have focused
on motorcycle use. This study examines the association of motorcycle use with
overweight in urban adults in Taiwan. Cross-sectional data from 1069 Taiwanese
adults aged 20-64 years in three urban cities were collected in 2015. Data on
self-reported body mass index, time spent in motorcycle use, lifestyle behavioral
factors, and sociodemographic variables were obtained. Unadjusted and adjusted
logistic regression models were applied. In Model 1, adults who spent more time
using a motorcycle (third quartile, odds ratio (OR) = 1.17; fourth quartile, OR =
1.60) were more likely to be overweight compared with the first quartile. In
Model 2, after adjusting for the covariates, only the fourth quartile of
motorcycle use (OR = 1.50) was associated with a higher risk of overweight.
Higher time spent in motorcycle use is related to higher risk of being
overweight, even after adjustment for potential demographic and behavioral
confounders. Intervention and behavioral change strategies targeting motorcycle
use should be considered.
PMID- 28417948
TI - ErbB Family Signalling: A Paradigm for Oncogene Addiction and Personalized
Oncology.
AB - ErbB family members represent important biomarkers and drug targets for modern
precision therapy. They have gained considerable importance as paradigms for
oncoprotein addiction and personalized medicine. This review summarizes the
current understanding of ErbB proteins in cell signalling and cancer and
describes the molecular rationale of prominent cases of ErbB oncoprotein
addiction in different cancer types. In addition, we have highlighted
experimental technologies for the development of innovative cancer cell models
that accurately predicted clinical ErbB drug efficacies. In the future, such
cancer models might facilitate the identification and validation of
physiologically relevant novel forms of oncoprotein and non-oncoprotein addiction
or synthetic lethality. The identification of genotype-drug response
relationships will further advance personalized oncology and improve drug
efficacy in the clinic. Finally, we review the most important drugs targeting
ErbB family members that are under investigation in clinical trials or that made
their way already into clinical routine. Taken together, the functional
characterization of ErbB oncoproteins have significantly increased our knowledge
on predictive biomarkers, oncoprotein addiction and patient stratification and
treatment.
PMID- 28417952
TI - Investigating the molecular mechanism of positive and negative allosteric
modulators in the calcium-sensing receptor dimer.
AB - Allosteric modulators that are targeting the calcium-sensing receptor (CaSR) hold
great therapeutic potential, and elucidating the molecular basis for modulation
would thus benefit the development of novel therapeutics. In the present study,
we aimed at investigating the mechanism of allosteric modulation in CaSR by
testing dimers carrying mutations in the allosteric site of one or both of the
subunits. To ensure measurements on a well-defined dimer composition, we applied
a trans-activation system in which only the specific heterodimer of two loss-of
function mutants responded to agonist. Although one of these mutants was
potentiated by a positive allosteric modulator, we showed that receptor activity
was further potentiated in a trans-activation heterodimer containing a single
allosteric site, however only when the allosteric site was located in the subunit
responsible for G protein coupling. On the contrary, preventing activation in
both subunits was necessary for obtaining full inhibition by a negative
allosteric modulator. These findings correlate with the proposed activation
mechanism of the metabotropic glutamate receptors (mGluRs), in which only a
single transmembrane domain is activated at a time. CaSR and mGluRs belong to the
class C G protein-coupled receptors, and our findings thus suggest that the
activation mechanism is common to this subfamily.
PMID- 28417954
TI - Oxygen Vacancy-Tuned Physical Properties in Perovskite Thin Films with Multiple B
site Valance States.
AB - Controlling oxygen content in perovskite oxides with ABO3 structure is one of
most critical steps for tuning their functionality. Notably, there have been
tremendous efforts to understand the effect of changes in oxygen content on the
properties of perovskite thin films that are not composed of cations with
multiple valance states. Here, we study the effect of oxygen vacancies on
structural and electrical properties in epitaxial thin films of SrFeO3-delta
(SFO), where SFO is a compound with multiple valance states at the B site.
Various annealing treatments are used to produce different oxygen contents in the
films, which has resulted in significant structural changes in the fully strained
SFO films. The out-of-plane lattice parameter and tetragonality increase with
decreasing oxygen concentration, indicating the crystal structure is closely
related to the oxygen content. Importantly, variation of the oxygen content in
the films significantly affects the dielectric properties, leakage conduction
mechanisms, and the resistive hysteresis of the materials. These results
establish the relationship between oxygen content and structural and functional
properties for a range of multivalent transition metal oxides.
PMID- 28417953
TI - Recombinant Adeno-Associated Virus-mediated rescue of function in a mouse model
of Dopamine Transporter Deficiency Syndrome.
AB - Dopamine Transporter Deficiency Syndrome (DTDS) is a rare autosomal recessive
disorder caused by loss-of-function mutations in dopamine transporter (DAT) gene,
leading to severe neurological disabilities in children and adults. DAT-Knockout
(DAT-KO) mouse is currently the best animal model for this syndrome, displaying
functional hyperdopaminergia and neurodegenerative phenotype leading to premature
death in ~36% of the population. We used DAT-KO mouse as model for DTDS to
explore the potential utility of a novel combinatorial adeno-associated viral
(AAV) gene therapy by expressing DAT selectively in DA neurons and terminals,
resulting in the rescue of aberrant striatal DA dynamics, reversal of
characteristic phenotypic and behavioral abnormalities, and prevention of
premature death. These data indicate the efficacy of a new combinatorial gene
therapy aimed at rescuing DA function and related phenotype in a mouse model that
best approximates DAT deficiency found in DTDS.
PMID- 28417955
TI - Zero birefringence films of pullulan ester derivatives.
AB - High-performance films with almost zero-birefringence and zero-wavelength
dispersion were succeeded to prepare from pullulan esters derivatives (PLEs)
without any additives. Optical transmittance analysis, birefringence measurement
of PLE cast film and hot stretched films, and infrared dichroism analysis were
conducted to characterize optical properties of PLE films comparing with
cellulose triacetate which is commercially used as low-birefringence in optical
devices. The aims of this study, characterization of optical properties of
pullulan esters, can develop a deep understanding of the fundamental knowing and
applicability of polysaccharides. Accordingly, authors believe this paper will
open the gate for researches in the application of polysaccharides.
PMID- 28417956
TI - Establishment and characterization of an orthotopic patient-derived Group 3
medulloblastoma model for preclinical drug evaluation.
AB - Medulloblastomas comprise a heterogeneous group of tumours and can be subdivided
into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct
prognosis, biological behaviour and implications for targeted therapies. Few
experimental models exist of the aggressive and poorly characterized Group 3
tumours. In order to establish a reproducible transplantable Group 3
medulloblastoma model for preclinical therapeutic studies, we acquired a patient
derived tumour sphere culture and inoculated low-passage spheres into the
cerebellums of NOD-scid mice. Mice developed symptoms of brain tumours with a
latency of 17-18 weeks. Neurosphere cultures were re-established and serially
transplanted for 3 generations, with a negative correlation between tumour
latency and numbers of injected cells. Xenografts replicated the phenotype of the
primary tumour, including high degree of clustering in DNA methylation analysis,
high proliferation, expression of tumour markers, MYC amplification and elevated
MYC expression, and sensitivity to the MYC inhibitor JQ1. Xenografts maintained
maintained expression of tumour-derived VEGFA and stromal-derived COX-2. VEGFA,
COX-2 and c-Myc are highly expressed in Group 3 compared to other medulloblastoma
subgroups, suggesting that these molecules are relevant therapeutic targets in
Group 3 medulloblastoma.
PMID- 28417957
TI - Attractive force-driven superhardening of graphene membranes as a pin-point
breaking of continuum mechanics.
AB - Bending at the nanometre scale can substantially modify the mechanical, chemical
and electronic properties of graphene membranes. The subsequent response of
chemical bonds leads to deviations from plate idealisation in continuum
mechanics. However, those phenomena have thus far been investigated exclusively
by measuring the electronic properties of graphene deformed by compressing and
stretching with local-probe techniques. Here, we report that the interatomic
attractive forces applied on the convexly-curved graphene by the probe tip give
rise to a pin-point breaking of the plate idealisation in the continuum
mechanics, facilitating atomically-localised enhancements in its chemical
reactivity and mechanical strength. Thorough characterisations were conducted by
atomic force microscopy and force field spectroscopy on hollow nanotubes, rolled
up graphene, with different diameters. Their topmost parts supplied well-defined
curvatures of the convex graphene. We found that a significant enhancement in the
out-of-plane Young's modulus from 13 to 163 GPa, "superhardening", was realised
with the nonlinear transition of bond configurations. Our findings provide a
fundamental understanding of the relationships between the structure of atomistic
membranes and the dynamic behaviour of approaching exterior atoms or molecules
and their subsequent interplay with chemical and mechanical properties. Thus,
these results encourage the application of such membranes in functionally
controllable materials or devices.
PMID- 28417958
TI - Widespread patterns of sexually dimorphic gene expression in an avian
hypothalamic-pituitary-gonadal (HPG) axis.
AB - The hypothalamic-pituitary-gonadal (HPG) axis is a key biological system required
for reproduction and associated sexual behaviors to occur. In the avian
reproductive model of the rock dove (Columba livia), we characterized the
transcript community of each tissue of the HPG axis in both sexes, thereby
significantly expanding our mechanistic insight into HPG activity. We report
greater sex-biased differential expression in the pituitary as compared to the
hypothalamus, with multiple genes more highly expressed in the male pituitary
being related to secretory function, and multiple genes more highly expressed in
the female pituitary being related to reproduction, growth, and development. We
report tissue-specific and sex-biased expression in genes commonly investigated
when studying reproduction, highlighting the need for sex parity in future
studies. In addition, we uncover new targets of investigation in both sexes,
which could potentially change our understanding of HPG function.
PMID- 28417959
TI - Genome sequence of Plasmopara viticola and insight into the pathogenic mechanism.
AB - Plasmopara viticola causes downy mildew disease of grapevine which is one of the
most devastating diseases of viticulture worldwide. Here we report a 101.3 Mb
whole genome sequence of P. viticola isolate 'JL-7-2' obtained by a combination
of Illumina and PacBio sequencing technologies. The P. viticola genome contains
17,014 putative protein-coding genes and has ~26% repetitive sequences. A total
of 1,301 putative secreted proteins, including 100 putative RXLR effectors and 90
CRN effectors were identified in this genome. In the secretome, 261 potential
pathogenicity genes and 95 carbohydrate-active enzymes were predicted.
Transcriptional analysis revealed that most of the RXLR effectors, pathogenicity
genes and carbohydrate-active enzymes were significantly up-regulated during
infection. Comparative genomic analysis revealed that P. viticola evolved
independently from the Arabidopsis downy mildew pathogen Hyaloperonospora
arabidopsidis. The availability of the P. viticola genome provides a valuable
resource not only for comparative genomic analysis and evolutionary studies among
oomycetes, but also enhance our knowledge on the mechanism of interactions
between this biotrophic pathogen and its host.
PMID- 28417960
TI - Normally lethal amino acid substitutions suppress an ultramutator DNA Polymerase
delta variant.
AB - In yeast, the pol3-01,L612M double mutant allele, which causes defects in DNA
polymerase delta (Pol delta) proofreading (pol3-01) and nucleotide selectivity
(pol3-L612M), confers an "ultramutator" phenotype that rapidly drives extinction
of haploid and diploid MMR-proficient cells. Here, we investigate antimutator
mutations that encode amino acid substitutions in Pol delta that suppress this
lethal phenotype. We find that most of the antimutator mutations individually
suppress the pol3-01 and pol3-L612M mutator phenotypes. The locations of many of
the amino acid substitutions in Pol delta resemble those of previously identified
antimutator substitutions; however, two novel mutations encode substitutions
(R674G and Q697R) of amino acids in the fingers domain that coordinate the
incoming dNTP. These mutations are lethal without pol3-L612M and markedly change
the mutation spectra produced by the pol3-01,L612M mutator allele, suggesting
that they alter nucleotide selection to offset the pol3-L612M mutator phenotype.
Consistent with this hypothesis, mutations and drug treatments that perturb dNTP
pool levels disproportionately influence the viability of pol3-L612M,R674G and
pol3-L612M,Q697R cells. Taken together, our findings suggest that mutation rate
can evolve through genetic changes that alter the balance of dNTP binding and
dissociation from DNA polymerases.
PMID- 28417961
TI - High-Throughput Sequencing and Co-Expression Network Analysis of lncRNAs and
mRNAs in Early Brain Injury Following Experimental Subarachnoid Haemorrhage.
AB - Subarachnoid haemorrhage (SAH) is a fatal neurovascular disease following
cerebral aneurysm rupture with high morbidity and mortality rates. Long non
coding RNAs (lncRNAs) are a type of mammalian genome transcript, are abundantly
expressed in the brain and are involved in many nervous system diseases. However,
little is currently known regarding the influence of lncRNAs in early brain
injury (EBI) after SAH. This study analysed the expression profiles of lncRNAs
and mRNAs in SAH brain tissues of mice using high-throughput sequencing. The
results showed a remarkable difference in lncRNA and mRNA transcripts between SAH
and control brains. Approximately 617 lncRNA transcripts and 441 mRNA transcripts
were aberrantly expressed at 24 hours after SAH. Gene ontology (GO) enrichment
and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the
differentially expressed mRNAs were mostly involved in inflammation. Based on the
lncRNA/mRNA co-expression network, knockdown of fantom3_F730004F19 reduced the
mRNA and protein levels of CD14 and toll-like receptor 4 (TLR4) and attenuated
inflammation in BV-2 microglia cells. These results indicate that lncRNA
fantom3_F730004F19 may be associated with microglia induced inflammation via the
TLR signaling pathway in EBI following SAH. LncRNA represent a potential
therapeutic target for the prognosis, diagnosis, and treatment of SAH.
PMID- 28417962
TI - Multiple p-n junction subwavelength gratings for transmission-mode electro-optic
modulators.
AB - We propose a free-space electro-optic transmission modulator based on multiple p
n-junction semiconductor subwavelength gratings. The proposed device operates
with a high-Q guided-mode resonance undergoing electro-optic resonance shift due
to direct electrical control. Using rigorous electrical and optical modeling
methods, we theoretically demonstrate a modulation depth of 84%, on-state
efficiency 85%, and on-off extinction ratio of 19 dB at 1,550 nm wavelength under
electrical control signals within a favorably low bias voltage range from -4 V to
+1 V. This functionality operates in the transmission mode and sustainable in the
high-speed operation regime up to a 10-GHz-scale modulation bandwidth in
principle. The theoretical performance prediction is remarkably advantageous over
plasmonic tunable metasurfaces in the power-efficiency and absolute modulation
depth aspects. Therefore, further experimental study is of great interest for
creating practical-level metasurface components in various application areas.
PMID- 28417963
TI - Loop diuretics affect skeletal myoblast differentiation and exercise-induced
muscle hypertrophy.
AB - Muscle wasting or sarcopenia contributes to morbidity and mortality in patients
with cancer, renal failure, or heart failure, and in elderly individuals. Na+-K+
2Cl- cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle,
where it contributes to the generation of membrane ion currents and potential.
However, the physiologic function of NKCC1 in myogenesis is unclear. We
investigated this issue using the NKCC1 inhibitors bumetanide and furosemide,
which are commonly used loop diuretics. NKCC1 protein levels increased during
C2C12 murine skeletal myoblast differentiation, similarly to those of the
myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly
suppressed myoblast fusion into myotubes and the expression of myogenin and MHC.
Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse
skeletal muscles after 6 weeks' voluntary wheel running. Immunofluorescence
analyses of myofiber cross-sections revealed more large myofibers after exercise,
but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10
mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced
skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart
failure may be attributable to treatment with loop diuretics.
PMID- 28417964
TI - Light-Patterned Current Generation in a Droplet Bilayer Array.
AB - We have created a 4 * 4 droplet bilayer array comprising light-activatable
aqueous droplet bio-pixels. Aqueous droplets containing bacteriorhodopsin (bR), a
light-driven proton pump, were arranged on a common hydrogel surface in lipid
containing oil. A separate lipid bilayer formed at the interface between each
droplet and the hydrogel; each bilayer then incorporated bR. Electrodes in each
droplet simultaneously measured the light-driven proton-pumping activities of
each bio-pixel. The 4 * 4 array derived by this bottom-up synthetic biology
approach can detect grey-scale images and patterns of light moving across the
device, which are transduced as electrical current generated in each bio-pixel.
We propose that synthetic biological light-activatable arrays, produced with soft
materials, might be interfaced with living tissues to stimulate neuronal
pathways.
PMID- 28417965
TI - Distinct subtypes of Alzheimer's disease based on patterns of brain atrophy:
longitudinal trajectories and clinical applications.
AB - Atrophy patterns on MRI can reliably predict three neuropathological subtypes of
Alzheimer's disease (AD): typical, limbic-predominant, or hippocampal-sparing. A
method to enable their investigation in the clinical routine is still lacking. We
aimed to (1) validate the combined use of visual rating scales for identification
of AD subtypes; (2) characterise these subtypes at baseline and over two years;
and (3) investigate how atrophy patterns and non-memory cognitive domains
contribute to memory impairment. AD patients were classified as either typical AD
(n = 100), limbic-predominant (n = 33), or hippocampal-sparing (n = 35) by using
the Scheltens' scale for medial temporal lobe atrophy (MTA), the Koedam's scale
for posterior atrophy (PA), and the Pasquier's global cortical atrophy scale for
frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n =
30). 230 healthy controls were also included. There was great overlap among
subtypes in demographic, clinical, and cognitive variables. Memory performance
was more dependent on non-memory cognitive functions in hippocampal-sparing and
the no atrophy group. Hippocampal-sparing and the no atrophy group showed less
aggressive disease progression. Visual rating scales can be used to identify
distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating
scales may facilitate investigation of AD heterogeneity in clinical routine.
PMID- 28417966
TI - The ecdysis triggering hormone system is essential for successful moulting of a
major hemimetabolous pest insect, Schistocerca gregaria.
AB - Insects are enclosed in a rigid exoskeleton, providing protection from
desiccation and mechanical injury. To allow growth, this armour needs to be
replaced regularly in a process called moulting. Moulting entails the production
of a new exoskeleton and shedding of the old one and is induced by a pulse in
ecdysteroids, which activates a peptide-mediated signalling cascade. In
Holometabola, ecdysis triggering hormone (ETH) is the key factor in this cascade.
Very little functional information is available in Hemimetabola, which display a
different kind of development characterized by gradual changes. This paper
reports on the identification of the ETH precursor and the pharmacological and
functional characterisation of the ETH receptor in a hemimetabolous pest species,
the desert locust, Schistocerca gregaria. Activation of SchgrETHR by SchgrETH
results in an increase of both Ca2+ and cyclic AMP, suggesting that SchgrETHR
displays dual coupling properties in an in vitro cell-based assay. Using qRT-PCR,
an in-depth profiling study of SchgrETH and SchgrETHR transcripts was performed.
Silencing of SchgrETH and SchgrETHR resulted in lethality at the expected time of
ecdysis, thereby showing their crucial role in moulting.
PMID- 28417967
TI - Nomograms for predicting the prognostic value of serological tumor biomarkers in
colorectal cancer patients after radical resection.
AB - A wide range of serum tumor biomarkers, including CA19-9, CA242, CA72-4, CA50,
and CA125, has been studied in association with colorectal cancer (CRC). However,
few previous studies have comprehensively considered the above tumor biomarkers
to assess their clinical significance in predicting prognosis. Data from Fudan
University Shanghai Cancer Center (FUSCC) between January 1, 2007 and December
30, 2012 was retrospectively analyzed. Univariate and multivariate analyses were
performed to assess the association between prognostic factors and survival
outcomes. Nomograms were established based on multivariate Cox regression model
analysis for overall survival (OS) and disease free survival (DFS), and c-indexes
were 0.772 (95% CI: 0.724-0.820) and 0.715 (95% CI: 0.678-0.752), respectively.
Subgroup analyses according to CEA status (high/normal) suggested that CA724 was
the only independent prognostic factor for OS (P = 0.001) and DFS (P < 0.001) in
the CEA-high group, while, in the CEA-normal group, the only independent
prognostic factor for OS (P = 0.031) and DFS (P = 0.043) was CA50. CA50 and CA724
could supplement CEA in monitoring recurrence and metastasis. Accordingly,
nomograms based on CEA, CA50, CA724 and other clinical-pathological factors could
improve prognosis prediction for colorectal cancer patients.
PMID- 28417968
TI - Rational development of a protective P. vivax vaccine evaluated with transgenic
rodent parasite challenge models.
AB - Development of a protective and broadly-acting vaccine against the most widely
distributed human malaria parasite, Plasmodium vivax, will be a major step
towards malaria elimination. However, a P. vivax vaccine has remained elusive by
the scarcity of pre-clinical models to test protective efficacy and support
further clinical trials. In this study, we report the development of a highly
protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21,
able to provide 100% sterile protection against a stringent sporozoite challenge
in rodent models to malaria, where IgG2a antibodies were associated with
protection in absence of detectable PvCSP-specific T cell responses.
Additionally, we generated two novel transgenic rodent P. berghei parasite lines,
where the P. berghei csp gene coding sequence has been replaced with either full
length P. vivax VK210 or the allelic VK247 csp that additionally express GFP
Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63
and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit
high level cross-protection against parasites expressing either CSP allele, which
provide accessible and affordable models suitable to support the development of
P. vivax vaccines candidates. Rv21 is progressing to GMP production and has
entered a path towards clinical evaluation.
PMID- 28417969
TI - Massive introgression drives species radiation at the range limit of Anopheles
gambiae.
AB - Impacts of introgressive hybridisation may range from genomic erosion and species
collapse to rapid adaptation and speciation but opportunities to study these
dynamics are rare. We investigated the extent, causes and consequences of a
hybrid zone between Anopheles coluzzii and Anopheles gambiae in Guinea-Bissau,
where high hybridisation rates appear to be stable at least since the 1990s.
Anopheles gambiae was genetically partitioned into inland and coastal
subpopulations, separated by a central region dominated by A. coluzzii.
Surprisingly, whole genome sequencing revealed that the coastal region harbours a
hybrid form characterised by an A. gambiae-like sex chromosome and massive
introgression of A. coluzzii autosomal alleles. Local selection on chromosomal
inversions may play a role in this process, suggesting potential for
spatiotemporal stability of the coastal hybrid form and providing resilience
against introgression of medically-important loci and traits, found to be more
prevalent in inland A. gambiae.
PMID- 28417970
TI - Inorganic carbon physiology underpins macroalgal responses to elevated CO2.
AB - Beneficial effects of CO2 on photosynthetic organisms will be a key driver of
ecosystem change under ocean acidification. Predicting the responses of
macroalgal species to ocean acidification is complex, but we demonstrate that the
response of assemblages to elevated CO2 are correlated with inorganic carbon
physiology. We assessed abundance patterns and a proxy for CO2:HCO3- use
(delta13C values) of macroalgae along a gradient of CO2 at a volcanic seep, and
examined how shifts in species abundance at other Mediterranean seeps are related
to macroalgal inorganic carbon physiology. Five macroalgal species capable of
using both HCO3- and CO2 had greater CO2 use as concentrations increased. These
species (and one unable to use HCO3-) increased in abundance with elevated CO2
whereas obligate calcifying species, and non-calcareous macroalgae whose CO2 use
did not increase consistently with concentration, declined in abundance.
Physiological groupings provide a mechanistic understanding that will aid us in
determining which species will benefit from ocean acidification and why.
PMID- 28417971
TI - Greater cerebellar gray matter volume in car drivers: an exploratory voxel-based
morphometry study.
AB - Previous functional neuroimaging studies have identified multiple brain areas
associated with distinct aspects of car driving in simulated traffic
environments. Few studies, however, have examined brain morphology associated
with everyday car-driving experience in real traffic. Thus, the aim of the
current study was to identify gray matter volume differences between drivers and
non-drivers. We collected T1-weighted structural brain images from 73 healthy
young adults (36 drivers and 37 non-drivers). We performed a whole-brain voxel
based morphometry analysis to examine between-group differences in regional gray
matter volume. Compared with non-drivers, drivers showed significantly greater
gray matter volume in the left cerebellar hemisphere, which has been associated
with cognitive rather than motor functioning. In contrast, we found no brain
areas with significantly greater gray matter volume in non-drivers compared with
drivers. Our findings indicate that experience with everyday car driving in real
traffic is associated with greater gray matter volume in the left cerebellar
hemisphere. This brain area may be involved in abilities that are critical for
driving a car, but are not commonly or frequently used during other daily
activities.
PMID- 28417972
TI - The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for
patients with hepatocellular carcinoma: A meta-analysis.
AB - The lymphocyte-to-monocyte ratio (LMR) has been reported to predict clinical
outcomes in multiple malignancies. The aim of this study was to assess the
prognostic role of pretreatment LMR in hepatocellular carcinoma (HCC). A total of
seven studies comprising 2,738 patients were included in the meta-analysis.
Pooled results showed that elevated LMR was significantly associated with
increased overall survival (OS) (HR: 0.31, 95% CI: 0.20-0.47, p < 0.001), disease
free survival (DFS)/recurrence-free survival (RFS) (HR: 0.57, 95% CI: 0.49-0.67,
p < 0.001). The favorable prognostic impact of high LMR on OS was observed in all
subgroup with different sample size, type of publication, NOS score, and the cut
off value of LMR. In addition, low LMR was significantly correlated with TNM
stage and BCLC stage. We therefore conclude that elevated pretreatment LMR could
be a favorable prognostic factor for clinical outcomes in patients with HCC.
PMID- 28417973
TI - Excitability in the p53 network mediates robust signaling with tunable activation
thresholds in single cells.
AB - Cellular signaling systems precisely transmit information in the presence of
molecular noise while retaining flexibility to accommodate the needs of
individual cells. To understand design principles underlying such versatile
signaling, we analyzed the response of the tumor suppressor p53 to varying levels
of DNA damage in hundreds of individual cells and observed a switch between
distinct signaling modes characterized by isolated pulses and sustained
oscillations of p53 accumulation. Guided by dynamic systems theory we show that
this requires an excitable network structure comprising positive feedback and
provide experimental evidence for its molecular identity. The resulting data
driven model reproduced all features of measured signaling responses and is
sufficient to explain their heterogeneity in individual cells. We present
evidence that heterogeneity in the levels of the feedback regulator Wip1 sets
cell-specific thresholds for p53 activation, providing means to modulate its
response through interacting signaling pathways. Our results demonstrate how
excitable signaling networks can provide high specificity, sensitivity and
robustness while retaining unique possibilities to adjust their function to the
physiology of individual cells.
PMID- 28417974
TI - The E. coli molecular phenotype under different growth conditions.
AB - Modern systems biology requires extensive, carefully curated measurements of
cellular components in response to different environmental conditions. While high
throughput methods have made transcriptomics and proteomics datasets widely
accessible and relatively economical to generate, systematic measurements of both
mRNA and protein abundances under a wide range of different conditions are still
relatively rare. Here we present a detailed, genome-wide transcriptomics and
proteomics dataset of E. coli grown under 34 different conditions. Additionally,
we provide measurements of doubling times and in-vivo metabolic fluxes through
the central carbon metabolism. We manipulate concentrations of sodium and
magnesium in the growth media, and we consider four different carbon sources
glucose, gluconate, lactate, and glycerol. Moreover, samples are taken both in
exponential and stationary phase, and we include two extensive time-courses, with
multiple samples taken between 3 hours and 2 weeks. We find that exponential
phase samples systematically differ from stationary-phase samples, in particular
at the level of mRNA. Regulatory responses to different carbon sources or salt
stresses are more moderate, but we find numerous differentially expressed genes
for growth on gluconate and under salt and magnesium stress. Our data set
provides a rich resource for future computational modeling of E. coli gene
regulation, transcription, and translation.
PMID- 28417975
TI - Exciton emission of quasi-2D InGaN in GaN matrix grown by molecular beam epitaxy.
AB - We investigate the emission from confined excitons in the structure of a single
monolayer-thick quasi-two-dimensional (quasi-2D) InxGa1-xN layer inserted in GaN
matrix. This quasi-2D InGaN layer was successfully achieved by molecular beam
epitaxy (MBE), and an excellent in-plane uniformity in this layer was confirmed
by cathodoluminescence mapping study. The carrier dynamics have also been
investigated by time-resolved and excitation-power-dependent photoluminescence,
proving that the recombination occurs via confined excitons within the ultrathin
quasi-2D InGaN layer even at high temperature up to ~220 K due to the enhanced
exciton binding energy. This work indicates that such structure affords an
interesting opportunity for developing high-performance photonic devices.
PMID- 28417977
TI - Multicolour nanoscopy of fixed and living cells with a single STED beam and
hyperspectral detection.
AB - The extension of fluorescence nanoscopy to larger numbers of molecular species
concurrently visualized by distinct markers is of great importance for advanced
biological applications. To date, up to four markers had been distinguished in
STED experiments featuring comparatively elaborate imaging schemes and optical
setups, and exploiting various properties of the fluorophores. Here we present a
simple yet versatile STED design for multicolour imaging below the diffraction
limit. A hyperspectral detection arrangement (hyperSTED) collects the
fluorescence in four spectral channels, allowing the separation of four markers
with only one excitation wavelength and a single STED beam. Unmixing of the
different marker signals based on the simultaneous readout of all channels is
performed with a non-negative matrix factorization algorithm. We illustrate the
approach showing four-colour nanoscopy of fixed and living cellular samples.
PMID- 28417976
TI - Revealing inhibition difference between PFI-2 enantiomers against SETD7 by
molecular dynamics simulations, binding free energy calculations and unbinding
pathway analysis.
AB - SETD7 is associated with multiple diseases related signaling pathways. (R)-PFI-2
is the first SETD7 inhibitor with nanomolar inhibitory potency. The activity of
(R)-PFI-2 is about 500 times over that of (S)-PFI-2. Understanding the mechanism
behind this difference will be helpful to discovery and design of more potent
SETD7 inhibitors. A computational study combining molecular dynamics simulation,
binding free energy calculations, and residue interaction network (RIN) was
performed on the (S)-PFI-2/SETD7 and (R)-PFI-2/SETD7 complexes to explore the
molecular mechanism behind the different inhibition activity. The results from
Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation show (R)
PFI-2 has lower binding free energy. Residues H252, D256, L267, Y335, G336 and
H339 are responsible for the binding of SETD7 to the (R)-PFI-2. RIN analysis
indicates van der Waals interaction is critical for the binding of (R)-PFI-2. The
results from adaptive basing force (ABF) simulation confirm that the free energy
barrier of (R)-PFI-2 dissociating from the SETD7 is larger than that of (S)-PFI
2. (S)-PFI-2 and (R)-PFI-2 dissociate from the SETD7 binding site along different
reaction coordinate and have potential mean of force (PMF) depth. Our simulations
results will be useful to understand molecular mechanism of activity difference
between PFI-2 enantiomers against SETD7.
PMID- 28417978
TI - Efficient Heat Dissipation of Uncooled 400-Gbps (16*25-Gbps) Optical Transceiver
Employing Multimode VCSEL and PD Arrays.
AB - An effective heat dissipation of uncooled 400-Gbps (16*25-Gbps) form-factor
pluggable (CDFP) optical transceiver module employing chip-on-board multimode 25
Gbps vertical-surface-emitting-laser (VCSEL) and 25-Gbps photodiode (PD) arrays
mounted on a brass metal core embedded within a printed circuit board (PCB) is
proposed and demonstrated. This new scheme of the hollow PCB filling with
thermally-dissipated brass metal core was simulated and used for high temperature
and long term stability operation of the proposed 400-Gbps CDFP transceiver.
During one-hour testing, a red-shift of central wavelength by 0.4-nm
corresponding temperature increment of 6.7 degrees C was observed with the brass
core assisted cooler module. Such a temperature change was significantly lower
than that of 28.3 degrees C for the optical transceiver driven with conventional
circuit board. After 100-m distance transmission over a multimode fiber (OM4),
the 400-Gbps CDFP transceiver exhibited dispersion penalty of 2.6-dB, power
budget of ? 3-dB, link loss of ? 0.63-dB, mask margin of 20%, and bit error rate
(BER) of <10-12 with maintained stability more than one hour. The developed 400
Gbps CDFP transceiver module employing low-power consumption VCSEL and PD arrays,
effective coupling lens arrays, and well thermal-dissipation brass metal core is
suitable for use in the low-cost and high-performance data center applications.
PMID- 28417979
TI - Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade
reclassification in favorable-risk men during active surveillance.
AB - BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as
both a one-time and longitudinal measure in men on active surveillance (AS).
METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate
cancer with serial PSA, digital rectal examination (DRE), prostate magnetic
resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens
have also been routinely obtained. Men with multiple PCA3 measures obtained over
?3 years of monitoring were included. Utility of first PCA3 score (fPCA3),
subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of
Gleason grade reclassification (GR, Gleason score >6) during follow-up. RESULTS:
In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2
years (interquartile range (IQR) 1-3) and from fPCA3 to sPCA3 was 5 years (IQR 4
6). During median follow-up of 6 years (IQR 5-8), 28 men (11%) underwent GR. Men
with GR had higher median fPCA3 (48.0 vs 24.5, P=0.007) and sPCA3 (63.5 vs 36.0,
P=0.002) than those without GR, while longitudinal change in PCA3 did not differ
by GR status (log-normalized rate 0.07 vs 0.06, P=0.53). In a multivariable model
including age, risk classification and PSA density, fPCA3 remained significantly
associated with GR (log(fPCA3) odds ratio=1.77, P=0.04). CONCLUSIONS: PCA3 scores
obtained during AS were higher in men who underwent GR, but the rate of change in
PCA3 over time did not differ by GR status. PCA3 was a significant predictor of
GR in a multivariable model including conventional risk factors, suggesting that
PCA3 provides incremental prognostic information in the AS setting.
PMID- 28417980
TI - Is active surveillance a suitable option for African American men with prostate
cancer? A systemic literature review.
AB - BACKGROUND: Certain patients presenting with either low or very-low-risk prostate
cancer (PCa) can represent a therapeutic dilemma for physicians. The oncologic
outcomes of active surveillance (AS) for men with very-low-risk PCa are overall
excellent. However, there are concerns about AS related to the potential for
upgrading or upstaging. The African American (AA) population is under-represented
in studies evaluating AS outcomes and this is particularly important because of
the unique epidemiology of PCa in AA men. METHODS: A literature review through
the Medline database published from 1990 until August 2015 was performed to
identify studies reporting outcomes of the AA population with low-risk PCa that
underwent either AS or treatment. An additional search for studies on genetic
mechanisms involved in development of PCa in AA men was also performed. RESULTS:
Eleven studies on pathologic results of AA men who would qualify for AS were
identified and in eight of these studies AA race was found to be associated with
adverse pathological outcomes such as positive surgical margins, upgrading or
upstaging. The other three studies reported no significance in these parameters
with respect to race. Five more studies reported outcomes of AS in AA men with
different study end points. AA men were mainly found to have a higher rate of
disease reclassification subsequent to active treatment. The studies on genetic
mechanisms also identified different genetic alterations in the AA population.
CONCLUSIONS: AA men with clinically defined low-risk PCa may have either a higher
grade or volume of cancer that was not detected on routine evaluation. Therefore,
AS among such patients should be approached with caution. We recommend discussing
such risks with AA patients with an acknowledgement that existing favorable
outcomes noted in largely Caucasian populations may not be applicable to AA
patients. We propose a modified evaluation plan for AA patients that includes an
early confirmatory biopsy preceded by an magnetic resonance imaging to optimally
detect occult cancer foci.
PMID- 28417981
TI - Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake
among Hong Kong Chinese men.
AB - BACKGROUND: In vitro and in vivo studies suggested that polyphenol
epigallocatechin 3-gallate (EGCG) in tea may have anti-carcinogenic effect on
prostate cells, but this protective effect has less been examined in epidemiology
studies. We aimed to investigate the association between prostate cancer (PCA)
risk and habitual green tea intake among Chinese men in Hong Kong; meanwhile, the
relationship with EGCG was also explored. METHODS: We consecutively recruited 404
PCA cases and 395 controls from the same hospital who had complete data on
habitual tea consumption, including green, oolong, black and pu'er tea. We
reconstructed the level of EGCG intake according to a standard questionnaire and
the analytic values for EGCG extracted from the literature published by Lin et
al. in 2003. We calculated odds ratios (ORs) for tea consumption and EGCG intake
using unconditional multiple logistic regression, and examined their exposure-
response relationships with PCA risk. RESULTS: A total of 32 cases and 50
controls reported habitual green tea drinking, showing an adjusted OR of 0.60
(95% confidence interval (CI): 0.37, 0.98). A moderate excess risk was observed
among the habitual pu'er tea drinkers (OR=1.44, 95% CI: 1.02, 1.91). A
significantly lower intake of EGCG was observed among cases (54.4 mg) than the
controls (72.5 mg), which resulted in an inverse gradient of PCA risk with the
increasing intake of EGCG (test for trend, P=0.015). CONCLUSION: PCA risk among
Chinese men in Hong Kong was inversely associated with green tea consumption and
EGCG intake, but these results need to be replicated in larger studies.
PMID- 28417982
TI - Total and beverage-specific alcohol intake and the risk of aggressive prostate
cancer: a case-control study.
AB - BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its
association with aggressive prostate cancer (APC) is uncertain. Recent studies
have shown a modest increase in risk of APC associated with heavy alcohol intake
while association for beverage types remain inconsistent. METHODS: Using a case
control design and self-administered questionnaire, we examined the association
between APC (high grade and/or advanced stage) and frequency and quantity of
alcohol intake 2 years prior to enrolment. Furthermore, we delineated the
relationships for beverage-specific intakes of beer, red wine, white wine and
spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake
frequency of ?5 days per week was associated with increased risk compared with no
beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine
was protective at all frequencies of consumption compared with those with no wine
intake. For every 10 g per week ethanol intake from beer increase, the odds of
advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was
observed for red or white wine while a marginal dose-response relationship was
found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and
possibly spirits consumption is associated with increased risk while no dose
response relationship was found for red or white wine. Wine drinkers at all
frequencies have a decreased risk of APC compared with those who did not drink
wine.
PMID- 28417983
TI - An approach to and web-based tool for infectious disease outbreak intervention
analysis.
AB - Infectious diseases are a leading cause of death globally. Decisions surrounding
how to control an infectious disease outbreak currently rely on a subjective
process involving surveillance and expert opinion. However, there are many
situations where neither may be available. Modeling can fill gaps in the decision
making process by using available data to provide quantitative estimates of
outbreak trajectories. Effective reduction of the spread of infectious diseases
can be achieved through collaboration between the modeling community and public
health policy community. However, such collaboration is rare, resulting in a lack
of models that meet the needs of the public health community. Here we show a
Susceptible-Infectious-Recovered (SIR) model modified to include control measures
that allows parameter ranges, rather than parameter point estimates, and includes
a web user interface for broad adoption. We apply the model to three diseases,
measles, norovirus and influenza, to show the feasibility of its use and describe
a research agenda to further promote interactions between decision makers and the
modeling community.
PMID- 28417984
TI - An audience with Jay Bradner.
PMID- 28417985
TI - Viral infections: Targeting host kinases.
PMID- 28417986
TI - Trial watch: Trends in clinical trial design complexity.
PMID- 28417987
TI - Cancer: Identifying synergistic drug combinations.
PMID- 28417988
TI - Analgesia: Designing out opioid side effects.
PMID- 28417989
TI - Antibiotics: Reversing resistance.
PMID- 28417990
TI - G protein-coupled receptors: Novel probe for MRGPRX2.
PMID- 28417991
TI - Esophageal and Small Intestinal Mucosal Integrity in Eosinophilic Esophagitis and
Response to an Elemental Diet.
AB - OBJECTIVES: The esophageal mucosal integrity is impaired in eosinophilic
esophagitis (EoE) and it has been suggested that the duodenal permeability is
increased. The absence of food allergens may restore the integrity. The aims of
this study were to assess duodenal permeability in EoE and to evaluate the effect
of an elemental diet on the esophageal and duodenal integrity. METHODS: In this
prospective study 17 adult EoE patients and 8 healthy controls (HC) were
included. Esophageal biopsy specimens were sampled before and after 4 weeks of
elemental diet to measure eosinophil counts and gene expression of tight junction
and barrier integrity proteins. Esophageal and duodenal impedance were measured
by electrical tissue impedance spectroscopy and Ussing chambers were used to
measure transepithelial resistance (TER) and transepithelial molecule flux. Small
intestinal permeability was measured using a test, measuring lactulose/mannitol
(L/M) ratios. RESULTS: In EoE patients, the esophageal but not the duodenal
integrity was impaired, compared with HC. We observed no significant difference
between L/M ratios of HC and EoE patients. After diet, eosinophil counts
decreased significantly, which was paralleled by normalization of esophageal
impedance and transepithelial molecule flux. The esophageal TER improved
significantly, but did not reach values seen in HC. Esophageal expression of
genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was
impaired at baseline and restored after diet. CONCLUSIONS: An elemental diet
restores esophageal integrity, suggesting that it is at least partly secondary to
allergen exposure. Duodenal integrity seems not to be affected in EoE, and
possibly plays a minor role in its pathophysiology.
PMID- 28417992
TI - Eluxadoline Efficacy in IBS-D Patients Who Report Prior Loperamide Use.
AB - OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is often managed with
over-the-counter therapies such as loperamide, though with limited success. This
analysis evaluated the efficacy of eluxadoline in patients previously treated
with loperamide in two phase 3 studies. METHODS: Adults with IBS-D (Rome III
criteria) were enrolled and randomized to placebo or eluxadoline (75 or 100 mg)
twice daily for 26 (IBS-3002) or 52 (IBS-3001) weeks. Patients reported
loperamide use over the previous year and recorded their rescue loperamide use
during the studies. The primary efficacy end point was the proportion of patients
with a composite response of simultaneous improvement in abdominal pain and
reduction in diarrhea. RESULTS: A total of 2,428 patients were enrolled; 36.0%
reported prior loperamide use, of whom 61.8% reported prior inadequate IBS-D
symptom control with loperamide. Among patients with prior loperamide use, a
greater proportion treated with eluxadoline (75 and 100 mg) were composite
responders vs. those treated with placebo with inadequate prior symptom control,
over weeks 1-12 (26.3% (P=0.001) and 27.0% (P<0.001) vs. 12.7%, respectively);
similar results were observed over weeks 1-26. When daily rescue loperamide use
was imputed as a nonresponse day, the composite responder rate was still higher
in patients receiving eluxadoline (75 and 100 mg) vs. placebo over weeks 1-12
(P<0.001) and weeks 1-26 (P<0.001). Adverse events included nausea and abdominal
pain. CONCLUSIONS: Eluxadoline effectively and safely treats IBS-D symptoms of
abdominal pain and diarrhea in patients who self-report either adequate or
inadequate control of their symptoms with prior loperamide treatment, with
comparable efficacy and safety irrespective of the use of loperamide as a rescue
medication during eluxadoline treatment.
PMID- 28417993
TI - Corrigendum: Responsiveness of Endoscopic Indices of Disease Activity for Crohn's
Disease.
PMID- 28417996
TI - Addendum.
PMID- 28417994
TI - Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada:
Distributed Network Analysis of Multiple Population-Based Provincial Health
Administrative Databases.
AB - OBJECTIVES: The incidence of pediatric-onset inflammatory bowel disease (IBD) is
increasing worldwide. We used population-based health administrative data to
determine national Canadian IBD incidence, prevalence, and trends over time of
childhood-onset IBD. METHODS: We identified children <16 years (y) diagnosed with
IBD 1999-2010 from health administrative data in five provinces (Alberta,
Manitoba, Nova Scotia, Ontario, Quebec), comprising 79.2% of the Canadian
population. Standardized incidence and prevalence were calculated per 100,000
children. Annual percentage change (APC) in incidence and prevalence were
determined using Poisson regression analysis. Provincial estimates were meta
analyzed using random-effects models to produce national estimates. RESULTS:
5,214 incident cases were diagnosed during the study period (3,462 Crohn's
disease, 1,382 ulcerative colitis, 279 type unclassifiable). The incidence in
Canada was 9.68 (95% CI 9.11 to 10.25) per 100,000 children. Incidence was
similar amongst most provinces, but higher in Nova Scotia. APC in incidence did
not significantly change over the study period in the overall cohort (+2.06%, 95%
CI -0.64% to +4.76%). However, incidence significantly increased in children aged
0-5y (+7.19%, 95% +2.82% to +11.56%). Prevalence at the end of the study period
in Canada was 38.25 (95% CI 35.78 to 40.73) per 100,000 children. Prevalence
increased significantly over time, APC +4.56% (95% CI +3.71% to +5.42%).
CONCLUSIONS: Canada has amongst the highest incidence of childhood-onset IBD in
the world. Prevalence significantly increased over time. Incidence was not
statistically changed with the exception of a rapid increase in incidence in the
youngest group of children.
PMID- 28417995
TI - Corrigendum: Do Primary Care Provider Strategies Improve Patient Participation in
Colorectal Cancer Screening?
AB - This corrects the article DOI: 10.1038/ajg.2017.4.
PMID- 28417997
TI - Iterative expansion microscopy.
AB - We recently developed a method called expansion microscopy, in which preserved
biological specimens are physically magnified by embedding them in a densely
crosslinked polyelectrolyte gel, anchoring key labels or biomolecules to the gel,
mechanically homogenizing the specimen, and then swelling the gel-specimen
composite by ~4.5* in linear dimension. Here we describe iterative expansion
microscopy (iExM), in which a sample is expanded ~20*. After preliminary
expansion a second swellable polymer mesh is formed in the space newly opened up
by the first expansion, and the sample is expanded again. iExM expands biological
specimens ~4.5 * 4.5, or ~20*, and enables ~25-nm-resolution imaging of cells and
tissues on conventional microscopes. We used iExM to visualize synaptic proteins,
as well as the detailed architecture of dendritic spines, in mouse brain
circuitry.
PMID- 28417998
TI - Marker-free coselection for CRISPR-driven genome editing in human cells.
AB - Targeted genome editing enables the creation of bona fide cellular models for
biological research and may be applied to human cell-based therapies. Therefore,
broadly applicable and versatile methods for increasing its efficacy in cell
populations are highly desirable. We designed a simple and robust coselection
strategy for enrichment of cells with either nuclease-driven nonhomologous end
joining (NHEJ) or homology-directed repair (HDR) events by harnessing the
multiplexing capabilities of CRISPR-Cas9 and Cpf1 systems. Selection for dominant
alleles of the ubiquitous sodium/potassium pump (Na+/K+ ATPase) that rendered
cells resistant to ouabain was used to enrich for custom genetic modifications at
another unlinked locus of interest, thereby effectively increasing the recovery
of engineered cells. The process is readily adaptable to transformed and primary
cells, including hematopoietic stem and progenitor cells. The use of universal
CRISPR reagents and a commercially available small-molecule inhibitor streamlines
the incorporation of marker-free genetic changes in human cells.
PMID- 28418000
TI - SCnorm: robust normalization of single-cell RNA-seq data.
AB - The normalization of RNA-seq data is essential for accurate downstream inference,
but the assumptions upon which most normalization methods are based are not
applicable in the single-cell setting. Consequently, applying existing
normalization methods to single-cell RNA-seq data introduces artifacts that bias
downstream analyses. To address this, we introduce SCnorm for accurate and
efficient normalization of single-cell RNA-seq data.
PMID- 28418001
TI - Effects of calcination temperature for rate capability of triple-shelled ZnFe2O4
hollow microspheres for lithium ion battery anodes.
AB - Triple-shelled ZnFe2O4 hollow microspheres (ZFO) as anode materials for lithium
ion battery are prepared through a one-pot hydrothermal reaction using the
composite solution consisting of sucrose in water and metal ions in ethylene
glycol (EG), followed by different calcination processes. The architectures of
ZFO micro spheres are differently synthesized through a mutual cooperation of
inward and outward ripening with three different calcination temperatures. Thin
triple-shelled ZnFe2O4 hollow microspheres calcined at 450 degrees C (ZFO-450)
delivers a high reversible capacity of 932 mA h g-1 at a current density of 2 A g
1 even at the 200th cycle without obvious decay. Furthermore, ZFO-450 delivers
1235, 1005, 865, 834, and 845 mA h g-1 at high current densities of 0.5, 2, 5,
10, and 20 A g-1 after 100 cycles. Thin triple-shelled hollow microsphere
prepared at an optimum calcination temperature provides exceptional rate
capability and outstanding rate retention due to (i) the formation of
nanoparticles leading to thin shell with morphological integrity, (ii) the facile
mass transfer by thin shell with mesoporous structure, and (iii) the void space
with macroporous structure alleviating volume change occurring during cycling.
PMID- 28417999
TI - A tiling-deletion-based genetic screen for cis-regulatory element identification
in mammalian cells.
AB - Millions of cis-regulatory elements are predicted to be present in the human
genome, but direct evidence for their biological function is scarce. Here we
report a high-throughput method, cis-regulatory element scan by tiling-deletion
and sequencing (CREST-seq), for the unbiased discovery and functional assessment
of cis-regulatory sequences in the genome. We used it to interrogate the 2-Mb
POU5F1 locus in human embryonic stem cells, and identified 45 cis-regulatory
elements. A majority of these elements have active chromatin marks, DNase
hypersensitivity, and occupancy by multiple transcription factors, which confirms
the utility of chromatin signatures in cis-element mapping. Notably, 17 of them
are previously annotated promoters of functionally unrelated genes, and like
typical enhancers, they form extensive spatial contacts with the POU5F1 promoter.
These results point to the commonality of enhancer-like promoters in the human
genome.
PMID- 28418002
TI - Immune Tissue Print and Immune Capture-PCR for Diagnosis and Detection of
Candidatus Liberibacter Asiaticus.
AB - 'Candidatus Liberibacter asiaticus' (CaLas), associated with citrus Huanglongbing
(HLB), is a non culturable member of the alpha-proteobacteria. In this study
serologically based methods for the detection of CaLas were developed. An anti
outer membrane protein A (OmpA) polyclonal antibody previously produced (in our
laboratory) was highly effective for the detection of CaLas from citrus tissues
in a simple tissue printing format. The antibody was also used to capture
bacteria from periwinkle extracts. About 80% of all field samples analyzed tested
positive with both immune tissue printing and qPCR; whereas 95% were positive
with at least one of these two methods. When asymptomatic citrus tissues were
tested, the tissue printing method gave a higher rate of detection (83%) than the
qPCR method (64%). This is consistent with a lower concentration of CaLas DNA,
but a higher proportion of viable cells, in the asymptomatic tissues. The immune
tissue printing method also highlights the detail of the spatial distribution of
'Ca. Liberibacter asiaticus' in diseased citrus tissues. Both the immune capture
PCR and immune tissue printing methods offer the advantages of low cost, high
throughput, ease of scaling for multiple samples and simplicity over current PCR
based methods for the detection of 'Ca. Liberibacter asiaticus'.
PMID- 28418003
TI - Toll-like receptor polymorphisms compromise the inflammatory response against
bacterial antigen translocation in cirrhosis.
AB - Bacterial translocation is associated with clinically relevant complications in
cirrhosis. We evaluated the effect of toll-like receptor polymorphisms in the
soluble response against these episodes. Consecutive patients with cirrhosis and
ascitic fluid were distributed by TLR2 rs4696480, TLR4 rs4986790, and TLR9
rs187084 single-nucleotide polymorphisms. Lipoteichoic acid, lipopolyssaccharide,
bacterial-DNA, pro-inflammatory cytokines and nitric oxide levels were quantified
in serum samples. In vitro response against specific ligands in variant TLR
genotypes was evaluated. One hundred and fourteen patients were included. Variant
TLR-2, TLR-4 and TLR-9 SNP genotypes were associated with significantly increased
serum levels of LTA, LPS and bacterial-DNA. TNF-alpha, IL-6 and nitric oxide
serum levels were significantly decreased in all variant TLR genotyped patients.
Cytokine levels were significantly less upregulated in response to specific TLR
ligands in patients with all variant vs wildtype TLR genotypes. Although in vitro
gene expression levels of all wildtype and variant TLRs were similar, MyD88 and
NFkB were significantly downregulated in cells from TLR-variant genotyped
patients in response to their ligands. Variant TLR genotypes are associated with
an increased circulating antigen burden and a decreased proinflammatory response
in cirrhosis. This immunodeficiency may facilitate bacteria-related complications
in cirrhosis and enhance TLR targeting for its management.
PMID- 28418005
TI - Simulated climate effects of desert irrigation geoengineering.
AB - Geoengineering, the deliberate large-scale manipulation of earth's energy balance
to counteract global warming, is an attractive proposition for sparsely populated
deserts. We use the BNU and UVic Earth system models to simulate the effects of
irrigating deserts under the RCP8.5 scenario. Previous studies focused on
increasing desert albedo to reduce global warming; in contrast we examine how
extending afforestation and ecological projects, that successfully improve
regional environments, fair for geoengineering purposes. As expected desert
irrigation allows vegetation to grow, with bare soil or grass gradually becoming
shrub or tree covered, with increases in terrestrial carbon storage of 90.3 Pg C
(UVic-ESCM) - 143.9 Pg C (BNU-ESM). Irrigating global deserts makes the land
surface temperature decrease by 0.48 degrees C and land precipitation increase
by 100 mm yr-1. In the irrigated areas, BNU-ESM simulates significant cooling of
up to 4.2 degrees C owing to the increases in low cloud and latent heat which
counteract the warming effect due to decreased surface albedo. Large volumes of
water would be required to maintain global desert irrigation, equivalent 10
mm/year of global sea level (BNU-ESM) compensate for evapotranspiration losses.
Differences in climate responses between the deserts prompt research into
tailored albedo-irrigation schemes.
PMID- 28418004
TI - Host Determinants of Expression of the Helicobacter pylori BabA Adhesin.
AB - Expression of the Helicobacter pylori blood group antigen binding adhesin A
(BabA) is more common in strains isolated from patients with peptic ulcer disease
or gastric cancer, rather than asymptomatic colonization. Here we used mouse
models to examine host determinants that affect H. pylori BabA expression. BabA
expression was lost by phase variation as frequently in WT mice as in RAG2-/-
mice that do not have functional B or T cells, and in MyD88-/-, TLR2-/- and TLR4
/- mice that are defective in toll like receptor signaling. The presence of other
bacteria had no effect on BabA expression as shown by infection of germ free
mice. Moreover, loss of BabA expression was not dependent on Leb expression or
the capacity of BabA to bind Leb. Surprisingly, gender was the host determinant
most associated with loss of BabA expression, which was maintained to a greater
extent in male mice and was associated with greater bacterial load. These results
suggest the possibility that loss of BabA expression is not driven by adaptive
immunity or toll-like receptor signaling, and that BabA may have other,
unrecognized functions in addition to serving as an adhesin that binds Leb.
PMID- 28418006
TI - Radiomics-based Prognosis Analysis for Non-Small Cell Lung Cancer.
AB - Radiomics characterizes tumor phenotypes by extracting large numbers of
quantitative features from radiological images. Radiomic features have been shown
to provide prognostic value in predicting clinical outcomes in several studies.
However, several challenges including feature redundancy, unbalanced data, and
small sample sizes have led to relatively low predictive accuracy. In this study,
we explore different strategies for overcoming these challenges and improving
predictive performance of radiomics-based prognosis for non-small cell lung
cancer (NSCLC). CT images of 112 patients (mean age 75 years) with NSCLC who
underwent stereotactic body radiotherapy were used to predict recurrence, death,
and recurrence-free survival using a comprehensive radiomics analysis. Different
feature selection and predictive modeling techniques were used to determine the
optimal configuration of prognosis analysis. To address feature redundancy,
comprehensive analysis indicated that Random Forest models and Principal
Component Analysis were optimum predictive modeling and feature selection
methods, respectively, for achieving high prognosis performance. To address
unbalanced data, Synthetic Minority Over-sampling technique was found to
significantly increase predictive accuracy. A full analysis of variance showed
that data endpoints, feature selection techniques, and classifiers were
significant factors in affecting predictive accuracy, suggesting that these
factors must be investigated when building radiomics-based predictive models for
cancer prognosis.
PMID- 28418007
TI - Saturated fatty acids induce development of both metabolic syndrome and
osteoarthritis in rats.
AB - The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA,
C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid
(SA, C18:0). The aim of this study was to investigate whether diets containing
individual SFA together with excess simple carbohydrates induce osteoarthritis
(OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats
were given either a corn starch diet or a diet composed of simple carbohydrates
together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef
tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also
exhibited cartilage degradation and subchondral bone changes similar to OA. In
contrast, replacement of beef tallow with LA decreased signs of metabolic
syndrome together with decreased cartilage degradation. Furthermore, PA and SA
but not LA increased release of matrix sulphated proteoglycans in cultures of
bovine cartilage explants or human chondrocytes. In conclusion, we have shown
that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like
knee changes. Thus, diets containing SFA are strongly relevant to the development
or prevention of both OA and metabolic syndrome.
PMID- 28418008
TI - Quantitative analyses of the global proteome and phosphoproteome reveal the
different impacts of propofol and dexmedetomidine on HT22 cells.
AB - Propofol and dexmedetomidine are both commonly used anaesthetics. Although they
employ two different mechanisms to induce anaesthesia, both compounds influence
the hippocampus and the HT22 cell line. HT22 cells are broadly used in
neurobiological research. In this study, we assessed the effects of propofol and
dexmedetomidine on signalling in HT22 cells. Using the SILAC (stable isotope
labelling with amino acids in cell culture) labelling technique, IMAC
(immobilized metal affinity chromatography) enrichment and high-resolution LC
MS/MS (liquid chromatography tandem mass spectrometry) analysis, we investigated
the quantitative proteome and phosphoproteome in HT22 cells treated with propofol
or dexmedetomidine. In total, 4,527 proteins and 6,824 phosphosites were
quantified in cells treated with these two anaesthetics. With the assistance of
intensive bioinformatics, the propofol and dexmedetomidine treatments were shown
to induce distinct proteome and phosphoproteome profiles in HT22 cells.
Consistent with our bioinformatics analysis, dexmedetomidine had a smaller effect
than propofol on cell survival. These findings deepen our understanding of drug
induced anaesthesia.
PMID- 28418009
TI - Effect of UMOD genotype on long-term graft survival after kidney transplantation
in patients treated with cyclosporine-based therapy.
AB - The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with
renal function, chronic kidney disease and hypertension with the minor T-allele
showing a protective effect. Hypertension and nephrotoxicity are adverse effects
of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor
kidneys associates with long-term graft survival in 393 Caucasian patients with
stable graft function for more than 10 weeks after kidney transplantation treated
with a cyclosporine-based maintenance therapy (mean graft survival 9 years).
Presence of the donor T-allele had no effect on blood pressure, serum creatinine
1 year after transplantation, and on number of acute graft rejections during the
first year. No significant effect on overall graft survival was observed in
Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis,
presence of donor T-allele associated with a significant lower hazard ratio of
0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective
effect of the donor T-allele on graft loss observed in multivariate adjusted
analysis justifies further investigations including patients treated with similar
or other immunosuppressive regimens.
PMID- 28418010
TI - Interaction between NUDT15 and ABCC4 variants enhances intolerability of 6
mercaptopurine in Japanese patients with childhood acute lymphoblastic leukemia.
AB - 6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic
leukemia (ALL) treatment. Some candidate gene variants are associated with its
toxicities, but the major variants and effects of combined variants remain
unclear. We used Cox regression analysis to evaluate the time-dependent
association between candidate variants and the cumulative incidence of 6-MP
intolerability in 95 Japanese patients. The major risk factors for severe
leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi
covariate analysis (P<0.05). NUDT15 intermediate activity variant, that is,
heterozygous rs116855232 or rs186364861 variant, and the ABCC4 rs3765534 variant
showed leukopenia more frequently than either variant alone. All patients with
both the intermediate activity NUDT15 variant and the ABCC4 rs3765534 variant
suffered from leukopenia, and 57.1% patients required 50% protocol dose by day
168. These data indicate that NUDT15 and ABCC4 are major factors for 6-MP
intolerability and that the interaction between these variants enhances
intolerability to 6-MP.
PMID- 28418011
TI - More than 25 years of genetic studies of clozapine-induced agranulocytosis.
AB - Clozapine is one of the most effective atypical antipsychotic drugs prescribed to
patients with treatment-resistant schizophrenia. Approximately 1% of patients
experience potential life-threatening adverse effects in the form of
agranulocytosis, greatly hindering its applicability in clinical practice. The
etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is
thought to be a heritable trait. We reviewed the genetic studies of CIA published
thus far. One recurrent finding from early candidate gene study to more recent
genome-wide analysis is that of the involvement of human leukocyte antigen locus.
We conclude that CIA is most likely a complex, polygenic trait, which may hamper
efforts to the development of a genetic predictor test with clinical relevance.
To decipher the genetic architecture of CIA, it is necessary to apply more
rigorous standards of phenotyping and study much larger sample sizes.
PMID- 28418013
TI - A graphene based frequency quadrupler.
AB - Benefit from exceptional electrical transport properties, graphene receives
worldwide attentions, especially in the domain of high frequency electronics. Due
to absence of effective bandgap causing off-state the device, graphene material
is extraordinarily suitable for analog circuits rather than digital applications.
With this unique ambipolar behavior, graphene can be exploited and utilized to
achieve high performance for frequency multipliers. Here, dual-gated graphene
field-effect transistors have been firstly used to achieve frequency quadrupling.
Two Dirac points in the transfer curves of the designed GFETs can be observed by
tuning top-gate voltages, which is essential to generate the fourth harmonic. By
applying 200 kHz sinusoid input, arround 50% of the output signal radio frequency
power is concentrated at the desired frequency of 800 kHz. Additionally, in
suitable operation areas, our devices can work as high performance frequency
doublers and frequency triplers. Considered both simple device structure and
potential superhigh carrier mobility of graphene material, graphene-based
frequency quadruplers may have lots of superiorities in regards to ultrahigh
frequency electronic applications in near future. Moreover, versatility of carbon
material system is far-reaching for realization of complementary metal-oxide
semiconductor compatible electrically active devices.
PMID- 28418012
TI - CYP3A4 is a crosslink between vitamin D and calcineurin inhibitors in solid organ
transplant recipients: implications for bone health.
AB - The use of calcineurin inhibitors (CNIs) and vitamin D deficiency may contribute
to the pathogenesis of post-transplant bone disease. CNIs and 1,25
dihydroxyvitamin D3 (1,25(OH)2D3) are substrates of the drug-metabolizing enzyme
CYP3A4. This review summarizes the indications for the use of activated vitamin D
analogs in post-transplant care and the current knowledge on the impact of CNIs
on bone. We searched for clinical evidence of the interaction between CNIs and
1,25(OH)2D3. We also provide an overview of the literature on the interplay
between vitamin D metabolism and CYP3A4 in experimental and clinical settings and
discuss its possible implications for solid organ transplant recipients. In
conclusion, there is a body of evidence on the interplay between vitamin D and
the drug-metabolizing enzyme CYP3A4, which may have therapeutic implications.
PMID- 28418014
TI - The relationship between allergic status and adenotonsillar regrowth: a
retrospective research on children after adenotonsillectomy.
AB - Adenotonsillar regrowth in children after adenotonsillectomy (T&A) for
obstructive sleep apnea (OSA) is often seen in clinical treatment, however, the
relationship between allergic disease and adenotonsillar regrowth remains
unclear. In this retrospective study, children were assigned to either the
recurrence or control group, and subdivided by age at operation. Among children
over 36 months, those in the recurrence group had more allergic disease and
higher IgE, IL-4, and IL-5 levels than the same-aged children in control group.
The Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores for
nasal symptoms and activity were higher in children older than 36 months in
recurrence group. The results of immunohistochemistry and immunofluorescence
showed that FoxP3+ cells (Tregs) were less, while GATA3+ cells (Th2 cells) were
more in recurrence group for all ages. Allergic status and low levels of FoxP3
were proved as independent risk factors for adenotonsillar regrowth by
multivariate logistic regression. These results indicate that allergic disease is
a risk factor for adenotonsillar regrowth in children following T&A for OSA, and
this risk increases with age. The decreased level of Tregs and subsequent changes
in immune function play an important role in the pathogenesis of adenotonsillar
regrowth.
PMID- 28418015
TI - Diabetes: LMPTP inhibitors - potential treatment for type 2 diabetes?
PMID- 28418016
TI - Pituitary function: Pulsatile GnRH therapy in CCPHD.
PMID- 28418017
TI - Accessing Forbidden Glass Regimes through High-Pressure Sub-Tg Annealing.
AB - Density and hardness of glasses are known to increase upon both compression at
the glass transition temperature (Tg) and ambient pressure sub-Tg annealing.
However, a serial combination of the two methods does not result in higher
density and hardness, since the effect of compression is countered by subsequent
annealing and vice versa. In this study, we circumvent this by introducing a
novel treatment protocol that enables the preparation of high-density, high
hardness bulk aluminosilicate glasses. This is done by first compressing a sodium
magnesium aluminosilicate glass at 1 GPa at Tg, followed by sub-Tg annealing in
situ at 1 GPa. Through density, hardness, and heat capacity measurements, we
demonstrate that the effects of hot compression and sub-Tg annealing can be
combined to access a "forbidden glass" regime that is inaccessible through
thermal history or pressure history variation alone. We also study the relaxation
behavior of the densified samples during subsequent ambient pressure sub-Tg
annealing. Density and hardness are found to relax and approach their ambient
condition values upon annealing, but the difference in relaxation time of density
and hardness, which is usually observed for hot compressed glasses, vanishes for
samples previously subjected to high-pressure sub-Tg annealing. This confirms the
unique configurational state of these glasses.
PMID- 28418018
TI - Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the
Cerebral Cortex of Sanfilippo Syndrome IIIA Mice.
AB - Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that
specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The
accumulation of heparan sulfate results in neurological symptoms, culminating in
extensive neurodegeneration and early death. To study the impact of storage in
postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the
enzyme sulfamidase. We show that changes occur in excitatory postsynaptic
structure and function in the somatosensory cortex prior to signs of
neurodegeneration. These changes coincide with accumulation of heparan sulfate
with characteristic non-reducing ends, which is present at birth in the mutant
mice. Accumulation of heparan sulfate was also detected in primary cultures of
cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in
cultured astrocytes corresponded with augmented extracellular heparan sulfate and
glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice
showed enhanced ability to increase glutamate AMPA receptor subunits at the cell
surface of wild type neurons. These data support the idea that abnormalities in
heparan sulfate content and distribution contribute to alterations in
postsynaptic function. Our findings identify a disease-induced developmental
phenotype that temporally overlaps with the onset of behavioral changes in a
mouse model of MPS IIIA.
PMID- 28418020
TI - Pathogenic CD4+ T cells regulating B-cell differentiation in autoimmunity: not
exactly Tfh cells.
PMID- 28418019
TI - Live imaging of H3K9 acetylation in plant cells.
AB - Proper regulation of histone acetylation is important in development and cellular
responses to environmental stimuli. However, the dynamics of histone acetylation
at the single-cell level remains poorly understood. Here we established a
transgenic plant cell line to track histone H3 lysine 9 acetylation (H3K9ac) with
a modification-specific intracellular antibody (mintbody). The H3K9ac-specific
mintbody fused to the enhanced green fluorescent protein (H3K9ac-mintbody-GFP)
was introduced into tobacco BY-2 cells. We successfully demonstrated that H3K9ac
mintbody-GFP interacted with H3K9ac in vivo. The ratio of nuclear/cytoplasmic
H3K9ac-mintbody-GFP detected in quantitative analysis reflected the endogenous
H3K9ac levels. Under chemically induced hyperacetylation conditions with histone
deacetylase inhibitors including trichostatin A, Ky-2 and Ky-14, significant
enhancement of H3K9ac was detected by H3K9ac-mintbody-GFP dependent on the
strength of inhibitors. Conversely, treatment with a histone acetyltransferase
inhibitor, C646 caused a reduction in the nuclear to cytoplasmic ratio of H3K9ac
mintbody-GFP. Using this system, we assessed the environmental responses of
H3K9ac and found that cold and salt stresses enhanced H3K9ac in tobacco BY-2
cells. In addition, a combination of H3K9ac-mintbody-GFP with 5-ethynyl-2'
deoxyuridine labelling confirmed that H3K9ac level is constant during interphase.
PMID- 28418021
TI - Prion disease: Abeta pathology in human growth hormone recipients.
PMID- 28418022
TI - The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in
encephalitis.
AB - The discovery, in 2010, of autoantibodies against the extracellular proteins LGI1
and Caspr2 facilitated a change of view regarding the clinical importance of
voltage-gated potassium channel (VGKC) antibodies. Currently, these antibodies
are all classified as VGKC-complex antibodies, and are commonly considered to
have a similar clinical value. However, studies from the past few years show that
the immune responses mediated by these antibodies have differing clinical
relevance. Here, we review the clinical importance of these immune responses in
three settings: patients with anti-LGI1 antibodies, patients with anti-Caspr2
antibodies, and patients with antibodies against the VGKC complex that lack LGI1
and Caspr2 specificity. Antibodies against LGI1 and Caspr2 are associated with
different but well-defined syndromes, whereas the clinical importance of VGKC
complex antibodies without LGI1 and Caspr2 specificity is questionable. We
describe each of these syndromes, discuss the function of the target antigens and
review the limited paediatric literature on the topic. The findings emphasize the
importance of defining these disorders according to the molecular identity of the
targets (LGI1 or Caspr2), and caution against the use of VGKC-complex antibodies
for the diagnosis and treatment of patients without further definition of the
antigen.
PMID- 28418024
TI - Alzheimer disease: Neurofilament light in the blood marks Alzheimer degeneration.
PMID- 28418025
TI - Cerebrovascular disease: CeAD and migraine - an association built on shifting
sands.
PMID- 28418023
TI - Human induced pluripotent stem cells for modelling neurodevelopmental disorders.
AB - We currently have a poor understanding of the pathogenesis of neurodevelopmental
disorders, owing to the fact that postmortem and imaging studies can only measure
the postnatal status quo and offer little insight into the processes that give
rise to the observed outcomes. Human induced pluripotent stem cells (hiPSCs)
should, in principle, prove powerful for elucidating the pathways that give rise
to neurodevelopmental disorders. hiPSCs are embryonic-stem-cell-like cells that
can be derived from somatic cells. They retain the unique genetic signature of
the individual from whom they were derived, and thus enable researchers to
recapitulate that individual's idiosyncratic neural development in a dish. In the
case of individuals with disease, we can re-enact the disease-altered trajectory
of brain development and examine how and why phenotypic and molecular
abnormalities arise in these diseased brains. Here, we review hiPSC biology and
possible experimental designs when using hiPSCs to model disease. We then discuss
existing hiPSC models of neurodevelopmental disorders. Our hope is that, as some
studies have already shown, hiPSCs will illuminate the pathophysiology of
developmental disorders of the CNS and lead to therapeutic options for the
millions that are affected by these conditions.
PMID- 28418026
TI - The Cac2 subunit is essential for productive histone binding and nucleosome
assembly in CAF-1.
AB - Nucleosome assembly following DNA replication controls epigenome maintenance and
genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone
responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural
and functional details for this chaperone complex and its interaction with
histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass
spectrometry, combined with in vitro and in vivo mutagenesis studies, we
identified the regions involved in the direct interaction between the yeast CAF-1
subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large
subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is
mediated by a composite interface, shaped by Cac1-bound Cac2 and the Cac1 acidic
region. Cac2 is indispensable for productive histone binding, while deletion of
Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These
results define direct structural roles for yeast CAF-1 subunits and uncover a
previously unknown critical function of the middle subunit in CAF-1.
PMID- 28418027
TI - Accurate and reproducible invasive breast cancer detection in whole-slide images:
A Deep Learning approach for quantifying tumor extent.
AB - With the increasing ability to routinely and rapidly digitize whole slide images
with slide scanners, there has been interest in developing computerized image
analysis algorithms for automated detection of disease extent from digital
pathology images. The manual identification of presence and extent of breast
cancer by a pathologist is critical for patient management for tumor staging and
assessing treatment response. However, this process is tedious and subject to
inter- and intra-reader variability. For computerized methods to be useful as
decision support tools, they need to be resilient to data acquired from different
sources, different staining and cutting protocols and different scanners. The
objective of this study was to evaluate the accuracy and robustness of a deep
learning-based method to automatically identify the extent of invasive tumor on
digitized images. Here, we present a new method that employs a convolutional
neural network for detecting presence of invasive tumor on whole slide images.
Our approach involves training the classifier on nearly 400 exemplars from
multiple different sites, and scanners, and then independently validating on
almost 200 cases from The Cancer Genome Atlas. Our approach yielded a Dice
coefficient of 75.86%, a positive predictive value of 71.62% and a negative
predictive value of 96.77% in terms of pixel-by-pixel evaluation compared to
manually annotated regions of invasive ductal carcinoma.
PMID- 28418028
TI - An algorithm to predict advanced proximal colorectal neoplasia in Chinese
asymptomatic population.
AB - This study aims to develop and validate a new algorithm that incorporates distal
colonoscopic findings to predict advanced proximal neoplasia (APN) in a Chinese
asymptomatic population. We collected age, gender, and colonoscopic findings from
a prospectively performed colonoscopy study between 2013 and 2015 in a large
hospital-based endoscopy unit in Shanghai, China. Eligible subjects were
allocated to a derivation group (n = 3,889) and validation group (n = 1,944) by
random sampling. A new index for APN and its cut-off level were evaluated from
the derivation cohort by binary logistic regression. The model performance was
tested in the validation cohort using area under the curve (AUC). Age, gender,
and distal finding were found to be independent predictors of APN in the
derivation cohort (p < 0.001). Subjects were categorized into Average Risk (AR)
and High Risk (HR) based on a cut-off score of 2. The AUC of the derivation and
validation cohorts were 0.801 (0.754-0.847) and 0.722 (0.649-0.794),
respectively. In the validation cohort, those in the HR group had a 3.57 fold
higher risk of APN when compared with the AR group (P < 0.001), requiring 18 (95%
CI = 12-28) follow-up colonoscopies to detect 1 APN. This new clinical index is
useful to stratify APN risk in Chinese population.
PMID- 28418029
TI - TmCactin plays an important role in Gram-negative and -positive bacterial
infection by regulating expression of 7 AMP genes in Tenebrio molitor.
AB - Cactin was originally identified as an interactor of the Drosophila IkappaB
factor Cactus and shown to play a role in controlling embryonic polarity and
regulating the NF-kappaB signaling pathway. While subsequent studies have
identified the roles for Cactin in the mammalian immune response, the immune
function of Cactin in insects has not been described yet. Here, we identified a
Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and
characterized its functional role in innate immunity. TmCactin was highly
expressed in prepupa to last instar stages, and its expression was high in the
integument and Malpighian tubules of last instar larvae and adults. TmCactin was
induced in larvae after infection with different pathogens and detectable within
3 hours of infection. The highest levels of TmCactin expression were detected at
9 hours post infection. TmCactin RNAi significantly decreased the survival rates
of larvae after challenge with Escherichia coli and Staphylococcus aureus, but
had no significant effect after challenge with Candida albicans. Furthermore,
TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide
genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may
serve as an important regulator of innate immunity, mediating AMP responses
against both Gram-positive and Gram-negative bacteria in T. molitor.
PMID- 28418030
TI - The BMP2 nuclear variant, nBMP2, is expressed in mouse hippocampus and impacts
memory.
AB - The novel nuclear protein nBMP2 is synthesized from the BMP2 gene by
translational initiation at an alternative start codon. We generated a targeted
mutant mouse, nBmp2NLStm, in which the nuclear localization signal (NLS) was
inactivated to prevent nuclear translocation of nBMP2 while still allowing the
normal synthesis and secretion of the BMP2 growth factor. These mice exhibit
abnormal muscle function due to defective Ca2+ transport in skeletal muscle. We
hypothesized that neurological function, which also depends on intracellular Ca2+
transport, could be affected by the loss of nBMP2. Age-matched nBmp2NLStm and
wild type mice were analyzed by immunohistochemistry, behavioral tests, and
electrophysiology to assess nBMP2 expression and neurological function.
Immunohistochemical staining of the hippocampus detected nBMP2 in the nuclei of
CA1 neurons in wild type but not mutant mice, consistent with nBMP2 playing a
role in the hippocampus. Mutant mice showed deficits in the novel object
recognition task, suggesting hippocampal dysfunction. Electrophysiology
experiments showed that long-term potentiation (LTP) in the hippocampus, which is
dependent on intracellular Ca2+ transport and is thought to be the cellular
equivalent of learning and memory, was impaired. Together, these results suggest
that nBMP2 in the hippocampus impacts memory formation.
PMID- 28418031
TI - Serum Concentration of HDL Particles Predicts Mortality in Acute Heart Failure
Patients.
AB - Clinical studies have shown that assessing circulating concentrations of high
density lipoprotein (HDL) particles by nuclear magnetic resonance (NMR)
spectroscopy is superior to HDL-cholesterol in predicting cardiovascular risk. We
tested the hypothesis that circulating concentrations of HDL particles predict 3
month mortality of patients with acute heart failure (AHF). Out of 152 included
patients, 52% were female, additionally the mean patient age was 75.2 +/- 10.3
years, and three-month mortality was 27%. Serum lipoprotein profile at admission
was determined by NMR spectroscopy. Univariate logistic regression analyses
revealed a significant inverse association of total (odds ratio (OR) 0.38 per 1
SD increase, 95% confidence interval (CI) 0.23-0.60, p < 0.001) and small HDL
particle concentrations (OR 0.35 per 1-SD increase, 95% CI 0.19-0.60, p < 0.001)
with 3-month mortality, whereas concentrations of large HDL particles (p = 0.353)
or HDL-cholesterol (p = 0.107) showed no significant association. After
adjustment for age, sex, mean arterial pressure, low-density lipoprotein
cholesterol, glomerular filtration rate, urea, and N-terminal pro-brain
natriuretic peptide, both the total and small HDL particle concentrations
remained significantly associated with 3-month mortality. Based on our results,
we conclude that total and small HDL particle concentrations strongly and
independently predict 3-month mortality in AHF patients.
PMID- 28418032
TI - A New Approach to Evaluating Aberrant DNA Methylation Profiles in Hepatocellular
Carcinoma as Potential Biomarkers.
AB - Hypermethylation of CpG islands in the promoter region of tumor suppressor genes
(TSGs) and their subsequent silencing is thought to be one of the main mechanisms
of carcinogenesis. MBD2b enrichment coupled with a NimbleGen array was applied to
examine the genome-wide CpG island methylation profile of hepatocellular
carcinoma (HCC). Hypermethylated DNA of 58 pairs of HCC and adjacent tissue
samples was enriched and hybridized in the same array. Aberrant hypermethylated
peaks of HCC and adjacent tissues were screened and annotated after data
processing using NimbleScan2.5 and our newly developed Weighting and Scoring
(WAS) method, respectively. Validation using bisulfite sequencing of randomly
selected ANKRD45, APC, CDX1, HOXD3, PTGER and TUBB6 genes demonstrated
significant hypermethylation modification in HCC samples, consistent with the
array data.
PMID- 28418033
TI - A genome-wide SNP-based genetic map and QTL mapping for agronomic traits in
Chinese cabbage.
AB - The aim of this work was to construct a high-resolution genetic map for the
dissection of complex morphological and agronomic traits in Chinese cabbage
(Brassica rapa L. syn. B. campestris). Chinese cabbage, an economically important
vegetable, is a good model plant for studies on the evolution of morphologic
variation. Herein, two high-generation inbred Chinese cabbage lines,
'Huangxiaoza' and 'Bqq094-11', were crossed. Then restriction-site-associated DNA
sequencing (RAD-seq) was performed on the parents and 120 F2 individuals. A
genetic map containing 711 bins representing 3985 single nucleotide polymorphism
(SNP) markers was constructed. By using WinQTL with composite interval mapping
(CIM) and mixed-model based composite interval mapping (MCIM) analysis via
QTLNetwork, quantitative trait loci (QTL) linked to 16 genetic traits related to
plant size, color and leaf characteristics were mapped to 10 linkage groups. The
high density genetic map and QTL identified for morphological and agronomic
traits lay the groundwork for functional gene mapping, map-based cloning and
marker-assisted selection (MAS) in Chinese cabbage.
PMID- 28418034
TI - Light- and circadian-controlled genes respond to a broad light spectrum in Puffer
Fish-derived Fugu eye cells.
AB - Some cell lines retain intrinsic phototransduction pathways to control the
expression of light-regulated genes such as the circadian clock gene. Here we
investigated the photosensitivity of a Fugu eye, a cell line established from the
eye of Takifugu rubripes, to examine whether such a photosensitive nature is
present. Microarray analysis identified 15 genes that showed blue light-dependent
change at the transcript level. We investigated temporal profiles of the light
induced genes, as well as Cry and Per, under light-dark, constant light (LL), and
constant dark (DD) conditions by quantitative RT-PCR. Transcript levels of Per1a
and Per3 genes showed circadian rhythmic changes under both LL and DD conditions,
while those of Cry genes were controlled by light. All genes examined, including
DNA-damage response genes and photolyase genes, were upregulated not only by blue
light but also green and red light, implying the contribution of multiple
photopigments. The present study is the first to identify a photosensitive clock
cell line originating from a marine fish. These findings may help to characterize
the molecular mechanisms underlying photic synchronization of the physiological
states of fishes to not only daily light-dark cycles but also to various marine
environmental cycles such as the lunar or semi-lunar cycle.
PMID- 28418035
TI - Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.
AB - The medial prefrontal cortex (mPFC) plays a key role in top-down control of the
brain's stress axis, and its structure and function are particularly vulnerable
to stress effects, which can lead to depression in humans and depressive-like
states in animals. We tested whether chronic social defeat produces structural
alterations in the mPFC in mice. We first performed a microarray analysis of mPFC
gene expression changes induced by defeat, and biological pathway analysis
revealed a dominant pattern of down-regulation of myelin-associated genes.
Indeed, 69% of the most significantly down-regulated genes were myelin-related.
The down regulation was confirmed by in situ hybridization histochemistry for two
strongly down-regulated genes, myelin oligodendrocyte glycoprotein (Mog) and
ermin (Ermn), and by immunohistochemistry for myelin basic protein. To test for
stress-induced changes in myelin integrity, aurophosphate (Black Gold) myelin
staining was performed on mPFC sections. Quantitative stereologic analysis showed
reduced myelinated fiber length and density. Behavioral analysis confirmed that
the 14-day social defeat sessions resulted in induction of depressive-like states
measured in social interaction and light/dark tests. The combined data suggest
that chronic social defeat induces molecular changes that reduce myelination of
the prefrontal cortex, which may be an underlying basis for stress-induced
depressive states.
PMID- 28418036
TI - Maximal violation of Bell inequalities under local filtering.
AB - We investigate the behavior of the maximal violations of the CHSH inequality and
Vertesi's inequality under the local filtering operations. An analytical method
has been presented for general two-qubit systems to compute the maximal violation
of the CHSH inequality and the lower bound of the maximal violation of Vertesi's
inequality over the local filtering operations. We show by examples that there
exist quantum states whose non-locality can be revealed after local filtering
operation by the Vertesi's inequality instead of the CHSH inequality.
PMID- 28418037
TI - Mitochondrial C11orf83 is a potent Antiviral Protein Independent of interferon
production.
AB - Mitochondria have a central position in innate immune response via the adaptor
protein MAVS in mitochondrial outer membrane to limit viral replication by
inducing interferon production. Here, we reported that C11orf83, a component of
complex III of electronic transfer chain in mitochondrial inner membrane, was a
potent antiviral protein independent of interferon production. C11orf83
expression significantly increased in response to viral infection, and endows
cells with stronger capability of inhibiting viral replication. Deletion of
C11orf83 permits viral replication easier and cells were more vulnerable to viral
killing. These effects mainly were mediated by triggering OAS3-RNase L system.
C11orf83 overexpression induced higher transcription of OAS3, and knockdown
either OAS3 or RNase L impaired the antiviral capability of C11orf83.
Interestingly, the signaling from C11orf83 to OAS3-RNase L was independent of
interferon production. Thus, our findings suggested a new antiviral mechanism by
bridging cell metabolic machinery component with antiviral effectors.
PMID- 28418039
TI - Solution Process Synthesis of High Aspect Ratio ZnO Nanorods on Electrode Surface
for Sensitive Electrochemical Detection of Uric Acid.
AB - This study demonstrates a highly stable, selective and sensitive uric acid (UA)
biosensor based on high aspect ratio zinc oxide nanorods (ZNRs) vertical grown on
electrode surface via a simple one-step low temperature solution route. Uricase
enzyme was immobilized on the ZNRs followed by Nafion covering to fabricate UA
sensing electrodes (Nafion/Uricase-ZNRs/Ag). The fabricated electrodes showed
enhanced performance with attractive analytical response, such as a high
sensitivity of 239.67 MUA cm-2 mM-1 in wide-linear range (0.01-4.56 mM), rapid
response time (~3 s), low detection limit (5 nM), and low value of apparent
Michaelis-Menten constant (Kmapp, 0.025 mM). In addition, selectivity,
reproducibility and long-term storage stability of biosensor was also
demonstrated. These results can be attributed to the high aspect ratio of
vertically grown ZNRs which provides high surface area leading to enhanced enzyme
immobilization, high electrocatalytic activity, and direct electron transfer
during electrochemical detection of UA. We expect that this biosensor platform
will be advantageous to fabricate ultrasensitive, robust, low-cost sensing device
for numerous analyte detection.
PMID- 28418038
TI - 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF
as an m5C reader.
AB - 5-methylcytosine (m5C) is a post-transcriptional RNA modification identified in
both stable and highly abundant tRNAs and rRNAs, and in mRNAs. However, its
regulatory role in mRNA metabolism is still largely unknown. Here, we reveal that
m5C modification is enriched in CG-rich regions and in regions immediately
downstream of translation initiation sites and has conserved, tissue-specific and
dynamic features across mammalian transcriptomes. Moreover, m5C formation in
mRNAs is mainly catalyzed by the RNA methyltransferase NSUN2, and m5C is
specifically recognized by the mRNA export adaptor ALYREF as shown by in vitro
and in vivo studies. NSUN2 modulates ALYREF's nuclear-cytoplasmic shuttling, RNA
binding affinity and associated mRNA export. Dysregulation of ALYREF-mediated
mRNA export upon NSUN2 depletion could be restored by reconstitution of wild-type
but not methyltransferase-defective NSUN2. Our study provides comprehensive m5C
profiles of mammalian transcriptomes and suggests an essential role for m5C
modification in mRNA export and post-transcriptional regulation.
PMID- 28418040
TI - The Height-Width-Depth Ratios of the Intervertebral Discs and Vertebral Bodies in
Adolescent Idiopathic Scoliosis vs Controls in a Chinese Population.
AB - Adolescent idiopathic scoliosis (AIS) patients have been reported to be taller
and more slender than normal controls, suggesting less mechanical stiffness of
their trunk and spine. For assessment of mechanical stiffness, to our best
knowledge this is the first to study height-width-depth relations at the level of
the individual vertebra and disc in 3-D and to evaluate its relation with the
Cobb angle severity. A unique series of high-resolution pre-operative computed
tomographic (CT) scans of a total of 105 Chinese patients with moderate to severe
AIS and 11 age-matched non-scoliotic controls were used for this study. It was
found that some geometric relations differed between primary thoracic curves,
secondary curves and normal controls at the individual affected vertebra and disc
level. The scoliotic discs in the primary curves were relatively more slender
(taller and thinner) than in secondary curves and as compared to controls. In the
lumbar spinal area, the vertebral bodies were more slender in the primary as well
as secondary AIS curves as compared to the controls. Therefore, if all material
properties remain the same, our finding indicates that scoliotic spines may be
mechanically less stiff than normal spines. No significant correlation between
any of the measures and Cobb angle severity was found.
PMID- 28418041
TI - Highly sensitive strain sensor based on helical structure combined with Mach
Zehnder interferometer in multicore fiber.
AB - Optical fiber sensors for strain measurement have been playing important roles in
structural health monitoring for buildings, tunnels, pipelines, aircrafts, and so
on. A highly sensitive strain sensor based on helical structures (HSs) assisted
Mach-Zehnder interference in an all-solid heterogeneous multicore fiber (MCF) is
proposed and experimentally demonstrated. Due to the HSs, a maximum strain
sensitivity as high as -61.8 pm/MUepsilon was experimentally achieved. This is
the highest sensitivity among interferometer-based strain sensors reported so
far, to the best of our knowledge. Moreover, the proposed sensor has the ability
to discriminate axial strain and temperature, and offers several advantages such
as repeatability of fabrication, robust structure and compact size, which further
benefits its practical sensing applications.
PMID- 28418042
TI - Selective orbital reconstruction in tetragonal FeS: A density functional
dynamical mean-field theory study.
AB - Transport properties of tetragonal iron monosulfide, mackinawite, show a range of
complex features. Semiconductive behavior and proximity to metallic states with
nodal superconductivity mark this d-band system as unconventional quantum
material. Here, we use the density functional dynamical mean-field theory
(DFDMFT) scheme to comprehensively explain why tetragonal FeS shows both
semiconducting and metallic responses in contrast to tetragonal FeSe which is a
pseudogaped metal above the superconducting transition temperature. Within local
density-approximation plus dynamical mean-field theory (LDA+DMFT) we characterize
its paramagnetic insulating and metallic phases, showing the proximity of
mackinawite to selective Mott localization. We report the coexistence of
pseudogaped and anisotropic Dirac-like electronic dispersion at the border of the
Mott transition. These findings announce a new understanding of many-particle
physics in quantum materials with coexisting Dirac-fermions and pseudogaped
electronic states at low energies. Based on our results we propose that in
electron-doped FeS substantial changes would be seen when the metallic regime was
tuned towards an electronic state that hosts unconventional superconductivity.
PMID- 28418044
TI - Design of liquid crystals with 'de Vries-like' properties: structural variants of
carbosilane-terminated 5-phenylpyrimidine mesogens.
AB - Structural variants of the 'de Vries-like' mesogen 5-[4-(12,12,14,14,16,16
hexamethyl-12,14,16-trisilaheptadecyloxy)phenyl]-2-hexyloxypyrimidine (QL16-6),
including two isomers with branched iso-tricarbosilane end-groups, were
synthesized and their mesomorphic and 'de Vries-like' properties were
characterized by polarized optical microscopy, differential scanning calorimetry,
small angle and 2D X-ray scattering techniques. A comparative analysis of isomers
with linear and branched tricarbosilane end-groups shows that they exhibit
comparable mesomorphic and 'de Vries-like' properties. Furthermore, the
difference in effective molecular length Leff between the linear and branched
isomers in the SmA and SmC phases (ca. 4-5 A), which was derived from 2D X-ray
scattering experiments, suggests that the linear tricarbosilane end-group is
hemispherical in shape on the time-average, as predicted by a DFT conformational
analysis at the B3LYP/6-31G* level.
PMID- 28418043
TI - Predicting Protein-protein Association Rates using Coarse-grained Simulation and
Machine Learning.
AB - Protein-protein interactions dominate all major biological processes in living
cells. We have developed a new Monte Carlo-based simulation algorithm to study
the kinetic process of protein association. We tested our method on a previously
used large benchmark set of 49 protein complexes. The predicted rate was
overestimated in the benchmark test compared to the experimental results for a
group of protein complexes. We hypothesized that this resulted from molecular
flexibility at the interface regions of the interacting proteins. After applying
a machine learning algorithm with input variables that accounted for both the
conformational flexibility and the energetic factor of binding, we successfully
identified most of the protein complexes with overestimated association rates and
improved our final prediction by using a cross-validation test. This method was
then applied to a new independent test set and resulted in a similar prediction
accuracy to that obtained using the training set. It has been thought that
diffusion-limited protein association is dominated by long-range interactions.
Our results provide strong evidence that the conformational flexibility also
plays an important role in regulating protein association. Our studies provide
new insights into the mechanism of protein association and offer a
computationally efficient tool for predicting its rate.
PMID- 28418045
TI - Correction: A molecular dynamics study of the ionic liquid, choline acetate.
AB - Correction for 'A molecular dynamics study of the ionic liquid, choline acetate'
by Jon A. L. Willcox et al., Phys. Chem. Chem. Phys., 2016, 18, 14850-14858.
PMID- 28418046
TI - Novel nickel(ii) complexes of sterically modified linear N4 ligands: effect of
ligand stereoelectronic factors and solvent of coordination on nickel(ii) spin
state and catalytic alkane hydroxylation.
AB - A series of Ni(ii) complexes of the types [Ni(L)(CH3CN)2](BPh4)21-3, 5 and
[Ni(L4)](BPh4)24, where L = N,N'-bis(2-pyrid-2-ylmethyl)-1,4-diazepane (L1), N-(6
methylpyrid-2-ylmethyl)-N'-(pyrid-2-ylmethyl)-1,4-diazepane (L2), N,N'-bis(6
methyl-2-pyridylmethyl)-1,4-diazepane (L3), N,N'-dimethyl-N,N'-bis(2
pyridylmethyl)ethylenediamine (L5) and L4 = N,N'-bis((1-methyl-1H-imidazole-2
yl)methyl)-1,4-diazepane, have been isolated and characterized. The complex
cations of 1 and 4 possess, respectively, distorted octahedral and low-spin
square planar coordination geometries in which nickel(ii) is meridionally
coordinated to all four nitrogen atoms of L1 and L4. DFT studies reveal that L5
with the ethylenediamine backbone coordinates in the cis-beta mode in
[Ni(L5)(CH3CN)2]2+5, but in the cis-alpha mode in [Ni(L5)(H2O)2]2+. Also, they
illustrate the role of ligand donor atom type, diazacyclo backbone and steric
hindrance to coordination of pyridyl nitrogen in conferring novel coordination
geometries on Ni(ii). All these complexes catalyse the oxidation of cyclohexane
in the presence of m-CPBA as the oxidant up to 600 turnover numbers (TON) with
relatively good alcohol selectivity (A/K, 5.6-7.2). Adamantane is oxidized to 1
adamantanol, 2-adamantanol and 2-adamantanone with high bond selectivity (3
degrees /2 degrees , 8.7-11.7). The incorporation of methyl substituent(s) on one
(2) or both (3) of the pyridyl rings and the replacement of both the
pyridylmethyl arms in 1 by imidazolylmethyl arms to give 4 decrease the catalytic
efficiency. Interestingly, 5 with the cis-beta mode of coordination provides two
labile cis coordination sites for oxidant binding, leading to higher total TON
and product/bond selectivity.
PMID- 28418047
TI - An FTIR emission study of the products of NO A2Sigma+ (v = 0, 1) + O2 collisions.
AB - Collisional quenching of NO A2Sigma+ (v = 0, 1) by O2 has been studied through
the detection of vibrationally excited products by time-resolved Fourier
transform infrared emission spectroscopy. Non-reactive quenching of NO A2Sigma+
(v = 0) produces a vibrational distribution in NO X2Pi which has been quantified
for v = 2-22, and is found to be bimodal. The results are consistent with two
quenching channels. The first forms the ground X3Sigma or low-lying a 1Deltag
electronic state of O2 with a distribution including high vibrational levels of
NO X2Pi which is slightly hotter than statistical. Two possibilities are
identified for the second channel. The first, with a similar quantum yield to
that producing higher vibrational levels, forms a highly electronically excited
state, such as O2 c1Sigma, with low vibrational levels in NO X2Pi which are
inverted with a distribution resembling that resulting from a sudden or harpoon
mechanism. The second is that ground state oxygen is formed with low vibrational
energy partitioned into NO X2Pi. In addition, vibrationally excited NO2 is
observed, but at intensities which indicate that it is formed in low quantum
yield. Quantitatively unobservable processes (defined as those which do not form
ground state NO (v >= 2)) are found to have a branching ratio of at most 25 +/-
5%. The results are compared with those of previous studies and the most
consistent interpretation suggests that dissociation of O2 to form ground state
O(3P) atoms and ground vibrational state NO X2Pi (v = 0) is the main reactive
process rather than NO2 formation. Qualitatively similar results are seen for the
quenching of NO A2Sigma+ (v = 1).
PMID- 28418048
TI - DNA-spheres decorated with magnetic nanocomposites based on terminal transfer
reactions for versatile target detection and cellular targeted drug delivery.
AB - We present an elegant approach to make a magnetic nanoparticle (MNP) conjugated
DNA-sphere (MNP/DNA-SP) which is integrated with disulfide (MNP/DS-SP) or an
aptamer (MNP/sgc8-SP) for GSH detection, selective cancer cell recognition,
effective drug delivery, and bioimaging.
PMID- 28418049
TI - Systems chemistry.
AB - Building on our ability to design and synthesise molecules and our understanding
of the noncovalent interactions between these molecules, the chemical sciences
are currently entering the new territory of Systems Chemistry. This young field
aims to develop complex molecular systems showing emergent properties; i.e.
properties that go beyond the sum of the characteristics of the individual
consituents of the system. This review gives an impression of the state of the
art of the field by showing a diverse number of recent highlights, including out
of-equilibrium self-assembly, chemically fuelled molecular motion,
compartmentalised chemical networks and designed oscillators. Subsequently a
number of current challenges related to the design of complex chemical systems
are discussed, including those of creating concurrent formation-destruction
systems, continuously maintaining chemical systems away from equilibrium,
incorporating feedback loops and pushing replication chemistry away from
equilibrium. Finally, the prospects for Systems Chemistry are discussed including
the tantalizing vision of the de novo synthesis of life and the idea of self
synthesising and self-repairing chemical factories.
PMID- 28418051
TI - A structural bioinformatics investigation on protein-DNA complexes delineates
their modes of interaction.
AB - The lifetimes of protein-DNA adducts are strictly related to the various protein
functions. This feature must be encoded by the amino acids located at the protein
DNA interface. The large number of structurally characterized protein-DNA
complexes now available from the Protein Data Bank (PDB) allows extensive
structural bioinformatics investigations on protein-DNA interfaces. The modes of
protein binding to DNA have been explored by dividing 629 non-redundant PDB files
of protein-DNA complexes into separate classes for structural proteins,
transcription factors and DNA-related enzymes. From the selected PDB structures,
we could define 2953 protein-DNA contact regions. A systematic analysis of amino
acid occurrences at these protein-DNA contact regions yielded composition
profiles, which are typical for each of the three protein classes. The critical
role of some amino acids to influence intermolecular contact lifetimes is
discussed here. The occurrence of arginine at the protein-DNA interface, by far
the most abundant amino acid in this protein moiety, is found to be the main
feature that differentiates proteins from the three classes. Structural proteins
and, to a lesser extent, transcription factors exhibit the highest Arg occurrence
at protein-DNA contact regions. Reduced Arg/Lys ratios together with increased
contents of Asp and Glu are observed in all the DNA-interacting enzymes. The
amount of negatively charged side chains, highly conserved among homologous DNA
related enzymes at protein-DNA interfaces, is suggested as a tool to modulate
protein mobility along DNA chains. Arg/Lys, Asp/Asn and Glu/Gln substitutions at
protein-DNA interfaces may represent a very feasible way to control protein
motion on DNA rails.
PMID- 28418050
TI - Reversible helical chirality of perylene bisimide aggregates: amino acid-directed
chiral transfer and chiral inversion.
AB - Through the formation of dynamic covalent bonds, we succeeded, for the first
time, in achieving a reversible chiral transfer from amino acids to perylene
bisimide aggregates in aqueous solutions. Two opposite helical aggregations are
induced with l-phenylalanine and l-tyrosine, respectively. It is possible that
the change in configurations of phenyl groups in amino acids leads to the chiral
inversion of BAPBI arrangements.
PMID- 28418052
TI - Thermal spin-crossover with a large hysteresis spanning room temperature in a
mononuclear complex.
AB - A large hysteresis centered around room temperature represents one of the
mandatory goals of research on functional switchable materials. In the thoroughly
studied field of spin-crossover, such behaviour appears very rarely and
essentially concerns coordination networks. A new compound showing a large spin
crossover hysteresis spanning room temperature demonstrates in a definitive
manner that this goal is achievable in molecular discrete compounds without
damaging the single-crystal character.
PMID- 28418053
TI - A new route for the preparation of enriched iso-polylactide from rac-lactide via
a Lewis acid catalyzed ring-opening of an epoxide.
AB - Tetraphenylporphyrin aluminum(iii) salts, TPPAlX, where X = Me, OEt, OiPr,
OCHMeCH2Cl, and Cl, and bis(triphenylphosphine)imminium chloride, PPN+Cl- (1 : 1)
react with rac-lactide, rac-LA, in neat propylene oxide, PO, to yield chains of
enriched isotactic polylactide, PLA, with end groups of PO-Cl and with time these
yield cyclic polymers (PO)n(PLA) where n = 2 or 3 and even higher. There is no
reaction between TPPAlOR (R = Et or iPr), PPN+Cl-, and rac-LA in neat THF at 25
degrees C even though TPPAlOR (R = Et or iPr) and PPN+Cl- in neat PO yields
polypropylene oxide with a terminal OR group, H(PO)nOR. Taken together, Al(iii)
acts as a Lewis acid in the ring-opening of PO, in which PPN+Cl- is present and
the incipient ClCH2CHMeO- initiates the ROP of LA to yield anion chains of [(PLA)
OCHMeCH2Cl]-, and then the ring-opening of PO yields cycles, (PO)n(PLA), with the
liberation of Cl-. The polymer was isolated by the addition of MeOH/HCl and end
group analysis by mass spectrometry.
PMID- 28418054
TI - Addressing uncertainty in atomistic machine learning.
AB - Machine-learning regression has been demonstrated to precisely emulate the
potential energy and forces that are output from more expensive electronic
structure calculations. However, to predict new regions of the potential energy
surface, an assessment must be made of the credibility of the predictions. In
this perspective, we address the types of errors that might arise in atomistic
machine learning, the unique aspects of atomistic simulations that make machine
learning challenging, and highlight how uncertainty analysis can be used to
assess the validity of machine-learning predictions. We suggest this will allow
researchers to more fully use machine learning for the routine acceleration of
large, high-accuracy, or extended-time simulations. In our demonstrations, we use
a bootstrap ensemble of neural network-based calculators, and show that the width
of the ensemble can provide an estimate of the uncertainty when the width is
comparable to that in the training data. Intriguingly, we also show that the
uncertainty can be localized to specific atoms in the simulation, which may offer
hints for the generation of training data to strategically improve the machine
learned representation.
PMID- 28418055
TI - Application of machine/statistical learning, artificial intelligence and
statistical experimental design for the modeling and optimization of methylene
blue and Cd(ii) removal from a binary aqueous solution by natural walnut carbon.
AB - Analytical chemists apply statistical methods for both the validation and
prediction of proposed models. Methods are required that are adequate for finding
the typical features of a dataset, such as nonlinearities and interactions.
Boosted regression trees (BRTs), as an ensemble technique, are fundamentally
different to other conventional techniques, with the aim to fit a single
parsimonious model. In this work, BRT, artificial neural network (ANN) and
response surface methodology (RSM) models have been used for the optimization
and/or modeling of the stirring time (min), pH, adsorbent mass (mg) and
concentrations of MB and Cd2+ ions (mg L-1) in order to develop respective
predictive equations for simulation of the efficiency of MB and Cd2+ adsorption
based on the experimental data set. Activated carbon, as an adsorbent, was
synthesized from walnut wood waste which is abundant, non-toxic, cheap and
locally available. This adsorbent was characterized using different techniques
such as FT-IR, BET, SEM, point of zero charge (pHpzc) and also the determination
of oxygen containing functional groups. The influence of various parameters (i.e.
pH, stirring time, adsorbent mass and concentrations of MB and Cd2+ ions) on the
percentage removal was calculated by investigation of sensitive function,
variable importance rankings (BRT) and analysis of variance (RSM). Furthermore, a
central composite design (CCD) combined with a desirability function approach
(DFA) as a global optimization technique was used for the simultaneous
optimization of the effective parameters. The applicability of the BRT, ANN and
RSM models for the description of experimental data was examined using four
statistical criteria (absolute average deviation (AAD), mean absolute error
(MAE), root mean square error (RMSE) and coefficient of determination (R2)). All
three models demonstrated good predictions in this study. The BRT model was more
precise compared to the other models and this showed that BRT could be a powerful
tool for the modeling and optimizing of removal of MB and Cd(ii). Sensitivity
analysis (calculated from the weight of neurons in ANN) confirmed that the
adsorbent mass and pH were the essential factors affecting the removal of MB and
Cd(ii), with relative importances of 28.82% and 38.34%, respectively. A good
agreement (R2 > 0.960) between the predicted and experimental values was
obtained. Maximum removal (R% > 99) was achieved at an initial dye concentration
of 15 mg L-1, a Cd2+ concentration of 20 mg L-1, a pH of 5.2, an adsorbent mass
of 0.55 g and a time of 35 min.
PMID- 28418056
TI - Unprecedented thermal condensation of tetracyanocyclopropanes to
triazaphenalenes: a facile route for the design of novel materials for electronic
applications.
AB - We report an unusual thermal condensation of readily available
tetracyanocyclopropanes to tetracyanosubstituted triazaphenalenes, which revealed
interesting optoelectronic properties such as strongly pronounced solvatochromism
and bright photoluminescence. Optical memory elements and organic light emitting
diodes with a deep red electroluminescence were designed using triazaphenalenes,
thus highlighting the potential of these compounds as materials for electronic
applications.
PMID- 28418057
TI - Geometry-dependent compressive responses in nanoimprinted submicron-structured
shape memory polyurethane.
AB - High resolution surface textures, when rationally designed, provide an attractive
surface engineering approach to enhance surface functionalities. Designing smart
surfaces by coupling surface texture with shape memory polymers has garnered
attention in achieving tunable mechanical properties. We investigate the
structure-mechanical property relationships for programmable, shape-memorizing
submicron-scale pillar arrays subjected to flat-punch compression. The
geometrically-dependent deformation of structured surfaces with two different
aspect ratios (250 nm-pillars 1 : 1 and 550 nm-pillars 2.4 : 1) were
investigated, and their moduli were found to be lower than that of non-patterned
surface. From finite element analysis, the pillar deformation is correlated to a
mechanistic transition from a discrete, unidirectional compression of 250 nm
pillars to lateral constraints caused by interpillar contact in 550 nm-pillars.
This lateral pillar-pillar contact in the 550 nm-pillars resulted in an increased
and maximum strain-dependent modulus but lower elastic recovery and energy
dissipation as compared with the 250 nm-pillars. Furthermore, the compressive
responses of temporarily shaped pillars (programmed by stretching) were compared
with the permanently shaped pillars. The extent of lateral constraints controlled
by pillar shape and spacing in 550 nm-pillars was responsible for the modulus
differences between the original and stretched patterns, whereas the modulus of
250 nm-pillars remained as a constant value with different levels of stretching.
This study provides mechanistic insights into how the mechanical behavior can be
modulated by designing the aspect ratio of shape memory pillar arrays and by
programming the surface geometry, thus revealing the potential of developing
ingenious designs of responsive surfaces sensitive to mechanical deformation.
PMID- 28418058
TI - Crystalline nanotubular framework constructed by cucurbit[8]uril for selective
CO2 adsorption.
AB - A crystalline nanotubular framework was constructed by cucurbit[8]uril (CB[8])
molecules in the presence of a molecular chaperone. Compared with amorphous
CB[8], the framework exhibits highly selective adsorption for CO2 over N2, CH4,
and H2.
PMID- 28418059
TI - Hybrid micro-/nano-structures derived from metal-organic frameworks: preparation
and applications in energy storage and conversion.
AB - Metal-organic frameworks (MOFs), an important class of inorganic-organic hybrid
crystals with intrinsic porous structures, can be used as versatile precursors or
sacrificial templates for preparation of numerous functional nanomaterials for
various applications. Recent developments of MOF-derived hybrid micro-/nano
structures, constructed by more than two components with varied functionalities,
have revealed their extensive capabilities to overcome the weaknesses of the
individual counterparts and thus give enhanced performance for energy storage and
conversion. In this tutorial review, we summarize the recent advances in MOF
derived hybrid micro-/nano-structures. The synthetic strategies for preparing MOF
derived hybrid micro-/nano-structures are first introduced. Focusing on energy
storage and conversion, we then discuss their potential applications in lithium
ion batteries, lithium-sulfur batteries, supercapacitors, lithium-oxygen
batteries and fuel cells. Finally, we give our personal insights into the
challenges and opportunities for the future research of MOF-derived hybrid micro
/nano-structures.
PMID- 28418060
TI - Reaction chemistry in rechargeable Li-O2 batteries.
AB - The seemingly simple reaction of Li-O2 batteries involving lithium and oxygen
makes this chemistry attractive for high-energy-density storage systems; however,
achieving this reaction in practical rechargeable Li-O2 batteries has proven
difficult. The reaction paths leading to the final Li2O2 discharge products can
be greatly affected by the operating conditions or environment, which often
results in major side reactions. Recent research findings have begun to reveal
how the reaction paths may be affected by the surrounding conditions and to
uncover the factors contributing to the difficulty in achieving the reactions of
lithium and oxygen. This progress report describes the current state of
understanding of the electrode reaction mechanisms in Li-O2 batteries; the
factors that affect reaction pathways; and the effect of cell components such as
solvents, salts, additives, and catalysts on the discharge product and its
decomposition during charging. This comprehensive review of the recent progress
in understanding the reaction chemistry of the Li-O2 system will serve as
guidelines for future research and aid in the development of reliable high-energy
density rechargeable Li-O2 batteries.
PMID- 28418061
TI - Self-powered electrochemical systems as neurochemical sensors: toward self
triggered in vivo analysis of brain chemistry.
AB - Real-time in vivo analysis of neurochemical dynamics has great physiological and
pathological implications for a full understanding of the brain. Self-powered
electrochemical systems (SPESs) built on galvanic cell configurations bear the
advantages of easy miniaturization for implantation and no interference to
electric activities of neurons over traditional externally-powered
electrochemical sensors for self-triggered in vivo analysis. However, this is
still a new concept for in vivo neurochemical sensing with few implanted examples
reported so far. This tutorial review summarizes the development of SPESs toward
implantable applications from both principal and practical perspectives,
ultimately aimed at providing a guide map to the future design of neurochemical
sensors for in vivo analysis of brain chemistry.
PMID- 28418062
TI - Flexible aspartates propel iron to the ferroxidation sites along pathways
stabilized by a conserved arginine in Dps proteins from Mycobacterium smegmatis.
AB - DNA-binding proteins under starvation (Dps) are dodecameric nano-compartments for
iron oxidation and storage in bacterial cells. These proteins have roughly
spherical structures with a hollow interior where iron is stored. Through
mutational analysis of a conserved arginine residue in the second Dps protein
from Mycobacterium smegmatis, we have identified residues which stabilize the
interfaces between the iron entry and ferroxidation sites. Also, we have used X
ray crystallography to determine the structures of co-crystals of iron and Dps in
varying proportions and compare the changes in these ligand-bound forms with
respect to the apo-protein. The iron-loaded proteins of low, medium and high iron
bound forms were found to exhibit aspartate residues with alternate
conformations, some of which could be directly linked to the sites of
ferroxidation and iron entry. We conclude that the increased flexibility of
aspartates in the presence of iron facilitates its movement from the entry site
to the ferroxidaton site, and the two active sites are stabilized by the
interactions of a conserved arginine residue R73.
PMID- 28418063
TI - Ab initio modelling of oxygen vacancy arrangement in highly defective HfO2
resistive layers.
AB - We report ab initio results for sub-stoichiometric HfOx with different oxygen
vacancy densities, useful in exploring microscopic mechanisms that govern the
operation of RRAM devices. We demonstrate that oxygen vacancy filaments are
energetically more stable than randomly distributed defects. Furthermore, the
stability of the filaments increases with the number of confined oxygen
vacancies. Energetic and structural analyses show that bonds between neighboring
coordinative unsaturated Hf atoms promote filament stability, and electron
trapping, due to electron injection, increases the cohesive energy until the
injection is moderate. The highly oxygen deficient configuration of the filaments
leads to a substantial lowering of the HfOx band gap, which locally increases the
conductivity of the system. Charge injection and electric fields modify the
mobility of oxygen ions in the proximity of the filament. The simulations suggest
that oxygen ion diffusion can lead to an asymmetric reduction of filament
thickness and thus to its progressive disruption where the vacancy cohesion
energy is lower.
PMID- 28418064
TI - Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) explored as a potential
electrochemical sensor for dopamine: surfactants significantly influence sensor
capabilities.
AB - Surfactant exfoliated 2D hexagonal Boron Nitride (2D-hBN) nanosheets are explored
as a potential electrochemical sensing platform and evaluated towards the
electroanalytical sensing of dopamine (DA) in the presence of the common
interferents, ascorbic acid (AA) and uric acid (UA). Surfactant exfoliated 2D-hBN
nanosheets (2-4 layers) fabricated using sodium cholate in aqueous media are
electrically wired via a drop-casting modification process onto disposable screen
printed graphite electrodes (SPEs). We critically evaluate the performance of
these 2D-hBN modified SPEs and demonstrate the effect of 'mass coverage' towards
the detection of DA, AA and UA. Previous studies utilising surfactant-free
(pristine) 2D-hBN modified SPEs have shown a beneficial effect towards the
detection of DA, AA and UA when compared to the underlying/unmodified graphite
based electrode. We show that the fabrication route utilised to prepare 2D-hBN is
a vital experimental consideration, such that the beneficial effect previously
reported is considerably reduced when surfactant exfoliated 2D-hBN is utilised.
We demonstrate for the first time, through implementation of control experiments
in the form of surfactant modified graphite electrodes, that sodium cholate is a
major contributing factor to the aforementioned detrimental behaviour. The
significance here is not in the material per se, but the fundamental knowledge of
the surfactant and surface coverage changing the electrochemical properties of
the material under investigation. Given the wide variety of ionic and non-ionic
surfactants that are utilised in the manufacture of novel 2D materials, the
control experiments reported herein need to be performed in order to de-convolute
the electrochemical response and effectively evaluate the 'underlying
surface/surfactant/2D materials' electrocatalytic contribution.
PMID- 28418065
TI - Vitamin E for Alzheimer's dementia and mild cognitive impairment.
AB - BACKGROUND: Vitamin E occurs naturally in the diet. It has several biological
activities, including functioning as an antioxidant to scavenge toxic free
radicals. Evidence that free radicals may contribute to the pathological
processes behind cognitive impairment has led to interest in the use of vitamin E
supplements to treat mild cognitive impairment (MCI) and Alzheimer's disease
(AD). This is an update of a Cochrane Review first published in 2000, and
previously updated in 2006 and 2012. OBJECTIVES: To assess the efficacy of
vitamin E in the treatment of MCI and dementia due to AD. SEARCH METHODS: We
searched the Specialized Register of the Cochrane Dementia and Cognitive
Improvement Group (ALOIS), the Cochrane Library, MEDLINE, Embase, PsycINFO,
CINAHL, LILACS as well as many trials databases and grey literature sources on 22
April 2016 using the terms: "Vitamin E", vitamin-E, alpha-tocopherol. SELECTION
CRITERIA: We included all double-blind, randomised trials in which treatment with
any dose of vitamin E was compared with placebo in people with AD or MCI. DATA
COLLECTION AND ANALYSIS: We used standard methodological procedures according to
the Cochrane Handbook for Systematic Reviews of Interventions. We rated the
quality of the evidence using the GRADE approach. Where appropriate we attempted
to contact authors to obtain missing information. MAIN RESULTS: Four trials met
the inclusion criteria, but we could only extract outcome data in accordance with
our protocol from two trials, one in an AD population (n = 304) and one in an MCI
population (n = 516). Both trials had an overall low to unclear risk of bias. It
was not possible to pool data across studies owing to a lack of comparable
outcome measures.In people with AD, we found no evidence of any clinically
important effect of vitamin E on cognition, measured with change from baseline in
the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) over six
to 48 months (mean difference (MD) -1.81, 95% confidence interval (CI) -3.75 to
0.13, P = 0.07, 1 study, n = 272; moderate quality evidence). There was no
evidence of a difference between vitamin E and placebo groups in the risk of
experiencing at least one serious adverse event over six to 48 months (risk ratio
(RR) 0.86, 95% CI 0.71 to 1.05, P = 0.13, 1 study, n = 304; moderate quality
evidence), or in the risk of death (RR 0.84, 95% CI 0.52 to 1.34, P = 0.46, 1
study, n = 304; moderate quality evidence). People with AD receiving vitamin E
showed less functional decline on the Alzheimer's Disease Cooperative
Study/Activities of Daily Living Inventory than people receiving placebo at six
to 48 months (mean difference (MD) 3.15, 95% CI 0.07 to 6.23, P = 0.04, 1 study,
n = 280; moderate quality evidence). There was no evidence of any clinically
important effect on neuropsychiatric symptoms measured with the Neuropsychiatric
Inventory (MD -1.47, 95% CI -4.26 to 1.32, P = 0.30, 1 study, n = 280; moderate
quality evidence).We found no evidence that vitamin E affected the probability of
progression from MCI to probable dementia due to AD over 36 months (RR 1.03, 95%
CI 0.79 to 1.35, P = 0.81, 1 study, n = 516; moderate quality evidence). Five
deaths occurred in each of the vitamin E and placebo groups over the 36 months
(RR 1.01, 95% CI 0.30 to 3.44, P = 0.99, 1 study, n = 516; moderate quality
evidence). We were unable to extract data in accordance with the review protocol
for other outcomes. However, the study authors found no evidence that vitamin E
differed from placebo in its effect on cognitive function, global severity or
activities of daily living . There was also no evidence of a difference between
groups in the more commonly reported adverse events. AUTHORS' CONCLUSIONS: We
found no evidence that the alpha-tocopherol form of vitamin E given to people
with MCI prevents progression to dementia, or that it improves cognitive function
in people with MCI or dementia due to AD. However, there is moderate quality
evidence from a single study that it may slow functional decline in AD. Vitamin E
was not associated with an increased risk of serious adverse events or mortality
in the trials in this review. These conclusions have changed since the previous
update, however they are still based on small numbers of trials and participants
and further research is quite likely to affect the results.
PMID- 28418066
TI - A National Survey on the Effect of the Geriatric Academic Career Award in
Advancing Academic Geriatric Medicine.
AB - A workforce that understands principles of geriatric medicine is critical to
addressing the care needs of the growing elderly population. This will be
impossible without a substantial increase in academicians engaged in education
and aging research. Limited support of early-career clinician-educators is a
major barrier to attaining this goal. The Geriatric Academic Career Award (GACA)
was a vital resource that benefitted 222 junior faculty members. GACA
availability was interrupted in 2006, followed by permanent discontinuation after
the Geriatrics Workforce Education Program (GWEP) subsumed it in 2015, leaving
aspiring clinician-educators with no similar alternatives. GACA recipients were
surveyed in this cross-sectional, multimethod study to assess the effect of the
award on career development, creation and dissemination of educational products,
funding discontinuation consequences, and implications of program closure for the
future of geriatric health care. Uninterrupted funding resulted in fulfillment of
GACA goals (94%) and overall career success (96%). Collectively, awardees reached
more than 40,700 learners. Funding interruption led to 55% working additional
hours over and above an increased clinical workload to continue their GACA
related research and scholarship. Others terminated GACA projects (36%) or
abandoned academic medicine altogether. Of respondents currently at GWEP sites
(43%), only 13% report a GWEP budget including GACA-like support. Those with GWEP
roles attributed their current standing to experience gained through GACA
funding. These consequences are alarming and represent a major setback to
academic geriatrics. GACA's singular contribution to the mission of geriatric
medicine must prompt vigorous efforts to restore it as a distinct funding
opportunity.
PMID- 28418067
TI - A case series of vital signs-controlled, patient-assisted intravenous analgesia
(VPIA) using remifentanil for labour and delivery.
AB - Intravenous remifentanil patient-controlled analgesia can be used during labour
as an alternative to epidural analgesia. Adverse effects of opioids, including
hypoxia and bradycardia, may lead to maternal morbidity and mortality. We devised
an interactive feedback system based on a clinical proportional algorithm, to
continuously monitor for adverse effects to enhance safety and better titrate
analgesia. This vital signs-controlled, patient-assisted intravenous analgesia
with remifentanil used a prototype delivery system linked to a pulse oximeter
that evaluated maternal oxygen saturation and heart rate continuously. With this
system, we detected oxygen saturation < 95% for more than 60 s in 15 of 29
subjects (52%); and heart rate < 60 min-1 for more than 60 s in 7 of 29 subjects
(24%) during use. The system automatically responded appropriately by reducing
the dosages and temporarily halting remifentanil administration, thus averting
further hypoxia and bradycardia.
PMID- 28418068
TI - Recombinant overexpression of dihydroneopterin aldolase catalyst potentially
regulates folate-biofortification.
AB - We aim to investigate the prospects of increased production of folate through the
overexpression of heterologous dihydroneopterin aldolase catalyst. The gene
encoding aldolase catalyst was cloned into an expression vector and the induced
recombinant protein was purified through metal-affinity chromatography which
appeared at 14 kDa position on polyacrylamide-gel. Remarkably, a periodic
increase in the extracellular and intracellular folic acid concentration was
observed at 4 h growth of induced recombinant DHNA samples than control in a pH
dependent manner. Maximum folate concentration was observed with at least twofold
increase in induced recombinant samples at pH8.0 compared to the significant
decline at 6 h growth. Consistently, heterologous overexpression of bacterial
aldolase through Agrobacterium-mediated genetic transformation of tobacco led to
more than 2.5-fold increase in the folate concentration in the transgenic leaves
than control tissues. These data are veritable inspecting metabolic flux in both
bacterial and plant systems, thus providing directions for future research on
folate agri-fortification.
PMID- 28418069
TI - Genetic control of plasticity of oil yield for combined abiotic stresses using a
joint approach of crop modelling and genome-wide association.
AB - Understanding the genetic basis of phenotypic plasticity is crucial for
predicting and managing climate change effects on wild plants and crops. Here, we
combined crop modelling and quantitative genetics to study the genetic control of
oil yield plasticity for multiple abiotic stresses in sunflower. First, we
developed stress indicators to characterize 14 environments for three abiotic
stresses (cold, drought and nitrogen) using the SUNFLO crop model and phenotypic
variations of three commercial varieties. The computed plant stress indicators
better explain yield variation than descriptors at the climatic or crop levels.
In those environments, we observed oil yield of 317 sunflower hybrids and
regressed it with three selected stress indicators. The slopes of cold stress
norm reaction were used as plasticity phenotypes in the following genome-wide
association study. Among the 65 534 tested Single Nucleotide Polymorphisms
(SNPs), we identified nine quantitative trait loci controlling oil yield
plasticity to cold stress. Associated single nucleotide polymorphisms are
localized in genes previously shown to be involved in cold stress responses:
oligopeptide transporters, lipid transfer protein, cystatin, alternative oxidase
or root development. This novel approach opens new perspectives to identify
genomic regions involved in genotype-by-environment interaction of a complex
traits to multiple stresses in realistic natural or agronomical conditions.
PMID- 28418070
TI - A signature of tree health? Shifts in the microbiome and the ecological drivers
of horse chestnut bleeding canker disease.
AB - Host susceptibility to pathogens can be shaped by genetic, ecological, and
evolutionary factors. The ability to predict the spread of disease therefore
requires an integrated understanding of these factors, including effects of pests
on pathogen growth and competition between pathogens and commensal microbiota for
host resources. We examined interactions between the leaf-mining moth Cameraria
ohridella, the bacterial causal agent of bleeding canker disease Pseudomonas
syringae pv aesculi, and the bark-associated microbiota of horse chestnut
(Aesculus hippocastanum) trees. Through surveys of > 900 trees from 60 sites in
the UK, we tested for ecological or life history predictors of leaf miner
infestation, bleeding canker, or coinfection. Using culture-independent
sequencing, we then compared the bark microbiomes from 46 trees to measure the
association between microbiome composition and key ecological variables,
including the severity of disease. Both pest and pathogen were found to respond
to tree characteristics, but neither explained damage inflicted by the other.
However, we found a clear loss of microbial diversity and associated shift in
microbiome composition of trees as a function of disease. These results show a
link between bark-associated microbiota and tree health that introduces the
intriguing possibility that tree microbiota play key roles in the spread of
disease.
PMID- 28418071
TI - Chronic exposure to graphene-based nanomaterials induces behavioral deficits and
neural damage in Caenorhabditis elegans.
AB - Nanomaterials of graphene and its derivatives have been widely applied in recent
years, but whose impacts on the environment and health are still not well
understood. In the present study, the potential adverse effects of graphite (G),
graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor
nervous system were investigated using nematode Caenorhabditis elegans as the
assay system. After being characterized using TEM, SEM, XPS and PLE, three
nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100
mg l-1 GO caused a significant reduction in the survival rate, but G and GDDs
showed low lethality on nematodes. After chronic exposure of sub-lethal dosages,
three nanomaterials were observed to distribute primarily in the pharynx and
intestine; but GQDs were widespread in nematode body. Three graphene-based
nanomaterials resulted in significant declines in locomotor frequency of body
bending, head thrashing and pharynx pumping. In addition, mean speed, bending
angle-frequency and wavelength of the crawling movement were significantly
reduced after exposure. Using transgenic nematodes, we found high concentrations
of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat
4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene
based nanomaterials can lead to damages in the dopaminergic and glutamatergic
neurons. The present data suggest that chronic exposure of graphene-based
nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and
neural damage. These findings provide useful information to understand the
toxicity and safe application of graphene-based nanomaterials. Copyright (c) 2017
John Wiley & Sons, Ltd.
PMID- 28418072
TI - MYB-GATA1 fusion promotes basophilic leukaemia: involvement of interleukin-33 and
nerve growth factor receptors.
AB - Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic
leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation
generating an MYB-GATA1 fusion gene in male infants with ABL. To better
understand its role, the chimeric MYB-GATA1 transcription factor was expressed in
CD34-positive haematopoietic progenitors, which were transplanted into
immunodeficient mice. Cells expressing MYB-GATA1 showed increased expression of
markers of immaturity (CD34), of granulocytic lineage (CD33 and CD117), and of
basophilic differentiation (CD203c and FcepsilonRI). UT-7 cells also showed
basophilic differentiation after MYB-GATA1 transfection. A transcriptomic study
identified nine genes deregulated by both MYB-GATA1 and basophilic
differentiation. Induction of three of these genes (CCL23, IL1RL1, and NTRK1) was
confirmed in MYB-GATA1-expressing CD34-positive cells by reverse transcription
quantitative polymerase chain reaction. Interleukin (IL)-33 and nerve growth
factor (NGF), the ligands of IL-1 receptor-like 1 (IL1RL1) and neurotrophic
receptor tyrosine kinase 1 (NTRK1), respectively, enhanced the basophilic
differentiation of MYB-GATA1-expressing UT-7 cells, thus demonstrating the
importance of this pathway in the basophilic differentiation of leukaemic cells
and CD34-positive primary cells. Finally, gene reporter assays confirmed that MYB
and MYB-GATA1 directly activated NTRK1 and IL1RL1 transcription, leading to
basophilic skewing of the blasts. MYB-GATA1 is more efficient than MYB, because
of better stability. Our results highlight the role of IL-33 and NGF receptors in
the basophilic differentiation of normal and leukaemic cells. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28418073
TI - Evolved changes in the intracellular distribution and physiology of muscle
mitochondria in high-altitude native deer mice.
AB - KEY POINTS: Mitochondrial function changes over time at high altitudes, but the
potential benefits of these changes for hypoxia resistance remains unclear. We
used high-altitude-adapted populations of deer mice, which exhibit enhanced
aerobic performance in hypoxia, to examine whether changes in mitochondrial
physiology or intracellular distribution in the muscle contribute to hypoxia
resistance. Permeabilized muscle fibres from the gastrocnemius muscle had higher
respiratory capacities in high-altitude mice than in low-altitude mice.
Highlanders also had higher mitochondrial volume densities, due entirely to an
enriched abundance of subsarcolemmal mitochondria, such that more mitochondria
were situated near the cell membrane and adjacent to capillaries. There were
several effects of hypoxia acclimation on mitochondrial function, some of which
were population specific, but they differed from the evolved changes in high
altitude natives, which probably provide a better indication of adaptive traits
that improve performance and hypoxia resistance at high altitudes. ABSTRACT: High
altitude natives that have evolved to live in hypoxic environments provide a
compelling system to understand how animals can overcome impairments in oxygen
availability. We examined whether these include changes in mitochondrial
physiology or intracellular distribution that contribute to hypoxia resistance in
high-altitude deer mice (Peromyscus maniculatus). Mice from populations native to
high and low altitudes were born and raised in captivity, and as adults were
acclimated to normoxia or hypobaric hypoxia (equivalent to 4300 m elevation). We
found that highlanders had higher respiratory capacities in the gastrocnemius
(but not soleus) muscle than lowlanders (assessed using permeabilized fibres with
single or multiple inputs to the electron transport system), due in large part to
higher mitochondrial volume densities in the gastrocnemius. The latter was
attributed to an increased abundance of subsarcolemmal (but not
intermyofibrillar) mitochondria, such that more mitochondria were situated near
the cell membrane and adjacent to capillaries. Hypoxia acclimation had no
significant effect on these population differences, but it did increase
mitochondrial cristae surface densities of mitochondria in both populations.
Hypoxia acclimation also altered the physiology of isolated mitochondria by
affecting respiratory capacities and cytochrome c oxidase activities in
population-specific manners. Chronic hypoxia decreased the release of reactive
oxygen species by isolated mitochondria in both populations. There were subtle
differences in O2 kinetics between populations, with highlanders exhibiting
increased mitochondrial O2 affinity or catalytic efficiency in some conditions.
Our results suggest that evolved changes in mitochondrial physiology in high
altitude natives are distinct from the effects of hypoxia acclimation, and
probably provide a better indication of adaptive traits that improve performance
and hypoxia resistance at high altitudes.
PMID- 28418074
TI - The effects of genome duplications in a community context.
AB - Contents 57 I. 57 II. 59 III. 59 IV. 63 V. 64 VI. 64 VII. 66 66 References 66
SUMMARY: Whole-genome duplication (WGD), or polyploidy, has important effects on
the genotype and phenotype of plants, potentially altering ecological
interactions with other organisms. Even though the connections between polyploidy
and species interactions have been recognized for some time, we are only just
beginning to test whether WGD affects community context. Here I review the sparse
information on polyploidy and community context and then present a set of
hypotheses for future work. Thus far, community-level studies of polyploids
suggest an array of outcomes, from no changes in community context to shifts in
the abundance and composition of interacting species. I propose a number of
mechanisms for how WGD could alter community context and how the emergence of
polyploids in populations could also alter the community context of parental
diploids and other plant species. Resolving how and when these changes are
expected to occur will require a deeper understanding of the connections among
WGD, phenotypic changes, and the direct and indirect effects of species
interactions.
PMID- 28418075
TI - Horizontal gene transfer is less frequent in eukaryotes than prokaryotes but can
be important (retrospective on DOI 10.1002/bies.201300095).
PMID- 28418076
TI - Ultrasonic modulation of tissue optical properties in ex vivo porcine skin to
improve transmitted transdermal laser intensity.
AB - BACKGROUND AND OBJECTIVE: Applications of light-based energy devices involving
optical targets within the dermis frequently experience negative side-effects
resultant from surface scattering and excess optical absorption by epidermal
melanin. As a broadband optical absorber, melanin decreases the efficacy of light
based treatments throughout the ultraviolet, visible, and near-infrared spectra
while also generating additional heat within the surface tissue that can lead to
inflammation or tissue damage. Consequently, procedures may be performed using
greater energy densities to ensure that the target receives a clinically relevant
dose of light; however, such practices are limited, as doing so tends to
exacerbate the detrimental complications resulting from melanin absorption of
treatment light. The technique presented herein represents an alternative method
of operation aimed at increasing epidermal energy fluence while mitigating excess
absorption by unintended chromophores. The approach involves the application of
continuously pulsed ultrasound to modulate the tissue's optical properties and
thereby improve light transmission through the epidermis. MATERIALS AND METHODS:
To demonstrate the change in optical properties, pulsed light at a wavelength of
532 nm from a Q-switched Nd:YAG laser was transmitted into 4 mm thick samples of
porcine skin, comprised of both epidermal and dermal tissue. The light was
transmitted using an optical waveguide, which allowed for an ultrasonic
transducer to be incorporated for simultaneous paraxial pulsation in parallel
with laser operation. Light transmitted through the tissue was measured by a
photodiode attached to an integrating sphere. RESULTS: Increasing the driving
voltage of ultrasonic pulsation resulted in an increase in mean transmitted
optical power of up to a factor of 1.742 +/- 0.0526 times the control, wherein no
ultrasound was applied, after which the optical power increase plateaued to an
average amplification factor of 1.733 +/- 0.549 times the control. CONCLUSIONS:
The increase implies a reduction in light either back-scattered or absorbed
within the tissue, which would allow for a greater proportion of incident energy
to be delivered to the clinical target, thereby improving procedural efficacy and
potentially reducing the severity of detrimental side-effects. Apparatus Lasers
Surg. Med. 49:666-674, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28418077
TI - Therapeutic protein deimmunization by T-cell epitope removal: antigen-specific
immune responses in vitro and in vivo.
AB - Hirudin III is an effective anti-coagulant; however, in 40% of treated patients,
a high-titer of anti-Hirudin III IgG antibodies is observed. Development of
antibody responses requires the activation of helper T lymphocyte (HTL), which is
dependent on peptide epitopes binding to HLA class II molecules. Based on
computational prediction softwares, four new mutants of Hirudin III, T4K, S9G,
V21G, and V21K, had been designed with the aim of reducing the binding affinity
of these HTL epitopes. The constructed mutants have been purified and assayed for
bioactivity. Finally in vitro and in vivo cell-mediated responses were assessed
and humoral immune assays were performed. All modified forms of Hirudin III were
active, and showed significantly reduced human T-cell responses. All mutants
indicated lower human IFN-gamma level compared to native Hirudin, and V21K
indicated lowest IFN-gamma level. Mice immunized with T4K and V21K showed a
significant reduction in total antibody responses and mouse IFN-gamma levels.
Mice immunized with V21K after 3rd immunization had lower T-cell proliferation
compared to native Hirudin and other mutants. Based on these results, V21K is
proposed as the best alternate Hirudin III candidate with lowest antigenicity.
These findings validate our rational design strategy aimed at providing new
active analogs of therapeutic proteins with reduced immunogenicity.
PMID- 28418078
TI - Induction of mitochondrial apoptotic pathway in triple negative breast carcinoma
cells by methylglyoxal via generation of reactive oxygen species.
AB - Triple negative breast cancer (TNBC) tends to form aggressive tumors associated
with high mortality and morbidity which urge the need for development of new
therapeutic strategies. Recently, the normal metabolite Methylglyoxal (MG) has
been documented for its anti-proliferative activity against human breast cancer.
However, the mode of action of MG against TNBC remains open to question. In our
study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC
cell lines and elucidated the underlying mechanisms. MG dose-dependently caused
cell death, induced apoptosis, and generated ROS in both the TNBC cell lines.
Furthermore, such effects were attenuated in presence of ROS scavenger N-Acetyl
cysteine. MG triggered mitochondrial cytochrome c release in the cytosol and up
regulated Bax while down-regulated anti-apoptotic protein Bcl-2. Additionally, MG
treatment down-regulated phospho-akt and inhibited the nuclear translocation of
the p65 subunit of NF-kappaB. MG exhibited a tumor suppressive effect in BALB/c
mouse 4T1 breast tumor model as well. The cytotoxic effect was studied using MTT
assay. Apoptosis, ROS generation, and mitochondrial dysfunction was evaluated by
flow cytometry as well as fluorescence microscopy. Western blot assay was
performed to analyze proteins responsible for apoptosis. This study demonstrated
MG as a potent anticancer agent against TNBC both in vitro and in vivo. The
findings will furnish fresh insights into the treatment of this subgroup of
breast cancer.
PMID- 28418079
TI - Loneliness and cardiovascular disease and the role of late-life depression.
AB - OBJECTIVE: Loneliness and depression have a strong reciprocal influence, and both
predict adverse health outcomes at old age. Therefore, this study examines
whether loneliness is associated with the presence of cardiovascular diseases
taking into account the role of late-life depression. METHODS: Cross-sectional
data of 477 older adults in the Netherlands Study of Depressed Older Persons were
used. Logistic regression analysis was performed to examine the relation between
loneliness and cardiovascular disease. Depression was added to the regression
model to examine whether depression is an explanatory factor in the association
between loneliness and cardiovascular disease. Interaction terms between
loneliness and depression and between loneliness and sex were introduced in the
regression model to investigate whether depressed and non-depressed participants,
and men and women differed in their association between loneliness and
cardiovascular disease. RESULTS: Of the overall group, 61% were lonely, 28% had a
history of cardiovascular disease and 74% were depressed. Loneliness and
cardiovascular disease were not associated in the overall group after adjustment
for confounders (continuous: odds ratio [OR] = 1.04, 95% confidence interval [CI]
= 0.98-1.10), p = 0.25; dichotomous: OR = 1.27, 95% CI = 0.80-2.03, p = 0.32).
For women, there was an association between loneliness and cardiovascular
diseases (continuous: OR = 1.13, 95% CI = 1.06-1.21, p < 0.001; dichotomous: OR =
2.64, 95% CI = 1.50-4.65, p = 0.001), but this association was not present in men
(OR = 0.96, 95% CI = 0.88-1.05, p = 0.38). This association remained significant
after adjustment for confounders, but it lost significance after adding
depression to the model. CONCLUSION: For women only, there was an association
between loneliness and cardiovascular disease. However, this association was
explained by depression, indicating that loneliness in its own right seems not
related with cardiovascular disease. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418080
TI - Phototoxic potential of undispersed and dispersed fresh and weathered Macondo
crude oils to Gulf of Mexico Marine Organisms.
AB - Crude oils contain a mixture of hydrocarbons, including phototoxic polycyclic
aromatic hydrocarbons (PAHs) that have the ability to absorb ultraviolet (UV)
light. Absorption of UV light by PAHs can substantially increase their toxicity
to marine organisms. The objective of the present study was to examine the
potential for phototoxicity of fresh and naturally weathered Macondo crude oils
alone and in combination with the dispersant Corexit 9500 to mysid shrimp
(Americamysis bahia), inland silverside (Menidia beryllina), sheepshead minnow
(Cyprinodon variegatus), and Gulf killifish (Fundulus grandis). Acute toxicity
tests were conducted using combinations of natural or artificial sunlight and low
energy water-accommodated fractions (WAFs) of fresh and weathered Macondo crude
oils collected from the Gulf of Mexico. Studies were also conducted to compare
the phototoxicity resulting from natural and artificial sunlight. Fresh Macondo
crude oil was more phototoxic than weathered crude oils, both in the presence and
in the absence of UV light. Differences in toxicity between fresh and weathered
crude oils were likely attributed to lighter-ringed PAHs in fresh crude oils.
Phototoxic PAHs were relatively resistant to weathering compared with lighter
ringed PAHs. The addition of Corexit 9500 to crude oil increased toxicity
compared with tests with crude oil alone, by increasing phototoxic PAH
concentrations in WAFs. Macondo crude oils had the potential to be phototoxic to
Gulf of Mexico marine organisms if specific light conditions and PAH
concentrations were present during the Deepwater Horizon oil spill. Environ
Toxicol Chem 2017;36:2640-2650. (c) 2017 SETAC.
PMID- 28418081
TI - Assessment of biofilm removal capacity of a broad host range bacteriophage JHP
against Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa is an efficient biofilm-dwelling microbial pathogen,
associated with nosocomial infections. These biofilm-associated infections are
resistant to antibiotics and immune defenses, therefore pose major problem
against their treatment. This scenario demands alternative therapeutic regimens,
and bacteriophage therapy is one among potential strategies for clinical
management of multiple drug resistance. In this investigation, the efficacy of a
bacteriophage, JHP, is evaluated to eradicate P. aeruginosa biofilms. Growth
kinetics of P. aeruginosa biofilm revealed that the highest cell density biofilm
(1.5 * 1016 CFU/mL) was established within the polystyrene microtiter plate at 72
h post inoculation. Pseudomonas aeruginosa biofilms of different ages, treated
with JHP (0.6 MOI) for different post-infection durations, reduced biomass from 2
to 4.5 logs (60-90%). JHP treatment before biofilm development reduced the
bacterial load up to 9 logs (>95% bacterial load reduction) as compared with
untreated control, which highlights its potential to prevent biofilm formation in
indwelling medical devices. Combinations of JHP with other phages or antibiotics
could be an efficient alternative for P. aeruginosa biofilm removal in clinical
and industrial settings.
PMID- 28418082
TI - Non-digestible carbohydrates supplementation increases miR-32 expression in the
healthy human colorectal epithelium: A randomized controlled trial.
AB - Colorectal cancer (CRC) risk is modulated by diet and there is convincing
evidence of reduced risk with higher non-digestible carbohydrates (NDCs)
consumption. Resistant starch (RS), a NDC, positively modulates the expression of
oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs
protect against CRC. The present study aimed to investigate the effects of
supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression
in the macroscopically-normal human rectal epithelium using samples from the DISC
Study, a randomized, double-blind, placebo-controlled dietary intervention. We
screened 1008 miRNAs in pooled post-intervention rectal mucosal samples from
participants allocated to the double placebo group and those supplemented with
both RS and PD. A total of 111 miRNAs were up- or down-regulated by at least
twofold in the RS + PD group compared with the control group. From these, eight
were selected for quantification in individual participant samples by qPCR, and
fold-change direction was consistent with the array for seven miRNAs. The
inconsistency for miR-133b and the lower fold-change values observed for the
seven miRNAs is probably because qPCR of individual participant samples is a more
robust and sensitive method of quantification than the array. miR-32 expression
was increased by approximately threefold (P = 0.033) in the rectal mucosa of
participants supplemented with RS + PD compared with placebo. miR-32 is involved
in the regulation of processes such as cell proliferation that are dysregulated
in CRC. Furthermore, miR-32 may affect non-canonical NF-kappaB signaling via
regulation of TRAF3 expression and consequently NIK stabilization.
PMID- 28418083
TI - Interannual variation in methane emissions from tropical wetlands triggered by
repeated El Nino Southern Oscillation.
AB - Methane (CH4 ) emissions from tropical wetlands contribute 60%-80% of global
natural wetland CH4 emissions. Decreased wetland CH4 emissions can act as a
negative feedback mechanism for future climate warming and vice versa. The impact
of the El Nino-Southern Oscillation (ENSO) on CH4 emissions from wetlands remains
poorly quantified at both regional and global scales, and El Nino events are
expected to become more severe based on climate models' projections. We use a
process-based model of global wetland CH4 emissions to investigate the impacts of
the ENSO on CH4 emissions in tropical wetlands for the period from 1950 to 2012.
The results show that CH4 emissions from tropical wetlands respond strongly to
repeated ENSO events, with negative anomalies occurring during El Nino periods
and with positive anomalies occurring during La Nina periods. An approximately 8
month time lag was detected between tropical wetland CH4 emissions and ENSO
events, which was caused by the combined time lag effects of ENSO events on
precipitation and temperature over tropical wetlands. The ENSO can explain 49% of
interannual variations for tropical wetland CH4 emissions. Furthermore, relative
to neutral years, changes in temperature have much stronger effects on tropical
wetland CH4 emissions than the changes in precipitation during ENSO periods. The
occurrence of several El Nino events contributed to a lower decadal mean growth
rate in atmospheric CH4 concentrations throughout the 1980s and 1990s and to
stable atmospheric CH4 concentrations from 1999 to 2006, resulting in negative
feedback to global warming.
PMID- 28418084
TI - Epstein-Barr virus infection induces genome-wide de novo DNA methylation in non
neoplastic gastric epithelial cells.
AB - Epstein-Barr virus (EBV)-positive gastric cancer (GC) shows a higher DNA
methylation epigenotype. EBV infection can causally induce genome-wide aberrant
DNA methylation, as previously demonstrated by in vitro infection experiments in
the low-methylation GC cell line MKN7. However, whether EBV exerts DNA
methylation remodelling properties in non-neoplastic epithelial cells remains
unclear. Here we performed post-infection time-series DNA methylation analyses
using the immortalized normal gastric epithelial cell line GES1. Genome-wide
analysis using Illumina's Infinium 450 k BeadArray demonstrated global de novo
DNA methylation from post-infection day 17, which was completed by 28 days in a
manner similar to that observed in MKN7 cells. De novo methylation of all types
of GC-specific methylation marker genes was observed, indicating that EBV
infection is sufficient for gastric epithelial cells to acquire an EBV-positive
GC epigenotype. Pyrosequencing demonstrated that methylation of the viral genome
preceded that of the host cellular genome, suggesting the existence of well
ordered mechanisms that induce methylation. Spatiotemporal representation with
differential models revealed dynamic alterations of DNA methylation in promoter
regions, occurring from lower-CpG peripheral regions and extending to higher-CpG
core regions. In summary, EBV infection exerted powerful pressure to induce
global de novo DNA methylation in non-neoplastic cells within a month in a
spatiotemporally well-ordered manner. Copyright (c) 2017 Pathological Society of
Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 28418086
TI - General dentists' use of diagnostic equipment and methods.
AB - An accurate diagnosis is essential for making treatment decisions in dentistry.
However, little research is available as to which tests are done routinely and
how commonly they are performed. The purpose of this study was to investigate
diagnostic methods and equipment used by general dentists in private practice in
Perth. The study involved a retrospective audit of 30 patient records from seven
individual general dentists working in private practices in the Perth
Metropolitan area. De-identification of patient records was done prior to the
researchers' visit. Radiographs were the most commonly used diagnostic tool.
Percussion was also commonly employed, followed by cold pulp testing and
mobility. The most commonly used tests were radiographs, percussion, periodontal
probing and visual examination. The frequency of these tests differed depending
on whether the patient presented with or without pain, with percussion and cold
tests used more frequently when the patient presented with pain.
PMID- 28418085
TI - Puquitinib, a novel orally available PI3Kdelta inhibitor, exhibits potent
antitumor efficacy against acute myeloid leukemia.
AB - The PI3Kdelta isoform (PIK3CD), also known as P110delta, is predominately
expressed in leukocytes and has been implicated as a potential target in the
treatment of hematological malignancies. In this report, we detailed the
pharmacologic properties of puquitinib, a novel, orally available PI3Kdelta
inhibitor. Puquitinib, which binds to the ATP-binding pocket of PI3Kdelta, was
highly selective and potent for PI3Kdelta relative to other PI3K isoforms and a
panel of protein kinases, exhibiting low-nanomolar biochemical and cellular
inhibitory potencies. Additional cellular profiling demonstrated that puquitinib
inhibited proliferation, induced G1 -phase cell-cycle arrest and apoptosis in
acute myeloid leukemia (AML) cell lines, through downregulation of PI3K
signaling. In in vivo AML xenografts, puquitinib alone showed stronger efficacy
than the well-known p110delta inhibitor, CAL-101, in association with a reduction
in AKT and ERK phosphorylation in tumor tissues, without causing noticeable
toxicity. Furthermore, the combination of puquitinib with cytotoxic drugs,
especially daunorubicin, yielded significantly stronger antitumor efficacy
compared with each agent alone. Thus, puquitinib is a promising agent with
pharmacologic properties that are favorable for the treatment of AML.
PMID- 28418087
TI - Traumatic stress-induced persistent changes in DNA methylation regulate
neuropeptide Y expression in rat jejunum.
AB - BACKGROUND: Stress-induced chronic neuropsychiatric conditions such as anxiety
are often co-morbid with gastrointestinal malfunctions. While we find enduring
anxiety-like symptoms following minimal traumatic brain injury (MTBI) in rats,
gastrointestinal consequences of MTBI remain elusive. METHODS: In this study, we
examined the effects of MTBI on a major gut peptide, neuropeptide Y (NPY) and gut
motility. DNA methylation was studied as a possible epigenetic mechanism
operative in the regulation of NPY expression in the gut. KEY RESULTS: Minimal
traumatic brain injury reduced the gut motility 48 hours and 30 days after
trauma. The expression of DNA methyltransferase isoforms (DNMT1, DNMT3a, and
DNMT3b) was altered in the jejunum 48 hours and 30 days after MTBI. However, the
mRNA levels of growth arrest and DNA damage 45 (GADD45) isoforms, GADD45a, and
GADD45b, which are believed to be involved in active DNA demethylation, initially
decreased at 48 hours but subsequently increased after 30 days of trauma.
Similarly, DNA hypomethylation at the NPY promoter region in the jejunum was
correlated with the increase in NPY mRNA and protein levels 30 days post-trauma.
On the other hand, DNA hypomethylation at 48 hours was associated with a decline
in NPY expression. Treatment with 5-azacytidine (5-AzaC), a DNMT inhibitor,
retarded DNA methylation and restored the NPY mRNA levels in the jejunum of MTBI
induced rats. CONCLUSIONS & INFERENCES: These results suggest that DNA
demethylation could be operative as an epigenetic mechanism in the long-term
regulation of NPY gene expression to alter the gut motility during traumatic
stress.
PMID- 28418088
TI - RACK1 forms a complex with FGFR1 and PKM2, and stimulates the growth and
migration of squamous lung cancer cells.
AB - Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth
factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as
well as cell growth in lung cancer. Better understanding the regulation of this
process would benefit the clinical treatment for lung cancer. Here, it has been
found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a
complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking
down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and
inhibited the growth and migration of lung cancer cells, while over-expression of
RACK1 in lung cancer cells led to the resistance to Erdafitinib. Moreover,
knocking down the expression of RACK1 impaired the tumorigenesis of lung cancer
driven by LKB loss and mutated Ras (KrasG12D). Taken together, our study
demonstrated the pivotal roles of RACK1 in FGFR1/PKM2 signaling, suggesting
FGFR1/RACK1/PKM2 might be a therapeutic target for lung cancer treatment.
PMID- 28418089
TI - Facts and values in psychotherapy-A critique of the empirical reduction of
psychotherapy within evidence-based practice.
AB - This paper addresses an implicit presupposition in research-supported
psychological treatments and evidence-based practice in psychology. It argues
that the notion of research-supported psychological treatments is based on a
reductive conceptualisation of psychotherapy. Research-supported psychological
treatments hinge upon an empirical reduction where psychotherapy schools become
conceptualized as mere collections of empirical propositions. However, this paper
argues that the different psychotherapy schools have distinct ethoses that are
constituted by normative claims. Consequently, the evaluation of the different
psychotherapy schools and the practice of psychotherapy should include the
underlying normative claims of these ethoses.
PMID- 28418091
TI - Newsworthiness vs scientific impact: are the most highly cited urology papers the
most widely disseminated in the media?
AB - OBJECTIVE: To assess whether a correlation exists between newsworthiness
(Altmetric score) and scientific impact markers, such as citation analysis,
impact factors, and levels of evidence. METHODS: The top five most cited articles
for the year 2014 and 2015 from the top 10 ranking urology journals (Scientific
Impact Group) were identified. The top 50 articles each in 2014 and 2015 were
identified from Altmetric support based on media activity (Media Impact Group).
We determined the number of citations that these articles received in the
scientific literature, and calculated correlations between citations with
Altmetric scores. RESULTS: In the Scientific Impact Group, the mean number of
citations per article was 37.6, and the most highly cited articles were oncology
guidelines. The mean Altmetric score in these articles was 14.8. There was a weak
positive correlation between citations and Altmetric score (rs = 0.35, 95%
confidence interval 0.16-0.52, P < 0.001). In the Media Impact Group, the mean
Altmetric score was 121.1 and most widely shared articles all related to sexual
medicine. In this group, the mean number of citations was 9.7 and there was a
weak negative correlation between Altmetric score and citations (rs = -0.20, P =
0.046). CONCLUSION: The top articles based on Altmetric scores were not highly
cited, suggesting that publications receiving the most media attention may not be
the most scientifically rigorous, or that this audience places greater value on
different subjects than the scientific community.
PMID- 28418090
TI - Natural mortality and cause of death analysis of the captive chimpanzee (Pan
troglodytes): A 35-year review.
AB - We present the spontaneous causes of mortality for 137 chimpanzees (Pan
troglodytes) over a 35-year period. A record review of the pathology database was
performed and a primary cause of mortality was determined for each chimpanzee.
The most common causes of mortality were as follows: cardiomyopathy (40% of all
mortalities), stillbirth/abortion, acute myocardial necrosis, chimpanzee-induced
trauma, amyloidosis, and pneumonia. Five morphologic diagnoses accounted for 61%
of mortalities: cardiomyopathy, hemorrhage, acute myocardial necrosis,
amyloidosis, and pneumonia. The most common etiologies were degenerative,
undetermined, bacterial, traumatic, and neoplastic. The cardiovascular system was
most frequently involved, followed by the gastrointestinal, respiratory, and
multisystemic diseases. Degenerative diseases were the primary etiological cause
of mortality of the adult captive chimpanzee population. Chimpanzee-induced
trauma was the major etiological cause of mortality among the perinatal and
infant population. This information should be a useful resource for veterinarians
and researchers working with chimpanzees.
PMID- 28418092
TI - Atmospheric chlorinated polyfluorinated ether sulfonate and ionic perfluoroalkyl
acids in 2006 to 2014 in Dalian, China.
AB - Chlorinated polyfluorinated ether sulfonate (Cl-PFESA; trade name F-53B) is an
alternative product for perfluorooctane sulfonate (PFOS) used in metal plating;
little is known about its levels in the environment and its risks. To our
knowledge, the present study constitutes the first report of Cl-PFESA in the
atmosphere. In 2006 to 2014, C8 Cl-PFESA, along with ionic perfluoroalkyl acids
(PFAAs), was detected in atmospheric particulate matter in Dalian, China.
Concentrations of C8 Cl-PFESA increased from 140 pg/m3 in 2007 to 722 pg/m3 in
2014. Levels of 11 (total) ionic PFAAs increased in 2006 to 2008 and decreased
afterward, with a range of 35.7 to 860 pg/m3 . The PFAAs in the particulate
matter were dominated by perfluorocarboxylates, with perfluorooctanoate detected
at the highest concentration at a mean level of 71.7 pg/m3 , followed by
perfluoroheptanoate and perfluorohexanoate. Perfluorosulfonates were detected at
lower levels, with mean concentrations of PFOS, perfluorobutanesulfonate, and
perfluorohexane sulfonate of 5.73, 1.64, and 1.24 pg/m3 , respectively. Back
trajectory analysis suggested that the air mass approaching Dalian during the
sampling originated from the northwest, where fluorochemical industry parks and
metal plating industries are densely located. No significant correlation was
observed between Cl-PFESA and the ionic PFAAs. The relatively high Cl-PFESA
concentrations suggested that it possibly contributed largely to the previously
reported exposure to undefined organic fluorine compounds, for which further
research on emission and environmental risks is needed. Environ Toxicol Chem
2017;36:2581-2586. (c) 2017 SETAC.
PMID- 28418094
TI - The skin microbiome of the common thresher shark (Alopias vulpinus) has low
taxonomic and gene function beta-diversity.
AB - The health of sharks, like all organisms, is linked to their microbiome. At the
skin interface, sharks have dermal denticles that protrude above the mucus, which
may affect the types of microbes that occur here. We characterized the microbiome
from the skin of the common thresher shark (Alopias vulpinus) to investigate the
structure and composition of the skin microbiome. On average 618 812 (80.9% +/-
S.D. 0.44%) reads per metagenomic library contained open reading frames; of
those, between 7.6% and 12.8% matched known protein sequences. Genera
distinguishing the A. vulpinus microbiome from the water column included,
Pseudoalteromonas (12.8% +/- 4.7 of sequences), Erythrobacter (5. 3% +/- 0.5) and
Idiomarina (4.2% +/- 1.2) and distinguishing gene pathways included, cobalt, zinc
and cadmium resistance (2.2% +/- 0.1); iron acquisition (1.2% +/- 0.1) and
ton/tol transport (1.3% +/- 0.08). Taxonomic community overlap (100 -
dissimilarity index) was greater in the skin microbiome (77.6), relative to the
water column microbiome (70.6) and a reference host-associated microbiome (algae:
71.5). We conclude the A. vulpinus skin microbiome is influenced by filtering
processes, including biochemical and biophysical components of the shark skin and
result in a structured microbiome.
PMID- 28418093
TI - Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but
enhances bone resorption activity via prolyl-4-hydroxylase 2.
AB - Osteogenic-angiogenic coupling is promoted by the hypoxia-inducible factor 1
alpha (HIF-1alpha) transcription factor, provoking interest in HIF activation as
a therapeutic strategy to improve osteoblast mineralization and treat
pathological osteolysis. However, HIF also enhances the bone-resorbing activity
of mature osteoclasts. It is therefore essential to determine the full effect(s)
of HIF on both the formation and the bone-resorbing function of osteoclasts in
order to understand how they might respond to such a strategy. Expression of HIF
1alpha mRNA and protein increased during osteoclast differentiation from CD14+
monocytic precursors, additionally inducing expression of the HIF-regulated
glycolytic enzymes. However, HIF-1alpha siRNA only moderately affected osteoclast
differentiation, accelerating fusion of precursor cells. HIF induction by
inhibition of the regulatory prolyl-4-hydroxylase (PHD) enzymes reduced
osteoclastogenesis, but was confirmed to enhance bone resorption by mature
osteoclasts. Phd2+/- murine osteoclasts also exhibited enhanced bone resorption,
associated with increased expression of resorption-associated Acp5, in comparison
with wild-type cells from littermate controls. Phd3-/- bone marrow precursors
displayed accelerated early fusion, mirroring results with HIF-1alpha siRNA. In
vivo, Phd2+/- and Phd3-/- mice exhibited reduced trabecular bone mass, associated
with reduced mineralization by Phd2+/- osteoblasts. These data indicate that HIF
predominantly functions as a regulator of osteoclast-mediated bone resorption,
with little effect on osteoclast differentiation. Inhibition of HIF might
therefore represent an alternative strategy to treat diseases characterized by
pathological levels of osteolysis. (c) 2017 The Authors. The Journal of Pathology
published by John Wiley & Sons Ltd on behalf of Pathological Society of Great
Britain and Ireland.
PMID- 28418096
TI - Expression of toll-like receptors in T lymphocytes stimulated with N-(3
oxododecanoyl)-L-homoserine lactone from Pseudomonas aeruginosa.
AB - The establishment of chronic Pseudomonas aeruginosa infections is correlated with
the disturbance of the host immune system. The P. aeruginosa quorum-sensing
molecule N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL) has the potential
to modulate the host immune system. The immune system recognizes pathogens via
toll-like receptors (TLRs). We found that 3-O-C12-HSL induced TLR changes in
monocytes. However, the role of T cells in P. aeruginosa infection has not been
delineated. In order to understand this activity, we examined whether 3-O-C12-HSL
has an effect on the immune function and the expression of TLRs in T lymphocytes.
Human peripheral blood mononuclear cells (PBMCs) cells were cultured with 0, 1,
10, 50, or 100 MUM 3-O-C12-HSL for 12 h. TLR2/TLR4 expression and T-lymphocyte
proliferation were increased in a dose-dependent manner, and 100 MUM 3-O-C12-HSL
significantly increased TLR2 expression. Moreover, tumor necrosis factor-alpha
production of these PBMCs was inhibited. To conclude, 3-O-C12-HSL can induce
lymphocyte cell proliferation. These findings provide a new perspective on our
understanding of the persistence of the chronic inflammation that accompanies P.
aeruginosa infection.
PMID- 28418095
TI - The nuclear orphan receptor NR4A1 regulates beta1-integrin expression in
pancreatic and colon cancer cells and can be targeted by NR4A1 antagonists.
AB - beta1-Integrin is highly expressed and is a negative prognostic factor for colon
and pancreatic cancer patients and the gene plays a functional role in cell
migration and invasion. In this study, we demonstrate that beta1-integrin
expression is regulated in pancreatic and colon cancer cells by the pro-oncogenic
orphan nuclear receptor 4A1 (NR4A1, Nur77, TR3) and knockdown of this receptor by
RNA interference decreases beta1-integrin protein and mRNA expression, alpha5
integrin, and also expression of beta1-integrin-dependent phosphorylation of FAK
(pFak). Knockdown of NR4A1 also decreased migration and fibronectin-induced
adhesion in pancreatic (Panc1, L3.6 pL, and MiaPaCa2) and colon (RKO and SW480)
cancer cells. 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methane (C-DIM)
compounds containing p-hydroxy (DIM-C-pPhOH) and p-carbomethoxy (DIM-C-pPhCO2 Me)
groups are NR4A1 ligands that act as antagonists for this receptor. Treatment of
pancreatic and colon cancer cells with DIM-C-pPhOH or DIM-C-pPhCO2 Me mimics the
effects of NR4A1 knockdown and decreases beta1-integrin expression, beta1
integrin regulated genes and responses including migration and adhesion. The
results demonstrate a novel method for targeting beta1-integrin in colon and
pancreatic cancer cells and indicate possible clinical applications for C
DIM/NR4A1 antagonists for pancreatic and colon cancer therapy.
PMID- 28418097
TI - Genome and epigenome of a novel marine Thaumarchaeota strain suggest viral
infection, phosphorothioation DNA modification and multiple restriction systems.
AB - Marine Thaumarchaeota are abundant ammonia-oxidizers but have few representative
laboratory-cultured strains. We report the cultivation of Candidatus
Nitrosomarinus catalina SPOT01, a novel strain that is less warm-temperature
tolerant than other cultivated Thaumarchaeota. Using metagenomic recruitment,
strain SPOT01 comprises a major portion of Thaumarchaeota (4-54%) in temperate
Pacific waters. Its complete 1.36 Mbp genome possesses several distinguishing
features: putative phosphorothioation (PT) DNA modification genes; a region
containing probable viral genes; and putative urea utilization genes. The PT
modification genes and an adjacent putative restriction enzyme (RE) operon likely
form a restriction modification (RM) system for defence from foreign DNA. PacBio
sequencing showed >98% methylation at two motifs, and inferred PT guanine
modification of 19% of possible TGCA sites. Metagenomic recruitment also reveals
the putative virus region and PT modification and RE genes are present in 18-26%,
9-14% and <1.5% of natural populations at 150 m with >=85% identity to strain
SPOT01. The presence of multiple probable RM systems in a highly streamlined
genome suggests a surprising importance for defence from foreign DNA for dilute
populations that infrequently encounter viruses or other cells. This new strain
provides new insights into the ecology, including viral interactions, of this
important group of marine microbes.
PMID- 28418098
TI - Stress and subsidy effects of seagrass wrack duration, frequency, and magnitude
on salt marsh community structure.
AB - Environmental perturbations can strongly affect community processes and ecosystem
functions by acting primarily as a subsidy that increases productivity, a stress
that decreases productivity, or both, with the predominant effect potentially
shifting from subsidy to stress as the overall intensity of the perturbation
increases. While perturbations are often considered along a single axis of
intensity, they consist of multiple components (e.g., magnitude, frequency, and
duration) that may not have equivalent stress and/or subsidy effects. Thus,
different combinations of perturbation components may elicit community and
ecosystem responses that differ in strength and/or direction (i.e., stress or
subsidy) even if they reflect a similar overall perturbation intensity. To assess
the independent and interactive effects of perturbation components, we
experimentally manipulated the magnitude, frequency, and duration of wrack
deposition, a common stress-subsidy in a variety of coastal systems. The effects
of wrack perturbation on salt marsh community and ecosystem properties were
assessed both in the short-term (at the end of a 12-week experimental
manipulation) and long-term (6 months after the end of the experiment). In the
short-term, plants and associated benthic invertebrates exhibited primarily
stress-based responses to wrack perturbation. The extent of these stress effects
on density of the dominant plant Spartina alterniflora, total plant percent
cover, invertebrate abundance, and sediment oxygen availability were largely
determined by perturbation duration. Yet, higher nitrogen content of Spartina,
which indicates a subsidy effect of wrack, was influenced primarily by
perturbation magnitude in the short-term. In the longer term, perturbation
magnitude determined the extent of both stress and subsidy effects of wrack
perturbation, with lower subordinate plant percent cover and snail density, and
higher Spartina nitrogen content in high wrack biomass treatments. However,
stress effects on the marsh community were generally less pronounced 6 months
after the wrack perturbation, indicating capacity for recovery. Our results
demonstrate that individual perturbation components can determine the degree to
which its effects on the community elicit primarily stress- and/or subsidy-based
responses. Further, the nature and extent of stress-subsidy effects can change
over time, depending on species' relative ability to tolerate and/or recover from
perturbation.
PMID- 28418099
TI - Influence of Divalent Counterions on the Dynamics in DNA as Probed by Using a
Minor-Groove Binder.
AB - DNA dynamics, to which water, counterions, and DNA motions contribute, is a topic
of considerable interest because it is closely related to the efficiency of
biological functions performed by it. Simulation studies and experiments suggest
that the counterion dynamics in DNA probed by a minor-groove binder are similar
for various monovalent counterions. To date, the influence on DNA dynamics of
higher-valence counterions, which are also present around DNA and are known to
bind more strongly to it than monovalent ions, has not been studied. Herein we
investigated DNA dynamics in the presence of Mg2+ and Ca2+ , chosen for their
relative abundance in cells, by using minor-groove binder 4',6-diamidino-2
phenylindole (DAPI) as a fluorescence probe. The dynamics, as measured from the
time-resolved fluorescence Stokes shifts of DAPI bound to calf thymus DNA on a
subpicosecond-to-nanosecond timescale, were found to be very similar in the
presence of both the divalent ions and Na+ ions. The observation is explained by
considering the screening of the electric field of the divalent ion by its
hydration shell, preferential binding of the ions to the phosphate groups, and
displacement of ions from the minor groove by DAPI due to the stronger binding
interaction of the latter. Furthermore, the similarity of our results in the
presence of Na+ to those reported for smaller oligonucleotides suggests that the
chain length of DNA does not influence the DNA dynamics.
PMID- 28418100
TI - A surprisingly big role for big K+ channels in retinal horizontal cells.
PMID- 28418101
TI - Effect of an electronic medication administration record application on patient
safety.
AB - RATIONALE, AIMS, AND OBJECTIVES: To evaluate the effect of an electronic
medication administration record (eMAR) application on the rate of medication
errors in medication administration recording (ME-MAR). METHODS: A before-and
after, quasiexperimental study was conducted in a university hospital that
implemented the eMAR application in March 2014. Data collection was conducted in
April 2012 (pre-) and June 2014 (post-) by two pharmacists. The ME-MARs were
analysed by the staff involved to identify their cause. The two pharmacists
independently classified the ME-MARs. In the case of disagreement, a research
team examined the ME-MARs and categorized them by consensus. Three
classifications were used: A classic medication error taxonomy and 2 technology
induced error taxonomies. RESULTS: The pharmacists analysed 2835 (pre-) and 2621
(post-) medication administration records (MAR), respectively. Overall, the ME
MAR rate decreased from 48.0% (pre-) to 36.9% (post-) (P < .05). The same types
of ME-MAR were observed in both phases except for "MAR with incomplete
information," which was not observed in the postimplementation phase. In both
phases, the most frequent ME-MAR was "MAR at the wrong time" (MAR before or after
medication administration) (31.6% vs 30.2%). The main cause of ME-MARs in both
phases was the failure to follow work procedures. The potential future risk of ME
MARs significantly decreased after the eMAR implementation (P < .05). All ME-MARs
were "use errors" because of human factors. New ME-MARs (1.24%; n = 12) were
observed in the postimplementation phase. CONCLUSION: Use of the eMAR application
significantly reduces the rate of ME-MAR and their potential risk. The main cause
of ME-MAR was the failure to follow work procedures.
PMID- 28418102
TI - Efficacy and safety of combinations of mirabegron and solifenacin compared with
monotherapy and placebo in patients with overactive bladder (SYNERGY study).
AB - OBJECTIVE: To evaluate the potential of solifenacin 5 mg combined with mirabegron
25 or 50 mg to deliver superior efficacy compared with monotherapy, with
acceptable tolerability, in the general overactive bladder (OAB) population with
urinary incontinence (UI). PATIENTS AND METHODS: After a 4-week placebo run-in,
patients aged >=18 years with wet OAB (urgency, urinary frequency and UI) for >=3
months who recorded on average >=8 micturitions/24 h, >=1 urgency episode/24 h,
and >=3 UI episodes over the 7-day micturition diary, were eligible for
randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg +
mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg
(combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg;
or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary
efficacy variables were change from baseline to end of treatment (EoT) in the
mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day
electronic micturition diary. Secondary efficacy variables included change from
baseline to EoT in the mean volume voided/micturition, change from baseline at
weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h,
urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h;
the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in
the last 7 days prior to each visit, micturition frequency normalisation (<8
episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and
nocturia episodes in the 7-day diary. Safety assessments included incidence and
frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR)
urine volume, and changes from baseline in laboratory parameters. RESULTS: Whilst
the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean
(standard error) adjusted difference of -0.20 (0.12) UI episodes/24 h (95%
confidence interval -0.44, 0.04, P = 0.033), there was no statistical superiority
vs mirabegron 50 mg [-0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary
analyses, all active treatment groups had greater improvements in UI episodes/24
h vs placebo, with effect sizes for the combined therapy groups (combined S5 +
M25 group: -0.70 episodes/24 h; combined S5 + M50 group: -0.65 episodes/24 h)
that were substantially higher than those obtained with monotherapy (range -0.37
episodes/24 h for mirabegron 25 mg to -0.45 episodes/24 h for solifenacin 5 mg).
For micturitions/24 h, adjusted change from baseline to EoT was greater in the
combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P
values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively;
combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and
mirabegron 25 mg, respectively). All active treatment groups had greater
improvements in the mean numbers of micturitions/24 h vs placebo, with effect
sizes for the combined therapy groups (combined S5 + M25 group: -0.85
micturitions/24 h; combined S5 + M50 group: -0.95 micturitions/24 h) higher than
with mirabegron monotherapy (25 mg: -0.36; 50 mg: -0.39 micturitions/24 h) and
solifenacin 5 mg (-0.56 micturitions/24 h). The combined S5 + M50 group was
statistically significantly superior to both monotherapies at EoT for UUI
episodes, urgency episodes and nocturia, with effect sizes that appeared to be
additive. The combined S5 + M25 group was statistically significantly superior to
mirabegron 25 mg for the same variables, except for nocturia. In responder
analyses at the EoT, odds ratios in favour of both combined therapies vs
monotherapies were shown for the proportion of patients with zero UI episodes and
those achieving micturition frequency normalisation. There was a slightly
increased frequency of TEAEs in the combined therapy groups vs monotherapies and
placebo. Most of the TEAEs were mild or moderate in severity. Events indicative
of urinary retention were reported slightly more frequently in the combined
therapy groups vs monotherapy and placebo. PVR volume was slightly increased in
the combined therapy groups vs solifenacin 5 mg, mirabegron monotherapy, and
placebo groups. There were slightly higher frequencies of dry mouth,
constipation, and dyspepsia in the combined therapy groups vs monotherapies.
There were no concerns regarding electrocardiograms and laboratory data.
CONCLUSION: In the largest OAB study to date, combined therapy with solifenacin 5
mg + mirabegron 25 mg and solifenacin 5 mg + mirabegron 50 mg provided consistent
improvements in efficacy compared with the respective monotherapies across most
of the outcome parameters, with effect sizes generally consistent with an
additive effect. Although the combined S5 + M50 group did not achieve a
statistically significant effect vs mirabegron 50 mg in the primary analysis of
one of the co-primary endpoints (change from baseline in mean number of UI
episodes/24 h), it approached statistical significance (P = 0.052), and the
nominal P values for the other co-primary endpoint (micturitions/24 h) were
<0.05. Most effects of combined therapy vs monotherapy were observable by week 4.
The clinical relevance of the improvements seen with combined therapy for several
objective OAB outcome measures was also supported by the improvements of combined
therapy vs monotherapy in the responder analyses.
PMID- 28418103
TI - Neurogenic and myogenic patterns of electrical activity in isolated intact mouse
colon.
AB - BACKGROUND: Relatively little is known about the electrical rhythmicity of the
whole colon, where long neural pathways are preserved. METHODS: Smooth muscle
electrical activity was recorded extracellularly from the serosa of isolated flat
sheet preparations consisting of the whole mouse colon (n=31). KEY RESULTS: Two
distinct electrical patterns were observed. The first, long intense spike bursts,
occurred every 349+/-256 seconds (0.2+/-0.2 cpm), firing action potentials for
31+/-11 seconds at 2.1+/-0.5 Hz. They were hexamethonium- and tetrodotoxin
sensitive, but persisted in nicardipine as 2 Hz electrical oscillations lacking
action potentials. This pattern is called here neurogenic spike bursts. The
second pattern, short spike bursts, occurred about every 30 seconds (2.0+/-0.6
cpm), with action potentials firing at about 1 Hz for 9 seconds (1.0+/-0.2 Hz,
9+/-4 seconds). Short spike bursts were hexamethonium- and tetrodotoxin-resistant
but nicardipine-sensitive and thus called here myogenic spike bursts. Neurogenic
spike bursts transiently delayed myogenic spike bursts, while blocking neurogenic
activity enhanced myogenic spike burst durations. External stimuli significantly
affected neurogenic but not myogenic spike bursts. Aboral electrical or
mechanical stimuli evoked premature neurogenic spike bursts. Circumferential
stretch significantly decreased intervals between neurogenic spike bursts.
Lesioning the colon down to 10 mm segments significantly increased intervals or
abolished neurogenic spike bursts, while myogenic spike bursts persisted.
CONCLUSIONS & INFERENCES: Distinct neurogenic and myogenic electrical patterns
were recorded from mouse colonic muscularis externa. Neurogenic spike bursts
likely correlate with neurogenic colonic migrating motor complexes (CMMC) and are
highly sensitive to mechanical stimuli. Myogenic spike bursts may correspond to
slow myogenic contractions, whose duration can be modulated by enteric neural
activity.
PMID- 28418104
TI - Is the nuclear refractive index lower than cytoplasm? Validation of phase
measurements and implications for light scattering technologies.
AB - The refractive index (RI) of biological materials is a fundamental parameter for
the optical characterization of living systems. Numerous light scattering
technologies are grounded in a quantitative knowledge of the refractive index at
cellular and subcellular scales. Recent work in quantitative phase microscopy
(QPM) has called into question the widely held assumption that the index of the
cell nucleus is greater than that of the cytoplasm, a result which disagrees with
much of the current literature. In this work, we critically examine the
measurement of the nuclear and whole-cell refractive index using QPM, validating
that nuclear refractive index is lower than that of cytoplasm in four diverse
cell lines and their corresponding isolated nuclei. We further examine Mie
scattering and phase-wrapping as potential sources of error in these
measurements, finding they have minimal impact. Finally, we use simulation to
examine the effects of incorrect RI assumptions on nuclear morphology
measurements using angle-resolved scattering information. Despite an erroneous
assumption of the nuclear refractive index, accurate measurement of nuclear
morphology was maintained, suggesting that light scattering modalities remain
effective.
PMID- 28418105
TI - Climate- and successional-related changes in functional composition of European
forests are strongly driven by tree mortality.
AB - Intense droughts combined with increased temperatures are one of the major
threats to forest persistence in the 21st century. Despite the direct impact of
climate change on forest growth and shifts in species abundance, the effect of
altered demography on changes in the composition of functional traits is not well
known. We sought to (1) quantify the recent changes in functional composition of
European forests; (2) identify the relative importance of climate change, mean
climate and forest development for changes in functional composition; and (3)
analyse the roles of tree mortality and growth underlying any functional changes
in different forest types. We quantified changes in functional composition from
the 1980s to the 2000s across Europe by two dimensions of functional trait
variation: the first dimension was mainly related to changes in leaf mass per
area and wood density (partially related to the trait differences between
angiosperms and gymnosperms), and the second dimension was related to changes in
maximum tree height. Our results indicate that climate change and mean climatic
effects strongly interacted with forest development and it was not possible to
completely disentangle their effects. Where recent climate change was not too
extreme, the patterns of functional change generally followed the expected
patterns under secondary succession (e.g. towards late-successional short
statured hardwoods in Mediterranean forests and taller gymnosperms in boreal
forests) and latitudinal gradients (e.g. larger proportion of gymnosperm-like
strategies at low water availability in forests formerly dominated by broad
leaved deciduous species). Recent climate change generally favoured the dominance
of angiosperm-like related traits under increased temperature and intense
droughts. Our results show functional composition changes over relatively short
time scales in European forests. These changes are largely determined by tree
mortality, which should be further investigated and modelled to adequately
predict the impacts of climate change on forest function.
PMID- 28418106
TI - Student-derived solutions to address barriers hindering reports of unprofessional
behaviour.
AB - BACKGROUND: Barriers hinder medical students from reporting breaches in
professional behaviour, which can adversely impact institutional culture. No
studies have reported student perspectives on how to address these barriers
successfully. Our study (i) evaluated the likelihood of reporting based on
violation severity, (ii) assessed barriers to reporting and (iii) elicited
students' proposed solutions. METHODS: Four medical students designed a cross
sectional study in 2015. In response to seven scenarios, students rated the
likelihood of reporting the violation, indicated perceived barriers and
identified solutions. Additional questions investigated the perceived importance
of professionalism, confidence in understanding professionalism and trust in
administrative protection from negative consequences. RESULTS: Two hundred and
seventy-two students in their clinical years (MS2-4) responded to the survey (RR
= 50%). Students were 70-90% likely to report major violations, but < 30% likely
to report minor or moderate violations. Barriers included concerns about an
uncomfortable relationship (41%), potential negative repercussions on grades or
opportunities (23%), and addressing by direct discussion rather than reporting
(23%). Solutions included simplified reporting, control over report release date,
improved feedback to reporters, training for real-time resolution of concerns and
a neutral resource to help students triage concerns. No differences existed
between classes regarding the importance or understanding of professionalism. In
linear regression, only importance of professionalism predicted likelihood of
reporting and this did not change with training. CONCLUSIONS: Hindered by common
barriers, students are unlikely to report a violation unless it is a serious
breach of professionalism. Student-derived solutions should be explored by
medical school administrators to encourage reporting of violation of
professionalism.
PMID- 28418107
TI - A new path in defining light parameters for hair growth: Discovery and modulation
of photoreceptors in human hair follicle.
AB - BACKGROUND AND OBJECTIVE: Though devices for hair growth based on low levels of
light have shown encouraging results, further improvements of their efficacy is
impeded by a lack of knowledge on the exact molecular targets that mediate
physiological response in skin and hair follicle. The aim of this study was to
investigate the expression of selected light-sensitive receptors in the human
hair follicle and to study the impact of UV-free blue light on hair growth ex
vivo. MATERIAL AND METHODS: The expression of Opsin receptors in human skin and
hair follicles has been characterized using RT-qPCR and immunofluorescence
approaches. The functional significance of Opsin 3 was assessed by silencing its
expression in the hair follicle cells followed by a transcriptomic profiling.
Proprietary LED-based devices emitting two discrete visible wavelengths were used
to access the effects of selected optical parameters on hair growth ex vivo and
outer root sheath cells in vitro. RESULTS: The expression of OPN2 (Rhodopsin) and
OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin
and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm
central wavelength significantly prolonged anagen phase in hair follicles ex vivo
that was correlated with sustained proliferation in the light-treated samples. In
contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did
not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair
follicle outer root sheath cells resulted in the altered expression of genes
involved in the control of proliferation and apoptosis, and abrogated stimulatory
effects of blue light (3.2 J/cm2 ; 453 nm) on proliferation in the outer root
sheath cells. CONCLUSIONS: We provide the first evidence that (i) OPN2 and OPN3
are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant
exposure exerts a positive effect on hair growth ex vivo, potentially via
interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28418108
TI - Metabolic characterization and transformation of the non-dairy Lactococcus lactis
strain KF147, for production of ethanol from xylose.
AB - The non-dairy lactic acid bacterium Lactococcus lactis KF147 can utilize xylose
as the sole energy source. To assess whether KF147 could serve as a platform
organism for converting second generation sugars into useful chemicals, the
authors characterized growth and product formation for KF147 when grown on
xylose. In a defined medium KF147 was found to co-metabolize xylose and arginine,
resulting in bi-phasic growth. Especially at low xylose concentrations, arginine
significantly improved growth rate. To facilitate further studies of the xylose
metabolism, the authors eliminated arginine catabolism by deleting the arcA gene
encoding the arginine deiminase. The fermentation product profile suggested two
routes for xylose degradation, the phosphoketolase pathway and the pentose
phosphate pathway. Inactivation of the phosphoketolase pathway redirected the
entire flux through the pentose phosphate pathway whereas over-expression of
phosphoketolase increased the flux through the phosphoketolase pathway. In
general, significant amounts of the mixed-acid products, including lactate,
formate, acetate and ethanol, were formed irrespective of xylose concentrations.
To demonstrate the potential of KF147 for converting xylose into useful chemicals
the authors chose to redirect metabolism towards ethanol production. A synthetic
promoter library was used to drive the expression of codon-optimized versions of
the Zymomonas mobilis genes encoding pyruvate decarboxylase and alcohol
dehydrogenase, and the outcome was a strain producing ethanol as the sole
fermentation product with a high yield corresponding to 83% of the theoretical
maximum. The results clearly indicate the great potential of using the more
metabolically diverse non-dairy L. lactis strains for bio-production based on
xylose containing feedstocks.
PMID- 28418110
TI - Identification of circulating miRNA involved in meat yield of Korean cattle.
AB - Cattle plays an important role in providing essential nutrients through meat
production. Thus, we focused on epigenetic factors associated with meat yield. To
investigate circulating miRNAs that are involved with meat yield and connect
biofluids and longissimus dorsi (LD) muscle in Korean cattle, we performed
analyses of the carcass characteristics, miRNA array, qPCR, and bioinformatics.
Carcass characteristics relative to the yield grade (YG) showed that the yield
index and rib eye area were the highest, whereas the backfat thickness was the
lowest for YG A (equal to high YG) cattle among the three YGs. miRNA array sorted
the circulating miRNAs that connect biofluids and LD muscle. miRNA qPCR showed
that miR-15a (r = 0.84), miR-26b (r = 0.91), and miR-29c (r = 0.92) had positive
relationships with biofluids and LD muscle. In YG A cattle, miR-26b was
considered to be a circulating miRNA connecting biofluids and LD muscle because
the target genes of miR-26b were more involved with myogenesis. Then, miR-26b
targeted genes, DIAPH3 and YOD1, were downregulated in YG A cattle. Our results
suggest that miR-15a, miR-26b, and miR-29c are upregulated in biofluids and LD
muscle, whereas DIAPH3 and YOD1 are downregulated in the LD muscle of finishing
cattle steers.
PMID- 28418109
TI - Sagittal crest formation in great apes and gibbons.
AB - The frequency of sagittal crest expression and patterns of sagittal crest growth
and development have been documented in hominoids, including some extinct hominin
taxa, and the more frequent expression of the sagittal crest in males has been
traditionally linked with the need for larger-bodied individuals to have enough
attachment area for the temporalis muscle. In the present study, we investigate
sagittal cresting in a dentally mature sample of four hominoid taxa (Pan
troglodytes schweinfurthii, Gorilla gorilla gorilla, Pongo pygmaeus pygmaeus and
Hylobates lar). We investigate whether sagittal crest size increases with age
beyond dental maturity in males and females of G. g. gorilla and Po. pyg.
pygmaeus, and whether these taxa show sex differences in the timing of sagittal
crest development. We evaluate the hypothesis that the larger sagittal crest of
males may not be solely due to the requirement for a larger surface area than the
un-crested cranial vault can provide for the attachment of the temporalis muscle,
and present data on sex differences in temporalis muscle attachment area and
sagittal crest size relative to cranial size. Gorilla g. gorilla and Po. pyg.
pygmaeus males show significant relationships between tooth wear rank and
sagittal crest size, and they show sagittal crest size differences between age
groups that are not found in females. The sagittal crest emerges in early
adulthood in the majority of G. g. gorilla males, whereas the percentage of G. g.
gorilla females possessing a sagittal crest increases more gradually. Pongo pyg.
pygmaeus males experience a three-fold increase in the number of specimens
exhibiting a sagittal crest in mid-adulthood, consistent with a secondary growth
spurt. Gorilla g. gorilla and Po. pyg. pygmaeus show significant sex differences
in the size of the temporalis muscle attachment area, relative to cranial size,
with males of both taxa showing positive allometry not shown in females. Gorilla
g. gorilla males also show positive allometry for sagittal crest size relative to
cranial size. Our results suggest that although patterns of sagittal crest
expression have limited utility for taxonomy and phylogeny reconstruction, they
could be useful for reconstructing aspects of social behaviour in some extinct
hominin taxa. In particular, our results in G. g. gorilla and Po. pyg. pygmaeus,
which suggest that the size of sagittal crests in males cannot be solely
explained by the surface area required for attachment of the temporalis muscle,
offer partial support for the hypothesis that large sagittal crests form in
response to sexual selection and may play a role in social signalling.
PMID- 28418111
TI - Toward the Dark Matter of Natural Products.
AB - Considering the dynamic features of natural products, our access toward exploring
the entire diversity of natural products has been quite limited. It is
challenging to assess the diversity of natural products by using conventional
analytical methods, even with tandem chromatographic techniques, such as LC-MS
and GC-MS. This viewpoint is supported by the sequencing analyses of microbial
genomes, which have unveiled the potential of secondary metabolite production far
exceeding the number of isolated molecules. Recent advancements in metabolomics,
in concert with genomics analyses, have further extended the natural product
diversity, prompting growing awareness of the existence of reactive or short
lived natural molecules. This personal account introduces some examples of the
discoveries of hitherto elusive natural products, due to physico-chemical or
biological reasons, and highlights the significance of the dark matter of natural
products.
PMID- 28418112
TI - Photoresponsive Passive Micromixers Based on Spiropyran Size-Tunable Hydrogels.
AB - Microfluidic devices allow the manipulation of fluids down to the micrometer
scale and are receiving a lot of attention for applications where low volumes and
high throughputs are required. In these micro channels, laminar flow usually
dominates, which requires long residence times of the fluids, limiting the flow
speed and throughput. Here a switchable passive mixer has been developed to
control mixing and to easily clean microchannels. The mixer is based on a
photoresponsive spiropyran based hydrogel of which the dimensions can be tuned by
changing the intensity of the light. The size-tunable gels have been used to
fabricate a passive slanted groove mixer that can be switched off by light
allowing to change mixing of microfluidics to non-mixed flows. These findings
open new possibilities for multi-purpose microfluidic devices where mixers and
valves can be tuned by light.
PMID- 28418113
TI - Autochthonous Chagas disease in the southern United States: A case report of
suspected residential and military exposures.
AB - Chagas disease is a parasitic infection that can result in a progressive dilated
cardiomyopathy. Here, we present the epidemiologic details of a suspected locally
acquired transmission case originating from the southern United States. This is
the first published report of Chagas disease in a young, healthy United States
veteran with repeat triatomine exposures in Arizona. Military personnel and
Arizona residents should be aware of their Chagas disease transmission risks.
PMID- 28418114
TI - Hearing at speech frequencies is different from what we thought.
PMID- 28418116
TI - "What is the point of life?": An interpretative phenomenological analysis of
suicide in young menwith first-episode psychosis.
AB - BACKGROUND: Lifetime risk of suicide in first-episode psychosis far exceeds the
general population, with the risk of suicide persisting long after first
presentation. There is strong evidence to suggest that women more frequently
attempt suicide, while men are at a greater risk of completing suicide. First
hand experiential evidence is needed in order to better understand men's motives
for, and struggles with, suicidality in early psychosis. METHODS: Semi-structured
interviews were conducted with 7 participants. The interviews explored each
respondent's account of their suicide attempt within the broader context of their
life, in relation to their past, present and future. In line with the
exploratory, inductive nature of the study, an Interpretative Phenomenological
Analysis was used to explore the meaning of suicide attempts in these accounts.
RESULTS: Three super-ordinate themes emerged: Self-as-vulnerable (intra- and
inter-personal relationships), appraisal of cumulative life events as unbearable
and meaning of recovery marked by shared sense of hope and imagery for the
future. CONCLUSIONS: Young men in the early stages of their treatment are seeking
to find meaning for frightening, intrusive experiences with origins which often
precede psychosis. These experiences permeate personal identity, relationships
and recovery. Suicide was perceived as an escape from this conundrum, and was
pursued angrily and impulsively. By contrast, the attainment of hope was marked
by sharing one's burden and finding a sense of belonging. Specialized assertive
outreach programmes may be beneficial in improving the social inclusion of young
men who may be particularly marginalized.
PMID- 28418115
TI - Aggravation of diabetes, and incompletely deficient insulin secretion in a case
with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with
nivolumab.
AB - Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse
effects, especially in the endocrine system. Several cases of acute-onset insulin
dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of
these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1
diabetes, possibly suggesting that HLA might be involved in the onset of diabetes
with anti-PD-1 therapy. We describe an atypical case of hyperglycemia after anti
PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes
and steroid diabetes was given nivolumab three times for chemoresistant
adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he
had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without
ketosis and with incompletely deficient insulin secretion. The patient had both
type 1 diabetes susceptible (HLA-A*24:02 and -DRB1*09:01) and resistant (HLA
DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously
reported in anti-PD-1 antibody-induced diabetes, and might have influenced the
preservation of insulin secretion after nivolumab administration in the present
case.
PMID- 28418117
TI - Articulating the ideal: 50 years of interprofessional collaboration in Medical
Education.
AB - CONTEXT: Health care delivery and the education of clinicians have changed
immensely since the creation of the journal Medical Education. In this project,
we seek to answer the following three questions: How has the concept of
collaboration changed over the past 50 years in Medical Education? Have the
participants involved in collaboration shifted over time? Has the idea of
collaboration itself been transformed over the past 50 years? METHODS: Starting
from a constructionist view of scientific discourse, we used directed content
analysis to sample, code and analyse 144 collaboration-related articles over the
50-year life span of Medical Education. We developed an analytical framework to
identify the key components of varying articulations of 'collaboration', with a
focus on shifts in language and terminology over time. Our sample was drawn from
an archive of 1221 articles developed to celebrate the 50th anniversary of
Medical Education. RESULTS: Interprofessional collaboration is conceptualised in
three primary ways throughout our sample: as a psychometric property; as tasks or
activities, and, more recently, as 'togetherness'. The first conceptualisation
articulates collaboration as involving knowledge or skills that are teachable to
individuals, the second as involving the education of teams to engage in
structured meetings or task distribution, and the third as the building of
networks of individuals who learn to form team identities. The 'leader' of
collaboration is typically conceptualised as the doctor, who is consistently
articulated by authors as the active agent of collaborative care. Other
clinicians and students of other professions are, as the wording in this sentence
suggests, usually positioned as 'others', and thus as more passive participants
in, or even observers of, 'collaboration'. CONCLUSIONS: In order to meet goals of
meaningful collaboration leading to higher-quality care, it behoves us as a
community of educators and researchers to heed the ways in which we teach, think
and write about interprofessional collaboration, interrogating our own language
and assumptions that may be betraying and reproducing harmful care hierarchies.
PMID- 28418118
TI - Enantioselective Heck-Matsuda Arylations through Chiral Anion Phase-Transfer of
Aryl Diazonium Salts.
AB - A mild, asymmetric Heck-Matsuda reaction of five-, six- and seven-membered ring
alkenes and aryl diazonium salts is presented. High yields and
enantioselectivities were achieved using Pd0 and chiral anion co-catalysts, the
latter functioning as a chiral anion phase-transfer (CAPT) reagent. For certain
substrate classes, the chiral anion catalysts were modulated to minimize the
formation of undesired by-products. More specifically, BINAM-derived phosphoric
acid catalysts were shown to prevent alkene isomerization in cyclopentene and
cycloheptene starting materials. DFT(B3LYP-D3) computations revealed that
increased product selectivity resulted from a chiral anion dependent lowering of
the activation barrier for the desired pathway.
PMID- 28418120
TI - Catalytic Enantioselective Synthesis of 2,5-Dihydrooxepines.
AB - A Michael addition initiated cyclopropanation/retro-Claisen rearrangement tandem
reaction was developed for the enantioselective synthesis of highly
functionalized 2,5-dihydrooxepines. In the presence of a chiral oxazaborolidinium
ion (COBI) catalyst, the reaction proceeds to give good yields and high
enantioselectivity.
PMID- 28418119
TI - Endoplasmic reticulum stress pathway PERK-eIF2alpha confers radioresistance in
oropharyngeal carcinoma by activating NF-kappaB.
AB - Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis
and development of malignant tumors, as well as in the regulation of
radiochemoresistance and chemoresistance in many malignancies. ERS signaling
pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic
initiation factor-2 (eIF2alpha) may induce aberrant activation of nuclear factor
kappaB (NF-kappaB). Our previous study showed that NF-kappaB conferred
radioresistance in lymphoma cells. However, whether PERK-eIF2alpha regulates
radioresistance in oropharyngeal carcinoma through NF-kappaB activation is
unknown. Herein, we showed that PERK overexpression correlated with a poor
prognosis for patients with oropharyngeal carcinoma (P < 0.01). Meanwhile, the
percentage of the high expression level of PERK in oropharyngeal carcinoma
patients resistant to radiation was higher than in patients sensitive to
radiation (77.7 and 33.3%, respectively; P < 0.05). Silencing PERK and eIF2alpha
increased the radiosensitivity in oropharyngeal carcinoma cells and increased
radiation-induced apoptosis and G2/M phase arrest. PERK-eIF2alpha silencing also
inhibited radiation-induced NF-kappaB phosphorylation and increased the DNA
double strand break-related proteins ATM phosphorylation. NF-kappaB activator TNF
alpha and the ATM inhibitor Ku55933 offset the regulatory effect of eIF2alpha on
the expression of radiation-induced cell apoptosis-related proteins and the G2/M
phase arrest-related proteins. These data indicate that PERK regulates
radioresistance in oropharyngeal carcinoma through NF-kB activation-mediated
phosphorylation of eIF2alpha, enhancing X-ray-induced activation of DNA DSB
repair, cell apoptosis inhibition and G2/M cell cycle arrest.
PMID- 28418121
TI - The challenge of skin surveillance: observe or biopsy?
PMID- 28418122
TI - The heart of the problem.
PMID- 28418123
TI - Image Gallery: Nicolau syndrome after misuse of buprenorphine.
PMID- 28418124
TI - Image Gallery: Xanthoma tuberosum.
PMID- 28418125
TI - Quantitative risk assessment and the burden of fragrance contact allergy.
PMID- 28418126
TI - Evidence for a biofilm-based treatment strategy in the management of chronic
hidradenitis suppurativa.
PMID- 28418127
TI - Image Gallery: Subcutaneous fat necrosis of the newborn.
PMID- 28418128
TI - Better definition of hidradenitis suppurativa subtypes is needed to progress
disease-specific treatment outcomes.
PMID- 28418129
TI - Ichthyoses: new insights unravel defects in skin barrier function resulting in
diverse clinical and morphological phenotypes.
PMID- 28418130
TI - Image Gallery: Pemphigoid gestationis mimicking a gyrate erythema.
PMID- 28418131
TI - Measuring quality of life in infants, children and adolescents with eczema.
PMID- 28418132
TI - Image Gallery: Immunocompromised patient presenting with inguinal rash: a case of
Scedosporium apiospermum.
PMID- 28418133
TI - Deferoxamine: potential novel topical therapeutic for chronic wounds.
PMID- 28418134
TI - The four Ws of skin cancer surveillance in patients with melanoma: Why? Who?
When? Where?
PMID- 28418135
TI - Cover Image: Are melanocyte-associated peptides the elusive autoantigens in
alopecia areata?
PMID- 28418136
TI - Five-year efficacy of biologics for psoriasis in the real world of daily
practice.
PMID- 28418137
TI - Pregnancy and fetal outcomes after paternal exposure to azathioprine,
methotrexate or mycophenolic acid: a critically appraised topic.
PMID- 28418138
TI - Finding a HOME for outcome measures in atopic dermatitis.
PMID- 28418140
TI - Shedding light on drug photosensitivity reactions.
PMID- 28418141
TI - Image Gallery: Verrucous porokeratosis with characteristic histopathological and
dermoscopic features.
PMID- 28418142
TI - The global burden of diabetic wounds.
PMID- 28418143
TI - Evidence-based medicine for atopic eczema: identifying the knowns and unknowns.
PMID- 28418144
TI - Hand eczema is to be taken seriously ....
PMID- 28418145
TI - Dermatological evaluation in patients with skin of colour: the effect of erythema
on outcome measures in atopic dermatitis.
PMID- 28418149
TI - Image Gallery: Dermoscopy for hair casts due to traction.
PMID- 28418151
TI - Health-related quality of life in hidradenitis suppurativa.
PMID- 28418152
TI - Paternal drug exposure: plenty of confounders, few conclusions.
PMID- 28418153
TI - Image Gallery: A rare abscess-like presentation of Langerhans cell histiocytosis.
PMID- 28418154
TI - Can positron emission tomography (PET) unravel the link between adipose tissue,
vascular inflammation and cardiovascular risk in patients with psoriasis?
PMID- 28418155
TI - Meeting the psychological needs of dermatology patients.
PMID- 28418156
TI - Cutaneous lymphomas in childhood and adolescence: much needed new data.
PMID- 28418157
TI - Effect of canal preparation with TRUShape and Vortex rotary instruments on three
dimensional geometry of oval root canals.
AB - The purpose of this study was to assess the geometry of non-round root canals
after preparation with TRUShape (a novel instrument with s-shaped longitudinal
design) in comparison to conventional rotary instrumentation using micro-computed
tomography. Twenty distal root canals of mandibular molars were randomly
distributed in two groups to be shaped with either TRUShape or Vortex rotaries.
Percentages of unprepared surface and volume of dentin removal for the entire
canal and for the apical 4 mm were calculated. Canal transportation and the
structure model index (SMI) were assessed. Data were compared with Student t
tests. Shaping with both techniques resulted in similar prepared surface and
volume of dentin removed, as well as the extent of canal transportation. The SMI
shape factor was significantly lower for TRUShape preparations (P = 0.04)
suggesting less rounding during rotary preparation. Although both instruments
were suitable for the preparation of oval canals, TRUShape appeared to better
conform to the original ribbon-shaped anatomy.
PMID- 28418158
TI - The phenology of leaf quality and its within-canopy variation is essential for
accurate modeling of photosynthesis in tropical evergreen forests.
AB - Leaf quantity (i.e., canopy leaf area index, LAI), quality (i.e., per-area
photosynthetic capacity), and longevity all influence the photosynthetic
seasonality of tropical evergreen forests. However, these components of tropical
leaf phenology are poorly represented in most terrestrial biosphere models
(TBMs). Here, we explored alternative options for the representation of leaf
phenology effects in TBMs that employ the Farquahar, von Caemmerer & Berry (FvCB)
representation of CO2 assimilation. We developed a two-fraction leaf (sun and
shade), two-layer canopy (upper and lower) photosynthesis model to evaluate
different modeling approaches and assessed three components of phenological
variations (i.e., leaf quantity, quality, and within-canopy variation in leaf
longevity). Our model was driven by the prescribed seasonality of leaf quantity
and quality derived from ground-based measurements within an Amazonian evergreen
forest. Modeled photosynthetic seasonality was not sensitive to leaf quantity,
but was highly sensitive to leaf quality and its vertical distribution within the
canopy, with markedly more sensitivity to upper canopy leaf quality. This is
because light absorption in tropical canopies is near maximal for the entire
year, implying that seasonal changes in LAI have little impact on total canopy
light absorption; and because leaf quality has a greater effect on photosynthesis
of sunlit leaves than light limited, shade leaves and sunlit foliage are more
abundant in the upper canopy. Our two-fraction leaf, two-layer canopy model,
which accounted for all three phenological components, was able to simulate
photosynthetic seasonality, explaining ~90% of the average seasonal variation in
eddy covariance-derived CO2 assimilation. This work identifies a parsimonious
approach for representing tropical evergreen forest photosynthetic seasonality in
TBMs that utilize the FvCB model of CO2 assimilation and highlights the
importance of incorporating more realistic phenological mechanisms in models that
seek to improve the projection of future carbon dynamics in tropical evergreen
forests.
PMID- 28418159
TI - Toxicity of sediment-associated substituted phenylamine antioxidants on the early
life stages of Pimephales promelas and a characterization of effects on
freshwater organisms.
AB - Substituted phenylamine antioxidants (SPAs) are high production volume chemicals
that are incorporated into a variety of commercial products (e.g., polymers,
dyes, lubricants). There are few data on chronic toxicity of SPAs to fish and no
data on the toxicity of SPAs to the early life stages of fish. The
physicochemical properties of SPAs would suggest that if they were to enter an
aquatic ecosystem they would partition into sediment. Therefore, the present
study focused on investigating the chronic effect of sediment-associated SPAs to
the early life stages of the fathead minnow (Pimephales promelas). Eggs and
larvae were exposed to sediment spiked with diphenylamine (DPA), N-phenyl-1
napthylamine (PNA), N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA),
or 4,4'-methylene-bis[N-sec-butylaniline] (MBA). The most sensitive endpoint for
DPA, PNA, and DPPDA was total survival with 21-d median lethal concentrations
(LC50s) based on concentration in overlying water of 1920, 74, and 35 MUg/L,
respectively. The most sensitive endpoint for MBA was growth with a 21-d median
effective concentration (EC50) of 71 MUg/L. The same endpoints were the most
sensitive in terms of concentrations of DPA, PNA, DPPDA, and MBA in sediment
(101, 54, 111, and 76 MUg/g dry wt, respectively). Species sensitivity
distributions (SSDs) were constructed for each SPA based on acute and chronic
toxicity data generated in the present study and found in the literature.
Overall, P. promelas was in the midrange of chronic sensitivity, with the most
sensitive species being Tubifex tubifex. The SSDs indicate that DPA based on
concentration in water is the least toxic to aquatic biota of the 4 SPAs
investigated. The constructed SSDs indicate that a concentration in water and
sediment of 1 MUg/L and 1 MUg/g dry weight, respectively, would be protective of
>95% of the aquatic species tested. Environ Toxicol Chem 2017;36:2730-2738. (c)
2017 SETAC.
PMID- 28418160
TI - Synthesis and Evaluation of 5-(o-Tolyl)-1H-tetrazole Derivatives as Potent
Anticonvulsant Agents.
AB - A series of 5-(o-tolyl)-1H-tetrazole derivatives were synthesized and evaluated
for their anticonvulsant activities. 1-(2-Methylbenzyl)-5-(o-tolyl)-1H-tetrazole
(3h) showed important anticonvulsant activity against the MES-induced seizures,
as well as lower neurotoxicity with an ED50 value of 12.7 mg/kg and a TD50 value
of over 500 mg/kg after intraperitoneal injection into mice, providing 3h with a
high protective index (TD50 /ED50 ) of over 39.4. The achieved results prove that
the distinctive compounds could be valuable as a model for future development,
adaptation, and investigation to construct more active analogues.
PMID- 28418161
TI - Explaining the apparent paradox of persistent selection for early flowering.
AB - Decades of observation in natural plant populations have revealed pervasive
phenotypic selection for early flowering onset. This consistent pattern seems at
odds with life-history theory, which predicts stabilizing selection on age and
size at reproduction. Why is selection for later flowering rare? Moreover,
extensive evidence demonstrates that flowering time can and does evolve. What
maintains ongoing directional selection for early flowering? Several non-mutually
exclusive processes can help to reconcile the apparent paradox of selection for
early flowering. We outline four: selection through other fitness components may
counter observed fecundity selection for early flowering; asymmetry in the
flowering-time-fitness function may make selection for later flowering hard to
detect; flowering time and fitness may be condition-dependent; and selection on
flowering duration is largely unaccounted for. In this Viewpoint, we develop
these four mechanisms, and highlight areas where further study will improve our
understanding of flowering-time evolution.
PMID- 28418162
TI - Exploring the institutional logics of health professions education scholarship
units.
AB - CONTEXT: Although health professions education scholarship units (HPESUs) share a
commitment to the production and dissemination of rigorous educational practices
and research, they are situated in many different contexts and have a wide range
of structures and functions. OBJECTIVES: In this study, the authors explore the
institutional logics common across HPESUs, and how these logics influence the
organisation and activities of HPESUs. METHODS: The authors analysed interviews
with HPESU leaders in Canada (n = 12), Australia (n = 21), New Zealand (n = 3)
and the USA (n = 11). Using an iterative process, they engaged in inductive and
deductive analyses to identify institutional logics across all participating
HPESUs. They explored the contextual factors that influence how these
institutional logics impact each HPESU's structure and function. RESULTS:
Participants identified three institutional logics influencing the organisational
structure and functions of an HPESU: (i) the logic of financial accountability;
(ii) the logic of a cohesive education continuum, and (iii) the logic of academic
research, service and teaching. Although most HPESUs embodied all three logics,
the power of the logics varied among units. The relative power of each logic
influenced leaders' decisions about how members of the unit allocate their time,
and what kinds of scholarly contribution and product are valued by the HPESU.
CONCLUSIONS: Identifying the configuration of these three logics within and
across HPESUs provides insights into the reasons why individual units are
structured and function in particular ways. Having a common language in which to
discuss these logics can enhance transparency, facilitate evaluation, and help
leaders select appropriate indicators of HPESU success.
PMID- 28418163
TI - Psychometric properties of the apathy evaluation scale in patients with
Parkinson's disease.
AB - Parkinson's disease (PD) frequently entails non-motor symptoms, worsening the
course of the disease. Apathy is one of the core neuropsychiatric symptoms that
has been investigated in recent years; research is however hampered by the
limited availability of well-evaluated apathy scales for these patients. We
evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a
sample of PD patients. Psychometric properties, convergent and discriminant
validity and sensitivity/specificity were evaluated in patients with (n = 582) or
without dementia/depression (n = 339). Internal consistency was high in the
entire sample as well as in patients without dementia/depression. Correlations
were moderate for convergent validity (UPDRS I item 4: motivation). While apathy
could be differentiated from cognitive decline, it was related to depression
(Geriatric Depression Scale, GDS-15). The overall classification accuracy based
on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits
good psychometric properties in PD patients with and without dementia and/or
depression. Commonly used screenings on the presence of apathy had low detection
rates compared to the AES and reflected both apathetic and depressive symptoms.
Psychometric evaluation of available instruments will support further research on
the clinical relevance of apathy for disease progression and treatment approaches
in PD patients.
PMID- 28418164
TI - Molecular subtyping of mammary-like adenocarcinoma of the vulva shows molecular
similarity to breast carcinomas.
AB - AIMS: Mammary-like adenocarcinoma (MLA) of the vulva is thought to be derived
from vulvar mammary-like glands. The aim of this study was to characterize a
series of MLAs by using an immunohistochemical algorithm that identifies the
major molecular subtypes of breast cancer. METHODS AND RESULTS: Seven cases of
vulval MLA were stained for oestrogen receptor (ER), progesterone receptor (PR),
human epidermal growth factor receptor 2 (HER2), Ki67, epidermal growth factor
receptor (EGFR), cytokeratin (CK) 5, nestin, and inositol polyphosphate-4
phosphatase (INPP4b). Seventeen cases of vulval extramammary Paget disease
(EMPD), seven with invasion, were studied for comparison. The median age of
patients with MLA was 72 years. All tumours except one were early-stage tumours.
On the basis of an immunohistochemical panel, three of seven tumours were
classified as luminal B, two of seven as HER2-enriched, one of seven as luminal
A, and one of seven as basal-like. ER was expressed in four of seven tumours, PR
in three of seven, HER2 in three of seven, EGFR in two of seven, and CK5 in one
of seven, and the Ki67 index was >15% in six of seven cases. Nestin and INPP4b
were, respectively, negative and positive in all cases. Of the seven cases of
invasive EMPD, two showed a luminal A profile, three a luminal B profile (two of
three with HER2 amplification), one a HER2-enriched profile, and one a basal-like
profile. Three of seven were HER2-amplified. Among the 10 cases of EMPD without
invasion, seven showed a luminal A profile and three showed a luminal B profile
(all HER2-amplified); no HER2-enriched or basal-like subtypes were identified.
CONCLUSIONS: Breast cancer subtyping can be applied to vulvar MLAs. All four
intrinsic molecular subtypes are seen, with frequencies similar to those in
breast carcinoma. Our results support the potential use of breast cancer
molecular profiling algorithms to guide treatment for these cancers.
PMID- 28418165
TI - Physical activities impact sense of coherence among community-dwelling older
adults.
AB - AIM: The objective of the present study was to investigate bidirectional
longitudinal relationships between sense of coherence (SOC) and physical
activities (PA) among community-dwelling older adults. METHODS: Self-administered
questionnaires were sent to 508 community-dwelling adults aged 65-85 years who
expressed their intention to participate in our surveys including cognitive
function tests and physical performance tests. Of these, 427 people responded to
the baseline survey, and 223 of them participated in the follow-up survey 1 year
later. Finally, the number of eligible respondents who had no missing values in
all data was 179 (valid response rate: 35.2%). We used the 13-item five-point
version of the Sense of Coherence Scale to assess SOC variables, and the Physical
Activity Scale for the Elderly to assess PA variables. A structural equation
modeling method was used to analyze bidirectional longitudinal relationships
between SOC and PA. Cross-lagged effects and synchronous effects models were
applied to analyze these relationships. Demographic variables (age, sex,
education, living arrangements, medical histories, employment status), cognitive
function and physical performance were used as control variables. RESULTS:
Leisure-time PA had a cross-lagged effect (beta = 0.117, P < 0.05) and a
synchronous effect (beta = 0.217, P < 0.001) on SOC. In contrast, no significant
effect of SOC on any type of PA was observed in either the cross-lagged effects
model or the synchronous effects model. CONCLUSIONS: Leisure-time PA might
contribute to enhancing SOC in community-dwelling older adults. Geriatr Gerontol
Int 2017; 17: 2208-2215.
PMID- 28418166
TI - Cancer Therapy: Shooting for the Moon.
PMID- 28418170
TI - Possible role of aqueous humour dynamics in Descemet's membrane detachment
resolution.
PMID- 28418171
TI - Formation of oxysterols during thermal processing and frozen storage of cooked
minced meat.
AB - BACKGROUND: Cholesterol is susceptible to oxidation and the formation of
oxysterols, which could have a negative health effect. The formation and
distribution of oxysterols was investigated in meatloaves prepared under
different baking regimes with an increased temperature or prolonged time. The
effect of frozen storage and marjoram addition on the level of oxysterols was
also investigated. RESULTS: The effect of baking regime on the content and
distribution of oxysterols was determined. Temperature was the most important
factor affecting 7-ketocholesterol formation in baked meatloaf. Its content was
significantly higher after baking at 250 degrees C compared to at 180 degrees
C. The content of 7-ketocholesterol increased from the centre (87 ug kg-1 ) to
the surface (122 ug kg-1 ) of baked meatloaves prepared under standard
conditions. The level of alpha-tocopherol and its distribution was also affected
by the baking regime. A higher level of 7-ketocholesterol was found in baked
meatloaves after their frozen storage. The addition of marjoram did not change
this level. CONCLUSION: Inadequate culinary conditions used for preparation of
baked meat can contribute to an increased oxysterol intake in the diet. Frozen
storage did not stop oxysterol formation. The inhibition effect of marjoram on
sterols oxidation was not confirmed. (c) 2017 Society of Chemical Industry.
PMID- 28418172
TI - Analgesic effect of clobazam in chronic low-back pain but not in experimentally
induced pain.
AB - BACKGROUND: Chronic pain is frequently associated with hypersensitivity of the
nervous system, and drugs that increase central inhibition are therefore a
potentially effective treatment. Benzodiazepines are potent modulators of
GABAergic neurotransmission and are known to exert antihyperalgesic effects in
rodents, but translation into patients are lacking. This study investigates the
effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim
of this study is to explore the effect of GABA modulation on chronic low-back
pain and on quantitative sensory tests. METHODS: In this double-blind cross-over
study, 49 patients with chronic low-back pain received a single oral dose of
clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10
numeric rating scale and quantitative sensory tests were assessed during 2 h
after drug intake. RESULTS: Pain intensity in the supine position was
significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs.
3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005).
Pain intensity in the sitting position was not significantly different between
groups. No effects on quantitative sensory tests were observed. CONCLUSIONS: This
study suggests that clobazam has an analgesic effect in patients with chronic low
back pain. Muscle relaxation or sedation may have contributed to the effect.
Development of substances devoid of these side effects would offer the potential
to further investigate the antihyperalgesic action of GABAergic compounds.
SIGNIFICANCE: Modulation of GABAergic pain-inhibitory pathways may be a potential
future therapeutic target.
PMID- 28418173
TI - Rebutting the inclined analyses on the cost-effectiveness and feasibility of
coral reef restoration.
PMID- 28418174
TI - Hypoxia upregulates integrin gene expression in microvascular endothelial cells
and promotes their migration and capillary-like tube formation.
AB - Tissue hypoxia affects gene expression through the hypoxia-inducible
transcription factors, HIF-1 and HIF-2, in both physiological and pathological
angiogenesis. Angiogenesis is a complex response of endothelial cells integrating
cell proliferation, migration, tube formation, and their interaction with the
extracellular matrix through integrin receptors. In this report, we studied the
effect of hypoxia on the angiogenic functions of human microvascular endothelial
cells (HMEC-1) as well as on expression of the angiogenic integrins alphanu beta3
, alphanu beta5 , and alpha5 beta1 . Exposure of HMEC-1 to hypoxia (1% O2 ) or to
DMOG, a prolyl-4-hydroxylase inhibitor, caused significant reduction to their
proliferation rate, whereas their migration ability toward laminin-1 or collagen
IV and capillary-like tube formation were significantly enhanced. In addition,
alphav , beta1 , beta3 , and beta5 integrins expression was increased under
hypoxia in HMEC-1, while alpha5 integrin was not affected. Both HIF-1 and HIF-2
protein expression and transcriptional activity were induced under hypoxia in
HMEC-1. The knockdown of either HIF-1alpha or HIF-2alpha inhibited integrin beta3
hypoxic stimulation, suggesting a HIF-dependent induction of beta3 integrin in
HMEC-1. Taken together, our results indicate that hypoxia transcriptionally up
regulates angiogenic integrins in microvascular endothelial cells along with
promoting migration and tube formation of HMEC-1.
PMID- 28418175
TI - From Bidentate Gallium Lewis Acids to Supramolecular Complexes.
AB - Bidentate gallium Lewis acids were prepared by the reaction of
diethynyldiphenylsilane with neat trimethyl- or triethylgallium.
Bis[(dimethylgallyl)ethynyl]diphenylsilane (1) and diethylgallyl derivative 2
were characterized as Et2 O or pyridine adducts by NMR spectroscopy; 2?2Py was
isolated. Lewis acids 1 and 2 form host-guest adducts with bidentate nitrogen
bases, but defined cyclic 1:1 adducts are only formed between 1 and bases with
matching N???N distances: 4,4'-dimethyl-3,3'-bipyridinylacetylene (3),
bis[(pyridin-3-yl)ethynyl]diphenylsilane (4), and bis[(2-methylpyridin-5
yl)ethynyl]diphenylsilane (5). The structures of adducts 1?3, 1?4, and 1?5 were
established by X-ray diffraction experiments. 2?2Py reacts with DABCO to afford
polymeric (DABCO-2-)n .
PMID- 28418176
TI - Panitumumab-Conjugated Pt-Drug Nanomedicine for Enhanced Efficacy of Combination
Targeted Chemotherapy against Colorectal Cancer.
AB - Targeted combination chemotherapy (TCT) has recently been used to increase the
induction of tumor cell death. In particular, the combination of Panitumumab and
the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically
effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that
overexpress epidermal growth factor receptors, and significantly greater efficacy
is observed than with either drug alone. However, low accumulation of Pt drug in
tumor sites prevents achievement of ideal efficacy. To develop an alternative
drug therapy that achieves the ideal efficacy of TCT, the novel nanomedicine
NANOPt-Pan using self-assembled dichloro(1,2-diaminocyclohexane)Pt(II)-modified
Panitumumab is generated. Treatments with NANOPt-Pan lead to significant
accumulation of Pt drug and Panitumumab in tumors, reflecting enhanced
permeability and retention effect, active targeting, and sustained circulation of
the Pt drug in the blood. In addition, NANOPt-Pan has excellent in vivo anti-CRC
efficacy. These data indicate that NANOPt-Pan has high potential as a candidate
nanomedicine for CRC.
PMID- 28418177
TI - Erdheim-Chester disease with unusual clinicopathological features complicated by
DRESS syndrome, disseminated Cytomegalovirus infection and hemophagocytic
lymphohistiocytosis.
PMID- 28418178
TI - Unfolded protein response activation compensates endoplasmic reticulum-associated
degradation deficiency in Arabidopsis.
AB - Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum
(ER) stress. There is a sophisticated ER quality control (ERQC) system to
mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The
accumulation of misfolded proteins in the ER activates the unfolded protein
response (UPR) to enhance ER protein folding and the degradation of misfolded
proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic
stress damage has been well studied in mammals and yeast. However, in plants,
both ERAD and UPR have been studied separately and found to be critical for plant
abiotic stress tolerance. In this study, we discovered that UPR-associated
transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin
(TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana
abiotic stress tolerance. They regulated the expression level of ER chaperones
and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28
and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant
hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in
Arabidopsis.
PMID- 28418179
TI - Copy number variation, increased gene expression, and molecular mechanisms of
neurofascin in lung cancer.
AB - Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin
(NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and,
while studies on NFASC are inadequate, other members have been indicated pivotal
roles in cancer progression and metastasis. This study aimed at increasing the
knowledge on the involvement of adhesion molecules in lung cancer progression by
studying the regulation and role of NFASC in non-small cell lung cancer (NSCLC).
Here, copy number variations in the NFASC gene were analyzed in tumor and non
tumorous lung tissues of 204 NSCLC patients. Frequent gene amplifications (OR =
4.50, 95%CI: 2.27-8.92, P <= 0.001) and increased expression of NFASC (P = 0.034)
were identified in tumors of NSCLC patients. Furthermore, molecular mechanisms of
NFASC in lung cancer progression were evaluated by investigating the effects of
NFASC silencing on cell proliferation, viability, migration, and invasion using
siRNA technology in four NSCLC cell lines. Silencing of NFASC did not affect cell
proliferation or viability but rather decreased NSCLC cell migration (P <= 0.001)
and led to morphological changes, rearrangements in the actin cytoskeleton and
changes in F-actin networks in migrating NSCLC cell lines. This study is the
first to report frequent copy number gain and increased expression of NFASC in
NSCLC. Moreover, these data suggest that NFASC is a novel regulator of NSCLC cell
motility and support a role of NFASC in the regulation of NSCLC progression.
PMID- 28418181
TI - Alibis: Generation, Consistency, Corroboration, Believability, and Detection -
Introduction to this Special Issue.
AB - This special issue highlights recent developments in the field of alibi research.
These include a shift from self-report studies to behavioral paradigms; a
broadening in the literature to study not only suspects, investigators, and legal
decision makers, but also alibi corroborators; and an expansion of the research
to include alibi-related memory issues rather than a sole focus on social impact
factors. Additionally, this special issue addresses the many misconceptions that
exist when it comes to the appraisal of consistency in the context of alibi
accuracy and truthfulness. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418180
TI - "Little things matter!" Exploring the perspectives of patients with dementia
about the hospital environment.
AB - BACKGROUND: Recognising demographic changes and importance of the environment in
influencing the care experience of patients with dementia, there is a need for
developing the knowledge base to improve hospital environments. Involving
patients in the development of the hospital environment can be a way to create
more responsive services. To date, few studies have involved the direct voice of
patients with dementia about their experiences of the hospital environment.
DESIGN AND METHOD: Using an action research approach, we worked with patients
with dementia and a team of interdisciplinary staff on a medical unit to improve
dementia care. The insights provided by patients with dementia in the early phase
shaped actions undertaken at the later stage to develop person-centred care
within a medical ward. We used methods including go-along interviews, video
recording and participant observation to enable rich data generation. AIM: This
study explores the perspectives of patients with dementia about the hospital
environment. RESULTS: The participants indicated that a supportive hospital
environment would need to be a place of enabling independence, a place of safety,
a place of supporting social interactions and a place of respect. CONCLUSIONS:
Patient participants persuasively articulated the supportive and unsupportive
elements in the environment that affected their well-being and care experiences.
They provided useful insights and pointed out practical solutions for
improvement. Action research offers patients not only opportunities to voice
their opinion, but also possibilities to contribute to hospital service
development. IMPLICATIONS FOR PRACTICE: This is the first study that demonstrates
the possibility of using go-along interviews and videoing with patients with
dementia staying in a hospital for environmental redesign. Researchers, hospital
leaders and designers should further explore strategies to best support the
involvement of patients with dementia in design and redesign of hospital
environments.
PMID- 28418182
TI - Cyclometalated Iridium(III) Bipyridine-Phenylboronic Acid Complexes as Bioimaging
Reagents and Luminescent Probes for Sialic Acids.
AB - Sialic acids play important roles in mammalian development, cell-cell attachment,
and signaling. As cancer cells utilize their overexpressed sialylated antigens to
propagate metastases, the development of probes for sialic acids is of high
importance. Herein, we report three luminescent cyclometalated iridium(III)
bipyridine complexes bearing a phenylboronic acid (PBA) moiety.
Spectrophotometric titrations revealed that the PBA complexes displayed higher
binding affinity for the most common sialic acid N-acetylneuraminic acid (Neu5Ac)
compared with simple sugars that are commonly found on glycoproteins. Notably,
cellular imaging and uptake experiments showed that the PBA complexes were able
to recognize cellular sialic acid residues, resulting in more efficient uptake
than the boronic acid-free analogs. Additionally, one of the PBA complexes was
shown to discriminate between cancerous and noncancerous cells.
PMID- 28418184
TI - B(C6 F5 )3 -Catalyzed Cascade Reduction of Pyridines.
AB - B(C6 F5 )3 has been found to be an effective catalyst for reduction of pyridines
and other electron-deficient N-heteroarenes with hydrosilanes (or hydroboranes)
and amines as the reducing reagents. The success of this development hinges upon
the realization of a cascade process of dearomative hydrosilylation (or
hydroboration) and transfer hydrogenation. The broad functional-group tolerance
(e.g. ketone, ester, unactivated olefins, nitro, nitrile, heterocycles, etc.)
implies high practical utility.
PMID- 28418183
TI - Evaluation of gender-based disparities in time from initial haematuria
presentation to upper tract urothelial carcinoma diagnosis: analysis of a
nationwide insurance claims database.
AB - OBJECTIVE: To investigate the length of time from initial haematuria presentation
to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on
this duration. PATIENTS AND METHODS: Patients with haematuria claims in the year
prior to UTUC diagnosis were identified from the MarketScan database (2010-2014).
Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC
diagnosis. Multivariable Poisson regression models were used to determine factors
associated with delayed UTUC diagnosis. RESULTS: Among 1 326 patients with UTUC,
469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median
interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In
the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence
interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary
tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95%
CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related
diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists,
UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new
(RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94,
95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men
presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR
1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI
0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR
1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis. CONCLUSION:
A UTUC diagnosis was made >90 days after haematuria presentation in approximately
one-third of patients. Men experienced a longer median interval from haematuria
to UTUC diagnosis compared with women, but male gender was not an independent
predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation
were strongly associated with delayed diagnosis, especially among patients
initially seen by non-urologists. Future interventions should focus on
development of non-invasive techniques to improve clinical risk stratification of
patients presenting with haematuria and to educate practitioners, especially non
urologists, with regard to the importance of a thoughtful haematuria evaluation
and the common mimickers of UTUC, to help reduce delays in diagnosis.
PMID- 28418185
TI - Cu/Pd Synergistic Dual Catalysis: Asymmetric alpha-Allylation of an alpha-CF3
Amide.
AB - Despite the burgeoning demand for fluorine-containing chemical entities, the
construction of CF3 -containing stereogenic centers has remained elusive. Herein,
we report the strategic merger of CuI /base-catalyzed enolization of an alpha-CF3
amide and Pd0 -catalyzed allylic alkylation in an enantioselective manner to
deliver chiral building blocks bearing a stereogenic carbon center connected to a
CF3 , an amide carbonyl, and a manipulable allylic group. The phosphine complexes
of CuI and Pd0 engage in distinct catalytic roles without ligand scrambling to
render the dual catalysis operative to achieve asymmetric alpha-allylation of the
amide. The stereoselective cyclization of the obtained alpha-CF3 -gamma,delta
unsaturated amides to give tetrahydropyran and gamma-lactone-fused cyclopropane
skeletons highlights the synthetic utility of the present catalytic method as a
new entry to non-racemic CF3 -containing compounds.
PMID- 28418186
TI - A Multifunctional Tb-MOF for Highly Discriminative Sensing of Eu3+ /Dy3+ and as a
Catalyst Support of Ag Nanoparticles.
AB - Exploring novel multifunctional rare earth materials is very important because
these materials have fundamental interests, such as new structural facts and
connecting modes, as well as potential technological applications, including
optics, magnetic properties, sorption, and catalytic behaviors. Especially,
employing these nanomaterials for sensing or catalytic reactions is still very
challenging. Herein, a new superstable, anionic terbium-metal-organic-framework,
[H2 N(CH3 )2 ][Tb(cppa)2 (H2 O)2 ], (China Three Gorges University (CTGU-1), H2
cppa = 5-(4-carboxyphenyl)picolinic acid), is successfully prepared, which can be
used as a turn-on, highly-sensitive fluorescent sensor to detect Eu3+ and Dy3+ ,
with a detection limitation of 5 * 10-8 and 1 * 10-4 m in dimethylformamide,
respectively. This result represents the first example of lanthanide-metal
organic-frameworks (Ln-MOF) that can be employed as a discriminative fluorescent
probe to recognize Eu3+ and Dy3+ . In addition, through ion exchanging at room
temperature, Ag(I) can be readily reduced in situ and embedded in the anionic
framework, which leads to the formation of nanometal-particle@Ln-MOF composite
with uniform size and distribution. The as-prepared Ag@CTGU-1 shows remarkable
catalytic performance to reduce 4-nitrophenol, with a reduction rate constant
kappa as large as 2.57 * 10-2 s-1 ; almost the highest value among all reported
noble-metal-nanoparticle@MOF composites.
PMID- 28418187
TI - Author response to "Letter to Editor by Roger Mepsted".
PMID- 28418188
TI - A Facile and Versatile Synthesis of Energetic Furazan-Functionalized 5-Nitroimino
1,2,4-Triazoles.
AB - An analogue-oriented synthetic route for the formulation of furazan
functionalized 5-nitroimino-1,2,4-triazoles has been explored. The process was
found to be straightforward, high yielding, and highly efficient, and scalable.
Nine compounds were synthesized and the physicochemical and energetic properties,
including density, thermal stability, and sensitivity, were investigated, as well
as the energetic performance (e.g., detonation velocities and detonation
pressures) as evaluated by using EXPLO5 code. Among the new materials, compounds
4-6 and 11 possess high densities, acceptable sensitivities, and good detonation
performances, and thereby demonstrate the potential applications as new secondary
explosives.
PMID- 28418189
TI - Epileptic manifestations in stroke patients treated with intravenous alteplase.
AB - BACKGROUND AND PURPOSE: Intravenous alteplase (rtPA) may be associated with
seizures and epileptic activity in the electroencephalogram (EEG). The aim of
this work was to compare the frequency of seizures and EEG abnormalities between
stroke patients treated and not treated with rtPA. METHODS: This was a
prospective study of consecutive acute anterior circulation ischaemic stroke
patients, with 1-year follow-up. Patients were previously independent, had an
admission National Institute of Health Stroke Scale score >=4, an acute ischaemic
lesion and no previous seizures. They received standardized diagnostic and
medical care. A video-EEG was performed in 72 h (first EEG); during admission
(daily until day 7 and after that if neurological worsening); at discharge and 1
year after stroke. RESULTS: In all, 151 patients (101 treated with rtPA) were
included. The frequency of acute and remote symptomatic seizures was not
significantly different between rtPA treated and non-treated patients (P = 0.726
and P = 0.748, respectively). Clinical paroxysmal phenomena during rtPA perfusion
were observed in five (5%) patients. In the first EEG, rtPA treated patients more
often had background diffuse slowing (43.6% vs. 26.0%, P = 0.036). This
difference was no longer observed at discharge (24.0% vs. 19.1%, P = 0.517) nor 1
year after (11.8% vs. 10.0%, P = 0.765). No differences were found in the
frequency of epileptiform (P = 0.867) or periodic discharges (P = 0.381).
CONCLUSIONS: Intravenous alteplase is not associated with an increased risk of
clinical or electroencephalographic epileptic phenomena.
PMID- 28418190
TI - Strategic Shuffling of Clay Layers to Imbue Them with Responsiveness.
AB - Layers of naturally occurring clay minerals are rearranged to prepare highly
sensitive multiresponsive clay-clay bilayer membrane (CCBM). The CCBM introduced
here responds to the minuscule changes in the surrounding environments including
temperature, humidity, and presence of solvent vapors by morphing in specific
manners. Strips cut from CCBM exhibit up to 588 N kg-1 force output when exposed
to temperature fluctuations. Inheriting the natural stability of clay minerals,
CCBM demonstrates extreme robustness, heating up to 500 degrees C, cooling with
liquid N2 and exposure to corrosive chemical vapors did not deteriorate its
bending performance. Mechanistic studies suggest that shape transformations of
CCBM are driven by the unequal response of its components to external stimuli.
PMID- 28418191
TI - Evaluation of the Chinese herbal medicine Jinlida in type 2 diabetes patients
based on stratification: Results of subgroup analysis from a 12-week trial.
AB - BACKGROUND: The Chinese herbal medicine Jinlida can significantly enhance the
hypoglycemic action of metformin. However, the population showing the best
responses to Jinlida has not been clarified. The aim of the present study was to
compare the efficacy of Jinlida in type 2 diabetes mellitus (T2DM) after
stratification. METHODS: Data were analyzed from a 12-week randomized placebo
controlled double-blind multicenter study with 192 T2DM patients (186 completed
the study). The efficacy evaluation included HbA1c, fasting plasma glucose (FPG),
and 2-h postprandial glucose (2hPG) levels stratified by baseline HbA1c, sex,
age, body mass index (BMI), and duration of T2DM diagnosis. Homeostasis model
assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of
beta-cell function (HOMA-beta) were also evaluated stratified by baseline insulin
levels. RESULTS: In the Jinlida group, HbA1c was significantly reduced (P <
0.05). Greater reductions were observed in patients with baseline HbA1c >8.5%, in
males and in those aged >60 years, with a BMI <=24 kg/m2 , or with a duration of
T2DM diagnosis >5 years (P < 0.05). Compared with baseline, Jinlida significantly
alleviated insulin resistance (P < 0.05) in patients with baseline insulin levels
>20 mU/L. Jinlida also significantly improved beta-cell function in patients with
baseline insulin levels <=20 mU/L (P < 0.05). CONCLUSIONS: Jinlida significantly
improved glycemic control, with greater improvements in patients with poor
glycemic control and male, elderly, of normal weight, or with a long disease
course. Furthermore, Jinlida alleviated insulin resistance with hyperinsulinemia
and promoted insulin secretion with hypoinsulinemia. These results need to be
further confirmed in clinical trials.
PMID- 28418193
TI - Highly Efficient Carbon Dioxide Hydrogenation to Methanol Catalyzed by Zigzag
Platinum-Cobalt Nanowires.
AB - Carbon dioxide (CO2 ) hydrogenation is an effective strategy for CO2 utilization,
while unsatisfied conversion efficiencies remain great challenges. It is reported
herein that zigzag Pt-Co nanowires (NWs) with Pt-rich surfaces and abundant
steps/edges can perform as highly active and stable CO2 hydrogenation catalysts.
It is found that tuning the Pt/Co ratio of the Pt-Co NWs, solvents, and catalyst
supports could well optimize the CO2 hydrogenation to methanol (CH3 OH) with the
Pt4 Co NWs/C exhibiting the best performance, outperforming all the previous
catalysts. They are also very durable with limited activity decays after six
catalytic cycles. The diffuse reflectance infrared Fourier transform spectroscopy
result of CO2 adsorption shows that the Pt4 Co NWs/C undergoes the
adsorption/activation of CO2 by forming appropriate carboxylate intermediates,
and thus enhancing the CH3 OH production.
PMID- 28418194
TI - Accelerated tumour metastasis due to interferon-gamma receptor-mediated
dissociation of perivascular cells from blood vessels.
AB - Angiostasis mediated by interferon (IFN)-gamma is a key mechanism of anti-tumour
immunity; however, the effect of IFN-gamma on host vascular endothelial growth
factor A (VEGFA)-expressing cells during tumour progression is still elusive.
Here, we developed transgenic mice with IFN-gamma receptor (IFNgammaR) expression
under control of the Vegfa promoter (V-gammaR). In these mice, the IFN-gamma
responsiveness of VEGFA-expressing cells led to dramatic growth suppression of
transplanted lung carcinoma cells. Surprisingly, increased mortality and tumour
metastasis were observed in the tumour-bearing V-gammaR mice, in comparison with
the control wild-type and IFNgammaR-deficient mice. Further study showed that
perivascular cells were VEGFA-expressing cells and potential IFN-gamma targets.
In vivo, tumour vascular perfusion and pericyte association with blood vessels
were massively disrupted in V-gammaR mice. In vitro, IFN-gamma inhibited
transforming growth factor-beta signalling by upregulating SMAD7, and therefore
downregulated N-cadherin expression in pericytes. Importantly, IFN-gamma
neutralization in vivo with a monoclonal antibody reduced tumour metastasis.
Together, the results suggest that IFNgammaR-mediated dissociation of
perivascular cells from blood vessels contributes to the acceleration of tumour
metastasis. Thus, the inhibition of tumour growth via IFN-gamma-induced
angiostasis might also accelerate tumour metastasis. Copyright (c) 2017
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 28418192
TI - Detection of potentially novel paramyxovirus and coronavirus viral RNA in bats
and rats in the Mekong Delta region of southern Viet Nam.
AB - Bats and rodents are being increasingly recognized as reservoirs of emerging
zoonotic viruses. Various studies have investigated bat viruses in tropical
regions, but to date there are no data regarding viruses with zoonotic potential
that circulate in bat and rat populations in Viet Nam. To address this paucity of
data, we sampled three bat farms and three wet markets trading in rat meat in the
Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened
for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses.
Paramyxovirus RNA was detected in 4 of 248 (1%) and 11 of 222 (4.9%) bat faecal
and urine samples, respectively. Coronavirus RNA was detected in 55 of 248 (22%)
of bat faecal samples; filovirus RNA was not detected in any of the bat samples.
Further, coronavirus RNA was detected in 12 of 270 (4.4%) of rat faecal samples;
all samples tested negative for paramyxovirus. Phylogenetic analysis revealed
that the bat paramyxoviruses and bat and rat coronaviruses were related to
viruses circulating in bat and rodent populations globally, but showed no cross
species mixing of viruses between bat and rat populations within Viet Nam. Our
study shows that potentially novel variants of paramyxoviruses and coronaviruses
commonly circulate in bat and rat populations in Viet Nam. Further
characterization of the viruses and additional human and animal surveillance is
required to evaluate the likelihood of viral spillover and to assess whether
these viruses pose a risk to human health.
PMID- 28418195
TI - Association between type 2 diabetes, curative treatment and survival in men with
intermediate- and high-risk localized prostate cancer.
AB - OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was
received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as
little is known about the influence of T2DM diagnosis on the receipt of such
treatment in men with localized PCa. SUBJECTS AND METHODS: The Prostate Cancer
database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n =
2210) for comparison with data on men with PCa only (n = 23 071). All men had
intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20
ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL)
localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate
logistic regression was used to calculate the odds ratios (ORs) for receipt of
curative treatment in men with and without T2DM. Overall survival, for up to 8
years of follow-up, was calculated both for men with T2DM only and for men with
T2DM and PCa. RESULTS: Men with T2DM were less likely to receive curative
treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69
0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and
high-risk PCa who did and did not receive curative treatment, respectively.
CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for
localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who
received curative treatment had substantially higher survival times than those
who did not. Some of the survival differences represent a selection bias, whereby
the healthiest patients received curative treatment. Clinicians should interpret
this data carefully and ensure that individual patients with T2DM and PCa are not
under- nor overtreated.
PMID- 28418196
TI - Clinical frailty is independently associated with non-prescription of
anticoagulants in older patients with atrial fibrillation.
AB - AIM: Anticoagulants are underused in older patients with atrial fibrillation
(AF). Scoring systems, such as CHA2 DS2 -VASc and HAS-BLED, are recommended to
guide clinicians in anticoagulation decisions, but patients' frailty might be an
underrecognized factor. We investigated the association between the Clinical
Frailty Scale (CFS) and community anticoagulant prescribing habits in patients
aged >=75 years with AF admitted acutely to hospital. METHODS: Data were gathered
retrospectively over 3 months on individuals admitted under a medical team to a
tertiary teaching hospital in the UK. Demographics, AF history, CHA2 DS2- VASc,
HAS-BLED and CFS were collected. Bivariable analysis compared anticoagulated and
non-anticoagulated groups. Each component of the CHA2 DS2 -VASc and HAS-BLED
scores, as well as frailty, age and sex, were entered in a multivariable
analysis. RESULTS: A total of 419 patients with known AF were included. Of these,
215 were not anticoagulated (51.3%) on admission. Non-anticoagulated individuals
were older (median age 87 years, [interquartile range (IQR) 7] vs 83 years [IQR
6], P < 0.001), more likely to be frail (81.4% vs 52.5%, P < 0.001) and had lower
CHA2 DS2 -VASc scores (median 4, [IQR 2] vs 5 [IQR 2], P = 0.01). In the
multivariable analysis, frailty had the strongest effect against anticoagulant
prescription (OR 0.77, 95% CI 0.70-0.85, P < 0.001) compared with other
significant risk factors, such as age (OR 0.98, 95% CI 0.97-0.98, P < 0.001) and
bleeding risk (OR 0.85, 95% CI 0.74-0.97, P = 0.02). CONCLUSIONS: Frailty is
associated with non-prescription of anticoagulants, independently of CHA2 DS2
VASc and HAS-BLED. It could be an important unmeasured factor in anticoagulation
decisions. The utility of explicit frailty measurements in anticoagulation
decisions and patient outcomes requires further research. Geriatr Gerontol Int
2017; 17: 2178-2183.
PMID- 28418197
TI - Body mass index associates with white matter microstructure in bipolar
depression.
AB - OBJECTIVES: Obesity has been reported in over 60% of bipolar disorder (BD)
patients. It worsens the severity of illness, and influences cognition and
functional outcomes. White matter (WM) abnormalities are one of the most
consistently reported findings in neuroimaging studies of BD. We hypothesized
that body mass index (BMI) could correlate with WM integrity in bipolar patients.
METHODS: We evaluated BMI in a sample of 164 depressed patients affected by BD.
We performed whole-brain tract-based spatial statistics with threshold-free
cluster enhancement for the diffusion tensor imaging (DTI) measures of WM
integrity: fractional anisotropy; axial, radial, and mean diffusivity. RESULTS:
We observed that BMI was associated with DTI measures of WM integrity in several
fiber tracts: anterior corona radiata, anterior thalamic radiation, inferior
fronto-occipital fasciculus and corpus callosum. CONCLUSIONS: The association of
BMI in key WM tracts that are crucial to mood regulation and neurocognitive
functioning suggests that BMI might contribute to the pathophysiology of BD
through a detrimental action on structural connectivity in critical cortico
limbic networks.
PMID- 28418198
TI - Stress is associated with an increased risk of recurrent seizures in adults.
AB - OBJECTIVE: The literature is sparse on the complex interrelationships between
stressors, depression, anxiety disorders, and epilepsy. We hypothesized that a
relationship exists between stress and epilepsy. We evaluated whether markers of
stress are associated with seizure recurrence in a low income community-based
cohort of adults with single unprovoked seizure or newly diagnosed epilepsy.
METHODS: We ascertained adult residents of Northern Manhattan and Harlem, New
York City, with a first unprovoked seizure or newly diagnosed epilepsy, between
December 2010 and January 2013. At enrollment, we collected information about
seizure phenomenology, demographics, clinical information, and measures of stress
(environmental stress, stressful life events, facets of allostatic load-i.e., the
cumulative effect of adaptation to stress, psychiatric disorders, and low
collective efficacy). Collective efficacy assesses neighborhood characteristics
and incorporates social cohesion and informal social control. All subjects were
followed for 2 years for further seizures. Cox proportional hazard regression
models were used to estimate the hazard ratios of seizure recurrence during the 2
years of follow-up. RESULTS: We identified 52 subjects (64.2%) with a single
unprovoked seizure and 29 (35.9%) with newly diagnosed epilepsy. Seizure
recurrence was recorded in 38.5% (N = 20) of subjects with a single unprovoked
seizure and in 69% of those with epilepsy (N = 20) (p = 0.01). In the overall
sample, the hazard of seizure recurrence was increased by lifetime generalized
anxiety disorder (3.0-fold) and by low collective efficacy (2.7-fold). In a
second model, the hazard was increased by lifetime mood disorder (2.1-fold) and
low collective efficacy (2.5-fold). SIGNIFICANCE: Markers of stress (i.e., low
collective efficacy, lifetime mood disorder, and lifetime generalized anxiety
disorder) were associated with an increased risk for seizure recurrence in adults
with a single unprovoked seizure or newly diagnosed epilepsy. Stress-reducing
interventions, such as mindfulness, may be a useful, safe, and inexpensive
adjunctive treatment for epilepsy.
PMID- 28418200
TI - Lewis Acid Promoted Single C-F Bond Activation of the CF3 Group: SN 1'-Type 3,3
Difluoroallylation of Arenes with 2-Trifluoromethyl-1-alkenes.
AB - Activation of the sp3 C-F bond in 2-trifluoromethyl-1-alkenes was accomplished
through treatment with a Lewis acid. In the presence of an equimolar amount of
EtAlCl2 , the (trifluoromethyl)alkenes readily underwent an SN 1'-type reaction
with arenes through a Friedel-Crafts-type mechanism via elimination of a fluoride
ion to afford 3,3-difluoroallylated arenes in good yields. This selective
activation of one C-F bond of the CF3 group provides a synthetic method for
accessing biologically and synthetically important 1,1-difluoro-1-alkenes.
PMID- 28418199
TI - Evaluation of Biological Activity and Computer-Aided Design of New Soft
Glucocorticoids.
AB - Soft glucocorticoids are compounds that are biotransformed to inactive and non
toxic metabolites and have fewer side effects than traditional glucocorticoids. A
new class of 17beta-carboxamide steroids has been recently introduced by our
group. In this study, local anti-inflammatory activity of these derivatives was
evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with
the highest maximal edema inhibition (MEI) were pointed out, and the systemic
side effects of those with the lowest EC50 values were significantly lower in
comparison to dexamethasone. A 3D-QSAR model was created and employed for the
design of 27 compounds. By use of the sequential combination of ligand-based and
structure-based virtual screening, three compounds were selected from the ChEMBL
library and used as a starting point for the design of 15 derivatives. Molecular
docking analysis of the designed derivatives with the highest predicted MEI and
relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7,
VS13, and VS14) confirmed the presence of interactions with the glucocorticoid
receptor that are important for the activity.
PMID- 28418201
TI - Chemoinformatics at IFP Energies Nouvelles: Applications in the Fields of Energy,
Transport, and Environment.
AB - The objective of the present paper is to summarize chemoinformatics based
research, and more precisely, the development of quantitative structure property
relationships performed at IFP Energies nouvelles (IFPEN) during the last decade.
A special focus is proposed on research activities performed in the
"Thermodynamics and Molecular Simulation" department, i. e. the use of multiscale
molecular simulation methods in responses to projects. Molecular simulation
techniques can be envisaged to supplement dataset when experimental information
lacks, thus the review includes a section dedicated to molecular simulation
codes, development of intermolecular potentials, and some of their possible
applications. Know-how and feedback from our experiences in terms of machine
learning application for thermophysical property predictions are included in a
section dealing with methodological aspects. The generic character of
chemoinformatics is emphasized through applications in the fields of energy,
transport, and environment, with illustrations for three IFPEN business units:
"Transports", "Energy Resources", and "Processes". More precisely, the review
focus on different challenges such as the prediction of properties for
alternative fuels, the prediction of fuel compatibility with polymeric materials,
the prediction of properties for surfactants usable in chemical enhanced oil
recovery, and the prediction of guest-host interactions between gases and
nanoporous materials in the frame of carbon dioxide capture or gas separation
activities.
PMID- 28418202
TI - Benzodioxole-Pyrazole Hybrids as Anti-Inflammatory and Analgesic Agents with COX
1,2/5-LOX Inhibition and Antioxidant Potential.
AB - Two series of benzodioxole-pyrazole hybrids were synthesized and the IC50 values
for in vitro inhibition of the enzymes cyclooxygenase 1/2 (COX-1, COX-2) and 5
lipoxygenase (5-LOX) were investigated. All compounds were tested for their in
vivo anti-inflammatory and analgesic potentials using diclofenac sodium as a
reference standard. Compounds 4, 11, 17, 20, 21, 26, and 27, which showed good
analgesic and/or anti-inflammatory activities, were also evaluated for their
ability to inhibit tumor necrosis factor (TNF)-alpha production, myeloperoxidase
and proteinase, beside their antioxidant activity. Collectively, compounds 11,
17, and 26 displayed significant anti-inflammatory, analgesic, and antioxidant
activities, beside dual COX-2 and 5-LOX inhibition. Among these, compound 26
showed high selectivity for in vitro COX-1/COX-2 inhibition, whereas the analogs
11 and 17 noticeably ameliorated the TNF-alpha level by 85.19 and 97.71%,
respectively. A molecular docking study was performed to investigate the possible
binding mode of compounds 11, 17, and 26 with the active sites of the COX-2 and 5
LOX enzymes, where they showed nearly the same binding pattern as that of
celecoxib and meclofenamic acid, respectively.
PMID- 28418203
TI - Effectiveness of vildagliptin as add-on to metformin monotherapy among
uncontrolled type 2 diabetes mellitus patients in a real-world setting.
AB - BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a
dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the
treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with
vildagliptin and metformin has been established in randomized controlled trials,
but there is little evidence from observational studies. The aims of the present
study were to evaluate the effectiveness of vildagliptin as an add-on therapy to
metformin in reducing HbA1c and its affects on body weight and blood lipids in a
real-life setting. METHODS: Included in the present retrospective cohort were
T2DM patients (n = 345) who were uncontrolled on metformin monotherapy and
intensified treatment with vildagliptin. The efficacy of at least 90 days of dual
therapy with vildagliptin and metformin in reducing HbA1c levels, as well as
changes in blood lipids and body weight, were evaluated. RESULTS: After 180 days
(range 90-365 days) from the index date with a mean daily dose of 92 mg
vildagliptin, HbA1c was significantly (P < 0.001) reduced by an average of 0.9%
(95% confidence interval -1.0%, -0.7%). The absolute reduction in HbA1c was
positively associated with baseline HbA1c levels. In addition to HbA1c, a modest
but significant (P < 0.05) decrement was also calculated in the patients' body
weight and blood lipids. CONCLUSIONS: The present analysis of real-world data
corroborates the results of previous randomized controlled trials indicating that
add-on therapy with vildagliptin in uncontrolled patients on metformin
monotherapy is associated with a significant improvement in the control of HbA1c.
PMID- 28418204
TI - Modeling aesthetics to support an ecosystem services approach for natural
resource management decision making.
AB - This paper reviews literature on aesthetics and describes the development of
vista and landscape aesthetics models. Spatially explicit variables were chosen
to represent physical characteristics of natural landscapes that are important to
aesthetic preferences. A vista aesthetics model evaluates the aesthetics of
natural landscapes viewed from distances of more than 1000 m, and a landscape
aesthetics model evaluates the aesthetic value of wetlands and forests within
1000 m from the viewer. Each of the model variables is quantified using spatially
explicit metrics on a pixel-specific basis within EcoAIMTM, a geographic
information system (GIS)-based ecosystem services (ES) decision analysis support
tool. Pixel values are "binned" into ranked categories, and weights are assigned
to select variables to represent stakeholder preferences. The final aesthetic
score is the weighted sum of all variables and is assigned ranked values from 1
to 10. Ranked aesthetic values are displayed on maps by patch type and integrated
within EcoAIM. The response of the aesthetic scoring in the models was tested by
comparing current conditions in a discrete area of the facility with a
Development scenario in the same area. The Development scenario consisted of two
6-story buildings and a trail replacing natural areas. The results of the vista
aesthetic model indicate that the viewshed area variable had the greatest effect
on the aesthetics overall score. Results from the landscape aesthetics model
indicate a 10% increase in overall aesthetics value, attributed to the increase
in landscape diversity. The models are sensitive to the weights assigned to
certain variables by the user, and these weights should be set to reflect
regional landscape characteristics as well as stakeholder preferences. This
demonstration project shows that natural landscape aesthetics can be evaluated as
part of a nonmonetary assessment of ES, and a scenario-building exercise provides
end users with a tradeoff analysis in support of natural resource management
decisions. Integr Environ Assess Manag 2017;13:926-938. (c) 2017 SETAC.
PMID- 28418205
TI - It's not just what you know: junior trainees' approach to follow-up and
documentation.
AB - CONTEXT: In teaching hospitals, junior trainees (first-year residents and third
year medical students) are responsible for patient follow-up and documentation
under the supervision of senior team members. In order to support trainees in
their role, supervisors need to understand how trainees approach these tasks and
how they can be coached to develop best practices. OBJECTIVES: The purpose of our
study was to explore the range of practices used by junior trainees in clinical
settings. METHODS: Constructivist grounded theory was used to guide the
collection and analysis of data on follow-up and documentation during 34
observation periods with 17 junior trainees. Data sources included field notes,
field interviews and de-identified copies of patient charts. We also held two
focus groups with four attending physicians in each. RESULTS: We were able to
describe three interrelated characteristics that influenced a trainee's approach
to and ability to perform the tasks of patient follow-up and documentation: (i)
diligence; (ii) relationship to the team (dependent, independent, collaborative),
and (iii) level of performance (Data Gatherer, Sensemaker, Manager). Diligence
and relationship to the team appeared to influence the quality and focus of a
trainee's approach at all levels of performance. Level of performance was felt,
by focus group attending physicians, to reflect a developmental progression of
knowledge and skills. CONCLUSIONS: Our findings contribute to the existing
literature in three ways. Firstly, they extend our understanding of how junior
trainees approach the task of in-patient follow-up and clinical documentation and
the value of those activities. Secondly, they provide new insights to support
formative and summative assessment. Finally, they contribute to a growing body of
literature exploring the factors that impact trainees' roles and interactions
with the team. Future research should focus on validating our findings and
exploring their utility in the development of novel assessment strategies.
PMID- 28418206
TI - Anti-NMDA-receptor encephalitis during pregnancy: A case report and literature
review.
AB - Anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is an autoimmune
disorder that was first described by Dr Vitaliani in 2005. In 2007, Dalmau et al.
found anti-NMDA-R antibody expressed both in the hippocampus and prefrontal nerve
cell membrane, finally proposing the diagnosis of autoimmune anti-NMDA-R
encephalitis. Most of the patients are female (91%), with ages ranging from 4 to
76 years. The average age is 23 years, a birth peak age, although anti-NMDA-R
encephalitis is rare during pregnancy. The disorder is characterized by prominent
psychosis, dyskinesias, seizures, autonomic disturbance, and central
hypoventilation. We report a 24-year-old woman hospitalized at 28 gestational
weeks with acute-onset psychosis. Over the course of 3 weeks, her mental status
worsened until she fell into a coma. Both serum and cerebrospinal fluid anti-NMDA
R antibodies were found to be positive. At cesarean section, a healthy baby boy
was born and a wedge-shaped bilateral ovarian resection was performed. Treatment
with corticosteroids, intravenous immunoglobulin, and plasmapheresis can lead to
improved outcomes for both mother and baby.
PMID- 28418207
TI - Pyoderma gangrenosum in a pregnant patient: A case report and literature review.
AB - Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that usually starts
as a pustular lesion and rapidly progresses to a painful ulcer with undermined
violaceous borders. The occurrence of PG during pregnancy is uncommon. We
describe a case of a pregnant patient with PG who was diagnosed as having
ulcerative colitis after delivery. Obstetricians need to understand the
pathogenesis of PG and its associated conditions because it is important to make
a proper diagnosis and provide targeted therapy.
PMID- 28418208
TI - Accuracy of self-collected human papillomavirus samples from Japanese women with
abnormal cervical cytology.
AB - AIM: The aim of this study was to assess the accuracy of self-collected vaginal
samples compared with physician-collected cervical samples for high-risk human
papillomavirus (HPV) testing in Japanese women with abnormal cervical cytology.
We also assessed the acceptability of self-collected HPV (sHPV) testing using a
questionnaire. METHODS: Women aged 20-69 years (n = 136) attending Yokohama City
University Hospital because of abnormal cervical cytology between April 2014 and
January 2015 were enrolled in this study. Cervical samples for conventional
cytology and physician-collected HPV (pHPV) testing were obtained before
colposcopic examination. After this examination, patients were asked to provide a
self-sampled vaginal specimen (sHPV) at home, some time between the following day
and the next week and to complete a self-sampling acceptability questionnaire.
RESULTS: The overall positive rates of HPV detection with pHPV and sHPV testing
were 61.0% (83/136) and 40.4% (55/136), respectively (P < 0.001). sHPV testing
had a lower sensitivity compared to pHPV for detection of cervical
intraepithelial neoplasia (CIN)2 or worse (CIN2+: 59.4% vs 100%, P < 0.001; CIN3:
66.7% vs 100%, P = 0.248). There were no statistically significant differences in
the sensitivity to detect CIN3 among pHPV testing, sHPV testing, and cytology.
The self-collecting device had good acceptability. CONCLUSION: sHPV testing is a
possible technique with which to improve poor cervical cancer screening uptake
rates in Japan; however, the sensitivity to detect CIN2+ lesions must improve
before it can be a substitute for conventional cytology or pHPV testing. Further
large-scale acceptability studies involving non-responders are also needed before
practical application.
PMID- 28418210
TI - Corrigendum.
PMID- 28418209
TI - Acupressure as adjuvant treatment for the inpatient management of nausea and
vomiting in early pregnancy: A double-blind randomized controlled trial.
AB - AIM: To evaluate the efficacy of acupressure at the Neiguan point (Pericardium
[P]6) as adjuvant treatment during inpatient management of severe nausea and
vomiting in pregnancy. METHODS: Low risk, spontaneously conceived singleton
pregnancies were randomly assigned to a treatment group, who received an
acupressure band placed at the Neiguan point (P6) or a placebo group who received
an otherwise identical non-stimulating wristband. Participants wore the band for
12 h daily for the first three days of admission. The primary outcome measure was
the severity of symptoms of nausea, vomiting and retching, recorded according to
Pregnancy-Unique Quantification of Emesis and Nausea score. RESULTS: There was a
statistically significant improvement in Pregnancy-Unique Quantification of
Emesis and Nausea scores from day 1 until day 3 of admission in the treatment
group compared with the placebo. Patients who received Neiguan point acupressure
also showed a significant improvement in their ketonuria scores. The treatment
group required a shorter hospital stay compared with the placebo. The only
reported side effect of the acupressure band was redness on the wrist.
CONCLUSIONS: The use of the acupressure band at the Neiguan point (P6) for 12 h
daily for three days for inpatients with hyperemesis gravidarum significantly
reduced the symptoms of nausea, vomiting and retching and ketonuria and led to a
reduction in hospital stay. We recommend the use of the acupressure band at the
Neiguan point (P6) as an adjunct/supplementary therapy to co-exist with the
standard care of management for hyperemesis gravidarum, particularly in low-risk
pregnant women.
PMID- 28418211
TI - Cutting costs and standardizing care: Once-per-cycle complete blood count
monitoring may be safe for patients undergoing platinum-based chemotherapy.
AB - AIM: The aim of this study was to evaluate whether frequency of complete blood
count (CBC) testing during chemotherapy for gynecologic cancer impacts hospital
admissions or rates of neutropenic fever. METHODS: A retrospective cohort study
was performed at a single academic institution. Patients undergoing platinum
based chemotherapy for endometrial or ovarian cancer from January 2010 to
December 2014 were identified from a clinical database. Patients receiving dose
dense chemotherapy or on a clinical trial were excluded. Electronic chart review
collected demographic and clinical characteristics. The primary outcome was the
rate of febrile neutropenia or hospital admission. RESULTS: A total of 174
patients were identified, 63 (36%) with endometrial and 111 (64%) with ovarian
cancer. Fifty-four percent of patients received multiple CBC per cycle compared
with 46% who only had one CBC per cycle. The majority of patients were treated
with a platinum-based doublet (85%). Dose reductions, addition of granulocyte
colony stimulating factor, and rates of grade 3 or 4 anemia and neutropenia were
significantly associated with more frequent testing. There was no difference in
rates of neutropenic fever (5.3 vs 3.8%, P = 0.45) or hospital admission (22.3 vs
21.3%, P = 0.86) for multiple versus single CBC monitoring. CONCLUSION: More
frequent laboratory testing detected more cases of grade 3 or 4 hematopoietic
toxicities and was associated with more interventions. There were no differences
in number of hospitalizations or cases of neutropenic fever by frequency of
laboratory testing, suggesting that it may be appropriate to decrease routine
laboratory tests for select patients.
PMID- 28418212
TI - Role of autophagy in oocytogenesis, embryogenesis, implantation, and
pathophysiology of pre-eclampsia.
AB - Autophagy is a well-conserved mechanism in cells from yeast to mammals, and
autophagy maintains homeostasis against stress. The role of autophagy was
originally shown to be a mechanism of energy production under starvation. In
fact, multiple lines of evidence reveal that autophagy has numerous functions,
such as protection from stress, energy regulation, immune regulation,
differentiation, proliferation, and cell death. In the field of reproduction, the
role of autophagy in implantation, embryogenesis, placentation, and delivery has
become clearer. In addition, recent study has elucidated that the placenta has
the ability to protect extraplacental cells from virus infection by activating
autophagy. During resent research into autophagy, several issues have occurred in
the interpretation of the autophagy status. In this review, we discuss the
relation between autophagy and reproductive events, and show the importance of
autophagy for placentation and pre-eclampsia.
PMID- 28418213
TI - Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with
erythromelalgia, including the I848Tmutation in NaV 1.7.
AB - OBJECTIVES: Nociceptive thresholds and supra-threshold pain ratings as well as
their reduction upon local injection with lidocaine were compared between healthy
subjects and patients with erythromelalgia (EM). METHODS: Lidocaine (0.25, 0.50,
1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful
areas of the lower arm, in a randomized, double-blind manner, to test the effect
on dynamic and static mechanical sensitivity, mechanical pain sensitivity,
thermal thresholds and supra-threshold heat pain sensitivity. RESULTS: Heat pain
thresholds and pain ratings to supra-threshold heat stimulation did not differ
between EM-patients (n = 27) and controls (n = 25), neither did the dose-response
curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium
channel subunits NaV 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity
for supra-threshold heat stimuli, contrasting lower sensitivity to strong
mechanical stimuli. This pattern was particularly clear in the two patients
carrying the NaV 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on
mechanical pain sensitivity contrasted more effective heat analgesia. CONCLUSION:
Heat pain thresholds are not sensitized in EM patients, even in those with gain
of-function mutations in NaV 1.7. Differential lidocaine sensitivity was overt
only for noxious stimuli in the supra-threshold range suggesting that sensitized
supra-threshold encoding is important for the clinical pain phenotype in EM in
addition to lower activation threshold. Intracutaneous lidocaine dose-dependently
blocked nociceptive sensations, but we did not identify EM patients with
particular high lidocaine sensitivity that could have provided valuable
therapeutic guidance. SIGNIFICANCE: Acute pain thresholds and supra-threshold
heat pain in controls and patients with erythromelalgia do not differ and have
the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients
with the NaV 1.7 I848T mutation are normal and only nociceptor sensitivity to
intradermal lidocaine is changed. Only in EM patients with mutations in NaV 1.7,
1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine
sensitivity as compared to controls.
PMID- 28418214
TI - Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904
galactooligosaccharide use in humans.
AB - BACKGROUND: We have shown that a galactooligosaccharide prebiotic administration
(HOST-G904) initially increased intestinal gas production and this increase
declined back to baseline after 2 week administration. Our aim was to determine
the mechanism of microbiota adaptation; i.e., to determine whether the net
reduction is due to decreased overall production or increased gas consumption.
METHODS: In 10 healthy subjects, intestinal gas production and intraluminal
disposal was measured before, at the beginning and after 2 week of HOST-G904
prebiotic administration. Anal gas was collected for 4 hour after a probe meal.
Paired studies were performed without and with high-rate infusion of exogenous
gas (24 mL/min) into the jejunum to wash-out the endogenous gas produced by
bacterial fermentation. The exogenous gas infused was labeled (5% SF6 ) to
calculate the proportion of endogenous gas evacuated. KEY RESULTS: The volume of
intestinal gas produced i.e., endogenous gas washed-out, increased by 37% at the
beginning of HOST-G904 administration (P=.049 vs preadministration) and decreased
down to preadministration level after 2 week administration (P=.030 vs early
administration). The proportion of gas eliminated from the lumen before reaching
the anus tended to increase after 2-week administration (87+/-3% vs 78+/-5%
preadministration; P=.098). CONCLUSIONS & INFERENCES: Adaptation to regular
consumption of HOST-G904 prebiotic involves a shift in microbiota metabolism
toward low-gas producing pathways, with a non-significant increase in gas
consuming activity. Hence, regular consumption of HOST-G904 regulates intestinal
gas metabolism: less gas is produced and a somewhat larger proportion of it is
consumed.
PMID- 28418215
TI - Multichannel Porous TiO2 Hollow Nanofibers with Rich Oxygen Vacancies and High
Grain Boundary Density Enabling Superior Sodium Storage Performance.
AB - TiO2 as an anode for sodium-ion batteries (NIBs) has attracted much recent
attention, but poor cyclability and rate performance remain problematic owing to
the intrinsic electronic conductivity and the sluggish diffusivity of Na ions in
the TiO2 matrix. Herein, a simple process is demonstrated to improve the sodium
storage performance of TiO2 by fabricating a 1D, multichannel, porous binary
phase anatase-TiO2 -rutile-TiO2 composite with oxygen-deficient and high grain
boundary density (denoted as a-TiO2-x /r-TiO2-x ) via electrospinning and
subsequent vacuum treatment. The introduction of oxygen vacancies in the TiO2
matrix enables enhanced intrinsic electronic conductivity and fast sodium-ion
diffusion kinetics. The porous structure offers easy access of the liquid
electrolyte and a short transport path of Na+ through the pores toward the TiO2
nanoparticle. Furthermore, the high density of grain boundaries between the
anatase TiO2 and rutile TiO2 offer more interfaces for a novel interfacial
storage. The a-TiO2-x /r-TiO2-x shows excellent long cycling stability (134 mAh g
1 at 10 C after 4500 cycles) and superior rate performance (93 mAh g-1 after 4500
cycles at 20 C) for sodium-ion batteries. This simple and effective process could
serve as a model for the modification of other materials applied in energy
storage systems and other fields.
PMID- 28418216
TI - Adult attachment insecurity is positively associated with medically unexplained
chronic pain.
AB - BACKGROUND: Attachment insecurity (i.e. anxiety in relationships and/or
discomfort in close relationships) is associated with self-reports of physical
symptoms, medically unexplained symptoms and health conditions involving pain.
Medically unexplained chronic pain (MUCP) may represent a particularly severe
form of symptom reporting that is also characteristic of individuals with
insecure attachment. This study investigated relationships between adult
attachment style ratings and past-year MUCP in a sample of the general U.S.
population and the ability of attachment style ratings to account for variance in
past-year MUCP beyond that accounted for by potential confounders. METHOD: Data
from the National Comorbidity Survey Replication (N = 5645) were used. Attachment
was assessed with an interview-administered version of a commonly used self
report measure of secure, anxious and avoidant attachment. MUCP was assessed with
a brief interview. Depressive and anxiety disorders were included as covariates
and were assessed with a fully structured interview based on DSM-IV criteria.
RESULTS: The past-year prevalence of MUCP was 2.45% (95% CI = 2.07-2.83). The two
insecure attachment styles (i.e. anxious and avoidant) were positively associated
with MUCP. These associations remained statistically significant after adjusting
for demographic variables and depressive and anxiety disorders. When the two
insecure attachment styles were considered together, only avoidant attachment
remained significantly associated with MUCP. CONCLUSION: Attachment insecurity
ratings were positively associated with past-year MUCP and remained so after
statistically adjusting for depressive and anxiety disorders. Further research
aimed at understanding the mechanism(s) responsible for the association between
attachment insecurity and MUCP is warranted. SIGNIFICANCE: Consistent with
earlier research regarding transient physical symptoms, medically unexplained
chronic pain was associated with attachment insecurity. Understanding the
mechanisms responsible for this association could guide treatment innovations.
PMID- 28418217
TI - Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes
patients based on continuous glucose monitoring.
AB - AIMS/INTRODUCTION: High fluctuations in blood glucose are associated with various
complications. The correlation between glycated hemoglobin (HbA1c) level and
fluctuations in blood glucose level has not been studied in Japanese patients
with type 2 diabetes. In the present study, blood glucose profile stratified by
HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type
2 diabetes patients. MATERIALS AND METHODS: Our retrospective study included 294
patients with type 2 diabetes who were divided by HbA1c level into five groups
(>=6.0 to <7.0%, >=7.0 to <8.0%, >=8.0 to <9.0%, >=9.0 to <10.0% and >=10%). The
correlation between HbA1c level and CGM data was analyzed. The primary end-point
was the difference in blood glucose fluctuations among the HbA1c groups. RESULTS:
The mean blood glucose level increased significantly with increasing HbA1c
(Ptrend < 0.01). The standard deviation increased with increases in HbA1c
(Ptrend < 0.01). The mean amplitude of glycemic excursions did not vary
significantly with HbA1c. The levels of maximum blood glucose, minimum blood
glucose, each preprandial blood glucose, each postprandial maximum blood glucose,
range of increase in postprandial glucose from pre-meal to after breakfast, the
area under the blood concentration-time curve >180 mg/dL and percentage of the
area under the blood concentration-time curve >180 mg/dL were higher with higher
HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant
and independent determinants of HbA1c. CONCLUSIONS: In Japanese patients treated
for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate
with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c.
Parameters other than HbA1c are required to evaluate fluctuations in blood
glucose level in patients receiving treatment for type 2 diabetes.
PMID- 28418218
TI - Regulation of salt marsh mosquito populations by the 18.6-yr lunar-nodal cycle.
AB - The 18.6-yr lunar-nodal cycle drives changes in tidal amplitude globally,
affecting coastal habitat formation, species and communities inhabiting rocky
shores, and salt marsh vegetation. However, the cycle's influence on salt marsh
fauna lacked sufficient long-term data for testing its effect. We circumvented
this problem by using salt marsh mosquito records obtained over a period of over
four decades in two estuaries in the northeastern USA. Salt marsh mosquito
habitat is near the highest tide level where the impact of the nodal cycle on
flood frequency is greatest. Wavelet spectral and cross-correlation analyses
revealed periodicity in salt marsh mosquito abundance that was negatively
correlated with tidal amplitude. Tidal amplitude was a significant predictor of
salt marsh mosquito abundance with the cycle maxima coinciding with lower
mosquito populations, possibly due to access by predatory fish. However, these
effects were detected only at the location with extensive salt marsh habitat and
astronomical tides and were weakened or lacked significance at the location with
small microtidal salt marshes and wind-driven tides. Mosquitoes can serve as
proxy indicators for numerous invertebrate species on the salt marsh. These
predictable cycles and their effects need to be taken into consideration when
investigating, restoring, or managing intertidal communities that are also facing
sea-level rise.
PMID- 28418219
TI - Alpha-2 macroglobulin as a region-specific secretory protein in male reproductive
tract, and its dynamics during sperm transit toward the female spermatheca in the
blue crab.
AB - A 250-kDa protein was isolated from fluid in the middle spermatic duct (MSD) of
the blue crab (Portunus pelagicus). N-terminal and partial amino acid sequences
revealed that this MSD-specific protein is highly similar to the plasma-enriched
protein Alpha-2 macroglobulin (alpha2M). The P. pelagicus ortholog (Ppalpha2M) is
a large glycoprotein possessing mannose and N-acetylglucosamine residues. Ppa2m
mRNA was detected in the spermatic duct, androgenic gland, and hematopoietic
tissue, whereas the protein was primarily observed in the apical cytoplasm of MSD
epithelium and in the matrix of the acrosome of MSD sperm; distally within
spermatic duct, Ppalpha2M was lost from the sperm membrane but remained in the
sperm acrosome. These results suggest that Ppalpha2M is expressed and
glycosylated in the epithelium of spermatic ducts, secreted into MSD fluid, taken
up by sperm in the MSD, and removed from the surface of sperm during its transit
towards the female spermatheca. Given that Ppalpha2M also exhibits protease
inhibitor activity, we hypothesize that acrosome localized Ppalpha2M may suppress
premature acrosome reaction during post-testicular sperm maturation in this crab.
PMID- 28418220
TI - Diabetes technology.
PMID- 28418222
TI - Modified loop myopexy technique for severe high myopic strabismus fixus.
AB - IMPORTANCE: This study introduces a modified loop myopexy technique for severe
high myopic strabismus fixus. BACKGROUND: This study aims to evaluate the
surgical results of loop myopexy with or without medial rectus recession for the
treatment of patients with myopic strabismus fixus. DESIGN: This is a
retrospective study in a Chinese teaching hospital. PARTICIPANTS: Data was
collected from 25 myopic strabismus fixus patients (33 eyes) with restriction in
both abduction and sursumduction. METHODS: First, the loop myopexy technique was
performed. Following the loop myopexy technique, a medial rectus recession was
performed if esotropia remained. If esotropia and/or hypotropia still persisted,
second-stage surgery of the contralateral eye was performed. MAIN OUTCOME
MEASURES: The main outcome measures were ocular deviations, eye movements and the
angles of dislocation of the globe. RESULTS: At the last follow-up, mean
deviation of esotropia was significantly improved (10 vs. 92 PD; p = 0.000),
while mean deviation of hypotropia was improved (6 vs. 32 PD; p = 0.008). Mean
abduction limitation was improved (-2.7 vs. -5.0; p = 0.000); mean elevation
limitation improved (-3.2 vs. -5.0; p = 0.000). The angle of dislocation of the
globe was significantly decreased (103.0 vs. 235.3 D; p = 0.002). CONCLUSIONS AND
RELEVANCE: Modified Yokoyama's surgery effectively corrected the restrictive
esotropia and hypotropia, restored the dislocated globe back into the muscle cone
and improved the eye movement in severe myopic strabismus fixus.
PMID- 28418223
TI - Hydronium Ion Batteries: A Sustainable Energy Storage Solution.
AB - Hydronium ions have been reversibly stored for the first time in an electrode of
crystalline 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA). A highly
reversible discharge-charge behavior of PTCDA was observed in an aqueous acidic
electrolyte of 1 m H2 SO4 . The capacity and the operation potentials are
comparable to that of Na-ion storage in the same electrode.
PMID- 28418224
TI - A new drug nomenclature for psychiatry - prospects and hazards.
PMID- 28418225
TI - An Iterative Module in the Azalomycin F Polyketide Synthase Contains a Switchable
Enoylreductase Domain.
AB - Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the
biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp.
211726 has shown that only nineteen extension modules are required to accomplish
twenty cycles of polyketide chain elongation. Analysis of the products of a PKS
mutant specifically inactivated in the dehydratase domain of extension-module 1
showed that this module catalyzes two successive elongations with different
outcomes. Strikingly, the enoylreductase domain of this module can apparently be
"toggled" off and on : it functions in only the second of these two cycles. This
novel mechanism expands our understanding of PKS assembly-line catalysis and may
explain examples of apparent non-colinearity in other modular PKS systems.
PMID- 28418227
TI - Barriers and facilitators to implementing family support and education in Early
Psychosis Intervention programmes: A systematic review.
AB - Family support is a core component of the Early Psychosis Intervention (EPI)
model, yet it continues to have relatively low rates of implementation in
practice. This paper reports results of a literature review on facilitators and
barriers to delivering family interventions in EPI programmes. A search was
conducted of 4 electronic databases, Medline, EMBASE, PsycINFO and Joanna Briggs,
from 2000 to 2015 using terms related to early onset psychosis, family work and
implementation. Four thousand four hundred and two unique studies were
identified, 7 of which met inclusion criteria. Barriers and facilitators were
coded and aggregated to higher-level themes using a consensus approach. Five of 7
studies examined structured multifamily psychoeducation. Uptake by families was
affected by: family/client interest and readiness to participate; ability to
access supports; and support needs/preferences. Implementation by programmes was
affected by staff access to training and resources to provide family support. A
key finding across the identified studies was that families have different needs
and preferences regarding the timing, length, intensity and content of the
intervention. One size does not fit all and many families do not require the
intensive psychoeducational programmes typically provided. The reviewed
literature suggests that flexible, tiered approaches to care may better meet
family needs and increase rates of uptake of family support. However, more
research is needed on the effectiveness of different models of family support in
early psychosis and how they can be successfully implemented.
PMID- 28418226
TI - Serum monomeric laminin-gamma2 as a novel biomarker for hepatocellular carcinoma.
AB - The diagnosis of hepatocellular carcinoma (HCC) in the early stages is important
for successful clinical management. Laminin (Ln)-gamma2 expression has been
reported in various types of malignant carcinomas. We recently developed a highly
sensitive method to measure serum monomeric Ln-gamma2 levels using a fully
automated chemiluminescent immunoassay (CLIA). Using our CLIA, we evaluated its
diagnostic value in sera from patients with chronic liver disease (CLD) and
patients with hepatocellular carcinoma (HCC). Serum alpha-fetoprotein (AFP) and
des-gamma-carboxy prothrombin (DCP) were also examined in these subjects. Median
levels of Ln-gamma2 were significantly higher in patients with HCC (173.2 pg/mL;
range: 39.5-986 pg/mL) compared with patients with CLD (76.7 pg/mL; range: 38.7
215.9 pg/mL) and with healthy volunteers (41.1 pg/mL; range: 10.9-79.0 pg/mL).
The optimal cutoff value for Ln-gamma2 that allowed us to distinguish between HCC
and nonmalignant CLD was 116.6 pg/mL. Elevated Ln-gamma2 levels were observed in
0% of healthy volunteers, 17% of patients with CLD, and 63% of patients with HCC.
The positivity rate in patients with HCC for the combination of Ln-gamma2 and DCP
was 89.5%, which was better than that for either of the two markers alone (63%
and 68%, respectively). Among patients with early-stage HCC (T1 or T2), the
positivity rates for monomeric Ln-gamma2, AFP and DCP were 61%, 39% and 57%,
respectively. Serum Ln-gamma2 may be a potential biomarker for HCC surveillance.
The combination of Ln-gamma2 and DCP may be more sensitive for laboratory
diagnosis of HCC than the combination of AFP and DCP.
PMID- 28418228
TI - Probiotics-impregnated bedding covers for house dust mite allergic rhinitis: A
pilot randomized clinical trial.
PMID- 28418230
TI - Corrigendum for Blonder et al. (2017) DOI: 10.1111/ele.12736.
PMID- 28418229
TI - Assembly of a Benzo-Fused Bridged Ketone Scaffold from 1,5,10-Enediynes through
One-Pot Ruthenium-Catalyzed Cyclization/Iodine-Mediated Oxidative Ring Expansion.
AB - In the presence of a cationic Ru catalyst, 1,6-diynes bearing a terminal styryl
moiety underwent [2+2+2] cyclization to produce dehydrobiphenylenes fused with a
five-membered ring. Although the cycloadducts were unstable toward purification,
their one-pot iodine-mediated ring expansion successfully afforded unprecedented
bridged ketone products containing a benzo-fused bicyclo[3.2.1] framework.
PMID- 28418231
TI - A Dendritic Amphiphile for Efficient Control of Biomimetic Calcium Phosphate
Mineralization.
AB - The phase behavior of a dendritic amphiphile containing a Newkome-type dendron as
the hydrophilic moiety and a cholesterol unit as the hydrophobic segment is
investigated at the air-liquid interface. The amphiphile forms stable
monomolecular films at the air-liquid interface on different subphases.
Furthermore, the mineralization of calcium phosphate beneath the monolayer at
different calcium and phosphate concentrations versus mineralization time shows
that at low calcium and phosphate concentrations needles form, whereas flakes and
spheres dominate at higher concentrations. Energy-dispersive X-ray spectroscopy,
X-ray photoelectron spectroscopy, and electron diffraction confirm the formation
of calcium phosphate. High-resolution transmission electron microscopy and
electron diffraction confirm the predominant formation of octacalcium phosphate
and hydroxyapatite. The data also indicate that the final products form via a
complex multistep reaction, including an association step, where nano-needles
aggregate into larger flake-like objects.
PMID- 28418233
TI - In Situ Expanding Pores of Dodecahedron-like Carbon Frameworks Derived from MOFs
for Enhanced Capacitive Deionization.
AB - The pores of dodecahedron-like carbon frameworks derived from metal-organic
frameworks (MOFs) were in situ expanded via a surfactant-template strategy, which
were originally demonstrated to enhance capacitive deionization (CDI). The
dodecahedron-like carbon frameworks were obtained through carbonization of
zeolitic imidazolate framework-8 (ZIF-8) using the cetyltrimethylammonium bromide
as a supramolecular template. It is found that the dodecahedron-like carbon
frameworks derived from ZIF-8 possess efficiently expanded pores while retaining
the original morphology and high nitrogen contents. Compared to those of the
normal ZIF-8-derived carbon, the obtained materials exhibit a hierarchically
porous structure with a higher specific surface area and an improved pore volume.
Electrochemical studies of the obtained electrode demonstrate that this material
has a high specific capacitance and lower inner resistance. More importantly, the
obtained material shows a higher salt adsorption capacity (20.05 mg/g) than the
normal ZIF-8-derived carbon (13.01 mg/g). Furthermore, the obtained electrode
presents a rapid salt removal rate and excellent cycling stability. The
significantly enhanced deionization behavior of the obtained materials is due to
the combination effect of its large accessible surface area, large pore volume,
and rich nitrogen doping. The results reveal that in situ expanding pores of
carbon frameworks derived from MOFs is an ideal way for constructing electrode
materials with enhanced CDI performance. The present work may pave a path for the
design and development of highly efficient MOF-derived electrode materials.
PMID- 28418232
TI - High pre-exposure prophylaxis uptake and early adherence among men who have sex
with men and transgender women at risk for HIV Infection: the PrEP Brasil
demonstration project.
AB - INTRODUCTION: The efficacy of pre-exposure prophylaxis (PrEP) in preventing
sexual acquisition of human immunodeficiency virus (HIV) is well established.
Little is known about the feasibility of PrEP implementation in middle-income
settings with concentrated epidemics among men who have sex with men (MSM) and
transgender women (TGW). METHODS: PrEP Brasil is a prospective, multicentre, open
label demonstration project assessing PrEP delivery in the context of the
Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres
in Rio de Janeiro and Sao Paulo were evaluated for eligibility and offered 48
weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir
diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early
adherence) were measured. Predictors of drug levels were assessed using ordinal
logistic regression models considering the DBS drug level as a 3 level variable
(<350 fmol/punch, >=350-699 fmol/punch and >=700 fmol/punch). RESULTS: 1,270
individuals were assessed for participation; n = 738 were potentially eligible
and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled
individuals were younger, had lower HIV risk perception and had lower PrEP
awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP
concentrations, 94.1% in the protective range (>=350 fmol/punch, consistent with
>=2 pills per week), and 78% were in the highly protective range (>=700
fmol/punch, >=4 pills per week). Participants with >=12 years of schooling had
1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than
participants with <12 years of schooling. Condomless receptive anal intercourse
in the prior 3 months was also associated with higher drug levels (adjusted OR =
1.78; 95% CI 1.08-2.94). CONCLUSION: The high uptake and early adherence indicate
that PrEP for high-risk MSM and TGW can be successfully delivered in the context
of the Brazilian Public Health System. Interventions to address disparities on
PrEP awareness and HIV risk perception among the younger and less educated are
urgently needed in order to maximize the impact of this prevention strategy on
the reduction of HIV infection among MSM and TGW in Brazil.
PMID- 28418234
TI - Piezoresistive Effect in Plasma-Doping of Graphene Sheet for High-Performance
Flexible Pressure Sensing Application.
AB - This paper presents a straightforward plasma treatment modification of graphene
with an enhanced piezoresistive effect for the realization of a high-performance
pressure sensor. The changes in the graphene in terms of its morphology,
structure, chemical composition, and electrical properties after the NH3/Ar
plasma treatment were investigated in detail. Through a sufficient plasma
treatment condition, our studies demonstrated that plasma-treated graphene sheet
exhibits a significant increase in sensitivity by one order of magnitude compared
to that of the unmodified graphene sheet. The plasma-doping introduced nitrogen
(N) atoms inside the graphene structure and was found to play a significant role
in enhancing the pressure sensing performance due to the tunneling behavior from
the localized defects. The high sensitivity and good robustness demonstrated by
the plasma-treated graphene sensor suggest a promising route for simple, low
cost, and ultrahigh resolution flexible sensors.
PMID- 28418235
TI - Discovery of the Showdomycin Gene Cluster from Streptomyces showdoensis ATCC
15227 Yields Insight into the Biosynthetic Logic of C-Nucleoside Antibiotics.
AB - Nucleoside antibiotics are a large class of pharmaceutically relevant chemical
entities, which exhibit a broad spectrum of biological activities. Most
nucleosides belong to the canonical N-nucleoside family, where the heterocyclic
unit is connected to the carbohydrate through a carbon-nitrogen bond. However,
atypical C-nucleosides were isolated from Streptomyces bacteria over 50 years
ago, but the molecular basis for formation of these metabolites has been unknown.
Here, we have sequenced the genome of S. showdoensis ATCC 15227 and identified
the gene cluster responsible for showdomycin production. Key to the detection was
the presence of sdmA, encoding an enzyme of the pseudouridine monophosphate
glycosidase family, which could catalyze formation of the C-glycosidic bond.
Sequence analysis revealed an unusual combination of biosynthetic genes, while
inactivation and subsequent complementation of sdmA confirmed the involvement of
the locus in showdomycin formation. The study provides the first steps toward
generation of novel C-nucleosides by pathway engineering.
PMID- 28418236
TI - Novel Approach of Using Near-Infrared Responsive PEGylated Gold Nanorod Coated
Poly(l-lactide) Microneedles to Enhance the Antitumor Efficiency of Docetaxel
Loaded MPEG-PDLLA Micelles for Treating an A431 Tumor.
AB - The combination of chemotherapy and photothermal therapy (PTT) plays a
significant role in synergistic tumor therapy. However, a high dosage of
chemotherapy drugs or photothermal agents may cause series side effects. To
overcome these challenges, we designed a near-infrared (NIR) responsive PEGylated
gold nanorod (GNR-PEG) coated poly(l-lactide) microneedle (PLLA MN) system (GNR
PEG@MN) to enhance antitumor efficiency of docetaxel-loaded MPEG-PDLLA (MPEG
PDLLA-DTX) micelles for treating an A431 tumor. The as-made GNR-PEG@MNs contained
only 31.83 +/- 1.22 MUg of GNR-PEG per patch and exhibited excellent heating
efficacy both in vitro and in vivo. Meanwhile, GNR-PEG@MN with the height of 480
MUm had good skin insertion ability and was harmless to the skin. On the other
hand, GNR-PEG@MN had good heating transfer ability in vivo, and the tumor sites
could reach 50 degrees C within 5 min. In comparison with chemotherapy and PTT
alone, the combination of low dosage MPEG-PDLLA-DTX micelles (5 mg/kg) and GNR
PEG@MNs completely eradicated the A431 tumor without recurrence in vivo,
demonstrating a remarkable synergetic effect. Hence, GNR-PEG@MN could be a
promising carrier to enhance the antitumor effect of MPEG-PDLLA-DTX micelles for
treating superficial tumors and is expected to have a great potential in clinical
translation for human epidermoid cancer therapy.
PMID- 28418238
TI - Specific and Differential Binding of N-Acetylgalactosamine Glycopolymers to the
Human Macrophage Galactose Lectin and Asialoglycoprotein Receptor.
AB - A range of glycopolymers composed of N-acetylgalactosamine were prepared via
sequential Cu(I)-mediated polymerization and alkyne-azide click (CuAAC). The
resulting polymers were shown, via multichannel surface plasmon resonance, to
interact specifically with human macrophage galactose lectin (MGL; CD301) with
high affinity (KD = 1.11 MUM), but they did not bind to the mannose/fucose
selective human lectin dendritic-cell-specific intercellular adhesion molecule-3
grabbing nonintegrin (DC-SIGN; CD209). The effect of sugar ligand valency on the
binding (so-called "glycoside cluster effect") of poly(N-acetylgalactosamine) to
MGL was investigated by varying first the polymer chain length (DP: 100, 64, 40,
23, 12) and then the architecture (4- and 8-arm star glycopolymers). The chain
length did not have a significant effect on the binding to MGL (KD = 0.17-0.52
MUM); however, when compared to a hepatic C-type lectin of a similar
monosaccharide specificity, the asialoglycoprotein receptor (ASGPR), the binding
affinity was more noticeably affected (KD = 0.37- 6.65 MUM). These data suggest
that known differences in the specific configuration/orientation of the
carbohydrate recognition domains of MGL and ASGPR are responsible for the
differences in binding observed between the different polymers of varied chain
length and architecture. In the future, this model has the potential to be
employed for the development of tissue-selective delivery systems.
PMID- 28418237
TI - What Gene Mutations Affect Serotonin in Mice?
AB - Although serotonin neurotransmission has been implicated in several
neurodevelopmental and psychological disorders, the factors that drive
dysfunction of the serotonin system are poorly understood. Current research
regarding the serotonin system revolves around its dysfunction in
neuropsychiatric disorders, but there is no database collating genetic mutations
that result in serotonin abnormalities. To bridge this gap, we developed a list
of genes in mice that, when perturbed, result in altered levels of serotonin
either in brain or blood. Due to the intrinsic limitations of search, the current
list should be considered a preliminary subset of all relevant cases.
Nevertheless, it offered an opportunity to gain insight into what types of genes
have the potential to impact serotonin by using gene ontology (GO). This analysis
found that genes associated with monoamine metabolism were more often associated
with increases in brain serotonin than decreases. Speculatively, this could be
because several pathways (and therefore many genes) are responsible for the
clearance and metabolism of serotonin whereas only one pathway (and therefore
fewer genes) is directly involved in the synthesis of serotonin. Another
contributor could be cross talk between monoamine systems such as dopamine. In
contrast, genes that were associated with decreases in brain serotonin were more
likely linked to a developmental process. Sensitivity of serotonin neurons to
developmental perturbations could be due to their complicated neuroanatomy or
possibly they may be negatively regulated by dysfunction of their innervation
targets. Thus, these observations suggest hypotheses regarding the mechanisms
underlying the vulnerability of brain serotonin neurotransmission.
PMID- 28418239
TI - Oxygen Vacancy Associated Surface Fenton Chemistry: Surface Structure Dependent
Hydroxyl Radicals Generation and Substrate Dependent Reactivity.
AB - Understanding the chemistry of hydrogen peroxide (H2O2) decomposition and
hydroxyl radical (*OH) transformation on the surface molecular level is a great
challenge for the application of heterogeneous Fenton system in the fields of
chemistry, environmental, and life science. We report in this study a conceptual
oxygen vacancy associated surface Fenton system without any metal ions leaching,
exhibiting unprecedented surface chemistry based on the oxygen vacancy of
electron-donor nature for heterolytic H2O2 dissociation. By controlling the
delicate surface structure of catalyst, this novel Fenton system allows the
facile tuning of *OH existing form for targeted catalytic reactions with
controlled reactivity and selectivity. On the model catalyst of BiOCl, the
generated *OH tend to diffuse away from the (001) surface for the selective
oxidation of dissolved pollutants in solution, but prefer to stay on the (010)
surface, reacting with strongly adsorbed pollutants with high priority. These
findings will extend the scope of Fenton catalysts via surface engineering and
consolidate the fundamental theories of Fenton reactions for wide environmental
applications.
PMID- 28418240
TI - Enzymatic Carbon-Sulfur Bond Formation in Natural Product Biosynthesis.
AB - Sulfur plays a critical role for the development and maintenance of life on
earth, which is reflected by the wealth of primary metabolites, macromolecules,
and cofactors bearing this element. Whereas a large body of knowledge has existed
for sulfur trafficking in primary metabolism, the secondary metabolism involving
sulfur has long been neglected. Yet, diverse sulfur functionalities have a major
impact on the biological activities of natural products. Recent research at the
genetic, biochemical, and chemical levels has unearthed a broad range of enzymes,
sulfur shuttles, and chemical mechanisms for generating carbon-sulfur bonds. This
Review will give the first systematic overview on enzymes catalyzing the
formation of organosulfur natural products.
PMID- 28418241
TI - Unique Ruthenium Bimetallic Supramolecular Cages From C4-Symmetric Tetrapyridyl
Metalloligands.
AB - The self-assembly of C4-symmetric tetrapyridyl metalloligands containing Fe or Co
and diruthenium electron acceptors by means of dative coordination bonding led to
the formation of six different heterobimetallic supramolecules. All complexes
were characterized by X-ray crystallography, ESI mass spectrometry, and 1H NMR
(in the case of diamagnetic systems) spectroscopy. The bridging units in the
diruthenium complexes greatly influenced the geometrical preference of the
supramolecular structures, resulting in the formation of different architectures,
namely A4D2 or A6D3 (A = acceptor, D = donor). Depending on the bridging unit,
A4D2 tetragonal prism, A4D2 molecular tweezer, or A6D3 triple-decker complexes
were obtained selectively. The self-assembly of an unexpected triple-decker type
Ru12Fe3 heterobimetallic species was also observed.
PMID- 28418243
TI - General Approach toward Aspidospermatan-Type Alkaloids Using One-Pot Vilsmeier
Haack Cyclization and Azomethine Ylide Cycloaddition.
AB - The development of a new one-pot reaction sequence afforded the tricyclic core of
several aspidospermatan-type alkaloids from a linear, densely functionalized
substrate. The key sequence features a highly chemoselective formamide activation
that triggered a Vilsmeier-Haack cyclization, followed by an azomethine ylide
generation and intramolecular cycloaddition. The choice of nucleophile,
azomethine ylide precursor, and dipolarophile was crucial to the success of the
sequence.
PMID- 28418244
TI - Applying Bayesian Approach to Combinatorial Problem in Chemistry.
AB - A Bayesian optimization procedure, in combination with density functional theory
calculations, was applied to a combinatorial problem in chemistry. As a specific
example, we examined the stable structures of lithium-graphite intercalation
compounds (Li-GICs). We found that this approach efficiently identified the
stable structure of stage-I and -II Li-GICs by calculating 4-6% of the full
search space. We expect that this approach will be helpful in solving problems in
chemistry that can be regarded as a kind of combinatorial problem.
PMID- 28418242
TI - Slow but Steady Wins the Race: Dissimilarities among New Dual Inhibitors of the
Wild-Type and the V27A Mutant M2 Channels of Influenza A Virus.
AB - New insights on the amantadine resistance mechanism of the V27A mutant were
obtained through the study of novel, easily accessible 4-(1- and 2
adamantyl)piperidines, identified as dual binders of the wild-type and V27A
mutant M2 channels of influenza A virus. Their antiviral activity and channel
blocking ability were determined using cell-based assays and two-electrode
voltage clamp (TEVC) technique on M2 channels, respectively. In addition,
electrophysiology experiments revealed two interesting findings: (i) these
inhibitors display a different behavior against the wild-type versus V27A mutant
A/M2 channels, and (ii) the compounds display antiviral activity when they have
kd equal or smaller than 10-6 while they do not exhibit antiviral activity when
kd is 10-5 or higher although they may show blocking activity in the TEV assay.
Thus, caution must be taken when predicting antiviral activity based on percent
channel blockage in electrophysiological assays. These findings provide
experimental evidence of the resistance mechanism of the V27A mutation to wild
type inhibitors, previously predicted in silico, offer an explanation for the
lack of antiviral activity of compounds active in the TEV assay, and may help
design new and more effective drugs.
PMID- 28418245
TI - Geranylpyrrol A and Piericidin F from Streptomyces sp. CHQ-64 DeltardmF.
AB - Two new compounds, geranylpyrrol A (1) and piericidin F (2), were isolated from a
reedsmycins nonproducing mutant strain of Streptomyces sp. CHQ-64. Their
structures, including absolute configurations, were elucidated by extensive NMR,
MS, NOESY, and ECD analyses. Geranylpyrrol A (1) is an unusual naturally
occurring 2,3,4-trisubstituted pyrrole, and piericidin F (2) showed cytotoxicity
against HeLa, NB4, A549, and H1975 cell lines with IC50 values of 0.003, 0.037,
0.56, and 0.49 MUM, respectively.
PMID- 28418246
TI - Water-Ice Analogues of Polycyclic Aromatic Hydrocarbons: Water Nanoclusters on
Cu(111).
AB - Water has an incredible ability to form a rich variety of structures, with 16
bulk ice phases identified, for example, as well as numerous distinct structures
for water at interfaces or under confinement. Many of these structures are built
from hexagonal motifs of water molecules, and indeed, for water on metal
surfaces, individual hexamers of just six water molecules have been observed.
Here, we report the results of low-temperature scanning tunneling microscopy
experiments and density functional theory calculations which reveal a host of new
structures for water-ice nanoclusters when adsorbed on an atomically flat Cu
surface. The H-bonding networks within the nanoclusters resemble the resonance
structures of polycyclic aromatic hydrocarbons, and water-ice analogues of inene,
naphthalene, phenalene, anthracene, phenanthrene, and triphenylene have been
observed. The specific structures identified and the H-bonding patterns within
them reveal new insight about water on metals that allows us to refine the so
called "2D ice rules", which have so far proved useful in understanding water-ice
structures at solid surfaces.
PMID- 28418247
TI - High and Stable Ionic Conductivity in 2D Nanofluidic Ion Channels between Boron
Nitride Layers.
AB - Achieving a high rate of ionic transport through porous membranes and ionic
channels is important in numerous applications ranging from energy storage to
water desalination, but it still remains a challenge. Herein we show that ions
can quickly pass through interlayer spaces in hydrated boron nitride (BN)
membranes. Measurements of surface-charge governed ionic currents between BN
nanosheets in a variety of salt solutions (KCl, NaCl and CaCl2) at low salt
concentrations (<10-4 M) showed several orders of magnitude higher ionic
conductivity compared to that of the bulk solution. Moreover, due to the
outstanding chemical and thermal stability of BN, the ionic conduits remain fully
functional at temperatures up to 90 degrees C. The BN conduits can operate in
acidic and basic environments and do not degrade after immersing in solutions
with extreme pH (pH ~ 0 or 14) for 1 week. Those excellent properties make the BN
ionic conduits attractive for applications in nanofluidic devices and membrane
separation.
PMID- 28418248
TI - Total Synthesis, Configuration Assignment, and Cytotoxic Activity Evaluation of
Protulactone A.
AB - The first total synthesis and absolute configuration assignment of protulactone A
(1) has been achieved. Four stereoisomers, 1a, ent-1a, 1b, and ent-1b, of this
natural polyketide were prepared by chiral pool synthesis starting from l- and d
arabinose, respectively. The absolute and relative configurations of all isomers
were assigned by single-crystal X-ray analysis. Target compounds were screened
for their in vitro cytotoxicity toward certain human tumor cells (NCI60 cancer
cell line panel).
PMID- 28418249
TI - beta-Hydride Elimination and C-H Activation by an Iridium Acetate Complex,
Catalyzed by Lewis Acids. Alkane Dehydrogenation Cocatalyzed by Lewis Acids and
[2,6-Bis(4,4-dimethyloxazolinyl)-3,5-dimethylphenyl]iridium.
AB - NaBArF4 (sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate) was found to
catalyze reactions of (Phebox)IrIII(acetate) (Phebox = 2,6-bis(4,4
dimethyloxazolinyl)-3,5-dimethylphenyl) complexes, including (i) beta-H
elimination of (Phebox)Ir(OAc)(n-alkyl) to give (Phebox)Ir(OAc)(H) and the
microscopic reverse, alkene insertion into the Ir-H bond of (Phebox)Ir(OAc)(H),
and (ii) hydrogenolysis of the Ir-alkyl bond of (Phebox)Ir(OAc)(n-alkyl) and the
microscopic reverse, C-H activation by (Phebox)Ir(OAc)(H), as indicated by H/D
exchange experiments. For example, beta-H elimination of (Phebox)Ir(OAc)(n-octyl)
(2-Oc) proceeded on a time scale of minutes at -15 degrees C in the presence of
(0.4 mM) NaBArF4 as compared with a very slow reaction at 125 degrees C in the
absence of NaBArF4. In addition to NaBArF4, other Lewis acids are also effective.
Density functional theory calculations capture the effect of the Na+ cation and
indicate that it operates primarily by promoting kappa2-kappa1 dechelation of the
acetate anion, which opens the coordination site needed to allow the observed
reaction to proceed. In accord with the effect on these individual stoichiometric
reactions, NaBArF4 was also found to cocatalyze, with (Phebox)Ir(OAc)(H), the
acceptorless dehydrogenation of n-dodecane.
PMID- 28418250
TI - Identifying the Active Surfaces of Electrochemically Tuned LiCoO2 for Oxygen
Evolution Reaction.
AB - Identification of active sites for catalytic processes has both fundamental and
technological implications for rational design of future catalysts. Herein, we
study the active surfaces of layered lithium cobalt oxide (LCO) for the oxygen
evolution reaction (OER) using the enhancement effect of electrochemical
delithiation (De-LCO). Our theoretical results indicate that the most stable
(0001) surface has a very large overpotential for OER independent of lithium
content. In contrast, edge sites such as the nonpolar (1120) and polar (0112)
surfaces are predicted to be highly active and dependent on (de)lithiation. The
effect of lithium extraction from LCO on the surfaces and their OER activities
can be understood by the increase of Co4+ sites relative to Co3+ and by the shift
of active oxygen 2p states. Experimentally, it is demonstrated that LCO
nanosheets, which dominantly expose the (0001) surface show negligible OER
enhancement upon delithiation. However, a noticeable increase in OER activity
(~0.1 V in overpotential shift at 10 mA cm-2) is observed for the LCO
nanoparticles, where the basal plane is greatly diminished to expose the edge
sites, consistent with the theoretical simulations. Additionally, we find that
the OER activity of De-LCO nanosheets can be improved if we adopt an acid etching
method on LCO to create more active edge sites, which in turn provides a strong
evidence for the theoretical indication.
PMID- 28418251
TI - Enantio- and Diastereoselective Nitro-Mannich Reaction of alpha-Aryl
Nitromethanes with Amidosulfones Catalyzed by Phase-Transfer Catalysts.
AB - A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of
alpha-aryl nitromethanes with amidosulfones catalyzed by a novel chiral phase
transfer catalyst, bearing multiple H-bonding donors, derived from quinine was
developed. A variety of alpha-aryl nitromethanes and amidosulfones were
investigated; and the corresponding products were obtained in excellent yields
with excellent diastereo- and enantioselectivities (up to 99% yield, > 99:1 dr
and >99% ee). As a demonstration of synthetic utility, the resulting beta
nitroamines could be converted to corresponding meso-symmetric and optically pure
unsymmetric anti-1,2-diarylethylenediamines.
PMID- 28418252
TI - Electronic and Structural Study of ZnxSx [x = 12, 16, 24, 28, 36, 48, 96, and
108] Cage Structures.
AB - We present a density functional study on the structural and electronic properties
of ZnS bubble clusters, specifically, hollow cages whose spontaneous formation
was previously observed in classical molecular dynamics simulations by Spano et
al. [J. Phys. Chem. B 2003, 107, 10337]. The hollow ZnS cages in our study were
modeled as ZnxSx [x = 12, 16, 24, 28, 36, 48, 108], and an onionlike structure
was modeled as Zn96S96. The study of energetics and stability, performed using
large polarized Gaussian basis sets, indicated all structures to be energetically
stable with similar binding energy of 5.5-5.6 eV per ZnS pair. Further
computation of electronic properties showed that these cages have large vertical
ionization energies and relatively low electron affinities in the ranges of 6.8
8.1 and 1.7-3.0 eV, respectively. They have large highest occupied molecular
orbital-lowest unoccupied molecular orbital gaps between 2.5 and 3.3 eV, and
quasi-particle gaps vary from 6.2 eV for Zn12S12 to 4.19 for Zn108S108. The
computed vibrational frequencies for selected cages, that is, Zn12S12, Zn16S16,
Zn28S28 (O, S4, and S8 point groups), and Zn36S36 indicate that these cage
structures correspond to local minima on the potential energy surface. Finally,
the infrared spectra calculated using large basis sets are also reported.
PMID- 28418253
TI - Species-Level Discrimination of Psychrotrophic Pathogenic and Spoilage Gram
Negative Raw Milk Isolates Using a Combined MALDI-TOF MS Proteomics
Bioinformatics-based Approach.
AB - Identification of psychrotrophic pathogenic and spoilage Gram-negative bacteria
using rapid and reliable techniques is important in commercial milk processing,
as these bacteria can produce heat-resistant proteases and act as postprocessing
contaminants in pasteurized milk. Matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry (MALDI-TOF MS) is a proven technology for
identification of bacteria in food, however, may require optimization for
identification of pathogenic and spoilage bacteria in milk and dairy products.
The current study evaluated the effects of various culture conditions and sample
preparation methods on assigning of raw milk isolates to the species level by
MALDI-TOF MS. The results indicated that culture media, incubation conditions
(temperature and time), and sample preparation significantly affected the
identification rates of bacteria to the species level. Nevertheless, the
development of spectral libraries of isolates grown on different media using a
web tool for hierarchical clustering of peptide mass spectra (SPECLUST) followed
by a ribosomal protein based bioinformatics approach significantly enhanced the
assigning of bacteria, with at least one unique candidate biomarker peak
identified for each species. Phyloproteomic relationships based on spectral
profiles were compared to phylogenetic analysis using 16S rRNA gene sequences and
demonstrated similar clustering patterns with significant discriminatory power.
Thus, with appropriate optimization, MALDI-TOF MS is a valuable tool for species
level discrimination of pathogenic and milk spoilage bacteria.
PMID- 28418254
TI - Evaluating the Characteristics of Reporter Ion Signal Acquired in the Orbitrap
Analyzer for Isobaric Mass Tag Proteome Quantification Experiments.
AB - Multiplexed quantification with isobaric chemical tags (e.g., TMT, iTRAQ)
provides a robust and efficient means to comparatively examine proteome dynamics
between several biological states using a mass spectrometer (MS). The
quantitative nature of isobaric tags necessitates strict validation of the
observed ion signals in the chosen MS detector before differential patterns are
extracted between biological states. We present an in-depth analysis of isobaric
tag data acquired on current generation Orbitrap MS hardware to illustrate
pitfalls in acquisition settings that can negatively impact results. We
establish, for the first time, the presence of a notch, a region of no observed
values, in the reporter ion distributions from isobaric-labeled peptide mixtures
acquired on these instruments. We determine that this notch is present in
published data across a wide range of instruments of the same or different type
and is isolated to the Orbitrap mass analyzer. We demonstrate that the impact of
the notch can be minimized using manipulations of Orbitrap scan parameters and on
column injection amounts. Lastly, using a mixture of synthetic standard peptides
we investigated the impact on identification rates and quantification precision.
Together, these data highlight an important phenomenon that negatively impacts
peptide identification and quantification in the Orbitrap analyzer as well as
outlining guidelines to follow to ensure minimization of MS-induced artifacts in
isobaric tag experiments resulting from the notch.
PMID- 28418255
TI - Transient Clustering of Reaction Intermediates during Wet Etching of Silicon
Nanostructures.
AB - Wet chemical etching is a key process in fabricating silicon (Si) nanostructures.
Currently, wet etching of Si is proposed to occur through the reaction of surface
Si atoms with etchant molecules, forming etch intermediates that dissolve
directly into the bulk etchant solution. Here, using in situ transmission
electron microscopy (TEM), we follow the nanoscale wet etch dynamics of amorphous
Si (a-Si) nanopillars in real-time and show that intermediates generated during
alkaline wet etching first aggregate as nanoclusters on the Si surface and then
detach from the surface before dissolving in the etchant solution. Molecular
dynamics simulations reveal that the molecules of etch intermediates remain
weakly bound to the hydroxylated Si surface during the etching and aggregate into
nanoclusters via surface diffusion instead of directly diffusing into the etchant
solution. We confirmed this model experimentally by suppressing the formation of
nanoclusters of etch intermediates on the Si surfaces by shielding the
hydroxylated Si sites with large ions. These results suggest that the interaction
of etch intermediates with etching surfaces controls the solubility of reaction
intermediates and is an important parameter in fabricating densely packed clean
3D nanostructures for future generation microelectronics.
PMID- 28418256
TI - Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four
Stereoisomers of Sphinganine.
AB - All four stereoisomers of sphinganine can be synthesized by a multicomponent
aziridination of an aldehyde, an amine and an alpha-diazo carbonyl compound
mediated by a BOROX catalyst with high asymmetric induction (>=96% ee). The threo
isomers are available from ring-opening of cis-aziridines by an oxygen
nucleophile with inversion at the C-3 position and the erythro-isomers are
likewise available from trans-aziridines.
PMID- 28418257
TI - Investigating Acquisition Performance on the Orbitrap Fusion When Using Tandem
MS/MS/MS Scanning with Isobaric Tags.
AB - Methods for isobaric-tagged peptide analysis (e.g., TMT, iTRAQ), such as the
synchronous precursor selection (SPS) tandem MS/MS/MS (MS3) approach, enable
maintenance of reporter ion accuracy and precision by reducing the ratio
compression caused by coisolated precursor ions. However, the decreased
throughput of the MS3 approach necessitates careful optimization of acquisition
strategies and methods to ensure maximal proteome coverage. We present a
systematic analysis of acquisition parameters used to analyze isobaric-tagged
peptide samples on current generation Orbitrap mass spectrometer (MS) hardware.
In contrast with previously reported works, we demonstrate the limited utility of
acquiring reporter ion data in the ion trap analyzer; ion trap acquisition had
only a minimal increase in identification depth and reduced quantification
precision. We establish that despite the significantly increased scan rate
afforded through the use of higher energy collisional dissociation (HCD) in MS3
based ion trap isobaric tag analyses, the reduced quantification precision and
reporter ion yields negate the potential benefits in proteome coverage. Lastly,
using optimized parameter sets, we further demonstrate the limited utility of the
ion trap detector versus the Orbitrap for reporter ion detection in an in-depth
analysis of a complex proteome sample. Together, these data will serve as a
valuable resource to researchers undertaking analysis on current generation
Orbitrap instrumentation with isobaric tags.
PMID- 28418258
TI - High Thermoelectric Performance in Electron-Doped AgBi3S5 with Ultralow Thermal
Conductivity.
AB - We report electron-doped AgBi3S5 as a new high-performance nontoxic
thermoelectric material. This compound features exceptionally low lattice thermal
conductivities of 0.5-0.3 W m-1 K-1 in the temperature range of 300-800 K, which
is ascribed to its unusual vibrational properties: "double rattling" phonon modes
associated with Ag and Bi atoms. Chlorine doping at anion sites acts as an
efficient electron donor, significantly enhancing the electrical properties of
AgBi3S5. In the carrier concentration range (5 * 1018-2 * 1019 cm-3) investigated
in this study, the trends in Seebeck coefficient can be reasonably understood
using a single parabolic band model with the electron effective mass of 0.22 me
(me is the free electron mass). Samples of 0.33% Cl-doped AgBi3S5 prepared by
spark plasma sintering show a thermoelectric figure of merit of ~1.0 at 800 K.
PMID- 28418259
TI - Signature of Congregated Effects of Mechanical and Electrical Anharmonicities,
Fermi Resonances, and Dampings on the IR Spectra of Hydrogen Bonded Systems:
Quantum Dynamic Study.
AB - Theoretical IR spectral density of the high-frequency stretching mode of hydrogen
bond (H-bond) systems is reported using a three-dimensional approach. The model,
studied within the framework of linear response theory, involves the mechanical
anharmonicity of the high-frequency stretching mode by contemplating its
potential as an asymmetric double well potential, the mechanical anharmonicity of
the H-bond Bridge by contemplating its potential as a Morse potential, Fermi
resonances which occur between the high frequency stretching mode and the
overtones of the bending modes, the electrical anharmonicity translated by the
nonlinearity to second order in the electric dipole moment function of the fast
mode, the second order modulation of the angular frequency and the equilibrium
position of the fast mode on the slow mode coordinate, and direct and indirect
relaxation mechanism. Moreover, the repulsive potential interposing in the fast
mode potential is chosen in Gaussian form to account for the asymmetry of the
fast mode potential and thereby elucidate the nature of the H-bond. The
anharmonic coupling between the fast and slow frequency modes is handled within
the strong anharmonic coupling theory. The direct relaxation of the fast mode and
the indirect relaxation of the H-bond Bridge are consolidated using previous
results [Rekik et al. Chem. Phys. 2008, 352, 65-76]. The infrared spectral
density is calculated using the Fourier transform of the autocorrelation function
of the transition dipole moment operator of the fast mode. The evolution of the
infrared absorption is demonstrated, indicating that mixing of all these effects
results in a broadening and complicated distribution of the spectral density. The
result of this work underscores the necessity of simultaneously combining the
maximum effects in H-bonded complexes for effectively modeling and interpreting
their corresponding IR spectra.
PMID- 28418260
TI - Fine Tuning of Multicolored Photoluminescence in Crystalline Magnetic Materials
Constructed of Trimetallic EuxTb1-x[Co(CN)6] Cyanido-Bridged Chains.
AB - Coordination compounds built of trivalent lanthanide ions have been demonstrated
as promising solid-state materials for diverse photoluminescent applications and
as attractive magnetic objects with the prospective application in information
storage and spintronics. We present a synthetic methodology in which both
luminescent and magnetic functionalities are induced within lanthanide-based
coordination polymers by the application of hexacyanocobaltate(III) anions and 3
hydroxypyridine (3-OHpy), both coordinated to 4f-metal ions modulating the
lanthanide-centered properties. We report a series of trimetallic cyanido-bridged
chains {[EuIIIxTbIII1-x(3-OHpy)2(H2O)4][CoIII(CN)6]}.H2O (x = 1, 0.8, 0.5, 0.4,
0.3, 0.2, 0.1, 0; compounds 1, 2, ..., 7, 8). They reveal tunable visible
photoluminescence ranging from green, through yellow and orange, to red color
depending on the composition of material and the wavelength of UV excitation
light. Such multicolored emission is realized by the adjusted ratio between red
emissive Eu3+ and green emissive Tb3+ and by the selection of wavelengths of UV
light controlling the intensities of Eu- and Tb-based components of visible
luminescence. The photoluminescence is enhanced by the energy-transfer (ET)
process from [CoIII(CN)6]3- and 3-OHpy to lanthanides, and the efficiencies of ET
to Eu and Tb play an important role in the switchable emission. The whole family,
1-8, exhibits temperature-dependent paramagnetism due to the intrinsic property
of lanthanide(3+) ions. Tb-containing 2-8 reveal the field-induced slow
relaxation of magnetization due to the magnetic anisotropy of Tb3+. Moreover, the
compounds built of large amounts of Tb reveal the double relaxation, the faster
of a typical TbIII single-ion origin, and the slower originating from the
magnetic dipole-magnetic dipole interactions between neighboring TbIII centers.
Compound 2, which can be considered as a magnetically diluted sample, exhibits
almost single relaxation process with the thermal energy barrier DeltaE/kB of
35.8(6) K and tau0 = 1.1(2) * 10-8 s at Hdc = 1500 Oe, indicating a single
molecule magnet behavior.
PMID- 28418261
TI - Preschool children's communication, motor and social development: Parents' and
educators' concerns.
AB - PURPOSE: During early childhood, it is important to identify which children
require intervention before they face the increased demands of school. This study
aimed to: (1) compare parents' and educators' concerns, (2) examine inter-rater
reliability between parents' and educators' concerns and (3) determine the group
difference between level of concern and children's performance on clinical
testing. METHOD: Parents and educators of 1205 4- to 5-year-old children in the
Sound Start Study completed the Parents' Evaluation of Developmental Status.
Children whose parents/educators were concerned about speech and language
underwent direct assessment measuring speech accuracy (n = 275), receptive
vocabulary (n = 131) and language (n = 274). RESULT: More parents/educators were
concerned about children's speech and expressive language, than behaviour, social
emotional, school readiness, receptive language, self-help, fine motor and gross
motor skills. Parents' and educators' responses were significantly correlated
(except gross motor). Parents' and educators' level of concern about expressive
speech and language was significantly correlated with speech accuracy on direct
assessment. Educators' level of concern was significantly correlated with a
screening measure of language. Scores on a test of receptive vocabulary
significantly differed between those with concern and those without. CONCLUSION:
Children's communication skills concerned more parents and educators than other
aspects of development and these concerns generally aligned with clinical
testing.
PMID- 28418262
TI - Adherence and persistence in patients with type 2 diabetes mellitus newly
initiating canagliflozin, dapagliflozin, dpp-4s, or glp-1s in the United States.
AB - OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors were first approved in the
US in 2013; therefore, real-world (RW) studies describing outcomes are limited.
This retrospective study evaluated adherence and persistence among patients
initiating canagliflozin (CANA), dapagliflozin (DAPA), GLP-1 agonists (GLP-1s),
and DPP-4 inhibitors (DPP-4s) over a 12-month follow-up from a US managed care
perspective. METHODS: Patients newly initiating CANA, DAPA, GLP-1s, or DPP-4s
from February 1, 2014-June 30, 2014 were identified from the QuintilesIMS
PharMetrics Plus Database. The first fill defined the index date/drug. Patients
were required to have a T2DM diagnosis (ICD-9-CM 250.x[0,2]) and >=12 months of
continuous enrollment pre- and post-index (follow-up). Main outcome measures were
adherence (proportion of days covered, PDC; medication possession ratio, MPR) and
persistence on index therapy. PDC or MPR >=0.80 was considered adherent. Patients
were considered persistent until evidence of discontinuation (gap >=90 days
between two subsequent index therapy prescriptions). Kaplan-Meier (KM) analysis
assessed time to discontinuation, while a Cox proportional hazards model (PHM)
evaluated risk of discontinuation. Logistic regression models evaluated the
likelihood of non-adherence. RESULTS: The final sample consisted of 23,702
patients (6,546 CANA, 3,087 DAPA, 6,273 GLP-1s, and 7,796 DPP-4s; 56% male, and
mean [SD] age = 55 [9.1] years). Mean PDC ranged from 0.56 (GLP-1), to 0.71
(CANA), with 33-56% adherent, respectively; MPR results were similar. Fifty-two
per cent (GLP-1) to 68% (CANA) were persistent over the follow-up. CANA patients
had the longest time to discontinuation. In regression analyses, compared to CANA
100 mg, DAPA, DPP-4, and GLP-1 patients had a significantly higher likelihood of
non-adherence and a significantly higher risk of discontinuation. CANA 300 mg
patients had a significantly lower likelihood of non-adherence and a
significantly lower risk of discontinuation compared to CANA 100 mg. CONCLUSIONS:
Adherence and persistence were significantly better with CANA (100 mg and 300 mg)
compared to DAPA, GLP-1s, and DPP-4s in the RW setting.
PMID- 28418263
TI - Systematic bias in predictions of new drugs' budget impact: analysis of a sample
of recent US drug launches.
AB - OBJECTIVE: Expectations about the budget impact of new drug launches may affect
payer behavior and ultimately consumer costs. Therefore, we evaluated the
accuracy of pre-launch US budget impact estimates for a sample of new drugs.
METHODS: We searched for publicly available budget impact estimates made pre
launch for drugs approved in the US from 1 September 2010 to 1 September 2015 and
compared them to actual sales. Accuracy was calculated as the ratio of pre-launch
estimate to actual sales. Quantitative analyses, including multivariate
regressions, were used to identify factors associated with accuracy. RESULTS: We
identified 25 budget impact estimates: 23 for one of 14 individual drugs and 2
for the category of PCSK9 inhibitors. The ratios of predicted to actual budget
impact ranged from 0.2 (estimate was 20% of sales) for secukinumab to 37.5
(estimate was 37.5 * sales) for PCSK9 inhibitors. Mean ratio was 5.5. In
multivariate analyses, larger eligible population, more recent estimate year
(e.g. 2015 vs. 2012), and being first in class, were associated with
statistically significant, greater overestimation of budget impact. CONCLUSIONS:
For every $5.5 of predicted cost, there was $1 of actual cost to the healthcare
system. This study, although based on a small, non-random sample, suggests
possible cognitive bias on the part of the estimators. Overestimating budget
impact may lead to early access restrictions, higher copays, and other changes
that ultimately impact patients. Analysts and non-profits should be attuned to
likely sources of error in order to improve their predictions.
PMID- 28418264
TI - Emission Characteristics of Laser-Induced Plasma Using Collinear Long and Short
Dual-Pulse Laser-Induced Breakdown Spectroscopy (LIBS).
AB - Collinear long and short dual-pulse laser-induced breakdown spectroscopy (DP
LIBS) was employed to clarify the emission characteristics from laser-induced
plasma. The plasma was sustained and became stable by the long pulse-width laser
with the pulse width of 60 MUs under free running (FR) conditions as an external
energy source. Comparing the measurement results of stainless steel in air using
single-pulse LIBS (SP-LIBS) and DP-LIBS, the emission intensity was markedly
enhanced using DP-LIBS. The temperature of plasma induced by DP-LIBS was
maintained at a higher temperature under different gate delay time and short
pulse-width laser power conditions compared with those measured using short SP
LIBS. Moreover, the variation rates of plasma temperatures measured using DP-LIBS
were also lower. The superior detection ability was verified by the measurement
of aluminum sample in water. The spectra were clearly detected using DP-LIBS,
whereas it cannot be identified using SP-LIBS of short and long pulse widths. The
effects of gate delay time and short pulse-width laser power were also discussed.
These results demonstrate the feasibility and enhanced detection ability of the
proposed collinear long and short DP-LIBS method.
PMID- 28418265
TI - Global health resource utilization associated with pacemaker complications.
AB - AIM: To estimate health resource utilization (HRU) associated with the management
of pacemaker complications in various healthcare systems. METHODS:
Electrophysiologists (EPs) from four geographical regions (Western Europe,
Australia, Japan, and North America) were invited to participate. Survey
questions focused on HRU in the management of three chronic pacemaker
complications (i.e. pacemaker infections requiring extraction, lead
fractures/insulation breaches requiring replacement, and upper extremity deep
venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys
(iterative rounds). Mean, median values, and interquartile ranges were calculated
and used to establish consensus. RESULTS: Overall, 32 and 29 panelists
participated in the first and second rounds of the Delphi panel, respectively.
Consensus was reached on treatment and HRU associated with a typical pacemaker
implantation and complications. HRU was similar across regions, except for Japan,
where panelists reported the longest duration of hospital stay in all scenarios.
Infections were the most resource-intensive complications and were characterized
by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket
and lead infections respectively; laboratory and diagnostic tests, and system
extraction and replacement procedures. DVT, on the other hand, was the least
resource intensive complication. LIMITATIONS: The results of the panel represent
the views of the respondents who participated and may not be generalizable
outside of this panel. The surveys were limited in scope and, therefore, did not
include questions on management of acute complications (e.g. hematoma,
pneumothorax). CONCLUSIONS: The Delphi technique provided a reliable and
efficient approach to estimating resource utilization associated with chronic
pacemaker complications. Estimates from the Delphi panel can be used to generate
costs of pacemaker complications in various regions.
PMID- 28418269
TI - Is a hollow centralizer necessary when using a polished, tapered, cemented
femoral stem?
AB - Background and purpose - A tapered, polished and collarless stem is normally
equipped with a hollow centralizer to prevent the stem from becoming end-bearing
in the cement as the stem subsides. In a randomized clinical trial, we evaluated
such a stem (MS-30), which was initially introduced with a solid centralizer but
was later recommended to be fitted with a hollow centralizer. We hypothesized
that while the stem would sink more, it would become rotationally stable and have
less retroversion with a hollow centralizer than with a solid centralizer.
Patients and methods - We randomized 60 patients with primary hip arthritis to
receive either a hollow centralizer or a solid centralizer with the stem. The
effect was evaluated over a 10-year follow-up period with repeated RSA
examinations, conventional radiographs, and clinical follow-ups using the WOMAC
and SF-12 questionnaires. Results - At 10-year follow-up, the group with hollow
centralizers had subsided more than the group with solid centralizers (1.99 mm
(hollow) as opposed to 0.57 mm (solid); p < 0.001). However, rotation was similar
at 10-year follow-up (mean retroversion 1.34 degrees (hollow) and 1.30 degrees
(solid)). Both groups showed excellent 10-year results, with similar clinical
outcome, and none of the stems were radiographically loose or had been revised.
Interpretation - As expected, there was more subsidence in the group with hollow
centralizers, and with similar magnitude to that reported in earlier RSA studies
on conceptually similar prostheses. Interestingly, there was no difference in the
rotational behavior of the prostheses. This stem type appears to have a design
that, regardless of the type of centralizer and the possibility of subsidence,
withstands the rotational forces it is subjected to very well. This study does
not support the need for a hollow centralizer for these types of stems.
PMID- 28418267
TI - BTKC481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia.
AB - Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in
chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse
has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can
cause relapse, but data regarding the prevalence and natural history of these
mutations are limited. Patients and Methods Patients accrued to four sequential
studies of ibrutinib were included in these analyses. Deep sequencing for BTK and
PLCG2 was performed retrospectively on patients who experienced relapse and
prospectively on a screening population. Results With a median follow-up time of
3.4 years, the estimated cumulative incidence of progression at 4 years is 19%
(95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1),
and age less than 65 years were risk factors for progression. Among patients who
experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95%
CI, 71% to 94%), and these mutations were detected an estimated median of 9.3
months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients
examined prospectively, eight patients have experienced relapse, and all of these
patients had acquired resistance mutations before relapse. A resistance mutation
was detected in an additional eight patients who have not yet met criteria for
clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after
ibrutinib is an issue of increasing clinical significance. We show that mutations
in BTK and PLCG2 appear early and have the potential to be used as a biomarker
for future relapse, suggesting an opportunity for intervention.
PMID- 28418268
TI - The folding competence of HIV-1 Tat mediated by interaction with TAR RNA.
AB - The trans-activator Tat protein of HIV-1 belongs to the large family of
intrinsically disordered proteins (IDPs), and is known to recruit various host
proteins for the transactivation of viral RNA synthesis. Tat protein interacts
with the transactivator response RNA (TAR RNA), exhibiting RNA chaperone
activities for structural rearrangement of interacting RNAs. Here, considering
that Tat-TAR RNA interaction is mutually cooperative, we examined the potential
role of TAR RNA as Chaperna - RNA that provides chaperone function to proteins -
for the folding of HIV-1 Tat. Using EGFP fusion as an indirect indicator for
folding status, we monitored Tat-EGFP folding in HeLa cells via time-lapse
fluorescence microscopy. The live cell imaging showed that the rate and the
extent of folding of Tat-EGFP were stimulated by TAR RNA. The purified Tat-EGFP
was denatured and the fluorescence was monitored in vitro under renaturation
condition. The fluorescence was significantly increased by TAR RNA, and the
mutations in TAR RNA that affected the interaction with Tat protein failed to
promote Tat refolding. The results suggest that TAR RNA stabilizes Tat as
unfolded, but prevents it from misfolding, and maintaining its folding competence
for interaction with multiple host factors toward its transactivation. The
Chaperna function of virally encoded RNA in establishing proteome link at the
viral-host interface provides new insights to as yet largely unexplored RNA
mediated protein folding in normal and dysregulated cellular metabolism.
PMID- 28418270
TI - USMLE and Otolaryngology: Predicting Board Performance.
AB - Objective To ascertain what relationship exists between the United States Medical
Licensing Examination (USMLE) and the American Board of Otolaryngology Written
Qualifying Examination (WQE). Study Design Retrospective, longitudinal study.
Setting De-identified database. Subjects Residents entering otolaryngology-head
and neck surgery (OHNS) residency between 2007 and 2009 and taking the WQE for
the first time between 2012 and 2014. Methods Regression models were used to
determine if the USMLE score predicts passage of the WQE on the first attempt,
which step score was a better predictor, and whether an increase in the Step 2
score increased the chances of WQE passage. Results There were 611 Step 1 and 402
Step 2 scores. Mean (SD) Step 1 score was 238 (14.4), and the mean (SD) Step 2
score was 243 (16.8). The overall WQE first-time passage rate was 95.3%. Step 1
score was a better predictor than Step 2 for successful passage of the WQE on the
first attempt ( P = .0026). An increase in the Step 2 score compared with the
Step 1 score did not predict an improved first-time passage rate on the WQE.
Conclusions There is an association between USMLE scores and successful first
time passage of the WQE, with Step 1 being a stronger predictor than Step 2.
Residents with USMLE scores lower than the average successful OHNS applicant
still have a high chance of passing the WQE. USMLE scores alone are of limited
usefulness in identifying those applicants at risk of failing the WQE on the
first attempt.
PMID- 28418271
TI - Use of a Novel Airway Kit and Simulation in Resident Training on Emergent
Pediatric Airways.
AB - Objective Development of a novel pediatric airway kit and implementation with
simulation to improve resident response to emergencies with the goal of improving
patient safety. Methods Prospective study with 9 otolaryngology residents
(postgraduate years 1-5) from our tertiary care institution. Nine simulated
pediatric emergency airway drills were carried out with the existing system and a
novel portable airway kit. Response times and time to successful airway control
were noted with both the extant airway system and the new handheld kit. Results
were analyzed to ensure parametric data and compared with t tests. A Bonferroni
adjustment indicated that an alpha of 0.025 was needed for significance. Results
Use of the airway kit significantly reduced the mean time of resident arrival by
47% ( P = .013) and mean time of successful intubation by 50% ( P = .007). Survey
data indicated 100% improved resident comfort with emergent airway scenarios with
use of the kit. Discussion Times to response and meaningful intervention were
significantly reduced with implementation of the handheld airway kit. Use of
simulation training to implement the new kit improved residents' comfort and
airway skills. This study describes an affordable novel mobile airway kit and
demonstrates its ability to improve response times. Implications for Practice The
low cost of this airway kit makes it a tenable option even for smaller hospitals.
Simulation provides a safe and effective way to familiarize oneself with novel
equipment, and, when possible, realistic emergent airway simulations should be
used to improve provider performance.
PMID- 28418272
TI - Incubation Temperature Alters Temperature-Dependent Oxygen Consumption in
Northern Bobwhite Quail Hatchlings (Colinus virginianus).
AB - This study investigated the effect of mismatching incubation and posthatch
temperatures in northern bobwhite quail hatchlings. Quail embryos were incubated
at 35.5 degrees or 37.5 degrees C. Metabolic rates were then measured in
hatchlings acclimated to either the same or the opposite temperature treatment.
While hatchlings expressed higher oxygen consumption when posthatch temperature
did not match incubation temperature, the effect of mismatching temperatures was
significant only when posthatch temperature was higher than incubation
temperature. Our data suggest that bobwhite quail hatchlings may express
increased metabolism due to mismatches between incubation and posthatch
temperatures. More specifically, the nature or direction of the mismatch can
determine the magnitude of the metabolic effect. These findings highlight the
importance of considering the context of specific conditions experienced
throughout ontogeny when observing phenotypic outcomes.
PMID- 28418273
TI - Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia:
A Preliminary Study.
AB - To evaluate the effectiveness of thalidomide for epistaxis in hereditary
hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were
treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to
100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the
treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after
starting thalidomide. The mean ESS before treatment, at the end of treatment, and
3 months after stopping treatment was 5.03 +/- 2.05, 0.90 +/- 0.84 ( P = .003),
and 1.98 +/- 1.33 ( P = .006), respectively. Four patients reported mild to
moderate side effects, including drowsiness, dizziness, constipation, nausea, and
peripheral neuropathy. Two patients stopped the treatment because of adverse
effects. Those results showed that thalidomide may be a treatment choice for
recurrent epistaxis in HHT patients, although the side effects should be
considered. Further study should focus on guidelines for dosing and course and
investigate how to reduce the adverse effects.
PMID- 28418275
TI - Factors Influencing Cochlear Patency after Translabyrinthine Surgery.
AB - Objective To determine predictive factors for cochlear obliteration after
translabyrinthine surgery for vestibular schwannoma. Study Design Case series
with chart review. Setting Neurotology referral center. Subjects and Methods In
total, 345 charts were reviewed, resulting in 103 patients who underwent
translabyrinthine surgery between January 2010 and July 2015 and had
postoperative magnetic resonance imaging (MRI) for review. Surveillance MRI
performed after translabyrinthine resection of vestibular schwannomas was
reviewed. Heavily T2-weighted MRI obtained an average of 21.8 months after
surgery was reviewed to assess cochlear patency. Tumor size, preoperative
audiograms, and MRI cochlear fluid-attenuated inversion recovery (FLAIR)
intensity were compared between patients with retained cochlear patency and those
without. Results Fifty-four percent of patients retained cochlear patency after
translabyrinthine surgery. Tumor size did not differ statistically between the 2
groups. There was no statistically significant difference in speech reception
thresholds, pure-tone average, or word recognition scores between patent and
nonpatent groups. Preoperative MRI FLAIR intensity did not differ between groups.
Conclusions More than half of patients retain cochlear patency after
translabyrinthine vestibular schwannoma surgery. Cochlear patency is required for
cochlear implant in patients with unilateral deafness. Preoperative tumor size,
hearing performance, and intensity on MRI FLAIR do not predict cochlear patency.
To prevent loss of opportunity for cochlear implantation, simultaneous
implantation and cochlear lumen keeper placement are options.
PMID- 28418274
TI - The Gulf Long-Term Follow-Up Study (GuLF STUDY): Biospecimen collection at
enrollment.
AB - The 2010 Deepwater Horizon (DWH) explosion in the Gulf of Mexico led to the
largest ever marine oil spill by volume. The GuLF STUDY is investigating possible
adverse human health effects associated with oil spill activities. One objective
of the study was to utilize biological specimens from study participants to
examine spill-related adverse health effects. This study describes the methods
for collecting, processing, shipping, and storing specimens during the enrollment
phase of the study. GuLF STUDY participants living in Gulf States (Alabama,
Florida, Louisiana, Mississippi, and eastern Texas) were eligible to complete a
home visit at enrollment, one to three years after the DWH explosion. During this
visit, blood, urine, toenail and hair clippings, and house dust samples were
collected. Specimens were shipped overnight to a central processing laboratory in
containers with cold and ambient temperature compartments. Most blood and urine
specimens were then aliquoted and stored in liquid nitrogen vapor or at -80
degrees C, with some samples stored at -20 degrees C. A total of 11,193
participants completed a home visit, and over 99% provided at least one
biospecimen. Most participants provided blood (93%), urine (99%), and toenail
clippings (89%), and 40% provided hair. Nearly all participants (95%) provided
house-dust samples. Most samples were received by the laboratory one (58%) or two
(25%) days after collection. These biospecimens enable investigation of a range
of biomarkers of spill-related adverse health effects, and possibly some
biomarkers of spill-related exposures. The biospecimen collection, handling, and
storage protocols were designed to maximize current and future scientific value
within logistical and budgetary constraints and might serve as a template for
future studies conducted in similar time-critical and geographically dispersed
settings.
PMID- 28418276
TI - Thrombin-antithrombin III complex tests.
AB - PURPOSE: Patients with fractures of the pelvis and/or lower extremities are at a
high risk of developing postoperative venous thromboembolism (VTE). The purpose
of this study was to determine whether the thrombin-antithrombin III complex
(TAT) tests could be used for postoperative screening of VTE in patients with
lower limb or pelvic fractures. METHODS: We enrolled 133 patients who underwent
surgical treatment for fracture of the pelvis or lower extremities. TAT and D
dimer levels were compared in patients with and without VTE. Receiver operating
characteristic (ROC) curve analysis was done and the appropriate TAT and D-dimer
cutoff levels were determined for VTE screening. RESULTS: VTE was diagnosed in 41
patients (30.8%). Patients with VTE had significantly higher levels of TAT and D
dimer on postoperative days 1, 3, and 7 than those without VTE, respectively. ROC
curve analysis suggested that TAT test at postoperative day 7 had the highest
accuracy for predicting postoperative VTE. With the optimal cutoff TAT level of
3.0 ng/mL, sensitivity and specificity were 93.3% and 70.1%, respectively. With
the optimal cutoff D-dimer level of 7.4 ug/mL, sensitivity and specificity were
93.3% and 57.0%, respectively. CONCLUSION: TAT levels measured at postoperative
day 7 could be the most useful parameter for screening postoperative VTE. TAT can
be used as a screening tool for screening postoperative VTE in patients with
lower limb and pelvic fractures.
PMID- 28418277
TI - Geographical variation in the skeletal morphology of red jungle fowl.
AB - 1. The skulls and postcranial skeletons of the red jungle fowl (Gallus gallus)
were compared osteometrically between the populations from North and South
Vietnam, North and Central Laos and Southeast Bangladesh. The populations include
the three subspecies of G. g. spadiceus, G. g. gallus and G. g. murghi and were
sampled to reveal the geographical morphological variations among populations in
G. gallus. 2. The morphometric characteristics of subspecies murghi could be
clearly distinguished from those of the other subspecies using a canonical
discriminant analysis. However, the size and shape of the skull of the gallus
population from South Vietnam were not statistically different from that of the
subspecies spadiceus from North Laos. The canonical discriminant scores also
clearly indicated that there were morphological similarities in the skulls of the
populations from North Laos and South Vietnam. 3. From the results, therefore, it
is concluded that red jungle fowls do not exhibit high levels of osteometric
variation between geographical localities at least within the Indochinese
Peninsula. 4. This contrasts with previous studies which have described these
subspecies as having various external morphological differences and have argued
that zoogeographical barriers exist between the north and south areas of the
Indochinese Peninsula.
PMID- 28418278
TI - The Effect of Surgical Insertion and Proinflammatory Cytokines on Osteochondral
Allograft Survival and Metabolism.
AB - Objective To investigate the responses of refrigerated osteochondral allograft
cartilage (OCA) and fresh cartilage (FC), including cell survival and metabolism,
to surgical impaction and proinflammatory cytokines. Design Osteochondral plugs
(8 mm diameter) were harvested from prolonged-refrigerated (14-28 days) and fresh
(<=24 hours postmortem) human femoral hemicondyles and subjected to a 0.2 N s
pneumatic impaction impulse. Cartilage explants were removed from subchondral
bone and randomized to 1 of 6 treatment groups: (1) Unimpacted control (UIC), (2)
Impacted control (IC), (3) Impacted + interleukin (IL)-1beta (0.1 ng/mL), (4)
Impacted + IL-1beta (0.1 ng/mL) + IL-6, (5) Impacted + IL-1beta (10 ng/mL), and
(6) Impacted + IL-1beta (10 ng/mL) + IL-6. Samples were measured for cell
viability, histology, and proteoglycan (PG) content at days 0, 2, 7, and 14 of
culture. Results In UIC, cell viability was indistinguishable between OCA and FC
and remained constant. Impaction alone decreased cell viability by 30% ( P <
0.01) in the OCA superficial layer and by 26% ( P < 0.01) in the entire tissue,
but did not affect viability in FC. Cytokine addition did not further influence
cell viability. Impaction alone did not affect PG synthesis. Addition of
cytokines to impacted tissue decreased PG synthesis by ~3-fold in both tissue
types in comparison with corresponding impacted controls ( P < 0.01). Throughout
2-week culture, PG release remained stable in all FC groups, but peaked at day 14
in OCA cartilage subjected to cytokines. Conclusions Mechanical impaction,
mimicking surgical insertion, has a more profound effect on cell viability in OCA
than in FC. Addition of proinflammatory cytokines further decreases OCA tissue
metabolism and integrity.
PMID- 28418279
TI - Intersectional stigma among midlife and older Black women living with HIV.
AB - HIV-related stigma is a barrier to the prevention and treatment of HIV. For
midlife and older Black women, the nature and intensity of HIV-related stigma may
be compounded by their multiple marginalised social status based on gender, race,
and age. We examined the perceptions and experiences of HIV-related stigma among
midlife and older Black women living in Prince George's County, Maryland, USA.
Between 2014 and 2015, we conducted semi-structured interviews with a sample of
35 midlife and older Black women living with HIV. Using a modified grounded
theory approach, we explored emergent themes related to the manifestation and
experience of intersectional stigma and changes in stigma experience over time.
Our findings suggest that intersectional stigma is a central feature in midlife
and older Black women's lives, with women reporting experiences of intersectional
stigma at the interpersonal/familial, community, and institutional/structural
levels. Although women acknowledged gradual acceptance of their HIV-positive
status over time, they continued to experience negative responses related to
gender, race, age, and disease. Our findings indicate that a more robust
understanding of the impact of HIV-related stigma requires work to consider the
complex manifestations of intersectional stigma among an increasingly aging
population of Black women in the USA.
PMID- 28418280
TI - Twenty-First Century Pathologists' Advocacy.
AB - Pathologists' advocacy plays a central role in the establishment of continuously
improving patient care quality and patient safety, and in the maintenance and
progress of pathology as a profession. Pathology advocacy's primary goal is the
betterment of patient safety and quality medical care; however, payment is a
necessary and appropriate component to both, and has a central role in advocacy.
Now is the time to become involved in pathology advocacy; the Medicare Access and
Children's Health Insurance Program (CHIP) Reauthorization Act of 2015 (MACRA)
and the Protecting Access to Medicare Act of 2014 (PAMA) are 2 of the most
consequential pieces of legislation impacting the pathology and laboratory
industry in the last 20 years. Another current issue of far-reaching impact for
pathologists is balance billing, and yet many pathologists have little or no
understanding of balance billing. Pathologists at all stages of their careers,
and in every professional setting, need to participate. Academic pathologists
have a special obligation to, if not become directly involved in advocacy, at
least have a broad and current understanding of those issues, as well as the need
and responsibility of pathologists to actively engage in advocacy efforts to
address them, in order to teach residents the place of advocacy, and its value,
as an inseparable and indispensable component of their professional
responsibilities.
PMID- 28418281
TI - Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1
(PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.
AB - CONTEXT: - Immune checkpoint pathways, including programmed death receptor
1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important
in mediating self-tolerance and controlling self-damage, can sometimes be
manipulated by cancer cells to evade immune surveillance. Recent clinical trials
further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various
cancers and reveal a new era of cancer immunotherapy. OBJECTIVE: - To review the
mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD
1/PD-L1 as a predictive and/or prognostic marker in various cancers, and
strategies of measuring PD-L1 expression. DATA SOURCES: - Representative medical
literature regarding PD-L1 expression in various cancers, including the
preliminary results of the Blue Proposal, which compares different
immunohistochemical stains for PD-L1 reported in the recent American Association
of Cancer Research (AACR) Annual Meeting (April 16-20, 2016). CONCLUSION: -
Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment
modalities provides benefit for patients with advanced cancers. Because of the
complexity of cancer immunity, we still do not have a reliable biomarker to
predict the response of PD-1/PD-L1-targeted therapy. Future studies, including
methods beyond immunohistochemical stains, are needed to develop reliable
biomarker/biomarkers for pathology laboratories to aid in selecting patients who
will benefit most from PD-1/PD-L1-targeted therapy.
PMID- 28418283
TI - Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.
AB - CONTEXT: - Bilirubin has strong anti-inflammatory and antioxidative stress
action. Progression of inflammation involving arteries is a crucial activator in
pathogenesis of Takayasu arteritis (TA). OBJECTIVE: - To investigate the
relationship between serum bilirubin and TA. DESIGN: - Our study involved 115
consecutive TA patients. Patients with active-phase disease were followed and
received prednisone therapy. RESULTS: - Lower concentrations of serum bilirubin
were detected in TA patients compared with healthy subjects (0.6 +/- 0.31 versus
0.7 +/- 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA
patients were lower than those in inactive patients (0.5 +/- 0.20 versus 0.8 +/-
0.32 mg/dL, P < .001). In all patients with TA, serum bilirubin correlated
positively with total protein (r = 0.193, P = .04) and negatively with C-reactive
protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532,
P < .001, respectively). Multiple logistic regression analysis showed that each
decrease of 1 mg/dL in serum bilirubin was associated with a 1.10 times increase
in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856
0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation
rate (beta = -0.170, P < .001) in multiple linear regression analysis. The area
under the curve for serum bilirubin in predicting active TA patients was 0.802.
Serum bilirubin levels were found to be significantly increased after prednisone
treatment (0.5 +/- 0.20 versus 0.7 +/- 0.15 mg/dL, P = .002). CONCLUSIONS: -
Lower serum bilirubin levels are associated with TA, and serum bilirubin may be
influenced by prednisone therapy in active TA patients. Serum bilirubin levels in
TA patients correlate negatively with erythrocyte sedimentation rate.
PMID- 28418282
TI - Immunohistochemical Detection of Hairy Cell Leukemia in Paraffin Sections: The
Role of Pax5 and CD103 Double Staining to Improve Specificity and Sensitivity.
AB - CONTEXT: - In hematopathology practice, abnormal expression of CD103 on B cells
is detected by flow cytometry in hairy cell leukemia (HCL) and, in combination
with other phenotypic and morphologic findings, provides diagnostic specificity
and sensitivity. Immunostaining on paraffin sections makes it possible to perform
immunophenotyping in situ. However, normal bone marrow contains CD103-positive
cells, which are not B cells, making it difficult to be certain about low-level
involvement by HCL. OBJECTIVE: - To develop dual immunostaining for confirmation
that CD103 is expressed in B cells, which may be highly desirable in assessing
low-level involvement by HCL. DESIGN: - We developed a dual immunostaining
approach using a B-cell marker, Pax5, expressed in the nucleus, in combination
with a membrane marker, CD103. RESULTS: - We analyzed 6 HCLs, 7 marginal zone
lymphomas, 12 lymphoplasmacytic lymphomas, 7 follicular lymphomas, 5 chronic
lymphocytic leukemias, 5 mantle cell lymphomas, 1 multiple myeloma (lymphocytic
variant), and 3 bone marrows not involved by any B-cell neoplasm. Our dual
staining approach confirmed that only the neoplastic cells of HCL were positive
for both CD103 and Pax5. CONCLUSIONS: - This dual-staining method is particularly
helpful in cases with low-level involvement by HCL and can be used for
determining minimal residual disease after treatment.
PMID- 28418285
TI - A new predictive tool for postoperative radiotherapy in prostate cancer.
AB - The standard treatments of localized prostate cancer include surgical resection
and/or radiotherapy. Recently in 2016, Zhao et al. described a tool to predict
which patients will most likely gain from postoperative radiotherapy. Such a
method can personalize treatment plan by maximizing benefit but minimizing harm.
PMID- 28418286
TI - External application of NF-kappaB inhibitor DHMEQ suppresses development of
atopic dermatitis-like lesions induced with DNCB/OX in BALB/c mice.
AB - CONTEXT: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as
an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of
NF-kappaB and has been shown to possess promising potential as an anti
inflammatory and anti-tumor agent. OBJECTIVE: This study examines DHMEQ's effect
on therapeutic potential for atopic dermatitis (AD)-like lesions. MATERIALS AND
METHODS: AD lesions were chronically induced by the repetitive and alternative
application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in
BALB/c mice. The mice were then externally treated with DHMEQ ointment.
Macroscopic and microscopic changes of the skin lesions were observed and
recorded. RESULTS: DHMEQ inhibited ear swelling and relieved clinical symptoms of
the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination
illustrated that it significantly decreased DNCB/OX-induced epidermal thickness,
the infiltration of inflammatory cells, and the count of mast cell. The elevated
level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon gamma
(IFN-gamma), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also
suppressed by DHMEQ. DISCUSSION AND CONCLUSION: This study indicated that DHMEQ
would be useful for the treatment of AD.
PMID- 28418287
TI - Synergistic Effect of Ischemic Preconditioning and Antithrombin in Ischemia
Reperfusion Injury.
AB - OBJECTIVES: Our study aimed to determine whether antithrombin plays a synergistic
role in accentuating the effects of intestinal ischemic preconditioning.
MATERIALS AND METHODS: Fifty rats were randomly allocated to 5 groups (10
rats/group) as follows: sham treatment (group 1); ischemia-reperfusion (group 2);
ischemic preconditioning followed by ischemia-reperfusion (group 3); antithrombin
+ ischemia-reperfusion, similar to group 2 but including antithrombin
administration (group 4); and antithrombin + ischemic preconditioning, similar to
group 3 but including antithrombin administration (group 5). Blood samples and
liver specimens were obtained for measurement of cytokines, myeloperoxidase, and
malondialdehyde. Liver biopsies were examined by electron microscopy. RESULTS:
Intestinal ischemia-reperfusion induced a remote hepatic inflammatory response as
evidenced by the striking increase of proinflammatory cytokines, myeloperoxidase,
and malondialdehyde. Tumor necrosis factor-alpha levels in group 5 (12.48 +/- 0.7
pg/mL) were significantly lower than in group 3 (13.64 +/- 0.78 pg/mL; P = .014).
Mean interleukin 1beta was lower in group 5 (9.52 +/- 0.67pg/mL) than in group 3
(11.05 +/- 1.9 pg/mL; P > .99). Mean interleukin 6 was also significantly lower
in group 5 (17.13 +/- 0.54 pg/mL) than in group 3 (23.82 +/- 1 pg/mL; P <= .001).
Myeloperoxidase levels were significantly higher in group 3 (20.52 +/- 2.26 U/g)
than in group 5 (18.59 +/- 1.03 U/g; P = .025). However, malondialdehyde levels
did not significantly improve in group 5 (4.55 +/- 0.46 MUmol) versus group 3
(5.17 +/- 0.61 MUmol; P = .286). Tumor necrosis factor-alpha, interleukin 6, and
myeloperoxidase findings show that antithrombin administration further attenuated
the inflammatory response caused by ischemia-reperfusion, suggesting a
synergistic effect with ischemic preconditioning. These findings were confirmed
by electron microscopy. CONCLUSIONS: The addition of antithrombin to ischemic
preconditioning may act to attenuate or prevent damage from ischemia-reperfusion
injury by inhibiting the release of cytokines and neutrophil infiltration.
PMID- 28418289
TI - Volatile organic compounds produced by a soil-isolate, Bacillus subtilis FA26
induce adverse ultra-structural changes to the cells of Clavibacter michiganensis
ssp. sepedonicus, the causal agent of bacterial ring rot of potato.
AB - Rhizobacterial volatile organic compounds (VOCs) play an important role in the
suppression of soil-borne phytopathogens. In this study, the VOCs produced by a
soil-isolate, Bacillus subtilis FA26, were evaluated in vitro for their
antibacterial activity against Clavibacter michiganensis ssp. sepedonicus (Cms),
the causal agent of bacterial ring rot of potato. The VOCs emitted by FA26
inhibited the growth of Cms significantly compared with the control. Scanning and
transmission electron microscopy analyses revealed distorted colony morphology
and a wide range of abnormalities in Cms cells exposed to the VOCs of FA26.
Varying the inoculation strategy and inoculum size showed that the production and
activity of the antibacterial VOCs of FA26 were dependent on the culture
conditions. Headspace solid-phase microextraction/gas chromatography-mass
spectrometry analyses revealed that FA26 produced 11 VOCs. Four VOCs
(benzaldehyde, nonanal, benzothiazole and acetophenone) were associated with the
antibacterial activity against Cms. The results suggested that the VOCs produced
by FA26 could control the causal agent of bacterial ring rot of potato. This
information will increase our understanding of the microbial interactions
mediated by VOCs in nature and aid the development of safer strategies for
controlling plant disease.
PMID- 28418288
TI - Immunopsychiatry: important facts.
AB - Accumulating evidence indicate a role for the immune system particularly
inflammation and autoimmunity in the aetiology of major psychiatric disorders
such as depression and schizophrenia. In this paper, we discuss some of the key
advances in immunopsychiatry in order to highlight to psychiatrists and other
health professionals how an increased understanding of this field might enhance
our knowledge of illness mechanism and approaches to treatment. We present a
brief overview of clinical research that link inflammation and autoimmunity with
depression and psychosis, including potential role of inflammation in treatment
response, current evidence for the effectiveness of immune-modulating treatment
for depression and psychosis, and possible role of inflammation in common
physical comorbidities for these disorders such as coronary heart disease and
diabetes mellitus. Gaining a better understanding of the role of immune system
could be paradigm changing for psychiatry. We need collaborations between
clinicians and scientists to deliver high-quality translational research in order
to fully realise the clinical potential of this exciting and rapidly expanding
field.
PMID- 28418290
TI - Invasive Nontuberculous Mycobacterial Infections among Cardiothoracic Surgical
Patients Exposed to Heater-Cooler Devices1.
AB - Invasive nontuberculous mycobacteria (NTM) infections may result from a
previously unrecognized source of transmission, heater-cooler devices (HCDs) used
during cardiac surgery. In July 2015, the Pennsylvania Department of Health
notified the Centers for Disease Control and Prevention (CDC) about a cluster of
NTM infections among cardiothoracic surgical patients at 1 hospital. We conducted
a case-control study to identify exposures causing infection, examining 11 case
patients and 48 control-patients. Eight (73%) case-patients had a clinical
specimen identified as Mycobacterium avium complex (MAC). HCD exposure was
associated with increased odds of invasive NTM infection; laboratory testing
identified patient isolates and HCD samples as closely related strains of M.
chimaera, a MAC species. This investigation confirmed a large US outbreak of
invasive MAC infections in a previously unaffected patient population and
suggested transmission occurred by aerosolization from HCDs. Recommendations have
been issued for enhanced surveillance to identify potential infections associated
with HCDs and measures to mitigate transmission risk.
PMID- 28418291
TI - Virulence Analysis of Bacillus cereus Isolated after Death of Preterm Neonates,
Nice, France, 2013.
AB - After the deaths of 2 preterm neonates with Bacillus cereus systemic infection in
the same intensive care unit, we investigated the pathogenic potential of this
bacterium. Genetic and virulence analysis indicated the neonates were infected
with 2 different strains with a virulence potential similar to environmental
strains, indicating likely patient immune response failure.
PMID- 28418292
TI - Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue
Virus Infection.
AB - Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect
Zika virus infection and confound serologic tests. Recent data demonstrate
neutralization of Zika virus by monoclonal antibodies or human serum collected
early after DENV infection. Whether this finding is true in late DENV
convalescence (>6 months after infection) is unknown. We studied late
convalescent serum samples from persons with prior DENV or Zika virus exposure.
Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was
not observed among primary DENV infections. We observed low-frequency (23%) Zika
virus cross-neutralization in repeat DENV infections. DENV-immune persons who had
Zika virus as a secondary infection had distinct populations of antibodies that
neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion
experiments. These data suggest that most DENV infections do not induce durable,
high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody
populations develop after Zika virus infection irrespective of prior DENV
immunity.
PMID- 28418293
TI - Insecticide-Treated Nets and Protection against Insecticide-Resistant Malaria
Vectors in Western Kenya.
AB - Insecticide resistance might reduce the efficacy of malaria vector control. In
2013 and 2014, malaria vectors from 50 villages, of varying pyrethroid
resistance, in western Kenya were assayed for resistance to deltamethrin. Long
lasting insecticide-treated nets (LLIN) were distributed to households at
universal coverage. Children were recruited into 2 cohorts, cleared of malaria
causing parasites, and tested every 2 weeks for reinfection. Infection incidence
rates for the 2 cohorts were 2.2 (95% CI 1.9-2.5) infections/person-year and 2.8
(95% CI 2.5-3.0) infections/person-year. LLIN users had lower infection rates
than non-LLIN users in both low-resistance (rate ratio 0.61, 95% CI 0.42-0.88)
and high-resistance (rate ratio 0.55, 95% CI 0.35-0.87) villages (p = 0.63). The
association between insecticide resistance and infection incidence was not
significant (p = 0.99). Although the incidence of infection was high among net
users, LLINs provided significant protection (p = 0.01) against infection with
malaria parasite regardless of vector insecticide resistance.
PMID- 28418294
TI - Exposure Risk for Infection and Lack of Human-to-Human Transmission of
Mycobacterium ulcerans Disease, Australia.
AB - We conducted epidemiologic and genetic analyses of family clusters of
Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found
that the incidence of M. ulcerans disease in family members was increased.
However, the risk for exposure appeared short-term and not related to human-human
transmission.
PMID- 28418295
TI - Phenotypic and Genotypic Shifts in Hepatitis B Virus in Treatment-Naive Patients,
Taiwan, 2008-2012.
AB - We examined the characteristic changes of hepatitis B virus (HBV) in antiviral
drug treatment-naive patients referred for pretreatment evaluation in Taiwan
during 2008-2012. Over time, we observed substantial decreases in the prevalence
of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation
and HBV-DNA levels in HBeAg-positive patients.
PMID- 28418296
TI - Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination
Policy, China.
AB - China's hepatitis B virus (HBV) prevention policy has been evaluated through
nationally representative serologic surveys conducted in 1992 and 2006. We report
results of a 2014 serologic survey and reanalysis of the 1992 and 2006 surveys in
the context of program policy. The 2014 survey used a 2-stage sample strategy in
which townships were selected from 160 longstanding, nationally representative,
county-level disease surveillance points, and persons 1-29 years of age were
invited to participate. The 2014 sample size was 31,713; the response rate was
83.3%. Compared with the 1992 pre-recombinant vaccine survey, HBV surface antigen
prevalence declined 46% by 2006 and by 52% by 2014. Among children <5 years of
age, the decline was 97%. China's HBV prevention program, targeted toward
interrupting perinatal transmission, has been highly successful and increasingly
effective. However, this progress must be sustained for decades to come, and
elimination of HBV transmission will require augmented strategies.
PMID- 28418297
TI - Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012.
AB - Survey results showed treponemal infection among pet macaques in Southeast Asia,
a region with a high prevalence of human yaws. This finding, along with studies
showing treponemal infection in nonhuman primates in Africa, should encourage a
One Health approach to yaws eradication and surveillance activities, possibly
including monitoring of nonhuman primates in yaws-endemic regions.
PMID- 28418298
TI - ESBL- and Carbapenemase-Producing Enterobacteriaceae in Patients with Bacteremia,
Yangon, Myanmar, 2014.
AB - Among 42 gram-negative bloodstream isolates from inpatients in 3 hospitals in
Yangon, Myanmar, admitted during July-December 2014, 16 (38%) were extended
spectrum beta-lactamase-producing Enterobacteriaceae and 6 (14%) produced
carbapenemase. The high prevalence of multidrug-resistant gram-negative bacteria
raises concerns about the empiric treatment of patients with sepsis in Yangon.
PMID- 28418299
TI - Control of Malaria Vector Mosquitoes by Insecticide-Treated Combinations of
Window Screens and Eave Baffles.
AB - We assessed window screens and eave baffles (WSEBs), which enable mosquitoes to
enter but not exit houses, as an alternative to indoor residual spraying (IRS)
for malaria vector control. WSEBs treated with water, the pyrethroid lambda
cyhalothrin, or the organophosphate pirimiphos-methyl, with and without a binding
agent for increasing insecticide persistence on netting, were compared with IRS
in experimental huts. Compared with IRS containing the same insecticide, WSEBs
killed similar proportions of Anopheles funestus mosquitoes that were resistant
to pyrethroids, carbamates and organochlorines and greater proportions of
pyrethroid-resistant, early exiting An. arabiensis mosquitoes. WSEBs with
pirimiphos-methyl killed greater proportions of both vectors than lambda
cyhalothrin or lambda-cyhalothrin plus pirimiphos-methyl and were equally
efficacious when combined with binding agent. WSEBs required far less insecticide
than IRS, and binding agents might enhance durability. WSEBs might enable
affordable deployment of insecticide combinations to mitigate against physiologic
insecticide resistance and improve control of behaviorally resistant, early
exiting vectors.
PMID- 28418300
TI - Population Responses during the Pandemic Phase of the Influenza A(H1N1)pdm09
Epidemic, Hong Kong, China.
AB - During August 2009-July 2010, we conducted 7 longitudinal telephone surveys among
503 adults in Hong Kong, China, to explore changes in their behavioral and
psychological responses to the influenza A(H1N1)pdm09 virus epidemic. Trends were
examined using generalized estimating equations models. Findings showed that
responses varied with the course of the pandemic.
PMID- 28418301
TI - Severe MRSA Enterocolitis Caused by a Strain Harboring Enterotoxins D, G, and I.
AB - We describe a case of methicillin-resistant Staphylococcus aureus (MRSA)
enterocolitis in a healthy adult with previous antibiotic exposure. Colonoscopy
revealed diffuse colitis and mild ileitis without ulceration. Stool cultures
demonstrated abundant growth of MRSA and absent normal flora. Oral vancomycin
treatment was effective and seems to be the consensus choice for therapy.
PMID- 28418302
TI - Anthrax Cases Associated with Animal-Hair Shaving Brushes.
AB - During the First World War, anthrax cases in the United States and England
increased greatly and seemed to be associated with use of new shaving brushes.
Further investigation revealed that the source material and origin of shaving
brushes had changed during the war. Cheap brushes of imported horsehair were
being made to look like the preferred badger-hair brushes. Unfortunately, some of
these brushes were not effectively disinfected and brought with them a nasty
stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data,
and case reports indicated that these cases originated from the use of
ineffectively disinfected animal-hair shaving brushes. This historical
information is relevant to current public health practice because renewed
interest in vintage and animal-hair shaving brushes has been seen in popular
culture. This information should help healthcare providers and public health
officials answer questions on this topic.
PMID- 28418303
TI - Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria
gonorrhoeae, Hawaii, USA.
AB - During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were
resistant to azithromycin; 5 had decreased in vitro susceptibility to
ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when
compared with local contemporary strains. Continued evolution and widespread
transmission of these strains might challenge the effectiveness of current
therapeutic options.
PMID- 28418304
TI - Meningococci of Serogroup X Clonal Complex 181 in Refugee Camps, Italy.
AB - Four cases of infection with serogroup X meningococci (MenX) (1 in 2015 and 3 in
2016) occurred in migrants living in refugee camps or reception centers in Italy.
All MenX isolates were identified as clonal complex 181. Our report suggests that
serogroup X represents an emerging health threat for persons arriving from
African countries.
PMID- 28418305
TI - Clinical Manifestations of Punta Toro Virus Species Complex Infections, Panama,
2009.
AB - An investigation in Panama found that Punta Toro virus species complex (PTVs) may
contribute to febrile illnesses with symptoms mirroring those of dengue fever.
However, further studies are needed to determine if PTV infection causes only a
mild disease or if it can have more serious manifestations in some patients.
PMID- 28418306
TI - Management of Bartonella Prosthetic Valve Endocarditis without Cardiac Surgery.
AB - Two cases of Bartonella prosthetic valve endocarditis were cured when treated for
2 weeks with gentamicin and 3 months with doxycycline. Clinical cure correlated
with decreased Bartonella antibody titers. This report suggests a strategy to
monitor, treat, and cure Bartonella prosthetic valve endocarditis.
PMID- 28418307
TI - Serogroup B Meningococcal Disease Vaccine Recommendations at a University, New
Jersey, USA, 2016.
AB - In response to a university-based serogroup B meningococcal disease outbreak, the
serogroup B meningococcal vaccine Trumenba was recommended for students, a rare
instance in which a specific vaccine brand was recommended. This outbreak
highlights the challenges of using molecular and immunologic data to inform real
time response.
PMID- 28418308
TI - Chromosomal 16S Ribosomal RNA Methyltransferase RmtE1 in Escherichia coli
Sequence Type 448.
AB - We identified rmtE1, an uncommon 16S ribosomal methyltransferase gene, in an
aminoglycoside- and cephalosporin-resistant Escherichia coli sequence type 448
clinical strain co-harboring blaCMY-2. Long-read sequencing revealed insertion of
a 101,257-bp fragment carrying both resistance genes to the chromosome. Our
findings underscore E. coli sequence type 448 as a potential high-risk multidrug
resistant clone.
PMID- 28418309
TI - Translation of Real-Time Infectious Disease Modeling into Routine Public Health
Practice.
AB - Infectious disease dynamic modeling can support outbreak emergency responses. We
conducted a workshop to canvas the needs of stakeholders in Australia for
practical, real-time modeling tools for infectious disease emergencies. The
workshop was attended by 29 participants who represented government, defense,
general practice, and academia stakeholders. We found that modeling is underused
in Australia and its potential is poorly understood by practitioners involved in
epidemic responses. The development of better modeling tools is desired. Ideal
modeling tools for operational use would be easy to use, clearly indicate
underlying parameterization and assumptions, and assist with policy and decision
making.
PMID- 28418311
TI - Reemergence of African Swine Fever in Zimbabwe, 2015.
AB - Zimbabwe is the only country in southern Africa with no reported African swine
fever (ASF) outbreaks during 1993-2014. However, the 2015 discovery of genotype
II ASF virus in Zimbabwe indicates the reemergence of ASF in this country and
suggests that this viral genotype may be spreading through eastern and southern
Africa.
PMID- 28418310
TI - Diagnosis and Management of Borrelia turicatae Infection in Febrile Soldier,
Texas, USA.
AB - In August 2015, a soldier returned from field exercises in Texas, USA, with
nonspecific febrile illness. Culture and sequencing of spirochetes from
peripheral blood diagnosed Borrelia turicatae infection. The patient recovered
after receiving doxycycline. No illness occurred in asymptomatic soldiers
potentially exposed to the vector tick and prophylactically given treatment.
PMID- 28418312
TI - Exposure Characteristics of Hantavirus Pulmonary Syndrome Patients, United
States, 1993-2015.
AB - Those at highest risk are persons in occupations with potential for rodent
exposure and American Indian women 40--64 years of age.
PMID- 28418313
TI - mcr-1 Colistin Resistance in ESBL-Producing Klebsiella pneumoniae, France.
AB - We report intestinal carriage of an extended-spectrum beta-lactamase-producing
Klebsiella pneumoniae strain with high-level resistance to colistin (MIC 24 mg/L)
in a patient in France who had been hospitalized for fungal meningitis. The
strain had the mcr-1 plasmid gene and an inactivated mgrB gene, which are
associated with colistin resistance.
PMID- 28418314
TI - Population Genomics of Legionella longbeachae and Hidden Complexities of
Infection Source Attribution.
AB - Legionella longbeachae is the primary cause of legionellosis in Australasia and
Southeast Asia and an emerging pathogen in Europe and the United States; however,
our understanding of the population diversity of L. longbeachae from patient and
environmental sources is limited. We analyzed the genomes of 64 L. longbeachae
isolates, of which 29 were from a cluster of legionellosis cases linked to
commercial growing media in Scotland in 2013 and 35 were non-outbreak-associated
isolates from Scotland and other countries. We identified extensive genetic
diversity across the L. longbeachae species, associated with intraspecies and
interspecies gene flow, and a wide geographic distribution of closely related
genotypes. Of note, we observed a highly diverse pool of L. longbeachae genotypes
within compost samples that precluded the genetic establishment of an infection
source. These data represent a view of the genomic diversity of L. longbeachae
that will inform strategies for investigating future outbreaks.
PMID- 28418315
TI - Regional Transmission of Salmonella Paratyphi A, China, 1998-2012.
AB - To explore transmission patterns and genetic relationships of Salmonella enterica
serovar Paratyphi A in China, we conducted a genome-wide single-nucleotide
polymorphism analysis on the strains in the 4 provinces in which incidence was
highest during 1998-2012. Markedly phylogeographic clustering suggested regional
virus circulation after introduction from areas in southeastern China.
PMID- 28418316
TI - Amoxicillin and Ceftriaxone as Treatment Alternatives to Penicillin for Maternal
Syphilis.
AB - There is no proven alternative to penicillin for treatment of maternal syphilis.
We report 2 case-patients with maternal syphilis who were successfully treated
without penicillin. We used amoxicillin and probenecid for the first case-patient
and amoxicillin, probenecid, and ceftriaxone for the second case-patient.
PMID- 28418317
TI - No Such Thing as Chronic Q Fever.
AB - Modern diagnostic methods enable clinicians to look beyond a diagnosis of chronic
Q fever and discern whether patients instead have persistent focalized Coxiella
burnetii infection(s). Use of these methods and development of criteria to define
and treat such infections, especially cardiovascular infections, will improve the
prognosis for patients previously thought to have chronic Q fever.
PMID- 28418318
TI - Carbapenem-Resistant Enterobacter cloacae in Patients from the US Veterans Health
Administration, 2006-2015.
AB - We analyzed carbapenem-resistant Enterobacteriaceae (CRE) trends among patients
from the US Veterans Health Administration (VHA). After the emergence of CRE in
the eastern United States, resistance rates remained stable in Klebsiella
pneumoniae but increased in Enterobacter cloacae complex, suggesting a "second
epidemic". VHA offers a vantage point for monitoring nationwide CRE trends.
PMID- 28418319
TI - Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium.
AB - Escalating resistance to azithromycin and moxifloxacin is being reported for
Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we
found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA
(5%). ParC S83 changes were associated with moxifloxacin failure. Combined
macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for
which recommended therapies would be ineffective.
PMID- 28418320
TI - Antimicrobial Drug Resistance among Refugees from Syria, Jordan.
PMID- 28418322
TI - Binaural Interference: Quo Vadis?
AB - The reality of the phenomenon of binaural interference with speech recognition
has been debated for two decades. Research has taken one of two avenues; group
studies or case reports. In group studies, a sample of the elderly population is
tested on speech recognition under three conditions; binaural, monaural right and
monaural left. The aim is to determine the percent of the sample in which the
expected outcome (binaural score-better-than-either-monaural score) is reversed
(i.e., one of the monaural scores is better than the binaural score). This
outcome has been commonly used to define binaural interference. The object of
group studies is to answer the "how many" question, what is the prevalence of
binaural interference in the sample. In case reports the binaural interference
conclusion suggested by the speech recognition tests is not accepted until it has
been corroborated by other independent diagnostic audiological measures. The aim
is to attempt to determine the basis for the findings, to answer the "why"
question. This article is at once tutorial, editorial and a case report. We argue
that it is time to accept the reality of the phenomenon of binaural interference,
to eschew group statistical approaches in search of an answer to the "how many"
question, and to focus on individual case reports in search of an answer to the
"why" question.
PMID- 28418321
TI - S100A10 identified in a genome-wide gene * cannabis dependence interaction
analysis of risky sexual behaviours.
AB - BACKGROUND: We conducted a genome-wide gene * environment interaction analysis to
identify genetic variants that interact with cannabis dependence (CaD) in
influencing risky sexual behaviours (RSB). METHODS: Our sample included cannabis
exposed and sexually experienced African-American and European-American
participants. A DSM-IV CaD diagnosis and RSB were evaluated using the Semi
Structured Assessment for Drug Dependence and Alcoholism. We analyzed RSBs as a
score that takes into account experiences of unprotected sex and multiple sexual
partners. RESULTS: A total of 3350 people participated in our study; 43% had a
CaD diagnosis, 56% were African-American and 33% were women. We identified a
genome-wide significant locus in African-American participants (S100A10
rs72993629, p = 2.73 * 10-8) and a potential transpopulation signal in women
(CLTC rs12944716, p = 5.27 * 10-8). A resting-state fMRI follow-up analysis of
S100A10 rs72993629 conducted in an independent cohort showed 2 significant
associations: reduced power of the left paracentral lobule in amplitude of low
frequency fluctuations (ALFF) analysis (p = 7.8 * 10-3) and reduced power of the
right pallidum in fractional ALFF analysis (p = 4.6 * 10-3). The activity of
these brain regions is known to be involved in sexual functions and behaviours.
The S100A10 result functionally recapitulated our S100B finding observed in our
previous genome-wide association study of CaD. The probability of identifying 2
S100 genes in 2 independent genome-wide investigations by chance is approximately
1 in 1.1 million. LIMITATIONS: We were not able to identify any African-American
cohort with appropriate sample size, and phenotypic assessment is available to
replicate our findings. CONCLUSION: The S100A10 and S100B genes, which are
located on different chromosomes, encode specialized calcium-binding proteins.
These data support a role for calcium homeostasis in individuals with CaD and its
induced behaviours.
PMID- 28418323
TI - The Personality Profile of Tinnitus Sufferers and a Nontinnitus Control Group.
AB - BACKGROUND: Chronic tinnitus (phantom perception of sound) significantly disrupts
quality of life in 15-20% of those who experience it. Understanding how certain
personality traits impact tinnitus perception and distress can be beneficial for
the development of interventions to improve the lives of tinnitus sufferers.
PURPOSE: Four key self-reported personality traits (social closeness, stress
reaction, alienation, and self-control) were identified from previous research as
being associated with tinnitus. These were compared between tinnitus and age-,
gender-, and hearing level-matched nontinnitus controls to see whether underlying
profile differences exist, and if personality traits levels correlate with
various tinnitus characteristics assessed in typical clinical questionnaires.
RESEARCH DESIGN: A Web-based personality survey was administered comprising of
self-control, stress reaction, alienation, and social closeness subscale
questions of the Multidimensional Personality Questionnaire, the Hearing Handicap
Inventory-Screening Version, TFI, and the Tinnitus Case History Questionnaire.
STUDY SAMPLE: A total of 154 participants with tinnitus (81 males, 73 females,
mean age = 62.6 yr) and 61 control (32 males, 29 females, mean age = 59.62 yr)
participants were recruited via e-mail invitations to a tinnitus research clinic
database, poster, and social media Web site advertising. DATA COLLECTION AND
ANALYSIS: Statistical analysis was conducted using parametric statistics and IBM
SPSS(r) Version 22 software. RESULTS: Tinnitus sufferers displayed higher levels
of stress reaction, lower social closeness, lower self-control, and higher
alienation than the control group (p < 0.05). Alienation was related to tinnitus
pitch and self-reported hyperacusis measured using the Tinnitus Case History
Questionnaire (p < 0.05). Stress reaction correlated with self-reported
hyperacusis, whether tinnitus sufferers had sought other treatments, and whether
loud sounds make the tinnitus worse (p < 0.05). CONCLUSIONS: The four personality
traits examined in this study exhibited a consistent association with tinnitus
perception and distress, and differentiated tinnitus sufferers from nontinnitus
control. Some of the traits also correlated significantly with certain
characteristics measured in tinnitus history questionnaires. Personality traits
are described in relation to "maladaptive" residuals under the Adaptation Level
Theory model of tinnitus. The results of the study suggest that certain
personality traits correlate with the clinical presentation of tinnitus.
PMID- 28418324
TI - Prosody Perception and Production in Children with Hearing Loss and Age- and
Gender-Matched Controls.
AB - BACKGROUND: Auditory development in children with hearing loss, including the
perception of prosody, depends on having adequate input from cochlear implants
and/or hearing aids. Lack of adequate auditory stimulation can lead to delayed
speech and language development. Nevertheless, prosody perception and production
in people with hearing loss have received less attention than other aspects of
language. The perception of auditory information conveyed through prosody using
variations in the pitch, amplitude, and duration of speech is not usually
evaluated clinically. PURPOSE: This study (1) compared prosody perception and
production abilities in children with hearing loss and children with normal
hearing; and (2) investigated the effect of age, hearing level, and musicality on
prosody perception. RESEARCH DESIGN: Participants were 16 children with hearing
loss and 16 typically developing controls matched for age and gender. Fifteen of
the children with hearing loss were tested while using amplification (n = 9
hearing aids, n = 6 cochlear implants). Six receptive subtests of the Profiling
Elements of Prosody in Speech-Communication (PEPS-C), the Child Paralanguage
subtest of Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA 2), and Contour and
Interval subtests of the Montreal Battery of Evaluation of Amusia (MBEA) were
used. Audio recordings of the children's reading samples were rated using a
perceptual prosody rating scale by nine experienced listeners who were blinded to
the children's hearing status. STUDY SAMPLE: Thirty two children, 16 with hearing
loss (mean age = 8.71 yr) and 16 age- and gender-matched typically developing
children with normal hearing (mean age = 8.87 yr). DATA COLLECTION AND ANALYSIS:
Assessments were completed in one session lasting 1-2 hours in a quiet room. Test
items were presented using a laptop computer through loudspeaker at a comfortable
listening level. For children with hearing loss using hearing instruments, all
tests were completed with hearing devices set at their everyday listening
setting. RESULTS: All PEPS-C subtests and total scores were significantly lower
for children with hearing loss compared to controls (p < 0.05). The hearing loss
group performed more poorly than the control group in recognizing happy, sad, and
fearful emotions in the DANVA 2 subtest. Musicality (composite MBEA scores and
musical experience) was significantly correlated with prosody perception scores,
but this link was not evident in the regression analyses. Regression modeling
showed that age and hearing level (better ear pure-tone average) accounted for
55.4% and 56.7% of the variance in PEPS-C and DANVA 2 total scores, respectively.
There was greater variability for the ratings of pitch, pitch variation, and
overall impression of prosody in the hearing loss group compared to control
group. Prosody perception (PEPS-C and DANVA 2 total scores) and ratings of
prosody production were not correlated. CONCLUSIONS: Children with hearing loss
aged 7-12 yr had significant difficulties in understanding different aspects of
prosody and were rated as having more atypical prosody overall than controls.
These findings suggest that clinical assessment and speech-language therapy
services for children with hearing loss should be expanded to target prosodic
difficulties. Future studies should investigate whether musical training is
beneficial for improving receptive prosody skills.
PMID- 28418325
TI - Variation in Music Player Listening Level as a Function of Campus Location.
AB - BACKGROUND: There has been significant discussion in the literature regarding
music player use by adolescents and young adults, including whether device use is
driving an increase in hearing loss in these populations. While many studies
report relatively safe preferred listening levels, some studies with college
student participants have reported listening habits that may put individuals at
risk for noise-induced hearing loss (NIHL) if those listening habits continue
over the long term. PURPOSE: The goal of the current investigation was to extend
listening level data collection sites from urban city settings studied by others
to a more rural campus setting. RESEARCH DESIGN: This was a prospective study.
STUDY SAMPLE: Participants were 138 students on the University of Florida campus
(94 males, 44 females), 18 years or older (mean = 21 years; range: 18-33 years).
DATA COLLECTION AND ANALYSIS: In this investigation, the current output level
(listening level) was measured from personal listening devices used by students
as they passed by a recruiting table located in one of three areas of the
University of Florida campus. One location was in an open-air campus square; the
other two locations were outside the campus recreation building ("gym") and
outside the undergraduate library, with participants recruited as they exited the
gym or library buildings. After providing written informed consent, participants
completed a survey that included questions about demographics and typical
listening habits (hours per day, days per week). The output level on their device
was then measured using a "Jolene" mannequin. RESULTS: Average listening levels
for participants at the three locations were as follows: gym: 85.9 +/- 1.4 dBA;
campus square: 83.3 +/- 2.0 dBA; library: 76.9 +/- 1.3 dBA. After adjusting to
free-field equivalent level, average listening levels were gym: 79.7 +/- 1.4 dBA;
campus square: 76.9 +/- 2.1 dBA; library: 70.4 +/- 1.4 dBA. There were no
statistically significant differences between male and female listeners, and
there were no reliable differences as a function of race. After accounting for
daily and weekly use patterns, 5% were deemed at risk based on the criteria put
forward by the Occupational Safety and Health Administration, and 9% were deemed
at risk based on the guidance provided by the National Institute for Occupational
Safety and Health. CONCLUSIONS: Some 5-10% of the participants were deemed at
risk; this finding is consistent with other studies using similar methods. It is
possible that the same listeners would have selected different listening levels
in other noise backgrounds, however. This unknown variable makes it difficult to
estimate risk with a single listening level measurement.
PMID- 28418326
TI - Artifact in Pediatric Oculomotor Findings during Videonystagmography: A
Retrospective Analysis.
AB - BACKGROUND: Accurate measurement of oculomotor function using videonystagmography
(VNG) is imperative for diagnosis and management of patients with reported
dizziness. The oculomotor evaluation during VNG utilizes video-oculography
providing valuable information regarding the central structures and pathways that
control eye movements. Artifact may have an effect on the overall validity and
reliability of VNG oculomotor tracings and can result from patient and/or
recording errors. It is postulated that artifact could occur more frequently in
the pediatric population due to both patient and equipment factors. PURPOSE: The
purpose of this study was to systematically evaluate the occurrence and impact of
artifact on saccades, smooth pursuit, and optokinetic (OPK) testing in normal
pediatric and adult subjects using commercially available clinical VNG equipment
and standard clinical protocols for oculomotor testing. RESEARCH DESIGN: The
present study utilized a retrospective analysis of a repeated measures design.
STUDY SAMPLE: Oculomotor results from a total of 62 participants were analyzed.
Portions of these data have been presented in a previous research study. Group 1
consisted of twenty-nine 4- to 6-yr-olds with an average age of 4.86 (SD = 0.88)
yr. Group 2 consisted of thirty-three 22- to 44-yr-olds with an average age of
25.2 (SD = 5.34) yr. DATA COLLECTION AND ANALYSIS: Raw oculomotor recordings were
analyzed "offline" by a single masked, trained investigator. Each tracing was
evaluated for instances of artifact including eye blinks, eye closure, eyes
moving in opposite direction of the target, eye tracking software problems, and
overall poor morphology. The number of instances of artifact were noted and
recorded for each participant in both groups. Individual eye movements not
affected by artifact were included for final analysis. Artifact rejection
techniques were also compared. RESULTS: The results indicated increased artifact
for the pediatric group for saccade and smooth pursuit testing. Additionally, a
significant decrease in instances of artifact was noted with an increase in age
in months for both saccade and smooth pursuit findings. OPK results did not
indicate any significant difference in instances of artifact between the
pediatric and adult groups or any decrease in instances of artifact with
increasing age in the pediatric group. Artifact rejection technique did not have
a significant effect on oculomotor measures for either age group. CONCLUSIONS:
Pediatric patients exhibit increased instances of artifact during VNG oculomotor
testing, specifically during saccade and smooth pursuit testing, at least for the
4- to 6-yr-old population. A general age effect was also noted in this age group,
with decreased artifact noted with increasing age. Artifact rejection technique
was not a significant factor suggesting standard compared based strategies may be
sufficient for use in the pediatric population. Additional study into the effect
of artifact on oculomotor results for infants to age 3 yr and ages 7- to 18-yr
old, in the disordered population, and with additional equipment manufacturers is
needed to confirm these results and further describe the impact of artifact on
oculomotor findings in the pediatric population.
PMID- 28418327
TI - Auditory and Cognitive Factors Associated with Speech-in-Noise Complaints
following Mild Traumatic Brain Injury.
AB - BACKGROUND: Auditory complaints following mild traumatic brain injury (MTBI) are
common, but few studies have addressed the role of auditory temporal processing
in speech recognition complaints. PURPOSE: In this study, deficits understanding
speech in a background of speech noise following MTBI were evaluated with the
goal of comparing the relative contributions of auditory and nonauditory factors.
RESEARCH DESIGN: A matched-groups design was used in which a group of listeners
with a history of MTBI were compared to a group matched in age and pure-tone
thresholds, as well as a control group of young listeners with normal hearing
(YNH). STUDY SAMPLE: Of the 33 listeners who participated in the study, 13 were
included in the MTBI group (mean age = 46.7 yr), 11 in the Matched group (mean
age = 49 yr), and 9 in the YNH group (mean age = 20.8 yr). DATA COLLECTION AND
ANALYSIS: Speech-in-noise deficits were evaluated using subjective measures as
well as monaural word (Words-in-Noise test) and sentence (Quick Speech-in-Noise
test) tasks, and a binaural spatial release task. Performance on these measures
was compared to psychophysical tasks that evaluate monaural and binaural temporal
fine-structure tasks and spectral resolution. Cognitive measures of attention,
processing speed, and working memory were evaluated as possible causes of
differences between MTBI and Matched groups that might contribute to speech-in
noise perception deficits. RESULTS: A high proportion of listeners in the MTBI
group reported difficulty understanding speech in noise (84%) compared to the
Matched group (9.1%), and listeners who reported difficulty were more likely to
have abnormal results on objective measures of speech in noise. No significant
group differences were found between the MTBI and Matched listeners on any of the
measures reported, but the number of abnormal tests differed across groups.
Regression analysis revealed that a combination of auditory and auditory
processing factors contributed to monaural speech-in-noise scores, but the
benefit of spatial separation was related to a combination of working memory and
peripheral auditory factors across all listeners in the study. CONCLUSIONS: The
results of this study are consistent with previous findings that a subset of
listeners with MTBI has objective auditory deficits. Speech-in-noise performance
was related to a combination of auditory and nonauditory factors, confirming the
important role of audiology in MTBI rehabilitation. Further research is needed to
evaluate the prevalence and causal relationship of auditory deficits following
MTBI.
PMID- 28418328
TI - Internet-Based Intervention for Tinnitus: Outcome of a Single-Group Open Trial.
AB - BACKGROUND: Managing chronic tinnitus is challenging, and innovative ways to
address the resulting health-care burden are required. Internet-based cognitive
behavioral therapy (iCBT) for tinnitus shows promise as a cost-effective
treatment option. The feasibility and effectiveness of iCBT in the United Kingdom
are yet to be explored. Furthermore, it is not known if iCBT can be supported by
an audiologist rather than a psychologist. PURPOSE: This study aimed to determine
the feasibility of guided iCBT using audiological support on tinnitus distress
and tinnitus-related comorbidities. Furthermore, it aimed to establish the
feasibility of iCBT for tinnitus distress in the United Kingdom, by determining
recruitment, attrition, and compliance rates. Finally, it aimed to identify which
aspects of the protocol require refinement for subsequent clinical trials.
RESEARCH DESIGN: A single-group open trial design was implemented. This study
would serve as a prerequisite study, to identify barriers, before undertaking
effectiveness trials. STUDY SAMPLE: Participants consisted of 37 adults (18
males, 19 females), with an age range of between 50 and 59 yr. The mean
preintervention tinnitus severity rating was 56.15 (standard deviation = 18.35),
which is categorized as "severe tinnitus" as measured by the Tinnitus Functional
Index (TFI). Five participants withdrew during the study, and 29 of the remaining
participants completed the postintervention questionnaire. INTERVENTION: The
guided iCBT intervention ran over an eight-week period and consisted of 16
obligatory modules and five optional modules. The intervention was designed to be
interactive, interesting, and stimulating. A key element was the provision of
support from an audiologist throughout the program. DATA COLLECTION AND ANALYSIS:
Online questionnaires were used throughout the study. These were administered at
baseline and postintervention to determine attrition and compliance rates and to
facilitate sample size estimates for further clinical trials. Outcome measures
for tinnitus severity, hearing handicap, insomnia, cognitive functioning,
hyperacusis, anxiety, depression, and life satisfaction were used to investigate
the effects of iCBT with audiological support. In addition, a weekly
questionnaire was incorporated to monitor change in tinnitus distress while
undertaking the intervention. RESULTS: Feasibility was established using an
audiologist to support this guided iCBT intervention, as a significant change
postintervention was found for tinnitus severity, as measured by the TFI and the
Tinnitus Handicap Inventory, Screening version. The attrition rate was 22% and
compliance was variable. Although these results were based on a small sample,
they provide encouraging evidence for the feasibility of delivering iCBT
treatment for tinnitus symptoms with audiology support in the United Kingdom.
CONCLUSIONS: An Internet-based intervention of tinnitus appears to be feasible in
the United Kingdom when using audiological support. Randomized controlled trials
to further investigate the effectiveness of iCBT for tinnitus in the United
Kingdom are required.
PMID- 28418329
TI - Phoneme Error Pattern by Heritage Speakers of Spanish on an English Word
Recognition Test.
AB - BACKGROUND: Heritage speakers acquire their native language from home use in
their early childhood. As the native language is typically a minority language in
the society, these individuals receive their formal education in the majority
language and eventually develop greater competency with the majority than their
native language. To date, there have not been specific research attempts to
understand word recognition by heritage speakers. It is not clear if and to what
degree we may infer from evidence based on bilingual listeners in general.
PURPOSE: This preliminary study investigated how heritage speakers of Spanish
perform on an English word recognition test and analyzed their phoneme errors.
RESEARCH DESIGN: A prospective, cross-sectional, observational design was
employed. STUDY SAMPLE: Twelve normal-hearing adult Spanish heritage speakers
(four men, eight women, 20-38 yr old) participated in the study. Their language
background was obtained through the Language Experience and Proficiency
Questionnaire. Nine English monolingual listeners (three men, six women, 20-41 yr
old) were also included for comparison purposes. DATA COLLECTION AND ANALYSIS:
Listeners were presented with 200 Northwestern University Auditory Test No. 6
words in quiet. They repeated each word orally and in writing. Their responses
were scored by word, word-initial consonant, vowel, and word-final consonant.
Performance was compared between groups with Student's t test or analysis of
variance. Group-specific error patterns were primarily descriptive, but
intergroup comparisons were made using 95% or 99% confidence intervals for
proportional data. RESULTS: The two groups of listeners yielded comparable scores
when their responses were examined by word, vowel, and final consonant. However,
heritage speakers of Spanish misidentified significantly more word-initial
consonants and had significantly more difficulty with initial /p, b, h/ than
their monolingual peers. The two groups yielded similar patterns for vowel and
word-final consonants, but heritage speakers made significantly fewer errors with
/e/ and more errors with word-final /p, k/. CONCLUSIONS: Data reported in the
present study lead to a twofold conclusion. On the one hand, normal-hearing
heritage speakers of Spanish may misidentify English phonemes in patterns
different from those of English monolingual listeners. Not all phoneme errors can
be readily understood by comparing Spanish and English phonology, suggesting that
Spanish heritage speakers differ in performance from other Spanish-English
bilingual listeners. On the other hand, the absolute number of errors and the
error pattern of most phonemes were comparable between English monolingual
listeners and Spanish heritage speakers, suggesting that audiologists may assess
word recognition in quiet in the same way for these two groups of listeners, if
diagnosis is based on words, not phonemes.
PMID- 28418332
TI - Sequential sensory and decision processing in posterior parietal cortex.
AB - Decisions about the behavioral significance of sensory stimuli often require
comparing sensory inference of what we are looking at to internal models of what
we are looking for. Here, we test how neuronal selectivity for visual features is
transformed into decision-related signals in posterior parietal cortex (area
LIP). Monkeys performed a visual matching task that required them to detect
target stimuli composed of conjunctions of color and motion-direction. Neuronal
recordings from area LIP revealed two main findings. First, the sequential
processing of visual features and the selection of target-stimuli suggest that
LIP is involved in transforming sensory information into decision-related
signals. Second, the patterns of color and motion selectivity and their impact on
decision-related encoding suggest that LIP plays a role in detecting target
stimuli by comparing bottom-up sensory inputs (what the monkeys were looking at)
and top-down cognitive encoding inputs (what the monkeys were looking for).
PMID- 28418331
TI - Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues.
AB - The role of the cellular microenvironment in enabling metazoan tissue genesis
remains obscure. Ctenophora has recently emerged as one of the earliest-branching
extant animal phyla, providing a unique opportunity to explore the evolutionary
role of the cellular microenvironment in tissue genesis. Here, we characterized
the extracellular matrix (ECM), with a focus on collagen IV and its variant,
spongin short-chain collagens, of non-bilaterian animal phyla. We identified
basement membrane (BM) and collagen IV in Ctenophora, and show that the
structural and genomic features of collagen IV are homologous to those of non
bilaterian animal phyla and Bilateria. Yet, ctenophore features are more diverse
and distinct, expressing up to twenty genes compared to six in vertebrates.
Moreover, collagen IV is absent in unicellular sister-groups. Collectively, we
conclude that collagen IV and its variant, spongin, are primordial components of
the extracellular microenvironment, and as a component of BM, collagen IV enabled
the assembly of a fundamental architectural unit for multicellular tissue
genesis.
PMID- 28418333
TI - Nonlinear feedback drives homeostatic plasticity in H2O2 stress response.
AB - Homeostatic systems that rely on genetic regulatory networks are intrinsically
limited by the transcriptional response time, which may restrict a cell's ability
to adapt to unanticipated environmental challenges. To bypass this limitation,
cells have evolved mechanisms whereby exposure to mild stress increases their
resistance to subsequent threats. However, the mechanisms responsible for such
adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and
microfluidics to investigate the adaptive response of budding yeast to temporally
controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is
a systems-level property resulting from nonlinearity of H2O2 scavenging by
peroxiredoxins and our study reveals that this regulatory scheme induces a
striking hormetic effect of extracellular H2O2 stress on replicative longevity.
Our study thus provides a novel quantitative framework bridging the molecular
architecture of a cellular homeostatic system to the emergence of nonintuitive
adaptive properties.
PMID- 28418334
TI - Juvenile Idiopathic Arthritis.
AB - Juvenile idiopathic arthritis is the most common chronic rheumatic disease of
unknown aetiology in childhood and predominantly presents with peripheral
arthritis. The disease is divided into several subgroups, according to
demographic characteristics, clinical features, treatment modalities and disease
prognosis. Systemic juvenile idiopathic arthritis, which is one of the most
frequent disease subtypes, is characterized by recurrent fever and rash.
Oligoarticular juvenile idiopathic arthritis, common among young female patients,
is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis.
Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult
rheumatoid arthritis, is seen in less than 10% of paediatric patients.
Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific
for childhood, appears with widespread large- and small-joint involvement.
Enthesitis-related arthritis is a separate disease subtype, characterized by
enthesitis and asymmetric lower-extremity arthritis. This disease subtype
represents the childhood form of adult spondyloarthropathies, with human
leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton
involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash,
accompanied by arthritis, nail pitting and dactylitis. Disease complications can
vary from growth retardation and osteoporosis secondary to treatment and disease
activity, to life-threatening macrophage activation syndrome with multi-organ
insufficiency. With the advent of new therapeutics over the past 15 years, there
has been a marked improvement in juvenile idiopathic arthritis treatment and long
term outcome, without any sequelae. The treatment of juvenile idiopathic
arthritis patients involves teamwork, including an experienced paediatric
rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist
and a physiotherapist. The primary goals of treatment are to eliminate active
disease, to normalize joint function, to preserve normal growth and to prevent
long-term joint damage. Timely and aggressive treatment is important to provide
early disease control. The first-line treatment includes disease-modifying anti
rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with
corticosteroids, used in different dosages and routes (oral, intravenous, intra
articular). Intra-articular application of steroids seems to be an effective
treatment modality, especially in monoarthritis. Biological agents should be
added in the treatment of unresponsive patients. Anti-tumour necrosis factor
agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra,
canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory
agents (abatacept) have been shown to be safe and effective in childhood
patients. Recent studies reported sustained reduction in joint damage with even
complete clinical improvement in paediatric patients, compared to previous data.
PMID- 28418335
TI - Evaluation of Dynamic Disulphide/Thiol Homeostasis in Silica Exposed Workers.
AB - BACKGROUND: Oxidative stress is implicated as one of the main molecular mechanism
underlying silicosis. AIMS: In this study, our aim was to asses the redox status
in occupationally silica-exposed workers, by evaluating the dynamic thiol
disulphide homeostasis. STUDY DESIGN: Case-control study. METHODS: Thirty-six
male workers occupationally exposed to silica particles and 30 healthy
volunteers, working as office workers were included to the study. Posteroanterior
chest radiographs and pulmonary function tests of both groups were evaluated.
Also serum thiol disulphide levels were measured using the spectrophotometric
method described by Erel and Neselioglu. RESULTS: Among the 36 workers that
underwent pulmonary function tests 6 (17%) had obstructive, 7 (19%) had
restrictive, 6 (17%) had obstructive and restrictive signs whereas 17 (47%) had
no signs. The mean PFTs results of silica-exposed workers were significantly
lower than control subjects. The serum disulphide levels of silica-exposed
workers were significantly higher than control subjects (23.84+/-5.89 MUmol/L and
21.18+/-3.44 MUmol/L, respectively p=0.02). CONCLUSION: The serum disulphide
levels, a biomarker of oxidative stress, are found to be higher in silica-exposed
workers.
PMID- 28418336
TI - Intracranial Lesions in Children and Adolescents with Morbid Obesity.
AB - BACKGROUND: Intracranial lesions may affect the hypothalamo-hypophyseal axis and
lead to some neuro-endocrinological dysfunctions (hyperphagia, sleep disorders
and hormonal dysfunctions). There is a very limited number of studies about
childhood obesity and intracranial lesions. AIMS: To evaluate the incidence of
intracranial lesions and its role in clinical symptoms and aetiology in cases
with morbid obesity who have been admitted to the paediatric endocrinology
department with this complaint. STUDY DESIGN: Cross-sectional study. METHODS: A
total of 120 cases admitted to the paediatric endocrinology department with the
complaint of morbid obesity between 2002 and 2015 were included in this study. A
detailed history was taken and a physical examination was performed; biochemical,
hormonal parameters were evaluated. Contrast dynamic magnetic resonance imaging
was performed in order to visualize cranial pathologies. RESULTS: An intracranial
lesions was detected in 16.6% of the patients and 55% of these lesions were
adenoma of the hypophysis. Prolactin levels were increased in six patients but
front hypophyseal hormone levels were within normal range in the rest of the
patients. Growth velocity of the patients was not affected. CONCLUSION: In our
study, the incidence of intracranial lesions in children and adolescents with
morbid obesity was much higher than in the normal population. According to this
data, we are of the opinion that contrast dynamic magnetic resonance imaging is
helpful in children with morbid obesity for the early detection of the mass
before it causes any clinical or neurological symptoms and in the prevention of
future complications.
PMID- 28418337
TI - A Simple Measure to Assess Hyperinflation and Air Trapping: 1-Forced Expiratory
Volume in Three Second / Forced Vital Capacity.
AB - BACKGROUND: Several recent studies have suggested that 1 minus-forced expiratory
volume expired in 3 seconds / forced vital capacity (1-FEV3/FVC) may be an
indicator of distal airway obstruction and a promising measure to evaluate small
airways dysfunction. AIMS: To investigate the associations of 1-FEV3/FVC with the
spirometric measures and lung volumes that assess small airways dysfunction and
reflects hyperinflation and air trapping. STUDY DESIGN: Retrospective cross
sectional study. METHODS: Retrospective assessment of a total of 1110 cases who
underwent body plethysmographic lung volume estimations between a time span from
2005 to 2012. Patients were assigned into two groups: firstly by FEV1/FVC
(FEV1/FVC <70% vs. FEV1/FVC >=70%); secondly by FEV3/FVC < lower limits of normal
(LLN) (FEV3/FVC < LLN vs. FEV3/FVC >= LLN). Spirometric indices and lung volumes
measured by whole-body plethysmography were compared in groups. Also the
correlation of spirometric indices with measured lung volumes were assessed in
the whole-study population and in subgroups stratified according to FEV1/FVC and
FEV3/FVC. RESULTS: Six hundred seven (54.7%) were male and 503 (45.3%) were
female, with a mean age of 52.5+/-15.6 years. Mean FEV3/FVC and 1-FEV3/FVC were
87.05%, 12.95%, respectively. The mean 1-FEV3/FVC was 4.9% in the FEV1/FVC >=70%
group (n=644) vs. 24.1% in the FEV1/FVC <70% group (n=466). A positive
correlation was found between 1-FEV3/FVC and residual volume (r=0.70; p<0.0001),
functional residual capacity-pleth (r=0.61; p<0.0001), and total lung capacity
(r=0.47; p<0.0001). 1-FEV3/FVC was negatively correlated with forced expiratory
flow25-75 (r=-0.84; p<0.0001). The upper limit of 95% confidence interval for 1
FEV3/FVC was 13.7%. 1-FEV3/FVC showed significant correlations with parameters of
air trapping and hyperinflation measured by whole-body plethysmography.
Importantly, these correlations were higher in study participants with FEV1/FVC
<70% or FEV3/FVC < LLN compared to those with FEV1/FVC >=70% or FEV3/FVC >= LLN,
respectively. CONCLUSION: 1-FEV3/FVC can be easily calculated from routine
spirometric measurements. 1-FEV3/FVC is a promising marker of air trapping and
hyperinflation. We suggest that 1-FEV3/FVC is complementary to FEV1/FVC and
recommend clinicians to routinely report and evaluate together with FEV1/FVC
during spirometry.
PMID- 28418338
TI - Diagnosis of Nipple Discharge: Value of Magnetic Resonance Imaging and
Ultrasonography in Comparison with Ductoscopy.
AB - BACKGROUND: Pathologic nipple discharge, which is a common reason for referral to
the breast imaging service, refers to spontaneous or bloody nipple discharge that
arises from a single duct. The most common cause of nipple discharge is benign
breast lesions, such as solitary intraductal papilloma and papillomatosis.
Nevertheless, in rare cases, a malignant cause of nipple discharge can be found.
AIMS: To study the diagnostic value of ultrasonography, magnetic resonance
imaging, and ductoscopy in patients with pathologic nipple discharge, compare
their efficacy, and investigate the importance of magnetic resonance imaging in
the diagnosis of intraductal pathologies. STUDY DESIGN: Diagnostic accuracy
study. METHODS: Fifty patients with pathologic nipple discharge were evaluated by
ultrasonography and magnetic resonance imaging. Of these, 44 ductoscopic
investigations were made. The patients were classified according to magnetic
resonance imaging, ultrasonography, and ductoscopy findings. A total of 25
patients, whose findings were reported as intraductal masses, underwent surgery
oincluding endoscopic excision for two endoscopic excision. Findings were
compared with the pathology results that were accepted as the gold standard in
the description of the aetiology of nipple discharge. In addition, magnetic
resonance imaging, ultrasonography and ductoscopy findings were analysed
comparatively in patients who had no surgery. RESULTS: Intraductal masses were
reported in 26 patients, 20 of whom operated and established accurate diagnosis
of 18 patients on magnetic resonance imaging. According to the ultrasonography,
intraductal masses were identified in 22 patients, 17 of whom underwent surgery.
Ultrasonography established accurate diagnoses in 15 patients. Intraductal mass
was identified in 22 patients and ductoscopy established accurate diagnoses based
on histopathologic results in 16 patients. The sensitivities of methods were 75%
in ultrasonography, 90% in magnetic resonance imaging, and 94.6% in ductoscopy.
The specificities were 66.7% in ultrasonography, 66.7% in magnetic resonance
imaging, and 40% in ductoscopy. Intraductal papillomas were mostly observed as
oval nodules with well-circumscribed smooth margins within dilated ducts and
persistant in the dynamic analysis. Lesions that protruded into the lumen of the
ducts, either solitary or multiple, were characteristic ductoscopy findings of
our patients who were diagnosed as having papilloma/papillomatosis. CONCLUSION:
Magnetic resonance imaging and ductoscopy had no statistical superiority over
each other, however they were superior to ultrasonography in the diagnosis of
pathologic nipple discharge. Magnetic resonance imaging may be highly sensitive
for diagnosing nipple discharge with new techniques and sequences and a non
invasive method that more advantageous for showing ductal tree visualization and
is able to detect completely obstructed intraductal lesions.
PMID- 28418339
TI - Fetal Nasal Bone Length as a Novel Marker for Prediction of Adverse Perinatal
Outcomes in the First-Trimester of Pregnancy.
AB - BACKGROUND: Adverse outcomes of pregnancy are a challenging health-care problem.
Prediction of adverse pregnancy outcomes is important to prevent the morbidities
of the foetus and the mother. AIMS: To study the clinical interest of fetal nasal
bone length in predicting adverse pregnancy outcomes in the first trimester of
pregnancy. STUDY DESIGN: A population-based retrospective cohort study. METHODS:
Data from 868 women with first-trimester fetal nasal bone length and birth
records available were enrolled. Fetal nasal bone length percentiles were
determined and evaluated for their ability to predict adverse pregnancy outcomes
such as preterm birth, preterm labour, preterm premature rupture of membranes,
early preterm birth, gestational diabetes mellitus, gestational hypertension
preeclampsia, small-for-gestational age foetuses, macrosomia, oligohydramnios,
polyhydramnios and fetal distress. RESULTS: Fetal nasal bone length >95th
percentile was significantly associated with preterm labor and preterm premature
rupture of membranes (p=0.02, accuracy 0.91 and p=0.001, accuracy 0.94,
respectively), whereas nasal bone length >99th percentile was significantly
associated with preterm labor and oligohydramnios (p=0.006, accuracy 0.95 and
p=0.014, accuracy 0.97). CONCLUSION: Fetal nasal bone length at high percentiles
in the first trimester of pregnancy may aid in the prediction of adverse outcomes
such as preterm labour, preterm premature rupture of membranes and
oligohydramnios.
PMID- 28418340
TI - Risk Adapted Management of Febrile Neutrepenia and Early Cessation of Empirical
Antibiotherapy in Hematopoietic Stem Cell Transplantation Setting.
AB - BACKGROUND: Haematopoietic stem cell transplantation is a curative treatment
option for many haematological disorders. Infection following haematopoietic stem
cell transplantation is one of the major causes of mortality. AIMS: To
investigate the outcomes of early cessation of empirical antibiotic treatment per
protocol in febrile neutropenia patients who have undergone haematopoietic stem
cell transplantation at our clinic. STUDY DESIGN: Descriptive study. METHODS: The
present study retrospectively evaluated febrile neutropenia attacks in
haematopoietic stem cell transplantation recipients during the period June 2014 -
January 2015 at our haematopoietic stem cell transplantation clinic. RESULTS: A
total of 72 febrile neutropenia attacks were evaluated in 53 patients. In 46
febrile neutropenia attacks, microbiologic cultures revealed positive results. In
culture-positive febrile neutropenia episodes a single bacterium was isolated in
32 cases and multiple strains were isolated in 14. In 15 patients, empirical
antibiotic therapy was discontinued after 72 hours. These patients were
clinically stable, without evident focus of infection and had negative culture
results. Only 4 recurrent episodes were observed (27%) after cessation of
antibiotherapy. No patient died as a result of recurrent infection. The 30-day
and 100-day post-transplantation mortality rates of patients with febrile
neutropenia episodes were 11.3% (6/53) and 3.8% (2/53), respectively. Infection
related 30-day and 100-day mortality rates were 7.5% (4/53) and 0% (0/53),
respectively. CONCLUSION: The main message of our study is that early cessation
of empirical antibiotherapy seems to be feasible in eligible patients without
increasing febrile neutropenia mortality rates.
PMID- 28418341
TI - The Knowledge Level and Opinions of Physicians about the Medical and Legal
Procedures Related to Physical Child Abuse.
AB - BACKGROUND: In order to diagnose child abuse, physicians need to consider the
possibility of abuse in every child they encounter, have sufficient information
about the topic and manage the cases according to current law. AIMS: To determine
the knowledge level of physicians on child abuse and to learn their opinions
about the procedures when they suspect child abuse. STUDY DESIGN: A questionnaire
(cross-sectional) study. METHODS: A detailed questionnaire was applied to 390
physicians of whom 233 were general practitioners. The first part of the
questionnaire included demographic variables (age, gender, occupational
experience) and the frequency of child physical abuse cases encountered, since
that is the most easily diagnosed and proven form of abuse. The second part
consisted of 32 questions about diagnosis of physical child abuse and procedures
during the follow-up of the cases. Statistical analyses were performed using SPSS
version 18.0. RESULTS: Of the participating physicians, 47.4% (n=185) were female
and only 13.1% of the physicians had some kind of postgraduate training on child
abuse. The correct response rate of specialists compared to general practitioners
was significantly higher. A total of 263 (72.3%) physicians thought that there
was a specific law on physical child abuse in the Turkish Republic. More than two
thirds of physicians thought that reporting should only be addressed to Social
Services and physicians should not be obliged to report to law enforcement.
CONCLUSION: The results of the present study adds to the already known necessity
for better training of physicians about physical child abuse and the need to
refresh their knowledge through postgraduate courses. According to current
regulations, it is obligatory to report abuse cases to the public prosecutor
and/or police, therefore physicians also need training in respect of the legal
status and medico-legal approach to these cases.
PMID- 28418342
TI - Transsexual Mastectomy: Selection of Appropriate Technique According to Breast
Characteristics.
AB - BACKGROUND: Subcutaneous mastectomy for female- to-male transsexuals is usually
the first surgical pro- cedure in sexual reassignment. The main objective of
subcutaneous mastectomy is to create an aesthetically pleasing male chest contour
by removing all glandular tissue while minimizing chest wall scars. AIMS: In this
paper, we present our experience with subcutaneous mastectomy performed in female
to- male transsexual patients. The authors recommend their point of view to aid
in selecting the most suitable subcutaneous mastectomy technique depending on
breast characteristics. STUDY DESIGN: Retrospective cross-sectional study.
METHODS: Between March 2011 and December 2014, 52 patients underwent bilateral
subcutaneous mastec- tomies (total of 104 mastectomies), performed using the
following four techniques: Webster semicircular, concentric circular, vertical,
and apron flap. The tech- nique decision depended on the breast size, degree of
skin excess, skin elasticity, chest width, nipple areolar complex size and
position. RESULTS: Seventeen patients (32.7%) were operated with Webster
semicircular, 7 patients (13.5%) with con- centric periareolar, 12 patients with
vertical (23%); and 16 patients (30.8%) with the apron flap technique. The
overall postoperative complication rate was 13.4%. All patients were satisfied
with the aesthetic results of their subcutaneous mastectomies within the follow
up period. CONCLUSION: To obtain higher patient satisfaction with aesthetic
results and lower postoperative complication rates, breast characteristics are
evaluated in a detailed fashion, while choosing the ideal technique of Female-to
Male (FtM) subcutaneous mastectomy. The presented surgical new algorithm
facilitates the selection of the most reliable surgical technique.
PMID- 28418343
TI - The Use of Human Epididymis 4 and Cancer Antigen 125 Tumor Markers in the Benign
or Malignant Differential Diagnosis of Pelvic or Adnexal Masses.
AB - BACKGROUND: Ovarian cancer is one of the highest mortality cancers in
gynaecology. Discrimination of benign masses from malignant ones may sometimes
become a challenge for the clinician since there is not a reliable tumour marker,
thus some unnecessary, highly morbid operations can be performed. AIMS: To
explore the efficacy of human epididymis 4 (HE 4) and cancer antigen 125 (CA 125)
markers in differentiating malignant and benign pelvic masses of ovarian origin
and to identify the cut-off points for those markers. STUDY DESIGN: Prospective
study. METHODS: Fifty-one patients who were diagnosed and planned to undergo
surgery for ovarian mass between June 2008 and December 2008 were enrolled into
this study. Preoperative venous blood samples were taken and frozen for marker
investigation and final diagnoses were concluded by histopathological
examination. After recruitment of all cases CA 125 and HE 4 levels were
evaluated. RESULTS: The statistical analysis did not indicate any statistically
significant difference between the CA 125 levels of the patients with malignant
and benign adnexal masses (p=0.105). The HE 4 levels of the patients with
malignant adnexal masses were higher at a statistically significant level
compared to the patients with benign adnexal masses (p=0.002). For HE 4 tumour
marker and at the cut-off point of >25 pM, sensitivity was 1, specificity 0.40,
positive cut-off value 0.19, negative cut-off value 1, accuracy 0.47 and positive
likelihood ratio 1.65. CONCLUSION: Human epididymis 4 is a better diagnostic tool
than CA 125 in benign-malignant discrimination of adnexal masses. The cut-off
value of 25 pmol/L for human epididymis 4 will contribute to providing proper
guidance to patients with adnexal masses and applying the proper treatment
method.
PMID- 28418344
TI - Rare Giant Angiokeratoma of the Vulva: A Case Report.
AB - BACKGROUND: Angiokeratoma of fordyce occurring over on the vulva is a rare
condition. Fordyce angiokeratoma is observed more frequently among men than
women. In women, it is generally observed in later life, and appears as multiple
dark purple papules, measuring 2-4 mm, on the vulva. CASE REPORT: We present the
case of a 17-year-old white teenage girl with giant Fordyce angiokeratoma on the
right vulva. The angiokeratoma was removed and a V-Y advancement flap was made.
CONCLUSION: In the literature, this is the first childhood case reported in which
a reconstruction of the vulva was performed.
PMID- 28418345
TI - Cricotracheal Resection in a Patient with Severe Subglottic Stenosis - Advantages
of a Temporary Non-Cannulated Tracheostomy.
AB - BACKGROUND: Stenosis in the area of the cricotracheal segment is still a
challenging problem to be dealt with. Post-intubational cases mark an increase in
recent years due to the advances in intensive care, thoracic surgery and
neurosurgery departments. CASE REPORT: This paper describes a case report of a
patient with severe subglottic stenosis (grade III according to the Cotton-Myer
scale), introduces a new option in cricotracheal resections - postoperative
temporary non-cannulated tracheostomy and describes its advantages. CONCLUSION:
This variation of classical operative techniques provides additional fixation of
the trachea, thus relieving any transitory tension on the anastomosis; acts as a
valve and decreases the air-pressure in the upper airways during coughing and
sneezing in the post-operative period; and is an easy access point for video
tracheoscopy of the anastomosis.
PMID- 28418346
TI - Extra-Gastrointestinal Stromal Tumor of Prostate.
AB - BACKGROUND: Extra-gastrointestinal stromal tumor is defined as a mesenchymal
neoplasm arising from soft tissues outside the gastrointestinal tract. Prostatic
extra-gastrointestinal stromal tumor has rarely been noted. CASE REPORT: A 56
year-old man presented with pain in the anal region. A digital rectal examination
revealed that the prostate was markedly enlarged with a smooth, bulging surface.
Computerized tomography images showed a 6 cm heterogeneous, infiltrative tumor
within the prostate gland extending to the trigon of the bladder, left seminal
vesicle and rectum. The tru-cut biopsy of the prostate was reported as leiomyoma.
It was decided to perform surgery and the masses were easily and completely
removed from the adjacent structures. The case was reported as extra
gastrointestinal stromal tumor within the intermediate- risk category with free
surgical margins. Four years after the surgery, a locoregional failure was
observed and treated with imatinib. CONCLUSION: Stromal tumor, although rare,
should be considered in the differential diagnosis in patients with an enlarged
prostate.
PMID- 28418347
TI - Difficult Cases of Odontogenic Deep Neck Infections: A Report of Three Patients.
AB - BACKGROUND: Deep neck infections are important otolaryngologic emergencies due to
serious complications and the risk of airway compromise, which can lead to
mortality. Although the most common causes among pediatric patients are
tonsillitis and pharyngeal infections, odontogenic infections are an important
cause in adults. CASE REPORT: We present three patients with multiple deep neck
space abscess formation due to odontogenic infection. Two of them required
tracheotomy due to airway compromise, and one had mediastinitis. CONCLUSION: An
underestimated tooth infection can cause hazardous complications such as
mediastinitis and respiratory distress requiring tracheotomy.
PMID- 28418348
TI - Para Phimosis Leading to Glans Gangrene - A Devastating Preventable Complication.
PMID- 28418349
TI - Retrograde Gastric Intussusception.
PMID- 28418350
TI - Femoral Adamantinoma: A Rare Lesion in an Elderly Patient in a Rare Location.
PMID- 28418351
TI - [Connexin 43 expression in human brain glial tumors].
AB - AIM: To conduct an immunohistochemical (IHC) study of the expression of connexin
43 in the samples of glial tumors of various grades: gemistocytic astrocytomas
(Grade 2), oligodendrogliomas (Grade 2) and glioblastomas (Grade 4). MATERIAL AND
METHODS: The material investigated was fragments of human brain glial tumors
(grade 2 gemistocytic astrocytomas (n=2), grade 2 oligodendrogliomas (n=2), and
grade 4 glioblastomas (n=14) and those of tumor-surrounding tissue (n=4). The
material was fixed in 10% buffered formalin, dehydrated, and embedded in paraffin
according to the standard technique. IHC studies of the slices applied primary
rabbit polyclonal antibodies against connexin 43 ('Spring Bioscience', USA) and
the Dako EnVision + Peroxidase (DAB) visualization system ('Dako', Denmark).
After the immunohistochemical reaction, the cell nuclei were stained with Mayer's
hematoxylin. RESULTS: Immunohistochemistry showed the changing pattern of
connexin 43 expression as compared with intact tissue in the glial tumors.
Instead of the fine-granular expression in the thin cellular processes in the
neuropil, the tumors mainly displayed a coarse-grained cytoplasmic and even
nuclear reaction. The morphology and localization of positive structures depended
on the variant of an examined tumor. In addition, the most malignant brain
gliomas generally exhibited a reduction in the expression of connexin 43, i.e.
its quantity is inversely proportional to the degree of malignancy of the tumor.
CONCLUSION: The low connexin 43 expression levels may reflect both a reduction in
astroglial functional gap junctions and semicanals and a decrease in the amount
of the protein itself that has independently antioncogenic properties. The
observed cytoplasmic and nuclear expression of connexin 43 is most likely to be
associated with the aberrant activity of a number of kinases, such as proto
oncogene tyrosine-kinase Src or protein kinase C (PKC).
PMID- 28418352
TI - [Fatty acid synthase in the diagnosis of prostate neoplasms].
AB - : The differential diagnosis of benign and malignant changes in the prostate
presents still definite difficulties; the antibody panel existing for these
purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme
required for de novo lipogenesis. A number of studies have noted increased
expression of the gene encoding this protein in tumors and precancerous lesions
of different locations. AIM: To estimate the diagnostic value of analyzing the
expression of FASN in prostate neoplasias. MATERIAL AND METHODS: Surgical
specimens were selected for study from 71 patients with prostate cancer during
radical prostatectomy. An immunohistochemical method was used to analyze FASN
expression. RESULTS: The expression of FASN was observed to be moderate or
intensive in adenocarcinoma and high-grade prostatic intraepithelial neoplasia
(hPIN) in all the study samples while 2 cases showed none and weak expression of
AMACR. In benign lesions, the expression of this protein was identified only in 3
cases and it was characterized by a low-intensity staining. CONCLUSION: The study
has shown that the high frequency of FASN expression in hPIN and cancer and no
expression in most structures of benign hyperplasia make it possible to use this
protein as an additional marker in the differential diagnosis of prostatic
neoplasms.
PMID- 28418353
TI - [A change in the expression of membrane-associated proteins and cytoplasmic actin
isoforms in the progression of human colon tumors].
AB - : Tumor progression is a complex process that also involves the restructuring of
the actin cytoskeleton and the weakening of intercellular adhesive contacts due
to the tumor cells that pass through the epithelial-mesenchymal transition (EMT).
AIM: To identify correlations between clinical features, risk of progression
and/or recurrence of human colon adenocarcinomas (CAC), and EMT-related tumor
markers. MATERIAL AND METHODS: Descending colon and sigmoid colon adenocarcinoma
samples were examined immunohistochemically. Formalin-fixed paraffin-embedded
tissue sections were incubated with antigen-specific antibodies, then secondary
antibodies labeled with fluorochromes, and the fluorescence intensity of
microscopy images was analyzed. RESULTS: The cells of a tumor compared to those
of intact colon tissue showed a weak staining of E-cadherin in the cell-cell
contact areas. The reduced membrane staining and nuclear localization of beta
catenin were detected in moderately (G2) and poorly (G3) differentiated tumors.
There were substantially decreased beta-actin levels in almost all tumor samples
and increased gamma-actin ones, mainly in the samples belonging to stage IV
disease. CONCLUSION: A correlation was found between stage, tumor differentiation
grade, risk for relapse or progression of disease, and the impaired expression of
different EMT markers: total or partial loss of E-cadherin expression, beta
catenin reorganization in cell-cell contacts, and a change in the ratio of
cytoplasmic actin isoforms in the late stages of CAC development. We believe that
these molecular markers may have a prognostic potential.
PMID- 28418354
TI - [Clinical and morphological signs of viral damage to a kidney transplant].
AB - AIM: To compare morphological changes and results of immunohistochemical (IHC)
identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in
the biopsy specimens with their clinical manifestations in recipients of renal
transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted
using 71 needle renal transplant biopsy specimens from patients in the study
group and 10 renal biopsy specimens from those in the control group. A number of
clinical indicators were estimated. RESULTS: IHC examination revealed the
expression of adenoviral antigens more commonly in patients with posttransplant
nephritis than in recipients without nephritis or in control individuals
(p<0.05). The association of patient age and time after kidney transplantation
with the severity of viral damage was confirmed: graft loss in children occurred
within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in
patients with the morphological patterns of polyomavirus nephropathy.
Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant
associations with morphological changes. CONCLUSION: By taking into account a
variety of factors that influence the development of viral nephritis,
morphological and IHC examinations should be combined with evaluation of clinical
findings.
PMID- 28418355
TI - [Morphometric features of cardiomyocytes in the ventricular septum of patients
with hypertrophic cardiomyopathy].
AB - AIM: to determine the diameter and length of cardiomyocytes (CMC) in the
ventricular septum (VS) of patients with hypertrophic cardiomyopathy (HCM) and to
analyze correlations of a change in CMC sizes with the anatomical features of the
heart in the patients. MATERIAL AND METHODS: Longitudinal sections of
intraoperative myocardial biopsy specimens taken from 23 patients aged 15-59
years with HCM were treated using immunohistochemical detection of connexin 43;
the sizes of 50 CMCs were measured; a 4-point scale was used to assess the degree
of myofibril loss (MFL) in these cells. The change in the diameter and length of
the cells during their rearrangement as MFL gradually increased, as well as the
correlations of CMC sizes with the anatomical parameters of the heart were
analyzed. RESULTS: VS CMCs from the patients with HCM were hypertrophic and were
in the early stages of rearrangement accompanied by MFL. During this
rearrangement, CMCs in some patients grew in length and, less frequently,
diameter. The average diameter of CMCs was directly correlated with VS thickness.
The average length of the cells in the CMC population with a considerable degree
of MFL also directly correlated with VS thickness. CONCLUSION: The findings could
suggest that the factor raising VS thickness in HCM may be an increase in not
only diameter of CMCs, but also in length of CMCs, which had impaired orientation
in the VS - which are oriented perpendicular to their normal tangential position.
The presence of such CMCs in the VS myocardium in patients with HCM can be
discussed due to the typical large number of myocardial areas with the impaired
parallel arrangement of CMCs.
PMID- 28418356
TI - [Pathomorphology of the ventricular germinal zone and neocortex in newborn
infants with posthemorrhagic hydrocephalus].
AB - AIM: To study the morphological features of the ventricular germinal zone and
neocortex in newborns at 22-40 weeks' gestation with posthemorrhagic
hydrocephalus. MATERIAL AND METHODS: The brains of fetuses and newborns at 22-40
weeks' gestation with posthemorrhagic hydrocephalus (n=12) were examined; a
control group included the brains with a lateral ventricle lumen width of not
more than 0.5 cm (n=30). The investigators conducted a comprehensive
pathomorphological study of the ventricular germinal zone and neocortex in the
projection field No. 6. RESULTS: Posthemorrhagic hydrocephalus is characterized
by a deceleration in the reduction of the ventricular germinal zone and by the
corresponding level of differentiation of the cortex and neurons to gestational
age in the presence of the physiological expression of reelin in the Cajal
Retzius neurons and in that of the impaired expression of matrix
metalloproteinase 9 (a decrease) and the glial protein S-100 (an increase) in the
cells of the ventricular germinal zone. CONCLUSION: The morphological features of
the ventricular germinal zone and neocortex of fetuses and newborns at 22-40
weeks' gestation with posthemorrhagic hydrocephalus should be considered as
morphological differential diagnostic criteria for the disease.
PMID- 28418357
TI - [Renal morphological changes in experimental oxalate nephrolithiasis].
AB - AIM: To evaluate renal morphological changes in the early stages of lithogenic
processes and during urinary correction of urine with oxalate-chelating compounds
(sodium citrate). MATERIAL AND METHODS: An experimental model of oxalate
nephrolithiasis was performed on 80 male Wistar rats weighing 180 to 250 g. Rat
kidneys were morphologically and ultrastructurally studied. Immunohistochemical
techniques were applied to study the features of development of endoplasmic
reticulum stress. RESULTS: There were histotopographic changes in the renal
tissue elements in the early stages of development of lithogenic processes
accompanied by characteristic ultrastructural changes in the epithelium of the
renal tubules and collecting ducts: by expansion of elements in the granular
endoplasmic network, by mitochondrial damage with formation of large, ampullary
extended cristae, and by emergence of autolysosomes. Signs of development of
endoplasmic reticulum stress with activation of protein GADD153 were found, which
deteriorated the cell lining of the nephron tubules and collecting ducts.
CONCLUSION: In the early stages of development of lithogenic processes, there are
stereotypic ultrastructural and histotopographic changes in the epithelium of the
nephron tubules and collecting ducts, which contribute to the progression of
stone formation processes and to the disruption of cellular homeostasis with
activation of endoplasmic reticulum stress, synthesis impairment, or post
translational modifications in modulator proteins of lithogenesis.
PMID- 28418358
TI - [Tumors of the kidney. The new 2016 WHO classification of tumors of the
genitourinary system].
AB - The article deals with the innovations available in the 2016 World Health
Organization (WHO) classification of renal tumors, which has replaced the
previous 2004 WHO classification. The review highlights the key aspects necessary
for practicing histopathologists who work in specialized cancer centers or
multidisciplinary hospitals diagnosing renal tumors. How to choose a system for
determining the malignancy grade of renal tumors is considered separately.
PMID- 28418359
TI - [A rare concurrence of polymyalgia rheumatica and AA-amyloidosis].
AB - Polymyalgia rheumatica (PMR) is a rare chronic inflammatory disease. It
predominantly affects the elderly. The disease has a slow onset, pain and
stiffness in the muscles of the shoulder and pelvic girdle, fever, weight loss,
and a high acute-phase inflammatory response. The disease is concurrent with
giant cell arteritis in a quarter of cases, which allows some authors to consider
them as two different manifestations of the same pathological process. The
kidneys are rarely involved. This disease is rarely complicated by AA
amyloidosis. The authors describe a case of RPM in a patient who has developed
secondary AA amyloidosis.
PMID- 28418360
TI - [Role of telocytes in the heart in health and diseases].
AB - This review summarizes the data available in the literature on the development,
structure, and function of telocytes (TCs) and their role in the heart in health
and diseases. At the present time, TCs have been found in many organs of mammals
and humans. TC is a small oval cell that contains a nucleus surrounded by small
amounts of cytoplasm, with extremely long and thin processes named telopodias.
TCs have unique ultrastructural and immunohistochemical features; double positive
labeling for CD34/PDGFR-beta and CD34/vimentin is suitable for their
identification. The role of TCs in the heart at different study stages is the
subject of debate. There are currently available data on a decline in the number
of cardiac TCs in patients with various heart diseases. Relying on a number of
investigations showing that TCs are present in the subepicardial stem cell
niches, the authors consider a hypothesis for the key role of cardiac TCs in the
regeneration and reparation of the heart.
PMID- 28418361
TI - [Intraoperative formation of the valved conduit in aortic root surgery].
AB - AIM: To present an experience of intraoperative manufacture of the valved conduit
in aortic root surgery in the Department of Cardiac Surgery of Sechenov First
Moscow State Medical University. MATERIAL AND METHODS: In our department aortic
valve and ascending aortic replacement using intraoperatively manufactured valved
conduit was performed in 11 patients for the period 2012-2016. Technical aspects,
choice of vascular prosthesis size and type of fixation to achieve optimal
hemodynamics and adequate impermeability of stitches are described. RESULTS:
Intraoperative manufacture of the valved conduit is successfully reproducible
technique with good early and remote results. CONCLUSION: Described surgical
method is not accompanied by increased postoperative blood loss, CPB and aortic
cross-clamping time.
PMID- 28418362
TI - [Individual learning curves for microsurgical myocardial revascularization].
AB - AIM: To create individual learning curves for microsurgical myocardial
revascularization. MATERIAL AND METHODS: It was analyzed duration of the
individual stages of the first 100 CABG procedures which were performed using
microsurgical technique and surgical microscope. Graphs reflecting correlation
between duration of the individual surgical stages and their number were framed.
RESULTS: Improvement in distal anastomosis time, aortic cross-clamping time,
cardiopulmonary bypass time and duration of surgery was observed with increased
surgeon's experience. CONCLUSION: Individual learning curves objectively
characterize the learning process of microsurgical myocardial revascularization,
allow to estimate the time need for improvement of cardiac surgeons'
qualification and demonstrate dates for achieving average surgical quality during
learning the technique.
PMID- 28418363
TI - [Correlation of the intra-operative neuromonitoring data and emg-characteristics
of post-operative motor deficit in patients with spinal deformities].
AB - AIM: To correlate electroneuromyigraphic (ENMG) manifestations of post-operative
motor deficit developed in patients after spinal deformity correction with
qualitative evaluation of the severity of intra-operative pyramidal disorders
according to protocol of intra-operative neuromonitoring (IONM). MATERIAL AND
METHODS: ENMG data of 87 patients aged 6-43 years with spinal deformities of
different etiology were analyzed before and after surgical correction and were
correlated with intra-operative neuromonitoring course. RESULTS: We have
identified five types of the intraoperative reaction of pyramidal system to
surgical aggression. Severity of postoperative motor deficit was the most
pronounced after the fifth type of reaction according to electromyography
(complete prolonged oppression of motor evoked potentials). CONCLUSION: We
suggested the scale of intra-operative pyramidal disorders severity that is
satisfactorily correlated with functional surgical outcomes which are reflected
in the dynamics of particular and integral characteristics of voluntary and
evoked bioelectrical activity of the lower limb muscles. This fact makes possible
to use safely the above-mentioned protocol for IONM, to predict postoperative
motor disorders and to formulate reasonably the recommendations for postoperative
management.
PMID- 28418364
TI - [Evolution of complex treatment of patients with non-specific pleural empyema].
AB - AIM: To analyze long-term own experience of NPE treatment in view of evolution of
surgical sanitation of pleural cavity. MATERIAL AND METHODS: The analysis
included 5115 patients with NPE for the last 39 years (1977-2015). Morbidity,
features of microflora of purulent exudate, changes in the structure of surgical
methods were assessed. The role of computed tomography in the diagnostic
algorithm and treatment of NPE was studied. RESULTS: The evolution of NPE
surgical management includes introduction of video technologies, thermal surgical
instruments and widespread use of computed tomography in the diagnosis of pleural
empyema. So, significant reduction of patients who were discharged with residual
cavities was observed. Postoperative mortality was 19.5% for the period 1977-1996
when traumatic open surgery was used. At the same time there were no deaths
within 1997-2015 due to introduction of VATS pleural drainage. Overall mortality
decreased from 4.9% to 3.2% for the same period due to reduced postoperative
complications. CONCLUSION: The introduction of minimally invasive technologies,
new thermal surgical instruments changed management of NPE patients, reduced the
number of traumatic open procedures. So, improved outcomes were achieved.
PMID- 28418365
TI - [Surgical strategy for locally-advanced right-sided colonic cancer].
AB - AIM: To present early and remote surgical outcomes in patients with locally
advanced right-sided colonic cancer, invasion of pancreatic head and/or duodenal
wall. MATERIAL AND METHODS: Early and remote surgical outcomes were analyzed in
27 patients who underwent gastropancreatoduodenectomy combined with right-sided
hemicolectomy (ileotransversostomy extirpation) for locally-advanced right-sided
colonic cancer. RESULTS: Mean time of surgery was 300 (240-460) minutes,
intraoperative blood loss - 2000 (500-7200) ml. Postoperative complications were
observed in 15 (55.6%) patients. 3 (11.1%) patients died in early postoperative
period. Overall 1-, 3- and 5-year survival was 92.7%, 48% and 36,5% respectively.
Median was 33 months. CONCLUSION: Advanced combined surgery for locally-advanced
right-sided colonic cancer, invasion of pancreatic head and/or duodenal wall is
associated with acceptable incidence of postoperative complications, early and
long-term mortality.
PMID- 28418366
TI - [The role of 3D-CT in surgery for pancreatic ductal adenocarcinoma: post
processing and tissue volume calculation].
AB - AIM: To define the indications for pancreatoduodenectomy using 3D CT-imaging, to
calculate the volume of damaged and intact tissues and to determine type of
surgery depending on severity of disease in case of ductal pancreatic
adenocarcinoma. MATERIAL AND METHODS: Retrospective analysis of CT-scans of 30
patients with ductal pancreatic adenocarcinoma was performed. In groups 1 and 2
by 15 patients total pancreatectomy and pancreatoduodenectomy were made
respectively. All patients underwent contrast-enhanced CT examination (Brilliance
iCT, Phillips) followed post-processing on Brilliance Workspace Portal platform.
All data were assessed by two reviewers. RESULTS: In group 1 CT volume of the
tumor was 24+/-19 cm3 (32% of total pancreas), in group 2 - 9.8+/-6 cm3 (16% of
total pancreas). CT-volume of celiacomesenteric arteries and portal system was
25.8+/-10 mm/59.5+/-18.9 mm and 23.3+/-6/49.9+/-14.7 mm in groups 1 and 2
respectively. Greater volume of tumor was significantly associated with increased
portal system (p<0.03). Sensitivity, specificity and accuracy of determining of
tumor location were increased up to 94%, 50% and 80% respectively in group 1.
There were no cases of wrong localization in group 2. Data of both reviewers were
similar. CONCLUSION: Total pancreatectomy is advisable for pancreatic
adenocarcinoma if its volume is over 31.8% of total pancreas according to 3D CT
scans. 3D-modeling improves preoperative assessment of resectability, accuracy of
determining of tumor localization and identifying vascular invasion.
PMID- 28418367
TI - [The use of computed tomography in the diagnosis of acute appendicitis].
AB - AIM: To present the use of computed tomography in the diagnosis of acute
appendicitis. MATERIAL AND METHODS: The study was conducted in 139 patients who
were hospitalized with suspected acute appendicitis. However, the diagnosis was
not clearly confirmed by clinical and ultrasonic data. RESULTS: Computed
tomography confirmed/rejected presumptive diagnosis in 90.8% of patients. It was
concluded that CT has high diagnostic accuracy to confirm acute appendicitis.
PMID- 28418368
TI - [Differentiated approach to the treatment of large hernial defects of the
anterior abdominal wall in children (clinical observations)].
AB - AIM: To present an experience of treatment of children with large hernial defects
of the anterior abdominal wall. MATERIAL AND METHODS: This article describes
management of 43 children with large (n=31) and giant (n=12) ventral hernia who
were at N.F. Filatov Children's City Hospital #13 for the period 2005-2015. All
patients underwent surgical correction using local tissues in 'edge to edge'
fashion (n=23), aponeurosis dublication of 'coat floors' type (n=14) and
biological implant 'Permacol' (n=6). Etiological causes of ventral hernias in
children were comprehensively analyzed. Optimal time for surgical treatment and
features of viscero-abdominal disproportion were discussed. CONCLUSION: Early
restoration of anatomical and functional structures of the anterior abdominal
wall is necessary for good cosmetic result and prevention of recurrent ventral
hernia. We presented three clinical examples of commonly used surgical procedures
in children including anterior abdominal wall repair using biological material
'Permacol'.
PMID- 28418369
TI - [Optimization of tissue reparation at treatment by Remaxol].
AB - AIM: Studying influence of remaxol on reparative process of tissue reparation in
a laparotomy wound. MATERIAL AND METHODS: 90 patients with the acute appendicitis
complicated by local peritonitis in the early postoperative period are examined.
50 patients received traditional therapy. Therapy of other 40 patients included
Remaxol (intravenous introduction, daily within 5 days, of 400 ml). RESULTS AND
CONCLUSION: It is established that Remaxol optimizes the course of reparative
process in laparotomy wound that was confirmed with data of tenziomety and wound
exudate cytological research. Efficiency of a Remaxol is based on its capability
to improve microcirculation, antiedematous action and its capability to reduce
excessive intensity peroxide oxidation of membrane lipids, phospholipase activity
and the phenomena of a hypoxia.
PMID- 28418370
TI - [Current study aimed to highlight extent of clot resolution in deep veins and its
association with anticoagulation pattern in VTE patients].
AB - MATERIAL AND METHODS: Data of 70 patients with acute VTE of lower extremities
(iliofemoral level) was analyzed. There were 42 patients in the study group which
were treated with rivaroxaban (15 mg BID for 21 days, 20 mg od from day 22); 28
patients were in control group treated with conventional therapy (LMWH/VKA).
Extent of clot resolution was assessed on ultrasound. Data was collected at a day
of VTE diagnosis and further at 1, 3, 6 month. RESULTS: The results of the study
demonstrated, that patients treated with rivaroxaban had earlier recanalization
and extent of clot resolution was higher than in patients treated with
conventional therapy. After one year of treatment 73,8% of patients in the study
group had total or good recanalization compared to 37% of patients in the control
group.
PMID- 28418371
TI - [Intersphincteric resection for stage I-III low rectal cancer is an oncologically
safe alternative to extralevator abdomino-perineal rectal resection].
AB - AIM: To compare oncologic efficiency of intersphincteric resections and
extralevator abdominoperineal excisions in surgical treatment of low rectal
cancer. METHODS: Between 2006 and 2015 in Department of colorectal and pelvic
floor surgery (Russian scientific center of surgery n.a. acad. B.V. Petrovsky)
and in Clinic of Colorectal and Minimally invasive surgery (Sechenov First Moscow
State Medical University) 40 consecutive patients underwent intersphincteric
resection (ISR) and 31 underwent extralevator abdominoperineal excision (EAPE).
All patients had low rectal cancer staged I-III within 5 cm from the anal verge.
RESULTS: Circular resection margin >1 mm was achieved in 95% and 84% of patients
after ISR and EAPR correspondingly (p=0.002), negative distal resection margin
was achieved in 95% of ISR patients. In ISR group mean distance from the lower
tumor edge to the distal resection margin was 1,17+/-0,78 cm. Colo-anal
anastomosis leak rate was 17%. The 3-year disease-free survival in ISR group was
97%, 5-year disease-free survival was 93%. The 5-year disease-free survival in
stage III for ISR group was 71,4%. In 98% of ISR patients complete restoration of
bowel continuity was performed.
PMID- 28418373
TI - [Surgical strategy in rectal resection for cancer].
PMID- 28418372
TI - [The current view for antisecretory therapy in acute pancreatitis].
PMID- 28418374
TI - [Intestinal fistula after anterior abdominal wall hernia repair with composite
prosthesis].
PMID- 28418375
TI - [Technical aspects in surgery for acute adhesive intestinal obstruction].
PMID- 28418376
TI - A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop
formation.
AB - Circular RNAs (circRNAs) are a diverse and abundant class of hyper-stable, non
canonical RNAs that arise through a form of alternative splicing (AS) called back
splicing. These single-stranded, covalently-closed circRNA molecules have been
identified in all eukaryotic kingdoms of life1, yet their functions have remained
elusive. Here, we report that circRNAs can be used as bona fide biomarkers of
functional, exon-skipped AS variants in Arabidopsis, including in the homeotic
MADS-box transcription factor family. Furthermore, we demonstrate that circRNAs
derived from exon 6 of the SEPALLATA3 (SEP3) gene increase abundance of the
cognate exon-skipped AS variant (SEP3.3 which lacks exon 6), in turn driving
floral homeotic phenotypes. Toward demonstrating the underlying mechanism, we
show that the SEP3 exon 6 circRNA can bind strongly to its cognate DNA locus,
forming an RNA:DNA hybrid, or R-loop, whereas the linear RNA equivalent bound
significantly more weakly to DNA. R-loop formation results in transcriptional
pausing, which has been shown to coincide with splicing factor recruitment and
AS2-4. This report presents a novel mechanistic insight for how at least a subset
of circRNAs probably contribute to increased splicing efficiency of their cognate
exon-skipped messenger RNA and provides the first evidence of an organismal-level
phenotype mediated by circRNA manipulation.
PMID- 28418378
TI - Polysaccharide structure: A hint from gut bacteria.
PMID- 28418377
TI - The Magnaporthe oryzae nitrooxidative stress response suppresses rice innate
immunity during blast disease.
AB - Understanding how microorganisms manipulate plant innate immunity and colonize
host cells is a major goal of plant pathology. Here, we report that the fungal
nitrooxidative stress response suppresses host defences to facilitate the growth
and development of the important rice pathogen Magnaporthe oryzae in leaf cells.
Nitronate monooxygenases encoded by NMO genes catalyse the oxidative
denitrification of nitroalkanes. We show that the M. oryzae NMO2 gene is required
for mitigating damaging lipid nitration under nitrooxidative stress conditions
and, consequently, for using nitrate and nitrite as nitrogen sources. On plants,
the Deltanmo2 mutant strain penetrated host cuticles like wild type, but invasive
hyphal growth in rice cells was restricted and elicited plant immune responses
that included the formation of cellular deposits and a host reactive oxygen
species burst. Development of the M. oryzae effector-secreting biotrophic
interfacial complex (BIC) was misregulated in the Deltanmo2 mutant. Inhibiting or
quenching host reactive oxygen species suppressed rice innate immune responses
and allowed the Deltanmo2 mutant to grow and develop normally in infected cells.
NMO2 is thus essential for mitigating nitrooxidative cellular damage and, in rice
cells, maintaining redox balance to avoid triggering plant defences that impact
M. oryzae growth and BIC development.
PMID- 28418379
TI - Exercise contagion in a global social network.
AB - We leveraged exogenous variation in weather patterns across geographies to
identify social contagion in exercise behaviours across a global social network.
We estimated these contagion effects by combining daily global weather data,
which creates exogenous variation in running among friends, with data on the
network ties and daily exercise patterns of ~1.1M individuals who ran over 350M
km in a global social network over 5 years. Here we show that exercise is
socially contagious and that its contagiousness varies with the relative activity
of and gender relationships between friends. Less active runners influence more
active runners, but not the reverse. Both men and women influence men, while only
women influence other women. While the Embeddedness and Structural Diversity
theories of social contagion explain the influence effects we observe, the
Complex Contagion theory does not. These results suggest interventions that
account for social contagion will spread behaviour change more effectively.
PMID- 28418380
TI - Crop breeding: Turning a lawn into a field.
PMID- 28418381
TI - Sparse panicle1 is required for inflorescence development in Setaria viridis and
maize.
AB - Setaria viridis is a rapid-life-cycle model panicoid grass. To identify genes
that may contribute to inflorescence architecture and thus have the potential to
influence grain yield in related crops such as maize, we conducted an N-nitroso-N
methylurea (NMU) mutagenesis of S. viridis and screened for visible inflorescence
mutant phenotypes. Of the approximately 2,700 M2 families screened, we identified
four recessive sparse panicle mutants (spp1-spp4) characterized by reduced and
uneven branching of the inflorescence. To identify the gene underlying the sparse
panicle1 (spp1) phenotype, we performed bulked segregant analysis and deep
sequencing to fine map it to an approximately 1 Mb interval. Within this
interval, we identified disruptive mutations in two genes. Complementation tests
between spp1 and spp3 revealed they were allelic, and deep sequencing of spp3
identified an independent disruptive mutation in SvAUX1 (AUXIN1), one of the two
genes in the ~1 Mb interval and the only gene disruption shared between spp1 and
spp3. SvAUX1 was found to affect both inflorescence development and root
gravitropism in S. viridis. A search for orthologous mutant alleles in maize
confirmed a very similar role of ZmAUX1 in maize, which highlights the utility of
S. viridis in accelerating functional genomic studies in maize.
PMID- 28418383
TI - Marking HIV.
PMID- 28418382
TI - Structure of the hexagonal surface layer on Caulobacter crescentus cells.
AB - Many prokaryotic cells are encapsulated by a surface layer (S-layer) consisting
of repeating units of S-layer proteins. S-layer proteins are a diverse class of
molecules found in Gram-positive and Gram-negative bacteria and most archaea1-5.
S-layers protect cells from the outside, provide mechanical stability and also
play roles in pathogenicity. In situ structural information about this highly
abundant class of proteins is scarce, so atomic details of how S-layers are
arranged on the surface of cells have remained elusive. Here, using purified
Caulobacter crescentus' sole S-layer protein RsaA, we obtained a 2.7 A X-ray
structure that shows the hexameric S-layer lattice. We also solved a 7.4 A
structure of the S-layer through electron cryotomography and sub-tomogram
averaging of cell stalks. The X-ray structure was docked unambiguously into the
electron cryotomography map, resulting in a pseudo-atomic-level description of
the in vivo S-layer, which agrees completely with the atomic X-ray lattice model.
The cellular S-layer atomic structure shows that the S-layer is porous, with a
largest gap dimension of 27 A, and is stabilized by multiple Ca2+ ions bound near
the interfaces. This study spans different spatial scales from atoms to cells by
combining X-ray crystallography with electron cryotomography and sub-nanometre
resolution sub-tomogram averaging.
PMID- 28418384
TI - Dietary short-chain fatty acids protect against type 1 diabetes.
PMID- 28418385
TI - Speaking out about gender imbalance in invited speakers improves diversity.
PMID- 28418386
TI - Circulating potential.
PMID- 28418388
TI - Glioma immune evasion.
PMID- 28418389
TI - The immune system as a social network.
PMID- 28418387
TI - Mitochondria are the powerhouses of immunity.
AB - Recent evidence indicates that mitochondria lie at the heart of immunity.
Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the
mitochondrial outer membrane is a platform for signaling molecules such as MAVS
in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis,
fusion and fission have roles in aspects of immune-cell activation. Most
important, Krebs cycle intermediates such as succinate, fumarate and citrate
engage in processes related to immunity and inflammation, in both innate and
adaptive immune cells. These discoveries are revealing mitochondrial targets that
could potentially be exploited for therapeutic gain in inflammation and cancer.
PMID- 28418391
TI - Vitamin C for microglia.
PMID- 28418390
TI - IRE1 gives weight to obesity-associated inflammation.
PMID- 28418393
TI - Macrophage dynamics.
PMID- 28418392
TI - Gene-enhancer variants reveal diverse TCR-mediated differentiation.
PMID- 28418394
TI - PD-1 targets CD28.
PMID- 28418395
TI - An analysis of ideal and actual time to surgery after traumatic spinal cord
injury in Canada.
AB - STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon
survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the
timing of decompression/stabilization for spinal cord injury and actual practice.
Discrepancies in surgical timing and barriers to ideal timing of surgery were
explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord
Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical
management. Following data collection, a survey was distributed to Canadian
surgeons, asking for perceived to be the optimal and actual timings of surgery.
Discrepancies between actual data and surgeon survey responses were then compared
using chi2 tests and logistic regression. RESULTS: The majority of injury
patterns identified in the registry were treated operatively. ASIA Impairment
Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR
data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities
between what surgeons identified as ideal, actual current practice and RHSCIR
data were demonstrated. A great majority of surgeons (93.0%) believed surgery
under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS
A/B/C/D injuries. Definitive surgical management within 24 h was actually
accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal
surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was
identified, but not accomplished. Discrepancies between the opinions on the
optimal and actual timing of surgery in tSCI patients suggest the need for
strategies for knowledge translation and reduction of administrative barriers to
early surgery.
PMID- 28418396
TI - Essential gains and health after upper-limb tetraplegia surgery identified by the
International classification of functioning, disability and health (ICF).
AB - STUDY DESIGN: A questionnaire-based survey. OBJECTIVES: To describe functional
gains and health following upper-limb tetraplegia surgery using the International
Classification of Functioning, Disability and Health (ICF) as a reference and to
explore interconnections across different dimensions of functioning and health.
SETTING: A specialized center for advanced reconstruction of extremities at
Sahlgrenska University Hospital, Gothenburg, Sweden. METHODS: Fifty-seven
individuals who participated in a satisfaction survey were included in the
present study. Besides questions concerned with the respondents' satisfaction
with different aspects of surgery, the measures included perceived overall health
status (EQ-VAS) and achieved grip strength. Univariate analyses were used to
explore interconnections between measures. RESULTS: The gains could be
subcategorized and linked to the ICF domains 'mobility', 'self-care',
'communication', 'domestic life', and 'community, social and civic life', with
'handling objects' and 'maneuvering a wheelchair' as the most frequently reported
gains. The mean EQ-VAS score was 67+/-22. No significant correlation was shown
between grip strength and activity gains, nor between grip strength and perceived
overall health. The degree of satisfaction was, however, associated with self
reported overall health among participants. CONCLUSION: The functional gains
achieved after tetraplegia surgery could be applied to the ICF constructs' body
functions/structures and activity with possible implications on participation.
The overall health perception was relatively high and could be linked to the
degree of satisfaction among participants. Muscle strength is not necessarily
transferable to activity performance. This emphasizes the importance of
addressing factors other than strength in the post-surgical rehabilitation and
assessments.
PMID- 28418397
TI - Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune
response in Drosophila and mice.
AB - Immune homeostasis is a prerequisite to protective immunity against
gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling
(tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals)
is indispensable for intestinal immunity against invading bacteria. However, how
this local antimicrobial immune response contributes to inflammatory regulation
remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a
subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF)
complex) are susceptible to infection as a result of hyper-inflammation rather
than bacterial overload. Detailed analysis shows that Bap180 is induced by the
IMD-Relish response to both enteropathogenic and commensal bacteria. Upregulated
Bap180 can feed back to restrain overreactive IMD signalling, as well as to
repress the expression of the pro-inflammatory gene eiger (TNF), a critical step
to prevent excessive tissue damage and elongate the lifespan of flies, under
pathological and physiological conditions, respectively. Furthermore, intestinal
targeting of Baf180 renders mice susceptible to a more aggressive infectious
colitis caused by Citrobacter rodentium. Together, Bap180 and Baf180 serve as a
conserved transcriptional repressor that is critical for the maintenance of
innate immune homeostasis in the intestines.
PMID- 28418398
TI - Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in
women.
AB - Oxytocin may influence various human behaviors and the connectivity across
subcortical and cortical networks. Previous oxytocin studies are male biased and
often constrained by task-based inferences. Here, we investigate the impact of
oxytocin on resting-state connectivity between subcortical and cortical networks
in women. We collected resting-state functional magnetic resonance imaging (fMRI)
data on 26 typically developing women 40 min following intranasal oxytocin
administration using a double-blind placebo-controlled crossover design.
Independent components analysis (ICA) was applied to examine connectivity between
networks. An independent analysis of oxytocin receptor (OXTR) gene expression in
human subcortical and cortical areas was carried out to determine plausibility of
direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal
and other subcortical regions, but showed modest expression in cortical areas.
Oxytocin increased connectivity between corticostriatal circuitry typically
involved in reward, emotion, social communication, language and pain processing.
This effect was 1.39 standard deviations above the null effect of no difference
between oxytocin and placebo. This oxytocin-related effect on corticostriatal
connectivity covaried with autistic traits, such that oxytocin-related increase
in connectivity was stronger in individuals with higher autistic traits. In sum,
oxytocin strengthened corticostriatal connectivity in women, particularly with
cortical networks that are involved in social-communicative, motivational and
affective processes. This effect may be important for future work on neurological
and psychiatric conditions (for example, autism), particularly through
highlighting how oxytocin may operate differently for subsets of individuals.
PMID- 28418399
TI - Restoring effects of oxytocin on the attentional preference for faces in autism.
AB - Reduced attentional preference for faces and symptoms of social anxiety are
common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers
anxiolytic functions and enhances eye gaze, facial emotion recognition and neural
correlates of face processing in ASD. Here we investigated whether a single dose
of oxytocin increases attention to faces in ASD. As a secondary question, we
explored the influence of social anxiety on these effects. We tested for
oxytocin's effects on attention to neutral faces as compared to houses in a
sample of 29 autistic individuals and 30 control participants using a dot-probe
paradigm with two different presentation times (100 or 500 ms). A single dose of
24 IU oxytocin was administered in a randomized, double-blind placebo-controlled,
cross-over design. Under placebo, ASD individuals paid less attention to faces
presented for 500 ms than did controls. Oxytocin administration increased the
allocation of attention toward faces in ASD to a level observed in controls.
Secondary analyses revealed that these oxytocin effects primarily occurred in ASD
individuals with high levels of social anxiety who were characterized by
attentional avoidance of faces under placebo. Our results confirm a positive
influence of intranasal oxytocin on social attention processes in ASD. Further,
they suggest that oxytocin may in particular restore the attentional preference
for facial information in ASD individuals with high social anxiety. We conclude
that oxytocin's anxiolytic properties may partially account for its positive
effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and
facial emotion recognition.
PMID- 28418400
TI - Short telomere length is associated with impaired cognitive performance in
European ancestry cohorts.
AB - The association between telomere length (TL) dynamics on cognitive performance
over the life-course is not well understood. This study meta-analyses
observational and causal associations between TL and six cognitive traits, with
stratifications on APOE genotype, in a Mendelian Randomization (MR) framework.
Twelve European cohorts (N=17 052; mean age=59.2+/-8.8 years) provided results
for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive
function, mini-mental state exam (MMSE), processing speed by digit symbol
substitution test (DSST), visuospatial functioning, memory and executive
functioning (STROOP). In addition, a genetic risk score (GRS) for TL including
seven known genetic variants for TL was calculated, and used in associations with
cognitive traits as outcomes in all cohorts. Observational analyses showed that
longer telomeres were associated with better scores on DSST (beta=0.051 per s.d.
increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE
(beta=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (beta=-0.053; 95%
CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE E4 non
carriers (beta=0.081; 95% CI: 0.045, 0.117; P=1.0 * 10-5), whereas carriers
performed better in STROOP (beta=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal
associations were found for STROOP only (beta=-0.598 per s.d.-increase of TL; 95%
CI: -1.125, -0.072; P=0.026), with a larger effect in E4-carriers (beta=-0.699;
95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE
summary statistics showed causal effects between TL and general cognitive
function and DSST, but not with STROOP. In conclusion, we suggest causal effects
from longer TL on better cognitive performance, where APOE E4-carriers might be
at differential risk.
PMID- 28418401
TI - Weak associations between pubertal development and psychiatric and behavioral
problems.
AB - Pubertal development has been associated with adverse outcomes throughout
adolescence and adulthood. However, much of the previous literature has
categorized outcome variables and pubertal timing measures for ease of mean
difference or odds ratio interpretation. We use a UK-representative sample of
over 5000 individuals drawn from the Twins Early Development Study to extend this
literature by adopting an individual differences approach and emphasizing effect
sizes. We investigate a variety of psychiatric and behavioral measures collected
longitudinally at ages 11, 14 and 16, for multiple raters and for males and
females separately. In addition, we use two measures of pubertal development: the
Pubertal Development Scale at each age, as well as the age of menarche for girls.
We found that pubertal development, however assessed, was linearly associated
with a range of psychiatric and behavioral outcomes; however, the effect sizes of
these associations were modest for both males and females with most correlations
between -0.10 and 0.10. Our systematic analysis of associations between pubertal
development, and psychiatric and behavioral problems is the most comprehensive to
date. The results showing linearity of the effects of pubertal development
support an individual differences approach, treating both pubertal development
and associated outcomes as continuous rather than categorical variables. We
conclude that pubertal development explains little variance in psychiatric and
behavioral outcomes (<1% on average). The small effect sizes indicate that the
associations are weak and should not warrant major concern at least in non
clinical populations.
PMID- 28418402
TI - Transcriptome sequencing study implicates immune-related genes differentially
expressed in schizophrenia: new data and a meta-analysis.
AB - We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on
lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia
cases and 660 controls, and found 1058 genes to be differentially expressed by
affection status. These differentially expressed genes were enriched for
involvement in immunity, especially the 697 genes with higher expression in
cases. Comparing the current RNAseq transcriptomic profiling to our previous
findings in an array-based study of 268 schizophrenia cases and 446 controls
showed a highly significant positive correlation over all genes. Fifteen (18%) of
the 84 genes with significant (false discovery rate<0.05) expression differences
between cases and controls in the previous study and analyzed here again were
differentially expressed by affection status here at a genome-wide significance
level (Bonferroni P<0.05 adjusted for 8141 analyzed genes in total, or P<~6.1 *
10-6), all with the same direction of effect, thus providing corroborative
evidence despite each sample of fully independent subjects being studied by
different technological approaches. Meta-analysis of the RNAseq and array data
sets (797 cases and 1106 controls) showed 169 additional genes (besides those
found in the primary RNAseq-based analysis) to be differentially expressed, and
provided further evidence of immune gene enrichment. In addition to strengthening
our previous array-based gene expression differences in schizophrenia cases
versus controls and providing transcriptomic support for some genes implicated by
other approaches for schizophrenia, our study detected new genes differentially
expressed in schizophrenia. We highlight RNAseq-based differential expression of
various genes involved in neurodevelopment and/or neuronal function, and discuss
caveats of the approach.
PMID- 28418403
TI - Assessing the presence of shared genetic architecture between Alzheimer's disease
and major depressive disorder using genome-wide association data.
AB - Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in
older age and frequently co-occur. Numerous phenotypic studies based on clinical
diagnoses suggest that a history of depression increases risk of subsequent AD,
although the basis of this relationship is uncertain. Both illnesses are
polygenic, and shared genetic risk factors could explain some of the observed
association. We used genotype data to test whether MDD and AD have an overlapping
polygenic architecture in two large population-based cohorts, Generation
Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25
118), and whether age of depression onset influences any relationship. Using two
complementary techniques, we found no evidence that the disorders are influenced
by common genetic variants. Using linkage disequilibrium score regression with
genome-wide association study (GWAS) summary statistics from the International
Genomics of Alzheimer's Project, we report no significant genetic correlation
between AD and MDD (rG=-0.103, P=0.59). Polygenic risk scores (PRS) generated
using summary data from International Genomics of Alzheimer's Project (IGAP) and
the Psychiatric Genomics Consortium were used to assess potential pleiotropy
between the disorders. PRS for MDD were nominally associated with participant
recalled AD family history in GS:SFHS, although this association did not survive
multiple comparison testing. AD PRS were not associated with depression status or
late-onset depression, and a survival analysis showed no association between age
of depression onset and genetic risk for AD. This study found no evidence to
support a common polygenic structure for AD and MDD, suggesting that the
comorbidity of these disorders is not explained by common genetic variants.
PMID- 28418404
TI - A pathway linking reward circuitry, impulsive sensation-seeking and risky
decision-making in young adults: identifying neural markers for new
interventions.
AB - High trait impulsive sensation seeking (ISS) is common in 18-25-year olds, and is
associated with risky decision-making and deleterious outcomes. We examined
relationships among: activity in reward regions previously associated with ISS
during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS
impulsivity and sensation-seeking subcomponents; and risky decision-making in
100, transdiagnostically recruited 18-25-year olds. ISS, anhedonia, anxiety,
depression and mania were measured using self-report scales; clinician
administered scales also assessed the latter four. A post-scan risky decision
making task measured 'risky' (possible win/loss/mixed/neutral) fMRI-task versus
'sure thing' stimuli. 'Bias' reflected risky over safe choices. Uncertain RE
related activity in left ventrolateral prefrontal cortex and bilateral ventral
striatum was positively associated with an ISS composite score, comprising
impulsivity and sensation-seeking-fun-seeking subcomponents (ISSc; P?0.001). Bias
positively associated with sensation seeking-experience seeking (ES; P=0.003).
This relationship was moderated by ISSc (P=0.009): it was evident only in high
ISSc individuals. Whole-brain analyses showed a positive relationship between:
uncertain RE-related left ventrolateral prefrontal cortical activity and ISSc;
uncertain RE-related visual attention and motor preparation neural network
activity and ES; and uncertain RE-related dorsal anterior cingulate cortical
activity and bias, specifically in high ISSc participants (all ps<0.05, peak
level, family-wise error corrected). We identify an indirect pathway linking
greater levels of uncertain RE-related activity in reward, visual attention and
motor networks with greater risky decision-making, via positive relationships
with impulsivity, fun seeking and ES. These objective neural markers of high ISS
can guide new treatment developments for young adults with high levels of this
debilitating personality trait.
PMID- 28418410
TI - Latin American Society for Pediatric Research (LASPR) Selected Abstracts from the
LIV Annual Meeting.
PMID- 28418406
TI - Large near-term projected snowpack loss over the western United States.
AB - Peak runoff in streams and rivers of the western United States is strongly
influenced by melting of accumulated mountain snowpack. A significant decline in
this resource has a direct connection to streamflow, with substantial economic
and societal impacts. Observations and reanalyses indicate that between the 1980s
and 2000s, there was a 10-20% loss in the annual maximum amount of water
contained in the region's snowpack. Here we show that this loss is consistent
with results from a large ensemble of climate simulations forced with natural and
anthropogenic changes, but is inconsistent with simulations forced by natural
changes alone. A further loss of up to 60% is projected within the next 30 years.
Uncertainties in loss estimates depend on the size and the rate of response to
continued anthropogenic forcing and the magnitude and phasing of internal decadal
variability. The projected losses have serious implications for the hydropower,
municipal and agricultural sectors in the region.
PMID- 28418405
TI - Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal
neuroblast proliferation.
AB - Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction
through enhancement of goal-directed behaviors. However, the contribution of the
A2AR to the control of impulsive reward seeking remains unknown. Using mice that
were exposed to differential reward of low rate (DRL) schedules during Pavlovian
conditioning, second-order schedule discrimination, and the 5-choice serial
reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function
promote impulsive responses. Antagonism of the A2AR lowered ERK1 and ERK2
phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity
during Pavlovian-conditioning and the 5-CSRTT. Remarkably, inhibition of ERK1 and
ERK2 phosphorylation by U0126 in the dHip prior to Pavlovian-conditioning
exacerbated impulsive reward seeking. Moreover, we found decreased A2AR
expression, and reduced ERK1 and ERK2 phosphorylation in the dHip of
equilibrative nucleoside transporter type 1 (ENT1-/-) null mice, which displayed
exacerbated impulsivity. To determine whether impulsive response behavior is
associated with hippocampal neuroblast development, we investigated expression of
BrdU+ and doublecortin (DCX+) following 5-CSRTT testing. These studies revealed
that impulsive behavior driven by inhibition of the A2AR is accompanied by
increased neuroblast proliferation in the hippocampus.
PMID- 28418411
TI - [Groping in the dark: unheard pain 2].
AB - For a very severely mentally disabled, deaf and blind man, it was always very
difficult to carry out dental check-ups, diagnosis and treatment, even with
pharmacologic support. The man cannot communicate pain. When caries and calculus
were diagnosed, the man was treated under general anaesthesia. During this
treatment session he was also found to have severe periodontal disease and peri
apical problems. The legal representative of the patient was unavailable for
consultation on changes to the pre-prepared preliminary treatment plan. This
created a dilemma for the dental treatment team. This case study was presented
during the conference 'State of the art' on March 17, 2017, that was organised by
the Society for the Promotion of Dental Health Care for People with Disabilities
(VBTGG). In this second part of the case, the treatment that was ultimately
chosen is described, considered and discussed.
PMID- 28418413
TI - [How useful is restorative care in the primary dentition?]
AB - Too many children develop carious lesions and many such lesions progress into a
dentine carious lesion. In 2010, the percentage of dentine carious lesions in the
primary dentition of 6-year-old Dutch children that were restored was less than
50 per cent. Owing to research, the necessity to restore dentine carious lesions
routinely has been called into question. Current understanding of cariologic
principles point in the direction of a causal treatment that is based on cleaning
accessible dentine carious cavities and those that can be made accessible,
possibly supported by the application of silver diamine fluoride. The ultimate
goal of a restoration in the primary dentition is to make it possible to remove
biofilm from the tooth surface and to prevent infection of the pulp. If
restoration in primary teeth is necessary, dental practitioners will, in order to
prevent the development of dental anxiety, first have to consider whether it is
feasible to place restorations in an atraumatic manner, for example by means of
the ART method or the Hall technique.
PMID- 28418412
TI - [The family's influence on the oral health of children. A peek behind the front
door].
AB - The prevention of dental caries seems fairly easy. The disease can largely be
avoided by the daily removal of dental plaque using fluoride toothpaste and the
control of sugary intakes. Most parents have sufficient knowledge and motivation
to adhere to this prevention advice with respect to their children. Actual
practice, however, proves quite difficult because parents experience barriers in
implementing the advice. This article provides an overview of the most important
family-related factors that influence children's oral health behaviour and dental
caries experience. Factors include oral health-related attitudes of the parents,
the way that parents deal with their children and communicate with them
(parenting practices) and the organisation of daily life within the family
(family functioning). It's important for oral health care providers to engage in
conversations with parents to identify possible barriers. Tailored advice can
then be given to help them improve their oral health behaviour.
PMID- 28418414
TI - [(Erosive) tooth wear in children and adolescents in the Netherlands: how big is
the problem?]
AB - According to international research, the prevalence of (erosive) tooth wear among
children and adolescents has grown steadily in recent decades. The question was
whether this also applies to the Netherlands and what changes in consumption
patterns may play a role in this development. From 1998 up to and including 2011,
9 studies have been carried out on the prevalence of (erosive) tooth wear among
the young. A meta-analysis of these studies reveals that an increase has also
taken place in the Netherlands. Furthermore, a tendency was found for greater
prevalence with increasing age. It is generally assumed that changes in the
supply of food and drink and therefore consumption patterns have been a major
reason for this increase in children and adolescents. However, longitudinal
studies, in which both the prevalence and incidence of (erosive) tooth wear are
investigated, are needed to support these assumptions. Such studies are, however,
scarce and, moreover, the results show no consistent picture.
PMID- 28418415
TI - [Role of the oral care provider to call attention to child abuse].
AB - The focus on child abuse has increased in recent years. In 2015, the Royal Dutch
Association of Dentists (KNMT) revised the Sign Code 'child abuse and domestic
violence'. The core of the Sign Code is formed by the compulsory 5-step action
plan for the signalling of, among other things, (a suspicion of) child abuse that
must be followed. Dealing professionally with child abuse places high demands on
the knowledge and communication skills of the health care provider. If the
demands are met, the health care provider is by law adequately protected against
complaints. Many health care providers are still uncomfortable about applying the
Sign Code. The number of contacts with Safe at Home for advice and reports coming
from oral care amounts to only a few one-thousandths of the total number of
contacts. In dealing with the neglecting of oral care, the most common form of
child abuse in the area of dental care, professional action is usually still
limited to symptom relief. Organised care via chain formation offers
possibilities for the coordination of targeted action on child abuse.
PMID- 28418416
TI - [Dental treatment of fearful children: subjection, denyal or -guidance?]
AB - Dental treatment anxiety is a common fear among children. The dental health care
provider is faced with difficult dilemmas about ensuring good oral health for
these children in general daily practice. The indicated treatment usually exceeds
the capacity of the frightened child, but when treatment is not performed, the
child is at risk of serious general health problems and its quality of life could
diminish. This article provides an overview of the aetiology of dental treatment
anxiety in children. In addition, the dental practitioner is provided with
insight into the possibilities that allow him/her to enhance the treatability of
the child and reduce anxiety to such an extent that the indicated dental care can
be provided. Psychotherapy and cognitive-behavioural techniques, as well as
pharmacological therapies, are currently considered the most acceptable and
successful treatments for anxiety and phobia. The dental care provider will have
to determine a well-motivated and carefully considered course of treatment,
always keeping in mind the individual context of the child.
PMID- 28418418
TI - Engaging dual donor sites within an N-heterocyclic olefin phosphine ligand.
AB - By investigating the coordination chemistry of a neutral N-heterocyclic olefin
phosphine ligand, a new digold(i) chloride complex was discovered, demonstrating
that mixed element (P/C) donor sites can be accessed at the same time. However
attempts to extend this strategy for the preparation of heterobimetallic
complexes featuring copper(i) and gold(i) centers with this mixed donor ligand
were unsuccessful. The related monometallic copper(i) and gold(i) iodide
complexes were discovered to be emissive in the solid state.
PMID- 28418420
TI - Selective purification and chemical labeling of a target protein on ruthenium
photocatalyst-functionalized affinity beads.
AB - Selective purification and chemical labeling of a target protein in a protein
mixture were simultaneously achieved on the surface of affinity beads
functionalized with ligands, such as benzenesulfonamide and methotrexate (MTX),
and a ruthenium complex containing 2,2'-bipyridine-4,4'-dicarboxylic acid
(dcbpy). Chemical labeling of the target protein with a tyrosine radical trapper
(TRT) proceeded on the surface of the beads when the target protein was in close
proximity to the ruthenium photocatalyst. Both the protein purification and
chemical labeling abilities of the affinity beads functionalized with ruthenium
photocatalyst were not compromised after recycling several times. Dihydrofolate
reductase (DHFR) endogenously expressed in HeLa cells was detected by chemical
labeling with biotin-TRT on the affinity beads with high sensitivity compared to
the conventional silver staining method.
PMID- 28418422
TI - A disease model of diabetic nephropathy in a glomerulus-on-a-chip microdevice.
AB - Diabetic nephropathy is a major chronic renal complication of diabetes mellitus,
and is the leading cause of end-stage kidney diseases. Establishing a disease
model of diabetic nephropathy in vitro can accelerate the understanding of its
mechanisms and pharmaceutical development. We provide the proof-of-principle for
using a glomerulus-on-a-chip microdevice that reconstitutes organ-level kidney
functions to create a human disease model of early stage diabetic nephropathy on
chip. The microfluidic device, which recapitulates the glomerular
microenvironment, consists of parallel channels lined by isolated primary
glomerular microtissues that experience fluid flow to mimic the glomerular
filtration barrier (GFB), including glomerular endothelial cells, 3D basement
membrane and podocytes. This device was used to reproduce high glucose-induced
critical pathological responses in diabetic nephropathy as observed in humans.
The results reveal that hyperglycemia plays a crucial role in the development of
increased barrier permeability to albumin and glomerular dysfunction that lead to
proteinuria. This organ-on-a-chip microdevice mimics the critical pathological
responses of glomerulus that are characteristic of diabetic nephropathy that has
not been possible by cell-based and animal models, providing a useful platform
for studying the mechanism of diabetic nephropathy and developing an effective
therapy in glomerular diseases.
PMID- 28418429
TI - Chemical constituents, radical scavenging activity and enzyme inhibitory capacity
of fruits from Cotoneaster pannosus Franch.
AB - Cotoneaster pannosus (Rosaceae) is a semievergreen shrub, producing globose dark
red pomes, native to China and widely used as an ornamental plant all over the
world. Despite its extensive cultivation, little information is available on the
chemical composition and biological activities of its fruits. In this work, the
analysis of the chemical composition of C. pannosus fruits, in terms of phenolic
components, carotenoids and ascorbic acid by HPLC/DAD, HPLC/ESI-MS and MS/MS as
well as in terms of macro- and micro-nutrients was performed. The fruits proved
to be a good source of shikimic acid and caffeoylquinic acids, whereas beta
carotene, pelargonidin-3-O glucoside and cyanidin-3,5-rutinoside gave an
important contribution to the color of the fruit. Both the polar and apolar fruit
extracts showed noteworthy radical scavenger activity and inhibitory effects
against monoamine oxidase A (MAO-A), tyrosinase (TYR) and alpha-glucosidase,
making C. pannosus red pomes a promising candidate ingredient in functional foods
and dietary supplements.
PMID- 28418430
TI - WAT-on-a-chip: a physiologically relevant microfluidic system incorporating white
adipose tissue.
AB - Organ-on-a-chip systems possess a promising future as drug screening assays and
as testbeds for disease modeling in the context of both single-organ systems and
multi-organ-chips. Although it comprises approximately one fourth of the body
weight of a healthy human, an organ frequently overlooked in this context is
white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety
profiles of a large number of drugs due to their interactions with adipose tissue
and other organs via paracrine signals, fatty acid release, and drug levels
through sequestration. We report a WAT-on-a-chip system with a footprint of less
than 1 mm2 consisting of a separate media channel and WAT chamber connected via
small micropores. Analogous to the in vivo blood circulation, convective
transport is thereby confined to the vasculature-like structures and the tissues
protected from shear stresses. Numerical and analytical modeling revealed that
the flow rates in the WAT chambers are less than 1/100 of the input flow rate.
Using optimized injection parameters, we were able to inject pre-adipocytes,
which subsequently formed adipose tissue featuring fully functional lipid
metabolism. The physiologically relevant microfluidic environment of the WAT-chip
supported long term culture of the functional adipose tissue for more than two
weeks. Due to its physiological, highly controlled, and computationally
predictable character, the system has the potential to be a powerful tool for the
study of adipose tissue associated diseases such as obesity and type 2 diabetes.
PMID- 28418431
TI - Body burdens, sources and interrelations of selected toxic and essential elements
among the nine Cree First Nations of Eeyou Istchee, James Bay region of northern
Quebec, Canada.
AB - BACKGROUND: this article constitutes a report on the comprehensive
Nituuchischaayihtitaau Aschii multi-community environment-and-health study
conducted among the Cree peoples (Eeyouch) of northern Quebec, Canada.
OBJECTIVES: to interpret observed concentrations of a suite of chemical elements
in a multi-media biological monitoring study in terms of sources and predictors.
METHODS: the concentrations of 5 essential and 6 toxic chemical elements were
measured in whole blood, and/or in urine or hair by ICP-MS. Concentrations of
essential elements are compared to those considered normal (i.e., required for
good health) and, when toxic, deemed acceptable at specified concentrations in
public health guidelines. Their dependence on age, sex, the specific community
lived-in and diet were explored employing multivariate analysis of variance
(MANOVA) involving new variables generated by principle component analysis (PCA)
and correspondence analysis (CA). RESULTS: the 5 most prominent PCA axes
explained 67.7% of the variation, compared to 93.0% by 6 main CA factors.
Concentrations of the essential elements in whole blood (WB) and iodine(i) and
arsenic (As) in urine were comparable to those reported in the recent Canadian
Health Measures survey and are assigned to dietary sources. By contrast, WB
cadmium (Cd) was elevated even when smoking was considered. Mercury (Hg)
concentrations in WB and hair were also higher in adults, although comparable to
those observed for other indigenous populations living at northern latitudes.
Fish consumption was identified as the prominent source. Of the 5 coastal
communities, all but one had lower Hg exposures than the four inland communities,
presumably reflecting the type of fish consumed. Use of firearms and smoking were
correlated with WB-lead (Pb). The concentrations of both Hg and Pb increased with
age and were higher in men, while WB-Cd and smoking prevalence were higher in
women when considering all communities. Hg and Pb were low in children and women
of reproductive age, with few exceedances of health guidelines. Although
individuals with T2D had somewhat lower WB-Cd, there is some indication that Cd
may potentiate renal dysfunction in this subgroup. Plots of selected CA axes
grouped those elements expected to be in a normal diet and distinguished them
from those with well-known unique sources (especially Hg and As in hair; and Hg,
Pb and Cd in WB). CONCLUSIONS: the use of multiple biological media in
conjunction with the complementary PCA and CA approaches for constructing
composite variables allowed a more detailed understanding of both the sources of
the essential and toxic elements in body fluids and the dependencies of their
observed concentrations on age, sex, community and diet.
PMID- 28418433
TI - Capsaicin presynaptically inhibits glutamate release through the activation of
TRPV1 and calcineurin in the hippocampus of rats.
AB - Capsaicin is the major ingredient in hot peppers of the plant Capsicum genus with
neuroprotective effects in several preclinical models; its effect on glutamate
release has been investigated in the rat hippocampus using isolated nerve
terminals (synaptosomes) and brain slices. In a synaptosomal preparation,
capsaicin dose-dependently reduced 4-aminopyridine-evoked Ca2+-dependent
glutamate release, with an IC50 of approximately 11 MUM. This inhibition was
blocked by capsazepin, an antagonist of TRPV1, which was found to be colocalized
with the vesicle marker protein synaptophysin in synaptosomes using double
immunostaining. Capsaicin decreased 4-aminopyridine-evoked intrasynaptosomal Ca2+
concentration elevation and the capsaicin-mediated inhibition of glutamate
release was prevented by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel
blocker omega-conotoxin MVIIC, but was not affected by the intracellular Ca2+
release inhibitors dantrolene and CGP37157. Furthermore, capsaicin increased the
4-aminopyridine-induced phosphorylation of protein phosphatase calcineurin and
the calcineurin inhibitor cyclosporine A eliminated the inhibitory effect of
capsaicin on evoked glutamate release. Additionally, capsaicin also reduced the
frequency of miniature excitatory postsynaptic currents without affecting their
amplitude in slice preparations. Together, these results suggest that capsaicin
acts at TRPV1 present on hippocampal nerve terminals to increase calcineurin
activation, which subsequently attenuates voltage-dependent Ca2+ entry to cause a
decrease in evoked glutamate release.
PMID- 28418435
TI - Fullerenes for catalysis: metallofullerenes in hydrogen transfer reactions.
AB - [60]Fullerene hybrids have successfully been used as catalysts in hydrogen
transfer reactions, namely ketone reduction and N-alkylation with alcohols. Due
to their poor solubility in polar solvents, these hybrids behave as
homogeneous/heterogeneous catalysts that can be mechanically separated and reused
several times while the final products do not need chromatographic separation.
PMID- 28418439
TI - Non-symmetrical, potentially redox non-innocent imino NHC pyridine 'pincers' via
a zinc ion template-assisted synthesis.
AB - New non-symmetrical, redox-active imino NHC pyridine pincer ligands, 2-(R1
imidazol-2-ylidene)-6-(R2N[double bond, length as m-dash]CH)-pyridine (R1 = 2,6
diisopropylphenyl (DiPP), R2 = 2,4,6-trimethylphenyl (Mes), 4B; R1 = R2 = DiPP,
4C), have been accessed by a ZnII-promoted modular synthesis involving the
quaternization of R1-imidazole by [Zn(kappaNiminekappaNpyridine)(2-(R2N[double
bond, length as m-dash]CH)-6-bromo-pyridine)Cl2], followed by ZnII removal and
deprotonation of imidazolium pro-ligands. Redox active forms of 4B were
implicated in the two complexes obtained by its reaction with FeBr2/KC8; metrical
data analysis pointed to the occurrence of radical anionic and dianionic redox
states of 4B.
PMID- 28418438
TI - A scalable self-priming fractal branching microchannel net chip for digital PCR.
AB - As an absolute quantification method at the single-molecule level, digital PCR
has been widely used in many bioresearch fields, such as next generation
sequencing, single cell analysis, gene editing detection and so on. However,
existing digital PCR methods still have some disadvantages, including high cost,
sample loss, and complicated operation. In this work, we develop an exquisite
scalable self-priming fractal branching microchannel net digital PCR chip. This
chip with a special design inspired by natural fractal-tree systems has an even
distribution and 100% compartmentalization of the sample without any sample loss,
which is not available in existing chip-based digital PCR methods. A special 10
nm nano-waterproof layer was created to prevent the solution from evaporating. A
vacuum pre-packaging method called self-priming reagent introduction is used to
passively drive the reagent flow into the microchannel nets, so that this chip
can realize sequential reagent loading and isolation within a couple of minutes,
which is very suitable for point-of-care detection. When the number of positive
microwells stays in the range of 100 to 4000, the relative uncertainty is below
5%, which means that one panel can detect an average of 101 to 15 374 molecules
by the Poisson distribution. This chip is proved to have an excellent ability for
single molecule detection and quantification of low expression of hHF-MSC stem
cell markers. Due to its potential for high throughput, high density, low cost,
lack of sample and reagent loss, self-priming even compartmentalization and
simple operation, we envision that this device will significantly expand and
extend the application range of digital PCR involving rare samples, liquid biopsy
detection and point-of-care detection with higher sensitivity and accuracy.
PMID- 28418440
TI - An all-atom molecular dynamics study of the anti-interferon signaling of Ebola
virus: interaction mechanisms of EBOV VP24 binding to Karyopherin alpha5.
AB - Ebola virus (EBOV) is highly lethal due to virally encoded immune antagonists,
and the combination of EBOV VP24 with karyopherin alpha (KPNA) will trigger anti
interferon (IFN) signaling. The crystal structure of VP24-KPNA5 has been proposed
in recent studies, but the precise binding mechanisms are still unclear. In order
to explore the VP24-KPNA5 protein binding micro-mechanisms, Molecular Dynamic
(MD) simulations and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA)
energy calculation are performed. The obtained results show that EBOV VP24
binding to KPNA5 will rigidify their binding-face, and both proteins will be
compacted during binding. According to the analyses of binding free energies of
WT and the eight mutant systems, MUT3 makes the most effective contributions to
the interaction; additionally MUT4, R398A and the double mutant have the second
most effective influence. Hydrogen bond analysis demonstrates that inhibitors
which can interfere with the formation of hydrogen bonds D480-T138, E483-R137 and
D205-R396 will prevent the anti-IFN effect. Meanwhile, by combining the
decomposition of binding free energies (DC) with computational alanine scanning
(CAS) results, it is shown that VP24 residues R137 and T138 will be potential
targets for EBOV VP24 inhibitors, and KPNA5 residues R396, R398, R480, Y477 and
F484 will be potential targets to prevent KPNA5 binding to VP24, which will
ultimately block anti-IFN signaling. Our investigations provide theoretical data
to understand the binding modes of VP24-KPNA5. The precise binding mechanisms of
the complex may shed light on the development of potential novel inhibitors
against EBOV infection.
PMID- 28418441
TI - An integrated anti-arrhythmic target network of a Chinese medicine compound,
Wenxin Keli, revealed by combined machine learning and molecular pathway
analysis.
AB - Wenxin Keli (WK), a Chinese patent medicine, is known to be effective against
cardiac arrhythmias and heart failure. Although a number of electrophysiological
findings regarding its therapeutic effect have been reported, the active
components and system-level characterizations of the component-target
interactions of WK have yet to be elucidated. In the current study, we present
the first report of a new protective effect of WK on suppressing anti-arrhythmic
agent-induced arrhythmias. In a model of isolated guinea pig hearts, rapid
perfusion of quinidine altered the heart rate and prolonged the Q-T interval.
Pretreatment with WK significantly prevented quinidine-induced arrhythmias. To
explain the therapeutic and protective effects of WK, we constructed an
integrated multi-target pharmacological mechanism prediction workflow in
combination with machine learning and molecular pathway analysis. This workflow
had the ability to predict and rank the probability of each compound interacting
with 1715 target proteins simultaneously. The ROC value statistics showed that
97.786% of the values for target prediction were larger than 0.8. We applied this
model to carry out target prediction and network analysis for the identified
components of 5 herbs in WK. Using the 124 potential anti-arrhythmic components
and the 30 corresponding protein targets obtained, an integrative anti-arrhythmic
molecular mechanism of WK was proposed. Emerging drug/target networks suggested
ion channel and intracellular calcium and autonomic nervous and hormonal
regulation had critical roles in WK-mediated anti-arrhythmic activity. A
validation of the proposed mechanisms was achieved by demonstrating that calaxin,
one of the WK components from Gansong, dose-dependently blocked its predicted
target CaV1.2 channel in an electrophysiological assay.
PMID- 28418442
TI - Network analysis and percolation transition in hydrogen bonded clusters: nitric
acid and water extracted by tributyl phosphate.
AB - Extraction of polar molecules by amphiphilic species results in a complex variety
of clusters whose topologies and energetics control phase behavior and efficiency
of liquid-liquid separations. A computational approach including quantum
mechanical vibrational frequency calculations and molecular dynamics simulation
with intermolecular network theory is used to provide a robust assessment of
extractant and polar solute association through hydrogen bonding in the tributyl
phosphate (TBP)/HNO3/H2O/dodecane system for the first time. The distribution of
local topologies of the TBP/HNO3/H2O hydrogen bonded clusters is shown to be
consistent with an equilibrium binding model. Mixed TBP/HNO3/H2O clusters are
predicted that have not been previously observable in experiment due to
limitations in scattering and spectroscopic resolution. Vibrational frequency
calculations are compared with experimental data to validate the experimentally
observed TBP-HNO3-HNO3 Chain structure. At high nitric acid and water loading,
large hydrogen-bonded clusters of 20 to 80 polar solutes formed. The cluster
sizes were found to be exponentially distributed, consistent with a constant
average solute association free energy in that size range. Due to the deficit of
hydrogen bond donors in the predominantly TBP/HNO3 organic phase, increased water
concentrations lower the association free energy and enable growth of larger
cluster sizes. For sufficiently high water concentrations, changes in the cluster
size distribution are found to be consistent with the formation of a percolating
cluster rather than reverse micelles, as has been commonly assumed for the
occurrence of an extractant-rich third phase in metal-free solvent extraction
systems. Moreover, the compositions of the large clusters leading to percolation
agrees with the 1 : 3 TBP : HNO3 ratio reported in the experimental literature
for TBP/HNO3/H2O third phases. More generally, the network analysis of cluster
formation from atomic level interactions could allow for control of phase
behavior in multi-component solutions of species with a variety of hydrogen bond
types.
PMID- 28418443
TI - Inaugural Symposium on Advanced Surgical Techniques in Adult Airway
Reconstruction: Proceedings of the North American Airway Collaborative (NoAAC).
PMID- 28418445
TI - Decision Making in Adrenoleukodystrophy: When Is a Good Outcome Really a Good
Outcome?
PMID- 28418446
TI - Anticoagulation Reversal for Supratherapeutic International Normalized Ratio: A
Teachable Moment.
PMID- 28418444
TI - Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer.
AB - Importance: Germline pathogenic variants in BRCA1 and BRCA2 predispose to an
increased lifetime risk of breast cancer. However, the relevance of germline
variants in other genes from multigene hereditary cancer testing panels is not
well defined. Objective: To determine the risks of breast cancer associated with
germline variants in cancer predisposition genes. Design, Setting, and
Participants: A study population of 65 057 patients with breast cancer receiving
germline genetic testing of cancer predisposition genes with hereditary cancer
multigene panels. Associations between pathogenic variants in non-BRCA1 and non
BRCA2 predisposition genes and breast cancer risk were estimated in a case
control analysis of patients with breast cancer and Exome Aggregation Consortium
reference controls. The women underwent testing between March 15, 2012, and June
30, 2016. Main Outcomes and Measures: Breast cancer risk conferred by pathogenic
variants in non-BRCA1 and non-BRCA2 predisposition genes. Results: The mean (SD)
age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1)
years. The frequency of pathogenic variants in 21 panel genes identified in 41
611 consecutively tested white women with breast cancer was estimated at 10.2%.
After exclusion of BRCA1, BRCA2, and syndromic breast cancer genes (CDH1, PTEN,
and TP53), observed pathogenic variants in 5 of 16 genes were associated with
high or moderately increased risks of breast cancer: ATM (OR, 2.78; 95% CI, 2.22
3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67),
PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88).
Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the
MRE11A, RAD50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair
genes; and NF1 were not associated with increased risks of breast cancer.
Conclusions and Relevance: This study establishes several panel genes as high-
and moderate-risk breast cancer genes and provides estimates of breast cancer
risk associated with pathogenic variants in these genes among individuals
qualifying for clinical genetic testing.
PMID- 28418448
TI - beta-Blocker Exposure in Pregnancy and Risk of Fetal Cardiac Anomalies.
PMID- 28418447
TI - Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain
Fluid With Patient Outcomes.
AB - Importance: Survival rates for head and neck cancer have been relatively stable
for several decades. Individualized prognostic indicators are needed to identify
patients at risk for poorer outcomes. Objective: To determine whether biomarker
levels in surgical drain fluid of patients with head and neck cancer are
associated with poor cancer outcomes. Design, Setting, and Participants: This
prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of
the oral cavity and oropharynx who required surgical treatment from April 1,
2011, to February 1, 2016, at a tertiary or academic care center. Twenty
patients, including 14 with stage IV disease, had complete specimen collection.
Differences in cytokine and MMP levels by disease outcomes were evaluated.
Interventions: Patients underwent surgical treatment with drain placement as
dictated by the standard of care. Drain fluid samples were collected every 8
hours postoperatively until drains were removed because of clinical criteria.
Levels of cytokines and matrix metalloproteinases (MMPs) were measured using
electrochemiluminescent, patterned array, multiplex technology. Main Outcomes and
Measures: The primary clinical outcome measures were survival outcome and
recurrence. The biomarkers measured included the cytokines basic fibroblastic
growth factor, vascular endothelial growth factor isoform A, soluble fms-like
tyrosine kinase-1 (sFlt-1), and placental growth factor (PIGF) and MMP-1, MMP-3,
and MMP-9. Other clinical and pathologic cancer characteristics were recorded.
Results: In this cohort of 20 patients with SCC (15 men and 5 women; mean [SD]
age, 63.5 [9.9] years), a significant association with recurrence was found for
levels of MMP-1 (relative difference between groups, 2.78; 95% CI, 1.23-6.29),
MMP-3 (relative difference between groups, 5.29; 95% CI, 2.14-13.05), and sFlt-1
(relative difference between groups, 3.75; 95% CI, 1.84-7.65). No biomarkers were
associated with disease outcome. Vascular endothelial growth factor isoform A was
associated with nodal metastasis (relative difference between groups, 1.98; 95%
CI, 1.12-3.51), and basic fibroblastic growth factor was associated with
lymphovascular invasion (relative difference between groups, 1.74; 95% CI, 1.02
2.97). Conclusions and Relevance: In this pilot sample of patients with SCC of
the oral cavity and oropharynx, MMP-1, MMP-3, and sFlt-1 levels in wound fluid
were associated with poor clinical cancer outcomes in the form of recurrence.
This finding is consistent with the literature of tumor microenvironment in
saliva, serum, and tumor tissue biomarkers. To our knowledge, this report is the
first of such findings in surgical drain fluid, an easily accessible means of
cytokine measurement. Measurement of these biomarkers in surgical fluid
potentially represents a novel means of assessing cancer prognosis in this
population.
PMID- 28418449
TI - Association of a Communication Training Program With Use of Antipsychotics in
Nursing Homes.
AB - Importance: Off-label antipsychotic prescribing in nursing homes (NHs) is common
and is associated with increased risk of mortality in older adults. Prior large
scale, controlled trials in the NH setting failed to show meaningful reductions
in antipsychotic use. Objective: To quantify the influence of a large-scale
communication training program on NH antipsychotic use called OASIS. Design,
Setting, and Participants: This investigation was a quasi-experimental
longitudinal study of NHs in Massachusetts enrolled in the OASIS intervention.
Participants were residents living in NHs between March 1, 2011, and August 31,
2013. The data were analyzed from December 2015, to March 2016, and from November
through December 2016. Exposures: The OASIS educational program targets all NH
staff (direct care and nondirect care) using a train-the-trainer model. The
program goals were to reframe challenging behaviors of residents with cognitive
impairment as the communication of unmet needs, to train staff to anticipate
resident needs, and to integrate resident strengths into daily care plans. Main
Outcomes and Measures: This study used an interrupted time series model of
facility-level prevalence of antipsychotic medication use, other psychotropic
medication use (antidepressants, anxiolytics, and hypnotics), and behavioral
disturbances to evaluate the intervention's effectiveness in participating
facilities compared with control NHs in Massachusetts and New York. The 18-month
preintervention (baseline) period was compared with a 3-month training period, a
6-month implementation period, and a 3-month maintenance period. Results: This
study included 93 NHs enrolled in the OASIS intervention (27 of which had a high
prevalence of antipsychotic use) compared with 831 nonintervention NHs. Among
OASIS facilities, prevalences of atypical antipsychotic prescribing were 34.1% at
baseline and 26.5% at the study end (absolute reduction of 7.6% and relative
reduction of 22.3%) compared with a drop of 22.7% to 18.8% in the comparison
facilities (absolute reduction of 3.9% and relative reduction of 17.2%). In the
OASIS implementation phase, NHs experienced a reduction in antipsychotic use
prevalence among OASIS facilities (-1.20%; 95% CI, -1.85% to -0.09% per quarter)
greater than that among non-OASIS facilities (-0.23%; 95% CI, -0.47% to 0.01% per
quarter), resulting in a net OASIS influence of -0.97% (95% CI, -1.85% to -0.09%;
P = .03). A difference in trend was not sustained in the maintenance phase
(difference of 0.93%; 95% CI, -0.66% to 2.54%; P = .48). No increases in other
psychotropic medication use or behavioral disturbances were observed. Conclusions
and Relevance: Antipsychotic use prevalence declined during OASIS implementation
of the intervention, but the decreases did not continue in the maintenance phase.
Other psychotropic medication use and behavioral disturbances did not increase.
This study adds evidence for nonpharmacological programs to treat behavioral and
psychological symptoms of dementia.
PMID- 28418450
TI - The Draw(backs) of Big Data.
PMID- 28418452
TI - Multigene Panel Testing and Breast Cancer Risk: Is It Time to Scale Down?
PMID- 28418453
TI - Association of Increasing Nasal Tip Projection With Lip Position in Primary
Rhinoplasty.
AB - Importance: The effects of rhinoplasty maneuvers on adjacent facial features are
an important component in preoperative planning and patient counseling. Tip
projection modifications are commonly performed in both cosmetic and
reconstructive rhinoplasty. Objective: To evaluate the subsequent change in lip
projection that results from increasing nasal tip projection. Design, Setting,
and Participants: In this case series, 20 patients underwent primary rhinoplasty
with the objective of increasing tip projection during the period from October 1,
2014, to September 25, 2015. Preoperative and postoperative photographs were
evaluated. Main Outcomes and Measures: The increased tip projection was verified
using the Goode ratio. Upper lip projection was calculated by the Z angle, which
is based on the intersection between the Frankfort horizontal plane and the
profile line. Vermilion height was also assessed. Results: Of the 20 patients in
the study (19 females and 1 male; mean [SD] age, 26.8 [10.2] years; range, 16-52
years) 18 (90%) demonstrated an increase in upper lip projection when the tip
projection was increased by either a columellar strut or tongue-in-groove
maneuver. The Z angle demonstrated a statistically significant decrease of 2.7
degrees (95% CI, 1.5 degrees -3.9 degrees ; P < .001). Although the vermilion
height did not change a significant amount, there was a trend toward an increase
in mean height of 0.051 (95% CI, -0.00515 to -0.10685; P = .09). Conclusions and
Relevance: Increasing nasal tip projection causes a measurable increase in upper
lip projection. This new causal association has been applied to our filler
injection armamentarium as an alternative way to achieve the desired result of a
more youthful upper lip. Level of Evidence: 4.
PMID- 28418451
TI - Cost-effectiveness of Common Diagnostic Approaches for Evaluation of Asymptomatic
Microscopic Hematuria.
AB - Importance: Asymptomatic microscopic hematuria (AMH) is highly prevalent and may
signal occult genitourinary (GU) malignant abnormality. Common diagnostic
approaches differ in their costs and effectiveness in detecting cancer. Given the
low prevalence of GU malignant abnormality among patients with AMH, it is
important to quantify the cost implications of detecting cancer for each
approach. Objective: To estimate the effectiveness, costs, and incremental cost
per cancer detected (ICCD) for 4 common diagnostic approaches evaluating AMH.
Design, Setting, and Participants: A decision-analytic model-based cost
effectiveness analysis using inputs from the medical literature. PubMed searches
were performed to identify relevant literature for all key model inputs, each of
which was derived from the clinical study with the most robust data and greatest
applicability. Analysis included adult patients with AMH on routine urinalysis
with subgroups of high-risk patients (males, smokers, age >=50 years) seen in the
primary care or urologic referral setting. Interventions: Four diagnostic
approaches were evaluated relative to the reference case of no evaluation: (1)
computed tomography (CT) alone; (2) cystoscopy alone; (3) CT and cystoscopy
combined; and (4) renal ultrasound and cystoscopy combined. Main Outcomes and
Measures: At termination of the diagnostic period, cancers detected, costs (payer
perspective), and ICCD per 10 000 patients evaluated for AMH. Results: Of the 4
diagnostic approaches analyzed, CT alone was dominated by all other strategies,
detecting 221 cancers at a cost of $9 300 000. Ultrasound and cystoscopy detected
245 cancers and was most cost-effective with an ICCD of $53 810. Replacing
ultrasound with CT detected just 1 additional cancer at an ICCD of $6 480 484.
Ultrasound and cystoscopy remained the most cost-effective approach in subgroup
analysis. The model was not sensitive to any inputs within the proposed ranges.
Using probabilistic sensitivity analysis, ultrasound and cystoscopy was the
dominant strategy in 100% of simulations. Conclusions and Relevance: The
combination of renal ultrasound and cystoscopy is the most cost-effective among 4
diagnostic approaches for the initial evaluation of AMH. The use of ultrasound in
lieu of CT as the first-line diagnostic strategy will optimize cancer detection
and reduce costs associated with evaluation of AMH. Given our findings, we need
to critically evaluate the appropriateness of our current clinical practices, and
potentially alter our guidelines to reflect the most effective screening
strategies for patients with AMH.
PMID- 28418454
TI - An Indirect Indentation Method for Evaluating the Linear Viscoelastic Properties
of the Brain Tissue.
AB - Indentation experiments offer a robust, fast, and repeatable testing method for
evaluating the mechanical properties of the solid-state materials in a wide
stiffness range. With the advantage of requiring a minimal sample preparation and
multiple tests on a small piece of specimen, this method has recently become a
popular technique for measuring the elastic properties of the biological
materials, especially the brain tissue whose ultrasoft nature makes its
mechanical characterization very challenging. Nevertheless, some limitations are
associated with the indentation of the brain tissue, such as improper surface
detection, negative initial contact force due to tip-tissue moisture interaction,
and partial contact between the tip and the sample. In this study, an indirect
indentation scheme is proposed to overcome the aforementioned difficulties. In
this way, the indentation force is transferred from a sharp tip to the surface of
the tissue slices via a rigid coverslip. To demonstrate the accuracy of this
method, the linear viscoelastic properties of the white and gray matters of the
bovine brain samples are measured by imposing small cyclic loads at different
frequencies. The rate, regional, directional, and postmortem time dependence of
the viscoelastic moduli are investigated and compared with the previous results
from cyclic shear and monotonic experiments on the brain tissue. While findings
of this research present a comprehensive set of information for the viscoelastic
properties of the brain at a wide frequency range, the central goal of this paper
is to introduce a novel experimentation technique with noticeable advantages for
biomechanical characterization of the soft tissue.
PMID- 28418455
TI - The Development and Performance of After-Hours Primary Care in the Netherlands: A
Narrative Review.
AB - In many Western countries, hospital emergency departments are overcrowded,
leading to the desire to strengthen primary care, particularly after hours. To
achieve this goal, an increasing number of Western nations are reorganizing their
after-hours primary care systems into large-scale primary care physician (PCP)
cooperatives. This article provides an overview of the organization, performance,
and development of PCP cooperatives in the Netherlands. The Dutch after-hours
primary care system might offer opportunities for other countries facing problems
with after-hours care and inappropriate emergency department visits. During the
past several years, the number of contacts with Dutch PCP cooperatives has
increased to 245 contacts per 1000 citizens per year. Many contacts (45%) are
nonurgent, and about half occur as part of a series of primary care contacts. Low
accessibility and availability of daytime primary care are related to greater use
of after-hours primary care. To prevent unnecessary attendance at the
cooperatives, physicians advocate copayment, a stricter triage system, and a
larger role for telephone doctors. More than half of the PCP cooperatives in the
Netherlands have integrated with hospital emergency departments, forming
"emergency care access points." This collaboration has decreased emergency
department use by 13% to 22%, and treatment of self-referrals by PCP cooperatives
in emergency care access points is safe and cost-effective. Direct access to
diagnostic facilities may optimize efficiency even more. Other recent
developments include access to electronic health records of daytime primary care
practices, task substitution from physicians to nurses, and the launch of a 2
year training program for PCPs to become experts in emergency care.
PMID- 28418457
TI - The field of view available to the ventral occipito-temporal reading circuitry.
AB - Skilled reading requires rapidly recognizing letters and word forms; people learn
this skill best for words presented in the central visual field. Measurements
over the last decade have shown that when children learn to read, responses
within ventral occipito-temporal cortex (VOT) become increasingly selective to
word forms. We call these regions the VOT reading circuitry (VOTRC). The portion
of the visual field that evokes a response in the VOTRC is called the field of
view (FOV). We measured the FOV of the VOTRC and found that it is a small subset
of the entire field of view available to the human visual system. For the typical
subject, the FOV of the VOTRC in each hemisphere is contralaterally and foveally
biased. The FOV of the left VOTRC extends ~9 degrees into the right visual field
and ~4 degrees into the left visual field along the horizontal meridian. The FOV
of the right VOTRC is roughly mirror symmetric to that of the left VOTRC. The
size and shape of the FOV covers the region of the visual field that contains
relevant information for reading English. It may be that the size and shape of
the FOV, which varies between subjects, will prove useful in predicting
behavioral aspects of reading.
PMID- 28418456
TI - Mapping the Early Language Environment Using All-Day Recordings and Automated
Analysis.
AB - Purpose: This research provided a first-generation standardization of automated
language environment estimates, validated these estimates against standard
language assessments, and extended on previous research reporting language
behavior differences across socioeconomic groups. Method: Typically developing
children between 2 to 48 months of age completed monthly, daylong recordings in
their natural language environments over a span of approximately 6-38 months. The
resulting data set contained 3,213 12-hr recordings automatically analyzed by
using the Language Environment Analysis (LENA) System to generate estimates of
(a) the number of adult words in the child's environment, (b) the amount of
caregiver-child interaction, and (c) the frequency of child vocal output.
Results: Child vocalization frequency and turn-taking increased with age, whereas
adult word counts were age independent after early infancy. Child vocalization
and conversational turn estimates predicted 7%-16% of the variance observed in
child language assessment scores. Lower socioeconomic status (SES) children
produced fewer vocalizations, engaged in fewer adult-child interactions, and were
exposed to fewer daily adult words compared with their higher socioeconomic
status peers, but within-group variability was high. Conclusions: The results
offer new insight into the landscape of the early language environment, with
clinical implications for identification of children at-risk for impoverished
language environments.
PMID- 28418459
TI - Distribution of Physicians With H-1B Visas By State and Sponsoring Employer.
PMID- 28418460
TI - Marijuana Use During Stages of Pregnancy in the United States.
PMID- 28418458
TI - Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure
Overload: A Computational Study.
AB - Right ventricular failure (RVF) is a lethal condition in diverse pathologies.
Pressure overload is the most common etiology of RVF, but our understanding of
the tissue structure remodeling and other biomechanical factors involved in RVF
is limited. Some remodeling patterns are interpreted as compensatory mechanisms
including myocyte hypertrophy, extracellular fibrosis, and changes in fiber
orientation. However, the specific implications of these changes, especially in
relation to clinically observable measurements, are difficult to investigate
experimentally. In this computational study, we hypothesized that, with other
variables constant, fiber orientation alteration provides a quantifiable and
distinct compensatory mechanism during RV pressure overload (RVPO). Numerical
models were constructed using a rabbit model of chronic pressure overload RVF
based on intraventricular pressure measurements, CINE magnetic resonance imaging
(MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were
conducted under normotensive and hypertensive boundary conditions using
variations in RV wall thickness, tissue stiffness, and fiber orientation to
investigate their effect on RV pump function. Our results show that a
longitudinally aligned myocardial fiber orientation contributed to an increase in
RV ejection fraction (RVEF). This effect was more pronounced in response to
pressure overload. Likewise, models with longitudinally aligned fiber orientation
required a lesser contractility for maintaining a target RVEF against elevated
pressures. In addition to increased wall thickness and material stiffness
(diastolic compensation), systolic mechanisms in the forms of myocardial fiber
realignment and changes in contractility are likely involved in the overall
compensatory responses to pressure overload.
PMID- 28418461
TI - Look. Listen. Receive.: Surrendering to the Art.
PMID- 28418462
TI - Woman With Yellow Palms and Soles.
PMID- 28418463
TI - Errors in Study Group Numbers and Outcome Interpretation.
PMID- 28418465
TI - Nocturnal Polyuria Drug Approved.
PMID- 28418464
TI - Disentangling Maternal Depression and Antidepressant Use During Pregnancy as
Risks for Autism in Children.
PMID- 28418466
TI - Relief for Dust Mite Allergy.
PMID- 28418467
TI - US-EU Drug Inspection Agreement.
PMID- 28418468
TI - Association Between Maternal Use of SSRI Medications and Autism in Their
Children.
PMID- 28418469
TI - Management of Helicobacter pylori Infection.
PMID- 28418471
TI - Why Replacing the ACA Has Republicans in a Tizzy.
PMID- 28418472
TI - The Medical Expert.
PMID- 28418473
TI - Diagnosis of Bacterial Infection Using a 2-Transcript Host RNA Signature in
Febrile Infants 60 Days or Younger.
PMID- 28418474
TI - Comparative Trends in Payment Adjustments Between Safety-Net and Other Hospitals
Since the Introduction of the Hospital Readmission Reduction Program and Value
Based Purchasing.
PMID- 28418475
TI - Changes in Rates of Ventilator-Associated Pneumonia.
PMID- 28418476
TI - Factors Contributing to the Weekend Effect.
PMID- 28418477
TI - Changes in Rates of Ventilator-Associated Pneumonia-Reply.
PMID- 28418478
TI - Factors Contributing to the Weekend Effect.
PMID- 28418479
TI - Associations of Maternal Antidepressant Use During the First Trimester of
Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum
Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring.
AB - Importance: Prenatal antidepressant exposure has been associated with adverse
outcomes. Previous studies, however, may not have adequately accounted for
confounding. Objective: To evaluate alternative hypotheses for associations
between first-trimester antidepressant exposure and birth and neurodevelopmental
problems. Design, Setting, and Participants: This retrospective cohort study
included Swedish offspring born between 1996 and 2012 and followed up through
2013 or censored by death or emigration. Analyses controlling for pregnancy,
maternal and paternal covariates, as well as sibling comparisons, timing of
exposure comparisons, and paternal comparisons, were used to examine the
associations. Exposures: Maternal self-reported first-trimester antidepressant
use and first-trimester antidepressant dispensations. Main Outcomes and Measures:
Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2
SDs below the mean for gestational age), and first inpatient or outpatient
clinical diagnosis of autism spectrum disorder and attention
deficit/hyperactivity disorder in offspring. Results: Among 1 580 629 offspring
(mean gestational age, 279 days; 48.6% female; 1.4% [n = 22 544] with maternal
first-trimester self-reported antidepressant use) born to 943 776 mothers (mean
age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring
were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational
age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum
disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were
diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the
population level, first-trimester exposure was associated with all outcomes
compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI,
1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism
spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention
deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models
that compared siblings while adjusting for pregnancy, maternal, and paternal
traits, first-trimester antidepressant exposure was associated with preterm birth
(OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01
[95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or
attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results
from analyses assessing associations with maternal dispensations before pregnancy
and with paternal first-trimester dispensations were consistent with findings
from the sibling comparisons. Conclusions and Relevance: Among offspring born in
Sweden, after accounting for confounding factors, first-trimester exposure to
antidepressants, compared with no exposure, was associated with a small increased
risk of preterm birth but no increased risk of small for gestational age, autism
spectrum disorder, or attention-deficit/hyperactivity disorder.
PMID- 28418480
TI - Association Between Serotonergic Antidepressant Use During Pregnancy and Autism
Spectrum Disorder in Children.
AB - Importance: Previous observations of a higher risk of child autism spectrum
disorder with serotonergic antidepressant exposure during pregnancy may have been
confounded. Objective: To evaluate the association between serotonergic
antidepressant exposure during pregnancy and child autism spectrum disorder.
Design, Setting, and Participants: Retrospective cohort study. Health
administrative data sets were used to study children born to mothers who were
receiving public prescription drug coverage during pregnancy in Ontario, Canada,
from 2002-2010, reflecting 4.2% of births. Children were followed up until March
31, 2014. Exposures: Serotonergic antidepressant exposure was defined as 2 or
more consecutive maternal prescriptions for a selective serotonin or serotonin
norepinephrine reuptake inhibitor between conception and delivery. Main Outcomes
and Measures: Child autism spectrum disorder identified after the age of 2 years.
Exposure group differences were addressed by inverse probability of treatment
weighting based on derived high-dimensional propensity scores (computerized
algorithm used to select a large number of potential confounders) and by
comparing exposed children with unexposed siblings. Results: There were 35 906
singleton births at a mean gestational age of 38.7 weeks (50.4% were male, mean
maternal age was 26.7 years, and mean duration of follow-up was 4.95 years). In
the 2837 pregnancies (7.9%) exposed to antidepressants, 2.0% (95% CI, 1.6%-2.6%)
of children were diagnosed with autism spectrum disorder. The incidence of autism
spectrum disorder was 4.51 per 1000 person-years among children exposed to
antidepressants vs 2.03 per 1000 person-years among unexposed children (between
group difference, 2.48 [95% CI, 2.33-2.62] per 1000 person-years; hazard ratio
[HR], 2.16 [95% CI, 1.64-2.86]; adjusted HR, 1.59 [95% CI, 1.17-2.17]). After
inverse probability of treatment weighting based on the high-dimensional
propensity score, the association was not significant (HR, 1.61 [95% CI, 0.997
2.59]). The association was also not significant when exposed children were
compared with unexposed siblings (incidence of autism spectrum disorder was 3.40
per 1000 person-years vs 2.05 per 1000 person-years, respectively; adjusted HR,
1.60 [95% CI, 0.69-3.74]). Conclusions and Relevance: In children born to mothers
receiving public drug coverage in Ontario, Canada, in utero serotonergic
antidepressant exposure compared with no exposure was not associated with autism
spectrum disorder in the child. Although a causal relationship cannot be ruled
out, the previously observed association may be explained by other factors.
PMID- 28418481
TI - Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based
on the US Preventive Services Task Force Recommendations vs the ACC/AHA
Guidelines.
AB - Importance: There are important differences among guideline recommendations for
using statin therapy in primary prevention. New recommendations from the US
Preventive Services Task Force (USPSTF) emphasize therapy based on the presence
of 1 or more cardiovascular disease (CVD) risk factors and a 10-year global CVD
risk of 10% or greater. Objective: To determine the difference in eligibility for
primary prevention statin treatment among US adults, assuming full application of
USPSTF recommendations compared with the American College of Cardiology/American
Heart Association (ACC/AHA) guidelines. Design, Setting, and Participants:
National Health and Nutrition Examination Survey (NHANES) data (2009-2014) were
used to assess statin eligibility under the 2016 USPSTF recommendations vs the
2013 ACC/AHA cholesterol guidelines among a nationally representative sample of
3416 US adults aged 40 to 75 years with fasting lipid data and triglyceride
levels of 400 mg/dL or less, without prior CVD. Exposures: The 2016 USPSTF
recommendations vs 2013 ACC/AHA guidelines. Main Outcomes and Measures:
Eligibility for primary prevention statin therapy. Results: Among the US primary
prevention population represented by 3416 individuals in NHANES, the median
weighted age was 53 years (interquartile range, 46-61), and 53% (95% CI, 52%-55%)
were women. Along with the 21.5% (95% CI, 19.3%-23.7%) of patients who reported
currently taking lipid-lowering medication, full implementation of the USPSTF
recommendations would be associated with initiation of statin therapy in an
additional 15.8% (95% CI, 14.0%-17.5%) of patients, compared with an additional
24.3% (95% CI, 22.3%-26.3%) of patients who would be recommended for statin
initiation under full implementation of the 2013 ACC/AHA guidelines. Among the
8.9% of individuals in the primary prevention population who would be recommended
for statins by ACC/AHA guidelines but not by USPSTF recommendations, 55% would be
adults aged 40 to 59 years with a mean 30-year cardiovascular risk greater than
30%, and 28% would have diabetes. Conclusions And Relevance: In this sample of US
adults from 2009-2014, adherence to the 2016 USPSTF recommendations for statin
therapy, compared with the 2013 ACC/AHA guidelines, could lead to a lower number
of individuals recommended for primary prevention statin therapy, including many
younger adults with high mean long-term CVD risk.
PMID- 28418483
TI - Tics and Tourette Syndrome.
PMID- 28418485
TI - The Living Donor: A Tale of Money, Mania, and Clinical Mastery.
PMID- 28418482
TI - Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute
Sore Throat in Adults: A Randomized Clinical Trial.
AB - Importance: Acute sore throat poses a significant burden on primary care and is a
source of inappropriate antibiotic prescribing. Corticosteroids could be an
alternative symptomatic treatment. Objective: To assess the clinical
effectiveness of oral corticosteroids for acute sore throat in the absence of
antibiotics. Design, Setting, and Participants: Double-blind, placebo-controlled
randomized trial (April 2013-February 2015; 28-day follow-up completed April
2015) conducted in 42 family practices in South and West England, enrolled 576
adults recruited on the day of presentation to primary care with acute sore
throat not requiring immediate antibiotic therapy. Interventions: Single oral
dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283). Main
Outcomes and Measures: Primary: proportion of participants experiencing complete
resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours,
duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as
bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to
100, worst imaginable), health care attendance, days missed from work or
education, consumption of delayed antibiotics or other medications, adverse
events. Results: Among 565 eligible participants who were randomized (median age,
34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the
intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65
participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo
group achieved complete resolution of symptoms, for a risk difference of 4.7%
(95% CI, -1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P =
.14). At 24 hours, participants receiving dexamethasone were not more likely than
those receiving placebo to have complete symptom resolution. At 48 hours, 102
participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo
group achieved complete resolution of symptoms, for a risk difference of 8.7%
(95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P =
.03). This difference also was observed in participants not offered delayed
antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%)
and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no
significant differences in any other secondary outcomes. Conclusions and
Relevance: Among adults presenting to primary care with acute sore throat, a
single dose of oral dexamethasone compared with placebo did not increase the
proportion of patients with resolution of symptoms at 24 hours. However, there
was a significant difference at 48 hours. Trial Registration: isrctn.org
Identifier: ISRCTN17435450.
PMID- 28418486
TI - Is It Time to Retire?
PMID- 28418489
TI - Potential Cause of Nodding Syndrome Identified.
PMID- 28418490
TI - Depression Is the Leading Cause of Disability Around the World.
PMID- 28418487
TI - Notice of Retraction and Replacement: Oostdijk et al. Effects of Decontamination
of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A
Randomized Clinical Trial. JAMA. 2014;312(14):1429-1437.
PMID- 28418491
TI - Educating Religious Leaders Increases Male Circumcision Rates in Tanzania.
PMID- 28418493
TI - The Threat of Diagnostic Uncertainty in the Medical Management of Uncomplicated
Appendicitis.
PMID- 28418492
TI - Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of
Coping Skills Education Used With Progressive Tinnitus Management.
AB - Purpose: This randomized controlled trial evaluated, within clinical settings,
the effectiveness of coping skills education that is provided with progressive
tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300
veterans were randomized to either PTM intervention or 6-month wait-list control.
The PTM intervention involved 5 group workshops: 2 led by an audiologist
(teaching how to use sound as therapy) and 3 by a psychologist (teaching coping
skills derived from cognitive behavioral therapy). It was hypothesized that PTM
would be more effective than wait-list control in reducing functional effects of
tinnitus and that there would be no differences in effectiveness between sites.
Results: At both sites, a statistically significant improvement in mean Tinnitus
Functional Index scores was seen at 6 months for the PTM group. Combined data
across sites revealed a statistically significant improvement in Tinnitus
Functional Index relative to wait-list control. The effect size for PTM using the
Tinnitus Functional Index was 0.36 (small). Conclusions: Results suggest that PTM
is effective at reducing tinnitus-related functional distress in clinical
settings. Although effect sizes were small, they provide evidence of clinical
effectiveness of PTM in the absence of stringent research-related inclusion
criteria and with a relatively small number of sessions of cognitive behavioral
therapy.
PMID- 28418494
TI - Prevalence, Natural Course, and Prognostic Role of Refractile Drusen in Age
Related Macular Degeneration.
AB - Purpose: To report prevalence, clinical characteristics, and prognostic
significance of refractile drusen in eyes with intermediate age-related macular
degeneration (AMD). Methods: Presence of refractile drusen by color fundus
photography (CFP), corresponding findings by multimodal imaging, and longitudinal
changes with annual examinations for up to 4 years were analyzed within a
prospective natural history study of 98 eyes with non-late AMD of 98 patients
(Age-Related Eye Disease Study [AREDS] stages 3 and 4). Results: A total of 115
refractile drusen were detected at baseline in 20 eyes (20.4%). Refractile drusen
typically showed hyperreflectivity by infrared (80.9%) and blue (93.9%)
reflectance imaging, appearing more distinct when compared to CFP. Laminar
intense hyperreflectivity of Bruch's membrane was detected in 31 lesions by
spectral-domain optical coherence tomography and was strongly related to atrophy
development (23 out of 31 lesions). Presence of refractile drusen at baseline was
overall associated with later development of geographic atrophy (GA) (9/20 eyes
versus 6/78 eyes, P < 0.001). Spontaneous regression without evident atrophy
occurred in seven lesions. Conclusions: Refractile drusen are a relative common
phenotype in intermediate AMD and appear to confer risk for the development of
late AMD. While not all lesions develop late AMD and regression may also occur,
distinct subphenotypes as identified by multimodal imaging may not only be
visible earlier but also be topographically associated with the risk for GA
development. Recognizing the characteristic pattern on multimodal imaging would
inform physicians for identification of the lesion and its clinical history.
PMID- 28418495
TI - Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive
Congenital Cataracts by Homozygosity Screening.
AB - Purpose: To identify the genetic origins of autosomal recessive congenital
cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis
that most arCC patients in consanguineous families in the Punjab areas of
Pakistan should be homozygous for causative mutations, affected individuals were
screened for homozygosity of nearby highly informative microsatellite markers and
then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped
consanguineous families were screened for mutations in 33 known candidate genes.
Results: Patients in 32 arCC families were homozygous for markers near at least 1
of the 33 known CC genes. Sequencing the included genes revealed homozygous
cosegregating sequence changes in 10 families, 2 of which had the same variation.
These included five missense, one nonsense, two frame shift, and one splice site
mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1,
and CRYBA4. Conclusions: The above results confirm the usefulness of homozygosity
mapping for identifying genetic defects underlying autosomal recessive disorders
in consanguineous families. In our ongoing study of arCC in Pakistan, including
83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide
linkage analysis in unpublished data, and 30 previously reported families,
mutations were detected in approximately 37.1% (43/116) of all families studied,
suggesting that additional genes might be responsible in the remaining families.
The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1
(3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of
the genetic architecture of arCC in the Pakistani population.
PMID- 28418497
TI - Course of Sodium Iodate-Induced Retinal Degeneration in Albino and Pigmented
Mice.
AB - Purpose: To characterize the course of sodium iodate (SI)-induced retinal
degeneration in young adult albino and pigmented mice. Methods: Single
intraperitoneal (IP) injections of SI (25, 50, and 100 mg/kg) were performed in 7
to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was
assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by
optokinetic tracking response, ERG, optical coherence tomography (OCT), and
histologic and immunohistochemical techniques. Results: The 50 mg/kg SI dosage
was selected after dose ranging due to consistent retinal effects and lack of
systemic toxicity. Time-dependent deterioration in retinal function and
morphology was consistently observed between 1 and 4 weeks in all measured
parameters. These include reduction of ERG responses, thinning of retinal layers
as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry
revealed rapid RPE disorganization with loss of tight junctions and markedly
reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone
opsins. Earlier time points displayed variable results, including partial
recovery of visual acuity at 1 week and supranormal ERG cone responses at 24
hours, suggesting possible limitations of early intervention and assessment in
the SI model. Conclusions: A single IP injection of 50 mg/kg SI leads to severe
RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors
in both BALB/c and C57Bl/6J mice. This easily induced and reproducible
noninherited model may serve as a useful tool for seeking and evaluating novel
therapeutic modalities for the treatment of retinal degenerations caused by
primary failure of the RPE.
PMID- 28418498
TI - Suppression by an RAR-gamma Agonist of Collagen Degradation Mediated by Corneal
Fibroblasts.
AB - Purpose: To examine the role of retinoic acid receptor (RAR) isoforms in
interleukin-1beta (IL-1beta)-induced collagen degradation by corneal fibroblasts.
Methods: Primary rabbit corneal fibroblasts embedded in a three-dimensional
collagen gel were incubated with or without all-trans retinoic acid (ATRA), the
RAR-alpha agonist Am580, the RAR-beta agonist AC55649, or the RAR-gamma agonist
R667. Collagen degradation was determined by measurement of hydroxyproline
produced in acid hydrolysates of culture supernatants. Matrix metalloproteinase
(MMP) expression was evaluated by immunoblot analysis and gelatin zymography. The
phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous
nuclear factor (NF)-kappaB inhibitor IkappaB-alpha was examined by immunoblot
analysis. Cell proliferation was measured with a bromodeoxyuridine incorporation
assay, and cell viability was determined by measurement of the release of lactate
dehydrogenase. Results: Interleukin-1beta-induced collagen degradation by corneal
fibroblasts was inhibited by ATRA, Am580, and R667 in a concentration-dependent
manner but was unaffected by AC55649, with the inhibitory effects of ATRA and
R667 being markedly greater than that of Am580. The IL-1beta-induced production
of MMP-1, MMP-2, MMP-3, and MMP-9 by corneal fibroblasts was also inhibited by
R667 in a concentration-dependent manner. R667 inhibited the IL-1beta-induced
phosphorylation of IkappaB-alpha but not that of MAPKs. R667 had no effect on the
proliferation or viability of corneal fibroblasts. Conclusions: The RAR-gamma
agonist R667 suppressed MMP production and thereby inhibited collagen degradation
by corneal fibroblasts exposed to the proinflammatory cytokine IL-1beta. These
effects of R667 may be mediated by the NF-kappaB signaling pathway.
PMID- 28418496
TI - Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal
Dystrophies in 144 Consanguineous Pakistani Families.
AB - Purpose: The Pakistan Punjab population has been a rich source for identifying
genes causing or contributing to autosomal recessive retinal degenerations
(arRD). This study was carried out to delineate the genetic architecture of arRD
in the Pakistani population. Methods: The genetic origin of arRD in a total of
144 families selected only for having consanguineous marriages and multiple
members affected with arRD was examined. Of these, causative mutations had been
identified in 62 families while only the locus had been identified for an
additional 15. The remaining 67 families were subjected to homozygosity exclusion
mapping by screening of closely flanking microsatellite markers at 180 known
candidate genes/loci followed by sequencing of the candidate gene for pathogenic
changes. Results: Of these 67 families subjected to homozygosity mapping, 38
showed homozygosity for at least one of the 180 regions, and sequencing of the
corresponding genes showed homozygous cosegregating mutations in 27 families.
Overall, mutations were detected in approximately 61.8 % (89/144) of arRD
families tested, with another 10.4% (15/144) being mapped to a locus but without
a gene identified. Conclusions: These results suggest the involvement of unmapped
novel genes in the remaining 27.8% (40/144) of families. In addition, this study
demonstrates that homozygosity mapping remains a powerful tool for identifying
the genetic defect underlying genetically heterogeneous arRD disorders in
consanguineous marriages for both research and clinical applications.
PMID- 28418499
TI - Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts
After Filtration Surgery for Glaucoma.
AB - Purpose: To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid
samples taken before and after filtration surgery and S1P-induced human
conjunctival fibroblast (HCF) responses. Methods: Levels of S1P and its related
sphingophospholipids in aqueous fluid obtained immediately before and after
filtration surgery were determined by liquid chromatography-tandem mass
spectrometry. HCFs were used for all in vitro experiments. The expression of five
S1P receptor subtypes in HCFs was examined by quantitative real-time PCR. The
effect of S1P and receptor-specific antagonists on HCF viability and cell
migration was assessed by WST-1 assay and scratch migration assay, respectively.
Differentiation to myofibroblasts and extracellular matrix production was
evaluated by examining changes in F-actin, alpha-smooth muscle actin (alphaSMA),
and collagen expression with immunocytochemistry, Western blotting, and collagen
accumulation assay, respectively. Results: No significant S1P levels in the
aqueous fluid samples were detectable immediately before surgery, but
postoperative levels of several lysophospholipids, including S1P, dehydro-S1P,
and sphingosine, were significantly increased to bioactive concentrations in
aqueous fluid in the blebs (P < 0.0001). mRNA expression of the three main S1P
receptor subtypes was detected in HCFs. Although S1P levels did not influence HCF
proliferation, S1P enhanced cell migration, which could be inhibited by the S1P2
antagonist JTE 013. F-actin, alphaSMA, and collagen expression was significantly
increased by S1P stimulation and was reduced by JTE 013. Conclusions: Bioactive
S1P concentrations were present in the aqueous fluid at the end of filtration
surgery. S1P activated HCFs via S1P2 receptors. These results revealed the
potential of S1P2 antagonists in preventing scarring after glaucoma filtration
surgery.
PMID- 28418501
TI - Cost Effectiveness of Wait Time Reduction in Behavioral Interventions for Autism
Reply.
PMID- 28418502
TI - Tumor Sidedness and Prognosis in Colorectal Cancer: Is Microbiome the Missing
Link?
PMID- 28418500
TI - Risk of Uveitis Among People With Psoriasis: A Nationwide Cohort Study.
AB - Importance: Uveitis has been associated with psoriatic arthritis, but to our
knowledge, the relationship between uveitis and psoriasis is unsettled among
researchers. Objective: To evaluate the risk of incident uveitis among people
with psoriasis. Design, Setting, and Participants: This nationwide, retrospective
cohort study conducted in Taiwan from January 1, 2000, to December 31, 2012
included 147 954 people with psoriasis (including 10 107 with concomitant
psoriatic arthritis and 137 847 without psoriatic arthritis) and 147 954
nonpsoriatic controls. Exposure: Psoriasis. Main Outcomes and Measures: Risk of
incident uveitis. Results: The mean (SD) age of the 295 908 study participants
was 44.4 (19.8) years, and 41.2% (n = 121 878) were women. We found that the
group with severe psoriasis with psoriatic arthritis had the greatest risk of
incident uveitis compared with the nonpsoriatic controls (adjusted hazard ratio,
2.40; 95% CI, 1.90-3.02). The group with severe psoriasis without psoriatic
arthritis and the group with mild psoriasis with psoriatic arthritis also had an
increased risk of incident uveitis (adjusted hazard ratio, 1.42; 95% CI, 1.23
1.64; and 1.42; 95% CI, 1.03-1.96; respectively). However, an increased risk for
incident uveitis with mild psoriasis without psoriatic arthritis was not
identified (adjusted hazard ratio, 1.09; 95% CI, 1.00-1.20). Conclusions and
Relevance: People with severe psoriasis and those with mild psoriasis have an
increased risk of uveitis. Clinicians may use this finding as a guide for uveitis
risk stratification among patients with different inflammatory presentations on
the spectrum of psoriatic disease.
PMID- 28418503
TI - Enhanced Epilepsy Surveillance and Awareness in the Age of Zika.
PMID- 28418504
TI - Alternative Facts Have No Place in Science.
PMID- 28418505
TI - Acute and Painless Monocular Vision Loss in a Human Immunodeficiency Virus
Positive Man.
PMID- 28418506
TI - Divergence Compensatory Optical Flow Method for Blood Velocimetry.
AB - Detailed blood velocity map in the vascular system can be obtained by applying
the optical flow method (OFM) in processing fluoroscopic digital subtracted
catheter angiographic images; however, there are still challenges with the
accuracy of this method. In the present study, a divergence compensatory optical
flow method (DC-OFM), in which a nonzero divergence of velocity is assumed due to
the finite resolution of the image, was explored and applied to the digital
subtraction angiography (DSA) images of blood flow. The objective of this study
is to examine the applicability and evaluate the accuracy of DC-OFM in assessing
the blood flow velocity in vessels. First, an Oseen vortex flow was simulated on
the standard particle image to generate an image pair. Then, the DC-OFM was
applied on the particle image pair to recover the velocity field for validation.
Second, DSA images of intracranial arteries were used to examine the accuracy of
the current method. For each set of images, the first image is the in vivo DSA
image, and the second image is generated by superimposing a given flow field. The
recovered velocity map by DC-OFM agrees well with the exact velocity for both the
particle images and the angiographic images. In comparison with the traditional
OFM, the present method can provide more accurate velocity estimation. The
accuracy of the velocity estimation can also be improved by implementing
preprocess techniques including image intensification, Gaussian filtering, and
"image-shift."
PMID- 28418507
TI - Use of Bayesian Decision Analysis to Minimize Harm in Patient-Centered Randomized
Clinical Trials in Oncology.
AB - Importance: Randomized clinical trials (RCTs) currently apply the same
statistical threshold of alpha = 2.5% for controlling for false-positive results
or type 1 error, regardless of the burden of disease or patient preferences. Is
there an objective and systematic framework for designing RCTs that incorporates
these considerations on a case-by-case basis? Objective: To apply Bayesian
decision analysis (BDA) to cancer therapeutics to choose an alpha and sample size
that minimize the potential harm to current and future patients under both null
and alternative hypotheses. Data Sources: We used the National Cancer Institute
(NCI) Surveillance, Epidemiology, and End Results (SEER) database and data from
the 10 clinical trials of the Alliance for Clinical Trials in Oncology. Study
Selection: The NCI SEER database was used because it is the most comprehensive
cancer database in the United States. The Alliance trial data was used owing to
the quality and breadth of data, and because of the expertise in these trials of
one of us (D.J.S.). Data Extraction and Synthesis: The NCI SEER and Alliance data
have already been thoroughly vetted. Computations were replicated independently
by 2 coauthors and reviewed by all coauthors. Main Outcomes and Measures: Our
prior hypothesis was that an alpha of 2.5% would not minimize the overall
expected harm to current and future patients for the most deadly cancers, and
that a less conservative alpha may be necessary. Our primary study outcomes
involve measuring the potential harm to patients under both null and alternative
hypotheses using NCI and Alliance data, and then computing BDA-optimal type 1
error rates and sample sizes for oncology RCTs. Results: We computed BDA-optimal
parameters for the 23 most common cancer sites using NCI data, and for the 10
Alliance clinical trials. For RCTs involving therapies for cancers with short
survival times, no existing treatments, and low prevalence, the BDA-optimal type
1 error rates were much higher than the traditional 2.5%. For cancers with longer
survival times, existing treatments, and high prevalence, the corresponding BDA
optimal error rates were much lower, in some cases even lower than 2.5%.
Conclusions and Relevance: Bayesian decision analysis is a systematic, objective,
transparent, and repeatable process for deciding the outcomes of RCTs that
explicitly incorporates burden of disease and patient preferences.
PMID- 28418508
TI - Lower Cervical Spine Motion Segment Computational Model Validation: Kinematic and
Kinetic Response for Quasi-Static and Dynamic Loading.
AB - Advanced computational human body models (HBM) enabling enhanced safety require
verification and validation at different levels or scales. Specifically, the
motion segments, which are the building blocks of a detailed neck model, must be
validated with representative experimental data to have confidence in segment
and, ultimately, full neck model response. In this study, we introduce detailed
finite element motion segment models and assess the models for quasi-static and
dynamic loading scenarios. Finite element segment models at all levels in the
lower human cervical spine were developed from scans of a 26-yr old male subject.
Material properties were derived from the in vitro experimental data. The segment
models were simulated in quasi-static loading in flexion, extension, lateral
bending and axial rotation, and at dynamic rates in flexion and extension in
comparison to previous experimental studies and new dynamic experimental data
introduced in this study. Single-valued experimental data did not provide
adequate information to assess the model biofidelity, while application of
traditional corridor methods highlighted that data sets with higher variability
could lead to an incorrect conclusion of improved model biofidelity. Data sets
with continuous or multiple moment-rotation measurements enabled the use of cross
correlation for an objective assessment of the model and highlighted the
importance of assessing all motion segments of the lower cervical spine to
evaluate the model biofidelity. The presented new segment models of the lower
cervical spine, assessed for range of motion and dynamic/traumatic loading
scenarios, provide a foundation to construct a biofidelic model of the spine and
neck, which can be used to understand and mitigate injury for improved human
safety in the future.
PMID- 28418510
TI - Finding Youths at Risk for HIV Infection: Targeted Testing, Universal Testing, or
Both?
PMID- 28418509
TI - Association of Preoperative Calcium and Calcitriol Therapy With Postoperative
Hypocalcemia After Total Thyroidectomy.
AB - Importance: Hypocalcemia is the most common complication after total
thyroidectomy and can result in prolonged hospital admissions and increased
hospital charges. Objective: To determine the effectiveness of preoperative
calcium and calcitriol supplementation in reducing hypocalcemia following total
thyroidectomy. Design, Setting, and Participants: A retrospective cohort study
was conducted at a tertiary care center in 65 patients undergoing total
thyroidectomy by a single surgeon. Patients were divided into 2 groups: those
receiving preoperative as well as postoperative supplementation with calcium
carbonate, 1000 to 1500 mg, 3 times daily and calcitriol, 0.25 to 0.5 ug, twice
daily, and those receiving only postoperative supplementation with those agents
at the same dosages. Data on patients who underwent surgery between January 1,
2008, and December 31, 2011, were acquired, and data analyses were conducted from
March through June 2012, and from October through December 2016. Interventions:
Calcium and calcitriol therapy. Main Outcomes and Measures: Postoperative serum
calcium levels and development of postoperative hypocalcemia. Results: Of the 65
patients who underwent total thyroidectomy 27 (42%) were men; mean (SD) age was
49.7 (16.7) years. Thirty-three patients received preoperative calcium and
calcitriol supplementation, and 32 patients received only postoperative therapy.
In the preoperative supplementation group, 15 of 33 (45%) patients underwent
complete central compartment neck dissection and 11 of 33 (33%) had lateral neck
dissection, compared with 16 of 32 (50%) and 12 of 32 (38%), respectively,
patients without preoperative supplementation. The mean measured serum calcium
level in those without preoperative supplementation vs those with supplementation
are as follows: preoperative, 9.6 vs 9.4 mg/dL (absolute difference, 0.16; 95%
CI, -0.12 to 0.49 mg/dL); 12 hours postoperative, 8.3 vs 8.6 mg/dL (absolute
difference, -0.30; 95% CI, -0.63 to 0.02 mg/dL); and 24 hours postoperative, 8.4
vs 8.5 mg/dL (absolute difference, -0.13; 95% CI, -0.43 to 0.16 mg/dL). In
patients not receiving preoperative supplementation, 5 of 32 (16%) individuals
became symptomatically hypocalcemic vs 2 of 33 (6%) in the preoperative
supplementation group; an absolute difference of 10% (95% CI, -6.6% to 26.3%).
Compared with the group not receiving preoperative supplementation, the mean [SD]
length of stay was significantly shorter in the preoperative supplementation
group (3.8 [1.8] vs 2.9 [1.4] days; absolute difference, -0.9; 95% CI, -1.70 to
0.105 days). Preoperative supplementation resulted in an estimated $2819 savings
in charges per patient undergoing total thyroidectomy. Conclusions and Relevance:
Preoperative calcium and calcitriol supplementation, in addition to routine
postoperative supplementation, was associated with a reduced incidence of
symptomatic hypocalcemia, length of hospital stay, and overall charges following
total thyroidectomy.
PMID- 28418511
TI - Early Palliative Care in Advanced Illness: Do Right by Mama.
PMID- 28418512
TI - A Method for In Vitro TCPC Compliance Verification.
AB - The Fontan procedure is a common palliative intervention for sufferers of single
ventricle congenital heart defects that results in an anastomosis of the venous
return to the pulmonary arteries called the total cavopulmonary connection
(TCPC). Local TCPC and global Fontan circulation hemodynamics are studied with in
vitro circulatory models because of hemodynamic ties to Fontan patient long-term
complications. The majority of in vitro studies, to date, employ a rigid TCPC
model. Recently, a few studies have incorporated flexible TCPC models, but
provide no justification for the model material properties. The method set forth
in this study successfully utilizes patient-specific flow and pressure data from
phase contrast magnetic resonance images (PCMRI) (n = 1) and retrospective pulse
pressure data from an age-matched patient cohort (n = 10) to verify the
compliance of an in vitro TCPC model. These data were analyzed, and the target
compliance was determined as 1.36 +/- 0.78 mL/mm Hg. A method of in vitro
compliance testing and computational simulations was employed to determine the in
vitro flexible TCPC model material properties and then use those material
properties to estimate the wall thickness necessary to match the patient-specific
target compliance. The resulting in vitro TCPC model compliance was 1.37 +/- 0.1
mL/mm Hg-a value within 1% of the patient-specific compliance. The presented
method is useful to verify in vitro model accuracy of patient-specific TCPC
compliance and thus improve patient-specific hemodynamic modeling.
PMID- 28418516
TI - Cost-effectiveness of Wait Time Reduction in Behavioral Interventions for Autism.
PMID- 28418515
TI - Pronation-Supination Motion Is Altered in a Rat Model of Post-Traumatic Elbow
Contracture.
AB - The elbow joint is highly susceptible to joint contracture, and treating elbow
contracture is a challenging clinical problem. Previously, we established an
animal model to study elbow contracture that exhibited features similar to the
human condition including persistent decreased range of motion (ROM) in flexion
extension and increased capsule thickness/adhesions. The objective of this study
was to mechanically quantify pronation-supination in different injury models to
determine if significant differences compared to control or contralateral persist
long-term in our animal elbow contracture model. After surgically inducing soft
tissue damage in the elbow, Injury I (anterior capsulotomy) and Injury II
(anterior capsulotomy with lateral collateral ligament transection), limbs were
immobilized for 6 weeks (immobilization (IM)). Animals were evaluated after the
IM period or following an additional 6 weeks of free mobilization (FM). Total ROM
for pronation-supination was significantly decreased compared to the uninjured
contralateral limb for both IM and FM, although not different from control limbs.
Specifically, for both IM and FM, total ROM for Injury I and Injury II was
significantly decreased by ~20% compared to contralateral. Correlations of
measurements from flexion-extension and pronation-supination divulged that FM did
not affect these motions in the same way, demonstrating that joint motions need
to be studied/treated separately. Overall, injured limbs exhibited persistent
motion loss in pronation-supination when comparing side-to-side differences,
similar to human post-traumatic joint contracture. Future work will use this
animal model to study how elbow periarticular soft tissues contribute to
contracture.
PMID- 28418517
TI - March for Science.
PMID- 28418518
TI - Development of a Research Agenda to Identify Evidence-Based Strategies to Improve
Physician Wellness and Reduce Burnout.
PMID- 28418519
TI - Association of Diet With Skin Histological Features in UV-B-Exposed Mice.
AB - Importance: Long-term exposure to solar radiation produces deleterious photoaging
of the skin. It is not known if diet can influence skin photoaging. Objectives:
To study the influence of a calorie-restricted diet and an obesity diet in mice
exposed to long-term UV-B irradiation to assess if there is an association
between diet and histopathological response to UV-B irradiation. Design, Setting,
and Participants: In this animal model study in an academic setting, the dorsal
skin of SKH1 hairless mice receiving normal, calorie-restricted, and obesity
diets was exposed to UV-B irradiation 3 times a week for 10 weeks and were
compared with corresponding controls. The mice were placed in the following
groups, with 8 animals in each group: (1) intact control (C) with regular diet
and no UV-B exposure, (2) intact control with UV-B exposure (CR), (3) calorie
restricted diet (CrC), (4) calorie-restricted diet with UV-B exposure (CrR), (5)
obesity diet (OC), and (6) obesity diet with UV-B exposure (OR). The experiment
was conducted during October through December 2013. Tissue processing and
histological analysis were completed in 2016. Main Outcomes and Measures:
Histomorphometric analysis was performed on paraffin-embedded skin sections
stained by histological and immunohistochemical methods for estimation of
epidermal thickness, epidermal proliferating cell nuclear antigen index, collagen
I, elastic fibers, fibroblasts, mast cells, dermal cellularity, and adipose layer
ratio. Changes in wrinkles were noted. Results: Hairless female mice (age range,
6-8 weeks) were obtained. With a normal diet, changes from UV-B irradiation
occurred in epidermal thickness, epidermal proliferating cell nuclear antigen
index, collagen I, elastic fibers, fibroblasts, and mast cells, which were
modestly influenced by an obesity diet. Calorie restriction influenced the skin
in nonirradiated control animals, with higher values for most variables. After UV
B exposure in animals with calorie restriction, epidermal thickness was
increased, but other variables were unaffected. Animals receiving the calorie
restricted diet lost weight when exposed to long-term UV-B irradiation. Wrinkles
were reduced in the calorie-restricted control group and in UV-B-exposed animals
who received the obesity diet. Conclusions and Relevance: Dietary alterations
seem to modify histopathological responses to UV-B exposure in the skin of
hairless mice. Level of Evidence: NA.
PMID- 28418520
TI - Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity
Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta
analysis.
AB - Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are
sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To
estimate the ability of a single hs-cTnT concentration below the limit of
detection (<0.005 ug/L) and a nonischemic electrocardiogram (ECG) to rule out AMI
in adults presenting to the emergency department (ED) with chest pain. Data
Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14
December 2016). Study Selection: Cohort studies involving adults presenting to
the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT
measurements were obtained and AMI outcomes adjudicated during initial
hospitalization. Data Extraction: Investigators of studies provided data on the
number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements
<0.005 ug/L) and the number who had AMI during hospitalization (primary outcome)
or a major adverse cardiac event (MACE) or death within 30 days (secondary
outcomes), by risk classification (low or not low risk). Two independent
epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients
in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%)
low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged
from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7%
(95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%;
pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died.
Limitation: Few studies, variation in timing and methods of reference standard
troponin tests, and heterogeneity of risk and prevalence of AMI across studies.
Conclusion: A single hs-cTnT concentration below the limit of detection in
combination with a nonischemic ECG may successfully rule out AMI in patients
presenting to EDs with possible emergency acute coronary syndrome. Primary
Funding Source: Emergency Care Foundation.
PMID- 28418522
TI - A Young Man With Proptosis Causing Decreased Visual Acuity.
PMID- 28418521
TI - Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration
Protective Factors in Elderly Individuals.
AB - Importance: While amyloid and neurodegeneration are viewed together as Alzheimer
disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern
neurodegeneration may be considerably different. Protection from these ADP
factors may be important for aging without significant ADP. Objective: To
identify the combined and independent protective factors for amyloid and AD
pattern neurodegeneration in a population-based sample and to test the hypothesis
that "exceptional agers" with advanced ages do not have significant ADP because
they have protective factors for amyloid and neurodegeneration. Design, Setting,
and Participants: This cohort study conducted a prospective analysis of 942
elderly individuals (70->=90 years) with magnetic resonance imaging and
Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo
Clinic Study of Aging, a longitudinal population-based study of cognitive aging
in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP
by considering individuals 85 years or older to be without significant evidence
of ADP. Main Outcomes and Measures: We evaluated predictors including
demographics, APOE, intellectual enrichment, midlife risk factors (physical
inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the
total number of late-life cardiac and metabolic conditions. We used multivariate
linear regression models to identify the combined and independent protective
factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the
cohort 85 years of age or older, we computed Cohen d-based effect size
estimations to compare the quantitative strength of each predictor variable in
their contribution with exceptional aging without ADP. Results: The study
participants included 423 (45%) women and the average age of participants was
79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife
dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes,
hypertension, and cardiac and metabolic conditions, but not intellectual
enrichment, were associated with greater AD-pattern neurodegeneration. In the 85
years or older cohort, the Cohen d results showed small to moderate effects
(effect sizes > 0.2) of several variables except job score and midlife
hypertension in predicting exceptional aging without ADP. Conclusions and
Relevance: The protective factors that influence amyloid and AD-pattern
neurodegeneration are different. "Exceptional aging" without ADP may be possible
with a greater number of protective factors across the lifespan but warrants
further investigation.
PMID- 28418523
TI - Neurocognitive Trajectory of Boys Who Received a Hematopoietic Stem Cell
Transplant at an Early Stage of Childhood Cerebral Adrenoleukodystrophy.
AB - Importance: Untreated childhood cerebral adrenoleukodystrophy (cALD) is a fatal
disease associated with progressive cerebral demyelination and rapid, devastating
neurologic decline. The standard of care to enhance long-term survival and
stabilize cerebral disease is a hematopoietic stem cell transplant (HSCT).
Neurologic outcomes are better when HSCT occurs at an earlier stage of cALD, yet
there is limited understanding of the neurocognitive trajectory of patients who
undergo HSCT. Objectives: To characterize neurocognitive outcomes of boys with
cALD and early-stage cerebral disease who were treated with an allogeneic HSCT
and to identify disease- and treatment-related factors associated with long-term
functioning. Design, Setting, and Participants: Baseline and follow-up
neurocognitive test performance was analyzed for all boys with cALD who received
an HSCT at the University of Minnesota between January 1, 1991, and October 20,
2014, and who had a pretransplant magnetic resonance imaging (MRI) severity score
of less than 10 (scale range, 0-34; higher scores indicate greater severity).
Main Outcomes and Measures: Longitudinal neurocognitive test performance in 4
domains (verbal comprehension, perceptual [visual] reasoning, working memory, and
processing speed) were the primary outcome measures. Secondary analysis at the
most recent evaluation also included measures of sustained attention, verbal
memory, visual-motor integration, and fine motor function. Results: Among the 62
boys in this study (mean [SD] age at transplant, 8.37 [2.80] years; range, 4-16
years), there was a significant association of pretransplant MRI severity and
baseline verbal comprehension (r = -0.340; P = .008), perceptual reasoning (r =
0.419; P = .001), and processing speed (r = -0.285; P = .03) scores. Higher
pretransplant MRI severity scores were also associated with a steeper decline in
neurocognitive functioning during the 5-year follow-up period. Twenty-two of 33
patients (67%) with available long-term follow-up neurocognitive testing had
severe impairment in at least 1 neurocognitive domain at the most recent
evaluation. Conclusions and Relevance: Boys with cALD who have greater than
minimal cerebral disease detected on MRI scans at the time of an HSCT are at risk
for severe, persistent neurocognitive deficits. These findings motivate further
exploration of methods of detecting cerebral disease prior to development of
lesions observable on MRI scans, an endeavor that may be facilitated by newborn
screening for adrenoleukodystrophy. These findings may serve a benchmark role in
evaluating the efficacy of novel interventions for cALD.
PMID- 28418525
TI - Asymptomatic Microscopic Hematuria-Rethinking the Diagnostic Algorithm.
PMID- 28418524
TI - Evaluating Testing Strategies for Identifying Youths With HIV Infection and
Linking Youths to Biomedical and Other Prevention Services.
AB - Importance: Most human immunodeficiency virus (HIV)-infected youths are unaware
of their serostatus (approximately 60%) and therefore not linked to HIV medical
or prevention services. The need to identify promising and scalable approaches to
promote uptake of HIV testing among youths at risk is critical. Objective: To
evaluate a multisite HIV testing program designed to encourage localized HIV
testing programs focused on self-identified sexual minority males and to link
youths to appropriate prevention services after receipt of their test results.
Design, Setting, and Participants: Testing strategies were evaluated using an
observational design during a 9-month period (June 1, 2015, through February 28,
2016). Testing strategies were implemented by 12 adolescent medicine HIV primary
care programs and included targeted testing, universal testing, or a combination.
Data were collected from local youth at high risk of HIV infection and,
specifically, sexual minority males of color. Main Outcomes and Measures:
Proportion of sexual minority males and sexual minority males of color tested,
proportion of previously undiagnosed HIV-positive youths identified, and rates of
linkage to prevention services. Results: A total of 3301 youths underwent HIV
testing. Overall, 35 (3.6%) of those who underwent universal testing in primary
care clinical settings, such as emergency departments and community health
centers, were sexual minority males (35 [3.6%] were males of color) compared with
236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted
testing and 693 (37.8%) (503 [27.4%] were males of color) through combination
efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%)
via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%)
through targeted testing. However, when targeted tests were separated from
universal testing results for sites using a combined strategy, the rate of newly
identified HIV-positive cases identified through universal testing decreased to 1
(0.1%). Rates of new HIV-positive cases identified through targeted testing
increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%])
were more likely to link successfully to local HIV prevention services, including
preexposure prophylaxis, compared with those who underwent universal testing (328
[34.1%]). Conclusions and Relevance: The findings suggest that community-based
targeted approaches to HIV testing are more effective than universal screening
for reaching young sexual minority males (especially males of color), identifying
previously undiagnosed HIV-positive youths, and linking HIV-negative youths to
relevant prevention services. Targeted, community-based HIV testing strategies
hold promise as a scalable and effective means to identify high-risk youths who
are unaware of their HIV status.
PMID- 28418526
TI - Empirically Determined Vascular Smooth Muscle Cell Mechano-Adaptation Law.
AB - Cardiovascular disease can alter the mechanical environment of the vascular
system, leading to mechano-adaptive growth and remodeling. Predictive models of
arterial mechano-adaptation could improve patient treatments and outcomes in
cardiovascular disease. Vessel-scale mechano-adaptation includes remodeling of
both the cells and extracellular matrix. Here, we aimed to experimentally measure
and characterize a phenomenological mechano-adaptation law for vascular smooth
muscle cells (VSMCs) within an artery. To do this, we developed a highly
controlled and reproducible system for applying a chronic step-change in strain
to individual VSMCs with in vivo like architecture and tracked the temporal
cellular stress evolution. We found that a simple linear growth law was able to
capture the dynamic stress evolution of VSMCs in response to this mechanical
perturbation. These results provide an initial framework for development of
clinically relevant models of vascular remodeling that include VSMC adaptation.
PMID- 28418527
TI - Initial Public Reporting of Quality at Veterans Affairs vs Non-Veterans Affairs
Hospitals.
PMID- 28418528
TI - Understanding Veteran Wait Times.
PMID- 28418529
TI - Anxiety in 11-Year-Old Children Who Stutter: Findings From a Prospective
Longitudinal Community Sample.
AB - Purpose: To examine if a community sample of 11-year-old children with persistent
stuttering have higher anxiety than children who have recovered from stuttering
and nonstuttering controls. Method: Participants in a community cohort study were
categorized into 3 groups: (a) those with persistent stuttering, (b) those with
recovered stuttering, and (c) nonstuttering controls. Linear regression modeling
compared outcomes on measures of child anxiety and emotional and behavioral
functioning for the 3 groups. Results: Without adjustment for covariates
(unadjusted analyses), the group with persistent stuttering showed significantly
increased anxiety compared with the recovered stuttering group and nonstuttering
controls. The group with persistent stuttering had a higher number of children
with autism spectrum disorder and/or learning difficulties. Once these variables
were included as covariates in subsequent analysis, there was no difference in
anxiety, emotional and behavioral functioning, or temperament among groups.
Conclusion: Although recognized to be associated with stuttering in clinical
samples, anxiety was not higher in school-age children who stutter in a community
cohort. It may be that anxiety develops later or is less marked in community
cohorts compared with clinical samples. We did, however, observe higher anxiety
scores in those children who stuttered and had autism spectrum disorder or
learning difficulties. Implications and recommendations for research are
discussed.
PMID- 28418530
TI - Hiding in Plain Sight-Resurrecting the Power of Inspecting the Patient.
PMID- 28418531
TI - Solutions Not Problems: A New Era in After-Hours Care?
PMID- 28418532
TI - Auditory Environment Across the Life Span of Cochlear Implant Users: Insights
From Data Logging.
AB - Purpose: We describe the natural auditory environment of people with cochlear
implants (CIs), how it changes across the life span, and how it varies between
individuals. Method: We performed a retrospective cross-sectional analysis of
Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from
1,501 people with CIs (ages 0-96 years). They covered over 2.4 million hr of
implant use and indicated how much time the CI users had spent in various
acoustical environments. We investigated exposure to spoken language, noise,
music, and quiet, and analyzed variation between age groups, users, and
countries. Results: CI users spent a substantial part of their daily life in
noisy environments. As a consequence, most speech was presented in background
noise. We found significant differences between age groups for all auditory
scenes. Yet even within the same age group and country, variability between
individuals was substantial. Conclusions: Regardless of their age, people with
CIs face challenging acoustical environments in their daily life. Our results
underline the importance of supporting them with assistive listening technology.
Moreover, we found large differences between individuals' auditory diets that
might contribute to differences in rehabilitation outcomes. Their causes and
effects should be investigated further.
PMID- 28418533
TI - Association of a Chronic Stress Biomarker With Advanced Development of Breast and
Testicular Volume.
PMID- 28418535
TI - Breath analysis using external cavity diode lasers: a review.
AB - Most techniques that are used for diagnosis and therapy of diseases are invasive.
Reliable noninvasive methods are always needed for the comfort of patients. Owing
to its noninvasiveness, ease of use, and easy repeatability, exhaled breath
analysis is a very good candidate for this purpose. Breath analysis can be
performed using different techniques, such as gas chromatography mass
spectrometry (MS), proton transfer reaction-MS, and selected ion flow tube-MS.
However, these devices are bulky and require complicated procedures for sample
collection and preconcentration. Therefore, these are not practical for routine
applications in hospitals. Laser-based techniques with small size, robustness,
low cost, low response time, accuracy, precision, high sensitivity, selectivity,
low detection limit, real-time, and point-of-care detection have a great
potential for routine use in hospitals. In this review paper, the recent advances
in the fields of external cavity lasers and breath analysis for detection of
diseases are presented.
PMID- 28418536
TI - Near-infrared angiography for critical limb ischemia in a diabetic murine model.
AB - Peripheral arterial disease (PAD) is a highly prevalent disease process that
afflicts more than 20% of individuals with diabetes. Progression of PAD in the
setting of diabetes can lead to critical limb ischemia (CLI), which is associated
with increased risk of wounds, gangrene, and limb loss. Prompt noninvasive
evaluation of limbs affected by PAD progression and CLI is currently limited.
Here, we evaluate the utility of a custom-designed multispectral imaging system
for fluorescence-based near-infrared angiography and compare it to the existing
gold standard of laser-scanning Doppler perfusion assessments. Due to its higher
resolution and fluorescence sensitivity, near-infrared angiography demonstrates a
greater capacity to characterize altered dynamic arterial perfusion in a
clinically relevant diabetic murine model for CLI. Furthermore, we demonstrate
that our imaging system can accurately track arterial perfusion recovery over
time following induced ischemia, and reveal unique phenotypic differences in the
setting of diabetes.
PMID- 28418537
TI - Assessment of decellularization of heart bioimplants using a Raman spectroscopy
method.
AB - We report the results of experimental studies on cardiac implants using a Raman
spectroscopy method (RS). Raman spectra characteristics of leaves and walls of
cardiac implants were obtained; the implants were manufactured by protocols of
detergent-enzymatic technique (DET) and biological, detergent-free (BIO)
decellularization, using detergents (group DET) or a detergent-free,
nonproteolytic, actin-disassembling regimen (BIO). There were input optical
coefficients that allowed us to carry out evaluation of the protocols of DET and
BIO decellularization on the basis of the concentrations of glycosaminoglycans,
proteins, amides, and DNA. It was shown that during DET and BIO
decellularization, composition aberrations of proteins and lipids do not occur
and the integrity of the collagenous structures is preserved. It was found that
during the DET decellularization, preservation of glycosaminoglycans is better
than during BIO decellularization.
PMID- 28418534
TI - Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas:
standardization and quantitative comparison with histology.
AB - Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image
contrast in many tumors due to the increased accumulation of protoporphyrin IX
(PpIX), a fluorescent porphyrin that is associated with tumor burden and
proliferation. The value of PpIX-guided resection of malignant gliomas has been
demonstrated in prospective randomized clinical studies in which a twofold
greater extent of resection and improved progression-free survival have been
observed. In low-grade gliomas and at the diffuse infiltrative margins of all
gliomas, PpIX fluorescence is often too weak to be detected with current low
resolution surgical microscopes that are used in operating rooms. However, it has
been demonstrated that high-resolution optical-sectioning microscopes are capable
of detecting the sparse and punctate accumulations of PpIX that are undetectable
via conventional low-power surgical fluorescence microscopes. To standardize the
performance of high-resolution optical-sectioning devices for future clinical
use, we have developed an imaging phantom and methods to ensure that the imaging
of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging
studies with a dual-axis confocal microscope demonstrate that these methods
enable the acquisition of images from unsectioned human brain tissues that
quantitatively and consistently correlate with images of histologically processed
tissue sections.
PMID- 28418538
TI - Changing Mindsets to Enhance Treatment Effectiveness.
PMID- 28418539
TI - Ophthalmic Manifestations of Congenital Zika Syndrome in Colombia and Venezuela.
AB - Importance: The ocular manifestations and sequelae of Zika virus infection are
not well known. Recently, the World Health Organization changed the declaration
of Zika as a public health emergency and designated the viral outbreak and
related microcephaly clusters as a long-term program of work. This change
indicates the urgent need to evaluate and document ophthalmic manifestations in
patients for timely management of this disease. In addition, confirmation whether
the public health problem in Brazil extends to other regions in South America is
needed. Objective: To report the ocular manifestations of congenital Zika
syndrome with microcephaly in Colombia and Venezuela. Design, Setting, and
Participants: This prospective case series included 43 patients from 2 ophthalmic
centers in Colombia and Venezuela who underwent evaluation from October 1, 2015,
through June 30, 2016, and were clinically diagnosed with congenital Zika
syndrome. Twenty patients were Hispanic; 13, African; 8, white; and 2, Native
American. Interventions: Ophthalmic and systemic evaluations and serologic
testing were performed on all infants. Patients underwent external ocular
examination and dilated ophthalmoscopy. Serologic testing ruled out
toxoplasmosis, rubella, cytomegalovirus, syphilis, and human immunodeficiency
virus. Main Outcomes and Measures: Ophthalmic manifestations of congenital Zika
syndrome. Results: Of the 43 patients included in this series (28 female and 15
male), the mean (SD) age at examination was 2.1 (1.5) months. The mothers of all
the children had no ophthalmic findings and did not report ocular symptoms during
pregnancy. All patients had bilateral ophthalmic manifestations. Optic nerve
findings included hypoplasia with the double-ring sign, pallor, and increased cup
disc ratio in 5 patients (11.6%). Macular abnormalities included mild to severe
pigment mottling in 27 patients (63%) and lacunar maculopathy in 3 (6.9%).
Chorioretinal scarring was present in 3 patients (7%). Eleven patients (26%) had
a combination of lesions in the posterior pole. Five patients (12%) were
diagnosed with congenital glaucoma, characterized by the clinical triad of
epiphora, photophobia, and blepharospasm; increased intraocular pressure; corneal
clouding at birth; and buphthalmos. These data reveal that 12% (95% CI, 5%-24%)
of cases of congenital Zika with microcephaly had anterior segment abnormalities
and 88% (95% CI, 76%-94%) had important macular and optic nerve abnormalities.
The visual sequelae of these ophthalmic manifestations remain unknown.
Conclusions and Relevance: Congenital Zika syndrome in the current study had
severe ocular abnormalities, and all patients had bilateral involvement. Ocular
findings were focal macular pigment mottling, chorioretinal atrophy with a
predilection for the macular area, congenital glaucoma and optical nerve
hypoplasia, and optic disc abnormalities. Ophthalmic examination is recommended
in patients with congenital Zika syndrome.
PMID- 28418540
TI - Guideline: ACP and AAFP recommend systolic BP targets based on history and risk
level in adults >= 60 years of age.
PMID- 28418541
TI - Guideline: In type 2 diabetes, ACP recommends metformin monotherapy if drugs are
needed for glycemic control.
PMID- 28418542
TI - Review: Sulfonylureas are associated with overall mortality and CV events vs
other antihyperglycemics in T2DM.
PMID- 28418543
TI - Review: HbA1c has low accuracy for prediabetes; lifestyle programs and metformin
reduce progression to T2DM.
PMID- 28418544
TI - Review: In patients with ureteric lithiasis, alpha-blockers increase stone
expulsion.
PMID- 28418545
TI - Review: In CAD without HF, RAS inhibitors reduce deaths more than placebo but not
active control.
PMID- 28418546
TI - In patients in the emergency department with acute pain, 10, 15, and 30 mg of
ketorolac did not differ for pain relief.
PMID- 28418547
TI - Review: Adding anticholinergics to beta2-agonists for asthma exacerbations
reduces hospitalizations.
PMID- 28418548
TI - Review: Metformin is linked to reduced mortality in type 2 diabetes with comorbid
CKD and CHF.
PMID- 28418549
TI - Glasgow Blatchford score predicted intervention or death better than 4 other
prediction models in upper GI bleeding.
PMID- 28418550
TI - Cost-Effectiveness of Sacubitril-Valsartan in Patients Who Have Heart Failure
With Reduced Ejection Fraction.
PMID- 28418551
TI - Cost-Effectiveness of Sacubitril-Valsartan in Patients Who Have Heart Failure
With Reduced Ejection Fraction.
PMID- 28418552
TI - Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and
Consideration for Organ Donation.
PMID- 28418553
TI - Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and
Consideration for Organ Donation.
PMID- 28418554
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418555
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418556
TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement.
PMID- 28418557
TI - A Strong and Simple Heart.
PMID- 28418558
TI - Lectures on Inhumanity: Teaching Medical Ethics in German Medical Schools Under
Nazism.
AB - Nazi medicine and its atrocities have been explored in depth over the past few
decades, but scholars have started to examine medical ethics under Nazism only in
recent years. Given the medical crimes and immoral conduct of physicians during
the Third Reich, it is often assumed that Nazi medical authorities spurned
ethics. However, in 1939, Germany introduced mandatory lectures on ethics as part
of the medical curriculum. Course catalogs and archival sources show that
lectures on ethics were an integral part of the medical curriculum in Germany
between 1939 and 1945. Nazi officials established lecturer positions for the new
subject area, named Medical Law and Professional Studies, at every medical
school. The appointed lecturers were mostly early members of the Nazi Party and
imparted Nazi political and moral values in their teaching. These values included
the unequal worth of human beings, the moral imperative of preserving a pure
Aryan people, the authoritarian role of the physician, the individual's
obligation to stay healthy, and the priority of public health over individual
patient care. This article shows that there existed not only a Nazi version of
medical ethics but also a systematic teaching of such ethics to students in Nazi
Germany. The findings illustrate that, from a historical point of view, the
notion of "eternal values" that are inherent to the medical profession is
questionable. Rather, the prevailing medical ethos can be strongly determined by
politics and the zeitgeist and therefore has to be repeatedly negotiated.
PMID- 28418559
TI - Web Exclusives. Annals for Hospitalists Inpatient Notes - Human Factors
Engineering and Inpatient Care-New Ways to Solve Old Problems.
PMID- 28418560
TI - Web Exclusives. Annals Consult Guys - Like Pulling Teeth: Antiplatelet Therapy in
the Dental Office.
PMID- 28418563
TI - Tensile Mechanical Properties and Dynamic Collagen Fiber Re-Alignment of the
Murine Cervix are Dramatically Altered Throughout Pregnancy.
AB - The cervix is a unique organ able to dramatically change its shape and function
by serving as a physical barrier for the growing fetus and then undergoing
dramatic dilation allowing for delivery of a term infant. As a result, the cervix
endures changing mechanical forces from the growing fetus. There is an emerging
concept that the cervix may change or remodel "early" in many cases of
spontaneous preterm birth (sPTB). However, the mechanical role of the cervix in
both normal and preterm birth remains unclear. Therefore, the primary objective
of this study was to determine the mechanical and structural responses of murine
cervical tissue throughout a normal gestational time course. In this study, both
tissue structural and material properties were determined via a quasi-static
tensile load-to-failure test, while simultaneously obtaining dynamic collagen
fiber re-alignment via cross-polarization imaging. This study demonstrated that
the majority of the mechanical properties evaluated decreased at midgestation and
not just at term, while collagen fiber re-alignment occurred earlier in the
loading curve for cervices at term. This suggests that although structural
changes in the cervix occur throughout gestation, the differences in material
properties function in combination with collagen fiber re-alignment as mechanical
precursors to regulate term gestation. This work lays a foundation for
investigating cervical biomechanics and the role of the cervix in preterm birth.
PMID- 28418564
TI - Ultra Wide-Field Laser Scanning Imaging of an Unusually Bullous Retinoschisis:
Retinoschisis vs Detachment.
PMID- 28418565
TI - Familial Exudative Vitreoretinopathy.
PMID- 28418566
TI - Peripheral Exudative Hemorrhagic Chorioretinopathy.
PMID- 28418567
TI - Serpiginous Choroiditis.
PMID- 28418571
TI - Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant
Exposure: A Systematic Review and Meta-analysis.
AB - Importance: Several studies have examined the links between prenatal exposure to
antidepressants and autism spectrum disorders (ASDs) in children, with
inconsistent results, especially regarding the impact of the trimester of
exposure. Objective: To perform a systematic review of the literature and a meta
analysis of published studies to assess the association between ASDs and fetal
exposure to antidepressants during pregnancy for each trimester of pregnancy and
preconception. Data Sources: PubMed, EMBASE, and PsycINFO databases up to May
2016 were searched in June 2016 for observational studies. For the meta-analyses,
data were analyzed on RevMan version 5.2 using a random-effect model. For the
review, studies were included if they had been published and were cohort or case
control studies, and for the meta-analysis, studies were included if they were
published studies and the data were not derived from the same cohorts. Study
Selection: We included all the studies that examined the association between ASDs
and antenatal exposure to antidepressants. Data Extraction and Synthesis: Three
reviewers independently screened titles and abstracts, read full-text articles,
and extracted data. The quality of the studies was also assessed. Main Outcomes
and Measures: Primary outcome was the association between antidepressants during
pregnancy and ASDs. Secondary outcomes were the associations between
antidepressants in each individual trimester or before pregnancy and ASDs.
Results: Our literature search identified 10 relevant studies with inconsistent
results. For prenatal exposure, the meta-analysis on the 6 case-control studies
(117 737 patients) evidenced a positive association between antidepressant
exposure and ASDs (odds ratio [OR], 1.81; 95% CI, 1.49-2.20). The association was
weaker when controlled for past maternal mental illness (OR, 1.52; 95% CI, 1.09
2.12). A similar pattern was found whatever the trimester of exposure considered
(first trimester: OR, 2.09, 95% CI,1.66-2.64; second: OR, 2.00, 95% CI, 1.55
2.59; and third: OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental
illness: first trimester: OR, 1.79; 95% CI, 1.27-2.52, second: OR, 1.67, 95% CI,
1.14-2.45; and third: OR, 1.54, 95% CI, 0.82-2.90). No association was found when
the 2 cohort studies were pooled (772 331 patients) for the whole pregnancy
(hazard ratio, 1.26; 95% CI, 0.91-1.74) or for the first trimester. In addition,
preconception exposure to antidepressants was significantly associated with an
increased risk for ASDs (OR controlled for past maternal illness, 1.77; 95% CI,
1.49-2.09). Conclusions and Relevance: There is a significant association between
increased ASD risk and maternal use of antidepressants during pregnancy; however,
it appears to be more consistent during the preconception period than during each
trimester. Maternal psychiatric disorders in treatment before pregnancy rather
than antenatal exposure to antidepressants could have a major role in the risk
for ASDs. Future studies should address the problem of this potential confounder.
PMID- 28418572
TI - The Single High-Sensitivity Serum Cardiac Troponin T Level: A Significant Advance
for Chest Pain Pathways?
PMID- 28418573
TI - Trends in Surgical Management and Costs for Operative Treatment of Proximal
Humerus Fractures in the Elderly.
AB - Proximal humerus fractures in the elderly are increasing in frequency as the
population ages. The purpose of this study was to investigate surgical and cost
trends in the Medicare population. The PearlDiver database was queried using
diagnosis codes to identify Medicare recipients with proximal humerus fractures
from 2005 to 2012. Surgical trends, demographics, and charge/reimbursement data
were analyzed. There were 750,426 proximal humerus fractures in Medicare
recipients during the 8-year period. Eighty-five percent of the fractures were
treated nonoperatively; however, the percentage of operative vs nonoperative
management increased significantly over time for all fractures, isolated
fractures, and fracture dislocations. Open reduction and internal fixation (ORIF)
was the most common surgical treatment and remained constant. Reverse total
shoulder arthroplasty (RTSA) increased by 406% and hemiarthroplasty (HEMI)
decreased by 47%. Compared with younger patients, older patients were more likely
to undergo HEMI or RTSA than to undergo ORIF for isolated fractures and fracture
dislocations. Charges and reimbursements from Medicare increased over time. The
charge to reimbursement gap increased from 87% in 2005 to 104% in 2012. Charges
were higher for RTSA than for ORIF or HEMI. Nonoperative management was the
treatment of choice for 85% of proximal humerus fractures in the elderly;
however, there was a trend toward higher rates of surgery. The RTSA rate
increased and the HEMI rate decreased, while ORIF remained constant. There was an
increasing charge to reimbursement ratio for all procedure types. [Orthopedics.
2017; 40(4):e641-e647.].
PMID- 28418574
TI - Inadequacy of Joint Aspiration for Detection of Persistent Periprosthetic
Infection During Two-Stage Septic Revision Knee Surgery.
AB - Despite the lack of validation, synovial aspiration remains a common practice
during 2-stage septic revision total knee arthroplasty (TKA). The goal of this
study was to investigate the diagnostic validity of synovial
polymethylmethacrylate (PMMA) spacer aspiration of temporary knee arthrodesis to
detect persistent periprosthetic joint infection before TKA reimplantation. This
retrospective cohort study included 73 consecutive patients who underwent 2-stage
septic revision TKA according to a standard protocol. After explantation surgery,
including temporary arthrodesis with an intramedullary stabilized PMMA spacer,
all patients had synovial aspiration 2 weeks before reimplantation to exclude
persistent periprosthetic joint infection. Patients had a 2-week antibiotic
holiday before aspiration. Sensitivity and specificity of the synovial PMMA
spacer joint aspiration for the detection of periprosthetic joint infection were
determined and referenced against intraoperative microbiologic and histologic
samples obtained at second-stage surgery. Sensitivity of the synovial PMMA spacer
aspiration was 21%. Because of poor diagnostic validity, synovial PMMA spacer
aspiration cannot be recommended for routine exclusion of persistent
periprosthetic joint infection before TKA reimplantation. Therefore, exclusion of
persistent periprosthetic joint infection should be supplemented by other
diagnostic methods, and it is not necessary to delay TKA reimplantation for PMMA
spacer aspiration. [Orthopedics. 2017; 40(4):231-234.].
PMID- 28418575
TI - Effects of Previous Osteotomy on Outcome of Hip Resurfacing Arthroplasty.
AB - The effect of previous conservative surgeries on the outcome of metal-on-metal
hip resurfacing arthroplasty (HRA) has not been studied. This study compared
postoperative clinical scores and survivorship results of hips with and without
previous osteotomies in a population of patients who underwent HRA. A total of
1101 patients (1375 hips) with a mean age of 51.3 years at the time of surgery
underwent HRA at a single center. Sixty-nine patients had undergone prior surgery
on the operated hip including 14 osteotomies (1 pelvic, 6 femoral, and 7 combined
pelvic and femoral osteotomies). Mean follow-up was comparable for patients with
prior osteotomy and patients in the control group (101 months vs 96 months,
P=.6916); however, patients with prior osteotomies were much younger at the time
of surgery (34 years vs 51 years, P=.0001). Kaplan-Meier survival estimates were
calculated, and the Cox proportional hazard ratio was used to adjust for the
covariates that differed between the 2 groups and affected the survivorship of
hip resurfacing. Patients who underwent prior osteotomy showed lower pain and
activity scores. In addition, patients who underwent prior osteotomy had a
greater chance of revision than the rest of the cohort (hazard ratio, 3.87; 95%
confidence interval, 1.54-9.68; P=.004). For patients in whom the natural anatomy
or the bone quality of the hip has been severely altered by a prior osteotomy,
HRA may be contraindicated if good component fixation cannot be achieved and hip
biomechanics restored. [Orthopedics. 2017; 40(4):e609-e616.].
PMID- 28418576
TI - The "Safe Zone" Technique Improves Suture Placement and Accuracy During
Arthroscopic Remplissage.
AB - In response to recent concerns about the accuracy of suture passage during
arthroscopic remplissage, this study was conducted to determine whether a
previously described "safe zone" technique can improve the accuracy of suture
passage. A recommended safe zone technique was used for arthroscopic remplissage
on 6 cadaveric specimens. The safe zone was described as a region at least 1 cm
lateral and no greater than 3 cm distal to the posterolateral acromion. Results
were compared with a control group of 6 specimens for which the safe zone
technique was not used. For each group, 24 suture passes were performed. In the
safe zone group, 83.3% (20 of 24) of sutures passed through the infraspinatus
tendon. This was a significant improvement compared with the control group, in
which only 25% (6 of 24) of sutures pierced the infraspinatus tendon (P<.01). In
the safe zone group, 4.2% (1 of 24) of attempted suture passes were placed
through the muscle or musculotendinous junction compared with 75% (18 of 24) in
the control group (P<.01). Prevention of overmedialization improved significantly
with the safe zone technique. In the safe zone group, both anchors had
significantly more lateral (6 to 10 mm) suture passage compared with the control
group (P<.01). The safe zone technique also showed greater precision of suture
passes, and overall precision (SD) improved in 75% of passes. The safe zone
technique significantly improved the accuracy of suture penetration into the
infraspinatus tendon during arthroscopic remplissage. This reproducible method
may help to prevent the reported complications of remplissage. [Orthopedics.
2017; 40(4):e598-e603.].
PMID- 28418577
TI - Prospective Assessment of Sleep Quality Before and After Primary Total Joint
Replacement.
AB - Sleep disruption is a common, yet rarely addressed, complaint among patients who
have undergone total joint arthroplasty (TJA). This study assessed sleep quality
before and after primary TJA. A total of 105 patients who underwent primary total
hip arthroplasty (THA) or total knee arthroplasty (TKA) prospectively completed
questionnaires during the preoperative, early postoperative, and late
postoperative periods. The survey included the Epworth Sleepiness Scale, current
sleeping habits, and patient perspectives of sleep quality and duration. In the
early postoperative period (4.7+/-2.0 weeks), patients reported significant
increases in sleep disturbance as denoted by increased length of time to fall
asleep (P=.006) and mean nightly awakenings (P=.002) compared with the
preoperative baseline. At late postoperative follow-up (40.8+/-19.5 weeks),
patients' sleep quality subsequently improved above the preoperative baseline.
Approximately 40% of patients tried a new sleeping method postoperatively, the
most common being new pillow placement. No significant differences in pre- or
postoperative sleeping trends were noted between THA and TKA patients. These
findings suggest transient sleep disturbance is common in the early postoperative
period, with subsequent improvement by 10-month follow-up after a primary TJA.
Given the growing importance of patient satisfaction in health care systems,
orthopedic surgeons must manage patients' expectations while working with them to
optimize sleep quality after TJA. A multimodal approach with preoperative
counseling, early postoperative sleep modifications, and possibly preemptive use
of medications may improve transient sleep disturbance among TJA patients.
[Orthopedics. 2017; 40(4):e636-e640.].
PMID- 28418579
TI - ?
PMID- 28418578
TI - ?
PMID- 28418580
TI - Effect of surfactant species and electrophoretic medium composition on the
electrophoretic behavior of neutral and water-insoluble linear synthetic polymers
in nonaqueous capillary zone electrophoresis.
AB - We have recently demonstrated the separation of neutral and water-insoluble
linear synthetic polymers in nonaqueous capillary zone electrophoresis (NACZE)
using a cationic surfactant of cetyltrimethylammonium chloride (CTAC). In this
study, eight ionic surfactants were investigated for the separation of four
synthetic polymers (polystyrene, polymethylmethacrylates, polybutadiene, and
polycarbonate); only three surfactants (CTAC, dimethyldioctadecylammonium
bromide, and sodium dodecylsulfate) caused their separation. The order of the
interaction between the polymers and the surfactants depended on both the
surfactant species and the composition of the electrophoretic medium. Their
investigation revealed that the separation is majorly affected by the hydrophobic
interactions between the polymers and the ionic surfactants. In addition, the
electrophoretic behavior of polycarbonate suggested that electrostatic
interaction also affects the selectivity of the polymers.
PMID- 28418581
TI - Leaf rust infection reduces herbivore-induced volatile emission in black poplar
and attracts a generalist herbivore.
AB - Plants release complex volatile blends after separate attack by herbivores and
pathogens, which play many roles in interactions with other organisms. Large
perennials are often attacked by multiple enemies, but the effect of combined
attacks on volatile emission is rarely studied, particularly in trees. We
infested Populus nigra trees with a pathogen, the rust fungus Melampsora larici
populina, and Lymantria dispar caterpillars alone and in combination. We
investigated poplar volatile emission and its regulation, as well as the behavior
of the caterpillars towards volatiles from rust-infected and uninfected trees.
Both the rust fungus and the caterpillars alone induced volatile emission from
poplar trees. However, the herbivore-induced volatile emission was significantly
reduced when trees were under combined attack by the herbivore and the fungus.
Herbivory induced terpene synthase transcripts as well as jasmonate
concentrations, but these increases were suppressed when the tree was
additionally infected with rust. Caterpillars preferred volatiles from rust
infected over uninfected trees. Our results suggest a defense hormone crosstalk
upon combined herbivore-pathogen attack in poplar trees which results in lowered
emission of herbivore-induced volatiles. This influences the preference of
herbivores, and might have other far-reaching consequences for the insect and
pathogen communities in natural poplar forests.
PMID- 28418582
TI - COP1 conveys warm temperature information to hypocotyl thermomorphogenesis.
AB - Plants adjust their architecture to optimize growth and reproductive success
under changing climates. Hypocotyl elongation is a pivotal morphogenic trait that
is profoundly influenced by light and temperature conditions. While hypocotyl
photomorphogenesis has been well characterized at the molecular level, molecular
mechanisms underlying hypocotyl thermomorphogenesis remains elusive. Here, we
demonstrate that the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1)
conveys warm temperature signals to hypocotyl thermomorphogenesis. To investigate
the roles of COP1 and its target ELONGATED HYPOCOTYL 5 (HY5) during hypocotyl
thermomorphogenesis, we employed Arabidopsis mutants that are defective in their
genes. Transgenic plants overexpressing the genes were also produced. We examined
hypocotyl growth and thermoresponsive turnover rate of HY5 protein at warm
temperatures under both light and dark conditions. Elevated temperatures trigger
the nuclear import of COP1, thereby alleviating the suppression of hypocotyl
growth by HY5. While the thermal induction of hypocotyl growth is circadian
gated, the degradation of HY5 by COP1 is uncoupled from light responses and
timing information. We propose that thermal activation of COP1 enables
coincidence between warm temperature signaling and circadian rhythms, which
allows plants to gate hypocotyl thermomorphogenesis at the most profitable time
at warm temperatures.
PMID- 28418583
TI - Lung cancer-A global perspective.
AB - Lung cancer is the leading cause of cancer deaths worldwide. While tobacco
exposure is responsible for the majority of lung cancers, the incidence of lung
cancer in never smokers, especially Asian women, is increasing. There is a global
variation in lung cancer biology with EGFR mutations being more common in Asian
patients, while Kras mutation is more common in Caucasians. This review will
focus on the global variations in lung cancer and its treatment.
PMID- 28418584
TI - Transforming growth factor beta-inhibitor Repsox downregulates collagen
expression of scleroderma dermal fibroblasts and prevents bleomycin-induced mice
skin fibrosis.
AB - Inhibition of transforming growth factor (TGF)-beta1 signalling may be one of the
most reliable approaches to treat skin fibrosis of scleroderma. Although there
have been many basic researches of TGF-beta blockade reagents, few of them were
proved to have inhibitory effects on fibrosis both in vitro and in vivo. In this
study, we randomly chose four commercially available low molecular weight
compounds (Repsox, LY2109761, LY364947 and K02288) from TGF-beta1 inhibitor
library, and compared their antifibrotic effects in vitro and in vivo. We
demonstrated that Repsox has the most potent inhibitory effects on TGF-beta
induced expression of CTGF and collagen of cultured normal dermal fibroblasts in
vitro and their constitutive overexpression of scleroderma fibroblast in vitro.
In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the
downregulation of CTGF or collagen. Our results may facilitate clinical trial of
Repsox against fibrotic diseases in future.
PMID- 28418585
TI - miR-128-1 is not required for hair pigmentation in mice.
AB - MicroRNAs are endogenous, regulatory RNAs implicated in many biological processes
including pigmentation. Software algorithms and in vitro experiments predict that
microRNAs can target pigmentation pathway genes, but few have been tested in
vivo. MiR-128-1, a microRNA within the strongly selected lactase locus in the
human genome, has predicted pigmentation targets. To test the role of miR-128-1
in pigment regulation, we created C57BL/6 agouti miR-128-1 knockout mice and
quantified melanin deposition in hair. MiR-128-1 knockout mice have no detectable
hair pigmentation phenotype. We conclude that miR-128-1 does not play a
significant regulatory role in hair pigmentation in mice.
PMID- 28418586
TI - Simulated presence therapy for dementia.
AB - BACKGROUND: Dementia is a common and serious neuropsychiatric syndrome,
characterised by progressive cognitive and functional decline. The majority of
people with dementia develop behavioural disturbances, also known as behavioural
and psychological symptoms of dementia (BPSD). Several non-pharmacological
interventions have been evaluated to treat BPSD in people with dementia.
Simulated presence therapy (SPT), an intervention that uses video or audiotape
recordings of family members played to the person with dementia, is a possible
approach to treat BPSD. OBJECTIVES: To assess the effects of SPT on behavioural
and psychological symptoms and quality of life in people with dementia. SEARCH
METHODS: We searched ALOIS (the Specialised Register of the Cochrane Dementia and
Cognitive Improvement Group), CENTRAL (The Cochrane Library) (9 February 2016),
MEDLINE Ovid SP (1946 to 6 January 2017), Embase Ovid SP (1972 to 6 January
2017), PsycINFO Ovid SP (1806 to 6 January 2017), CINAHL via EBSCOhost (1980 to 6
January 2017), LILACS via BIREME (all dates to 6 January 2017),
ClinicalTrials.gov (ClinicalTrials.gov) (all dates to 6 January 2017), and the
World Health Organization (WHO) Portal (apps.who.int/trialsearch) (all dates to 6
January 2017). We also checked the reference lists of relevant articles to
identify any additional studies. SELECTION CRITERIA: Randomised and quasi
randomised controlled trials, including cross-over studies, that evaluated the
efficacy of SPT, consisting of personalised audio or videotape recordings of
family members, in people with any form of dementia. DATA COLLECTION AND
ANALYSIS: Two authors independently selected studies, assessed risk of bias and
extracted data. No meta-analyses were conducted because of substantial
heterogeneity among the included studies. MAIN RESULTS: Three trials with 144
participants met the inclusion criteria. Two of the trials had a randomised cross
over design, one was a cross-over trial which we classified as quasi
randomised.Participants in the included studies were people with dementia living
in nursing homes. They were predominantly women and had a mean age of over 80
years. SPT was performed using an audio or video recording prepared by family
members or surrogates. It varied in its content, frequency of administration and
duration. All the studies compared multiple treatments. In one study, SPT was
compared with two other interventions; in the other two studies, it was compared
with three other interventions. Specifically, SPT was compared to usual care,
personalised music (two studies), a 'placebo' audiotape containing the voice of a
person (two studies), and one-to-one social interaction performed by trained
research assistants (one study). In terms of outcomes evaluated, one study
considered agitation and withdrawn behaviour (both assessed with three methods);
the second study evaluated verbal disruptive behaviour (assessed with three
methods); and the third study evaluated physically agitated behaviour and
verbally agitated behaviour (the method used was not clearly described).According
to the GRADE criteria, the overall quality of the evidence was very low due to
very small numbers of participants and risk of bias in the included studies;
(none of the trials was at low risk of selection bias; all the trials were at
high risk of performance bias; one trial was at high risk of attrition bias; and
all had unclear selective reporting).Because of variation in the participants,
the format of SPT, the comparison interventions, and the measures used to assess
outcomes, we judged the results unsuitable for a meta-analysis.Within each trial,
the effect of SPT on behaviour, compared to usual care, was mixed and depended on
the measure used. Two trials which included a personalised music intervention
reported no significant differences between simulated presence and music on
behavioural outcomes. Because the overall quality of the evidence was very low,
we were very uncertain regarding all the resultsNone of the studies evaluated
quality of life or any of our secondary outcome measures (performance of
activities of daily living, dropout and carer burden). AUTHORS' CONCLUSIONS: We
were unable to draw any conclusions about the efficacy of SPT for treating
behavioural and psychological symptoms and improving quality of life of people
with dementia. New high-quality studies are needed to investigate the effect of
SPT.
PMID- 28418587
TI - Short Syntheses of 4-Deoxycarbazomycin B, Sorazolon E, and (+)-Sorazolon E2.
AB - Short syntheses of 4-deoxycarbazomycin B and sorazolon E were established through
the condensation of cyclohexanone and commercially available 4-methoxy-2,3
dimethylaniline, followed by PdII -catalyzed dehydrogenative
aromatization/intramolecular C-C bond coupling and deprotection. A chiral
dinuclear vanadium complex (Ra ,S,S)-6 mediated the enantioselective oxidative
coupling of sorazolon E, affording (+)-sorazolon E2 in good enantioselectivity.
PMID- 28418588
TI - Intracellular ROS levels determine the apoptotic potential of keratinocyte by
Quantum Dot via blockade of AKT Phosphorylation.
AB - Quantum dots (QDs) have shown great potential for biomedical use in a broad range
including diagnostic agents. However, the regulatory mechanism of dermal toxicity
is poorly understood. In this study, we investigated how QDs-induced apoptosis is
regulated in human keratinocytes. We also examined the effect of carboxylic acid
coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and
apoptosis-related cellular signalling. The viability of keratinocyte was
inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS
production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT
dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3
and caspases-9 was significantly increased. We also found that a decrease in
cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the
abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis.
Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and
AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic
potential in the human skin equivalent model (HSEM). These data show that QD
induced intracellular ROS levels may be an important parameter in QD-induced
apoptosis. These findings from this study indicate that intracellular ROS levels
might determine the apoptotic potential of keratinocyte by QD via blockade of AKT
phosphorylation.
PMID- 28418589
TI - A distinct cutaneous microbiota profile in autoimmune bullous disease patients.
AB - Bullous pemphigoid (BP) is the most common autoimmune blistering disease in
Europe. As both the incidence of the disease and the relative proportion of the
elderly population continue to rise, it represents a significant medical burden.
Whereas some progress has been achieved in defining genetic risk factors for
autoimmune blistering diseases, no environmental agent has been conclusively
identified. Emerging evidence suggests that host immunity may influence the skin
microbiota, while the latter modulates cutaneous immunity. Nevertheless, the
relationship between skin microbial communities and autoimmune bullous disease
has yet to be studied in humans. Here, we aim to characterise and compare the
skin microbiome of patients with BP and healthy, age-matched controls at numerous
body sites. Similar to what has been shown in healthy controls, the composition
of skin microbiota in patients with BP appears to be very divergent and site
specific. Microbial phylum abundances differ between perilesional sites of
patients with BP and the same anatomic locations of control patients. A distinct
cutaneous microbiota profile, which correlates with BP, further strengthens the
significance of commensal-host interaction on our immune system. Moreover, these
results raise the possibility that the cutaneous microbiome may contribute to the
pathogenesis of BP, with important implications for the treatment of this
disease.
PMID- 28418590
TI - Control of biofouling by xanthine oxidase on seawater reverse osmosis membranes
from a desalination plant: enzyme production and screening of bacterial isolates
from the full-scale plant.
AB - : Control of biofouling on seawater reverse osmosis (SWRO) membranes is a major
challenge as treatments can be expensive, damage the membrane material and often
biocides do not remove the polymers in which bacteria are embedded. Biological
control has been largely ignored for biofouling control. The objective of this
study was to demonstrate the effectiveness of xanthine oxidase enzyme against
complex fouling communities and then identify naturally occurring bacterial
strains that produce the free radical generating enzyme. Initially, 64 bacterial
strains were isolated from different locations of the Perth Seawater Desalination
Plant. In our preceding study, 25/64 isolates were selected from the culture
collection as models for biofouling studies, based on their prevalence in
comparison to the genomic bacterial community. In this study, screening of these
model strains was performed using a nitroblue tetrazolium assay in the presence
of hypoxanthine as substrate. Enzyme activity was measured by absorbance. Nine of
25 strains tested positive for xanthine oxidase production, of which
Exiguobacterium from sand filters and Microbacterium from RO membranes exhibited
significant levels of enzyme production. Other genera that produced xanthine
oxidase were Marinomonas, Pseudomonas, Bacillus, Pseudoalteromonas and
Staphylococcus. Strain variations were observed between members of the genera
Microbacterium and Bacillus. SIGNIFICANCE AND IMPACT OF THE STUDY: Xanthine
oxidase, an oxidoreductase enzyme that generates reactive oxygen species, is
endogenously produced by many bacterial species. In this study, production of the
enzyme by bacterial isolates from a full-scale desalination plant was
investigated for potential use as biological control of membrane fouling in
seawater desalination. We have previously demonstrated that free radicals
generated by a commercially available xanthine oxidase in the presence of a
hypoxanthine substrate, effectively dispersed biofilm polysaccharides on
industrially fouled membranes. Bacterial xanthine oxidase production in the
presence of hypoxanthine may prove to be a cost effective, in situ method for
alleviation of fouling.
PMID- 28418591
TI - A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused
by SLURP1 deficiency.
AB - Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar
keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully
recapitulates the human disease, with increased keratinocyte proliferation and
thickening of the epidermis on the volar surface of the paws. There has long been
speculation that SLURP1 serves as a ligand for a receptor that regulates
keratinocyte growth and differentiation. We were intrigued that mutations leading
to increased signalling through the epidermal growth factor receptor (EGFR) cause
PPK. Here, we sought to determine whether reducing EGFR signalling would
ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we
bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele.
The hypomorphic Egfr allele, which leads to reduced EGFR signalling in
keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency,
suggesting that SLURP1 deficiency causes PPK independently (or downstream) from
the EGFR pathway.
PMID- 28418592
TI - From the Editors.
PMID- 28418593
TI - Nonparametric Tree-Based Predictive Modeling of Storm Outages on an Electric
Distribution Network.
AB - This article compares two nonparametric tree-based models, quantile regression
forests (QRF) and Bayesian additive regression trees (BART), for predicting storm
outages on an electric distribution network in Connecticut, USA. We evaluated
point estimates and prediction intervals of outage predictions for both models
using high-resolution weather, infrastructure, and land use data for 89 storm
events (including hurricanes, blizzards, and thunderstorms). We found that
spatially BART predicted more accurate point estimates than QRF. However, QRF
produced better prediction intervals for high spatial resolutions (2-km grid
cells and towns), while BART predictions aggregated to coarser resolutions
(divisions and service territory) more effectively. We also found that the
predictive accuracy was dependent on the season (e.g., tree-leaf condition, storm
characteristics), and that the predictions were most accurate for winter storms.
Given the merits of each individual model, we suggest that BART and QRF be
implemented together to show the complete picture of a storm's potential impact
on the electric distribution network, which would allow for a utility to make
better decisions about allocating prestorm resources.
PMID- 28418594
TI - Massive crab recruitment events to the shallow subtidal zone.
PMID- 28418595
TI - Validation of PAGE-B model in Asian chronic hepatitis B patients receiving
entecavir or tenofovir.
AB - BACKGROUND & AIMS: A new hepatocellular carcinoma risk prediction model, PAGE-B,
which includes age, gender and platelet count as constituent variables, has
recently been proposed in Caucasian chronic hepatitis B patients. We validated
PAGE-B model and compared its accuracy with that of conventional risk prediction
models in Asian chronic hepatitis B patients. METHODS: Chronic hepatitis B
patients treated with entecavir or tenofovir were consecutively recruited. The
performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG
HCC and REACH-B) were analysed. RESULTS: A total of 1092 chronic hepatitis B
patients (668 men, 61.2%) were selected between August 2006 and January 2015. The
mean age was 48 years. During the follow-up period (median, 43.6 months), 36
(3.3%) patients developed hepatocellular carcinoma. Older age (hazard ratio
[HR]=1.077), male gender (HR=3.676) and lower platelet count (HR=0.984) were
independent predictors of hepatocellular carcinoma development. The PAGE-B showed
similar area under receiver operating characteristic curves (AUROCs) to GAG-HCC
and CU-HCC at 3 years (0.777 vs 0.793 and 0.743, respectively; all P>.05) and 5
years (0.799 vs 0.803 and 0.744, respectively; all P>.05), whereas the AUROCs of
PAGE-B were significantly higher than those of the REACH-B (0.602 at 3 years and
0.572 at 5 years, P<.05). CONCLUSIONS: Our study demonstrated that PAGE-B is
applicable to Asian chronic hepatitis B patients receiving ETV or TDF therapy.
The PAGE-B showed similar predictive performance to GAG-HCC and CU-HCC.
PMID- 28418596
TI - Hair follicle dermal stem cells and skin-derived precursor cells: Exciting tools
for endogenous and exogenous therapies.
AB - Understanding the cellular interactions and molecular signals underlying hair
follicle (HF) regeneration may have significant implications for restorative
therapies for skin disease that diminish hair growth, whilst also serving to
provide fundamental insight into the mechanisms underlying adult tissue
regeneration. One of the major, yet underappreciated, players in this process is
the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal
progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss
their potential functions within the skin and their relationship to skin-derived
precursors (SKPs), and consider unanswered questions about the function of these
specialized fibroblasts. We contend that dermal stem cells provide an important
reservoir of renewable dermal progenitors that may enable development of novel
restorative therapies following hair loss, skin injury or disease.
PMID- 28418597
TI - Mid-trimester residual cervical length and the risk of preterm birth in
pregnancies after abdominal radical trachelectomy: a retrospective analysis.
AB - OBJECTIVE: To investigate the association between mid-trimester residual cervical
length (CL) and the risk of preterm birth in pregnancies after abdominal radical
trachelectomy (RT). DESIGN: Retrospective cohort study. SETTING: University
hospital. POPULATION: A total of 33 deliveries after 22 weeks' gestation in 30
women who underwent abdominal RT including prophylactic cervical cerclage and
perinatal care between January 2002 and May 2016. METHODS: The association
between mid-trimester residual CL (the distance between the cerclage and the
external cervical os) and gestational age at delivery was investigated. Receiver
operating characteristics (ROC) curve analysis was performed to estimate the
optimal cut-off values of the mid-trimester residual CL for the prediction of
preterm birth. MAIN OUTCOME MEASURES: Preterm birth before 34 weeks' gestation.
RESULTS: Mid-trimester residual CL showed a significant correlation with
gestational age at delivery (r = 0.36, P < 0.05). There was a significant
difference in residual CL between women who did and those who did not give birth
before 34 weeks (P < 0.05). Mid-trimester residual CL < 13 mm was a good
predictor of birth before 34 weeks, with a sensitivity of 67%, specificity of
75%, positive predictive value of 55% and negative predictive value of 86% (area
under ROC curve, 0.75). CONCLUSIONS: Mid-trimester residual CL is significantly
correlated with gestational age at delivery. Residual CL assessment could be used
to reassure physicians and women that there is only a small chance of preterm
birth in pregnancies after abdominal RT. TWEETABLE ABSTRACT: Mid-trimester
residual cervical length is a good predictor of preterm birth after radical
trachelectomy.
PMID- 28418598
TI - Redox-Disproportionation of a Decamethyltitanocene(III) Isonitrile Alkynyl
Complex.
AB - A mixed decamethyltitanocene(III) isonitrile alkynyl complex (7) was synthesized
by the sequential introduction of the isonitrile and alkynyl ligands. Direct
synthesis results in the formation of the diamagnetic decamethyltitanocene
bis(isonitrile) (2) and bis(alkynyl) (3) complexes. Compound 7 undergoes
disproportionation at room temperature to give 2 and 3. All complexes were fully
characterized by IR, NMR, and EPR spectroscopy, and mass spectrometry. Molecular
structures for complexes 2 and 7 are reported. The stability and reactivity of
these complexes are rationalized by DFT computations.
PMID- 28418599
TI - Use of the Harmonic scalpel for Delorme's procedure.
AB - AIM: There are many surgical techniques that deal with external rectal prolapse
but perineal procedures have the advantage of reduced invasiveness. Therefore,
despite concerns regarding high recurrence rates, the technique is still used by
many surgeons. METHOD: This manuscript and video describe our early clinical
experience using the Harmonic scalpel in 11 consecutive patients who underwent a
Delorme's procedure for external rectal prolapse. RESULTS: The median age of
patients was 76 (range: 30-94) years. There were no intra-operative
complications, and the median operative time was 78 min. Intra-operative blood
loss was minimal (mean 45 ml; range 20-70 ml). Median length of stay was 2
(range: 0-8) days. Overall morbidity and recurrence were both 18%, with a median
follow-up of 15 (range: 1-23) months. Nine patients were operated on by a senior
trainee with consultant supervision. CONCLUSION: The advantages of this device
are mainly those of ease of mucosal dissection, minimal blood loss and shorter
operative time in comparison with published series.
PMID- 28418600
TI - Validation of a laboratory-developed test of human sperm capacitation.
AB - Sperm must undergo capacitation to become fertilization competent. Here we
validated that monosialotetrahexosylganglioside (GM1 ) localization patterns,
which were assessed in the Cap-ScoreTM Sperm Function Test, reflect a capacitated
state in human sperm. First, we defined patterns representing sperm that do or do
not respond to stimuli for capacitation. Sperm with "capacitated" patterns had
exposed acrosomal carbohydrates and underwent acrosome exocytosis in response to
calcium ionophore (A23187). Precision was evaluated by percent change of the Cap
Score measured for 50, 100, 150, and 200 sperm. Changes of 11%, 6%, and 5% were
observed (n >= 23); therefore, we counted >=150 sperm per condition. Variance
within and between readers was evaluated using 20 stitched image files generated
from unique ejaculates. Two trained readers randomly resampled each image 20
times, reporting an average standard deviation of 3 Cap-Score units and
coefficient of variation of 13% when rescoring samples, with no difference
between readers. Semen liquefaction times <=2 hr and mechanical liquefaction with
Pasteur or wide-orifice transfer pipettes did not alter Cap-Score values.
However, liquefaction with chymotrypsin (p = 0.002) and bromelain (p = 0.049)
reduced response to capacitating stimuli and induced membrane damage, while
counterintuitively improving sperm motility. Together, these data validate the
Cap-Score assay for the intended purpose of providing information on sperm
capacitation and male fertility. In addition to its clinical utility as a
diagnostic tool, this test of sperm function can reveal the impact of common
practices of semen handling on the ability of sperm to respond to capacitation
stimuli.
PMID- 28418601
TI - Two arginine residues in the COOH-terminal of human beta-defensin-3 constitute an
essential motif for antimicrobial activity and IL-6 production.
AB - Human beta-defensin-3 (HBD-3) possesses antimicrobial activities and the
potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of
two arginine residues (Arg or R) in the COOH-terminal region. To understand the
bioactive properties of the Arg residues of HBD-3, we examined antimicrobial
activities against Staphylococcus aureus and Pseudomonas aeruginosa using
synthetic HBD-2, HBD-3 and two variant peptides of HBD-3: the Arg-truncated
variant designated desR HBD-3 and NRR HBD-3, in which both Arg residues were
shifted to the N-terminal region. IL-6 production from keratinocytes was studied
using the peptides. HBD-3 possessed approximately five-fold more potent
antimicrobial activities, evaluated as the minimum inhibitory concentration
(MIC), against S. aureus compared with desR and NRR HBD-3, while no significant
activity was observed in HBD-2. The antimicrobial activity of HBD-3 against S.
aureus was well preserved even at high sodium chloride concentrations, but was
attenuated in desR and NRR HBD-3. All the peptides exhibited similar
antimicrobial activities against P. aeruginosa, but HBD-2 and desR HBD-3 showed
diminished antimicrobial activities against P. aeruginosa at high salt
concentrations. IL-6 production was significantly induced in keratinocytes with
HBD-3, but not remarkably with stimulation by other peptide. These Arg residues
are essential for the antimicrobial and biological properties of HBD-3.
PMID- 28418602
TI - Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in
psoriasis skin.
AB - Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane
receptors with key functions in canonical Wnt signalling. Wnt ligands are thought
to play an important role in innate immunity and psoriasis, and recent studies
assigned LRP5/6 anti-inflammatory properties. The objective of this study was to
investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in
peripheral blood and in mononuclear cells of patients with chronic plaque type
psoriasis compared with control individuals. To investigate the effect of UV-B
radiation, LRP5/6 skin gene expression was analysed before and after narrowband
UV-B treatment. Our results showed significantly decreased gene expression of
LRP5 and LRP6 in lesional skin and in peripheral blood from patients with
psoriasis compared with non-lesional skin and healthy control skin.
Immunohistochemistry did not reveal differences in protein expression of LRP5/6.
Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene
expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin
and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in
psoriasis.
PMID- 28418603
TI - Towards Quantitative Systems Pharmacology Models of Chemotherapy-Induced
Neutropenia.
AB - Neutropenia is a serious toxic complication of chemotherapeutic treatment. For
years, mathematical models have been developed to better predict hematological
outcomes during chemotherapy in both the traditional pharmaceutical sciences and
mathematical biology disciplines. An increasing number of quantitative systems
pharmacology (QSP) models that combine systems approaches, physiology, and
pharmacokinetics/pharmacodynamics have been successfully developed. Here, I
detail the shift towards QSP efforts, emphasizing the importance of incorporating
systems-level physiological considerations in pharmacometrics.
PMID- 28418605
TI - The G534E variant in HABP2 is not associated with increased risk of familial
nonmedullary thyroid cancer in Brazilian Kindreds.
PMID- 28418604
TI - Loss of INK4a/Arf gene enhances ultraviolet radiation-induced cutaneous tumor
development.
AB - The CDKN2A locus encodes for tumor suppressor genes p16INK4a and p14Arf which are
frequently inactivated in human skin tumors. The purpose of this study was to
determine the relationship between loss of INK4a/Arf activity and inflammation in
the development of ultraviolet (UV) radiation-induced skin tumors. Panels of
INK4a/Arf-/- mice and wild-type (WT) mice were treated with a single dose of UVB
(200 mJ/cm2 ). For long-term studies, these mice were irradiated with UVB (200
mJ/cm2 ) three times weekly for 30 weeks. At the end of the experiment, tissues
were harvested from mice and assayed for inflammatory biomarkers and cytokines. A
single dose of UVB resulted in a significant increase in reactive oxygen species
(ROS) and 8-dihydroxyguanosine (8-oxo-dG) lesions in INK4a/Arf-/- mice compared
to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf-/-
mice had tumors, whereas there were no tumors in WT controls after 24 weeks of
UVB exposure. The increase in tumor development correlated with a significant
increase in nuclear factor (NF)-kappaB, cyclooxygenase-2 (COX-2), prostaglandin
E2 (PGE2 ) and its receptors both in UVB-exposed skin and in the tumors. A
significant increase was seen in inflammatory cytokines in skin samples of
INK4a/Arf-/- mice following treatment with chronic UVB radiation. Furthermore,
significantly more CD11b+ Gr1+ myeloid cells were present in UVB-exposed
INK4a/Arf-/- mice compared to WT mice. Our data indicate that by targeting UVB
induced inflammation, it may be possible to prevent UVB-induced skin tumors in
individuals that carry CDKN2A mutation.
PMID- 28418606
TI - Nationwide incidence of blindness in South Korea: a 12-year study from 2002 to
2013.
AB - IMPORTANCE: Blindness is an important public health issue. BACKGROUND: The
background of the study is to determine the incidence of blindness in South
Korea. DESIGN: Nationwide population-based retrospective study. PARTICIPANTS: All
individuals from South Korea (n = 47 516 098). METHODS: Patients confirmed with
legal blindness based on the worse-seeing and better-seeing eyes between 1
January 2002 and 31 December 2013 were included. The Korean National Health
Insurance Service (KNHIS) database was used. Using the World Health Organization
definition, blindness was defined as best-corrected visual acuity in the worse
seeing and better-seeing eyes of <20/400. The mean incidence of blindness during
the 12-year period was estimated. The population of South Korea was estimated
using census data in 2005 and 2010. MAIN OUTCOME MEASURES: The total number of
legal blindness cases in the KNHIS database. RESULTS: We identified 195 004 and
20 492 cases of newly developed legal blindness based on the worse-seeing and
better-seeing eyes, respectively, and the mean incidences of blindness were 34.2
and 3.6 cases/100 000 person-years, respectively. The prevalence of blindness
based on the worse-seeing and better-seeing eyes was 425.3 and 57.7 cases/100 000
persons, respectively. The incidence of blindness based on the worse-seeing eye
was higher in men than in women overall. Additionally, the incidence increased
with age and showed a decreasing trend from 2002 to 2013. CONCLUSIONS AND
RELEVANCE: The prevalence of blindness showed an increasing trend from 2002 to
2013. The findings of our study will help in the assessment of the blindness
related socio-economic burden and in healthcare planning.
PMID- 28418607
TI - Current trends in quantitative proteomics - an update.
AB - Proteins can provide insights into biological processes at the functional level,
so they are very promising biomarker candidates. The quantification of proteins
in biological samples has been routinely used for the diagnosis of diseases and
monitoring the treatment. Although large-scale protein quantification in complex
samples is still a challenging task, a great amount of effort has been made to
advance the technologies that enable quantitative proteomics. Seven years ago, in
2009, we wrote an article about the current trends in quantitative proteomics. In
writing this current paper, we realized that, today, we have an even wider
selection of potential tools for quantitative proteomics. These tools include new
derivatization reagents, novel sampling formats, new types of analyzers and
scanning techniques, and recently developed software to assist in assay
development and data analysis. In this review article, we will discuss these
innovative methods, and their current and potential applications in proteomics.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28418608
TI - Methods for the isolation and 3D culture of dermal papilla cells from human hair
follicles.
AB - The dermal papilla is a cluster of mesenchymal cells located at the base of the
hair follicle which have a number of important roles in the regulation of hair
growth. As a consequence, in vitro models of these cells are widely used to study
the molecular mechanisms which underlie hair follicle induction, growth and
maintenance. While dermal papilla from rodent hair follicles can be digested
prior to cell isolation, the unique extracellular matrix composition found in
human dermal papilla renders enzymes such as trypsin and collagenase insufficient
for digestion of the dermal papilla into a single cell suspension. As such, to
grow human dermal papilla cells in vitro, the papilla has to first be isolated
via a micro-dissection approach from the follicle. In this article we describe
the micro-dissection and culture methods, which we use within our laboratory, for
the study of human dermal papilla cells.
PMID- 28418609
TI - Real-time measurement of needle forces and acute pressure changes during
intravitreal injections.
AB - BACKGROUND: The purpose of this study was to use a physiological pressure
transducer to measure real-time, continuous pressure changes in an ex vivo study
model of porcine eyes to record the amount of force needed for scleral
penetration and to measure acute intraocular pressure rise during intravitreal
injections. METHODS: A pressure transducer was inserted into the anterior chamber
of 30 fresh porcine eyes, and intraocular pressure was measured 2 s prior to
intravitreal injection until 2 s after. A force transducer plate was used to
insert various gauge needles into the vitreous cavity and the amount of force in
Newtons (N) required for scleral penetration was recorded. RESULTS: For scleral
perforation, 32- and 30-gauge needles required 0.44 N and 0.45 N, significantly
less than larger gauge needles (P < 0.05). Similarly, 27- and 25-gauge needles
required more force than smaller gauge needles but less than 19 gauge (P < 0.05).
Intraocular pressure increased an average of 64.5 mmHg during intravitreal
injection. Two seconds postinjection intraocular pressure readings showed a
residual intraocular pressure increase of 11.1 mmHg from pre-injection baseline.
CONCLUSION: Real-time continuous recordings of pressure reveal that an
instantaneous intraocular pressure spike occurs during intravitreal injection and
appears to be separate from the intraocular pressure spike that occurs during
needle insertion. This pressure spike is transient and has not been captured by
previous methods of intraocular pressure measurement, which rely on single time
point measurements. The clinical significance of this brief intraocular pressure
spike is unclear and warrants further investigation.
PMID- 28418610
TI - Localization patterns of the ganglioside GM1 in human sperm are indicative of
male fertility and independent of traditional semen measures.
AB - Semen analysis lacks a functional component and best identifies extreme cases of
infertility. The ganglioside GM1 is known to have functional roles during
capacitation and acrosome exocytosis. Here, we assessed whether GM1 localization
patterns (Cap-ScoreTM) correspond with male fertility in different settings:
Study 1 involved couples pursuing assisted reproduction in a tertiary care
fertility clinic, while Study 2 involved men with known fertility versus those
questioning their fertility at a local urology center. In Study 1, we examined
various thresholds versus clinical history for 42 patients; 13 had Cap-Scores
>=39.5%, with 12 of these (92.3%) achieving clinical pregnancy by natural
conception or <=3 intrauterine insemination cycles. Of the 29 patients scoring
<39.5%, only six (20.7%) attained clinical pregnancy by natural conception or <=3
intrauterine insemination cycles. In Study 2, Cap-Scores were obtained from 76
fertile men (Cohort 1, pregnant partner or recent father) and compared to 122 men
seeking fertility assessment (Cohort 2). Cap-Score values were normally
distributed in Cohort 1, with 13.2% having Cap-Scores more than one standard
deviation below the mean (35.3 +/- 7.7%). Significantly, more men in Cohort 2 had
Cap-Scores greater than one standard deviation below the normal mean (33.6%; p =
0.001). Minimal/no relationship was found between Cap-Score and sperm
concentration, morphology, or motility. Together, these data demonstrate that Cap
Score provides novel, clinically relevant insights into sperm function and male
fertility that complement traditional semen analysis. Furthermore, the data
provide normal reference ranges for fertile men that can help clinicians counsel
couples toward the most appropriate fertility treatment.
PMID- 28418611
TI - Ectopic expression of the transcription factor MafB in basal keratinocytes
induces hyperproliferation and perturbs epidermal homeostasis.
AB - Mammalian epidermis is composed of four morphologically and functionally distinct
layers of keratinocytes. The innermost basal layer consists of proliferating self
renewing keratinocytes, which also undergo asymmetric cell division to
differentiate into postmitotic suprabasal cells throughout life. Control of the
balance between growth and differentiation of basal cells is important for
epidermal homeostasis to prevent skin disorders including malignancies; however,
the underlying mechanism remains to be elucidated. Recently, MafB was identified
as one of the transcription factors that regulate epidermal keratinocyte
differentiation. MafB is expressed in postmitotic differentiating keratinocytes,
and epidermal differentiation is partially impaired in MafB-deficient mice. To
further establish the roles of MafB in the epidermis in vivo, we generated mice
transgenic for MafB under the control of the basal cell-specific keratin (Krt) 14
promoter. In the epidermis of transgenic mice at embryonic day 18.5, the number
of proliferating Krt14-positive basal-like cells was increased, and the granular
and cornified layers were thickened. Furthermore, these MafB transgenic mice
developed papillomas spontaneously with age. Therefore, MafB promotes
differentiation in postmitotic keratinocytes and simultaneously has potential to
promote growth when ectopically expressed in undifferentiated basal
keratinocytes.
PMID- 28418612
TI - An efficient and enantioselective Michael addition of aromatic oximes to
alpha,beta-unsaturated aldehydes promoted by a chiral diamine catalyst derived
from alpha,alpha-diphenyl prolinol.
AB - Chiral diamine catalysts 11a-e derived from alpha,alpha-diphenyl prolinol were
prepared and successfully applied to the Michael addition of aromatic oximes to
alpha,beta-unsaturated aldehydes in mediocre to good yields (up to 78%) and good
to high enantioselectivities (up to 93% ee).
PMID- 28418613
TI - Complement-independent blistering mechanisms in bullous pemphigoid.
AB - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that
clinically demonstrates tense blisters with widespread erythema, histologically
demonstrates subepidermal blistering and immunologically demonstrates the
presence of circulating autoantibodies against hemidesmosomal molecules.
Complement activation has long been regarded as necessary for the generation of
the BP. However, certain evidence has recently come to support non-complemental
blistering mechanisms. The story of BP blistering mechanisms is a complicated
one. This review mainly focuses on a specific blistering mechanism that
highlights the role of complements in BP blistering.
PMID- 28418614
TI - Efficacy and safety of low-dose heparin in hemodialysis.
AB - INTRODUCTION: The dose of unfractionated heparin (UFH) administered during
hemodialysis (HD) varies widely. This prospective study evaluated the safety and
efficacy of UFH dose de-escalation. METHODS: Sixty-six prevalent patients on HD
receiving UFH per standard-dose protocol (load dose [LD] 50-75 units/kg,
maintenance dose [MD] 500-1000 units/hour) had heparin prescription converted to
low-dose protocol (start LD 15 units/kg and MD 500 units/hour; dose adjusted in
small increments based on assessments of extracorporeal blood circuit).
Coagulation parameters, dialysis adequacy, dialyzer clotting, anemia management,
and dialyzer reuse rates were compared based on the heparin protocol. FINDINGS:
Mean(SD) UFH dose per HD session, before and after protocol conversion, was
6178(2644) and 2913(1116) units, respectively (P < 0.0001). This corresponded to
LD 52.1(16.6) units/kg and MD 615(207) units/hour with standard-dose protocol,
and LD 18.3(6.5) units/kg and MD 505(27) units/hour with low-dose protocol (P <
0.0001). Mid and postdialysis aPTT was 55.3(31.2) and 35.1(7.8) seconds before,
and 37.3(12.9) and 31.5(5.3) seconds after conversion (P = 0.007 and 0.003,
respectively); no significant changes in D-dimer levels occurred. Low-dose UFH
was associated with a small increase in URR and spKt/V (73.0 and 1.54) compared
with dialysis clearance on standard-dose UFH (71.2 and 1.48, respectively, P =
0.02). Weekly dose of ESA decreased by 2388 units postconversion (P = 0.03),
while hemoglobin levels and the weekly dose of intravenous iron did not change (P
= 0.16 and 0.78). A small rise in the rate of moderate dialyzer clotting at the
end of HD was noted with low-dose UFH (5.7% vs. 7.5%, P = 0.002); the rate of
severe dialyzer clotting events did not change (P = 0.91). No change in the
dialyzer reuse rate was noted (18.5 vs. 17.0 treatments, P = 0.26). DISCUSSION:
Low-dose heparinization did not compromise dialysis adequacy and permitted ESA
dose reduction. Our findings suggest that in prevalent patients on HD, UFH dose
of 15-20 units/kg loading and 500 units/hour maintenance was medically safe and
effective.
PMID- 28418616
TI - Communicating the health effects of indoor exposure to particulate matter.
PMID- 28418615
TI - Co-expression of GR79 EPSPS and GAT yields herbicide-resistant cotton with low
glyphosate residues.
AB - Glyphosate-resistant (GR) crops have been adopted on a massive scale by North and
South American farmers. Currently, about 80% of the 120 million hectares of the
global genetically modified (GM) crops are GR crop varieties. However, the
adoption of GR plants in China has not occurred at the same pace, owing to
several factors including, among other things, labour markets and the residual
effects of glyphosate in transgenic plants. Here, we report the co-expression of
codon-optimized forms of GR79 EPSPS and N-acetyltransferase (GAT) genes in
cotton. We found five times more resistance to glyphosate with 10-fold reduction
in glyphosate residues in two pGR79 EPSPS-pGAT co-expression cotton lines, GGCO2
and GGCO5. The GGCO2 line was used in a hybridization programme to develop new GR
cottons. Field trials at five locations during three growing seasons showed that
pGR79-pGAT transgenic cotton lines have the same agronomic performance as
conventional varieties, but were USD 390-495 cheaper to produce per hectare
because of the high cost of conventional weed management practices. Our strategy
to pyramid these genes clearly worked and thus offers attractive promise for the
engineering and breeding of highly resistant low-glyphosate-residue cotton
varieties.
PMID- 28418617
TI - Improved survival of patients with hepatocellular carcinoma and compensated
hepatitis C virus-related cirrhosis who attained sustained virological response.
AB - BACKGROUND: Few studies examined the outcome of patients with hepatitis C virus
(HCV)-related cirrhosis who developed hepatocellular carcinoma (HCC). The
relative weight as determinant of death for cancer vs end-stage liver disease
(ESLD) and the benefit of HCV eradication remain undefined. This multicentre,
retrospective analysis evaluates overall survival (OS), rate of decompensation
and tumour recurrence in compensated HCC patients treated with interferon (IFN)
according to HCV status since HCC diagnosis. METHODS: Two groups of patients with
HCV-related cirrhosis and HCC were followed since HCC diagnosis: (i) compensated
cirrhotics with prior sustained virological response (SVR) on IFN-based regimens
(N=19); (ii) compensated cirrhotics without SVR (viraemic) (N=156). RESULTS: Over
a median follow-up of 3.0 years since the onset of HCC, OS was longer for HCC
patients with SVR than for viraemic patients (log-rank P=.004). The 5-year OS
rate was 65.9% in patients with SVR vs 31.9% in viraemic patients. Similar trends
were reported for hepatic decompensation (log-rank P=.01) and tumour recurrence
(log-rank P=.01). These findings were confirmed at multivariable and propensity
score analysis. At propensity analysis, 0/19 compensated patients with SVR died
for ESLD vs 7/19 (37%) viraemic patients (P=.004). HCC mortality was similar in
the two groups. CONCLUSIONS: Hepatocellular carcinoma patients with prior SVR and
compensated cirrhosis at the time of tumour diagnosis have prolonged OS than
viraemic patients. Given the lack of cirrhosis progression, no SVR patient
ultimately died for ESLD while this condition appears the main cause of death
among viraemic patients.
PMID- 28418619
TI - Determination of lipoic acid in human urine by capillary zone electrophoresis.
AB - Fast, simple, and accurate CE method enabling determination of lipoic acid (LA)
in human urine has been developed and validated. LA is a disulfide-containing
natural compound absorbed from the organism's diet. Due to powerful antioxidant
activity, LA has been used for prevention and treatment of various diseases and
disorders, e.g. cardiovascular diseases, neurodegenerative disorders, and cancer.
The proposed analytical procedure consists of liquid-liquid sample extraction,
reduction of LA with tris(2-carboxyethyl)phosphine, derivatization with 1-benzyl
2-chloropyridinium bromide (BCPB) followed by field amplified sample injection
stacking, capillary zone electrophoresis separation, and ultraviolet-absorbance
detection of LA-BCPB derivative at 322 nm. Effective baseline electrophoretic
separation was achieved within 6 min under the separation voltage of 20 kV (~80
MUA) using a standard fused-silica capillary (effective length 51.5 cm, 75 MUm
id) and BGE consisted of 0.05 mol/L borate buffer adjusted to pH 9. The
experimentally determined limit of detection for LA in urine was 1.2 MUmol/L. The
calibration curve obtained for LA in urine showed linearity in the range 2.5-80
MUmol/L, with R2 0.9998. The relative standard deviation of the points of the
calibration curve was lower than 10%. The analytical procedure was successfully
applied to analysis of real urine samples from seven healthy volunteers who
received single 100 mg dose of LA.
PMID- 28418618
TI - Investigation of Arsenotrophic Microbiome in Arsenic-Affected Bangladesh
Groundwater.
AB - Arsenotrophic bacteria contribute to the nutrient cycling in arsenic (As)
affected groundwater. This study employed a culture-independent and -dependent
investigation of arsenotrophic microbiomes in As affected groundwater samples
collected from Madhabpur, Sonatengra, and Union Porishod in Singair Upazila,
Manikganj, Bangladesh. Total As contents, detected by Atomic Absorption
Spectrophotometry (AAS) of the samples, were 47 ug/L (Madhabpur, SNGW-1), 53 ug/L
(Sonatengra, SNGW-2), and 12 ug/L (Union porishod, SNGW-3), whereas the control
well (SNGW-4; depths >150 m) showed As content of 6 ug/L. Denaturing Gradient Gel
Electrophoresis (DGGE) analysis of the amplified 16S rRNA gene from As-affected
groundwater samples revealed the dominance of aerobic bacteria Pseudomonas within
heterogeneous bacterial populations. DGGE of heterotrophic enrichments
supplemented with arsenite [As (III)] for 4 weeks showed the dominance of
Chryseobacterium, Flavobacterium, and Aquabacterium, whereas the dominant genera
in that of autotrophic enrichments were Aeromonas, Acinetobacter, and
Pseudomonas. Cultured bacteria retrieved from both autotrophic and heterotrophic
enrichments were distinguished into nine genotypes belonging to Chryseobacterium,
Acinetobacter, Escherichia, Pseudomonas, Stenotrophomonas, Janibacter,
Staphylococcus, and Bacillus. They exhibited varying range of As(III) tolerance
from 4 to 27 mM. As(III) transformation potential was confirmed within the
isolates with oxidation rate as high as 0.143 mM/h for Pseudomonas sp. Sn 28. The
arsenotrophic microbiome specifies their potential role in groundwater As-cycling
and their genetic information provide the scientific basis for As-bioremediation.
PMID- 28418621
TI - Issue Information-Declaration of Helsinki.
PMID- 28418620
TI - Fast and Highly Sensitive Ionic-Polymer-Gated WS2 -Graphene Photodetectors.
AB - The combination of graphene with semiconductor materials in heterostructure
photodetectors enables amplified detection of femtowatt light signals using
micrometer-scale electronic devices. Presently, long-lived charge traps limit the
speed of such detectors, and impractical strategies, e.g., the use of large gate
voltage pulses, have been employed to achieve bandwidths suitable for
applications such as video-frame-rate imaging. Here, atomically thin graphene-WS2
heterostructure photodetectors encapsulated in an ionic polymer are reported,
which are uniquely able to operate at bandwidths up to 1.5 kHz whilst maintaining
internal gain as large as 106 . Highly mobile ions and the nanometer-scale Debye
length of the ionic polymer are used to screen charge traps and tune the Fermi
level of the graphene over an unprecedented range at the interface with WS2 .
Responsivity R = 106 A W-1 and detectivity D* = 3.8 * 1011 Jones are observed,
approaching that of single-photon counters. The combination of both high
responsivity and fast response times makes these photodetectors suitable for
video-frame-rate imaging applications.
PMID- 28418622
TI - Newborn Length of Stay and Risk of Readmission.
AB - BACKGROUND: Evidence on the association between newborn length of hospital stay
(LOS) and risk of readmission is conflicting. We compared methods for modelling
this relationship, by gestational age, using population-level hospital data on
births in England between 2005-14. METHODS: The association between LOS and
unplanned readmission within 30 days of postnatal discharge was explored using
four approaches: (i) modelling hospital-level LOS and readmission rates; (ii)
comparing trends over time in LOS and readmission; (iii) modelling individual LOS
and adjusted risk of readmission; and (iv) instrumental variable analyses
(hospital-level mean LOS and number of births on the same day). RESULTS: Of 4 667
827 babies, 5.2% were readmitted within 30 days. Aggregated data showed hospitals
with longer mean LOS were not associated with lower readmission rates for vaginal
(adjusted risk ratio (aRR) 0.87, 95% confidence interval (CI) 0.66, 1.13), or
caesarean (aRR 0.89, 95% CI 0.72, 1.12) births. LOS fell by an average 2.0% per
year for vaginal births and 3.4% for caesarean births, while readmission rates
increased by 4.4 and 5.1% per year respectively. Approaches (iii) and (iv)
indicated that longer LOS was associated with a reduced risk of readmission, but
only for late preterm, vaginal births (34-36 completed weeks' gestation).
CONCLUSIONS: Longer newborn LOS may benefit late preterm babies, possibly due to
increased medical or psychosocial support for those at greater risk of
potentially preventable readmissions after birth. Research based on observational
data to evaluate relationships between LOS and readmission should use methods to
reduce the impact of unmeasured confounding.
PMID- 28418623
TI - An efficient method for gene knock-down by RNA interference in human skin mast
cells.
AB - Mast cells (MCs) from human skin have been notoriously resistant to gene
manipulation, and a method to knock-down gene expression in in situ
differentiated MCs is highly desired. The Dharmacon Accell(r) transfection system
proved successful on several "difficult-to-transfect" cells. In the present work,
we therefore tested this method on skin-derived MCs using different siRNA
entities. The siRNA was readily taken up, followed by pronounced, specific
reduction of gene and protein expression. Hence, we present the first efficient
technique for the manipulation of gene expression in primary skin MCs ex vivo,
which combines high transfection rates with retained cell viability.
PMID- 28418624
TI - Nickel-Cornered Molecular Rectangles as Polycyclic Aromatic Hydrocarbon
Receptors.
AB - Two nickel-cornered organometallic metalla-rectangles containing a pyrene-linked
di-N-heterocyclic carbene have been prepared. The dimensions of one side of the
rectangle were modulated by either using pyrazine or 4,4'-bipyridine. The two
molecules were tested as hosts for the recognition of seven small polycyclic
aromatic hydrocarbons (PAHs) in [D6 ]acetone. By using 1 H NMR spectroscopy
titrations, it could be established that the host-guest stoichiometries of the
inclusion complexes formed were 1:1 for the pyrazine-based host, and 1:2 for the
host containing bipyridine, in accordance with the larger dimensions of the
latter. The molecular structure of the inclusion complex consisting of the
bipyridine-containing host and pyrene was determined by X-ray crystallography,
which confirms the 1:2 host-guest stoichiometry of this species. The
determination of the association constants indicate that the binding strengths
are in the order:
Perylene= C10 is required to maintain the base-pairing
discrimination of thymidine between G and A. The results from our molecular
dynamics simulations show that in the T:G-pair-containing duplex, the geranyl and
farnesyl groups fit into the minor groove and stabilize the overall duplex
stability. This effect cannot be achieved by the shorter carbon chains such as
methyl and dimethylallyl groups. For a duplex containing a T:A pair, the terpene
groups disrupt both hydrogen bonding and stacking interactions by pushing the
opposite A out of the helical structure. Overall, as the terpene chain length
increases, the xT:G pair stabilizes the duplex, whereas the xT:A pair causes
destabilization, indicating the evolutionary significance of the long terpene
group on base-pairing specificity and codon recognition.
PMID- 28418650
TI - Zinc Ion Coordinated Poly(Ionic Liquid) Antimicrobial Membranes for Wound
Healing.
AB - Herein, a series of quaternary ammonium (Qa) or imidazolium (Im) cation-based
poly(ionic liquid) (PIL) membranes and their corresponding zinc ion coordinated
PIL membranes were synthesized. The effects of chemical structure, including
organic cations, alkyl side chain of substitution, and zinc atoms on the
antimicrobial activities against Escherichia coli, Staphylococcus aureus, and
Candida albicans were investigated. The Zn-containing PIL membranes show higher
antibacterial activities compared to those of pristine PIL membranes due to the
synergistic attributes of both organic cations (Qa or Im) and zinc atoms. A wound
healing test using methicillin-resistant S. aureus infected mouse as the model
further demonstrated that zinc ion coordinated PIL membranes were antibacterially
active, biologically safe, and may have potential application as an antimicrobial
wound dressing in a clinical setting.
PMID- 28418651
TI - Electrodeposition of Highly Porous Pt Nanoparticles Studied by Quantitative 3D
Electron Tomography: Influence of Growth Mechanisms and Potential Cycling on the
Active Surface Area.
AB - Nanoporous Pt nanoparticles (NPs) are promising fuel cell catalysts due to their
large surface area and increased electrocatalytic activity toward the oxygen
reduction reaction (ORR). Herein, we report on the influence of the growth
mechanisms on the surface properties of electrodeposited Pt dendritic NPs with
large surface areas. The electrochemically active surface was studied by hydrogen
underpotential deposition (H UPD) and compared for the first time to high-angle
annular dark field scanning transmission electron microscopy (HAADF-STEM)
quantitative 3D electron tomography of individual nanoparticles. Large nucleation
overpotential leads to a large surface coverage of roughened spheroids, which
provide a large roughness factor (Rf) but low mass-specific electrochemically
active surface area (EASA). Lowering the nucleation overpotential leads to highly
porous Pt NPs with pores stretching to the center of the structure. At the
expense of smaller Rf, the obtained EASA values of these structures are in the
range of those of large surface area supported fuel cell catalysts. The active
surface area of the Pt dendritic NPs was measured by electron tomography, and it
was found that the potential cycling in the H adsorption/desorption and Pt
oxidation/reduction region, which is generally performed to determine the EASA,
leads to a significant reduction of that surface area due to a partial collapse
of their dendritic and porous morphology. Interestingly, the extrapolation of the
microscopic tomography results in macroscopic electrochemical parameters
indicates that the surface properties measured by H UPD are comparable to the
values measured on individual NPs by electron tomography after the degradation
caused by the H UPD measurement. These results highlight that the combination of
electrochemical and quantitative 3D surface analysis techniques is essential to
provide insights into the surface properties, the electrochemical stability, and,
hence, the applicability of these materials. Moreover, it indicates that care
must be taken with widely used electrochemical methods of surface area
determination, especially in the case of large surface area and possibly unstable
nanostructures, since the measured surface can be strongly affected by the
measurement itself.
PMID- 28418653
TI - Synthesis and Biological Evaluation of the First Triple Inhibitors of Human
Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA
Phosphodiesterase 2 (Tdp2).
AB - Tdp1 and Tdp2 are two tyrosyl-DNA phosphodiesterases that can repair damaged DNA
resulting from topoisomerase inhibitors and a variety of other DNA-damaging
agents. Both Tdp1 and Tdp2 inhibition could hypothetically potentiate the
cytotoxicities of topoisomerase inhibitors. This study reports the successful
structure-based design and synthesis of new 7-azaindenoisoquinolines that act as
triple inhibitors of Top1, Tdp1, and Tdp2. Enzyme inhibitory data and
cytotoxicity data from human cancer cell cultures establish that modification of
the lactam side chain of the 7-azaindenoisoquinolines can modulate their
inhibitory potencies and selectivities vs Top1, Tdp1, and Tdp2. Molecular
modeling of selected target compounds bound to Top1, Tdp1, and Tdp2 was used to
design the inhibitors and facilitate the structure-activity relationship
analysis. The monitoring of DNA damage by gamma-H2AX foci formation in human
PBMCs (lymphocytes) and acute lymphoblastic leukemia CCRF-CEM cells documented
significantly more DNA damage in the cancer cells vs normal cells.
PMID- 28418652
TI - Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown
Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV
Variants.
AB - Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1
protease inhibitors are reported. Inhibitor 5 displayed superior antiviral
activity and drug-resistance profiles. In fact, this inhibitor showed several
orders of magnitude improved antiviral activity over the FDA approved drug
darunavir. This inhibitor incorporates an unprecedented 6-5-5 ring-fused crown
like tetrahydropyranofuran as the P2 ligand and an aminobenzothiazole as the P2'
ligand with the (R)-hydroxyethylsulfonamide isostere. The crown-like P2 ligand
for this inhibitor has been synthesized efficiently in an optically active form
using a chiral Diels-Alder catalyst providing a key intermediate in high
enantiomeric purity. Two high resolution X-ray structures of inhibitor-bound HIV
1 protease revealed extensive interactions with the backbone atoms of HIV-1
protease and provided molecular insight into the binding properties of these new
inhibitors.
PMID- 28418654
TI - A Robust and Accurate Tight-Binding Quantum Chemical Method for Structures,
Vibrational Frequencies, and Noncovalent Interactions of Large Molecular Systems
Parametrized for All spd-Block Elements (Z = 1-86).
AB - We propose a novel, special purpose semiempirical tight binding (TB) method for
the calculation of structures, vibrational frequencies, and noncovalent
interactions of large molecular systems with 1000 or more atoms. The functional
form of the method is related to the self-consistent density functional TB scheme
and mostly avoids element-pair-specific parameters. The parametrization covers
all spd-block elements and the lanthanides up to Z = 86 using reference data at
the hybrid density functional theory level. Key features of the Hamiltonian are
the use of partially polarized Gaussian-type orbitals, a double-zeta orbital
basis for hydrogen, atomic-shell charges, diagonal third-order charge
fluctuations, coordination number-dependent energy levels, a noncovalent halogen
bond potential, and the well-established D3 dispersion correction. The accuracy
of the method, called Geometry, Frequency, Noncovalent, eXtended TB (GFN-xTB), is
extensively benchmarked for various systems in comparison with existing
semiempirical approaches, and the method is applied to a few representative
structural problems in chemistry.
PMID- 28418655
TI - Accuracy Test of the OPLS-AA Force Field for Calculating Free Energies of Mixing
and Comparison with PAC-MAC.
AB - We have calculated the excess free energy of mixing of 1053 binary mixtures with
the OPLS-AA force field using two different methods: thermodynamic integration
(TI) of molecular dynamics simulations and the Pair Configuration to Molecular
Activity Coefficient (PAC-MAC) method. PAC-MAC is a force field based quasi
chemical method for predicting miscibility properties of various binary mixtures.
The TI calculations yield a root mean squared error (RMSE) compared to
experimental data of 0.132 kBT (0.37 kJ/mol). PAC-MAC shows a RMSE of 0.151 kBT
with a calculation speed being potentially 1.0 * 104 times greater than TI. OPLS
AA force field parameters are optimized using PAC-MAC based on vapor-liquid
equilibrium data, instead of enthalpies of vaporization or densities. The RMSE of
PAC-MAC is reduced to 0.099 kBT by optimizing 50 force field parameters. The
resulting OPLS-PM force field has a comparable accuracy as the OPLS-AA force
field in the calculation of mixing free energies using TI.
PMID- 28418656
TI - Informing the Selection of Screening Hit Series with in Silico Absorption,
Distribution, Metabolism, Excretion, and Toxicity Profiles.
AB - High-throughput screening (HTS) has enabled millions of compounds to be assessed
for biological activity, but challenges remain in the prioritization of hit
series. While biological, absorption, distribution, metabolism, excretion, and
toxicity (ADMET), purity, and structural data are routinely used to select
chemical matter for further follow-up, the scarcity of historical ADMET data for
screening hits limits our understanding of early hit compounds. Herein, we
describe a process that utilizes a battery of in-house quantitative structure
activity relationship (QSAR) models to generate in silico ADMET profiles for hit
series to enable more complete characterizations of HTS chemical matter. These
profiles allow teams to quickly assess hit series for desirable ADMET properties
or suspected liabilities that may require significant optimization. Accordingly,
these in silico data can direct ADMET experimentation and profoundly impact the
progression of hit series. Several prospective examples are presented to
substantiate the value of this approach.
PMID- 28418657
TI - Oil-in-Water Emulsions Stabilized by Saponified Epoxidized Soybean Oil-Grafted
Hydroxyethyl Cellulose.
AB - An oil-in-water emulsion stabilized by saponified epoxidized soybean oil-grafted
hydroxyethyl cellulose (H-ESO-HEC) was investigated. By using an ultrasonic
method, oil-in-water emulsions were prepared by blending 50 wt % soybean oil and
50 wt % H-ESO-HEC aqueous suspensions. The influence of H-ESO-HEC concentrations
on the properties of oil-in-water emulsions was examined. The H-ESO-HEC
concentrations in the aqueous phase varied from 0.02 to 0.40 wt %. When the H-ESO
HEC concentration was 0.4 wt %, the emulsion remained stable for >80 days. The
mean droplet sizes of the emulsions decreased by increasing the H-ESO-HEC
concentration and extending the ultrasonic time. The adsorption amounts of H-ESO
HEC at the oil-water interface increased when the H-ESO-HEC concentrations in the
aqueous phase increased. The rheological property revealed that the apparent
viscosity of the H-ESO-HEC-stabilized oil-in-water emulsions increased when the H
ESO-HEC concentrations increased. Steady flow curves indicated an interfacial
film formation in the emulsions. The evolution of G', G", and tan eta indicated
the predominantly elastic behaviors of all the emulsions.
PMID- 28418658
TI - Cp*Rh(III)/Bicyclic Olefin Cocatalyzed C-H Bond Amidation by Intramolecular Amide
Transfer.
AB - A bicyclic olefin was discovered as a cocatalyst in a Cp*Rh(III)-catalyzed C-H
bond amidation proceeding by an intramolecular amide transfer in N
phenoxyacetamide derivatives. Combining experimental and theoretical studies, we
propose that the olefin promotes a Rh(III) intermediate to undergo oxidative
addition into the O-N bond to form a Rh(V) nitrenoid species and subsequently
direct the nitrenoid to add to the ortho position. The amide directing group
plays a dual role as a cleavable coordinating moiety as well as an essential
coupling partner for the C-H amidation. This methodology was successfully applied
to the late-stage diversification of natural products and a marketed drug under
mild conditions.
PMID- 28418659
TI - Microbial Cell Factories for the Production of Terpenoid Flavor and Fragrance
Compounds.
AB - Terpenoid flavor and fragrance compounds are of high interest to the aroma
industry. Microbial production offers an alternative sustainable access to the
desired terpenoids independent of natural sources. Genetically engineered
microorganisms can be used to synthesize terpenoids from cheap and renewable
resources. Due to its modular architecture, terpenoid biosynthesis is especially
well suited for the microbial cell factory concept: a platform host engineered
for a high flux toward the central C5 prenyl diphosphate precursors enables the
production of a broad range of target terpenoids just by varying the pathway
modules converting the C5 intermediates to the product of interest. In this
review typical terpenoid flavor and fragrance compounds marketed or under
development by biotech and aroma companies are given, and the specificities of
the aroma market are discussed. The main part of this work focuses on key
strategies and recent advances to engineer microbes to become efficient terpenoid
producers.
PMID- 28418660
TI - PEGylated Solanesol for Oral Delivery of Coenzyme Q10.
AB - Coenzyme Q10 (CoQ10) is widely used in preventive or curative treatment of
cardiovascular diseases. However, CoQ10 exhibits an extremely low solubility in
aqueous medium as well as a poor oral bioavailability. Therefore, solanesyl
poly(ethylene glycol) succinate (SPGS) and CoQ10 were formulated as CoQ10-SPGS
micelles with a high content of CoQ10 to improve the bioavailability of CoQ10 in
rat. Findings indicate that, in the CoQ10-SPGS micelles, SPGS is self-assembled
into stable nanosized micelles with a CoQ10 loading capacity of more than 39%.
The CoQ10-SPGS micelles exhibit an enhanced photostability upon exposure to
simulated sunlight. In vivo experiments demonstrate that, as compared to that of
the coarse suspensions of CoQ10, there was three-fold enhancement of oral
bioavailability for CoQ10-loaded SPGS micelles depending on varying molecular
weight of SPGS. In the encapsulation of CoQ10 by SPGS micelles, the self
assembled nanocarriers with strong muco-adhesive properties lead to increases in
the solubility and oral absorption of lipophilic CoQ10 nanoparticles.
PMID- 28418662
TI - Partial in Situ Reduction of Copper(II) Resulting in One-Pot Formation of 2D
Neutral and 3D Cationic Copper(I) Iodide-Pyrazine Coordination Polymers:
Structure and Emissive Properties.
AB - On the way to copper(I) iodide coordination polymers with specific luminescent
properties, the in situ reduction of Cu(II) in the presence of KI and bidentate N
heteroatomic ligand, either pyrazine (pyz) or 4,4'-bipyridine (bpy), resulted in
one two-dimensional and two three-dimensional new coordination networks. Starting
from Cu(NO3)2.3H2O in the presence of pyz, successive precipitation of known
yellow [(CuII)2(pyz)]n, new orange [CuII(pyz)]n, and new dark blue
{[CuI(pyz)2].I5}n polymeric solids was observed. Starting from the same salt in
the presence of bpy resulted in the successive precipitation of known yellow
[(CuII)2(bpy)]n and new brown {[CuII(NO3)(bpy)2].I3.(dmf.H2O)}n coordination
polymers. By using either Cu(CH3COO)2.H2O or Cu(BF4)2 as starting materials, both
known forms, yellow [(CuII)2(bpy)]n and orange [CuII(bpy)]n, precipitated
successively. The new solids were characterized by IR spectroscopy and X-ray
analysis. [CuII(pyz)]n represents the missing member in the row of two
dimensional coordination networks with general formula [CuIX(pyz)]n (X = Cl, Br,
I). Its steady state and time-resolved characterization together with DFT and
TDDFT calculations revealed that the emission at room temperature is mainly
delayed fluorescence originating from mixed singlet metal-to-ligand charge
transfer and halide-to-ligand charge transfer states, while that at 77 K is
phosphorescence, associated with the small singlet-triplet energy differences
(DeltaE = 70 meV).
PMID- 28418661
TI - Systematic Dissociation Pathway Searches Guided by Principal Component Modes.
AB - We introduce a novel method, Pathway Search guided by Internal Motions (PSIM),
that efficiently finds molecular dissociation pathways of a ligand-receptor
system with guidance from principal component (PC) modes obtained from molecular
dynamics (MD) simulations. Modeling ligand-receptor dissociation pathways can
provide insights into molecular recognition and has practical applications,
including understanding kinetic mechanisms and barriers to binding/unbinding as
well as design of drugs with desired kinetic properties. PSIM uses PC modes in
multilayer internal coordinates to identify natural molecular motions that guide
the search for conformational switches and unbinding pathways. The new multilayer
internal coordinates overcome problems with Cartesian and classical internal
coordinates that fail to smoothly present dihedral rotation or generate
nonphysical distortions. We used HIV-1 protease, which has large-scale flap
motions, as an example protein to demonstrate use of the multilayer internal
coordinates. We provide examples of algorithms and implementation of PSIM with
alanine dipeptide and chemical host-guest systems, 2-naphthyl ethanol-beta
cyclodextrin and tetramethylammonium-cryptophane complexes. Tetramethylammonium
cryptophane has slow binding/unbinding kinetics. Its residence time, the length
to dissociate tetramethylammonium from the host, is ~14 s from experiments, and
PSIM revealed 4 dissociation pathways in approximately 150 CPU h. We also
searched the releasing pathways for the product glyceraldehyde-3-phosphate from
tryptophan synthase, and one complete dissociation pathway was constructed after
running multiple search iterations in approximately 300 CPU h. With guidance by
internal PC modes from MD simulations, the PSIM method has advantages over
simulation-based methods to search for dissociation pathways of molecular systems
with slow noncovalent kinetic behavior.
PMID- 28418663
TI - Airborne Quantification of Methane Emissions over the Four Corners Region.
AB - Methane (CH4) is a potent greenhouse gas and the primary component of natural
gas. The San Juan Basin (SJB) is one of the largest coal-bed methane producing
regions in North America and, including gas production from conventional and
shale sources, contributed ~2% of U.S. natural gas production in 2015. In this
work, we quantify the CH4 flux from the SJB using continuous atmospheric sampling
from aircraft collected during the TOPDOWN2015 field campaign in April 2015.
Using five independent days of measurements and the aircraft-based mass balance
method, we calculate an average CH4 flux of 0.54 +/- 0.20 Tg yr-1 (1sigma), in
close agreement with the previous space-based estimate made for 2003-2009. These
results agree within error with the U.S. EPA gridded inventory for 2012. These
flights combined with the previous satellite study suggest CH4 emissions have not
changed. While there have been significant declines in natural gas production
between measurements, recent increases in oil production in the SJB may explain
why emission of CH4 has not declined. Airborne quantification of outcrops where
seepage occurs are consistent with ground-based studies that indicate these
geological sources are a small fraction of the basin total (0.02-0.12 Tg yr-1)
and cannot explain basinwide consistent emissions from 2003 to 2015.
PMID- 28418664
TI - Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation:
Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5
Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide.
AB - We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5
yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus
hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further
characterization in vivo, compound 1 demonstrated an unacceptable level of brain
penetration. In an effort to reduce the level of brain penetration while
maintaining the overall profile, SAR was developed at the C2' position for a
series of close analogues by employing hydrogen bond donors. As a result, 5-[5
phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide (25) was
identified as the lead compound in this series. Compound 25 showed robust effects
in rabbit and canine pharmacodynamic models and an acceptable cross-species
pharmacokinetic profile and was advanced as the clinical candidate. Further
optimization of 25 to mitigate pH-dependent absorption resulted in identification
of the corresponding phosphoramide prodrug (29) with an improved solubility and
pharmacokinetic profile.
PMID- 28418665
TI - Long, Atomically Precise Donor-Acceptor Cove-Edge Nanoribbons as Electron
Acceptors.
AB - This Communication describes a new molecular design for the efficient synthesis
of donor-acceptor, cove-edge graphene nanoribbons and their properties in solar
cells. These nanoribbons are long (~5 nm), atomically precise, and soluble. The
design is based on the fusion of electron deficient perylene diimide oligomers
with an electron rich alkoxy pyrene subunit. This strategy of alternating
electron rich and electron poor units facilitates a visible light fusion reaction
in >95% yield, whereas the cove-edge nature of these nanoribbons results in a
high degree of twisting along the long axis. The rigidity of the backbone yields
a sharp longest wavelength absorption edge. These nanoribbons are exceptional
electron acceptors, and organic photovoltaics fabricated with the ribbons show
efficiencies of ~8% without optimization.
PMID- 28418666
TI - Helical Nanoribbons for Ultra-Narrowband Photodetectors.
AB - This Communication describes a new molecular design that yields ultranarrowband
organic photodetectors. The design is based on a series of helically twisted
molecular ribbons as the optoelectronic material. We fabricate charge collection
narrowing photodetectors based on four different helical ribbons that differ in
the wavelength of their response. The photodetectors made from these materials
have narrow spectral response with full-width at half maxima of <20 nm. The
devices reported here are superior by approximately a factor of 5 to those from
traditional organic materials due to the narrowness of their response. Moreover,
the active layers for the helical ribbon-based photodetectors are solution-cast
but have performance that is comparable to the state-of-the-art narrowband
photodetectors made from methylammonium lead trihalide perovskite single
crystals. The ultranarrow bandwidth for detection results from the helical
ribbons' high absorption coefficient, good electron mobility, and sharp
absorption edges that are defined by the twisted molecular conformation.
PMID- 28418667
TI - Colloid-Facilitated Plutonium Transport in Fractured Tuffaceous Rock.
AB - Colloids have the potential to enhance the mobility of strongly sorbing
radionuclide contaminants in groundwater at underground nuclear test sites. This
study presents an experimental and numerical investigation of colloid-facilitated
plutonium transport in fractured porous media to identify plutonium reactive
transport processes. The transport parameters for dispersion, diffusion,
sorption, and filtration are estimated with inverse modeling by minimizing the
least-squares objective function of multicomponent concentration data from
multiple transport experiments with the shuffled complex evolution metropolis
algorithm. Capitalizing on an unplanned experimental artifact that led to colloid
formation, we adopt a stepwise strategy to first interpret the data from each
experiment separately and then to incorporate multiple experiments simultaneously
to identify a suite of plutonium-colloid transport processes. Nonequilibrium or
kinetic attachment and detachment of plutonium-colloid in fractures were clearly
demonstrated and captured in the inverted modeling parameters along with
estimates of the source plutonium fraction that formed plutonium-colloids. The
results from this study provide valuable insights for understanding the transport
mechanisms and environmental impacts of plutonium in groundwater aquifers.
PMID- 28418668
TI - Computing the Diamagnetic Susceptibility and Diamagnetic Anisotropy of Membrane
Proteins from Structural Subunits.
AB - The behavior of large, complex molecules in the presence of magnetic fields is
experimentally challenging to measure and computationally intensive to predict.
This work proposes a novel, mixed-methods approach for efficiently computing the
principal magnetic susceptibilities and diamagnetic anisotropy of membrane
proteins. The hierarchical primary (amino acid), secondary (alpha helical and
beta sheet), and tertiary (alpha helix and beta barrel) structure of
transmembrane proteins enables analysis of a complex molecule using discrete
subunits of varying size and resolution. The proposed method converts the
magnetic susceptibility tensor for all protein subunits to a unit coordinate
system and sums them to build the magnetic susceptibility tensor for the membrane
protein. Using this approach, we calculate the diamagnetic anisotropy for all
transmembrane proteins of known structure and investigate the effect of different
subunit resolutions on the resulting predictions of diamagnetic anisotropy. We
demonstrate that amino acid residues with aromatic side groups exhibit higher
diamagnetic anisotropies. On average, high percentages of aromatic amino acid
subunits, a beta barrel tertiary structure, and a small volume are correlated
with high volumetric diamagnetic anisotropy. Finally, we demonstrate that
accounting for the spatial position of the residues with respect to one another
is critical to accurately computing the magnetic properties of the complex
protein molecule.
PMID- 28418670
TI - Polarization Effects on the Cellulose Dissolution in Ionic Liquids: Molecular
Dynamics Simulations with Polarization Model and Integrated Tempering Enhanced
Sampling Method.
AB - Conformation of cellulose with various degree of polymerization of n = 1-12 in
ionic liquid 1,3-dimethylimidazolium chloride ([C1mim]Cl) and the intermolecular
interaction between them was studied by means of molecular dynamics (MD)
simulations with fixed-charge and charge variable polarizable force fields,
respectively. The integrated tempering enhanced sampling method was also employed
in the simulations in order to improve the sampling efficiency. Cellulose
undergoes significant conformational changes from a gaseous right-hand helical
twist along the long axis to a flexible conformation in ionic liquid. The
intermolecular interactions between cellulose and ionic liquid were studied by
both infrared spectrum measurements and theoretical simulations. Designated by
their puckering parameters, the pyranose rings of cellulose oligomers are mainly
arranged in a chair conformation. With the increase in the degree of
polymerization of cellulose, the boat and skew-boat conformations of cellulose
appear in the MD simulations, especially in the simulations with polarization
model. The number and population of hydrogen bonds between the cellulose and the
chloride anions show that chloride anion is prone to form HBs whenever it
approaches the hydroxyl groups of cellulose and, thus, each hydroxyl group is
fully hydrogen bonded to the chloride anion. MD simulations with polarization
model presented more abundant conformations than that with nonpolarization model.
The application of the enhanced sampling method further enlarged the
conformational spaces that could be visited by facilitating the system escaping
from the local minima. It was found that the electrostatics interactions between
the cellulose and ionic liquid contribute more to the total interaction energies
than the van der Waals interactions. Although the interaction energy between the
cellulose and anion is about 2.9 times that between the cellulose and cation, the
role of cation is non-negligible. In contrast, the interaction energy between the
cellulose and water is too weak to dissolve cellulose in water.
PMID- 28418671
TI - Area- and Thickness-Dependent Biexciton Auger Recombination in Colloidal CdSe
Nanoplatelets: Breaking the "Universal Volume Scaling Law".
AB - Colloidal nanoplatelets (NPLs) have shown great potentials for lasing
applications due to their sharp absorption and emission peaks, large absorption
cross sections, large radiative decay rates, and long multiexciton lifetimes. How
multiexciton lifetimes depend on material dimensions remains unknown in two
dimensional (2D) materials, despite being a key parameter affecting optical gain
threshold and many other properties. Herein, we report a study of room
temperature biexciton Auger recombination time of CdSe NPLs as a function of
thickness and lateral area. Comparison of all NPLs shows that the biexciton
lifetime does not increase linearly with volume, unlike previously reported
"universal volume scaling law" for quantum dots. For NPLs of the same thickness
(~1.8 nm), the biexciton lifetime increase linearly with their lateral area (from
143.7 +/- 12.6 to 320.1 +/- 17.1 ps when the area increases from 90.5 +/- 21.4 to
234.2 +/- 41.9 nm2). The biexciton lifetime depends linearly on (1/Ek(e))7/2
(Ek(e) is the electron confinement energy) or nearly linearly on d7 (d is NPL
thickness). The observed dependence is consistent with a model in which biexciton
Auger recombination rate scales with the product of exciton binary collision
frequency and Auger recombination probability in biexciton complexes. The linear
increase of Auger lifetimes with NPL lateral areas reflects a 1/area dependence
of the binary collision frequency for 2D excitons and the thickness-dependent
biexciton Auger recombination time is attributed to its strong dependence on the
degree of quantum confinement. This model may be generally applicable to exciton
Auger recombination in quantum confined 1D and 2D nanomaterials.
PMID- 28418673
TI - Aberration-Corrected Electron Beam Lithography at the One Nanometer Length Scale.
AB - Patterning materials efficiently at the smallest length scales is a longstanding
challenge in nanotechnology. Electron-beam lithography (EBL) is the primary
method for patterning arbitrary features, but EBL has not reliably provided sub-4
nm patterns. The few competing techniques that have achieved this resolution are
orders of magnitude slower than EBL. In this work, we employed an aberration
corrected scanning transmission electron microscope for lithography to achieve
unprecedented resolution. Here we show aberration-corrected EBL at the one
nanometer length scale using poly(methyl methacrylate) (PMMA) and have produced
both the smallest isolated feature in any conventional resist (1.7 +/- 0.5 nm)
and the highest density patterns in PMMA (10.7 nm pitch for negative-tone and
17.5 nm pitch for positive-tone PMMA). We also demonstrate pattern transfer from
the resist to semiconductor and metallic materials at the sub-5 nm scale. These
results indicate that polymer-based nanofabrication can achieve feature sizes
comparable to the Kuhn length of PMMA and ten times smaller than its radius of
gyration. Use of aberration-corrected EBL will increase the resolution, speed,
and complexity in nanomaterial fabrication.
PMID- 28418672
TI - A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform
for Triple-Negative Breast Cancer.
AB - Ruthenium coordination complexes have the potential to serve as novel theranostic
agents for cancer. However, a major limitation in their clinical implementation
is effective tumor accumulation. In this study, we have developed a liposome
based theranostic nanodelivery system for [Ru(phen)2dppz](ClO4)2 (Lipo-Ru). This
ruthenium polypyridine complex emits a strong fluorescent signal when
incorporated in the hydrophobic lipid bilayer of the delivery vehicle or in the
DNA helix, enabling visualization of the therapeutic agent in tumor tissues.
Incubation of MDA-MB-231 breast cancer cells with Lipo-Ru induced double-strand
DNA breaks and triggers apoptosis. In a mouse model of triple-negative breast
cancer, treatment with Lipo-Ru dramatically reduced tumor growth. Biodistribution
studies of Lipo-Ru revealed that more than 20% of the injected dose accumulated
in the tumor. These results suggest that Lipo-Ru could serve as a promising
theranostic platform for cancer.
PMID- 28418674
TI - Reversing Enantioselectivity Using Noncovalent Interactions in Asymmetric
Dearomatization of beta-Naphthols: The Power of 3,3' Substituents in Chiral
Phosphoric Acid Catalysts.
AB - The sense of enantioselectivity in asymmetric dearomative amination of beta
naphthols is reported to pivotally depend on the 3,3' substituents on the chiral
BINOL-phosphoric acid (CPA) catalysts. The origin of reversal in the sense of
stereoinduction from R to S, when the aryl substituent is changed from 3,5-(CF3)2
C6H3 (CPA-1) to 9-anthryl (CPA-2), has been identified as arising due to the
change in the pattern of noncovalent interactions (from predominantly C-H...F to
C-H...pi interactions) in the stereocontrolling transition states.
PMID- 28418675
TI - Electric-Field Induced Reversible Switching of the Magnetic Easy Axis in
Co/BiFeO3 on SrTiO3.
AB - Electric-field (E-field) control of magnetism enabled by multiferroic materials
has the potential to revolutionize the landscape of present memory devices
plagued with high energy dissipation. To date, this E-field controlled
multiferroic scheme has only been demonstrated at room temperature using BiFeO3
films grown on DyScO3, a unique and expensive substrate, which gives rise to a
particular ferroelectric domain pattern in BiFeO3. Here, we demonstrate
reversible electric-field-induced switching of the magnetic state of the Co layer
in Co/BiFeO3 (BFO) (001) thin film heterostructures fabricated on (001) SrTiO3
(STO) substrates. The angular dependence of the coercivity and the remanent
magnetization of the Co layer indicates that its easy axis reversibly switches
back and forth 45 degrees between the (100) and the (110) crystallographic
directions of STO as a result of alternating application of positive and negative
voltage pulses between the patterned top Co electrode layer and the (001) SrRuO3
(SRO) layer on which the ferroelectric BFO is epitaxially grown. The coercivity
(HC) of the Co layer exhibits a hysteretic behavior between two states as a
function of voltage. A mechanism based on the intrinsic magnetoelectric coupling
in multiferroic BFO involving projection of antiferromagnetic G-type domains is
used to explain the observation. We have also measured the exact canting angle of
the G-type domain in strained BFO films for the first time using neutron
diffraction. These results suggest a pathway to integrating BFO-based devices on
Si wafers for implementing low power consumption and nonvolatile
magnetoelectronic devices.
PMID- 28418676
TI - Palladium(0)-Catalyzed Dearomative [3 + 2] Cycloaddition of 3-Nitroindoles with
Vinylcyclopropanes: An Entry to Stereodefined 2,3-Fused Cyclopentannulated
Indoline Derivatives.
AB - The palladium(0)-catalyzed diastereoselective dearomative cyclopentannulation of
3-nitroindoles with vinylcyclopropanes is described. This straightforward and
highly atom-economical method leads to a wide range of functionalized indolines
in good yields and diastereoselectivities and represents an unprecedented entry
toward the valuable 2,3-fused cyclopentannulated indoline scaffold.
PMID- 28418677
TI - pH Dependence of Ferricytochrome c Conformational Transitions during Binding to
Cardiolipin Membranes: Evidence for Histidine as the Distal Ligand at Neutral pH.
AB - The conformational changes of ferricytochrome c upon binding to cardiolipin
containing small unilamellar vesicles were studied at slightly acidic pH using
fluorescence, visible circular dichroism, UV-visible absorption, and resonance
Raman spectroscopy. The obtained spectroscopic response data suggest a mode of
interaction, which is clearly distinct from the binding process observed at
neutral pH. Evidence of a reversible and electrostatic binding mechanism under
these conditions is provided through binding inhibition in the presence of 150 mM
NaCl. Moreover, UV-visible absorption and resonance Raman spectra reveal that the
conformational ensemble of membrane bound cytochrome c is dominated by a mixture
of conformers with pentacoordinated and hexacoordinated high-spin heme irons,
which contrast with the dominance of low-spin species at neutral pH. While our
results confirm the L-site binding proposed by Kawai et al., they point to the
protonation of a histidine ligand (H33) as conformational trigger.
PMID- 28418678
TI - Radially Ejected Bubbles Driven by Thermocapillarity in Equilibrated Vapor-Liquid
Mixtures.
AB - We report a novel nucleation method that exploits thermocapillary forces in
binary fluids to generate a cloud of bubbles ejected radially from a thermally
pulsed wire. The bubbles are nucleated within milliseconds of the extinction of
the microsecond pulse and are ejected outward from the wire surface due to the
thermocapillary force created by the radial temperature gradient. At low
temperatures the surface tension of the vapor-liquid mixture, consisting of
ethane-n-octane, increases with increasing temperature, ejecting the bubbles away
from the heated wire. By proper choice of fluid composition, temperature, or
pressure, the sign of the surface tension gradient can be inverted such that
nucleated bubbles are attracted to the wire. As opposed to water-alcohol mixtures
that have a surface tension minimum, we show that this mixture-which we refer to
as an equilibrated vapor-liquid mixture-exhibits a surface tension maximum,
creating a unique set of behaviors which have not yet been fully examined in the
literature.
PMID- 28418679
TI - Bioresponsive Polyoxometalate Cluster for Redox-Activated Photoacoustic Imaging
Guided Photothermal Cancer Therapy.
AB - Although various types of imaging agents have been developed for photoacoustic
(PA) imaging, relatively few imaging agents exhibit high selectivity/sensitivity
to the tumor microenvironment for on-demand PA imaging and therapy. Herein,
molybdenum-based polyoxometalate (POM) clusters with the highest oxidation state
of Mo(VI) (denoted as Ox-POM) were designed as novel agents for redox-activated
PA imaging-guided photothermal therapy. Capable of escaping from recognition and
capture by the liver and spleen, these renal clearable clusters with ultrasmall
size (hydrodynamic size: 1.9 nm) can accumulate in the tumor, self-assemble into
larger nanoclusters at low pH, and are reduced to NIR absorptive agents in the
tumor microenvironment. Studies in 4T1 tumor-bearing mice indicated that these
clusters could be employed for bioresponsive PA imaging-guided tumor ablation in
vivo. Our finding is expected to establish a new physicochemical paradigm for the
design of PA imaging agents based on clusters, bridging the conventional concepts
of "molecule" and "nano" in the bioimaging field.
PMID- 28418680
TI - Dual-Functional Tamm-Dancoff Approximation: A Convenient Density Functional
Method that Correctly Describes S1/S0 Conical Intersections.
AB - Time-dependent Kohn-Sham density functional theory has been used successfully to
compute vertical excitation energies, especially for large molecular systems.
However, the lack of double excitation character in the excited amplitudes
produced by linear response in the adiabatic approximation holds it back from
broader applications in photochemistry; for example, it shows (3N - 7)
dimensional conical intersection seams (where N is the number of atoms) between
ground and excited states, although the correct dimensionality is 3N - 8. In this
letter, we present a new, conceptually simple, easy-to-implement, and easy-to-use
way to employ time-dependent Kohn-Sham density functional theory that has global
accuracy comparable with the conventional single-functional version and that
recovers the double cone topology of the potential energy surfaces at S1/S0
conical intersection seams. The new method is called the dual-functional Tamm
Dancoff approximation (DF-TDA).
PMID- 28418681
TI - Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to
Sofosbuvir, Acelarin, and INX-08189.
AB - A general and efficient method for the synthesis of pronucleotide (ProTide) 5'
phosphoramidate monoesters is reported. This method consists of a highly
stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to
afford the desired target ProTides in excellent yields without employing 3'
protection strategies. The application of this methodology to the synthesis of a
number of pharmaceutically relevant compounds currently marketed or under
investigation in clinical research is demonstrated.
PMID- 28418682
TI - Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase
Behavior and Molecular Assembly Landscapes.
AB - Asphaltenes constitute the heaviest fraction of the aromatic group in crude oil.
Aggregation and precipitation of asphaltenes during petroleum processing costs
the petroleum industry billions of dollars each year due to downtime and
production inefficiencies. Asphaltene aggregation proceeds via a hierarchical
self-assembly process that is well-described by the Yen-Mullins model.
Nevertheless, the microscopic details of the emergent cluster morphologies and
their relative stability under different processing conditions remain poorly
understood. We perform coarse-grained molecular dynamics simulations of a
prototypical asphaltene molecule to establish a phase diagram mapping the self
assembled morphologies as a function of temperature, pressure, and n
heptane:toluene solvent ratio informing how to control asphaltene aggregation by
regulating external processing conditions. We then combine our simulations with
graph matching and nonlinear manifold learning to determine low-dimensional free
energy surfaces governing asphaltene self-assembly. In doing so, we introduce a
variant of diffusion maps designed to handle data sets with large local density
variations, and report the first application of many-body diffusion maps to
molecular self-assembly to recover a pseudo-1D free energy landscape. Increasing
pressure only weakly affects the landscape, serving only to destabilize the
largest aggregates. Increasing temperature and toluene solvent fraction
stabilizes small cluster sizes and loose bonding arrangements. Although the
underlying molecular mechanisms differ, the strikingly similar effect of these
variables on the free energy landscape suggests that toluene acts upon asphaltene
self-assembly as an effective temperature.
PMID- 28418683
TI - Physical Characterization of Tobramycin Inhalation Powder: II. State Diagram of
an Amorphous Engineered Particle Formulation.
AB - Tobramycin Inhalation Powder (TIP) is a spray-dried engineered particle
formulation used in TOBI Podhaler, a drug-device combination for treatment of
cystic fibrosis (CF). A TIP particle consists of two phases: amorphous, glassy
tobramycin sulfate and a gel-phase phospholipid (DSPC). The objective of this
work was to characterize both the amorphous and gel phases following exposure of
TIP to a broad range of RH and temperature. Because, in principle, changes in
either particle morphology or the solid-state form of the drug could affect drug
delivery or biopharmaceutical properties, understanding physical stability was
critical to development and registration of this product. Studies included
morphological assessments of particles, thermal analysis to measure the gel-to
liquid crystalline phase transition (Tm) of the phospholipid and the glass
transition temperature (Tg) of tobramycin sulfate, enthalpy relaxation
measurements to estimate structural relaxation times, and gravimetric vapor
sorption to measure moisture sorption isotherms of TIP and its components.
Collectively, these data enabled development of a state diagram for TIP-a map of
the environmental conditions under which physical stability can be expected. This
diagram shows that, at long-term storage conditions, TIP is at least 50 degrees
C below the Tg of the amorphous phase and at least 40 degrees C below the Tm of
the gel phase. Enthalpy relaxation measurements demonstrate that the
characteristic structural relaxation times under these storage conditions are
many orders of magnitude greater than that at Tg. These data, along with long
term physicochemical stability studies conducted during product development,
demonstrate that TIP is physically stable, remaining as a mechanical solid over
time scales and conditions relevant to a pharmaceutical product. This met a key
design goal in the development of TIP: a room-temperature-stable formulation (3
year shelf life) that obviates the need for refrigeration for long-term storage.
This has enabled development of TOBI Podhaler-an approved inhaled drug product
that meaningfully reduces the treatment burden of CF patients worldwide.
PMID- 28418684
TI - Slow Yogic Breathing and Long-Term Cardiac Autonomic Adaptations: A Pilot Study.
AB - OBJECTIVES: To examine whether long-term practice of yogic breathing alters
cardiac autonomic control. DESIGN: Age-sex matched, cross-sectional, physiologic
pilot study. SETTINGS/LOCATION: Spaulding Rehabilitation Hospital, Cardiovascular
Laboratory, Cambridge, MA. PARTICIPANTS: Twenty-six (26) long-term yoga
practitioners and 26 age- and sex-matched controls, free of cardiovascular
disease. OUTCOME: Cardiac vagal outflow as assessed by respiratory sinus
arrhythmia (RSA). RESULTS: During unpaced (spontaneous) breathing, yoga
practitioners exhibited augmented RSA compared to controls (yoga 364.8 +/- 75.3
vs. 194.7 +/- 46.0 ms2Hz-1, p = 0.03). However, during paced breathing at 0.25 Hz
(15 breaths/min), which accounts for inter- and intravariability in breath rate,
RSA did not differ between groups (yoga 224.8 +/- 48.4 vs. 271.3 +/- 59.7 ms2Hz
1, p = 0.98). Furthermore, the relationship between age and RSA, such that RSA
declines with age, did not qualitatively differ between groups. CONCLUSIONS: Long
term practice of yogic slow breathing does not appear to augment cardiac vagal
control nor prevent known age-related declines.
PMID- 28418685
TI - Does a physical activity program in the nursing home impact on depressive
symptoms? A generalized linear mixed-model approach.
AB - OBJECTIVES: Physical activity (PA) may counteract depressive symptoms in nursing
home (NH) residents considering biological, psychological, and person-environment
transactional pathways. Empirical results, however, have remained inconsistent.
Addressing potential shortcomings of previous research, we examined the effect of
a whole-ecology PA intervention program on NH residents' depressive symptoms
using generalized linear mixed-models (GLMMs). METHOD: We used longitudinal data
from residents of two German NHs who were included without any pre-selection
regarding physical and mental functioning (n = 163, Mage = 83.1, 53-100 years;
72% female) and assessed on four occasions each three months apart. Residents
willing to participate received a 12-week PA training program. Afterwards, the
training was implemented in weekly activity schedules by NH staff. We ran GLMMs
to account for the highly skewed depressive symptoms outcome measure (12-item
Geriatric Depression Scale-Residential) by using gamma distribution. RESULTS:
Exercising (n = 78) and non-exercising residents (n = 85) showed a comparable
level of depressive symptoms at pretest. For exercising residents, depressive
symptoms stabilized between pre-, posttest, and at follow-up, whereas an increase
was observed for non-exercising residents. The intervention group's stabilization
in depressive symptoms was maintained at follow-up, but increased further for non
exercising residents. CONCLUSION: Implementing an innovative PA intervention
appears to be a promising approach to prevent the increase of NH residents'
depressive symptoms. At the data-analytical level, GLMMs seem to be a promising
tool for intervention research at large, because all longitudinally available
data points and non-normality of outcome data can be considered.
PMID- 28418688
TI - Comment on "Checklists for Image-Guided Interventions".
PMID- 28418690
TI - PI-RADS Version 2: Detection of Clinically Significant Cancer in Patients With
Biopsy Gleason Score 6 Prostate Cancer.
AB - OBJECTIVE: The purpose of this study was to analyze the utility of the Prostate
Imaging Reporting and Data System version 2 (PI-RADSv2) in the detection of a
clinically significant cancers in patients with prostate cancers with a biopsy
Gleason score of 6. MATERIALS AND METHODS: A group of 182 consecutively
registered patients with biopsy-proven prostate cancer with a Gleason score of 6
underwent MRI and radical prostatectomy. Clinically significant cancer was
surgically defined as Gleason score of 7 or greater, tumor volume of 0.5 cm3 or
greater, or tumor category T3 or greater. Clinical parameters (prostate-specific
antigen level, greatest percentage of biopsy core, and percentage of positive
cores) and the PI-RADSv2 ratings by three independent readers (experienced
readers 1 and 2, inexperienced reader 3) were investigated. Cutoffs and the
diagnostic performance of PI-RADSv2 for clinically significant cancer were
analyzed. RESULTS: Clinically significant cancer was found in 87.4% (159/182) of
patients. The cutoff PI-RADSv2 score for clinically significant cancer was 4 for
readers 1 and 2 and 5 for reader 3. The AUCs were 0.829 and 0.853 for readers 1
and 2 (p < 0.001) and 0.602 for reader 3 (p = 0.067). For reader 1, sensitivity
was 89.9% (143/159); specificity, 69.6% (16/23); positive predictive value, 95.3%
(143/150); negative predictive value, 50.0% (16/32); and accuracy, 87.4%
(159/182). The corresponding values for reader 2 were 81.1% (129/159), 82.6%
(19/23), 97.0% (129/133), 38.8% (19/49), and 81.3% (148/182). For the experienced
readers, 66.7-81.3% of patients with false-negative results had clinically
significant cancers with tumor volume less than 1 cm3. CONCLUSION: PI-RADSv2 may
help experienced readers identify clinically significant prostate cancers in
patients with a biopsy Gleason score of 6. However, some small (< 1 cm3)
clinically significant cancers can be missed when PI-RADSv2 is used.
PMID- 28418691
TI - Editor's Choice-The organization of chest pain units: Position statement of the
Acute Cardiovascular Care Association.
AB - Chest pain units are defined as organizational short stay units with specific
management protocols designed to facilitate and optimize the diagnosis of
patients presenting with chest pain in the emergency department. The present
document is intended to standardize and facilitate the installation of chest pain
units nearby to the emergency department or as an integral part of the emergency
department. Recommendations on organizational structure, physical and technical
requirements and on disease management are presented. More standardized
installation and implementation of chest pain units will enhance the quality of
chest pain units and improve the quality of care of our chest pain patients.
PMID- 28418692
TI - Drug Repurposing Patent Applications January-March 2017.
PMID- 28418689
TI - An Official American Thoracic Society Workshop Report: Chemical Inhalational
Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical
Preparedness.
AB - This report is based on the proceedings from the Inhalational Lung Injury
Workshop jointly sponsored by the American Thoracic Society (ATS) and the
National Institutes of Health (NIH) Countermeasures Against Chemical Threats
(CounterACT) program on May 21, 2013, in Philadelphia, Pennsylvania. The
CounterACT program facilitates research leading to the development of new and
improved medical countermeasures for chemical threat agents. The workshop was
initiated by the Terrorism and Inhalational Disasters Section of the
Environmental, Occupational, and Population Health Assembly of the ATS.
Participants included both domestic and international experts in the field, as
well as representatives from U.S. governmental funding agencies. The meeting
objectives were to (1) provide a forum to review the evidence supporting current
standard medical therapies, (2) present updates on our understanding of the
epidemiology and underlying pathophysiology of inhalational lung injuries, (3)
discuss innovative investigative approaches to further delineating mechanisms of
lung injury and identifying new specific therapeutic targets, (4) present
promising novel medical countermeasures, (5) facilitate collaborative research
efforts, and (6) identify challenges and future directions in the ongoing
development, manufacture, and distribution of effective and specific medical
countermeasures. Specific inhalational toxins discussed included
irritants/pulmonary toxicants (chlorine gas, bromine, and phosgene), vesicants
(sulfur mustard), chemical asphyxiants (cyanide), particulates (World Trade
Center dust), and respirable nerve agents.
PMID- 28418694
TI - Drug Repurposing Patent Applications October-December 2016.
PMID- 28418693
TI - Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila
Model of Parkinson's Disease.
AB - Parkinson's disease is a growing threat to an ever-ageing population. Despite
progress in our understanding of the molecular and cellular mechanisms underlying
the disease, all therapeutics currently available only act to improve symptoms
and do not stop the disease process. It is therefore imperative that more
effective drug discovery methods and approaches are developed, validated, and
used for the discovery of disease-modifying treatments for Parkinson's. Drug
repurposing has been recognized as being equally as promising as de novo drug
discovery in the field of neurodegeneration and Parkinson's disease specifically.
In this work, we utilize a transgenic Drosophila model of Parkinson's disease,
made by expressing human alpha-synuclein in the Drosophila brain, to validate two
repurposed compounds: astemizole and ketoconazole. Both have been computationally
predicted to have an ameliorative effect on Parkinson's disease, but neither had
been tested using an in vivo model of the disease. After treating the flies in
parallel, results showed that both drugs rescue the motor phenotype that is
developed by the Drosophila model with age, but only ketoconazole treatment
reversed the increased dopaminergic neuron death also observed in these models,
which is a hallmark of Parkinson's disease. In addition to validating the
predicted improvement in Parkinson's disease symptoms for both drugs and
revealing the potential neuroprotective activity of ketoconazole, these results
highlight the value of Drosophila models of Parkinson's disease as key tools in
the context of in vivo drug discovery, drug repurposing, and prioritization of
hits, especially when coupled with computational predictions.
PMID- 28418695
TI - A Comparison of Different Staging Systems for Multiple Myeloma: Can the MRI
Pattern Play a Prognostic Role?
AB - OBJECTIVE: The objective of this study is to compare the most recent systems for
the staging of multiple myeloma (MM), the Durie-Salmon PLUS system and the
International Staging System, according to patients' survival rates and response
to therapy. Another objective is to verify whether patterns of bone marrow
alteration on MRI (i.e., focal, diffuse, or variegated patterns) can provide
prognostic information for patients with MM. MATERIALS AND METHODS: We
retrospectively enrolled 85 patients with MM who were monitored for a minimum of
6 years and who underwent contrast-enhanced spinal and pelvic MRI at 1.5 T and
whole-body FDG PET/CT at the time of diagnosis. Patients underwent MM staging
performed using both staging systems and were divided into groups on the basis of
their MRI patterns. These patient groups were then compared in terms of survival,
response to therapy, and duration of response. RESULTS: Both staging systems
showed great capability in differentiating patients with a worse prognosis from
patients with a better outcome, with the capability of both systems found to be
statistically significant, albeit less statistically significant for the Durie
Salmon PLUS system (p = 0.010 vs p = 0.046, respectively). Patients with a focal
pattern on MRI had a worse survival rate than did the patients with other MRI
patterns (p = 0.032). CONCLUSION: These data indicate that both the International
Staging System and the Durie-Salmon PLUS system have great potential for
characterizing and stratifying MM to determine the survival outcome and therapy
response of patients. Observation of a focal pattern on MRI seems to be
associated with poorer survival.
PMID- 28418696
TI - Eccentric Exercise, Kinesiology Tape, and Balance in Healthy Men.
AB - CONTEXT: Deficits in balance have been identified as a possible risk factor for
knee injuries in athletes. Despite a lack of evidence for its effectiveness,
kinesiology tape (KT) is widely used to prevent knee injuries. OBJECTIVE: To
investigate the influence of KT at the knee joint on balance ability in healthy
men after eccentric exercise. DESIGN: Crossover study. SETTING: University
laboratory. PATIENTS OR OTHER PARTICIPANTS: Twelve young men with no history of
lower limb injury volunteered for the study (age = 23.3 +/- 2.6 years). All
participants were students enrolled in a sports science program. INTERVENTION(S):
Participants performed the balance test with and without KT at the knee joint
on 2 separate days. MAIN OUTCOME MEASURE(S): The ability to maintain balance
was assessed during a single-legged-stance test using a computerized balance
stability test system. The test was performed before and after 30 minutes of
downhill walking on a treadmill. RESULTS: Eccentric exercise resulted in a
deterioration of balance ability, which was attenuated by the use of KT. Further
analyses revealed that the effectiveness of KT depended on the participant's
balance status, with the preventive effect being greater in participants
presenting with poorer baseline balance ability. CONCLUSIONS: Applied to the
knee joint, KT counteracted the exercise-related deterioration of balance ability
observed when no tape was used. Participants presenting with below-average
balance ability received more benefit from KT. By preventing exercise-related
impairment of balance ability, KT might help to reduce the risk of sport
associated knee injuries.
PMID- 28418698
TI - Incidence and Risk Factors of Mastitis in Shiraz, Iran: Results of a Cohort
Study.
AB - BACKGROUND: Approximately one in five Western women who breastfeed are likely to
experience acute mastitis. This study investigated the incidence and risk factors
of acute mastitis in a cohort of Iranian women. SUBJECTS AND METHODS: Subjects
were 672 participants of the Shiraz Infant Feeding Study conducted between June
2014 and March 2015. Mothers were recruited from the maternity ward and followed
up at 1, 3, 4, and 6 months postpartum to obtain information on their
breastfeeding practices and experiences. The occurrence of acute mastitis in the
first 26 weeks postpartum was self-reported and the occurrence of acute mastitis
in the first 4 weeks and between 5 and 12 weeks postpartum was treated as
separate outcomes. The risk factors for acute mastitis were explored using
multivariable logistic regression analysis. RESULTS: In total, 130 mothers
(19.3%, 95% confidence interval: 16.3-22.3%) experienced at least one episode of
acute mastitis. Having expressed breast milk and use of a pacifier were
significantly associated with acute mastitis in both the first 4 weeks and
between 5 and 12 weeks postpartum. Persistent problems with cracked or sore
nipples, or engorged breasts, and a reduction in breastfeeding were associated
with acute mastitis between 5 and 12 weeks. CONCLUSIONS: The incidence of acute
mastitis experienced by this cohort of Iranian women is similar to that reported
for women in Western countries. The risk factors of acute mastitis identified in
this study are potentially modifiable and could be prevented or ameliorated with
adequate support and anticipatory guidance provided in the early postpartum
period.
PMID- 28418699
TI - Candida Endocarditis Presenting as Acute Myocardial Infarction.
PMID- 28418700
TI - Three-dimensional analysis of upper airway morphology in skeletal Class III
patients with and without mandibular asymmetry.
AB - OBJECTIVE: To compare the three-dimensional (3D) morphology of the upper airway
in skeletal Class III patients with and without mandibular asymmetry and to
investigate the possible underlying correlations between the morphology of the
upper airway and mandibular deviation. MATERIALS AND METHODS: Cone-beam computed
tomography images of 54 subjects with skeletal Class III malocclusion (ANB angle
<= 0.4 degrees , Wits <= -5.5 degrees ) were taken and 3D upper airway models
were reconstructed using Dolphin 3D software. According to the distance (d) from
symphysis menti to the sagittal plane, all subjects were divided into a symmetry
group (d <= 2 mm) and an asymmetry group (d >= 4 mm). Based on the severity of
mandibular deviation, the asymmetry group was divided into subgroup I (4 mm <=d
<10 mm) and subgroup II (d >= 10 mm). Cross-sectional linear distances, areas,
and volumetric variables of the upper airway were measured in the 3D airway
model. RESULTS: Width of the inferior limit of the glossopharynx (P3W), cross
sectional area of the anterior limit of the nasal airway (P5S), and height of the
glossopharynx (GPH) in the asymmetry group were significantly larger than in the
symmetry group. As for subjects with severe mandibular deviation in subgroup II
(d >= 10 mm), volume of the glossopharynx (GPV), total volume of the pharynx
(TPV), length of the inferior limit of the velopharynx (P2L), and ratio of length
to width of the inferior limit of the velopharynx (P2L/P2W) showed significantly
negative correlations with mandibular deviation (r > 0.7, P < .05). CONCLUSIONS:
In Class III subjects with severe mandibular asymmetry, the pharyngeal airway
showed a tendency toward constriction and presented a more elliptical shape as
mandibular deviation became more severe (P < .01).
PMID- 28418697
TI - A Two-Biomarker Model Predicts Mortality in the Critically Ill with Sepsis.
AB - RATIONALE: Improving the prospective identification of patients with systemic
inflammatory response syndrome (SIRS) and sepsis at low risk for organ
dysfunction and death is a major clinical challenge. OBJECTIVES: To develop and
validate a multibiomarker-based prediction model for 28-day mortality in
critically ill patients with SIRS and sepsis. METHODS: A derivation cohort (n =
888) and internal test cohort (n = 278) were taken from a prospective study of
critically ill intensive care unit (ICU) patients meeting two of four SIRS
criteria at an academic medical center for whom plasma was obtained within 24
hours. The validation cohort (n = 759) was taken from a prospective cohort
enrolled at another academic medical center ICU for whom plasma was obtained
within 48 hours. We measured concentrations of angiopoietin-1, angiopoietin-2, IL
6, IL-8, soluble tumor necrosis factor receptor-1, soluble vascular cell adhesion
molecule-1, granulocyte colony-stimulating factor, and soluble Fas. MEASUREMENTS
AND MAIN RESULTS: We identified a two-biomarker model in the derivation cohort
that predicted mortality (area under the receiver operator characteristic curve
[AUC], 0.79; 95% confidence interval [CI], 0.74-0.83). It performed well in the
internal test cohort (AUC, 0.75; 95% CI, 0.65-0.85) and the external validation
cohort (AUC, 0.77; 95% CI, 0.72-0.83). We determined a model score threshold
demonstrating high negative predictive value (0.95) for death. In addition to a
low risk of death, patients below this threshold had shorter ICU length of stay,
lower incidence of acute kidney injury, acute respiratory distress syndrome, and
need for vasopressors. CONCLUSIONS: We have developed a simple, robust biomarker
based model that identifies patients with SIRS/sepsis at low risk for death and
organ dysfunction.
PMID- 28418701
TI - Cementogenesis is inhibited under a mechanical static compressive force via
Piezo1.
AB - OBJECTIVE: To investigate whether Piezo1, a mechanotransduction gene mediates the
cementogenic activity of cementoblasts under a static mechanical compressive
force. MATERIALS AND METHODS: Murine cementoblasts (OCCM-30) were exposed to a
2.0 g/cm2 static compressive force for 3, 6, 12, and 24 hours. Then the
expression profile of Piezo1 and the cementogenic activity markers
osteoprotegerin (Opg), osteopontin (Opn), osteocalcin (Oc), and protein tyrosine
phosphataselike member A (Ptpla) were analyzed. Opg, Opn, Oc, and Ptpla
expression was further measured after using siRNA to knock down Piezo1. Real-time
PCR, Western blot, and cell proliferation assays were performed according to
standard procedures. RESULTS: After mechanical stimulation, cell morphology and
proliferation did not change significantly. The expression of Piezo1, Opg, Opn,
Oc, and Ptpla was significantly decreased, with a high positive correlation
between Opg and Piezo1 expression. After Piezo1 knockdown, the expression of Opg,
Opn, Oc, and Ptpla was further decreased under mechanical stimulation.
CONCLUSIONS: Cementogenic activity was inhibited in OCCM-30 cells under static
mechanical force, a process that was partially mediated by the decrease of
Piezo1. This study provides a new viewpoint of the pathogenesis mechanism of
orthodontically induced root resorption and repair.
PMID- 28418702
TI - Pancreatic Calcifications and Calcified Pancreatic Masses: Pattern Recognition
Approach on CT.
AB - OBJECTIVE: The purpose of this article is to review a spectrum of calcified
pancreatic masses and propose an algorithm for diagnostic radiologic evaluation.
CONCLUSION: Pancreatic calcifications are being detected more frequently because
of the widespread use of imaging, particularly CT. Pancreatic calcifications are
most commonly associated with chronic pancreatitis related to alcohol abuse.
Several other pathologic entities, however, can cause pancreatic calcifications.
Familiarity with these entities and their CT appearance is helpful in making an
accurate diagnosis.
PMID- 28418703
TI - Radioresistance of Adenine to Cosmic Rays.
AB - The presence of nucleobases in carbonaceous meteorites on Earth is an indication
of the existence of this class of molecules in outer space. However, space is
permeated by ionizing radiation, which can have damaging effects on these
molecules. Adenine is a purine nucleobase that amalgamates important biomolecules
such as DNA, RNA, and ATP. Adenine has a unique importance in biochemistry and
therefore life. The aim of this work was to study the effects of cosmic ray
analogues on solid adenine and estimate its survival when exposed to corpuscular
radiation. Adenine films were irradiated at GANIL (Caen, France) and GSI
(Darmstadt, Germany) by 820 MeV Kr33+, 190 MeV Ca10+, 92 MeV Xe23+, and 12 MeV
C4+ ion beams at low temperature. The evolution of adenine molecules under heavy
ion irradiation was studied by IR absorption spectroscopy as a function of
projectile fluence. It was found that the adenine destruction cross section
(sigmad) follows an electronic stopping power (Se) power law under the form:
CSen; C is a constant, and the exponential n is a dimensionless quantity. Using
the equation above to fit our results, we determined sigmad = 4 * 10-17 Se1.17,
with Se in kiloelectronvolts per micrometer (keV MUm-1). New IR absorption bands
arise under irradiation of adenine and can be attributed to HCN, CN-, C2H4N4,
CH3CN, and (CH3)3CNC. These findings may help to understand the stability and
chemistry related to complex organic molecules in space. The half-life of solid
adenine exposed to the simulated interstellar medium cosmic ray flux was
estimated as (10 +/- 8) * 106 years. Key Words: Heavy ions-Infrared spectroscopy
Astrochemistry-Cosmic rays-Nucleobases-Adenine. Astrobiology 17, 298-308.
PMID- 28418705
TI - Accurate Differentiation of Carotenoid Pigments Using Flight Representative Raman
Spectrometers.
AB - Raman spectrometers will be utilized on two Mars rover missions, ExoMars and Mars
2020, in the near future, to search for evidence of life and habitable geological
niches on Mars. Carotenoid pigments are recognized target biomarkers, and as they
are highly active in Raman spectroscopy, they can be readily used to characterize
the capabilities of space representative instrumentation. As part of the
preparatory work being performed for the ExoMars mission, a gypsum crust
colonized by microorganisms was interrogated with commercial portable Raman
instruments and a flight representative Raman laser spectrometer. Four separate
layers, each exhibiting different coloration resulting from specific halophilic
microorganism activities within the gypsum crust, were studied by using two
excitation wavelengths: 532 and 785 nm. Raman or fluorescence data were readily
obtained during the present study. Gypsum, the main constituent of the crust, was
detected with both excitation wavelengths, while the resonance Raman signal
associated with carotenoid pigments was only detected with a 532 nm excitation
wavelength. The fluorescence originating from bacteriochlorophyll a was found to
overwhelm the Raman signal for the layer colonized by sulfur bacteria when
interrogated with a 785 nm excitation wavelength. Finally, it was demonstrated
that portable instruments and the prototype were capable of detecting a
statistically significant difference in band positions of carotenoid signals
between the sample layers. Key Words: Gypsum-Raman spectrometers-Carotenoids
ExoMars-Mars exploration-Band position shift. Astrobiology 17, 351-362.
PMID- 28418704
TI - False Negatives for Remote Life Detection on Ocean-Bearing Planets: Lessons from
the Early Earth.
AB - Ocean-atmosphere chemistry on Earth has undergone dramatic evolutionary changes
throughout its long history, with potentially significant ramifications for the
emergence and long-term stability of atmospheric biosignatures. Though a great
deal of work has centered on refining our understanding of false positives for
remote life detection, much less attention has been paid to the possibility of
false negatives, that is, cryptic biospheres that are widespread and active on a
planet's surface but are ultimately undetectable or difficult to detect in the
composition of a planet's atmosphere. Here, we summarize recent developments from
geochemical proxy records and Earth system models that provide insight into the
long-term evolution of the most readily detectable potential biosignature gases
on Earth-oxygen (O2), ozone (O3), and methane (CH4). We suggest that the
canonical O2-CH4 disequilibrium biosignature would perhaps have been challenging
to detect remotely during Earth's ~4.5-billion-year history and that in general
atmospheric O2/O3 levels have been a poor proxy for the presence of Earth's
biosphere for all but the last ~500 million years. We further suggest that
detecting atmospheric CH4 would have been problematic for most of the last ~2.5
billion years of Earth's history. More broadly, we stress that internal oceanic
recycling of biosignature gases will often render surface biospheres on ocean
bearing silicate worlds cryptic, with the implication that the planets most
conducive to the development and maintenance of a pervasive biosphere will often
be challenging to characterize via conventional atmospheric biosignatures. Key
Words: Biosignatures-Oxygen-Methane-Ozone-Exoplanets-Planetary habitability.
Astrobiology 17, 287-297.
PMID- 28418706
TI - Radiation-Driven Formation of Reactive Oxygen Species in Oxychlorine-Containing
Mars Surface Analogues.
AB - The present study demonstrates that gamma-radiolyzed perchlorate-containing Mars
soil salt analogues (in a CO2 atmosphere) generate upon H2O wetting the reactive
oxygen species (ROS) superoxide radical (O2*-), hydrogen peroxide (H2O2), and
hydroxyl radicals (*OH). This study also validates that analogue radiolysis forms
oxychlorine species that, in turn, can UV-photolyze to *OH upon UV photolysis.
This investigation was made possible by the development of a new assay for
inorganic-origin O2*- and H2O2 determination and by the modification of a
previous assay for soil *OH. Results show that radiolyzed Mg(ClO4)2 generates
H2O2 and *OH; and when included as part of a mixture analogous to the salt
composition of samples analyzed at the Mars Phoenix site, the analogue generated
O2*-, H2O2, and *OH, with *OH levels 150-fold higher than in the radiolyzed
Mg(ClO4)2 samples. Radiolyzed Mars Phoenix site salt analogue that did not
contain Mg(ClO4)2 generated only *OH also at 150-fold higher concentration than
Mg(ClO4)2 alone. Additionally, UV photolysis of the perchlorate gamma radiolysis
product chlorite (ClO2-) generated the oxychlorine products trihalide (Cl3-),
chlorine dioxide (ClO2*), and hypochlorite (ClO-), with the formation of *OH by
UV photolysis of ClO-. While the generation of ROS may have contributed in part
to 14CO2 production in the Viking Labeled Release (LR) experiment and O2 (g)
release in the Viking Gas Exchange (GEx) experiment, our results indicate that
they are not likely to be the major contributor to the LR and GEx results.
However, due to their highly reactive nature, they are expected to play a
significant role in the alteration of organics on Mars. Additionally, experiments
with hypochlorite show that the thermal stability of NaClO is in the range of the
thermal stability observed for thermally liable oxidant responsible for the
Viking LR results. Key Words: Mars-Oxygen-Salts-Radiation-Habitability.
Astrobiology 17, 319-336.
PMID- 28418708
TI - Long Trekking Experience at High Altitude Causes Testicular Volumetric Reduction
in Humans: Evidence Based on Magnetic Resonance Imaging.
PMID- 28418707
TI - Liquid Water Restricts Habitability in Extreme Deserts.
AB - Liquid water is a requirement for biochemistry, yet under some circumstances it
is deleterious to life. Here, we show that liquid water reduces the upper
temperature survival limit for two extremophilic photosynthetic microorganisms
(Gloeocapsa and Chroococcidiopsis spp.) by greater than 40 degrees C under
hydrated conditions compared to desiccated conditions. Under hydrated conditions,
thermal stress causes protein inactivation as shown by the fluorescein diacetate
assay. The presence of water was also found to enhance the deleterious effects of
freeze-thaw in Chroococcidiopsis sp. In the presence of water, short-wavelength
UV radiation more effectively kills Gloeocapsa sp. colonies, which we hypothesize
is caused by factors including the greater penetration of UV radiation into
hydrated colonies compared to desiccated colonies. The data predict that deserts
where maximum thermal stress or irradiation occurs in conjunction with the
presence of liquid water may be less habitable to some organisms than more
extreme arid deserts where organisms can dehydrate prior to being exposed to
these extremes, thus minimizing thermal and radiation damage. Life in extreme
deserts is poised between the deleterious effects of the presence and the lack of
liquid water. Key Words: Deserts-Extremophiles-Stress-High temperatures-UV
radiation-Desiccation. Astrobiology 17, 309-318.
PMID- 28418709
TI - Psychological Assessment With the MMPI-2/MMPI-2-RF, 3rd ed., by A. F. Friedman,
P. K. Bolinskey, R. W. Levak, & D. S. Nichols.
PMID- 28418710
TI - Lung cancer guidelines in Sweden, Denmark, Norway and Finland: a comparison.
AB - BACKGROUND: The Nordic countries are similar in terms of demographics and health
care organization. Yet there are marked differences in lung cancer mortality, for
which Denmark historically has had the poorest outcome. One of several possible
reasons for these differences could have to do with how lung cancer is diagnosed
and treated in the different Nordic countries. However, among the four most
populous Nordic countries: Sweden, Denmark, Norway and Finland, there is a
paucity of knowledge about differences and similarities in recommendations in the
national guidelines for non-small cell lung cancer (NSCLC) and the methodology by
which the guidelines are developed. METHODS: We identified and evaluated the
development and content of the available clinical care guidelines for NSCLC in
the four countries. Moreover, we compared the integrated cancer pathways in these
countries. We have used case examples to illustrate areas with clear differences
in clinical care recommendations. RESULTS: There are notable differences in the
methodology by which the guidelines are developed, published and updated to
comply with international recommendations. The Norwegian guidelines are developed
and updated according to the most rigorous methodology and have so far been
updated most frequently. We found that on the basis of recommendations patients
with NSCLC are treated differently with regard to bevacizumab therapy and
radiation dosing regimens. Cerebral imaging practices in patients with locally
advanced NSCLC also differ. There is, moreover, a marked difference with regard
to efforts to help patients to quit smoking. All except Finland have integrated
cancer pathways for fast track diagnosis and treatment. Guidelines for follow-up
of lung cancer patients also differ, with the Danish follow-up regimen as the
most comprehensive. To obtain consensus on optimal clinical care, areas with
differences in recommendations or where recommendations are based on a low level
of evidence should be subjected to further studies.
PMID- 28418711
TI - Silibinin Improves TNF-alpha and M30 Expression and Histological Parameters in
Rat Kidneys After Hepatic Ischemia/Reperfusion.
AB - BACKGROUND: Remote kidney damage is a sequel of hepatic ischemia-reperfusion
(I/R) injury. Silibinin is the main ingredient of the milk thistle plant seed
extract with known antioxidant and hepatoprotective activity. Our study
investigates the nephroprotective potential of intravenously administered
silibinin, as a lyophilized SLB-hydoxypropyl-beta-cyclodextrin product, in
hepatic I/R injury. MATERIAL AND METHODS: 63 Wistar rats were divided into three
groups: Sham (virtual intervention); Control (45 min ischemia and reperfusion);
and Silibinin (200 MUL intravenous silibinin administration after 45 min of
ischemia). Kidney tissues were collected to determine TNF-alpha, M30 and
histopathological changes at predetermined time intervals. RESULTS: Comparing
Sham vs. Control groups, proved that hepatic I/R injury increased renal TNF-alpha
and M30 expression. Deterioration was observed in hyperemia/filtration of renal
parenchyma and tubules, cortical filtration, tubular necrosis and edema (tissue
swelling index). Intravenous silibinin administration and comparison of the
Control vs. Silibinin groups showed a statistically significant decrease in TNF
alpha levels at 240 min following I/R (p < 0.0001), and in M30 at 180 min (p =
0.03) and 240 min (p < 0.0001). Renal parameters have significantly decreased in:
hyperemia/filtration of renal parenchyma at 120 min (p = 0.003), 180 min (p =
0.0001) and 240 min (p = 0.0002); hyperemia/filtration of renal tubules at 120
min (p = 0.02), 180 min (p = 0.0001) and 240 min (p = 0.0005); cortical
filtration (240 min - p = 0.005); tubular necrosis (240 min - p = 0.021); and
edema (240 min - p = 0.001). CONCLUSION: Our study confirms that hepatic I/R
injury causes remote renal damage while the intravenous administration of
silibinin leads to statistically significant nephroprotective action.
PMID- 28418712
TI - A Cross-Sectional Study of Indoor Tanning in Fitness Centres.
AB - BACKGROUND: Ultraviolet (UV) radiation is a human carcinogen and is associated
with the development of skin cancer. The promotion of indoor tanning (IT) at
fitness centres is of particular concern as it reinforces the idea that a tan is
associated with health and fitness. The purpose of this study was to investigate
the prevalence of IT in fitness centres, with an emphasis on determining the
financial costs, adherence to regulations, and safety precautions. METHODS: Ten
cities, representing 9 different Canadian provinces, were chosen for the study.
From each province, a minimum of 20 and a maximum of 30 fitness centres were
randomly selected from the Yellow Pages website. Each fitness centre was
contacted by the principal investigator and inquiries were made from a consumer's
perspective. RESULTS: Of the 203 gyms surveyed, 43% (88/203) offered tanning
facilities. Of these, 10.23% (9/88) were found to be noncompliant with the
provincial IT regulations for age and/or time between tanning sessions.
INTERPRETATION: Despite the known risks of IT, not all fitness centres are
compliant with provincial legislations regarding IT, and some continue to promote
tanning access to minors.
PMID- 28418713
TI - Defence factors of vaginal lactobacilli.
AB - Accurate knowledge of the composition and ecology of the vaginal microbial
environment in healthy women is necessary for understanding lactobacilli
dominated normal microbiota and the mechanisms by which it reduces disease risk.
The vagina and its microbiota form a balanced ecosystem; any movement outside the
normal range for this ecosystem of obligate and/or facultative microbes, termed
dysbacteriosis, can lead to infection and disease. This review summarizes recent
research on the vaginal ecosystem, the Lactobacillus species that dominate it,
and the means by which they suppress the growth, development, and/or
proliferation of pathogenic microbial species. Lactobacilli colonization is
believed to be beneficial since it prevents other microorganisms from colonizing
the vaginal epithelium via competitive adhesion, interactions with the local
immunity and plasminogen-plasmin system, and the production of lactic acid,
hydrogen peroxide, and antibacterial substances. In addition, lactobacilli also
constitute an important part of the urogenital tract microbiota and the
lactobacilli-dominated vaginal microbiome is a major determinant for female
urogenital health.
PMID- 28418714
TI - More Than a Physical Burden: Women's Mental and Emotional Work in Preventing
Pregnancy.
AB - In the United States, responsibility for preventing pregnancy in heterosexual
relationships disproportionately falls on women. While the biotechnological
landscape of available methods may explain the assignment of the physical burden
for contraception to women, this does not mean the concomitant time, attention,
and stress that preventing pregnancy requires must also be primarily assumed by
women. Building on work identifying health care providers as contributors to the
construction of normative ideas about reproduction, this study analyzed 52
contraceptive counseling visits with women who reported they did not want future
children for the construction of responsibility for the mental and emotional
aspects of contraception. Offering a case of how gender inequality is
(re)produced through clinical encounters, findings demonstrate that clinicians
discursively constructed these responsibilities as women's and point to
structural aspects of the visit itself that reify this unequal burden as normal.
Results are consistent with research identifying the broader feminization of
family health work in heterosexual relationships. To the extent that the
distribution of the mental and emotional responsibilities of preventing pregnancy
is both a product of and contributor to gender inequality, this analysis yields
insight into the production-and possible deconstruction-of (reproductive) health
care as a gendered social structure.
PMID- 28418715
TI - Evaluation of Selective-Enrichment and Chromogenic Media for Salmonella Detection
in Raw Shell Egg Contents with a Low Microbial Load.
AB - The current study was conducted to evaluate the ability to recover Salmonella
from shell egg contents by culture methods. A total of 4,000 eggs were obtained
from a grading and packing center located in the Gyeonggi Province of South
Korea, and 200 samples were created by pooling 20 broken eggs. The pooled samples
were held at room temperature for 4 d before a 25-mL aliquot of each pool was
added to 225 mL of modified trypticase soy broth (mTSB) and incubated at 35
degrees C for 24 +/- 2 h. A loopful of the culture was streaked onto chromogenic
Druggan-Forsythe-Iversen (DFI) agar and incubated at 36 +/- 1 degrees C for 18-24
h. In addition, 1 mL and/or 0.1 mL of the mTSB cultures were added to 10 mL of
Muller-Kauffmann tetrathionate with novobiocin (MKTTn) or Rappaport-Vassiliadis
(RV) broth, and they were incubated for 24 +/- 2 h at 35 +/- 2 degrees C or 42 +/
0.2 degrees C, respectively. A loopful from these cultures was streaked onto
Brilliant Green (BG), xylose lysine deoxycholate (XLD), and bismuth sulfite (BS)
agar plates, respectively. Directly streaking onto DFI agar revealed the presence
of Salmonella in 14 out of the 200 pooled samples (7%); whereas the combination
of RV medium and BG, XLD, and BS agar detected the pathogen in only 9 (4.5%), 7
(3.5%), and 3 (1.5%) of the pooled samples, respectively. When MKTTn broth was
used, Salmonella was detected in 7 (3.5%), 2 (1%), and 0 (0%) of the samples when
streaked onto BG, XLD, and BS agar, respectively. The results indicate that
direct plating onto DFI agar without enrichment was the most suitable among the
methods evaluated in this study for detecting Salmonella in raw shell egg
contents with a low microbial load.
PMID- 28418716
TI - Development and Initial Validation of the Five-Factor Model Adolescent
Personality Questionnaire (FFM-APQ).
AB - This research reports on the 4-phase development of the 25-item Five-Factor Model
Adolescent Personality Questionnaire (FFM-APQ). The purpose was to develop and
determine initial evidence for validity of a brief adolescent personality
inventory using a vocabulary that could be understood by adolescents up to 18
years old. Phase 1 (N = 48) consisted of item generation and expert (N = 5)
review of items; Phase 2 (N = 179) involved item analyses; in Phase 3 (N = 496)
exploratory factor analysis assessed the underlying structure; in Phase 4 (N =
405) confirmatory factor analyses resulted in a 25-item inventory with 5
subscales.
PMID- 28418717
TI - Diversity of Endophytic Bacteria in a Fern Species Dryopteris uniformis (Makino)
Makino and Evaluation of Their Antibacterial Potential Against Five Foodborne
Pathogenic Bacteria.
AB - The fern plant Dryopteris uniformis has traditionally been used in herbal
medicine and possesses many biological activities. This study was conducted to
explore the endophytic bacterial diversity associated with D. uniformis and
evaluate their antibacterial potential against foodborne pathogenic bacteria
(FPB). Among 51 isolated endophytic bacteria (EB), 26 EB were selected based on
their morphological characteristics and identified by 16S rRNA gene analysis. The
distribution of EB was diverse in the leaf and the stem/root tissues. When the EB
were screened for antibacterial activity against five FPB, Listeria
monocytogenes, Salmonella Typhimurium, Bacillus cereus, Staphylococcus aureus,
and Escherichia coli O157:H7, four EB Bacillus sp. cryopeg, Paenibacillus sp.
rif200865, Staphylococcus warneri, and Bacillus psychrodurans had a broad
spectrum of antibacterial activity (9.58 +/- 0.66 to 21.47 +/- 0.27 mm inhibition
zone). The butanol solvent extract of B. sp. cryopeg and P. sp. rif200865
displayed effective antibacterial activity against the five FPB, which was
evident from the scanning electron microscopy with irregular or burst cell
morphology in the EB-treated bacteria compared to smooth and regular cells in
case of the control bacteria. The minimum inhibitory concentration and minimum
bactericidal concentration values ranged between 250-500 MUg/mL and 500-100
MUg/mL, respectively. The above outcomes signify the huge prospective of the
selected EB in the food industry. Overall, the above results suggested that D.
uniformis contains several culturable EB that possess effective antibacterial
compounds, and that EB can be utilized as a source of natural antibacterial
agents for their practical application in food industry to control the spread of
FPB as a natural antibacterial agent.
PMID- 28418718
TI - Socially Interactive and Passive Technologies Enhance Friendship Quality: An
Investigation of the Mediating Roles of Online and Offline Self-Disclosure.
AB - Previous studies indicate that characteristics of social-based technologies (STs)
stimulate the sharing of intimate information online, which in turn enhances the
quality of friendships. In addition, intimate online self-disclosure has been
positively associated with offline self-disclosure. One objective of the current
study was to combine the literature and test a model which postulates that STs
use stimulates online self-disclosure which facilitates offline self-disclosure
and, thereby, enhances the quality of close friendships. A second objective of
this study was to examine if the aforementioned model applies to two categories
of STs, including socially interactive technologies (SITs; e.g., instant
messaging) and socially passive technologies (SPTs; e.g., reading posts on social
networking sites). An online survey was conducted with 212 young adults between
18 and 25 years of age. The proposed indirect positive effects of SITs and SPTs
use on the quality of friendships were supported. The positive effect of SITs use
on the quality of friendships was explained entirely by the young adults'
disclosure of personal information when using SITs which facilitated intimate
self-disclosure during face-to-face interactions. Although there was not a direct
effect of SPTs use on the quality of friendships, SPTs use was positively related
to SPTs self-disclosure, which had a positive effect on offline self-disclosure.
The current study enhances our understanding regarding the positive effects
associated with the use of STs among close friends and identifies the
contribution of online self-disclosure for offline interactions.
PMID- 28418719
TI - The Incremental Validity of Self-Report and Performance-Based Methods for
Assessing Hostility to Predict Cardiovascular Disease in Physicians.
AB - We evaluated the utility of an integrative, multimethod approach for assessing
hostility-related constructs to predict premature cardiovascular disease (CVD)
and premature coronary heart disease (CHD) using participants from the Johns
Hopkins Precursors Study, which was designed to identify risk factors for heart
disease. Participants were assessed at baseline while in medical school from 1946
to 1962 (M age = 24.6) and have been followed annually since then. Baseline
assessment included individually administered Rorschach protocols (N = 416)
scored for aggressive imagery (i.e., Aggressive Content, Aggressive Past) and
self-reports of 3 possible anger responses to stress. Cox regression analyses
predicting morbidity or mortality by age 55 revealed a significant interaction
effect; high levels of Aggressive Content with high self-reported hostility
predicted an increased rate of premature CVD and CHD, and incrementally predicted
the rate of these events after controlling for the significant covariates of
smoking (CVD and CHD) and cholesterol (CHD) that were also assessed at baseline.
The hostility and anger measures, as well as other baseline covariates, were not
predictors of CVD risk factors assessed at midlife during follow-up. Overall,
this integrative model of hostility illustrates the potential value of
multimethod assessment to areas of health psychology and preventive medicine.
PMID- 28418720
TI - Effectiveness and outcomes of thermablate endometrial ablation system in women
with heavy menstrual bleeding.
AB - Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age
group with major impact on their quality of life (QoL). The aim was to study the
short-term effectiveness of Thermablate Endometrial Ablation System (EAS) and its
impact on QoL in women with HMB. This was a prospective cohort study conducted on
consecutive 72 women suffering from HMB. The success rate was estimated and
patients' QoL was compared before and after the procedure using the Aberdeen
menorrhagia severity scale. The mean follow-up period was 18 months (6-24
months). The mean age and body mass index were 48 (+/-5.2) years 33.2 (+/-7.4)
kg/m2 respectively. Among treated participants, 58 (80.6%) reported the absence
of bleeding. A significant decrease was observed in the rate of missed social
activity and increase in the leisure time activities. The overall patient
satisfaction was 95.7%. Thermablate EAS is an effective minimally invasive
treatment with marked improvement in QoL in women with HMB. Impact statement
Heavy menstrual bleeding (HMB) is a common problem that affects 11-13% of
reproductive age women with major impact on their quality of life (QoL). A
variety of methods for endometrial ablation has been used for the destruction of
the endometrial lining to treat HMB. The short-term results of this study shows
amenorrhoea rate of (80.6%) after the procedure and a significant decrease in the
rate of missed social activity and increase in the leisure time activities with
marked improvement in QoL. The overall patient satisfaction was 95.7%.
Thermablate Endometrial Ablation System is an effective minimally invasive
treatment for HMB with advantages of shorter operating time, shorter hospital
stay and high-level patient satisfaction. However, further clinical research with
large-scale studies and possible comparison with other treatment options are
recommended.
PMID- 28418722
TI - Correction to: Patient Personality and Relational Patterns in Psychotherapy:
Factor Structure, Reliability, and Validity of the Psychotherapy Relationship
Questionnaire.
PMID- 28418721
TI - Practical Applications of Generalizability Theory for Designing, Evaluating, and
Improving Psychological Assessments.
AB - In this article, we illustrate how generalizability theory (G-theory) can extend
traditional assessment methods for designing, improving, and evaluating results
from both objectively and subjectively scored measures of individual differences.
Our illustrations include quantification of multiple sources of measurement
error, derivation of unique indexes of consistency for norm- and criterion
referenced interpretations of scores, estimation of score consistency when
changing a measurement procedure, and disattenuation of correlation coefficients
for measurement error. We also expand G-theory analyses beyond the item level to
include parcels and split measures and highlight linkages among G-theory,
classical test theory, and structural equation modeling. Computer code and sample
data are provided in online supplements to help readers apply the demonstrated
techniques to their own assessments.
PMID- 28418723
TI - Ethnomedical and Sociocultural Factors of Pica Substances in Rural South India.
AB - Pica, the intentional ingestion of culturally determined "nonfood" substances,
occurs cross-culturally and most commonly during pregnancy. The current study
describes women's perceptions of ethnomedical and sociocultural aspects of pica
along with familial acquisition and transmission of knowledge and behaviors in a
South Indian population. Findings showed that in contrast to Western models of
pica, nonfood consumption is not entirely taboo; consumers rely on local remedies
to cure overconsumption; and perceptions of prevalence extend beyond pregnancy.
Future research on pica should consider consumption patterns outside of pregnancy
and the role stigma plays in individuals seeking assistance for overconsumption.
PMID- 28418724
TI - Long Noncoding RNA MEG3 Negatively Regulates Proliferation and Angiogenesis in
Vascular Endothelial Cells.
AB - Long noncoding RNA (lncRNA) MEG3 is an important tumor suppressor in several
types of human cancers. However, the biological function and underlying mechanism
of MEG3 in vascular endothelial cells (VECs) remain unknown. In the present
study, we demonstrated the functional importance of lncRNA MEG3 in proliferation
and angiogenesis of VECs. MEG3 overexpression significantly suppressed the
proliferation and in vitro angiogenesis in VECs, whereas knockdown of MEG3 had
the opposite effect. Furthermore, we found that MEG3 exerts its function through
negatively regulating miR-9 by acting as a microRNA sponge. Taken together, MEG3
miR-9 plays an important role in proliferation and angiogenesis in VECs.
PMID- 28418725
TI - MEDEX 2015: Heart Rate Variability Predicts Development of Acute Mountain
Sickness.
AB - : Sutherland, Angus, Joseph Freer, Laura Evans, Alberto Dolci, Matteo Crotti, and
Jamie Hugo Macdonald. MEDEX 2015: Heart rate variability predicts development of
acute mountain sickness. High Alt Med Biol. 18: 199-208, 2017. AIMS: Acute
mountain sickness (AMS) develops when the body fails to acclimatize to
atmospheric changes at altitude. Preascent prediction of susceptibility to AMS
would be a useful tool to prevent subsequent harm. Changes to peripheral oxygen
saturation (SpO2) on hypoxic exposure have previously been shown to be of poor
predictive value. Heart rate variability (HRV) has shown promise in the early
prediction of AMS, but its use pre-expedition has not previously been
investigated. We aimed to determine whether pre- and intraexpedition HRV
assessment could predict susceptibility to AMS at high altitude with better
diagnostic accuracy than SpO2. METHODS: Forty-four healthy volunteers undertook
an expedition in the Nepali Himalaya to >5000 m. SpO2 and HRV parameters were
recorded at rest in normoxia and in a normobaric hypoxic chamber before the
expedition. On the expedition HRV parameters and SpO2 were collected again at
3841 m. A daily Lake Louise Score was obtained to assess AMS symptomology.
RESULTS: Low frequency/high frequency (LF/HF) ratio in normoxia (cutpoint <=2.28
a.u.) and LF following 15 minutes of exposure to normobaric hypoxia had moderate
(area under the curve >=0.8) diagnostic accuracy. LF/HF ratio in normoxia had the
highest sensitivity (85%) and specificity (88%) for predicting AMS on subsequent
ascent to altitude. In contrast, pre-expedition SpO2 measurements had poor (area
under the curve <0.7) diagnostic accuracy and inferior sensitivity and
specificity. CONCLUSIONS: Pre-ascent measurement of HRV in normoxia was found to
be of better diagnostic accuracy for AMS prediction than all measures of HRV in
hypoxia, and better than peripheral oxygen saturation monitoring.
PMID- 28418726
TI - U50: A New Metric for Measuring Assembly Output Based on Non-Overlapping, Target
Specific Contigs.
AB - Advances in next-generation sequencing technologies enable routine genome
sequencing, generating millions of short reads. A crucial step for full genome
analysis is the de novo assembly, and currently, performance of different
assembly methods is measured by a metric called N50. However, the N50 value can
produce skewed, inaccurate results when complex data are analyzed, especially for
viral and microbial datasets. To provide a better assessment of assembly output,
we developed a new metric called U50. The U50 identifies unique, target-specific
contigs by using a reference genome as baseline, aiming at circumventing some
limitations that are inherent to the N50 metric. Specifically, the U50 program
removes overlapping sequence of multiple contigs by utilizing a mask array, so
the performance of the assembly is only measured by unique contigs. We compared
simulated and real datasets by using U50 and N50, and our results demonstrated
that U50 has the following advantages over N50: (1) reducing erroneously large
N50 values due to a poor assembly, (2) eliminating overinflated N50 values caused
by large measurements from overlapping contigs, (3) eliminating diminished N50
values caused by an abundance of small contigs, and (4) allowing comparisons
across different platforms or samples based on the new percentage-based metric
UG50%. The use of the U50 metric allows for a more accurate measure of assembly
performance by analyzing only the unique, non-overlapping contigs. In addition,
most viral and microbial sequencing have high background noise (i.e., host and
other non-targets), which contributes to having a skewed, misrepresented N50
value-this is corrected by U50. Also, the UG50% can be used to compare assembly
results from different samples or studies, the cross-comparisons of which cannot
be performed with N50.
PMID- 28418727
TI - Poor Sleep Is Associated With Greater Marital Aggression: The Role of Self
Control.
AB - BACKGROUND/OBJECTIVE: Although sleep problems are linked to relationship
difficulties, the mechanisms involved have not been empirically demonstrated. The
present study considers self-control as such a mechanism. PARTICIPANTS: Data were
collected from 342 predominantly white, middle-class, married adults. METHOD:
Participants completed online questionnaires about sleep, marital aggression, and
self-control, and a virtual voodoo doll task. RESULTS AND CONCLUSIONS: Sleep
problems were associated with higher levels of aggression on all measures, and
lower self-control mediated these associations. Associations did not depend on
participant gender, presence of children in the home, income, or length of
marriage.
PMID- 28418728
TI - Prevalence and Predictors of Food Insecurity among People Living with HIV
Enrolled in Antiretroviral Therapy and Livelihood Programs in Two Rural Zambian
Hospitals.
AB - The objective of this study was to examine the prevalence and predictors of food
insecurity among people living with HIV (PLHIV) in two rural communities in
Zambia. A cross-sectional sample of 101 PLHIV was surveyed using the Household
Food Insecurity Access Scale. In multivariable linear regression models, income,
household possessions, and perceived coping strategies were significantly
associated with decreased food insecurity. Debt and perceived mental distress
were significantly associated with increased food insecurity. Programs that
tackle economic disadvantage and its adverse effect on stress may be an
appropriate strategy to improve food security of PLHIV in low-resource
communities.
PMID- 28418729
TI - Relationship of cognitive functions and gross motor abilities in children with
spastic diplegic cerebral palsy.
AB - Spastic diplegic cerebral palsy can be accompanied by a myriad of symptoms
affecting other body systems including cognitive dysfunction. The purpose of this
study was to determine whether a relationship exists between cognitive functions
in the form of selective attention and figural memory domains with standing and
walking motor abilities in children with diplegic cerebral palsy. The research
design was a correlational study. Tasks assessing cognitive function and gross
motor abilities were carried out with a sample of 50 children. The data
demonstrated the presence of correlation between selective attention and figural
memory domains of cognitive function with standing, walking running, and jumping
subscales of the Gross Motor Function Measure (GMFM) scale at different ages, and
this correlation was significant between selective attention domain and gross
motor abilities. The outcome measurements of the current study provide original
evidence based on the necessity of including cognitive and physical impairments
in the examination and evaluation of children with diplegic cerebral palsy in
research and clinical settings.
PMID- 28418730
TI - Patient Inputs for Mobile Health Systems for Type 1 Diabetes Care.
PMID- 28418731
TI - Why Do Some Concentrated Insulins Maintain Their
Pharmacokinetics/Pharmacodynamics Profile?
PMID- 28418732
TI - Insulin Infusion Sets and Continuous Glucose Monitoring Sensors: Where the
Artificial Pancreas Meets the Patient.
PMID- 28418733
TI - Feasibility of SPECT-CT Imaging to Study the Pharmacokinetics of Antisense
Oligonucleotides in a Mouse Model of Duchenne Muscular Dystrophy.
AB - Antisense oligonucleotides (AONs) are promising candidates for treatment of
Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in
premature death. However, more knowledge on the pharmacokinetics of new AON drug
candidates is desired for effective application in the clinic. We assessed the
feasibility of using noninvasive single-photon emission computed tomography
computed tomography (SPECT-CT) imaging to determine AON pharmacokinetics in vivo.
To this end, a 2'-O-methyl phosphorothioate AON was radiolabeled with 123I or
111In, and administered to mdx mice, a rodent model of DMD. SPECT-CT imaging was
performed to determine AON tissue levels, and the results were compared to data
obtained with invasive analysis methods (scintillation counting and a ligation
hybridization assay). We found that SPECT-CT data obtained with 123I-AON and
111In-AON were qualitatively comparable to data derived from invasive analytical
methods, confirming the feasibility of using SPECT-CT analysis to study AON
pharmacokinetics. Notably, also AON uptake in skeletal muscle, the target tissue
in DMD, could be readily quantified using SPECT-CT imaging, which was considered
a particular challenge in mice, due to their small size. In conclusion, our
results demonstrate that SPECT-CT imaging allows for noninvasive characterization
of biodistribution and pharmacokinetics of AONs, thereby enabling quantitative
comparisons between different radiolabeled AON drug candidates and qualitative
conclusions about the corresponding unmodified parent AONs. This technology may
contribute to improved (pre)clinical drug development, leading to drug candidates
with optimized characteristics in vivo.
PMID- 28418734
TI - Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery.
AB - Bunyaviridae family is the largest and most diverse family of RNA viruses. It has
more than 350 members divided into five genera: Orthobunyavirus, Phlebovirus,
Nairovirus, Hantavirus, and Tospovirus. They are present in the five continents,
causing recurrent epidemics, epizootics, and considerable agricultural loss. The
genome of bunyaviruses is divided into three segments of negative single-stranded
RNA according to their relative size: L (Large), M (Medium) and S (Small)
segment. Bunyaviridae RNA-dependent RNA polymerase (RdRp) is encoded by the L
segment, and is in charge of the replication and transcription of the viral RNA
in the cytoplasm of the infected cell. Viral RdRps share a characteristic right
hand-like structure with three subdomains: finger, palm, and thumb subdomains
that define the formation of the catalytic cavity. In addition to the N-terminal
endonuclease domain, eight conserved motifs (A-H) have been identified in the
RdRp of Bunyaviridae. In this review, we have summarized the recent insights from
the structural and functional studies of RdRp to understand the roles of
different motifs shared by RdRps, the mechanism of viral RNA replication, genome
segment packaging by the nucleoprotein, cap-snatching, mRNA transcription, and
other RNA mechanisms of bunyaviruses.
PMID- 28418735
TI - Polymorphisms of COMT (c.649G>A), MAO-A (c.1460C>T), NET (c.1287G>A) Genes and
the Level of Catecholamines, Serotonin in Patients with Parkinson's Disease.
AB - The purpose of this study was to determine the concentration of plasma
norepinephrine (NE), epinephrine (E), and serotonin (5-HT) in two collections,
after a 30-min supine (I) and 5-min upright position (II), and polymorphisms of
genes, COMT (c.649G>A), MAO-A (c.1460C>T), and NET (c.1287G>A), in patients with
Parkinson's disease (PD) and other degenerative parkinsonism and controls. The
study was performed in 49 PD patients, 19 parkinsonism patients, and 48 controls.
The level of NE, E, and 5-HT was determined by HPLC/EC. PCR-RFLP was conducted to
analyze the COMT, MAO-A, and NET polymorphisms. Genotypes of COMT, MAO-A, and NET
genes occurred with different frequencies in patients with movement disorders and
controls. NET AA occurred 4.8 times more frequently in patients with parkinsonism
than in PD (p < 0.05). COMT AA genotype was associated with increased E levels [E
(I) p < 0.01, E (II) p < 0.05] in PD compared to controls. Patients with
parkinsonism with MAO-A TT genotype have a significantly higher level of 5-HT [5
HT (II), p < 0.05] compared to controls. Moreover, PD patients with NET GA
genotype have the lowest level of NE (p < 0.05) compared to controls. It appears
that COMT, MAO-A, and NET polymorphisms and levels of NE, E, and 5-HT are
involved in pathogenesis of PD.
PMID- 28418736
TI - Curricular Time, Patient Exposure, and Comfort Caring for Lesbian, Gay, Bisexual,
and Transgender Patients Among Recent Medical Graduates.
PMID- 28418737
TI - Public Health Emergency Response in Taiwan.
AB - In recent years, growth of international travel and trade, as well as climate
change, has resulted in the frequent emergence and reemergence of infectious
diseases such as Ebola, Zika, and MERS. In 2016, Taiwan used the Joint External
Evaluation (JEE) tool to evaluate its public health emergency response capacities
and understand important areas for improvement. This article presents Taiwan's
disaster and public health emergency response organizational structure, real-time
integrated information, response processes, and command center structure. After
reviewing the results of the JEE tool and drawing lessons from emergency response
efforts in the United States, we provide 3 recommendations that may enhance
Taiwan's public health emergency response capacities: establish common principles
for disaster response regardless of which agency is in charge, standardize
operation procedures, and perform regular training that includes nongovernmental
organizations and a range of government departments.
PMID- 28418738
TI - Real-Time Surveillance of Infectious Diseases: Taiwan's Experience.
AB - Integration of multiple surveillance systems advances early warning and supports
better decision making during infectious disease events. Taiwan has a
comprehensive network of laboratory, epidemiologic, and early warning
surveillance systems with nationwide representation. Hospitals and clinical
laboratories have deployed automatic reporting mechanisms since 2014 and have
effectively improved timeliness of infectious disease and laboratory data
reporting. In June 2016, the capacity of real-time surveillance in Taiwan was
externally assessed and was found to have a demonstrated and sustainable
capability. We describe Taiwan's disease surveillance system and use surveillance
efforts for influenza and Zika virus as examples of surveillance capability.
Timely and integrated influenza information showed a higher level and extended
pattern of influenza activity during the 2015-16 season, which ensured prompt
information dissemination and the coordination of response operations. Taiwan
also has well-developed disease detection systems and was the first country to
report imported cases of Zika virus from Miami Beach and Singapore. This
illustrates a high level of awareness and willingness among health workers to
report emerging infectious diseases, and highlights the robust and sensitive
nature of Taiwan's surveillance system. These 2 examples demonstrate the
flexibility of the surveillance systems in Taiwan to adapt to emerging infectious
diseases and major communicable diseases. Through participation in the GHSA,
Taiwan can more actively collaborate with national counterparts and use its
expertise to strengthen global and regional surveillance capacity in the Asia
Pacific and in Southeast Asia, in order to advance a world safe and secure from
infectious disease.
PMID- 28418740
TI - Immunoassays for Field Screening of Bacillus anthracis and Ricin.
PMID- 28418739
TI - The Joint External Evaluation of Taiwan: The External Evaluators' Perspective.
AB - A team of experts from the Johns Hopkins Center for Health Security conducted an
independent external assessment of Taiwan's capabilities under the International
Health Regulations 2005 (IHR), using the IHR Joint External Evaluation (JEE) tool
adopted by the World Health Organization and the Global Health Security Agenda.
In this article we describe the methods and process of the assessment, identify
lessons learned, and make recommendations for the government of Taiwan, the JEE
process, and the JEE tool.
PMID- 28418741
TI - Implementation of the IHR Joint External Evaluation: Taiwan's Experiences.
AB - In February 2016, the World Health Organization developed the Joint External
Evaluation (JEE) tool to independently assess country capacity to prevent,
detect, and respond to public health threats as part of the International Health
Regulations (IHR) (2005) monitoring and evaluation framework. In light of this,
the Taiwan government actively engaged at least 19 government agencies or
institutions and voluntarily implemented the JEE. An External Assessment Team
consisting of 6 US subject matter experts conducted the external evaluation,
including site visits, from June 21 to July 1, 2016. The results, published on
October 18, 2016, are useful and will be translated into actions and change in
the system. Based on Taiwan's experiences, early stakeholder engagement and an
experts' pre-JEE pilot visit would contribute to a successful JEE process.
PMID- 28418743
TI - Stockpile Model of Personal Protective Equipment in Taiwan.
AB - The Taiwan Centers for Disease Control (Taiwan CDC) has established a 3-tier
personal protective equipment (PPE) stockpiling framework that could maintain a
minimum stockpile for the surge demand of PPE in the early stage of a pandemic.
However, PPE stockpiling efforts must contend with increasing storage fees and
expiration problems. In 2011, the Taiwan CDC initiated a stockpile replacement
model in order to optimize the PPE stockpiling efficiency, ensure a minimum
stockpile, use the government's limited funds more effectively, and achieve the
goal of sustainable management. This stockpile replacement model employs a first
in-first-out principle in which the oldest stock in the central government
stockpile is regularly replaced and replenished with the same amount of new and
qualified products, ensuring the availability and maintenance of the minimum
stockpiles. In addition, a joint electronic procurement platform has been
established for merchandising the replaced PPE to local health authorities and
medical and other institutions for their routine or epidemic use. In this
article, we describe the PPE stockpile model in Taiwan, including the 3-tier
stockpiling framework, the operational model, the components of the replacement
system, implementation outcomes, epidemic supports, and the challenges and
prospects of this model.
PMID- 28418742
TI - Taiwan's Public Health National Laboratory System: Success in Influenza Diagnosis
and Surveillance.
AB - Taiwan's National Laboratory System is one of the action packages of the Global
Health Security Agenda, which was launched by the World Health Organization (WHO)
to promote health security as an international priority and to encourage progress
toward full implementation of the WHO International Health Regulations (IHR)
2005. The mission of each national laboratory system is to conduct real-time
biosurveillance and effective laboratory-based diagnostics, as measured by a
nationwide laboratory system able to reliably conduct diagnoses on specimens
transported properly to designated laboratories from at least 80% of the regions
in the country. In Taiwan, the national laboratory system for public health is
well-established and coordinated by the Taiwan Centers for Disease Control (CDC),
which is the government authority in charge of infectious disease prevention and
intervention. Through the national laboratory system, Taiwan CDC effectively
detects and characterizes pathogens that cause communicable diseases across the
entire country, including both known and novel threats, and also conducts
epidemiologic analyses of infectious diseases. In this article, we describe the
national laboratory system for public health in Taiwan. We provide additional
information on the national influenza laboratory surveillance network to
demonstrate how our national laboratory systems work in practice, including
descriptions of long-term seasonal influenza characterization and successful
experiences identifying novel H7N9 and H6N1 influenza viruses.
PMID- 28418744
TI - Taiwan's Travel and Border Health Measures in Response to Zika.
AB - Zika virus has recently emerged as a worldwide public health concern. Travel and
border health measures stand as one of the main strategies and frontline defenses
in responding to international epidemics. As of October 31, 2016, Taiwan has
reported 13 imported cases, 5 of which were detected through routine entry
screening and active monitoring at international airports. This article shares
Taiwan's disease surveillance activities at designated points of entry and travel
and border health measures in response to Zika. The Taiwan government
collaborates with its tourism industry to disseminate information about
precautionary measures and encourages tour guides to report suspected individuals
or events to activate early response measures. Taiwan also engages in vector
control activities at points of entry, including targeting aircraft from
countries where vector-borne diseases are endemic, implementing mosquito sweep
measures, and collecting vector surveillance data. In future emerging and
reemerging disease events, entry surveillance at designated points of entry may
enable early detection of diseases of international origin and more rapid
activation of public health preparedness activities and international
collaboration. Taiwan will continue to maximize border and travel health measures
in compliance with IHR (2005) requirements, which rely on continued risk
assessment, practical implementation activities, and engagement with all
stakeholders.
PMID- 28418745
TI - Taiwan's Experience in Hospital Preparedness and Response for Emerging Infectious
Diseases.
AB - The Communicable Disease Control Medical Network (CDCMN), established in 2003
after the SARS outbreak in Taiwan, has undergone several phases of modification
in structure and activation. The main organizing principles of the CDCMN are
centralized isolation of patients with severe highly infectious diseases and
centralization of medical resources, as well as a network of designated regional
hospitals like those in other countries. The CDCMN is made up of a command
system, responding hospitals, and supporting hospitals. It was tested and
activated in response to the H1N1 influenza pandemic in 2009-10 and the Ebola
outbreak in West Africa in 2014-2016, and it demonstrated high-level functioning
and robust capacity. In this article, the history, structure, and operation of
the CDCMN is introduced globally for the first time, and the advantages and
challenges of this system are discussed. The Taiwanese experience shows an
example of a collaboration between the public health system and the medical
system that may help other public health authorities plan management and hospital
preparedness for highly infectious diseases.
PMID- 28418747
TI - Promoting Health Security: Potential, Role, and Future Directions of a Medical
University.
PMID- 28418746
TI - Risk and Outbreak Communication: Lessons from Taiwan's Experiences in the Post
SARS Era.
AB - In addition to the impact of a disease itself, public reaction could be
considered another outbreak to be controlled during an epidemic. Taiwan's
experience with SARS in 2003 highlighted the critical role played by the media
during crisis communication. After the SARS outbreak, Taiwan's Centers for
Disease Control (Taiwan CDC) followed the WHO outbreak communication guidelines
on trust, early announcements, transparency, informing the public, and planning,
in order to reform its risk communication systems. This article describes the
risk communication framework in Taiwan, which has been used to respond to the
2009-2016 influenza epidemics, Ebola in West Africa (2014-16), and MERS-CoV in
South Korea (2015) during the post-SARS era. Many communication strategies,
ranging from traditional media to social and new media, have been implemented to
improve transparency in public communication and promote civic engagement. Taiwan
CDC will continue to maintain the strengths of its risk communication systems and
resolve challenges as they emerge through active evaluation and monitoring of
public opinion to advance Taiwan's capacity in outbreak communication and
control. Moreover, Taiwan CDC will continue to implement the IHR (2005) and to
promote a global community working together to fight shared risks and to reach
the goal of "One World, One Health."
PMID- 28418749
TI - An improved technique for obtaining well-spread metaphases from plants with
numerous large chromosomes.
AB - Preparations that contain well-spread metaphase chromosomes are critical for
plant cytogenetic analyses including chromosome counts, banding procedures, in
situ hybridization, karyotyping and construction of ideograms. Chromosome
spreading is difficult for plants with large and numerous chromosomes. We report
here a technique for obtaining cytoplasm-free, well-spread metaphases from two
Amaryllidaceae species: Sprekelia formosissima (2n = 120) and Hymenocallis
howardii (2n = 96). The technique has three main steps: 1) pretreatment to cause
chromosome condensation, 2) dripping onto tilted slides coated with a thin layer
of pure acetic acid and 3) application of steam and acetic acid to produce
cytoplasmic hydrolysis, which spreads the chromosomes.
PMID- 28418750
TI - Comparing Asian American Women's Knowledge, Self-Efficacy, and Perceived Risk of
Heart Attack to Other Racial and Ethnic Groups: The mPED Trial.
AB - OBJECTIVE: The aim of the study was to compare knowledge and awareness of heart
attacks/heart disease and perceived risk for future heart attack in Asian/Pacific
Islander women, compared to other racial and ethnic groups. MATERIALS AND
METHODS: In this cross-sectional study, 318 women enrolled in a mobile phone
based physical activity education trial were analyzed. Heart attack knowledge,
self-efficacy for recognizing and responding to heart attack symptoms, and
perceived risk for a future heart attack were measured. Analyses were conducted
using logistic, proportional odds, and linear regression models, depending on the
outcome and adjusting for age. Pairwise differences between Asian/Pacific
Islanders and the other four groups were assessed using a Bonferroni correction
(p < 0.0125). RESULTS: Asian/Pacific Islander women had significantly lower total
scores for knowledge of heart attack and self-efficacy for heart attack
recognition and care seeking behavior compared to the Caucasian women (p = 0.001
and p = 0.002, respectively). However, perceived risk did not differ among the
groups. Forty-six percent of the Asian American women, compared to 25% of
Caucasian women, falsely believed "breast cancer is the number one cause of death
for women (p = 0.002)." In addition, Asian/Pacific Islander women were less
likely to report "arm pain, numbness, tingling, or radiating" as one of the heart
attack symptoms compared to the Caucasian and the multiracial group (34%, 63% [p
< 0.001], and 66% [p = 0.004], respectively). CONCLUSIONS: These findings
highlight the urgent need to develop effective, tailored campaigns to close the
knowledge gap between Asian/Pacific Islander women and Caucasian women.
PMID- 28418751
TI - Influence of Exergaming on the Perception of Cancer-Related Fatigue.
AB - OBJECTIVE: Exercise is recommended for cancer patients to reduce fatigue and
improve quality of life. This study's aim is to evaluate the influence of an
exergaming protocol on cancer-related fatigue, muscle fatigue, and muscle
strength in cancer patients. MATERIALS AND METHODS: We conducted a quasi
experimental control study using exergaming in all groups through an Xbox360
KinectTM console, two to three times per week, for 20 sessions. Three groups were
created: cancer patients in chemotherapy and/or radiotherapy group (CRG; n:15),
cancer patients after chemotherapy and/or radiotherapy (CAG; n:15), and a control
group (CG; n:15). They were assessed for cancer-related fatigue using the fatigue
subscale of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT
F) questionnaire. To assess dorsiflexor and plantar flexor muscle functioning, we
used median frequency (MDF) of the surface electromyography and muscle strength
using a dynamometer. The assessments were performed preintervention (EV0), after
10 sessions (EV1), and after 20 sessions (EV2). RESULTS: With an exergaming
protocol, CRG and CAG showed a reduction in related fatigue compared with CG (P <
0.01). The CRG group saw an increase in maximal voluntary isometric contraction
in right plantar flexor muscles and dorsiflexor muscles, as well as an increase
in the MDF of both medial gastrocnemius muscles and the left tibialis anterior
muscle of the CAG. For other analyses done, the differences were observed during
exergaming. CONCLUSIONS: Exergaming demonstrated efficacy in reducing cancer
patients' fatigue, including muscle fatigue, and increasing muscle strength in
patients' legs.
PMID- 28418752
TI - A Pilot Study of the Attractive Features of Active Videogames Among Chinese
Primary School Children.
AB - OBJECTIVE: The present study (1) explored the attractive features that affect
Chinese primary school children's preferences of active videogames (AVGs) and (2)
contrasted these findings with those in the Western literature. PARTICIPANTS AND
METHODS: A total of 22 Chinese primary school children were recruited and
interviewed. Four AVGs (Wii "Boxing," "Wii FitTM Plus Obstacle Run"; "EyeToy
Knockout", "EyeToy Keep ups") from two commercial consoles (Nintendo(r) WiiTM and
Sony PlayStation(r) 2 "EyeToy(r)") were employed. Participants used four selected
AVGs for 3 minutes each. After each play period, children (1) described the
strengths and weaknesses of each game as well as rated the attractive features of
each game based on a 16-item questionnaire and (2) rated up to 5 items that were
most influential regarding their AVG preferences. RESULTS: Participants indicated
that control was the most significant feature, followed by feedback, goal, and
graphics. The top five rated features imply that the perception of competence was
the most appealing aspect and expected outcome of Chinese children who play AVGs.
CONCLUSIONS: Compared with the Western findings regarding attractive AVG
features, the present study found certain similarities as well as significant
differences among Chinese AVG players. Based on the present study, control,
feedback, goal, and graphics are the most significant features that attract
Chinese children to play AVGs. Physical exertion, social interaction,
competition, and learning outcomes, which are valued according to Western
studies, were not mentioned as significant features by Chinese children. These
findings demonstrate a need to investigate the effect of cultural background in
AVG study design.
PMID- 28418753
TI - Intraosseous Pressure Monitoring in Healthy Volunteers.
AB - STUDY OBJECTIVE: Invasively monitoring blood pressure through the IO device has
not been thoroughly demonstrated. This study attempted to establish baseline
values of IO pressure in a healthy human population. METHODS: This was a
prospective, healthy volunteer, observational study. Participants had two IO
devices placed (humerus and tibia), and participant IO pressures, vital signs,
and pain scores were monitored for up to 60 minutes. Participants were contacted
at 24-hours and 7 days post-testing to assess for adverse events. Summary
statistics were calculated for systolic, diastolic, and mean humeral and tibial
IO pressure. The ratio of IO to non-invasive blood pressure was calculated, and
Bland Altman plots were created. The slope (linear) of the mean humeral and the
tibial IO pressures were also calculated. RESULTS: Fifteen subjects were enrolled
between April and July 2015. Fourteen of 15 humeral IOs were placed successfully
(93.3%) and all 15 of the tibial IOs were placed successfully. Mean tibial
systolic, diastolic, and mean IO pressure were 55.8 +/- 27.9, 49.3 +/- 27.1, and
48.4 +/- 29.4 mm Hg, respectively. Humeral systolic, diastolic, and mean IO
pressure were 32.9 +/- 16.0, 27.4 +/- 15.2, and 24.5 +/- 14.3 mm Hg. The mean
tibial IO pressure was 52.5% +/- 32.0% of external cuff pressure ratio. The mean
humeral IO pressure was 26.5% +/- 15.2% of the external mean blood pressure. The
Bland Altman plots showed an inconsistent relationship between the systolic and
diastolic cuff pressure and the IO pressures. We observed a 1% per minute
decrease in IO pressure from the initial placement until the final reading.
CONCLUSIONS: Intraosseous pressure readings can be obtained in healthy human
volunteers. However, absolute IOP values were not consistent between subjects.
Future research may determine how IO pressure can be used to guide therapy in ill
and injured patients.
PMID- 28418754
TI - Evaluating the Effect of Virtual Reality Temporal Bone Simulation on
Mastoidectomy Performance: A Meta-analysis.
AB - Background The increasing prevalence of virtual reality simulation in temporal
bone surgery warrants an investigation to assess training effectiveness.
Objectives To determine if temporal bone simulator use improves mastoidectomy
performance. Data Sources Ovid Medline, Embase, and PubMed databases were
systematically searched per the PRISMA guidelines. Review Methods Inclusion
criteria were peer-reviewed publications that utilized quantitative data of
mastoidectomy performance following the use of a temporal bone simulator. The
search was restricted to human studies published in English. Studies were
excluded if they were in non-peer-reviewed format, were descriptive in nature, or
failed to provide surgical performance outcomes. Meta-analysis calculations were
then performed. Results A meta-analysis based on the random-effects model
revealed an improvement in overall mastoidectomy performance following training
on the temporal bone simulator. A standardized mean difference of 0.87 (95% CI,
0.38-1.35) was generated in the setting of a heterogeneous study population ( I2
= 64.3%, P < .006). Conclusion In the context of a diverse population of virtual
reality simulation temporal bone surgery studies, meta-analysis calculations
demonstrate an improvement in trainee mastoidectomy performance with virtual
simulation training.
PMID- 28418755
TI - Recommendations for Adopting the International Code of Marketing of Breast-milk
Substitutes Into U.S. Policy.
AB - In 1981, the World Health Organization adopted the International Code of
Marketing of Breast-milk Substitutes ( International Code), with subsequent
resolutions adopted since then. The International Code contributes to the safe
and adequate provision of nutrition for infants by protecting and promoting
breastfeeding and ensuring that human milk substitutes, when necessary, are used
properly through adequate information and appropriate marketing and distribution.
Despite the World Health Organization recommendations for all member nations to
implement the International Code in its entirety, the United States has yet to
take action to translate it into any national measures. In 2012, only 22.3% of
infants in the United States met the American Academy of Pediatrics
recommendation of at least 6 months of exclusive breastfeeding. Countries
adopting legislation reflecting the provisions of the International Code have
seen increases in breastfeeding rates. This article discusses recommendations for
translating the International Code into U.S. policy. Adopting legislation that
implements, monitors, and enforces the International Code in its entirety has the
potential to contribute to increased rates of breastfeeding in the United States,
which can lead to improved health outcomes in both infants and breastfeeding
mothers.
PMID- 28418757
TI - Visual Circuits for Direction Selectivity.
AB - Images projected onto the retina of an animal eye are rarely still. Instead, they
usually contain motion signals originating either from moving objects or from
retinal slip caused by self-motion. Accordingly, motion signals tell the animal
in which direction a predator, prey, or the animal itself is moving. At the
neural level, visual motion detection has been proposed to extract directional
information by a delay-and-compare mechanism, representing a classic example of
neural computation. Neurons responding selectively to motion in one but not in
the other direction have been identified in many systems, most prominently in the
mammalian retina and the fly optic lobe. Technological advances have now allowed
researchers to characterize these neurons' upstream circuits in exquisite detail.
Focusing on these upstream circuits, we review and compare recent progress in
understanding the mechanisms that generate direction selectivity in the early
visual system of mammals and flies.
PMID- 28418756
TI - Cultured microbes represent a substantial fraction of the human and mouse gut
microbiota.
AB - During the last 15 years, molecular techniques have been preferred over culture
based approaches for the study of mammalian gut microbiota, i.e. the communities
of microorganisms dwelling in the intestine of mammals. The main reason is the
belief that the majority of gut bacteria, especially strict anaerobes, escape
cultivation. Despite numerous such statements in publications, the literature
does not provide a clear overview on the subject. In the present manuscript, we
highlight recent work on the cultivation of bacteria from the intestine of
mammals, review the literature and provide novel data pertaining to cultured
fractions of mammalian gut microbiota. These data show that, despite marked inter
sample variations, 35 to 65% of molecular species detected by sequencing have
representative strains in culture.
PMID- 28418758
TI - Inhaled Heparin: Therapeutic Efficacy and Recent Formulations.
AB - Heparin is well known for its anticoagulant and anti-inflammatory properties.
Inhaled heparin regimens are increasingly being used to manage lung disease. It
has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis,
as well as bronchial asthma and asthma-induced airway hypersensitivity. Several
preclinical studies attained some useful effects of heparin-administered,
parenterally and through inhalation, treatment of lung disease. Besides, recent
clinical trials suggest that inhaled heparin for lung diseases is beneficial and
safe, but such data remain to be limited. In 2005, the orphan designation was
granted by the European Commission for heparin sodium (inhalation use) for the
treatment of cystic fibrosis. The positive results of heparin in the pulmonary
route necessitate a focus on the preparation and evaluation of heparin in
advanced drug delivery systems, namely nano/microparticles and liposomes. Through
this pulmonary delivery, heparin is protected from enzymatic degradation within
the airway. Heparin is thus passively targeted into the lungs, and long-lasting
localized treatment is achieved. On the other hand, these systems have
encountered several problems as follows: (1) polymers, such as poly-L-lactide
glycolic acid, poly (lactic acid), and chitosan, used to prepare heparin-loaded
microparticle/nanoparticle (MP/NP) systems have not been granted approval for
lung application by the FDA and (2) liposomal and NP formulation stability is the
main problem of formulation design. We propose that additional in vitro and in
vivo research is necessary to assess the clinical applicability of this treatment
strategy. The present article discusses heparin treatments for lung diseases and
the use of heparin and/or heparin-loaded drugs in advanced delivery systems
through the pulmonary route.
PMID- 28418759
TI - Virulence profile: Swaine L. Chen.
PMID- 28418760
TI - Aromatic dipeptide Trp-Ala can be transported by Arabidopsis peptide transporters
AtPTR1 and AtPTR5.
AB - Dipeptides with an aromatic residue at the N-terminal position induced lower
inward currents or blocked leak currents in Xenopus oocytes expressing the proton
coupled peptide transporter AtPTR1 or AtPTR5 of Arabidopsis thaliana compared
with dipeptides with an aromatic residue at the C-terminal position. Here, AtPTR1
and AtPTR5 were expressed in a yeast mutant of peptide transporter (ptr2) with
tryptophan auxotrophy. Growth assays showed that Trp-Ala could be transported by
both AtPTR1 and AtPTR5 as efficiently as Ala-Trp. Our data suggested that the
previous finding in Xenopus oocytes might be an artifact of heterologous
expression, and that AtPTR1 and AtPTR5 expressed in yeast could transport
dipeptides with an aromatic residue at the N-terminal position.
PMID- 28418761
TI - Economic Evaluation of a Hospital-Based Palliative Care Program.
AB - PURPOSE: Establish costs of an inpatient palliative care unit (PCU) and conduct a
threshold analysis to estimate the maximum possible costs for the PCU to be
considered cost effective. METHODS: We used a hospital perspective to determine
costs on the basis of claims from administrative data from Johns Hopkins PCU
between March 2013 and March 2014. Using existing literature, we estimated the
number of quality-adjusted life years (QALYs) that the PCU could generate. We
conducted a threshold analysis to assess the maximum costs for the PCU to be
considered cost effective, incorporating willingness to pay ($180,000 per QALY).
Three types of costs were considered, which included variable costs alone,
contribution margin (ie, revenue minus variable costs), and PCU cost savings
compared with usual care (from a separate publication). RESULTS: The data showed
that there were 153 patient encounters (PEs), variable costs of $1,050,031
($1,343 per PE per day), a contribution margin of $318,413 ($407 per PE per day),
and savings compared with usual care of $353,645 ($452 savings per PE per day).
On the basis of the literature, the program could generate 3.11 QALYs from PEs
(0.05 QALY) and caregivers (3.06 QALYs). The threshold analysis determined that
the maximum variable cost required to be cost effective was $559,800 (an
additional $716 per PE per day could be spent). CONCLUSION: According to variable
costs, the PCU was not cost effective; however, when considering savings of the
PCU compared with usual care, the PCU was cost saving. The contribution margin
showed that the PCU was cost saving. This study supports efforts to expand PCUs,
which enhance care for patients and their caregivers and can generate hospital
savings. Future research should prospectively explore the cost utility of PCUs.
PMID- 28418762
TI - Challenges Persist Under Americans With Disabilities Act Amendments Act: How Can
Oncology Providers Help?
AB - PURPOSE: To determine whether the Amendments to the hallmark Americans with
Disabilities Act (ADA; effective January 2009), which provide increased access to
the antidiscrimination laws for many with chronic illness, are related to changes
in workplace discrimination allegations in individuals with a history of cancer.
METHODS: Information collected by the Equal Employment Opportunities Commission
was used to compare allegations of discrimination and their merit before (2001 to
2008) and after (2009 to 2011) implementation of the Amendments Act. RESULTS:
Allegations related to terms of employment (eg, promotions, wages) were more
likely to be filed (odds ratio [OR], 1.34; 95% CI, 1.11 to 1.61) and determined
to have merit (OR, 1.35; 95% CI, 1.03 to 1.77) after implementation of the
Amendments Act. Allegations related to workplace relations (eg, harassment,
discipline, discharge) were also more likely to be filed post Amendments Act (OR,
1.48; 95% CI, 1.23 to 1.78), although the merit of this complaint remained
stable. Filing of all other allegations of discrimination (ie, hiring, reasonable
accommodation, and termination) and their merit remained unchanged post
Amendments Act. CONCLUSION: Despite the implementation of the Amendments Act,
discrimination allegations in those with a history of cancer persisted or in
certain areas increased. Although prevention of workplace discrimination rests
primarily with employers, the oncology care team is uniquely qualified to provide
information related to residual symptoms and function that can facilitate more
personalized solutions to workplace discrimination, such as successful workplace
accommodations. Information is provided that can assist the oncology team in
their efforts to improve work outcomes.
PMID- 28418763
TI - Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma:
Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11
Trials.
AB - Purpose Combined-modality treatment is widely considered the standard of care in
early-stage Hodgkin lymphoma (HL), and treatment intensity has been reduced over
the last years. Long-term follow-up is important to judge both efficacy and
safety of the different therapies used. Patients and Methods We analyzed updated
follow-up data on 4,276 patients treated within the German Hodgkin Study Group
trials HD7 and HD10 for early-stage favorable HL and HD8 and HD11 for early-stage
unfavorable HL between 1993 and 2003. Results In HD7 (N = 627; median follow-up,
120 months), combined-modality treatment was superior to extended-field
radiotherapy (RT), with 15-year progression-free survival (PFS) of 73% versus 52%
(hazard ratio [HR], 0.5; 95% CI, 0.3 to 0.6; P < .001), without differences in
overall survival (OS). In HD10 (N = 1,190; median follow-up, 98 months),
noninferiority of two cycles of doxorubicin, bleomycin, vinblastine, dacarbazine
(ABVD) plus 20 Gy involved-field (IF)-RT to more intensive four cycles of ABVD
plus 30 Gy IF-RT was confirmed with 10-year PFS of 87% each (HR, 1.0; 95%, 0.6 to
1.5) and OS of 94% each (HR, 0.9; 95% CI, 0.5 to 1.6), respectively. In both
trials, no differences in second neoplasias were observed. In HD8 (N = 1,064;
median follow-up, 153 months), noninferiority of involved-field RT to extended
field RT regarding PFS was confirmed (HR, 1.0; 95% CI, 0.8 to 1.2). In HD11 (N =
1,395; median follow-up, 106 months), superiority of bleomycin, etoposide,
doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at
baseline over ABVD was not observed. After BEACOPPbaseline, 20 Gy IF-RT was
noninferior to 30 Gy (10-year PFS, 84% v 84%; HR, 1.0; 95% CI, 0.7 to 1.5). In
contrast, PFS was inferior in ABVD-treated patients receiving 20 Gy instead of 30
Gy IF-RT (10-year PFS, 76% v 84%; HR, 1.5; 95% CI, 1.0 to 2.1). No differences in
OS or second neoplasias were observed in in both trials. Conclusion Long-term
follow-up data of the four randomized trials largely support the current risk
adapted therapeutic strategies in early-stage HL. Nevertheless, continued follow
up is necessary to assess the long-term safety of currently applied therapeutic
strategies.
PMID- 28418764
TI - Disease Surveillance of California Ground Squirrels ( Spermophilus beecheyi ) in
a Drive-through Zoo in Oregon, USA.
AB - Rodents and other small wild mammals are often considered to be pests and vectors
for disease in zoos that house small populations of valuable threatened and
endangered animals. In 2005, three nonhuman primates at a drive-through zoo in
Oregon, US, acquired tularemia from an unknown source. Due to an abundance of
California ground squirrels ( Spermophilus beecheyi ) on zoo grounds, we
instituted serosurveillance of this species from July through September 2008 to
determine the prevalence of antibodies against pathogens considered to be
potentially transmissible to collection animals. Serologic testing was performed
for Francisella tularensis ; Leptospira interrogans serovars Canicola,
Grippotyphosa, Hardjo, Icterohemorrhagiae, and Pomona; Toxoplasma gondii ; and
Yersinia pestis . All squirrels were seronegative for Yersinia pestis (0%; 0/45)
and Toxoplasma gondii (0%; 0/20); there was a prevalence of 2% (1/45) for
Francisella tularensis antibodies and 57% (24/42) were positive for various
Leptospira serovars. Although it remains unclear whether ground squirrels present
a significant risk for transmission of disease to zoo animals, vaccination of
high-risk zoo animals against leptospirosis warrants consideration. Beyond this,
continued vigilance and persistence with various forms of pest control may reduce
the likelihood of disease transmission from wildlife hosts to animals in human
care.
PMID- 28418765
TI - Brucella ceti Infection in a Common Minke Whale ( Balaenoptera acutorostrata )
with Associated Pathology.
AB - There are three major lineages of marine mammal strains of Brucella spp.:
Brucella ceti ST23, found predominantly in porpoises; B. ceti ST26, in pelagic
delphinids and ziphiids; and Brucella pinnipedialis ST24/25, predominantly in
seals. The isolation of Brucella spp. in mysticetes has been described only in
common minke whales ( Balaenoptera acutorostrata ) in Norway and Scotland. We
report a third case of Brucella infection and isolation in a minke whale
associated with a large abscess. In contrast to the two previous reports that
involved isolates of B. pinnipedialis ST24 or the porpoise-associated B. ceti
complex ST23, this case was associated with the dolphin-associated B. ceti ST26.
Thus, minke whales can be infected naturally with members of all the distinct
major lineages of Brucella associated with marine mammals. This report is unique
in that the B. ceti ST26 did not originate from a pelagic delphinid or a beaked
whale.
PMID- 28418766
TI - Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.
AB - Major depressive disorder (MDD) is not a single disease, but a number of various
ailments that form one entity. Psychomotor retardation, anhedonia, sleep
disorders, an increased suicide risk, and anxiety are the main symptoms that
often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one
of the proinflammatory cytokines, seems to be overexpressed during certain mental
disorders, including MDD. Overexpression of IL-6 in depression is thought to be a
factor associated with bad prognosis and worse disease course. IL-6 may directly
affect brain functioning and production of neurotransmitters; moreover, its
concentration is correlated with certain clinical symptoms within the wide range
of depressive symptomatology. Furthermore, there is a strong correlation between
IL-6 synthesis and psychosomatic functioning of the patient. This article
discusses potential sources and significance of IL-6 in the pathogenesis of
depression.
PMID- 28418767
TI - Randomized Controlled Trial of Survivorship Care Plans Among Low-Income,
Predominantly Latina Breast Cancer Survivors.
AB - Purpose The purpose of this study was to examine the effects of a randomized
controlled trial (RCT) of treatment summaries and survivorship care plans coupled
with a nurse counseling session, primarily on physician implementation of and
secondarily on patient adherence to recommended survivorship care, among a low
income population of breast cancer survivors (survivors). Methods We recruited
212 low-income, predominantly Latina (72.6%) survivors with stage 0 to III breast
cancer, with an average age of 53 years, from two Los Angeles County public
hospitals into an RCT of a survivorship care nurse counseling session coupled
with the provision of individualized treatment summaries and survivorship care
plans to patients and their health care providers from December 2012 to July
2014. One hundred seven survivors received the experimental intervention, and 105
survivors received usual care. Multiple linear regression analyses were performed
to assess intervention effects on physician implementation of and patient
adherence to recommended survivorship care. Scales that served as covariables
were Knowledge of Survivorship Issues, Perceived Efficacy in Patient-Physician
Interactions, and Satisfaction With Care and Information. Results Survivors in
the intervention group reported greater physician implementation of recommended
breast cancer survivorship care, for example, treatment of depression or hot
flashes, than did those in the control group (adjusted difference, 16 +/- 5.3; P
= .003). Baseline Satisfaction With Care and Information was positively
associated with physician implementation (coefficient, 5.2 +/- 2.2; P = .02).
Being married/partnered (-11.8 +/- 4.0; P = .004) and age (-0.5 +/- 0.2; P =
.028) were negatively associated with patient adherence. Conclusion To our
knowledge, this is the first RCT of survivorship care plans to show benefits in
clinical outcomes, in this case, showing increased physician implementation of
recommended breast cancer survivorship care in the intervention group, compared
with the control group.
PMID- 28418768
TI - Lipid biosynthesis: When the cell cycle meets protein synthesis?
PMID- 28418769
TI - Persistency of Neutralizing Anti-Interferon-beta Antibodies in Patients with
Multiple Sclerosis Treated with Subcutaneous Interferon-beta Depends on Antibody
Titers, IgG Subclasses, and Affinity Maturation.
AB - Neutralizing antibodies may affect interferon (IFN)-beta treatment efficacy, but
mechanisms of neutralizing anti-drug antibody (ADA) evolution are not fully
elucidated. We investigated the relationship between ADA titers, IgG subclass
profile, and binding affinity with the development and persistency of
neutralizing ADA in relapsing-remitting multiple sclerosis (MS) patients treated
with subcutaneous IFN-beta. A total of 94 patients, who had blood sampling at
months 6, 12, 24, and 36 during IFN-beta therapy, were included into this
retrospective study and stratified to the following: non-neutralizing, transient,
and persistent neutralizing ADA status. Patients without or with transient
neutralizing ADA displayed predominantly IgG1 and IgG3 subclasses, lower ADA
titers, and antibody binding affinity compared with patients having persistent
neutralizing ADA, in whom the predominant IgG subclasses were IgG2 and IgG4.
Overall, ADA binding affinity positively correlated with IgG4 and neutralizing
ADA titers, but negatively with IgG3 titers. Persistency of neutralizing ADA was
predicted by their titers at month 24 and month 36 of treatment and by an
increase of antibody affinity within the second year of IFN-beta treatment. The
humoral immune response to IFN-beta observed in MS patients as a result of IFN
beta therapy is a multifactorial process that is influenced by ADA titers,
affinity maturation, and IgG subclass switching.
PMID- 28418770
TI - Gene Silencing Activity and Hepatic Accumulation of Antisense Oligonucleotides
Bearing Cholesterol-Conjugated Thiono Triester at the Gap Region.
AB - Cholesterol (Chol) conjugation to the 5' or 3' end of antisense oligonucleotide
(ASO) enables delivery to the liver, and Chol conjugation at the gap region can
also be expected to improve delivery to the liver. In this study, we synthesized
ASOs bearing the Chol-conjugated thiono triester and evaluated their activity and
hepatic accumulation. We found that Chol conjugations at the gap region improved
in vitro activity and hepatic accumulation when compared to unconjugated ASOs.
However, Chol conjugation with phosphorothioate linkage did not improve in vivo
activity in the liver, suggesting the importance of cleaving the phosphodiester
between ASO and Chol. These results offer useful information for tuning the
oligonucleotide structure to improve pharmaceutical properties and designing ASOs
for multiple ligand conjugations and combinations with end modification.
PMID- 28418772
TI - Geographical Clusters and Predictors of Rabies in Three Southeastern States.
AB - The rabies virus causes progressive encephalomyelitis that is fatal in nearly
100% of untreated cases. In the United States, wildlife act as the primary
reservoir for rabies; prevention, surveillance, and control costs remain high.
The purpose of this study is to understand the current distribution of wildlife
rabies in three southeastern states, with particular focus on raccoons as the
primary eastern reservoir, as well as identify demographic and geographic factors
which may affect the risk of human exposure. This ecologic study obtained county
level rabies surveillance data from state health departments and the United
States Department of Agriculture Wildlife services for North Carolina, Virginia,
and West Virginia from 2010 to 2013. A spatial statistical analysis was performed
to identify county clusters with high or low rates of raccoon rabies in the three
states. Potential demographic and geographic factors associated with these
varying rates of rabies were assessed using a multivariable negative binomial
regression model. In North Carolina, raccoons constituted 50% of positive tests,
in Virginia, 49%, and in West Virginia, 50%. Compared to persons residing in West
Virginia counties, persons in North Carolina counties had 1.67 times the risk of
exposure (p < 0.0001) to a rabid raccoon and those in Virginia counties had 1.82
times the risk of exposure (p < 0.0001) to a rabid raccoon. Compared to those
counties where farmland makes up less than 17% of the total area, persons
residing in counties with 17-28% farmland had a 32% increased risk of exposure to
a rabid raccoon. In counties with 28-39% farmland, there was an 84% increased
risk of exposure. State, rurality, and percent of area designated as farmland
were the best predictors of risk of raccoon rabies exposure. Further research is
needed to better understand the effect of the oral rabies vaccine program in
controlling the risk of human exposure to raccoon rabies.
PMID- 28418773
TI - Willingness to Use Mobile Health in Glaucoma Patients.
AB - INTRODUCTION: Development of mobile health (m-health) in China carries tremendous
potential, especially for glaucoma, one of the major chronic ophthalmic diseases
afflicting millions of people. However, little research has been undertaken to
investigate the willingness of glaucoma patients to use m-health and the factors
influencing their decisions. SUBJECTS AND METHODS: This was a cross-sectional
study. A self-administered or face-to-face interview survey was performed on
1,487 patients with glaucoma at the outpatient glaucoma service, Zhongshan
Ophthalmic Center, Sun Yat-sen University. Questionnaires captured patients'
demographic data, WeChat access, and willingness to receive m-health. The data
were analyzed by single factor chi-square test. Multiple logistic regression
revealed the motivators and barriers to accept m-health adoption. RESULTS: One
thousand ninety-seven valid questionnaires were obtained. Seven hundred twenty
five respondents (66.1%) were willing to participate in m-health programs. 65.4%
were younger than 60 years old. 40.9% had travel time from home to hospital of >3
h. 63.6% had more than four follow-up visits for glaucoma. 86.5% experienced
trouble events during clinic visits. The overall WeChat usage rate was 61.7%.
Age, travel time, number of visits, trouble events in clinic, and WeChat access
in patients with glaucoma were related to the willingness to use m-health (p <
0.05). CONCLUSIONS: Most patients with glaucoma were willing to participate in m
health programs, which are essential to increasing and improving access to care.
PMID- 28418771
TI - Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory
CD8+ T Cells.
AB - Respiratory virus infections, such as those mediated by influenza virus,
parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory
syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for
substantial morbidity and mortality, especially in children and older adults.
Furthermore, the potential emergence of highly pathogenic strains of influenza
virus poses a significant public health threat. Thus, the development of vaccines
capable of eliciting long-lasting protective immunity to those pathogens is a
major public health priority. CD8+ Tissue-resident memory T (TRM) cells are a
newly defined population that resides permanently in the nonlymphoid tissues
including the lung. These cells are capable of providing local protection
immediately after infection, thereby promoting rapid host recovery. Recent
studies have offered new insights into the anatomical niches that harbor lung
CD8+ TRM cells, and also identified the requirement and limitations of TRM
maintenance. However, it remains controversial whether lung CD8+ TRM cells are
continuously replenished by new cells from the circulation or permanently lodged
in this site. A better understanding of how lung CD8+ TRM cells are generated and
maintained and the tissue-specific factors that drive local TRM formation is
required for optimal vaccine development. This review focuses on recent advance
in our understanding of CD8+ TRM cell establishment and maintenance in the lung,
and describes how those processes are uniquely regulated in this tissue.
PMID- 28418774
TI - Arsenic in the groundwater: Occurrence, toxicological activities, and remedies.
AB - Arsenic (As) contamination in groundwater has become a geo-environmental as well
as a toxicological problem across the globe affecting more than 100-million
people in nearly 21 countries with its associated disease "arsenicosis." Arsenic
poisoning may lead to fatal skin and internal cancers. In present review, an
attempt has been made to generate awareness among the readers about various
sources of occurrence of arsenic, its geochemistry and speciation, mobilization,
metabolism, genotoxicity, and toxicological exposure on humans. The article also
emphasizes the possible remedies for combating the problem. The knowledge of
these facts may help to work on some workable remedial measure.
PMID- 28418775
TI - Research 101: An Initiative to Encourage and Facilitate Quality Resident Research
in a Military Setting.
AB - Objective Describe and evaluate a structured research program initiated at a
tertiary Department of Defense (DOD) Medical Training Facility (MTF) to encourage
and facilitate the conduct of research investigations, specifically among
residents and junior or inexperienced investigators, but applicable for all DOD
otolaryngology (ENT) and audiology providers. Methods A new comprehensive program
was deployed in the ENT clinic at Madigan Army Medical Center (MAMC) to help
improve the research program. Identified gaps in research methods and regulatory
training were incorporated into the existing graduate medical education program
along with structured mentorship between residents and senior staff. Academic
achievements (eg, research protocols, publications, presentations at
national/international meetings, and funding) for the ENT clinic were examined
from 1992 to 2016, and changes in academic achievements were analyzed for
success. Results The implementation of a structured research curriculum improved
the number of protocols submitted and the quality of research being accepted for
publication (ie, journal impact factor). Funding for research increased
significantly to represent a third of the total research portfolio for the entire
hospital. Discussion The benefit of employing a research specialist to oversee
the resident research experience can greatly influence the quantity and quality
of a resident program's research portfolio. Implications for Practice Improving
resident research activity can potentially advance the quality of the resident
program, help with evidence-based medical approaches, and increase residents'
chances of matching for fellowship.
PMID- 28418776
TI - 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic
metabolites of pyrrolizidine alkaloids.
AB - Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic
phytochemicals. Metabolism of PAs in vivo generates four (+/-)-6,7-dihydro-7
hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed
to be responsible for PA-induced liver tumor formation in rats. In this present
study, we determined that the same set of DHP-DNA adducts was formed upon the
incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human
hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7
cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to
form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor
formation.
PMID- 28418777
TI - ER/LA opioid REMS and accredited education: Survey results provide insight into
clinical roles, educational needs, and learner preferences.
AB - BACKGROUND: The Collaborative for REMS (Risk Evaluation and Mitigation Strategy)
Education (CO*RE) includes 13 organizations that provide REMS Program Companies
(RPC) grant-supported accredited education on extended-release and long-acting
(ER/LA) opioid therapy. This report summarizes results of a survey designed to
investigate the impact of participant criteria and to better understand the roles
and preferences of continuing medical education/continuing education (CME/CE)
participants. METHODS: In April 2015, the authors made an online survey available
to an estimated 10,000 clinicians who had completed a CO*RE CME/CE activity since
2013. The purpose of the survey was to (1) examine possible reasons learners may
underreport prescribing status, (2) investigate ways in which learners engage in
nonprescribing roles relevant to reducing adverse patient outcomes, and (3)
determine the acceptability of a potential test-based learning tool that allows
participants with mastery to test out in lieu of participating in 2- to 3-hour
education. RESULTS: Findings revealed that there was little confusion or
reluctance by learners to answer questions about Drug Enforcement Administration
(DEA) licensing and whether they prescribed opioids in the past year. REMS
"prescriber" education covers opioid management responsibilities that are
distributed among team members who play critical nonprescribing roles in reducing
serious adverse outcomes from both ER/LA and immediate-release (IR) opioids.
Seventy-three percent of study participants would favor a test-based learning
tool should future circumstances warrant it. CONCLUSION: The authors concluded
the likelihood of underreporting is small, but there is an opportunity to clarify
license and prescribing questions; opioid management responsibilities are
distributed among nonprescribing team members who play roles in reducing adverse
outcomes from both ER/LA and IR opioids, who would therefore benefit from REMS
education; and clinicians favor a test-based learning tool, should future
circumstances warrant it. These findings could have implications for planning
future ER/LA opioid REMS curriculum and for setting and interpreting training
goals for the US Food and Drug Administration's (FDA) ER/LA opioid REMS program.
PMID- 28418778
TI - Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington
State.
AB - OBJECTIVES: Examine associations between pesticide exposure and signs or symptoms
of parkinsonism. METHODS: Prior to the 2014 pesticide spray season, the authors
examined 38 active pesticide handlers aged 35 to 65 (median: 43.5) who
participated in the State of Washington's cholinesterase monitoring program in
the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in
fruit orchards. A movement disorder specialist assessed the workers using the
Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3).
Participants also self-reported work and medical histories, including the UPDRS
activities of daily living subscore 2 (UPDRS2). The authors explored the relation
between these scores and lifetime occupational pesticide exposure while
accounting for age. RESULTS: All participants were Hispanic men born in Mexico
who had worked in agriculture for 4 to 43 years (median: 21 years, including 11
years applying pesticides, mostly in the United States). Ten participants (26%)
reported difficulty with one or more UPDRS2 activities of daily living (maximum =
2), and nine (24%) had a UPDRS3 >0 (maximum = 10). The most common symptom and
sign, respectively, were excess saliva (n = 6) and action tremor (n = 5). UPDRS2
and UPDRS3 scores were unrelated to the number of years applying pesticides, but
UPDRS3, especially action tremor, was positively associated with living on or by
a farm. CONCLUSIONS: Symptoms and signs of parkinsonism were absent to mild in
this small sample of active workers who apply cholinesterase-inhibiting
insecticides in Washington State, USA. Future studies should be larger and
examine older, retired workers with greater cumulative exposure to agricultural
pesticides at work and home, including other types of agricultural pesticides.
PMID- 28418779
TI - Determining a Successful Nasal Airway Surgery: Calculation of the Patient
Centered Minimum Important Difference.
AB - Objective Determine whether the patient-identified minimum important difference
(MID) in Nasal Obstruction Symptom Evaluation (NOSE) score differs from a
statistically calculated estimate of MID in patients with septal deviation
undergoing nasal airway surgery. Study Design Prospective cohort. Setting
Tertiary academic referral center. Subjects Patients with nasal obstruction due
to septal deviation. Methods Patients completed the NOSE questionnaire
preoperatively and indicated the change from their baseline score that they would
consider the minimum improvement required to define the septoplasty with
turbinate reduction as successful. A previously published distribution-based
approach was used to estimate the MID based on baseline NOSE scores. Scores were
reported both as a raw score and as a percentage of patients' baseline scores.
One-sample t test was used to compare the statistically estimated MID to the
patient-reported MID. Results Seventy-six patients were included. The mean (SD)
baseline NOSE score was 12.9 (4.03). The mean (SD) patient-identified MID was 5.3
(2.1), corresponding to a 41.1% change (95% confidence interval, 37.2-41.3) from
baseline. The statistically estimated MID was 5.2 points (40.3% reduction from
baseline scores). The estimated MID was not significantly different from the
patient-identified MID ( P = .4). Conclusion In patients with septal deviation,
an improvement of approximately 40% in their nasal obstructive symptoms as
assessed by the NOSE questionnaire is required to define a nasal airway surgery
as successful. The patient-identified and the statistically calculated MIDs were
similar. Furthermore, this MID can be used to guide research, improving the
ability to use the NOSE score as a dichotomous scoring measure (treatment
success/failure) and estimating sample size.
PMID- 28418780
TI - Unique phylogenetic position of the African truffle-like fungus, Octaviania
ivoryana (Boletaceae, Boletales), and the proposal of a new genus,
Afrocastellanoa.
AB - The sequestrate (truffle-like) basidiomycete Octaviania ivoryana was originally
described based on collections from Zimbabwe, Kenya, Guinea, and Senegal. This
species has basidiomes that stain blue-green and basidiospores with crowded
spines that are characteristic of the genus Octaviania. However, O. ivoryana is
the only Octaviania species described from sub-Saharan Africa, and the
phylogenetic relationship of the species to other species of Octaviania sensu
stricto has not been previously investigated. We examined the phylogenetic
position of the isotype and paratype specimens of O. ivoryana based on two nuc
rDNA loci-ITS1-5.8S-ITS2 (internal transcribed spacer [ITS]) and partial 28S-and
the translation elongation factor 1-alpha gene. The resultant phylogenies
indicate that O. ivoryana does not belong to Octaviania s. s. but instead forms a
clade with the epigeous bolete genus, Porphyrellus sensu stricto (i.e., P.
porphyrosporus and allies). The internal transcribed spacer phylogeny also
recovers a monophyletic clade that includes sequences from O. ivoryana basidiomes
as well as sequences from ectomycorrhizal root tips of Uapaca, Anthonotha, and
assorted ectomycorrhizal Fabaceae species, suggesting that there is likely
additional undescribed diversity within the lineage. We accordingly propose a new
genus, Afrocastellanoa M.E. Sm. & Orihara, to accommodate the species O.
ivoryana. Afrocastellanoa is morphologically distinct from Octaviania in the
combination of a solid gleba, multilayered peridium, and the lack of distinct
hymenium within the gleba. Our data suggest that the genus Afrocastellanoa is a
unique sequestrate lineage with one described species and several undescribed
species, all of which likely form ectomycorrhizas with African trees.
PMID- 28418781
TI - Induction Chemotherapy plus Concurrent Chemoradiotherapy vs Concurrent
Chemoradiotherapy in Elderly Patients with Advanced Nasopharyngeal Carcinoma.
AB - Objective This study aimed to compare survival and toxicity between induction
chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) and concurrent
chemoradiotherapy (CCRT) alone in elderly patients with advanced nasopharyngeal
carcinoma (NPC). Study Design Propensity-matched analysis of survival and
toxicity in a retrospective elderly cohort. Setting Department of Medical
Oncology, Jingzhou Hospital, Tongji Medical College, Huazhong University of
Science and Technology, China. Subjects and Methods In total, 193 patients with
stage III to IVb NPC who were treated with IC + CCRT or CCRT alone were enrolled.
A cohort with suitable propensity scores was created (82 patients in the IC +
CCRT group and 82 patients in the CCRT group). Survival and toxicity were
compared between the 2 groups. Results For the IC + CCRT group and the CCRT
group, the 5-year locoregional failure-free survival (LRFFS) rate was 80.4% and
77.2% ( P = .53), the 5-year distant failure-free survival (DFFS) rate was 80%
and 76.9% ( P = .517), the 5-year overall survival (OS) rate was 71.8% and 60.5%
( P = .26), and the 5-year cancer-specific survival (CSS) rate was 75.3% and
66.7% ( P = .144), respectively. There was a significant difference in the
cumulative incidence of all grade 3 to 4 toxicities between the 2 groups (29.9%
vs 17.7%, P = 4.8 * 10-6). Conclusions IC + CCRT had a high cumulative incidence
of grade 3 to 4 toxicities in elderly patients with advanced NPC, while there
were no improvements in 5-year LRFFS rate, DFFS rate, OS rate, or CSS rate
between patients who underwent the IC + CCRT vs CCRT alone. Concurrent
chemoradiotherapy alone is still the standard of treatment.
PMID- 28418782
TI - Knockdown of IL-8 Provoked Premature Senescence of Placenta-Derived Mesenchymal
Stem Cells.
AB - Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due
to their tumor tropism can serve as vehicles for delivering therapeutic agents to
tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect
of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use
in cancer gene therapy. However, little is known concerning the effect of
endogenously secreted IL-8 on MSCs. We performed studies using placenta-derived
MSCs (PMSCs) to determine whether knockdown of IL-8 would influence their
biological activity. We first verified that IL-8 and its membrane receptor CXCR2,
but not CXCR1, were highly expressed in PMSCs. We then employed lentivirus
mediated small hairpin RNA interference to generate stable IL-8-silenced PMSCs,
which displayed a variety of characteristic senescent phenotypes. We observed
that at day 9 post-transfection, IL-8-silenced PMSCs had become larger and
displayed a more flattened appearance when compared with their controls.
Moreover, their proliferation, colony forming unit-fibroblast formation,
adipogenic and osteogenic differentiation, and immunosuppressive potentials were
significantly impaired. Enhanced senescence-associated beta-galactosidase (SA
beta-gal) activity and specific global gene expression profiles confirmed that IL
8 silencing evoked the senescence process in PMSCs. Increased levels of p-Akt and
decreased levels of FOXO3a protein expression suggested that reactive oxygen
species played a role in the initiation and maintenance of senescence in IL-8
silenced PMSCs. Notably, the majority of CXCR2 ligands were downregulated in
presenescent IL-8-silenced PMSCs but upregulated in senescent cells, indicating
an antagonistic pleiotropy of the IL-8/CXCR2 signaling pathway in PMSCs. This
effect may promote the proliferation of young cells and accelerate senescence of
old cells.
PMID- 28418783
TI - Locoregional Flaps for Oral Cavity Reconstruction: A Review of Modern Options.
AB - Objective To review state-of-the-art modifications and advances in soft tissue
local and regional flap reconstruction of the oral cavity and to determine the
role these techniques play in current practice. Data Sources Review of the
literature regarding oral cavity reconstruction. Review Methods The authors
describe advances in locoregional reconstructive options and assimilate data from
the literature that compare recent advances to the historic standards.
Conclusions Modern advances in regional reconstruction of the oral cavity offer
outstanding results and demonstrate potential advance over free tissue transfer.
These modifications demonstrate the prominent role that regional reconstruction
can play in oral cavity reconstruction. Implications for Practice With a more
complete understanding of these options, the surgeon is better able to tailor the
reconstruction to the needs of the patient to provide high-quality cost-effective
care.
PMID- 28418784
TI - A Fresh Cadaver Model for the Instruction of Ultrasound-Guided Fine-Needle
Aspiration of Thyroid Nodules.
AB - Objective The aim of our study is to determine if a fresh cadaver model (FCM) for
the instruction of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid
nodules is a practical method for instruction. Study Design Pre- and
postinstruction assessment of medical students' ability to perform US-guided FNA
of artificially created thyroid nodules placed adjacent to the thyroid gland of a
fresh cadaver. Setting University-based fresh cadaver laboratory. Subjects and
Methods Study participants included a total of 17 first- and second-year medical
students with minimal US training. Technical skills were assessed using a 10-item
checklist. In addition, a cognitive assessment regarding the indications,
contraindications, and complications of the procedure was completed. A
postinstruction assessment was provided for participants 5 weeks after their
initial assessment. Differences between pre- and postinstruction assessment
scores of technical skills were analyzed using McNemar's test. The mean cognitive
knowledge gain was analyzed using a paired 2-sample t test. Results Eight of 10
items on the skills checklist were statistically significant between pre- and
postinstruction skills assessment ( P < .05). There was a statistically
significant change in cognitive knowledge gain regarding the contraindications of
the procedure ( P = .001), but not for indications or complications ( P = .104
and P = .111, respectively). Conclusion US-guided FNA continues to be an
important diagnostic procedure in the workup of thyroid nodules, making it an
essential skill to integrate into surgical skills lab. Our FCM for the
instruction of US-guided FNA is the first of its kind, and this pilot study shows
this is a viable method for instruction.
PMID- 28418785
TI - Metabolomics Analysis of the Osteogenic Differentiation of Umbilical Cord Blood
Mesenchymal Stem Cells Reveals Differential Sensitivity to Osteogenic Agents.
AB - Mesenchymal stem cells (MSCs) of fetal origin, such as umbilical cord blood MSCs
(UCB MSCs), have emerged as a promising cell source for musculoskeletal tissue
regeneration because of their higher proliferation potential, lack of donor site
morbidity, and their off-the-shelf potential. MSCs differentiated toward the
osteogenic lineage exhibit a specific metabolic phenotype characterized by
reliance to oxidative phosphorylation for energy production and reduced
glycolytic rates. Currently, limited information exists on the metabolic
transitions at different stages of the osteogenic process after osteoinduction
with different agents. Herein, the osteoinduction efficiency of BMP-2 and
dexamethasone on UCB MSCs was assessed using gas chromatography-mass spectrometry
(GC-MS) metabolomics analysis, revealing metabolic discrepancies at 7, 14, and 21
days of induction. Whereas both agents when administered individually were able
to induce collagen I, osteocalcin, and osteonectin expression, BMP-2 was less
effective than dexamethasone in promoting alkaline phosphatase expression. The
metabolomics analysis revealed that each agent induced distinct metabolic
alterations, including changes in amino acid pools, glutaminolysis, one-carbon
metabolism, glycolysis, and tricarboxylic acid cycle. Importantly, we showed that
in vitro-differentiated UCB MSCs acquire a metabolic physiology similar to
primary osteoblasts when induced with dexamethasone but not with BMP-2,
highlighting the fact that metabolomics analysis is sensitive enough to reveal
potential differences in the osteogenic efficiency and can be used as a quality
control assay for evaluating the osteogenic process.
PMID- 28418786
TI - Evaluation in Mice of the Immunogenicity of a Tetravalent Subunit Vaccine
Candidate Against Dengue Virus Using Mucosal and Parenteral Immunization Routes.
AB - Our group has developed a subunit vaccine candidate against Dengue virus (DENV)
based on two different viral regions, the domain III of the envelope protein and
the capsid protein. The chimeric proteins for each serotype (DIIIC1-4),
aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation
named Tetra DIIIC. Tetra DIIIC induces a protective immune response in mice when
it is inoculated by intraperitoneal route. However, if children are the main
targets for a DENV vaccine, then a needle-free route of administration should be
attractive and advantageous. In this study, we evaluated for the first time, in
vivo, a vaccine candidate against DENV based on recombinant proteins using the
intranasal route. After three doses of Tetra DIIIC in mice, we measured the
humoral immune response against the four DENV serotypes and the corresponding
recombinant proteins. Moreover, the functionality of these antibodies was
evaluated through a plaque reduction neutralization test. Finally, to assess the
cellular immune response induced, we measured the IFN-gamma-levels secreted by
spleen cells after in vitro stimulation with DENV. The results presented in this
study indicate that the intranasal immunization with Tetra DIIIC favors the
generation of DENV-specific cell-mediated immunity. On the other hand, the
immunization using intraperitoneal and intranasal routes, simultaneously,
generate functional antibodies (anti-DIIIC and anti-DENV) and an in vitro
response of IFN-gamma secretion.
PMID- 28418787
TI - Lulworthia atlantica: a new species supported by molecular phylogeny and
morphological analysis.
AB - This study presents morphological and molecular evidence for the establishment of
a new species of Lulworthia based on the evaluation of 11 isolates of
Lulworthiales collected in two marinas on the west coast of Portugal initially
classified as Lulworthia sp. Maximum likelihood and Bayesian methods were applied
to obtain phylogenetic trees for 18S-28S and internal transcribed spacer (ITS1
5.8S-ITS2 = internal transcribed spacer [ITS]) nuc rDNA. The isolates
consistently grouped together in a distinct and highly supported clade; all other
Lulworthiales analyzed, including the available sequences of Lulworthia spp.,
segregated separately. These results were supported by common and distinctive
morphological characters and enabled recognition and description of the new
species Lulworthia atlantica. Two Portuguese isolates were confirmed as
Lulworthia cf. purpurea, and two were confirmed as asexual morphs of Zalerion
maritima.
PMID- 28418788
TI - Factors Associated with Delayed Cooling in Cardiac Arrest Patients.
AB - Therapeutic hypothermia has been shown to improve neurologic outcome in medical
cardiac arrest patients, yet little is known about factors that delay target
temperature achievement. Our primary aim was to identify factors associated with
not achieving our institutional "door-to-cool" (DTC) performance goal (emergency
department [ED] arrival to temperature of 34 degrees C) of <=4 hours. Secondary
aims included whether achievement of DTC goal was associated with timing of bolus
neuromuscular blockade (NMB), survival, or functional outcome. This was a
retrospective cohort study of a medical cardiac arrest quality improvement (QI)
database that included patients treated from November 2007 to August 2012. The
database was queried for patient demographics, arrest characteristics, specific
cooling techniques used, whether patients underwent emergent computed tomography
imaging or cardiac catheterization, and patient outcomes. Logistic regression was
used to assess the factors associated with DTC goal performance and outcomes. We
enrolled 327 patients, median age 58, median return of spontaneous circulation
(ROSC) time of 21 minutes (interquartile range [IQR] 14-29 minutes), and
shockable initial rhythm in 61%. One hundred forty-four (44%) patients survived
to hospital discharge, 133 (41%) with good functional outcome, as defined as
cerebral performance category 1-2. Induction with cold IV fluids [OR 0.50 (CI:
0.29-0.85)] and NMB administration within 2 hours of ED arrival [OR 2.95 (CI:
1.17-7.43)] was associated with achieving DTC goal. Logistic regression showed
that achievement of DTC goal <=4 hours [OR 0.59 (0.32-1.09)] was not associated
with good functional outcome. In our single-center cohort, initiation of cold
intravenous fluids (IVF) and early NMB administration were associated with
improved DTC goal performance of 4 hours. However, patients achieving DTC goals
were not associated with improved outcomes.
PMID- 28418790
TI - Distortion-product otoacoustic emissions in workers exposed to urban stressors.
AB - The study aimed to compare the distortion-product otoacoustic emissions (DPOAEs)
with the pure-tone audiometry and to analyze the changes in participants exposed
to noise. The results show a prevalence of participants with impaired DPOAEs
higher than the prevalence of participants with impaired audiometries in the
total sample, in men, and in outdoor workers and a prevalence of impaired DPOAEs
and of impaired audiometries in men higher than in women and in outdoor workers
higher than in indoor workers. The comparison of mean values between outdoor and
indoor workers shows a significant difference only on some frequencies, in the DP
gram. The results suggest a higher effectiveness of DPOAEs compared with the pure
tone audiometry in identifying the presence of any damage in individuals exposed
to noise at an early stage.
PMID- 28418789
TI - Transitions and Motivations for Substance Misuse in Prison Inmates With ADHD and
Conduct Disorder: Validation of a New Instrument.
AB - OBJECTIVE: There is a reasonable theoretical base for understanding the possible
causes and motivations behind substance misuse and its dependency. There is a
need for a reliable and valid measure that delineates the markers of substance
use from its initiation and identifies different motivations for drug use
transitioning, maintenance, and dependency. We addressed this gap in the United
Kingdom by examining and validating the Substance Transitions in Addiction Rating
Scale (STARS). METHODS: For this review, 390 male prisoners were screened for
conduct disorder and assessed with a clinical diagnostic interview for attention
deficit/hyperactivity disorder (ADHD). They completed the four STARS subscales
regarding their substance use. Exploratory structural equation modeling was
performed to assess the STARS structure and to derive factors to assess validity
against ADHD and conduct disorder diagnostic categories. RESULTS: Each of the
subscales produced meaningful and reliable factors that supported the self
medication and behavioral disinhibition hypotheses of substance use motivation.
The findings robustly show that ADHD is significantly associated with the need
for coping as a way of managing primary and comorbid symptoms, but not conduct
disorder. The findings were strongest for the combined ADHD type. DISCUSSION:
STARS has a great potential to further the understanding of the motivation behind
substance use and its dependency in different populations.
PMID- 28418792
TI - JHL News.
PMID- 28418791
TI - Superior Semicircular Canal Dehiscence Symptoms Unmasked by Ossicular Chain
Reconstruction.
PMID- 28418793
TI - Wide Variability in Caloric Density of Expressed Human Milk Can Lead to Major
Underestimation or Overestimation of Nutrient Content.
AB - BACKGROUND: Very-low-birth-weight infants continue to face significant
difficulties with postnatal growth. Human milk is the optimal form of nutrition
for infants but may exhibit variation in nutrient content. OBJECTIVE: This study
aimed to perform macronutrient analysis on expressed human milk from mothers
whose babies are hospitalized in the neonatal intensive care unit. METHODS: Up to
five human milk samples per participant were analyzed for protein, carbohydrate,
and fat content using reference chemical analyses (Kjeldahl for protein, high
pressure liquid chromatography for carbohydrates, and Mojonnier for fat). Calorie
content was calculated. RESULTS: A total of 64 samples from 24 participants was
analyzed. Wide variability was found in calorie, protein, carbohydrate, and fat
composition. The authors found an average of 17.9 kcal/ounce, with only 34% of
samples falling within 10% of the expected caloric density. CONCLUSION: The
assumption that human milk contains 20 kcal/ounce is no longer supported based on
this study. This supports promoting an individualized nutrition strategy as a
crucial aspect to optimal nutrition.
PMID- 28418795
TI - Examining Racial Disparities in Breastfeeding From a Positive Deviance Lens: A
Commentary.
PMID- 28418796
TI - Considering Inequities in Breastfeeding.
PMID- 28418794
TI - Microbial Diversity in Milk of Women With Mastitis: Potential Role of Coagulase
Negative Staphylococci, Viridans Group Streptococci, and Corynebacteria.
AB - BACKGROUND: Lactational mastitis constitutes a significant cause of premature
weaning. However, its etiology, linked to the presence of pathogenic
microorganisms, has been scarcely reported. Research aim: The aim of this study
was to describe the microbial diversity in milk samples from women suffering from
lactational mastitis and to identify more accurately a collection of isolates
belonging to coagulase-negative staphylococci, streptococci, and coryneform
bacteria. METHODS: This is a cross-sectional descriptive one-group study. A total
of 5,009 isolates from 1,849 mastitis milk samples was identified by culture,
biochemical, and/or molecular methods at the species or genus level. A more
precise identification of a collection of 211 isolates was carried out by 16S
rRNA gene sequencing. RESULTS: Mean total bacterial count in milk samples was
4.11 log10 colony-forming units/ml, 95% confidence interval [4.08, 4.15].
Staphylococcus epidermidis was the most common species being isolated from 91.56%
of the samples, whereas Staphylococcus aureus was detected in 29.74%.
Streptococci and corynebacteria constituted the second (70.20%) and third
(16.60%) most prevalent bacterial groups, respectively, found in this study. In
contrast, Candida spp. was present in only 0.54% of the samples. Sequencing of
the 16S rRNA gene revealed a high diversity of bacterial species among identified
isolates. CONCLUSION: Many coagulase-negative staphylococci, viridans group
streptococci, and corynebacteria, usually dismissed as contaminant bacteria, may
play an important role as etiologic agents of mastitis. Proper diagnosis of
mastitis should be established after performing microbiological testing of milk
based on standardized procedures. A reliable analysis must identify the mastitis
causing pathogen(s) at the species level and its(their) concentration(s).
PMID- 28418797
TI - Reframing the Context of the Breastfeeding Narrative: A Critical Opportunity for
Health Equity Through Evidence-Based Advocacy.
PMID- 28418799
TI - Association News From the ILCA Board of Directors.
PMID- 28418798
TI - Evidence of a Preventive Effect of Breastfeeding on Obstructive Sleep Apnea in
Children and Adults.
PMID- 28418800
TI - Predictors of Breastfeeding Initiation and Maintenance in an Integrated
Healthcare Setting.
AB - BACKGROUND: The American Academy of Pediatrics recommends exclusive breastfeeding
to age 6 months. Although breastfeeding rates in the United States have been
increasing over time, further improvements are needed to meet Healthy People 2020
targets. Research aim: This study examined predictors of breastfeeding initiation
and maintenance among a population of insured pregnant women. METHODS:
Participants were 1,149 pregnant women enrolled in the Pregnancy and Influenza
Project in two Kaiser Permanente regions in 2010-2011. Data were collected
through interviews at enrollment and 1 month and 6 months postpartum and through
participants' electronic medical records. RESULTS: Nearly all (99%) women
reported initiating breastfeeding. Rates of exclusive breastfeeding were 70% and
54% at 1 month and 6 months, respectively; an additional 22% and 23% of women
reported supplementing breastfeeding with formula. Of the women who supplemented,
the mean ( SD) infant age at formula introduction was 53 (62) days. Of those who
had stopped breastfeeding, the mean ( SD) infant age at cessation was 85 (59)
days. Higher maternal education level, better maternal self-rated health,
prenatal folic acid use, absence of chronic medical conditions, and infant full
term birth were significantly associated with breastfeeding maintenance.
CONCLUSION: Although rates of breastfeeding in this population were higher than
national rates, a significant number of women stopped breastfeeding or introduced
formula earlier than recommended. Two to 3 months postpartum may be a critical
period warranting additional encouragement or intervention by healthcare
providers. Mothers' education attainment, maternal health factors, and
gestational age at delivery may predict likelihood of breastfeeding maintenance.
PMID- 28418801
TI - About Research: Qualitative Methodologies.
PMID- 28418802
TI - Transfer of Low Dose Aspirin Into Human Milk.
AB - BACKGROUND: Aspirin has antipyretic and anti-inflammatory properties and is
frequently used by pregnant and lactating women. However, its transfer in human
milk when administered at low dose has not been reported. Research aim: This
study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite,
salicylic acid, into human milk following the use of low dose aspirin. METHODS:
In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours
from seven breastfeeding women after a steady-state daily dose of 81 mg of
aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined
by liquid chromatography-tandem mass spectrometry. RESULTS: Acetylsalicylic acid
levels were below the limit of quantification (0.61 ng/ml) in all the milk
samples, whereas salicylic acid was detected at very low concentrations. The
average concentration of salicylic acid observed was 24 ng/ml and the estimated
relative infant dose was 0.4%. CONCLUSION: Acetylsalicylic acid transfer into
milk is so low that it is undetectable even by highly sophisticated methodology.
Salicylic acid does appear in the human milk in comparatively low amounts, which
are probably subclinical in infants. Thus, the daily use of an 81-mg dose of
aspirin should be considered safe during lactation.
PMID- 28418803
TI - An Ecological Momentary Assessment of Primiparous Women's Breastfeeding Behavior
and Problems From Birth to 8 Weeks.
AB - BACKGROUND: Primiparous women are at risk for early, unintended breastfeeding
reduction and cessation. Breastfeeding patterns that contribute to these outcomes
require further exploration. Research aim: This study aimed to describe early,
"real-time" breastfeeding behaviors and perceived problems of primiparous women.
METHODS: First-time mothers intending to exclusively breastfeed downloaded a
commercial infant-feeding app during their postpartum hospitalization. Women
logged feedings and their breastfeeding experiences, as they occurred, through 8
weeks postpartum. Additional feeding and background data were collected via
electronic medical records and questionnaires administered at enrollment and 2
and 8 weeks postpartum. Summary statistics were compiled to examine weekly
breastfeeding behaviors and problems. RESULTS: In this sample of 61 primarily
highly educated, White women committed to breastfeeding, 38% ( n = 23) used
formula during the postpartum hospitalization and 68% ( n = 34) used formula at
least once by 2 weeks. Nine women stopped breastfeeding during the study. Women
using any formula in the hospital and those with less positive baseline attitudes
toward breastfeeding were less likely to be exclusively breastfeeding at 2 and 8
weeks, respectively ( p < .05). There was a trend toward declining at-breast
feeds and high rates of milk expression during the study. Breastfeeding problems
peaked at Week 2, with 81% of women ( n = 39) endorsing at least one problem at
that time. The most prevalent problems included perception of inadequate milk,
pain, latching, and inefficient feeds. CONCLUSION: Interventions to address
suboptimal breastfeeding in primiparous women should consider the pervasiveness
of early milk expression and in-hospital formula supplementation in this
population, as well as the trajectory of common problems.
PMID- 28418804
TI - Determinants of Nonmedically Indicated In-Hospital Supplementation of Infants
Whose Birthing Parents Intended to Exclusively Breastfeed.
AB - BACKGROUND: Despite high rates of intention to exclusively breastfeed, rates of
exclusive breastfeeding in Canada are low. Supplementation may begin in hospital
and is associated with reduced breastfeeding duration. Research aim: The aim of
this investigation was to explore determinants of in-hospital nonmedically
indicated supplementation of infants whose birthing parents intended to
exclusively breastfeed. METHODS: This study is a cross-sectional one-group
nonexperimental design, focused on participants who intended to exclusively
breastfeed for 6 months ( n = 496). Data were collected between October 2011 and
October 2015 in Newfoundland and Labrador. Variables measured included age;
rural/urban location; education; income; race; marital status; parity; smoking
status; having been breastfed as an infant; previous breastfeeding experience;
Iowa Infant Feeding Attitude Scale score; delivery mode; infant birth weight;
birth satisfaction; skin-to-skin contact; length of participant's hospital stay;
breastfeeding advice from a lactation consultant, registered nurse, or physician;
and first impression of breastfeeding. We evaluated determinants of in-hospital
nonmedically indicated supplementation using bivariate and multivariate logistic
regression analyses. RESULTS: Overall, 16.9% ( n = 84) of infants received
nonmedically indicated supplementation in hospital. Multivariate modeling
revealed four determinants: low total prenatal Iowa Infant Feeding Attitude Scale
score (odds ratio [OR] = 1.96, 95% confidence interval [CI] [1.18, 3.27]), no
previous breastfeeding experience (OR = 2.03, 95% CI [1.15, 3.61]), negative
first impression of breastfeeding (OR = 2.67, 95% CI [1.61, 4.43]), and receiving
breastfeeding advice from a hospital physician (OR = 2.86, 95% CI [1.59, 5.15]).
CONCLUSION: Elements of the hospital experience, self-efficacy, and attitudes
toward infant feeding are determinants of nonmedically indicated supplementation
of infants whose birthing parents intended to exclusively breastfeed.
PMID- 28418805
TI - Public Attitudes Toward Breastfeeding in Public Places in Ottawa, Canada.
AB - BACKGROUND: In Ontario, Canada, breastfeeding in public is a protected right, yet
even with these laws, attitudes toward breastfeeding in public can serve as a
barrier to breastfeeding. Research aim: This study assesses public support for
breastfeeding in public among adults in Ottawa, Ontario, and examines
sociodemographic associations with negative attitudes toward public
breastfeeding. METHODS: Data from the 2015 Rapid Risk Factor Surveillance System
(RRFSS), a population health telephone survey, were obtained for Ottawa. Adults
ages 18 years and older were asked whether it was acceptable for a mother to
breastfeed her baby in a restaurant and shopping mall ( n = 1,276). Descriptive
statistics and regression were used to describe sociodemographic characteristics
associated with negative attitudes. RESULTS: Overall, 75% of respondents agreed
that it was acceptable for a mother to breastfeed her baby in both a restaurant
and shopping mall (restaurant: 78%; shopping mall: 81%). Respondents who did not
have children at home, were less educated, had a mother tongue language other
than French or English and who were retirees were less likely to support
breastfeeding in restaurants and shopping malls. In addition, women and
immigrants living in Canada for more than 15 years were less likely to support
breastfeeding in shopping malls. CONCLUSION: Despite a law to support public
breastfeeding in Ontario, there is room to improve attitudes toward public
breastfeeding. Increased public support for public breastfeeding can support
women and children to achieve their feeding goals, particularly for those wanting
to exclusively breastfeed.
PMID- 28418806
TI - Lactation Newsmakers: An Interview With Laurence Grummer-Strawn, MPA, MA, PhD.
PMID- 28418807
TI - Coagulase-Negative Staphylococci in Human Milk From Mothers of Preterm Compared
With Term Neonates.
AB - BACKGROUND: Human milk is the preferred nutrition for neonates and a source of
bacteria. Research aim: The authors aimed to characterize the molecular
epidemiology and genetic content of staphylococci in the human milk of mothers of
preterm and term neonates. METHODS: Staphylococci were isolated once per week in
the 1st month postpartum from the human milk of mothers of 20 healthy term and 49
preterm neonates hospitalized in the neonatal intensive care unit. Multilocus
variable-number tandem-repeats analysis and multilocus sequence typing were used.
The presence of the mecA gene, icaA gene of the ica-operon, IS 256, and ACME
genetic elements was determined by PCR. RESULTS: The human milk of mothers of
preterm compared with term neonates had higher counts of staphylococci but lower
species diversity. The human milk of mothers of preterm compared with term
neonates more often contained Staphylococcus epidermidis mecA (32.7% vs. 2.6%),
icaA (18.8% vs. 6%), IS 256 (7.9% vs. 0.9%), and ACME (15.4% vs. 5.1%), as well
as Staphylococcus haemolyticus mecA (90.5% vs. 10%) and IS 256 (61.9% vs. 10%).
The overall distribution of multilocus variable-number tandem-repeats analysis
(MLVA) types and sequence types was similar between the human milk of mothers of
preterm and term neonates, but a few mecA-IS 256-positive MLVA types colonized
only mothers of preterm neonates. Maternal hospitalization within 1 month
postpartum and the use of an arterial catheter or antibacterial treatment in the
neonate increased the odds of harboring mecA-positive staphylococci in human
milk. CONCLUSION: Limiting exposure of mothers of preterm neonates to the
hospital could prevent human milk colonization with more pathogenic
staphylococci.
PMID- 28418808
TI - Effects of Maternal Supplementation With Omega-3 Precursors on Human Milk
Composition.
AB - BACKGROUND: Long-chain polyunsaturated fatty acids (LC-PUFAs) are important for
newborn neurosensory development. Supplementation of breastfeeding mothers' diets
with omega-3 PUFAs, such as alpha-linolenic acid (ALA), may increase their
concentration in human milk. Research aim: This study aimed to assess human milk
composition after 15-day supplementation regimens containing either omega-3 PUFAs
or olive oil, which does not provide ALA. METHODS: A multicenter factorial
randomized trial was conducted with four groups of breastfeeding women, with each
group containing 19 to 22 women. After a 15-day ALA washout period, three groups
received supplementation with omega-3 precursors for 15 days: an enriched
margarine (M), a rapeseed oil (R), and a margarine and rapeseed oil (MR). The
fourth was unexposed to omega-3 precursors (olive oil control diet, O). After 15
days, blind determination of human milk fatty acid (FA) composition was assessed
by gas chromatography, and the FA composition was compared among groups using
variance analyses. RESULTS: Alpha-linolenic acid content, expressed as the mean
(standard deviation) total human milk FA percentage, was significantly higher
after diet supplementation with omega-3 PUFAs, with values of 2.2% (0.7%) (MR),
1.3% (0.5%) (R), 1.1% (0.4%) (M), and 0.8% (0.3%) (O at D30) ( p < .003 for each
comparison). The lowest LA-ALA ratio (5.5) was found in the MR group ( p < .001).
Docosahexaenoic acid and trans FA concentrations did not differ among groups.
CONCLUSION: In lactating women, omega-3 supplementation via the combination of
enriched margarine and rapeseed oil increased the ALA content of human milk and
generated the most favorable LA-ALA ratio for LC-PUFA synthesis.
PMID- 28418809
TI - Validation Study of Maternal Recall on Breastfeeding Duration 6 Years After
Childbirth.
AB - BACKGROUND: Breastfeeding duration is an important indicator commonly measured in
maternal and child health and nutrition research. Maternal short-term recall for
both initiation and duration of breastfeeding has been shown to be valid;
however, validity of long-term recall is not well understood. Research aim: This
study aims to assess the validity of maternal recall of breastfeeding duration 6
years after childbirth and its association with sociodemographic factors.
METHODS: Among 635 mother-child pairs, breastfeeding duration data collected
monthly throughout the 1st year after childbirth in the Infant Feeding Practices
Study II (IFPS II) were compared to recall data obtained 6 years later during the
Year 6 Follow-Up. The intraclass correlation coefficient (ICC) and Bland-Altman
plots were examined to study the agreement between the two data sets.
Sociodemographic factors associated with accurate recall to within 1 month of the
IFPS II breastfeeding duration were assessed using multivariable logistic
regression modeling. RESULTS: Maternal recall of breastfeeding duration was found
to be valid 6 years after childbirth with a small median overall bias (1 week)
toward overestimation. The overall concordance was high (ICC = 0.84), except for
high school graduates (ICC = 0.63) and smokers (ICC = 0.61). Smokers (adjusted
odds ratio = 0.52; 95% confidence interval [0.4, 0.8]) and multiparous women
(adjusted odds ratio = 0.57; 95% confidence interval [0.4, 0.9]) were also less
likely to give an accurate recall of their breastfeeding duration to within 1
month. CONCLUSION: Our study found that maternal recall of breastfeeding duration
varies by sociodemographic factors but is accurate 6 years after childbirth.
PMID- 28418810
TI - Relationship of Trochlear Morphology and Patellofemoral Joint Alignment to
Superolateral Hoffa Fat Pad Edema on MR Images in Individuals with or at Risk for
Osteoarthritis of the Knee: The MOST Study.
AB - Purpose To determine the relationship of patellofemoral joint alignment and
trochlear morphology to superolateral Hoffa fat pad (SHFP) edema on magnetic
resonance (MR) images in older adults with or at risk for osteoarthritis of the
knee. Materials and Methods Institutional review board approval and written
informed consent were obtained from all subjects. The Multicenter Osteoarthritis
Study is a prospective cohort study of older adults with or at risk for
osteoarthritis of the knee. Subjects were recruited from Birmingham, Alabama, and
Iowa City, Iowa. In this cross-sectional study, patellofemoral joint alignment
(bisect offset, patellar tilt angle, and Insall-Salvati ratio), trochlear
morphology (sulcus angle, lateral and medial trochlear inclination, and trochlear
angle) and SHFP edema were assessed on MR images of the knee. Measures of
alignment and morphology were divided into quartiles, and SHFP was determined to
be present or absent. Separate logistic regression models were used to determine
the relationship of each measure of alignment and morphology to the presence of
SHFP edema, with adjustments for age, sex, and body mass index. Results SHFP
edema was present in 152 (13.4%) of the 1134 knees that were included. When
compared with knees with measurements in the lowest quartile, knees with
measurements in the highest quartile for trochlear angle, bisect offset, and
Insall-Salvati ratios were 1.6 (95% confidence interval [CI]: 1.0, 2.6), 2.3 (95%
CI: 1.3, 4.0), and 8.9 (95% CI: 4.7, 16.9) times more likely to show SHFP edema,
respectively. No relationship was found between other measures and SHFP edema.
Conclusion A more anterior trochlear facet, a more laterally displaced patella,
and knees with patella alta were significantly associated with SHFP edema on MR
images in subjects with or at risk for osteoarthritis of the knee. (c) RSNA,
2017.
PMID- 28418812
TI - Phellinopsis lonicericola and P. tibetica spp. nov. (Hymenochaetales,
Basidiomycota), from Tibet, with a key to worldwide species.
AB - Phellinopsis (Hymenochaetaceae) was recently segregated from Phellinus.
Phellinopsis differs from other genera segregated from Phellinus in a combination
of hymenial setae, if present, mostly originating from tramal hyphae and hyaline
basidiospores becoming pale yellowish with age. In this study, two new species of
Phellinopsis, P. lonicericola and P. tibetica, from Tibet in southwestern China
were described and illustrated. Morphological data and sequences of the nuc rDNA
ITS1-5.8S-ITS2 region (internal transcribed spacer [ITS] barcode) support the
recognition of these taxa as distinct. They are morphologically compared with
other species of Phellinopsis. Notably, P. lonicericola was often found on
Lonicera together with Sanghuangporus alpinus, which was originally described
from the same locality. In addition, Phellinopsis helwingiae, known from a single
collection from Sichuan Province in midwestern China, is reported from Tibet.
Eight accepted species of Phellinopsis worldwide, each forming a terminal
lineage, grouped together as a strongly supported clade distinct from the clade
representing Phellinus. A key to the eight species of Phellinopsis is provided.
PMID- 28418811
TI - Hypertrabeculated Left Ventricular Myocardium in Relationship to Myocardial
Function and Fibrosis: The Multi-Ethnic Study of Atherosclerosis.
AB - Purpose To determine if excess greater left ventricle (LV) trabeculation is
associated with decreased average regional myocardial function, diffuse fibrosis,
or both. Materials and Methods This was a HIPAA-compliant institutional board
approved multicenter study, and all participants provided written informed
consent. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA)
underwent a comprehensive cardiac magnetic resonance (MR) examination. LV
trabeculation was measured with the maximal apical fractal dimension (FD), which
is a marker of endocardial complexity. Demographic covariates, cardiovascular
risk factors, and cardiac MR measurements were compared across quartiles of FD.
Associations between FD and peak regional systolic circumferential strain (Ecc)
and T1 time, a surrogate for diffuse myocardial fibrosis, were assessed with
multivariable linear regression models. Results A total of 1123 subjects (593
[52.8%] female; mean age, 67.1 years +/- 8.7 [standard deviation]) underwent FD
and Ecc measurement, and 992 (521 [52.5%] female; mean age, 67.1 years +/- 8.7)
underwent FD and T1 measurement. Mean FD was 1.2 +/- 0.07 in both groups, and
mean Ecc was -18.3 +/- 2.27 in the subjects who underwent FD and Ecc measurement.
Global volumes and ejection fraction showed no differences between FD quartiles.
However, with increasing FD quartile, Ecc was greater (indicating worse average
regional function) (P < .001). After adjustment, greater trabeculation was
associated with 21% worse myocardial strain (relative to the mean) per unit
change in FD (regression coefficient = 4.0%; P < .001). There was no association
between the degree of trabeculation and diffuse fibrosis measured with T1
mapping. Conclusion Average regional LV function was worse in individuals with
greater LV trabeculation, supporting the concept of hypertrabeculation being an
epiphenomenon of disease. (c) RSNA, 2017.
PMID- 28418813
TI - Radiation-Induced Deletions in Mouse Spermatogonia are Usually Large (over 200
kb) and Contain Little Sequence Similarity at the Junctions.
AB - Ionizing radiation can induce mutations, and the majority of radiation-induced
mutations in mammalian cells are deletions. The most critical types of radiation
induced DNA damage are DNA double-strand breaks, and these breaks are repaired by
either the homologous recombination (HR) pathway or the non-homologous end
joining (NHEJ) pathway. The HR pathway is not as mutagenic as the NHEJ pathway,
and it is expected that radiation-induced deletions would usually have little
sequence similarity around the deletion junction points. Here we report sequence
data from the regions around the rejoined junctions of 33 de novo copy-number
mutations (27 deletions and 6 duplications) obtained from offspring sired by male
mice that were irradiated at the spermatogonia stage and from nonirradiated
controls. The results indicate that deletions can be classified into three major
groups. In group 1, nine deletions were found to share long blocks of similar
sequences (200-6,000 bp) at the junctions and the deletion size varied
extensively (1 kb to 2 Mb) (e.g., illegitimate recombination). In group 2, five
deletions shared short identical sequences (0-7 bp) at the junctions, and the
deletion sizes were shorter than 200 kb (e.g., micro-homology-mediated repair).
Additional three-deletion candidates of this group were also found but turned out
to be inherited from mosaic parents. They are therefore not included in germline
mutations. In group 3, twelve deletions shared little sequence similarity (only 0
2 bp) at the junctions (likely due to NHEJ repair) and deletion sizes were longer
than 200 kb. Group 1 consisted of deletions found in both spontaneous and
irradiated genomes and thus, were probably caused by spontaneous events during
meiosis or DNA replication. Group 2 consisted mainly of deletions found in
nonexposed genomes. Group 3 consisted primarily of deletions that occurred in the
irradiated genomes. Among the duplications, we found no indication of any
association with radiation exposures. These results indicate that large size
(>200 kb) and little sequence similarity around the rejoined sites are likely to
be a hallmark of radiation-induced deletions in mice.
PMID- 28418814
TI - Ionizing Radiation Exposure During Pregnancy: Effects on Postnatal Development
and Life.
AB - Reliable human data on the effects of prenatal exposure to ionizing radiation are
largely based on high-dose exposures. Exposure to low doses may produce effects
that are not easily observable at birth, and may persist over the course of the
offspring's postnatal life. This is important when considering fetal programing,
a phenomenon characterized by changes in offspring phenotype due to a stress
experienced in utero. In this review, we briefly summarize the known effects of
both high- and low-dose exposure to ionizing radiation during pregnancy in
humans. There is a major consensus that the atomic bomb survivors' data shows
increased incidence of microcephaly and reductions in IQ of A-bomb survivors,
whereas, with diagnostic radiography in utero there is no conclusive evidence of
increased cancer risk. Due to the relatively limited data (particularly for low
dose exposures) in humans, animal models have emerged as an important tool to
study prenatal effects of radiation. These animal models enable researchers to
manipulate various experimental parameters and make it possible to analyze a
wider variety of end points. In this review, we discuss the major findings from
studies using mouse and rat models to examine prenatal ionizing radiation effects
in postnatal development of the offspring. In addition, we broadly categorize
trends across studies within three major stages of development: pre-implantation,
organogenesis and fetal development. Overall, long-term effects of prenatal
radiation exposure (including the possible role on the developmental programing
of disease) are important factors to consider when assessing radiation risk,
since these effects are of relevance even in the low-dose range.
PMID- 28418815
TI - Educational Activity for the Radiation Emergency System in the Northern Part of
Japan: Meeting Report on "The 3rd Educational Symposium on Radiation and Health
(ESRAH) by Young Scientists in 2016".
AB - In the northern part of Japan, close cooperation is essential in preparing for
any possible emergency response to radiation accidents because several
facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX
Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho
Village (Aomori Prefecture). After the accident at Fukushima Daiichi Nuclear
Power Plant in 2011, special attention should be given to the relationship
between radiation and human health, as well as establishing a system for managing
with a radiation emergency. In the area of Hokkaido and Aomori prefectures in
Japan, since 2008 an exchange meeting between Hokkaido University and Hirosaki
University has been held every year to have opportunities to discuss radiation
effects on human health and to collect the latest news on monitoring
environmental radiation. This meeting was elevated to an international meeting in
2014 titled "Educational Symposium on Radiation and Health (ESRAH) by Young
Scientists". The 3rd ESRAH meeting took place in 2016, with the theme
"Investigating Radiation Impact on the Environmental and Health". Here we report
the meeting findings on the continuing educational efforts after the Fukushima
incident, what was accomplished in terms of building a community educational
approaches, and future goals.
PMID- 28418816
TI - Safe and competent opioid prescribing education: Increasing dissemination with a
train-the-trainer program.
AB - BACKGROUND: Due to the high prevalence of prescription opioid misuse, the US Food
and Drug Administration (FDA) mandated a Risk Evaluation and Mitigation Strategy
(REMS) requiring manufacturers of extended-release/long-acting (ER/LA) opioids to
fund continuing education based on an FDA curricular Blueprint. This paper
describes the Safe and Competent Opioid Prescribing Education (SCOPE of Pain)
train-the-trainer program and its impact on (1) disseminating the SCOPE of Pain
curriculum and (2) knowledge, confidence, attitudes, and performance of the
participants of trainer-led compared with expert-led meetings. METHODS: SCOPE of
Pain is a 3-hour ER/LA opioid REMS education. In addition to expert-led live
statewide meetings, a 2-hour train-the-trainer (TTT) workshop was developed to
increase dissemination nationally. The trainers were expected to conduct SCOPE of
Pain meetings at their institutions. Participants of both the trainer-led and
expert-led SCOPE of Pain programs were surveyed immediately post and 2 months
post meetings to assess improvements in knowledge, confidence, attitudes, and
self-reported safe opioid prescribing practices. RESULTS: During 9 months (May
2013 to February 2014), 89 trainers were trained during 9 TTT workshops in 9
states. Over 24 months (May 2013 to April 2015), 33% of the trainers conducted at
least 1 SCOPE of Pain training, with a total of 79 meetings that educated 1419
participants. The average number of meetings of those who conducted at least 1
meeting was 2.8 (range: 1-19). The participants of the trainer-led programs were
significantly more likely to be practicing in rural settings than those who
participated in the expert-led meetings (39% vs. 26%, P < .001). At 2 months post
training, there were no significant differences in improvements in participant
knowledge, confidence, attitudes, and performance between expert-led and trainer
led meetings. CONCLUSIONS: The SCOPE of Pain TTT program holds promise as an
effective dissemination strategy to increase guideline-based safe opioid
prescribing knowledge, confidence, attitudes, and self-reported practices.
PMID- 28418817
TI - Virtual Mapping of the Frontal Recess: Guiding Safe and Efficient Frontal Sinus
Surgery.
AB - : Objective To define relationships between the frontal sinus opening, ostia of
other frontal recess cells, and endoscopic landmarks and to develop a clinically
useful framework to guide frontal sinus surgery. Study Design Retrospective
review. Setting Tertiary care academic referral center. Methods Adult patients
with computed tomography (CT) without sinonasal pathology were included. Virtual
endoscopy (using OsiriX) and corresponding CT reconstructions were used to
identify all visible ostia in the frontal recess and characterize their positions
in spaces between the uncinate/agger nasi (U), bulla ethmoidalis (EB), and middle
turbinate (MT). Results Two hundred sides in 100 patients (median age 51 years,
62% female) were analyzed. The "center" of each map was defined as the
intersection of spaces between U, EB, and MT. The frontal sinus opening was in
the "center" in 53% of frontal recesses, lateral to this position in 29%, and
anterior in 11%. When the frontal sinus opening was at the "center," anterior
ostia drained frontal Kuhn T cells in 51% and intersinus septal cells in 23%. The
skull base attachment of the apical strut of the uncinate process demarcated
medial and lateral within the space between U and EB, with the opening to the
frontal sinus medial in 68% and lateral in 31%. Left-right asymmetry in frontal
sinus openings was noted in 46% of patients. Conclusion Combining preoperative
imaging and knowledge of these anatomic relationships may facilitate more
efficient frontal outflow tract identification and instrumentation. This
represents the first and largest description of ostial configurations relative to
endoscopic structural landmarks. LEVEL OF EVIDENCE: 4.
PMID- 28418818
TI - "It is not the diet; it is the mental part we need help with." A multilevel
analysis of psychological, emotional, and social well-being in obesity.
AB - In this research, we explored the psychological, emotional, and social
experiences of individuals living with obesity, and perceptions of health care
providers. We conducted a theoretical thematic analysis using two theoretical
frameworks applied to transcripts from a previous qualitative study. Themes from
a mental well-being framework were subsequently categorized under five
environmental levels of the Social-Ecological Model (SEM). Key mental well-being
themes appeared across all levels of the SEM, except the policy level. For the
individual environment, one main theme was food as a coping mechanism and source
of emotional distress. In the interpersonal environment, two themes were (a)
blame and shame by family members and friends because of their weight and (b)
condemnation and lack of support from health professionals. In the organizational
environment, one main theme was inadequate support for mental well-being issues
in obesity management programmes. In the community environment, one major theme
the negative mental well-being impact of the social stigma of obesity. An
overarching theme of weight stigma and bias further shaped the predominant themes
in each level of the SEM. Addressing weight stigma and bias, and promoting
positive mental well-being are two important areas of focus for supportive
management of individuals living with obesity.
PMID- 28418819
TI - Cancer Genomics and Important Oncologic Mutations: A Contemporary Guide for Body
Imagers.
AB - The field of cancer genomics is rapidly evolving and has led to the development
of new therapies. Knowledge of commonly involved cellular pathways and genetic
mutations is now essential for radiologists reading oncology cases. Radiogenomics
is an emerging area of research that seeks to correlate imaging features with
cancer genotypes. Such knowledge may extend the utility of multiparametric
imaging to yield information regarding cancer prognosis and likelihood of
therapeutic response. To date, only a handful of radiogenomics studies have been
performed to evaluate solid tumors of the body, and there is much to explore.
Before doing so, however, it behooves us to have adequate background knowledge of
clinical cancer genomics to design meaningful radiogenomics projects and explore
imaging phenotypes. Herein, an up-to-date, detailed overview is provided of well
known and common mutations of solid body tumors (such as human epithelial growth
factor receptor 2, breast cancer susceptibility protein), newer genomic
alterations with potential for clinical relevance, and a discussion of known
related imaging findings, including existing radiogenomics data and other
radiologic patterns of disease. (c) RSNA, 2017 Online supplemental material is
available for this article.
PMID- 28418820
TI - Case 241: Hemiparkinsonism- Hemiatrophy-SPECT with 99mTc TRODAT-1 and Muscle MR
Imaging Abnormalities.
AB - History A 43-year-old right-handed man presented with a history of progressive
mild left-sided weakness and slowness of movements. Symptoms began 4 years
earlier, and the patient noticed a progressive decline in his daily routine due
to gait difficulties in the past year. There was no history of head trauma,
surgery, drug therapy, smoking, or alcohol abuse, nor was there any relevant
family history. Examination revealed normal cognition (29 of 30 points on the
Mini-Mental State Examination and 27 of 30 points on the Montreal Cognitive
Assessment) and normal cerebellar, sensory, cranial nerve, and autonomic
function. There was mild left-sided weakness involving the upper and lower limbs
(medical research council graded muscle strength as 4+ out of 5) that was
associated with facial hypomimia and a rigid akinetic syndrome only in the
patient's left hemibody (Unified Parkinson's Disease Rating Scale [UPDRS] part
III [motor examination], 23 out of 52 points). Mild atrophy in the left upper and
lower limbs without pain, swelling, or skin lesions was noted at physical
examination. Routine blood chemistry was normal, as were serum creatine kinase
and aldolase levels and thyroid, hepatic, and renal function. T1- and T2
weighted, fluid-attenuated inversion recovery, diffusion- and perfusion-weighted,
and contrast material-enhanced brain magnetic resonance (MR) imaging results were
normal, without basal ganglia hyperintensity, lacunae, calcification, or heavy
metal deposits. Muscle MR imaging and single photon emission computed tomography
(SPECT) with technetium 99m (99mTc) tropane dopamine transporter (TRODAT)-1 were
performed for further evaluation. This patient received levodopa and benserazide
(200 and 50 mg, respectively) four times a day and amantadine (100 mg) three
times a day without adequate improvement (UPDRS score decreased from 23 to 20
points).
PMID- 28418821
TI - In Memoriam.
PMID- 28418824
TI - Financial Forecasting and Stochastic Modeling: Predicting the Impact of Business
Decisions.
AB - In health care organizations, effective investment of precious resources is
critical to assure that the organization delivers high-quality and sustainable
patient care within a supportive environment for patients, their families, and
the health care providers. This holds true for organizations independent of size,
from small practices to large health systems. For radiologists whose role is to
oversee the delivery of imaging services and the interpretation, communication,
and curation of imaging-informed information, business decisions influence where
and how they practice, the tools available for image acquisition and
interpretation, and ultimately their professional satisfaction. With so much at
stake, physicians must understand and embrace the methods necessary to develop
and interpret robust financial analyses so they effectively participate in and
better understand decision making. This review discusses the financial drivers
upon which health care organizations base investment decisions and the central
role that stochastic financial modeling should play in support of strategically
aligned capital investments. Given a health care industry that has been slow to
embrace advanced financial analytics, a fundamental message of this review is
that the skills and analytical tools are readily attainable and well worth the
effort to implement in the interest of informed decision making. (c) RSNA, 2017
Online supplemental material is available for this article.
PMID- 28418825
TI - Science to Practice: Quantitative US Elastography Can Be Used to Quantify
Mechanical and Histologic Tendon Healing in a Rabbit Model of Achilles Tendon
Transection.
AB - Compression-based ultrasonographic (US) elastography is associated with time
dependent mechanical and histologic changes of the healing tendon in a transected
rabbit model of the Achilles tendon. This finding will lead to continued
development of quantitative US, which can be used to objectively assess a
diseased or healing tendon. With advances in the method used, clinical
translation of tendon elastography may enable clinicians to diagnose tendon
damage and track healing, which should improve both treatment and outcome.
PMID- 28418827
TI - Case 245.
PMID- 28418828
TI - A comparison of blood and cerebrospinal fluid cytokines (IL-1beta, IL-6, IL-18,
TNF-alpha) in neonates with perinatal hypoxia.
AB - Perinatal hypoxia-ischemia is a specific and important pathological event in
neonatal care practice. The data on relationship between the concentrations of
cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are
scarce. The aim of this study is to evaluate changes in interleukin (IL-1beta, IL
6, and IL-18) and tumor necrosis factor alpha (TNF-alpha) levels in newborns with
perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40
weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme
linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non
hypoxic infants of the same age sampled for clinically suspected perinatal
meningitis, but proven negative and healthy otherwise. The cytokine values in CSF
and serum samples were determined in relation to initial hypoxic-ischemic
encephalopathy (HIE) staged according the Sarnat/Sarnat method, and compared with
neurological outcome at 12 months of age estimated using Amiel-Tison procedure.
The concentrations of IL-6 and TNF-alpha in serum of PNH patients were
significantly higher compared to control group (p = 0.0407 and p = 0.023,
respectively). No significant difference between average values of cytokines in
relation to the stage of HIE was observed. Significantly higher levels of IL-6
and IL-18 corresponded to a mildly abnormal neurological outcome, while higher
levels of IL-6 and TNF-alpha corresponded to a severely abnormal neurological
outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-alpha better
corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of
birth. Also, higher serum levels of IL-6, TNF-alpha, and IL-18 corresponded
better with abnormal neurological outcome at 12 months of age, compared to CSF
values.
PMID- 28418829
TI - CTX-M-27-Producing Escherichia coli of Sequence Type 131 and Clade C1-M27,
France.
PMID- 28418832
TI - The Glossary of Prosthodontic Terms: Ninth Edition.
PMID- 28418830
TI - Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B.
mallei-like Variation in the bimA Motility Gene, Australia.
AB - Neurologic melioidosis is a serious, potentially fatal form of Burkholderia
pseudomallei infection. Recently, we reported that a subset of clinical isolates
of B. pseudomallei from Australia have heightened virulence and potential for
dissemination to the central nervous system. In this study, we demonstrate that
this subset has a B. mallei-like sequence variation of the actin-based motility
gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles,
isolates that contain the B. mallei-like variation demonstrate increased
persistence in phagocytic cells and increased virulence with rapid systemic
dissemination and replication within multiple tissues, including the brain and
spinal cord, in an experimental model. These findings highlight the implications
of bimA variation on disease progression of B. pseudomallei infection and have
considerable clinical and public health implications with respect to the degree
of neurotropic threat posed to human health.
PMID- 28418831
TI - The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of
Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological
Pretreatment of Soman-Poisoned Mice.
AB - AIM: The ability of four newly prepared reversible inhibitors of
acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and
currently used carbamate pyridostigmine to increase the resistance of mice
against soman and the efficacy of antidotal treatment of soman-poisoned mice was
evaluated. METHODS: The evaluation of the effect of pharmacological pretreatment
is based on the identification of changes of soman-induced toxicity that was
evaluated by the assessment of its LD50 value and its 95% confidence limit using
probitlogarithmical analysis of death occurring within 24 h after administration
of soman. RESULTS: 6-chlorotacrine was only able to markedly protect mice against
acute toxicity of soman. In addition, the pharmacological pretreatment with 6
chlorotacrine or compound 2 was able to increase the efficacy of antidotal
treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice.
The other newly prepared reversible inhibitors of acetylcholinesterase (7
phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not
influence the efficacy of antidotal treatment. CONCLUSION: These findings
demonstrate that pharmacological pretreatment of somanpoisoned mice can be
promising and useful in the case of administration of 6-chlorotacrine and partly
compound 2.
PMID- 28418833
TI - Willingness to Pay in Caregivers of Patients Affected by Schizophrenia.
AB - BACKGROUND: Schizophrenia is a debilitating disorder that often requires the
affected individual to receive care from a caregiver. Willingness to Pay (WTP)
technique allows a valuation of the health state preferences by assessing the
impact of the disease and translating it into monetary terms. AIMS OF THE STUDY:
The objective was to determine the WTP of schizophrenic patients' caregivers on a
hypothetical recovery scenario and correlate it to socio-demographic and clinical
characteristics, Knowledge of Disease, Quality of life and Burden of Disease.
METHODS: A convenience sample consecutively assessed 189 outpatients' caregivers
from Schizophrenia Program of Federal University of Sao Paulo. A single caregiver
was considered for each patient, taking into consideration their close
relationship and their direct involvement in the treatment. Open WTP
questionnaire for a hypothetical schizophrenia recovery scenario, KAST (Knowledge
of Disease), SF-6D (Quality of life) and ZBI-22 (Burden of Disease) scales were
applied. RESULTS: A monthly WTP mean value (SD) of US?USD 63.63 (111.88) was
found. The average value (SD) found was 12.96 (2.45) on KAST, 0.78 (0.08) on SF6D
and 29.91 (16.10) on ZARIT. Income, education, social class, knowledge of disease
and burden of caregiver were positively correlated to the WTP value. By linear
regression model, income and education remained significant. CONCLUSION:
Willingness to Pay (WTP) is a method that can be used to determine the strength
of preference of patients and caregivers for a recovery in schizophrenia. The
higher the income and education, the higher the willingness to pay. No clinical
characteristics of patients had a statistically significant relation to the value
the caregiver would pay. IMPLICATIONS FOR HEALTH POLICIES: WTP is a potentially
useful tool to determine values and health care preferences, and can be used for
the development of mental health policies. IMPLICATIONS FOR FURTHER RESEARCH:
Future research should be used to enhance WTP tool in mental health studies on
the impact of diseases, including schizophrenia.
PMID- 28418834
TI - Reduction in Costs after Treating Comorbid Panic Disorder with Agoraphobia and
Generalized Anxiety Disorder.
AB - BACKGROUND: Panic disorder with agoraphobia (PDA) and generalized anxiety
disorder (GAD) are impairing and costly disorders that are often misdiagnosed and
left untreated despite multiple consultations. These disorders frequently co
occur, but little is known about the costs associated with their comorbidity and
the impact of cognitive-behavioral therapy (CBT) on cost reduction. AIMS OF THE
STUDY: The first objective of this study was to assess the mental health-related
costs associated with the specific concomitance of PDA and GAD. The second aim
was to determine whether there is a reduction in direct and indirect mental
health-related costs following conventional CBT for the primary disorder only
(PDA or GAD) or combined CBT adapted to the comorbidity (PDA and GAD). METHODS: A
total of 123 participants with a double diagnosis of PDA and GAD participated in
this study. Direct and indirect mental health-related costs were assessed and
calculated from a societal perspective at the pre-test, the post-test, and the
three-month, six-month and one-year follow-ups. RESULTS: At the pre-test, PDA-GAD
comorbidity was found to generate a mean total cost of CADUSD 2,000.48 (SD = USD
2,069.62) per participant over a three-month period. The indirect costs were much
higher than the direct costs. Both treatment modalities led to significant and
similar decreases in all cost categories from the pre-test to the post-test. This
reduction was maintained until the one-year follow-up. DISCUSSION: Methodological
choices may have underestimated cost evaluations. Nonetheless, this study
supports the cost offset effects of both conventional CBT for primary PDA or GAD
and combined CBT for PDA-GAD comorbidity. IMPLICATIONS FOR HEALTHCARE PROVISION
AND USE: Treatment of comorbid and costly disorders with evidence-based
treatments such as CBT may lead to considerable economic benefits for society.
IMPLICATIONS FOR HEALTH POLICIES: Considering the limited resources of healthcare
systems, it is important to make choices that will lead to better accessibility
of quality services. The application of CBT for PDA, GAD or both disorders and
training mental health professionals in this therapeutic approach should be
encouraged. Additionally, it would be favorable for insurance plans to reimburse
employees for expenses associated with psychological treatment for anxiety
disorders. IMPLICATIONS FOR FURTHER RESEARCH: In addition to symptom reduction,
it would be of great pertinence to explore which factors can contribute to
reducing direct and indirect mental health-related costs.
PMID- 28418835
TI - Costs and Effectiveness of Treating Homeless Persons with Cocaine Addiction with
Alternative Contingency Management Strategies.
AB - BACKGROUND: Between 1990 and 2006 in Birmingham, Alabama USA, 4 separate
randomized controlled studies, called "Homeless 1" through "Homeless 4", treated
cocaine substance abuse among chronically homeless adults, largely black men,
many with non-psychotic mental health problems. The 4 studies had 9 treatment
arms that used various counseling methods plus, in some arms, the provision of
housing and work therapy usually with a contingent requirement of urine-test
verified abstinence from substances. Participants in the abstinent-contingent
arms who lapsed on abstinence were removed from housing and sent to an evening
public shelter from which they were daily transported to day treatment until they
returned to abstinence. AIMS OF THE STUDY: This paper compares the cost
effectiveness of the treatment arms. METHODS: Societal cost per participant (in
2014 dollars) for each arm is defined as direct treatment cost plus cost of jail
or hospital plus societal expense of public shelter use by lapsed participants.
An untreated Base Case is defined as 5 percent abstinence with 95 percent usage
of a public shelter. Incremental Cost Effectiveness Ratios (ICERs) for paired
arms are defined as the change in cost per participant divided by the change in
abstinence. Bootstrapping estimates confidence intervals. RESULTS: Average cost
per participant at the end of 6 months of active treatment in 7 arms with
comparable data ranged from USD 10,447 to USD 36,194 with corresponding average
weeks abstinent ranging from 6.1 to 15.3 out of a possible 26 weeks. In contrast,
the Base Case would cost USD 6,123 for 1.3 weeks of abstinence. Compared to the
Base Case, the least expensive "DT2" treatment has an ICER of USD 901 (95% CI =
USD 571 to USD 1,681) per additional week of abstinence and the most expensive
"CMP4" has an ICER of USD 2,147 (95% CI = USD 1,701 to USD 2,848). Additionally,
the Homeless 3 study found that the abstinent contingent housing (ACH3) treatment
compared to the Non Abstinent Contingent Housing (NAC3), analogous to "Housing
First", achieved better abstinence (12.1 v. 10 weeks) at higher average cost (USD
22,512 v. USD 17,541) yielding an ICER for this comparison of (USD 2,367, 95%
CI=USD -10,587 to USD 12,467). Similar results are found at 12 months (6 months
after active treatment). DISCUSSION: More intensive methods of counseling
improved abstinence but 4 of the 7 treatments were inefficient ("dominated").
Bootstrapping shows that results are sensitive to which individuals were randomly
assigned to each arm. A limitation of the analysis is that it does not consider
the full societal cost of lost wages, crime costs beyond jail expenses and
deterioration of neighborhood quality of life. Additionally, populations treated
by Housing First programs may differ from the Birmingham Homeless studies in the
severity of addiction or co-occuring psychological problems. IMPLICATIONS FOR
TREATMENT: The Homeless studies show that abstinent contingent safe housing with
counseling can substantially improve abstinence for homeless cocaine abusers.
Incremental costs rise sharply with more intensive counseling; modest programs of
counseling may be more cost effective in a stepped treatment strategy.
PMID- 28418836
TI - PERSPECTIVES: Accountability for Mental Health: The Australian Experience.
AB - BACKGROUND: Australia was one of the first countries to develop a national policy
for mental health. A persistent characteristic of all these policies has been
their reference to the importance of accountability. What does this mean exactly
and have we achieved it? Can Australia tell if anybody is getting better? AIMS OF
THE STUDY: To review accountability for mental health in Australia and question
whether two decades of Australian rhetoric around accountability for mental
health has been fulfilled. METHODS: This paper first considers the concept of
accountability and its application to mental health. We then draw on existing
literature, reports, and empirical data from national and state governments to
illustrate historical and current approaches to accountability for mental health.
We provide a content analysis of the most current set of national indicators. The
paper also briefly considers some relevant international processes to compare
Australia's progress in establishing accountability for mental health. RESULTS:
Australia's federated system of government permits competing approaches to
accountability, with multiple and overlapping data sets. A clear national
approach to accountability for mental health has failed to emerge. Existing data
focuses on administrative and health service indicators, failing to reflect
broader social factors which reveal quality of life. In spite of twenty years of
investment and effort Australia has been described as outcome blind, unable to
demonstrate the merit of USD 8bn spent on mental health annually. DISCUSSION AND
LIMITATIONS: While it may be prolific, existing administrative data provide
little outcomes information against which Australia can genuinely assess the
health and welfare of people with a mental illness. International efforts are
evolving slowly. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Even in high
income countries such as Australia, resources for mental health services are
constrained. Countries cannot afford to continue to invest in services or
programs that fail to demonstrate good outcomes for people with a mental illness
or are not value for money. IMPLICATIONS FOR HEALTH POLICIES: New approaches are
needed which ensure that chosen accountability indicators reflect national health
and social priorities. Such priorities must be meaningful to a range of
stakeholders and the community about the state of mental health. They must drive
an agenda of continuous improvement relevant to those most affected by mental
disorders. These approaches should be operable in emerging international
contexts. IMPLICATIONS FOR FURTHER RESEARCH: Australia must further develop its
approach to health accountability in relation to mental health. A limited set of
new preferred national mental health indicators should be agreed. These should be
tested, both domestically and internationally, for their capacity to inform and
drive quality improvement processes in mental health. CONCLUSION: Existing
systems of accountability are not fit for purpose, incapable of firing necessary
quality improvement processes. Supported by adequate resources, realistic targets
and a culture of openness, new accountability could drive real quality
improvement processes for mental health, facilitate jurisdictional comparisons in
Australia, and contribute to new efforts to benchmark mental health
internationally.
PMID- 28418837
TI - Rapamycin promotes differentiation increasing betaIII-tubulin, NeuN, and NeuroD
while suppressing nestin expression in glioblastoma cells.
AB - Glioblastoma cells feature mammalian target of rapamycin (mTOR) up-regulation
which relates to a variety of effects such as: lower survival, higher
infiltration, high stemness and radio- and chemo-resistance. Recently, it was
demonstrated that mTOR may produce a gene shift leading to altered protein
expression. Therefore, in the present study we administered different doses of
the mTOR inhibitor rapamycin to explore whether the transcription of specific
genes are modified. By using a variety of methods we demonstrate that rapamycin
stimulates gene transcription related to neuronal differentiation while
inhibiting stemness related genes such as nestin. In these experimental
conditions, cell phenotype shifts towards a pyramidal neuron-like shape owing
long branches. Rapamycin suppressed cell migration when exposed to fetal bovine
serum (FBS) while increasing the cell adhesion protein phospho-FAK (pFAK). The
present study improves our awareness of basic mechanisms which relate mTOR
activity to the biology of glioblastoma cells. These findings apply to a variety
of effects which can be induced by mTOR regulation in the brain. In fact, the
ability to promote neuronal differentiation might be viewed as a novel
therapeutic pathway to approach neuronal regeneration.
PMID- 28418839
TI - Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP
induced purinergic signalling and cell migration in human hepatocellular
carcinoma cells.
AB - Extracellular ATP-induced Ca2+ signalling is critical in regulating diverse
physiological and disease processes. Emerging evidence suggests high
concentrations of extracellular ATP in tumour tissues. In this study, we examined
the P2 receptor for ATP-induced Ca2+ signalling in human hepatocellular carcinoma
(HCC) cells. Fura-2-based measurements of the intracellular Ca2+ concentration
([Ca2+]i) showed that extracellular ATP induced an increase in the [Ca2+]i in
human HCC Huh-7 and HepG2 cells. NF546, a P2Y11 receptor agonist was equally
effective in inducing an increase in the [Ca2+]i. In contrast, agonists for the
P2X receptors (alphabetameATP and BzATP), P2Y1 receptor (MRS2365) or P2Y2
receptor (MRS2768) were ineffective. In addition, ATP/NF546-induced increases in
the [Ca2+]i were strongly inhibited by treatment with NF340, a P2Y11 receptor
antagonist. Immunofluorescent confocal imaging and western blotting analysis
consistently demonstrated the P2Y11 receptor expression in Huh-7 and HepG2 cells.
Transfection with P2Y11-specific siRNA attenuated the P2Y11 receptor protein
expression level and also reduced NF546-induced increase in the [Ca2+]i.
Importantly, immunohistochemistry revealed that the P2Y11 receptor was expressed
at very high level in human HCC tissues and, by contrast, it was barely detected
in normal liver tissues. Trans-well cell migration assay demonstrated that ATP
and NF546 induced concentration-dependent stimulation of Huh-7 cell migration.
Treatment with NF340 prevented ATP-induced stimulation of cell migration. Taken
together, our results show carcinoma-specific expression of the P2Y11 receptor
and its critical role in mediating ATP-inducing Ca2+ signalling and regulating
cell migration in human HCC cells.
PMID- 28418840
TI - Distinct MDCT imaging features to differential diagnosis of hepatic
paragonimiasis and small hepatocellular carcinoma.
AB - We used multi-row detector computed tomography (MDCT) to identify the
distinguishing characteristics of hepatic paragonimiasis and small hepatocellular
carcinoma lesions. We analyzed a cohort of 60 patients, of which 26 had hepatic
paragonimiasis and 34 with a small (<= 3cm) hepatocellular carcinoma. MDCT
detected 65 lesions that were retrospectively reviewed and analyzed based on
their imaging features. Both groups showed distinct MDCT imaging features that
could contribute to an accurate diagnosis. In the paragonimiasis group, 75%
(21/28) lesions were located in the hepatic subcapsular region, whereas only
10.8% (4/37) of lesions in the hepatocellular carcinoma group were subcapsular.
Most hepatic paragonimiasis lesions (57.1%; 16/28) also showed characteristic
tubular or tunnel features that were not present in hepatocellular carcinomas.
Further, 71.4% (20/28) paragonimiasis lesions were rim enhanced with irregular
tract-like non-enhanced internal areas with a characteristic target loop, while
94.6% (35/37) of small hepatocellular carcinoma lesions showed homogenous
enhancement in the arterial and venous phase. In addition, the period CT values
for hepatic paragonimiasis were less than those of hepatic carcinomas (P<0.001).
These clinically significant findings illustrate the diagnostic features that
enable one to distinguish hepatic paragonimiasis from small hepatocellular
carcinomas.
PMID- 28418841
TI - Circulating uric acid levels and subsequent development of cancer in 493,281
individuals: findings from the AMORIS Study.
AB - OBJECTIVES: Serum uric acid has been suggested to be associated with cancer risk.
We aimed to study the association between serum uric acid and cancer incidence in
a large Swedish cohort. RESULTS: A positive association was found between uric
acid levels and overall cancer risk, and results were similar with adjustment for
glucose, triglycerides and BMI. Hazard ratio (HR) for overall cancer for the 4th
quartile of uric acid compared to the 1st was 1.08 (95% CI: 1.05-1.11) in men and
1.12 (1.09 - 1.16) in women. Site-specific analysis showed a positive association
between uric acid and risk of colorectal, hepatobiliary, kidney, non-melanoma
skin, and other cancers in men and of head and neck and other cancers in women.
An inverse association was observed for pulmonary and central nervous system
(CNS) cancers in men and breast, lymphatic and haematological, and CNS
malignancies in women. MATERIALS AND METHODS: We included 493,281 persons aged 20
years and older who had a measurement of serum uric acid and were cancer-free at
baseline in the AMORIS study. Multivariable Cox proportional hazards regression
was used to investigate sex-specific quartiles of serum uric acid in relation to
cancer risk in men and women. Analysis was further adjusted for serum glucose,
triglycerides and, where available, BMI. Site-specific analysis was performed for
major cancers. CONCLUSIONS: Altered uric acid levels were associated with risk of
overall and some specific cancers, further indicating the potential role of uric
acid metabolism in carcinogenesis.
PMID- 28418842
TI - Effects of TLR-2/NF-kappaB signaling pathway on the occurrence of degenerative
knee osteoarthritis: an in vivo and in vitro study.
AB - The study aims to explore the effects of TLR-2/NF-kappaB signaling pathway on the
occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and
normal cartilage samples were collected from patients with degenerative knee OA
receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-kappaB
and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were
divided into control, IL-1beta, IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups.
MTT assay and flow cytometry were performed to determine proliferation and
apoptosis of the chondrocytes. Expressions of TLR-2, NF-kappaB and MMP-13 were
measured by Western blotting. ELISA was conducted to detect the expressions of
related inflammatory factors. The positive expressions of TLR, NF-kappaB and
MMP13 were associated with body mass index (BMI), family history, exercise, and
WOMAC scores of OA patients. Logistic regression analysis showed that OA
influencing factors were TLR, NF-kappaB, MMP13, BMI, family history and exercise.
Compared with normal chondrocytes, the expressions of TLR-2, NF-kappaB, MMP-13
and related inflammatory factors increased in degenerative knee OA. The
chondrocytes in the IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups showed lower
apoptosis rates than those in the IL-1beta group. Compared with the control
group, increased expressions of TLR-2, NF-kappaB, phosphorylated-NF-kappaB (p-NF
kappaB), MMP-13, IL-1, IL-6 and TNF-alpha were found in the IL-1beta group. In
the IL-1beta + anti-TLR-2 and IL-1beta + PDTC groups, decreased expressions of NF
kappaB, p-NF-kappaB, MMP-13, IL-1, IL-6 and TNF-alpha were found compared with
those in the IL-1beta group. TLR-2/NF-kappaB signaling pathway contributes to the
occurrence of degenerative knee OA.
PMID- 28418843
TI - CD24 Expression and differential resistance to chemotherapy in triple-negative
breast cancer.
AB - Breast cancer (BC) is a leading cause of cancer-related death in women. Adjuvant
systemic chemotherapies are effective in reducing risks of recurrence and have
contributed to reduced BC mortality. Although targeted adjuvant treatments
determined by biomarkers for endocrine and HER2-directed therapies are largely
successful, predicting clinical benefit from chemotherapy is more challenging.
Drug resistance is a major reason for treatment failures. Efforts are ongoing to
find biomarkers to select patients most likely to benefit from chemotherapy.
Importantly, cell surface biomarkers CD44+/CD24- are linked to drug resistance in
some reports, yet underlying mechanisms are largely unknown. This study focused
on the potential role of CD24 expression in resistance to either docetaxel or
doxorubicin in part by the use of triple-negative BC (TNBC) tissue microarrays.
In vitro assays were also done to assess changes in CD24 expression and
differential drug susceptibility after chemotherapy. Further, mouse tumor
xenograft studies were done to confirm in vitro findings. Overall, the results
show that patients with CD24-positive TNBC had significantly worse overall
survival and disease-free survival after taxane-based treatment. Also, in vitro
cell studies show that CD44+/CD24+/high cells are more resistant to docetaxel,
while CD44+/CD24-/low cells are resistant to doxorubicin. Both in vitro and in
vivo studies show that cells with CD24-knockdown are more sensitive to docetaxel,
while CD24-overexpressing cells are more sensitive to doxorubicin. Further,
mechanistic studies indicate that Bcl-2 and TGF-betaR1 signaling via ATM-NDRG2
pathways regulate CD24. Hence, CD24 may be a biomarker to select
chemotherapeutics and a target to overcome TNBC drug resistance.
PMID- 28418844
TI - Loss of tumour-specific ATM protein expression is an independent prognostic
factor in early resected NSCLC.
AB - Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity.
In response to DNA double-strand breaks, ATM phosphorylates downstream proteins
involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we
investigate the frequency, and influence of ATM deficiency on outcome, in early
resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165
formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed
at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were
analyzed for ATM expression using quantitative fluorescence immunohistochemistry.
Both malignant cell-specific ATM expression and the ratio of ATM expression
within malignant tumour cells compared to that in the surrounding tumour stroma,
defined as the ATM expression index (ATM-EI), were measured and correlated with
clinical outcome. ATM loss was identified in 21.8% of patients, and was
unaffected by clinical pathological variables. Patients with low ATM-EI tumours
had worse survival outcomes compared to those with high ATM-EI (p < 0.01). This
effect was pronounced in stage II/III patients, even after adjusting for other
clinical co-variates (p < 0.001). Additionally, we provide evidence that ATM
deficient patients may derive greater benefit from guideline-recommended adjuvant
chemotherapy following surgical resection. Taken together, these results indicate
that ATM loss seems to be an early event in NSCLC carcinogenesis and is an
independent prognostic factor associated with worse survival in stage II/III
patients.
PMID- 28418845
TI - Preclinical development of G1T38: A novel, potent and selective inhibitor of
cyclin dependent kinases 4/6 for use as an oral antineoplastic in patients with
CDK4/6 sensitive tumors.
AB - Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic
strategy for the treatment of estrogen receptor positive (ER+) breast cancer.
Although efficacious, current treatment regimens require a dosing holiday due to
severe neutropenia potentially leading to an increased risk of infections, as
well as tumor regrowth and emergence of drug resistance. Therefore, a next
generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent
tumors while minimizing neutropenia could reduce both the need for treatment
holidays and the risk of inducing drug resistance.Here, we describe the
preclinical characterization and development of G1T38; a novel, potent,
selective, and orally bioavailable CDK4/6 inhibitor. In vitro, G1T38 decreased
RB1 (RB) phosphorylation, caused a precise G1 arrest, and inhibited cell
proliferation in a variety of CDK4/6-dependent tumorigenic cell lines including
breast, melanoma, leukemia, and lymphoma cells. In vivo, G1T38 treatment led to
equivalent or improved tumor efficacy compared to the first-in-class CDK4/6
inhibitor, palbociclib, in an ER+ breast cancer xenograft model. Furthermore,
G1T38 accumulated in mouse xenograft tumors but not plasma, resulting in less
inhibition of mouse myeloid progenitors than after palbociclib treatment. In
larger mammals, this difference in pharmacokinetics allowed for 28 day continuous
dosing of G1T38 in beagle dogs without producing severe neutropenia. These data
demonstrate G1T38 has unique pharmacokinetic and pharmacodynamic properties,
which result in high efficacy against CDK4/6 dependent tumors while minimizing
the undesirable on-target bone marrow activity, thus potentially allowing G1T38
to be used as a continuous, daily oral antineoplastic agent.
PMID- 28418846
TI - Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery
for brain tumor therapy.
AB - Convection-enhanced delivery (CED) is a promising technique for infusing a
therapeutic agent through a catheter with a pressure gradient to create bulk flow
for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd
DTPA) is the most commonly applied surrogate agent for predicting drug
distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides
only a short observation duration, and concurrent infusion provides an indirect
measure of the exact drug distribution. In this study, we propose using
microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a
drug-carrying vehicle to directly monitor the infused drug. Results show that
microbubbles can provide excellent detectability through MRI relaxometry and
accurately represent drug distribution during CED infusion. Compared with the
short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended
observation period of up to 12 hours. Moreover, microbubbles provide a
sufficiently high drug payload, and glioma mice that underwent a CED infusion of
microbubbles carrying doxorubicin presented considerable tumor growth suppression
and a significantly improved survival rate. This study recommends microbubbles as
a new theranostic tool for CED procedures.
PMID- 28418847
TI - Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT
expression and MPF activity.
AB - If no fertilization occurs at an appropriate time after ovulation, oocyte quality
deteriorates rapidly as a process called postovulatory aging. Because the
postovulatory aging of oocytes has detrimental effects on embryo development and
offspring, many efforts have been made to prevent oocyte aging. Here we showed
that quercetin prevented the decline in oocyte quality during postovulatory aging
of oocytes. Quercetin treatment reduced aging-induced morphological changes and
reactive oxygen species accumulation. Moreover, quercetin attenuated the aging
associated abnormalities in spindle organization and mitochondrial distribution,
preventing decrease of SIRT expression and histone methylation. Quercetin also
ameliorated the decrease in maturation-promoting factor activity and the onset of
apoptosis during postovulatory aging. Furthermore, quercetin treatment during
postovulatory aging improves early embryo development. Our results demonstrate
that quercetin relieves deterioration in oocyte quality and improves subsequent
embryo development.
PMID- 28418849
TI - Oncologic and obstetrical outcomes with fertility-sparing treatment of cervical
cancer: a systematic review and meta-analysis.
AB - OBJECTIVE: The objectives of this study were to evaluate the rates of recurrence,
survival and pregnancy, and characterize pregnancy outcomes of early-stage
cervical cancer(eCC) treated with fertility-sparing methods such as cervical
conization (CON) and radical trachelectomy(RT) with or without pelvic
lymphadenectomy. STUDY DESIGN: This was a meta-analysis of observational studies
analyzed by a random-effects model and a meta-regression to assess heterogeneity.
RESULTS: Sixty observational studies encompassing 2,854 patients were included;
17 of which evaluated CON and 43 RT. Three hundred and seventy-five patients were
included in the CON group: 176(46.9%) stage IA1 and 167(44.5%) stage IB1. In the
RT group, 2479 cases were included: 143(6.0%) stage IA1, 299(12.1%) stage IA2,
1987(79.9%) stage IB1. CON was performed in 347(92.5%) cases, resulting in a
recurrence rate of 0.4%(95%CI: 0.0%-1.4%), a death rate of 0%(0%-0%), a pregnancy
rate of 36.1%(26.4%-46.2%), a spontaneous abortion rate of 14.8%(9.3%-21.2%) and
a preterm delivery rate of 6.8%(1.5%-15.5%). For the RT group, 2273(91.7%)
underwent successful surgeries with a recurrence rate of 2.3%(1.3%-3.4%),a death
rate of 0.7%(0.3%-1.1%), a pregnancy rate of 20.5%(16.8%-24.5%), a spontaneous
abortion rate of 24.0%(18.8%-29.6%) and a preterm delivery rate of 26.6%(19.6%
34.2%). From a subgroup analysis, the recurrence rates for stage IA tumors
treated with CON and RT were 0.4%(0.0%-1.9%) and 0.7%(0.0%-2.3%), respectively;
and for stage IB were 0.6%(0.0%-2.7%) and 2.3%(0.9%-4.1%). CONCLUSION: Fertility
sparing treatment including CON or RT for eCC is feasible and carefully selected
women can preserve fertility and achieve pregnancy resulting in live births. CON
seems to result in better pregnancy outcomes than RT with similar rates of
recurrence and mortality.
PMID- 28418851
TI - High serum lactate dehydrogenase predicts an unfavorable outcome in Chinese
elderly patients with multiple myeloma.
AB - There is significant heterogeneity among multiple myeloma (MM) patients with the
survival duration varying greatly from a few months to several years. This study
retrospectively analyzed serum lactate dehydrogenase (LDH) in 105 cases of newly
diagnosed elderly MM patients to investigate its value for outcome prediction.
Serum LDH concentrations were evaluated prior to induction therapy. Prognostic
analyses were carried out based on LDH levels and patients' other clinical data.
We also applied the recently proposed Revised International Staging System (R
ISS) to 70 patients with the available data. Of all the patients, elevated serum
LDH levels (>=271U/L) were observed in 13.3% (14 out of 105) patients at
diagnosis. Compared with normal LDH group, high LDH group had significantly
shorter overall survival (OS) (15.5 vs. 52.5 months, p = 0.002) and median
progression free survival (PFS) (12.0 vs. 24 months, p = 0.030), as well as 2
year OS rate (20% vs. 81%, p < 0.001) and PFS rate (22% vs. 44%, p = 0.005). A
multivariate analysis identified high LDH as a unique independent adverse
prognostic parameter for both OS and PFS. In addition, there were significant
differences between R-ISS II and R-ISS III patients in both median OS (52.5 vs.
15.5 months, p < 0.001) and PFS (23 vs. 7.5 months, p = 0.004). Furthermore, high
LDH was a unique independent adverse indicator for overall response rate (ORR)
and early death in elderly MM patients. These results identified LDH as an
unfavorable prediction for the outcome of Chinese elderly patients with MM. R-ISS
based on LDH is superior to ISS in prognostic assessment.
PMID- 28418852
TI - Structural homologies between phenformin, lipitor and gleevec aim the same
metabolic oncotarget in leukemia and melanoma.
AB - Phenformin's recently demonstrated efficacy in melanoma and Gleevec's
demonstrated anti-proliferative action in chronic myeloid leukemia may lie within
these drugs' significant pharmacokinetics, pharmacodynamics and structural
homologies, which are reviewed herein. Gleevec's success in turning a fatal
leukemia into a manageable chronic disease has been trumpeted in medical,
economic, political and social circles because it is considered the first
successful targeted therapy. Investments have been immense in omics analyses and
while in some cases they greatly helped the management of patients, in others
targeted therapies failed to achieve clinically stable recurrence-free disease
course or to substantially extend survival. Nevertheless protein kinase
controlling approaches have persisted despite early warnings that the targeted
genomics narrative is overblown. Experimental and clinical observations with
Phenformin suggest an alternative explanation for Gleevec's mode of action. Using
13C-guided precise flux measurements, a comparative multiple cell line study
demonstrated the drug's downstream impact on submolecular fatty acid processing
metabolic events that occurred independent of Gleevec's molecular target.
Clinical observations that hyperlipidemia and diabetes are both reversed in mice
and in patients taking Gleevec support the drugs' primary metabolic targets by
biguanides and statins. This is evident by structural data demonstrating that
Gleevec shows pyridine- and phenyl-guanidine homology with Phenformin and
identical phenylcarbamoyl structural and ligand binding homology with Lipitor.
The misunderstood mechanism of action of Gleevec is emblematic of the pervasive
flawed reasoning that genomic analysis will lead to targeted, personalized
diagnosis and therapy. The alternative perspective for Gleevec's mode of action
may turn oncotargets towards metabolic channel reaction architectures in leukemia
and melanoma, as well as in other cancers.
PMID- 28418854
TI - Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a
meta-analysis.
AB - The BRCA2 gene plays an important role in cancer carcinogenesis, and
polymorphisms in this gene have been associated with cancer risk. The BRCA2
rs144848 polymorphism has been associated with several cancers, but results have
been inconsistent. In the present study, a meta-analysis was performed to assess
the association between the rs144848 polymorphism and cancer risk. Literature was
searched from the databases of PubMed, Embase and Google Scholar before April
2016. The fixed or random effects model was used to calculate pooled odd ratios
on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup
analysis and publication bias assessment were also performed using STATA 11.0
software according to Preferred Reporting Items for Systematic Reviews and Meta
Analyses 2009. A total of 40 relevant studies from 30 publications including
34,911 cases and 48,329 controls were included in the final meta-analysis. Among
them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non
Hodgkin lymphoma, and the remaining six studies examined various other cancers.
The meta-analysis results showed that there were significant associations between
the rs144848 polymorphism and cancer risk in all genetic models. Stratified by
cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma.
Stratified by study design, the allele model was associated with breast cancer
risk in population-based studies. The meta-analysis suggests that the BRCA2
rs144848 polymorphism may play a role in cancer risk. Further well-designed
studies are warranted to confirm these results.
PMID- 28418855
TI - A review and outlook in the treatment of osteosarcoma and other deep tumors with
photodynamic therapy: from basic to deep.
AB - Photodynamic therapy, one of the most promising minimally invasive treatments,
has received increasing focus in tumor therapy research, which has been widely
applied in treating superficial tumors. Three basic factors - photosensitizer,
the light source, and oxidative stress - are responsible for tumor cell
cytotoxicity. However, due to insufficient luminous flux and peripheral tissue
damage, the utilization of photodynamic therapy is facing a huge limitation in
deep tumor therapy. Osteosarcoma is the typical deep tumor, which is the most
commonly occurring malignancy in children and adolescents. Despite developments
in surgery, high risks of the amputation still threatens the health of
osteosarcoma patients. In this review, we summarize recent developments in the
field of photodynamic therapy and specifically PDT research in OS treatment
modalities. In addition, we also provide some novel suggestions, which could
potentially be a breakthrough in PDT-induced OS therapies. PDT has the potential
to become an effective therapy while the its limitations still present when
applied on the treatment of OS or other types of deep tumors. Thus, more
researches and studies in the field are required.
PMID- 28418856
TI - Low-density lipoprotein receptor-related protein 6 is a novel coreceptor of
protease-activated receptor-2 in the dynamics of cancer-associated beta-catenin
stabilization.
AB - Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the
molecular machinery of PAR2-instigated tumors remains to be elucidated. We show
that PAR2 is a potent inducer of beta-catenin stabilization, a core process in
cancer biology, leading to its transcriptional activity. Novel association of low
density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds
(Fz), with PAR2 takes place following PAR2 activation. The association between
PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence
resonance energy transfer (BRET), and confocal microscopy analysis. The
association was further supported by ZDOCK protein-protein server. PAR2-LRP6
interaction promotes rapid phosphorylation of LRP6, which results in the
recruitment of Axin. Confocal microscopy of PAR2-driven mammary gland tumors in
vivo, as well as in vitro confirms the association between PAR2 and LRP6. Indeed,
shRNA silencing of LRP6 potently inhibits PAR2-induced beta-catenin
stabilization, demonstrating its critical role in the induced path. We have
previously shown a novel link between protease-activated receptor-1 (PAR1) and
beta-catenin stabilization, both in a transgenic (tg) mouse model with
overexpression of human PAR1 (hPar1) in the mammary glands, and in cancer
epithelial cell lines. Unlike in PAR1-Galpha13 axis, both Galpha12 and Galpha13
are equally involved in PAR2-induced beta-catenin stabilization. Disheveled (DVL)
is translocated to the cell nucleus through the DVL-PDZ domain. Collectively, our
data demonstrate a novel PAR2-LRP6-Axin interaction as a key axis of PAR2-induced
beta-catenin stabilization in cancer. This newly described axis enhances our
understanding of cancer biology, and opens new avenues for future development of
anti-cancer therapies.
PMID- 28418857
TI - Multi-factorial modulation of colorectal carcinoma cells motility - partial
coordination by the tetraspanin Co-029/tspan8.
AB - Colorectal carcinoma cells Isreco1 display an ability to migrate controlled by a
complex set of signals issued from the membrane. By comparing cells infected by
mycoplasmas and mycoplasmas free cells, we have established that basal 2D
migration is dependent on a double signal mediated by the collagen receptors
integrins alpha1/2 and the Toll-Like receptor TLR2. The signal issued from
mycoplasmas can be replaced by a TLR2 ligand and the functional effect is
neutralized by silencing of MyD88. Following previous observation that
downregulation of E-cadherin/p120 catenin increases cell motility, we now report
that EGFR or CD44 inhibition have a similar effect on cell motility that is
restricted to tetraspanin Co-029/tspan8 transduced IsrecoI cells (Is1-Co029). The
modulation of cell migration linked to EGFR or CD44 can be neutralized by
antagonizing Co-029 with the mAb Ts29.1 or by RNA interference. Altogether these
data point to a crucial role of Co-029 in the modulation of colon cancer cell
motility which could be related to the protumoral effect reported for this
tetraspanin. Among surface molecules able to mediate Co-029 function, E-cadherin,
EGFR and CD44 appear as likely candidates.
PMID- 28418858
TI - The miR-124-p63 feedback loop modulates colorectal cancer growth.
AB - Among the diverse co-regulatory relationships between transcription factors (TFs)
and microRNAs (miRNAs), feedback loops have received the most extensive research
attention. The co-regulation of TFs and miRNAs plays an important role in
colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two
isoforms of p63, TAp63 and DeltaNp63, via iASPP, while p63 modulates signal
transducers and activators of transcription 1 (STAT1) expression by targeting miR
155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124.
Taken together, these results reveal a feedback loop between miRNAs and TFs. This
feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and DeltaNp63,
which are essential for CRC growth. Moreover, this feedback loop is perturbed in
human colon carcinomas, which suggests that the manipulation of this microRNA-TF
feedback loop has therapeutic potential for CRC.
PMID- 28418859
TI - Serum metabolomics differentiating pancreatic cancer from new-onset diabetes.
AB - To establish a screening strategy for pancreatic cancer (PC) based on new-onset
diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the
metabolic pathways associated with PC related DM were performed. Serum samples
from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM
were examined by liquid chromatography-mass spectrometry. Data were analyzed
using principal components analysis (PCA) and orthogonal projection to latent
structures (OPLS) of the most significant metabolites. The diagnostic model was
constructed using logistic regression analysis. Metabolic pathways were analyzed
using the web-based tool MetPA. PC patients with NO-DM were older and had a lower
BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of
patients with PC and NO-DM were significantly different from those of patients
with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were
identified by the OPLS model. The logistic regression model using a panel of two
metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high
sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic
pathways associated with PC related DM were valine, leucine and isoleucine
biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid
metabolism. In conclusion, screening for PC based on NO-DM using serum
metabolomics in combination with clinic characteristics and CA19-9 is a potential
useful strategy. Several metabolic pathways differed between PC related DM and
type 2 DM.
PMID- 28418860
TI - Targeting the overexpressed ROC1 induces G2 cell cycle arrest and apoptosis in
esophageal cancer cells.
AB - Recent reports showed that regulator of Cullins-1 (ROC1) play an important role
in tumor progression in a tumor-specific manner. However, the role and mechanism
of ROC1 in esophageal cancer remains elusive. Here we demonstrated that ROC1 was
overexpressed in esophageal squamous cell carcinomas, which was positive
associated with poor prognosis of esophageal cancer patients. ROC1 knockdown
significantly inhibited the growth of esophageal cancer cells in vitro and in
vivo. Mechanistically, ROC1 silencing induced G2 cell cycle arrest and triggered
apoptosis by accumulating the pro-apoptotic protein NOXA. Consistently, the
downregulation of NOXA expression via siRNA substantially attenuated apoptosis
induced by ROC1 silencing. These findings suggest that ROC1 is an appealing drug
target for esophageal cancer.
PMID- 28418861
TI - Brain-derived neurotrophic factor involved epigenetic repression of UGT2B7 in
colorectal carcinoma: A mechanism to alter morphine glucuronidation in tumor.
AB - Uridine diphosphate-glucuronosyltransferase (UGT) 2B7, as one of significant drug
enzymes, is responsible on the glucuronidation of abundant endobiotics or
xenobiotics. We here report that it is markedly repressed in the tumor tissues of
colorectal carcinoma (CRC) patients. Accordingly, morphine in CRC cells will
stimulate the expression of its main metabolic enzyme, UGT2B7 during tolerance
generation by activating the positive signals in histone 3, especially for
trimethylated lysine 27 (H3K4Me3) and acetylated lysine 4 (H3K27Ac). Further
study reveals that brain-derived neutrophilic factor (BDNF), a secretory
neurotrophin, enriched in CRC can interact and inhibit UGT2B7 by primarily
blocking the positive signals of H3K4Me3 as well as activating H3K27Ac on the
promoter region of UGT2B7. Meanwhile, BDNF repression attributes to the
sensitizations of main core factors in poly-comb repressive complex (PRC) 1
rather than PRC2 as the reason of the depression of SUZ12 in the later complex.
Besides that, the productions of two main morphine glucuronides are both
increased in the BDNF deficient or TSA and BIX-01294 treated morphine tolerance
like HCT-116 cells. On the same condition, active metabolite, morphine-6
glucuronide (M6G) was accumulated more than inactive M3G. Our findings imply that
enzymatic activity enhancement and substrate regioselective catalysis alteration
of UGT2B7 may release morphine tolerance under the cure of tumor-induced pain.
PMID- 28418862
TI - Niclosamide is a potential therapeutic for familial adenomatosis polyposis by
disrupting Axin-GSK3 interaction.
AB - The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and
cancer progression, and canonical Wnt signaling tightly controls Snail, a key
transcriptional repressor of EMT. While the suppression of canonical Wnt
signaling and EMT comprises an attractive therapeutic strategy, molecular targets
for small molecules reverting Wnt and EMT have not been widely studied.
Meanwhile, the anti-helminthic niclosamide has been identified as a potent
inhibitor of many oncogenic signaling pathways although its molecular targets
have not yet been clearly identified. In this study, we show that niclosamide
directly targets Axin-GSK3 interaction, at least in part, resulting in
suppression of Wnt/Snail-mediated EMT. In vitro and in vivo, disruption of Axin
GSK3 complex by niclosamide induces mesenchymal to epithelial reversion at nM
concentrations, accompanied with suppression of the tumorigenic potential of
colon cancer. Niclosamide treatment successfully attenuates Snail abundance while
increasing E-cadherin abundance in xenograft tumor. Notably, oral administration
of niclosamide significantly suppressed adenoma formation in an APC-MIN mice
model, indicating that niclosamide is an effective therapeutic for familial
adenomatosis polyposis (FAP) patients. In this study, we identified a novel
target to control the canonical Wnt pathway and Snail-mediated EMT program, and
discovered a repositioned therapeutics for FAP patients.
PMID- 28418863
TI - GALNT14 genotype as a response predictor for concurrent chemoradiotherapy in
advanced esophageal squamous cell carcinoma.
AB - Esophageal squamous cell carcinoma is an aggressive cancer. We investigated
genetic response predictors for patients with advanced esophageal squamous cell
carcinoma receiving concurrent chemoradiotherapy. A cohort of 108 patients was
recruited. Survival analysis showed that lower esophageal location of tumor, more
advanced metastasis stage, and longer length of tumor were associated with poorer
overall survival (adjusted P = 0.001, < 0.001, and 0.045, respectively), while
the presence of complete/partial response to concurrent chemoradiotherapy was
independently associated with better overall survival (adjusted P < 0.001). The
GALNT14-rs9679162 "GG" genotype was associated with a lower rate of response (P =
0.014). Multivariate Cox-proportional hazards models also showed that the "GG"
genotype was associated with a longer time to complete/partial response (adjusted
P = 0.022), independent of leukocyte counts and gender. In conclusion, the
presence of a complete/partial response to chemoradiotherapy was critical for
advanced esophageal squamous cell carcinoma patients to achieve better overall
survival. The GALNT14-rs9679162 "GG" genotype was associated with a longer time
to complete/partial response of concurrent chemoradiotherapy.
PMID- 28418864
TI - Bone marrow-derived mesenchymal stem cells overexpressing MiR-21 efficiently
repair myocardial damage in rats.
AB - OBJECTIVE: We investigated the ability of bone marrow derived mesenchymal stem
cells (BMSCs) overexpressing microRNA-21 (miR-21) to repair cardiac damage
induced by anthracyclines in rats. METHODS: Sprague-Dawley (SD) rats of 2~3 weeks
old were selected to isolate and culture BMSCs. A lentivirus harboring pLVX-miR
21 was generated and transfected into rat BMSCs. The rats were assigned into an
untreated negative control group, and groups injected with adriamycin alone or
with adriamycin followed by BMSCs, pLVX-BMSCs or pLVX-miR-21-BMSCs (n = 10 each).
Proliferation and migration of cells were detected by cholecystokinin-8 (CCK- 8)
and transwell. MiR-21 expression, mRNA expressions of B cell lymphoma 2 (Bcl2),
BAX (BCL-2-associated X protein) and vascular endothelial growth factor (VEGF)
were tested by qRT-PCR. Western blotting was applied to detect protein
expressions of Bcl-2, Bax and VEGF. RESULTS: Using CCK- 8 and transwell assays,
we found that pLVX-miR-21-BMSCs, which overexpressed miR-21, exhibited greater
proliferation and migration than untransfected BMSCs or pLVX-BMSCs. Ultrasonic
cardiograms and immunohistochemical analysis demonstrated that among the five
groups, the pLVX-miR-21-BMSC group exhibited the most improved heart function and
enhanced angiogenesis. Moreover, the pLVX-miR-21-BMSC group showed enhanced
expression of Bcl-2, VEGF and Cx43 and reduced expression of Bax, BNP and
troponin T. CONCLUSION: These findings suggest miR-21 overexpression enhanced the
proliferation, invasiveness and differentiation of BMSCs as well as expression of
key factors (Bcl-2, VEGF and Bax) essential for repairing the cardiac damage
induced by anthracyclines and restoring heart function.
PMID- 28418865
TI - Anti-helminthic niclosamide inhibits Ras-driven oncogenic transformation via
activation of GSK-3.
AB - Despite the importance of Ras oncogenes as a therapeutic target in human cancer,
their 'undruggable' tertiary structures limit the effectiveness of anti-Ras
drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase
kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent
degradation. In the accompanying report, we show that the anti-helminthic
niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer
cells, with reversion of Snail-mediated epithelial-mesenchymal transition. In
this study, we report that niclosamide effectively suppresses Ras and nuclear
NFAT activities regardless of the mutational status of Ras at nM levels.
Mechanistically, niclosamide increased endogenous GSK-3 activity, shortening the
half-life of mutant Ras. Further, niclosamide activates Raf-1 kinase inhibitory
protein, a downstream target of Snail repressor. Niclosamide treatment attenuates
Ras-induced oncogenic potential in vitro and in vivo. These findings provide a
clinically available repositioned Ras inhibitor as well as a novel strategy for
inhibiting the Ras via GSK-3.
PMID- 28418866
TI - Investigation of hypoxia conditions using oxygen-enhanced magnetic resonance
imaging measurements in glioma models.
AB - The objective of this study was to determine whether using oxygen-enhanced
magnetic resonance imaging (OE-MRI) to assess hypoxia is feasible and whether
historical measurements, pO2 changes, and percentage of signal intensity changes
(PSIC) are correlated in an animal model of glioma. A total of 25 Sprague-Dawley
rats were used to establish C6 brain or subcutaneous glioma model. Nine rats with
brain gliomas underwent OE-MRI followed by histopathologic analysis to assess
microvessel density and hypoxia. Another 11 rats were underwent OE-MRI and were
followed for a survival analysis. Time-T1-weighted MR signal intensity (SI)
curves and PSIC maps were derived from the OE-MRI data. High-regions of interests
(ROI-h; PSIC > 10%) and low-ROIs (ROI-l; PSIC < 10%) were defined on the PSIC
maps. To validate the PSIC map for identifying tumor hypoxia, we subjected an
additional 5 rats with subcutaneous glioma to OE-MRI and pO2 measurements. All
tumors showed regional heterogeneity on the PSIC maps. For the brain tumors, the
time-SI curves for the ROIs-h showed a greater increase in SI than those for the
ROIs-l did. The percentage of tumor area with a low PSIC was significantly
correlated with the percentage of hypoxia staining and necrosis (r =0.71;
P<0.05). ROIs with a higher PSIC typically had more vessels (r=0.88; P<0.05). A
significant difference in survival was shown (log-rank P = 0.035). The time-pO2
curves of the subcutaneous tumors were similar to the time-SI curves. PSIC was
significantly correlated with pO2 changes (r =0.82; P<0.05). These findings
suggest that OE-MRI measurements can be used to assess hypoxia in C6 glioma
models. In these models, the PSIC value was correlated with survival, indicating
that PSIC could serve as a prognostic marker for glioma.
PMID- 28418868
TI - GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and
its expression is associated with poorer prognosis.
AB - Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub
population of cancer cells that are endowed with higher tumor-initiating ability,
self-renewal ability and differentiation ability. CSCs/CICs could be isolated as
high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer
samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh
cells and investigated the molecular aspects. ALDH1high cells showed greater
sphere-forming ability and higher tumor-initiating ability in immune-deficient
mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in
ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate
receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in
ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene
knockdown by siRNAs decreased the sphere-forming ability and invasion ability,
whereas GRIK2 overexpression increased the sphere-forming ability, invasion
ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance
of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2
and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma
cases. The findings indicate that GRIK2 has a role in the maintenance of
urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers
for urinary tract carcinomas.
PMID- 28418867
TI - Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1,
CLIP4 and MSC DNA methylation in endoscopic biopsies.
AB - Clinically useful molecular tools to triage gastric cancer patients are not
currently available. We aimed to develop a molecular tool to predict gastric
cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer
clinics in low resource settings.We discovered and validated a DNA methylation
biomarker panel in endoscopic samples obtained from 362 patients seen between
2004 and 2009 in three high-risk gastric cancer clinics in Lima, Peru, and
validated it in 306 samples from the Cancer Genome Atlas project ("TCGA").
Global, epigenome wide and gene-specific DNA methylation analyses were used in a
Phase I Biomarker Development Trial to identify a continuous biomarker panel that
combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation
levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between
the GDMI and histological progression to gastric cancer, when comparing gastritis
patients without metaplasia (mean = 5.74, 95% CI, 4.97-6.50), gastritis patients
with metaplasia (mean = 4.81, 95% CI, 3.77-5.84), and gastric cancer cases (mean
= 3.38, 95% CI, 2.82-3.94), respectively (p < 0.0001). Promoter methylation of
IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001),
is also associated with increasing severity from gastritis with no metaplasia to
gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4,
ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful
molecular tools for gastric cancer risk stratification in endoscopic biopsies.
PMID- 28418869
TI - Development of a Taiwan cancer-related fatigue cognition questionnaire:
reliability and validity.
AB - PURPOSE: We prospectively designed a Taiwan cancer-related fatigue cognition
questionnaire, version 1.0 (TCRFCQ-V1.0), for Taiwanese patients with cancer and
investigated the reliability and validity of this questionnaire. RESULTS: The
completion rate of the TCRFCQ-V1.0 was high (97% of the patients completed all
items), and the rate of missing data was low (0.2%-1.1% for each item). Moreover,
the Cronbach alpha value was 0.889. We eliminated 5 items because their
respective Cronbach alpha values were higher than the total mean value of
Cronbach's alpha. Overall, the TCRFCQ-V1.0 had adequate Cronbach alpha
coefficients (range, from 0.882 to 0.889). In addition, the results of Bartlett's
test were significant (chi-squared, 2390.11; p < 0.001), indicating the
appropriateness of factor analysis. Sampling adequacy was confirmed by the Kaiser
Meyer-Olkin statistic of 0.868. Through exploratory factor analysis, we
identified 6 factors with eigenvalues of > 1, and the scree plot indicated no
flattening factors. Overall, 28 items achieved a factor loading of >= 0.55.
MATERIALS AND METHODS: We enrolled patients with cancer who were aged > 18 years,
had received a pathological diagnosis of cancer, and had undergone cancer
treatments such as surgery, chemotherapy, radiotherapy, or concurrent
chemoradiotherapy at a single institute in Taiwan. Of the identified 167 eligible
patients, 161 (96.4%) were approached. Of these patients, 6 (7.2%) declined to
participate and 155 (92.8%) were interviewed. The initial 43 items in the TCRFCQ
V1.0 were assessed for ceiling and floor effects. CONCLUSIONS: The TCRFCQ-V1.0 is
a reliable and valid instrument for measuring CRF cognition in Taiwanese patients
with cancer.
PMID- 28418872
TI - Overexpression of Fli-1 in astrocytoma is associated with poor prognosis.
AB - BACKGROUND: Astrocytoma, a common and highly malignant type of brain tumor, is
associated with poor overall survival despite advances in surgical treatment,
radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been
shown to increase cellular proliferation and tumorigenesis in many types of
cancer; however, previous reports have not described a correlation between
clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to
elucidate the clinical role of Fli-1 in astrocytoma. RESULTS: High-level of Fli-1
protein expression was significantly association with World Health Organization
(WHO) high grade and poor prognosis. A multivariate analysis revealed that the
WHO grade and Fli-1 protein expression were independent factor of prognostic
factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited
proliferation, migration, and invasion and led to the downregulation of Ki-67,
VEGF, and cyclin D1 expression in the astrocytoma cells. MATERIALS AND METHODS:
Fli-1 protein expression in astrocytoma tissue samples were detected via
immunohistochemistry, and potential correlations between clinical parameters and
Fli-1 expression were assessed in patients with astrocytoma. Additionally,
proliferation, invasion, and migration assays of astrocytoma cell lines were
conducted to evaluate the effects of short interfering RNA (siRNA) on these
processes; in addition, these cells were subjected to western blotting to detect
the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1. CONCLUSION: Fli-1
shows promise as a potential prognostic biomarker and therapeutic molecular
target for astrocytoma patients.
PMID- 28418870
TI - Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal
cancers: a systematic review and meta-analysis.
AB - An accurate, time efficient, and inexpensive prognostic indicator is needed to
reduce cost and assist with clinical decision making for cancer management. The
neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing,
has been explored in a variety of cancers. We sought to determine its prognostic
value in gastrointestinal cancers and performed a meta-analysis of published
studies using the Meta-analysis Of Observational Studies in Epidemiology
guidelines. Included were randomized control trials and observational studies
that analyzed humans with gastrointestinal cancers that included NLR and hazard
ratios (HR) with overall survival (OS), disease-free survival (DFS), progression
free survival (PFS), and/or cancer-specific survival (CSS).We analyzed 144
studies comprising 45,905 patients, two-thirds of which were published after
2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate
models were 3.4, 3.0, 5.0 (+/-IQR 2.5-5.0), respectively. Overall, NLR greater
than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P <
0.001). This association was observed in all subgroups based on tumor site,
stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70
(95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83
(95% CI, 1.50-2.23, P < 0.001), respectively.Available evidence suggests that NLR
greater than the cutoff reduces OS, independent of geographic location,
gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS
also have worse outcomes with elevated NLR.
PMID- 28418873
TI - Combined inhibition of GLI and FLT3 signaling leads to effective anti-leukemic
effects in human acute myeloid leukemia.
AB - Activation of the Hedgehog pathway has been implicated in the pathogenesis of
several tumor types including myeloid leukemia. Previously we demonstrated that
overexpression of Hedgehog downstream mediators GLI1/2 confers an adverse
prognosis to patients with acute myeloid leukemia (AML) and is correlated with a
FLT3 mutated status. To analyze a possible non-canonical activation of the
Hedgehog pathway via FLT3 and PI3K, we performed blocking experiments utilizing
inhibitors for FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61) in FLT3
mutated and FLT3 wildtype AML cell lines and primary blasts. Combination of all
three compounds had stronger anti-leukemic effects in FLT3-mutated compared to
FLT3 wildtype AML cells in vitro. Interestingly, the colony growth of normal
CD34+ cells from healthy donors was not impeded by the triple inhibitor
combination possibly opening a therapeutic window for the clinical use of
inhibitor combinations. Besides, combined treatment with sunitinib, PF-04691502
and GANT61 significantly prolonged the survival of mice transplanted with FLT3
mutated MV4-11 cells compared to the single agent treatments. Furthermore, the
inhibition of FLT3 and PI3K resulted in reduced GLI protein expression and
promotor activity in FLT3-mutated but not in FLT3 wildtype AML cell lines in
western blotting and GLI1/2 promoter assays supporting our hypothesis of non
canonical GLI activation via FLT3.In summary, FLT3-mutated in contrast to FLT3
wildtype cells or normal human hematopoietic progenitor cells are exquisitely
sensitive to combined inhibition by FLT3, PI3K and GLI1/2 overcoming some of the
limitations of current FLT3 directed therapy in AML. The development of GLI1/2
inhibitors is highly desirable.
PMID- 28418874
TI - Is there a prognostic value of tumor location among Chinese patients with
colorectal cancer?
AB - Differences in epidemiology, pathological features, and molecular pathogeneses
have been observed according to primary tumor location in colorectal cancer
(CRC). However, predicting CRC survival by tumor location remains controversial.
Therefore, we compared the pathological characteristics, molecular features, and
prognoses of right-side colon cancer (RCC), left-side colon cancer (LCC), and
rectal cancer (RECC) among Chinese patients with CRC. We evaluated 4,426 patients
with stage I-III CRC between January 2008 and July 2014from Fudan University
Shanghai Cancer Center. All patients were grouped by the locations of tumors
(RCC, LCC, and RECC). Patients with RCC were more likely to be women and older,
have poorly differentiated tumors, microsatellite repair deficiency (dMMR),
negative p53 expression, and the mucinous subtype. Unadjusted Kaplan-Meier
survival curves revealed survival in RCC than in LCC and RECC. However, there
were no significant differences in OS and DFS between LCC and RECC. The same
results were observed for each disease stage. Unadjusted models revealed an
increased risk of mortality, recurrence, or metastasis for RCC (OS: HR, 1.68,
P=0.0002 and DFS: HR, 1.24, P=0.032), compared to LCC (all stages), and a similar
result was observed for stage III patients (OS: HR, 1.79, P<0.0001 and DFS: HR,
1.33, P=0.021). However, adjusted Cox proportional hazard regression models
revealed no significant differences in survival between the three tumor
locations. Tumor location was not an independent prognostic factor among Chinese
patients with stage I-III CRC. But RCCs had a worse prognosis in the dMMR
subgroup. The related mechanism remains to be investigated.
PMID- 28418876
TI - PPARGC1A rs3736265 G>A polymorphism is associated with decreased risk of type 2
diabetes mellitus and fasting plasma glucose level.
AB - It has been reported that peroxisome proliferator-activated receptor gamma
(PPARG) and peroxisome proliferator-activated receptor gamma co-activator 1
(PPARGC1) family (e.g. PPARGC1A and PPARGC1B) are key agents in the development
and pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we
designed a case-control study and selected PPARG rs1801282 C>G, PPARG rs3856806
C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A,
PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms to assess the
relationship between these polymorphisms and T2DM using the SNPscan method. A
total of 502 T2DM patients and 784 non-diabetic controls were enrolled. We found
that PPARGC1A rs3736265 G>A polymorphism was correlated with a borderline
decreased susceptibility of T2DM. In a subgroup analysis by age, sex, alcohol
use, smoking status and body mass index, a significantly decreased risk of T2DM
in <65 years and female groups was found. Haplotype comparison analysis indicated
that CTTCGGG and CTCTGGG haplotypes with the order of PPARG rs1801282 C>G, PPARG
rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265
G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms in gene
position significantly increased the risk of T2DM. However, CCCCACA haplotype
conferred a decreased risk to T2DM. We also found that PPARGC1A rs3736265 A
allele decreased the level of fasting plasma glucose (FPG), while increased the
level of Triglyceride. In conclusion, Our findings suggest that variants of
PPARGC1A rs3736265 G>A polymorphism decrease the level of FPG, improving the
expectation of study in individual's prevention strategies to T2DM.
PMID- 28418877
TI - Transforming growth factor-beta1 promotes breast cancer metastasis by
downregulating miR-196a-3p expression.
AB - Transforming growth factor-beta1 is considered a key contributor to the
progression of breast cancer. MicroRNAs are important factors in the development
and progression of many malignancies. In the present study, upon studies of
breast cancer cell lines and tissues, we showed that microRNA -196a-3p is
decreased by transforming growth factor-beta1 in breast cancer cells and
associated with breast cancer progression. We identified neuropilin-2 as a target
gene of microRNA -196a-3p and showed that it is regulated by transforming growth
factor-beta1. Moreover, transforming growth factor-beta1-mediated inhibition of
microRNA -196a-3p and activation of neuropilin-2were required for transforming
growth factor-beta1-induced migration and invasion of breast cancer cells. In
addition, neuropilin-2 expression was suppressed in breast tumors, particularly
in triple-negative breast cancers. Collectively, our findings strongly indicate
that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and
patient survival and a potential therapeutic target in metastatic breast cancer.
PMID- 28418879
TI - Transcriptome profiling reveals miR-9-3p as a novel tumor suppressor in gastric
cancer.
AB - It has been well established that microRNAs (miRNAs) play important roles in
biological processes. To comprehensively measure the altered miRNA expression, we
presented the miRNA expression profile of gastric cancer using microarray. We
identified 33 miRNAs that were significantly differentially regulated in gastric
specimens compared to adjacent normal tissues, among which miR-9-3p expression
are significantly down-regulated in gastric cancers. Next, a cohort of 100
gastric cancer tissues and matched normal tissues were enrolled. Kaplan-Meier and
multivariate Cox survival analyses were applied to evaluate the prognostic value
of miR-9-3p expression, and the result showed that patients with lower miR-9-3p
expression level have significantly poorer overall survival. The expression level
of miR-9-3p has been proved to be an independent prognostic factor for 5-year
overall survival. Furthermore, the result indicated that over-expression of miR-9
3p can inhibit gastric cancer cell invasion. Taken together, our results
suggested that miR-9-3p plays important role in tumor invasion, and these
findings implicated the potential effects of miR-9-3p on prognosis of gastric
cancer.
PMID- 28418878
TI - The TERT rs2736100 polymorphism increases cancer risk: A meta-analysis.
AB - Abnormal telomerase activity is implicated in cancer initiation and development.
The rs2736100 T > G polymorphism in the telomerase reverse transcriptase (TERT)
gene, which encodes the telomerase catalytic subunit, has been associated with
increased cancer risk. We conducted a meta-analysis to more precisely assess this
association. After a comprehensive literature search of the PubMed and EMBASE
databases up to November 1, 2016, 61 articles with 72 studies comprising 108,248
cases and 161,472 controls were included in our meta-analysis. Studies were
conducted on various cancer types. The TERT rs2736100 polymorphism was associated
with increased overall cancer risk in five genetic models [homozygous model (GG
vs. TT): odds ratio (OR) = 1.39, 95% confidence interval (95% CI) = 1.26-1.54, P
< 0.001; heterozygous model (TG vs. TT): OR = 1.16, 95% CI = 1.11-1.23, P <
0.001; dominant model (TG + GG vs. TT): OR = 1.23, 95% CI = 1.15-1.31, P < 0.001;
recessive model (GG vs. TG + TT): OR = 1.25, 95% CI = 1.16-1.35, P < 0.001; and
allele contrast model (G vs. T): OR = 1.17, 95% CI = 1.12-1.23, P < 0.001]. A
stratified analysis based on cancer type associated the polymorphism with
elevated risk of thyroid cancer, bladder cancer, lung cancer, glioma,
myeloproliferative neoplasms, and acute myeloid leukemia. Our results confirm
that the TERT rs2736100 polymorphism confers increased overall cancer risk.
PMID- 28418880
TI - Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance
in chronic myeloid leukemia cells.
AB - Resistance to the breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase
inhibitor (TKI) imatinib poses a major problem when treating chronic myeloid
leukemia (CML). Imatinib resistance often results from a secondary mutation in
BCR-ABL1. However, in the absence of a mutation in BCR-ABL1, the basis of BCR
ABL1-independent resistance must be elucidated. To gain insight into the
mechanisms of BCR-ABL1-independent imatinib resistance, we performed an array
based comparative genomic hybridization. We identified various resistance-related
genes, and focused on MET. Treatment with a MET inhibitor resensitized K562/IR
cells to BCR-ABL1 TKIs. Combined treatment of K562/IR cells with imatinib and a
MET inhibitor suppressed extracellular signal-regulated kinase 1/2 (ERK1/2) and c
Jun N-terminal kinase (JNK) activation, but did not affect AKT activation. Our
findings implicate the MET/ERK and MET/JNK pathways in conferring resistance to
imatinib, providing new insights into the mechanisms of BCR-ABL1 TKI resistance
in CML.
PMID- 28418881
TI - Aspirin as a potential modality for the chemoprevention of breast cancer: A dose
response meta-analysis of cohort studies from 857,831 participants.
AB - BACKGROUND: Previous meta-analyses on the relationship between aspirin use and
breast cancer risk have drawn inconsistent results. In addition, the threshold
effect of different doses, frequencies and durations of aspirin use in preventing
breast cancer have yet to be established. RESULTS: The search yielded 13
prospective cohort studies (N=857,831 participants) that reported an average of
7.6 cases/1,000 person-years of breast cancer during a follow-up period of from
4.4 to 14 years. With a random effects model, a borderline significant inverse
association was observed between overall aspirin use and breast cancer risk, with
a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model
was a better fit for the dose-response relationship, which displayed a potential
relationship between the frequency of aspirin use and breast cancer risk (RR =
0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It
was also a better fit for the duration of aspirin use and breast cancer risk (RR
= 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use). METHODS: We
searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for
relevant prospective cohort studies of aspirin use and breast cancer risk. Meta
analysis of relative risks (RR) estimates associated with aspirin intake were
presented by fixed or random effects models. The dose-response meta-analysis was
performed by linear trend regression and restricted cubic spline regression.
CONCLUSION: Our study confirmed a dose-response relationship between aspirin use
and breast cancer risk. For clinical prevention, long term (>5 years) consistent
use (2-7 times/week) of aspirin appears to be more effective in achieving a
protective effect against breast cancer.
PMID- 28418882
TI - Oncogenic histone methyltransferase EZH2: A novel prognostic marker with
therapeutic potential in endometrial cancer.
AB - The histone methyltransferase EZH2, a key epigenetic modifier, is known to be
associated with human tumorigenesis. However, the physiological importance of
EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in
the present study, we investigated the expression and function of EZH2 in
endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial
cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was
significantly overexpressed in cancer cells and tissues compared to that in
corresponding normal control cells and tissues. Kaplan-Meier survival analysis
using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated
that EZH2 overexpression is associated with endometrial cancer prognosis. In
addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression
and apoptosis induction of endometrial cancer cells, accompanied by attenuation
of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a
specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased
the number of cancer cell colonies. Furthermore, GSK126 showed additive effects
with doxorubicin or cisplatin, which are conventional drugs for treatment of
endometrial cancer. Further studies should explore the therapeutic potential of
inhibiting EZH2 in patients with endometrial cancer.
PMID- 28418883
TI - Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and
proliferation.
AB - Targeting cancer stem cells during initial treatment is important to reduce
incidence of recurrent disease. Bmi1 has been associated with cancer stem cell
self-renewal and aggressive disease. The purpose of this study was to determine
the effects of downregulation of Bmi1 in breast cancer stem cells in order to
target and eliminate the stem cell population in the tumor mass. Bmi1 was
downregulated using two approaches in the mouse breast cancer stem cell line FMMC
419II-a small molecule inhibitor (PTC 209) and stable transfection with a Bmi1
shRNA plasmid. The functional effect of Bmi1 downregulation was tested in vitro
and in vivo. Each approach led to decreased Bmi1 expression that correlated with
an inhibition of cancer stem cell properties in vitro including cell cycle arrest
and reduced mammosphere forming potential, and a decrease in tumor mass in vivo
after either intra-tumoral or systemic nanoparticle-targeted delivery of anti
Bmi1. These results show that inhibiting Bmi1 expression in breast cancer stem
cells could be important for the complete elimination of tumor and potentially
preventing disease relapse.
PMID- 28418884
TI - The association between miR-423 rs6505162 polymorphism and cancer susceptibility:
a systematic review and meta-analysis.
AB - The association between miR-423 polymorphism (C > A) and the risk of different
cancers are still controversial. We performed a meta-analysis to clarify its
association with multiple cancer risks. PubMed and Embase (as of 10th September,
2016) were searched. A total of 17 studies from 16 articles, consisting of 8,582
cases and 10,291 controls, were finally qualified and enrolled in this meta
analysis. The pooled results showed that the miR-423 AA genotype was associated
with decreased cancer risk under the recessive model (odds ratio [OR] = 0.87, 95%
confidence interval [CI]: 0.78~0.98, P = 0.020). However, this association became
non-significant after excluding the study with the smallest odds ratio. Subgroup
analyses revealed a significant decrease in risk of lung cancer (dominant model:
OR = 0.73, 95 % CI: 0.60~0.89, P = 0.002; recessive model: OR = 0.59, 95 % CI:
0.37~0.95, P = 0.031). Our study indicates that miR-423 rs6505162 might be
associated with a reduced risk of cancers, however, this finding need to be
evaluated further in larger samples, especially subgroup analyses. In addition,
cancer-specific functional studies are especially needed to reveal the underlying
mechanisms between miR-423 and the etiology of cancer.
PMID- 28418885
TI - Development of [11C]vemurafenib employing a carbon-11 carbonylative Stille
coupling and preliminary evaluation in mice bearing melanoma tumor xenografts.
AB - Over the last decade kinase inhibitors have witnessed tremendous growth as anti
cancer drugs. Unfortunately, despite their promising clinical successes, a large
portion of patients does not benefit from these targeted therapeutics.
Vemurafenib is a serine/threonine kinase inhibitor approved for the treatment of
melanomas specifically expressing the BRAFV600E mutation. The aim of this study
was to develop vemurafenib as PET tracer to determine its potential for
identification of tumors sensitive to vemurafenib treatment. Therefore,
vemurafenib was labeled with carbon-11 and analyzed for its tumor targeting
potential in melanoma xenografts Colo829 (BRAFV600E) and MeWo (BRAFwt) using
autoradiography on tissue sections, in vitro tumor cell uptake studies and
biodistribution studies in xenografted athymic nu/nu mice. [11C]vemurafenib was
synthesized in 21 +/- 4% yield (decay corrected, calculated from [11C]CO) in >
99% radiochemical purity and a specific activity of 55 +/- 18 GBq/MUmol. Similar
binding of [11C]vemurafenib was shown during autoradiography and cellular uptake
studies in both cell lines. Plasma metabolite analysis demonstrated > 95% intact
[11C]vemurafenib in vivo at 45 minutes after injection, indicating excellent
stability. Biodistribution studies confirmed the in vitro results, showing
similar tumor-to-background ratios in both xenografts models. These preliminary
results suggest that identification of BRAFV600E mutations in vivo using PET with
[11C]vemurafenib will be challenging.
PMID- 28418886
TI - Histone hypoacetylation contributes to CXCL12 downregulation in colon cancer:
impact on tumor growth and cell migration.
AB - CXCL12 has been shown to be involved in colon cancer metastasis, but its
expression level and molecular mechanisms regulating its expression remain
controversial. We thus evaluated CXCL12 expression in a large cohort of colon
adenomas and carcinomas, investigated for an epigenetic mechanism controlling its
expression and evaluated the impact of CXCL12 levels on cell migration and tumor
growth. CXCL12 expression was measured in human colon adenomas and carcinomas
with transcriptome array and RT-qPCR. The promoter methylation was analyzed with
whole-genome DNA methylation chips and protein expression by
immunohistochemistry. We confirm a reduced expression of CXCL12 in 75% of MSS
carcinomas and show that the decrease is an early event as already present in
adenomas. The methylome analysis shows that the CXCL12 promoter is methylated in
only 30% of microsatellite-stable tumors. In vitro, treatments with HDAC
inhibitors, butyrate and valproate restored CXCL12 expression in three colon cell
lines, increased acetylation of histone H3 within the CXCL12 promoter and
inhibited cell migration. In vivo, valproate diminished (65%) the number of
intestinal tumors in APC mutant mice, slowed down xenograft tumor growth
concomitant to restored CXCL12 expression. Finally we identified loss of PCAF
expression in tumor samples and showed that forced expression of PCAF in colon
cancer cell lines restored CXCL12 expression. Thus, reduced PCAF expression may
participate to CXCL12 promoter hypoacetylation and its subsequent loss of
expression. Our study is of potential clinical interest because agents that
promote or maintain histone acetylation through HDAC inhibition and/or HAT
stimulation, may help to lower colon adenoma/carcinoma incidence, especially in
high-risk families, or could be included in therapeutic protocols to treat
advanced colon cancer.
PMID- 28418887
TI - Metastasis-associated protein 3 in colorectal cancer determines tumor recurrence
and prognosis.
AB - Metastasis-associated protein family (MTA) promotes tumor cell invasion and
metastasis of human malignancies. However, the novel component of MTA family,
MTA3 was found to play conflicting roles in human malignancies. While the
expression pattern and potential function of MTA3 in colorectal cancer has not
been addressed yet. In the present study, we investigated the protein expression
of MTA3 by immunohistochemistry assay, analyzed its association with tumor
progression, recurrence and prognosis in239 cases of patients. Results showed
that MTA3 expression in colorectal cancer was significantly decreased in
colorectal cancer compared with normal specimens. Its expression was found to be
correlated with tumor differentiation, metastases and TNM stage. Kaplan-Meier
analysis proved that MTA3 was associated with both disease-free survival and
overall survival of patients with colorectal cancer that patients with negative
MTA3 expression tend to have unfavorable outcome. Moreover, cox's proportional
hazards analysis showed that negative MTA3 expression was an independent
prognostic marker of poor outcome. These results provided the first evidence that
MTA3 level was decreased in colorectal cancer and significantly correlated with
tumor cell invasion and metastasis. It also demonstrated that MTA3 might serve as
a potential marker of tumor recurrence and prognosis of colorectal cancer.
PMID- 28418888
TI - Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous
cell carcinoma and its potential as a target for anti-metastasis therapy.
AB - Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma
(ESCC). The aim of the study is to identify key signaling pathways that control
metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were
established through three rounds of selection of cancer cells invading through
matrigel-coated chambers. Gene expression profile of one of the I3 sublines was
compared with that of its parental cell line using cDNA microarray analysis. Gene
ontology and pathway analyses of the differentially expressed genes (both
upregulated and downregulated) indicated that genes associated with cellular
movement and the AKT pathway were associated with increased cancer cell
invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p
AKT), N-cadherin and decreased E-cadherin expression in the I3 cells.
Immunohistochemistry was used to evaluate the clinical significance of p-AKT
expression in ESCC, and the results showed higher p-AKT nuclear expression in
lymph node metastases when compared with primary carcinoma. Inactivation of the
PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted
in reversed cadherin switching and inhibited cancer cell motility. Inhibition of
the pathway by treatment with wortmannin markedly suppressed experimental
metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT
signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic
target in treatment of metastatic ESCC.
PMID- 28418890
TI - The serum 25-hydroxyvitamin D levels and hip fracture risk: a meta-analysis of
prospective cohort studies.
AB - Hip fracture has increasingly become a social and economic burden. The
relationship between serum 25-hydroxyvitamin D levels and the risk of hip
fracture reported by previous studies remains controversial. We searched Pubmed
and Embase to identify studies reporting the relationship between serum 25
hydroxyvitamin D levels and risk of hip fracture. Fifteen prospective cohort
studies with a total of 51239 participants and 3386 hip fracture cases were
included. By pooling the Relative Risk of the lowest vs. the highest categories
indicated that lower levels of serum 25-hydroxyvitamin D were more likely to be a
risk factor for hip fracture with adjusted Relative Risk (95%Confidence Interval)
of 1.58 (1.41, 1.77). Subgroup meta-analysis examining the stability of the
primary results achieved the same results. A dose-response meta-analysis showed
that the risk of hip fracture was a descending curve below the line of RR=1. The
descending trend was obvious when serum 25-hydroxyvitamin D levels were less than
60 nmol/L and was flat when serum 25-hydroxyvitamin D levels were more than 60
nmol/L. We found that individuals with low levels of serum 25-hydroxyvitamin D
have an increased risk of hip fracture, and this effect was evident when the
serum 25-hydroxyvitamin D levels were less than 60 nmol/L.
PMID- 28418894
TI - Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell
renal cell carcinoma.
AB - Clear cell Renal Cell Carcinoma (ccRCC) causes over 13,000 deaths each year, and
about 20,000 new cases/year in Europe. In most cases, the causes are unknown and,
most importantly, there are no reliable biomarkers for the diagnosis and
prognosis of this disease. The search for sensitive biomarkers for early
diagnosis and prognosis of clear cell Renal Cell Carcinoma (ccRCC) is currently a
fast growing field. We carried out proteomics analysis of 93 urinary samples of
healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and
chronic kidney disease (CKD), that was able to successfully distinguish each
group.The most significant candidate biomarker was identified by mass
spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell
signaling, already described in several cancer types as a metastasis suppressor.
By combining ELISA, immunoblotting and tissue microarray, we demonstrated that,
in ccRCC, urinary excretion of RKIP and its phosphorylated form (p-RKIP)
reflected the tissue expression of these putative biomarkers. Baseline urinary
RKIP, evaluated in an independent cohort of 56 ccRCC patients and 28 HS,
successfully distinguished both groups and, most importantly, a cut-off value of
10 ng/mg/g Pr/uCr enabled a highly accurate prediction of Cancer-specific
survival and Progression-free survival. Furthermore, p-RKIP was totally
undetectable in both tissue and urine samples of ccRCC, showing a great potential
for diagnostics purposes.Our data indicate that urinary RKIP encompasses both the
unphosphorylated and the phosphorylated form and that their combined evaluation
can help in the diagnosis and prognosis of ccRCC.
PMID- 28418892
TI - Roles of long noncoding RNAs in colorectal cancer metastasis.
AB - Colorectal cancer (CRC) is the 3rd most common malignancies worldwide. Metastasis
is responsible for more than 90% CRC patients' death. Long noncoding RNAs
(lncRNAs) are an important class of transcribed RNA molecules greater than 200
nucleotides in length. With the development of whole genome sequencing
technologies, they have been gained more attention. Accumulating evidences
suggest that abnormal expression of lncRNAs in diverse diseases are involved in
various biological functions such as proliferation, apoptosis, metastasis and
differentiation by acting as epigenetic, splicing, transcriptional or post
transcriptional regulators. Aberrant expression of lncRNAs has also been found in
CRC. Besides, recent studies have indicated that lncRNAs play important roles in
tumourigenesis and cancer metastasis. They participate in the process of
metastasis by activing or inhibiting the metastatic pathways. However, their
functions on the development of cancer metastasis are poorly understood. In this
review, we highlight the findings of roles for lncRNAs in CRC metastasis and
review the metastatic pathways of lncRNAs leading to cancer metastasis in CRC,
including escape of apoptosis, epithelial-mesenchymal transition (EMT),
angiogenesis and invasion, migration and proliferation. Furthermore, we also
discuss the potential clinical application of lncRNAs in CRC as diagnostic
markers and therapeutic targets.
PMID- 28418896
TI - NFkB is essential for activin-induced colorectal cancer migration via
upregulation of PI3K-MDM2 pathway.
AB - Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic
disease. Activin and TGFB (TGFbeta) signaling are growth suppressive pathways
that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We
have recently shown that activin downregulates p21 via ubiquitination and
degradation associated with enhanced cellular migration independent of SMADs. To
investigate the mechanism of metastatic activin signaling, we examined activated
NFkB signaling and activin ligand expression in CRC patient samples and found a
strong correlation. We hypothesize that activation of the E3 ubiquitin ligase
MDM2 by NFkB leads to p21 degradation in response to activin treatment. To
dissect the link between activin and pro-carcinogenic NFkB signaling and
downstream targets, we found that activin but not TGFB induced activation of NFkB
leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of
wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO
binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2.
In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce
MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism.
This provides new mechanistic knowledge linking activin and NFkB signaling in
advanced colon cancer which is applicable to targeted therapeutic interventions.
PMID- 28418897
TI - Treatment for retropharyngeal metastatic undifferentiated squamous cell carcinoma
from an unknown primary site: results of a prospective study with irradiation to
nasopharyngeal mucosa plus bilateral neck.
AB - : Background and Objetive: To evaluate treatment outcomes for patients with
retropharyngeal metastatic undifferentiated squamous cell carcinoma (SCC) from an
unknown primary site. METHODS: From January 2005 to January 2015, patients who
presented with enlarged retropharyngeal nodes underwent transoral sonography
guided fine-needle aspiration to confirm histology. Those with metastatic
undifferentiated SCC with unknown primary tumors were treated with radical
radiotherapy to nasopharyngeal mucosa plus bilateral neck. Chemotherapy was
administered for patients staged N2-3. Endpoints included metastatic nodes
control, the appearance of primary tumor, overall survival and treatment-related
toxicities. RESULTS: A total of 49 patients were recruited into this study.
Retropharyngeal and cervical nodal disease was controlled in 96% of all patients.
The incidence of occult primary cancer appearance was 8%. No primary cancer other
than of the nasopharynx was detected during the course of follow-up. Ten patients
developed distant metastases. The 5-year overall survival, progression-free
survival, regional relapse free survival, distant metastasis free survival were
79.6%, 61.1%, 83.4%, 73.8%, respectively. Common late adverse effects included
xerostomia (57%) and hearing impairment (35%). CONCLUSION: Radical radiotherapy
to both the nasopharynx and bilateral neck can achieve excellent outcome with
mild toxicities for patients with retropharyngeal metastatic undifferentiated
squamous cell carcinoma from an unknown primary site.
PMID- 28418898
TI - PLCE1 polymorphisms and expression combined with serum AFP level predicts
survival of HBV-related hepatocellular carcinoma patients after hepatectomy.
AB - Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in
the development and progression of several types of cancer. The present study
investigated the prognostic significance of PLCE1 gene polymorphisms and
expression combined with serum alpha-fetoprotein (AFP) level in hepatitis B virus
(HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms
were genotyped by sequencing DNA isolated from surgically resected tumor samples
of 421 HBV-related HCC patients, and expression profiles were generated based on
the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes
(Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20
ng/ml showed a significant association with overall survival(OS) of HBV-related
HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP
level >= 20 ng/ml had an increased risk of death as compared to those with the AC
haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively).
Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased
risk of death, although with a non-significant P value (adjusted P=0.092). Joint
effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300
ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our
results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and
expression combined with serum AFP level may predict postoperative outcome of HBV
related HCC patients.
PMID- 28418899
TI - An exploration of the role of a fish-oriented diet in cognitive decline: a
systematic review of the literature.
AB - Epidemiological studies have presented inconsistent evidence of the correlation
between a fish-oriented dietary intake (FDI) and the risk of cognitive decline.
To address these controversies, we performed this systematic review of
prospective studies published in December 2016 and earlier using PubMed, Embase,
and Web of Science. Two independent researchers conducted the eligibility
assessment and data extraction; all discrepancies were solved by discussion with
a third researcher. The pooled relative risks (RRs) focused on the incidence of
events were estimated with 95% confidence intervals (CIs). Overall, nine studies
containing 28,754 subjects were analyzed. When the highest and lowest categories
of fish consumption were compared, the summary RR for dementia of Alzheimer type
(DAT) was 0.80 (95%CI = 0.65-0.97); i.e., people with a higher intake of fish had
a 20% (95%CI = 3-35%) decreased risk of DAT. Additionally, the dose-response
synthesized data indicated that a 100-g/week increase in fish intake reduced the
risk of DAT by an additional 12% (RR = 0.88, 95%CI = 0.79-0.99). Non-significant
results were observed for the risk of dementia of all causes (DAC) and mild
cognitive impairment (MCI). Limited evidence involving heterogeneity was found
within subgroups or across studies. In conclusion, this review confirmed that a
higher intake of fish could be correlated with a reduced risk of DAT. Further
research, especially prospective studies that specifically quantify FDI, will
help find a more accurate assessment of the different levels of dietary intake.
PMID- 28418900
TI - Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a
strategy to overcome TP53 mutated/deleted clones.
AB - Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either
indolent or aggressive clinical course. Current treatment regiments have
significantly improved the overall outcomes even if higher risk subgroups - those
harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p)
remain highly challenging. In the present work, we identified USP7, a known de
ubiquitinase with multiple roles in cellular homeostasis, as a potential
therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL
cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p
and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2),
an upstream interactor known to be deregulated in CLL; iii) effectively targeted
by the USP7 inhibitor P5091. Treatment of primary CLL samples and cell lines with
P5091 induces cell growth arrest and apoptosis, through the restoration of PTEN
nuclear pool, both in TP53-wild type and -null environment. Importantly, PTEN
acts as the main tumor suppressive mediator along the USP7-PTEN axis in a p53
dispensable manner. In conclusion, we propose USP7 as a new druggable target in
CLL.
PMID- 28418901
TI - Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal
carcinoma patients: a network meta-analysis.
AB - OBJECT: A Bayesian network meta-analysis (NMA) was conducted to estimate the
overall survival (OS) and complete response (CR) performance in nasopharyngeal
carcinoma (NPC) patients who have been given the treatment of radiotherapy,
concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant
chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A),
concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant
chemotherapy with adjuvant chemotherapy (N+A). METHODS: Literature search was
conducted in electronic databases. Hazard ratios (HRs) accompanied their 95%
confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to
measure the relative survival benefit between two comparators. Meanwhile odd
ratios (ORs) with their 95% CIs or CrIs were given to present CR data from
individual studies. RESULTS: Totally 52 qualified studies with 10,081 patients
were included in this NMA. In conventional meta-analysis (MA), patients with N+C
exhibited an average increase of 9% in the 3-year OS in relation to those with
C+A. As for the NMA results, five therapies were associated with a significantly
reduced HR when compared with the control group when concerning 5-year OS. C, C+A
and N+A also presented a decreased HR compared with A. There was continuity among
1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three
chemoradiotherapy appeared to be divided into the most compete group which is
located in the upper right corner of the cluster plot. CONCLUSION: In view of
survival rate and complete response, the NMA results revealed that C, C+A and C+N
showed excellent efficacy. As a result, these 3 therapies were supposed to be
considered as the first-line treatment according to this NMA.
PMID- 28418902
TI - IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance
to erlotinib in HCC827 NSCLC cells.
AB - EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2
years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance
mechanisms have been identified including secondary EGFR-mutations, MET
amplification, and epithelial-mesenchymal transition (EMT). Previous studies have
indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired
resistance to EGFR-directed drugs as well as in EMT. In the present study, we
have investigated the involvement of IGF1R in acquired high-dose erlotinib
resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827. We observed
that IGF1R was upregulated in the immediate response to erlotinib and
hyperactivated in erlotinib resistant HCC827 cells. Resistant cells additionally
acquired features of EMT, whereas MET-amplification and secondary EGFR-mutations
were absent. Using CRISPR/Cas9, we generated a HCC827(IGFR1-/-) cell line and
subsequently investigated resistance development in response to high-dose
erlotinib. Interestingly, HCC827(IGFR1-/-) cells were now observed to
specifically amplify the MET gene. Additionally, we observed a reduced level of
mesenchymal markers in HCC827(IGFR1-/-) indicating an intrinsic enhanced
epithelial signature compared to HCC827 cells. In conclusion, our data show that
IGF1R have an important role in defining selected resistance mechanisms in
response to high doses of erlotinib.
PMID- 28418903
TI - Kinomic profiling identifies focal adhesion kinase 1 as a therapeutic target in
advanced clear cell renal cell carcinoma.
AB - The introduction of targeted therapies has caused a paradigm shift in the
treatment of metastatic clear cell (cc)-renal cell carcinoma (RCC). We
hypothesized that determining differential kinase activity between primary and
metastatic tumor sites may identify critical drivers of progression and relevant
therapeutic targets in metastatic disease. Kinomic profiling was performed on
primary tumor and metastatic tumor deposits utilizing a peptide substrate
microarray to detect relative tyrosine phosphorylation activity. Pharmacologic
and genetic loss of function experiments were used to assess the biologic
significance of the top scoring kinase on in vitro and in vivo tumor phenotypes.
Kinomics identified 7 peptides with increased tyrosine phosphorylation in
metastases that were significantly altered (p<0.005). Based on these peptides,
bioinformatics analyses identified several candidate kinases activated in
metastases compared to primary tumors. The highest ranked upstream kinase was
Focal Adhesion Kinase 1 (FAK1). RCC lines demonstrate evidence of elevated FAK1
activation relative to non-transformed renal epithelial cells. Pharmacologic
inhibition of FAK1 with GSK2256098 suppresses in vitro tumor phenotypes. In turn,
FAK1 knockdown in RCC cells suppresses both in vitro phenotypes and in vivo tumor
growth. Collectively, these data demonstrate functional activation of FAK1 in
metastases and provide preclinical rationale for targeting this kinase in the
setting of advanced ccRCC.
PMID- 28418904
TI - A consensus-hemagglutinin-based vaccine delivered by an attenuated Salmonella
mutant protects chickens against heterologous H7N1 influenza virus.
AB - H7N3 and H7N7 are highly pathogenic avian influenza (HPAI) viruses and have posed
a great threat not only for the poultry industry but for the human health as
well. H7N9, a low pathogenic avian influenza (LPAI) virus, is also highly
pathogenic to humans, and there is a great concern that these H7 subtypes would
acquire the ability to spread efficiently between humans, thereby becoming a
pandemic threat. A vaccine candidate covering all the three subtypes must,
therefore, be an integral part of any pandemic preparedness plan. To address this
need, we constructed a consensus hemagglutinin (HA) sequence of H7N3, H7N7, and
H7N9 based on the data available in the NCBI in early 2012-2015. This artificial
sequence was then optimized for protein expression before being transformed into
an attenuated auxotrophic mutant of Salmonella Typhimurium, JOL1863 strain.
Immunizing chickens with JOL1863, delivered intramuscularly, nasally or orally,
elicited efficient humoral and cell mediated immune responses, independently of
the route of vaccination. Our results also showed that JOL1863 deliver efficient
maturation signals to chicken monocyte derived dendritic cells (MoDCs) which were
characterized by upregulation of costimulatory molecules and higher cytokine
induction. Moreover, immunization with JOL1863 in chickens conferred a
significant protection against the heterologous LPAI H7N1 virus challenge as
indicated by reduced viral sheddings in the cloacal swabs. We conclude that this
vaccine, based on a consensus HA, could induce broader spectrum of protection
against divergent H7 influenza viruses and thus warrants further study.
PMID- 28418905
TI - Expression pattern of genome-scale long noncoding RNA following acute myocardial
infarction in Chinese Uyghur patients.
AB - In this study, we examined the long noncoding RNA (lncRNA) expression pattern in
Uyghur patients (a minority of China) with acute myocardial infarction (AMI) on a
genome-wide scale. Total RNAs were extracted from the peripheral blood of 55
Uyghur AMI patients and 55 healthy volunteers. The expression levels of genome
wide scale lncRNAs and mRNAs were determined by microarray in 10 samples (5 AMI
and 5 controls). qRT-PCR was used to validate lncRNA expression levels in 100
samples (50 AMI and 50 controls). Data analyses were performed using R and
Bioconductor. A total of 3624 up- and 1637 down-regulated lncRNAs were identified
to be significantly and differentially expressed between these two groups. The
annotation result of their co-expressed mRNAs showed that the most significantly
related category of GO analysis was regulation of biological processes, and the
most significantly related pathway was apoptosis and its corresponding p53. The
microarray identified ENST00000416860.2, ENST00000421157.1 and TCONS_00025701
lncRNAs were confirmed by qRT-PCR. Our study indicated that clusters of lncRNAs
were significantly and differentially expressed in the peripheral blood of AMI
patients when compared with healthy controls within the Uyghur population. These
newly identified lncRNAs may have a potential role in the development of AMI.
PMID- 28418906
TI - The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical
outcomes of breast cancer patients in northern China.
AB - BACKGROUND: Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the
differentiation of clinical outcomes among breast cancer women. This study aimed
to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4
genes with clinicopathological features, protein expression and prognosis of
breast cancer in the northern Chinese population. RESULTS: Firstly, SNP
rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated
with age and menstruation status. And SNP rs11636419 and rs17861162 were
associated with the P53 status. Secondly, SNP rs2470890 was correlated with
CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P
= 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan-Meier 5 year
survival curves showed that patients carrying genotypes CT or TT had a worse OS
compared with the genotype CC carriers under both codominant and dominant model
(P < 0.001, P < 0.001, respectively). MATERIALS AND METHODS: Four single
nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer
patients using the SNaPshot method. The associations of four polymorphisms with
protein expression and clinicopathological characteristics were evaluated by
Pearson's chi-square test. The Cox hazard regression analysis and Kaplan-Meier
survival analysis were performed to evaluate the relationship between the SNPs
and overall survival (OS) of breast cancer. CONCLUSIONS: CYP1A2 rs2470890 was
significantly associated with the prognosis of patients with breast cancer and
could serve as an independent impact factor of prognosis of breast carcinoma.
PMID- 28418907
TI - BH3-mimetics and BET-inhibitors elicit enhanced lethality in malignant glioma.
AB - Drug combination therapies remain pivotal for the treatment of heterogeneous
malignancies, such as glioblastomas. Here, we show a novel lethal interaction
between Bcl-xL and c-myc inhibition accomplished by bromodomain protein
inhibitors. Established, patient-derived xenograft and stem cell-like glioma
cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015,
along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation
of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and
mechanistic studies. In vivo experiments were performed in a glioblastoma
xenograft model. Single treatments with JQ1 and OTX015 had only moderate effects
on the reduction of cellular viability. However, the combination treatment of BH3
mimetics along with JQ1 or OTX015 resulted in a highly synergistic reduction of
cellular viability in a broad range of different model systems of malignant
glioma. Similarly, knockdown of c-myc sensitized glioma cells for ABT263 mediated
cell death. The enhanced loss of cellular viability in the combination treatment
was mediated by activation of apoptosis with dissipation of mitochondrial
membrane potential and caspase cleavage. The combination treatment led to a
modulation of anti- and pro-apoptotic Bcl-2 family members with an increase in
pro-apoptotic Noxa mediated by ATF4. Small interfering RNA mediated knockdown of
Bak and Noxa protected glioma cells from ABT263/JQ1 mediated apoptosis. Finally,
the combination treatment of ABT263 and OTX015 resulted in a regression of tumors
and a significantly smaller tumor size as compared to single or vehicle treated
tumors. Thus, these results warrant clinical testing for the drug combination of
BH3-mimetics along with bromodain protein inhibitors.
PMID- 28418909
TI - Pathogenesis of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia and
mechanisms underlying its relapse.
AB - ETV6/RUNX1 (E/R) is the most common fusion gene in childhood acute lymphoblastic
leukemia (ALL). Multiple lines of evidence imply a "two-hit" model for the
molecular pathogenesis of E/R-positive ALL, whereby E/R rearrangement is followed
by a series of secondary mutations that trigger overt leukemia. The cellular
framework in which E/R arises and the maintenance of a pre-leukemic condition by
E/R are fundamental to the mechanism that underlies leukemogenesis. Accordingly,
a variety of studies have focused on the relationship between the clones giving
rise to the primary and recurrent E/R-positive ALL. We review here the most
recent insights into the pathogenic mechanisms underlying E/R-positive ALL, as
well as the molecular abnormalities prevailing at relapse.
PMID- 28418911
TI - Elevated serum level of pancreatic stone protein/regenerating protein (PSP/reg)
is observed in diabetic kidney disease.
AB - : Diabetic kidney disease (DKD) is a major complication of diabetes, and serves
as an important cause of end-stage renal disease (ESRD). The role of chronic
inflammation in DKD is becoming widely accepted. Pancreatic stone
protein/regenerating protein (PSP/reg) is a secretory protein, which is elevated
in blood during infected conditions and organ failure. The aim of this study was
to investigate the relationship between serum PSP/reg and DKD in patients with
type 2 diabetes (T2DM). A total of 120 subjects which includes newly diagnosed
T2DM patients, diabetes patients without DKD, DKD patients, as well as healthy
controls were enrolled in this study. Serum PSP/reg levels were significantly
higher in DKD subjects compared with those of healthy controls (p < 0.001), newly
diagnosed T2DM (p < 0.001) and diabetes patients without DKD (p < 0.001). PSP/reg
levels correlated positively with glycated hemoglobin (HbA1c) (p < 0.001) and
serum creatinine (p < 0.001). Meanwhile, serum PSP level was negatively
correlated with estimated glomerular filtration rate (eGFR) (p < 0.001). The area
under the curve (AUC) for presence of DKD was 0.854. IN CONCLUSION: PSP/reg
levels are significantly up-regulated in DKD patients and might be related to
renal injury. A follow-up study with a large cohort is needed.
PMID- 28418910
TI - Erythropoietin drives breast cancer progression by activation of its receptor
EPOR.
AB - Breast cancer is a leading cause of cancer-related deaths. Anemia is common in
breast cancer patients and can be treated with blood transfusions or with
recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical
studies have indicated decreased survival in some groups of cancer patients
treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a
risk that EPO treatment would enhance tumor growth, but the mechanisms involved
in breast tumor progression are poorly understood.Here, we have examined the
functional role of the EPO-EPOR axis in pre-clinical models of breast cancer. EPO
induced the activation of PI3K/AKT and MAPK pathways in human breast cancer cell
lines. EPOR knockdown abrogated human tumor cell growth, induced apoptosis
through Bim, reduced invasiveness, and caused downregulation of MYC expression.
EPO-induced MYC expression is mediated through the PI3K/AKT and MAPK pathways,
and overexpression of MYC partially rescued loss of cell proliferation caused by
EPOR downregulation. In a xenotransplantation model, designed to simulate
recombinant EPO therapy in breast cancer patients, knockdown of EPOR markedly
reduced tumor growth.Thus, our experiments in vitro and in vivo demonstrate that
functional EPOR signaling is essential for the tumor-promoting effects of EPO and
underline the importance of the EPO-EPOR axis in breast tumor progression.
PMID- 28418912
TI - Human microRNA expression in sporadic and FAP-associated desmoid tumors and
correlation with beta-catenin mutations.
AB - Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging
histological diagnosis. DTs can occur sporadically or associated with the
familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with
beta-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease.
microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile
was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens
of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred
and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP
associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then
validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with
healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational
status in sporadic DTs. The correlation between sporadic DTs and miRNA expression
showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p
was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3,
as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was
also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect
the genesis and the progression of this disease and help histological diagnosis
of sporadic DTs.
PMID- 28418913
TI - Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of
IL-6 correlates with poor prognosis in bladder cancer.
AB - Bladder cancer (BC) is one of the most commonly occurring cancers, with a high
recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here,
we analyzed the markers and significance of myeloid-derived suppressor cells
(MDSCs) for BC development and progression. MDSC markers were examined in
peripheral blood from 113 BC patients and 20 healthy volunteers. We identified
CD11b+CD33lowHLA-DR- CD3- cells as markers of MDSCs in peripheral blood from BC
patients. We also demonstrated that MDSC numbers are higher in BC patients than
healthy donors, and that MDSC numbers correlate with the clinical grade, stage,
and poor prognosis. In addition, serum IL-6 levels are decreased in BC patients
with higher MDSC counts. IL-6 blockade increases induction of MDSCs in vitro. Low
IL-6 levels inhibit activation of Stat3, resulting in the increased formation of
MDSCs in BC. These results indicate that the MDSCs numbers may serve as a novel
prognostic marker in BC patients, and that targeting IL-6 signaling may be a
promising strategy for BC treatment.
PMID- 28418914
TI - MET exon 14 mutations as targets in routine molecular analysis of primary
sarcomatoid carcinoma of the lung.
AB - MET exon 14 splicing mutations are new targetable oncogenic drivers reported in
3% of non-small cell lung cancer (NSCLC) cases and have been shown to be more
common in pulmonary sarcomatoid carcinomas (PSCs). This study sought to screen
mutations affecting MET exon 14 splice sites in a large SC cohort of Caucasian
patients, with a large adenocarcinoma cohort as internal control.We tested 81
patients with SC and 150 with adenocarcinoma for splice site DNA mutations
leading to RNA splicing-based skipping of MET exon 14. To this end, we employed a
mass spectrometry-based custom-designed PCR assay for routine analysis of whole
MET exon 14 and flanking intronic regions using formalin-fixed paraffin-embedded
(FFPE) tumor samples.Our results revealed a 4.9% mutation rate for MET exon 14
mutations in Caucasian SC patients, which is, though highly variable, within the
usual range reported in NSCLC. Discrepancies with previous results reported in SC
could be accounted for the small number of cases, ethnicity, epithelial
component, and percentage of other driver mutations, such as KRAS, in the patient
populations studied. Based on our study findings, SC patients should be screened
for MET exon 14 mutations in the same manner as adenocarcinoma patients.
PMID- 28418916
TI - Clinicopathologic study of invasive micropapillary carcinoma of the breast.
AB - Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma.
It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though
it is uncertain whether the prognoses of IMPC and IDC differ. In this
retrospective study, we compared the clinicopathologic characteristics and
survival between 170 female patients with IMPC (pure or mixed with IDC) and 728
with pure IDC. The IMPC patients had higher clinical stages and histologic
grades, higher incidences of lymphovascular invasion and axillary lymph node
extracapsular extension, and a higher degree of lymph node involvement than IDC
patients. Moreover, IMPC was associated with increases in estrogen receptor (ER)
and progesterone receptor (PR) positivity and HER-2 overexpression. Although
locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS)
were poorer in IMPC patients than IDC patients, overall survival and distant
metastasis survival did not differ between the two groups. Multivariate analysis
revealed that IMPC was an independent prognostic factor for LRRFS in breast
cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer
RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment
decisions, patients with breast carcinoma be tested for the presence of this
specific subtype.
PMID- 28418915
TI - MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small
cell lung cancer.
AB - The present study assessed the role of metastasis-associated protein 1 (MTA1) in
epithelial to mesenchymal transition (EMT) and metastasis in non-small-cell lung
cancer (NSCLC) cells using a normal lung epithelium cell line, three NSCLC cell
lines, a mouse NSCLC model, and 56 clinical NSCLC samples. We observed that MTA1
overexpression decreased cellular adhesion, promoted migration and invasion, and
changed cytoskeletal polarity. MTA1 knockdown had the opposite effects. MTA1
overexpression decreased E-cadherin, Claudin-1, and ZO-1 levels and increased
Vimentin expression in vitro and in vivo, through activation of AKT/GSK3beta/beta
catenin signaling. However, treatment with the AKT inhibitor MK2206 did not
completely rescue effects associated with MTA1 expression changes, indicating
that pathways other than the AKT/GSK3beta/beta-catenin pathway could be involved
in MTA1-induced EMT. Compared with normal lung tissues, MTA1 expression was
elevated in NSCLC patient tissues and was correlated with American Joint
Committee on Cancer stage, T stage, lymphatic metastasis, and patient overall
survival. Additionally, MTA1 expression was positively associated with p-AKT and
cytoplasmic beta-catenin levels. These findings indicate MTA1 promotes NSCLC cell
EMT and metastasis via AKT/GSK3beta/beta-catenin signaling, which suggests MTA1
may be an effective anti-NSCLC therapeutic target.
PMID- 28418917
TI - Expression of guanylyl cyclase C in tissue samples and the circulation of rectal
cancer patients.
AB - Guanylyl cyclase C (GCC) is a transmembrane surface receptor restricted to
intestinal epithelial cells, from the duodenum to the rectum. We compared GCC
expression in tumors and normal rectal tissues, and investigated the relation
between GCC expression and metastasis and long-term survival of rectal cancer
patients. Based on the UICC classification, 42 rectal cancer patients in this
study were classified as stage I, 48 patients as stage II, and 90 patients as
stage III. Overexpression of GCC was observed in 80 rectal tumors as compared to
matched normal tissues, where no strong staining of GCC was observed. An
association between GCC mRNA in the circulation and tumor emboli in vessels, CK20
mRNA, distant organ metastasis, and survival status was observed in 100 rectal
cancer patients. Univariate Cox regression analysis indicated that tumor emboli
in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC
mRNA correlated with 5-year disease-free survival (DFS); while lymph node
metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall
survival (OS). In a multivariate Cox regression model, GCC mRNA level and
mesenteric root lymph node metastasis associated with DFS, while GCC mRNA levels
associated with OS. Quantification of GCC expression in circulation is a valuable
biomarker for assessing tumor burden and predicting outcome in rectal cancer
patients.
PMID- 28418918
TI - The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in
advanced gastric signet-ring cell carcinoma, representing a potential biomarker
for immunotherapy.
AB - Recent data supports a potentially significant role for immune checkpoint
inhibitors in the treatment of gastric cancer. However, there are few data on the
clinical implications of immunotherapy markers in gastric signet-ring cell
carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1
(PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell,
microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the
relationship of each factor to survival in 89 advanced SRCC patients. All
patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were
expressed in 40.4% and 18.0% of the patients, respectively. There was a
significant correlation between PD-L1 and PD-1 expression (r=0.363, p<0.001).
There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins
in 32.6% of samples. Only 1 case out of 89 was EBV positive, with concurrent PD
L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+
T cells numbers was associated with increased PD-1 expression (r=0.256, p=0.012)
and MSI status (r=0.208, p=0.049). High CD3+ T cell infiltration was related to
better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0,
p=0.033), but was not an independent prognostic factor for survival after
multivariate analysis (HR=0.68, 95% CI: 0.42-1.10, p=0.116). CD3+ T cell was more
infiltrated in PD-1 positive, tumors with MSI and were associated with better OS,
indicating an adaptive immune resistance may be occurring. Further research into
the cancer immunotherapy markers of SRCC immune microenvironment may highlight
targets for immunotherapy.
PMID- 28418919
TI - ZNF452 facilitates tumor proliferation and invasion via activating AKT-GSK3beta
signaling pathway and predicts poor prognosis of non-small cell lung cancer
patients.
AB - ZNF452 is a zinc-finger protein family member which contains an isolated SCAN
(SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN
N-terminus domain is known to play a role in transcriptional regulation of genes
involved in cell survival and differentiation, there are no precise cellular
functions that have been assigned to ZNF452. In the present study, we found that
either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC
cells and positive ratio of ZNF452 in NSCLC samples (50.8%, 93/183) was
significantly higher than that in normal lung tissues (22.4%, 13/58, P<0.001).
ZNF452 overexpression was correlated with advanced TNM stage (P=0.033), positive
lymph node metastasis (P=0.002) and predicted poor overall survival of NSCLC
patients (P<0.001). ZNF452 facilitated tumor growth, colony formation, G1-S phase
arrest, migration and invasion through upregulating the levels of CyclinD1,
CyclinE1, p-Rb, or Snail, and downregulating the expression of Zo-1. In nude mice
xenografts, overexpressing ZNF452 also promoted tumor proliferation and
metastasis. Subsequently, we found that the effect of ZNF452 on facilitating
tumor proliferation and invasion was through activating its downstream AKT
GSK3beta signaling pathway. Treatment of AKT inhibitor markedly prevented the
phosphorylation of AKT and GSK3beta which subsequently counteracted increasing
expression of CyclinD1, CyclinE1 or Snail and restored the decreasing expression
of Zo-1, as well as the upregulation of tumor proliferation and invasion, caused
by ZNF452 overexpression.Taken together, the present study indicated that ZNF452
may be an upstream regulator of AKT-GSK3beta signaling pathway and facilitates
proliferation and invasion of NSCLC.
PMID- 28418920
TI - Complementary utility of targeted next-generation sequencing and
immunohistochemistry panels as a screening platform to select targeted therapy
for advanced gastric cancer.
AB - We tested the clinical utility of combined profiling of Ion Torrent PGM based
next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to
molecularly targeted therapies. A consecutive cohort of 93 patients with
advanced/metastatic GC who underwent palliative chemotherapy between March and
December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor
biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding
RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2,
MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53
protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay).
Treatment was based on availability of targeted agents at the time of molecular
diagnosis. Among the 81 cases with available tumor samples, complete NGS and IHC
profiles were successfully achieved in 66 cases (81.5%); only IHC results were
available for 15 cases. Eight cases received matched therapy based on sequencing
results; ERBB2 amplification, trastuzumab (n = 4); PIK3CA mutation, Akt inhibitor
(n = 2); and FGFR2 amplification, FGFR2b inhibitor (n = 2). Eleven cases received
matched therapy based on IHC; ERBB2 positivity, trastuzumab (n = 5); PTEN loss (n
= 2), PI3Kbeta inhibitor; MMR deficiency (n = 2), PD-1 inhibitor; and EGFR
positivity (n = 2), pan-ERBB inhibitor. A total of 19 (23.5%) and 62 (76.5%)
cases were treated with matched and non-matched therapy, respectively. Matched
therapy had significantly higher overall response rate than non-matched therapy
(55.6% vs 13.1%, P = 0.001). NGS and IHC markers provide complementary utility in
identifying patients who may benefit from targeted therapies.
PMID- 28418922
TI - Novel impact of the DNMT3A R882H mutation on GSH metabolism in a K562 cell model
established by TALENs.
AB - DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid
leukemia (AML) patients, and were considered to be an adverse prognostic factor
for adult de novo AML cases. However, the relevant molecular mechanism of the
mutation in AML pathogenesis remains obscure. In this study, we established K562
and SKM1 cell model carrying the DNMT3A R882H mutation via transcription
activator-like effector nuclease (TALEN) and Clustered regularly interspaced
short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated
DNMT3A could promote the proliferative capability of malignant cell clones.
Further RNA microarray analysis revealed that some genes crucial for glutathione
(GSH) synthesis, including CTH, PSPH, PSAT1 and especially SLC7A11 (the
cysteine/glutamate transporter) were significantly up-regulated, which resulted
in significant elevation of intracellular GSH levels. A subsequent experiment
demonstrated that the mutant clones are resistant to chemotherapy as well as
SLC7A11-inhibitorsBy shRNA induced SLC7A11 silencing, we discovered profoundly
decreased cellular GSH and cell proliferative ability of DNMT3A mutated clones.
Our results provided novel insight into the role of the DNMT3A R882H mutation in
AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway
could enhance the current therapy for AML patients with the DNMT3A R882H
mutation.
PMID- 28418923
TI - OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3
signaling.
AB - Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of
death worldwide. Since there is a dire need for novel and effective therapies to
improve the poor survival rates of advanced pancreatic cancer patients, we
analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on
pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger
antitumor effect than gemcitabine on two pancreatic cancer cell lines, including
gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down
regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and
decreased phosphorylation of JAK and STAT3. Cell migration and invasiveness
assays showed that OSU-A9 reduced cancer cell aggressiveness and inhibited BxPC-3
xenograft growth in nude mice. These results suggest that OSU-A9 modulates the
p38-JAK-STAT3 signaling module, thereby inducing cytotoxicity in pancreatic
cancer cells. Continued evaluation of OSU-A9 as a potential therapeutic agent for
pancreatic cancer thus appears warrented.
PMID- 28418924
TI - RNA sequencing analyses reveal novel differentially expressed genes and pathways
in pancreatic cancer.
AB - Gene expression microarrays have identified many tumor markers and therapeutic
targets for pancreatic ductal adenocarcinoma (PDAC). However, microarray
profilings have limited sensitivity and are prone to cross-hybridization between
homologous DNA fragments. Here, we perform a transcriptome analysis of paired
tumor and adjacent benign pancreatic tissues from 10 patients who underwent
resection for PDAC. We identify a total of 2736 differentially expressed genes
(DEGs) with false discovery rate less than 0.05, including 1554 upregulated, 1182
downregulated, and 6 microRNAs (miR-614, miR-217, miR-27b, miR-4451, miR-3609,
and miR-612). Overexpression of five DEGs, i.e. KRT16, HOXA10, CDX1, SI, and
SERPINB5 in tumors is confirmed by RT-PCR in 20 additional tissues.
Overexpression of KRT16 in PDAC is also verified on protein level. In addition,
top canonical pathways such as granulocyte adhesion and diapedesis pathway have
been identified. Our study represents a comprehensive characterization of the
PDAC transcriptome and provides insight to the mechanisms of pancreatic
carcinogenesis and potential biomarkers and novel therapeutic targets for
pancreatic cancer.
PMID- 28418925
TI - Syntenin promotes VEGF-induced VEGFR2 endocytosis and angiogenesis by increasing
ephrin-B2 function in endothelial cells.
AB - Syntenin, a tandem PDZ-domain-containing scaffold protein, is involved in the
regulation of diverse biological functions, including protein trafficking,
exosome biogenesis, and cancer metastasis. Here, we present the first study to
explore the significance of syntenin in endothelial cells. Syntenin knockdown in
human umbilical vein endothelial cells (HUVECs) impaired vascular endothelial
growth factor (VEGF)-mediated proliferation, migration, invasion, vascular
permeability, and nitric oxide (NO) production. Syntenin knockdown also
suppressed expression of the VEGFR2 target genes VEGF, MMP2, and Nurr77 as well
as VEGF-induced angiogenesis in vitro and in vivo. And it decreased cell-surface
levels of ephrin-B2. Biochemical analyses revealed that syntenin exists in
complex with VEGFR2 and ephrin-B2. Syntenin knockdown abolished the association
between VEGFR2 and ephrin-B2, suggesting syntenin functions as a scaffold protein
facilitating their association in HUVECs. Consistent with these observations,
knocking down syntenin or ephrin-B2 abolished VEGF-induced endocytosis and VEGFR2
phosphorylation and activation of its downstream signaling molecules. Treatment
with MG132, a proteasome inhibitor, rescued the downregulation of ephrin-B2 and
VEGFR2 signaling induced by syntenin knockdown. These findings demonstrate that
syntenin promotes VEGF signaling and, through its PDZ-dependent interaction with
ephrin-B2, enhances VEGF-mediated VEGFR2 endocytosis and subsequent downstream
signaling and angiogenesis in endothelial cells.
PMID- 28418926
TI - Urinary kallikrein 10 predicts the incurability of gastric cancer.
AB - The current imaging modalities are not sufficient to identify inoperable tumor
factors, including distant metastasis and local invasion. Hence, we conducted
this study using urine samples to discover non-invasive biomarkers for the
incurability of gastric cancer (GC). Urine samples from 111 GC patients were
analyzed in this study. The GC cohort was categorized and analyzed according to
disease stage and operability. In the discovery phase, protease protein array
analysis identified 3 potential candidate proteins that were elevated in the
urine of advanced GC patients compared to early GC patients. Among them, urinary
kallikrein 10 (KLK10) was positively associated with tumor stage progression.
Moreover, the urinary level of KLK10 (uKLK10) was significantly elevated in the
urine of patients with inoperable GC compared to operable GC patients (median,
118 vs. 229; P=0.014). The combination of uKLK10, tumor location and tumor size
distinguished operability of GC with an area under the curve of 0.859, 82.4%
sensitivity and 86.2% specificity. Disease-free survival (DFS) was significantly
shorter in GC patients with high uKLK10 compared to those with low uKLK10 (hazard
ratio: 3.30 [95% confidence interval, 1.58-6.90] P<0.001). Immunohistochemical
analyses also demonstrated a positive correlation between tumor stage and KLK10
expression in GC tissues (r=0.426, P<0.001). In addition, GC patients with high
expression of pathological KLK10 (pKLK10) showed a significantly shorter DFS
compared to those with low pKLK10 (hazard ratio: 3.79 [95% confidence interval,
1.27-11.24] P=0.010). uKLK10 is a promising non-invasive biomarker for the
inoperability and incurability of GC.
PMID- 28418927
TI - Transarterial chemoembolization combined with computed tomography-guided
125iodine implantation enhances survival in hepatocellular carcinoma patients
with portal vein tumor thrombus.
AB - We conducted a retrospective study to evaluate the safety and efficacy of
transarterial chemoembolization (TACE) combined with computed tomography-guided
125iodine implantation (TACE-125iodine) in hepatocellular carcinoma (HCC)
patients with type B portal vein tumor thrombus (PVTT). From medical records, we
determined that 50 patients who received 125iodine implantation 4-7 days after
the first TACE session showed better survival than 50 patients who received only
TACE (median survival, 13.1 vs. 6.0 months; P<0.01). Moreover, the PVTT control
rate was higher in the TACE-125iodine than TACE alone group (78% vs. 18%;
P<0.01). Multivariate analysis demonstrated that the TACE-125iodine procedure was
an independent prognostic factor for overall survival. We also observed that
bilirubin levels were increased at 4 weeks, indicating that 125iodine seeding in
the PVTT beneficially impacted the small bile duct, which is proximal to the
portal vein. No severe adverse events were observed in patients that received
125iodine seed implantation, and the mild adverse events were successfully
treated. This study shows that TACE-125iodine therapy enhances patient survival
with minimal adverse events. It is also more affordable than sorafenib, which is
currently the recommended therapy for advanced HCC patients with PVTT.
PMID- 28418928
TI - ERK signalling modulates epigenome to drive epithelial to mesenchymal transition.
AB - The series of events that allow the conversion from adherent epithelial cells
into migratory cells is collectively known as epithelial-mesenchymal transition
(EMT). EMT is employed during embryonic development such as for gastrulation and
neural crest migration and is misused in diseases, such as cancer metastasis. ERK
signalling is known to be essential for EMT, however its influence on the
epigenetic and transcriptional programme underlying EMT is poorly understood.
Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene
expression in mammary epithelial cells undergoing EMT, we found that ERK
signalling is essential for the epigenetic reprogramming underlying hallmark gene
expression and phenotypic changes of EMT. We show that the chemical inhibition of
Erk signalling during EMT prevents the loss and gain of the H3K27ac mark at
regulatory regions of epithelial and mesenchymal genes, respectively, and results
in a transcriptome and epigenome closer to those of epithelial cells. Further
computational analyses identified a distinct set of transcription factor motifs
enriched at distal regulatory regions that are epigenetically remodelled by ERK
signalling. Altogether, our findings reveal an ERK-dependent epigenetic
remodelling of regulatory elements that results in a gene expression programme
essential for driving EMT.
PMID- 28418929
TI - Plurihormonal cells of normal anterior pituitary: Facts and conclusions.
AB - INTRODUCTION: plurihormonality of pituitary adenomas is an ability of adenoma
cells to produce more than one hormone. After the immunohistochemical analysis
had become a routine part of the morphological study, a great number of adenomas
appeared to be multihormonal in actual practice. We hypothesize that the same
cells of a normal pituitary gland releases several hormones simultaneously.
OBJECTIVE: To analyse a possible co-expression of hormones by the cells of the
normal anterior pituitary of adult humans in autopsy material. MATERIALS AND
METHODS: We studied 10 pituitary glands of 4 women and 6 men with cardiovascular
and oncological diseases. Double staining immunohistochemistry using 11 hormone
combinations was performed in all the cases. These combinations were:
prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH),
prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic
hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH,
TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies
was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin,
TSH/prolactin, ACTH/GH, and FSH/GH. RESULTS: We found that the same cells of the
normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with
ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co
expression coefficients of prolactin, GH and TSH with other hormones showed that
the TSH co-expression coefficient was significantly the least (9,5+/-6,9%; 9,6+/
7,8%; 1,0+/-1,3% correspondingly). CONCLUSION: Plurihormonality of normal
adenohypophysis is an actually existing phenomenon. Identification of different
hormones in pituitary adenomas enables to find new ways to improve both
diagnostic process and targeted treatment.
PMID- 28418930
TI - The innate immunity of guinea pigs against highly pathogenic avian influenza
virus infection.
AB - H5N1 avian influenza viruses are a major pandemic concern. In contrast to the
highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs
do not typically display signs of severe disease in response to H5N1 virus
infection. Here, proteomic and transcriptional profiling were applied to identify
host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002
(H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes
were among host proteins with altered expression in guinea pig lungs during H5N1
infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea
pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was
required for RIG-I mediated inhibition of viral replication upstream of the
activity of MAVS. Furthermore, we show that guinea pig complement is involved in
viral clearance, the regulation of inflammation, and cellular apoptosis during
influenza virus infection of guinea pigs. This work uncovers features of the
guinea pig innate immune response to influenza that may render guinea pigs
resistant to highly pathogenic influenza viruses.
PMID- 28418931
TI - SOCS3 treatment prevents the development of alopecia areata by inhibiting CD8+ T
cell-mediated autoimmune destruction.
AB - Alopecia areata is one of the most common autoimmune diseases resulting from T
cell-mediated damage of hair follicles. CD8+ T cells infiltrate hair follicles
and are responsible for destruction of hair follicles. However the underlying
mechanisms for hair loss remain still obscure. In the present study, we
identified that suppressor of cytokine signaling-3 (SOCS3), a classical inhibitor
of cytokine signaling, significantly inhibits CD8+T cell maturation, interferon
gamma (IFN-gamma) production and alopecia areata. SOCS3 is downregulated in the
skin of alopecia areata patients and murine autoimmune alopecia model.
Furthermore, SOCS3 treatment prevents the development of alopecia areata in the
graft model. SOCS3 decreases the CD44high CD62Llow effector memory CD8+ T cells,
resulting in the decrease of IFN-gamma production. The expression of Fas and
major histocompatibility complex-1 (MHC I) is upregulated in skin from C3H/HeJ
alopecia areata mice, and this increase is suppressed by SOCS3. The SOCS3 level
is negative correlation with the Fas and MHC I level in patients with alopecia
areata. These results suggest that SOCS3 treatment may be an effective strategy
to treat autoimmune alopecia as well as to more generally prevent cytokine
dependent tissue destruction in inflammatory diseases.
PMID- 28418932
TI - BMPR1B mutation causes Pierre Robin sequence.
AB - BACKGROUND: We investigated a large family with Pierre Robin sequence (PRS). AIM
OF THE STUDY: This study aims to determine the genetic cause of PRS. RESULTS: The
reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS
in a three-generation family. Whole-genome sequencing and Sanger sequencing
successfully detected breakpoints in the intragenic regions of BMRP1B and GRM4.
We hypothesized that PRS in this family was caused by (i) haploinsufficiency for
BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion
gene. In an unrelated family, we identified another BMPR1B-splicing mutation that
co-segregated with PRS. CONCLUSION: We detected two BMPR1B mutations in two
unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of
human PRS. METHODS: GTG banding, comparative genomic hybridization, whole-genome
sequencing, and Sanger sequencing were performed to identify the gene causing
PRS.
PMID- 28418934
TI - Chromosome analysis in a case of a plutonium contaminated wound.
AB - Chromosome analysis of peripheral blood lymphocytes was undertaken over a 10 year
period following an intake of plutonium through a hand wound. Frequencies of
cells with unstable complex aberrations remained high throughout this time,
probably reflecting direct exposure of lymphocytes as they passed plutonium which
had transferred to regional lymph nodes. Analysis at the final sampling time also
revealed cells with stable aberrations at a much higher frequency relative to the
number of unstable cells than expected from direct exposure, and is therefore
most likely to be reflecting exposure to lymphocyte precursor cells from
plutonium that has become deposited on bone surfaces.
PMID- 28418933
TI - Genetic variation of long non-coding RNA TINCR contribute to the susceptibility
and progression of colorectal cancer.
AB - Colorectal cancer (CRC) accounts for the leading causes of cancer-related
morbidity and mortality. However, a large part of heritable factors are warranted
to be explored. Long non-coding RNAs (lncRNAs) serve critical roles in cancer
development and progression. Herein, we explored effect of genetic variants of
Tissue differentiation-inducing non-protein coding RNA (TINCR), a key lncRNA
required for somatic tissue differentiation and tumor progression, on risk and
progression of CRC. Three tagSNPs, including rs2288947, rs8105637, and
rs12610531, were evaluated in in a two-stage, case-control study. Two SNPs,
rs2288947 and rs8105637, were significantly associated with susceptibility of CRC
in both stages. When pooled together, the allele G was significantly associated
with 23% decreased risk of CRC (OR=0.77; 95% CI=0.67-0.88; P value = 1.2*10-4)for
SNP rs2288947. While for SNP rs8105637, the allele A was significantly associated
with 22% increased risk of CRC (OR=1.22; 95% CI=1.09-1.37; P value = 6.2*10-4).
The two SNPs were also statistically associated with occurrence of lymph node
metastasis of CRC. The carriers of allele G are less likely to get lymph node
metastasis (OR=0.77; 95% CI=0.63-0.94; P value = 0.011) for rs2288947, and the
carriers of allele A are more likely to get lymph node metastasis (OR=1.22; 95%
CI=1.03-1.43; P value = 0.019) for rs8105637. These results suggest that lncRNA
TINCR polymorphisms may be implicated in the development and progression of CRC.
PMID- 28418935
TI - Aluminum/vacuum multilayer configuration for spatial high-energy electron
shielding via electron return effects induced by magnetic field.
AB - Radiation shielding of high-energy electrons is critical for successful space
missions. However, conventional passive shielding systems exhibit several
limitations, such as heavy configuration, poor shielding ability, and strong
secondary bremsstrahlung radiation. In this work, an aluminum/vacuum multilayer
structure was proposed based on the electron return effects induced by magnetic
field. The shielding property of several configurations was evaluated by using
the Monte Carlo method. Results showed that multilayer systems presented improved
shielding ability to electrons, and less secondary x-ray transmissions than those
of conventional systems. Moreover, the influences of magnetic flux density and
number of layers on the shielding property of multilayer systems were
investigated using a female Chinese hybrid reference phantom based on cumulative
dose. In the case of two aluminum layers, the cumulative dose in a phantom
gradually decreased with increasing magnetic flux density. The maximum decline
rate was found within 0.4-1 Tesla. With increasing layers of configuration, the
cumulative dose decreased and the shielding ability improved. This research
provides effective shielding measures for future space radiation protection in
high-energy electron environments.
PMID- 28418936
TI - Deposition and spatial variation of thoron decay products in a thoron
experimental house using the Direct Thoron Progeny Sensors.
AB - Experiments have been carried out using the deposition-based Direct Thoron
Progeny Sensors (DTPS) in a thoron experimental house. The objective was to study
the thoron decay product characteristics such as the deposition velocities,
spatial variability and dependence on aerosol particle concentrations. Since the
deposition velocity is an important characteristic in the calibration of the
DTPS, it is very important to study its dependence on aerosol concentration in a
controlled environment. At low aerosol concentration (1500 particles/cm3) the
mean effective deposition velocity was measured to be 0.159 +/- 0.045 m h-1; at
high aerosol concentration (30 000 particles/cm3) it decreased to 0.079 +/- 0.009
m h-1. The deposition velocity for the attached fraction of the thoron decay
products did not change with increasing aerosol concentration, showing
measurement results of 0.048 +/- 0.005 m h-1 and 0.043 +/- 0.014 m h-1,
respectively. At low particle concentration, the effective deposition velocity
showed large scattering within the room at different distances from center. The
attached fraction deposition velocity remained uniform at different distances
from the wall. The measurements in the thoron experimental house can be used as a
sensitivity test of the DTPS in an indoor environment with changing aerosol
concentration. The uniform spatial distribution of thoron decay products was
confirmed within the experimental house. This indicates that direct measurement
of thoron decay product concentration should be carried out instead of inferring
it from thoron gas concentration, which is very inhomogeneous within the
experimental house.
PMID- 28418937
TI - Clinical validation of a new wrist continuous noninvasive hemodynamic monitoring
system in comparison with invasive radial artery measurement.
AB - BACKGROUND: An ideal arterial pressure monitoring system for perioperative care
is required to be accurate, noninvasive, continuous, and risk free. Although
several continuous noninvasive arterial pressures (CNAP) are determined on the
finger, a new wrist CNAP monitoring system was developed. This prospective study
was designed as a randomized-controlled trial to assess its validity in
comparison with invasive arterial pressure (IAP) monitoring. PATIENTS AND
METHODS: Sixty patients undergoing elective surgery under general anesthesia were
enrolled. One-side arm in each patient was selected randomly to assess the new
monitoring system placed on the wrist; an arterial catheter for IAP was inserted
at the radial artery in the contralateral arm. The Bland-Altman method for
repeated measurements was used to assess agreement between measurement methods by
the levels of agreement according to the American Association for the Advancement
of Medical Instrumentation standards. RESULTS: A total of 6600 valid pressure
readings were obtained from 60 patients, including 3000 beat data and 3600 pulse
wave data, respectively. The mean differences in wrist CNAP versus IAP for beat
data were as follows: systolic arterial pressure (SAP): -2.09+/-5.39 mmHg; mean
arterial pressure (MAP): 0.27+/-3.64 mmHg; diastolic arterial pressure (DAP): and
2.63+/-6.44 mmHg. For pulse wave data, the mean difference (SD) values were as
follows: SAP: -2.06+/-6.51 mmHg; MAP: 0.50+/-4.36 mmHg; and DAP: 3.06+/-6.81
mmHg. Percentage errors were less than 28.3%. Levels of agreements were detected
to be -12.65-8.47 for SAP, -6.86-7.40 for MAP, and -9.99-15.26 for DAP.
CONCLUSION: The new wrist CNAP monitoring system showed an acceptable agreement
and interchangeability with the IAP.
PMID- 28418938
TI - A Study on Postmortem Wound Dating by Gross and Histopathological Examination of
Abrasions.
AB - INTRODUCTION: Abrasions are the most common blunt force injuries. The precise
dating of injury is extremely important in forensic medicine practice. As we
know, the wound healing occurs in well-orchestrated sequence, consisting of
inflammation, proliferation, and maturation.A study of occurrence of such phases
will help in understanding the sequence of events in wound healing. In this
context, this study of wound dating from gross and microscopic level was taken.
MATERIALS AND METHODS: Postmortem study of wound dating by gross and
histopathological examination of abrasions was carried out in the Department of
Forensic Medicine, in M.S. Ramaiah Medical College. A total of 101 abrasions were
correlated to time frame the occurrence of different gross changes and
microscopic changes that follow the blunt trauma. Abrasions ranging from 0 hour
to a maximum of 45 days were studied. RESULTS: The gross changes of abrasions
were in correlation with the microscopic changes; however, the role of the
comorbid conditions is significant because the results showed variations with
respect to healing process. CONCLUSIONS: This study signifies that, if naked eye
examination is studied along with histopathological examination, the reliability
and accuracy of dating of wound increase. Whenever accurate determination of age
is required, the autopsy surgeon can subject the samples for histopathological
examination and correlate before opining the age of injury.
PMID- 28418939
TI - Exploring the molecular pathogenesis and biomarkers of high risk oral
premalignant lesions on the basis of long noncoding RNA expression profiling by
serial analysis of gene expression.
AB - Oral premalignant lesions (OPLs) have malignant transformation potential, with no
reliable markers available. This study aimed to assess molecular events to
identify biomarkers that can reflect high-risk lesions as predictive factors to
tailor clinical decision for patients on the basis of long noncoding RNAs
(lncRNA) expression profiling by serial analysis of gene expression. The GSE31021
and GSE8127 datasets were downloaded from the Gene Expression Omnibus database.
Differentially expressed genes (DEGs) and lncRNAs were identified using the LIMMA
package in R language. The genes targeted by lncRNAs were predicted among
screened DEGs using Pearson's correlation. Gene ontology function and Kyoto
Encyclopedia of Genes and Genomes pathway analyses were carried out for genes
targeted by lncRNAs using the Database for Annotation, Visualization, and
Integrated Discovery online tool. A total of 674 DEGs and differentially
expressed lncRNAs were screened. Thirty-two interactions of 10 lncRNAs and 524
target genes were predicted. The lncRNA NEAT1 was among the top 10 lncRNAs. The
coregulated target genes RP4-684O24, RP11-283I3, and RP11-350G8 were
significantly enriched in the immune response and mannosyl-oligosaccharide
mannosidase activity. The target genes coregulated by LINC00665 and MIR378D2 were
significantly enriched in the ubiquitin-dependent protein catabolic process,
ubiquitin-protein ligase activity, and neurotrophin signaling. The lncRNA NEAT1
may play an important role in high-risk lesions. The novel lncRNAs and DEGs
identified in OPLs may mediate the immune response and neurotrophin signaling and
show ubiquitin ligase activity. These results improve our understanding of the
molecular pathogenesis of OPLs and identify some potential targets for early
diagnosis of high risk OPLs.
PMID- 28418940
TI - Assessment of the Albumin-Bilirubin (ALBI) Grade as a Prognostic Indicator for
Hepatocellular Carcinoma Patients Treated With Radioembolization.
AB - OBJECTIVE: As the utility of Child-Pugh (C-P) class is limited by the
subjectivity of ascites and encephalopathy, we evaluated a previously established
objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for
yttrium-90 radioembolization (RE) treatment for patients with hepatocellular
carcinoma (HCC). MATERIALS AND METHODS: A total of 117 patients who received RE
for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P
class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS)
according to these 3 criteria was evaluated by Kaplan-Meier survival analysis.
The utilities of C-P class and ALBI grade as prognostic indicators were compared
using the log-rank test. Multivariate Cox regression analysis was performed to
identify additional predictive factors. RESULTS: Patients with ALBI grade 1
(n=49) had superior OS than those with ALBI grade 2 (n=65) (P=0.01). Meanwhile,
no significant difference was observed in OS between C-P class A (n=100) and C-P
class B (n=14) (P=0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was
able to stratify 2 clear and nonoverlapping subgroups with differing OS curves
(P=0.03). Multivariate Cox regression test identified alanine transaminase,
Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic
factors for OS (P<0.10). CONCLUSIONS: ALBI grade as a prognosticator has
demonstrated clear survival discrimination that is superior to C-P class among
HCC patients treated with RE, particularly within the subgroup of C-P class A
patients. ALBI grade is useful for clinicians to make decisions as to whether RE
should be recommended to patients with HCC.
PMID- 28418941
TI - Prenatal fluoxetine modifies the behavioral and hormonal responses to stress in
male mice: role for glucocorticoid insensitivity.
AB - Women with major depressive disorder during pregnancy often use selective
serotonin reuptake inhibitors (SSRIs) antidepressants. These drugs readily cross
the placental barrier and impact the developing fetal brain. Recently, we
reported that prenatal fluoxetine (FLX), an SSRI antidepressant drug, altered
corticosterone and behavioral responses to stress in female mouse offspring. The
present study assessed the effects of prenatal FLX on these responses in males.
The results showed that prenatal FLX significantly augmented the corticosterone
response to acute stress in young prepubescent mice. The corticosterone response
to continuous stress was not affected by prenatal FLX irrespective of age. In
addition, continuous stress reduced general activity, and anxiety-like and
depressive-like behaviors in adult animals prenatally exposed to FLX, but not in
controls. The dexamethasone suppression test showed that prenatal FLX induced a
state of glucocorticoid insensitivity in adult males, indicating that the
negative feedback control of the hypothalamic-pituitary-adrenal axis response to
stress was disrupted. Together, these findings indicate that prenatal FLX altered
hormonal and behavioral responses to stress and suggest a role for the
development of glucocorticoid insensitivity in these effects. These findings may
aid understanding of the limitations and precautions that should be taken in the
use of SSRIs by pregnant women.
PMID- 28418942
TI - Response rate decreasing effects of naloxone during chronic sucrose availability.
AB - Studies in animal models suggest that sugar deprivation following excessive
intake elicits some opioid-like withdrawal signs. In the present study, opioid
like effects of excessive sucrose intake were further characterized in C57BL/6
mice by comparing the effects of the opioid antagonist naloxone on food
reinforced responding before and during sucrose availability and, in parallel
experiments, following chronic morphine administration. Results show that
naloxone produced time-dependent and dose-dependent decreases in operant response
rates after 4 weeks of excessive sucrose consumption, and that these effects were
comparable with those produced by chronic morphine injections. These findings
extend the observation that excessive sucrose consumption may produce opioid-like
withdrawal signs, and suggest that operant assays of withdrawal-suppressed
behaviors may be useful for further study of excessive sucrose consumption.
PMID- 28418943
TI - Loss of control over alcohol seeking in rats depends on individual vulnerability
and duration of alcohol consumption experience.
AB - Alcohol use disorder (AUD) is characterized by excessive alcohol use and
persistent alcohol seeking despite knowledge of its negative consequences.
Importantly, AUD typically develops after chronic excessive alcohol use in a
subgroup of individuals who drink alcohol, suggesting that AUD results from an
interaction between individual vulnerability and prolonged alcohol exposure. The
present study assessed the contribution of prolonged exposure to alcohol and
individual levels of alcohol intake to the development of loss of control over
alcohol seeking in a conditioned suppression model. To investigate the impact of
prolonged alcohol exposure, conditioned suppression of alcohol seeking was
assessed after 2 and 4 months of intermittent alcohol access (IAA) in a subgroup
of rats drinking moderate amounts of alcohol. We observed that suppression of
alcohol seeking was reduced after 4 months compared with 2 months of IAA. The
influence of individual levels of alcohol intake on loss of control over alcohol
seeking was subsequently determined by assessing conditioned suppression in
subgroups of low and high alcohol drinking rats. Unlike the low alcohol drinking
rats, the high alcohol drinking rats showed aversion-resistant alcohol seeking
after 2 months of IAA, although both groups showed comparable levels of
conditioned freezing. These findings show that the development of loss of control
over alcohol seeking, a key characteristic of AUD in humans, is dependent on both
the extent of alcohol exposure and the individual's propensity to consume
alcohol.
PMID- 28418944
TI - The Benefit of Pro Re Nata Antiemetics Provided With Guideline-Consistent
Antiemetics in Delayed Nausea Control.
AB - BACKGROUND: Delayed nausea after chemotherapy remains a symptom of interest.
Clinicians often provide additional and/or pro re nata (p.r.n.) antiemetics with
guideline-consistent antiemetics in an attempt to achieve further symptom
control. Whether the usage of additional and/or p.r.n. antiemetics provide added
benefit remains as a question. OBJECTIVE: The purpose of this study was to
determine the benefit of providing additional antiemetics and/or p.r.n.
antiemetics with guideline-consistent antiemetics in the control of nausea,
functioning, and quality of life (QOL). METHODS: A secondary data analysis of 143
breast cancer patients who received guideline-consistent antiemetics for
anthracycline and cyclophosphamide chemotherapy was conducted. Instruments
included vomiting frequency and nausea intensity items of the Multinational
Association of Supportive Care in Cancer Antiemesis Tool and the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
C30. RESULTS: Providing p.r.n. antiemetics alleviated the incidence of
significant nausea (intensity, >=3) in the delayed phase. The experience of
nausea contributed to symptom incidence in the next phase and cycle. The
intensity of delayed nausea demonstrated a moderate negative correlation with
physical and role functioning and global health/QOL. CONCLUSION: Providing
patients with strategies to further control nausea (p.r.n. antiemetics) in
addition to guideline-consistent antiemetics is recommended for practice. Because
the nausea experience contributes to symptom incidence in the next phase and
cycle and because the nausea intensity demonstrated a significant relationship
with function and global health/QOL, proactive supportive approaches are strongly
recommended. IMPLICATIONS FOR PRACTICE: Delayed nausea control may be improved by
adhering to guideline-consistent antiemetics and using p.r.n. antiemetics.
Delayed nausea control would contribute to patients' functioning and QOL.
PMID- 28418945
TI - Tendonitis and Tendon Rupture After Treatment With Rituximab: A Case Series.
AB - CLINICAL DATA: Rituximab is a mouse/human chimeric anti-CD20 IgG1 monoclonal
antibody used to treat cancer and autoimmune conditions. Side effects of
rituximab include fever, rash, cytopenia and hypotension, back pain, arthralgia,
and myalgia. Here, we report on 3 patients who developed moderate to severe
tendonitis after the second infusion of rituximab. THERAPEUTIC CHALLENGE: We
report 3 patients who developed tendonitis after the second infusion of
rituximab. These patients were undergoing treatment for connective tissue
diseases. All 3 patients received 2 rituximab infusions, 2 weeks apart. The 3
cases developed clinical tendonitis that was confirmed by magnetic resonance
imaging in 2 cases. INTERPRETATION: This is the first case series reporting new
onset tendonitis in patients with connective tissue diseases after rituximab
therapy. All 3 cases developed tendonitis 1 week after receiving the second dose
of rituximab. Clinical features of tendonitis resolved 3-4 months in all cases.
The underlying pathogenic mechanism by which rituximab causes tendonitis is not
clear, but tendonitis and tendon rupture have been reported after using other
medications such as quinolones. The tendon damage was progressive leading to
tendon rupture in 1 patient, highlighting the importance of early recognition. It
is plausible that there is a cause-effect relation between tendonitis and
administration of rituximab in our 3 cases, since none of these cases had
previous history of tendonitis; however, more data are needed to confirm this
observation.
PMID- 28418946
TI - A Case of Cyanosis: Dapsone Induced Methemoglobinemia and Coexisting Pulmonary
Embolism.
PMID- 28418947
TI - Sleep-Induced Apraxia of Eyelid Opening.
AB - BACKGROUND: Apraxia of eyelid opening (AEO) primarily has been described as
bilateral loss of volitional ability to open the eyes at certain times and often
associated with neurodegenerative disease. Rarely, it can occur in isolation and
as an idiopathic phenomenon. There are a few reports of unilateral AEO only on
awakening from sleep. We report an additional 11 patients with this unusual
variation of AEO. METHODS: Retrospective, observational case series of patients
collected from 3 separate neuro-ophthalmology practices. RESULTS: All 11 patients
were Caucasian women with a mean age of 59 years (range 35-80 years). All
experienced AEO on awakening from sleep. Eight patients had unilateral AEO, and 3
had bilateral symptoms. The duration of episodes ranged from 3 weeks to several
years. Ten of the patients reported manually elevating the eyelid to open it,
while 1 patient waited for the eyelid to open spontaneously. After initial manual
elevation, all patients reported normal function and position of the eyelids for
the remainder of the day. Seven patients had a history of autoimmune disease.
Slit-lamp and fundus examinations were negative for ocular pathology to explain
the patients' symptoms, and 9 patients had unremarkable brain imaging.
CONCLUSIONS: AEO occurring only on awakening from sleep is a rare entity.
Neuroimaging and extensive laboratory testing are not indicated without
associated neurologic or ocular findings. There may be a Caucasian female
preponderance and autoimmune link in patients with AEO, but further studies are
required.
PMID- 28418948
TI - Optical Coherence Tomography in Neuroretinitis: Epipapillary Infiltrates and
Retinal Folds.
AB - Neuroretinitis is a form of papillitis associated with the delayed onset of an
exudative macular star among other inflammatory ocular findings. We describe 4
patients with neuroretinitis who displayed several distinctive and novel findings
on spectral-domain optical coherence tomography (OCT) that include "epipapillary
infiltrates" and an atypical pattern of inner retinal folds. The recognition of
these findings on OCT may help in the early diagnosis of neuroretinitis.
PMID- 28418949
TI - Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac
Sarcoidosis and Myocarditis.
AB - PURPOSE: The purpose of this study was to compare combined PET/MRI with PET/CT
and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis.
METHODS: Ten patients (4 men and 6 women; 56.1 +/- 9.6 years old) were
prospectively enrolled for evaluation of suspected cardiac sarcoidosis or
myocarditis. Written informed consent was obtained. Following administration of
9.9 +/- 0.9 mCi F-FDG, patients underwent standard cardiac PET/CT followed by
combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included
ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging.
Myocardial involvement was assessed with separate analysis of combined PET/MRI,
PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates
of radiation dose were derived from the applied doses of F-FDG and CT protocol
parameters. RESULTS: Imaging was acquired with a delay from F-FDG injection of
90.2 +/- 27.4 minutes for PET/CT and 207.7 +/- 40.3 minutes for PET/MRI. Total
scan time for PET/MRI was significantly longer than for PET/CT (81.4 +/- 14.8 vs
12.0 minutes, P < 0.001). Total effective radiation dose was significantly lower
for PET/MRI compared with PET/CT (6.9 +/- 0.6 vs 8.2 +/- 1.1 mSv, P = 0.007).
There was no significant difference in the number of positive cases identified
between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI
(n = 8 [80%]), P = 0.091. CONCLUSIONS: Simultaneous cardiac PET/MRI is feasible
in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic
image quality.
PMID- 28418950
TI - Sacral Fatigue Fracture in a Military Recruit.
AB - A 19-year-old male military recruit presented with 3 weeks of persistent left hip
and groin pain after abnormally twisting his hip during a hike. Initial
radiographs were interpreted as negative. He subsequently underwent a bone scan
which revealed linear left sacral uptake along or paralleling the sacroiliac
joint. Differential diagnostic considerations included unilateral sacroiliitis
and sacral fracture. SPECT/CT was performed which confirmed left sacral fatigue
stress fracture. Transitional lumbosacral anatomy was evident on radiographs with
pseudoarticulation of the transitional left S1 transverse process with the
sacrum. We postulate this predisposed the recruit to sacral fracture.
PMID- 28418951
TI - Putaminal Hypometabolism Exceeding Caudate Abnormalities on 18F-FDG PET in
Huntington Disease.
AB - An F-FDG PET scan performed on a patient suspected of having early Huntington
disease (HD) showed marked hypometabolism in bilateral putamen that was
significantly worse than the hypometabolism in caudate. While HD could not be
completely excluded, the scan finding was felt to be somewhat atypical for HD
because of a lesser degree of caudate involvement. Genetic testing eventually
confirmed the diagnosis of HD. This case shows that diagnosis of HD should still
be considered even when putaminal hypometabolism exceeds caudate? changes on F
FDG PET imaging.
PMID- 28418952
TI - FDG PET/CT Findings of Nodular Sclerosis-Subtype Classic Hodgkin Lymphoma
Presented as Mediastinal Nodal Lesions at Onset But as Predominant Osseous
Disease at Relapse.
AB - Nodular sclerosis-subtype classic Hodgkin lymphoma in general manifests as bulky
mediastinal lymphadenopathy but very rarely involves bones. We report FDG PET/CT
findings of a 19-year-old man with pathology-proven, nodular sclerosis-type
classic Hodgkin lymphoma. His initial FDG PET/CT scan at the diagnosis showed
only hypermetabolic lymphadenopathy in the mediastinum. However, the FDG PET/CT
acquired when the disease recurred 20 months later showed predominant osseous
disease without additional nodal lesions outside the mediastinum.
PMID- 28418953
TI - Pulmonary Perfusion Scan Mimicking Hepatobiliary Scintigraphy in a Patient With
an Uncommon Manifestation of Granulomatosis With Polyangiitis.
AB - A 36-year-old man with known granulomatosis with polyangiitis underwent
quantitative ventilation-perfusion pulmonary scintigraphy as part of an initial
evaluation for lung transplant candidacy. Radiotracer uptake on the perfusion
study has the appearance of the hepatic silhouette, drawing initial concern that
there may have been a misadministration of Tc with a hepatobiliary agent.
Comparison CT reveals extensive cystic bronchiectasis, parenchymal destruction,
and volume loss involving the entire left lung and basal portions of the right
lung, with the residual portions of functional lung parenchyma conforming to a
shape similar to the liver.
PMID- 28418954
TI - Aortic Root Abscess Clearly Shown on 111In-Leukocyte Scan But Less Obvious on
Transesophageal Echocardiogram.
AB - A 79-year-old man with history of aortic stenosis, status post bioprosthetic
aortic valve replacement, episodes of bacteremia, and endocarditis presented to
hospital with fever. Clinical assessment led to suspicion of possible
endocarditis. Initial interpretation of transesophageal echocardiogram was
inconclusive without vegetation in mitral/aortic valve. An In-leukocyte scan
demonstrated increased uptake in the area of aortic valve, suggestive of
infection. Further review of the transesophageal echocardiogram showed signs of
annular abscess. This case highlights that combination of echocardiography with
white blood cell imaging increases the sensitivity to detect
endocarditis/perivalvular abscess.
PMID- 28418955
TI - Late 124I PET/CT Uptake Measurement-Assessment of Appropriate Examination
Protocol in Benign Thyroid Diseases.
AB - PURPOSE: This study aimed at investigating the performance of late I PET/CT for
radioiodine uptake (RAIU) measurement at 336 hours after administration in
patients with benign thyroid diseases requiring radioiodine therapy. Special
attention was paid to the comparability of I uptake (I-RAIU) to the clinical
standard (I-RAIU, probe measurement). Considering cost aspects, we sought to
establish an economically reasonable examination protocol based on scan duration
and administered activity. METHODS: List-mode PET data sets of 40-minute
acquisition time were acquired 336 hours after administration of 1 MBq I in 18
patients. Different scan durations were simulated by different reconstruction
intervals (RIs) ranging from 5 seconds to 40 minutes, and total thyroid activity
was measured. Mean I-RAIU levels of each RI were compared with mean I-RAIU levels
(3 MBq). A hypothetical scan duration or hypothetical activity, respectively, was
sought by means of a proportion equation, considering that the length of an RI is
equitable to a hypothetical activity. RESULTS: After 336 hours, the mean total
thyroid activity was 254 +/- 7.7 kBq for I and 26.9 +/- 8.7 kBq for I. The mean I
RAIU and I-RAIU showed high levels of agreement for RI from 2 minutes to 40
minutes. Reconstruction interval shorter than 2 minutes did not result in
sufficient agreement. CONCLUSIONS: The present study confirmed the feasibility of
late I PET/CT as alternative method for RAIU measurement in patients with benign
thyroid diseases; 1 MBq I PET/CT scans as short as 2 minutes resulted in RAIU
levels comparable to those of standard I-RAIU. The parameter "appropriate scan
duration activity product" is proposed to enable an economically reasonable
examination protocol.
PMID- 28418957
TI - Withholding, Withdrawing or Not Analyzing Data: Can Researchers Allow Data to be
Silent?
PMID- 28418958
TI - To Improve Cancer Treatment, We Need to Have Patients and Care Teams Connected!
PMID- 28418966
TI - Clinical Effectiveness and Safety of Intraoperative Methadone in Patients
Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded,
Controlled Trial.
AB - BACKGROUND: Patients undergoing spinal fusion surgery often experience severe
pain during the first three postoperative days. The aim of this parallel-group
randomized trial was to assess the effect of the long-duration opioid methadone
on postoperative analgesic requirements, pain scores, and patient satisfaction
after complex spine surgery. METHODS: One hundred twenty patients were randomized
to receive either methadone 0.2 mg/kg at the start of surgery or hydromorphone 2
mg at surgical closure. Anesthetic care was standardized, and clinicians were
blinded to group assignment. The primary outcome was intravenous hydromorphone
consumption on postoperative day 1. Pain scores and satisfaction with pain
management were measured at postanesthesia care unit admission, 1 and 2 h
postadmission, and on the mornings and afternoons of postoperative days 1 to 3.
RESULTS: One hundred fifteen patients were included in the analysis. Median
hydromorphone use was reduced in the methadone group not only on postoperative
day 1 (4.56 vs. 9.90 mg) but also on postoperative days 2 (0.60 vs. 3.15 mg) and
3 (0 vs. 0.4 mg; all P< 0.001). Pain scores at rest, with movement, and with
coughing were less in the methadone group at 21 of 27 assessments (all P = 0.001
to < 0.0001). Overall satisfaction with pain management was higher in the
methadone group than in the hydromorphone group until the morning of
postoperative day 3 (all P = 0.001 to < 0.0001). CONCLUSIONS: Intraoperative
methadone administration reduced postoperative opioid requirements, decreased
pain scores, and improved patient satisfaction with pain management.
PMID- 28418971
TI - Preanesthetic Assessment Clinic: Early Beginnings in the Bronx.
PMID- 28418972
TI - In Reply.
PMID- 28418973
TI - Rapid Fluid Infusion and Depth of Anesthesia.
PMID- 28418974
TI - In Reply.
PMID- 28418975
TI - Front of Neck Airway: The Importance of the Correct (Obese) Models and (Trained)
Participants in Study Design.
PMID- 28418976
TI - In Reply.
PMID- 28418977
TI - You Have a Plan B. Should You Have a Plan C?
PMID- 28418978
TI - In Reply.
PMID- 28418979
TI - Percutaneous Aponeurotomy and Lipofilling (PALF) versus Limited Fasciectomy in
Patients with Primary Dupuytren's Contracture: A Prospective, Randomized,
Controlled Trial.
PMID- 28418980
TI - Hemodynamic Study of Three Patterns of Flaps on Rats with a Novel Panoramic
Photographing Technique Involved.
PMID- 28418981
TI - Reply: Percutaneous Aponeurotomy and Lipofilling (PALF) versus Limited
Fasciectomy in Patients with Primary Dupuytren's Contracture: A Prospective,
Randomized, Controlled Trial.
PMID- 28418982
TI - Reply: Effectiveness of Autologous Fat Grafting in Adherent Scars: Results
Obtained by a Comprehensive Scar Evaluation Protocol.
PMID- 28418983
TI - Effectiveness of Autologous Fat Grafting in Adherent Scars: Results Obtained by a
Comprehensive Scar Evaluation Protocol.
PMID- 28418984
TI - Short article: Anger and quality of life in patients co-infected with HIV and
hepatitis C virus: a cross-sectional study (ANRS CO13-HEPAVIH).
AB - OBJECTIVE: The aim of this study is to document the relationship between anger
dimensions (state, trait, expression, and control) and quality of life (QoL) in
patients co-infected with HIV and hepatitis C virus (HCV). PATIENTS AND METHODS:
This is a cross-sectional study nested in the ANRS CO13-HEPAVIH French national
cohort. Anger and QoL were assessed using self-administered questionnaires in 536
HIV-HCV-co-infected patients. Correlations between anger scores (STAXI-2 scale)
and QoL scores (WHOQOL-HIV BREF scale) were assessed using Spearman's
coefficients. Multiple linear regression models were then used to test the
relationship between the different dimensions of anger and QoL after adjustment
for statistically significant psychosocial, sociobehavioral, and clinical
characteristics. RESULTS: Patients with excessive alcohol use or history of
injecting drug use had higher levels of anger. All dimensions of anger were
significantly correlated with impaired QoL for all six dimensions of the WHOQOL
HIV BREF scale. Greater internal experience of anger and impaired anger control
were confirmed as independent correlates of impaired QoL related to psychological
health, social relationships, and patients' beliefs after adjustment for
depressive symptoms, functional impact of fatigue, socioeconomic status, and HIV
related characteristics. CONCLUSION: Anger issues need close monitoring in HIV
HCV-co-infected patients, especially in patients with addictive behaviors.
Screening for problems in anger management and implementing individualized
psychotherapeutic strategies may help improve QoL in this population.
PMID- 28418985
TI - It's time to ponder.
PMID- 28418986
TI - Performance of Virological Testing for Early Infant Diagnosis: A Systematic
Review.
AB - BACKGROUND: Improved access to both maternal antiretroviral therapy and infant
prophylaxis may have an impact on the performance of virological assays for
diagnosis of HIV infection in infants. This systematic review was performed to
assess the diagnostic accuracy of virological testing at birth as well as the
performance of virological testing on dried blood spots at 6 weeks among HIV- and
antiretroviral (ARV)-exposed infants. METHODS: A systematic review was performed
for studies published between January 1, 2009 and January 30, 2015. The search
strategy included studies related to HIV, nucleic acid amplification tests, and
newborns/infants and queried PubMed, Embase, the Cochrane Library, LILACS as well
as several conference proceedings. Two independent reviewers collected studies
and extracted data. The final analysis includes summary estimates of the
sensitivities and specificities of the virological assays assessed. The GRADE
approach was used to assess the overall quality of evidence and Quality
Assessment of Diagnostic Accuracy Studies was used to evaluate the risk of bias
in the studies. RESULTS: A total of 2243 records were screened with a final
selection of 5 manuscripts. To assess the test characteristics of virological
testing at birth, 2 studies were used to calculate a pooled sensitivity of 69.3%
(95% confidence interval: 61.1 to 77.4) and a specificity of 99.9% (98.6-100%).
The quality of evidence to support the sensitivity of assays at birth was low,
whereas the quality of evidence for the specificity of such tests was
intermediate-high. In terms of the performance of virological testing on dried
blood spots for HIV- and ARV-exposed infants, 3 studies were used to calculate a
pooled sensitivity of 99.4% (98.3-100.00%) and specificity of 99.6% (99.1
100.00%). The quality of evidence for both outcomes was low. CONCLUSION: The
performance of polymerase chain reaction at birth demonstrates low sensitivity
and high specificity, reflecting the difficulty of detecting intrapartum
infections at birth and transmission dynamics. In addition, there is no evidence
to suggest poor performance of virological testing on dried blood spots for ARV
exposed infants. Overall, given the very limited and low-quality evidence,
further research is needed to assess the accuracy of polymerase chain reaction at
different time points and in the context of more effective prevention of mother
to-child transmission interventions.
PMID- 28418987
TI - The Roles of Behavioral and Social Science Research in the Fight Against
HIV/AIDS: A Functional Framework.
AB - Landmark advances have been made in HIV/AIDS prevention and treatment. These
include proof-of-concept and public health implementation of preexposure
prophylaxis and "treatment as prevention" to reduce HIV transmission as well as
definitive evidence of the clinical gain from early antiretroviral treatment
initiation. Significant progress has been made in understanding and addressing
the social contexts and behavioral factors that impact HIV prevention, care, and
treatment interventions. These include facilitating uptake of testing and
counseling, developing technology-based interventions that increase viral
suppression, reducing HIV/AIDS-related stigma, and addressing other
sociobehavioral and structural barriers to care and treatment. This evolving
landscape provides an important juncture to assess current and future directions
for HIV/AIDS behavioral and social science research (BSSR). We propose a
functional framework for HIV/AIDS-related BSSR, highlighting 4 primary BSSR
domains: (1) understanding vulnerable populations and contexts of risk ("Basic
BSSR"); (2) improving behavioral and social factor approaches to risk reduction,
prevention, and care ("Elemental BSSR"); (3) strengthening the design and
outcomes of biomedically focused research in HIV/AIDS treatment and prevention
("Supportive BSSR"); and (4) contributing building blocks to integrated HIV/AIDS
prevention and treatment approaches ("Integrative BSSR"). These domains and their
resulting confluence at the highest level underscore how fundamental and
essential BSSR is to current and future efforts to prevent, treat, and cure
HIV/AIDS.
PMID- 28418988
TI - HIV-Specific CD8 T Cells Producing CCL-4 Are Associated With Worse Immune
Reconstitution During Chronic Infection.
AB - BACKGROUND: Immunological nonresponse represents the Achilles heel in the
combination antiretroviral therapy (cART) effectiveness, and increases risk of
clinical events and death. CD8 T cells play a crucial role in controlling HIV
replication, and polyfunctional HIV-specific CD8 T cells have been associated
with nonprogressive HIV infection. However, the possible role of polyfunctional
CD8 T cells in predicting posttreatment immune reconstitution has not yet been
explored. The aim of this study was to identify functional markers predictive of
immunological response to cART in chronic HIV-infected patients. METHODS: A
cohort of chronic HIV-infected individuals naive to cART were enrolled in the
ALPHA study. CD4/CD8 T-cell subsets, their differentiation/activation, as well as
susceptibility to apoptosis were analyzed before and after 12 months of cART.
Moreover, CD8 T cells polyfunctional response after HIV antigenic stimulation was
also assessed. RESULTS: Results showed a significant correlation between worse
CD4 T-cell restoration and low frequency of naive CD4 T cells, high frequency of
effector memory CD4 T cells, and high susceptibility to apoptosis of CD4 T cells
all before cART. Moreover, CD8 functional subsets expressing total C-C motif
chemokine ligand 4 (CCL-4) or in combination with CD107a and interferon gamma
(IFNgamma) were negatively associated with immune reconstitution. CONCLUSIONS: In
conclusion, our study shows that a more differentiated phenotype of CD4 T cells
and CCL-4-producing CD8 T cells could represent valuable predictors of worse
immune reconstitution. These parameters may be used as tools for identifying
patients at risk of immunological failure during cART and eventually represent
the basis for innovative therapeutic strategies.
PMID- 28418989
TI - Impact of Antiretroviral Treatment Containing Tenofovir Difumarate on the
Telomere Length of Aviremic HIV-Infected Patients.
AB - OBJECTIVE: To evaluate the in vivo relevance of the inhibitory effect of
tenofovir on telomerase activity observed in vitro. DESIGN: Cross-sectional study
of HIV-infected patients with suppressed virological replication (HIV RNA <50
copies/mL for more than 1 year). METHODS: Telomere length in whole blood was
measured by quantitative real-time polymerase chain reaction. We performed a
multivariate analysis to elucidate variables associated with telomere length and
also evaluated the association between telomere length and use of tenofovir
difumarate (TDF) adjusted by significant confounders. RESULTS: 200 patients
included, 72% men, median age 49 (IQR 45-54.5), 103 with exposure to a TDF
containing antiretroviral treatment (ART) regimen (69.9% for more than 5 years)
and 97 never exposed to a TDF containing ART regimen. In the multivariate
analysis, significant predictors of shorter telomere length were older age (P =
0.008), parental age at birth (P = 0.038), white race (P = 0.048), and longer
time of known HIV infection (10-20 and >=20 years compared with <10 years, P =
0.003 and P = 0.056, respectively). There was no association between TDF exposure
and telomere length after adjusting for possible confounding factors (age,
parental age at birth, race, and time of HIV infection). Total time receiving ART
and duration of treatment with nucleoside reverse transcriptase inhibitors were
associated with shorter telomere length, but these associations were explained by
time of known HIV infection. CONCLUSIONS: Our data do not suggest that telomerase
activity inhibition caused by TDF in vitro leads to telomere shortening in
peripheral blood of HIV-infected patients.
PMID- 28418990
TI - Bone Density, Microarchitecture, and Tissue Quality After Long-Term Treatment
With Tenofovir/Emtricitabine or Abacavir/Lamivudine.
AB - OBJECTIVES: HIV infection has been associated with reduced bone mineral density
(BMD). Antiretroviral therapy (ART) has a deleterious effect on BMD, but its
effect on bone fragility is not clear. The objective of this study is to analyze
the BMD, microarchitecture, and tissue quality of bone in patients receiving long
term tenofovir- or abacavir-based ART. DESIGN: We conducted a cross-sectional
study in patients with HIV undergoing tenofovir or abacavir ART for more than 5
years. METHODS: We measured BMD using dual X-ray absorptiometry ,bone
michroarchitecture using trabecular bone score (TBS), and bone tissue quality
using microindentation. TBS is a dual X-ray absorptiometry-based software that is
more highly correlated with bone fragility than BMD. Microindentation (BMSi)
directly assesses bone quality at the tissue level. RESULTS: A total of 63
patients were included in this study, with 36 belonging to the TDF-FTC group and
27 to the ABC-3TC group. Patients receiving TDF-FTC treatment showed lower BMD
values than those in the ABC-3TC group. We found no differences in TBS or
microindentation between the 2 groups. However, after adjusting for sex, age,
body mass index, and 25[OH]vitD we found lower BMSi and thus poorer bone
properties in the TDF-FTC group than in the ABC-3TC group [beta coefficient
3.594 (confidence interval: 95% -0.12 to -7.61); P = 0.043]. CONCLUSIONS: Long
term treatment with TDF-FTC leads to impaired bone health, not only in terms of
BMD but also in terms of bone quality, another determinant of overall bone
strength. To complement BMD-based predictions, these other techniques may also be
used to identify patients with excess fracture risk.
PMID- 28418991
TI - Effect of Legal Status on the Early Treatment Outcomes of Migrants Beginning
Combined Antiretroviral Therapy at an Outpatient Clinic in Milan, Italy.
AB - OBJECTIVE: In a setting of free access to HIV care, we compared the early
treatment outcomes of HIV-infected undocumented migrants (UMs), documented
migrants (DMs), and Italian subjects. METHODS: The clinical data of 640 Italians
and 245 migrants who started combined antiretroviral therapy (cART) at an HIV
clinic in Milan, Italy, were reviewed. The migrants were mainly Latin Americans
(83 DMs and 56 UMs) or sub-Saharan Africans (52 DMs and 11 UMs), but a minority
were of other origin (33 DMs and 10 UMs). Retention in follow-up and HIV
suppression were compared between UMs, DMs, and natives 12 months +/- 90 days
after start of cART. RESULTS: There were no significant between-group differences
in the stage of HIV infection at the start of cART or the type of regimen
received. The Latin American DMs and UMs included a higher proportion of
transgender women than the other ethnic groups (P < 0.001). The UMs were less
frequently followed up after 12 months than the DMs and natives (P = 0.004) and
were more frequently permanently lost to follow-up (P < 0.001). UM status was an
independent predictor of lost to follow-up (adjusted odds ratio 8.05, P < 0.001).
The DMs and UMs were less frequently HIV suppressed after 12 months than the
natives (78% and 80.7% vs 90.5%, P = 0.001), and Latin American migrants were
significantly less likely to be virologically suppressed than the natives
(adjusted odds ratio 0.30, P = 0.001). CONCLUSIONS: Despite their free access to
cART, subgroups of migrants facing multiple levels of vulnerability still have
difficulties in gaining optimal HIV care.
PMID- 28418992
TI - Initiation of Antiretroviral Therapy Containing Integrase Inhibitors Increases
the Risk of IRIS Requiring Hospitalization.
PMID- 28418993
TI - Solid Papillary Breast Carcinomas Resembling the Tall Cell Variant of Papillary
Thyroid Neoplasms: A Unique Invasive Tumor With Indolent Behavior.
AB - Thirteen cases of invasive solid papillary breast carcinomas resembling the tall
cell variant of papillary thyroid neoplasms (BPTC) are reported here. Some cases
had long-term follow-up. BPTC is a special type of primary breast neoplasm
showing a triple-negative profile but low aggressive potential. Knowledge on BPTC
is still scanty; therefore, the aim of the present paper was to report on the
features of an additional 13 cases. All the patients were female individuals, and
the mean age at presentation was 62.6 years; nodule sizes ranged from 0.6 to 2.5
cm (average, 1.6 cm). All the cases were characterized on histology by papillary,
follicular as well as solid structures. The cells were columnar, eosinophilic
mostly with granular cytoplasms, rich in mitochondria, with the features of
oncocytes in no fewer than 7 cases. Estrogen and progesterone receptors as well
as HER2 were consistently negative. The Ki67 proliferative index was low. Markers
consistent with thyroid origin, such as TTF1 and thyroglobulin, were negative.
Five cases stained for mammoglobin and GATA 3 were positive. All cases proved to
be invasive and 2 cases each experienced metastases to 1 lymph node (axillary and
intramammary). One case of the latter had a local recurrence. Nevertheless, all
the patients are alive, free of disease 24 to 132 months after surgery, of which
8 are without further treatment The present series confirms that BPTC is a
primary breast tumor of low malignant potential.
PMID- 28418994
TI - Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and
Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma.
AB - Microcystic, elongated, and fragmented (MELF) pattern is seen in the invasive
front of some endometrial endometrioid carcinomas. Although MELF pattern can be
expected as an indicator of patient outcomes, its prognostic significance remains
unclear. This study was conducted to elucidate clinicopathologic features and the
prognostic impact of MELF pattern in patients with endometrial endometrioid
carcinoma. We retrospectively analyzed data of 479 consecutive patients with
endometrial endometrioid carcinoma that had been surgically resected. In 45 of
427 patients (11%) with low-grade endometrioid carcinoma, MELF pattern was found,
but it was found in none of the 52 patients with high-grade endometrioid
carcinoma. Among the patients with low-grade endometrioid carcinoma, MELF pattern
was associated significantly with larger tumor size, myometrial invasion of more
than 50%, advanced International Federation of Gynecology and Obstetrics stages,
lymphovascular space invasion, lymph node metastasis, papillary architecture, and
mucinous differentiation. However, survival analysis revealed that the patients
with MELF pattern showed no significantly worse prognosis than those without MELF
pattern either in disease-specific survival or in recurrence-free survival. MELF
was not a significant prognosticator after adjustment for International
Federation of Gynecology and Obstetrics stage (disease-specific survival [hazard
ratio, 1.47; 95% confidence interval, 0.28-7.67; P=0.64], recurrence-free
survival [hazard ratio, 0.98, 95% confidence interval, 0.32-2.99, P=0.98]).
Immunohistochemical analysis revealed that MELF pattern was positive for p16 and
p21 and almost negative for Ki-67 labeling, which suggested that tumor cells in
MELF pattern were involved in growth arrest or cellular senescence. We conclude
that MELF pattern could have little impact on outcomes of patients with low-grade
endometrial endometrioid carcinoma.
PMID- 28418995
TI - Kidney Biopsy Yield: An Examination of Influencing Factors.
AB - Kidney biopsies are conducted under varying scenarios, presenting variables that
could potentially influence yield and adequacy of tissue collected. We
retrospectively reviewed 636 native and allograft kidney biopsies, and compared
tissue collected between differing practitioners performing the biopsy
(nephrologists or radiologists), imaging modalities for guidance (ultrasound or
computed tomography), gauge needle used (18 or 16 G), and between on-site
evaluators of biopsy adequacy conducted at the time of biopsy (general
pathologists, renal pathologists, nephrologists). For radiologists using
ultrasound guidance and 18 G needles, those using on-site evaluation of adequacy
collected more glomeruli and glomeruli per length of tissue core than those not
using on-site evaluation. Radiologists not using on-site evaluation but who used
a larger bore needle (16 vs. 18 G) could generally collect comparable tissue as
other biopsy performers who used on-site evaluation. Radiologists performing
ultrasound-guided biopsies with 18 G needles without on-site evaluation
consistently provided poorer tissue yield and had a higher rate of providing
insufficient tissue so that a diagnosis could not be rendered. Nephrologists
collected less total length of tissue cores, glomeruli, and arteries per case
(whether performing the biopsy and/or performing on-site adequacy) compared with
other groups using on-site evaluation, however, providing comparable density of
glomeruli and arteries. Complication rates did not differ between compared groups
using 18 G needles. It is our observation that the various conditions by which a
kidney biopsy is obtained influences the yield of tissue collected and the
subsequent ability for a pathologist to effectively provide a diagnosis.
PMID- 28418996
TI - Mobilizing Immune Cells With Exercise for Cancer Immunotherapy.
AB - Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy
are effective in treating blood cancers and posttransplant infections, but low
circulating cell numbers in patients and donors are oftentimes a limiting factor.
We postulate that a single exercise bout will increase the yield of patient- and
donor-derived HSCs and cytotoxic lymphocytes to improve this form of treatment
for cancer patients.
PMID- 28418997
TI - Exercise Is Medicine, But Does It Interfere With Medicine?
AB - Exercise frequently is prescribed therapeutically, either on its own or combined
with drugs. A drug's absorption, distribution, metabolism, and excretion can be
affected by the user's anatomy and physiology, which are both changed by the
myriad of complex adaptations to acute and chronic exercise. This article reviews
the research that suggests exercise may influence a drug's plasma concentration,
and thus its efficacy and safety.
PMID- 28418999
TI - Interval Walking Training Can Increase Physical Fitness in Middle-Aged and Older
People.
AB - No long-term exercise training regimen with high adherence and effectiveness for
middle-aged and older individuals is currently broadly available in the field. To
address this problem, we developed an exercise training system comprising
interval walking training and an information technology network that requires
only minimal staff support. We hypothesized that our training system could
increase physical fitness in older people.
PMID- 28418998
TI - Physical Activity as Cause and Cure of Muscular Pain: Evidence of Underlying
Mechanisms.
AB - Work-related physical activity (PA), in terms of peak loads and sustained and/or
repetitive contractions, presents risk factors for the development of muscular
pain and disorders. However, PA as a training tailored to the employee's work
exposure, health, and physical capacity offers prevention and rehabilitation. We
suggest the concept of "Intelligent Physical Exercise Training" relying on
evidence-based sports science training principles.
PMID- 28419001
TI - New Insights Into the Impact of Dehydration on Blood Flow and Metabolism During
Exercise.
AB - Exercise-induced dehydration can lead to impaired perfusion to multiple regional
tissues and organs. We propose that the impact of dehydration on regional blood
flow and metabolism is dependent on the extent of the cardiovascular demand
imposed by exercise, with the greatest physiological strain seen when approaching
cardiovascular and aerobic capacities.
PMID- 28419000
TI - Exercise-Induced Autophagy in Fatty Liver Disease.
AB - Hepatic steatosis prevails each year. Autophagy is integral in mitochondrial
quality control and lipid homeostasis in the liver. No pharmacological strategies
are currently available to reduce hepatic steatosis, but exercise has been known
to improve clinical outcomes of chronic liver disease, particularly nonalcoholic
fatty liver disease (NAFLD). Recent studies suggest that exercise may improve
NAFLD through enhancing autophagy.
PMID- 28419002
TI - Skeletal Muscle Remodeling: Interconnections Between Stem Cells and Protein
Turnover.
AB - Nutrition and exercise are important components of a healthy lifestyle to improve
rates of hypertrophic and nonhypertrophic skeletal muscle remodeling. We provide
evidence to support the hypothesis that muscle stem cells and protein turnover
are collaborative, not separate, mechanisms supporting muscle remodeling by
facilitating protein, nuclear, and cellular turnover in response to the ingestion
of protein dense foods and exercise.
PMID- 28419004
TI - Small Sample Sizes Confound Understanding of Cardiometabolic Responses to
Exercise.
AB - Considerable variability exists in the cardiometabolic disease biomarker response
to exercise. We propose that a major contributor to this heterogeneity is
underpowered studies due to small sample sizes. To test our hypothesis, we
conducted a systematic review to identify meta-analyses/reviews of randomized
controlled trials (RCT) and RCT that examined the cardiometabolic disease
biomarker response to aerobic and resistance exercise.
PMID- 28419005
TI - Clinical Utility of Polymerase Chain Reaction Testing for Streptococcus
pneumoniae in Pediatric Cerebrospinal Fluid Samples: A Diagnostic Accuracy Study
of More Than 2000 Samples From 2004 to 2015.
AB - The aim of this retrospective study was to review the diagnostic accuracy of real
time polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) samples
for Streptococcus pneumoniae DNA in comparison with traditional bacterial
culture. The hypothesis was that PCR is more sensitive than culture and would
detect more cases of pneumococcal meningitis, particularly in children treated
with antimicrobials before CSF sampling occurred. Patients younger than 16 years
of age who had a CSF sample tested for S. pneumoniae DNA by PCR between 2004 and
2015 were included. A total of 2025 samples were included, and the PCR had a
sensitivity of 100% and specificity of 98% for the detection of S. pneumoniae DNA
in comparison with culture. Of the 28 culture negative/PCR positive cases, 25
(89%) were probable meningitis cases and only 3 (11%) were suspected false
positive results. Nineteen (76%) of the 25 probable cases required ICU admission,
and 3 died (12%). Six different serotypes were found in the culture positive
patients (18C, 6B, 14, 22F, 7F and 33F). This study demonstrates that PCR testing
of CSF samples for S. pneumoniae is sensitive and specific when compared with
culture. PCR is particularly useful in detecting those cases where culture is
negative, perhaps relating to pre-CSF sampling administration of antimicrobials.
PMID- 28419006
TI - Plasma Interferon-Gamma-Inducible Protein 10 Level Associates With Abnormal
Memory B Cells Phenotypes in Perinatal HIV Infection.
AB - We demonstrate for perinatally HIV-infected children and adolescents receiving
combined antiretroviral therapy and in good clinical status with respect to HIV
disease that high concentrations of interferon-gamma-inducible protein 10
associate with increased exhausted memory B cells.
PMID- 28419008
TI - Protection Is Key in a Risky Business.
PMID- 28419007
TI - Persistence of Hepatitis B Immunity Following 3-dose Infant Primary Series in HIV
infected Thai Adolescents and Immunologic Response to Revaccination.
AB - BACKGROUND: HIV infection may alter immunologic response and the establishment of
immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to
determine the need to revaccinate perinatally HIV-infected Thai adolescents.
METHODS: Cross-sectional serologic tests for HBV, including hepatitis B surface
antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core
antibody (anti-HBc), were performed in perinatally HIV-infected adolescents.
Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune
reconstitution from highly active antiretroviral therapy (HAART) were
revaccinated using regular (10 MUg) 3-dose schedule given intramuscularly at 0-,
2- and 6-month intervals. RESULTS: Of 193 adolescents who received 3-dose infant
HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile
range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc
(indicating breakthrough infection), of which 4 (2%) had positive hepatitis B
surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents
had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated
adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs
seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and
97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects
responded to the first dose with anti-HBs antibody >=100 mIU/mL had a shorter
median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months;
P = 0.049). CONCLUSIONS: Only half of perinatally HIV-infected adolescents were
able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination
with 3-dose schedule is required in perinatally HIV-infected adolescents who did
not initiate HAART at the time of infant vaccination.
PMID- 28419009
TI - Working Together to Educate and Safeguard You.
PMID- 28419010
TI - Extending Short Peripheral Catheter Dwell Time: A Best Practice Discussion.
AB - Complications involving short peripheral catheters (SPCs) can significantly
affect health care costs, patient quality of life, morbidity, mortality, and
treatment expense, especially when the hospital stay is lengthened. This article
examines the relationship between SPC dwell time and the incidence of phlebitis
and potential bacteremia. The literature is replete with most studies supporting
SPCs remaining in situ until a clinical reason warrants catheter removal.
Removing and not routinely restarting unneccessary intravenous catheters can help
prevent catheter-related infections and other vascular complications and reduce
cost.
PMID- 28419011
TI - Establishing a Dedicated Difficult Vascular Access Team in the Emergency
Department: A Needs Assessment.
AB - Peripheral vascular access is one of the most common procedures performed in
emergency departments across the United States. Successful venipuncture is
critical in providing timely diagnosis and treatments for patients. The aim of
this article is to describe a needs assessment performed in a level-one academic
emergency department to establish the need for a dedicated team for patients with
difficult vascular access. Results from this assessment suggest that difficult
vascular access represents tangible threats to patient safety and increased use
of resources.
PMID- 28419012
TI - A Novel Needle-Free Blood Draw Device for Sample Collection From Short Peripheral
Catheters.
AB - A new US Food and Drug Administration-cleared needleless blood collection device
(PIVO; Velano Vascular, San Francisco, CA) for short peripheral catheters was
compared with conventional venipuncture for collecting blood samples for routine
laboratory analysis from adult healthy volunteers. The PIVO device was comparable
with venipuncture in terms of providing high-integrity samples (no hemolysis or
clotting), equivalent laboratory values, and better patient experience as
assessed by pain scores. Further studies to assess the overall utility of the
PIVO device are warranted.
PMID- 28419013
TI - Standardizing Best Nursing Practice for Implanted Ports: Applying Evidence-based
Professional Guidelines to Prevent Central Line-Associated Bloodstream
Infections.
AB - Nearly 3 million central vascular access devices (CVADs) are used in the United
States each year. These devices are an important advance in health care and
essential to oncology patients. However, CVADs are the most frequent cause of
central line-associated bloodstream infections (CLABSIs). CLABSI can be prevented
when evidence-based practices are followed consistently over time. Professional
organizations establish valid standards and guidelines to guide CVAD practice.
This article identifies strategies implemented at a comprehensive ambulatory
cancer center to integrate professional evidence-based standards and guidelines
for implanted port care into nursing practice at the point of care.
PMID- 28419014
TI - Impact of Ultrasound on Short Peripheral Intravenous Catheter Placement on Vein
Thrombosis Risk.
AB - Approximately 90% of hospitalized patients have a short peripheral intravenous
catheter (SPC) placed. Methods of inserting the catheter have evolved over time
and now include the use of ultrasound (US)-guided procedures for placement.
Little is known about the impact that US-guided procedures have on the vein. This
study compared the rate of venous thrombosis in patients with and without US
guided catheter placement. This prospective, single-blind, observational study
assessed for venous thrombosis in 153 veins from 135 patients. Veins were
evaluated by a research nurse blinded to the method of placement between 48 and
72 hours after the SPC was placed. The Fisher exact test showed a significant
difference between vessel compressibility and catheter insertion method (P =
.0012). The proportion of noncompressible veins was significantly greater when US
was used in comparison with freehand SPC insertion. The Mantel-Haenszel chi
square value of 10.34 (P = .0013) showed that US insertion technique is
associated with a higher likelihood of noncompressible veins. This pilot study
provides compelling evidence that the use of US to assist with catheter placement
is associated with a higher rate of noncompressible veins at day 2 or 3. Further
studies are needed with a larger sample to determine the generalizability of the
results from this pilot study.
PMID- 28419015
TI - An Unanticipated Complication of Atopic Dermatitis.
AB - An infant with a history of atopic dermatitis presented to the emergency
department on 5 occasions with flulike symptoms. Eventually, this child presented
with signs of infection and increased intracranial pressure: fever, bulging
anterior fontanel, and leukocytosis. A computed tomography scan identified a
large frontal lobe brain abscess. The abscess was surgically drained; culture was
positive for Staphylococcus aureus. The initial source of the infected brain
abscess was explored. Ultimately, it was thought to be secondary to impetiginized
atopic dermatitis, an unusual but serious consequence of a common skin condition.
PMID- 28419016
TI - An Evaluation of a New Debriefing Framework: REFLECT.
AB - BACKGROUND: Postresuscitation debriefing (PRD) is recommended by the American
Heart Association guidelines but is infrequently performed. Prior studies have
identified barriers for pediatric emergency medicine (PEM) fellows including lack
of a standardized curriculum. OBJECTIVE: Our objective was to create and assess
the feasibility of a time-limited, structured PRD framework entitled REFLECT:
Review the event, Encourage team participation, Focused feedback, Listen to each
other, Emphasize key points, Communicate clearly, and Transform the future.
METHODS: Each PEM fellow (n = 9) at a single center was a team leader of a pre
intervention and post-intervention videotaped, simulated resuscitation followed
by a facilitated team PRD. Our intervention was a 2-hour interactive, educational
workshop on debriefing and the use of the REFLECT debriefing aid. Videos of the
pre-intervention and post-intervention debriefings were blindly analyzed by video
reviewers to assess for the presence of debriefing characteristics contained in
the REFLECT debriefing aid. PEM fellow and team member assessments of the
debriefings were completed after each pre-intervention and post-intervention
simulation, and written evaluations by PEM fellows and team members were
analyzed. RESULTS: All 9 PEM fellows completed the study. There was an
improvement in the pre-intervention and post-intervention assessment of the
REFLECT debriefing characteristics as determined by fellow perception (63% to
83%, P < 0.01) and team member perception (63% to 82%, P < 0.001). All
debriefings lasted less than 5 minutes. There was no statistical difference
between pre-intervention and post-intervention debriefing time (P = 1.00).
CONCLUSIONS: REFLECT is a feasible debriefing aid designed to incorporate
evidence-based characteristics into a PRD.
PMID- 28419017
TI - The Evaluation of Trauma Care: The Comparison of 2 High-Level Pediatric Emergency
Departments in the United States and Turkey.
AB - OBJECTIVE: The purpose of the study is to compare the outcomes of pediatric
trauma patients with motor vehicle crashes (MVCs) and motor vehicle versus
pedestrian crashes (MPCs) at a level 1 pediatric trauma center in the United
States and a pediatric trauma center in Turkey. METHODS: The medical records of
all pediatric MVC and MPC subjects presenting to the emergency departments (EDs)
of a level 3 hospital in Turkey (Izmir Tepecik Training and Research Hospital
[ITTRH]) and a level 1 pediatric trauma center in the United States (Children's
Medical Center Dallas [CMCD]) over a 1-year period were reviewed. Data that were
collected include patient demographics, prehospital report (mechanism of injury,
mode of transportation), injury severity score (ISS), abbreviated injury scale
score, Glasgow Coma Scale score, ED length of stay, ED interventions, ED and
hospital disposition, and mortality. Patients with moderate (ISS, 5-15) and
severe (ISS, >15) trauma scores were included in the study. RESULTS: One hundred
six patient charts from the ITTRH and 125 patient charts from the CMCD with
moderate and severe ISS due to MVCs and MPCs were reviewed. Most of the patients
were pedestrians (86%) in the ITTRH group and passengers (60%) in the CMCD group.
The percentage of patients transferred by ambulance (ground or air) to the CMCD
and the ITTRH was 97.9% and 85%, respectively. Fifteen percent of ITTRH patients
and 2.1% of CMCD patients arrived by private vehicle. Emergency department
arrival ISS and Glasgow Coma Scale were similar between the 2 hospitals (P >
0.05). The overall mortality rate in the study population was 8.8% (11/125) at
the CMCD and 4.7% (5/106) at the ITTRH. (P = 0.223). Blood product utilization
was significantly higher in the CMCD group compared with the ITTRH group (P =
0.005). The use of hypertonic saline/mannitol/hyperventilation in patients with
significant head trauma and increased intracranial pressure was higher in the
ITTRH group (P = 0.000). CONCLUSIONS: This is the first study that compared
pediatric trauma care and outcome at a level 1 pediatric trauma center in the
United States and a pediatric hospital in Turkey. Our findings highlight the
opportunities to improve pediatric trauma care in Turkey. Specifically, there is
a need for national trauma registries, enhanced trauma education, and
standardized trauma patient care protocols. In addition, efforts should be
directed toward improving prehospital care through better integration within the
health care system and physician participation in educating prehospital
providers. Data and organized trauma care will be instrumental in system-wide
improvement and developing appropriate injury-prevention strategies.
PMID- 28419018
TI - Diagnosis of a Posterior Fracture Dislocation of the Medial Clavicle in an
Adolescent With Point-of-Care Ultrasound.
AB - We report a case of an adolescent patient with medial clavicular tenderness after
a fall on the lateral left shoulder. Initial radiographs did not reveal a
fracture or dislocation. Point-of-care ultrasound was used to diagnose a
posterior clavicular fracture dislocation.
PMID- 28419019
TI - Complexities of Consent: Ethics in the Pediatric Emergency Department.
AB - Informed consent is a communicative process of sharing information with patients,
which helps assure their understanding of the information provided and asks for
their permission to proceed. Informed consent allows a patient or a patient's
family to use his or her own value system to determine the need for a particular
procedure or test. Asking a patient for permission to treat requires the provider
to respect the patient's autonomy through allowing him or her to be an active
part of the decision-making process. Consent in the pediatric emergency
department can be a complex process. Parental consent is generally required for
medical evaluation and treatment of pediatric patients, but in the pediatric
emergency department, there are exceptions to this rule. If the provider
determines that a parent's refusal of consent places the child at risk of harm,
then consent is not necessary. By using the concepts of Emergency Medical
Treatment and Active Labor Act, in emergent situations, consent may not be
necessary. Finally, adolescents are often deeply concerned about privacy-their
acceptance of appropriate care is often based on this promise of confidentiality.
In the emergency department, adolescents can therefore be treated for issues
relating to reproductive care without parental consent. It is important for the
emergency department physician to understand the rules surrounding the care of
pediatric patients to avoid compromising their privacy and ultimately their well
being and medical care.
PMID- 28419020
TI - Education in the Waiting Room: Description of a Pediatric Emergency Department
Educational Initiative.
AB - OBJECTIVE: The aim of this study was to understand parents' awareness of and
reactions to a slide presentation based waiting-room educational initiative.
METHODS: This was a prospective observational study at a Canadian tertiary-care
pediatric emergency department (ED) with an annual census of 68,000 visits. An
anonymous parental survey was developed de novo, and parents were asked to
complete the survey during their low-acuity ED visit over a 2-week study period.
Descriptive statistics were used to describe responses and themes. RESULTS:
Parents completed 520 surveys (733 approached, 70.9% response rate). Eighty-three
percent of respondents had previously sought care in the ED. Most parents (68.9%)
were aware of the slide presentation, but only 33.7% were able to watch it in its
entirety (20 minutes' duration). Of those who watched the whole presentation,
62.9% understood that lower-acuity cases are assessed in the ambulatory zone of
the ED, and sicker children are assessed in the acute zone (89.4%), 79.9% felt
the presentation helped them to understand how the ambulatory zone functions, and
83.2% appreciated the current wait-time information. General questions about
common health concerns were answered correctly in 58.3% (fever), 56.0%
(gastroenteritis), 50.5% (abdominal pain/constipation), 35.7% (earache), and
17.0% (head injury). CONCLUSIONS: The majority of parents were aware of this
waiting-room educational initiative, but there was variable uptake of
information. Parents watching the entire presentation appreciated the information
provided, especially wait-time information, and felt it improved their
experience. Knowledge of common health conditions was low; novel methods of
knowledge transfer must be utilized and evaluated.
PMID- 28419021
TI - Clinical Toxicity of Acute Overdoses With L-Thyroxin in Children.
AB - OBJECTIVES: L-Thyroxine ingestion is rarely seen in children; here, we report our
experience of it. This study describes the clinical characteristics and
laboratory findings of acute L-thyroxine ingestion in children. METHODS: This
retrospective study enrolled patients treated for L-thyroxine ingestion at
Kayseri Teaching Hospital between September 2013 and September 2016. Clinical
characteristics and laboratory findings are described. Ethical approval was not
obtained because the study was retrospective. RESULTS: The incidence of L
thyroxine ingestion was 0.07% to 1.2% per year. There were 14 patients. Twelve
patients were asymptomatic, but 2 (14.2%) exhibited tachycardia and hypertension.
Thyroid hormone levels were elevated in 3 patients (21.4%). Eleven patients did
not require medical treatment (78.4%); 3 did. No serious complication or death
was observed. CONCLUSIONS: Acute ingestion has a benign course. Serious
complications are uncommon but may appear several hours or days after ingestion;
therefore, patients with L-thyroxine ingestion should be followed closely for 2
weeks.
PMID- 28419022
TI - Computed Tomography Angiographic Assessment of Acute Chest Pain.
AB - Acute chest pain is a leading cause of Emergency Department visits. Computed
tomography angiography plays a vital diagnostic role in such cases, but there are
several common challenges associated with the imaging of acute chest pain, which,
if unrecognized, can lead to an inconclusive or incorrect diagnosis. These
imaging challenges fall broadly into 3 categories: (1) image acquisition, (2)
image interpretation (including physiological and pathologic mimics), and (3)
result communication. The aims of this review are to describe and illustrate the
most common challenges in the imaging of acute chest pain and to provide
solutions that will facilitate accurate diagnosis of the causes of acute chest
pain in the emergency setting.
PMID- 28419023
TI - Interrelations of Epicardial Fat Volume, Left Ventricular T1-Relaxation Times and
Myocardial Strain in Hypertensive Patients: A Cardiac Magnetic Resonance Study.
AB - PURPOSE: This cardiac magnetic resonance study was performed to assess myocardial
fibrosis by evaluating T1-relaxation time (T1), to measure left ventricular (LV)
strain, and to determine epicardial fat volume (EFV) in hypertensive patients
with no history of cardiovascular (CV) events and to relate the results to the
presence of coronary atherosclerotic artery disease (CAD) in these patients.
MATERIALS AND METHODS: A total of 123 subjects were examined at 1.5 T. Of them,
98 were hypertensive patients (58 men; mean age, 62.9+/-10.7 y; body mass index,
29.0+/-5.6 kg/m) and 25 were controls without CV risk factors or disease (13 men;
60.1+/-10.7 y; 28.1+/-5.4 kg/m). All patients had a well-treated blood pressure.
In the hypertensive group, 56 patients had no CAD, whereas 42 patients had CAD.
T1 was assessed by a modified Look-Locker inversion recovery sequence.
Longitudinal and circumferential peak systolic strain (LS; CS) was determined
with dedicated cardiac magnetic resonance software (feature tracking). EFV
(normalized to the body surface area) was assessed by a 3D Dixon sequence.
RESULTS: T1 (ms) and EFV (mL/m) were higher and CS and LS (%) were lower in
hypertensive patients compared with those in nonhypertensive controls (P<0.05),
independent of the presence of CAD (controls: T1=967.2+/-16.9, LS=-25.2+/-4.6,
CS=-28.7+/-5.0, EFV=58.2+/-21.1; hypertensive patients overall: T1=991.3+/-45.5,
LS=-21.0+/-4.5, CS=-25.0+/-5.9, EFV=71.1+/-25.3; hypertensive patients without
CAD: T1=991.6+/-48.4, LS=-21.0+/-4.7, CS=-24.6+/-6.3, EFV=71.3+/-26.6;
hypertensive patients with CAD: T1=986.7+/-39.2, LS=-21.1+/-4.3, CS=-25.5+/-5.4,
EFV=70.9+/-23.6). There were no significant differences between hypertensive
patients with and those without CAD and between patients grouped according to the
number of vessels affected (0-vessel disease, 1-vessel disease, 2-vessel disease,
or 3-vessel disease). CONCLUSIONS: Hypertension is associated with signs of
myocardial fibrosis and an impaired LV contractility despite a normal LV ejection
fraction, as well as with an increased EFV. However, CAD, in the absence of
previous pathologies with consecutive myocardial ischemic damage, did not
additionally affect these parameters.
PMID- 28419024
TI - The Effects of Exercise Training on Anxiety in Fibromyalgia Patients: A Meta
analysis.
AB - : Physical inactivity and comorbid anxiety symptoms are prevalent among
fibromyalgia (FM) patients. Exercise training may be an effective alternative
therapy to reduce these symptoms. PURPOSE: This study aimed to evaluate the
effects of exercise training on anxiety symptoms in patients with FM and to
examine whether variables of theoretical or practical importance moderate the
estimated mean effect. METHODS: Twenty-five effects were derived from 10 articles
published before June 2016 located using Google Scholar, MEDLINE, PsycINFO,
PubMed, and Web of Science. Trials involved 595 patients with FM (mean age = 47.6
yr, 97.5% female) and included both randomization to exercise training (n = 297)
or a nonexercise control condition (n = 298) and an anxiety outcome measured at
baseline and during and/or after exercise training. Hedges' d effect sizes were
computed, data for moderator variables were extracted, and random effects models
were used to estimate sampling error and population variance for all analyses.
Meta-regression quantified the extent to which patient and trial characteristics
moderated the mean effect. RESULTS: Exercise training significantly reduced
anxiety symptoms by a mean effect Delta of 0.28 (95% confidence interval [CI] =
0.16-0.40). No significant heterogeneity was observed (Q24 = 30.79, P = 0.16, I =
25.29%). Program duration (beta = 1.44, z = 2.50, P <= 0.01) was significantly
related to the overall effect, with significantly larger anxiety improvements
resulting from programs lasting greater than 26 wk (Delta = 0.35, 95% CI = 0.05
0.66) compared with those lasting less than 26 wk (Delta = 0.26, 95% CI = 0.13
0.39). CONCLUSION: Exercise training improves anxiety symptoms among FM patients.
The findings also suggest that larger anxiety symptom reductions will be achieved
by focusing on longer exercise programs while promoting long-term adherence.
Future well-designed investigations are required to examine the potential
moderating effect of pain-related improvements in FM patients.
PMID- 28419025
TI - Ensemble Methods for Classification of Physical Activities from Wrist
Accelerometry.
AB - PURPOSE: To investigate whether the use of ensemble learning algorithms improve
physical activity recognition accuracy compared to the single classifier
algorithms, and to compare the classification accuracy achieved by three
conventional ensemble machine learning methods (bagging, boosting, random forest)
and a custom ensemble model comprising four algorithms commonly used for activity
recognition (binary decision tree, k nearest neighbor, support vector machine,
and neural network). METHODS: The study used three independent data sets that
included wrist-worn accelerometer data. For each data set, a four-step
classification framework consisting of data preprocessing, feature extraction,
normalization and feature selection, and classifier training and testing was
implemented. For the custom ensemble, decisions from the single classifiers were
aggregated using three decision fusion methods: weighted majority vote, naive
Bayes combination, and behavior knowledge space combination. Classifiers were
cross-validated using leave-one subject out cross-validation and compared on the
basis of average F1 scores. RESULTS: In all three data sets, ensemble learning
methods consistently outperformed the individual classifiers. Among the
conventional ensemble methods, random forest models provided consistently high
activity recognition; however, the custom ensemble model using weighted majority
voting demonstrated the highest classification accuracy in two of the three data
sets. CONCLUSIONS: Combining multiple individual classifiers using conventional
or custom ensemble learning methods can improve activity recognition accuracy
from wrist-worn accelerometer data.
PMID- 28419026
TI - The Gas Sampling Interval Effect on VO2peak Is Independent of Exercise Protocol.
AB - INTRODUCTION: There is a plethora of gas sampling intervals available during
cardiopulmonary exercise testing to measure peak oxygen consumption (VO2peak).
Different intervals can lead to altered VO2peak. Whether differences are affected
by the exercise protocol or subject sample is not clear. The purpose of this
investigation was to determine whether VO2peak differed because of the
manipulation of sampling intervals and whether differences were independent of
the protocol and subject sample. METHODS: The first subject sample (24 +/- 3 yr;
VO2peak via 15-breath moving averages: 56.2 +/- 6.8 mL.kg.min) completed the
Bruce and the self-paced VO2max protocols. The second subject sample (21.9 +/-
2.7 yr; VO2peak via 15-breath moving averages: 54.2 +/- 8.0 mL.kg.min) completed
the Bruce and the modified Astrand protocols. VO2peak was identified using five
sampling intervals: 15-s block averages, 30-s block averages, 15-breath block
averages, 15-breath moving averages, and 30-s block averages aligned to the end
of exercise. Differences in VO2peak between intervals were determined using
repeated-measures ANOVAs. The influence of subject sample on the sampling effect
was determined using independent t-tests. RESULTS: There was a significant main
effect of sampling interval on VO2peak (first sample Bruce and self-paced VO2max
P < 0.001; second sample Bruce and modified Astrand P < 0.05). The difference in
VO2peak between sampling intervals followed a similar pattern for each protocol
and subject sample, with 15-breath moving average presenting the highest VO2peak.
CONCLUSIONS: The effect of manipulating gas sampling intervals on VO2peak appears
to be protocol and sample independent. These findings highlight our
recommendation that the clinical and scientific community request and report the
sampling interval whenever metabolic data are presented. The standardization of
reporting would assist in the comparison of VO2peak.
PMID- 28419027
TI - Athletes Intending to Use Sports Supplements Are More Likely to Respond to a
Placebo.
AB - PURPOSE: We investigated associations between athletes' use of sport supplements
and their responsiveness to placebo and nocebo interventions. METHODS:
Participants (n = 627) reported their intention to use, and actual use of, sport
supplements. They then completed a 5 * 20 m repeat sprint protocol in the
baseline condition, before being randomized to one of three treatments.
Participants in the positive-belief treatment were administered an inert capsule
described as a potent supplement which would improve sprint performance.
Participants in the negative-belief treatment were administered an inert capsule
described as a potent supplement which would negatively affect sprint
performance. Participants in the control treatment received neither instruction
nor capsule. Twenty minutes after baseline trials, all participants completed the
same repeat sprint protocol in the experimental condition. RESULTS: Compared with
controls, no mean differences in performance were observed between baseline and
experimental conditions for the positive-belief treatment (-0.07% +/- 0.27%, d =
0.02), but mean differences were observed for the negative-belief treatment (
0.92% +/- 0.31%, d = 0.32), suggesting a moderate nocebo effect. In the positive
belief treatment, however, a relationship between intention to use supplements
and performance was observed. Performance worsened by -1.10% +/- 0.30% compared
with baseline for participants not intending to use supplements, worsened by
0.64% +/- 0.43% among those undecided about supplement use, but improved by 0.19%
+/- 0.24% among those participants intending to use supplements. CONCLUSIONS:
Information about a harmful supplement worsened repeat sprint performance (a mean
nocebo effect), whereas information about a beneficial supplement did not improve
performance (no mean placebo effect was observed). However, participants'
intention to use sport supplements influenced the direction and magnitude of
subsequent placebo responses, with participants intending to use supplements more
likely to respond to the positive intervention.
PMID- 28419028
TI - Physical Activity Assessment with the ActiGraph GT3X and Doubly Labeled Water.
AB - PURPOSE: To compare the degree to which four accelerometer metrics-total activity
counts per day (TAC per day), steps per day (steps per day), physical activity
energy expenditure (PAEE) (kcal.kg.d), and moderate- to vigorous-intensity
physical activity (MVPA) (min.d)-were correlated with PAEE measured by doubly
labeled water (DLW). Additionally, accelerometer metrics based on vertical axis
counts and triaxial counts were compared. METHODS: This analysis included 684
women and 611 men age 43 to 83 yr. Participants wore the Actigraph GT3X on the
hip for 7 d twice during the study and the average of the two measurements was
used. Each participant also completed one DLW measurement, with a subset having a
repeat. PAEE was estimated by subtracting resting metabolic rate and the thermic
effect of food from total daily energy expenditure estimated by DLW. Partial
Spearman correlations were used to estimate associations between PAEE and each
accelerometer metric. RESULTS: Correlations between the accelerometer metrics and
DLW-determined PAEE were higher for triaxial counts than vertical axis counts.
After adjusting for weight, age, accelerometer wear time, and fat free mass, the
correlation between TAC per day based on triaxial counts and DLW-determined PAEE
was 0.44 in women and 0.41 in men. Correlations for steps per day and
accelerometer-estimated PAEE with DLW-determined PAEE were similar. After
adjustment for within-person variation in DLW-determined PAEE, the correlations
for TAC per day increased to 0.61 and 0.49, respectively. Correlations between
MVPA and DLW-determined PAEE were lower, particularly for modified bouts of >=10
min. CONCLUSIONS: Accelerometer measures that represent total activity volume,
including TAC per day, steps per day, and PAEE, were more highly correlated with
DLW-determined PAEE than MVPA using traditional thresholds and should be
considered by researchers seeking to reduce accelerometer data to a single
metric.
PMID- 28419029
TI - Females with Unexplained Joint Pain Following Total Joint Arthroplasty Exhibit a
Higher Rate and Severity of Hypersensitivity to Implant Metals Compared with
Males: Implications of Sex-Based Bioreactivity Differences.
AB - BACKGROUND: Recent studies indicate that females demonstrate an increased risk of
experiencing adverse local tissue reactions, aseptic loosening, and revision
after primary metal-on-metal hip resurfacing arthroplasty compared with males;
the underlying biological mechanisms responsible for sex discrepancies in implant
failure remain unclear. In addition to anatomical and biomechanical sex
differences, there may be inherent immunological disparities that predispose
females to more aggressive adaptive immune reactivity to implant debris, i.e.,
metal sensitivity. METHODS: In this retrospective study, we analyzed sex
associated rates and levels of metal sensitization in 1,038 male and 1,575 female
subjects with idiopathic joint pain following total joint arthroplasty (TJA) who
were referred for in vitro metal-sensitivity testing. RESULTS: Females
demonstrated a significantly higher rate and severity of metal sensitization
compared with males. The median lymphocyte stimulation index (SI) among males was
2.8 (mean, 5.4; 95% confidence interval [CI], 4.9 to 6.0) compared with 3.5
(mean, 8.2; 95% CI, 7.4 to 9.0) among females (p < 0.05). Forty-nine percent of
females had an SI of >=4 (reactive) compared with 38% of males, and the implant
related level of pain was also significantly (p < 0.0001) higher among females
(mean, 6.8; 95% CI, 6.6 to 6.9) compared with males (mean, 6.1; 95% CI, 6.0 to
6.3). CONCLUSIONS: In a select group of patients who had joint pain following TJA
and no evidence of infection and who were referred for metal-sensitivity testing,
females exhibited a higher level of pain and demonstrated a higher rate and
severity (as measured by lymphocyte SI) of metal sensitization compared with
males. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for
a complete description of levels of evidence.
PMID- 28419030
TI - Ambulatory Total Shoulder Arthroplasty: A Comprehensive Analysis of Current
Trends, Complications, Readmissions, and Costs.
AB - BACKGROUND: There have been few studies that have evaluated ambulatory total
shoulder arthroplasty. The objectives of the present study were to investigate
the current trends in ambulatory total shoulder arthroplasty in the United
States; to characterize the rate of postoperative complications, hospital
readmission, and risk factors associated with readmission; and to conduct a cost
analysis comparing ambulatory total shoulder arthroplasty with matched inpatient
total shoulder arthroplasty. METHODS: A national insurance database was queried
for patients who underwent anatomic total shoulder arthroplasty between the
fourth quarter of 2010 and 2014. Patients undergoing ambulatory total shoulder
arthroplasty and a matched group of patients undergoing inpatient total shoulder
arthroplasty were identified. Complications were assessed for both groups. Risk
factors for readmission within 90 days postoperatively were examined. The costs
up to 30 days postoperatively were evaluated for patients who underwent
ambulatory total shoulder arthroplasty and controls. RESULTS: Included in the
study were 706 patients who underwent ambulatory total shoulder arthroplasty.
From the fourth quarter of 2010 to 2014, the yearly incidence of ambulatory total
shoulder arthroplasty doubled. In the study, 4,459 patients who underwent
inpatient total shoulder arthroplasty were matched to patients who underwent
ambulatory total shoulder arthroplasty. In no instances were any complications
present at a significantly higher rate in the patients who underwent ambulatory
total shoulder arthroplasty. The rate of readmission was not significantly
different (p > 0.05) between the 2 cohorts. The patients undergoing ambulatory
total shoulder arthroplasty had significantly lower costs (p < 0.0001) at $14,722
compared with the matched controls at $18,336 in numerous itemized cost
categories as well as costs related to diagnosis-related groups. CONCLUSIONS: In
appropriately selected patients, ambulatory total shoulder arthroplasty is a
viable and safe practice model. Ambulatory total shoulder arthroplasty also
offers significant cost savings compared with inpatient total shoulder
arthroplasty in matched patients. LEVEL OF EVIDENCE: Therapeutic Level III. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 28419031
TI - Prognostic Factors Affecting Union After Ulnar Shortening Osteotomy in Ulnar
Impaction Syndrome: A Retrospective Case-Control Study.
AB - BACKGROUND: Ulnar shortening osteotomy (USO) is a widely adopted procedure with
excellent outcomes. However, delayed union or nonunion has occasionally been
observed. The purpose of this retrospective case-control study was to identify
variables affecting osseous consolidation after USO in patients with ulnar
impaction syndrome. METHODS: The study included 325 patients who had undergone
USO between March 2008 and March 2014. We evaluated the association between union
and basic demographic factors as well as preoperative pain (assessed on a visual
analog scale [VAS]), range of wrist motion, grip strength, and modified Mayo
wrist score. We also assessed the association of union with radiographic
variables such as the degree of dorsal subluxation of the ulna, preoperative and
postoperative ulnar variance, morphological type of the distal radioulnar joint,
gap at the osteotomy site, and presence of newly developed arthritic changes
during the follow-up period. Finally, variables associated with operative
conditions, such as degeneration of the triangular fibrocartilage complex, use of
a parallel double-blade saw, type of plate used for fixation, number of screws,
and plate position on the volar or dorsal ulnar surface were investigated.
RESULTS: Ulnar union was achieved in 294 patients (group 1), and 31 patients had
delayed union or nonunion (group 2). On univariate and multivariate analyses,
smoking, low bone mineral density (BMD), a decreased range of motion of the
wrist, and use of a double-blade saw were found to be significant factors for an
adverse radiographic outcome (nonunion or delayed union). CONCLUSIONS: Delayed
union or nonunion occurred in about 10% of patients treated with USO. We suggest
that it may be preferable to perform USO in nonsmokers, patients with normal bone
density, and those without restricted wrist motion. Also, we recommend the use of
a single-blade saw when performing the osteotomy. LEVEL OF EVIDENCE: Therapeutic
Level III. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 28419032
TI - Formal Physical Therapy After Total Hip Arthroplasty Is Not Required: A
Randomized Controlled Trial.
AB - BACKGROUND: The value of formal physical therapy after total hip arthroplasty is
unknown. With substantial changes that have occurred in surgical and anesthesia
techniques, self-directed therapy may be efficacious in restoring function to
patients undergoing total hip arthroplasty. METHODS: We conducted a single
center, randomized trial of 120 patients undergoing primary, unilateral total hip
arthroplasty who were eligible for direct home discharge. The experimental group
followed a self-directed home exercise program for 10 weeks. The control group
received the standard protocol for physical therapy that included in-home visits
with a physical therapist for the first 2 weeks followed by formal outpatient
physical therapy for 8 weeks. Functional outcomes were measured using validated
instruments including the Harris hip score (HHS), the Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 Health
Survey (SF-36) preoperatively, at 1 month postoperatively, and at 6 to 12 months
postoperatively. RESULTS: Of 120 randomized patients, 108 were included in the
final analysis. Ten patients (19%) were randomized to unsupervised home exercise
and 20 patients (37%) were randomized to formal outpatient therapy crossed over
between groups. There was no significant difference in any of the measured
functional outcomes between patients receiving formal therapy (n = 54) and those
participating in unsupervised home exercise (n = 54) at any time point (HHS, p =
0.82; WOMAC, p = 0.80; and SF-36 physical health, p = 0.90). CONCLUSIONS: This
randomized trial suggests that unsupervised home exercise is both safe and
efficacious for a majority of patients undergoing total hip arthroplasty, and
formal physical therapy may not be required. LEVEL OF EVIDENCE: Therapeutic Level
I. See Instructions for Authors for a complete description of levels of evidence.
PMID- 28419034
TI - Complications and Functional Outcomes After Pantalar Dislocation.
AB - BACKGROUND: Pantalar dislocations without associated talar fracture are rare and
have high risks of complications, including infection, osteonecrosis, and
posttraumatic osteoarthrosis. Limited information on later function exists. This
study evaluated complications and outcomes following pantalar dislocation without
talar fracture. METHODS: Nineteen patients were identified with open (n = 14) or
closed (n = 5) pantalar dislocations without talar fracture. Ten male and 9
female patients with a mean age of 39.6 years (range, 19 to 68 years) were
included. Open injuries underwent surgical debridement. Sixteen patients had open
reduction, and 2 had closed reduction. Fixation was achieved with Kirschner wires
(n = 4), external fixation (n = 9), or both (n = 3). Two patients did not have
fixation. Another patient had primary transtibial amputation due to
nonreconstructible foot trauma. Charts and radiographs were reviewed to identify
infection, osteonecrosis, and posttraumatic arthrosis. Data on pain, medications,
range of motion, and secondary procedures were collected. After a minimum of 1
year, Foot Function Index (FFI) and Musculoskeletal Function Assessment (MFA)
surveys were administered. RESULTS: The mean clinical follow-up was 45.1 months.
Two patients had superficial wound-healing problems with prolonged drainage,
which healed with dressing changes and oral antibiotics, and 1 patient developed
cellulitis 4 months after injury, which resolved with intravenous antibiotics. No
deep wound infections occurred. Fourteen (88%) of the 16 patients with a minimum
of 11 months of radiographic follow-up developed osteonecrosis, 2 with collapse
of the talar dome, and 7 (44%) developed arthrosis of >=1 peritalar articulation.
Outcome surveys were obtained for 11 (58%) of the 19 patients, at a mean of 5.2
years after injury. The mean MFA score was 30.3, and the mean FFI score was 25.3.
Six of 10 survey respondents had returned to employment, but 88% (14 of 16) of
the patients with radiographic and clinical follow-up reported at least mild pain
and 75% (12 of 16) were taking analgesics. CONCLUSIONS: Urgent surgical
debridement of open injuries and reimplantation of the talus after pantalar
dislocation was not associated with deep infection. Osteonecrosis occurred in the
majority of patients, but collapse was uncommon. Persistent pain and functional
limitations are frequent after pantalar dislocation, as reflected in extremity
specific and generalized functional outcome scores. LEVEL OF EVIDENCE:
Therapeutic Level IV. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 28419035
TI - Clinical Practice Guidelines Decrease Unnecessary Echocardiograms Before Hip
Fracture Surgery.
AB - BACKGROUND: Preoperative assessment of geriatric patients with a hip fracture may
include transthoracic echocardiography (TTE), which increases resource
utilization and cost and may delay surgery. The purpose of this study was to
evaluate preoperative TTE utilization at a single institution in order to
determine (1) how often TTE is ordered in accordance with clinical practice
guidelines (CPGs), (2) how frequently TTE reveals cardiac disease that may alter
medical or anesthesia management, and (3) whether following CPGs reduces
unnecessary TTE utilization without potentially missing important disease.
METHODS: A retrospective review of data on 100 geriatric patients with a hip
fracture who had undergone preoperative TTE was performed. Charts were reviewed
to evaluate if TTE had been obtained in accordance with the published CPGs from
the American College of Cardiology/American Heart Association (ACC/AHA). TTE
reports were reviewed for the presence of disease that was important enough to
cause modifications in anesthesia or perioperative management, including new left
ventricular systolic or diastolic dysfunction, moderate or severe valvular
disease, and pulmonary hypertension. Finally, the sensitivity and specificity of
accordance with the ACC/AHA CPGs for predicting which patients would have TTE
that identified important disease were calculated. RESULTS: The TTE was ordered
in accordance with the published ACC/AHA CPGs for 66% of the patients. TTE
revealed disease with the potential to modify anesthesia or medical management in
14% of the patients-for all of whom the TTE had been indicated according to
ACC/AHA guidelines (i.e., the guidelines were 100% sensitive). In this study
population, following the ACC/AHA guidelines could have prevented the performance
of TTE in 34% of the patients without missing any disease (40% specificity).
CONCLUSIONS: Preoperative TTE for patients with a hip fracture is frequently
obtained outside the recommendations of established CPGs. Utilization of CPGs
such as the ACC/AHA guidelines should be considered, as it may decrease
variability in care and reduce unnecessary resource utilization without adversely
affecting patient outcomes.
PMID- 28419033
TI - Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics
for Periprosthetic Joint Infection: Study of a Mouse Model.
AB - BACKGROUND: The medical treatment of periprosthetic joint infection (PJI)
involves prolonged systemic antibiotic courses, often with suboptimal clinical
outcomes including increased morbidity and health-care costs. Oral and
intravenous monotherapies and combination antibiotic regimens were evaluated in a
mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. METHODS:
Oral linezolid with or without oral rifampin, intravenous vancomycin with oral
rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin,
oral doxycycline, or sham treatment were administered at human-exposure doses for
6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo
bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and
reactive bone changes were evaluated with radiographs and micro-computed
tomography (MUCT) imaging. RESULTS: Oral-only linezolid-rifampin and all
intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria
and minimized reactive bone changes. Although oral linezolid was the most
effective monotherapy, all oral and intravenous antibiotic monotherapies failed
to clear infection or prevent reactive bone changes. CONCLUSIONS: Combination
antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the
newer ceftaroline-rifampin combinations, were highly effective and more
efficacious than monotherapies when used against a preclinical MRSA PJI. CLINICAL
RELEVANCE: This study provides important preclinical evidence to better optimize
future antibiotic therapy against PJIs. In particular, the oral-only linezolid
rifampin option might reduce venous access complications and health-care costs.
PMID- 28419036
TI - Emerging U.S. National Trends in the Treatment of Pediatric Supracondylar Humeral
Fractures.
AB - BACKGROUND: Understanding national trends in the treatment of pediatric
supracondylar humeral fractures will provide important insight into variations in
regional treatment and identify areas for improving value and quality in care
delivery in the U.S. METHODS: U.S. national trends in the treatment of
supracondylar humeral fractures were evaluated through query of the Humana (2007
to 2014) and ING (2007 to 2011) administrative claims databases. Geographic
variation and changes in surgical and transfer rates over time were further
explored through the Nationwide Emergency Department Sample (NEDS) database (2006
to 2011). Hospital characteristics impacting treatment decisions were identified.
RESULTS: A total of 29,642 pediatric patients with supracondylar humeral
fractures were identified in the administrative claims databases and a projected
63,348 encounters for supracondylar humeral fracture were identified in the NEDS
database. The majority of the patients (76.1%; 22,563 of 29,642) were treated
definitively with cast immobilization. Operative treatment was performed in 23.9%
of the patients (7,079 of 29,642), with no change observed in the operative rate
over time (p = 0.055). Of patients undergoing operative treatment, closed
reduction and percutaneous pinning (CRPP) was performed in 87.3%, with a
significant increase noted in the rate of CRPP over time (p = 0.0001); open
reduction was performed in 12.7%, with a significant decrease noted in the rate
of open reduction over time (p < 0.0001). Regional surgical rates generally
showed significant variation from 2006 to 2010, followed by a convergence in the
surgical rate among all geographic regions in 2011. These trends occurred
simultaneous to a significant increase in transfer rates nationwide, from 5.6% in
2006 to 9.1% in 2011 (p = 0.0011). Transfer rates were significantly higher (p <
0.0001) for nontrauma, nonteaching, and nonmetropolitan centers while surgical
rates were significantly higher (p < 0.0001) for trauma, teaching, and
metropolitan centers when rates were analyzed by hospital designation.
CONCLUSIONS: Operative treatment was performed in 24% of pediatric patients with
supracondylar humeral fractures from 2007 to 2014. There was a convergence of
surgical rates across geographic regions, suggesting that a "standard of care" in
the treatment of supracondylar humeral fractures is being established nationally.
CLINICAL RELEVANCE: Cases of pediatric supracondylar humeral fracture are
increasingly being transferred to and, when managed surgically, receiving care at
metropolitan facilities designated as trauma centers or teaching hospitals, with
a corresponding decrease observed in the rate of open reduction. The optimization
of nationwide referral and treatment patterns may improve value in care delivery.
PMID- 28419037
TI - Depression and Patient-Reported Outcomes Following Total Shoulder Arthroplasty.
AB - BACKGROUND: Recent studies have found that depression is associated with
increased pain and impairment following lower-extremity arthroplasty; however,
this association has not been investigated for total shoulder arthroplasty. The
objective of this study was to investigate the association between depression and
patient-reported outcomes following total shoulder arthroplasty. METHODS: A
prospectively collected institutional registry was queried for consecutive
patients who underwent total shoulder arthroplasty for osteoarthritis from 2007
to 2013 with baseline and minimum 2-year postoperative American Shoulder and
Elbow Surgeons (ASES) scores. Revision procedures and total shoulder arthroplasty
for diagnoses other than osteoarthritis were excluded. Patients with a
preoperative diagnosis of depression (n = 88) formed the study cohort; control
patients without a diagnosis of depression were matched to the study patients by
age and sex in a 2:1 ratio (n = 176). Baseline characteristics and patient
reported outcome measures were compared between groups, as were minimum 2-year
patient-reported outcomes and change in patient-reported outcomes. A
multivariable regression was performed to investigate the independent effect of
depression on improvement in ASES scores. RESULTS: Except for the Short Form-12
Mental Component Summary (SF-12 MCS) scores, there were no significant
differences (p > 0.05) in baseline characteristics between study patients and
controls. There was a significant improvement in the ASES score for patients with
depression (p < 0.0001) and controls (p < 0.0001). Patients with depression had
significantly lower final ASES scores (p = 0.001) and less improvement in ASES
scores (p = 0.001) and SF-12 Physical Component Summary scores (p = 0.006) as
well as lower satisfaction levels at 2 years; however, the latter difference did
not reach clinical importance. Depression (p = 0.018) was an independent
predictor of less improvement in ASES scores. CONCLUSIONS: Patients with a
diagnosis of depression should be counseled that they will experience a
significant clinical improvement from baseline after total shoulder arthroplasty.
A preoperative diagnosis of depression is an independent predictor of
significantly less improvement in ASES scores following total shoulder
arthroplasty; however, this difference does not reach clinical importance and
should not discourage patients with a clinical diagnosis of depression from
undergoing total shoulder arthroplasty. LEVEL OF EVIDENCE: Prognostic Level III.
See Instructions for Authors for a complete description of levels of evidence.
PMID- 28419038
TI - The American Academy of Orthopaedic Surgeons Appropriate Use Criteria for
Surgical Management of Osteoarthritis of the Knee.
PMID- 28419039
TI - What's New in Foot and Ankle Surgery.
PMID- 28419040
TI - Measurement of Distal Ulnar Hounsfield Units Accurately Predicts Bone Mineral
Density of the Forearm.
AB - BACKGROUND: Hounsfield unit (HU) measurement obtained from computed tomography
(CT) scans of the wrist is a potential new screening method for low bone mineral
density (BMD). We hypothesized that HU measurements of the ulnar head obtained
from CT scans would correlate with BMD assessed with dual x-ray absorptiometry
(DXA) scans of the forearm. METHODS: Patients with both upper-extremity CT and
DXA scans performed at a single institution were included in the study.
Hounsfield units were manually measured in the distal part of the ulna by 1
author blinded to the DXA results. Average values were then compared with forearm
BMD values as determined with a DXA scan. RESULTS: Seventy-seven CT scans of 74
patients were included. Average HU values were significantly lower in the
osteoporotic and osteopenic groups in comparison with the normal BMD group. The
upper limit of the 95% confidence interval for osteopenic patients was 145.9 HU.
The average forearm T-score for patients with an HU value at or below the cutoff
of 146 was significantly lower than the average T-score for those with an HU
value of >146 HU (p < 0.0001). Sensitivity and negative predictive value for low
BMD using this cutoff value were calculated to be 91% and 89%, respectively.
CONCLUSIONS: Distal ulnar HU measurements accurately reflect the BMD of the
forearm as diagnosed with a DXA scan. Our results suggest that distal ulnar HU
measurements of <=146 HU are strongly associated with low BMD and that values
above this cutoff accurately rule out low forearm BMD with a high degree of
sensitivity and negative predictive value. Utilizing this technique may improve
the capture of at-risk patients and streamline the screening process for
osteoporosis. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for
Authors for a complete description of levels of evidence.
PMID- 28419041
TI - Accuracy of Computer-Aided Techniques in Orthopaedic Surgery: How Can It Be
Defined, Measured Experimentally, and Analyzed from a Clinical Perspective?
AB - Surgical accuracy is multifactorial. Therefore, it is crucial to consider all
influencing factors when investigating the accuracy of a surgical procedure, such
as the surgeon's experience, the assistive technologies that may be used by the
surgeon, and the patient factors associated with the specific anatomical site.
For in vitro preclinical investigations, accuracy should be linked to the
concepts of trueness (e.g., distance from the surgical target) and precision
(e.g., variability in relation to the surgical target) to gather preclinical,
quantitative, objective data on the accuracy of completed surgical procedures
that have been performed with assistive technologies. The clinical relevance of
improvements in accuracy that have been observed experimentally may be evaluated
by analyzing the impact on the risk of failure and by taking into account the
level of tolerance in relation to the surgical target (e.g., the extent of the
safety zone). The International Organization for Standardization (ISO)
methodology enables preclinical testing of new assistive technologies to quantify
improvements in accuracy and assess the benefits in terms of reducing the risk of
failure and achieving surgical targets with tighter tolerances before the testing
of clinical outcomes.
PMID- 28419042
TI - Geriatric Fracture Care: Future Trajectories: A 2015 AOA Critical Issues
Symposium.
AB - The population of the United States and the world is aging rapidly.
Musculoskeletal care for older adults will be impacted by the manner in which
health care is financed and the ability of the orthopaedic community to provide
evidence-based integrated care for this population. We review the financial
aspects of health-care reform and the implications for musculoskeletal care in
the elderly. We discuss the establishment of quality measures for hip fracture
care in the elderly, team building to accomplish this, and an innovative program
designed to provide orthopaedic care to the frail elderly outside of the usual
office setting.
PMID- 28419043
TI - Confirmation of Sexual Dimorphisms in Metal Hypersensitivity and Joint Pain
Following Total Joint Arthroplasty: Commentary on an article by Marco S. Caicedo,
PhD, et al.: "Females with Unexplained Joint Pain Following Total Joint
Arthroplasty Exhibit a Higher Rate and Severity of Hypersensitivity to Implant
Metals Compared with Males. Implications of Sex-Based Bioreactivity Differences".
PMID- 28419044
TI - Resiliency Is Good for You: Commentary on an article by Brian C. Werner, MD, et
al.: "Depression and Patient-Reported Outcomes Following Total Shoulder
Arthroplasty".
PMID- 28419045
TI - Ultrasound Guidance for Trigger Point Injections: Gold Standard or Fool's Gold?
PMID- 28419046
TI - Point-of-Care Ultrasound for the Regional Anesthesiologist and Pain Specialist: A
Series Introduction.
PMID- 28419047
TI - The Subsartorial Approach to the Continuous Adductor Canal Block: Safer?
PMID- 28419048
TI - Reply to Dr Kelly et al.
PMID- 28419049
TI - An Anatomical Basis for Naming Plane Blocks of the Anteromedial Chest Wall.
PMID- 28419050
TI - Periosteal Infusion of Local Anesthetics as an Alternative to Bilateral
Subpectoral Interfascial Plane Catheters in Patients With Sternal Fractures.
PMID- 28419051
TI - Reply to Dr Eid et al.
PMID- 28419052
TI - It's Not Just About the Diaphragm.
PMID- 28419053
TI - Reply to Dr Price.
PMID- 28419054
TI - Local Anesthetic Diffusion of Bilateral Sternal Block After Cardiac Surgery.
PMID- 28419055
TI - Be the Change: An Interprofessional Team-Based Health Advocacy Summit.
AB - In a complex health care environment, nursing and health care professional
graduates should be able to understand and collaboratively advocate for health
policy benefitting patients, families, and communities. This study explored the
effectiveness of interprofessional team-based learning to improve political
astuteness in undergraduate health profession students. This engaging method may
prove to enhance health care professionals' likelihood of understanding,
involvement, and influencing health policy in the future.
PMID- 28419056
TI - Response characteristics of the rat anterior cingulate cortex to ultrasonic
communicative vocalizations.
AB - Emotional communication involves transmitting information on affective states.
Rat 50- and 22-kHz ultrasonic vocalizations (USVs) are emotional communication
signals that reflect positive or negative states, respectively. In general,
emotional communication signals that elicit changes in event-related potentials
(ERPs), suggesting a specific mechanism for processing these signals. As this is
observed in several communication systems including humans, we hypothesized that
rat USVs can also trigger such changes. In this study, we measured rat local
field potentials and used them to calculate ERPs from the anterior cingulate
cortex (ACC), an area related to motor production of USVs. In Experiment 1, we
measured ERPs to pure tones with peak frequencies around 50 or 22 kHz to examine
whether the ACC is involved in auditory sensory processing related to pitch. The
results showed that pure tones around 50 kHz elicited large amplitude ERPs,
whereas those around 22 kHz resulted in smaller ERPs. In Experiment 2, we
compared ERPs in response to rat USVs (emotional stimuli) with ERPs to pure tones
modeled after USVs (neutral stimuli). The peak frequencies were the same between
USVs and neutral sounds, but USVs showed more frequency modulation than neutral
sounds. USVs elicited larger changes in the amplitude of ERP components than
neutral stimuli did. These experiments suggest that the rat ACC is sensitive to
frequencies around 50 and 22 kHz, and is especially tuned to frequency modulation
around these frequencies. Taken together, the rat ACC may process the emotional
content of communication signals on the basis of pitch and frequency modulation.
PMID- 28419057
TI - GABAergic modulation of noradrenaline release caused by blood pressure changes in
the rat median preoptic area.
AB - Experiments using in-vivo microdialysis methods were conducted to investigate
whether blood pressure changes cause an alteration in the release of
noradrenaline (NA) in the median preoptic nucleus (MnPO) and whether the gamma
aminobutyric acid (GABA) receptor mechanism is involved in the modulation of the
pressure response-induced alteration in the NA release. In urethane-anesthetized
male rats, intravenous administration of metaraminol, an alpha-agonist,
significantly produced an increase in dialysate NA concentration in the MnPO area
accompanied by an elevation in the mean arterial pressure (MAP). Perfusion with
GABA (10 MUM) through the dialysis probe elicited a significant decrease in
either MAP or the NA concentration in the MnPO area. Similar perfusion with
either the GABAA receptor antagonist bicuculline (10 MUM) or the GABAB receptor
antagonist phaclofen (10 MUM) caused a significant increase in both MAP and the
NA release in the MnPO area. Either bicuculline or phaclofen administered
together with the metaraminol further enhanced the metaraminol-induced MAP and NA
release in the MnPO area. The degree of increases in the both MAP of the NA
release was significantly greater in the bicuculline-treated group than in the
phaclofen-treated group. These results suggest that the NA release in the MnPO
area may be potentiated during an elevation in arterial pressure caused by the
metaraminol injection and imply that the NA release may be mediated through GABAA
receptors rather than GABAB receptors in the MnPO area.
PMID- 28419058
TI - A method for u-fiber quantification from 7 T diffusion-weighted MRI data tested
in patients with nonlesional focal epilepsy.
AB - In this methods development, we present an ultra-high-field, diffusion-weighted
MRI method to quantitatively assess u-fibers and use it to compare u-fiber counts
in nonlesional epilepsy patients with controls. Emerging evidence implicates
white matter abnormalities in nonlesional epilepsy, including the short-range,
cortical-cortical connections, or u-fibers. Eight patients with nonlesional
epilepsy and eight demographically matched controls underwent 7 T MRI consisting
of a T1-weighted sequence (0.7 mm isotropic resolution) and high-angular-resolved
diffusion-weighted MRI (1.05 mm isotropic resolution, 68 directions). MRI data
were used to quantify u-fiber counts in known u-fiber populations on the basis of
an atlas and fiber tractography. From tractography, connectivity matrices
summarizing the u-fiber counts were computed. Quantitative group comparisons were
performed on the connectivity matrices. U-fiber counts were found to be lower on
average in patients with epilepsy than in healthy controls. The results indicate
that the density or the number of u-fibers is reduced in patients with
nonlesional epilepsy. Future work will focus on histological validation and
determining whether differences in u-fiber counts can be used clinically to
noninvasively identify seizure-onset zones.
PMID- 28419059
TI - Late-onset nivolumab-mediated pneumonitis in a patient with melanoma and multiple
immune-related adverse events.
AB - Immune-related adverse effects (AEs) of PD-1 inhibitors can affect almost every
organ, but the skin, intestine, lung, eye, and liver are the most commonly
affected organs. Here, we present the case of a 62-year-old female patient with
stage IIIc melanoma treated with nivolumab in an adjuvant setting who
sequentially developed hyperthyroidism, hypothyroidism, acute hepatitis, and
pneumonitis. Six months before the emergence of pneumonitis, the patient had
discontinued treatment with nivolumab because of acute hepatitis. Information on
pneumonitis after nivolumab discontinuation in the literature is scarce, whereas
most of the cases emerge during the first 2.5 months of treatment. Patients with
multiple immune-related AEs comprise a group of special interest as the
identification of factors affecting the susceptibility of patients to immune
related AEs of PD-1 inhibitors may lead to a more rational use of these drugs.
Human leukocyte antigen haplotype and Fcgamma receptor polymorphisms are possible
targets of the relevant research.
PMID- 28419060
TI - Relationship of Hospital Costs With Mortality in Pediatric Critical Care: A Multi
Institutional Analysis.
AB - OBJECTIVE: With increasing emphasis on high "value" care, we designed this study
to evaluate the relationship between hospital costs and patient outcomes in
pediatric critical care. DESIGN: Post hoc analysis of data from an existing
administrative national database, Pediatric Health Information Systems.
Multivariable mixed effects logistic regression models were fitted to evaluate
association of hospital cost tertiles with odds of mortality after adjusting for
patient and center characteristics. SETTING: Forty-seven children's hospitals
across the United States. PATIENTS: Patients 18 years old or younger admitted to
a PICU at a Pediatric Health Information Systems participating hospital were
included (2004-2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total
of 917,663 patients from 47 hospitals were included. Median cost per patient was
$42,181 in the low-cost hospitals (341,689 patients, 16 hospitals), $56,806 in
the middle-cost hospitals (310,293 patients, 16 hospitals), and $82,588 in the
high-cost hospitals (265,681 patients, 15 hospitals). In unadjusted analysis,
patients cared for in the high-cost tertile hospitals were younger in age,
associated with more comorbidities, had higher resource utilization (including
extracorporeal membrane oxygenation and nitric oxide), had higher prevalence of
cardiac arrest, and were associated with worse outcomes (including mortality). In
adjusted analysis, high-cost tertile hospitals were not associated with improved
mortality, when compared with low- and medium-cost tertile hospitals (low cost vs
high cost: odds ratio, 0.99; 95% CI, 0.79-1.25 and middle cost vs high cost: odds
ratio, 1.10; 95% CI, 0.86-1.41). When stratified by diagnoses category, we noted
similar trends among cardiac and noncardiac patients. CONCLUSIONS: This large
observational study did not demonstrate any relationship between hospital costs
and patient outcomes in children with critical illness. Further efforts are
needed to evaluate quality-cost relationship and high value care in critically
ill children across centers of varying volume by linking data from clinical and
administrative databases.
PMID- 28419061
TI - Functional Status of Neonatal and Pediatric Patients After Extracorporeal
Membrane Oxygenation.
AB - OBJECTIVES: To describe functional status at hospital discharge for neonatal and
pediatric patients treated with extracorporeal membrane oxygenation, and identify
factors associated with functional status and mortality. DESIGN: Secondary
analysis of observational data collected by the Collaborative Pediatric Critical
Care Research Network between December 2012 and September 2014. SETTING: Eight
hospitals affiliated with the Collaborative Pediatric Critical Care Research
Network. PATIENTS: Patients were less than 19 years old and treated with
extracorporeal membrane oxygenation. INTERVENTIONS: Functional status was
evaluated among survivors using the Functional Status Scale. Total Functional
Status Scale scores range from 6 to 30 and are categorized as 6-7 (good), 8-9
(mildly abnormal), 10-15 (moderately abnormal), 16-21 (severely abnormal), and
greater than 21 (very severely abnormal). MEASUREMENTS AND MAIN RESULTS: Of 514
patients, 267 (52%) were neonates (<= 30 d old). Indication for extracorporeal
membrane oxygenation was respiratory for 237 (46%), cardiac for 207 (40%), and
extracorporeal cardiopulmonary resuscitation for 70 (14%). Among 282 survivors,
89 (32%) had good, 112 (40%) mildly abnormal, 67 (24%) moderately abnormal, and
14 (5%) severely or very severely abnormal function at hospital discharge. Among
neonates, development of renal failure and longer hospitalization were
independently associated with worse Functional Status Scale. Chronic conditions,
prematurity, venoarterial extracorporeal membrane oxygenation, increased red cell
transfusion in the first 24 hours of extracorporeal membrane oxygenation, and
longer extracorporeal membrane oxygenation duration were independently associated
with mortality. Among pediatric patients, chronic neurologic conditions,
tracheostomy or home ventilator, extracorporeal cardiopulmonary resuscitation,
hepatic dysfunction, and longer ICU stay were independently associated with worse
Functional Status Scale. Chronic cardiac conditions, hepatic dysfunction, and
neurologic or thrombotic complications were independently associated with
mortality. Achieving blood lactate concentration less than or equal to 2 mmol/L
during extracorporeal membrane oxygenation was independently associated with
survival in both neonatal and pediatric patients. CONCLUSIONS: In this study,
about half of extracorporeal membrane oxygenation patients survived with good,
mildly abnormal, or moderately abnormal function at hospital discharge. Patient
and extracorporeal membrane oxygenation-related factors are associated with
functional status and mortality.
PMID- 28419062
TI - Single-Center Study Investigating Foreign Language Acquisition at School in
Children, Adolescents, and Young Adults With Uni- or Bilateral Cochlear Implants
in the Swiss German Population.
AB - OBJECTIVE: To evaluate foreign language acquisition at school in cochlear implant
patients. STUDY DESIGN: Cohort study. SETTING: CI center. PATIENTS: Forty three
cochlear implants (CI) patients (10-18 yr) were evaluated. CI nonusers and
patients with CI-explantation, incomplete datasets, mental retardation, or
concomitant medical disorders were excluded. INTERVENTION(S): Additional data
(type of schooling, foreign language learning, and bilingualism) were obtained
with questionnaires. German-speaking children with foreign tuition language
(English and/or French) at school were enrolled for further testing. MAIN OUTCOME
MEASURE(S): General patient data, auditory data, and foreign language data from
both questionnaires and tests were collected and analyzed. RESULTS: Thirty seven
out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream
education. Twenty-seven CI users (73%) have foreign language learning at school.
Fifteen of these were in mainstream education (55%), others in special schooling.
From 10 CI users without foreign language learning, one CI user was in mainstream
education (10%) and nine patients (90%) were in special schooling. Eleven German
speaking CI users were further tested in English and six additionally in French.
For reading skills, the school objectives for English were reached in 7 of 11
pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11
pupils (27%) reached the school norm in English and none in French. CONCLUSIONS:
Almost 75% of our CI users learn foreign language(s) at school. A small majority
of the tested CI users reached the current school norm for in English and French
in reading skills, whereas for hearing skills most of them were not able to reach
the norm.
PMID- 28419063
TI - The Effect of Elevated Intracranial Pressure on Frequency Tuning of Air-Conducted
Ocular Vestibular Myogenic Potentials in Meniere's Disease Patients.
AB - OBJECTIVE: To investigate the effect of increased intracranial pressure on ocular
vestibular-evoked myogenic potential (oVEMP) amplitudes and frequency tuning in
patients with Meniere's disease (MD) to elucidate whether oVEMPS recorded under
such conditions could provide a simple and accurate diagnostic test for MD.
SETTING: Tertiary referral center for otology and neurotology. PATIENTS: Ten
patients with certain unilateral MD (mean age = 48.2 yr, range 25-75 yr, 6 males
and 4 females) as confirmed by a locally enhanced inner ear MRI (LEIM) were
enrolled in this study. DESIGN: Air-conducted tone-burst oVEMP amplitudes were
measured in response to 500 Hz and 1000 Hz in the horizontal plane (0 degree), a
20-degree head-down position. RESULTS: Tilting the patients from the horizontal
position to the 20-degree head-down position led to a large reduction in oVEMP
amplitudes to the 500 Hz tone burst (3.02 MUV vs 1.17 MUV, p = 0.005) and to a
smaller one in the 1000 Hz tone burst (2.28 MUV vs 1.78 MUV, p = 0.013) in the
Meniere's ear. Accordingly, the 500/1000 Hz frequency-tuning ratio was
significantly decreased in the Meniere's ear as a result of this manoeuver (1.36
vs 0.75, p = 0.005). CONCLUSION: oVEMP amplitudes and frequency tuning in MD
patients show a similar behavior to that found in healthy control subjects. oVEMP
testing of putative MD patients in the tilted position is therefore unlikely to
be diagnostically useful.
PMID- 28419064
TI - The Application of Next-Generation Sequencing for Mutation Detection in Autosomal
Dominant Hereditary Hearing Impairment.
AB - OBJECTIVE: Identification of the causative mutation using next-generation
sequencing in autosomal-dominant hereditary hearing impairment, as mutation
analysis in hereditary hearing impairment by classic genetic methods, is hindered
by the high heterogeneity of the disease. PATIENTS: Two Swiss families with
autosomal-dominant hereditary hearing impairment. INTERVENTION: Amplified DNA
libraries for next-generation sequencing were constructed from extracted genomic
DNA, derived from peripheral blood, and enriched by a custom-made sequence
capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq
instrument, 300 cycles and paired-end sequencing. Technical data analysis was
performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The
detection of mutations in genes related to hearing loss by next-generation
sequencing was subsequently confirmed using specific polymerase-chain-reaction
and Sanger sequencing. MAIN OUTCOME MEASURE: Mutation detection in hearing-loss
related genes. RESULTS: The first family harbored the mutation c.5383+5delGTGA in
the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG
in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified.
CONCLUSION: Next-generation sequencing successfully identified the causative
mutation in families with autosomal-dominant hereditary hearing impairment. The
results helped to clarify the pathogenic role of a known mutation and led to the
detection of a novel one. NGS represents a feasible approach with great potential
future in the diagnostics of hereditary hearing impairment, even in smaller labs.
PMID- 28419065
TI - Late maternal age at last childbirth and telomere homeostasis.
PMID- 28419066
TI - Should postmenopausal women eat more protein? Or do the elite just exercise and
eat better?
PMID- 28419067
TI - Clinical use of ring with support pessary for advanced pelvic organ prolapse and
predictors of its short-term successful use.
AB - OBJECTIVE: This study aimed to evaluate the success rate, patient satisfaction
and adverse events with the use of the ring with support pessary in patients with
advanced pelvic organ prolapse (POP), and to identify the factors associated with
successful pessary use. METHODS: In this prospective study, 151 patients with
symptomatic advanced POP (POP quantification stage III/IV) came to the Centre of
Obstetrics and Gynaecology, Peking Union Medical College Hospital, for POP
treatment between May 2015 and December 2015. In all, 97 patients who chose the
ring with support pessaries were included in this study. Successful pessary use
was defined as the continuous use of the pessary at a 3-month follow-up visit.
Independent-samples t tests, nonparametric tests, chi-square tests, Fisher's
exact test, and logistic regression were used for data analysis. RESULTS: In all,
82 patients continued to use the ring with support pessary for 3 months, whereas
15 patients discontinued, corresponding to a success rate of 84.5% (82/97). Most
patients (80/82, 97.6%) who achieved success using the ring with support pessary
felt satisfied. No severe complications were observed. Size 3 was the most
commonly used size in our center (59.8% of the study patients). Predominant
anterior wall prolapse was associated with the successful use of ring with
support pessary (odds ratio 5.08, 95% confidence interval 1.33-19.43, P = 0.02).
CONCLUSIONS: The ring with support pessary was successfully used for the
treatment of advanced POP with high rates of success and satisfaction. A
predominant prolapse in the anterior wall may be a potential influence factor for
successful pessary use.
PMID- 28419068
TI - Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a
double-blind, placebo-controlled trial.
AB - OBJECTIVE: To evaluate the response of the vaginal mucosa with TX-004HR and its
correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual
examination is a useful measure for assessing VVA. METHODS: REJOICE was a 12
week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of
a vaginal, muco-adhesive, 17beta-estradiol softgel capsule (TX-004HR 4, 10, and
25 MUg) in postmenopausal women with VVA and moderate-to-severe dyspareunia.
Treatments were self-administered vaginally once per day for 2 weeks, then twice
per week for 10 weeks. The vagina was visually examined at baseline and at weeks
2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color,
vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal
secretions. RESULTS: Significant improvements were observed with all three TX
004HR doses versus placebo in vaginal color (least square mean score changes of
0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial
integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03
vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (P < 0.001 for all
comparisons at all time points). Both Pearson's correlations and logistic
regression receiver-operating characteristic curve analyses significantly
correlated the sum of the individual visual assessment scores with dyspareunia (P
< 0.0001) and vaginal dryness (P < 0.0001) at 12 weeks. CONCLUSIONS: Greater
improvements in the vaginal mucosa of postmenopausal women with VVA and moderate
to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal
mucosa assessment scores correlated with vaginal symptoms of dyspareunia and
dryness. Visual vaginal assessment by healthcare professionals is a useful
measure for diagnosing VVA and assessing response to treatment.
PMID- 28419070
TI - Another link between exercise and relief from postmenopausal decline.
PMID- 28419069
TI - Postmenopausal sleep disturbance and sexual dysfunction.
PMID- 28419071
TI - Reduction of cardiovascular risk with evolocumab (Repatha).
PMID- 28419072
TI - Dupilumab (Dupixent) for moderate to severe atopic dermatitis.
PMID- 28419073
TI - Plecanatide (Trulance) for chronic idiopathic constipation.
PMID- 28419074
TI - Arymo ER--a new abuse-deterrent morphine formulation.
PMID- 28419075
TI - In brief: New adult immunization recommendations.
PMID- 28419076
TI - In brief: Pancreatitis with eluxadoline (Viberzi) in patients without a
gallbladder.
PMID- 28419077
TI - OTC fluticasone furoate nasal spray (Flonase Sensimist) for allergic rhinitis.
PMID- 28419078
TI - Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis.
AB - BACKGROUND: MicroRNAs (miRs) are involved in the regulation of many processes
that contribute to malignancy, including cell proliferation, radiation
resistance, invasion and metastasis. The role of miR-330-3p, an miR upregulated
in breast cancer, remains unclear. METHODS: We examine the association of miR-330
3p with distant relapse-free survival in the Oxford cohort of breast cancer
patients. We also study miR-330-3p function using in vitro invasion and ex ovo
metastasis assays. Using in vitro luciferase assays, we validate a novel target
gene for miR-330-3p, Collagen And Calcium Binding EGF Domains 1 (CCBE1). We
assess functional consequences of CCBE1 loss by using siRNA-mediated knockdown
followed by in vitro invasion assays. Lastly, we examine the expression profile
of CCBE1 in breast carcinomas in the Curtis and TCGA Breast Cancer data sets
using Oncomine Platform as well as distant relapse-free and overall survival of
patients in the Helsinki University breast cancer data set according to CCBE1
expression status. RESULTS: miR-330-3p is enriched in breast cancer, and higher
levels of miR-330-3p expression are associated with lower distant relapse-free
survival in a cohort of breast cancer patients. Consistent with these
observations, overexpression of miR-330-3p in breast cancer cell lines results in
greater invasiveness in vitro, and miR-330-3p-overexpressing cells also
metastasise more aggressively ex ovo. We identify CCBE1 as a direct target of miR
330-3p, and show that knockdown of CCBE1 results in a greater invasive capacity.
Accordingly, in breast cancer patients CCBE1 is frequently downregulated, and its
loss is associated with reduced distant relapse-free and overall survival.
CONCLUSIONS: We show for the first time that miR-330-3p targets CCBE1 to promote
invasion and metastasis. miR-330-3p and CCBE1 may represent promising biomarkers
in breast cancer.
PMID- 28419080
TI - Heteromolecular phases: Opposite interaction matters.
PMID- 28419079
TI - Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment
diffuse optical spectroscopic texture analysis.
AB - BACKGROUND: Diffuse optical spectroscopy (DOS) has been demonstrated capable of
monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast
cancer (LABC) patients. In this study, we evaluate texture features of
pretreatment DOS functional maps for predicting LABC response to NAC. METHODS:
Locally advanced breast cancer patients (n=37) underwent DOS breast imaging
before starting NAC. Breast tissue parametric maps were constructed and texture
analyses were performed based on grey-level co-occurrence matrices for feature
extraction. Ground truth labels as responders (R) or non-responders (NR) were
assigned to patients based on Miller-Payne pathological response criteria. The
capability of DOS textural features computed on volumetric tumour data before the
start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was
evaluated using a leave-one-out validation scheme at subject level. Data were
analysed using a logistic regression, naive Bayes, and k-nearest neighbour
classifiers. RESULTS: Data indicated that textural characteristics of
pretreatment DOS parametric maps can differentiate between treatment response
outcomes. The HbO2 homogeneity resulted in the highest accuracy among univariate
parameters in predicting response to chemotherapy: sensitivity (%Sn) and
specificity (%Sp) were 86.5% and 89.0%, respectively, and accuracy was 87.8%. The
highest predictors using multivariate (binary) combination features were the Hb
contrast+HbO2-homogeneity, which resulted in a %Sn/%Sp=78.0/81.0% and an accuracy
of 79.5%. CONCLUSIONS: This study demonstrated that the pretreatment DOS texture
features can predict breast cancer response to NAC and potentially guide
treatments.
PMID- 28419081
TI - Prepubertal children born large for gestational age have lower serum DHEAS
concentrations than those with a lower birth weight.
AB - BackgroundChildren born small for gestational age (SGA) have higher serum
dehydroepiandrosterone sulfate (DHEAS) concentrations than children born
appropriate for gestational age (AGA). The overall metabolic risk associated with
birth weight is U-shaped, but it is not known whether children born large for
gestational age (LGA) have elevated serum DHEAS levels.MethodsA cohort of 49
children born LGA, 56 children born AGA, and 23 children born SGA were studied at
5-8 years of age. Anthropometric data at birth, at the age of 2 years, and at
examination were recorded. Fasting blood samples were collected for serum
analyses of DHEAS, insulin-like growth factor 1 (IGF-1), and insulin
concentrations.ResultsThe children born LGA had lower serum DHEAS levels adjusted
for body mass index (BMI) standard deviation score (SDS) and age than the rest of
the children. Lower birth weight SDS and higher weight gain during the first 2
years of life predicted higher serum DHEAS levels. Higher serum IGF-1 levels were
also associated with higher prevalence of adrenarchal DHEAS
levels.ConclusionBeing born LGA was associated with lower DHEAS levels, whereas
small birth size and early catch-up growth predicted higher levels. This suggests
that genetic or early epigenetic factors have an impact on adrenarche. IGF-1 may
be a mediator in this process.
PMID- 28419082
TI - Diffuse optical tomography to investigate the newborn brain.
AB - Over the past 15 years, functional near-infrared spectroscopy (fNIRS) has emerged
as a powerful technology for studying the developing brain. Diffuse optical
tomography (DOT) is an extension of fNIRS that combines hemodynamic information
from dense optical sensor arrays over a wide field of view. Using image
reconstruction techniques, DOT can provide images of the hemodynamic correlates
to neural function that are comparable to those produced by functional magnetic
resonance imaging. This review article explains the principles of DOT, and
highlights the growing literature on the use of DOT in the study of healthy
development of the infant brain, and the study of novel pathophysiology in
infants with brain injury. Current challenges, particularly around
instrumentation and image reconstruction, will be discussed, as will the future
of this growing field, with particular focus on whole-brain, time-resolved DOT.
PMID- 28419083
TI - Pneumococcal vaccination and efficacy in patients with heterotaxy syndrome.
AB - BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine
(PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing
invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate,
efficacy, and durability in patients with heterotaxy.MethodsAll patients with
heterotaxy and CCHD who were followed up at our institution between 2010 and 2015
were included. Pneumococcal vaccine status and geometric mean concentration (GMC)
of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered
abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe
GMCs of the four serotypes did not differ significantly between patients with
heterotaxy and those with CCHD; the GMCs were also not affected by abnormal
splenic function. Most patients had GMCs >0.35 MUg/ml (protection level) 4-5
years after either PPV or PCV injection; however, it may decay gradually in some
serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive
pneumococcal vaccine, and none completely adhered to the vaccine
guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with
abnormal splenic function. In some patients, the durability of PPV and PCV
decreased with time, highlighting the importance of booster doses. Vaccination
rate in patients with heterotaxy is unsatisfactory.
PMID- 28419084
TI - Neonatal resuscitation in global health settings: an examination of the past to
prepare for the future.
AB - As rates of childhood mortality decline, neonatal deaths account for nearly half
of under-5 deaths worldwide. Intrapartum-related events (birth asphyxia)
contribute to approximately one-quarter of neonatal deaths, many of which can be
prevented by simple resuscitation and newborn care interventions. This paper
reviews various lines of research that have influenced the global neonatal
resuscitation landscape. A brief situational analysis of asphyxia-related newborn
mortality in low-resource settings is linked to renewed efforts to reduce
neonatal mortality in the Every Newborn Action Plan. Possible solutions to gaps
in care are identified. Building on international scientific evidence, tests of
educational efficacy, and community-based trials established the feasibility and
effectiveness of training in resource-limited settings and identified successful
implementation strategies. Implementation of neonatal resuscitation programs has
been shown to decrease intrapartum stillbirth rates and early neonatal mortality.
Challenges remain with respect to provider competencies, coverage, and quality of
interventions. The combination of resuscitation science, strategies to increase
educational effectiveness, and implemention of interventions with high coverage
and quality has resulted in reduced rates of asphyxia-related neonatal mortality.
Further efforts to improve coverage and implementation of neonatal resuscitation
will be necessary to meet the 2035 goal of eliminating preventable newborn
deaths.
PMID- 28419085
TI - Neonatal outcomes of moderately preterm infants compared to extremely preterm
infants.
AB - BackgroundExtremely preterm infants (EPT, <29 weeks' gestation) represent only
0.9% of births in the United States; yet these infants are the focus of most
published research. Moderately preterm neonates (MPT, 29-336/7 weeks) are an
understudied group of high-risk infants.MethodsTo determine the neonatal outcomes
of MPT infants across the gestational age spectrum, and to compare these with EPT
infants. A prospective observational cohort was formed in 18 level 3-4 neonatal
intensive care units (NICUs) in the Eunice Kennedy Shriver NICHD Neonatal
Research Network. Participants included all MPT infants admitted to NICUs and all
EPT infants born at sites between January 2012 and November 2013. Antenatal
characteristics and neonatal morbidities were abstracted from records using pre
specified definitions by trained neonatal research nurses.ResultsMPT infants
experienced morbidities similar to, although at lower rates than, those of EPT
infants. The main cause of mortality was congenital malformation, accounting for
43% of deaths. Central Nervous System injury occurred, including intraventricular
hemorrhage. Most MPT infants required respiratory support, but sequelae such as
bronchopulmonary dysplasia were rare. The primary contributors to hospitalization
beyond 36 weeks' gestation were inability to achieve adequate oral intake and
persistent apnea.ConclusionsMPT infants experience morbidity and prolonged
hospitalization. Such morbidity deserves focused research to improve therapeutic
and prevention strategies.
PMID- 28419086
TI - Low birth weight is associated with impaired murine kidney development and
function.
AB - BackgroundLow birth weight (LBW) neonates have impaired kidney development that
leaves them susceptible to kidney disease and hypertension during adulthood. The
study here identifies events that blunt nephrogenesis and kidney development in
the murine LBW neonate.MethodsWe examined survival, kidney development, GFR, gene
expression, and cyto-/chemokines in the LBW offspring of malnourished (caloric
and protein-restricted) pregnant mice.ResultsMalnourished pregnant mothers gave
birth to LBW neonates that had 40% reduced body weight and 54% decreased
survival. Renal blood perfusion was reduced by 37%, whereas kidney volume and GFR
were diminished in the LBW neonate. During gestation, the LBW neonatal kidney had
2.2-fold increased apoptosis, 76% decreased SIX2+ progenitor cells,
downregulation of mesenchymal-to-epithelial signaling factors Wnt9b and Fgf8, 64%
less renal vesicle formation, and 32% fewer nephrons than controls. At birth,
increased plasma levels of IL-1beta, IL-6, IL-12(p70), and granulocyte-macrophage
colony-stimulating factor in the LBW neonate reduced SIX2+ progenitor
cells.ConclusionIncreased pro-inflammatory cytokines in the LBW neonate decrease
SIX2+ stem cells in the developing kidney. Reduced renal stem cells (along with
the decreased mesenchymal-to-epithelial signaling) blunt renal vesicle
generation, nephron formation, and kidney development. Subsequently, the mouse
LBW neonate has reduced glomeruli volume, renal perfusion, and GFR.
PMID- 28419087
TI - Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA.
AB - BackgroundNeuroblastoma is the second most common extracranial cancer in
children. Current therapies for neuroblastoma, which use a combination of
chemotherapy drugs, have limitations for high-risk subtypes and can cause
significant long-term adverse effects in young patients. Therefore, a new therapy
is needed. In this study, we investigated the transcription factor MXD3 as a
potential therapeutic target in neuroblastoma.MethodsMXD3 expression was analyzed
in five neuroblastoma cell lines by immunocytochemistry and quantitative real
time reverse transcription PCR, and in 18 primary patient tumor samples by
immunohistochemistry. We developed nanocomplexes using siRNA and
superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell
lines in vitro as a single-agent therapeutic and in combination with doxorubicin,
vincristine, cisplatin, or maphosphamide-common drugs used in current
neuroblastoma treatment.ResultsMXD3 was highly expressed in neuroblastoma cell
lines and in patient tumors that had high-risk features. Neuroblastoma cells
treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown
and resulted in cell apoptosis. Furthermore, on combining MXD3 siRNA
nanocomplexes with each of the four drugs, all showed additive
efficacy.ConclusionThese results indicate that MXD3 is a potential new target and
that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for
neuroblastoma.
PMID- 28419088
TI - The SnRK2 kinases modulate miRNA accumulation in Arabidopsis.
AB - MicroRNAs (miRNAs) regulate gene expression and play critical roles in growth and
development as well as stress responses in eukaryotes. miRNA biogenesis in plants
requires a processing complex that consists of the core components DICER-LIKE 1
(DCL1), SERRATE (SE) and HYPONASTIC LEAVES (HYL1). Here we show that inactivation
of functionally redundant members of the SnRK2 kinases, which are the core
components of abscisic acid (ABA) and osmotic stress signaling pathways, leads to
reduction in miRNA accumulation under stress conditions. Further analysis
revealed that the steady state level of HYL1 protein in plants under osmotic
stress is dependent on the SnRK2 kinases. Additionally, our results suggest that
the SnRK2 kinases physically associate with the miRNA processing components SE
and HYL1 and can phosphorylate these proteins in vitro. These findings reveal an
important role for the SnRK2 kinases in the regulation of miRNA accumulation and
establish a mechanism by which ABA and osmotic stress signaling is linked to
miRNA biogenesis.
PMID- 28419089
TI - Erroneous energy-generating cycles in published genome scale metabolic networks:
Identification and removal.
AB - Energy metabolism is central to cellular biology. Thus, genome-scale models of
heterotrophic unicellular species must account appropriately for the utilization
of external nutrients to synthesize energy metabolites such as ATP. However,
metabolic models designed for flux-balance analysis (FBA) may contain
thermodynamically impossible energy-generating cycles: without nutrient
consumption, these models are still capable of charging energy metabolites (such
as ADP->ATP or NADP+->NADPH). Here, we show that energy-generating cycles occur
in over 85% of metabolic models without extensive manual curation, such as those
contained in the ModelSEED and MetaNetX databases; in contrast, such cycles are
rare in the manually curated models of the BiGG database. Energy generating
cycles may represent model errors, e.g., erroneous assumptions on reaction
reversibilities. Alternatively, part of the cycle may be thermodynamically
feasible in one environment, while the remainder is thermodynamically feasible in
another environment; as standard FBA does not account for thermodynamics,
combining these into an FBA model allows erroneous energy generation. The
presence of energy-generating cycles typically inflates maximal biomass
production rates by 25%, and may lead to biases in evolutionary simulations. We
present efficient computational methods (i) to identify energy generating cycles,
using FBA, and (ii) to identify minimal sets of model changes that eliminate
them, using a variant of the GlobalFit algorithm.
PMID- 28419090
TI - The co-existence of transcriptional activator and transcriptional repressor MEF2
complexes influences tumor aggressiveness.
AB - The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here
we clarify that MEF2 can support both pro-oncogenic or tumor suppressive
activities depending on the interaction with co-activators or co-repressors
partners. Through these interactions MEF2 supervise histone modifications
associated with gene activation/repression, such as H3K4 methylation and H3K27
acetylation. Critical switches for the generation of a MEF2 repressive
environment are class IIa HDACs. In leiomyosarcomas (LMS), this two-faced trait
of MEF2 is relevant for tumor aggressiveness. Class IIa HDACs are overexpressed
in 22% of LMS, where high levels of MEF2, HDAC4 and HDAC9 inversely correlate
with overall survival. The knock out of HDAC9 suppresses the transformed
phenotype of LMS cells, by restoring the transcriptional proficiency of some MEF2
target loci. HDAC9 coordinates also the demethylation of H3K4me3 at the promoters
of MEF2-target genes. Moreover, we show that class IIa HDACs do not bind all the
regulative elements bound by MEF2. Hence, in a cell MEF2-target genes actively
transcribed and strongly repressed can coexist. However, these repressed MEF2
targets are poised in terms of chromatin signature. Overall our results candidate
class IIa HDACs and HDAC9 in particular, as druggable targets for a therapeutic
intervention in LMS.
PMID- 28419091
TI - Multidrug-resistant bacteria compensate for the epistasis between resistances.
AB - Mutations conferring resistance to antibiotics are typically costly in the
absence of the drug, but bacteria can reduce this cost by acquiring compensatory
mutations. Thus, the rate of acquisition of compensatory mutations and their
effects are key for the maintenance and dissemination of antibiotic resistances.
While compensation for single resistances has been extensively studied,
compensatory evolution of multiresistant bacteria remains unexplored.
Importantly, since resistance mutations often interact epistatically,
compensation of multiresistant bacteria may significantly differ from that of
single-resistant strains. We used experimental evolution, next-generation
sequencing, in silico simulations, and genome editing to compare the compensatory
process of a streptomycin and rifampicin double-resistant Escherichia coli with
those of single-resistant clones. We demonstrate that low-fitness double
resistant bacteria compensate faster than single-resistant strains due to the
acquisition of compensatory mutations with larger effects. Strikingly, we
identified mutations that only compensate for double resistance, being neutral or
deleterious in sensitive or single-resistant backgrounds. Moreover, we show that
their beneficial effects strongly decrease or disappear in conditions where the
epistatic interaction between resistance alleles is absent, demonstrating that
these mutations compensate for the epistasis. In summary, our data indicate that
epistatic interactions between antibiotic resistances, leading to large fitness
costs, possibly open alternative paths for rapid compensatory evolution, thereby
potentially stabilizing costly multiple resistances in bacterial populations.
PMID- 28419092
TI - A multi-centric Study of Candida bloodstream infection in Lima-Callao, Peru:
Species distribution, antifungal resistance and clinical outcomes.
AB - BACKGROUND: The incidence of candidemia is increasing in developing countries.
Very little is known about the epidemiology of candidemia in Peru. The aim of
this study is to describe the incidence, microbiology, clinical presentation and
outcomes of Candida bloodstream infections in three Lima-Callao hospitals.
METHODS: Candida spp. isolates were identified prospectively at participant
hospitals between November 2013 and January 2015. Susceptibility testing for
amphotericin B, fluconazole, posaconazole, voriconazole and anidulafungin was
performed using broth microdilution method. Clinical information was obtained
from medical records and evaluated. RESULTS: We collected information on 158
isolates and 157 patients. Median age of patients was 55.0 yrs., and 64.1% were
males. Thirty-eight (24.2%) episodes of candidemia occurred in those <18 yrs. The
frequency of non-Candida albicans was 72.1%. The most frequently recovered
species were C. albicans (n = 44, 27.8%), C. parapsilosis (n = 40, 25.3%), C.
tropicalis (n = 39, 24.7%) and C. glabrata (n = 15, 9.5%). Only four isolates
were resistant to fluconazole, 86.7% (n = 137) were susceptible and 17 were
susceptible-dose dependent. Decreased susceptibility to posaconazole was also
observed in three isolates, and one to voriconazole. All isolates were
susceptible to anidulafungin and amphotericin B. The most commonly associated co
morbid conditions were recent surgery (n = 61, 38.9%), mechanical ventilation (n
= 60, 38.2%) and total parenteral nutrition (n = 57, 36.3%). The incidence of
candidemia by center ranged between 1.01 and 2.63 cases per 1,000 admissions,
with a global incidence of 2.04. Only 28.1% of cases received treatment within 72
hrs. of diagnosis. Overall, the 30-day survival was 60.4% (treated subjects,
67.4%; not-treated patients, 50.9%). CONCLUSIONS: We found a very high proportion
of non-albicans Candida species. Despite this, the decreased
susceptibility/resistance to fluconazole was only 13.3% and not seen in the other
antifungals. Overall, the incidence of candidemia mortality was high when
compared to other international studies. It is possible, that the delay in
initiating antifungal treatment contributed to the elevated mortality rate, in
spite of low antifungal resistance.
PMID- 28419093
TI - Microhomology-mediated end joining induces hypermutagenesis at breakpoint
junctions.
AB - Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal
rearrangements but its role in mutagenesis has not yet been analyzed. Here we
determined the mutation frequency of a URA3 reporter gene placed at multiple
locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203
bp) of direct repeat sequences for efficient repair in budding yeast. Induction
of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal
to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no
homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled
to its slower repair kinetics and the extensive resection occurring at flanking
DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking
DNA sequences 7.1 kb distal to the breakpoint junction as compared to those
without MH. The results suggest that MMEJ could destabilize genomes by triggering
structural alterations and increasing mutation burden.
PMID- 28419094
TI - An open source pharma roadmap.
AB - In an Essay, Matthew Todd and colleagues discuss an open source approach to drug
development.
PMID- 28419096
TI - Determinants of neonatal mortality in rural Northern Ethiopia: A population based
nested case control study.
AB - INTRODUCTION: In low income and middle income countries, neonatal mortality
remains high despite the gradual reduction in under five mortality. Newborn death
contributes for about 38% of all under five deaths. This study has identified the
magnitude and independent predictors of neonatal mortality in rural Ethiopia.
METHODS: This population based nested case control study was conducted in rural
West Gojam zone, Northern Ethiopia, among a cohort of pregnant women who gave
birth between March 2011 and Feb 2012. The cohort was established by Maternal and
Newborn Health in Ethiopia Partnership (MaNHEP) project in 2010 by recruiting
mothers in their third trimester, as identified by trained community volunteers.
Once identified, women stayed in the cohort throughout their pregnancy period
receiving Community Maternal and Newborn Health (CMNH) training by health
extension workers and community volunteers till the end of the first 48 hours
postpartum. Cases were 75 mothers who lost their newborns to neonatal death and
controls were 150 randomly selected mothers with neonates who survived the
neonatal period. Data to identify cause of death were collected using the WHO
standard verbal autopsy questionnaire after the culturally appropriate 40 days of
bereavement period. Binomial logistic regression model was used to identify
independent contributors to neonatal mortality. RESULT: The neonatal mortality
rate was AOR(95%CI) = 18.6 (14.8, 23.2) per 1000 live births. Neonatal mortality
declined with an increase in family size, neonates who were born among a family
of more than two had lesser odds of death in the neonatal period than those who
were born in a family of two AOR (95% CI) = 0.13 (0.02, 0.71). Mothers who gave
birth to 2-4 AOR(95%CI) = 0.15 (0.05, 0.48) and 5+ children AOR(95%CI) = 0.08
(0.02, 0.26) had lesser odds of losing their newborns to neonatal mortality.
Previous history of losing a newborn to neonatal death also increased the odds of
neonatal mortality during the last birth AOR (95%CI) = 0.25 (0.11, 0.53).
CONCLUSION: The neonatal mortality rate in our study was three times lower than
the regional neonatal mortality rate estimate, indicating community based
interventions could significantly decrease neonatal mortality. The identified
determinants, which are amenable for change, emphasize the need to improve
quality of care during pregnancy, labour and delivery to improve pregnancy
outcome.
PMID- 28419095
TI - Effectiveness of a live oral human rotavirus vaccine after programmatic
introduction in Bangladesh: A cluster-randomized trial.
AB - BACKGROUND: Rotavirus vaccines are now globally recommended by the World Health
Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts
on Immunization reviewed available data and concluded that there was no evidence
for the efficacy or effectiveness of a two-dose schedule of the human rotavirus
vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the
effectiveness of programmatic rotavirus vaccination, including possible indirect
effects, has not been assessed in low-resource populations in Asia. METHODS AND
FINDINGS: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab
Health and Demographic Surveillance System to include two doses of HRV with the
standard infant vaccines at 6 and 10 wk of age or to provide standard infant
vaccines without HRV. The study was initiated November 1, 2008, and surveillance
was conducted concurrently at Matlab Diarrhoea Hospital and two community
treatment centers to identify children less than 2 y of age presenting with acute
rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made
by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall
effectiveness of the HRV vaccination program (primary objective) was measured by
comparing the incidence rate of ARD among all children age-eligible for
vaccination in villages where HRV was introduced to that among such children in
villages where HRV was not introduced. Total effectiveness among vaccinees and
indirect effectiveness were also evaluated. In all, 6,527 infants were age
eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In
HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The
incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages
compared to 2.8 per 100 person-years in HRV villages, indicating an overall
effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV
against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point
estimate for total effectiveness was higher against ARD during the first year of
life than during the second (45.2% versus 28.9%), but estimates for the second
year of life lacked precision and did not reach statistical significance.
Indirect effects were not detected. To check for bias in presentation to
treatment facilities, we evaluated the effectiveness of HRV against acute
diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI,
46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious
adverse events were identified among recipients of HRV, but none were considered
related to receipt of study vaccine. The main limitation of this study is that it
was an open-label study with an observed-only control group (no placebo).
CONCLUSIONS: The two-dose HRV rotavirus vaccination program significantly reduced
medically attended ARD in this low-resource population in Asia. Protection among
vaccinees was similar to that in other low-resource settings. In low-resource
populations with high rotavirus incidence, large-scale vaccination across a wide
population may be required to obtain the full benefit of rotavirus vaccination,
including indirect effects. TRIAL REGISTRATION: ClinicalTrials.gov NCT00737503.
PMID- 28419097
TI - Clinical decision tools are needed to identify HIV-positive patients at high risk
for poor outcomes after initiation of antiretroviral therapy.
AB - Margaret McNairy and colleagues highlight the need for clinical decision tools to
help identify HIV patients who would benefit from tailored services to avoid poor
outcomes such as death and loss to follow-up.
PMID- 28419098
TI - Robust information propagation through noisy neural circuits.
AB - Sensory neurons give highly variable responses to stimulation, which can limit
the amount of stimulus information available to downstream circuits. Much work
has investigated the factors that affect the amount of information encoded in
these population responses, leading to insights about the role of covariability
among neurons, tuning curve shape, etc. However, the informativeness of neural
responses is not the only relevant feature of population codes; of potentially
equal importance is how robustly that information propagates to downstream
structures. For instance, to quantify the retina's performance, one must consider
not only the informativeness of the optic nerve responses, but also the amount of
information that survives the spike-generating nonlinearity and noise corruption
in the next stage of processing, the lateral geniculate nucleus. Our study
identifies the set of covariance structures for the upstream cells that optimize
the ability of information to propagate through noisy, nonlinear circuits. Within
this optimal family are covariances with "differential correlations", which are
known to reduce the information encoded in neural population activities. Thus,
covariance structures that maximize information in neural population codes, and
those that maximize the ability of this information to propagate, can be very
different. Moreover, redundancy is neither necessary nor sufficient to make
population codes robust against corruption by noise: redundant codes can be very
fragile, and synergistic codes can-in some cases-optimize robustness against
noise.
PMID- 28419099
TI - Getting ready to use control: Advances in the measurement of young children's use
of proactive control.
AB - A key developmental transition in executive function is in the temporal dynamics
of its engagement: children shift from reactively calling to mind task-relevant
information as needed, to being able to proactively maintain information across
time in anticipation of upcoming demands. This transition is important for
understanding individual differences and developmental changes in executive
function; however, methods targeting its assessment are limited. We tested the
possibility that Track-It, a paradigm developed to measure selective sustained
attention, also indexes proactive control. In this task children must track a
target shape as it moves unpredictably among moving distractors, and identify
where it disappears, which may require proactively maintaining information about
the target or goal. In two experiments (5-6 year-olds, Ns = 33, 64), children's
performance on Track-It predicted proactive control across two established
paradigms. These findings suggest Track-It measures proactive control in
children. Theoretical possibilities regarding how proactive control and selective
sustained attention may be related are also discussed.
PMID- 28419100
TI - Validation of two multiplex platforms to quantify circulating markers of
inflammation and endothelial injury in severe infection.
AB - Biomarkers can prognosticate outcome and enable risk-stratification. In severe
infection, focusing on multiple markers reflecting pathophysiological mechanisms
of organ injury could enhance management and pathway-directed therapeutics.
Limited data exist on the performance of multiplex biomarker platforms. Our goal
was to compare endothelial and immune activation biomarkers in severe pediatric
infections using two multiplex platforms. Frozen plasma from 410 children
presenting to the Jinja Regional Hospital in Uganda with suspected infection was
used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1, sICAM
1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex platforms
(Luminex(r), EllaTM) based on monoclonal antibody sandwich immunoassays using
biotin-streptavidin conjugate chemistry were selected with reagents from R&D
Systems. The two platforms differed in ease and time of completion, number of
samples per assay, and dynamic concentration range. Intra-assay variability
assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex(r) and
1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic
range of both platforms were best for IL-6 (rho = 0.96, p<0.0001), IP-10 (rho =
0.94, p<0.0001) and sFlt-1 (rho = 0.94, p<0.0001). Agreement between
concentrations obtained by both methods assessed by the Bland-Altman test varied,
with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial
and immune activation can be readily measured with multiplex platforms.
Luminex(r) and EllaTM produced reliable results with excellent CV% values. The
EllaTM platform was more automated and completed in 75 minutes, potentially
compatible with near-patient use. Trends in concentrations obtained by these
methods were highly correlated, although absolute values varied, suggesting
caution is required when comparing data from different multiplex platforms.
PMID- 28419101
TI - Anti-proliferative effect of novel primary cetyl alcohol derived sophorolipids
against human cervical cancer cells HeLa.
AB - Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display
anticancer activity. In the present study, we report anti-proliferative studies
on purified forms of novel SLs synthesized using cetyl alcohol as the substrate
(referred as SLCA) and their anticancer mechanism in human cervical cancer cells.
Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F)
was examined in panel of human cancer cell lines as well as primary cells. Among
these fractions, SLCA B and C significantly inhibited the survival of HeLa and
HCT 116 cells without affecting the viability of normal human umbilical vein
endothelial cells (HUVEC). The two fractions were identified as cetyl alcohol
sophorolipids with non-hydroxylated tail differing in the degree of acetylation
on sophorose head group. At an IC50 concentration SLCA B (16.32 MUg ml-1) and
SLCA C (14.14 MUg ml-1) blocked the cell cycle progression of HeLa cells at G1/S
phase in time-dependent manner. Moreover, SLCA B and SLCA C induced apoptosis in
HeLa cells through an increase in intracellular Ca2+ leading to depolarization of
mitochondrial membrane potential and increase in the caspase-3, -8 and -9
activity. All these findings suggest that these SLCAs could be explored for their
chemopreventive potential in cervical cancer.
PMID- 28419102
TI - Effect of genomic distance on coexpression of coregulated genes in E. coli.
AB - In prokaryotes, genomic distance is a feature that in addition to coregulation
affects coexpression. Several observations, such as genomic clustering of highly
coexpressed small regulons, support the idea that coexpression behavior of
coregulated genes is affected by the distance between the coregulated genes.
However, the specific contribution of distance in addition to coregulation in
determining the degree of coexpression has not yet been studied systematically.
In this work, we exploit the rich information in RegulonDB to study how the
genomic distance between coregulated genes affects their degree of coexpression,
measured by pairwise similarity of expression profiles obtained under a large
number of conditions. We observed that, in general, coregulated genes display
higher degrees of coexpression as they are more closely located on the genome.
This contribution of genomic distance in determining the degree of coexpression
was relatively small compared to the degree of coexpression that was determined
by the tightness of the coregulation (degree of overlap of regulatory programs)
but was shown to be evolutionary constrained. In addition, the distance effect
was sufficient to guarantee coexpression of coregulated genes that are located at
very short distances, irrespective of their tightness of coregulation. This is
partly but definitely not always because the close distance is also the cause of
the coregulation. In cases where it is not, we hypothesize that the effect of the
distance on coexpression could be caused by the fact that coregulated genes
closely located to each other are also relatively more equidistantly located from
their common TF and therefore subject to more similar levels of TF molecules. The
absolute genomic distance of the coregulated genes to their common TF-coding gene
tends to be less important in determining the degree of coexpression. Our results
pinpoint the importance of taking into account the combined effect of distance
and coregulation when studying prokaryotic coexpression and transcriptional
regulation.
PMID- 28419103
TI - Establishment of a tear protein biomarker panel differentiating between Graves'
disease with or without orbitopathy.
AB - BACKGROUND: Graves' orbitopathy (GO) is an autoimmune inflammatory ocular
complication and one of the most frequent manifestations of Graves' disease (GD).
Clinical judgment of GO is subjective sometimes leading to clinical and
therapeutic challenges. Better tools to diagnose this severe complication are
warranted. PATIENTS AND METHODS: The aim of the present study was to evaluate
tear levels of LYZ, LACRT and AZGP1 in GD patients with or without GO, as
possible biomarkers for GO. Tear samples were collected from GD patients with
moderate-to-severe GO (n = 21) and no clinical signs of GO (n = 21).
Additionally, 18 GD patients with mild GO and 9 patients without GO were included
in a further part of the study. RESULTS: Tear levels of LYZ (p < 0.001), LACRT (p
= 0.004) and AZGP1 (p = 0.001) were significantly elevated in GD patients with
moderate-to-severe GO compared to GD patients without GO. The discriminatory
power of the three biomarkers, combined in a panel was confirmed by ROC plot
analysis, with an AUC value of 0.93 (sensitivity of 95%; specificity of 80%).
Since LYZ showed the best performance in discriminating between GD patients with
(moderate-to-severe) and without GO (in combination with limited sample volume
available), LYZ levels were also measured in tears from GD patients with mild GO
and without GO. Significantly higher levels of LYZ were measured in GD patients
with mild GO compared to those without GO (p = 0.003). CONCLUSIONS: We have
established a novel three-protein biomarker panel that is able to discriminate
between GD patients with and without GO, which might aid in diagnostic evaluation
of GO as well as an indicator for disease activity.
PMID- 28419104
TI - Further characterisation of differences between TL and AB zebrafish (Danio
rerio): Gene expression, physiology and behaviour at day 5 of the larval stage.
AB - Zebrafish (Danio rerio) have become popular as model organism in research. Many
strains are readily available, which not only differ morphologically, but also
genetically, physiologically and behaviourally. Here, we focus on the AB and
Tupfel long-fin (TL) strain for which we have previously shown that adults differ
in baseline hypothalamus-pituitary-interrenal (HPI)-axis activity (AB higher than
TL) affecting inhibitory avoidance behaviour (absent in AB). To assess whether
strain differences are already present in early life stages, we compared baseline
HPI-axis related gene expression as well as cortisol levels, (neuro)development
related as well as (innate) immune system related gene expression, and light-dark
as well as startle behaviour in larvae 5 days post fertilisation. The data show
that AB and TL larvae differ in baseline HPI-axis activity (AB higher than TL),
expression of (neuro)development and immune system related genes (AB higher than
TL), habituation to acoustic/vibrational stimuli (AB habituate faster than TL)
and light-dark induced changes in motor behaviour (AB stronger than TL). Our data
show that already in larval stages differences exist between zebrafish of the AB
and TL strain confirming and extending data of earlier studies. To what extent
the mutation in connexin 41.8, leading to spots rather than stripes in TL, but
also (possibly) affecting eye, heart and brain function, is involved in the
expression of (some of) these differences needs to be studied. These results
emphasise that differences between strains need to be taken into account to
enhance reproducibility both within, and between, laboratories.
PMID- 28419105
TI - Year-round breeding equatorial Larks from three climatically-distinct populations
do not use rainfall, temperature or invertebrate biomass to time reproduction.
AB - Timing of reproduction in birds is important for reproductive success and is
known to depend on environmental cues such as day length and food availability.
However, in equatorial regions, where day length is nearly constant, other
factors such as rainfall and temperature are thought to determine timing of
reproduction. Rainfall can vary at small spatial and temporal scales, providing a
highly fluctuating and unpredictable environmental cue. In this study we
investigated the extent to which spatio-temporal variation in environmental
conditions can explain the timing of breeding of Red-capped Lark, Calandrella
cinerea, a species that is capable of reproducing during every month of the year
in our equatorial east African study locations. For 39 months in three
climatically-distinct locations, we monitored nesting activities, sampled ground
and flying invertebrates, and quantified rainfall, maximum (Tmax) and minimum
(Tmin) temperatures. Among locations we found that lower rainfall and higher
temperatures did not coincide with lower invertebrate biomasses and decreased
nesting activities, as predicted. Within locations, we found that rainfall, Tmax,
and Tmin varied unpredictably among months and years. The only consistent
annually recurring observations in all locations were that January and February
had low rainfall, high Tmax, and low Tmin. Ground and flying invertebrate
biomasses varied unpredictably among months and years, but invertebrates were
captured in all months in all locations. Red-capped Larks bred in all calendar
months overall but not in every month in every year in every location. Using
model selection, we found no clear support for any relationship between the
environmental variables and breeding in any of the three locations. Contrary to
popular understanding, this study suggests that rainfall and invertebrate biomass
as proxy for food do not influence breeding in equatorial Larks. Instead, we
propose that factors such as nest predation, female protein reserves, and
competition are more important in environments where weather and food meet
minimum requirements for breeding during most of the year.
PMID- 28419106
TI - Quality improvement intervention to increase adherence to ART prescription policy
at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.
AB - INTRODUCTION: In urban areas, crowded HIV treatment facilities with long patient
wait times can deter patients from attending their clinical appointments and
picking up their medications, ultimately disrupting patient care and compromising
patient retention and adherence. METHODS: Formative research at eight facilities
in Lusaka revealed that only 46% of stable HIV treatment patients were receiving
a three-month refill supply of antiretroviral drugs, despite it being national
policy for stable adult patients. We designed a quality improvement intervention
to improve the operationalization of this policy. We conducted a cluster
randomized controlled trial in sixteen facilities in Lusaka with the primary
objective of examining the intervention's impact on the proportion of stable
patients receiving three-month refills. The secondary objective was examining
whether the quality improvement intervention reduced facility congestion measured
through two proxy indicators: daily volume of clinic visits and average clinic
wait times for services. RESULTS: The mean change in the proportion of three
month refills among control facilities from baseline to endline was 10% (from 38%
to 48%), compared to a 25% mean change (an increase from 44% to 69%) among
intervention facilities. This represents a significant 15% mean difference (95%
CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three
month refills. On average, control facilities had 15 more visits per day in the
endline than in the baseline, while intervention facilities had 20 fewer visits
per day in endline than in baseline, a mean difference of 35 fewer visits per day
(P = 0.1). The change in the mean facility total wait time for intervention
facilities dropped 19 minutes between baseline and endline when compared to
control facilities (95% CI: -10.2-48.5; P = 0.2). CONCLUSION: A more patient
centred service delivery schedule of three-month prescription refills for stable
patients is viable. We encourage the expansion of this sustainable intervention
in Zambia's urban clinics.
PMID- 28419107
TI - Characterization of a transgenic mouse model exhibiting spontaneous lung
adenocarcinomas with a metastatic phenotype.
AB - Developing lung cancer in mouse models that display similarities of both
phenotype and genotype will undoubtedly provide further and better insights into
lung tumor biology. Moreover, a high degree of pathophysiological similarity
between lung tumors from mouse models and their human counterparts will make it
possible to use these mouse models for preclinical tests. Ovine pulmonary
adenocarcinomas (OPAs) present the same symptoms as adenocarcinomas in humans and
are caused by a betaretrovirus. OPAs have served as an exquisite model of
carcinogenesis for human lung adenocarcinomas. In this study, we characterized
the histopathology and transcriptome profiles of a jaagsiekte sheep retrovirus
(JSRV)-envelope protein (Env) transgenic mouse model with spontaneous lung
tumors, and associations of the transcriptome profiles with tumor
invasion/metastasis, especially the phenomenon of the epithelial-mesenchymal
transition (EMT). Genetic information obtained from an expression array was
analyzed using an ingenuity pathways analysis (IPA) and human disease database
(MalaCards). By careful examination, several novel EMT-related genes were
identified from tumor cells using RT-qPCR, and these genes also scored high in
MalaCards. We concluded that the JSRV-Env mouse model could serve as a
spontaneous lung adenocarcinoma model with a metastatic phenotype, which will
benefit the study of early-onset and progression of lung adenocarcinoma. In
addition, it can also be a valuable tool for biomarkers and drug screening, which
will be helpful in developing intervention therapies.
PMID- 28419108
TI - Changes in prices, sales, consumer spending, and beverage consumption one year
after a tax on sugar-sweetened beverages in Berkeley, California, US: A before
and-after study.
AB - BACKGROUND: Taxes on sugar-sweetened beverages (SSBs) meant to improve health and
raise revenue are being adopted, yet evaluation is scarce. This study examines
the association of the first penny per ounce SSB excise tax in the United States,
in Berkeley, California, with beverage prices, sales, store revenue/consumer
spending, and usual beverage intake. METHODS AND FINDINGS: Methods included
comparison of pre-taxation (before 1 January 2015) and first-year post-taxation
(1 March 2015-29 February 2016) measures of (1) beverage prices at 26 Berkeley
stores; (2) point-of-sale scanner data on 15.5 million checkouts for beverage
prices, sales, and store revenue for two supermarket chains covering three
Berkeley and six control non-Berkeley large supermarkets in adjacent cities; and
(3) a representative telephone survey (17.4% cooperation rate) of 957 adult
Berkeley residents. Key hypotheses were that (1) the tax would be passed through
to the prices of taxed beverages among the chain stores in which Berkeley
implemented the tax in 2015; (2) sales of taxed beverages would decline, and
sales of untaxed beverages would rise, in Berkeley stores more than in comparison
non-Berkeley stores; (3) consumer spending per transaction (checkout episode)
would not increase in Berkeley stores; and (4) self-reported consumption of taxed
beverages would decline. Main outcomes and measures included changes in inflation
adjusted prices (cents/ounce), beverage sales (ounces), consumers' spending
measured as store revenue (inflation-adjusted dollars per transaction) in two
large chains, and usual beverage intake (grams/day and kilocalories/day). Tax
pass-through (changes in the price after imposition of the tax) for SSBs varied
in degree and timing by store type and beverage type. Pass-through was complete
in large chain supermarkets (+1.07c/oz, p = 0.001) and small chain supermarkets
and chain gas stations (1.31c/oz, p = 0.004), partial in pharmacies (+0.45c/oz, p
= 0.03), and negative in independent corner stores and independent gas stations (
0.64c/oz, p = 0.004). Sales-unweighted mean price change from scanner data was
+0.67c/oz (p = 0.00) (sales-weighted, +0.65c/oz, p = 0.003), with +1.09c/oz (p <
0.001) for sodas and energy drinks, but a lower change in other categories. Post
tax year 1 scanner data SSB sales (ounces/transaction) in Berkeley stores
declined 9.6% (p < 0.001) compared to estimates if the tax were not in place, but
rose 6.9% (p < 0.001) for non-Berkeley stores. Sales of untaxed beverages in
Berkeley stores rose by 3.5% versus 0.5% (both p < 0.001) for non-Berkeley
stores. Overall beverage sales also rose across stores. In Berkeley, sales of
water rose by 15.6% (p < 0.001) (exceeding the decline in SSB sales in ounces);
untaxed fruit, vegetable, and tea drinks, by 4.37% (p < 0.001); and plain milk,
by 0.63% (p = 0.01). Scanner data mean store revenue/consumer spending (dollars
per transaction) fell 18c less in Berkeley (-$0.36, p < 0.001) than in comparison
stores (-$0.54, p < 0.001). Baseline and post-tax Berkeley SSB sales and usual
dietary intake were markedly low compared to national levels (at baseline,
National Health and Nutrition Examination Survey SSB intake nationally was 131
kcal/d and in Berkeley was 45 kcal/d). Reductions in self-reported mean daily SSB
intake in grams (-19.8%, p = 0.49) and in mean per capita SSB caloric intake (
13.3%, p = 0.56) from baseline to post-tax were not statistically significant.
Limitations of the study include inability to establish causal links due to
observational design, and the absence of health outcomes. Analysis of consumption
was limited by the small effect size in relation to high standard error and
Berkeley's low baseline consumption. CONCLUSIONS: One year following
implementation of the nation's first large SSB tax, prices of SSBs increased in
many, but not all, settings, SSB sales declined, and sales of untaxed beverages
(especially water) and overall study beverages rose in Berkeley; overall consumer
spending per transaction in the stores studied did not rise. Price increases for
SSBs in two distinct data sources, their timing, and the patterns of change in
taxed and untaxed beverage sales suggest that the observed changes may be
attributable to the tax. Post-tax self-reported SSB intake did not change
significantly compared to baseline. Significant declines in SSB sales, even in
this relatively affluent community, accompanied by revenue used for prevention
suggest promise for this policy. Evaluation of taxation in jurisdictions with
more typical SSB consumption, with controls, is needed to assess broader dietary
and potential health impacts.
PMID- 28419109
TI - Polymorphisms in the selectin gene cluster are associated with fertility and
survival time in a population of Holstein Friesian cows.
AB - Selectins are adhesion molecules, which mediate attachment between leucocytes and
endothelium. They aid extravasation of leucocytes from blood into inflamed tissue
during the mammary gland's response to infection. Selectins are also involved in
attachment of the conceptus to the endometrium and subsequent placental
development. Poor fertility and udder health are major causes for culling dairy
cows. The three identified bovine selectin genes SELP, SELL and SELE are located
in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in
SELP and SELE are associated with human vascular disease, while SELP SNP rs6127
has been associated with recurrent pregnancy loss in women. This study describes
the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and
SELE (n = 1) with fertility, milk production and longevity traits in a population
of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at
6 months of age and animals were monitored until either culling or 2,340 days
from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala
substitution at rs42312260. This region was associated with poor fertility and
reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus
in the linking region between consensus repeats 4 and 5, which may influence
glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy
Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA
homozygotes present in the population and AG heterozygotes had significantly
worse fertility than GG homozygotes. Small changes in milk production associated
with some SNP could not account for the reduced fertility and only SELPEx6 showed
any association with somatic cell count. These results suggest that polymorphisms
in SELP and SELE are associated with the likelihood of successful pregnancy,
potentially through compromised implantation and placental development.
PMID- 28419110
TI - Cocoa pulp in beer production: Applicability and fermentative process
performance.
AB - This work evaluated the effect of cocoa pulp as a malt adjunct on the parameters
of fermentation for beer production on a pilot scale. For this purpose, yeast
isolated from the spontaneous fermentation of cachaca (SC52), belonging to the
strain bank of the State University of Feira de Santana-Ba (Brazil), and a
commercial strain of ale yeast (Safale S-04 Belgium) were used. The beer produced
was subjected to acceptance and purchase intention tests for sensorial analysis.
At the beginning of fermentation, 30% cocoa pulp (adjunct) was added to the wort
at 12 degrees P concentration. The production of beer on a pilot scale was
carried out in a bioreactor with a 100-liter capacity, a usable volume of 60
liters, a temperature of 22 degrees C and a fermentation time of 96 hours. The
fermentation parameters evaluated were consumption of fermentable sugars and
production of ethanol, glycerol and esters. The beer produced using the adjunct
and yeast SC52 showed better fermentation performance and better acceptance
according to sensorial analysis.
PMID- 28419111
TI - Time resolved and label free monitoring of extracellular metabolites by surface
enhanced Raman spectroscopy.
AB - Metabolomics is an emerging field of cell biology that aims at the comprehensive
identification of metabolite levels in biological fluids or cells in a specific
functional state. Currently, the major tools for determining metabolite
concentrations are mass spectrometry coupled with chromatographic techniques and
nuclear magnetic resonance, which are expensive, time consuming and destructive
for the samples. Here, we report a time resolved approach to monitor metabolite
dynamics in cell cultures, based on Surface Enhanced Raman Scattering (SERS).
This method is label-free, easy to use and provides the opportunity to
simultaneously study a broad range of molecules, without the need to process the
biological samples. As proof of concept, NIH/3T3 cells were cultured in vitro,
and the extracellular medium was collected at different time points to be
analyzed with our engineered SERS substrates. By identifying individual peaks of
the Raman spectra, we showed the simultaneous detection of several components of
the conditioned medium, such as L-tyrosine, L-tryptophan, glycine, L
phenylalanine, L-histidine and fetal bovine serum proteins, as well as their
intensity changes during time. Furthermore, analyzing the whole Raman data set
with the Principal Component Analysis (PCA), we demonstrated that the Raman
spectra collected at different days of culture and clustered by similarity,
described a well-defined trajectory in the principal component plot. This
approach was then utilized to determine indirectly the functional state of the
macrophage cell line Raw 264.7, stimulated with the lipopolysaccharide (LPS) for
24 hours. The collected spectra at different time points, clustered by the PCA
analysis, followed a well-defined trajectory, corresponding to the functional
change of cells toward the activated pro-inflammatory state induced by the LPS.
This study suggests that our engineered SERS surfaces can be used as a versatile
tool both for the characterization of cell culture conditions and the functional
state of cells over time.
PMID- 28419113
TI - Evaluation of harvest and information needs for North American sea ducks.
AB - Wildlife managers routinely seek to establish sustainable limits of sport harvest
or other regulated forms of take while confronted with considerable uncertainty.
A growing body of ecological research focuses on methods to describe and account
for uncertainty in management decision-making and to prioritize research and
monitoring investments to reduce the most influential uncertainties. We used
simulation methods incorporating measures of demographic uncertainty to evaluate
risk of overharvest and prioritize information needs for North American sea ducks
(Tribe Mergini). Sea ducks are popular game birds in North America, yet they are
poorly monitored and their population dynamics are poorly understood relative to
other North American waterfowl. There have been few attempts to assess the
sustainability of harvest of North American sea ducks, and no formal harvest
strategy exists in the U.S. or Canada to guide management. The popularity of sea
duck hunting, extended hunting opportunity for some populations (i.e., special
seasons and/or bag limits), and population declines have led to concern about
potential overharvest. We used Monte Carlo simulation to contrast estimates of
allowable harvest and observed harvest and assess risk of overharvest for 7
populations of North American sea ducks: the American subspecies of common eider
(Somateria mollissima dresseri), eastern and western populations of black scoter
(Melanitta americana) and surf scoter (M. perspicillata), and continental
populations of white-winged scoter (M. fusca) and long-tailed duck (Clangula
hyemalis). We combined information from empirical studies and the opinions of
experts through formal elicitation to create probability distributions reflecting
uncertainty in the individual demographic parameters used in this assessment.
Estimates of maximum growth (rmax), and therefore of allowable harvest, were
highly uncertain for all populations. Long-tailed duck and American common eider
appeared to be at high risk of overharvest (i.e., observed harvest < allowable
harvest in 5-7% and 19-26% of simulations, respectively depending on the
functional form of density dependence), whereas the other populations appeared to
be at moderate risk to low risk (observed harvest < allowable harvest in 22-68%
of simulations, again conditional on the form of density dependence). We also
evaluated the sensitivity of the difference between allowable and observed
harvest estimates to uncertainty in individual demographic parameters to
prioritize information needs. We found that uncertainty in overall fecundity had
more influence on comparisons of allowable and observed harvest than adult
survival or observed harvest for all species except long-tailed duck. Although
adult survival was characterized by less uncertainty than individual components
of fecundity, it was identified as a high priority information need given the
sensitivity of growth rate and allowable harvest to this parameter. Uncertainty
about population size was influential in the comparison of observed and allowable
harvest for 5 of the 6 populations where it factored into the assessment. While
this assessment highlights a high degree of uncertainty in allowable harvest, it
provides a framework for integration of improved data from future research and
monitoring. It could also serve as the basis for harvest strategy development as
management objectives and regulatory alternatives are specified by the management
community.
PMID- 28419112
TI - Lens metabolomic profiling as a tool to understand cataractogenesis in Atlantic
salmon and rainbow trout reared at optimum and high temperature.
AB - Periods of high or fluctuating seawater temperatures result in several
physiological challenges for farmed salmonids, including an increased prevalence
and severity of cataracts. The aim of the present study was to compare
cataractogenesis in Atlantic salmon (Salmo salar L.) and rainbow trout
(Oncorhynchus mykiss) reared at two temperatures, and investigate whether
temperature influences lens metabolism and cataract development. Atlantic salmon
(101+/-2 g) and rainbow trout (125+/-3 g) were reared in seawater at either 13
degrees C (optimum for growth) or 19 degrees C during the 35 days experiment (n =
4 tanks for each treatment). At the end of the experiment, the prevalence of
cataracts was nearly 100% for Atlantic salmon compared to ~50% for rainbow trout,
irrespective of temperature. The severity of the cataracts, as evaluated by slit
lamp inspection of the lens, was almost three fold higher in Atlantic salmon
compared to rainbow trout. The global metabolic profile revealed differences in
lens composition and metabolism between the two species, which may explain the
observed differences in cataract susceptibility between the species. The largest
differences were seen in the metabolism of amino acids, especially the histidine
metabolism, and this was confirmed by a separate quantitative analysis. The
global metabolic profile showed temperature dependent differences in the lens
carbohydrate metabolism, osmoregulation and redox homeostasis. The results from
the present study give new insight in cataractogenesis in Atlantic salmon and
rainbow trout reared at high temperature, in addition to identifying metabolic
markers for cataract development.
PMID- 28419114
TI - H-FABP: A new biomarker to differentiate between CT-positive and CT-negative
patients with mild traumatic brain injury.
AB - The majority of patients with mild traumatic brain injury (mTBI) will have normal
Glasgow coma scale (GCS) of 15. Furthermore, only 5%-8% of them will be CT
positive for an mTBI. Having a useful biomarker would help clinicians evaluate a
patient's risk of developing intracranial lesions. The S100B protein is currently
the most studied and promising biomarker for this purpose. Heart fatty-acid
binding protein (H-FABP) has been highlighted in brain injury models and
investigated as a biomarker for stroke and severe TBI, for example. Here, we
evaluate the performances of S100B and H-FABP for differentiating between CT
positive and CT-negative patients. A total of 261 patients with a GCS score of 15
and at least one clinical symptom of mTBI were recruited at three different
European sites. Blood samples from 172 of them were collected <= 6 h after
trauma. Patients underwent a CT scan and were dichotomised into CT-positive and
CT-negative groups for statistical analyses. H-FABP and S100B levels were
measured using commercial kits, and their capacities to detect all CT-positive
scans were evaluated, with sensitivity set to 100%. For patients recruited <= 6 h
after trauma, the CT-positive group demonstrated significantly higher levels of
both H-FABP (p = 0.004) and S100B (p = 0.003) than the CT-negative group. At 100%
sensitivity, specificity reached 6% (95% CI 2.8-10.7) for S100B and 29% (95% CI
21.4-37.1) for H-FABP. Similar results were obtained when including all the
patients recruited, i.e. hospital arrival within 24 h of trauma onset. H-FABP out
performed S100B and thus seems to be an interesting protein for detecting all CT
positive mTBI patients with a GCS score of 15 and at least one clinical symptom.
PMID- 28419115
TI - Properties of the cuticular proteins of Anopheles gambiae as revealed by serial
extraction of adults.
AB - How cuticular proteins (CPs) interact with chitin and with each other in the
cuticle remains unresolved. We employed LC-MS/MS to identify CPs from 5-6 day-old
adults of Anopheles gambiae released after serial extraction with PBS, EDTA, 2-8M
urea, and SDS as well as those that remained unextracted. Results were compared
to published data on time of transcript abundance, localization of proteins
within structures and within the cuticle, as well as properties of individual
proteins, length, pI, percent histidine, tyrosine, glutamine, and number of
AAP[A/V/L] repeats. Thirteen proteins were solubilized completely, all were CPRs,
most belonging to the RR-1 group. Eleven CPs were identified in both soluble
fractions and the final pellet, including 5 from other CP families. Forty-three
were only detected from the final pellet. These included CPRs and members of the
CPAP1, CPF, CPFL, CPLCA, CPLCG, CPLCP, and TWDL families, as well as several low
complexity CPs, not assigned to families and named CPLX. For a given protein,
many histidines or tyrosines or glutamines appear to be potential participants in
cross-linking since we could not identify any peptide bearing these residues that
was consistently absent. We failed to recover peptides from the amino-terminus of
any CP. Whether this implicates that location in sclerotization or some
modification that prevents detection is not known. Soluble CPRs had lower
isoelectric points than those that remained in the final pellet; most members of
other CP families had isoelectric points of 8 or higher. Obviously, techniques
beyond analysis of differential solubility will be needed to learn how CPs
interact with each other and with chitin.
PMID- 28419116
TI - Weak experiences sufficient for creating illusory figures that influence
perception of actual lines.
AB - The question of whether conscious experience is best viewed as graded or
dichotomous has received much scientific attention in recent years as the answer
is relevant not only to models of consciousness, but also to the examination of
neural markers of consciousness in patients and infants. Although some studies
have found evidence of graded perception, it is unclear whether such perception
is simply composed of individual stimulus features perceived in an all-or-none
manner. Here, we examined whether the Kanizsa triangle (an illusory figure that
is supposedly only perceived when all its parts are visible) has an impact on
line length discrimination across four degrees of subjective visibility. We found
that the presence of the Kanizsa triangle biases line length judgments (a
phenomenon called the Ponzo illusion) when participants reported any experience
(even a weak glimpse) of the stimulus. The results support the view that
consciousness is a graded phenomenon. The strength of this support depends on the
assumption that all parts of the illusory figure must be perceived for the
illusion to work but this assumption is not resolved in the present literature.
Currently, evidence can be found both for and against this notion.
PMID- 28419117
TI - Indirect effect of temperature on fish population abundances through phenological
changes.
AB - In response to climate change, earlier phenological events have been reported for
a large range of taxa such that phenological shifts are considered as one of the
fingerprints of the effect of climate change on organisms. Evidence further
suggests that changes in the timing of phenological events might decouple biotic
interactions due to differential phenological adjustment among interacting
species, ultimately leading to population declines. Nonetheless, few studies have
investigated how climate-driven changes in the timing of phenological events
influence population abundances. In this study, we investigated how two
environmental variables known to influence the migration timing of freshwater
fish (i.e. water discharge and temperature) directly or indirectly influenced
abundances of 21 fish species using daily time series gathered at four sites
located in France over a period spanning from 9 to 21 years. We found no evidence
for long-term trends in migration timing or fish abundances over time. Using
piecewise structural equation models, we demonstrate that inter-annual variations
in abundances were driven by inter-annual variations in temperature through
variations in migration timing. Overall, our results suggest that climate change
may concomitantly influence different biological aspects (e.g. phenology,
abundance) of fish species. We argue that considering different responses to
climate change is paramount if we are to improve our understanding of how
organisms and populations are influenced by climate change in order to set-up
efficient conservation strategies.
PMID- 28419118
TI - Fatty liver disease determines the progression of coronary artery calcification
in a metabolically healthy obese population.
AB - OBJECTIVES: Metabolically healthy obese (MHO) phenotype describes an obese state
with a favorable metabolic profile. However, the prognosis of this subpopulation
remains controversial. We aimed to examine whether MHO phenotype is associated
with progression of atherosclerotic activity, reflected as the changes in
coronary artery calcification (CAC) over time. If so, we sought to determine the
role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this
progression. METHODS: We enrolled 1,240 asymptomatic subjects who underwent
repeated CAC score measurement during routine health examinations. CAC score
progression was defined as either incident CAC in a population free of CAC at
baseline, or an increase by >=2.5 units between the baseline and final square
root of CAC scores in participants with detectable CAC at baseline. Subjects were
stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state
using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography.
RESULTS: Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score
progression. The MHO phenotype was not significantly associated with CAC score
progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval
[CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO)
phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was
significantly associated with CAC score progression (multivariate adjusted-OR,
2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the
MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24).
CONCLUSIONS: Obese individuals with FLD have an increased risk of atherosclerosis
progression, despite their healthy metabolic profile. Preventive interventions
targeting cardiometabolic risk factors should be considered in such individuals,
regardless of the weight status.
PMID- 28419119
TI - Plasma ghrelin level and plasma ghrelin/obestatin ratio are related to intestinal
metaplasia in elderly patients with functional dyspepsia.
AB - BACKGROUND: Whether plasma ghrelin/obestatin levels are associated with
Helicobacter pylori (H. pylori) infection, subtypes of functional dyspepsia (FD),
and gastric mucosal histology has not yet been established in elderly patients.
OBJECTIVE: The aim of this study was to determine whether plasma ghrelin and
obestatin levels are related to gastric mucosal histology, H. pylori infection,
and FD subtypes in elderly patients with FD. METHODS: Ninety-two patients
diagnosed with FD and older than 60 years (median age 69.4; range 60-88) were
included. Clinical symptoms investigated included postprandial fullness,
epigastric pain, epigastric soreness, nausea, and vomiting. According to the Rome
III criteria, patients diagnosed with FD were divided into two subtypes:
epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Plasma
ghrelin and obestatin levels were measured using enzyme immunoassay, and
histological examination of gastric mucosa was performed. H. pylori infection was
determined by histopathological examination of gastric mucosal biopsy and/or
Campylobacter-like organism test. RESULTS: In our study, plasma ghrelin levels
and plasma ghrelin/obestatin (G/O) ratio were significantly lower in subjects
with intestinal metaplasia compared with those without intestinal metaplasia
(ghrelin, p = 0.010; G/O ratio, p = 0.012). On the other hand, there were no
significant differences in plasma ghrelin and obestatin levels between H. pylori
positive and H. pylori-negative groups. (ghrelin, p = 0.130; obestatin, p =
0.888). Similarly, no significant differences were detected between the EPS and
PDS groups (ghrelin, p = 0.238; obestatin, p = 0.710). CONCLUSIONS: Patients with
intestinal metaplasia, a known precursor of gastric cancer, had significantly
less plasma ghrelin levels and G/O ratio than those without intestinal
metaplasia.
PMID- 28419120
TI - Structural and functional changes in the microcirculation of lepromatous leprosy
patients - Observation using orthogonal polarization spectral imaging and laser
Doppler flowmetry iontophoresis.
AB - Leprosy is a chronic granulomatous infection of skin and peripheral nerves caused
by Mycobacterium leprae and is considered the main infectious cause of disability
worldwide. Despite the several studies regarding leprosy, little is known about
its effects on microvascular structure and function in vivo. Thus, we have aimed
to compare skin capillary structure and functional density, cutaneous vasomotion
(spontaneous oscillations of arteriolar diameter), which ensures optimal blood
flow distribution to skin capillaries) and cutaneous microvascular blood flow and
reactivity between ten men with lepromatous leprosy (without any other
comorbidity) and ten age- and gender-matched healthy controls. Orthogonal
polarization spectral imaging was used to evaluate skin capillary morphology and
functional density and laser Doppler flowmetry to evaluate blood flow, vasomotion
and spectral analysis of flowmotion (oscillations of blood flow generated by
vasomotion) and microvascular reactivity, in response to iontophoresis of
acetylcholine and sodium nitroprusside. The contribution of different frequency
components of flowmotion (endothelial, neurogenic, myogenic, respiratory and
cardiac) was not statistically different between groups. However, endothelial
dependent and -independent vasodilatations elicited by acetylcholine and sodium
nitroprusside iontophoresis, respectively, were significantly reduced in
lepromatous leprosy patients compared to controls, characterizing the existence
of microvascular dysfunction. These patients also presented a significant
increase in the number of capillaries with morphological abnormalities and in the
diameters of the dermal papilla and capillary bulk when compared to controls. Our
results suggest that lepromatous leprosy causes severe microvascular dysfunction
and significant alterations in capillary structure. These structural and
functional changes are probably induced by exposure of the microvascular bed to
chronic inflammation evoked by the Mycobacterium leprae.
PMID- 28419121
TI - The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels:
Human in vivo measurements.
AB - We optically measured effects of orally available ivacaftor (Kalydeco(r)) on
sweat rates of identified glands in 3 R117H subjects, each having a unique set of
additional mutations, and compared them with 5 healthy control subjects tested
contemporaneously. We injected beta-adrenergic agonists intradermally to
stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which
persists in CF subjects. We focused on an R117H-7T/F508del subject who produced
quantifiable C-sweat off ivacaftor and was available for 1 blinded, 3 off
ivacaftor, and 3 on ivacaftor tests, allowing us to estimate in vivo fold
increase in sweat rates produced by ivacaftor's effect on the open probability
(PO) of R117H-CFTR. Measured sweat rates must be corrected for sweat losses. With
estimated sweat losses of 0.023 to 0.08 nl.gland-1.min-1, ivacaftor increased the
average C-sweat rates 3-7 fold, and estimated function as % of WT were 4.1-12%
off ivacaftor and 21.9-32% on ivacaftor (larger values reflect increased loss
estimates). Based on single tests, an R117H-7T/ R117H-7T subject showed 6-9% WT
function off ivacaftor and 28-43% on ivacaftor. Repeat testing of an R117H
5T/F508del subject detected only trace responding to ivacaftor. We conclude that
in vivo, R117H PO is strongly increased by ivacaftor, but channel number, mainly
determined by variable deletion of exon 10, has a marked influence on outcomes.
PMID- 28419122
TI - Lauric acid as feed additive - An approach to reducing Campylobacter spp. in
broiler meat.
AB - The increasing prevalence of Campylobacter spp. within broiler populations is a
major problem for food safety and consumer protection worldwide. In vitro studies
could already demonstrate that Campylobacter spp. are susceptible to lauric acid.
The purpose of this study was to examine in vivo the influence of lauric acid as
a feed additive on slaughter parameters, muscle fatty acid profile, meat quality
traits and the reduction of Campylobacter coli in inoculated meat of Ross 308
(R308) and Hubbard JA 757 (HJA) broilers in three independent trials (n = 3).
Although slaughter parameters did not show any significant differences, the fatty
acid profile of both breeds revealed significantly higher lauric acid
concentrations (P < 0.0001) in the Musculus pectoralis superficialis of treated
broilers. Comparing both tested breeds, R308 test broilers had significantly
higher lauric acid concentrations than HJA test broilers (P < 0.0001), indicating
a higher conversion rate in those animals. The meat quality traits showed no
differences in the R308 breed (P > 0.05), but HJA test broilers had higher values
for drip loss, electrical conductivity, CIE color values L* and b*, and lower pH
values. The inoculation trials of R308 showed that initial bacterial loads of 5.9
log10 cfu/g were reduced during six days of storage (4 degrees C) to
approximately 4.3 log10 cfu/g in the control groups compared to 3.5 log10 cfu/g
in the treatment groups (P = 0.0295), which could be due to antimicrobial effects
of lauric acid within the muscle. This study therefore suggests that lauric acid
as a feed additive has the potential to improve food safety by reducing the
numbers of Campylobacter coli in broiler meat. However, this effect seems to be
dependent on the breed determining the feed intake capacity, the fat deposition
and therefore the ability to incorporate lauric acid in the muscle.
PMID- 28419123
TI - Low-resistive vibratory penetration in granular media.
AB - Non-cohesive materials such as sand, dry snow or cereals are encountered in
various common circumstances, from everyday situations to industry. The process
of digging into these materials remains a challenge to most animals and machines.
Within the animal kingdom, different strategies are employed to overcome this
issue, including excavation methods used by ants, the two-anchor strategy
employed by soft burrowers such as razor-clams, and undulatory motions exhibited
by sandfish lizards. Despite the development of technology to mimic these
techniques in diggers and robots, the limitations of animals and machines may
differ, and mimicry of natural processes is not necessarily the most efficient
technological strategy. This study presents evidence that the resisting force for
the penetration of an intruder into a dry granular media can be reduced by one
order of magnitude with small amplitude (A ? 10 MUm) and low frequency (f = 50 -
200 Hz) mechanical vibrations. This observed result is attributed to the local
fluidization of the granular bed which induces the rupture of force chains. The
drop in resistive force on entering dry granular materials may be relevant in
technological development in order to increase the efficiency of diggers and
robots.
PMID- 28419124
TI - A randomised controlled trial of losartan as an anti-fibrotic agent in non
alcoholic steatohepatitis.
AB - INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease
worldwide. Experimental and small clinical trials have demonstrated that
angiotensin II blockers (ARB) may be anti-fibrotic in the liver. The aim of this
randomised controlled trial was to assess whether treatment with Losartan for 96
weeks slowed, halted or reversed the progression of fibrosis in patients with non
alcoholic steatohepatitis (NASH). METHODS: Double-blind randomised-controlled
trial of Losartan 50 mg once a day versus placebo for 96 weeks in patients with
histological evidence of NASH. The primary outcome for the study was change in
histological fibrosis stage from pre-treatment to end-of-treatment. RESULTS: The
study planned to recruit 214 patients. However, recruitment was slower than
expected, and after 45 patients were randomised (median age 55; 56% male; 60%
diabetic; median fibrosis stage 2), enrolment was suspended. Thirty-two patients
(15 losartan and 17 placebo) completed follow up period: one patient (6.7%)
treated with losartan and 4 patients (23.5%) in the placebo group were
"responders" (lower fibrosis stage at follow up compared with baseline). The
major reason for slow recruitment was that 39% of potentially eligible patients
were already taking an ARB or angiotensin converting enzyme inhibitor (ACEI), and
15% were taking other prohibited medications. CONCLUSIONS: Due to the widespread
use of ACEI and ARB in patients with NASH this trial failed to recruit sufficient
patients to determine whether losartan has anti-fibrotic effects in the liver.
TRIAL REGISTRATION: ISRCTN 57849521.
PMID- 28419125
TI - Mammographic compression in Asian women.
AB - OBJECTIVES: To investigate: (1) the variability of mammographic compression
parameters amongst Asian women; and (2) the effects of reducing compression force
on image quality and mean glandular dose (MGD) in Asian women based on phantom
study. METHODS: We retrospectively collected 15818 raw digital mammograms from
3772 Asian women aged 35-80 years who underwent screening or diagnostic
mammography between Jan 2012 and Dec 2014 at our center. The mammograms were
processed using a volumetric breast density (VBD) measurement software (Volpara)
to assess compression force, compression pressure, compressed breast thickness
(CBT), breast volume, VBD and MGD against breast contact area. The effects of
reducing compression force on image quality and MGD were also evaluated based on
measurement obtained from 105 Asian women, as well as using the RMI156
Mammographic Accreditation Phantom and polymethyl methacrylate (PMMA) slabs.
RESULTS: Compression force, compression pressure, CBT, breast volume, VBD and MGD
correlated significantly with breast contact area (p<0.0001). Compression
parameters including compression force, compression pressure, CBT and breast
contact area were widely variable between [relative standard deviation
(RSD)>=21.0%] and within (p<0.0001) Asian women. The median compression force
should be about 8.1 daN compared to the current 12.0 daN. Decreasing compression
force from 12.0 daN to 9.0 daN increased CBT by 3.3+/-1.4 mm, MGD by 6.2-11.0%,
and caused no significant effects on image quality (p>0.05). CONCLUSIONS: Force
standardized protocol led to widely variable compression parameters in Asian
women. Based on phantom study, it is feasible to reduce compression force up to
32.5% with minimal effects on image quality and MGD.
PMID- 28419126
TI - Availability and affordability of antimalarial and antibiotic medicines in
Malawi.
AB - BACKGROUND: Availability and affordability of medicines are key determinants of
universal health coverage, yet achieving them presents a major challenge
especially in low-income countries. We here present an analysis of availability
and prices of antimalarial and antibiotic medicines in public, faith-based and
private health facilities in Malawi. Medicines are provided free of charge in the
public health care system of Malawi. In contrast, facilities of the Christian
Health Association of Malawi (CHAM) usually charge their patients for medicines,
as do private for-profit facilities. METHODS: As part of a study on medicine
quality, samples of six antimalarial and six antibiotic medicines were collected
in 31 health facilities in four districts of southern Malawi. These included 15
public facilities (i.e. health centres, district hospitals and central
hospitals), eight CHAM and eight private facilities. Random selection was used in
choosing the included health facilities. The availability of medicines was
recorded, including the number of units which could be collected of each
medicine, as well as the prices of medicines which were charged in CHAM and
private facilities. These data were analyzed using the standard methodology
developed by the World Health Organization (WHO) and Health Action International
(HAI). RESULTS: Availability of the antimalarials artemether/lumefantrine and
sulfadoxine/pyrimethamine, which are provided with financial support from
international donors, was high in public and CHAM facilities (93% and 100%,
respectively). However, availability of antibiotics was much lower (e.g. 40%
availability of amoxicillin tablets/capsules in public health centres). Medicine
prices were lower than reported from many other countries. The median price ratio
(MPR) to a wholesale international procurement price was 2.8 in CHAM facilities
and even lower in the private sector (MPR 2.3). Nevertheless, for 10 of the 12
investigated medicines the cost for one course of treatment exceeded the daily
wage of a low-paid government worker in Malawi and therefore had to be considered
as unaffordable for a major part of the population. CONCLUSIONS: Continued
efforts are required to improve the availability of essential medicines in
Malawi. The free provision of medicines in the public health care system remains
important in order to achieve universal health coverage, due to the low income in
this country.
PMID- 28419127
TI - Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous
oxide emissions from vegetable field in south China.
AB - Globally, vegetable fields are the primary source of greenhouse gas emissions. A
closed-chamber method together with gas chromatography was used to measure the
fluxes of nitrous oxide (N2O) emissions in typical vegetable fields planted with
four vegetables sequentially over time in the same field: endive, lettuce,
cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with
the N2O emission peak varying greatly among the crops. In addition, N2O emissions
were linearly associated with the nitrogen (N) application rate (r = 0.8878, n =
16). Excessive fertilizer N application resulted in N loss through nitrous oxide
gas emitted from the vegetable fields. Compared with a conventional fertilization
(N2) treatment, the cumulative N2O emissions decreased significantly in the
growing seasons of four plant species from an nitrogen synergist (a nitrification
inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively.
However, the effects of biochar on reducing N2O emissions became more obvious
than that of dicyandiamide over time. The yield-scaled N2O emissions in
consecutive growing seasons for four species increased with an increase in the N
fertilizer application rate, and with continuous application of N fertilizer.
This was especially true for the high N fertilizer treatment that resulted in a
risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and
biochar significantly decreased yield-scaled N2O-N emissions by an average of
45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive
four vegetable seasons. The results demonstrated that the addition of
dicyandiamide or biochar in combination with application of a rational amount of
N could provide the best strategy for the reduction of greenhouse gas emissions
in vegetable field in south China.
PMID- 28419128
TI - Cytoskeletal stability and metabolic alterations in primary human macrophages in
long-term microgravity.
AB - The immune system is one of the most affected systems of the human body during
space flight. The cells of the immune system are exceptionally sensitive to
microgravity. Thus, serious concerns arise, whether space flight associated
weakening of the immune system ultimately precludes the expansion of human
presence beyond the Earth's orbit. For human space flight, it is an urgent need
to understand the cellular and molecular mechanisms by which altered gravity
influences and changes the functions of immune cells. The CELLBOX-PRIME (=
CellBox-Primary Human Macrophages in Microgravity Environment) experiment
investigated for the first time microgravity-associated long-term alterations in
primary human macrophages, one of the most important effector cells of the immune
system. The experiment was conducted in the U.S. National Laboratory on board of
the International Space Station ISS using the NanoRacks laboratory and Biorack
type I standard CELLBOX EUE type IV containers. Upload and download were
performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 /
May 18th, 2014. Surprisingly, primary human macrophages exhibited neither
quantitative nor structural changes of the actin and vimentin cytoskeleton after
11 days in microgravity when compared to 1g controls. Neither CD18 or CD14
surface expression were altered in microgravity, however ICAM-1 expression was
reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF
MS, revealed eight metabolites with significantly different quantities when
compared to 1g controls. In particular, the significant increase of free fucose
in the cell culture supernatant was associated with a significant decrease of
cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell
surface-bound fucose may contribute to functional impairments, e.g. the
activation of T cells, migration and activation of the innate immune response. We
assume that the surprisingly small and non-significant cytoskeletal alterations
represent a stable "steady state" after adaptive processes are initiated in the
new microgravity environment. Due to the utmost importance of the human
macrophage system for the elimination of pathogens and the clearance of apoptotic
cells, its apparent robustness to a low gravity environment is crucial for human
health and performance during long-term space missions.
PMID- 28419129
TI - Factors related to axial length elongation and myopia progression in
orthokeratology practice.
AB - PURPOSE: To investigate which baseline factors are predictive for axial length
growth over an average period of 2.5 years in a group of children wearing
orthokeratology (OK) contact lenses. METHODS: In this retrospective study, the
clinical records of 249 new OK wearers between January 2012 and December 2013
from the contact lens clinic at the Eye and ENT Hospital of Fudan University were
reviewed. The primary outcome measure was axial length change from baseline to
the time of review (July-August 2015). Independent variables included baseline
measures of age at initiation of OK wear, gender, refractive error (spherical
equivalent), astigmatism, average keratometry, corneal toricity, central corneal
thickness, white-to-white corneal diameter, pupil size, corneal topography
eccentricity value (e-value), intraocular pressure (IOP) and total time in follow
up (months total). The contributions of all independent variables on axial length
change at the time of review were assessed using univariate and multivariable
regression analyses. RESULTS: Univariate analyses of the right eyes of 249 OK
patients showed that smaller increases in axial length were associated with older
age at the onset of OK lens wear, greater baseline spherical equivalent myopic
refractive error, less time in follow-up and a smaller e-value. Multivariable
analyses of the significant right eye variables showed that the factors
associated with smaller axial length growth were older age at the onset of OK
lens wear (p<0.0001), greater baseline spherical equivalent myopic refractive
error (p = 0.0046) and less time in follow-up (p<0.0001). CONCLUSIONS: The
baseline factors demonstrating the greatest correlation with reduced axial length
elongation during OK lens wear in myopic children included greater baseline
spherical equivalent myopic refractive error and older age at the onset of OK
lens wear.
PMID- 28419130
TI - Virus-induced down-regulation of GmERA1A and GmERA1B genes enhances the stomatal
response to abscisic acid and drought resistance in soybean.
AB - Drought is a major threat to global soybean production. The limited
transformation potential and polyploid nature of soybean have hindered functional
analysis of soybean genes. Previous research has implicated farnesylation in the
plant's response to abscisic acid (ABA) and drought tolerance. We therefore used
virus-induced gene silencing (VIGS) to evaluate farnesyltransferase genes,
GmERA1A and GmERA1B (Glycine max Enhanced Response to ABA1-A and -B), as
potential targets for increasing drought resistance in soybean. Apple latent
spherical virus (ALSV)-mediated GmERA1-down-regulated soybean leaves displayed an
enhanced stomatal response to ABA and reduced water loss and wilting under
dehydration conditions, suggesting that GmERA1A and GmERA1B negatively regulate
ABA signaling in soybean guard cells. The findings provide evidence that the ALSV
VIGS system, which bypasses the need to generate transgenic plants, is a useful
tool for analyzing gene function using only a single down-regulated leaf. Thus,
the ALSV-VIGS system could constitute part of a next-generation molecular
breeding pipeline to accelerate drought resistance breeding in soybean.
PMID- 28419131
TI - Aflatoxin levels in sunflower seeds and cakes collected from micro- and small
scale sunflower oil processors in Tanzania.
AB - Aflatoxin, a mycotoxin found commonly in maize and peanuts worldwide, is
associated with liver cancer, acute toxicosis, and growth impairment in humans
and animals. In Tanzania, sunflower seeds are a source of snacks, cooking oil,
and animal feed. These seeds are a potential source of aflatoxin contamination.
However, reports on aflatoxin contamination in sunflower seeds and cakes are
scarce. The objective of the current study was to determine total aflatoxin
concentrations in sunflower seeds and cakes from small-scale oil processors
across Tanzania. Samples of sunflower seeds (n = 90) and cakes (n = 92) were
collected across two years, and analyzed for total aflatoxin concentrations using
a direct competitive enzyme-linked immunosorbent assay (ELISA). For seed samples
collected June-August 2014, the highest aflatoxin concentrations were from Dodoma
(1.7-280.6 ng/g), Singida (1.4-261.8 ng/g), and Babati-Manyara (1.8-162.0 ng/g).
The highest concentrations for cakes were from Mbeya (2.8-97.7 ng/g), Dodoma (1.9
88.2 ng/g), and Singida (2.0-34.3 ng/g). For seed samples collected August
October 2015, the highest concentrations were from Morogoro (2.8-662.7 ng/g),
Singida (1.6-217.6 ng/g) and Mbeya (1.4-174.2 ng/g). The highest concentrations
for cakes were from Morogoro (2.7-536.0 ng/g), Dodoma (1.4-598.4 ng/g) and
Singida (3.2-52.8 ng/g). In summary, humans and animals are potentially at high
risk of exposure to aflatoxins through sunflower seeds and cakes from micro-scale
millers in Tanzania; and location influences risk.
PMID- 28419132
TI - Spectrophotometric and molecular modelling studies on in vitro interaction of
tyrosine kinase inhibitor linifanib with bovine serum albumin.
AB - Linifanib (LNF) possess antitumor activity and acts by inhibiting receptor
tyrosine kinase VEGF and PDGF. The interaction of BSA with the drug can provide
valuable information regarding the pharmacokinetic and pharmacodynamics behavior
of drug. In our study the spectrophotometric methods and molecular docking
studies were executed to understand the interaction behavior of BSA and LNF. BSA
has an intrinsic fluorescence and that fluorescence was quenched by LNF. This
quenching process was studied at three different temperatures of 288, 300and 308
K. The interaction between LNF and BSA was due to static quenching because the
Ksv (Stern-Volmer constant) at 288 K was higher than at 300 and 308 K. Kq
(quenching rate constant) behaved in a similar fashion as the Ksv. Several other
parameters like binding constants, number of binding sites and binding energy in
addition to molecular docking studies were also used to evaluate the interaction
process. A decrease in the binding constants was observed with increasing
temperatures and the binding site number approximated unity. The decreasing
binding constant indicates LNF-BSA complex stability. The site mark competition
experiment confirmed the binding site for LNF was located on site II of BSA. UV
visible studies along with synchronous fluorescence confirm a small change in the
conformation of BSA upon interaction with LNF. The thermodynamic analysis
provided the values for free energy DeltaG0, DeltaH0 and DeltaS0. The DeltaG0 at
the 288, 300 and 308 K ranged in between -21.5 to -23.3 kJ mol-1, whereas the
calculated values of DeltaH (-55.91 kJ mol-1) and DeltaS0 (-111.74 J mol-1.K-1).
The experimental and molecular docking results suggest that the interaction
between LNF and BSA was spontaneous and they exhibited hydrogen bonding and van
der Waals force between them.
PMID- 28419133
TI - Reproductive toxicity after levetiracetam administration in male rats: Evidence
for role of hormonal status and oxidative stress.
AB - Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of
epilepsy because of its excellent safety profile in all age groups. It is
remarkable that there are no studies evaluating the toxic effects of this drug on
the male reproductive system, as it is commonly used in male patients of
reproductive age. From this point of view, our aim was to evaluate the possible
toxic effects of LEV on the male reproductive system. Therefore, LEV was
administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive
days. At the end of this period, alterations to body and organ weights were
calculated, and sperm concentration, motility, and morphology were investigated
by a computer-assisted sperm analysis system. Sperm DNA damage was determined by
comet assay and histopathological examination of the testes was carried out.
Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone
(LH) levels were measured by ELISAs to determine the effects of hormonal status,
while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in
the testes were measured by colorimetric assay kits to determine the role of
oxidative status in potential toxicity. According to the results, sperm quality
was decreased by LEV treatment in a dose-dependent manner. LEV induced
significant DNA damage in the 150 and 300 mg/kg LEV-administered groups.
Histopathology of the testes showed that LEV resulted in testicular injury in the
300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were
significantly decreased in the 300 mg/kg LEV-administered group. Glutathione,
superoxide dismutase, and catalase levels were significantly decreased in all
experimental groups while malondialdehyde levels were significantly increased in
150 and 300 mg/kg LEV-administered groups. According to these results, it was
determined that LEV administration decreased sperm quality and it was alleged
that hormonal alteration and oxidative stress are potential contributors to
reproductive toxicity.
PMID- 28419134
TI - Development of mismatch amplification mutation assays for the differentiation of
MS1 vaccine strain from wild-type Mycoplasma synoviae and MS-H vaccine strains.
AB - Mycoplasma synoviae is an economically significant pathogen in the poultry
industry, inducing respiratory disease and infectious synovitis in chickens and
turkeys, and eggshell apex abnormality in chickens. Eradication, medication and
vaccination are the options for controlling M. synoviae infection. Currently
there are two commercial, live, attenuated vaccines available against M.
synoviae: the temperature sensitive MS-H vaccine strain and the NAD independent
MS1 vaccine strain. Differentiation of vaccine strains from field isolates is
essential during vaccination and eradication programs. The present study provides
melt-curve and agarose gel based mismatch amplification mutation assays (MAMA) to
discriminate the MS1 vaccine strain from the MS-H vaccine strain and wild-type M.
synoviae isolates. The assays are based on the A/C single nucleotide polymorphism
at nt11 of a HIT family protein coding gene. The melt- and agarose-MAMAs reliably
distinguish the MS1 vaccine strain genotype from the MS-H vaccine strain and wild
type M. synoviae isolate genotype from 102 template number/DNA sample. No cross
reactions with other avian Mycoplasma species were observed. The assays can be
performed directly on clinical samples and they can be run simultaneously with
the previously described MAMAs designed for the discrimination of the MS-H
vaccine strain. The developed assays are applicable in laboratories with limited
facilities and promote the rapid, simple and cost effective differentiation of
the MS1 vaccine strain.
PMID- 28419135
TI - An organotypic slice culture to study the formation of calyx of Held synapses in
vitro.
AB - The calyx of Held, a large axo-somatic relay synapse containing hundreds of
presynaptic active zones, is possibly the largest nerve terminal in the mammalian
CNS. Studying its initial growth in-vitro might provide insights into the
specification of synaptic connection size in the developing brain. However,
attempts to maintain calyces of Held in organotypic cultures have not been
fruitful in past studies. Here, we describe an organotypic slice culture method
in which calyces of Held form in-vitro. We made coronal brainstem slices with an
optimized slice angle using newborn mice in which calyces have not yet formed;
the presynaptic bushy cells were genetically labeled using the Math5 promoter.
After six to nine days of culturing, we readily observed large Math5-positive
nerve terminals in the medial nucleus of the trapezoid body (MNTB), but not in
the neighboring lateral superior olive nucleus (LSO). These calyx-like synapses
expressed the Ca2+- sensor Synaptotagmin-2 (Syt-2) and the Ca2+ binding protein
Parvalbumin (PV), two markers of developing calyces of Held in vivo. Application
of the BMP inhibitor LDN-193189 significantly inhibited the growth of calyx
synapses, demonstrating the feasibility of long-term pharmacological manipulation
using this organotypic culture method. These experiments provide a method for
organotypic culturing of calyces of Held, and show that the formation of calyx
like synapses onto MNTB neurons can be preserved in-vitro. Furthermore, our study
adds pharmacological evidence for a role of BMP-signaling in the formation of
large calyx of Held synapses.
PMID- 28419136
TI - Occurrence of Leishmania infantum in the central nervous system of naturally
infected dogs: Parasite load, viability, co-infections and histological
alterations.
AB - Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum
and little is known about the occurrence and pathogenesis of this parasite in the
CNS. The aims of this study were to evaluate the occurrence, viability and load
of L. infantum in the CNS, and to identify the neurological histological
alterations associated with this protozoan and its co-infections in naturally
infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum
was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were
analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the
rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and
spleen samples were submitted to parasitological culture, qPCR, and histological
techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis
antibodies in serum and distemper virus antigens in CSF were investigated. None
of the dogs showed neurological signs. All dogs tested positive for L. infantum
in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal
cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61%
of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31%
of the animals; of these, 66% were seropositive for E. canis and/or T. gondii.
Amastigote forms were associated with granulomatous non-suppurative
encephalomyelitis in a dog without evidence of co-infections. The highest
frequency of L. infantum DNA was observed in the brain (98%), followed by the
spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in
CNS was found in the spinal cord. These results demonstrate that L. infantum can
cross the blood-brain barrier, spread through CSF, and cause active infection in
the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the
CNS that can lead to neurological signs with progression of the disease.
PMID- 28419137
TI - Transcriptional changes in litchi (Litchi chinensis Sonn.) inflorescences treated
with uniconazole.
AB - In Arabidopsis, treating shoots with uniconazole can result in enhanced primary
root elongation and bolting delay. Uniconazole spraying has become an important
cultivation technique in controlling the flowering and improving the fruit
setting of litchi. However, the mechanism by which uniconazole regulates the
complicated developmental processes in litchi remains unclear. This study aimed
to determine which signal pathways and genes drive the responses of litchi
inflorescences to uniconazole treatment. We monitored the transcriptional
activity in inflorescences after uniconazole treatment by Illumina sequencing
technology. The global expression profiles of uniconazole-treated litchi
inflorescences were compared with those of the control, and 4051 differentially
expressed genes were isolated. KEGG pathway enrichment analysis indicated that
the plant hormone signal transduction pathway served key functions in the flower
developmental stage under uniconazole treatment. Basing on the transcriptional
analysis of genes involved in flower development, we hypothesized that
uniconazole treatment increases the ratio of female flowers by activating the
transcription of pistil-related genes. This phenomenon increases opportunities
for pollination and fertilization, thereby enhancing the fruit-bearing rate. In
addition, uniconazole treatment regulates the expression of unigenes involved in
numerous transcription factor families, especially the bHLH and WRKY families.
These findings suggest that the uniconazole-induced morphological changes in
litchi inflorescences are related to the control of hormone signaling, the
regulation of flowering genes, and the expression levels of various transcription
factors. This study provides comprehensive inflorescence transcriptome data to
elucidate the molecular mechanisms underlying the response of litchi flowers to
uniconazole treatment and enumerates possible candidate genes that can be used to
guide future research in controlling litchi flowering.
PMID- 28419138
TI - Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with
scrub typhus.
AB - BACKGROUND: The aim of this study is to investigate the clinical significance of
neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1
(KIM-1) for acute kidney injury (AKI) in patients with scrub typhus. METHODS:
From 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we
enrolled 138 patients who were followed up until renal recovery or for at least 3
months. We measured serum and urine NGAL and KIM-1 levels and evaluated
prognostic factors affecting scrub typhus-associated AKI. RESULTS: Of the 138
patients, 25 had scrub typhus-associated AKI. The incidence of AKI was 18.1%; of
which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure,
respectively, according to RIFLE criteria. Compared with patients in the non-AKI
group, patients in the AKI group were older and showed higher total leukocyte
counts and hypoalbuminemia or one or more comorbidities such as hypertension (72%
vs 33%, p<0.01), diabetes (40% vs 14%, p<0.01), or chronic kidney disease (32% vs
1%, p<0.01). In addition, serum NGAL values (404+/- 269 vs 116+/- 78 ng/mL,
P<0.001), KIM-1 values (0.80+/- 0.52 vs 0.33+/- 0.68 ng/mL, P<0.001), urine
NGAL/creatinine values (371+/- 672 vs 27+/- 39 ng/mg, P<0.001) and urine KIM
1/creatinine values (4.04+/- 2.43 vs 2.38+/- 1.89 ng/mg, P<0.001) were higher in
the AKI group than in the non-AKI group. By multivariate logistic regression,
serum NGAL and the presence of chronic kidney disease were significant predictors
of AKI. CONCLUSION: Serum NGAL might be an additive predictor for scrub typhus
associated AKI.
PMID- 28419139
TI - Skeletal-related events and mortality among men diagnosed with advanced prostate
cancer: The impact of alternative measures of radiation to the bone.
AB - PURPOSE/OBJECTIVE(S): Skeletal-related events (SREs), which include radiation to
the bone (RtB), can occur among patients with bone metastasis (BM). There is a
recognized potential for misclassification of RtB when using claims data. We
compared alternative measures of RtB to better understand their impact on SRE
prevalence and SRE-related mortality. METHODS AND MATERIALS: We analyzed data for
stage IV prostate cancer (PCa) cases identified between 2005 and 2009 in the
Surveillance, Epidemiology, and End Results registry linked with Medicare claims.
We created two measures of RtB: 1) a literature-based measure requiring the
presence of a prior claim with a BM code; 2) a new measure requiring either that
the BM code coincided with the radiation episode or that the duration of the
radiation episode was less than or equal to 4 weeks. We estimated adjusted hazard
ratios of an SRE using both measures among stratified samples: no metastasis
(M0), metastasis to bone (M1b) and other sites (M1c). RESULTS: The study sample
included 5,074 men with stage IV PCa (median age 77 years), of whom 22% had M0,
54% had M1b, and 24% had M1c disease at time of PCa diagnosis. Based on
Approaches 1 and 2, the proportion with probable RtB was 5% and 8% among M0, 30%
and 30% among M1b, and 25% and 27% among M1c patients. Among M0 patients, the
adjusted hazard ratio (AHR) associated with an SRE was 1.27 when using Approach 1
(95% confidence interval, CI: 0.95-1.7) and 1.49 when using Approach 2 (95% CI:
1.14-1.96). However, the impact of SREs on mortality did not differ between both
approaches among M1b and M1c patients. CONCLUSION: We found that alternative
measures used to define RtB as SRE in claims data impact conclusions regarding
the effect of SREs on mortality among M0 but not M1 patients.
PMID- 28419141
TI - Ghrelin is a prognostic marker and a potential therapeutic target in breast
cancer.
AB - Ghrelin and obestatin are gastrointestinal peptides, encoded by the same
preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has
been implicated in breast cancer tumorigenesis. Despite recent advances in breast
cancer management the need for new prognostic markers and potential therapeutic
targets in breast cancer remains high. We studied the prognostic impact of
ghrelin and obestatin in women with node negative breast cancer. Within a cohort
of women with breast cancer with tumor size <= 50 mm, no lymph node metastases
and no initiation of adjuvant chemotherapy, 190 women were identified who died
from breast cancer and randomly selected 190 women alive at the corresponding
time as controls. Tumor tissues were immunostained with antibodies versus the
peptides. Ghrelin expression was associated with better breast cancer specific
survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate
models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89).
Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin
expression is independent prognostic factor for breast cancer death in node
negative patients-halving the risk for dying of breast cancer. Our data implies
that ghrelin could be a potential therapeutic target in breast cancer treatment.
PMID- 28419140
TI - Niche matters: The comparison between bone marrow stem cells and endometrial stem
cells and stromal fibroblasts reveal distinct migration and cytokine profiles in
response to inflammatory stimulus.
AB - OBJECTIVE: Intrinsic inflammatory characteristics play a pivotal role in stem
cell recruitment and homing through migration where the subsequent change in
niche has been shown to alter these characteristics. The bone marrow mesenchymal
stem cells (bmMSCs) have been demonstrated to migrate to the endometrium
contributing to the stem cell reservoir and regeneration of endometrial tissue.
Thus, the aim of the present study was to compare the inflammation-driven
migration and cytokine secretion profile of human bmMSCs to endometrial
mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). MATERIALS AND
METHODS: The bmMSCs were isolated from bone marrow aspirates through culturing,
whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their
surface marker, proliferation profiles and migration properties towards serum and
inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets
was analysed in each cell type at basal level along with lipopolysaccharide (LPS)
induced state. RESULTS: Both stem cell types, bmMSCs and eMSCs, presented with
similar stem cell surface marker profiles as well as possessed high proliferation
and migration potential compared to eSFs. In multiplex assays, the secretion of
16 cytokine targets was detected and LPS stimulation expanded the cytokine
secretion pattern by triggering the secretion of several targets. The bmMSCs
exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)
A, stromal cell-derived factor-1 alpha (SDF)-1alpha, interleukin-1 receptor
antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte
chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)1alpha and
RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8
secretion was higher in both endometrial cell types compared to bmMSCs.
CONCLUSION: Our results highlight that similar to bmMSCs, the eMSCs possess high
migration activity while the differentiation process towards stromal fibroblasts
seemed to result in loss of stem cell surface markers, minimal migration activity
and a subtler cytokine profile likely contributing to normal endometrial
function.
PMID- 28419142
TI - Multispot single-molecule FRET: High-throughput analysis of freely diffusing
molecules.
AB - We describe an 8-spot confocal setup for high-throughput smFRET assays and
illustrate its performance with two characteristic experiments. First,
measurements on a series of freely diffusing doubly-labeled dsDNA samples allow
us to demonstrate that data acquired in multiple spots in parallel can be
properly corrected and result in measured sample characteristics consistent with
those obtained with a standard single-spot setup. We then take advantage of the
higher throughput provided by parallel acquisition to address an outstanding
question about the kinetics of the initial steps of bacterial RNA transcription.
Our real-time kinetic analysis of promoter escape by bacterial RNA polymerase
confirms results obtained by a more indirect route, shedding additional light on
the initial steps of transcription. Finally, we discuss the advantages of our
multispot setup, while pointing potential limitations of the current single laser
excitation design, as well as analysis challenges and their solutions.
PMID- 28419143
TI - Chaetocin induces apoptosis in human melanoma cells through the generation of
reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its
anti-tumor activity in vivo.
AB - Chaetocin is a small-molecule natural product produced by Chaetomium species
fungi, and it has a potent anti-proliferative pharmacological activity on various
cancer cells. However, the effect of chaetocin on anti-melanoma pharmacological
role has not been investigated. Therefore, in this study, we explored the effect
of chaetocin on cell proliferation in the human melanoma Sk-Mel-28 and A375 cells
and the growth of tumor xenografts in nude mice. The results indicated that
chaetocin treatment significantly suppressed cell proliferation and induced
apoptosis in the Sk-Mel-28 and A375 cells in a dose- and time-dependent manner.
Furthermore, chaetocin treatment resulted in an increased level of cellular
reactive oxygen species (ROS), and pre-incubation of cells with N-acetylcysteine
(NAC) significantly abrogated chaetocin-induced apoptosis in the melanoma cells.
A significant reduction of mitochondrial membrane potential and the release of
cytochrome c were observed after chaetocin treatment. Additionally, chaetocin
treatment significantly up-regulated the protein levels of Bax, cleaved caspase
9/-3, simultaneously down-regulated the protein levels of Bcl-2, procaspase-9/-3,
and activated caspase-9/-3 activity in the melanoma cells. The in vivo data
demonstrated that chaetocin treatment significantly inhibited the growth of
melanoma tumor xenografts in nude mice, which was closely associated with
apoptosis induction, a reduced level of PCNA (proliferating cell nuclear antigen)
expression, and activation of capase-9/-3 in tumor xenografts. These are the
first data to demonstrate that chaetocin exerts a proapoptotic activity on human
melanoma cells through ROS generation and the intrinsic mitochondrial pathway.
Therefore, chaetocin might represent an effective candidate for melanoma
chemotherapy.
PMID- 28419144
TI - Stepwise inhibition of T cell recruitment at post-capillary venules by orally
active desulfated heparins in inflammatory arthritis.
AB - Identification of the structure-function relationship of heparin, particularly
between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory
activities, is critical in order to evaluate the biological effects of heparin,
especially in conjunction with modifications for oral formulation. In this study,
we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic
modifications have differential effects on the blocking of interactions between
sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was
consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O
desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH
to interfere with T cell adhesion via selectin-sLeX interactions. Furthermore,
6DSHbD coated on the apical surface of inflamed endothelium directly blocked the
adhesive interactions of circulating T cells, which was confirmed in vivo by
suppressing T cell adhesion at post-capillary venular endothelium. Thus, in
series with our previous study demonstrating inhibition of transendothelial
migration, oral delivery of low anticoagulant LMWH to venular endothelium of
inflamed joint tissues ameliorated arthritis by the stepwise inhibition of T cell
recruitment and provides a rationale for the development of modified oral
heparins as innovative agents for the treatment of chronic inflammatory
arthritis.
PMID- 28419145
TI - Apomixis frequency under stress conditions in weeping lovegrass (Eragrostis
curvula).
AB - To overcome environmental stress, plants develop physiological responses that are
triggered by genetic or epigenetic changes, some of which involve DNA
methylation. It has been proposed that apomixis, the formation of asexual seeds
without meiosis, occurs through the temporal or spatial deregulation of the
sexual process mediated by genetic and epigenetic factors influenced by the
environment. Here, we explored whether there was a link between the occurrence of
apomixis and various factors that generate stress, including drought stress, in
vitro culture, and intraspecific hybridization. For this purpose, we monitored
the embryo sacs of different weeping lovegrass (Eragrostis curvula [Schrad.]
Nees) genotypes after the plants were subjected to these stress conditions.
Progeny tests based on molecular markers and genome methylation status were
analyzed following the stress treatment. When grown in the greenhouse, the
cultivar Tanganyika INTA generated less than 2% of its progeny by sexual
reproduction. Plants of this cultivar subjected to different stresses showed an
increase of sexual embryo sacs, demonstrating an increased expression of
sexuality compared to control plants. Plants of the cv. Tanganyika USDA did not
demonstrate the ability to generate sexual embryo sacs under any conditions and
is therefore classified as a fully apomictic cultivar. We found that this change
in the prevalence of sexuality was correlated with genetic and epigenetic changes
analyzed by MSAP and AFLPs profiles. Our results demonstrate that different
stress conditions can alter the expression of sexual reproduction in facultative
tetraploid apomictic cultivars and when the stress stops the reproductive mode
shift back to the apomixis original level. These data together with previous
observations allow us to generate a hypothetical model of the regulation of
apomixis in weeping lovegrass in which the genetic/s region/s that condition
apomixis, is/are affected by ploidy, and is/are subjected to epigenetic control.
PMID- 28419146
TI - Household crowding as a potential mediator of socioeconomic determinants of
tuberculosis incidence in Brazil.
AB - Although many studies have identified social conditions associated with
tuberculosis, contextual and individual factors have rarely been analysed
simultaneously. Consequently, we aimed to identify contextual and individual
factors associated with tuberculosis incidence in general population in Brazil in
2010. We also assessed whether household crowding mediates the association
between socioeconomic determinants and tuberculosis incidence. Individual data of
tuberculosis cases were obtained from 5,565 municipalities in Brazil in 2010
(last year of national census), and merged with contextual variables. The
associations were evaluated in a multilevel analysis using negative binomial
regression. After adjusting for individual factors (age, sex and race) and
geographic region, the following contextual factors were associated with
tuberculosis incidence rate: AIDS incidence rate [incidence rate ratio (IRR),
1.21; 95% confidence interval (CI), 1.18-1.24], unemployment rate (IRR, 1.16; 95%
CI, 1.13-1.19), Gini coefficient (IRR, 1.05; 95% CI, 1.02-1.08), proportion of
inmates (IRR, 1.11; 95% CI, 1.09-1.14), mean per capita household income (IRR,
0.94; 95% CI, 0.91-0.97) and primary care coverage (IRR, 0.94; 95% CI, 0.92
0.96). Inclusion of household crowding in the multivariate model led to a loss of
the associations of both Gini coefficient and mean per capita household income.
In conclusion, our findings suggest that income inequality and poverty, as
determinants of tuberculosis incidence, can be mediated by household crowding.
Moreover, prison population can represent a potential social reservoir of
tuberculosis in Brazil and should be addressed as a priority for disease control.
Finally, the negative association between primary health coverage and
tuberculosis incidence highlights the importance of this level of care as a
strategy to control this disease.
PMID- 28419147
TI - Cone-beam computed tomography with automated bone subtraction in preoperative
embolization for pelvic bone tumors.
AB - PURPOSE: To evaluate the usefulness of cone-beam computed tomography with
automated bone subtraction (CBCT-ABS) in the preoperative embolization of
hypervascular tumors located in the pelvic bone. MATERIALS AND METHODS: This
retrospective study included 26 patients with pelvic bone tumors who underwent
preoperative embolization between January 2014 and October 2016. A CBCT-ABS scan
was taken in a total of 17 patients (CBCT-ABS group), and only a series of
digital subtraction angiographies (DSAs) was taken in the remaining 9 patients
(DSA group). The percent devascularization, number of angiographic runs, total
dose-area product (DAP), fluoroscopy time, interventional procedure time,
operative time, and estimated blood loss were compared between the two groups
using Mann-Whitney test. RESULTS: The percent devascularization, interventional
procedure time, fluoroscopy time, operative time, and estimated blood loss were
not statistically different between the two groups (p > 0.05). On the other hand,
the number of angiographic runs in the CBCT-ABS group was significantly lower
than that in the DSA group (p = 0.029). The total DAP of the CBCT-ABS group
(mean, 17700.7 MUGym2) was higher than that of the DSA group (mean, 8939.4
MUGym2) (p = 0.002). CONCLUSIONS: The use of CBCT-ABS during the preoperative
embolization of pelvic bone tumors significantly reduces the number of
angiographic runs at the cost of an increased radiation dose.
PMID- 28419148
TI - How long to rest in unpredictably changing habitats?
AB - In the present study, we investigated the optimum length of prolonged dormancy
(developmental arrest extending over favourable periods) of organisms under
uncertain environmental conditions. We used an artificial life model to simulate
the evolution of suspended development in the ontogenesis of organisms inhabiting
unpredictably changing habitats. A virtual population of semelparous
parthenogenetic individuals that varied in a duration of developmental arrest
competed for limited resources. At a constant level of available resources,
uninterrupted development was the superior life strategy. Once population
fluctuations appeared (generated by the stochastic variability of available
resources), temporal developmental arrest became more advantageous than
continuous development. We did not observe the selection of the optimum length of
dormancy, but rather the evolution of a diversified period of developmental
arrest. The fittest organisms employed bet-hedging strategy and produced
diversified dormant forms postponing development for a different number of
generations (from 0 to several generations, in decreasing or equal proportions).
The maximum length of suspended development increased asymptotically with
increasing environmental variability and was inversely related to the mortality
of dormant forms. The prolonged dormancy may appear beneficial not only in
erratic habitats but also in seasonal ones that are exposed to long-term
variability of environmental conditions during the growing seasons. In light of
our simulations the phenomenon of very long diapause (VLD), lasting tens to
thousands of generations, which is occasionally observed in ontogenesis of some
living creatures, may not be explained by the benefits of bet-hedging revival
strategies. We propose an alternative reasoning for the expression of VLD.
PMID- 28419149
TI - Mobile health treatment support intervention for HIV and tuberculosis in
Mozambique: Perspectives of patients and healthcare workers.
AB - BACKGROUND: Studies have been conducted in developing countries using SMS to
communicate with patients to reduce the number of missed appointments and improve
retention in treatment, however; very few have been scaled up. One possible
reason for this could be that patients or staff are dissatisfied with the method
in some way. This paper reports a study of patients' and healthcare workers'
(HCW) views on an mHealth intervention aiming to support retention in
antiretroviral therapy (ART) and tuberculosis (TB) treatment in Mozambique.
METHODS: The study was conducted at five healthcare centres in Mozambique.
Automated SMS health promotions and reminders were sent to patients in a RCT. A
total of 141 patients and 40 HCWs were interviewed. Respondents rated usefulness,
perceived benefits, ease of use, satisfaction, and risks of the SMS system using
a Likert scale questionnaire. A semi-structured interview guide was followed.
Interviews were transcribed and thematic analysis was conducted. RESULTS: Both
patients and HCW found the SMS system useful and reliable. Most highly rated
positive effects were reducing the number of failures to collect medication and
avoiding missing appointments. Patients' confidence in the system was high. Most
perceived the system to improve communication between health-care provider and
patient and assist in education and motivation. The automatic recognition of
questions from patients and the provision of appropriate answers (a unique
feature of this system) was especially appreciated. A majority would recommend
the system to other patients or healthcare centres. Risks also were mentioned,
mostly by HCW, of unintentional disclosure of health status in cases where
patients use shared phones. CONCLUSIONS: The results suggest that SMS technology
for HIV and TB should be used to transmit reminders for appointments,
medications, motivational texts, and health education to increase retention in
care. Measures must be taken to reduce risks of privacy intrusion, but these are
not a main obstacle for scaling up systems of this kind.
PMID- 28419150
TI - Disparities in dialysis allocation: An audit from the new South Africa.
AB - End Stage Kidney Disease (ESKD) is a public health problem with an enormous
economic burden. In resource limited settings management of ESKD is often
rationed. Racial and socio-economic inequalities in selecting candidates have
been previously documented in South Africa. New guidelines for dialysis developed
in the Western Cape have focused on prioritizing treatment. With this in mind we
aimed at exploring whether the new guidelines would improve inequalities
previously documented. A retrospective study of patients presented to the
selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD
patients presented between 1 January 2008 and 31 December 2012 were assessed.
Half of the patients came from low socioeconomic areas, and presentation was late
with either overt uremia (n = 181, 44.4%) or fluid overload (n = 179, 43.9%).
More than half (53.9%) of the patients were not selected for the program.
Predictors of non-acceptance onto the program included age above 50 years (OR
0.3, p = 0.001), unemployment (OR 0.3, p<0.001), substance abuse (OR 0.2,
p<0.001), diabetes (OR 0.4, p = 0.016) and a poor psychosocial assessment (OR
0.13, p<0.001). Race, gender and marital status were not predictors. The use of
new guidelines has not led to an increase in inequalities. In view of the
advanced nature of presentation greater efforts need to be made to prevent early
kidney disease, to allocate more resources to renal replacement therapy in view
of the loss of young and potentially productive life.
PMID- 28419151
TI - Skin-resident CD4+ T cells protect against Leishmania major by recruiting and
activating inflammatory monocytes.
AB - Tissue-resident memory T cells are required for establishing protective immunity
against a variety of different pathogens, although the mechanisms mediating
protection by CD4+ resident memory T cells are still being defined. In this study
we addressed this issue with a population of protective skin-resident, IFNgamma
producing CD4+ memory T cells generated following Leishmania major infection. We
previously found that resident memory T cells recruit circulating effector T
cells to enhance immunity. Here we show that resident memory CD4+ T cells mediate
the delayed-hypersensitivity response observed in immune mice and provide
protection without circulating T cells. This protection occurs rapidly after
challenge, and requires the recruitment and activation of inflammatory monocytes,
which limit parasites by production of both reactive oxygen species and nitric
oxide. Overall, these data highlight a novel role for tissue-resident memory
cells in recruiting and activating inflammatory monocytes, and underscore the
central role that skin-resident T cells play in immunity to cutaneous
leishmaniasis.
PMID- 28419152
TI - The disadvantages of being a hybrid during drought: A combined analysis of plant
morphology, physiology and leaf proteome in maize.
AB - A comparative analysis of various parameters that characterize plant morphology,
growth, water status, photosynthesis, cell damage, and antioxidative and
osmoprotective systems together with an iTRAQ analysis of the leaf proteome was
performed in two inbred lines of maize (Zea mays L.) differing in drought
susceptibility and their reciprocal F1 hybrids. The aim of this study was to
dissect the parent-hybrid relationships to better understand the mechanisms of
the heterotic effect and its potential association with the stress response. The
results clearly showed that the four examined genotypes have completely different
strategies for coping with limited water availability and that the inherent
properties of the F1 hybrids, i.e. positive heterosis in morphological parameters
(or, more generally, a larger plant body) becomes a distinct disadvantage when
the water supply is limited. However, although a greater loss of photosynthetic
efficiency was an inherent disadvantage, the precise causes and consequences of
the original predisposition towards faster growth and biomass accumulation
differed even between reciprocal hybrids. Both maternal and paternal parents
could be imitated by their progeny in some aspects of the drought response (e.g.,
the absence of general protein down-regulation, changes in the levels of some
carbon fixation or other photosynthetic proteins). Nevertheless, other features
(e.g., dehydrin or light-harvesting protein contents, reduced chloroplast
proteosynthesis) were quite unique to a particular hybrid. Our study also
confirmed that the strategy for leaving stomata open even when the water supply
is limited (coupled to a smaller body size and some other physiological
properties), observed in one of our inbred lines, is associated with drought
resistance not only during mild drought (as we showed previously) but also during
more severe drought conditions.
PMID- 28419153
TI - Biochemical and structural investigations on phosphoribosylpyrophosphate
synthetase from Mycobacterium smegmatis.
AB - Mycobacterium smegmatis represents one model for studying the biology of its
pathogenic relative Mycobacterium tuberculosis. The structural characterization
of a M. tuberculosis ortholog protein can serve as a valid tool for the
development of molecules active against the M. tuberculosis target. In this
context, we report the biochemical and structural characterization of M.
smegmatis phosphoribosylpyrophosphate synthetase (PrsA), the ortholog of M.
tuberculosis PrsA, the unique enzyme responsible for the synthesis of
phosphoribosylpyrophosphate (PRPP). PRPP is a key metabolite involved in several
biosynthetic pathways including those for histidine, tryptophan, nucleotides and
decaprenylphosphoryl-arabinose, an essential precursor for the mycobacterial cell
wall biosynthesis. Since M. tuberculosis PrsA has been validated as a drug target
for the development of antitubercular agents, the data presented here will add to
the knowledge of the mycobacterial enzyme and could contribute to the development
of M. tuberculosis PrsA inhibitors of potential pharmacological interest.
PMID- 28419154
TI - Salt stress induces changes in the proteomic profile of micropropagated sugarcane
shoots.
AB - Salt stress is one of the most common stresses in agricultural regions worldwide.
In particular, sugarcane is affected by salt stress conditions, and no sugarcane
cultivar presently show high productivity accompanied by a tolerance to salt
stress. Proteomic analysis allows elucidation of the important pathways involved
in responses to various abiotic stresses at the biochemical and molecular levels.
Thus, this study aimed to analyse the proteomic effects of salt stress in
micropropagated shoots of two sugarcane cultivars (CB38-22 and RB855536) using a
label-free proteomic approach. The mass spectrometry proteomics data are
available via ProteomeXchange with identifier PXD006075. The RB855536 cultivar is
more tolerant to salt stress than CB38-22. A quantitative label-free shotgun
proteomic analysis identified 1172 non-redundant proteins, and 1160 of these were
observed in both cultivars in the presence or absence of NaCl. Compared with CB38
22, the RB855536 cultivar showed a greater abundance of proteins involved in non
enzymatic antioxidant mechanisms, ion transport, and photosynthesis. Some
proteins, such as calcium-dependent protein kinase, photosystem I, phospholipase
D, and glyceraldehyde-3-phosphate dehydrogenase, were more abundant in the
RB855536 cultivar under salt stress. Our results provide new insights into the
response of sugarcane to salt stress, and the changes in the abundance of these
proteins might be important for the acquisition of ionic and osmotic homeostasis
during exposure to salt stress.
PMID- 28419155
TI - Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage
degeneration in an experimental rat osteoarthritis model.
AB - Mesenchymal stem cell (MSC)-based cell therapy is a promising avenue for
osteoarthritis (OA) treatment. In the present study, we evaluated the efficacy of
intra-articular injections of culture-expanded allogenic adipose tissue-derived
stem cells (ADSCs) for the treatment of anterior cruciate ligament transection
(ACLT) induced rat OA model. The paracrine effects of major histocompatibility
complex (MHC)-unmatched ADSCs on chondrocytes were investigated in vitro. Rats
were divided into an OA group that underwent ACLT surgery and a sham-operated
group that did not undergo ACLT surgery. Four weeks after surgery mild OA was
induced in the OA group. Subsequently, the OA rats were randomly divided into
ADSC and control groups. A single dose of 1 * 106 ADSCs suspended in 60 MUL
phosphate-buffered saline (PBS) was intra-articularly injected into the rats of
the ADSC group. The control group received only 60 MUL PBS. OA progression was
evaluated macroscopically and histologically at 8 and 12 weeks after surgery.
ADSC treatment did not cause any adverse local or systemic reactions. The
degeneration of articular cartilage was significantly weaker in the ADSC group
compared to that in the control group at both 8 and 12 weeks. Chondrocytes were
co-cultured with MHC-unmatched ADSCs in trans-wells to assess the paracrine
effects of ADSCs on chondrocytes. Co-culture with ADSCs counteracted the IL-1beta
induced mRNA upregulation of the extracellular matrix-degrading enzymes MMP-3 and
MMP-13 and the pro-inflammatory cytokines TNF-alpha and IL-6 in chondrocytes.
Importantly, ADSCs increased the expression of the anti-inflammatory cytokine IL
10 in chondrocytes. The results of this study indicated that the intra-articular
injection of culture-expanded allogenic ADSCs attenuated cartilage degeneration
in an experimental rat OA model without inducing any adverse reactions. MHC
unmatched ADSCs protected chondrocytes from inflammatory factor-induced damage.
The paracrine effects of ADSCs on OA chondrocytes are at least part of the
mechanism by which ADSCs exert their therapeutic activity.
PMID- 28419156
TI - School nurses' attitudes towards and experiences of the Swedish school-based HPV
vaccination programme - A repeated cross sectional study.
AB - The aim was to investigate school nurses' attitudes towards, and experiences of
vaccination against human papillomavirus (HPV), and compare the results with a
similar study three years earlier. School nurses (n = 736) from all counties in
Sweden completed a questionnaire in spring 2016, four years after the
implementation of the national HPV vaccination programme, and three years after
the previous survey. Overall, the school nurses had more favourable attitudes
towards the HPV vaccination programme compared to the study in 2013 (p = 0.015).
More than half of the nurses (n = 415, 56%) strongly agreed that boys should also
be offered the vaccine (p<0.001). There were no differences in school nurses'
perceived knowledge about HPV in order to inform and to answer questions about
the vaccine from the girls or from the parents. More than half of the nurses (n =
409, 56%) reported that they needed more education about HPV. Almost all nurses
(n = 659, 90%) had been contacted by parents with questions about the vaccine,
and most questions were related to vaccine safety. School nurses have a more
favourable attitude towards the vaccination programme against HPV compared to
three years earlier, although almost all nurses had been contacted by parents
with diverse questions and concerns. The nurses believed that they needed more
education about HPV. Thus, it is essential to provide ongoing education and
training for school nurses who are key healthcare professionals for providing
information about HPV and HPV vaccination to parents and to pupils.
PMID- 28419157
TI - The analysis of viability for mammalian cells treated at different temperatures
and its application in cell shipment.
AB - Mammalian cells are very important experimental materials and widely used in
biological and medical research fields. It is often required that mammalian cells
are transported from one laboratory to another to meet with various researches.
Conventional methods for cell shipment are laborious and costive despite of
maintaining high viability. In this study we aimed to develop a simple and low
cost method for cell shipment by investigating the viabilities of different cell
lines treated at different temperatures. We show that the viability of mammalian
cells incubated at 1 degrees C or 5 degrees C significantly reduced when compared
with that at 16 degrees C or 22 degrees C. Colony formation assays revealed that
preservation of mammalian cells at 1 degrees C or 5 degrees C led to a poorer
recovery than that at 16 degrees C or 22 degrees C. The data from proliferation
and apoptotic assays confirmed that M2 cells could continue to proliferate at 16
degrees C or 22 degrees C, but massive death was caused by apoptosis at 1 degrees
C or 5 degrees C. The morphology of mammalian cells treated under hypothermia
showed little difference from that of the untreated cells. Quantitative RT-PCR
and alkaline phosphatase staining confirmed that hypothermic treatment did not
change the identity of mouse embryonic stem cells. A case study showed that
mammalian cells directly suspended in culture medium were able to be shipped for
long distance and maintained a high level of viability and recovery. Our findings
not only broaden the understanding to the effect of hypothermia on the viability
of mammalian cells, but also provide an alternative approach for cell shipment.
PMID- 28419158
TI - Identification of pre-fertilization reproductive barriers and the underlying
cytological mechanism in crosses among three petal-types of Jasminum sambac and
their relevance to phylogenetic relationships.
AB - Crosses among single-, double- and multi-petal jasmine cultivars (Jasminum sambac
Aiton) are unable to easily generate hybrids. To identify the reproductive
barriers restricting hybrid set, dynamic changes in jasmine pollen viability and
pistil receptivity were compared at different flowering stages. Pollen-pistil
interactions in six reciprocal crosses were also investigated to characterize
pollen-stigma compatibility. Additionally, paraffin sections of pollinated embryo
sacs were prepared for subsequent analyses of developmental status. Furthermore,
pistil cell ultrastructural characteristics were observed to reveal cytological
mechanism regulating pistil receptivity and the pollen-pistil interactions. We
observed that pollen viability and stigma receptivity varied depending on petal
phenotype and flowering stage and were easily lost during flowering. Different
reciprocal crosses exhibited varied pollen-stigma compatibilities according to
the pollen germination rates. Although some pollen grains germinated normally on
maternal stigmas, the pollen tubes were arrested in the pistils and were unable
to reach the ovaries. Additionally, the embryo sacs remained unfertilized until
degenerating. Therefore, jasmine crosses are affected by pre-fertilization
reproductive barriers. Low pollen fertility and poor stigma receptivity are
detrimental to pollen germination and pollen-pistil compatibility, indicating
they are two factors affecting hybrid set. Ultrastructural observation of the
pistil cells revealed that cell death occurred during flowering. Thus, the early
and rapid senescence of pistils is likely responsible for the decreased pistil
receptivity and inhibited pollen tube growth. These findings may be relevant for
future jasmine hybridizations. They provide new insights for the development of
methods to overcome reproductive barriers and may also be useful for clarifying
the phylogenetic relationships among jasmine cultivars with differing petal
phenotypes.
PMID- 28419159
TI - Oral potassium supplementation for management of essential hypertension: A meta
analysis of randomized controlled trials.
AB - IMPORTANCE: Increased dietary potassium intake is thought to be associated with
low blood pressure (BP). Whether potassium supplementation may be used as an
antihypertensive agent is a question that should be answered. OBJECTIVE: To
assess the effect of oral potassium supplementation on blood pressure in patients
with primary hypertension. SEARCH METHODS: We searched Medline, Web of Science,
Scopus, Cochrane Central Register of Controlled Trials until October 2016. We
also screened reference lists of articles and previous reviews. We applied no
language restrictions. SELECTION CRITERIA: We included randomized placebo
controlled clinical trials addressing the effect of potassium supplementation on
primary hypertension for a minimum of 4 weeks. DATA COLLECTION AND ANALYSIS: We
extracted data on systolic and diastolic BP (SBP and DBP) at the final follow-up.
We explored the heterogeneity across studies using Cochran's test and I2
statistic and assessed the probability of publication bias using Begg's and
Egger's tests. We reported the mean difference (MD) of SBP and DBP in a random
effects model. RESULTS: We found a total of 9059 articles and included 23 trials
with 1213 participants. Compared to placebo, potassium supplementation resulted
in modest but significant reductions in both SBP (MD -4.25 mmHg; 95% CI: -5.96 to
-2.53; I2 = 41%) and DBP (MD -2.53 mmHg; 95% CI: -4.05 to -1.02; I2 = 65%).
According to the change-score analysis, based on 8 out of 23 trials, compared to
baseline, the mean changes in SBP (MD -8.89 mmHg; 95% CI: -13.67 to -4.11) and
DBP (MD -6.42 mmHg; 95% CI: -10.99 to -1.84) was significantly higher in the
intervention group than the control group. CONCLUSIONS: Our findings indicated
that potassium supplementation is a safe medication with no important adverse
effects that has a modest but significant impact BP and may be recommended as an
adjuvant antihypertensive agent for patients with essential hypertension.
PMID- 28419160
TI - An empirically grounded agent based model for modeling directs, conflict
detection and resolution operations in air traffic management.
AB - We present an agent based model of the Air Traffic Management socio-technical
complex system aiming at modeling the interactions between aircraft and air
traffic controllers at a tactical level. The core of the model is given by the
conflict detection and resolution module and by the directs module. Directs are
flight shortcuts that are given by air controllers to speed up the passage of an
aircraft within a certain airspace and therefore to facilitate airline
operations. Conflicts between flight trajectories can occur for two main reasons:
either the planning of the flight trajectory was not sufficiently detailed to
rule out all potential conflicts or unforeseen events during the flight require
modifications of the flight plan that can conflict with other flight
trajectories. Our model performs a local conflict detection and resolution
procedure. Once a flight trajectory has been made conflict-free, the model
searches for possible improvements of the system efficiency by issuing directs.
We give an example of model calibration based on real data. We then provide an
illustration of the capability of our model in generating scenario simulations
able to give insights about the air traffic management system. We show that the
calibrated model is able to reproduce the existence of a geographical
localization of air traffic controllers' operations. Finally, we use the model to
investigate the relationship between directs and conflict resolutions (i) in the
presence of perfect forecast ability of controllers, and (ii) in the presence of
some degree of uncertainty in flight trajectory forecast.
PMID- 28419161
TI - Unidentifiable by morphology: DNA barcoding of plant material in local markets in
Iran.
AB - Local markets provide a rapid insight into the medicinal plants growing in a
region as well as local traditional health concerns. Identification of market
plant material can be challenging as plants are often sold in dried or processed
forms. In this study, three approaches of DNA barcoding-based molecular
identification of market samples are evaluated, two objective sequence matching
approaches and an integrative approach that coalesces sequence matching with a
priori and a posteriori data from other markers, morphology, ethnoclassification
and species distribution. Plant samples from markets and herbal shops were
identified using morphology, descriptions of local use, and vernacular names with
relevant floras and pharmacopoeias. DNA barcoding was used for identification of
samples that could not be identified to species level using morphology. Two
methods based on BLAST similarity-based identification, were compared with an
integrative identification approach. Integrative identification combining the
optimized similarity-based approach with a priori and a posteriori information
resulted in a 1.67, 1.95 and 2.00 fold increase for ITS, trnL-F spacer, and both
combined, respectively. DNA barcoding of traded plant material requires objective
strategies to include data from multiple markers, morphology, and traditional
knowledge to optimize species level identification success.
PMID- 28419162
TI - Symmetry based assembly of a 2 dimensional protein lattice.
AB - The design of proteins that self-assemble into higher order architectures is of
great interest due to their potential application in nanotechnology.
Specifically, the self-assembly of proteins into ordered lattices is of special
interest to the field of structural biology. Here we designed a 2 dimensional
(2D) protein lattice using a fusion of a tandem repeat of three TelSAM domains
(TTT) to the Ferric uptake regulator (FUR) domain. We determined the structure of
the designed (TTT-FUR) fusion protein to 2.3 A by X-ray crystallographic methods.
In agreement with the design, a 2D lattice composed of TelSAM fibers
interdigitated by the FUR domain was observed. As expected, the fusion of a
tandem repeat of three TelSAM domains formed 21 screw axis, and the self-assembly
of the ordered oligomer was under pH control. We demonstrated that the fusion of
TTT to a domain having a 2-fold symmetry, such as the FUR domain, can produce an
ordered 2D lattice. The TTT-FUR system combines features from the rotational
symmetry matching approach with the oligomer driven crystallization method. This
TTT-FUR fusion was amenable to X-ray crystallographic methods, and is a promising
crystallization chaperone.
PMID- 28419163
TI - Response of microbial community of organic-matter-impoverished arable soil to
long-term application of soil conditioner derived from dynamic rapid fermentation
of food waste.
AB - Rapid fermentation of food waste can be used to prepare soil conditioner. This
process consumes less time and is more cost-effective than traditional
preparation technology. However, the succession of the soil microbial community
structure after long-term application of rapid fermentation-derived soil
conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food
waste was performed to develop a soil conditioner and the successions and
diversity of bacterial communities in an organic-matter-impoverished arable soil
after six years of application of DRF-derived soil conditioner were investigated.
Results showed that the treatment increased soil organic matter (SOM)
accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively.
Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant
phyla, occupying 65.95%-77.52% of the bacterial sequences. Principal component
analysis (PCA) results showed that the soil bacterial communities were largely
influenced by the treatment. Redundancy analysis (RDA) results showed that the
relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia,
Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP,
NH4+-N, NO3--N, OM, and moisture. These communities were all distributed in the
soil samples collected in the sixth year of application. Long-term treatment did
not enhance the diversity of bacterial species but significantly altered the
distribution of major functional bacterial communities in the soils. Application
of DRF-derived soil conditioner could improve the soil quality and optimize the
microbial community, ultimately enhancing fruit yields.
PMID- 28419164
TI - Population pharmacokinetic modelling of rupatadine solution in 6-11 year olds and
optimisation of the experimental design in younger children.
AB - AIMS: To optimise a pharmacokinetic (PK) study design of rupatadine for 2-5 year
olds by using a population PK model developed with data from a study in 6-11 year
olds. The design optimisation was driven by the need to avoid children's
discomfort in the study. METHODS: PK data from 6-11 year olds with allergic
rhinitis available from a previous study were used to construct a population PK
model which we used in simulations to assess the dose to administer in a study in
2-5 year olds. In addition, an optimal design approach was used to determine the
most appropriate number of sampling groups, sampling days, total samples and
sampling times. RESULTS: A two-compartmental model with first-order absorption
and elimination, with clearance dependent on weight adequately described the PK
of rupatadine for 6-11 year olds. The dose selected for a trial in 2-5 year olds
was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study
design consisted of four groups of children (10 children each), a maximum
sampling window of 2 hours in two clinic visits for drawing three samples on day
14 and one on day 28 coinciding with the final examination of the study.
CONCLUSIONS: A PK study design was optimised in order to prioritise avoidance of
discomfort for enrolled 2-5 year olds by taking only four blood samples from each
child and minimising the length of hospital stays.
PMID- 28419165
TI - Soaking suggests "alternative facts": Only co-crystallization discloses major
ligand-induced interface rearrangements of a homodimeric tRNA-binding protein
indicating a novel mode-of-inhibition.
AB - For the efficient pathogenesis of Shigella, the causative agent of bacillary
dysentery, full functionality of tRNA-guanine transglycosylase (TGT) is
mandatory. TGT performs post-transcriptional modifications of tRNAs in the
anticodon loop taking impact on virulence development. This suggests TGT as a
putative target for selective anti-shigellosis drug therapy. Since bacterial TGT
is only functional as homodimer, its activity can be inhibited either by blocking
its active site or by preventing dimerization. Recently, we discovered that in
some crystal structures obtained by soaking the full conformational adaptation
most likely induced in solution upon ligand binding is not displayed. Thus,
soaked structures may be misleading and suggest irrelevant binding modes.
Accordingly, we re-investigated these complexes by co-crystallization. The
obtained structures revealed large conformational rearrangements not visible in
the soaked complexes. They result from spatial perturbations in the ribose
34/phosphate-35 recognition pocket and, consequently, an extended loop-helix
motif required to prevent access of water molecules into the dimer interface
loses its geometric integrity. Thermodynamic profiles of ligand binding in
solution indicate favorable entropic contributions to complex formation when
large conformational adaptations in the dimer interface are involved. Native MS
titration experiments reveal the extent to which the homodimer is destabilized in
the presence of each inhibitor. Unexpectedly, one ligand causes a complete
rearrangement of subunit packing within the homodimer, never observed in any
other TGT crystal structure before. Likely, this novel twisted dimer is
catalytically inactive and, therefore, suggests that stabilizing this non
productive subunit arrangement may be used as a further strategy for TGT
inhibition.
PMID- 28419166
TI - Comparison of standardized uptake value of 18F-FDG-PET-CT with 21-gene recurrence
score in estrogen receptor-positive, HER2-negative breast cancer.
AB - BACKGROUND: We investigated the relationship between 18F-fluorodeoxyglucose
positron emission tomography-computed tomography (18F-FDG-PET-CT) standardized
uptake value (SUV) and 21-gene recurrence score (RS) in estrogen receptor (ER)
positive/HER2-negative breast cancer. MATERIALS AND METHODS: One hundred sixty
seven patients were identified among those who underwent preoperative 18F-FDG-PET
CT and had RS. Maximum SUV was obtained from 18F-FDG-PET-CT; the cut-off point
was 4. RESULTS: The continuous RS and SUV correlated positively (Pearson's R =
0.555; P < 0.001). An inverse correlation was found between progesterone receptor
(PR) expression by reverse transcriptase-polymerase chain reaction, and SUV
(Pearson's R = -0.408; P < 0.001). Good agreement between dichotomized RS (<26
vs. >=26) and SUV (<4 vs. >=4) was observed in 137 of 167 patients (82.0%; 95%
confidence interval [CI], 76.2-87.9). Among patients with low SUV, 114 of 115
(99.1% [95% CI, 97.4-100.0]) had tumors with lower RS (<26). Although 23 of 52
women (44.2% [95% CI, 30.7-57.7]) with high SUV had higher RS (>=26), all 13
women with high RS (>=31) had high-SUV tumors. Most cases with disagreements
between SUV and RS (n = 30) were classified as high SUV/lower RS (n = 29). The
discordant group had higher grade or elevated Ki67 expression (>=20%) compared
with the low SUV/lower RS group (n = 109), but higher PR expression compared with
the high SUV/higher RS group (n = 23). Multiple logistic regression analysis
showed that high SUV were associated with higher RS (>=26). CONCLUSIONS: SUV, as
a biologic parameter represented using a continuous variable, was found to
associate with RS in ER-positive, HER2-negative breast cancer. Further studies
may reveal the biology underlying the discordance between the markers.
PMID- 28419167
TI - Pharmacy students' anxiety towards research during their undergraduate degree;
How to reduce it?
AB - OBJECTIVE: To measure pharmacy students' anxiety towards research and how
academic support, academic effort, attitude and self-efficacy influence their
research anxiety. METHODS: A cross-sectional study was conducted with
undergraduate final year students of pharmacy using a convenient sampling method.
A validated self-administered questionnaire was used. RESULTS: Response rate for
this study was 85.9% (128 students from a population of 149). The participants
agreed that they read literature to understand research, but did not attend
research-related coursework. Most participants (91.4%) felt that they were under
stress while doing research. Almost all participants (97.6%) felt that they were
doing very badly during their data analysis or they may fail their research
projects. The majority of participants agreed that help from the lecturers' and
friends in research give emotional support for their research activities.
CONCLUSION: Academic support for pharmacy students, along with their additional
academic effort will improve the students' self-efficacy and reduce research
anxiety.
PMID- 28419168
TI - Dynamic patterns of expression for genes regulating cytokinin metabolism and
signaling during rice inflorescence development.
AB - Inflorescence development in cereals, including such important crops as rice,
maize, and wheat, directly affects grain number and size and is a key determinant
of yield. Cytokinin regulates meristem size and activity and, as a result, has
profound effects on inflorescence development and architecture. To clarify the
role of cytokinin action in inflorescence development, we used the NanoString
nCounter system to analyze gene expression in the early stages of rice panicle
development, focusing on 67 genes involved in cytokinin biosynthesis,
degradation, and signaling. Results point toward key members of these gene
families involved in panicle development and indicate that the expression of many
genes involved in cytokinin action differs between the panicle and vegetative
tissues. Dynamic patterns of gene expression suggest that subnetworks mediate
cytokinin action during different stages of panicle development. The variation of
expression during panicle development is greater among genes encoding proteins
involved in cytokinin metabolism and negative regulators of the pathway than for
the genes in the primary response pathway. These results provide insight into the
expression patterns of genes involved in cytokinin action during inflorescence
development in a crop of agricultural importance, with relevance to similar
processes in other monocots. The identification of subnetworks of genes expressed
at different stages of early panicle development suggests that manipulation of
their expression could have substantial effects on inflorescence architecture.
PMID- 28419169
TI - Decomposing functional trait associations in a Chinese subtropical forest.
AB - Functional traits, properties of organisms correlated with ecological
performance, play a central role in plant community assembly and functioning. To
some extents, functional traits vary in concert, reflecting fundamental
ecological strategies. While "trait syndromes" characteristic of e.g. fast
growing, early-successional vs. competitive, late-successional species are
recognized in principle, less is known about the environmental and genetic
factors at the source of trait variation and covariation within plant
communities. We studied the three leaf traits leaf half-life (LHL), leaf mass per
area (LMA) and nitrogen concentration in green leaves (Ngreen) and the wood trait
wood density (WD) in 294 individuals belonging to 45 tree or shrub species in a
Chinese subtropical forest from September 2006 to January 2009. Using multilevel
ANOVA and decomposition of sums of products, we estimated the amount of trait
variation and covariation among species (mainly genetic causes), i.e. plant
functional type (deciduous vs. evergreen species), growth form (tree vs. shrub
species), family/genus/species differences, and within species (mainly
environmental causes), i.e. individual and season. For single traits, the
variation between functional types and among species within functional types was
large, but only LMA and Ngreen varied significantly among families and thus
showed phylogenetic signal. Trait variation among individuals within species was
small, but large temporal variation due to seasonal effects was found within
individuals. We did not find any trait variation related to soil conditions
underneath the measured individuals. For pairs of traits, variation between
functional types and among species within functional types was large, reflecting
a strong evolutionary coordination of the traits, with LMA, LHL and WD being
positively correlated among each other and negatively with Ngreen. This
integration of traits was consistent with a putative stem-leaf economics spectrum
ranging from deciduous species with thin, high-nitrogen leaves and low-density
wood to evergreen species with thick, low-nitrogen leaves and dense wood and was
not influenced by phylogenetic history. Trait coordination within species was
weak, allowing individual trees to deviate from the interspecific trait
coordination and thus respond flexibly to environmental heterogeneity. Our
findings suggest that within a single woody plant community variation and
covariation in functional traits allows a large number of species to co-exist and
cover a broad spectrum of multivariate niche space, which in turn may increase
total resource extraction by the community and community functioning.
PMID- 28419170
TI - Evaluation of the relative efficacy of a couple cognitive-behaviour therapy (CBT)
for Premenstrual Disorders (PMDs), in comparison to one-to-one CBT and a wait
list control: A randomized controlled trial.
AB - DESIGN: A randomised control trial (RCT) was conducted to examine the efficacy of
couple-based cognitive behaviour therapy (CBT) for Premenstrual Disorders (PMDs),
in comparison to one-to-one CBT and a wait-list control. METHODS: Triangulation
of quantitative and qualitative outcome measures evaluated changes pre-post
intervention. Eighty three women were randomly allocated across three conditions,
with 63 completing post-intervention measures, a retention rate of 76%. RESULTS:
Repeated measures analysis of variance found a significant time by group
interaction identifying that women in the two CBT conditions reported lower total
premenstrual symptoms, emotional reactivity/mood, and premenstrual distress, in
comparison to the wait list control. Significantly higher active behavioural
coping post-intervention was found in the couple condition than in the one-to-one
and wait list control groups. Qualitative analysis provided insight into the
subjective experience of PMDs and participation in the intervention study. Across
groups, women reported increased awareness and understanding of premenstrual
change post-intervention. A larger proportion of women in the CBT conditions
reported reduction in intensity and frequency of negative premenstrual emotional
reactivity, increased communication and help-seeking, increased understanding and
acceptance of embodied change, and the development of coping skills, post
intervention. Increased partner understanding and improved relationship post
intervention was reported by a greater proportion of participants in the CBT
conditions, most markedly in the couple condition. CONCLUSION: These findings
suggest that one-to-one and couple CBT interventions can significantly reduce
women's premenstrual symptomatology and distress, and improve premenstrual
coping. Couple based CBT interventions may have a greater positive impact upon
behavioural coping and perceptions of relationship context and support. This
suggests that CBT should be available for women reporting moderate-severe PMDs,
with couple-based CBT offering additional benefits to a one-to-one modality.
PMID- 28419171
TI - Ultrasound texture analysis: Association with lymph node metastasis of papillary
thyroid microcarcinoma.
AB - This retrospective study aimed to evaluate whether ultrasound texture analysis is
useful to predict lymph node metastasis in patients with papillary thyroid
microcarcinoma (PTMC). This study was approved by the Institutional Review Board,
and the need to obtain informed consent was waived. Between May and July 2013,
361 patients (mean age, 43.8 +/- 11.3 years; range, 16-72 years) who underwent
staging ultrasound (US) and subsequent thyroidectomy for conventional PTMC <= 10
mm between May and July 2013 were included. Each PTMC was manually segmented and
its histogram parameters (Mean, Standard deviation, Skewness, Kurtosis, and
Entropy) were extracted with Matlab software. The mean values of histogram
parameters and clinical and US features were compared according to lymph node
metastasis using the independent t-test and Chi-square test. Multivariate
logistic regression analysis was performed to identify the independent factors
associated with lymph node metastasis. Tumors with lymph node metastasis (n =
117) had significantly higher entropy compared to those without lymph node
metastasis (n = 244) (mean+/-standard deviation, 6.268+/-0.407 vs. 6.171+/
.0.405; P = .035). No additional histogram parameters showed differences in mean
values according to lymph node metastasis. Entropy was not independently
associated with lymph node metastasis on multivariate logistic regression
analysis (Odds ratio, 0.977 [95% confidence interval (CI), 0.482-1.980]; P =
.949). Younger age (Odds ratio, 0.962 [95% CI, 0.940-0.984]; P = .001) and lymph
node metastasis on US (Odds ratio, 7.325 [95% CI, 3.573-15.020]; P < .001) were
independently associated with lymph node metastasis. Texture analysis was not
useful in predicting lymph node metastasis in patients with PTMC.
PMID- 28419172
TI - Enhanced disease resistance and drought tolerance in transgenic rice plants
overexpressing protein elicitors from Magnaporthe oryzae.
AB - Exogenous application of the protein elicitors MoHrip1 and MoHrip2, which were
isolated from the pathogenic fungus Magnaporthe oryzae (M. oryzae), was
previously shown to induce a hypersensitive response in tobacco and to enhance
resistance to rice blast. In this work, we successfully transformed rice with the
mohrip1 and mohrip2 genes separately. The MoHrip1 and MoHrip2 transgenic rice
plants displayed higher resistance to rice blast and stronger tolerance to
drought stress than wild-type (WT) rice and the vector-control pCXUN rice. The
expression of salicylic acid (SA)- and abscisic acid (ABA)-related genes was also
increased, suggesting that these two elicitors may trigger SA signaling to
protect the rice from damage during pathogen infection and regulate the ABA
content to increase drought tolerance in transgenic rice. Trypan blue staining
indicated that expressing MoHrip1 and MoHrip2 in rice plants inhibited hyphal
growth of the rice blast fungus. Relative water content (RWC), water usage
efficiency (WUE) and water loss rate (WLR) were measured to confirm the high
capacity for water retention in transgenic rice. The MoHrip1 and MoHrip2
transgenic rice also exhibited enhanced agronomic traits such as increased plant
height and tiller number.
PMID- 28419173
TI - Sponge symbioses between Xestospongia deweerdtae and Plakortis spp. are not
motivated by shared chemical defense against predators.
AB - The recently described epizoic sponge-sponge symbioses between Xestospongia
deweerdtae and two species of Plakortis present an unusual series of sponge
interactions. Sponges from the genus Plakortis are fierce allelopathic
competitors, rich in cytotoxic secondary metabolites, and yet X. deweerdtae
flourishes as an epizoic encrustation on Plakortis deweerdtaephila and Plakortis
symbiotica. Our objective in this study was to evaluate the hypothesis that X.
deweerdtae grows epizoic to these two species of Plakortis due to a shared
chemical defense against predators. We collected free-living individuals of X.
deweerdtae and symbiotic pairs from a wide geographical range to generate crude
organic extracts and a series of polarity fractions from sponge extract. We
tested the deterrency of these extracts against three common coral reef
predators: the bluehead wrasse, Thalassoma bifasciatum, the Caribbean sharpnose
puffer, Canthigaster rostrata, and the white spotwrist hermit crab, Pagurus
criniticornis. While the chemical defenses of P. deweerdtaephila and P.
symbiotica are more potent than those of X. deweerdtae, all of the sponge species
we tested significantly deterred feeding in all three generalist predators. The
free-living form of X. deweerdtae is mostly defended across the region, with a
few exceptions. The associated form of X. deweerdtae is always defended, and both
species of Plakortis are very strongly defended, with puffers refusing to consume
extract-treated pellets until the extract was diluted to 1/256* concentration.
Using diode-array high performance liquid chromatography (HPLC) coupled with high
resolution mass spectrometry (LC-MS/IT-TOF), we found two secondary metabolites
from P. deweerdtaephila, probably the cyclic endoperoxides plakinic acid I and
plakinic acid K, in low concentrations in the associated-but not the free-living
form of X. deweerdtae, suggesting a possible translocation of defensive chemicals
from the basibiont to the epibiont. Comparing the immense deterrency of Plakortis
spp. extracts to the extracts of X. deweerdtae gives the impression that there
may be some sharing of chemical defenses: one partner in the symbiosis is clearly
more defended than the other and a small amount of its defensive chemistry may
translocate to the partner. However, X. deweerdtae effectively deters predators
with its own defensive chemistry. Multiple lines of evidence provide no support
for the shared chemical defense hypothesis. Given the diversity of other
potential food resources available to predators on coral reefs, it is improbable
that the evolution of these specialized sponge-sponge symbioses has been driven
by predation pressure.
PMID- 28419174
TI - Stronger diversity effects with increased environmental stress: A study of
multitrophic interactions between oak, powdery mildew and ladybirds.
AB - Recent research has suggested that increasing neighbourhood tree species
diversity may mitigate the impact of pests or pathogens by supporting the
activities of their natural enemies and/or reducing the density of available
hosts. In this study, we attempted to assess these mechanisms in a multitrophic
study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe
spp.) and a mycophagous ladybird (Psyllobora vigintiduopunctata). We assessed
ladybird mycophagy on oak PM in function of different neighbourhood tree species
compositions. We also evaluated whether these species interactions were modulated
by environmental conditions as suggested by the Stress Gradient Hypothesis. We
adopted a complementary approach of a field experiment where we monitored oak
saplings subjected to a reduced rainfall gradient in a young planted forest
consisting of different tree species mixtures, as well as a lab experiment where
we independently evaluated the effect of different watering treatments on PM
infections and ladybird mycophagy. In the field experiment, we found effects of
neighbourhood tree species richness on ladybird mycophagy becoming more positive
as the target trees received less water. This effect was only found as weather
conditions grew drier. In the lab experiment, we found a preference of ladybirds
to graze on infected leaves from trees that received less water. We discuss
potential mechanisms that might explain this preference, such as emissions of
volatile leaf chemicals. Our results are in line with the expectations of the
Natural Enemies Hypothesis and support the hypothesis that biodiversity effects
become stronger with increased environmental stress.
PMID- 28419175
TI - Talent identification and recruitment in youth soccer: Recruiter's perceptions of
the key attributes for player recruitment.
AB - Using the modified Delphi method, we aimed to understand the attributes youth
coaches and recruiters perceive as important when identifying skilled youth
performance at the entry level of representative soccer in Australia (i.e., Under
13 years). Furthermore, we also aimed to describe the current methods youth
coaches and recruiters use to assess and identify these attributes in youth
players. Australian regional youth technical directors and coaches (n = 20)
completed a three stage process, including an initial interview and two
subsequent questionnaires, whereby attributes and qualities associated with
talent identification were rated and justified according to the importance for
youth player performance and talent identification. Results indicate a hierarchy
of attributes recruiters perceive as important for Under 13 soccer performance,
including technical (i.e., first touch, striking the ball, one-versus-one
ability, and technical ability under pressure), tactical (i.e., decision-making
ability) and psychological attributes (i.e., coachability and positive attitude).
In addition, the findings indicated attributes and qualities not emphasised
within the talent identification process including, physiological,
anthropometrical, sociological and several psychological attributes. It is
suggested talent recruiters apply a holistic multidisciplinary approach to talent
identification, with the current findings potentially providing initial evidence
to suggest recruiters do consider numerous attributes when selecting and
identifying youth players.
PMID- 28419176
TI - MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant
candidates in southern Brazil.
AB - The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is
located centromerically to the human leukocyte antigen (HLA)-B. The short
distance between these loci in the MHC indicates the presence of linkage
disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and
this polymorphism has not been well documented in different populations. In this
study, we estimated the allelic frequencies of MICA and the linkage
disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern
Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence
specific primer method (PCR-SSO), combined with the Luminex technology. A total
of 19 MICA allele groups were identified. The most frequent allele groups were
MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common
haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35
(5.63%). As expected from the proximity of the MICA and HLA-B loci, most
haplotypes showed strong LD. Renal patients and healthy subjects in the same
region of Brazil showed statistically significant differences in their MICA
polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc
= 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was
more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469).
This study provided information on the distribution of MICA polymorphisms and
linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant
candidates. This information should help to determine the mechanisms of
susceptibility to different diseases in patients with chronic kidney disease, and
to elucidate the mechanisms involved in allograft rejection associated with MICA
polymorphisms in a Brazilian population.
PMID- 28419177
TI - Interpreting Patterns of Low Scores on the NIH Toolbox Cognition Battery.
AB - Introduction: The National Institutes of Health Toolbox for Assessment of
Neurological and Behavioral Function Cognition Battery is comprised of seven
cognitive tests, including two tests measuring crystallized cognitive ability
(i.e., vocabulary and reading) and five tests measuring fluid cognitive
functioning (i.e., working memory, memory, speed of processing, and executive
functioning). This study presents comprehensive base rate tables for the
frequency of low scores in adults and older adults from the normative sample.
Methods: Participants were 843 adults, ages 20-85, from the NIH Toolbox
standardization sample who completed all seven cognition tests. Rates of low
scores were derived for standard age-adjusted and fully-demographically-adjusted
scores at multiple cut-scores. Base rates were stratified by education,
crystallized intellectual ability, and cognitive domain. Results: Using the five
demographically-adjusted fluid cognitive test scores, 45.9% of adults obtained
one or more scores at or below the 16th percentile, and 16.8% obtained one or
more score at or below the 5th percentile, which is consistent with findings from
other neurocognitive test batteries. Discussion: Based on the study findings,
nearly 50% of adults in the general population would meet psychometric criteria
for a diagnosis of the Diagnostic and Statistical Manual of Mental Disorders
Fifth Edition (DSM-5) Mild Neurocognitive Disorder (MND). We developed new
psychometric criteria for identifying MND using the NIH Toolbox Cognition Battery
that reduce the false positive rate. Knowing these multivariate normative base
rates will help researchers and clinicians interpret NIH Toolbox scores in people
with neurodevelopmental, psychiatric, medical, neurological, and
neurodegenerative disorders that affect cognitive functioning.
PMID- 28419178
TI - Acquiring evidence for precision prostate cancer care.
PMID- 28419179
TI - The Intensity of Brief Interventions in Patients with Acute Alcoholic
Pancreatitis Should be Increased, Especially in Young Patients with Heavy Alcohol
Consumption.
AB - Aims: After the first acute alcoholic pancreatitis (AAP), active repeated brief
interventions (BIs) have been shown to protect against recurrent acute
pancreatitis (RAP). However, in daily hospital practice the treatment of alcohol
problems varies. Our aim was to study BIs performed in the clinic during AAP and
whether this prevents from future RAP episodes. Methods: Data on all patients
discharged between 10/2010 and 10/2012 with acute pancreatitis as the primary
diagnosis were obtained from the hospital database. Patients with the first
attack of AAP were included in the study. Documented BIs during hospitalization
for AAP and RAP and the development of RAP and chronic pancreatitis during median
(range) follow-up of 4.2 (0.2-6.1) years were analyzed. Patients were also
contacted with a mailed questionnaire. Results: A total of 74 patients with first
AAP during the study period were included. Of these, 32% developed RAP during
follow-up. Of the patients, 72% received a documented BI during initial
hospitalization, with no difference between patients who later did or did not
develop RAP (71 vs. 72%; ns). Younger age (OR = 0.96, 95% CI = 0.92-1.00) and
higher AUDIT points (P = 0.044; OR = 5.6; 95% CI = 1.02-30.9 for >=20 AUDIT
points) were associated with RAP. AUDIT test had 70% sensitivity and 71%
specificity at a cut-off value of 20 points for predicting RAP. Conclusions: Only
72% of the patients received a documented BI during the initial hospitalization
for AAP. The in-hospital BI as such did not prevent the development of RAP. Young
patients with AUDIT points >=20 are especially at high risk for developing RAP
and should be included in a more intense follow-up care program to maximize
prevention. Short summary: During hospitalization for acute alcoholic
pancreatitis (AAP), one third of the patients did not receive brief interventions
(BIs). The in-hospital BI by itself was not sufficient enough to prevent disease
recurrence in follow-up of 4 years. Young age and higher AUDIT-points were
significant risk factors for recurrent attacks of AAP.
PMID- 28419180
TI - Impact of gestational nicotine exposure on intrauterine and fetal infection in a
rodent model.
AB - We investigated the interaction between prenatal nicotine exposure and
intrauterine infection using established rat models. Beginning at gestation day
(GD) 6, dams were continuously infused with either saline or 6 mg/kg/day nicotine
(Nic). At GD 14, dams received either sterile broth or 105 colony-forming units
Mycoplasma pulmonis (MP), resulting in four treatment groups: control (4 dams, 33
fetal units); MP only (5 dams, 55 fetal units); Nic only (5 dams, 61 fetal
units), and Nic + MP (7 dams, 82 fetal units). At GD 18, nicotine exposure
significantly increased (P <= 0.02) the percentage of amniotic fluids and fetuses
infected by MP but did not impact colonization rates of maternal sites. Nicotine
exposure significantly reduced the numbers of MP in the placenta required for
high microbial loads (>=104 color-changing units) in the amniotic fluid (P <
0.01). Fetal inflammatory response lesions were most extensive in the Nic only
and Nic + MP groups (P < 0.0001). Control and MP only placentas were interleukin
(IL)10-dominant, consistent with an M2/Th2 environment. Placentas exposed to
nicotine shifted to a neutral environment, with equivalent levels of interferon
gamma (IFNG) and IL10. Both IL6 and tumor necrosis factor (TNF) levels in
amniotic fluid were highly elevated when both nicotine and infection were
present. Our study suggests that prenatal exposure to nicotine increases the risk
for intrauterine infection, lowers the infectious dose required to breach the
placental barrier and infect the amniotic fluid and fetus, and alters the
pathology and inflammatory profile associated with maternal and fetal sites.
PMID- 28419181
TI - Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or
metastatic head and neck squamous cell carcinoma.
AB - Background: Pembrolizumab and nivolumab are immune checkpoint inhibitors
targeting PD-1 that have recently been approved in pretreated recurrent and/or
metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the
clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents
but rather to experience an acceleration of tumor growth kinetics (TGK). Patients
and methods: We retrospectively compared TGK on immunotherapy and TGK on last
treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four
French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before
treatment and the slope of tumor growth on treatment) was calculated.
Hyperprogression was defined as a TGKR >= 2. Results: From September 2012 to
September 2015, 34 patients were identified. Patterns of recurrence included
exclusive loco-regional recurrence in 14 patients, exclusive distant metastases
in 11 patients, and both in 9 patients. No pseudo-progression was observed.
Hyperprogression was observed in 10 patients (29%), including 9 patients with at
least a locoregional recurrence, and only 1 patient with exclusively distant
metastases. Hyperprogression significantly correlated with a regional recurrence
(TGKR >= 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant
recurrence. Hyperprogression was associated with a shorter progression-free
survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not
with overall survival (P = 0.77). Conclusions: Hyperprogression was observed in
29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated
with a shorter PFS. It occurred in 39% of patients with at least a locoregional
recurrence and 9% of patients with exclusively distant metastases. No pseudo
progressions were reported. Mechanisms and causality of hyperprogression should
further be assessed through prospective controlled studies.
PMID- 28419182
TI - Molecular classification of pulmonary sarcomatoid carcinomas suggests new
therapeutic opportunities.
AB - Background: Pulmonary sarcomatoid carcinoma (SC) is a rare disease with poor
prognosis and with strong inter- and intratumor heterogeneity. However, molecular
classification is currently focused on activating MET mutations. We sought to
better characterize the molecular diversity of SC using mutational signatures
that reflect different mutational processes, such as tobacco-associated adducts
(signature 4), BRCA1/BRCA2 deficiency (signature 3), or APOBEC enzyme deamination
(signatures 2 and 13). Patients and methods: Whole-exome sequencing was carried
out in 15 SC patients and on data from 10 previously published cases.
Hierarchical clustering and consensus non-negative matrix factorization were
carried out for samples classification based on mutational signatures. Results:
In the two series, SC distributed between two clusters (C): Csig4 (characterized
by signature 4) and Csig2-3-13 (signatures 2, 3, and 13). Csig4 exhibited more
frequent MAPK pathway mutations than Csig2-3-13 (pooled series: n = 10/14 versus
2/11, P < 0.05, respectively) and stronger PD-L1 expression (our series: n = 6/9
versus 1/6, P = 0.12). MET alterations were only found in Csig2-3-13 (pooled
series: n = 5/11 versus 0/14, P = 0.009), as well as BRCA1/BRCA2 (n = 3/11 versus
0/15), EGFR (n = 1), and IDH1 (n = 1) mutations. Csig2-3-13 patients had better
overall survival than Csig4 patients (median: >45 versus 7 months, respectively,
P = 0.001). Conclusions: Our study suggests that SC presents at least two
clusters comprising different mutational processes, gene alterations, and PD-L1
expression. New potential treatment possibilities are immune checkpoint
inhibitors in Csig4 and specific targeted agents in Csig2-3-13. These findings
should encourage clinicians to conduct broad molecular and immunological testing
in SC patients beyond MET exon 14 alterations.
PMID- 28419183
TI - Comparison of the Mutational Profiles of Primary Myelofibrosis, Polycythemia
Vera, and Essential Thrombocytosis.
AB - Objectives: To compare the mutational profiles of patients with primary
myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET).
Methods: Next-generation sequencing results of 75 cases of PMF, 33 cases of PV,
and 27 cases of ET were compared. Results: Mutation rates of ASXL1 and SRSF2 were
significantly higher in PMF than in PV or ET. ASXL1 mutations appeared to be more
frequently associated with risk of transformation to acute myeloid leukemia than
JAK2 or TET2 mutations. The most common mutation-cytogenetic combinations in
myeloproliferative neoplasm (MPN) were mutations of JAK2 or ASXL1 with del(20q)
and were more common in patients with PMF and PV than in patients with ET.
Differences were also found between patients with PMF and PV. Conclusions: PMF,
PV, and ET show different mutational profiles, which may be helpful in resolving
the differential diagnosis between MPNs. Due to the relatively small number of
cases and variable testing over time, larger controlled studies are necessary to
confirm the findings.
PMID- 28419184
TI - Mechanisms for the species difference between mouse and pig oocytes in their
sensitivity to glucorticoids.
AB - Although in vitro exposure to physiological concentrations of glucorticoids did
not affect maturation of mouse oocytes, it significantly inhibited nuclear
maturation of pig oocytes. Studies on this species difference in oocyte
sensitivity to glucocorticoids will contribute to our understanding of how
stress/glucocorticoids affect oocytes. We showed that glucorticoid receptors
(NR3C1) were expressed in both oocytes and cumulus cells (CCs) of both pigs and
mice; however, while cortisol inhibition of oocyte maturation was overcome by
NR3C1 inhibitor RU486 in pigs, it could not be relieved by RU486 in mice. The
mRNA level of 11beta-hydroxysteroid dehydrogenase 1 (HSD11B1) was significantly
higher than that of HSD11B2 in pig cumulus-oocyte complexes (COCs), whereas
HSD11B2 was exclusively expressed in mouse COCs. Pig and mouse cumulus-denuded
oocytes (DOs) expressed HSD11B2 predominantly and exclusively, respectively. In
the presence of cortisol, although inhibiting HSD11B2 decreased maturation rates
of COCs in both species, inhibiting HSD11B1 improved maturation of pig COCs while
having no effect on mouse COCs. Cortisol-cortisone interconversion observation
confirmed high HSD11B1 activities in pig oocytes but none in mouse oocytes, a
higher HSD11B2 activity in mouse than in pig oocytes, and a rapid cortisol
cortisone interconversion in pig COCs catalyzed by HSD11B1 from CCs and HSD11B2
from DOs. In conclusion, the species difference in glucocorticoid sensitivity
between pig and mouse oocytes is caused by their different contents/ratios of
HSD11B1 and HSD11B2, which maintain different concentrations of active
glucocorticoids. While cortisol inhibited pig oocytes by interacting with NR3C1,
glucocorticoid suppression of mouse oocytes was apparently not mediated by NR3C1.
PMID- 28419185
TI - A New Automated Technology for Cerebrospinal Fluid Cell Counts: Comparison of
Accuracy and Clinical Impact of GloCyte, Sysmex XN, and Manual Methods.
AB - Objectives: The purpose of the study was to compare the performance of GloCyte
(Advanced Instruments, Norwood, MA), a new semiautomated instrument for
cerebrospinal fluid cell counting, with the manual hemocytometer method and the
automated Sysmex XN (Sysmex, Kobe, Japan) body fluid mode. The clinical impact of
replacing the manual method with either automated method was determined. Methods:
Fifty-seven samples from 38 patients were analyzed by all three methods. Pearson
correlation and Passing-Bablok regression were used to compare methods. Cytospin
smears were reviewed on all samples, and clinical histories were obtained.
Results: There was a strong linear relationship between the manual and automated
methods for WBC counts ( R = 0.988 for GloCyte; R = 0.980 for Sysmex XN).
Positive bias was absent or negligible for WBC counts less than 30/MUL. GloCyte
and manual RBC counts were equivalent. There were no samples for which
replacement of manual WBC counts by automated counts would have changed the
diagnosis. Both automated methods showed improved precision for WBC counts
compared with the manual method. Conclusions: Replacing manual WBC counts by
GloCyte or Sysmex XN WBC counts would improve consistency of results without
compromising diagnostic accuracy.
PMID- 28419186
TI - CD4-Negative Variant of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm
With a Novel PBRM1 Mutation in an 11-Year-Old Girl.
AB - Objectives: We report a rare case of CD4- cutaneous blastic plasmacytoid
dendritic cell neoplasm (BPDCN) with a novel PBRM1 mutation. Methods: An 11-year
old girl presented with an enlarged mass on her left arm and underwent an
incisional biopsy. Results: Histopathologic examination and immunohistochemistry
studies showed a monotonous proliferation of blasts that were CD4-, CD56+, and
CD123+. There was no evidence of leukemic dissemination. Next-generation
sequencing detected PBRM1 and CIC gene abnormalities. We confirmed and validated
a novel PBRM1 mutation by conventional polymerase chain reaction and Sanger
sequencing. Conclusions: CD4- variant of BPDCN may be mistaken for myeloid
sarcoma or extramedullary lymphoblastic leukemia/lymphoma because of their
overlapping morphologic and immunophenotypic features; thus, a careful
clinicopathologic evaluation is essential to reach the correct diagnosis. PBRM1
mutation seems to be a driver event in this case. Our study underscores the
importance of alterations in chromatin remodeling in the pathogenesis of BPDCN.
PMID- 28419187
TI - Kaposi sarcoma in a patient treated with ruxolitinib.
PMID- 28419188
TI - Interactive Book Reading to Accelerate Word Learning by Kindergarten Children
With Specific Language Impairment: Identifying Adequate Progress and Successful
Learning Patterns.
AB - Purpose: The goal of this study was to provide guidance to clinicians on early
benchmarks of successful word learning in an interactive book reading treatment
and to examine how encoding and memory evolution during treatment contribute to
word learning outcomes by kindergarten children with specific language impairment
(SLI). Method: Twenty-seven kindergarten children with SLI participated in a
preliminary clinical trial using interactive book reading to teach 30 new words.
Word learning was assessed at 4 points during treatment through a picture naming
test. Results: The results indicate that the following performance during
treatment was cause for concern, indicating a need to modify the treatment:
naming 0-1 treated words correctly at Naming Test 1; naming 0-2 treated words
correctly at Naming Test 2; naming 0-3 treated words correctly at Naming Test 3.
In addition, the results showed that encoding was the primary limiting factor in
word learning, but rmemory evolution also contributed (albeit to a lesser degree)
to word learning success. Conclusion: Case illustrations demonstrate how a
clinician's understanding of a child's word learning strengths and weaknesses
develop over the course of treatment, substantiating the importance of regular
data collection and clinical decision-making to ensure the best possible outcomes
for each individual child.
PMID- 28419190
TI - Chainy: an universal tool for standardized relative quantification in real-time
PCR.
PMID- 28419189
TI - Propensity scores with misclassified treatment assignment: a likelihood-based
adjustment.
AB - Propensity score methods are widely used in comparative effectiveness research
using claims data. In this context, the inaccuracy of procedural or billing codes
in claims data frequently misclassifies patients into treatment groups, that is,
the treatment assignment ($T$) is often measured with error. In the context of a
validation data where treatment assignment is accurate, we show that
misclassification of treatment assignment can impact three distinct stages of a
propensity score analysis: (i) propensity score estimation; (ii) propensity score
implementation; and (iii) outcome analysis conducted conditional on the estimated
propensity score and its implementation. We examine how the error in $T$ impacts
each stage in the context of three common propensity score implementations:
subclassification, matching, and inverse probability of treatment weighting
(IPTW). Using validation data, we propose a two-step likelihood-based approach
which fully adjusts for treatment misclassification bias under subclassification.
This approach relies on two common measurement error-assumptions; non
differential measurement error and transportability of the measurement error
model. We use simulation studies to assess the performance of the adjustment
under subclassification, and also investigate the method's performance under
matching or IPTW. We apply the methods to Medicare Part A hospital claims data to
estimate the effect of resection versus biopsy on 1-year mortality among
$10?,284$ Medicare beneficiaries diagnosed with brain tumors. The ICD9 billing
codes from Medicare Part A inaccurately reflect surgical treatment, but SEER
Medicare validation data are available with more accurate information.
PMID- 28419191
TI - PPARdelta promotes tumor progression via activation of Glut1 and SLC1-A5
transcription.
AB - Malignant cancer cell uncontrolled growth depends on the persistent nutrient
availability such as glucose and amino acids, which is required for cancer cell
energetic and biosynthetic pathways. As a nuclear hormone receptor, peroxisome
proliferator-activated receptor delta (PPARdelta) plays a critical role in
inflammation and cancer, however, it is still unclear the regulatory mechanism of
PPARdelta on cancer cell metabolism. Here, we found that PPARdelta directly
regulated neutral amino acid transporter SLC1-A5 (solute carrier family 1 member
5) and glucose transporter-1 (Glut1) gene transcription, leading to uptake of
glucose and amino acid, activation of mTOR signaling, and tumor progression. In
contrast, silence of PPARdelta or its antagonist inhibited this event. More
importantly, PPARdelta promoted cancer cell metabolic reprogramming resulting in
chemoresistance, which was alleviated by PPARdelta antagonist. These findings
revealed a novel mechanism of PPARdelta-mediated tumor progression, which
provided a potential strategy for cancer treatment.
PMID- 28419192
TI - Efficacy and safety of a novel acetylcholinesterase inhibitor
octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II
multicenter randomised controlled trial.
AB - Background: inhibition of acetylcholinesterase (AChE) has been a effective
treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE
inhibitor, is a potential treatment for AD. Method: we conducted a multicenter,
randomised, double blind, placebo-controlled, parallel-group Phase II clinical
trial to investigate the effects of octohydroaminoacridine in patients with mild
to-moderate AD. Patients were randomised to receive placebo thrice daily,
octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle
dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose
group were titrated over 2-4 weeks. Changes from baseline to Week 16 were
assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's
Interview-Based Impression of Change Plus (CIBIC+), activities of daily living
(ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end
point of the study. A two-way analysis of covariance and least squares mean t
test were used. Results: at Week 16, the changes from baseline in ADAS-cog were
1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups,
respectively. Patients in the high-dose group had better performance in CIBIC+
and ADL scores at the end of the study. There was no significant difference in
the change in NPI score among the groups. The effects of octohydroaminoacridine
were dose dependent, and were effective within 16 weeks of treatment. No evidence
was found for more adverse events that occurred in different drug groups than
placebo group. Conclusions: octohydroaminoacridine significantly improved
cognitive function and behaviour in patients with mild-to-moderate AD and this
effect was dose dependent.
PMID- 28419193
TI - A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or
locally advanced transitional cell carcinoma of the urothelium (SECAVIN).
AB - Background: Despite the advent of immunotherapy in urothelial cancer, there is
still a need to find effective cytotoxic agents beyond first and second lines.
Vinflunine is the only treatment approved in this setting by the European
Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is
a taxane with activity in docetaxel-refractory cancers. A randomized study was
conducted to compare its efficacy versus vinflunine. Patients and methods: This
is a multicenter, randomized, open-label, phase II/III study, following a Simon's
optimal method with stopping rules based on an interim futility analysis and a
formal efficacy analysis at the end of the phase II. ECOG Performance Status,
anaemia and liver metastases were stratification factors. Primary objectives were
overall response rate for the phase II and overall survival for the phase III.
Results: Seventy patients were included in the phase II across 19 institutions in
Europe. Baseline characteristics were well balanced between the two arms. Three
patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and
six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression
free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P =
0.039). The study did not proceed to phase III since the futility analysis showed
a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found
favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related
adverse events were seen in 41% patients with no difference between the two arms.
Conclusion: This phase II/III second line bladder study comparing cabazitaxel
with vinflunine was closed when the phase II showed a lack of efficacy of the
cabazitaxel arm. Vinflunine results were consistent with those known previously.
Trial number: NCT01830231.
PMID- 28419194
TI - DMINDA 2.0: integrated and systematic views of regulatory DNA motif
identification and analyses.
AB - Motivation: Motif identification and analyses are important and have been long
standing computational problems in bioinformatics. Substantial efforts have been
made in this field during the past several decades. However, the lack of
intuitive and integrative web servers impedes the progress of making effective
use of emerging algorithms and tools. Results: Here we present an integrated web
server, DMINDA 2.0, which contains: (i) five motif prediction and analyses
algorithms, including a phylogenetic footprinting framework; (ii) 2125 species
with complete genomes to support the above five functions, covering animals,
plants and bacteria and (iii) bacterial regulon prediction and visualization.
Availability and Implementation: DMINDA 2.0 is freely available at
http://bmbl.sdstate.edu/DMINDA2. Contact: qin.ma@sdstate.edu. Supplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 28419196
TI - The Need for Outcome Studies Prior to Large-Scale Implementation of Screening for
Anal Cancer.
PMID- 28419195
TI - Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of
metastatic colorectal cancer patients.
AB - Background: RAS assessment is mandatory for therapy decision in metastatic
colorectal cancer (mCRC) patients. This determination is based on tumor tissue,
however, genotyping of circulating tumor (ct)DNA offers clear advantages as a
minimally invasive method that represents tumor heterogeneity. Our study aims to
evaluate the use of ctDNA as an alternative for determining baseline RAS status
and subsequent monitoring of RAS mutations during therapy as a component of
routine clinical practice. Patients and methods: RAS mutational status in plasma
was evaluated in mCRC patients by OncoBEAMTM RAS CRC assay. Concordance of
results in plasma and tissue was retrospectively evaluated. RAS mutations were
also prospectively monitored in longitudinal plasma samples from selected
patients. Results: Analysis of RAS in tissue and plasma samples from 115 mCRC
patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were
mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico
pathological features showed that the site of metastasis (i.e. peritoneal, lung),
the histology of the tumor (i.e. mucinous) and administration of treatment
previous to blood collection negatively impacted the detection of RAS in ctDNA.
In patients with baseline mutant RAS tumors treated with
chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response
to treatment, being an early predictor of response. In patients RAS wt,
longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect
emergence of RAS mutations during anti-EGFR treatment. Conclusion: The high
overall agreement in RAS mutational assessment between plasma and tissue supports
blood-based testing with OncoBEAMTM as a viable alternative for genotyping RAS of
mCRC patients in routine clinical practice. Our study describes practical clinico
pathological specifications to optimize RAS ctDNA determination. Moreover,
OncoBEAMTM is useful to monitor RAS in patients undergoing systemic therapy to
detect resistance and evaluate the efficacy of particular treatments.
PMID- 28419197
TI - Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly
corrects metabolism and restores function in the diabetic heart following
hypoxia/reoxygenation.
AB - Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can
impair metabolic flexibility and function. Increased sarcolemmal fatty acid
translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium,
feeding increased fatty acid oxidation and elevated lipid deposition. Unlike
other metabolic modulators that target mitochondrial fatty acid oxidation, we
proposed that pharmacologically inhibiting fatty acid uptake, as the primary step
in the pathway, would provide an alternative mechanism to rebalance metabolism
and prevent lipid accumulation following hypoxic stress. Methods and results:
Hearts from type 2 diabetic and control male Wistar rats were perfused in
normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N
succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into
diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial
triglyceride concentration by 48% compared with untreated diabetic hearts,
restoring fatty acid metabolism to control levels following hypoxia
reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic
hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and
decreased lactate efflux rate by 56% compared with untreated diabetic hearts
during reoxygenation. In addition, SSO treatment of diabetic hearts increased
intermediates within the second span of the Krebs cycle, namely fumarate,
oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts
following decreased oxygen availability was prevented by SSO-infusion prior to
the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure
product by 60% during hypoxia and by 32% following reoxygenation, restoring
function to control levels. Conclusions: Diabetic hearts have limited metabolic
flexibility and cardiac dysfunction when stressed, which can be rapidly rectified
by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel
therapeutic approach not only reduces fat oxidation but also lipotoxicity, by
targeting the primary step in the fatty acid metabolism pathway.
PMID- 28419199
TI - Should We Revisit the Nephrotoxic Potential of Piperacillin-Tazobactam as Well?
PMID- 28419198
TI - Increased Syphilis Testing of Men Who Have Sex With Men: Greater Detection of
Asymptomatic Early Syphilis and Relative Reduction in Secondary Syphilis.
AB - Background: Syphilis rates have increased markedly among men who have sex with
men (MSM) internationally. We examined trends in syphilis testing and detection
of early syphilis among MSM in Australia. Methods: Serial cross-sectional
analyses on syphilis testing and diagnoses among MSM attending a national
sentinel network of 46 clinics in Australia between 2007 and 2014. Results:
359313 clinic visits were included. The proportion of MSM serologically tested
for syphilis annually increased in HIV-negative (48% to 91%; Ptrend < .0001) and
HIV-positive MSM (42% to 77%; Ptrend < .0001). The mean number of tests per man
per year increased from 1.3 to 1.6 in HIV-negative MSM (Ptrend < .0001) and from
1.6 to 2.3 in HIV-positive MSM (Ptrend < .0001). 2799 and 1032 syphilis cases
were detected in HIV-negative and HIV-positive MSM, respectively. Among HIV
negative MSM, the proportion of infections that were early latent increased from
27% to 44% (Ptrend < .0001), while the proportion that were secondary decreased
from 24% to 19% (Ptrend = .030). Among HIV-positive MSM, early latent infections
increased from 23% to 45% (Ptrend < .0001), while secondary infections decreased
from 45% to 26% (Ptrend = .0003). Among HIV-positive MSM, decreasing secondary
syphilis correlated with increasing testing coverage (r = -0.87; P = .005) or
frequency (r = -0.93; P = .001). Conclusions: Increases in syphilis screening
were associated with increased detection of asymptomatic infectious syphilis and
relative falls in secondary syphilis for both HIV-positive and HIV-negative MSM
nationally, suggesting interruption of syphilis progression.
PMID- 28419200
TI - Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human
Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term
Outcomes of a Randomized Trial.
AB - Background: We previously demonstrated the noninferiority of switching to
efavirenz (EFV) versus remaining on ritonavir-boosted lopinavir (LPV/r) for
virologic control in children infected with human immunodeficiency virus (HIV)
and exposed to nevirapine (NVP) for prevention of mother-to-child transmission.
Here we assess outcomes up to 4 years post-randomization. Methods: From 2010
2013, 298 NVP-exposed HIV-infected children >=3 years of age were randomized to
switch to EFV or remain on LPV/r in Johannesburg, South Africa
(Clinicaltrials.gov NCT01146873). After trial completion, participants were
invited to enroll into observational follow-up. We compared HIV RNA levels, CD4
counts and percentages, lipids, and growth across groups through four years post
randomization. Results: HIV RNA levels 51-1000 copies/mL were less frequently
observed in the EFV group than the LPV/r group (odds ratio [OR] 0.67, 95%
confidence interval [CI]: 0.51-0.88, P = .004), as was HIV RNA >1000 copies/mL
(OR 0.52 95% CI: 0.28-0.98, P = .04). The probability of confirmed HIV RNA >1000
copies/mL by 48 months was 0.07 and 0.12 in the EFV and LPV/r groups,
respectively (P = .21). Children randomized to EFV had a reduced risk of elevated
total cholesterol (OR 0.45 95% CI: 0.27-0.75, P = .002) and a reduced risk of
abnormal triglycerides (OR 0.42, 95% CI 0.29-0.62, P < .001). Conclusions: Our
results indicate that the benefits of switching virologically suppressed NVP
exposed HIV-infected children >=3 years of age from LPV/r to EFV are sustained
long-term. This approach has several advantages, including improved palatability,
reduced metabolic toxicity, simplified cotreatment for tuberculosis, and
preservation of second line options. Clinical Trials Registration: NCT01146873.
PMID- 28419201
TI - Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How
do Lapses in Monkey Performance Affect Cross-Species Correspondences?
AB - The cross-species correspondences and differences in how attention modulates
brain responses in humans and animal models are poorly understood. We trained 2
monkeys to perform an audio-visual selective attention task during functional
magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one
modality while ignoring those in the other. Monkey fMRI identified regions
strongly modulated by auditory or visual attention. Surprisingly, auditory
attention-related modulations were much more restricted in monkeys than humans
performing the same tasks during fMRI. Further analyses ruled out trivial
explanations, suggesting that labile selective-attention performance was
associated with inhomogeneous modulations in wide cortical regions in the
monkeys. The findings provide initial insights into how audio-visual selective
attention modulates the primate brain, identify sources for "lost" attention
effects in monkeys, and carry implications for modeling the neurobiology of human
cognition with nonhuman animals.
PMID- 28419202
TI - Genomic Characterization of USA300 Methicillin-Resistant Staphylococcus aureus
(MRSA) to Evaluate Intraclass Transmission and Recurrence of Skin and Soft Tissue
Infection (SSTI) Among High-Risk Military Trainees.
AB - Background: Military trainees are at increased risk for methicillin-resistant
Staphylococcus aureus (MRSA) skin and soft tissue infection (SSTI). Whole genome
sequencing (WGS) can refine our understanding of MRSA transmission and
microevolution in congregate settings. Methods: We conducted a prospective case
control study of SSTI among US Army infantry trainees at Fort Benning, Georgia,
from July 2012 to December 2014. We identified clusters of USA300 MRSA SSTI
within select training classes and performed WGS on clinical isolates. We then
linked genomic, phylogenetic, epidemiologic, and clinical data in order to
evaluate intra- and interclass disease transmission. Furthermore, among cases of
recurrent MRSA SSTI, we evaluated the intrahost relatedness of infecting strains.
Results: Nine training classes with >=5 cases of USA300 MRSA SSTI were selected.
Eighty USA300 MRSA clinical isolates from 74 trainees, 6 (8.1%) of whom had
recurrent infection, were subjected to WGS. We identified 2719 single nucleotide
variants (SNVs). The overall median (range) SNV difference between isolates was
173 (1-339). Intraclass median SNV differences ranged from 23 to 245. Two
phylogenetic clusters were suggestive of interclass MRSA transmission. One of
these clusters stemmed from 2 classes that were separated by a 13-month period
but housed in the same barracks. Among trainees with recurrent MRSA SSTI, the
intrahost median SNV difference was 7.5 (1-48). Conclusions: Application of WGS
revealed intra- and interclass transmission of MRSA among military trainees. An
interclass cluster between 2 noncontemporaneous classes suggests a long-term
reservoir for MRSA in this setting.
PMID- 28419203
TI - Selective Cutoff Reporting in Studies of Diagnostic Test Accuracy: A Comparison
of Conventional and Individual-Patient-Data Meta-Analyses of the Patient Health
Questionnaire-9 Depression Screening Tool.
AB - In studies of diagnostic test accuracy, authors sometimes report results only for
a range of cutoff points around data-driven "optimal" cutoffs. We assessed
selective cutoff reporting in studies of the diagnostic accuracy of the Patient
Health Questionnaire-9 (PHQ-9) depression screening tool. We compared
conventional meta-analysis of published results only with individual-patient-data
meta-analysis of results derived from all cutoff points, using data from 13 of 16
studies published during 2004-2009 that were included in a published conventional
meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been
published by 11 of the studies. For all other relevant cutoffs, 3-6 studies
published accuracy results. For all cutoffs examined, specificity estimates in
conventional and individual-patient-data meta-analyses were within 1% of each
other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%
15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the
standard cutoff, authors tended to report results for lower cutoffs that yielded
optimal results. When the PHQ-9 was highly sensitive, authors more often reported
results for higher cutoffs. Consequently, in the conventional meta-analysis,
sensitivity increased as cutoff severity increased across part of the cutoff
range-an impossibility if all data are analyzed. In sum, selective reporting by
primary study authors of only results from cutoffs that perform well in their
study can bias accuracy estimates in meta-analyses of published results.
PMID- 28419205
TI - Comparison of clinical features and survival between thymic carcinoma and thymic
carcinoid patients.
AB - OBJECTIVES: Thymic carcinoma (TC) and thymic carcinoid (TCD) are aggressive
thymic epithelial neoplasms with a poor prognosis. Due to rarity, little is known
about their comparative clinical characteristics, treatment outcomes and patterns
of relapse. METHODS: A retrospective cohort study was performed on 287 patients
with TC and 56 patients with TCD who were treated at the Shanghai Chest Hospital
between February 2003 and April 2014. Patient demographics, tumour stage,
treatment, pathologic findings and postoperative outcomes were compared between
the two tumour types using both multivariable Cox regression analysis and
propensity-matched analysis. RESULTS: Compared to patients with TC, significantly
more patients with TCD were male, had larger tumours, and displayed a greater
proportion of lymph node metastases. However, overall survival was similar (60.7%
5-year survival for TC, 80.7% for TCD, P = 0.159), as was disease-free survival
(41.1% 5-year survival for TC, 37.6% for TCD, P = 0.696) and patterns of
relapse. Multiple Cox regression analysis identified younger patients [hazard
ratio (HR) 1.018; 95% confidence interval (CI) 1.000-1.035; P = 0.047], more
completeness of resection (HR 1.424; 95% CI 1.105-1.836; P = 0.006), adjuvant
radiotherapy (HR 0.455; 95% CI 0.276-0.751; P = 0.002), and no adjuvant
chemotherapy (HR 1.799; 95% CI 1.017-3.183; P = 0.044) as independent factors
predicting better overall survival. Completeness of resection (HR 1.258; 95% CI
1.022-1.548; P = 0.031) and TNM stage (HR 1.479; 95% CI 1.107-1.977; P = 0.008)
were independent predictors of disease-free survival. Propensity matching
produced 46 patients in each group and no significant difference on overall
survival or disease-free survival was found. CONCLUSIONS: Patients with TCD have
discrete features but share a similar clinical course to those with TC. The
importance of complete resection in both of these thymic malignancies is
emphasized. Further investigation at multiple centers with the longer follow-up
data is required to substantiate our conclusion.
PMID- 28419204
TI - Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes
Multiple Individual Wild and Vaccine-Derived Polioviruses.
AB - Background: A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is
the rational option for completely eradicating poliovirus transmission. The
neutralizing capacity of Sabin-IPV immune serum to different strains of
poliovirus is a key indicator of the clinical protective efficacy of this
vaccine. Methods: Sera collected from 500 infants enrolled in a randomized,
blinded, positive control, phase 2 clinical trial were randomly divided into 5
groups: Groups A, B, and C received high, medium, and low doses, respectively, of
Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk
strain-based IPV, respectively, all on the same schedule. Immune sera were
collected after the third dose of primary immunization, and tested in cross
neutralization assays against 19 poliovirus strains of all 3 types. Results: All
immune sera from all 5 groups interacted with the 19 poliovirus strains with
various titers and in a dose-dependent manner. One type 2 immunodeficiency
associated vaccine-derived poliovirus strain was not recognized by these immune
sera. Conclusions: Sabin-IPV vaccine can induce protective antibodies against
currently circulating and reference wild poliovirus strains and most vaccine
derived poliovirus strains, with rare exceptions. Clinical Trials Registration:
NCT01056705.
PMID- 28419206
TI - Short-term preoperative exercise therapy does not improve long-term outcome after
lung cancer surgery: a randomized controlled study.
AB - OBJECTIVES: Poor aerobic fitness is a potential modifiable risk factor for long
term survival and quality of life in patients with lung cancer. This randomized
trial evaluates the impact of adding rehabilitation (Rehab) with high-intensity
interval training (HIIT) before lung cancer surgery to enhance cardiorespiratory
fitness and improve long-term postoperative outcome. METHODS: Patients with
operable lung cancer were randomly assigned to usual care (UC, n = 77) or to
intervention group (Rehab, n = 74) that entailed HIIT that was implemented only
preoperatively. Cardiopulmonary exercise testing (CPET) and pulmonary functional
tests (PFTs) including forced vital capacity (FVC), forced expiratory volume (FEV
1 ) and carbon monoxide transfer factor (KCO) were performed before and 1 year
after surgery. RESULTS: During the preoperative waiting time (median 25 days),
Rehab patients participated to a median of 8 HIIT sessions (interquartile [IQ] 25
75%, 7-10). At 1 year follow-up, 91% UC patients and 93% Rehab patients were
still alive ( P = 0.506). Pulmonary functional changes were non-significant and
comparable in both groups (FEV 1 mean -7.5%, 95% CI, -3.6 to -12.9 and in KCO
mean 5.8% 95% CI 0.8-11.8) Compared with preoperative CPET results, both groups
demonstrated similar reduction in peak oxygen uptake (mean -12.2% 95% CI -4.8 to
18.2) and in peak work rate (mean -11.1% 95% CI -4.2 to -17.4). CONCLUSIONS:
Short-term preoperative rehabilitation with HIIT does not improve pulmonary
function and aerobic capacity measured at 1 year after lung cancer resection.
TRIAL REGISTRY: ClinicalTrials.gov; No. NCT01258478; www.clinicaltrials.gov .
PMID- 28419207
TI - CKII-SIRT1-SM22alpha loop evokes a self-limited inflammatory response in vascular
smooth muscle cells.
AB - Aims: Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-kappaB) activity in
response to the inflammatory cytokine tumour necrosis factor alpha (TNF-alpha).
Smooth muscle (SM) 22alpha is a phosphorylation-regulated suppressor of IKK
IkappaBalpha-NF-kappaB signalling cascades in vascular smooth muscle cells
(VSMCs). Sm22alpha knockout results in increased expression of pro-inflammatory
genes in the aortas which are controlled by NF-kappaB. This study aimed to
investigate the relationship between SM22alpha and SIRT1 in the control of
vascular inflammation. Methods and results: The ligation injury model of Sirt1
Tg/Sm22alpha-/- mice displayed an increased level of the inflammatory molecules
in the carotid arteries compared with Sirt1-Tg mice, accompanied with aggravating
neointimal hyperplasia. In the in vitro study, on the one hand, we showed that
TNF-alpha induced the epigenetic silencing of SM22alpha transcription via EZH2
mediated H3K27 methylation in the SM22alpha promoter region, contributing to
inflammatory response. On the other hand, TNF-alpha simultaneously induced SIRT1
phosphorylation via CKII and thereby protected against inflammation.
Phosphorylated SIRT1 interacted with and deacetylated EZH2 and, subsequently,
promoted SM22alpha transcription by inhibiting EZH2 activity. Increased SM22alpha
in turn facilitated the phosphorylation and activation of SIRT1 via recruitment
of CKII to SIRT1, which amplified the anti-inflammatory effect of SIRT1.
Conclusion: Our findings demonstrate that, in response to TNF-alpha stimulation,
CKII-SIRT1-SM22alpha acts in a loop to reinforce the expression of SM22alpha,
which limits the inflammatory response in VSMCs in vivo and in vitro. The anti
inflammatory effect of SIRT1 may be dependent on SM22alpha to some extent. Our
data point to targeted activation of SIRT1 in VSMCs as a promising therapeutic
avenue in preventing cardiovascular diseases.
PMID- 28419208
TI - Interhemispheric Synchrony of Spontaneous Cortical States at the Cortical Column
Level.
AB - In cat early visual cortex, neural activity patterns resembling evoked
orientation maps emerge spontaneously under anesthesia. To test if such patterns
are synchronized between hemispheres, we performed bilateral imaging in
anesthetized cats using a new improved voltage-sensitive dye. We observed map
like activity patterns spanning early visual cortex in both hemispheres
simultaneously. Patterns virtually identical to maps associated with the cardinal
and oblique orientations emerged as leading principal components of the
spontaneous fluctuations, and the strength of transient orientation states was
correlated with their duration, providing evidence that these maps are
transiently attracting states. A neural mass model we developed reproduced the
dynamics of both smooth and abrupt orientation state transitions observed
experimentally. The model suggests that map-like activity arises from slow
modulations in spontaneous firing in conjunction with interplay between
excitation and inhibition. Our results highlight the efficiency and functional
precision of interhemispheric connectivity.
PMID- 28419209
TI - Estrogen Deficiency Exacerbates Type 1 Diabetes-Induced Bone TNF-alpha Expression
and Osteoporosis in Female Mice.
AB - Estrogen deficiency after menopause is associated with rapid bone loss,
osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized
by hypoinsulinemia and hyperglycemia, is also associated with bone loss and
increased fracture risk. With better treatment options, T1D patients are living
longer; therefore, the number of patients having both T1D and estrogen deficiency
is increasing. Little is known about the mechanistic impact of T1D in conjunction
with estrogen deficiency on bone physiology and density. To investigate this, 11
week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose
streptozotocin injection. Microcomputed tomographic analysis indicated a marked
reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that
was far greater than the reductions (~50%) in BVF in either the OVX and T1D
groups. Osteoblast markers, number, and activity were significantly decreased in
T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly,
marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone
expression analyses revealed that tumor necrosis factor (TNF)-alpha levels were
highest in T1D-OVX mice and correlated with bone loss, and osteoblast and
osteocyte death. In vitro studies indicate that estrogen deficiency and high
glucose enhance TNF-alpha expression in response to inflammatory signals. Taken
together, T1D combined with estrogen deficiency has a major effect on bone
inflammation, which contributes to suppressed bone formation and osteoporosis.
Understanding the mechanisms/effects of estrogen deficiency in the presence of
T1D on bone health is essential for fracture prevention in this patient
population.
PMID- 28419210
TI - Dasatinib Use and Risk of Cytomegalovirus Reactivation After Allogeneic
Hematopoietic-Cell Transplantation.
AB - Viral infections have been reported with dasatinib use, but its cytomegalovirus
risk after hematopoietic-cell transplantation (HCT) is not known. We found that
post-HCT dasatinib use increased the risk of cytomegalovirus reactivation
(adjusted hazard ratio, 7.65; 95% confidence interval, 1.84-31.7), controlling
for acute graft-versus-host disease, in 109 patients with Philadelphia-chromosome
positive malignancies.
PMID- 28419212
TI - Pleurectomy-decortication in malignant pleural mesothelioma: are different
surgical techniques associated with different outcomes? Results from a
multicentre study.
AB - OBJECTIVES: The potential benefit of surgery for malignant pleural mesothelioma
(MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the
literature. The aim of this study was to evaluate the outcome after multimodality
treatment of MPM involving different types of P/D and to analyse the prognostic
factors. METHODS: We reviewed 314 patients affected by MPM who were operated on
in 11 Italian centres from 1 January 2007 to 11 October 2014. RESULTS: The
characteristics of the population were male/female ratio: 3.7/1, and median age
at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of
patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III
disease was found following a pathological analysis in 62.3% of cases. A total of
162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D
and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was
delivered in 39.2% of patients. Median overall survival time after surgery was
23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox)
analysis, pathological Stage III-IV [ P = 0.004, hazard ratio (HR):1.34; 95% CI:
1.09-1.64], EP/D and P/D ( P = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR
for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P = 0.01, HR: 1.52; 95%
CI: 1.09-2.12) and pathological status T4 ( P = 0.0003, HR: 1.38; 95% CI: 1.14
1.66) were found to be independent significant predictors of overall survival.
CONCLUSIONS: Whether the P/D is extended or not, it shows similarly good outcomes
in terms of early results and survival rate. In contrast, a partial pleurectomy,
which leaves gross tumour behind, has no impact on survival.
PMID- 28419211
TI - The Inhibitory G Protein alpha-Subunit, Galphaz, Promotes Type 1 Diabetes-Like
Pathophysiology in NOD Mice.
AB - The alpha-subunit of the heterotrimeric Gz protein, Galphaz, promotes beta-cell
death and inhibits beta-cell replication when pancreatic islets are challenged by
stressors. Thus, we hypothesized that loss of Galphaz protein would preserve
functional beta-cell mass in the nonobese diabetic (NOD) model, protecting from
overt diabetes. We saw that protection from diabetes was robust and durable up to
35 weeks of age in Galphaz knockout mice. By 17 weeks of age, Galphaz-null NOD
mice had significantly higher diabetes-free survival than wild-type littermates.
Islets from these mice had reduced markers of proinflammatory immune cell
infiltration on both the histological and transcript levels and secreted more
insulin in response to glucose. Further analyses of pancreas sections revealed
significantly fewer terminal deoxynucleotidyltransferase-mediated dUTP nick end
labeling (TUNEL)-positive beta-cells in Galphaz-null islets despite similar
immune infiltration in control mice. Islets from Galphaz-null mice also exhibited
a higher percentage of Ki-67-positive beta-cells, a measure of proliferation,
even in the presence of immune infiltration. Finally, beta-cell-specific Galphaz
null mice phenocopy whole-body Galphaz-null mice in their protection from
developing hyperglycemia after streptozotocin administration, supporting a beta
cell-centric role for Galphaz in diabetes pathophysiology. We propose that
Galphaz plays a key role in beta-cell signaling that becomes dysfunctional in the
type 1 diabetes setting, accelerating the death of beta-cells, which promotes
further accumulation of immune cells in the pancreatic islets, and inhibiting a
restorative proliferative response.
PMID- 28419214
TI - The Evidence That Increased Syphilis Testing Controls Syphilis Is Compelling:
What Is Needed to Act?
PMID- 28419213
TI - Risk Factors for Congenital Cytomegalovirus Infection Following Primary and
Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using
Polymerase Chain Reaction in Saliva.
AB - Background: The design of diagnostic and preventive strategies have been
prevented by gaps in knowledge of the epidemiology of congenital cytomegalovirus
(cCMV) with the type of maternal infection as well as the lack of large-scale
neonatal screening tools. Methods: In sum, 11715 consecutive newborns were
screened for cCMV by polymerase chain reaction (PCR) in saliva. Prevalence, type
of maternal infection, sociodemographic, obstetrical, and serological data were
analyzed. Results: Positive predictive value of CMV PCR in saliva was 59%; false
positive results were associated with lower viral loads (P < .001). Maternal
seroprevalence was 61%, birth prevalence was 0.37%, resulting from primary and
nonprimary infections in 52% and 47.7% of cases, respectively. The risk to
deliver an infected baby after primary infection was increased in younger (OD =
7.9), parous (OD = 4.1) women born in high resources countries (OD = 5.2) and
from higher income groups (P = .019). The only 2 risk factors to deliver an
infected baby after nonprimary infection were to be young (OD = 4.6) and
unemployed (OD = 5.8). The risk to deliver an infected baby was 4-fold higher in
women seronegative before their pregnancy (P = .021). Conclusions: A positive CMV
PCR in newborns' saliva should always be confirmed in a repeat-sample.
Sociodemographic characteristics of women giving birth to an infected baby after
primary and nonprimary infection are different. Seronegative, parous women
represent the highest risk population for cCMV in countries with low to
intermediate seroprevalence. Urgent action is needed to stop the cCMV's epidemic,
particularly in this population easily identifiable by maternal serology and
amenable to prevention messages. Clinical Trials Registration: NCT01923636.
PMID- 28419215
TI - Reply to Allan-Blitz and Klausner.
PMID- 28419217
TI - Shock efficacy of single and dual coil electrodes-new insights from the NORDIC
ICD Trial.
AB - Aims: Dual coil (DC) electrodes are preferred to single coil (SC) electrodes
because of an assumed higher shock efficacy. However, DC-electrodes may be
associated with an increased difficulty and risk of lead extraction. We aimed to
compare SC- and DC-electrodes with respect to the first shock efficacy (FSE)
after implantable cardioverter defibrillator (ICD) implantation. Methods and
results: One thousand and seventy-seven patients of the NORDIC ICD trial were
randomly assigned to first time ICD implantation with or without defibrillation
(DF) testing. The electrode configuration was determined before randomization.
One thousand and sixty-seven patients eventually received an ICD, 516 (48.4%)
with a SC- and 551 (51.6%) with a DC-electrode. DC-electrodes were preferentially
selected in older patients, renal failure, atrial fibrillation, dual chamber,
Cardiac Resynchronization Therapy (CRT) devices, angiotensin-converting-enzyme
(ACE) inhibitors/angiotensin (AT) receptor blockers and without Sotalol. However,
the preference of the investigational site was dominant over clinical parameters.
The DF energy at the final electrode position was higher in SC-electrodes
(adjusted difference +1.15 J; P = 0.005; only patients tested). Less patients
with DC-electrodes required intra-operative system reconfiguration (adjusted
difference -3.9; P = 0.046; only patients tested). Using mixed logistic
regression, the FSE was 92.6% in SC- and 97.8% in DC-electrodes (adjusted odds
ratio 4.3 (95% confidence interval [1.9, 9.8]; P < 0.001)). Conclusion: Dual coil
electrode selection mainly depends on the preference of the investigational site
and seems to be preferred in older patients, renal failure, atrial fibrillation,
dual chamber, and CRT devices. Patients with DC-electrodes required less
intraoperative system reconfigurations. Dual coil-electrodes provided a
substantially higher FSE during follow-up. Mortality rates were not significantly
different in patients with DC- and SC-electrodes.
PMID- 28419218
TI - Radiotherapy in a leadless pacemaker.
PMID- 28419216
TI - LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent
mechanism.
AB - Aims: Ageing is associated with impairment of endothelial nitric oxide synthase
(eNOS) and progressive reduction in endothelial function. A genetic study on long
living individuals-who are characterized by delays in ageing and in the onset of
cardiovascular disease-previously revealed I229V (rs2070325) in
bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4)
as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO
production and vasorelaxation through a protein kinase R-like endoplasmic
reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further
characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement
of vascular function. Methods and results: LAV-BPIFB4 upregulated eNOS function
via mobilization of Ca2+ and activation of protein kinase C alpha (PKCalpha).
Indeed, the overexpression of LAV-BPIFB4 in human endothelial cells enhanced ATP
induced Ca2+ mobilization and the translocation of PKCalpha to the plasma
membrane. Coherently, pharmacological inhibition of PKCalpha blunted the positive
effect of LAV-BPIFB4 on eNOS and endothelial function. In addition, although LAV
BPIFB4 lost the ability to activate PKCalpha and eNOS in ex vivo vessels studied
in an external Ca2+-free medium and in vessels from eNOS-/- mice, it still
potentiated endothelial activity, recruiting an alternative mechanism dependent
upon endothelium-derived hyperpolarizing factor (EDHF). Conclusions: We have
identified novel molecular determinants of the beneficial effects of LAV-BPIFB4
on endothelial function, showing the roles of Ca2+ mobilization and PKCalpha in
eNOS activation and of EDHF when eNOS is inhibited. These results highlight the
role LAV-BPIFB4 can have in restoring signals that are lost during ageing.
PMID- 28419219
TI - DNA remodelling by Strict Partial Endoreplication in orchids, an original process
in the plant kingdom.
AB - DNA remodelling during endoreplication appears to be a strong developmental
characteristic in orchids. In this study, we analysed DNA content and nuclei in
41 species of orchids to further map the genome evolution in this plant family.
We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied
corresponds to strict partial endoreplication. Such process is developmentally
regulated in each wild species studied. Cytometry data analyses allowed us to
propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a
fixed proportion, the euploid genome 2C, plus 2 to 32 additional copies of a
complementary part of the genome. The fixed proportion ranged from 89% of the
genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all
148 orchids reported. Insterspecific hybridisation did not suppress this
phenomenon. Interestingly, this process was not observed in mass-produced
epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent
with high transcription activity in endoreplicated nuclei. Our analyses suggest
species-specific chromatin rearrangement. Towards understanding endoreplication,
V. planifolia constitutes a tractable system for isolating the genomic sequences
that confer an advantage via endoreplication from those that apparently suffice
at diploid level.
PMID- 28419221
TI - Should all individuals with a non-diagnostic electrocardiogram undergo ajmaline
challenge to unmask the concealed arrhythmic overlap syndromes?
PMID- 28419220
TI - Genome sequence and physiological analysis of Yamadazyma laniorum f.a. sp. nov.
and a reevaluation of the apocryphal xylose fermentation of its sister species,
Candida tenuis.
AB - Xylose fermentation is a rare trait that is immensely important to the cellulosic
biofuel industry, and Candida tenuis is one of the few yeasts that has been
reported with this trait. Here we report the isolation of two strains
representing a candidate sister species to C. tenuis. Integrated analysis of
genome sequence and physiology suggested the genetic basis of a number of traits,
including variation between the novel species and C. tenuis in lactose metabolism
due to the loss of genes encoding lactose permease and beta-galactosidase in the
former. Surprisingly, physiological characterization revealed that neither the
type strain of C. tenuis nor this novel species fermented xylose in traditional
assays. We reexamined three xylose-fermenting strains previously identified as C.
tenuis and found that these strains belong to the genus Scheffersomyces and are
not C. tenuis. We propose Yamadazyma laniorum f.a. sp. nov. to accommodate our
new strains and designate its type strain as yHMH7 (=CBS 14780 = NRRL Y-63967T).
Furthermore, we propose the transfer of Candida tenuis to the genus Yamadazyma as
Yamadazyma tenuis comb. nov. This approach provides a roadmap for how integrated
genome sequence and physiological analysis can yield insight into the mechanisms
that generate yeast biodiversity.
PMID- 28419222
TI - Reply to Manian.
PMID- 28419223
TI - Removal of batch effects using distribution-matching residual networks.
AB - Motivation: Sources of variability in experimentally derived data include
measurement error in addition to the physical phenomena of interest. This
measurement error is a combination of systematic components, originating from the
measuring instrument and random measurement errors. Several novel biological
technologies, such as mass cytometry and single-cell RNA-seq (scRNA-seq), are
plagued with systematic errors that may severely affect statistical analysis if
the data are not properly calibrated. Results: We propose a novel deep learning
approach for removing systematic batch effects. Our method is based on a residual
neural network, trained to minimize the Maximum Mean Discrepancy between the
multivariate distributions of two replicates, measured in different batches. We
apply our method to mass cytometry and scRNA-seq datasets, and demonstrate that
it effectively attenuates batch effects. Availability and Implementation: our
codes and data are publicly available at
https://github.com/ushaham/BatchEffectRemoval.git. Contact:
yuval.kluger@yale.edu. Supplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 28419224
TI - Avoiding oesophageal injury during cardiac ablation: insights gained from
mediastinal anatomy.
AB - Aims: This study investigates the lateral displacement of the oesophagus at the
level of the left atrium (LA) in 11 cadavers. Methods and results: The study was
conducted using human cadavers. An endotracheal stylet probe was inserted into
the eosphagus. The pericardium overlying the posterior LA was fixed in place. The
lateral movement of the oesophagus from side to side was recorded. The initial
study method had the stylet probe extending to the gastroesophageal (GE)
junction. A revised protocol had the distal end of the endotracheal stylet probe
~4 cm cranial to the GE junction. In six cadavers using the initial study method,
the oesophagus was displaced a mean of 1.8 +/- 0.35 cm to the right and 2 +/-
0.48 cm to the left. In five cadavers, using the revised method, the oesophagus
was displaced by a mean of 2.26 +/- 0.27 cm to the right and 2.3 +/- 0.66 cm to
the left. Conclusion: Mediastinal anatomy, specifically the presence of a loose
connective tissue that attaches the oesophagus to the parietal pericardium
overlying the posterior LA wall will allow for a lateral displacement of the
oesophagus. This should decrease or eliminate the likelihood of thermal injury of
the oesophagus. Using an endotracheal stylet, we investigated the lateral
displacement of the oesophagus in 11 human cadavers. In six with the stylet
extending to the GE junction, the oesophagus was displaced a mean of 3.8 cm. In
five, with stylet 4 cm cranial to the junction, the displacement was 4.56 cm.
PMID- 28419225
TI - Epitope mapping of a new anti-Tn antibody detecting gastric cancer cells.
AB - Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn
antigens (GalNAc-Ser/Thr) binding equally to three dimeric forms of the epitope,
Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of
G2-D11 is minimally influenced by the peptide structure, which indicates a high
degree of carbohydrate epitope dominance and a low influence from the protein
backbone. With a high affinity (KDapp = 1.3 * 10-8 M) and no cross-reactivity to
either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent
candidate for a well-defined anti-Tn-antigen reagent. Detailed
immunohistochemical evaluation of tissue sections from a cohort of 80 patients
with gastric carcinoma showed in all cases positive tumor cells. The observed
staining was localized to the cytoplasm and in some cases to the membrane,
whereas the surrounding tissue was completely negative demonstrating the
usefulness of the novel Tn-antigen binding antibody.
PMID- 28419226
TI - Sugar versus fat: elimination of glycogen storage improves lipid accumulation in
Yarrowia lipolytica.
AB - Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon
storage in most eukaryotic organisms. We investigated the glycogen metabolism of
the oleaginous Y. lipolytica and found that this yeast accumulates up to 16%
glycogen in its biomass. Assuming that elimination of glycogen synthesis would
result in an improvement of lipid accumulation, we characterized and deleted the
single gene coding for glycogen synthase, YlGSY1. The mutant was grown under
lipogenic conditions with glucose and glycerol as substrates and we obtained up
to 60% improvement in TAG accumulation compared to the wild type strain.
Additionally, YlGSY1 was deleted in a background that was already engineered for
high lipid accumulation. In this obese background, TAG accumulation was also
further increased. The highest lipid content of 52% was found after 3 days of
cultivation in nitrogen-limited glycerol medium. Furthermore, we constructed
mutants of Y. lipolytica and S. cerevisiae that are deleted for both glycogen and
TAG synthesis, demonstrating that the ability to store carbon is not essential.
Overall, this work showed that glycogen synthesis is a competing pathway for TAG
accumulation in oleaginous yeasts and that deletion of the glycogen synthase has
beneficial effects on neutral lipid storage.
PMID- 28419228
TI - Native aortic valve thrombosis in patient with protein S deficiency.
AB - Native aortic valve thrombosis is an extremely rare condition, the causes of
which include previous aortic valve diseases, endocarditis, valvular injury by a
catheter intervention and an underlying hypercoagulative state. Its diagnosis is
important for preventing life-threatening embolic complications. Here, we report
a case of native aortic valve thrombosis and recurrent systemic embolism in a
patient with protein S deficiency, a disorder associated with a hypercoagulative
state.
PMID- 28419227
TI - Neural Programmatic Role of Leptin, TNFalpha, Melanocortin, and Glutamate in
Blood Pressure Regulation vs Obesity-Related Hypertension in Male C57BL/6 Mice.
AB - Continuous nutritional surplus sets the stage for hypertension development.
Whereas moderate dietary obesity in mice is normotensive, the homeostatic balance
is disrupted concurrent with an increased risk of hypertension. However, it
remains unclear how the obesity-associated prehypertensive state is converted
into overt hypertension. Here, using mice with high-fat-diet (HFD)-induced
moderate obesity vs control diet (CD)-fed lean mice, we comparatively studied the
effects of central leptin and tumor necrosis factor-alpha (TNFalpha) as well as
the involvement of the neuropeptide melanocortin pathway vs the neurotransmitter
glutamate pathway. Compared with CD-fed lean mice, the pressor effect of central
excess leptin and TNFalpha, but not melanocortin, was sensitized in HFD-fed mice.
The pressor effect of central leptin in HFD-fed mice was strongly suppressed by
glutamatergic inhibition but not by melanocortinergic inhibition. The pressor
effect of central TNFalpha was substantially reversed by melanocortinergic
inhibition in HFD-fed mice but barely in CD-fed mice. Regardless of diet, the
hypertensive effects of central TNFalpha and melanocortin were both partially
reversed by glutamatergic suppression. Hence, neural control of blood pressure is
mediated by a signaling network between leptin, TNFalpha, melanocortin, and
glutamate and changes in dynamics due to central excess leptin and TNFalpha
mediate the switch from normal physiology to obesity-related hypertension.
PMID- 28419229
TI - Non-invasive assessment of cerebral oxygen metabolism following surgery of
congenital heart disease.
AB - OBJECTIVES: Cerebral protection is a major issue in the treatment of infants with
complex congenital heart disease. We tested a new device combining tissue
spectrometry and laser Doppler flowmetry for non-invasive determination of
cerebral oxygen metabolism following cardiac surgery in infants. METHODS: We
prospectively measured regional cerebral oxygen saturation cSO 2 and
microperfusion (rcFlow) in 43 infants 12-24 h following corrective ( n = 30) or
palliative surgery ( n = 13) of congenital heart defects. For comparison,
cerebral blood flow (CBF) was determined by colour duplex sonography of the
extracranial cerebral arteries. Cerebral fractional tissue oxygen extraction,
approximated cerebral metabolic rate of oxygen (aCMRO 2 ) and cerebral metabolic
rate of oxygen (CMRO 2 ) were calculated. RESULTS: cSO 2 was lower [54.6% (35.7
64.0) vs 59.7% (44.5-81.7); P < 0.01] after neonatal palliation, while rcFlow
[69.7 AU (42.5-165.3) vs 77.0 AU (41.2-168.1); P = 0.06] and cerebral fractional
tissue oxygen extraction [0.34 (0.24-0.82) vs 0.38 (0.17-0.55); P = 0.63] showed
a trend towards lower values. We found a positive correlation between aCMRO 2 and
CMRO 2 ( r = 0.27; P = 0.03). aCMRO 2 was significantly lower after neonatal
palliation [4.0 AU (2.1-6.3) vs 4.9 AU (2.2-15.6); P = 0.02]. CONCLUSIONS:
According to our experience, combined photospectrometry and laser Doppler
flowmetry enable non-invasive assessment of cerebral oxygen metabolism. The
method promises new insights into perioperative cerebral perfusion following
palliation or corrective surgery in infancy.
PMID- 28419230
TI - Structuring (right) atrial fibrillation: location matters.
PMID- 28419231
TI - Antibiotic resistance in Staphylococcus aureus. Current status and future
prospects.
AB - The major targets for antibiotics in staphylococci are (i) the cell envelope,
(ii) the ribosome and (iii) nucleic acids. Several novel targets emerged from
recent targeted drug discovery programmes including the ClpP protease and FtsZ
from the cell division machinery. Resistance can either develop by horizontal
transfer of resistance determinants encoded by mobile genetic elements viz
plasmids, transposons and the staphylococcal cassette chromosome or by mutations
in chromosomal genes. Horizontally acquired resistance can occur by one of the
following mechanisms: (i) enzymatic drug modification and inactivation, (ii)
enzymatic modification of the drug binding site, (iii) drug efflux, (iv) bypass
mechanisms involving acquisition of a novel drug-resistant target, (v)
displacement of the drug to protect the target. Acquisition of resistance by
mutation can result from (i) alteration of the drug target that prevents the
inhibitor from binding, (ii) derepression of chromosomally encoded multidrug
resistance efflux pumps and (iii) multiple stepwise mutations that alter the
structure and composition of the cell wall and/or membrane to reduce drug access
to its target. This review focuses on development of resistance to currently used
antibiotics and examines future prospects for new antibiotics and informed use of
drug combinations.
PMID- 28419232
TI - Corrigendum: Time-discounting and tobacco smoking: a systematic review and
network analysis.
PMID- 28419233
TI - Epicardial ablation may not be necessary in all patients with arrhythmogenic
right ventricular dysplasia/cardiomyopathy and frequent ventricular tachycardia:
author's reply.
PMID- 28419234
TI - Copy number alterations assessed at the single-cell level revealed mono- and
polyclonal seeding patterns of distant metastasis in a small-cell lung cancer
patient.
PMID- 28419235
TI - A Bayesian group sparse multi-task regression model for imaging genetics.
AB - Motivation: Recent advances in technology for brain imaging and high-throughput
genotyping have motivated studies examining the influence of genetic variation on
brain structure. Wang et al. have developed an approach for the analysis of
imaging genomic studies using penalized multi-task regression with regularization
based on a novel group l2,1-norm penalty which encourages structured sparsity at
both the gene level and SNP level. While incorporating a number of useful
features, the proposed method only furnishes a point estimate of the regression
coefficients; techniques for conducting statistical inference are not provided. A
new Bayesian method is proposed here to overcome this limitation. Results: We
develop a Bayesian hierarchical modeling formulation where the posterior mode
corresponds to the estimator proposed by Wang et al. and an approach that allows
for full posterior inference including the construction of interval estimates for
the regression parameters. We show that the proposed hierarchical model can be
expressed as a three-level Gaussian scale mixture and this representation
facilitates the use of a Gibbs sampling algorithm for posterior simulation.
Simulation studies demonstrate that the interval estimates obtained using our
approach achieve adequate coverage probabilities that outperform those obtained
from the nonparametric bootstrap. Our proposed methodology is applied to the
analysis of neuroimaging and genetic data collected as part of the Alzheimer's
Disease Neuroimaging Initiative (ADNI), and this analysis of the ADNI cohort
demonstrates clearly the value added of incorporating interval estimation beyond
only point estimation when relating SNPs to brain imaging endophenotypes.
Availability and Implementation: Software and sample data is available as an R
package 'bgsmtr' that can be downloaded from The Comprehensive R Archive Network
(CRAN). Contact: nathoo@uvic.ca. Supplementary information: Supplementary data
are available at Bioinformatics online.
PMID- 28419236
TI - Studying the effect of administration route and treatment dose on the selection
of enrofloxacin resistance in commensal Escherichia coli in broilers.
AB - Objectives: Factors potentially contributing to fluoroquinolone resistance
selection in commensal Escherichia coli strains in poultry were studied through a
series of in vivo experiments. The effect of the initial prevalence of
enrofloxacin resistance in the E. coli gut microbiota, effect of the bacterial
fitness of the enrofloxacin-resistant strain and effect of treatment with
enrofloxacin (effect of dose and effect of route of administration) were
assessed. Methods: Four in vivo studies with broiler chickens were performed.
Right after hatching, the chicks were inoculated with either a bacteriologically
fit or a bacteriologically non-fit fluoroquinolone-resistant strain as either a
minority or the majority of the total E. coli population. Six days later, the
chicks were treated for three consecutive days either orally or parenterally and
using three different doses (under-, correct- and over-dose) of enrofloxacin. The
faecal shedding of E. coli strains was quantified by plating on agar plates
either supplemented or not supplemented with enrofloxacin. Linear mixed models
were used to assess the effect of the aforementioned variables on the selection
of enrofloxacin resistance. Results: The factors that significantly contributed
were treatment ( P < 0.001), bacterial fitness of the resistant donor strain (
P < 0.001), administration route ( P = 0.052) and interactions between
bacterial fitness and administration route ( P < 0.001). Conclusions: In the
currently used models, fluoroquinolone resistance selection was influenced by
treatment, bacterial fitness of the inoculation strain and administration route.
The use of oral treatment seems to select more for fluoroquinolone resistance,
particularly in the model where a non-fit strain was used for inoculation.
PMID- 28419238
TI - Antiretroviral Therapy Initiation and Changes in Self-Reported Depression.
AB - In this retrospective study of treatment-naive PLWH initiating antiretroviral
therapy, the score for the depression scale of the Patient Health Questionnaire
(PHQ-9) was significantly higher at baseline (median, 6.0; interquartile range, 2
11) than at 12 months (3.0; 0-8; P < .001). Baseline depression and lack of
insurance are associated with 12-month depression, but receipt of efavirenz-based
antiretroviral therapy is not.
PMID- 28419239
TI - Quantitative Analysis of Long-Term Mass Rearing of Neoseiulus californicus
(Acari: Phytoseiidae) on Almond Pollen.
AB - Long-term feeding effects of the almond pollen on the life table parameters of
Neoseiulus californicus McGregor were assessed after 5, 10, and 20 generations
after introduction in the rearing arena. Furthermore, to evaluate behavioral
characteristics of the mass-reared predator (strain A) in face with the real
prey, functional and numerical responses of the predator to different densities
of the twospotted spider mite nymphs were determined, and the obtained data were
compared with those reared on twospotted spider mite (strain T). Long-term
rearing did not significantly affect total fecundity of N. californicus (ranged
from 37.79 to 41.91 eggs). Nevertheless, preadult duration in the 5th generation
was significantly longer than the 10th and 20th generations. The intrinsic rate
of increase (r) in the 10th (0.2056 d-1) and 20th (0.2201 d-1) generations had
not significant difference together. However, the r value slightly dropped in the
5th generation (0.1706 d-1) because of the irregular offering of fresh pollen to
the rearing colonies before that. Both strains of N. californicus exhibited a
type II functional response; however, the N. californicus reared on the almond
pollen (strain A) had a higher attack rate (a) and shorter handling time (Th).
The individuals reared on the almond pollen had a greater size than those reared
on twospotted spider mite; its higher predation potential is probably due to this
characteristic. Consequently, the rearing of N. californicus on the almond pollen
positively affected its attributes including high survivorship, body size, and
fecundity, and subsequently higher potential to control twospotted spider mite.
PMID- 28419237
TI - The FAT Score, a Fibrosis Score of Adipose Tissue: Predicting Weight-Loss Outcome
After Gastric Bypass.
AB - Context: Bariatric surgery (BS) induces major and sustainable weight loss in many
patients. Factors predicting poor weight-loss response (PR) need to be identified
to improve patient care. Quantification of subcutaneous adipose tissue (scAT)
fibrosis is negatively associated with post-BS weight loss, but whether it could
constitute a predictor applicable in clinical routine remains to be demonstrated.
Objective: To create a semiquantitative score evaluating scAT fibrosis and test
its predictive value on weight-loss response after Roux-en-Y gastric bypass
(RYGB). Methods: We created a fibrosis score of adipose tissue (FAT score)
integrating perilobular and pericellular fibrosis. Using this score, we
characterized 183 perioperative scAT biopsy specimens from severely obese
patients who underwent RYGB (n = 85 from a training cohort; n = 98 from a
confirmation cohort). PR to RYGB was defined as <28% of total weight loss at 1
year (lowest tertile). The link between FAT score and PR was tested in univariate
and multivariate models. Results: FAT score was directly associated with
increasing scAT fibrosis measured by a standard quantification method (P for
trend <0.001). FAT score interobserver agreement was good (kappa = 0.76). FAT
score >=2 was significantly associated with PR. The association remained
significant after adjustment for age, diabetes status, hypertension, percent fat
mass, and interleukin-6 level (adjusted odds ratio, 3.6; 95% confidence interval,
1.8 to 7.2; P = 0.003). Conclusion: The FAT score is a new, simple,
semiquantitative evaluation of human scAT fibrosis that may help identify
patients with a potential limited weight-loss response to RYGB.
PMID- 28419240
TI - From Nano to Micro: using nanotechnology to combat microorganisms and their
multidrug resistance.
AB - The spread of antibiotic resistance and increasing prevalence of biofilm
associated infections is driving demand for new means to treat bacterial
infection. Nanotechnology provides an innovative platform for addressing this
challenge, with potential to manage even infections involving multidrug-resistant
(MDR) bacteria. The current review summarizes recent progress over the last 2
years in the field of antibacterial nanodrugs, and describes their unique
properties, mode of action and activity against MDR bacteria and biofilms.
Biocompatibility and commercialization are also discussed. As opposed to the more
common division of nanoparticles (NPs) into organic- and inorganic-based
materials, this review classifies NPs into two functional categories. The first
includes NPs exhibiting intrinsic antibacterial properties and the second is
devoted to NPs serving as a cargo for delivering antibacterial agents.
Antibacterial nanomaterials used to decorate medical devices and implants are
reviewed here as well.
PMID- 28419242
TI - Quantifying the impact of rising food prices on child mortality in India: a cross
district statistical analysis of the District Level Household Survey.
PMID- 28419241
TI - Central Hypothyroidism Due to a TRHR Mutation Causing Impaired Ligand Affinity
and Transactivation of Gq.
AB - Context: Central congenital hypothyroidism (CCH) is an underdiagnosed disorder
characterized by deficient production and bioactivity of thyroid-stimulating
hormone (TSH) leading to low thyroid hormone synthesis. Thyrotropin-releasing
hormone (TRH) receptor (TRHR) defects are rare recessive disorders usually
associated with incidentally identified CCH and short stature in childhood.
Objectives: Clinical and genetic characterization of a consanguineous family of
Roma origin with central hypothyroidism and identification of underlying
molecular mechanisms. Design: All family members were phenotyped with thyroid
hormone profiles, pituitary magnetic resonance imaging, TRH tests, and dynamic
tests for other pituitary hormones. Candidate TRH, TRHR, TSHB, and IGSF1 genes
were screened for mutations. A mutant TRHR was characterized in vitro and by
molecular modeling. Results: A homozygous missense mutation in TRHR (c.392T > C;
p.I131T) was identified in an 8-year-old boy with moderate hypothyroidism (TSH:
2.61 mIU/L, Normal: 0.27 to 4.2; free thyroxine: 9.52 pmol/L, Normal: 10.9 to
25.7) who was overweight (body mass index: 20.4 kg/m2, p91) but had normal
stature (122 cm; -0.58 standard deviation). His mother, two brothers, and
grandmother were heterozygous for the mutation with isolated hyperthyrotropinemia
(TSH: 4.3 to 8 mIU/L). The I131T mutation, in TRHR intracellular loop 2,
decreases TRH affinity and increases the half-maximal effective concentration for
signaling. Modeling of TRHR-Gq complexes predicts that the mutation disrupts the
interaction between receptor and a hydrophobic pocket formed by Gq. Conclusions:
A unique missense TRHR defect identified in a consanguineous family is associated
with central hypothyroidism in homozygotes and hyperthyrotropinemia in
heterozygotes, suggesting compensatory elevation of TSH with reduced biopotency.
The I131T mutation decreases TRH binding and TRHR-Gq coupling and signaling.
PMID- 28419243
TI - Efficacy and Safety of Pubertal Induction Using 17beta-Estradiol in Transgirls.
AB - Context: Puberty suppression using gonadotropin-releasing hormone agonists,
followed by induction of the desired sex characteristics using sex steroids, has
been recommended by the current guidelines as the treatment of choice for gender
dysphoric adolescents, although little evidence is available. Aim: To evaluate
the efficacy and safety of estrogen treatment for pubertal induction in
transgirls (female-identifying adolescents assigned male at birth). Methods:
Twenty-eight adolescents treated with oral estrogen for >=1 year were included.
The Tanner stage, anthropometry, laboratory parameters, bone age, and body
composition were evaluated. Results: Breast development started within 3 months
in 83% of adolescents, and after 3 years, 86% had Tanner breast stage 4 to 5. The
hip circumference increased and the waist/hip ratio decreased. The median serum
estradiol was 100 pmol/L (range, 24 to 380) at the standard adult dose of 2 mg of
17beta-estradiol. The adult height standard deviation score was +1.9 (for
females). The body mass index standard deviation score, lean body mass
percentage, fat percentage, and blood pressure did not change. No abnormalities
of creatinine or liver enzymes were detected, and the hematocrit and hemoglobin
A1c did not change. One individual developed hyperprolactinemia during high-dose
ethinylestradiol treatment to limit growth. Conclusions: Pubertal induction using
estradiol is effective; however, an adult dose of 2 mg does not always result in
appropriate serum estradiol levels. Monitoring renal function, liver enzymes,
hematocrit, and hemoglobin A1c during pubertal induction with estradiol is not
necessary. Further studies are needed to establish effective and safe methods to
limit growth.
PMID- 28419245
TI - Support of the aortic wall: a histological study in sheep comparing a macroporous
mesh with low-porosity vascular graft of the same polyethylene terephthalate
material.
AB - OBJECTIVES: Wrapping with various materials was an early treatment for aortic
aneurysms. Wrapping with low-porosity vascular grafts has been associated with
graft migration and vascular erosion. An alternative is to use a macroporous mesh
(MPM) made of the same polymer (polyethylene terephalate). We compared the
histological outcome 1 year after wrapping sheep aortas with low-porosity grafts
versus MPM fabrics. METHODS: The 2 different fabrics were wrapped around the
aorta of 3 sheep. After 1 year the aortas were excised. The 2 wrapped segments of
aorta were compared with each other and control aorta. Histological examinations
and measurements were made of the layers of the aortic wall in 36 prespecified
locations in each of the 3 sheep. RESULTS: Both fabrics were consistently
surrounded by foreign body reaction and well-vascularized fibrosis. This was more
pronounced with the low-porosity vascular graft material which was poorly
incorporated and caused buckling at the transition between wrapped and unwrapped
aorta. Conversely, the MPM was fully incorporated, resulting in a composite
mesh/biological aortic wall. There was reduction of medial thickness with both
materials but it was locally more extreme due to the corrugations in the vascular
graft material. The findings were consistent between sampled locations and were
similar in the 3 animals. CONCLUSIONS: The different porosity and rigidity of the
materials influences their incorporation into the aortic wall. The incorporation
of the pliable MPM precludes the complications of migration and erosion which are
seen after wrapping with low-porosity prosthetic vascular graft material.
PMID- 28419244
TI - Resolvin D1 and D2 Reverse Lipopolysaccharide-Induced Depression-Like Behaviors
Through the mTORC1 Signaling Pathway.
AB - Background: Resolvin D1 and D2 are bioactive lipid mediators that are generated
from docosahexaenoic acid. Although recent preclinical studies suggest that these
compounds have antidepressant effects, their mechanisms of action remain unclear.
Methods: We investigated mechanisms underlying the antidepressant effects of
resolvin D1 and resolvin D2 in lipopolysaccharide (0.8 mg/kg, i.p.)-induced
depression model mice using a tail suspension test. Results: I.c.v. infusion of
resolvin D1 (10 ng) and resolvin D2 (10 ng) produced antidepressant effects;
these effects were significantly blocked by a resolvin D1 receptor antagonist
WRW4 (10 ug, i.c.v.) and a resolvin D2 receptor antagonist O-1918 (10 ug,
i.c.v.), respectively. The mammalian target of rapamycin complex 1 inhibitor
rapamycin (10 mg/kg, i.p.) and a mitogen-activated protein kinase kinase
inhibitor U0126 (5 ug, i.c.v.) significantly blocked the antidepressant effects
of resolvin D1 and resolvin D2. An AMPA receptor antagonist NBQX (10 mg/kg, i.p.)
and a phosphoinositide 3-kinase inhibitor LY294002 (3 ug, i.c.v.) blocked the
antidepressant effects of resolvin D1 significantly, but not of resolvin D2.
Bilateral infusions of resolvin D1 (0.3 ng/side) or resolvin D2 (0.3 ng/side)
into the medial prefrontal cortex or dentate gyrus of the hippocampus produced
antidepressant effects. Conclusions: These findings demonstrate that resolvin D1
and resolvin D2 produce antidepressant effects via the mammalian target of
rapamycin complex 1 signaling pathway, and that the medial prefrontal cortex and
dentate gyrus are important brain regions for these antidepressant effects. These
compounds and their receptors may be promising targets for the development of
novel rapid-acting antidepressants, like ketamine and scopolamine.
PMID- 28419246
TI - Quality assurance for a multicenter Phase II study of stereotactic ablative
radiotherapy for hepatocellular carcinoma <=5 cm: a planning dummy run.
AB - Objective: The Korean Radiation Oncology Group (12-02) investigated the outcome
of stereotactic ablative radiotherapy for hepatocellular carcinoma <=5 cm using
60 Gy in three fractions. To evaluate dosimetric differences and compliance in a
multicenter trial, a planning dummy run procedure was performed. Methods: All six
participating institutions were provided the contours of two dummy run cases.
Plans were performed following the study protocol to cover the planning target
volume with a minimum of 90% of the prescription dose and to satisfy the
constraints for organs at risk. We assessed the institutional variations in plans
using dose-volume histograms. Results: Different planning techniques were
applied: static intensity-modulated radiotherapy in two institutions, CyberKnife
in two institutions and RapidArc in two institutions. The conformity index of all
12 plans was <=1.2. In terms of the planning target volume coverage, all
participants followed our study protocol. For the second dummy run case, located
in Segment 8 near the heart, the minimum dose of the planning target volume
(D99%: dose covering 99% of the planning target volume) was variable because
there was no mention of constraints of D99% of the planning target volume in the
study protocol. As an important organ at risk, the normal liver volumes receiving
<17 Gy in all 12 plans were >700 ml. Conclusions: Dosimetric parameters showed
acceptable compliance with the study protocol. However, we found the possibility
of underdose to the planning target volume if the hepatocellular carcinoma lesion
was located near organs at risk such as the heart. Based on this dummy run, we
will conduct individual case reviews to minimize the effects of study protocol
deviation.
PMID- 28419247
TI - Cardioinhibitory and vasodepressor responses to different stressors on head-up
tilt.
PMID- 28419248
TI - Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup
analysis from the CheckMate 025 study.
AB - Background: Nivolumab improved overall survival (OS) and objective response rate
(ORR) versus everolimus in previously treated patients with advanced renal cell
carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We
report efficacy and safety in the global and Japanese populations (minimum follow
up: 26 months). Methods: Patients were randomized 1:1 to receive nivolumab 3
mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily.
Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and
safety. Results: Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26
(6%), respectively, were Japanese. Median OS for the global population was 26.0
months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence
interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese
patients. ORR for the global population was 26% (nivolumab) versus 5%
(everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43%
versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade
treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most
common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most
common, hypertriglyceridemia [12%]) treated with everolimus; the most common with
nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of
life was stable in the nivolumab arm. Conclusions: With >2 years of follow-up,
Japanese patients had a higher response rate with nivolumab versus everolimus
that was more pronounced yet consistent with the global population, with median
OS not reached, and a favorable safety profile.
PMID- 28419249
TI - Cohort Profile: African Collaborative Center for Microbiome and Genomics
Research's (ACCME's) Human Papillomavirus (HPV) and Cervical Cancer Study.
PMID- 28419250
TI - Enhanced glycolysis, regulated by HIF-1alpha via MCT-4, promotes inflammation in
arsenite-induced carcinogenesis.
AB - Arsenite is well established as a human carcinogen, but the molecular mechanisms
leading to arsenite-induced carcinogenesis are complex and elusive. Accelerated
glycolysis, a common process in tumor cells called the Warburg effect, is
associated with various biological phenomena. However, the role of glycolysis
induced by arsenite is unknown. We have found that, with chronic exposure to
arsenite, L-02 cells undergo a metabolic shift to glycolysis. In liver cells
exposed to arsenite, hypoxia inducible factor-1alpha (HIF-1alpha) and
monocarboxylate transporter-4 (MCT-4) are over-expressed. MCT-4, directly
mediated by HIF-1alpha, maintains a high level of glycolysis, and the enhanced
glycolysis promotes pro-inflammatory properties, which are involved in arsenite
carcinogenesis. In addition, serum lactate and cytokines are higher in arsenite
exposed human populations, and there is a positive correlation between them.
Moreover, there is a positive relationship between lactate and cytokines with
arsenic in hair. In sum, these findings indicate that MCT-4, mediated by HIF
1alpha, enhances the glycolysis induced by arsenite. Lactate, the end product of
glycolysis, is released into the extracellular environment. The acidic
microenvironment promotes production of pro-inflammatory cytokines, which
contribute to arsenite-induced liver carcinogenesis. These results provide a link
between the induction of glycolysis and inflammation in liver cells exposed to
arsenite, and thus establish a previously unknown mechanism for arsenite-induced
hepatotoxicity.
PMID- 28419252
TI - Sensitive Determination of Cannabinoids in Whole Blood by LC-MS-MS After Rapid
Removal of Phospholipids by Filtration.
AB - Direct analysis of Delta9-tetrahydrocannabinol (THC) and other cannabinoids in
crude acetonitrile extracts of whole blood by liquid chromatography-tandem mass
spectrometry using pneumatically assisted electrospray ionization (LC-ESI-MS-MS)
was subjected to pronounced ion suppression from co-eluting phospholipids (PLs).
The interferences were mainly caused by the lysophosphatidylcholine and
lysophosphatidylethanolamine classes of PLs. The PLs were easily removed from
crude extracts by filtration through a sorbent with Lewis acid properties, which
typically increased the THC and cannabinol (CBN) signal intensities by a factor
of 5. Based on this technique, a simple high-throughput LC-MS-MS method was
developed for the determination of cannabinoids in 100 MUL samples of whole
blood. The lower limits of quantification were 0.2 MUg/L for THC, CBN,
cannabidiol (CBD) and Delta9-tetrahydrocannabinolic acid A (THCA-A) and 0.5 MUg/L
for 11-hydroxy-Delta9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-Delta9
tetrahydrocannabinol (THC-COOH). The mean ion suppression levels after clean-up
were 10% (THC), 9% (CBN), 17% (CBD), 0% (THC-OH), 2% (THC-COOH) and 9% (THCA-A)
at blood concentration levels of 1-10 MUg/L. The mean true extraction recoveries
were 97% (THC), 101% (CBN), 101% (CBD), 98% (THC-OH), 95% (THC-COOH) and 90%
(THCA-A) at the same concentration levels. The relative intra-laboratory
reproducibility standard deviations were <9% at concentrations of 1 MUg/L or
higher. The trueness expressed as the relative bias of the test results was
within +/-4% at concentrations of 1 MUg/L or higher.
PMID- 28419251
TI - Evaluating genetic variants associated with breast cancer risk in high and
moderate-penetrance genes in Asians.
AB - Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1,
BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes
CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast
cancer. In this study, we investigated whether there are additional variants in
these 13 genes associated with breast cancer among women of Asian ancestry. We
analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and
6624 controls of Asian descent included in the Breast Cancer Association
Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included
in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense
variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser),
rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing
statistically significant associations with breast cancer risk, with P-values of
1.2 * 10-4, 1.0 * 10-3 and 5.0 * 10-3, respectively. In addition, we found four
low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the
BRCA1 gene, one common variant in the CHEK2 gene (rs9620817), and one common
variant in the PALB2 gene (rs13330119) associated with breast cancer risk at P <
0.01. Our study identified several new risk variants in BRCA1, BRCA2, CHEK2, and
PALB2 genes in relation to breast cancer risk in Asian women. These results
provide further insights that, in addition to the high/moderate penetrance
mutations, other low-penetrance variants in these genes may also contribute to
breast cancer risk.
PMID- 28419254
TI - Evidence of Zika Virus RNA Fragments in Aedes albopictus (Diptera: Culicidae)
Field-Collected Eggs From Camacari, Bahia, Brazil.
AB - A major mosquito-borne viral disease outbreak caused by Zika virus (ZIKV)
occurred in Bahia, Brazil, in 2015, largely due to transmission by the mosquito,
Aedes aegypti (L.). Detecting ZIKV in field samples of Ae. aegypti has proven
problematic in some locations, suggesting other mosquito species might be
contributing to the spread of ZIKV. In this study, several (five) adult Aedes
albopictus (Skuse) mosquitoes that emerged from a 2015 field collection of eggs
from Camacari, Bahia, Brazil, were positive for ZIKV RNA; however, attempts to
isolate live virus were not successful. Results from this study suggest that
field-collected Ae. albopictus eggs may contain ZIKV RNA that require further
tests for infectious ZIKV. There is a need to investigate the role of Ae.
albopictus in the ZIKV infection process in Brazil and to study the potential
presence of vertical and sexual transmission of ZIKV in this species.
PMID- 28419255
TI - Unannounced versus announced hospital surveys: a nationwide cluster-randomized
controlled trial.
AB - Objective: To evaluate the effectiveness of unannounced versus announced surveys
in detecting non-compliance with accreditation standards in public hospitals.
Design: A nationwide cluster-randomized controlled trial. Setting and
participants: All public hospitals in Denmark were invited. Twenty-three
hospitals (77%) (3 university hospitals, 5 psychiatric hospitals and 15 general
hospitals) agreed to participate. Intervention: Twelve hospitals were randomized
to receive unannounced surveys (intervention group) and eleven hospitals to
receive announced surveys (control group). We hypothesized that the hospitals
receiving the unannounced surveys would reveal a higher degree of non-compliance
with accreditation standards than the hospitals receiving announced surveys. Nine
surveyors trained and employed by the Danish Institute for Quality and
Accreditation in Healthcare (IKAS) were randomized into teams and conducted all
surveys. Main outcome measure: The outcome was the surveyors' assessment of the
hospitals' level of compliance with 113 performance indicators-an abbreviated set
of the Danish Healthcare Quality Programme (DDKM) version 2, covering
organizational standards, patient pathway standards and patient safety standards.
Compliance with performance indicators was analyzed using binomial regression
analysis with bootstrapped robust standard errors. Results: In all, 16 202
measurements were acceptable for data analysis. The risk of observing non
compliance with performance indicators for the intervention group compared with
the control group was statistically insignificant (risk difference (RD) = -0.6
percentage points [-2.51-1.31], P = 0.54). A converged analysis of the six
patient safety critical standards, requiring 100% compliance to gain
accreditation status revealed no statistically significant difference (RD = -0.78
percentage points [-4.01-2.44], P = 0.99). Conclusions: Unannounced hospital
surveys were not more effective than announced surveys in detecting quality
problems in Danish hospitals. Trial Registration number: ClinicalTrials.gov
NCT02348567, https://clinicaltrials.gov/ct2/show/NCT02348567?term=NCT02348567.
PMID- 28419256
TI - ChloroMitoCU: Codon patterns across organelle genomes for functional genomics and
evolutionary applications.
AB - Organelle genomes are widely thought to have arisen from reduction events
involving cyanobacterial and archaeal genomes, in the case of chloroplasts, or
alpha-proteobacterial genomes, in the case of mitochondria. Heterogeneity in base
composition and codon preference has long been the subject of investigation of
topics ranging from phylogenetic distortion to the design of overexpression
cassettes for transgenic expression. From the overexpression point of view, it is
critical to systematically analyze the codon usage patterns of the organelle
genomes. In light of the importance of codon usage patterns in the development of
hyper-expression organelle transgenics, we present ChloroMitoCU, the first-ever
curated, web-based reference catalog of the codon usage patterns in organelle
genomes. ChloroMitoCU contains the pre-compiled codon usage patterns of 328
chloroplast genomes (29,960 CDS) and 3,502 mitochondrial genomes (49,066 CDS),
enabling genome-wide exploration and comparative analysis of codon usage patterns
across species. ChloroMitoCU allows the phylogenetic comparison of codon usage
patterns across organelle genomes, the prediction of codon usage patterns based
on user-submitted transcripts or assembled organelle genes, and comparative
analysis with the pre-compiled patterns across species of interest. ChloroMitoCU
can increase our understanding of the biased patterns of codon usage in organelle
genomes across multiple clades. ChloroMitoCU can be accessed at:
http://chloromitocu.cgu.edu.tw/.
PMID- 28419257
TI - Rodent-Pika Parasite Spillover in Western North America.
AB - Competition during the Cenozoic expansion of the Rodentia may have contributed to
ecological niche reduction of pikas, which are now increasingly under threat as
their habitat degrades under global climate change, while some rodents expand
their ranges and overlap with pikas. Range overlap carries the possibility of
disease spillover. Contemporary North American pikas are cold-adapted and
relegated primarily to alpine environments where they subsist on relatively low
quality herbaceous diet. Yet their evolutionary ancestors were distributed
geographically even into the subtropics. Here we examine historical and
contemporary records of fleas on pikas (Ochotona princeps) from sites at
different elevations in the Sierra Nevada and Rocky Mountains and the Pacific
Northwest. We calculated indices of diversity from each site and spillover
fraction, i.e., the proportion of fleas on pikas that have a preference for
rodents. Across this range there are four pika specialist flea species, with no
more than two of these per site, and 18 characteristically rodent flea species.
Diversity is greatest in the Pacific Northwest and lowest in Montana. Rodent flea
spillover onto pikas declines with elevation in the Rocky Mountains. These data
provide evidence that rodents and pikas interact enough to allow considerable
parasite spillover, and which could be exacerbated as pikas are increasingly
stressed by climate change at lower elevations some rodent species expand up
elevation in the face of increasing global warming. With global climate change,
both biotic and abiotic niche shrinkage demand our attention.
PMID- 28419258
TI - EigenTHREADER: analogous protein fold recognition by efficient contact map
threading.
AB - Motivation: Protein fold recognition when appropriate, evolutionarily-related,
structural templates can be identified is often trivial and may even be viewed as
a solved problem. However in cases where no homologous structural templates can
be detected, fold recognition is a notoriously difficult problem ( Moult et al.,
2014 ). Here we present EigenTHREADER, a novel fold recognition method capable of
identifying folds where no homologous structures can be identified. EigenTHREADER
takes a query amino acid sequence, generates a map of intra-residue contacts, and
then searches a library of contact maps of known structures. To allow the contact
maps to be compared, we use eigenvector decomposition to resolve the principal
eigenvectors these can then be aligned using standard dynamic programming
algorithms. The approach is similar to the Al-Eigen approach of Di Lena et al.
(2010) , but with improvements made both to speed and accuracy. With this search
strategy, EigenTHREADER does not depend directly on sequence homology between the
target protein and entries in the fold library to generate models. This in turn
enables EigenTHREADER to correctly identify analogous folds where little or no
sequence homology information is. Results: EigenTHREADER outperforms well
established fold recognition methods such as pGenTHREADER and HHSearch in terms
of True Positive Rate in the difficult task of analogous fold recognition. This
should allow template-based modelling to be extended to many new protein families
that were previously intractable to homology based fold recognition methods.
Availability and implementation: All code used to generate these results and the
computational protocol can be downloaded from
https://github.com/DanBuchan/eigen_scripts . EigenTHREADER, the benchmark code
and the data this paper is based on can be downloaded from:
http://bioinfadmin.cs.ucl.ac.uk/downloads/eigenTHREADER/ . Contact:
d.t.jones@ucl.ac.uk.
PMID- 28419260
TI - Mitochondria-targeted small molecule SS31: a potential candidate for the
treatment of Alzheimer's disease.
PMID- 28419259
TI - Adjunctive Corticosteroid Therapy in the Treatment of Coccidioidal Meningitis.
AB - Coccidioidal meningitis (CM) has high morbidity, and adjunctive measures to
improve outcomes are needed. Using an established multicenter retrospective
cohort study of CM (N = 221), we found that patients receiving adjunctive
corticosteroids had a significant reduction in secondary cerebrovascular events
(P = .0049). Those with CM-associated cerebrovascular events (8%) may benefit
from short-term corticosteroids.
PMID- 28419262
TI - Death, disease and indignity: serious health and human rights concerns persist in
UK Immigration Detention Facilities.
PMID- 28419261
TI - Challenges in adapting existing clinical natural language processing systems to
multiple, diverse health care settings.
AB - Objective: Widespread application of clinical natural language processing (NLP)
systems requires taking existing NLP systems and adapting them to diverse and
heterogeneous settings. We describe the challenges faced and lessons learned in
adapting an existing NLP system for measuring colonoscopy quality. Materials and
Methods: Colonoscopy and pathology reports from 4 settings during 2013-2015,
varying by geographic location, practice type, compensation structure, and
electronic health record. Results: Though successful, adaptation required
considerably more time and effort than anticipated. Typical NLP challenges in
assembling corpora, diverse report structures, and idiosyncratic linguistic
content were greatly magnified. Discussion: Strategies for addressing adaptation
challenges include assessing site-specific diversity, setting realistic
timelines, leveraging local electronic health record expertise, and undertaking
extensive iterative development. More research is needed on how to make it easier
to adapt NLP systems to new clinical settings. Conclusions: A key challenge in
widespread application of NLP is adapting existing systems to new clinical
settings.
PMID- 28419263
TI - Renal Toxicity in Pediatric Patients Receiving Cidofovir for the Treatment of
Adenovirus Infection.
AB - Treatment options for adenovirus infection in immunocompromised children are
limited. Nephrotoxicity has been associated with cidofovir use, but the rate of
cidofovir-associated nephrotoxicity in pediatric patients is unclear. In a
retrospective review of patients with adenovirus infection treated with
cidofovir, neonates (n = 5) had higher viral loads and shorter times to renal
insufficiency than older children (n = 24). Higher weekly doses of cidofovir were
associated with greater increases in creatinine levels. Of 29 courses of
cidofovir, 9 were complicated by acute kidney injury; in these children,
mortality was high. Cidofovir dosing in children needs to be optimized, and other
therapeutic alternatives should be developed.
PMID- 28419264
TI - Evaluating the impact of contracting out basic health care services in the state
of Sao Paulo, Brazil.
AB - As a means of dealing with shortcomings in the coverage, quality and efficiency
of the public health care sector, several municipalities in the state of Sao
Paulo, Brazil, have started to contract pre-certified non-profit or non
governmental organizations to take part in the delivery of health care
services.This paper explores the impact of introducing these contracts in the
primary health care sector. Using data on the 645 municipalities in the state of
Sao Paulo and difference-in-differences methods, we estimate the effect of
contracting out in the primary health care sector on various dimensions of
mortality and health care use. The results show that implementation of the
contracting out strategy significantly increases the number of primary health
care appointments by approximately one appointment per user of the national
health care system per year. Point estimates indicate a reducing effect on
hospitalization for preventable diseases.
PMID- 28419266
TI - The Effect of Parasitism and Interpopulation Hybridization on Aedes albopictus
(Diptera: Culicidae) Fitness.
AB - Recent research in mosquito population genetics suggests that interpopulation
hybridization has likely contributed to the rapid spread of the container
breeding mosquitoes. Here, I used laboratory experiments to investigate whether
interpopulation Aedes (Stegomyia) albopictus (Skuse) F1 and F2 hybrids exhibit
higher fitness than parental populations, and whether hybrid mosquito performance
is related to infection by the coevolved protozoan parasite Ascogregarina
taiwanensis (Lien and Levine). Overall, there were significant differences in
development time, wing length, and survival between the two parental mosquito
populations, but no difference in per capita growth rate r. Hybrid mosquitoes
were generally intermediate in phenotype to the parentals, except that F2 females
were significantly larger than the midparent average. In addition, As.
taiwanensis parasites produced fewest oocysts when they were reared in hosts of
hybrid origin. These data suggest that hybridization between previously isolated
mosquito populations can result in slight increases in potential mosquito
reproductive success, via increased hybrid body size, and via the temporary
escape from coevolved parasites. These findings are significant because studies
have shown that even slight hybrid vigor can have positive fitness consequences
for population persistence. Although this was a laboratory experiment extending
only to the F2 generation, many other invasive insects also carry coevolved
parasites, and thus the patterns seen in this mosquito system may be broadly
relevant.
PMID- 28419265
TI - Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis.
AB - What's Known on This Subject: Neonates are at increased risk for developing
sepsis, but this population often exhibits ambiguous clinical signs that
complicate the diagnosis of infection. No biomarker has yet shown enough
diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What
This Study Adds: We show that a gene-expression-based signature is an accurate
objective measure of the risk of sepsis in a neonate or preterm infant, and it
substantially improves diagnostic accuracy over that of commonly used laboratory
based testing. Implementation might decrease inappropriate antibiotic use.
Background: Neonatal sepsis can have devastating consequences, but accurate
diagnosis is difficult. As a result, up to 200 neonates with suspected sepsis are
treated with empiric antibiotics for every 1 case of microbiologically confirmed
sepsis. These unnecessary antibiotics enhance bacterial antibiotic resistance,
increase economic costs, and alter gut microbiota composition. We recently
reported an 11-gene diagnostic test for sepsis (Sepsis MetaScore) based on host
whole-blood gene expression in children and adults, but this test has not been
evaluated in neonates. Methods: We identified existing gene expression microarray
based cohorts of neonates with sepsis. We then tested the accuracy of the Sepsis
MetaScore both alone and in combination with standard diagnostic laboratory tests
in diagnosing sepsis. Results: We found 3 cohorts with a total of 213 samples
from control neonates and neonates with sepsis. The Sepsis MetaScore had an area
under the receiver operating characteristic curve of 0.92-0.93 in all 3 cohorts.
We also found that, as a diagnostic test for sepsis, it outperformed standard
laboratory measurements alone and, when used in combination with another test(s),
resulted in a significant net reclassification index (0.3-0.69) in 5 of 6
comparisons. The mean point estimates for sensitivity and specificity were 95%
and 60%, respectively, which, if confirmed prospectively and applied in a high
risk cohort, could reduce inappropriate antibiotic usage substantially.
Conclusions: The Sepsis MetaScore had excellent diagnostic accuracy across 3
separate cohorts of neonates from 3 different countries. Further prospective
targeted study will be needed before clinical application.
PMID- 28419267
TI - A national survey assessing the number of records allowed open in electronic
health records at hospitals and ambulatory sites.
AB - To reduce the risk of wrong-patient errors, safety experts recommend limiting the
number of patient records providers can open at once in electronic health records
(EHRs). However, it is unknown whether health care organizations follow this
recommendation or what rationales drive their decisions. To address this gap, we
conducted an electronic survey via 2 national listservs. Among 167 inpatient and
outpatient study facilities using EHR systems designed to open multiple records
at once, 44.3% were configured to allow >=3 records open at once (unrestricted),
38.3% allowed only 1 record open (restricted), and 17.4% allowed 2 records open
(hedged). Decision-making centered on efforts to balance safety and efficiency,
but there was disagreement among organizations about how to achieve that balance.
Results demonstrate no consensus on the number of records to be allowed open at
once in EHRs. Rigorous studies are needed to determine the optimal number of
records that balances safety and efficiency.
PMID- 28419268
TI - The American Society for Clinical Pathology's 2015 Wage Survey of Medical
Laboratories in the United States.
AB - Objectives: To inform the pathology and laboratory field of the most recent
national wage data from the American Society for Clinical Pathology (ASCP).
Historically, the results of this biennial survey have served as a basis for
additional research on laboratory recruitment, retention, education, marketing,
certification, and advocacy. Methods: The 2015 wage survey was conducted through
collaboration between the ASCP's Institute of Science, Technology, and Policy in
Washington, DC, and the ASCP Board of Certification in Chicago, Illinois.
Electronic survey invitations were sent to individuals who are currently
practicing in the field. Results: Data reveal increased salaries since 2013 for
all staff-level laboratory professionals surveyed except phlebotomists and
pathologists' assistants. Laboratory assistants and phlebotomists, regardless of
level, continue to have lower salaries while pathologists' assistants and
administration personnel have higher salaries than the rest of the laboratory
professions surveyed. Conclusions: Survey results put emphasis on strategic
recruitment and retention by laboratory training programs and institutions that
hire laboratory professionals.
PMID- 28419269
TI - Dual-Genotype Diffuse Low-Grade Glioma: Is It Really Time to Abandon
Oligoastrocytoma As a Distinct Entity?
AB - We report a unique case of dual-genotype oligoastrocytoma characterized by IDH2
gene mutation. The tumor was resected from the temporal lobe of a 25-year-old
man. At histological examination with hematoxylin and eosin stain, it showed
distinct oligodendroglial and astrocytic areas. The former retained alpha
thalassaemia/mental retardation X-linked (ATRX) immuno-expression and had absent
staining for p53, while the latter had ATRX loss and p53 over-expression.
Molecular analyses were separately assessed in the 2 tumor components. Gene
sequencing disclosed IDH2 mutation in both, whereas oligodendroglial, but not
astrocytic areas, had 1p/19q codeletion and telomerase reverse transcriptase
promoter mutation. Distinction of dual-genotype oligoastrocytoma from
oligodendroglioma and astrocytoma might be clinically relevant for prognosis and
therapy. Because most studies that investigated the molecular phenotype of
oligoastrocytomas have focused on IDH1 R132H mutated cases, we suggest further
analyses on diffuse gliomas with heterogeneous (astrocytic and oligodendroglial)
morphology before oligoastrocytoma is dismissed as a distinct nosological entity.
PMID- 28419270
TI - Raltegravir plus lamivudine as 'maintenance therapy' in suppressed HIV-1-infected
patients in real-life settings.
PMID- 28419271
TI - Genetic testing for familial hypercholesterolaemia is essential in individuals
with high LDL cholesterol: who does it in the world?
PMID- 28419272
TI - Insecticidal and Behavioral Avoidance Responses of Anopheles minimus and Culex
quinquefasciatus (Diptera: Culicidae) to Three Synthetic Repellents.
AB - Escape responses, knockdown (KD), and toxicity of laboratory strains of Anopheles
minimus Theobald and Culex quinquefasciatus Say to three synthetic mosquito
repellents, DEET (N, N-diethyl-3-methylbenzamide), IR3535, or picaridin, at 5%
v/v concentrations, were evaluated using repellent-treated papers in standard WHO
tube assays and an excito-repellency (ER) test chamber system. The tube assays
recorded knockdown effects of each repellent immediately after 30-min exposure
and the final morality following a 24-h holding period. DEET showed 100% KD at 30
min and complete toxicity at 24 h against both species. Both actions were either
minimal or absent for IR3535 and picaridin, respectively. Culex quinquefasciatus
showed significantly greater escape with DEET compared with the other compounds
in both contact irritancy (excitation) and noncontact spatial repellency trials.
Anopheles minimus showed much more pronounced irritancy and repellency flight
escape to IR3535 than picaridin. DEET was the most active irritant and repellent
compound against Cx. quinquefasciatus. When adjusting contact test responses
based on paired noncontact repellency assays, DEET and IR3535 showed much
stronger spatial repellent properties than irritancy with An. minimus. Picaridin
performed poorly as an irritant or repellent against both species. We conclude
that DEET, followed by IR3535, act as strong spatial repellents at 5%
concentration. DEET also performs as a strong toxicant. Our findings show that
different mosquitoes can respond contrastingly to repellents, thus the importance
to test a wider range of species and populations to assess the full range of
chemical action.
PMID- 28419273
TI - Habitat and Density of Oviposition Opportunity Influences Aedes aegypti (Diptera:
Culicidae) Flight Distance.
AB - Understanding the dispersal of Aedes (aegypti (L.) Diptera: Culicidae) after
consuming a potentially infectious bloodmeal is an important part of controlling
the spread of the arboviruses it transmits. Because of the impact on abundance,
removal of oviposition sites is a key component of vector control. However,
source reduction around a case may encourage dispersal of potentially infected
vectors. We compare the effect of oviposition site availability on Ae. aegypti
dispersal behavior within 30-m linear cages in three model ecosystems at the
University of Arizona's Biosphere 2 research facility. We found a significant
interaction effect in which, when oviposition site density was sparse, dispersal
was greater in the highly vegetated humid rainforest and limited in the low
vegetation, arid desert model ecosystem. When oviposition site density was dense,
no significant effect on dispersal was observed. These analyses support the idea
that source reduction has an important influence on the distance that gravid,
potentially infected, females will travel.
PMID- 28419274
TI - Extreme high high-density lipoprotein cholesterol is paradoxically associated
with high mortality in men and women: two prospective cohort studies.
AB - Aims: High-density lipoprotein (HDL) cholesterol concentrations are inversely
associated with cardiovascular disease and mortality across a range of
concentrations, but genetic evidence suggest that extreme high concentrations may
paradoxically lead to more cardiovascular disease. We tested the hypothesis that
extreme high concentrations of HDL cholesterol are associated with high all-cause
mortality in men and women. Methods and results: A total of 52 268 men and 64 240
women were included from the two prospective population-based studies, the
Copenhagen City Heart Study and the Copenhagen General Population Study. During
745 452 person-years of follow-up, number of deaths from any cause were 5619
(mortality rate, 17.1/1000 person-years (95% confidence interval (CI): 16.7
17.6)) in men and 5059 (mortality rate, 12.1/1000 person-years (11.8-12.4)) in
women. The association between HDL cholesterol concentrations and all-cause
mortality was U-shaped for both men and women, with both extreme high and low
concentrations being associated with high all-cause mortality risk. The
concentration of HDL cholesterol associated with the lowest all-cause mortality
was 1.9 mmol/L (95% CI: 1.4-2.0) (73 mg/dL (54-77)) in men and 2.4 mmol/L (1.8
2.5) (93 mg/dL (69-97)) in women. When compared with the groups with the lowest
risk, the multifactorially adjusted hazard ratios for all-cause mortality were
1.36 (95% CI: 1.09-1.70) for men with HDL cholesterol of 2.5-2.99 mmol/L (97-115
mg/dL) and 2.06 (1.44-2.95) for men with HDL cholesterol >=3.0 mmol/L (116
mg/dL). For women, corresponding hazard ratios were 1.10 (0.83-1.46) for HDL
cholesterol of 3.0-3.49 mmol/L (116-134 mg/dL) and 1.68 (1.09-2.58) for HDL
cholesterol >=3.5 mmol/L (135 mg/dL). Conclusion: Men and women in the general
population with extreme high HDL cholesterol paradoxically have high all-cause
mortality. These findings need confirmation in other studies.
PMID- 28419275
TI - Clinical Care Guideline for Improving Pediatric Acute Musculoskeletal Infection
Outcomes.
AB - Background: Acute pediatric musculoskeletal infections are common, leading to
significant use of resources and antimicrobial exposure. In order to decrease
variability and improve the quality of care, Children's Hospital Colorado
implemented a clinical care guideline (CCG) for these infections. The purpose of
this study is to evaluate clinical and resource outcomes PRE and POST this CCG.
Methods: Retrospective chart review evaluated patients admitted to a large
pediatric quaternary referral center (CHCO) diagnosed with acute osteomyelitis,
septic arthritis, pyomyositis, and/or musculoskeletal abscess prior to and after
guideline implementation. Primary outcomes included length of stay and overall
antibiotic use, with additional secondary clinical, process, and therapeutic
outcomes examined. Results: 82 patients were identified in both the pre-CCG and
post-CCG cohorts. There was a reduction in the median of all primary outcomes,
including length of stay (0.6 median days decrease, P = .04), length of IV
antibiotic therapy (4.9 median days decrease, P < .0001), and days of IV
antibiotic therapy (6.4 median days decrease, P = .0004). Our median length of
stay post-CCG was 4.9 days, the shortest reported length of stay for pediatric
acute musculoskeletal infections to date. Additionally, there was a 24.5 hour
reduction in median length of fever (P = .02), faster CRP normalization (P <
.0001), 50% decrease in the number of related readmissions (P = .02), 34%
decrease in central venous catheters placed (P < .0001), decreased time to first
culture (P = .02), and 79% pathogen identification post-CCG (P = .056).
Conclusions: Implementation of a CCG for acute musculoskeletal infections
improves patient, process and resource outcomes.
PMID- 28419276
TI - Molecular Features of the V1-V4 Coding Region of Sexually Transmitted Human
Immunodeficiency Virus Type 1.
AB - Background.: Investigations into which human immunodeficiency virus type 1 (HIV
1) sequence features may be selected for transmission during sexual exposure have
been hampered by the small number of characterized transmission pairs in
individual studies. Methods.: To boost statistical power to detect differences in
glycosylation, length, and electrical charge in the HIV-1 V1-V4 coding region, we
reanalyzed all available 2485 env sequences derived from 114 subjects
representing 58 transmission pairs from previous studies using mixed-effects
linear regression and an approach to approximate the unobserved transmitted
virus. Results.: The recipient partner had a shorter V1-V4 region and fewer
potential N-linked glycosylation sites (PNGS) than sequences from the source
partner. We also detected a trend toward more PNGS and lower isoelectric points
in transmitted sequences with source partner and the evolutionary tendency to
shorten V1-V4 sequences, reduce the number of PNGS, and lower isoelectric points
in the recipient following transmission. Conclusions.: By using all available
well-characterized env sequences from transmission pairs via sexual exposure, we
were able to identify several important virologic factors that may be important
in the development of biomedical preventive interventions.
PMID- 28419277
TI - Prevention of TB using rifampicin plus isoniazid reduces nevirapine
concentrations in HIV-exposed infants.
AB - Background: Newborns of HIV-infected mothers are given daily doses of nevirapine
to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive
TB preventive therapy. TB preventive regimens include isoniazid for 6 months or
rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of
concomitant RH preventive therapy on nevirapine concentrations in infants is
unknown. Patients and methods: Tshepiso was a prospective case-control cohort
study of pregnant HIV-infected women with and without TB whose newborn infants
received standard doses of nevirapine for HIV prophylaxis. Infants born to
mothers with TB also received RH preventive therapy. Infant plasma nevirapine
concentrations were measured at 1 and 6 weeks. The effects of RH preventive
therapy on nevirapine disposition were investigated in a population
pharmacokinetic model. Results: Of 164 infants undergoing pharmacokinetic
sampling, 46 received RH preventive therapy. After adjusting for weight using
allometric scaling, the model estimated a 33% reduction in nevirapine trough
concentrations with RH preventive therapy compared with TB-unexposed infants not
receiving concomitant rifampicin and a 30% decline in trough concentrations in a
typical infant between day 7 and 35 post-partum. Conclusions: Rifampicin-based TB
preventative treatment reduces nevirapine concentrations significantly in HIV
exposed infants. Although the nevirapine exposures required to prevent HIV
acquisition in breastfeeding infants are undefined, given the potential risks
associated with underdosing nevirapine in this setting, it is prudent to avoid
rifampicin-based preventive therapy in HIV-exposed children receiving
prophylactic nevirapine.
PMID- 28419278
TI - Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co
regulation as a predictor of prostate cancer recurrence.
PMID- 28419279
TI - Primates, Lice and Bacteria: Speciation and Genome Evolution in the Symbionts of
Hominid Lice.
AB - Insects with restricted diets rely on symbiotic bacteria to provide essential
metabolites missing in their diet. The blood-sucking lice are obligate, host
specific parasites of mammals and are themselves host to symbiotic bacteria. In
human lice, these bacterial symbionts supply the lice with B-vitamins. Here, we
sequenced the genomes of symbiotic and heritable bacterial of human, chimpanzee,
gorilla, and monkey lice and used phylogenomics to investigate their evolutionary
relationships. We find that these symbionts have a phylogenetic history
reflecting the louse phylogeny, a finding contrary to previous reports of
symbiont replacement. Examination of the highly reduced symbiont genomes (0.53
0.57 Mb) reveals much of the genomes are dedicated to vitamin synthesis. This is
unchanged in the smallest symbiont genome and one that appears to have been
reorganized. Specifically, symbionts from human lice, chimpanzee lice, and
gorilla lice carry a small plasmid that encodes synthesis of vitamin B5, a
vitamin critical to the bacteria-louse symbiosis. This plasmid is absent in an
old world monkey louse symbiont, where this pathway is on its primary chromosome.
This suggests the unique genomic configuration brought about by the plasmid is
not essential for symbiosis, but once obtained, it has persisted for up to 25 My.
We also find evidence that human, chimpanzee, and gorilla louse endosymbionts
have lost a pathway for synthesis of vitamin B1, whereas the monkey louse
symbiont has retained this pathway. It is unclear whether these changes are
adaptive, but they may point to evolutionary responses of louse symbionts to
shifts in primate biology.
PMID- 28419280
TI - Fractional flow reserve and pressure-bounded coronary flow reserve to predict
outcomes in coronary artery disease.
AB - Aims: Fractional flow reserve (FFR) has proven to its prognostic and therapeutic
value. However, the additive prognostic value of coronary flow reserve (CFR)
remains unclear. This study sought to investigate the clinical utility of
combined FFR and CFR measurements to predict outcomes. Methods and results: Using
the prospective, multicentre Interventional Cardiology Research Incooperation
Society-FFR registry, a total of 2088 lesions from 1837 patients were included in
this substudy. Based on baseline and hyperaemic pressure gradients, we computed
physiologic limits of CFR [the so called pressure-bounded (pb) CFR] and
classified lesions as low (<2) or high (>=2). The primary endpoint was major
adverse cardiac events (MACE, a composite of cardiac death, myocardial
infarction, and revascularization) analysed on a per-patient basis. During a
median follow-up of 1.9 years (inter-quartile range: 1.0-3.0 years), MACE
occurred in 5.7% of patients with FFR <=0.80 vs. 2.8% of patients with FFR >0.80
[adjusted hazard ratio (aHR): 2.15, 95% confidence interval (CI): 1.19-3.89; P =
0.011. In contrast, the incidence of MACE did not differ between patients with pb
CFR < 2 vs. pb-CFR >= 2 (4.2% vs. 4.2%; aHR: 0.98, CI: 0.60 to 1.58; P = 0.92).
Incorporation of FFR significantly improved model prediction of MACE (global chi2
38.8-48.1, P = 0.002). However, pb-CFR demonstrated no incremental utility to
classify outcomes (global chi2 48.1-48.2, P > 0.99). Conclusions: In this large,
prospective registry of over 2000 coronary lesions, FFR was strongly associated
with clinical outcomes. In contrast, a significant association between pb-CFR and
clinical events could not be determined and adding knowledge of pb-CFR did not
improve prognostication over FFR alone.
PMID- 28419281
TI - Expression of the Plasmodium falciparum Clonally Variant clag3 Genes in Human
Infections.
AB - Background: Many genes of the malaria parasite Plasmodium falciparum show
clonally variant expression regulated at the epigenetic level. These genes
participate in fundamental host-parasite interactions and contribute to adaptive
processes. However, little is known about their expression patterns during human
infections. A peculiar case of clonally variant genes are the 2 nearly identical
clag3 genes, clag3.1 and clag3.2, which mediate nutrient uptake and are linked to
resistance to some toxic compounds. Methods: We developed a procedure to
characterize the expression of clag3 genes in naturally infected patients and in
experimentally infected human volunteers. Results: We provide the first
description of clag3 expression during human infections, which revealed mutually
exclusive expression and identified the gene predominantly expressed. Adaptation
to culture conditions or selection with a toxic compound resulted in isolate
dependent changes in clag3 expression. We also found that clag3 expression
patterns were reset during transmission stages. Conclusions: Different
environment conditions select for parasites with different clag3 expression
patterns, implying functional differences between the proteins encoded. The
epigenetic memory is likely erased before parasites start infection of a new
human host. Altogether, our findings support the idea that clonally variant genes
facilitate the adaptation of parasite populations to changing conditions through
bet-hedging strategies.
PMID- 28419282
TI - Autologous Haematopoietic Stem Cell Transplantation for Refractory Crohn's
Disease: Efficacy in a Single-Centre Cohort.
AB - Background: Haematopoietic stem cell transplantation [HSCT] is considered a
therapeutic option for patients with severe Crohn's disease [CD] unresponsive to
currently available therapies. Methods: Autologous HSCT was considered for CD
patients with active disease, unresponsive or intolerant to approved medications
and unsuitable for surgery. After HSCT, patients were closely followed up every 6
weeks during the first 2 years and every 6 months thereafter up to 5 years.
Colonoscopy and/or magnetic resonance imaging were performed at Months 6, 12, 24,
and 48 after HSCT. Results: From December 1, 2007 to December 31, 2015, 37 CD
patients were assessed for HSCT. Of these, 35 patients [13 within the ASTIC
trial] underwent mobilisation. Six patients did not complete the transplant for
various reasons and 29 patients were finally transplanted. Patients were followed
up during a median of 12 months [6-60]. At 6 months, 70% of patients achieved
drug-free clinical remission (Crohn's Disease Index of Severity [CDAI] < 150).
The proportion of patients in drug-free remission (CDAI < 150, Simple Endoscopic
activity Score [SES]-CD < 7] was 61% at 1 year, 52% at 2 years, 47% at 3 years,
39% at 4 years, and 15% at 5 years. Patients who relapsed were re-treated and 80%
regained clinical remission. Six out of the 29 [21%] required surgery. One
patient died due to systemic cytomegalovirus infection 2 months after transplant.
Conclusions: HSCT is a salvage therapy for patients with extensive and refractory
CD. Although relapse occurs in a majority of patients within 5 years after
transplant, drug responsiveness is regained and clinical remission achieved in
80% of cases.
PMID- 28419283
TI - DNA-Based Identification of Forensically Important Blow Flies (Diptera:
Calliphoridae) From India.
AB - Correct species identification is the first and the most important criteria in
entomological evidence-based postmortem interval (PMI) estimation. Although
morphological keys are available for species identification of adult blow flies,
keys for immature stages are either lacking or are incomplete. In this study,
cytochrome oxidase subunit 1 (COI) reference data were developed from nine
species (belonging to three subfamilies, namely, Calliphorinae, Luciliinae, and
Chrysomyinae) of blow flies from India. Seven of the nine species included in
this study were found suitable for DNA-based identification using COI gene,
because they showed nonoverlapping intra- (0.0-0.3%) and inter-(1.96-18.14%)
specific diversity, and formed well-supported monophyletic clade in phylogenetic
analysis. The remaining two species (i.e., Chrysomya megacephala (Fabricius) and
Chrysomya chani Kurahashi) cannot be distinguished reliably using our database
because they had a very low interspecific diversity (0.11%), and Ch. megacephala
was paraphyletic with respect to Ch. chani in the phylogenetic analysis. We
conclude that the COI gene is a useful marker for DNA-based identification of
blow flies from India.
PMID- 28419284
TI - Laser Thermal Ablation for Metastases Failing Radiosurgery: A Multicentered
Retrospective Study.
AB - BACKGROUND: Radiosurgical failure following stereotactic radiosurgery for brain
metastases can be attributed to tumor regrowth or radiation necrosis. MRI-guided
laser thermal ablation (LTA) therapy has emerged as an option for treatment;
however, previous literature demonstrates variable results across centers.
OBJECTIVE: To assess the outcomes of LTA in the treatment of metastases failing
radiosurgery across multiple centers and to determine if any treatment factors
are predictive of outcome. METHODS: Clinical data for 30 patients across 4
centers were retrospectively reviewed. Patients were included if they received
LTA therapy following radiosurgical failure due to radiation necrosis or tumor
regrowth. Demographics, surgical data, and follow-up imaging and clinical
information were collected. Linear regression analyses were performed to
determine treatment factors that were associated with post-LTA outcome. RESULTS:
The large majority of patients responded favorably to LTA treatment with low
complication rates (23%), short length of stay (53% <= 2 d) and reductions in
perilesional edema (63%). A total of 73.3% of patients stopped steroids and 48%
saw improvement of their preoperative symptoms. Patients with better pre-LTA
Karnofsky Performance Status had better survival. Patients who had lesions with
more perilesional T2 change post-LTA had a better chance of weaning off steroids
and obtaining symptomatic relief. CONCLUSION: MRI-guided laser thermal ablation
therapy serves as a viable alternative to traditional treatment options for
metastatic brain lesions failing radiosurgery. Although this study is limited by
size and is retrospective, LTA therapy may result in symptomatic improvement and
a more prominent reduction in fluid-attenuated inversion-recovery signal for
larger lesions.
PMID- 28419285
TI - Genomic differentiation and demographic histories of Atlantic and Indo-Pacific
yellowfin tuna (Thunnus albacares) populations.
AB - Recent developments in the field of genomics have provided new and powerful
insights into population structure and dynamics that are essential for the
conservation of biological diversity. As a commercially highly valuable species,
the yellowfin tuna (Thunnus albacares) is intensely exploited throughout its
distribution in tropical oceans around the world, and is currently classified as
near threatened. However, conservation efforts for this species have so far been
hampered by limited knowledge of its population structure, due to incongruent
results of previous investigations. Here, we use whole-genome sequencing in
concert with a draft genome assembly to decipher the global population structure
of the yellowfin tuna, and to investigate its demographic history. We detect
significant differentiation of Atlantic and Indo-Pacific yellowfin tuna
populations as well as the possibility of a third diverged yellowfin tuna group
in the Arabian Sea. We further observe evidence for past population expansion as
well as asymmetric gene flow from the Indo-Pacific to the Atlantic.
PMID- 28419286
TI - Horizontal inequity in outpatient care use and untreated morbidity: evidence from
nationwide surveys in India between 1995 and 2014.
AB - Equity in healthcare has been a long-term guiding principle of health policy in
India. We estimate the change in horizontal inequities in healthcare use over two
decades comparing the older population (60 years or more) with the younger
population (under 60 years). We used data from the nationwide healthcare surveys
conducted in India by the National Sample Survey Organization in 1995-96 and 2014
with sample sizes 633 405 and 335 499, respectively. Bivariate and multivariate
logit regression analyses were used to study the socioeconomic differentials in
self-reported morbidity (SRM), outpatient care and untreated morbidity.
Deviations in the degree to which healthcare was distributed according to need
were measured by horizontal inequity index (HI). In each consumption quintile the
older population had four times higher SRM and outpatient care rate than the
younger population in 2014. In 1995-96, the pro-rich inequity in outpatient care
was higher for the older (HI: 0.085; 95% CI: 0.066, 0.103) than the younger
population (0.039; 0.034, 0.043), but by 2014 this inequity became similar.
Untreated morbidity was concentrated among the poor; more so for the older (
0.320; -0.391, -0.249) than the younger (-0.176; -0.211, -0.141) population in
2014. The use of public facilities increased most in the poorest and poor
quintiles; the increase was higher for the older than the younger population in
the poorest (1.19 times) and poor (1.71 times) quintiles. The use of public
facilities was disproportionately higher for the poor in 2014 than in 1995-96 for
the older (-0.189; -0.234, -0.145 vs - 0.065; -0.129, -0.001) and the younger (
0.145; -0.175, -0.115 vs - 0.056; -0.086, -0.026) population. The older
population has much higher morbidity and is often more disadvantaged in obtaining
treatment. Health policy in India should pay special attention to equity in
access to healthcare for the older population.
PMID- 28419287
TI - Prediction Algorithm for Surgical Intervention in Neonatal Brachial Plexus Palsy.
AB - BACKGROUND: Neonatal brachial plexus palsy (NBPP) results in reduced function of
the affected arm with profound ramifications on quality of life. Advances in
surgical technique have shown improvements in outcomes for appropriately selected
patients. Patient selection, however, remains difficult. OBJECTIVE: To develop a
decision algorithm that could be applied at the individual patient level, early
in life, to reliably predict persistent NBPP that would benefit from surgery.
METHODS: Retrospective review of NBPP patients was undertaken. Maternal and
neonatal factors were entered into the C5.0 statistical package in R (The R
Foundation). A 60/40 model was employed, whereby 60% of randomized data were used
to train the decision tree, while the remaining 40% were used to test the
decision tree. The outcome of interest for the decision tree was a severe lesion
meeting requirements for surgical candidacy. RESULTS: A decision tree prediction
algorithm was generated from the entered variables. Variables utilized in the
final decision tree included presence of Horner's syndrome, presence of a
pseudomeningocele, Narakas grade, clavicle fracture at birth, birth weight >9
lbs, and induction or augmentation of labor. Sensitivity of the decision tree was
0.71, specificity 0.96, positive predictive value 0.94, negative predictive value
0.79, and F1 score 0.81. CONCLUSION: We developed a decision tree prediction
algorithm that can be applied shortly after birth to determine surgical candidacy
of patients with NBPP, the first of its kind utilizing only maternal and neonatal
factors. This conservative decision tree can be used to offer early surgical
intervention for appropriate candidates.
PMID- 28419288
TI - Editor's Note: Transitions at the JNEN.
PMID- 28419289
TI - Parkinson's disease: patient and general practitioner perspectives on the role of
primary care.
AB - Background: Specialized Parkinson's disease (PD) care offers advantages to
patients. However, specialized health care providers may be unaware of patients'
personal context and comorbidity, leading to conflicting treatment regimens.
Patients may benefit from a more holistic approach. Objective: To clarify the
role community-dwelling PD patients see for general practitioners (GPs) in PD
care and to clarify the role GPs see for themselves. Methods: Qualitative
interview study with 16 community-dwelling PD patients and 12 GPs in the
Netherlands, using a constant comparative approach to analysis. Results: Patients
expressed a preference for self-management and autonomy in decision-making. GPs
chose a limited, reactive position in early-stage PD care to stimulate patient
autonomy. Moreover, GPs felt insufficiently competent to extend their role.
Patients also felt GPs lack expert knowledge and skills; they focus on their
neurologist for PD care. In addition, GPs observed patients might not realize
what accessory role the GP could have, a role GPs described as essential in being
aware of patient's well-being. Patients did not describe additional roles for the
GP in more advanced disease, whereas GPs mentioned a shift towards a more
proactive and extended role. Conclusion: Patients and GPs see a limited role for
the GP in early-stage PD care because of patient autonomy and GP's lack of
specific knowledge and skills. However, GPs should feel more confident of the
added value of their generalist approach to care for patients with a complex
chronic disorder as PD. If generalist and specialized care reinforce each other,
PD patients benefit.
PMID- 28419290
TI - SVMQA: support-vector-machine-based protein single-model quality assessment.
AB - Motivation: The accurate ranking of predicted structural models and selecting the
best model from a given candidate pool remain as open problems in the field of
structural bioinformatics. The quality assessment (QA) methods used to address
these problems can be grouped into two categories: consensus methods and single
model methods. Consensus methods in general perform better and attain higher
correlation between predicted and true quality measures. However, these methods
frequently fail to generate proper quality scores for native-like structures
which are distinct from the rest of the pool. Conversely, single-model methods do
not suffer from this drawback and are better suited for real-life applications
where many models from various sources may not be readily available. Results: In
this study, we developed a support-vector-machine-based single-model global
quality assessment (SVMQA) method. For a given protein model, the SVMQA method
predicts TM-score and GDT_TS score based on a feature vector containing
statistical potential energy terms and consistency-based terms between the actual
structural features (extracted from the three-dimensional coordinates) and
predicted values (from primary sequence). We trained SVMQA using CASP8, CASP9 and
CASP10 targets and determined the machine parameters by 10-fold cross-validation.
We evaluated the performance of our SVMQA method on various benchmarking
datasets. Results show that SVMQA outperformed the existing best single-model QA
methods both in ranking provided protein models and in selecting the best model
from the pool. According to the CASP12 assessment, SVMQA was the best method in
selecting good-quality models from decoys in terms of GDTloss. Availability and
implementation: SVMQA method can be freely downloaded from
http://lee.kias.re.kr/SVMQA/SVMQA_eval.tar.gz. Contact: jlee@kias.re.kr.
Supplementary information: Supplementary data are available at Bioinformatics
online.
PMID- 28419291
TI - From systemic and pulmonary hypertension to heart failure: novel drugs and
devices.
PMID- 28419292
TI - Design and Testing of 2 Novel Scores That Predict Global Sagittal Alignment
Utilizing Cervical or Lumbar Plain Radiographs.
AB - BACKGROUND: Global sagittal deformity is an established cause of disability.
However, measurements of sagittal alignment are often ignored when patients
present with symptoms localizing to the cervical or lumbar spine. OBJECTIVE: To
develop scoring scales to predict the risk of sagittal malalignment in patients
with only cervical or lumbar spine radiographs. METHODS: A retrospective review
of a prospectively maintained multicenter adult spinal deformity database was
performed. Primary outcome (sagittal malalignment) was defined as a C7 plumbline
>= 50 mm. Two multivariate logistic regressions were performed using patient
characteristics and measurements derived from cervical or lumbar radiographs as
covariates. Point scores were assigned to age, body mass index (BMI), and lumbar
lordosis or T1 slope by rounding their beta coefficients to the nearest integer.
RESULTS: Nine hundred seventy-nine patients were included, with 652 randomly
assigned to the derivation cohort (used to build the score) and 327 comprising
the validation set. Final cervical score for the primary outcome included BMI >=
25 (1 point), age >= 55 yr (2 points), and T1 slope >= 27o (2 points). Final
lumbar score for the primary outcome included BMI >= 25 (1 point), age >= 55 yr
(1 point), and lumbar lordosis >= 45o (-1 points). High scores for both the
cervical and lumbar spine presented with high specificity and positive likelihood
ratios of sagittal malalignment. CONCLUSION: We developed scoring scales to
predict global sagittal malalignment utilizing clinical covariates and cervical
or lumbar radiographs. Patients with high scores may prompt imaging with long
cassette plain films to evaluate for global sagittal imbalance.
PMID- 28419293
TI - Expression and Enzyme Activity of Catalase in Chilo suppressalis (Lepidoptera:
Crambidae) Is Responsive to Environmental Stresses.
AB - Catalase (CAT) is an important antioxidant enzyme that protects organisms against
oxidative stresses by eliminating hydrogen peroxide. In this study, we cloned and
characterized a full-length cDNA of CAT from Chilo suppressalis (CsCAT) and
examined the influence of environmental stresses on CsCAT expression and enzyme
activity. The cDNA contains a 1659-bp open reading frame encoding a polypeptide
of 553 amino acids most closely related (90.14%) to Papilio polytes catalases.
The CsCAT was expressed in all developmental stages with the highest expression
in the fat body, and the CsCAT enzyme activity closely mirrored its observed mRNA
expression patterns. The CsCAT mRNA was up-regulated when the larvae were exposed
to high temperature (>=30 degrees C), insecticides (abamectin and
chlorantraniliprole), chemicals (H2O2, CHP, CdCl2, and CuSO4), and a dead-end
trap plant (vetiver grass), and the CsCAT enzyme activity again mirrored the
observed CsCAT expression patterns. These results suggest that up-regulation of
CsCAT may enhance the defense response of C. suppressalis by weakening the
effects of environmental stresses, and provide insight into the role of CsCAT
during development of C. suppressalis.
PMID- 28419294
TI - Preliminary Study of Tirofiban Infusion in Coil Embolization of Ruptured
Intracranial Aneurysms.
AB - BACKGROUND: There have been some reports on the use of intra-arterial tirofiban
in ruptured intracranial aneurysms, but few studies have reported on the use of
24 h of intravenous tirofiban infusion in patients with subarachnoid hemorrhage.
OBJECTIVE: To present our experience with intravenous tirofiban infusion, in the
form of a monotherapy as well as in addition to intra-arterial tirofiban, as a
prophylactic, and as a rescue management for thrombus in patients who have
undergone embolization with coils for ruptured intracranial aneurysms. METHODS:
Between December 2008 and January 2015, we retrospectively reviewed 249 ruptured
intracranial aneurysms that were treated with coiling at our institutions. A
total of 28 patients harboring 28 ruptured and 3 unruptured intracranial
aneurysms underwent intravenous tirofiban infusion during or after coil
embolization of an aneurysm. Intra-arterial infusion of tirofiban via a
microcatheter was also performed in 26 patients. RESULTS: Thromboembolic
formation during the procedure was detected in 25 cases. Intra-arterial tirofiban
dissolved the thromboembolus under angiographic control after 10 or more minutes
in 19 (76%) of 25 patients. Two intracranial hemorrhagic complications (increase
in the extent of hematoma) occurred during the follow-up period. Two cases of
other complications occurred: hematuria and perioral bleeding. CONCLUSION:
Intravenous tirofiban, as a monotherapy or in addition to intra-arterial
tirofiban for thrombotic complications, seems to be useful as a treatment for
acute aneurysm. However, alternatives to tirofiban should be considered if an
associated hematoma is discovered before a patient receives a tirofiban infusion.
PMID- 28419295
TI - Anatomic Features of Paraclinoid Aneurysms: Computed Tomography Angiography Study
of 144 Aneurysms in 136 Consecutive Patients.
AB - BACKGROUND: Paraclinoid aneurysms are among the most challenging aneurysms to
treat. Computed tomography (CT) angiography helps in evaluating the radiological
characteristics of these aneurysms next to bony structures. OBJECTIVE: To present
the CT angiography characteristics of paraclinoid aneurysms in order to better
understand such pathology. METHODS: The study examined CT angiography-based
anatomical characteristics obtained retrospectively from 136 patients with 144
paraclinoid aneurysms selected from single-defined catchment populations in
Finland. We examined the diameters of the parent artery (internal carotid
artery), the location of the aneurysm, its dimensions (width, height, neck), and
aneurysm wall irregularity. RESULTS: We analyzed 144 paraclinoid aneurysms in 136
patients admitted to the hospital during 2000-2014. Multivariable analysis
reveals that rupture aneurysms have the following radiological features: aneurysm
larger than 5 mm in diameter (P = .006), irregular wall (P = .046), superior
location, larger aspect ratio (P = .039), and neck wider than parent artery (P <
.001). CONCLUSION: Smaller diameter of the internal carotid artery and superior
location, as well as a large and irregular aneurysm wall, are radiological
characteristics of ruptured paraclinoid aneurysms, which CT angiography can
measure easily.
PMID- 28419297
TI - Host Pore-Forming Protein Complex Neutralizes the Acidification of Endocytic
Organelles to Counteract Intracellular Pathogens.
AB - Many intracellular pathogens invade cells via endocytic organelles and have
adapted to the drop in pH along the endocytic pathway. However, the strategy by
which the host cell counteracts this pathogen adaptation remains unclear.
betagamma-CAT is an aerolysin-like pore-forming protein and trefoil factor
complex in the frog Bombina maxima. We report here that betagamma-CAT, as a host
secreted factor with an intrinsic channel-forming property, is the first example
of a molecule that actively neutralizes the acidification of endocytic organelles
to counteract Listeria monocytogenes infection. Immunodepletion of endogenous
betagamma-CAT largely impaired the control of L. monocytogenes by frog cells.
betagamma-CAT elevates the pH of L. monocytogenes-containing vacuoles to limit
the vacuole escape of L. monocytogenes to cytosol. Furthermore, betagamma-CAT
promotes intracellular L. monocytogenes clearance via autophagy and by that the
nonlytic expulsion of the bacteria from host cells. Finally, betagamma-CAT
attenuated the dissemination of L. monocytogenes in vivo. These findings reveal a
novel host strategy and effectors that combat pathogen adaptation to acidic
conditions along the endocytic pathway.
PMID- 28419296
TI - Urinary podocyte and TGF-beta1 mRNA as markers for disease activity and
progression in anti-glomerular basement membrane nephritis.
AB - Background: Podocyte depletion causes glomerulosclerosis, with persistent
podocyte loss being a major factor driving disease progression. Urinary podocyte
mRNA is potentially useful for monitoring disease progression in both animal
models and in humans. To determine whether the same principles apply to
crescentic glomerular injury, a rat model of anti-glomerular basement membrane
(anti-GBM) nephritis was studied in parallel with a patient with anti-GBM
nephritis. Methods: Podocyte loss was measured by Wilms' Tumor 1-positive
podocyte nuclear counting and density, glomerular epithelial protein 1 or
synaptopodin-positive podocyte tuft area and urinary podocyte mRNA excretion
rate. Glomerulosclerosis was evaluated by Azan staining and urinary transforming
growth factor (TGF)-beta1 mRNA excretion rate. Results: In the rat model,
sequential kidney biopsies revealed that after a threshold of 30% podocyte loss,
the degree of glomerulosclerosis was linearly associated with the degree of
podocyte depletion, compatible with podocyte depletion driving the sclerotic
process. Urinary podocyte mRNA correlated with the rate of glomerular podocyte
loss. In treatment studies, steroids prevented glomerulosclerosis in the anti-GBM
model in contrast to angiotensin II inhibition, which lacked a protective effect,
and urinary podocyte and TGF-beta1 mRNA markers more accurately reflected both
the amount of podocyte depletion and the degree of glomerulosclerosis compared
with proteinuria under both scenarios. In a patient successfully treated for anti
GBM nephritis, urinary podocyte and TGB-beta1 mRNA reflected treatment efficacy.
Conclusion: These results emphasize the role of podocyte depletion in anti-GBM
nephritis and suggest that urinary podocyte and TGF-beta1 mRNA could serve as
markers of disease progression and treatment efficacy.
PMID- 28419298
TI - Cardiac autotransplantation for repair of left ventricular rupture after mitral
valve replacement.
AB - Left ventricular rupture is an infrequent but potentially fatal complication of
mitral valve replacement. Here, we report a case of large posterior mid
ventricular rupture following mitral valve replacement, which was successfully
treated by a sandwich style repair and autotransplantation.
PMID- 28419299
TI - Pregnancy and Labor Complications in Female Survivors of Childhood Cancer: The
British Childhood Cancer Survivor Study.
AB - Background: Female survivors of childhood cancer treated with abdominal
radiotherapy who manage to conceive are at risk of delivering premature and low
birthweight offspring, but little is known about whether abdominal radiotherapy
may also be associated with additional complications during pregnancy and labor.
We investigated the risk of developing pregnancy and labor complications among
female survivors of childhood cancer in the British Childhood Cancer Survivor
Study (BCCSS). Methods: Pregnancy and labor complications were identified by
linking the BCCSS cohort (n = 17 980) to the Hospital Episode Statistics (HES)
for England. Relative risks (RRs) of pregnancy and labor complications were
calculated by site of radiotherapy treatment (none/abdominal/cranial/other) and
other cancer-related factors using log-binomial regression. All statistical tests
were two-sided. Results: A total of 2783 singleton pregnancies among 1712 female
survivors of childhood cancer were identified in HES. Wilms tumor survivors
treated with abdominal radiotherapy were at threefold risk of hypertension
complicating pregnancy (relative risk = 3.29, 95% confidence interval [CI] = 2.29
to 4.71), while all survivors treated with abdominal radiotherapy were at risk of
gestational diabetes mellitus (RR = 3.35, 95% CI = 1.41 to 7.93) and anemia
complicating pregnancy (RR = 2.10, 95% CI = 1.27 to 3.46) compared with survivors
treated without radiotherapy. Survivors treated without radiotherapy had similar
risks of pregnancy and labor complications as the general population, except
survivors were more likely to opt for an elective cesarean section (RR = 1.39,
95% CI = 1.16 to 1.70). Conclusions: Treatment with abdominal radiotherapy
increases the risk of developing hypertension complicating pregnancy in Wilms
tumor survivors, and diabetes mellitus and anemia complicating pregnancy in all
survivors. These patients may require extra vigilance during pregnancy.
PMID- 28419300
TI - Short-term mechanical circulatory support for cardiogenic shock in severe
peripartum cardiomyopathy: La Pitie-Salpetriere experience.
AB - OBJECTIVES: Mechanical circulatory support (MCS) is a valuable option in the
setting of cardiogenic shock (CS), although MCS use in severe forms of peripartum
cardiomyopathy (PPCM) is underreported. We aimed to investigate maternal outcomes
under MCS for refractory CS complicating PPCM. METHODS: We retrospectively
reviewed 10 consecutive patients (2010-2015) meeting diagnosis criteria of PPCM
that were managed with peripheral veno-arterial extracorporeal membrane
oxygenation (pVA-ECMO) for severe CS. RESULTS: Median age was 29 years (range 20
36), and median left ventricular (LV) ejection fraction was 10% (range 5-30). All
patients received femoro-femoral cannulation. All patients were implanted after
delivery. Central rescue cannulation was considered in 5 patients in the setting
of peripheral ECMO-related complications. Median peripheral support duration was
4 days (range 2-25), median central support duration was 51 days (range 9-180).
Five patients died under central support. Three patients were successfully
explanted after LV recovery, and 2 were successfully transplanted. CONCLUSIONS:
Peripheral VA-ECMO, and prompt conversion to central rescue cannulation when
necessary have to be considered in the management of severe cases of PPCM.
Nevertheless, refractory CS in this specific population remains a life
threatening condition despite aggressive management.
PMID- 28419301
TI - Nitrogen use efficiency in crops: lessons from Arabidopsis and rice.
AB - Application of chemical fertilizers, especially nitrogen (N), to crops has
increased dramatically in the last half century and therefore developing crop
varieties with improved N use efficiency (NUE) is urgent for sustainable
agriculture. N utilization procedures generally can be divided into uptake,
transport, and assimilation. Transporters for nitrate or ammonium acquisition and
enzymes for assimilation are among the essential components determining NUE, and
many transcription factors also play a pivotal role in regulating N use
associated genes, thereby contributing to NUE. Although some efforts in improving
NUE have been made in various plants, the regulatory mechanisms underlying NUE
are still elusive, and NUE improvement in crop breeding is very limited. In this
review, the crucial components involved in N utilization and the candidates with
the potential for NUE improvement in dicot Arabidopsis and monocot rice are
summarized. In addition, strategies based on new techniques which can be used for
dissecting regulatory mechanisms of NUE and also the possible ways in which NUE
can be improved in crops are discussed.
PMID- 28419302
TI - The Posthuman as Hollow Idol: A Nietzschean Critique of Human Enhancement.
AB - In this paper, the author aims to show that transhumanists are confused about
their own conception of the posthuman: transhumanists anticipate radical
transformation of the human through technology and at the same time assume that
the criteria to determine what is "normal" and what is "enhanced" are univocal,
both in our present time and in the future. Inspired by Nietzsche's notion of the
Overhuman, the author argues that the slightest "historical and phenomenological
sense" discloses copious variations of criteria, both diachronic and synchronic,
for what can be considered "normal" and "enhanced." Radical transformation
through technology does not simply enable us to become "stronger," "smarter," or
"healthier," but it can and often will also change the very standard or yardstick
with which we measure what counts as "stronger," "smarter," or "healthier." Put
yet differently: new and emerging technologies are not neutral means but often
bring about different and, from our current perspective, foreign standards for
determining what are "normal" and "enhanced" capacities. Since the qualitative
meanings of these terms are themselves not fixed, it is unintelligible and too
reassuring to simply predict that new technologies will enhance human beings.
PMID- 28419304
TI - Incorporating a Modified Graeb Score to the Modified Fisher Scale for Improved
Risk Prediction of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid
Hemorrhage.
AB - BACKGROUND: Delayed cerebral ischemia (DCI) is a cause of poor outcome after
aneurysmal subarachnoid hemorrhage. Risk scales to predict DCI have scarcely been
evaluated for predictive accuracy. Accounting for volume of intraventricular
hemorrhage (IVH) in the modified Fischer scale (mFS) may improve its predictive
accuracy. OBJECTIVE: To compare the modified Graeb score (mGS) to the mFS for
risk prediction of DCI, and to investigate whether incorporating an mGS cut-point
into the mFS could improve predictive accuracy. METHODS: This retrospective
analysis was based on the Clazosentan to Overcome Neurological Ischemia and
Infarction Occurring after Subarachnoid Hemorrhage (CONSCIOUS-1) trial cohort.
IVH volume was quantified with the mGS. The relation of the mGS to DCI was
evaluated using logistic regression and the area under the receiver operator
characteristics curve (AUC). An optimized mGS cut-point was identified using the
Youden index, and was incorporated into the mFS to dichotomize grades 2 and 4.
The AUC was used to compare the predictive performance of the mGS with that of
the mFS, and to assess whether there was an improvement in DCI prediction after
creation of the dichotomized scale. RESULTS: The mFS and the mGS had similar
discrimination for DCI (AUC: 0.608 vs 0.618; P = .79). A new scale including both
the mFS and mGS significantly improved the AUC compared to the mFS (AUC: 0.647 vs
0.608; P = .022). CONCLUSION: The mFS and the mGS have similar prognostic
utility. Accounting for IVH volume improved prediction of DCI by the mFS.
PMID- 28419303
TI - Tumor microtubes convey resistance to surgical lesions and chemotherapy in
gliomas.
AB - Background: Primary and adaptive resistance against chemo- and radiotherapy and
local recurrence after surgery limit the benefits from these standard treatments
in glioma patients. Recently we found that glioma cells can extend ultra-long
membrane protrusions, "tumor microtubes" (TMs), for brain invasion,
proliferation, and interconnection of single cells to a syncytium that is
resistant to radiotherapy. We wondered whether TMs also convey resistance to the
other 2 standard treatment modalities. Methods: Patient-derived glioblastoma
stemlike cell (GBMSC) lines were implanted under a cranial window in mice.
Longitudinal in vivo two-photon laser scanning microscopy was used to follow
tumor growth, including the fate of single glioma cells over months. Results:
After a cylindrical surgical lesion, GBMSCs increasingly extended TMs toward the
lesion area, which contributed to the repopulation of this area over many weeks.
In fact, an excessive "healing response" was observed in which tumor cell
densities significantly exceeded those of unlesioned brain regions over time.
Inhibition of TM formation and function by genetic targeting of growth associated
protein-43 robustly suppressed this surgery-induced tumor growth reaction, in
contrast to standard postsurgical anti-inflammatory treatment with dexamethasone.
After one cycle of temozolomide chemotherapy, intra- and intertumoral
heterogeneity of TM formation and interconnection was strongly associated with
therapy response: when tumor cells were integrated in TM networks, they were more
likely to resist chemotherapy. Conclusion: TMs can contribute to the resistance
against standard treatment modalities in gliomas. Specific inhibition of TMs is a
promising approach to reduce local recurrence after surgery and lower resistance
to chemotherapy.
PMID- 28419305
TI - Selection for juvenile body weight in chickens: Standardizing for scaling.
AB - The influence of scaling on phenotypic responses to long-term selection was
evaluated in lines of chickens selected for high (HWS) and low (LWS) 8-week body
weight. The focus of the experiment was on phenotypic correlations between means
and standard deviations, and unadjusted vs. standardized responses. Traits
measured were body weight at 4 (BW4) and 8 wk (BW8). Correlations between means
and standard deviations for BW8 (the selected trait) were positive and greater
for BW4 in LWS than HWS. In both lines, scaling masked the degree more than the
pattern of response; however, after standardization, it was greater in LWS than
HWS. Selection changed the standard deviation units of juvenile BW with a 2-fold
difference in BW8 for both HWS and LWS in which the latter reached a
physiological limit. Standardization is a robust method to adjust for scaling,
thus enhancing the interpretability of responses in long-term selection
experiments. Because of changes in variances associated with those in phenotypic
means, this method to correct for part-whole correlations was useful.
PMID- 28419306
TI - Metformin and cancer in type 2 diabetes: a systematic review and comprehensive
bias evaluation.
PMID- 28419307
TI - Truth or Spin? Disease Definition in Cancer Screening.
AB - Are the small and indolent cancers found in abundance in cancer screening normal
variations, risk factors, or disease? Naturalists in philosophy of medicine turn
to pathophysiological findings to decide such questions objectively. To
understand the role of pathophysiological findings in disease definition, we must
understand how they mislead in diagnostic reasoning. Participants on all sides of
the definition of disease debate attempt to secure objectivity via reductionism.
These reductivist routes to objectivity are inconsistent with the Bayesian nature
of clinical reasoning; when they appeal to the sciences, they are inconsistent
with what philosophy of biology tells us about its natural kinds. Proposals that
we narrow the scope of our claims in the disease definition debates (proposing
adoption of a specific disease paradigm for a specific context) are useful, but
paradigms can still distort our reasoning in particular cases, even when we are
self-conscious about their status.
PMID- 28419309
TI - Influence of dietary inclusion of untreated or heat-treated Jatropha meal on
productive and reproductive performances and biochemical blood parameters of
laying Japanese quail.
AB - Jatropha meal (JM) has been characterized as a potential animal feedstuff due to
its high crude protein content and high levels of essential amino acids. However,
it contains anti-nutritive and toxic compounds that may hinder its use. The
present study was conducted to evaluate the effects of a dietary inclusion of raw
Jatropha meal (RJM) and heat-treated Jatropha meal on the growth and production
of laying Japanese quail using productive, reproductive, and biochemical blood
parameters. A total number of 180 mature Japanese quail at 2 months of age (120
females and 60 males) was randomly divided into 4 treatment groups: control (0%
JM); 3.5% RJM; 3.5% JM heated in an oven at 100 degrees C for 24 h (JM24); and
3.5% JM heated in oven at 100 degrees C for 48 h (JM48). After 8 wk on treatment
diets, the inclusion of RJM to quail diets reduced (P < 0.05) feed intake, feed
efficiency, egg number, and egg mass compared with the control diet. There was no
difference between the heat-treated Jatropha (JM24 and JM48) treatments and the
control. Fertility and hatchability percentages were improved (P < 0.001) with
JM24 and JM48 compared with the RJM group. Feeding of 3.5% RJM or JM24 in quail
diets led to significant decrease (P < 0.05) in serum total protein, albumen,
globulin, gamma-glutamyl transpeptidase, total and HDL-cholesterol,
immunoglobulin (IgG and IgM), and increased serum alanine transaminase (ALT) and
creatinine along with the mortality rate when compared with birds fed JM48. In
conclusion, heat treatment of JM is essential to eliminate its hepatotoxic and
nephrotoxic effects and, when properly heat-treated, can be used in laying
Japanese quail diets without detrimental effects on production, reproductive
performance, and health status.
PMID- 28419308
TI - Brain invasion in meningiomas-clinical considerations and impact of
neuropathological evaluation: a systematic review.
AB - With the release of the 2016 edition of the World Health Organization (WHO)
Classification of Central Nervous System Tumors, brain invasion in meningiomas
has been added as a stand-alone criterion for atypia and can therefore impact
grading and indirectly adjuvant therapy. Regarding this rising clinical
importance, we have reviewed the current knowledge about brain invasion with
emphasis on its implications on current and future clinical practice. We found
various definitions of brain invasion and approaches for evaluation in surgically
obtained specimens described over the past decades. This heterogeneity is
reflected by weak correlation with prognosis and remains controversial.
Similarly, associated clinical factors are largely unknown. Preoperative, imaging
guided detection of brain invasion is unspecific, and intraoperative assessment
using standard and new high-magnification microscopic techniques remains
imprecise. Despite the increasing knowledge about molecular alterations of the
tumor/ brain surface, pharmacotherapeutic options targeting brain invasive
meningiomas are lacking. Finally, we summarize the impact of brain invasion on
histopathological grading in the WHO classifications of brain tumors since
1979.In conclusion, standardized neurosurgical sampling and neuropathological
analyses could improve diagnostic reliability and reproducibility of future
studies. Further research is needed to improve pre- and intraoperative
visualization of brain invasion and to develop adjuvant, targeted therapies.
PMID- 28419310
TI - Calmodulin as a Ca2+-Sensing Subunit of Arabidopsis Cyclic Nucleotide-Gated
Channel Complexes.
AB - Ca2+ serves as a universal second messenger in eukaryotic signaling pathways, and
the spatial and temporal patterns of Ca2+ concentration changes are determined by
feedback and feed-forward regulation of the involved transport proteins. Cyclic
nucleotide-gated channels (CNGCs) are Ca2+-permeable channels that interact with
the ubiquitous Ca2+ sensor calmodulin (CaM). CNGCs interact with CaMs via diverse
CaM-binding sites, including an IQ-motif, which has been identified in the C
termini of CNGC20 and CNGC12. Here we present a family-wide analysis of the IQ
motif from all 20 Arabidopsis CNGC isoforms. While most of their IQ-peptides
interacted with conserved CaMs in yeast, some were unable to do so, despite high
sequence conservation across the family. We showed that the CaM binding ability
of the IQ-motif is highly dependent on its proximal and distal vicinity. We
determined that two alanine residues positioned N-terminal to the core IQ
sequence play a significant role in CaM binding, and identified a polymorphism at
this site that promoted or inhibited CaM binding in yeast. Through detailed
biophysical analysis of the CNGC2 IQ-motif, we found that this polymorphism
specifically affected the Ca2+-independent interactions with the C-lobe of CaM.
This same polymorphism partially suppressed the induction of programmed cell
death by CNGC11/12 in planta. Our work expands the model of CNGC regulation, and
posits that the C-lobe of apo-CaM is permanently associated with the channel at
the N-terminal part of the IQ-domain. This mode allows CaM to function as a Ca2+
sensing regulatory subunit of the channel complex, providing a mechanism by which
Ca2+ signals may be fine-tuned.
PMID- 28419311
TI - In Reply: Carotid Artery Angioplasty and Stenting Without Distal Embolic
Protection Devices.
PMID- 28419312
TI - Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the
Fusion Rates. What is the Optimal Graft Material?
AB - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF)
is an increasingly popular procedure with several potential advantages over
traditional open TLIF. OBJECTIVE: The current study aimed to compare fusion rates
of different graft materials used in MIS-TLIF, via meta-analysis of the published
literature. METHODS: A Medline search was performed and a database was created
including patient's type of graft, clinical outcome, fusion rate, fusion
assessment modality, and duration of follow-up. Meta-analysis of the fusion rate
was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United
Kingdom). RESULTS: A total of 1533 patients from 40 series were included. Fusion
rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess
fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all
recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP
series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion
rate was seen with isolated use of autologous local bone (91.8%). The highest
fusion rate was observed with combination of autologous local bone with bone
extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was
seen with autologous local bone + bone extender (93.1%). The reported
complication rate ranged from 0% to 35.71%. Clinical improvement was observed in
all studies. CONCLUSION: Fusion rates are generally high with MIS-TLIF regardless
of the graft material used. Given the potential complications of iliac bone
harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable.
The highest fusion rate without the use of rhBMP was seen with autologous local
bone plus bone extender (93.1%).
PMID- 28419313
TI - Association between month of birth and melanoma risk: fact or fiction?
PMID- 28419314
TI - Adverse drug reactions during drug-resistant TB treatment in high HIV prevalence
settings: a systematic review and meta-analysis.
AB - Objectives: To estimate the prevalence of adverse drug reactions or events (ADR)
during drug-resistant TB (DR-TB) treatment in the context of settings with high
HIV prevalence (at least 20% of patients). Methods: We conducted a systematic
review and meta-analysis of articles in PubMed and Scopus. Pooled proportions of
patients experiencing adverse events and relative risk with 95% CI were
calculated. Results: The search yielded 24 studies, all observational cohorts.
Ten reported on the number of patients experiencing ADR and were included in the
meta-analysis representing 2776 study participants of whom 1943 were known to be
HIV infected (70.0%). An average of 83% (95% CI: 82%-84%) of patients experienced
one or more ADR. Among the seven articles ( n = 664 study participants) with
information on occurrence of severe ADR, 24% (95% CI: 21%-27%) of patients
experienced at least one severe ADR during drug-resistant TB treatment. Sixteen
of the 24 studies analysed the relative risk of ADR by HIV infection, nine of
which found no statistically significant association between HIV infection and
occurrence of drug-related ADR. There was insufficient information to
disaggregate risk by concomitant treatment with HIV antiretrovirals or by
immunosuppression (CD4 count). Conclusions: No randomized clinical trials were
found for WHO-recommended treatment of drug-resistant TB treatment where at least
20% of the cohort was coinfected with HIV. Nearly all patients (83%) experience
ADR during DR-TB treatment. While no significant association between ADR and HIV
coinfection was found, further research is needed to determine whether
concomitant antiretrovirals or immunosuppression increases the risks for HIV
infected patients.
PMID- 28419315
TI - Clinical Parameters, Routine Inflammatory Markers, and LTA4H Genotype as
Predictors of Mortality Among 608 Patients With Tuberculous Meningitis in
Indonesia.
AB - Background: Damaging inflammation is thought to contribute to the high morbidity
and mortality of tuberculous meningitis (TBM), but the link between inflammation
and outcome remains unclear. Methods: We performed prospective clinical and
routine laboratory analyses of a cohort of adult patients with TBM in Indonesia.
We also examined the LTA4H promoter polymorphism, which predicted cerebrospinal
fluid (CSF) leukocyte count and survival of Vietnamese patients with TBM.
Patients were followed for >1 year. Results: We included 608 patients with TBM,
of whom 67.1% had bacteriological confirmation of disease and 88.2% had severe
(ie, grade II or III) disease. One-year mortality was 43.7% and strongly
associated with decreased consciousness, fever, and focal neurological signs.
Human immunodeficiency virus (HIV) infection, present in 15.3% of patients, was
associated with higher mortality and different CSF characteristics, compared with
absence of HIV infection. Among HIV-uninfected patients, mortality was associated
with higher CSF neutrophil counts (hazard ratio [HR], 1.10 per 10% increase; 95%
confidence interval [CI], 1.04-1.16), low CSF to blood glucose ratio (HR, 1.16
per 0.10 decrease; 95% CI, 1.04-1.30), CSF culture positivity (HR, 1.37; 95% CI,
1.02-1.84), and blood neutrophilia (HR, 1.06 per 109 neutrophils/L increase; 95%
CI, 1.03-1.10). The LTA4H promoter polymorphism correlated with CSF mononuclear
cell count but not with mortality (P = .915). Conclusions: A strong neutrophil
response and fever may contribute to or be a result of (immuno)pathology in TBM.
Aggressive fever control might improve outcome, and more-precise characterization
of CSF leukocytes could guide possible host-directed therapeutic strategies in
TBM.
PMID- 28419316
TI - Effects of Heat Shock on the Bradysia odoriphaga (Diptera: Sciaridae).
AB - Bradysia odoriphaga is frequently subjected to heat shock during the summer in
China. Although the effects of heat shock on insect ecology and physiology have
been widely explored, the effects of heat shock on the life history parameters of
Bradysia odoriphaga are largely unknown. In the present study, we investigated
the effects of heat shock on B. odoriphaga survival and reproduction as well as
on offspring development and sex ratio. We exposed adult B. odoriphaga to 31, 33,
35, or 37 degrees C for different durations (from 0 to 120 min). The results
showed that the survival of both sexes declined with the increase in temperature
and exposure time, especially at 33, 35, and 37 degrees C. Longevity was
markedly greater for males than females across all treatments. Fecundity
generally declined as temperature and exposure time increased, and no eggs
hatched when females were exposed to 37 degrees C for >75 min. The development
of offspring larvae was significantly delayed when the parent female and male had
been exposed to >=31 degrees C for >=30 min. In addition, the sex ratio of F1
progeny derived from heat-shocked parental adults was increasingly skewed to
female as exposure time and temperature treatment increased. Overall, the results
indicate that heat shock negatively influences B. odoriphaga.
PMID- 28419318
TI - DOUBLE-EXPONENTIAL FITTING FUNCTION FOR EVALUATION OF COSMIC-RAY-INDUCED NEUTRON
FLUENCE RATE IN ARBITRARY LOCATIONS.
AB - The fluence rate of cosmic-ray-induced neutrons (CRINs) varies with many
environmental factors. While many current simulation and experimental studies
have focused mainly on the altitude variation, the specific rule that the CRINs
vary with geomagnetic cutoff rigidity (which is related to latitude and
longitude) was not well considered. In this article, a double-exponential fitting
function F=(A1e-A2CR+A3)eB1Al, is proposed to evaluate the CRINs' fluence rate
varying with geomagnetic cutoff rigidity and altitude. The fitting R2 can have a
value up to 0.9954, and, moreover, the CRINs' fluence rate in an arbitrary
location (latitude, longitude and altitude) can be easily evaluated by the
proposed function. The field measurements of the CRINs' fluence rate and H*(10)
rate in Mt. Emei and Mt. Bowa were carried out using a FHT-762 and LB 6411
neutron prober, respectively, and the evaluation results show that the fitting
function agrees well with the measurement results.
PMID- 28419317
TI - High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized,
Multicenter Study.
AB - Context: Increase in drug frequency or dose is recommended for acromegaly
patients with partial response to long-acting somatostatin receptor ligands
(SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN
ATG) at high dose (HD) or high frequency (HF) are still scanty. Objective: To
evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients
with active acromegaly. Design: Twenty-four-week prospective, multicenter,
randomized, open-label trial. Patients and Interventions: Thirty patients with
active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21
days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Outcomes:
Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in
random growth hormone (GH) values < 1.0 ug/L, reduction in serum IGF-I and GH
from baseline, differences in biochemical response between HF and HD LAN-ATG,
adverse events. Results: IGF-I decreased significantly (P = 0.007) during the 24
week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08).
Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs
baseline), without a significant difference between HF and HD groups (P = 0.59).
The decrease in serum IGF-I significantly correlated with serum LAN values (P =
0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P =
0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19
patients (63.3%) experienced adverse events, all being mild to moderate and
transient, without differences between the two therapeutic arms. Conclusion: HF
and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one
third of patients with active acromegaly inadequately controlled by long-term
conventional SRLs therapy.
PMID- 28419319
TI - Influence of concentration, nanoparticle size, beam energy, and material on dose
enhancement in radiation therapy.
AB - The purpose of this study was to analyse the effects of the type, concentration,
and nanoparticle diameter of dose enhancement materials on the dose enhancement
of low- and high-energy megavoltage (MV) X-rays acquired from a medical linear
accelerator using Monte Carlo simulation. Monte Carlo simulation was performed
with the Monte Carlo N-Particle Transport (MCNPX) code, using the energy spectrum
of the linear accelerator and a mathematical Snyder head phantom. A 5-cm-diameter
virtual tumour was defined in the centre of the phantom. Gold, gadolinium, iodine
and iron oxide were used as dose enhancement materials. Varying concentrations
(7, 18 and 30 mg/g) of nanoparticles of different diameters (25, 50, 75, 100 and
125 nm) were applied, and the dose enhancement was comparatively evaluated for 4,
6, 10 and 15 MV X-rays, and a 60Co source. Higher dose enhancement factors (DEFs)
were observed when the incident energy was low. Moreover, the dose enhancement
effects were greatest with gold nanoparticles, followed by gadolinium, iodine,
and iron oxide nanoparticles; the DEFs were 1.011-1.047 (gold), 1.005-1.030
(gadolinium), 1.002-1.028 (iodine) and 1.002-1.014 (iron oxide). The dose
enhancement effects increased with increasing nanoparticle diameter and
concentration. However, the concentration of the material had a greater impact
than the diameter of the nanoparticles. As the concentration and diameter of
nanoparticles increased, the DEF also increased. The 4 and 6 MV X-rays
demonstrated higher dose enhancement compared with the 10 and 15 MV X-rays.
PMID- 28419320
TI - Therapeutic CPAP Level Predicts Upper Airway Collapsibility in Patients With
Obstructive Sleep Apnea.
AB - Study Objectives: Upper airway collapsibility is a key determinant of obstructive
sleep apnea (OSA) which can influence the efficacy of certain non-continuous
positive airway pressure (CPAP) treatments for OSA. However, there is no simple
way to measure this variable clinically. The present study aimed to develop a
clinically implementable tool to evaluate the collapsibility of a patient's upper
airway. Methods: Collapsibility, as characterized by the passive pharyngeal
critical closing pressure (Pcrit), was measured in 46 patients with OSA.
Associations were investigated between Pcrit and data extracted from patient
history and routine polysomnography, including CPAP titration. Results:
Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit
(r2=0.51, p < .001) of all the variables investigated including apnea-hypopnea
index, body mass index, sex, and age. Patients with a mildly collapsible upper
airway (Pcrit <= -2 cmH2O) had a lower therapeutic CPAP level (6.2 +/- 0.6 vs.
10.3 +/- 0.4 cmH2O, p < .001) compared to patients with more severe
collapsibility (Pcrit > -2 cmH2O). A therapeutic CPAP level <=8.0 cmH2O was
sensitive (89%) and specific (84%) for detecting a mildly collapsible upper
airway. When applied to the independent validation data set (n = 74), this
threshold maintained high specificity (91%) but reduced sensitivity (75%).
Conclusions: Our data demonstrate that a patient's therapeutic CPAP requirement
shares a strong predictive relationship with their Pcrit and may be used to
accurately differentiate OSA patients with mild airway collapsibility from those
with moderate-to-severe collapsibility. Although this relationship needs to be
confirmed prospectively, our findings may provide clinicians with better
understanding of an individual patient's OSA phenotype, which ultimately could
assist in determining which patients are most likely to respond to non-CPAP
therapies.
PMID- 28419321
TI - Genetic analysis of partial egg production records in Japanese quail using random
regression models.
AB - The main objectives of this study were to detect the most appropriate random
regression model (RRM) to fit the data of monthly egg production in 2 lines
(selected and control) of Japanese quail and to test the consistency of different
criteria of model choice. Data from 1,200 female Japanese quails for the first 5
months of egg production from 4 consecutive generations of an egg line selected
for egg production in the first month (EP1) was analyzed. Eight RRMs with
different orders of Legendre polynomials were compared to determine the proper
model for analysis. All criteria of model choice suggested that the adequate
model included the second-order Legendre polynomials for fixed effects, and the
third-order for additive genetic effects and permanent environmental effects.
Predictive ability of the best model was the highest among all models (rho =
0.987). According to the best model fitted to the data, estimates of heritability
were relatively low to moderate (0.10 to 0.17) showed a descending pattern from
the first to the fifth month of production. A similar pattern was observed for
permanent environmental effects with greater estimates in the first (0.36) and
second (0.23) months of production than heritability estimates. Genetic
correlations between separate production periods were higher (0.18 to 0.93) than
their phenotypic counterparts (0.15 to 0.87). The superiority of the selected
line over the control was observed through significant (P < 0.05) linear contrast
estimates. Significant (P < 0.05) estimates of covariate effect (age at sexual
maturity) showed a decreased pattern with greater impact on egg production in
earlier ages (first and second months) than later ones. A methodology based on
random regression animal models can be recommended for genetic evaluation of egg
production in Japanese quail.
PMID- 28419322
TI - DOSIMETRIC EVALUATION OF LASER-DRIVEN X-RAY AND NEUTRON SOURCES UTILIZING XG-III
PS LASER WITH PEAK POWER OF 300 TERAWATT.
AB - Current short-pulse high-intensity lasers can accelerate electrons and
proton/ions to energies of giga-electron volts. For certain advanced
applications, laser-accelerated electrons and protons are optimised for high
energy X-ray and neutron generation at the XG-III picosecond (ps) laser beamline.
These energetic X-ray and neutron beams can significantly affect radiation safety
at the facility; therefore, proper evaluation of the radiological hazards induced
by laser-driven X-ray and neutron sources is required. This study presents a
dosimetric evaluation of laser-driven X-ray and neutron sources at the XG-III ps
laser beamline. The 'source terms' of the laser-accelerated electrons and protons
are characterised utilising the particle-in-cell method and an analytical model,
respectively. The Monte Carlo code FLUKA is used to calculate prompt and residual
dose yields due to all radiation field components and the number of residual
activated nuclei. Our results can provide a reference for radiation hazard
analysis at short-pulse high-intensity laser facilities worldwide.
PMID- 28419323
TI - Monte Carlo Simulation Used to Calculate Energy Correction Factor for
Thermoluminescent Dosimeters Used by Occupational Workers on Pediatric Exams.
AB - The main objective of this work is to simulate the X-ray scattered spectra by
different pediatric phantoms (simulation of children subjected to barium meal
procedures) to calculate an energy correction factor (ECF) to the reading of
thermoluminescent dosimeters (TLDs). To perform this evaluation, the TLDs were
positioned over three areas in two occupational workers: eyes, thyroid and hands.
The Geant4 toolkit was used to define the spectra collected by TLDs, making
possible to calculate the ECF. This work was developed in two stages: (1)
evaluation of scattered spectra by different standard phantoms (newborn, 1, 5 and
10 years old); (2) definition of the ECF to the absorbed energy by each TLD.
Geant4 shows to be a good toolkit to calculate the ECF and among the different
characteristics evaluated, in this work, the TLD position and acceleration
voltages are the most significant parameters that may influence the ECF
calculated.
PMID- 28419324
TI - Improving data workflow systems with cloud services and use of open data for
bioinformatics research.
AB - Data workflow systems (DWFSs) enable bioinformatics researchers to combine
components for data access and data analytics, and to share the final data
analytics approach with their collaborators. Increasingly, such systems have to
cope with large-scale data, such as full genomes (about 200 GB each), public fact
repositories (about 100 TB of data) and 3D imaging data at even larger scales. As
moving the data becomes cumbersome, the DWFS needs to embed its processes into a
cloud infrastructure, where the data are already hosted. As the standardized
public data play an increasingly important role, the DWFS needs to comply with
Semantic Web technologies. This advancement to DWFS would reduce overhead costs
and accelerate the progress in bioinformatics research based on large-scale data
and public resources, as researchers would require less specialized IT knowledge
for the implementation. Furthermore, the high data growth rates in bioinformatics
research drive the demand for parallel and distributed computing, which then
imposes a need for scalability and high-throughput capabilities onto the DWFS. As
a result, requirements for data sharing and access to public knowledge bases
suggest that compliance of the DWFS with Semantic Web standards is necessary. In
this article, we will analyze the existing DWFS with regard to their capabilities
toward public open data use as well as large-scale computational and human
interface requirements. We untangle the parameters for selecting a preferable
solution for bioinformatics research with particular consideration to using cloud
services and Semantic Web technologies. Our analysis leads to research guidelines
and recommendations toward the development of future DWFS for the bioinformatics
research community.
PMID- 28419325
TI - Dissecting molecular and physiological response mechanisms to high solar
radiation in cyanic and acyanic leaves: a case study on red and green basil.
AB - Photosynthetic performance and the expression of genes involved in light
signaling and the biosynthesis of isoprenoids and phenylpropanoids were analysed
in green ('Tigullio', TIG) and red ('Red Rubin', RR) basil. The aim was to detect
the physiological and molecular response mechanisms to high sunlight. The
attenuation of blue-green light by epidermal anthocyanins was shown to evoke
shade-avoidance responses with consequential effects on leaf morpho-anatomical
traits and gas exchange performance. Red basil had a lower mesophyll conductance,
partially compensated by the less effective control of stomatal movements, in
comparison with TIG. Photosynthesis decreased more in TIG than in RR in high
sunlight, because of larger stomatal limitations and the transient impairment of
PSII photochemistry. The methylerythritol 4-phosphate pathway promoted above all
the synthesis and de-epoxidation of violaxanthin-cycle pigments in TIG and of
neoxanthin and lutein in RR. This enabled the green leaves to process the excess
radiant energy effectively, and the red leaves to optimize light harvesting and
photoprotection. The greater stomatal closure observed in TIG than in RR was due
to enhanced abscisic acid (ABA) glucose ester deglucosylation and reduced ABA
oxidation, rather than to superior de novo ABA synthesis. This study shows a
strong competition between anthocyanin and flavonol biosynthesis, which occurs at
the level of genes regulating the oxidation of the C2-C3 bond in the dihydro
flavonoid skeleton.
PMID- 28419326
TI - Accessibility to surgical robot technology and prostate-cancer patient behavior
for prostatectomy.
AB - Background: To examine how surgical robot emergence affects prostate-cancer
patient behavior in seeking radical prostatectomy focusing on geographical
accessibility. Methods: In Japan, robotic surgery was approved in April 2012.
Based on data in the Japanese Diagnosis Procedure Combination database between
April 2012 and March 2014, distance to nearest surgical robot and interval days
to radical prostatectomy (divided by mean interval in 2011: % interval days to
radical prostatectomy) were calculated for individual radical prostatectomy cases
at non-robotic hospitals. Caseload changes regarding distance to nearest surgical
robot and robot introduction were investigated. Change in % interval days to
radical prostatectomy was evaluated by multivariate analysis including distance
to nearest surgical robot, age, comorbidity, hospital volume, operation type,
hospital academic status, bed volume and temporal progress. Results: % Interval
days to radical prostatectomy became wider for distance to nearest surgical robot
<30 km. When a surgical robot emerged within 30 and 10 km, the prostatectomy
caseload in non-robot hospitals reduced by 13 and 18% within 6 months,
respectively, while the robot hospitals gained +101% caseload (P < 0.01 for all)
Multivariate analyses including 9759 open and 5052 non-robotic minimally invasive
radical prostatectomies in 483 non-robot hospitals revealed a significant inverse
association between distance to nearest surgical robot and % interval days to
radical prostatectomy (B = -17.3% for distance to nearest surgical robot >=30 km
and -11.7% for 10-30 km versus distance to nearest surgical robot <10 km), while
younger age, high-volume hospital, open-prostatectomy provider and temporal
progress were other significant factors related to % interval days to radical
prostatectomy widening (P < 0.05 for all). Conclusions: Robotic surgery
accessibility within 30 km would make patients less likely select conventional
surgery. The nearer a robot was, the faster the caseload reduction was.
PMID- 28419327
TI - Epilepsy Surgeries Requiring an Operculoinsular Cortectomy: Operative Technique
and Results.
AB - BACKGROUND: Epilepsy surgeries requiring an operculoinsulectomy pose significant
difficulties because the perisylvian area is highly vascular, deep, and
functional. OBJECTIVE: To report the operative technique and results of epilepsy
surgeries requiring an operculoinsular cortectomy at our institution. METHODS:
The data of all consecutive patients who had undergone an epilepsy surgery
requiring an operculoinsular cortectomy with a minimum follow-up of 1 yr were
reviewed. Tumor and vascular malformation cases were excluded. Surgical
techniques are described based on findings during surgery. RESULTS: Twenty-five
patients underwent an epilepsy surgery requiring an operculoinsular cortectomy:
mean age at surgery was 35 y (9-51), mean duration of epilepsy was 19 y (5-36),
14 were female, and mean duration of follow-up was 4.7 y (1-16). Magnetic
resonance imaging of the operculoinsular area was normal or revealed questionable
nonspecific findings in 72% of cases. Investigation with intracranial EEG
electrodes was done in 17 patients. Surgery was performed on the dominant side
for language in 7 patients. An opercular resection was performed in all but 2
patients who only had an insulectomy. Engel class I seizure control was achieved
in 80% of patients. Postoperative neurological deficits (paresis, dysphasia,
alteration of taste, smell, hearing, pain, and thermal perceptions) were frequent
(75%) but always transient except for 1 patient with persistent mild alteration
of thermal and pain perception. CONCLUSION: Surgical treatment of operculoinsular
epilepsy is effective in achieving seizure control and is associated with an
acceptable long-term complication rate.
PMID- 28419328
TI - Efficacy and safety of osimertinib in a Japanese compassionate use program.
AB - Background: Osimertinib is a third-generation epidermal growth factor receptor
(EGFR) tyrosine kinase inhibitor (TKI) that targets the T790M mutation of EGFR.
In 2016, AstraZeneca conducted a compassionate use program for osimertinib in
Japan. Methods: Eighteen consecutive patients with histologically proven non
small-cell lung cancer (NSCLC) and harboring the T790M EGFR mutation participated
in the compassionate use program between 1 April and 25 May 2016, at the National
Cancer Center Hospital. We examined the efficacy and safety of osimertinib in a
compassionate use program. Results: All patients had been previously treated with
both cytotoxic chemotherapy and EGFR TKIs. Overall response rate was 62.5% (95%
confidence interval (CI): 35.9-89.1%). Among the six patients pretreated with a
third-generation EGFR TKI, two (33%) responded to osimertinib. On administration
with osimertinib, median progression-free and overall survival rates at six
months were 66.7% (95% CI: 44.9-88.5) and 88.9% (95% CI: 74.4-100), respectively.
Although the toxicity of osimertinib was mild in most patients, three patients
had severe adverse events: two developed interstitial lung disease (ILD) and one
developed Grade 3 hepatotoxicity. Among these, two (33%) of the six patients who
received osimertinib following nivolumab treatment developed severe adverse
events, with one each developing Grade 3 hepatotoxicity and Grade 3 ILD. Only one
patient visited our hospital seeking to participate in the compassionate program
from another hospital. Conclusion: Osimertinib demonstrated efficacy even in
patients with heavily pretreated NSCLC harboring the T790M mutation. Some
patients pretreated with another third-generation EGFR TKI also responded to
osimertinib.
PMID- 28419329
TI - Effects of the inclusion of a Bacillus direct-fed microbial on performance
parameters, bone quality, recovered gut microflora, and intestinal morphology in
broilers consuming a grower diet containing corn distillers dried grains with
solubles.
AB - Distillers dried grains with solubles (DDGS) have increasingly been used in
poultry diets as a consequence of rising grain costs. Some, but not all, sources
of DDGS have a variable compositional value, and a high inclusion of this by
product could be considered a risk factor for presentation of enteric diseases.
Presently, 2 experiments were conducted using a starter corn-soybean diet (zero
to 7 d) and a corn-DDGS-soybean grower diet (8 to 28 d) with or without inclusion
of a Bacillus-direct-fed microbial (DFM). In both experiments, day-of-hatch
chicks were randomly assigned to 2 different groups: control group without DFM or
Bacillus-DFM group, containing 106 spores/g of feed. In each experiment, 8 pens
of 20 chicks (n = 160/group) were used. Performance parameters of BW, BW gain
(BWG), feed intake (FI), and feed conversion (FCR) were evaluated in each growth
phase. Additionally, in experiment 2, intestinal samples were collected to
determine duodenal and ileal morphology (n = 8/group), as well as the microbiota
population of total lactic acid bacteria (TLAB), total Gram-negative bacteria
(TGNB), and total anaerobic bacteria (TAB) on d 28 (n = 16/group). Furthermore,
both tibias were evaluated for bone strength and bone composition (n = 16/group).
In both experiments BW, BWG, and FCR were improved by the DFM when compared to
the control group (P < 0.05). In experiment 2, chickens supplemented with the DFM
had less TGNB in the foregut intestinal segment and higher TLAB counts in both
foregut and hindgut sections (P < 0.05). In addition significant increases in
tibia breaking strength and bone mineralization were observed in the DFM group
when compared with the control. In the case of intestinal morphology, DFM dietary
inclusion increased villus height (VH), villus width, villus area, muscular
thickness, and the VH to crypt depth ratio (VH:CD) in both duodenum and ileum
sections. Results of the present study suggest that consumption of a selected
Bacillus-DFM producing a variable set of enzymes could contribute to enhanced
performance, intestinal microbial balance, and bone quality in broiler chickens
consuming a grower diet that contains corn-DDGS.
PMID- 28419330
TI - Seizure Outcomes in Occipital Lobe and Posterior Quadrant Epilepsy Surgery: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Occipital lobe epilepsy (OLE) is an uncommon but debilitating focal
epilepsy syndrome with seizures often refractory to medical management. While
surgical resection has proven a viable treatment, previous studies examining
postoperative seizure freedom rates are limited by small sample size and patient
heterogeneity, thus exhibiting significant variability in their results.
OBJECTIVE: To review the medical literature on OLE so as to investigate rates and
predictors of both seizure freedom and visual outcomes following surgery.
METHODS: We reviewed manuscripts exploring surgical resection for drug-resistant
OLE published between January 1990 and June 2015 on PubMed. Seizure freedom rates
were analyzed and potential predictors were evaluated with separate meta
analyses. Postoperative visual outcomes were also examined. RESULTS: We
identified 27 case series comprising 584 patients with greater than 1 yr of
follow-up. Postoperative seizure freedom (Engel class I outcome) was observed in
65% of patients, and was significantly predicted by age less than 18 yr (odds
ratio [OR] 1.54, 95% confidence interval [CI] 1.13-2.18), focal lesion on
pathological analysis (OR 2.08, 95% CI 1.58-2.89), and abnormal preoperative
magnetic resonance imaging (OR 3.24, 95% 2.03-6.55). Of these patients, 175 also
had visual outcomes reported with 57% demonstrating some degree of visual decline
following surgery. We did not find any relationship between postoperative visual
and seizure outcomes. CONCLUSION: Surgical resection for OLE is associated with
favorable outcomes with nearly two-thirds of patients achieving postoperative
seizure freedom. However, patients must be counseled regarding the risk of visual
decline following surgery.
PMID- 28419331
TI - An Apoplastic beta-Glucosidase is Essential for the Degradation of Flavonol 3-O
beta-Glucoside-7-O-alpha-Rhamnosides in Arabidopsis.
AB - Flavonol bisglycosides accumulate in plant vegetative tissues in response to
abiotic stress, including simultaneous environmental perturbations (i.e. nitrogen
deficiency and low temperature, NDLT), but disappear with recovery from NDLT.
Previously, we determined that a recombinant Arabidopsis beta-glucosidase (BGLU),
BGLU15, hydrolyzes flavonol 3-O-beta-glucoside-7-O-alpha-rhamnosides and flavonol
3-O-beta-glucosides, forming flavonol 7-O-alpha-rhamnosides and flavonol
aglycones, respectively. In this study, the transient expression of a BGLU15
Cherry fusion protein in onion epidermal cells demonstrated that BGLU15 was
localized to the apoplast. Analysis of BGLU15 T-DNA insertional inactivation
lines (bglu15-1 and bglu15-2) revealed negligible levels of BGLU15 transcripts,
whereas its paralogs BGLU12 and BGLU16 were expressed in wild-type and bglu15
plants. The recombinant BGLU16 did not hydrolyze quercetin 3-O-beta-glucoside-7-O
alpha-rhamnoside or rhamnosylated flavonols, but was active with the synthetic
substrate, p-nitrophenyl-beta-d-glucoside. In addition, shoots of both bglu15
mutants contained negligible flavonol 3-O-beta-glucoside-7-O-alpha-rhamnoside
hydrolase activity, whereas this activity increased by 223% within 2 d of NDLT
recovery in wild-type plants. The levels of flavonol 3-O-beta-glucoside-7-O-alpha
rhamnosides and quercetin 3-O-beta-glucoside were high and relatively unchanged
in shoots of bglu15 mutants during recovery from NDLT, whereas rapid losses were
apparent in wild-type shoots. Moreover, losses of two flavonol 3-O-beta
neohesperidoside-7-O-alpha-rhamnosides and kaempferol 3-O-alpha-rhamnoside-7-O
alpha-rhamnoside were evident during recovery from NDLT, regardless of whether
BGLU15 was present. A spike in a kaempferol 7-O-alpha-rhamnoside occurred with
stress recovery, regardless of germplasm, suggesting a contribution from
hydrolysis of kaempferol 3-O-beta-neohesperidoside-7-O-alpha-rhamnosides and/or
kaempferol 3-O-alpha-rhamnoside-7-O-alpha-rhamnoside by hitherto unknown
mechanisms. Thus, BGLU15 is essential for catabolism of flavonol 3-O-beta
glucoside-7-O-alpha-rhamnosides and flavonol 3-O-beta-glucosides in Arabidopsis.
PMID- 28419332
TI - NEW MODEL FOR MINES AND TRANSPORTATION TUNNELS EXTERNAL DOSE CALCULATION USING
MONTE CARLO SIMULATION.
AB - In this work, a new methodology is developed based on Monte Carlo simulation for
tunnels and mines external dose calculation. Tunnels external dose evaluation
model of a cylindrical shape of finite thickness with an entrance and with or
without exit. A photon transportation model was applied for exposure dose
calculations. A new software based on Monte Carlo solution was designed and
programmed using Delphi programming language. The variation of external dose due
to radioactive nuclei in a mine tunnel and the corresponding experimental data
lies in the range 7.3-19.9%. The variation of specific external dose rate with
position in, tunnel building material density and composition were studied. The
given new model has more flexible for real external dose in any cylindrical
tunnel structure calculations.
PMID- 28419333
TI - Surgical resection for clinical-Stage I radiological pure-solid lung cancer that
met the current high risk criteria.
AB - Objective: We assessed whether surgical resection is acceptable for radiological
invasive non-small cell lung cancer (NSCLC) that met the current high-risk
criteria. Methods: We reviewed 500 clinical-Stage I NSCLCs with a radiological
pure-solid appearance. High-risk criterion was defined as follows: (1)
preoperative FEV1% <= 50% or DLco% <= 50%, (2) age > 75y with 50% < FEV1% < 60%
or 50% < DLco% < 60%, and (3) three or more severe general comorbidities.
Results: The high-risk group comprised 184 (37%) patients. The percentages for
elderly, male, smoker, non-adenocarcinoma histology were significantly higher
than those of the normal-risk group (P < 0.001). Lobectomy was performed in 148
(80%) patients. Overall survival (OS) was significantly worse in the high-risk
group (59.4% vs 73.1%, P = 0.004), however, a multivariate analysis revealed that
high-risk was not associated with poor survival (P = 0.519). Furthermore, there
were no significant differences between the high-risk and normal-risk groups
regarding cancer-specific survival (74.5% vs 79.2%, P = 0.569). Postoperative
morbidity rates were significantly different between the two study arms (45% vs
25%, P < 0.001), however, the 30-day and 90-day mortality rates for the high-risk
group were 1.6% and 3.8%, respectively. In the high-risk patients, the difference
in survival between lobectomy and sublobar resection was not significant (69.4%
vs 78.6%, P = 0.716), and was also proven in the propensity-score matched
patients (82.1% vs 76.0%, P = 0.623). Conclusions: Conventional high-risk
criteria are not always appropriate prognostic variables, and lung cancer
specific survival or short-term mortalities for high-risk patients were fully
acceptable. Surgical therapy including lobectomy should not be readily excluded
from radical local management even when a patient meets the high-risk criteria.
PMID- 28419335
TI - Transfer of the Sick Neonate: What Is Needed?
PMID- 28419334
TI - Effect of a low crude protein diet supplemented with different levels of
threonine on growth performance, carcass traits, blood parameters, and immune
responses of growing broilers.
AB - A study was conducted to evaluate growth performance, carcass traits, blood serum
parameters, and immune responses of Ross 308 male broilers fed diets containing 2
different crude protein (CP) levels (97.5 and 100%) and 4 threonine (Thr) levels
(100, 110, 120, and 130% of Ross recommendations for starter and grower periods).
A completely randomized block design was adopted and main effects (CP and Thr)
were arranged in a 2 * 4 factorial approach. Optimum growth performance was
achieved when broiler requirements for CP and Thr were 100% satisfied. The 110%
Thr inclusion in 97.5% CP diet increased ADG, ADFI, energy intake, and protein
intake (Thr, P < 0.01; quadratic, P = 0.01). The G:F (linear, P = 0.05) and
energy efficiency (linear, P = 0.04) tended to decreased (Thr, P = 0.09) by
increasing Thr supplementation level, whereas protein efficiency tended to
increase (CP, P = 0.06) by reducing CP level. The 110% Thr inclusion in 97.5% CP
diet increased eviscerated carcass weight (CP * Thr, P = 0.03) and carcass yield
(Thr, P = 0.08; quadratic, P = 0.05). The reduction of CP content promoted fat
abdominal deposition (CP, P = 0.05). Incremental Thr raised abdominal fat (Thr, P
= 0.01; linear, P = 0.01). The 97.5% CP diets resulted in higher serum
concentrations of uric acid (CP, P = 0.02), total and high- and low-density
lipoprotein-linked cholesterol (CP, P<= 0.01), and alanine aminotransferase (CP,
P = 0.05) and lower (CP, P = 0.01) concentrations of triglycerides and very low
density lipoproteins compared with the 100% CP diets. However, the Thr inclusion
improved serum lipid profile. Irrespective of CP content, incremental Thr levels
up to 120% increased (Thr, P = 0.01) broiler immune responses against Newcastle
disease virus and sheep red blood cells. In order to reduce dietary CP content,
strategies to increase synthetic amino acid availability, such as the use of
encapsulated amino acids, should be taken into account.
PMID- 28419336
TI - IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1+
cells via the calcineurin-NFATc3-Etv2 pathway.
AB - Ca2+ signals participate in various cellular processes with spatial and temporal
dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated
Ca2+ signals are essential for early development. However, the underlying
mechanisms of IP3R-regulated cell fate decision remain largely unknown. Here we
report that IP3Rs are required for the hematopoietic and cardiac fate divergence
of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced
Flk1+/PDGFRalpha- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor
cell population, and the colony-forming unit activity, but increased cardiac
progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a
key regulator of hematopoiesis, Etv2, was reduced in IP3R-tKO cells, which could
be rescued by the activation of Ca2+ signals and calcineurin or overexpression of
constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific
targeting of Etv2 by NFATc3 via its evolutionarily conserved cis-element in
differentiating ESCs. Importantly, the activation of Ca2+-calcineurin-NFAT
pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an
unrecognized governing role of IP3Rs in hematopoietic and cardiac fate commitment
via IP3Rs-Ca2+-calcineurin-NFATc3-Etv2 pathway.
PMID- 28419338
TI - Primary angiitis of the central nervous system-a territory about to be
discovered.
PMID- 28419337
TI - Targeted Embolization of Aneurysms Associated With Brain Arteriovenous
Malformations at High Risk for Surgical Resection: A Case-Control Study.
AB - BACKGROUND: High-risk components of brain arteriovenous malformations (BAVMs) can
be targeted to reduce the risk of lesion rupture. OBJECTIVE: To evaluate targeted
embolization of aneurysms against other means of treatment with a case-control
analysis; we previously investigated this approach associated with BAVMs.
METHODS: Retrospective analysis of patients with BAVMs was performed, identifying
patients treated with intention to occlude only an aneurysm associated with a
BAVM. For each targeted aneurysm embolization (TAE) patient identified, 4 control
patients were randomly selected, controlling for rupture status, age, and
Spetzler-Martin plus Lawton-Young supplemental score. Analysis was performed to
compare rates of adverse events (hemorrhage, new seizure, and death) between the
2 groups. RESULTS: Thirty-two patients met inclusion criteria, and 128 control
patients were identified, out of 1103 patients treated during the study period.
Thirty-four adverse events occurred (15 ruptures, 15 new seizures, and 11 deaths)
during the follow-up period (mean 1157 d for the TAE cohort and 1036 d for the
non-TAE cohort). Statistically lower associations were noted for the TAE group
for any adverse event (hazard ratio 0.28, P = .037) and the composite outcome of
hemorrhage or new seizure (hazard ratio 0.20, P = .029). CONCLUSION: For BAVMs at
high risk for surgical resection, TAE can be performed safely and effectively.
Patients treated with TAE had better outcomes than matched patients undergoing
other combinations of treatment. TAE can be considered for BAVMs with high
operative risk prior to radiosurgery or when no other treatment options are
available.
PMID- 28419339
TI - Effect of chlorine treatment on inhibition of E. coli serogroup O2 incorporation
into 7-day-old biofilm on polyvinylchloride surface.
AB - Poultry waterlines are constructed using polyvinylchloride (PVC) material on
which bacterial biofilm can easily form. Biofilm can harbor pathogens including
avian pathogenic E. coli (APEC) strains. An in vitro evaluation was performed to
determine if E. coli sero group O2 (avian pathogenic) could attach on a PVC
surface that had pre-formed biofilm and if this phenomenon could be affected when
water was treated with chlorine. Initially, biofilm growth was induced in PVC
test coupons (15.16 cm2) for a 7-day period mimicking the waterline scenario in
the first wk of poultry brooding; and then this biofilm was challenged with E.
coli O2 seeded water in presence/absence of chlorine treatment. After rinsing,
test coupons were sampled for bacterial (APC) and E. coli O2 enumeration at
various occasions post seeding the pathogen and chlorine treatment. Day 7 APC
recovered from coupons was 4.35 log10 cfu/cm2 in trial 1 and 3.66 log10 cfu/cm2
in trial 2. E. coli O2 was not recovered from chlorine treated test coupons (P <
0.05), whereas it was retrieved from untreated coupons (untreated contained > 3
log10 cfu/cm2 in trial 1 and > 2 log10 cfu/cm2 in trial 2). This study suggests
that E. coli O2 can incorporate into pre-formed biofilm on a PVC surface within
24 h if water sanitation is not present, and the attachment time of the pathogen
can prolong in the absence of already formed biofilm.
PMID- 28419341
TI - Letter: Decompressive Surgery for Diabetic Neuropathy: Waiting for
Incontrovertible Proof.
PMID- 28419340
TI - Extremely thick cell walls and low mesophyll conductance: welcome to the world of
ancient living!
AB - Mesophyll conductance is thought to be an important photosynthetic limitation in
gymnosperms, but they currently constitute the most understudied plant group in
regard to the extent to which photosynthesis and intrinsic water use efficiency
are limited by mesophyll conductance. A comprehensive analysis of leaf gas
exchange, photosynthetic limitations, mesophyll conductance (calculated by three
methods previously used for across-species comparisons), and the underlying ultra
anatomical, morphological and chemical traits in 11 gymnosperm species varying in
evolutionary history was performed to gain insight into the evolution of
structural and physiological controls on photosynthesis at the lower return end
of the leaf economics spectrum. Two primitive herbaceous species were included in
order to provide greater evolutionary context. Low mesophyll conductance was the
main limiting factor of photosynthesis in the majority of species. The strongest
sources of limitation were extremely thick mesophyll cell walls, high chloroplast
thickness and variation in chloroplast shape and size, and the low exposed
surface area of chloroplasts per unit leaf area. In gymnosperms, the negative
relationship between net assimilation per mass and leaf mass per area reflected
an increased mesophyll cell wall thickness, whereas the easy-to-measure
integrative trait of leaf mass per area failed to predict the underlying
ultrastructural traits limiting mesophyll conductance.
PMID- 28419342
TI - Future Generations and the Justifiability of Germline Engineering.
AB - The possibility of performing germline modifications on currently living
individuals targets future generations' health and well-being by reducing the
diversity of the human gene pool. This can have two negative repercussions: (1)
reduction of heterozygosity, the latter being associated with a health or
performance advantage; (2) uniformization of the genes involved in reproductive
recombination, which may lead to the health risks involved in asexual
reproduction. I argue that germline interventions aimed at modifying the genomes
of future people cannot be ethically justifiable if there is no possibility of
controlling the intervention either by reversing or altering it, whenever need
demands it. This argument is challenged on six different grounds: safety,
population versus individual focus, spontaneous mutations, exceptionalism, the
intentional pursuit of genetic diversity through germline interventions, and harm
reduction potential.
PMID- 28419343
TI - Utilizing a Modified Care Coordination Measurement Tool to Capture Value for a
Pediatric Outpatient Parenteral and Prolonged Oral Antibiotic Therapy Program.
AB - Background: Outpatient parenteral or prolonged oral antibiotic therapy (OPAT)
programs reduce inpatient healthcare costs by shifting care to outpatient
settings. Care coordination (CC) is a necessary component to successfully
transition patients. Our objective was to assess outcomes of provider time spent
on nonreimbursable CC activities in a pediatric OPAT program. Methods: We used a
qualitative feasibility pilot design and modified the Care Coordination
Measurement Tool. We captured nonreimbursable CC activity and associated
outcome(s) among pediatric patients enrolled in OPAT from March 1 to April 30,
2015 (44 work days) at Doernbecher Children's Hospital. We generated summary
statistics for this institutional review board-waived QI project. Results: There
were 154 nonreimbursable CC encounters conducted by 2 infectious diseases (ID)
providers for 29 patients, ages 17 months-15 years, with complex infections.
Total estimated time spent on CC was 54 hours, equivalent to at least 6 workdays.
Five patients with complex social issues used 37% of total CC time. Of 129 phone
events, 38% involved direct contact with families, pharmacies (13%), primary care
providers (13%), and home health nursing (11%). Care coordination prevented 10
emergency room (ER) visits and 2 readmissions. Care coordination led to 16
additional, not previously scheduled subspecialist and 13 primary care visits.
The OPAT providers billed for 32 clinic visits during the study period.
Conclusions: Nonreimbursable CC work by OPAT providers prevented readmissions and
ER visits and helped facilitate appropriate healthcare use. The value of
pediatric OPAT involvement in patient care would have been underestimated based
on reimbursable ID consultations and clinic visits alone.
PMID- 28419344
TI - A Place to Grow? Host Choice and Larval Performance of Microplitis similis
(Hymenoptera: Braconidae) in the Host Spodoptera litura (Lepidoptera: Noctuidae).
AB - Host selection is a key stage in the lifecycle of parasitoids, and is critical to
both their function in control and to the maintenance of their population. The
solitary endoparasitoid Microplitis similis (Hymenoptera: Braconidae) is a
potential biological control agent of Spodoptera litura (F.) larvae (Lepidoptera:
Noctuidae). In this study, we examined the preference M. similis exhibits for
different instars of the host, host instar effects on parasitoid development, and
the weight gain and food consumption of different instars of parasitized larvae.
In no-choice tests, parasitization rates were highest in second- and early third
instar larvae, and no fourth- or fifth-instar hosts were parasitized. When
provided with a choice of first- to late third-instar host larvae, M. similis
preferred to parasitize early third-instar host larvae (41%) with a selection
coefficient of 0.37. All morphometric features of wasp offspring increased with
increasing age of the host at parasitization. A lower proportion of females
emerged from first-instar larvae than any other instar. Parasitized S. litura
larvae showed a pronounced reduction in food consumption and weight gain.
Microplitis similis may have the potential to significantly suppress population
growth and the damage caused by S. litura.
PMID- 28419345
TI - Dehydration responsive element binding transcription factors and their
applications for the engineering of stress tolerance.
AB - Dehydration responsive element binding (DREB) factors or CRT element binding
factors (CBFs) are members of the AP2/ERF family, which comprises a large number
of stress-responsive regulatory genes. This review traverses almost two decades
of research, from the discovery of DREB/CBF factors to their optimization for
application in plant biotechnology. In this review, we describe (i) the
discovery, classification, structure, and evolution of DREB genes and proteins;
(ii) induction of DREB genes by abiotic stresses and involvement of their
products in stress responses; (iii) protein structure and DNA binding selectivity
of different groups of DREB proteins; (iv) post-transcriptional and post
translational mechanisms of DREB transcription factor (TF) regulation; and (v)
physical and/or functional interaction of DREB TFs with other proteins during
plant stress responses. We also discuss existing issues in applications of DREB
TFs for engineering of enhanced stress tolerance and improved performance under
stress of transgenic crop plants.
PMID- 28419346
TI - Our Shared Vulnerability to Dangerous Pathogens.
AB - The international community vastly underestimates the risk and scale of our
shared vulnerability to fast moving pathogens. Ranging from SARS and novel
influenzas to Ebola and Zika, the world seems to be caught off guard, despite the
regularity of global health threats historically. More importantly, when
governments and international institutions underestimate the threat, they also
underinvest in preparedness. Failure to prepare has deep costs in human lives and
economic productivity. Here, I offer a pathway to preparedness for, and rapid
response to, infectious disease threats: robust and resilient national health
systems; strong institutions capable of leading, particularly the World Health
Organization; and investments in research and development. Overall, the world
needs a strong system of laws and governance, ranging from the International
Health Regulations through to norms of transparency and accountability. To secure
our common future, the world needs sustained investment and leadership. I propose
a 'security dividend', both financial and institutional, to remake the global
health security system.
PMID- 28419347
TI - Evolutionary trade-offs between drought resistance mechanisms across a
precipitation gradient in a seasonally dry tropical oak (Quercus oleoides).
AB - In seasonally dry tropical forest regions, drought avoidance during the dry
season coupled with high assimilation rates in the wet season is hypothesized to
be an advantageous strategy for forest trees in regions with severe and long dry
seasons. In contrast, where dry seasons are milder, drought tolerance coupled
with a conservative resource-use strategy is expected to maximize carbon
assimilation throughout the year. Tests of this hypothesis, particularly at the
intraspecific level, have been seldom conducted. In this study, we tested the
extent to which drought resistance mechanisms and rates of carbon assimilation
have evolved under climates with varying dry season length and severity within
Quercus oleoidesCham. and Schlect., a tropical dry forest species that is widely
distributed in Central America. For this purpose, we conducted a greenhouse
experiment where seedlings originating from five populations that vary in
rainfall patterns were grown under different watering treatments. Our results
revealed that populations from xeric climates with more severe dry seasons
exhibited large mesophyllous leaves (with high specific leaf area, SLA), and leaf
abscission in response to drought, consistent with a drought-avoidance strategy.
In contrast, populations from more mesic climates with less severe dry seasons
had small and thick sclerophyllous leaves with low SLA and reduced water
potential at the turgor loss point (pitlp), consistent with a drought-tolerance
strategy. Mesic populations also showed high plasticity in pitlp in response to
water availability, indicating that osmotic adjustment to drought is an important
component of this strategy. However, populations with mesophyllous leaves did not
have higher maximum carbon assimilation rates under well-watered conditions.
Furthermore, SLA was negatively associated with mass-based photosynthetic rates,
contrary to expectations of the leaf economics spectrum, indicating that drought
resistance strategies are not necessarily tightly coupled with resource-use
strategies. Overall, our study demonstrates the importance of considering
intraspecific variation in analyses of the vulnerability of tropical trees to
climate change.
PMID- 28419348
TI - Litchi Fruit LcNAC1 is a Target of LcMYC2 and Regulator of Fruit Senescence
Through its Interaction with LcWRKY1.
AB - Senescence is a key factor resulting in deterioration of non-climacteric fruit.
NAC transcription factors are important regulators in plant development and
abiotic stress responses, yet little information regarding the role of NACs in
regulating non-climacteric fruit senescence is available. In this study, we
cloned 13 NAC genes from litchi (Litchi chinensis) fruit, and analyzed
subcellular localization and expression profiles of these genes during post
harvest natural and low-temperature-delayed senescence. Of the 13 NAC genes,
expression of LcNAC1 was up-regulated in the pericarp and pulp as senescence
progressed, and was significantly higher in senescence-delayed fruit than that in
naturally senescent fruit. LcNAC1 was induced by exogenous ABA and hydrogen
peroxide. Yeast one-hybrid analysis and transient dual-luciferase reporter assay
showed that LcNAC1 was positively regulated by the LcMYC2 transcription factor.
LcNAC1 activated the expression of LcAOX1a, a gene associated with reactive
oxygen species regulation and energy metabolism, whereas LcWRKY1 repressed
LcAOX1a expression. In addition, LcNAC1 interacted with LcWRKY1 in vitro and in
vivo. These results indicated that LcNAC1 and LcWRKY1 form a complex to regulate
the expression of LcAOX1a antagonistically. Taken together, the results reveal a
hierarchical and co-ordinated regulatory network in senescence of harvested
litchi fruit.
PMID- 28419349
TI - Genomic Signature of Kin Selection in an Ant with Obligately Sterile Workers.
AB - Kin selection is thought to drive the evolution of cooperation and conflict, but
the specific genes and genome-wide patterns shaped by kin selection are unknown.
We identified thousands of genes associated with the sterile ant worker caste,
the archetype of an altruistic phenotype shaped by kin selection, and then used
population and comparative genomic approaches to study patterns of molecular
evolution at these genes. Consistent with population genetic theoretical
predictions, worker-upregulated genes experienced reduced selection compared with
genes upregulated in reproductive castes. Worker-upregulated genes included more
taxonomically restricted genes, indicating that the worker caste has recruited
more novel genes, yet these genes also experienced reduced selection. Our study
identifies a putative genomic signature of kin selection and helps to integrate
emerging sociogenomic data with longstanding social evolution theory.
PMID- 28419350
TI - Epidemiology of Meningitis and Encephalitis in the United States, 2011-2014.
AB - Background: Large epidemiological studies evaluating the etiologies, management
decisions, and outcomes of adults with meningitis or encephalitis in the United
States (US) are lacking. Methods: Adult patients (>=18 years) with meningitis or
encephalitis by International Classification of Diseases, Ninth Revision codes
available in the Premier Healthcare Database during 2011-2014 were analyzed.
Results: A total of 26429 patients with meningitis or encephalitis were
identified. The median age was 43 years; 53% were female. The most common
etiology was enterovirus (13463 [51.6%]), followed by unknown (4944 [21.4%]),
bacterial meningitis (3692 [14.1%]), herpes simplex virus (2184 [8.3%]),
noninfectious (921 [3.5%]), fungal (720 [2.7%]), arboviruses (291 [1.1%]), and
other viruses (214 [0.8%]). Empiric antibiotics, antivirals, and antifungals were
administered in 85.8%, 53.4%, and 7.8%, respectively, and varied by etiologies.
Adjunctive steroids were utilized in 15.9% of all patients and in 39.3% of
patients with pneumococcal meningitis, with an associated decrease in mortality
(6.67% vs 12.5%, P = .0245). The median length of stay was 4 days, with the
longest duration in those with fungal (13), arboviral (10), and bacterial
meningitis (7). Overall inpatient mortality was 2.9% and was higher in those with
bacterial (8.2%), fungal (8.2%), or arboviral (8.9%) disease. Overall readmission
rate at 30 days was 3.2%; patients with arboviral (12.7%), bacterial (6.7%), and
fungal (5.4%) etiologies had higher rates. Conclusions: Viruses are the most
common cause of meningitis and encephalitis in the United States and are treated
with antibiotic therapy in the majority of cases. Adjunctive steroid treatment is
underutilized in pneumococcal meningitis, where it has shown to decrease
mortality.
PMID- 28419351
TI - The effect of diatomaceous earth in live, attenuated infectious bronchitis
vaccine, immune responses, and protection against challenge.
AB - Live virus vaccines are commonly used in poultry production, particularly in
broilers. Massive application and generation of a protective local mucosal and
humoral immunity with no adverse effects is the main goal for this strategy. Live
virus vaccines can be improved by adding adjuvants to boost mucosal innate and
adaptive responses. In a previous study we showed that diatomaceous earth (DE)
can be used as adjuvant in inactivated vaccines. The aim of this study was to
test DE as adjuvant in an Ark-DPI live infectious bronchitis virus (IBV) vaccine
after ocular or spray application. Titrating the virus alone or after addition of
DE showed that DE had no detrimental effect on the vaccine virus. However, adding
DE to the vaccine did not induce higher IgG titers in the serum and IgA titers in
tears. It also did not affect the frequency of CD4+ T cells, CD8+ T cells and
monocytes/macrophages in the blood and the spleen determined by flow cytometry.
In addition, protection generated against IBV homologous challenges, measured by
viral load in tears, respiratory signs and histopathology in tracheas, did not
vary when DE was present in the vaccine formulation. Finally, we confirmed
through our observations that Ark vaccines administered by hatchery spray cabinet
elicit weaker immune responses and protection against an IBV homologous challenge
compared to the same vaccine delivered via ocular route.
PMID- 28419352
TI - Dermatophytes and dermatophytosis in the eastern and southern parts of Africa.
AB - Dermatophytosis is currently a disease of global importance and a public health
burden. It is caused by dermatophytes, which attack and grow on dead animal
keratin. Dermatophytes belong to three genera, namely, Epidermophyton,
Microsporum, and Trichophyton. The predominant clinical forms and causative
agents vary from one region of the world to another. Poor socioeconomic status,
high population densities, and poor sanitary conditions are some of the factors
responsible for the high prevalence of dermatophytosis in many developing
countries, which include countries in southern and eastern Africa, the focus of
this review. To the best of our knowledge, there is currently no review article
on published findings on dermatophytosis in the eastern and southern parts of
Africa. This information will be of interest to the medical and research
community since the world has become a global village. This review covers
published research findings in eastern and southern regions of Africa until this
date. The countries covered in the current review include Kenya, Ethiopia,
Tanzania, South Africa, Mozambique, Madagascar, Malawi, Rwanda, Burundi, Uganda,
Zambia, Zimbabwe, and Botswana. T. violaceum is the most common human etiological
agent in all the countries under review with prevalence ranging from 56.7% to
95%, except for Madagascar (M. langeronii, reclassified as M. audouinii), Uganda
(M. gypseum) and Malawi (M. audouinii). Tinea capitis was the most clinical type,
followed by tinea corporis. Etiological agents of animal dermatophytoses were
variable in the countries where they were reported. Major risk factors for
dermatophytoses are age, climatic, and socioeconomic factors.
PMID- 28419353
TI - The effect of Ramadan fast on the incidence of renal colic emergency department
visits.
AB - Background: Renal colic (RC) is one of the most common reasons for emergency
department (ED) visits. Although RC is associated with high ambient temperature
and with physiological changes that occur during fast, the literature on between
Ramadan and RC incidence is scarce. Aim: To investigate the association of ED
visits with RC during Ramadan fast. Methods: We obtained health data of patients
visited the ED of a large tertiary centre during the years 2004-15, with a
primary diagnosis of RC. To estimate the association of RC and Ramadan, we
utilized bi-weekly RC incidence Poisson models adjusted for ambient temperature
and seasonality in two ethnic groups residing in the region: Muslims and Jews.
Results: We identified 10 435 unique patients with 18 163 ED visits with primary
diagnosis of RC. Although Muslims represent 18.5% of the population in the
region, approximately 25% of the ED visits with RC attributed to this group.
There was a positive and significant association of temperature and ED visits
within all subgroups after adjusting for seasons. Positive association with
Ramadan was observed during the first 2 weeks of fast within Muslims (R.R 1.27,
95% C.I 1.03-1.50) but not within Jewish community (R.R 1.061, 95% C.I 0.855
1.238). Conclusion: Our study demonstrates a significant and positive association
between RC and Ramadan, while controlling to ambient temperature. In view of
these findings, different prevention strategies should be investigated.
PMID- 28419354
TI - Work organization, sleep and metabolic syndrome among long-haul truck drivers.
AB - Background: The work organization of long-haul truck drivers in the USA contains
factors that have been shown to degrade sleep. In combination, these factors
generate elevated cardiometabolic risk by inducing components of the metabolic
syndrome (MetS). However, the prevalence and severity of MetS and the degree to
which such factors differentially influence MetS among these drivers are unknown.
Aims: To determine the prevalence and severity of MetS among US long-haul truck
drivers and to determine the predictive value of demographic, work organization
and sleep variables in MetS diagnosis and severity. Methods: A non-experimental,
descriptive, cross-sectional study, designed to collect survey, anthropometric
and biometric data from US long-haul truck drivers. Descriptive analyses were
performed for demographic, work organization, sleep and MetS measures. Logistic
and linear regression analyses examined potential predictive relationships
between demographic, work organization and sleep variables and MetS diagnosis and
severity. Results: The study population was 262. Nearly 60% of drivers met MetS
diagnosis criteria. Over 80% had a waist circumference >102 cm, 50% had
triglyceride levels of >=150 mg/dl, 66% had an high-density lipoprotein of <40
mg/dl, 28% had a blood pressure of >=135/80 mm Hg and 17% had a fasting glucose
of >=110 mg/dl. Driving experience and work day sleep quality were associated
with MetS prevalence and severity. Conclusions: The prevalence and severity of
MetS among this sample of US long-haul truck drivers were high. Preventive
efforts should focus on experienced drivers and work day sleep quality.
PMID- 28419355
TI - Vegetable Garden as Therapeutic Horticulture for Patients with Chronic Pain.
PMID- 28419356
TI - Arousal-Induced Hypocapnia Does Not Reduce Genioglossus Activity in Obstructive
Sleep Apnea.
AB - Study Objectives: To determine whether arousals that terminate obstructive events
in obstructive sleep apnea (OSA) (1) induce hypocapnia and (2) subsequently
reduce genioglossus muscle activity following the return to sleep. Methods:
Thirty-one untreated patients with OSA slept instrumented with sleep staging
electrodes, nasal mask and pneumotachograph, end-tidal CO2 monitoring, and
intramuscular genioglossus electrodes. End-tidal CO2 was monitored, and
respiratory arousals were assigned an end-arousal CO2 change value (PETCO2 on the
last arousal breath minus each individual's wakefulness PETCO2). This change
value, in conjunction with the normal sleep related increase in PETCO2, was used
to determine whether arousals induced hypocapnia and whether the end-arousal CO2
change was associated with genioglossus muscle activity on the breaths following
the return to sleep. Results: Twenty-four participants provided 1137 usable
arousals. Mean +/- SD end-arousal CO2 change was -0.2 +/- 2.4 mm Hg (below
wakefulness) indicating hypocapnia typically developed during arousal. Following
the return to sleep, genioglossus muscle activity did not fall below prearousal
levels and was elevated for the first two breaths. End-arousal CO2 change and
genioglossus muscle activity were negatively associated such that a 1 mm Hg
decrease in end-arousal CO2 was associated with an ~2% increase in peak and tonic
genioglossus muscle activity on the breaths following the return to sleep.
Conclusions: Arousal-induced hypocapnia did not result in reduced dilator muscle
activity following return to sleep, and thus hypocapnia may not contribute to
further obstructions via this mechanism. Elevated dilator muscle activity
postarousal is likely driven by non-CO2-related stimuli.
PMID- 28419357
TI - Stereoelectroencephalography Using Magnetic Resonance Angiography for Avascular
Trajectory Planning: Technical Report.
AB - BACKGROUND: Stereoelectroencephalography (SEEG) requires high-quality
angiographic studies because avascular trajectory planning is a prerequisite for
the safety of this procedure. Some epilepsy surgery groups have begun to use
computed tomography angiography and magnetic resonance T1-weighted sequence with
contrast enhancement for this purpose. OBJECTIVE: To present the first series of
patients with avascular trajectory planning of SEEG based on magnetic resonance
angiography (MRA). METHODS: Thirty-six SEEG explorations for drug-resistant focal
epilepsy were performed from January 2013 to December 2015. A retrospective
analysis of this consecutive surgical series was then performed. Magnetic
resonance imaging included MRA with a modified contrast-enhanced magnetic
resonance venography (MRV) protocol with a short acquisition delay, which allowed
simultaneous arterial and venous visualization. Our criteria for satisfactory MRA
were the visualization of at least first-order branches of the angular artery,
paracentral and calcarine artery, and third-order tributaries of the superficial
Sylvian vein, vein of Labbe, and vein of Trolard. RESULTS: Thirty-four patients
underwent 36 SEEG explorations with 369 electrodes carrying 4321 contacts.
Contrast-enhanced MRA using the MRV protocol was judged satisfactory for SEEG
planning in all explorations. Postoperative complications were not observed in
our series of 36 SEEG explorations, which included 50 transopercular insular
trajectories. CONCLUSION: MRA using an MRV protocol may be applied for avascular
trajectory planning during SEEG procedures. This technique provides a
simultaneous visualization of cortical arteries and veins without the need for
additional radiation exposure or intra-arterial catheter placement.
PMID- 28419358
TI - Early Cranioplasty is Associated with Greater Neurological Improvement: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Cranioplasty after decompressive craniectomy is a common
neurosurgical procedure, yet the optimal timing of cranioplasty has not been well
established. OBJECTIVE: To investigate whether the timing of cranioplasty is
associated with differences in neurological outcome. METHODS: A systematic
literature review and meta-analysis was performed using MEDLINE, Scopus, and the
Cochrane databases for studies reporting timing and neurological assessment for
cranioplasty after decompressive craniectomy. Pre- and postcranioplasty
neurological assessments for cranioplasty performed within (early) and beyond
(late) 90 d were extracted. The standard mean difference (SMD) was used to
normalize all neurological measures. Available data were pooled to compare pre
cranioplasty, postcranioplasty, and change in neurological status between early
and late cranioplasty cohorts, and in the overall population. RESULTS: Eight
retrospective observational studies were included for a total of 528 patients.
Studies reported various outcome measures (eg, Barthel Index, Karnofsky
Performance Scale, Functional Independence Measure, Glasgow Coma Scale, and
Glasgow Outcome Score). Cranioplasty, regardless of timing, was associated with
significant neurological improvement (SMD .56, P = .01). Comparing early and late
cohorts, there was no difference in precranioplasty neurological baseline;
however, postcranioplasty neurological outcome was significantly improved in the
early cohort (SMD .58, P = .04) and showed greater magnitude of change (SMD 2.90,
P = .02). CONCLUSION: Cranioplasty may improve neurological function, and earlier
cranioplasty may enhance this effect. Future prospective studies evaluating long
term, comprehensive neurological outcomes will be required to establish the true
effect of cranioplasty on neurological outcome.
PMID- 28419359
TI - Improving the Value of Medical Care for Patients with Back Pain.
PMID- 28419361
TI - Effect of electrical stunning frequency and current waveform in poultry welfare
and meat quality.
AB - This study aimed to evaluate the effects of different stunning frequencies and
electrical current waveforms on chicken welfare and meat quality. Two-hundred
thirty-two Cobb broilers, 48 d of age and 2.76 +/- 0.47 live-weight, were
randomly assigned into 4 stunning treatments - 2 frequencies (300 Hz and 650 Hz)
and 2 current waveforms (direct current [DC] and alternating current [AC]).
Broilers were electrically stunned in a water bath in a commercial slaughterhouse
(70 V, 100 mA). The electronarcosis and stunning efficiency were confirmed by
assessment of visual parameters (absence of rhythmic breathing, ocular reflex,
and coordinated wing flapping) and blood parameters (lactate, glucose, creatine
kinase, sodium, and potassium), which were measured after bleeding. The incidence
of traumas and injuries was assessed after plucking. Meat quality analysis was
performed in Pectoralis major (PM), with determinations of pH, breast yield
(PMY), water holding capacity (WHC), water absorption capacity (WAC), thawing
loss (DL), cooking loss (CL), shear force (SF), and instrumental color (a*, b*,
L*, C*, and h). The interaction between waveform and frequency was significant (P
< 0.05) only for lactate, sodium, and lightness (L*). Lactate and sodium levels
decreased at 300 Hz-DC. Meat lightness increased at 300 Hz-DC. The individual
effect of frequency was significant for glucose, creatine kinase, potassium, WHC,
PMY, b*, C*, and h. Regarding waveform, AC decreased plasma glucose and DC
decreased creatine kinase and WAC. In general, stunning frequency exerts greater
influence than waveform on the welfare and meat quality parameters of broilers.
The use of frequency at 650 Hz proved to render animals efficiently unconscious
and to promote greater meat quality.
PMID- 28419360
TI - P4HA1 mutations cause a unique congenital disorder of connective tissue involving
tendon, bone, muscle and the eye.
AB - Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and
stabilization of the triple helical domain of collagens. P4HA1 encodes the
catalytic alpha(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report
human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of
connective tissue, manifesting as early-onset joint hypermobility, joint
contractures, muscle weakness and bone dysplasia as well as high myopia, with
evidence of clinical improvement of motor function over time in the surviving
patient. Similar to P4ha1 null mice, which die prenatally, the muscle tissue from
P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle
basement membrane. Patients were compound heterozygous for frameshift and splice
site mutations leading to reduced, but not absent, P4HA1 protein level and C-P4H
activity in dermal fibroblasts compared to age-matched control samples.
Differential scanning calorimetry revealed reduced thermal stability of collagen
in patient-derived dermal fibroblasts versus age-matched control samples.
Mutations affecting the family of C-P4Hs, and in particular C-P4H-I, should be
considered in patients presenting with congenital connective tissue/myopathy
overlap disorders with joint hypermobility, contractures, mild skeletal dysplasia
and high myopia.
PMID- 28419362
TI - Obesity as a Presentation of Munchausen Syndrome by Proxy.
AB - Objective: To describe a case of an obese child whose weight gain was related to
the Munchausen Syndrome by proxy (MSP). Methods: This is a case report including
information regarding the child's clinical history and the mother's behavior. The
common features of the syndrome are confronted with the description of the case,
seeking to demonstrate the similarities. Results: The description ratifies the
diagnosis based on the signs and symptoms presented by the child (<5 years old,
frequent contacts with health system, symptoms witnessed only by the mother,
confusing findings, not helped by treatments, emotionally distant father) and the
attitude of the mother (concerned, interested in procedures, comfortable in the
medical setting, higher medical knowledge, hostile when thwarted). Conclusion:
The case presented points to a new etiology, the MSP, to be considered within the
set of factors currently known to cause and maintain obesity in childhood.
PMID- 28419363
TI - Applying 'drought' to potted plants by maintaining suboptimal soil moisture
improves plant water relations.
AB - Pot-based phenotyping of drought response sometimes maintains suboptimal soil
water content by applying high-frequency deficit irrigation (HFDI). We examined
the effect of this treatment on water and abscisic acid (ABA) relations of two
species (Helianthus annuus and Populus nigra). Suboptimal soil water content was
maintained by frequent irrigation, and compared with the effects of withholding
water and with adequate irrigation. At the same average whole-pot soil moisture,
frequent irrigation resulted in larger soil water content gradients, lower root
and xylem ABA concentrations ([X-ABA]), along with higher transpiration rates or
stomatal conductance, compared with plants from which water was withheld. [X-ABA]
was not uniquely related to transpiration rate or stomatal conductance, as
frequently irrigated plants showed partial stomatal closure compared with well
watered controls, without differing in [X-ABA] and, in H. annuus, [ABA]leaf. In
two P. nigra genotypes differing in leaf area, the ratio between leaf area and
root weight in the upper soil layer influenced the soil water content of this
layer. Maintaining suboptimal soil water content alters water relations, which
might become dependent on root distribution and leaf area, which influences soil
water content gradients. Thus genotypic variation in 'drought tolerance' derived
from phenotyping platforms must be carefully interpreted.
PMID- 28419364
TI - Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage
fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients.
AB - We clarified the performance of a cryptococcal glucuronoxylomannan (GXM) antigen
test using bronchoalveolar lavage fluid (BALF) samples, in an HIV-negative
Japanese population. Between March 2008 and December 2014, we examined
cryptococcal GXM antigens in both serum and BALF specimens from 429 cases at
Nagasaki University hospital. The diagnoses, underlying diseases, chest computed
tomography findings, and cryptococcal GXM antigen test results were
retrospectively investigated. Twenty-three patients were confirmed to have
pulmonary cryptococcosis, another six were clinically diagnosed with
cryptococcosis because they were seropositive for the GXM antigen, and five
possible cryptococcosis cases had BALF samples that were positive for the GXM
antigen and serum samples that were negative. The test's sensitivities for
detecting cryptococcal GXM antigens in serum and BALF samples, for confirmed
cases, were 73.9% and 82.6%, respectively, and their respective specificities
were 98.5% and 97.8%. Three of the five putative patients with cryptococcosis
were treated with antifungal agents; the pulmonary lesions decreased in size in
all treated patients. Both the BALF and serum GXM antigen titers showed positive
correlations with the lesion sizes; however, the serum antigen titers showed a
higher correlation (r = 0.490, P = .0033) than did the BALF titres (r = 0.312, P
= .0724). The rate of GXM-positive BALF samples was higher than the rate for
serum samples, especially for patients with pulmonary lesion diameters <=25 mm.
Testing for the presence of the cryptococcal GXM antigen in BALF specimens might
contribute to the early diagnosis of pulmonary cryptococcosis.
PMID- 28419365
TI - Redefining health for the 21st century: investing in well-being-the proper
meaning of 'health-care'.
PMID- 28419366
TI - Effect of methionine supplementation in chicken feed on the quality and shelf
life of fresh poultry meat.
AB - The aim of this study was to investigate the influence of different methionine
sources and concentrations on the quality and spoilage process of broiler meat.
The trial was comprised of 7 treatment groups: one basal group (suboptimal in
Methionine+Cysteine; i.e., 0.89, 0.74, 0.69% in DM SID Met+Cys in starter,
grower, and finisher diets, respectively) and 3 doses (0.10, 0.25, and 0.40%) of
either DL-Methionine (DLM) or DL-2-hydroxy-4-methylthio butanoic acid (DL-HMTBA)
on an equimolar basis of the DLM-supplemented groups. The broilers were fed the
diets for 35 d, then slaughtered and processed. The filets were aerobically
packed and stored under temperature controlled conditions at 4 degrees C. Meat
quality investigations were comprised of microbial investigations (total viable
count and Pseudomonas spp.), pH and drip loss measurements of the filets. The
shelf life of the meat samples was determined based on sensory parameters. After
slaughtering, all supplemented meat samples showed a high quality, whereby no
differences between the 2 methionine sources could be detected for the microbial
load, pH, and drip loss. In comparison to the control group, the supplemented
samples showed a higher sensory quality, characterized by a fresh smell and fresh
red color. Methionine supplementation had a significant influence on meat quality
parameters during storage. The microbial load, pH and drip loss of the chicken
filets were positively correlated to the methionine concentration. Additionally,
the microbial load at the end of storage was positively correlated to pH and drip
loss values. Nevertheless, the microbial parameters were in a normal range and
the positive correlation to methionine concentration did not affect the sensory
shelf life. The mean sensory shelf life of the broiler filets varied between 7 to
9 d. During storage, no difference in the development of sensory parameters was
observed between the supplemented groups, while the spoilage process of the basal
group occurred slightly faster. In conclusion, methionine concentration, but not
methionine source, effected meat quality parameters in breast muscles of
broilers.
PMID- 28419367
TI - Evaluating the Impact of LTA4H Genotype and Immune Status on Survival From
Tuberculous Meningitis.
PMID- 28419368
TI - Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral
Inflammation and Survival From Tuberculous Meningitis.
AB - Background: Tuberculous meningitis (TBM) is the most devastating form of
tuberculosis, yet very little is known about the pathophysiology. We hypothesized
that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which
determines inflammatory eicosanoid expression, influences intracerebral
inflammation, and predicts survival from TBM. Methods: We characterized the
pretreatment clinical and intracerebral inflammatory phenotype and 9-month
survival of 764 adults with TBM. All were genotyped for single-nucleotide
polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal
fluid (CSF) leukocyte and cytokine concentrations. Results: LTA4H genotype
predicted survival of human immunodeficiency virus (HIV)-uninfected patients,
with TT-genotype patients significantly more likely to survive TBM than CC
genotype patients, according to Cox regression analysis (univariate P = .040 and
multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF
proinflammatory cytokine concentrations, with intermediate and lower
concentrations in those with CT and CC genotypes. Increased CSF cytokine
concentrations correlated with more-severe disease, but patients with low CSF
leukocytes and cytokine concentrations were more likely to die from TBM. HIV
infection independently predicted death due to TBM (hazard ratio, 3.94; 95%
confidence interval, 2.79-5.56) and was associated with globally increased CSF
cytokine concentrations, independent of LTA4H genotype. Conclusions: LTA4H
genotype and HIV infection influence pretreatment inflammatory phenotype and
survival from TBM. LTA4H genotype may predict adjunctive corticosteroid
responsiveness in HIV-uninfected individuals.
PMID- 28419369
TI - Laboratory x-ray micro-computed tomography: a user guideline for biological
samples.
AB - Laboratory x-ray micro-computed tomography (micro-CT) is a fast-growing method in
scientific research applications that allows for non-destructive imaging of
morphological structures. This paper provides an easily operated "how to" guide
for new potential users and describes the various steps required for successful
planning of research projects that involve micro-CT. Background information on
micro-CT is provided, followed by relevant setup, scanning, reconstructing, and
visualization methods and considerations. Throughout the guide, a Jackson's
chameleon specimen, which was scanned at different settings, is used as an
interactive example. The ultimate aim of this paper is make new users familiar
with the concepts and applications of micro-CT in an attempt to promote its use
in future scientific studies.
PMID- 28419370
TI - Distinguishing industrial meat from that of indigenous chickens with molecular
markers.
AB - The aim of investigation was to evaluate a traceability system to detect
industrial chicken meat among indigenous products, considering issues that could
affect assignment accuracy. The dataset included 2 Italian indigenous meat
breeds, namely Bionda Piemontese (2 ecotypes) and Bianca di Saluzzo, one broiler
line, and 3 layer lines. Assignment tests were performed using a standard panel
of 28 microsatellite loci. To evaluate effects of inbreeding and substructure on
assignment accuracy, a simulated dataset was prepared. Broilers and layers belong
to homogeneous populations and never enter the clusters of indigenous breeds.
Ambiguity or misallocation are expected between the Bionda ecotypes and between
the 2 indigenous breeds, but it is unlikely that niche products provided by
Bionda and Bianca will compete with one another. Non-random mating reduces
accuracy, but only populations having weak genetic differentiation are involved,
namely those that are less interesting to discriminate. The dataset can be used
as a reference population to distinguish commercial meat from indigenous meat
with great accuracy. Misallocations increase as number of loci decreases, but
only within or between the indigenous breeds. A subpanel of the most resolving 14
loci keeps sufficient informative content to provide accuracy and to correctly
allocate additional test samples within the reference population. This analytical
tool is economically sustainable as a method to detect fraud or mislabeling.
Adoption of a monitoring system should increase the value of typical products
because the additional burden of molecular analyses would improve commercial
grade and perception of quality.
PMID- 28419371
TI - Sleep: A Window Into Autonomic Control in Children Born Preterm and Growth
Restricted.
AB - Study Objectives: Preterm birth and fetal growth restriction (FGR) are both
associated with risk of hypertension in adulthood. Mechanisms leading to this
pathology are unclear. In children aged 5-12 years, who were born preterm and
FGR, we used sleep as a tool to assess autonomic control with assessment of
cardiovascular structure and function. Methods: Eighteen children born preterm
and FGR, 15 children born preterm with appropriate birth weights for gestational
age (AGA), and 20 AGA term-born children were studied. Children underwent
overnight polysomnography with the addition of continuous noninvasive blood
pressure (FinometerTM). Spectral measures of heart rate variability (HRV), blood
pressure variability (BPV), and baroreflex sensitivity were assessed and
overnight urinary catecholamine levels measured. Echocardiographic studies
(Vivid7, GE Healthcare) were performed and vascular compliance assessed (Miller
InstrumentsTM). Statistical comparisons were adjusted for age and body size.
Results: Compared to term children, preterm AGA children had increased high
frequency HRV (p < .05) and BPV (p < .05) during sleep, reflecting increased
parasympathetic activation and blood pressure changes related to respiration.
Preterm FGR children had smaller left ventricular lengths, ascending aorta, and
left ventricular outflow tract diameter (p < .05 for all) and vascular compliance
was positively correlated with gestational age (r2 = 0.93, p < .05). Conclusions:
FGR combined with preterm birth did not alter autonomic control but altered heart
structure in children. In contrast, preterm birth alone altered autonomic control
but had no change in heart structure. These changes in children born preterm and
FGR may contribute, in part, to increased risk of cardiovascular disease later in
life but by different mechanisms.
PMID- 28419372
TI - Nutrient and fiber utilization responses of supplemental xylanase in broiler
chickens fed wheat based diets are independent of the adaptation period to test
diets.
AB - The effects of adaptation (AD) to xylanase-supplemented diets on nutrient and
fiber utilization in 21-d-old broilers were investigated. Six treatments,
arranged in two levels of AD (starting at d 0 or d 14 of age) and three levels of
xylanase (0 or 2,500 or 5,000 xylanase units/kg feed) were used. All diets had
500 phytase U/kg and 0.3% TiO2 as indigestible marker. A total of 384 d old male
broiler (Ross 308) chicks were divided into two groups. The first group was
assigned on weight basis to 24 cages (8 chicks per cage) and randomly allocated
to the diets from d 0. Birds in the second group were reared on a commercial
starter diet in the same room for 13 d. On d 14, the birds were individually
weighed, assigned on weight basis to 24 cages (8 chicks per cage), and randomly
allocated to the diets. Birds had free access to experimental diets and water.
Excreta samples were collected from d 18 to 21. On d 21, all birds were
euthanized to access ileal digesta. There was no interaction (P > 0.05) between
AD and xylanase on the apparent ileal digestibility (AID) and apparent retention
(AR) of components. The main effect of AD was such that the birds exposed to
diets for 7 d (d 14 to 21) had higher (P < 0.01) AID of energy than those exposed
for 21 d (d 0 to 21). In contrast, birds exposed to diets for 21 d had higher (P
< 0.05) AMEn and AR of neutral detergent fiber. Xylanase improvements (P < 0.01)
in the AID of energy and AMEn were dose dependent and coincided with linear
improvements (P < 0.05) in the AID of nitrogen, fat, and starch. In conclusion,
xylanase improvements on retention of fiber and nutrients were independent of AD
(7 or 21 d) suggesting that the xylanase effects are not transitional. Greater
retention of fiber with longer AD is suggestive of possible microbial adaptation.
PMID- 28419373
TI - Trends in the Prevalence of Morbid Obesity among Children and Adolescents in
Shandong, China, 1995-2014.
AB - Background: Childhood obesity has increased dramatically during the past decades;
however, data on the prevalence of morbid obesity is limited. The present study
examined the prevalent trends in morbid obesity among children and adolescents
during the past 19 years (1995-2014) in Shandong, China. Methods: Data for this
study were obtained from five cross-sectional surveys (1995, 2000, 2005, 2010 and
2014) of schoolchildren in Shandong Province, China. A total of 41 500 students
aged 7-18 years were included in this study. Body mass index cutoffs recommended
by the International Obesity Task Force were used to define morbid obesity.
Results: The prevalence of morbid obesity was increasing continuously during the
past 19 years (1995-2014), from 0.25% for boys and 0.11% for girls in 1995 to
2.73% for boys and 1.29% for girls in 2014. Boys had higher prevalence of morbid
obesity than girls (p<0.01). Regional socioeconomic status (SES) inequalities in
morbid obesity were observed; children and adolescents from high SES district had
a rapid increase in the prevalence of morbid obesity than their counterparts from
moderate SES and low SES districts in the past 19 years. Conclusion: Although the
current prevalence of morbid obesity was at a relatively low level, a continuous
increasing trend was observed between 1995 and 2014. We should not relax our
vigilance, and policymakers and experts should pay more attention to the
monitoring and prevention of morbid obesity among children and adolescents in the
future decades.
PMID- 28419374
TI - Patient Radiation Doses in Therapeutic Endoscopic Retrograde
Cholangiopancreatography in Patras and the Key Role of the Operator.
AB - The patient radiation doses, in conjunction with the operator experience, in
therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures,
performed in our hospital, were obtained. Ninety-six patients participated in the
study and were divided into 3 groups, based on the operator experience. The
dosemetric indices, fluoroscopy time (FT), cumulative dose (Ka,r) and air kerma
area product (PKA), were collected. For the total and weight banding group the
third quartile values of the distribution of FT, Ka,r and PKA were 2.90 and 2.92
min, 6.89 and 6.93 mGy and 1.84 and 1.85 Gycm2, respectively, and were
comparative or significantly lower than the corresponding values previously
reported. Taking as a criterion the operator, the differences in the patient
radiation doses were statistically significant, with the highest dose recorded
for the operator of the lowest experience degree. The values obtained could
contribute in establishing local and national diagnostic reference levels and in
optimising ERCP procedure.
PMID- 28419376
TI - Latent TB infection and pulmonary TB disease among patients with diabetes
mellitus in Bandung, Indonesia.
AB - Background: Screening and treatment of latent TB infection (LTBI) and TB disease
could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the
prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic
setting. Methods: Patients with DM attending a hospital and community centres in
Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay
(IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from
a parallel study were age- and sex-matched to patients with DM to compare LTBI
and TB disease prevalence. Results: Of 682 patients with DM screened, 651 (95.5%)
were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9%
(206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA
positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95%
CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI
1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded
households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45). Conclusions:
LTBI prevalence in patients with DM was lower than in household contacts, but
patients with DM were more likely to have TB disease. Further studies should
explore possible benefits of LTBI screening and preventive therapy in patients
with DM in TB-endemic settings.
PMID- 28419375
TI - Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies
Changes in Expression of Genes Between Sleep and Wake.
AB - Study objective: To assess differences in gene expression in cholinergic basal
forebrain cells between sleeping and sleep-deprived mice sacrificed at the same
time of day. Methods: Tg(ChAT-eGFP)86Gsat mice expressing enhanced green
fluorescent protein (eGFP) under control of the choline acetyltransferase (Chat)
promoter were utilized to guide laser capture of cholinergic cells in basal
forebrain. Messenger RNA expression levels in these cells were profiled using
microarrays. Gene expression in eGFP(+) neurons was compared (1) to that in eGFP(
) neurons and to adjacent white matter, (2) between 7:00 am (lights on) and 7:00
pm (lights off), (3) between sleep-deprived and sleeping animals at 0, 3, 6, and
9 hours from lights on. Results: There was a marked enrichment of ChAT and other
markers of cholinergic neurons in eGFP(+) cells. Comparison of gene expression in
these eGFP(+) neurons between 7:00 am and 7:00 pm revealed expected differences
in the expression of clock genes (Arntl2, Per1, Per2, Dbp, Nr1d1) as well as
mGluR3. Comparison of expression between spontaneous sleep and sleep-deprived
groups sacrificed at the same time of day revealed a number of transcripts (n =
55) that had higher expression in sleep deprivation compared to sleep. Genes
upregulated in sleep deprivation predominantly were from the protein folding
pathway (25 transcripts, including chaperones). Among 42 transcripts upregulated
in sleep was the cold-inducible RNA-binding protein. Conclusions: Cholinergic
cell signatures were characterized. Whether the identified genes are changing as
a consequence of differences in behavioral state or as part of the molecular
regulatory mechanism remains to be determined.
PMID- 28419377
TI - Gene-Tree Reconciliation with MUL-Trees to Resolve Polyploidy Events.
AB - Polyploidy can have a huge impact on the evolution of species, and it is a common
occurrence, especially in plants. The two types of polyploids-autopolyploids and
allopolyploids-differ in the level of divergence between the genes that are
brought together in the new polyploid lineage. Because allopolyploids are formed
via hybridization, the homoeologous copies of genes within them are at least as
divergent as orthologs in the parental species that came together to form them.
This means that common methods for estimating the parental lineages of
allopolyploidy events are not accurate, and can lead to incorrect inferences
about the number of gene duplications and losses. Here, we have adapted an
algorithm for topology-based gene-tree reconciliation to work with multi-labeled
trees (MUL-trees). By definition, MUL-trees have some tips with identical labels,
which makes them a natural representation of the genomes of polyploids. Using
this new reconciliation algorithm we can: accurately place allopolyploidy events
on a phylogeny, identify the parental lineages that hybridized to form
allopolyploids, distinguish between allo-, auto-, and (in most cases) no
polyploidy, and correctly count the number of duplications and losses in a set of
gene trees. We validate our method using gene trees simulated with and without
polyploidy, and revisit the history of polyploidy in data from the clades
including both baker's yeast and bread wheat. Our re-analysis of the yeast data
confirms the allopolyploid origin and parental lineages previously identified for
this group. The method presented here should find wide use in the growing number
of genomes from species with a history of polyploidy. [Polyploidy;
reconciliation; whole-genome duplication.].
PMID- 28419378
TI - Arsenic-induced testicular toxicity in Gallus gallus: Expressions of inflammatory
cytokines and heat shock proteins.
AB - The aim of the study is to investigate the effects of sub-chronic poisoning with
arsenic on the testes of chickens treated. Seventy-two 1-day-old chickens were
randomly divided into 4 groups and provided food with different doses arsenic.
The histological changes were examined. The mRNA levels of inflammatory factors,
including transcription factor nuclear factor-kappaB (NF-kappaB), tumor necrosis
factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), cyclooxygenase
2 (COX-2), prostaglandin E synthase (PTGEs), and heat shock proteins (Hsps),
including Hsp70, Hsp90, Hsp60, Hsp40, and Hsp27 were assessed by quantitative
real-time PCR in the testes of chickens. The protein expressions of iNOS, Hsp60,
and Hsp70 were detected by western blot. Increased mRNA and protein levels of
inflammatory factors and Hsps with testicular damage showed that arsenic-induced
testicular toxicity includes inflammatory and heat shock response in chickens,
and that increased Hsps levels may play a protective role in inflammation damage
induced by arsenic on the testes of chickens.
PMID- 28419379
TI - Central Sensitization Is Modulated Following Trigger Point Anesthetization in
Patients with Chronic Pain from Whiplash Trauma. A Double-Blind, Placebo
Controlled, Crossover Study.
AB - Objective: Central sensitization (CS) with low peripheral pain thresholds (PPTs)
is a common finding among patients with chronic pain after whiplash (CPWI). While
it has been proposed that myofascial myofascial trigger points (MTrPs) may act as
modulators of central sensitization, previously reported findings are conflicting
and inconclusive. The present study was designed to investigate immediate
responsiveness of CS to alterations in nociceptive input. Design: Controlled,
double-blind, cross-over. Subjects: Thirty-one patients with chronic pain
(trapezius myalgia) and CS after whiplash. Methods: Participants were referred by
randomization to group A for injection of a single peripheral pain generator
(MTrP or other discrete tender point) with local anesthetic or to group B for
sham injection and cross-over. Documentation of PPT (Algometer), maximum jaw
opening (caliper), and grip strength (Vigorimeter), as well as subjective overall
pain (visual analog scale [VAS]), was made before and after each intervention.
Results: Statistical analysis of data (Student's t test, analysis of variance)
confirmed that peripheral pain thresholds were significantly higher and maximum
jaw opening significantly greater after anesthetizing a focal pain generator in
the trapezius, but not after a sham injection. In contrast with the objective
variables, subjective generalized pain improved (VAS) after not only an injection
of local anesthetic, but also, and to a similar extent, after a sham injection.
Conclusions: CS, as expressed by lowered PPT, is a rapidly adjusting
physiological response to nociceptive stimuli in some patients with chronic pain
after whiplash. PPT are likely modulated by myofascial tender points in selected
patients with CS. With reference to the present findings, surgical ablation of
MTrPs is discussed as a potential treatment modality for CS.
PMID- 28419380
TI - beta-Carboxysome bioinformatics: identification and evolution of new bacterial
microcompartment protein gene classes and core locus constraints.
AB - Carboxysomes are bacterial microcompartments (BMCs) that enhance CO2 fixation in
all cyanobacteria. Structurally, carboxysome shell proteins are classified
according to the type of oligomer formed: hexameric (BMC-H), trimeric (BMC-T) and
pentameric (BMC-P) proteins. To understand the forces driving the evolution of
the carboxysome shell, we conducted a bioinformatic study of genes encoding beta
carboxysome shell proteins, taking advantage of the recent large increase in
sequenced cyanobacterial genomes. In addition to the four well-established BMC-H
(CcmK1-4) classes, our analysis reveals two new CcmK classes, which we name CcmK5
and CcmK6. CcmK5 is phylogenetically closest to CcmK3 and CcmK4, and the ccmK5
gene is found only in genomes lacking ccmK3 and ccmk4 genes. ccmK6 is found
predominantly in heterocyst-forming cyanobacteria. The gene encoding the BMC-T
homolog CcmO is associated with the main carboxysome locus (MCL) in only 60% of
all species. We find five evolutionary origins of separation of ccmO from the
MCL. Transcriptome analysis demonstrates that satellite ccmO genes, in contrast
to MCL-associated ccmO genes, are never co-regulated with other MCL genes. The
dispersal of carboxysome shell genes across the genome allows for distinct
regulation of their expression, perhaps in response to changes in environmental
conditions.
PMID- 28419382
TI - Assessing Flight Potential of the Invasive Asian Longhorned Beetle (Coleoptera:
Cerambycidae) With Computerized Flight Mills.
AB - The Asian longhorned beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera:
Cerambycidae: Lamiinae), is an invasive woodborer that poses a serious threat to
urban and natural landscapes. In North America, this beetle is a quarantine pest,
and populations are subject to eradication efforts that consist of the
identification, removal, and destruction of infested host material, and removal
or prophylactic treatment of high-risk host plant species. To enhance Asian
longhorned beetle eradication protocols in landscapes with extensive host
availability, we assessed the dispersal potential of male and female adults of
varying age, mating, and nutritional status using computerized flight mills. In
total, 162 individuals were tethered to computerized flight mills for a 24-h
trial period to collect information on total distance flown, flight times and
velocities, and number and duration of flight bouts. Adult Asian longhorned
beetles (in all treatments) flew an average of 2,272 m within a 24-h period, but
are capable of flying up to 13,667 m (8.5 miles). Nutrition and age had the
greatest impacts on flight, with Asian longhorned beetle adults >5 d of age that
had fed having greater overall flight performance than any other group. However,
mating status, sex, and body size (pre-flight weight and elytron length) had a
minimal effect on flight performance. This information will be useful for
refining quarantine zones surrounding areas of infestation, and for providing
greater specificity as to the risk the Asian longhorned beetle poses within
invaded regions.
PMID- 28419381
TI - Enhancing faba bean (Vicia faba L.) genome resources.
AB - Grain legume improvement is currently impeded by a lack of genomic resources. The
paucity of genome information for faba bean can be attributed to the intrinsic
difficulties of assembling/annotating its giant (~13 Gb) genome. In order to
address this challenge, RNA-sequencing analysis was performed on faba bean (cv.
Wizard) leaves. Read alignment to the faba bean reference transcriptome
identified 16 300 high quality unigenes. In addition, Illumina paired-end
sequencing was used to establish a baseline for genomic information assembly.
Genomic reads were assembled de novo into contigs with a size range of 50-5000
bp. Over 85% of sequences did not align to known genes, of which ~10% could be
aligned to known repetitive genetic elements. Over 26 000 of the reference
transcriptome unigenes could be aligned to DNA-sequencing (DNA-seq) reads with
high confidence. Moreover, this comparison identified 56 668 potential splice
points in all identified unigenes. Sequence length data were extended at 461
putative loci through alignment of DNA-seq contigs to full-length, publicly
available linkage marker sequences. Reads also yielded coverages of 3466* and
650* for the chloroplast and mitochondrial genomes, respectively. Inter- and
intraspecies organelle genome comparisons established core legume organelle gene
sets, and revealed polymorphic regions of faba bean organelle genomes.
PMID- 28419383
TI - Cell Death Biomarkers and Obstructive Sleep Apnea: Implications in the Acute
Coronary Syndrome.
AB - Study Objectives: Nucleosomes and cell-free double-stranded DNA (dsDNA) have been
suggested as promising biomarkers in cell death-related diseases, such as acute
coronary syndrome (ACS). Currently, the impact of obstructive sleep apnea (OSA)
in patients with ACS is unclear. Our aim was to evaluate the relationship between
OSA, dsDNA, and nucleosomes and to assess their potential implication in the
development of ACS. Methods: Up to 549 patients were included in the study and
divided into four groups (145 ACS; 290 ACS + OSA; 62 OSA; 52 controls). All
patients underwent a sleep study, and serum concentrations of dsDNA and
nucleosomes were measured. Results: Nucleosome and dsDNA levels were higher in
patients with OSA than in controls (nucleosomes: 1.47 +/- 0.88 arbitary units
[AU] vs. 1.00 +/- 0.33 AU; p < .001, dsDNA: 315.6 +/- 78.0 ng/mL vs. 282.6 +/-
55.4 ng/mL; p = .007). In addition, both biomarker levels were higher in patients
with ACS than in non-ACS, independently of the presence of OSA. Conclusions: Both
nucleosomes and dsDNA are increased in patients with OSA and might be related
with the high cardiovascular risk seen in these patients. The extensive cell
lysis during a myocardial infarction seems to be the major contributor to the
high biomarker levels, and OSA does not seem to be implicated in such elevation
when this acute event occurs. Clinical trial registration: NCT01335087
(clinicaltrials.gov).
PMID- 28419384
TI - Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or
Overdose: Comparison of Commercially Insured and Veterans Health Affairs
Populations.
AB - Objective: To characterize the risk factors associated with overdose or serious
opioid-induced respiratory depression (OIRD) among medical users of prescription
opioids in a commercially insured population (CIP) and to compare risk factor
profiles between the CIP and Veterans Health Administration (VHA) population.
Subjects and Methods: Analysis of data from 18,365,497 patients in the IMS
PharMetrics Plus health plan claims database (CIP) who were dispensed a
prescription opioid in 2009 to 2013. Baseline factors associated with an event of
serious OIRD among 7,234 cases and 28,932 controls were identified using
multivariable logistic regression. The CIP risk factor profile was compared with
that from a corresponding logistic regression among 817 VHA cases and 8,170
controls in 2010 to 2012. Results: The strongest associations with serious OIRD
in CIP were diagnosed substance use disorder (odds ratio [OR] = 10.20, 95%
confidence interval [CI] = 9.06-11.40) and depression (OR = 3.12, 95% CI = 2.84
3.42). Other strongly associated factors included other mental health disorders;
impaired liver, renal, vascular, and pulmonary function; prescribed fentanyl,
methadone, and morphine; higher daily opioid doses; and concurrent psychoactive
medications. These risk factors, except depression, vascular disease, and
specific opioids, largely aligned with VHA despite CIP being substantially
younger, including more females and less chronic disease, and having greater
prescribing prevalence of higher daily opioid doses, specific opioids, and most
selected nonopioids. Conclusions: Risk factor profiles for serious OIRD among US
medical users of prescription opioids with private or public health insurance
were largely concordant despite substantial differences between the populations
in demographics, clinical conditions, health care delivery systems, and clinical
practices.
PMID- 28419385
TI - Development and Feasibility of a Group-Based Therapeutic Yoga Program for Women
with Chronic Pelvic Pain.
AB - Objective: To develop a group-based therapeutic yoga program for women with
chronic pelvic pain (CPP) and explore the effects of this program on pain
severity, sexual function, and well-being. Methods: A yoga therapy program for
CPP was developed by a multidisciplinary panel of clinicians, researchers, and
yoga consultants. Women reporting moderate to severe pelvic pain for at least six
months were recruited into a single-arm trial. Participants attended twice weekly
group classes focusing on Iyengar-based yoga techniques and were instructed to
practice yoga at home an hour a week for six weeks. Participants self-rated the
severity of their pelvic pain using daily logs. The impact of participants' pain
on everyday activities, emotional well-being, and sexual function was assessed
using an Impact of Pelvic Pain (IPP) questionnaire. Sexual function was further
assessed using the Sexual Health Outcomes in Women Questionnaire (SHOW-Q).
Results: Among the 16 participants (age range = 31-64 years), average ratings of
the severity of pain "at its worst," "at its best," and "on average" decreased by
29%, 32%, and 34%, respectively, from start to six weeks (P < 0.05 for all).
Women demonstrated improvements in scores on IPP subscales for daily activities
(1.8 +/- 0.7 to 0.9 +/- 0.7, P < 0.001), emotional well-being (1.7 +/- 0.9 to 0.9
+/- 0.7, P = 0.005), and sexual function (1.9 +/- 1.1 to 1.0 +/- 0.9, P = 0.04).
Scores on the SHOW-Q "pelvic problem interference" scale also improved over six
weeks (53 +/- 23 to 27 +/- 23, P = 0.002). Conclusions: Findings provide
preliminary evidence of the feasibility of teaching women with CPP to practice
yoga to self-manage pain and improve quality of life and sexual function.
PMID- 28419386
TI - Association between salinity and hospital admission for hypertension: an
ecological case-control study in the Mekong Delta Region in Vietnam.
AB - Background: Drinking water in the Mekong Delta Region (MDR) is highly vulnerable
to salinity intrusion and this problem is expected to increase with the projected
climate change and sea level rise. Despite this, research on health effects of
saline contaminated water is scarce in this region. This study examines the risk
of hospital admission for hypertension in salinity-affected areas of the MDR.
Methods: Cases and controls were obtained from national/provincial hospital
admission records for 2013. The cases were adult patients whom hypertension
(ICD10-code: I10-I15) was primary diagnosis for admission. Of the 13 provinces in
the MDR, we identified seven as 'salinity exposed' and the remaining as 'non
exposed' areas. A multi-level logistic regression model was used to examine the
association between salinity exposure and hypertension outcome. Results: Of the
total 573 650 hospital admissions, 22 382 (~3.9%) were hypertensive cases. The
multi-level logistic model combining both individual and ecological factors
showed a 9% increase in risk (95% CI: 3-14%) of hypertension admission among
individuals in exposed areas compared to those in non-exposed areas. Conclusion:
In order to develop and promote appropriate adaptation strategies, further
research is recommended to identify the salt exposure pathways and consumption
behaviours in the salinity exposed areas.
PMID- 28419387
TI - Effect of Continuous Positive Airway Pressure Treatment on Health-Related Quality
of Life and Sleepiness in High Cardiovascular Risk Individuals With Sleep Apnea:
Best Apnea Interventions for Research (BestAIR) Trial.
AB - Study Objectives: The long-term effect of continuous positive airway pressure
(CPAP) on health-related quality of life (HRQOL) in patients with high
cardiovascular disease risk and obstructive sleep apnea (OSA) without severe
sleepiness is uncertain. We aimed to determine the effect of CPAP treatment on
HRQOL in individuals with moderate or severe OSA and cardiovascular disease (CVD)
or multiple CVD risk factors without severe sleepiness. Methods: In this
randomized, controlled, parallel group study, 169 participants were assigned to
treatment with CPAP or the control group (conservative medical therapy [CMT] or
CMT with sham CPAP). Analyses were based on an intention-to-treat approach.
Linear mixed effect models were fitted to compare the changes in the Medical
Outcomes Study Short Form-36 (SF-36) and in subjective sleepiness (Epworth
Sleepiness Scale [ESS]) between groups from baseline to the average of 6- and 12
month measurements. Results: CPAP improved several domains of HRQOL including
bodily pain (treatment effect 9.7 [95% confidence interval, CI 3.9 to 15.4]; p =
.001), vitality (5.7 [95% CI 1.5 to 9.9]; p = .008), general health (8.2 [95% CI
3.7 to 12.7]; p < .001), physical functioning (5.5 [95% CI 1.1 to 10.0]; p =
.016), and the physical health summary score (3.3 [95% CI 1.4 to 5.3]; p = .001).
CPAP also resulted in less daytime sleepiness (mean change in ESS -1.0 point [95%
CI -2.0 to -0.0]; p = .040). Conclusions: In patients with moderate-severe OSA at
high risk of cardiovascular events and without severe sleepiness, CPAP improved
daytime sleepiness and multiple domains of HRQOL over 6 to 12 months of follow
up, with the largest improvement observed for bodily pain.
PMID- 28419388
TI - Daytime Sleepiness Increases With Age in Early Adolescence: A Sleep Restriction
Dose-Response Study.
AB - Study Objectives: Daytime sleepiness increases across adolescence. This increase
is commonly attributed to insufficient sleep durations resulting from
increasingly limited time in bed. We tested the effects of 3 sleep schedules on
daytime sleepiness and whether these effects changed with age in early
adolescence. Methods: In 77 children ranging in age from 9.9 to 14 years,
objective (multiple sleep latency test [MSLT]) and subjective (Karolinska
sleepiness scale [KSS]) sleepiness was measured following 4 consecutive nights of
either 7, 8.5, or 10 hours in bed. All participants completed all 3 sleep
schedules. The order in which they completed the schedules was not randomized but
was accounted for in all statistical analyses. Results: Time in bed restriction
decreased sleep duration and increased objective and subjective daytime
sleepiness. Although the sleep durations did not change with age, the likelihood
of falling asleep during the MSLT increased with age. Nevertheless, sleep
restriction produced a greater increase in MSLT-measured sleepiness in younger
participants. Subjective sleepiness measured with the KSS increased with shorter
sleep duration, but this effect did not change with age. Conclusions: Increasing
objective daytime sleepiness in early adolescence cannot simply be attributed to
reduced sleep due to restricted sleep schedules. We propose that some of the
increased daytime sleepiness of adolescents is a consequence of adolescent brain
reorganization driven by synaptic pruning which decreases the intensity of waking
brain activity.
PMID- 28419389
TI - Letter: Guidelines for the Management of Severe Traumatic Brain Injury, Fourth
Edition.
PMID- 28419390
TI - Adolescent Stress as a Driving Factor for Schizophrenia Development-A Basic
Science Perspective.
AB - Schizophrenia has been associated with heightened stress responsivity in
adolescence that precedes onset of psychosis. We now report that multiple
stressors during adolescence in normal rats leads to deficits in adults analogous
to that seen in schizophrenia patients. Moreover, impairment of stress control by
lesion of the prelimbic prefontal cortex in adolescence caused previously
subthreshold levels of stress to induce these deficit states when tested as
adults. Thus, predisposition to stress hyper-responsivity, or exposure to
substantial stressors, during adolescence can trigger a cascade of events that
result in a schizophrenia-like profile in adults. This data can provide crucial
information with respect to identifying markers for schizophrenia vulnerability
early in life and, by mitigating the impact of stressors, prevent the transition
to psychosis.
PMID- 28419391
TI - Letter to the Editor: Short-Term Outcomes of Aflibercept Therapy for Diabetic
Macular Edema in Patients With Incomplete Response to Ranibizumab and/or
Bevacizumab.
PMID- 28419392
TI - Erratum for "Eight Questions With Darius Moshfeghi".
PMID- 28419393
TI - Role of Disorganization of Retinal Inner Layers as an Optical Coherence
Tomography Biomarker in Diabetic and Uveitic Macular Edema.
PMID- 28419394
TI - Use of Corticosteroids in the Treatment of Patients With Diabetic Macular Edema
Who Have a Suboptimal Response to Anti-VEGF: Recommendations of an Expert Panel.
AB - BACKGROUND AND OBJECTIVE: Guidance on the use of corticosteroids in the treatment
of diabetic macular edema (DME) is lacking. This study aimed to develop a
clinically recommended treatment paradigm for DME with emphasis on the role of
corticosteroids. PATIENTS AND METHODS: An expert panel of nine retinal
specialists in the United States developed consensus recommendations for DME
treatment through a modified Delphi process. RESULTS: The panelists typically use
intravitreal injections of vascular endothelial growth factor (VEGF) antagonists
as first-line treatment of DME and switch patients with an inadequate response to
anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or
better because of edema after three to six monthly injections, or a less-than-50%
reduction in excess macular thickness after three to four monthly injections) to
intravitreal corticosteroid treatment. CONCLUSION: Intravitreal corticosteroids
have a potentially useful role in the treatment of patients with DME who have an
inadequate response to intravitreal anti-VEGF therapy. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:291-301.].
PMID- 28419395
TI - Choriocapillaris Changes Imaged by OCT Angiography After Half-Dose Photodynamic
Therapy for Chronic Central Serous Chorioretinopathy.
AB - BACKGROUND AND OBJECTIVE: To evaluate the choriocapillaris using optical
coherence tomographic angiography (OCTA) after half-dose verteporfin photodynamic
therapy (hd-PDT) for chronic central serous chorioretinopathy (CSC). PATIENTS AND
METHODS: We studied six eyes (six patients) with chronic CSC treated by hd-PDT.
OCTA was performed before, 1 week after, and 1 month after hd-PDT. The area of
flow abnormality at the choriocapillaris level within the PDT spot after hd-PDT
was compared with that before hd-PDT. RESULTS: Serous retinal detachment was
diminished in all eyes, with three achieving complete resolution at 1 month. On
OCTA, all eyes showed irregular choriocapillaris flow before hd-PDT. The areas of
abnormal flow shrank progressively at 1 month after hd-PDT. CONCLUSION: On OCTA,
choriocapillaris flow tended to recover at 1 month after hd-PDT. OCTA may be
clinically useful for evaluating choriocapillaris and the therapeutic effects of
hd-PDT for chronic CSC. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:302
310.].
PMID- 28419396
TI - Correlation Between Mesopic Retinal Sensitivity and Optical Coherence Tomographic
Metrics of the Outer Retina in Patients With Non-Atrophic Dry Age-Related Macular
Degeneration.
AB - BACKGROUND AND OBJECTIVE: To determine the correlation between mesopic retinal
sensitivity and optical coherence tomographic metrics of the outer retina in
patients with intermediate age-related macular degeneration (AMD). PATIENTS AND
METHODS: Participants with nonatrophic dry AMD underwent mesopic MP-3
microperimetry (Nidek, Padova, Italy) and both Nidek and Cirrus (Carl Zeiss
Meditec, Dublin, CA) spectral-domain optical coherence tomography (SD-OCT). The
volume of the outer retinal layers was measured on the Nidek SD-OCT scans using
the automatic segmentation algorithm of Navis-EX software. In addition, drusen
area and volume within a 5-mm circle centered on the fovea were determined using
the Cirrus Advanced RPE Analysis Tool. The mean retinal sensitivity at 8 degrees
and 10 degrees of fixation (5-mm and 6-mm circles) was calculated for every eye.
The correlation between retinal sensitivity and patient age, outer retinal layer
volume, drusen area, and drusen volume was assessed. RESULTS: Thirty-seven eyes
from 25 patients with non-atrophic dry AMD were included in the study. The mean
age of the patients was 76 years +/- 9 years. The mean sensitivity across the
whole tested retinal area was 24.9 dB +/- 2.4 dB, with a sensitivity of 25.1 dB
+/- 2.4 dB within the central 5-mm circle. Drusen area within the central 5-mm
circle was 0.7 mm2 +/- 0.89 mm2 with a drusen volume of 0.03 mm3 +/- 0.04 mm3.
Retinal pigment epithelium and photoreceptor outer segment (RPE + OS) volume was
1.96 mm3 +/- 0.1 mm3, and outer nuclear layer (ONL) volume was 1.91 mm3 +/- 0.17
mm3. There was a significant correlation between RPE + OS volume and retinal
sensitivity, as well as between patients' age and retinal sensitivity. There was
no significant correlation between drusen area or volume and retinal sensitivity,
nor between ONL volume and retinal sensitivity. CONCLUSION: In eyes with
nonatrophic AMD, retinal sensitivity is correlated with the RPE + OS volume, but
not the ONL volume or the area or volume of drusen. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:312-318.].
PMID- 28419397
TI - Influence of Retinal Pathology on the Reliability of Macular Thickness
Measurement: A Comparison Between Optical Coherence Tomography Devices.
AB - BACKGROUND AND OBJECTIVE: To evaluate the repeatability, reliability, and
comparability of macular thickness measurements between three optical coherence
tomography (OCT) machines in healthy eyes, eyes with diabetic macular edema
(DME), and eyes with neovascular age-related macular degeneration (nAMD).
PATIENTS AND METHODS: Twenty-three eyes with DME, 26 eyes with nAMD, and 24
healthy eyes as controls were evaluated. Scans were performed using the swept
source Triton (Topcon, Tokyo, Japan), the spectral-domain Cirrus (Carl Zeiss
Meditec, Dublin, CA), and the Spectralis (Heidelberg Engineering, Heidelberg,
Germany) machines. Scans were evaluated for central macular thickness (CMT),
presence of segmentation and fixation imaging artifacts (IA), re-scan
reliability, and agreement between machines and groups. RESULTS: Mean CMT was
significantly different between all OCT machines in all groups (P < .01 for all
comparisons). Manually correcting IA did not alter these results. There was good
scan repeatability among healthy and DME eyes for each machine, but poor
repeatability among the nAMD group with the Spectralis (P = .038). IA were
significantly increased in the presence of pathology. CONCLUSIONS: There is poor
agreement of CMT measurement between OCT machines in healthy eyes and those with
DME and nAMD. DME and nAMD have a significant effect on the rate of IA in scans.
Care is required when interpreting measurements from different OCT devices in
clinical practice and research settings. [Ophthalmic Surg Lasers Imaging Retina.
2017;48:319-325.].
PMID- 28419398
TI - Pre-Existing RPE Atrophy and Defects in the External Limiting Membrane Predict
Early Poor Visual Response to Ranibizumab in Neovascular Age-Related Macular
Degeneration.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to identify the rate of
early visual acuity poor responders in patients with neovascular age-related
macular degeneration (AMD) after the first intravitreal injection of ranibizumab
(Lucentis; Genentech, South San Francisco, CA) and to determine potential
predictors for early response. PATIENTS AND METHODS: Patients with choroidal
neovascularization secondary to AMD were evaluated before and 1 month after their
first ranibizumab treatment. Early poor responders were defined as eyes gaining
less than five letters 1 month after the first injection. RESULTS: Following the
first ranibizumab injection, 58% of 84 patients gained five or more letters.
Beyond 42% poor responders, 31% displayed foveal retinal pigment epithelium (RPE)
atrophy and 89% a loss of the external limiting membrane (ELM) integrity at
baseline. However, the amount of intra- and subretinal fluid, pigment epithelial
detachment (PED), and subfoveal fibrosis showed a similar distribution between
gainers and poor responders. CONCLUSION: Early poor responders present with more
RPE atrophy, as well as a loss of the ELM integrity at baseline optical coherence
tomography. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:326-332.].
PMID- 28419399
TI - Low Fluence Photodynamic Therapy Versus Graded Subthreshold Transpupillary
Thermotherapy for Chronic Central Serous Chorioretinopathy: Results From a
Prospective Study.
AB - BACKGROUND AND OBJECTIVE: The authors compare low fluence photodynamic therapy
(PDT) against graded subthreshold transpupillary thermotherapy (TTT) for chronic
central serous chorioretinopathy (CSC). PATIENTS AND METHODS: Forty-two eyes of
42 patients with chronic CSC were included in this prospective, nonrandomized,
interventional trial. All patients were offered PDT as an initial intervention.
If they declined PDT, TTT was offered. RESULTS: Twenty patients underwent PDT and
22 underwent TTT. The difference in best-corrected visual acuity between the TTT
and PDT groups at baseline and at 6 months after treatment was not significant (P
= .728). The mean foveal thickness decreased significantly in both groups (P =
.001). However, patients in the TTT group required more treatments (P = .013) and
longer time for resolution of the CSC (P = .013). CONCLUSIONS: Both PDT and TTT
may be equally effective in the treatment of chronic CSC. Graded subthreshold TTT
may be a cost-effective and safe alternative for PDT. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:334-338.].
PMID- 28419400
TI - A Nine-Year Follow-Up of Macular Complications in Retinitis Pigmentosa and
Diabetes Mellitus.
AB - The authors report a 9-year follow-up of macular complications in a 66-year-old
woman affected with retinitis pigmentosa (RP) and type 2 diabetes mellitus.
Rarely, clinical signs of diabetic retinopathy are presented in a patient with
retinal dystrophy. This patient developed a bilateral diabetic macular edema
(DME), which made its management complex due to the multiple pathogenic processes
involved. Despite the chronicity of the DME, visual acuity remained stable
without therapy. To the authors' knowledge, this is the first report of DME in RP
with such a long follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:340
344.].
PMID- 28419401
TI - Unilateral Pigmented Paravenous Retinochoroidal Atrophy Associated With Presumed
Ocular Tuberculosis.
AB - This report describes a case of unilateral pigmented paravenous retinochoroidal
atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31
year-old woman, previously diagnosed with intermediate uveitis in the right eye
(OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus
examination, fluorescein angiography, autofluorescence, and optical coherence
tomography OD were in keeping with a phenotypic diagnosis of PPRCA.
Electrophysiology showed severe photoreceptor dysfunction of both the rod and the
cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the
first report of unilateral PPRCA secondary to presumed ocular tuberculosis.
[Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.].
PMID- 28419402
TI - Autologous Free Internal Limiting Membrane Flap for Optic Nerve Head Pit With
Maculopathy.
AB - Optic disc pits (ODPs) are associated with serous macular detachment (SMD), which
causes visual loss in 25% to 75% patients with ODPs. There are various modalities
of noninvasive and invasive treatment options; however, the best method of
treatment is to seal the optic disc to prevent further egress of fluid into the
subretinal space. The authors report a technique that involves sealing of ODPs
with autologous free flap of the internal limiting membrane (ILM). After trans
pars plana vitrectomy, the ILM was peeled and plugged into the ODP. This
procedure gave good anatomical and functional success. [Ophthalmic Surg Lasers
Imaging Retina. 2017;48:350-353.].
PMID- 28419403
TI - Adaptive Optics of Small Choroidal Melanoma.
AB - The authors report the use of an adaptive optics (AO) system in an asymptomatic
patient with small choroidal melanoma. A noninvasive, novel assessment that
detected potential photoreceptor abnormalities in the retina overlying the
choroidal lesion and adjacent retina is presented. These findings may help
current clinical evaluation to monitor structural damage to the outer retina and
possibly justify earlier intervention in borderline cases. Future research is
warranted to recognize full potential of this imaging modality. [Ophthalmic Surg
Lasers Imaging Retina. 2017;48:354-357.].
PMID- 28419404
TI - Use of Evicel Fibrin Sealant in Optic Disc Pit-Associated Macular Detachment.
AB - Optic disc pit is a rare congenital anomaly of the optic nerve. Retinal
detachment is a common complication with poor outcomes. Many surgical
alternatives have been described for the treatment of this condition, producing
variable results. Herein, the authors describe four cases of optic disc pit
associated macular detachment managed with pars plana vitrectomy, fluid-air
exchange, drainage of subretinal fluid through the optic disc pit, temporal
peripapillary laser, and application of Evicel fibrin sealant (human) (Ethicon,
Bridgewater, NJ) over the optic disc head. Case 1 showed stable visual acuity and
improvement of subretinal fluid. Cases 2 and 3 showed visual acuity and
subretinal fluid improvements. At the 1-week follow-up visit, Case 4 showed
almost total subretinal fluid absorption. The sealant invariably disappeared
between 1 and 2 weeks and was tolerated by all patients. This case series
suggests that Evicel fibrin sealant may be considered as an adjunctive option in
the surgical treatment of optic disc pit-associated maculopathy. [Ophthalmic Surg
Lasers Imaging Retina. 2017;48:358-363.].
PMID- 28419405
TI - Optical Coherence Tomography Angiography Features in Melanocytoma of the Optic
Nerve.
AB - Optic disc melanocytoma (ODM) is a pigmented tumor with malignant potential
characterized clinically as a dark brown to black lesion with feathery margins.
The authors report a case of ODM and describe the utility of optical coherence
tomography angiography (OCTA) in detecting superficial tumor vascularization.
This case report demonstrated the ability of OCTA to reveal the fine abnormal
retinal vasculature on the surface of the lesion, a characteristic of ODM, which
has been previously correlated with tumor growth. [Ophthalmic Surg Lasers Imaging
Retina. 2017;48:364-366.].
PMID- 28419406
TI - Routine oro/nasopharyngeal suction versus no suction at birth.
AB - BACKGROUND: Oro/nasopharyngeal suction is a method used to clear secretions from
the oropharynx and nasopharynx through the application of negative pressure via a
suction catheter or bulb syringe. Traditionally, airway oro/nasopharyngeal
suction at birth has been used routinely to remove fluid rapidly from the
oropharynx and nasopharynx in vigorous and non-vigorous infants at birth.
Concerns relating to the reported adverse effects of oro/nasopharyngeal
suctioning led to a practice review and routine oro/nasopharyngeal suctioning is
no longer recommended for vigorous infants. However, it is important to know
whether there is any clear benefit or harm for infants whose oro/nasopharyngeal
airway is suctioned compared to infants who are not suctioned. OBJECTIVES: To
evaluate the effect of routine oropharyngeal/nasopharyngeal suction compared to
no suction on mortality and morbidity in newly born infants. SEARCH METHODS: We
used the standard search strategy of the Cochrane Neonatal Review group to search
the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 3),
MEDLINE via PubMed (1966 to April 18, 2016), Embase (1980 to April 18, 2016), and
CINAHL (1982 to April 18, 2016). We also searched clinical trials databases,
conference proceedings, and the reference lists of retrieved articles for
randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA:
Randomised, quasi-randomised controlled trials and cluster randomised trials that
evaluated the effect of routine oropharyngeal/nasopharyngeal suction compared to
no suction on mortality and morbidity in newly born infants with and without
meconium-stained amniotic fluid. DATA COLLECTION AND ANALYSIS: The review authors
extracted from the reports of the clinical trials, data regarding clinical
outcomes including mortality, need for resuscitation, admission to neonatal
intensive care, five minute Apgar score, episodes of apnoea and length of
hospital stay. MAIN RESULTS: Eight randomised controlled trials met the inclusion
criteria and only included term infants (n = 4011). Five studies included infants
with no fetal distress and clear amniotic fluid, one large study included
vigorous infants with clear or meconium-stained amniotic fluid, and two large
studies included infants with thin or thick meconium-stained amniotic fluid.
Overall, there was no statistical difference between oro/nasopharyngeal suction
and no oro/nasopharyngeal suction for all reported outcomes: mortality (typical
RR 2.29, 95% CI 0.94 to 5.53; typical RD 0.01, 95% CI -0.00 to 0.01; I2 = 0%,
studies = 2, participants = 3023), need for resuscitation (typical RR 0.85, 95%
CI 0.69 to 1.06; typical RD -0.01, 95% CI -0.03 to 0.00; I2 = 0%, studies = 5,
participants = 3791), admission to NICU (typical RR 0.82, 95% CI 0.62 to 1.08;
typical RD -0.03, 95% CI -0.08 to 0.01; I2 = 27%, studies = 2, participants =
997) and Apgar scores at five minutes (MD -0.03, 95% CI -0.08 to 0.02; I2 not
estimated, studies = 3, participants = 330). AUTHORS' CONCLUSIONS: The currently
available evidence does not support or refute the benefits or harms of routine
oro/nasopharyngeal suction over no suction. Further high-quality studies are
required in preterm infants or term newborn infants with thick meconium amniotic
fluid. Studies should investigate long-term effects such as neurodevelopmental
outcomes.
PMID- 28419407
TI - University of Chicago phase II consortium trial of selumetinib (MEKi)
demonstrates low tolerability and efficacy in relapsed DLBCL.
PMID- 28419408
TI - Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk
myelodysplastic syndromes: a retrospective, multicentre study.
AB - Iron chelation is controversial in higher risk myelodysplastic syndromes (HR
MDS), outside the allogeneic transplant setting. We conducted a retrospective,
multicentre study in 51 patients with transfusion-dependent, intermediate-to-very
high risk MDS, according to the revised international prognostic scoring system,
treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients
(71%) received azacitidine concomitantly. DFX was given at a median dose of 1000
mg/day (range 375-2500 mg) for a median of 11 months (range 0.4-75). Eight
patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom
(8%) required drug interruption. Median ferritin levels decreased from 1709 MUg/l
at baseline to 1100 MUg/l after 12 months of treatment (P = 0.02). Seventeen
patients showed abnormal transaminase levels at baseline, which improved or
normalized under DFX treatment in eight cases. One patient showed a remarkable
haematological improvement. At a median follow up of 35.3 months, median overall
survival was 37.5 months. The results of this first survey of DFX in HR-MDS are
comparable, in terms of safety and efficacy, with those observed in lower-risk
MDS. Though larger, prospective studies are required to demonstrate real clinical
benefits, our data suggest that DFX is feasible and might be considered in a
selected cohort of HR-MDS patients.
PMID- 28419409
TI - Anti-Mullerian hormone exhibits a great variation in infertile women with
different ovarian reserve patterns.
AB - BACKGROUND: Several conflicting studies with results on the biological
variability of serum anti-Mullerian hormone (AMH) levels have been reported. Most
of the studies have not focused on whether the level of AMH fluctuations shows
variability by a baseline ovarian follicular reserve. AIM: To reveal whether
intracyclic variation in AMH levels occurs among women with adequate, high and
diminished ovarian reserve patterns. STUDY DESIGN: In this prospective cross
sectional study, 171 infertile women between the ages of 18 and 42 years were
recruited. All participants were divided into three types of ovarian reserve
patterns (adequate, high and diminished). Serum samples were tested for levels of
follicular AMH (F-AMH), luteal AMH (L-AMH), estradiol (E2), and follicle
stimulating hormone (FSH) and progesterone. RESULTS: The median age of the 171
participating women was 28 (18-42) years. The three ovarian reserve groups had
similar body mass index (BMI) and E2 (P = 0.797 and P = 0.135, respectively). The
serum AMH levels of all women and the three ovarian reserve groups in the
follicular phase were higher compared to those in the luteal phase (P < 0.001).
There were strong positive correlations between follicular and luteal AMH levels
in adequate, high and diminished reserve groups (Spearman r = 0.864, P < 0.001 vs
r = 0.899, P < 0.001 vs r = 0.863, P < 0.001, respectively). CONCLUSION: Serum
AMH levels were higher during the follicular phase than the luteal phase in women
with adequate, high and diminished ovarian patterns. Since the highest AMH levels
are demonstrated during the follicular phase, the optimal time to measure AMH
concentration might be during the follicular phase.
PMID- 28419411
TI - Pressure waveforms to assess epidural placement: is there a role on delivery
suite?
PMID- 28419410
TI - Selective and state-dependent activation of TRESK (K2P 18.1) background potassium
channel by cloxyquin.
AB - BACKGROUND AND PURPOSE: Cloxyquin (5-cloroquinolin-8-ol) has been described as an
activator of TRESK (K2P 18.1, TWIK-related spinal cord K+ channel) background
potassium channel. We have examined the specificity of the drug by testing
several K2P channels. We have investigated the mechanism of cloxyquin-mediated
TRESK activation, focusing on the differences between the physiologically
relevant regulatory states of the channel. EXPERIMENTAL APPROACH: Potassium
currents were measured by two-electrode voltage clamp in Xenopus oocytes and by
whole-cell patch clamp in mouse dorsal root ganglion (DRG) neurons. KEY RESULTS:
Cloxyquin (100 uM) activated mouse and human TRESK 4.4 +/- 0.3 (n = 28) and 3.9
+/- 0.3-fold (n = 8), respectively. The drug selectively targeted TRESK in the
K2P channel family and exerted state-dependent effects. TRESK was potently
activated by cloxyquin in the resting state. However, after robust activation of
the current by the calcium signal, evoked by stimulation of Gq-coupled receptors,
the compound did not influence mouse TRESK and only slightly affected the human
channel. The constitutively active mutant channels, mimicking the
dephosphorylated state (S276A) or containing altered channel pore (F156A and
F364A), were not further stimulated by cloxyquin. In a subpopulation of isolated
DRG neurons, cloxyquin substantially activated the background potassium current.
CONCLUSIONS AND IMPLICATIONS: Cloxyquin activates TRESK by a Ca2+ /calcineurin
independent mechanism. The drug is specific for TRESK within the K2P channel
family and useful for studying TRESK currents in native cells. The state
dependent pharmacological profile of this channel should be considered in the
development of therapeutics for migraine and other nociceptive disorders.
PMID- 28419412
TI - Eliminating malignant cells from cryopreserved ovarian tissue is possible in
leukaemia patients.
AB - Reimplantation of cryopreserved ovarian tissue (OT) can successfully restore
ovarian function in young cancer patients after gonadotoxic treatment. However,
for patients with leukaemia, there is a risk of malignant cell transmission. Our
objective was to evaluate minimal disseminated disease in OT from leukaemia
patients and test a follicle isolation technique to obtain disease-free follicle
suspensions. Cryopreserved OT from 12 leukaemia patients was thawed and analysed
by histology and long-term xenografting in immunosuppressed mice. In 10 patients,
follicles were isolated from OT, and polymerase chain reaction (PCR) was
performed on tissue, digested ovarian suspensions and isolated follicle
suspensions to investigate leukaemic cell presence. Mean patient age was 17.1
years. An average of 3.2 follicles were isolated per mm2 of cortex. Xenografting
of OT induced leukaemic masses in 2/12 mice. PCR identified leukaemic cell
presence in 66% of OT. Malignant cells were also detected in digested ovarian
suspensions. However, none of the follicle samples (>2300 follicles tested)
showed any malignant cell presence after washing. This study demonstrates that it
is possible to recover large numbers of viable follicles from cryopreserved OT of
leukaemia patients. All isolated and washed follicle suspensions tested negative
for leukaemic cells, giving leukaemia patients genuine hope of fertility
restoration.
PMID- 28419413
TI - Long-term outcomes, secondary malignancies and stem cell collection following
bendamustine in patients with previously treated non-Hodgkin lymphoma.
AB - Despite the long history of bendamustine as treatment for indolent non-Hodgkin
lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term
data from three clinical trials to characterize the toxicity and efficacy of
patients receiving bendamustine. Data were available for 149 subjects at 21
sites. The median age was 60 years at the start of bendamustine (range 39-84),
and patients had received a median of 3 prior therapies. The histologies included
grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small
lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell
lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n =
2) and not reported (n = 2). The median event-free survival was 14.1 months. Nine
of 12 attempted stem cell collections were successful. With a median follow-up of
8.9 years, 23 patients developed 25 cancers, including 8 patients with
myelodysplastic syndrome/acute myeloid leukaemia. These data provide important
information regarding the long-term toxicity of bendamustine in previously
treated patients. A small but meaningful number of patients achieved durable
remissions following bendamustine. These rigorously collected, patient-level,
long-term follow-up data provide reassurance that bendamustine or bendamustine
plus rituximab is associated with efficacy and safety for patients with relapsed
or refractory indolent non-Hodgkin lymphoma.
PMID- 28419414
TI - Association between aggressive care and bereaved families' evaluation of end-of
life care for veterans with non-small cell lung cancer who died in Veterans
Affairs facilities.
AB - BACKGROUND: To the authors' knowledge, little is known regarding the relationship
between patients' and families' satisfaction with aggressive end-of-life care.
Herein, the authors examined the associations between episodes of aggressive care
(ie, chemotherapy, mechanical ventilation, acute hospitalizations, and intensive
care unit admissions) within the last 30 days of life and families' evaluations
of end-of-life care among patients with non-small cell lung cancer (NSCLC).
METHODS: A total of 847 patients with NSCLC (34% of whom were aged <65 years) who
died in a nursing home or intensive care, acute care, or hospice/palliative care
(HPC) unit at 1 of 128 Veterans Affairs Medical Centers between 2010 and 2012
were examined. Data sources included Veterans Affairs administrative and clinical
data, Medicare claims, and the Bereaved Family Survey. The response rate for the
Bereaved Family Survey was 62%. RESULTS: Greater than 72% of veterans with
advanced lung cancer who died in an inpatient setting had at least 1 episode of
aggressive care and 31% received chemotherapy within the last 30 days of life.
For all units except for HPC, when patients experienced at least 1 episode of
aggressive care, bereaved families rated care lower compared with when patients
did not receive any aggressive care. For patients dying in an HPC unit, the
associations between overall ratings of care and >=2 inpatient admissions or any
episode of aggressive care were not found to be statistically significant. Rates
of aggressive care were not associated with age, and family ratings of care were
similar for younger and older patients. CONCLUSIONS: Aggressive care within the
last month of life is common among patients with NSCLC and is associated with
lower family evaluations of end-of-life care. Specialized care provided within an
HPC unit may mitigate the negative effects of aggressive care on these outcomes.
Cancer 2017;123:3186-94. (c) 2017 American Cancer Society.
PMID- 28419416
TI - The Seventh Year.
PMID- 28419415
TI - Allostery at opioid receptors: modulation with small molecule ligands.
AB - : Opioid receptors are 7-transmembrane domain receptors that couple to
heterotrimeric G proteins. The endogenous ligands for opioid receptors are
peptides which bind to the orthosteric site on the receptors. The MU-opioid
receptor is the target for opioid analgesics, while the delta-opioid receptor has
been suggested as a target for pain management, migraine and depression.
Similarly, kappa-opioid receptors are involved in pain and depression and
nociceptin receptors in pain and mood behaviours. However, exogenous orthosteric
ligands for opioid receptors cause a myriad of on-target side effects. Recently,
selective allosteric ligands for MU- and delta-opioid receptors have been
described. These compounds bind to a site on the receptor distinct from the
orthosteric site. Occupation of this allosteric site leads to modulation of
orthosteric ligand binding affinity and/or efficacy. Allosteric modulators may be
positive, negative or silent (neutral) (PAMs, NAMs or SAMs respectively). PAMs
may have in vivo activity by enhancing the activity of exogenous drugs or
endogenous opioid peptides. Enhancing endogenous opioid peptide activity
maintains the temporal and spatial distribution of these molecules but improves,
and potentially qualitatively changes, activity at their cognate receptors which
could limit side effects compared with traditional opioid drugs. In this review,
we describe the rationale and promise for the development of allosteric
modulators for opioid receptors, the discovery of selective allosteric
modulators, the identification of potential allosteric sites on opioid receptors
and the mode of action of the modulators. LINKED ARTICLES: This article is part
of a themed section on Emerging Areas of Opioid Pharmacology. To view the other
articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
PMID- 28419417
TI - Changes in the Relation Between Competence Beliefs and Achievement in Math Across
Elementary School Years.
AB - Math competence beliefs and achievement are important outcomes of school-based
learning. Previous studies yielded inconsistent results on whether skill
development, self-enhancement, or reciprocal effects account for the interplay
among them. A development-related change in the direction of their relation in
the early school years might explain the inconsistency. To test this, 542 German
elementary school students (M = 7.95 years, SD = 0.58) were repeatedly
investigated over 24 months from Grade 2 to Grade 4. Math competence beliefs
declined and had a growing influence on subsequent math grades. This suggests
changes in the dominant direction of the relation from a skill development to a
reciprocal effects model during elementary school. Findings are discussed with
regard to their theoretical and practical implications.
PMID- 28419418
TI - Does surgery for deep infiltrating bowel endometriosis improve fertility? A
systematic review.
AB - INTRODUCTION: Reduced fertility is a major concern in women with endometriosis.
The influence of surgery of deep infiltrating endometriosis (DIE) affecting the
bowel wall on fertility is controversial and the literature on this field is
heterogeneous. In this review we addressed whether surgery for bowel DIE improves
the spontaneous pregnancy rate, and the results of in vitro fertilization (IVF),
and the potential risk of such surgery. MATERIAL AND METHODS: We conducted a
literature search including the terms "deep", "deep infiltrating", "bowel",
rectovaginal", "endometriosis", "fertility", "infertility" and "IVF" in PubMed.
RESULTS: No randomized controlled studies were found. Other publications of
relevance included four retrospective and three prospective observational
studies. Moreover, one retrospective study compared results of IVF treatment with
or without previous surgery for bowel DIE. All studies reported detailed data on
surgical complications. The poor data quality precluded firm conclusions. The
results indicate, however, the possibility that surgery for bowel DIE may improve
the spontaneous pregnancy rate, and positive effects on IVF outcome cannot be
excluded. Such surgery will be associated with risk of major complications.
CONCLUSION: The lack of proper data precludes conclusions on the potential role
for bowel DIE surgery to improve the spontaneous pregnancy rate and results of
IVF treatment. Positive effects cannot be excluded, but the definite risk of
major complications must be taken into account.
PMID- 28419420
TI - Reliability of pressure waveform analysis to determine correct epidural needle
placement in labouring women.
AB - Pressure waveform analysis provides a reliable confirmatory adjunct to the loss
of-resistance technique to identify the epidural space during thoracic epidural
anaesthesia, but its role remains controversial in lumbar epidural analgesia
during labour. We performed an observational study in 100 labouring women of the
sensitivity and specificity of waveform analysis to determine the correct
location of the epidural needle. After obtaining loss-of-resistance, the
anaesthetist injected 5 ml saline through the epidural needle (accounting for the
volume already used in the loss-of-resistance). Sterile extension tubing,
connected to a pressure transducer, was attached to the needle. An investigator
determined the presence or absence of a pulsatile waveform, synchronised with the
heart rate, on a monitor screen that was not in the view of the anaesthetist or
the parturient. A bolus of 4 ml lidocaine 2% with adrenaline 5 MUg.ml-1 was
administered, and the epidural block was assessed after 15 min. Three women
displayed no sensory block at 15 min. The results showed: epidural block present,
epidural waveform present 93; epidural block absent, epidural waveform absent 2;
epidural block present, epidural waveform absent 4; epidural block absent,
epidural waveform present 1. Compared with the use of a local anaesthetic bolus
to ascertain the epidural space, the sensitivity, specificity, positive and
negative predictive values of waveform analysis were 95.9%, 66.7%, 98.9% and
33.3%, respectively. Epidural waveform analysis provides a simple adjunct to loss
of-resistance for confirming needle placement during performance of obstetric
epidurals, however, further studies are required before its routine
implementation in clinical practice.
PMID- 28419419
TI - The isoprenoid derivative N6 -benzyladenosine CM223 exerts antitumor effects in
glioma patient-derived primary cells through the mevalonate pathway.
AB - BACKGROUND AND PURPOSE: N6 -Isopentenyladenosine (i6A) is a modified nucleoside
exerting in vitro and in vivo antiproliferative effects. We previously
demonstrated that the actions of i6A correlate with the expression and activity
of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the
mevalonate (MVA) pathway, which is aberrant in brain cancer. To develop new anti
glioma strategies, we tested related compounds exhibiting greater activity than
i6A. EXPERIMENTAL APPROACH: We designed and synthesized i6A derivatives
characterized by the introduction of diverse chemical moieties in the N6 position
of adenosine and tested for their efficacy in U87 cells and in primary glioma
cultures, derived from patients. NMR-based structural analysis, molecular docking
calculations and siRNA mediated knockdown were used to clarify the molecular
basis of their action, targeting FPPS protein. KEY RESULTS: CM223, the i6A
derivative including a benzyl moiety in N6 position of adenine, showed marked
activity in selectively targeting glioma cells, but not normal human astrocytes.
This was due to induction of intrinsic pathways of apoptosis and inhibition of
proliferation, along with blockade of FPPS-dependent protein prenylation, which
counteracted oncogenic signalling mediated by EGF receptors. CONCLUSION AND
IMPLICATIONS: The biological effects together with structural data on interaction
of CM223 with FPPS, provided additional evidence for the correlation of the
i6A/CM223 antitumor activity with FPPS modulation. Because the MVA pathway is an
important promising target, CM223 and its derivatives should be considered
interesting active molecules in antiglioma research.
PMID- 28419421
TI - Upregulation of CD72 expression on CD19+ CD27+ memory B cells by CD40L in primary
immune thrombocytopenia.
AB - CD72 is a co-receptor of B cells and regulates B cell activation. Although
aberrant expression of CD72 has been reported in primary immune thrombocytopenia
(ITP), it is uncertain whether this aberrant expression is restricted to specific
B cell subsets. Furthermore, the mechanisms that regulate CD72 expression are
unknown. In this study, we found higher frequency of CD19+ B cells, CD19+ CD27+
memory B cells and lower frequency of CD19+ CD27- naive B cells in active ITP
patients compared with controls and patients in remission. CD72 expression on
CD19+ CD27+ cells was upregulated in active ITP patients and correlated with
platelet count and anti-platelet autoantibodies. In vitro, CD40L could
specifically induce CD72 upregulation on CD19+ CD27+ B cells. In combination with
CD40L, interleukin (IL) 10 and BAFF (also termed TNFSF13B) further enhanced CD72
expression on CD19+ CD27+ B cells, whereas IL21 reduced CD72 upregulation.
CD72mRNA expression after CD40L stimulation was increased in ITP patients and
controls. Significant increase of CD40L on CD4+ T cells was correlated with CD72
expression on CD19+ CD27+ B cells in ITP patients. In conclusion, upregulation of
CD72 expression on CD27+ memory B cells might take part in the pathogenesis of
ITP. Elevated CD40L on CD4+ cells combined with cytokines might contribute to the
upregulation of CD72 expression on CD27+ memory B cells.
PMID- 28419423
TI - Feeling run down: exercise-induced pancytopenia.
PMID- 28419422
TI - Early mortality and complications in hospitalized adult Californians with acute
myeloid leukaemia.
AB - Few studies have evaluated the impact of complications, sociodemographic and
clinical factors on early mortality (death <=60 days from diagnosis) in acute
myeloid leukaemia (AML) patients. Using data from the California Cancer Registry
linked to hospital discharge records from 1999 to 2012, we identified patients
aged >=15 years with AML who received inpatient treatment (N = 6359).
Multivariate logistic regression analyses were used to assess the association of
complications with early mortality, adjusting for sociodemographic factors,
comorbidities and hospital type. Early mortality decreased over time (25.3%, 1999
2000; 16.8%, 2011-2012) across all age groups, but was higher in older patients
(6.9%, 15-39, 11.4%, 40-54, 18.6% 55-65, and 35.8%, >65 years). Major bleeding
[Odds ratio (OR) 1.5, 95% confidence interval (CI) 1.3-1.9], liver failure (OR
1.9, 95% CI 1.1-3.1), renal failure (OR 2.4, 95% CI 2.0-2.9), respiratory failure
(OR 7.6, 95% CI 6.2-9.3) and cardiac arrest (OR 15.8, 95% CI 8.7-28.6) were
associated with early mortality. Higher early mortality was also associated with
single marital status, low neighbourhood socioeconomic status, lack of health
insurance and comorbidities. Treatment at National Cancer Institute-designated
cancer centres was associated with lower early mortality (OR 0.5, 95% CI 0.4
0.6). In conclusion, organ dysfunction, hospital type and sociodemographic
factors impact early mortality. Further studies should investigate how
differences in healthcare delivery affect early mortality.
PMID- 28419424
TI - Single centre experience of the management of superficial vein thrombosis with
prophylactic low-molecular-weight heparin.
PMID- 28419425
TI - How abnormal is binge eating? 18-Year time trends in population prevalence and
burden.
AB - OBJECTIVE: Although findings suggest that binge eating is becoming increasingly
normative, the 'clinical significance' of this behaviour at a population level
remains uncertain. We aimed to assess the time trends in binge-eating prevalence
and burden over 18 years. METHOD: Six cross-sectional face-to-face surveys of the
Australian adult population were conducted in 1998, 2005, 2008, 2009, 2014, and
2015 (Ntotal = 15 126). Data were collected on demographics, 3-month prevalence
of objective binge eating (OBE), health-related quality of life, days out of
role, and distress related to OBE. RESULTS: The prevalence of OBE increased six
fold from 1998 (2.7%) to 2015 (13.0%). Health-related quality of life associated
with OBE improved from 1998 to 2015, where it more closely approximated
population norms. Days out of role remained higher among participants who
reported OBE, although decreased over time. Half of participants who reported
weekly (56.6%) and twice-weekly (47.1%) OBE reported that they were not
distressed by this behaviour. However, the presence of distress related to OBE in
2015 was associated with greater health-related quality-of-life impairment.
CONCLUSION: As the prevalence of binge eating increases over time, associated
disability has been decreasing. Implications for the diagnosis of disorders
associated with binge eating are discussed.
PMID- 28419426
TI - Clinical characteristics, prognosis and treatment of myelofibrosis patients with
severe thrombocytopenia.
PMID- 28419427
TI - How I manage children with neutropenia.
AB - Neutropenia, usually defined as a blood neutrophil count <1.5 * 109 /l, is a
common medical problem for children and adults. There are many causes for
neutropenia, and at each stage in life the clinical pattern of causes and
consequences differs significantly. I recommend utilizing the age of the child
and clinical observations for the preliminary diagnosis and primary management.
In premature infants, neutropenia is quite common and contributes to the risk of
sepsis with necrotizing enterocolitis. At birth and for the first few months of
life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and
predisposes to the risk of severe bacterial infections. Thereafter when a child
is discovered to have neutropenia, often associated with relatively minor
symptoms, it is usually attributed to autoimmune disorder or viral infection. The
congenital neutropenia syndromes are usually recognized when there are recurrent
infections, the neutropenia is severe and there are congenital anomalies
suggesting a genetic disorder. This review focuses on the key clinical finding
and laboratory tests for diagnosis with commentaries on treatment, particularly
the use of granulocyte colony-stimulating factor to treat childhood neutropenia.
PMID- 28419428
TI - Platelets: much more than bricks in a breached wall.
AB - Platelets have various roles in vascular biology and homeostasis. They are the
first actor in primary haemostasis and play important roles in thrombosis
pathogenesis, but they are also part of innate immunity, which initiates and
accelerate many inflammatory conditions. In some contexts, their immune functions
are protective, while in others they contribute to adverse inflammatory outcomes.
Platelets express numerous receptors and contain hundreds of secretory molecules
that are crucial for platelet functional responses. The capacity of platelets to
produce and secrete cytokines, chemokines and related molecules, under the
control of specific intracellular pathways, is intimately related to their key
role in inflammation. They are also able to intervene in tissue regeneration and
repair because they produce pro-angiogenic mediators. Due to this characteristic
platelets are involved in cancer progression and spreading. In this review we
discuss the complex role of platelets, which bridges haemostasis, inflammation
and immune response both in physiological and pathological conditions.
PMID- 28419429
TI - Mutational landscape of B-cell post-transplant lymphoproliferative disorders.
AB - It is currently unclear whether post-transplant diffuse large B-cell lymphomas
(PT-DLBCL) display a similar genomic landscape as DLBCL in immunocompetent
patients (IC-DLBCL). We investigated 50 post-transplant lymphoproliferative
disorders (PTLDs) including 37 PT-DLBCL samples for somatic mutations frequently
observed in IC-DLBCL. Targeted Next Generation Sequencing (NGS) using the Ion
Torrent platform and a customized panel of 68 genes was performed on genomic DNA.
Non-tumoural tissue was sequenced to exclude germline variants in cases where
available. A control cohort of 76 IC-DLBCL was available for comparative
analyses. In comparison to IC-DLBCLs, PT-DLBCL showed more frequent mutations of
TP53 (P = 0.004), and absence of ATM and B2M mutations (P = 0.004 and P = 0.016,
respectively). In comparison to IC-DLBCLs, Epstein-Barr virus (EBV)+ PT-DLBCL had
fewer mutated genes (P = 0.007) and particularly fewer mutations in nuclear
factor-kappaB pathway-related genes (P = 0.044). TP53 mutations were more
frequent in EBV- PT-DLBCL as compared to IC-DLBCL (P = 0.001). Germinal centre B
cell (GCB) subtype of PT-DLBCL had fewer mutations and mutated genes than GCB-IC
DLBCLs (P = 0.048 and 0.04 respectively). Polymorphic PTLD displayed fewer
mutations as compared to PT-DLBCL (P = 0.001). PT-DLBCL differs from IC-DLBCL
with respect to mutations in genes related to DNA damage control and immune
surveillance, and EBV association is likely to have a bearing on the mutational
pattern.
PMID- 28419430
TI - The Role of Family Characteristics for Students' Academic Outcomes: A Person
Centered Approach.
AB - Using data from 1,571 ninth-grade students (Mage = 14.62) from 82 academic track
schools in Germany and their predominantly Caucasian middle-class parents,
configurations of different family characteristics reported by parents were
investigated. Latent profile analyses considering academic involvement, family
interest, parents' self-concept, child's need for support, and parents' time and
energy identified average, indifferent, motivated and engaged, motivated and
disengaged, and involved families. Cross-sectional and longitudinal associations
with students' motivational (self-concept, effort, and interest) and achievement
outcomes (achievement test and grades) in math were analyzed. Students from
families classified as motivated and disengaged showed higher initial levels
motivation and achievement. Over 5 months, these students also showed an increase
in self-concept and higher achievement than students from other family types.
PMID- 28419431
TI - Moving Beyond Maximum Tolerated Dose for Targeted Oncology Drugs: Use of Clinical
Utility Index to Optimize Venetoclax Dosage in Multiple Myeloma Patients.
AB - Exposure-response analyses of venetoclax in combination with bortezomib and
dexamethasone in previously treated patients with multiple myeloma (MM) were
performed on a phase Ib venetoclax dose-ranging study. Logistic regression models
were utilized to determine relationships, identify subpopulations with different
responses, and optimize the venetoclax dosage that balanced both efficacy and
safety. Bortezomib refractory status and number of prior treatments were
identified to impact the efficacy response to venetoclax treatment. Higher
venetoclax exposures were estimated to increase the probability of achieving a
very good partial response (VGPR) or better through venetoclax doses of 1,200 mg.
However, the probability of neutropenia (grade >=3) was estimated to increase at
doses >800 mg. Using a clinical utility index, a venetoclax dosage of 800 mg
daily was selected to optimally balance the VGPR or better rates and neutropenia
rates in MM patients administered 1-3 prior lines of therapy and nonrefractory to
bortezomib.
PMID- 28419432
TI - A Global Synthesis of Managing Groundwater Dependent Ecosystems Under Sustainable
Groundwater Policy.
AB - Groundwater is a vital water supply worldwide for people and nature. However,
species and ecosystems that depend on groundwater for some or all of their water
needs, known as groundwater dependent ecosystems (GDEs), are increasingly
becoming threatened worldwide due to growing human water demands. Over the past
two decades, the protection and management of GDEs have been incorporated into
several water management policy initiatives worldwide including jurisdictions
within Australia, the European Union, South Africa, and the United States. Among
these, Australia has implemented the most comprehensive framework to manage and
protect GDEs through its water policy initiatives. Using a science-based
approach, Australia has made good progress at reducing uncertainty when selecting
management thresholds for GDEs in their water management plans. This has been
achieved by incorporating appropriate metrics for GDEs into water monitoring
programs so that information gathered over time can inform management decisions.
This adaptive management approach is also accompanied by the application of the
"Precautionary Principle" in cases where insufficient information on GDEs exist.
Additionally, the integration of risk assessment into Australia's approach has
enabled water managers to prioritize the most valuable and vulnerable ecologic
assets necessary to manage GDEs under Australia's national sustainable water
management legislation. The purpose of this paper is to: (1) compare existing
global policy initiatives for the protection and management of GDEs; (2)
synthesize Australia's adaptive management approach of GDEs in their state water
plans; and (3) highlight opportunities and challenges of applying Australia's
approach for managing GDEs under other water management policies worldwide.
PMID- 28419433
TI - Plant-soil feedbacks in declining forests: implications for species coexistence.
AB - Plant-soil feedbacks (PSFs) play a relevant role as drivers of species abundance,
coexistence, and succession in plant communities. However, the potential
contribution of PSFs to community dynamics in changing forest ecosystems affected
by global change drivers is still largely unexplored. We measured the direction,
strength and nature (biological vs. chemical) of PSFs experienced by coexisting
tree species in two types of declining Quercus suber forests of southwestern
Spain (open woodland vs. closed forest) invaded by the exotic soil pathogen
Phytophthora cinnamomi. To test PSFs in a realistic community context, we focused
not only on individual PSFs (i.e., comparing the growth of a tree species on
conspecific vs. heterospecific soil) but also calculated net-pairwise PSFs by
comparing performance of coexisting tree species on their own and each other's
soils. We hypothesized that the decline and death of Q. suber would alter the
direction and strength of individual and net-pairwise PSFs due to the associated
changes in soil nutrients and microbial communities, with implications for
recruitment dynamics and species coexistence. In support of our hypothesis, we
found that the decline of Q. suber translated into substantial alterations of
individual and net-pairwise PSFs, which shifted from mostly neutral to
significantly positive or negative, depending on the forest type. In both cases
however the identified PSFs benefited other species more than Q. suber (i.e.,
heterospecific positive PSF in the open woodland, conspecific negative PSF in the
closed forest). Our results supported PSFs driven by changes in chemical soil
properties (mainly phosphorus) and arbuscular mycorrhizal fungi, but not in
pathogen abundance. Overall, our study suggests that PSFs might reinforce the
loss of dominance of Q. suber in declining forests invaded by P. cinnamomi by
promoting the relative performance of non-declining coexisting species. More
generally, our results indicate an increase in the strength of net PSFs as
natural forests become disturbed by global change drivers (e.g., invasive
species), suggesting an increasingly important role of PSFs in forest community
dynamics in the near future.
PMID- 28419434
TI - Estimating species richness in hyper-diverse large tree communities.
AB - Species richness estimation is one of the most widely used analyses carried out
by ecologists, and nonparametric estimators are probably the most used techniques
to carry out such estimations. We tested the assumptions and results of
nonparametric estimators and those of a logseries approach to species richness
estimation for simulated tropical forests and five data sets from the field. We
conclude that nonparametric estimators are not suitable to estimate species
richness in tropical forests, where sampling intensity is usually low and
richness is high, because the assumptions of the methods do not meet the sampling
strategy used in most studies. The logseries, while also requiring substantial
sampling, is much more effective in estimating species richness than commonly
used nonparametric estimators, and its assumptions better match the way field
data is being collected.
PMID- 28419435
TI - Osteogenic differentiation potential of mesenchymal stem cells cultured on
nanofibrous scaffold improved in the presence of pulsed electromagnetic field.
AB - Nowadays, tissue engineering by using stem cells in combination with scaffolds
and bioactive molecules has made significant contributions to the regeneration of
damaged bone tissues. Since the usage of bioactive molecules including, growth
factors to induce differentiation is safety limited in clinical applications, and
it has also been previously observed that extremely low frequency pulsed
electromagnetic fields (PEMF) can be effective in the enhancement of
proliferation rate and osteogenic differentiation of stem cells, the aim of this
study was investigating the osteoinductive potential of PEMF in combination with
Poly(caprolactone) (PCL) nanofibrous scaffold. To achieve this aim, Adipose
derived mesenchymal stem cells (ADSCs) isolated and characterized and then
osteogenic differentiation of them was investigated after culturing on the
surface of PCL scaffold under treatments of PEMF, PEMF plus osteogenic medium
(OM) and OM. Analysis of common osteogenic markers such as Alizarin red staining,
ALP activity, calcium content and four important bone-related genes in days of 7,
14, and 21 confirmed that the effects of PEMF on the osteogenic differentiation
of ADSCs are very similar to the effects of osteogenic medium. Thus, regarding
the immunological concerns about the application of bioactive molecules for
tissue engineering, PEMF could be a good alternative for osteogenic medium.
Although, results were showed a synergetic effect for simultaneous application of
PEMF and PCL scaffold in the osteogenesis process of ADSCs. Taking together,
ADSCs-seeded PCL nanofibrous scaffold in combination with PEMF could be a great
option for use in bone tissue engineering applications.
PMID- 28419436
TI - Ammonia oxidizer populations vary with nitrogen cycling across a tropical montane
mean annual temperature gradient.
AB - Functional gene approaches have been used to better understand the roles of
microbes in driving forest soil nitrogen (N) cycling rates and bioavailability.
Ammonia oxidation is a rate limiting step in nitrification, and is a key area for
understanding environmental constraints on N availability in forests. We studied
how increasing temperature affects the role of ammonia oxidizing archaea (AOA)
and bacteria (AOB) in soil N cycling and availability by using a highly
constrained natural mean annual temperature (MAT) elevation gradient in a
tropical montane wet forest. We found that net nitrate (NO3- ) bioavailability is
positively related to MAT (r2 = 0.79, P = 0.0033), and AOA DNA abundance is
positively related to both NO3- availability (r2 = 0.34, P = 0.0071) and MAT (r2
= 0.34, P < 0.001). In contrast, AOB DNA was only detected in some soils across
the gradient. We identified three distinct phylotypes within the AOA which
differed from one another in abundance and relative gene expression. In addition,
one AOA phylotype increased in abundance with MAT, while others did not. We
conclude that MAT is the primary driver of ecosystem N availability across this
gradient, and AOA population size and structure appear to mediate the
relationship between the nitrification and N bioavailability. These findings hold
important implications for nutrient limitation in forests and feedbacks to
primary production under changing climate.
PMID- 28419437
TI - A New Paradigm. "Learn - Learn More"; Dose-Exposure-Response at the Center of
Drug Development and Regulatory Approval.
AB - In his seminal paper, Lewis Sheiner introduced the "Learning versus Confirming"
paradigm. From that foundation, this work proposes why the precise estimation of
the dose-exposure-response (D-E-R) for both efficacy and safety endpoints should
be the ultimate goal for most drug development programs. The subsequent
identification and approval of an optimal dose regimen range will provide a
pragmatic framework for delivering personalized medicine based on dose titration
for each and every patient.
PMID- 28419438
TI - Dinosaur Tail Sign: A Useful Spinal MRI Finding Indicative of Cerebrospinal Fluid
Leakage.
AB - OBJECTIVE: To evaluate the imaging characteristics and diagnostic utility of the
"Dinosaur tail sign" in the diagnosis of cerebrospinal fluid (CSF) leakage.
BACKGROUND: The authors propose the "Dinosaur tail sign," defined as a
combination of the dorsal epidural hyperintensities, fat tissue, spinal cord, and
cauda equine on lumbosacral sagittal fat-suppressed T2-weighted image (FST2WI),
as a sensitive indicator for diagnosing CSF leakage. METHODS: Imaging
characteristics of the "Dinosaur tail sign" was evaluated in seven spontaneous
intracranial hypotension (SIH) and 23 iatrogenic CSF leakage (ICSFL) patients.
Additionally, the diagnostic index was compared between the "Dinosaur tail sign"
and other previously reported useful magnetic resonance imaging (MRI) and
magnetic resonance myelography (MRM) findings. RESULTS: In contrast to other
imaging findings including the epidural expansion, floating dural sac sign, and
distension of the spinal epidural veins on MRI, and paraspinal fluid collections
(PFC) on MRM, the "Dinosaur tail sign" was found equally in both SIH and ICSFL
patients (6 SIH and 19 ICSFL; 83% of all patients with CSF leakage). The
"Dinosaur tail sign" showed sufficient diagnostic utility (sensitivity 83%,
specificity 94%, accuracy 89%) that was comparable to that of PFC. CONCLUSION:
The "Dinosaur tail sign" is a useful imaging finding suggestive of CSF leakage.
Evaluation of subtle interspinous arched hyperintensities on spinal MRI is
mandatory for the diagnosis of SIH and ICSFL.
PMID- 28419439
TI - Effects of student pairing and public review on physical activity during school
recess.
AB - The purpose of this study was to evaluate the effects of student pairing and
feedback during recess on children's step counts. During baseline, participants
wore a sealed pedometer during recess. During intervention, we paired
participants with higher step counts with participants with lower step counts. We
encouraged teams to compete for the highest step count each day and provided
feedback on their performance during each recess session. Results showed a large
mean increase in step count from baseline to intervention. These results suggest
that children's steps during recess can be increased with a simple and cost
effective intervention.
PMID- 28419440
TI - The role of stromal cells in inflammatory bone loss.
AB - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
inflammation, local and systemic bone loss and a lack of compensatory bone
repair. Fibroblast-like synoviocytes (FLS) are the most abundant cells of the
stroma and a key population in autoimmune diseases such as RA. An increasing body
of evidence suggests that these cells play not only an important role in chronic
inflammation and synovial hyperplasia, but also impact bone remodelling. Under
inflammatory conditions FLS release inflammatory cytokines, regulate bone
destruction and formation and communicate with immune cells to control bone
homeostasis. Other stromal cells, such as osteoblasts and terminally
differentiated osteoblasts, termed osteocytes, are also involved in the
regulation of bone homeostasis and are dysregulated during inflammation. This
review highlights our current understanding of how stromal cells influence the
balance between bone formation and bone destruction. Increasing our understanding
of these processes is critical to enable the development of novel therapeutic
strategies with which to treat bone loss in RA.
PMID- 28419441
TI - Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of
acute lymphoblastic leukaemia patients: implications for minimal residual disease
detection.
AB - Flow cytometric detection of minimal residual disease (MRD) in children with B
cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic
discrimination between residual leukaemic cells and B-cell precursors (BCPs)
which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour
flow cytometry and innovative analysis tools were used to first characterize the
immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy
children, resulting in a continuous multiparametric pathway including transition
stages. This pathway was subsequently used as a reference to characterize the
immunophenotypic maturation of regenerating BCPs in BM from children treated for
BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in
contrast to the classical CD34high pre-B-I cell immunophenotype. These CD34-dim
pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I
subset), while hardly present in healthy control BM (9-13% within pre-B-I subset;
P = 0.0037). Furthermore, we showed that some of the BCP-ALL diagnosis
immunophenotypes (23%) overlapped with CD34-dim pre-B-I cells. Our results
indicate that newly identified CD34-dim pre-B-I cells can be mistaken for
residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes.
Therefore, regenerating BM, in which CD34-dim pre-B-I cells are relatively
abundant, should be used as reference frame in flow cytometric MRD measurements.
PMID- 28419442
TI - Characterization of Runx2 phosphorylation sites required for TGF-beta1-mediated
stimulation of matrix metalloproteinase-13 expression in osteoblastic cells.
AB - Transforming growth factor-beta1 (TGF-beta1), a highly abundant growth factor in
skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in
osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a
bone transcription factor, is required for TGF-beta1-mediated stimulation of MMP
13 expression in osteoblastic cells. In this study, the molecular mechanism
responsible for TGF-beta1-stimulation of MMP-13 expression via Runx2 in
osteoblastic cells was elucidated. TGF-beta1 stimulated the phosphorylation of
Runx2 at serine amino acids, and ERK inhibition blocked this effect in rat
(UMR106-01) and human (MG-63) osteoblastic cells. Pretreatment with okadaic acid,
a serine-threonine phosphatase inhibitor, increased Runx2 serine phosphorylation
in osteoblastic cells. When cells were pretreated with an ERK inhibitor, TGF
beta1-mediated stimulation of MMP-13 mRNA expression decreased. Nano-ESI/LC/MS
analysis identified that TGF-beta1 stimulates Runx2 phosphorylation at three
serine amino acids. Transient transfection of mouse mesenchymal stem cells
(C3H10T1/2) with Runx2 serine mutant constructs decreased TGF-beta1-mediated
Runx2 serine phosphorylation. A luciferase reporter assay identified that TGF
beta1 stimulated MMP-13 promoter activity in these cells only in the presence of
the wild Runx2 construct, and not with mutant Runx2. Thus, TGF-beta1 stimulates
the phosphorylation of Runx2 at three serine amino acids, and this event is
required for MMP-13 expression in osteoblastic cells. Hence, this study
contributes to the knowledge of events governing bone remodeling and bone-related
diseases.
PMID- 28419444
TI - A Self-Determination Theory Perspective on Postpartum Depressive Symptoms and
Early Parenting Behaviors.
AB - OBJECTIVE: On the basis of self-determination theory, this study investigates
longitudinal associations between satisfaction and frustration mothers' basic
psychological needs (i.e., autonomy, relatedness, competence) and mothers'
postnatal depressive symptoms and early parenting behaviors. METHOD: Participants
were 214 women assessed during their pregnancy (Time 1), 4 months after delivery
(Time 2), and when the child was 2 years old (Time 3). RESULTS: Results
demonstrate effects of prenatal basic psychological needs (needs frustration more
specifically) on postnatal depressive symptoms. In addition, general prenatal
needs satisfaction and frustration predicted more relationship-specific needs
satisfaction and frustration, respectively (in the mother-child relationship). In
turn, postnatal relationship-specific needs satisfaction predicted more high
quality parenting when the child is 2 years old. More specifically, needs
satisfaction was related to more maternal responsiveness and autonomy support.
CONCLUSION: Overall, these findings underscore the importance of psychological
needs experiences for both mothers' personal adjustment after birth and for the
early mother-child relationship.
PMID- 28419443
TI - Loss of natural killer T cells promotes pancreatic cancer in LSL-KrasG12D/+ mice.
AB - The role of the unique T-cell population, natural killer T (NKT) cells, which
have similar functions to NK cells in pancreatic cancer (PC), is not yet
evaluated. To address the regulatory roles of NKT cells on tumour progression
through tumour-associated macrophages (TAM) and their production of microsomal
prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven
pancreatic tumour (KPT) progression, we crossed CD1d-/- mice deficient in both
invariant and variant NKT cells with the KrasG12D mice. Loss of NKT cells
significantly increased pancreatic intraepithelial neoplasia (PanIN) lesions and
also increased 5-LOX and mPGES-1 expression in M2-type macrophages and cancer
stem-like cells in pancreatic tumours. Pharmacological inhibition of mPGES-1 and
5-LOX in M2 macrophages with specific inhibitor YS-121 in KPT-CD1d-/- mice
decreased PanIN lesions and suppressed tumour growth in association with elevated
levels of active CD8a cells. Hence, NKT cells regulate PC by modulating TAMs (M2)
through mPGES-1 and 5-LOX; and the absence of NKT cells leads to aggressive
development of PC.
PMID- 28419446
TI - From Autonomy to Divinity: The Cultural Socialization of Moral Reasoning in an
Evangelical Christian Community.
AB - This study examined moral reasoning in parent-child conversations within a U.S.
evangelical Christian community. The goal was to identify social-communicative
processes that may promote the development of Divinity in children's moral
reasoning. Sixteen parent-child dyads (6-9 years old) discussed hypothetical
moral vignettes about failures to help peers in need. Analyses revealed that
Divinity typically co-occurred with Autonomy in these conversations and that such
co-occurrences typically happened through three distinct social-communicative
processes, labeled "align," "scaffold," and "counter." Findings are used to
explain the shifting priority of Autonomy and Divinity over the life course among
members of evangelical Christian faiths that previous research has documented.
More broadly, findings highlight socialization processes through which children
can rationalize their developing moral outlooks in culturally distinct ways.
PMID- 28419445
TI - Activation of ClC-3 chloride channel by 17beta-estradiol relies on the estrogen
receptor alpha expression in breast cancer.
AB - Although extensively studied, the mechanisms by which estrogen promotes breast
cancer growth remain to be fully elucidated. Tamoxifen, an antiestrogen agent to
treat ERalpha+ breast cancer, is also a high-affinity blocker of the chloride
channels. In this study, we explored the involvement of the chloride channels in
the action of estrogen in breast cancer. We found that 17beta-estradiol (17beta
E2) concentration-dependently activated the chloride currents in ERalpha+ breast
cancer MCF-7 cells. Extracellular hypertonic challenge and chloride channel
blockers, NPPB and DIDS inhibited the 17beta-E2-activated chloride currents.
Decreased the ClC-3 protein expression caused the depletion of the 17beta-E2
activated chloride currents. 17beta-E2-activated chloride currents which relied
on the ERalpha expression were demonstrated by the following evidences. Firstly,
17beta-E2-activated chloride currents could not be observed in ERalpha- breast
cancer MDA-MB-231 cells. Secondly, ER antagonists, tamoxifen and ICI 182,780, and
downregulation of ERalpha expression inhibited or abolished the 17beta-E2
activated chloride currents. Thirdly, ERalpha expression was induced in MDA-MB
231 cells by ESR1 gene transfection, and then 17beta-E2-activated chloride
currents could be observed. In MCF-7 cells, ERalpha and ClC-3 mainly located in
nucleus and translocated to cell plasma and membrane with respect to co
localization following treatment of 17beta-E2. Downregulation of ERalpha
expression could decrease the expression of ClC-3 protein. Conversely,
downregulation of ClC-3 expression did not influence the ERalpha expression.
Taken together, our findings demonstrated that ClC-3 is a potential target of
17beta-E2 and is modulated by the ERalpha in breast cancer cell. Pharmacological
modulation of ClC-3 may provide a deep understanding in antiestrogen treatment of
breast cancer patients.
PMID- 28419447
TI - Divergence and evolution of assortative mating in a polygenic trait model of
speciation with gene flow.
AB - Assortative mating is an important driver of speciation in populations with gene
flow and is predicted to evolve under certain conditions in few-locus models.
However, the evolution of assortment is less understood for mating based on
quantitative traits, which are often characterized by high genetic variability
and extensive linkage disequilibrium between trait loci. We explore this scenario
for a two-deme model with migration, by considering a single polygenic trait
subject to divergent viability selection across demes, as well as assortative
mating and sexual selection within demes, and investigate how trait divergence is
shaped by various evolutionary forces. Our analysis reveals the existence of
sharp thresholds of assortment strength, at which divergence increases
dramatically. We also study the evolution of assortment via invasion of modifiers
of mate discrimination and show that the ES assortment strength has an
intermediate value under a range of migration-selection parameters, even in
diverged populations, due to subtle effects which depend sensitively on the
extent of phenotypic variation within these populations. The evolutionary
dynamics of the polygenic trait is studied using the hypergeometric and
infinitesimal models. We further investigate the sensitivity of our results to
the assumptions of the hypergeometric model, using individual-based simulations.
PMID- 28419448
TI - Understanding the Transfer Deficit: Contextual Mismatch, Proactive Interference,
and Working Memory Affect Toddlers' Video-Based Transfer.
AB - Researchers tested the impact of contextual mismatch, proactive interference, and
working memory (WM) on toddlers' transfer across contexts. Forty-two toddlers (27
34 months) completed four object-retrieval trials, requiring memory updating on
Trials 2-4. Participants watched hiding events on a tablet computer. Search
performance was tested using another tablet (match) or a felt board (mismatch).
WM was assessed. On earlier search trials, WM predicted transfer in both
conditions, and toddlers in the match condition outperformed those in the
mismatch condition; however, the benefit of contextual match and WM decreased
over trials. Contextual match apparently increased proactive interference on
later trials. Findings are interpreted within existing accounts of the transfer
deficit, and a combined account is proposed.
PMID- 28419449
TI - Pharmacogenetic association with neurotoxicity in Hispanic children with acute
lymphoblastic leukaemia.
PMID- 28419450
TI - Acquired blue sclerae in POEMS syndrome.
PMID- 28419451
TI - Do State Continuing Medical Education Requirements for Physicians Improve
Clinical Knowledge?
AB - OBJECTIVE: To evaluate the effect of state continuing medical education (CME)
requirements on physician clinical knowledge. DATA SOURCES: Secondary data for
19,563 general internists who took the Internal Medicine Maintenance of
Certification (MOC) examination between 2006 and 2013. STUDY DESIGN: We took
advantage of a natural experiment resulting from variations in CME requirements
across states over time and applied a difference-in-differences methodology to
measure associations between changes in CME requirements and physician clinical
knowledge. We measured changes in clinical knowledge by comparing initial and MOC
examination performance 10 years apart. We constructed difference-in-differences
estimates by regressing examination performance changes against physician
demographics, county and year fixed effects, trend-state indicators, and state
CME change indicators. DATA COLLECTION: Physician data were compiled by the
American Board of Internal Medicine. State CME policies were compiled from
American Medical Association reports. PRINCIPAL FINDINGS: More rigorous CME
credit-hour requirements (mostly implementing a new requirement) were associated
with an increase in examination performance equivalent to a shift in examination
score from the 50th to 54th percentile. CONCLUSIONS: Among physicians required to
engage in a summative assessment of their clinical knowledge, CME requirements
were associated with an improvement in physician clinical knowledge.
PMID- 28419452
TI - Associations Among Meaning in Life, Body Image, Psychopathology, and Suicide
Ideation in Spanish Participants With Eating Disorders.
AB - OBJECTIVE: The aims of this study were to (a) analyze whether participants with
eating disorders have lower meaning in life than the nonclinical population; (b)
discover whether participants with eating disorders with low meaning in life have
more body image disturbances, more psychopathology, and higher suicide ideation
than participants with high meaning in life; (c) analyze whether meaning in life
is associated with eating disorder psychopathology; and (d) analyze whether
meaning in life is able to predict eating disorder psychopathology and suicide
ideation, when body image is controlled. METHOD: The clinical sample comprised
247 Spanish participants diagnosed with eating disorders, and the nonclinical
sample comprised Spanish 227 participants. RESULTS: Participants with eating
disorders had lower meaning in life than the nonclinical population. Patients
with low meaning in life had higher psychopathology and suicide ideation than
participants with high meaning in life. Meaning in life was a significant
predictor of the eating disorder psychopathology and suicide ideation.
CONCLUSION: Low meaning in life is associated with eating disorder
psychopathology in a Spanish sample with eating disorders.
PMID- 28419453
TI - Obstetrics and gynecology physician knowledge of Rh immune globulin prophylaxis.
AB - BACKGROUND: Previous studies have shown that more than 20% of laboratories would
have recommended inaccurate doses of Rh immune globulin (RhIG) in hypothetical
cases. Efforts have been made in educating laboratories in correct dosing
calculations; however, obstetricians are most often responsible for ordering
RhIG. The objective of this study was to assess knowledge of RhIG indications and
dosing among obstetrics and gynecology (OB/GYN) physicians in the United States.
STUDY DESIGN AND METHODS: An anonymous 17- question online survey was distributed
to all OB/GYN resident and attending physicians affiliated with US residency
training programs. RESULTS: A total of 165 surveys were collected, with 139 fully
completed. Ninety-two percent of respondents correctly recognized the need for
RhIG in D- patients with negative antibody screens. In a scenario of a
fetomaternal hemorrhage (FMH) of 45 mL, only 22% of respondents correctly chose
the appropriate RhIG dosage. Of those who were correct, 10% had correctly
identified 30 mL as the amount of fetal whole blood covered by one dose of RhIG,
while 48% incorrectly identified 15 mL (n = 31). A total of 49.3% of respondents
reported residency as the most recent formal training on RhIG dosing and 35%
reported never (n = 140). CONCLUSIONS: Our study found that OB/GYN physicians are
knowledgeable regarding indications for RhIG immunoprophylaxis but were
insufficient at calculating dosages in cases of FMH. More standardized education
and training among OB/GYN physicians may decrease the risk of maternal
alloimmunization, in part because RhIG dosage recommendations from laboratories
are not standard practice.
PMID- 28419455
TI - Human Electrical Muscular Incapacitation and Effects on QTc Interval.
AB - Human Electrical Muscular Incapacitation (HEMI) is used to subdue combative
individuals. Changes in cardiac electrical activity have been proposed as the
cause of death in a small fraction of these individuals. The current study sought
to determine whether changes in QTc interval occur after HEMI exposure. Twenty
four participants had EKG readings before a 5-second HEMI exposure and within 30
min after exposure. All subject EKGs were read by a data-blinded cardiac
electrophysiologist who calculated a QT corrected (QTc) interval. QTc interval
was calculated using Bazett method. QTc prolongation was defined as >430 ms and a
threshold of 30 ms for identifying QTc lengthening. Five participants experienced
QTc prolongation and six had QTc lengthening. One participant developed QTc
prolongation exceeding 500 ms, which carries a risk of developing multifocal
ventricular tachycardia. These results suggest that HEMI exposure may cause EKG
changes with a risk of ventricular tachycardia.
PMID- 28419454
TI - The de novo autism spectrum disorder RELN R2290C mutation reduces Reelin
secretion and increases protein disulfide isomerase expression.
AB - Despite the recent identification of over 40 missense heterozygous Reelin gene
(RELN) mutations in autism spectrum disorder (ASD), none of these has been
functionally characterized. Reelin is an integral signaling ligand for proper
brain development and post-natal synapse function - properties likely disrupted
in ASD patients. We find that the R2290C mutation, which arose de novo in an
affected ASD proband, and other analogous mutations in arginine-amino acid
arginine domains reduce protein secretion. Closer analysis of RELN R2290C
heterozygous neurospheres reveals up-regulation of Protein Disulfide Isomerase
A1, best known as an endoplasmic reticulum-chaperone protein, which has been
linked to neuronal pathology. This effect is recapitulated in a heterozygous RELN
mouse mutant that is characterized by defective Reelin secretion. These findings
suggest that both a deficiency in Reelin signaling and pathologic impairment of
Reelin secretion may contribute to ASD risk.
PMID- 28419456
TI - Time-lapse lab-based x-ray nano-CT study of corrosion damage.
AB - An experimental protocol (workflow) has been developed for time-lapse x-ray
nanotomography (nano-CT) imaging of environmentally driven morphological changes
to materials. Two case studies are presented. First, the leaching of nanoparticle
corrosion inhibitor pigment from a polymer coating was followed over 14 days,
while in the second case the corrosion damage to an AA2099 aluminium alloy was
imaged over 12 hours. The protocol includes several novel aspects relevant to
nano-CT with the use of a combination of x-ray absorption and phase contrast data
to provide enhanced morphological and composition information, and hence reveal
the best information to provide new insights into the changes of different phases
over time. For the pigmented polymer coating containing nominally strontium
aluminium polyphosphate, the strontium-rich components within the materials are
observed to leach extensively whereas the aluminium-rich components are more
resistant to dissolution. In the case of AA2099 it is found that the initial
grain boundary corrosion is driven by the presence of copper-rich phases and is
then followed by the corrosion of grains of specific orientation.
PMID- 28419457
TI - Subscales of the Barratt Impulsiveness Scale differentially relate to the Big
Five factors of personality.
AB - The place of impulsiveness in multidimensional personality frameworks is still
unclear. In particular, no consensus has yet been reached with regard to the
relation of impulsiveness to Neuroticism and Extraversion. We aim to contribute
to a clearer understanding of these relationships by accounting for the
multidimensional structure of impulsiveness. In three independent studies, we
related the subscales of the Barratt Impulsiveness Scale (BIS) to the Big Five
factors of personality. Study 1 investigated the associations between the BIS
subscales and the Big Five factors as measured by the NEO Five-Factor Inventory
(NEO-FFI) in a student sample (N = 113). Selective positive correlations emerged
between motor impulsiveness and Extraversion and between attentional
impulsiveness and Neuroticism. This pattern of results was replicated in Study 2
(N = 132) using a 10-item short version of the Big Five Inventory. In Study 3, we
analyzed BIS and NEO-FFI data obtained from a sample of patients with
pathological buying (N = 68). In these patients, the relationship between motor
impulsiveness and Extraversion was significantly weakened when compared to the
non-clinical samples. At the same time, the relationship between attentional
impulsiveness and Neuroticism was substantially stronger in the clinical sample.
Our studies highlight the utility of the BIS subscales for clarifying the
relationship between impulsiveness and the Big Five personality factors. We
conclude that impulsiveness might occupy multiple places in multidimensional
personality frameworks, which need to be specified to improve the
interpretability of impulsiveness scales.
PMID- 28419458
TI - Therapeutic potential of novel formulated forms of curcumin in the treatment of
breast cancer by the targeting of cellular and physiological dysregulated
pathways.
AB - Breast cancer is among the most important causes of cancer related death in
women. There is a need for novel agents for targeting key signaling pathways to
either improve the efficacy of the current therapy, or reduce toxicity. There is
some evidence that curcumin may have antitumor activity in breast cancer. Several
clinical trials have investigated its activity in patients with breast cancer,
including a recent trial in breast cancer patients receiving radiotherapy, in
whom it was shown that curcumin reduced the severity of radiation dermatitis,
although it is associated with low bioavailability. Several approaches have been
developed to increase its absorption rate (e.g., nano crystals, liposomes,
polymers, and micelles) and co-delivery of curcumin with adjuvants as well as
different conjugation to enhance its bioavailability. In particular, micro
emulsions is an option for transdermal curcumin delivery, which has been reported
to increase its absorption. Lipid-based nano-micelles is another approach to
enhance curcumin absorption via gastrointestinal tract, while polymer-based nano
formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of
curcumin at a sustained level. This review summarizes the current data of the
therapeutic potential of novel formulations of curcumin with particular emphasis
on recent preclinical and clinical studies in the treatment of breast cancer.
PMID- 28419459
TI - How can we restrict the sale of sports and energy drinks to children? A proposal
for a World Health Organization-sponsored framework convention to restrict the
sale of sports and energy drinks.
AB - High-sugar drinks, including fruit drinks, soft drinks, sports drinks and energy
drinks, are of no nutritional value and contribute to the burden of dental
disease in all age groups. The manufacturers of sports and energy drinks have
elected to target children in their marketing campaigns and promote a misleading
association between their products, healthy lifestyles and sporting prowess. The
World Health Organization (WHO) has acknowledged that strategies aimed at
prevention of dental disease are the only economically viable options for
managing the oral health of children in low- and middle-income countries.
Developed nations will also be advantaged by preventive programmes given that the
cost of providing dental care to those who cannot pay draws valuable resources
away from more pressing health issues. The Convention on the Rights of the Child
(CRC) obligates governments to develop legislation to protect the health of
children. A framework convention modelled on the existing Framework Convention
for Tobacco Control, supported by the WHO, would assist governments to
proactively legislate to restrict the sale of sports and energy drinks to
children. This article will consider how a framework convention would be an
advantage with reference to the strategies used by sports and energy drink
manufacturers in Australia.
PMID- 28419460
TI - Land plants drive photorespiration as higher electron-sink: comparative study of
post-illumination transient O2 -uptake rates from liverworts to angiosperms
through ferns and gymnosperms.
AB - In higher plants, the electron-sink capacity of photorespiration contributes to
alleviation of photoinhibition by dissipating excess energy under conditions when
photosynthesis is limited. We addressed the question at which point in the
evolution of photosynthetic organisms photorespiration began to function as
electron sink and replaced the flavodiiron proteins which catalyze the reduction
of O2 at photosystem I in cyanobacteria. Algae do not have a higher activity of
photorespiration when CO2 assimilation is limited, and it can therefore not act
as an electron sink. Using land plants (liverworts, ferns, gymnosperms, and
angiosperms) we compared photorespiration activity and estimated the electron
flux driven by photorespiration to evaluate its electron-sink capacity at CO2
compensation point. In vivo photorespiration activity was estimated by the
simultaneous measurement of O2 -exchange rate and chlorophyll fluorescence yield.
All C3-plants leaves showed transient O2 -uptake after actinic light illumination
(post-illumination transient O2 -uptake), which reflects photorespiration
activity. Post-illumination transient O2 -uptake rates increased in the order
from liverworts to angiosperms through ferns and gymnosperms. Furthermore,
photorespiration-dependent electron flux in photosynthetic linear electron flow
was estimated from post-illumination transient O2 -uptake rate and compared with
the electron flux in photosynthetic linear electron flow in order to evaluate the
electron-sink capacity of photorespiration. The electron-sink capacity at the CO2
-compensation point also increased in the above order. In gymnosperms
photorespiration was determined to be the main electron-sink. C3-C4 intermediate
species of Flaveria plants showed photorespiration activity, which intermediate
between that of C3- and C4-flaveria species. These results indicate that in the
first land plants, liverworts, photorespiration started to function as electron
sink. According to our hypothesis, the dramatic increase in partial pressure of
O2 in the atmosphere about 0.4 billion years ago made it possible to drive
photorespiration with higher activity in liverworts.
PMID- 28419461
TI - Assent in Pediatric Patients.
AB - AIM: To report an analysis of the concept of pediatric assent. BACKGROUND: The
concept of assent is poorly defined in current literature which may lead to
potentially flawed practices in obtaining pediatric assent. DESIGN: The Walker
and Avant (2011) method is used to provide clarity to the concept of pediatric
assent. DATA SOURCES: Data were collected from PubMed, Academic Search Premier,
PhilPapers, Wikipedia, and Google. REVIEW METHODS: Data were collected from 2014
to 2015. Twenty-three sources published between 2011 and 2015, nine sources
published between 2003 and 2009, the Belmont Report (1979), and the American
Academy of Pediatrics' report (1995) were included for pertinent contributions to
this multidisciplinary concept analysis. RESULTS: Elements of assent include a
patient's thoughtful review of the proposed treatment and rational decision in
choosing the best course of action. There may be social, familial, and cognitive
development factors influencing this process. CONCLUSION: This framework uses
nurses' knowledge of cognitive development and ethics to inform practice. Assent
is respectful of minor patients and ensures their rights are protected. Policies
and procedures can be developed to incorporate assent, researchers have a
stronger conceptual base, and educators can train nurses to help pediatric
patients develop medical decision making skills.
PMID- 28419462
TI - Modeling and Simulation of Pivotal Clinical Trials Using Linked Models for
Multiple Endpoints in Chronic Obstructive Pulmonary Disease With Roflumilast.
AB - Roflumilast is a selective phosphodiesterase 4 inhibitor (PDE4i) for the
treatment of severe chronic obstructive pulmonary disease (COPD). In 2 large
phase 3 trials in a broader population of COPD patients (BY217/M2-111,
ClinicalTrials.gov: NCT00076089 and BY217/M2-112, ClinicalTrials.gov:
NCT00430729), treatment with roflumilast reduced the rate of exacerbations;
however, the reduction did not reach statistical significance. Two linked dose
response models for the primary (annualized COPD exacerbation counts) and
secondary (change from baseline in forced expiratory volume in 1 second [FEV1 ])
end points were therefore developed to characterize and quantify effect sizes and
the patient characteristics influencing them. The models showed that disease
severity and bronchitis, particularly the severity of bronchitis expressed in
cough-and-sputum scores, were good predictors of exacerbation rates and
differential benefit of roflumilast in exacerbation reduction. The models were
used to support the rational design of 2 phase 3 randomized, placebo-controlled
clinical trials (BY217/M2-124, ClinicalTrials.gov: NCT00297102 and BY217/M2-125,
ClinicalTrials.gov: NCT00297115) by identifying the most appropriate patient
population using clinical trial simulations. Model predictions for both end
points were found to be highly accurate - as confirmed by the results from these
trials, which led to the approval of roflumilast as the first oral PDE4i for the
treatment of COPD in patients associated with chronic bronchitis and a history of
exacerbations.
PMID- 28419463
TI - Profiling of anthocyanins in transgenic purple-fleshed sweet potatoes by HPLC
MS/MS.
AB - BACKGROUND: Anthocyanins in purple-fleshed sweet potato (PSP) are beneficial to
human health. The leaf color (Lc) gene is a transcription factor involved in
regulating anthocyanin biosynthesis. The anthocyanin profiles of wild-type PSP of
Ayamurasaki and its three Lc-transgenic lines were investigated by high
performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). In vitro
antioxidant activities of wild-type and Lc-transgenic lines, including reducing
power activity, DPPH radical scavenging activity, hydroxyl radical scavenging
activity, linoleic acid autoxidation inhibition activity, ABTS free radical
scavenging activity and oxygen radical absorbance capacity activity, were
measured. RESULTS: The results showed that the total anthocyanin contents
increased 1.5-1.9 times in three transgenic lines compared with that in wild-type
PSP. Seventeen anthocyanins were found in wild-type PSP, while 19 in Lc
transgenic lines including cyanidin-based, peonidin-based and pelargonidin-based
anthocyanins. Three pelargonidin-based anthocyanins were detected in three Lc
transgenic lines. Among them, the relative contents of cyanidin-based and
pelargonidin-based anthocyanins increased 1.9-2.0 and 3.4-4.5 times respectively,
while peonidin-based anthocyanins decreased 1.8-1.9 times in Lc-transgenic lines,
compared with wild-type PSP. PSP from wild-type Ayamurasaki and three Lc
transgenic lines exhibited potent antioxidant activities, whereas there was no
distinct difference among them. CONCLUSION: The transgene Lc significantly
increased the content of total anthocyanins and remarkably changed the
anthocyanin profiles in Ayamurasaki. Such novel and high content of anthocyanins
obtained in the Lc-transgenic lines with potent antioxidant activities may
provide unique functional products with potential helpful for human health. (c)
2017 Society of Chemical Industry.
PMID- 28419464
TI - A new species of Chrysobrycon (Characiformes, Characidae, Stevardiinae) from the
Amazon River basin in Colombia, with a new diagnostic characteristic for the
genus.
AB - Chrysobrycon mojicai sp. nov. is described from forest streams that are part of
the Amazon River basin in Colombia. It is distinguished from all congeners by
having most of the maxillary teeth with distal tips lateroventrally curved (v.
teeth straight along their lengths) and a greater number of dentary teeth (20-27
v. 11-19, except in Chrysobrycon yoliae). The posterior margin of the ventral
process of the quadrate does not reach the vertical through the posterior margin
of the symplectic and these features differentiate C. mojicai from Chrysobrycon
myersi and C. yoliae (v. posterior margin of ventral process of quadrate reaching
vertical through posterior margin of symplectic). In species of Chrysobrycon, the
frontals are extensively contacting each other along the midline, resulting in an
absent frontal fontanel and a reduced parietal fontanel. This extensive contact
between the frontals modifying the fontanels is a condition rarely found within
the Stevardiinae and hence is proposed as an additional diagnostic characteristic
for the genus. An updated identification key for all Chrysobrycon species is
provided.
PMID- 28419465
TI - Assessing PTSD in the military: Validation of a scale distributed to Danish
soldiers after deployment since 1998.
AB - Since 1998, soldiers deployed to war zones with the Danish Defense (~31,000) have
been invited to fill out a questionnaire on post-mission reactions. This provides
a unique data source for studying the psychological toll of war. Here, we
validate a measure of PTSD-symptoms from the questionnaire. Soldiers from two
cohorts deployed to Afghanistan with the International Security Assistance Force
(ISAF) in 2009 (ISAF7, N = 334) and 2013 (ISAF15, N = 278) filled out a standard
questionnaire (Psychological Reactions following International Missions, PRIM)
concerning a range of post-deployment reactions including symptoms of PTSD (PRIM
PTSD). They also filled out a validated measure of PTSD-symptoms in DSM-IV, the
PTSD-checklist (PCL). We tested reliability of PRIM-PTSD by estimating Cronbach's
alpha, and tested validity by correlating items, clusters, and overall scale with
corresponding items in the PCL. Furthermore, we conducted two confirmatory factor
analytic models to test the factor structure of PRIM-PTSD, and tested measurement
invariance of the selected model. Finally, we established a screening and a
clinical cutoff score by application of ROC analysis. We found high internal
consistency of the PRIM-PTSD (Cronbach's alpha = 0.88; both cohorts), strong item
item (0.48-0.83), item-cluster (0.43-0.72), cluster-cluster (0.71-0.82) and full
scale (0.86-0.88) correlations between PRIM-PTSD and PCL. The factor analyses
showed adequate fit of a one-factor model, which was also found to display strong
measurement invariance across cohorts. ROC curve analysis established cutoff
scores for screening (sensitivity = 1, specificity = 0.93) and clinical use
(sensitivity = 0.71, specificity = 0.98). In conclusion, we find that PRIM-PTSD
is a valid measure for assessing PTSD-symptoms in Danish soldiers following
deployment.
PMID- 28419466
TI - The 2016 revised World Health Organization definition of 'myelodysplastic
syndrome with isolated del(5q)'; prognostic implications of single versus double
cytogenetic abnormalities.
AB - The definition of the myelodysplastic syndrome (MDS) subtype 'MDS with isolated
del(5q)' was expanded to include cases with one additional non-chromosome 7 based
cytogenetic abnormality in the 2016 revised World Health Organization
classification. This study applied the revised definition to a large primary MDS
cohort, and evaluated the prognostic impact of the additional cytogenetic
abnormality. Seventy-two of 1067 patients (7%) met the 'MDS with isolated
del(5q)' criteria, 11 (1%) of whom had an additional cytogenetic abnormality.
There was no survival difference between patients in whom del(5q) occurred alone,
compared to those with one additional cytogenetic abnormality (P = 0.52).
PMID- 28419467
TI - Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and
Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials.
AB - Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in
development for heart failure. Phase I trials were suspended when two cimaglermin
alfa-treated subjects experienced concomitant elevations in serum
aminotransferases and total bilirubin, meeting current US Food and Drug
Administration criteria for a serious liver safety signal (i.e., "Hy's Law"). We
assayed mechanistic biomarkers in archived clinical trial serum samples which
confirmed the hepatic origin of the aminotransferase elevations in these two
subjects and identified apoptosis as the major mode of hepatocyte death. Using a
mathematical model of drug-induced liver injury (DILIsym) and a simulated
population, we estimated that the maximum hepatocyte loss in these two subjects
was <13%, which would not result in liver dysfunction sufficient to significantly
increase serum bilirubin levels. We conclude that the two subjects should not be
considered Hy's Law cases and that mechanistic biomarkers and modeling can aid in
refining liver safety risk assessment in clinical trials.
PMID- 28419468
TI - Activation of the Akt-CREB signalling axis by a proline-rich heptapeptide confers
resistance to stress-induced cell death and inflammation.
AB - Cell stress of various kinds can lead to the induction of cell death and a
damaging inflammatory response. Hence, a goal of therapeutic cell-stress
management is to develop agents that might effectively regulate undesirable cell
death and inflammation. To that end, we developed a synthetic peptide of seven
amino acids based on structural mimicry to a functional domain of p53, a key
factor in the responses of cells to stressful stimuli. This heptapeptide, which
we term Stressin-1, was found to inhibit both cell death and the secretion of
inflammatory mediators by various cell types in response to different stressful
agents in vitro. The combined anti-inflammatory and anti-apoptotic activities of
Stressin-1 were associated with a cellular signalling cascade that induced
activation of Akt kinase and activation of the cAMP response element-binding
protein (CREB) transcription factor. These immediate signalling events led to the
inhibition of the signal transducer and activator of transcription and nuclear
factor-kappaB pathways 24 hr later. Unexpectedly, we found no evidence for a
direct involvement of p53 in the effects produced by Stressin-1. Intraperitoneal
administration of 100 MUg of Stressin-1 to lethally irradiated mice significantly
protected them from death. These findings show that activating the Akt-CREB axis
with Stressin-1 can counteract some of the undesirable effects of various cell
stresses. Stressin-1 may have clinical usefulness.
PMID- 28419469
TI - The endoplasmic reticulum-associated protein, OS-9, behaves as a lectin in
targeting the immature calcium-sensing receptor.
AB - The mechanisms responsible for the processing and quality control of the calcium
sensing receptor (CaSR) in the endoplasmic reticulum (ER) are largely unknown. In
a yeast two-hybrid screen of the CaSR C-terminal tail (residues 865-1078), we
identified osteosarcoma-9 (OS-9) protein as a binding partner. OS-9 is an ER
resident lectin that targets misfolded glycoproteins to the ER-associated
degradation (ERAD) pathway through recognition of specific N-glycans by its
mannose-6-phosphate receptor homology (MRH) domain. We show by confocal
microscopy that the CaSR and OS-9 co-localize in the ER in COS-1 cells. In
immunoprecipitation studies with co-expressed OS-9 and CaSR, OS-9 specifically
bound the immature form of wild-type CaSR in the ER. OS-9 also bound the immature
forms of a CaSR C-terminal deletion mutant and a C677A mutant that remains
trapped in the ER, although binding to neither mutant was favored over wild-type
receptor. OS-9 binding to immature CaSR required the MRH domain of OS-9
indicating that OS-9 acts as a lectin most likely to target misfolded CaSR to
ERAD. Our results also identify two distinct binding interactions between OS-9
and the CaSR, one involving both C-terminal domains of the two proteins and the
other involving both N-terminal domains. This suggests the possibility of more
than one functional interaction between OS-9 and the CaSR. When we investigated
the functional consequences of altered OS-9 expression, neither knockdown nor
overexpression of OS-9 was found to have a significant effect on CaSR cell
surface expression or CaSR-mediated ERK1/2 phosphorylation.
PMID- 28419470
TI - Excessive heat-associated gingival necrosis: a case report.
AB - Heat-delivery devices have been associated with relatively high temperatures.
Previous basic research studies suggest that the risk for periodontal tissues is
negligible, as the presence of the root filling materials, amongst other factors,
reduce the risk of overheating. This report describes the case of a 45 year old
male, who was undergoing restorative treatment in a multi-specialty dental
practice. As part of his overall treatment planning, orthograde root canal
retreatment for his maxillary left incisor teeth was deemed necessary, due to
chronic apical periodontitis. Following cold lateral compaction, the coronal
portion of the core material was severed using a System B Heat Source (Kerr
Dental, Orange, CA, USA), with the patient reporting pain as well as a burning
sensation. The following day the patient was seen by a periodontist and gingival
necrosis in relation to the central incisor was found. The most likely cause of
the complication was considered to be excessive heat during the operative
procedure. The patient was followed up for a 2-year period and the soft tissues
returned to their original condition without the need for periodontal treatment.
PMID- 28419471
TI - Spectral analysis of the stick-slip phenomenon in "oral" tribological texture
evaluation.
AB - : "Oral" tribology has become a new paradigm in food texture studies to
understand complex texture attributes, such as creaminess, oiliness, and
astringency, which could not be successfully characterized by traditional texture
analysis nor by rheology. Stick-slip effects resulting from intermittent sliding
motion during kinetic friction of oral mucosa could constitute an additional
determining factor of sensory perception where traditional friction coefficient
values and their Stribeck regimes fail in predicting different lubricant (food
bolus and saliva) behaviors. It was hypothesized that the observed jagged
behavior of most sliding force curves are due to stick-slip effects and depend on
test velocity, normal load, surface roughness as well as lubricant type.
Therefore, different measurement set-ups were investigated: sliding velocities
from 0.01 to 40 mm/s, loads of 0.5 and 2.5 N as well as a smooth and a textured
silicone contact surface. Moreover, dry contact measurements were compared to
model food systems, such as water, oil, and oil-in-water emulsions. Spectral
analysis permitted to extract the distribution of stick-slip magnitudes for
specific wave numbers, characterizing the occurrence of jagged force peaks per
unit sliding distance, similar to frequencies per unit time. The spectral
features were affected by all the above mentioned tested factors. Stick-slip
created vibration frequencies in the range of those detected by oral
mechanoreceptors (0.3-400 Hz). The study thus provides a new insight into the use
of tribology in food psychophysics. PRACTICAL APPLICATIONS: Dynamic spectral
analysis has been applied for the first time to the force-displacement curves in
"oral" tribology. Analyzing the stick-slip phenomenon in the dynamic friction
provides new information that is generally overlooked or confused with machine
noise and which may help to understand friction-related sensory attributes. This
approach allows us to differentiate samples that have similar friction
coefficient, but are perceived differently in the mouth. The next step of our
research will be to combine spectral attributes, such as the magnitudes of
specific wave number bands and possibly their evolution during sliding, together
with friction coefficient and viscosity values of foods with sensory results. The
highest potential lies in predicting smoothness in opposition to roughness of a
surface, such as a rough tongue when eating astringent or dry foods, or of
particles when eating grainy foods. The effects of food ingredients at the nano
to macroscales can then be used to optimize a specific lubrication behavior.
PMID- 28419472
TI - Hepatic expression of oncogenes Bmi1 and Dkk1 is up-regulated in hepatitis B
virus surface antigen-transgenic mice and can be induced by treatment with HBV
particles or lipopolysaccharides in vitro.
AB - Previous studies have shown that hepatocellular carcinoma (HCC) develops more
frequently in hepatitis B virus surface antigen (HBsAg)-transgenic mice (Alb/HBs)
than in wild-type (WT) mice. However, the mechanism of this HCC model has not
been well documented. Toll-like receptor 4 (Tlr4) signaling probably links innate
immunity and HCC progression. This study was designed to investigate the role of
innate immunity in hepatocarcinogenesis in Alb/HBs mice. Immunohistochemical
analysis of liver specimens from Alb/HBs mice (16 per group) showed that the
oncogenes Bmi1 (16/16, 100%) and Dkk1 (13/16, 81.25%) were highly expressed in
Alb/HBs mice, whereas the other oncogenes evaluated were expressed in smaller
percentages of mice (Afp, 9/16, 56.2%; Ctnnb1, 5/16, 31.3%; Epcam, 0/16; 0%).
Comparable results were obtained by quantitative PCR analysis. Hepatic gene
expression of Tlr2, Tlr4, Il6 and Tnf was additionally elevated in Alb/HBs mice.
Stimulation of primary murine hepatocytes with cell culture-derived HBV particles
or LPS increased the expression of oncogenes (Bmi1, Dkk1) and inflammatory
factors (Tnf, Il6, Tlr4). Proliferation and colony formation of hepatoma cells
were enhanced by treatment with HBV and LPS and were impaired by the suppression
of Bmi1 and Dkk1 by small interfering RNAs. Substantial induction of BMI1 and
DKK1 was found in liver biopsy samples from patients with HBV-related HCC but not
in HCC samples without HBV infection background. These findings suggest that
innate immunity may link inflammation and tumor progression during chronic HBV
infection, involving the oncogenes BMI1 and DKK1.
PMID- 28419474
TI - Using Advances From Cognitive Behavioral Models of Anxiety to Guide Treatment for
Social Anxiety Disorder.
AB - This case features an adult male with moderate social anxiety disorder and mild
depressive symptoms who showed an initial positive response to an earlier
experience of cognitive behavior therapy, but then relapsed when he started
avoiding social situations again because of continuing beliefs that experiencing
anxiety was unacceptable. His treatment at our clinic focused on shifting
unhelpful thinking about the likelihood and consequences of becoming anxious and
reengaging in avoided social situations so he could learn to tolerate negative
affect and uncertainty. The treatment approach draws from cognitive behavioral
models of social anxiety and highlights advances in clinical science, especially
recent work on the causal role of interpretation biases (the tendency to assign
negative or threatening meaning to ambiguous situations) in the maintenance and
reduction of anxiety.
PMID- 28419473
TI - Translating the Cognitive Model of PTSD to the Treatment of Very Young Children:
A Single Case Study of an 8-Year-Old Motor Vehicle Accident Survivor.
AB - Posttraumatic stress disorder (PTSD) is a clinical condition that occurs after a
discrete traumatic event, such as an accident or assault. Research into PTSD has
primarily been adult-focused; however, there is a growing body of evidence
evaluating the theory and treatment of PTSD in young children. Consequently,
cognitive behavior therapy (CBT) interventions for PTSD in youth have been
developed that focus on 3 core components of the cognitive model-a disorganized
memory of the trauma, maladaptive appraisals of the trauma and its effects
(meanings), and dysfunctional coping mechanisms (management). Here, we describe
the extension of this treatment approach (termed CBT-3M) to very young children
(3-8 years) through the case of Dylan, an 8-year-old motor vehicle accident
survivor. This serves as an illustration of the underlying theory and its
successful application. Further work is intended to provide evidence of the
efficacy of this treatment via an ongoing treatment trial.
PMID- 28419475
TI - Fruit and vegetable intake and prostate cancer risk in the European Prospective
Investigation into Cancer and Nutrition (EPIC).
AB - Several dietary factors have been studied in relation to prostate cancer;
however, most studies have not reported on subtypes of fruit and vegetables or
tumor characteristics, and results obtained so far are inconclusive. This study
aimed to examine the prospective association of total and subtypes of fruit and
vegetable intake with the incidence of prostate cancer overall, by grade and
stage of disease, and prostate cancer death. Lifestyle information for 142,239
men participating in the European Prospective Investigation into Cancer and
Nutrition from 8 European countries was collected at baseline. Multivariable Cox
regression models were used to estimate hazard ratios (HRs) and 95% confidence
intervals (CIs). After an average follow-up time of 13.9 years, 7,036 prostate
cancer cases were identified. Compared with the lowest fifth, those in the
highest fifth of total fruit intake had a significantly reduced prostate cancer
risk (HR = 0.91; 95% CI = 0.83-0.99; p-trend = 0.01). No associations between
fruit subtypes and prostate cancer risk were observed, except for citrus fruits,
where a significant trend was found (HR = 0.94; 95% CI = 0.86-1.02; p-trend =
0.01). No associations between total and subtypes of vegetables and prostate
cancer risk were observed. We found no evidence of heterogeneity in these
associations by tumor grade and stage, with the exception of significant
heterogeneity by tumor grade (pheterogeneity <0.001) for leafy vegetables. No
significant associations with prostate cancer death were observed. The main
finding of this prospective study was that a higher fruit intake was associated
with a small reduction in prostate cancer risk. Whether this association is
causal remains unclear.
PMID- 28419477
TI - The effectiveness of riboflavin and ultraviolet light pathogen reduction
technology in eliminating Trypanosoma cruzi from leukoreduced whole blood.
AB - BACKGROUND: The parasitic Chagas disease is caused by the protozoan Trypanosoma
cruzi, which is mainly transmitted by insect vectors. Other infection routes,
both in endemic and in nonendemic areas, include organ and marrow
transplantation, congenital transmission, and blood transfusion. Asymptomatic
chronic chagasic individuals may have a low and transient parasitemia in
peripheral blood and, consequently, they can unknowingly transmit the disease via
blood transfusion. Riboflavin and ultraviolet (UV) light pathogen reduction is a
method to reduce pathogen transfusion transmission risk based on damage to the
pathogen nucleic acids. STUDY DESIGN AND METHODS: In this study, we tested the
effectiveness of this technology for the elimination of T. cruzi parasites in
artificially contaminated whole blood units (WBUs) and thus for decreasing the
risk of T. cruzi transfusion transmission. The contaminated WBUs were
leukoreduced by filtration and treated with riboflavin and UV light. The level of
pathogen reduction was quantified by a real-time polymerase chain reaction (qPCR)
and a real-time reverse transcription-polymerase chain reaction (RT-qPCR) as a
viability assay. RESULTS: The RNA (cDNA) quantification of the parasites showed a
more than 99% reduction of viable T. cruzi parasites after leukoreduction and a
complete reduction (100%) after the riboflavin and UV light treatment.
CONCLUSION: Riboflavin and UV light treatment and leukoreduction used in
conjunction appears to eliminate significant amounts of viable T. cruzi in whole
blood. Both strategies could complement other blood bank measures already
implemented to prevent the transmission of T. cruzi via blood transfusion.
PMID- 28419478
TI - Exposure to the American flag polarizes democratic-republican ideologies.
AB - Some prior research has suggested that exposure to the American flag tilts
Americans towards Republicanism, while others have proffered that it brings outs
a common 'together' perspective instead. We explore a third possibility - that it
may actually polarize Americans' political ideology. It is generally accepted
that exposure to an environmental cue can shift attitudes and behaviours, at
least partly or temporarily, in a manner that is consistent with that cue. Yet,
the same cue can mean different things to different people. In the same vein,
given how national identity and political ideology are intertwined in the United
States, we hypothesize that the American flag should heighten different political
beliefs depending on individuals' political ideology. To Democrats, being
American is to support Democratic values, but to Republicans, being American is
to support Republican values. The American flag thus should heighten Democrats of
their Democratic identity, and it should heighten Republicans of their Republican
one. The results of an experiment with 752 American respondents who were
representative of the US population supported this polarizing effect of the
American flag. The theoretical and policy implications of the findings are
offered.
PMID- 28419476
TI - Cortactin, a Lyn substrate, is a checkpoint molecule at the intersection of BCR
and CXCR4 signalling pathway in chronic lymphocytic leukaemia cells.
AB - Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an
actin cytoskeletal regulatory role involved in cell migration and cancer
progression following its phosphorylation at Y421. We recently demonstrated that
Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL).
This work was aimed at defining the functional role of Cortactin in these
patients. We found that Cortactin is variably expressed in CLL patients both in
the peripheral blood and lymph nodes and that its expression correlates with the
release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic
cells. Cortactin knockdown, by siRNA, induced a reduction in MMP-9 release as
well as a decrease of migration capability of leukaemic B cells in vitro, also
after chemotactic stimulus. Furthermore, Cortactin phosphorylation was lowered by
the Src kinase-inhibitor PP2 with a consequent decrease of MMP-9 release in
culture medium. An impaired migration, as compared to control experiments without
Cortactin knockdown, was observed following CXCL12 triggering. Reduced Cortactin
expression and phosphorylation were also detected both in vivo and in vitro after
treatment with Ibrutinib, a Btk inhibitor. Our results highlight the role of
Cortactin in CLL as a check-point molecule between the BCR and CXCR4 signalling
pathways.
PMID- 28419479
TI - Sonographic diagnosis of a radiographically occult displaced fracture of a costal
cartilage.
AB - We report the case of a 22-year-old athlete who sustained a blunt thoracic trauma
to the right chest causing a costal cartilage fracture. Plain radiographs
revealed no abnormalities while sonographic (US) examination performed a week
later because of persistent pain led to the diagnosis of a displaced fracture of
the right tenth costal cartilage. A follow-up US examination confirmed the
healing of the fracture and allowed the patient to return to competitive sport
activity. We recommend the use of US in patients with persisting pain after
thoracic trauma with negative plain radiographs of the ribs to rule out
radiographically occult costal cartilage fractures. (c) 2017 Wiley Periodicals,
Inc. J Clin Ultrasound 45:605-607, 2017.
PMID- 28419480
TI - Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib
Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and
Simulation Approach.
AB - Neutropenia is the most commonly reported hematologic toxicity following
treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for
metastatic breast cancer. Using data from 185 advanced cancer patients receiving
palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was
developed to describe the time course of absolute neutrophil count (ANC) and
quantify the exposure-response relationship for neutropenia. These analyses help
in understanding neutropenia associated with palbociclib and its comparison with
chemotherapy-induced neutropenia. In the model, palbociclib plasma concentration
was related to its antiproliferative effect on precursor cells through drug
related parameters (ie, maximum estimated drug effect and concentration
corresponding to 50% of the maximum effect), and neutrophil physiology was
mimicked through system-related parameters (ie, mean transit time, baseline ANC,
and feedback parameter). Sex and baseline albumin level were significant
covariates for baseline ANC. It was demonstrated by different model evaluation
approaches (eg, prediction-corrected visual predictive check and standardized
visual predictive check) that the final model adequately described longitudinal
ANC with good predictive capability. The established model suggested that higher
palbociclib exposure was associated with lower longitudinal neutrophil counts.
The ANC nadir was reached approximately 21 days after palbociclib treatment
initiation. Consistent with their mechanisms of action, neutropenia associated
with palbociclib (cytostatic) was rapidly reversible and noncumulative, with a
notably weaker antiproliferative effect on precursor cells relative to
chemotherapies (cytotoxic). This pharmacokinetic-pharmacodynamic model aids in
predicting neutropenia and optimizing dosing for future palbociclib trials with
different dosing regimen combinations.
PMID- 28419481
TI - Are induced fit protein conformational changes caused by ligand-binding
predictable? A molecular dynamics investigation.
AB - In this work, the ability of molecular dynamics simulations (MD) to prospectively
predict regions of ligand binding sites that could undergo induced fit effects
was investigated. Conventional MD was run on 39 apo structures (no ligand), and
the resulting trajectories were compared to a set of 147 holo X-ray structures
(ligand-bound). It was observed from the simulations, in the absence of the
ligands, that structures exhibiting large residue conformational changes
indicated higher likelihood of induced fit effects. Nevertheless, the simulation
results did not perform better than using the normalized crystallographic
structural factors as predictors of active-site rigid residues (87% predictive
power) and mobile residues (47% predictive power). While the simulations could
not produce full active sites conformations similar to holo-like states, it was
found that the simulations could reproduce bound state conformations of
individual residues. These results suggest potential issues in the use of
unligated simulation frames directly for drug design applications such as ligand
docking, and an overall caution in the use of protein flexibility in docking
protocols should be emphasized. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419482
TI - FMEA of manual and automated methods for commissioning a radiotherapy treatment
planning system.
AB - PURPOSE: To evaluate the level of risk involved in treatment planning system
(TPS) commissioning using a manual test procedure, and to compare the associated
process-based risk to that of an automated commissioning process (ACP) by
performing an in-depth failure modes and effects analysis (FMEA). METHODS: The
authors collaborated to determine the potential failure modes of the TPS
commissioning process using (a) approaches involving manual data measurement,
modeling, and validation tests and (b) an automated process utilizing application
programming interface (API) scripting, preloaded, and premodeled standard
radiation beam data, digital heterogeneous phantom, and an automated
commissioning test suite (ACTS). The severity (S), occurrence (O), and
detectability (D) were scored for each failure mode and the risk priority numbers
(RPN) were derived based on TG-100 scale. Failure modes were then analyzed and
ranked based on RPN. The total number of failure modes, RPN scores and the top 10
failure modes with highest risk were described and cross-compared between the two
approaches. RPN reduction analysis is also presented and used as another
quantifiable metric to evaluate the proposed approach. RESULTS: The FMEA of a MTP
resulted in 47 failure modes with an RPNave of 161 and Save of 6.7. The highest
risk process of "Measurement Equipment Selection" resulted in an RPNmax of 640.
The FMEA of an ACP resulted in 36 failure modes with an RPNave of 73 and Save of
6.7. The highest risk process of "EPID Calibration" resulted in an RPNmax of 576.
CONCLUSIONS: An FMEA of treatment planning commissioning tests using automation
and standardization via API scripting, preloaded, and pre-modeled standard beam
data, and digital phantoms suggests that errors and risks may be reduced through
the use of an ACP.
PMID- 28419483
TI - Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill
Multiple-Trauma Patients at the Usual Dosage and a New Proposal for
Administration.
AB - The pharmacokinetic profile of intravenous acetaminophen administered to
critically ill multiple-trauma patients was studied after 4 consecutive doses of
1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60,
90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected
(during 6-hour intervals between doses) to determine serum and urine
acetaminophen concentrations. These were used to calculate the following
pharmacokinetic parameters: maximum and minimum concentrations, terminal half
life, area under serum concentration-time curve from 0 to 6 hours, mean residence
time, volume of distribution, and serum and renal clearance of acetaminophen.
Daily doses of acetaminophen required to obtain steady-state minimum (bolus
dosing) and average plasma concentrations (continuous infusion) of 10 MUg/mL were
calculated (10 MUg/mL is the presumed lower limit of the analgesic range). Data
are expressed as median [interquartile range]. Twenty-two patients were studied,
mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84]
kg). Acetaminophen concentrations and pharmacokinetic parameters were these:
maximum concentration 33.6 [25.7-38.7] MUg/mL and minimum concentration 0.5 [0.2
2.3] MUg/mL, all values below 10 MUg/mL and 8 below the detection limit; half
life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7]
MUg.h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of
distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7]
L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady
state minimum concentration of 10 MUg/mL would be 12.2 [7.8-16.4] g/day (166 [112
202] mg/[kg.day]); for an average steady-state concentration of 10 MUg/mL, they
would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg.day]). In conclusion,
administration of acetaminophen at the recommended dosage of 1 g per 6 hours to
critically ill multiple-trauma patients yields serum concentrations below 10
MUg/mL due to increased elimination. To reach the 10 MUg/mL target, and from a
strictly pharmacokinetic point of view, continuous infusion may be more feasible
than bolus dosing. Such a change in dosing strategy requires appropriate,
pharmacokinetic-pharmacodynamic and specific safety study.
PMID- 28419484
TI - Variations in the functional visual field for detection of lung nodules on chest
computed tomography: Impact of nodule size, distance, and local lung complexity.
AB - PURPOSE: To explore the characteristics that impact lung nodule detection by
peripheral vision when searching for lung nodules on chest CT-scans. METHODS:
This study was approved by the local IRB and is HIPAA compliant. A simulated
primary (1 degrees ) target mass (2 * 2 * 5 cm) was embedded into 5 cm thick
subvolumes (SV) extracted from three unenhanced lung MDCT scans (64 row, 1.25 mm
thickness, 0.7 mm increment). One of 30 solid, secondary nodules with either 3-4
mm and 5-8 mm diameters were embedded into 192 of 207 SVs. The secondary nodule
was placed at a random depth within each SV, a transverse distance of 2.5, 5,
7.5, or 10 mm, and along one of eight rays cast every 45 degrees from the center
of the 1 degrees mass. Video recordings of transverse paging in cranio-caudal
direction were created for each SV (frame rate three sections/sec). Six
radiologists observed each cine-loop once while gaze-tracking hardware assured
that gaze was centered on the 1 degrees mass. Each radiologist assigned a
confidence rating (0-5) to the detection of a secondary nodule and indicated its
location. Detection sensitivity was analyzed relative to secondary nodule size,
transverse distance, radial orientation, and lung complexity. Lung complexity was
characterized by the number of particles (connected pixels) and the sum of the
area of all particles above a -500 HU threshold within regions of interest around
the 1 degrees mass and secondary nodule. RESULTS: Using a proportional odds
logistic regression model and eliminating redundant predictors, models fit
individually to each reader resulted in the following decreasing order of
association based on greatest reduction in Akaike Information Criterion:
secondary nodule diameter (6/6 readers, P < 0.001), distance from central mass
(6/6 readers, P < 0.001), lung complexity particle count (5/6 readers, P = 0.05),
and lung complexity particle area (3/6 readers, P = 0.03). Substantial inter
reader differences in sensitivity to decreasing nodule diameter, distance, and
complexity characteristics were observed. CONCLUSIONS: Of the investigated
parameters, secondary nodule size, distance from the gaze center and lung
complexity (particle number and area) significantly impact nodule detection with
peripheral vision.
PMID- 28419485
TI - Maternal and Child Characteristics Associated With Mother-Child Interaction in
One-Year-Olds.
AB - Mothers' interactions with their young children have predicted later child
development, behavior, and health, but evidence has been developed mainly in at
risk clinical samples. An economically and racially diverse sample of pregnant
women who were not experiencing a high-risk pregnancy were recruited to
participate in a community-based, longitudinal study of factors associated with
child cognitive and social-emotional development during the first 3 years. The
purpose of the present analysis was to identify associations between the
characteristics of 1125 mothers and their 1-year-olds and the mothers' and
children's scores on the Nursing Child Assessment Teaching Scale (NCATS). A
multivariable approach was used to identify maternal and child characteristics
associated with NCATS scores and to develop prediction models for NCATS total and
subscale scores of mothers and children. Child expressive and receptive
communication and maternal IQ, marital status, age, and insurance predicted NCATS
Mother total score, accounting for 28% of the score variance. Child expressive
communication and birth weight predicted the NCATS Child total score, accounting
for 4% of variance. Child's expressive communication and mother's IQ and marital
status predicted NCATS mother-child total scores. While these findings were
similar to reports of NCATS scores in at-risk populations, no previous teams
examined all of the mother and child characteristics included in this analysis.
These findings support the utility of the NCATS for assessing mother-child
interaction and predicting child outcomes in community-based, non-clinical
populations. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419487
TI - The Effect of Medicaid Physician Fee Increases on Health Care Access,
Utilization, and Expenditures.
AB - OBJECTIVE: To evaluate the effect of Medicaid fee changes on health care access,
utilization, and spending for Medicaid beneficiaries. DATA SOURCE: We use the
2008 and 2012 waves of the Medical Expenditure Panel Survey linked to state-level
Medicaid-to-Medicare primary care reimbursement ratios obtained through surveys
conducted by the Urban Institute. We also incorporate data from the Current
Population Survey and the Area Resource Files. STUDY DESIGN: Using a control
group made up of the low-income privately insured, we conduct a difference-in
differences analysis to assess the relationship between Medicaid fee changes and
access to care, utilization of health care services, and out-of-pocket medical
expenditures for Medicaid enrollees. PRINCIPAL FINDINGS: We find that an increase
in the Medicaid-to-Medicare payment ratio for primary care services results in an
increase in outpatient physician visits, emergency department utilization, and
prescription fills, but only minor improvements in access to care. In addition,
we report an increase in total annual out-of-pocket expenditures and spending on
prescription medications. CONCLUSIONS: Compared to the low-income privately
insured, increased primary care reimbursement for Medicaid beneficiaries leads to
higher utilization and out-of-pocket spending for Medicaid enrollees.
PMID- 28419486
TI - Population Pharmacokinetic Analysis of Bortezomib in Pediatric Leukemia Patients:
Model-Based Support for Body Surface Area-Based Dosing Over the 2- to 16-Year Age
Range.
AB - This population analysis described the pharmacokinetics of bortezomib after twice
weekly, repeat-dose, intravenous administration in pediatric patients
participating in 2 clinical trials: the phase 2 AALL07P1 (NCT00873093) trial in
relapsed acute lymphoblastic leukemia and the phase 3 AAML1031 (NCT01371981)
trial in de novo acute myelogenous leukemia. The sources of variability in the
pharmacokinetic parameters were characterized and quantified to support dosing
recommendations. Patients received intravenous bortezomib 1.3 mg/m2 twice-weekly,
on days 1, 4, and 8 during specific blocks or cycles of both trials and on day 11
of block 1 of study AALL07P1, in combination with multiagent chemotherapy. Blood
samples were obtained and the plasma was harvested on day 8 over 0-72 hours
postdose to measure bortezomib concentrations by liquid chromatography-tandem
mass spectrometry. Concentration-time data were analyzed by nonlinear mixed
effects modeling. Covariates were examined using forward addition (P <
.01)/backward elimination (P < .001). Data were included from 104 patients
(49%/51% acute lymphoblastic leukemia/acute myelogenous leukemia; 60%/40% aged 2
11 years/12-16 years). Bortezomib pharmacokinetics were described by a 3
compartment model with linear elimination. Body surface area adequately accounted
for variability in clearance (exponent 0.97), supporting body surface area-based
dosing. Stratified visual predictive check simulations verified that neither age
group nor patient population represented sources of meaningful pharmacokinetic
heterogeneity not accounted for by the final population pharmacokinetic model.
Following administration of 1.3 mg/m2 intravenous bortezomib doses, body surface
area-normalized clearance in pediatric patients was similar to that observed in
adult patients, thereby indicating that this dose achieves similar systemic
exposures in pediatric patients.
PMID- 28419488
TI - Interferon lambda3 gene (IL28B) is associated with spontaneous or treatment
induced viral clearance in hepatitis C virus-infected multitransfused patients
with thalassemia.
AB - BACKGROUND: Hepatitis C virus (HCV) is the major posttransfusion infection in
multitransfused individuals in India with thalassemia major. To our knowledge,
this study is the first conducted to correlate and comprehend the effects of the
host interleukin (IL)28B gene polymorphism at loci rs12979860 and rs8099917 in
spontaneous or interferon (IFN)-induced treatment response in the HCV
seroreactive individuals with thalassemia major. STUDY DESIGN AND METHODS: A
total of 557 HCV-seroreactive individuals with thalassemia were processed for HCV
viral genotyping and host IL28B single-nucleotide polymorphism analysis at loci
rs12979860 and rs8099917. RESULTS: Of 557 individuals, 70.92% were found to be
HCV RNA positive with Genotype 3 (95.18%) as predominant strain. A favorable CC
allele at locus rs2979860 and TT allele at rs8099917 were 75.31 and 77.16%,
respectively, which was strongly associated with spontaneous clearance of
infection (p < 0.05). Of 85 IFN-treated cases, 56 achieved sustained virologic
response (SVR) whereas 27 were relapsed cases. Among these patients who achieved
SVR, a favorable CC/TT allele at rs12979860/rs8099917 was found to be predominant
with 76.79 and 66.07%, respectively, whereas in the case of relapsed patients,
unfavorable CT (55.56%) and TG (59.26%) alleles were found to be predominant.
Additionally, low serum ferritin level was significantly associated with SVR.
CONCLUSION: CC at rs12979860 and TT at rs8099917 was strongly associated with
spontaneous clearance and SVR in the population with thalassemia. Low age group
and low serum ferritin level are important cofactors. This allelic pattern will
aid clinicians in making an informed decision about prognosis and therapeutic
management.
PMID- 28419490
TI - European cowpea landraces for a more sustainable agriculture system and novel
foods.
AB - BACKGROUND: Genetic diversity is fundamental to breeding programs and
consequently has an important role in obtaining new varieties. To properly use
the genetic diversity present in germplasm collections, a good knowledge of the
agro-morphological traits of each accession is needed. The aim of this study was
to explore the production capacity of 24 cowpea landraces from southern Europe,
through phenotypic characterization and evaluation in three different locations
in Greece and Portugal. RESULTS: Most qualitative parameters tested showed a high
stability among the three locations. A wide difference was observed among the
three locations with respect to number of days to flowering, ranging from 55 to
99 days. Quantitative traits showed a higher genotype * environment than genetic
variance component. In general, an inverse relationship between sigma2ge /sigma2g
ratio (where sigma2ge is genotype * genotype interaction and sigma2g is genotype
impact) and heritability value was observed. Principal component analysis was
able to group accessions based on their origin. The first two principal
components explained 97.52% of variation, being the number of seeds per plant,
plant height and seed protein content, the traits which contributed most to
variability. CONCLUSION: The results show that sufficient variation exists in
different traits within landraces in the studied cowpea germplasm to pursue a
breeding program. However, the quantitative traits showed a higher genotype *
environment component. (c) 2017 Society of Chemical Industry.
PMID- 28419491
TI - Intrinsic neural activity differences among psychotic illnesses.
AB - Individuals with psychosis have been reported to show either reduced or augmented
brain responses under seemingly similar conditions. It is likely that
inconsistent baseline-adjustment methods are partly responsible for this
discrepancy. Using steady-state stimuli during a pro/antisaccade task, this study
addressed the relationship between nonspecific and stimulus-related neural
activity, and how these activities are modulated as a function of cognitive
demands. In 98 psychosis probands (schizophrenia, schizoaffective disorder, and
bipolar disorder with psychosis), neural activity was assessed during baseline
and during a 5-s period in preparation for the pro/antisaccade task. To maximize
the ability to identify meaningful differences between psychosis subtypes,
analyses were conducted as a function of subgrouping probands by standard
clinical diagnoses and neurobiological features. These psychosis "biotypes" were
created using brain-based biomarkers, independent of symptomatology (Clementz et
al., ). Psychosis probands as a whole showed poor antisaccade performance and
diminished baseline oscillatory phase synchrony. Psychosis biotypes differed on
both behavioral and brain measures, in ways predicted from Clementz et al. ().
Two biotype groups showed similarly deficient behavior and baseline synchrony,
despite diametrically opposed neural activity amplitudes. Another biotype
subgroup was more similar to healthy individuals on behavioral and brain
measures, despite the presence of psychosis. This study provides evidence that
(a) consideration of baseline levels of activation and synchrony will be
essential for a comprehensive understanding of neural response differences in
psychosis, and (b) distinct psychosis subgroups exhibit reduced versus augmented
intrinsic neural activity, despite cognitive performance and clinical
similarities.
PMID- 28419492
TI - Expression and trafficking of MR1.
AB - MHC class I-related gene protein (MR1) is a non-polymorphic MHC class IB antigen
presenting molecule that is the restricting molecule for mucosal-associated
invariant T (MAIT) cells, a prominent population of innate-like antibacterial T
cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation,
with the MR1 ligand derived from vitamin B compounds or their metabolic
precursors. Many bacteria and some fungi produce the activating ligand for MR1.
In evolution, MR1 is highly conserved in most, but not all, mammals. In humans
and rodents it is expressed in a broad range of cell types, both haematopoietic
and non-haematopoietic, although cell surface expression has been difficult to
detect. Although MR1 trafficking shares features with both the MHC class I and
MHC class II pathways, it is distinct. Several strands of evidence suggest that
the intracellular location where MR1 is loaded differs for soluble ligand and for
ligand derived from intact bacteria. The regulation of MR1 surface expression may
also vary between different cell types. This paper will review what is currently
known about the expression and trafficking of MR1 and propose a model for the
loading and trafficking of MR1.
PMID- 28419493
TI - Distribution of the tick Dermacentor reticulatus in the United Kingdom.
AB - The recent implication of Dermacentor reticulatus (Ixodida: Ixodidae) in the
transmission of canine babesiosis in the U.K. has highlighted the lack of
accurate published data on its distribution in this country. This paper aims to
collate and appraise historical data for D. reticulatus, to supplement such data
with more recent surveillance data and to report on field sampling conducted
during 2009-2016. These updated data facilitate better understanding of the
current distribution of this tick in the U.K., which will better inform disease
risk assessments. There appear to be four known regions of the U.K. in which D.
reticulatus currently occurs, including western Wales, North and South Devon, and
Essex. The majority of foci are located in coastal sand dunes and maritime
grasslands, including grazing marsh. However, more recently the tick has been
detected in urban greenspace in Essex. The emergence of this tick as a vector of
babesiosis in the U.K. and its recent apparent spread in Essex into urban
greenspace highlight the need for continued surveillance and for further research
into its status as a vector of human and veterinary pathogens.
PMID- 28419494
TI - Increased levels of soluble CD163 in periodontitis patients.
AB - AIM: Soluble CD163 (sCD163) has been implicated as a new biomarker in
inflammatory conditions. The aim of this cross-sectional study was to assess
CD163 levels systemically and locally in patients with chronic periodontitis.
METHODS: sCD163 levels were measured by ELISA in serum samples from 70
periodontitis and 70 periodontally healthy subjects, and in saliva samples in a
subset of the population. Two gingival biopsies were harvested per subject from
20 periodontitis patients: one from a periodontally affected site, the other from
a healthy site, and the relative expression of CD163 mRNA was assessed by real
time PCR. RESULTS: Serum sCD163 was significantly higher in periodontitis
patients compared to periodontally healthy subjects (720.0 +/- 330.6 ng/ml versus
510.7 +/- 219.6 ng/ml, respectively; p < .001). Similarly, sCD163 levels in
saliva were significantly increased in periodontitis compared to healthy subjects
(3.01 +/- 5.07 ng/ml versus 1.98 +/- 4.95 ng/ml, respectively; p = .009). Serum
and saliva sCD163 levels showed a positive correlation (Kendall's tau .27, p =
.018). Importantly, CD163 gene expression was significantly higher in affected
sites compared to unaffected sites in periodontitis patients, with a mean fold
upregulation of 9.9 (STD: 15.3, p = .010). CONCLUSION: Our findings suggest that
CD163 may be involved in the pathogenesis of periodontitis and its link with
systemic conditions.
PMID- 28419495
TI - Giant proliferating trichilemmal cyst arising from a nevus sebaceus growing for
30 years.
AB - Nevus sebaceus of Jadassohn, a congenital cutaneous hamartoma, has the potential
to develop into various epidermal adnexal-origin neoplasms. While the most common
neoplasms are trichoblastoma or syringocystadenoma, proliferating trichilemmal
cysts are exceptionally rare. We report a case of a 63-year-old Cuban male with a
giant proliferating trichilemmal cyst arising from a nevus sebaceus on the right
shoulder which had been growing for 30 years. Proliferating trichilemmal cysts
arising from nevus sebaceus cases are difficult to diagnose clinically and
histologically as they are very rare and have not been defined by exact
diagnostic criteria. Our case creates awareness of this particular tumor in nevus
sebaceus and shares clinical and histological diagnostic information that can be
used to make a proper diagnosis.
PMID- 28419496
TI - Emotionally Focused Couple Therapy for Parents Raising a Child with an Autism
Spectrum Disorder: A Pilot Study.
AB - Many couples raising children diagnosed with an Autism Spectrum Disorder (ASD)
are often resilient in confronting unique parental demands, while others
experience greater risk for relational distress. Research has shown that
Emotionally Focused Couple Therapy (EFT) is efficacious with couples raising
chronically ill children and relevant to the relational demands of parents of
children diagnosed with an ASD. This pilot study tested the effectiveness of EFT
with seven couples presenting with moderate to severe distress, who were also
parents of a child diagnosed with an ASD. Results demonstrated significant
decreases in marital distress at posttreatment and 6-month follow-up. The study
also identified several unique themes associated with couple distress and the
parenting experiences of this population.
PMID- 28419498
TI - Perceptions and Experiences of Marriage Preparation Among U.S. Muslims: Multiple
Voices from the Community.
AB - Although Muslims in the United States are a growing population, there is limited
research on their relational patterns and how they prepare for marriage. We
conducted in-depth interviews with 32 members of the Muslim community in
Southeast Michigan including married individuals, divorced individuals,
therapists, and imams (Muslim religious leaders) to explore their perceptions and
experiences of marriage preparation. Our analysis revealed that marriage
preparation varies but is less likely to involve a requirement of premarital
counseling, with imams being the primary providers, not therapists. Barriers to
participation include stigma, lack of awareness, logistical and financial
challenges, and parental influence. Partnerships between imams and therapists,
and family and community efforts are necessary to address barriers and increase
participation in premarital education programs.
PMID- 28419497
TI - Predictors of long-term outcomes in patients undergoing periodontal maintenance.
AB - AIM: This retrospective study aimed to characterize the baseline status of
patients following periodontal maintenance, analysing the association between the
long-term outcome of these patients, smoking, bruxism, and the main clinical and
radiographic variables. MATERIAL AND METHODS: A sample of 174 patients with
moderate to severe periodontitis was refined into homogeneous subsamples
according to smoking and bruxism and the rate of tooth loss due to periodontal
disease (TLPD): 0, 1-2, and >2 teeth. The association and the distribution (chi2
test) of the variables within the subsamples were analysed. RESULTS: Smoking and
bruxism were significantly associated with higher TLPD rates. Vertical and
circumferential bone defects (p < .0001), and abfractions (p < .0001) were
associated with bruxism and particularly with bruxism and TLPD >2. Furcation
defects (p = .0002), fewer radio-opaque subgingival calculus (chi2 p < .0001), a
lower mean Gingival index (chi2 p = .027), and increased mean recessions >1.5 mm
(chi2 p = .0026) were associated with smoking and higher TLPD rates. The mean
baseline mobility, abfractions, and recessions characterized two basic types of
TLPD. CONCLUSIONS: Smoking, bruxism, and routine clinical and radiological
parameters can be used to characterize the baseline status of patients with worse
outcomes.
PMID- 28419499
TI - Periodontitis changes renal structures by oxidative stress and lipid
peroxidation.
AB - OBJECTIVE: The aim of this study was to investigate whether experimental
periodontitis cause changes to the renal tissues and imbalance in oxidative
stress in kidneys. METHODS: Twenty-two female Wistar rats were separated into two
groups: control and periodontitis. We assessed the following parameters: gingival
bleeding index (GBI), tooth mobility, gum malondialdehyde (MDA), myeloperoxidase
(MPO) activity, probing pocket depth (PPD), alveolar bone loss (ABL) for
periodontal tissues; histomorphometric measures associated with renal corpuscle
and histopathological aspects (evaluation of brush border) for kidneys; as also
blood and urine biomarkers. Finally, we evaluated renal oxidative stress through
glutathione (GSH) and MDA respectively. RESULTS: With regard to renal
histomorphometry, significant differences were observed in all parameters
assessed. In relation periodic acid Schiff (PAS) staining, disruption was
observed of brush border in the periodontitis group in the renal tubules in
comparison with the control group. The periodontitis group presented
significantly higher MDA and lower GSH concentrations in the kidneys compared
with animals without periodontitis. CONCLUSION: The induced periodontitis caused
histomorphometric changes in renal tissues as well as disruption of the brush
border in renal tubules, alterations associated with increase in oxidative stress
in kidneys. However, these alterations were not sufficient to cause differences
in the renal function markers.
PMID- 28419500
TI - Antepartum management and obstetric outcomes among pregnancies with Down syndrome
from diagnosis to delivery.
AB - OBJECTIVE: Little is known about the obstetric care of an ongoing pregnancy with
trisomy 21. We sought to ascertain an obstetric profile for pregnancies with Down
syndrome to help guide prenatal management. METHOD: Pregnancies managed for
delivery with trisomy 21 between 2003 and 2014 were analyzed. We reviewed
demographic data, diagnostic testing, prenatal surveillance, obstetric outcomes,
and placental pathology. T-test, chi-squared test, and Fisher correction were
used as indicated. RESULTS: Sixty-eight pregnancies were identified, and four
women (5.9%) experienced a loss during the pregnancy. Among the remaining 64
pregnancies, the average gestational age at delivery was 36.9 weeks, growth
restriction was present in 12 (17.5%), and major anomalies were present in 51
(75.0%). Delivery was undertaken for non-reassuring fetal surveillance in 35.9%
of the pregnancies; 93% of which represented a change from prior reassuring
surveillance and 52.6% of which demonstrated histopathologic evidence of
placental insufficiency. None among increased maternal age, the presence of an
anomaly, or growth restriction were significantly more common in the group with
non-reassuring surveillance. CONCLUSION: There are high rates of fetal growth
restriction, delivery for non-reassuring fetal status, and evidence of placental
insufficiency among affected pregnancies, suggesting a role for antepartum
surveillance. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419501
TI - Stakeholders' views of the introduction of assistive technology in the classroom:
How family-centred is Australian practice for students with cerebral palsy?
AB - BACKGROUND: With family-centred care widely recognized as a cornerstone for
effective assistive technology service provision, the current study was
undertaken to investigate to what extent such approaches were used by schools
when assistive technology assessments and implementation occurred in the
classroom. METHOD: In this cross-sectional study, we compare survey results from
parents (n = 76), school staff (n = 33) and allied health professionals (n = 65)
with experience in the use of high-tech assistive technology. Demographic
characteristics and the stakeholders' perceived helpfulness and frequency
attending assessment and set-up sessions were captured. To evaluate how family
centred the assistive technology services were perceived to be, the parents
filled out the Measure of Processes of Care for Caregivers, and the professionals
completed the Measure of Processes of Care for Service Providers. Descriptive
statistics and one-way analysis of variance were used to conduct the data
analysis. RESULTS: Findings show that parents are more involved during the
assessment stage than during the implementation and that classroom teachers are
often not involved in the initial stage. Speech pathologists in particular are
seen to be to a great extent helpful when implementing assistive technology in
the classroom. This study found that family-centred service is not yet fully
achieved in schools despite being endorsed in early intervention and disability
services for over 20 years. No statistically significant differences were found
with respect to school staff and allied health professionals' roles, their years
of experience working with students with cerebral palsy and the scales in the
Measure of Processes of Care for Service Providers. CONCLUSION: To enhance the
way technology is matched to the student and successfully implemented, classroom
teachers need to be fully involved in the whole assistive technology process. The
findings also point to the significance of parents' involvement, with the support
of allied health professionals, in the process of selecting and implementing
assistive technology in the classroom.
PMID- 28419502
TI - Nuchal translucency measurement, free beta-hCG and PAPP-A concentrations in
IVF/ICSI pregnancies: systematic review and meta-analysis.
AB - So far, data on the effect of assisted reproductive technologies (ART) on the
components of first trimester combined screening for Down syndrome are still
controversial. A systematic search of the literature was performed in order to
identify the effect of ART, particularly in vitro fertilization (IVF) and
intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal
translucency, free beta-human chorionic gonadotrophin and pregnancy-associated
plasma protein-A measurements. Moreover, a meta-analysis and a descriptive
graphical representation of the ratios between ART and spontaneous pregnancies
(controls) values of median of the multiple of median (m0 MoM) were performed.
Free beta-human chorionic gonadotrophin test showed slightly higher values in the
ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group
(RR = 1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for
IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI
0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal
translucency measurement did not show any statistical differences between study
groups (IVF and ICSI) and controls (RR = 1.00, 95%CI: 0.94-1.08 and RR = 1.01,
95%CI: 0.97-1.05, respectively). These results may be due to alterations in the
placentation of ART pregnancies. Differentiating further subgroups of ART
pregnancies may explain the differences in biomarker concentrations, in prenatal
behavior and in obstetric outcomes between ART and spontaneous pregnancies. (c)
2017 John Wiley & Sons, Ltd.
PMID- 28419503
TI - Comparison of the quantitative dry culture methods with both conventional media
and most probable number method for the enumeration of coliforms and Escherichia
coli/coliforms in food.
AB - : Sanita-kunTM CC (coliform count) and EC (Escherichia coli/coliform count),
sheet quantitative culture systems which can avoid chromogenic interference by
lactase in food, were evaluated in comparison with conventional methods for these
bacteria. Based on the results of inclusivity and exclusivity studies using 77
micro-organisms, sensitivity and specificity of both Sanita-kunTM met the
criteria for ISO 16140. Both media were compared with deoxycholate agar, violet
red bile agar, Merck ChromocultTM coliform agar (CCA), 3M PetrifilmTM CC and EC
(PEC) and 3-tube MPN, as reference methods, in 100 naturally contaminated food
samples. The correlation coefficients of both Sanita-kunTM for coliform detection
were more than 0.95 for all comparisons. For E. coli detection, Sanita-kunTM EC
was compared with CCA, PEC and MPN in 100 artificially contaminated food samples.
The correlation coefficients for E. coli detection of Sanita-kunTM EC were more
than 0.95 for all comparisons. There were no significant differences in all
comparisons when conducting a one-way analysis of variance (anova). Both Sanita
kunTM significantly inhibited colour interference by lactase when inhibition of
enzymatic staining was assessed using 40 natural cheese samples spiked with
coliform. Our results demonstrated Sanita-kunTM CC and EC are suitable
alternatives for the enumeration of coliforms and E. coli/coliforms,
respectively, in a variety of foods, and specifically in fermented foods.
SIGNIFICANCE AND IMPACT OF THE STUDY: Current chromogenic media for coliforms and
Escherichia coli/coliforms have enzymatic coloration due to breaking down of
chromogenic substrates by food lactase. The novel sheet culture media which have
film layer to avoid coloration by food lactase have been developed for
enumeration of coliforms and E. coli/coliforms respectively. In this study, we
demonstrated these media had comparable performance with reference methods and
less interference by food lactase. These media have a possibility not only to be
useful alternatives but also to contribute for accurate enumeration of these
bacteria in a variety of foods, and specifically in fermented foods.
PMID- 28419504
TI - Sensory and rheological characteristics of thickened liquids differing
concentrations of a xanthan gum-based thickener.
AB - : The objectives of this study were to develop and compare sensory
characteristics of beverages and soups thickened with different concentrations of
a xanthan gum-based thickener, and to examine, using rheological measurement,
whether the viscosity of the thickened liquids conformed to the recommendations
of the National Dysphagia Diet (NDD) Task Force. Beverages tested included water,
apple juice, orange juice, soymilk, and Yakult. The thickening agent was added to
samples at concentrations of 1, 2, or 3%. Addition of the thickening agent had a
significant effect on the appearance, texture, and starchy flavor, which were
evaluated by descriptive sensory evaluation. The reference standards of viscosity
used in sensory descriptive analysis could be useful to practitioners who have to
make dysphagia diets and need to learn to make them properly. In rheological
measurement, viscosity of thickened liquids in stationary state would be
perceived as higher compared to that while swallowing, because of the shear
thinning property. This could lead to noncompliance of the medical advice or
malnutrition. It is necessary to determine optimal proportion of xanthan gum
based thickener or uncover alternatives, which have shear thinning properties
lower than those of xanthan gum, for the acceptance of dysphagia patients. There
was no pudding-like viscosity as classified by NDD, when prepared following
instructions. Future studies should include higher concentrations of thickener to
find out the concentration of the thickener resulting in pudding-like viscosity
as recommended by NDD. PRACTICAL APPLICATIONS: When a manufacturer modifies or
develops a xanthan gum-based thickener, findings from this study can be utilized
to understand sensory and rheological characteristics of thickened liquid. For
practitioners who have to make dysphagia diets, the reference standards of
viscosity used in sensory descriptive analysis could be helpful for deciding the
viscosity level of thickened liquids based only on visual evaluation. This study
suggests manufacturers should provide clear direction for viscosity range and
thickener concentration. Medical doctors should pay close attention to the risk
of aspiration when prescribing pudding-like viscosity. Dietitians should
understand the variability in achieving different levels of viscosity and should
educate preparers who are responsible for making dysphagia meals.
PMID- 28419505
TI - Assisted Dying & Disability.
AB - This article explores at least two dominant critiques of assisted dying from a
disability rights perspective. In spite of these critiques, I conclude that
assisted dying ought to be permissible. I arrive at the conclusion that if we
respect and value people with disabilities, we ought to permit assisted dying. I
do so in the following manner. First, I examine recent changes in legislation
that have occurred since the Royal Society of Canada Expert Panel on End-of-Life
Decision-Making report, published in this journal. I suggest that these changes
are likely to only strengthen opposition to assisted dying from disability rights
activists and people with disabilities. Second, I focus on respect for people
with disabilities and in particular, respect for their autonomy and decision
making abilities. Third, I explore the opposition to assisted dying that focuses
on risk and the vulnerability of people with disabilities. Here I suggest that
this risk ought not to be of special concern. Ultimately, I conclude that
upholding respect for the disabled requires the legalization of assisted dying,
rather than the denial of access in a misguided effort to protect people with
disabilities.
PMID- 28419506
TI - Neuronal loss, demyelination and volume change in the multiple sclerosis
neocortex.
AB - AIMS: Indices of brain volume [grey matter, white matter (WM), lesions] are being
used as outcomes in clinical trials of patients with multiple sclerosis (MS). We
investigated the relationship between cortical volume, the number of neocortical
neurons estimated using stereology and demyelination. METHODS: Nine MS and seven
control hemispheres were dissected into coronal slices. On sections stained for
Giemsa, the cortex was outlined and optical disectors applied using systematic
uniform random sampling. Neurons were counted using an oil immersion objective (*
60) following stereological principles. Grey and WM demyelination was outlined on
myelin basic protein immunostained sections, and expressed as percentages of
cortex and WM respectively. RESULTS: In MS, the mean number of neurons was 14.9
+/- 1.9 billion vs. 24.4 +/- 2.4 billion in controls (P < 0.011), a 39%
difference. The density of neurons was smaller by 28% (P < 0.001) and cortical
volume by 26% (P = 0.1). Strong association was detected between number of
neurons and cortical volume (P < 0.0001). Demyelination affected 40 +/- 13% of
the MS neocortex and 9 +/- 12% of the WM, however, neither correlated with
neuronal loss. Only weak association was detected between number of neurons and
WM volume. CONCLUSION: Neocortical neuronal loss in MS is massive and strongly
predicted by cortical volume. Cortical volume decline detected in vivo may be
similarly indicative of neuronal loss. Lack of association between neuronal
density and demyelination suggests these features are partially independent, at
least in chronic MS.
PMID- 28419507
TI - A rapid solvent accessible surface area estimator for coarse grained molecular
simulations.
AB - The rapid and accurate calculation of solvent accessible surface area (SASA) is
extremely useful in the energetic analysis of biomolecules. For example, SASA
models can be used to estimate the transfer free energy associated with
biophysical processes, and when combined with coarse-grained simulations, can be
particularly useful for accounting for solvation effects within the framework of
implicit solvent models. In such cases, a fast and accurate, residue-wise SASA
predictor is highly desirable. Here, we develop a predictive model that estimates
SASAs based on Calpha-only protein structures. Through an extensive comparison
between this method and a comparable method, POPS-R, we demonstrate that our new
method, Protein-C alpha Solvent Accessibilities or PCASA, shows better
performance, especially for unfolded conformations of proteins. We anticipate
that this model will be quite useful in the efficient inclusion of SASA-based
solvent free energy estimations in coarse-grained protein folding simulations.
PCASA is made freely available to the academic community at
https://github.com/atfrank/PCASA. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419508
TI - Experience of carrier couples identified through a population-based carrier
screening pilot program for four founder autosomal recessive diseases in Saguenay
Lac-Saint-Jean.
AB - : A pilot population-based carrier screening program started in 2010 in the
Saguenay-Lac-Saint-Jean region of Quebec, Canada, for four recessive diseases
with local founder effects (tyrosinemia type I, autosomal recessive spastic
ataxia of Charlevoix-Saguenay, congenital lactic acidosis, and Andermann
syndrome). OBJECTIVES: The objective of this study was to describe the experience
of carrier couples identified through this program. METHODS: Semi-structured
interviews were performed with carrier couples. Thematic analysis of interview
transcripts was performed to identify emerging themes. RESULTS: Interviews were
performed with 15 carrier couples (56% response rate). Carrier couples had little
knowledge about the target diseases before being identified as carriers, despite
pre-test education sessions. The main motivation for screening was a
recommendation by a peer who had been screened, even for those with a positive
family history of one of the target conditions. Couples perceived themselves at
low risk of being a carrier couple, whatever their family history. Being found to
be a carrier couple was initially a shock, illustrating how ill prepared they
were for such a result, but carrier couples appreciated knowing their status.
CONCLUSION: Our results emphasize the informational needs of couples to make
informed decisions and the importance of post-test counseling for those with
positive results. Our findings can inform counseling procedures in expanded
carrier screening. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419509
TI - Automatic diagnosis of vulvovaginal candidiasis from Pap smear images.
AB - Vulvovaginal candidiasis (VVC) is the most common genital infections that are
seen every day in clinics. This infection is due to excessive growth of Candida
that are normally present in the vagina in small numbers. Diagnosis of VVC is
routinely done by direct microscopy of Pap smear samples and searching for the
Candida in the Pap smear glass slides. This manual method is subjective, time
consuming, labour-intensive and tedious. This study presents a computer-aided
diagnostic (CAD) method to improve human diagnosis of VVC. The proposed CAD
method reduces the diagnostic time and also can be worked as a second objective
opinion for pathologists. Our main objective is detection and extraction of
mycelium and conidium of Candida fungus from microscopic images of Pap smear
samples. In this regard, the proposed method is composed of three main phases,
namely preprocessing, segmentation, feature extraction and classification. At the
first phase, bottom-hat filtering is used for elimination of the cervical cells
and separating the background. Then decorrelation stretching and colour K-means
clustering are used for Candida segmentation. Finally the extracted features used
by a decision tree classifier to detect Candida from other parts of smear. The
proposed method was evaluated on 200 Pap smear images and showed specificity of
99.83% and 99.62% and sensitivity of 92.18% and 94.53% for detection of mycelium
and conidium, respectively.
PMID- 28419511
TI - Analysis of the variability of food texture properties: Application to the
fracturability of dry pet food.
AB - : An original stochastic finite element method (SFEM) is proposed for the texture
analysis of food products for which samples cannot be standardized. SFEM is able
to distinguish shape and texture variability. As an illustration, the methodology
is applied to dry cat food using compression testing. First, a deterministic
damage elastic model depending on six mechanical and three size parameters is
shown to fit adequately experimental data. Then, Morris screening method is
applied to FEM data: this highlights that the variability of compression tests is
significantly affected by two mechanical and two size parameters. Finally, the
nonlinear variability of each control variable is estimated from Sobol indices
derived from a time-efficient stochastic collocation method. These highlight that
the contribution of size parameters to test variability is about 20%. Therefore,
a robust estimation of the probability density function of texture properties can
be obtained for improved quality control, which outperforms current methods.
PRACTICAL APPLICATIONS: Food texture is affected by their material property and
geometrical structure. Material properties are difficult to estimate when the
size and shape of the samples cannot be standardized, for example, for snack or
pet food. In addition, the intrinsic variability of material properties due to
the recipe and the process cannot be neglected. But this cannot be easily
distinguished from the variability of geometrical parameters using conventional
methods. An innovative approach using stochastic finite element method is
developed and is able to exhibit the major parameters influencing the variability
of the response to mechanical testing. This methodology may be helpful to improve
acceptance sampling control procedures, for example, by combining texture and
size measurements when necessary, or by better determining the most robust
response variables for decision-making.
PMID- 28419510
TI - Increase of aquaporin 9 expression in astrocytes participates in astrogliosis.
AB - Here we assess the potential functional role of increased aquaporin 9 (APQ9) in
astrocytes. Increased AQP9 expression was achieved in primary astrocyte cultures
by transfection of a plasmid-containing green fluorescent protein fused to either
wild-type or mutated human AQP9. Increased AQP9 expression and phosphorylation at
Ser222 were associated with a significant change in astrocyte morphology, mainly
with a higher number of processes. Similar phenotypic changes are observed in
astrogliosis processes after injury. In parallel, we observed that in vivo,
thrombin preconditioning before ischemic stroke induced an early increase in AQP9
expression in the male mouse brain. This increased AQP9 expression was also
associated with astrocyte morphological changes, especially in the white matter
tract. Astrocyte reactivity is debated as being either beneficial or deleterious.
As thrombin preconditioning leads to a decrease in lesion size after stroke, our
data suggest that the early increase in AQP9 concomitant with astrocyte
reactivity leads to a beneficial effect. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419512
TI - Predicting receptor functionality of signaling lymphocyte activation molecule for
measles virus hemagglutinin by docking simulation.
AB - Predicting susceptibility of various species to a virus assists assessment of
risk of interspecies transmission. Evaluation of receptor functionality may be
useful in screening for susceptibility. In this study, docking simulation was
conducted for measles virus hemagglutinin (MV-H) and immunoglobulin-like variable
domain of signaling lymphocyte activation molecule (SLAM-V). It was observed that
the docking scores for MV-H and SLAM-V correlated with the activity of SLAM as an
MV receptor. These results suggest that the receptor functionality may be
predicted from the docking scores of virion surface proteins and cellular
receptor molecules.
PMID- 28419513
TI - Genetic Recombination Between Stromal and Cancer Cells Results in Highly
Malignant Cells Identified by Color-Coded Imaging in a Mouse Lymphoma Model.
AB - The tumor microenvironment (TME) promotes tumor growth and metastasis. We
previously established the color-coded EL4 lymphoma TME model with red
fluorescent protein (RFP) expressing EL4 implanted in transgenic C57BL/6 green
fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma TME suggested
an important role of stromal cells in lymphoma progression and metastasis. In the
present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal
cells to identify yellow-fluorescent genetically recombinant cells appearing only
during metastasis. The EL4-RFP lymphoma cells were injected subcutaneously in
C57BL/6-GFP transgenic mice and formed subcutaneous tumors 14 days after cell
transplantation. The subcutaneous tumors were harvested and transplanted to the
abdominal cavity of nude mice. Metastases to the liver, perigastric lymph node,
ascites, bone marrow, and primary tumor were imaged. In addition to EL4-RFP cells
and GFP-host cells, genetically recombinant yellow-fluorescent cells, were
observed only in the ascites and bone marrow. These results indicate genetic
exchange between the stromal and cancer cells. Possible mechanisms of genetic
exchange are discussed as well as its ramifications for metastasis. J. Cell.
Biochem. 118: 4216-4221, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419514
TI - Activation of TLR7 Inhibition of Mycobacterium Tuberculosis Survival by Autophagy
in RAW 264.7 Macrophages.
AB - The aim of the study was to evaluate the effect of regulation of TLR7 on
Mycobacterium tuberculosis (Mtb) survival in macrophages. TLR7 expression in
macrophages infected by Mtb was detected by RT-PCR and Western blotting.
Regulation of TLR7 was achieved by single strand RNA (ssRNA) or siRNA. The
effects of TLR7 on Mtb survival and cell viability were detected by acid fast
staining and cell counting kit-8, respectively. Cell ultrastructure was observed
via transmission electron microscopy (TEM), and autophagy related protein LC3 was
analyzed by Western blotting. TLR7 in Mtb infected macrophages was up-regulated
and up-regulation of TLR7 could eliminate intracellular Mtb. Up-regulation of
TLR7 could increase viability of Mtb infected cells, while down-regulation of
TLR7 induced decrease of cell viability compared with the controls. Autophagosome
was significantly increased in the Mtb infected macrophages after up-regulation
of TLR7 and LC3-II protein showed obvious increase compared with the controls.
Autophagosome could not be detected in macrophages after down-regulation of TLR7,
rough endoplasmic reticulum was dilated, and nuclear week gap was widened.
Moreover, LC3-II protein was reduced in Mtb infected macrophages based upon the
down-regulation of TLR7. Up-regulation of TLR7 could eliminate intracellular Mtb
through autophagy. J. Cell. Biochem. 118: 4222-4229, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28419515
TI - Incivility in the Online Classroom: A Guide for Policy Development.
AB - The growth of online education has created a learning environment that permits
nontraditional students the opportunity for degree completion without the burden
of relocation. Given the shortage of nurses at all educational levels, many
institutions of higher learning have created online programs to meet the needs of
both the student and the profession as a whole. Although convenient for the
student and beneficial for the nursing profession, the online learning
environment can present numerous challenges. Among these challenges are acts of
student incivility-creating a difficult work environment for faculty and, at
times, negatively affecting other students. Therefore, the purpose of this
article is to review problems associated with student incivility and share the
experience in creating as well as implementing a professionalism policy that
addresses student incivility. Recommendations for policy creation are summarized.
PMID- 28419516
TI - Systemic and local anti-nociceptive effects of simvastatin in the rat formalin
assay: Role of peroxisome proliferator-activated receptor gamma and nitric oxide.
AB - This study aimed to determine the potential systemic and local anti-nociceptive
effects of simvastatin (SIM) and the possible role of peroxisome proliferator
activated receptor gamma (PPARgamma) and nitric oxide (NO) pathways using a
formalin assay in rats. After allocation, rats were intraplantarly (i.pl.)
treated with formalin solution (2.5%) and the flinching behaviors were recorded
for 5 min (phase 1) and 15-60 min (phase 2). SIM was given intraperitoneally
(i.p.) and i.pl. 30 and 20 min before test, respectively. Intraperitoneal
administration of SIM attenuated the flinching number during both phases of the
test. This effect of i.p. SIM was significantly reduced by L -NAME (NO synthase
blocker, i.p.), but was augmented by L -arginine (NO precursor, i.p.) during both
phases of the formalin assay. Moreover, the antinociception caused by i.p. SIM
was blocked by GW-9662 (PPARgamma antagonist) at dose 2 mg/kg (i.p.). In another
experiment, concurrent ip administration of non-effective dose of simvastatin (5
mg/kg) with pioglitazone (PPARgamma agonist; 10, 20 mg/kg) produced
antinociception. However, pre-treatment with i.p. GW-9662 inhibited the enhanced
antinociceptive effect of pioglitazone on SIM during the phase 2 of formalin
assay. Results also showed that i.pl. SIM alone had no anti-nociceptive effects.
However, significant anti-nociception was observed when SIM (i.pl.) co
administered with non-effective dose of pioglitazone. Moreover, the enhanced
effect was antagonized by pre-treatment with i.pl. GW-9662. Our data suggest that
SIM produced antinociception through systemic but not local route of
administration in rats. Moreover, the antinociceptive effect of SIM is partly
mediated through PPARgamma receptors and NO pathway. (c) 2017 Wiley Periodicals,
Inc.
PMID- 28419517
TI - Comparative analysis between RQ-PCR and digital droplet PCR of BCL2/IGH gene
rearrangement in the peripheral blood and bone marrow of early stage follicular
lymphoma.
AB - BCL2/IGH rearrangements were analysed by polymerase chain reaction (PCR) at
diagnosis in paired peripheral blood (PB) and bone marrow (BM) samples from 67
patients with stage I/II follicular lymphoma (FL). Real time quantitative PCR (RQ
PCR) and digital droplet PCR (ddPCR) were performed in cases with a major
breakpoint region (MBR+) at diagnosis and after localized radiotherapy and
rituximab administration in order to investigate the applicability of ddPCR. The
overall ddPCR/RQ-PCR concordance was 81.9% (113/138 samples) and 97.5% in the
40/138 with quantifiable disease (RQ-PCR>=10-5 ). At baseline, ddPCR allowed the
recovery of a MBR+ marker in 8/18 (44.4%) samples that resulted MBR
negative/minor cluster region-negative/minor BCL2-negative by qualitative PCR.
Moreover, the tumour burden at diagnosis significantly predicted progression-free
survival (PSF) only when quantified by ddPCR. Paired PB and BM samples analysis
demonstrated a high concordance in the detection of BCL2/IGH+ cells by
qualitative and quantitative methods; in particular, 40/62 samples were positive
by ddPCR (25 PB+/BM+; 9 PB+/BM-; 6 PB-/BM+), with 34/40 (85%) identified by the
study of PB only. In conclusion, in localized FL, ddPCR is a promising tool for
monitoring minimal residual disease (MRD) that is at least comparable to RQ-PCR
and potentially more accurate. PB is a suitable source for serial BCL2/IGH MRD
assessments, regardless of the methodology utilized.
PMID- 28419518
TI - Public preferences on written informed consent for low-risk pragmatic clinical
trials in Spain.
AB - AIMS: Pragmatic randomized clinical trials (pRCTs) collect data that have the
potential to improve medical care significantly. However, these trials may be
undermined by the requirement to obtain written informed consent, which can
decrease accrual and increase selection bias. Recent data suggest that the
majority of the US public endorses written consent for low-risk pRCTs. The
present study was designed to assess whether this view is specific to the US.
METHODS: The study took the form of a cross-sectional, probability-based survey,
with a 2 * 2 factorial design, assessing support for written informed consent vs.
verbal consent or general notification for two low-risk pRCTs in hypertension,
one comparing two drugs with similar risk/benefit profiles and the other
comparing the same drug being taken in the morning or at night. The primary
outcome measures were respondents' personal preference and hypothetical
recommendation to a research ethics committee regarding the use of written
informed consent vs. the alternatives. RESULTS: A total of 2008 adults sampled
from a probability-based online panel responded to the web-based survey conducted
in May 2016 (response rate: 61%). Overall, 77% of respondents endorsed written
consent. In both scenarios, the alternative of general notification received
significantly more support (28.7-37.1%) than the alternative of verbal consent
(12.7-14.0%) (P = 0.001). Forty per cent of respondents preferred and/or
recommended general notification rather than written consent. CONCLUSIONS: The
results suggested that, rather than attempting to waive written consent, current
pRCTs should focus on developing ways to implement written consent that provide
sufficient information without undermining recruitment or increasing selection
bias. The finding that around 40% of respondents endorsed general notification
over written consent raises the possibility that, with educational efforts, the
majority of Spaniards might accept general notification for low-risk pRCTs.
PMID- 28419520
TI - Case with acute urticaria by red meat after Haemaphysalis longicornis bite.
PMID- 28419521
TI - Cytokinetic Abscission: Phosphoinositides and ESCRTs Direct the Final Cut.
AB - Cytokinetic abscission involves the fine and regulated recruitment of membrane
remodeling proteins that participate in the abscission of the intracellular
bridge that connects the two dividing cells. This essential process is mediated
by the concomitant activity of the endosomal sorting complex required for
transport (ESCRT) and the vesicular trafficking directed to the midbody.
Phosphoinositides (PtdIns), produced at plasma membrane, and endosomes, act as
molecular intermediates by recruiting effector proteins involved in multiple
cellular processes, such as intracellular signaling, endo- and exo-cytosis, and
membrane remodeling events. Emerging evidences suggest that PtdIns have an active
role in recruiting key elements that control the stability and the remodeling of
the cytoskeleton from the furrow ingression to the abscission, at the end of
cytokinesis. Accordingly, a possible concomitant and coordinated activity between
PtdIns production and ESCRT machinery assembly could also exist and recent
findings are pointing the attention on poorly understood ESCRT subunits
potentially able to associate with PtdIns rich membranes. Although further
studies are required to link PtdIns to ESCRT machinery during abscission, this
might represent a promising field of study. J. Cell. Biochem. 118: 3561-3568,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419519
TI - Deletion of a Distal RANKL Gene Enhancer Delays Progression of Atherosclerotic
Plaque Calcification in Hypercholesterolemic Mice.
AB - Receptor activator of NF-kappaB ligand (RANKL) is a TNF-like cytokine which
mediates diverse physiological functions including bone remodeling and immune
regulation. RANKL has been identified in atherosclerotic lesions; however, its
role in atherosclerotic plaque development remains elusive. An enhancer located
75 kb upstream of the murine Rankl gene's transcription start site designated D5
is important for its calciotropic hormone- and cytokine-mediated expression.
Here, we determined the impact of RANKL levels in atherosclerotic plaque
development in the D5 enhancer-null (D5-/- ) mice in an atherogenic Apoe-/-
background fed a high-fat diet (HFD). Rankl mRNA transcripts were increased in
aortic arches and thoracic aortae of Apoe-/- mice; however, this increase was
blunted in Apoe-/- ;D5-/- mice. Similarly, higher Rankl transcripts were
identified in splenic T lymphocytes in Apoe-/- mice, and their levels were
reduced in Apoe-/- ;D5-/- mice. When analyzed by micro-computed tomography (uCT),
atherosclerotic plaque calcification was identified in six out of eight Apoe-/-
mice, whereas only one out of eight Apoe-/- ;D5-/- mice developed plaque
calcification after 12 weeks of HFD. However, following 18 weeks of HFD
challenge, all of Apoe-/- and Apoe-/- ;D5-/- animals developed atherosclerotic
plaque calcification. Likewise, atherosclerotic lesion sizes were site
specifically reduced in the aortic arch of Apoe-/- ;D5-/- mice at initial stage
of atherosclerosis and this effect was diminished as atherosclerosis proceeded to
a more advanced stage. Our data suggest that deletion of the RANKL D5 enhancer
delays the progression of atherosclerotic plaque development and plaque
calcification in hypercholesterolemic mice. This work provides important insight
into RANKL's regulatory role in atherosclerosis. J. Cell. Biochem. 118: 4240
4253, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419522
TI - A general empirical model for renal drug handling in pharmacokinetic analyses.
AB - Dose adjustment in renal insufficiency is generally based on the assumption that
renal drug clearance is related linearly to glomerular filtration rate. The
theory underpinning this model is the intact nephron hypothesis, which says that
impaired renal function is caused by a reduction in the number of complete
(intact) nephrons. The purpose of the present commentary is to propose a general
empirical model for renal drug handling. We will explore models for renal
function under two scenarios: one that aligns with the intact nephron hypothesis,
and one that relaxes the assumptions of this hypothesis. We propose that a
nonlinear, non-intact nephron model will allow for differences in renal drug
handling, while incorporating the intact nephron hypothesis model as a special
case.
PMID- 28419523
TI - Multiple imputation to evaluate the impact of an assay change in national
surveys.
AB - National health surveys, such as the National Health and Nutrition Examination
Survey, are used to monitor trends of nutritional biomarkers. These surveys try
to maintain the same biomarker assay over time, but there are a variety of
reasons why the assay may change. In these cases, it is important to evaluate the
potential impact of a change so that any observed fluctuations in concentrations
over time are not confounded by changes in the assay. To this end, a subset of
stored specimens previously analyzed with the old assay is retested using the new
assay. These paired data are used to estimate an adjustment equation, which is
then used to 'adjust' all the old assay results and convert them into
'equivalent' units of the new assay. In this paper, we present a new way of
approaching this problem using modern statistical methods designed for missing
data. Using simulations, we compare the proposed multiple imputation approach
with the adjustment equation approach currently in use. We also compare these
approaches using real National Health and Nutrition Examination Survey data for
25-hydroxyvitamin D. Published 2017. This article is a U.S. Government work and
is in the public domain in the USA.
PMID- 28419524
TI - Fibronectin From Oviductal Cells Fluctuates During the Estrous Cycle and
Contributes to Sperm-Oviduct Interaction in Cattle.
AB - During the passage of sperm through the oviduct, spermatozoa bind to the
oviductal epithelium and form the oviductal reservoir. This interaction keeps the
fertilizing capacity of sperm until ovulation-associated signals induce sperm
release from the oviductal epithelium, allowing the transit of spermatozoa to the
fertilization site. Fibronectin is a glycoprotein from the extracellular matrix
that binds to alpha5beta1 receptors. Fibronectin has been found to be expressed
in the oviduct, whereas alpha5beta1 has been found to be expressed in the sperm
of different species. Fibronectin is involved through alpha5beta1 in sperm
functions. The aim of this work was to study the participation of oviductal
fibronectin in the regulation of the sperm-oviduct interaction in cattle. We
found that oviductal epithelial cells differentially expressed all mRNA splice
variants of fibronectin during the estrous cycle. Fibronectin was localized in
the apical region of oviductal epithelial cells and fibronectin levels in the
oviductal fluid fluctuated during the estrous cycle. Also, bovine spermatozoa
expressed alpha5beta1. Using in vitro sperm-oviduct co-cultures, we found that
spermatozoa were attached to the oviductal epithelium through alpha5beta1. The
incubation of co-cultures with fibronectin induced sperm release from the
oviductal cells through alpha5beta1. The sperm population released from oviductal
cells by fibronectin was enriched in motile and capacitated spermatozoa. Based on
our in vitro culture system results, we propose that fibronectin and alpha5beta1
are involved in the sperm-oviduct interaction. Also, an increase in fibronectin
levels in the oviductal fluid during the pre-ovulatory period may promote sperm
release from the oviductal epithelium in cattle. J. Cell. Biochem. 118: 4095
4108, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419525
TI - Method comparison and generation of plasma biochemistry RIs for the White
rhinoceros on a point-of-care and wet chemistry analyzer.
AB - BACKGROUND: Plasma biochemistry analysis may aid the management of White
rhinoceros with poaching or other injuries. Analyzer- and species-specific RIs
are necessary to evaluate health status and identify abnormalities. OBJECTIVES:
The purpose of the study was to perform a comparison study between the IDEXX
VetTest and Roche Cobas Integra 400 Plus, and to generate analyzer-specific RIs
for White rhinoceros according to published guidelines. METHODS: Comparison was
carried out using White rhinoceros plasma samples from healthy and diseased
animals. Reference intervals for albumin, ALT, AST, CK, creatinine, GGT,
globulins, glucose, phosphorus, total proteins, and urea were determined from a
sample group of chemically immobilized healthy adult White rhinoceros from the
Kruger National Park, South Africa. RESULTS: There was a significant analytic
bias for all analytes between the 2 analyzers. Results for glucose and total
protein were clinically equivalent based on total allowable error limits.
Reference intervals were generated from 51 individuals (26 male, 25 female) for
all analytes except ALT on the VetTest. DISCUSSION: The type, direction, and
magnitude of bias between the VetTest and Cobas appeared to be species- and
analyzer-specific, when compared to other studies. These measures of bias may be
used for comparability testing. Reference intervals for total proteins (VetTest
77-108 g/L, Cobas 77-110 g/L) and globulins (VetTest 47-79 g/L, Cobas 51-87 g/L)
were high compared to other uneven-toed ungulates. CONCLUSION: Plasma samples
from White rhinoceros can be evaluated on both the VetTest and Cobas. Results
from this study will aid conservation efforts directed toward this species.
PMID- 28419526
TI - Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and
Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve
the Survival Rate of Septic Mice.
AB - Sepsis is one of the most challenging health problems worldwide. Our previous
study showed that chronic schistosoma japonica (SJ) infection might increase
serum anti-inflammatory factors to play a protective role, thus improving the
survival rate of septic mice. Further research revealed that SJ infection
promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS
induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-beta1
expression; inhibited TNF-alpha and iNOS expression; and blocked the effect of
LPS-promoted TNF-alpha and iNOS expression. Furthermore, adoptive transfer of ex
vivo programed M2 macrophages significantly increased the survival rate of septic
mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played
the same role as worm infection but had no impact on M1 macrophages. SEA reduced
LPS-induced TNF-alpha and iNOS expression, decreased the inhibitory effect of LPS
on IL-10 and TGF-beta1 expression, increased STAT6 phosphorylation, and up
regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K
inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be
reduced. Therefore, worm infection has a protective effect in septic mice in
which SEA may play a key role via the STAT6 and PI3K pathways. This finding may
provide a favorable solution for the treatment of sepsis, especially early cases.
J. Cell. Biochem. 118: 4230-4239, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419527
TI - The "rectosigmoid brake": Review of an emerging neuromodulation target for
colorectal functional disorders.
AB - The regulation of gastrointestinal motility encompasses several overlapping
mechanisms including highly regulated and coordinated neurohormonal circuits.
Various feedback mechanisms or "brakes" have been proposed. While duodenal,
jejunal, and ileal brakes are well described, a putative distal colonic brake is
less well defined. Despite the high prevalence of colonic motility disorders,
there is little knowledge of colonic motility owing to difficulties with organ
access and technical difficulties in recording detailed motor patterns along its
entire length. The motility of the colon is not under voluntary control. A wide
range of motor patterns is seen, with long intervals of intestinal quiescence
between them. In addition, the use of traditional manometric catheters to record
contractile activity of the colon has been limited by the low number of widely
spaced sensors, which has resulted in the misinterpretation of colonic motor
patterns. The recent advent of high-resolution (HR) manometry is revolutionising
the understanding of gastrointestinal motor patterns. It has now been observed
that the most common motor patterns in the colon are repetitive two to six cycles
per minute (cpm) propagating events in the distal colon. These motor patterns are
prominent soon after a meal, originate most frequently in the rectosigmoid
region, and travel in the retrograde direction. The distal prominence and the
origin of these motor patterns raise the possibility of them serving as a braking
mechanism, or the "rectosigmoid brake," to limit rectal filling. This review aims
to describe what is known about the "rectosigmoid brake," including its
physiological and clinical significance and potential therapeutic applications.
PMID- 28419528
TI - An updated synthesis of [11 C]carfentanil for positron emission tomography (PET)
imaging of the MU-opioid receptor.
AB - [11 C]Carfentanil ([11 C]CFN) is a selective radiotracer for in vivo positron
emission tomography imaging studies of the MU-opioid system that, in our
laboratories, is synthesized by methylation of the corresponding carboxylate
precursor with [11 C]MeOTf, and purified using a C2 solid-phase extraction
cartridge. Changes in the commercial availability of common C2 cartridges have
necessitated future proofing the synthesis of [11 C]CFN to maintain reliable
delivery of the radiotracer for clinical imaging studies. An updated synthesis of
[11 C]CFN is reported that replaces a now obsolete purification cartridge with a
new commercially available version and also substitutes the organic solvents used
in traditional production methods with ethanol.
PMID- 28419529
TI - Critical discourse analysis of social justice in nursing's foundational
documents.
AB - OBJECTIVE: Social inequities threaten the health of the global population. A
superficial acknowledgement of social justice by nursing's foundational documents
may limit the degree to which nurses view injustice as relevant to nursing
practice and education. The purpose was to examine conceptualizations of social
justice and connections to broader contexts in the most recent editions. DESIGN:
Critical discourse analysis examines and uncovers dynamics related to power,
language, and inequality within the American Nurses Association's Code of Ethics,
Scope and Standards of Practice, and Social Policy Statement. RESULTS: This
analysis found ongoing inconsistencies in conceptualizations of social justice.
Although the Code of Ethics integrates concepts related to social justice far
more than the other two, tension between professionalism and social change
emerges. The discourse of professionalism renders interrelated cultural, social,
economic, historical, and political contexts nearly invisible. CONCLUSION:
Greater consistency would provide a clearer path for nurses to mobilize and
engage in the courageous work necessary to address social injustice. These
findings also call for an examination of how nurses can critique and use the
power and privilege of professionalism to amplify the connection between social
institutions and health equity in nursing education, practice, and policy
development.
PMID- 28419530
TI - Differential expression profile analysis of PSTK-regulated mRNAs in podocytes.
AB - This study aimed to elucidate the precise mechanisms underlying the protective
effects of phosphoseryl-tRNA kinase (PSTK) against cisplatin-induced podocyte
injury. PSTK overexpression and knockdown vectors were generated and transfected
into MPC-5. PSTK levels were measured, and transcriptome sequencing was
conducted. Differential expression analysis was performed to identify mRNAs that
were positively and negatively correlated with PSTK. We selected 10 candidate
genes identified via real-time quantitative polymerase chain reaction and Western
blotting for further analysis. As expected, PSTK levels were significantly higher
in PSTK-overexpressing podocytes and significantly lower in PSTK-knockdown
podocytes. PSTK overexpression resulted in the upregulation of 122 genes and
downregulation of 372 genes in podocytes. On the other hand, PSTK knockdown
resulted in the upregulation of 231 genes and downregulation of 445 genes.
Furthermore, the analysis revealed that 11 genes were positively correlated with
PSTK, whereas 20 genes were negatively correlated with PSTK. The obtained PSTK
regulated genes were primarily involved in molecular function, biological
process, and cellular component, as well as the angiogenesis pathway. Wnt family
member 10A levels were significantly higher after PSTK overexpression, but were
significantly lower after PSTK knockdown. In addition, Na(+)/K(+) ATPase subunit
alpha-2 and matrix metalloproteinase 9 levels were significantly downregulated
after PSTK overexpression, but significantly upregulated upon PSTK knockdown.
Cell proliferation was significantly increased upon PSTK overexpression, but
significantly decreased upon PSTK suppression. The results of this study not only
identified several significant PSTK-regulated genes for further validation, but
also provided insights into the mechanisms underlying the protective effects of
PSTK on podocytes. This article is protected by copyright. All rights reserved.
PMID- 28419531
TI - Urinary incontinence and hydration: A population-based analysis.
AB - AIMS: To determine if there is an association between urinary incontinence (UI)
and an objective measure of hydration status in men and women in a nationwide,
population-based sample. METHODS: We utilized data from the 2009 to 2010 and 2011
to 2012 National Health and Nutrition Examination Surveys (NHANES), cross
sectional surveys of the US non-institutionalized population. Our primary outcome
was moderate/severe UI measured using a validated scale. Our exposure of interest
was hydration status. Urine osmolality >= 800 mOsm/kg defined dehydration versus
adequate hydration (<800 mOsm/kg). We included men and women >= 20 years who had
both UI and urine osmolality data. Using multivariable models, we controlled for
age, race/ethnicity, BMI, chronic kidney disease, the interaction of age with
osmolality, and hysterectomy (women only). RESULTS: Among the 11 482 total
subjects, 9497 (83%-4882 men and 4615 women) had both UI and urine osmolality
data. Compared to women, men were less likely to report UI (5.9% vs 18.9%; P <
0.001) and more likely to be dehydrated (33.4% vs 24.0%; P < 0.001). In bivariate
analysis, men and women who were dehydrated had less UI than men with adequate
hydration (men: 3.5% vs 7.6%; P < 0.001; women: 16.3% vs 20.0%; P = 0.02);
however, dehydration was not associated with UI in men (OR 0.2, 95% CI 0.6-1.0)
or in women (OR 0.8, 95% CI 0.4-1.5) in multivariable models. CONCLUSIONS:
Hydration status as defined by urine osmolality was not associated with moderate
to severe urinary incontinence in men or women.
PMID- 28419532
TI - ICS Educational Module: Electromyography in the assessment and therapy of lower
urinary tract dysfunction in adults.
AB - AIM: To present the teaching module "Electromyography in the assessment and
therapy of lower urinary tract dysfunction in adults." This teaching module
embodies a presentation, in combination with this manuscript. This manuscript
serves as a scientific background review; the evidence base made available on ICS
website to summarize current knowledge and recommendations. METHODS: This review
has been prepared by a Working Group of The ICS Urodynamics Committee. The
methodology used included comprehensive literature review, consensus formation by
the members of the Working Group, and review by members of the ICS Urodynamics
Committee core panel. RESULTS: Electromyography (EMG) is a method to record
spontaneous or artificially induced electrical activity of the nerve-muscle unit
or to test nerve conductivity. EMG of the anal sphincter using surface electrode
is most widely used screening technique to detect detrusor-sphincter dyssynergia
in urology. It is non-invasive and easy to perform. EMG methods using needle
electrodes are reserved for diagnostics in well selected group of mainly
neurogenic patients. These methods require expertise in the field of general EMG
and are usually performed by neurologist and neuro-physiologist. The evidence in
many aspects of use of EMG in urology remains sparse. CONCLUSIONS: Currently EMG
methods rarely play a decision making role in selecting proper treatment of lower
urinary tract dysfunction. With the current efforts to improve phenotyping of
these patients in order to provide individualized treatment, the role of EMG
could increase.
PMID- 28419533
TI - A new approach for radiosynoviorthesis: A dose-optimized planning method based on
Monte Carlo simulation and synovial measurement using 3D slicer and MRI.
AB - PURPOSE: Recently, there has been a growing interest in a methodology for dose
planning in radiosynoviorthesis to substitute fixed activity. Clinical practice
based on fixed activity frequently does not embrace radiopharmaceutical dose
optimization in patients. The aim of this paper is to propose and discuss a dose
planning methodology considering the radiological findings of interest obtained
by three-dimensional magnetic resonance imaging combined with Monte Carlo
simulation in radiosynoviorthesis treatment applied to hemophilic arthropathy.
METHOD: The parameters analyzed were: surface area of the synovial membrane
(synovial size), synovial thickness and joint effusion obtained by 3D MRI of nine
knees from nine patients on a SIEMENS AVANTO 1.5 T scanner using a knee coil. The
3D Slicer software performed both the semiautomatic segmentation and quantitation
of these radiological findings. A Lucite phantom 3D MRI validated the
quantitation methodology. The study used Monte Carlo N-Particle eXtended code
version 2.6 for calculating the S-values required to set up the injected activity
to deliver a 100 Gy absorbed dose at a determined synovial thickness. The
radionuclides assessed were: 90Y, 32P, 188Re, 186Re, 153Sm, and 177Lu, and the
present study shows their effective treatment ranges. RESULT: The quantitation
methodology was successfully tested, with an error below 5% for different
materials. S-values calculated could provide data on the activity to be injected
into the joint, considering no extra-articular leakage from joint cavity.
Calculation of effective treatment range could assist with the therapeutic
decision, with an optimized protocol for dose prescription in RSO. CONCLUSION:
Using 3D Slicer software, this study focused on segmentation and quantitation of
radiological features such as joint effusion, synovial size, and thickness, all
obtained by 3D MRI in patients' knees with hemophilic arthropathy. The
combination of synovial size and thickness with the parameters obtained by Monte
Carlo simulation such as effective treatment range and S-value, from which is
calculated the injected activity, could be used for treatment planning in RSO.
Data from this methodology could be a potential aid to clinical decision making
by selecting the most suitable radionuclide; justifying the procedure,
fractioning the dose, and the calculated injected activity for children and
adolescents, considering both the synovial size and thickness.
PMID- 28419534
TI - Endocrine Imbalance Associated With Proteome Changes in Diabetes.
AB - The dynamics of cellular metabolism involves rapid interactions between proteins
and nucleic acids, proteins and proteins, and signaling. These involve the
interactions with respect to the sulfur bond, noncovalent electrostatic
interactions, protein structure stabilization and protein-ligand binding, weak
electrostatic interactions in proteins, oxygen radicals that initiate a change in
conformation and a chain of events. We review a development in molecular medicine
that is a very promising work in progress. We also review the current and future
research methods involving mitochondria. Long-term effects of diabetes include
glycation of proteins, for example, glycohemoglobin (HbA1c), increased risk of
cardiovascular diseases, atherosclerosis, retinopathy, nephropathy, and
neurological dysfunctions. Tissues are exposed to significant quantities of
highly reactive chemical species including nitric oxide * NO and reactive oxygen
species ROS over months to years, to an extent generated by mitochondrial
activities. The reactions of * NO can be broadly discussed with reference to
three main processes which control their fate in biological systems: (1)
diffusion and intra-cellular consumption; (2) autooxidation to form nitrous
anhydride N2 O3 ; and (3) reaction with superoxide O2* - to form peroxynitrite
ONOO-. Reactive nitrogen species produced by macrophages and neutrophils in the
interstitial space, with emphasis on * NO, N2 O3 , ONOO-, and nitrogen dioxide
radicals * NO2 generate protein and DNA damage. Serum thiol (-SH) groups act as
an important extracellular scavenger of peroxides and are therefore helpful in
protecting the surrounding tissues. The events described here are a homeostatic
endocrine imbalance that is associated with proteostasis. The advances we have
seen in untangling this web of interactions are sure to continue at a
breathtaking pace. J. Cell. Biochem. 118: 3569-3576, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28419535
TI - Enhanced Entrapment and Improved in Vitro Controlled Release of N-Acetyl Cysteine
in Hybrid PLGA/Lecithin Nanoparticles Prepared Using a Nanoprecipitation/Self
Assembly Method.
AB - To enhance the in vitro controlled release of N-acetyl cysteine (NAC), hybrid
nanoparticles (NPs) consisting of a poly(lactide-co-glycolide) (PLGA) hydrophobic
core and a soybean lecithin mono-layer coat were prepared. Hybrid NPs were
synthesized using a nanoprecipitation combined with self-assembly method. To
characterize prepared NPs, zeta potential, diameter size, surface morphology,
disparity, and lipid coating of hybrid NPs were detrmined using dynamic light
scattering, scanning electron microscope and Fourier transform infrared
spectroscopy techniques. High-performance liquid chromatography was employed to
evaluate drug loading yield and encapsulation efficiency and in vitro drug
release of prepared NPs. The cytotoxicity of hybrid NPs was assayed on normal
L929 alveolar epithelial cells using MTT method. Prepared NPs were found to
disperse as individual NPs with a well-defined spherical shape. The hydrodynamic
diameter and surface charge of NAC-loaded hybrid NPs were 81.8 +/- 1.3 nm and
33.1 +/- 2.1 mV, respectively. Drug loading yield and encapsulation efficiency of
NAC-loaded hybrid NPs were found to be 38 +/- 2.1% and 67 +/- 5.7%, respectively.
Prepared hybrid NPs showed no significant cytotoxicity against normal alveolar
cells. Our data suggest that the hybrid PLGA-lecithin NPs may be An efficient
controlled release drug delivery system for NAC. J. Cell. Biochem. 118: 4203
4209, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419536
TI - Characteristics and related factors of Japanese mothers who have faced
difficulties with childrearing.
AB - OBJECTIVE: To identify characteristics of mothers who face difficulties with
childrearing. DESIGN AND SAMPLE: Cross-sectional study. During 2014, 221 mothers
and 248 children living in City A within the Tokyo metropolis were registered as
requiring help with childrearing. Nursing records of 205 mothers (92.8%) and
their 227 children (91.5%) were available. We excluded 29 mothers and children
owing to incomplete data for a final sample of 176 mothers (79.6%) and 198
children (79.8%). MEASURES: Difficulties with childrearing were assessed by self
reported questionnaires at the newborn child's 4-month health checkups. Data on
maternal and child variables were collected from nursing records. RESULTS: The
"Difficulties group" included 59 mothers (35.4%) and their 70 children. Logistic
regression analysis showed that mothers who were aged 40 years or older, who had
a total score on the Edinburgh Postnatal Depression Scale of 9 or greater, who
used more child-care support services, and who were monitored more frequently by
public health nurses had a high risk of facing difficulties with childrearing.
CONCLUSIONS: Periodic monitoring by PHNs is a key strategy to improve the impact
of the difficulties of childrearing for mothers of yoshien jido and their
children.
PMID- 28419537
TI - Electromagnetic tracking for femoral derotation osteotomy-an in vivo study.
AB - Femoral derotation osteotomy delivers good to excellent results in the treatment
of rotational gait abnormalities and especially in internal rotation gait. The
outcome of the procedure has been evaluated in numerous short- and long-term
studies. Although reasons for recurrence and over-/under-correction have been
unveiled in earlier studies the mechanisms are still not fully understood. False
intra-operative assessment of the derotation angle may contribute to imprecise
outcomes. In a recent saw-bone study we evaluated an electromagnetic tracking
system in comparison to conventional goniometer measurement and a CT reference
measurement and found it to be extremely accurate, whereas the use of a
conventional goniometer for derotation measurement showed a high inter- and intra
rater variability. The current study evaluates the electromagnetic tracking
system for continuous intra-operative derotation control under real OR
conditions. Adults (age: 18-40 years) with the diagnosis of internal rotation
gait, independent of the underling pathology, undergoing a supracondylar
deroation osteotomy were included. A rotational CT scan was conducted before and
in close proximity after surgery and the difference served as reference for the
electromagnetic tracking results. The results showed a mean deviation of 2.6
degrees (1.2-5.5 degrees ) in comparison to the reference measurement of the pre
and post-operative CT scans. The system proved to be stable under OR conditions
with a good usability and a small technical footprint. Electromagnetic tracking
delivers a precise, reliable, and independent assessment of intra-operative
derotation angles in femoral derotation osteotomies. (c) 2017 Orthopaedic
Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2652-2657,
2017.
PMID- 28419538
TI - Receiving early information and trusting Swedish child health centre nurses
increased parents' willingness to vaccinate against rotavirus infections.
AB - AIM: Rotavirus vaccines are effective against severe infections, but have a
modest impact on mortality in high-income countries. Parental knowledge and
attitudes towards vaccines are crucial for high vaccination coverage. This study
aimed to identify why parents refused to let their infant have the vaccination or
were unsure. METHODS: This cross-sectional study was based on 1,063
questionnaires completed by the parents of newborn children in 2014. Stepwise
logistic regression was used to identify the main predictors. RESULTS: Most (81%)
parents intended to vaccinate their child against the rotavirus, while 19% were
unwilling or uncertain. Parents with less education and children up to five weeks
of age were more likely to be unwilling or uncertain about vaccinating their
child. Factors associated with a refusal or uncertainty about vaccinating were
not having enough information about the vaccine, no intention of accepting other
vaccines, paying little heed to the child health nurses' recommendations,
thinking that the rotavirus was not a serious illness and not believing that the
vaccine provided protection against serious forms of gastroenteritis. CONCLUSION:
Early information, extra information for parents with less education and close
positive relationships between parents and child health nurses were important
factors in high rotavirus vaccination rates.
PMID- 28419539
TI - PD-L1 expression in extrahepatic cholangiocarcinoma.
AB - AIMS: To investigate the expression of the programmed cell death 1 (PD-1)
receptor-programmed cell death ligand 1 (PD-L1) pathway and the
clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA).
METHODS AND RESULTS: Tissue samples from patients with eCCA [n = 69; perihilar
cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical
resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and
CD163 expression, and correlations with clinicopathological characteristics,
including survival data, were determined. PD-L1 was found on both tumour cells of
eCCA (8/69, 11.6%) and tumour-associated macrophages (21/69, 30.4%). Significant
correlations of PD-L1 expression on cancer cells with venous invasion (P = 0.031)
and poor differentiation of the tumour (P = 0.048) were observed. In 19 of 69
(27.5%) samples, tumour-infiltrating lymphocytes (TILs) expressed PD-1, whereas
infiltration with CD3-positive and CD163-positive cells was found in 63 of 69
(91.3%) and 68 of 69 (98.6%) cases, respectively. The presence of fewer than five
CD3-positive cells per high-power field was significantly correlated with poorer
differentiation (P = 0.015) and venous invasion (P < 0.001) of CCA. PD-L1
expression was not correlated with patient survival, but PD-L1 expression on
tumour cells combined with low infiltration of CD3-positive TILs was associated
with an unfavourable outcome (P = 0.027). CONCLUSION: Only a small number of eCCA
patients are PD-L1-positive, which might be important for future application of
PD-1/PD-L1-targeted immune-modulating therapy in these patients. A small subgroup
of eCCAs with PD-L1 expression and low lymphocytic infiltration showed more
invasive growth and worse overall survival.
PMID- 28419540
TI - Deep Granuloma Annulare Mimicking Inflamed Cysts in a Teenager.
AB - We describe deep granuloma annulare (DGA) of the forehead mimicking inflamed
cysts. Reactive inflammation and sterile purulent drainage may be an
underrecognized feature of DGA.
PMID- 28419541
TI - When should active surveillance for prostate cancer stop if no progression is
detected?
AB - BACKGROUND: A significant proportion of screen-detected men with prostate cancer
may be overdiagnosed. Active Surveillance (AS) has emerged as a way to mitigate
this problem, by delaying treatment of men, who are at low-risk until this
becomes necessary. However, it is not known after how much time or biopsy rounds
should patients stop AS and transition to conservative management (CM), if no
progression is detected. METHODS: We used a microsimulation model with natural
history of prostate cancer based on ERSPC and SEER data. We modeled referral to
treatment while in AS, based on Johns Hopkins treatment-free survival data. We
projected lifetime costs and effects of AS (and radical treatment, if progression
is detected) under different biopsy follow-up schedules compared to CM, where
radical treatment only occurs when men would be clinically diagnosed in absence
of screening. RESULTS: For men with low-risk disease in younger age groups (55
65), AS is cost-effective for up to 7 yearly biopsy rounds. For men older than
65, even one biopsy round results in quality adjusted life years (QALYs) lost,
though it may result in QALYs gained for men without previous screening. For men
with intermediate-risk disease AS is cost-effective even for men in 65-75 age
group. CONCLUSIONS: The benefit of AS when compared to CM is strongly dependent
on life expectancy and disease risk. Clinicians should take this into account
when selecting men to AS, deciding on biopsy frequency and when to stop AS
surveillance rounds and transition to CM.
PMID- 28419542
TI - Effect of nanosilver on metabolism in rainbow trout (Oncorhynchus mykiss): An
investigation using different respirometric approaches.
AB - Nanosilver (nAg) has been incorporated into many consumer products, including
clothing and washing machines, because of its antimicrobial properties.
Consequently, the potential for its release into aquatic environments is of
significant concern. Documented toxic effects on fish include altered gene
expression, gill damage, and impaired gas exchange, as well as mortality at high
nAg concentrations. The present study reports the effects of nAg on the
metabolism of rainbow trout (Oncorhynchus mykiss). Fish were exposed to
environmentally relevant concentrations (0.28 +/- 0.02 MUg/L) and higher (47.60
+/- 5.13 MUg/L) for 28 d, after which their standard metabolic rate (SMR), forced
maximum metabolic rate (MMRf ), and spontaneous maximum metabolic rate (MMRs )
were measured. There was no effect observed in SMR, MMRf , or MMRs , suggesting
that nAg is unlikely to directly affect fish metabolism. On average, MMRs tended
to be greater than MMRf , and most MMRs occurred when room lighting increased.
The timing of MMRf chase protocols was found to affect both MMRf and SMR
estimates, in that chasing fish before respirometric experiments caused higher
MMRf estimates and lower SMR estimates. Although compounded effects involving nAg
and other environmental stressors remain unknown, the present study indicates
that the tested range of nAg is unlikely to constrain fish metabolism. Environ
Toxicol Chem 2017;36:2722-2729. (c) 2017 SETAC.
PMID- 28419543
TI - Aging does not alter tendon mechanical properties during homeostasis, but does
impair flexor tendon healing.
AB - Aging is an important factor in disrupted homeostasis of many tissues. While an
increased incidence of tendinopathy and tendon rupture are observed with aging,
it is unclear whether this is due to progressive changes in tendon cell function
and mechanics over time, or an impaired repair reaction from aged tendons in
response to insult or injury. In the present study, we examined changes in the
mechanical properties of Flexor Digitorum Longus (FDL), Flexor Carpi Ulnaris
(FCU), and tail fascicles in both male and female C57Bl/6 mice between 3 and 27
months of age to better understand the effects of sex and age on tendon
homeostasis. No change in max load at failure was observed in any group over the
course of aging, although there were significant decreases in toe and linear
stiffness in female mice from 3 to 15 months, and 3 to 27 months. No changes in
cell proliferation were observed with aging, although an observable decrease in
cellularity occurred in 31-month old tendons. Given that aging did not
dramatically alter tendon mechanical homeostasis we hypothesized that a
disruption in tendon homeostasis, via acute injury would result in an impaired
healing response. Significant decreases in max load, stiffness, and yield load
were observed in repairs of 22-month old mice, relative to 4-month old mice. No
changes in cell proliferation were observed between young and aged, however, a
dramatic loss of bridging collagen extracellular matrix was observed in aged
repairs suggest that matrix production, but not cell proliferation leads to
impaired tendon healing with aging. Results (c) 2017 Orthopaedic Research
Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2716-2724, 2017.
PMID- 28419544
TI - Adults born preterm: a review of general health and system-specific outcomes.
AB - : In this review of 126 publications, we report that an overwhelming majority of
adults born at preterm gestations remain healthy and well. However, a small, but
a significant fraction of them remain at higher risk for neurological,
personality and behavioural abnormalities, cardio-pulmonary functional
limitations, systemic hypertension and metabolic syndrome compared to their term
born counterparts. The magnitude of increased risk differed across organ systems
and varied across reports. The risks were proportional to the degree of
prematurity at birth and seemed to occur more frequently among preterm infants
born in the final two decades of the 20th century and later. These findings have
considerable public health and clinical practice relevance. CONCLUSION: Preterm
birth needs to be considered a chronic condition, with a slight increase in the
risk for long-term morbidities among adults born preterm. Therefore, obtaining a
history of gestational age and weight at birth should be a routine part of care
for patients of all age groups.
PMID- 28419545
TI - Intermolecular Interactions Between DMalpha and DMbeta Proteins in BuLA-DM
Complex of Water Buffalo Bubalus bubalis.
AB - The major histocompatibility complex (MHC) with its three classes represents a
cluster of tightly linked genes with defined immunological and non-immunological
functions. The DM, a MHC class II molecule is formed by the non-covalent
association of DMalpha and DMbeta chains. It binds with the processed peptide
antigens and presents them to T lymphocytes, thereby triggering the immune
responses. Startlingly, the expression pattern and structural organization of
DMalpha and DMbeta proteins in buffalo remains undefined. We isolated and
purified the DMalpha and DMbeta proteins from Bubalus bubalis using gel
filtration chromatography. Employing western blotting and immunohistochemistry,
highest expression of these proteins was observed in spleen and were later
localized in the cytoplasm. We modelled 3D structures of the proteins and
assessed the binding interface of BuLA-DM docked complex. In the process, we
uncovered 9 DMalpha and 8 DMbeta specific residues participating in the formation
of BuLA-DM complex. Our work demonstrated active participation of the critical
amino acid residues engaged in the formation of BuLA-DM complex facilitating
deeper understanding on the structure-function relationship of these proteins. J.
Cell. Biochem. 118: 4254-4266, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419546
TI - Connexin43 and Runx2 Interact to Affect Cortical Bone Geometry, Skeletal
Development, and Osteoblast and Osteoclast Function.
AB - The coupling of osteoblasts and osteocytes by connexin43 (Cx43) gap junctions
permits the sharing of second messengers that coordinate bone cell function and
cortical bone acquisition. However, details of how Cx43 converts shared second
messengers into signals that converge onto essential osteogenic processes are
incomplete. Here, we use in vitro and in vivo methods to show that Cx43 and Runx2
functionally interact to regulate osteoblast gene expression and proliferation,
ultimately affecting cortical bone properties. Using compound hemizygous mice for
the Gja1 (Cx43) and Runx2 genes, we observed a skeletal phenotype not visible in
wild-type or singly hemizygous animals. Cortical bone analysis by micro-computed
tomography (MUCT) revealed that 8-week-old male, compound Gja1+/- Runx2+/- mice
have a marked increase in cross-sectional area, endosteal and periosteal bone
perimeter, and an increase in porosity compared to controls. These compound
Gja1+/- Runx2+/- mice closely approximate the cortical bone phenotypes seen in
osteoblast-specific Gja1-conditional knockout models. Furthermore, MUCT analysis
of skulls revealed an altered interparietal bone geometry in compound
hemizygotes. Consistent with this finding, Alizarin red/Alcian blue staining of 2
day-old Gja1+/- Runx2+/- neonates showed a hypomorphic interparietal bone, an
exacerbation of the open fontanelles, and a further reduction in the hypoplastic
clavicles compared to Runx2+/- neonates. Expression of osteoblast genes,
including osteocalcin, osterix, periostin, and Hsp47, was markedly reduced in
tibial RNA extracts from compound hemizygous mice, and osteoblasts from compound
hemizygous mice exhibited increased proliferative capacity. Further, the reduced
osteocalcin expression and hyperproliferative nature of osteoblasts from Cx43
deficient mice was rescued by Runx2 expression. In summary, these findings
provide evidence that Cx43 and Runx2 functionally intersect in vivo to regulate
cortical bone properties and affect osteoblast differentiation and proliferation,
and likely contributes to aspects of the skeletal phenotype of Cx43 conditional
knockout mice. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28419549
TI - Erratum.
PMID- 28419547
TI - Perinatal DNA Methylation at CDKN2A Is Associated With Offspring Bone Mass:
Findings From the Southampton Women's Survey.
AB - Poor intrauterine and childhood growth has been linked with the risk of
osteoporosis in later life, a relationship that may in part be mediated through
altered epigenetic regulation of genes. We previously identified a region within
the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at
which differential DNA methylation at birth showed correlations with offspring
adiposity. Given the common lineage of adipocytes and osteoblasts, we
investigated the relationship between perinatal CDKN2A methylation and bone mass
at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the
methylation status of the 9 CpGs within this region in umbilical cord samples
from discovery (n = 332) and replication (n = 337) cohorts of children from the
Southampton Women's Survey, whose bone mass was assessed by dual-energy X-ray
absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between
perinatal CDKN2A methylation and whole-body minus head bone area (BA), bone
mineral content (BMC), and areal bone mineral density (BMD). This was confirmed
in replication and combined data sets (all p < 0.01), with each 10% increase in
methylation being associated with a decrease in BMC of 4 to 9 g at age 4 years (p
<= 0.001). Relationships were similar with 6-year bone mass. Functional
investigation of the differentially methylated region in the SaOS-2 osteosarcoma
cell line showed that transcription factors bound to the identified CpGs in a
methylation-specific manner and that CpG mutagenesis modulated ANRIL expression.
In conclusion, perinatal methylation at CDKN2A is associated with childhood bone
development and has significance for cell function. (c) 2017 American Society for
Bone and Mineral Research.
PMID- 28419548
TI - Detection of prostate cancer-specific transcripts in extracellular vesicles
isolated from post-DRE urine.
AB - BACKGROUND: The measurement of gene expression in post-digital rectal examination
(DRE) urine specimens provides a non-invasive method to determine a patient's
risk of prostate cancer. Many currently available assays use whole urine or cell
pellets for the analysis of prostate cancer-associated genes, although the use of
extracellular vesicles (EVs) has also recently been of interest. We investigated
the expression of prostate-, kidney-, and bladder-specific transcripts and known
prostate cancer biomarkers in urine EVs. METHODS: Cell pellets and EVs were
recovered from post-DRE urine specimens, with the total RNA yield and quality
determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated
transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RESULTS:
RNA was more consistently recovered from the urine EV specimens, with over 80% of
the patients demonstrating higher RNA yields in the EV fraction as compared to
urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher
than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE
urine EVs indicated that prostate-specific transcripts were more abundant than
kidney- or bladder-specific transcripts. Additionally, patients with prostate
cancer had significantly higher levels of the prostate cancer-associated genes
PCA3 and ERG. CONCLUSIONS: Post-DRE urine EVs are a viable source of prostate
derived RNAs for biomarker discovery and prostate cancer status can be
distinguished from analysis of these specimens. Continued analysis of urine EVs
offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer
detection.
PMID- 28419550
TI - Urban primate ranging patterns: GPS-collar deployments for Macaca fascicularis
and M. sylvanus.
AB - The global increase in urbanization is leading to heavier interface between
humans and wildlife. Within these anthropogenic landscapes, little is known about
ranging patterns, particularly with regard to urban primates. Here we present the
results of the first long-term deployment of multiple GPS collars on two species
of macaques to investigate the impacts of urbanization on urban primate ranging
patterns in Singapore and Gibraltar. Collars data acquisition were excellent with
respect to the amount, quality, and accuracy of data collected; however, remote
connectivity and drop-off functionality was poor across all deployments. Analyses
highlighted high variability in ranging patterns between individuals within each
species that aligned with access to human food resources and patterns of tourism.
Individuals from troops with less access to human food had much larger home,
core, and day ranges relative to those with regular provisioning or raiding
opportunities. Almost no temporal range overlap was observed between any focal
individuals at either site and spatial overlap was low for all but two troops at
each site. We found no relationship between anthropogenic schedules and changes
in ranging patterns. Significant seasonal variation existed for daily path length
and day range size for both the Singapore long-tailed and the Gibraltar Barbary
macaques, with long-tailed macaques increasing their range during the equatorial
monsoon season and Barbary macaques increasing their range during drier, summer
months. This study highlights how the behavioral plasticity found within the
genus Macaca is reflected in ranging pattern variability within urban
environments.
PMID- 28419551
TI - Two-stage test of means of unordered pairs.
AB - The problem of testing equality of means of a bivariate normal distribution on
the basis of a sample of size n has been considered when the labels of the
observations are either missing or not known. The problem may arise in many
applied settings, especially in genetics. Classical likelihood ratio test fails
here because of identifiability problems. We propose a two-stage testing
procedure using a recently developed test in the context of penalized splines.
The proposed testing procedure is found to outperform the tests proposed in the
literature. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419552
TI - Feasibility and utility of portable ultrasound during retrieval of sick preterm
infants.
AB - AIM: Document the incidence of haemodynamic pathology in critically ill preterm
newborns requiring transport. METHOD: A transport neonatologist performed cardiac
and cerebral ultrasound before and after transportation of infants born <=30
weeks gestation. RESULTS: Forty-four newborns were studied in 2008-2015; of them,
21 were transported by road, 19, by helicopter and four, by fixed wing: median
birthweight, 1130 g (680-1960 g) and median gestation, 27 weeks (23-30); 30 of 44
were male babies. Antenatal steroid course was complete in two babies. Ultrasound
in the referring hospital was at a mean of two hours: 47 minutes (00:15-7:00) of
age. Low systemic blood flow was common: 50% had right ventricular output
<150mL/kg/min and 23%, a superior vena cava flow <50mL/kg/min. at stabilisation.
Cranial US: 10 Grade I IVH, 2 Grade II IVH, 1 Grade IV IVH and 32 normal scans
pretransport. After transport, three further Grade I IVH were reported. Mortality
was higher in the babies with low systemic blood flow: 4 of 12 (33%) died vs 1 of
31 (6%) in the normal flow group (OR = 7.2, 95% CI: 1.1 to 47, p = 0.022).
CONCLUSION: Point-of-care ultrasound during the retrieval of preterm infants
confirms a high incidence of haemodynamic pathology. The use of ultrasound during
transport may provide an opportunity for earlier targeted circulatory support.
PMID- 28419553
TI - Eight-year follow-up after vascularized fibular epiphyseal transfer for hip
reconstruction.
PMID- 28419554
TI - The major miR-31 target genes STK40 and LATS2 and their implications in the
regulation of keratinocyte growth and hair differentiation.
AB - Emerging evidence indicates that even subtle changes in the expression of key
genes of signalling pathways can have profound effects. MicroRNAs (miRNAs) are
masters of subtlety and generally have only mild effects on their target genes.
The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions
associated with activated keratinocytes, such as the hyperproliferative diseases
psoriasis, non-melanoma skin cancer and hair follicle growth. miR-31 is a marker
of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the
function of keratinocytes. This leads to aberrant proliferation, apoptosis, and
differentiation that results in altered hair growth, while the loss of miR-31
leads to increased hair growth. Through in vitro and in vivo studies, we have
defined a set of conserved miR-31 target genes, including LATS2 and STK40, which
serve as new players in the regulation of keratinocyte growth and hair follicle
biology. LATS2 can regulate growth of keratinocytes and we have identified a
function of STK40 that can promote the expression of key hair follicle programme
regulators such as HR, DLX3 and HOXC13.
PMID- 28419555
TI - Antenatal betamethasone for women at risk for late preterm delivery reduces the
rate of neonatal respiratory complications.
PMID- 28419556
TI - Does motor cortex plasticity depend on the type of mutation in the leucine-rich
repeat kinase 2 gene?
PMID- 28419557
TI - Usefulness of the Valsalva maneuver without a mouthpiece to observe the
hypopharynx using transoral endoscopy.
PMID- 28419558
TI - Age but not Philadelphia positivity impairs outcome in older/elderly patients
with acute lymphoblastic leukemia in Sweden.
AB - OBJECTIVES: Older/elderly patients with acute lymphoblastic leukemia (ALL) are
poorly represented in clinical trials. METHODS: Using Swedish national leukemia
registries, we investigated disease/patient characteristics, treatment choices,
outcome, and the impact of an age-adapted protocol (introduced in 2009) in this
population-based study of patients aged 55-85 years, diagnosed with ALL 2005
2012. RESULTS: Of 174 patients, 82% had B-phenotype, 11% Burkitt leukemia
(excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred
in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive
protocols, and 20% with a palliative approach. Higher age and WHO performance
status >=2 influenced the choice of palliation. Intensive, palliative, and both
approaches resulted in complete remission rate 83/16/70% and 3-year overall
survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With
intensive treatment, platelet count <=35*109 /L and age >=75 years were adverse
prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor
in the 55-64 year age-group. CONCLUSIONS: We report a high frequency of Ph+ in
older/elderly patients, with no evidence of poorer outcome compared to Ph
negative disease. Overall prognosis for elderly patients with ALL remains dismal,
despite the use of age-adapted treatment.
PMID- 28419559
TI - Impact of the global burden of periodontal diseases on health, nutrition and
wellbeing of mankind: A call for global action.
AB - BACKGROUND: The global burden of periodontal diseases remains high. Population
growth trends, changes in risk factors and improved tooth retention will increase
the socio-economic burden of periodontitis that is responsible for 3.5 million
years lived with disability, 54 billion USD/year in lost productivity and a major
portion of the 442 billion USD/year cost for oral diseases. METHODS: In the
context of the Milan World Exhibition 2015 "Feeding the Planet, Energy for Life,"
a green paper was developed and offered for global consultation by the European
Federation of Periodontology. The final draft was endorsed by professional
organizations around the world and is presented to stakeholders as a call for
global action. RESULTS: Specific actions for the public, policymakers, educators
and professional organizations have been identified in the areas of prevention,
detection and care. These actions align public interest and knowledge, need for
self-care, professional intervention and policies to the best scientific evidence
to proactively promote periodontal health and effectively manage the global
burden of periodontal diseases, in accordance with WHO/UN priorities and
strategies for tackling common non-communicable diseases via the Common Risk
Factor Approach. CONCLUSIONS: A strong and coherent body of evidence allows
identification of actionable preventive, diagnostic and therapeutic strategies to
effectively promote periodontal health and general wellbeing, and better manage
the socio-economic consequences. Action requires consideration of the specific
national scenarios.
PMID- 28419560
TI - Fibroblast Growth Factor-23 Concentration in Dogs with Chronic Kidney Disease.
AB - BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia,
decreased vitamin D metabolite concentrations, and hyperparathyroidism. This
syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been
shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is
an early biomarker of CKD in people. It is an independent risk factor for both
progression of renal disease and survival time in humans and cats with CKD.
Information about FGF-23 in healthy dogs and those with CKD is lacking.
OBJECTIVES: To measure FGF-23 concentration in dogs with different stages of CKD
and determine its association with factors involved in CKD-MBD, including serum
phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to
validate an ELISA for measurement of plasma FGF-23 concentration in dogs.
ANIMALS: Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy
control dogs. METHODS: Prospective cross-sectional study. An FGF-23 ELISA was
used to measure plasma FGF-23 concentration in dogs and their association with
serum creatinine, phosphorus, calcium, and PTH concentrations. RESULTS: Plasma
FGF-23 concentrations increased with severity of CKD and were significantly
different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001).
Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or
hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations
were the strongest independent predictors of FGF-23 concentration. CONCLUSIONS
AND CLINICAL IMPORTANCE: Plasma FGF-23 concentrations increase in dogs with CKD
as disease progresses. Plasma FGF-23 concentrations appear to be useful for
further study of the pathophysiology of CKD-MBD in dogs.
PMID- 28419561
TI - A transition from using multi-step procedures to a fully integrated system for
performing extracorporeal photopheresis: A comparison of costs and efficiencies.
AB - INTRODUCTION: The Pitie Salpetriere Hospital Hemobiotherapy Department, Paris,
France, has been providing extracorporeal photopheresis (ECP) since November
2011, and started using the Therakos(r) CELLEX(r) fully integrated system in
2012. This report summarizes our single-center experience of transitioning from
the use of multi-step ECP procedures to the fully integrated ECP system,
considering the capacity and cost implications. MATERIALS AND METHODS: The total
number of ECP procedures performed 2011-2015 was derived from department records.
The time taken to complete a single ECP treatment using a multi-step technique
and the fully integrated system at our department was assessed. Resource costs
(2014?) were obtained for materials and calculated for personnel time required.
Time-driven activity-based costing methods were applied to provide a cost
comparison. RESULTS: The number of ECP treatments per year increased from 225
(2012) to 727 (2015). The single multi-step procedure took 270 min compared to
120 min for the fully integrated system. The total calculated per-session cost of
performing ECP using the multi-step procedure was greater than with the CELLEX(r)
system (?1,429.37 and ?1,264.70 per treatment, respectively). CONCLUSIONS: For
hospitals considering a transition from multi-step procedures to fully integrated
methods for ECP where cost may be a barrier, time-driven activity-based costing
should be utilized to gain a more comprehensive understanding the full benefit
that such a transition offers. The example from our department confirmed that
there were not just cost and time savings, but that the time efficiencies gained
with CELLEX(r) allow for more patient treatments per year.
PMID- 28419562
TI - International opinions and national surveillance suggest insufficient consensus
regarding the recognition and management practices of infants with congenital
cytomegalovirus infections.
AB - AIM: This study evaluated the recognition and management practices with regard to
congenital cytomegalovirus (cCMV) infections by a select group of experts and
through a national surveillance study. METHOD: A questionnaire was sent to
international experts involved in mother and infant care in 2014-2015. Monthly
surveillance was conducted among Dutch paediatricians for cases of cCMV
infections from 2013 until 2015. RESULTS: The questionnaire was completed by
63/103 (62%) respondents, who indicated that recognition and management practices
varied. Maternal screening was performed by 17/63 (27%) and infant screening by
3/61 (5%) of the respondents. Infant CMV diagnostics were most frequently
initiated due to hepatosplenomegaly and/or an increase in liver transaminases.
Management practices included cranial ultrasound (57/63, 91%) and audiological
follow-up in symptomatic (61/63, 97%) and asymptomatic (52/63, 83%) infants. In
terms of antiviral treatment, 46/63 (73%) treated symptomatic infants only and
6/63 (9%) treated all infected infants. In total, 48 cases were registered
through the Dutch surveillance study and 43/48 (90%) infants were symptomatic.
CONCLUSION: This study indicates that infants with cCMV infection were
insufficiently recognised and highlights the need for consensus on management
practices. Screening of infants and the development of an international
management guideline are recommended.
PMID- 28419563
TI - Whole exome sequencing identified a novel single base pair insertion mutation in
the EYS gene in a six generation family with retinitis pigmentosa.
AB - Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies
(RD) and is characterized by photoreceptor degeneration. RP is clinically and
genetically heterogeneous disorder. More than 70 genes are known and, thus,
identification of causative genes and mutations in known genes is challenging.
This study was designed to identify the underlying genetic defect in a large
extended Saudi family with multiple RP affected members. Fundus photography,
Optical Coherence Tomography (OCT) and visual field perimetry were performed for
affected individuals. Whole exome sequencing was used to detect the underlying
genetic defect in a large family with 12 affected individuals showing autosomal
recessive isolated RP. WES data analysis identified a novel insertion mutation in
the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger
sequencing validates the variant discovered through exome in all 12 affected
individuals and showed that this mutation is segregating with RP phenotype in an
autosomal recessive manner in 51 individuals of the family tested here. Our study
expands the mutation spectrum of EYS gene in RP patients and extends the body of
evidence that supports the importance of EYS gene in eye development.
PMID- 28419564
TI - Does single mega-dose vitamin A in early neonatal period reduce mortality during
infancy in low- and middle-income countries?
PMID- 28419565
TI - Evolution of silent myocardial ischaemia prevalence and cardiovascular disease
risk factor management in Type 2 diabetes over a 10-year period: an observational
study.
AB - AIMS: To assess the evolution of silent myocardial ischaemia prevalence and of
cardiovascular disease risk factor management over 10 years in people with Type 2
diabetes. METHODS: This repeated cross-sectional study prospectively included 770
people with Type 2 diabetes who presented at our centre in the period 1999-2009.
All had at least one additional cardiovascular disease risk factor, no history of
coronary disease and were screened for silent myocardial ischaemia using
myocardial perfusion imaging. The prevalence of silent myocardial ischaemia,
clinical and biological variables and treatments were collected and compared
among participants screened in three periods: 1999 to 2002; 2003 to 2005; and
2006 to 2009. We also identified predictive factors for silent myocardial
ischaemia. RESULTS: Participants had a mean +/- sd age of 62.3 +/- 9.3 years,
57.4% were men and the mean time from diagnosis of diabetes was 13.4 +/- 9.3
years. Overall, silent myocardial ischaemia screening was positive in 13.9% of
participants. This prevalence decreased sharply over the 10-year study period
(22.6% in 1999-2002, 13.7% in 2003-2005 and 5.9% in 2006-2009; P<0.0001). In
parallel, diastolic and systolic blood pressure, HbA1c and LDL cholesterol
significantly decreased and glitazone and statin use increased (all P<0.001).
Male gender, peripheral artery disease, diastolic blood pressure >80 mmHg and LDL
cholesterol >2.6 mmol/l were independently associated with silent myocardial
ischaemia. Further adjustment showed the screening period had a significant
effect, which erased the effects of diastolic blood pressure and LDL cholesterol.
CONCLUSIONS: The prevalence of silent myocardial ischaemia decreased sharply over
time, and control of the main cardiovascular disease risk factors improved.
Although the causality link cannot be established, the present study supports
current recommendations advocating glycaemic control and intensive management of
cardiovascular factors instead of systematic screening.
PMID- 28419566
TI - Perirhinal accumulation of neuronal alpha-synuclein in a multiple system atrophy
patient with dementia.
AB - We report the case of a 79-year-old Japanese woman who developed cerebellar
ataxia followed by rigidity, dysautonomia and cognitive disorders, and was thus
clinically diagnosed as having possible MSA with dementia. Neuropathological
findings demonstrated not only olivopontocerebellar and striatonigral
degeneration with frequent glial cytoplasmic inclusions (GCIs), but also
degenerative changes in the parahippocampal region, accentuated in the anterior
portion of perirhinal cortex, where neuronal cytoplasmic inclusions (NCIs) and
NFTs were numerous while GCIs were limited. NCIs were frequent in the deep layer,
whereas NFTs were more frequent in superficial cortical layers. Other hippocampal
subregions including subiculum, dentate fascia and cornu ammonis were minimally
involved. NCIs in the perirhinal cortex showed intense argyrophilia with the
Campbell-Switzer silver impregnation method, but not argyrophilic with the
Gallyas method. Most neuronal alpha-synuclein aggregates in dendrosomatic
fraction formed globular/tadpole-like, and ultrastructurally comprised granular
coated fine fibrils 12-24 nm in diameter. To the best of our knowledge, alpha
synuclein-related neuronal pathology localized in the perirhinal region without
hippocampal involvement has not been previously reported in MSA, and may provide
clues to elucidate how neuronal pathology evolves in the
hippocampal/parahippocampal regions in MSA, particularly in cases with dementia.
PMID- 28419568
TI - The influence of noninvasive prenatal testing on gestational age at time of
abortion for aneuploidy.
AB - OBJECTIVE: The objective of this study is to compare the gestational age at
termination for trisomy 13, 18, or 21 (aneuploidy) before and after the
introduction of noninvasive prenatal testing (NIPT). METHODS: A retrospective
cohort of women undergoing termination for aneuploidy at two academic
institutions and one private clinic. We compared two time periods: before and
after the introduction of NIPT (2006-2011 and 2012-2014, respectively). Maternal
demographics and clinical characteristics were abstracted from the medical
record. Nonparametric statistical methods were used to compare the two cohorts.
RESULTS: Our cohort included 93 women: 41 prior to NIPT and 52 post-NIPT.
Maternal age (38 post-NIPT vs 37 pre-NIPT; p = 0.17) did not differ between the
time periods. Women in the post-NIPT were less likely to undergo diagnostic
testing (82.7% vs 97.6%; p < 0.01) before proceeding to abortion after a positive
screening result. In the post-NIPT period, there was a significant decrease in
the gestational age at time of invasive testing (13.0 vs 15.7 weeks; p < 0.01)
and women were more likely to undergo chorionic villous sampling (CVS) (59.6% vs
41.5%; p < 0.01). There was a significant decrease in the gestational age at
termination (14.2 vs 17.2; p < 0.01). Women in the post-NIPT group were less
likely to have terminations after 16 weeks (25.0% vs 61.0%; p < 0.01), 18 weeks
(7.7% vs 39.0%; p < 0.01), or 20 weeks (3.9% vs 12.2%; p = 0.23). CONCLUSION:
With the introduction of NIPT, the median gestational age at diagnosis and
termination for women with Trisomy 13, 18, or 21 was 3 weeks earlier. Women were
four times less likely to have a termination after 18 weeks and three times less
likely to have a termination after 20 weeks. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28419569
TI - Lava lake structure and cloud-like structureless area: new clues for diagnosing
extramammary Paget disease.
PMID- 28419567
TI - Cardiorespiratory physiology in the safe passage study: protocol, methods and
normative values in unexposed infants.
AB - AIM: The Safe Passage Study, conducted by the Prenatal Alcohol in SIDS and
Stillbirth Network, is investigating contributions of prenatal alcohol exposure
to foetal and infant demise. This current report presents physiological data from
full-term infants with no prenatal exposure to alcohol or maternal smoking.
METHODS: Data are from 666 infants from the Northern Plains (North and South
Dakota) and South Africa. A standardised protocol assessed cardiorespiratory
function during baseline and head-up tilts shortly after birth and at one month
of age. RESULTS: Analyses revealed significant increases in heart rate and
decreases in BP from the newborn to one-month time period as well as diminished
heart rate responses to head-up tilt in one-month-old infants. CONCLUSION: The
Safe Passage Study was successful in characterising physiology in a large number
of infants at sites known to have elevated risks for SIDS. Results demonstrate
that even with low prenatal adverse exposures, there are significant changes in
cardiorespiratory function as infants enter the window of increased risk for
SIDS.
PMID- 28419570
TI - Oral lichenoid reactions associated with anti-PD-1/PD-L1 therapies:
clinicopathological findings.
PMID- 28419571
TI - Characterization of mesenchymal stem cells in bovine endometrium during
follicular phase of oestrous cycle.
AB - Stem cells have been postulated as responsible for cell regeneration in highly
and continuously regenerative tissues such as the endometrium. Few studies in
cattle have identified and specified the presence of stem cells in the
endometrium during the oestrous cycle. The aim of this study was to investigate
the presence of mesenchymal stem cells (MSCs) in the bovine endometrium during
the follicular phase (FP) of the oestrous cycle. Uterine tissue was collected in
the time-frame comprising day 18 of the cycle and ovulation (day 0). We isolated,
cultured and expanded four primary cell lines from endometrium and identified
byRT-qPCR the expression of OCT4, SOX2 but not NANOG (undifferentiated/embryonic
markers), CD44 (MSCs marker) and c-KIT (stem cell marker) genes; and the encoded
Oct4, Sox2 and Cd44 proteins by Western blot or immunostaining of paraffin
embedded tissue in endometrium. We demonstrated that cells isolated from bovine
endometrium displayed essentially the same gene expression pattern; however, at
the protein level, Oct4 and Cd44 were not detected. Besides, they showed typical
functional characteristics of MSCs such as fibroblast-like morphology, plastic
adherence, high proliferative capacity, clone formation in vitro and the ability
to differentiate into chondrogenic, osteogenic and adipogenic lineages. We
obtained for the first time an extensive characterization of undifferentiated
cells populations contained in the bovine endometrium during the FP of the
oestrous cycle.
PMID- 28419572
TI - Genomewide differential expression profiling of long non-coding RNAs in
androgenetic alopecia in a Chinese male population.
AB - BACKGROUND: Androgenetic alopecia (AGA), or male pattern baldness (MPB), is the
most common form of hair loss in males. A combination of genetic and androgen
causes have been suggested as factors that contribute to the development of AGA.
However, the specific molecular mechanisms that underly AGA remain largely
unknown. Long non-coding RNAs (lncRNAs), a new class of regulatory non-coding
RNAs that are longer than 200 nucleotides, have been shown to play important
roles in a number of cellular processes, including transcription, chromosome
remodelling and post-transcriptional processing. The dysregulation of lncRNAs is
associated with many forms of diseases, but it remains unknown whether lncRNAs
are associated with AGA. OBJECTIVE: The aim of this study was to identify AGA
associated lncRNAs and predict the potential roles of these lncRNAs in AGA.
METHODS: A genomewide microarray was used to identify lncRNAs that are
differentially expressed between AGA and adjacent normal tissues. Real-time qRT
PCR was used to validate the microarray data. RESULTS: A large number of lncRNAs
were differentially expressed (fold change >2.4) between AGA and adjacent normal
tissues. Of these, 770 were upregulated and 1373 were downregulated. Moreover,
pathway analysis revealed that 53 functional pathways were associated with the
upregulated transcripts, while 11 pathways were associated with the downregulated
transcripts. CONCLUSION: To our knowledge, this is the first study to investigate
AGA-associated lncRNAs. lncRNA profiles are altered in AGA, and these lncRNAs and
their target genes may serve as novel candidates for preventing and treating AGA.
PMID- 28419573
TI - Impella 2.5 initiated prior to unprotected left main PCI in acute myocardial
infarction complicated by cardiogenic shock improves early survival.
AB - OBJECTIVES: To assess post-procedural outcomes when Impella 2.5 percutaneous left
ventricular assist device (pLVAD) support is initiated either prior to or after
percutaneous coronary intervention (PCI) on unprotected left main coronary artery
(ULMCA) culprit lesion in the context of acute myocardial infarction cardiogenic
shock (AMICS). BACKGROUND: Initiation of Impella 2.5 pLVAD prior to PCI is
associated with significant survival benefit in the setting of AMICS. Outcomes of
those presenting with a ULMCA culprit lesion in this setting have not been well
characterized. METHODS: Thirty-six consecutive patients in the cVAD Registry
supported with Impella 2.5 pLVAD for AMICS who underwent PCI on ULMCA culprit
lesion were included in our multicenter study. RESULTS: The average age was 69.8
+/- 14.2 years, 77.8% were male, 72.7% were in CS at admission, 44.4% sustained
one or multiple cardiac arrests, and 30.6% had anoxic brain injury. Baseline
characteristics were comparable between the Pre-PCI group (n = 20) and Post-PCI
group (n = 16). Non-ST segment elevation myocardial infarction and greater
coronary disease burden were significantly more frequent in the Pre-PCI group but
they had significantly better survival to discharge (55.0% vs 18.8%, P = 0.041).
Kaplan-Meier 30-day survival analysis showed very poor survival in Post-PCI group
(48.1% vs 12.5%, Log-Rank P = 0.004). CONCLUSIONS: Initiation of Impella 2.5
pLVAD prior to as compared with after PCI of ULMCA for AMICS culprit lesion is
associated with significant early survival. As previously described, patients
supported after PCI appear to have very poor survival at 30 days.
PMID- 28419574
TI - Phototherapy and photochemotherapy for polymorphic light eruption
desensitization: a five-year case series review from a university teaching
hospital.
PMID- 28419575
TI - Prepubertal vulvar fibroma, a rare entity little known to dermatologists: report
of two cases.
PMID- 28419576
TI - Agreement between rapid on-site evaluation and the final cytological diagnosis of
salivary gland specimens.
AB - OBJECTIVE: Rapid on-site evaluation (ROSE) has been shown to be beneficial in
determining the adequacy and a preliminary diagnosis in multiple organ systems.
However, little is known regarding the diagnostic values and agreement of ROSE
compared with a final cytological diagnosis in salivary gland fine needle
aspiration (FNA). The aim of the present study was to evaluate agreement and
compare accuracy between ROSE and a final cytological diagnosis of salivary gland
FNA, using a final histological diagnosis as a gold standard. METHODS: All
patients with salivary gland lesions who underwent FNA with ROSE during 2009 to
2013 were evaluated. The patient demographic data, clinical characteristics,
ROSE, final cytological diagnosis and final histological diagnosis were obtained.
Agreement and accuracy were assessed by Kappa statistic and receiver-operating
characteristic (ROC) curve analysis, respectively. RESULTS: Of 386 FNAs with
ROSE, 248 (64%) lesions were from parotid glands, and 171 (44%) had histological
follow-up results. Agreement between ROSE and the final cytological diagnosis was
good to excellent (simple kappa = 0.76; linear weighted kappa = 0.81). There were
discrepancies in 25 lesions (6.8%). Of these, 10 (2.7%) were major discrepancies,
resulting in a change in clinical management. Only one of 36 malignant lesions by
ROSE was downgraded to suspicious. No significant difference was found in
accuracy between two interpretations (area under the curve 0.82 vs 0.84, P=.17).
CONCLUSION: These findings suggest that, in addition to an excellent agreement
and comparably good accuracy between ROSE and final cytological evaluation,
malignant results of ROSE may be useful to facilitate an early clinical decision.
PMID- 28419577
TI - Decline in new psychoactive substance use disorders following legislation
targeting headshops: Evidence from national addiction treatment data.
AB - INTRODUCTION AND AIMS: New psychoactive substances (NPS) have hedonic effects
that may lead to dependence. Headshops selling NPS increased in number in Ireland
from late 2009. Legislation was enacted in May and August of 2010 that caused
their closure. It is unknown whether such events impact the rate of NPS use
disorders. DESIGNS AND METHODS: We conducted a population-based study using the
Irish national database of episodes of addiction treatment between 2009 and 2012.
We examined trends in the rate of NPS-related treatment episodes among young
adults. Joinpoint trend analysis software was used to identify significant
changes in trend. RESULTS: Of the 31 284 episodes of addiction treatment
commenced by adults aged 18 to 34 years, 756 (2.4%) were NPS related. In 2012,
the 12-month moving average rate had fallen 48% from its peak in 2010, from
9.0/100 000 to 4.7/100 000. Joinpoint analysis indicated that the rate of NPS
related episodes increased by 218% (95% confidence interval 86 to 445, P = 0.001)
every 4 months until the first third of 2010. From that point, the rate declined
by 9.8% (95% confidence interval -14.1 to -5.4, P = 0.001) per 4-month period.
There was no significant trend change in the rate of non-NPS related treatment
episodes. DISCUSSION AND CONCLUSIONS: Over the 2 years after the enactment of
prohibition-styled legislation targeting NPS and headshops, the rate of NPS
related addiction treatment episodes among young adults declined progressively
and substantially. We found no coinciding trend change in the rate of episodes
linked to other drug groups. [Smyth BP, Lyons S, Cullen W. Decline in new
psychoactive substance use disorders following legislation targeting headshops:
Evidence fromnational addiction treatment data. Drug Alcohol Rev 2017;00:000
000].
PMID- 28419578
TI - Disordered eating patterns in coeliac disease: a framework analysis.
AB - OBJECTIVE: The need for dietary-management in coeliac disease may lead to the
development of disordered eating patterns. A theoretical model of disordered
eating has been proposed to explain disordered eating in coeliac disease. The aim
of this study was to explore the experiences of typical and disordered eating in
coeliac disease to gain a greater understanding of these processes and explore
specific pathways within this model. METHODS: We interviewed 21 individuals with
coeliac disease, recruited from a previous database, about their experiences with
food and food environments. Information about disordered eating status was
assessed via questionnaire. The interviews were analysed qualitatively using
Framework analysis, which was underpinned by the theoretical model of disordered
eating in coeliac disease. RESULTS: Experiences differed between participants
scoring high on measures of disordered eating and those who scored low (typical
eaters). Participants scoring high on measures of disordered eating were
concerned about the consequences of their gluten-free diet on body image and they
described eating patterns similar to binge/restrict cycles. Typical eaters
reported being able to integrate their dietary self-management into their daily
lives; however, general concerns around food and cross-contamination were
associated with a restriction in food intake. CONCLUSIONS: Coeliac disease has a
varied impact on eating patterns. The need to follow a gluten-free diet and to be
vigilant around food has to be balanced with concerns around food availability
and cross-contamination which have the potential to contribute towards disordered
eating attitudes and behaviours. The findings suggest that the theoretical model
of disordered eating provides an adequate explanation of disordered eating
patterns in coeliac disease.
PMID- 28419581
TI - Successful kidney transplantation in highly sensitized, ultra-long-term dialysis
patients.
PMID- 28419579
TI - Erdj3 Has an Essential Role for Z Variant Alpha-1-Antitrypsin Degradation.
AB - Alpha-1-antitrypsin deficiency (AATD) is an inherited disease characterized by
emphysema and liver disease. AATD is most often caused by a single amino acid
substitution at amino acid 342 in the mature protein, resulting in the Z mutation
of the alpha-1-antitrypsin gene (ZAAT). This substitution is associated with
misfolding and accumulation of ZAAT in the endoplasmic reticulum (ER) of
hepatocytes and monocytes, causing a toxic gain of function. Retained ZAAT is
eliminated by ER-associated degradation and autophagy. We hypothesized that alpha
1-antitrypsin (AAT)-interacting proteins play critical roles in quality control
of human AAT. Using co-immunoprecipitation, we identified ERdj3, an ER-resident
Hsp40 family member, as a part of the AAT trafficking network. Depleting ERdj3
increased the rate of ZAAT degradation in hepatocytes by redirecting ZAAT to the
ER calreticulin-EDEM1 pathway, followed by autophagosome formation. In the Huh7.5
cell line, ZAAT ER clearance resulted from enhancing ERdj3-mediated ZAAT
degradation by silencing ERdj3 while simultaneously enhancing autophagy. In this
context, ERdj3 suppression may eliminate the toxic gain of function associated
with polymerization of ZAAT, thus providing a potential new therapeutic approach
to the treatment of AATD-related liver disease. J. Cell. Biochem. 118: 3090-3101,
2017. (c) 2017 The Authors. Journal of Cellular Biochemistry Published by Wiley
Periodicals Inc.
PMID- 28419580
TI - Liquid/Liquid Interfacial Synthesis of a Click Nanosheet.
AB - A liquid/liquid interfacial synthesis is employed, for the first time, to
synthesize a covalent two-dimensional polymer nanosheet. Copper-catalyzed azide
alkyne cycloaddition (CuAAC) between a three-way terminal alkyne and azide at a
water/dichloromethane interface generates a 1,2,3-triazole-linked nanosheet. The
resultant nanosheet, with a flat and smooth texture, has a maximum domain size of
20 MUm and minimum thickness of 5.3 nm. The starting monomers in the organic
phase and the copper catalyst in the aqueous phase can only meet at the
liquid/liquid interface as a two-dimensional reaction space; this allows them to
form the two-dimensional polymer. The robust triazole linkage generated by
irreversible covalent-bond formation allows the nanosheet to resist hydrolysis
under both acidic and alkaline conditions, and to endure pyrolysis up to more
than 300 degrees C. The coordination ability of the triazolyl group enables the
nanosheet to act as a reservoir for metal ions, with an affinity order of Pd2+
>Au3+ >Cu2+ .
PMID- 28419582
TI - Free-breathing liver fat quantification using a multiecho 3D stack-of-radial
technique.
AB - PURPOSE: The diagnostic gold standard for nonalcoholic fatty liver disease is an
invasive biopsy. Noninvasive Cartesian MRI fat quantification remains limited to
a breath-hold (BH). In this work, a novel free-breathing 3D stack-of-radial (FB
radial) liver fat quantification technique is developed and evaluated in a
preliminary study. METHODS: Phantoms and healthy subjects (n = 11) were imaged at
3 Tesla. The proton-density fat fraction (PDFF) determined using FB radial (with
and without scan acceleration) was compared to BH single-voxel MR spectroscopy
(SVS) and BH 3D Cartesian MRI using linear regression (correlation coefficient
rho and concordance coefficient rhoc ) and Bland-Altman analysis. RESULTS: In
phantoms, PDFF showed significant correlation (rho > 0.998, rhoc > 0.995) and
absolute mean differences < 2.2% between FB radial and BH SVS, as well as
significant correlation (rho > 0.999, rhoc > 0.998) and absolute mean
differences < 0.6% between FB radial and BH Cartesian. In the liver and abdomen,
PDFF showed significant correlation (rho > 0.986, rhoc > 0.985) and absolute
mean differences < 1% between FB radial and BH SVS, as well as significant
correlation (rho > 0.996, rhoc > 0.995) and absolute mean differences < 0.9%
between FB radial and BH Cartesian. CONCLUSION: Accurate 3D liver fat
quantification can be performed in 1 to 2 min using a novel FB radial technique.
Magn Reson Med 79:370-382, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28419583
TI - Comparison of multifactor scoring systems and single serum markers for the early
prediction of the severity of acute pancreatitis.
AB - BACKGROUND: The purpose of this study was to clarify whether the current scoring
systems and single serum markers used in pancreatitis remain applicable for the
early prediction of infected pancreatic necrosis (IPN) and the severity and
mortality of acute pancreatitis (AP) in accordance with the revised Atlanta and
determinant-based classifications. METHODS: Demographic, clinical, and laboratory
data from 708 consecutive patients with AP were prospectively collected between
January 2011 and December 2012. The severity was classified using the revised
Atlanta and determinant-based classification systems. The predictive accuracies
for moderately severe AP (MSAP), severe AP (SAP), critically severe AP (CAP),
IPN, and mortality were measured using area under the receiver operating
characteristic curves. RESULTS: The receiver operating characteristic analysis
showed that the multifactor scoring systems and single serum markers had a low
predictive accuracy regarding moderately severe AP. The Acute Physiology and
Chronic Health Evaluation (APACHE) II score had the highest accuracy in
predicting SAP with area under the curve (AUC) values of 0.75 (95% CI = 0.71
0.79) and 0.77 (95% CI = 0.73-0.81) at 24 and 48 h after admission, respectively.
Procalcitonin was the most accurate predictor for CAP and IPN, with respective
AUCs of 0.86 (95% CI = 0.82-0.89) and 0.83 (95% CI = 0.78-0.87) at 48 h after
admission. In predicting mortality, both the APACHE II score and blood urea
nitrogen had the highest accuracy. CONCLUSIONS: The APACHE II score had the
highest predictive accuracy for SAP and mortality as defined by the revised
Atlanta classification, whereas procalcitonin was the most accurate predictor for
CAP and IPN.
PMID- 28419584
TI - Context-dependent function of ROS in the vascular endothelium: The role of the
Notch pathway and shear stress.
AB - Reactive oxygen species (ROS) act as signal molecules in several biological
processes whereas excessive, unregulated, ROS production contributes to the
development of pathological conditions including endothelial dysfunction and
atherosclerosis. The maintenance of a healthy endothelium depends on many factors
and on their reciprocal interactions; in this framework, the Notch pathway and
shear stress (SS) play two lead roles. Recently, evidence of a crosstalk between
ROS, Notch, and SS, is emerging. The aim of this review is to describe the way
ROS interact with the Notch pathway and SS protecting from-or promoting-the
development of endothelial dysfunction. (c) 2017 BioFactors, 43(4):475-485, 2017.
PMID- 28419585
TI - A new discrepancy of HPA-3 genotyping because of a rare HPA-27bw polymorphism.
PMID- 28419586
TI - A review of the nutritional challenges experienced by people living with severe
mental illness: a role for dietitians in addressing physical health gaps.
AB - People experiencing a severe mental illness (SMI), such as schizophrenia,
schizoaffective disorder, bipolar affective disorder or depression with psychotic
features, have a 20-year mortality gap compared to the general population. This
'scandal of premature mortality' is primarily driven by preventable
cardiometabolic disease, and recent research suggests that the mortality gap is
widening. Multidisciplinary mental health teams often include psychiatrists,
clinical psychologists, specialist mental health nurses, social workers and
occupational therapists, offering a range of pharmacological and
nonpharmacological treatments to enhance the recovery of clients who have
experienced, or are experiencing a SMI. Until recently, lifestyle and life skills
interventions targeting the poor physical health experienced by people living
with SMI have not been offered in most routine clinical settings. Furthermore,
there are calls to include dietary intervention as mainstream in psychiatry to
enhance mental health recovery. With the integration of dietitians being a
relatively new approach, it is important to review and assess the literature to
inform practice. This review assesses the dietary challenges experienced by
people with a SMI and discusses potential strategies for improving mental and
physical health.
PMID- 28419587
TI - An oligogalacturonide-derived molecular probe demonstrates the dynamics of
calcium-mediated pectin complexation in cell walls of tip-growing structures.
AB - Pectic homogalacturonan (HG) is one of the main constituents of plant cell walls.
When processed to low degrees of esterification, HG can form complexes with
divalent calcium ions. These macromolecular structures (also called egg boxes)
play an important role in determining the biomechanics of cell walls and in
mediating cell-to-cell adhesion. Current immunological methods enable only steady
state detection of egg box formation in situ. Here we present a tool for
efficient real-time visualisation of available sites for HG crosslinking within
cell wall microdomains. Our approach is based on calcium-mediated binding of
fluorescently tagged long oligogalacturonides (OGs) with endogenous de-esterified
HG. We established that more than seven galacturonic acid residues in the HG
chain are required to form a stable complex with endogenous HG through calcium
complexation in situ, confirming a recently suggested thermodynamic model. Using
defined carbohydrate microarrays, we show that the long OG probe binds
exclusively to HG that has a very low degree of esterification and in the
presence of divalent ions. We used this probe to study real-time dynamics of HG
during elongation of Arabidopsis pollen tubes and root hairs. Our results suggest
a different spatial organisation of incorporation and processing of HG in the
cell walls of these two tip-growing structures.
PMID- 28419588
TI - Endoscopic treatment of intraductal pancreatic stent fragmentation.
AB - BACKGROUND AND AIM: Complications of endoscopic treatment are reported more and
more often as a result of popularization of pancreatic endotherapy. Our study
presents the results of treatment in patients with intraductal pancreatic stent
fragmentation diagnosed during endotherapy of chronic pancreatitis. METHODS:
Retrospective analysis of 2496 endoscopic retrograde cholangiopancreatography
procedures which were carried out in 607 patients at the Gastrointestinal
Endoscopy Unit of the University Clinical Center in Gdansk. RESULTS: In the
course of pancreatic endotherapy, intraductal pancreatic stent fragmentation was
stated during 33 of 2496 (0.013%) procedures in 33 of 607 (5.44%) patients with
chronic pancreatitis. In 33 patients, there were 46 intraductal fragments of
broken stents. Most patients were asymptomatic. In 31/33 patients, fragments of
broken stents were removed from the pancreatic duct endoscopically. In the case
of two patients, endoscopic management was ineffective and they were treated
surgically. Altogether, 44/46 stent fragments were removed endoscopically. Most
fragments of pancreatic stents were removed during the first endoscopic
procedure. One fragment of a broken stent was retrieved with polypectomy snare
and four with Dormia basket. The remaining fragments of broken pancreatic stents
were removed with rat-tooth forceps. CONCLUSIONS: Intraductal fragmentation of
pancreatic stent is a rare complication of pancreatic endotherapy and it often
has an asymptomatic course. Most fragments of broken pancreatic stents can be
removed endoscopically from the pancreatic duct with an acceptable complication
rate.
PMID- 28419589
TI - Child health in Sweden is characterised by good health and low accidents, but
rising psychological problems.
PMID- 28419590
TI - Cracking the neural code, treating paralysis and the future of bioelectronic
medicine.
AB - The human nervous system is a vast network carrying not only sensory and movement
information, but also information to and from our organs, intimately linking it
to our overall health. Scientists and engineers have been working for decades to
tap into this network and 'crack the neural code' by decoding neural signals and
learning how to 'speak' the language of the nervous system. Progress has been
made in developing neural decoding methods to decipher brain activity and
bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and
for diagnosing brain-related diseases such as Parkinson's and Alzheimer's
disease. In a recent first-in-human study involving paralysis, a paralysed male
study participant regained movement in his hand, years after his injury, through
the use of a bioelectronic neural bypass. This work combined neural decoding and
neurostimulation methods to translate and re-route signals around damaged neural
pathways within the central nervous system. By extending these methods to
decipher neural messages in the peripheral nervous system, status information
from our bodily functions and specific organs could be gained. This, one day,
could allow real-time diagnostics to be performed to give us a deeper insight
into a patient's condition, or potentially even predict disease or allow early
diagnosis. The future of bioelectronic medicine is extremely bright and is wide
open as new diagnostic and treatment options are developed for patients around
the world.
PMID- 28419591
TI - Application of spin echoes in the regime of weak dephasing to T1 -mapping of the
lung.
AB - PURPOSE: This work presents an approach to mapping the entire lung's proton
density and T1 within a single breath-hold and analyzes the apparent T1 when
exciting with a spin echo generating pulse in comparison to a standard gradient
echo acquisition. METHODS: An inversion-recovery SNAPSHOT-FLASH sequence with a
stack-of-stars k-space readout with a golden angle increment was modified to use
a spin echo generating radiofrequency-pulse for excitation. Data of five
volunteers were acquired on a 3T scanner and image reconstruction was performed
by an iterative algorithm adopted from MR-Fingerprinting. RESULTS: The
feasibility of acquiring quantitative maps of the entire lung with a resolution
of 5 * 5 * 10 mm within 7.5 s is demonstrated. It is shown that the proposed spin
echo forming radiofrequency-pulse increases the apparent proton density compared
to a rectangular pulse. Further, the apparent T1 is reduced in the spin echo case
compared to the gradient echo sequence. CONCLUSION: The proposed spin echo based
method results in T1 maps that are comparable to the ones that were acquired with
ultra-short echo time sequences elsewhere. The T1 shortening is believed to
originate from increased signal contributions of the extra vascular compartment,
which has a short T2* and T1 . Magn Reson Med 79:960-967, 2018. (c) 2017
International Society for Magnetic Resonance in Medicine.
PMID- 28419592
TI - Catalyst Optimisation for Asymmetric Synthesis by Ligand Chirality Element
Addition: A Perspective on Stereochemical Cooperativity.
AB - The concept of matched and mismatched stereochemical pairings has been utilised
extensively in organic synthesis, with the cooperativity resulting from the
former enabling many reactions to proceed with high stereoselectivity. This
approach was first developed to improve the diastereoselectivity of a reaction by
matching the configuration of an enantiopure reagent or catalyst with the
configuration of an enantiopure substrate. It has been extended to the asymmetric
transformation of prochiral substrates controlled by reagents and catalysts
containing two or more stereogenic centres. Matched and mismatched pairings may
again be identified, with the former resulting in higher product
enantioselectivity. This Minireview examines stereochemical pairings within
catalysts generated from the combination of a metal with an enantiopure ligand;
specifically examples in which the ligand diastereoisomers examined for
cooperativity are formally the result of the addition of a chiral element to an
existing enantiopure ligand. Comparison of all three ligands in each of the fifty
six examples examined reveals that, in the majority of cases, the added element
of chirality increases and decreases the enantioselectivity with respect to the
parent ligand. The iterative application of this effect offers a potentially
powerful method for catalyst optimisation for use in asymmetric synthesis.
PMID- 28419594
TI - Catheter ablation for the treatment of atrial fibrillation is associated with a
reduction in health care resource utilization.
AB - BACKGROUND: Catheter ablation (CA) is superior to antiarrhythmic therapy at
reducing recurrence of atrial fibrillation (AF); however, there are limited data
regarding whether this decrease translates into a reduction in health care
resource utilization. OBJECTIVE: To evaluate the impact of AF ablation on long
term health care resource utilization. METHODS: A population-based cohort was
constructed to include patients who underwent CA for AF in Quebec, Canada,
between April 2005 and March 2011. Resource utilization was evaluated 24 months
pre- and postindex CA procedure. RESULTS: In a cohort of 1,556 patients, resource
utilization increased progressively over the 24-month period leading to index CA
(P for trend <0.05 for hospitalizations, ER visits, outpatient visits,
cardioversions, and echocardiograms). After index CA, all-cause hospitalizations,
hospitalizations for AF, ER visits, cardioversions, and echocardiograms were
reduced 12 months post-CA compared to 12 months prior (all-cause hospitalizations
0.8-0.6 per patient per year; hospitalizations for AF 0.4-0.3; ER visits 2.9-1.8;
cardioversions 0.5-0.2; echocardiograms 0.8-0.5; P < 0.05 for all trends).
Resource utilization continued to decline at 24 months post-CA (vs. 12 months
prior) for all-cause hospitalizations (0.4), cardioversions (0.1), and
echocardiograms (0.3) (per patient year; P < 0.05 for all trends). CONCLUSION: In
conclusion, the pattern of increasing health care resource utilization preceding
CA for AF reverses after CA to lower than preablation levels up to 24 months post
CA.
PMID- 28419593
TI - Protein sumoylation and phosphorylation intersect in Arabidopsis signaling.
AB - Conjugation of the small ubiquitin-related modifier (SUMO) to protein substrates
has an impact on stress responses and on development. We analyzed the proteome
and phosphoproteome of mutants in this pathway. The mutants chosen had defects in
SUMO ligase SIZ1, which catalyzes attachment of single SUMO moieties onto
substrates, and in ligases PIAL1 and PIAL2, which are known to form SUMO chains.
A total of 2657 proteins and 550 phosphopeptides were identified and quantified.
Approximately 40% of the proteins and 20% of the phosphopeptides showed
differences in abundance in at least one of the analyzed genotypes, demonstrating
the influence of SUMO conjugation on protein abundance and phosphorylation. The
data show that PIAL1 and PIAL2 are integral parts of the SUMO conjugation system
with an impact on stress response, and confirm the involvement of SIZ1 in plant
defense. We find a high abundance of predicted SUMO attachment sites in
phosphoproteins (70% versus 40% in the total proteome), suggesting convergence of
phosphorylation and sumoylation signals onto a set of common targets.
PMID- 28419596
TI - Effects of culture conditions on the size, morphology and wet density of spores
of Bacillus cereus 569 and Bacillus megaterium QM B1551.
AB - : The influence of variable culture conditions on the size and wet density of
spores of Bacillus cereus and Bacillus megaterium were examined in this work.
Culture temperature and initial pH was shown to have a significant impact on the
size of both species, with increasingly alkaline culture media and elevated
culture temperatures resulting in spores that were, on average, up to 25% reduced
in volume. Increasing concentrations of inorganic salts in sporulation media
exerted differing effects on each species; whereas a fivefold increase in the
concentration of all salts resulted in only minor differences to the dimensions
of B. cereus spores, B. megaterium spores became more elongated, displaying an
average increase in volume of almost 30%. Similarly, as the spore elongated to
yield aspect ratios larger than 1.4, their shape changed from typical prolate
spheroids to cylinders with hemispherical ends. In contrast with previous
studies, culture conditions employed in this study exerted no discernible impact
on the wet density of B. cereus or B. megaterium spores. SIGNIFICANCE AND IMPACT
OF THE STUDY: Bacterial spores of the genera Bacillus and Clostridium represent
nature's most durable cells in terms of their extreme resistance to a variety of
deleterious environments. As a result, they are of concern in the food
processing, healthcare and other sectors, and are of increasing biotechnological
interest. Improved understanding of variance in spore size, morphology and
density may aid the development of certain spore-associated applications (e.g.
spore surface display) while contributing to active areas of research such as
spore adhesion and resistance to heat.
PMID- 28419595
TI - Lipopolysaccharide binding to the periplasmic protein LptA.
AB - Lipopolysaccharide (LPS) and the periplasmic protein, LptA, are two essential
components of Gram-negative bacteria. LPS, also known as endotoxin, is found
asymmetrically distributed in the outer leaflet of the outer membrane of Gram
negative bacteria such as Escherichia coli and plays a role in the organism's
natural defense in adverse environmental conditions. LptA is a member of the
lipopolysaccharide transport protein (Lpt) family, which also includes LptC,
LptDE, and LptBFG2 , that functions to transport LPS through the periplasm to the
outer leaflet of the outer membrane after MsbA flips LPS across the inner
membrane. It is hypothesized that LPS binds to LptA to cross the periplasm and
that the acyl chains of LPS bind to the central pocket of LptA. The studies
described here are the first to comprehensively characterize and quantitate the
binding of LPS by LptA. Using site-directed spin-labeling electron paramagnetic
resonance (EPR) spectroscopy, data were collected for 15 spin-labeled residues in
and around the proposed LPS binding pocket on LptA to observe the mobility
changes caused by the presence of exogenous LPS and identify the binding location
of LPS to LptA. The EPR data obtained suggest a 1:1 ratio for the LPS:LptA
complex and allow the first calculation of dissociation constants for the LptA
LPS interaction. The results indicate that the entire protein is affected by LPS
binding, the N-terminus unfolds in the presence of LPS, and a mutant LptA protein
unable to form oligomers has an altered affinity for LPS.
PMID- 28419597
TI - Growth rate correlates negatively with protein turnover in Arabidopsis
accessions.
AB - Previous studies with Arabidopsis accessions revealed that biomass correlates
negatively to dusk starch content and total protein, and positively to the
maximum activities of enzymes in photosynthesis. We hypothesized that large
accessions have lower ribosome abundance and lower rates of protein synthesis,
and that this is compensated by lower rates of protein degradation. This would
increase growth efficiency and allow more investment in photosynthetic machinery.
We analysed ribosome abundance and polysome loading in 19 accessions, modelled
the rates of protein synthesis and compared them with the observed rate of
growth. Large accessions contained less ribosomes than small accessions, due
mainly to cytosolic ribosome abundance falling at night in large accessions. The
modelled rates of protein synthesis resembled those required for growth in large
accessions, but were up to 30% in excess in small accessions. We then employed 13
CO2 pulse-chase labelling to measure the rates of protein synthesis and
degradation in 13 accessions. Small accessions had a slightly higher rate of
protein synthesis and much higher rates of protein degradation than large
accessions. Protein turnover was negligible in large accessions but equivalent to
up to 30% of synthesised protein day-1 in small accessions. We discuss to what
extent the decrease in growth in small accessions can be quantitatively explained
by known costs of protein turnover and what factors may lead to the altered
diurnal dynamics and increase of ribosome abundance in small accessions, and
propose that there is a trade-off between protein turnover and maximisation of
growth rate.
PMID- 28419598
TI - Biological traits, rather than environment, shape detection curves of large
vertebrates in neotropical rainforests.
AB - Line transect surveys are widely used in Neotropical rainforests to estimate the
population abundance of medium- and large-sized vertebrates. The use of indices
such as encounter rate has been criticized because the probability of animal
detection may fluctuate due to the heterogeneity of environmental conditions
among sites. In addition, the morphological and behavioral characteristics
(biological traits) of species affect their detectability. In this study, we
compared the extent to which environmental conditions and species' biological
traits bias abundance estimates in terra firme rainforests in French Guiana. The
selected environmental conditions included both physical conditions and forest
structure covariates, while the selected biological traits included the
morphological and behavioral characteristics of species. We used the distance
sampling method to model the detection probability as an explicit function of
environmental conditions and biological traits and implemented a model selection
process to determine the relative importance of each group of covariates.
Biological traits contributed to the variability of animal detectability more
than environmental conditions, which had only a marginal effect. Detectability
was best for large animals with uniform or disruptive markings that live in
groups in the canopy top. Detectability was worst for small, solitary,
terrestrial animals with mottled markings. In the terra firme rainforests that
represent ~80% of the Amazonia and Guianas regions, our findings support the use
of relative indices such as the encounter rate to compare population abundance
between sites in species-specific studies. Even though terra firme rainforests
may appear similar between regions of Amazonia and the Guianas, comparability
must be ensured, especially in forests disturbed by human activity. The detection
probability can be used as an indicator of species' vulnerability to hunting and,
thus, to the risk of local extinction. Only a few biological trait covariates are
required to correctly estimate the detectability of the majority of medium- and
large-sized vertebrates. Thus, a biological trait model could be useful in
predicting the detection probabilities of rare, uncommon, or localized species
for which few data are available to fit the detection function.
PMID- 28419600
TI - Reformulations of well-known active ingredients in the topical treatment of
psoriasis vulgaris can improve clinical outcomes for patients.
AB - Although the majority of patients with psoriasis vulgaris are treated exclusively
with topical therapies, research to develop more effective topical therapies that
are associated with higher patient satisfaction has lagged behind the development
of systemic agents. The aim of this literature review was to determine whether
there is documented evidence that applying an innovative approach to improving
the formulation of active ingredients commonly used in the topical treatment of
psoriasis can have a positive effect on clinical outcomes and patient-reported
outcomes (PROs). The Embase and PubMed databases were searched for articles
published between 2001 and 2016 that made direct head-to-head comparisons of
different formulations of an active pharmaceutical ingredient (API), focusing on
clinical outcomes and PROs. In total, 22 publications on APIs or API combinations
met the eligibility criteria (19 head-to-head clinical trials, one pooled
analysis, one health-economic modelling study and one systematic review).
Significant clinical benefit associated with the use of a reformulated API over
an older formulation was reported in three trials of clobetasol propionate, one
trial of calcipotriol, three trials of betamethasone and five trials/pooled
analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD)
formulations. Significantly improved PROs associated with the use of a
reformulated API over an older formulation were reported in three trials of
clobetasol propionate, one trial of betamethasone valerate and two trials of
Cal/BD formulations. These results demonstrate that the innovative reformulation
of APIs used in the treatment of psoriasis can produce therapies that attain
significantly improved clinical outcomes and PROs. This suggests that improvement
in topical therapy for psoriasis need not only to be achieved by the
identification of new targets and the development of new APIs, but that
improvement in the vehicle used to deliver existing APIs has the potential to
result in significant clinical and patient benefits.
PMID- 28419601
TI - Is high-flow nasal cannula noninferior to nasal CPAP for the initial management
of preterm infants?
PMID- 28419599
TI - Mycobacterium tuberculosis proteasomal ATPase Mpa has a beta-grasp domain that
hinders docking with the proteasome core protease.
AB - Mycobacterium tuberculosis (Mtb) has a proteasome system that is essential for
its ability to cause lethal infections in mice. A key component of the system is
the proteasomal adenosine triphosphatase (ATPase) Mpa, which captures, unfolds,
and translocates protein substrates into the Mtb proteasome core particle for
degradation. Here, we report the crystal structures of near full-length hexameric
Mtb Mpa in apo and ADP-bound forms. Surprisingly, the structures revealed a
ubiquitin-like beta-grasp domain that precedes the proteasome-activating carboxyl
terminus. This domain, which was only found in bacterial proteasomal ATPases,
buries the carboxyl terminus of each protomer in the central channel of the
hexamer and hinders the interaction of Mpa with the proteasome core protease.
Thus, our work reveals the structure of a bacterial proteasomal ATPase in the
hexameric form, and the structure finally explains why Mpa is unable to stimulate
robust protein degradation in vitro in the absence of other, yet-to-be-identified
co-factors.
PMID- 28419602
TI - Physics for clinicians: Fluid-attenuated inversion recovery (FLAIR) and double
inversion recovery (DIR) Imaging.
AB - : A pedagogical review of fluid-attenuated inversion recovery (FLAIR) and double
inversion recovery (DIR) imaging is conducted in this article. The basics of the
two pulse sequences are first described, including the details of the inversion
preparation and imaging sequences with accompanying mathematical formulae for
choosing the inversion time in a variety of scenarios for use on clinical MRI
scanners. Magnetization preparation (or T2prep), a strategy for improving image
signal-to-noise ratio and contrast and reducing T1 weighting at high field
strengths, is also described. Lastly, image artifacts commonly associated with
FLAIR and DIR are described with clinical examples, to help avoid misdiagnosis.
LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
2017;46:1590-1600.
PMID- 28419604
TI - Predicting the difficulty of a transvenous lead extraction procedure: Validation
of the LED index.
AB - INTRODUCTION: A lead extraction difficulty (LED) score was proposed to predict
the difficult transvenous lead extraction (TLE) procedures, defined by means of
the fluoroscopy time. The aim of this study was to validate the estimation model
based on the LED index above 10 on an independent data set of TLE cases. METHODS:
Consecutive patients undergoing TLE between January 2014 and January 2016 were
included in this analysis. The fluoroscopy time related to the leads removal was
dichotomized as above or below its 90th percentile (PCTL). RESULTS: In total, 446
permanent leads were removed during 233 TLE procedures. Complete procedural
success was achieved in 232 (99.1%) patients. The LED index resulted >10 in
83(35.6%) procedures. Among these cases, 20 had fluoroscopy time above the 90th
PCTL (23.3 minutes) and were classified as true positive. Over the 150 procedures
with LED score <10, 147 were classified as true negative, and only 3 resulted
false negative. The sensitivity, the specificity, and the negative predictive
value of the LED index in predicting complex cases resulted 86.9 (confidence
interval [CI] 66.4-97.2)%, 70.0 (CI 63.3-76.1)%, and 98.0 (CI 94.3-99.6)%,
respectively. The multivariate logistic regression analysis confirmed a 12%
increased risk of high fluoroscopy for each additional point of the LED score (OR
1.12, CI 1.05-1.21, P = 0.001). CONCLUSION: The validation of the estimation
model based on the LED index <10 confirmed its high efficacy in predicting simple
TLE procedures.
PMID- 28419605
TI - Radiofrequency catheter ablation of atrial fibrillation: Electrical modification
suggesting transmurality is faster achieved with remote magnetic catheter in
comparison with contact force use.
AB - BACKGROUND: Remote magnetic navigation (RMN) and contact force (CF) sensing
catheters are available technologies for radiofrequency (RF) catheter ablation of
atrial fibrillation (AF). Our purpose was to compare time to electrogram (EGM)
modification suggesting transmural lesions between RMN and CF-guided AF ablation.
METHODS AND RESULTS: A total of 1,008 RF applications were analyzed in 21
patients undergoing RMN (n = 11) or CF-guided ablation (n = 10) for paroxysmal
AF. All procedures were performed in sinus rhythm during general anesthesia. Time
to EGM modification was measured until transmurality criteria were fulfilled: (1)
complete disappearance of R if initial QR morphology; (2) diminution > 75% of R
if initial QRS morphology; (3) complete disappearance of R' of initial RSR'
morphology. Impedance drop as well as force time integral (FTI) were also
assessed for each application. Mean CF at the beginning of each RF application in
the CF group was 11 +/- 2 g and mean FTI per application was 488 +/- 163 gs. Time
to EGM modification was significantly shorter in the RMN group (4.52 +/- 0.1
seconds vs. 5.6 +/- 0.09 seconds; P < 0.00001). There was no significant
difference between other procedural parameters. CONCLUSION: Remote magnetic AF
ablation is associated with faster EGM modification suggesting transmurality than
optimized CF and FTI-guided catheter ablation.
PMID- 28419603
TI - Assembly and activation of the Escherichia coli divisome.
AB - Cell division in Escherichia coli is mediated by a large protein complex called
the divisome. Most of the divisome proteins have been identified, but how they
assemble onto the Z ring scaffold to form the divisome and work together to
synthesize the septum is not well understood. In this review, we summarize the
latest findings on divisome assembly and activation as well as provide our
perspective on how these two processes might be regulated.
PMID- 28419606
TI - Stratified polygenic risk prediction model with application to CAGI bipolar
disorder sequencing data.
AB - Genetic data consists of a wide range of marker types, including common, low
frequency, and rare variants. Multiple genetic markers and their interactions
play central roles in the heritability of complex disease. In this study, we
propose an algorithm that uses a stratified variable selection design by genetic
architectures and interaction effects, achieved by a dataset-adaptive W-test. The
polygenic sets in all strata were integrated to form a classification rule. The
algorithm was applied to the Critical Assessment of Genome Interpretation 4
bipolar challenge sequencing data. The prediction accuracy was 60% using genetic
markers on an independent test set. We found that epistasis among common genetic
variants contributed most substantially to prediction precision. However, the
sample size was not large enough to draw conclusions for the lack of
predictability of low-frequency variants and their epistasis.
PMID- 28419608
TI - Multiple breath-hold proton spectroscopy of human liver at 3T: Relaxation times
and concentrations of glycogen, choline, and lipids.
AB - PURPOSE: To evaluate the feasibility of an expiration multiple breath-hold 1 H
MRS technique to measure glycogen (Glycg), choline-containing compounds (CCC),
and lipid relaxation times T1 , T2 , and their concentrations in normal human
liver. MATERIALS AND METHODS: Thirty healthy volunteers were recruited.
Experiments were performed at 3T. Multiple expiration breath-hold single-voxel
point-resolved spectroscopy (PRESS) technique was used for localization. Water
suppressed spectra were used for the estimation of Glycg, CCC, lipid methylene
(CH2 )n relaxation times and concentrations. Residual water lines were removed by
the Hankel Lanczos singular value decomposition filter. After phase correction
and frequency alignment, spectra were averaged and processed by LCModel. Summed
signals of Glycg resonances H2H4', H3, and H5 between 3.6 and 4 ppm were used to
estimate their apparent relaxation times and concentration. Glycg, CCC, and lipid
content were estimated from relaxation corrected spectral intensity ratios to
unsuppressed water line. RESULTS: Relaxation times were measured for liver Glycg
(T1 , 892 +/- 126 msec; T2 , 13 +/- 4 msec), CCC (T1 , 842 +/- 75 msec; T2 , 50
+/- 5 msec), lipid (CH2 )n (T1 , 402 +/- 19 msec; T2 , 52 +/- 3 msec), and water
(T1 , 990 +/- 89 msec; T2 , 30 +/- 2 msec). Mean CCC and lipid concentrations of
healthy liver were 7.8 +/- 1.3 mM and 15.8 +/- 23.6 mM, respectively. Glycg
content was found lower in the morning (48 +/- 21 mM) compared to the afternoon
(145 +/- 50 mM). CONCLUSION: Multiple breath-hold 1 H-MRS together with dedicated
postprocessing is a feasible technique for the quantification of liver Glycg,
CCC, and lipid relaxation times and concentrations. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:410-417.
PMID- 28419607
TI - Subjective and objective sleep quality modulate emotion regulatory brain function
in anxiety and depression.
AB - BACKGROUND: Disturbances in emotion regulation and sleep are shared across
anxiety and mood disorders. Poor sleep has been shown to impair cognitive
processes which may undermine cognitive regulatory function. However, it remains
unknown if sleep quality impacts regulatory mechanisms in clinical anxiety and
depression. METHODS: During fMRI, 78 patients with social anxiety disorder,
generalized anxiety disorder, and/or major depressive disorder completed a
validated emotion regulation task, which involved reappraisal (i.e., decrease
negative affect) as compared to viewing aversive images. Sleep quality was
assessed with the Pittsburgh Sleep Quality Index (PSQI) and actigraphy,
representing subjective and objective measures of sleep, respectively. Regression
analysis was conducted with the PSQI and actigraphy sleep efficiency, duration,
and wake-after sleep onset variables. RESULTS: PSQI and actigraphy measures
indicated that the majority of patients experienced problematic sleep, however,
subjective and objective sleep measures were uncorrelated. Whole-brain voxel-wise
regression analysis, controlling for diagnosis, revealed worse self-reported
sleep corresponded with less reappraise-related activation in the dorsal anterior
cingulate cortex (DACC). The same analysis performed with actigraphy data showed
less sleep efficiency positively corresponded with DACC activation. Post-hoc
stepwise regression analysis showed these sleep measures predicted DACC activity
whereas anxiety and depression symptoms did not. CONCLUSIONS: Individual
differences in self-perceived and objective sleep quality differentially
modulated the DACC, which is implicated in cognitive reappraisal. Findings
suggest neural correlates of emotion regulation tracks different aspects of the
sleep experience. Results also indicate sleep disturbance may play a role in the
emotion dysregulation observed in anxiety and depressive disorders.
PMID- 28419609
TI - Band-aids for Buchnera and B vitamins for all.
AB - Evolution lacks foresight, and hence, key adaptations may produce major
challenges over the long run. The natural world is rife with examples of long
term 'side effects' associated with quick-fix tinkering, including blind spots in
vertebrate eyes. An important question is how nature compensates for
imperfections once evolution has set a course. The symbioses associated with sap
feeding insects present a fascinating opportunity to address this issue. On one
hand, the substantial diversity and biomass of sap-feeding insects are largely
due to ancient acquisitions of nutrient-provisioning bacterial symbionts. Yet,
the insularity and small population sizes enforced by intracellular life and
strict maternal transfer inevitably result in the degradation of symbiont genomes
and, often, the beneficial services that symbionts provide. Stabilization through
lateral transfer of bacterial genes into the host nucleus (often from exogenous
sources) or replacement of the long-standing symbiont with a new partner are
potential solutions to this evolutionary dilemma (Bennett & Moran ). A third
solution is adoption of a cosymbiont that compensates for specific losses in the
original resident. Ancient 'co-obligate' symbiont pairs in mealybugs,
leafhoppers, cicadas and spittlebugs show colocalization, codiversification,
metabolite exchange and generally nonredundant nutrient biosynthesis (Bennett &
Moran ). But in this issue, Meseguer et al. () report on a different flavour of
cosymbiosis among conifer-feeding Cinara aphids.
PMID- 28419610
TI - Corrigendum.
PMID- 28419611
TI - Well-being therapy in depression: New insights into the role of psychological
well-being in the clinical process.
AB - A specific psychotherapeutic strategy for increasing psychological well-being and
resilience, well-being therapy (WBT), has been developed and validated in a
number of randomized controlled trials. The findings indicate that flourishing
and resilience can be promoted by specific interventions leading to a positive
evaluation of one's self, a sense of continued growth and development, the belief
that life is purposeful and meaningful, the possession of quality relations with
others, the capacity to manage effectively one's life, and a sense of self
determination. The evidence supporting the use of WBT and its specific
contribution when it is combined with other psychotherapeutic techniques is still
limited. However, the insights gained by the use of WBT may unravel innovative
approaches to assessment and treatment of mood and anxiety disorders, to be
confirmed by controlled studies, with particular reference to decreasing
vulnerability to relapse and modulating psychological well-being and mood. An
important characteristic of WBT is self-observation of psychological well-being
associated with specific homework. Such perspective is different from
interventions that are labeled as positive but are actually distress oriented.
Another important feature of WBT is the assumption that imbalances in well-being
and distress may vary from one illness to another and from patient to patient.
Customary clinical taxonomy and evaluation do not include psychological well
being, which may demarcate major prognostic and therapeutic differences among
patients who otherwise seem to be deceptively similar since they share the same
diagnosis.
PMID- 28419612
TI - Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping of talar
osteochondral lesions: Indicators of clinical outcomes.
AB - PURPOSE: To evaluate the utility of delayed gadolinium-enhanced magnetic
resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II
osteochondral lesions (OCLs) of the talus and define cutoff values for
identifying patients with good/poor clinical outcomes. MATERIALS AND METHODS: 28
patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5
years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n
= 16) treatment for type II OCL. Clinical outcomes were considered good with an
American Orthopedic Foot and Ankle Society score >=80. The T1 /T2 -values and
indices of repair tissue (RT; cartilage above the OCL) were compared to those of
the adjacent normal cartilage (NC) by region-of-interest analysis. The ability of
the two methods to discriminate RT from NC was determined by area under the
receiver operating characteristics curve (AUC) analysis. The Youden index was
maximized for T1 /T2 measures for identifying cutoff values indicative of
good/poor clinical outcomes. RESULTS: Repair tissue exhibited lower dGEMRIC
values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than
NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P =
0.0398). All T1 measures exhibited higher maximized Youden indices than the
corresponding T2 measures. The highest maximized Youden index for T1difference
was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%).
CONCLUSION: While T2 mapping is superior to dGEMRIC in discriminating RT, the
latter better identifies good/poor clinical outcomes in patients with type II
talar OCL. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson.
Imaging 2017;46:1601-1610.
PMID- 28419613
TI - PEG-poly(L-lysine)-based polymeric micelle MRI contrast agent: Feasibility study
of a Gd-micelle contrast agent for MR lymphography.
AB - PURPOSE: To investigate the feasibility of polymeric micelle of
poly(ethyleneglycol) (PEG)-b-poly(L-lysine-DOTA) (Gd-micelle) as a contrast agent
for magnetic resonance lymphography (MRL). MATERIALS AND METHODS: Twenty-four
female BALB/c mice were randomly divided into four groups of six mice each. Among
them, mice of two groups were injected of complete Freund's adjuvant to obtain
inflamed lymph nodes. We subcutaneously injected 0.5 MUmol Gd per mouse of Gd
micelle or gadofluorine P in the right rear footpad. Identical 3D T1 -weighted
gradient-echo imaging (1T MRI system) were subsequently obtained to create time
intensity curves of the right popliteal, sacral, and lumbar-aortic lymph nodes
and to measure the contrast ratios (CRs). The peak CR, area under the curve
(AUC), and elimination half-life (T1/2 ) of CR of the popliteal lymph node were
assessed by two-way factorial analysis of variance. We also performed a
qualitative assessment of normal and inflamed lymph node at three timepoints.
RESULTS: The mean peak CR of Gd-micelle was 2.64 and 1.89 for gadofluorine P in
normal mice, and 3.48 and 2.73 in the inflamed lymph node. Statistically, peak CR
was higher for Gd-micelle (P = 0.004). In addition, the AUC was larger (P <
0.001) and T1/2 was longer (P < 0.001) for Gd-micelle. In qualitative assessment,
Gd-micelle demonstrated the same or higher scores in every lymph node, and
demonstrated a higher score in lumbar-aortic lymph node of a 360-minute image (P
= 0.006) and in inflamed lymph node of a 360-minute image (P = 0.009).
CONCLUSION: Compared to gadofluorine P, Gd-micelle showed higher and more
prolonged enhancement in MRL imaging in normal and inflamed lymph nodes. LEVEL OF
EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:238-245.
PMID- 28419614
TI - Prospective comparison of biphasic contrast-enhanced CT, volume perfusion CT, and
3 Tesla MRI with diffusion-weighted imaging for insulinoma detection.
AB - PURPOSE: To evaluate the diagnostic performance of biphasic contrast-enhanced CT
(CECT), volume perfusion CT (VPCT) and 3 Tesla MRI with diffusion-weighted
imaging (DWI), in patients with clinically suspected insulinomas. MATERIALS AND
METHODS: This prospective study was approved by the institutional review board.
Sixty-four patients with clinically suspected insulinomas underwent biphasic
CECT, VPCT, and 3T MR with DWI. Two radiologists independently determined the
presence/absence of tumor using a 5-scale confidence level. Conspicuity of the
lesion and clarity of tumor-to-pancreatic duct distance were graded. Receiver
operating characteristic analysis was performed to compare diagnostic
performance. RESULTS: Forty-seven patients were tumor positive, with 51 tumors.
The differences between the areas under the curve values for tumor detection were
as follows: 0.715 (CECT), 0.903 (VPCT), 0.832 (MRI without DWI) and 0.955 (MRI
with DWI) for reader 1, and 0.738 (CECT), 0.895 (VPCT), 0.841 (MRI without DWI),
and 0.956 (MRI with DWI) for reader 2. MRI with DWI and VPCT were significantly
more accurate than CECT for insulinoma detection (P = 0.01 and 0.02 for reader 1,
and P = 0.01 and 0.03 for reader 2). Lesion conspicuity was better on MRI
compared with VPCT (P = 0.01), and both were better than CECT (both P < 0.01).
Tumor-to-pancreatic duct distance was better appreciated on MRI, compared with
CECT and VPCT (both P < 0.01). The weighted k values indicate good to excellent
agreement between observers for determining tumor presence/absence (k = 0.64
0.84). CONCLUSION: The 3T MRI with DWI and VPCT are significantly more accurate
than CECT for insulinoma detection. MRI demonstrates higher tumor conspicuity and
is superior in depicting the tumor-to-duct distance. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1648-1655.
PMID- 28419615
TI - Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of
SOCS genes, the negative regulators of cytokine signaling.
AB - The suppressor of cytokine signaling (SOCS) family has eight members and
suppresses various cytokine signaling pathways, including IFN signaling.
Therefore, some viruses have evolved molecular mechanisms for inducing SOCS
proteins and thus escaping host immunity. Herpes simplex virus type 1 (HSV-1) has
a mechanism for escaping from type I IFN by induction of both SOCS1 and SOCS3. In
this study, expression of the eight members of the SOCS family stimulated by HSV
1 infection was comparatively analyzed by qRT-PCR. It was found that SOCS1 and
SOCS3 are induced by HSV-1-infection at 4 hr post infection. However, such
induction was not observed in UL13 deficient virus-infected cells, suggesting
that UL13 protein kinase participates in induction of both genes. The
transcription factor Sp1-binding sites of SOCS3 promoter/enhancer region were
identified as the regulatory elements for induction of SOCS3 in HSV-1 infected
cells. Accumulation of activated Sp1 was detectable in the nuclei of HSV-1
infected cells before induction of SOCS3. Taken together, these results suggest
that HSV-1 has a potent mechanism for escaping from the IFN system.
PMID- 28419616
TI - The provision of pediatric cardiac anesthesia services in Germany: current status
of structural and personnel organization.
AB - BACKGROUND: Anesthesia for pediatric cardiac surgery requires a high level of
expert knowledge. There are currently no recommendations and standards for
anesthetic management for congenital cardiac surgery in Germany. AIM: The aim of
the present study was to assess the current status of structural and personnel
anesthetic standards at pediatric cardiac surgery centers in Germany. METHODS:
All cardiac surgical centers in Germany were reviewed for an active program for
congenital heart surgery. Centers with an active program were invited to respond
to an online survey. The questionnaire containing 55 items in 16 categories
assessed current practice in pediatric cardiac anesthesia. RESULTS: An active
program for pediatric cardiac surgery was identified at 27 centers. The response
rate to the survey was 96.3%. A specialized group of anesthesiologists for
pediatric cardiac anesthesia was reported from 26 centers (92.3%). The mean size
of this group was 4.8 anesthesiologists per center. However, the annual case load
of centers and relative annual case load per specialized anesthesiologist varied
considerably between 12.5 and 250. Nonanesthesiologists performed sedation and
general anesthesia for diagnostic and therapeutic interventions outside the
operating theater in children with congenital heart diseases in 24 centers (77%).
Although special equipment, for example, pediatric TEE, near-infrared
spectroscopy, and devices for mechanical auto transfusion were available in most
centers, their routine use was not always part of standard operating procedures.
The proposal for mean adequate training in pediatric cardiac anesthesia as
estimated by the participating centers was 10.8 months. CONCLUSION: The present
study represents the current structural situation for anesthesia at German
pediatric cardiac surgery centers.
PMID- 28419617
TI - Behavioural addiction and substance addiction should be defined by their
similarities not their dissimilarities.
PMID- 28419618
TI - Correspondence.
PMID- 28419619
TI - Palladium-Catalyzed Enantioselective Alkoxycarbonylation of Propargylic
Carbonates with (R)- or (S)-3,4,5-(MeO)3 -MeOBIPHEP.
AB - (R)- and (S)-3,4,5-(MeO)3 -MeOBIPHEP have been identified as the efficient chiral
ligands for the palladium-catalyzed highly enantioselective synthesis of 2,3
allenoates from different types of easily available racemic propargylic
carbonates with 90-98 % ee and decent yields. The potential of the products was
demonstrated with high chirality transfer efficiency.
PMID- 28419620
TI - Comparison of Emergency Department Patients to Inpatients Receiving a Pulmonary
Embolism Response Team (PERT) Activation.
AB - OBJECTIVES: The development of pulmonary embolism response teams (PERTs) has been
widely adopted nationally with the goal of providing multidisciplinary care to
patients with high-risk PE. Most PERT activations originate from the emergency
department (ED), while others are from the intensive care unit (ICU) or inpatient
floors. It is unclear if ED PERT activations differ from non-ED PERT activation
in terms of presentation, management, and outcome. METHODS: We enrolled a
consecutive cohort of patients for whom PERT was activated at an urban academic
medical center. We compared three groups of PERT activations based on whether the
activation originated from the ED, ICU, or a non-ICU inpatient floor. We compared
these groups in terms of the proportion of PERT activations that occurred during
day, evening, or weekend hours and the proportion of confirmed PE. We also
compared PE severity, treatment, and outcomes across locations. We tested
differences using chi-square tests, with a two-tailed p-value of <0.05 considered
statistically significant. RESULTS: We enrolled 561 patients, of whom 449 (79.5%)
had confirmed PE. The mean +/- SD age of patients with confirmed PE was 61 +/- 17
years, and 300 (53.5%) were male. Activations from the ED (n = 283, 88.4%) or
floor (n = 100, 74.6%) were more likely to be for confirmed PE than activations
from the ICU (n = 63, 58.9%; p < 0.0001). There was a statistical difference in
the time of day of PERT activation with the ED having more activations during
night hours than the ICU or floors (p = 0.004). Most activations for confirmed,
massive PE originated from the ICU (n = 41, 65.1%), followed by the ED (n = 82,
29%) and inpatient floors (n = 22, 22%; p < 0.0001). Most activations from the ED
(n = 155, 54.8%) and floors (n = 55, 55%) were for submassive PE. The use of
thrombolysis or thrombectomy was more common among ICU patients (n = 18, 33.3%),
followed by ED patients (n = 53, 19.6%) and then floor patients (n = 8, 8.2%).
Mortality and major bleeding events were most common among ICU patients and
similar among ED and floor patients. CONCLUSIONS: Pulmonary embolism response
team activations from different clinical locations differ in terms of patient
presentation, PE confirmation, treatments, and outcomes. PERTs should be
customized to support the different needs of each clinical area.
PMID- 28419621
TI - The feasibility, acceptability, and outcomes of PRIME-D: A novel mobile
intervention treatment for depression.
AB - BACKGROUND: Despite decades of research and development, depression has risen
from the fifth to the leading cause of disability in the United States. Barriers
to progress in the field are (1) poor access to high-quality care; (2) limited
mental health workforce; and (3) few providers trained in the delivery of
evidence-based treatments (EBTs). Although mobile platforms are being developed
to give consumers greater access to high-quality care, too often these tools do
not have empirical support for their effectiveness. In this study, we evaluated
PRIME-D, a mobile app intervention that uses social networking, goal setting, and
a mental health coach to deliver text-based, EBT's to treat mood symptoms and
functioning in adults with depression. METHODS: Thirty-six adults with depression
remotely participated in PRIME-D over an 8-week period with a 4-week follow-up,
with 83% retained over the 12-week course of thestudy. RESULTS: On average,
participants logged into the app 5 days/week. Depression scores (PHQ-9)
significantly improved over time (over 50% reduction), with coach interactions
enhancing these effects. Mood-related disability (Sheehan Disability Scale (SDS))
also significantly decreased over time with participants no longer being impaired
by their mood symptoms. Overall use of PRIME-D predicted greater gains in
functioning. Improvements in mood and functioning were sustained over the 4-week
follow-up. CONCLUSIONS: Results suggest that PRIME-D is a feasible, acceptable,
and effective intervention for adults with depression and that a mobile service
delivery model may address the serious public health problem of poor access to
high-quality mental health care.
PMID- 28419622
TI - Quantitative depth resolved microcirculation imaging with optical coherence
tomography angiography (Part Iota): Blood flow velocity imaging.
AB - The research goal of the microvascular network imaging with optical coherence
tomography (OCT) angiography is to achieve depth resolved blood flow and vessel
imaging in vivo in the clinical management of patents. In this review, we review
the main phenomena that have been explored in OCT to image the blood flow
velocity vector and the vessels of the microcirculation within living tissues.
Parameters that limit the accurate measurements of blood flow velocity are then
condisered. Finally, initial Clinic diagnosis applications of and future
developments are discussed. This article is protected by copyright. All rights
reserved.
PMID- 28419623
TI - Cognitive component of psychomotor retardation in unipolar and bipolar
depression: Is verbal fluency a relevant marker? Impact of repetitive
transcranial stimulation.
AB - AIMS: In the literature, psychomotor retardation (PMR) is increasingly
highlighted as a relevant marker for depression. Currently, we chose to focus on
the fluency capacities as an evaluation of the frontal lobes functioning to reach
a better understanding of cognitive and neurobiological mechanisms involved in
PMR in depression. The aims of this study were: (i) to explore the cognitive
component of PMR through the analysis of verbal fluency (VF) performance in
unipolar and bipolar depression; and (ii) to examine whether a repetitive
transcranial magnetic stimulation treatment could improve concomitantly the PMR
and VF capacities, as a relevant marker characteristic of the cognitive component
of PMR. METHODS: Fifteen unipolar and 15 bipolar patients were compared to 15
healthy adults. Before treatment, the results showed VF deficits, particularly
marked in the bipolar group. The investigation of the interplay between PMR, VF
performance, Montgomery-Asberg Depression Rating Scale scores, and Montreal
Cognitive Assessment scores showed that the deficits in these various dimensions
were not homogeneous. RESULTS: The absence of correlation between the psychomotor
retardation scale (the French Retardation Rating Scale for Depression) and VF,
and the correlation with MoCA raise the hypothesis of a more global cognitive
impairment associated with PMR in the BD group. The repetitive transcranial
magnetic stimulation treatment had a positive impact on depression, PMR, and
fluency scores. CONCLUSION: Correlations between the Retardation Rating Scale for
Depression and VF performances appeared after treatment, showing the cognitive
role of psychomotor functioning in depression. Further analyses, including other
cognitive measures in an objective evaluation of PMR, are required for a better
understanding of these complex relationships.
PMID- 28419624
TI - The effect of single oral doses of duloxetine, reboxetine, and midodrine on the
urethral pressure in healthy female subjects, using urethral pressure
reflectometry.
AB - AIMS: To evaluate the effect on urethral pressure of reference drugs known to
reduce stress urinary incontinence symptoms by different effect size and
mechanisms of action on urethral musculature under four test conditions in
healthy female subjects using urethral pressure reflectometry. METHODS: Healthy
females aged 18-55 years were recruited by advertising for this phase 1, single
site, placebo-controlled, randomized, four-period, crossover study. The
interventions were single oral doses of 10 mg Midodrine, 80 mg Duloxetine, 12 mg
Reboxetine, and placebo. The endpoints were the opening urethral pressure
measured in each period at four time points (predose and 2, 5.5, and 9 h after
dosing). RESULTS: Twenty-nine females were enrolled; 25 randomized and 24
completed the study. The opening urethral pressure was higher in all measurements
with filled bladder compared with empty bladder, and during squeezing compared to
the resting condition. All three drugs increased the opening urethral pressure
during all four conditions with a ranking of their effect on urethral pressure
matching their reported clinical effect (difference vs. placebo at their reported
time of peak plasma concentrations [Tmax ] during resting with filled bladder:
Midodrine 9.3 cmH2 O [95%CI 3.0, 15.5], Duloxetine 24.2 cmH2 O [95%CI 17.9,
30.5], and Reboxetine 44.9 cmH2 O [95% CI 40.2, 52.8] cmH2 O). CONCLUSIONS:
Urethral pressure reflectometry is capable of detecting drug-induced changes in
urethral tone in various conditions. The magnitude of drug-induced changes by the
test drugs seems to match their clinical profile and differences in mode of
action.
PMID- 28419625
TI - Meta-analysis of interventions for posttraumatic stress disorder and depression
in adult survivors of mass violence in low- and middle-income countries.
AB - BACKGROUND: Most survivors of mass violence live in low- and middle-income
countries (LMICs). We conducted a meta-analysis of randomized controlled
psychotherapy trials for adult posttraumatic stress disorder (PTSD) and/or
depression in LMICs. METHODS: We included 18 clinical trials (3,058
participants), in which 25 and 18 treatment arms measured symptoms of PTSD and
depression, respectively. RESULTS: Active treatments for PTSD yielded a large
aggregated pre-post effect size (g = 1.29; 95% CI = [0.99; 1.59]) and a small to
medium effect size at posttreatment when compared to control conditions (g =
0.39; 95% CI = [0.24; 0.55]). Effect sizes were similar for pretreatment versus
follow-up (g = 1.75; 95% CI = [1.17; 2.32]) and in comparison to waitlist at
follow-up (g = 0.93; 95% CI = [0.56; 1.31]). Active treatments for depression
produced large pre-post (g = 1.28; 95% CI = [0.96; 1.61]) and controlled effect
sizes (posttreatment, comparison to control conditions, g = 0.86; 95% CI = [0.54;
1.18]). CONCLUSIONS: Our findings suggest that psychological interventions can
effectively reduce symptoms of PTSD and depression in LMICs. Future research
needs to focus on cost-effective interventions that are likely to be disseminated
to the large numbers of war survivors in LMICs.
PMID- 28419626
TI - Influence of job demands and job control on work-life balance among Taiwanese
nurses.
AB - AIM: This study investigated the extent to which the job demands and job control
of nurses were related to their work-life balance. BACKGROUND: The inability to
achieve work-life balance is one of the major reasons for the declining retention
rate among nurses. Job demands and job control are two major work domain factors
that can have a significant influence on the work-life balance of nurses. METHOD:
The study measured the job demands, job control and work-life balance of 2040
nurses in eight private hospitals in Taiwan in 2013. RESULTS: Job demands and job
control significantly predicted all the dimensions of work-life balance. Job
demands increased the level of work-life imbalance among nurses. While job
control showed positive effects on work/personal life enhancement, it was found
to increase both work interference with personal life and personal life
interference with work. CONCLUSION: Reducing the level of job demands
(particularly for psychological demands) between family and career development
and maintaining a proper level of job control are essential to the work-life
balance of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Flexible work practices
and team-based management could be considered by nursing management to lessen job
demand pressure and to facilitate job engagement and participation among nurses,
thus promoting a better balance between work and personal life.
PMID- 28419627
TI - Instantaneous Conversion of [11 C]CO2 to [11 C]CO via Fluoride-Activated Disilane
Species.
AB - The development of a fast and novel methodology to generate carbon-11 carbon
monoxide ([11 C]CO) from cyclotron-produced carbon-11 carbon dioxide ([11 C]CO2 )
mediated by a fluoride-activated disilane species is described. This methodology
allows up to 74 % conversion of [11 C]CO2 to [11 C]CO using commercially
available reagents, readily available laboratory equipment and mild reaction
conditions (room temperature). As proof of utility, radiochemically pure
[carbonyl-11 C]N-benzylbenzamide was successfully synthesized from produced [11
C]CO in up to 74 % radiochemical yield (RCY) and >99 % radiochemical purity (RCP)
in <=10 min from end of [11 C]CO2 delivery.
PMID- 28419628
TI - HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data.
AB - The accurate typing of human leukocyte antigen (HLA) alleles is critical for a
variety of medical applications, such as genomic studies of multifactorial
diseases, including immune system and inflammation-related disorders, and donor
selection in organ transplantation and regenerative medicine. Here, we developed
a new algorithm for determining HLA alleles using next-generation sequencing
(NGS) results. The method consists of constructing an extensive dictionary of HLA
alleles, precise mapping of the NGS reads, and calculating a score based on
weighted read counts to select the most suitable pair of alleles. The developed
algorithm compares the score of all allele pairs, taking into account variation
not only in the domain for antigen presentation (G-DOMAIN), but also outside this
domain. Using this method, HLA alleles could be determined with 6-digit
precision. We showed that our method was more accurate than other NGS-based
methods and revealed limitations of the conventional HLA typing technologies.
Furthermore, we determined the complete genomic sequence of an HLA-A-like
pseudogene when we assembled NGS reads that had caused arguable typing, and found
its identity with HLA-Y*02:01. The accuracy of the HLA-A allele typing was
improved after the HLA-Y*02:01 sequence was included in the HLA allele
dictionary.
PMID- 28419630
TI - Correction.
PMID- 28419629
TI - Motivational and behavioural models of change: A longitudinal analysis of change
among men with chronic haemophilia-related joint pain.
AB - BACKGROUND: Motivational and behavioural models of adjustment to chronic pain
make different predictions about change processes, which can be tested in
longitudinal analyses. METHODS: We examined changes in motivation, coping and
acceptance among 78 men with chronic haemophilia-related joint pain. Using cross
lagged regression analyses of changes from baseline to 6 months as predictors of
changes from 6 to 12 months, with supplementary structural equation modelling, we
tested two models in which motivational changes influence behavioural changes,
and one in which behavioural changes influence motivational changes. RESULTS:
Changes in motivation to self-manage pain influenced later changes in pain
coping, consistent with the motivational model of pain self-management, and also
influenced later changes in activity engagement, the behavioural component of
pain acceptance. Changes in activity engagement influenced later changes in pain
willingness, consistent with the behavioural model of pain acceptance.
CONCLUSIONS: Based on the findings, a combined model of changes in pain self
management and acceptance is proposed, which could guide combined interventions
based on theories of motivation, coping and acceptance in chronic pain.
SIGNIFICANCE: This study adds longitudinal evidence about sequential change
processes; a test of the motivational model of pain self-management; and tests of
behavioural versus motivational models of pain acceptance.
PMID- 28419631
TI - TgPL2, a patatin-like phospholipase domain-containing protein, is involved in the
maintenance of apicoplast lipids homeostasis in Toxoplasma.
AB - Patatin-like phospholipases are involved in numerous cellular functions,
including lipid metabolism and membranes remodeling. The patatin-like catalytic
domain, whose phospholipase activity relies on a serine-aspartate dyad and an
anion binding box, is widely spread among prokaryotes and eukaryotes. We describe
TgPL2, a novel patatin-like phospholipase domain-containing protein from the
parasitic protist Toxoplasma gondii. TgPL2 is a large protein, in which the key
motifs for enzymatic activity are conserved in the patatin-like domain. Using
immunofluorescence assays and immunoelectron microscopy analysis, we have shown
that TgPL2 localizes to the apicoplast, a non-photosynthetic plastid found in
most apicomplexan parasites. This plastid hosts several important biosynthetic
pathways, which makes it an attractive organelle for identifying new potential
drug targets. We thus addressed TgPL2 function by generating a conditional
knockdown mutant and demonstrated it has an essential contribution for
maintaining the integrity of the plastid. In absence of TgPL2, the organelle is
rapidly lost and remaining apicoplasts appear enlarged, with an abnormal
accumulation of membranous structures, suggesting a defect in lipids homeostasis.
More precisely, analyses of lipid content upon TgPL2 depletion suggest this
protein is important for maintaining levels of apicoplast-generated fatty acids,
and also regulating phosphatidylcholine and lysophosphatidylcholine levels in the
parasite.
PMID- 28419632
TI - Factors influencing beliefs about intimate partner violence among adults in South
Korea.
AB - OBJECTIVES: This study aimed to identify factors influencing beliefs about
intimate partner violence among Korean adults. DESIGN AND SAMPLE: This is a cross
sectional descriptive study that analyzed data from 466 adults. MEASURES: Beliefs
about intimate partner violence were measured using a self-report questionnaire
with a total of 28 items consisting of four subscales: perpetrator's
justification for beating women, blaming women for violence against them,
perpetrator's responsibility for violence, and giving help to victims. RESULTS:
Men and women had significantly different beliefs about intimate partner violence
(t = -7.19, p < .001). Some characteristics were identified that led to unhealthy
beliefs about intimate partner violence. Four variables-gender, age, educational
level, and witnessing parental violence-had an explanatory power of 20% with
regard to beliefs about IPV (F = 10.50, p = .000). CONCLUSIONS: In South Korea,
men, older individuals, and those with less formal education or who have
witnessed parental violence need education to foster healthier beliefs about
intimate partner violence. Nurses can play a vital role in efforts to decrease
intimate partner violence.
PMID- 28419633
TI - BK virus in solid organ transplantation: Pretransplant screening of recipients
and risk factors for disease.
PMID- 28419634
TI - Contrast-Enhanced Ultrasound and Elastography Imaging of the Neonatal Brain: A
Review.
AB - Neonates presenting with neurologic symptoms require rapid, noninvasive imaging
with high spatial resolution and tissue contrast. Magnetic resonance imaging
(MRI) is currently the most sensitive and specific imaging modality for
evaluation of neurological pathology. This modality does come with several
challenges in the neonatal population, namely, the need to transport a possibly
critically sick neonate to the MRI suite and the necessity of the neonate to
remain still for a significant length of time, occasionally requiring sedation.
Cranial ultrasound has provided radiologists and clinicians with an invaluable
imaging modality that allows of rapid, bedside point of care evaluation without
ionizing radiation. The major drawback of cranial ultrasound is its lower
sensitivity and specificity for subtle/early lesions. Contrast-enhanced
ultrasound (CEUS) and elastography have the potential to improve sensitivity and
specificity for a variety of neuropathology but also expand the indications for
cranial ultrasound. Goal of this paper is to present and discuss CEUS and
elastography for neonatal brain imaging.
PMID- 28419635
TI - Canine histiocytic sarcoma presenting as a target lesion on brain magnetic
resonance imaging and as a solitary pulmonary mass.
AB - A 6-year-old spayed female miniature schnauzer presented with generalized
seizures and progressive multifocal intracranial neurologic disease. Thoracic
radiographs and computed tomography (CT) revealed a large solitary pulmonary mass
within the right cranial lung lobe. On brain magnetic resonance imaging (MRI), a
solitary intraparenchymal mass within the left piriform lobe had a "target"
appearance on both pre- and postcontrast sequences. Cerebrospinal fluid was
unremarkable and histopathology indicated both masses represented histiocytic
sarcoma. This case represents an uncommonly reported MRI appearance of
histiocytic sarcoma in the canine brain and a large, solitary-appearing pulmonary
histiocytic sarcoma in the same dog.
PMID- 28419636
TI - A case of solitary pulmonary capillary hemangioma indicating true gross
appearance.
PMID- 28419637
TI - Self-reported prevalence, description and management of pain in adults with
haemophilia: methods, demographics and results from the Pain, Functional
Impairment, and Quality of life (P-FiQ) study.
AB - INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to
acute/chronic joint pain. AIM: To assess self-reported prevalence, description
and management of pain in adult males with mild-to-severe haemophilia and history
of joint pain/bleeding. METHODS: Participants completed a pain survey and five
patient-reported outcome instruments assessing pain, functional impairment and
health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled,
median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65%
were overweight/obese. Many (56%) were not receiving routine infusions; 30% never
received routine infusions. During the prior 6 months, 20% experienced acute
pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both
acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed
(30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual
analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities
List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during
the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti
inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice
(65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common
opioid for both acute/chronic pain (30%); other long-acting opioids were
infrequently used specifically for chronic but not acute pain (morphine, 7%;
methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain,
particularly those with both acute/chronic pain, frequently experience
psychological issues, functional disability and reduced HRQoL. Treatment
strategies for acute pain (e.g. routine infusions to prevent bleeding) and for
chronic pain (e.g. long-acting opioids) may be underused.
PMID- 28419638
TI - Diffusion tensor imaging tractography study in bipolar disorder patients compared
to first-degree relatives and healthy controls.
AB - AIM: We aimed to compare white matter structural changes in specific tracts by
diffusion tensor imaging (DTI) tractography in patients with bipolar disorder
(BD) I, non-ill first-degree relatives (FDR) of the patients, and healthy
controls (HC). METHODS: In a cross-sectional study, we studied right-handed
subjects consisting of 16 euthymic BD I patients, 15 FDR, and 15 HC. The anterior
thalamic radiation, uncinate fasciculus, corpus callosum, and cingulum bundle
were reconstructed by DTI tractography. Mean fractional anisotropy (FA) and
apparent diffusion coefficient (ADC) values were compared for group differences
followed by post-hoc analysis. RESULTS: The three groups did not differ in terms
of sociodemographic variables. There were significant group differences in the FA
values among the BD I patients, their FDR, and the HC for the corpus callosum,
the dorsal part of the right cingulum bundle, the hippocampal part of the
cingulum bundle bilaterally, and the uncinate fasciculus (P < 0.001). The FA
values in the patients were significantly lower than in controls, and FDR also
showed similar differences; however, they were smaller than those in patients. No
significant difference was found between the groups for FA values of the dorsal
part of the left cingulum bundle and anterior thalamic radiation. Significant
differences were present for ADC values among the groups for the corpus callosum,
the dorsal and hippocampal parts of the cingulum, anterior thalamic radiation,
and uncinate fasciculus bilaterally (P < 0.01). The FA and ADC values did not
correlate significantly with age or any clinical variables. CONCLUSION: These
findings suggest that BD patients and their FDR show alterations in
microstructural integrity of white matter tracts, compared to the healthy
population.
PMID- 28419639
TI - Differences in intraoperative hemodynamics between spinal and general anesthesia
in infants undergoing pyloromyotomy.
AB - BACKGROUND: Hypotension and bradycardia are known side effects of spinal
anesthesia in pregnant women undergoing cesarean section and adults undergoing
other surgical procedures. Whether children experience similar hemodynamic
changes is unclear. AIMS: The purpose of this study is to evaluate hemodynamic
effects of spinal anesthesia compared to general anesthesia in a cohort of
healthy infants. METHODS: The University of Vermont Medical Center almost
exclusively used spinal anesthesia for infant pyloromyotomy surgery between 2008
and 2013, while Columbia University Medical Center relied on general anesthesia.
The primary outcome assessed was the percentage change in intraoperative heart
rate and blood pressure (systolic [SBP] and mean [MAP] blood pressure) from
baseline. Analysis was performed using t-tests for continuous variables, followed
by linear regression to account for differences in demographic and clinical
covariates. RESULTS: The study sample consisted of 51 infants with spinal
anesthesia at the University of Vermont and 52 infants with general anesthesia at
Columbia University. The decrease from baseline for mean intraoperative SBP was
8.2 +/- 16.8% for spinal anesthesia and -24.2 +/- 17.2% for general anesthesia
(difference between means: 16.2% [95% confidence interval (CI), 9.5-22.9]), while
the decrease from baseline for mean intraoperative MAP was -16.3 +/- 19.9% for
spinal anesthesia and -24.6 +/- 19.3% for general anesthesia (difference between
means: 8.4% [95% CI, 0.8-16]). Spinal anesthesia patients also had smaller drops
in minimum intraoperative MAP and SBP. These blood pressure differences persisted
even after adjusting for covariates. No differences in heart rate were seen
between spinal and general anesthesia. DISCUSSION: Our findings show that spinal
anesthesia performed in healthy infants undergoing pyloromyotomy results in
reduced intraoperative blood pressure changes from baseline, significantly higher
blood pressure readings, and no increased bradycardia compared to general
anesthesia. Further research is needed to assess whether any clinical impact of
these hemodynamic differences between spinal and general anesthesia exists.
PMID- 28419640
TI - Relationships between dispositional mindfulness, self-acceptance, perceived
stress, and psychological symptoms in advanced gastrointestinal cancer patients.
AB - OBJECTIVE: Previous studies have shown that dispositional mindfulness is
associated with less psychological symptoms in cancer patients. The present study
investigated how dispositional mindfulness is related to psychological symptoms
in advanced gastrointestinal cancer patients by considering the roles of self
acceptance and perceived stress. METHODS: A total of 176 patients with advanced
gastrointestinal cancer were recruited to complete a series of questionnaires
including Mindfulness Attention Awareness Scale, Self-acceptance Questionnaire,
Chinese Perceived Stress Scale, and General Health Questionnaire. RESULTS:
Results showed that the proposed model fitted the data very well (chi2 = 7.564,
df = 7, P = .364, chi2 /df = 1.094, Goodness of Fit Index (GFI) = 0.986,
Comparative Fit Index (CFI) = 0.998, Tucker Lewis Index (TLI) = 0.995, Root Mean
Square Error of Approximation (RMSEA) = 0.023). Further analyses revealed that,
self-acceptance and perceived stress mediated the relation between dispositional
mindfulness and psychological symptoms (indirect effect = -0.052, 95% confidence
interval = -0.087 ~ -0.024), while self-acceptance also mediated the relation
between dispositional mindfulness and perceived stress (indirect effect = -0.154,
95% confidence interval = -0.261 ~ -0.079). CONCLUSIONS: Self-acceptance and
perceived stress played critical roles in the relation between dispositional
mindfulness and psychological symptoms. Limitations, clinical implications, and
directions for future research were discussed.
PMID- 28419641
TI - Neural correlates of experimental trauma memory retrieval.
AB - OBJECTIVES: Traumatic memories such as intrusions and flashbacks play a major
role in the development and maintenance of post-traumatic stress disorder (PTSD).
A thorough understanding of the neural mechanisms underlying traumatic memories
is indispensable for precise diagnosis, for personalized treatment and
prevention. In particular, the identification of early neural predictor variables
for intrusion development shortly after trauma exposure requires detailed
investigation. EXPERIMENTAL DESIGN: Here, we examined the neural correlates of
early experimental trauma memory retrieval in a traumatic film paradigm in 42
young healthy females, using both implicit and explicit retrieval tasks.
PRINCIPAL OBSERVATIONS: We show that implicit experimental trauma retrieval
specifically involved the retrosplenial cortex and the anterior cingulate cortex
(ACC), while both retrieval tasks resulted in trauma-related activity in the
posterior cingulate cortex (PCC) and the precuneus. Importantly, neural activity
early after experimental trauma exposure predicted later intrusion development,
with independent contributions from activity in the retrosplenial cortex
(implicit retrieval) and the PCC (explicit retrieval). Additional analyses
revealed a stronger connectivity between the bilateral amygdala and the
supplementary motor area, precentral and paracentral lobule for the control group
compared to the experimental trauma group. CONCLUSIONS: Our study gives new
insights in the neural correlates of experimental trauma memory retrieval and
their predictive value for subsequent symptom development. Our results could
provide the basis for personalized early treatment and prevention of PTSD. Hum
Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419642
TI - Nicotine-induced molecular alterations are modulated by GABAB receptor activity.
AB - It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward
effect; nevertheless, the mechanism implicated is not well known. In this regard,
we evaluated the involvement of GABAB receptors on the behavioral, neurochemical,
biochemical and molecular alterations associated with the rewarding effects
induced by NIC in mice, from a pharmacological and genetic approach. NIC-induced
rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by
conditioned place preference (CPP) paradigm. CPP has three phases:
preconditioning, conditioning and postconditioning. GABAB receptor antagonist 2
hydroxysaclofen (0.25, 0.5 and 1 mg/kg; intraperitoneally, ip) or the GABAB
receptor agonist baclofen (3 mg/kg; ip) was injected before NIC during the
conditioning phase. GABAB1 knockout (GABAB1 KO) mice received NIC during the
conditioning phase. Vehicle and wild-type controls were employed. Neurochemical
(dopamine, serotonin and their metabolites), biochemical (nicotinic receptor
alpha4beta2, alpha4beta2nAChRs) and molecular (c-Fos) alterations induced by NIC
were analyzed after the postconditioning phase by high-performance liquid
chromatography (HPLC), receptor-ligand binding assays and immunohistochemistry,
respectively, in nucleus accumbens (Acb), prefrontal cortex (PFC) and ventral
tegmental area (VTA). NIC induced rewarding effects in the CPP paradigm and
increased dopamine levels in Acb and PFC, alpha4beta2nAChRs density in VTA and c
Fos expression in Acb shell (AcbSh), VTA and PFC. We showed that behavioral,
neurochemical, biochemical and molecular alterations induced by NIC were
prevented by baclofen. However, in 2-hydroxysaclofen pretreated and GABAB1 KO
mice, these alterations were potentiated, suggesting that GABAB receptor activity
is necessary to control alterations induced by NIC-induced rewarding effects.
Therefore, the present findings provided important contributions to the
mechanisms implicated in NIC-induced rewarding effects.
PMID- 28419643
TI - Post-lunch triglyceridaemia associates with HDLc and insulin resistance in
fasting normotriglyceridaemic menopausal women.
AB - OBJECTIVES: Post-prandial hypertriglyceridaemia (P-HTG) is associated with
cardiovascular disease. This association is of paramount importance during
menopause, which is also related to reduced high-density lipoprotein-cholesterol
(HDLc) and elevated triglyceride (TG) levels. We aimed to provide a self-assesing
tool to screen for P-HTG in menopausal women who were normotriglyceridaemic at
fasting and adhered to a Mediterranean-style eating pattern. METHODS: We
performed oral fat loading tests (OFLT) in combination with self-measurements of
diurnal capillary TG at fixed time-points (DC-TG) in 29 healthy menopausal women.
TG levels >220 mg dL-1 at any given time during the OFLT served as diagnostic
criteria for P-HTG. Subsequently, DC-TG profiles were examined to determine the
best mealtime (breakfast, lunch or dinner), as well as optimal cut-off points to
classify these women as having P-HTG according to the OFLT. Insulin resistance
was defined as the upper tertile of the homeostatic model assessment of insulin
resistance. RESULTS: We found that, despite having normal fasting TG levels, P
HTG was highly prevalent (approximately 40%). Moreover, self-assessed 3-h post
lunch TG levels >165 mg dL-1 increased the odds of having hypo-HDL
cholesterolaemia by 14.1-fold (P = 0.026) and the odds of having insulin
resistance by 31.6-fold (P = 0.007), adjusted for total fat intake in women
adhering to a Mediterranean eating pattern having their highest energy intake at
lunch. CONCLUSIONS: Self-assessed 3-h post-lunch TG can be used to study post
prandial TG metabolism in Southern European menopausal women who are
normotriglyceridaemic at fasting. Characterising an individual's post-prandial
response may help menopausal women to evaluate their risk of cardiovascular
disease.
PMID- 28419644
TI - Diffusion-weighted imaging of hyperpolarized [13 C]urea in mouse liver.
AB - PURPOSE: To compare the apparent diffusion coefficient (ADC) of hyperpolarized
(HP) [13 C,15 N]urea to the ADC of endogenous water in healthy and fibrotic mouse
liver. MATERIALS AND METHODS: ADC measurements for water and [13 C]urea were made
in agarose phantoms at 14.1T. Next, the ADC of water and injected HP [13 C,15
N]urea were measured in eight CD1 mouse livers before and after induction of
liver fibrosis using CCl4 . Liver fibrosis was quantified pathologically using
the modified Brunt fibrosis score and compared to the measured ADC of water and
urea. RESULTS: In cell-free phantoms with 12.5% agarose, water ADC was nearly
twice the ADC of urea (1.93 * 10-3 mm2 /s vs. 1.00 * 10-3 mm2 /s). The mean ADC
values of water and [13 C,15 N]urea in healthy mouse liver (+/-SD) were nearly
identical [(0.75 +/- 0.11) * 10-3 mm2 /s and (0.75 +/- 0.22) * 10-3 mm2 /s,
respectively]. Mean water and [13 C,15 N]urea ADC values in fibrotic liver (+/
SD) were (0.84 +/- 0.22) * 10-3 mm2 /s and (0.75 +/- 0.15) * 10-3 mm2 /s,
respectively. Neither water nor urea ADCs were statistically different in the
fibrotic livers compared to baseline (P = 0.14 and P = 0.99, respectively). Water
and urea ADCs were positively correlated at baseline (R2 = 0.52 and P = 0.045)
but not in fibrotic livers (R2 = 0.23 and P = 0.23). CONCLUSION: ADC of injected
hyperpolarized urea in healthy liver reflects a smaller change as compared to
free solution than ADC of water. This may reflect differences in cellular
compartmentalization of the two compounds. No significant change in ADC of either
water or urea were observed in relatively mild stages of liver fibrosis. LEVEL OF
EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:141-151.
PMID- 28419645
TI - Diagnostic performance of different imaging modalities in the assessment of
distant metastasis and local recurrence of tumor in patients with non-small cell
lung cancer.
AB - PURPOSE: To compare the diagnostic performance of positron emission tomography
with [18F] fluoro-2-deoxy-glucose (FDG-PET) coregistered with magnetic resonance
imaging (FDG-PET/MRI), MRI with and without diffusion-weighted imaging (DWI), FDG
PET fused with computed tomography (FDG-PET/CT) with brain contrast-enhanced (CE
) MRI, and routine radiological examination for assessment of postoperative
recurrence in nonsmall-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS:
96 consecutive postoperative NSCLC patients (52 men, 44 women; mean age 72 years)
prospectively underwent whole-body 3T MRI with and without DWI; PET/CTs and
routine radiological examinations consisted of CE-brain MRI, whole-body CE-CT,
and bone scintigraphy. The patients were divided into a recurrence (n = 17) and a
nonrecurrence (n = 79) group based on pathological and follow-up examinations.
All coregistered PET/MRIs were generated by proprietary software. The probability
of recurrence was visually assessed on a per-patient basis. Receiver operating
characteristic analyses were used to compare the diagnostic performance of all
methods. Finally, diagnostic capabilities were compared by means of McNemar's
test. RESULTS: Areas under the curves (Azs) were significantly larger for PET/MRI
and whole-body MRI with DWI (Az = 0.99) than for PET/CT (Az = 0.92, P < 0.05) and
conventional radiological examination (Az = 0.91, P < 0.05). Specificity and
accuracy of PET/MRI and MRI with and without DWI were significantly higher than
those of PET/CT (P < 0.05) and routine radiological examination (P < 0.05).
CONCLUSION: Whole-body FDG-PET/MRI and MRI with DWI were found to be more
specific and accurate than FDG-PET/CT and routine radiological examinations for
assessment of recurrence in NSCLC patients, although MRI with and without DWI
demonstrated slightly lower sensitivity than PET/CT. LEVEL OF EVIDENCE: 2
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1707-1717.
PMID- 28419646
TI - Suvorexant, an orexin/hypocretin receptor antagonist, attenuates motivational and
hedonic properties of cocaine.
AB - Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that
project to structures implicated in reward and emotion processing. Converging
evidence demonstrates functional roles of orexin signaling in arousal,
sleep/wakefulness and motivated behaviors for natural and drug rewards.
Suvorexant, a dual orexin receptor antagonist, recently received approval from
the US Food and Drug Administration to treat insomnia. In Experiment 1, rats self
administered cocaine under a progressive-ratio schedule of reinforcement and the
effects of suvorexant on motivation to self-administer cocaine were measured. In
Experiment 2, the effects of suvorexant on cocaine reward were assessed by using
a place conditioning paradigm, and 50-kHz ultrasonic vocalizations were also
recorded to track changes in hedonic reactivity to cocaine. To rule out
potentially confounding effects of suvorexant-induced somnolence, locomotor
activity was also measured. In Experiment 3, the effects of suvorexant on cocaine
evoked elevations in ventral striatal dopamine were examined. Data reveal that
suvorexant (i) reduced the number of cocaine infusions earned during progressive
ratio self-administration; (ii) attenuated initial positive hedonic reactivity to
cocaine and prevented cocaine place preference; (iii) did not affect cocaine
induced hyperlocomotion and (iv) reduced cocaine-induced elevations in
extracellular ventral striatal dopamine. The present study examined the
therapeutic potential of suvorexant in rodent models of cocaine use disorder.
These results contribute toward a growing literature supporting therapeutic roles
of orexin receptor antagonists in treating substance use disorders.
PMID- 28419647
TI - A dramatic response to a single dose of infliximab in a patient with prolonged
pustular psoriasis derived from inverse psoriasis.
AB - We report a case of a 25-year-old Chinese man with an exceptionally prolonged
history of pustular psoriasis derived from inverse psoriasis who was unsatisfied
with conventional treatment and was successfully treated with a single dose of
infliximab without noticeable adverse effects. No recurrence or flaring was
observed after 3 months of follow-up. This case illustrates that infliximab may
be an effective and safe therapeutic option for patients with refractory pustular
psoriasis derived from inverse psoriasis.
PMID- 28419648
TI - The role of body image dissatisfaction in the association between treatment
related scarring or disfigurement and psychological distress in adult survivors
of childhood cancer.
AB - OBJECTIVE: To examine the potential mediating role of body image dissatisfaction
on the association between treatment-related scarring/disfigurement and
psychological distress in adult survivors of childhood cancer. METHODS:
Participants included 1714 adult survivors of childhood cancer (mean [SD] age at
evaluation = 32.4 [8.0] years, time since diagnosis = 24.1 [8.1] years) enrolled
in the St. Jude Lifetime Cohort Study. Survivors completed measures of body
image, emotional distress, and posttraumatic stress symptoms (PTSS). Body image
dissatisfaction (BID) was categorized into 2 groups (cancer-related and general)
based on factor analysis. Using causal mediation analysis, we estimated the
proportion of psychological distress associated with treatment-related
scarring/disfigurement that could be eliminated by resolving BID through a
hypothetical intervention. RESULTS: Among survivors with scarring/disfigurement
of the head, a sizable proportion of the relative excess of psychological
distress could be eliminated if BID was successfully treated (males: [cancer
related BID: depression: 63%; anxiety: 100%; PTSS: 52%]; [general BID:
depression: 70%; anxiety: 100%; PTSS: 42%]; females: [cancer-related BID:
depression: 20%; anxiety; 36%; PTSS: 23%]; [general BID: depression: 32%;
anxiety: 87%; PTSS: 38%]). The mediating effect of BID was less pronounced for
the association between scarring/disfigurement of the body and psychological
distress for both males and females. CONCLUSIONS: Body image dissatisfaction
mediates the association treatment-related scarring/disfigurement and
psychological distress among adult survivors of childhood cancer, particularly
among survivors with scarring/disfigurement of the head and male survivors.
Successful treatment of body image dissatisfaction has the potential to eliminate
a substantial proportion of psychological distress related to
scarring/disfigurement among adult survivors of childhood cancer.
PMID- 28419649
TI - A paradigm for examining stress effects on alcohol-motivated behaviors in
participants with alcohol use disorder.
AB - Although epidemiological research has shown an increase in drinking following
stressors and trauma, limited paradigms have been validated to study the
relationship between stress and drinking in the human laboratory. The current
study developed a progressive ratio (PR) operant procedure to examine the effects
of psychosocial stress on alcohol craving and several alcohol-motivated behaviors
in persons with alcohol use disorder. Current heavy, nontreatment-seeking
drinkers (N = 30) were media-recruited and completed a comprehensive assessment
of recent drinking, mood and health. Participants were admitted to the clinical
research unit and underwent 4-day, physician-monitored alcohol abstinence. On
days 4 and 5, participants underwent the Trier Social Stress Test or a neutral
session in random order followed by the alcohol-motivated response (AMR)
procedure in which subjects worked for money or alcohol under a PR operant
procedure. Subjects received earned money vouchers or alcohol at the conclusion
of the session. The Trier Social Stress Test increased alcohol craving and rate
of responding and decreased the number of changeovers between alcohol versus
money reinforcers on the PR schedule. There was a positive relationship between
alcohol craving and drinks earned during the stress session. This novel paradigm
provides an experimental platform to examine motivation to drink without
confounding by actual alcohol ingestion during the work session, thereby setting
the stage for future studies of alcohol interventions.
PMID- 28419651
TI - Reply Letter to "Does motor cortex plasticity depend on the type of mutation in
the LRRK2 gene?"
PMID- 28419650
TI - Cardiovascular safety in refractory incontinent patients with overactive bladder
receiving add-on mirabegron therapy to solifenacin (BESIDE).
AB - AIMS/OBJECTIVES: In the BESIDE study, combination therapy (antimuscarinic
[solifenacin] and beta3 -adrenoceptor agonist [mirabegron]) improved efficacy
over solifenacin monotherapy without exacerbating anticholinergic side effects in
overactive bladder (OAB) patients; however, a potential synergistic effect on the
cardiovascular (CV) system requires investigation. METHODS: OAB patients
remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind
run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5
mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg
for 12 weeks. CV safety assessments included frequency of CV-related treatment
emergent adverse events (TEAEs), change from baseline in vital signs (systolic
blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and
electrocardiogram (ECG) parameters. RESULTS: The frequency of hypertension,
tachycardia and ECG QT prolongation, respectively, was low and comparable across
combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and
solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from
baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination
(0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93
mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28
mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with
the exception of a mean treatment difference of ~1 mm Hg in SBP between
combination and solifenacin monotherapy; SBP was unchanged with combination and
decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG
parameters were generally similar across treatment groups, except for QT interval
corrected using Fridericia's formula, which was higher with solifenacin 10 mg
(3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77
mseconds). CONCLUSION: The comparable frequency of CV-related TEAEs, changes in
vital signs and ECG parameters indicates no synergistic effect on CV safety
outcomes when mirabegron and solifenacin are combined.
PMID- 28419652
TI - Degradation of an Ethylene Carbonate/Diethyl Carbonate Mixture by Using Ionizing
Radiation.
AB - The reactivity of ethylene carbonate (EC) and of a EC/diethyl carbonate (DEC)
mixture was studied under ionizing radiation to mimic the aging phenomena that
occur in lithium-ion batteries. Picosecond-pulse radiolysis experiments showed
that the attachment of the electron to the EC molecule is ultrafast (k(e-EC
+EC)=1.3*109 L mol-1 s-1 at 46 degrees C). This reaction rate is accelerated
by a factor of 5.7 compared with the electron attachment to propylene carbonate,
which implies that the presence of the methyl group significantly slows the
reaction. In a 50:50 EC/DEC mixture, just after the electron pulse the electron
is solvated by a mixture of EC and DEC molecules, but its fast decay is
attributed exclusively to electron attachment to the EC molecule. Stable products
detected after steady-state irradiation were mainly H2 , CH4 , CO, and CO2 . The
evolution of the radiolytic yields with the EC fraction shows that H2 and CH4 did
not exhibit linear behavior, whereas CO and CO2 did. Indeed, H2 and CH4 mainly
arise from the excited state of DEC, the formation of which is significantly
affected by the evolution of the dielectric constant of the mixture and by the
electron attachment to EC. CO formation is mainly due to the reactivity of the EC
molecule, which is not affected in the mixture, as proven by pulse-radiolysis
experiments.
PMID- 28419654
TI - Degradation and metabolism of synthetic plastics and associated products by
Pseudomonas sp.: capabilities and challenges.
AB - Synthetic plastics, which are widely present in materials of everyday use, are
ubiquitous and slowly-degrading polymers in environmental wastes. Of special
interest are the capabilities of microorganisms to accelerate their degradation.
Members of the metabolically diverse genus Pseudomonas are of particular interest
due to their capabilities to degrade and metabolize synthetic plastics.
Pseudomonas species isolated from environmental matrices have been identified to
degrade polyethylene, polypropylene, polyvinyl chloride, polystyrene,
polyurethane, polyethylene terephthalate, polyethylene succinate, polyethylene
glycol and polyvinyl alcohol at varying degrees of efficiency. Here, we present a
review of the current knowledge on the factors that control the ability of
Pseudomonas sp. to process these different plastic polymers and their by
products. These factors include cell surface attachment within biofilms,
catalytic enzymes involved in oxidation or hydrolysis of the plastic polymer,
metabolic pathways responsible for uptake and assimilation of plastic fragments
and chemical factors that are advantageous or inhibitory to the biodegradation
process. We also highlight future research directions required in order to
harness fully the capabilities of Pseudomonas sp. in bioremediation strategies
towards eliminating plastic wastes.
PMID- 28419653
TI - HCV viraemia associates with NK cell activation and dysfunction in antiretroviral
therapy-treated HIV/HCV-co-infected subjects.
AB - The impact of hepatitis C virus (HCV) RNA levels on immune status in chronically
HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy
(ART) remains poorly understood. A total of 78 African American subjects HCV
viraemic/naive to HCV treatment (33 HCV genotype 1 mono-infected, 45 ART-treated
HIV/HCV genotype 1 co-infected) were studied. Clinical and liver enzyme
measurements were performed. Whole blood was analysed for immune subset changes
by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used for same
day constitutive and in vitro Interferon (IFN)-alpha-induced signal transducer
and activator of transcription (STAT) phosphorylation, K562 target cell lysis and
K562 target cell recognition-mediated IFN-gamma production. Statistical analysis
was performed using R (2.5.1) or JMP Pro 11. While both groups did not differ in
the level of liver enzymes, HIV/HCV had higher T-cell activation/exhaustion, and
constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+ FoxP3+
CD25+ frequency, IFN-alphaR expression on NK cells, as well as constitutive and
IFN-alpha-induced direct cytotoxicity were lower in HIV/HCV. Linear regression
models further supported these results. Finally, increase in HCV viral load and
CD4+ T-cell count had an opposite effect between the two groups on NK cell
activity and T-cell activation, respectively. HCV viral load in ART-treated
HIV/HCV co-infection was associated with greater immune activation/exhaustion and
NK dysfunction than HCV viral load alone in HCV mono-infection. The more
pronounced immune modulation noted in ART-treated HIV-co-infected/untreated HCV
viraemic subjects may impact HCV disease progression and/or response to
immunotherapy.
PMID- 28419655
TI - Cytokine and adipokine are biofactors can act in blood and colostrum of obese
mothers.
AB - Breast milk contains bioactive components that contribute to newborn development.
However, colostrum may undergo biochemical and immunological changes as a
function of maternal overweight and obesity. To investigate this hypothesis, this
study determined the levels of hormones and immunological markers in the serum
and colostrum of overweight and obese mothers. Colostrum and serum samples were
collected from 15 normoweight, 15 overweight, and 15 obese women for
determination of leptin, adiponectin, cytokines (TNF-alpha, IL-6, IL-10), and C
reactive protein (CRP). Obese mothers exhibited higher levels of serum TNF-alpha,
IL-6, and CRP, serum and colostrum leptin and colostrum adiponectin and lower
levels of serum adiponectin. Leptin levels in maternal serum and colostrum were
positively correlated, as was pre-pregnancy BMI and serum TNF-alpha, IL-6, CRP,
and leptin. Adiponectin levels in colostrum and serum were negatively correlated.
The results suggest that obesity changes hormonal and immunological components of
maternal serum and colostrum. The modifications can have short-term and long-term
effects on newborn development. (c) 2016 BioFactors, 43(2):243-250, 2017.
PMID- 28419656
TI - Cannabis, psychosis and schizophrenia: unravelling a complex interaction.
AB - The relationship between cannabis and psychosis and schizophrenia has tested the
field of addiction for decades, and in some ways serves as measure of our ability
to provide a credible contribution to public health. As cannabis is used widely,
many people are interested in the risks the drug poses to mental health. This
paper focuses upon a seminal study examining this, the trajectory of subsequent
research findings and what this has meant for understanding and communicating
risk factor information. These studies provided evidence of a dose-response
relationship between cannabis and psychosis, and that for those individuals with
schizophrenia cannabis exacerbated their symptoms. The findings fit with a multi
causal model in which vulnerability interacts with a precipitating agent to
produce a disease outcome. Even though this is a common model in epidemiology, it
has proved difficult to communicate it in this case. This may be because at a
population level the increased risk is weak and the vulnerabilities relatively
rare. It may also be because people bring strongly held preconceptions to
interpreting a complex multi-causal phenomenon.
PMID- 28419657
TI - A new approach to clinical research: Integrating clinical care, quality
reporting, and research using a wound care network-based learning healthcare
system.
AB - The disparity between ideal evidence from randomized controlled trials and real
world evidence in medical research has prompted the United States Food and Drug
Administration to consider the use of real-world data to better understand safety
and effectiveness of new devices for a broader patient population and to
prioritize real-world data in regulatory decision making. As the healthcare
system transitions from volume- to value-based care, there is a growing need to
harness the power of real-world data to change the paradigm for wound care
clinical research and enable more generalizable clinical trials. This paper
describes the implementation of a network-based learning healthcare system by a
for-profit consortium of wound care clinics that integrates wound care
management, quality improvement, and comparative effectiveness research, by
harnessing structured real-world data within a purpose-built electronic health
record at the point of care. Centers participating in the consortium submit their
clinical data and quality measures to a qualified clinical data registry for
wound care, enabling benchmarking of their data across this national network. The
common definitional framework of the purpose-built electronic health record and
the 21 wound-specific quality measures help to standardize the potential sources
of bias in real-world data, making the consortium data useful for comparative
effectiveness research. This consortium can transform wound care clinical
research and raise the standards of care, while helping physicians achieve
success with the Merit-Based Incentive Payment System.
PMID- 28419658
TI - Ancestral Haloalkane Dehalogenases Show Robustness and Unique Substrate
Specificity.
AB - Ancestral sequence reconstruction (ASR) represents a powerful approach for
empirical testing structure-function relationships of diverse proteins. We
employed ASR to predict sequences of five ancestral haloalkane dehalogenases
(HLDs) from the HLD-II subfamily. Genes encoding the inferred ancestral sequences
were synthesized and expressed in Escherichia coli, and the resurrected ancestral
enzymes (AncHLD1-5) were experimentally characterized. Strikingly, the ancestral
HLDs exhibited significantly enhanced thermodynamic stability compared to extant
enzymes (DeltaTm up to 24 degrees C), as well as higher specific activities with
preference for short multi-substituted halogenated substrates. Moreover,
multivariate statistical analysis revealed a shift in the substrate specificity
profiles of AncHLD1 and AncHLD2. This is extremely difficult to achieve by
rational protein engineering. The study highlights that ASR is an efficient
approach for the development of novel biocatalysts and robust templates for
directed evolution.
PMID- 28419659
TI - Making visible the politics and ethics of alcohol policy research.
AB - Although research on alcohol policy has produced a huge international literature,
alcohol research and policy itself-its cultural assumptions, methods, politics
and ethics-has rarely been subject to critical analysis. In this article, I
provide an appreciative review of an exception to this trend: Joseph Gusfield's
1981 classic, The Culture of Public Problems: Drinking-Driving and the Symbolic
Order. I first outline Gusfield's argument that the 'problem of drinking-driving'
is constructed as a 'drama of individualism' centring on the 'killer drunk'. The
'culture' of drinking-driving research and policy emphasizes alcohol as the
problem and locates the source of car accidents in the moral failings of the
individual motorist, rather than in social institutions or physical environments.
For Gusfield, this construction of the problem is the outcome of political and
ethical choices rather than of 'objective' conditions. In the second part of the
article, I highlight the book's remarkable foresight in anticipating later trends
in critical policy analysis, and argue that it should be regarded as a
sociological classic and as required reading for those working in alcohol and
indeed other drug policy research. I conclude by arguing that The Culture of
Public Problems remains relevant to those working in alcohol and other drug
policy research, although the reasons for its relevance differ depending on
readers' theoretical commitments.
PMID- 28419660
TI - Acute masseter dystonia in a pediatric patient receiving aripiprazole and
methylphenidate following induction of general anesthesia.
AB - An 11-year-old male receiving aripiprazole, methylphenidate, and clonidine
developed acute masseter dystonia inhibiting tracheal intubation after induction
of general anesthesia with propofol and rocuronium. Following emergence, he had
trismus and jaw discomfort. Psychiatry consultation suspected an acute dystonic
reaction, so diphenhydramine was administered intravenously which resolved
symptoms. We suspect chronic aripiprazole and methylphenidate usage combined with
propofol administration in the short-term absence of methylphenidate made this
patient susceptible to dystonic reactions.
PMID- 28419661
TI - Cognitive behavioural therapy stabilises glycaemic control in adolescents with
type 1 diabetes-Outcomes from a randomised control trial.
AB - BACKGROUND: To compare the impact of cognitive behavioural therapy (CBT) with non
directive supportive counselling (NDC) on glycaemic control and psychological
well-being in adolescents with type 1 diabetes mellitus (T1DM). MATERIALS AND
METHODS: Participants aged 11 to 16 years with T1DM (duration >=1 year) from 4 UK
based paediatric diabetes centres were randomised to receive either 6 weekly
sessions of 1-to-1 CBT (n = 43) or NDC (n = 42), with 2 further sessions at 6 and
12 months. Follow-up continued for 12 months postintervention. Outcome measures
included glycated haemoglobin A1c (HbA1c) and psychological scores. RESULTS: The
HbA1c levels were available in 33 patients in each group for analysis. Between
group difference of the overall changes in HbA1c across the study period was
statically significant (P = .018). Geometric mean (range) HbA1c in the NDC group
deteriorated from 68 (46-113) to 78 (48-128) mmol/mol (ie, 8.4 [6.4-12.5]% to 9.3
[6.5-13.9]%; P = .001), but was maintained in the CBT group from 72 (46-129) to
73 (51-128) mmol/mol (P = .51) (ie, 8.7 [6.4-14]% to 8.9 [6.8-13.9]%). More
patients who have undergone CBT showed an improved or maintained HbA1c levels at
24 months (62.5% vs 35.5%, P = .032). Patients offered CBT with depressive scores
in the lowest tertile (least depressive symptoms) showed improvement in HbA1c
over time from 70 (46-102) to 67 (57-87) mmol/mol (P = .041) (ie, 8.6 [6.4-11.5]%
to 8.3 [7.4-10.1]%), but not in the NDC group. The CBT showed borderline
improvements in Children's Health Locus of Control (internal) scores over time
compared with NDC (P = .05). The self-efficacy score showed significant
improvement in both CBT (P < .001) and NDC (P = .03) groups over time.
CONCLUSIONS: CBT demonstrated better maintenance of glycaemic control compared
with NDC.
PMID- 28419662
TI - Ewing sarcoma of the sternal manubrium: first report of a case in Australasia and
review of the literature.
PMID- 28419663
TI - Total thyroidectomy for pressure symptoms in patients with Hashimoto's
thyroiditis.
AB - BACKGROUND: Hashimoto's thyroiditis (HT) is rarely on its own the indication for
thyroidectomy. However, surgery in patients with HT will be undertaken when there
is malignancy and may be required for pressure symptoms. Therefore, this study
aimed to investigate the indications for surgery in HT patients. METHODS: The
Monash University Endocrine Surgery Database was analysed from 1994 to 2013 for
patients with HT. Patients with HT were compared to a similar group of patients
with no HT on histopathology. Patient demographics, indication for surgery,
histopathology, gland weight and complications were analysed. RESULTS: A total of
2346 patients underwent total thyroidectomy during the study period. The median
age was 55 years. Eleven percent of patients had HT on final pathology
(259/2346). HT patients reported more pressure symptoms, 25.5% compared to those
with other pathology, 18.9% (P = 0.01). Patients with pressure symptoms had
heavier glands, 113 g compared to 85 g in those with other indications for
surgery (P = 0.048). Within the HT cohort, the median gland weight was 66 g
compared to 93 g in those without HT (P < 0.01). On multivariate analysis,
pressure symptoms as an indication for surgery was associated with HT (P < 0.01),
but age, gender and gland weight were not associated. In patients operated for
pressure with HT as the only pathology, 90% had relief of pressure symptoms.
CONCLUSION: Patients with HT were more likely to have pressure symptoms as an
indication for surgery independent of gland weights.
PMID- 28419664
TI - Effects of risk factors on periodontal disease defined by calibrated community
periodontal index and loss of attachment scores.
AB - OBJECTIVES: We evaluated whether and how the effects of risk factors on
periodontal disease (PD) were modified by measurement errors using community
periodontal index (CPI) and loss attachment (LA) in the community-based survey.
METHODS: A pilot validation study was performed to estimate the rates of false
negative and false positive for both CPI and LA in 31 subjects from different
regions using measurements from 12 well-trained dentists and a senior
periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was
conducted by enrolling 3,860 participants to estimate the effect of each risk
factor on PD calibrated with both sensitivity and specificity of two indices.
RESULTS: The values obtained for the sensitivity to false-positive ratio for CPI
ranged widely from 1.12 to 7.71, indicating regional variation in both errors.
The calibrated adjusted odds ratio for smoking vs non-smoking was higher than the
uncalibrated odds ratio for PD defined by CPI (2.75 (2.01, 3.77) vs 2.02 (1.63,
2.52)) and LA (3.85 (2.44, 6.13) vs 1.93 (1.47, 2.54)) scores. Similar
underestimation was noted for other risk factors. CONCLUSION: The effects of risk
factors on PD measured using CPI and LA in a large population-based survey were
underestimated without correcting for measurement errors.
PMID- 28419666
TI - Microbial ecology of mountain glacier ecosystems: biodiversity, ecological
connections and implications of a warming climate.
AB - Glacier ecosystems are teeming with life on, beneath, and to a lesser degree,
within their icy masses. This conclusion largely stems from polar research, with
less attention paid to mountain glaciers that overlap environmentally and
ecologically with their polar counterparts in some ways, but diverge in others.
One difference lies in the susceptibility of mountain glaciers to the near-term
threat of climate change, as they tend to be much smaller in both area and
volume. Moreover, mountain glaciers are typically steeper, more dependent upon
basal sliding for movement, and experience higher seasonal precipitation. Here,
we provide a modern synthesis of the microbial ecology of mountain glacier
ecosystems, and particularly those at low- to mid-latitudes. We focus on five
ecological zones: the supraglacial surface, englacial interior, subglacial
bedrock-ice interface, proglacial streams and glacier forefields. For each, we
discuss the role of microbiota in biogeochemical cycling and outline ecological
and hydrological connections among zones, underscoring the interconnected nature
of these ecosystems. Collectively, we highlight the need to: better document the
biodiversity and functional roles of mountain glacier microbiota; describe the
ecological implications of rapid glacial retreat under climate change and resolve
the relative contributions of ecological zones to broader ecosystem function.
PMID- 28419665
TI - Lettuce-produced hepatitis C virus E1E2 heterodimer triggers immune responses in
mice and antibody production after oral vaccination.
AB - The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases
(e.g. cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140
million people have chronic HCV infections and about 500 000 die yearly from HCV
related liver pathologies. To date, there is no licensed vaccine available to
prevent HCV infection and production of a HCV vaccine remains a major challenge.
Here, we report the successful production of the HCV E1E2 heterodimer, an
important vaccine candidate, in an edible crop (lettuce, Lactuca sativa) using
Agrobacterium-mediated transient expression technology. The wild-type dimer
(E1E2) and a variant without an N-glycosylation site in the E2 polypeptide
(E1E2?N6) were expressed, and appropriate N-glycosylation pattern and
functionality of the E1E2 dimers were demonstrated. The humoral immune response
induced by the HCV proteins was investigated in mice following oral
administration of lettuce antigens with or without previous intramuscular prime
with the mammalian HEK293T cell-expressed HCV dimer. Immunization by oral feeding
only resulted in development of weak serum levels of anti-HCV IgM for both
antigens; however, the E1E2?N6 proteins produced higher amounts of secretory IgA,
suggesting improved immunogenic properties of the N-glycosylation mutant. The
mice group receiving the intramuscular injection followed by two oral boosts with
the lettuce E1E2 dimer developed a systemic but also a mucosal immune response,
as demonstrated by the presence of anti-HCV secretory IgA in faeces extracts. In
summary, our study demonstrates the feasibility of producing complex viral
antigens in lettuce, using plant transient expression technology, with great
potential for future low-cost oral vaccine development.
PMID- 28419667
TI - Simple risk score for prediction of haemorrhagic complications after a
percutaneous renal biopsy.
AB - AIM: To derive a simple risk score to predict the individual risk of major
complications for patients undergoing a percutaneous renal biopsy procedure of
native kidneys. METHODS: The risk score was derived from a cohort of 1205 adult
patients subjected to percutaneous renal biopsy and assigned to training and
validation datasets. Factors associated with major complications were derived
from univariate analysis and then modelled by stepwise multivariate logistic
regression. Based on the odds ratio, independent predictors were assigned a
weighted integer. The risk score is calculated from the sum of the integers.
RESULTS: The overall incidence of major complications was 3.2%. Independent
factors associated with MC were lower pre-biopsy haemoglobin, lower platelets,
higher blood urea nitrogen, documented chronic kidney disease features in pre
biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A
score for pre-biopsy evaluation included the first four predictors and stratified
patients in three categories with increasing risk at higher scores (low-risk
0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good
discriminative power (AUC = 0.872). The addition of post-biopsy US findings
increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score
was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk
2.7%, high-risk 16.9%). CONCLUSION: The risk of major complications after a
percutaneous renal biopsy can be assessed by a simple risk score calculated from
readily available information.
PMID- 28419668
TI - Prevalence and associated variables of post-dialysis fatigue: Results of a
prospective multicentre study.
AB - AIM: The study aims to determine prevalence and severity of PDF and to define its
associated variables. METHODS: In five haemodialysis units of northern-centre
Italy, patients were regarded to suffer from PDF if they spontaneously offered
this complaint when asked the open-ended question: Do you feel better or worse
after dialysis? If worse, please specify in which way. A complaint of fatigue
would be probed further with questions directed at its duration, frequency and
intensity, allowing creation of a fatigue index of severity (one third of the sum
of these three parameters, each rated from 1 to 5). Patients were stratified into
three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3)
score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 did not. PDF
patients had significantly longer time of recovery after dialysis (TIRD). TIRD
was significantly associated with PDF duration, intensity, and frequency.
Patients with PDF were older and had a lower ADL score. At multivariate analysis,
PDF was significantly associated with TIRD. In a multivariate model that did not
include TIRD, PDF was independently associated with age and ADL. Sixty patients
had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and
dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the
ultrafiltration rate was lower. At multivariate analysis, PDF severity was
independently associated with TIRD. In the model without TIRD, PDF severity was
associated with ADL only. CONCLUSION: Post-dialysis fatigue is frequent and
associated with age and ADL. Dialytic variables seem unrelated to PDF.
PMID- 28419671
TI - Oral injuries in children presenting to a Japanese pediatric emergency room.
AB - BACKGROUND: Oral injuries are common among children, but studies on oral injury
according to the presence of foreign objects in the mouth are limited. The aim of
this study was to compare injury patterns and their effects in children
presenting to a Japanese pediatric emergency room (ER) with and without foreign
objects in the mouth. METHODS: Children who were brought to the ER at Tokyo
Metropolitan Children's Medical Center with oral injuries between 1 January 2011
and 31 December 2012, were included. Information regarding mechanism of injury,
object related to injury, required procedure, and disposition (i.e. placement
after ER evaluation: hospitalization or discharge) was collected. Injured
subjects with and without foreign objects in the mouth were compared. RESULTS:
Three hundred and nineteen subjects were included in analysis. Median age was 26
months. Labial mucosa, tongue, buccal mucosa, and teeth were major locations of
injury. Tumble (i.e. fall from standing) was the leading mechanism of injury
(50%). Seventy-one subjects (22%) were holding foreign objects in the mouth when
injury occurred. A toothbrush was the most common object (31%). Subjects with
foreign objects in the mouth were more likely to injure the posterior parts of
the mouth, and to require imaging (P = 0.04) and hospital admission (P < 0.001).
This was also the case for children with injury due to tumble. CONCLUSIONS:
Tumble (i.e. fall from standing) was the most common mechanism of injury.
Furthermore, requirement for medical resources increased if children had foreign
objects in their mouth. Preventive measures should focus on educating parents
about the dangers associated with children moving around while holding objects in
the mouth.
PMID- 28419670
TI - Sodium-glucose co-transporter (SGLT)2 and SGLT1 renal expression in patients with
type 2 diabetes.
AB - AIM: To quantify the expression of sodium-glucose co-transporter (SGLT)2 and
SGLT1, their cognate basolateral transporters, GLUT2 and GLUT1, and the
transcriptional regulator of SGLTs in renal tissue obtained from people with T2DM
and a group of well-matched people without diabetes. METHODS: We measured SGLT2
and SGLT1 expression in unaffected renal tissue from 19 people with T2DM and 20
people without diabetes, matched for age and estimated glomerular filtration rate
(controls), undergoing unilateral nephrectomy. Expression of SGLT2 and SGLT1, as
well as that of GLUT2 and GLUT1, was quantified using real-time and digital PCR;
an affinity-purified antibody against human SGLT2 was used to localize SGLT2 by
immunohistochemistry. RESULTS: SGLT2 expression was higher in control than T2DM
tissue (median [interquartile range] target/beta-actin 1.62 [2.02] vs 0.67
[0.61]; P < .0001), and SGLT1 trended in the same direction (0.98 [1.19] vs 0.44
[0.48]; P = .08). Immunohistochemistry clearly localized SGLT2 to the tubular
brush-border membranes, and was semi-quantitatively stronger in control than T2DM
tissue (5.0 [1.0] vs 4.0 [1.0] score units; P = .043). GLUT2 (control vs T2DM:
1.00 [0.69] vs 0.49 [0.36]) and GLUT1 expression (control vs T2DM: 0.86 [0.73] vs
0.35 [0.30]; P = .0007 for both) were closely correlated with those of the
respective SGLT partner. Hypoxia-inducible factor 1alpha, more abundant in
control than T2DM tissue, might be a transcription factor involved in the
modulation of SGLT2 expression. CONCLUSIONS: In whole renal tissue, expressions
of SGLT2/GLUT2 and SGLT1/GLUT1 are coupled and slightly lower in typical people
with T2DM as compared with well-matched people without diabetes.
PMID- 28419672
TI - Laparoscopic ventral mesh rectopexy - a video vignette.
PMID- 28419673
TI - Total mesorectal excision with Denonvilliers' fascia in anterior rectal tumours
using taTME technique - a video vignette.
PMID- 28419674
TI - Prognostic risk factors of first recurrence in patients with primary stages I-II
cutaneous malignant melanoma - from the population-based Swedish melanoma
register.
AB - BACKGROUND: Prognostic factors in patients with localized primary cutaneous
malignant melanoma (CMM) are well described. However, prognostic factors for
recurrence are less documented. OBJECTIVES: The aim of this study was to identify
prognostic risk factors for first recurrence in patients with localized stages I
II CMM using population-based data. METHODS: This study included 1437 CMM
patients registered in one region of Sweden during 1999-2012 follow-up through 31
December 2012. To identify first recurrence of CMM disease, data from a care data
warehouse, the pathology and radiology department registries were used. Patients
were also followed through a census register and the national Cause of Death
Register. RESULTS: The 5- and 10-year recurrence-free survival (RFS) were 85.7%
and 81.2%, respectively. The most common site of first recurrence was regional
lymph node metastasis closely followed by distant metastasis. After adjusting for
all prognostic factors, women had 50% lower risk of recurrence than men (HR =
0.5, 95% CI 0.4-0.7) and patients >=70 had higher risk compared to patients 55-69
years (HR = 1.7, 95% CI 1.2-2.5). Other significant prognostic factors for risk
of recurrence were tumour thickness, presence of ulceration, Clark's level of
invasion and histogenetic type. CONCLUSION: Tumour thickness was found to be the
predominant risk factor for recurrence. The prognostic factors for recurrence
coincided with prognostic factors for CMM death. The most common site of first
recurrence in stages I-II CMM is regional lymph node (42.8%) closely followed by
distant metastases (37.6%), a fact which has to be taken into consideration when
choosing follow-up strategies.
PMID- 28419675
TI - Melanin for space travel radioprotection.
PMID- 28419676
TI - Efficacy of dacarbazine as a rescue agent for histiocytic sarcoma in dogs.
AB - BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive neoplasm that is
generally associated with a poor prognosis. CCNU is considered first-line medical
therapy, although the majority of dogs ultimately develop progressive disease.
The objective of this study was to evaluate the efficacy of dacarbazine as a
rescue agent for HS. MATERIALS AND METHODS: Medical records of dogs diagnosed
with HS that received at least one dose of dacarbazine were reviewed. Information
collected and analyzed included signalment, disease distribution, treatment
history, dacarbazine treatments (including dose, interval and total number of
cycles), adverse events, and response to treatment. RESULTS: Seventeen dogs were
included, all of which had disseminated or metastatic disease and had received
prior treatment with CCNU. Three dogs achieved partial remission for an overall
response rate of 17.6%. The overall median event-free survival (EFS) was 21 days.
For dogs that experienced an objective response, the EFS was 70 days. Toxicity
secondary to dacarbazine was generally mild and self-limiting. CONCLUSION: In the
setting of advanced disease, dacarbazine appears to have modest activity against
HS and warrants further investigation.
PMID- 28419677
TI - Transanal minimally invasive surgery for excision of rectal carcinoid - a video
vignette.
PMID- 28419678
TI - Secondary compounds from exotic tree plantations change female mating preferences
in the palmate newt (Lissotriton helveticus).
AB - Selection can favour phenotypic plasticity in mate choice in response to
environmental factors that alter the costs and benefits of being choosy, or of
choosing specific mates. Human-induced environmental change could alter sexual
selection by affecting the costs of mate choice, or by impairing the ability of
individuals to identify preferred mates. For example, variation in mate choice
could be driven by environmentally induced differences in body condition (e.g.
health) that change the cost of choosiness, or by environmental effects on the
ability to detect or discriminate sexual signals. We teased apart these
possibilities experimentally, by comparing female mate choice in the palmate newt
Lissotriton helveticus between environments that mimic water from either native
oak forests or exotic eucalypt plantations. In laboratory two-choice mate trials
in clean water, females with prolonged exposure (21 days) to waterborne chemicals
leached from eucalypt leaves did not preferentially associate with the male with
a stronger immune response, but females exposed to water with chemicals from oak
leaves did. In contrast, female choice was unaffected by the immediate presence
or absence of eucalypt leachates during mate choice (using only females
previously held in oak-treated water). The habitat-related change in female
choice we observed is likely to be driven by effects of eucalypt leachates on
female physiology, rather than immediate inhibition of pheromone transmission or
blocking of pheromone reception.
PMID- 28419679
TI - Assessing the survival impact of perioperative opioid consumption in children and
adolescents undergoing cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy.
AB - BACKGROUND: Several studies in adult patients have suggested an unfavorable
association between opioid consumption and cancer progression. AIMS: This study
investigated the impact of opioid consumption on the survival of children and
adolescents undergoing cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy. METHODS: A retrospective study of patients <19 years who had
undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
was performed. Univariate and multivariate Cox proportional hazard analyses were
used to identify factors associated with recurrence-free survival and overall
survival. RESULTS: Seventy-five patients were identified. Median age was 11.6
years (range, 1.8-18.9), and 43% was female. Median perioperative opioid
consumption was 18.9 morphine dose equivalents per kilogram (range, 0.6-339.6).
There was no statistically significant association between opioid consumption and
recurrence-free survival [hazard ratio, 1.00; 95% confidence interval, (0.99
1.02), P = 0.55] or overall survival [hazard ratio 1.01; 95% confidence interval
(0.99-1.03), P = 0.22]. Independent prognostic factors associated with poor
survival included incomplete cytoreduction and extra-abdominal disease.
CONCLUSION: In this retrospective study of children and adolescents who had
undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy,
there was no statistically significant association between opioid consumption and
recurrence-free survival or overall survival.
PMID- 28419680
TI - BOLD neurovascular coupling does not change significantly with normal aging.
AB - Studies of cognitive function that compare the blood oxygenation level dependent
(BOLD) signal across age groups often require the assumption that neurovascular
coupling does not change with age. Tests of this assumption have produced mixed
results regarding the strength of the coupling and its relative time course.
Using deconvolution, we found that age does not have a significant effect on the
time course of the hemodynamic impulse response function or on the slope of the
BOLD versus stimulus duration relationship. These results suggest that in
cognitive studies of healthy aging, group differences in BOLD activation are
likely due to age-related changes in cognitive-neural interactions and
information processing rather than to impairments in neurovascular coupling. Hum
Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419681
TI - Oral mycobiome in community-dwelling elderly and its relation to oral and general
health conditions.
AB - OBJECTIVE: Oral fungal infection is generally associated with dysbiosis related
to antibiotic use, immunodeficiency, or frailty. However, fungal colonization in
a typical population without apparent symptoms and its associated conditions are
poorly understood. In this study, oral fungal colonization in community-dwelling
and independently living elderly populations was evaluated and factors affecting
fungal colonization were analyzed. SUBJECTS AND METHODS: The subjects (410; 181
males and 229 females) were 75-99 years of age; those under prior antibiotic use
were excluded. Fungal populations in the saliva were evaluated by PCR-based
molecular techniques. Body mass index (BMI), smoking habits, and oral health
conditions were examined. RESULTS: Salivary fungal amounts exceeded 104 CFU/ml
in 63 (15.4%) of 410 subjects. Candida albicans was most frequently detected
(98.4%), followed by Candida glabrata (54.0%), and Candida dubliniensis (38.1%)
in those subjects with fungi at 104 CFU/ml or over. Fungi at 104 CFU/ml or over
in the presence of C. glabrata or C. dubliniensis was significantly associated
with low BMI. CONCLUSIONS: Candida albicans, C. glabrata, and C. dubliniensis
dominated the oral mycobiome in Japanese community-dwelling elderly. Lower BMI
might signify compromised health status and thus could result in susceptibility
to specific candidiasis by C. glabrata and C. dubliniensis.
PMID- 28419682
TI - Game theoretical mapping of causal interactions underlying visuo-spatial
attention in the human brain based on stroke lesions.
AB - Anatomical studies conducted in neurological conditions have developed our
understanding of the causal relationships between brain lesions and their
clinical consequences. The analysis of lesion patterns extended across brain
networks has been particularly useful in offering new insights on brain-behavior
relationships. Here we applied multiperturbation Shapley value Analysis (MSA), a
multivariate method based on coalitional game theory inferring causal regional
contributions to specific behavioral outcomes from the characteristic functional
deficits after stroke lesions. We established the causal patterns of
contributions and interactions of nodes of the attentional orienting network on
the basis of lesion and behavioral data from 25 right hemisphere stroke patients
tested in visuo-spatial attention tasks. We calculated the percentage of damaged
voxels for five right hemisphere cortical regions contributing to attentional
orienting, involving seven specific Brodmann Areas (BA): Frontal Eye Fields, (FEF
BA6), Intraparietal Sulcus (IPS-BA7), Inferior Frontal Gyrus (IFG-BA44/BA45),
Temporo-Parietal Junction (TPJ-BA39/BA40), and Inferior Occipital Gyrus (IOG
BA19). We computed the MSA contributions of these seven BAs to three behavioral
clinical tests (line bisection, bells cancellation, and letter cancelation). Our
analyses indicated IPS as the main contributor to the attentional orienting and
also revealed synergistic influences among IPS, TPJ, and IOG (for bells
cancellation and line bisection) and between TPJ and IFG (for bells and letter
cancellation tasks). The findings demonstrate the ability of the MSA approach to
infer plausible causal contributions of relevant right hemisphere sites in
poststroke visuo-spatial attention and awareness disorders. Hum Brain Mapp, 2017.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28419684
TI - Should organs from hepatitis C virus-infected donors be used for transplantation
in the era of DAAs?
PMID- 28419685
TI - Scaffolds for epithelial tissue engineering customized in elastomeric molds.
AB - Restoration of soft tissue defects remains a challenge for surgical
reconstruction. In this study, we introduce a new approach to fabricate poly(d,l
lactic acid) (PDLLA) scaffolds with anatomical shapes customized to regenerate
three-dimensional soft tissue defects. Highly concentrated polymer/salt mixtures
were molded in flexible polyether molds. Microcomputed tomography showed that
with this approach it was possible to produce scaffolds with clinically
acceptable volume ratio maintenance (>90%). Moreover, this technique allowed us
to customize the average pore size and pore interconnectivity of the scaffolds by
using variations of salt particle size. In addition, this study demonstrated that
with the increasing porosity and/or the decreasing of the average pore size of
the PDLLA scaffolds, their mechanical properties decrease and they degrade more
slowly. Cell culture results showed that PDLLA scaffolds with an average pore
size of 100 um enhance the viability and proliferation rates of human gingival
epithelial cells up to 21 days. The simple method proposed in this article can be
extended to fabricate porous scaffolds with customizable anatomical shapes and
optimal pore structure for epithelial tissue engineering. (c) 2017 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 880-890, 2018.
PMID- 28419683
TI - Geographical differences in survival of dogs with non-Hodgkin lymphoma treated
with a CHOP based chemotherapy protocol.
AB - BACKGROUND: In humans geographical differences in the incidence and presentation
of various cancers have been reported. However, much of this information has not
been collected in veterinary oncology. AIM: The purpose of this study was to
determine if a geographic difference in progression free survival exists for dogs
with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of
775 cases of canine lymphoma from 3 US regions (west, south and north), treated
with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from
referral institutions and were required to have received at least one doxorubicin
treatment and have follow up information regarding time to progression. RESULTS:
Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001),
immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were
seen between regions. Upon univariate analysis, progression free survival (PFS)
differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and
immunophenotype (p = 0.001). A multivariable Cox regression model showed that
dogs in the western region had a significantly shorter PFS when compared to the
south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage
and phenotype.
PMID- 28419686
TI - Gastrointestinal mucormycosis in an immunocompromised host.
PMID- 28419687
TI - Skeletal muscle analyses: agreement between non-contrast and contrast CT scan
measurements of skeletal muscle area and mean muscle attenuation.
AB - Low skeletal muscle area (SMA) and muscle radiation attenuation (MRA) have been
associated with poor prognosis in various patient populations. Both non-contrast
and contrast CT scans are used to determine SMA and MRA. The effect of the use of
a contrast agent on SMA and MRA is unknown. Therefore, we investigated agreement
between these two scan options. SMA and MRA of 41 healthy individuals were
analysed on a paired non-contrast and contrast single CT scan, and agreement
between paired scan results was assessed with use of Bland-Altman plots,
intraclass correlation coefficients (ICCs), standard error of measurements (SEM)
and smallest detectable differences at a 95% confidence level (SDD95 ). Analyses
were stratified by tube voltage. Difference in SMA between non-contrast and
contrast scans made with a different tube voltage was 7.0 +/- 7.5 cm2 ; for scans
made with the same tube voltage this was 2.3 +/- 1.7 cm2 . Agreement was
excellent for both methods: ICC: 0.952, SEM: 7.2 cm2 , SDD95 : 19.9 cm2 and ICC:
0.997, SEM: 2.0 cm2 , SDD95 : 5.6 cm2 , respectively. MRA of scans made with a
different tube voltage differed 1.3 +/- 11.3 HU, and agreement was poor (ICC:
0.207, SEM: 7.9 HU, SDD95 : 21.8 HU). For scans made with the same tube voltage
the difference was 6.7 +/- 3.2 HU, and agreement was good (ICC: 0.682, SEM: 5.3
HU, SDD95 : 14.6 HU). In conclusion, SMA and MRA can be slightly influenced by
the use of contrast agent. To minimise measurement error, image acquisition
parameters of the scans should be similar.
PMID- 28419688
TI - Combined laparoscopic-robotic approach in complex re-operative colorectal surgery
- a video vignette.
PMID- 28419689
TI - Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in
human FARS2.
AB - Mutations in the mitochondrial aminoacyl-tRNA synthetases (mtaaRSs) can cause
profound clinical presentations, and have manifested as diseases with very
selective tissue specificity. To date most of the mtaaRS mutations could be
phenotypically recognized, such that clinicians could identify the affected
mtaaRS from the symptoms alone. Among the recently reported pathogenic variants
are point mutations in FARS2 gene, encoding the human mitochondrial PheRS.
Patient symptoms range from spastic paraplegia to fatal infantile Alpers
encephalopathy. How clinical manifestations of these mutations relate to the
changes in three-dimensional structures and kinetic characteristics remains
unclear, although impaired aminoacylation has been proposed as possible etiology
of diseases. Here, we report four crystal structures of HsmtPheRS mutants, and
extensive MD simulations for wild-type and nine mutants to reveal the structural
changes on dynamic trajectories of HsmtPheRS. Using steady-state kinetic
measurements of phenylalanine activation and tRNAPhe aminoacylation, we gained
insight into the structural and kinetic effects of mitochondrial disease-related
mutations in FARS2 gene.
PMID- 28419691
TI - The low diverse gastric microbiome of the jellyfish Cotylorhiza tuberculata is
dominated by four novel taxa.
AB - Cotylorhiza tuberculata is an important scyphozoan jellyfish producing population
blooms in the Mediterranean probably due to pelagic ecosystem's decay. Its
gastric cavity can serve as a simple model of microbial-animal digestive
associations, yet poorly characterized. Using state-of-the-art metagenomic
population binning and catalyzed reporter deposition fluorescence in situ
hybridization (CARD-FISH), we show that only four novel clonal phylotypes were
consistently associated with multiple jellyfish adults. Two affiliated close to
Spiroplasma and Mycoplasma genera, one to chlamydial 'Candidatus Syngnamydia',
and one to bacteroidetal Tenacibaculum, and were at least one order of magnitude
more abundant than any other bacteria detected. Metabolic modelling predicted an
aerobic heterotrophic lifestyle for the chlamydia, which were found
intracellularly in Onychodromopsis-like ciliates. The Spiroplasma-like organism
was predicted to be an anaerobic fermenter associated to some jellyfish cells,
whereas the Tenacibaculum-like as free-living aerobic heterotroph, densely
colonizing the mesogleal axis inside the gastric filaments. The association
between the jellyfish and its reduced microbiome was close and temporally stable,
and possibly related to food digestion and protection from pathogens. Based on
the genomic and microscopic data, we propose three candidate taxa: 'Candidatus
Syngnamydia medusae', 'Candidatus Medusoplasma mediterranei' and 'Candidatus
Tenacibaculum medusae'.
PMID- 28419692
TI - Associating Liver Partition and Portal vein ligation for Staged hepatectomy after
pre-operative chemotherapy.
AB - BACKGROUND: Recently a procedure termed 'Associating Liver Partition and Portal
vein ligation for Staged hepatectomy' (ALPPS) was developed to increase the
resectability of marginally resectable or locally unresectable liver tumours.
This study focused on the application of ALPPS in patients with advanced
colorectal liver metastases (CRLM) and pre-operative chemotherapy, with the aim
to investigate whether the latter still allows for sufficient hypertrophy of the
future liver remnant (FLR) following the first step of ALPPS. METHODS:
Retrospective analysis was performed on six patients suffering from advanced
CRLM. Analyses comprised demographical and basic clinical data, the perioperative
courses as well as short- and long-term outcomes. RESULTS: All patients presented
with bilobular CRLM and pre-operative chemotherapy of at least 6 months. Extended
right hemihepatectomy was performed in all cases, four patients additionally
received atypical resections in segments II/III. Mean FLR prior to step 1 of
ALPPS was 397.9 cm3 (121-753 cm3 ), on average representing 20.9% of the total
liver volume (13.2-27.1%). A mean hypertrophy of the FLR of 67.9% (32.5-94.1%)
was achieved. Overall, severe morbidity (Dindo Clavien >3a) occurred in two
patients. Following completion of ALPPS, mean post-operative disease-free
survival was 5.7 months (2.6-8.9 months). CONCLUSION: Despite pre-operative
chemotherapy, ALPPS seems to result in adequate liver hypertrophy, preventing
post-operative small-for-size syndrome. However, there might be a high risk of
tumour recurrence in patients with an aggressive tumour biology.
PMID- 28419693
TI - Ag-loaded MgSrFe-layered double hydroxide/chitosan composite scaffold with
enhanced osteogenic and antibacterial property for bone engineering tissue.
AB - Bone tissue engineering scaffolds for the reconstruction of large bone defects
should simultaneously promote osteogenic differentiation and avoid postoperative
infection. Herein, we develop, for the first time, Ag-loaded MgSrFe-layered
double hydroxide/chitosan (Ag-MgSrFe/CS) composite scaffold. This scaffold
exhibits three-dimensional interconnected macroporous structure with a pore size
of 100-300 MUm. The layered double hydroxide nanoplates in the Ag-MgSrFe/CS show
lateral sizes of 200-400 nm and thicknesses of ~50 nm, and the Ag nanoparticles
with particle sizes of ~20 nm are uniformly dispersed on the scaffold surfaces.
Human bone marrow-derived mesenchymal stem cells (hBMSCs) present good adhesion,
spreading, and proliferation on the Ag-MgSrFe/CS composite scaffold, suggesting
that the Ag and Sr elements in the composite scaffold have no toxicity to hBMSCs.
When compared with MgFe/CS composite scaffold, the Ag-MgSrFe/CS composite
scaffold has better osteogenic property. The released Sr2+ ions from the
composite scaffold enhance the alkaline phosphatase activity of hBMSCs, promote
the extracellular matrix mineralization, and increase the expression levels of
osteogenic-related RUNX2 and BMP-2. Moreover, the Ag-MgSrFe/CS composite scaffold
possesses good antibacterial property because the Ag nanoparticles in the
composite scaffold effectively prevent biofilm formation against S. aureus.
Hence, the Ag-MgSrFe/CS composite scaffold with excellent osteoinductivity and
antibacterial property has a great potential for bone tissue engineering. (c)
2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 863
873, 2018.
PMID- 28419694
TI - Quantitative depth resolved microcirculation imaging with optical coherence
tomography angiography (Part IotaIota): Microvascular network imaging.
AB - In this work, we review the main phenomena that have been explored in OCT
angiography to image the vessels of the microcirculation within living tissues
with the emphasis on how the different processing algorithms were derived to
circumvent specific limitations. Parameters are then discussed that can
quantitatively describe the depth-resolved microvascular network for possible
clinic diagnosis applications. Finally,future directions in continuing OCT
development are discussed. This article is protected by copyright. All rights
reserved.
PMID- 28419695
TI - Flavivirus cross-reactivity, Guillain-Barre syndrome, and hematopoietic stem cell
transplant patient: A comment.
PMID- 28419696
TI - Risk Factors Associated with Pain on Chronic Intermittent Hemodialysis: A
Systematic Review.
AB - OBJECTIVES: The aim of the study was to define risk factors related to pain in
adult end-stage renal disease (ESRD) patients on chronic intermittent
hemodialysis (HD) by developing a systematic review of published data. METHODS:
The search was conducted from MEDLINE, Scopus, PsycINFO, and the Cumulative Index
to Nursing and Allied Health Literature (CINAHL). Manuscripts in all languages
were considered. Two authors performed each step independently, and all
disagreements were resolved after discussion with the third author. Quality of
studies was analyzed using the Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) checklist and Cochrane risk of bias tool.
RESULTS: A total of 67 studies with 7,818 participants were included (median
number of participants = 60). Most of the studies reported common factors such as
age, gender, body mass index, race/ethnicity, marital status, duration of HD
treatment since initiation of HD, different comorbidities, and biochemical
parameters. Other studies reported more specific factors such as type, regimen or
place of hemodialysis, type of dialyzer, dialysis phase, type of dialyzer
membrane, administration site, type of preparation, and dose of erythropoiesis
stimulating agent (ESA). The studies indicate that these factors may contribute
to increased pain in general and also promote development of different pain
modalities of various locations and causes in HD patients (eg, pain in general,
pain related to arteriovenous access, headache, musculoskeletal pain, ESA
application pain). DISCUSSION: Multiple factors for various types of pain in very
heterogeneous populations and heterogeneous settings were analyzed in the
literature. The results turned out to be inconsistent between the studies. Future
large-scale studies are required, taking into the account limitations of the
current evidence base.
PMID- 28419697
TI - Defensive High-Anxious Individuals Demonstrate Difference Responses to Pain
Management to Those with Lower Levels of Defensiveness and Anxiety.
AB - OBJECTIVES: Few studies have considered the effect of Weinberger et al.'s
personality types on the management of pain. The aims of this study were to (1)
identify whether the relationships between pain intensity, cognitive factors, and
disability at 3 and 6 months postbaseline differ as a result of personality type;
and (2) identify whether personality type affects the likelihood of achieving a
minimal clinically important change in pain intensity or disability at 3 and 6
months. METHOD: Patients completed a set of validated questionnaires assessing
personality type, cognitive factors, pain intensity, and disability at 3 and 6
months postbaseline. RESULTS: A greater proportion of defensive high-anxious
individuals reported improvement for both pain (3 months = 25%; 6 months = 38%)
and disability (3 months = 35%; 6 months = 50%) and showed stronger links between
improvements in pain and disability and baseline psychological factors than
nonextreme individuals. CONCLUSIONS: The high proportion of defensive high
anxious individuals highlights the need for psychologically based interventions
to be delivered earlier in the care process. Stratifying the population, based on
personality type, may allow for more targeted interventions, which could be more
cost effective and reduce the number of patients remaining in the care system.
PMID- 28419698
TI - Collagen barrier membranes do not adsorb hypoxia mimetic activity-Activity of
gingival fibroblasts cultured directly on collagen barrier membranes loaded with
hypoxia mimetic agents.
AB - Hypoxia-based strategies for applications in oral surgery and periodontology have
been proposed where collagen barrier membranes (CBM) are loaded with hypoxia
mimetic agents (HMA) to induce a pro-angiogenic response. While it was found that
CBM release HMA, it remained unclear if CBM adsorb HMA activity. Here we
evaluated the response of oral cells cultured on CBM, supplemented with the HMA
dimethyloxalylglycine (DMOG), desferrioxamine (DFO), and l-mimosine (l-MIM).
Gingival fibroblasts (GF) were cultured on unwashed CBM as well as on CBM that
had been washed with serum-free medium for 48 hours. The pro-angiogenic response
was measured based on vascular endothelial growth factor (VEGF) production.
Viability and proliferation were assessed based on MTT and BrdU assays. We found
that GF seeded onto CBM loaded with DFO and l-MIM, but not DMOG, showed an
increase in VEGF to 6.1-fold and 7.7-fold compared to unloaded CBM, respectively.
Cells remained vital, but a trend for decreased proliferation was observed on
DMOG and DFO-loaded CBM which did not reach the level of significance. Evaluation
of washed CBM revealed no difference between the unloaded CBM and CBM
supplemented with DMOG, DFO, or l-MIM. In conclusion, our results suggest that
CBM do not adsorb hypoxia mimetic activity but release HMA within the first
hours. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
106B: 874-879, 2018.
PMID- 28419699
TI - Cystic mesenteric lymphangioma: a case report.
PMID- 28419700
TI - Pregnancy Ambivalence and Long-Acting Reversible Contraceptive (LARC) Use Among
Young Adult Women: A Qualitative Study.
AB - CONTEXT: Many young adults are unclear about how much they want to have, or
prevent having, a baby. However, pregnancy ambivalence is an underexamined factor
in the uptake of long-acting reversible contraceptive (LARC) methods-IUDs and
implants-the most effective methods available. METHODS: In 2014, investigators
conducted six focus groups and 12 interviews with 50 women aged 18-29 in Dane
County, Wisconsin; participants were either university students or community
residents receiving public assistance. A modified grounded theory approach was
used to analyze the data. RESULTS: Four themes emerged. First, participants
described a pregnancy desire spectrum: Those strongly motivated to avoid
pregnancy were most receptive to LARC methods, while those with less clear or
mixed desires worried that these methods would prevent "accidental" pregnancies
that might not be unwelcome. Second, women within a few years of wanting children
perceived LARC methods as too "permanent," despite awareness of their
reversibility. Third, age and life stage were important factors: Younger women
and those attending school or beginning careers were more likely than others to
consider these methods because they had clearer motivations to avoid pregnancy.
Finally, relationship stage influenced receptiveness to LARC methods: Women in
newer relationships were more receptive than were those in longer term
relationships who imagined having a baby with their partner someday. CONCLUSION:
Effectiveness is not the only factor in women's selection and use of
contraceptive methods. Individual preferences will lead some women to choose non
LARC methods even when fully informed of their options.
PMID- 28419701
TI - OMIP-038: Innate immune assessment with a 14 color flow cytometry panel.
PMID- 28419702
TI - Evaluation of the truebeam machine performance check (MPC): mechanical and
collimation checks.
AB - Machine performance check (MPC) is an automated and integrated image-based tool
for verification of beam and geometric performance of the TrueBeam linac. The
aims of the study were to evaluate the performance of the MPC geometric tests
relevant to beam collimation (MLC and jaws) and mechanical systems (gantry and
collimator). Evaluation was performed by comparing MPC to QA tests performed
routinely in the department over a 4-month period. The MPC MLC tests were
compared to an in-house analysis of the Picket Fence test. The jaw positions were
compared against an in-house EPID-based method, against the traditional light
field and graph paper technique and against the Daily QA3 device. The MPC
collimator and gantry were compared against spirit level and the collimator
further compared to Picket Fence analysis. In all cases, the results from the
routine QA procedure were presented in a form directly comparable to MPC to allow
a like-to-like comparison. The sensitivity of MPC was also tested by deliberately
miscalibrating the appropriate linac parameter. The MPC MLC was found to agree
with Picket Fence to within 0.3 mm and the MPC jaw check agreed with in-house
EPID measurements within 0.2 mm. All MPC parameters were found to be accurately
sensitive to deliberately introduced calibration errors. For the tests evaluated,
MPC appears to be suitable as a daily QA check device.
PMID- 28419703
TI - Exercise capacity following pediatric heart transplantation: A systematic review.
AB - Pediatric HTs account for 13% of all HTs with >60% of recipients surviving at
least 10 years post-HT. The purpose of this systematic review is to synthesize
the literature on exercise capacity of pediatric HT recipients to improve
understanding of the mechanisms that may explain the decreased exercise capacity.
Six databases were searched for studies that compared the exercise capacity of HT
recipients <=21 years old with a control group or normative data. Sixteen studies
were included. Pediatric HT recipients, as compared to controls or normative
data, exhibit significantly higher resting HR, and at peak exercise exhibit
significantly decreased HR, VO2 , power, work, minute ventilation, and exercise
duration. Peak VO2 appears to improve within the first 2.5 years post-HT; peak
work remains constant; and there is inconclusive evidence that peak HR, HR
recovery, and HR reserve improve with time since HT. These results are discussed
in the context of the mechanisms that may explain the impaired exercise capacity
of pediatric HT recipients, including chronotropic incompetence, graft
dysfunction, side effects of immunosuppression therapy, and deconditioning. In
addition, the limited literature on rehabilitation after pediatric HT is
summarized.
PMID- 28419704
TI - Robustness of a model microbial community emerges from population structure among
single cells of a clonal population.
AB - Microbial populations can withstand, overcome and persist in the face of
environmental fluctuation. Previously, we demonstrated how conditional gene
regulation in a fluctuating environment drives dilution of condition-specific
transcripts, causing a population of Desulfovibrio vulgaris Hildenborough (DvH)
to collapse after repeatedly transitioning from sulfate respiration to syntrophic
conditions with the methanogen Methanococcus maripaludis. Failure of the DvH to
successfully transition contributed to the collapse of this model community. We
investigated the mechanistic basis for loss of robustness by examining whether
conditional gene regulation altered heterogeneity in gene expression across
individual DvH cells. We discovered that robustness of a microbial population
across environmental transitions was attributable to the retention of cells in
two states that exhibited different condition-specific gene expression patterns.
In our experiments, a population with disrupted conditional regulation
successfully alternated between cell states. Meanwhile, a population with intact
conditional regulation successfully switched between cell states initially, but
collapsed after repeated transitions, possibly due to the high energy
requirements of regulation. These results demonstrate that the survival of this
entire model microbial community is dependent on the regulatory system's
influence on the distribution of distinct cell states among individual cells
within a clonal population.
PMID- 28419705
TI - Intravoxel incoherent motion MRI for the differentiation of benign, intermediate,
and malignant solid soft-tissue tumors.
AB - PURPOSE: To determine the diagnostic potential of apparent diffusion coefficient
(ADC) and intravoxel incoherent motion (IVIM)-derived parameters for the
differentiation of benign, intermediate, and malignant solid soft-tissue tumors.
MATERIALS AND METHODS: The Institutional Review Board approved this prospective
study, and informed consent was obtained. IVIM imaging was performed in 64
patients including 44 benign, 6 intermediate, and 14 malignant solid soft-tissue
tumors at 1.5T. The IVIM parameters of the soft-tissue tumors were assessed using
the Kruskal-Wallis test. The diagnostic performance of the parameters was
evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The
ADC and true diffusion coefficient (D) values of malignancies (1.28 +/- 0.31,
1.06 +/- 0.23 [*10-3 mm2 /sec]) were significantly lower than those of
intermediate (1.49 +/- 0.54, 1.30 +/- 0.50 [*10-3 mm2 /sec]), or benign soft
tissue tumors (1.62 +/- 0.37, 1.36 +/- 0.33 [*10-3 mm2 /sec]) (P = 0.007 and P =
0.009, respectively). In the differential diagnosis of malignancies from benign
tumors, ADC demonstrated the highest area under the curve (Az) value (Az =
0.793). The perfusion fraction (f) values of intermediate soft-tissue tumors
(8.41 +/- 2.73) were significantly different from those of benign and malignant
tumors (14.70 +/- 5.37 [P = 0.002]; 14.44 +/- 5.31 [P = 0.021]). f showed the
highest Az value in differentiating intermediate from benign, and malignant soft
tissue tumors (Az = 0.90, and Az = 0.833, respectively). The pseudodiffusion
coefficient (D*) values of malignant soft-tissue tumors (144.40 +/- 24.88 [*10-3
mm2 /sec]) were significantly higher than those of benign tumors (124.96 +/-
26.24 [*10-3 mm2 /sec]) (P = 0.019). CONCLUSION: IVIM imaging may be helpful for
differentiating benign, intermediate, and malignant solid soft-tissue tumors.
LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
2017;46:1611-1618.
PMID- 28419707
TI - Current Resources for Evidence-Based Practice, March/April 2017.
PMID- 28419708
TI - Willingness to Pay for a Maternity Waiting Home Stay in Zambia.
AB - INTRODUCTION: Complications of pregnancy and childbirth can pose serious risks to
the health of women, especially in resource-poor settings. Zambia has been
implementing a program to improve access to emergency obstetric and neonatal
care, including expansion of maternity waiting homes-residential facilities
located near a qualified medical facility where a pregnant woman can wait to give
birth. Yet it is unclear how much support communities and women would be willing
to provide to help fund the homes and increase sustainability. METHODS: We
conducted a mixed-methods study to estimate willingness to pay for maternity
waiting home services based on a survey of 167 women, men, and community elders.
We also collected qualitative data from 16 focus group discussions to help
interpret our findings in context. RESULTS: The maximum willingness to pay was
5.0 Zambian kwacha or $0.92 US dollars per night of stay. Focus group discussions
showed that willingness to pay is dependent on higher quality of services such as
food service and suggested that the pricing policy (by stay or by night) could
influence affordability and use. DISCUSSION: While Zambians seem to value and be
willing to contribute a modest amount for maternity waiting home services,
planners must still address potential barriers that may prevent women from
staying at the shelters. These include cash availability and affordability for
the poorest households.
PMID- 28419710
TI - Updates From the Literature, March/April 2017.
PMID- 28419709
TI - Job Satisfaction and Subjective Well-Being Among Midwives: Analysis of a
Multinational Cross-Sectional Survey.
AB - INTRODUCTION: There is a considerable amount of empirical evidence to indicate a
positive association between an employee's subjective well-being and workplace
performance and job satisfaction. Compared with nursing research, there is a
relative lack of consistent scientific evidence concerning midwives' subjective
well-being and its determinants related to domains of job satisfaction. The
purpose of the study was to examine the association between the domains of job
satisfaction and components of subjective well-being in hospital midwives.
METHODS: This cross-sectional descriptive study involved 1190 hospital midwives
from 7 countries. Job satisfaction was measured by the McCloskey/Mueller
Satisfaction Scale. Subjective well-being was conceptualized in the study by the
2 components (the affective and the cognitive component). The affective component
of subjective well-being (ie, emotional well-being) was assessed by the Positive
and the Negative Affect Scale. The cognitive component of subjective well-being
(ie, life satisfaction) was measured by the Personal Well-Being Index. Pearson
correlations and multiple regression analyses were used to determine associations
between variables. RESULTS: Findings from correlation and regression analyses
indicated an overall weak association between the domains of job satisfaction and
components of subjective well-being. Satisfaction with extrinsic rewards,
coworkers, and interaction opportunities accounted for only 13% of variance in
the cognitive component (life satisfaction). The affective component (emotional
well-being) was weakly associated with satisfaction with control and
responsibility. DISCUSSION: The low amount of variance suggests that neither
component of subjective well-being is influenced by the domains of job
satisfaction. Further studies should focus on identifying other predictors of
subjective well-being among midwives. A better understanding of how specific job
facets are related to the subjective well-being of midwives might assist
employers in the design of counseling and intervention programs for subjective
well-being of midwives in the workplace and workplace performance.
PMID- 28419711
TI - Writing for the Journal of Midwifery & Women's Health: Beyond Research.
PMID- 28419712
TI - Comparison of safety and efficacy of image-guided enema reduction techniques for
paediatric intussusception: A review of the literature.
AB - There is variable international practice regarding the technique used for image
guided enema reduction in paediatric intussusception. A recent meta-analysis
found pneumatic reduction to be more effective than hydrostatic techniques.
Clinical practice variation may impact on perforation rates, ionizing radiation
exposure and requirement for surgery. The aim of this study was to review the
literature regarding the efficacy and safety of fluoroscopically guided pneumatic
reduction (FGPR) compared to ultrasound (US) guided intussusception reduction
(USGIR) techniques for paediatric intussusception treatment. Articles were
identified by searching OVID Medline on 21/02/14 and by scanning retrieved
articles reference lists. The search was repeated on 30/09/15. Systematic reviews
(SR) were appraised with the PRISMA critical appraisal tool. Primary studies
underwent a separate critical appraisal process. Successful reductions and
perforations per attempt were calculated for each study. Pooled estimates of
proportions were calculated for each of these dichotomous outcomes. A SR and 42
primary studies were included in the review. No randomised control trial (RCT)
study was included. Non-randomised comparative studies and non-comparative
studies suggest that hydrostatic reduction under US control has a similar
efficacy and safety profile to pneumatic reduction under fluoroscopic control,
but USGIR data are dominated by a single large, non-comparative study performed
in China. US-guided intussusception reduction should be considered an alternative
to FGPR as it has similar efficacy and safety, and affords no ionised radiation
exposure. However, RCT data are required to inform practice.
PMID- 28419713
TI - NT-proBNP predicts mortality in adults with transposition of the great arteries
late after Mustard or Senning correction.
AB - OBJECTIVE: The patients after Mustard and Senning corrections of transposition of
the great arteries (TGA) are at an increased risk of unexpected death. The aim of
this study was to identify markers allowing risk stratification of patients after
atrial switch correction of TGA to provide them with optimum care. METHODS AND
RESULTS: In this study, 87 patients were retrospectively evaluated after atrial
switch correction of TGA followed-up between 2005 and 2015. The mortality during
the follow-up was 9% (8 cardiac deaths). Markers significantly predictive of
death using univariable Cox proportional hazard ratio survival analysis were: N
terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction and end
diastolic dimension of the systemic right ventricle, mitral E, e', and s'.
Surprisingly, the Doppler parameters of mitral valve in subpulmonary ventricle
were more important for prognosis than those of systemic tricuspid valve. In
multivariable analysis, the only independent predictors of mortality were NT
proBNP (P = .00048; AUC 0.97) and the velocity of early diastolic filling (mitral
E) in subpulmonary ventricle (P = .01815; AUC 0.81). According to Kaplan-Meier
survival analysis, patients with NT-proBNP > 1000 pg/ml are at high risk of
death. Patients with mitral E < 68 cm/s are also at an increased risk of death.
CONCLUSIONS: NT-proBNP is the most reliable prognostic mortality factor and
should be measured regularly in TGA patients after Mustard or Senning correction.
Diastolic filling velocity of the subpulmonary left ventricle (mitral E) may be
more important for prognosis than systolic function of the systemic right
ventricle.
PMID- 28419714
TI - Young people's beliefs about the risk of bowel cancer and its link with physical
activity.
AB - OBJECTIVES: The primary objective was to explore young people's risk appraisals
of bowel cancer, including whether they had a coherent understanding of the
protective effects of physical activity (PA). A secondary objective was to
examine whether the illness risk representations (IRRs) framework could be used
to understand beliefs underlying bowel cancer risk appraisals. DESIGN:
Qualitative. METHODS: Framework analysis of semi-structured interviews with 19
people aged 14-17 years. RESULTS: Participants judged their risk of getting bowel
cancer as low. This was based on a lack of family history of cancer and their
current lifestyle behaviours, which were viewed as having a protective effect, or
because they planned on making change to their lifestyle in the future when
disease risk became more relevant. Participants were not aware of, and struggled
to understand, the link between PA and bowel cancer. They also lacked knowledge
of the effects of, or treatments for, bowel cancer. Beliefs underlying judgements
about the risk of bowel cancer fitted the IRR framework reasonably well.
CONCLUSIONS: The present research suggests that interventions designed to
increase PA with a view to reducing the risk of bowel cancer should aim to make
the future risk of bowel cancer feel more tangible, help young people to
understand the full range of consequences, explain how and why preventative
behaviours such as PA are effective in reducing risk, and emphasize that the
typical late presentation of symptoms, and therefore investigation by health care
services, reduces treatability. Statement of contribution What is already known
on this subject? Physical activity (PA) performed throughout the lifespan can
have a protective effect on bowel cancer, but levels of PA are low among young
people. Changing beliefs about the risk of getting bowel cancer may be a useful
strategy in motivating PA. What does this study add? Increased understanding of
how young people think about bowel cancer and the relationship between PA and
cancer. Identification of strategies for increasing young adults' appraisals of
the likelihood and severity of bowel cancer. Evidence to support the validity of
illness risk representations framework.
PMID- 28419715
TI - A survey on faculty perspectives on the transition to a biochemistry course-based
undergraduate research experience laboratory.
AB - It will always remain a goal of an undergraduate biochemistry laboratory course
to engage students hands-on in a wide range of biochemistry laboratory
experiences. In 2006, our research group initiated a project for in silico
prediction of enzyme function based only on the 3D coordinates of the more than
3800 proteins "of unknown function" in the Protein Data Bank, many of which
resulted from the Protein Structure Initiative. Students have used the ProMOL
plugin to the PyMOL molecular graphics environment along with BLAST, Pfam, and
Dali to predict protein functions. As young scientists, these undergraduate
research students wanted to see if their predictions were correct and so they
developed an approach for in vitro testing of predicted enzyme function that
included literature exploration, selection of a suitable assay and the search for
commercially available substrates. Over the past two years, a team of faculty
members from seven different campuses (California Polytechnic San Luis Obispo,
Hope College, Oral Roberts University, Rochester Institute of Technology, St.
Mary's University, Ursinus College, and Purdue University) have transferred this
approach to the undergraduate biochemistry teaching laboratory as a Course-based
Undergraduate Research Experience. A series of ten course modules and eight
instructional videos have been created (www.promol.org/home/basil-modules-1) and
the group is now expanding these resources, creating assessments and evaluating
how this approach helps student to grow as scientists. The focus of this
manuscript will be the logistical implications of this transition on campuses
that have different cultures, expectations, schedules, and student populations.
(c) 2017 by The International Union of Biochemistry and Molecular Biology,
45(5):426-436, 2017.
PMID- 28419716
TI - Effect of dehydration and rehydration intervals on fracture resistance of
reattached tooth fragments using a multimode adhesive.
AB - BACKGROUND/AIMS: The tooth fragment bonding technique, frequently used to restore
traumatized teeth, may be affected by dehydration/rehydration periods. The aim of
this study was to evaluate the effects of different dry and wet storage intervals
on multimode adhesive bonding between reattached fragments and teeth. MATERIALS
AND METHODS: Eighty-four bovine incisors were fractured and randomized into
groups (n=12). After teeth fracturing, each specimen was assigned to one of the
following groups: G0: control group (sound tooth); GA1 and GA2: 1-h dehydration
and a 15-min or 24-hours rewetting period, respectively; GB1 and GB2: 24-hours
dehydration and a 15-minutes or 24-hours rewetting period, respectively; and GC:
1-hour (GC1) or 24-hours (GC2) dehydration period only. Tooth fragments were then
reattached using a multimode adhesive in a self-mode technique with a flowable
resin composite. The fracture resistance was evaluated in a universal testing
machine under a compressive load (1 mm/min-1 ). Data were submitted to two-way
analysis of variance and post hoc Tukey test (5%). RESULTS: No significant
interaction between dehydration and rehydration intervals was observed (P>.05).
Only the step of rehydration significantly affected the reattachment strength
when compared to the groups submitted only to dehydration, regardless of the
interval (15 minutes or 24 hours). CONCLUSION: Rehydrating a tooth fragment for
15 minutes before bonding with a multimode adhesive maintained sufficient
moisture to increase reattachment strength.
PMID- 28419717
TI - Ligand recognition properties of the vasopressin V2 receptor studied under QSAR
and molecular modeling strategies.
AB - The design of new drugs that target vasopressin 2 receptor (V2R) is of vital
importance to develop new therapeutic alternatives to treat diseases such as
heart failure, polycystic kidney disease. To get structural insights related to
V2R-ligand recognition, we have used a combined approach of docking, molecular
dynamics simulations (MD) and quantitative structure-activity relationship (QSAR)
to elucidate the detailed interaction of the V2R with 119 of its antagonists. The
three-dimensional model of V2R was built by threading methods refining its
structure through MD simulations upon which the 119 ligands were subjected to
docking studies. The theoretical results show that binding recognition of these
ligands on V2R is diverse, but the main pharmacophore (electronic and pi-pi
interactions) is maintained; thus, this information was validated under QSAR
results. QSAR studies were performed using MLR analysis followed by ANN analysis
to increase the model quality. The final equation was developed by choosing the
optimal combination of descriptors after removing the outliers. The applicability
domains of the constructed QSAR models were defined using the leverage and
standardization approaches. The results suggest that the proposed QSAR models can
reliably predict the reproductive toxicity potential of diverse chemicals, and
they can be useful tools for screening new chemicals for safety assessment.
PMID- 28419718
TI - Shifting microbial communities sustain multiyear iron reduction and
methanogenesis in ferruginous sediment incubations.
AB - Reactive Fe(III) minerals can influence methane (CH4 ) emissions by inhibiting
microbial methanogenesis or by stimulating anaerobic CH4 oxidation. The balance
between Fe(III) reduction, methanogenesis, and CH4 oxidation in ferruginous
Archean and Paleoproterozoic oceans would have controlled CH4 fluxes to the
atmosphere, thereby regulating the capacity for CH4 to warm the early Earth under
the Faint Young Sun. We studied CH4 and Fe cycling in anoxic incubations of
ferruginous sediment from the ancient ocean analogue Lake Matano, Indonesia, over
three successive transfers (500 days in total). Iron reduction, methanogenesis,
CH4 oxidation, and microbial taxonomy were monitored in treatments amended with
ferrihydrite or goethite. After three dilutions, Fe(III) reduction persisted only
in bottles with ferrihydrite. Enhanced CH4 production was observed in the
presence of goethite, highlighting the potential for reactive Fe(III) oxides to
inhibit methanogenesis. Supplementing the media with hydrogen, nickel and
selenium did not stimulate methanogenesis. There was limited evidence for Fe(III)
dependent CH4 oxidation, although some incubations displayed CH4 -stimulated
Fe(III) reduction. 16S rRNA profiles continuously changed over the course of
enrichment, with ultimate dominance of unclassified members of the order
Desulfuromonadales in all treatments. Microbial diversity decreased markedly over
the course of incubation, with subtle differences between ferrihydrite and
goethite amendments. These results suggest that Fe(III) oxide mineralogy and
availability of electron donors could have led to spatial separation of Fe(III)
reducing and methanogenic microbial communities in ferruginous marine sediments,
potentially explaining the persistence of CH4 as a greenhouse gas throughout the
first half of Earth history.
PMID- 28419719
TI - Spectroscopic evidences of toxic trans-crotonaldehyde trapped and transformed by
resveratrol to prevent the damage of mitochondrial DNA.
AB - The purpose of this study is to probe the spectroscopic evidences of toxic trans
crotonaldehyde (TCA) trapped and transformed by resveratrol (Res) to prevent the
damage of mitochondrial DNA. In aldehyde dehydrogenase (ALDH) at the different pH
or mitochondria, the spectroscopic characteristics of TCA trapped and transformed
by Res were observed by means of both UV-vis and Raman spectra. When Res
interacted with TCA, TCA peak at 316 nm immediately disappeared while Res main
peak at 305 nm and shoulder peak at 320 nm were dramatically changed, Raman peaks
of TCA at 1,688 cm-1 assigned to CH?O and 1,641 cm-1 affiliated to C?C were
strikingly shifted, Raman peaks of Res itself were significantly displaced or
disappeared, especially in mitochondria and ALDH at different pH. The active
groups of Res were the ?OH at C5 and C10 . The results of theoretical
calculations are in agreement on the whole with the experimental data. The Res
plays undoubtedly an important role via the structural change in TCA. The toxic
CH?O of TCA was effectively trapped and transformed by Res by means of itself ?OH
at C5 and C10 . The mitochondrial alkaline microenvironment and ALDH promoted the
elimination of toxic TCA. (c) 2017 IUBMB Life, 69(7):500-509, 2017.
PMID- 28419720
TI - Illusory hand ownership in a patient with personal neglect for the upper limb,
but no somatoparaphenia.
AB - The symptoms of patients with left personal neglect are characterized by
inattention towards contralesional (left) body parts while at the same time
explicitly ascertaining ownership for the neglected hemibody. It is currently
unknown if personal neglect is associated with more subtle or implicit
disturbances of own body perception and body ownership as measured with the
rubber hand illusion. In this study, we report data from a patient with a right
hemispheric lesion and personal neglect, without associated somatosensory
deficits. We administered to the patient (and to 12 age-matched controls) the
rubber hand illusion paradigm to the right and left hands, to elicit illusory
ownership for a fake hand, before and after recovery from personal neglect for
the left arm. In a first session, run when the patient showed personal neglect
affecting the left arm, he experienced a significantly enhanced subjective
illusion of embodiment for the left fake hand as compared to the right hand (as
assessed through a standard questionnaire). After recovery from personal neglect
for the left arm (second session), the results of the left and right rubber hand
illusion experiments were comparable, with no modulation of hand ownership. We
argue that personal neglect may consist not only in an inattentional disorder,
but also in a deficit of multisensory body representation characterized by a high
sensitivity to experimental manipulations of subjective aspects of body
ownership.
PMID- 28419721
TI - Classical image of the pulmonary artery aneurysm secondary to idiopathic
pulmonary hypertension.
PMID- 28419722
TI - Role of monocyte tissue factor on patients with non-small cell lung cancer.
AB - BACKGROUND: To examine the expression of D-dimer, fibrinogen (FIB), leukocyte, C
reactive protein (CRP) and tissue factor (TF) released from monocyte in non-small
cell lung cancer (NSCLC) patients with or without venous thromboembolism (VTE)
and analyse the correlation, to explore the possible mechanisms. METHODS: Seventy
two patients confirmed the diagnosis of lung cancer, among whom 10 with VTE were
enrolled into the study from November 2012 to January 2014 in the First
Affiliated Hospital of Fujian Medical University and 30 healthy subjects were
also enrolled as the control group. Ficoll and Percoll density gradient
centrifugation separated of peripheral blood monocyte. Monocyte TF mRNA
expression was detected using reverse transcriptase-polymerase chain reaction (RT
PCR). RESULTS: There were significant differences in different stages of the
cancer (P < .05) and no significance among the histopathologic types (P > .05)
for the expression of monocyte TF mRNA in NSCLC patients, its expression was
significantly higher in cancer with lymph node metastasis than those without
lymph node metastasis (P < .01). Meanwhile, in NSCLC patients with VTE, the
expression of monocyte TF mRNA was significantly higher than that in patients
without VTE (P < .01). Difference of the survival curves between the low monocyte
TF mRNA expression and the high monocyte TF mRNA expression was significant (Log
rank x2 = 4.923, P < .05). CONCLUSIONS: Monocyte TF may be a relevant source of
TF-mediated thrombogenicity in NSCLC patients and may be associated with
prognosis in NSCLC.
PMID- 28419723
TI - Characteristics and outcomes of ALK+ non-small cell lung cancer patients in
Korea.
AB - AIM: This study aimed to describe characteristics, treatment patterns and
survival among Korean patients diagnosed with locally advanced or metastatic
anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A
retrospective patient chart review was conducted in major cancer centers in Korea
in 2014-2015. Participating physicians reviewed patient charts and reported
characteristics, treatment patterns, clinician-defined progression-free survival
(PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC
patients. PFS and OS were estimated using Kaplan-Meier analysis. RESULTS:
Physicians reported on 55 ALK+ NSCLC patients. Median age at locally advanced or
metastatic NSCLC diagnosis was 60 years. Most patients (82%) received initial
chemotherapy; 13% received an ALK inhibitor in the first line; 62% received an
ALK inhibitor by the end of follow-up. Of the 30 patients who received
crizotinib, 83% discontinued and 13% died during crizotinib therapy. Median PFS
on crizotinib was 6.7 months. Of those who discontinued, 32% switched to
chemotherapy, 16% switched to a different ALK inhibitor and 52% received no
further therapy. After discontinuing crizotinib, median OS was 6.0 months
overall, and 3.4 months among patients who did not receive a second-generation
ALK inhibitor. CONCLUSION: In this study of locally advanced or metastatic ALK+
NSCLC patients in Korea, roughly one-third did not receive an ALK inhibitor.
Among patients who discontinued crizotinib, over half received no further
antineoplastic therapy and OS was poor, particularly among patients without
second-generation ALK inhibitor use. These findings suggest a need for greater
access to effective treatments following crizotinib discontinuation for ALK+
NSCLC patients in Korea.
PMID- 28419724
TI - A Reversed Photosynthesis-like Process for Light-Triggered CO2 Capture, Release,
and Conversion.
AB - Materials for CO2 capture have been extensively exploited for climate governance
and gas separation. However, their regeneration is facing the problems of high
energy cost and secondary CO2 contamination. Herein, a reversed photosynthesis
like process is proposed, in which CO2 is absorbed in darkness while being
released under light illumination. The process is likely supplementary to natural
photosynthesis of plants, in which, on the contrary, CO2 is released during the
night. Remarkably, the material used here is able to capture 9.6 wt.% CO2
according to its active component. Repeatable CO2 capture at room temperature and
release under light irradiation ensures its convenient and cost-effective
regeneration. Furthermore, CO2 released from the system is successfully converted
into a stable compound in tandem with specific catalysts.
PMID- 28419725
TI - Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia:
Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin
Initiators.
AB - OBJECTIVE: To examine medication adherence and healthcare costs for combination
prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs.
monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin)
among patients with fibromyalgia syndrome (FMS). METHODS: Our retrospective
cohort study used claims data for the South Carolina Blue Cross Blue Shield State
Health Plan (SHP). Patients with FMS >= 18 years of age, with prescription
initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12
months pre- and post-index periods were included (combination: n = 100;
pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n =
272). Medication adherence measures included high adherence (medication
possession ratio >= 80%) and total supply days. Healthcare costs comprised direct
medical expenditures. Propensity score methods of inverse probability of
treatment weights were used to control for selection bias due to differing pre
index characteristics. RESULTS: Odds ratios for high adherence were significantly
increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15),
duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply
days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23),
duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health
care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291
vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs.
$16,857) cohorts. CONCLUSIONS: Medication adherence was considerably better for
combination prescription initiators; however, expenditures for total health care
were higher. Still, our findings suggest important clinical benefits with the use
of combination prescription therapy, and prospective studies of medication
adherence are warranted to examine causal relationships with outcomes not
captured by healthcare claims databases.
PMID- 28419726
TI - Chemotaxonomic characterisation of the thaumarchaeal lipidome.
AB - Thaumarchaeota are globally distributed and abundant microorganisms occurring in
diverse habitats and thus represent a major source of archaeal lipids. The scope
of lipids as taxonomic markers in microbial ecological studies is limited by the
scarcity of comparative data on the membrane lipid composition of cultivated
representatives, including the phylum Thaumarchaeota. Here, we comprehensively
describe the core and intact polar lipid (IPL) inventory of ten ammonia-oxidising
thaumarchaeal cultures representing all four characterized phylogenetic clades.
IPLs of these thaumarchaeal strains are generally similar and consist of membrane
spanning, glycerol dibiphytanyl glycerol tetraethers with monoglycosyl,
diglycosyl, phosphohexose and hexose-phosphohexose headgroups. However, the
relative abundances of these IPLs and their core lipid compositions differ
systematically between the phylogenetic subgroups, indicating high potential for
chemotaxonomic distinction of thaumarchaeal clades. Comparative lipidomic
analyses of 19 euryarchaeal and crenarchaeal strains suggested that the lipid
methoxy archaeol is synthesized exclusively by Thaumarchaeota and may thus
represent a diagnostic lipid biomarker for this phylum. The unprecedented
diversity of the thaumarchaeal lipidome with 118 different lipids suggests that
membrane lipid composition and adaptation mechanisms in Thaumarchaeota are more
complex than previously thought and include unique lipids with as yet unresolved
properties.
PMID- 28419727
TI - Endotoxin testing of a wound debridement device containing medicinal Lucilia
sericata larvae.
AB - Alimentary products of medicinal Lucilia sericata larvae are studied to determine
their mechanisms of action, particularly in the contexts of wound debridement and
disinfection. Furthermore, the larvae can be applied to patients in contained
medical devices (such as the BioBag; BioMonde). Here, we tested the materials and
larval content of the most commonly used debridement device (the "BB-50") to
explore the possibility that endotoxins may be contributing to the bio-activity
of the product, given that endotoxins are potent stimulants of cellular
activation. Using standardised protocols to collect larval alimentary products
(LAP), we proceeded to determine residual endotoxin levels in LAP derived from
the device, before and after the neutralisation of interfering enzymatic
activity. The debridement device and its associated larval content was not a
significant source of lipopolysaccharide (LPS) activity. However, it is clear
from these experiments that a failure to remove the confounding serine proteinase
activity would have resulted in spuriously high and erroneous results. The
residual LPS levels detected are unlikely to be active in wound healing assays,
following cross-referencing to publications where LPS at much higher levels has
been shown to have positive and negative effects on processes associated with
wound repair and tissue regeneration.
PMID- 28419728
TI - Temporal changes in cutaneous bacterial communities of terrestrial- and aquatic
phase newts (Amphibia).
AB - Animal-associated bacterial communities play essential roles for their host's
ecology, physiology and health. Temporal dynamics of these communities are poorly
understood, but might be of high relevance for amphibians with a well-expressed
biphasic biology of adults where the structure of their skin changes drastically
between the aquatic and terrestrial phases. Here, we investigated the temporal
dynamics of cutaneous bacterial communities of Lissotriton boscai and Triturus
marmoratus by monthly sampling populations from a pond and surrounding
terrestrial habitats near A Coruna, Spain. These communities were characterized
by 16S rRNA gene amplicons from DNA isolated from skin swabs. Newt bacterial
communities displayed variation at three levels: between larvae and aquatic
adults, between adult life phases (terrestrial versus aquatic), and temporally
within life phases. The skin bacterial communities tended to differ to a lesser
extent temporally and between larvae and adults, and more strongly between life
phases. Larvae had a higher proportion of reads associated with antifungal taxa
compared with adults, while no differences were found among adult life phases.
Terrestrial specimens exhibited the highest community diversity. The regular
transitions of adult newts between aquatic and terrestrial environments might
contribute to the diversity of their skin microbiota and could increase disease
resistance.
PMID- 28419729
TI - Prevalence and Predictors of Patient Nonadherence to Pharmacological Acute Pain
Therapy at Home After Day Surgery: A Prospective Cohort Study.
AB - BACKGROUND: Good adherence to prescribed analgesics can be crucial to suppress or
even prevent acute postoperative pain after day surgery. The aim of this study
was to analyze prevalence and predictors of analgesic nonadherence after day
surgery. METHODS: Elective patients scheduled for day surgery were prospectively
enrolled from November 2008 to April 2010. Outcome parameters were measured by
using questionnaire packages at 2 time points: 1 week preoperatively and 4 days
postoperatively. The primary outcome parameter was analgesic nonadherence.
Adherence was defined according to the patient's response to the questionnaire
item "analgesia use as prescribed": full adherence, "yes"; partial adherence,
"yes, sometimes"; nonadherence, "no." Bivariate and multivariate logistic
regression analyses were performed to identify predictors of analgesic
nonadherence. RESULTS: A total of 1,248 patients were included. The prevalence
rates of analgesic nonadherence and partial adherence were 21.6% and 20.0%,
respectively, in the total study population but dropped to 9.4% and 19.8%,
respectively, in patients with moderate to severe pain. Low postoperative pain
intensity and short duration of surgery were the most important predictors of
analgesic nonadherence. The most important preoperative predictors for analgesic
nonadherence were low preoperative pain intensity, low preoperative expectations
of pain, and low fear of short-term effects of surgery. CONCLUSION: Analgesic
nonadherence and partial adherence are common after day surgery but decrease as
average pain intensity increases. Patients at risk for analgesic nonadherence can
be identified during the preoperative period based on preoperative pain
intensity, preoperative expectations of pain, and fear of surgery.
PMID- 28419730
TI - Low-Temperature Modification of ZnO Nanoparticles Film for Electron-Transport
Layers in Perovskite Solar Cells.
AB - An electron-transport layer (ETL) that selectively collects photogenerated
electrons is an important constituent of halide perovskite solar cells (PSCs).
Although TiO2 films are widely used as ETL of PSCs, the processing of TiO2 films
with high electron mobility requires high-temperature annealing and TiO2
dissociates the perovskite layer through a photocatalytic reaction. Here, we
report an effective surface-modification method of a room-temperature processed
ZnO nanoparticles (NPs) layer as an alternative to the TiO2 ETL. A combination of
simple UV exposure and nitric acid treatment effectively removes the hydroxyl
group and passivates surface defects in ZnO NPs. The surface modification of ZnO
NPs increases the power conversion efficiency (PCE) of PSCs to 14 % and decreases
the aging of PSCs under light soaking. These results suggest that the surface
modified ZnO film can be a good ETL of PSCs and provide a path toward low
temperature processing of efficient and stable PSCs that are compatible with
flexible electronics.
PMID- 28419731
TI - A qualitative study of doctors' and nurses' barriers to communicating with
seriously ill patients about their dependent children.
AB - OBJECTIVE: Research indicates that health personnel caring for seriously ill
patients with dependent children aged 0 to 18 years often avoid discussing with
them the challenges of being a family with a parent in treatment. Children of
seriously ill patients risk serious trauma and emotional difficulty later in life
and depend on adult support to minimize these consequences. Patients suffer
anxiety about supporting their children during their illness. Because of their
potentially pivotal role in supporting patients in enabling parent-child
communication, we examined HP's structural and emotional barriers to
communicating with patients about their children. METHODS: The study was based on
49 semi-structured, in-depth interviews with doctors and nurses working with
haematology, gynaecological cancer, and neurointensive care. Both interviews and
analysis addressed emotional and structural barriers, drawing on the theoretical
framework of Maturana's domains. RESULTS: The study found structural barriers
(eg, lack of space in the medical recording system, professional code, time
pressure, and lack of training) and emotional barriers (eg, the painful nature of
the situation and the perceived need of keeping professional distance). We found
that emotional barriers tended to grow when structural barriers were not
addressed. CONCLUSIONS: Our study indicates (1) the need to use templates and
manual procedures to gather and process information about children in medical
records; (2) the need for managerial backing for addressing children of seriously
ill patients and time spent on it; and (3) the need for future HP training
programmes to include how to implement procedures and how to address all
barriers.
PMID- 28419732
TI - A Phase 1 Randomized, Placebo-Controlled Study Assessing the Pharmacokinetics,
Safety, and Tolerability of Retosiban in Healthy, Nonpregnant Japanese Subjects.
AB - This study characterized the pharmacokinetics, safety, and tolerability of
retosiban in healthy, nonpregnant Japanese women prior to the enrollment of
Japanese women in preterm labor in phase 3 trials. This study had 2 cohorts.
Cohort 1 was a double-blind, sponsor-open, randomized study in Japanese women.
Cohort 2 was an open-label study in white women to compare the pharmacokinetics
with those of Japanese women. Retosiban was administered as a 6 mg/h infusion for
24 hours, followed by a 12 mg/h infusion over the next 24 hours; each infusion
was preceded by a 6 mg loading dose administered over 5 minutes. Plasma
concentrations of retosiban and its major metabolite, GSK2847065, were determined
with an informal comparison of pharmacokinetics between Japanese and white women.
There was minimal difference in exposure to retosiban or GSK2847065 between
Japanese and white women (ratio of 1.03 in retosiban AUC and Cmax ). The 2 doses
of retosiban were well tolerated across both populations, and no ethnic
difference was observed in the safety profile. Given the results of this study
and the known safety profile and dosing flexibility in the phase 3 trials, ethnic
specific dose adjustment of retosiban is not considered necessary for the
Japanese and general Asian population.
PMID- 28419733
TI - Interphotoreceptor matrix based biomaterial: Impact on human retinal progenitor
cell attachment and differentiation.
AB - While cell transplantation therapies show great promise as treatments for retinal
degeneration, the challenge of low cell survival upon transplantation motivates
exploration of materials that may serve as cell delivery vehicles and promote
survival and differentiation. In this study, we explored the native matrix that
surrounds the outer segments of photoreceptors and promotes their homeostasis,
interphotoreceptor matrix (IPM), as a substrate for human retinal progenitor
cells (hRPCs). Bovine IPM was characterized to determine its structure and
biochemical composition, and processed to develop substrates for cells. Cell
viability, morphology, proliferation and expression of photoreceptors marker
genes were studied on IPM-based substrates in vitro. We explored different
preparations of IPM as a scaffold. Lectin staining revealed that a distinct
honeycomb structure of native IPM is lost during centrifugation to prepare a more
concentrated suspension of matrix. Biochemical analysis of bovine IPM indicated
presence of glycosaminoglycans and proteins. IPM mediated hRPC attachment and
spreading with no signs of cytotoxicity. Cells proliferated more on native IPM
substrates compared to IPM that was centrifuged to create a concentrated
suspension. Cells cultured on IPM substrates expressed markers of photoreceptors:
rhodopsin, NRL and ROM1. Together this data supports further exploration of IPM
as a tool for retinal tissue engineering. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater, 106B: 891-899, 2018.
PMID- 28419735
TI - Hospital use in Aboriginal and non-Aboriginal patients with chronic disease.
AB - OBJECTIVE: The objective of this study was to compare rates of hospital
utilisation in Aboriginal and non-Aboriginal peoples before and after hospital
admission for chronic obstructive pulmonary disease, heart failure and/or type 2
diabetes mellitus. METHODS: This was a longitudinal cohort study from 2002 to
2014, which was conducted in all hospitals in Western Australia. The participants
of this study were Aboriginal and non-Aboriginal patients with a principal
diagnosis of heart failure, type 2 diabetes or chronic obstructive pulmonary
disease, on admission to hospital, where such an event had not occurred in the
previous 3 years. Inpatient days and ED presentations were the main outcome
measures. RESULTS: Among the patients with chronic disease, Aboriginal people
have similar inpatient days for all causes compared to non-Aboriginal people.
However, they have much higher ED presentations in comparison. Age of onset of
cardinal events occurs 15-20 years earlier in Aboriginal patients with chronic
disease. Although age has little influence on ED presentations in non-Aboriginal
chronic disease patients, younger Aboriginal people with chronic disease present
far more often to ED than older Aboriginal people. CONCLUSIONS: Aboriginal people
use health services in a different manner when compared to non-Aboriginal people.
In a subset of patients with chronic disease, high use may be reduced with better
access to primary healthcare. Policy-makers and healthcare providers should
examine healthcare use from primary to tertiary care among the Aboriginal
population, with a particular focus on ED presentations; investigate the
underlying causes driving specific patterns of health service utilisation among
Aboriginal people; and develop interventions to reduce potential deleterious
impacts, and enhance the potential benefits, of specific patterns of healthcare
use.
PMID- 28419736
TI - Changes.
PMID- 28419734
TI - The life sulfuric: microbial ecology of sulfur cycling in marine sediments.
AB - Almost the entire seafloor is covered with sediments that can be more than 10 000
m thick and represent a vast microbial ecosystem that is a major component of
Earth's element and energy cycles. Notably, a significant proportion of microbial
life in marine sediments can exploit energy conserved during transformations of
sulfur compounds among different redox states. Sulfur cycling, which is primarily
driven by sulfate reduction, is tightly interwoven with other important element
cycles (carbon, nitrogen, iron, manganese) and therefore has profound
implications for both cellular- and ecosystem-level processes. Sulfur
transforming microorganisms have evolved diverse genetic, metabolic, and in some
cases, peculiar phenotypic features to fill an array of ecological niches in
marine sediments. Here, we review recent and selected findings on the microbial
guilds that are involved in the transformation of different sulfur compounds in
marine sediments and emphasise how these are interlinked and have a major
influence on ecology and biogeochemistry in the seafloor. Extraordinary
discoveries have increased our knowledge on microbial sulfur cycling, mainly in
sulfate-rich surface sediments, yet many questions remain regarding how sulfur
redox processes may sustain the deep-subsurface biosphere and the impact of
organic sulfur compounds on the marine sulfur cycle.
PMID- 28419737
TI - A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a
Hospital-wide Population of Patients Receiving Conventional Dosing: Is there
Enough Evidence for Suggesting TDM in the Majority of Patients?
AB - A retrospective study was conducted to assess our 10-year experience of
therapeutic drug monitoring (TDM) of linezolid in a large patient population to
establish whether conventional dosing may result in adequate drug exposure in the
majority of patients. Patients included in this study underwent TDM of linezolid
trough concentration (Cmin ) during treatment with conventional doses of 600 mg
every 12 hr in the period between January 2007 and June 2016. The desired range
of Cmin was set between 2 and 7 mg/L (underexposure, Cmin < 2 mg/L;
overexposure, Cmin > 7 mg/L). Multivariate logistic regression analysis
investigated variables potentially correlated with linezolid Cmin . One thousand
and forty-nine patients had 2484 linezolid Cmin assessed during treatment with
conventional doses. Median (IQR) linezolid Cmin was 5.08 mg/L (2.78-8.52 mg/L).
Linezolid Cmin was within the desired range in 50.8% of cases (1262/2484).
Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n =
401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid
overexposure was significantly associated with CrCLC-G estimates <=40 mL/min. (OR
1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly
associated with CrCLC-G estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p <
0.001). Linezolid Cmin was not correlated linearly with CrCLC-G (R2 = 0.061).
Variability in renal function explained only partially the very wide
interindividual linezolid Cmin variability. Our study suggests that TDM could
represent a valuable approach in optimizing linezolid exposure in the majority of
patients.
PMID- 28419738
TI - Academic voice: On feminism, presence, and objectivity in writing.
AB - Academic voice is an oft-discussed, yet variably defined concept, and confusion
exists over its meaning, evaluation, and interpretation. This paper will explore
perspectives on academic voice and counterarguments to the positivist origins of
objectivity in academic writing. While many epistemological and methodological
perspectives exist, the feminist literature on voice is explored here as the
contrary position. From the feminist perspective, voice is a socially constructed
concept that cannot be separated from the experiences, emotions, and identity of
the writer and, thus, constitutes a reflection of an author's way of knowing. A
case study of how author presence can enhance meaning in text is included.
Subjective experience is imperative to a practice involving human interaction.
Nursing practice, our intimate involvement in patient's lives, and the nature of
our research are not value free. A view is presented that a visible presence of
an author in academic writing is relevant to the nursing discipline. The
continued valuing of an objective, colorless academic voice has consequences for
student writers and the faculty who teach them. Thus, a strategically used
multivoiced writing style is warranted.
PMID- 28419739
TI - Cardiac troponin T and fast skeletal muscle denervation in ageing.
AB - BACKGROUND: Ageing skeletal muscle undergoes chronic denervation, and the
neuromuscular junction (NMJ), the key structure that connects motor neuron nerves
with muscle cells, shows increased defects with ageing. Previous studies in
various species have shown that with ageing, type II fast-twitch skeletal muscle
fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres.
However, how this process is regulated is largely unknown. A better understanding
of the mechanisms regulating skeletal muscle fibre-type specific denervation at
the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac
troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component
of the mechanisms of muscle contraction. It is expressed in skeletal muscle
during early development, after acute sciatic nerve denervation, in various
neuromuscular diseases and possibly in ageing muscle. Yet the subcellular
localization and function of cTnT in skeletal muscle is largely unknown. METHODS:
Studies were carried out on isolated skeletal muscles from mice, vervet monkeys,
and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used
to analyse protein expression, real-time reverse transcription polymerase chain
reaction was used to measure gene expression, immunofluorescence staining was
performed for subcellular distribution assay of proteins, and electromyographic
recording was used to analyse neurotransmission at the NMJ. RESULTS: Levels of
cTnT expression in skeletal muscle increased with ageing in mice. In addition,
cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the
slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA)
RIalpha subunit was largely removed from, while PKA RIIalpha and RIIbeta are
enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch
muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i)
increased PKA RIalpha and reduced PKA RIIalpha at the NMJ; (ii) decreased the
levels of gene expression of muscle denervation markers; and (iii) enhanced
neurotransmission efficiency at NMJ. CONCLUSIONS: Cardiac troponin T at the NMJ
region contributes to NMJ functional decline with ageing mainly in the fast
twitch skeletal muscle through interfering with PKA signalling. This knowledge
could inform useful targets for prevention and therapy of age-related decline in
muscle function.
PMID- 28419740
TI - Pulmonary hypertension associated with combined fibrosing mediastinitis and
bronchial anthracofibrosis: A retrospective analysis in a single Chinese
hospital.
AB - INTRODUCTION: Both fibrosing mediastinitis (FM) and bronchial anthracofibrosis
(BAF) are unique diseases. The combined appearance of FM and BAF is extremely
rare. OBJECTIVES: The aim of this study was to investigate the clinical features
of patients with coexisting FM and BAF. METHOD: Between January 2003 and December
2015, a total of eight patients were diagnosed at the Peking Union Medical
College Hospital as having combined FM and BAF. The clinical presentations,
radiographic features and bronchoscopic findings of the eight patients were
reviewed. RESULTS: The patients were five women and three men with a median age
of 64 years (range 56-86 years). Symptoms included dyspnea (eight patients),
cough (seven patients), chest pain (two patients), hemoptysis (two patients) and
so on. Chest CT of all eight patients showed mediastinal soft-tissue lesions,
with multiple narrowed or obliterated lobar or segmental bronchi and arteries.
Bronchoscopy showed that all of the patients had multiple stenoses of lobar or
segmental bronchi with anthracotic pigmentation on the mucosa. Echocardiography
showed that all of the patients had elevated pulmonary arterial systolic pressure
(median 81 mm Hg, range 51-107 mm Hg). Each of the eight patients had a history
of exposure to, or infection with, tuberculosis, although there was no evidence
of active disease. All of the eight patients had long-term exposure to indoor
coal or biomass fuel smoke. CONCLUSIONS: FM can coexist with BAF, characterized
by prominent pulmonary hypertension. The possible etiological factors are
tuberculosis and coal or biomass fuel exposure.
PMID- 28419741
TI - Optimal treatment strategy for acute cholecystitis based on predictive factors:
Japan-Taiwan multicenter cohort study.
AB - BACKGROUND: Although early laparoscopic cholecystectomy is widely performed for
acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill
patients remains controversial. This study aims to determine the best practice
for the patients presenting with acute cholecystitis focused on disease severity
and comorbidities. METHODS: An international multicentric retrospective
observational study was conducted over a 2-year period. Patients were divided
into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy
after gallbladder drainage; Group C: gallbladder drainage alone; and Group D:
medical treatment alone. RESULTS: The subjects of analyses were 5,329 patients.
There were statistically significant differences in mortality rates between
patients with Charlson comorbidity index (CCI) scores below and above 6 (P <
0.001). The shortest operative time was observed in Group A patients who
underwent surgery 0-3 days after admission (P < 0.01). Multiple regression
analysis revealed CCI and low body mass index <20 as predictive factors of 30-day
mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and
respiratory dysfunction were predictive factors of 30-day mortality in Grade III
patients. In Grade III patients without predictive factors, there were no
difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A
patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%)
in cases with at least one predictive factor. CONCLUSION: Even patients with
Grade III severity, primary cholecystectomy can be performed safely if they have
no predictive factors of mortality. Gallbladder drainage may have a therapeutic
role in subgroups with higher CCI or higher disease severity.
PMID- 28419742
TI - A detachable laparoscopic bulldog clamp in laparoscopic-assisted colonoscopic
polypectomy - a video vignette.
PMID- 28419743
TI - Nonhealing ulcers on the scalp.
PMID- 28419744
TI - Establishment of an inferior vena cava filter database and interventional
radiology led follow-up - retrieval rates and patients lost to follow-up.
AB - INTRODUCTION: To evaluate the rates of inferior vena cava (IVC) filter retrieval
and the number of patient's lost to follow-up, before and after the establishment
of an IVC filter database and interventional radiology (inserting physician) led
follow-up. METHODS: On the 1st of June 2012, an electronic interventional
radiology database was established at our Institution. In addition, the
interventional radiology team took responsibility for follow-up of IVC filters.
Data were prospectively collected from the database for all patients who had an
IVC filter inserted between the 1st June 2012 and the 31st May 2014. Data on
patients who had an IVC filter inserted between the 1st of June 2009 to the 31st
of May 2012 were retrospectively reviewed. Patient demographics, insertion
indications, filter types, retrieval status, documented retrieval decisions, time
in situ, trackable events and complications were obtained in the pre-database (n
= 136) and post-database (n = 118) cohorts. RESULTS: Attempted IVC filter
retrieval rates were improved from 52.9% to 72.9% (P = 0.001) following the
establishment of the database. The number of patients with no documented decision
(lost to follow-up) regarding their IVC filter reduced from 31 of 136 (23%) to 0
of 118 patients (P = < 0.001). There was a non-significant reduction in IVC
filter dwell time in the post-database group (113 as compared to 137 days, P =
0.129). CONCLUSION: Following the establishment of an IVC filter database and
interventional radiology led follow-up, we demonstrate a significant improvement
in the attempted retrieval rates of IVC filters and the number of patient's lost
to follow-up.
PMID- 28419745
TI - Granulomatous variant of pigmented purpuric dermatosis: report of two cases and
review of the literature.
PMID- 28419746
TI - Factors for postoperative complications following pressure ulcer operation:
stepwise multiple logistic regression analysis.
AB - Patients with pressure ulcers are generally older, have a long hospital stay and
often have a variety of comorbidities. The decision to perform surgery for
pressure ulcer management can be difficult because of concerns about the risk of
postoperative complications. The aim of this study was to analyse the
relationship between comorbid conditions and surgical outcomes in order to guide
patient selection for pressure ulcer surgery. In 57 patients, data on age, defect
size, operating time, hospital stay, body mass index, surgical site, mobility
state, cardiac ischaemic history, diabetes, renal failure, ventilator dependency,
tracheostomy state, use of haemodilution therapy and cancer were evaluated using
stepwise multiple logistic regression analysis to determine the relationships
between variables. There were no postoperative cardiac ischaemic events. Wound
complications occurred in 8 patients (14%), pneumonia in 12 patients (21.1%) and
mortality in 1 patient (1.7%). The risk of postoperative pneumonia increased
1.069-fold in elderly patients (odds ratio = 1.069, P < 0.05) and increased 44.17
fold in preoperative ventilator users (odds ratio = 44.17, P < 0.05). The risk of
wound complication increased 1.012-fold with the presence of a larger defect site
(odds ratio = 1.012, P < 0.05) and increased 7.474-fold in patients who received
haemodilution therapy (odds ratio = 7.474, P < 0.05). Our results indicate that
most comorbid conditions did not significantly affect postoperative
cardiopulmonary or wound complications. However, the risk of postoperative
pneumonia increased in patients with ventilator use or old age, and the risk of
wound complication increased in patients with a large defect size and in those
who used haemodilution therapy.
PMID- 28419747
TI - A Randomized, Placebo- and Positive-Controlled, Single-Dose, Crossover Thorough
QT/QTc Study Assessing the Effect of Daprodustat on Cardiac Repolarization in
Healthy Subjects.
AB - Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical
studies for the treatment of anemia associated with chronic kidney disease. This
study was conducted to evaluate the effect of daprodustat on cardiac
repolarization and enrolled 55 healthy adult male (29) and female (26) subjects
who received single-dose 75 and 500 mg daprodustat, 400 mg moxifloxacin, and
placebo. Mean placebo-corrected change from baseline QT interval for daprodustat
showed no statistically significant increase. However, statistically significant
decreases in the DeltaDeltaQTcF were observed for both doses of daprodustat,
reaching a lowest value of -2.74 milliseconds for 75 mg and -5.93 milliseconds
for 500 mg daprodustat; this minor shortening effect is not considered clinically
significant. The moxifloxacin group showed a statistically significant increase
in the DeltaDeltaQTcF value, reaching a maximal increase of 11.47 milliseconds at
4 hours. Forty subjects (73%) reported at least 1 adverse event, with the highest
incidence with 500 mg daprodustat. This group had a higher incidence of
gastrointestinal adverse events compared to the other treatment groups. These
results suggest that 500 mg daprodustat was not well tolerated; however,
daprodustat at 75 mg was generally well tolerated. No new safety concerns were
identified in subjects who received 500 mg daprodustat.
PMID- 28419748
TI - The 'known' genetic potential for microbial communities to degrade organic
phosphorus is reduced in low-pH soils.
AB - In soil, bioavailable inorganic orthophosphate is found at low concentrations and
thus limits biological growth. To overcome this phosphorus scarcity, plants and
bacteria secrete numerous enzymes, namely acid and alkaline phosphatases, which
cleave orthophosphate from various organic phosphorus substrates. Using profile
hidden Markov modeling approaches, we investigated the abundance of various non
specific phosphatases, both acid and alkaline, in metagenomes retrieved from
soils with contrasting pH regimes. This analysis uncovered a marked reduction in
the abundance and diversity of various alkaline phosphatases in low-pH soils that
was not counterbalanced by an increase in acid phosphatases. Furthermore, it was
also discovered that only half of the bacterial strains from different phyla
deposited in the Integrated Microbial Genomes database harbor alkaline
phosphatases. Taken together, our data suggests that these 'phosphatase lacking'
isolates likely increase in low-pH soils and future research should ascertain how
these bacteria overcome phosphorus scarcity.
PMID- 28419749
TI - Novel 19 F-MRS beta-galactosidase reporter molecules incorporated nitrogen
mustard analogues.
AB - In this study, we propose a novel molecular platform-integrated fluorinated
antitumor nitrogen mustards for 19 F-MRS assay of beta-galactosidase (beta-gal)
activity. Following this idea, we have designed, synthesized, and characterized 2
fluoro-4-[bis(2'-chloroethyl)amino]phenyl beta-D-galactopyranoside 5, 2-fluoro-4
{bis[2'-O-(beta-D-galactopyranosyl)ethyl]amino}phenyl beta-D-galactopyranoside 8,
2-fluoro-4-{bis[[1"-(beta-D-galactopyranosyl)-1", 2", 3"-triazol-4"-yl]methyl]
amino}phenyl beta-D-galactopyranoside 14 and 2-fluoro-4-{bis[[1"-(beta-D
glucopyranosyl)-1", 2", 3"-triazol-4"-yl]methyl]amino}phenyl beta-D
galactopyranoside 15 through glycosylation and click reaction strategies, and
their structures were confirmed by NMR and HRMS or elemental analysis data. Among
them, 2-fluoro-4-[bis(2'-chloroethyl)amino]phenyl beta-D-galacto-pyranoside 5 was
found very sensitive to beta-gal (E801A) in PBS at 37 degrees C with big
DeltadeltaF response. Here, we demonstrated the feasibility of this platform for
assessing beta-gal activity in solution, and in vitro with lacZ-transfected human
MCF7 breast and PC3 prostate tumor cells, by the characterization of beta-gal
responsive 19 F-chemical shift changes DeltadeltaF and hydrolytic kinetics.
PMID- 28419750
TI - The effectiveness of virtual and augmented reality in health sciences and medical
anatomy.
AB - Although cadavers constitute the gold standard for teaching anatomy to medical
and health science students, there are substantial financial, ethical, and
supervisory constraints on their use. In addition, although anatomy remains one
of the fundamental areas of medical education, universities have decreased the
hours allocated to teaching gross anatomy in favor of applied clinical work. The
release of virtual (VR) and augmented reality (AR) devices allows learning to
occur through hands-on immersive experiences. The aim of this research was to
assess whether learning structural anatomy utilizing VR or AR is as effective as
tablet-based (TB) applications, and whether these modes allowed enhanced student
learning, engagement and performance. Participants (n = 59) were randomly
allocated to one of the three learning modes: VR, AR, or TB and completed a
lesson on skull anatomy, after which they completed an anatomical knowledge
assessment. Student perceptions of each learning mode and any adverse effects
experienced were recorded. No significant differences were found between mean
assessment scores in VR, AR, or TB. During the lessons however, VR participants
were more likely to exhibit adverse effects such as headaches (25% in VR P <
0.05), dizziness (40% in VR, P < 0.001), or blurred vision (35% in VR, P < 0.01).
Both VR and AR are as valuable for teaching anatomy as tablet devices, but also
promote intrinsic benefits such as increased learner immersion and engagement.
These outcomes show great promise for the effective use of virtual and augmented
reality as means to supplement lesson content in anatomical education. Anat Sci
Educ 10: 549-559. (c) 2017 American Association of Anatomists.
PMID- 28419751
TI - Clinical Characteristics of Fibromyalgia in a Chronic Pain Population.
AB - OBJECTIVE: To compare fibromyalgia (FM) characteristics among patients identified
in a community-based chronic pain cohort based on traditional International
Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of
patients identified using a novel predictive model. METHODS: This retrospective
study used data collected from July 1999 to February 17, 2015, in multiple
chronic pain clinics in the United States. Patients were assigned to the FM case
group based on specific inclusion criteria using ICD-9 codes or, separately, from
results of a novel FM predictive model that was developed using random forest and
logistic regression techniques. Propensity scoring (1:1) matched FM patients
(cases) to nonmalignant chronic pain patients without FM (controls). Patient
reported measures (eg, pain, fatigue, quality of sleep) and clinical
characteristics (ie, comorbidities, procedures, and regions of pain) were
outcomes for analysis. RESULTS: Nine ICD-9 clinical modification diagnoses had
odds ratios with large effect sizes (Cohen's d > 0.8), demonstrating the
magnitude of the difference between the FM and matched non-FM cohorts: chronic
pain syndrome, latex allergy, muscle spasm, fasciitis, cervicalgia, thoracic
pain, shoulder pain, arthritis, and cervical disorders (all P < 0.0001). Six
diagnoses were found to have a moderate effect size (Cohen's 0.5 < d > 0.8):
cystitis, cervical degeneration, anxiety, joint pain, lumbago, and cervical
radiculitis. CONCLUSIONS: The identification of multiple comorbidities,
diagnoses, and musculoskeletal procedures that were significantly associated with
FM may facilitate differentiation of FM patients from other conditions
characterized by chronic widespread pain. Predictive modeling may enhance
identification of FM patients who may otherwise go undiagnosed.
PMID- 28419752
TI - Surface orientation effects on bending properties of surgical mesh are
independent of tensile properties.
AB - INTRODUCTION: Current mechanical testing of surgical mesh focuses primarily on
tensile properties even though implanted devices are not subjected to pure
tensile loads. Our objective was to determine the flexural (bending) properties
of surgical mesh and determine if they correlate with mesh tensile properties.
METHODS: The flexural rigidity values of 11 different surgical mesh designs were
determined along three textile directions (machine, cross-machine, and 45 degrees
to machine; n = 5 for each) using ASTM D1388-14 while tracking surface
orientation. Tensile testing was also performed on the same specimens using ASTM
D882-12. Linear regressions were performed to compare mesh flexural rigidity to
mesh thickness, areal mass density, filament diameter, ultimate tensile strength,
and maximum extension. RESULTS: Of 33 mesh specimen groups, 30 had significant
differences in flexural rigidity values when comparing surface orientations (top
and bottom). Flexural rigidity and mesh tensile properties also varied with
textile direction (machine and cross-machine). There was no strong correlation
between the flexural and tensile properties, with mesh thickness having the best
overall correlation with flexural rigidity. CONCLUSIONS: Currently, surface
orientation is not indicated on marketed surgical mesh, and a single mesh may
behave differently depending on the direction of loading. The lack of correlation
between flexural stiffness and tensile properties indicates the need to examine
mesh bending stiffness to provide a more comprehensive understanding of surgical
mesh mechanical behaviors. Further investigation is needed to determine if these
flexural properties result in the surgical mesh behaving mechanically different
depending on implantation direction. (c) 2017 Wiley Periodicals, Inc. J Biomed
Mater Res Part B: Appl Biomater, 106B: 854-862, 2018.
PMID- 28419753
TI - Systematic Review of Gender Differences in Sepsis Management and Outcomes.
AB - PURPOSE: Contributors to disparities in sepsis management have been attributed to
genetic susceptibility, differences in clinical presentation, and healthcare
delivery. The influence of gender on survival or mortality of patients with
sepsis-related diagnoses is unclear. The purpose of the current study was to
systematically review published research to identify factors and outcomes
associated with sepsis management and outcomes based on gender differences.
METHODS: Covering a period from 2006 to 2016, a literature search was conducted
on four electronic data bases including the Cumulative Index to Nursing and
Allied Health Literature (CINAHL), EBSCO, MedlinePlus, and PubMed. Content
analysis of each article was performed independently by two authors. The
guidelines outlined in the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) Statement was the method used to assess the quality of
evidence of the articles in this review. FINDINGS: A full review was completed on
a total of 452 identified potentially relevant publications, and 7 publications
met inclusion criteria. The methodological approaches included prospective and
retrospective observational studies, and prospective and historical cohort
studies. The aim of these studies was to identify if gender differences exist
related to sepsis-related mortality, completion of Surviving Sepsis Campaign
resuscitation bundle elements, sepsis-related care processes, and sepsis-related
incidence and source. CONCLUSIONS: Clinical sepsis studies evaluating gender and
sepsis-related management and mortality are inconclusive and complex. Three
different outcomes exist: no difference, higher risk in females, or higher risk
in males. Further studies are needed to support the presence of gender
disparities on sepsis-related healthcare outcomes. CLINICAL RELEVANCE: Providers
should understand the importance of adhering to sepsis protocols and minimizing
treatment disparities including gender differences.
PMID- 28419754
TI - A field-based disparity analysis of new 1,2,5-oxadiazole derivatives endowed with
antiproliferative activity.
AB - A series of 1,2,5-oxadiazoles were synthesized as new potential antiproliferative
agents. The in vitro cytotoxic activity evaluation of title compounds through MTT
assay revealed that some of them showed significant activity against the HCT-116
cancer cell line. The field-based disparity analysis provided indications about
the electrostatic, hydrophobic, and shape features underlying the cytotoxicity,
suggesting that increasing the negative electrostatic field on the heterocyclic
core of the structure has positive effects on the activity. The structure
activity relationships (SAR) around a particular compound can be explained
allowing for a structural rationale for the differences in activity. The SAR
provided by this series of compounds can be exploited to carry out further lead
optimization.
PMID- 28419755
TI - A diagnostic algorithm for assessment of liver fibrosis by liver stiffness
measurement in patients with chronic hepatitis B.
AB - Steatosis could affect liver stiffness measurement in patients with nonalcoholic
fatty liver disease and chronic hepatitis C. In this study, we aimed to
investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)
infected patients and develop a diagnostic algorithm for prediction of liver
fibrosis by liver stiffness based on the controlled attenuation parameter. A
total of 488 HBV-infected patients who underwent clinical examination, Fibroscan
and liver biopsy were prospectively enrolled. The best liver stiffness
measurement (kPa) cut-offs for significant fibrosis (S>=3) and advanced fibrosis
(S>=4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter
cut-off for severe steatosis (>=30%) was 287 dB/m. Among patients with low-grade
fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in
subjects with severe steatosis or controlled attenuation parameter >=287 dB/m
compared with those without. Moreover, in subjects with low-grade fibrosis, a
higher rate of false-positive rate was observed in patients with severe steatosis
than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and
in patients with CAP>=287 dB/m compared with their counterpart (F0-F2: 23.7% vs
9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by
gamma-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of
0.17. In patients with GPR<0.17, similar results were observed. The presence of
steatosis may lead to overestimation of fibrosis assessed by liver stiffness
measurement in patient with chronic hepatitis B. A diagnostic algorithm for
assessing fibrosis using liver stiffness was developed by combining both
controlled attenuation parameter and GPR values.
PMID- 28419756
TI - Posterior ankle labral changes at MRI: A preliminary study.
AB - INTRODUCTION: The transverse ligament in the ankle joint has been described as a
labrum-like structure in a previous cadaveric study. The purpose of this study is
to assess the spectrum of abnormal changes related to this structure on
imaging/MRI, and correlate these findings with other ankle joint findings and
patient symptoms. METHOD: A retrospective observational review of 172 ankle MRI
scans was carried out independently by two fellowship trained musculoskeletal
Radiologists. Correlation between abnormal labral changes, other ankle joint
findings and patient symptomatology was performed. RESULTS: Abnormal labral
changes were seen in 26% of the MRI scans (n = 44/172) and included signal
change, contour abnormality with heterogeneous signal change, linear fluid filled
clefts, multidirectional fluid filled clefts, and a macerated labrum. There was a
statistically significant association between abnormal labral changes and the
presence of Stieda process/os trigonum (P = 0.001), talocrural joint
osteoarthritis (P = 0.0003), paralabral cysts (P = 0.0001), imaging features of
posterior impingement (P = 0.01), and both medial (P = 0.005) and lateral (P =
0.01) ankle ligament injuries. However, there was no statistically significant
association between abnormal labral changes and patient symptoms. CONCLUSION: The
posterior ankle labrum can develop a spectrum of abnormal MRI appearances in
patients with other ankle joint abnormalities. Although this study showed no
correlation between patients' symptoms and posterior ankle labral changes, larger
studies are needed to examine the biomechanical alterations that may arise from
these labral changes.
PMID- 28419757
TI - Social media and student engagement in anatomy education.
PMID- 28419758
TI - Provenance effect on carbon assimilation, photochemistry and leaf morphology in
Mediterranean Cistus species under chilling stress.
AB - The potential resilience of shrub species to environmental change deserves
attention in those areas threatened by climate change, such as the Mediterranean
Basin. We asked if leaves produced under different climate conditions through the
winter season to spring can highlight the leaf traits involved in determining
potential resilience of three Cistus spp. to changing environmental conditions
and to what extent intraspecific differences affect such a response. We analysed
carbon assimilation, maximum quantum efficiency of PSII photochemistry (Fv /Fm )
and leaf morphological control of the photosynthetic process in leaves formed
through the winter season into spring in C. creticus subsp. eriocephalus (CE), C.
salvifolius (CS) and C. monspeliensis (CM) grown from seed of different
provenances under common garden conditions. Intraspecific differences were found
in Fv /Fm for CE and CS. Carbon assimilation-related parameters were not affected
by provenance. Moreover, our analysis highlighted that the functional
relationships investigated can follow seasonal changes and revealed patterns
originating from species-specific differences in LMA arising during the
favourable period. Cistus spp. have great ability to modify the structure and
function of their leaves in the mid-term in order to cope with changing
environmental conditions. The Fv /Fm response to chilling reveals that
susceptibility to photoinhibition is a trait under selection in Cistus species.
Concerning carbon assimilation, differing ability to control stomatal opening was
highlighted between species. Moreover, seasonal changes of the functional
relationships investigated can have predictable consequences on species leaf
turnover strategies.
PMID- 28419760
TI - Bone marrow-derived stem/stromal cells and adipose tissue-derived stem/stromal
cells: Their comparative efficacies and synergistic effects.
AB - Mesenchymal stem cells (MSCs) are heterogeneous cell populations that serve as
reserves for tissue regeneration in the presence of disease or injury. Although
MSCs are found in various tissues, bone marrow-derived stem/stromal cells (BMSCs)
and adipose tissue-derived stem/stromal cells (ADSCs) have been most thoroughly
investigated. Furthermore, ADSCs have recently emerged as an attractive source of
MSCs due to their abundance and availability. BMSCs and ADSCs demonstrate similar
morphological characteristics, but their in vitro characteristics and
differentiation abilities appear to differ. In this review, the author summarizes
and compares current knowledge on BMSCs and ADSCs with particular emphasis on in
vitro expansion and osteogenic/angiogenic potential, and reviews knowledge of
their synergistic effects when co-applied. (c) 2017 Wiley Periodicals, Inc. J
Biomed Mater Res Part A: 105A: 2640-2648, 2017.
PMID- 28419761
TI - Pyoderma gangrenosum in Sjogren's syndrome and its successful treatment with
topical application of etanercept.
PMID- 28419759
TI - Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP
effector BerB.
AB - Knowledge about the molecular mechanisms that are involved in the regulation of
biofilm formation is essential for the development of biofilm-control measures.
It is well established that the nucleotide second messenger cyclic diguanosine
monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many
bacteria, but more knowledge about c-di-GMP effectors is needed. We provide
evidence that c-di-GMP, the alternative sigma factor RpoN (sigma54), and the
enhancer-binding protein BerB play a role in biofilm formation of Burkholderia
cenocepacia by regulating the production of a biofilm-stabilizing
exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates
RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive
transcriptional regulator. An increased level of the BerA protein in turn induces
the production of biofilm-stabilizing exopolysaccharide in response to high c-di
GMP levels. Our findings imply that the production of biofilm exopolysaccharide
in B. cenocepacia is regulated through a cascade involving two consecutive
transcription events that are both activated by c-di-GMP. This type of regulation
may allow tight control of the expenditure of cellular resources.
PMID- 28419762
TI - Hobnail variant of papillary thyroid carcinoma: A case with an unusual
presentation.
AB - Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases,
some of which are proven to be associated with aggressive clinical behavior such
as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is
recently described as a rare and aggressive variant of PTC. Herein, we are
reporting a case of HVPTC in a patient who presented with hemoptysis and an
intratracheal blood clot that was aspirated and submitted for cytopathological
examination. Cytomorphology displayed neoplastic cells with profound
micropapillary architecture, elongated nuclei, and prominent hobnail
configuration. Nuclear features of PTC such as pseudoinclusions, nuclear
overlapping, crowding, and grooves were readily identified. Subsequent total
thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC
is a rare locally aggressive subtype, which may present with metastasis from an
occult thyroid primary. HVPTC needs to be included in the differential diagnosis
of metastatic carcinoma with micropapillary architecture on fine needle
aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754
756. (c) 2017 Wiley Periodicals, Inc.
PMID- 28419763
TI - The effects of local cold application on fibromyalgia pain.
AB - AIM: This study was conducted to evaluate the effects of local cold application
on pain when applied to the trapezius muscles of patients with fibromyalgia.
METHOD: A one-group, pre-test/post-test, pre-experimental model was applied in
this study, which was conducted with 55 fibromyalgia patients who presented to a
rheumatology outpatient clinic. A 10-min cold application was administered to one
trapezius muscle of each patient. The participants' pain was evaluated, in total,
four times (before the cold application and 10 min, 1.5 h and 24 h after the cold
application). The visual analogue scale (VAS) for pain was used to collect data
for the study, and Friedman and Wilcoxon tests were used to assess the data.
RESULTS: The patients' pain mean score before (6.45, SD:1.27) the cold
applications was found to be significantly higher than the scores noted 10 min
(2.75, SD:1.73), 1.5 h (2.45, SD:1.29), and 24 h (3.36, SD:1.30) after the
application (P < 0.001). CONCLUSION: The study found that local cold applications
performed on the trapezius muscles of patients with fibromyalgia significantly
decreased their pain. With its discovery of a new method of pain control in
fibromyalgia patients, this study will significantly contribute to science and
will serve as a guide for pain management, especially in nursing practice.
Further studies to evaluate the maximum effect duration and effect mechanisms of
local cold applications to the trapezius muscles of FM patients are indicated.
PMID- 28419764
TI - Clinical application and verification of the TG13 diagnostic and severity grading
criteria for acute cholangitis: an international multicenter observational study.
AB - BACKGROUND: The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and
severity grading criteria for acute cholangitis. Subsequently updated in 2013,
the Tokyo Guidelines (TG13) have been widely adopted throughout the world as
global standard guidelines. We set out to verify the efficacy of these TG13
criteria in an international multicenter study. METHODS: We reviewed 6,063
patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan
over a 2-year period. The TG13 diagnostic and severity grading criteria were
retrospectively applied, and 30-day mortality was investigated. RESULTS: A
diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of
the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07
criteria. The 30-day mortality rates of patients with Grade III, Grade II, and
Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly
along with disease severity. The mortality rate in the 1,272 Grade II cases where
urgent or early biliary drainage was performed was 2.0% (n = 25), which was
significantly lower than that of 3.7% (n = 28) in the other 748 cases.
CONCLUSION: By using the TG13 diagnostic and severity grading criteria, more
patients with possible acute cholangitis can be diagnosed, and patients whose
prognosis can potentially be improved by early biliary drainage can be
identified. The TG13 criteria are appropriate and useful for clinical practice.
PMID- 28419766
TI - Microbial community function in the bleaching disease of the marine macroalgae
Delisea pulchra.
AB - Disease is increasingly viewed as a major factor impacting the health of both
natural and cultured populations of marine organisms, including macroalgae. The
red macroalga Delisea pulchra suffers from a bleaching disease resulting from
host stress and infection by opportunistic bacterial pathogens. However, how
pathogens cause the disease and how the entire macro algal-associated community
is involved in the process is unclear. Here, we perform a metagenomic analysis of
microbial communities associated with diseased and healthy D. pulchra across
multiple bleaching events. Analysis of reconstructed 16S rRNA gene sequences
showed that bacteria belonging to the families Rhodobacteraceae, Saprospiraceae
and Flavobacteriaceae, including bacteria previously implicated in algal
bleaching, to be enriched in diseased D. pulchra. Genes with predicted functions
related to chemotaxis, motility, oxidative stress response, vitamin biosynthesis
and nutrient acquisition were also prevalent in microbiomes of bleached algae,
which may have a role in pathogenicity. Reconstruction of genomes that were
abundant on bleached samples revealed that no single organism contains all
bleaching-enriched functional genes. This observation indicates that potential
virulence traits are distributed across multiple bacteria and that the disease in
D. pulchra may result from a consortium of opportunistic pathogens, analogous to
dysbiotic or polymicrobial diseases.
PMID- 28419765
TI - Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at
Enabling Safer and Earlier Translation of Biological Insights Into Human Testing.
PMID- 28419767
TI - Four New Diterpene Glucosides from Perovskia atriplicifolia.
AB - Four new diterpene glucosides, namely perovskiaditerpenosides A - D (1 - 4), were
isolated from the BuOH extract of Perovskia atriplicifolia. Their structures were
well elucidated by chemical methods and comprehensive spectroscopic analyses
including MS, IR, and NMR (1D and 2D). The newly isolated compounds were screened
for their cytotoxic activity against HepG2, NB4, HeLa, K562, MCF7, PC3, and HL60.
The obtained results indicated that the new compounds possessed considerable
cytotoxic activity.
PMID- 28419768
TI - Pneumatosis intestinalis related to jejunal feeding post-pancreaticoduodenectomy.
PMID- 28419769
TI - Nurse practitioner perceptions of barriers and facilitators in providing health
care for deaf American Sign Language users: A qualitative socio-ecological
approach.
AB - BACKGROUND AND PURPOSE: Nurse practitioners (NPs), as well as all healthcare
clinicians, have a legal and ethical responsibility to provide health care for
deaf American Sign Language (ASL) users equal to that of other patients,
including effective communication, autonomy, and confidentiality. However, very
little is known about the feasibility to provide equitable health care. The
purpose of this study was to examine NP perceptions of barriers and facilitators
in providing health care for deaf ASL users. DATA SOURCES: Semistructured
interviews in a qualitative design using a socio-ecological model (SEM).
CONCLUSIONS: Barriers were identified at all levels of the SEM. NPs preferred
interpreters to facilitate the visit, but were unaware of their role in assuring
effective communication is achieved. A professional sign language interpreter was
considered a last resort when all other means of communication failed. Gesturing,
note-writing, lip-reading, and use of a familial interpreter were all considered
facilitators. IMPLICATIONS FOR PRACTICE: Interventions are needed at all levels
of the SEM. Resources are needed to provide awareness of deaf communication
issues and legal requirements for caring for deaf signers for practicing and
student NPs. Protocols need to be developed and present in all healthcare
facilities for hiring interpreters as well as quick access to contact information
for these interpreters.
PMID- 28419770
TI - Pilot survey of the health of Massachusetts dentists.
AB - AIM: Dentistry is a career that is very rewarding because of the direct
opportunity to deliver essential health services to patients in need. Dentistry
is also very demanding; mentally, physically, and even emotionally. Little is
known about the health of dentists and how it compares to the health of the
general population. The aim of the present study was to report on the general
health and health practices of dentists in Massachusetts. METHODS: A medical
health and health practices survey was developed from the Delaware Valley
Community Health Center and customized. The surveys contained 36 questions
relating to demographics, general health, and health practices. RESULTS: A total
of 399 dentists completed the survey. Of those who responded to the survey, 78.2%
were males, 32.6% were 56-65 years of age, 23.1% were 66-75 years of age, and
21.6% were 46-55 years of age. CONCLUSION: This pilot study highlights several
health issues where dentists seem to have a lower incidence than the general
population: asthma, depression, diabetes, hearing loss, obesity, smoking, sleep
apnea, and thyroid disease. However, there are some health issues where dentists
have a higher incidence than the general population: taking at least one
prescription medication, gastroesophageal reflux disease, some form of cancer,
back pain, neck pain, headache, osteoarthritis, rheumatic arthritis, psoriatic
arthritis, and alcohol abuse.
PMID- 28419771
TI - Aspects of carotid structure and function in health and different stages of
chronic kidney disease.
AB - INTRODUCTION: Arterial remodelling and stiffening have been demonstrated in end
stage renal disease (ESRD). The presence of vascular alterations in earlier-stage
chronic kidney disease (CKD) is less studied. We evaluated vascular structure and
function in mild-to-moderate CKD (stages 2-3) compared with healthy subjects and
advanced CKD (stages 4-5). METHODS: Carotid ultrasound was performed in 103 non
dialysis CKD patients and 54 healthy controls. Carotid intima-media thickness
(CIMT) and common carotid artery (CCA) diameter were measured. Strain, stiffness
and the pressure-strain elastic modulus (Ep ) of the right CCA were calculated.
RESULTS: There was no significant difference in CCA diameter between CKD 2-3 and
controls. The CCA diameter was larger in CKD 4-5 compared with CKD 2-3 and
controls (CKD 4-5, 6.50 +/- 0.79 mm versus CKD 2-3, 6.08 +/- 0.56 mm, P = 0.003;
and versus controls 5.97 +/- 0.53 mm, P<0.001). However, after adjustments, the
difference in CCA diameter was valid only for older ages and also dependent on
systolic blood pressure (SBP). There were no significant differences in CIMT,
strain or stiffness between the groups, but Ep was higher in CKD 4-5 compared
with controls (P = 0.006). CONCLUSION: In mild-to-moderate CKD, there were no
significant differences in carotid artery structure or function compared with
healthy subjects. Only patients with advanced CKD and older ages showed signs of
arterial remodelling. Our study indicates that vascular alterations occur in
advanced CKD, with SBP and age as important contributing factors.
PMID- 28419772
TI - Visual memory uniquely predicts anhedonia in schizophrenia but not bipolar
disorder.
AB - OBJECTIVE: Deficits in memory have been suggested as an influential mechanism of
anhedonia, because while pleasant experiences may be enjoyed in-the-moment, the
cognitive processes involved in reporting anticipated or remembered enjoyable
experiences is thought to be impaired. This study will determine whether any
aspects of memory, including visual memory, verbal memory or working memory, are
significantly predictive of anhedonia in a sample of schizophrenia, psychotic
bipolar disorder and healthy controls. METHODS: The study included 38 individuals
with schizophrenia, 19 individuals with bipolar disorder with psychosis, and 43
age-matched healthy controls. All participants completed a self-report social and
physical anhedonia questionnaire along with a cognitive screening battery, which
assessed the domains of attention/vigilance, working memory, verbal learning,
visual learning, and reasoning and problem-solving. RESULTS: Anhedonia scores
were regressed onto domain scores to determine which areas of cognition uniquely
predicted level of anhedonia in each group. For the schizophrenia group, physical
anhedonia was significantly predicted by worse visual memory performance. The
regression models did not find significant cognitive predictors of physical or
social anhedonia in the bipolar disorder or control groups. CONCLUSIONS: This
study found a significant relationship between visual memory and physical
anhedonia in schizophrenia patients that was not present in a sample of psychotic
bipolar patients or healthy controls, adding to an accumulating body of evidence
that visual memory is related to anhedonia in schizophrenia. This relationship
may be explained by underlying abnormalities in the orbitofrontal cortex in
schizophrenia.
PMID- 28419773
TI - Non-invasive follicular neoplasm with papillary like nuclear features (NIFTP): If
it ain't broke, don't fix it. The cytopathologist's dilemma.
PMID- 28419774
TI - Double trouble: Concomitant infection of esophagus by Herpes and Candida in
diabetic, non HIV patients-Report of two cases.
PMID- 28419775
TI - Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum
Disorder.
AB - Autism is a complex genetic disorder where both de-novo and inherited genetics
factors play a role. Next generation sequencing approaches have been extensively
used to identify rare variants associated with autism. To date, all such studies
were focused on nuclear genome; thereby leaving the role of mitochondrial DNA
(mtDNA) variation in autism unexplored. Recently, analytical tools have been
developed to evaluate mtDNA in whole-exome data. We have analyzed the mtDNA
sequence derived from whole-exome sequencing in 10 multiplex families. In one of
the families we have identified two variants of interest in MT-ND5 gene that were
previously determined to impair mitochondrial function. In addition in a second
family we have identified two VOIs; mtDNA variant in MT-ATP6 and nuclear DNA
variant in NDUFS4, where both VOIs are within mitochondrial Respiratory Chain
Complex. Our findings provide further support for the role of mitochondria in ASD
and confirm that whole-exome sequencing allows for analysis of mtDNA, which sets
a stage for further comprehensive genetic investigations of the role of
mitochondria in autism. Autism Res 2017, 10: 1338-1343. (c) 2017 International
Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28419777
TI - MicroRNAs as biomarkers for psychiatric disorders with a focus on autism spectrum
disorder: Current progress in genetic association studies, expression profiling,
and translational research.
AB - MicroRNAs (miRNAs) are a group of small noncoding RNA molecules, 18-25
nucleotides in length, which can negatively regulate gene expression at the post
transcriptional level by binding to messenger RNAs. About half of all identified
miRNAs in humans are expressed in the brain and display regulatory functions
important for many biological processes related to the development of the central
nervous system (CNS). Disruptions in miRNA biogenesis and miRNA-target
interaction have been related to CNS diseases, including psychiatric disorders.
In this review, we focus on the role of miRNAs in autism spectrum disorder (ASD)
and summarize recent findings about ASD-associated genetic variants in miRNA
genes, in miRNA biogenesis genes, and miRNA targets. We discuss deregulation of
miRNA expression in ASD and functional validation of ASD-related miRNAs in animal
models. Including miRNAs in studies of ASD will contribute to our understanding
of its etiology and pathogenesis and facilitate the discrimination between
different disease subgroups. Autism Res 2017. (c) 2017 International Society for
Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1184-1203. (c) 2017
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 28419776
TI - The involuntary nature of binge drinking: goal directedness and awareness of
intention.
AB - Binge drinking represents a public health issue and is a known risk factor in the
development of alcohol use disorders. Previous studies have shown behavioural as
well as neuroanatomical alterations associated with binge drinking. Here, we
address the question of the automaticity or involuntary nature of the behaviour
by assessing goal-directed behaviour and intentionality. In this study, we used a
computational two-step task, designed to discern between model-based/goal
directed and model-free/habitual behaviours, and the classic Libet clock task, to
study intention awareness, in a sample of 31 severe binge drinkers (BD) and 35
matched healthy volunteers. We observed that BD had impaired goal-directed
behaviour in the two-step task compared with healthy volunteers. In the Libet
clock task, BD showed delayed intention awareness. Further, we demonstrated that
alcohol use severity, as reflected by the alcohol use disorders identification
test, correlated with decreased conscious awareness of volitional intention in
BD, although it was unrelated to performance on the two-step task. However, the
time elapsed since the last drinking binge influenced the model-free scores, with
BD showing less habitual behaviour after longer abstinence. Our findings suggest
that the implementation of goal-directed strategies and the awareness of
volitional intention are affected in current heavy alcohol users. However, the
modulation of these impairments by alcohol use severity and abstinence suggests a
state effect of alcohol use in these measures and that top-down volitional
control might be ameliorated with alcohol use cessation.
PMID- 28419778
TI - Single- and Multiple-Dose Pharmacokinetics of Once-Daily Formulations of
Raltegravir.
AB - A new once-daily formulation of raltegravir, an integrase strand transfer
inhibitor indicated in combination with other antiretroviral drugs for the
treatment of human immunodeficiency virus-1 infection, is under development.
Single-dose and steady-state pharmacokinetics of 1200 mg for 2 formulations of
raltegravir were characterized in 2 open-label phase 1 studies in healthy male
and female subjects aged 18 to 55 years. The new raltegravir 600-mg formulation
had a higher relative bioavailability compared with the 400-mg tablets. Once
absorbed, both 3 * 400-mg and 2 * 600-mg dosage forms of raltegravir exhibited
similar systemic pharmacokinetics; in dictating bioavailability, differences were
from increased absorption that was the result of improved in vivo
disintegration/dissolution. Food had a smaller effect on the pharmacokinetics of
raltegravir when given as 2 * 600-mg formulation (42% vs 73% decrease in AUC0
last ). Steady state was generally reached in 2 days, with little to no
accumulation with multiple-dose administration. Raltegravir 1200 mg was found to
exhibit pharmacokinetic properties amenable for once-daily dosing and was
generally well tolerated in healthy subjects after single and multiple doses. The
new formulation improved the bioavailability of this Biopharmaceutics
Classification System class II compound.
PMID- 28419779
TI - Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan
collaborative study for acute cholecystitis.
AB - BACKGROUND: The collaborative multicenter retrospective study of acute
cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was
evaluation of the clinical value of TG13 severity grading for AC. METHOD: The
study was designed as an international multicenter retrospective study of AC from
2011 to 2013. Based on the data, we investigated the TG13 severity grading by
analyzing the correlations between grade and prognosis, surgical procedures,
histopathology, and organ dysfunction and prognosis. RESULTS: An investigation
revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade
II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher
than lower grades (P < 0.001). The greater the number of organ dysfunction, the
higher the mortality rate (P < 0.001). However, the mortality rate varied
depending on the number of organ dysfunction (3.1-25%). With respect to the
surgical procedures, laparoscopic cholecystectomy was performed for Grade I
patients (P < 0.001), and the higher the grade, the more likely open surgery
would be selected (P < 0.001). CONCLUSION: TG13 severity grading criteria for AC
are providing great benefits in actual clinical settings. From this study, the
position of each severity grade was obviously confirmed.
PMID- 28419781
TI - Evaluation of stability of stereotactic space defined by cone-beam CT for the
Leksell Gamma Knife Icon.
AB - The Gamma Knife Icon comes with an integrated cone-beam CT (CBCT) for image
guided stereotactic treatment deliveries. The CBCT can be used for defining the
Leksell stereotactic space using imaging without the need for the traditional
invasive frame system, and this allows also for frameless thermoplastic mask
stereotactic treatments (single or fractionated) with the Gamma Knife unit. In
this study, we used an in-house built marker tool to evaluate the stability of
the CBCT-based stereotactic space and its agreement with the standard frame-based
stereotactic space. We imaged the tool with a CT indicator box using our CT
simulator at the beginning, middle, and end of the study period (6 weeks) for
determining the frame-based stereotactic space. The tool was also scanned with
the Icon's CBCT on a daily basis throughout the study period, and the CBCT images
were used for determining the CBCT-based stereotactic space. The coordinates of
each marker were determined in each CT and CBCT scan using the Leksell GammaPlan
treatment planning software. The magnitudes of vector difference between the
means of each marker in frame-based and CBCT-based stereotactic space ranged from
0.21 to 0.33 mm, indicating good agreement of CBCT-based and frame-based
stereotactic space definition. Scanning 4-month later showed good prolonged
stability of the CBCT-based stereotactic space definition.
PMID- 28419782
TI - Natural resource landscapes of a marine bacterium reveal distinct fitness
determining genes across the genome.
AB - Heterotrophic bacteria exploit diverse microhabitats in the ocean, from particles
to transient gradients. Yet the degree to which genes and pathways can contribute
to an organism's fitness on such complex and variable natural resource landscapes
remains poorly understood. Here, we determine the gene-by-gene fitness of a
generalist saprophytic marine bacterium (Vibrio sp. F13 9CS106) on complex
resources derived from its natural habitats - copepods (Apocyclops royi) and
brown algae (Fucus vesiculosus) - and as reference substrates, glucose and the
polysaccharide alginate, derived from brown algal cell walls. We find that
resource complexity strongly buffers fitness costs of mutations, and that
anabolic rather than catabolic pathways are more stringently required, likely due
to functional redundancy in the latter. Moreover, while carbohydrate-rich algae
requires several synthesis pathways, protein-rich Apocyclops does not, suggesting
this ancestral habitat for Vibrios is a replete medium with metabolically
redundant substrates. We also identify a candidate fitness trade-off for algal
colonization: deletion of mshA increases mutant fitness. Our results demonstrate
that gene fitness depends on habitat composition, and suggest that this
generalist uses distinct resources in different natural habitats. The results
further indicate that substrate replete conditions may lead to relatively relaxed
selection on catabolic genes.
PMID- 28419783
TI - High occurrence of Bathyarchaeota (MCG) in the deep-sea sediments of South China
Sea quantified using newly designed PCR primers.
AB - The archaeal phylum Bathyarchaeota, which is composed of a large number of
diverse lineages, is widespread and abundant in marine sediments. Environmental
factors that control the distribution, abundance and evolution of this largely
diversified archaeal phylum are currently unclear. In this study, a new pair of
specific primers that target the major marine subgroups of bathyarchaeotal 16S
rRNA genes was designed and evaluated to investigate the distribution and
abundance of Bathyarchaeota in marine sediments. The abundance of Bathyarchaeota
along two sediment cores from the deep-sea sediments of South China Sea (SCS,
each from the Dongsha and Shenhu area) was determined. A strong correlation was
found between the bathyarchaeotal abundance and the content of total organic
carbon (TOC), suggesting an important role of Bathyarchaeota in organic matter
remineralisation in the sediments of SCS. Furthermore, diversity analysis
revealed that subgroups Bathy-2, Bathy-8 and Bathy-10 were dominant
bathyarchaeotal members of the deep-sea sediments in the SCS. Bathy-8 was found
predominantly within the reducing and deeper sediment layers, while Bathy-10
occurred preferentially in the oxidizing and shallower sediment layers. Our study
lays a foundation for the further understanding of the ecological functions and
niche differentiation of the important but not well-understood sedimentary
archaeal group.
PMID- 28419784
TI - Four-Extremity Neurostimulation Using Two Cervical Octapolar Leads and High
Frequency of 10 kHz.
AB - OBJECTIVES AND METHODS: A few published reports describe successful clinical use
of low-frequency spinal cord stimulation (SCS) in the cervical spine resulting in
bilateral upper and lower extremity pain relief. A major side-effect when using
this modality of SCS is the uneven intensity of paresthesias, which are
frequently excessive in upper extremities while attempting to achieve optimal
paresthesia coverage in all 4 extremities. RESULTS AND CONCLUSIONS: Here we
describe a successful case of high-frequency SCS at 10 kHz where profound control
of neuropathic pain of all 4 extremities was achieved without the complication of
paresthesias. Discussed are future implications of such therapy.
PMID- 28419785
TI - Internal noise estimates correlate with autistic traits.
AB - Previous neuroimaging research has reported increased internal (neural) noise in
sensory systems of autistic individuals. However, it is unclear if this
difference has behavioural or perceptual consequences, as previous attempts at
measuring internal noise in ASD psychophysically have been indirect. Here, we use
a "gold standard" psychophysical double-pass paradigm to investigate the
relationship between internal noise and autistic traits in the neurotypical
population (n = 43). We measured internal noise in three tasks (contrast
perception, facial expression intensity perception, and number summation) to
estimate a global internal noise factor using principal components analysis. This
global internal noise was positively correlated with autistic traits (rs = 0.32,
P = 0.035). This suggests that increased internal noise is associated with the
ASD phenotype even in subclinical populations. The finding is discussed in
relation to the neural and genetic basis of internal noise in ASD. Autism Res
2017, 10: 1384-1391. (c) 2017 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 28419786
TI - Toward the rational design of macrolide antibiotics to combat resistance.
AB - Macrolides, one of the most prescribed classes of antibiotics, bind in the
bacterial ribosome's polypeptide exit tunnel and inhibit translation. However,
mutations and other ribosomal modifications, especially to the base A2058 of the
23S rRNA, have led to a growing resistance problem. Here, we have used molecular
dynamics simulations to study the macrolides erythromycin and azithromycin in
wild-type, A2058G-mutated, and singly or doubly A2058-methylated Escherichia coli
ribosomes. We find that the ribosomal modifications result in less favorable
interactions between the base 2058 and the desosamine sugar of the macrolides, as
well as greater displacement of the macrolides from their crystal structure
position, illuminating the causes of resistance. We have also examined four
azithromycin derivatives containing aromatic indole-analog moieties, which were
previously designed based on simulations of the stalling peptide SecM in the
ribosome. Surprisingly, we found that the studied moieties could adopt very
different geometries when interacting with a key base in the tunnel, A751,
possibly explaining their distinct activities. Based on our simulations, we
propose modifications to the indole-analog moieties that should increase their
interactions with A751 and, consequently, enhance the potency of future
azithromycin derivatives.
PMID- 28419787
TI - Heisenberg strikes again.
AB - Systematic randomized clinical outcome data in BVS has largely been reported in
straightforward lesions, and BVS performance in more complex anatomy is not well
defined In this study, OCT-analysis of imaging outcomes in lesions with variable
degrees of calcification demonstrated similar acute performance between second
generation DES and BVS Open questions as to the unintended effect of OCT-guidance
on the results of the study as well as the longer-term clinical outcomes in these
lesions remain.
PMID- 28419788
TI - The Italian stallions of CLI "value care" delivery.
AB - Critical Limb ischemia with long segment occlusive disease typically reserved for
surgery can be treated with a high degree of success in expert centers via an
endovascular approach Nitinol woven stents appear to have high patency with
proper deployment in all PAD groups Increased early expense that is associated
with decreased re-intervention can be cost effective.
PMID- 28419789
TI - Overlapping bioresorbable scaffolds seems safe for now.
AB - Overlapping permanent scaffolds carries a long-term risk of target vessel failure
due to late malapposition and the development of neoatherosclerosis. Potentially,
overlapping bioresorbable scaffold (BRS) may lead to lower long-term risk. The
GHOST-EU registry reported similar short- and mid-term risks in patients with and
without BRS overlap. Larger size studies with longer follow-up are needed to
confirm the safety of BRS overlap.
PMID- 28419790
TI - The many radial access learning curves.
AB - The radial approach to endovascular procedures has a series of learning curves:
diagnostic heart catheterization, low-risk settings and "straightforward"
percutaneous coronary intervention, high-risk settings, and complex coronary
intervention, and peripheral vascular angiography and intervention. For
diagnostic and low-risk interventional procedures, incremental improvements in
technical success and safety are observed in the initial 200 procedures for most
operators compared to highly experienced operators. Formal didactic training and
ongoing support/review from an experienced radial operator(s) may expedite
surmounting the series of radial learning curves while maintaining optimal
procedural success and safety. Advances in technology and understanding will
require the most experienced radial operators to continually embrace their next
learning curve.
PMID- 28419791
TI - The role of rotational atherectomy in contemporary chronic total occlusion
percutaneous coronary intervention.
AB - Rotational atherectomy is performed infrequently (~3.5%) during chronic total
occlusion (CTO) percutaneous coronary intervention (PCI) for two indications:
treatment of balloon uncrossable and balloon undilatable lesions. Use of
rotational atherectomy in CTO PCI was associated with high success and acceptable
complication rates. Rotational atherectomy remains a "must have" device for
interventional cardiologists performing complex PCI.
PMID- 28419792
TI - Breaking the code: What is the best post-PCI MI definition?
AB - Various definitions of post-PCI MI have been recommended by different
professional societies and studies. This present study suggests that the troponin
based 3rd universal definition of post-PCI MI has prognostic value for recurrent
MI but not mortality alone, unlike the CK-MB based SCAI definition. Absent a
consensus on the best definition, clinical trials should report outcomes based on
multiple definitions of post-PCI MI.
PMID- 28419793
TI - Impact of emergency department discharge stream short stay unit performance and
hospital bed occupancy rates on access and patient flowmeasures: A single site
study.
AB - OBJECTIVE: The ED discharge stream short stay units (EDSSUs) aim to facilitate
patient flows through EDs. We investigate the relationship between EDSSU census
and hospital bed occupancy rates (BORs) on National Emergency Access Target
(NEAT) performance and did-not-wait (DNW) rates at a tertiary metropolitan adult
ED in Sydney, Australia. METHODS: We collated data for all ED presentations
between 1 January 2012 and 31 December 2014. Daily ED, EDSSU census and ED
accessible hospital BORs were tabulated with daily ED NEAT performance and DNW
rates. Non-parametric regression analyses was conducted on cohorts of
appropriate, inappropriate, successful and failed EDSSU admissions based on local
admission policies and BOR for NEAT and DNW outcomes. RESULTS: Among all
presentations (n = 192 506) during the study period, 43.8% of patients were
admitted in hospital including 10.4% for EDSSU (n = 20 081). Analyses reveal
modest positive correlation of EDSSU admissions with NEAT performance (tau =
0.35, P < 0.001) and weak negative correlation with DNW rates (tau = -0.29, P <
0.001). These associations were more pronounced on days when BOR >100% (tau =
0.39 and tau = -0.36, P < 0.001). BOR of >100% were associated with reduced EDSSU
admits, NEAT performance and increased DNW rates (P < 0.001). Appropriate EDSSU
admissions had shorter EDSSU length of stay than inappropriate EDSSU admissions
(350 vs 557 min, median difference -158 min, P < 0.001). CONCLUSION: Appropriate
use of EDSSU provides effective conduit for ongoing patients' management beyond
mandated timelines. Health systems should focus on reducing hospital BORs to
mitigate exclusive ED pressure to deliver NEAT performance targets.
PMID- 28419794
TI - [Healthy workplaces: a goal or a long-distance run?]
PMID- 28419795
TI - [Is it possible to improve the preventive usefulness of workers' health
surveillance in the current regulatory framework?]
AB - OBJECTIVE: In Spain, the limited preventive usefulness of health surveillance is
determined by the indiscriminate use of nonspecific "generic" health examinations
aimed at producing a "fitness for work list", presumably allowing companies to
comply with health and safety regulations. This study aimed to produce a
technical interpretation of the Spanish Prevention of Risks at Work Act and
propose a new conceptual framework to favour greater preventive usefulness of
health surveillance within the current regulatory framework. METHODS: Using
qualitative techniques of content analysis, the text of the Law was studied, the
key concepts that impeded the fulfilment of the preventive objectives of health
surveillance were identified, and a technical interpretation adjusted to
regulations was made in order to propose a new conceptual framework RESULTS: This
conceptual framework would include: clearly differentiating health surveillance
from health examinations (one of its instruments) and from fitness for work
evaluations (an independent concept in itself); restricting mandatory health
surveillance to situations in which it is "imperative" to carry it out because of
the existence of a substantial risk to workers or third parties, including
potentially vulnerable workers; and communicating the results of health
surveillance through preventive recommendations to the company, reserving fitness
for duty certificates -always based on clear, pre-established and justified
criteria in relation to risk- for mandatory surveillance. CONCLUSIONS: The
proposed new conceptual framework falls within the scope of the Spanish
Prevention of Risks at Work Act, and its implementation could contribute to
improving the preventive usefulness of health surveillance without the need to
reform the legislation.
PMID- 28419796
TI - [Third working conditions and health survey in Navarre, Spain: main findings].
AB - OBJECTIVE: To describe health problems and working conditions perceived by
workers of Navarra, Spain. METHODS: Conduct of the Third Survey of Working
Conditions and Health in Navarre. We administered the Seventh Spanish National
Survey of Working Conditions questionnaire by personal interviews conducted in
the workers' homes between October 2014 and December 2014, and using a three
stage stratified sampling approach, by economic activity, work establishment size
and gender. A total of 2744 interviews were completed, with a confidence level of
95.5% and P=Q, error +/- 1.99. The analysis was weighted by the sampling
variables. The results were summarized as percentages for qualitative variables
and point estimates for quantitative variables. RESULTS: Among the postivie
findings, 85% of respondents were well informed of job risks, 68% had access to a
health and safety representative, 50% underwent risk assessments and 60% received
periodic medical examinations. Among the notable self-reported occupational risk
factors were exposure to loud noise (16%), chemicals (33%), accident-prone
situations (76%), repetitive movements (62%), awkward postures (41%) and
biological agents (11%). Issues of concern include a high percentage of overtime
work (44% of men and 39% of women), feelings of being overworked (30.6% and
29.4%, respectively) and exposure to abusive behaviors (11.7% for verbal abuse),
especially among women, healthcare workers and teachers. The most prevalent
health problems were musculoskeletal (49% reporting back pain) and issues related
to work stress (20%). CONCLUSIONS: The current working conditions in Navarre
feature improved preventive services, persistence of traditional occupational
risk factors and emergence of new issues such as violence and work stressors.
PMID- 28419797
TI - [Alcohol consumption prevalence in civil servants].
AB - Alcohol consumption is a concern for its effects on health and repercussions on
the work environment. The objective of this study was to estimate the prevalence
of alcohol consumption among civil servants and to examine its association with
sociodemographic and occupational variables. A cross-sectional study was
conducted among 1180 workers from January to November 2011. The prevalence of
alcohol consumption was measured in ABV (alcohol by volume) units, and examined
by sociodemographic and occupational variables (sex, education level, type of
work and social class). Overall, 81.78%of the study population consumed alcohol;
most were men, with moderate-severe consumption levels. Alcohol consumption was
related to low education level, social class, and manual work. These results
indicate the need for occupational health services to implement preventive
actions at the workplace.
PMID- 28419798
TI - PVLOO-Based Training Set Selection Improves the External Predictability of
QSAR/QSPR Models.
AB - In QSAR/QSPR modeling, the indispensable way to validate the predictability of a
model is to perform its statistical external validation. It is common that a
division algorithm should be used to select training sets from chemical compound
libraries or collections prior to external validations. In this study, a division
method based on the posterior variance of leave-one-out cross-validation (PVLOO)
of the Gaussian process (GP) has been developed with the goal of producing more
predictive models. Four structurally diverse data sets of good quality are
collected from the literature and then redeveloped and validated on the basis of
training set selection methods, namely, four kinds of PVLOO-based training set
selection methods with three types of covariance functions (squared exponential,
rational quadratic, and neural network covariance functions), the Kennard-Stone
algorithm, and random division. The root mean squared error (RMSE) of external
validation reported for each model serves as a basis for the final comparison.
The results of this study indicate that the training sets with higher values of
PVLOO have statistically better external predictability than the training sets
generated from other division methods discussed here. These findings could be
explained by proposing that the PVLOO value of GP could indicate the mechanism
diversity of a specific compound in QSAR/QSPR data sets.
PMID- 28419799
TI - Synthesis of Protected 3-Deoxy-3-fluoro- and 4-Deoxy-4-fluoro-d
galactopyranosides from Levoglucosan.
AB - Fluorinated carbohydrates are invaluable tools to study various biochemical
processes. Herein, we describe a new strategy to access orthogonally protected 3
deoxy-3-fluorogalactopyranose and acetylated 4-deoxy-4-fluorogalactopyranose.
Starting from inexpensive levoglucosan, most reactions were performed on a gram
scale and allowed excellent regio- and stereocontrol with a minimal use of
protection/deprotection cycles. Hence, we developed practical alternatives to the
decade-long reported method to access both 3-deoxy-3-fluoro- and 4-deoxy-4
fluorogalactopyranose.
PMID- 28419800
TI - pH Reversible Encapsulation of Oppositely Charged Colloids Mediated by
Polyelectrolytes.
AB - We report the first example of reversible encapsulation of micron-sized particles
by oppositely charged submicron smaller colloids. The reversibility of this
encapsulation process is regulated by pH-responsive poly(acrylic acid) (PAA)
present in solution. The competitive adsorption between the small colloids and
the poly(acrylic acid) on the surface of the large colloids plays a key role in
the encapsulation behavior of the system. pH offers an experimental knob to tune
the electrostatic interactions between the two oppositely charged particle
species via regulation of the charge density of the poly(acrylic acid). This
results in an increased surface coverage of the large colloids by the smaller
colloids when decreasing pH. Furthermore, the poly(acrylic acid) also acts as a
steric barrier limiting the strength of the attractive forces between the
oppositely charged particle species, thereby enabling detachment of the smaller
colloids. Finally, based on the pH tunability of the encapsulation behavior and
the ability of the small colloids to detach, reversible encapsulation is achieved
by cycling pH in the presence of the PAA polyelectrolytes. The role of
polyelectrolytes revealed in this work provides a new and facile strategy to
control heteroaggregation behavior between oppositely charged colloids, paving
the way to prepare sophisticated hierarchical assemblies.
PMID- 28419801
TI - On-Surface Pseudo-High-Dilution Synthesis of Macrocycles: Principle and
Mechanism.
AB - Macrocycles have attracted much attention due to their specific "endless"
topology, which results in extraordinary properties compared to related linear
(open-chain) molecules. However, challenges still remain in their controlled
synthesis with well-defined constitution and geometry. Here, we report the
successful application of the (pseudo-)high-dilution method to the conditions of
on-surface synthesis in ultrahigh vacuum. This approach leads to high yields (up
to 84%) of cyclic hyperbenzene ([18]-honeycombene) via an Ullmann-type reaction
from 4,4"-dibromo-meta-terphenyl (DMTP) as precursor on a Ag(111) surface. The
mechanism of macrocycle formation was explored in detail using scanning tunneling
microscopy and X-ray photoemission spectroscopy. We propose that the dominant
pathway for hyperbenzene (MTP)6 formation is the stepwise desilverization of an
organometallic (MTP-Ag)6 macrocycle, which forms via cyclization of (MTP-Ag)6
chains under pseudo-high-dilution conditions. The high probability of cyclization
on the stage of the organometallic phase results from the reversibility of the C
Ag bond. The case is different from that in solution, in which cyclization
typically occurs on the stage of a covalently bonded open-chain precursor. This
difference in the cyclization mechanism on a surface compared to that in solution
stems mainly from the 2D confinement exerted by the surface template, which
hinders the flipping of chain segments necessary for cyclization.
PMID- 28419802
TI - Programming Post-Translational Control over the Metabolic Labeling of Cellular
Proteins with a Noncanonical Amino Acid.
AB - Transcriptional control can be used to program cells to label proteins with
noncanonical amino acids by regulating the expression of orthogonal aminoacyl
tRNA synthetases (aaRSs). However, we cannot yet program cells to control
labeling in response to aaRS and ligand binding. To identify aaRSs whose
activities can be regulated by interactions with ligands, we used a combinatorial
approach to discover fragmented variants of Escherichia coli methionyl tRNA
synthetase (MetRS) that require fusion to associating proteins for maximal
activity. We found that these split proteins could be leveraged to create ligand
dependent MetRS using two approaches. When a pair of MetRS fragments was fused to
FKBP12 and the FKBP-rapamycin binding domain (FRB) of mTOR and mutations were
introduced that direct substrate specificity toward azidonorleucine (Anl), Anl
metabolic labeling was significantly enhanced in growth medium containing
rapamycin, which stabilizes the FKBP12-FRB complex. In addition, fusion of MetRS
fragments to the termini of the ligand-binding domain of the estrogen receptor
yielded proteins whose Anl metabolic labeling was significantly enhanced when 4
hydroxytamoxifen (4-HT) was added to the growth medium. These findings suggest
that split MetRS can be fused to a range of ligand-binding proteins to create
aaRSs whose metabolic labeling activities depend upon post-translational
interactions with ligands.
PMID- 28419803
TI - Hydropersulfides: H-Atom Transfer Agents Par Excellence.
AB - Hydropersulfides (RSSH) are formed endogenously via the reaction of the gaseous
biotransmitter hydrogen sulfide (H2S) and disulfides (RSSR) and/or sulfenic acids
(RSOH). RSSH have been investigated for their ability to store H2S in vivo and as
a line of defense against oxidative stress, from which it is clear that RSSH are
much more reactive to two-electron oxidants than thiols. Herein we describe the
results of our investigations into the H-atom transfer chemistry of RSSH,
contrasting it with the well-known H-atom transfer chemistry of thiols. In fact,
RSSH are excellent H-atom donors to alkyl (k ~ 5 * 108 M-1 s-1), alkoxyl (k ~ 1 *
109 M-1 s-1), peroxyl (k ~ 2 * 106 M-1 s-1), and thiyl (k > 1 * 1010 M-1 s-1)
radicals, besting thiols by as little as 1 order and as much as 4 orders of
magnitude. The inherently high reactivity of RSSH to H-atom transfer is based
largely on thermodynamic factors; the weak RSS-H bond dissociation enthalpy (~70
kcal/mol) and the associated high stability of the perthiyl radical make the
foregoing reactions exothermic by 15-34 kcal/mol. Of particular relevance in the
context of oxidative stress is the reactivity of RSSH to peroxyl radicals, where
favorable thermodynamics are bolstered by a secondary orbital interaction in the
transition state of the formal H-atom transfer that drives the inherent
reactivity of RSSH to match that of alpha-tocopherol (alpha-TOH), nature's
premier radical-trapping antioxidant. Significantly, the reactivity of RSSH
eclipses that of alpha-TOH in H-bond-accepting media because of their low H-bond
acidity (alpha2H ~ 0.1). This affords RSSH a unique versatility compared to other
highly reactive radical-trapping antioxidants (e.g., phenols, diarylamines,
hydroxylamines, sulfenic acids), which tend to have high H-bond acidities.
Moreover, the perthiyl radicals that result are highly persistent under
autoxidation conditions and undergo very rapid dimerization (k = 5 * 109 M-1 s-1)
in lieu of reacting with O2 or autoxidizable substrates.
PMID- 28419804
TI - Simultaneous Reconstruction of the Medial and Lateral Collateral Ligaments for
Chronic Combined Ligament Injuries of the Ankle.
AB - BACKGROUND: Objective data on chronic injuries of the medial collateral ligament
(MCL) of the ankle are scarce. Chronic MCL injuries are frequently associated
with lateral collateral ligament (LCL) injuries. For patients with chronic
combined MCL and LCL injuries, the authors have performed simultaneous surgery of
the 2 ligaments. HYPOTHESIS: Simultaneous surgery of the 2 ligaments may be
effectively used to treat chronic combined MCL and LCL injuries. STUDY DESIGN:
Case series; Level of evidence, 4. METHODS: Surgical outcomes were evaluated in
29 consecutive patients presenting with chronic MCL and LCL injuries (30 ankles;
15 men and 14 women; mean age, 31 years; 13 competitive and 10 recreational
athletes). Preoperative and postoperative clinical outcomes were measured with
the Karlsson score and the Japanese Society for Surgery of the Foot (JSSF) ankle
hindfoot scale score. The patients underwent preoperative and postoperative
functional measurements and a radiological examination. In addition, preoperative
magnetic resonance imaging (MRI) results, arthroscopic findings, and histology of
the MCL were evaluated. RESULTS: Preoperatively, the deep fibers of the MCL did
not appear striated in 29 ankles, and high-intensity signal changes were observed
in 23 ankles on T2-weighted or gradient echo MRI. MCL ruptures were confirmed
with arthroscopic surgery. Medial impingement lesions and focal chondral lesions
were confirmed in 10 and 21 ankles, respectively. Histology of the reconstructed
MCL showed dense collagen fibers with vessels. The mean postoperative follow-up
period was 30 months (range, 24-52 months). There was a significant change
between preoperative and postoperative Karlsson scores (69.0 vs 96.1 points,
respectively; P < .0001) and JSSF scores (69.8 vs 94.5 points, respectively; P <
.0001). On varus and valgus stress radiography, the postoperative talar tilt
angle was significantly lower than the preoperative angle. Postoperative anterior
displacement on stress radiography was significantly lower than preoperative
anterior displacement. Postoperatively, all 23 athletes returned to their
preinjury level of sports participation. CONCLUSION: MCL insufficiency resulted
from medial ankle instability and medial impingement lesions. Outcomes in the
patients indicated that MCL reconstruction or resection of medial impingement
lesions, performed in addition to LCL reconstruction, is effective for treating
chronic combined MCL and LCL injuries of the ankle.
PMID- 28419805
TI - Hypoglossal Nerve Upper Airway Stimulator Implantation after Radiotherapy for
Head and Neck Malignancy.
PMID- 28419806
TI - Tracheal T-tubes for Long-term Management of the Unreconstructable Trachea in
Adults.
AB - Management of tracheostenosis in adult patients who are either medically
unreconstructable due to significant comorbidities or surgically
unreconstructable remains a challenge. The tracheal T-tube offers an excellent
permanent solution to the problem of the unreconstructable trachea. This article
reviews 3 patients who underwent tracheofissure and placement of a tracheal T
tube after failed prior attempts at repair of tracheal stenosis. The tracheal T
tubes have been maintained for 13, 15, and 36 years, and these patients have
enjoyed adequate phonatory and respiratory functions with the T-tube plugged and
functioning as an airway stent. There have been no major complications related to
use of the T-tube in this group of patients. The tracheal T-tube is a viable
alternative to long-term management of the unreconstructable trachea, allowing
patients airway support and adequate phonatory and respiratory function.
PMID- 28419807
TI - Otolaryngology Residency Program Research Resources and Scholarly Productivity.
AB - Objective To delineate research resources available to otolaryngology residents
and their impact on scholarly productivity. Study Design Survey of current
otolaryngology program directors. Setting Otolaryngology residency programs.
Subjects and Methods An anonymous web-based survey was sent to 98 allopathic
otolaryngology training program directors. Fisher exact tests and nonparametric
correlations were used to determine statistically significant differences among
various strata of programs. Results Thirty-nine percent (n = 38) of queried
programs responded. Fourteen (37%) programs had 11 to 15 full-time, academic
faculty associated with the residency program. Twenty (53%) programs have a
dedicated research coordinator. Basic science lab space and financial resources
for statistical work were present at 22 programs (58%). Funding is uniformly
provided for presentation of research at conferences; a minority of programs
(13%) only funded podium presentations. Twenty-four (63%) have resident research
requirements beyond the Accreditation Council for Graduate Medical Education
(ACGME) mandate of preparing a "manuscript suitable for publication" prior to
graduation. Twenty-five (67%) programs have residents with 2 to 3 active research
projects at any given time. None of the investigated resources were significantly
associated with increased scholarly output. There was no uniformity to research
curricula. Conclusions Otolaryngology residency programs value research,
evidenced by financial support provided and requirements beyond the ACGME
minimum. Additional resources were not statistically related to an increase in
resident research productivity, although they may contribute positively to the
overall research experience during training. Potential future areas to examine
include research curricula best practices, how to develop meaningful mentorship
and resource allocation that inspires continued research interest, and
intellectual stimulation.
PMID- 28419808
TI - Outcomes After 1-Stage Versus 2-Stage Revision Anterior Cruciate Ligament
Reconstruction.
AB - BACKGROUND: Revision anterior cruciate ligament reconstruction (ACLR) is becoming
increasingly common as the number of primary ACLR cases continues to rise.
Despite this, there are limited data on the outcomes of revision ACLR and even
less information specifically addressing the differences in 1-stage revision
reconstruction versus those performed in a 2-stage fashion after primary
reconstruction. PURPOSE: To compare the outcomes, patient satisfaction, and
failure rates of 1-stage versus 2-stage revision ACLR. STUDY DESIGN: Cohort
study; Level of evidence, 3. METHODS: All patients who underwent revision ACLR
between 2010 and 2014 by a single surgeon were collected, and skeletally mature
patients over the age of 17 years were included. Patients were excluded if they
were skeletally immature; had a previous intra-articular infection in the
ipsilateral knee; underwent a prior alignment correction procedure, cartilage
repair or transplant procedure, or meniscal allograft transplantation; or had an
intra-articular fracture. An ipsilateral or contralateral bone-patellar tendon
bone (BPTB) autograft was the graft of choice. A BPTB allograft was considered
for patients aged >=50 years, for any patient with an insufficient ipsilateral or
contralateral patellar tendon, or for those who chose not to have the
contralateral patellar tendon graft harvested. Patients completed a subjective
questionnaire preoperatively and at a minimum of 2 years postoperatively.
Magnetic resonance imaging and computed tomography of all knees were performed
preoperatively to assess for associated injuries and to evaluate the ACLR tunnel
size and location. Patients with malpositioned tunnels that would critically
overlap with an anatomically placed tunnel or those with tunnels >=14 mm in size
underwent bone grafting. RESULTS: A total of 88 patients met the inclusion
criteria for this study. There were 39 patients in the 1-stage revision surgery
group (19 male, 20 female) and 49 patients in the 2-stage revision surgery group
who underwent tunnel bone grafting first (27 male, 22 female). In both groups,
the 12-item Short Form Health Survey (SF-12) Physical Component Summary, Western
Ontario and McMaster Universities Arthritis Index, Lysholm, and Tegner activity
scale scores significantly improved from preoperatively to postoperatively. There
was no significant difference in the SF-12 Mental Component Summary score before
and after surgery in either group. Furthermore, there was no significant
difference in failure rates or other demographic data between the groups. We
observed 4 failures in the 1-stage reconstruction group (10.3%) and 3 failures in
the 2-stage reconstruction group (6.1%). CONCLUSION: In this study, objective
outcomes and subjective patient scores and satisfaction were not significantly
different between 1-stage and 2-stage revision ACLRs. Both groups had
significantly improved objective outcomes and patient subjective outcomes without
notable differences in failure rates. Further longitudinal studies comparing 1
stage and 2-stage revision ACLRs over a longer time frame are recommended.
PMID- 28419809
TI - Knee Biomechanics During Jogging After Arthroscopic Partial Meniscectomy: A
Longitudinal Study.
AB - BACKGROUND: Altered knee joint biomechanics is thought to play a role in the
pathogenesis of knee osteoarthritis and has been reported in patients after
arthroscopic partial meniscectomy (APM) while performing various activities.
Longitudinally, understanding knee joint biomechanics during jogging may assist
future studies to assess the implications of jogging on knee joint health in this
population. PURPOSE: To investigate knee joint biomechanics during jogging in
patients 3 months after APM and a healthy control group at baseline and 2 years
later at follow-up. STUDY DESIGN: Controlled laboratory study. METHODS: Seventy
eight patients who underwent medial APM and 38 healthy controls underwent a 3
dimensional motion analysis during barefoot overground jogging at baseline. Sixty
four patients who underwent APM and 23 controls returned at follow-up. External
peak moments (flexion and adduction) and the peak knee flexion angle during
stance were evaluated for the APM leg, non-APM leg (nonoperated leg), and control
leg. RESULTS: At baseline, the peak knee flexion angle was 1.4 degrees lower in
the APM leg compared with the non-APM leg ( P = .03). No differences were found
between the moments in the APM leg compared with the control leg (all P > .05).
However, the normalized peak knee adduction moment was 35% higher in the non-APM
leg compared with the control leg ( P = .008). In the non-APM leg, the normalized
peak knee adduction and flexion moments were higher compared with the APM leg by
16% and 10%, respectively, at baseline ( P <= .004). Despite the increase in the
peak knee flexion moment in the APM leg compared with the non-APM leg ( P <
.001), there were no differences in the peak knee flexion moment or any other
parameter assessed at 2-year follow-up between the legs ( P > .05). CONCLUSION:
Comparing the APM leg and control leg, no differences in knee joint biomechanics
during jogging for the variables assessed were observed. Higher knee moments in
the non-APM leg may have clinical implications for the noninvolved leg. Kinematic
differences were small (~1.4 degrees ) and therefore of questionable clinical
relevance. CLINICAL RELEVANCE: These results may facilitate future clinical
research regarding the implications of jogging on knee joint health in middle
aged, overweight patients after APM.
PMID- 28419810
TI - The Relationship of Static Tibial Tubercle-Trochlear Groove Measurement and
Dynamic Patellar Tracking.
AB - BACKGROUND: The tibial tubercle to trochlear groove (TT-TG) distance is used for
screening patients with a variety of patellofemoral joint disorders to determine
who may benefit from patellar medialization using a tibial tubercle osteotomy.
Clinically, the TT-TG distance is predominately based on static imaging with the
knee in full extension; however, the predictive ability of this measure for
dynamic patellar tracking patterns is unknown. PURPOSE: To determine whether the
static TT-TG distance can predict dynamic lateral displacement of the patella.
STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: The static
TT-TG distance was measured at full extension for 70 skeletally mature subjects
with (n = 32) and without (n = 38) patellofemoral pain. The dynamic patellar
tracking patterns were assessed from approximately 45 degrees to 0 degrees of
knee flexion by use of dynamic cine-phase contrast magnetic resonance imaging.
For each subject, the value of dynamic lateral tracking corresponding to the
exact knee angle measured in the static images for that subject was identified.
Linear regression analysis determined the predictive ability of static TT-TG
distance for dynamic patellar lateral displacement for each cohort. RESULTS: The
static TT-TG distance measured with the knee in full extension cannot accurately
predict dynamic lateral displacement of the patella. There was weak predictive
ability among subjects with patellofemoral pain ( r2 = 0.18, P = .02) and no
predictive capability among controls. Among subjects with patellofemoral pain and
static TT-TG distances 15 mm or more, 8 of 13 subjects (62%) demonstrated neutral
or medial patellar tracking patterns. CONCLUSION: The static TT-TG distance
cannot accurately predict dynamic lateral displacement of the patella. A large
percentage of patients with patellofemoral pain and pathologically large TT-TG
distances may have neutral to medial maltracking patterns.
PMID- 28419811
TI - Augmentation of Distal Biceps Repair With an Acellular Dermal Graft Restores
Native Biomechanical Properties in a Tendon-Deficient Model.
AB - BACKGROUND: The majority of distal biceps tendon injuries can be repaired in a
single procedure. In contrast, complete chronic tears with severe tendon
substance deficiency and retraction often require tendon graft augmentation. In
cases with extensive partial tears of the distal biceps, a human dermal allograft
may be used as an alternative to restore tendon thickness and biomechanical
integrity. HYPOTHESIS: Dermal graft augmentation will improve load to failure
compared with nonaugmented repair in a tendon-deficient model. STUDY DESIGN:
Controlled laboratory study. METHODS: Thirty-six matched specimens were organized
into 1 of 4 groups: native tendon, native tendon with dermal graft augmentation,
tendon with an attritional defect, and tendon with an attritional defect repaired
with a graft. To mimic a chronic attritional biceps lesion, a defect was created
by a complete tear, leaving 30% of the tendon's width intact. The repair
technique in all groups consisted of cortical button and interference screw
fixation. All specimens underwent cyclical loading for 3000 cycles and were then
tested to failure; gap formation and peak load at failure were documented.
RESULTS: The mean (+/-SD) load to failure (320.9 +/- 49.1 N vs 348.8 +/- 77.6 N,
respectively; P = .38) and gap formation (displacement) (1.8 +/- 1.4 mm vs 1.6 +/
1.1 mm, respectively; P = .38) did not differ between the native tendon groups
with and without graft augmentation. In the tendon-deficient model, the mean load
to failure was significantly improved with graft augmentation compared with no
graft augmentation (282.1 +/- 83.8 N vs 199.7 +/- 45.5 N, respectively; P = .04),
while the mean gap formation was significantly reduced (1.2 +/- 1.0 mm vs 2.7 +/-
1.4 mm, respectively; P = .04). The mean load to failure of the deficient tendon
with graft augmentation (282.1 N) compared with the native tendon (348.8 N) was
not significantly different ( P = .12). This indicates that the native tendon did
not perform differently from the grafted deficient tendon. CONCLUSION: In a
tendon-deficient, complete distal biceps rupture model, acellular dermal
allograft augmentation restored the native tendon's biomechanical properties at
time zero. The grafted tissue-deficient model demonstrated no significant
differences in the load to failure and gap formation compared with the native
tendon. As expected, dermal augmentation of attritional tendon repair increased
the load to failure and stiffness as well as decreased displacement compared with
the ungrafted tissue-deficient model. Tendons with their native width showed no
statistical difference or negative biomechanical consequences of dermal
augmentation. CLINICAL RELEVANCE: Dermal augmentation of the distal biceps is a
biomechanically feasible option for patients with an attritionally thinned-out
tendon.
PMID- 28419812
TI - Defining Quality in Head and Neck Reconstruction.
AB - Microvascular free flap reconstruction has now become the standard of care in the
reconstruction of selected head and neck defects. Although uncommon, flap failure
is a catastrophic event that results in significant patient morbidity, extended
length of hospitalization, and increased cost. However, there is currently no
gold standard for measuring the quality of a reconstructive center. Structure and
process outcomes have recently been developed, but outcome measures are still
lacking. Areas for future research include preoperative nutrition, preoperative
flap planning, intraoperative fluid management, appropriate thromboembolism
prophylaxis, consistent perioperative antibiotic regimens, skilled ancillary
staff, and clear outcome measures for performance measurement.
PMID- 28419813
TI - Do Clinical Practice Guidelines Improve Quality?
AB - Controversy exists surrounding how to best define and assess quality in the
health care setting. Clinical practice guidelines (CPGs) have been developed to
improve the quality of medical care by highlighting key clinical recommendations
based on recent evidence. However, data linking CPGs to improvements in outcomes
in otolaryngology are lacking. Numerous barriers contribute to difficulties in
translating CPGs to improvements in quality. Future initiatives are needed to
improve CPG adherence and define the impact of CPG recommendations on the quality
of otolaryngologic care provided to our patients.
PMID- 28419814
TI - High-Intensity Focused Ultrasound for Treatment of Symptomatic Benign Thyroid
Nodules: A Prospective Study.
AB - Purpose To evaluate first-year efficacy and changes in pressure symptoms and
health-related quality of life (HRQOL) after ultrasonographically (US) guided
high-intensity focused ultrasound (HIFU) ablation of symptomatic benign thyroid
nodules. Materials and Methods After ethics approval and informed consent were
obtained, a prospective trial was conducted. Patients with a symptomatic benign
thyroid nodule were given a choice of HIFU treatment or active surveillance.
Clinical and US examinations, pressure symptom scores (visual analog scale), and
HRQOL questionnaires (short form-12 survey) were evaluated at baseline and at 3,
6, and 12 months. The primary outcome was change in nodule volume after 12
months. The percentage of change in nodule volume was defined as the baseline
volume minus the volume at 12 months divided by the baseline volume times 100.
Ablation success was defined as a reduction in volume of greater than 50%. Nodule
volume was compared by using the paired t test. Continuous variables were
compared by using the Mann-Whitney U test, and categorical variables were
compared by using chi2 tests. Results Twenty-two patients underwent HIFU and 22
underwent active surveillance. Mean age was 53.11 years (range, 28-76 years) and
55.19 years (range, 41-70 years), respectively. The ratio of men to women was
2:20 and 1:21, respectively. The 12-month mean volume reduction +/- standard
deviation in the HIFU group was significant (68.87% +/- 15.27 [range, 47.35%
94.89%], P < .001) but not in the surveillance group (-2.11% +/- 6.29 [range,
15.64% to 12.70%], P > .05). Preablation nodule volume was the only determinant
of ablation success (odds ratio, 1.877; 95% confidence interval [CI]: 1.085,
3.249; P = .024). At 12 months, patients in the HIFU group had less swelling (P <
.001), lower pressure symptom scores (P < .001), and higher physical composite
scores (P = .006). Physical composite scores significantly correlated with 6
month reduction in nodule size (r = 0.768; 95% CI: 0.660, 0.930; P < .001) and 12
month reduction in nodule size (r = 0.704; 95% CI: 0.680, 940; P < .001).
Conclusion HIFU ablation of symptomatic benign thyroid nodules not only induced
significant shrinkage but also improved pressure symptom scores and HRQOL
throughout a 12-month period. (c) RSNA, 2017.
PMID- 28419815
TI - Diagnostic Performance of and Breast Tissue Changes at Early Breast MR Imaging
Surveillance in Women after Breast Conservation Therapy.
AB - Purpose To investigate the diagnostic performance and tissue changes in early (1
year or less) breast magnetic resonance (MR) imaging surveillance in women who
underwent breast conservation therapy for breast cancer. Materials and Methods
This prospective study was approved by the institutional review board, and
written informed consent was obtained. Between April 2014 and June 2016, 414
women (mean age, 51.5 years; range, 21-81 years) who underwent 422 early
surveillance breast MR imaging examinations (median, 6.0 months; range, 2-12
months) after breast conservation therapy were studied. The cancer detection
rate, positive predictive value of biopsy, sensitivity, specificity, accuracy,
and area under the curve of surveillance MR imaging, mammography, and
ultrasonography (US) were assessed. Follow-up was also obtained in 95 women by
using positron emission tomography (PET)/computed tomography (CT). Background
parenchymal enhancement (BPE) changes in the contralateral breast were assessed
according to adjuvant therapy by using the McNemar test. Results Of 11 detected
cancers, six were seen at MR imaging only, one was seen at MR imaging and
mammography, two were seen at MR imaging and US, one was seen at mammography
only, and one was seen at PET/CT only. Three MR imaging-depicted cancers were
observed at the original tumor bed, and two MR imaging-depicted cancers were
observed adjacent to the original tumor. Among two false-negative MR imaging
diagnoses (two cases of ductal carcinoma in situ), one cancer had manifested as
calcifications at mammography without differentiated enhancement at MR imaging,
and the other cancer was detected at PET/CT, but MR imaging results were negative
because of marked BPE, which resulted in focal lesion masking. The positive
predictive value of biopsy and the sensitivity, specificity, accuracy, and area
under the curve for MR imaging were 32.1% (nine of 28), 81.8% (nine of 11), 95.1%
(391 of 411), 94.7% (400 of 422), and 0.88, respectively. The sensitivity of
surveillance MR imaging (81.8%; 95% confidence interval [CI]: 48.2%, 97.7%) was
higher than that of mammography (18.2%; 95% CI: 2.3%, 51.8%) and US (18.2%; 95%
CI: 2.3%, 51.8%), with an overlap in CIs. The BPE showed a significant decrease
in the group of patients who received adjuvant chemotherapy (43 BPE decreases and
four BPE increases) and the group of patients who received hormone therapy (55
BPE decreases and two BPE increases) (P < .0001 for both). Conclusion Early MR
imaging surveillance after breast conservation therapy can be useful in patients
who have breast cancer, with superior sensitivity compared with that of
mammography and US. The BPE tends to be decreased at short-term follow-up MR
imaging in patients who receive adjuvant therapy. (c) RSNA, 2017.
PMID- 28419816
TI - High Rate of Osteoarthritis After Osteochondritis Dissecans Fragment Excision
Compared With Surgical Restoration at a Mean 16-Year Follow-up.
AB - BACKGROUND: Osteochondritis dissecans (OCD) is a disorder of subchondral bone
that causes adverse effects on the overlying cartilage and commonly affects the
knee. The incidence of OCD and its long-term effect on the knee joint are
controversial. Hypothesis/Purpose: The purpose of this study was to (1) evaluate
the rate of osteoarthritis and knee arthroplasty in a population-based cohort of
patients with OCD lesions treated operatively and (2) evaluate factors that may
predispose patients to knee osteoarthritis and arthroplasty. The investigators
hypothesized that OCD lesions diagnosed after skeletal maturity and treatment
with fragment excision would be predictive of a diagnosis of osteoarthritis.
STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The investigators
identified 221 patients (mean +/- SD age, 26.1 +/- 13.6 years) with OCD lesions
treated operatively between 1976 and 2010 and followed for 16.3 +/- 11.4 years
(mean +/- SD) from diagnosis. Information related to the diagnosis, laterality of
lesion, details of treatment, and progression to osteoarthritis was obtained from
the medical record. Surgical treatment was classified as fragment excision,
fragment preservation (lesion drilling and/or fragment fixation), or chondral
defect grafting (osteochondral allograft or autograft). Factors predictive of
osteoarthritis and arthroplasty were examined. RESULTS: There were 134 patients
in the fragment excision group, 78 patients in the fragment preservation group,
and 9 patients in the chondral defect grafting group. In the fragment excision
group, the cumulative incidence of osteoarthritis was 12.0% at 5 years, 17.0% at
10 years, 26.0% at 15 years, 39.0% at 20 years, and 70% at 30 years. The
cumulative incidence of arthroplasty was 2.0% at 5 years, 4.0% at 10 years, 4.0%
at 15 years, 10.0% at 20 years, and 32.0% at 30 years. In the fragment
preservation group, the cumulative incidence of osteoarthritis was 3.0% at 5
years, 7.0% at 10 years, 16.0% at 15 years, 25.0% at 20 years, and 51% at 30
years. The cumulative incidence of arthroplasty was 0.0% at 5 years, 0.0% at 10
years, 3.0% at 15 years, 6.0% at 20 years, and 11.0% at 30 years. No patients in
the chondral defect grafting group developed osteoarthritis or underwent
arthroplasty. Body mass index (BMI) greater than 25 kg/m2 (hazard ratio [HR] 3.3;
95% CI, 1.6-7.0), older age at diagnosis (HR 4.9; 95% CI, 1.8-17.3), and fragment
excision (HR 2.3; 95% CI, 1.2-4.6) were predictive of osteoarthritis. CONCLUSION:
OCD patients treated with fragment excision have a high rate of osteoarthritis
and knee arthroplasty at long-term follow-up. In contrast, patients treated with
fragment preservation or chondral defect grafting have lower rates of
osteoarthritis and arthroplasty. BMI greater than 25 kg/m2, older age at
diagnosis, and fragment excision were predictive of osteoarthritis.
PMID- 28419818
TI - Local Group 2 Innate Lymphoid Cells Promote Corneal Regeneration after Epithelial
Abrasion.
AB - Corneal injuries and infections are the leading cause of blindness worldwide.
Thus, understanding the mechanisms that control healing of the damaged cornea is
critical for the development of new therapies to promptly restore vision. Innate
lymphoid cells (ILCs) are a recently identified heterogeneous cell population
that has been reported to orchestrate immunity and promote tissue repair in the
lungs and skin after injury. However, whether ILCs can modulate the repair
process in the cornea remains poorly understood. We identified a population of
cornea-resident group 2 ILCs (ILC2s) in mice that express CD127, T1/ST2, CD90,
and cKit. This cell population was relatively rare in corneas at a steady state
but increased after corneal epithelial abrasion. Moreover, ILC2s were maintained
and expanded locally at a steady state and after wounding. Depletion of this cell
population caused a delay in corneal wound healing, whereas supplementation of
ILC2s through adoptive transfer partially restored the healing process. Further
investigation revealed that IL-25, IL-33, and thymic stromal lymphopoietin had
critical roles in corneal ILC2 responses and that CCR2- corneal macrophages were
an important producer of IL-33 in the cornea. Together, these results reveal the
critical role of cornea-resident ILC2s in the restoration of corneal epithelial
integrity after acute injury and suggest that ILC2 responses depend on local
induction of IL-25, IL-33, and thymic stromal lymphopoietin.
PMID- 28419817
TI - Objectively Measured Physical Activity in Patients After Anterior Cruciate
Ligament Reconstruction.
AB - BACKGROUND: Returning to a healthy level of physical activity is among the most
commonly discussed clinical goals for patients recovering from anterior cruciate
ligament reconstruction (ACLR). However, physical activity has not been
objectively measured in this population. PURPOSE: To investigate differences in
the mean time (min/d) spent in moderate-to-vigorous physical activity (MVPA) as
well as the daily step count (steps/d) between patients who underwent ACLR and
matched controls. A second purpose was to investigate relationships between MVPA
and objective assessments of the daily step count and Tegner and Marx activity
scales. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
Physical activity was assessed using ActiGraph accelerometers in 33 participants
with a history of primary unilateral or bilateral ACLR (mean time from surgery,
27.8 +/- 17.5 months; range, 6-67 months) as well as in 33 healthy controls
(matched on age, sex, and activity level). Participants wore the accelerometer
for 7 days and completed the International Knee Documentation Committee
subjective form and the Tegner and Marx activity scales. Independent t tests were
used to determine differences in each dependent variable per group. RESULTS:
Patients who underwent ACLR spent less time in MVPA (ACLR: 79.37 +/- 23.95 min/d;
control: 93.12 +/- 23.94 min/d; P = .02) and had a lower daily step count (ACLR:
8158 +/- 2780 steps/d; control: 9769 +/- 2785 steps/d; P = .02) compared with
healthy matched controls. However, the Marx (ACLR median: 11.0 [interquartile
range (IQR), 7-14]; control median: 12.0 [IQR, 8-13]; P = .85) and Tegner (ACLR
median: 6.0 [IQR, 5-8]; control median: 7.0 [IQR, 6-8]; P = .12) scores did not
differ between the groups, and no relationships were observed between objectively
measured physical activity and scale measures ( P > .05), except for a moderate
relationship between the Tegner score and daily step count in the ACLR group ( r
= 0.36, P = .04). Only 24% of patients who underwent ACLR met the guideline of
10,000 steps per day compared with 42% of controls. CONCLUSION: Patients who
underwent ACLR spent less time in MVPA and had a lower daily step count compared
with highly matched controls (age, sex, and activity level) with no history of
knee injuries. This was true despite being similar in activity levels, which
brings into question the utility of the Tegner and Marx activity scales.
PMID- 28419819
TI - Path to Illness Intrusiveness: What Symptoms Affect the Life of People Living
With Multiple Sclerosis?
AB - OBJECTIVE: To determine the direct and indirect effects of physical, emotional,
and cognitive impairments on illness intrusiveness in people with multiple
sclerosis (MS). DESIGN: Secondary analysis of a cross-sectional data set
collected in 2008 to identify sex differences in people living with MS. SETTING:
Three MS clinics. PARTICIPANTS: A random sample (N=189) of women and men
diagnosed with MS after 1995 were recruited and evaluated in 2008. INTERVENTIONS:
Not applicable. MAIN OUTCOME MEASURE: Illness Intrusiveness Rating Scale (updated
version using Rasch analysis). RESULTS: Path analysis yielded a model that was
significant (nonnormed fit index, .9913; normed fit index, .9846) with adequate
fit of the data to the model (goodness of fit index, .9781; chi2=21.41; P=.2084).
The model explained 55% of the variance of illness intrusiveness. Only emotional
and physical aspects were represented in the model because no cognitive
impairment stayed after variable reduction. The model showed the complete
mediation effect of fatigue on the physical function variables. CONCLUSIONS: This
project brings new evidence toward the conceptualization of illness intrusiveness
as a construct allowing future interventions that wish to target illness
intrusiveness or disease impact to be designed. It also presented statistical
evidence of the importance of treating fatigue not only as a symptom but also as
a consequence of other impairments.
PMID- 28419820
TI - Community acquired infections among refugees leading to Intensive Care Unit
admissions in Turkey.
AB - OBJECTIVES: Data on the impact of refugees on Intensive Care Units (ICUs) are
lacking in the literature, in particular for community-acquired (CA) infectious
diseases, for which they are known to be at higher risk. We did a descriptive,
multicenter study to analyze CA infections among refugee patients requiring ICU
admission. METHODS: Inclusion criteria were adult refugee patients admitted to an
ICU due to CA infections. Anonymized data were collected between January 1, 2010
and December 30, 2015 across 10 referral centers. RESULTS: 29.885 patients were
admitted to the ICUs in the study period. 37 patients were included the study,
the majority were from Syria (n=31, 83.8%). Mean (SD) age of the patients was
45.92+/-20.16years. The 5-year prevalence rate was 123.8 per 100.000 patients in
the ICUs. All patients had at least one comorbid condition. Forty-nine CA
infections were diagnosed. The most common CA infection was pneumonia (49%)
followed by urinary-tract infections (16.3%). 21 patients (56.7%) hospitalized in
the ICU had trauma history. Mortality rate was high at 22 patients (59.5%) with 5
(22.7%) deaths directly attributed to CA infections. CONCLUSIONS: Refugees
presented to ICUs with CA infections similar to the host populations (pneumonia
and urinary-tract infections) but had high mortality rates (59.5%). It seems that
Turkish ICUs were not congested with the refugee patients' influx for CA
infections. More research needs to be done to better understand how to deliver
preventative and timely health care services to this group of patients.
PMID- 28419821
TI - Expression of the enzymatically active legumain-like cysteine proteinase TvLEGU-1
of Trichomonas vaginalis in Pichia pastoris.
AB - The legumain-like cysteine proteinase TvLEGU-1 from Trichomonas vaginalis plays a
major role in trichomonal cytoadherence. However, its structure-function
characterization has been limited by the lack of a reliable recombinant
expression platform to produce this protein in its native folded conformation.
TvLEGU-1 has been expressed in Escherichia coli as inclusion bodies and all
efforts to refold it have failed. Here, we describe the expression of the
synthetic codon-optimized tvlegu-1 (tvlegu-1-opt) gene in Pichia pastoris strain
X-33 (Mut+) under the inducible AOX1 promoter. The active TvLEGU-1 recombinant
protein (rTvLEGU-1) was secreted into the medium when tvlegu-1-opt was fused to
the Aspergillus niger alpha-amylase signal peptide. The rTvLEGU-1 secretion was
influenced by the gene copy number and induction temperature. Data indicate that
increasing tvlegu-1-opt gene copy number was detrimental for heterologous
expression of the enzymatically active TvLEGU-1. Indeed, expression of TvLEGU-1
had a greater impact on cell viability for those clones with 26 or 29 gene copy
number, and cell lysis was observed when the induction was carried out at 30
degrees C. The enzyme activity in the medium was higher when the induction was
carried out at 16 degrees C and in P. pastoris clones with lower gene copy
number. The results presented here suggest that both copy number and induction
temperature affect the rTvLEGU-1 expression in its native-like and active
conformation.
PMID- 28419822
TI - Inhibitory effects of losartan and azelnidipine on augmentation of blood pressure
variability induced by angiotensin II in rats.
AB - Increased blood pressure variability has been shown to be associated with
cardiovascular morbidity and mortality. Recently we reported that continuous
infusion of angiotensin II not only elevated blood pressure level, but also
increased blood pressure variability in a manner assumed to be independent of
blood pressure elevation in rats. In the present study, the effects of the
angiotensin type I receptor blocker losartan and the calcium channel blocker
azelnidipine on angiotensin II-induced blood pressure variability were examined
and compared with that of the vasodilator hydralazine in rats. Nine-week-old male
Wistar rats were subcutaneously infused with 240 pmol/kg/min angiotensin II for
two weeks without or with oral administration of losartan, azelnidipine, or
hydralazine. Blood pressure variability was evaluated using a coefficient of
variation of blood pressure recorded every 15min under an unrestrained condition
via an abdominal aortic catheter by a radiotelemetry system. Treatment with
losartan suppressed both blood pressure elevation and augmentation of systolic
blood pressure variability in rats infused with angiotensin II at 7 and 14 days.
Azelnidipine also inhibited angiotensin II-induced blood pressure elevation and
augmentation of blood pressure variability; meanwhile, hydralazine attenuated the
pressor effect of angiotensin II, but had no effect on blood pressure
variability. In conclusion, angiotensin II augmented blood pressure variability
in an angiotensin type 1 receptor-dependent manner, and azelnidipine suppressed
angiotensin II-induced augmentation of blood pressure variability, an effect
mediated by the mechanism independent of the blood pressure-lowering action.
PMID- 28419823
TI - Genetic aspects of auto-immune profiles of healthy chickens.
AB - Auto-antibody profiles binding liver antigens differed between chicken lines
divergently selected for specific antibody responses to SRBC, and were affected
by ageing suggesting both genetic and environmental effects. Presence and levels
of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in
plasma at 5 weeks of age from 10 individual full sibs and their parents from 5
Hsrbc and 5 Lsrbc line families was studied to reveal genetic relations. Non
genetic maternal effects were studied by comparing auto-antibody profiles of 36
weeks old hens from 2 other unrelated lines with the profiles from their chicks
at hatch. IgM and IgG antibodies from parents and progeny from both Hsrbc and
Lsrbc lines bound CLL fragments. Significant line and generation differences and
their interactions were found for both isotypes. Higher staining of CLL fragments
was usually found for Hsrbc line birds. Lines were clustered by auto-antibody
profiles, but staining by birds of both lines in both generations was very
individual for IgG and IgM. The current data with full sibs therefore not
supported a genetic basis for auto-antibody profiles. IgG but not IgM auto
antibody profiles of chicks correlated with maternal auto-antibody profiles. The
results suggest that the auto-antibody repertoire of healthy chickens is largely
stochastically initiated and may be affected by environmental challenges during
ageing, but genetic mechanisms may underlie staining intensity of individual
bound CLL fragments. The present results suggest that identification of fragments
or profiles to be used at early age for genetic selection for health traits is
not feasible yet. Secondly, the IgM profile of neonatal chickens seems non
organised independent of the maternal profile, but the neonatal IgG profile is
much more related with the maternal profile. Consequences of these findings for
disease susceptibility or breeding for optimal health are discussed.
PMID- 28419824
TI - Effect of risperidone on serum homocysteine levels in first-episode, drug-naive
patients with schizophrenia.
AB - Some studies have shown that homocysteine (Hcy) levels are increased in patients
with schizophrenia, and may be involved in its pathophysiology. The purpose of
this study was to investigate the effect of the atypical antipsychotic drug
risperidone on serum Hcy levels and to explore the relationship between the
changes in Hcy levels and the therapeutic outcome, which, to our best knowledge
have not been investigated. Fifty-six first-episode and drug-naive inpatients
with schizophrenia were assigned to a 12-week treatment regime with risperidone.
Clinical efficacy was determined with the Positive And Negative Syndrome Scale
(PANSS). Serum Hcy levels were measured by sandwich enzyme-linked immunosorbent
assay in schizophrenia patients before and after the 12-week treatment, and the
values were compared with those of fifty-six age- and gender- matched healthy
controls. Serum Hcy levels were significantly higher in first-episode and drug
naive patients than in control subjects (11.18+/-4.53 vs. 5.99+/-3.61MUmol/L,
F=37.195, df=1, p=1.73*10-8). Moreover, a significant positive correlation
between Hcy levels and PANSS negative sub-score was observed (r=0.515; p=4.81*10
5). Serum Hcy levels were significantly decreased in patients after risperidone
treatment (baseline: 11.18+/-4.53MUmol/L vs. post-treatment: 8.98+/-4.07MUmol/L,
t=3.857, p=3.034*10-4). At post-treatment, there was a significant negative
relationship between serum Hcy levels and PANSS negative sub-scores (r=-0.288,
p=0.032). High Hcy levels at the onset of psychosis suggests that it may
contribute to the pathogenesis of schizophrenia and is related to clinical
psychopathology. Serum Hcy levels were significantly decreased in schizophrenia
patients after risperidone treatment.
PMID- 28419825
TI - Conversion of Pregabalin to 4-Isobutylpyrrolidone-2.
AB - Solid-state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica,
Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4
isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation
was implemented to further our understanding of the factors affecting the
conversion process.
PMID- 28419826
TI - Melting Process of the Peritectic Mixture of Lidocaine and Ibuprofen Interpreted
by Site Percolation Theory Model.
AB - Eutectic mixtures are often used in the design and delivery of drugs. In this
study, we examined the peritectic mixture of lidocaine (LDC) and ibuprofen (IBP)
using differential scanning calorimetry, Raman spectroscopy, and microscopy. The
obtained phase diagram showed that as the mixture was heated, first LDC melted at
293 K, then IBP dissolved in the liquefied LDC at 310 K, and finally all
remaining crystals melted. In the 1H NMR spectra, the signals of the carboxyl
group in IBP and amide or amine group in LDC shifted to the low magnetic field in
the IBP/LDC mixtures, because of the intermolecular interaction between these
moieties. Using FTIR spectroscopy, the kinetic "reaction" order of the melting
process in the mixtures with excess LDC, equimolar, and excess IBP was determined
to be +1/2, -1/2, and 0, respectively. The 2 contacts between the liquidus line
and the higher melting line at 310 K at IBP molar fractions of 1/3 and of 2/3
were explained on the basis of the site percolation theory.
PMID- 28419827
TI - Antihyperglycemic, antioxidant activities of tucuma oil (Astrocaryum vulgare) in
alloxan-induced diabetic mice, and identification of fatty acid profile by gas
chromatograph: New natural source to treat hyperglycemia.
AB - The aim of the study was to investigate the effect of the oral administration of
tucuma oil (Astrocaryum vulgare) on glucose and insulin levels, oxidative status,
and pancreatic genotoxic parameters of alloxan-induced diabetic mice. The animals
were divided into four groups (n = 6 each): control/water; control/tucuma oil;
diabetic/water; diabetic/tucuma oil treated for 14 days with 5.0 mL kg-1 via oral
gavage. Gas chromatograph characterization demonstrated that oleic/elaidic fatty
acid is the most abundant component present in this oil, followed by palmitic and
stearic fatty acids. Our results demonstrated an increase (p < 0.05) in water and
food intake, blood glucose, thiobarbituric acid reactive species (TBARS) levels,
damage index, and frequency of damage; conversely body weight, insulin levels,
catalase (CAT) and superoxide dismutase (SOD) activities, and cell viability were
decreased in the diabetic/water group compared to the control/water group. The
treatment with tucuma oil prevented these alterations in the diabetic/tucuma oil
group compared to the diabetic/water group, and restored these parameters near to
the control/water group. In summary, our findings demonstrated that treatment
with tucuma oil causes a hypoglycemic effect improving insulin levels and
antioxidant/oxidant status, and has a protector effect against pancreatic damage
induced by oxidative stress in alloxan-induced diabetic mice.
PMID- 28419828
TI - Hypoglycemic and hypolipidemic effects of a polysaccharide from flower buds of
Lonicera japonica in streptozotocin-induced diabetic rats.
AB - Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM).
In this study, one fraction of the crude polysaccharides extracted from Lonicera
japonica flower buds (LJP) were investigated for its hypolipidaemic and
hypoglycaemic activities by means of streptozotocin (STZ)-induced diabetic rats.
Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP
for 42 days, the food and water intake and the levels of sugar and insulin in
blood for the diabetic rats were drastically decreased, while the contents of
liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate
kinase and hexokinase were obviously increased (p<0.01 or p<0.05). The levels of
total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterin
(LDL-C) and very-low-density lipoprotein-cholesterin (VLDL-C) were significantly
descended, while high-density lipoprotein-cholesterin (HDL-C) was significantly
ascended (p<0.01 or p<0.05). In addition, the oxidant stress in liver was
restored as well. The results suggested that LJP could be considered as an
ingredient of functional foods for diabetes, and this is the first report about
the hypoglycemic and hypolipidemic effects of the polysaccharides extracted from
Lonicera japonica.
PMID- 28419829
TI - Characterization of polyhydroxyalkanoates produced by Synechocystis salina from
digestate supernatant.
AB - The current commercial production of polyhydroxyalkanoates (PHA) is based on
heterotrophic bacteria, using organic carbon sources from crops. To avoid the
competition with food and feed production, cyanobacteria, metabolising PHA from
carbon dioxide can be used. This research focuses on the investigation of the
thermal and rheological properties of PHA polymers accumulated by Synechocystis
salina, which had been cultivated in digestate supernatant and a mineral medium.
The dried bacterial cells had a polymer content of 5.5-6.6%. The relevance of the
derived PHA polymers for the common melt polymer processing was correlated with
their molecular mass distribution as well as with their thermal and rheological
properties. The determined thermal and rheological properties showed that PHA
polymers accumulated by S. salina on digestate supernatant or mineral medium are
comparable with the commercial available poly(3-hydroxybutyrate). However, the
results showed that PHA polymers in general require modification before melt
processing to increase their stability in the molten state.
PMID- 28419830
TI - Creative cognition and dopaminergic modulation of fronto-striatal networks:
Integrative review and research agenda.
AB - Creative cognition is key to human functioning yet the underlying neurobiological
mechanisms are sparsely addressed and poorly understood. Here we address the
possibility that creative cognition is a function of dopaminergic modulation in
fronto-striatal brain circuitries. It is proposed that (i) creative cognition
benefits from both flexible and persistent processing, (ii) striatal dopamine and
the integrity of the nigrostriatal dopaminergic pathway is associated with
flexible processing, while (iii) prefrontal dopamine and the integrity of the
mesocortical dopaminergic pathway is associated with persistent processing. We
examine this possibility in light of studies linking creative ideation, divergent
thinking, and creative problem-solving to polymorphisms in dopamine receptor
genes, indirect markers and manipulations of the dopaminergic system, and
clinical populations with dysregulated dopaminergic activity. Combined, studies
suggest a functional differentiation between striatal and prefrontal dopamine:
moderate (but not low or high) levels of striatal dopamine benefit creative
cognition by facilitating flexible processes, and moderate (but not low or high)
levels of prefrontal dopamine enable persistence-driven creativity.
PMID- 28419831
TI - Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the
rat bed nucleus of the stria terminalis.
AB - The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in
the forebrain, composed of multiple sub-nuclei, each with discrete populations of
neurons. Progress in understanding BNST function, both in the adult and during
postnatal maturation, is dependent upon a more complete characterization of
neuronal phenotypes in the BNST. The aim of the current study was to define the
molecular phenotype of one postnatal BNST neuronal population, in order to
identify molecular factors that may underlie both (protein marker-related)
immaturity, and secondly, the transience of this phenotype. This BNST population
was originally identified by high, but transient expression of the EGR1
transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI).
The current results confirm a high level of Egr1 activation in postnatal day 10
(PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of
transient activation in female brains. Apparent cellular immaturity in this
population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3,
was found to be uncorrelated with both key neuronal regulator protein expression
(SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a
partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa
decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co
expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at
PN40. The transcriptional basis of the transient and partial catecholaminergic
phenotype was investigated by analysing TFs known to maintain adult dopaminergic
(TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack
forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons
had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear
receptor that is critical for adult maintenance of midbrain dopamine neurons.
These results detail the molecular features of an immature neuronal phenotype,
and reveal TF deficiencies that may underlie postnatal transience of the
phenotype.
PMID- 28419832
TI - Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2
pathway to alleviate ethanol-induced hepatic injury.
AB - Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly
effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic
properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have
infrequently been reported thus far. In the present study, C57BL/6 mice were fed
with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as
a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY
significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and
triglyceride deposition induced by chronic alcohol exposure. In addition, DMY
dramatically attenuated the alcohol-triggered elevation of the level of
inflammatory cytokines and partially recovered hepatic pathological changes.
Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1
in the liver and simultaneously ameliorated disordered nuclear localization of NF
kappaB and Nrf2 to exert its hepatoprotective effects. Further mechanistic
exploration suggested that DMY activated Nrf2, possibly mediated through the
autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2
demonstrated that the p62 upregulation caused by DMY contributes to a positive
feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and
autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and
the inflammatory response in the pathological progression of ALD.
PMID- 28419833
TI - Sexual selection, sexual isolation and pheromones in Drosophila melanogaster
strains after long-term maintaining on different diets.
AB - Evolution of reproductive isolation may be a consequence of a variety of signals
used in courtship and mate preferences. Pheromones play an important role in both
sexual selection and sexual isolation. The abundance of pheromones in Drosophila
melanogaster may depend on different environmental factors, including diet. The
aim of this study was to ascertain to which degree principal pheromones affect
sexual selection in D. melanogaster. We used D. melanogaster strains reared for
14 years on four substrates: standard cornmeal substrate and those containing
tomato, banana and carrot. We have previously determined that long-term
maintaining of these dietary strains resulted in differences in their cuticular
hydrocarbons profile (CHs). In this work, we have tested the level of sexual
selection and sexual isolation between aforementioned strains. We found that the
high levels of cis-vaccenyl acetate, 7-pentacosene and 7,11-nonacosadiene in the
strain reared on a substrate containing carrot affected the individual
attractiveness and influenced sexual isolation between flies of this strain and
flies reared on a substrate containing banana. Based on these results, long-term
different diets, may contribute, to sexual behaviour of D. melanogaster via the
effects of principal pheromones.
PMID- 28419834
TI - Sex differences in autonomic response and situational appraisal of a competitive
situation in young adults.
AB - Competition is a social stressor capable of eliciting physiological responses
modulated by the outcome. The main objective of this study was to analyze the
psychophysiological changes associated with competition and its outcome in men
and women, taking into account the role of situational appraisal. To this end,
112 young people (46 men and 66 women) participated in a laboratory task in a
competitive or non-competitive condition, while Blood Pressure (BP), Heart Rate
Variability (HRV), and Skin Conductance (SC) responses were measured. Our results
indicate that competition elicits higher systolic blood pressure (SBP) than a non
competitive task; in addition, winners presented a greater R-R decrease from
baseline to task, greater R-R Recovery, and lower frustration and external
attribution than losers. Regarding sex, men perceived their opponent's capacity
to be lower and their own capacity to be greater than women did, and they also
showed higher R-R decreases and lower SC increases. In conclusion, we found a
complex pattern of different psychophysiological responses to competition
associated with outcome and sex in a laboratory competition. This result could be
related to the use of more passive or active coping strategies.
PMID- 28419835
TI - The architecture and function of the chromatin replication machinery.
AB - Genomic DNA in eukaryotic cells is packaged into nucleosome arrays. During
replication, nucleosomes need to be dismantled ahead of the advancing replication
fork and reassembled on duplicated DNA. The architecture and function of the core
replisome machinery is now beginning to be elucidated, with recent insights
shaping our view on DNA replication processes. Simultaneously, breakthroughs in
our mechanistic understanding of epigenetic inheritance allow us to build new
models of how histone chaperones integrate with the replisome to reshuffle
nucleosomes. The emerging picture indicates that the core eukaryotic DNA
replication machinery has evolved elements that handle nucleosomes to facilitate
chromatin duplication.
PMID- 28419836
TI - Enzymatic behavior of laccase following interaction with gamma-CD and
immobilization into PCL nanofibers.
AB - This study examines the effects of CD use on enzymatic activity, following enzyme
immobilization into nanofibers. There is almost no research available on the
change in enzyme activity following interaction with cyclodextrin and electrospun
nanofiber mats together. Laccase enzyme was immobilized into nanofibrous
structures by various techniques, with and without gamma-CD addition, and the
enzymatic activity of the laccase was analyzed. SEM, XRD, and FTIR analyses were
used for the characterization of the resulting structures. Our results showed
that cyclodextrin use has a positive effect on the enzyme's activity, and
increases its stability. The enzymes treated by cyclodextrin showed activation
after complex formation trials, and no activation loss or enzyme denaturation was
detected. Our conclusions were supported by the enzyme activity test results,
which also showed that immobilization by encapsulation methods gave better
activity results than layering methods. Another important finding concerned the
laccase's stable characteristics that helped to maintain its enzyme activation
after the freeze drying process. Among all test groups, the best activity result
was recorded by laccase-gamma-CD complex encapsulated PCL nanofibers with 96.48
U/mg.
PMID- 28419837
TI - Identification and molecular cloning of novel transcripts of the human kallikrein
related peptidase 10 (KLK10) gene using next-generation sequencing.
AB - Tissue kallikrein and kallikrein-related peptidases (KLKs) form the largest group
of serine proteases in the human genome, sharing many structural and functional
characteristics. Multiple alternative transcripts have been reported for the most
human KLK genes, while many of them are aberrantly expressed in various
malignancies, thus possessing significant prognostic and/or diagnostic value.
Alternative splicing of cancer-related genes is a common cellular mechanism
accounting for cancer cell transcriptome complexity, as it affects cell cycle
control, proliferation, apoptosis, invasion, and metastasis. In this study, we
describe the identification and molecular cloning of eight novel transcripts of
the human KLK10 gene using 3' rapid amplification of cDNA ends (3' RACE) and next
generation sequencing (NGS), as well as their expression analysis in a wide panel
of cell lines, originating from several distinct cancerous and normal tissues.
Bioinformatic analysis revealed that the novel KLK10 transcripts contain new
alternative splicing events between already annotated exons as well as novel
exons. In addition, investigation of their expression profile in a wide panel of
cell lines was performed with nested RT-PCR using variant-specific pairs of
primers. Since many KLK mRNA transcripts possess clinical value, these newly
discovered alternatively spliced KLK10 transcripts appear as new potential
biomarkers for diagnostic and/or prognostic purposes or as targets for
therapeutic strategies.
PMID- 28419838
TI - Peptidoglycan accelerates granulopoiesis through a TLR2- and MyD88-dependent
pathway.
AB - Granulopoiesis is accelerated during Gram-negative bacterial infection through
activation of toll-like receptor 4 (TLR4). In this study, we tested whether
activation of TLR2 promotes granulopoiesis by using the well-known TLR2 agonist,
peptidoglycan (PGN). Neutrophils in bone marrow and spleen, and plasma
granulocyte colony-stimulating factor (G-CSF) were increased in mice that had
received intraperitoneal PGN administration. Incorporation of BrdU into bone
marrow neutrophils increased, demonstrating that PGN accelerated granulopoiesis.
Treatment of bone marrow cells (BMCs) with PGN increased neutrophils in vitro and
promoted the secretion of G-CSF from Ly-6G-Ly-6C+ monocytes. The accelerated
granulopoiesis caused by PGN was not seen in TLR2-deficient and MyD88-deficient
BMCs. Additionally, PGN induced G-CSF production in human umbilical vein
endothelial cells. These findings demonstrate that PGN promotes the secretion of
G-CSF from monocytes and endothelial cells, leading to the acceleration of
granulopoiesis. Our results illustrate that bacterial recognition by TLR2
facilitates granulopoiesis during Gram-positive bacterial infection.
PMID- 28419839
TI - Near-infrared laser irradiation improves the development of mouse pre
implantation embryos.
AB - The aim of the present study was to assess the effects of near-infrared laser
irradiation on the in vitro development of mouse embryos. Female ICR mice were
superovulated with pregnant mare serum gonadotropin and human chorionic
gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were
collected 40 h after administering hCG and cultured in M16 medium. Two-cell
embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula
(approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were
irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse
monitoring system and the timing of blastocyst hatching was evaluated. Some of
the irradiated blastocysts were transferred to the uterine horns of
pseudopregnant recipients immediately after irradiation. Pregnancy rates, and
offspring growth and fertility, were evaluated. Near-infrared laser irradiation
increased the speed of in vitro mouse embryo development. In irradiated
blastocysts, hatching was faster than in control (non-irradiated) blastocysts
(18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to
18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups
were born alive. When 182 control blastocysts were transferred to 17
pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking
pups were born alive. The growth trajectories (up to 5 weeks) of offspring from
irradiated blastocysts were similar to those from control blastocysts. Second
generation offspring from transplanted animals were all fertile. These results
indicate that near-infrared laser irradiation improves the quality of mouse
embryo development in vitro, and increases the live birth rate without affecting
the normality of the offspring. Thus, the near-infrared laser method may enhance
the quality of embryos and contribute to improvements in reproductive
technologies in mammals.
PMID- 28419840
TI - Potent osteogenic activity of a novel imidazobenzimidazole derivative, IBIP.
AB - Bone mass is controlled by a balance between bone resorption and formation by
osteoclasts and osteoblasts, respectively. An imbalance between osteoblasts and
osteoclasts increases the risk of osteoporosis and fractures. Although inhibition
of osteoclasts is beneficial for preventing and treating osteoporosis, enhanced
bone formation through activation of osteoblast differentiation can be a more
promising therapeutic approach. In this study, we attempted to isolate small
molecules that promote osteoblast differentiation and found that IBIP (3-(2,3
dimethoxyphenyl)-1-[9-methyl-2-phenyl-9H-imidazo[1,2-a]benzimidazol-3-yl]-2
propen-1-one) was a potent activator of osteoblast differentiation. Upon bone
morphogenetic protein-2 (BMP2) stimulation, IBIP promoted osteoblast
differentiation and increased the expression of osteoblast-specific gene markers,
such as osterix and alkaline phosphatase, in a dose-dependent manner. The
phosphorylation of SMADs and extracellular signal-regulated kinase (ERK)
increased after IBIP treatment. While enhanced SMAD phosphorylation by IBIP was
abolished by a BMP inhibitor, IBIP-induced ERK phosphorylation was sustained in
the presence of this inhibitor, but was decreased by an ERK kinase inhibitor.
Suppression of IBIP-induced SMAD and ERK phosphorylation diminished osteoblast
differentiation. Most importantly, IBIP enhanced bone formation and calcification
in a BMP2-independent manner in vitro and advanced the skeletal development of
zebrafish larvae in vivo. Collectively, IBIP may have beneficial effects on bone
loss through potentiation of bone formation.
PMID- 28419842
TI - Erratum.
PMID- 28419841
TI - Buffered 1% Lidocaine With Epinephrine Can Be as Effective as Nonbuffered 2%
Lidocaine With Epinephrine for Maxillary Field Block.
AB - PURPOSE: Buffering local anesthetics with epinephrine (Epi) offers clinicians
options not often considered. This study assessed outcomes for pulpal anesthesia,
pain on injection, and time to midface numbness for buffered 1% lidocaine with
1:100,000 Epi versus nonbuffered 2% lidocaine with 1:100,000 Epi. MATERIALS AND
METHODS: In this trial with a randomized, crossover design, buffered 1% lidocaine
was compared with nonbuffered 2% lidocaine. Subjects were adult volunteers who
served as their own controls. The predictor variables were alternate drug
formulations. The outcome variables were subjects' responses to cold and electric
pulp testing (EPT) stimulation of the maxillary first molar and canine, pain
levels during the injection, and time to midface numbness. After maxillary field
blocks with 40 mg of buffered lidocaine or 80 mg of nonbuffered lidocaine,
subjects reported pain on injection and responses of the maxillary first molar
and canine after cold and EPT stimulation. Teeth were tested before field block
and at 30-minute intervals until a positive response was detected. Two weeks
later, subjects were tested with the alternate drug combinations. For all outcome
variables, assessment of treatment difference, calculated as 1% buffered minus 2%
nonbuffered, was performed with the Wilcoxon rank sum test with significance at P
< .05. RESULTS: More of the 24 subjects were women and Caucasian. The median age
was 23.5 years (interquartile range, 21, 25 years), and the median body weight
was 155 lb (interquartile range, 128.5, 176.5 lb). Pain levels during the
injection were significantly lower for 1% buffered lidocaine, with P = .04. Times
to response after injection were not significantly different between the 2 drug
formulations for the cold test on a molar, with P = .08, or the cold test on a
canine, with P = .22. However, times to response were significantly longer for
nonbuffered drugs for EPT on the molar and canine, both with P = .01.
CONCLUSIONS: Buffering 1% lidocaine with 1:100,000 Epi reduces the pain on
injection with a maxillary field block and results in similar lengths of pulpal
anesthesia tested with a cold stimulus as compared with nonbuffered 2% lidocaine
with 1:100,000 Epi.
PMID- 28419843
TI - A Review of In-Office Dynamic Image Navigation for Extraction of Complex
Mandibular Third Molars.
AB - PURPOSE: We performed a retrospective review of in-office removal of complex
mandibular third molars with a dynamic image navigation system (DINS). MATERIALS
AND METHODS: A retrospective review was conducted of cases completed from 2010 to
2014 by a single oral and maxillofacial surgeon. The average age of the patients
was 47 years (range, 27 to 72 years). Extraction complexity was classified with
Juodzbalys and Daugela's classification system. The included study cases had
complexity scores of 9 or greater. Each patient received custom intraoral splints
to secure the tracking array and underwent cone beam computed tomography image
acquisition. All surgical procedures were performed with a precalibrated tracking
straight handpiece under dynamic navigation. RESULTS: All 25 cases were treated
successfully with the use of the DINS. Twelve of these cases were associated with
pathologic lesions. Three patients were noted to have inferior alveolar nerve
paresthesia. One patient sustained a pathologic fracture at week 2. Postoperative
infections were noted in 7 cases, 2 of which had a pre-existing infection. One
patient reported temporary limitation of mouth opening. A coronectomy was
performed in 1 case. CONCLUSIONS: We present results using a new technology, the
DINS, for removal of complex mandibular third molars. Potential advantages are 1)
improved visualization and localization of anatomic structures such as the
inferior alveolar nerve, lingual cortical plate, and adjacent roots; 2) improved
control during osteotomy; 3) decreased surgical access requirements and reduction
in overall bone removal; 4) ability to perform complex procedures successfully in
an in-office setting; 5) decreased surgical time resulting from improved
visualization; and 6) potential use as a teaching tool. Possible limitations of
the use of an in-office DINS include increased cost, increased time attributed to
presurgical planning, initial learning curve, and optical array interference by
the surgeon or assistants during surgery.
PMID- 28419844
TI - Triple-Cut Computer-Aided Design-Computer-Aided Modeling: More Oncologic Safety
Added to Precise Mandible Modeling.
AB - PURPOSE: Computer-aided design-computer-aided modeling (CAD-CAM) has become
standard in mandibular reconstruction because it offers better outcomes.
Occasionally, the reconstructive plans need to be changed intraoperatively and
the custom-made prefabricated devices may become inadequate. We present an
efficient adjunct to the standard CAD-CAM technique that resolves this problem.
MATERIALS AND METHODS: Customized surgical devices with our "triple-cut" concept
were used in 5 patients for mandibular reconstruction with free fibula flap (4
after mandibular resection for squamous cell carcinoma and 1 after mandibular
osteoradionecrosis). In all patients the mandibular and fibular cutting guides
were provided with 3 different cutting levels per side. RESULTS: Three different
cutting levels on the mandible permitted an accurate resection based on the
intraoperative needs. The corresponding 3 "cutting levels" on the fibula created
perfectly matching segments of vascularized bone. Good contact of bony segments
was obtained in all patients. CONCLUSIONS: The prefabricated triple-cut cutting
guides make changing the dimensions of bony resection, while still using the
prefabricated CAD-CAM reconstructive plate, possible.
PMID- 28419845
TI - Does Orthognathic Surgery Cause or Cure Temporomandibular Disorders? A Systematic
Review and Meta-Analysis.
AB - PURPOSE: There is still controversy about whether orthognathic surgery negatively
or positively affects temporomandibular disorders (TMDs). The purpose of this
study was to determine whether orthognathic surgery has a beneficial or
deleterious effect on pre-existing TMDs. MATERIALS AND METHODS: A systematic
review and meta-analysis were conducted based on Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched 3 major
databases to locate all pertinent articles published from 1980 to March 2016. All
subjects in the various studies were stratified a priori into 9 categories based
on subdiagnoses of TMDs. The predictor variables were those patients with pre
existing TMDs who underwent orthognathic surgery in various subgroups. The
outcome variables were maximal mouth opening and signs and symptoms of a TMD
before and after orthognathic surgery based on the type of osteotomy. The meta
analysis was performed using Comprehensive Meta-Analysis software (Biostat,
Englewood, NJ). RESULTS: A total of 5,029 patients enrolled in 29 studies were
included in this meta-analysis. There was a significant reduction in TMDs in
patients with a retrognathic mandible after bilateral sagittal split osteotomy
(BSSO) (P = .014), but no significant difference after bimaxillary surgery (BSSO
and Le Fort I osteotomy) (P = .336). There was a significant difference in
patients with prognathism after isolated BSSO or intraoral vertical ramus
osteotomy and after combined BSSO and Le Fort I osteotomy (P = .001), but no
significant difference after BSSO (P = .424) or bimaxillary surgery (intraoral
vertical ramus osteotomy and Le Fort I osteotomy) (P = .728). CONCLUSIONS:
Orthognathic surgery caused a decrease in TMD symptoms for many patients who had
symptoms before surgery, but it created symptoms in a smaller group of patients
who were asymptomatic before surgery. The presence of presurgical TMD symptoms or
the type of jaw deformity did not identify which patients' TMDs would improve,
remain the same, or worsen after surgery.
PMID- 28419846
TI - Bit1 Regulates Cell Migration and Survival in Oral Squamous Cell Carcinoma.
AB - PURPOSE: Increasing evidence has shown that Bcl-2 inhibitor of transcription 1
(Bit1) involves a variety of biological processes in the process of tumor
development and progression. We hypothesized that Bit1 would be overexpressed in
oral squamous cell carcinoma (OSCC); therefore, we examined Bit1 gene expression
and protein production, as well as explored the effect of elevated Bit1 levels on
OSCC cells. MATERIALS AND METHODS: We investigated the use of quantitative real
time reverse transcription-polymerase chain reaction and immunohistochemistry
analysis for Bit1 messenger RNA and protein levels. We used 75 OSCC specimens, 25
tumor-adjacent dysplasia specimens, and 25 normal oral tissue samples that
matched OSCC specimens in this study. We also transfected Bit1 complementary DNA
into human oral cancer cells (Tca8113) to further investigate the potential role
of Bit1 in OSCC. RESULTS: We found that Bit1 levels in OSCC tissues were
significantly higher than those in tumor-adjacent dysplasia specimens and normal
oral tissue (P < .05). We also confirmed that Bit1 overexpression in the cytosol
of Tca8113 cells induced apoptosis. CONCLUSIONS: Our findings suggest Bit1
overexpression may contribute to oral cancer cell survival and dissemination. In
the future, Bit1 may be an important diagnostic and therapeutic target.
PMID- 28419847
TI - The Oral and Maxillofacial Surgery Anesthesia Team Model.
AB - Oral and maxillofacial surgeons have been providing safe anesthesia to their
patients using the anesthesia team model; this has allowed access to care for
patients that have significant anxiety. The AAOMS strives to maintain the
excellent safety record of the anesthesia team model by creating simulation
programs in anesthesia, regularly updating the office anesthesia evaluation
program, convening anesthesia safety conferences and strengthening the standards
in our training programs. Through these efforts, our delivery of anesthesia to
our patients will remain safe and effective.
PMID- 28419848
TI - Toll-like receptor activation, vascular endothelial function, and hypertensive
disorders of pregnancy.
AB - Aberrant innate immune system activation in the mother contributes greatly to the
development of hypertension during pregnancy. Numerous groups have elicited
vascular inflammation, endothelial dysfunction, and hypertension in animals
during gestation by directly activating Toll-like receptors. Additionally,
several experimental therapies that reduce pro-inflammatory immune cells and
cytokines restore vascular endothelial function and normalize blood pressure.
This review will summarize the research demonstrating that an excessive maternal
innate immune response is sufficient to cause vascular inflammation and
endothelial dysfunction, which contributes to the development of hypertension
during pregnancy. Dampening the vascular inflammation caused by immune responses
may reduce the incidence and severity of hypertensive disorders of pregnancy.
PMID- 28419849
TI - RIFM fragrance ingredient safety assessment, isoamyl formate, CAS Registry Number
110-45-2.
PMID- 28419851
TI - An emergent functional parcellation of the temporal cortex.
AB - The temporal lobe has been associated with various cognitive functions which
include memory, auditory cognition and semantics. However, at a higher level of
conceptualisation, all of the functions associated with the temporal lobe can be
considered as lying along one major axis; from modality-specific to modality
general processing. This paper used a spectral reordering technique on resting
state and task-based functional data to extract the major organisational axis of
the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations
were performed on resting-state scans from 71 participants and active semantic
task scans from 23 participants acquired using dual echo gradient echo planar
imaging in order to preserve signal in inferior temporal cortex. The resulting
organisational axis was consistent (over dataset and hemisphere) and progressed
from superior temporal gyrus and posterior inferior temporal cortex to
ventrolateral anterior temporal cortex. A hard parcellation separated a posterior
(superior temporal and posterior fusiform and inferior temporal gyri) and an
anterior cluster (ventrolateral anterior temporal lobe). The functional
connectivity of the hard clusters supported the hypothesis that the connectivity
gradient separated modality-specific and modality-general regions. This
hypothesis was then directly tested by performing a VOI analysis upon an
independent semantic task-based data set including auditory and visually
presented stimuli. This confirmed that the ventrolateral anterior aspects of the
temporal lobe are associated with modality-general processes whilst posterior and
superior aspects are specific to certain modalities, with the posterior inferior
subregions involved in visual processes and superior regions involved in
audition.
PMID- 28419850
TI - Overpressure blast injury-induced oxidative stress and neuroinflammation response
in rat frontal cortex and cerebellum.
AB - BACKGROUND & AIM: Overpressure blast-wave induced brain injury (OBI) and its long
term neurological outcome pose significant concerns for military personnel. Our
aim is to investigate the mechanism of injury due to OBI. METHODS: Rats were
divided into 3 groups: (1) Control, (2) OBI (exposed 30psi peak pressure, 2
2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and
brain (cortex and cerebellum) tissues were collected at 24h post injury. RESULTS:
The neurological examination score was worse in OBI and r-OBI (4.2+/-0.6 and
3.7+/-0.5, respectively) versus controls (0.7+/-0.2). A significant positive
correlation between lung and brain edema was found. Malondialdehyde (index for
lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex
(p<0.05) and cerebellum (p<0.01-0.001). The glutathione (endogenous antioxidant)
level decreased in cortex (p<0.01) and cerebellum (p<0.05) of r-OBI group when
compared with the controls. Myeloperoxidase activity indicating neutrophil
infiltration, was significantly (p<0.01-0.05) elevated in r-OBI. Additionally,
tissue thromboplastin activity, a coagulation marker, was elevated, indicating a
tendency to bleed. NGF and NF-kappaB proteins along with Iba-1 and GFAP
immunoreactivity significantly augmented in the frontal cortex demonstrating
microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin,
were also elevated. CONCLUSION: OBI triggers both inflammation and oxidative
injury in the brain. This data in conjunction with our previous observations
suggests that OBI triggers a cascade of events beginning with impaired cerebral
vascular function leading to ischemia and chronic neurological consequences.
PMID- 28419852
TI - Reliability of volumetric and surface-based normalisation and smoothing
techniques for PET analysis of the cortex: A test-retest analysis using [11C]SCH
23390.
AB - Parametric voxelwise analysis is a commonly used tool in neuroimaging, as it
allows for identification of regions of effects in the absence of a strong a
priori regional hypothesis by comparing each voxel of the brain independently.
Due to the inherent imprecision of single voxel measurements, spatial smoothing
is performed to increase the signal-to-noise ratio of single-voxel estimates. In
addition, smoothing compensates for imprecisions in anatomical registration, and
allows for the use of cluster-based statistical thresholding. Smoothing has
traditionally been applied in three dimensions, without taking the tissue types
of surrounding voxels into account. This procedure may be suitable for
subcortical structures, but is problematic for cortical regions for which grey
matter often constitutes only a small proportion of the smoothed signal. New
methods have been developed for cortical analysis in which voxels are sampled to
a surface, and smoothing is restricted to neighbouring regions along the cortical
grey matter in two dimensions. This procedure has recently been shown to decrease
intersubject variability and bias of PET data. The aim of this study was to
compare the variability, bias and test-retest reliability of volumetric and
surface-based methods as they are applied in practice. Fifteen healthy young
males were each measured twice using the dopamine D1 receptor radioligand
[11C]SCH-23390, and analyses were performed at the level of individual voxels and
vertices within the cortex. We found that surface-based methods yielded higher
BPND values, lower coefficient of variation, less bias, better reliability and
more precise estimates of parametric binding. All in all, these results suggest
that surface-based methods exhibit superior performance to volumetric approaches
for voxelwise analysis of PET data, and we advocate for their use when a ROI
based analysis is not appropriate.
PMID- 28419853
TI - Listeria monocytogenes meningitis in the Netherlands, 1985-2014: A nationwide
surveillance study.
AB - OBJECTIVES: Listeria monocytogenes can cause sepsis and meningitis. We report
national surveillance data on L. monocytogenes meningitis in the Netherlands,
describing incidence changes, genetic epidemiology and fatality rate. METHODS: We
analyzed data from the Netherlands Reference Laboratory of Bacterial Meningitis
for cases of L. monocytogenes meningitis. Strains were assessed by serotyping and
bacterial population structure by multi-locus sequence typing. RESULTS: A total
of 375 cases of Listeria meningitis were identified between 1985 and 2014. Peak
incidence rates were observed in neonates (0.61 per 100,000 live births) and
older adults (peak at 87 year; 0.53 cases per 100,000 population of the same
age). Neonatal listerial meningitis decreased 17-fold from 1.95 per 100,000 live
births between 1985 and 1989, to 0.11 per 100,000 live births between 2010 and
2014. Overall case fatality rate was 31%, in a multivariate analysis older age
and concomitant bacteremia were associated with mortality (both p < 0.01). Clonal
complexes (CC) CC1, CC2 and CC3 decreased over time from respectively 32% to 12%,
33% to 9% and 10% to 2% (all p < 0.001), while CC6 increased from 2% to 26% (p <
0.001). CONCLUSIONS: The incidence of neonatal listerial meningitis has declined
over the past 25 years. The genotype CC6 has become the predominant genotype in
listerial meningitis in the Netherlands. Mortality of listeria meningitis has
remained high.
PMID- 28419854
TI - A formalin-inactivated vaccine provides good protection against Vibrio harveyi
infection in orange-spotted grouper (Epinephelus coioides).
AB - Vibrio harveyi is one of the most common threats to farmed grouper, so
considerable efforts are in practice to control the pathogen. This study presents
a highly effective vaccine against V. harveyi in the orange-spotted grouper with
the help of a single intraperitoneal immunization. The vaccine candidate was in
form of whole, formalin-inactivated V. harveyi cells combined with a
metabolizable ISA763 AVG adjuvant. Our results indicated that the vaccine
triggered a remarkably higher expression level of interleukin (IL)-1beta, IL-6,
IL-8, and IL-10 in the groupers' kidneys and spleens, as recorded after 1 and 3
days of immunization. Antibody titers were significantly elevated in the
vaccinated fish. A pivotal observation was that the vaccine highly protected the
grouper from a homologous V. harveyi strain challenge with relative percentage
survival values of 100% and 91.7% at 6 and 12 weeks post-immunization,
respectively. Vaccinated fish also demonstrated strong cross-protection against a
heterologous bacterial isolate challenge. Therefore, the inactivated V. harveyi
vaccine is a promising candidate that could stimulate good immune responses and
confer remarkable protection in farmed groupers.
PMID- 28419856
TI - Adenoma Prevalence in Blacks and Whites Having Equal Adherence To Screening
Colonoscopy: The National Colonoscopy Study.
PMID- 28419855
TI - A Randomized Trial of Silymarin for the Treatment of Nonalcoholic
Steatohepatitis.
AB - BACKGROUND & AIMS: Silymarin is a complex mixture of 6 major flavonolignans and
other minor polyphenolic compounds derived from the milk thistle plant Silybum
marianum; it has shown antioxidant, anti-inflammatory and antifibrotic effects,
and may be useful in patients with nonalcoholic fatty liver disease (NAFLD). We
aimed to study the efficacy of silymarin in patients with nonalcoholic
steatohepatitis (NASH)-the more severe form of NAFLD. METHODS: We performed a
randomized, double-blind, placebo-controlled trial of consecutive adults with
biopsy-proven NASH and a NAFLD activity score (NAS) of 4 or more at a tertiary
care hospital in Kuala Lumpur, Malaysia, from November 2012 through August 2014.
Patients were randomly assigned to groups given silymarin (700 mg; n = 49
patients) or placebo (n = 50 patients) 3 times daily for 48 weeks. After this 48
week period, liver biopsies were repeated. The primary efficacy outcome was a
decrease of 30% or more in NAS; findings from 48-week liver biopsies were
compared with those from the baseline biopsy. Secondary outcomes included changes
in steatosis, lobular inflammation, hepatocyte ballooning, NAS and fibrosis
score, and anthropometric measurements, as well as glycemic, lipid, and liver
profiles and liver stiffness measurements. RESULTS: The percentage of patients
achieving the primary efficacy outcome did not differ significantly between the
groups (32.7% in the silymarin group vs 26.0% in the placebo group; P = .467). A
significantly higher proportion of patients in the silymarin group had reductions
in fibrosis based on histology (reductions of 1 point or more; 22.4%) than did
the placebo group (6.0%; P = .023), and based on liver stiffness measurements
(decrease of 30% or more; 24.2%) than did the placebo group (2.3%; P = .002). The
silymarin group also had significant reductions in mean aspartate
aminotransferase to platelet ratio index (reduction of 0.14, P = .011 compared
with baseline), fibrosis-4 score (reduction of 0.20, P = .041 compared with
baseline), and NAFLD fibrosis score (reduction of 0.30, P < .001 compared with
baseline); these changes were not observed in the placebo group (reduction of
0.07, P = .154; increase of 0.18, P = .389; and reduction of 0.05, P = .845,
respectively). There was no significant difference between groups in number of
adverse events; adverse events that occurred were not attributed to silymarin.
CONCLUSIONS: In a randomized trial of 99 patients, we found that silymarin (700
mg, given 3 times daily for 48 weeks) did not reduce NAS scores by 30% or more in
a significantly larger proportion of patients with NASH than placebo. Silymarin
may reduce liver fibrosis but this remains to be confirmed in a larger trial. It
appears to be safe and well tolerated. ClinicalTrials.gov: NCT02006498.
PMID- 28419857
TI - Making a Great Journal Even Better.
PMID- 28419858
TI - Reply.
PMID- 28419859
TI - Endoscopic Ultrasound Liver Biopsies Accurately Predict the Presence of Fibrosis
in Patients With Fatty liver.
PMID- 28419860
TI - Pedunculated Laryngeal Hemangioma in a Patient With Suspected Atypical Symptoms
of GERD.
PMID- 28419861
TI - Agroecological and environmental factors influence Barley yellow dwarf viruses in
grasslands in the US Pacific Northwest.
AB - Plant pathogens can play a role in the competitive interactions between plant
species and have been understudied in native prairies, which are declining
globally, and in Conservation Reserve Program (CRP) lands in the United States.
Barley/Cereal yellow dwarf virus (B/CYDV) are among the most economically
important disease-causing agents of small grain cereal crops, such as wheat, and
are known to infect over 150 Poaceae species, including many of the grass species
present in prairies and CRP lands. Field surveys of Poaceae species were
conducted in endangered Palouse Prairie and CRP habitats of southeastern
Washington and adjacent northern Idaho, USA from 2010 to 2012 to examine for the
presence of B/CYDV among plant hosts and aphid vectors. Viral species were
identified via cloning and sequencing. Landscape, soil and climate data were
retrieved from USDA-NASS and USDA-NRCS databases. Analyses were conducted to
examine effects of diverse agroecological and environmental factors on virus
prevalence. A total of 2271 grass samples representing 30 species were collected;
28 of these were infected with BYDV in at least one location. BYDV infection was
detected at every CRP and prairie remnant sampled, with an overall infection of
46%. BYDV-SGV and BYDV-PAV were the only two B/CYDV species encountered, with
BYDV-SGV being more prevalent. Sampling time (season) and host plant identity
were the main variables explaining variation in virus prevalence among sites.
BYDV was more prevalent in perennial compared to annual grass species. Aphids
were encountered only once suggesting non-colonizing aphids, potentially from
neighboring cereal fields, are responsible for disease spread in these habitats.
BYDV prevalence increased in sampled habitats as cereal crop cover increased
within a 1-km radius of a habitat patch. Results demonstrate moderate to high and
persistent prevalence of BYDV in an endangered grassland habitat. Species
composition and susceptibility to pathogens should be considered when creating
seed mixes for CRP sites, especially in relation to agricultural crops and
diseases in a region. Future work exploring host abundance, competence and
habitat utilization by vectors is required to fully elucidate BYDV ecology and
epidemiology in grassland habitats.
PMID- 28419862
TI - The effect of tDCS over the right temporo-parietal junction on pain empathy.
AB - Empathy is a complex psychological phenomenon crucial for social perception and
interactions. Several lines of evidence suggest that the right temporo-parietal
junction is involved in self-other control mechanisms that play an important role
in empathic responses. However, limited direct evidence of the involvement of
this region in empathic responses is currently available. In this study,
inhibitory transcranial direct current stimulation over this region influenced
empathic responses to others' pain. It was found that compared to participants
that received anodal or sham transcranial direct current stimulation,
participants who received cathodal transcranial direct current stimulation over
the right temporo-parietal junction perceived the pain of others as less intense
compared to sham stimulation and showed decreased late event related potentials
to facial expressions of pain. Furthermore, it was found the stimulation had no
significant effect on measures of sensorimotor resonance and physiological
responses to pain in others. Our results demonstrate that the right temporo
parietal junction plays a role in empathic responses and that its inhibition can
decrease behavioural and cerebral measures related to the cognitive-evaluative
component of empathy. It is proposed that the right temporo-parietal junction is
a valid stimulation target to study the influence of self-other control in
empathic processes and could be useful to study the involvement of this region
observed in clinical conditions characterized by altered empathic responses.
PMID- 28419863
TI - Cellular stress response in human Muller cells (MIO-M1) after bevacizumab
treatment.
AB - Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely
used in the treatment of retinal vascular diseases. However, due to the essential
role Muller cell derived-VEGF plays in the maintenance of retinal neurons and
glial cells, cell viability is likely to be affected by VEGF inhibition. We
therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Muller
cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media
containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium
only. Cell viability was determined with the trypan blue exclusion test and MTT
assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin
content were quantified by immunohistochemistry. Gene expression was evaluated by
real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell
viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced
apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25
and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3
mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with
bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with
structural protein abnormalities, with decreased GFAP and vimentin content and
upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not
significantly affect MIO-M1 cell viability, it led to metabolic and molecular
changes (apoptosis, autophagy and structural abnormalities) suggestive of
significant cellular toxicity.
PMID- 28419864
TI - How to be a good neighbour: Facilitation and competition between two co-flowering
species.
AB - Empirical evidence suggests that co-flowering species can facilitate each other
through shared pollinators. However, the extent to which one co-flowering species
can relieve pollination limitation of another while simultaneously competing for
abiotic resource has rarely been examined. Using a deterministic model we
explored the demographic outcome for one ("focal") species of its co-occurrence
with a species that shares pollinators and competes for both pollinator
visitation and abiotic resources. In this paper we showed how the overall impact
can be positive or negative, depending on the balance between enhanced
fertilization versus increased competition. Our model could predict the density
of co-flowering species that will maximize the pollination rate of the focal
species by attracting pollinators. Because that density will also give rise to
competitive effects, a lower density of co-flowering species is required for
optimizing the trade-off between enhanced fertilization and competition so as to
give the maximum possible facilitation of reproduction in the focal species.
Results were qualitatively different when we considered attractiveness of the co
flowering species, as opposed to its density, because attractiveness, unlike
density, had no effect on competition for abiotic resources. Whereas unattractive
neighbours would not bring in pollinators, very attractive neighbours would
captivate pollinators, not sharing them with the focal species. Thus optimal
benefit to the focal species came at intermediate levels of attractiveness in the
co-flowering species. This intermediate level of attractiveness in co-flowering
species simultaneously maximized pollination and overall facilitation of
reproduction for the focal species. The likelihood of facilitation was predicted
to decline with the selfing rate of the focal species, revealing an indirect cost
for an inbreeding mating system. Whether a co-flowering species can be
facilitative depends on the way pollinators respond to the plant density: only a
Type III functional response for visitation rate can result in facilitation. Our
model provided both a conceptual framework and precise quantitative measures for
determining the impacts of a neighbouring co-flowering species on reproduction.
PMID- 28419865
TI - The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic
arthritis in mice.
AB - Septic arthritis is a severe and rapidly debilitating disease associated with
severe joint pain, inflammation and oxidative stress. Nitroxyl (HNO) has become a
nitrogen oxide of significant interest due to its pharmacological endpoints that
are potentially favorable for treating varied diseases. However, whether HNO also
serves as a treatment to septic arthritis is currently unknown. The aim of this
study was to investigate the effect of the HNO donor, Angeli's salt (AS), in the
outcome of chronic Staphylococcus aureus (S. aureus)-induced septic arthritis in
mice. Daily treatment with AS inhibited mechanical hyperalgesia and inflammation
(edema, leukocyte migration, cytokines release and NF-kappaB activation, and
oxidative stress) resulting in reduced disease severity (clinical course,
histopathological changes, proteoglycan levels in the joints, and
osteoclastogenesis). In addition, AS decreased the number of S. aureus colony
forming unities in synovial tissue, enhanced the bactericidal effect of
macrophages and inhibited the worsening of systemic inflammatory response
(leukocyte counts in the lung and systemic proinflammatory cytokine
concentration). Our results suggest for the first time the therapeutic potential
of AS in a model of septic arthritis by mechanisms involving microbicidal
effects, anti-inflammatory actions and reduction of disease severity.
PMID- 28419866
TI - O-Aminobenzoyl-S-nitrosoglutathione: A fluorogenic, cell permeable, pseudo
substrate for S-nitrosoglutathione reductase.
AB - S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can
catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD+
dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the
spontaneous reaction between formaldehyde and glutathione). While initially
recognized as the enzyme that is involved in formaldehyde detoxification,
increasing amount of evidence has shown that GSNOR also plays a significant role
in nitric oxide mediated signaling through its modulation of protein S
nitrosothiol signaling. In humans, GSNOR/S-nitrosothiols have been implicated in
the etiology of several diseases including lung cancer, cystic fibrosis, asthma,
pulmonary hypertension, and neuronal dysfunction. Currently, it is not possible
to monitor the activity of GSNOR in live cells. In this article, we present a new
compound, O-aminobenzoyl-S-nitrosoglutathione (OAbz-GSNO), which acts as a
fluorogenic pseudo-substrate for GSNOR with an estimated Km value of 320uM. The
weak OAbz-GSNO fluorescence increases by approximately 14 fold upon reduction of
its S-NO moiety. In live cell imaging studies, OAbz-GSNO is readily taken up by
primary pulmonary endothelial cells and localizes to the same perinuclear region
as GSNOR. The perinuclear OAbz-GSNO fluorescence increases in a time dependent
manner and this increase in fluorescence is abolished by siRNA knockdown of GSNOR
or by treatment with GSNOR-specific inhibitors N6022 and C3. Taken together,
these data demonstrate that OAbz-GSNO can be used as a tool to monitor the
activity of GSNOR in live cells.
PMID- 28419867
TI - Sustained blockade of ascorbic acid transport associated with marked SVCT1 loss
in rat hepatocytes containing increased ascorbic acid levels after partial
hepatectomy.
AB - The liver has an extraordinary regenerative capacity in response to partial
hepatectomy (PHx), which develops with neither tissue inflammation response nor
alterations in the whole organism. This process is highly coordinated and it has
been associated with changes in glutathione (GSH) metabolism. However, there are
no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and
GSH act integrally as an antioxidant system that protects cells and tissues from
oxidative damage and imbalance observed in a variety of diseases that affect the
liver. Although rat hepatocytes are able to synthesize AA and GSH, which are the
providers of AA for the whole organism, they also acquire AA from extracellular
sources through the sodium-coupled ascorbic acid transporter-1 (SVCT1). Here, we
show that hepatocytes from rat livers subjected to PHx increase their GSH and AA
levels from 1 to 7 days post hepatectomy, whose peaks precede the peak in cell
proliferation observed at 3 days post-hepatectomy. The increase in both
antioxidants was associated with higher expression of the enzymes involved in
their synthesis, such as the modifier subunit of enzyme glutamine cysteine ligase
(GCLM), glutathione synthetase (GS), gulonolactonase (GLN) and gulonolactone
oxidase (GULO). Importantly, rat hepatocytes, that normally exhibit kinetic
evidence indicating only SVCT1-mediated transport of AA, lost more than 90% of
their capacity to transport it at day 1 after PHx without evidence of recovery at
day 7. This observation was in agreement with loss of SVCT1 protein expression,
which was undetectable in hepatocytes as early as 2h after PHx, with partial
recovery at day 7, when the regenerated liver weight returns to normal. We
conclude that after PHx, rat hepatocytes enhance their antioxidant capacity by
increasing GSH and AA levels prior to the proliferative peak. GSH and AA are
increased by de novo synthesis, however paradoxically hepatocytes from rat
subjected to PHx also suppress their capacity to acquire AA from extracellular
sources through SVCT1.
PMID- 28419868
TI - Ciprofloxacin resistance in uropathogenic Escherichia coli isolates causing
community-acquired urinary infections in Brasilia, Brazil.
AB - OBJECTIVES: Considering the global concern of ciprofloxacin resistance, the aim
of this study was to evaluate the characteristics of ciprofloxacin-resistant (CIP
R) Escherichia coli isolated from patients with community-acquired urinary tract
infections (UTIs) in Brasilia, Brazil. METHODS: CIP-R E. coli isolated from
different outpatients between July 2013 and April 2014 in a tertiary hospital
were analysed for antibiotic resistance profile, phylotype, uropathogenic E. coli
(UPEC) virulence genes, clonal relationship by enterobacterial repetitive
intergenic consensus PCR (ERIC-PCR), and multilocus sequence typing (MLST).
RESULTS: Among the 324 UPEC analysed, 263 (81.2%) were ciprofloxacin-sensitive
and 61 (18.8%) were CIP-R. Antibiogram analysis of the 61 CIP-R strains showed
that 45 (73.8%) were also multidrug-resistant. The most prevalent phylogroups
were A and B2 (26/61 and 18/61, respectively). traT (53/61) and aer-traT (24/61)
were the most common gene and genotype observed. Dendrogram analysis found that
multidrug resistance and virulence genes were distributed among CIP-R strains
independently of clonality and phylogroup. Six ERIC clusters (strains sharing
>=85% genetic similarity) were observed. MLST analysis of all strains of each
cluster identified sequence types (STs) associated with worldwide antimicrobial
resistance dissemination, including B2-ST131 and ST410, as well as STs not yet
associated with antimicrobial resistance propagation, such as ST1725 and ST179.
CONCLUSIONS: These results demonstrate that ciprofloxacin resistance
dissemination by UPEC causing community-acquired UTIs was associated with
multidrug resistance and was promoted by pandemic and non-pandemic STs, a
concerning scenario for the local population.
PMID- 28419869
TI - Allodemic distribution of plasmids co-harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB
in Klebsiella pneumoniae is the main source of extended-spectrum beta-lactamases
in Uruguay's paediatric hospital.
AB - OBJECTIVES: This study aimed to describe the characteristics of clinical isolates
of extended-spectrum beta-lactamase (ESBL)-producing enterobacteria (EPE) in
Uruguay's paediatric hospital. METHODS: ESBLs, qnr alleles and aac(6')-Ib-cr were
sought and characterised in EPE isolated between March 2010 and March 2012.
Transfer of resistance determinants was assessed by conjugation. Incompatibility
(Inc) groups, plasmid toxin-antitoxin systems (TAS) and plasmid size were
determined in transconjugants. Clonality was analysed by pulsed-field gel
electrophoresis. Multilocus sequence typing was done for ESBL-producing
Klebsiella pneumoniae. RESULTS: A total of 77 EPE isolates were characterised,
comprising 43% K. pneumoniae, 19.5% Serratia marcescens, 19.5% Escherichia coli,
17% Enterobacter cloacae and 1% Klebsiella oxytoca. ESBLs belonged mainly to the
blaCTX-M family (69.6%) [blaCTX-M-15 (45%) and blaCTX-M-2 (31%)]. The aac(6')-Ib
cr/qnrB duplex was the most frequently detected plasmid-mediated quinolone
resistance mechanism; this association was detected in K. pneumoniae harbouring
blaCTX-M-15. Transconjugants were obtained for 71% of the EPE. Amongst
transconjugants, certain combinations were found between ESBLs and Inc group,
e.g. IncA/C-blaCTX-M-2, IncHI1/HI2-blaCTX-M-9 and IncHI1/HI2-blaSHV-12. In
addition, the combination ccdAB-blaCTX-M-15 was also found. K. pneumoniae
isolates harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB showed allodemic behaviour,
with a predominance of ST14, ST45 and ST48. CONCLUSIONS: In this study,
epidemiological changes in ESBL distribution could be explained by the spread of
K. pneumoniae harbouring blaCTX-M-15/aac(6')-Ib-cr/qnrB, encoded mainly on
conjugative plasmids featuring ccdAB TAS. Since reports of TAS in K. pneumoniae
plasmids are scarce, new strategies are needed to combat intrinsic selection
pressure exerted by the association, in conjugative plasmids, of resistance
mechanisms with TAS.
PMID- 28419870
TI - Methicillin-resistant Staphylococcus aureus nasal colonisation amongst healthcare
workers in Kurdistan Region, Iraq.
AB - OBJECTIVES: The aim of this study was to determine the prevalence of nasal
carriage of methicillin-resistant Staphylococcus aureus (MRSA) among healthcare
workers (HCWs) compared with non-HCWs at Duhok city, Kurdistan Region, northern
Iraq. METHODS: A total of 182 HCWs with different occupations and working in
different hospital units as well as 198 non-HCWs were recruited. Nasal swab
samples were collected and were inoculated on mannitol salt agar and incubated at
35 degrees C for 48h. Isolates identified as S. aureus underwent antimicrobial
sensitivity testing to oxacillin. MRSA isolates were selected and investigated
for presence of the mecA gene. RESULTS: Among the HCWs, 41/182 (22.5%) were
carriers of S. aureus compared with 37/198 (18.7%) non-HCWs (P=0.4). Amongst the
S. aureus carriers, 25/41 strains (61.0%) isolated from HCWs were MRSA compared
with 8/37 strains (21.6%) isolated from non-HCWs (P=0.039). The mean age of MRSA
carriers was 35.6+/-6.7years compared with 30+/-5.8years for MRSA non-carriers
(P=0.0177). The mean working years of MRSA carriers was significantly higher than
that of MRSA non-carriers (7.8+/-5.5years vs. 3.9+/-5.3years; P=0.04).
CONCLUSIONS: The prevalence of MRSA was very high amongst HCWs. Regular screening
of carriers is required for prevention of nosocomial infections.
PMID- 28419871
TI - Short-term inhibition of GABAergic IPSCs induced by association of pre- and
postsynaptic activation in the neonatal hippocampus.
AB - Activity-dependent plasticity including short and long-term depression
accompanied by a reduction in transmitter release probability has been
demonstrated in both inhibitory and excitatory synapses. In the neonatal
hippocampus, repetitive postsynaptic depolarization is followed by presynaptic
alterations of the efficacy of GABAAergic transmission. Both facilitation and
inhibition have been observed, but the mechanisms underlying this plasticity have
not yet been elucidated. In the present experiment, repetitive postsynaptic
depolarization by itself did not cause marked alterations of spontaneous
inhibitory postsynaptic currents (sIPSCs). Activation of presynaptic neurons by
increasing extracellular K+ concentration ([K+]o) temporarily induced
facilitation of sIPSCs, but successive repetitive depolarizations transiently
reduced the current frequency. This newly discovered inhibition was expressed
presynaptically, could not be induced by postsynaptic depolarization alone, and
was facilitated by the activation of NMDA receptors. IPSC inhibition was
suppressed using the antagonists of metabotropic glutamate receptors (mGluRs) or
muscarinic ACh receptors (mAChRs). Furthermore, transient inhibition was reduced
by an antagonist of the type 1 cannabinoid receptor (CB1 receptor). The effect of
CB1 receptor agonist on the sIPSCs was potentiated by [K+]o elevation, implying a
role for the [K+]o elevation other than the release of transmitters. These
results show that weak postsynaptic activation, when combined with presynaptic
activation, leads to an inhibition of GABAergic synapses in the neonatal
hippocampus. This inhibition is mediated by a mechanism involving mGluRs, mAChRs,
and CB1 receptors, and potentiated by NMDA receptor activation.
PMID- 28419872
TI - Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction
in female mice from two models of Rett syndrome.
AB - Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by
severe behavioral and physiological symptoms. Mutations in the methyl CpG binding
protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there
is no cure for this devastating disorder. Recently we have demonstrated that
neurobehavioral and brain molecular alterations can be rescued in a RTT mouse
model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R).
This member of the serotonin receptor family, crucially involved in the
regulation of brain structural plasticity and cognitive processes, can be
stimulated by systemic repeated treatment with LP-211, a brain-penetrant
selective agonist. The present study extends previous findings by demonstrating
that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial
respiratory chain impairment, oxidative phosphorylation deficiency and the
reduced energy status in the brain of heterozygous female mice from two highly
validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211
treatment completely restored the radical species overproduction by brain
mitochondria in the MeCP2-308 model and partially recovered the oxidative
imbalance in the more severely affected MeCP2-Bird model. These results provide
the first evidence that RTT brain mitochondrial dysfunction can be rescued
targeting the brain 5-HT7R and add compelling preclinical evidence of the
potential therapeutic value of LP-211 as a pharmacological approach for this
devastating neurodevelopmental disorder.
PMID- 28419873
TI - Arrestin-2 and arrestin-3 differentially modulate locomotor responses and
sensitization to amphetamine.
AB - Arrestins play a prominent role in shutting down signaling via G protein-coupled
receptors. In recent years, a signaling role for arrestins independent of their
function in receptor desensitization has been discovered. Two ubiquitously
expressed arrestin isoforms, arrestin-2 and arrestin-3, perform similarly in the
desensitization process and share many signaling functions, enabling them to
substitute for one another. However, signaling roles specific to each isoform
have also been described. Mice lacking arrestin-3 (ARR3KO) were reported to show
blunted acute responsiveness to the locomotor stimulatory effect of amphetamine
(AMPH). It has been suggested that mice with deletion of arrestin-2 display a
similar phenotype. Here we demonstrate that the AMPH-induced locomotion of male
ARR3KO mice is reduced over the 7-day treatment period and during AMPH challenge
after a 7-day withdrawal. The data are consistent with impaired locomotor
sensitization to AMPH and suggest a role for arrestin-3-mediated signaling in the
sensitization process. In contrast, male ARR2KO mice showed enhanced early
responsiveness to AMPH and the lack of further sensitization, suggesting a role
for impaired receptor desensitization. The comparison of mice possessing one
allele of arrestin-3 and no arrestin-2 with ARR2KO littermates revealed reduced
activity of the former line, consistent with a contribution of arrestin-3
mediated signaling to AMPH responses. Surprisingly, ARR3KO mice with one arrestin
2 allele showed significantly reduced locomotor responses to AMPH combined with
lower novelty-induced locomotion, as compared to the ARR3KO line. These data
suggest that one allele of arrestin-2 is unable to support normal locomotor
behavior due to signaling and/or developmental defects.
PMID- 28419875
TI - Falls in people with Parkinson's disease: A prospective comparison of community
and home-based falls.
AB - BACKGROUND: Falls are common and debilitating in people with Parkinson's disease
(PD) and restrict participation in daily activities. Understanding circumstances
of falls in the community and at home may assist clinicians to target therapy
more effectively. OBJECTIVE: To compare the characteristics of community and home
fallers and the circumstances that contribute to falls in people living with PD.
METHODS: People with mild-moderately severe PD (n=196) used a daily falls diary
and telephone hotline to report prospectively the occurrence, location and
circumstances of falls over 14 months. RESULTS: 62% of people with PD fell, with
most falling at least once in the community. Compared to people who fell at home,
the community-only fallers had shorter durations of PD (p=0.012), less severe
disease (p=0.008) and reported fewer falls in the year prior to the study
(p=0.003). Most falls occurred while people were ambulant, during postural
transitions and when medication was working well. Community-based falls were
frequently attributed to environmental factors such as challenging terrains
(p<0.001), high attention demands (p=0.029), busy or cluttered areas (p<0.001)
and tasks requiring speed (p=0.020). Physical loads were more often present in
home than community-based falls (p=0.027). CONCLUSION: Falls that occur in the
community typically affect people with earlier PD and less severe disease than
home-based falls. Individuals experiencing community-based falls may benefit from
physiotherapy to manage challenging environments and high attention demands.
PMID- 28419874
TI - Oral administration of a specific kynurenic acid synthesis (KAT II) inhibitor
attenuates evoked glutamate release in rat prefrontal cortex.
AB - Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict
patient outcome; however, they remain poorly treated by current antipsychotic
drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative
allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are
commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ.
When acutely or chronically elevated in rodents, KYNA produces cognitive deficits
similar to those seen in the disease, making down-regulation of KYNA, via
inhibition of kynurenine aminotransferase II (KAT II), a potential treatment
strategy. We determined, in adult Wistar rats, if the orally available KAT II
inhibitor BFF816 a) prevents KYNA elevations in prefrontal cortex (PFC) after a
systemic kynurenine injection and b) reverses the kynurenine-induced attenuation
of evoked prefrontal glutamate release caused by stimulation of the nucleus
accumbens shell (NAcSh). Systemic injection of kynurenine (25 or 100 mg/kg, i.p.)
increased KYNA levels in PFC (532% and 1104% of baseline, respectively). NMDA
infusions (0.15 MUg/0.5 MUL) into NAcSh raised prefrontal glutamate levels more
than 30-fold above baseline. The two doses of kynurenine reduced evoked glutamate
release in PFC (by 43% and 94%, respectively, compared to NMDA alone). Co
administration of BFF816 (30 or 100 mg/kg, p.o.) with kynurenine (25 mg/kg, i.p.)
attenuated the neosynthesis of KYNA and dose-dependently restored NMDA-stimulated
glutamate release in the PFC (16% and 69%, respectively). The ability to prevent
KYNA neosynthesis and to normalize evoked glutamate release in PFC justifies
further development of KAT II inhibitors for the treatment of cognitive deficits
in SZ.
PMID- 28419876
TI - Reproducibility of the Balance Evaluation Systems Test (BESTest) and the Mini
BESTest in school-aged children.
AB - This study evaluated the intra-rater, inter-rater and test-retest reproducibility
of the Full-BESTest and Mini-BESTest when assessing postural control in children.
Thirty-four children aged 7-17 years participated in intra-rater and inter-rater
evaluation, and 22 children repeated assessment six weeks later for evaluation of
test-retest reliability. Postural control was assessed using the Full Balance
Evaluation Systems Test (Full-BESTest) and the short-form Mini-BESTest. Intra
rater, inter-rater and test-retest reproducibility were examined using video
assessment. Test-retest reproducibility was also assessed in real-time.
Reproducibility was examined by agreement and reliability statistics. Agreement
was calculated using percentage of agreement, Limits of Agreement and Smallest
Detectable Change. Reliability was calculated using Intra-class Correlation
Coefficients. Results showed that the reliability of Total Scores was excellent
for the Full-BESTest for all conditions (all ICCs>0.82), whereas the Mini-BESTest
ranged from fair to excellent (ICC=0.56-0.86). Percentage of Domain Scores with
good-excellent reliability (ICCs>0.60) was slightly higher for the Full-BESTest
(66%) compared to the Mini-BESTest (59%). Smallest Detectable Change scores were
good to excellent for the Full-BESTest (2%-6%) and for the Mini-BESTest (5%-10%)
relative to total test scores. Both the Full-BESTest and Mini-BESTest can
discriminate postural control abilities within and between days in school-aged
children. The Full-BESTest has slightly better reproducibility and a broader
range of items, which could be the most useful version for treatment planning. We
propose minor modifications to improve reproducibility for children, and indicate
the modified version by the title Kids-BESTest. Future psychometric research is
recommended for specific paediatric clinical populations.
PMID- 28419877
TI - Effect of foot orthoses on the medial longitudinal arch in children with flexible
flatfoot deformity: A three-dimensional moment analysis.
AB - Foot orthoses are often used to correct altered gait patterns. The purpose of
this study was to investigate how foot orthoses can modify the magnitude of three
dimensional moments of ankle, knee, and hip joints during a stride of gait in
children with flexible flat feet. Bilateral gait data were collected from
fourteen male children (age 10.2+/-1.4 years) suffering from flat feet syndrome.
In order to obtain the kinematics data, a Vicon system with six cameras (100Hz)
was used and two Kistler force plates (1000Hz) to record the kinetics data under
each leg. Arc support foot orthoses were used as an intervention. Paired-sample T
test was used for within-group comparisons (alpha=0.05). The results of data
analysis showed that foot orthoses can decrease the ankle evertor moment, knee
and hip abductor moments and hip flexor moment in dominant lower limb. In non
dominant lower limb, using the orthoses can decrease evertor and internal rotator
moments at the ankle, flexor and internal rotator moments at the knee and
extensor moment at the hip, while it can increase dorsiflexor moment at the
ankle. The findings imply that effects of orthoses on three dimensional moments
differ in dominant and non-dominant lower limbs. Furthermore, results
demonstrated that dominant and non-dominant lower limbs would also show different
responses to the same intervention.
PMID- 28419878
TI - Effect of Gross Total Resection in World Health Organization Grade II
Astrocytomas: SEER-Based Survival Analysis.
AB - INTRODUCTION: We sought to compare the survival benefit associated with gross
total resection (GTR) in World Health Organization grade II astrocytomas (A2)
with those of grade III (A3) and grade IV (glioblastoma) astrocytomas. METHODS:
Using the Surveillance, Epidemiology, and End Results program database (1999
2010), we identified 4113 A2 patients. Surgical resection was defined as GTR,
subtotal resection (STR), or no resection. Kaplan-Meier and multivariate Cox
proportional hazards analyses were used to assess survival with respect to extent
of resection. Results were compared with the benefit of GTR over STR in 2755 A3
and 21,962 glioblastoma patients from the same database. RESULTS: A multivariate
Cox proportional hazards analysis indicated that A2 patients who underwent a GTR
had a 28.3% reduction in the hazard of death relative to A2 patients who
underwent STR. Similar risk reductions were observed in A2 patients age <50 and
>=50. However, because of differences in the natural history of these cohorts,
the relative hazard reduction translated into distinct overall survival profiles.
For A2 patients >=50 years old, the GTR-associated survival benefit was
approximately 6 months, resembling that observed in glioblastoma patients. In
contrast, GTR in A2 patients <50 years old was associated with survival profiles
superior to those observed in A3 patients. CONCLUSIONS: In the Surveillance,
Epidemiology, and End Results (SEER) program database, GTR-associated survival
benefit in A2 patients >=50 years old resembled that observed in glioblastoma,
while GTR in A2 patients <50 years old was associated with a distinctly more
favorable survival profile.
PMID- 28419879
TI - Challenging the Myth of Right Nondominant Hemisphere: Lessons from
Corticosubcortical Stimulation Mapping in Awake Surgery and Surgical
Implications.
AB - For many years, the right hemisphere (RH) was considered as nondominant,
especially in right-handers. In neurosurgical practice, this dogma resulted in
the selection of awake procedure with language mapping only for lesions of the
left dominant hemisphere. Conversely, surgery under general anesthesia (possibly
with motor mapping) was usually proposed for right lesions. However, when
objective neuropsychological assessments were performed, they frequently showed
cognitive and behavioral deficits after brain surgery, even in the RH. Therefore,
to preserve an optimal quality of life, especially in patients with a long
survival expectancy (as in low-grade gliomas), awake surgery with cortical and
axonal electrostimulation mapping has recently been proposed for resection of
right tumors. Here, we review new insights gained from intraoperative stimulation
into the pivotal role of the RH in movement execution and control, visual
processes and spatial cognition, language and nonverbal semantic processing,
executive functions (e.g., attention), and social cognition (mentalizing and
emotion recognition). These original findings, which break with the myth of a
nondominant RH, may have important implications in cognitive neurosciences, by
improving our knowledge of the functional connectivity of the RH, as well as for
the clinical management of patients with a right lesion. In brain surgery, awake
mapping should be considered more systematically in the RH. Moreover,
neuropsychological examination must be achieved in a more systematic manner
before and after surgery within the RH, to optimize care by predicting the
likelihood of functional recovery and by elaborating specific programs of
rehabilitation.
PMID- 28419880
TI - Trepanation Practices in Asclepieia: Systematizing a Neurosurgical Innovation.
AB - BACKGROUND: As ancient Greeks started looking for deities that could fulfill the
pragmatic needs of common people, local heroes started being mythologized and
worshipped through cults. METHODS: The most widespread such example was
Asclepius, possibly a skilled war surgeon who followed military expeditions to
Colchis and Troy. Our study investigates the possibility of the early
neurosurgery to have been started inside Asclepieia by Asclepius and his
followers. RESULTS: Asclepius was worshipped at religious temples called
Asclepieia where certain specific medical and surgical techniques were followed.
The most advanced technique was skull trepanation, which was most likely done as
an acute operation to release intracranial pressure. The contemporary Hippocratic
corpus provided extensive descriptions of the technique, and archaeologic
evidence has shown that many patients survived the operation. CONCLUSIONS:
Decompressive craniectomy techniques have been practiced for millennia but it is
possible that they were first systematized as a neurosurgical innovation through
the Ancient Greek religious cult followed in Asclepieia.
PMID- 28419881
TI - The Effects of Clinical Factors and Retro-Odontoid Soft Tissue Thickness on
Atlantoaxial Instability in Patients with Rheumatoid Arthritis.
AB - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that often occurs
in the atlantoaxial segment of the cervical spine and results in instability that
can cause severe pain and neurologic symptoms. Thickening of soft tissue
posterior to the odontoid process of the atlantoaxial segment is referred to as
retro-odontoid soft tissue (ROST) thickness or pseudotumor. The mechanism of ROST
thickness is still unknown. METHODS: Among patients diagnosed with RA, those with
cervical radiographs and magnetic resonance imaging records were selected for
investigation of their clinical symptoms, laboratory findings, radiologic
evaluation, and RA medication history. RESULTS: A total of 199 patients were
selected and divided into lower and upper median groups according to the ROST
thickness value. In patients with RA, the median ROST thickness value was 2.3 mm
(interquartile range, 1.4-3.4). The median value of the anterior atlanto-dens
interval (ADI) was 2.4 mm, with a significant difference being observed between
the lower and upper median ROST thickness groups (P = 0.001). Multivariable
linear regression analysis revealed a correlation between Steinbrocker stage and
the positivity of rheumatoid factor. For each unit increase in the Steinbrocker
stage, the ROST thickness increased by 0.35 mm (beta, -0.349; 95% confidence
interval -0.643 to -0.055; P = 0.020). For every 1-mm increase in the ADI, ROST
thickness decreased by 0.16 mm (beta, -0.163; 95% confidence interval -0.264 to
0.062; P = 0.002). CONCLUSIONS: This study showed a statistical correlation
between ROST thickness and ADI related to biomechanical changes in the dynamic
atlantoaxial segment, thereby suggesting the value of a prospective study.
PMID- 28419882
TI - Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a
Chinese girl with Fanconi Anemia.
AB - Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known
complement groups caused by mutations in different genes. FA complementation
group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant
variants in the FANCL gene were documented. Phenotype and genotype correlation in
FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L
caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in
the FANCL gene. The patient's clinical course was typical for FA with progression
to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at
9 years of age. Mutation analysis also detected a likely somatic c.2608G > A
(p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and
gains of 3q and 21q and accumulated non-clonal single cell chromosomal
abnormalities were detected in blood leukocytes as her FA progressed. This is the
first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene
mutation and copy number aberrations could be used to monitor disease progression
and the clinical findings provide further information for genotype-phenotype
correlation for FA-L.
PMID- 28419883
TI - Feasibility and safety of foam sclerotherapy followed by a multiple
subcutaneously interrupt ligation under local anaesthesia for outpatients with
varicose veins.
AB - PURPOSE: To prospectively evaluate the feasibility and safety of foam
sclerotherapy and ligation (FSL) for outpatients with varicose veins under local
anaesthesia. METHODS: 136 outpatients with varicose veins who were unwilling to
be hospitalized underwent FSL. FSL is a technique in which the dilated varicose
veins were ligated subcutaneously after foam sclerotherapy with an absorbable
suture. Patients were reviewed at 1, 3, 6 and 12 months after FSL. Pain scores
were recorded after FSL. The revised venous clinical severity scorer (rVCSS) and
clinical, etiological, anatomical, and pathological classification (CEAP) were
used to evaluate the improvement at 3 months after treatment. RESULTS: 146 limbs
in 136 outpatients with varicose veins were managed with FSL. The pain scores
decreased following FSL, CEAP classification score, the rVCSS values improved 3
months postintervention. No significant postoperative complications were observed
on follow-up. CONCLUSION: FSL is feasible, safe and easily to perform under local
anaesthesia for outpatients with varicose veins.
PMID- 28419884
TI - Fish oil supplementation for primary prevention of atrial fibrillation after
coronary artery bypass graft surgery: A randomized clinical trial.
AB - BACKGROUND: Atrial fibrillation (AF) after cardiac surgery is a common
complication that may influence patients' early and long term outcomes and
hospital costs. The purpose of this study was to assess the effect of fish oil on
occurrence of AF following coronary artery bypass graft surgery (CABG). METHODS:
This study was a single-center, randomized, double blinded, placebo-controlled
clinical trial. Four-hundred and one patients undergoing coronary artery bypass
graft surgery were randomly assigned to receive 2 g/d fish oil or placebo (olive
oil) for at least 5 days before surgery. The primary end point was defined as
time to AF improvement After AF incidence following isolated CABG or a need for
pharmacologic therapy or cardioversion. RESULTS: The time to AF improvement in
intervention group was shorter than control group (HR: 2.05; 95% CI = 0.70-6.22,
P = 0.20). The incidence of AF in the intervention and control groups was 8.40%
vs. 14.07% respectively (p = 0.07). Mean total duration of AF was 20.96 +/- 4.71
h in intervention groups and 46.87 +/- 7.44 h in control groups (p = 0.04). Mean
duration of stay in the ICU and total hospital stay showed a significant
reduction in the intervention group (p = 0.003 and p = 0.04, respectively).
CONCLUSION: The consumption of PUFA leads to a shorter time to AF improvement,
which was not statistically significant. The incidence of AF in patients
undergoing CABG surgery was decreased by approximately 5.7%; which was
statistically on the borderline. Fish oil reduced median length of stay in the
ICU and hospital. Further well-designed studies are needed to overcome the
limitations of the existing trials and provide conclusive conclusions.
PMID- 28419885
TI - Registry of implants for the reconstruction of pelvic floor in males and females:
A feasibility case series.
AB - INTRODUCTION: Most aspects of implant-assisted reconstruction of pelvic floor in
males and females are under debate and the research is not standardized.
Registries are supposed to shed light to the indications, surgical techniques and
material properties and to establish a standardized evaluation. METHODS: A
working group was formed to create an online platform for registration and
outcome measurement of implant-assisted operations for pelvic organ prolapse
(POP) and female and male stress urinary incontinence (SUI). 20 patients with
modified mesh materials were evaluated over 23 months follow up in the registry
to prove the feasibility of the registry. For validation a previously published
modified "satisfaction, anatomy, continence, safety - S.(A.)C.S score" was used.
RESULTS: A consensus was met on definitions and classifications of patient
variables, surgical procedures and implants, as well as outcome parameters
(efficacy, continence, satisfaction, complications). Different subgroup modules
were formed in accordance with treated condition. The maximum score of cure was
reached by 25-100% of patients depending on the indication. CONCLUSION: A
prospective registry in accordance with IDEAL-D framework is justified for the
evaluation and regulation of implants for pelvic floor reconstruction.
PMID- 28419886
TI - Total hip arthroplasty for patients with Crowe type IV developmental dysplasia of
the hip: Ten years results.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the rate of
union, functional results and complications in patients with Crowe IV
developmental dysplasia of the hip (DDH) who underwent cementless total hip
arthroplasty (THA) with S-ROM prostheses and subtrochanteric transverse
shortening osteotomy. METHODS: Forty-five patients (52 hips) operated between
January 2005 and May 2008, with a mean age of 40.6 years at surgery were
followed. The mean follow-up period was 9.8 years. Clinical outcomes,
radiographic outcomes and complications were evaluated. RESULTS: Osteotomy union
occurred in 52 of 52 femurs (100%). Mean Harris hip score improved from 33.7 +/-
4.7 preoperatively to 81.2 +/- 6.3, 90.8 +/- 5.3 and 89.8 +/- 7.1 at 1, 5 and 10
years postoperatively. Two patients had temporary sciatic nerve paralysis
postoperatively, and 2 patients experienced early postoperative dislocation. Two
patients complained about mild longer limb length than the non-operated limb at
the last follow-up. Three hips showed osteolysis in Gruen zone 1, and 1 hip
showed osteolysis in zone 1 and 7. No implants were revised, and no signs of
component loosening and migration were observed at the last follow-up visit.
CONCLUSIONS: S-ROM stem combined with transverse subtrochanteric shortening
osteotomy in THA for patients with Crowe type IV DDH has good clinical results
with small risk of complications.
PMID- 28419887
TI - Unpacking the impact of adverse childhood experiences on adult mental health.
AB - Exposure to childhood adversity has an impact on adult mental health, increasing
the risk for depression and suicide. Associations between Adverse Childhood
Experiences (ACEs) and several adult mental and behavioral health outcomes are
well documented in the literature, establishing the need for prevention. The
current study analyzes the relationship between an expanded ACE score that
includes being spanked as a child and adult mental health outcomes by examining
each ACE separately to determine the contribution of each ACE. Data were drawn
from Wave II of the CDC-Kaiser ACE Study, consisting of 7465 adult members of
Kaiser Permanente in southern California. Dichotomous variables corresponding to
each of the 11 ACE categories were created, with ACE score ranging from 0 to 11
corresponding to the total number of ACEs experienced. Multiple logistic
regression modeling was used to examine the relationship between ACEs and adult
mental health outcomes adjusting for sociodemographic covariates. Results
indicated a graded dose-response relationship between the expanded ACE score and
the likelihood of moderate to heavy drinking, drug use, depressed affect, and
suicide attempts in adulthood. In the adjusted models, being spanked as a child
was significantly associated with all self-reported mental health outcomes. Over
80% of the sample reported exposure to at least one ACE, signifying the potential
to capture experiences not previously considered by traditional ACE indices. The
findings highlight the importance of examining both cumulative ACE scores and
individual ACEs on adult health outcomes to better understand key risk and
protective factors for future prevention efforts.
PMID- 28419888
TI - Zika, sexual transmission and prudent public health policy.
PMID- 28419889
TI - Studies on the 6-homologation of beta-D-idopyranosides.
AB - beta-D-Idopyranosides are interesting sugars because of their unusual
conformational flexibility in the pyranosyl ring, and also their beta-1,2-cis
anomeric configuration. Here we report our studies of the regioselective opening
of 4,6-O-benzylidene-protected beta-D-idopyranosides under reducing conditions,
and the subsequent 6-homologation via Swern oxidation and Wittig olefination to
afford a 6,7-dideoxy-beta-D-ido-hept-6-enopyranoside. This olefination product
was found to adopt predominantly 1C4 conformation in solution by NMR experiments,
which places the vinyl group at a more sterically hindered axial position and
creates difficulty in subsequent hydroborations.
PMID- 28419890
TI - Pragmatic trial of a Study Navigator Model (NAU) vs. Ambassador Model (N+) to
increase enrollment to health research among community members who use illicit
drugs.
AB - BACKGROUND: Although drug use is common in the population, drug users are
sometimes excluded from research without justification. Two models of
individualized study matching were compared for effectiveness in enrolling people
who "endorsed current drug use" and those who "did not" into appropriate
research. METHODS: Participants in the NIDA-funded Transformative Approach to
Reduce Research Disparities Towards Drug Users study (Navigation Study) were
recruited through a Clinical and Translational Science Award (CTSA) community
engagement model. Of the 614 community-recruited adults, 326 endorsed current
drug use (cases); 288 did not (controls). Participants were randomized to one of
two intervention groups: Navigation as Usual (NAU) [individualized study matching
through a Study Navigator] or Enhanced Navigation (N+) [individualized study
matching plus transportation and other assistance through an Ambassador]. Rates
of enrollment into research studies were compared. RESULTS: At 90 days, N+ vs.
the NAU intervention was associated with higher enrollment among both drug users
(36.0% N+ vs. 24.9% NAU) and non-drug users (45.5% N+ vs. 25.2% NAU). NAU
attained the same rate of enrollment for users of drugs (24.9%) and non-users
(25.2%); N+ had similar rates as well (36.0% drug users vs. 45.5% non-drug
users). In addition, high rates of enrollment were achieved among all groups of
participants, from 24.9% (drug users in NAU) to 45.5% (non-drug users in N+).
CONCLUSIONS: Both the NAU and N+ methods can reduce barriers and help users and
non-users become part of the population that participates in research. Working
with the local CTSA adds significant value to the research enterprise.
PMID- 28419891
TI - I care, even after the first impression: Facial appearance-based evaluations in
healthcare context.
AB - PURPOSE: Prior research has demonstrated that healthcare providers' implicit
biases may contribute to healthcare disparities. Independent research in social
psychology indicates that facial appearance-based evaluations affect social
behavior in a variety of domains, influencing political, legal, and economic
decisions. Whether and to what extent these evaluations influence approach
behavior in healthcare contexts warrants research attention. Here we investigate
the impact of facial appearance-based evaluations of trustworthiness on
healthcare providers' caring inclination, and the moderating role of experience
and information about the social identity of the faces. METHOD: Novice and expert
nurses rated their inclination to provide care when viewing photos of trustworthy
, neutral-, and untrustworthy-looking faces. To explore whether information about
the target of care influences caring inclination, some participants were told
that they would view patients' faces while others received no information about
the faces. RESULTS: Both novice and expert nurses had higher caring inclination
scores for trustworthy-than for untrustworthy-looking faces; however, experts had
higher scores than novices for untrustworthy-looking faces. Regardless of a
face's trustworthiness level, experts had higher caring inclination scores for
patients than for unidentified individuals, while novices showed no differences.
CONCLUSIONS: Facial appearance-based inferences can bias caring inclination in
healthcare contexts. However, expert healthcare providers are less biased by
these inferences and more sensitive to information about the target of care.
These findings highlight the importance of promoting novice healthcare
professionals' awareness of first impression biases.
PMID- 28419892
TI - Plasma apolipoproteins and physical and cognitive health in very old individuals.
AB - Apolipoproteins play a crucial role in lipid metabolism with implications in
cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We
quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using
immunoassays and explored relationships with APOE polymorphism epsilon2/3/4,
vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH,
and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends.
Centenarians had the highest ApoE levels and the lowest frequency of APOE
epsilon4 allele relative to younger groups. Apolipoprotein levels trended lower
in APOE epsilon4 homozygotes and heterozygotes compared with noncarriers, with
ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except
ApoH were higher in females. Sex- and age-related differences were apparent in
the association of apolipoproteins with cognitive performance, as only women had
significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life,
whereas associations at older age were nonsignificant or positive. Our findings
suggest levels of some apolipoproteins, especially ApoE, are associated with
lifespan and cognitive function in exceptionally long-lived individuals.
PMID- 28419893
TI - Carbon monoxide-related fatalities: A 60-year single institution experience.
AB - OBJECTIVE: Though carbon monoxide (CO) poisonings account currently for a
relatively small percentage of total non-natural deaths in Europe, they represent
a serious public health burden and significant component of avoidable mortality
in many countries. Our aim was to investigate long-term trends and to determine
epidemiologic characteristics of the CO-related deaths in the Czech Republic,
recorded at the Department of Forensic Medicine in Hradec Kralove. METHODS: This
was an autopsy-based single-centre retrospective cohort study of all fatalities
caused by CO poisoning over six decades (1947-2006). All data were numerically
evaluated and processed using NCSS 10 Statistical Software. Statistical
significance was defined as a p-value less than 0.05. RESULTS: A total of 1233 CO
related deaths were identified for inclusion in the study. The manner of death
was ranked in order as follows: 45% accidental poisoning, 40% suicidal poisoning,
1% homicidal poisoning, 14% remained undetermined. There were slightly more male
victims (59%) than female, and the mean age overall was 48 years. The majority of
CO-related fatalities were attributed to coal gas inhalation, with the remainder
being from inhaled motor vehicle exhaust fumes, inhaled fire smoke, and other
combustion sources such as charcoal, gas and wood-burning appliances. The mean
blood carboxyhemoglobin (COHb) level was 66%. A positive blood ethanol
concentration was measured in 455 (37%) cases examined. Non-intentional
poisonings were highly correlated with the winter months. CONCLUSION: This study
shows that the prevalence of CO-related deaths has decreased significantly in the
Czech Republic following the widespread detoxification of the domestic gas in the
1990-1995. Our findings suggest that acute ethanol use, poorer socioeconomic
position, and inadequate education status about the danger of CO are associated
with an increased risk of fatal CO poisoning. Finally, our results demonstrate
the continued value of the autopsy in monitoring global public health security
issues and socioeconomic situation. Further similar large-scale studies in
different populations are needed to improve the targeting of interventions to the
groups with the highest level of risk, and to understand the sources of variation
in CO-related mortality.
PMID- 28419895
TI - Electrochemical oxidation of iron and alkalinity generation for efficient sulfide
control in sewers.
AB - The addition of iron salts is one of the most commonly used dosing strategies for
sulfide control in sewers. However, iron salts decrease the sewage pH which not
only reduces the effectiveness of sulfide precipitation but also enhances the
release of residual sulfide to the sewer atmosphere. Equally important,
concentrated iron salt solutions are corrosive and their frequent transport,
handling, and on-site storage often come with Occupational Health and Safety
(OH&S) concerns. Here, we experimentally demonstrated a novel sulfide control
approach using electrochemical systems with parallel placed iron electrodes. This
enabled combining anodic dissolved iron species release with cathodic hydroxyl
anion production, which alleviates all the aforementioned concerns. A long-term
experiment was successfully carried out achieving an average sulfide removal
efficiency of 95.4 +/- 4.4% at low voltage input of 2.90 +/- 0.54 V over the
course of 8 weeks. This electrochemical method was demonstrated to successfully
achieve efficient sulfide control. In addition, it increases the sewage pH,
thereby overcoming the drawbacks associated with the pH decrease in the case of
conventional iron salt dosing. Ferrous ions were produced at an overall coulombic
efficiency (CE) of 98.2 +/- 1.2%, whereas oxygen evolution and direct sulfide
oxidation were not observed. Short-term experiments showed that increasing either
inter-electrode gap or current density increased the cell voltage associated with
the increase in the ohmic drop of the system. Overall, this study highlights the
practical potential of in-situ generation of dissolved iron species and
simultaneous hydroxyl anion generation for efficient sulfide control in sewers.
PMID- 28419896
TI - The use of diatoms in ecotoxicology and bioassessment: Insights, advances and
challenges.
AB - Diatoms are regularly used for bioassessment and ecotoxicological studies in
relation to environmental and anthropogenic disturbances. Traditional taxonomical
diatom parameters (cell counts, biovolume estimates, species richness, diversity
indices and metrics using sensitive and tolerant diatom species) are regularly
used for these studies. In the same context, very less focus was given on new
endpoints of diatoms (life-forms, nuclear anomalies, alteration in photosynthetic
apparatus shape, motility, lipid bodies, size reduction and deformities), in
spite of their numerous merits, such as, their easiness, quickness, cheapness,
global acceptation and no especial training in diatom taxonomy. In this review we
analyzed 202 articles (from lab and field studies), with the aim to investigate
the bioassessment and ecotoxicological advancement taken place in diatom research
especially in terms of exploring new endpoints along with the traditional
taxonomical parameters in a perspective which can greatly enhance the evaluation
of fluvial ecosystem quality for biomonitoring practices.
PMID- 28419897
TI - Nurse mentor perceptions in the delivery of a home-based cardiac rehabilitation
program to support patients living in rural areas: An interpretive study.
AB - Home-based cardiac rehabilitation (CR) programs improve health outcomes for
people diagnosed with heart disease. Mentoring of patients by nurses trained in
CR has been proposed as an innovative model of cardiac care. Little is known
however, about the experience of mentors facilitating such programs and adapting
to this new role. The aim of this qualitative study was to explore nurse mentor
perceptions of their role in the delivery of a home-based CR program for rural
patients unable to attend a hospital or outpatient CR program. Seven nurses
mentored patients by telephone providing patients with education, psychosocial
support and lifestyle advice during their recovery. An open-ended survey was
administered to mentors by email and findings revealed mentors perceived their
role to be integral to the success of the program. Nurses were satisfied with the
development of their new role as patient mentors. They believed their
collaborative skills, knowledge and experience in coronary care, timely support
and guidance of patients during their recovery and use of innovative audiovisual
resources improved the health outcomes of patients not able to attend traditional
programs. Cardiac nurses in this study perceived that they were able to
successfully transition from their normal work practices in hospital to mentoring
patients in their homes.
PMID- 28419894
TI - Muscle cell communication in development and repair.
AB - Under basal conditions, postnatal skeletal muscle displays little cell turnover.
With injury, muscle initiates a rapid repair response to reseal damaged membrane,
reactivating many developmental pathways to facilitate muscle regeneration and
prevent tissue loss. Muscle precursor cells become activated accompanied by
differentiation and fusion during both muscle growth and regeneration; inter
cellular communication is required for successful completion of these processes.
Cellular communication is mediated by lipids, fusogenic membrane proteins, and
exosomes. Muscle-derived exosomes carry proteins and micro RNAs as cargo.
Secreted factors such as IGF-1, TGFbeta, and myostatin are also released by
muscle cells providing local signaling cues to modulate muscle fusion and
regeneration. Proteins that regulate myoblast fusion also participate in membrane
repair and regeneration. Here we will review methods of muscle cell communication
focusing on proteins that mediate membrane fusion, exosomes, and autocrine
factors.
PMID- 28419898
TI - Theory-guided access to efficient photodegradation of the simplest
perfluorocarboxylic acid: Trifluoroacetic acid.
AB - The photodegradation approaches of perfluorocarboxylic acids have attracted
considerable attention and have been developed extensively. However, the reaction
channels along which the perfluorocarboxylic acid molecules dissociate remain to
be deciphered by means of the quantum chemical method at the electronically
excited state level of theory until now. Here we report the photodissociation
mechanism of the simplest perfluorocarboxylic acid, trifluoroacetic acid, using
the complete active space self-consistent field (CASSCF) and the multi
configurational second-order perturbation (CASPT2) methods. The CC and CO alpha
bond fission channels were both taken into account. Based on the constructed
potential energy surfaces, it is concluded that the CC alpha bond fission, which
would probably account for further degradations and mineralizations, may mainly
take place in the triplet manifolds via intersystem crossing from the S1 state.
Thus, taking the computational results of the simple member of
perfluorocarboxylic acids as a rational clue, strategies to enhance intersystem
crossing process efficiencies of the photodegradation of perfluorocarboxylic
acids can be developed.
PMID- 28419899
TI - The long term tsunami impact: Evolution of iron speciation and major elements
concentration in tsunami deposits from Thailand.
AB - The article describes the unique studies of the chemical composition changes of
new geological object (tsunami deposits in south Thailand - Andaman Sea Coast)
during four years (2005-2008) from the beginning of formation of it (deposition
of tsunami transported material, 26 December 2004). The chemical composition of
the acid leachable fraction of the tsunami deposits has been studied in the scope
of concentration macrocompounds - concentration of calcium, magnesium, iron,
manganese and iron speciation - the occurrence of Fe(II), Fe(III) and non-ionic
iron species described as complexed iron (Fe complex). The changes of chemical
composition and iron speciation in the acid leachable fraction of tsunami
deposits have been observed with not clear tendencies of changes direction. For
iron speciation changes the transformation of the Fe complex to Fe(III) has been
recorded with no significant changes of the level of Fe(II).
PMID- 28419900
TI - Dimethylarsenate (DMA) exposure influences germination rates, arsenic uptake and
arsenic species formation in wheat.
AB - The contamination of cereals with arsenic (As) is a global health and agronomic
concern. This study compared the physiological response, As uptake and As
speciation in the grains and above ground tissues of 20 wheat cultivars exposed
to 5 mg As kg-1 soil as either arsenate (AsV) or dimethylarsenate (DMA) under
glasshouse conditions. Germination rates for the majority of cultivars exceeded
80% for the majority of cultivars when exposed to AsV, but fell significantly to
20-40% when exposed to DMA. For a number of cultivars, grain yields were 20-50%
lower when plants were exposed to DMA compared to AsV. Grain As concentrations
were between 0.6 and 1.6 MUg As g-1 grain across the twenty cultivars when
exposed to AsV, whereas grain As concentrations were much higher (2.2-4.6 MUg As
g-1 grain) when exposed to DMA. When plants were exposed to AsV, 100% of the As
present in the grain was found as inorganic As while in plants exposed to DMA, 70
90% of As was present as DMA with the remainder found as inorganic As. DMA is
believed to be incorporated by plants via silica (Si) acid channels and
assessment of grain Si concentrations demonstrated that up to 40% less Si was
accumulated in grains when plants were exposed to DMA. The decreased germination
rates and grain yields in the presence of DMA is similar to the symptoms
described for straight head disease in rice, which has been linked to DMA
exposure. The results presented here indicate some analogous processes occur in
wheat to those described in rice. We hypothesise that exposure to DMA may have
inhibited Si-metabolism and translocation which resulted in both developmental
impairment and possibly an increased susceptibility to soil pathogens.
PMID- 28419901
TI - Does exclusion of cancers registered only from death-certificate information
diminish socio-demographic disparities in recorded survival?
AB - BACKGROUND: Death Certificate Only (DCO) cancer cases are commonly excluded from
survival analyses due to unknown survival time. This study examines whether socio
demographic factors are associated with DCO diagnosis, and the potential effects
of excluding DCO cases on socio-demographic cancer survival disparities in NSW,
Australia. METHODS: NSW Cancer Registry data for cases diagnosed in 2000-2008
were used in this study. Logistic regression was used to estimate the odds of DCO
registration by socio-demographic sub-group (socio-economic disadvantage,
residential remoteness, country of birth, age at diagnosis). Cox proportional
hazard regression was used to estimate the probability of death from cancer by
socio-demographic subgroup when DCO cases were included and excluded from
analyses. RESULTS: DCO cases consisted of 1.5% (n=4336) of all cases (n=299,651).
DCO diagnosis was associated with living in socio-economically disadvantaged
areas (most disadvantaged compared with least disadvantaged quintile: odds ratio
OR 1.25, 95%CI 1.12-1.40), living in inner regional (OR 1.16, 95%CI 1.08-1.25) or
remote areas (OR 1.48, 95%CI 1.01-2.19), having an unknown country of birth (OR
1.63, 95%CI 1.47-1.81) and older age. Including or excluding DCO cases had no
significant impact on hazard ratios for cancer death by socio-economic
disadvantage quintile or remoteness category, and only a minor impact on hazard
ratios by age. CONCLUSION: Socio-demographic factors were associated with DCO
diagnosis in NSW. However, socio-demographic cancer survival disparities remained
unchanged or varied only slightly irrespective of including/excluding DCO cases.
Further research could examine the upper limits of DCO proportions that
significantly alter estimated cancer survival differentials if DCOs are excluded.
PMID- 28419902
TI - Evaluating the efficacy of DNA differential extraction methods for sexual assault
evidence.
AB - Analysis of sexual assault evidence, often a mixture of spermatozoa and victim
epithelial cells, represents a significant portion of a forensic DNA laboratory's
case load. Successful genotyping of sperm DNA from these mixed cell samples,
particularly with low amounts of sperm, depends on maximizing sperm DNA recovery
and minimizing non-sperm DNA carryover. For evaluating the efficacy of the
differential extraction, we present a method which uses a Separation Potential
Ratio (SPRED) to consider both sperm DNA recovery and non-sperm DNA removal as
variables for determining separation efficiency. In addition, we describe how the
ratio of male-to-female DNA in the sperm fraction may be estimated by using the
SPRED of the differential extraction method in conjunction with the estimated
ratio of male-to-female DNA initially present on the mixed swab. This approach
may be useful for evaluating or modifying differential extraction methods, as we
demonstrate by comparing experimental results obtained from the traditional
differential extraction and the Erase Sperm Isolation Kit (PTC(c)) procedures.
PMID- 28419903
TI - DNA methylation-based age prediction from saliva: High age predictability by
combination of 7 CpG markers.
AB - DNA methylation is currently one of the most promising age-predictive biomarkers.
Many studies have reported DNA methylation-based age predictive models, but most
of these are based on DNA methylation patterns from blood. Only a few studies
have examined age-predictive DNA patterns in saliva, which is one of the most
frequently-encountered body fluids at crime scenes. In this study, we generated
genome-wide DNA methylation profiles of saliva from 54 individuals and identified
CpG markers that showed a high correlation between methylation and age. Because
the age-associated marker candidates from saliva differed from those of blood, we
investigated DNA methylation patterns of 6 age-associated CpG marker candidates
(cg00481951, cg19671120, cg14361627, cg08928145, cg12757011, and cg07547549 of
the SST, CNGA3, KLF14, TSSK6, TBR1, and SLC12A5 genes, respectively) in addition
to a cell type-specific CpG marker (cg18384097 of the PTPN7 gene) in an
independent set of saliva samples obtained from 226 individuals aged 18 to 65
years. Multiplex methylation SNaPshot reactions were used to generate the data.
We then generated a linear regression model with age information and the
methylation profile from the 113 training samples. The model exhibited a 94.5%
correlation between predicted and chronological age with a mean absolute
deviation (MAD) from chronological age of 3.13 years. In subsequent validation
using 113 test samples, we also observed a high correlation between predicted and
chronological age (Spearman's rho=0.952, MAD from chronological age=3.15years).
The model composed of 7 selected CpG sites enabled age prediction in saliva with
high accuracy, which will be useful in saliva analysis for investigative leads.
PMID- 28419904
TI - Leydig cell tumor in grey zone: A case report.
AB - INTRODUCTION: Leydig cell tumor constitutes only about 1-3% of testicular
neoplasms. There is apparently increased incidence in the last few years; one
possible explanation for this phenomenon is the widespread use of ultrasound
technology and the subsequent increased early detection of smaller lesions that
have not been found in historical series. CASE PRESENTATION: We report a case of
Leydig cell tumor of testis in a patient presenting with painless long standing
slowly growing left scrotal mass who found to have intrapulmonary nodule and
multiple enlarged retroperitoneal lymph nodes on staging work up. The mass was
managed by radical orchiectomy. Pathological diagnosis was Leydig cell tumor.
DISCUSSION: Orchiectomy is the accepted mode of treatment but follow-up every 3-6
months with physical examination, hormone assays, scrotal and abdominal
ultrasonography, chest radiography, and CT scans is essential in such a case with
a potential for malignant behavior. CONCLUSION: Inguinal orchiectomy is the
therapeutic decision of choice and long-term follow-up is necessary to exclude
recurrence or metastasis. Cases which fall in the grey zone like ours need to be
followed up carefully for metastasis instead of rushing into an early
retroperitoneal lymph node dissection, with its potential risks and
complications.
PMID- 28419905
TI - Spontaneous perforation of common bile duct in a young female: An intra-operative
surprise.
AB - INTRODUCTION: Spontaneous CBD perforation is one of the rare causes of acute
abdomen in infants and extremely rare in adults. It is rarely suspected and
correctly diagnosed preoperatively. PRESENTATION OF CASE: A 17year old female
presented to Emergency Department with sudden onset of pain and distention of
abdomen, associated with vomiting and non-passage of flatus and stool for 3days
and features of generalized peritonitis. On exploration, a perforation of size
0.5cm in diameter was present on the antero-lateral surface of supraduodenal part
of common bile duct (CBD) below the junction of cystic duct and common hepatic
duct. Cholecystectomy done and the CBD repaired over a T-tube. DISCUSSION:
Spontaneous perforation of bile duct should ideally manage with T-tube drainage
of the CBD along with cholecystectomy. In case with distal obstruction of the
CBD, a biliary enteric bypass should be done. CONCLUSION: Due to the paucity of
cases, the index of suspicion for this diagnosis is low. But bilious peritoneal
tap, features of generalized peritonitis and absence of free gas under diaphragm
in abdominal x-ray may be considered as clues for suspicion. Accordingly, Surgery
remains the mainstay of treatment.
PMID- 28419906
TI - Plant hormone signaling in flowering: An epigenetic point of view.
AB - Reproduction is one of the most important phases in an organism's lifecycle. In
the case of angiosperm plants, flowering provides the major developmental
transition from the vegetative to the reproductive stage, and requires genetic
and epigenetic reprogramming to ensure the success of seed production. Flowering
is regulated by a complex network of genes that integrate multiple environmental
cues and endogenous signals so that flowering occurs at the right time; hormone
regulation, signaling and homeostasis are very important in this process. Working
alone or in combination, hormones are able to promote flowering by epigenetic
regulation. Some plant hormones, such as gibberellins, jasmonic acid, abscisic
acid and auxins, have important effects on chromatin compaction mediated by DNA
methylation and histone posttranslational modifications, which hints at the role
that epigenetic regulation may play in flowering through hormone action. miRNAs
have been viewed as acting independently from DNA methylation and histone
modification, ignoring their potential to interact with hormone signaling -
including the signaling of auxins, gibberellins, ethylene, jasmonic acid,
salicylic acid and others - to regulate flowering. Therefore, in this review we
examine new findings about interactions between epigenetic mechanisms and key
players in hormone signaling to coordinate flowering.
PMID- 28419908
TI - Editorial overview: Characterizing the cancer genome: mechanistic insights and
translational opportunities.
PMID- 28419907
TI - FLC expression is down-regulated by cold treatment in Diplotaxis tenuifolia (wild
rocket), but flowering time is unaffected.
AB - Wild rocket (Diplotaxis tenuifolia) has become a very popular salad leaf due to
its peppery taste. It is part of the Brassicaceae family and thus has a high
level of homology at the DNA level to other Brassica species including
Arabidopsis thaliana. The vernalization and photoperiodic requirements of wild
rocket have not been reported to date. Photoperiodic experiments described here
demonstrate that rocket is a facultative long day plant. To investigate the
vernalization requirement, both seed and young plants were given vernalization
treatments at 4 degrees C for different lengths of time. A rocket homologue of
FLOWERING LOCUS C (DtFLC) was isolated and shown to functionally complement the
Arabidopsis FRI+flc3 null mutant. Whilst the expression of DtFLC was
significantly reduced after just one week of cold treatment, cold treatments of
two to eight weeks had no significant effect on bolting time of wild rocket
indicating that rocket does not have a vernalization requirement. These findings
illustrate that important fundamental differences can exist between model and
crop plant species, such as in this case where down-regulation of DtFLC
expression does not enable earlier flowering in wild rocket as it does in
Arabidopsis and many other Brassica species.
PMID- 28419909
TI - Reduction in advanced breast cancer after introduction of a mammography screening
program in Tyrol/Austria.
AB - BACKGROUND: We analysed all female breast cancer (BC) cases in Tyrol/Austria
regarding the shift in cancer characteristics, especially the shift in advanced
BC, for the group exposed to screening as compared to the group unexposed to
screening. METHODS: The analysis was based on all BC cases diagnosed in women
aged 40-69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The
data were linked to the Tyrolean mammography screening programme database to
classify BC cases as "exposed to screening" or "unexposed to screening". Age
adjusted relative risks (RR) were estimated by relating the exposed to the
unexposed group. RESULTS: In a total of about 145,000 women aged 40-69 years
living in Tyrol during the study period, 1475 invasive BC cases were registered.
We estimated an age-adjusted relative risk (RR) for tumour size >= 21 mm of 0.72
(95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI
0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing
those exposed to those unexposed to screening, respectively. CONCLUSION: In our
population-based registry analysis we observed that participation in the
mammography screening programme in Tyrol is associated with a 28% decrease in
risk for BC cases with tumour size >= 21 mm and a 17% decrease in risk for
advanced BC. We therefore expect the Tyrolean mammography programme to show a
reduction in BC mortality.
PMID- 28419910
TI - Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI.
AB - OBJECTIVE: To identify and estimate the importance of risk factors on pregnancy
loss until the end of the second trimester after clinical pregnancy was achieved
by either in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection
(ICSI). STUDY DESIGN: Retrospective cohort study including 588 cycles with fresh
embryo transfers and 150 cycles with frozen-thawed embryo transfers using
logistic regression. RESULTS: The rate of miscarriages subsequent to a fresh
embryo transfer was significantly increased by a diagnosis of endometriosis
(p=0.02), as well as significantly influenced by the age of the female patient at
the time of oocyte retrieval (p<0.01) and the serum level of testosterone
(p=0.02). The time between freezing and thawing of the pronuclear stages for a
frozen-thawed embryo transfer revealed a trend to a higher rate of miscarriages
(p=0.06). CONCLUSION: Endometriosis significantly decreases the chance of having
a baby even with IVF or ICSI.
PMID- 28419911
TI - Safety and long-term efficacy of fractional CO2 laser treatment in women
suffering from genitourinary syndrome of menopause.
AB - OBJECTIVES: To evaluate the safety and long-term efficacy of fractional CO2 laser
treatment in reducing the severity of symptoms of genitourinary syndrome of
menopause (GSM) in menopausal women. STUDY DESIGN: 102 women presenting with
symptomatic GSM were treated with the fractional CO2 laser (MonaLisa Touch, DEKA)
system across a series of treatments delivered at intervals of six or more weeks.
The Australian Pelvic Floor Questionnaire was used to gather data on sexual
function and side-effects at three time-points across the study period
(prospective panel design study). Wilcoxon signed-rank tests were used to detect
statistically and clinically significant changes in sexual function and side
effects occurring from pre- to post-treatment. The primary outcome of this study
was an improvement of the symptoms of GSM. The secondary outcome included bladder
function and prolapse symptoms. RESULTS: A total of 102 women suffering from
moderate to severe GSM were recruited. Eighty-four percent experienced
significant improvement in their symptoms after CO2 laser treatment. Scores on
measures of sexual function, dyspareunia, and bothersomeness of sexual issues
were improved from pre-treatment to long-term (12-24 month) follow-up.
Furthermore, there were improvements on measures of bladder function (P=0.001),
prolapse (P=0.001), vaginal sensation (P=0.001), vaginal lubrication (P<0.001)
and urge incontinence (P=0.003) from the pre-treatment assessment to the second
assessment (i.e. after the third treatment). CONCLUSIONS: In this study,
fractional microablative CO2 laser treatment was associated with an improvement
in symptoms of GSM and sexual function.
PMID- 28419912
TI - The mucosal pellicle - An underestimated factor in oral physiology.
AB - Bioadhesion and bio-adsorption of proteins, glycoproteins and other biomolecules
are ubiquitous phenomena in the oral cavity. While the protective role of the
adsorbed salivary biomolecules on teeth (the acquired enamel pellicle) is well
established, it has yet to be defined whether comparable processes occur on the
desquamating oral soft tissues. The general term for these layers is pellicle,
but due to the different characteristics of the coated surfaces the enamel
pellicle and mucosal pellicle are their own entities. There is considerable
information on the enamel pellicle, whereas only limited data are available on
the mucosal pellicle. This can be attributed to the difficult standardized
preparation of this biological structure. Based on the present knowledge the
abundant and characteristic components of the mucosal pellicle include secreted
soluble mucins (MUC5B, MUC7), membrane-associated epithelial mucins (MUC1), and
to a lesser degree CA VI, sIgA, and cystatin. However, it seems to be of
completely different ultrastructure as compared with the enamel pellicle. Since
it is comprised of larger glycoproteins retaining water, it might be considered
as a hydrogel, and it appears to have a lower tenacity than the enamel pellicle.
Maturation and turnover are influenced by the delivery of salivary proteins, by
the flow of saliva and the underlying desquamating oral epithelium. Its probable
functions include lubrication and moisture retention. In general, the mucosal
pellicle can be regarded as an underestimated key player in oral physiology.
PMID- 28419913
TI - Depression and anxiety both associate with serum level of hs-CRP: A gender
stratified analysis in a population-based study.
AB - BACKGROUND: Depression and anxiety are two important mood disorders that are
frequently associated with chronic diseases such as cardiovascular diseases
(CVDs). Hyper-inflammation is related to both CVDs and psychological conditions
such as depression and anxiety. Therefore, inflammation may partially explain the
relationship between depression and cardiovascular disease. OBJECTIVE: The
objective of this study was to perform a gender-stratified examination of the
association between symptoms of depression/anxiety disorders and serum hs-CRP and
inflammation linked conditions in a large Iranian population. METHODS: Symptoms
of depression and anxiety disorders and serum hs-CRP levels were measured in 9759
participants (40% males and 60% females) aged 35-65 years, enrolled in a
population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of
depression and anxiety were evaluated with Beck Depression and Anxiety
Inventories. According to the scores of depression and anxiety, individuals were
categorized into four groups of no or minimal, low, moderate and severe
categories. RESULTS: The median serum hs-CRP concentration increased with
increasing severity of depression and anxiety disorders. Male participants with
severe depression had significantly higher levels of hs-CRP (p<0.001); however,
this relationship was less marked among women (p=0.04). Subjects with severe
anxiety also had significantly higher levels of hs-CRP (p<0.001). Moreover, women
with severe depression and anxiety had higher BMI. There was also a positive
association between current smoking habit and depression/anxiety disorders.
CONCLUSION: Depression and anxiety disorders are associated with elevated levels
of hs-CRP, particularly among men. Also, there is a significant positive
association between depression/anxiety disorders and inflammation linked
conditions such as smoking and obesity; however, in the case of obesity this
association is only present in women.
PMID- 28419914
TI - Longitudinal changes in pubertal maturation and white matter microstructure.
AB - Emerging evidence in the field of adolescent neurodevelopment suggests that
pubertal processes may contribute to known trajectories of brain maturation, and
may contribute, in part, to sex differences in related cognitive, behavioral and
mental health outcomes. The current longitudinal study examined how changes in
physical pubertal maturation (measured by the Peterson Developmental Scale)
predict changes in white matter microstructure in 18 boys and 15 girls over an
approximate 2-year follow-up period, while accounting for age. Using Tract-Based
Spatial Statistics and multi-level modeling, the results showed that physical
pubertal changes predict patterns of changes in fractional anisotropy (FA) in
white matter regions in the thalamus, precentral gyrus, superior corona radiata,
corpus callosum (genu), superior corona radiata, and superior frontal gyrus. Sex
specific changes were also seen, as changes in gonadal and adrenal development
related to increases in FA in the superior frontal gyrus and precentral gyrus in
boys, but gonadal development related to decreases in FA in the anterior corona
radiata in girls. These findings are the first to show how changes over time in
pubertal development influence white matter development. In addition, they
support a larger body of emerging research suggesting that pubertal processes
contribute to distinct changes in boys and girls across brain development.
PMID- 28419916
TI - A sensitive label-free immunosensor for detection alpha-Fetoprotein in whole
blood based on anticoagulating magnetic nanoparticles.
AB - Accurate values of tumor markers in blood play an especially important role in
the diagnosis of illness. Here, based on the combination of three techniques
include anticoagulant technology, nanotechnology and biosensing technology, a
sensitive label-free immunosensor with anti-biofouling electrode for detection
alpha-Fetoprotein (AFP) in whole blood was developed by anticoagulating magnetic
nanoparticles. The obtained products of Fe3O4-E-PL-Hep nanoparticles were
characterized by fourier transform infrared (FT-IR) spectra, transmission
electron microscopy (TEM), zeta-potential and vibrating sample magnetometry
(VSM). Moreover, the blood compatibility of anticoagulating magnetic
nanoparticles was characterized by in vitro coagulation tests, hemolysis assay
and whole blood adhesion tests. Combining the anticoagulant property of heparin
(Hep) and the good magnetism of Fe3O4, the Fe3O4-E-PL-Hep nanoparticles could
improve not only the anti-biofouling property of the electrode surface when they
contact with whole blood, but also the stability and reproducibility of the
proposed immunosensor. Thus, the prepared anticoagulating magnetic nanoparticles
modified immunosensor for the detection of AFP showed excellent electrochemical
properties with a wide concentration range from 0.1 to 100ng/mL and a low
detection limit of 0.072ng/mL. Furthermore, five blood samples were assayed using
the developed immunosensor. The results showed satisfactory accuracy with low
relative errors. It indicated that our developed immunoassay was competitive and
could be potentially used for the detection of whole blood samples directly.
PMID- 28419915
TI - Enhanced imaging of lipid rich nanoparticles embedded in methylcellulose films
for transmission electron microscopy using mixtures of heavy metals.
AB - Synthetic and naturally occurring lipid-rich nanoparticles are of wide ranging
importance in biomedicine. They include liposomes, bicelles, nanodiscs, exosomes
and virus particles. The quantitative study of these particles requires methods
for high-resolution visualization of the whole population. One powerful imaging
method is cryo-EM of vitrified samples, but this is technically demanding,
requires specialized equipment, provides low contrast and does not reveal all
particles present in a population. Another approach is classical negative stain
EM, which is more accessible but is difficult to standardize for larger lipidic
structures, which are prone to artifacts of structure collapse and contrast
variability. A third method uses embedment in methylcellulose films containing
uranyl acetate as a contrasting agent. Methylcellulose embedment has been widely
used for contrasting and supporting cryosections but only sporadically for
visualizing lipid rich vesicular structures such as endosomes and exosomes. Here
we present a simple methylcellulose-based method for routine and comprehensive
visualization of synthetic lipid rich nanoparticles preparations, such as
liposomes, bicelles and nanodiscs. It combines a novel double-staining mixture of
uranyl acetate (UA) and tungsten-based electron stains (namely phosphotungstic
acid (PTA) or sodium silicotungstate (STA)) with methylcellulose embedment. While
the methylcellulose supports the delicate lipid structures during drying, the
addition of PTA or STA to UA provides significant enhancement in lipid structure
display and contrast as compared to UA alone. This double staining method should
aid routine structural evaluation and quantification of lipid rich nanoparticles
structures.
PMID- 28419917
TI - The effect of social exclusion on state paranoia and explicit and implicit self
esteem in a non-clinical sample.
AB - BACKGROUND AND OBJECTIVES: The relationship between self-esteem and paranoia may
be influenced by social stress. This study aimed to replicate previous research
on the impact ofsocial exclusion on paranoia and self-esteem in a non-clinical
sample and to extend this work by examining the effect of exclusion on self
esteem at the 'implicit' level. METHODS: Non-clinical participants (N = 85) were
randomly allocated to the Inclusion or Exclusion condition of a virtual ball-toss
game ('Cyberball'). They completed self-reportmeasures of state paranoia and self
esteem, and two implicit measures of self-esteem - theImplicit Association Task
(IAT) and Implicit Relational Assessment Procedure (IRAP) -prior to and after
exposure to Cyberball. RESULTS: Social exclusion increased state paranoia. This
effect was moderated by distress associated with trait paranoia. Exclusion was
also associated with decreased self-reported self-esteem, as well as reduced
implicit self-esteem on the IAT. Changes in self-reported self-esteem were
associated with state paranoia at post-Cyberball. The IRAP indicated that
reductions in implicit self-esteem may be due to increases in 'Me-Negative' and
'Others-Positive' biases (rather than reductions in 'Me-Positive' bias).
LIMITATIONS: The current study involved a non-clinical sample and so findings
cannot be generalized to clinical paranoia. CONCLUSIONS: These findings are
consistent with previous evidence that paranoia is associated with negative self
evaluations, whereas positive self-evaluations can persist in paranoia. They also
provide support for the suggestion that investigations of self-esteem in paranoia
should extend beyond global self-esteem and might benefit from a distinction
between positive and negative components.
PMID- 28419918
TI - Internal shifting impairments in response to emotional information in dysphoric
adolescents.
AB - BACKGROUND AND OBJECTIVES: Previous studies have suggested that internal
cognitive control impairments may play an important role in the development of
depression. Despite a growing body of research in adults, the ability to shift
internal attention between mental representations in working memory has received
little attention in younger populations. This study investigated internal
shifting capacity between emotional and non-emotional information in dysphoric
and non-dysphoric adolescents. METHODS: Twenty dysphoric and 34 non-dysphoric
adolescents (10-17 years) completed an Internal Shifting Task, with pictures of
angry and neutral faces, to measure the ability to shift attention between
information held in working memory. RESULTS: Dysphoric adolescents showed
specific shifting impairments when processing emotional material relative to non
dysphoric adolescents. Valence-specific analyses revealed that shifting was
particularly impaired when shifting from negative to neutral information. By
comparison, relative to non-dysphoric adolescents, dysphoric adolescents did not
show shifting impairments when non-emotional features of the pictures had to be
processed. LIMITATIONS: The study is limited by the absence of a structured
clinical interview as dysphoria was determined dimensionally. Furthermore, a
comparison of the effects of different negative stimuli on shifting could not be
made since sad stimuli were not included in the stimulus set. CONCLUSIONS: The
results confirm the link between depressive symptoms and emotion-specific
shifting impairments in adolescents and indicate that targeting shifting ability
in response to emotional stimuli may be a promising avenue for prevention
programs. Longitudinal research is needed to replicate results and to explore the
role of internal shifting impairments in the etiology and maintenance of
depression.
PMID- 28419919
TI - Synthesis of layered titanate nanowires at low temperature and their application
in efficient removal of U(VI).
AB - Uranium(VI) has become one of the most potential contaminants due to its
productive and irreversibility impact on the surrounding environment. Titanate
nanowires (TNWs) have attracted significant attention because of its high ion
exchange ability and facile synthesis. Herein the TNWs were synthesized, and the
morphology and structure of TNWs were investigated by Fourier transformed
infrared spectroscopy, scanning electron microscope, transmission electron
microscope, X-ray diffraction and X-ray photoelectron spectroscopy in detail. The
application of TNWs in U(VI) removal was studied under various environmental
conditions using batch technique, and the results indicated that the sorption of
U(VI) on TNWs was strongly affected by pH and weakly affected by ionic strength.
The presence of PO43- and CO32- could overwhelmingly influence U(VI) interaction
with TNWs, which was mainly attributed to the formation of anionic and electro
neutral complexes. From the Langmuir model simulation, the maximum sorption
capacities were calculated to be 358, 384, and 410 mg g-1 at the temperatures of
298 K, 313 K and 328 K, respectively. The thermodynamic results revealed that the
interaction process was spontaneous and endothermic. The extraordinary ion
exchange capacity and facile synthesis under mild conditions made TNWs promising
materials for the potential application in the efficient elimination of U(VI) or
other lanthanides and actinides from aqueous solutions in the environmental
radioactive pollution cleanup.
PMID- 28419920
TI - The retention and distribution of parent, alkylated, and N/O/S-containing
polycyclic aromatic hydrocarbons on the epidermal tissue of mangrove seedlings.
AB - The polycyclic aromatic hydrocarbons (PAHs) located on the epidermal tissues
showed distinctive toxic effects to root, while the retention and distribution of
PAHs on mangrove seedlings poorly understood. Our results confirmed that the
partition coefficients (Kf) of the PAHs retained on the epidermal tissue of
mangrove roots, such as Kandelia obovata, Avicennia marina and Aegiceras
corniculatum, were much higher than the Poaceae plants roots, for example wheat
and maize (Wild et al., 2005). Moreover, to the parent and alkyl PAHs, a well
negative correlation was observed between the surface polarity of these three
species of mangrove root and the Kf values (p < 0.05). To the N/O/S containing
PAHs, these relationships were not obviously due to existing of the pi-pi, n-pi
interactions and hydrogen bonding between the N/O/S-containing PAHs and epidermal
tissues. The PAHs retained on these three species of mangrove root epidermal
tissues formed larger clusters than that of on Poaceae plants, such as wheat and
maize (Wild et al., 2005) due to the limitation of the suberization of the root
exodermis and endodermis. After exposure of 30 d, rhizo- and endophytic bacteria
degraded parts of the N/O/S-containing PAHs to medium-lifetime fluorescence
substances. To our knowledge, this is the first time to assess the retention of
PAHs on the epidermal tissue of mangrove root, which will improve our
understanding of the root uptake PAHs process.
PMID- 28419921
TI - Development of PM2.5 and NO2 models in a LUR framework incorporating satellite
remote sensing and air quality model data in Pearl River Delta region, China.
AB - High resolution pollution maps are critical to understand the exposure and health
effect of local residents to air pollution. Currently, none of the single
technologies used to measure or estimate concentrations of pollutants can provide
sufficient resolved exposure data. Land use regression (LUR) models were
developed to combine ground-based measurements, satellite remote sensing (SRS)
and air quality model (AQM), together with geographic and local source related
spatial inputs, to generate high resolution pollution maps for both PM2.5 and NO2
in Pearl River Delta (PRD), China. Four sets of LUR models (LUR without SRS or
AQM, with SRS only, with AQM only, and with both SRS and AQM), all including
local traffic emissions and land use variables, were compared to evaluate the
contribution of SRS and AQM data to the performance of LUR models in PRD region.
For NO2, the annual model with SRS estimate performed best, explaining 60.5% of
the spatial variation. For PM2.5, the annual model with traditional predictor
variables without SRS or AQM estimates showed the best performance, explaining
88.4% of the spatial variation. Pollution surfaces at 200 m*200 m resolution were
generated according to the best performed models.
PMID- 28419922
TI - Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary
cultured rat proximal tubular cells.
AB - Calcium, as a ubiquitous second messenger, governs a large array of cellular
processes and is necessary for cell survival. More recently, it was observed that
the cytosolic Ca2+ concentration ([Ca2+]c) elevation could induce apoptosis in
primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but
the concrete mechanism is still unclear. This study was designed to investigate
the signal pathway involved in [Ca2+]c elevation-mediated apoptosis. The results
confirmed the elevation of [Ca2+]c by confocal microscopy and enhancement of the
apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were
exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels
of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic
Ca2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid
acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active
calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT
cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4
iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N
Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly
attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd.
As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the
apoptosis induced by Cd. Taken together, it could be concluded that [Ca2+]c
elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT
cells, triggered calpain-1 and caspase-3 activation in turn, and induced
apoptosis of rPT cells.
PMID- 28419923
TI - Development and applications of two colorimetric and fluorescent indicators for
Hg2+ detection.
AB - Two rhodamine-active probes RBAI (Rhodamine B-di-Aminobenzene-phenyl
Isothiocyanate) and RGAI (Rhodamine 6G-di-Aminobenzene-phenyl Isothiocyanate)
were designed, synthesized and characterized. The probes were developed as
fluorescent and colorimetric chemodosimeters in ethanol-water solution with a
broad pH span (5-10) and high selectivity toward Hg2+ but no significant response
toward other common competitive cations. The Hg2+-promoted ring opening of
spirolactam of the rhodamine moiety induced cyclic guanylation of the thiourea
moiety, which resulted in the dual chromo- and fluorogenic observation (off-on).
Cytotoxicity and bioimaging studies by L929 living cells and living mice
indicated that the probes were negligible cytotoxicity, cell permeable and
suitable for detecting Hg2+ in biological environments. Moreover, the new probes
not only displayed excellent abilities for the successful detection of Hg2+ in
L929 living cells and living mice but also able to detect Hg2+ by adsorbing on
solid surfaces and quantitative detection of Hg2+ in real water samples with good
recovery (more than 90%), indicating that they have promising prospect for
application for Hg2+ sensing in environmental and biological sciences.
PMID- 28419924
TI - Centrifugal partition chromatography in the isolation of minor ecdysteroids from
Cyanotis arachnoidea.
AB - Phytoecdysteroids are known for their various beneficial bioactivities in mammals
including a non-hormonal anabolic and adaptogenic effect. Cyanotis arachnoidea
extracts are extensively utilized worldwide as ecdysteroid-rich materials for
various purposes, e.g. food supplementation, use in agriculture and aquaculture,
etc. Preparative chromatography of ecdysteroids requires extensive use of methods
of different selectivity, and only a very limited number of papers are available
on related application of modern liquid-liquid chromatographic techniques. In
this work, a centrifugal partition chromatography (CPC) method was developed for
the isolation of two minor ecdysteroids, dacryhainansterone and calonysterone,
from a pre-purified commercial extract of Cyanotis arachnoidea. The biphasic
solvent system was optimized by HPLC, and was composed of n-hexane - ethyl
acetate - methanol - water (1:5:1:5, v/v/v/v). The isolated dacryhainansterone
and calonysterone represented 99.1% and 99.7% purity, respectively. Calonysterone
exerts a stronger effect on the protein kinase B (Akt) phosphorylation in
mammalian skeletal muscle cells than the abundant 20-hydroxyecdysone, while no
related data are available on dacryhainansterone. Despite their presence in food
supplements, neither compound has appropriately been assessed for safety and
efficacy. The reported method allows the gram scale isolation of these compounds,
opening ways to their in-depth pharmacological investigation.
PMID- 28419925
TI - Characterization and application of restricted access carbon nanotubes in online
extraction of anticonvulsant drugs from plasma samples followed by liquid
chromatography analysis.
AB - Anticonvulsant drugs are often used in the treatment of epilepsy. However, their
therapeutic monitoring is often necessary in order to obtain an appropriate dose
adjustment, due to the proximity between their therapeutic and toxic ranges. The
aim of this study was to carry out the synthesis, characterization and use of
restricted access carbon nanotubes (RACNTs) in an online method for the analyses
of phenobarbital and carbamazepine and primidone from untreated human blood
plasma by column switching liquid chromatography. Therefore, the synthesis of
RACNTs was carried out through coating commercial Carbon nanotubes with bovine
serum albumin (BSA) to subsequently use them as adsorbents in a column switching
system operating in the backflush mode. This material was evaluated through the
construction of the kinetic and isotherm curves. The experimental data for the
interaction of primidone with RACNTs were adequately adjusted to the
chemisorption and Sips models for the kinetic and adsorption studies,
respectively. The analytical curves ranged from 2.0 to 40.0mgL-1, with
correlation coefficients higher than 0.99, for all the analytes. The LODs of 0.1,
0.1 and 0.01MUgmL-1 were defined for PHB, PRM and CBZ, respectively. The relative
standard deviation values ranged from 1.0% to 8.4% for the intra assay precision
and from 2.7% to 7.6% for inter assay precision. The relative error values ranged
from -13.4% to 7.7% for the intra assay accuracy and from -8.6% to 2.5% for the
inter assay accuracy. The method was adequately used in the therapeutic
monitoring of anticonvulsant drugs in human plasma samples.
PMID- 28419926
TI - Stability and activity of immobilized trypsin on carboxymethyl chitosan
functionalized magnetic nanoparticles cross-linked with carbodiimide and
glutaraldehyde.
AB - Enzyme cross-linkers, such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
(EDC) and glutaraldehyde (GA), have been used to improve the stability of
immobilized enzymes. We have developed a relatively stable and high-activity
immobilized trypsin through EDC and GA cross-linking. Carboxymethyl chitosan (CM
CTS)-functionalized magnetic nanoparticles (Fe3O4@CM-CTS) were prepared, and
characterized by Fourier transform infrared spectroscopy (FTIR),
thermogravimetric analysis, X-ray diffraction, and transmission electron
microscopy. The CM-CTS loading of Fe3O4 @CM-CTS was 8.701%, and the CM-CTS
coating did not cause any significant changes in the crystal structure of Fe3O4.
The Fe3O4@CM-CTS nanoparticles exhibited superparamagnetic properties. Trypsin
was successfully immobilized on Fe3O4@CM-CTS via EDC and GA cross-linking
(Fe3O4@CM-CTS-EDC-TRY and Fe3O4@CM-CTS-GA-TRY, respectively). Trypsin
immobilization was verified by FTIR and enzyme assays. Changes in the secondary
structures of the immobilized trypsin were present in both Fe3O4@CM-CTS-EDC-TRY
and Fe3O4@CM-CTS-GA-TRY. However, kinetic studies demonstrated that the
immobilized trypsin retained efficient biocatalytic activity. Fe3O4@CM-CTS-EDC
TRY and Fe3O4@CM-CTS-GA-TRY both showed maximum catalytic activity at pH 8.4 and
45 degrees C, and retained 71% and 88.5%, respectively, of their initial
activities after 6 usage cycles, and 80% and 88% of their initial activities
after being stored for 14 d at 4 degrees C. The Fe3O4@CM-CTS-GA-TRY showed higher
activity and conformational stability than Fe3O4@CM-CTS-EDC-TRY, which indicates
that GA is effective for the immobilization of trypsin on Fe3O4@CM-CTS.
PMID- 28419927
TI - Synthesis and evaluation of anti-plasmodial and cytotoxic activities of
epoxyazadiradione derivatives.
AB - Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti
plasmodial activity against CQ-resistant and CQ-sensitive strains of the most
virulent human malaria parasite P. falciparum. A series of analogues were
synthesized by modification of the key structural moieties of this high yield
natural product. Out of the library of all compounds tested, compounds 3c and 3g
have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 +/-
0.29 MUM and 1.5 +/- 0.01 MUM) and CQ-resistant strains (IC50 1.3 +/- 1.08 MUM
and 1.2 +/- 0.14), while compounds 3k, 3l and 3m showed modest activity against
CQ-sensitive strain of P. falciparum with IC50 values of 2.3 +/- 0.4 MUM, 2.9 +/-
0.1 MUM and 1.7 +/- 0.06 MUM, respectively. Additionally, cytotoxic properties of
these derivatives against SIHA, PANC 1, MDA-MB-231, and IMR-3 cancer cell lines
were also studied and the results indicated that low cytotoxic potentials of all
the derivatives which indicating the high selectivity index of the compounds.
PMID- 28419928
TI - Design, synthesis and biological evaluation of 3-substituted-2-oxindole hybrid
derivatives as novel anticancer agents.
AB - The 2-oxindole nucleus is the central core to develop new anticancer agents and
its substitution at the 3-position can effect antitumor activity. Utilizing a
pharmacophore hybridization approach, a novel series of antiproliferative agents
was obtained by the modification of the structure of 3-substituted-2-oxindole
pharmacophore by the attachment of the alpha-bromoacryloyl moiety, acting as a
Michael acceptor, at the 5-position of 2-oxindole framework. The impact of the
substituent at the 3-position of 2-oxindole core on the potency and selectivity
against a panel of seven different cancer cell lines was examined. We found that
these hybrid molecules displayed potent antiproliferative activity against a
panel of four cancer cell lines, with one-to double digit nanomolar 50%
inhibitory concentrations (IC50). A distinctive selective antiproliferative
activity was obtained towards CCRF-CEM and RS4; 11 leukemic cell lines. In order
to study the possible mechanism of action, we observed that the two most active
compounds namely 3(E) and 6(Z) strongly induce apoptosis that follow the
mitochondrial pathway. Interestingly a decrease of intracellular reduced
glutathione content (GSH) and reactive oxygen species (ROS) production was
detected in treated cells compared with controls suggesting that these effects
may be involved in their mechanism of action.
PMID- 28419929
TI - (R)- and (S)-18F-labeled 2-arylbenzofurans with improved pharmacokinetics as beta
amyloid imaging probes.
AB - A new class of optical isomers of 2-arylbenzofuran derivatives were synthesized
and evaluated as potential beta-amyloid plaques imaging agents. Both
lipophilicity and signal-to-noise ratio were significantly improved by adding a
chiral hydroxyl group to 1-fluoro-3-(oxidanyl)propan-2-ol side chain. These
derivatives displayed moderate to high binding affinity towards Abeta1-42
aggregates. Four tracers possessing potent binding affinity (Ki < 30 nM) were
chosen for further investigation. In in vitro autoradiography studies, the four
selected probes showed effective binding to Abeta plaques in Tg mouse and AD
human brain tissue after labeled by 18F. The purified enantiomers displayed
apparent discrepancy in biodistribution experiments in normal mice, for (S)
enantiomers provided rather faster clearance than (R)-enantiomers. All in all,
(S)-[18F]17 (Ki = 14.6 nM) with excellent pharmacokinetics (brain2 min = 8.60%
ID/g, brain2 min/brain60 min = 14.1) deserves further evaluation.
PMID- 28419930
TI - Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid
derivatives as DNMT and HDAC inhibitors.
AB - DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) are important
epigenetic targets during anticancer drug development. Recent study indicates
that DNMT inhibitors and HDAC inhibitors display synergistic effects in certain
cancers, therefore, development of molecules targeting both DNMT and HDAC is of
therapeutic advantage against these cancers. Based on the structure of DNMT
inhibitor NSC-319745 and the pharmacophore characteristics of HDAC inhibitors, a
series of hydroxamic acid derivatives of NSC-319745 were designed and synthesized
as DNMT and HDAC multifunctional inhibitors. Most compounds displayed potential
DNMT inhibitory potency and potent HDAC inhibitory activity, especially compound
15a showed much better DNMT1 inhibitory potency than NSC-319745, and inhibited
HDAC1, HDAC6 with IC50 values of 57, 17 nM, respectively. Furthermore, the
synthesized compounds exhibited significant cytotoxicity against human cancer
cells K562 and U937. Further mechanistic studies demonstrated that 15a treatment
in U937 increased histones H3K9 and H4K8 acetylation, prompted P16 CpG islands
demethylation and upregulated P16 expression, regulated apoptosis-related protein
expression on the cellular level and induced remarkable U937 apoptosis. Moreover,
genotoxicity of representative compounds was evaluated. In summary, our study
provided a practical drug design strategy targeting multiple enzymes, and 15a
represents a novel and promising lead compound for the development of novel
epigenetic inhibitors as antitumor agents.
PMID- 28419931
TI - Applying the design-build-test paradigm in microbiome engineering.
AB - The recently discovered roles of human microbiome in health and diseases have
inspired research efforts across many disciplines to engineer microbiome for
health benefits. In this review, we highlight recent progress in human microbiome
research and how modifications to the microbiome could result in implications to
human health. Furthermore, we discuss the application of a 'design-build-test'
framework to expedite microbiome engineering efforts by reviewing current
literature on three key aspects: design principles to engineer the human
microbiome, methods to engineer microbiome with desired functions, and analytical
techniques to examine complex microbiome samples.
PMID- 28419932
TI - Competitive removal of heavy metal ions from squid oil under isothermal condition
by CR11 chelate ion exchanger.
AB - Heavy metal ions (HMIs) are serious threats to the environment. Sub-critical
water treatment was used to mimic contamination of squid oil in aqueous, metal
soap and oil phases. Isothermal adsorption of HMIs (Cu2+, Pb2+, Cd2+ and Zn2+)
was studied from aqueous phase to oil phase (493, 523, 548, and 573K) for
solutions with different initial concentration of HMIs was studied. Decomposition
of glycerides into fatty acids was favored at high subcritical temperatures, with
metal-soap phase showing the highest chelation ability toward Cu2+ (96%, isotherm
573K). The removal-ability of HMIs from contaminated oil was performed by CR11
chelate ion exchanger, showing facilitated removal from metal-soap and oil phases
at low temperatures compared to general-purpose PEI-chitosan bead and PEI
chitosan fiber sorbents. The chelation behavior of Pb2+ and Cd2+ was the same in
the OIL, with maximum values of 5.7*10-3 (mol/l) and 5.0*10-3 (mol/l) at 573K,
respectively. By contrast, concentration of Zn2+ ion showed a slight increase
with increasing temperature due to electrostatic forces between Zn2+ and active
sites of glycerides in oil phase. For oil solution, the selectivity of adsorption
for CR11, especially for Zn2+, was at least five-fold larger compared to PEI
chitosan bead and PEI-chitosan fiber adsorbents.
PMID- 28419933
TI - Planar polarized contractile actomyosin networks in dynamic tissue morphogenesis.
AB - The complex shapes of animal bodies are constructed through a sequence of simple
physical interactions of constituent cells. Mechanical forces generated by
cellular activities, such as division, death, shape change and rearrangement,
drive tissue morphogenesis. By confining assembly or disassembly of actomyosin
networks within the three-dimensional space of the cell, cells can localize
forces to induce tissue deformation. Tissue-scale morphogenesis emerges from a
collective behavior of cells that coordinates the force generation in space and
time. Thus, the molecular mechanisms that govern the temporal and spatial
regulation of forces in individual cells are elemental to organogenesis, and the
tissue-scale coordination of forces generated by individual cells is key to
determining the final shape of organs.
PMID- 28419934
TI - Genome research elucidating environmental adaptation: Dark-fly project as a case
study.
AB - Organisms have the capacity to adapt to diverse environments, and environmental
adaptation is a substantial driving force of evolution. Recent progress of genome
science has addressed the genetic mechanisms underlying environmental adaptation.
Whole genome sequencing has identified adaptive genes selected under particular
environments. Genome editing technology enables us to directly test the role(s)
of a gene in environmental adaptation. Genome science has also shed light on a
unique organism, Dark-fly, which has been reared long-term in the dark. We
determined the whole genome sequence of Dark-fly and reenacted environmental
selections of the Dark-fly genome to identify the genes related to dark
adaptation. Here I will give an overview of current progress in genome science
and summarize our study using Dark-fly, as a case study for environmental
adaptation.
PMID- 28419935
TI - Identification of a host cell protein impurity in therapeutic protein, P1.
AB - Residual host cell proteins (HCPs) are process-related impurities present in
biotherapeutics that can pose safety health risks to patients. An adequate
control of HCP levels in the final product, and demonstration of HCP clearance
throughout a product manufacturing process is critical for all biotherapeutic
products. Developing effective downstream purification processes can be
challenging as HCPs and product proteins may possess an affinity for each other
or have similar physicochemical properties, resulting in co-purification. In the
current study, we identified the presence of CHO-catalase subunit protein as an
impurity present in purified P1 protein. This previously unreported HCP impurity,
was detected in P1 protein generated in Chinese hamster ovary (CHO) cells.
Purified drug substance samples contained elevated CHO HCP levels when measured
using a commercial anti-CHO HCP Enzyme-Linked Immunosorbent Assay (ELISA) kit.
This finding, prompted further characterization of the HCP profile using 1D and
2D gels/ western blots using an anti-human IgG antibody as well as a commercial
anti-CHO HCP antibody (Cygnus 813) for the detection of host cell proteins. The
CHO-catalase protein has been characterized using a combination approach of one
dimensional (1D) and two-dimensional (2D) gels and western blotting techniques,
and the identity confirmed using liquid chromatography-mass spectrometry (LC
MS/MS) analysis. Western blot analyses using the anti-CHO HCP antibody detected a
potential HCP band at ~60 kDa and a pI of ~8 in the purified P1 sample. The 60
kDa HCP band was excised from 1D SDS-PAGE gels and LC-MS/MS analysis identified
it to be CHO-catalase subunit. The identity of catalase monomer was further
confirmed by western blot analysis using a specific anti-catalase antibody.
PMID- 28419936
TI - Simultaneous separation and determination of four uncaria alkaloids by capillary
electrophoresis using dual cyclodextrin system.
AB - The purpose of this study was to develop a simple, quick and precise capillary
zone electrophoresis method (CZE) for the separation and determination of uncaria
alkaloids using dual cyclodextrins as additives for the separation. The four
analytes were baseline separated within 15min at the applied voltage of 15kV with
a running buffer (pH 5.7) consisting of 40.0mM phosphate buffer, 161.7mM 2
hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and 2.21mM mono-(6-ethylenediamine-6
deoxy)-beta-cyclodextrin (ED-beta-CD). Under the optimum conditions, a good
linearity was achieved with correlation coefficients from 0.9989 to 0.9992. The
detection limits and the quantitation limits ranged from 0.63 to 0.98MUg/mL and
from 2.08 to 3.28MUg/mL, respectively. Excellent accuracy and precision were
obtained. Recoveries of the analytes varied from 97.1 to 103.2%. This method was
suitable for the quantitative determination of these alkaloids in the stem with
hook of Uncaria rhynchophylla and the formulations of Uncaria rhynchophylla.
PMID- 28419937
TI - Validation and application of an ultrahigh-performance liquid chromatographic
Orbitrap mass spectrometric method for the simultaneous detection and
quantification of volatile and non-volatile organic acids in human faecal
samples.
AB - A simple and selective ultrahigh-performance liquid chromatographic-Orbitrap mass
spectrometric (UHPLC-HR-MS) method was developed and validated for the
simultaneous detection and quantification of short-chain fatty acids (SCFAs) such
as acetic, propionic, butyric, isobutyric, valeric, isovaleric, 2-methyl-butyric
(IS) and lactic, pyruvic and succinic acid in human faecal samples. A simple
extraction procedure with 0.001% formic acid in water was performed on 40
samples. The extracts were centrifuged and analyzed by UHPLC-HR-MS on a sub-2MUm
column using gradient elution; meanwhile, the same samples were analyzed by GC
FID and HPLC-UV as reference methods The UHPLC-HR-MS method showed a recovery of
83-105%, a repeatability of 2.2-8.3% and an intermediate precision of 2.9-9.4%.
The LOD and LLOQ were in the range of 0.04-0.23 and 0.2-0.5MUg/ml, respectively.
Regarding the SCFAs, statistical analysis showed a good correlation between the
data obtained by UHPLC-HR-MS and those provided by GC-FID (p>0.05). On the
contrary, the LC-UV data were not in agreement with those obtained by UHPLC-HR-MS
determination (p<0.05). To the best of our knowledge, this is the first method
available for the simultaneous extraction and quantification of SCFAs, lactic,
pyruvic and succinic in faecal samples by UHPLC-HR-MS.
PMID- 28419939
TI - The 5-HT4 receptor agonist prucalopride does not facilitate cholinergic
neurotransmission in circular and longitudinal smooth muscle preparations of
equine mid-jejunum.
AB - BACKGROUND: Postoperative ileus (POI) remains an important cause of death in
horses. The recently developed selective 5-HT4 receptor agonists such as
prucalopride target 5-HT4 receptors on myenteric cholinergic neurons to enhance
acetylcholine release and GI motility. No clearcut in vitro evaluation whether
highly selective 5-HT4 receptor agonists enhance submaximal cholinergic
neurotransmission towards the muscle layer has been performed in horses.
OBJECTIVES: To identify functional 5-HT4 receptors in equine jejunum. STUDY
DESIGN: In vitro experimental study. METHODS: Circular and longitudinal smooth
muscle strips (mid-jejunum) were mounted in organ baths between 2 platinum
electrodes allowing electrical field stimulation (EFS). To delineate the
conditions to obtain purely cholinergic responses, voltage-response curves were
studied. To investigate the influence of prucalopride and 5-HT, submaximal
cholinergic contractions at a single voltage were induced. RESULTS: In circular
and longitudinal strips, EFS induced voltage-dependent neurogenic on-contractions
when the bathing medium contained a NO-synthesis inhibitor and apamin to prevent
inhibitory responses to NO and ATP. Contractions at a voltage inducing 50% of
maximal amplitude were cholinergic, as they were blocked by atropine. These
contractions were not influenced by prucalopride (up to 3MUM), even in the
presence of the phosphodiesterase inhibitor isobutyl-methyl-xanthine to inhibit
breakdown of the second messenger of 5-HT4 receptors, cAMP. Also the full 5-HT4
receptor agonist 5-HT did not influence the EFS-induced submaximal cholinergic
contractions. Moreover, prucalopride did not influence muscle tone continuously
enhanced with KCl. CONCLUSIONS: There are no functional 5-HT4 receptors on
myenteric cholinergic neurons nor muscular 5-HT4 receptors in equine jejunum.
PMID- 28419938
TI - Direct-acting antivirals: the endgame for hepatitis C?
AB - Directly-acting antivirals (DAA) have finally allowed all patients to be
potentially cured from chronic hepatitis C (HCV) infection. All-oral, Interferon
(IFN)-free regimens are based upon the combination of molecules targeting
different sites of the HCV replication process. Three classes of DAA exist:
protease inhibitors (anti-NS3/4A), RNA-dependent polymerase inhibitors (anti
NS5B) and anti-NS5A inhibitors, which are characterized by different antiviral
potency and barrier to resistance and therefore are usually combined in different
treatment schedules. Treatment regimens are still largely dependent on HCV
genotype and stage of liver disease, with duration ranging between 12 weeks and
24 weeks, while overall treatment efficacy has climbed to nearly 95% in most
patient groups, including historically difficult-to-treat categories (HCV
genotype 1, advanced liver disease). The elimination of IFN has allowed safe and
efficacious treatment of patients formerly contraindicated to antiviral therapy,
such as decompensated cirrhosis and solid organ transplant recipients.
Availability of potent and safe antiviral drugs combined with improvement of
worldwide access to treatment could finally lead to HCV elimination in the next
decades.
PMID- 28419940
TI - Cholesterol concentrations in lipoprotein fractions separated by anion-exchange
high-performance liquid chromatography in healthy dogs and dogs with
hypercholesterolemia.
AB - Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for
measurement of cholesterol can be used to separate serum lipoproteins (high
density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density
lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX
HPLC has not been applied in veterinary practice. We had three objectives: (i)
the validation of AEX-HPLC methods including the correlation of serum cholesterol
concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation
HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was
investigated; (ii) the reference intervals of lipoprotein fractions measured by
AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions
from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23)
were compared. Analytic reproducibility and precision of AEX-HPLC were
acceptable. Positive correlation between serum concentrations of total
cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL
Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for
AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia.
Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol,
HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16
3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant
difference in lipoprotein profiles between healthy and dogs with
hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate
lipoprotein profiles in dogs and could be a new useful indicator of
hyperlipidemia in dogs.
PMID- 28419941
TI - PAMAM (generation 4) incorporated gelatin 3D matrix as an improved dermal
substitute for skin tissue engineering.
AB - The study explored the prospects of PAMAM (generation 4) applicability in gelatin
based scaffolds for skin tissue engineering. The effect of PAMAM on physico
chemical and biological characteristics of gelatin scaffolds was evaluated.
Gelatin scaffolds (with/without PAMAM) were prepared by lyophilization,
chemically crosslinked by glutaraldehyde and characterized for their morphology
(pore size), chemical features (bond nature), water adsorption, biodegradation
and biological compatibility. The study demonstrated that addition of PAMAM did
not significantly alter the pore size distribution or porosity of the scaffolds.
However, water adsorption potential and collagenase mediated degradation
significantly enhanced over period of the study. Both the scaffolds (with/without
PAMAM) were highly biocompatible and hemocompatible. PAMAM (G4) blended scaffolds
showed relatively higher cellular adhesion and proliferation of both
keratinocytes and fibroblasts with an improved gene expression profile of native
collagen type I of fibroblasts. Moreover, expression of angiogenesis inducing
genes, HIF1alpha and VEGF were also higher in PAMAM blended gelatin matrix. Also,
PAMAM incorporated gelatin matrix showed a slower rate of drug release which
confirms its suitability for therapeutic delivery during wound healing. These
results clearly suggest that blending PAMAM (G4) into the matrix could provide an
additional support to scaffold assisted wound healing.
PMID- 28419942
TI - Nucleotide-directed syntheses of gold nanohybrid systems with structure-dependent
optical features: Selective fluorescence sensing of Fe3+ ions.
AB - This study demonstrates a one-step synthesis for the preparation of both
adenosine monophosphate (AMP)-stabilized colloidal gold nanoparticles (AMP-Au
NPs) and fluorescent gold nanoclusters (AMP-Au NCs). The dominant role of
AMP:AuCl4- molar ratios in the formation of diverse nanosized Au products was
proved. The size, the structure and the unique structure-dependent optical
properties of the NPs and NCs were determined based on the results of numerous
spectroscopic (UV-vis, fluorescence, infrared, x-ray photoelectron), high
resolution electron microscopy (HRTEM) and dynamic light scattering (DLS)
techniques. Stabile AMP-Au NPs with diameter of ca. 11nm and ultra-small AMP-Au
NCs having blue fluorescence (lambdaem=480nm) were identified. In addition, the
AMP-Au NCs have been utilized to develop a selective sensor for the detection of
Fe3+ ions in aqueous medium based on fluorescence quenching. Several essential
metal ions and anions have been tested but our results clearly supported that
dominant quenching was observed only for Fe3+ ions. Based on the determined limit
of detection (LOD=2.0MUM) our system is capable of detecting Fe3+ ions in
drinking water. The Stern-Volmer constants (KSV) and various thermodynamic
parameters (DeltaG, DeltaH degrees , DeltaS degrees , DeltaCp) of the quenching
process have also been determined by the Stern-Volmer fitting of the fluorescence
data in order to better understand the quenching mechanism.
PMID- 28419943
TI - Interconnectivity of macroporous molecularly imprinted polymers fabricated by
hydroxyapatite-stabilized Pickering high internal phase emulsions-hydrogels for
the selective recognition of protein.
AB - Hydroxyapatite hybridized molecularly imprinted polydopamine polymers with
selective recognition of bovine hemoglobin (BHb) were successfully prepared via
Pickering oil-in-water high internal phase emulsions-hydrogels and molecularly
imprinting technique. The emulsions were stabilized by hydroxyapatite of which
the wettability was modified by 3-methacryloxypropyltrimethoxysilane. The
materials were characterized by SEM, IR and TGA. The results showed that the BHb
imprinted polymers based on Pickering hydrogels (Hydro-MIPs) possess macropores
ranging from 20MUm to 50MUm, and their large numbers of amino groups and hydroxyl
groups result in a favorable adsorption capacity for BHb. The maximum adsorption
capacity of Hydro-MIPs for BHb was 438mg/g, 3.27 times more than that of the non
imprinted polymers (Hydro-NIPs). The results indicated that Hydro-MIPs possessing
well-defined hierarchical porous structures exhibited outstanding recognition
behavior towards the target protein molecules. This work provided a promising
alternative method for the fabrication of polymer materials with tunable and
interconnected pores structures for the separation and purification of protein in
vitro.
PMID- 28419944
TI - Electrochemical synthesis of three-dimensional porous reduced graphene oxide
film: Preparation and in vitro osteogenic activity evaluation.
AB - In this study, three-dimensional reduced graphene oxide (3D-rGO) porous films
were fabricated using a two-step electrochemical method, including an
electrochemical deposition process for the self-assembly of GO and an
electrochemical bubbling-based transfer. The morphology, physical properties, and
phase composition of the 3D-rGO films were characterized, and the cellular
bioactivities were evaluated using pre-osteoblasts (MC3T3-E1 cells). The
attachment, proliferation and differentiation of the MC3T3-E1 cells on the 3D-rGO
films was analyzed by scanning electron microscopy (SEM), Cell Counting Kit-8
(CCK-8) assays and live/dead cell staining, and alkaline phosphatase (ALP)
activity assays, respectively. The expression of osteogenic-related genes in
MC3T3-E1 cells was evaluated by reverse transcription-polymerase chain reaction
(RT-PCR). The results showed that the 3D-rGO films supported cell viability and
proliferation, as well as significantly enhanced ALP activity and osteogenic
related genes (ALP, OPN, Runx2) expressions. Our findings indicate the promising
potential of the 3D-rGO porous films for bone tissue engineering.
PMID- 28419945
TI - Interaction of alpha-synuclein with Rhus typhina tannin - Implication for
Parkinson's disease.
AB - The etiology of Parkinson's disease (PD) relates to alpha-synuclein, a small
protein with the ability to aggregate and form Lewy bodies. One of its prevention
strategies is inhibition of alpha-synuclein oligomerization. We have investigated
the interaction of alpha-synuclein and human serum albumin with 3,6-bis-O-di-O
galloyl-1,2,4-tri-O-galloyl-beta-d-glucose (a tannin isolated from the plant Rhus
typhina). Using fluorescence spectroscopy method we found that this tannin
interacts strongly with alpha-synuclein forming complexes. Circular dichroism
analysis showed a time-dependent inhibition of alpha-synuclein aggregation in the
presence of the tannin. On the other hand, 3,6-bis-O-di-O-galloyl-1,2,4-tri-O
galloyl-beta-d-glucose had a much stronger interaction with human serum albumin
than alpha-synuclein. The calculated binding constant for tannin-protein
interaction was considerably higher for albumin than alpha-synuclein. This tannin
interacted with albumin through a "sphere of action" mechanism. The results lead
to the conclusion that 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-beta-d-glucose
is a potent preventive compound against Parkinson's disease. However, this tannin
interacts very strongly with human serum albumin, significantly reducing the
bioavailability of this compound.
PMID- 28419946
TI - Water-immiscible bioinert coatings and film formation from aqueous dispersions of
poly(2-methoxyethyl acrylate) microspheres.
AB - Poly(2-methoxyethyl acrylate) (pMEA) microspheres are prepared through facile
free-radical polymerization in water without additives and impurities, such as
surfactants, other polymers, and organic solvents, which are usually used to
synthesize pMEA chains. Clean and pure (non-factionalized and non-cross-linking)
pMEA microspheres exhibit plasma-protein adsorption resistances on their surface
regardless of their charged state. They are characterized in terms of the
adsorbed amounts of proteins at pH 7. In addition, these soft and deformable pMEA
microspheres are suitable for forming substrates coated with pMEA microspheres
and free-standing films by injecting pMEA dispersion and evaporating the aqueous
medium through fusion between the pMEA chains at the surface without the
precoating agent and cross-linker. These pMEA coatings have been used till now in
artificial heart/lung fabrication and metal products manufacturing by casting
organic solvents such as 1,4-dioxane, toluene, and methanol and dissolving pMEA
chains prepared using conventional solution polymerization. In this study,
bioinert coatings and adhesive and transferable films are easily obtained due to
the rubber-like properties of the pMEA microspheres and stable in mild and
biocompatible conditions even when these impurities are not used completely,
allowing us to provide a guideline for potential pMEA bioapplications such as
coatings, films, barriers, and implant devices.
PMID- 28419947
TI - Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal
epilepsy: Case series.
AB - PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug
licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety
of ESL have been established in real-life setting. However, data about outcomes
in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL
in elderly patients. METHOD: This was a retrospective survey that included
patients >65years with focal seizures who started ESL between January 2010 and
July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to
real-life practice. Efficacy and safety were evaluated over 1year. These patients
were included within the bigger study ESLIBASE. RESULTS: We included 29 patients,
most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20
years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose
was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were
seizure-free. At 12 months, 16 patients (55.2%) had >=1 adverse effect (AE), that
led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most
common AEs. The tolerability profile improved in 4/5 patients who switched from
carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL
was well-tolerated and effective in elderly patients in a real-life setting over
1year, with a dose around 800mg/day. AE effects improved in most of who switched
from CBZ or OXC to ESL.
PMID- 28419948
TI - Genetic generalized epilepsy in three siblings with 8q21.13-q22.2 duplication.
AB - PURPOSE: Duplication of chromosome region 8q21-q22 is a rare copy number variant
that has been previously reported in a limited number of patients. Although some
of these patients had seizures, their electroclinical syndrome has not been
described in detail. The aim of this study was to provide further insight into
the specific epilepsy syndrome associated with 8q21.13-q22.2 duplication. METHOD:
We describe 3 siblings with trisomy of 8q21.13-q22.2 who exhibited intellectual
disability, facial dysmorphism and seizures. RESULTS: All of the patients
responded satisfactorily to antiepileptic medication. The EEG showed typical 3-Hz
generalized spike-and-wave interictal discharges. Microarray analyses revealed
duplication of 8q21.13-q22.2, encompassing 10 OMIM morbid map genes. The analysis
demonstrated that the parental origin of the additional copy of 8q22.13-q22.2 was
maternal, translocated to chromosome 4p. CONCLUSION: Our report supports that
duplication of 8q21.13-q22.2 is associated with genetic generalized epilepsy with
early onset absence and generalized tonic clonic seizures, in addition to the
previously reported features of intellectual disability and dysmorphism.
PMID- 28419949
TI - Characteristics of seizure-induced signal changes on MRI in patients with first
seizures.
AB - PURPOSE: The aim of this study was to investigate the predictive factors and
identify the characteristics of the seizure-induced signal changes on MRI (SCM)
in patients with first seizures. METHODS: We conducted a retrospective study of
patients with first seizures from March 2010 to August 2014. The inclusion
criteria for this study were patients with 1) first seizures, and 2) MRI and EEG
performed within 24h of the first seizures. The definition of SCM was hyper
intensities in the brain not applying to cerebral arterial territories.
Multivariate logistic regression was performed with or without SCM as a dependent
variable. RESULTS: Of 431 patients with seizures visiting the ER, 69 patients met
the inclusion criteria. Of 69 patients, 11 patients (15.9%) had SCM. Epileptiform
discharge on EEG (OR 29.7, 95% CI 1.79-493.37, p=0.018) was an independently
significant variable predicting the presence of SCM in patients with first
seizures. In addition, the topography of SCM was as follows; i) ipsilateral
hippocampus, thalamus and cerebral cortex (5/11), ii) unilateral cortex (4/11),
iii) ipsilateral thalamus and cerebral cortex (1/11), iv) bilateral hippocampus
(1/11). Moreover, 6 out of 7 patients who underwent both perfusion CT and MRI
exhibited unilateral cortical hyperperfusion with ipsilateral thalamic
involvement reflecting unrestricted vascular territories. CONCLUSION: There is an
association between epileptiform discharges and SCM. Additionally, the
involvement of the unilateral cortex and ipsilateral thalamus in SCM and its
hyperperfusion state could be helpful in differentiating the consequences of
epileptic seizures from other pathologies.
PMID- 28419950
TI - River bottom sediment from the Vistula as matrix of candidate for a new reference
material.
AB - Bottom sediments are very important in aquatic ecosystems. The sediments
accumulate heavy metals and compounds belonging to the group of persistent
organic pollutants. The accelerated solvent extraction (ASE) was used for
extraction of 16 compounds from PAH group from bottom sediment of Vistula. For
the matrix of candidate of a new reference material, moisture content, particle
size, loss on ignition, pH, and total organic carbon were determined. A gas
chromatograph with a selective mass detector (GC/MS) was used for the final
analysis. The obtained recoveries were from 86% (SD=6.9) for anthracene to 119%
(SD=5.4) for dibenzo(ah)anthracene. For the candidate for a new reference
material, homogeneity and analytes content were determined using a validated
method. The results are a very important part of the development and
certification of a new reference materials.
PMID- 28419951
TI - Can fractal methods applied to video tracking detect the effects of deltamethrin
pesticide or mercury on the locomotion behavior of shrimps?
AB - Shrimps can accumulate environmental toxicants and suffer behavioral changes.
However, methods to quantitatively detect changes in the behavior of these
shrimps are still needed. The present study aims to verify whether mathematical
and fractal methods applied to video tracking can adequately describe changes in
the locomotion behavior of shrimps exposed to low concentrations of toxic
chemicals, such as 0.15ugL-1 deltamethrin pesticide or 10ugL-1 mercuric chloride.
Results showed no change after 1min, 4, 24, and 48h of treatment. However, after
72 and 96h of treatment, both the linear methods describing the track length,
mean speed, mean distance from the current to the previous track point, as well
as the non-linear methods of fractal dimension (box counting or information
entropy) and multifractal analysis were able to detect changes in the locomotion
behavior of shrimps exposed to deltamethrin. Analysis of angular parameters of
the track points vectors and lacunarity were not sensitive to those changes. None
of the methods showed adverse effects to mercury exposure. These mathematical and
fractal methods applicable to software represent low cost useful tools in the
toxicological analyses of shrimps for quality of food, water and biomonitoring of
ecosystems.
PMID- 28419952
TI - Antimony and arsenic exhibit contrasting spatial distributions in the sediment
and vegetation of a contaminated wetland.
AB - Antimony is a priority environmental contaminant that is relatively poorly
studied compared to other trace metal(loid)s. In particular, the behaviour of
antimony in wetland sediments, where anaerobic conditions often dominate, has
received considerably less attention compared to well-drained terrestrial soil
environments. Here we report the results of a spatial assessment of antimony in
the sediments and vegetation of a freshwater wetland exposed to stibnite tailings
for the past forty years. The concentration of antimony in the sediment decreased
rapidly with distance from the tailings deposit, from a maximum of ~22,000 mg kg
1 to ~1000 mg kg-1 at a distance of ~150 m. In contrast, arsenic was distributed
more evenly across the wetland, indicating that it was more mobile under the
prevailing hypoxic/anoxic conditions. Less clear trends were observed in the
tissues of wetland plants, with the concentrations of antimony in waterlilies
(2.5-195 mg kg-1) showing no clear trends with distance from the tailings
deposit, and no correlation with sediment concentrations. Sedges and Melaleuca
sp. trees had lower antimony concentrations (<25 mg kg-1 and 5 mg kg-1,
respectively) compared to waterlilies, but showed a non-significant trend of
higher concentrations closer to the tailings. For all vegetation types sampled,
antimony concentrations were consistently lower than arsenic concentrations
(Sb:As = 0.27-0.31), despite higher concentrations of antimony in the sediment.
Overall, the results of this study highlight clear differences in the behaviour
of antimony and arsenic in freshwater wetlands, which should be considered during
the management and remediation of such sites.
PMID- 28419953
TI - Exploiting extracellular polymeric substances (EPS) controlling strategies for
performance enhancement of biological wastewater treatments: An overview.
AB - Extracellular polymeric substances (EPS) are present both outside of the cells
and in the interior of microbial aggregates, and account for a main component in
microbial aggregates. EPS can influence the properties and functions of microbial
aggregates in biological wastewater treatment systems, and specifically EPS are
involved in biofilm formation and stability, sludge behaviors as well as
sequencing batch reactors (SBRs) granulation whereas they are also responsible
for membrane fouling in membrane bioreactors (MBRs). EPS exhibit dual roles in
biological wastewater treatments, and hence the control of available EPS can be
expected to lead to changes in microbial aggregate properties, thereby improving
system performance. In this review, current updated knowledge with regard to EPS
basics including their formation mechanisms, important properties, key component
functions as well as sub-fraction differentiation is given. EPS roles in
biological wastewater treatments are also briefly summarized. Special emphasis is
laid on EPS controlling strategies which would have the great potential in
promoting microbial aggregates performance and in alleviating membrane fouling,
including limitation strategies (inhibition of quorum sensing (QS) systems,
regulation of environmental conditions, enzymatic degradation of key components,
energy uncoupling etc.) and elevation strategies (enhancement of QS systems,
addition of exogenous agents etc.). Those strategies have been confirmed to be
feasible and promising to enhance system performance, and they would be a
research niche that deserves further study.
PMID- 28419954
TI - Osmoregulatory responses to cadmium in reference and historically metal
contaminated Gammarus fossarum (Crustacea, Amphipoda) populations.
AB - In order to better understand the variable sensitivities of crustaceans to
metals, we investigated the impact of cadmium exposure in 3 populations of
Gammarus fossarum from different rivers of France. The first population lives in
a Cd-contaminated river from a geochemical background, while the others inhabit
Cd-free sites. Osmoregulation, a relevant biomarker to evaluate crustacean health
following metal contamination, was used as a proxy to evaluate the intra- and
inter-populationnal sensitivities to Cd. Specimens from each population were
experimentally exposed to 9 MUg Cd2+/L Cd for 7 days and hemolymph osmolality
(HO) was then individually measured. In exposed populations, high inter
individual variations in HO values were noted, resulting in their separation into
non-impacted and slightly or highly Cd-impacted (with lower HO) animals. In gills
of impacted organisms, deep histopathological alterations and protein
overexpression of Na+/K+-ATPase and V-H+-ATPase were observed through histology
and immunolocalization, while non-impacted animals showed profiles comparable to
controls. Moreover, the osmoregulatory processes in the population living in the
Cd-contaminated site were impacted by acute Cd exposure in the laboratory as much
as for one of the two populations originating from Cd-free sites. The observed
changes did not reveal any obvious adaptive osmoregulatory phenomena at the
population scale, but they may be due to differences in fitness between
individuals and between populations in relation to the features of their
respective environments, unrelated with the presence of the metal.
PMID- 28419955
TI - Photodegradation of 4,4'-dibrominated diphenyl ether in Triton X-100 micellar
solution.
AB - This study has investigated the photochemical reactions of 4,4'-dibrominated
diphenyl ether (BDE-15) in Triton X-100 (TX-100) solution by UV light. All
photolysis experiments were performed in TX-100 solutions which were all above
critical micelle concentration (CMC). BDE-15 photodegradation follows the pseudo
first-order kinetics under various conditions. The results showed that the
degradation rates of BDE-15 increased with the increasing concentration of TX
100, and decreased when TX-100 was used in excess, because TX-100 can act as
hydrogen donor, photosensitizer and light barrier. When the pH value was in the
range of 1-11, the degradation rates increased with the increasing pH value due
to the proton effect and free radical reaction. When pH reached 13, the
corresponding degradation rate dropped significantly, which was attributed to the
decreasing surface potential of micellar retarding the degradation process. BDE
15 was debrominated into 4-dibrominated diphenyl ether (BDE-3) and diphenyl ether
(DE), subsequently. In addition, dibenzofuran (DF), ortho-hydroxydiphenyl and
para-hydroxydiphenyl were identified as another group of photoproducts,
indicating PBDEs can also undergo the photochemical rearrangement via CO bond
cleavage and recombination of the radical fragments.
PMID- 28419956
TI - Towards improved behavioural testing in aquatic toxicology: Acclimation and
observation times are important factors when designing behavioural tests with
fish.
AB - The quality and reproducibility of science has recently come under scrutiny, with
criticisms spanning disciplines. In aquatic toxicology, behavioural tests are
currently an area of controversy since inconsistent findings have been
highlighted and attributed to poor quality science. The problem likely relates to
limitations to our understanding of basic behavioural patterns, which can
influence our ability to design statistically robust experiments yielding
ecologically relevant data. The present study takes a first step towards
understanding baseline behaviours in fish, including how basic choices in
experimental design might influence behavioural outcomes and interpretations in
aquatic toxicology. Specifically, we explored how fish acclimate to behavioural
arenas and how different lengths of observation time impact estimates of basic
swimming parameters (i.e., average, maximum and angular velocity). We performed a
semi-quantitative literature review to place our findings in the context of the
published literature describing behavioural tests with fish. Our results
demonstrate that fish fundamentally change their swimming behaviour over time,
and that acclimation and observational timeframes may therefore have implications
for influencing both the ecological relevance and statistical robustness of
behavioural toxicity tests. Our review identified 165 studies describing
behavioural responses in fish exposed to various stressors, and revealed that the
majority of publications documenting fish behavioural responses report extremely
brief acclimation times and observational durations, which helps explain
inconsistencies identified across studies. We recommend that researchers applying
behavioural tests with fish, and other species, apply a similar framework to
better understand baseline behaviours and the implications of design choices for
influencing study outcomes.
PMID- 28419957
TI - Arsenic in groundwater of the Kolkata Municipal Corporation (KMC), India:
Critical review and modes of mitigation.
AB - This study represents the first comprehensive report of groundwater arsenic
contamination status in the Kolkata Municipal Corporation (KMC). During the past
23 years, 4210 groundwater samples were analysed from all 141 wards in the KMC:
14.2% and 5.2% samples had arsenic >10 MUg/l and >50 MUg/l, respectively,
representing 77 and 37 wards. The study shows that the number of arsenic
contaminated samples (and wards) in the southern part of the KMC exceeds that of
other parts of the city. The daily intake of arsenic from drinking water was
estimated as 0.95 MUg per kg bw and the cancer risk was estimated as 1425/106.
Analyses of biological samples (hair, nail and urine) showed elevated
concentrations of arsenic indicating the presence of subclinical arsenic
poisoning, predicting an enhanced lifetime cancer risk for the population in
southern part of the KMC. In the KMC, groundwater is not a sustainable source of
freshwater due to arsenic, high iron, hardness and total dissolved solids. Its
continued use is impelled by the lack of an adequate infrastructure to treat and
supply surface water and in some wards the unaccounted for water (UFW) is even
>45% incurred during distribution. The rare imposition of a water tax makes the
water supply systems unsustainable and fosters indifference to water
conservation. To mitigate the arsenic problem, continuous groundwater monitoring
for pollutants, a treated surface water supply with strict policy implications,
rainwater harvesting in the urban areas and introduction of water taxes seem to
be long-term visible solutions.
PMID- 28419958
TI - Arsenate and fluoride enhanced each other's uptake in As-sensitive plant Pteris
ensiformis.
AB - We investigated the effects of arsenate (AsV) and fluoride (F) on each other's
uptake in an As-sensitive plant Pteris ensiformis. Plants were exposed to 1) 0.1
* Hoagland solution control, 2) 3.75 mg L-1 As and 1.9, 3.8, or 7.6 mg L-1 F, or
3) 1 mg L-1 F and 3.75 mg L-1 or 7.5 mg L-1 As for 7 d in hydroponics. P.
ensiformis accumulated 14.7-32.6 mg kg-1 As at 3.75 mg L-1 AsV, and 99-145 mg kg
1 F at 1 mg L-1 F. Our study revealed that AsV and F increased each other's
uptake when co-present. At 1.9 mg L-1, F increased frond As uptake from 14.7 to
40.3 mg kg-1, while 7.5 mg L-1 As increased frond F uptake from 99 to 371 mg kg
1. Although, AsV was the predominant As species in all tissues, F enhanced AsIII
levels in the rhizomes and fronds, while the reverse was observed in the roots.
Increasing As concentrations also enhanced TBARS and H2O2 in tissues, indicating
oxidative stress. However, F alleviated As stress by lowering their levels in the
fronds. Frond and root membrane leakage were also evident due to As or F
exposure. The results may facilitate better understanding of the mechanisms
underlying the co-uptake of As and F in plants. However, the mechanisms of how
they enhance each other's uptake in P. ensiformis need further investigation.
PMID- 28419959
TI - Substance abuse in patients with bipolar disorder: A systematic review and meta
analysis.
AB - By considering the debilitating outcome of co-occurring of bipolar disorder (BD)
and substance abuse, determination of risk factors of substance use disorders
(SUD: abuse or dependence of drugs and/or alcohol) is essential to identify the
susceptible patients. The purpose of this study was to clarify the major
determinant factors of SUD among adults with BD by reviewing the relevant
literature. We systematically searched electronic databases including PubMed
(MEDLINE), EMBASE, OVID, Cochrane and Scopus for human studies addressing the co
existence of bipolar disorder and SUD. All potential published papers up to
September 2016 have been reviewed. The statistical analysis was performed using
Comprehensive Meta-analysis version 2. Male gender (Odds ratio: 2.191 (95% CI:
1.121-4.281), P 0.022), number of manic episodes (P: 0.001) and previous history
of suicidality (Odds ratio: 1.758 (95% CI: 1.156-2.674), P: 0.008) were
associated to SUD in patients with BD. SUD was not related to age, subtype of BD,
hospitalization and co-existence of anxiety disorders or psychotic symptoms. SUD
affects many aspects of BD regarding clinical course, psychopathology and
prognosis. Our study demonstrates that male gender, history of higher number of
manic episodes and suicidality are associated to higher susceptibility to SUD.
Thus, assignment of more intensive therapeutic interventions should be considered
in patients with increased risk of drug abuse to prevent development of SUD.
PMID- 28419960
TI - Preferentially enhancing anti-cancer isothiocyanates over glucosinolates in
broccoli sprouts: How NaCl and salicylic acid affect their formation.
AB - Broccoli (Brassica oleracea L. var. italica) sprouts contain glucosinolates (GLs)
that when hydrolysed yield health promoting isothiocyanates such as sulforaphane
(SF). SF content can be increased by salt (NaCl) stress, although high salt
concentrations negatively impact plant growth. Salicylic acid (SA) treatments can
attenuate the negative effects of salt on growth. To test whether sprout
isothiocyanate content could be elevated without sprout growth being compromised,
broccoli seed were germinated and grown for seven days in salt (0, 80 and 160 mM)
alone and in combination with 100 MUM SA. Increasing concentrations of salt
lowered transcript accumulation of GL biosynthetic genes which was reflected in
lowered content of Gluconapin, 4-methoxyglucobrassicin and neoglucobrassicin
glucosinolates. Other glucosinolates such as glucoraphanin did not alter
significantly. Salt (160 mM) increased transcript abundance of the GL hydrolytic
gene MYROSINASE (BoMYO) and its cofactor EPITHIOSPECIFIER MODIFIER1 (BoESM1)
whose encoded product directs MYROSINASE to produce isothiocyanate rather than
nitrile forms. SF content was increased 6-fold by the 160 mM salt treatment, but
the salt treatment reduced percentage seed germination, slowed seed germination,
and reduced sprout hypocotyl elongation. This growth inhibition was prevented if
100 MUM SA was included with the salt treatment. These findings suggest that the
increase in SF production by salt occurs in part because of increased transcript
abundance of genes in the hydrolytic pathway, which occurs independently of the
negative impact of salt on sprout growth.
PMID- 28419961
TI - Evidence towards the involvement of nitric oxide in drought tolerance of
sugarcane.
AB - Exogenous supply of nitric oxide (NO) increases drought tolerance in sugarcane
plants. However, little is known about the role of NO produced by plants under
water deficit. The aim of this study was to test the hypothesis that drought
tolerance in sugarcane is associated with NO production and metabolism, with the
more drought-tolerant genotype presenting higher NO accumulation in plant
tissues. The sugarcane genotypes IACSP95-5000 (drought-tolerant) and IACSP97-7065
(drought-sensitive) were submitted to water deficit by adding polyethylene glycol
(PEG-8000) in nutrient solution to reduce the osmotic potential to -0.4 MPa. To
evaluate short-time responses to water deficit, leaf and root samples were taken
after 24 h under water deficit. The drought-tolerant genotype presented higher
root extracellular NO content, which was accompanied by higher root nitrate
reductase (NR) activity as compared to the drought-sensitive genotype under water
deficit. In addition, the drought-tolerant genotype had higher leaf intracellular
NO content than the drought-sensitive one. IACSP95-5000 exhibited decreases in
root S-nitrosoglutathione reductase (GSNOR) activity under water deficit,
suggesting that S-nitrosoglutathione (GSNO) is less degraded and that the drought
tolerant genotype has a higher natural reservoir of NO than the drought-sensitive
one. Those differences in intracellular and extracellular NO contents and
enzymatic activities were associated with higher leaf hydration in the drought
tolerant genotype as compared to the sensitive one under water deficit.
PMID- 28419962
TI - Temporal trends of PBDEs and emerging flame retardants in belugas from the St.
Lawrence Estuary (Canada) and comparisons with minke whales and Canadian Arctic
belugas.
AB - An exponential level increase of the ubiquitous halogenated flame retardant (HFR)
class polybrominated diphenyl ether (PBDE) has been documented during the 1990s
in endangered belugas (Delphinapterus leucas) from the St. Lawrence Estuary
(SLE), Eastern Canada. The recent worldwide bans and regulations of PBDE mixtures
led to their replacement by alternative HFRs (so-called emerging HFRs) that are
increasingly being reported in various environmental compartments. There are,
however, limited knowledge on the spatial and temporal trends of PBDEs and
emerging HFRs in cetaceans, especially after restrictions on PBDE usage. The
first objective of this study was to investigate the occurrence of HFRs (35 PBDE
congeners and 13 emerging compounds) in the blubber of belugas and minke whales
(Balaenoptera acutorostrata) found dead in the Estuary or Gulf of St. Lawrence as
well as belugas from Nunavik (Canadian Arctic) collected as part of the Inuit
subsistence hunt. A second objective was to investigate the trends of HFR
concentrations in SLE beluga males between 1997 and 2013. PBDEs were the most
abundant HFRs in all three whale populations, while hexabromobenzene (HBB),
Chlordene Plus (CPlus), Dechlorane Plus (DP), and Dechlorane 604 Component B (Dec
604 CB) were quantified in the majority of blubber samples. Overall,
concentrations of emerging HFRs were notably greater in SLE belugas compared to
the two other whale populations, with the exception of DP and Dec-604 CB that
were found in greater concentrations in Canadian Arctic belugas. No significant
trend in blubber PBDE concentrations was found in SLE belugas during this 17-year
period. This suggests that global PBDE regulations are too recent to observe
changes in PBDE concentrations in belugas from this highly HFR-exposed
environment. In contrast, concentrations of HBB and CPlus in SLE belugas
decreased slightly from 1997 to 2013, while DP increased up until 2000 and
decreased slightly thereafter. The occurrence and temporal variations of PBDEs
and their replacement products in these cetaceans warrant continuous monitoring.
PMID- 28419963
TI - Acute toxicity and anti-fatigue activity of polysaccharide-rich extract from corn
silk.
AB - The aim of this study was to evaluate the safety and potential of PCS as the anti
fatigue functional food. PCS was prepared by water extracting-alcohol
precipitating method, and its chemical compositions of monosaccharide were
analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated.
PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17:
0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were
observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body
weight and food consumption were not significantly changed compared with the
normal control group. The relative weights of main organ, and biochemical
indicators also did not markedly change. PCS can significantly prolong the
duration of the swimming time to exhaustion in mice, decrease BUN, LA levels,
increase LDH activities, and the contents of HG in the PCS treated mice. The dose
of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in
male and female mice. In conclusion, PCS is a promising traditional natural-based
therapeutic remedy for relieving fatigue with high safety.
PMID- 28419964
TI - Effects of Paeonia emodi on hepatic cytochrome P450 (CYP3A2 and CYP2C11)
expression and pharmacokinetics of carbamazepine in rats.
AB - Herbal medicines, dietary supplements, and other foods may pharmacokinetically
and/or pharmacodynamically interact with carbamazepine (CBZ), which could lead to
potential clinical consequences. Paeonia emodi (PE) is one of the herbs used as
complementary therapy in the treatment of epileptic patients in some cultures,
and may also be co-administered with CBZ. This study evaluates the effects of PE
on the pharmacokinetics of CBZ and determines a possible mechanism of
interaction. Rats were administered vehicle saline or PE (200mg/kg, p.o. daily
for 7days), then administered a single CBZ dose (80mg/kg, p.o.) on day 7. Plasma
samples were analyzed for CBZ concentrations using a sensitive reversed-phase
high-performance liquid chromatography (RP-HPLC) assay. Pharmacokinetic
parameters were calculated using non-compartmental analysis. The co
administration of PE with CBZ resulted in increased plasma maximum concentration
(Cmax), area under the curve (AUC0-infinity), and half-life (T1/2), by 14.61%,
48.12%, and 43.72%, respectively. The calculated oral clearance (CL/F) was
reduced by 33.54%, while the volume of distribution (Vss) was unaffected. The PE
extract also showed a significant potential to reduce CYP3A and CYP2C protein
expression by approximately 50%. Therefore, a reduction in the metabolic capacity
responsible for CBZ clearance appears to be the mechanism behind this herb-drug
interaction. Consequently, the concomitant administration of PE and CBZ should be
viewed cautiously. Further studies are needed to determine the clinical relevance
of these observations.
PMID- 28419965
TI - Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect
in combination with cytarabine.
AB - Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for
treatment of T-cell lymphomas in multiple clinical trials. It has been
demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce
differentiation in leukemia cells, whereas its effect on acute myeloid leukemia
(AML) patients with FLT3-ITD mutation has not been clarified. In this study, we
found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD
positive AML cells in a concentration and time-dependent manner. We also found
chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML
cells. Moreover, with respect to relapsed/refractory patients, chidamide showed
the same effectiveness as that in de novo AML patients. Notably, chidamide
synergistically enhanced apoptosis caused by cytarabine. Our results support
chidamide alone or combine with cytarabine may be used as an alternative
therapeutic choice for AML patients especially those with FLT3-ITD mutation or
relapsed/refractory ones.
PMID- 28419966
TI - Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in
hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway.
AB - Emerging evidence suggests that tumorigenesis involves dysregulation of small
nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11)
in the development of hepatocellular carcinoma (HCC) remains unknown. Expression
of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC
cell lines. We found that ACA11 expression was significantly upregulated in HCC
tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was
significantly associated with histological grade, HBV infection, Barcelona Clinic
Liver Cancer stage, portal vein tumor thrombus and poorer patient survival.
Knockdown of ACA11 induced G0/G1 phase arrest and suppressed proliferation,
migration and invasion of HCCLM9 and SK-Hep1 cells. Low ACA11 expression resulted
in decreased HCC growth in an animal model. Conversely, transgenic expression of
ACA11 induced S phase progression and enhanced proliferation, migration and
invasion of Huh7 cells in vitro and in vivo. Finally, we found that ACA11
promoted cell growth, migration and invasion through activation of the PI3K/AKT
pathway, subsequently increasing cyclinD1 expression and inducing EMT. These
results suggest that ACA11 has an oncogenic role in HCC and may serve as a
promising prognostic biomarker and therapeutic target for patients with HCC.
PMID- 28419967
TI - Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial
efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis
and invasion in vitro.
AB - Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive
(GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive
therapy. In the present study, the potential anti-angiogenic and anti-invasive
effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+)
tumours. OLE (2mg/mL) caused a significant reduction in tumour weight,
vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004;
respectively) that was associated with reducing the expression of VEGFA, MMP-2
and MMP-9. This effect was synergistically increased in combination with
bevacizumab. Therefore, our current findings may contribute to research on drugs
that inhibit the invasiveness of GBM.
PMID- 28419968
TI - Current insights into pathogenesis of Parkinson's disease: Approach to mevalonate
pathway and protective role of statins.
AB - Although Parkinson's disease (PD) is considered as the second most common life
threatening age-related neurodegenerative disorder, but the underlying mechanisms
for pathogenesis of PD are remained to be fully found. However, a complex
relationship between genetic and environmental predisposing factors are involved
in progression of PD. Dopaminergic neuronal cell death caused by mutations and
accumulation of alpha-synuclein in Lewy bodies and neurites was suggested as the
main strategy for PD, but current studies have paid attention to the role of
mevalonate pathway in incidence of neurodegenerative diseases including PD. The
discovery may change the therapeutic protocols from symptomatic treatment by
dopamine precursors and agonists to neurodegenerative process halting drugs.
Moreover, the downstream metabolites of mevalonate pathway may be used as
diagnostic biomarkers for early diagnosis of PD. Statins, as cholesterol lowering
drugs, may ameliorate the enzyme complex dysfunction, a key step in the
progression of the neurodegenerative disorders, oxidative stress-induced damage
and neuro-inflammation. Statins exert the neuroprotective effects on striatal
dopaminergic neurons through blocking the mevalonate pathway. In the present
review, we have focused on the new approaches to pathogenesis of PD regarding to
mevalonate pathway, in addition to the previous understood mechanisms for the
disease. It tries to elucidate the novel findings about PD for the development of
future diagnostic and therapeutic strategies. Moreover, we explain the
controversial role of statins in improvement or progression of PD and the
position of these drugs in neuroprotection in PD patients.
PMID- 28419969
TI - Neurotoxic effects of silver nanoparticles and the protective role of rutin.
AB - The toxicological studies on silver nanoparticles (Ag-NPs) have become a hot
topic over the past few decades due to their unique properties on the nanoscale
and widespread in many commercial products that launched into the market
recently. This study was undertaken to shed light on Ag-NPs toxicity on
neurotransmitters with special emphasis on the impact of concurrent
administration of rutin with Ag-NPs in the experimental rats. The oral
administration of Ag-NPs in rats induced brain oxidative stress, significant
alterations in neurotransmitters and amino acids. Furthermore, transcriptional
levels of glutamatergic N-methyl-d-aspartate (NMDA) receptors, monoamino oxidases
(MAO-A, MAO-B) and metallothionein-III (MT-III) showed a significant elevation in
Ag-NPs intoxicated rats. Moreover, histological examinations revealed
astrogliosis and demyelination of neurons concomitant with neuronal degeneration
and vacuolation. Strikingly, oral administration of rutin counterbalanced the
toxic effects triggered by Ag-NPs. Taken together, our findings suggested that
oral administration of Ag-NPs induced neurotoxicity in rats and rutin mitigates
these effects.
PMID- 28419970
TI - Effect of premedication with subcutaneous adrenaline on the pharmacokinetics and
immunogenicity of equine whole IgG antivenom in a rabbit model.
AB - Subcutaneous administration of a low dose of adrenaline is used to prevent the
early adverse reactions (EARs) induced by snake antivenoms. We used a rabbit
model to study the effect of premedication with adrenaline on the potential of
antivenoms to exert therapeutic effects and to induce late adverse reactions. We
found that premedication with adrenaline did not change the heart rate or blood
pressure of normal rabbits, but reduced the rise in temperature in rabbits
previously sensitized with antivenom. Pharmacokinetic studies suggest that
premedication with adrenaline does not affect the ability of the antivenom to
exert the initial control of envenomation nor the susceptibility of rabbits to
develop recurrence of antigenemia and envenomation. Our results also indicate
that it is unlikely that premedication with adrenaline decreases the incidence of
late reactions induced by the antivenom administration, although it reduces the
extent of early reactions.
PMID- 28419971
TI - miR-493-5p suppresses hepatocellular carcinoma cell proliferation through
targeting GP73.
AB - Aberrant expression of miRNAs has been documented to play critical roles in the
development and progression of hepatocellular carcinoma (HCC). However, the
expression pattern, functional roles and regulatory mechanism of miR-493-5p in
HCC have not been addressed. Herein, we found that miR-493-5p was significantly
downregulated in HCC tissues and was tightly associated with tumor size, tumor
differentiation grade and TNM stage of HCC patients. Overexpression of miR-493-5p
inhibited HCC cell proliferation, arrested cell cycle in G0/G1 phase and induced
cell apoptosis. Bioinformatical analysis and luciferase reporter assay further
proved that Golgiprotein73 (GP73), an oncogene which was generally overexpressed
in HCC, acted as a novel target of miR-493-5p. MiR-493-5p could inhibit GP73 both
mRNA and protein expression. Moreover, overexpression of GP73 could reverse the
inhibitory effects of miR-493-5p mediated HCC cell proliferation. In addition,
upregulated GP73 in HCC tissues was inversely correlated with the miR-493-5p
expression levels in the HCC tissues. Collectively, our present study
demonstrates that miR-493-5p is downregulated in HCC and it can suppress the
proliferation of HCC cells, partly at least, via directly targeting GP73.
Besides, this study provides a novel insight into the mechanism of
hepatocarcinogenesis and a promising blueprint for miR-493-5p-GP73 axis-oriented
treatment of HCC.
PMID- 28419972
TI - Neprilysin inhibitors: A new hope to halt the diabetic cardiovascular and renal
complications?
AB - Diabetes is an enormous and ever-growing calamity and a global public health
threat of the 21st century. Besides insulin and oral hypoglycaemic drugs,
blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for
the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which
are the leading causes of disability and death among diabetic patients.
Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the
bioavailability of natriuretic peptides and benefits the cardio-renal system.
Omapatrilat, a dual angiotensin-converting enzyme (ACE) and NEP inhibitor has
been reported to show superior anti-hypertensive, anti-atherosclerotic, insulin
sensitizing, cardiovascular and renoprotective effects to ACE inhibitors in
experimental animal models for diabetes. In clinical trials on hypertensive
subjects Omapatrilat increased the risk of angioedema due to which its further
development as anti-hypertensive drug was hampered. This event prompted the
development of angiotensin receptor neprilysin inhibitors (ARNi). The first
representative of ARNi, LCZ696 (Sacubitril/ Valsartan) halted cardiovascular and
renal functional decline and hence protected against CKD and CVD. Recently,
LCZ696 was approved by U.S. Food and Drug Administration for the treatment of
heart failure. This concise review intends to summarise the currently available
reports on NEPi as a therapeutic intervention to treat CVD and CKD associated
with diabetes.
PMID- 28419973
TI - Antibacterial, antifungal and antimycobacterial compounds from cyanobacteria.
AB - Infections from multidrug resistant (MDR) pathogenic bacteria, fungi and
Mycobacterium tuberculosis remain progressively intractable. The search of
effective antimicrobials from other possible non-conventional sources against MDR
pathogenic bacteria, fungi and mycobacteria is call of the day. This review
considers 121 cyanobacterial compounds or cyano-compounds with antimicrobial
activities. Chemical structures of cyano-compounds were retrieved from ChemSpider
and PubChem databases and were visualized by the software ChemDraw Ultra.
Chemical information on cyano-compounds pertaining to Lipinski rules of five was
assessed. The reviewed cyano-compounds belong to the following chemical classes
(with examples): alkaloids (ambiguine isonitriles and 12-epi-hapalindole E
isonitrile), aromatic compounds (benzoic acid and cyanobacterin), cyclic
depsipeptides (cryptophycin 52 and lyngbyabellin A), cyclic peptides (calophycin
and tenuecyclamides), cyclic undecapeptides (kawaguchipeptins and lyngbyazothrin
A), cyclophane (carbamidocyclophane), extracellular pigment (nostocine A), fatty
acids (alpha-dimorphecolic acid and majusculonic acid), linear peptides
(muscoride A), lipopeptides (fischerellins and scytonemin A), nucleosides
(tolytoxin and tubercidin), phenols (ambigols and 4-4'-hydroxybiphenyl),
macrolides (scytophycin A and tolytoxin), polyketides (malyngolide and
nostocyclyne), polyphenyl ethers (crossbyanol A), porphinoids (tolyporphin J) and
terpenoids (noscomin and scytoscalarol). Cyanobacteria appear to be a diverse
source of compounds with antimicrobial activity. Further attention is required to
elucidate whether those could be applied as pharmaceuticals.
PMID- 28419974
TI - Prediction and feature analysis of intron retention events in plant genome.
AB - Alternative splicing (AS) is a major contributor to increase the potential
informational content of eukaryotic genomes by creating multiple mRNA species and
proteins from a single gene. In plants, up to 60% genes are alternatively spliced
and the most common type of AS is intron retention (IR). Genomic analyses of IR
have illuminated its crucial role in shaping the evolution of genomes, in the
control of developmental processes, and in the dynamic regulation of the
transcriptome to influence phenotype. To explore the relationship between the
sequence feature and the formation mechanism of IR, we statistically analyzed the
retained introns and proposed an improved random forest-based hybrid method to
predict intron retention events in plant genome. The results indicate that IR has
significant relationship with individual introns which have weaker 5' splice
sites, lower GC content and less termination codon occurrence. By the method we
proposed, 93.48% retained introns can be correctly distinguished from
constitutive introns. Strikingly, our study will facilitate a better
understanding of underlying mechanisms involved in intron retention.
PMID- 28419975
TI - Animal models for neuropsychiatric disorders: prospects for circuit intervention.
AB - Monogenic animal models for psychiatric diseases have enabled researchers to
dissect the relationship between certain candidate genes, neural circuit
abnormalities, and behavioral phenotypes along development. Early reports of
phenotypic reversal after genetic restoration in mouse models sparked hope that
genetic defects do not damage circuits irreversibly in early-onset disorders.
However, further studies have suggested that only some circuits exhibit this
plasticity, while many others require proper gene function during development.
This review focuses on what we have learned from a few evolutionarily conserved
circuit-phenotype relationships and their developmental windows to illustrate
their importance when considering intervention strategies.
PMID- 28419976
TI - Microbial extracellular enzymes in biogeochemical cycling of ecosystems.
AB - Extracellular enzymes, primarily produced by microorganisms, affect ecosystem
processes because of their essential roles in degradation, transformation and
mineralization of organic matter. Extracellular enzymes involved in the cycling
of carbon (C), nitrogen (N) and phosphorus (P) have been widely investigated in
many different ecosystems, and several enzymes have been recognized as key
components in regulating C storage and nutrient cycling. In this review, it was
the first time to summarize the specific extracellular enzymes related to C
storage and nutrient cycling for better understanding the important role of
microbial extracellular enzymes in biogeochemical cycling of ecosystems.
Subsequently, ecoenzymatic stoichiometry - the relative ratio of extracellular
enzyme, has been reviewed and further provided a new perspective for
understanding biogeochemical cycling of ecosystems. Finally, the new insights of
using microbial extracellular enzyme in indicating biogeochemical cycling and
then protecting ecosystems have been suggested.
PMID- 28419977
TI - Investigation of As(V) removal from acid mine drainage by iron (hydr) oxide
modified zeolite.
AB - In this work, the synthesis of iron (hydr) oxide modified zeolite was achieved
through precipitation of iron on the zeolite. The structure and surface
morphology of iron (hydr) oxide modified zeolite (IHOMZ) was studied by scanning
electron microscopy (SEM), coupled with an energy-dispersive X-ray spectroscopy
(EDX), and Fourier transform infrared (FT-IR) spectra. The efficiency of IHOMZ
was then investigated through batch technique for the extraction of As(V) from
mine waste water. The optimum parameters for maximum As(V) adsorption were: an
initial As(V) concentration (10 mg L-1), adsorbent dosage (3.0 g), contact time
(90 min) and temperature (53 degrees C). The initial pH of the solution had no
compelling effect on As(V) adsorption by IHOMZ. However, adsorption capacity was
significantly affected by the solution temperature with 53 degrees C registering
the maximum removal efficiency. The thermodynamic parameters: Entropy (DeltaS
degrees = 0.00815 kJ (K mol)-1), variation of the Gibbs free energy (DeltaG
degrees ) and enthalpy (DeltaH degrees = 9.392 kJ mol-1) of As(V) adsorption
onto IHOMZ system signified a non-spontaneous and endothermic process. It was
noted that Freundlich isotherm model exhibited a better fit to the equilibrium
experimental data, implying that the adsorption process occurred on a
heterogeneous surface. The kinetic data from As(V) adsorption experiments was
depicted by the pseudo-second-order kinetic model (R2 > 0.999), suggesting a
chemisorption adsorption process. The experimental batch equilibrium results
indicated that IHOMZ could be used as an effective sorbent for As(V) ion
extraction from acid mine drainage.
PMID- 28419978
TI - Dissolved oxygen, stream temperature, and fish habitat response to environmental
water purchases.
AB - Environmental water purchases are increasingly used for ecological protection. In
Nevada's Walker Basin (western USA), environmental water purchases augment
streamflow in the Walker River and increase lake elevation of terminal Walker
Lake. However, water quality impairments like elevated stream temperatures and
low dissolved oxygen concentrations also limit ecosystems and species, including
federally-threatened Lahontan cutthroat trout. In this paper, we prioritize water
volumes and locations that most enhance water quality for riverine habitat from
potential environmental water rights purchases. We monitored and modeled
streamflows, stream temperatures, and dissolved oxygen concentrations using River
Modeling System, an hourly, physically-based hydrodynamic and water quality
model. Modeled environmental water purchases ranged from average daily increases
of 0.11-1.41 cubic meters per second (m3/s) during 2014 and 2015, two critically
dry years. Results suggest that water purchases consistently cooled maximum daily
stream temperatures and warmed nightly minimum temperatures. This prevented
extremely low dissolved oxygen concentrations below 5.0 mg/L, but increased the
duration of moderate conditions between 5.5 and 6.0 mg/L. Small water purchases
less than approximately 0.71 m3/s per day had little benefit for Walker River
habitat. Dissolved oxygen concentrations were affected by upstream environmental
conditions, where suitable upstream water quality improved downstream conditions
and vice versa. Overall, this study showed that critically dry water years
degrade environmental water quality and habitat, but environmental water
purchases of at least 0.71 m3/s were promising for river restoration.
PMID- 28419979
TI - Clinical profile of persistent genito-pelvic postpartum pain.
AB - : OBJECTIVE*: the primary aim was to describe the pain characteristics of
persistent genito-pelvic postpartum pain (PPP) and compare these characteristics
by mode of delivery. The secondary aim was to incorporate psychosocial variables
into the conceptualization of PPP by exploring the relationship among postpartum
depressive symptoms, fatigue, and PPP. DESIGN: cross-sectional study design.
SETTING: online survey. PARTICIPANTS: 106 women recruited from the community who
gave birth within twelve months prior to completing the survey. MEASUREMENTS AND
FINDINGS: questionnaire regarding sociodemographic information, pregnancy and
childbirth variables, depressive symptoms (Edinburgh Postnatal Depression Scale),
and fatigue (Fatigue Symptom Checklist). Women who were >=3 months postpartum and
indicated they were still experiencing any genito-pelvic pain from childbirth
were provided questions about their current pain experience. Twenty-seven (25.5%)
women were between 3-12 months postpartum and currently experiencing PPP. The
intensity of pain was mild, and had multiple locations and triggers. Compared to
women whose acute pain resolved after childbirth, women with PPP were more likely
to have had a Caesarean section (15.2% versus 33.3%). Other birth-related (i.e.,
epidural/spinal anesthesia use during vaginal birth) and psychosocial variables
(income) also differentiated women with PPP from women whose gentio-pelvic pain
resolved. Postpartum fatigue independently predicted PPP (Odds ratio = 4.7),
while postpartum depressive symptoms did not. KEY CONCLUSIONS: PPP was quite
prevalent in this sample, and while the intensity of pain was on average, mild,
the pain was widespread in terms of location and triggers. Multiple
biopsychosocial factors differentiated women with persistent postpartum pain from
those women whose pain resolved. IMPLICATIONS FOR PRACTICE: PPP is a common
health concern for new mothers in the first year postpartum, and may be best
addressed by health care professionals using a multidimensional approach, which
focuses on the psychosocial aspects of pain.
PMID- 28419980
TI - Evaluation of GLUT1 variation in non-acquired focal epilepsy.
AB - Brain glucose transport is dependent on glucose transporter 1 (GLUT1), encoded by
the solute carrier family 2 member 1 (SLC2A1) gene. Mutations in SLC2A1 cause
GLUT1 deficiency which is characterized by a broad spectrum of neurological
phenotypes including generalized epilepsy, motor disorders, developmental delay
and microcephaly. Recent case reports suggest SLC2A1 mutations can contribute to
non-acquired focal epilepsy (NAFE) but interrogation of a large patient cohort
has not been reported. We studied 200 patients with NAFE (126 with temporal lobe
epilepsy) comprising 104 females and 96 males with a mean age of onset of 18
years. Polymerase chain reaction (PCR) and Sanger sequencing was performed to
detect variants in all 10 coding exons and splice site regions of the SLC2A1
gene. We did not detect any pathogenic mutations in SLC2A1 in this cohort. Our
data suggests that the frequency of GLUT1 mutations in NAFE is low. Limitations
of this study include the mean age of onset and cohort size. Future research
should focus on subpopulations of focal epilepsy with lower age of seizure onset
particularly with co-existent movement disorders in which GLUT1 mutations may
play a more important role.
PMID- 28419981
TI - Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An
Observational Multicenter International Study.
AB - BACKGROUND: Hyponatremia is a frequent and potentially life-threatening adverse
side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry
database focuses on current management practices of thiazide-associated
hyponatremia (TAH) and compares differences between TAH and syndrome of
inappropriate antidiuretic hormone secretion (SIADH). METHODS: We analyzed 477
patients from 225 US and EU sites with euvolemic hyponatremia ([Na+] <=130 mEq/L)
who were receiving a thiazide diuretic. Of these, 118 met criteria for true
thiazide-induced hyponatremia (TIH). RESULTS: Thiazide was withdrawn immediately
after hyponatremia was diagnosed only in 57% of TAH; in these patients, the
median rate of [Na+] change (Deltadaily[Na+]) was significantly higher than those
with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8]
mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%),
fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic
saline (5.2%). Hypertonic saline produced the greatest Deltadaily[Na+] (8.0[6.4]
mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5
[3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction
was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of
hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic
saline. Although there are highly significant differences in the biochemical
profiles between TIH and SIADH, no predictive diagnostic test could be derived.
CONCLUSIONS: Despite its high incidence and potential risks, the management of
TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment
success. Hypertonic saline is most effective in correcting hyponatremia but
associated with a high rate of overly rapid correction. We could not establish a
diagnostic laboratory-based test to differentiate TIH from SIADH.
PMID- 28419983
TI - Pam3CSK4 Induces MMP-9 Expression in Human Monocytic THP-1 Cells.
AB - BACKGROUND: Matrix metalloproteinase (MMP)-9 is known to degrade the
extracellular matrix and increased MMP-9 levels are related with the pathogenesis
of many inflammatory conditions including obesity. Pam3CSK4 is a synthetic
triacylated lipopeptide (LP) which is a potent activator of immune cells and
induces cytokine production. However, it is unclear whether Pam3CSK4 is able to
induce MMP-9 expression in monocytic cells. We, therefore, determined MMP-9
production by Pam3CSK4-treated THP-1 cells and also investigated the signal
transduction pathway(s) involved. METHODS: MMP-9 expression was determined by
real-time qPCR and ELISA. MMP-9 activity was assessed by zymography. THP-1 cells,
THP1-XBlueTM cells, THP1-XBlueTM-defMyD cells, anti-TLR2 mAb and selective
pharmacological inhibitors were used to study signaling pathways involved.
Phosphorylated and total proteins were detected by western blotting. RESULTS:
Pam3CSK4 induced MMP-9 expression (P<0.05) at both mRNA and protein levels in
human monocytic THP-1 cells. Increased NF-kappaB/AP-1 activity was detected in
Pam3CSK4-treated THP-1 cells and MMP-9 production in these cells was
significantly suppressed by pre-treatment with anti-TLR2 neutralizing antibody or
by inhibition of clathrin-dependent endocytosis. Also, MyD88-/- THP-1 cells did
not express MMP-9 following treatment with Pam3CSK4. Inhibition of JNK, MEK/ERK,
p38 MAPK and NF-kappaB significantly suppressed MMP-9 gene expression (P<0.05).
CONCLUSION: Pam3CSK4 induces MMP-9 production in THP-1 cells through the TLR
2/MyD88-dependent mechanism involving MEK/ERK, JNK, p38 MAPK and NF-kappaB/AP-1
activation.
PMID- 28419982
TI - Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure.
AB - BACKGROUND: Although high resting heart rate (RHR) is known to be associated with
an increased risk of mortality and hospital admission in patients with heart
failure, the relationship between RHR and ischemic stroke remains unclear. This
study is aimed at investigating the relationship between RHR and ischemic stroke
in patients with heart failure in sinus rhythm. METHODS: We examined 2,060
patients with systolic heart failure in sinus rhythm from the Warfarin versus
Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from
baseline electrocardiogram, and was examined as both a continuous variable and a
categorical variable using quartiles. Ischemic strokes were identified during
follow-up and adjudicated by physician review. RESULTS: During 3.5 +/- 1.8 years
of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an
ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was
observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups;
22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and
21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional
hazards analysis revealed that RHR was significantly associated with ischemic
stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR
<64/beats/min; p = 0.038), along with a history of stroke or transient ischemic
attack and left ventricular ejection fraction. CONCLUSIONS: In contrast to its
beneficial effect on mortality and hospital re-admissions, lower RHR may increase
the risk of ischemic stroke in patients with systolic heart failure in sinus
rhythm.
PMID- 28419984
TI - Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a
Receptor-Dependent Mechanism.
AB - BACKGROUND: Though vitiligo is a common depigmentary disorder, it still
represents a substantial therapeutic challenge. Therapeutic options are limited
in part due to its uncertain etiology. OBJECTIVE: Because recent studies suggest
that histamine stimulates melanogenesis in vitro, we determined here whether
topical histamine stimulates repigmentation in patients with stable, nonsegmental
vitiligo. METHODS: A total of 23 otherwise normal volunteers with vitiligo,
including 14 males and 9 females aged 6-59 years (mean age 29.2 +/- 2.8), were
enrolled in this study. 1% histamine in distilled water was applied to the
lesions twice daily for 5 weeks, while comparable lesions, treated with distilled
water alone, served as the controls. The melanin index was measured on the
uninvolved and lesional skin sites before and after 5 weeks of treatments using
the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne,
Germany). Changes in epidermal permeability barrier were also assessed at the
same time point. To determine whether histamine-induced repigmentation is
receptor-dependent, both ears of C57BL/6J mice were treated topically with 5%
cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10
days. One hour after each cimetidine application, the right ear was treated
topically with 10% histamine, while vehicle alone was applied to the left ear.
Changes in melanin index were measured 24 h after the last application of
histamine and vehicle as described in the human study. RESULTS: In patients with
vitiligo treated with vehicle alone for 5 weeks, the melanin index remained
unchanged, while topical histamine treatment increased the melanin index by 38%
(p < 0.001 vs. both vehicle and pretreatment), which was paralleled by a >60%
reduction in lesion surface area. Moreover, topical histamine accelerated
permeability barrier recovery. No adverse events were observed following
histamine applications. In mice, topical histamine significantly increased the
melanin index, while topical co-applications of the H2r antagonist (cimetidine)
prevented the expected histamine-induced increase in melanin index. CONCLUSIONS:
These studies indicate that topical histamine or an H2r agonist could be useful
for treating nonsegmental vitiligo, but further clinical studies in large
populations will be required to validate the efficacy and safety of this
approach.
PMID- 28419985
TI - Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat
Traumatic Brain Injury.
AB - BACKGROUND: Traumatic brain injury (TBI) can be complicated by TBI-triggered
acute lung injury (ALI), in which inflammation plays a central role. It has been
reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate
TBI; however, its function in TBI-caused ALI has not been reported yet. METHODS:
In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight
drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and
bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and
eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the
lungs were harvested for immunofluorescence staining and qRT-PCR analysis.
RESULTS: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased
wet/dry ratios, decreased total BALF protein, and attenuated the histological
signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the
accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF
alpha, IL-6, IL-1beta and iNOS in the lung. CONCLUSIONS: We identified the
protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a
potent candidate for systemic therapy in TBI patients.
PMID- 28419986
TI - Hypodysfibrinogenemia with a Heterozygous Mutation of gammaCys326Ser by the Novel
Transversion of TGT to TCT in a Patient with Pulmonary Thromboembolism and Right
Ventricular Thrombus.
AB - We encountered a 45-year-old Japanese man who suffered from pulmonary
thromboembolism and huge right ventricular thrombus after inferior vena cava
(IVC) filter implantation without apparent thrombus in either the deep veins or
inside the IVC filter. The biochemical data showed a discrepancy in the level of
fibrinogen between the immunological and thrombin time methods, suggesting
hypodysfibrinogenemia. The sequencing of the fibrinogen gamma-chain gene (FGG)
revealed a novel heterozygous missense mutation in exon 8 - a TGT to TCT
transversion in codon 326 - resulting in an amino acid substitution of serine for
cysteine (gammaCys326Ser). The characterization of the protein did not show known
mechanisms for thrombosis in dysfibrinogenemia, such as dimer or albumin-binding
complex formation. In summary, the current case with a life-threatening
thrombotic event was found to have a novel heterozygous missense mutation
resulting in gammaCys326Ser, which was suggested as a predisposing factor of the
thrombosis. Known mechanisms responsible for thrombosis in the current case were
not demonstrated, suggesting other mechanisms including superimposing inherited
and/or acquired risk factors. When a patient presents with unusual thrombosis
such as breakthrough pulmonary embolism and huge thrombus in the right ventricle,
as in the current case, the laboratory process for heritable thrombophilia should
be considered.
PMID- 28419987
TI - Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint
Osteoarthritis.
AB - Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that
affects both cartilage and subchondral bone. It is accompanied by loss of
extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2
(BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone
in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin
(Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type
(WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 ug/mL BMP-2 for 2
days using an explant culture system. Condyle growth was measured by microCT and
the expression levels of cartilage and bone-related genes were analyzed using RT
PCR or by immunohistochemistry from condyles that contained an intact
cartilage/subchondral bone interface. Osteoclast activity was estimated by
tartrate-resistant acid phosphatase (TRAP) staining and by TRAP, Rankl, and
Adamts4 mRNA expression levels. Our results showed that most parameters examined
were slightly up-regulated in WT samples treated with BMP-2, and this up
regulation was significantly enhanced in the Bgn-/-Fmod-/- mice. The up
regulation of both catabolic and anabolic agents did not appear to positively
affect the overall growth of Bgn-/-Fmod-/- condyles compared to WT controls. In
summary, the up-regulation of both anabolic and catabolic genes in the WT and Bgn
/-Fmod-/- TMJs treated with BMP-2 suggests that BMP increases matrix turnover in
the condyle, and, further, that Bgn and Fmod could have protective roles in
regulating this process.
PMID- 28419989
TI - Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute
Ischemic Stroke Patients.
AB - BACKGROUND: Low magnesium levels are associated with an elevated risk of stroke.
In this study, we investigated the association between magnesium levels on
hospital admission and in-hospital mortality in acute ischemic stroke (AIS)
patients. METHODS: A total of 2,485 AIS patients, enrolled from December 2013 to
May 2014 across 22 hospitals in Suzhou city, were included in this study. The
patients were divided into 4 groups according to their level of admission
magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and
Q4 (>=0.98 mmol/L). Cox proportional hazard model was used to estimate the effect
of magnesium on all-cause in-hospital mortality in AIS patients. RESULTS: During
hospitalization, 92 patients (3.7%) died from all causes. The lowest serum
magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in
hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56;
p-trend < 0.001). After adjusting for age, sex, time from onset to hospital
admission, baseline National Institutes of Health Stroke Scale score, and other
potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014).
Sensitivity and subgroup analyses further confirmed a significant association
between lower magnesium levels and a high risk of in-hospital mortality.
CONCLUSIONS: Decreased serum magnesium levels at admission were independently
associated with in-hospital mortality in AIS patients.
PMID- 28419988
TI - Neutrophil-to-Lymphocyte Ratio Is an Independent Predictor for In-Hospital
Mortality in Spontaneous Intracerebral Hemorrhage.
AB - BACKGROUND AND PURPOSE: Stroke-associated immunosuppression and inflammation are
increasingly recognized as factors that trigger infections and thus, potentially
influence the outcome after stroke. Several studies demonstrated that elevated
neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse
outcomes in patients with ischemic stroke. However, little is known about the
impact of NLR on short-term mortality in intracerebral hemorrhage (ICH). METHODS:
This observational study included 855 consecutive ICH-patients. Patient
demographics, clinical, laboratory, and in-hospital measures as well as
neuroradiological data were retrieved from institutional databases. Functional 3
months-outcome was assessed and categorized as favorable (modified Rankin Scale
[mRS] 0-3) and unfavorable (mRS 4-6). We (i) studied the natural course of NLR in
ICH, (ii) analyzed parameters associated with NLR on admission (NLROA), and (iii)
evaluated the clinical impact of NLR on mortality and functional outcome.
RESULTS: The median NLROA of the entire cohort was 4.66 and it remained stable
during the entire hospital stay. Patients with NLR >=4.66 showed significant
associations with poorer neurological status (National Institute of Health Stroke
Scale [NIHSS] 18 [9-32] vs. 10 [4-21]; p < 0.001), larger hematoma volume on
admission (17.6 [6.9-47.7] vs. 10.6 [3.8-31.7] mL; p = 0.001), and more
frequently unfavorable outcome (mRS 4-6 at 3 months: 317/427 [74.2%] vs. 275/428
[64.3%]; p = 0.002). Patients with an NLR under the 25th percentile (NLR <2.606)
compared to patients with NLR >2.606 - presented with a better clinical status
(NIHSS 12 [5-21] vs. 15 [6-28]; p = 0.005), lower hematoma volumes on admission
(10.6 [3.6-30.1] vs. 15.1 [5.7-42.3] mL; p = 0.004) and showed a better
functional outcome (3 months mRS 0-3: 82/214 [38.3%] vs. 185/641 [28.9%]; p =
0.009). Patients associated with high NLR (>=8.508 = above 75th-percentile)
showed the worst neurological status on admission (NIHSS 21 [12-32] vs. 12 [5
23]; p < 0.001), larger hematoma volumes (21.0 [8.6-48.8] vs. 12.2 [4.1-34.9] mL;
p < 0.001), and higher proportions of unfavorable functional outcome at 3 months
(mRS 4-6: 173/214 vs. 418/641; p < 0.001). Further, NLR was linked to more
frequently occurring infectious complications (pneumonia 107/214 vs. 240/641; p =
0.001, sepsis: 78/214 vs. 116/641; p < 0.001), and increased c-reactive-protein
levels on admission (p < 0.001; R2 = 0.064). Adjusting for the above-mentioned
baseline confounders, multivariable logistic analyses revealed independent
associations of NLROA with in-hospital mortality (OR 0.967, 95% CI 0.939-0.997; p
= 0.029). CONCLUSIONS: NLR represents an independent parameter associated with
increased mortality in ICH patients. Stroke physicians should focus intensely on
patients with increased NLR, as these patients appear to represent a population
at risk for infectious complications and increased short-mortality. Whether these
patients with elevated NLR may benefit from a close monitoring and specially
designed therapies should be investigated in future studies.
PMID- 28419990
TI - Effects of Estradiol on Autophagy and Nrf-2/ARE Signals after Cerebral Ischemia.
AB - BACKGROUND/AIMS: Estradiol (EST) reduces the risk of stroke and decreases the
incidence and progression of the disease because of its neuroprotective roles in
inhibiting cell death that occurs in response to a variety of neuronal stimuli
such as inflammation and oxidative stress. In this study, we determined the role
played by autophagy and Nrf2-ARE signal pathways in the hippocampus regions in
modulating cerebral ischemia under different EST conditions. METHODS: Western
blot analysis and ELISA were used to determine the protein expression of
autophagy and Nrf2-ARE pathways; and the levels of pro-inflammatory cytokines
(PICs) and a key marker of oxidative stress. RESULTS: Lacking of EST amplifies
autophagy and attenuates Nrf2-ARE pathway in the hippocampus CA1 region. Blocking
autophagy alleviates neurological deficits following cerebral ischemia with
lacking of EST levels and the effects of autophagy are associated with PIC and
oxidative stress. CONCLUSIONS: EST influences the protein expression of autophagy
and Nrf2-ARE signaling in the brain, which is linked to the pathophysiological
processes of PICs and oxidative stress. Moreover, inhibition of autophagy plays a
beneficial role in modulating neurological deficits after cerebral ischemia
observed under conditions of a lower level of EST.
PMID- 28419991
TI - Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal
Damage in a Rat Model of Vascular Dementia.
AB - OBJECTIVES: This study was intended to investigate whether treatment with
resveratrol and melatonin alone or in combination can exert neurorestorative
effects in a rat model of vascular dementia. METHODS: Briefly, male Wistar rats
were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by
surgery. After 4 weeks, the cognitive deficits were assessed using the Morris
water maze and novel object recognition tests. The biochemical parameters of
oxidative stress and inflammation were also assessed. RESULTS: Rats in the BCCAO
group showed cognitive deficits, accompanied by oxidonitrosative stress,
neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in
the hippocampus region. Moreover, the acetylcholinesterase activity in the
hippocampus was found to be increased in the BCCAO group compared to the sham
group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg)
alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a
significant improvement in the cognitive deficits induced by BCCAO, accompanied
by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion
in the hippocampus region. Additionally, the treatment with melatonin and
resveratrol significantly decreased acetylcholinesterase activity compared to in
the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of
hippocampal protein. CONCLUSION: These results emphasize that coadministration of
melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia
through changes in BDNF expressions.
PMID- 28419992
TI - Extended Small-Dose Platelet Transfusions in Multitransfused Hemato-Oncological
Patients: A Single-Center Experience.
AB - BACKGROUND: Refractoriness to platelet transfusion, prevalent among 15-20% of
hemato-oncological patients, is associated with multitransfusions and inferior
outcomes. We evaluated the effectiveness of extended slow-dose transfusion (ESDT)
in increasing platelet increments in multitransfused patients. METHODS: Patients
treated after the implementation of ESDT were compared with historical controls
treated with standard single-donor platelet (SDP) transfusions. Cohorts of early
and late recipients were assembled for comparison, i.e. the 8th or 9th and 11th
platelet unit per patient, respectively. Patients in the ESDT group received
transfusions equal to half an SDP unit, administered over 4 h. Effectiveness was
defined as a higher corrected count increment (CCI) at 1, 12, and 24 h after
transfusion. RESULTS: In the early-recipients cohort, 24-h-posttransfusion
increments were available for 29 ESDT patients and 6 standard patients, and did
not differ significantly between the groups (p = 0.078). The 24-h-posttransfusion
increment was available for 20 ESDT patients and 7 standard patients in the late
recipients cohort. The CCI was significantly higher in the ESDT group (p =
0.042). ABO compatibility improved the CCI (p = 0.01). CONCLUSIONS: ESDT
demonstrated slightly higher increments at 24 h after transfusion in late
recipients, suggesting this could be a cost-effective approach for the treatment
of thrombocytopenic multitransfused hemato-oncological patients.
PMID- 28419993
TI - Reduction in Peripheral CD19+CD24hCD27+ B Cell Frequency Predicts Favourable
Clinical Course in XELOX-Treated Patients with Advanced Gastric Cancer.
AB - BACKGROUND: Accumulating evidence suggests that regulatory B cells (Bregs) play
an important role in modulating the immune response to tumours. Our previous
study indicated that a small percentage of peripheral CD19+CD24hCD27+ Breg cells
slowed gastric cancer progression in XELOX-treated patients. Here, we further
investigated the relationship between dynamic changes in circulating Breg cells
and the clinical course in XELOX-treated gastric cancer patients. METHODS: A
total of 52 patients with advanced gastric cancer were enrolled in this study.
The frequencies of CD19+CD24hCD27+ cells in peripheral blood were tested before
(as a baseline) and 9 weeks after administration of oxaliplatin and capecitabine
(XELOX). The primary endpoint of the study was progression-free survival time
(PFS) of the patients. The overall survival (OS) and adverse events of
chemotherapy were also recorded. RESULTS: The median PFS of patients was 6 months
(95% CI, 5.27-6.73) with effective rate of 46.2%. The percentage of
CD19+CD24hCD27+ cells in lymphocytes ranged from 0.007% to 1.94%, with a median
value of 0.45%. The median percentage of CD19+CD24hCD27+ lymphocytes was 0.59%
(0.01%-6.02%) 9 weeks after treatment. There were no significant differences for
this index. However, the patients with decreased Breg frequencies after XELOX
treatment had a longer PFS time (7.0 months vs. 5.0 months, p=0.01) than those
with increased Breg frequencies. CONCLUSION: Patients with downtrend of
CD19+CD24hCD27+ B lymphocytes during early stages of chemotherapy relative to
their initial values had longer PFS times, and this could be used to predict the
efficacy of chemotherapy and help physicians adjust treatments accordingly.
PMID- 28419994
TI - Degradation of Mcl-1 through GSK-3beta Activation Regulates Apoptosis Induced by
Bufalin in Non-Small Cell Lung Cancer H1975 Cells.
AB - BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often
overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to
induce apoptosis in various tumor cells. However, there is no report showing that
bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation
was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis
was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression
of apoptosis-associated proteins in H1975 cells was detected by western blotting.
The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation
assay. RESULTS: Cell growth was inhibited by bufalin in a time and dose-dependent
manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades
and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished
bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA
expression in H1975 cells, but strongly promoted Mcl-1 protein degradation.
Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and
blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect
NOXA protein levels, but downregulated the expression of p-GSK-3beta. GSK-3
inhibitor and GSK-3beta siRNA resulted in increased levels of Mcl-1 and reversed
the bufalin-induced Mcl-1 degradation. CONCLUSION: Bufalin induced cell apoptosis
in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of
Mcl-1 via GSK-3beta activation was involved in bufalin-induced apoptosis.
PMID- 28419995
TI - Hemolytic Uremic Syndrome and Kidney Transplantation: A Case Series and Review of
the Literature.
AB - BACKGROUND: Hemolytic uremic syndrome (HUS) can be triggered by Shiga toxin
producing Escherichia coli (STEC) infection or it can be defined as atypical HUS
(aHUS) if it is related to uncontrolled complement activation. aHUS is
characterized by a high incidence of recurrence after kidney transplantation, and
it can also occur de novo in transplant recipients. Eculizumab is used both to
prevent and to treat aHUS following kidney transplantation. In this paper, we
report our centre experience and we present 4 cases of HUS in patients who
underwent kidney transplantation. METHODS: This is a single-center experience
about HUS development in transplanted patients. RESULTS: Patient 1 with end-stage
renal disease (ESRD) due to STEC-HUS undergoing kidney transplantation without
prophylactic therapy with eculizumab. Patient 2 with HUS secondary to an episode
of diarrhea at 8 years old. After a slow progression to ESRD, she underwent
kidney transplantation and she received prophylactic therapy with eculizumab due
to the presence of anti-complement factor H antibodies. Patient 3 underwent pre
emptive living donor ABO-incompatible kidney transplantation and developed HUS
secondary to antibody-mediated rejection. Patient 4 developed de novo HUS 16
years after kidney transplantation without a known cause. CONCLUSION: The correct
diagnosis of HUS and the identification of the complement component alterations
in case of aHUS are important parameters required to predict the risk of post
transplant recurrence of the disease. In the cases we reported, eculizumab has
been found to be effective both to prevent and to treat aHUS following kidney
transplantation.
PMID- 28419996
TI - Polydimethyl Siloxane as an Internal Tamponade for Vitreoretinal Surgery.
AB - PURPOSE: To report the efficacy and safety of polydimethyl siloxane (Siluron
Xtra(r)) as an internal tamponade. DESIGN: Audit and adverse event screening of
procedures (March 2014-2015). METHODS: Patients who had undergone vitreoretinal
procedures with Siluron Xtra(r) tamponade were retrospectively analysed with
respect to anatomical outcome, visual outcomes, and perioperative complications,
in particular intraocular pressure. INCLUSION CRITERIA: all patients who had
undergone Siluron Xtra(r) tamponade. EXCLUSION CRITERIA: No cases were excluded;
however, there were no paediatric or pregnant patients within this cohort. All
vitreoretinal cases were included, including retinal detachments, but also
trauma, endophthalmitis, and intraocular foreign bodies. RESULTS: Twenty-eight
patients had polydimethyl siloxane as an intraocular tamponade; 24 retinal
detachments (83% complicated by proliferative vitreoretinopathy >=grade C), 12
had previous failed surgery, and 4 had procedures for intraocular lymphoma,
endophthalmitis, or trauma. Follow-up was 14-20 months, and mean duration of
tamponade was 6.8 months (3-12 months). Anatomical success was 79% after
polydimethyl siloxane injection, 58% 3 months following removal (14/24), 5 remain
with long-term tamponade, and 5 with redetachment under tamponade required
further intervention. Five required topical anti-glaucomatous agents, and 1
following trauma required glaucoma surgery. Cataract developed in 3/6 phakic
patients, and visible emulsification occurred in a single patient. CONCLUSION:
Polydimethyl siloxane seems to be an acceptable alternative tamponade agent for
the management of complex retinal detachments with comparable anatomical success
and comparable rates of raised intraocular pressure to other low-viscosity
silicone oil agents, but more importantly, with a lower rate of emulsified oil
related complications, which is important particularly for cases requiring long
term tamponade.
PMID- 28419997
TI - Examining the Causal Role of Leptin in Alzheimer Disease: A Mendelian
Randomization Study.
AB - BACKGROUND: Observational evidence regarding the role of leptin in Alzheimer
disease (AD) is conflicting. We sought to determine the causal role of
circulating leptin and soluble plasma leptin receptor (sOB-R) levels in AD using
a separate-sample Mendelian randomization study. METHODS: Single nucleotide
polymorphisms (SNPs) independently and solely predictive of log-transformed
leptin (rs10487505 [LEP], rs780093 [GCKR], rs900400 [CCNL1], rs6071166 [SLC32A1],
and rs6738627 [COBLL1]) and of sOB-R (rs1137101 [LEPR], rs2767485 [LEPR], and
rs1751492 [LEPR]) levels (ng/mL) were obtained from 2 previously reported genome
wide association studies. We obtained associations of leptin and sOB-R levels
with AD using inverse variance weighting with fixed effects by combining Wald
estimates for each SNP. Sensitivity analyses included using weighted median and
MR-Egger methods and repeating the analyses using only SNPs of genome-wide
significance. RESULTS: Using inverse variance weighting, genetically predicted
circulating leptin levels were not associated with AD, albeit with wide
confidence intervals (CIs): odds ratio (OR) 0.99 per log-transformed ng/mL; 95%
CI 0.55-1.78. Similarly, the association of sOB-R with AD was null using inverse
variance weighting (OR 1.08 per log-transformed ng/mL; 95% CI 0.83-1.41). Results
from our sensitivity analyses confirmed our findings. CONCLUSIONS: In this first
Mendelian randomization study estimating the causal effect of leptin on AD, we
did not find an effect of genetically predicted circulating leptin and sOB-R
levels on AD. As such, this study suggests that leptin is unlikely to be a major
contributor to AD, although the wide CIs preclude a definitive assessment.
PMID- 28419998
TI - Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin
Chemotherapy.
AB - BACKGROUND AND AIMS: Several studies have indicated that cisplatin (cis
diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC).
However, the underlying cofactors affecting the increased urinary excretion
remain unclear. The present study was performed to evaluate the dynamics of LC in
plasma and urine after CDDP chemotherapy and to examine the relations with
clinical parameters, such as gender, body mass index (BMI), and renal function.
METHODS: Twenty-two patients treated with CDDP therapy were selected. Blood and
urine samples were taken from patients before starting CDDP treatment (day 0), on
the next day (day 1), and on the seventh day (day 7). We measured plasma and
urine concentrations of total, free, and acyl-LC, and examined the relationships
with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular
filtration rate, and change in creatinine concentration after CDDP
administration. RESULTS: Both urinary and plasma concentrations of 3 types of LC
increased markedly on day 1 and subsequently reverted to the pre-CDDP level on
day 7. There was a positive correlation between the % changes in plasma and urine
LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant
relations were seen in other clinical parameters. CONCLUSIONS: CDDP transiently
increased plasma LC levels. The mechanism seemed to involve recruitment for
marked urinary loss of LC. However, these changes in plasma and urinary LC levels
were not related to clinical factors, suggesting that the dynamics of LC were
independent of preexisting physical parameters.
PMID- 28419999
TI - Gender Differences and Stroke Outcomes.
PMID- 28420000
TI - (-)-Epicatechin Suppresses Angiotensin II-induced Cardiac Hypertrophy via the
Activation of the SP1/SIRT1 Signaling Pathway.
AB - BACKGROUND/AIMS: Flavonol (-)-epicatechin (EPI) is present in high amounts in
cocoa and tea products, and has been shown to exert beneficial effects on the
cardiovascular system. However, the precise mechanism of EPI on cardiomyocyte
hypertrophy has not yet been determined. In this study, we examined whether EPI
could inhibit cardiac hypertrophy. METHODS: We utilised cultured neonatal mouse
cardiomyocytes and mice for immunofluorescence, immunochemistry, qRT-PCR, and
western blot analyses. RESULTS: 1uM EPI significantly inhibited 1uM angiotensin
II (Ang II)-induced increase of cardiomyocyte size, as well as the mRNA and
protein levels of ANP, BNP and beta-MHC in vitro. The effects of EPI were
accompanied with an up-regulation of SP1 and SIRT1, and were abolished by SP1
inhibition. Up-regulation of SP1 could block Ang II-induced increase in
cardiomyocyte size, as well as the mRNA and protein levels of ANP, BNP and beta
MHC, and increase the protein levels of SIRT1 in vitro. Moreover, 1 mg/kg body
weight/day EPI significantly inhibited mouse cardiac hypertrophy induced by Ang
II, which could be eliminated by SP1 inhibition in vivo. CONCLUSION: Our data
indicated that EPI inhibited AngII-induced cardiac hypertrophy by activating the
SP1/SIRT1 signaling pathway.
PMID- 28420001
TI - Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced
Histone H3 Lysine9 Dimethylation in BEAS-2B Cells.
AB - BACKGROUND: Nickel compounds are well-established human carcinogens with weak
mutagenic activity. Histone methylation has been proposed to play an important
role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT)
decreases histone methylation in several cancer cells by altering the cellular
ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the
role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS
2B cells were exposed to different concentrations of nickel chloride (NiCl2) for
72 h or 200 MUM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9)
mono-, di-, and trimethylation and NNMT protein levels were measured by western
blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen
activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR
analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+) to
reduced NAD (NADH) and SAM/SAH ratio were determined. RESULTS: Exposure of BEAS
2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the
expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT
repression at both the protein and mRNA levels. Furthermore, over-expression of
NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio.
Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the
nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2.
CONCLUSIONS: These findings indicate that the repression of NNMT may underlie
nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.
PMID- 28420002
TI - Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China.
AB - BACKGROUND: Psoriasis is an autoimmune disease with genetic and environmental
factors. Based on the roles of STATs (signaling transducers and activators of
transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are
associated with psoriasis. OBJECTIVES: To study the association between STAT gene
polymorphisms and psoriasis in the northeastern Chinese population. METHODS:
Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769,
rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011
and rs3024974 in STAT6, using SNaPshot methods. The genotype, allele, and
haplotype frequencies were compared between 400 psoriasis patients and 398
healthy individuals in northeastern China. RESULTS: rs744166GG in STAT3 and
rs7574865TT in STAT4 had higher frequencies in the case than the control group,
suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05).
Three haplotypes (H3, H6, and H7) were found to be associated with psoriasis in
the study (p < 0.05). CONCLUSIONS: These results indicate a role of STAT genes in
the pathogenesis of psoriasis.
PMID- 28420003
TI - Retrospective Analysis of the Risk Factors for Grade IV Neutropenia in
Oesophageal Cancer Patients Treated with a Docetaxel, Cisplatin, and 5
Fluorouracil Regimen.
AB - BACKGROUND: Previous Japanese trials of the docetaxel, cisplatin, and 5
fluorouracil regimen for oesophageal cancer have demonstrated that a large
proportion of patients also develop grade IV neutropenia. Our aim was to examine
the risk factors for neutropenia in patients treated with this regimen. METHODS:
We retrospectively analysed the risk factors for developing grade IV neutropenia
in 66 patients with oesophageal cancer using a multivariate analysis. RESULTS:
After administering the docetaxel, cisplatin, and 5-fluorouracil regimen, 49
patients (74.2%) developed grade IV neutropenia. Grade IV neutropenia was
significantly associated with platelet count (p < 0.01), alanine transaminase
level (p = 0.05), and proton-pump inhibitor administration (p < 0.05). Receiver
operating characteristic curve analysis confirmed a platelet count of 290 *
103/MUL as the optimal diagnostic cut-off value for grade IV neutropenia. The
receiver operating characteristic area for grade IV neutropenia was increased by
including patients that were administered a proton-pump inhibitor and alanine
transaminase level (updated model; sensitivity and specificity, 75.5 and 88.2%,
respectively). CONCLUSIONS: Our findings suggest that a platelet count is the
most significant predictor of grade IV neutropenia.
PMID- 28420004
TI - Hearing Loss and Risk of Mild Cognitive Impairment and Dementia: Findings from
the Singapore Longitudinal Ageing Study.
AB - AIM: To investigate the associations between hearing loss and prevalent and
incident mild cognitive impairment (MCI), dementia and MCI or dementia (all
cases). METHODS: Cross-sectional and longitudinal analyses of baseline and follow
up data were performed in a population-based cohort. The baseline sample of 2,599
adults aged >=55 included 1,515 cognitively normal subjects who were followed up
to 8 years. Hearing loss at baseline was determined by the whispered voice test,
and MCI and dementia by Mini-Mental State Examination screening, Clinical
Dementia Rating scale, neurocognitive tests, MRI, and panel consensus diagnosis.
RESULTS: Hearing impairment was associated with increased prevalence of dementia
(odds ratio = 3.63, 95% confidence interval [CI] 1.16-11.4, p = 0.027) but not
MCI alone or all cases of MCI or dementia, adjusted for sex, age, ethnicity,
education, central obesity, hypertension, diabetes, dyslipidemia, smoking,
alcohol, leisure time activity, cardiac diseases, and depressive symptoms. Among
participants who were cognitively normal at baseline, those with hearing
impairment were more likely to develop MCI or dementia (hazard ratio [HR] = 2.30,
95% CI 1.08-4.92, p = 0.032). Hearing loss was associated with elevated but
statistically nonsignificant estimates of adjusted HR (1.85, 95% CI 0.78-4.40)
for incident MCI alone. CONCLUSIONS: Hearing loss is independently associated
with prevalent dementia and incident MCI or dementia.
PMID- 28420005
TI - Thiazide-Associated Hyponatremia: A Major Dilemma Affecting Treatment.
PMID- 28420006
TI - Increased Visfatin Expression Is Associated with Nuclear Factor-kappaB in Obese
Ovalbumin-Sensitized Male Wistar Rat Tracheae.
AB - OBJECTIVE: To investigate the effects of diet-induced obesity on the expression
of nuclear factor-kappaB (NF-kappaB) and visfatin messenger RNA in male Wistar
rats' tracheae after sensitization with ovalbumin (OVA). MATERIALS AND METHODS:
Twenty male Wistar rats were divided into 4 groups (n = 5 for each group), which
included a control group fed a normal diet (ND) and groups fed normal diet, OVA
sensitized (S+ND); high-fat diet (HFD) only (diet-induced obesity); and high-fat
diet, OVA-sensitized (S+HFD). All animals were fed for 8 weeks with standard chow
or a high-fat diet, and then were sensitized and challenged with OVA or saline
for another 4 weeks as per the above groups. The rats were anesthetized, after
which the necks were exposed and the tracheae isolated and examined for
expression levels of NF-kappaB and visfatin mRNA with the real-time polymerase
chain reaction method. Data were compared between the different groups using one
way analysis of variance. RESULTS: The expression level of NF-kappaB mRNA in the
S+HFD group was 2.67, which was statistically higher than the levels in the ND
(0.96; p = 0.001), S+ND (1.86; p = 0.05), and HFD (1.26; p = 0.001) groups. Also,
the visfatin mRNA expression level in the S+HFD group was 4.21, which was higher
than the levels in the ND (0.92), S+ND (1.79), and HFD (2.20) (p = 0.001) groups.
CONCLUSION: In this study, the expression levels of NF-kappaB and visfatin were
markedly higher in the S+HFD group in comparison to the other groups. These
findings indicate that alternative signaling pathways might be activated in diet
induced obesity associated with the OVA-sensitized animal model and could be
responsible for possible altered sensitization phenotype.
PMID- 28420007
TI - Accessory Spleen in the Greater Omentum: Embryology and Revisited Prevalence
Rates.
AB - PURPOSE: To investigate in a large sample the prevalence rates of accessory
spleens located in the greater omentum and to explain the embryological
background and the vascular supply of this rare congenital disorder. METHODS:
Evaluation of the presence of accessory spleens located in the greater omentum
was performed in 5 different international anatomical centers investigating a
total of 1,045 body donors. Arterial and venous blood supply and the precise
location of the respective vasculature within the splenic ligaments are described
based on dissection of this rare condition in a male specimen. RESULTS: The
reported prevalence rates from 5 different centers were: 0.5% (out of 380 body
donors), 0% (out of 230 donors), 0% (out of 200 donors), 2% (out of 200 donors),
and 0% (out of 35 donors). The cumulative prevalence rate obtained from 1,045
anatomical dissections was 0.6%. The identified accessory spleen measured 3 * 3 *
2.5 cm and was located in the left upper abdominal quadrant. A vascular stag 7.5
cm in length was identified within the gastro-splenic ligament, containing an
artery and a vein piercing the greater omentum from posterior. CONCLUSION: An
accessory spleen located in the greater omentum is a rare congenital disorder.
Physicians should be aware of the fact that in patients without any
representative symptom history a nodular mass located within the greater omentum
could be an accessory spleen.
PMID- 28420008
TI - C-reactive protein and cold-pressor tolerance in the general population: the
Tromso Study.
AB - The aim of this study was to examine whether increases in severity of subclinical
inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased
experimental pain sensitivity, measured by cold-pressor tolerance, and to test
whether this relationship is independent of chronic pain. A large population
based study from 2007 to 2008, the sixth Tromso Study, provided data from 12,981
participants. For the present analysis, complete data for 10,274 participants
(age: median 58 years) were available. The main outcome measure was cold-pressor
tolerance, tested by placing the dominant hand in circulating cold water (3
degrees C) for a maximum of 106 seconds. Cox proportional hazard models, treating
hand withdrawal during the cold-pressor test as the event and enduring the full
test time as censored data, were used to investigate the relationship between hs
CRP levels (<=3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model
was controlled for age, sex, education, body mass index, smoking status, alcohol
consumption, emotional distress, statin usage, and self-reported presence of
chronic pain. Additional analysis was performed in participants without chronic
pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance
(hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001),
adjusted for age and sex. This relationship remained essentially unaltered after
controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001),
as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P <
0.001). The present data show that subclinical inflammation is related to
increased pain sensitivity, suggesting a potential role of inflammation in
experimental pain which may be of importance for the development of clinical
pain.
PMID- 28420009
TI - Temporal summation and motor function modulation during repeated jaw movements in
patients with temporomandibular disorder pain and healthy controls.
AB - Temporal summation of nociceptive inputs may be an important pathophysiological
mechanism in temporomandibular disorders (TMD) pain; however, it remains unknown
how natural jaw function relates to underlying pain mechanisms. This study
evaluated changes in pain and movement patterns during repeated jaw movements in
patients with painful temporomandibular joints (TMJ) compared with healthy
controls. Twenty patients with TMD with TMJ pain, and an anterior disk
displacement without reduction and 20 age- and gender-matched healthy volunteers
were included. Participants performed 20 trials (4 * 5 sessions) of standardized
and repeated mandibular movements, and scored the movement-associated pain
intensity on 0 to 10 numeric rating scale in addition to measurements of jaw
movements. Patients with TMJ pain reported higher baseline pain compared to the
control group for all types of jaw movements (P = 0.001) and significant
increases in numeric rating scale pain scores by repetition of jaw movements (P <
0.001), which was not observed in the control group (P > 0.05). Jaw total opening
distance (P = 0.030), maximum opening velocity (P = 0.043) and average closing
velocity (P = 0.044) in the TMJ pain group were significantly reduced during the
repeated movements. In the control group, however, total opening distance (P =
0.499), maximum opening velocity (P = 0.064), and average closing velocity (P =
0.261) remained unchanged, whereas average opening velocity (P = 0.040) and
maximum closing velocity (P = 0.039) increased. The study demonstrates that
repeated jaw movements constitute a sufficient and adequate stimulation for
triggering temporal summation effects associated with significant inhibition of
motor function in painful TMJs. These findings have practical implications for
diagnosis of TMD pain and for more mechanism-driven management protocols in the
future.
PMID- 28420010
TI - Consumption of Methamphetamine during Pregnancy - Transgenerational Substance
Misuse?
PMID- 28420011
TI - Noninvasive Ventilation in Newborns <= 1,500 g after Tracheal Extubation:
Randomized Clinical Trial.
PMID- 28420012
TI - Vitamin B6-Responsive Epilepsy due to a Novel KCNQ2 Mutation.
AB - Mutations in KCNQ2, encoding for subunits of potassium channels, are known to
cause neonatal epileptic encephalopathy (NEE). Therapeutic options for these
children are often limited. Recently, there are indications that some patients
with KCNQ2 NEE show seizure response to vitamin B6 (VB6) therapy. We present a
young infant with severe KCNQ2 encephalopathy resulting from a novel de novo
mutation (c.1023G>C; p.(Gln341His)). In our patient, VB6 responsiveness could be
demonstrated clearly by remarkable seizure-response to VB6 therapy and seizure
exacerbation to discontinuation of VB6 therapy. The pathophysiology of VB6
response in potassium channel mutations is not understood. Some hypothetical
mechanisms are currently in discussion. To identify the group of patients who
benefits from VB6 therapy, further investigations are necessary.
PMID- 28420013
TI - [Febrile Urinary Tract Infections: When are they an Emergency?]
PMID- 28420014
TI - [Febrile Urinary Tract Infections: When are they an Emergency?]
AB - Urinary tract infections should be suspected in every febrile infant until proven
otherwise. While older children and adolescents mostly present with classical
features such as dysuria, flank pain and/or abdominal pain, secondary enuresis or
pollakiuria, diagnosing infants or newborns, who are incapable of describing or
pinpointing pain, can be much more challenging. As such, an infection with
gradual and subtle onset may result in fulminant disease and emergency
situations. In children with urinary tract infections and known mechanical or
functional obstructions of the urinary tract, adequate drainage of the infected
urinary tract may be necessary (e. g. nephrostomy, ureteral stent or
transurethral catheter).
PMID- 28420015
TI - [Editor's Comment].
PMID- 28420016
TI - ?
PMID- 28420017
TI - ?
PMID- 28420018
TI - ?
PMID- 28420019
TI - ?
PMID- 28420020
TI - [Harvesting Grafts for Reconstruction of the Tympanic Membrane].
PMID- 28420021
TI - ?
PMID- 28420022
TI - [Severe Bleeding from the Middle Ear Cavity after Myringotomy: Review Based on a
Case Report].
AB - Report of a rare case of severe bleeding from the middle ear cavity after
myringotomy. On the basis of the case report, the procedure for such bleeding is
discussed in the context of the literature. A 6-year-old boy received a revision
myringotomy in an ambulant setting. During the procedure a severe bleeding
occurred. The external auditory canal was adequately packed. The patient was
extubated and transferred to the clinic as an emergency. Computer tomography of
the temporal bone showed the anatomical variant of a dehiscent high jugular bulb,
which had been injured. Because no rebleeding occurred, the packing of the ear
canal was removed and an explorative tympanoscopy was performed on the third
postoperative day. When the tympanomeatal flap was lifted, the defect in the
jugular bulb was found. The lesion was covered with Tutopatch(r) pads and fibrin
glue and the auditory canal was packed again. After removal of the packing three
weeks postoperatively a properly healed situs was found. No further measures were
taken. The injury of a dehiscent jugular bulb in the course of ear surgeries
leads to a massive hemorrhage. The case describes the diagnostic and therapeutic
procedure for this relatively rare but severe complication.
PMID- 28420023
TI - [A Blocked Frontal Sinus with Orbital Swelling].
PMID- 28420024
TI - [From the Expert's Office: Resection of Thyroid Tissue Instead of Zenker's
Diverticulum - A Medical Malpractice].
PMID- 28420025
TI - [Recent Developments Towards Molecularly Targeted Therapy of Head and Neck
Cancer].
PMID- 28420026
TI - ?
PMID- 28420027
TI - ?
PMID- 28420028
TI - Intrauterine Ultrasound-Guided Laser Coagulation of the Feeding Artery in Fetal
Bronchopulmonary Sequestration.
PMID- 28420029
TI - Interlobar Artery Resistive Index predicts Acute-on-Chronic Liver Failure
Syndrome in Cirrhotic Patients with Acute Decompensation.
AB - INTRODUCTION: Patients with acutely decompensated (AD) cirrhosis are at risk for
developing acute-on-chronic liver failure (ACLF) syndrome. This syndrome is
associated with a high short-term mortality rate. The aim of our study was to
identify reliable early predictors of developing ACLF in cirrhotic patients with
AD. PATIENTS AND METHODS: We assessed 84 cirrhotic patients admitted for AD
without ACLF on admission. We performed routine blood testing and detailed
ultrasound Doppler studies of systemic arteries and mayor abdominal veins and
arteries. We also calculated liver-specific and intensive care unit predictive
scores. The area under the ROC curve (AUROC) was calculated for all variables
that were significantly different between patients who developed ACLF and those
who did not. Sensitivity, specificity, positive and negative predictive values,
as well as diagnostic accuracy predicting the short-term development of ACLF were
determined. RESULTS: of the 84 patients, 23 developed ACLF whereas 61 did not.
In the univariate analysis, serum levels of creatinine and urea, prothrombin time
ratio, MELD score, portal vein and femoral artery flow velocity as well as the
renal and interlobar artery resistive indices (RI) were associated with the short
term development of ACLF. However, only interlobar artery RI had independent
predictive value in the multivariate analysis. The AUROC value for RI of the
interlobar arteries was 0.9971. CONCLUSION: On the first day of admission,
ultrasound measurement of the RI of the interlobar arteries recognizes with high
predictive accuracy those cirrhotic patients admitted with AD who will develop
ACLF during hospital admission.
PMID- 28420030
TI - Role of endoscopy in primary sclerosing cholangitis: European Society of
Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the
Liver (EASL) Clinical Guideline.
AB - 1 ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic
resonance cholangiography (MRC) should be preferred over endoscopic retrograde
cholangiopancreatography (ERCP).Moderate quality evidence, strong recommendation.
2 ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is
equivocal or contraindicated in patients with persisting clinical suspicion of
PSC. The risks of ERCP have to be weighed against the potential benefit with
regard to surveillance and treatment recommendations.Low quality evidence, weak
recommendation. 6 ESGE/EASL suggest that, in patients with an established
diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak
recommendation, low quality evidence. 7 ESGE/EASL suggest performing endoscopic
treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies)
of suspected significant strictures identified at MRC in PSC patients who present
with symptoms likely to improve following endoscopic treatment.Strong
recommendation, low quality evidence. 9 ESGE/EASL recommend weighing the
anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a
case-by-case basis.Strong recommendation, moderate quality evidence.Biliary
papillotomy/sphincterotomy should be considered especially after difficult
cannulation.Strong recommendation, low quality evidence. 16 ESGE/EASL suggest
routine administration of prophylactic antibiotics before ERCP in patients with
PSC.Strong recommendation, low quality evidence. 17 EASL/ESGE recommend that
cholangiocarcinoma (CCA) should be suspected in any patient with worsening
cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant
stricture, particularly with an associated enhancing mass lesion.Strong
recommendation, moderate quality evidence. 19 ESGE/EASL recommend ductal sampling
(brush cytology, endobiliary biopsies) as part of the initial investigation for
the diagnosis and staging of suspected CCA in patients with PSC.Strong
recommendation, high quality evidence.
PMID- 28420031
TI - The ventromedial hypothalamic nucleus in the zebra finch (Taeniopygia guttata):
Afferent and efferent projections in relation to the control of reproductive
behavior.
AB - Sex-specific mating behaviors occur in a variety of mammals, with the medial
preoptic nucleus (POM) and the ventromedial hypothalamic nucleus (VMH) mediating
control of male and female sexual behavior, respectively. In birds, likewise, POM
is predominantly involved in the control of male reproductive behavior, but the
degree to which VMH is involved in female reproductive behavior is unclear. Here,
in male and female zebra finches, a combination of aromatase immunohistochemistry
and conventional tract tracing facilitated the definition of two separate but
adjacent nuclei in the basal hypothalamus: an oblique band of aromatase-positive
(AR+) neurons, and ventromedial to this, an ovoid, aromatase-negative (AR-)
nucleus. The AR- nucleus, but not the AR+ nucleus, was here shown to receive a
projection from rostral parts of the thalamic auditory nucleus ovoidalis and from
the nucleus of the tractus ovoidalis. The AR- nucleus also receives an
overlapping, major projection from previously uncharted regions of the medial
arcopallium and a minor projection from the caudomedial nidopallium. Both the AR-
and the AR+ nuclei project to the intercollicular nucleus of the midbrain. No
obvious sex differences in either the pattern of AR immunoreactivity or of the
afferent projections to the AR- nucleus were observed. The significance of these
results in terms of the acoustic control of avian reproductive behavior is
discussed, and a comparison with the organization of VMH afferents in lizards
suggests a homologous similarity of the caudal telencephalon in sauropsids.
PMID- 28420032
TI - Identifying a subset of patients with DCIS who have a low likelihood of residual
disease at surgical excision following a core needle biopsy.
AB - BACKGROUND AND OBJECTIVES: Current randomized controlled trials are investigating
the outcomes of non-surgical treatment for patients with ductal carcinoma in situ
(DCIS). We sought to evaluate pre-operative factors associated with no residual
disease at definitive resection following a core needle biopsy (CNB) diagnosis of
DCIS. METHODS: Eight hundred and thirty-four operations for DCIS were performed
at our institution between January 2004 and October 2014. We evaluated patient
and biopsy tumor characteristics to determine pre-operative factors associated
with no residual disease at surgical resection using uni- and multivariable
analyses. RESULTS: Sixty-nine patients (8%) had no residual disease on final
pathology. On multivariable analysis, low- or intermediate-grade lesions, <1 cm
in size on mammography, and lesions where >=90% of calcifications were removed
correlated with finding no residual disease on final pathology, c-statistic 0.84.
Of the 14 patients with all three low-risk factors, 36% had no residual disease
on final pathology. CONCLUSIONS: Although our multivariable analysis performed
well, its clinical utility would be limited as we were unable to identify a
subset of patients with DCIS in whom the probability of finding no residual
disease is low enough to consider routine use of non-surgical management.
PMID- 28420033
TI - The current clinical knowledge on the treatment of gambling disorder: A summary.
AB - Gambling disorder (GD) is a topical problem in developed countries and may be
present in 1-3% of the general population. The pathophysiology of this disorder
is largely unknown but it shares similarities to other behavioral addictions.
Multiple neurotransmitter systems, including dopaminergic, serotonergic,
noradrenergic, glutamatergic, and opioidergic, have been implicated in GD. Based
on available articles, only the opioid antagonist naltrexone has been documented
to demonstrate clinical efficacy in multiple studies including double-blind
studies. Nalmefene, another opioid antagonist, may be active as well but its dose
response effect remains unclear. Contrarily, current test results do not support
the therapeutic use of any antidepressant drug. Some positive data has been made
available supporting the use of N-acetylcystein, but more studies are needed to
confirm this. No clear or definite information is currently available for other
drugs.
PMID- 28420034
TI - A fluorescence in situ hybridization-based screen allows rapid detection of
adverse cytogenetic alterations in patients with acute myeloid leukemia.
AB - In adult acute myeloid leukemia (AML), the karyotype of the leukemic cell is
among the strongest prognostic factors. The Medical Research Council (MRC) and
the European LeukemiaNet (ELN) classifications distinguish between favorable,
intermediate and adverse cytogenetic risk patients who differ in their treatment
response and overall survival. Conventional cytogenetic analyses are a mandatory
component of AML diagnostics but they are time-consuming; therefore, therapeutic
decisions in elderly patients are often delayed. We investigated whether a
screening approach using a panel of seven fluorescence in situ hybridization
(FISH) probes would allow rapid identification of adverse chromosomal changes. In
a cohort of 334 AML patients, our targeted FISH screening approach identified 80%
of adverse risk AML patients with a specificity of 99%. Incorporating FISH
screening into diagnostic workup has the potential to accelerate risk
stratification and treatment selection, particularly in older patients. This
approach may allow therapeutic decisions more quickly, which benefits both
patients and physicians and might save costs.
PMID- 28420035
TI - Prospective series of reconstruction of complex composite mandibulectomy defects
with double island free fibula flap.
AB - BACKGROUND: A double island free fibula (DIFF) flap can be used for
reconstruction of through-and-through or complex mandibulectomy defects, but
prospective studies are lacking. METHODS: Prospective analysis of all double skin
paddle fibula flaps performed from 2010 to 2016. RESULTS: Overall, 16 patients
underwent reconstruction with a DIFF flap (average age: 59.1 years). One patient,
who underwent a DIFF flap and developed osteoradionecrosis, requiring a second
flap. Thirteen patients were males, and 7 had a history of smoking, 13 had prior
radiation, and 14 had prior chemotherapy. The most common primary pathology was
squamous cell carcinoma (n = 13). Reconstruction using the DIFF was predominantly
for mandible reconstruction with one patient undergoing reconstruction following
a orbitomaxillectomy. Complications included infection (n = 2), hematoma (n = 1),
and donor site complications were limited. Two patients developed venous
congestion requiring re-exploration, and both flaps were successfully salvaged.
One patient lost the external skin paddle requiring a pectoralis muscle flap, and
there were no total flap losses. CONCLUSIONS: The DIFF flap is a reliable option
that can reconstruct complex composite defects often obviating the need for a
second free flap, thereby decreasing operating time, added donor site morbidity,
and the need for additional recipient vessels.
PMID- 28420036
TI - Dedifferentiated chondrosarcoma: A survival analysis of 159 cases from the SEER
database (2001-2011).
AB - BACKGROUND AND OBJECTIVES: Dedifferentiated chondrosarcoma is a rare malignancy
with reported 5-year overall survival rates ranging from 7% to 24%. The purpose
of this investigation is to determine the overall survival of dedifferentiated
chondrosarcoma in a modern patient series and how it is impacted by patient
demographics, tumor characteristics, and surgical treatment factors. METHODS:
This is a retrospective review of the Surveillance, Epidemiology, and End Results
(SEER) database from 2001 to 2011. Kaplan Meier analyses were used for overall
and disease-specific survival. Univariable and multivariable cox regression
models were used to identify prognostic factors. RESULTS: Five year overall- and
disease-specific survival was 18% (95% CI: 12-26%) and 28% (95% CI: 18-37%),
respectively. Individuals with extremity tumors had a worse prognosis than
individuals with a primary tumor in the chest wall or axial skeleton (HR 0.20,
95% CI: 0.07-0.56; P = 0.002 and HR 0.60, 95% CI: 0.36-0.99; P = 0.04,
respectively). Patients with AJCC stage III or IV disease (HR 2.51, 95% CI: 1.50
4.20; P = 0.001), tumors larger than 8 cm (HR 2.17, 95% CI: 1.11-4.27; P =
0.046), metastatic disease at diagnosis (HR 3.25, 95% CI: 1.98-5.33; P < 0.001),
and those treated without surgical resection (amputation: HR 0.43, 95% CI 0.23
0.80; P = 0.01; limb salvage/non-amputation resection: HR 0.41, 95% CI: 0.24
0.69; P = 0.001) had a significant increase in risk of mortality. CONCLUSIONS:
The overall prognosis of dedifferentiated chondrosarcoma is poor with a 5-year
overall survival of 18%. Patients with a primary tumor located in the chest wall
had a better prognosis. Tumors larger than 8 cm, presence of metastases at
diagnosis, and treatment without surgical resection were significant predictors
of mortality.
PMID- 28420037
TI - Does surgery or radiation provide the best overall survival in Ewing's sarcoma? A
review of the National Cancer Data Base.
AB - BACKGROUND AND OBJECTIVES: There is continuing debate regarding the ideal
modality for local control of the primary tumor for patients with Ewing's
sarcoma. The primary aim of this study is to investigate the impact of the method
of local control on overall survival in patients with Ewing's sarcoma. METHODS:
The National Cancer Data Base was used to identify patients <40 years of age with
high-grade Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was
performed at 2, 5, and 10 years. Factors with a level of significance of P < 0.1
at the 5-year time point were included in a multivariate Cox proportional hazards
model. RESULTS: Diminished 5-year survival was noted for patients with metastatic
disease, local control with radiation alone, age >=18 years, tumor size >8 cm,
and male sex while controlling for tumor site. Surgery alone was consistently the
method of local control that resulted in the highest overall survival.
CONCLUSIONS: Surgery alone resulted in the best overall survival for patients
with Ewing's sarcoma of bone. The results of this investigation provide support
to the approach of surgical resection with negative margins when possible.
PMID- 28420038
TI - Retrospective evaluation of coyote attacks in dogs: 154 cases (1997-2012).
AB - OBJECTIVE: To describe the clinical presentation and outcome of known attacks in
client-owned dogs caused by the common coyote, Canis latrans. DESIGN:
Retrospective observational study. SETTING: Private referral hospital. ANIMALS:
One hundred fifty-four client-owned dogs known to be attacked by coyotes.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records from a private
referral hospital from May 1997 through December 2012 were reviewed. Time of day
and month/season of year, signalment, body temperature, heart rate, respiratory
rate, body weight, location and severity of wounds inflicted, common injuries,
length of hospitalization, necessity of surgical wound repair under anesthesia,
antimicrobial use and mortality were recorded. Eighty-six percent of dogs
presenting following coyote attack weighed <10 kg. Overall mortality rate was
15.6%. Dogs with bite wounds to the thorax had the highest mortality at 21.3%.
Criteria for systemic inflammatory response syndrome (SIRS) based on admission
vital signs were met in 58.8% of dogs and the presence of SIRS was significantly
associated with mortality (P < 0.001). Common coyote-induced injuries included
rib fracture (38/154; 24.6%), pulmonary contusion (30/154; 19.4%), tracheal tear
(18/154; 11.6%), pneumothorax (16/154; 10.3%), abdominal wall hernia (9/154;
5.8%), and abdominal penetrating wounds (8/146; 5.5%). Dogs <10 kg were
significantly more likely to incur wounds to multiple body parts or sustain
abdominal penetrating wounds. The presence of rib fracture was significantly
associated with mortality. Frequency of coyote attacks over the time of this
study increased by 330%. CONCLUSIONS: Coyote attacks on dogs are a problem in
Southern California and are associated with substantial morbidity and mortality,
especially in dogs with wounds to the thorax. Aggressive management involving
surgical wound repair was associated with survival to discharge.
PMID- 28420039
TI - Utilizing Salmonella to treat solid malignancies.
AB - Despite intensive research into novel treatment strategies for cancer, it remains
the second most common cause of death in industrialized populations. Pancreatic
ductal adenocarcinoma (PDAC) is a highly aggressive disease with dismal
prognosis. Currently, surgical resection offers the best chance for extended
survival, yet recurrence remains high and is associated with poor outcome.
Systemic treatment has evolved from non-specific, cytotoxic chemotherapy to the
use of cancer-targeting agents, profoundly changing treatment approaches in the
metastatic and adjuvant settings. One promising approach, highlighted in this
review, uses the inherent capacity of Salmonella to colonize and eliminate solid
tumors.
PMID- 28420040
TI - Semi-end-to-end esophagojejunostomy after laparoscopy-assisted total gastrectomy
better reduces stricture and leakage than the conventional end-to-side procedure:
A retrospective study.
AB - BACKGROUND AND OBJECTIVE: Laparoscopy-assisted total gastrectomy (LATG) has not
gained popularity due to the technical difficulty of esophagojejunostomy (EJ) and
the high incidence of EJ-related complications. Herein, we compared two types of
EJ for Roux-en-Y reconstruction to determine whether semi-end-to-end (SETE) EJ is
more convenient than the end-to-side (ETS) procedure and is capable of reducing
stricture and leakage. METHODS: A total of 268 patients who underwent LATG with
Roux-en-Y reconstruction were included in this study. Two types of EJ were
applied for LATG: conventional ETS EJ and SETE EJ. The surgical outcomes and
postoperative complications were compared. RESULTS: The mean reconstruction time
in the SETE group was shorter than that in the ETS group (41.6 +/- 8.0 min vs
51.3 +/- 9.2 min, P = 0.000). The incidences of total EJ-related complications,
EJ leakage, and EJ stricture in the SETE group and ETS group were 1.1% (1/92) and
10.2% (18/176), 1.1% (1/92) and 4.0% (7/176), and 0 and 6.2% (11/176),
respectively. The incidence of total EJ-related complications in the SETE group
was lower than that of the ETS group (P = 0.006), and the incidence of EJ
stricture in the SETE group was lower than that of the ETS group (P = 0.034).
CONCLUSIONS: SETE EJ is more convenient than the conventional ETS procedure and
is associated with a shorter reconstruction time and a lower incidence of EJ
stricture and leakage.
PMID- 28420041
TI - [18 F]Nifene test-retest reproducibility in first-in-human imaging of
alpha4beta2* nicotinic acetylcholine receptors.
AB - : The aim of this study was to examine the suitability of [18 F]nifene, a novel
alpha4beta2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo
brain imaging in a first-in-human study. METHODS: Eight healthy subjects (4 M,4
F;21-69,44 +/- 21 yrs) underwent a [18 F]nifene positron emission tomography scan
(200 +/- 3.7 MBq), and seven underwent a second scan within 58 +/- 31 days.
Regional estimates of DVR were measured using the multilinear reference tissue
model (MRTM2) with the corpus callosum as reference region. DVR reproducibility
was evaluated with test-retest variability (TRV) and intraclass correlation
coefficient (ICC). RESULTS: The DVR ranged from 1.3 to 2.5 across brain regions
with a TRV of 0-7%, and did not demonstrate a systematic difference between test
and retest. The ICCs ranged from 0.2 to 0.9. DVR estimates were stable after 40
min. CONCLUSION: The binding profile and tracer kinetics of [18 F]nifene make it
a promising alpha4beta2* nAChR radiotracer for scientific research in humans,
with reliable DVR test-retest reproducibility.
PMID- 28420042
TI - Determination of reference intervals of acid-base parameters in clinically
healthy dogs.
AB - OBJECTIVE: To establish reference intervals for traditionally- and Stewart's
approach-determined acid-base parameters in a population of clinically healthy
dogs. DESIGN: Prospective study (June 2011-September 2012). SETTING: Veterinary
teaching hospital. ANIMALS: Two hundred twenty-four client-owned, clinically
healthy dogs. INTERVENTIONS: Blood was collected from the jugular vein and the
dorsal pedal artery. MEASUREMENTS AND MAIN RESULTS: In the whole blood samples,
pH, PCO2 , and PO2 were measured and HCO3- , standard and total bicarbonate, base
excess, oxygen content, and alveolar-arterial oxygen differences were calculated.
Plasma sodium, potassium, chloride, calcium, albumin, and lactate concentrations
were measured and the following parameters were calculated separately for venous
and arterial samples: anion gap, anion gap corrected for albumin and phosphate,
sodium chloride difference and ratio, chloride gap, strong ion difference, strong
ion gap, and unmeasured anions. CONCLUSION: Reference intervals for traditionally
and Stewart's approach-determined acid-base parameters were established for
venous and arterial blood in dogs.
PMID- 28420043
TI - [Alcohol consumption prevalence in civil servants].
AB - : Temporomandibular dysfunction syndrome (TMDS) includes a number of clinical
conditions involving the temporomandibular joint (TMJ), the muscles involved in
mastication, or both. The symptoms of TMDS include decreased mobility,
masticatory muscle pain, TMJ pain, functional alteration accompanied by articular
noises, myofascial pain or deviation of the mouth opening. Work with visual
display terminals (VDTs) has become widespread in the past several years and the
conditions associated with this type of work have been associated with the
appearance of certain musculoskeletal pathologies. Our objective was to conduct a
review of the scientific literature onthe possible association between TMDS and
work with VDTs. METHOD: A search of the literature in MEDLINE (PubMed), Cochrane
Plus Library, CINHAL, Scielo and Google Academic was performed.We included those
studies involving workers using VDTs and the outcome measures had to include
references to TMDS symptoms. RESULTS AND DISCUSSION: A total of 112 articles were
identified, of which finally 11 were selected for in-depth review. Given the
heterogeneity of the results and the nature of the studies, we conclude that
currently there is insufficient evidence to support a consistent relationship
between TMDS pathology and work with VDTs. There is insufficient evidence linking
the presence of TMDS with ergonomic and postural aspects, an association that
should not be totally ruled out from a pathophysiological point of view and
biological plausibility. Further studies are needed to better assess this
relationship.
PMID- 28420044
TI - Role of MMP-7 in the pathogenesis of systemic lupus erythematosus (SLE).
AB - Systemic lupus erythematosus (SLE) is a clinically heterogeneous chronic,
inflammatory autoimmune disorder. The association of MMP-7 and disease severity
is still unclear. A total of 150 SLE patients and matched healthy controls were
recruited for this study. Disease activity was scored according to SLEDAI (98
active and 52 inactive disease). Mean serum MMP-7 levels were significantly
higher in SLE patients than controls ( p < 0.001). Patients with active disease
showed higher levels (16.24 +/- 6.2 ng/ml) as against inactive disease (10.50 +/-
3.97 ng/ml) ( p <= 0.0001). Mean MMP-7 mRNA expression was significantly higher
in patients (RQ = 3.16 +/- 0.93) as compared to controls (RQ = 2.21 +/- 0.89, p =
0.006). A positive correlation between MMP-7 levels, mRNA expression and SLEDAI
score was observed ( r = 0.563, r = 0.427). The MMP-7 -181 G allele was found to
be significantly higher among SLE patients ( p < 0.0001). A significant
association was noted between MMP-7 -181 A/G +G/G genotypes with renal ( p =
0.0027) and CNS ( p = 0.0031) manifestations and anti-dsDNA autoantibodies ( p =
0.0312). Serum MMP-7 levels and mRNA expression were elevated in advanced stages
of SLE, indicating that MMP-7 is associated with disease activity in SLE.
PMID- 28420045
TI - Drug-induced lupus erythematosus mimicking lymphoma on 18F-FDG-PET/CT.
PMID- 28420046
TI - Anti-heparan sulfate antibody and functional loss of glomerular heparan sulfate
proteoglycans in lupus nephritis.
AB - Background The purpose of this study was to evaluate the features of heparan
sulfate proteoglycans (HSPGs) as agrins of the glomerular basement membrane (GBM)
and circulating anti-heparan sulfate (HS) antibodies in lupus nephritis,
comparing titers among the following groups: lupus nephritis (LN), non-renal
lupus, non-lupus nephritis, and healthy controls. Methods The stage of nephritis
was determined based on the kidney biopsy. Alcian blue staining and
immunohistochemical (IHC) staining for agrin were performed for histological
evaluation of GBM HSPGs in normal glomeruli, non-lupus membranous
glomerulonephritis (MGN), and lupus MGN. The results were used for measurement of
the serum anti-HS antibody titers using an enzyme-linked immunosorbent assay
(ELISA) in the following groups: 38 healthy controls, 38 non-lupus nephritis, 37
non-renal lupus, and 38 LN. Results Glomerulus HSPGs were stained bluish-green
along the GBM with Alcian blue. However, IHC staining against agrin was almost
completely negative in the lupus MGN group compared with the normal and non-lupus
MGN groups, which showed brown staining of GBM. A higher level of anti-HS IgG was
detected in LN compared with other groups, respectively. Higher titers were
associated with the presence of SLE and nephritis. A higher degree of proteinuria
normalized to glomerular filtration rate (eGFR) was observed in association with
higher anti-HS antibody titers in LN. Conclusion This study demonstrated a
functional loss of GBM HSPGs and higher levels of circulating anti-HS antibodies
as a characteristic feature of lupus nephritis, suggesting their involvement in
the pathogenesis of lupus nephritis and proteinuria.
PMID- 28420047
TI - Organ damage accrual and distribution in systemic lupus erythematosus patients
followed-up for more than 10 years.
AB - Objective The aim of this study was to determine the prevalence, predictors and
progression of organ damage in a monocentric cohort of systemic lupus
erythematosus patients with a long follow-up. Organ damage was assessed by the
Systemic Lupus International Collaborating Clinics Damage Index one year after
diagnosis and every five years. Disease activity was measured by the systemic
lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the
follow-up. Univariate and multivariable analyses were used to detect items
associated with damage. A total of 511 systemic lupus erythematosus patients (92%
females, 95% Caucasian), prospectively followed from 1972 to 2014, were included.
Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up
of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7%
developed mild/moderate damage, while 19.5% showed severe damage. Damage was
evident in 40% of 511 patients one year after diagnosis, and its prevalence
linearly increased over time. Longer disease duration, higher SLEDAI, severe
Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated
with organ damage. No associations between damage and autoantibodies, including
anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway,
antiphospholipid syndrome and anticardiolipin antibodies predicted the
development of neuropsychiatric damage. The ocular, musculoskeletal and
neuropsychiatric systems were the most frequently damaged organs, with a linear
increase during follow-up. Conclusion A high rate of moderate and severe damage
has been detected early in a wide cohort of young lupus patients, with a linear
trend of increase over time. Disease activity and long duration of disease
predict damage, while antiphospholipid antibodies play a role in determining
neuropsychiatric damage.
PMID- 28420048
TI - Pincer nail in a lupus patient.
AB - Pincer nail is a transverse overcurvature of the nail plate that may appear in
association with a variable number of diseases. We present a case report of a 28
year-old woman with pincer nail deformity associated with systemic lupus
erythematosus. A renal biopsy confirmed class V lupus nephritis and treatment had
included systemic steroids and cyclophosphamide. After 6 months there was a
marked improvement of nail deformities.
PMID- 28420049
TI - The spectrum of neuropsychiatric lupus in a Black Caribbean population: a report
of the Barbados National Lupus Registry.
AB - Objective The objective of this study was to examine neuropsychiatric lupus in a
Black Caribbean population. Methods We reviewed Barbados National Lupus Registry
patients with >=4 American College of Rheumatology criteria and a diagnosis of
neuropsychiatric lupus using the American College of Rheumatology 19 case
definitions. Results From 366 patients with four or more American College of
Rheumatology criteria for systemic lupus erythematosus, 55 (15%) had evidence of
neuropsychiatric lupus. There were 51 females and four males (F:M = 13:1) with a
median age of 31 years. A total of 76.4% had a single neuropsychiatric lupus
complication and 23.6% had two or three complications occurring sequentially or
concurrently. The top three complications were psychosis - 49.1% (95% CI 35.8,
62.5); ischaemic stroke - 32.7% (21.4, 46.5); and generalized tonic-clonic
seizures - 12.7% (6.0, 24.8). Twelve of the American College of Rheumatology 19
neuropsychiatric syndromes were represented: 91.2% central; 8.8% peripheral.
There were 521 observation years, and for 32 patients (58%) neuropsychiatric
lupus was a presenting feature. For the remaining 23 (42%) the first
neuropsychiatric lupus event came after systemic lupus erythematosus diagnosis -
median time of two years. Of the 22 deaths, systemic lupus erythematosus
nephritis caused almost half (45.5%) at a median age of 32. The prevalence of
nephritis was lower in the neuropsychiatric lupus subgroup (25.5%) compared with
the Barbados National Lupus Registry data (47%) ( P = 0.01). Ischaemic stroke
caused 22.7% of deaths at a median age of 46 and was the main cause of chronic
neurologic deficits amongst survivors. Conclusion Neuropsychiatric lupus was an
early cause of morbidity in systemic lupus erythematosus with predominantly
singular central nervous system complications, the most common of which was
psychosis. Most deaths occurred at a young age, principally from systemic lupus
erythematosus nephritis. Ischaemic stroke was the main neurologic cause of death
and disability.
PMID- 28420050
TI - Carotid intima-media thickness and arterial stiffness in pediatric systemic lupus
erythematosus.
AB - Objectives The carotid intima-media thickness (CIMT) and carotid arterial
stiffness index (CASI) act as the surrogate markers of atherosclerosis. We aim to
assess CIMT and CASI in pediatric systemic lupus erythematosus (SLE). Methods
Patients <= 20 years old fulfilling diagnostic criteria for SLE were enrolled.
Patients with active smoking, coronary heart disease, cerebrovascular disease,
arterial thrombosis, family history of hypercholesterolemia, chronic liver
disease, or other chronic severe diseases were excluded. The patients were
categorized into four groups: active SLE, age- and sex-matched control (control
A), inactive SLE, and age- and sex-matched control (control I), according to the
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). All subjects
underwent ultrasound of carotid arteries to evaluate CIMT and CASI. Results One
hundred and two SLE patients (26 active and 76 inactive) and one hundred and
three healthy controls (26 control A and 77 control I) were enrolled. The median
CIMT in all groups were not significantly different (0.43, 0.41-0.44; 0.43, 0.41
0.44; 0.42, 0.41-0.43; and 0.42, 0.41-0.43 mm, respectively).The CASI in active
SLE (13.5, 11.4-17.3) was significantly higher than in control A (8.2, 7.2-9.2) (
p < 0.0001), whereas CASI in inactive SLE (12.7, 10.9-15.7) was significantly
higher than in control I (8.9, 7.6-9.8). However, the CASI in active and inactive
SLE was not significantly different. Conclusions The higher CASI in active and
inactive pediatric SLE, implying functional change of carotid arteries, may be
early evidence of increased atherosclerosis in pediatric SLE. This functional
dysfunction has been found both in inactive and active SLE.
PMID- 28420051
TI - Circulating prolactin level in systemic lupus erythematosus and its correlation
with disease activity: a meta-analysis.
AB - Objective This study aimed to evaluate the relationship between circulating
prolactin level and systemic lupus erythematosus (SLE), and to establish a
correlation between plasma/serum prolactin levels and SLE activity. Methods We
performed a meta-analysis comparing the plasma/serum prolactin levels in patients
with SLE to controls, and examined correlation coefficients between circulating
prolactin level and SLE disease activity. Results Twenty-five studies with a
total of 1056 SLE patients and 426 controls were included. Prolactin levels were
significantly higher overall in the SLE group than in the control group
(standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 * 10
5). Stratification by ethnicity showed significantly elevated prolactin levels in
the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95%
CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD =
1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European
population. Subgroup analysis by sample size showed significantly higher
prolactin levels in the SLE group by small ( n < 30) and large sample numbers ( n
> 30). Meta-analysis of correlation coefficients showed a significantly positive
correlation between circulating prolactin level and SLE activity (correlation
coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 * 10-9). Circulating prolactin
levels were positively associated with SLE activity in European, Asian, and mixed
populations (SMD = 0.532, 95% CI = 0.443-0.609 p < 1.0 * 10-8; SMD = 0.427, 95%
CI = 0.240-0.583, p = 2.4 * 10-5; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 * 10
5, respectively). Conclusions Our meta-analysis demonstrated that circulating
prolactin levels are higher in patients with SLE, and that a significantly
positive correlation exists between prolactin levels and SLE activity.
PMID- 28420052
TI - Lupus nephritis in the Western Cape, a high prevalence area: an experience over
three decades.
AB - Background Systemic lupus erythematosus is a multisystem disease with serious
complications, including lupus nephritis. Systemic lupus erythematosus is
prevalent in the Western Cape, predominantly affecting women in the prime of
their lives. Renal biopsy is an important tool for the management of the lupus
patient with kidney disease, guiding treatment and assessing prognosis. Aims The
aim of this study was to ascertain if there has been a change in the spectrum of
renal pathology, patient characteristics and long-term outcomes in patients with
lupus nephritis in our region over three decades. Methods We reviewed 315 records
of systemic lupus erythematosus patients with suspected renal disease who
underwent renal biopsy in the Renal Unit at Tygerberg Hospital over three decades
between January 1983 and December 2012. Results Lupus nephritis consistently
affected young women. Class IV lupus nephritis remained the most common pattern
throughout the three decades. The overall five-year survival for this cohort was
67% (95% confidence interval (CI), 60-72%). Conclusion Class IV lupus nephritis
remained the most frequent class in our cohort of patients with the poorest
survival rates compared to other classes. The prognosis of lupus nephritis in our
region is considerably worse than that reported elsewhere in the world.
PMID- 28420053
TI - Risk of infective endocarditis in patients with systemic lupus erythematosus in
Taiwan: a nationwide population-based study.
AB - Objectives Patients with systemic lupus erythematosus are considered vulnerable
to infective endocarditis and prophylactic antibiotics are recommended before an
invasive dental procedure. However, the evidence is insufficient. This nationwide
population-based study evaluated the risk and related factors of infective
endocarditis in systemic lupus erythematosus. Methods We identified 12,102
systemic lupus erythematosus patients from the National Health Insurance research
oriented database, and compared the incidence rate of infective endocarditis with
that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable
proportional hazards model was employed to evaluate the risk of infective
endocarditis in the systemic lupus erythematosus cohort. Results After a mean
follow-up of more than six years, the systemic lupus erythematosus cohort had a
significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per
100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the
control cohort. By contrast, the older systemic lupus erythematosus cohort had
lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years
systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox
multivariate proportional hazards analysis revealed heart disease (hazard ratio =
5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034),
receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001),
and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001)
were independent risk factors for infective endocarditis in systemic lupus
erythematosus patients. Conclusions A higher risk of infective endocarditis was
observed in systemic lupus erythematosus patients. Risk factors for infective
endocarditis in the systemic lupus erythematosus cohort included heart disease,
chronic kidney disease, steroid pulse therapy within 30 days, and a recent
invasive dental procedure within 30 days.
PMID- 28420054
TI - The prevalence and determinants of anti-DFS70 autoantibodies in an international
inception cohort of systemic lupus erythematosus patients.
AB - Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the
diagnosis of SLE when they occur in the absence of other SLE-related
autoantibodies. This study is the first to report the prevalence of anti-DFS70 in
an early, multinational inception SLE cohort and examine demographic, clinical,
and autoantibody associations. Patients were enrolled in the Systemic Lupus
International Collaborating Clinics (SLICC) inception cohort within 15 months of
diagnosis. The association between anti-DFS70 and multiple parameters in 1137
patients was assessed using univariate and multivariate logistic regression. The
frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6
1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with
musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti
beta2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients
with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI:
0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence
of anti-DFS70 was higher than the range previously published for adult SLE (7.1
versus 0-2.8%) and was associated with musculoskeletal activity and anti-beta2
glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies
were rare (1.1%) and therefore may be helpful to discriminate between ANA
positive healthy individuals and SLE.
PMID- 28420055
TI - Perceived stress and reported cognitive symptoms among Georgia patients with
systemic lupus erythematosus.
AB - Objective To examine associations of perceived stress with cognitive symptoms
among adults with systemic lupus erythematosus (SLE). Methods Among 777 adult
(>=18 years) SLE patients, the association of Perceived Stress Scale (PSS) scores
with two self-reported cognitive symptoms was examined: forgetfulness
(severe/moderate vs. mild/none; from the Systemic Lupus Activity Questionnaire)
and difficulty concentrating (all/most vs. some/little/none of the time; from the
Lupus Impact Tracker). The study used multivariable logistic regression to
estimate the odds ratios (ORs) per minimal important difference (MID = 0.5*SD) of
PSS score and cognitive symptoms. Results Forgetfulness and difficulty
concentrating were reported by 41.7% and 29.5%, respectively. Women and those
with less education and high disease activity had higher PSS scores and were more
likely to report cognitive symptoms than their counterparts. With adjustment for
age, race, sex, education, and disease activity, each MID increase in PSS score
was associated with higher prevalence of forgetfulness (OR = 1.43, 95% CI 1.29
1.47) and difficulty concentrating (OR = 2.19, 95% CI 1.90-2.52). No substantial
differences in this association by age, race, sex, or disease activity were
noted. Conclusions SLE patients, particularly those with high disease activity,
report a high burden of cognitive symptoms, for which stress may be a modifiable
risk factor.
PMID- 28420056
TI - Treatment with belimumab in systemic lupus erythematosus does not impair antibody
response to 13-valent pneumococcal conjugate vaccine.
AB - Background/purpose The objective of this study was to explore the impact of
systemic lupus erythematosus and belimumab given in addition to standard of care
therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods
Forty-seven systemic lupus erythematosus patients and 21 healthy controls were
immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty
systemic lupus erythematosus patients were treated with traditional disease
modifying anti rheumatic drugs, 11 of those received belimumab in addition, and
32 patients were treated with concomitant prednisolone. Quantification of
serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was
performed in serum taken before and four to six weeks after vaccination using
multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F
and 6B were also analyzed using standard enzyme-linked immunosorbent assays.
Opsonophagocytic assay was performed on serotype 23F to evaluate the
functionality of the antibodies. Pre- and post-vaccination log transformed
antibody levels were compared to determine the impact of systemic lupus
erythematosus diagnosis and different treatments on antibody response. Results
Systemic lupus erythematosus patients as a group showed lower post-vaccination
antibody levels and lower fold increase of antibody levels after vaccination
compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus
erythematosus patients treated with belimumab in addition to standard of care
therapy or with only hydroxychloroquine did not differ compared to controls,
whereas the other treatment groups had significantly lower fold increase of post
vaccination antibody levels. Higher age was associated with lower post
vaccination antibody levels among systemic lupus erythematosus patients.
Conclusion Belimumab given in addition to traditional disease-modifying anti
rheumatic drugs or prednisolone did not further impair antibody response to 13
valent conjugated pneumococcal vaccine.
PMID- 28420057
TI - Central nervous system vasculitis in systemic lupus erythematosus: a case series
report in a tertiary referral centre.
AB - Central nervous system (CNS) vasculitis (CNS) in systemic erythematosus lupus
(SLE) is a rare and challenging diagnosis. We report four cases of CNS vasculitis
that occurred 5 to 16 years after the diagnosis of SLE. Magnetic resonance
imaging (MRI) detected different features suggestive of CNS vasculitis:
enhancement and thickening of the vascular wall, vascular stenosis, ischemic
brain lesions and intracerebral haemorrhage unlikely to correspond to other mimic
aetiologies. Three patients received combination therapy with glucocorticoids
(GC) and cyclophosphamide (CYC). Intravenous human immunoglobulin (IVIG) was
administered when the patient had a past history of serious adverse event to CYC
or high infectious risk. All patients showed imagiological improvement, at least
partially, 5 to 23 days after starting treatment. We discuss the management of
CNS in SLE including the role of magnetic resonance imaging (MRI).
PMID- 28420058
TI - Clinico-pathological features of repeat renal biopsies in patients with lupus
nephritis at Groote Schuur Hospital, Cape Town.
AB - Background Repeat renal biopsies in patients with lupus nephritis are usually
done to guide treatment or to establish disease chronicity. Their value is not
clear from available literature. There are also no available data in Africa to
guide clinicians. Methods This was a retrospective study of patients undergoing a
repeat renal biopsy between January 2003 and December 2014 from a single centre
in Cape Town, South Africa. Relevant demographic, clinical and histological
records of patients with repeat renal biopsies were documented. Comparison of
data from first and second renal biopsy was performed. Results Forty-four
patients had at least two biopsies done during the study period. Most patients
were females (81.8%). The mean biopsy interval was 2.8 +/- 1.8 (range 0.38-9.4)
years. Proteinuria was the main indication for the repeat biopsy (36.1%). The
glomerular filtration rate and proteinuria worsened between the two biopsies ( p
= 0.001 and 0.019, respectively) suggesting disease progression. Most patients
(65.4%) with a non-proliferative class of lupus nephritis at first biopsy
progressed into a proliferative class, whereas patients with initial
proliferative lupus nephritis at first biopsy (77.8%) remained as proliferative
at repeat biopsy. Treatment was changed in 85% of patients at second biopsy.
Conclusion Repeat renal biopsies in patients with lupus nephritis presents a
useful means of assessing disease progression and provides guidance regarding
modification of treatment. More studies are, however, required to evaluate the
value of repeat biopsies and perhaps the need for protocol renal biopsies in
patients with lupus nephritis.
PMID- 28420059
TI - Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of
life.
AB - Objective Assess quality of life in patients with systemic lupus erythematosus
(SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE).
Methods Quality of life was assessed using the Short-Form 36 item Health Survey
(SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow
up. SF-36 subscales and summary scores were calculated and compared with quality
of life of the general Dutch population and patients with other chronic diseases.
Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98
had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom
64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a
significantly reduced quality of life in all subscales of the SF-36. Quality of
life at follow-up showed a significant improvement in physical functioning role (
p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health
( p = 0.014) and mental component score ( p = 0.042) in patients with
neuropsychiatric symptoms not attributed to SLE, but no significant improvement
was seen in patients with NPSLE. Conclusion Quality of life is significantly
reduced in patients with SLE presenting neuropsychiatric symptoms compared with
the general population and patients with other chronic diseases. Quality of life
remains considerably impaired at follow-up. Our results illustrate the need for
biopsychosocial care in patients with SLE and neuropsychiatric symptoms.
PMID- 28420060
TI - Risk factors to predict the development of chronic kidney disease in patients
with lupus nephritis.
AB - Objectives We analyzed the clinical follow-up results of 88 lupus nephritis
patients to find prognostic factors for the development of chronic kidney disease
in ethnically homogeneous Korean patients with biopsy-proven lupus nephritis.
Methods Sociodemographic, clinical, laboratory, and treatment-related data at the
time of kidney biopsy and during follow-up were obtained. Renal biopsy specimens
were reclassified according to the International Society of Pathology/Renal
Pathology Society classification, separately, by two renal pathologists blinded
to the previous classification. Univariate and multivariate analyses were
performed using the Cox proportional hazard regression model to identify
independent risk factors for chronic kidney disease in lupus nephritis patients.
Results Eighteen of 88 patients (20.5%) developed chronic kidney disease during a
mean follow-up of 47.6 months (range: 12-96 months). Patients who developed
chronic kidney disease were older at onset of lupus nephritis, had less
education, and were more likely to have hypertension; they had lower serum
albumin levels, lower platelet levels, higher serum creatinine levels, lower
estimated glomerular filtration rate, higher chronicity index, and lower
frequency of anti-ribosomal P antibodies, and they were less likely to be in
complete remission in the first year. In stepwise multivariable analyses,
hypertension, lower glomerular filtration rate, and failure to achieve complete
remission in the first year of treatment were significant predictors of the
development of chronic kidney disease in lupus nephritis patients. Conclusions
These findings suggest that patients with hypertension and decreased kidney
function at the onset of lupus nephritis and showing a poor response to
immunosuppressive drugs in the first year should be monitored carefully and
managed aggressively to avoid deterioration of kidney function.
PMID- 28420061
TI - Metabolic profiling reveals new serum biomarkers of lupus nephritis.
AB - Metabolomics has been applied to explore altered metabolite profiles in disease
and identify unique metabolic signatures specific to certain pathologies. The aim
of the current study is to characterize the metabolic profile of patients
diagnosed with lupus nephritis (LN) and explore new insights into underlying
disease processes. A metabolomic approach using ultra-high-performance liquid
chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) was
developed in serum samples from 32 LN patients, 30 idiopathic nephrotic syndrome
(INS) patients and 28 healthy controls (HCs). Potential biomarkers were screened
from orthogonal projection to latent structures discriminate analysis (OPLS-DA)
and further evaluated by receiver operating characteristic analysis (ROC). A
total of 14 potential biomarkers were screened and tentatively identified for LN
patients compared to HCs. Compared to HCs and INS patients, the LN patients had
increased serum levels of sorbitol and glycocholic acid metabolites and decreased
levels of cortisol, creatinine and L-aspartyl-L-phenylalanine. A panel of three
metabolomics (theophylline, oxidized glutathione and capric acid) was identified
as biomarkers of LN with a sensitivity of 87.50% and a specificity of 67.86%
using ROC analysis. Our results suggest that UPLC-HRMS based quantification of
circulating metabolites was a useful tool for identification of biomarkers with
the ability to segregate LN patients from INS patients and HCs. The potential
biomarkers indicated that the LN metabolic disturbance may be closely associated
with inflammation injury, oxidative stress and phospholipid metabolism.
PMID- 28420062
TI - Intravenous immunoglobulin: a biological corticosteroid-sparing agent in some
autoimmune conditions.
AB - Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of
autoimmune and systemic inflammatory diseases. This compound is effective in a
wide range of clinical conditions other than primary immunodeficiency, including
autoimmune diseases, inflammatory disorders, infections, organ transplantation,
and possibly supportive therapy for cancer. Systemic corticosteroids remain the
gold standard treatment for many autoimmune diseases, but their long-term use is
associated with complications in diverse organs and systems. Osteoporosis,
osteonecrosis, cardiovascular disease, infections, and cancer have been
associated with this treatment. Therefore, physicians are occasionally forced to
withdraw the treatment with steroids. Biological agents may represent a good
alternative, but in addition to being very expensive, these agents may have
serious side effects. This review aimed to cover the major advances in the use of
IVIg as a steroid-sparing agent in some relevant autoimmune diseases.
PMID- 28420063
TI - Patients' experiences of lupus-related foot problems: a qualitative
investigation.
AB - Background Systemic lupus erythematosus (SLE) can present with a variety of
symptoms. Previous research has shown there is a high prevalence of lower limb
and foot problems in patients with SLE associated with the musculoskeletal,
vascular and neurological changes. Furthermore, there is a high prevalence of
infections affecting the feet and a range of common skin and nail problems.
However, it is not known how these foot problems impact upon people's lives.
Therefore, we aimed to explore this using a qualitative approach. Method
Following ethical approval, 12 participants were recruited who had a diagnosis of
SLE, current and/or past experience of foot problems and were over 18 years in
age. Following consent, interviews were carried out with an interpretivist
phenomenological approach to both data collection and analysis. Results Seven
themes provide insight into: foot problems and symptoms; the impact of these foot
problems and symptoms on activities; disclosure and diagnosis of foot problems;
treatment of foot problems and symptoms; perceived barriers to professional
footcare; unanswered questions about feet and footcare; and identification of the
need for professional footcare and footcare advice. Conclusion These participants
tend to "self-treat" rather than disclose that they may need professional
footcare. A lack of focus upon foot health within a medical consultation is
attributed to the participant's belief that it is not within the doctor's role,
even though it is noted to contribute to reduced daily activity. There is a need
for feet to be included as a part of patient monitoring and for foot health
management to be made accessible for people with SLE.
PMID- 28420064
TI - Anti-topoisomerase-I antibodies in systemic lupus erythematosus and potential
association with the presence of anti-dsDNA antibodies.
PMID- 28420065
TI - A five consecutive years' study of renal function outcome among biopsy proven
lupus nephritis patients in Southern Iran.
AB - Introduction Lupus nephritis (LN) is one of the most common complications of
systemic lupus erythematous (SLE) responsible for an increase in mortality and
morbidity. This study was conducted to evaluate the outcome for LN patients and
factors that correlate with their outcome. Materials and methods We included 80
patients with proved LN and more than three-years follow up at Shiraz University
of Medical Sciences. We prepared a data gathering sheet for each patient and
extracted the data from patients' file records which existed in the hospital.
Results The mean age of patients was 36.6 +/- 10.6 years, and 88.3% of patients
were women. Men develop remission less than women (three men (33.3%) vs 49 women
(72.1%), p = 0.014). Chronic kidney disease (GFR < 60) developed in 14.2% of our
patients, and 7.8% progressed to end stage renal disease (ESRD). We found a
significant relation between initial creatinine (Cr), GFR, and urine 24 hour
protein with developing ESRD ( p = 0.002, 0.039, < 0.001, respectively). Also we
found that hypertensive patients are at risk of developing ESRD 0.4 times more
than normotensive patients ( p = 0.047, CI: 0.131-0.985). Lack of remission was
significantly associated with ESRD progression ( p = 0.025). Conclusion There is
a strong agreement among studies that initial Cr, hypertension and lack of
remission are associated with poor outcome in LN patients. As a result we must
observe hypertensive patients and patients with increased Cr more carefully.
Also, we should consider changing treatment in patients who do not develop
remission. In spite of dominancy of women in SLE, men are likely to have poorer
outcomes.
PMID- 28420066
TI - Disease evolution in late-onset and early-onset systemic lupus erythematosus.
AB - Objective The objective of this study was to compare clinical features, disease
activity, and outcome in late-onset versus early-onset systemic lupus
erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970
were followed prospectively according to standard protocol and tracked on a
computerized database. Patients entering the cohort within one year of diagnosis
constitute the inception cohort. Patients with late-onset (age at diagnosis >=50)
disease were identified and matched 1:2 based on gender and first clinic visit
(+/-5) years with patients with early-onset disease (age at diagnosis 18-40
years). Results A total of 86 patients with late-onset disease (84.9% female,
81.4% Caucasian, mean age at SLE diagnosis +/- SD 58.05 +/- 7.30) and 169
patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE
diagnosis +/- SD 27.80 +/- 5.90) were identified. At enrollment, late-onset SLE
patients had a lower total number of American College of Rheumatology (ACR)
criteria, with less renal and neurologic manifestations. Mean SLE Disease
Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially
renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores
decreased in both groups, while mean Systemic Lupus International Collaborating
Clinics/ACR Damage Index (SDI) scores increased more significantly in the late
onset group; they developed more cardiovascular, renal, and ocular damage, and
had higher prevalence of cardiovascular risk factors. Conclusion Although the
late-onset SLE group had a milder presentation and less active disease, with the
evolution of disease, they developed more organ damage likely as a consequence of
cardiovascular risk factors and aging.
PMID- 28420067
TI - Kidney transplantation for end-stage renal disease in lupus nephritis, a very
safe procedure: a single Latin American transplant center experience.
AB - Background Lupus nephritis (LN) is one of the most frequent complications of SLE
and occurs in up to 50% of cases depending on the studied population. Of these,
approximately 20% progress to end-stage renal disease (ESRD), with the treatment
of choice being a kidney transplant. Objective The objective of this study was to
describe the clinical outcome of patients transplanted due to LN, compared with
patients transplanted for other causes, in a Latin American population from the
Fundacion Valle del Lili in Cali, Colombia. Methods Observational, retrospective
case study with controls matched by age, sex and type of donor in a single center
between 1996 and 2014. Results Sixty-five kidney transplants were performed in
patients with LN and ESRD. The survival of patients with LN was 98% at 1, 10 and
15 years ( p = .99). For controls by age and sex, survival was also 98% at 15
years post-transplant, and for controls by donor, the survival rate was 100% at 5
years and 98% at 15 years. Graft survival in patients with LN to 1, 5 and 15
years was 92%, 83% and 71%, respectively; for controls by age and sex, it was
90%, 84% and 64%, respectively, and for the controls by donor, it was 89%, 86%
and 79%, respectively ( p = .7718). There were no statistically significant
differences found in the cumulative incidence of acute graft rejection in the
first year, but it was found that acute rejection is a factor that relates to the
loss of function of the renal graft ( p = .032). Of the patients transplanted for
LN, two (3.1%) experienced a recurrence of the disease. One patient died after a
diagnosis of recurrence of LN due to an infection. Conclusions Kidney
transplantation is a good option for patients with ESRD due to LN. In this
Hispanic population, the survival of patients, graft survival, and cumulative
incidence of graft rejection are not different from those of other transplanted
patients. In addition, recurrence of LN was rare, showing the benefits of renal
transplantation in LN patients with ESRD.
PMID- 28420068
TI - Pentraxin-3 levels are associated with vasculitis and disease activity in
childhood-onset systemic lupus erythematosus.
AB - Objectives Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic
autoimmune disease characterized by inflammatory organ damage by means of
vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory
processes, predominantly from endothelial cells. In adult studies, PTX3 has shown
to be an indicator of active vasculitis both in large-vessel and small-vessel
vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated
with disease activity, and with some of the clinical manifestations and
laboratory parameters. We aimed to ascertain if PTX3 might be a significant
mediator in cSLE and if it might indicate active vasculitis during the course of
the disease. Methods Serum PTX3 levels were measured in 76 patients with cSLE and
41 healthy subjects. We have investigated its relation with disease activity,
damage, clinical features, laboratory parameters and medications. Results Serum
levels of PTX3 were found to be increased in cSLE compared to healthy controls
(mean +/- SD; 10.6 +/- 8.2 ng/mL vs 2.7 +/- 1.3 ng/mL, p < 0.001). PTX3
concentrations were also in correlation with SLEDAI-2K ( r = 0.57, p < 0.001).
When viewed from the clinical perspective, serum PTX3 levels were significantly
higher only in patients with active vasculitis ( p < 0.001), Raynaud phenomenon (
p = 0.006) and mucocutaneous manifestations ( p < 0.001). However, an association
between PTX3 and age, age at disease onset, disease duration, complement levels,
PedSDI score (pediatric version of the Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin
levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected.
Conclusions Patients with cSLE have increased levels of serum PTX3 compared to
healthy controls. Thus, serum PTX-3 level might be a significant mediator in
cSLE. Apart from these, the results support that PTX3 reflects active cutaneous
vasculitis in cSLE and correlates with disease activity.
PMID- 28420069
TI - Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance
and disease activity in systemic lupus erythematosus: a cross-sectional human
study.
AB - Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has
recently been involved in the pathogenesis of autoimmune diseases. To assess
whether LL-37 reflects disease activity, we measured serum levels of it in
systemic lupus erythematosus (SLE) patients with active and inactive disease
compared to healthy controls. LL-37 was also compared between new and old cases.
Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was
measured. Methods The study population consisted of 50 SLE patients and 28
healthy controls. Of those, 39 patients had active and 11 patients had inactive
disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special
method. Results There was no difference in levels of LL-37 between patients and
healthy controls (50.9 +/- 20.8 vs. 67.7 +/- 43.3 ng/ml, P = 0.31). LL-37 did not
correlate with SLEDAI and its items in total patients. LL-37 had a positive
correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active
patients (78% of patients), multivariate regression analysis showed significant
negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50).
No difference was found in levels of PAB between patients and controls (90.4 +/-
34.1 vs. 86.9 +/- 25.6 HK, P = 0.4).There was no difference in the levels of PAB
between patients with active and inactive disease (93.2 +/- 34.1 vs. 80.2 +/-
33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI
items and total score. However, a positive correlation between the levels of LL
37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on
this study, serum LL-37 and PAB did not increase in lupus compared with healthy
individuals. LL-37 serum values rose in parallel with SLEDAI in active disease.
Positive correlation between serum PAB and LL-37 could be a great achievement of
this study that may suggest the role of antioxidants in controlling NETosis.
PMID- 28420070
TI - Lower kidney allograft survival in African-Americans compared to Hispanic
Americans with lupus.
AB - Background and objective African-Americans and Hispanic-Americans with lupus are
the two most common minority groups who receive kidney transplants in the USA. It
is unknown if African-Americans and Hispanic-Americans with lupus have similar
outcomes after kidney transplantation. In this study, we assessed whether African
Americans compared to Hispanic-Americans have worse kidney allograft survival
after risk factors of rejection and other prognostic factors were matched between
both groups. Methods Out of 1816 African-Americans and 901 Hispanic-Americans
with lupus, who received kidney transplants between 1987 and 2006 and had
complete records in the UNOS program, 478 pairs were matched in 16 baseline
predictors and follow-up time employing a predicted probability of group
membership. The primary outcome was kidney allograft survival. Main secondary
outcomes were rejection, allograft failure attributed to rejection, and
mortality. Results Matched pairs were predominantly women (81%) with the mean age
of 36 years. 96% were on dialysis before transplantation. 89% of recipients
received kidneys from deceased donors and 15.5% from expanded criteria donors.
12% of recipients had zero HLA mismatch. African-Americans compared to Hispanic
Americans had lower cumulative allograft survival during 12-year follow-up ( p <
0.001). African-Americans compared to Hispanic-Americans had higher rates of
rejection (10.4 vs 6.73 events/100 patients-years; p = 0.0002) and allograft
failure attributed to rejection (6.31 vs 3.99; p = 0.0023). However, African
Americans and Hispanic-Americans had similar mortality rates (2.71 vs 2.31; p =
0.4269). Conclusions African-Americans compared to Hispanic-Americans with lupus
had lower kidney allograft survival when recognized risk factors of rejection
were matched between groups.
PMID- 28420071
TI - Pleuropulmonary involvement in patients with systemic lupus erythematosus from a
Latin American inception cohort (GLADEL).
AB - Objectives The objectives of this study were to examine the demographic and
clinical features associated with the occurrence of pleuropulmonary
manifestations, the predictive factors of their occurrence and their impact on
mortality in systemic lupus erythematosus (SLE) patients. Materials and methods
The association of pleuropulmonary manifestations with demographic and clinical
features, the predictive factors of their occurrence and their impact on
mortality were examined in GLADEL patients by appropriate univariable and
multivariable analyses. Results At least one pleuropulmonary manifestation
occurred in 421 of the 1480 SLE patients (28.4%), pleurisy being the most
frequent (24.0%). Age at SLE onset >=30 years (OR 1.42; 95% CI 1.10-1.83), the
presence of lower respiratory tract infection (OR 3.19; 95% CI 2.05-4.96), non
ischemic heart disease (OR 3.17; 95% CI 2.41-4.18), ischemic heart disease (OR
3.39; 95% CI 2.08-5.54), systemic (OR 2.00; 95% CI 1.37-2.91), ocular (OR 1.58;
95% CI 1.16-2.14) and renal manifestations (OR 1.44; 95% CI 1.09-1.83) were
associated with pleuropulmonary manifestations, whereas cutaneous manifestations
were negatively associated (OR 0.47; 95% CI 0.29-0.76). Non-ischemic heart
disease (HR 2.24; 95% CI 1.63-3.09), SDI scores >=1 (OR 1.54; 95% CI 1.10-2.17)
and anti-La antibody positivity (OR 2.51; 95% CI 1.39-4.57) independently
predicted their subsequent occurrence. Cutaneous manifestations were protective
of the subsequent occurrence of pleuropulmonary manifestations (HR 0.62; 95% CI
0.43-0.90). Pleuropulmonary manifestations independently contributed a decreased
survival (HR: 2.79 95% CI 1.80-4.31). Conclusion Pleuropulmonary manifestations
are frequent in SLE, particularly pleuritis. Older age, respiratory tract
infection, cardiac, systemic and renal involvement were associated with them,
whereas cutaneous manifestations were negatively associated. Cardiac compromise,
SDI scores >=1 and anti-La positivity at disease onset were predictive of their
subsequent occurrence, whereas cutaneous manifestations were protective. They
independently contributed to a decreased survival in these patients.
PMID- 28420072
TI - Reduction of nitric oxide and DNA/RNA oxidation products are associated with
active disease in systemic lupus erythematosus patients.
AB - The aims of the present study were to evaluate biomarkers of oxidative and
nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular
products of DNA/RNA oxidative damage and their correlation with disease activity.
This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI
< 6) and 50 with active SLE (SLEDAI >= 6) without renal impairment. Oxidative
stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence,
advanced oxidation protein products (AOPP), total radical-trapping antioxidant
parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products.
Patients with SLE showed increased oxidative stress, as demonstrated by the
augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and
reduced total antioxidant capacity ( p < 0.0001), without differences between
patients with active disease and in remission. NOx levels and DNA/RNA oxidation
products were inversely and independently associated with disease activity ( p <
0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The
linear regression analysis showed that about 5% of the SLEDAI score can be
explained by the levels of DNA/RNA oxidation products ( r2:0.051; p = 0.002) and
about 9% of this score by the levels of NOx ( r2:0.091; p < 0.0001). This study
provides evidence for an inverse association between serum NOx levels and DNA/RNA
oxidation products and SLE disease activity, suggesting that
oxidative/nitrosative stress markers may be useful in evaluating SLE disease
activity and progression of the disease.
PMID- 28420073
TI - Future Prospects for the Development of Cost-Effective Adenovirus Vaccines.
AB - Vaccination is one of the most efficient tools for disease prevention, and a
continuously growing field of research. However, despite progress, we still need
more efficient and cost-effective vaccines that would improve access to those in
need. In this review, we will describe the status of virus-vectored vaccine
technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines
have proven to be efficient in military vaccinations against Ad4 and Ad7 and as
highly efficient vectored vaccines against rabies. The question of how other
adenovirus-based vaccines can become as efficient as the rabies vaccine is the
underlying theme in this review. Here, we will first give an overview of the
basic properties of vectored vaccines, followed by an introduction to the
characteristics of adenoviral vectors and previously tested modifications of the
vector backbone and expression cassettes, with a focus on how they can contribute
to increased vaccine cost-effectiveness. Finally, we will highlight a few
successful examples of research that have attempted to improve the use of
adenoviral-based vaccines by improving the transgene immunogenicity.
PMID- 28420074
TI - Natural Pathogen Control Chemistry to Replace Toxic Treatment of Microbes and
Biofilm in Cooling Towers.
AB - Application of toxic antibacterial agents is considered necessary to control
prevalent fresh water microorganisms that grow in evaporative cooling water
systems, but can adversely affect the environment and human health. However,
natural antibacterial water chemistry has been applied in industrial cooling
water systems for over 10 years to inhibit microorganisms with excellent results.
The water chemistry method concentrates natural minerals in highly-softened water
to produce elevated pH and dissolved solids, while maintaining low calcium and
magnesium content. The method provides further benefits in water conservation,
and generates a small volume of non-toxic natural salt concentrate for cost
efficient separation and disposal if required. This report describes the
antimicrobial effects of these chemistry modifications in the cooling water
environment and the resultant collective inhibition of microbes, biofilm, and
pathogen growth. This article also presents a novel perspective of parasitic
microbiome functional relationships, including "Trojan Protozoans" and biofilms,
and the function of polyvalent metal ions in the formation and inhibition of
biofilms. Reducing global dependence on toxic antibacterial agents discharged to
the environment is an emerging concern due to their impact on the natural
microbiome, plants, animals and humans. Concurrently, scientists have concluded
that discharge of antibacterial agents plays a key role in development of
pathogen resistance to antimicrobials as well as antibiotics. Use of natural
antibacterial chemistry can play a key role in managing the cooling water
environment in a more ecologically sustainable manner.
PMID- 28420075
TI - Application of Hydrogen Peroxide as an Innovative Method of Treatment for
Legionella Control in a Hospital Water Network.
AB - OBJECTIVES: To evaluate the effectiveness of hydrogen peroxide (HP) use as a
disinfectant in the hospital water network for the control of Legionella spp.
colonization. METHODS: Following the detection of high levels of Legionella
contamination in a 136-bed general hospital water network, an HP treatment of the
hot water supply (25 mg/L) was adopted. During a period of 34 months, the
effectiveness of HP on Legionella colonization was assessed. Legionella was
isolated in accordance with ISO-11731 and identification was carried out by
sequencing of the mip gene. RESULTS: Before HP treatment, L. pneumophila sg 2-15
was isolated in all sites with a mean count of 9950 +/- 8279 cfu/L. After one
month of HP treatment, we observed the disappearance of L. pneumophila 2-15,
however other Legionella species previously not seen were found;
Legionellapneumophila 1 was isolated in one out of four sampling sites (2000
cfu/L) and other non-pneumophila species were present in all sites (mean load
3000 +/- 2887 cfu/L). Starting from September 2013, HP treatment was modified by
adding food-grade polyphosphates, and in the following months, we observed a
progressive reduction of the mean load of all species (p < 0.05), resulting in
substantial disappearance of Legionella colonization. CONCLUSION: Hydrogen
peroxide demonstrated good efficacy in controlling Legionella. Although in the
initial phases of treatment it appeared unable to eliminate all Legionella
species, by maintaining HP levels at 25 mg/L and adding food-grade
polyphosphates, a progressive and complete control of colonization was obtained.
PMID- 28420076
TI - Mitochondrial Genomes Provide Insights into the Phylogeny of Lauxanioidea
(Diptera: Cyclorrhapha).
AB - The superfamily Lauxanioidea is a significant dipteran clade including over 2500
known species in three families: Lauxaniidae, Celyphidae and Chamaemyiidae. We
sequenced the first five (three complete and two partial) lauxanioid
mitochondrial (mt) genomes, and used them to reconstruct the phylogeny of this
group. The lauxanioid mt genomes are typical of the Diptera, containing all 37
genes usually present in bilaterian animals. A total of three conserved
intergenic sequences have been reported across the Cyclorrhapha. The inferred
secondary structure of 22 tRNAs suggested five substitution patterns among the
Cyclorrhapha. The control region in the Lauxanioidea has apparently evolved very
fast, but four conserved structural elements were detected in all three complete
mt genome sequences. Phylogenetic relationships based on the mt genome data were
inferred by Maximum Likelihood and Bayesian methods. The traditional
relationships between families within the Lauxanioidea, (Chamaemyiidae +
(Lauxaniidae + Celyphidae)), were corroborated; however, the higher-level
relationships between cyclorrhaphan superfamilies are mostly poorly supported.
PMID- 28420077
TI - Recognition of the Duration and Prediction of Insect Prevalence of Stored Rough
Rice Infested by the Red Flour Beetle (Tribolium castaneum Herbst) Using an
Electronic Nose.
AB - The purpose of this research is to explore the feasibility of applying an
electronic nose for the intelligent monitoring of injurious insects in a stored
grain environment. In this study, we employed an electronic nose to sample rough
rice that contained three degrees of red flour beetle (Tribolium castaneum
Herbst) infestation for different durations-light degree (LD), middle degree
(MD), and heavy degree (HD)-and manually investigated the insect situation at the
same time. Manual insect situation investigation shows that, in all three rice
treatments, the insect amounts gradually decreased after infestation. When the
insect population of stored rough rice was under 13 insects per 60 g of rough
rice, the natural speed of decrease of the insect population became very slow and
reached the best artificial insect killing period. Linear discriminant analysis
(LDA) provided good performance for MD and HD insect harm duration
identification, but performed poorly for LD insect harm duration identification.
Both k-means clustering analysis (K-means) and fuzzy c-means analysis (FCM)
effectively identified the insect harm duration for stored rough rice. The
results from the back-propagation artificial neural network (BPNN) insect
prevalence prediction for the three degrees of rough rice infestation
demonstrated that the electronic nose could effectively predict insect prevalence
in stored grain (fitting coefficients were larger than 0.89). The predictive
ability was best for LD, second best for MD, and least accurate for HD. This
experiment demonstrates the feasibility of electronic noses for detecting both
the duration and prevalence of an insect infestation in stored grain and provides
a reference for the intelligent monitoring of an insect infestation in stored
grains.
PMID- 28420078
TI - Natural Phenol Polymers: Recent Advances in Food and Health Applications.
AB - Natural phenol polymers are widely represented in nature and include a variety of
classes including tannins and lignins as the most prominent. Largely consumed
foods are rich sources of phenol polymers, notably black foods traditionally used
in East Asia, but other non-edible, easily accessible sources, e.g., seaweeds and
wood, have been considered with increasing interest together with waste materials
from agro-based industries, primarily grape pomace and other byproducts of fruit
and coffee processing. Not in all cases were the main structural components of
these materials identified because of their highly heterogeneous nature. The
great beneficial effects of natural phenol-based polymers on human health and
their potential in improving the quality of food were largely explored, and this
review critically addresses the most interesting and innovative reports in the
field of nutrition and biomedicine that have appeared in the last five years.
Several in vivo human and animal trials supported the proposed use of these
materials as food supplements and for amelioration of the health and production
of livestock. Biocompatible and stable functional polymers prepared by peroxidase
catalyzed polymerization of natural phenols, as well as natural phenol polymers
were exploited as conventional and green plastic additives in smart packaging and
food-spoilage prevention applications. The potential of natural phenol polymers
in regenerative biomedicine as additives of biomaterials to promote growth and
differentiation of osteoblasts is also discussed.
PMID- 28420079
TI - How Hyperarousal and Sleep Reactivity Are Represented in Different Adult Age
Groups: Results from a Large Cohort Study on Insomnia.
AB - Hyperarousal is a 24-h state of elevated cognitive and physiological activation,
and is a core feature of insomnia. The extent to which sleep quality is affected
by stressful events-so-called sleep reactivity-is a vulnerability factor for
developing insomnia. Given the increasing prevalence of insomnia with age, we
aimed to investigate how hyperarousal and sleep reactivity were related to
insomnia severity in different adult age groups. Data were derived from a large
cohort study investigating the natural history of insomnia in a population-based
sample (n = 1693). Baseline data of the Arousal Predisposition Scale (APS) and
Ford Insomnia Response to Stress Test (FIRST) were examined across age and
sleep/insomnia subgroups: 25-35 (n = 448), 35-45 (n = 528), and 45-55 year olds
(n = 717); good sleepers (n = 931), individuals with insomnia symptoms (n = 450),
and individuals with an insomnia syndrome (n = 312). Results from factorial
analyses of variance (ANOVA) showed that APS scores decreased with increasing
age, but increased with more severe sleep problems. FIRST scores were not
significantly different across age groups, but showed the same strong increase as
a function of sleep problem severity. The findings indicate that though arousal
predisposition and sleep reactivity increase with more severe sleep problems,
only arousal decreases with age. How arousing events affect an individual during
daytime thus decreases with age, but how this arousal disrupts sleep is
equivalent across different adult age groups. The main implication of these
findings is that treatment of insomnia could be adapted for different age groups
and take into consideration vulnerability factors such as hyperarousal and stress
reactivity.
PMID- 28420080
TI - Delineating the Common Biological Pathways Perturbed by ASD's Genetic Etiology:
Lessons from Network-Based Studies.
AB - In recent decades it has become clear that Autism Spectrum Disorder (ASD)
possesses a diverse and heterogeneous genetic etiology. Aberrations in hundreds
of genes have been associated with ASD so far, which include both rare and common
variations. While one may expect that these genes converge on specific common
molecular pathways, which drive the development of the core ASD characteristics,
the task of elucidating these common molecular pathways has been proven to be
challenging. Several studies have combined genetic analysis with bioinformatical
techniques to uncover molecular mechanisms that are specifically targeted by
autism-associated genetic aberrations. Recently, several analysis have suggested
that particular signaling mechanisms, including the Wnt and Ca2+/Calmodulin
signaling pathways are often targeted by autism-associated mutations. In this
review, we discuss several studies that determine specific molecular pathways
affected by autism-associated mutations, and then discuss more in-depth into the
biological roles of a few of these pathways, and how they may be involved in the
development of ASD. Considering that these pathways may be targeted by specific
pharmacological intervention, they may prove to be important therapeutic targets
for the treatment of ASD.
PMID- 28420081
TI - Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and
Response to Tumor Necrosis Factor (TNF) Inhibitors.
AB - The term spondyloarthritis (SpA) is used to describe a group of multifactorial
chronic inflammatory diseases characterized by a predisposing genetic background
and clinical manifestations typically involving the sacroiliac joint. The absence
of pathognomonic clinical and/or laboratory findings generally results in a delay
in diagnosis and, consequently, in treatment. In addition, 20-40% of SpA patients
are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given
these considerations, it is important to identify biomarkers that can facilitate
the diagnosis and assessment of disease activity. As inflammation plays a key
role in the pathogenesis of SpA, inflammatory mediators have been investigated as
potential biomarkers for diagnosing the disease and predicting response to
therapy. Some investigators have focused their attention on the role of matrix
metalloproteinases (MMPs), which are known to be markers of synovial inflammation
that is generated in the joint in reaction to inflammatory stimuli. Several
studies have been carried out to verify if serum MMPs levels could be useful to
diagnose SpA, to assess disease severity, and to predict response to TNF
inhibitor therapy. The current review focuses on MMPs' role in SpA pathogenesis,
diagnosis and therapeutic implications.
PMID- 28420082
TI - Can Early Rehabilitation Prevent Posttraumatic Osteoarthritis in the
Patellofemoral Joint after Anterior Cruciate Ligament Rupture? Understanding the
Pathological Features.
AB - Knee instability resulting from anterior cruciate ligament (ACL) rupture is a
high-risk factor for posttraumatic osteoarthritis (PTOA) in the patellofemoral
joint (PFJ). However, whether non-weight-bearing and weight-bearing treatments
have chondroprotective effects remains unclear. Twenty-four adult New Zealand
White male rabbits were employed in this study. All animals received ACL
transection in the right knee and sham surgery in the left knee. The rabbits were
randomly assigned to the following groups: (I) In the sedentary (SED) group, the
rabbits (n = 6) were simply kept in their cage; (II) In the continuous passive
motion (CPM) group, the rabbits (n = 6) performed CPM exercise for 7 days,
starting from the first postoperative day; (III) In the active treadmill exercise
(TRE) group, the rabbits (n = 6) performed TRE for 2 weeks; (IV) In the CPM + TRE
group, the rabbits (n = 6) executed CPM exercise, followed by TRE. Two joint
surfaces (the retropatella and femoral trochlear groove) were assessed at 4 weeks
after operation. Although the gross appearance in each group was comparable,
histological examination revealed significant differences in the articular
cartilage status. The CPM group exhibited a greater thickness of articular
cartilage, maintenance of tidemark continuity, abundant glycosaminoglycan (GAG),
and significantly lower inflammatory cytokine 9, e.g., tumor necrosis factor
alpha (TNF-alpha) 0 levels, with modest cell apoptosis (i.e., caspase-3). By
contrast, the TRE group displayed the worst pathological features: an irregular
cartilage surface and chondrocyte disorganization, reduced cartilage thickness,
breakdown of the tidemark, depletion of collagen fibers, loss of GAG, and the
highest levels of TNF-alpha and caspase-3 expression. Furthermore, the CPM + TRE
group had more favorable outcomes than the SED group, indicating that suitable
exercise is needed. The sham treatment displayed no variance in the changes in
the two joint surfaces among groups. These data indicate that the application of
early CPM rehabilitation is suggested for subjects in order to decrease the risk
of PTOA without ACL reconstruction in the PFJ compartment in rabbits. The early
TRE program, however, had harmful outcomes. Additionally, inactivity was
discovered to initiate the development of PTOA.
PMID- 28420083
TI - A Theoretical Study and Numerical Simulation of a Quasi-Distributed Sensor Based
on the Low-Finesse Fabry-Perot Interferometer: Frequency-Division Multiplexing.
AB - The application of the sensor optical fibers in the areas of scientific
instrumentation and industrial instrumentation is very attractive due to its
numerous advantages. In the industry of civil engineering for example, quasi
distributed sensors made with optical fiber are used for reliable strain and
temperature measurements. Here, a quasi-distributed sensor in the frequency
domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot
interferometers where each Fabry-Perot interferometer acts as a local sensor.
Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg
gratings imprinted in a single mode fiber. All interferometer sensors have
different cavity length, provoking frequency-domain multiplexing. The optical
signal represents the superposition of all interference patterns which can be
decomposed using the Fourier transform. The frequency spectrum was analyzed and
sensor's properties were defined. Following that, a quasi-distributed sensor was
numerically simulated. Our sensor simulation considers sensor properties, signal
processing, noise system, and instrumentation. The numerical results show the
behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry
Perot sensor has high resolution and low resolution. Both resolutions are
conceivable because the Fourier Domain Phase Analysis (FDPA) algorithm elaborates
two evaluations of Bragg wavelength shift.
PMID- 28420084
TI - Assessment of the Occupational Health and Food Safety Risks Associated with the
Traditional Slaughter and Consumption of Goats in Gauteng, South Africa.
AB - BACKGROUND: This study assessed the occupational health and food safety risks
associated with the traditional slaughter of goats and the consumption of such
meat in Tshwane, South Africa. METHODS: A convenience sample of 105 respondents
agreed to be interviewed using structured questionnaires. RESULTS: A high
proportion (62.64%) of practitioners admitted to not wearing protective clothing
during slaughter. Slaughtering was mainly carried out by males (99%) with
experience (62.2%). Forty-four percent of practitioners only changed the clothes
they wore while slaughtering when they got home. During the actual slaughter, up
to seven people may be involved. The majority (58.9%) of slaughters occurred
early in the morning and none of the goats were stunned first. In 77.5% of cases,
the health status of the persons who performed the slaughtering was not known.
The majority (57.3%) of the slaughters were performed on a corrugated iron roof
sheet (zinc plate). In 83.3% of the cases, the carcass was hung up to facilitate
bleeding, flaying, and evisceration. Meat inspection was not practiced by any of
the respondents. Throughout the slaughter process, the majority used the same
knife (84.3) and 84.7% only cleaned the knife when it became soiled. A total of
52.0% of the respondents processed the carcass and cooked the meat immediately.
The majority (80.0%) consumed the meat within 30 min of cooking. CONCLUSIONS: Men
are at a higher risk of occupational health hazards associated with traditional
slaughter, which can be transferred to their households. Unhygienic methods of
processing and the lack of any form of post-mortem examination increase the risk
of food-borne illness following the consumption of such meat.
PMID- 28420085
TI - Electrochemical Detection of Dopamine Using 3D Porous Graphene Oxide/Gold
Nanoparticle Composites.
AB - The detection of dopamine in a highly sensitive and selective manner is crucial
for the early diagnosis of a number of neurological diseases/disorders. Here, a
report on a new platform for the electrochemical detection of dopamine with a
considerable accuracy that comprises a 3D porous graphene oxide (pGO)/gold
nanoparticle (GNP)/pGO composite-modified indium tin oxide (ITO) is presented.
The pGO was first synthesized and purified by ultrasonication and centrifugation,
and it was then further functionalized on the surface of a GNP-immobilized ITO
electrode. Remarkably, owing to the synergistic effects of the pGO and GNPs, the
3D pGO-GNP-pGO-modified ITO electrode showed a superior dopamine-detection
performance compared with the other pGO- or GNP-modified ITO electrodes. The
linear range of the newly developed sensing platform is from 0.1 MUM to 30 MUM
with a limit of detection (LOD) of 1.28 MUM, which is more precise than the other
previously reported GO-functionalized electrodes. Moreover, the 3D pGO-GNP-pGO
modified ITO electrodes maintained their detection capability even in the
presence of several interfering molecules (e.g., ascorbic acid, glucose). The
proposed platform of the 3D pGO-GNP-pGO-modified ITO electrode could therefore
serve as a competent candidate for the development of a dopamine-sensing platform
that is potentially applicable for the early diagnosis of various neurological
diseases/disorders.
PMID- 28420086
TI - Blockwise PPG Enhancement Based on Time-Variant Zero-Phase Harmonic Notch
Filtering.
AB - So far, many approaches have been developed for motion artifact (MA) reduction
from photoplethysmogram (PPG). Specifically, single-input MA reduction methods
are useful to apply wearable and mobile healthcare systems because of their low
hardware costs and simplicity. However, most of them are insufficiently developed
to be used in real-world situations, and they suffer from a phase distortion
problem. In this study, we propose a novel single-input MA reduction algorithm
based on time-variant forward-backward harmonic notch filtering. To verify the
proposed method, we collected real PPG data corrupted by MA and compared it with
existing single-input MA reduction methods. In conclusion, the proposed zero
phase line enhancer (ZLE) was found to be superior for MA reduction and exhibited
zero phase response.
PMID- 28420088
TI - Range Analysis of Thermal Stress and Optimal Design for Tungsten-Rhenium Thin
Film Thermocouples Based on Ceramic Substrates.
AB - A thermal stress range analysis of tungsten-rhenium thin film thermocouples based
on ceramic substrates is presented to analyze the falling off and breakage
problems caused by the mismatch of the thermal stresses in thin film
thermocouples (TFTCs) and substrate, and nano-indentation experiments are done to
measure and calculate the film stress to compare with the simulation results.
Optimal design and fabrication of tungsten-rhenium TFTCs based on ceramic
substrates is reported. Static high temperature tests are carried out, which show
the optimization design can effectively reduce the damage caused by the thermal
stress mismatch.
PMID- 28420087
TI - Skeletal Muscle Nucleo-Mitochondrial Crosstalk in Obesity and Type 2 Diabetes.
AB - Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation
and accumulation of fatty acid intermediates in the form of long and medium chain
acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance
during high fat diet (HFD)-induced obesity. The present review discusses the
roles of anterograde and retrograde communication in nucleo-mitochondrial
crosstalk that determines skeletal muscle mitochondrial adaptations, specifically
alterations in mitochondrial number and function in relation to obesity and
insulin resistance. Special emphasis is placed on the effects of high fat diet
(HFD) feeding on expression of nuclear-encoded mitochondrial genes (NEMGs)
nuclear receptor factor 1 (NRF-1) and 2 (NRF-2) and peroxisome proliferator
receptor gamma coactivator 1 alpha (PGC-1alpha) in the onset and progression of
insulin resistance during obesity and how HFD-induced alterations in NEMG
expression affect skeletal muscle mitochondrial adaptations in relation to beta
oxidation of fatty acids. Finally, the potential ability of acylcarnitines or
fatty acid intermediates resulting from mitochondrial beta oxidation to act as
retrograde signals in nucleo-mitochondrial crosstalk is reviewed and discussed.
PMID- 28420089
TI - Suppression of GHS-R in AgRP Neurons Mitigates Diet-Induced Obesity by Activating
Thermogenesis.
AB - Ghrelin, an orexigenic hormone released primarily from the gut, signals the
hypothalamus to stimulate growth hormone release, enhance appetite and promote
weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS
R), is highly expressed in the brain, with highest expression in Agouti-Related
Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron
specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice
by activating non-shivering thermogenesis. To further decipher the specific
neuronal circuits mediating the metabolic effects of GHS-R, we generated AgRP
neuron-specific GHS-R knockout mice (AgRP-Cre;Ghsrf/f). Our data showed that GHS
R in AgRP neurons is required for ghrelin's stimulatory effects on growth hormone
secretion, acute food intake and adiposity, but not for long-term total food
intake. Importantly, deletion of GHS-R in AgRP neurons attenuated diet-induced
obesity (DIO) and enhanced cold-resistance in mice fed high fat diet (HFD). The
HFD-fed knockout mice showed increased energy expenditure, and exhibited enhanced
thermogenic activation in both brown and subcutaneous fat; this implies that GHS
R suppression in AgRP neurons enhances sympathetic outflow. In summary, our
results suggest that AgRP neurons are key site for GHS-R mediated thermogenesis,
and demonstrate that GHS-R in AgRP neurons plays crucial roles in governing
energy utilization and pathogenesis of DIO.
PMID- 28420090
TI - Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific
Endoribonuclease Activity.
AB - Protein translation is the most common target of toxin-antitoxin system (TA)
toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific
manner, thereby blocking translation. While past studies mainly focused on the
digestion of mRNA, recent analysis revealed that toxins can also digest tRNA,
rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA
containing recognition sequences in the absence of ribosome in vitro. However,
increasing evidence suggests that in vivo digestion may occur in association with
ribosomes. Despite the prevalence of recognition sequences in many mRNA,
preferential digestion seems to occur at specific positions within mRNA and also
in certain reading frames. In this review, a variety of tools utilized to study
the nuclease activities of toxins over the past 15 years will be reviewed. A
recent adaptation of an RNA-seq-based technique to analyze entire sets of
cellular RNA will be introduced with an emphasis on its strength in identifying
novel targets and redefining recognition sequences. The differences in
biochemical properties and postulated physiological roles will also be discussed.
PMID- 28420091
TI - Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts:
Emerging Mechanisms of Disease.
AB - The rapid increase in metabolic diseases, which occurred in the last three
decades in both industrialized and developing countries, has been related to the
rise in sugar-added foods and sweetened beverages consumption. An emerging topic
in the pathogenesis of metabolic diseases related to modern nutrition is the role
of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high
temperature processed foods, but also endogenously formed as a consequence of a
high dietary sugar intake. Animal models of high sugar consumption, in particular
fructose, have reported AGE accumulation in different tissues in association with
peripheral insulin resistance and lipid metabolism alterations. The in vitro
observation that fructose is one of the most rapid and effective glycating agents
when compared to other sugars has prompted the investigation of the in vivo
fructose-induced glycation. In particular, the widespread employment of fructose
as sweetener has been ascribed by many experimental and observational studies for
the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet
derived AGEs have been demonstrated to interfere with many cell functions such as
lipid synthesis, inflammation, antioxidant defences, and mitochondrial
metabolism. Moreover, emerging evidence also in humans suggest that this impact
of dietary AGEs on different signalling pathways can contribute to the onset of
organ damage in liver, skeletal and cardiac muscle, and the brain, affecting not
only metabolic control, but global health. Indeed, the most recent reports on the
effects of high sugar consumption and diet-derived AGEs on human health reviewed
here suggest the need to limit the dietary sources of AGEs, including added
sugars, to prevent the development of metabolic diseases and related
comorbidities.
PMID- 28420092
TI - Analysis of Sub-Lethal Toxicity of Perfluorooctane Sulfonate (PFOS) to Daphnia
magna Using 1H Nuclear Magnetic Resonance-Based Metabolomics.
AB - 1H nuclear magnetic resonance (NMR)-based metabolomics was used to characterize
the response of Daphnia magna after sub-lethal exposure to perfluorooctane
sulfonate (PFOS), a commonly found environmental pollutant in freshwater
ecosystems. Principal component analysis (PCA) scores plots showed significant
separation in the exposed samples relative to the controls. Partial least squares
(PLS) regression analysis revealed a strong linear correlation between the
overall metabolic response and PFOS exposure concentration. More detailed
analysis showed that the toxic mode of action is metabolite-specific with some
metabolites exhibiting a non-monotonic response with higher PFOS exposure
concentrations. Our study indicates that PFOS exposure disrupts various energy
metabolism pathways and also enhances protein degradation. Overall, we identified
several metabolites that are sensitive to PFOS exposure and may be used as
bioindicators of D. magna health. In addition, this study also highlights the
important utility of environmental metabolomic methods when attempting to
elucidate acute and sub-lethal pollutant stressors on keystone organisms such as
D. magna.
PMID- 28420093
TI - Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and
Primary Sjogren's Syndrome.
AB - Clinical studies have shown that metabolic disorders such as type 2 diabetes and
dyslipidemia are associated with increased risk of oral-related diseases, such as
periodontitis and Sjogren's syndrome. Although changes in the immune system are
critical in both of these metabolic disorders and oral-related diseases, the
mechanism underlying the interaction between these diseases remains largely
unknown. Obesity and type 2 diabetes are known to be associated with higher
concentrations of free fatty acids in blood. Among free fatty acids, saturated
fatty acids such as palmitic acid have been demonstrated to induce inflammatory
responses mainly via the innate immune systems, and to be involved in the
pathogenesis of type 2 diabetes in tissues such as adipose tissue, liver,
pancreas, and skeletal muscle. Here, we highlight recent advances in evidence for
the potential involvement of palmitic acid in the pathogenesis of periodontitis
and Sjogren's syndrome, and discuss the possibility that improvement of the lipid
profile could be a new strategy for the treatment of these diseases.
PMID- 28420095
TI - Parenteral Nutrition and Lipids.
AB - Lipids have multiple physiological roles that are biologically vital. Soybean oil
lipid emulsions have been the mainstay of parenteral nutrition lipid formulations
for decades in North America. Utilizing intravenous lipid emulsions in parenteral
nutrition has minimized the dependence on dextrose as a major source of
nonprotein calories and prevents the clinical consequences of essential fatty
acid deficiency. Emerging literature has indicated that there are benefits to
utilizing alternative lipids such as olive/soy-based formulations, and
combination lipids such as soy/MCT/olive/fish oil, compared with soybean based
lipids, as they have less inflammatory properties, are immune modulating, have
higher antioxidant content, decrease risk of cholestasis, and improve clinical
outcomes in certain subgroups of patients. The objective of this article is to
review the history of IVLE, their composition, the different generations of
widely available IVLE, the variables to consider when selecting lipids, and the
complications of IVLE and how to minimize them.
PMID- 28420094
TI - Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and
Potential New Treatments.
AB - Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver
disorders worldwide. It is associated with clinical states such as obesity,
insulin resistance, and type 2 diabetes, and covers a wide range of liver
changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH),
liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid
accumulation, insulin resistance, and inflammation, have been implicated in the
pathogenesis of NAFLD, but the underlying mechanisms, including those that drive
disease progression, are not fully understood. Both innate and recruited immune
cells mediate the development of insulin resistance and NASH. Therefore,
modifying the polarization of resident and recruited macrophage/Kupffer cells is
expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also
pivotal for the progression of NASH, which has generated interest in carotenoids
as potent micronutrient antioxidants in the treatment of NAFLD. In addition to
their antioxidative function, carotenoids regulate macrophage/Kupffer cell
polarization and thereby prevent NASH progression. In this review, we summarize
the molecular mechanisms involved in the pathogenesis of NAFLD, including
macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We
also discuss dietary antioxidants, such as beta-cryptoxanthin and astaxanthin,
that may be effective in the prevention or treatment of NAFLD.
PMID- 28420096
TI - A Network-Based Pharmacology Study of the Herb-Induced Liver Injury Potential of
Traditional Hepatoprotective Chinese Herbal Medicines.
AB - Herbal medicines are widely used for treating liver diseases and generally
regarded as safe due to their extensive use in Traditional Chinese Medicine
practice for thousands of years. However, in recent years, there have been
increased concerns regarding the long-term risk of Herb-Induced Liver Injury
(HILI) in patients with liver dysfunction. Herein, two representative Chinese
herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other
Radix Polygoni Multiflori (Heshouwu)-a single herb, were analyzed by network
pharmacology study. Based on the network pharmacology framework, we exploited the
potential HILI effects of XCHT and Heshouwu by predicting the molecular
mechanisms of HILI and identified the potential hepatotoxic ingredients in XCHT
and Heshouwu. According to our network results, kaempferol and thymol in XCHT and
rhein in Heshouwu exhibit the largest number of liver injury target connections,
whereby CASP3, PPARG and MCL1 may be potential liver injury targets for these
herbal medicines. This network pharmacology assay might serve as a useful tool to
explore the underlying molecular mechanism of HILI. Based on the theoretical
predictions, further experimental verification should be performed to validate
the accuracy of the predicted interactions between herbal ingredients and protein
targets in the future.
PMID- 28420097
TI - Synthesis of Curcuminoids and Evaluation of Their Cytotoxic and Antioxidant
Properties.
AB - Curcumin (1) and ten derivatives (2-11) were synthesized and evaluated as
cytotoxic and antioxidant agents. The results of primary screening by
Sulforhodamine B assay against five human cancer cell lines (U-251 MG,
glioblastoma; PC-3, human prostatic; HCT-15, human colorectal; K562, human
chronic myelogenous leukemia; and SKLU-1, non-small cell lung cancer) allowed us
to calculate the half maximal inhibitory concentration (IC50) values for the more
active compounds against HCT-15 and K562 cell lines. Compounds 2 and 10 were the
most active against both cell lines and were more active than curcumin itself.
Thiobarbituric acid reactive substances (TBARS) assay showed that 7 has potent
activity; even stronger than curcumin, alpha-tocopherol, and quercetin.
PMID- 28420098
TI - Development and Validation of a Questionnaire to Assess Knowledge, Threat and
Coping Appraisal, and Intention to Practice Healthy Behaviors Related to Non
Communicable Diseases in the Thai Population.
AB - Non-communicable diseases (NCDs) are important issues in Thailand and health
sectors are now focusing on modifiable risks that include cognitive, affective
and behavioral factors. This study aimed to develop and validate a questionnaire
to assess knowledge about NCDs, threat appraisal, coping appraisal and intention
to practice based on protection motivation theory. Content validity was
determined by the mean of the item content validity index (I-CVI) from five
experts. The questionnaire was pilot tested for difficulty of knowledge items and
reliability test using the Kuder-Richardson (KR)-20 and Cronbach's alpha
coefficient among 30 Thai adult subjects in the health office for two sub
districts. The mean I-CVI ranged from 0.90-1.00 and difficulty of knowledge
ranged from 0.3-0.9. The reliability test of knowledge by KR-20 ranged from 0.648
0.799, while Cronbach's alpha coefficients of threat and coping appraisal and
intention to practice ranged from 0.70-0.843. We compared sociodemographic data,
knowledge about NCDs, threat appraisal, coping appraisal and intention to
practice between 50 diabetic type 2 cases and 50 controls. T2DM cases had higher
age, knowledge scores on diabetes and hypertension, threat appraisal scores on
hypertension and cardiovascular disease when compared with control (p < 0.05).
The questionnaire was valid and sufficiently reliable to use for data collection.
PMID- 28420100
TI - Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf.
Caldora penicillata.
AB - A bioactivity guided study of a cf. Caldora penicillata species, collected during
a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a
commonwealth of the USA), led to the isolation of a new thiazoline-containing
alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of
the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded
dimeric compound that was isolated previously from a Fijian marine
cyanobacterium. The structure and absolute configuration of laucysteinamide A (1)
was determined by a detailed analysis of its NMR, MS, and CD spectra. In
addition, the highly bioactive lipid, curacin D (3), was also found to be present
in this cyanobacterial extract. The latter compound was responsible for the
potent cytotoxicity of this extract to H-460 human non-small cell lung cancer
cells in vitro.
PMID- 28420101
TI - The Effect of Citrus Essential Oils and Their Constituents on Growth of
Xanthomonas citri subsp. citri.
AB - Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is
the most devastating of the citrus diseases worldwide. During our study, we found
that Essential oils (EOs) of some citrus cultivars are effective on Xcc.
Therefore, it prompted us to determine the plant metabolites responsible for the
antibacterial properties. We obtained EOs from some locally cultivated citrus by
using a Clevenger apparatus and their major constituents were identified by gas
chromatography/mass spectrometry (GC-MS). The effect of Citrus aurantium, C.
aurantifolia, Fortunella sp. EOs and their major constituents were evaluated
against Xcc-KVXCC1 using a disk diffusion assay. Minimal inhibitory and
bactericidal concentration of the EOs and their constituents were determined
using the broth microdilution method. C. aurantium, C. aurantifolia Eos, and
their major constituents including citral, linalool, citronellal, geraniol, alpha
terpineol, and linalyl acetate indicated antibacterial effects against Xcc. The
C. aurantifolia EO and citral showed the highest antibacterial activity among the
tested EOs and constituents with inhibition zones of 15 +/- 0.33 mm and 16.67 +/-
0.88 mm, respectively. Synergistic effects of the constituents were observed
between alpha-terpineol-citral, citral-citronellal, citral-geraniol, and
citronellal-geraniol by using a microdilution checkerboard assay. Transmission
electron microscopy revealed that exposure of Xcc cells to citral caused cell
wall damage and altered cytoplasmic density. We introduced C. aurantifolia and C.
aurantium EOs, and their constituents citral, alpha-terpineol, citronellal,
geraniol, and linalool as possible control agents for CBC.
PMID- 28420102
TI - Efficient Actor Recovery Paradigm for Wireless Sensor and Actor Networks.
AB - The actor nodes are the spine of wireless sensor and actor networks (WSANs) that
collaborate to perform a specific task in an unverified and uneven environment.
Thus, there is a possibility of high failure rate in such unfriendly scenarios
due to several factors such as power consumption of devices, electronic circuit
failure, software errors in nodes or physical impairment of the actor nodes and
inter-actor connectivity problem. Therefore, it is extremely important to
discover the failure of a cut-vertex actor and network-disjoint in order to
improve the Quality-of-Service (QoS). In this paper, we propose an Efficient
Actor Recovery (EAR) paradigm to guarantee the contention-free traffic-forwarding
capacity. The EAR paradigm consists of a Node Monitoring and Critical Node
Detection (NMCND) algorithm that monitors the activities of the nodes to
determine the critical node. In addition, it replaces the critical node with
backup node prior to complete node-failure which helps balancing the network
performance. The packets are handled using Network Integration and Message
Forwarding (NIMF) algorithm that determines the source of forwarding the packets;
either from actor or sensor. This decision-making capability of the algorithm
controls the packet forwarding rate to maintain the network for a longer time.
Furthermore, for handling the proper routing strategy, Priority-Based Routing for
Node Failure Avoidance (PRNFA) algorithm is deployed to decide the priority of
the packets to be forwarded based on the significance of information available in
the packet. To validate the effectiveness of the proposed EAR paradigm, the
proposed algorithms were tested using OMNET++ simulation.
PMID- 28420099
TI - Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids:
Facts and Artifacts.
AB - Na+,K+-ATPase is the only known receptor of cardiotonic steroids (CTS) whose
interaction with catalytic alpha-subunits leads to inhibition of this enzyme. As
predicted, CTS affect numerous cellular functions related to the maintenance of
the transmembrane gradient of monovalent cations, such as electrical membrane
potential, cell volume, transepithelial movement of salt and osmotically-obliged
water, symport of Na+ with inorganic phosphate, glucose, amino acids,
nucleotides, etc. During the last two decades, it was shown that side-by-side
with these canonical Na+i/K+i-dependent cellular responses, long-term exposure to
CTS affects transcription, translation, tight junction, cell adhesion and
exhibits tissue-specific impact on cell survival and death. It was also shown
that CTS trigger diverse signaling cascades via conformational transitions of the
Na+,K+-ATPase alpha-subunit that, in turn, results in the activation of membrane
associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and
the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to
propose that endogenous CTS might be considered as a novel class of steroid
hormones. We focus our review on the analysis of the relative impact Na+i,K+i
mediated and -independent pathways in cellular responses evoked by CTS.
PMID- 28420103
TI - Electrochemical Genosensing of Circulating Biomarkers.
AB - Management and prognosis of diseases requires the measurement in non- or
minimally invasively collected samples of specific circulating biomarkers,
consisting of any measurable or observable factors in patients that indicate
normal or disease-related biological processes or responses to therapy.
Therefore, on-site, fast and accurate determination of these low abundance
circulating biomarkers in scarcely treated body fluids is of great interest for
health monitoring and biological applications. In this field, electrochemical DNA
sensors (or genosensors) have demonstrated to be interesting alternatives to more
complex conventional strategies. Currently, electrochemical genosensors are
considered very promising analytical tools for this purpose due to their fast
response, low cost, high sensitivity, compatibility with microfabrication
technology and simple operation mode which makes them compatible with point-of
care (POC) testing. In this review, the relevance and current challenges of the
determination of circulating biomarkers related to relevant diseases (cancer,
bacterial and viral infections and neurodegenerative diseases) are briefly
discussed. An overview of the electrochemical nucleic acid-based strategies
developed in the last five years for this purpose is given to show to both
familiar and non-expert readers the great potential of these methodologies for
circulating biomarker determination. After highlighting the main features of the
reported electrochemical genosensing strategies through the critical discussion
of selected examples, a conclusions section points out the still existing
challenges and future directions in this field.
PMID- 28420104
TI - Low Power Near Field Communication Methods for RFID Applications of SIM Cards.
AB - Power consumption and communication distance have become crucial challenges for
SIM card RFID (radio frequency identification) applications. The combination of
long distance 2.45 GHz radio frequency (RF) technology and low power 2 kHz near
distance communication is a workable scheme. In this paper, an ultra-low
frequency 2 kHz near field communication (NFC) method suitable for SIM cards is
proposed and verified in silicon. The low frequency transmission model based on
electromagnetic induction is discussed. Different transmission modes are
introduced and compared, which show that the baseband transmit mode has a better
performance. The low-pass filter circuit and programmable gain amplifiers are
applied for noise reduction and signal amplitude amplification. Digital-to-analog
converters and comparators are used to judge the card approach and departure. A
novel differential Manchester decoder is proposed to deal with the internal clock
drift in range-controlled communication applications. The chip has been fully
implemented in 0.18 um complementary metal-oxide-semiconductor (CMOS) technology,
with a 330 uA work current and a 45 uA idle current. The low frequency chip can
be integrated into a radio frequency SIM card for near field RFID applications.
PMID- 28420105
TI - One-Year Results of a Synthetic Intervention Model for the Primary Prevention of
T2D among Elderly Individuals with Prediabetes in Rural China.
AB - Objective: The objective of this study was to evaluate the effectiveness of a
synthetic intervention model aimed at preventing type 2 diabetes and controlling
plasma glucose, body weight and waist circumference in elderly individuals with
prediabetes in rural China. Methods: We randomly assigned 434 (180 men and 254
women; mean age, 69 years; mean body mass index, 23.6 kg/m2) with prediabetes to
either the intervention group or the control group. Each participant in the
intervention group received synthetic intervention for 1 year. Results: The
incidence of diabetes was 4.2% in the intervention group, versus 19.7% in the
control group at the end of 1 year (p < 0.001). Compared with the control group,
the intervention group experienced a great decrease in fasting glucose (-3.9 vs.
2.2 mg/dL, p < 0.001), body weight (-3.2 vs. 1.7 kg, p < 0.001), waist
circumference (-2.4 vs. 1.0 cm, p < 0001), total cholesterol (-9.1 vs. -4.6
mg/dL. p = 0.014) and HbA1c (-1.0 vs. 0.1 mg %, p = 0.002) at the end of 1 year.
Conclusions: The incidence of diabetes of the control group was higher than that
of the intervention group. Besides, the synthetic intervention contributes to
weight loss and glucose decrease, and may be effective in reducing the risk of
diabetes among elderly individuals with prediabetes in rural China.
PMID- 28420106
TI - Temporary Black Henna Tattoos and Sensitization to para-Phenylenediamine (PPD):
Two Paediatric Case Reports and a Review of the Literature.
AB - Background: The use of temporary henna tattoos has increased dramatically in
recent years, especially in children and adolescents. To obtain a darker colour
and prolong the life of the tattoo, red henna, a plant-derived substance, is
typically added to para-phenylenediamine (PPD). The mixture is called temporary
black henna tattoo (TBHT). Because of its molecular characteristics, PPD can
induce skin sensitization that may cause various clinical manifestations with
successive exposures, among which the most common is allergic contact dermatitis
(ACD). This report describes two paediatric cases of PPD sensitization and ACD
after the exposure to TBHT and summarizes the literature on this emerging
clinical problem. Case Presentation: We describe two cases of childhood-onset ACD
that occurred 2 and 10 days, respectively, after the application of a TBHT during
the summer holidays. Patch tests showed an evident positive response to 1% PPD in
both cases. Sensitization to PPD occurred in the first case because a previous
henna tattoo did not result in overt symptoms; in the second case, the reaction
occurred after the same tattoo was retouched. In both cases, hypopigmentation
persisted and both the patients and their families were advised to avoid further
contact with PPD-containing materials and substances that could lead to cross
reactions. Conclusions: Sensitization to PPD is a growing phenomenon in children.
The most common cause appears to be exposure to TBHT in which PPD might be
present at unknown or high concentrations. Once sensitization occurs, patients
may experience severe clinical symptoms which can present with a persistent
hypopigmentation when they are re-exposed to substances that contain or cross
react with PPD. Given the widespread use of PPD, TBHT could adversely affect the
daily life of paediatric patients; thus, for this reason, this practice as a
fashion accessory must be discouraged. In addition, it is extremely important to
provide scientific information on the risks of TBHT to consumers, especially to
adolescents and to the parents of younger children to prevent PPD sensitization.
PMID- 28420107
TI - Prepartum Lying Behavior of Holstein Dairy Cows Housed on Pasture through
Parturition.
AB - Utilizing pasture-based systems may increase cow comfort during late gestation
and calving as it lacks the constraints of confinement housing. The objective of
this study was to quantify lying behavior and activity of Holstein dairy cows
housed on pasture during the 6 d before calving. Sixteen Holstein dairy cows were
moved to pasture 3 weeks before their projected calving date. Data loggers were
attached 14 d prior to projected calving date. Behavior was evaluated 6 d before
calving for all cows (n = 16) and 6 h prior to calving for a subset of cows (n =
6) with known calving times. Data loggers recorded at 1-min intervals to
determine lying time (h/d and %/h), lying bouts (n/d and n/h), lying bout
duration (min/bout), and steps (n/d and n/h). A repeated measures analysis of
variance with contrasts was performed to determine if lying behaviors and
activity differed between baseline and day or hour of interest. Lying time was
greater 6 d prior to calving compared to the day of and before calving. Cows had
longer lying bouts 6 d prior to calving compared to day of calving. Cows spent
less time lying in the hour before calving compared to 6 h prior to parturition.
The lack of change in behavior and activity during the 7 d prior to calving may
indicate that pasture provided an adequate environment for cows during the
prepartum period but did not impact cow welfare in the hours leading up to
calving.
PMID- 28420108
TI - A Robust Crowdsourcing-Based Indoor Localization System.
AB - WiFi fingerprinting-based indoor localization has been widely used due to its
simplicity and can be implemented on the smartphones. The major drawback of WiFi
fingerprinting is that the radio map construction is very labor-intensive and
time-consuming. Another drawback of WiFi fingerprinting is the Received Signal
Strength (RSS) variance problem, caused by environmental changes and device
diversity. RSS variance severely degrades the localization accuracy. In this
paper, we propose a robust crowdsourcing-based indoor localization system
(RCILS). RCILS can automatically construct the radio map using crowdsourcing data
collected by smartphones. RCILS abstracts the indoor map as the semantics graph
in which the edges are the possible user paths and the vertexes are the location
where users may take special activities. RCILS extracts the activity sequence
contained in the trajectories by activity detection and pedestrian dead
reckoning. Based on the semantics graph and activity sequence, crowdsourcing
trajectories can be located and a radio map is constructed based on the
localization results. For the RSS variance problem, RCILS uses the trajectory
fingerprint model for indoor localization. During online localization, RCILS
obtains an RSS sequence and realizes localization by matching the RSS sequence
with the radio map. To evaluate RCILS, we apply RCILS in an office building.
Experiment results demonstrate the efficiency and robustness of RCILS.
PMID- 28420109
TI - Comparison of Biogenic Amines and Mycotoxins in Alfalfa and Red Clover Fodder
Depending on Additives.
AB - In the production of fermented feed, each crop can be contaminated with a variety
of microorganisms that may produce natural pollutants. Biogenic amines,
mycotoxins, and undesirable organic acids can decrease health feed safety. The
aim of this study was to compare the counts of microorganisms, levels of biogenic
amines, and the mycotoxins in forage legumes, and also to compare the occurrence
of microorganisms and levels of mycotoxins in green fodder and subsequently
produced silage and the influence of additives on the content of natural harmful
substances in silage. The experimental plot was located in Troubsko and Vatin, in
the Czech Republic. Two varieties of Medicago sativa and one variety of Trifolium
pratense were compared. Green fodder and subsequently produced silage reaching up
to 23% of dry matter were evaluated and prepared using a bio-enzymatic additive
and a chemical additive. Green fodder of Medicago sativa was more contaminated by
Enterococci than Trifolium pratense fodder. The obvious difference was determined
by the quality of silage leachate. The silage prepared from Medicago sativa
fodder was more contaminated with butyric acid. Fungi were present in higher
counts in the anaerobic environment of green fodder and contaminated it with
zearalenone and deoxynivalenol. Lower counts of fungi were found in silage,
although the zearalenone content did not change. Lower content of deoxynivalenol
was detected in silage, compared with green fodder. Silages treated with a
chemical additive were found not to contain butyric acid. Lower ethanol content
was determined, and the tendency to reduce the risk of biogenic amines occurrence
was evident. The additives proved to have no influence on the content of
mycotoxins.
PMID- 28420110
TI - Chemical Sensors and Biosensors in Italy: A Review of the 2015 Literature.
AB - The contributions of Italian researchers to sensor research in 2015 is reviewed.
The analysis of the activities in one year allows one to obtain a snapshot of the
Italian scenario capturing the main directions of the research activities.
Furthermore, the distance of more than one year makes meaningful the bibliometric
analysis of the reviewed papers. The review shows a research community
distributed among different scientific disciplines, from chemistry, physics,
engineering, and material science, with a strong interest in collaborative works.
PMID- 28420111
TI - Plantago asiatica L. Ameliorates Puromycin Aminonucleoside-Induced Nephrotic
Syndrome by Suppressing Inflammation and Apoptosis.
AB - OBJECTIVE: Nephrotic syndrome, a kidney disease with a variety of causes, is
mainly characterized by heavy proteinuria, hypoproteinemia, and ascites. This
study was designed to evaluate the underlying mechanism of action of Plantago
asiatica L. (PAL) in treating nephrotic syndrome induced by puromycin
aminonucleoside. METHODS: PAL has been used in Asia as a traditional medicine and
dietary health supplement. Sprague-Dawley (SD) rats were intravenously injected
with puromycin aminonucleoside (75 mg/kg/day), then treated with either Losartan
(30 mg/kg/day) or PAL (200 mg/kg/day) by oral gavage for seven days. RESULTS: PAL
significantly decreased ascites, proteinuria level, and plasma lipid parameters.
In addition, treatment with PAL attenuated histological damage and
hypoalbuminemia. Treatment with PAL also restored podocin expression and reduced
inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte
chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and high
mobility group box-1 (HMGB1). Lower expression levels of the apoptosis markers
Bax, caspase-3 and capase-9 were documented in SD rats receiving PAL. PAL also
significantly decreased the phosphorylation levels of MAPKs such as ERK, JNK and
p38. CONCLUSION: As a multifunctional agent, PAL has a renoprotective effect in
nephrotic syndrome rat models. The anti-inflammatory and anti-apoptotic
properties, along with reductions in hyperlipidemia and ascites, represent
important therapeutic effects. These results indicate that Plantago asiatica is
likely to be a promising agent in the treatment of nephrotic syndrome.
PMID- 28420112
TI - The Association between Breakfast Skipping and Body Weight, Nutrient Intake, and
Metabolic Measures among Participants with Metabolic Syndrome.
AB - The effect of skipping breakfast on health, especially in adults, remains a
controversial topic. A secondary data analysis was conducted to examine
associations between breakfast eating patterns and weight loss, nutrient intake,
and metabolic parameters among participants with metabolic syndrome (MetS) (n =
240). Three randomly selected 24-h dietary recalls were collected from each
participant at baseline and at the one-year visit. Skipped breakfast was seen in
32.9% at baseline and in 17.4% at the one-year visit, respectively. At baseline,
after adjustment for demographics and physical activity, participants who ate
breakfast had a higher thiamin, niacin, and folate intake than did breakfast
skippers (p < 0.05); other selected parameters including body weight, dietary
quality scores, nutrient intake, and metabolic parameters showed no significant
differences between the two groups (p >= 0.05). From baseline to one year, after
adjustment for covariates, mean fat intake increased by 2.7% (95% confidence
intervals (CI): -1.0, 6.5%) of total energy in breakfast skippers in comparison
to the 1.2% decrease observed in breakfast eaters (95% CI: -3.4, 1.1%) (p =
0.02). Mean changes in other selected parameters showed no significant
differences between breakfast skippers and eaters (p > 0.05). This study did not
support the hypothesis that skipping breakfast has impact on body weight,
nutrient intakes, and selected metabolic measures in participants with MetS.
PMID- 28420113
TI - Synthesis and Spectral Properties of meso-Arylbacteriochlorins, Including
Insights into Essential Motifs of their Hydrodipyrrin Precursors.
AB - Synthetic bacteriochlorins-analogues of bacteriochlorophylls, Nature's near
infrared absorbers-are attractive for diverse photochemical studies. meso
Arylbacteriochlorins have been prepared by the self-condensation of a
dihydrodipyrrin-carbinol or dihydrodipyrrin-acetal following an Eastern-Western
(E-W) or Northern-Southern (N-S) joining process. The bacteriochlorins bear a gem
dimethyl group in each pyrroline ring to ensure stability toward oxidation. The
two routes differ in the location of the gem-dimethyl group at the respective 3-
or 2-position in the dihydrodipyrrin, and the method of synthesis of the
dihydrodipyrrin. Treatment of a known 3,3-dimethyldihydrodipyrrin-1
carboxaldehyde with an aryl Grignard reagent afforded the dihydrodipyrrin-1
(aryl)carbinol, and upon subsequent acetylation, the corresponding
dihydrodipyrrin-1-methyl acetate (dihydrodipyrrin-acetate). Self-condensation of
the dihydrodipyrrin-acetate gave a meso-diarylbacteriochlorin (E-W route). A 2,2
dimethyl-5-aryldihydrodipyrrin-1-(aryl)carbinol underwent self-condensation to
give a trans-A2B2-type meso-tetraarylbacteriochlorin (N-S route). In each case,
the aromatization process entails a 2e-/2H+ (aerobic) dehydrogenative oxidation
following the dihydrodipyrrin self-condensation. Comparison of a
tetrahydrodipyrrin-acetal (0%) versus a dihydrodipyrrin-acetal (41%) in
bacteriochlorin formation and results with various 1-substituted dihydrodipyrrins
revealed the importance of resonance stabilization of the reactive hydrodipyrrin
intermediate. Altogether 10 new dihydrodipyrrins and five new bacteriochlorins
have been prepared. The bacteriochlorins exhibit characteristic
bacteriochlorophyll-like absorption spectra, including a Qy band in the region
726-743 nm.
PMID- 28420114
TI - Fuzzy System-Based Target Selection for a NIR Camera-Based Gaze Tracker.
AB - Gaze-based interaction (GBI) techniques have been a popular subject of research
in the last few decades. Among other applications, GBI can be used by persons
with disabilities to perform everyday tasks, as a game interface, and can play a
pivotal role in the human computer interface (HCI) field. While gaze tracking
systems have shown high accuracy in GBI, detecting a user's gaze for target
selection is a challenging problem that needs to be considered while using a gaze
detection system. Past research has used the blinking of the eyes for this
purpose as well as dwell time-based methods, but these techniques are either
inconvenient for the user or requires a long time for target selection.
Therefore, in this paper, we propose a method for fuzzy system-based target
selection for near-infrared (NIR) camera-based gaze trackers. The results of
experiments performed in addition to tests of the usability and on-screen
keyboard use of the proposed method show that it is better than previous methods.
PMID- 28420116
TI - Construct Validity of an Obesity Risk Screening Tool in Two Age Groups.
AB - Home environment influences child health, but the impact varies as children move
into adolescence. The Family Nutrition and Physical Activity (FNPA) screening
tool has been used to evaluate home environments, but studies have not compared
the utility of the tool in different age groups. The purpose of this study was to
examine the efficacy of the FNPA tool in first and tenth grade samples. Parents
of first grade (n = 250) and tenth grade (n = 99) students completed the FNPA and
results were linked to body mass index (BMI) data. FNPA scores were examined by
gender, income, race, and school-level socioeconomic status (SES). Correlations
examined associations between FNPA scores and several BMI indicators. Logistic
and linear regression analyses evaluated the construct validity of the FNPA in
both groups. Mean FNPA score differed by age group, by SES in both age groups,
and by race in the first grade sample only. Correlations between FNPA score and
BMI indicators were higher in the first grade sample, but SES was significantly
associated with BMI only in tenth graders. The FNPA has stronger utility in
younger children, while school SES is a stronger predictor of adolescent weight
status.
PMID- 28420115
TI - A Cross-Sectional Study on Selected Correlates of High risk Sexual Behavior in
Polish Migrants Resident in the United Kingdom.
AB - Objective: To assess the correlates of the high risk sexual behaviors of Polish
migrants in the United Kingdom (UK) after 2004, and to compare such behaviors
before/after immigration. Methods: In 2013, a cross-sectional study was conducted
through the use of a Computer-assisted web interviewing surveying technique with
the use of a self-administered questionnaire. Results: Among 408 respondents
(56.9% women), with a median age of 32 years, significantly more admitted to
having unprotected sexual contact with a casual partner while in the UK (p <
0.0001) than while in Poland; more were engaged in sex after the use of
recreational drugs and alcohol (p < 0.0001 and p = 0.001 respectively). Being a
male was associated with greater odds of unprotected sex, sex after the use of
alcohol, and having multiple partners. Being single and having only been a
resident for a short time in the UK, presenting a lower self-esteem, were
predictors of unprotected sex. A total of 19.6% of the respondents admitted to
having been tested while in Poland, a lower (p < 0.0001) frequency than while in
the UK (49.5%); this referred to both genders; 1.2% (95% CI: 0.79-2.83%) reported
that they were HIV positive. Conclusions: Migration can create a vulnerability to
STIs, especially for single male migrants with low self-esteem, staying in the UK
for less than two years. The results point to strengthening strategies which help
reduce high risk sexual behavior among Polish migrants, and to introduce
interventions to promote an awareness of HIV sero-status.
PMID- 28420117
TI - Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with
Cisplatin on Ovarian Cancer Cells.
AB - Melittin, the main peptide present in bee venom, has been proposed as having
potential for anticancer therapy; the addition of melittin to cisplatin, a first
line treatment for ovarian cancer, may increase the therapeutic response in
cancer treatment via synergy, resulting in improved tolerability, reduced
relapse, and decreased drug resistance. Thus, this study was designed to compare
the metabolomic effects of melittin in combination with cisplatin in cisplatin
sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid
chromatography (LC) coupled with mass spectrometry (MS) was applied to identify
metabolic changes in A2780 (combination treatment 5 MUg/mL melittin + 2 MUg/mL
cisplatin) and A2780CR (combination treatment 2 MUg/mL melittin + 10 MUg/mL
cisplatin) cells. Principal components analysis (PCA) and orthogonal partial
least squares discriminant analysis (OPLS-DA) multivariate data analysis models
were produced using SIMCA-P software. All models displayed good separation
between experimental groups and high-quality goodness of fit (R2) and goodness of
prediction (Q2), respectively. The combination treatment induced significant
changes in both cell lines involving reduction in the levels of metabolites in
the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and
pyrimidine metabolism, and the arginine/proline pathway. The combination of
melittin with cisplatin that targets these pathways had a synergistic effect. The
melittin-cisplatin combination had a stronger effect on the A2780 cell line in
comparison with the A2780CR cell line. The metabolic effects of melittin and
cisplatin in combination were very different from those of each agent alone.
PMID- 28420118
TI - Ambient Air Pollution and Out-of-Hospital Cardiac Arrest in Beijing, China.
AB - Air pollutants are associated with cardiovascular death; however, there is
limited evidence of the effects of different pollutants on out-of-hospital
cardiac arrests (OHCAs) in Beijing, China. We aimed to investigate the
associations of OHCAs with the air pollutants PM2.5-10 (coarse particulate
matter), PM2.5 (particles <=2.5 MUm in aerodynamic diameter), nitrogen dioxide
(NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) between 2013
and 2015 using a time-stratified case-crossover study design. We obtained health
data from the nationwide emergency medical service database; 4720 OHCA cases of
cardiac origin were identified. After adjusting for relative humidity and
temperature, the highest odds ratios of OHCA for a 10 MUg/m3 increase in PM2.5
were observed at Lag Day 1 (1.07; 95% confidence interval (CI): 1.04-1.10), with
strong associations with advanced age (aged >=70 years) (1.09; 95% CI: 1.05-1.13)
and stroke history (1.11; 95% CI: 1.06-1.16). PM2.5-10 and NO2 also showed
significant associations with OHCAs, whereas SO2, CO, and O3 had no effects.
After simultaneously adjusting for NO2 and SO2 in a multi-pollutant model, PM2.5
remained significant. The effects of PM2.5 in the single-pollutant models for
cases with hypertension, respiratory disorders, diabetes mellitus, and heart
disease were higher than those for cases without these complications; however,
the differences were not statistically significant. The results support that
elevated PM2.5 exposure contributes to triggering OHCA, especially in those who
are advanced in age and have a history of stroke.
PMID- 28420119
TI - The Modeling and Simulation of the Galvanic Coupling Intra-Body Communication via
Handshake Channel.
AB - Intra-body communication (IBC) is a technology using the conductive properties of
the body to transmit signal, and information interaction by handshake is regarded
as one of the important applications of IBC. In this paper, a method for modeling
the galvanic coupling intra-body communication via handshake channel is proposed,
while the corresponding parameters are discussed. Meanwhile, the mathematical
model of this kind of IBC is developed. Finally, the validity of the developed
model has been verified by measurements. Moreover, its characteristics are
discussed and compared with that of the IBC via single body channel. Our results
indicate that the proposed method will lay a foundation for the theoretical
analysis and application of the IBC via handshake channel.
PMID- 28420121
TI - A 7.4 ps FPGA-Based TDC with a 1024-Unit Measurement Matrix.
AB - In this paper, a high-resolution time-to-digital converter (TDC) based on a field
programmable gate array (FPGA) device is proposed and tested. During the
implementation, a new architecture of TDC is proposed which consists of a
measurement matrix with 1024 units. The utilization of routing resources as the
delay elements distinguishes the proposed design from other existing designs,
which contributes most to the device insensitivity to variations of temperature
and voltage. Experimental results suggest that the measurement resolution is 7.4
ps, and the INL (integral nonlinearity) and DNL (differential nonlinearity) are
11.6 ps and 5.5 ps, which indicates that the proposed TDC offers high performance
among the available TDCs. Benefitting from the FPGA platform, the proposed TDC
has superiorities in easy implementation, low cost, and short development time.
PMID- 28420120
TI - Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to
Treatment Type and Line: A Retrospective Multinational Study.
AB - Acute erythroleukemia (AEL) is a rare disease typically associated with a poor
prognosis. The median survival ranges between 3-9 months from initial diagnosis.
Hypomethylating agents (HMAs) have been shown to prolong survival in patients
with myelodysplastic syndromes (MDS) and AML, but there is limited data of their
efficacy in AEL. We collected data from 210 AEL patients treated at 28
international sites. Overall survival (OS) and PFS were estimated using the
Kaplan-Meier method and the log-rank test was used for subgroup comparisons.
Survival between treatment groups was compared using the Cox proportional hazards
regression model. Eighty-eight patients were treated with HMAs, 44 front line,
and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response
rate (complete or partial) compared to first-line HMA (72% vs. 46.2%,
respectively; p <= 0.001), but similar progression-free survival (8.0 vs. 9.4
months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7
months; p = 0.564), but patients with high-risk cytogenetics treated with HMA
first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results
support the therapeutic value of HMA in AEL.
PMID- 28420122
TI - The Effect of Salt Intake and Potassium Supplementation on Serum Gastrin Levels
in Chinese Adults: A Randomized Trial.
AB - Excess dietary salt is strongly correlated with cardiovascular disease,
morbidity, and mortality. Conversely, potassium likely elicits favorable effects
against cardiovascular disorders. Gastrin, which is produced by the G-cells of
the stomach and duodenum, can increase renal sodium excretion and regulate blood
pressure by acting on the cholecystokinin B receptor. The aim of our study was to
assess the effects of altered salt and potassium supplementation on serum gastrin
levels in humans. A total of 44 subjects (38-65 years old) were selected from a
rural community in northern China. All subjects were sequentially maintained on a
relatively low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for 7
days (18.0 g/day of NaCl), and then a high-salt diet supplemented with potassium
for another 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). The high-salt intake
significantly increased serum gastrin levels (15.3 +/- 0.3 vs. 17.6 +/- 0.3
pmol/L). This phenomenon was alleviated through potassium supplementation (17.6
+/- 0.3 vs. 16.5 +/- 0.4 pmol/L). Further analyses revealed that serum gastrin
was positively correlated with 24 h urinary sodium excretion (r = 0.476, p <
0.001). By contrast, gastrin level was negatively correlated with blood pressure
in all dietary interventions (r = -0.188, p = 0.031). The present study indicated
that variations in dietary salt and potassium supplementation affected the serum
gastrin concentrations in the Chinese subjects.
PMID- 28420123
TI - Stability of Bioactive Compounds in Broccoli as Affected by Cutting Styles and
Storage Time.
AB - Broccoli contains bioactive molecules and thus its consumption is related with
the prevention of chronic and degenerative diseases. The application of wounding
stress to horticultural crops is a common practice, since it is the basis for the
fresh-cut produce industry. In this study, the effect of four different cutting
styles (CSs) (florets (CS1), florets cut into two even pieces (CS2), florets cut
into four even pieces (CS3), and florets processed into chops (CS4)) and storage
time (0 and 24 h at 20 degrees C) on the content of bioactive compounds in
broccoli was evaluated. Immediately after cutting, 5-O-caffeoylquinic acid and
caffeic acid content increased by 122.4% and 41.6% in CS4 and CS2, respectively.
Likewise, after storage, 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid
increased by 46.7% and 98.2%, respectively in CS1. Glucoerucin and
gluconasturtiin content decreased by 62% and 50%, respectively in CS3; whereas
after storage most glucosinolates increased in CS1. Total isothiocyanates,
increased by 133% immediately in CS4, and after storage CS1 showed 65% higher
levels of sulforaphane. Total ascorbic acid increased 35% after cutting in CS2,
and remained stable after storage. Results presented herein would allow broccoli
producers to select proper cutting styles that preserve or increase the content
of bioactive molecules.
PMID- 28420124
TI - Applying Broadband Dielectric Spectroscopy (BDS) for the Biophysical
Characterization of Mammalian Tissues under a Variety of Cellular Stresses.
AB - The dielectric properties of biological tissues can contribute non-invasively to
a better characterization and understanding of the structural properties and
physiology of living organisms. The question we asked, is whether these induced
changes are effected by an endogenous or exogenous cellular stress, and can they
be detected non-invasively in the form of a dielectric response, e.g., an AC
conductivity switch in the broadband frequency spectrum. This study constitutes
the first methodological approach for the detection of environmental stress
induced damage in mammalian tissues by the means of broadband dielectric
spectroscopy (BDS) at the frequencies of 1-106 Hz. Firstly, we used non-ionizing
(NIR) and ionizing radiation (IR) as a typical environmental stress.
Specifically, rats were exposed to either digital enhanced cordless
telecommunication (DECT) radio frequency electromagnetic radiation or to gamma
radiation, respectively. The other type of stress, characterized usually by high
genomic instability, was the pathophysiological state of human cancer (lung and
prostate). Analyzing the results of isothermal dielectric measurements provided
information on the tissues' water fraction. In most cases, our methodology proved
sufficient in detecting structural changes, especially in the case of IR and
malignancy. Useful specific dielectric response patterns are detected and
correlated with each type of stress. Our results point towards the development of
a dielectric-based methodology for better understanding and, in a relatively
invasive way, the biological and structural changes effected by radiation and
developing lung or prostate cancer often associated with genomic instability.
PMID- 28420125
TI - Bioavailable Citrus sinensis Extract: Polyphenolic Composition and Biological
Activity.
AB - Citrus plants contain large amounts of flavonoids with beneficial effects on
human health. In the present study, the antioxidant and anti-inflammatory
potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro
and ex vivo, using the murine macrophages cell line J774A.1 and primary
peritoneal macrophages. Following simulated gastro-intestinal digestion, the in
vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using
the human cell line Caco-2 grown as monolayers on a transwell membrane. Data
demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant
and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was
compared to the bioavailable one (CsB). Results revealed that Citrus extract were
able to reduce macrophages pro-inflammatory mediators, including nitric oxide,
iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis
polyphenols was associated with antioxidant effects, such as a reduction of
reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression.
Our results provide evidence that the bioavailable polyphenolic constituents of
the Citrussinensis extract accumulate prevalently at intestinal level and could
reach systemic circulation exerting their effect. The bioavailable fraction
showed a higher anti-inflammatory and antioxidant potential compared to the
initial extract, thus highlighting its potential nutraceutical value.
PMID- 28420126
TI - Novel Genetic Variants Associated with Child Refractory Esophageal Stricture with
Food Allergy by Exome Sequencing.
AB - BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food
allergy. Its etiology and pathogenesis are not fully understood. Identification
of novel genetic variants associated with this disease by exome sequencing (exome
seq) may provide new mechanistic insights and new therapeutic targets. METHODS:
To identify new and novel disease-associating variants, whole-exome sequencing
was performed on an Illumina NGS platform in three children with RES as well as
food allergy. RESULTS: A total of 91,024 variants were identified. By filtering
out 'normal variants' against those of the 1000 Genomes Project, we identified
12,741 remaining variants which are potentially associated with RES plus food
allergy. Among these variants, there are 11,539 single nucleotide polymorphisms
(SNPs), 627 deletions, 551 insertions and 24 mixture variants. These variants are
located in 1370 genes. They are enriched in biological processes or pathways such
as cell adhesion, digestion, receptor metabolic process, bile acid transport and
the neurological system. By the PubMatrix analysis, 50 out of the top 100 genes,
which contain most variants, have not been previously associated with any of the
17 allergy-associated diseases. These 50 genes represent newly identified allergy
associated genes. Those variants of 627 deletions and 551 insertions have also
not been reported before in RES with food allergy. CONCLUSIONS: Exome-seq is
potentially a powerful tool to identify potential new biomarkers for RES with
food allergy. This study has identified a number of novel genetic variants,
opening new avenues of research in RES plus food allergy. Additional validation
in larger and different patient populations and further exploration of the
underlying molecular mechanisms are warranted.
PMID- 28420127
TI - Glycosaminoglycan Binding and Non-Endocytic Membrane Translocation of Cell
Permeable Octaarginine Monitored by Real-Time In-Cell NMR Spectroscopy.
AB - Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the
cell surface have recently been suggested to involve in not only endocytic
cellular uptake but also non-endocytic direct cell membrane translocation of
arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive
observation and the quantitative analysis of the direct membrane translocation
processes are challenging, and the mechanism therefore remains still unresolved.
In this work, real-time in-cell NMR spectroscopy was applied to investigate the
direct membrane translocation of octaarginine (R8) into living cells. By
introducing 4-trifluoromethyl-l-phenylalanine to the N terminus of R8, the non
endocytic membrane translocation of 19F-labeled R8 (19F-R8) into a human myeloid
leukemia cell line was observed at 4 degrees C with a time resolution in the
order of minutes. 19F NMR successfully detected real-time R8 translocation: the
binding to anionic GAGs at the cell surface, followed by the penetration into the
cell membrane, and the entry into cytosol across the membrane. The NMR
concentration analysis enabled quantification of how much of R8 was staying in
the respective translocation processes with time in situ. Taken together, our in
cell NMR results provide the physicochemical rationale for spontaneous
penetration of CPPs in cell membranes.
PMID- 28420128
TI - AR Signaling and the PI3K Pathway in Prostate Cancer.
AB - Prostate cancer is a leading cause of cancer-related death in men worldwide.
Aberrant signaling in the androgen pathway is critical in the development and
progression of prostate cancer. Despite ongoing reliance on androgen receptor
(AR) signaling in castrate resistant disease, in addition to the development of
potent androgen targeting drugs, patients invariably develop treatment
resistance. Interactions between the AR and PI3K pathways may be a mechanism of
treatment resistance and inhibitors of this pathway have been developed with
variable success. Herein we outline the role of the PI3K pathway in prostate
cancer and, in particular, its association with androgen receptor signaling in
the pathogenesis and evolution of prostate cancer, as well as a review of the
clinical utility of PI3K targeting.
PMID- 28420129
TI - Hand Motion Detection in fNIRS Neuroimaging Data.
AB - As the number of people diagnosed with movement disorders is increasing, it
becomes vital to design techniques that allow the better understanding of human
brain in naturalistic settings. There are many brain imaging methods such as
fMRI, SPECT, and MEG that provide the functional information of the brain.
However, these techniques have some limitations including immobility, cost, and
motion artifacts. One of the most emerging portable brain scanners available
today is functional near-infrared spectroscopy (fNIRS). In this study, we have
conducted fNIRS neuroimaging of seven healthy subjects while they were performing
wrist tasks such as flipping their hand with the periods of rest (no movement).
Different models of support vector machine is applied to these fNIRS neuroimaging
data and the results show that we could classify the action and rest periods with
the accuracy of over 80% for the fNIRS data of individual participants. Our
results are promising and suggest that the presented classification method for
fNIRS could further be applied to real-time applications such as brain computer
interfacing (BCI), and into the future steps of this research to record brain
activity from fNIRS and EEG, and fuse them with the body motion sensors to
correlate the activities.
PMID- 28420130
TI - Gaseous Elemental Mercury and Total and Leached Mercury in Building Materials
from the Former Hg-Mining Area of Abbadia San Salvatore (Central Italy).
AB - Mercury has a strong environmental impact since both its organic and inorganic
forms are toxic, and it represents a pollutant of global concern. Liquid Hg is
highly volatile and can be released during natural and anthropogenic processes in
the hydrosphere, biosphere and atmosphere. In this study, the distribution of
Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations
on paint, plaster, roof tiles, concrete, metals, dust and wood structures were
determined in the main buildings and structures of the former Hg-mining area of
Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into
seven units) covers a surface of about 65 ha and contains mining structures and
managers' and workers' buildings. Nine surveys of GEM measurements were carried
out from July 2011 to August 2015 for the buildings and structures located in
Units 2, 3 and 6, the latter being the area where liquid mercury was produced.
Measurements were also performed in February, April, July, September and December
2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a
strong variability in time and space mostly depending on ambient temperature and
the operational activities that were carried out in each building. The Unit 2
surveys carried out in the hotter period (from June to September) showed GEM
concentrations up to 27,500 ng.m-3, while in Unit 6, they were on average much
higher, and occasionally, they saturated the GEM measurement device (>50,000 ng.m
3). Concentrations of total (in mg.kg-1) and leached (in MUg.L-1) mercury
measured in different building materials (up to 46,580 mg.kg-1 and 4470 mg.L-1,
respectively) were highly variable, being related to the edifice or mining
structure from which they were collected. The results obtained in this study are
of relevant interest for operational cleanings to be carried out during
reclamation activities.
PMID- 28420132
TI - A Smart Voltage and Current Monitoring System for Three Phase Inverters Using an
Android Smartphone Application.
AB - In this paper, a new smart voltage and current monitoring system (SVCMS)
technique is proposed. It monitors a three phase electrical system using an
Arduino platform as a microcontroller to read the voltage and current from
sensors and then wirelessly send the measured data to monitor the results using a
new Android application. The integrated SVCMS design uses an Arduino Nano V3.0 as
the microcontroller to measure the results from three voltage and three current
sensors and then send this data, after calculation, to the Android smartphone
device of an end user using Bluetooth HC-05. The Arduino Nano V3.0 controller and
Bluetooth HC-05 are a cheap microcontroller and wireless device, respectively.
The new Android smartphone application that monitors the voltage and current
measurements uses the open source MIT App Inventor 2 software. It allows for
monitoring some elementary fundamental voltage power quality properties. An
effort has been made to investigate what is possible using available off-the
shelf components and open source software.
PMID- 28420131
TI - Work Characteristics Associated with Physical Functioning in Women.
AB - Women make up almost half of the labor force with older women becoming a growing
segment of the population. Work characteristics influence physical functioning
and women are at particular risk for physical limitations. However, little
research has explored the effects of work characteristics on women's physical
functioning. U.S. women between the ages of 50 and 79 were enrolled in the
Women's Health Initiative Observational Study between 1993 and 1998. Women
provided job titles and years worked at their three longest-held jobs (n =
79,147). Jobs were linked to characteristics in the Occupational Information
Network. Three categories of job characteristics related to substantive
complexity, physical demand, and social collaboration emerged. The association
between job characteristics and physical limitations in later life, measured
using a SF-36 Physical Functioning score <25th percentile, was examined using
modified Poisson regression. After controlling for confounding variables, high
physical demand was positively associated with physical limitations (RR = 1.09
CI: 1.06-1.12) and substantively complex work was negatively associated (RR =
0.94, CI: 0.91-0.96). Jobs requiring complex problem solving, active learning,
and critical thinking were associated with better physical functioning. Employers
should explore opportunities to reduce strain from physically demanding jobs and
incorporate substantively complex tasks into women's work to improve long-term
health.
PMID- 28420133
TI - Using Dimensionality Reduction Techniques for Refining Passive Indoor Positioning
Systems Based on Radio Fingerprinting.
AB - Indoor positioning methods based on fingerprinting and radio signals rely on the
quality of the radio map. For example, for room-level classification purposes, it
is required that the signal observations related to each room exhibit significant
differences in their RSSI values. However, it is difficult to verify and
visualize that separability since radio maps are constituted by multi-dimensional
observations whose dimension is directly related to the number of access points
or monitors being employed for localization purposes. In this paper, we propose a
refinement cycle for passive indoor positioning systems, which is based on
dimensionality reduction techniques, to evaluate the quality of a radio map. By
means of these techniques and our own data representation, we have defined two
different visualization methods to obtain graphical information about the quality
of a particular radio map in terms of overlapping areas and outliers. That
information will be useful to determine whether new monitors are required or some
existing ones should be moved. We have performed an exhaustive experimental
analysis based on a variety of different scenarios, some deployed by our own
research group and others corresponding to a well-known existing dataset widely
analyzed by the community, in order to validate our proposal. As we will show,
among the different combinations of data representation methods and
dimensionality reduction techniques that we discuss, we have found that there are
some specific configurations that are more useful in order to perform the
refinement process.
PMID- 28420134
TI - Visual Detection and Tracking System for a Spherical Amphibious Robot.
AB - With the goal of supporting close-range observation tasks of a spherical
amphibious robot, such as ecological observations and intelligent surveillance, a
moving target detection and tracking system was designed and implemented in this
study. Given the restrictions presented by the amphibious environment and the
small-sized spherical amphibious robot, an industrial camera and vision
algorithms using adaptive appearance models were adopted to construct the
proposed system. To handle the problem of light scattering and absorption in the
underwater environment, the multi-scale retinex with color restoration algorithm
was used for image enhancement. Given the environmental disturbances in practical
amphibious scenarios, the Gaussian mixture model was used to detect moving
targets entering the field of view of the robot. A fast compressive tracker with
a Kalman prediction mechanism was used to track the specified target. Considering
the limited load space and the unique mechanical structure of the robot, the
proposed vision system was fabricated with a low power system-on-chip using an
asymmetric and heterogeneous computing architecture. Experimental results
confirmed the validity and high efficiency of the proposed system. The design
presented in this paper is able to meet future demands of spherical amphibious
robots in biological monitoring and multi-robot cooperation.
PMID- 28420135
TI - A Prosthetic Hand Body Area Controller Based on Efficient Pattern Recognition
Control Strategies.
AB - Poliarticulated prosthetic hands represent a powerful tool to restore
functionality and improve quality of life for upper limb amputees. Such devices
offer, on the same wearable node, sensing and actuation capabilities, which are
not equally supported by natural interaction and control strategies. The control
in state-of-the-art solutions is still performed mainly through complex encoding
of gestures in bursts of contractions of the residual forearm muscles, resulting
in a non-intuitive Human-Machine Interface (HMI). Recent research efforts explore
the use of myoelectric gesture recognition for innovative interaction solutions,
however there persists a considerable gap between research evaluation and
implementation into successful complete systems. In this paper, we present the
design of a wearable prosthetic hand controller, based on intuitive gesture
recognition and a custom control strategy. The wearable node directly actuates a
poliarticulated hand and wirelessly interacts with a personal gateway (i.e., a
smartphone) for the training and personalization of the recognition algorithm.
Through the whole system development, we address the challenge of integrating an
efficient embedded gesture classifier with a control strategy tailored for an
intuitive interaction between the user and the prosthesis. We demonstrate that
this combined approach outperforms systems based on mere pattern recognition,
since they target the accuracy of a classification algorithm rather than the
control of a gesture. The system was fully implemented, tested on healthy and
amputee subjects and compared against benchmark repositories. The proposed
approach achieves an error rate of 1.6% in the end-to-end real time control of
commonly used hand gestures, while complying with the power and performance
budget of a low-cost microcontroller.
PMID- 28420136
TI - Discovery of an Octahedral Silicon Complex as a Potent Antifungal Agent.
AB - Octahedral transition metal complexes have been shown to have tremendous
applications in chemical biology and medicinal chemistry. Meanwhile, structural
transition metals can be replaced by inert octahedral silicon in a proof-of
principle study. We here introduce the first example of octahedral silicon
complexes, which can very well serve as an efficient antimicrobial agent. The
typical silicon arenediolate complex 1 {[(phen)2Si(OO)](PF6)2, with phen = 1,10
phenanthroline, OO = 9,10-phenanthrenediolate} exhibited significant inhibition
towards the growth of Cryptococcus neoformans with MIC and MFC values of 4.5 and
11.3 MUM, respectively. Moreover, it was fungicidal against both proliferative
and quiescent Cryptococcus cells. This work may set the stage for the development
of novel antifungal drugs based upon hexacoodinate silicon scaffolds.
PMID- 28420137
TI - Modification of the Mycotoxin Deoxynivalenol Using Microorganisms Isolated from
Environmental Samples.
AB - The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of
wheat, barley, and maize. New strategies are needed to reduce or eliminate DON in
feed and food products. Microorganisms from plant and soil samples collected in
Blacksburg, VA, USA, were screened by incubation in a mineral salt media
containing 100 MUg/mL DON and analysis by gas chromatography mass spectrometry
(GC/MS). Two mixed cultures derived from soil samples consistently decreased DON
levels in assays using DON as the sole carbon source. Nuclear magnetic resonance
(NMR) analysis indicated that 3-keto-4-deoxynivalenol was the major by-product of
DON. Via 16S rRNA sequencing, these mixed cultures, including mostly members of
the genera Acinetobacter, Leadbetterella, and Gemmata, were revealed. Incubation
of one of these mixed cultures with wheat samples naturally contaminated with 7.1
MUg/mL DON indicated nearly complete conversion of DON to the less toxic 3-epimer
DON (3-epi-DON). Our work extends previous studies that have demonstrated the
potential for bioprospecting for microorganisms from the environment to remediate
or modify mycotoxins for commercial applications, such as the reduction of
mycotoxins in fuel ethanol co-products.
PMID- 28420138
TI - Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis
Induced Cardiac Dysfunction.
AB - Cardiac dysfunction, in particular of the left ventricle, is a common and early
event in sepsis, and is strongly associated with an increase in patients'
mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and
transient generation of the lipid mediator ceramide-is involved in both the
regulation of host response in sepsis as well as in the pathogenesis of chronic
heart failure. This study determined the degree and the potential role to which
SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both
genetically deficient and pharmacologically-treated animals in a polymicrobial
sepsis model. As surrogate parameters of sepsis-induced cardiomyopathy, cardiac
function, markers of oxidative stress as well as troponin I levels were found to
be improved in desipramine-treated animals, desipramine being an inhibitor of
ceramide formation. Additionally, ceramide formation in cardiac tissue was
dysregulated in SMPD1+/+ as well as SMPD1-/- animals, whereas desipramine
pretreatment resulted in stable, but increased ceramide content during host
response. This was a result of elevated de novo synthesis. Strikingly,
desipramine treatment led to significantly improved levels of surrogate markers.
Furthermore, similar results in desipramine-pretreated SMPD1-/- littermates
suggest an SMPD1-independent pathway. Finally, a pattern of differentially
expressed transcripts important for regulation of apoptosis as well as
antioxidative and cytokine response supports the concept that desipramine
modulates ceramide formation, resulting in beneficial myocardial effects. We
describe a novel, protective role of desipramine during sepsis-induced cardiac
dysfunction that controls ceramide content. In addition, it may be possible to
modulate cardiac function during host response by pre-conditioning with the Food
and Drug Administration (FDA)-approved drug desipramine.
PMID- 28420139
TI - Interplay between Oxidative Stress and Nutrient Sensing Signaling in the
Developmental Origins of Cardiovascular Disease.
AB - Cardiovascular disease (CVD) presents a global health burden, despite recent
advances in management. CVD can originate from early life by so-called
"developmental origins of health and disease" (DOHaD). Epidemiological and
experimental evidence supports that early-life insults can induce programming of
later CVD. Underlying the DOHaD concept, early intervention may offset
programming process to prevent the development of CVD, namely reprogramming.
Oxidative stress and nutrient sensing signals have been considered to be major
mechanisms of cardiovascular programming, while the interplay between these two
mechanisms have not been examined in detail. This review summarizes current
evidence that supports the link between oxidative stress and nutrient sensing
signaling to cardiovascular programming, with an emphasis on the l-arginine
asymmetric dimethylarginine (ADMA)-nitric oxide (NO) pathway. This review
provides an overview of evidence from human studies supporting fetal programming
of CVD, insight from animal models of cardiovascular programming and oxidative
stress, impact of the l-arginine-ADMA-NO pathway in cardiovascular programming,
the crosstalk between l-arginine metabolism and nutrient sensing signals, and
application of reprogramming interventions to prevent the programming of CVD. A
greater understanding of the mechanisms underlying cardiovascular programming is
essential to developing early reprogramming interventions to combat the globally
growing epidemic of CVD.
PMID- 28420140
TI - Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and
Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis
Patients.
AB - Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its
antioxidant and anti-inflammatory activities have been demonstrated in in vitro
and in vivo animal models. The aim of this study was to investigate the activity
of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies
obtained during colonoscopy from 14 patients with active UC were immediately
placed in an organ culture chamber and challenged with lipopolysaccharide from
Escherichia coli (EC-LPS) at 1 MUg/mL in the presence or absence of 3 mM OLE. The
expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in
total protein extracts from treated colonic biopsies by Western blotting. Levels
of IL-17 were also measured in culture supernatant by ELISA. A microscopic
evaluation of the cultured biopsies was performed by conventional histology and
immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower
in samples treated with OLE + EC-LPS compared with those treated with EC-LPS
alone (0.80 +/- 0.15 arbitrary units (a.u.) vs. 1.06 +/- 0.19 a.u., p = 0.003,
and 0.71 +/- 0.08 a.u. vs. 1.26 +/- 0.42 a.u., p = 0.03, respectively) as were
the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic
samples (21.16 +/- 8.64 pg/mL vs. 40.67 +/- 9.24 pg/mL, p = 0.01).
Histologically, OLE-treated colonic samples showed an amelioration of
inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while
CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in
colonic biopsies from UC patients. These new data support a potential role of OLE
in the treatment of UC.
PMID- 28420142
TI - Cross-Spectral Local Descriptors via Quadruplet Network.
AB - This paper presents a novel CNN-based architecture, referred to as Q-Net, to
learn local feature descriptors that are useful for matching image patches from
two different spectral bands. Given correctly matched and non-matching cross
spectral image pairs, a quadruplet network is trained to map input image patches
to a common Euclidean space, regardless of the input spectral band. Our approach
is inspired by the recent success of triplet networks in the visible spectrum,
but adapted for cross-spectral scenarios, where, for each matching pair, there
are always two possible non-matching patches: one for each spectrum. Experimental
evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed
approach improves the state-of-the-art. Moreover, the proposed technique can also
be used in mono-spectral settings, obtaining a similar performance to triplet
network descriptors, but requiring less training data.
PMID- 28420141
TI - Coordinated Actions of MicroRNAs with other Epigenetic Factors Regulate Skeletal
Muscle Development and Adaptation.
AB - Epigenetics plays a pivotal role in regulating gene expression in development, in
response to cellular stress or in disease states, in virtually all cell types.
MicroRNAs (miRNAs) are short, non-coding RNA molecules that mediate RNA silencing
and regulate gene expression. miRNAs were discovered in 1993 and have been
extensively studied ever since. They can be expressed in a tissue-specific manner
and play a crucial role in tissue development and many biological processes.
miRNAs are responsible for changes in the cell epigenome because of their ability
to modulate gene expression post-transcriptionally. Recently, numerous studies
have shown that miRNAs and other epigenetic factors can regulate each other or
cooperate in regulating several biological processes. On the one hand, the
expression of some miRNAs is silenced by DNA methylation, and histone
modifications have been demonstrated to modulate miRNA expression in many cell
types or disease states. On the other hand, miRNAs can directly target epigenetic
factors, such as DNA methyltransferases or histone deacetylases, thus regulating
chromatin structure. Moreover, several studies have reported coordinated actions
between miRNAs and other epigenetic mechanisms to reinforce the regulation of
gene expression. This paper reviews multiple interactions between miRNAs and
epigenetic factors in skeletal muscle development and in response to stimuli or
disease.
PMID- 28420143
TI - Biotinylated Chlorin and Its Zinc and Indium Complexes: Synthesis and In Vitro
Biological Evaluation for Photodynamic Therapy.
AB - The synthesis and characterization of biotinylated chlorin photosensitizer and
the corresponding zinc and indium complexes are described for potential
applications in photodynamic therapy (PDT) for cancer. Phototoxicity of the
biotin-chlorin conjugate and the metallated complexes was determined in colon
carcinoma CT26 cell lines known to overexpress biotin (Vit B7) receptors. Cell
survival assay indicated that the biotinylated chlorin and indium complex showed
increased cell growth inhibition than the zinc complex and the starting chlorin
(methyl pheophorbide). Fluorescence microcopy studies revealed the generation of
apoptotic cells upon light irradiation of colon cells treated with the indium
complex. Targeting biotin receptors in cancer cells can improve specificity of
photosensitizers for PDT applications.
PMID- 28420144
TI - Retinoids Regulate Adipogenesis Involving the TGFbeta/SMAD and Wnt/beta-Catenin
Pathways in Human Bone Marrow Mesenchymal Stem Cells.
AB - Retinoids may regulate cell differentiation as ligands of retinoic acid receptors
(RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted
adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein
beta (C/EBPbeta) in the early stages, but blocked adipogenesis at a later stage
in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted
adipogenesis at all time points in hBMSCs. The effect of RAR agonists was
mediated mainly by the RARbeta subtype. RAR agonists, in contrast to RXR
agonists, significantly promoted the expression of RARbeta. Knockdown of the
RARbeta gene via small hairpin RNA (shRNA) attenuated the inhibition of RAR
agonists toward adipogenesis. Furthermore, we found that RAR agonists upregulated
the transforming growth factor beta (TGFbeta)/SMAD pathway and Wnt/beta-catenin
pathway on adipogenesis in hBMSCs, and the stimulating effects were noticeably
decreased with the RARbeta gene knockdown. Both RAR agonists and RXR agonists
inhibited adipogenesis and blocked the promoter activity of C/EBPbeta and
peroxisome proliferator-activated receptor gamma (PPARgamma) in SW872 cell. These
results indicated the RAR agonists perform dual roles in adipogenesis in hBMSCs,
and the TGFbeta/SMAD pathway and Wnt/beta-catenin pathway may involve the
inhibitory effect of RAR agonists. RARbeta is the main receptor subtype mediating
the effect. The roles of RXR agonists in adipogenesis exhibited cell type
specific differences, and may be based on the integration of signals from
different RXR dimers.
PMID- 28420145
TI - Evaluation of Polyphenolic Content, Antioxidant and Diuretic Activities of Six
Fumaria Species.
AB - Romanian traditional medicine describes the use of aerial parts of Fumaria
species to treat hepatobiliary diseases as well as diuretic agents. The present
study aims to investigate the chemical composition, antioxidant properties, and
diuretic effects of several Fumaria species. LC/MS analysis revealed that Fumaria
species contain phenolic acids and high amounts of flavonoids with rutin and
isoquercitrin as main compounds. Concerning antioxidant capacity, the most
significant results were obtained for F. capreolata and F. vailantii. Both
species showed a good correlation between the antioxidant capacity and a high
amount of flavonoids. Furthermore, the extracts of F. officinalis and F.
schleicheri produced a strong increase in urinary volumetric excretion of saline
loaded rats, 24 h after the oral administration of a single dose of 250 mg/kg bw.
Moreover, both extracts of F. officinalis and F. schleicheri increased the
urinary excretion of Na+ and K+. Results from the present study offer a new
perspective concerning the chemical composition and bioactivities of
traditionally used fumitory species.
PMID- 28420146
TI - Optimization of Ultrasound-Assisted Extraction of Antioxidants from the Mung Bean
Coat.
AB - Mung bean (Vigna radiata) sprout is commonly consumed as a vegetable, while the
coat of the germinated mung bean is a waste. In this paper, an ultrasound
assisted extraction method has been developed to extract natural antioxidants
from the seed coat of mung bean. Several experimental parameters-which included
ethanol concentration, solvent/material ratio, ultrasound extraction time,
temperature, and power-were studied in single-factor experiments. The interaction
of three key experimental parameters (ethanol concentration, solvent/material
ratio, and ultrasonic extraction time) was further investigated by response
surface method. Besides, traditional extracting methods, including maceration and
Soxhlet extraction methods, were also carried out for comparison. The results
suggested that the best extracting condition was 37.6% (v/v) of ethanol
concentration, 35.1:1 mL/g of solvent/material ratio and ultrasonic extraction of
46.1 min at 70 degrees C under 500 W ultrasonic irradiation. The antioxidant
capacity (178.28 +/- 7.39 umol Trolox/g DW) was much stronger than those obtained
by the maceration extraction process (158.66 +/- 4.73 umol Trolox/g DW) and the
Soxhlet extraction process (138.42 +/- 3.63 umol Trolox/g DW). In addition,
several antioxidant components in the extract were identified and quantified.
This study is helpful for value-added utilization of the waste from germinated
mung bean.
PMID- 28420147
TI - Intake Levels of Fish in the UK Paediatric Population.
AB - The United Kingdom (UK) is an island and its culture, including diet, is heavily
influenced by the maritime resources. Dietary guidance in the UK recommends
intake of fish, which provides important nutrients, such as long-chain omega-3
polyunsaturated fatty acids (n-3 PUFA). This study was designed to describe the
fish intake habits of UK children using a nationally representative sample.
Dietary and socio-demographic data of children 2-18 (N = 2096) in the National
Diet and Nutrition Survey Rolling Program (NDNS) Years 1-4 (2008-2012) were
extracted. Average nutrient and food intakes were estimated. Logistic regression
models were used to predict the meeting of fish intake recommendations,
controlling for age, sex, income, total energy intake, and survey year. All
analyses were conducted using survey routines and dietary survey weights. In this
nationally representative study, 4.7% of children met the fish and 4.5% the oily
fish intake recommendations; only 1.3% of the population met both
recommendations. Fish intake levels did not significantly change with children's
increasing age. Higher vegetable but lower meat consumption predicted meeting the
fish intake recommendations, indicating that children eating fish have better
diet quality than non-consumers. Further research is needed to explore how intake
behaviours can be changed to improve children's diet quality.
PMID- 28420149
TI - Advanced Stage at Presentation Remains a Major Factor Contributing to Breast
Cancer Survival Disparity between Public and Private Hospitals in a Middle-Income
Country.
AB - Background: Survival disparities in cancer are known to occur between public and
private hospitals. We compared breast cancer presentation, treatment and survival
between a public academic hospital and a private hospital in a middle-income
country. Methods: The demographics, clinical characteristics, treatment and
overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed
between 2001 and 2011 in the public hospital were compared with 1199 patients
from the private hospital. Results: Compared to patients in the private hospital,
patients from the public hospital were older at presentation, and had more
advanced cancer stages. They were also more likely to receive mastectomy and
chemotherapy but less radiotherapy. The five-year OS in public patients was
significantly lower than in private patients (71.6% vs. 86.8%). This difference
was largely attributed to discrepancies in stage at diagnosis and, although to a
much smaller extent, to demographic differences and treatment disparities. Even
following adjustment for these factors, patients in the public hospital remained
at increased risk of mortality compared to their counterparts in the private
hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36-1.85). Conclusion:
Late stage at diagnosis appears to be a major contributing factor explaining the
breast cancer survival disparity between public and private patients in this
middle-income setting.
PMID- 28420148
TI - Differential Effect of Sucrose and Fructose in Combination with a High Fat Diet
on Intestinal Microbiota and Kidney Oxidative Stress.
AB - There is controversial information about the adverse effect of sucrose (S) or
fructose (F) in the development of obesity. Thus, the purpose of the study was to
evaluate the effect of S or F in a high fat diet (HF) on gut microbiota and renal
oxidative stress. Rats were fed for four months with either high-fat + sucrose
(HFS) or high-fat + fructose (HFF) or a control diet (C). Half of the HFS or HFF
groups were maintained with the same diet and the other half were switched to the
consumption of C. HFS and HFF groups increased 51% and 19% body weight,
respectively, compared with the C group. Body fat mass, metabolic inflexibility,
glucose intolerance, lipopolysaccharide (LPS), insulin, renal reactive oxygen
species (ROS), malondialdehyde (MDA), Nadphox, and Srebp-1 were significantly
higher and antioxidant enzymes and lean body mass were significantly lower in the
HFS group with respect to the HF-F group. Change in the consumption of HFS or HFF
to a C diet ameliorated the insulin and glucose intolerance. The type of
carbohydrate differentially modified the microbiota composition, however, both
groups significantly decreased C. eutactus with respect to the C group. Thus,
metabolic alterations with the HFS diet had a more detrimental effect than HFF.
PMID- 28420151
TI - Out-of-Plane Continuous Electrostatic Micro-Power Generators.
AB - This paper presents an out-of-plane electrostatic micro-power generator (MPG).
Electret-based continuous MPGs with different gaps and masses are fabricated to
demonstrate the merits of this topology. Experimental results of the MPG
demonstrate output power of 1 mW for a base acceleration amplitude and frequency
of 0.08 g and 86 Hz. The MPGs also demonstrate a wideband harvesting bandwidth
reaching up to 9 Hz. A free-flight and an impact mode model of electrostatic MPGs
are also derived and validated by comparison to experimental results.
PMID- 28420152
TI - Measurement of Pressure Fluctuations inside a Model Thrust Bearing Using PVDF
Sensors.
AB - Thrust bearings play a vital role in propulsion systems. They rely on a thin
layer of oil being trapped between rotating surfaces to produce a low friction
interface. The "quality" of this bearing affects many things from noise
transmission to the ultimate catastrophic failure of the bearing itself. As a
result, the direct measure of the forces and vibrations within the oil filled
interface would be very desirable and would give an indication of the condition
of the bearing in situ. The thickness of the oil film is, however, very small and
conventional vibration sensors are too cumbersome to use in this confined space.
This paper solves this problem by using a piezoelectric polymer film made from
Polyvinylidine Fluoride (PVDF). These films are very thin (50 m) and flexible and
easy to install in awkward spaces such as the inside of a thrust bearing. A model
thrust bearing was constructed using a 3D printer and PVDF films inserted into
the base of the bearing. In doing so, it was possible to directly measure the
force fluctuations due to the rotating pads and investigate various properties of
the thrust bearing itself.
PMID- 28420150
TI - Virtual Reality for Research in Social Neuroscience.
AB - The emergence of social neuroscience has significantly advanced our understanding
of the relationship that exists between social processes and their
neurobiological underpinnings. Social neuroscience research often involves the
use of simple and static stimuli lacking many of the potentially important
aspects of real world activities and social interactions. Whilst this research
has merit, there is a growing interest in the presentation of dynamic stimuli in
a manner that allows researchers to assess the integrative processes carried out
by perceivers over time. Herein, we discuss the potential of virtual reality for
enhancing ecological validity while maintaining experimental control in social
neuroscience research. Virtual reality is a technology that allows for the
creation of fully interactive, three-dimensional computerized models of social
situations that can be fully controlled by the experimenter. Furthermore, the
introduction of interactive virtual characters-either driven by a human or by a
computer-allows the researcher to test, in a systematic and independent manner,
the effects of various social cues. We first introduce key technical features and
concepts related to virtual reality. Next, we discuss the potential of this
technology for enhancing social neuroscience protocols, drawing on illustrative
experiments from the literature.
PMID- 28420153
TI - Health-Related Quality of Life of the General German Population in 2015: Results
from the EQ-5D-5L.
AB - The EQ-5D-5L is a widely used generic instrument to measure health-related
quality of life. This study evaluates health perception in a representative
sample of the general German population from 2015. To compare results over time,
a component analysis technique was used that separates changes in the description
and valuation of health states. The whole sample and also subgroups, stratified
by sociodemographic parameters as well as disease affliction, were analyzed. In
total, 2040 questionnaires (48.4% male, mean age 47.3 year) were included. The
dimension with the lowest number of reported problems was self-care (93.0%
without problems), and the dimension with the highest proportion of impairment
was pain/discomfort (71.2% without problems). Some 64.3% of the study population
were identified as problem-free. The visual analog scale (VAS) mean for all
participants was 85.1. Low education was connected with significantly lower VAS
scores, but the effect was small. Depression, heart disease, and diabetes had a
strong significant negative effect on reported VAS means. Results were slightly
better than those in a similar 2012 survey; the most important driver was the
increase in the share of the study population that reported to be problem-free.
In international comparisons, health perception of the general German population
is relatively high and, compared with previous German studies, fairly stable over
recent years. Elderly and sick people continue to report significant reductions
in perceived health states.
PMID- 28420155
TI - New Compact 3-Dimensional Shape Descriptor for a Depth Camera in Indoor
Environments.
AB - This study questions why existing local shape descriptors have high
dimensionalities (up to hundreds) despite simplicity of local shapes. We derived
an answer from a historical context and provided an alternative solution by
proposing a new compact descriptor. Although existing descriptors can express
complicated shapes and depth sensors have been improved, complex shapes are
rarely observed in an ordinary environment and a depth sensor only captures a
single side of a surface with noise. Therefore, we designed a new descriptor
based on principal curvatures, which is compact but practically useful. For
verification, the CoRBS dataset, the RGB-D Scenes dataset and the RGB-D Object
dataset were used to compare the proposed descriptor with existing descriptors in
terms of shape, instance, and category recognition rate. The proposed descriptor
showed a comparable performance with existing descriptors despite its low
dimensionality of 4.
PMID- 28420154
TI - Mechanisms of LTR-Retroelement Transposition: Lessons from Drosophila
melanogaster.
AB - Long terminal repeat (LTR) retrotransposons occupy a special place among all
mobile genetic element families. The structure of LTR retrotransposons that have
three open reading frames is identical to DNA forms of retroviruses that are
integrated into the host genome. Several lines of evidence suggest that LTR
retrotransposons share a common ancestry with retroviruses and thus are highly
relevant to understanding mechanisms of transposition. Drosophila melanogaster is
an exceptionally convenient model for studying the mechanisms of retrotransposon
movement because many such elements in its genome are transpositionally active.
Moreover, two LTRretrotransposons of D. melanogaster, gypsy and ZAM, have been
found to have infectious properties and have been classified as errantiviruses.
Despite numerous studies focusing on retroviral integration process, there is
still no clear understanding of integration specificity in a target site. Most
LTR retrotransposons non-specifically integrate into a target site. Site
specificity of integration at vertebrate retroviruses is rather relative. At the
same time, sequence-specific integration is the exclusive property of
errantiviruses and their derivatives with two open reading frames. The possible
basis for the errantivirus integration specificity is discussed in the present
review.
PMID- 28420156
TI - A Strain-Based Method to Estimate Slip Angle and Tire Working Conditions for
Intelligent Tires Using Fuzzy Logic.
AB - Tires equipped with sensors, the so-called "intelligent tires", can provide vital
information for control systems, drivers and external users. In this research,
tire dynamic strain characteristics in cornering conditions are collected and
analysed in relation to the variation of tire working conditions, such as
inflation pressure, rolling speed, vertical load and slip angle. An experimental
tire strain-based prototype and an indoor tire test rig are used to demonstrate
the suitability of strain sensors to establish relations between strain data and
lateral force. The results of experiments show that strain values drop sharply
when lateral force is decreasing, which can be used to predict tire slip
conditions. As a first approach to estimate some tire working conditions, such as
the slip angle and vertical load, a fuzzy logic method has been developed. The
simulation and test results confirm the feasibility of strain sensors and the
proposed computational model to solve the non-linearity characteristics of the
tires' parameters and turn tires into a source of useful information.
PMID- 28420157
TI - The Effects of PM2.5 from Asian Dust Storms on Emergency Room Visits for
Cardiovascular and Respiratory Diseases.
AB - A case-crossover study examined how PM2.5 from Asian Dust Storms (ADS) affects
the number of emergency room (ER) admissions for cardiovascular diseases (CVDs)
and respiratory diseases (RDs). Our data indicated that PM2.5 concentration from
ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR)
increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per 10 ug/m3
increase in PM2.5 levels, for CVDs and RDs, respectively. A 10 ug/m3 increase in
PM2.5 from ADSs was significantly associated with an increase in ER visits for
CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for
females (an increase of 3.09 in OR). In contrast, PM2.5 levels had a significant
impact on RD ER visits among those under 65 years of age (OR = 1.77). The risk of
ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the
day after (lag 0 and lag 1); the corresponding risk increase for RDs only
increased on the fifth day after the ADS (lag 5). In Taiwan's late winter and
spring, the severity of ER visits for CVDs and RDs increases. Environmental
protection agencies should employ an early warning system for ADS to reduce high
risk groups' exposure to PM2.5.
PMID- 28420158
TI - Intelligent Medical Garments with Graphene-Functionalized Smart-Cloth ECG
Sensors.
AB - Biopotential signals are recorded mostly by using sticky, pre-gelled electrodes,
which are not ideal for wearable, point-of-care monitoring where the usability of
the personalized medical device depends critically on the level of comfort and
wearability of the electrodes. We report a fully-wearable medical garment for
mobile monitoring of cardiac biopotentials from the wrists or the neck with
minimum restriction to regular clothing habits. The wearable prototype is based
on elastic bands with graphene functionalized, textile electrodes and battery
powered, low-cost electronics for signal acquisition and wireless transmission.
Comparison of the electrocardiogram (ECG) recordings obtained from the wearable
prototype against conventional wet electrodes indicate excellent conformity and
spectral coherence among the two signals.
PMID- 28420159
TI - Expeditious Synthesis of Dianionic-Headed 4-Sulfoalkanoic Acid Surfactants.
AB - 4-Sulfoalkanoic acids are a class of important dianionic-headed surfactants.
Various 4-sulfoalkanoic acids with straight C8, C10, C12, C14, C16, and C18
chains were synthesized expeditiously through the radical addition of methyl 2
((ethoxycarbonothioyl)thio)acetate to linear terminal olefins and subsequent
oxidation with peroxyformic acid. This is a useful and convenient strategy for
the synthesis of dianionic-headed surfactants with a carboxylic acid and sulfonic
acid functionalities in the head group region.
PMID- 28420160
TI - Global Transmission Dynamics of Measles in the Measles Elimination Era.
AB - Although there have been many epidemiological reports of the inter-country
transmission of measles, systematic analysis of the global transmission dynamics
of the measles virus (MV) is limited. In this study, we applied phylogeographic
analysis to characterize the global transmission dynamics of the MV using large
scale genetic sequence data (obtained for 7456 sequences) from 115 countries
between 1954 and 2015. These analyses reveal the spatial and temporal
characteristics of global transmission of the virus, especially in Australia,
China, India, Japan, the UK, and the USA in the period since 1990. The
transmission is frequently observed, not only within the same region but also
among distant and frequently visited areas. Frequencies of export from measles
endemic countries, such as China, India, and Japan are high but decreasing, while
the frequencies from countries where measles is no longer endemic, such as
Australia, the UK, and the USA, are low but slightly increasing. The world is
heading toward measles eradication, but the disease is still transmitted
regionally and globally. Our analysis reveals that countries wherein measles is
endemic and those having eliminated the disease (apart from occasional outbreaks)
both remain a source of global transmission in this measles elimination era. It
is therefore crucial to maintain vigilance in efforts to monitor and eradicate
measles globally.
PMID- 28420161
TI - MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad.
AB - Deregulation of MYC family proteins in cancer is associated with a global
reprogramming of gene expression, ultimately promoting glycolytic pathways, cell
growth, and proliferation. It is well known that MYC upregulation triggers cell
autonomous apoptosis in normal tissues, while frankly malignant cells develop
resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as
inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell
autonomous apoptotic death through an evolutionarily conserved mechanism known as
"cell competition". With regard to this intimate and dual relationship between
MYC and cell death, recent evidence obtained in Drosophila models of cancer has
revealed that, in early tumourigenesis, MYC upregulation guides the clonal
expansion of mutant cells, while the surrounding tissue undergoes non-cell
autonomous death. Apoptosis inhibition in this context was shown to restrain
tumour growth and to restore a wild-type phenotype. This suggests that cell
autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may
shape tumour growth in different ways, soliciting the need to reconsider the role
of cell death in cancer in the light of this new level of complexity. Here we
review recent literature about MYC and cell competition obtained in Drosophila,
with a particular emphasis on the relevance of cell death to cell competition
and, more generally, to cancer. Possible implications of these findings for the
understanding of mammalian cancers are also discussed.
PMID- 28420162
TI - Hepatocyte Growth Factor, a Key Tumor-Promoting Factor in the Tumor
Microenvironment.
AB - The tumor microenvironment plays a key role in tumor development and progression.
Stromal cells secrete growth factors, cytokines and extracellular matrix proteins
which promote growth, survival and metastatic spread of cancer cells. Fibroblasts
are the predominant constituent of the tumor stroma and Hepatocyte Growth Factor
(HGF), the specific ligand for the tyrosine kinase receptor c-MET, is a major
component of their secretome. Indeed, cancer-associated fibroblasts have been
shown to promote growth, survival and migration of cancer cells in an HGF
dependent manner. Fibroblasts also confer resistance to anti-cancer therapy
through HGF-induced epithelial mesenchymal transition (EMT) and activation of pro
survival signaling pathways such as ERK and AKT in tumor cells. Constitutive
HGF/MET signaling in cancer cells is associated with increased tumor
aggressiveness and predicts poor outcome in cancer patients. Due to its role in
tumor progression and therapeutic resistance, both HGF and MET have emerged as
valid therapeutic targets. Several inhibitors of MET and HGF are currently being
tested in clinical trials. Preclinical data provide a strong indication that
inhibitors of HGF/MET signaling overcome both primary and acquired resistance to
EGFR, HER2, and BRAF targeting agents. These findings support the notion that co
targeting of cancer cells and stromal cells is required to prevent therapeutic
resistance and to increase the overall survival rate of cancer patients. HGF
dependence has emerged as a hallmark of therapeutic resistance, suggesting that
inhibitors of biological activity of HGF should be included into therapeutic
regimens of cancer patients.
PMID- 28420163
TI - Beneficial Effects of Melatonin on the In Vitro Maturation of Sheep Oocytes and
Its Relation to Melatonin Receptors.
AB - (1) Background: The binding sites of melatonin, as a multifunctional molecule,
have been identified in human, porcine, and bovine samples. However, the binding
sites and mechanisms of melatonin have not been reported in sheep; (2) Methods:
Cumulus-oocyte complexes (COCs) were cultured in TCM-199 supplemented with
melatonin at concentrations of 0, 10-3, 10-5, 10-7, 10-9, and 10-11 M. Melatonin
receptors (MT1 and MT2) were evaluated via immunofluorescence and Western blot.
The effects of melatonin on cumulus cell expansion, nuclear maturation, embryo
development, and related gene (GDF9, DNMT1, PTX3, HAS2, and EGFR) expression were
investigated. The level of cyclic adenosine monophosphate (cAMP) and cyclic
guanosine monophosphate (cGMP) were evaluated in oocytes and cumulus,
respectively; (3) Results: Both MT1 and MT2 were expressed in oocytes, cumulus
cells, and granulosa cells. Melatonin with a concentration of 10-7 M
significantly enhanced the rates of nuclear maturation, cumulus cells expansion,
cleavage, and blastocyst. Melatonin enhanced the expression of BMP15 in oocytes
and of PTX3, HAS2, and EGFR in cumulus cells. Melatonin decreased the cAMP level
of oocytes but enhanced the cGMP level in oocytes and cumulus cells; (4)
Conclusion: The higher presence of MT1 in GV cumulus cells and the beneficial
effects of melatonin indicated that its roles in regulating sheep oocyte
maturation may be mediated mainly by the MT1 receptor.
PMID- 28420164
TI - The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat
Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral
Adipose-Tissue Function.
AB - Similar to neoplastic tissues, growth and development of adipose tissue are
thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is
associated with development and progression of nonalcoholic fatty liver disease
(NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity
induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a
high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract
ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube
formation in vitro. HFD increased VAT angiogenesis and induced weight gains
including body weight, VAT mass and visceral adipocyte size compared with LFD.
However, HFD-ALS led to weight reductions without affecting calorie intake
compared with HFD. HFD-ALS also reduced serum ALT and AST levels and improved
lipid metabolism. HFD-ALS suppressed steatosis, infiltration of inflammatory
cells, and accumulation of collagen in livers. HFD-ALS modulated hepatic
expression of genes involved in lipid metabolism, inflammation, fibrosis,
antioxidation, and apoptosis. Concomitantly, analysis of VAT function revealed
that HFD-ALS led to fewer CD68-positive macrophage numbers and lower expression
of inflammatory cytokines compared with HFD. Our findings show that the anti
angiogenic herbal extract ALS-L1023 attenuates NAFLD by targeting VAT during
obesity, suggesting that angiogenesis inhibitors could aid in the treatment and
prevention of obesity-induced human NAFLD.
PMID- 28420165
TI - Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of
Intestinal Polyps in Min Mice.
AB - Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes
the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and
its inhibitor is reported to reduce cancer cell proliferation and induce
apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could
inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice,
were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result,
acetazolamide treatment reduced the total number of intestinal polyps by up to
50% compared to the control group. In addition, the acetazolamide-treated group
had low cell proliferation and a high apoptosis ratio in the intestinal polyp
epithelial cells. Moreover, the mRNA expression level of proinflammatory
cytokines, such as IL-6, involved in the cell proliferation was decreased in the
polyp part of the acetazolamide-treated group. Next, we examined the effects of
acetazolamide on the activation of several transcriptional factors (AP-1, HIF,
HSF, NF-kappaB, NRF2, p53, and STAT3) using a reporter gene assay in human colon
cancer cells, Caco-2 cells. Among the examined transcriptional factors, NRF2
transcriptional activation was strongly induced. NRF2-targeting genes, gammaGCS,
GPx1, HO-1, and NQO-1, were also elevated in the intestinal polyps of
acetazolamide-treated Min mice. Our results suggested that CA is involved in
intestinal carcinogenesis. Acetazolamide could inhibit polyp formation through
suppressing local/general cytokine levels, i.e., IL-6, via NRF2 activation.
PMID- 28420166
TI - Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via
Regulation of TLR4 and PPAR-gamma Dependent on PI3K/Akt/mTOR Signal Pathway.
AB - Endothelial lesion response to injurious stimuli is a necessary step for
initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from
different marine sources is shown to exhibit anti-inflammatory properties.
However, the potential roles and possible molecular mechanisms of Hy in
endothelial inflammation have yet to be fully clarified. We showed that Hy
significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro
inflammatory cytokines expressions, including tumor necrosis factor-alpha (TNF
alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1)
and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the
phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome
proliferator-activated receptor gamma (PPAR-gamma) and upregulated toll-like
receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented
by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4
expressions and decreases in PPAR-gamma levels. Genetic silencing of TLR4 or PPAR
gamma agonist pioglitazone obviously abrogated the levels of pro-inflammatory
cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert
anti-inflammatory actions through the regulation of TLR4 and PPAR-gamma dependent
on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent
that can potentially relieve or ameliorate endothelial inflammation-associated
diseases.
PMID- 28420167
TI - Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to
Factor VIII/IX.
AB - The development of alloantibodies neutralising therapeutically administered
factor (F) VIII/IX (inhibitors) is currently the most severe complication of the
treatment of haemophilia. When persistent and at a high titre, inhibitors
preclude the standard replacement treatment with FVIII/FIX concentrates, making
patients' management challenging. Indeed, the efficacy of bypassing agents, i.e.,
activated prothrombin complex concentrates (aPCC) and recombinant activated
factor VII (rFVIIa), needed to overcome the haemostatic interference of the
inhibitor, is not comparable to that of factor concentrates. In addition, the
therapeutical response is unpredictable, with a relevant inter-individual and
even intra-individual variability, and no laboratory assay is validated to
monitor the efficacy and safety of the treatment. As a result, inhibitor patients
have a worse joint status and quality of life compared to inhibitor-free subjects
and the eradication of the inhibitor by immune tolerance induction is the
preeminent therapeutic goal, particularly in children. However, over the last
decades, treatment with bypassing agents has been optimised, allowing home
treatment and the individualisation of regimens aimed at improving clinical
outcomes. In this respect, a growing body of evidence supports the efficacy of
prophylaxis with both bypassing agents in reducing bleeding rates and improving
the quality of life, although the impact on long-term outcomes (in particular on
preventing/reducing joint deterioration) is still unknown. This review offers an
update on the current knowledge and practice of the use of bypassing agents in
haemophiliacs with inhibitors, as well as on debated issues and unmet needs in
this challenging setting.
PMID- 28420168
TI - Comparative Study of Blood-Based Biomarkers, alpha2,3-Sialic Acid PSA and PHI,
for High-Risk Prostate Cancer Detection.
AB - Prostate Specific Antigen (PSA) is the most commonly used serum marker for
prostate cancer (PCa), although it is not specific and sensitive enough to allow
the differential diagnosis of the more aggressive tumors. For that, new
diagnostic methods are being developed, such as PCA-3, PSA isoforms that have
resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms.
In the present study, we have compared the PHI with our recently developed PSA
glycoform assay, based on the determination of the alpha2,3-sialic acid
percentage of serum PSA (% alpha2,3-SA), in a cohort of 79 patients, which
include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH)
patients. The % alpha2,3-SA could distinguish high-risk PCa patients from the
rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs.
0.840), although the PHI correlated better with the Gleason score than the %
alpha2,3-SA. The combination of both markers increased the AUC up to 0.985
resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk
PCa from the other low and intermediate-risk PCa and BPH patients. These results
suggest that both serum markers complement each other and offer an improved
diagnostic tool to identify high-risk PCa, which is an important requirement for
guiding treatment decisions.
PMID- 28420169
TI - Ultrasensitive Label-Free Sensing of IL-6 Based on PASE Functionalized Carbon
Nanotube Micro-Arrays with RNA-Aptamers as Molecular Recognition Elements.
AB - This study demonstrates the rapid and label-free detection of Interleukin-6 (IL
6) using carbon nanotube micro-arrays with aptamer as the molecular recognition
element. Single wall carbon nanotubes micro-arrays biosensors were manufactured
using photo-lithography, metal deposition, and etching techniques. Nanotube
biosensors were functionalized with 1-Pyrenebutanoic Acid Succinimidyl Ester
(PASE) conjugated IL-6 aptamers. Real time response of the sensor conductance was
monitored with increasing concentration of IL-6 (1 pg/mL to 10 ng/mL), exposure
to the sensing surface in buffer solution, and clinically relevant spiked blood
samples. Non-specific Bovine Serum Albumin (BSA), PBS samples, and anti-IgG
functionalized devices gave similar signatures in the real time conductance
versus time experiments with no significant change in sensor signal. Exposure of
the aptamer functionalized nanotube surface to IL-6 decreased the conductance
with increasing concentration of IL-6. Experiments based on field effect
transistor arrays suggested shift in drain current versus gate voltage for 1 pg
and 1 ng of IL-6 exposure. Non-specific BSA did not produce any appreciable shift
in the Ids versus Vg suggesting specific interactions of IL-6 on PASE conjugated
aptamer surface gave rise to the change in electrical signal. Both Z axis and
phase image in an Atomic Force Microscope (AFM) suggested unambiguous molecular
interaction of the IL-6 on the nanotube-aptamer surface at 1 pg/mL concentration.
The concentration of 1 pg falls below the diagnostic gray zone for cancer (2.3 pg
4 ng/mL), which is an indicator of early stage cancer. Thus, nanotube micro
arrays could potentially be developed for creating multiplexed assays involving
cancer biomarker proteins and possibly circulating tumor cells all in a single
assay using PASE functionalization protocol.
PMID- 28420170
TI - Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive
Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1
and MAPK Signaling in PC12 Cells.
AB - BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and
exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However,
high concentration of fisetin is reported to produce reactive oxygen species
(ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer
cells. The aim of this study is to investigate the cytoprotective effects of low
concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in
neuronal-like catecholaminergic PC12 cells. METHODS: Cell viability was assayed
by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and
apoptotic and autophagic markers were analyzed by Western blot. Gene expression
of unfolded protein response (UPR) and Phase II enzymes was further investigated
using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using
2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The
effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1
(Sirtuin 1) signaling pathways were examined using Western blotting and specific
inhibitors. RESULTS: Fisetin (<20 uM) restored cell viability and repressed
apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated
Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78
(GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles
homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2
targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and
cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of
Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal
regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK.
Addition of JNK and p38 MAPK inhibitor significantly antagonized its
cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm
inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor)
significantly blocked fisetin-mediated cytoprotection. In conclusion, this result
shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive
cellular stress response pathways so as to protect cells from Tm-induced
cytotoxicity.
PMID- 28420171
TI - Pannexin- and Connexin-Mediated Intercellular Communication in Platelet Function.
AB - The three major blood cell types, i.e., platelets, erythrocytes and leukocytes,
are all produced in the bone marrow. While red blood cells are the most numerous
and white cells are the largest, platelets are small fragments and account for a
minor part of blood volume. However, platelets display a crucial function by
preventing bleeding. Upon vessel wall injury, platelets adhere to exposed
extracellular matrix, become activated, and form a platelet plug preventing
hemorrhagic events. However, when platelet activation is exacerbated, as in
rupture of an atherosclerotic plaque, the same mechanism may lead to acute
thrombosis causing major ischemic events such as myocardial infarction or stroke.
In the past few years, major progress has been made in understanding of platelet
function modulation. In this respect, membrane channels formed by connexins
and/or pannexins are of particular interest. While it is still not completely
understood whether connexins function as hemichannels or gap junction channels to
inhibit platelet aggregation, there is clear-cut evidence for a specific
implication of pannexin1 channels in collagen-induced aggregation. The focus of
this review is to summarize current knowledge of the role of connexins and
pannexins in platelet aggregation and to discuss possible pharmacological
approaches along with their limitations and future perspectives for new potential
therapies.
PMID- 28420173
TI - Transcriptome Sequencing of Dianthus spiculifolius and Analysis of the Genes
Involved in Responses to Combined Cold and Drought Stress.
AB - Dianthus spiculifolius, a perennial herbaceous flower and a member of the
Caryophyllaceae family, has strong resistance to cold and drought stresses. To
explore the transcriptional responses of D. spiculifolius to individual and
combined stresses, we performed transcriptome sequencing of seedlings under
normal conditions or subjected to cold treatment (CT), simulated drought
treatment (DT), or their combination (CTDT). After de novo assembly of the
obtained reads, 112,015 unigenes were generated. Analysis of differentially
expressed genes (DEGs) showed that 2026, 940, and 2346 genes were up-regulated
and 1468, 707, and 1759 were down-regulated in CT, DT, and CTDT samples,
respectively. Among all the DEGs, 182 up-regulated and 116 down-regulated genes
were identified in all the treatment groups. Analysis of metabolic pathways and
regulatory networks associated with the DEGs revealed overlaps and cross-talk
between cold and drought stress response pathways. The expression profiles of the
selected DEGs in CT, DT, and CTDT samples were characterized and confirmed by
quantitative RT-PCR. These DEGs and metabolic pathways may play important roles
in the response of D. spiculifolius to the combined stress. Functional
characterization of these genes and pathways will provide new targets for
enhancement of plant stress tolerance through genetic manipulation.
PMID- 28420174
TI - An Expedient Total Synthesis of Triciribine.
AB - In the present paper, we report an expedient total synthesis of triciribine, a
tricyclic 7-deazapurine nucleoside and protein kinase B (AKT ) inhibitor, in 35%
overall yield. Our synthesis route features a highly regioselective substitution
of 1-N-Boc-2-methylhydrazine and a trifluoroacetic acid catalyzed one-pot
transformation which combined the deprotection of the tert-butylcarbonyl (Boc)
group and ring closure reaction together to give a tricyclic nucleobase motif.
PMID- 28420172
TI - Subtype Diagnosis of Primary Aldosteronism: Is Adrenal Vein Sampling Always
Necessary?
AB - Aldosterone producing adenoma and bilateral adrenal hyperplasia are the two most
common subtypes of primary aldosteronism (PA) that require targeted and distinct
therapeutic approaches: unilateral adrenalectomy or lifelong medical therapy with
mineralocorticoid receptor antagonists. According to the 2016 Endocrine Society
Guideline, adrenal venous sampling (AVS) is the gold standard test to distinguish
between unilateral and bilateral aldosterone overproduction and therefore, to
safely refer patients with PA to surgery. Despite significant advances in the
optimization of the AVS procedure and the interpretation of hormonal data, a
standardized protocol across centers is still lacking. Alternative methods are
sought to either localize an aldosterone producing adenoma or to predict the
presence of unilateral disease and thereby substantially reduce the number of
patients with PA who proceed to AVS. In this review, we summarize the recent
advances in subtyping PA for the diagnosis of unilateral and bilateral disease.
We focus on the developments in the AVS procedure, the interpretation criteria,
and comparisons of the performance of AVS with the alternative methods that are
currently available.
PMID- 28420175
TI - A New Input Device for Spastics Based on Strain Gauge.
AB - This article presents a new sensor for use by people with spastic disorders and
similar conditions and enables them to steer and control medical devices such as
electric powered wheelchairs. As spastic patients often suffer from cramping of
their extremities, which can then no longer be controlled, using a standard
joystick while operating a powered wheelchair can lead to dangerous situations.
To prevent this, we designed a sensor based on strain gauges, which is shaped
like a flat disc that can be operated using any body part. By shifting weight
along the x- and y-axis, the disc tilts in all directions thereby generating
proportionate output signals. The disc can also be pressed downward (z-axis), for
example, to open a wheelchair's menu. Thanks to the sensor's flat disc-like
construction and the option of mounting it into a control panel, users are not in
danger of becoming stuck on the disc during spastic episodes. In the event of a
spasm, body parts simply slide over the disc reducing risk of unintended actions.
The sensor is adaptive and adjustable enabling it to fit a user's range of
strength and motion at any time. It was developed to ensure users can operate
sensitive systems safely.
PMID- 28420176
TI - Establishing Reliable Cu-64 Production Process: From Target Plating to Molecular
Specific Tumor Micro-PET Imaging.
AB - Copper-64 is a useful radioisotope for positron emission tomography (PET). Due to
the wide range of applications, the demand of 64Cu with low metallic impurities
is increasing. Here we report a simple method for the efficient production of
high specific activity 64Cu using a cyclotron for biomedical application. We
designed new equipment based on the plating of enriched 64Ni as the target, and
used automated ion exchange chromatography to purify copper-64 efficiently after
irradiation and dissolution of the target in good radiochemical and chemical
yield and purity. The 64Cu radionuclide produced using 99.32% enriched 64Ni with
a density of 61.4 +/- 5.0 mg/cm2, reaching a total radioactivity greater than 200
mCi, with specific activity up to 5.6 GBq/MUmoL. It was further incorporated into
modified monoclonal antibody DOTA-rituximab to synthesize 64Cu-DOTA-rituximab,
which was used successfully for micro-PET imaging.
PMID- 28420178
TI - How Older Adults and Their Families Perceive Family Talk about Aging-Related EOL
Issues: A Dialectical Analysis.
AB - For older adults, approaching end-of-life (EOL) brings unique transitions related
to family relationships. Unfortunately, most families greatly underestimate the
need to discuss these difficult issues. For example, parents approaching EOL
issues often struggle with receiving assistance from others, avoiding family
conflict, and maintaining their sense of personhood. In addition, discussions of
EOL issues force family members to face their parents' mortality, which can be
particularly difficult for adult children to process emotionally. This study
explored aging issues identified by aging parents and their families as they
traverse these impending EOL changes. Ten focus groups of seniors (n = 65) were
conducted. Focus groups were organized according to race (African
American/European-American), gender, and whether the older adult was living
independently or in an assisted care facility. When asked open-ended questions
about discussing aging and EOL issues with family members, participants revealed
tensions that led us to consider Relational Dialectics Theory as a framework for
analysis. The predominant tension highlighted in this report was certainty versus
uncertainty, with the two sub-themes of sustained life versus sustained
personhood and confronting versus avoiding EOL issues. For these data, there were
more similarities than differences as a result of gender, race, or living
situation than one might expect, although culture and financial status were found
to be influential in the avoidance of EOL discussions. The results of this study
help to provide additional insight into relational dialectics related to aging,
EOL, and the importance of communication in facilitating family coping.
PMID- 28420177
TI - Molecular Hybridization-Guided One-Pot Multicomponent Synthesis of Turmerone
Motif-Fused 3,3'-Pyrrolidinyl-dispirooxindoles via a 1,3-Dipolar Cycloaddition
Reaction.
AB - Described herein is the development of a facile and efficient methodology for the
synthesis of novel turmerone motif-fused 3,3'-pyrrolidinyl-dispirooxindoles 3-5
via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine
ylides (thermally generated in situfrom isatins and proline or thioproline or
sarcosine). Products bearing four or three consecutive stereocenters consist of
two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary
stereocenters fused in one ring structure were smoothly obtained in high yields
(up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable
application of this method was for the design of new hybrid architectures for
biological screening through the adequate fusion of these sub-units of turmerone
and 3,3'-pyrrolidinyl-dispirooxindole, generating drug-like molecules.
PMID- 28420179
TI - Systematic Understanding of the Mechanism of Salvianolic Acid A via Computational
Target Fishing.
AB - Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent
anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A
systematic overview of its mechanism of action is yet to be performed. In the
present study, the druggability of SAA was measured using the TCMSP server, and
potential targets of SAA were identified by PharmMapper and DRAR-CPI.
Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and
drug-target-pathway networks were constructed to give a visual view. The results
showed that SAA has good druggability, and 13 putative protein targets were
identified. Network analysis showed that these targets were associated with
cancer, metabolism and other physiological processes. In summary, SAA is
predicted to target multiple proteins and pathways to form a network that exerts
systematic pharmacological effects.
PMID- 28420180
TI - Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid
Podophyllotoxin Conjugate towards Human Gastric Cancer Cells.
AB - With the purpose of creating a multifunctional drug for gastric cancer treatment,
a novel all-trans-retinoic acid (ATRA) conjugate with podophyllotoxin (PPT) was
designed and synthesized, and its in vitro antiproliferative activity was
evaluated against human gastric cancer cell lines using CCK-8 assay. The
conjugate, P-A, exhibited significant anticancer activity against MKN-45 and BGC
823 cells with IC50 values of 0.419 +/- 0.032 and 0.202 +/- 0.055 MUM,
respectively. Moreover, P-A efficiently triggered cell cycle arrest and induced
apoptosis in MKN-45 and BGC-823 cells due to modulation of cell cycle arrest-
(CDK1, CDK2, CyclinA and CyclinB1) and apoptosis- (cleaved caspase-3, -8 and -9)
related proteins, respectively. Further mechanism studies revealed that P-A could
increase the expression levels of RARalpha and RARbeta, and decrease the level of
RARgamma in MKN-45 and BGC-823 cells. Finally, P-A inhibited the ERK1/2 and AKT
signaling in the above two cancer cell lines. More importantly, the underlying
mechanisms of P-A were similar to those of precursor PPT but different with the
other precursor ATRA. Together, the conjugate P-A was a promising candidate for
the potential treatment of human gastric cancer.
PMID- 28420182
TI - Nanoscale in Photocatalysis.
AB - n/a.
PMID- 28420181
TI - Comment on Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies. Toxins
2016, 8, 358.
AB - Recently, the clinical and experimental evidences that support the toxic effects
of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD)
patients, has been discussed. In this panorama, the authors described several in
vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the
pathogenesis of low turnover bone disease. However, the discussion claims the
need for relevant clinical studies in CKD patients whose bone turnover biomarkers
and bone histomorphometry were assessed in order to demonstrate the association
between serum levels of indoxyl sulfate and bone turnover. We would like to
underline the availability of this clinical data to support the concept that
indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease
in CKD patients.
PMID- 28420183
TI - Anti-Proliferative Effect of Triterpenoidal Glycosides from the Roots of Anemone
vitifolia through a Pro-Apoptotic Way.
AB - A cytotoxicity-guided phytochemical investigation of Anemone vitifolia roots led
to the isolation of six oleanane saponins (1-6), which were reported from the
species for the first time. Their structures were determined by comparing its MS
and NMR data with those in literature. Compounds 1-4 showed significant
inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells
with IC50 values ranging from 2.0 to 8.5 MUM, compared to positive control
methotrexate with IC50 value of 15.8 MUM. Flow cytometry analysis revealed that
compounds 1-4 exerted anti-proliferative effects through a pro-apoptotic way of
hepatocellular carcinoma cells.
PMID- 28420184
TI - Metajapogenins A-C, Pregnane Steroids from Shells of Metaplexis japonica.
AB - Phytochemical investigation of the shells of Metaplexis japonica (Thunb.) Makino,
belonging to the family of Apocynaceae, afforded three new pregnane steroids,
metajapogenins A-C, along with three known compounds. The structures of the new
compounds were elucidated as 12beta,14beta,17beta-trihydroxypregna-3,5-dien-7,20
dione, 12beta,14beta,17beta,20beta-tetrahydroxypregna-3,5-dien-7-one;
3beta,12beta,14beta,17beta-tetrahydroxypregn-5-ene-7,20-dione on the basis of
extensive spectroscopic evidence derived from 1D; 2D-NMR experiments and mass
spectrometry. The known compounds included pergularin; 12-O-acetylpergularin; and
pergularin-3-O-beta-d-oleandropyranose; which were identified for the first time
in the shells of M. japonica.
PMID- 28420186
TI - Using Moss to Assess Airborne Heavy Metal Pollution in Taizhou, China.
AB - Bryophytes act as bioindicators and bioaccumulators of metal deposition in the
environment. To understand the atmospheric deposition of heavy metals (cadmium
(Cd), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc
(Zn)) in Taizhou, East China, samples of moss (Haplocladium microphyllum) were
collected from 60 sites selected by a systematic sampling method during the
summer of 2012, and the concentrations of these heavy metals were determined by
inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results
suggested that the concentrations of these metals varied moderately among
different sites, indicating a similar contamination level for each element
throughout the monitoring region. The mean values under investigation were higher
than those from neighboring cities, such as Wuxi, Xuzhou, and Nanjing, and much
higher than those in Europe based on a 2010 survey. Significant (p < 0.01)
correlations were identified among some of the heavy metals, suggesting that
these originated from identical sources. There was no statistically significant
correlation between Hg and all the other elements. Spatial distribution maps of
the elements over the sampled territory were created using Arc-GIS 9.0. The
potential ecological risk index indicated that the air was heavily polluted by Cd
and Hg, and that there was a considerable potential ecological risk from all the
heavy metals studied.
PMID- 28420187
TI - Device-Free Localization via an Extreme Learning Machine with Parameterized
Geometrical Feature Extraction.
AB - Device-free localization (DFL) is becoming one of the new technologies in
wireless localization field, due to its advantage that the target to be localized
does not need to be attached to any electronic device. In the radio-frequency
(RF) DFL system, radio transmitters (RTs) and radio receivers (RXs) are used to
sense the target collaboratively, and the location of the target can be estimated
by fusing the changes of the received signal strength (RSS) measurements
associated with the wireless links. In this paper, we will propose an extreme
learning machine (ELM) approach for DFL, to improve the efficiency and the
accuracy of the localization algorithm. Different from the conventional machine
learning approaches for wireless localization, in which the above differential
RSS measurements are trivially used as the only input features, we introduce the
parameterized geometrical representation for an affected link, which consists of
its geometrical intercepts and differential RSS measurement. Parameterized
geometrical feature extraction (PGFE) is performed for the affected links and the
features are used as the inputs of ELM. The proposed PGFE-ELM for DFL is trained
in the offline phase and performed for real-time localization in the online
phase, where the estimated location of the target is obtained through the created
ELM. PGFE-ELM has the advantages that the affected links used by ELM in the
online phase can be different from those used for training in the offline phase,
and can be more robust to deal with the uncertain combination of the detectable
wireless links. Experimental results show that the proposed PGFE-ELM can improve
the localization accuracy and learning speed significantly compared with a number
of the existing machine learning and DFL approaches, including the weighted K
nearest neighbor (WKNN), support vector machine (SVM), back propagation neural
network (BPNN), as well as the well-known radio tomographic imaging (RTI) DFL
approach.
PMID- 28420188
TI - Health Risk Assessment of Indoor Air Quality, Socioeconomic and House
Characteristics on Respiratory Health among Women and Children of Tirupur, South
India.
AB - Background: Indoor air pollution is still considered as one of the leading causes
of morbidity and mortality worldwide and especially in developing countries,
including India. This study aims to assess social, housing, and indoor
environmental factors associated with respiratory health among mothers and
children. Methods: The study was conducted in the city of Tirupur, South India.
We quantitatively assessed the indoor exposure to fine particulate matter (PM2.5)
and carbon monoxide in relation to respiratory health among women and children.
Information on health status, household characteristics and socioeconomic factors
was collected using a modified standardised questionnaire. Results: This study
demonstrates the significant health impact of housing and socioeconomic
characteristics on the burden of respiratory illness among women and children in
urban South India. Increased respiratory symptoms were recorded among women and
children from low income households, and those who allowed smoking inside. The
mean PM2.5 concentration measured in this study was 3.8 mg/m3 which exceeded the
World Health Organization (WHO) 24 h guideline value of 0.025 mg/m3. Conclusions:
This study is the first to our knowledge carried out in urban South India and the
findings can be used for future intervention studies.
PMID- 28420189
TI - Demographic and Environmental Factors Associated with Mental Health: A Cross
Sectional Study.
AB - Relevant demographic and environmental conditions need to be understood before
tailoring policies to improve mental health. Using community health survey data
from 25 communities in Seoul, 2013, cross-sectional associations between mental
health and community level environments were assessed. Mental health outcomes
(self-rated stress levels (SRS) and depressive symptoms (DS)) were analyzed.
Community environmental factors included green space, green facilities, and
annual PM10 level (AnnPM10); socio-demographic factors included sex, age,
education, labor market participation, comorbidity, sleep hours, physical
activity, smoking, and drinking. A total of 23,139 people with the following
characteristics participated: men (44.2%); age groups 19-39 (36.0%), 40-59
(39.4%), 60-74 (19.2%), and 75+ (5.4%). Women had higher odds ratios (OR) for SRS
[OR 1.22, 95% Confidence interval (CI) 1.17-1.27] and DS [OR 1.55, 95% CI 1.42
1.71]. Regular physical activity predicted SRS [OR 0.90, 95% CI 0.84-0.95] and DS
[OR 0.98, 95% CI 0.88-1.10]; current smoking and drinking were adversely
associated with both SRS and DS. Higher accessibility to green space (Q4) was
inversely associated with DS [OR 0.89, 95% CI 0.81-0.97] compared to lower
accessibility (Q1). AnnPM10, annual levels for particles of aerodynamic diameter
<10 um (PM10), among communities was associated with poorer SRS [OR 1.02, 95% CI
1.00-1.04] by 10 MUg/m3 increases. Therefore, both demographic and environmental
factors should be considered to understand mental health conditions among the
general population.
PMID- 28420190
TI - Overexpression of S-Adenosyl-l-Methionine Synthetase 2 from Sugar Beet M14
Increased Arabidopsis Tolerance to Salt and Oxidative Stress.
AB - The sugar beet monosomic addition line M14 is a unique germplasm that contains
genetic materials from Beta vulgaris L. and Beta corolliflora Zoss, and shows
tolerance to salt stress. Our study focuses on exploring the molecular mechanism
of the salt tolerance of the sugar beet M14. In order to identify differentially
expressed genes in M14 under salt stress, a subtractive cDNA library was
generated by suppression subtractive hybridization (SSH). A total of 36 unique
sequences were identified in the library and their putative functions were
analyzed. One of the genes, S-adenosylmethionine synthetase (SAMS), is the key
enzyme involved in the biosynthesis of S-adenosylmethionine (SAM), a precursor of
polyamines. To determine the potential role of SAMS in salt tolerance, we
isolated BvM14-SAMS2 from the salt-tolerant sugar beet M14. The expression of
BvM14-SAMS2 in leaves and roots was greatly induced by salt stress.
Overexpression of BvM14-SAMS2 in Arabidopsis resulted in enhanced salt and H2O2
tolerance. Furthermore, we obtained a knock-down T-DNA insertion mutant of
AtSAMS3, which shares the highest homology with BvM14-SAMS2. Interestingly, the
mutant atsam3 showed sensitivity to salt and H2O2 stress. We also found that the
antioxidant system and polyamine metabolism play an important role in salt and
H2O2 tolerance in the BvM14-SAMS2-overexpressed plants. To our knowledge, the
function of the sugar beet SAMS has not been reported before. Our results have
provided new insights into SAMS functions in sugar beet.
PMID- 28420191
TI - Designing Effective Interactions for Concordance around End-of-Life Care
Decisions: Lessons from Hospice Admission Nurses.
AB - Near the end of life, hospice care reduces symptom-related distress and
hospitalizations while improving caregiving outcomes. However, it takes time for
a person to gain a sufficient understanding of hospice and decide to enroll. This
decision is influenced by knowledge of hospice and its services, emotion and
fear, cultural and religious beliefs, and an individual's acceptance of
diagnosis. Hospice admission interactions, a key influence in shaping decisions
regarding hospice care, happen particularly late in the illness trajectory and
are often complex, unpredictable, and highly variable. One goal of these
interactions is ensuring patients and families have accurate and clear
information about hospice care to facilitate informed decisions. So inconsistent
are practices across hospices in consenting patients that a 2016 report from the
Office of Inspector General (OIG) entitled "Hospices should improve their
election statements and certifications of terminal illness" called for complete
and accurate election statements to ensure that hospice patients and their
caregivers can make informed decisions and understand the costs and benefits of
choosing hospice care. Whether complete and accurate information at initial
admission visits improves interactions and outcomes is unknown. Our recent
qualitative work investigating interactions between patients, caregivers, and
hospice nurses has uncovered diverse and often diverging stakeholder-specific
expectations and perceptions which if not addressed can create discordance and
inhibit decision-making. This paper focuses on better understanding the
communication dynamics and practices involved in hospice admission interactions
in order to design more effective interactions and support the mandate from the
OIG to provide hospice patients and their caregivers with accurate and complete
information. This clarity is particularly important when discussing the non
curative nature of hospice care, and the choice patients make to forego
aggressive treatment measures when they enroll in hospice. In a literal sense, to
enroll in hospice means to bring in support for end-of-life care. It means to
identify the need for expertise around symptom management at end-of-life, and
agree to having a care team come and manage someone's physical, psychosocial,
and/or spiritual needs. As with all care, hospice can be stopped if it is no
longer considered appropriate. To uncover the communication tensions undergirding
a hospice admission interaction, we use Street's ecological theory of patient
centered communication to analyze a case exemplar of a hospice admission
interaction. This analysis reveals diverse points of struggle within hospice
decision-making processes around hospice care and the need for communication
techniques that promote trust and acceptance of end-of-life care. Lessons learned
from talking about hospice care can inform other quality initiatives around
communication and informed decision-making in the context of advance care
planning, palliative care, and end-of-life care.
PMID- 28420185
TI - Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation,
Progression and Metastasis.
AB - There is highly credible evidence that melatonin mitigates cancer at the
initiation, progression and metastasis phases. In many cases, the molecular
mechanisms underpinning these inhibitory actions have been proposed. What is
rather perplexing, however, is the large number of processes by which melatonin
reportedly restrains cancer development and growth. These diverse actions suggest
that what is being observed are merely epiphenomena of an underlying more
fundamental action of melatonin that remains to be disclosed. Some of the
arresting actions of melatonin on cancer are clearly membrane receptor-mediated
while others are membrane receptor-independent and involve direct intracellular
actions of this ubiquitously-distributed molecule. While the emphasis of
melatonin/cancer research has been on the role of the indoleamine in restraining
breast cancer, this is changing quickly with many cancer types having been shown
to be susceptible to inhibition by melatonin. There are several facets of this
research which could have immediate applications at the clinical level. Many
studies have shown that melatonin's co-administration improves the sensitivity of
cancers to inhibition by conventional drugs. Even more important are the findings
that melatonin renders cancers previously totally resistant to treatment
sensitive to these same therapies. Melatonin also inhibits molecular processes
associated with metastasis by limiting the entrance of cancer cells into the
vascular system and preventing them from establishing secondary growths at
distant sites. This is of particular importance since cancer metastasis often
significantly contributes to death of the patient. Another area that deserves
additional consideration is related to the capacity of melatonin in reducing the
toxic consequences of anti-cancer drugs while increasing their efficacy. Although
this information has been available for more than a decade, it has not been
adequately exploited at the clinical level. Even if the only beneficial actions
of melatonin in cancer patients are its ability to attenuate acute and long-term
drug toxicity, melatonin should be used to improve the physical wellbeing of the
patients. The experimental findings, however, suggest that the advantages of
using melatonin as a co-treatment with conventional cancer therapies would far
exceed improvements in the wellbeing of the patients.
PMID- 28420192
TI - Thioredoxin-Interacting Protein Mediates Apoptosis in Early Brain Injury after
Subarachnoid Haemorrhage.
AB - Early brain injury (EBI) is considered to be the major factor associated with
high morbidity and mortality after subarachnoid haemorrhage (SAH). Apoptosis is
the major pathological mechanism of EBI, and its pathogenesis has not been fully
clarified. Here, we report that thioredoxin-interacting protein (TXNIP), which is
induced by protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK),
participates in EBI by promoting apoptosis. By using adult male Sprague-Dawley
rats to establish SAH models, as well as Terminal dexynucleotidyl transferase
(TdT)-mediated dUTP nick end labeling (TUNEL) staining, immunofluorescence, and
western blot, we found that TXNIP expression significantly increased after SAH in
comparison to the sham group and peaked at 48 h (up to 3.2-fold). Meanwhile,
TXNIP was widely expressed in neurons and colocalized with TUNEL-positive cells
in the hippocampus and cortex of SAH rats. After administration of TXNIP
inhibitor-resveratrol (60 mg/kg), TXNIP small interfering RNA (siRNA) and the
PERK inhibitor GSK2656157, TXNIP expression was significantly reduced,
accompanied by an attenuation of apoptosis and prognostic indicators, including
SAH grade, neurological deficits, brain water content, and blood-brain barrier
(BBB) permeability. Collectively, these results suggest that TXNIP may
participate in EBI after SAH by mediating apoptosis. The blockage of TXNIP
induced by PERK could be a potential therapeutic strategy for SAH treatment.
PMID- 28420193
TI - A Quantitative PCR-Electrochemical Genosensor Test for the Screening of Biotech
Crops.
AB - The design of screening methods for the detection of genetically modified
organisms (GMOs) in food would improve the efficiency in their control. We report
here a PCR amplification method combined with a sequence-specific electrochemical
genosensor for the quantification of a DNA sequence characteristic of the 35S
promoter derived from the cauliflower mosaic virus (CaMV). Specifically, we
employ a genosensor constructed by chemisorption of a thiolated capture probe and
p-aminothiophenol gold surfaces to entrap on the sensing layer the unpurified PCR
amplicons, together with a signaling probe labeled with fluorescein. The proposed
test allows for the determination of a transgene copy number in both hemizygous
(maize MON810 trait) and homozygous (soybean GTS40-3-2) transformed plants, and
exhibits a limit of quantification of at least 0.25% for both kinds of GMO lines.
PMID- 28420194
TI - Multiple Objects Fusion Tracker Using a Matching Network for Adaptively
Represented Instance Pairs.
AB - Multiple-object tracking is affected by various sources of distortion, such as
occlusion, illumination variations and motion changes. Overcoming these
distortions by tracking on RGB frames, such as shifting, has limitations because
of material distortions caused by RGB frames. To overcome these distortions, we
propose a multiple-object fusion tracker (MOFT), which uses a combination of 3D
point clouds and corresponding RGB frames. The MOFT uses a matching function
initialized on large-scale external sequences to determine which candidates in
the current frame match with the target object in the previous frame. After
conducting tracking on a few frames, the initialized matching function is fine
tuned according to the appearance models of target objects. The fine-tuning
process of the matching function is constructed as a structured form with diverse
matching function branches. In general multiple object tracking situations, scale
variations for a scene occur depending on the distance between the target objects
and the sensors. If the target objects in various scales are equally represented
with the same strategy, information losses will occur for any representation of
the target objects. In this paper, the output map of the convolutional layer
obtained from a pre-trained convolutional neural network is used to adaptively
represent instances without information loss. In addition, MOFT fuses the
tracking results obtained from each modality at the decision level to compensate
the tracking failures of each modality using basic belief assignment, rather than
fusing modalities by selectively using the features of each modality.
Experimental results indicate that the proposed tracker provides state-of-the-art
performance considering multiple objects tracking (MOT) and KITTIbenchmarks.
PMID- 28420195
TI - Carbon Nanotube-Based Chemiresistive Sensors.
AB - The development of simple and low-cost chemical sensors is critically important
for improving human life. Many types of chemical sensors have been developed.
Among them, the chemiresistive sensors receive particular attention because of
their simple structure, the ease of high precise measurement and the low cost.
This review mainly focuses on carbon nanotube (CNT)-based chemiresistive sensors.
We first describe the properties of CNTs and the structure of CNT chemiresistive
sensors. Next, the sensing mechanism and the performance parameters of the
sensors are discussed. Then, we detail the status of the CNT chemiresistive
sensors for detection of different analytes. Lastly, we put forward the remaining
challenges for CNT chemiresistive sensors and outlook the possible opportunity
for CNT chemiresistive sensors in the future.
PMID- 28420196
TI - Probe Sensor Using Nanostructured Multi-Walled Carbon Nanotube Yarn for Selective
and Sensitive Detection of Dopamine.
AB - The demands for electrochemical sensor materials with high strength and
durability in physiological conditions continue to grow and novel approaches are
being enabled by the advent of new electromaterials and novel fabrication
technologies. Herein, we demonstrate a probe-style electrochemical sensor using
highly flexible and conductive multi-walled carbon nanotubes (MWNT) yarns. The
MWNT yarn-based sensors can be fabricated onto micro Pt-wire with a controlled
diameter varying from 100 to 300 um, and then further modified with Nafion via a
dip-coating approach. The fabricated micro-sized sensors were characterized by
electron microscopy, Raman, FTIR, electrical, and electrochemical measurements.
For the first time, the MWNT/Nafion yarn-based probe sensors have been assembled
and assessed for high-performance dopamine sensing, showing a significant
improvement in both sensitivity and selectivity in dopamine detection in presence
of ascorbic acid and uric acid. It offers the potential to be further developed
as implantable probe sensors.
PMID- 28420197
TI - A Novel Auto-Sorting System for Chinese Cabbage Seeds.
AB - This paper presents a novel machine vision-based auto-sorting system for Chinese
cabbage seeds. The system comprises an inlet-outlet mechanism, machine vision
hardware and software, and control system for sorting seed quality. The proposed
method can estimate the shape, color, and textural features of seeds that are
provided as input neurons of neural networks in order to classify seeds as "good"
and "not good" (NG). The results show the accuracies of classification to be
91.53% and 88.95% for good and NG seeds, respectively. The experimental results
indicate that Chinese cabbage seeds can be sorted efficiently using the developed
system.
PMID- 28420198
TI - Chemical Constituents of Supercritical Extracts from Alpinia officinarum and the
Feeding Deterrent Activity against Tribolium castaneum.
AB - Alpinia officinarum has been confirmed to possess bioactivities against some
pests. In this work, a sample was obtained from A. officinarum rhizomes by
supercritical fluid CO2 extraction (SFE). According to GC-MS analysis, the main
chemical components for SFE-sample included benzylacetone (26.77%), 1,7-diphenyl
5-hydroxy-3-heptanone (17.78%), guaiacylacetone (10.03%) and benzenepropanal
(7.42%). The essential oil of A. officinarum rhizomes (LD50 = 20.71 MUg/adult)
exhibited more contact toxicity than SFE extract (LD50 = 82.72 MUg/adult) against
Tribolium castaneum. From SFE extracts, one new compound, 1-phenyl-4-(16,17
dimethyl-9,13-octadiene)-5-isopentenyl-7-(4"-methoxyl-3"-hydroxyl-phenyl)-3
heptanone (3), together with five known compounds identified as 5-hydroxy-1,7
diphenyl-3-heptanone (1), 1,7-diphenyl-4-hepten-3-one (2), galangin (4), galangin
3-methyl ether (5) and pinocembrin (6), were isolated and their feeding deterrent
activities against T. castaneum adults were assessed. It was found that compounds
1-6 had feeding deterrent activities against T. castaneum with feeding deterrent
indices of 18.21%, 18.94%, 19.79%, 26.99%, 20.34%, and 35.81%, respectively, at
the concentration of 1500 ppm. Hence, the essential oil and SFE
extracts/compounds of A. officinarum rhizomes represent promising alternatives in
the control of T. castaneum adults.
PMID- 28420199
TI - Detecting Single-Nucleotides by Tunneling Current Measurements at Sub-MHz
Temporal Resolution.
AB - Label-free detection of single-nucleotides was performed by fast tunneling
current measurements in a polar solvent at 1 MHz sampling rate using SiO2
protected Au nanoprobes. Short current spikes were observed, suggestive of
trapping/detrapping of individual nucleotides between the nanoelectrodes. The
fall and rise features of the electrical signatures indicated signal retardation
by capacitance effects with a time constant of about 10 microseconds. The high
temporal resolution revealed current fluctuations, reflecting the molecular
conformation degrees of freedom in the electrode gap. The method presented in
this work may enable direct characterizations of dynamic changes in single
molecule conformations in an electrode gap in liquid.
PMID- 28420201
TI - A Transcriptomic Comparison of Two Bambara Groundnut Landraces under Dehydration
Stress.
AB - The ability to grow crops under low-water conditions is a significant advantage
in relation to global food security. Bambara groundnut is an underutilised crop
grown by subsistence farmers in Africa and is known to survive in regions of
water deficit. This study focuses on the analysis of the transcriptomic changes
in two bambara groundnut landraces in response to dehydration stress. A cross
species hybridisation approach based on the Soybean Affymetrix GeneChip array has
been employed. The differential gene expression analysis of a water-limited
treatment, however, showed that the two landraces responded with almost
completely different sets of genes. Hence, both landraces with very similar
genotypes (as assessed by the hybridisation of genomic DNA onto the Soybean
Affymetrix GeneChip) showed contrasting transcriptional behaviour in response to
dehydration stress. In addition, both genotypes showed a high expression of
dehydration-associated genes, even under water-sufficient conditions. Several
gene regulators were identified as potentially important. Some are already known,
such as WRKY40, but others may also be considered, namely PRR7, ATAUX2-11,
CONSTANS-like 1, MYB60, AGL-83, and a Zinc-finger protein. These data provide a
basis for drought trait research in the bambara groundnut, which will facilitate
functional genomics studies. An analysis of this dataset has identified that both
genotypes appear to be in a dehydration-ready state, even in the absence of
dehydration stress, and may have adapted in different ways to achieve drought
resistance. This will help in understanding the mechanisms underlying the ability
of crops to produce viable yields under drought conditions. In addition, cross
species hybridisation to the soybean microarray has been shown to be informative
for investigating the bambara groundnut transcriptome.
PMID- 28420200
TI - Integrating Spatial Working Memory and Remote Memory: Interactions between the
Medial Prefrontal Cortex and Hippocampus.
AB - In recent years, two separate research streams have focused on information
sharing between the medial prefrontal cortex (mPFC) and hippocampus (HC).
Research into spatial working memory has shown that successful execution of many
types of behaviors requires synchronous activity in the theta range between the
mPFC and HC, whereas studies of memory consolidation have shown that shifts in
area dependency may be temporally modulated. While the nature of information that
is being communicated is still unclear, spatial working memory and remote memory
recall is reliant on interactions between these two areas. This review will
present recent evidence that shows that these two processes are not as separate
as they first appeared. We will also present a novel conceptualization of the
nature of the medial prefrontal representation and how this might help explain
this area's role in spatial working memory and remote memory recall.
PMID- 28420202
TI - Cereal Consumption among Subjects with Celiac Disease: A Snapshot for Nutritional
Considerations.
AB - BACKGROUND: To our knowledge no study has focused on the pattern of cereal-based
products (CBP) consumption among people with celiac disease (CD). Our study aimed
at evaluating the dietary intake of CBP among patients with CD and comparing it
with a control population. METHODS: Eighty-two volunteers with CD and 77 non-CD
volunteers enrolled throughout Italy were asked to register their consumption of
CBP on specific diaries for three days. RESULTS: CD patients' median three-day
intake of biscuits and crackers was higher compared to controls (65.8 g vs. 22.7
g and 44.7 g vs. 10.6 g, p < 0.05 respectively, Mann-Whitney test). A significant
difference was observed also comparing the two groups for median three-day bread
consumption, with the CD group consuming less bread than controls (109.5 g vs.
150.7 g, p < 0.05, Mann-Whitney test). When assessing regional and gender-related
CBP consumption patterns, significantly higher rice consumption was found among
CD women from Northern Italy compared to CD women from Central and Southern Italy
(p = 0.006 and p = 0.002 respectively, Fisher's exact test). No other significant
differences were observed. CONCLUSIONS: Our results provide a snapshot of the
overall consumption of CBP among Italian subjects with CD. Altogether, these data
show that, despite minor differences, dietary consumption of CBP among CD
patients is similar to the general population.
PMID- 28420203
TI - Comments to Article by Solah VA et al., Nutrients 2017, 9, 149.
AB - n/a.
PMID- 28420205
TI - Do Chinese Children Get Enough Micronutrients?
AB - The aim of this study was to examine usual daily micronutrient intake of Chinese
children based on data from the 2011 China Health and Nutrition Survey. We
analyzed data from 4 to 17-year-old participants, who provided dietary data on
three consecutive days combined with the household weighing method in 2011. Usual
daily intake of each nutrient was estimated using a mixed effects model based on
the China Food Composition published in 2009. The means, medians and percentages
below Estimated Average Requirements (EAR) were reported for selected
micronutrients, including calcium, sodium, potassium, iron, zinc, selenium,
vitamin A, thiamine, riboflavin and vitamin C. For sodium and potassium, the
means and the distribution of intakes were compared to the Adequate Intake (AI)
level. The average usual daily intakes of all micronutrients increase with age,
and the intakes of boys were found to be higher than girls in the same age group.
The average calcium intake increased from 272 mg/day in 4-6 years to 391 mg/day
in 14-17 years, but the percentage of inadequate calcium intake remained very
high (>96%). The prevalence of inadequacy of calcium was the highest among the
mineral nutrients reported in this study. As the requirements of micronutrients
increased with age, the percentage of subjects with inadequate intake increased
in the 11-17 years age groups. Among 14-17 years group, the percentages of study
participants with dietary intakes of calcium, iron, zinc, selenium, vitamin A,
thiamine, riboflavin and vitamin C below the EAR were 96.8%, 18.8%, 37.6%, 72.8%,
36.8%, 91.8%. 85.9% and 75.5%, respectively. Among 11-13 years group, the
percentages of study participants with dietary intakes of iron, zinc and vitamin
A below the EAR were 23.5%, 41.5%, and 41.6%, respectively. Thus, micronutrient
deficiency is a problem in Chinese children. Nutrition education and intervention
programs are needed to address these nutritional gaps.
PMID- 28420204
TI - Fructose Intake, Serum Uric Acid, and Cardiometabolic Disorders: A Critical
Review.
AB - There is a direct relationship between fructose intake and serum levels of uric
acid (UA), which is the final product of purine metabolism. Recent preclinical
and clinical evidence suggests that chronic hyperuricemia is an independent risk
factor for hypertension, metabolic syndrome, and cardiovascular disease. It is
probably also an independent risk factor for chronic kidney disease, Type 2
diabetes, and cognitive decline. These relationships have been observed for high
serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to
high serum UA levels (5-6 mg/dL). In this regard, blood UA levels are much higher
in industrialized countries than in the rest of the world. Xanthine-oxidase
inhibitors can reduce UA and seem to minimize its negative effects on vascular
health. Other dietary and pathophysiological factors are also related to UA
production. However, the role of fructose-derived UA in the pathogenesis of
cardiometabolic disorders has not yet been fully clarified. Here, we critically
review recent research on the biochemistry of UA production, the relationship
between fructose intake and UA production, and how this relationship is linked to
cardiometabolic disorders.
PMID- 28420206
TI - The Status of Biofilms in Penile Implants.
AB - Erectile dysfunction is prevalent among men and will continue to become more so
with the aging population. Of the available treatment options, implantable
prosthetic devices are typically thought of as a third line treatment even though
they have the highest satisfaction rate and continually improving success rates.
Infection and mechanical failure are the most common reasons for implant revision
in the past. Since the development of more reliable devices, bacterial biofilms
are coming to the forefront of discussion as causes of required revision.
Biofilms are problematic as they are ubiquitous and exceedingly difficult to
prevent or treat.
PMID- 28420207
TI - TbetaRII Regulates the Proliferation of Metanephric Mesenchyme Cells through Six2
In Vitro.
AB - The transforming growth factor-beta (TGFbeta) family signaling pathways play an
important role in regulatory cellular networks and exert specific effects on
developmental programs during embryo development. However, the function of
TGFbeta signaling pathways on the early kidney development remains unclear. In
this work, we aim to detect the underlying role of TGFbeta type II receptor
(TbetaRII) in vitro, which has a similar expression pattern as the crucial
regulator Six2 during early kidney development. Firstly, the 5-ethynyl-2'
deoxyuridine (EdU) assay showed knock down of TbetaRII significantly decreased
the proliferation ratio of metanephric mesenchyme (MM) cells. Additionally, real
time Polymerase Chain Reaction (PCR) and Western blot together with
immunofluorescence determined that the mRNA and protein levels of Six2 declined
after TbetaRII knock down. Also, Six2 was observed to be able to partially rescue
the proliferation phenotype caused by the depletion of TbetaRII. Moreover,
bioinformatics analysis and luciferase assay indicated Smad3 could
transcriptionally target Six2. Further, the EdU assay showed that Smad3 could
also rescue the inhibition of proliferation caused by the knock down of TbetaRII.
Taken together, these findings delineate the important function of the TGFbeta
signaling pathway in the early development of kidney and TbetaRII was shown to be
able to promote the expression of Six2 through Smad3 mediating transcriptional
regulation and in turn activate the proliferation of MM cells.
PMID- 28420208
TI - Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer:
Systematic Review and Meta-Analysis.
AB - OBJECTIVE: To investigate the association between serum concentration of insulin
like growth factor (IGF) and the risk of pancreatic cancer (PaC). METHODS: We
identified eligible studies in Medline and EMBASE databases (no reference trials
from 2014 to 2016) in addition to the reference lists of original studies and
review articles on this topic. A summary of relative risks with 95% confidence
intervals (CI) was calculated using a random-effects model. The heterogeneity
between studies was assessed using Cochran Q and I2 statistics. RESULTS: Ten
studies (seven nested case-control studies and three retrospective case-control
studies) were selected as they met our inclusion criteria in this meta-analysis.
All these studies were published between 1997 and 2013. The current data
suggested that serum concentrations of IGF-I, IGF-II and insulin-like growth
factor binding protein-3 (IGFBP-3)in addition to the IGF-I/IGFBP-3 ratio were not
associated with an increased risk of PaC (Summary relative risks (SRRs) = 0.92,
95% CI: 0.67-1.16 for IGF-I; SRRs = 0.84, 95% CI: 0.54-1.15 for IGF-II; SRRs =
0.93, 95% CI: 0.69-1.17 for IGFBP-3; SRRs = 0.97, 95% CI: 0.71-1.23 for IGF
I/IGFBP-3 ratio). There was no publication bias in the present meta-analysis.
CONCLUSION: Serum concentrations of IGF-I, IGF-II, IGFBP-1 and IGFBP-3 as well as
the IGF-I/IGFBP-3 ratio were not associated with increased risk of PaC.
PMID- 28420209
TI - Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase
in Pregnant Women.
AB - Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD)
activity are considered biomarkers of lead exposure and lead toxicity,
respectively. The present study was designed to investigate the association
between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of
633 pregnant women aged 13-43 years participated in this study. Blood lead was
measured by a graphite furnace atomic absorption spectrometer. ALAD activity was
measured spectrophotometrically. Mean blood lead was 2.09 +/- 2.34 ug/dL; and 26
women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5
ug/dL. ALAD activity was significantly lower in women with levels of lead >=5
ug/dL compared to those with BLLs < 5 ug/dL (p = 0.002). To reduce the influence
of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A
significant negative correlation between blood lead and ALAD activity was
observed in the fourth quartile of BLLs (r = -0.113; p < 0.01). Among women with
blood lead concentrations >=2.2 ug/dL ALAD activity was negatively correlated
with BLLs (r = -0.413; p < 0.01). Multiple linear regression demonstrated that
inhibition of ALAD in pregnant women may occur at levels of lead in blood above
2.2 ug/dL.
PMID- 28420210
TI - Predictors of Active Extravasation and Complications after Conventional
Angiography for Acute Intraabdominal Bleeding.
AB - Conventional angiography is used to evaluate and treat possible sources of
intraabdominal bleeding, though it may cause complications such as contrast
induced nephropathy (CIN). The study's purpose was to identify factors predicting
active extravasation and complications during angiography for acute
intraabdominal bleeding. All conventional angiograms for acute bleeding (January
2013-June 2015) were reviewed retrospectively, including 75 angiograms for
intraabdominal bleeding in 70 patients. Demographics, comorbidities, vital signs,
complications within one month, and change in hematocrit (DeltaHct) and fluids
and blood products administered over the 24 h prior to angiography were recorded.
Of 75 exams, 20 (27%) demonstrated extravasation. DeltaHct was the only
independent predictor of extravasation (p = 0.017), with larger DeltaHct (-17%)
in patients with versus those without extravasation (-1%) (p = 0.01). CIN was the
most common complication, occurring in 10 of 66 angiograms (15%). Glomerular
filtration rate (GFR) was the only independent predictor (p = 0.03); 67% of
patients with GFR < 30, 29% of patients with GFR 30-60, and 8% of patients with
GFR > 60 developed CIN. For patients with intraabdominal bleeding, greater
DeltaHct decrease over 24 h before angiography predicts active extravasation. Pre
existing renal impairment predicts CIN. Patients with large hematocrit declines
should be triaged for rapid angiography, though benefits can be weighed with the
risk of renal impairment.
PMID- 28420211
TI - Cognitive Remediation Therapy for Adolescents with Anorexia Nervosa-Treatment
Satisfaction and the Perception of Change.
AB - Cognitive remediation therapy (CRT) has recently been developed for children and
adolescents with anorexia nervosa (AN). It focuses on decreasing rigid cognitions
and behaviors, as well as increasing central coherence. Overall, CRT has been
proven feasible for young individuals with AN, but little is known regarding the
specifics of its feasibility, and the perception of change associated with the
intervention. Consequently, the aim of the current study was to explore service
users' perspective on CRT with a specific focus on treatment delivery, treatment
content, and perceived change. Twenty adolescents (age 13-18) with AN
participated in a 10-session course of CRT. A 20-item treatment evaluation
questionnaire was administered at the end of treatment, focusing on four aspects
of the intervention: (1) general attitudes towards treatment, (2) treatment
specifics, (3) the perception of change and (4) the patient-therapist relation.
The main findings suggest high levels of treatment satisfaction, but somewhat
limited perceptions of change. The current study is one of the most detailed
accounts of adolescents' perspective on CRT published on eating disorders, and
highlights several important aspects of the treatment viewed through the eye of
the receiver.
PMID- 28420212
TI - Nutritional Status Predicts 10-Year Mortality in Patients with End-Stage Renal
Disease on Hemodialysis.
AB - Protein-energy wasting (PEW) is associated with mortality in patients with end
stage renal disease (ESRD) on maintenance hemodialysis. The correct diagnosis of
PEW is extremely important in order to predict clinical outcomes. However, it is
unclear which parameters should be used to diagnose PEW. Therefore, this
retrospective observational study investigated the relationship between mortality
and nutritional parameters in ESRD patients on maintenance hemodialysis. A total
of 144 patients were enrolled. Nutritional parameters, including body mass index,
serum albumin, dietary intake, normalized protein catabolic rate (nPCR), and
malnutrition inflammation score (MIS), were measured at baseline. Fifty-three
patients died during the study. Survivors had significantly higher nPCR (1.10 +/-
0.24 g/kg/day vs. 1.01 +/- 0.21 g/kg/day; p = 0.048), energy intake (26.7 +/- 5.8
kcal/kg vs. 24.3 +/- 4.2 kcal/kg; p = 0.009) and protein intake (0.91 +/- 0.21
g/kg vs. 0.82 +/- 0.24 g/kg; p = 0.020), and lower MIS (5.2 +/- 2.3 vs. 6.1 +/-
2.1, p = 0.039). In multivariable analysis, energy intake <25 kcal/kg (HR 1.860,
95% CI 1.018-3.399; p = 0.044) and MIS > 5 (HR 2.146, 95% CI 1.173-3.928; p =
0.013) were independent variables associated with all-cause mortality. These
results suggest that higher MIS and lower energy intake are harmful to ESRD
patients on maintenance hemodialysis. Optimal energy intake could reduce
mortality in these patients.
PMID- 28420213
TI - Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for
Targeting Retinoblastoma.
AB - The aim of this study was to develop a novel folate receptor-targeted drug
delivery system for retinoblastoma cells using a promising anticancer agent,
curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used
as a targeting moiety to enhance the targeting and bioavailability of CDF. For
this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA
FA) was synthesized and utilized to improve the aqueous solubility of a highly
hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery
to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and
characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition
(HPLC) for estimating CDF was determined and validated. The formulation was
optimized to achieve maximum entrapment of CDF. The particle size of the micelles
was measured and confirmed by dynamic light scattering (DLS) and transmission
electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI
RB) retinoblastoma cells. Results showed that the solubility of CDF could be
increased with the newly-synthesized polymer, and the entrapment efficiency was
>85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a
narrow size distribution. The formulation did not show any adverse cytotoxicity
on a human retinal pigment epithelial cell (ARPE-19), indicating its safety.
However, it showed significant cell killing activity in both Y-79 and WERI-RB
retinoblastoma cell lines, indicating its potency in killing cancer cells. In
conclusion, the folic acid-conjugated SMA loaded with CDF showed promising
potential with high safety and pronounced anticancer activity on the tested
retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could
be a viable option as an alternative approach to current retinoblastoma
therapies.
PMID- 28420214
TI - Multi-Mode Estimation for Small Fixed Wing Unmanned Aerial Vehicle Localization
Based on a Linear Matrix Inequality Approach.
AB - Information fusion from multiple sensors ensures the accuracy and robustness of a
navigation system, especially in the absence of global positioning system (GPS)
data which gets degraded in many cases. A way to deal with multi-mode estimation
for a small fixed wing unmanned aerial vehicle (UAV) localization framework is
proposed, which depends on utilizing a Luenberger observer-based linear matrix
inequality (LMI) approach. The proposed estimation technique relies on the
interaction between multiple measurement modes and a continuous observer. The
state estimation is performed in a switching environment between multiple active
sensors to exploit the available information as much as possible, especially in
GPS-denied environments. Luenberger observer-based projection is implemented as a
continuous observer to optimize the estimation performance. The observer gain
might be chosen by solving a Lyapunov equation by means of a LMI algorithm.
Convergence is achieved by utilizing the linear matrix inequality (LMI), based on
Lyapunov stability which keeps the dynamic estimation error bounded by selecting
the observer gain matrix (L). Simulation results are presented for a small UAV
fixed wing localization problem. The results obtained using the proposed approach
are compared with a single mode Extended Kalman Filter (EKF). Simulation results
are presented to demonstrate the viability of the proposed strategy.
PMID- 28420215
TI - A Phonocardiographic-Based Fiber-Optic Sensor and Adaptive Filtering System for
Noninvasive Continuous Fetal Heart Rate Monitoring.
AB - This paper focuses on the design, realization, and verification of a novel
phonocardiographic- based fiber-optic sensor and adaptive signal processing
system for noninvasive continuous fetal heart rate (fHR) monitoring. Our proposed
system utilizes two Mach-Zehnder interferometeric sensors. Based on the analysis
of real measurement data, we developed a simplified dynamic model for the
generation and distribution of heart sounds throughout the human body. Building
on this signal model, we then designed, implemented, and verified our adaptive
signal processing system by implementing two stochastic gradient-based
algorithms: the Least Mean Square Algorithm (LMS), and the Normalized Least Mean
Square (NLMS) Algorithm. With this system we were able to extract the fHR
information from high quality fetal phonocardiograms (fPCGs), filtered from
abdominal maternal phonocardiograms (mPCGs) by performing fPCG signal peak
detection. Common signal processing methods such as linear filtering, signal
subtraction, and others could not be used for this purpose as fPCG and mPCG
signals share overlapping frequency spectra. The performance of the adaptive
system was evaluated by using both qualitative (gynecological studies) and
quantitative measures such as: Signal-to-Noise Ratio-SNR, Root Mean Square Error
RMSE, Sensitivity-S+, and Positive Predictive Value-PPV.
PMID- 28420216
TI - Fast Bragg Grating Inscription in PMMA Polymer Optical Fibres: Impact of Thermal
Pre-Treatment of Preforms.
AB - In this work, fibre Bragg gratings (FBGs) were inscribed in two different undoped
poly- (methyl methacrylate) (PMMA) polymer optical fibres (POFs) using different
types of UV lasers and their inscription times, temperature and strain
sensitivities are investigated. The POF Bragg gratings (POFBGs) were inscribed
using two UV lasers: a continuous UV HeCd @325 nm laser and a pulsed UV KrF @248
nm laser. Two PMMA POFs are used in which the primary and secondary preforms
(during the two-step drawing process) have a different thermal treatment. The
PMMA POFs drawn in which the primary or secondary preform is not specifically pre
treated need longer inscription time than the fibres drawn where both preforms
have been pre-annealed at 80 degrees C for 2 weeks. Using both UV lasers, for
the latter fibre much less inscription time is needed compared to another
homemade POF. The properties of a POF fabricated with both preforms thermally
well annealed are different from those in which just one preform step process is
thermally treated, with the first POFs being much less sensitive to thermal
treatment. The influence of annealing on the strain and temperature sensitivities
of the fibres prior to FBG inscription is also discussed, where it is observed
that the fibre produced from a two-step drawing process with well-defined pre
annealing of both preforms did not produce any significant difference in
sensitivity. The results indicate the impact of preform thermal pre-treatment
before the PMMA POFs drawing, which can be an essential characteristic in the
view of developing POF sensors technology.
PMID- 28420217
TI - Microfluidic EBG Sensor Based on Phase-Shift Method Realized Using 3D Printing
Technology.
AB - In this article, we propose a novel microfluidic microstrip electromagnetic band
gap (EBG) sensor realized using cost-effective 3D printing technology. Microstrip
sensor allows monitoring of the fluid properties flowing in the microchannel
embedded between the microstrip line and ground plane. The sensor's operating
principle is based on the phase-shift method, which allows the characterization
at a single operating frequency of 6 GHz. The defected electromagnetic band gap
(EBG) structure is realized as a pattern in the microstrip ground plane to
improve sensor sensitivity. The designed microfluidic channel is fabricated using
a fused deposition modelling (FDM) 3D printing process without additional
supporting layers, while the conductive layers are realized using sticky
aluminium tape. The measurement results show that the change of permittivity of
the fluid in the microfluidic channel from 1 to 80 results in the phase-shift
difference of almost 90 degrees . The potential application is demonstrated
through the implementation of a proposed sensor for the detection of toluene
concentration in toluene-methanol mixture where various concentrations of toluene
were analysed.
PMID- 28420218
TI - A Latency and Coverage Optimized Data Collection Scheme for Smart Cities Based on
Vehicular Ad-hoc Networks.
AB - Using mobile vehicles as "data mules" to collect data generated by a huge number
of sensing devices that are widely spread across smart city is considered to be
an economical and effective way of obtaining data about smart cities. However,
currently most research focuses on the feasibility of the proposed methods
instead of their final performance. In this paper, a latency and coverage
optimized data collection (LCODC) scheme is proposed to collect data on smart
cities through opportunistic routing. Compared with other schemes, the efficiency
of data collection is improved since the data flow in LCODC scheme consists of
not only vehicle to device transmission (V2D), but also vehicle to vehicle
transmission (V2V). Besides, through data mining on patterns hidden in the smart
city, waste and redundancy in the utilization of public resources are mitigated,
leading to the easy implementation of our scheme. In detail, no extra supporting
device is needed in the LCODC scheme to facilitate data transmission. A large
scale and real-world dataset on Beijing is used to evaluate the LCODC scheme.
Results indicate that with very limited costs, the LCODC scheme enables the
average latency to decrease from several hours to around 12 min with respect to
schemes where V2V transmission is disabled while the coverage rate is able to
reach over 30%.
PMID- 28420219
TI - Integrated Flexible Electronic Devices Based on Passive Alignment for
Physiological Measurement.
AB - This study proposes a simple method of fabricating flexible electronic devices
using a metal template for passive alignment between chip components and an
interconnect layer, which enabled efficient alignment with high accuracy. An
electrocardiogram (ECG) sensor was fabricated using 20 um thick polyimide (PI)
film as a flexible substrate to demonstrate the feasibility of the proposed
method. The interconnect layer was fabricated by a two-step photolithography
process and evaporation. After applying solder paste, the metal template was
placed on top of the interconnect layer. The metal template had rectangular holes
at the same position as the chip components on the interconnect layer.
Rectangular hole sizes were designed to account for alignment tolerance of the
chips. Passive alignment was performed by simply inserting the components in the
holes of the template, which resulted in accurate alignment with positional
tolerance of less than 10 um based on the structural design, suggesting that our
method can efficiently perform chip mounting with precision. Furthermore, a
fabricated flexible ECG sensor was easily attachable to the curved skin surface
and able to measure ECG signals from a human subject. These results suggest that
the proposed method can be used to fabricate epidermal sensors, which are mounted
on the skin to measure various physiological signals.
PMID- 28420220
TI - The Maximal C3 Self-Complementary Trinucleotide Circular Code X in Genes of
Bacteria, Archaea, Eukaryotes, Plasmids and Viruses.
AB - In 1996, a set X of 20 trinucleotides was identified in genes of both prokaryotes
and eukaryotes which has on average the highest occurrence in reading frame
compared to its two shifted frames. Furthermore, this set X has an interesting
mathematical property as X is a maximal C 3 self-complementary trinucleotide
circular code. In 2015, by quantifying the inspection approach used in 1996, the
circular code X was confirmed in the genes of bacteria and eukaryotes and was
also identified in the genes of plasmids and viruses. The method was based on the
preferential occurrence of trinucleotides among the three frames at the gene
population level. We extend here this definition at the gene level. This new
statistical approach considers all the genes, i.e., of large and small lengths,
with the same weight for searching the circular code X . As a consequence, the
concept of circular code, in particular the reading frame retrieval, is directly
associated to each gene. At the gene level, the circular code X is strengthened
in the genes of bacteria, eukaryotes, plasmids, and viruses, and is now also
identified in the genes of archaea. The genes of mitochondria and chloroplasts
contain a subset of the circular code X . Finally, by studying viral genes, the
circular code X was found in DNA genomes, RNA genomes, double-stranded genomes,
and single-stranded genomes.
PMID- 28420221
TI - A Narrative Review: Actigraphy as an Objective Assessment of Perioperative Sleep
and Activity in Pediatric Patients.
AB - Sleep is an important component of pediatric health and is crucial for cognitive
development. Actigraphy is a validated, objective tool to capture sleep and
movement data that is increasingly being used in the perioperative context. The
aim of this review is to present recent pediatric studies that utilized
actigraphy in the perioperative period, highlight gaps in the literature, and
provide recommendations for future research. A literature search was completed
using OVID and PubMed databases and articles were selected for inclusion based on
relevance to the topic. The literature search resulted in 13 papers that utilized
actigraphic measures. Results of the review demonstrated that actigraphy has been
used to identify predictors and risk factors for poor postoperative sleep,
examine associations among perioperative pain and sleep patterns, and assess
activity and energy expenditure in both inpatient and outpatient settings. We
propose expansion of actigraphy research to include assessment of sleep via
actigraphy to: predict functional recovery in pediatric populations, to study
postoperative sleep in high-risk pediatric patients, to test the efficacy of
perioperative interventions, and to assess outcomes in special populations for
which self-report data on sleep and activity is difficult to obtain.
PMID- 28420222
TI - How Sensors Might Help Define the External Exposome.
AB - The advent of the exposome concept, the advancement of mobile technology,
sensors, and the "internet of things" bring exciting opportunities to exposure
science. Smartphone apps, wireless devices, the downsizing of monitoring
technologies, along with lower costs for such equipment makes it possible for
various aspects of exposure to be measured more easily and frequently. We discuss
possibilities and lay out several criteria for using smart technologies for
external exposome studies. Smart technologies are evolving quickly, and while
they provide great promise for advancing exposure science, many are still in
developmental stages and their use in epidemiology and risk studies must be
carefully considered. The most useable technologies for exposure studies at this
time relate to gathering exposure-factor data, such as location and activities.
Development of some environmental sensors (e.g., for some air pollutants, noise,
UV) is moving towards making the use of these more reliable and accessible to
research studies. The possibility of accessing such an unprecedented amount of
personal data also comes with various limitations and challenges, which are
discussed. The advantage of improving the collection of long term exposure factor
data is that this can be combined with more "traditional" measurement data to
model exposures to numerous environmental factors.
PMID- 28420223
TI - Clinical and Molecular Characterization of Patients with Fructose 1,6
Bisphosphatase Deficiency.
AB - Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, autosomal recessive
inherited disease caused by the mutation of the FBP1 gene, the incidence is
estimated to be between 1/350,000 and 1/900,000. The symptoms of affected
individuals are non-specific and are easily confused with other metabolic
disorders. The present study describes the clinical features of four Chinese
pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic
acidosis, and hyperuricemia. Targeted-next generation sequencing using the
Agilent SureSelect XT Inherited Disease Panel was used to screen for causal
variants in the genome, and the clinically-relevant variants were subsequently
verified using Sanger sequencing. Here, DNA sequencing identified six variations
of the FBP1 gene (NM_000507.3) in the four patients. In Case 1, we found a
compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42) (novel) and
c.960_961insG (p.Ser321Valfs) (known pathogenic). In Case 2, we found a compound
heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known
pathogenically). In Case 3, a homozygous missense mutation of c.355G>A
(p.Asp119Asn) (reported in ClinVar database without functional study) was found.
Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33)
(novel) and c.490G>A (p.Gly164Ser) (known pathogenically). Further in vitro
studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no
impact on protein expression, but decreased the enzyme activity, and with which
the clinical significance of Asp119Asn can be determined to be likely pathogenic.
This report not only expands upon the known spectrum of variation of the FBP1
gene, but also deepens our understanding of the clinical features of FBPase
deficiency.
PMID- 28420224
TI - Silk Fibroin-Alginate-Hydroxyapatite Composite Particles in Bone Tissue
Engineering Applications In Vivo.
AB - The aim of this study was to evaluate the in vivo bone regeneration capability of
alginate (AL), AL/hydroxyapatite (HA), and AL/HA/silk fibroin (SF) composites.
Forty Sprague Dawley rats were used for the animal experiments. Central calvarial
bone (diameter: 8.0 mm) defects were grafted with AL, AL/HA, or AL/HA/SF. New
bone formation was evaluated by histomorphometric analysis. To demonstrate the
immunocompatibility of each group, the level of tumor necrosis factor (TNF)-alpha
expression was studied by immunohistochemistry (IHC) and quantitative reverse
transcription polymerase chain reaction (qRT-PCR) at eight weeks post
implantation. Additionally, osteogenic markers, such as fibroblast growth factor
(FGF)-23, osteoprotegerin (OPG), and Runt-related transcription factor (Runx2)
were evaluated by qPCR or IHC at eight weeks post implantation. The AL/HA/SF
group showed significantly higher new bone formation than did the control group
(p = 0.044) and the AL group (p = 0.035) at four weeks post implantation.
Additionally, the AL/HA/SF group showed lower relative TNF-alpha mRNA levels and
higher FGF-23 mRNA levels than the other groups did at eight weeks post
implantation. IHC results demonstrated that the AL/HA/SF group had lower TNF
alpha expression and higher OPG and Runx2 expression at eight weeks post
implantation. Additionally, no evidence of the inflammatory reaction or giant
cell formation was observed around the residual graft material. We concluded that
the AL/HA/SF composite could be effective as a scaffold for bone tissue
engineering.
PMID- 28420226
TI - Determination of Magnetic Parameters of Maghemite (gamma-Fe2O3) Core-Shell
Nanoparticles from Nonlinear Magnetic Susceptibility Measurements.
AB - Method of determining of magnetic moment and size from measurements of dependence
of the nonlinear magnetic susceptibility upon magnetic field is proposed,
substantiated and tested for superparamagnetic nanoparticles (SPNP) of the
"magnetic core-polymer shell" type which are widely used in biomedical
technologies. The model of the induction response of the SPNP ensemble on the
combined action of the magnetic harmonic excitation field and permanent bias
field is built, and the analysis of possible ways to determine the magnetic
moment and size of the nanoparticles as well as the parameters of the
distribution of these variables is performed. Experimental verification of the
proposed method was implemented on samples of SPNP with maghemite core in dry
form as well as in colloidal systems. The results have been compared with the
data obtained by other methods. Advantages of the proposed method are analyzed
and discussed, particularly in terms of its suitability for routine express
testing of SPNP for biomedical technology.
PMID- 28420225
TI - Engineering the Complex-Valued Constitutive Parameters of Metamaterials for
Perfect Absorption.
AB - We theoretically studied how to directly engineer the constitutive parameters of
metamaterials for perfect absorbers of electromagnetic waves. As an example, we
numerically investigated the necessary refractive index n and extinction
coefficient k and the relative permittivity epsilon and permeability MU of a
metamaterial anti-reflection layer, which could cancel the reflection from a
hydrogenated amorphous silicon (alpha-Si:H) thin film on a metal substrate,
within the visible wavelength range from 300 to 800 nm. We found that the
metamaterial anti-reflection layer should have a negative refractive index (n <
0) for short-wavelength visible light but have a positive refractive index (n >
0) for long-wavelength visible light. The relative permittivity epsilon and
permeability MU could be fitted by the Lorentz model, which exhibited electric
and magnetic resonances, respectively.
PMID- 28420227
TI - Efficacy and tolerability of a plant-based, multi-component cream (Ginetrox(r))
in vulvovaginal disorders of the genitourinary syndrome during menopause.
AB - BACKGROUND: Genitourinary syndrome of menopause (GSM) is a symptomatic condition
including vaginal dryness, irritation, dyspareunia and recurrent urinary tract
infections which affects 40-54% of post-menopausal women. Although several
estrogen-based therapies are available, it is generally preferable to avoid
hormonal therapy, particularly in women with mild symptoms or at risk for
estrogen-responsive neoplasia. Therefore, the most common treatment options are
over-the-counter vaginal creams for symptomatic relief. METHODS: Thirty-three
postmenopausal women suffering from GSM were enrolled in this observational
study. A multi-component cream (Ginetrox(r), Indena, Milan, Italy) was applied on
the vestibular area of the vagina for three months. The primary endpoints were:
vaginal burning and/or pain, assessed by Visual Analog Scale and dyspareunia,
assessed using the Marinoff Score. As a secondary endpoint, vestibular health was
evaluated through a four-point scale. Side effects and adherence to treatment
were also recorded. RESULTS: Statistically significant improvement was observed
in pain scores and dyspareunia at the end of the treatment compared to baseline
values. The vestibular health index significantly decreased after 3 months.
Tolerability was acceptable. CONCLUSIONS: This preliminary study suggests that
the plant-based, multi-component cream Ginetrox(r) could be effective and safe in
counteracting menopause-related vaginal discomfort symptoms.
PMID- 28420228
TI - Influence of Order within Nonpolar Monolayers on Hydrophobic Interactions.
AB - We report an experimental investigation of the influence of molecular-level order
(crystallinity) within nonpolar monolayers on hydrophobic interactions. The
measurements were performed using gold film-supported monolayers formed from
alkanethiols (CH3(CH2)nSH, with n ranging from 3 to 17), which we confirmed by
using polarization-modulation infrared reflection-adsorption spectroscopy to
exhibit chain-length-dependent order (methylene peak moves from 2926 to 2919 cm
1, corresponding to a transition from liquid- to quasi-crystalline-like order) in
the absence of substantial changes in chain density (constant methyl peak
intensity). By using monolayer-covered surfaces immersed in either aqueous
triethanolamine (TEA, 10 mM, pH 7.0) or pure methanol, we quantified hydrophobic
and van der Waals contributions to adhesive interactions between identical pairs
of surfaces (measured using an atomic force microscope) as a function of the
length and order of the aliphatic chains within the monolayers. In particular, we
measured pull-off forces arising from hydrophobic adhesion to increase in a
nonlinear manner with chain length (abrupt increase between n = 5 and 6 from 2.1
+/- 0.3 to 14.1 +/- 0.7 nN) and to correlate closely with a transition from a
liquid-like to crystalline-like monolayer phase. In contrast, adhesion in
methanol increased gradually with chain length from 0.3 +/- 0.1 to 3.2 +/- 0.3 nN
for n = 3 to 7 and then did not change further with an increase in chain length.
These results lead to the hypothesis that order within nonpolar monolayers
influences hydrophobic interactions. Additional support for this hypothesis was
obtained from measurements reported in this paper using long-chain alkanethiols
(ordered) and alkenethiols (disordered). The results are placed into the context
of recent spectroscopic studies of hydrogen bonding of water at nonpolar
monolayers. Overall, our study provides new insight into factors that influence
hydrophobic interactions at nonpolar monolayers.
PMID- 28420229
TI - High-Affinity Copolymers Inhibit Digestive Enzymes by Surface Recognition.
AB - This account presents a general method for the construction of polymeric surface
binders for digestion enzymes. Two prominent parts, namely, the modification of
the copolymer composition and the screening assay for the most powerful
inhibitors are both amenable to parallelization. The concept hinges on the
appropriate selection of amino-acid-selective comonomers, their free radical
copolymerization, and subsequent screening of the resulting copolymer library for
efficient enzyme inhibition. A microscale synthetic procedure for the
copolymerization process was developed, which produces water-soluble affinity
polymers that can be stored for years at room temperature. Initial parallel
screening was conducted in standard enzyme assays to identify polymeric
inhibitors, which were subsequently subjected to determination of IC50 values for
their target enzyme. For all digestion enzymes, except elastase, a number of
polymer inhibitors were found, some of which were selective toward one or two
protein targets. Since the key monomers of the best inhibitors bind to amino acid
residues in the direct vicinity of the active site, we conclude that efficient
coverage of the immediate environment by the copolymers is critical. Strong
interference with enzymatic activity is brought about by blocking the substrate
access and product exit to and from the active site.
PMID- 28420230
TI - An Unambiguous Nomenclature for the Acyl-quinic Acids Commonly Known as
Chlorogenic Acids.
AB - The history of the acyl-quinic acids is briefly reviewed, the merits and
limitations of the various nomenclature systems applicable are critically
compared, and their limitations are highlighted, in particular their inability to
provide an unambiguous description of all quinic acid enantiomers and
diastereoisomers and associated acyl-quinic acids. Recommendations are made for a
nomenclature system that in combination with IUPAC numbering achieves this
objective. A comprehensive set of structures for the quinic acid enantiomers and
diastereoisomers is presented. The Supporting Information provides an explanation
of trivial names and a decision tree to determine which quinic acid isomer a
structure represents.
PMID- 28420231
TI - Biological Control of Aflatoxin Contamination in U.S. Crops and the Use of
Bioplastic Formulations of Aspergillus flavus Biocontrol Strains To Optimize
Application Strategies.
AB - Aflatoxin contamination has a major economic impact on crop production in the
southern United States. Reduction of aflatoxin contamination in harvested crops
has been achieved by applying nonaflatoxigenic biocontrol Aspergillus flavus
strains that can out-compete wild aflatoxigenic A. flavus, reducing their numbers
at the site of application. Currently, the standard method for applying
biocontrol A. flavus strains to soil is using a nutrient-supplying carrier (e.g.,
pearled barley for Afla-Guard). Granules of Bioplastic (partially acetylated corn
starch) have been investigated as an alternative nutritive carrier for biocontrol
agents. Bioplastic granules have also been used to prepare a sprayable biocontrol
formulation that gives effective reduction of aflatoxin contamination in
harvested corn kernels with application of much smaller amounts to leaves later
in the growing season. The ultimate goal of biocontrol research is to produce
biocontrol systems that can be applied to crops only when long-range weather
forecasting indicates they will be needed.
PMID- 28420232
TI - Gas-Phase Carboxylic Acids in a University Classroom: Abundance, Variability, and
Sources.
AB - Gas-phase carboxylic acids are ubiquitous in ambient air, yet their indoor
occurrence and abundance are poorly characterized. To fill this gap, we measured
gas-phase carboxylic acids in real-time inside and outside of a university
classroom using a high-resolution time-of-flight chemical ionization mass
spectrometer (HRToF-CIMS) equipped with an acetate ion source. A wide variety of
carboxylic acids were identified indoors and outdoors, including monoacids,
diacids, hydroxy acids, carbonyl acids, and aromatic acids. An empirical
parametrization was derived to estimate the sensitivity (ion counts per ppt of
the analytes) of the HRToF-CIMS to the acids. The campaign-average concentration
of carboxylic acids measured outdoors was 1.0 ppb, with the peak concentration
occurring in daytime. The average indoor concentration of carboxylic acids was
6.8 ppb, of which 87% was contributed by formic and lactic acid. While carboxylic
acids measured outdoors displayed a single daytime peak, those measured indoors
displayed a daytime and a nighttime peak. Besides indoor sources such as off
gassing of building materials, evidence for acid production from indoor chemical
reactions with ozone was found. In addition, some carboxylic acids measured
indoors correlated to CO2 in daytime, suggesting that human occupants may
contribute to their abundance either through direct emissions or surface
reactions.
PMID- 28420233
TI - Novel Hydrogen-Bonding Cross-Linking Aggregation-Induced Emission: Water as a
Fluorescent "Ribbon" Detected in a Wide Range.
AB - The development of efficient sensors for detection of the water content in a wide
detection range is highly desirable for balance in many industrial processes and
products. Presented herein are six novel different substituted Schiff base Zn(II)
complexes, which exhibit the remarkable capability to detect traces of water in a
wide linear range (most can reach 0-94%, v/v), low detection limit of 0.2% (v/v),
and rapid response time of 8 s in various organic solvents by virtue of an
unusual water-activated hydrogen-bonding cross-linking AIE (WHCAIE) mechanism. As
a proof-of-concept, the WHCAIE mechanism is explained well by single X-ray
diffraction, absorption spectra, fluorescence spectra, dynamic light scattering,
1H NMR spectra, and theoretical calculations. In addition, the molecules
demonstrated their application for the detection of humidity (42-80%). These
Schiff base Zn(II) complexes become one of the most powerful water sensors known
due to their extraordinary sensitivity, fast response, and wide detection range
for water.
PMID- 28420234
TI - Raman Spectroscopy of Fish Oil Capsules: Polyunsaturated Fatty Acid Quantitation
Plus Detection of Ethyl Esters and Oxidation.
AB - Fish oils are the primary dietary source of omega-3 polyunsaturated fatty acids
(PUFA), but these compounds are prone to oxidation, and commercial fish oil
supplements sometimes contain less PUFA than claimed. These supplements are
predominantly sold in softgel capsules. In this work, we show that Fourier
transform (FT)-Raman spectra of fish oils (n = 5) and omega-3 PUFA concentrates
(n = 6) can be acquired directly through intact softgel (gelatin) capsules. These
spectra could be used to rapidly distinguish supplements containing ethyl esters
from those containing triacylglyceride oils. Raman spectroscopy calibrated with
partial least-squares regression against traditional fatty acid methyl ester
analyses by gas chromatography-mass spectrometry could be used to rapidly and
nondestructively quantitate PUFA and other fatty acid classes directly though
capsules. We also show that FT-Raman spectroscopy can noninvasively detect
oxidation with high sensitivity. Oils with peroxide values of as low as 10 mequiv
kg-1, which are on the cusp of falling outside of specification, could be readily
distinguished from oils that were within specification (7 mequiv kg-1).
PMID- 28420235
TI - Garcinol from Garcinia indica Downregulates Cancer Stem-like Cell Biomarker
ALDH1A1 in Nonsmall Cell Lung Cancer A549 Cells through DDIT3 Activation.
AB - Nonsmall cell lung cancer (NSCLC) is the predominant type of lung cancer.
Patients with NSCLC show high mortality rates because of failure to clean up
cancer stem cells (CSCs). The anticancer activity of phytochemical garcinol has
been identified in various cancer cell models. However, the effect of garcinol on
NSCLC cell lines is still lacking. Of the NSCLC cell lines we tested, A549 cells
were the most sensitive to garcinol. Interestingly, Aldehyde Dehydrogenase 1
Family Member A1 (ALDH1A1) was preferentially expressed in A549 cells and
downregulated by the addition of garcinol. We also found that garcinol enriched
DNA damage-inducible transcript 3 (DDIT3) and then altered DDIT3-CCAAT-enhancer
binding proteins beta (C/EBPbeta) interaction resulting in a decreased binding of
C/EBPbeta to the endogenous ALDH1A1 promoter. Furthermore, garcinol's inhibition
of ALDH1A1 was identified in a xenograft mice model. Garcinol repressed ALDH1A1
transcription in A549 cells through alterations in the interaction between DDIT3
and C/EBPbeta. Garcinol could be a potential dietary phytochemical candidate for
NSCLCs patients whose tumors harbored high ALDH1A1 expression.
PMID- 28420236
TI - Human Hepatocarcinoma Cell Targeting by Glypican-3 Ligand Peptide Functionalized
Silica Nanoparticles: Implications for Ultrasound Molecular Imaging.
AB - Silica nanoparticles (SiNPs) are widely studied nanomaterials for their potential
employment in advanced biomedical applications, such as selective molecular
imaging and targeted drug delivery. SiNPs are generally low cost and highly
biocompatible, can be easily functionalized with a wide variety of functional
ligands, and have been demonstrated to be effective in enhancing ultrasound
contrast at clinical diagnostic frequencies. Therefore, SiNPs might be used as
contrast agents in echographic imaging. In this work, we have developed a SiNPs
based system for the in vitro molecular imaging of hepatocellular carcinoma cells
that express high levels of glypican-3 protein (GPC-3) on their surface. In this
regard, a novel GPC-3 targeting peptide was designed and conjugated to
fluorescent silica nanoparticles. The physicochemical properties, acoustic
behavior, and biocompatibility profile of the functionalized SiNPs were
characterized; then binding and uptake of both naked and functionalized SiNPs
were analyzed by laser scanning confocal microscopy and transmission electron
microscopy in GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. The
results obtained showed that GPC-3-functionalized fluorescent SiNPs significantly
enhanced the ultrasound contrast and were effectively bound and taken up by HepG2
cells without affecting their viability.
PMID- 28420237
TI - Intrinsic Instability of Cs2In(I)M(III)X6 (M = Bi, Sb; X = Halogen) Double
Perovskites: A Combined Density Functional Theory and Experimental Study.
AB - Recently, there has been substantial interest in developing double-B-cation
halide perovskites, which hold the potential to overcome the toxicity and
instability issues inherent within emerging lead halide-based solar absorber
materials. Among all double perovskites investigated, In(I)-based Cs2InBiCl6 and
Cs2InSbCl6 have been proposed as promising thin-film photovoltaic absorber
candidates, with computational examination predicting suitable materials
properties, including direct bandgap and small effective masses for both
electrons and holes. In this study, we report the intrinsic instability of
Cs2In(I)M(III)X6 (M = Bi, Sb; X = halogen) double perovskites by a combination of
density functional theory and experimental study. Our results suggest that the
In(I)-based double perovskites are unstable against oxidation into In(III)-based
compounds. Further, the results show the need to consider reduction-oxidation
(redox) chemistry when predicting stability of new prospective electronic
materials, especially when less common oxidation states are involved.
PMID- 28420238
TI - The Role of Ti Buffer Layer Thickness on the Resistive Switching Properties of
Hafnium Oxide-Based Resistive Switching Memories.
AB - Ti/HfOx-based resistive random access memory (RRAM) has been extensively
investigated as an emerging nonvolatile memory (NVM) candidate due to its
excellent memory performance and CMOS process compatibility. Although the
importance of the role of the Ti buffer layer is well recognized, detailed
understanding about the nature of Ti thickness-dependent asymmetric switching is
still missing. To realize this, the present work addresses the effects of Ti
buffer layer thickness on the switching properties of TiN/Ti/HfOx/TiN 1T1R RRAM.
Consequently, we have demonstrated a simple strategy to regulate the FORMING
voltage, leakage current, memory window, and decrease the operation current, etc.
by varying the thickness of the Ti layer on the HfOx dielectrics. Accordingly,
controllable and reliable bipolar, complementary, and reverse bipolar resistive
switching (BRS, CRS, and R-BRS) properties have been demonstrated. This work also
provides the direction to avoid unwanted CRS properties during the first RESET
operation by decreasing the FORMING voltage. Furthermore, the memory device shows
good nonvolatility at ~1 MUA programming current by selecting a proper thickness
of Ti buffer layer. To achieve reliable BRS properties for low power application,
the operation current has been further optimized, whereas the memory device shows
pulse endurance of more than 7 million cycles at a low pulse width of 50 ns and
excellent data retention properties of more than 40 h at 150 degrees C
measurement temperature.
PMID- 28420241
TI - Percutaneous endoscopic gastrostomy in high risk ALS: insights to effort to
drawing a risk map.
PMID- 28420243
TI - Quantifying Medical Student Education and Exposure to Otolaryngology.
AB - OBJECTIVES: Evaluate the educational and exposure opportunities provided to
students by national otolaryngology organizations. METHODS: Twenty-four
otolaryngology organizations and subspecialty societies were reviewed for medical
student involvement opportunities, educational and enrichment opportunities,
costs of involvement, and available research and travel scholarships. RESULTS:
Nine organizations (37.5%) offered membership; 6 charged a membership fee,
averaging $73 +/- $30 (mean +/- SD). Membership was limited to associate status
for 7 organizations (77.8%; 7/9). Three organizations (12.5%) provided service
opportunities, 4 (16.7%) allowed students to vote, and 1 (4.2%) allowed students
to endorse others for membership. Most organizations allowed students to attend
conferences (95.8%), and 19 (79.2%) allowed students to present research. Twenty
one (87.5%) organizations charged a conference registration fee ($366 +/- $300).
Seven organizations (29.2%) offered research scholarships, and 5 (20.8%) offered
travel awards. CONCLUSIONS: Opportunities exist for medical students to attend
conferences and present research; however, educational and enrichment activities
in other areas were limited. Future efforts may be warranted to increase the
number and type of opportunities for students.
PMID- 28420242
TI - High prevalence of NDM metallo-beta-lactamase among ESBL-producing Escherichia
coli Isolates.
AB - Resistance to beta-lactams in Enterobacteriaceae has been increasing worldwide.
This study aimed to determine the frequency of beta-lactamase genes and
antibiotic resistance rates of 140 extended-spectrum beta-lactamase (ESBL)
producing Escherichia coli isolates obtained from urinary tract infection in Ordu
Province, Turkey. Isolates were identified by classic methods and by automated
system. ESBL production was confirmed by double disk synergy test and
antimicrobial susceptibility was investigated by disk diffusion method. All
isolates were screened for beta-lactamase coding genes from three groups (A, B,
and D) by polymerase chain reaction. The highest rate of susceptible isolates was
observed for imipenem (IPM, 99.3%) and ertapenem (ETP, 97.9%), and the highest
rate of resistant isolates was observed for cefuroxime (97.9%), ceftriaxone
(97.2%), and cefazolin (90.7%). In our study, blaCTX-M1-like group was the most
prevalent beta-lactamase (n = 109), followed by blaTEM (n = 68), blaCTX-M2 (n =
22), and blaSHV (n = 2). By contrast to low resistance rate to IPM and ETP, we
determined blaNDM in 31 isolates (22.1%). In co-prevalence of blaNDM-1 and ESBL
coding genes, a low carbapenem resistance was determined. We can confirm that
blaCTX-M1-types are still the most frequent beta-lactamase coding gene in Turkey.
Our study showed the highest prevalence of blaNDM-1 metallo-beta-lactamase coding
gene in ESBL-producing E. coli.
PMID- 28420244
TI - Occupation-based practices and homelessness: A scoping review.
AB - BACKGROUND: Persons experiencing or at risk of homelessness have occupational
needs that are seldom addressed in the Canadian system of care. The lack of
documented evidence on occupational therapy practices in this field hinders the
development of the profession. PURPOSE: This article identifies current and
potential practices that aim to enable or support the occupations of persons
experiencing or at risk of homelessness. METHOD: A scoping review was conducted,
including evidence from both occupational therapy and non-occupational therapy
sources. FINDINGS: One hundred and seventy-eight papers were selected in the
areas of occupational performance skills training, enrichment of occupational
repertoire, employment/education, physical rehabilitation services, child/family
services, community building, occupational transition from homeless to housed,
literacy, and disaster relief. IMPLICATIONS: Occupational therapists can build
environments and create opportunities that facilitate occupational engagement of
individuals experiencing homelessness. Gaps in knowledge include the evaluation
of occupational therapy practices, the Canadian context of family homelessness,
and the cultural safety of occupational therapy interventions.
PMID- 28420245
TI - A first approach to a neuropsychological screening tool using eye-tracking for
bedside cognitive testing based on the Edinburgh Cognitive and Behavioural ALS
Screen.
AB - OBJECTIVE: Reliable assessment of cognitive functions is a challenging task in
amyotrophic lateral sclerosis (ALS) patients unable to speak and write. We
therefore present an eye-tracking based neuropsychological screening tool based
on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a standard
screening tool for cognitive deficits in ALS. METHODS: In total, 46 ALS patients
and 50 healthy controls matched for age, gender and education were tested with an
oculomotor based and a standard paper-and-pencil version of the ECAS. RESULTS:
Significant correlation between both versions was observed for ALS patients and
healthy controls in the ECAS total score and in all of its ALS-specific domains
(all r > 0.3; all p < 0.05). The eye-tracking version of the ECAS reliably
distinguished between ALS patients and healthy controls in the ECAS total score
(p < 0.05). Also, cognitively impaired and non-impaired patients could be
reliably distinguished with a specificity of 95%. CONCLUSION: This study provides
first evidence that the eye-tracking based ECAS version is a promising approach
for assessing cognitive deficits in ALS patients who are unable to speak or
write.
PMID- 28420246
TI - Husband's Reaction to His Wife's Sexual Rejection Is Predicted by the Time She
Spends With Her Male Friends but Not Her Male Coworkers.
AB - Males among many species, including humans, evaluate cues of sperm competition
risk and adjust accordingly their sperm competition tactics. The number of
potential sexual rivals can serve as an index of sperm competition risk.
Therefore, men may adjust their in-pair copulatory interest in accordance with
the presence of sexual rivals. Using self-reports from 45 married men, we test
the hypotheses that the time a man's wife spends with other men-either male
friends or male coworkers-will positively predict a man's copulatory interest in
his wife (Hypothesis 1) and his anger (Hypothesis 2), upset (Hypothesis 3), and
frustration (Hypothesis 4) in response to his wife's sexual rejection. The
results show that the time wives spend with male friends (but not male coworkers)
predicts their husbands' anger, upset, and frustration in response to sexual
rejection, providing support for Hypotheses 2-4. Discussion highlights novel
contributions of the current research and provides a potential explanation for
the discrepant findings regarding male friends versus male coworkers.
PMID- 28420247
TI - Clinical and radiological outcomes after decompression and posterior fusion in
patients with degenerative scoliosis.
AB - OBJECTIVE: The prevalence of degenerative scoliosis (DS) increases with age and
an overall increase is seen due to the aging population. This study aims to
evaluate the clinical and radiological outcomes after decompression and posterior
fusion in patients with DS. METHODS: In this is prospective study, 43 patients
with DS, aged 37 to 70 years, were eligible to undergo decompression and
posterior fusion. Primary outcomes were low back pain (LBP) with or without
radicular pain, which was evaluated preoperatively and at 12 and 24 months after
surgery with the use of a visual analog scale (VAS), and the quality of life
(QOL), which was assessed at the same time periods by the Oswestry Disability
Index (ODI) questionnaire. The Cobb's method was used to measure the degree of
scoliosis in each patient preoperatively and at 24 hours, 12 and 24 months after
the surgery. RESULTS: VAS scores improved significantly from a mean of 8.18
preoperatively to 4.48 at 12 months and 3.07 at 24 months postoperatively (P <
.001). The mean radicular pain scores also decreased significantly (P < .001). At
postoperative 12 months, the mean ODI score was significantly lower than the mean
preoperative ODI score (47.81 +/- 16.06 vs. 72.18 +/- 12.28; P = .001). ODI score
at 24 months postoperatively was significantly better than the preoperative ODI
(15.53 +/- 7.21 vs. 72.18 +/- 12.28; P = .016). The mean Cobb angle changed
significantly from 31.4 degrees +/- 4.88 preoperatively to 3.28 degrees +/-
2.10 at 24 months postoperatively (P < .001). CONCLUSIONS: Our findings suggest
that decompression and posterior fusion in the patients with DS is an effective
surgical method which is associated with satisfying clinical results in terms of
improvement of postoperative LBP, radicular pain, and QOL, and correction of Cobb
angle at 12 and 24 months after the surgery and restoration of sagittal alignment
at 2 months postoperatively.
PMID- 28420248
TI - Creating an Optimal 3D Printed Model for Temporal Bone Dissection Training.
AB - OBJECTIVE: Making a 3-dimensional (3D) temporal bone model is simple using a
plaster powder bed and an inkjet printer. However, it is difficult to reproduce
air-containing spaces and precise middle ear structures. The objective of this
study was to overcome these problems and create a temporal bone model that would
be useful both as a training tool and for preoperative simulation. METHODS:
Drainage holes were made to remove excess materials from air-containing spaces,
ossicle ligaments were manually changed to bony structures, and small and/or soft
tissue structures were colored differently while designing the 3D models. The
outcomes were evaluated by 3 procedures: macroscopic and endoscopic inspection of
the model, comparison of computed tomography (CT) images of the model to the
original CT, and assessment of tactile sensation and reproducibility by 20
surgeons performing surgery on the model. RESULTS: Macroscopic and endoscopic
inspection, CT images, and assessment by surgeons were in agreement in terms of
reproducibility of model structures. Most structures could be reproduced, but the
stapes, tympanic sinus, and mastoid air cells were unsatisfactory. Perioperative
tactile sensation of the model was excellent. CONCLUSIONS: Although this model
still does not embody perfect reproducibility, it proved sufficiently practical
for use in surgical training.
PMID- 28420249
TI - Increasing HIV testing among pregnant women in Nigeria: evaluating the
traditional birth attendant and primary health center integration (TAP-In) model.
AB - Engaging Traditional Birth Attendants (TBAs) may be critical to preventing mother
to-child transmission of HIV (PMTCT) in Nigeria. We integrated TBAs into Primary
Health Centers (PHCs) and provided the TBAs with HIV counseling and testing (HCT)
training for PMTCT (TAP-In). The purpose of this study was to evaluate the impact
of TAP-In on HCT uptake among pregnant women. A quasi-experimental design was
used for this study. Twenty PHCs were assigned to the intervention group that
integrated TAP-In and 20 were assigned to the control group. Data were collected
six months prior to the initiation of TAP-In and six months post, using antenatal
clinic registries. Intervention PHCs more than doubled the number of pregnant
women who received HCT in their catchment area post TAP-In while control PHCs had
no significant change. After initiating TAP-In, intervention PHCs provided almost
three times more HCT than the control PHCs (p < 0.01) with TBA provided over half
of the HCT post TAP-In. The TAP-In model was effective for increasing HCT among
pregnant women.
PMID- 28420251
TI - Differential Diagnosis of Diaper Dermatitis.
AB - Mild diaper dermatitis often occurs in children before toilet training is
complete, particularly from 9 to 12 months of age, and the most common
presentation is an irritant contact dermatitis. Diaper dermatitis may account for
up to 25% of dermatology visits to health care providers during the first year of
life. Fortunately, since the introduction of hypoallergenic, superabsorbent
modern disposable diapers, the incidence and severity of irritant and allergic
contact dermatitis has decreased dramatically. Diaper dermatitis broadly refers
to skin disorders that occur in the diaper area, such as skin eruptions triggered
by diapers, rashes exacerbated by the diaper, and other events that occur in the
diaper area. A number of skin conditions that can occur anywhere on the skin may
present with distinctive findings in the diaper area. The following discussion
will review the most common triggers of diaper dermatitis and contact irritant
dermatitis, while focusing on the skin conditions that may be associated or
overlap clinically with contact dermatitis.
PMID- 28420252
TI - Diaper Dermatitis: Facts and Misinformation.
PMID- 28420250
TI - The European Association of Preventive Cardiology Exercise Prescription in
Everyday Practice and Rehabilitative Training (EXPERT) tool: A digital training
and decision support system for optimized exercise prescription in cardiovascular
disease. Concept, definitions and construction methodology.
AB - Background Exercise rehabilitation is highly recommended by current guidelines on
prevention of cardiovascular disease, but its implementation is still poor. Many
clinicians experience difficulties in prescribing exercise in the presence of
different concomitant cardiovascular diseases and risk factors within the same
patient. It was aimed to develop a digital training and decision support system
for exercise prescription in cardiovascular disease patients in clinical
practice: the European Association of Preventive Cardiology Exercise Prescription
in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT
working group members were requested to define (a) diagnostic criteria for
specific cardiovascular diseases, cardiovascular disease risk factors, and other
chronic non-cardiovascular conditions, (b) primary goals of exercise
intervention, (c) disease-specific prescription of exercise training (intensity,
frequency, volume, type, session and programme duration), and (d) exercise
training safety advices. The impact of exercise tolerance, common cardiovascular
medications and adverse events during exercise testing were further taken into
account for optimized exercise prescription. Results Exercise training
recommendations and safety advices were formulated for 10 cardiovascular
diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes,
obesity, hypertension, hypercholesterolaemia), and three common chronic non
cardiovascular conditions (lung and renal failure and sarcopaenia), but also
accounted for baseline exercise tolerance, common cardiovascular medications and
occurrence of adverse events during exercise testing. An algorithm, supported by
an interactive tool, was constructed based on these data. This training and
decision support system automatically provides an exercise prescription according
to the variables provided. Conclusion This digital training and decision support
system may contribute in overcoming barriers in exercise implementation in common
cardiovascular diseases.
PMID- 28420253
TI - Myths on Chemical Burns in the Diaper Area.
AB - Over the past several years, a number of articles and online posts have
circulated on the Internet associating use of disposable and cloth diapers with
chemical burns on babies' skin. Because both mild chemical burns and diaper
dermatitis (diaper rash) can cause skin redness and peeling, it is not surprising
that some confusion has arisen regarding the association between these two
conditions. However, diapers cannot cause chemical burns because they are made of
inert materials. Diaper rash and chemical burns are distinct conditions that
require different evaluation and treatment, which is why it is important for
pediatricians to help parents understand the difference.
PMID- 28420254
TI - Common Diaper Ingredient Questions: Modern Disposable Diaper Materials Are Safe
and Extensively Tested.
AB - Today's disposable diapers are high-performance and well-tested products,
designed to keep skin dry and healthy. They are primarily made of biologically
inert polymers, commonly used in fabrics and other materials that are in contact
with skin, and in foods and cosmetics. Still, product safety and ingredients in
everyday products can be a source of anxiety for new parents. This article
provides the facts behind some commonly asked questions from consumers about
diaper ingredients and safety, including myths and facts related to chlorine,
latex, dyes, and chemical additives.
PMID- 28420255
TI - Chemical and Common Burns in Children.
AB - Burns are a common cause of preventable morbidity and mortality in children.
Thermal and chemical burns are the most common types of burns. Their clinical
appearance can be similar and the treatment is largely similar. Thermal burns in
children occur primarily after exposure to a hot surface or liquid, or contact
with fire. Burns are typically classified based on the depth and total body
surface area, and the severity and onset of the burn can also depend on the
temperature and duration of contact. Chemical burns are caused by chemicals-most
commonly acids and alkalis-that can damage the skin on contact. In children, the
most common cause of chemical burns is from household products such as toilet
bowl cleaners, drain cleaners, detergents, and bleaches. Mild chemical burns
generally cause redness and pain and can look similar to other common rashes or
skin infections, whereas severe chemical burns are more extreme and may cause
redness, blistering, skin peeling, and swelling.
PMID- 28420256
TI - Accuracy of a Pediatric Behavioral Health Screener to Detect Untreated Behavioral
Health Problems in Primary Care Settings.
AB - An estimated 10% to 20% of youth in primary care exhibit behavioral symptoms and
may go underdetected. Most screeners identify risk base of symptoms alone,
irrespective of functional impairment. To address this issue, the Pediatric
Symptom Checklist-17 (PSC-17), a widely used symptom screener, was combined with
functional impairment and current behavioral services enrollment items to form
the Pediatric Behavioral Health Screen (PBHS) and assessed compared to the full
Child Behavior Checklist (CBCL). A total of 267 youth between 6 and 16 years of
age were administered the screener and the CBCL. Areas under the receiver
operating curves approached or exceeded 0.90 in all analyses, reflecting
excellent classification accuracy. Almost no false negatives were observed among
currently untreated cases with functional impairment. No differential item
functioning was found. Performance of the PSC-17 as a pediatric primary care
behavioral health screener supported previous research, and additional functional
impairment items to form the PBHS appeared useful, particularly for interpreting
borderline range scores.
PMID- 28420257
TI - Gestational Diabetes Management Using Smart Mobile Telemedicine.
AB - Gestational diabetes (GDM) burden has been increasing progressively over the past
years. Knowing that intrauterine exposure to maternal diabetes confers high risk
for macrosomia as well as for future type 2 diabetes and obesity of the
offspring, health care organizations try to provide effective control in spite of
the limited resources. Artificial-intelligence-augmented telemedicine has been
proposed as a helpful tool to facilitate an efficient widespread medical
assistance to GDM. The aim of the study we present was to test the feasibility
and acceptance of a mobile decision-support system for GDM, developed in the
seventh framework program MobiGuide Project, which includes computer
interpretable clinical practice guidelines, access to data from the electronic
health record as well as from glucose, blood pressure, and activity sensors. The
results of this pilot study with 20 patients showed that the system is feasible.
Compliance of patients with blood glucose monitoring was higher than that
observed in a historical group of 247 patients, similar in clinical
characteristics, who had been followed up for the 3 years prior to the pilot
study. A questionnaire on the use of the telemedicine system showed a high degree
of acceptance.
PMID- 28420258
TI - Lace Up for Healthy Feet: The Impact of Shoe Closure on Plantar Stress Response.
AB - OBJECTIVE: This study examined the impact of shoe closure on plantar thermal
stress response (TSR), which is known to be a surrogate of shear stress and skin
perfusion. It is aimed to explore potential impact of shoe closure on increasing
risk factors associated with plantar ulcers in people with diabetic peripheral
neuropathy (DPN). METHODS: Fifteen eligible subjects were enrolled. The left foot
was used as a reference and fitted to a self-adjusted and habitual lace
tightening method by each subject. The right foot was used as a test closure and
fitted into three lace closure conditions: loose, tight, and preset optimal
closure (reel clutch, BOA technology). Thermal images were taken after 5 minutes
of acclimatization (pre-trial) and immediately after 200 walking steps in each
shoe closure condition (post-trial). TSR was calculated from the thermal images.
RESULTS: TSR was significantly higher in the test closure with loose (70.24%, P =
.000) and tight (66.85%, P = .007) and lower (-206.53%, P = .000) in the preset
optimal closure when compared to the reference closure. Only lace closure
conditions affected TSR with no significant impact from age, BMI, and gender in
our sample in a multivariable regression model. CONCLUSION: The results from this
study suggest that shoelace closure technique can have a profound effect on TSR.
It therefore stands to reason that optimal lace closure may have an impact in
reducing risk of plantar ulcers in people with DPN. Interestingly, results
revealed that even a self-adjusted lace closure may not be necessarily optimal
and a preset closure setting like reel clutch might ultimately be recommended to
minimize risk. Further study is warranted to confirm or refute these interesting
results.
PMID- 28420259
TI - Seasonality of Insulin Use in German Outpatients With Diabetes: A Retrospective
Analysis.
AB - BACKGROUND: Seasonality in insulin sensitivity has been the focus of
controversial literature in the past decades. The aim of this study was to
analyze seasonality of insulin use in patients with diabetes who were followed in
German general practices. METHODS: This study included patients affected by type
1 (T1DM) or type 2 diabetes mellitus (T2DM) who received intensified conventional
insulin therapy over a period of at least 12 months between 2013 and 2015. The
main outcome was the median insulin dose per day (calculated daily insulin doses,
CDDs) between June and August (summer) and between December and February
(winter). RESULTS: The present study included 1197 T1DM patients and 3836 T2DM
patients from 492 general practitioner or diabetologist practices. The mean age
was 45.4 years (SD = 16.2 years) in the T1DM group and 65.2 years (SD = 14.1
years) in the T2DM group. The most frequent basal insulin therapy was insulin
glargine (T1DM: 45.7%; T2DM: 41.1%), and the most frequent bolus insulin therapy
was insulin lispro in the T1DM group (38.7%) and human insulin in the T2DM group
(45.2%). The consumption of basal and bolus insulins did not significantly differ
between summer and winter in T1DM individuals (basal therapy: 30.8 international
units (IU)/day versus 31.2 IU/day; bolus therapy: 39.4 IU/day versus 37.8
IU/day). This consumption was also similar between the two seasons in the T2DM
group (basal therapy: 31.0 IU/day versus 30.6 IU/day; bolus therapy: 44.3 IU/day
versus 44.1 IU/day). CONCLUSIONS: There was no significant difference in the use
of basal and bolus insulin therapies between summer and winter in German patients
with T1DM or T2DM.
PMID- 28420260
TI - The Safety of Nonadjunctive Use of Continuous Glucose Monitors for Insulin
Dosing: Still Not Resolved.
PMID- 28420261
TI - Added Value of Early Literacy Screening in Preschool Children.
AB - The Early Literacy Screener (ELS) is a brief screen for emergent literacy delays
in 4- and 5-year-olds. Standard developmental screens may also flag these
children. What is the value of adding the ELS? Parents of children aged 4 (n =
45) and 5 (n = 26) years completed the Ages and Stages Questionnaire-3 (ASQ-3),
the Survey of Well-Being in Young Children (SWYC), and the ELS. Rates of positive
agreement (PA), negative agreement (NA), and overall agreement (Cohen's kappa)
across the various screening tools were calculated. Early literacy delays were
detected in 51% of those who passed the ASQ and 38% of those who passed the SWYC.
For ELS versus ASQ, kappa = 0.18, PA = 0.36 (95% CI = 0.23-0.51), and NA = 0.83
(95% CI = 0.66-0.92). For ELS versus SWYC, kappa = 0.42, PA = 0.61 (95% CI = 0.45
0.75), and NA = 0.82 (95% CI = 0.65-0.92). The ELS adds value by flagging early
literacy delays in many children who pass either the ASQ-3 or SWYC.
PMID- 28420262
TI - Impact of an Educational Intervention to Improve Physician Adherence to
Bronchiolitis Clinical Practice Guidelines: A Pre-Post Intervention Study.
AB - Bronchiolitis is the leading cause of infant hospitalizations in the United
States. Despite clinical practice guidelines discouraging the utilization of non
evidence-based therapies, there continues to be wide variation in care and
resource utilization. A pre-post physician focused educational intervention was
conducted with the aims to reduce the use of non-evidence-based medical
therapies, including bronchodilators, among patients admitted for bronchiolitis.
Among patients meeting inclusion criteria (pre: n = 45; post: n = 47),
bronchodilator use decreased by 50% ( P < .001). Antibiotic use increased by 9% (
P < .02), although results remained within published acceptable utilization rates
of less than 19%. There were no statistical differences in chest X-ray,
respiratory viral panel, and steroid use. There were no differences in number of
pediatric intensive care unit transfers, 30-day readmission rates, and mean
length of stay. The findings demonstrate that a physician-focused educational
intervention highlighting American Academy of Pediatrics clinical practice
guidelines resulted in reduced utilization of bronchodilators.
PMID- 28420263
TI - An Unusual Cause of Frequent, Sudden, Transient, Unexplained Falls and New-Onset
Status Epilepticus: Case Report and Mini-Review.
AB - We report a 14-year old adolescent Caucasian female, who presented with frequent,
sudden, transient, and unexplained falls leading to multiple serious injuries to
her head and extremities requiring several visits to the emergency department.
She was evaluated numerous times and imaging studies, echocardiogram,
electrocardiogram, and electroencephalogram studies were all normal. She
eventually presented to outside emergency department with dystonic posturing and
status epilepticus and was transferred to our pediatric intensive care unit for
further management. She was diagnosed with an uncommon, underrecognized and
underdiagnosed condition. To our knowledge there is no such previous report in a
pediatric patient.
PMID- 28420264
TI - The Rate of Sepsis in a National Pediatric Population, 2006 to 2012.
AB - INTRODUCTION: The rate of pediatric severe sepsis is reported to be on the rise
in the United States, increasing by approximately 6000 cases annually. The goal
of this study was to determine the rate of pediatric sepsis per 100 000 inpatient
discharges over time. METHODS: The 2006, 2009, and 2012 Agency for Healthcare
Research and Quality Healthcare Cost Utilization Project Kid's Inpatient
Databases were used to analyze the rate of sepsis in children over time. RESULTS:
The rate of pediatric sepsis has increased over time from 92.8 per 100 000 in
2006 to 158.7 per 100 000 in 2012. Children less than a year old with Medicaid
coverage and 3 or more procedures during hospitalization have significantly
higher rates than their counterparts. CONCLUSIONS: This study helps clarify the
population demographics that are at greater risk for sepsis infections.
Understanding the at-risk population aids policymakers and care providers in
targeting these populations and make drastic changes to sepsis policies.
PMID- 28420265
TI - iCHAMPSS: Usability and Psychosocial Impact for Increasing Implementation of
Sexual Health Education.
AB - INTRODUCTION: Diffusion of sexual health evidence-based programs (EBPs) in
schools is a complex and challenging process. iCHAMPSS ( CHoosing And Maintaining
effective Programs for Sex education in Schools) is an innovative theory- and Web
based decision support system that may help facilitate this process. The purpose
of this study was to pilot-test iCHAMPSS for usability and short-term
psychosocial impact. METHOD: School district stakeholders from across Texas were
recruited ( N = 16) and given access to iCHAMPSS for 3 weeks in fall 2014. Pre-
and posttests were administered to measure usability parameters and short-term
psychosocial outcomes. Data were analyzed using descriptive statistics and the
Wilcoxon signed-rank test. RESULTS: Most participants reported that iCHAMPSS was
easy to use, credible, helpful, and of sufficient motivational appeal. iCHAMPSS
significantly increased participants' self-efficacy to obtain approval from their
board of trustees to implement a sexual health EBP. Positive, though
nonsignificant, trends included increased knowledge to locate EBPs, skills to
prioritize sexual health education at the district level, and ability to choose
an EBP that best meets district needs. CONCLUSIONS: iCHAMPSS is an innovative
decision support system that could accelerate uptake of EBPs by facilitating
diffusion and advance the field of dissemination and implementation science for
the promotion of sexual health EBPs.
PMID- 28420266
TI - Lessons Learned From the Field-Testing of Healthy Love: An HIV Prevention
Intervention for Black Women.
AB - BACKGROUND: Healthy Love is a brief, highly interactive, single-session, group
level HIV prevention intervention designed for African American women that is
effective at reducing sex risk behaviors and increasing condom use and HIV
testing among participants. The Centers for Disease Control and Prevention,
through a contract, developed a user-friendly intervention package that would
allow organizations to adopt and implement Healthy Love with fidelity. METHOD:
Training and implementation materials were developed to support original research
protocols, and piloted and revised to conduct field-testing with case study
agencies (CSAs). Three CSAs were selected to deliver the intervention over a 3
month period to test the utility of intervention materials and feasibility of
implementation. RESULTS: All CSAs were able to successfully deliver 10 sessions
with a total of 185 women ranging from 18 to 59 years of age. Successes and
challenges encountered in training, preimplementation activities, and
intervention delivery are described. DISCUSSION: Lessons learned from training,
technical assistance, and process monitoring and evaluation informed final
package revisions. Research to practice recommendations are shared as is guidance
for future implementations of Healthy Love. The research to practice process used
is a model approach for developing a comprehensive intervention package and will
support the adoption of Healthy Love by other organizations.
PMID- 28420267
TI - Promoting Health Through Policy and Systems Change: Public Health Students and
Mentors on the Value of Policy Advocacy Experience in Academic Internships.
AB - Emerging professionals and new Certified Health Education Specialists often lack
academic training in and actual experience in National Commission for Health
Education Credentialing Area of Responsibility VII: Communicate, Promote, and
Advocate for Health, Health Education/Promotion, and the Profession. For
undergraduate and graduate students who have an opportunity to complete an
internship or practicum experience, gaining experience in Competencies 7.2:
Engage in advocacy for health and health education/promotion and 7.3: Influence
policy and/or systems change to promote health and health education can have a
profound impact on their career development and their ability to advocate for
policies that promote health and health equity. Compelling evidence suggests that
interventions that address social determinants of health such as poverty and
education and those that change the context through improved policy or healthier
environments have the greatest impact on public health, making it vital for
emerging public health professionals to gain experience in policy advocacy and
systems change. In this commentary, students and faculty from two large
universities in the U.S.-Mexico border region reflect on the value of policy
advocacy in academic internship/fieldwork experiences. Based on their
experiences, they highly recommend that students seek out internship
opportunities where they can participate in policy advocacy, and they encourage
university faculty and practicum preceptors to provide more opportunities for
policy advocacy in both classroom and fieldwork settings.
PMID- 28420269
TI - Strengthening Social Ties to Increase Confidence and Self-Esteem Among Sexual and
Gender Minority Youth.
AB - Sexual and gender minority (SGM) youth too often live in nonsupportive
environments. This study reports the influence of social support from primary and
secondary social ties on confidence and self-esteem among participants in Hatch
Youth, a drop-in group-level intervention for SGM youth. Each 3-hour Hatch Youth
meeting consists of a social, educational, and youth-led support hour. Over 14
weeks, these meetings were randomly observed and individual interviews with
participating youth ( n = 12) and staff and volunteers ( n = 12) were conducted;
data underwent a content analysis. Participants perceived an increase in
confidence and self-esteem through enhanced bonding with family and friends, a
sense of belonging, and community empowerment because of their involvement with
Hatch Youth, suggesting drop-in centers can strengthen secondary social ties and
improve confidence and self-esteem.
PMID- 28420270
TI - Stages of change in audiology: comparison of three self-assessment measures.
AB - OBJECTIVE: In a clinical setting, theories of health behaviour change could help
audiologists and other hearing health care professionals understand the barriers
that prevent people with hearing problems to seek audiological help. The
transtheoretical (stages of change) model of health behaviour change is one of
these theories. It describes a person's journey towards health behaviour change
(e.g. seeking help or taking up rehabilitation) in separate stages:
precontemplation, contemplation, preparation, action, and, finally, maintenance.
A short self-assessment measure of stages of change may guide the clinician and
facilitate first appointments. This article describes correlations between three
stages of change measures of different lengths, one 24-item and two one-item.
DESIGN: Participants were recruited through an online hearing screening study.
Adults who failed the speech-in-noise recognition screening test and who had
never undergone a hearing aid fitting were invited to complete further
questionnaires online, including the three stages of change measures. STUDY
SAMPLE: In total, 224 adults completed the three measures. RESULTS: A majority of
the participants were categorised as being in one of the information- and help
seeking stage of change (contemplation or preparation). The three stages of
change measures were significantly correlated. Conclusions Our results support
further investigating the use of a one-item measure to determine stages of change
in people with hearing impairment.
PMID- 28420271
TI - Imaging TMS: antidepressant mechanisms and treatment optimization.
AB - With the antidepressant efficacy of Transcranial Magnetic Stimulation well
established by several meta-analyses, there is growing interest in its mechanism
of action. TMS has been shown to engage, and in some cases, normalize functional
connectivity and neurotransmitter levels within networks dysfunctional in the
depressed state. In this review, I will suggest candidate biomarkers, based on
neuroimaging, that may be predictive of response to TMS. I will then review the
effects of TMS on networks and neurotransmitter systems involved in depression.
Throughout, I will also discuss how our current understanding of response
predication and network engagement may be used to personalize treatment and
optimize its efficacy.
PMID- 28420273
TI - Role of inflammation in the association between the western dietary pattern and
metabolic syndrome among Lebanese adults.
AB - : The aim of this study was to investigate whether inflammation mediates the
previously observed direct association between the western dietary pattern (WDP)
and metabolic syndrome (MetS) among Lebanese adults. Sociodemographic, lifestyle,
dietary pattern scores, anthropometric and biochemical data of 331 adults were
used in this study. Inflammation indicators considered were: serum C-reactive
protein (CRP) and the dietary inflammatory index (DII). The scores of the WDP
were significantly associated with DII (r = .64) but not with serum CRP. Higher
CRP levels increased the odds of MetS and four out of five of its components,
while no association was found between the DII and MetS. CONCLUSION: The findings
of this study confirmed the association of serum CRP with MetS but did not
support mediation effect of inflammation on the association between the WDP and
MetS. These findings are important to direct future investigations on diet,
inflammation and association with diseases risk.
PMID- 28420272
TI - Resveratrol suppresses hyperoxia-induced nucleocytoplasmic shuttling of SIRT1 and
ROS production in PBMC from preterm infants in vitro.
AB - OBJECTIVE: By assessing silent mating-type information regulation 2 homolog 1
(SIRT1) nucleocytoplasmic shuttling and reactive oxygen species (ROS) levels in
peripheral blood mononuclear cells (PBMCs), this study aimed to explore the role
of SIRT1 in premature infants after exposure to hyperoxia and assess the
protective effects of resveratrol (Res). METHODS: Firstly, ROS levels as well as
SIRT1 translocation and expression in PBMCs samples were evaluated from 40
premature infants with different oxygen amounts received at birth. Then, PBMCs,
from additional 40 premature infants administered no oxygen at birth, were used
to establish an in vitro model of hyperoxia. RESULTS: In infants that received O2
at birth, ROS and MDA levels, and SIRT1 translocation rates gradually increased
in a concentration-dependent manner, while SIRT1 gradually decreased. In
agreement, PBMCs cultured in vitro showed increased ROS levels after exposed to
hyperoxia, SIRT1 translocation increased as well. However, treatment with Res
resulted in opposite effects. CONCLUSION: Res inhibits ROS release in PBMCs from
preterm infants exposed to hyperoxia, likely by preventing SIRT1
nucleocytoplasmic shuttling and increasing SIRT1 expression.
PMID- 28420274
TI - Comparison of serum folate, 25-OH vitamin D, and calcium levels between pregnants
with and without fetal anomaly of neural tube origin.
AB - AIM: The aim of this study was to compare serum folate, vitamin B12, 25-OH
vitamin D, and calcium levels between pregnants with and without fetal anomaly of
neural tube origin. METHODS: One hundred seventy-eight pregnants were recruited
for this study. Pregnants with and without sonographically detected fetal anomaly
of neural tube origin were compared in terms of serum folate, vitamin B12, 25-OH
vitamin D, and calcium levels. RESULTS: There were significant differences
between groups with regard to age, serum 25 OH vitamin D, 1,25 OH vitamin D,
folate, calcium, and B 12 levels. Multivariate regression analyses revealed
significant associations between the serum 25 OH vitamin D level, age, and the
neural tube defect (NTD). CONCLUSIONS: Vitamin D and the age of pregnants were
significantly associated with the NTDs.
PMID- 28420275
TI - Beta Hebbian Learning as a New Method for Exploratory Projection Pursuit.
AB - In this research, a novel family of learning rules called Beta Hebbian Learning
(BHL) is thoroughly investigated to extract information from high-dimensional
datasets by projecting the data onto low-dimensional (typically two dimensional)
subspaces, improving the existing exploratory methods by providing a clear
representation of data's internal structure. BHL applies a family of learning
rules derived from the Probability Density Function (PDF) of the residual based
on the beta distribution. This family of rules may be called Hebbian in that all
use a simple multiplication of the output of the neural network with some
function of the residuals after feedback. The derived learning rules can be
linked to an adaptive form of Exploratory Projection Pursuit and with artificial
distributions, the networks perform as the theory suggests they should: the use
of different learning rules derived from different PDFs allows the identification
of "interesting" dimensions (as far from the Gaussian distribution as possible)
in high-dimensional datasets. This novel algorithm, BHL, has been tested over
seven artificial datasets to study the behavior of BHL parameters, and was later
applied successfully over four real datasets, comparing its results, in terms of
performance, with other well-known Exploratory and projection models such as
Maximum Likelihood Hebbian Learning (MLHL), Locally-Linear Embedding (LLE),
Curvilinear Component Analysis (CCA), Isomap and Neural Principal Component
Analysis (Neural PCA).
PMID- 28420276
TI - The influence of maternal vaginal flora on the intestinal colonization in
newborns and 3-month-old infants.
AB - AIM: The role of maternal vaginal bacteria on the colonization of neonatal gut is
still a matter of discussion. Our aim was to estimate the role of maternal
vaginal flora on the development of intestinal flora in neonates and 3-month-old
infants. METHODS: Seventy-nine maternal-neonatal pairs were included in the
study. Vaginal swabs were taken before the rupture of membranes after admission
to the delivery ward. First neonatal stool (meconium) and stool at 3-month-old
infants were collected and cultured. All samples were subjected to
microbiological analysis for Streptococcus, Staphylococcus, Bifidobacterium,
Clostridium (including C. difficile), Lactobacillus, Escherichia coli, Klebsiella
pneumoniae, and Candida. RESULTS: Maternal vagina was colonized mainly by
streptococci (67%) followed by lactobacilli (58%) and Candida spp. (39%). Vaginal
streptococci influenced the intestinal colonization in infants with
staphylococci, C. difficile, and candida. CONCLUSION: Vaginal lactobacilli
influenced colonization with C. difficile, and Candida. Vaginal flora is a potent
factor influencing the development of bacterial flora in the neonatal and
infantile gut. The extension of the observation period until 3 months of life
allow to discover the potential changes in the intestinal flora of children.
PMID- 28420277
TI - Device optimised chirp stimulus for ABR measurements with an active middle ear
implant.
AB - OBJECTIVE: Active middle ear implants are widely used to treat adults and
children with sensorineural, conductive, or mixed hearing loss. Currently, there
is no adequate method to determine the performance of active middle ear implant
systems. DESIGN: The proposed method is based on measuring the auditory brainstem
response while stimulating the hearing system via the active middle ear implant
(Vibrant SoundbridgeTM, VSB; MEDEL, Austria). The acoustic stimulation was
achieved via an optimised chirp stimulus (CE-Chirp), implemented in the Eclipse
system (Interacoustics, Denmark). To compensate for the frequency-specific delays
in the VSB system, the underlying model function of the CE-Chirp was adjusted
accordingly (VSB-CE-Chirp). Study samples: The study includes 12 subjects having
mild to profound sensorineural, conductive or mixed hearing loss. RESULTS: The
use of an optimised VSB-CE-Chirp instead of the CE-Chirp increases significantly
the ABR wave V amplitudes (1.63 times) and so also increases their
identifiability (by 15.2%). On average, wave V could be identified at a 7.5 dB
lower stimulation level. CONCLUSION: The constructed VSB-CE-Chirp stimulus, after
it had been transmitted through the VSB system, follows well the shape of the
original CE-Chirp. Preliminary measurements in VSB patients demonstrated a
significantly improved ABR amplitude with the VSB-CE-Chirp.
PMID- 28420278
TI - Audiometric features in young adults with Turner syndrome.
AB - OBJECTIVE: Hearing loss (HL) is a known problem in adults with Turner syndrome
(TS). The aim of this study was to investigate audiometric features in young
adults with TS and the extent of hearing aid provision. DESIGN: Patients were
recruited from the Turner centre at Karolinska University Hospital. Analysis of
audiograms was made in relation to hearing aid use, a Swedish normal hearing
cohort and the need for hearing rehabilitation. STUDY SAMPLE: Sixty-four women
with TS aged 25-38 years at the time of their audiological testing. RESULTS:
Fifty-two percent had impaired hearing in at least one ear. Sensorineural hearing
loss (SNHL) was the most common type of HL, most often characterised by a high
frequency loss and/or a mid-frequency dip. Conductive HL was uncommon in young
adults with TS, even though 47 percent were otitis prone as children. Eight of 64
women had previously been fitted with hearing aids. CONCLUSIONS: There is
undoubtedly a need for hearing rehabilitation in young adults with TS. Questions
about hearing must be asked by all doctors treating women with TS to identify
those in need for hearing rehabilitation, even if they have an audiogram with a
normal pure tone average.
PMID- 28420279
TI - Responses of blood mononucleated cells and clinical outcome of non-celiac gluten
sensitive pediatric patients to various cereal sources: a pilot study.
AB - Non-celiac gluten sensitivity (NCGS) is a clinical entity recently documented by
the scientific community in pediatric patients. Nevertheless, its triggering
mechanisms remain largely unsettled. We studied 11 children with NCGS who were
diagnosed based on a clear-cut relationship between wheat consumption and
development of symptoms, after excluding celiac disease (CD) and wheat allergy,
matched with 18 children with active CD. Sixteen pediatric patients were also
enrolled as controls. Cultured peripheral blood mononucleated cells (PBMCs)
obtained from NCGS, CD and control patients were cultured in the presence of
wheat proteins extracted from ancient and modern cultivars. Results demonstrated
that wheat proteins induced an overactivation of the proinflammatory chemokine
CXCL10 in PBMC from NCGS pediatric patients and that this overexpression also
depended on the wheat cultivar from which proteins were extracted. Proteins from
modern wheat cultivar activated CXCL10 to a greater extent than those extracted
from ancient wheat genotypes.
PMID- 28420280
TI - Enteric-coated budesonide for the induction and maintenance of remission of
Crohn's disease in children.
AB - OBJECTIVE: These studies evaluated the safety and efficacy of enteric-coated
budesonide for the induction and maintenance of remission of mild-to-moderate
Crohn's disease (CD) in children. METHODS: The consecutive, multicenter, open
label, non-comparative studies enrolled patients aged 6-17 years. In the
induction study, patients with active CD of the ileum and/or ascending colon
received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance
study, patients in remission received budesonide 6 mg once daily for 12 weeks.
The primary objective was assessment of safety, including glucocorticosteroid
related side effects and serum cortisol levels. Efficacy was assessed using the
Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of
life (HRQoL) using the IMPACT-III questionnaire. RESULTS: In the induction study
(n = 108), most adverse events were related to CD, commonly abdominal pain;
possible glucocorticosteroid-related effects included acne and increased appetite
but without significant weight gain. Subnormal morning cortisol levels were
observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity
from baseline (mean +/- standard deviation, 9.1 +/- 8.5 vs. 19.1 +/- 10.1, p <
.001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p <
.001). In the maintenance study (n = 50), mean disease activity worsened (p =
.047) with HRQoL unchanged (p = .33). CONCLUSIONS: Budesonide treatment was
generally well tolerated, although the potential for adrenal suppression was
noted. Budesonide was effective for induction of remission in children with mild
to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers:
NCT01444092, NCT01453946).
PMID- 28420281
TI - Long-term follow-up of antithrombotic management patterns in patients with acute
coronary syndrome in Russia: an observational study (EPICOR-RUS study).
AB - OBJECTIVE: This study sought to describe the short- and long-term (up to 2 years)
antithrombotic management patterns in a real-life setting for patients
hospitalized for an acute coronary syndrome (ACS) event, and to document clinical
outcomes. RESEARCH DESIGN AND METHODS: EPICOR-RUS was a multicenter (34 centers),
prospective, observational, longitudinal cohort study conducted across Russia on
antithrombotic management in hospitalized (within 24 hours of symptom onset) ACS
patients with 2 year follow-up. CLINICAL TRIAL REGISTRATION: NCT01373957.
RESULTS: A total of 600 ACS patients (71.1% male, mean age 60 years) were
enrolled; 599 were included for analysis. Diagnosis comprised STEMI (n = 375,
62.6%), NSTEMI (n = 147, 24.5%), and unstable angina (UA) (n = 77, 12.9%).
Percutaneous coronary intervention (PCI) was conducted in 64.3% of patients with
STEMI (with or without thrombolysis), 36.7% with NSTEMI, and 58.4% with UA. There
was undertreatment with dual antiplatelet therapy (DAPT) for STEMI, NSTEMI, and
UA: 14.7%, 25.9% and 16.9% of patients, respectively, were not receiving DAPT
during hospitalization, and 10.1%, 21.8% and 16.9% at discharge. Post-discharge,
of the STEMI group, only 72.4% of patients who were managed by PCI and 39.8% of
conservatively treated patients received DAPT at 12 months. The respective
figures in the NSTEMI group were 77.3% and 26.4%. In the STEMI cohort the
cumulative incidence of all-cause mortality was 3.2% at 1 year and 5.1% at 2
years of follow-up; in the NSTEMI cohort this was 2.7% and 4.8%, respectively.
There were no deaths by 12 months and one death by 24 months (1.3%) in the UA
population. CONCLUSION: Despite evidence-based guidelines for the management of
ACS, the real-world setting in Russia shows discrepancies in clinical practice,
highlighting the need for improvements for the optimal management of high-risk
patients with ACS.
PMID- 28420282
TI - Exploring predictors of treatment outcome in cognitive behavior therapy for sleep
disturbance following acquired brain injury.
AB - PURPOSE: To identify predictors of treatment response to cognitive behavior
therapy (CBT) for sleep disturbance following acquired brain injury (ABI).
METHODS: Classification and regression tree (CART) analysis was conducted on
individual patient data from two pilot randomized controlled trials (RCTs): one
in traumatic brain injury (TBI), the other in stroke. The combined sample
comprised 32 participants; 15 receiving CBT and 17 allocated to treatment as
usual (TAU). The outcome was reliable improvement on the Pittsburgh Sleep Quality
Index (PSQI). RESULTS: Study group was a statistically significant predictor of
outcome, with CBT participants more likely to achieve reliable improvements than
TAU (OR = 4.88, p = 0.042). Study group (CBT vs. TAU) exhibited an area under the
ROC curve (AUROC) of 69%. In separate CART analyzes, verbal memory (CVLT-II
>45.5), age (<47.5) and baseline depression (HADS-D > 6) predicted positive
outcomes in CBT recipients. Each of these variables added a small (~5%) but not
statistically significant amount to AUROC over study group. CONCLUSIONS: In this
ABI sample, better memory, younger age, and higher baseline depression were
associated with positive treatment response to CBT although individually these
variables were not better than group alone in predicting outcomes. The present
findings generate hypotheses for further investigation in future studies.
Implications for rehabilitation Cognitive behavior therapy improves sleep quality
over treatment as usual in persons with acquired brain injury. Individuals who
are younger in age with better memory and co-morbid symptoms of depression are
more likely to respond to the treatment. These findings are based on a small
sample and can be considered hypothesis generating for future clinical studies.
PMID- 28420283
TI - Design and characteristics of gellan gum beads for modified release of meloxicam.
AB - The aim of the presented work was to design, formulate and evaluate the
properties of low-acyl gellan macro beads with the potential application as
carriers for oral delivery of meloxicam (MLX) in the prophylaxis of colorectal
cancer. The beads were obtained by means of ionotropic gelation technique.
Calcium chloride (1.0%, 9.0 * 10-2 M) was used as the cross-linking agent. Nine
different polymer, drug and surfactant (Tween(r)80) mixtures were used for
production of the beads. The quantitative compositions of the mixtures were
generated with the application of the Design of Experiments (DoE) modulus from
the STATISTICA Software. The prepared formulations revealed 7.2-27.0% of drug
loading and 29.2-50.7% drug encapsulation efficiency. It turned out that 0.5%
amount of gellan gum in the mixtures was not sufficient to obtain spherical
beads. The morphology and surface of the dried beads were analyzed by SEM. Raman
spectra confirmed that MLX did not undergo structural changes during production
of the beads. The swelling behavior and degradation of the beads were evaluated
in three simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8). The
MLX in vitro release studies were conducted on USP apparatus IV, working in the
open loop mode. The obtained results showed that MLX release from the dried beads
was pH-dependent. The formulations obtained from mixtures containing 1.0 and 1.5%
of gellan may be considered as oral dosage forms for MLX, intended to omit the
stomach and release the drug in the distal parts of the gastrointestinal tract.
PMID- 28420284
TI - A systematic review of rehabilitation interventions to prevent and treat
depression in post-stroke aphasia.
AB - PURPOSE: Stepped psychological care is the delivery of routine assessment and
interventions for psychological problems, including depression. The aim of this
systematic review was to analyze and synthesize the evidence of rehabilitation
interventions to prevent and treat depression in post-stroke aphasia and adapt
the best evidence within a stepped psychological care framework. METHOD: Four
databases were systematically searched up to March 2017: Medline, CINAHL,
PsycINFO and The Cochrane Library. RESULTS: Forty-five studies met inclusion and
exclusion criteria. Level of evidence, methodological quality and results were
assessed. People with aphasia with mild depression may benefit from psychosocial
type treatments (based on 3 level ii studies with small to medium effect sizes).
For those without depression, mood may be enhanced through participation in a
range of interventions (based on 4 level ii studies; 1 level iii-3 study and 6
level iv studies). It is not clear which interventions may prevent depression in
post-stroke aphasia. No evidence was found for the treatment of moderate to
severe depression in post-stroke aphasia. CONCLUSIONS: This study found some
interventions that may improve depression outcomes for those with mild depression
or without depression in post-stroke aphasia. Future research is needed to
address methodological limitations and evaluate and support the translation of
stepped psychological care across the continuum. Implications for Rehabilitation
Stepped psychological care after stroke is a framework with levels 1 to 4 which
can be used to prevent and treat depression for people with aphasia. A range of
rehabilitation interventions may be beneficial to mood at level 1 for people
without clinically significant depression (e.g., goal setting and achievement,
psychosocial support, communication partner training and narrative therapy).
People with mild symptoms of depression may benefit from interventions at level 2
(e.g., behavioral therapy, psychosocial support and problem solving). People with
moderate to severe symptoms of depression require specialist mental
health/behavioral services in collaboration with stroke care at levels 3 and 4 of
stepped psychological care.
PMID- 28420285
TI - Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a
mucolytic agent for cystic fibrosis patients.
AB - OBJECTIVE: This study aimed to design and characterize an inhalable dry powder of
ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and
dornase alfa for the management of pulmonary infections in patients with cystic
fibrosis. METHODS: Ball milling, homogenization in isopropyl alcohol and spray
drying processes were used to prepare dry powders for inhalation. Physico
chemical characteristics of the dry powders were assessed via thermogravimetric
analysis, differential scanning calorimetry (DSC), Fourier transform infrared
spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The
particle size distribution, dissolution rate and permeability across Calu-3 cell
monolayers were analyzed. The aerodynamic parameters of dry powders were
determined using the Andersen cascade impactor (ACI). RESULTS: After the
micronization process, the particle sizes of the raw materials significantly
decreased. X-ray and DSC results indicated that although ciprofloxacin showed no
changes in its crystal structure, the structure of levofloxacin became amorphous
after the micronization process. FT-IR spectra exhibited the characteristic peaks
for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of
micro-homogenized and spray-dried ciprofloxacin were higher than that of
untreated ciprofloxacin. ACI results showed that all formulations had a mass
median aerodynamic diameter less than 5 MUm; however, levofloxacin microparticles
showed higher respirability than ciprofloxacin powders did. The permeability of
levofloxacin was higher than those of the ciprofloxacin formulations. CONCLUSION:
Together, our study showed that these methods could suitably characterize
antibiotic and mucolytic-containing dry powder inhalers.
PMID- 28420286
TI - Probing the Characteristics of Colour-Motion Binding and Its Dependence on
Persistent Surface Segregation.
AB - Identifying the spatial and temporal characteristics of visual feature binding is
a remaining challenge in the science of perception. Within the feature-binding
literature, disparate findings have suggested the existence of more than one
feature-binding mechanism with differing temporal resolutions. For example, one
surprising result is that temporal alternations between two different feature
pairings of colour and motion (e.g., orange dots moving left with blue dots
moving right) support accurate conjunction discrimination at alternation
frequencies of around 10 Hz and greater. However, at lower alternation
frequencies around 5 Hz, conjunction discrimination falls to chance. To further
investigate this effect, we present two experiments that probe the stimulus
characteristics that facilitate or impede feature binding. Using novel
manipulations of random dot kinematograms, we identify that facilitating surface
representations through temporal integration can enable accurate conjunction
discrimination at both intermediate and high alternation frequencies. We also
offer a neurally plausible evidence accumulator model to describe these results,
removing the need to suggest multiple binding mechanisms acting at different
timescales. In effect, we propose a single, flexible binding process, whereby the
relatively low temporal resolution for binding features can be circumvented by
extracting them from rapidly formed and persistent surface representations.
PMID- 28420287
TI - Associations between early caregiving and rural, low-SES, African-American
children's representations of attachment relationships.
AB - Little research has examined the legacy of early maternal care for later
attachment representations among low-income and ethnic minority school-aged
children. Using data from a sample of 276 rural, low-income, African-American
families, this study examined associations between maternal care in infancy and
children's representations of attachment figures in middle childhood. Maternal
care was coded from 10-min home-based observations at 6, 15, and 24 months of
age. Representations of attachment figures were assessed using the Manchester
Child Attachment Story Task at 6 years of age. Sensitive maternal care in infancy
was not significantly related to attachment security or episodic disorganized
behaviors in children's representations. However, children exposed to more harsh
intrusive parenting during infancy displayed less secure representations of
attachment figures in middle childhood and more episodic disorganized behaviors,
even after controlling for numerous child and family contextual covariates.
Findings inform conceptualizations of attachment formation among rural, low
income, African-American parent-child dyads.
PMID- 28420288
TI - Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the
antifungal sertaconazole: design, optimization and ex vivo evaluation.
AB - The purpose of the present study was to develop and optimize sertaconazole
microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin
retention of the drug. Following screening of various oils for maximum drug
solubility, 12 pseudoternary phase diagrams were constructed using oils
(Peceol(r), Capryol(r) 90), surfactants (Tween(r) 80, Cremophor(r) EL), a
cosurfactant (Transcutol(r) P) and water. A 21 * 31 * 21 * 31 full factorial
design was employed to optimize a ME of desirable characteristics. The MEs were
formulated by varying the oil type, oil concentration, surfactant type and
surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol(r), 55%
Tween(r) 80: Transcutol(r) (1:2), 40% water] and F31 [5% Peceol(r), 55%
Cremophor(r) EL: Transcutol(r) (1:2), 40% water] acquired mean droplet size of
75.21 and 8.68 nm, and zeta potential of 34.65 and 24.05 mV, respectively. Since
F22 showed higher STZ skin retention during ex vivo studies (686.47 MUg/cm2) than
F31 (338.11 MUg/cm2); hence it was incorporated in 0.5% Carbopol 934 gel to
augment STZ skin retention capability. STZ ME G exhibited higher STZ skin
retention (1086.1 MUg/cm2) than the marketed product "Dermofix(r) cream" (270.3
MUg/cm2). The antimycotic activity against C.albicans revealed increased zones of
inhibition for F22 and STZ ME G (35.75 and 30.5 mm, respectively) compared to
Dermofix(r) cream (26 mm). No histopathological changes were observed following
topical application of STZ ME G on rats' skin (n = 9). Overall, the obtained
results confirmed that the fabricated formulation could be a promising vehicle
for the dermal delivery of STZ.
PMID- 28420289
TI - Rhinoscleroma: a chronic infectious disease of poor areas with characteristic
histological features - report of a series of six cases.
AB - Rhinoscleroma is a chronic infectious disease that is endemic in certain poor
areas of the world. The diagnosis often relies on pathology, the outcome is
disappointing and then marked by recurrence. We present a retrospective series of
six patients histologically diagnosed with rhinoscleroma. Some clinical and
histological features of the disease are discussed below, as its adequate
management implies a multidisciplinary approach.
PMID- 28420290
TI - Peripheral blood smear: beyond routine morphology.
PMID- 28420291
TI - A study of long-term stability and antimicrobial activity of chlorhexidine,
polyhexamethylene biguanide, and silver nanoparticle incorporated in sericin
based wound dressing.
AB - In this study, three kinds of antiseptics which were 0.05% chlorhexidine, 0.2%
polyhexamethylene biguanide (PHMB), or 200 ppm silver nanoparticle was introduced
to incorporate in the sericin-based scaffold to produce the antimicrobial
dressing for the treatment of infected chronic wound. The effects of antiseptic
incorporation on the stability, release of sericin, and short-term and long-term
(6 months) antimicrobial activity of the sericin dressing against gram-negative
and gram-positive bacteria were investigated. We showed that the incorporation of
each antiseptic did not have significant effect on the internal morphology (pore
size ~ 73-105 MUm), elasticity (Young's modulus ~ 200-500 kPa), and the sericin
release behavior of the sericin-based dressing. The release of sericin from the
dressing was prolonged over 120 h and thereafter. Comparing among three
antiseptics, 0.05% chlorhexidine incorporated in the sericin dressing showed the
highest immediate and long-term (6 months) antimicrobial effect (largest
inhibition zone) against most bacteria either gram-positive or gram-negative
bacteria. The in vivo safety test following ISO10993 standard (Biological
evaluation of medical devices - Part 6: Tests for local effects after
implantation) confirmed that the sericin dressing incorporating 0.05%
chlorhexidine did not irritate to tissue, comparing with the commercial material
used generally in clinic (Allevyn(r), Smith & Nephew). We suggested the sericin
dressing incorporating 0.05% chlorhexidine for the treatment of infected chronic
wound. Chlorhexidine would reduce the risk of infection while the sericin may
promote wound healing.
PMID- 28420292
TI - Neuroendocrine tumor of cecum in patient treated with imatinib mesylate for
blastic phase of chronic myeloid leukemia.
AB - Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice
in patients with chronic myeloid leukemia (CML). It is considered a very safe
drug, with mostly mild and reversible side effects. Lately, it has been suggested
that adverse events may occur after a long term. We report a case of a 72-year
old woman diagnosed with blastic phase of Philadelphia chromosome positive CML
treated with IM for 28 months. The patient presented first with ascites as a side
effect of the drug. When the ascites re-occurred, it was caused by neuroendocrine
tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of
a NET as a secondary malignancy (SM) after IM treatment. SM have been described
in patients on IM before. It is unclear whether these tumors are caused by
imatinib or found more easily because of close follow-up.
PMID- 28420293
TI - Acute gastric outlet obstruction secondary to exclusive paraoesophageal small
bowel herniation: a case report.
AB - INTRODUCTION: Herniation of abdominal viscera into the thorax may occur as a
consequence of abnormal defects in the diaphragm. In adults, the most common
condition relates to herniations through a weakened crural orifice via which the
oesophagus normally traverses. These hiatus hernias are classified as types I-IV
depending on the extent of visceral involvement. CASE REPORT: We present here a
case of type IV hiatus hernia with massive mediastinal herniation of the small
bowel, yet remarkable in that the stomach itself remained completely intra
abdominal. Gastric outlet obstruction occurred as a consequence of extrinsic
proximal small bowel compression. DISCUSSION: To our knowledge this is the first
reported case of paraoesophageal hernia exclusively involving small bowel,
without involving any part of the stomach, and yet causing gastric outlet
obstruction.
PMID- 28420294
TI - SMART - Recognising the value of existing practice and introducing recent
developments: leaving no stone unturned in the assessment and treatment of the
PDOC patient.
AB - Over the last 25 years there have been a number of papers highlighting the issues
of high rates of misdiagnosis in prolonged disorders of consciousness (PDOC)
(Andrews, K., Murphy, L., Munday, R., & Littlewood, C. (1996). Misdiagnosis of
the vegetative state: Retrospective study in a rehabilitation unit. BMJ,
313(7048), 13-16; Childs, N. L., Mercer, W. N., & Childs, H. W. (1993). Accuracy
of diagnosis of persistent vegetative state. Neurology, 43(8), 1465-1467).
Surprisingly, these rates still remain at the same level despite defined criteria
for diagnosis (Schnakers, C., Vanhaudenhuyse, A., Giacino, J., Ventura, M., Boly,
M., Majerus, S.,...Laureys, S. (2009). Diagnostic accuracy of the vegetative and
minimally conscious state: Clinical consensus versus standardized neurobehavioral
assessment. BMC Neurology, 9(35), 1-5; Van Erp, W., Larvrijsen, J., Vos, P., Bor,
H., Laureys, S., & Koopmans, R. (2015). The vegetative state: Prevalence,
misdiagnosis and treatment limitations. JAMDA, 85, e9-85.e14. doi:
10.1016/j.jamda.2014.10.014 ). This indicates the continued need for careful
standardised assessment by skilled assessors to identify all potential meaningful
responses and to establish a correct and incontrovertible diagnosis. The Sensory
Modality Assessment and Rehabilitation Technique (SMART) is one of three
assessments identified for the assessment of PDOC in the Royal College of
Physician guidelines (Royal College of Physicians, 2013). The RCP guidelines and
recent publications have highlighted and substantiated the value of some of the
existing practices and unique features of the SMART. In recognition of the need
to keep SMART current, SMART Version 3 is being developed and will be launched
shortly. The interim SMART developments will be introduced in this paper and
applied to practice through the illustration of a case study. Evidence suggests
that SMART is a current and invaluable tool for the clinical and medico-legal
assessment and treatment of the PDOC patient.
PMID- 28420295
TI - Optimization of methotrexate loaded niosomes by Box-Behnken design: an
understanding of solvent effect and formulation variability.
AB - Dermal drug delivery system which localizes methotrexate (MTX) in the skin is
advantageous in topical treatment of psoriasis. The aim of the current study was
to understand dilution effects and formulation variability for the potential
formation of niosomes from proniosome gels of MTX. Box-Behnken's design was
employed to prepare a series of MTX proniosome gels of Span 40, cholesterol (Chol
X1) and Tween 20 (T20-X2). Short chain alcohols (X3), namely ethanol (Et),
propylene glycol (Pg) and glycerol (G) were evaluated for their dilution effects
on proniosomes. The responses investigated were niosomal vesicles size (Y1), MTX
entrapment efficiency percent (EE%-Y2) and zeta potential (Y3). MTX loaded
niosomes were formed immediately upon hydration of the proniosome gels with the
employed solvents. Addition of Pg resulted in a decrease of vesicular size from
534 nm to 420 nm as Chol percentage increased from 10% to 30%, respectively. In
addition, increasing the hydrophilicity of the employed solvents was enhancing
the resultant zeta potential. On the other hand, using Et in proniosomal gels
would abolish Chol action to increase the zeta potential value and hence less
stable niosomal dispersion was formed. The optimized formula of MTX loaded
niosomes showed vesicle size of 480 nm, high EE% (55%) and zeta potential of
25.5 mV, at Chol and T20 concentrations of 30% and 23.6%, respectively, when G
was employed as the solvent. Hence, G was the solvent of choice to prepare MTX
proniosomal gels with a maintained stability and highest entrapment.
PMID- 28420296
TI - The effect of engineered nanotopography of electrospun microfibers on fiber
rigidity and macrophage cytokine production.
AB - Currently, it is unknown how the mechanical properties of electrospun fibers, and
the presentation of surface nanotopography influence macrophage gene expression
and protein production. By further elucidating how specific fiber properties
(mechanical properties or surface properties) alter macrophage behavior, it may
be possible to create electrospun fiber scaffolds capable of initiating unique
cellular and tissue responses. In this study, we determined the elastic modulus
and rigidity of fibers with varying topographies created by finely controlling
humidity and including a non-solvent during electrospinning. In total,five fiber
scaffold types were produced. Analysis of fiber physical properties demonstrated
no change in fiber diameter amongst the five different fiber groups. However, the
four different fibrous scaffolds with nanopits or divots each possessed different
numbers of pits with different nanoscale dimensions. Unpolarized bone marrow
derived murine macrophages (M0), macrophages polarized towards a pro-inflammatory
phenotype (M1), or macrophages polarized towards anti-inflammatory phenotype
(M2b) were placed onto each of the scaffolds and cytokine RNA expression and
protein production were analyzed. Specific nanotopographies did not appreciably
alter cytokine production from undifferentiated macrophages (M0) or anti
inflammatory macrophages (M2b), but a specific fiber (with many small pits) did
increase IL-12 transcript and IL-12 protein production compared to fibers with
small divots. When analyzing the mechanical properties between fibers with divots
or with many small pits,divoted fibers possessed similar elastic moduli but
different stiffness values. In total,we present techniques capable of creating
unique electrospun fibers. These unique fibers have varying fiber mechanical
characteristics and modestly modulate macrophage cytokine expression.
PMID- 28420297
TI - The social trajectory of brain tumor: a qualitative metasynthesis.
AB - PURPOSE: Research indicates that strong social ties can buffer the adverse
effects of chronic illness on psychological well-being. Brain tumor typically
leads to serious functional impairments that affect relationships and reduce
social participation. This metasynthesis aimed to identify, appraise and
integrate the findings of qualitative studies that reveal the impact of brain
tumor on social networks. METHODS: Four major databases (PubMed, CINAHL, Cochrane
Library and PsycINFO) were systematically searched from inception to September
2016 for qualitative studies that reported findings on the impact of primary
brain tumor on social networks during adulthood. Twenty-one eligible studies were
identified and appraised according to the Consolidated Criteria for Reporting
Qualitative Research. Key findings of these studies were integrated to form
superordinate themes. RESULTS: The metasynthesis revealed the core themes of: 1)
Life disrupted; 2) Navigating the new reality of life; and 3) Social survivorship
versus separation. CONCLUSIONS: Multiple changes typically occur across the
social trajectory of brain tumor, including a loss of pre-illness networks and
the emergence of new ones. Understanding the barriers and facilitators for
maintaining social connection may guide interventions for strengthening social
networks and enhancing well-being in the context of brain tumor. Implications for
rehabilitation Social networks and roles are disrupted throughout the entire
trajectory of living with brain tumor Physical, cognitive and psychological
factors represent barriers to social integration Barriers to social integration
may be addressed by supportive care interventions Compensatory strategies,
adjusting goals and expectations, educating friends and family and accepting
support from others facilitate social reintegration throughout the trajectory of
living with brain tumor.
PMID- 28420298
TI - Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral
therapy or receiving a first-line treatment.
AB - BACKGROUND: The combination antiretroviral therapy (cART) has dramatically
improved the life expectancy of patients with HIV infection, but may lead to
several long-term metabolic abnormalities. However, data about the frequency of
metabolic syndrome (MS) in HIV-infected people vary considerably across different
observational studies. METHODS: The prevalence of MS among HIV-infected patients
was evaluated by a cross-sectional study conducted among subjects naive to cART
or receiving the first antiretroviral regimen and referring to our Clinics from
January 2015 to December 2015. The diagnosis of MS was made based on the National
Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and
International Diabetes Federation (IDF) criteria. RESULTS: The study recruited
586 patients: 98 naive to cART and 488 under the first antiretroviral treatment.
The prevalence of MS, according to NCEP-ATP III criteria, was significantly
higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014).
The most frequently reported components of MS among treated patients were high
triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and
hypertension (19.7%). On multivariate analysis, long duration of HIV infection,
low nadir of CD4 lymphocytes, high body mass index, current use of one protease
inhibitor, and long duration of cART were significantly associated with a higher
risk of MS, while current use of one integrase inhibitor was significantly
associated with a lower risk of MS. CONCLUSIONS: The non-negligible prevalence of
MS among HIV-infected patients under cART requires a careful and periodic
monitoring of its components, with particular attention to dyslipidemia and
hypertension.
PMID- 28420299
TI - Surface chemistry of gold nanoparticles determines the biocorona composition
impacting cellular uptake, toxicity and gene expression profiles in human
endothelial cells.
AB - This study investigated the role of nanoparticle size and surface chemistry on
biocorona composition and its effect on uptake, toxicity and cellular responses
in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold
nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and
polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona
proteins among the various AuNP, revealing largely surface chemistry-dependent
signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size
distribution analysis revealed the relative instability and aggregation inducing
potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular
dichroism analysis showed surface chemistry-dependent conformational changes of
proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and
HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC
formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI
AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological
pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC
BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP
by modulating expression of genes involved in DNA damage and repair, heat shock
response, mitochondrial energy metabolism, oxidative stress and antioxidant
response, and ER stress and unfolded protein response cascades, which were
aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is
shown to play the dominant role over size in determining the biocorona
composition, which in turn modulates cell uptake, and biological responses,
consequently defining the potential safety and efficacy of nanoformulations.
PMID- 28420300
TI - Epinephrine-induced pulmonary edema during hip arthroscopy: a report of two cases
and a review of the literature.
AB - OBJECTIVES: Hip arthroscopy utilization has significantly increased in recent
years. While it is a relatively safe procedure, it is not without risk. Life
threatening complications, albeit rare, can potentially occur and must be
appropriately recognized and treated. We describe 2 cases in which patients'
undergoing hip arthroscopy developed pulmonary edema and their respective courses
of treatment. METHODS: Both patients were being treated for symptomatic
femoroacetabular impingement (FAI), with labral tears, requiring operative
management after a failed trial of conservative management. The complication
occurred during a primary hip arthroscopy procedure and a retrospective review of
their clinical records and intra-operative notes was performed. RESULTS: Hip
arthroscopy was performed under spinal anesthetic in the supine position in both
patients. In both procedures, patients developed severe hypertension and
tachycardia, with subsequent oxygen desaturations with noted pulmonary edema. The
postulated etiology was systemic effects from intra-articular epinephrine,
causing acute pulmonary edema with corresponding cardiovascular changes. With
supportive ventilation, selective alpha-adrenergic blocker and furosemide
administration, and cessation of epinephrine exposure, vital signs normalized and
both patients experienced symptom resolution. CONCLUSION: During arthroscopy, if
acute hypertension, tachycardia and hypoxia develop, epinephrine-induced
pulmonary edema should be considered as a cause by the treating orthopedic
surgeon and anesthesiologist in order to initiate an appropriate treatment plan.
PMID- 28420301
TI - Seizures in Pediatric Patients With Liver Transplant and Efficacy of
Levetiracetam.
AB - The aim of this study was to evaluate the risk factors, clinical implications,
and prognosis of new-onset seizures that occurred after pediatric liver
transplantation, and to assess the efficacy of levetiracetam treatment. The
clinical and laboratory data of liver transplanted 28 children who had seizures
after liver transplantation and specifically of 18 children who received
levetiracetam were analyzed retrospectively. Sixteen patients (88.9%) remained
seizure-free and in 2 (11.1%), more than 50% reduction in seizures were detected
with levetiracetam treatment. In conclusion, seizures are generally the most
common complication by a spectrum of seizure types, and sometimes cause
symptomatic epilepsy. The most common risk factors for seizures in transplant
recipients is immunosuppressant toxicity. Currently, there isn't a specific
treatment involving the transplant patient population. Levetiracetam may be
preferable in pediatric patients as it's reliable for liver disease and has
advantages in the treatment of postoperative seizures due to its intravenous
usage.
PMID- 28420302
TI - The Genus Spirorchis MacCallum, 1918 (Digenea: Schistosomatoidea) and the Early
History of Parasitology in the United States.
AB - We know little about the founders of our discipline apart from their scientific
contributions and brief biographical sketches, most frequently in published
obituaries. A number of years ago, Ralph Lichtenfels, then Director of the
National Parasite Collection, sent me photocopies of letters between Henry
Baldwin Ward, Horace W. Stunkard, George A. MacCallum, and William G. MacCallum
dating from the early years of the 20th century that hinted at a series of
conflicts centered on the proposal of Spirorchis MacCallum, 1918 (Digenea:
Schistosomatoidea). The description of a fluke that matured in the blood of a
tetrapod and that was morphologically similar to the schistosomes of humans was
in its time a transformative discovery; and the scientist who published it would
have garnered some scholarly recognition. Herein, I provide an historical account
of the issues and the motives of each individual and the eventual resolution of
these matters.
PMID- 28420303
TI - Juvenile Papillomatosis (Swiss-Cheese Disease) of Breast in an Adult Male With
Sequential Diagnoses of Ipsilateral Intraductal, Invasive, and Widely Metastatic
Carcinoma: A Case Report and Review of the Disease in Males.
AB - Juvenile papillomatosis of the breast (JPB, also known as Swiss cheese disease)
is a rare ailment that typically afflicts young females, and presents as a mass
forming lesion. The lesional mass usually comprises multiple cysts and duct
stasis, amid a variety of proliferative and nonproliferative epithelial changes.
The proliferative changes include papillary hyperplasia, florid hyperplasia, and
papillary apocrine hyperplasia. Concurrent carcinoma (either in situ or invasive)
is present in approximately 10% of cases at presentation, and subsequent
carcinoma (either in situ or invasive) is diagnosed in about 10% of patients.
About 20% of patients have a strong family history of breast carcinoma. A total
of 10 cases of JPB have been previously reported in males, both children and
adults, only one of which, in a 33-year-old, was associated with invasive
carcinoma. Here, another case of JPB in a 45-year-old male-one with subsequent
sequential diagnoses of ipsilateral intraductal carcinoma, invasive carcinoma,
and widely metastatic carcinoma over the course of 15 years-is reported.
PMID- 28420304
TI - Ectopic Pacinian Corpuscle in the Prostate.
PMID- 28420305
TI - Dual Pathology: Double Trouble in a Colonic Biopsy.
PMID- 28420306
TI - Diffuse Large B-Cell Lymphoma in a Patient With Necrotizing Fasciitis Secondary
to Silicone Biopolymer Implants in Buttock.
PMID- 28420307
TI - Adapting the revised prenatal coping inventory (NuPCI) for use in a Spanish
population.
AB - OBJECTIVE: To adapt the Revised Prenatal Coping Inventory (NuPCI) for the
evaluation of prenatal stress coping strategies utilised by Spanish women.
METHODS: A cross-sectional study was performed to evaluate the psychometric
properties of NuPCI adapted for a Spanish population. Two hundred and sixty one
puerperium women completed the NuPCI at the time of discharge after childbirth.
Instrument construct validity was evaluated using subscale item correlations.
Internal consistency was assessed using Cronbach's alpha test. RESULTS: Items
from each subscale (Preparation, Avoidance and Spiritual - Positive Coping) were
significantly correlated with the global result (p < .001). The internal
reliability of the NuPCI demonstrated suitable values for each of the three
coping strategies (alpha > 0.7). The most frequently used coping strategy was
Preparation and the least used was Avoidance. Utilisation of the coping
strategies with Preparation decreased with increasing parity (p = .002) and
greater prenatal stress was associated with increased use of the Avoidance coping
strategy (p < .001). CONCLUSIONS: The NuPCI adapted for Spanish women
demonstrates good psychometric properties for evaluating the three types of
prenatal stress coping strategies: Preparation, Avoidance and Spiritual -
Positive Coping. Results were similar to those presented by the instrument in its
English language version.
PMID- 28420308
TI - Nanodispersion-loaded mucoadhesive polymeric inserts for prolonged treatment of
post-operative ocular inflammation.
AB - Mucoadhesive polymeric films incorporated with ketorolac tromethamine-loaded
nanodispersion aiming the sustained delivery of the drug to the cornea have been
developed and characterised for the treatment of post-operative ocular
inflammation. Nanodispersions were prepared by ionic gelation method with various
concentrations of chitosan and sodium tripolyphosphate. The developed
nanodispersions were analysed for morphology, particle size, dispersion
homogeneity, zeta potential, entrapment efficiency and drug release. The
nanodispersion that showed the smallest particle size and the highest entrapment
efficiency was incorporated in optimised HPMC E15 and Eudragit RL100/HPMC K4m
films. The formulation with optimum physicomechanical properties was selected to
study its ex vivo transcorneal permeation through freshly excised bovine cornea
in comparison with the nanodispersion and the marketed eye drops (Acular(r)). The
polymeric ocular film showed greater permeation than aqueous eye drops. Moreover,
the ocular film revealed a prolonged anti-inflammatory effect compared to eye
drops when applied to inflamed rabbit's eyes.
PMID- 28420310
TI - Helminth Fauna Associated with Three Neotropical Bat Species (Chiroptera:
Mormoopidae) in Veracruz, Mexico.
AB - Bats are recognized as potential hosts of pathogens exploiting the food chain to
reach them as definitive hosts. However, very little is known about their
endoparasites, especially for Neotropical bats. In this study, we assessed the
helminth fauna associated with 3 insectivorous bat species roosting in the same
single hot cave in central Veracruz, Mexico: Mormoops megalophylla, Pteronotus
davyi, and Pteronotus personatus. During a period of 1 yr (April 2007-2008), 135
mormoopid bats in total were collected and examined for helminths. Six parasite
species representing 3 types of intestinal helminths were found: 1 cestode
Vampirolepis elongatus; 2 trematodes Maxbraunium tubiporum and Ochoterenatrema
labda; and 3 nematodes Linustrongylus pteronoti, Molineidae gen. sp., and
Capillaria sp. Overall, trematodes were the most abundant parasite group (72.4%),
followed by nematodes (20.7%) and cestodes (6.9%). Species-accumulation curves
suggest that the worms collected (n = 1,331) from these 6 parasite species
comprise the helminth fauna associated with the 3 bat populations studied. The
only species shared by the 3 bat species was Capillaria sp. Most (5/6) of the
helminth species recorded use Lepidoptera and Diptera as intermediate hosts;
therefore, diet is likely the main source of infection. Although insectivorous
bats are considered dietary generalist species, the differences found in helminth
diversity in these sympatric populations of closely related bat species, suggest
that diet partitioning occurs in mormoopid bat communities. Helminths tend to
exploit the food chain to reach their final hosts; therefore, studying these
parasites can provide useful information to further understand the biology of
bats.
PMID- 28420309
TI - A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using
a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior
Cingulate Cortex and the Left Cerebellum.
AB - The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We
used proton magnetic resonance spectroscopy to investigate metabolite
concentration ratios in the anterior cingulate cortex and left cerebellum in ASD.
In the ACC and left cerebellum studies, the ASD group and intelligence quotient-
and age-matched control group consisted of 112 and 114 subjects and 65 and 45
subjects, respectively. In the ASD group, gamma-aminobutyric acid (GABA)+/
creatine/phosphocreatine (Cr) was significantly decreased in the anterior
cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr
was significantly decreased in the left cerebellum compared to those in the
control group. In addition, both groups showed negative correlations between
Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between
GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have
hypoGABAergic alterations in the anterior cingulate cortex and
hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.
PMID- 28420311
TI - Exploring the effect of formulation parameters on the particle size of
carboxymethyl chitosan nanoparticles prepared via reverse micellar crosslinking.
AB - Carboxymethyl chitosan (CMCh), as a non-toxic, biocompatible and biodegradable
semi-synthetic biopolymer with mucoadhesive properties, is widely investigated
for targeting drug or gene delivery applications. Here, fabrication of CMCh
nanoparticles will be reported using a reverse (w/o) micellar system to provide
particles with tuneable mean sizes. Reverse microemulsions were prepared by
dispersing aqueous solution of CMCh in n-hexane using sodium-bis(ethylhexyl)
sulfosuccinate (AOT) and glutaraldehyde (GA) as an emulsifier and a crosslinking
agent, respectively. The obtained particles were perfectly spherical in the
nanometric size range (40-140 nm) with a narrow size distribution according to
the FE-SEM images. To determine the effective parameters on the mean nanosphere
size, CMCh, AOT and GA concentrations were varied according to a full-factorial,
three-level design-of-experiments. After evaluating the results, it was found
that AOT and CMCh concentrations had a significant effect on the mean nanosphere
size while GA concentration surprisingly showed non-significant, minor effects on
the same response.
PMID- 28420312
TI - Delivering E-lectures effectively and efficiently using Google DriveTM.
PMID- 28420315
TI - Dental care attendance and refrainment from dental care among adults.
AB - OBJECTIVE: The aim of this study was to analyse dental care utilization,
refrainment from self-perceived needed dental care and the association with
socioeconomic indicators among adult individuals. MATERIALS AND METHODS: This
cross-sectional survey included 3500 randomly selected adult individuals.
Telephone interviews were conducted and the participants answered a battery of
questions regarding dental visiting habits, health, socioeconomic position (SEP),
behavioural factors and lifestyle indicators. RESULTS: The outcome 'dental
visits' was significantly correlated with SEP, especially with monetary
dimensions, such as income and economic resources for unforeseen expenditures.
However, educational level was not a significant predictor in the tested
statistical models. Furthermore, other covariates that contributed significantly
to the models were ethnicity, dental anxiety and lifestyle factors, albeit with a
different pattern of impact on the two outcome dimensions. Important features of
the SEP variables were the stepwise gradient relative to the outcomes,
implicating that the lower the SEP status, the greater the risk of reporting
irregular dental visiting habits and refraining from dental care due to financial
problems. CONCLUSIONS: Dental care utilization and refraining from dental care
for financial reasons clearly reveal associations with socioeconomic positions
among adult individuals.
PMID- 28420316
TI - Persistence of secondary prevention medication and related factors for acute
ischemic stroke and transient ischemic attack in China.
AB - OBJECTIVE: We recently measured the longitudinal use of secondary prevention
medication following hospital discharge and the factors influencing persistence
in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA)
in China. METHODS: Patients with AIS and TIA who were enrolled in the China
National Stroke Registry II from June 2012 to January 2013 were surveyed to
determine persistence. The medications included antiplatelet therapies, warfarin,
antihypertensive therapies, statins, and diabetes medications. We determined
persistence for a three-month period following discharge. Persistence was defined
as the continuation of all secondary preventive medications prescribed upon
hospital discharge. The factors associated with medication persistence 3 months
after discharge were examined using a multivariable logistic regression. RESULTS:
Of the 21,592 patients with AIS and TIA, 18,344 (91.2%) were eligible for
analysis. After 3 months post-discharge, 46.2% of the subjects continued to take
all secondary prevention medications prescribed at discharge. Independent
predictors of three-month medication persistence included younger age, absence of
a history of diabetes or atrial fibrillation, higher family income, less severe
stroke, index cerebrovascular event of ischemic stroke, and being treated in a
hospital with a stroke unit and more beds in the neurology department.
CONCLUSIONS: More than half of patients with AIS and TIA reported discontinuing
one or more secondary prevention medications within 3 months of hospital
discharge. Several factors associated with medication persistence were
identified. Here, we propose strategies that could be implemented to improve the
quality of secondary prevention.
PMID- 28420317
TI - The role of coherence of mind and reflective functioning in understanding binge
eating disorder and co-morbid overweight.
AB - Coherence of mind and reflective functioning may impact negative affect and
interpersonal functioning over and above the effects of symptoms of depression
and interpersonal problems that contribute to symptoms of binge-eating disorder
(BED) and overweight/obesity. Matched samples of overweight women with BED and
overweight and normal weight women without BED completed the Adult Attachment
Interview, a measure of depressive symptoms, and a measure of interpersonal
problems. Greater symptoms of depression distinguished women with BED from the
matched comparison samples. Greater interpersonal problems differentiated women
with BED from overweight women without BED. Coherence of Mind scores did not
differentiate the samples. However, lower Reflective Functioning scores did
distinguish both women with BED and overweight women without BED from normal
weight women. Lower reflective functioning may lead to binge eating independent
of depressive symptoms and interpersonal problems.
PMID- 28420318
TI - Advancing Clinicopathologic Diagnosis of High-risk Neuroblastoma Using
Computerized Image Analysis and Proteomic Profiling.
AB - A subset of patients with neuroblastoma are at extremely high risk for treatment
failure, though they are not identifiable at diagnosis and therefore have the
highest mortality with conventional treatment approaches. Despite tremendous
understanding of clinical and biological features that correlate with prognosis,
neuroblastoma at ultra-high risk for treatment failure remains a diagnostic
challenge. As a first step towards improving prognostic risk stratification
within the high-risk group of patients, we determined the feasibility of using
computerized image analysis and proteomic profiling on single slides from
diagnostic tissue specimens. After expert pathologist review of tumor sections to
ensure quality and representative material input, we evaluated multiple regions
of single slides as well as multiple sections from different patients' tumors
using computational histologic analysis and semiquantitative proteomic profiling.
We found that both approaches determined that intertumor heterogeneity was
greater than intratumor heterogeneity. Unbiased clustering of samples was
greatest within a tumor, suggesting a single section can be representative of the
tumor as a whole. There is expected heterogeneity between tumor samples from
different individuals with a high degree of similarity among specimens derived
from the same patient. Both techniques are novel to supplement pathologist review
of neuroblastoma for refined risk stratification, particularly since we
demonstrate these results using only a single slide derived from what is usually
a scarce tissue resource. Due to limitations of traditional approaches for
upfront stratification, integration of new modalities with data derived from one
section of tumor hold promise as tools to improve outcomes.
PMID- 28420319
TI - BCOR-CCNB3 Undifferentiated Sarcoma-Does Immunohistochemistry Help in the
Identification?
AB - Recent methodology has enabled the identification of some new genetic subgroups
within the melting pot of lesions presently classified by the 2013 WHO
classification as "undifferentiated/unclassified sarcomas". One of these
subgroups is characterized by a paracentric inversion of the X chromosome with
consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features
of these tumors overlap with the Ewing sarcoma family as well as other soft
tissue sarcomas, thus making them difficult to diagnose. To investigate the
morphological and immunohistochemical characteristics of BCOR-CCNB3 positive
sarcoma, we reviewed two sarcoma series, comprising 632 and 121 cases. The 11
tumors harboring the BCOR-CCNB3 fusion, identified by CCNB3 immunohistochemistry
and/or RT-PCR, were reevaluated for morphological characteristics and further
immunohistochemical investigations for CCNB3, SATB2, and Pax8 were performed.
Tumors harboring a BCOR-CCNB3 fusion (11/753) occured exclusively in males, with
a mean age at diagnosis of 12.9 years, and were mainly axially located. In this
group of either spindled or round cell tumors, vesicular nuclei with finely
dispersed chromatin, inconspicuous nucleoli and an arciform vascular pattern were
pathognomonic. More than 50% of cases stained positive for SATB2 and Pax8,
raising the hypothesis of a potential use of these markers in the identification
of BCOR-CCNB3 positive undifferentiated/unclassified sarcomas. CCNB3 was
confirmed as a useful ancillary immunohistochemical marker.
PMID- 28420320
TI - Pediatric Non-vestibular Schwannoma.
AB - While the clinicopathologic features of pediatric vestibular schwannomas, often
in the context of neurofibromatosis type 2 (NF2), have been well studied, there
is less data regarding the characteristics of pediatric non-vestibular
schwannomas (NVS). Additionally, the rate of loss of SMARCB1/INI1 expression in
this population has not been systematically evaluated. Our institutional archives
were searched for cases of NVS arising in patients 18 years or younger.
Clinicopathologic features including SMARCB1/INI1 status were assessed for each
case. Twenty-three NVS from 9 males and 13 females (age range, 2 months to 18
years) were identified, and sites included paraspinal (n = 10), head and neck (n
= 6), extremities (n = 4), trunk (n = 1), mediastinum (n = 1), and
retroperitoneum (n = 1); 22 cases were Antoni A predominant with 6 cases
comprising solely Antoni A tissue. The mitotic rate of the tumors ranged from 0
to 10/10 high-power fields (HPFs), and 3 tumors had mitotic rates of >=4
mitoses/10 HPFs. Two tumors showed plexiform architecture. No NVS showed diffuse
atypia, calcifications, microcystic/reticular architecture, epithelioid
morphology, pseudoglandular change, neuroblastoma-like features, or necrosis. All
tumors tested (23/23) showed retained nuclear expression of SMARCB1/INI1. Follow
up was available in 21 patients (range 1 week to 194 months), and 5 tumors
recurred. Pediatric NVS have a relatively homogeneous appearance with a
predominance of Antoni A areas. Pathologists should be aware that schwannomas in
this age group may be cellular with mitotic rates of >=4/10 HPFs to avoid
misclassification as a spindle cell sarcoma.
PMID- 28420321
TI - Submucosal Colonic Lipoblastoma Presenting With Colo-colonic Intussusception in
an Infant.
AB - Lipoblastoma is a benign adipose tumor typically presenting in infancy in
superficial soft tissues of extremities. Intestinal complications secondary to
intraabdominal or retroperitoneal involvement are exceedingly rare. We describe a
unique case of a primary intestinal lipoblastoma arising from the submucosa of
the transverse colon in an otherwise healthy 18-month-old boy. He presented with
a history of reducible rectal prolapse, rectal bleeding, and episodic abdominal
pain and was initially treated for constipation. Imaging identified a short colo
colonic intussusception, confirmed at laparotomy, and a fatty mass thought to
arise from the mesentery. Pathological examination of the resected transverse
colon revealed a submucosal tumor composed of a mixture of mature adipose tissue,
foci of myxoid mesenchymal tissue with desmin positive, HMGA2 negative spindle
cells, and scattered lipoblasts, characteristic of lipoblastoma. Lipoblastoma
should be considered as a potential albeit rare cause of intussusception in young
children, where a pathologic lead point is infrequently identified.
PMID- 28420322
TI - Epidemiology of paediatric renal stone disease: a 22-year single centre
experience in the UK.
AB - BACKGROUND: Whilst still rare, the incidence of paediatric stone disease is
increasing in developed countries and it is important to evaluate the aetiology.
We set up a dedicated renal stone service for children combining medical and
surgical expertise in 1993 and now have a large case series of children to
investigate the epidemiology. METHODS: A retrospective hospital note review of
children presenting with kidney stones during the last 22 years (1993-2015) was
conducted. All patients had a comprehensive infective and metabolic screen and
were classified as metabolic, infective or idiopathic stone disease. RESULTS:
Five hundred eleven patients (322 male) were reviewed. The median age of
presentation was 4.4y for males (1 m-16.6y) and 7.3y (1-18.5y) for females with a
median height and weight on the 25th centile for male and on 10th and 25th for
female, respectively. One hundred seventy five (34%) had an underlying metabolic
abnormality, 112 (22%) had infective stones and 224 (44%) were classified as
idiopathic. Of the 175 patients with a metabolic abnormality: 91 (52%) had
hypercalciuria (76 persistent and 15 transient), 37 (21%) hyperoxaluria, 38 (22%)
cystinuria, 3 (2%) abnormalities in the purine metabolism and the remainder other
metabolic abnormalities. Bilateral stones occurred in 27% of the metabolic group
compared to 16% in the non-metabolic group (OR 0.2, p < 0.05). Urinary tract
infection was a common complication (27%) in the metabolic group. CONCLUSIONS: In
this paper, we present the largest cohort of paediatric stone disease reported
from a developed country giving details on both, clinical and laboratory data. We
show that in the majority of the patients there is an identifiable underlying
metabolic and/or infective aetiology emphasizing the importance of a full work up
to provide adequate treatment and prevent recurrence. Moreover, we show that
stone disease in children, in contrast to the adult population, does not seem to
be associated with obesity, as children have a weight below average at
presentation.
PMID- 28420324
TI - Evaluation of a technology-enhanced integrated care model for frail older
persons: protocol of the SPEC study, a stepped-wedge cluster randomized trial in
nursing homes.
AB - BACKGROUND: Limited evidence exists on the effectiveness of the chronic care
model for people with multimorbidity. This study aims to evaluate the
effectiveness of an information and communication technology- (ICT-)enhanced
integrated care model, called Systems for Person-centered Elder Care (SPEC), for
frail older adults at nursing homes. METHODS/DESIGN: SPEC is a prospective
stepped-wedge cluster randomized trial conducted at 10 nursing homes in South
Korea. Residents aged 65 or older meeting the inclusion/exclusion criteria in all
the homes are eligible to participate. The multifaceted SPEC intervention, a
geriatric care model guided by the chronic care model, consists of five
components: comprehensive geriatric assessment for need/risk profiling,
individual need-based care planning, interdisciplinary case conferences, person
centered care coordination, and a cloud-based information and communications
technology (ICT) tool supporting the intervention process. The primary outcome is
quality of care for older residents using a composite measure of quality
indicators from the interRAI LTCF assessment system. Outcome assessors and data
analysts will be blinded to group assignment. Secondary outcomes include quality
of life, healthcare utilization, and cost. Process evaluation will be also
conducted. DISCUSSION: This study is expected to provide important new evidence
on the effectiveness, cost-effectiveness, and implementation process of an ICT
supported chronic care model for older persons with multiple chronic illnesses.
The SPEC intervention is also unique as the first registered trial implementing
an integrated care model using technology to promote person-centered care for
frail older nursing home residents in South Korea, where formal LTC was recently
introduced. TRIAL REGISTRATION: ISRCTN11972147.
PMID- 28420325
TI - Usefulness of grayscale inverted images in addition to standard images in digital
mammography.
AB - BACKGROUND: Mammography is essential for early diagnosis of breast cancer, which
is the most common type of cancer in females that is associated with a high
mortality rate. We investigated whether evaluation of the grayscale inverted
images of mammograms would aid in increasing the diagnostic sensitivity of the
mammographic imaging technique. METHODS: Our study included 636 mammograms of 159
women who had undergone digital mammography. Standard, grayscale inverted, and
standard plus grayscale inverted images were sequentially examined three times,
at 15-day intervals, for the presence or assessment of pathological changes in
the skin, calcification, asymmetric density, mass lesions, structural
distortions, and intramammary and axillary lymph nodes. To determine whether
grayscale inverted image assessment improved detection rates, the results of the
three assessment modes were compared using Cochran's Q test and the McNemar test
(p < 0.05 was considered statistically significant). RESULTS: The average age of
159 patients was 50.4 years (range, 35-80 years). There were significant
differences among the three assessment modes with respect to calcification and
intramammary lymph nodes (p < 0.05); however, no significant differences were
observed for the detection of other parameters. CONCLUSIONS: Assessment of
grayscale inverted images in addition to standard images facilitates the
detection of microcalcification.
PMID- 28420323
TI - Study protocol: Insight 46 - a neuroscience sub-study of the MRC National Survey
of Health and Development.
AB - BACKGROUND: Increasing age is the biggest risk factor for dementia, of which
Alzheimer's disease is the commonest cause. The pathological changes underpinning
Alzheimer's disease are thought to develop at least a decade prior to the onset
of symptoms. Molecular positron emission tomography and multi-modal magnetic
resonance imaging allow key pathological processes underpinning cognitive
impairment - including beta-amyloid depostion, vascular disease, network
breakdown and atrophy - to be assessed repeatedly and non-invasively. This
enables potential determinants of dementia to be delineated earlier, and
therefore opens a pre-symptomatic window where intervention may prevent the onset
of cognitive symptoms. METHODS/DESIGN: This paper outlines the clinical,
cognitive and imaging protocol of "Insight 46", a neuroscience sub-study of the
MRC National Survey of Health and Development. This is one of the oldest British
birth cohort studies and has followed 5362 individuals since their birth in
England, Scotland and Wales during one week in March 1946. These individuals have
been tracked in 24 waves of data collection incorporating a wide range of health
and functional measures, including repeat measures of cognitive function. Now
aged 71 years, a small fraction have overt dementia, but estimates suggest that
~1/3 of individuals in this age group may be in the preclinical stages of
Alzheimer's disease. Insight 46 is recruiting 500 study members selected at
random from those who attended a clinical visit at 60-64 years and on whom
relevant lifecourse data are available. We describe the sub-study design and
protocol which involves a prospective two time-point (0, 24 month) data
collection covering clinical, neuropsychological, beta-amyloid positron emission
tomography and magnetic resonance imaging, biomarker and genetic information.
Data collection started in 2015 (age 69) and aims to be completed in 2019 (age
73). DISCUSSION: Through the integration of data on the socioeconomic environment
and on physical, psychological and cognitive function from 0 to 69 years, coupled
with genetics, structural and molecular imaging, and intensive cognitive and
neurological phenotyping, Insight 46 aims to identify lifetime factors which
influence brain health and cognitive ageing, with particular focus on Alzheimer's
disease and cerebrovascular disease. This will provide an evidence base for the
rational design of disease-modifying trials.
PMID- 28420326
TI - Transcriptional changes induced by bevacizumab combination therapy in responding
and non-responding recurrent glioblastoma patients.
AB - BACKGROUND: Bevacizumab combined with chemotherapy produces clinical durable
response in 25-30% of recurrent glioblastoma patients. This group of patients has
shown improved survival and quality of life. The aim of this study was to
investigate changes in gene expression associated with response and resistance to
bevacizumab combination therapy. METHODS: Recurrent glioblastoma patients who had
biomarker-accessible tumor tissue surgically removed both before bevacizumab
treatment and at time of progression were included. Patients were grouped into
responders (n = 7) and non-responders (n = 14). Gene expression profiling of
formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.
RESULTS: By comparing pretreatment samples of responders with those of non
responders no significant difference was observed. In a paired comparison
analysis of pre- and posttreatment samples of non-responders 1 gene was
significantly differentially expressed. In responders, this approach revealed 256
significantly differentially expressed genes (72 down- and 184 up-regulated genes
at the time of progression). Genes differentially expressed in responders
revealed a shift towards a more proneural and less mesenchymal phenotype at the
time of progression. CONCLUSIONS: Bevacizumab combination treatment demonstrated
a significant impact on the transcriptional changes in responders; but only
minimal changes in non-responders. This suggests that non-responding
glioblastomas progress chaotically without following distinct gene expression
changes while responding tumors adaptively respond or progress by means of the
same transcriptional changes. In conclusion, we hypothesize that the identified
gene expression changes of responding tumors are associated to bevacizumab
response or resistance mechanisms.
PMID- 28420327
TI - Clinical predictors for the prognosis of myasthenia gravis.
AB - BACKGROUND: Clinical predictors for myasthenia gravis relapse and ocular
myasthenia gravis secondary generalization during the first two years after
disease onset remain incompletely identified. This study attempts to investigate
the clinical predictors for the prognosis of Myasthenia Gravis. METHODS: Eighty
three patients with myasthenia gravis were concluded in this study. Baseline
characteristics were analyzed as predictors. RESULTS: Relapse of myasthenia
gravis developed in 26 patients (34%). Generalization developed in 34 ocular
myasthenia gravis patients (85%). Other autoimmune diseases were observed more
commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group
contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients
with thymus hyperplasia progressed more rapidly than those with other thymus
pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as
ptosis or diplopia predicted early progression than concurrence of ptosis and
diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine,
thymectomy, IVIG, immunosuppressive drugs did not show significant difference
between the relapsed and non-relapsed groups. The treatment outcome also showed
no difference between the single OMG and second generalized groups. CONCLUSIONS:
Occurrence of associated autoimmune disease can serve as a potential predictor
for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic
hyperplasia can predict generalization in the first six months.
PMID- 28420328
TI - Talking about intimate partner violence in multi-cultural antenatal care: a
qualitative study of pregnant women's advice for better communication in South
East Norway.
AB - BACKGROUND: Intimate partner violence (IPV) against women constitutes a major
public health problem. Antenatal care is considered a window of opportunity to
disclose and to communicate about IPV. However, little is known about how women
from different ethnic backgrounds wish to communicate about their experiences
with IPV during pregnancy in antenatal care. The aim of the present study was to
explore how women from different ethnic backgrounds experienced IPV and what
their recommendations were about how midwives should communicate about IPV in
antenatal care. METHODS: Qualitative individual interviews with eight women who
had experienced IPV during pregnancy were conducted and analysed using thematic
analysis. The participants were purposively recruited from three crisis shelters
in South-East Norway. RESULTS: The participants either had immigrant backgrounds
(n = 5) or were ethnic Norwegians (n = 3). All participants received antenatal
care by a midwife. Although none of the participants were asked about IPV during
antenatal care, they wished to talk about their experiences. Most participants
felt that it would be important for the midwife to make them aware that they were
victims of violence. Participants offered different suggestions on how and when
midwives should talk about IPV. Facilitators to talk about IPV with the midwife
were a good relationship with and the trustworthiness of the midwife, information
about possible negative health outcomes for the newborn owing to IPV and knowing
that the midwife could help them. The main barriers to talk about IPV with the
midwife were that the participants were accompanied by their husbands during
antenatal care, fear that the Child Welfare Service would take away their
children after disclosure and cultural acceptance of violence. Participants with
immigrant backgrounds also experienced difficulties in talking about IPV owing to
their limited language skills. They thought that professionally trained
interpreters with experience of IPV could overcome this barrier. CONCLUSION: Even
though none of the participants were asked about IPV in antenatal care, they
offered different suggestions on how and when midwives should talk about IPV.
Participants irrespective of their ethnical backgrounds perceived antenatal care
as a key area to facilitate disclosure of IPV. Midwives' communication and
strategic skills to address IPV are crucial for help-seeking women. Training
midwives' skills in culture-sensitive communication might help to overcome
cultural barriers to talk about violence.
PMID- 28420329
TI - Contrast-enhanced US with Perfluorobutane(Sonazoid) used as a surveillance test
for Hepatocellular Carcinoma (HCC) in Cirrhosis (SCAN): an exploratory cross
sectional study for a diagnostic trial.
AB - BACKGROUND: Ultrasonography (US) is widely used as a standard surveillance tool
for patients who are at a high risk of having hepatocellular carcinoma (HCC);
however, conventional B-mode US appears to be insufficient in order to ensure the
early detection of HCC. Perfluorobutane allows very stable Kupffer phase imaging
for at least 60 min, which is tolerable for examinations of the entire liver. The
purpose of our study is to evaluate the added value of contrast-enhanced US using
perfluorobutane to that of conventional B-mode US as an HCC surveillance tool for
patients with liver cirrhosis. METHODS/DESIGN: SCAN (Sonazoid-US for surveillance
of hepatoCellulArcarciNoma) is a prospective, multi-institutional, diagnostic
trial using an intra-individual comparison design in a single arm of patients.
This study was approved by our five institutional review board and informed
consent was obtained from all participating. We obtained consent for publication
of these data (contrast enhanced US images, CT or MRI images, laboratory
findings, age, sex) from all participating patients. All patients will undergo
conventional B-mode US immediately followed by contrast-enhanced US. The
standardized case report forms will be completed by operating radiologists after
B-mode US and contrast-enhanced US, respectively. If any lesion(s) is detected,
the likelihood of HCC will be recorded. The primary endpoints are a detection
rate of early-stage HCC and a false referral rate of HCC. Intra-individual
comparison using Mcnemar's test will be performed between B-mode US and contrast
enhanced US. The study will include 523 patients under HCC surveillance in five
medical institutions in Korea. DISCUSSION: SCAN is the first study to investigate
the efficacy of contrast-enhanced US in surveillance using two reciprocal
endpoints specialized for the evaluation of a surveillance test. SCAN will
provide evidence regarding whether patients can truly benefit from contrast
enhanced US in terms of the detection of early stage HCC while avoiding
additional unnecessary examinations. In addition to the study protocol, we
elaborate on potentially debatable components of SCAN, including the design of an
intra-individual comparison study, study endpoints, composite reference
standards, and indefinite imaging criteria regarding the likelihood of HCC. TRIAL
REGISTRATION: The date of trial registration (ClincalTrials.gov: NCT02188901 ) in
this study is July 3, 2014. The last patient enrolled in August 30, 2016 and
follow up to see the primary end point is still ongoing. All authors have no
other relationships/conditions/circumstances that present a potential conflict of
interest of relationships. Our study protocol has undergone peer-review by the
funding body (GE Healthcare). No other relationships/conditions/circumstances
that present a potential conflict of interest. Also, we clearly stated in the
'competing interests' section of my manuscript.
PMID- 28420330
TI - Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a
primary EBV infection: a case report.
AB - BACKGROUND: Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are
detected in various demyelinating diseases, such as pediatric acute disseminated
encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody
seronegative neuromyelitis optica spectrum disorder. We present a patient who
developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM)
due to Epstein-Barr virus (EBV) infection. CASE PRESENTATION: A 36-year-old
healthy man developed paresthesia of bilateral lower extremities and urinary
retention 8 days after the onset of IM due to primary EBV infection. The MRI
revealed the lesions in the cervical spinal cord, the conus medullaris, and the
internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis.
Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of
1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly
improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG
antibody titer at the 6-month follow-up was negative. CONCLUSIONS: This case
suggests that primary EBV infection would trigger anti-MOG antibody-positive
ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of
which correlate well with the neurological symptoms.
PMID- 28420331
TI - Arsenic treatment increase Aurora-A overexpression through E2F1 activation in
bladder cells.
AB - BACKGROUND: Arsenic is a widely distributed metalloid compound that has biphasic
effects on cultured cells. In large doses, arsenic can be toxic enough to trigger
cell death. In smaller amounts, non-toxic doses may promote cell proliferation
and induces carcinogenesis. Aberration of chromosome is frequently detected in
epithelial cells and lymphocytes of individuals from arsenic contaminated areas.
Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability
and cell transformation. We have reported that low concentration (?1 MUM) of
arsenic treatment increases Aurora-A expression in immortalized bladder
urothelial E7 cells. However, how arsenic induces carcinogenesis through Aurora-A
activation remaining unclear. METHODS: Bromodeoxyuridine (BrdU) staining, MTT
assay, and flow cytometry assay were conducted to determine cell proliferation.
Messenger RNA and protein expression levels of Aurora-A were detected by reverse
transcriptional-PCR and Western blotting, respectively. Centrosome of cells was
observed by immunofluorescent staining. The transcription factor of Aurora-A was
investigated by promoter activity, chromosome immunoprecipitation (ChIP), and
small interfering RNA (shRNA) assays. Mouse model was utilized to confirm the
relationship between arsenic and Aurora-A. RESULTS: We reveal that low dosage of
arsenic treatment increased cell proliferation is associated with accumulated
cell population at S phase. We also detected increased Aurora-A expression at
mRNA and protein levels in immortalized bladder urothelial E7 cells exposed to
low doses of arsenic. Arsenic-treated cells displayed increased multiple
centrosome which is resulted from overexpressed Aurora-A. Furthermore, the
transcription factor, E2F1, is responsible for Aurora-A overexpression after
arsenic treatment. We further disclosed that Aurora-A expression and cell
proliferation were increased in bladder and uterus tissues of the BALB/c mice
after long-term arsenic (1 mg/L) exposure for 2 months. CONCLUSION: We reveal
that low dose of arsenic induced cell proliferation is through Aurora-A
overexpression, which is transcriptionally regulated by E2F1 both in vitro and in
vivo. Our findings disclose a new possibility that arsenic at low concentration
activates Aurora-A to induce carcinogenesis.
PMID- 28420332
TI - Genetic diversity of Elaeis oleifera (HBK) Cortes populations using cross species
SSRs: implication's for germplasm utilization and conservation.
AB - BACKGROUND: The Elaeis oleifera genetic materials were assembled from its center
of diversity in South and Central America. These materials are currently being
preserved in Malaysia as ex situ living collections. Maintaining such collections
is expensive and requires sizable land. Information on the genetic diversity of
these collections can help achieve efficient conservation via maintenance of core
collection. For this purpose, we have applied fourteen unlinked microsatellite
markers to evaluate 532 E. oleifera palms representing 19 populations distributed
across Honduras, Costa Rica, Panama and Colombia. RESULTS: In general, the
genetic diversity decreased from Costa Rica towards the north (Honduras) and
south-east (Colombia). Principle coordinate analysis (PCoA) showed a single
cluster indicating low divergence among palms. The phylogenetic tree and
STRUCTURE analysis revealed clusters based on country of origin, indicating
considerable gene flow among populations within countries. Based on the values of
the genetic diversity parameters, some genetically diverse populations could be
identified. Further, a total of 34 individual palms that collectively captured
maximum allelic diversity with reduced redundancy were also identified. High
pairwise genetic differentiation (Fst > 0.250) among populations was evident,
particularly between the Colombian populations and those from Honduras, Panama
and Costa Rica. Crossing selected palms from highly differentiated populations
could generate off-springs that retain more genetic diversity. CONCLUSION: The
results attained are useful for selecting palms and populations for core
collection. The selected materials can also be included into crossing scheme to
generate offsprings that capture greater genetic diversity for selection gain in
the future.
PMID- 28420333
TI - Strategies and cost-effectiveness evaluation of persistent albuminuria screening
among high-risk population of chronic kidney disease.
AB - BACKGROUND: Screening for persistent albuminuria among the high-risk population
is important for early detection of CKD while studies regarding screening
protocol and related cost-effectiveness analysis are limited. This study explored
a feasible and cost-efficient screening strategy for detecting persistent
albuminuria among the high-risk population. METHODS: A cohort study including 157
clinically stable outpatients with a risk factor of CKD and whose laboratory
tests revealed an albumin-creatinine-ratio (ACR) between 30 and 300 mg/g of
creatinine during the previous 12 months was conducted to assess the validity of
alternative screening strategies. Each participant collected three first morning
urine samples in three consecutive months. These samples were labeled as DAY-1,
MONTH-2 and MONTH-3. In the first month, a random spot sample in the afternoon of
the first day and another morning sample on the second day were collected and
labeled as Random and DAY-2. Persistent albuminuria was defined by abnormal ACR
(>=30 mg/g creatinine) for DAY-1, MONTH-2 and MONTH-3. Alternative strategies
were DAY-1; Random; DAY-1 + Random; DAY-1 + DAY-2; and DAY-1 + Random + DAY-2. To
evaluate the economic performance of those alternative strategies, a hybrid
decision tree/Markov model was developed based on the cohort study to simulate
both clinical and cost-effectiveness outcomes. Sensitivity analyses were
conducted to investigate assumptions of the model and to examine the model's
robustness. RESULTS: Altogether, 82 patients exhibited persistent albuminuria.
All of the five strategies had sensitivity higher than 90%. Of these strategies,
Random had the lowest specificity (46.7%), and DAY-1 + Random + DAY-2 had the
highest specificity (81.3%). Estimated cost for each quality adjusted life year
(QALYs) gained were Y112,335.88 for DAY-1 + Random, Y8134.69 for Random and
Y10,327.99 for DAY-1 + Random + DAY-2. When compared with DAY-1 strategy, the
sensitivity and specificity of which were 100.0 and 69.3%, respectively. DAY-1 +
Random + DAY-2 had the highest effectiveness and incremental effectiveness of
11.87 and 0.73 QALYs. At a willingness-to-pay threshold of Y100,000 per QALY, DAY
1 + Random + DAY-2 had the highest acceptability of 91.0%. Sensitivity analyses
demonstrated the robustness of the results. CONCLUSIONS: In order to make a quick
diagnosis of persistent albuminuria among high-risk population, the strategy of
combining two first morning urine samples and one randomized spot urine sample in
two consecutive days is accurate, saves time, and is cost-effective.
PMID- 28420334
TI - Mucormycosis in renal transplant recipients: review of 174 reported cases.
AB - BACKGROUND: Mucormycosis is a highly lethal fungal infection especially in
immunocompromised individuals. METHODS: In order to review the epidemiology,
diagnosis, and treatment of mucormycosis in renal transplant recipients we
searched publications of mucormycosis cases in renal transplant recipients in
PUBMED database up to December 2015. RESULTS: A total of 174 cases in renal
transplant recipients were included in this review. Most of the cases (76%) were
male. Major underlying diseases were diabetes mellitus (43.1%). Rhinocerebral was
the most common site of infection (33.3%). Rhizopus species was the most frequent
fungus (59.1%) in patients with pathogen identified to species level. The
mortality rates of disseminated mucormycosis (76.0%) and graft renal (55.6%) were
higher than infection in other sites. The overall survival in patients received
surgical debridement combined with amphotericin B/posaconazole (70.2%) was higher
than those who received antifungal therapy alone (32.4%), surgery alone (36.4%)
or without therapy (0%) (p < 0.001). The overall survivals in patients receiving
posaconazole and lipid amphoterincin B were higher than that receiving
deoxycholate formulation (92.3% and 73.4% vs 47.4%). CONCLUSIONS: Mucormycosis is
a severe infection in renal transplant recipients. Surgical debridement combined
with antifungals, especially liposomal amphotericin B and posaconazole, can
significantly improve patient's overall survival.
PMID- 28420335
TI - Trajectories of Life Satisfaction and their Predictors among Korean Older Adults.
AB - BACKGROUND: Among older adults, life satisfaction (LS) correlates with health,
mortality, and successful ageing. As various potential threats to LS tend to
increase with advancing years, patterns of age-related changes in LS among older
adults remain inconsistent. This study aimed to identify LS trajectories in older
adults and the characteristics of individuals who experience them. METHODS: Large
scale, nationally representative, longitudinal data collected from 2005 to 2013
were analyzed for this study. The outcome measure was a summary of
multidimensional domains influencing LS: health, finance, housing, neighbor
relationships, and family relationships. Latent class growth models and logistic
regression models were used to identify trajectory groups and their predictors,
respectively. RESULTS: Within 3517 individuals aged 65 or older, five
trajectories were identified across eight follow-up years: "low-stable" (TG1; n =
282; 8%), "middle-stable" (TG2; n = 1146; 32.6%), "improving" (TG3; n = 75;
2.1%), "upper middle-stable" (TG4; n = 1653; 47%), and "high" (TG5; n = 361;
10.3%). High trajectory individuals more frequently had higher education,
financial security, good physical health, and good mental health than those in
the stable, but less satisfied, groups. Similarly, compared to the largest group
(upper middle-stable trajectory), individuals in the low-stable or middle-stable
trajectory group not only had poorer physical and mental health but were more
likely to be living alone, financially stressed, and residing in urban locations.
Individuals with improving trajectory were younger and in poorer mental health at
baseline compared to the upper middle-stable trajectory group. CONCLUSION: Life
satisfaction in the older follows distinct trajectories. For older adults,
trajectories are stable over time and predictable, in part, from individual
characteristics. Knowledge of these patterns is important for effective policy
and program development.
PMID- 28420336
TI - Reduced changes in protein compared to mRNA levels across non-proliferating
tissues.
AB - BACKGROUND: The quantitative relations between RNA and protein are fundamental to
biology and are still not fully understood. Across taxa, it was demonstrated that
the protein-to-mRNA ratio in steady state varies in a direction that lessens the
change in protein levels as a result of changes in the transcript abundance.
Evidence for this behavior in tissues is sparse. We tested this phenomenon in new
data that we produced for the mouse auditory system, and in previously published
tissue datasets. A joint analysis of the transcriptome and proteome was performed
across four datasets: inner-ear mouse tissues, mouse organ tissues,
lymphoblastoid primate samples and human cancer cell lines. RESULTS: We show that
the protein levels are more conserved than the mRNA levels in all datasets, and
that changes in transcription are associated with translational changes that
exert opposite effects on the final protein level, in all tissues except cancer.
Finally, we observe that some functions are enriched in the inner ear on the mRNA
level but not in protein. CONCLUSIONS: We suggest that partial buffering between
transcription and translation ensures that proteins can be made rapidly in
response to a stimulus. Accounting for the buffering can improve the prediction
of protein levels from mRNA levels.
PMID- 28420337
TI - Right aortic arch analysis - Anatomical variant or serious vascular defect?
AB - BACKGROUND: The right-sided aortic arch (RAA) is a rare congenital defect of the
aorta. The aim of the study was to assess the occurrence of RAA in diagnoses
performed by the University Radiology Department and analyze the frequency of
concomitant vascular abnormalities. METHODS: The database of the Radiology
Department was retrospectively analyzed between January 2008 and May 2016 with
the keyword "right aortic arch". Twenty patients with this diagnosis were
identified from a total of 11,690 CT examinations of the chest area, 19,623 CT
examinations of brain-supplying vessels, and 1863 MRI examinations of the heart
and aortic arch or brain-supplying arteries. The type of aortic arch, the
occurrence of Kommerell's diverticulum and possible other vascular abnormalities,
such as stenosis, kinking or occlusion, were then investigated. RESULTS: The
analysis identified nine patients with type I and 11 patients with type II RAA.
Eight of the 11 type II patients presented Kommerell's diverticulum. Concomitant
vascular abnormalities were detected in four patients with type II RAA. In two
cases, the right common carotid artery (RCCA) was narrowed by up to 80%, with
steal phenomenon confirmed in one of them. In the second coincident right
subclavian artery (RSA) stenosis was depicted. In two other cases, the aberrant
left subclavian arteries (ALSA) were found to be narrowed at the level of origin
by up to 70%. One patient was found with type B aortic dissection including ALSA
and Kommerell's diverticulum. CONCLUSIONS: Our observations indicate that
concomitant vascular abnormalities may occur more often than reported in
literature. Patients diagnosed with type II RAA should be examined with Doppler
ultrasonography to identify coincident vascular disorders, especially stenosis of
the common carotid arteries or subclavian arteries.
PMID- 28420338
TI - Review and evaluation of performance measures for survival prediction models in
external validation settings.
AB - BACKGROUND: When developing a prediction model for survival data it is essential
to validate its performance in external validation settings using appropriate
performance measures. Although a number of such measures have been proposed,
there is only limited guidance regarding their use in the context of model
validation. This paper reviewed and evaluated a wide range of performance
measures to provide some guidelines for their use in practice. METHODS: An
extensive simulation study based on two clinical datasets was conducted to
investigate the performance of the measures in external validation settings.
Measures were selected from categories that assess the overall performance,
discrimination and calibration of a survival prediction model. Some of these have
been modified to allow their use with validation data, and a case study is
provided to describe how these measures can be estimated in practice. The
measures were evaluated with respect to their robustness to censoring and ease of
interpretation. All measures are implemented, or are straightforward to
implement, in statistical software. RESULTS: Most of the performance measures
were reasonably robust to moderate levels of censoring. One exception was
Harrell's concordance measure which tended to increase as censoring increased.
CONCLUSIONS: We recommend that Uno's concordance measure is used to quantify
concordance when there are moderate levels of censoring. Alternatively, Gonen and
Heller's measure could be considered, especially if censoring is very high, but
we suggest that the prediction model is re-calibrated first. We also recommend
that Royston's D is routinely reported to assess discrimination since it has an
appealing interpretation. The calibration slope is useful for both internal and
external validation settings and recommended to report routinely. Our
recommendation would be to use any of the predictive accuracy measures and
provide the corresponding predictive accuracy curves. In addition, we recommend
to investigate the characteristics of the validation data such as the level of
censoring and the distribution of the prognostic index derived in the validation
setting before choosing the performance measures.
PMID- 28420339
TI - Protocol for the development of a salutogenic intrapartum core outcome set
(SIPCOS).
AB - BACKGROUND: Maternity intrapartum care research and clinical care more often
focus on outcomes that minimise or prevent adverse health rather than on what
constitutes positive health and wellbeing (salutogenesis). This was highlighted
recently in a systematic review of reviews of intrapartum reported outcomes where
only 8% of 1648 individual outcomes, from 102 systematic reviews, were agreed as
being salutogenically-focused. Added to this is variation in the outcomes
measured in individual studies rendering it very difficult for researchers to
synthesise, fully, the evidence from studies on a particular topic. One of the
suggested ways to address this is to develop and apply an agreed standardised set
of outcomes, known as a 'core outcome set' (COS). In this paper we present a
protocol for the development of a salutogenic intrapartum COS (SIPCOS) for use in
maternity care research and a SIPCOS for measuring in daily intrapartum clinical
care. METHODS: The study proposes three phases in developing the final SIPCOSs.
Phase one, which is complete, involved the conduct of a systematic review of
reviews to identify a preliminary list of salutogenically-focused outcomes that
had previously been reported in systematic reviews of intrapartum interventions.
Sixteen unique salutogenically-focused outcome categories were identified. Phase
two will involve prioritising these outcomes, from the perspective of key
stakeholders (users of maternity services, clinicians and researchers) by asking
them to rate the importance of each outcome for inclusion in the SIPCOSs. A final
consensus meeting (phase three) will be held, bringing international stakeholders
together to review the preliminary SIPCOSs resulting from the survey and to agree
and finalise the final SIPCOSs for use in future maternity care research and
daily clinical care. DISCUSSION: The expectation in developing the SIPCOSs is
that they will be collected and reported in all future studies evaluating
intrapartum interventions and measured/recorded in future intrapartum clinical
care, as routine, alongside other outcomes also deemed important in the context
of the study or clinical scenario. Using the SIPCOSs in this way, will promote
and encourage standardised measurements of positive health outcomes in maternity
care, into the future.
PMID- 28420340
TI - Genetics and mapping of a new anthracnose resistance locus in Andean common bean
Paloma.
AB - BACKGROUND: The Andean cultivar Paloma is resistant to Mesoamerican and Andean
races of Colletotrichum lindemuthianum, the fungal pathogen that causes the
destructive anthracnose disease in common bean. Remarkably, Paloma is resistant
to Mesoamerican races 2047 and 3481, which are among the most virulent races of
the anthracnose pathogen. Most genes conferring anthracnose resistance in common
bean are overcome by these races. The genetic mapping and the relationship
between the resistant Co-Pa gene of Paloma and previously characterized
anthracnose resistance genes can be a great contribution for breeding programs.
RESULTS: The inheritance of resistance studies for Paloma was performed in F2
population from the cross Paloma (resistant) * Cornell 49-242 (susceptible)
inoculated with race 2047, and in F2 and F2:3 generations from the cross Paloma
(resistant) * PI 207262 (susceptible) inoculated with race 3481. The results of
these studies demonstrated that a single dominant gene confers the resistance in
Paloma. Allelism tests performed with multiple races of C. lindemuthianum showed
that the resistance gene in Paloma, provisionally named Co-Pa, is independent
from the anthracnose resistance genes Co-1, Co-2, Co-3, Co-4, Co-5, Co-6, Co-12,
Co-13, Co-14, Co-15 and Co-16. Bulk segregant analysis using the SNP chip
BARCBean6K_3 positioned the approximate location of Co-Pa in the lower arm of
chromosome Pv01. Further mapping analysis located the Co-Pa gene at a 390 kb
region of Pv01 flanked by SNP markers SS82 and SS83 at a distance of 1.3 and 2.1
cM, respectively. CONCLUSIONS: The results presented here showed that Paloma
cultivar has a new dominant gene conferring resistance to anthracnose, which is
independent from those genes previously described. The linkage between the Co-Pa
gene and the SS82 and SS83 SNP markers will be extremely important for marker
assisted introgression of the gene into elite cultivars in order to enhance
resistance.
PMID- 28420341
TI - Genetic sequence-based prediction of long-range chromatin interactions suggests a
potential role of short tandem repeat sequences in genome organization.
AB - BACKGROUND: Knowing the three-dimensional (3D) structure of the chromatin is
important for obtaining a complete picture of the regulatory landscape. Changes
in the 3D structure have been implicated in diseases. While there exist
approaches that attempt to predict the long-range chromatin interactions, they
focus only on interactions between specific genomic regions - the promoters and
enhancers, neglecting other possibilities, for instance, the so-called structural
interactions involving intervening chromatin. RESULTS: We present a method that
can be trained on 5C data using the genetic sequence of the candidate loci to
predict potential genome-wide interaction partners of a particular locus of
interest. We have built locus-specific support vector machine (SVM)-based
predictors using the oligomer distance histograms (ODH) representation. The
method shows good performance with a mean test AUC (area under the receiver
operating characteristic (ROC) curve) of 0.7 or higher for various regions across
cell lines GM12878, K562 and HeLa-S3. In cases where any locus did not have
sufficient candidate interaction partners for model training, we employed
multitask learning to share knowledge between models of different loci. In this
scenario, across the three cell lines, the method attained an average performance
increase of 0.09 in the AUC. Performance evaluation of the models trained on 5C
data regarding prediction on an independent high-resolution Hi-C dataset (which
is a rather hard problem) shows 0.56 AUC, on average. Additionally, we have
developed new, intuitive visualization methods that enable interpretation of
sequence signals that contributed towards prediction of locus-specific
interaction partners. The analysis of these sequence signals suggests a potential
general role of short tandem repeat sequences in genome organization.
CONCLUSIONS: We demonstrated how our approach can 1) provide insights into
sequence features of locus-specific interaction partners, and 2) also identify
their cell-line specificity. That our models deem short tandem repeat sequences
as discriminative for prediction of potential interaction partners, suggests that
they could play a larger role in genome organization. Thus, our approach can (a)
be beneficial to broadly understand, at the sequence-level, chromatin
interactions and higher-order structures like (meta-) topologically associating
domains (TADs); (b) study regions omitted from existing prediction approaches
using various information sources (e.g., epigenetic information); and
PMID- 28420342
TI - Impact of correlation of predictors on discrimination of risk models in
development and external populations.
AB - BACKGROUND: The area under the ROC curve (AUC) of risk models is known to be
influenced by differences in case-mix and effect size of predictors. The impact
of heterogeneity in correlation among predictors has however been under
investigated. We sought to evaluate how correlation among predictors affects the
AUC in development and external populations. METHODS: We simulated hypothetical
populations using two different methods based on means, standard deviations, and
correlation of two continuous predictors. In the first approach, the distribution
and correlation of predictors were assumed for the total population. In the
second approach, these parameters were modeled conditional on disease status. In
both approaches, multivariable logistic regression models were fitted to predict
disease risk in individuals. Each risk model developed in a population was
validated in the remaining populations to investigate external validity. RESULTS:
For both approaches, we observed that the magnitude of the AUC in the development
and external populations depends on the correlation among predictors. Lower AUCs
were estimated in scenarios of both strong positive and negative correlation,
depending on the direction of predictor effects and the simulation method.
However, when adjusted effect sizes of predictors were specified in the opposite
directions, increasingly negative correlation consistently improved the AUC. AUCs
in external validation populations were higher or lower than in the derivation
cohort, even in the presence of similar predictor effects. CONCLUSIONS:
Discrimination of risk prediction models should be assessed in various external
populations with different correlation structures to make better inferences about
model generalizability.
PMID- 28420343
TI - On the association analysis of CNV data: a fast and robust family-based
association method.
AB - BACKGROUND: Copy number variation (CNV) is known to play an important role in the
genetics of complex diseases and several methods have been proposed to detect
association of CNV with phenotypes of interest. Statistical methods for CNV
association analysis can be categorized into two different strategies. First, the
copy number is estimated by maximum likelihood and association of the expected
copy number with the phenotype is tested. Second, the observed probe intensity
measurements can be directly used to detect association of CNV with the
phenotypes of interest. RESULTS: For each strategy we provide a statistic that
can be applied to extended families. The computational efficiency of the proposed
methods enables genome-wide association analysis and we show with simulation
studies that the proposed methods outperform other existing approaches. In
particular, we found that the first strategy is always more efficient than the
second strategy no matter whether copy numbers for each individual are well
identified or not. With the proposed methods, we performed genome-wide CNV
association analyses of hematological trait, hematocrit, on 521 Korean family
samples. CONCLUSIONS: We found that statistical analysis with the expected copy
number is more powerful than the statistic with the probe intensity measurements
regardless of the accuracy of the estimation of copy numbers.
PMID- 28420344
TI - Erratum to: The JBEI quantitative metabolic modeling library (jQMM): a python
library for modeling microbial metabolism.
PMID- 28420345
TI - Selective sweep with significant positive selection serves as the driving force
for the differentiation of japonica and indica rice cultivars.
AB - BACKGROUND: Asian cultivated rice (Oryza sativa L.), including japonica and
indica, is unarguable the most important crop in Asia as well as worldwide.
However, a decisive conclusion of its origination and domestication processes are
still lacking. Nowadays, the ever-increasing high-throughput sequencing data of
numerous rice samples have provided us new opportunities to get close to the
answer of these questions. RESULTS: By compiling 296 whole-genome sequenced rice
cultivars and 39 diverse wild rice, two types of domesticated regions (DR-I and
DR-II) with strong selective sweep signals between different groups were
detected. DR-I regions included 28 blocks which significantly differentiated
between japonica and indica subspecies, while DR-II regions were consisted of
another 28 blocks which significantly differentiated between wild and cultivated
rice, each covered 890 kb and 640 kb, respectively. In-depth analysis suggested
that both DR-Is and DR-IIs could have originated from Indo-China Peninsula to
southern China, and DR-IIs might be introgressed from indica to japonica.
Functional bias with significant positive selection has also been detected in the
genes of DR-I, suggesting important role of the selective sweep in
differentiation of japonica and indica. CONCLUSIONS: This research promoted a new
possible model of the origin of the cultivated rice that DR-Is in japonica and
indica maybe independently originated from the divergent wild rice in the Indo
China Peninsula to southern China, and then followed by frequent introgression.
Genes with significant positive selection and biased functions were also detected
which could play important roles in rice domestication and differentiation
processes.
PMID- 28420347
TI - Kappa statistic to measure agreement beyond chance in free-response assessments.
AB - BACKGROUND: The usual kappa statistic requires that all observations be
enumerated. However, in free-response assessments, only positive (or abnormal)
findings are notified, but negative (or normal) findings are not. This situation
occurs frequently in imaging or other diagnostic studies. We propose here a kappa
statistic that is suitable for free-response assessments. METHOD: We derived the
equivalent of Cohen's kappa statistic for two raters under the assumption that
the number of possible findings for any given patient is very large, as well as a
formula for sampling variance that is applicable to independent observations (for
clustered observations, a bootstrap procedure is proposed). The proposed
statistic was applied to a real-life dataset, and compared with the common
practice of collapsing observations within a finite number of regions of
interest. RESULTS: The free-response kappa is computed from the total numbers of
discordant (b and c) and concordant positive (d) observations made in all
patients, as 2d/(b + c + 2d). In 84 full-body magnetic resonance imaging
procedures in children that were evaluated by 2 independent raters, the free
response kappa statistic was 0.820. Aggregation of results within regions of
interest resulted in overestimation of agreement beyond chance. CONCLUSIONS: The
free-response kappa provides an estimate of agreement beyond chance in situations
where only positive findings are reported by raters.
PMID- 28420346
TI - Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking
broken symmetries in molecular biology, mood disorders and personalistic
emergentism.
AB - In this paper we present a mechanistic model that integrates subneuronal
structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins
and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain.
We also argue that subtle changes in the composition of the membrane's fatty
acids may lead to down-stream effects causing dysregulation of the membrane,
cytoskeleton and their interface. Such exquisite sensitivity to minor changes is
known to occur in physical systems undergoing phase transitions, the simplest and
most studied of them is the so-called Ising model, which exhibits a phase
transition at a finite temperature between an ordered and disordered state in 2-
or 3-dimensional space. We propose this model in the context of neuronal dynamics
and further hypothesize that it may involve quantum degrees of freedom dependent
upon variation in membrane domains associated with ion channels or microtubules.
Finally, we provide a link between these physical characteristics of the
dynamical mechanism to psychiatric disorders such as major depression and
antidepressant action.
PMID- 28420348
TI - Lower incidence of contrast-induced nephropathy in patients undergoing
fluorescent angiography.
AB - BACKGROUND: To evaluate the incidence and risk factors of contrast-induced
nephropathy (CIN) in patients undergoing fluorescein angiography (FA). METHODS:
One hundred sixty patients who underwent FA as a part of ophthalmic examination
and had serum creatinine (SCr) results within 24 h before FA and within 72 h
after FA between 2005 and 2013 at a tertiary medical center were included.
According to baseline SCr levels, the subjects were divided into low-risk group
(<1.5 mg/dL), intermediate-risk group (1.5-2.0 mg/dL), and high-risk group (>2.0
mg/dL) for CIN development. The CIN incidence, and changes in renal function
defined by SCr levels and estimated glomerular filtration rate (eGFR) were
evaluated. Demographics and comorbidities were analyzed to investigate an
association with CIN development. RESULTS: Of 160 patients, 91 were males
(56.9%). The mean age was 52.46 +/- 17.81 years. Two (1.3%) patients developed
CIN after FA, whose SCr levels returned to normal within 10 days without
hemodialysis. Overall, there were no changes before and after FA in SCr level
(1.52 +/- 1.31 mg/dL vs. 1.51 +/- 1.28 mg/dL, respectively; p = 0.93) and eGFR
(67.02 +/- 36.62 mL/min/1.73 m2 vs. 66.41 +/- 36.54 mL/min/1.73 m2, respectively;
p = 0.54). SCr level and eGFR remained unchanged after FA in low-risk and
intermediate-risk groups. In high-risk group, eGFR remined unchanged, but SCr
level decreased after FA (from 3.64 +/- 1.59 mg/dL to 3.53 +/- 1.60 mg/dL; p =
0.04). Basline SCr and cormorbidities did not predict CIN development.
CONCLUSIONS: Acute renal function deterioration was not evident in patients
undergoing FA regardless of baseline renal function and comorbidities.
PMID- 28420349
TI - Grey literature in systematic reviews: a cross-sectional study of the
contribution of non-English reports, unpublished studies and dissertations to the
results of meta-analyses in child-relevant reviews.
AB - BACKGROUND: Systematic reviews (SRs) are an important source of information about
healthcare interventions. A key component of a well-conducted SR is a
comprehensive literature search. There is limited evidence on the contribution of
non-English reports, unpublished studies, and dissertations and their impact on
results of meta-analyses. METHODS: Our sample included SRs from three Cochrane
Review Groups: Acute Respiratory Infections (ARI), Infectious Diseases (ID),
Developmental Psychosocial and Learning Problems (DPLP) (n = 129). Outcomes
included: 1) proportion of reviews that searched for and included each study
type; 2) proportion of relevant studies represented by each study type; and 3)
impact on results and conclusions of the primary meta-analysis for each study
type. RESULTS: Most SRs searched for non-English studies; however, these were
included in only 12% of reviews and represented less than 5% of included studies.
There was a change in results in only four reviews (total sample = 129); in two
cases the change did not have an impact on the statistical or clinical
significance of results. Most SRs searched for unpublished studies but the
majority did not include these (only 6%) and they represented 2% of included
studies. In most cases the impact of including unpublished studies was small; a
substantial impact was observed in one case that relied solely on unpublished
data. Few reviews in ARI (9%) and ID (3%) searched for dissertations compared to
65% in DPLP. Overall, dissertations were included in only nine SRs and
represented less than 2% of included studies. In the majority of cases the change
in results was negligible or small; in the case where a large change was noted,
the estimate was more conservative without dissertations. CONCLUSIONS: The
majority of SRs searched for non-English and unpublished studies; however, these
represented a small proportion of included studies and rarely impacted the
results and conclusions of the review. Inclusion of these study types may have an
impact in situations where there are few relevant studies, or where there are
questionable vested interests in the published literature. We found substantial
variation in whether SRs searched for dissertations; in most reviews that
included dissertations, these had little impact on results.
PMID- 28420350
TI - Trends in baseline CD4 cell counts and risk factors for late antiretroviral
therapy initiation among HIV-positive patients in Shanghai, a retrospective cross
sectional study.
AB - BACKGROUNDS: There are few studies focus on the factors underlying the late
initiation of ART in China. We analyzed the trends in the median CD4 cell counts
among different patient groups over time and the risk factors for the late
initiation of ART in Shanghai, China. METHODS: A retrospective cross-sectional
survey was made in the Department of Infectious Disease of Shanghai Public Health
Clinical Center which is a designated diagnosis and treatment center for HIV
positive patients in Shanghai during the period of January 1st, 2008--June 30th,
2014. Late ART initiation was defined as a CD4 cell count <200 cells/mm3 or
having a clinical AIDS diagnosis prior to ART initiation. Trends in the median
CD4 cell count at ART initiation and the proportion of late ART initiation by
year were evaluated using Spearman's correlations and Chi-squared methods,
respectively. We used a logistic regression model to analyze the risk factors for
late ART initiation. The related factors collected in the multivariate model were
the patient's age, gender, infection routes and marital status. RESULTS: A total
of 3796 patients were analyzed in this study, with a median baseline CD4 cell
count of 205 cells/mm3 [interquartile range: 75-287]. The median CD4 cell counts
of patients initiating ART late increased from 76 cells/mm3 in 2008 to 103
cells/mm3 in 2014 (p < 0.001), and the proportion of late ART initiation
decreased from 80% to 45% (p < 0.001). The risk factors for late ART initiation
were male gender, heterosexual transmission and older age (>30 years) (p <
0.001). CONCLUSIONS: Notable improvements were made in the median CD4 cell count
at ART initiation and the proportion of late ART initiation from 2008 to 2014.
However, persons with high risk of HIV exposure who are male, older even
heterosexual orientation should be given more opportunities to receive frequently
screening, earlier diagnoses and timely treatment.
PMID- 28420351
TI - Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial
cells of patients with early breast cancer.
AB - BACKGROUND: Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not
associated with the vasculature, of patients with early breast cancer express
osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell
derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine
(C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels
compared with non-neoplastic breast tissues. We evaluated the clinicopathological
significance of these ligands and receptors in TEpC and spindle-shaped stromal
cells, not associated with the vasculature, to determine their impact on
prognosis of patients with early-stage breast cancer. METHODS: We conducted
immunohistochemical analyses of protein expression in primary tumors of patients
with early breast cancer and analyzed their association with standard prognostic
parameters and clinical outcomes, including local relapse, metastatic recurrence,
disease-free survival (DFS), metastasis-free survival (MFS), and overall survival
(OS). RESULTS: Elevated levels of TRAIL-R3 and chemokine (C-C motif) receptor 2
(CCR-2) in TEpCs and OPG and CCL-2 in stromal cells were significantly associated
with a higher risk of metastasis (p = 0.032, p = 0.003, p = 0.038, and p = 0.049;
respectively). Moreover, high expression of TRAIL-R3 and CCR-2 in TEpCs was
associated with shorter DFS, MFS, and OS. High TRAIL-R3 expression in TEpCs was
an independent prognostic factor for DFS and OS, and high CCR-2 expression in
these cells was an independent prognostic factor for MFS. CONCLUSIONS: High
levels of TRAIL-R3 and CCR-2 expression in TEpCs identified patients with early
breast cancer with poor outcomes.
PMID- 28420352
TI - Assessing the reliability of self-reported weight for the management of heart
failure: application of fraud detection methods to a randomised trial of
telemonitoring.
AB - BACKGROUND: Since clinical management of heart failure relies on weights that are
self-reported by the patient, errors in reporting will negatively impact the
ability of health care professionals to offer timely and effective preventive
care. Errors might often result from rounding, or more generally from individual
preferences for numbers ending in certain digits, such as 0 or 5. We apply fraud
detection methods to assess preferences for numbers ending in these digits in
order to inform medical decision making. METHODS: The Telemonitoring to Improve
Heart Failure Outcomes trial tested an approach to telemonitoring that used
existing technology; intervention patients (n = 826) were asked to measure their
weight daily using a digital scale and to relay measurements using their
telephone keypads. First, we estimated the number of weights subject to end-digit
preference by dividing the weights by five and comparing the resultant
distribution with the uniform distribution. Then, we assessed the characteristics
of patients reporting an excess number of weights ending in 0 or 5, adjusting for
chance reporting of these values. RESULTS: Of the 114,867 weight readings
reported during the trial, 18.6% were affected by end-digit preference, and the
likelihood of these errors occurring increased with the number of days that had
elapsed since trial enrolment (odds ratio per day: 1.002, p < 0.001). At least
105 patients demonstrated end-digit preference (14.9% of those who submitted
data); although statistical significance was limited, a pattern emerged that,
compared with other patients, they tended to be younger, male, high school
graduates and on more medications. Patients with end-digit preference reported
greater variability in weight, and they generated an average 2.9 alerts to the
telemonitoring system over the six-month trial period (95% CI, 2.3 to 3.5),
compared with 2.3 for other patients (95% CI, 2.2 to 2.5). CONCLUSIONS: As well
as overshadowing clinically meaningful changes in weight, end-digit preference
can lead to false alerts to telemonitoring systems, which may be associated with
unnecessary treatment and alert fatigue. In this trial, end-digit preference was
common and became increasingly so over time. By applying fraud detection methods
to electronic medical data, it is possible to produce clinically significant
information that can inform the design of initiatives to improve the accuracy of
reporting. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT00303212
March 2006.
PMID- 28420353
TI - The influence of fatigue and chronic low back pain on muscle recruitment patterns
following an unexpected external perturbation.
AB - BACKGROUND: Chronic low back pain (CLBP) has been associated with altered trunk
muscle responses as well as increased muscle fatigability. CLBP patients and
fatigued healthy subjects could experience similar neuromuscular strategies to
attempt to protect the spine. The current study examined muscle activation
differences between healthy and CLBP subjects following a perturbation. In
addition, the possible role of muscle fatigue was evaluated by investigating the
healthy control subjects in a non-fatigued and a fatigued condition. Both
experiments were combined to evaluate possible similar strategies between CLBP
and fatigued samples. METHODS: Cross-sectional study where 24 CLBP subjects and
26 healthy subjects were evaluated. Both groups (CLBP vs. healthy) and both
conditions (non-fatigued and a fatigued condition) were evaluated while a weight
was suddenly dropped on a held tray. Erector spinae, multifidus, obliques and
biceps brachii were recorded using surface electromyography. Variables describing
the bursts timing and variables describing the amount of muscle activity (number
of bursts and amplitude increase) post impact were studied. The analysis between
groups and conditions was carried out using ANOVAs with repeated measurements for
the muscle factor. RESULTS: CLBP subjects reacted similarly to healthy subjects
regarding muscle activity post impact. However, the CLBP group showed temporal
characteristics of muscle activity that were in between the fatigued and non
fatigued healthy group. Clear differences in muscle activity were displayed for
healthy subjects. Fatigued healthy subjects presented more reduced activity after
impact (upper limb and trunk muscles) than non-fatigued healthy subjects and
different temporal characteristic in the same way than CLBP patients. This same
temporal characteristic with CLBP and healthy fatigued people was a delay of the
first burst of muscle activity after impact. CONCLUSION: Though similar muscle
pattern existed between CLBP and healthy people, CLBP temporal characteristics of
muscle activity showed a pattern in between healthy people and fatigued healthy
people. While the temporal muscle pattern dysfunction used by CLBP subjects could
be related to maladaptive patterns, temporal and muscle activity characteristics
used by healthy fatigued people may lead to back injuries.
PMID- 28420354
TI - Therapeutic potentials of Crataegus azarolus var. eu- azarolus Maire leaves and
its isolated compounds.
AB - BACKGROUND: Hyperglycemia is a complicated condition accompanied with high
incidence of infection and dyslipidemia. This study aimed to explore the phyto
constituents of Crataegus azarolus var. eu- azarolus Maire leaves, and to
evaluate the therapeutic potentials particularly antimicrobial, antihyperglycemic
and antihyperlipidemic of the extract and the isolated compound (3beta-O-acetyl
ursolic acid). METHODS: Total phenolics and flavonoidal contents were measured by
RP-HPLC analysis. Free radicals scavenging activity of different extraction
solvents was tested in-vitro on DPPH free radicals. The antimicrobial activity of
the ethanolic extract and its fractions as well as the isolated compounds were
evaluated in-vitro on variable microorganisms. Animal models were used to
evaluate the antihyperglycemic and antihyperlipidemic activities of the ethanolic
extract along with the isolated compound (3beta-O acetyl ursolic acid). RESULTS:
RP- HPLC analysis of the phenolics revealed high content of rutin, salicylic and
ellagic acids. Six compounds belonging to triterpenes and phenolics were isolated
from chloroform and n-butanol fractions namely: ursolic acid, 3beta-O-acetyl
ursolic acid, ellagic acid, quercetin 3-O-beta methyl ether, rutin and apigenin7
O-rutinoside. Ethanolic extract showed the highest DPPH radical scavenger
activity compared to other solvents. Ethanolic extract, hexane fraction, ursolic
acid, 3beta-O acetyl ursolic acid and quercetin 3-O-methyl ether showed variable
antimicrobial activity against E. coli, P. aeruginosa, S. aureus, and C.
albicans. Administration of the ethanolic extract or 3beta-O acetyl ursolic acid
orally to the mice reduced blood glucose significantly in a time- and dose
dependent manner. Ethanolic extract significantly reduced LDL-C, VLDL-C, TC and
TG and increased HDL-C in rats. Ethanolic extract and 3beta-O acetyl ursolic acid
reduced in-vitro activity of pancreatic lipase. CONCLUSION: This study reveals
that Crataegus azarolus var. eu- azarolus Maire has the efficiency to control
hyperglycemia with its associated complications. This study is the first to
evaluate antihyperglycemic and antihyperlipidemic potentials of 3beta-O acetyl
ursolic acid.
PMID- 28420355
TI - Facilitators and barriers to using physical activity smartphone apps among
Chinese patients with chronic diseases.
AB - BACKGROUND: Smartphones and their applications (apps) impact society and health
care. With the growth of smartphone users and app downloads in China, patients
with chronic diseases have access to a self-management strategy for physical
activity. Although studies report physical activity apps improve the physical
activity of patients, data is limited concerning their use of these apps.
Therefore, this study investigated the current usage, willingness to use, and
barriers to using physical activity apps of Chinese patients with chronic
diseases. METHODS: We designed a questionnaire to collect data from chronic
disease patients in a tertiary hospital in Beijing, which was sent to 250
patients in four departments. RESULTS: Two hundred eighteen questionnaires were
returned (87.2% response rate). Most (92.7%) respondents owned a smartphone,
34.9% had used a physical activity app, and 18.8% were current users.
Additionally, 53.7% were willing to use a physical activity app designed for
them. Respondents more likely to use physical activity apps were younger (i.e.,
<= 44 years), more educated, current smartphone users, and previous users of
physical activity apps; moreover, they believed they needed exercise, their
disease required exercise instruction and support, and their physical status
needed monitored when exercising (p < 0.05). Main barriers to using apps reported
were insufficient function, difficulty of use, extra cost, and security issues.
CONCLUSIONS: Our results indicate sizeable smartphone ownership among Chinese
patients with chronic diseases; moreover, over half of our participants report
they would use a physical activity app designed for them. This information can be
leveraged by healthcare workers managing patients with chronic diseases.
PMID- 28420356
TI - An assessment of the HIV/TB knowledge and skills of home-based carers working in
the North West province in South Africa: a cross-sectional study.
AB - BACKGROUND: Home-based carers (HBCs) play a critical role in ensuring the success
of the primary health care re-engineering strategy in South Africa. Their role
includes ensuring improved access to and delivery of primary health care at the
household level, and better co-ordination and improved linkages between community
and health facilities for HIV/TB services. The objective of this study was to
assess the knowledge, skills, challenges and training needs of HBCs involved in
HIV/TB care in one sub-district in the North-West province of South Africa.
METHODS: We conducted a descriptive, cross-sectional study in which 157 HBCs were
interviewed to assess their knowledge and skills regarding HIV and TB. Data were
collected using a pre-tested semi-structured questionnaire. Quantitative and
qualitative data were analysed using SPSS statistical software and thematic
analysis respectively. RESULTS: One hundred and forty-four (92%) of the
interviewees were female and 13 (8%) were male. The median age of the
participants was 35 years (interquartile range (IQR): 22-27). The median score
for knowledge of both HIV and TB questions was 66% (IQR: 57-75). In general, HIV
knowledge scores were higher than TB knowledge scores (73% versus 66%). A
significant association was found between knowledge scores and formal training (p
< 0.05), and knowledge scores and highest educational levels (p < 0.05).
Irrespective of knowledge, HBCs reported providing a variety of services to
support HIV/TB services in the communities in which they worked. HBCs also
reported facing various challenges in their jobs related to stigma and the social
contexts in which they work. CONCLUSION: The study showed that the overall
knowledge of HBCs was limited, given the skills required and the services they
provide. Given the increasing role of HBCs in various health initiatives,
targeted interventions are required to support and improve their competencies and
service provision.
PMID- 28420357
TI - In search of quality indicators for Down syndrome healthcare: a scoping review.
AB - BACKGROUND: The medical care chain around Down syndrome (DS) is complex, with
many multidisciplinary challenges. The current quality of care is unknown.
Outcome-oriented quality indicators have the potential to improve medical
practice and evaluate whether innovations are successful. This is particularly
interesting for the evolving care for people with DS and intellectual
disabilities (ID). The aim of this study was to identify existing indicators for
medical DS care, by reviewing the literature. METHODS: We systematically searched
six databases (PubMed, EMBASE, Web of Science, CINAHL, PsycINFO, Google Scholar)
for studies concerning the development and implementation of quality indicators
for DS and/or ID care, published until February 1st 2015. The scoping review
method was used, including systematic data extraction and stakeholder
consultation. RESULTS: We identified 13 studies concerning quality indicators for
ID care that obtained data originating from questionnaires
(patient/family/staff), medical files and/or national databases. We did not find
any indicator sets specifically for DS care. Consulted stakeholders did not come
up with additional indicator sets. Existing indicators for ID care predominantly
focus on support services. Indicators in care for people with ID targeting
medical care are scarce. Of the 70 indicators within the 13 indicator sets, 10%
are structure indicators, 34% process, 32% outcome and 24% mixed. Ten of the 13
sets include indicators on the WHO quality dimensions 'patient-centeredness',
'effectiveness' and 'efficiency' of care. 'Accessibility' is covered by nine
sets, 'equitability' by six, and 'safety' by four. Most studies developed
indicators in a multidisciplinary manner in a joint effort with all relevant
stakeholders; some used focus groups to include people with ID. CONCLUSION: To
our knowledge, this is the first review that searched for studies on quality
indicators in DS care. Hence, the study contributes to existing knowledge on DS
care as well as on measuring quality of care. Future research should address the
development of a compact set of quality indicators for the DS care chain as a
whole. Indicators should preferably be patient-centred and outcome-oriented,
including user perspectives, while developed in a multidisciplinary way to
achieve successful implementation.
PMID- 28420358
TI - Healthcare utilization in older patients using personal emergency response
systems: an analysis of electronic health records and medical alert data : Brief
Description: A Longitudinal Retrospective Analyses of healthcare utilization
rates in older patients using Personal Emergency Response Systems from 2011 to
2015.
AB - BACKGROUND: Personal Emergency Response Systems (PERS) are traditionally used as
fall alert systems for older adults, a population that contributes an
overwhelming proportion of healthcare costs in the United States. Previous
studies focused mainly on qualitative evaluations of PERS without a longitudinal
quantitative evaluation of healthcare utilization in users. To address this gap
and better understand the needs of older patients on PERS, we analyzed
longitudinal healthcare utilization trends in patients using PERS through the
home care management service of a large healthcare organization. METHODS:
Retrospective, longitudinal analyses of healthcare and PERS utilization records
of older patients over a 5-years period from 2011-2015. The primary outcome was
to characterize the healthcare utilization of PERS patients. This outcome was
assessed by 30-, 90-, and 180-day readmission rates, frequency of principal
admitting diagnoses, and prevalence of conditions leading to potentially
avoidable admissions based on Centers for Medicare and Medicaid Services
classification criteria. RESULTS: The overall 30-day readmission rate was 14.2%,
90-days readmission rate was 34.4%, and 180-days readmission rate was 42.2%.
While 30-day readmission rates did not increase significantly (p = 0.16) over the
study period, 90-days (p = 0.03) and 180-days (p = 0.04) readmission rates did
increase significantly. The top 5 most frequent principal diagnoses for inpatient
admissions included congestive heart failure (5.7%), chronic obstructive
pulmonary disease (4.6%), dysrhythmias (4.3%), septicemia (4.1%), and pneumonia
(4.1%). Additionally, 21% of all admissions were due to conditions leading to
potentially avoidable admissions in either institutional or non-institutional
settings (16% in institutional settings only). CONCLUSIONS: Chronic medical
conditions account for the majority of healthcare utilization in older patients
using PERS. Results suggest that PERS data combined with electronic medical
records data can provide useful insights that can be used to improve health
outcomes in older patients.
PMID- 28420359
TI - Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation
and oxidative stress: a proteomic study.
AB - BACKGROUND: Radix Bupleuri (RB) has been popularly used for treating many liver
diseases such as chronic hepatic inflammation and viral Hepatitis in China.
Increasing clinical and experimental evidence indicates the potential
hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS)
have been identified as major bioactive compounds isolated from RB, which may be
also responsible for RB-induced liver injury. METHODS: Serum AST, ALT and LDH
levels were determined to evaluate SS-induced liver injury in mice. Serum and
liver total triglyceride and cholesterol were used to indicate lipid metabolism
homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative
stress level after SS administration. Western blot was used to detect CYP2E1
expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was
applied to analyze the protein expression profiles in livers of mice administered
with different doses of SS for different time periods. Gene ontology analysis,
cluster and enrichment analysis were employed to elucidate potential mechanism
involved. HepG2 cells were used to identify our findings in vitro. RESULTS: SS
dose- and time-dependently induced liver injury in mice, indicated by increased
serum AST, ALT and LDH levels. According to proteomic analysis, 487
differentially expressed proteins were identified in mice administrated with
different dose of SS for different time periods. Altered proteins were enriched
in pathways such as lipid metabolism, protein metabolism, macro molecular
transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1
expression in a time and dose dependent manner, and induced oxidative stress both
in vivo and in vitro. CONCLUSION: Our results identified hepatotoxicity and
established dose-time course-liver toxicity relationship in mice model of SS
administration and suggested potential mechanisms, including impaired lipid and
protein metabolism and oxidative stress. The current study provides experimental
evidence for clinical safe use of RB, and also new insights into understanding
the mechanism by which SS and RB induced liver injury.
PMID- 28420360
TI - Operative versus conservative treatment of apophyseal avulsion fractures of the
pelvis in the adolescents: a systematical review with meta-analysis of clinical
outcome and return to sports.
AB - BACKGROUND: Avulsion fractures of the pelvic apophyses typically occur in
adolescent athletes due to a sudden strong muscle contraction while growth plates
are still open. The main goals of this systematic review with meta-analysis were
to summarize the evidence on clinical outcome and determine the rate of return to
sports after conservative versus operative treatment of avulsion fractures of the
pelvis. METHODS: A systematic search of the Ovid database was performed in
December 2016 to identify all published articles reporting outcome and return to
preinjury sport-level after conservative or operative treatment of avulsion
fractures of the pelvis in adolescent patients. Included studies were abstracted
regarding study characteristics, patient demographics and outcome measures. The
methodological quality of the studies was assessed with the Coleman Methodology
Score (CMS). RESULTS: Fourteen studies with a total of 596 patients met the
inclusion criteria. The mean patient age was 14.3 +/- 0.6 years and 75.5% of
patients were male. Affected were the anterior inferior iliac spine (33.2%),
ischial tuberosity (29.7%), anterior superior iliac spine (27.9%), iliac crest
(6.7%) lesser trochanter (1.8%) and superior corner of the pubic symphysis
(1.2%). Mean follow-up was 12.4 +/- 11.7 months and most of the patients
underwent a conservative treatment (89.6%). The overall success rate was higher
in the patients receiving surgery (88%) compared to the patients receiving
conservative treatment (79%) (p = 0,09). The rate of return to sports was 80% in
conservative and 92% in operative treated patients (p = 0,03). Overall, the
methodological quality of the included studies was low, with a mean CMS of 41.2.
CONCLUSION: On the basis of the present meta-analysis, the overall success and
return to sports rate was higher in the patients receiving surgery. Especially in
patients with fragment displacement greater 15 mm and high functional demands,
surgical treatment should be considered.
PMID- 28420361
TI - Health care availability, quality, and unmet need: a comparison of transgender
and cisgender residents of Ontario, Canada.
AB - BACKGROUND: Evidence suggests that transgender (trans) individuals in Canada are
a medically underserved population; barriers range from lack of provider
knowledge on trans issues to refusal of care. This paper provides the first
formal estimation of health care inequalities between trans and cisgender
individuals in Ontario, Canada. METHODS: Weighted statistics from the Ontario
wide Trans PULSE Project (n = 433) were compared with age-standardized Ontario
data from the Canadian Community Health Survey (n = 39,980) to produce
standardized prevalence differences (SPDs). Analysis was also conducted
separately for trans men and trans women, each compared to the age-standardized
Ontario population. RESULTS: An estimated 33.2% (26.4,40.9) of trans Ontarians
reported a past-year unmet health care need in excess of the 10.7% expected based
on the age-standardized Ontario population. Inequality was greatest comparing
trans with cisgender men (SPD = 34.4% (23.0, 46.1). While trans Ontarians
evaluated health care availability in Ontario similarly to the broader
population, they were significantly more likely to evaluate availability in their
community as fair or poor. CONCLUSIONS: Trans Ontarians experience inequalities
in perception and reported experiences of health care access, with 43.9%
reporting a past-year unmet health care need.
PMID- 28420362
TI - Clinical, hemispheric, and autonomic changes associated with use of closed-loop,
allostatic neurotechnology by a case series of individuals with self-reported
symptoms of post-traumatic stress.
AB - BACKGROUND: The objective of this pilot study was to explore the use of a closed
loop, allostatic, acoustic stimulation neurotechnology for individuals with self
reported symptoms of post-traumatic stress, as a potential means to impact
symptomatology, temporal lobe high frequency asymmetry, heart rate variability
(HRV), and baroreflex sensitivity (BRS). METHODS: From a cohort of individuals
participating in a naturalistic study to evaluate use of allostatic
neurotechnology for diverse clinical conditions, a subset was identified who
reported high scores on the Posttraumatic Stress Disorder Checklist (PCL). The
intervention entailed a series of sessions wherein brain electrical activity was
monitored noninvasively at high spectral resolutions, with software algorithms
translating selected brain frequencies into acoustic stimuli (audible tones) that
were delivered back to the user in real time, to support auto-calibration of
neural oscillations. Participants completed symptom inventories before and after
the intervention, and a subset underwent short-term blood pressure recordings for
HRV and BRS. Changes in temporal lobe high frequency asymmetry were analyzed from
baseline assessment through the first four sessions, and for the last four
sessions. RESULTS: Nineteen individuals (mean age 47, 11 women) were enrolled,
and the majority also reported symptom scores that exceeded inventory thresholds
for depression. They undertook a median of 16 sessions over 16.5 days, and 18
completed the number of sessions recommended. After the intervention, 89% of the
completers reported clinically significant decreases in post-traumatic stress
symptoms, indicated by a change of at least 10 points on the PCL. At a group
level, individuals with either rightward (n = 7) or leftward (n = 7) dominant
baseline asymmetry in temporal lobe high frequency (23-36 Hz) activity
demonstrated statistically significant reductions in their asymmetry scores over
the course of their first four sessions. For 12 individuals who underwent short
term blood pressure recordings, there were statistically significant increases in
HRV in the time domain and BRS (Sequence Up). There were no adverse events.
CONCLUSION: Closed-loop, allostatic neurotechnology for auto-calibration of
neural oscillations appears promising as an innovative therapeutic strategy for
individuals with symptoms of post-traumatic stress. TRIALS REGISTRATION:
ClinicalTrials.gov #NCT02709369 , retrospectively registered on March 4, 2016.
PMID- 28420363
TI - Context matters! sources of variability in weekend physical activity among
families: a repeated measures study.
AB - BACKGROUND: Family involvement is an essential component of effective physical
activity (PA) interventions in children. However, little is known about the PA
levels and characteristics of PA among families. This study used a repeated
measures design and multiple data sources to explore the variability and
characteristics of weekend PA among families. METHODS: Families (including a
'target' child aged 9-11 years, their primary caregiver(s) and siblings aged 6-8
years) were recruited through primary schools in Liverpool, UK. Participants
completed a paper-based PA diary and wore an ActiGraph GT9X accelerometer on
their left wrist for up to 16 weekend days. ActiGraph.csv files were analysed
using the R-package GGIR version 1.1-4. Mean minutes of moderate-to-vigorous PA
(MVPA) for each weekend of measurement were calculated using linear mixed models,
and variance components were estimated for participant (inter-individual),
weekend of measurement, and residual error (intra-individual). Intraclass
correlation coefficients (ICC) were calculated from the proportion of total
variance accounted for by inter-individual sources, and used as a measure of
reliability. Diary responses were summed to produce frequency counts. To offer
contextual insight into weekend PA among family units, demographic,
accelerometer, and diary data were combined to form two case studies
representative of low and high active families. RESULTS: Twenty-five participants
from 7 families participated, including 7 'target' children (mean age 9.3 +/- 1.1
years, 4 boys), 6 siblings (mean age 7.2 +/- 0.7 years; 4 boys) and 12 adults (7
mothers and 5 fathers). There was a high degree of variability in target
children's (ICC = 0.55), siblings (ICC = 0.38), and mothers' MVPA (ICC = 0.58),
but not in fathers' MVPA (ICC = 0.83). Children's weekend PA was mostly
unstructured in nature and undertaken with friends, whereas a greater proportion
of parents' weekend PA was undertaken alone in structured settings. The family
case studies demonstrated that in the selected cases MVPA levels and variability
across weekends were contingent on mode of PA participation. CONCLUSIONS: These
novel findings enhance understanding of the variability and characteristics of
weekend PA among family units. The study demonstrates the utility of PA diaries
in conjunction with accelerometers to provide understanding of the mode and
contexts of out-of-school and family-based PA.
PMID- 28420364
TI - Anterior inferior plating versus superior plating for clavicle fracture: a meta
analysis.
AB - BACKGROUND: The position of plate fixation for clavicle fracture remains
controversial. Our objective was to perform a comprehensive review of the
literature and quantify the surgical parameters and clinical indexes between the
anterior inferior plating and superior plating for clavicle fracture. METHODS:
PubMed, EMBASE, and the Cochrane Library were searched for randomized and non
randomized studies that compared the anterior inferior plating with the superior
plating for clavicle fracture. The relative risk or standardized mean difference
with 95% confidence interval was calculated using either a fixed- or random
effects model. RESULTS: Four randomized controlled trials and eight observational
studies were identified to compare the surgical parameters and clinical indexes.
For the surgical parameters, the anterior inferior plating group was better than
the superior plating group in operation time and blood loss (P < 0.05).
Furthermore, in terms of clinical indexes, the anterior inferior plating was
superior to the superior plating in reducing the union time, and the two kinds of
plate fixation methods were comparable in constant score, and the rate of
infection, nonunion, and complications (P > 0.05). CONCLUSIONS: Based on the
current evidence, the anterior inferior plating may reduce the blood loss, the
operation and union time, but no differences were observed in constant score, and
the rate of infection, nonunion, and complications between the two groups. Given
that some of the studies have low quality, more randomized controlled trails with
high quality should be conduct to further verify the findings.
PMID- 28420365
TI - Social determinants of antibiotic misuse: a qualitative study of community
members in Haryana, India.
AB - BACKGROUND: Antibiotic resistance is a global public health crisis. In India
alone, multi-drug resistant organisms are responsible for over 58,000 infant
deaths each year. A major driver of drug resistance is antibiotic misuse, which
is a pervasive phenomenon worldwide. Due to a shortage of trained doctors, access
to licensed allopathic doctors is limited in India's villages. Pharmacists and
unlicensed medical providers are commonly the primary sources of healthcare.
Patients themselves are also key participants in the decision to treat an illness
with antibiotics. Thus, better understanding of the patient-provider interactions
that may contribute to patients' inappropriate use of antibiotics is critical to
reducing these practices in urban and rural Indian villages. METHODS: We
conducted a qualitative study of the social determinants of antibiotic use among
twenty community members in Haryana, India. Semi-structured interview questions
focused on two domains: typical antibiotic use and the motivation behind these
practices. A cross-sectional pilot survey investigated the same twenty
participants' understanding and usage of antibiotics. Interview and open-ended
survey responses were translated, transcribed, and coded for themes. RESULTS:
Antibiotics and the implications of their misuse were poorly understood by study
participants. No participant was able to correctly define the term antibiotics.
Participants with limited access to an allopathic doctor, either for logistic or
economic reasons, were more likely to purchase medications directly from a
pharmacy without a prescription. Low income participants were also more likely to
prematurely stop antibiotics after symptoms subsided. Regardless of income,
participants were more likely to seek an allopathic doctor for their children
than for themselves. CONCLUSIONS: The prevalent misuse of antibiotics among these
community members reinforces the importance of conducting research to develop
effective strategies for stemming the tide of antibiotic resistance in India's
villages.
PMID- 28420366
TI - Pirfenidone attenuates bleomycin-induced pulmonary fibrosis in mice by regulating
Nrf2/Bach1 equilibrium.
AB - BACKGROUND: Oxidative stress is one of the important factors involved in the
pathogenesis of idiopathic pulmonary fibrosis (IPF). The equilibrium of Nuclear
factor-erythroid-related factor 2 (Nrf2)/[BTB (broad-complex, tramtrack and bric
a-brac) and CNC (cap'n'collar protein) homology 1, Bach1] determines the
expression level of antioxidant factors, further regulating the function of
oxidation/antioxidation capacity. Pirfenidone (PFD) is one of two currently for
IPF therapy approved drugs. PFD regulates intracellular antioxidants, inhibits
secretion of inflammatory cytokines and collagen synthesis. However the
mechanisms of its antioxidant effects remain elusive. METHODS: Effects of PFD
treatment were studied in mouse lung fibroblasts (MLF) following induction by
transforming-growth factor beta 1 (TGF-beta1) and in mice following bleomycin
induced lung fibrosis. The mRNA and protein levels of oxidative stress-related
factors Nrf2/Bach1 and their downstream antioxidant factors heme oxygenase-1 (Ho
1) and glutathione peroxidase 1 (Gpx1) were determined by RT-PCR and Western
blot. Fibrosis-related cytokines interleukin-6 (IL-6) and myofibroblast markers
type 1 collagen alpha1 (COL1A1) levels in supernate of MLF, serum, and
bronchoalveolar lavage fluid (BALF) as well as malondialdehyde (MDA) in serum and
BALF were detected by ELISA, reactive oxygen species (ROS) generation was
measured by 2',7'- dichlorofluorescin diacetate (DCFH-DA) assay and lung
pathological/morphological alterations in mice were observed by HE and Masson to
assess the antioxidant mechanism and therapeutic effects on pulmonary fibrosis
induced by bleomycin. RESULTS: PFD inhibited Bach1 mRNA and protein expressions
in mouse lung fibroblasts induced by TGF-beta1 and lung tissues with pulmonary
fibrosis induced by bleomycin. Furthermore, it improved Nrf2, Ho-1 and Gpx1 mRNA
and protein expressions. After PFD treatment, COL1A1and IL-6 levels in supernate
of MLF, serum, and BALF as well as ROS in lung tissues and MDA in serum and BALF
from a mouse with pulmonary fibrosis were significantly decreased, and the
infiltration of lung inflammatory cells and fibrosis degree were alleviated.
CONCLUSIONS: Theraputic effects of PFD for IPF were involved in Nrf2/Bach1
equilibrium which regulated the capacity of oxidative stress. The study provided
new insights into the antioxidant mechanism of PFD.
PMID- 28420367
TI - Rationale and methods of the iFightDepression study: A double-blind, randomized
controlled trial evaluating the efficacy of an internet-based self-management
tool for moderate to mild depression.
AB - BACKGROUND: During the last decade online interventions have emerged as a
promising approach for patients with mild/moderate depressive symptoms, reaching
at large populations and representing cost-effective alternatives. The main
objective of this double-blind, randomized controlled trial is to examine the
efficacy of an internet-based self-management tool (iFightDepression) for mild to
moderate depression as an add-on to treatment as usual (TAU) versus internet
based psychoeducation plus TAU. METHODS: A total of 310 participants with major
depression disorder (MDD) will be recruited at four different mental-health
facilities in Spain. Participants will be randomly allocated to one of two study
arms: iFightDepression (iFD) tool + TAU vs. internet-based psychoeducation + TAU.
Both interventions last for 8 weeks and there is a 12 weeks follow up. The
primary outcome measure is changes in depressive symptoms assessed with the
Hamilton Depression Rating Scale. Additionally, pre-post interventions
assessments will include socio-demographic data, a brief medical and clinical
history and self-reported measures of depressive symptoms, quality of life,
functional impairments and satisfaction with the iFD tool. DISCUSSION:
iFightDepression is an easy-prescribed tool that could increase the efficacy of
conventional treatment and potentially reach untreated patients, shortening
waiting lists to receive psychological treatment. Confirming the efficacy of the
iFD internet-based self-management tool as an add-on treatment for individuals
with mild to moderate depression will be clinically-relevant. TRIAL REGISTRATION:
Registration number NCT02312583 . Clinicaltrials.gov . December 4, 2014.
PMID- 28420368
TI - Outcomes following percutaneous coronary revascularization among South Asian and
Chinese Canadians.
AB - BACKGROUND: Previous data suggest significant ethnic differences in outcomes
following percutaneous coronary revascularization (PCI), though previous studies
have focused on subgroups of PCI patients or used administrative data only. We
sought to compare outcomes in a population-based cohort of men and women of South
Asian (SA), Chinese and "Other" ethnicity. METHODS: Using a population-based
registry, we identified 41,792 patients who underwent first revascularization via
PCI in British Columbia, Canada, between 2001 and 2010. We defined three ethnic
groups (SA, 3904 [9.3%]; Chinese, 1345 [3.2%]; and all "Others" 36,543 [87.4%]).
Differences in mortality, repeat revascularization (RRV) and target vessel
revascularization (TVR), at 30 days and from 31 days to 2 years were examined.
RESULTS: Adjusted mortality from 31 days to 2 years was lower in Chinese patients
than in "Others" (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.53
0.97), but not different between SAs and "Others". SA patients had higher RRV at
30 days (adjusted odds ratio [OR] 1.30; 95% CI: 1.12-1.51) and from 31 days to 2
years (adjusted hazard ratio [HR] 1.17; 95% CI: 1.06-1.30) compared to "Others".
In contrast, Chinese patients had a lower rate of RRV from 31 days to 2 years
(adjusted HR 0.79; 95% CI: 0.64-0.96) versus "Others". SA patients also had
higher rates of TVR at 30 days (adjusted OR 1.35; 95% CI: 1.10-1.66) and from 31
days to 2 years (adjusted HR 1.19; 95% CI: 1.06-1.34) compared to "Others".
Chinese patients had a lower rate of TVR from 31 days to 2 years (adjusted HR
0.76; 95% CI: 0.60-0.96). CONCLUSIONS: SA had higher RRV and TVR rates while
Chinese Canadians had lower rates of long-term RRV, compared to those of "Other"
ethnicity. Further research to elucidate the reasons for these differences could
inform targeted strategies to improve outcomes.
PMID- 28420369
TI - Improving the effectiveness of sickness benefit case management through a public
private partnership? A difference-in-difference analysis in eighteen Danish
municipalities.
AB - BACKGROUND: The aim of this study was to investigate whether a multidimensional
public-private partnership intervention, focussing on improving the quality and
efficiency of sickness benefit case management, reduced the sickness benefit
duration and the duration until self-support. METHODS: We used a difference-in
difference (DID) design with six intervention municipalities and 12 matched
control municipalities in Denmark. The study sample comprised 282,103 sickness
benefit spells exceeding four weeks. The intervention group with 110,291 spells
received the intervention, and the control group with 171,812 spells received
ordinary sickness benefit case management. Using register data, we fitted Cox
proportional hazard ratio models, estimating hazard ratios (HR) and confidence
intervals (CI). RESULTS: We found no joint effect of the intervention on the
sickness benefit duration (HR 1.02, CI 0.97-1.07) or the duration until self
support (HR 0.99, CI 0.96-1.02). The effect varied among the six municipalities,
with sickness benefit HRs ranging from 0.96 (CI 0.93-1.00) to 1.13 (CI 1.08-1.18)
and self-support HRs ranging from 0.91 (CI 0.82-1.00) to 1.11 (CI 1.06-1.17).
CONCLUSIONS: Compared to receiving ordinary sickness benefit management the
intervention had on average no effect on the sickness benefit duration or
duration until self-support. However, the effect varied considerably among the
six municipalities possibly due to differences in the implementation or the
complexity of the intervention.
PMID- 28420370
TI - Neuroprotective effect of Demethoxycurcumin, a natural derivative of Curcumin on
rotenone induced neurotoxicity in SH-SY 5Y Neuroblastoma cells.
AB - BACKGROUND: Mitochondrial dysfunction and oxidative stress are the main toxic
events leading to dopaminergic neuronal death in Parkinson's disease (PD) and
identified as vital objective for therapeutic intercession. This study
investigated the neuro-protective effects of the demethoxycurcumin (DMC), a
derivative of curcumin against rotenone induced neurotoxicity. METHODS: SH-SY5Y
neuroblastoma cells are divided into four experimental groups: untreated cells,
cells incubated with rotenone (100 nM), cells treated with DMC (50 nM) + rotenone
(100 nM) and DMC alone treated. 24 h after treatment with rotenone and 28 h after
treatment with DMC, cell viability was assessed using the MTT assay, and levels
of ROS and MMP, plus expression of apoptotic protein were analysed. RESULTS:
Rotenone induced cell death in SH-SY5Y cells was significantly reduced by DMC
pretreatment in a dose-dependent manner, indicating the potent neuroprotective
effects of DMC. Rotenone treatment significantly increases the levels of ROS,
loss of MMP, release of Cyt-c and expression of pro-apoptotic markers and
decreases the expression of anti-apoptotic markers. CONCLUSIONS: Even though the
results of the present study indicated that the DMC may serve as a potent
therapeutic agent particularly for the treatment of neurodegenerative diseases
like PD, further pre-clinical and clinical studies are required.
PMID- 28420371
TI - Effect of pulmonary arteriovenous malformations on the mechanical properties of
the lungs.
AB - BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are present in
approximately 15-50% individuals with hereditary hemorrhagic telangiectasia
(HHT). They may be isolated but more often are multiple. The goal of this study
was to evaluate the influence of PAVMs on lung mechanical properties. METHODS: We
reviewed the files of all adult patients (age >= 18 years) referred to our Center
for evaluation of HHT between 2005 and 2013. The diagnosis of HHT was based on
the Curacao criteria and/or the presence of a pathogenic mutation. Exclusion
criteria included: chronic cardiac or lung disease (i.e. asthma or COPD),
suspicion of pulmonary hypertension on echocardiography, current or past smoking
(>10 pack-years), history of thoracic surgery, previous treatment of PAVMs by
embolotherapy, lung infection or thromboembolic disease in the past 3 months,
pregnancy and obesity (BMI > 30 kg/m2). Chest high resolution CT-scan and
pulmonary function tests were performed the same day in all patients as part of
our routine work-up. RESULTS: One hundred and fifty five patients with HHT were
included (age: 44.4 +/- 16.7 yrs - mean +/- SD -; males: 39%). Eighty eight
patients had no PAVM, 45 had 1-3 PAVMS and 22 had at least 4 PAVMs. Thirty eight
patients had unilateral PAVMs and 29 bilateral PAVMs. We found no statistical
relationship between the number, the size and the laterality of PAVMs and results
of lung flows and volumes. CONCLUSION: We found no evidence that PAVMs have a
significant influence on lung mechanical properties as measured using routine
pulmonary function tests in adult patients with HHT, even in case of numerous,
macroscopic or bilateral malformations.
PMID- 28420372
TI - Erratum to: Trends in HIV counseling and testing uptake among married individuals
in Rakai, Uganda.
PMID- 28420373
TI - Early outbreak detection by linking health advice line calls to water
distribution areas retrospectively demonstrated in a large waterborne outbreak of
cryptosporidiosis in Sweden.
AB - BACKGROUND: In the winter and spring of 2011 a large outbreak of
cryptosporidiosis occurred in Skelleftea municipality, Sweden. This study
summarizes the outbreak investigation in terms of outbreak size, duration,
clinical characteristics, possible source(s) and the potential for earlier
detection using calls to a health advice line. METHODS: The investigation
included two epidemiological questionnaires and microbial analysis of samples
from patients, water and other environmental sources. In addition, a
retrospective study based on phone calls to a health advice line was performed by
comparing patterns of phone calls between different water distribution areas.
RESULTS: Our analyses showed that approximately 18,500 individuals were affected
by a waterborne outbreak of cryptosporidiosis in Skelleftea in 2011. This makes
it the second largest outbreak of cryptosporidiosis in Europe to date.
Cryptosporidium hominis oocysts of subtype IbA10G2 were found in patient and
sewage samples, but not in raw water or in drinking water, and the initial
contamination source could not be determined. The outbreak went unnoticed to
authorities for several months. The analysis of the calls to the health advice
line provides strong indications early in the outbreak that it was linked to a
particular water treatment plant. CONCLUSIONS: We conclude that an earlier
detection of the outbreak by linking calls to a health advice line to water
distribution areas could have limited the outbreak substantially.
PMID- 28420374
TI - Prevalence and associated factors of common mental disorders among Ethiopian
migrant returnees from the Middle East and South Africa.
AB - BACKGROUND: Ethiopian migrants to the Middle East and South Africa experience a
range of problems at various stages of their migration including overwork, sleep
deprivation, denial of food, emotional abuse, difficulty adapting to the host
culture, salary denial, sexual abuse, labor exploitation, confiscation of their
travel documents, confinement, denial of medication, lack of access to legal
service and degrading attitude by employers, traffickers and smugglers. These
experiences can be associated with different types of mental disorders. This
study sought to determine the prevalence of common mental disorders (CMD) and
socio-demographic and other migration related associated factors among Ethiopian
migrant returnees from the Middle East and South Africa. METHOD: A cross
sectional study was conducted using non-probability (i.e. purposive, availability
and snowball) sampling techniques. Migrant returnees (n = 1036) were contacted
individually at their homes in eight high prevalent immigrant returnee locations
in Ethiopia. Common mental disorders were assessed using the self-reporting
questionnaire (SRQ-20) and a structured questionnaire was employed to collect
data on socio-demographic and migration related characteristics. Data were
analyzed using descriptive statistics, univariate logistic regression, and
multivariable logistic regression. RESULTS: The prevalence of CMD among migrant
returnees was found to be 27.6%. Highly prevalent specific CMD symptoms included
headaches, poor appetite, being tired, sleeping problems, and feeling unhappy or
nervous. Being originally from Amhara and Oromia regions, being Christian, being
divorced, not receiving salary on time, not being able to contact family, unable
to prepare for domestic labor abroad, lack of cross- cultural awareness, and lack
of knowledge and skills for work were all important risk factors for CMD.
Migrants experienced adversities at different stages of their migration which are
associated with psychological distress and even to long term mental illnesses.
CONCLUSIONS: CMD symptoms were found to be prevalent among Ethiopian migrant
returnees. As pre-migration factors are associated with CMD symptoms, pre
departure training could be useful to mitigate the risk factors. Creating and
routinely arranging mental health interventions and rehabilitation services are
advisable for returnees who are screened for, or diagnosed with, mental health
problems.
PMID- 28420375
TI - Silent progression in patients with rheumatoid arthritis: is DAS28 remission an
insufficient goal in RA? Results from the German Remission-plus cohort.
AB - BACKGROUND: Remission is arguably the ultimate therapeutic goal in rheumatoid
arthritis (RA). Applying modern strategies, clinical remission can be achieved in
a substantial number of patients with early RA (ERA). Even in those patients, the
number and scope of erosions can increase. We, therefore, investigated the value
of MRI for the detection of radiological progression in patients with DAS28
improvement and/or clinical remission of the German Remission-plus cohort.
METHODS: Data-sets of 80 RA patients (according to 2010 ACR/EULAR criteria) from
the Remission-plus study cohort, who fulfilled the following criteria, were
retrospectively analysed: availability of two consecutive MRI scans (low-field
MRI, follow-up interval 1 year) of the clinically dominant hand and wrist, and
the presence of DAS28 (CRP) scores at both time points, which was used to assess
disease activity. RESULTS: Seventy-one of the 80 investigated patients presented
a numerical improvement of the DAS28 (CRP) after 12 months (DAS28(CRP) T0 average
(O) 4.96, SD 1.2; DAS28 T4 (12 month) O 2.6, SD 1.0), 73% of them also improved
in the RAMRIS-Score, while 24% demonstrated an increase despite DAS28 improvement
and 3% showed equal values. 48% of patients who improved in the DAS28 reached
EULAR remission. 41% of these patients had an increase in the RAMRIS Erosion
subscore after 12 months. When considering EULAR response criteria (non-response
(n = 7), moderate response (n = 19), good response (n = 45)), an increase of
erosions was found in 71.4% of non-responders, 52.6% of moderate responders, and
31.1% of good responders after 12 months, all compared to baseline. CONCLUSION:
Up to 40% of patients in this study demonstrated a progressive erosive disease
detected by MRI despite DAS28 improvement or EULAR remission. Future studies are
needed to determine the prognostic clinical impact of disease progression in MRI
despite clinical remission, and to investigate if DAS28 remission may be an
insufficient therapeutic goal and should be accompanied by MRI remission
criteria.
PMID- 28420376
TI - Workflow standardization of a novel team care model to improve chronic care: a
quasi-experimental study.
AB - BACKGROUND: Team-based chronic care models have not been widely adopted in
community settings, partly due to their varying effectiveness in randomized
control trials, implementation challenges, and concerns about physician
acceptance. The Palo Alto Medical Foundation designed and implemented "Champion,"
a novel team-based model that includes new standard work (e.g. proactive patient
outreach, pre-visit schedule grooming, depression screening, care planning,
health coaching) to support patients' self-management of hypertension and
diabetes. We investigated whether Champion improved clinical outcomes. METHODS:
We conducted a quasi-experimental study comparing the Champion clinic-level
intervention (n = 38 physicians) with a usual care clinic (n = 37 physicians) in
Northern California. The primary outcomes, blood pressure and glycohemoglobin
(A1c), were analyzed using a piecewise linear growth curve model for patients
exposed to a Champion physician visit (n = 3156) or usual care visit (n = 8034)
in the two years prior and one year post implementation. Secondary outcomes were
provider experience, compared at baseline and 12 months in both the intervention
and usual care clinics using multi-level ordered logistic modeling, and
electronic health record based fidelity measures. RESULTS: Compared to usual
care, in the first 6 months after a Champion physician visit, diabetes patients
aged 18-75 experienced an additional -1.13 mm Hg (95% CI: -2.23 to -0.04) decline
in diastolic blood pressure and -0.47 (95% CI: -0.61 to -0.33) decline in A1c.
There were no additional improvements in blood pressure or A1c 6 to 12 months
post physician visit. At 12 months, Champion physicians reported improved
experience with managing chronic care patients in 6 of 7 survey items (p < 0.05),
but compared to usual, this difference was only statistically significant for one
item (p < 0.05). Fidelity to standard work was uneven; depression screening was
the most commonly documented element (85% of patients), while care plans were the
least (30.8% of patients). CONCLUSIONS: Champion standard work improved glycemic
control over the first 6 months and physicians' experience with managing chronic
care; changes in blood pressure were not clinically meaningful. Our results
suggest the need to understand the relationship between the intervention, the
contextual features of implementation, and fidelity to further improve chronic
disease outcomes. This study was retrospectively registered with the ISRCTN
Registry on March 15, 2017 (ISRCTN11341906).
PMID- 28420377
TI - The association between child maltreatment and emotional, cognitive, and physical
health functioning in Vietnam.
AB - BACKGROUND: There is a paucity of research on correlates of child maltreatment in
limited-resource countries with a relatively high tolerance of harsh discipline.
This Vietnamese study aimed to investigate associations between different types
of child maltreatment and child emotional, cognitive, and physical health
functioning as well as moderation effects of gender and ethnicity. METHODS: This
cross-sectional study was conducted with 1851 randomly selected students aged 12
17 years. Both self-report and more objective measures (weight, height, study
ranking, and a memory test) were used. RESULTS: All types of child maltreatment
were associated with emotional dysfunctioning. Life time and past year
experiences of physical abuse and life time experiences of sexual abuse and
neglect were related to poorer perceived physical health. The study did not find
associations between any type of child maltreatment and overweight or underweight
status. Regarding cognitive functioning, life time experience of sexual abuse and
neglect were related to poorer working memory performance. Noticeably, emotional
abuse was related to better academic performance, which might be an indication of
"tiger parenting" practice in Vietnam, implying academic performance stimulation
at the expense of emotional security. No significant moderation effects by gender
and ethnicity were found. CONCLUSION: Even in a culture in which harsh discipline
is normative, child maltreatment was related to negative aspects of child
wellbeing including emotional, cognitive, and physical health functioning.
Efficient and low-cost interventions on child maltreatment should be developed
and conducted in Vietnam as well as other countries with similar contexts.
PMID- 28420378
TI - A cross-sectional survey assessing factors associated with reading cancer
screening information: previous screening behaviour, demographics and decision
making style.
AB - BACKGROUND: There is broad agreement that cancer screening invitees should know
the risks and benefits of testing before deciding whether to participate. In
organised screening programmes, a primary method of relaying this information is
via leaflets provided at the time of invitation. Little is known about why
individuals do not engage with this information. This study assessed factors
associated with reading information leaflets provided by the three cancer
screening programmes in England. METHODS: A cross-sectional survey asked
screening-eligible members of the general population in England about the
following predictor variables: uptake of previous screening invitations,
demographic characteristics, and 'decision-making styles' (i.e. the extent to
which participants tended to make decisions in a way that was avoidant, rational,
intuitive, spontaneous, or dependent). The primary outcome measures were the
amount of the leaflet that participants reported having read at their most recent
invitation, for any of the three programmes for which they were eligible.
Associations between these outcomes and predictor variables were assessed using
binary or ordinal logistic regression. RESULTS: After exclusions, data from 275,
309, and 556 participants were analysed in relation to the breast, cervical, and
bowel screening programmes, respectively. Notable relationships included
associations between regularity of screening uptake and reading (more of) the
information leaflets for all programmes (e.g. odds ratio: 0.16 for participants
who never/very rarely attended breast screening vs. those who always attended
previously; p = .009). Higher rational decision-making scores were associated
with reading more of the cervical and bowel screening leaflets (OR: 1.13, p <
.0005 and OR: 1.11, p = .045, respectively). Information engagement was also
higher for White British participants compared with other ethnic groups for
breast (OR: 3.28, p = .008) and bowel (OR: 2.58, p = .015) information; an
opposite relationship was observed for older participants (OR: 0.96, p = .048;
OR: 0.92, p = .029). CONCLUSIONS: Interventions that increase screening uptake
may also increase subsequent engagement with information. Future research could
investigate how to improve engagement at initial invitations. There may also be
scope to reduce barriers to accessing non-English information and alternative
communication strategies may benefit participants who are less inclined to weigh
up advantages and disadvantages as part of their decision-making.
PMID- 28420379
TI - Distribution and symmetrical patellofemoral pain patterns as revealed by high
resolution 3D body mapping: a cross-sectional study.
AB - BACKGROUND: Detailed pain mapping of extent and distribution in individuals with
patellofemoral pain (PFP) within and around a complex structure such as the knee
has yet to be explored. METHODS: Perceptions of on-going pain from adolescents
and young adults (N = 35) with long-standing (>10 months) PFP were collected on
high-resolution 3D digital body-schema of the knees. Location, area of pain, pain
intensity, laterality, worse side of knee pain, symptom duration, and symmetry in
bilateral knee pain were recorded. A threshold for naturally occurring variations
in symmetrical knee pain drawings were collected from 18 healthy controls and
used in combination with the development a symmetry index (0-1) to create a fuzzy
rule for classifying symmetrical and non-symmetrical PFP patterns as compared to
a PFP expert. The symmetry index was computed and tested using a correlation
coefficient alone or in combination with the Jaccard index and the true and false
positive rates (TPR and FPR, respectively) determined. RESULTS: The peripatellar
region was the common report of pain location however, novel and nonconforming
PFP patterns were identified and the majority of individuals (22 of 27) with
bilateral PFP expressed highly-symmetric mirror-image pain. Individuals with
symptom duration of 5 years or more had a greater area of pain, compared to those
with symptoms for less than 5 years. The total area of pain was correlated to
symptom duration for those with extended symptoms durations and a progression
towards an "O" shaped pattern emerged. A TPR of 100% for identifying symmetrical
knee pain patterns was found however the expert PFP tended to be stricter, as
reflected in FPR of 20%. CONCLUSIONS: A high proportion of PFP patterns or
symptoms occur in mirrored locations and are exceptionally symmetrical, and long
duration of symptoms appear to converge to an 'O' shape. Classifying symmetrical
pain patterns is subjective however simple fuzzy rules and correlations can be
used to increase objectivity. This study highlights a gap in knowledge of PFP
symptom presentation, reveals what may be a natural progression of symptoms, and
provides valuable clinical insight for both pain management and treatment.
PMID- 28420380
TI - Educational status as determinant of men's knowledge about vasectomy in Dangila
town administration, Amhara region, Northwest Ethiopia.
AB - BACKGROUND: Although vasectomy is effective and less expensive contraceptive
method, only few men are using it in Africa. The main reason for low level use
may be low knowledge about vasectomy among men. Only few studies tried to
investigate level of knowledge of vasectomy among married men in Ethiopia. But
these studies have limitations in measuring knowledge. This study was therefore
designed to assess knowledge of vasectomy among married men in Dangila town.
METHOD: A community based cross sectional study was conducted in Dangila town.
Sample size was calculated using OpenEPI online sample size calculator for
population based surveys. Multistage sampling technique was employed to recruit
the study participants. Data collectors interviewed selected men using structured
Amharic questionnaire from June to July, 2014. Two days training was given to
data collectors and supervisors. Data were entered and analyzed using SPSS
version 16. Binary logistic regression analysis was done to identify determinants
of knowledge about vasectomy. RESULT: A total of 872 men were interviewed. About
75% of men reported that they had ever heard about vasectomy. Men mentioned
friends as main source of information for vasectomy. Among those who had ever
heard, only 60.8% defined vasectomy correctly. About 20% defined vasectomy as "it
is making the man impotent." Similarly about 16% equated vasectomy with
castration. In this study, only 44.8% of men were knowledgeable about vasectomy.
Married men who completed secondary education were 4.10(95%CI; 2.48 - 6.75) times
more likely to be knowledgeable about vasectomy compared to those who did not
attend formal education. Those who attended above secondary education were
5.73(95%CI 3.76 - 8.73) times more likely to be knowledgeable about vasectomy
compared to those who did not attend formal education. CONCLUSION: Level of
knowledge about vasectomy among married men in Dangla town was low and
educational status was an important predictor of knowledge about vasectomy.
Efforts are needed to improve knowledge of men about vasectomy. In addition,
encouraging boys to complete secondary education may help improve knowledge of
men about vasectomy.
PMID- 28420381
TI - Operations research in global health: a scoping review with a focus on the themes
of health equity and impact.
AB - BACKGROUND: Operations research (OR) is a discipline that uses advanced
analytical methods (e.g. simulation, optimisation, decision analysis) to better
understand complex systems and aid in decision-making. Herein, we present a
scoping review of the use of OR to analyse issues in global health, with an
emphasis on health equity and research impact. A systematic search of five
databases was designed to identify relevant published literature. A global
overview of 1099 studies highlights the geographic distribution of OR and common
OR methods used. From this collection of literature, a narrative description of
the use of OR across four main application areas of global health - health
systems and operations, clinical medicine, public health and health innovation -
is also presented. The theme of health equity is then explored in detail through
a subset of 44 studies. Health equity is a critical element of global health that
cuts across all four application areas, and is an issue particularly amenable to
analysis through OR. Finally, we present seven select cases of OR analyses that
have been implemented or have influenced decision-making in global health policy
or practice. Based on these cases, we identify three key drivers for success in
bridging the gap between OR and global health policy, namely international
collaboration with stakeholders, use of contextually appropriate data, and varied
communication outlets for research findings. Such cases, however, represent a
very small proportion of the literature found. CONCLUSION: Poor availability of
representative and quality data, and a lack of collaboration between those who
develop OR models and stakeholders in the contexts where OR analyses are intended
to serve, were found to be common challenges for effective OR modelling in global
health.
PMID- 28420382
TI - Effect of tDCS stimulation of motor cortex and cerebellum on EEG classification
of motor imagery and sensorimotor band power.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a technique for
brain modulation that has potential to be used in motor neurorehabilitation.
Considering that the cerebellum and motor cortex exert influence on the motor
network, their stimulation could enhance motor functions, such as motor imagery,
and be utilized for brain-computer interfaces (BCIs) during motor
neurorehabilitation. METHODS: A new tDCS montage that influences cerebellum and
either right-hand or feet motor area is proposed and validated with a simulation
of electric field. The effect of current density (0, 0.02, 0.04 or 0.06 mA/cm2)
on electroencephalographic (EEG) classification into rest or right-hand/feet
motor imagery was evaluated on 5 healthy volunteers for different stimulation
modalities: 1) 10-minutes anodal tDCS before EEG acquisition over right-hand or
2) feet motor cortical area, and 3) 4-seconds anodal tDCS during EEG acquisition
either on right-hand or feet cortical areas before each time right-hand or feet
motor imagery is performed. For each subject and tDCS modality, analysis of
variance and Tukey-Kramer multiple comparisons tests (p <0.001) are used to
detect significant differences between classification accuracies that are
obtained with different current densities. For tDCS modalities that improved
accuracy, t-tests (p <0.05) are used to compare MU and beta band power when a
specific current density is provided against the case of supplying no
stimulation. RESULTS: The proposed montage improved the classification of right
hand motor imagery for 4 out of 5 subjects when the highest current was applied
for 10 minutes over the right-hand motor area. Although EEG band power changes
could not be related directly to classification improvement, tDCS appears to
affect variably different motor areas on MU and/or beta band. CONCLUSIONS: The
proposed montage seems capable of enhancing right-hand motor imagery detection
when the right-hand motor area is stimulated. Future research should be focused
on applying higher currents over the feet motor cortex, which is deeper in the
brain compared to the hand motor cortex, since it may allow observation of
effects due to tDCS. Also, strategies for improving analysis of EEG respect to
accuracy changes should be implemented.
PMID- 28420383
TI - PPBP and DEFA1/DEFA3 genes in hyperlipidaemia as feasible synergistic
inflammatory biomarkers for coronary heart disease.
AB - BACKGROUND: Coronary heart disease (CHD) is an important complication of
atherosclerosis. Biomarkers, which associate with CHD development, are potential
to predict CHD risk. To determine whether genes showing altered expression in
hyperlipidaemia (H) and coronary heart disease (CHD) patients compared with
controls could be CHD risk biomarkers. METHODS: Control, H, and CHD groups
represented atherosclerosis to CHD development. Gene profiling was investigated
in peripheral blood mononuclear cells using DNA microarrays. Eight selected genes
expressed only in H and CHD groups were validated by real-time quantitative
reverse transcription PCR and plasma protein determination. RESULTS: alpha
defensin (DEFA1/DEFA3), pro-platelet basic protein (PPBP), and beta and alpha2
hemoglobin mRNA expression was significantly increased in H and CHD groups
compared with controls, but only plasma PPBP and alpha-defensin proteins were
correspondingly increased. CONCLUSION: PPBP and DEFA1/DEFA3 could be potential
CHD biomarkers in Thai hyperlipidaemia patients.
PMID- 28420384
TI - Molecular characteristic of mcr-1 producing Escherichia coli in a Chinese
university hospital.
AB - BACKGROUND: Colistin has been considered as a last-line treatment option in
severe infections caused by multidrug-resistant (MDR) gram-negative pathogens.
However, the emergence of the mobile colistin resistance gene (mcr-1) has
challenged this viewpoint. The aim of this study is to explore the prevalence of
mcr-1 in Escherichia coli (E. coli) in a Chinese teaching hospital, and
investigate their molecular characteristics. METHODS: A total of 700 E. coli
isolates were used to screen mcr-1 by PCR and sequencing in a Chinese university
hospital from August 2014 to August 2015. Susceptibility test of mcr-1-producing
isolates was determined by Vitek -2 Compact system. 26 virulence factors (VFs),
phylogenetic groups, Multi-locus sequence typing (MLST), and DNA Fingerprinting
(ERIC-PCR) of strains were investigated by PCR. RESULTS: Four (0.6%) mcr-1
producing E. coli isolates were found in this study. The results of antibiotic
susceptibility test showed that all four isolates were resistant to colistin,
ciprofloxacin, levofloxacin, cefazolin, and trimethoprim/sulfamethoxazole, and
were susceptible to amikacin, ertapenem and imipenem. In addition, all 4 isolates
exhibited high-level resistance to aztreonam, cefotaxime and gentamicin. The
numbers of VFs contained in mcr-1 positive isolates were no more than 4 in our
study. MLST result demonstrated that these isolates were assigned to two sequence
types: ST156 and ST167. The result of phylogenetic analysis showed that four mcr
1-positive isolates belong to two phylogenetic groups: A and B1 group. ERIC-PCR
showed that four mcr-1 positive strains were categorized into three different
genotypes. CONCLUSIONS: Our study demonstrated a low prevalence of mcr-1 in E.
coli clinical isolates in a Chinese teaching hospital, and we have gained
insights into the molecular characteristics of these mcr-1-positive strains.
Increasing the surveillance of these infections, as well as taking effective
infection control measures are urgently needed to take to control the
transmission of mcr-1 gene.
PMID- 28420385
TI - Frontotemporal dementia as a comorbidity to idiopathic normal pressure
hydrocephalus (iNPH): a short review of literature and an unusual case.
AB - Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal
pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present
with similar symptoms. These include decline in executive functions, psychomotor
slowness, and behavioural and personality changes. Ventricular enlargement is a
key radiological finding in iNPH that may also be present in bvFTD caused by the
C9ORF72 expansion mutation. Due to this, bvFTD has been hypothesized as a
potential comorbidity to iNPH but bvFTD patients have never been identified in
studies focusing in clinical comorbidities with iNPH. Here we describe a patient
with the C9ORF72 expansion-associated bvFTD who also showed enlarged ventricles
on brain imaging. The main clinical symptoms were severe gait disturbances and
psychiatric problems with mild cognitive decline. Cerebrospinal fluid removal
increased the patient's walking speed, so a ventriculoperitoneal shunt was
placed. After insertion of the shunt, there was a significant improvement in
walking speed as well as mild improvement in cognitive function but not in
neuropsychiatric symptoms relating to bvFTD. Comorbid iNPH should be considered
in bvFTD patients who have enlarged ventricles and severely impaired gait.
PMID- 28420386
TI - Sedation levels in dogs: a validation study.
AB - BACKGROUND: The aim of this study was to assess validation evidence for a
sedation scale for dogs. We hypothesized that the chosen sedation scale would be
unreliable when used by different raters and show poor discrimination between
sedation protocols. A sedation scale (range 0-21) was used to score 62 dogs
scheduled to receive sedation at two veterinary clinics in a prospective trial.
Scores recorded by a single observer were used to assess internal consistency and
construct validity of the scores. To assess inter-rater reliability, video
recordings of sedation assessment were randomized and blinded for viewing by 5
raters untrained in the scale. Videos were also edited to allow assessment of
inter-rater reliability of an abbreviated scale (range 0-12) by 5 different
raters. RESULTS: Both sedation scales exhibited excellent internal consistency
and very good inter-rater reliability (full scale, intraclass correlation
coefficient [ICCsingle] = 0.95; abbreviated scale, ICCsingle = 0.94). The full
scale discriminated between the most common protocols: dexmedetomidine
hydromorphone (median [range] of sedation score, 11 [1-18], n = 20) and
acepromazine-hydromorphone (5 [0-15], n = 36, p = 0.02). CONCLUSIONS: The
hypothesis was rejected. Full and abbreviated scales showed excellent internal
consistency and very good reliability between multiple untrained raters. The full
scale differentiated between levels of sedation.
PMID- 28420387
TI - Effects of host restriction factors and the HTLV-1 subtype on susceptibility to
HTLV-1-associated myelopathy/tropical spastic paraparesis.
AB - BACKGROUND: Although human T-lymphotropic virus type 1 (HTLV-1) infection is a
prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic
paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been
reported. In this study, we examined whether HAM/TSP patients had the disease
specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1
proviruses in these patients, including familial cases. In addition, we
investigated the genetic variants of host restriction factors conferring
antiretroviral activity to determine which mutations may be related to resistance
or susceptibility to HAM/TSP. RESULTS: The subjects included 30 patients with
familial HAM/TSP (f-HAM/TSP), 92 patients with sporadic HAM/TSP (s-HAM/TSP), and
89 asymptomatic HTLV-1 carriers (ACs). In all 211 samples, 37 samples (18%) were
classified into transcontinental subtype and 174 samples (82%) were classified as
Japanese subtype. Among three groups, the percentage of transcontinental subtype
in f-HAM/TSP, s-HAM/TSP and ACs was 33, 23 and 7%, respectively. The frequency of
transcontinental subtype was significantly higher in both f-HAM/TSP (p < 0.001)
and s-HAM/TSP (p < 0.001) than in ACs. Fifty mutations in HTLV-1 sequences were
significantly more frequent in HAM/TSP patients than in ACs, however, they were
common only in transcontinental subtype. Among these mutations, ten common
mutations causing amino acid changes in the HTLV-1 sequences were specific to the
transcontinental subtype. We examined host restriction factors, and detected a
rare variant in TRIM5alpha in HAM/TSP patients. The patients with TRIM5alpha 136Q
showed lower proviral loads (PVLs) than those with 136R (354 vs. 654 copies/104
PBMC, p = 0.003). The patients with the 304L variant of TRIM5alpha had
significantly higher PVLs than those with 304H (1669 vs. 595 copies/104 PBMC, p =
0.025). We could not find any HAM/TSP-specific mutations of host restriction
factors. CONCLUSIONS: Transcontinental subtype is susceptible to HAM/TSP,
especially in familial cases. Ten common mutations causing amino acid changes in
the HTLV-1 gene were specific to the transcontinental subtype. TRIM5alpha
polymorphisms were associated with PVLs, indicating that TRIM5alpha could be
implicated in HTLV-1 replication.
PMID- 28420388
TI - Association between maternal intake of n-6 to n-3 fatty acid ratio during
pregnancy and infant neurodevelopment at 6 months of age: results of the MOCEH
cohort study.
AB - BACKGROUND & AIMS: Long-chain polyunsaturated fatty acids (LC-PUFAs) are
essential for infant neurodevelopment. The nutritional adequacy of dietary LC
PUFAs depends not only on the LC-PUFAs intake but also on the n-6 to n-3 fatty
acid ratio (n-6/n-3 PUFAs). This study aimed to identify the association between
the maternal dietary n-6/n-3 PUFAs and motor and cognitive development of infants
at 6 months of age. METHODS: We used data from 960 participants in the Mothers
and Children's Environmental Health (MOCEH) study, which is a multi-center
prospective cohort study. Dietary intake of pregnant women was assessed by a one
day 24-h recall method. Food consumption of infants was estimated based on the
volume of breast milk and weaning foods. The duration of each feed was used to
estimate the likely volume of milk consumed. Dietary intake of infants at 6
months was also assessed by a 24-h recall method. Cognitive and motor development
of infants at 6 months of age was assessed by the Korean Bayley scales of infant
development edition II (BSID-II) including the mental developmental index (MDI)
and the psychomotor developmental index (PDI). RESULTS: Maternal intakes of n-6/n
3 PUFAs and linoleic acid (LA)-to-alpha-linolenic acid (ALA) ratio (LA/ALA) were
9.7 +/- 6.3 and 11.12 +/- 6.9, respectively. Multiple regression analysis, after
adjusting for covariates, showed that n-6/n-3 PUFAs was negatively associated
with both the MDI (beta = -0.1674, P = 0.0291) and PDI (beta = -0.1947, P =
0.0380) at 6 months of age. These inverse associations were also observed between
LA/ALA and both the MDI and PDI (MDI; beta = -0.1567; P = 0.0310, PDI; beta =
0.1855; P = 0.0367). Multiple logistic regression analysis, with the covariates,
showed that infants whose mother's LA/ALA were ranked in the 2nd, 3rd, and 4th
quartile were at approximately twice the risk with more than twice the risk of
delayed performance on the PDI compared to the lowest quartile (1st vs. 2nd; OR =
2.965; 95% CI = 1.376 - 6.390, 1st vs. 3rd; OR = 3.047; 95% CI = 1.374 - 6.756
and 1st vs. 4th; OR = 2.551; 95% CI = 1.160 - 5.607). CONCLUSIONS: Both the
maternal dietary n-6/n-3 PUFAs and LA/ALA intake were significantly associated
with the mental and psychomotor development of infants at 6 months of age. Thus,
maintaining low n-6/n-3 PUFAs and LA/ALA is encouraged for women during
pregnancy.
PMID- 28420390
TI - A novel ViewRNA in situ hybridization method for the detection of the dynamic
distribution of Classical Swine Fever Virus RNA in PK15 cells.
AB - BACKGROUND: Classical swine fever (CSF) is a highly contagious fatal infectious
disease caused by classical swine fever virus (CSFV). A better understanding of
CSFV replication is important for the study of pathogenic mechanism of CSF. With
the development of novel RNA in situ Hybridization method, quantitatively
localization and visualization of the virus RNA molecular in cultured cell or
tissue section becomes very important tool to address these pivotal pathogenic
questions. In this study, we established ViewRNA ISH method to reveal the dynamic
distribution of CSFV RNA in PK15 cells. METHODS: We designed several specific
probes of CSFV RNA and reference gene beta-actin for host PK15 cells to monitor
the relative location of CSFV RNA and house-keeping gene in the infected cells.
After determining the titer of reference strain CSFV (HeBHH1/95) with the 50%
tissue culture infective dose (TCID50), we optimized the protease K concentration
and formalin fixation time to analyze the hybridization efficiency, fluorescence
intensity and repeatability. In order to measure the sensitivity of this assay,
we compared it with the fluorescent antibody test (FAT) and
immunohistochemical(IHC) method. Specificity of the ViewRNA ISH was tested by
detecting several sub genotypes of CSFV (sub genotype 1.1, 2.1, 2.2 and 2.3)
which are present in China and other normal pig infectious virus (bovine viral
diarrhea virus (BVDV), porcine parvovirus (PPV), porcine pseudorabies virus (PRV)
and porcine circovirusII(PCV-2). RESULTS: The lowest detection threshold of the
ViewRNA ISH method was 10-8, while the sensitivity of FAT and IHC were 10-5 and
10-4, respectively. The ViewRNA ISH was specific for CSFV RNA including 1.1, 2.1,
2.2 and 2.3 subtypes, meanwhile, there was no cross-reaction with negative
control and other viruses including BVDV, PPV, PRV and PCV-2. Our results showed
that after infection at 0.5 hpi (hours post inoculation, hpi), the CSFV RNA can
be detected in nucleus and cytoplasm; during 3-9 hpi, RNA was mainly distributed
in nucleus and reached a maximum at 12hpi, then RNA copy number was gradually
increased around the cell nucleus during 24-48 hpi and reached the peak at 72hpi.
CONCLUSIONS: To our knowledge, this is the first to reveal the dynamic
distribution of medium virulence CSFV RNA in PK15 cells using the ViewRNA ISH
method. The sensitivity of the ViewRNA ISH was three to four orders of magnitude
higher than that of FAT and IHC methods. The specificity experiment showed that
the ViewRNA ISH was highly specific for CSFV and no cross-reaction occurred to
negative control and other pig infectious virus. This assay is more suitable for
studying the CSFV RNA life cycle in cell nucleus. The results proved that CSFV
RNA enters into PK15 cells earlier than 0.5hpi, relative to the eclipse period of
cytoplasm is 6-9 hpi and CSFV RNA has ever existed in nucleus.
PMID- 28420389
TI - Assessment of copy number variation in genes related to drug resistance in
Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and
a systematic review of the literature.
AB - BACKGROUND: Parasite resistance to anti-malarials represents a great obstacle for
malaria elimination. The majority of studies have investigated the association
between single-nucleotide polymorphisms (SNPs) and drug resistance; however, it
is becoming clear that the copy number variation (CNV) is also associated with
this parasite phenotype. To provide a baseline for molecular surveillance of anti
malarial drug resistance in the Brazilian Amazon, the present study characterized
the genetic profile of both markers in the most common genes associated with drug
resistance in Plasmodium falciparum and Plasmodium vivax isolates. Additionally,
these data were compared to data published elsewhere applying a systematic review
of the literature published over a 20-year time period. METHODS: The genomic DNA
of 67 patients infected by P. falciparum and P. vivax from three Brazilian States
was obtained between 2002 and 2012. CNV in P. falciparum multidrug resistance
gene-1 (pfmdr1), GTP cyclohydrolase 1 (pfgch1) and P. vivax multidrug resistance
gene-1 (pvmdr1) were assessed by real-time PCR assays. SNPs in the pfmdr1 and
pfcrt genes were assessed by PCR-RFLP. A literature search for studies that
analysed CNP in the same genes of P. falciparum and P. vivax was conducted
between May 2014 and March 2017 across four databases. RESULTS: All analysed
samples of P. falciparum carried only one copy of pfmdr1 or pfgch1. Although the
pfcrt K76T polymorphism, a determinant of CQ resistance, was present in all
samples genotyped, the pfmdr1 N86Y was absent. For P. vivax isolates, an
amplification rate of 20% was found for the pvmdr1 gene. The results of the study
are in agreement with the low amplification rates for pfmdr1 gene evidenced in
the Americas and Africa, while higher rates have been described in Southeast
Asia. For P. vivax, very low rates of amplification for pvmdr1 have been
described worldwide, with exceptions in French Guiana, Cambodia, Thailand and
Brazil. CONCLUSIONS: The present study was the first to evaluate gch1 CNV in P.
falciparum isolates from Brazil, showing an absence of amplification of this gene
more than 20 years after the withdrawal of the Brazilian antifolates therapeutic
scheme. Furthermore, the rate of pvmdr1 amplification was significantly higher
than that previously reported for isolates circulating in Northern Brazil.
PMID- 28420391
TI - Interactive, open source, travel time scenario modelling: tools to facilitate
participation in health service access analysis.
AB - BACKGROUND: Modelling travel time to services has become a common public health
tool for planning service provision but the usefulness of these analyses is
constrained by the availability of accurate input data and limitations inherent
in the assumptions and parameterisation. This is particularly an issue in the
developing world where access to basic data is limited and travel is often
complex and multi-modal. Improving the accuracy and relevance in this context
requires greater accessibility to, and flexibility in, travel time modelling
tools to facilitate the incorporation of local knowledge and the rapid
exploration of multiple travel scenarios. The aim of this work was to develop
simple open source, adaptable, interactive travel time modelling tools to allow
greater access to and participation in service access analysis. RESULTS:
Described are three interconnected applications designed to reduce some of the
barriers to the more wide-spread use of GIS analysis of service access and allow
for complex spatial and temporal variations in service availability. These
applications are an open source GIS tool-kit and two geo-simulation models. The
development of these tools was guided by health service issues from a developing
world context but they present a general approach to enabling greater access to
and flexibility in health access modelling. The tools demonstrate a method that
substantially simplifies the process for conducting travel time assessments and
demonstrate a dynamic, interactive approach in an open source GIS format. In
addition this paper provides examples from empirical experience where these tools
have informed better policy and planning. CONCLUSION: Travel and health service
access is complex and cannot be reduced to a few static modeled outputs. The
approaches described in this paper use a unique set of tools to explore this
complexity, promote discussion and build understanding with the goal of producing
better planning outcomes. The accessible, flexible, interactive and responsive
nature of the applications described has the potential to allow complex
environmental social and political considerations to be incorporated and
visualised. Through supporting evidence-based planning the innovative modelling
practices described have the potential to help local health and emergency
response planning in the developing world.
PMID- 28420392
TI - Tissue tropisms, infection kinetics, histologic lesions, and antibody response of
the MR766 strain of Zika virus in a murine model.
AB - BACKGROUND: The appearance of severe Zika virus (ZIKV) disease in the most recent
outbreak has prompted researchers to respond through the development of tools to
quickly characterize transmission and pathology. We describe here another such
tool, a mouse model of ZIKV infection and pathogenesis using the MR766 strain of
virus that adds to the growing body of knowledge regarding ZIKV kinetics in small
animal models. METHODS: We infected mice with the MR766 strain of ZIKV to
determine infection kinetics via serum viremia. We further evaluated infection
induced lesions via histopathology and visualized viral antigen via
immunohistochemical labeling. We also investigated the antibody response of
recovered animals to both the MR766 and a strain from the current outbreak
(PRVABC59). RESULTS: We demonstrate that the IRF3/7 DKO mouse is a susceptible,
mostly non-lethal model well suited for the study of infection kinetics,
pathological progression, and antibody response. Infected mice presented lesions
in tissues that have been associated with ZIKV infection in the human population,
such as the eyes, male gonads, and central nervous system. In addition, we
demonstrate that infection with the MR766 strain produces cross-neutralizing
antibodies to the PRVABC59 strain of the Asian lineage. CONCLUSIONS: This model
provides an additional tool for future studies into the transmission routes of
ZIKV, as well as for the development of antivirals and other therapeutics, and
should be included in the growing list of available tools for investigations of
ZIKV infection and pathogenesis.
PMID- 28420393
TI - Medical treatment of mammary desmoid-type fibromatosis: which benefit?
AB - BACKGROUND: Breast fibromatosis is a rare disease characterized by monoclonal
fibroblast proliferation. It has no ability to metastasize but has a high local
recurrence rate and often infiltrates surrounding tissues. Surgical treatment is
the reference, but recently, new targeted therapies have emerged. We report an
original case of a patient with breast fibromatosis who received exclusive
medical treatment. Our aim was to analyze these treatments based on the clinical
and radiological outcome, iatrogenic effects, and pharmacological action. CASE
PRESENTATION: We report the case of a 19-year-old woman who developed a desmoid
type fibromatosis of the lower inner quadrant of the right breast, measuring 50 *
25 mm (i.e., a volume of 27.4 cm3). Initial surgery was not possible because of
potential esthetic and functional prejudice. Thus, she had an exclusive medical
treatment including several lines: NSAIDs with tamoxifen and triptorelin,
followed by sorafenib, then interferon alpha2b, and finally sunitinib. With
tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was
observed (57% reduction of the maximal tumoral volume). For each treatment, we
provided the clinical and radiological outcome in association with known
pharmacological action. CONCLUSIONS: TKI had been an interesting alternative
option to initial surgery, providing at least a partial response and potentially
allowing less mutilating surgery. However, no pharmacological mechanism can
unequivocally explain TKI efficacy. In general, breast fibromatosis should be
treated along with oncologist and interventional radiologists in a trans
disciplinary modality, thus offering an adapted treatment for this particular
desmoid-type fibromatosis localization.
PMID- 28420394
TI - Influence maternal background has on children's mental health.
AB - BACKGROUND: In this paper, we aim to discern how a mother's health and her
socioeconomic determinants may influence her children's mental health. In
addition to this, we also evaluate the influence of other household
characteristics and whether or not the economic downturn has heightened the
effect a parent's social gradient has on their children's mental health. METHODS:
We use samples comprised of 4-14-year-old minors from the 2006 Spanish National
Health Survey (SNHS), undertaken prior to the crisis, and the 2011 SNHS, carried
out during the crisis. The participating children's mental health is assessed
using the Strengths and Difficulties Questionnaire (SDQ). Mixed models are used
to evaluate the influence a mother's health and her socioeconomic status may have
on her children's mental health. We also add interactions to observe the effect
specific socioeconomic determinants may have had during the economic downturn.
RESULTS: The risk of a child suffering from mental health disorders increases
when their mother has mental health problems. Socioeconomic determinants also
play a role, as a low socioeconomic status (SES) increases the risk of a child
exhibiting behavioural problems, being hyperactive or antisocial, whereas when a
mother has attained a high level of education, this significantly reduces the
probability of a child having mental health problems. 'Homemaker' is the activity
status most positively related to children's mental health. The findings show
that the Spanish economic downturn has not significantly changed children's
mental health problems and the negative effects of low maternal SES are no
greater than they were before the crisis. The main difference in 2011, with
respect to 2006, is that the risk of children suffering from mental health
problems is higher when their parents are (long or short-term) unemployed.
CONCLUSIONS: In conclusion, both a mother's health and her socioeconomic status,
as well as other household characteristics, are found to be related to her
children's mental well-being. Although the crisis has not significantly changed
mental health disorders in children or the social gradient of parents in general,
at-risk children are the most negatively affected in the Spanish economic
downturn.
PMID- 28420395
TI - Characteristics of first-time varenicline users - A cross-sectional study in
Finnish quitters.
AB - BACKGROUND: Varenicline is an efficacious medicine for smoking cessation (SC) but
little is known about the characteristics of varenicline users. This study
examined the characteristics of first-time (naive) varenicline users in Finland
and compared those who had previously used SC pharmacotherapy to those who were
trying SC pharmacotherapy for the first time. METHODS: A cross-sectional survey
was conducted in Finnish community pharmacies between February 2014 and January
2015. Pharmacy customers purchasing a varenicline starter package for the first
time ever were asked to complete a questionnaire or to participate in a
structured interview conducted by the pharmacist (identical questions). The
questionnaire included questions about demographic characteristics, smoking
habits, previous cessation attempts and factors associated with varenicline use.
RESULTS: Altogether 98 people completed the survey. The majority were daily
smokers (96%, n = 94), with a history of over 10 years of regular smoking (94%, n
= 92), and a strong/very strong nicotine dependence (67%, n = 66). Half of the
participants (54%, n = 53) were trying a SC pharmacotherapy for the first time.
Demographic characteristics and smoking habits were similar between first-time
and previous users of SC medications (p > 0.05). Health centers (42%, n = 41) and
occupational health care clinics (37%, n = 36) were the most common sources of
varenicline prescriptions. The majority of participants received the prescription
for varenicline after mentioning their desire for quitting to a physician (70%, n
= 69). CONCLUSIONS: Considering the relatively large proportion of SC naive
medicine users among new users of varenicline, smokers who have previously been
reluctant to quit smoking, to use other pharmacological SC interventions, or
perhaps unaware of these options may be interested in attempting cessation with
varenicline. Most participants made the initiative to discuss their smoking with
the physician, which led to varenicline prescribing. This suggests that
physicians may not satisfactorily recognize their patients' nicotine dependence
and desire to quit, and they should more actively support patients' smoking
cessation.
PMID- 28420396
TI - Determinants of village doctors' job satisfaction under China's health sector
reform: a cross-sectional mixed methods study.
AB - BACKGROUND: To strengthen rural health workforce, the Chinese government has
launched a series of policies to promote the job satisfaction of village doctors
since the health sector reform. The purpose of this mixed-method study is to
describe village doctors' job satisfaction under the context of health sector
reform and investigate the associated factors. METHODS: Data was obtained from a
survey of village doctors across three Chinese provinces in 2014. Using a
multistage sampling process, quantitative data was collected from village doctors
through the self-administered questionnaire and analyzed by multilevel logistic
regression models. Qualitative data was collected through face-to-face semi
structured interviews on both village doctors and health managers. Theoretical
coding was then conducted to analyze qualitative data. RESULTS: Among the 1221
respondents, 48.6% felt satisfied with their job. Older village doctors with less
of a workload and under high-level integrated management were more likely to feel
satisfied with their job. Village doctors who earned the top level of monthly
income felt more satisfied, while on the county level, those who lived in
counties with the highest GDP felt less satisfied. However, enrollment in a
pension plan showed no significant difference in regards to village doctors' job
satisfaction. Among 34 participants of qualitative interviews, most believed that
age, income, and integrated management had a positive influence on the job
satisfaction, while pension plan and basic public health care policies exhibited
negative effects. Also, the increasing in availability of healthcare and health
resources along with local economic development had negative effects on village
doctors' job satisfaction. CONCLUSION: Village doctors' job satisfaction was
quite low in regards to several determinants including age, income, workload,
enrollment in a pension plan, integrated management, and county economic and
medical availability development.
PMID- 28420397
TI - Responsiveness of the short-form health survey and the Parkinson's disease
questionnaire in patients with Parkinson's disease.
AB - BACKGROUND: The responsiveness of a measurement instrument is important for
understanding its ability to detect changes in the progression of a disease. We
examined and compared the internal and external responsiveness of the 36-item
Short-Form Health Survey (SF-36) and the 39-item Parkinson's Disease
Questionnaire (PDQ-39) in patients with Parkinson's Disease (PD). METHODS:
Seventy-four patients with PD were evaluated using the SF-36 and PDQ-39 at
baseline and again after one year. In addition, their motor signs, motor
difficulties of daily living, and depressive symptoms were assessed as external
criteria. The internal responsiveness was examined using effect size,
standardized response mean, and the Wilcoxon signed rank test. The external
responsiveness was examined using receiver operating characteristic curves,
correlation analyses, and regression models. RESULTS: Both instruments were
partially sensitive to changes during the 1-year follow-up and able to
discriminate between patients with improved versus deteriorated motor signs. In
addition, both were similarly responsive to changes in the motor difficulties of
daily living; the SF-36 appeared to be more sensitive than the PDQ-39 to changes
in depressive symptoms. CONCLUSIONS: The SF-36 and the PDQ-39 were acceptably
internally and externally responsive during the 1-year follow-up.
PMID- 28420398
TI - Mechanisms of corticosteroid insensitivity in COPD alveolar macrophages exposed
to NTHi.
AB - BACKGROUND: Non-typeable Haemophilus influenza (NTHi) infection is common in
COPD. Corticosteroids can have limited therapeutic effects in COPD patients. NTHi
causes corticosteroid insensitive cytokine production from COPD alveolar
macrophages. We investigated the mechanisms by which NTHi causes corticosteroid
insensitive inflammatory responses, and the effects of NTHi exposure on COPD
macrophage polarisation. METHOD: Alveolar macrophages from COPD patients and
controls were exposed to NTHi in conjunction with the corticosteroid
dexamethasone and/or the p38 MAPK inhibitor BIRB-796. Cytokine release, GR
phosphorylation and modulation and macrophage phenotype were analysed. RESULTS:
Dexamethasone significantly inhibited NTHi induced TNF-alpha, IL-6 and IL-10 from
COPD macrophages but, CXCL8 was not suppressed. BIRB-796 combined with
dexamethasone caused significantly greater inhibition of all cytokines than
either drug alone (p < 0.05 all comparisons). NTHi caused phosphorylation of GR
S226 reducing GR nuclear localisation, an effect regulated by p38 MAPK. NTHi
altered macrophage polarisation by increasing IL-10 and decreasing CD36, CD206,
CD163 and HLA-DR. CONCLUSION: NTHi exposure causes p38 MAPK dependent GR
phosphorylation associated with decreased GR function in COPD alveolar
macrophages. Combining a p38 MAPK inhibitor with corticosteroids can enhance anti
inflammatory effects during NTHi exposure of COPD alveolar macrophages. NTHi
causes macrophage polarisation that favours bacterial persistence.
PMID- 28420399
TI - Distinct parasite populations infect individuals identified through passive and
active case detection in a region of declining malaria transmission in southern
Zambia.
AB - BACKGROUND: Substantial reductions in the burden of malaria have been documented
in parts of sub-Saharan Africa, with elimination strategies and goals being
formulated in some regions. Within this context, understanding the epidemiology
of low-level malaria transmission is crucial to achieving and sustaining
elimination. A 24 single-nucleotide-polymorphism Plasmodium falciparum molecular
barcode was used to characterize parasite populations from infected individuals
identified through passive and active case detection in an area approaching
malaria elimination in southern Zambia. METHODS: The study was conducted in the
catchment area of Macha Hospital in Choma District, Southern Province, Zambia,
where the parasite prevalence declined over the past decade, from 9.2% in 2008 to
less than 1% in 2013. Parasite haplotypes from actively detected, P. falciparum
infected participants enrolled in a serial cross-sectional, community-based
cohort study from 2008 to 2013 and from passively detected, P. falciparum
infected individuals enrolled at five rural health centres from 2012 to 2015 were
compared. Changes in P. falciparum genetic relatedness, diversity and complexity
were analysed as malaria transmission declined. RESULTS: Actively detected cases
identified in the community were most commonly rapid diagnostic test negative,
asymptomatic and had submicroscopic parasitaemia. Phylogenetic reconstruction
using concatenated 24 SNP barcode revealed a separation of parasite haplotypes
from passively and actively detected infections, consistent with two genetically
distinct parasite populations. For passively detected infections identified at
health centres, the proportion of detectable polyclonal infections was
consistently low in all seasons, in contrast with actively detected infections in
which the proportion of polyclonal infections was high. The mean genetic
divergence for passively detected infections was 34.5% for the 2012-2013
transmission season, 37.8% for the 2013-2014 season, and 30.8% for the 2014-2015
season. The mean genetic divergence for actively detected infections was 22.3% in
the 2008 season and 29.0% in the 2008-2009 season and 9.9% across the 2012-2014
seasons. CONCLUSIONS: Distinct parasite populations were identified among
infected individuals identified through active and passive surveillance,
suggesting that infected individuals detected through active surveillance may not
have contributed substantially to ongoing transmission. As parasite prevalence
and diversity within these individuals declined, resource-intensive efforts to
identify the chronically infected reservoir may not be necessary to eliminate
malaria in this setting.
PMID- 28420400
TI - Erratum to: New developments in anti-malarial target candidate and product
profiles.
PMID- 28420401
TI - Using media to impact health policy-making: an integrative systematic review.
AB - INTRODUCTION: Media interventions can potentially play a major role in
influencing health policies. This integrative systematic review aimed to assess
the effects of planned media interventions-including social media-on the health
policy-making process. METHODS: Eligible study designs included randomized and
non-randomized designs, economic studies, process evaluation studies, stakeholder
analyses, qualitative methods, and case studies. We electronically searched
Medline, EMBASE, Communication and Mass Media Complete, Cochrane Central Register
of Controlled Trials, and the WHO Global Health Library. We followed standard
systematic review methodology for study selection, data abstraction, and risk of
bias assessment. RESULTS: Twenty-one studies met our eligibility criteria: 10
evaluation studies using either quantitative (n = 7) or qualitative (n = 3)
designs and 11 case studies. None of the evaluation studies were on social media.
The findings of the evaluation studies suggest that media interventions may have
a positive impact when used as accountability tools leading to prioritizing and
initiating policy discussions, as tools to increase policymakers' awareness, as
tools to influence policy formulation, as awareness tools leading to policy
adoption, and as awareness tools to improve compliance with laws and regulations.
In one study, media-generated attention had a negative effect on policy advocacy
as it mobilized opponents who defeated the passage of the bills that the media
intervention advocated for. We judged the confidence in the available evidence as
limited due to the risk of bias in the included studies and the indirectness of
the evidence. CONCLUSION: There is currently a lack of reliable evidence to guide
decisions on the use of media interventions to influence health policy-making.
Additional and better-designed, conducted, and reported primary research is
needed to better understand the effects of media interventions, particularly
social media, on health policy-making processes, and the circumstances under
which media interventions are successful. TRIAL REGISTRATION: PROSPERO 2015:
CRD42015020243.
PMID- 28420402
TI - SSER: Species specific essential reactions database.
AB - BACKGROUND: Essential reactions are vital components of cellular networks. They
are the foundations of synthetic biology and are potential candidate targets for
antimetabolic drug design. Especially if a single reaction is catalyzed by
multiple enzymes, then inhibiting the reaction would be a better option than
targeting the enzymes or the corresponding enzyme-encoding gene. The existing
databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others
offer useful and comprehensive information on biochemical reactions. But none of
these databases especially focus on essential reactions. Therefore, building a
centralized repository for this class of reactions would be of great value.
DESCRIPTION: Here, we present a species-specific essential reactions database
(SSER). The current version comprises essential biochemical and transport
reactions of twenty-six organisms which are identified via flux balance analysis
(FBA) combined with manual curation on experimentally validated metabolic network
models. Quantitative data on the number of essential reactions, number of the
essential reactions associated with their respective enzyme-encoding genes and
shared essential reactions across organisms are the main contents of the
database. CONCLUSION: SSER would be a prime source to obtain essential reactions
data and related gene and metabolite information and it can significantly
facilitate the metabolic network models reconstruction and analysis, and drug
target discovery studies. Users can browse, search, compare and download the
essential reactions of organisms of their interest through the website
http://cefg.uestc.edu.cn/sser .
PMID- 28420403
TI - Molecular surveillance of Plasmodium falciparum drug resistance in the Republic
of Congo: four and nine years after the introduction of artemisinin-based
combination therapy.
AB - BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria
elimination and eradication. Following the global spread of chloroquine-resistant
parasites, the Republic of Congo adopted artemisinin-based combination therapy
(ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the
impacts after implementation of ACT, a molecular surveillance for anti-malarial
drug resistance was conducted in Congo 4 and 9 years after the introduction of
ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized
from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120). All
samples were screened for malaria parasites using nested PCR. Direct sequencing
was used to determine the frequency distribution of genetic variants in the anti
malarial drug-resistant Plasmodium falciparum genes (Pfcrt, Pfmdr1, Pfatp6,
Pfk13) in malaria-positive isolates. RESULTS: One-hundred and nineteen (N = 70
from 2010 and N = 49 from 2015) samples were positive for P. falciparum. A
relative decrease in the proportion of chloroquine-resistant haplotype (CVIET)
from 100% in 2005, 1 year before the introduction and implementation of ACT in
2006, to 98% in 2010 to 71% in 2015 was observed. Regarding the multidrug
transporter gene, a considerable reduction in the frequency of the mutations N86Y
(from 73 to 27%) and D1246Y (from 22 to 0%) was observed. However, the prevalence
of the Y184F mutation remained stable (49% in 2010 compared to 54% in 2015).
Isolates carrying the Pfatp6 H243Y was 25% in 2010 and this frequency was reduced
to null in 2015. None of the parasites harboured the Pfk13 mutations associated
with prolonged artemisinin clearance in Southeast Asia. Nevertheless, 13 new
Pfk13 variants are reported among the investigated isolates. CONCLUSION: The
implementation of ACT has led to the decline in prevalence of chloroquine
resistant parasites in the Republic of Congo. However, the constant prevalence of
the PfMDR1 Y184F mutation, associated with lumefantrine susceptibility, indicate
a selective drug pressure still exists. Taken together, this study could serve as
the basis for epidemiological studies monitoring the distribution of molecular
markers of artemisinin resistance in the Republic of Congo.
PMID- 28420404
TI - Development of a spatial sampling protocol using GIS to measure health
disparities in Bobo-Dioulasso, Burkina Faso, a medium-sized African city.
AB - BACKGROUND: Many cities in developing countries experience an unplanned and rapid
growth. Several studies have shown that the irregular urbanization and equipment
of cities produce different health risks and uneven exposure to specific
diseases. Consequently, health surveys within cities should be carried out at the
micro-local scale and sampling methods should try to capture this urban
diversity. METHODS: This article describes the methodology used to develop a
multi-stage sampling protocol to select a population for a demographic survey
that investigates health disparities in the medium-sized city of Bobo-Dioulasso,
Burkina Faso. It is based on the characterization of Bobo-Dioulasso city typology
by taking into account the city heterogeneity, as determined by analysis of the
built environment and of the distribution of urban infrastructures, such as
healthcare structures or even water fountains, by photo-interpretation of aerial
photographs and satellite images. Principal component analysis and hierarchical
ascendant classification were then used to generate the city typology. RESULTS:
Five groups of spaces with specific profiles were identified according to a set
of variables which could be considered as proxy indicators of health status.
Within these five groups, four sub-spaces were randomly selected for the study.
We were then able to survey 1045 households in all the selected sub-spaces. The
pertinence of this approach is discussed regarding to classical sampling as
random walk method for example. CONCLUSION: This urban space typology allowed to
select a population living in areas representative of the uneven urbanization
process, and to characterize its health status in regards to several indicators
(nutritional status, communicable and non-communicable diseases, and anaemia).
Although this method should be validated and compared with more established
methods, it appears as an alternative in developing countries where geographic
and population data are scarce.
PMID- 28420405
TI - Do International Health Partnerships contribute to reverse innovation? a mixed
methods study of THET-supported partnerships in the UK.
AB - BACKGROUND: International health partnerships (IHPs) are changing, with an
increased emphasis on mutual accountability and joint agenda setting for both the
high- and the low- or middle-income country (LMIC) partners. There is now an
important focus on the bi-directionality of learning however for the UK partners,
this typically focuses on learning at the individual level, through personal and
professional development. We sought to evaluate whether this learning also takes
the shape of 'Reverse Innovation' -when an idea conceived in a low-income country
is subsequently adopted in a higher-income country. METHODS: This mixed methods
study used an initial scoping survey of all the UK-leads of the Tropical Health
Education Trust (THET)-supported International Health Partnerships (n = 114) to
ascertain the extent to which the IHPs are or have been vehicles for Reverse
Innovation. The survey formed the sampling frame for further deep-dive interviews
to focus on volunteers' experiences and attitudes to learning from LMICs.
Interviews of IHP leads (n = 12) were audio-recorded and transcribed verbatim.
Survey data was analysed descriptively. Interview transcripts were coded
thematically, using an inductive approach. RESULTS: Survey response rate was 27%
(n = 34). The majority (70%) strongly agreed that supporting LMIC partners best
described the mission of the partnership but only 13% of respondents strongly
agreed that learning about new innovations and models was a primary mission of
their partnership. Although more than half of respondents reported having
observed innovative practice in the LMIC, only one IHP respondent indicated that
this has led to Reverse Innovation. Interviews with a sample of survey
respondents revealed themes primarily around how learning is conceptualised, but
also a central power imbalance between the UK and LMIC partners. Paternalistic
notions of knowledge could be traced to partnership power dynamics and latent
attitudes to LMICs. CONCLUSIONS: Given the global flow of innovation, if High
income countries (HICs) are to benefit from LMIC practices, it is paramount to
keep an open mind about where such learning can come from. Making the potential
for learning more explicit and facilitating innovation dissemination upon return
will ultimately underpin the success of adoption.
PMID- 28420406
TI - Genomics insights into different cellobiose hydrolysis activities in two
Trichoderma hamatum strains.
AB - BACKGROUND: Efficient biomass bioconversion is a promising solution to
alternative energy resources and environmental issues associated with
lignocellulosic wastes. The Trichoderma species of cellulolytic fungi have strong
cellulose-degrading capability, and their cellulase systems have been extensively
studied. Currently, a major limitation of Trichoderma strains is their low
production of beta-glucosidases. RESULTS: We isolated two Trichoderma hamatum
strains YYH13 and YYH16 with drastically different cellulose degrading
efficiencies. YYH13 has higher cellobiose-hydrolyzing efficiency. To understand
mechanisms underlying such differences, we sequenced the genomes of YYH13 and
YYH16, which are essentially identical (38.93 and 38.92 Mb, respectively) and are
similar to that of the T. hamatum strain GD12. Using GeneMark-ES, we annotated
11,316 and 11,755 protein-coding genes in YYH13 and YYH16, respectively.
Comparative analysis identified 13 functionally important genes in YYH13 under
positive selection. Through examining orthologous relationships, we identified
172,655, and 320 genome-specific genes in YYH13, YYH16, and GD12, respectively.
We found 15 protease families that show differences between YYH13 and YYH16.
Enzymatic tests showed that exoglucanase, endoglucanase, and beta-glucosidase
activities were higher in YYH13 than YYH16. Additionally, YYH13 contains 10
families of carbohydrate-active enzymes, including GH1, GH3, GH18, GH35, and GH55
families of chitinases, glucosidases, galactosidases, and glucanases, which are
subject to stronger positive selection pressure. Furthermore, we found that the
beta-glucosidase gene (YYH1311079) and pGEX-KG/YYH1311079 bacterial expression
vector may provide valuable insight for designing beta-glucosidase with higher
cellobiose-hydrolyzing efficiencies. CONCLUSIONS: This study suggests that the
YYH13 strain of T. hamatum has the potential to serve as a model organism for
producing cellulase because of its strong ability to efficiently degrade
cellulosic biomass. The genome sequences of YYH13 and YYH16 represents a valuable
resource for studying efficient production of biofuels.
PMID- 28420407
TI - Understanding Phlebotomus perniciosus abundance in south-east Spain: assessing
the role of environmental and anthropic factors.
AB - BACKGROUND: Leishmaniosis is associated with Phlebotomus sand fly vector density,
but our knowledge of the environmental framework that regulates highly
overdispersed vector abundance distributions is limited. We used a standardized
sampling procedure in the bioclimatically diverse Murcia Region in Spain and
multilevel regression models for count data to estimate P. perniciosus abundance
in relation to environmental and anthropic factors. METHODS: Twenty-five dog and
sheep premises were sampled for sand flies using adhesive and light-attraction
traps, from late May to early October 2015. Temperature, relative humidity and
other animal- and premise-related data recorded on site and other environmental
data were extracted from digital databases using a geographical information
system. The relationship between sand fly abundance and explanatory variables was
analysed using binomial regression models. RESULTS: The total number of sand
flies captured, mostly with light-attraction traps, was 3,644 specimens,
including 80% P. perniciosus, the main L. infantum vector in Spain. Abundance
varied between and within zones and was positively associated with increasing
altitude from 0 to 900 m above sea level, except from 500 to 700 m where it was
low. Populations peaked in July and especially during a 3-day heat wave when
relative humidity and wind speed plummeted. Regression models indicated that
climate and not land use or soil characteristics have the greatest impact on this
species density on a large geographical scale. In contrast, micro-environmental
factors such as animal building characteristics and husbandry practices affect
sand fly population size on a smaller scale. CONCLUSIONS: A standardised sampling
procedure and statistical analysis for highly overdispersed distributions allow
reliable estimation of P. perniciosus abundance and identification of
environmental drivers. While climatic variables have the greatest impact at macro
environmental scale, anthropic factors may be determinant at a micro-geographical
scale. These finding may be used to elaborate predictive distribution maps useful
for vector and pathogen control programs.
PMID- 28420408
TI - Sialylation regulates myofibroblast differentiation of human skin fibroblasts.
AB - BACKGROUND: Fibroblasts are key players in maintaining skin homeostasis and in
orchestrating physiological tissue repair and skin regeneration. Dysfunctions in
fibroblasts that occur with aging and the senescent process lead to the delayed
healing observed in elderly people. The molecular mechanisms leading to
fibroblast dysfunction during aging and the senescent process have not yet been
clarified. Previously, changes in patterns of glycosylation were observed in
fibroblasts in aging and the senescent process, but the effect of these changes
on the function of fibroblasts has not been well documented. Here, we
investigated whether changes in glycosylation during the process to senescence
may have functional effects on fibroblasts. METHODS: The changes in cell surface
glycans on skin fibroblasts during the process to senescence were examined in
early-passage (EP) and late-passage (LP) skin fibroblasts by fluorescence
activated cell sorting analysis using lectins. The contributors to the changes in
cell surface glycans were examined by real-time polymerase chain reaction or
Western blot analysis. The effects of changes in glycosylation on proliferation,
migration, induction of cellular senescence, and myofibroblast differentiation
induced by transforming growth factor (TGF)-beta1 stimulation were examined in EP
fibroblasts. The changes in glycosylation were performed by GalNAc-alpha-O-benzyl
or sialidase treatment. RESULTS: A decrease in sialylation of glycoproteins and
an increase in sialidase NEU1 were observed in LP fibroblasts. The reduction of
sialylation did not have any effect on proliferation, migration, or induction of
cellular senescence. On the other hand, myofibroblast differentiation was
inhibited by the reduction of sialylation, indicating that sialylation is
important for myofibroblast differentiation. The localization of CD44 in lipid
rafts, which is required for myofibroblast differentiation, was inhibited by the
reduction of sialylation. Furthermore, reduced myofibroblast differentiation in
LP fibroblasts was restored by a sialidase inhibitor. CONCLUSIONS: Desialylation
of CD44 with increased sialidase during the process to senescence reduced the
localization of CD44 in lipid rafts after TGF-beta1 stimulation, leading to the
inhibition of myofibroblast differentiation. Thus, regulation of sialylation may
be an attractive strategy for the prevention and regenerative therapy of age
related skin diseases, cosmetic skin alterations, and chronic wounds caused by
delayed healing in elderly people.
PMID- 28420409
TI - Assessing the status of iodine deficiency disorder (IDD) and associated factors
in Wolaita and Dawro Zones School Adolescents, southern Ethiopia.
AB - BACKGROUND: Iodine deficiency is the major preventable cause of irreversible
mental retardation in the world. Ethiopia is a country with high prevalence of
iodine deficiency disorders which continue to affect a large number of the
country's population. The aim of the study was to assess the prevalence of iodine
deficiency disorder in Wolaita and Dawuro zones. METHODS: A descriptive, cross
sectional study was conducted in high school and preparatory students in Wolaita
and Dawuro zones between April and May 2012. Data were collected from 718 school
adolescents using pre-tested questionnaire through systematic random sampling
technique. Data were entered and cleaned using Epi-info version 3.5.3 and then
transported to SPSS version 20 for analysis. Bivariate and Multivariable logistic
regression were done and the cut off value set was P < 0.05 as this is considered
as statistically significant. RESULT: The overall prevalence (total goiter rate)
of goiter in study area was 351 (48.9%). Students with Grade-1 goiter were 265
(36.9%) while with Grade-2 goiter was 86 (11.9%). Females were by a long way
vulnerable for goiter and accounts 60.9% with Pearson correlation coefficient
0.300, P value 0.0001. Generally, the occurrence of goiter in the study area was
found to have statistical significant association with sex of respondents (being
female) [AOR = 3.526; 95% CI (2.55-4.87)], climatic condition of resident
(temperate climate) [AOR = 0.617; 95% CI (0.404-0.943)], frequency of iodized
salt use [AOR = 0.484; 95% CI (0.317-0.739)] and consumption of cassava [AOR =
4.184; 95% CI (2.6-6.707)]. CONCLUSION AND RECOMMENDATION: In general, the study
revealed that iodine deficiency disorder was a serious public health concern.
Nearly half of adolescent students in Wolaita and Dawuro zones were affected by
goiter. Therefore, emphasis on a sustainable iodine intervention program targeted
at population level, particularly at females is mandatory. Nutrition education
along with adequate Universal Salt Iodization program is urgently required.
PMID- 28420410
TI - Ethnopharmacologic survey of medicinal plants used to treat human diseases by
traditional medical practitioners in Dega Damot district, Amhara, Northwestern
Ethiopia.
AB - BACKGROUND: One of the services that plants provide for human beings is their
wider medicinal application. Although it is not fully assessed, the practice and
wider use of traditional medicine is frequent in Ethiopia. Studies conducted
previously are confined to the perceptions of modern and traditional health
practitioners about traditional medicine. A total of 45 informants were selected
purposefully from the study area. For collecting the data, semi-structured
interviewees, observation and field walks were employed from August 10 to
September 30/2014. To summarize the information, descriptive statistical methods
were applied. RESULTS: Sixty species of medicinal plants distributed in 42
families were collected and identified applied locally for the treatment of 55
human disorders. The most commonly treated ones were evil eye, malaria, wound,
peptic ulcer disease and rabies. According to this study, leaves were the
commonly used plant parts (36.5%) and 39% of the preparations were decoctions.
Oral route, 43 (44%) was the commonly used route of application whereas most
(54.8%) remedies were administered only once. Fourteen percent of preparations
caused vomiting in addition most (40.4%) of the formulations was contraindicated
for pregnant patients. Only seventeen percent of the formulations possessed drug
food interactions. Most preparations were stored within clothes, 31 (29.8%).
There exists a high (ICF = 0.8) evenness of plant use among healers for treating
respiratory problems. Alliumsativum (FI = 0.75) for evil eye, Phytolacca
dodecandra (FI = 0.8) for rabies and Croton macrostachyus (FI = 0.78) for
treating malaria were medicinal plants with highest fidelity levels showing
consistency of knowledge on species best treating power. This study also
documented that drought, overgrazing and firewood collection are major threats.
CONCLUSION: Dega Damot district is loaded in its medicinal plant diversity and
indigenous knowledge though plants are highly affected by drought, overgrazing
and firewood collection. Therefore awareness activities must be created among the
district's population by concerned governmental and nongovernmental organizations
about the value of medicinal plants and conservation of these plants. The healing
potential and associated adverse issues of the claimed medicinal plants should be
assessed before proposing for a broader utilization.
PMID- 28420411
TI - Characterization of a novel aspartyl protease inhibitor from Haemonchus
contortus.
AB - BACKGROUND: Aspartyl protease inhibitor (API) was thought to protect intestinal
parasitic nematodes from their hostile proteolytic environment. Studies on
Ostertagia ostertagi, Ascaris suum and Brugia malayi indicated that aspins might
play roles in nematode infection. In a recent study, proteins differentially
expressed between free-living third-stage larvae (L3) and activated L3 (xL3) of
Haemonchus contortus were identified by 2D-DIGE. API was found downregulated in
xL3 when compared with L3. However, there was no report about the functions of H.
contortus API in the parasite-host interaction. In this study, the gene encoding
API from H. contortus was cloned, expressed, and part of its biological
characteristics were studied. RESULTS: A DNA fragment of 681 bp was amplified by
RT-PCR. Ninety one percent of the amino acid sequence was similar with that for
aspin from O. ostertagi. The recombinant API protein was fusion-expressed with a
molecular weight of 48 * 103. Results of Western blot showed that the recombinant
API could be recognized by serum from goat infected with H. contortus. It was
found that API was localized exclusively in the subcutaneous tissue and
epithelial cells of the gastrointestinal tract in adult H. contortus. qRT-PCR
suggested that the API gene was differentially transcribed in different life
cycle stages, with the lowest level in female adults and the highest in free
living L3 larvae. Enzyme inhibition assay indicated that the recombinant API can
inhibit the activity of pepsin significantly, and the optimal reaction pH and
temperature were 4.0 and 37-50 degrees C respectively. In vitro study showed
that the recombinant API could induce goat PBMCs to express IFN-gamma, IL-4 and
IL-10. CONCLUSIONS: A new aspartyl protease inhibitor was cloned from H.
contortus and its characteristics were studied for the first time. The results
indicate that API may regulate the immune response of the host and play roles in
the infection.
PMID- 28420412
TI - Intersect-then-combine approach: improving the performance of somatic variant
calling in whole exome sequencing data using multiple aligners and callers.
AB - Bioinformatic analysis of genomic sequencing data to identify somatic mutations
in cancer samples is far from achieving the required robustness and
standardisation. In this study we generated a whole exome sequencing benchmark
dataset using the platinum genome sample NA12878 and developed an intersect-then
combine (ITC) approach to increase the accuracy in calling single nucleotide
variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of
alignment, base quality recalibration, mutation caller and filtering on
sensitivity and false positive rate. The ITC approach increased the sensitivity
up to 17.1%, without increasing the false positive rate per megabase (FPR/Mb) and
its validity was confirmed in a set of clinical samples.
PMID- 28420413
TI - Is combined use of intravenous and intraarticular tranexamic acid superior to
intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A
meta-analysis of randomized controlled trials.
AB - BACKGROUND: Tranexamic acid (TXA) has been proven to be effective in reducing
blood loss and transfusion rate after total knee arthroplasty (TKA) without
increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).
Recently, an increasing number of studies have been interested in applying
combined intravenous (IV) with intraarticular (IA) tranexamic acid in total knee
arthroplasty. The purpose of this meta-analysis was to compare the blood loss and
complications of combined TXA with IV TXA or IA TXA on TKA. METHODS: Systematic
search of literatures were conducted to identify related articles that were
published in PubMed, MEDLINE, Embase, the Cochrane Library, SpringerLink,
ClinicalTrials.gov, and Ovid from their inception to September 2016. All studies
that compare blood loss and complications of combined TXA and IV TXA or IA TXA on
TKA were included. Main outcomes were collected and analyzed by the Review
Manager 5.3. RESULTS: Five studies were included in the present meta-analysis.
There was significant difference in total blood loss and blood volume of drainage
when compared combined TXA group with IV TXA group or IA TXA group (P < 0.05).
There was no difference in transfusion rate and thromboembolic complications when
comparing combined TXA with IV TXA or IA TXA alone (P > 0.05). CONCLUSIONS:
Compared with administration of IA TXA or IV TXA alone on TKA, combined use of
TXA has advantages in reducing total blood loss and blood volume of drainage
without increasing the incidence of thromboembolic complications. We recommend
combined TXA as the preferred option for patients undergoing TKA.
PMID- 28420414
TI - Integrated genomic analysis of mitochondrial RNA processing in human cancers.
AB - BACKGROUND: The mitochondrial genome is transcribed as continuous polycistrons of
RNA containing multiple genes. As a consequence, post-transcriptional events are
critical for the regulation of gene expression and therefore all aspects of
mitochondrial function. One particularly important process is the m1A/m1G RNA
methylation of the ninth position of different mitochondrial tRNAs, which allows
efficient processing of mitochondrial mRNAs and protein translation, and de
regulation of genes involved in these processes has been associated with altered
mitochondrial function. Although mitochondria play a key role in cancer, the
status of mitochondrial RNA processing in tumorigenesis is unknown. METHODS: We
measure and assess mitochondrial RNA processing using integrated genomic analysis
of RNA sequencing and genotyping data from 1226 samples across 12 different
cancer types. We focus on the levels of m1A and m1G RNA methylation in
mitochondrial tRNAs in normal and tumor samples and use supervised and
unsupervised statistical analysis to compare the levels of these modifications to
patient whole genome genotypes, nuclear gene expression, and survival outcomes.
RESULTS: We find significant changes to m1A and m1G RNA methylation levels in
mitochondrial tRNAs in tumor tissues across all cancers. Pathways of RNA
processing are strongly associated with methylation levels in normal tissues (P =
3.27 * 10-31), yet these associations are lost in tumors. Furthermore, we report
18 gene-by-disease-state interactions where altered RNA methylation levels occur
under cancer status conditional on genotype, implicating genes associated with
mitochondrial function or cancer (e.g., CACNA2D2, LMO2, and FLT3) and suggesting
that nuclear genetic variation can potentially modulate an individual's ability
to maintain unaltered rates of mitochondrial RNA processing under cancer status.
Finally, we report a significant association between the magnitude of methylation
level changes in tumors and patient survival outcomes. CONCLUSIONS: We report
widespread variation of mitochondrial RNA processing between normal and tumor
tissues across all cancer types investigated and show that these alterations are
likely modulated by patient genotype and may impact patient survival outcomes.
These results highlight the potential clinical relevance of altered mitochondrial
RNA processing and provide broad new insights into the importance and complexity
of these events in cancer.
PMID- 28420415
TI - Distribution pattern following systemic mesenchymal stem cell injection depends
on the age of the recipient and neuronal health.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) show therapeutic efficacy in many
different age-related degenerative diseases, including Alzheimer's disease. Very
little is currently known about whether or not aging impacts the transplantation
efficiency of MSCs. METHODS: In this study, we investigated the distribution of
intravenously transplanted syngeneic MSCs derived from young and aged mice into
young, aged, and transgenic APP/PS1 Alzheimer's disease mice. MSCs from male
donors were transplanted into female mice and their distribution pattern was
monitored by PCR using Y-chromosome specific probes. Biodistribution of
transplanted MSCs in the brains of APP/PS1 mice was additionally confirmed by
immunofluorescence and confocal microscopy. RESULTS: Four weeks after
transplantation into young mice, young MSCs were found in the lung, axillary
lymph nodes, blood, kidney, bone marrow, spleen, liver, heart, and brain cortex.
In contrast, young MSCs that were transplanted into aged mice were only found in
the brain cortex. In both young and aged mouse recipients, transplantation of
aged MSCs showed biodistribution only in the blood and spleen. Although young
transplanted MSCs only showed neuronal distribution in the brain cortex in young
mice, they exhibited a wide neuronal distribution pattern in the brains of
APP/PS1 mice and were found in the cortex, cerebellum, hippocampus, olfactory
bulb, and brainstem. The immunofluorescent signal of both transplanted MSCs and
resident microglia was robust in the brains of APP/PS1 mice. Monocyte
chemoattractant-1 levels were lowest in the brain cortex of young mice and were
significantly increased in APP/PS1 mice. Within the hippocampus, monocyte
chemoattractant-1 levels were significantly higher in aged mice compared with
younger and APP/PS1 mice. CONCLUSIONS: We demonstrate in vivo that MSC
biodistribution post transplantation is detrimentally affected by aging and
neuronal health. Aging of both the recipient and the donor MSCs used attenuates
transplantation efficiency. Clinically, our data would suggest that aged MSCs
should not be used for transplantation and that transplantation of MSCs into aged
patients will be less efficacious.
PMID- 28420416
TI - Emerging therapies for acute myeloid leukemia.
AB - Acute myeloid leukemia (AML) is characterized by clinical and biological
heterogeneity. Despite the advances in our understanding of its pathobiology, the
chemotherapy-directed management has remained largely unchanged in the past 40
years. However, various novel agents have demonstrated clinical activity, either
as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab)
or in combination with standard induction/consolidation at diagnosis and with
salvage regimens at relapse. The classes of agents described in this review
include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic
modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors,
bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase
receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as
well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors,
and aminopeptidase inhibitors. These agents are actively undergoing clinical
investigation alone or in combination with available chemotherapy.
PMID- 28420417
TI - Do images of a personalised future body shape help with weight loss? A randomised
controlled study.
AB - BACKGROUND: This randomised controlled study evaluated a computer-generated
future self-image as a personalised, visual motivational tool for weight loss in
adults. METHODS: One hundred and forty-five people (age 18-79 years) with a Body
Mass Index (BMI) of at least 25 kg/m2 were randomised to receive a hard copy
future self-image at recruitment (early image) or after 8 weeks (delayed image).
Participants received general healthy lifestyle information at recruitment and
were weighed at 4-weekly intervals for 24 weeks. The image was created using an
iPad app called 'Future Me'. A second randomisation at 16 weeks allocated either
an additional future self-image or no additional image. RESULTS: Seventy-four
participants were allocated to receive their image at commencement, and 71 to the
delayed-image group. Regarding to weight loss, the delayed-image group did
consistently better in all analyses. Twenty-four recruits were deemed non
starters, comprising 15 (21%) in the delayed-image group and 9 (12%) in the early
image group (chi2(1) = 2.1, p = 0.15). At 24 weeks there was a significant change
in weight overall (p < 0.0001), and a difference in rate of change between groups
(delayed-image group: -0.60 kg, early-image group: -0.42 kg, p = 0.01). Men lost
weight faster than women. The group into which participants were allocated at
week 16 (second image or not) appeared not to influence the outcome (p = 0.31).
Analysis of all completers and withdrawals showed a strong trend over time (p <
0.0001), and a difference in rate of change between groups (delayed-image: -0.50
kg, early-image: -0.27 kg, p = 0.0008). CONCLUSION: One in five participants in
the delayed-image group completing the 24-week intervention achieved a clinically
significant weight loss, having received only future self-images and general
lifestyle advice. Timing the provision of future self-images appears to be
significant, and promising for future research to clarify their efficacy. TRIAL
REGISTRATION: Australian Clinical Trials Registry, identifier:
ACTRN12613000883718 . Registered on 8 August 2013.
PMID- 28420418
TI - Adult muscle-derived stem cells engraft and differentiate into insulin-expressing
cells in pancreatic islets of diabetic mice.
AB - BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose
homeostasis and their deficiency results in impaired insulin production leading
to severe diabetic diseases. Here, we investigated the potential of a population
of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to
differentiate in vitro into beta cells when transplanted as undifferentiated stem
cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured
MDSC spontaneously differentiated into insulin-expressing islet-like cell
clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry
under the control of an insulin promoter. Differentiated clusters of beta-like
cells co-expressed insulin with the transcription factors Pdx1, Nkx2.2, Nkx6.1,
and MafA, and secreted significant levels of insulin in response to glucose
challenges. In vivo, undifferentiated MDSC injected into streptozotocin (STZ)
treated mice engrafted within 48 h specifically to damaged pancreatic islets and
were shown to differentiate and express insulin 10-12 days after injection. In
addition, injection of MDSC into hyperglycemic diabetic mice reduced their blood
glucose levels for 2-4 weeks. CONCLUSION: These data show that MDSC are capable
of differentiating into mature pancreatic beta islet-like cells, not only upon
culture in vitro, but also in vivo after systemic injection in STZ-induced
diabetic mouse models. Being nonteratogenic, MDSC can be used directly by
systemic injection, and this potential reveals a promising alternative avenue in
stem cell-based treatment of beta-cell deficiencies.
PMID- 28420419
TI - Optimizing veteran-centered prostate cancer survivorship care: study protocol for
a randomized controlled trial.
AB - BACKGROUND: Although prostate cancer is the most common cancer among veterans
receiving care in the Veterans Health Administration (VA), more needs to be done
to understand and improve survivorship care for this large population. This
study, funded by VA Health Services Research & Development (HSR&D), seeks to
address the need to improve patient-centered survivorship care for veterans with
prostate cancer. METHODS/DESIGN: This is a two-armed randomized controlled trial
(RCT) with a target enrollment of up to 325 prostate cancer survivors per study
arm (total anticipated n = 600). Patients will be recruited from four VA sites.
Patient eligibility criteria include age range of 40-80 years, one to ten years
post-treatment, and currently experiencing prostate cancer symptom burden. We
will compare the "Building Your New Normal" program, a personally-tailored
automated telephone symptom management intervention for improving symptom self
management to usual care enhanced with a non-tailored newsletter about symptom
management. Primary outcomes include changes in symptom burden, bother, and
health services utilization at five and 12 months after enrollment. Secondary
outcomes include long-term psychosocial outcomes (e.g. subjective health,
perceived cancer control). We will use multivariable regression analysis to
evaluate the impact of the intervention on primary and secondary outcomes. We
will conduct a process evaluation to understand the effective intervention
components and explore possibilities for broader implementation and
dissemination. DISCUSSION: Our central hypothesis is that intervention group
participants will have improved and more confident symptom self-management and
prostate cancer quality of life following the intervention and that these
outcomes will translate to more efficient use of health services. The study
results will provide much needed information about how to optimize the quality of
care, and life, of veteran prostate cancer survivors. TRIAL REGISTRATION:
ClinicalTrials.gov ID NCT01900561 ; Registered on 22 July 2013.
PMID- 28420420
TI - Distribution of ticks infesting ruminants and risk factors associated with high
tick prevalence in livestock farms in the semi-arid and arid agro-ecological
zones of Pakistan.
AB - BACKGROUND: Tick infestation is the major problem for animal health that causes
substantial economic losses, particularly in tropical and subtropical countries.
To better understand the spatial distribution of tick species and risk factors
associated with tick prevalence in livestock in Pakistan, ticks were counted and
collected from 471 animals, including 179 cattle, 194 buffaloes, 80 goats and 18
sheep, on 108 livestock farms in nine districts, covering both semi-arid and arid
agro-ecological zones. RESULTS: In total, 3,807 ticks representing four species
were collected: Hyalomma anatolicum (n = 3,021), Rhipicephalus microplus (n =
715), Hyalomma dromedarii (n = 41) and Rhipicephalus turanicus (n = 30). The
latter species is reported for the first time from the study area. Rhipicephalus
microplus was the predominant species in the semi-arid zone, whereas H.
anatolicum was the most abundant species in the arid zone. The overall proportion
of tick-infested ruminants was 78.3% (369/471). It was highest in cattle (89.9%),
followed by buffaloes (81.4%), goats (60.0%) and sheep (11.1%). The median tick
burden significantly differed among animal species and was highest in cattle
(median 58), followed by buffaloes (median 38), goats (median 19) and sheep
(median 4.5). Female animals had significantly higher tick burdens than males
and, in large ruminants, older animals carried more ticks than younger animals.
The intensity of infestation was significantly lower in indigenous animals
compared to exotic and crossbred cows. Analysis of questionnaire data revealed
that the absence of rural poultry, not using any acaricides, traditional rural
housing systems and grazing were potential risk factors associated with a higher
tick prevalence in livestock farms. CONCLUSION: Absence of rural poultry, not
performing acaricide treatments, traditional rural housing systems and grazing
were important risk factors associated with higher tick prevalence in livestock
farms. Age, gender, breed and animal species significantly affected the intensity
of tick infestation. This report also describes the presence of R. turanicus in
the Punjab Province of Pakistan for the first time. The outcomes of this study
will be useful in the planning of integrated control strategies for ticks and
tick-borne diseases in Pakistan.
PMID- 28420421
TI - Analysis of 100,000 human cancer genomes reveals the landscape of tumor
mutational burden.
AB - BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of
sensitivity to immune checkpoint inhibitors and has been shown to be more
significantly associated with response to PD-1 and PD-L1 blockade immunotherapy
than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The
distribution of TMB and the subset of patients with high TMB has not been well
characterized in the majority of cancer types. METHODS: In this study, we compare
TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB
measured by exome sequencing and simulate the expected variance in TMB when
sequencing less than the whole exome. We then describe the distribution of TMB
across a diverse cohort of 100,000 cancer cases and test for association between
somatic alterations and TMB in over 100 tumor types. RESULTS: We demonstrate that
measurements of TMB from comprehensive genomic profiling are strongly reflective
of measurements from whole exome sequencing and model that below 0.5 Mb the
variance in measurement increases significantly. We find that a subset of
patients exhibits high TMB across almost all types of cancer, including many rare
tumor types, and characterize the relationship between high TMB and
microsatellite instability status. We find that TMB increases significantly with
age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we
investigate the molecular basis of TMB and identify genes and mutations
associated with TMB level. We identify a cluster of somatic mutations in the
promoter of the gene PMS2, which occur in 10% of skin cancers and are highly
associated with increased TMB. CONCLUSIONS: These results show that a CGP assay
targeting ~1.1 Mb of coding genome can accurately assess TMB compared with
sequencing the whole exome. Using this method, we find that many disease types
have a substantial portion of patients with high TMB who might benefit from
immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2,
which may be another example of regulatory mutations contributing to
tumorigenesis.
PMID- 28420422
TI - High resolution melting: a useful field-deployable method to measure dhfr and
dhps drug resistance in both highly and lowly endemic Plasmodium populations.
AB - BACKGROUND: Emergence and spread of drug resistance to every anti-malarial used
to date, creates an urgent need for development of sensitive, specific and field
deployable molecular tools for detection and surveillance of validated drug
resistance markers. Such tools would allow early detection of mutations in
resistance loci. The aim of this study was to compare common population
signatures and drug resistance marker frequencies between two populations with
different levels of malaria endemicity and history of anti-malarial drug use:
Tanzania and Senegal. This was accomplished by implementing a high resolution
melting assay to study molecular markers of drug resistance as compared to
polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP)
methodology. METHODS: Fifty blood samples were collected each from a lowly
malaria endemic site (Senegal), and a highly malaria endemic site (Tanzania) from
patients presenting with uncomplicated Plasmodium falciparum malaria at clinic.
Data representing the DHFR were derived using both PCR-RFLP and HRM assay; while
genotyping data representing the DHPS were evaluated in Senegal and Tanzania
using HRM. Msp genotyping analysis was used to characterize the multiplicity of
infection in both countries. RESULTS: A high prevalence of samples harbouring
mutant DHFR alleles was observed in both population using both genotyping
techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for
DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from
Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and
DHPS (codon 437) were found among samples from Senegal while no mutations were
observed at DHPS codons 540 and 581, from both countries. Overall, the frequency
of samples harbouring either a single DHFR mutation (S108N) or double mutation in
DHFR (C59R/S108N) was greater in Senegal compared to Tanzania. CONCLUSION: Here
the results demonstrate that HRM is a rapid, sensitive, and field-deployable
alternative technique to PCR-RFLP genotyping that is useful in populations
harbouring more than one parasite genome (polygenomic infections). In this study,
a high levels of resistance polymorphisms was observed in both dhfr and dhps,
among samples from Tanzania and Senegal. A routine monitoring by molecular
markers can be a way to detect emergence of resistance involving a change in the
treatment policy.
PMID- 28420423
TI - A comprehensive evaluation of an ELISA for the diagnosis of the two most common
ascarids in chickens using plasma or egg yolks.
AB - BACKGROUND: Classical faecal egg counts (FEC) provide less reliable diagnostic
information for nematode infections in chickens. We developed an ELISA based on
Ascaridia galli antigens and tested two hypotheses, as follows: (i) IgY
antibodies developed against A. galli will also be useful to identify Heterakis
gallinarum infections, and (ii) circulating antibodies stored in egg yolks are as
good as plasma samples, so a non-invasive diagnosis is possible. The aim of this
study, therefore, was to compare the diagnostic accuracy of the ELISA system with
FEC, using both plasma and egg yolks from experimentally infected hens. In
addition, naturally infected animals were evaluated to validate the assay.
RESULTS: The assay quantified large differences (P < 0.001) in plasma or in egg
yolk IgY concentrations between infected and uninfected animals in two
experiments, each performed with either of the nematode species. The assay
performed with high accuracy as quantified with the area under the ROC curve
(AUC) values of > 0.90 for both nematodes using either plasma or egg yolks.
Sensitivity of the assay was 94 and 93% with plasma and egg yolk samples,
respectively, whereas FEC yielded in a sensitivity of 84% in A. galli experiment.
Total test accuracy of the assay with plasma samples (AUC = 0.99) tended to be
higher (P = 0.0630) than FEC (AUC = 0.92) for A. galli, while the assay with
either sample matrix performed similar to FEC (AUC >= 0.91) for H. gallinarum.
Among the three tests, the FECs correlated better with A. galli burden than the
ELISA. Although 90% of naturally infected hens were correctly identified by the
ELISA, 45% of the infected hens tested negative with FEC, indicating the validity
of the higher test accuracy of the ELISA. CONCLUSIONS: Antigens of A. galli can
be used successfully to identify H. gallinarum-infected animals, indicating that
chickens develop cross-reactive antibodies against the two closely related
species. Egg yolks are as informative as plasma samples, so that animal welfare
friendly sampling is possible. Although the assay with plasma samples reveals
qualitative information of higher quality than FECs on the infection status of
naturally infected birds, the latter is still a better tool to assess the
intensity of A. galli but not of H. gallinarum infections.
PMID- 28420424
TI - A novel lncRNA uc.134 represses hepatocellular carcinoma progression by
inhibiting CUL4A-mediated ubiquitination of LATS1.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies
worldwide, and tumor recurrence and metastasis are major factors that contribute
to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known
to regulate different tumorigenic processes, and a growing body of evidence
indicates that Hippo kinase signaling is inactivated in many cancers. However,
the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly
understood. METHODS: Using a lncRNA microarray, we identified a novel lncRNA,
uc.134, whose expression was significantly decreased in the highly aggressive HCC
cell line HCCLM3 compared with MHCC97L cells. Furthermore, we evaluated uc.134
expression in clinical samples using in situ hybridization (ISH) and quantitative
real-time polymerase chain reaction (qRT-PCR) analysis. The full-length
transcript of uc.134 was confirmed using rapid amplification of cDNA ends (RACE)
analyses. To investigate the biological function of uc.134, we performed gain-of
function and loss-of-function studies both in vitro and in vivo. The underlying
mechanisms of uc.134 in HCC were investigated using RNA pulldown, RNA
immunoprecipitation, ubiquitination assays, Western blotting, mRNA microarray
analyses, and qRT-PCR analyses. RESULTS: The ISH assay revealed that uc.134
expression was significantly decreased in 170 paraffin-embedded samples from
patients with HCC compared with adjacent tissues and uc.134 expression directly
correlated with patient prognosis. Furthermore, we defined a 1867-bp full-length
transcript of uc.134 using 5'- and 3'-RACE analysis. The overexpression of uc.134
inhibited HCC cell proliferation, invasion, and metastasis in vitro and in vivo,
whereas the knockdown of uc.134 produced the opposite results. Furthermore, we
confirmed that uc.134 (1408-1867 nt) binds to CUL4A (592-759 aa region) and
inhibits its nuclear export. Moreover, we demonstrated that uc.134 inhibits the
CUL4A-mediated ubiquitination of LATS1 and increases YAPS127 phosphorylation to
silence the target genes of YAP. Finally, a positive correlation between uc.134,
LATS1, and pYAPS127 was confirmed in 90 paraffin-embedded samples by ISH and
immunohistochemical staining. CONCLUSIONS: Our study identifies that a novel
lncRNA, uc.134, represses hepatocellular carcinoma progression by inhibiting the
CUL4A-mediated ubiquitination of LATS1 and increasing YAPS127 phosphorylation.
The use of this lncRNA may offer a promising treatment approach by inhibiting YAP
and activating Hippo kinase signaling.
PMID- 28420425
TI - Acceleration of tendon-bone healing of anterior cruciate ligament graft using
intermittent negative pressure in rabbits.
AB - BACKGROUND: The purpose of this study was to test effects of negative pressure on
tendon-bone healing after reconstruction of anterior cruciate ligament (ACL) in
rabbits. METHODS: Hind legs of 24 New Zealand White rabbits were randomly
selected as negative pressure group and the contralateral hind legs as control.
Reconstruction of the ACL was done. Joints of the negative pressure side were
placed with drainage tubes connecting the micro-negative pressure aspirator.
Control side was placed with ordinary drainage tubes. Drainage tubes on both
sides were removed at the same time 5 days after operation. After 6 weeks, joint
fluid was drawn to detect the expression levels of interleukin-1beta (IL-1beta)
and tumor necrosis factor-alpha (TNF-alpha); at the same time, femur-ligament
tibia complex was obtained to determine tendon graft tension and to observe the
histomorphology, blood vessels of the tendon-bone interface, and expression of
vascular endothelial growth factor (VEGF). RESULTS: The maximum load breakage of
tendon graft was significantly greater in the negative pressure group than in the
control group (P < 0.05). Histological studies of the tendon-bone interface found
that there was more new bone formation containing chondroid cells and aligned
connective tissue in the negative pressure group than in the control group.
Expression of VEGF was higher in the negative pressure group than in the control
group (P < 0.01). Content of IL-1beta and TNF-alpha in synovial fluid is lower in
the negative pressure group than in the control group (P < 0.01). CONCLUSIONS:
Intermittent negative pressure plays an active role in tendon-bone healing and
creeping substitution of ACL reconstruction in the rabbits.
PMID- 28420426
TI - Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response
of chronic myeloid leukemia patients to imatinib treatment.
AB - BACKGROUND: Through high-throughput next-generation sequencing of promoters of
solute carrier and ATP-binding cassette genes, which encode drug transporters, we
aimed to identify SNPs associated with the response to imatinib administered for
first-line treatment of patients with chronic myeloid leukemia. METHODS: In
silico analysis using publicly available databases was done to select the SLC and
ABC genes and their promoters for the next-generation sequencing. SNPs associated
with the imatinib response were identified using Fisher's exact probability tests
and subjected to the linkage disequilibrium analyses with regulatory loci of
concerned genes. We analyzed cumulative achievement of major molecular response
and probability of event free survival in relation to identified SNP genotypes in
129 CML patients and performed multivariate analysis for determination of
genotypes as independent predictors of outcome. Gene expression analysis of eight
cell lines naturally carrying different genotypes was performed to outline an
impact of genotypes on the gene expression. RESULTS: We observed significant
differences in the frequencies of the rs460089-GC and rs460089-GG (SLC22A4)
genotypes among rs2631365-TC (SLC22A5) genotype carriers that were associated
with optimal and non-optimal responses, respectively. Loci rs460089 and rs2631365
were in highly significant linkage disequilibrium with 12 regulatory loci in
introns of SLC22A4 and SLC22A5 encoding imatinib transporters. Genotype
association analysis with the response to imatinib indicated that rs460089-GC
carriers had a significantly higher probability of achieving a stable major
molecular response (BCR-ABL1 transcript level below or equal to 0.1% in the
international scale). In contrast, the rs460089-GG represented a risk factor for
imatinib failure, which was significantly higher in rs460089-GG_rs2631365-TC
carriers. CONCLUSIONS: This exploratory study depicted potentially important
genetic markers predicting outcome of imatinib treatment, which may be helpful
for tailoring therapy in clinical practice.
PMID- 28420427
TI - Isolation and characterization of equine native MSC populations.
AB - BACKGROUND: In contrast to humans in which mesenchymal stem/stromal cell (MSC)
therapies are still largely in the clinical trial phase, MSCs have been used
therapeutically in horses for over 15 years, thus constituting a valuable
preclinical model for humans. In human tissues, MSCs have been shown to originate
from perivascular cells, namely pericytes and adventitial cells, which are
identified by the presence of the cell surface markers CD146 and CD34,
respectively. In contrast, the origin of MSCs in equine tissues has not been
established, preventing the isolation and culture of defined cell populations in
that species. Moreover, a comparison between perivascular CD146+ and CD34+ cell
populations has not been performed in any species. METHODS: Immunohistochemistry
was used to identify adventitial cells (CD34+) and pericytes (CD146+) and to
determine their localization in relation to MSCs in equine tissues. Isolation of
CD34+ (CD34+/CD146-/CD144-/CD45-) and CD146+ (CD146+/CD34-/CD144-/CD45-) cell
fractions from equine adipose tissue was achieved by fluorescence-activated cell
sorting. The isolated cell fractions were cultured and analyzed for the
expression of MSC markers, using qPCR and flow cytometry, and for the ability to
undergo trilineage differentiation. Angiogenic properties were analyzed in vivo
using a chorioallantoic membrane (CAM) assay. RESULTS: Both CD34+ and CD146+
cells displayed typical MSC features, namely growth in uncoated tissue culture
dishes, clonal growth when seeded at low density, expression of typical MSC
markers, and multipotency shown by the capacity for trilineage differentiation.
Of note, CD146+ cells were distinctly angiogenic compared with CD34+ and non
sorted cells (conventional MSCs), demonstrated by the induction of blood vessels
in a CAM assay, expression of elevated levels of VEGFA and ANGPT1, and
association with vascular networks in cocultures with endothelial cells,
indicating that CD146+ cells maintain a pericyte phenotype in culture.
CONCLUSION: This study reports for the first time the successful isolation and
culture of CD146+ and CD34+ cell populations from equine tissues.
Characterization of these cells evidenced their distinct properties and MSC-like
phenotype, and identified CD146+ cells as distinctly angiogenic, which may
provide a novel source for enhanced regenerative therapies.
PMID- 28420428
TI - Significant heterogeneity in Wolbachia copy number within and between populations
of Onchocerca volvulus.
AB - BACKGROUND: Wolbachia are intracellular bacteria found in arthropods and several
filarial nematode species. The filarial Wolbachia have been proposed to be
involved in the immunopathology associated with onchocerciasis. Higher Wolbachia
to-nematode ratios have been reported in the savannah-ecotype compared to the
forest-ecotype, and have been interpreted as consistent with a correlation
between Wolbachia density and disease severity. However, factors such as
geographic stratification and ivermectin drug exposure can lead to significant
genetic heterogeneity in the nematode host populations, so we investigated
whether Wolbachia copy number variation is also associated with these underlying
factors. METHODS: Genomic DNA was prepared from single adult nematodes
representing forest and savannah ecotypes sampled from Togo, Ghana, Cote d'Ivoire
and Mali. A qPCR assay was developed to measure the number of Wolbachia genome(s)
per nematode genome. Next-generation sequencing (NGS) was also used to measure
relative Wolbachia copy number, and independently verify the qPCR assay. RESULTS:
Significant variation was observed within the forest (range: 0.02 to 452.99;
median: 10.58) and savannah (range: 0.01 to 1106.25; median: 9.10) ecotypes,
however, no significant difference between ecotypes (P = 0.645) was observed;
rather, strongly significant Wolbachia variation was observed within and between
the nine study communities analysed (P = 0.021), independent of ecotype. Analysis
of ivermectin-treated and untreated nematodes by qPCR showed no correlation (P =
0.869); however, an additional analysis of a subset of the nematodes by qPCR and
NGS revealed a correlation between response to ivermectin treatment and Wolbachia
copy number (P = 0.020). CONCLUSIONS: This study demonstrates that extensive
within and between population variation exists in the Wolbachia content of
individual adult O. volvulus. The origin and functional significance of such
variation (up to ~ 100,000-fold between worms; ~10 to 100-fold between
communities) in the context of the proposed mutualistic relationship between the
worms and the bacteria, and between the presence of Wolbachia and clinical
outcome of infection, remains unclear. These data do not support a correlation
between Wolbachia copy number and forest or savannah ecotype, and may have
implications for the development of anti-Wolbachia drugs as a macrofilaricidal
treatment of onchocerciasis. The biological significance of a correlation between
variation in Wolbachia copy number and ivermectin response remains unexplained.
PMID- 28420429
TI - DEPTOR maintains plasma cell differentiation and favorably affects prognosis in
multiple myeloma.
AB - BACKGROUND: The B cell maturation process involves multiple steps, which are
controlled by relevant pathways and transcription factors. The understanding of
the final stages of plasma cell (PC) differentiation could provide new insights
for therapeutic strategies in multiple myeloma (MM). Here, we explore the role of
DEPTOR, an mTOR inhibitor, in the terminal differentiation of myeloma cells, and
its potential impact on patient survival. METHODS: The expression level of DEPTOR
in MM cell lines and B cell populations was measured by real-time RT-PCR, and/or
Western blot analysis. DEPTOR protein level in MM patients was quantified by
capillary electrophoresis immunoassay. RNA interference was used to downregulate
DEPTOR in MM cell lines. RESULTS: DEPTOR knockdown in H929 and MM1S cell lines
induced dedifferentiation of myeloma cells, as demonstrated by the upregulation
of PAX5 and BCL6, the downregulation of IRF4, and a clear reduction in cell size
and endoplasmic reticulum mass. This effect seemed to be independent of mTOR
signaling, since mTOR substrates were not affected by DEPTOR knockdown.
Additionally, the potential for DEPTOR to be deregulated in MM by particular
miRNAs was investigated. The ectopic expression of miR-135b and miR-642a in
myeloma cell lines substantially diminished DEPTOR protein levels, and caused
dedifferentiation of myeloma cells. Interestingly, the level of expression of
DEPTOR protein in myeloma patients was highly variable, the highest levels being
associated with longer progression-free survival. CONCLUSIONS: Our results
demonstrate for the first time that DEPTOR expression is required to maintain
myeloma cell differentiation and that high level of its expression are associated
with better outcome. Primary samples used in this study correspond to patients
entered into GEM2010 trial (registered at www.clinicaltrials.gov as #NCT01237249,
4 November 2010).
PMID- 28420430
TI - Chronic stress induces CD99, suppresses autophagy, and affects spontaneous
adipogenesis in human bone marrow stromal cells.
AB - BACKGROUND: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent
cells with a high constitutive level of autophagy and low expression of CD99.
Under certain conditions, MSCs may develop tumorigenic properties. However, these
transformation-induced conditions are largely unknown. Recently, we have
identified an association between Hsp70, a main participant in cellular stress
response and tumorigenesis, and CD99. Preliminary observations had revealed
upregulation of both proteins in stressed long-term cultured MSCs. And so we
hypothesized that CD99 is implicated in stress-induced mechanisms of cellular
transformation in MSCs. Hence, we investigated the effects of prolonged stress on
MSCs and the role of CD99 and autophagy in their survival. METHODS: Human
telomerase reverse transcriptase (hTERT) overexpressing immortalized MSCs and
primary bone marrow stromal cells were used to investigate the influence of long
term serum deprivation and hypoxia on growth and differentiation of MSCs. Cell
proliferation and apoptosis were evaluated using flow cytometry, differentiation
capabilities of MSCs were assessed by immunohistochemical staining followed by
microscopic examination. CD99, Hsp70 expression were analyzed using flow
cytometry, western blotting, and reverse transcriptase polymerase chain reaction.
Autophagy was explored with specific inhibitors using cell morphology examination
and western blotting. RESULTS: Chronic stress factors are able to change the
morphology of MSCs and to inhibit spontaneous differentiation into adipocyte
lineage. Furthermore, CD99 elevation and downregulation of p53 and p21
accompanied defective autophagy, which is usually associated with tumor
formation. We found that inhibition of autophagy by chloroquine promoted cell
detachment and modulated CD99 expression level whereas incorporation of CD99
recombinant protein into the cells suppressed autophagy. CONCLUSIONS: Obtained
results provide a model for chronic stress-induced transformation of MSCs via
CD99 and may therefore be highly relevant to mesenchymal tumorigenesis.
PMID- 28420431
TI - Injuries in extreme sports.
AB - Extreme sports (ES) are usually pursued in remote locations with little or no
access to medical care with the athlete competing against oneself or the forces
of nature. They involve high speed, height, real or perceived danger, a high
level of physical exertion, spectacular stunts, and heightened risk element or
death.Popularity for such sports has increased exponentially over the past two
decades with dedicated TV channels, Internet sites, high-rating competitions, and
high-profile sponsors drawing more participants.Recent data suggest that the risk
and severity of injury in some ES is unexpectedly high. Medical personnel
treating the ES athlete need to be aware there are numerous differences which
must be appreciated between the common traditional sports and this newly
developing area. These relate to the temperament of the athletes themselves, the
particular epidemiology of injury, the initial management following injury,
treatment decisions, and rehabilitation.The management of the injured extreme
sports athlete is a challenge to surgeons and sports physicians. Appropriate
safety gear is essential for protection from severe or fatal injuries as the
margins for error in these sports are small.The purpose of this review is to
provide an epidemiologic overview of common injuries affecting the extreme
athletes through a focus on a few of the most popular and exciting extreme
sports.
PMID- 28420432
TI - Elevated Gab2 induces tumor growth and angiogenesis in colorectal cancer through
upregulating VEGF levels.
AB - BACKGROUND: Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves
as a critical signaling amplifier downstream of tyrosine kinase receptors. Our
previous study has shown that Gab2 induces epithelial-to-mesenchymal transition
(EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of
Gab2 in CRC growth and angiogenesis remains unclear. METHODS: The expression of
vascular endothelial growth factor (VEGF) in different colorectal tissues was
detected by immunohistochemistry and qRT-PCR to evaluate its correlation with
Gab2. Lentiviral vectors bearing Gab2 gene and its small interfering RNAs were
constructed and transfected into CRC cell lines. The effects of Gab2 on the cell
proliferation in vitro and tumorigenesis in vivo, were examined via CCK-8 assay,
colony formation assay as well as tumorigenicity assay respectively. Moreover, to
assess its potential role in tumor growth and angiogenesis, the expression of
Ki67, CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) were
detected by immunohistochemistry in CRC cells tumors. Finally, we evaluated the
impact of Gab2 on the expression of c-Myc and VEGF, and the probable effect of
mechanistic targeted extracellular signal-regulated kinase (ERK) pathway in
suppressing tumor growth and angiogenesis. RESULTS: Up-regulation of Gab2
expression was found to be positively correlated with VEGF in CRC tissues.
Exogenous expression of Gab2 obviously promoted, whereas silencing of Gab2
inhibited, proliferation and clone formation of human CRC cells in vitro. Of
note, Gab2 enhanced tumorigenesis and tumor growth in mouse xenografts with high
Ki67 expression, and led to an increased vessel density with strong CD34 and
VEGFR2 activity. In addition, elevated Gab2 expression obviously up-regulated the
expression of VEGF, and stimulated the activation of its downstream genes, ERK1/2
and c-Myc in CRC cells. Instead, down-regulated Gab2 expression significantly
reduced the levels of VEGF, and inhibited the transduction of ERK/c-Myc pathway.
Finally, we revealed that mechanistic target of mitogen-activated protein kinase
(MEK) could attenuate Gab2-induced tumor growth and angiogenesis via altering
VEGF and c-Myc levels. CONCLUSIONS: The results from our study suggest that Gab2
promotes intestinal tumor growth and angiogenesis through upregulation of VEGF
expression mediated by the MEK/ERK/c-Myc pathway.
PMID- 28420433
TI - Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen
degradation via upregulation of MMP-9 in rat uterine scars.
AB - BACKGROUND: Severe injuries of the uterus may trigger uterine scar formation,
ultimately leading to infertility or obstetrical complications. To date, few
methods have adequately solved the problem of collagen deposition in uterine
scars. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown great
promise in clinical applications. The objective of this study was to investigate
the effect of a scaffold/UC-MSCs construct on collagen degradation and functional
regeneration in rat uterine scars following full-thickness excision of uterine
walls. METHODS: In order to establish a rat model of uterine scars, the uterine
wall of approximately 1.0 cm in length and 0.5 cm in width (one-third of the
uterine circumference) was excised from each uterine horn. A total of 128 scarred
uterine horns from 64 rats were randomly assigned to four groups, including a PBS
group (n = 32 uterine horns), scaffold group (n = 32 uterine horns), UC-MSCs
group (n = 32 uterine horns) and scaffold/UC-MSCs group (n = 32 uterine horns) to
investigate the effect of different treatments on the structure and function of
uterine scars. PBS, degradable collagen fibres, UC-MSCs or UC-MSCs mixed with
gelatinous degradable collagen fibres were injected into four pre-marked points
surrounding each uterine scar, respectively. At days 30 and 60 post
transplantation, a subset of rats (n = 8 uterine horns) from each group was
euthanized and serial sections of uterine tissues containing the operative region
were prepared. Haematoxylin-eosin staining, Masson's trichrome staining, and
immunohistochemical staining for MMP-2, MMP-9, alpha-SMA and vWF were performed.
Finally, another subset of rats (n = 16 uterine horns) from each group was mated
with male rats at day 60 post-transplantation and euthanized 18 days after the
presence of vaginal plugs to check numbers, sizes and weights of fetuses, as well
as sites of implantation. RESULTS: The scaffold/UC-MSCs group exhibited obvious
collagen degradation compared with the other three groups. At day 60 post
transplantation, the number of MMP-9-positive cells in the scaffold/UC-MSCs group
(25.96 +/- 3.63) was significantly higher than that in the PBS group (8.19 +/-
1.61, P < 0.01), the scaffold group (7.25 +/- 2.17, P < 0.01) and the UC-MSCs
group (8.31 +/- 2.77, P < 0.01). The pregnancy rate in the scaffold/UC-MSCs group
(10/16) was also significantly higher than that in the PBS group (2/16, P <
0.017), the scaffold group (1/16, P < 0.017) and the UC-MSCs group (3/16, P <
0.017). CONCLUSIONS: The scaffold/UC-MSCs system facilitated collagen degradation
in uterine scars via upregulation of MMP-9, which was secreted by transplanted UC
MSCs, and promoted regeneration of the endometrium, myometrium and blood vessels
in uterine scars. Furthermore, the scaffold/UC-MSCs-treated uterine scars showed
nearly complete restoration of receptive fertility.
PMID- 28420435
TI - Comparison of the mechanical properties of different skin sites for auricular and
nasal reconstruction.
AB - BACKGROUND: Autologous and synthetic nasal and auricular frameworks require skin
coverage. The surgeon's decides on the appropriate skin coverage for
reconstruction based on colour matching, subcutaneous tissue thickness, expertise
and experience. One of the major complications of placing subcutaneous implants
is the risk of extrusion (migration through the skin) and infection. However,
knowledge of lessening the differential between the soft tissue and the framework
can have important implications for extrusion. This study compared the mechanical
properties of the skin commonly used as skin sites for the coverage in auricular
and nasal reconstruction. METHODS: Using ten fresh human cadavers, the tensile
Young's Modulus of the skin from the forehead, forearm, temporoparietal, post
auricular and submandibular neck was assessed. The relaxation rate and absolute
relaxation level was also assessed after 90 min of relaxation. RESULTS: The
submandibular skin showed the greatest Young's elastic modulus in tension of all
regions (1.28 MPa +/-0.06) and forearm showed the lowest (1.03 MPa +/-0.06). The
forehead demonstrated greater relaxation rates among the different skin regions
(7.8 MPa-07 +/- 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa
07 +/- 0.1). The forearm (0.04 MPa +/-0.004) and submandibular neck skin (0.04
MPa +/-0.005) showed similar absolute levels of relaxation, which were
significantly greater than the other skin regions (p < 0.05). CONCLUSIONS: This
study provides an understanding into the biomechanical properties of the skin of
different sites allowing surgeons to consider this parameter when trying to
identify the optimal skin coverage in nasal and auricular reconstruction.
PMID- 28420434
TI - The neuroprotective effects of human bone marrow mesenchymal stem cells are dose
dependent in TNBS colitis.
AB - BACKGROUND: The incidence of inflammatory bowel diseases (IBD) is increasing
worldwide with patients experiencing severe impacts on their quality of life. It
is well accepted that intestinal inflammation associates with extensive damage to
the enteric nervous system (ENS), which intrinsically innervates the
gastrointestinal tract and regulates all gut functions. Hence, treatments
targeting the enteric neurons are plausible for alleviating IBD and associated
complications. Mesenchymal stem cells (MSCs) are gaining wide recognition as a
potential therapy for many diseases due to their immunomodulatory and
neuroprotective qualities. However, there is a large discrepancy regarding
appropriate cell doses used in both clinical trials and experimental models of
disease. We have previously demonstrated that human bone marrow MSCs exhibit
neuroprotective and anti-inflammatory effects in a guinea-pig model of 2,4,6
trinitrobenzene-sulfonate (TNBS)-induced colitis; but an investigation into
whether this response is dose-dependent has not been conducted. METHODS: Hartley
guinea-pigs were administered TNBS or sham treatment intra-rectally. Animals in
the MSC treatment groups received either 1 * 105, 1 * 106 or 3 * 106 MSCs by
enema 3 hours after induction of colitis. Colon tissues were collected 72 hours
after TNBS administration to assess the effects of MSC treatments on the level of
inflammation and damage to the ENS by immunohistochemical and histological
analyses. RESULTS: MSCs administered at a low dose, 1 * 105 cells, had little or
no effect on the level of immune cell infiltrate and damage to the colonic
innervation was similar to the TNBS group. Treatment with 1 * 106 MSCs decreased
the quantity of immune infiltrate and damage to nerve processes in the colonic
wall, prevented myenteric neuronal loss and changes in neuronal subpopulations.
Treatment with 3 * 106 MSCs had similar effects to 1 * 106 MSC treatments.
CONCLUSIONS: The neuroprotective effect of MSCs in TNBS colitis is dose
dependent. Increasing doses higher than 1 * 106 MSCs demonstrates no further
therapeutic benefit than 1 * 106 MSCs in preventing enteric neuropathy associated
with intestinal inflammation. Furthermore, we have established an optimal dose of
MSCs for future studies investigating intestinal inflammation, the enteric
neurons and stem cell therapy in this model.
PMID- 28420436
TI - Autophagy mediates the beneficial effect of hypoxic preconditioning on bone
marrow mesenchymal stem cells for the therapy of myocardial infarction.
AB - BACKGROUND: Stem cell therapy has emerged as a promising therapeutic strategy for
myocardial infarction (MI). However, the poor viability of transplanted stem
cells hampers their therapeutic efficacy. Hypoxic preconditioning (HPC) can
effectively promote the survival of stem cells. The aim of this study was to
investigate whether HPC improved the functional survival of bone marrow
mesenchymal stem cells (BM-MSCs) and increased their cardiac protective effect.
METHODS: BM-MSCs, isolated from Tg(Fluc-egfp) mice which constitutively express
both firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP),
were preconditioned with HPC (1% O2) for 12 h, 24 h, 36 h, and 48 h,
respectively, followed by 24 h of hypoxia and serum deprivation (H/SD) injury.
RESULTS: HPC dose-dependently increased the autophagy in BM-MSCs. However, the
protective effects of HPC for 24 h are most pronounced. Moreover, hypoxic
preconditioned BM-MSCs (HPCMSCs) and nonhypoxic preconditioned BM-MSCs (NPCMSCs)
were transplanted into infarcted hearts. Longitudinal in vivo bioluminescence
imaging (BLI) and immunofluorescent staining revealed that HPC enhanced the
survival of engrafted BM-MSCs. Furthermore, HPCMSCs significantly reduced
fibrosis, decreased apoptotic cardiomyocytes, and preserved heart function.
However, the beneficial effect of HPC was abolished by autophagy inhibition with
3-methyladenine (3-MA) and Atg7siRNA. CONCLUSION: This study demonstrates that
HPC may improve the functional survival and the therapeutic efficiencies of
engrafted BM-MSCs, at least in part through autophagy regulation. Hypoxic
preconditioning may serve as a promising strategy for optimizing cell-based
cardiac regenerative therapy.
PMID- 28420437
TI - Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration.
AB - An intronic GGGGCC expansion in C9orf72 is the most common known cause of both
frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS).
The repeat expansion leads to the generation of sense and antisense repeat RNA
aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated
non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR)
and poly(proline-arginine or PR) are potently neurotoxic and can localise to the
nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted
functionality. Furthermore, GGGGCC repeat RNA can bind nucleolar proteins in
vitro. However, the relevance of nucleolar stress is unclear, as the arginine
rich DPR proteins do not localise to the nucleolus in C9orf72-associated FTLD/ALS
(C9FTLD/ALS) patient brain. We measured nucleolar size in C9FTLD frontal cortex
neurons using a three-dimensional, volumetric approach. Intriguingly, we found
that C9FTLD brain exhibited bidirectional nucleolar stress. C9FTLD neuronal
nucleoli were significantly smaller than control neuronal nucleoli. However,
within C9FTLD brains, neurons containing poly(GR) inclusions had significantly
larger nucleolar volumes than neurons without poly(GR) inclusions. In addition,
expression of poly(GR) in adult Drosophila neurons led to significantly enlarged
nucleoli. A small but significant increase in nucleolar volume was also observed
in C9FTLD frontal cortex neurons containing GGGGCC repeat-containing RNA foci.
These data show that nucleolar abnormalities are a consistent feature of C9FTLD
brain, but that diverse pathomechanisms are at play, involving both DPR protein
and repeat RNA toxicity.
PMID- 28420438
TI - Distance traveled for Medicaid-covered abortion care in California.
AB - BACKGROUND: Access to abortion care in the United States is limited by the
availability of abortion providers and their geographic distribution. We aimed to
assess how far women travel for Medicaid-funded abortion in California and
identify disparities in access to abortion care. METHODS: We obtained data on all
abortions reimbursed by the fee-for-service California state Medicaid program
(Medi-Cal) in 2011 and 2012 and examined distance traveled to obtain abortion
care by several demographic and abortion-related factors. Mixed-effects
multivariable logistic regression models were constructed to examine factors
associated with traveling 50 miles or more. County-level t-tests and linear
regressions were conducted to examine the effects of a Medi-Cal abortion provider
in a county on overall and urban/rural differences in utilization. RESULTS: 11.9%
(95% CI: 11.5-12.2%) of women traveled 50 miles or more. Women obtaining second
trimester or later abortions (21.7%), women obtaining abortions at hospitals
(19.9%), and rural women (51.0%) were most likely to travel 50 miles or more.
Across the state, 28 counties, home to 10% of eligible women, did not have a
facility routinely providing Medi-Cal-covered abortions. CONCLUSIONS: Efforts are
needed to expand the number of abortion providers that accept Medi-Cal. This
could be accomplished by increasing Medi-Cal reimbursement rates, increasing the
types of providers who can provide abortions, and expanding the use of
telemedicine. If national trends in declining unintended pregnancy and abortion
rates continue, careful attention should be paid to ensure that reduced demand
does not lead to greater disparities in geographic and financial access to
abortion care by ensuring that providers accepting Medicaid payment are available
and widely distributed.
PMID- 28420439
TI - Fragile X syndrome: a review of clinical and molecular diagnoses.
AB - BACKGROUND: Fragile X Syndrome (FXS) is the second cause of intellectual
disability after Down syndrome and the most prevalent cause of intellectual
disability in males, affecting 1:5000-7000 men and 1:4000-6000 women. It is
caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more
than 99% of individuals have a CGG expansion (>200 triplets) in the 5' UTR of the
gene, and FMR1 mutations and duplication/deletion are responsible for the
remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather
the current clinical and molecular knowledge about FXS to provide clinicians with
a tool to guide the initial assessment and follow-up of FXS and to offer to
laboratory workers and researchers an update about the current diagnostic
procedures. DISCUSSION: FXS is a well-known condition; however, most of the
studies thus far have focused on neuropsychiatric features. Unfortunately, some
of the available studies have limitations, such as the paucity of patients
enrolled or bias due to the collection of the data in a single-country
population, which may be not representative of the average global FXS population.
In recent years, insight into the adult presentation of the disease has
progressively increased. Pharmacological treatment of FXS is essentially symptom
based, but the growing understanding of the molecular and biological mechanisms
of the disease are paving the way to targeted therapy, which may reverse the
effects of FMRP deficiency and be a real cure for the disease itself, not just
its symptoms. CONCLUSIONS: The clinical spectrum of FXS is wide, presenting not
only as an isolated intellectual disability but as a multi-systemic condition,
involving predominantly the central nervous system but potentially affecting any
apparatus. Given the relative high frequency of the condition and its complex
clinical management, FXS appears to have an important economic and social burden.
PMID- 28420440
TI - Immune response after autologous hematopoietic stem cell transplantation in type
1 diabetes mellitus.
AB - BACKGROUND: This study explored the details of the immune response after
autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1
diabetes mellitus. METHODS: Peripheral blood mononuclear cells (PBMCs) from 18
patients with type 1 diabetes mellitus were taken at baseline and 12 months after
AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and
secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T
helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in
PBMC culture supernatants were assessed. RESULTS: Compared with patients
receiving insulin-only treatment, the patients receiving AHSCT treatment showed
better residual C-peptide secretion, lower anti-GAD titers and less exogenous
insulin dosages after 12 months of follow-up. AHSCT treatment was associated with
significantly reduced Th1 and Th17 cell proportions as well as decreased IFN
gamma, IL-2, IL-12p40 and IL-17A levels in the PBMC culture supernatants (all P <
0.05). Although there was no significant Treg cell expansion after AHSCT
treatment, we observed increased IL-10, TGF-beta and Foxp3 mRNA expression and
increased TGF-beta levels. However, we found no significant changes in the T-cell
subpopulations after insulin treatment, except for higher IL-12p40 mRNA
expression and a lower proportion of Treg cells. CONCLUSIONS: AHSCT treatment was
associated with decreased expansion and function of Th1 and Th17 cells, which may
explain the better therapeutic effect of AHSCT compared with the traditional
intensive insulin therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00807651 .
Registered 18 December 2008.
PMID- 28420441
TI - Autologous bone marrow-derived cell transplantation in decompensated alcoholic
liver disease: what is the impact on liver histology and gene expression
patterns?
AB - BACKGROUND: Liver stem cell therapy (SCT) has been suggested as a promising means
to improve liver regeneration in advanced liver disease. However, data from
trials are heterogeneous, with no systematic histological evaluation. The aim of
this study is to specifically analyze the effect of autologous SCT on liver
regeneration and on gene expression changes. METHODS: Individuals in the
randomized controlled trial of SCT in alcoholic hepatitis with paired liver
biopsies were included (n = 58). Immunohistochemistry (Ki67, K7, and CD68), in
situ hybridization (SPINK1), and global gene expression analysis were performed
on liver biopsies (30 control patients and 28 patients with transarterial
administration of bone marrow-derived stem cells) both at baseline and after 4
weeks of follow-up. RESULTS: No difference between the two groups could be
observed regarding the proliferative hepatocyte number, proliferative K7-positive
cells, or total K7-positive cells at the 4-week follow-up liver biopsy. However,
patients who received SCT showed a more important liver macrophagic expansion as
compared to standard treatment. Transcriptome data revealed changes in genes
linked with inflammation (CD68 and SAA), regeneration (SPINK1 and HGF), fibrosis
(COL1A1), and stem cells (CD45). No changes in gene pathways involved in liver
growth and cell cycle proteins were evident. SPINK1 mRNA was present by in situ
hybridization at week 4 in SCT patients in the liver parenchyma areas adjacent to
macrophage recruitment and liver cell proliferation. CONCLUSIONS: The analysis of
liver tissue after SCT demonstrated an expansion of macrophages concurrent with
an upregulated expression of genes involved in inflammatory and regenerative
pathways. With the negative results from the clinical trial, the impact of the
SCT has to be interpreted as weak, and it is not able to modify the clinical
course of this severe liver disease.
PMID- 28420442
TI - Updated systematic review: associations between proximity to animal feeding
operations and health of individuals in nearby communities.
AB - OBJECTIVE: The objective of this review was to update a systematic review of
associations between living near an animal feeding operation (AFO) and human
health. METHODS: The MEDLINE(r) and MEDLINE(r) In-Process, Centre for
Agricultural Biosciences Abstracts, and Science Citation Index databases were
searched. Reference lists of included articles were hand-searched. Eligible
studies reported exposure to an AFO and an individual-level human health outcome.
Two reviewers performed study selection and data extraction. RESULTS: The search
returned 3702 citations. Sixteen articles consisting of 10 study populations were
included in the analysis. The health outcomes were lower and upper respiratory
tracts, MRSA, other infectious disease, neurological, psychological,
dermatological, otologic, ocular, gastrointestinal, stress and mood, and other
non-infectious health outcomes. Most studies were observational and used
prevalence measures of outcome. An association between Q fever risk and proximity
to goat production was reported. Other associations were unclear. Risk of bias
was serious or critical for most exposure-outcome associations. Multiplicity
(i.e., a large number of potentially correlated outcomes and exposures assessed
on the same study subjects) was common in the evidence base. CONCLUSIONS: Few
studies reported an association between surrogate clinical outcomes and AFO
proximity for respiratory tract-related outcomes. There were no consistent dose
response relationships between surrogate clinical outcome and AFO proximity. A
new finding was that Q fever in goats is likely associated with an increased Q
fever risk in community members. The review results for the non-respiratory
health outcomes were inconclusive because only a small number of studies were
available or the between-study results were inconsistent. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42014010521.
PMID- 28420443
TI - Tau phosphorylation induced by severe closed head traumatic brain injury is
linked to the cellular prion protein.
AB - Studies in vivo and in vitro have suggested that the mechanism underlying
Alzheimer's disease (AD) neuropathogenesis is initiated by an interaction between
the cellular prion protein (PrPC) and amyloid-beta oligomers (Abetao). This PrPC
Abetao complex activates Fyn kinase which, in turn, hyperphosphorylates tau (P
Tau) resulting in synaptic dysfunction, neuronal loss and cognitive deficits. AD
transgenic mice lacking PrPC accumulate Abeta, but show normal survival and no
loss of spatial learning and memory suggesting that PrPC functions downstream of
Abetao production but upstream of intracellular toxicity within neurons. Since AD
and traumatic brain injury (TBI)-linked chronic traumatic encephalopathy are
tauopathies, we examined whether similar mechanistic pathways are responsible for
both AD and TBI pathophysiologies. Using transgenic mice expressing different
levels of PrPC, our studies investigated the influence and necessity of PrPC on
biomarker (total-tau [T-Tau], P-Tau, GFAP) levels in brain and blood as measured
biochemically following severe TBI in the form of severe closed head injury
(sCHI). We found that following sCHI, increasing levels of T-Tau and P-Tau in the
brain were associated with the PrPC expression levels. A similar relationship
between PrPC expression and P-Tau levels following sCHI were found in blood in
the absence of significant T-Tau changes. This effect was not seen with GFAP
which increased within 24 h following sCHI and progressively decreased by the 7
day time point regardless of the PrPC expression levels. Changes in the levels of
all biomarkers were independent of gender. We further enhanced and expanded the
quantitation of brain biomarkers with correlative studies using
immunohisochemistry. We also demonstrate that a TBI-induced calpain
hyperactivation is not required for the generation of P-Tau. A relationship was
demonstrated between the presence/absence of PrPC, the levels of P-Tau and
cognitive dysfunction. Our studies suggest that PrPC is important in mediating
TBI related pathology.
PMID- 28420444
TI - Case report: ACTH-secreting pituitary carcinoma metastatic to the liver in a
patient with a history of atypical pituitary adenoma and Cushing's disease.
AB - BACKGROUND: Pituitary carcinoma is a rare entity requiring the presence of
metastasis to confirm its malignant potential. We report a case of pituitary
carcinoma and discuss the diagnosis and management of this lesion in relation to
the existing literature. CASE PRESENTATION: The patient is a 51-year-old woman
with Cushing's disease and intact adrenal glands who was diagnosed with
metastatic pituitary carcinoma to the liver, 29 months after initial resection of
an ACTH-secreting primary atypical pituitary adenoma (APA). Prior to detection of
this metastasis the patient underwent repeat resection and radiotherapy for
residual cavernous sinus disease. The metastatic lesion was detected by interval
surveillance of serum ACTH and 24-hour urine cortisol, which despite stable
pituitary MRI, were significantly elevated. These abnormalities prompted a PET
scan that demonstrated hypermetabolic liver parenchyma, which was suspicious for
metastasis on abdominal MRI. An ultrasound-guided liver biopsy demonstrated nests
of moderately-differentiated cells with intermediate-sized, monotonous nuclei,
distinct nucleoli, and abundant basophilic cytoplasm, confirmed by
immunohistochemistry to represent metastatic pituitary carcinoma. The liver
lesion was subsequently successfully removed by wedge resection. One year later,
the patient's residual cavernous sinus disease grew markedly, and she was placed
on dual-agent chemotherapy consisting of oral temozolomide and capecitabine, with
stabilization of her intracranial disease to present, although liver metastases
recurred. CONCLUSIONS: Pituitary carcinoma is a rare entity impossible to
recognize as a primary tumor because its diagnosis by definition requires the
presence of metastasis. Maintaining awareness of the entity and its precursor
lesion APA is essential for its accurate pathologic diagnosis and appropriate
management.
PMID- 28420445
TI - Investigation of the association between the TCF7L2 rs7903146 (C/T) gene
polymorphism and obesity in a Cameroonian population: a pilot study.
AB - OBJECTIVE: This study aimed at investigating the association between the
rs7903146 (C/T) polymorphism of the TCF7L2 gene with obesity in a Cameroonian
population. METHOD: This was a case-control pilot study including 61 obese and 61
non-obese Cameroonian adults. Anthropometric indices of obesity, blood pressure,
fasting blood glucose, and blood lipids were measured. The rs7903146 (C/T)
polymorphism of the TCF7L2 gene was genotyped using polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP), and genotypes were
correlated with clinical and biological parameters. RESULTS: The T allele was
predominant in the study population with a frequency of 93%. No statistically
significant difference was however observed between the genotypic (p = 0.50) and
allelic frequencies (p = 0.58) of obese and non-obese subjects. Comparison of
clinical and biochemical parameters of C allele carriers (CX = CC + CT) with
those of TT genotype showed that there was no significant difference between the
lipid profile of these two groups. CONCLUSION: The rs7903146 (C/T) polymorphism
of the TCF7L2 gene might not be associated with obesity in the Cameroonian
population.
PMID- 28420446
TI - Immune resistance and tolerance strategies in malaria vector and non-vector
mosquitoes.
AB - BACKGROUND: The Anopheles gambiae complex consists of species that vary greatly
in their capacity to transmit malaria. The mosquito immune system has been
identified as a key factor that can influence whether Plasmodium infection
establishes within the mosquito vector. This study was designed to investigate
the immune responses of An. coluzzii, An. arabiensis and An. quadriannulatus
mosquitoes. The first two mosquito species are major vectors of malaria in sub
Saharan Africa, while the third is thought to be a non-vector. METHODS: All three
mosquito species were reared in mixed cultures. Their capacity to eliminate P.
berghei and regulate midgut bacteria was examined. RESULTS: Our results revealed
large differences in mosquito resistance to P. berghei. In all three mosquito
species, immune reactions involving the complement system were triggered when the
number of parasites that mosquitoes were challenged with exceeded a certain
level, i.e. immune tolerance threshold. This threshold was markedly lower in An.
quadriannulatus compared to An. coluzzii and An. arabiensis. We also demonstrated
that the level of immune tolerance to P. berghei infection in the haemolymph is
inversely correlated with the level of immune tolerance to microbiota observed in
the midgut lumen after a blood meal. The malaria non-vector mosquito species, An.
quadriannulatus was shown to have a much higher level of tolerance to microbiota
in the midgut than An. coluzzii. CONCLUSIONS: We propose a model whereby an
increased tolerance to microbiota in the mosquito midgut results in lower
tolerance to Plasmodium infection. In this model, malaria non-vector mosquito
species are expected to have increased immune resistance in the haemocoel,
possibly due to complement priming by microbiota elicitors. We propose that this
strategy is employed by the malaria non-vector mosquito, An. quadriannulatus,
while An. coluzzii has reduced tolerance to bacterial infection in the midgut and
consequently reduced immune resistance to Plasmodium infection at the haemocoel
level. An in-depth understanding of the molecular mechanisms regulating immune
tolerance versus resistance in different mosquito vectors of malaria could guide
the design of new vector and disease control strategies.
PMID- 28420449
TI - Interpersonal harm aversion as a necessary foundation for morality: A
developmental neuroscience perspective.
AB - Growing evidence from developmental psychology and social neuroscience emphasizes
the importance of third-party harm aversion for constructing morality. A
sensitivity to interpersonal harm emerges very early in ontogeny, as reflected in
both the capacity for implicit social evaluation and an aversion for antisocial
agents. Yet it does not necessarily entail avoidance toward inflicting pain to
others. Later, an understanding that harmful actions cause suffering emerges,
followed by an integration of rules that can depend on social contexts and
cultures. These developmental findings build on a burgeoning literature, which
suggests that the fundamental nature of moral and social cognition, including
their motivational and hedonic value, lies in general computational processes
such as attention, approach-avoidance, social valuation, and decision making
rather than in fully distinct, dedicated neural regions for morality. Bridging
the gap between cognition and behaviors and the requisite affective,
motivational, and cognitive mechanisms, a developmental neuroscience approach
enriches our understanding of the emergence of morality.
PMID- 28420447
TI - CK2.1, a bone morphogenetic protein receptor type Ia mimetic peptide, repairs
cartilage in mice with destabilized medial meniscus.
AB - BACKGROUND: Osteoarthritis (OA) of the knee involves degeneration of articular
cartilage of the diarthrodial joints. Current treatment options temporarily
relieve the joint pain but do not restore the lost cartilage. We recently
designed a novel bone morphogenetic protein receptor type I (BMPRI) mimetic
peptide, CK2.1, that activates BMPRIa signaling in the absence of bone
morphogenetic protein (BMP). Our previous research demonstrated that CK2.1
induced chondrogenesis in vitro and in vivo; however, it is unknown if CK2.1
restores damaged articular cartilage in vivo. In this study, we demonstrate that
CK2.1 induced articular cartilage (AC) repair in an OA mouse model. METHODS: We
designed hyaluronic acid (HA)-based hydrogel particles (HGPs) that slowly release
CK2.1. HGP-CK2.1 particles were tested for chondrogenic potency on pluripotent
mesenchymal stem cells (C3H10T1/2 cells) and locally injected into the intra
articular capsule in mice with cartilage defects. C57BL/6J mice were operated on
to destabilize the medial meniscus and these mice were kept for 6 weeks after
surgery to sustain OA-like damage. Mice were then injected via the intra
articular capsule with HGP-CK2.1; 4 weeks after injection the mice were
sacrificed and their femurs were analyzed for cartilage defects. RESULTS:
Immunohistochemical analysis of the cartilage demonstrated complete repair of the
AC compared to sham-operated mice. Immunofluorescence analysis revealed collagen
type IX production along with collagen type II in the AC of mice injected with
HGP-CK2.1. Mice injected with phosphate-buffered saline (PBS) and HGP alone had
greater collagen type X and osteocalcin production, in sharp contrast to those
injected with HGP-CK2.1, indicating increased chondrocyte hypertrophy.
CONCLUSIONS: Our results demonstrate that the slow release HGP-CK2.1 drives
cartilage repair without the induction of chondrocyte hypertrophy. The peptide
CK2.1 could be a powerful tool in understanding the signaling pathways
contributing to the repair process, and also may be used as a potential
therapeutic for treating degenerative cartilage diseases such as OA.
PMID- 28420448
TI - Association of cognitive function and liability to addiction with childhood
herpesvirus infections: A prospective cohort study.
AB - Liability to substance use disorder (SUD) is largely nonspecific to particular
drugs and is related to behavior dysregulation, including reduced cognitive
control. Recent data suggest that cognitive mechanisms may be influenced by
exposure to neurotropic infections, such as human herpesviruses. In this study,
serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1
(HSV-1), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) as well as
Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174
daughters of fathers with or without SUD. Its relationships with a cognitive
characteristic (IQ) in childhood and with risk for SUD in adulthood were examined
using correlation, regression, survival, and path analyses. Exposure to HSV-1,
EBV, and T. gondii in males and females, and CMV in males, was associated with
lower IQ. Independent of that relationship, EBV in females and possibly in males,
and CMV and possibly HSV-1 in females were associated with elevated risk for SUD.
Therefore, childhood neurotropic infections may influence cognitive development
and risk for behavior disorders such as SUD. The results may point to new avenues
for alleviating cognitive impairment and SUD risk.
PMID- 28420451
TI - What leads to high antipsychotic dosing in forensic patients with schizophrenia?
AB - Earlier findings suggest that forensic schizophrenia patients are treated with
higher doses of antipsychotics. This practice-based specificity is insufficiently
studied, and clinicians' motives regarding this practice remain poorly
understood. In this editorial, the authors provide their data on treatment of
forensic schizophrenia patients and identify characteristics of psychopathology
and previous types of behaviors, including suicidal attempts, as potential
reasons for the practice. They also emphasize that "these previous acts" often
took place years ago, and suggest that current or recent aggression is unlikely
the main reason for dosing, but rather the clinicians' intention to maintain
"must remain unaggressive" condition. Therefore, the authors suggest new ideas
that may contribute to a better understanding of the specific prescribing
patterns in the forensic population and hope that these ideas would be
implemented in further well-designed prospective studies.
PMID- 28420450
TI - What side effects are problematic for patients prescribed antipsychotic
medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.
AB - BACKGROUND: Capturing service users' perspectives can highlight additional and
different concerns to those of clinicians, but there are no up to date, self
report psychometrically sound measures of side effects of antipsychotic
medications. Aim To develop a psychometrically sound measure to identify
antipsychotic side effects important to service users, the Maudsley Side Effects
(MSE) measure. METHOD: An initial item bank was subjected to a Delphi exercise (n
= 9) with psychiatrists and pharmacists, followed by service user focus groups
and expert panels (n = 15) to determine item relevance and language. Feasibility
and comprehensive psychometric properties were established in two samples (N43
and N50). We investigated whether we could predict the three most important side
effects for individuals from their frequency, severity and life impact. RESULTS:
MSE is a 53-item measure with good reliability and validity. Poorer mental and
physical health, but not psychotic symptoms, was related to side-effect burden.
Seventy-nine percent of items were chosen as one of the three most important
effects. Severity, impact and distress only predicted 'putting on weight' which
was more distressing, more severe and had more life impact in those for whom it
was most important. CONCLUSIONS: MSE is a self-report questionnaire that
identifies reliably the side-effect burden as experienced by patients.
Identifying key side effects important to patients can act as a starting point
for joint decision making on the type and the dose of medication.
PMID- 28420452
TI - Fathering moderates the effects of maternal depression on the family process.
AB - Maternal depression negatively impacts children's development, yet few studies
have focused on fathering and the family process in cases of maternal depression.
A community cohort of married/cohabitating women was recruited on the second
postbirth day (N = 1,983) and maternal depression repeatedly assessed across the
first year and again at 6 years to form two cohorts: mothers chronically
depressed from birth to 6 (N = 46) and nondepressed controls (N = 103). At 6
years, mother-child, father-child, and family interactions were observed. In
families of depressed mothers, both mother and father exhibited lower sensitivity
and higher intrusiveness, and children displayed lower social engagement during
interactions with mother and father. Fathering moderated the effects of maternal
depression on the family process. When fathers showed low sensitivity, high
intrusiveness, and provided little opportunities for child social engagement, the
family process was less cohesive, implying a decrease in the family's harmonious,
warm, and collaborative style. However, in cases of high father sensitivity, low
intrusiveness, and increased child engagement, the family process was unaffected
by maternal depression. Findings describe both comparability and compensatory
mechanisms in the effects of fathering on family life when maternal care is
deficient, highlight the buffering role of fathers, and underscore the importance
of father-focused interventions when mothers are depressed.
PMID- 28420453
TI - Golden Years or Retirement Fears? Private Pension Inequality Among Canada's
Immigrants.
AB - Currently, many immigrants are disqualified from Canada's public pension scheme
because of residency requirements. In addition, decades of low income and labour
market exclusion prohibit many Canadian immigrants from building adequate private
pension savings throughout their working life. Together, these factors present
serious concerns for immigrant seniors' economic well-being. Using Canadian
census data spanning a twenty-year period (1991-2011), we find that income from
personal savings plans and investments has declined sharply for both native-born
and immigrant Canadians, with recent immigrant cohorts faring worst. However,
since 1991, native-born and immigrant men living in Canada for 40-plus years had
major gains in private employer pensions (Registered Pension Plans; [RPPs]). Yet
RPP income for all other immigrant cohorts remained stable or declined during
these decades. Thus, the data demonstrate a worrisome growing private savings gap
between native-born men and all others in Canada, with newer immigrants and women
faring worst.
PMID- 28420455
TI - Nutrient profiling for product reformulation: public health impact and benefits
for the consumer.
AB - The food industry holds great potential for driving consumers to adopt healthy
food choices as (re)formulation of foods can improve the nutritional quality of
these foods. Reformulation has been identified as a cost-effective intervention
in addressing non-communicable diseases as it does not require significant
alterations of consumer behaviour and dietary habits. Nutrient profiling (NP),
the science of categorizing foods based on their nutrient composition, has
emerged as an essential tool and is implemented through many different profiling
systems to guide reformulation and other nutrition policies. NP systems should be
adapted to their specific purposes as it is not possible to design one system
that can equally address all policies and purposes, e.g. reformulation and
labelling. The present paper discusses some of the key principles and
specificities that underlie a NP system designed for reformulation with the
example of the Nestle nutritional profiling system. Furthermore, the impact of
reformulation at the level of the food product, dietary intakes and public health
are reviewed. Several studies showed that food and beverage reformulation, guided
by a NP system, may be effective in improving population nutritional intakes and
thereby its health status. In order to achieve its maximum potential and modify
the food environment in a beneficial manner, reformulation should be implemented
by the entire food sector. Multi-stakeholder partnerships including governments,
food industry, retailers and consumer associations that will state concrete time
bound objectives accompanied by an independent monitoring system are the
potential solution.
PMID- 28420456
TI - Impaired Comprehension of Speed Verbs in Parkinson's Disease.
AB - OBJECTIVES: A wealth of studies provide evidence for action simulation during
language comprehension. Recent research suggests such action simulations might be
sensitive to fine-grained information, such as speed. Here, we present a crucial
test for action simulation of speed in language by assessing speed comprehension
in patients with Parkinson's disease (PD). Based on the patients' motor deficits,
we hypothesized that the speed of motion described in language would modulate
their performance in semantic tasks. Specifically, they would have more
difficulty processing language about relatively fast speed than language about
slow speed. METHODS: We conducted a semantic similarity judgment task on fast and
slow action verbs in patients with PD and age-matched healthy controls.
Participants had to decide which of two verbs most closely matched a target word.
RESULTS: Compared to controls, PD patients were slower making judgments about
fast action verbs, but not for judgments about slow action verbs, suggesting
impairment in processing language about fast action. Moreover, this impairment
was specific to verbs describing fast action performed with the hand.
CONCLUSIONS: Problems moving quickly lead to difficulties comprehending language
about moving quickly. This study provides evidence that speed is an important
part of action representations. (JINS, 2017, 23, 412-420).
PMID- 28420454
TI - Genetic and environmental influences on the codevelopment among borderline
personality disorder traits, major depression symptoms, and substance use
disorder symptoms from adolescence to young adulthood.
AB - Although borderline personality disorder (BPD) traits decline from adolescence to
adulthood, comorbid psychopathology such as symptoms of major depressive disorder
(MDD), alcohol use disorder (AUD), and drug use disorders (DUDs) likely disrupt
this normative decline. Using a longitudinal sample of female twins (N = 1,763),
we examined if levels of BPD traits were correlated with changes in MDD, AUD, and
DUD symptoms from ages 14 to 24. A parallel process biometric latent growth model
examined the contributions of genetic and environmental factors to the
relationships between developmental components of these phenotypes. Higher BPD
trait levels predicted a greater rate of increase in AUD and DUD symptoms, and
higher AUD and DUD symptoms predicted a slower rate of decline of BPD traits from
ages 14 to 24. Common genetic influences accounted for the associations between
BPD traits and each disorder, as well as the interrelationships of AUD and DUD
symptoms. Both genetic and nonshared environmental influences accounted for the
correlated levels between BPD traits and MDD symptoms, but solely environmental
influences accounted for the correlated changes between the two over time.
Results indicate that higher levels of BPD traits may contribute to an earlier
onset and faster escalation of AUD and DUD symptoms, and substance use problems
slow the normative decline in BPD traits. Overall, our data suggests that
primarily genetic influences contribute to the comorbidity between BPD features
and substance use disorder symptoms. We discuss our data in the context of two
major theories of developmental psychopathology and comorbidity.
PMID- 28420457
TI - Are impairments in emotion recognition a core feature of callous-unemotional
traits? Testing the primary versus secondary variants model in children.
AB - The role of environmental adversity in the development of high callous
unemotional (CU) traits in children is controversial. Evidence speaks to the
traits being largely independent of adversity; however, recent data shows that
those with high CU traits and high adversity and/or high anxiety might differ in
important ways from those with no such history. We tested this using emotion
recognition (ER) skills. We tested whether maltreatment history and anxiety
levels moderated the relationship between level of CU traits and ER skills in N =
364 children with behavioral problems who were 3 to 16 years old. As
hypothesised, in the full sample, the relationship between CU traits and ER
differed according to maltreatment history, such that CU traits were associated
with poorer recognition for those with zero or negligible history of
maltreatment. This moderation of the CU-ER relationship by maltreatment was
inconsistent across subgroups, however, and for the cohort utilizing youth self
report of maltreatment, high CU traits were associated with poor ER in those with
lower anxiety levels. Maltreatment history and/or anxiety levels can identify
different emotional impairments associated with high CU traits, and the
impairments might be characteristic of "primary" high CU traits defined as
occurring independently of maltreatment and/or high anxiety.
PMID- 28420459
TI - [Comparison between the international and the Japanese guidelines for the
management of sepsis and septic shock 2016].
PMID- 28420458
TI - Potentially important periods of change in the development of social and role
functioning in youth at clinical high risk for psychosis.
AB - The developmental course of daily functioning prior to first psychosis-onset
remains poorly understood. This study explored age-related periods of change in
social and role functioning. The longitudinal study included youth (aged 12-23,
mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis
(converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy
control group (n = 164). Mixed-model analyses were performed to determine age
related differences in social and role functioning. We limited our analyses to
functioning before psychosis conversion; thus, data of CHR-C participants
gathered after psychosis onset were excluded. In controls, social and role
functioning improved over time. From at least age 12, functioning in CHR was
poorer than in controls, and this lag persisted over time. Between ages 15 and
18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who
continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement
between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A
similar period of stagnation was apparent for role functioning, but to a lesser
extent (p = .007). The results remained consistent when we accounted for the time
to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in
social and role functioning in adolescence, followed by a period of further
stagnation in adulthood.
PMID- 28420460
TI - [Bone marrow mesenchymal stem cells modulated the inflammatory response by
regulating the expression of IL-4 and RAGE products in the rats with MODS].
AB - OBJECTIVE: To investigate the underlying mechanism of bone marrow mesenchymal
stem cells (BMSC) modulating the inflammatory response during the multiple organ
dysfunction syndrome (MODS), especially the expression of inflammatory cytokines,
which will provide new theoretical and experimental basis of MODS in clinic.
METHODS: BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and
cultivated, and the 4th passage were used in experimental study. According to the
random number table, 60 female SD rats were divided into three groups (n = 20 per
group): sham group, MODS group, BMSC group. MODS model in rats was induced by
lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was
injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC
group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation
(1*106/cells) through the tail vein. The survival rate was observed after 72
hours in each group. Abdominal aortic blood was collected for routine blood and
biochemical examination at 72 hours after operation. Protein microarray was used
to detect the related 34 inflammatory cytokines. Signal ratio was defined as the
differentially expressed factors when it was more than 2.0 or less than 0.5. And
enzyme linked immunosorbent assay (ELISA) was be applied to validate the
significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue
was harvested, then their pathological changes were observed by hematoxylin eosin
(HE) staining. RESULTS: 20, 12, 16 rats lived in sham group, MODS group and BMSC
group respectively at 72 hours after operation. Compared with the sham group, the
indicators (routine blood, liver and kidney function, myocardial enzyme) were
apparently unusual, and the heart, kidney, intestine tissue were injured
obviously in the MODS group. After BMSC administration, the organ function was
improved and tissue damaged was alleviated significantly. Protein microarray
showed that interleukin-4 (IL-4) and receptor for advanced glycation end products
(RAGE) were significantly different in 34 goal cytokines. The signal ratio change
of IL-4 was 0.397, 1.124, 2.826 respectively, and the signal ratio of RAGE was
6.197, 1.552, 0.250, respectively in MODS/sham group, BMSC/sham group, BMSC/MODS
group. ELISA validated the result that the expression level of IL-4 decreased
significantly (ng/L: 3.59+/-1.21 vs. 29.10+/-5.78) and the expression level of
RAGE increased significantly (ng/L: 1.09+/-0.04 vs. 0.11+/-0.03) in MODS group as
compared with sham group (both P < 0.05). Compared with the MODS group, the level
of IL-4 was obviously higher than that in BMSC group (ng/L: 9.59+/-2.21 vs.
3.59+/-1.21, P < 0.01), and RAGE decreased significantly (ng/L: 0.29+/-0.07 vs.
1.09+/-0.04, P < 0.05). CONCLUSIONS: BMSC administration can regulate the
expression of IL-4 and RAGE in the rats subjected to MODS. Moreover, BMSC can
promote the restoration of tissue and organ function, thus improve the survival
rate. BMSC may be the target in cell therapy for the inflammatory disease.
PMID- 28420461
TI - [alpha7 nicotinic acetylcholine receptor agonist attenuated the
lipopolysaccharide-induced inflammatory response via inhibiting the activation of
nuclear factor-KappaB].
AB - OBJECTIVE: To investigate the effects of alpha7 nicotinic acetylcholine receptor
(alpha7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in
RAW264.7 macrophages and its molecular mechanisms. METHODS: RAW264.7 macrophages
were cultured in vitro. Inflammatory cell model was constructed by LPS
stimulation. Cells were challenged by LPS (1, 10, 100 and 500 MUg/L) for 5 hours
or 100 MUg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of
tumor necrosis factor-alpha (TNF-alpha) was detected by the enzyme linked
immunosorbent assay (ELISA). The location of alpha7nAChR was examined in RAW264.7
macrophages by immunofluorescence. Then the cell proliferation and toxicity kit
(CCK-8) was used to detect 1, 10, 100, 1?000 MUmol/L GTS-21, a alpha7nAchR
agonist, on the cell viability after LPS stimulation. ELISA was used to detect 1,
10, 100, 1?000 MUmol/L GTS-21 on the levels of TNF-alpha, interleukin 1beta (IL
1beta) after LPS stimulation. Cells were challenged with 100 ?g/L LPS and 100
?mol/L GTS-21, then, the level of high mobility group box 1 (HMGB1) was detected
by Western Blot and the intracellular location of HMGB1 and nuclear factor-KappaB
p65 (NF-KappaB p65) was tested by immunofluorescence. RESULTS: LPS increased the
level of TNF-alpha to a peak at the concentration of 100 MUg/L and at 24 hours
after stimulation. The alpha7nAChR expressed on the macrophages. The cell
viability was decreased in a dose-dependent manner [(96.2+/-1.0)%, (92.0+/-1.1)%
vs. (86.5+/-2.2)%, both P < 0.05]. Compared with the control group, the levels of
TNF-alpha and IL-1beta in the supernatant of LPS group were significantly
increased [TNF-alpha (ng/L): 453.0+/-60.6 vs. 100.8+/-3.2, IL-1beta (MUg/L):
8.21+/-0.31 vs. 0.87+/-0.16, both P < 0.05]. TNF-alpha and IL-1beta were
significantly decreased by 10 MUmol/L and 100 MUmol/L GTS-21 in a dose-dependent
manner [TNF-alpha (ng/L): 227.5+/-17.5, 81.0+/-8.8 vs. 453.0+/-60.6; IL-1beta
(MUg/L): 4.86+/-0.72, 2.32+/-0.45 vs. 8.21+/-0.31, all P < 0.05]. GTS-21
significantly reduced the expression of HMGB1 which was induced by LPS management
(gray value: 0.788+/-0.130 vs. 2.061+/-0.330, P < 0.05) and reversed LPS-induced
HMGB1 cytoplasmic transfer. GTS-21 also reversed LPS-induced nuclear
translocation of NF-KappaB p65. CONCLUSIONS: GTS-21 reduces the inflammatory
response via inhibiting the activation of NF-KappaB.
PMID- 28420462
TI - [Differential expression profile of long non-coding RNA in the lipopolysaecharide
induced inflammation of monocyte-derived macrophages].
AB - OBJECTIVE: To analyze the expression profile of long non-coding RNA (lncRNA) in
the lipopolysaecharide (LPS)-induced inflammation of monocyte-derived
macrophages. METHODS: Peripheral blood mononuclear cells were derived from
healthy donor and induced into macrophages. The macrophages were divided into
blank control group and LPS (1 mg/L) stimulated 12 hours group. Culture
supernatants and cell pellets were harvested in each group, enzyme linked
immunosorbent assay (ELISA) was used to assay the production changes of
interleukins (IL-1beta and IL-6), and tumor necrosis factor-alpha (TNF-alpha) in
the supernatant. The technique of lncRNA microarray was used to test the lncRNA
expression profile in LPS-induced inflammation of macrophages and control
macrophages. The raw data of lncRNA were pretreated for normalization. Five
lncRNA expressions were validated by real-time quantitative reverse transcription
polymerase chain reaction (qRT-PCR). Furthermore, qRT-PCR was used to detect the
expression of NR_028034 in macrophages after LPS-induced inflammation. RESULTS:
(1) The contents of IL-1beta (ng/L: 562.93+/-61.17 vs. 59.74+/-15.68), IL-6
(ng/L: 702.46+/-92.31 vs. 71.66+/-18.25) and TNF-alpha (ng/L: 794.50+/-63.89 vs.
85.12+/-22.07) in the LPS group were significantly higher than those in the blank
control group (all P < 0.01). These results indicated that the inflammatory model
of human macrophages was constructed successfully. (2) Compared with blank
control group, and 1 479 lncRNA which have more than 2 folds variation and
significant difference (P < 0.05) by statistical analysis was defined as lncRNA
with differential expression. Among these lncRNA, LPS group showed 953 up-
regulated and 526 down- regulated genes by 2 folds and 49 up- regulated and 35
down- regulated genes by 5 folds. (3) qRT-PCR results were generally consistent
with the microarray data. (4) The expression of NR_028034 was increased by
(4.41+/-0.65), (11.56+/-2.04), (18.58+/-1.36) folds compared with blank control
group at 3, 6, 12 hours after LPS stimulation (all P < 0.01). CONCLUSIONS: These
data show a significantly altered lncRNA expression profile in the LPS-induced
inflammation of monocyte-derived macrophages, suggesting that lncRNA may be
involved in regulation of macrophages inflammatory response.
PMID- 28420463
TI - [Changes of small intestinal villi microcirculation in sidestream dark-field
imaging with different target blood pressure in rabbits during endotoxin shock].
AB - OBJECTIVE: Changes of small intestine villus microcirculation perfusion in
sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after
fluid resuscitation with different target mean arterial pressure (MAP), and
evaluation of feasibility of monitoring small intestine villus microcirculation
by SDF were studied. METHODS: Sixty standard New Zealand white rabbits were
randomly divided into two groups: low target MAP group (group A, n = 30) and high
target MAP group (group B, n = 30). Fistula operation of ileum was made in vitro,
and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock
model. Group A was administered with the lower dose fluid resuscitation (lactated
Ringer solution, 20 mL*kg-1*h-1) for target MAP of 65 mmHg (1 mmHg = 0.133 kPa);
group B was administered with the higher dose fluid resuscitation (lactated
Ringer solution, 30 mL*kg-1*h-1) for MAP of 80 mmHg. Continuous norepinephrine
intravenous injection (0.5-1.0 MUg*kg-1*min-1) was administered only after fluid
therapy couldn't reach the target MAP. The changes of small intestine villus
microcirculation perfusion indexes such as vessels per villus (VV), proportion of
perfused villi (PPV), microvascular flow index (MFI), borders of villus score
(BVS), vessels villus score (VVS) were continuously observed and recorded before
the shock, during the shock and after fluid resuscitation using SDF imaging. The
differences of microcirculation perfusion were compared between two groups using
the specific parameter evaluation system to determine severity of villi
microcirculation and injury scores at different stages. RESULTS: VV and borders
of villus were clear and contact before shock in two groups. After shock, VV, PPV
were significantly decreased in both two groups, the borders of villus were
destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation
were obviously and severely decreased. Partial blood flow of villous capillaries
after fluid resuscitation was recovered in two groups, but the perfusion of some
region was un-balanced with the outworn borders of villus. VV were rose as
compared before and after fluid resuscitation in groups A and B (vessels: 1.21+/
0.22 vs. 0.81+/-0.12, 1.54+/-0.28 vs. 0.79+/-0.13), and PPV [(31+/-4)% vs. (12+/
2)%, (38+/-5)% vs. (13+/-3)%], MFI (1.55+/-0.09 vs. 1.09+/-0.03, 1.97+/-0.11 vs.
1.05+/-0.03), VVS (points: 1.22+/-0.08 vs. 0.89+/-0.02, 2.06+/-0.15 vs. 0.90+/
0.02) and the sum of MFI, BVS, VVS (3.70+/-0.19 vs. 2.85+/-0.07, 5.01+/-0.29 vs.
2.88+/-0.08) were significant rose (all P < 0.05). The recovery of group B was
better than that of group A, and the injury score was reduced. But BVS were not
increased in both groups compared with before and after shock (points: 0.93+/
0.05 vs. 0.87+/-0.03, 0.98+/-0.09 vs. 0.93+/-0.05, both P > 0.05). CONCLUSIONS:
For the small intestine villus microcirculation perfusion, the higher target MAP
(80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were
probably better than the relatively lower target MAP (65 mmHg) during endotoxic
shock. SDF imaging is a very promising technique for intestinal villi
microcirculatory visualization and assessment.
PMID- 28420464
TI - [Effect of combination therapy with propofol and hydrogen-rich saline on organ
damage and cytokines in a murine model of sepsis].
AB - OBJECTIVE: To investigate the effect of combining propofol with hydrogen on organ
damage and inflammation of sepsis in cecal ligation and puncture (CLP) mice
model. METHODS: One hundred and forty male C57BL/6 mice were randomly divided
into groups (n = 28): sham group, CLP group, propofol group, H2 group, and
propofol and H2 group. The sepsis was induced by CLP operation. Mice in sham
group did the same operation with ligation and puncture. The mice of propofol
group and propofol and H2 group were given 50 mg/kg propofol through tail vein at
1 hour and 6 hours after CLP and the mice of H2 group and propofol and H2 group
were given 5 mL/kg H2-rich saline i.p. at 1 hour and 6 hours after CLP. The
survival rates were observed during 7 days in twenty mice of each group. Inferior
vena cava blood and part lung, liver and kidney tissue were collected for
detection of the concentration of tumor necrosis factor-alpha (TNF-alpha),
interleukin-1beta (IL-1beta) and high mobility group box 1 (HMGB1) at 24 hours
after CLP in the 40 animals left (each n = 8). Then, the rest tissue of lung,
liver and kidney tissue were harvested to test histopathology and histological
score. RESULTS: The 1, 2, 3, 5, 7 days survival rate of septic mice were 80%,
40%, 20%, 10%, and 0%, respectively. The survival rate of animals increased
significantly after propofol or hydrogen-rich treatment, and the combined
treatment can further increase survival rate to 90%, 75%, 60%, 55%, and 55%,
respectively. Compared with the sham group, inflammatory factors were
significantly increased in blood and organ tissues, cell degeneration, necrosis,
congestion and inflammatory cell infiltration in lung, liver and kidney, and
tissues histological scores were significantly increased. The levels of
inflammatory factors were reduced in blood and tissues, cell degeneration,
necrosis, congestion and inflammatory cell infiltration were alleviated in lung,
liver and kidney, and tissues histological scores were decreased after propofol
or hydrogen-rich treatment compared with CLP group; these indicators were further
improved in propofol and H2 group compared with propofol group or H2 group [2, 3,
5, 7-day survival rate: 75% vs. 60%, 65%; 60% vs. 50%, 50%; 55% vs. 45%, 40%; 55%
vs. 40%, 40%; blood TNF-alpha (ng/L): 367+/-74 vs. 612+/-132, 588+/-117; blood IL
1beta (ng/L): 321+/-68 vs. 502+/-95, 476+/-86; blood HMGB1 (MUg/L): 4.6+/-0.9 vs.
7.0+/-1.4, 6.8+/-1.3; lung TNF-alpha (ng/g): 307+/-70 vs. 512+/-132, 488+/-102;
lung IL-1beta (ng/g): 367+/-77 vs. 571+/-108, 466+/-89; lung HMGB1 (MUg/g): 5.1+/
1.0 vs. 7.8+/-1.7, 7.1+/-1.5; liver TNF-alpha (ng/g): 247+/-57 vs. 431+/-112,
389+/-87; liver IL-1beta (ng/g): 267+/-58 vs. 417+/-85, 399+/-76; liver HMGB1
(MUg/g): 4.2+/-1.1 vs. 7.1+/-1.6, 6.6+/-1.2; kidney TNF-alpha (ng/g): 257+/-41
vs. 480+/-89, 448+/-82; kidney IL-1beta (ng/g): 258+/-39 vs. 409+/-68, 411+/-66;
kidney HMGB1 (MUg/g): 3.9+/-0.7 vs. 6.8+/-1.2, 5.7+/-1.0; histological scores:
lung: 1.22+/-0.28 vs. 2.61+/-0.49, 2.58+/-0.44; liver: 1.38+/-0.32 vs. 2.76+/
0.51, 2.62+/-0.46; kidney: 1.19+/-0.25 vs. 2.43+/-0.41, 2.36+/-0.40; all P <
0.05]. CONCLUSIONS: Both propofol and H2 can improve the survival rate of sepsis,
reduce tissue damage and the release of cytokines, and combined application of
the two treatment was better.
PMID- 28420465
TI - [Clinical value of serum endocan and procalcitonin in early diagnosis and
prognosis evaluation of sepsis].
AB - OBJECTIVE: To investigate the clinical value of serum endocan and procalcitonin
(PCT) in early diagnosis and prognosis evaluation of sepsis. METHODS: The
patients with systemic inflammatory response syndrome (SIRS, n = 26) and sepsis
(n = 78) admitted to intensive care unit (ICU) of the Third Hospital of Hebei
Medical University from December 2014 to December 2016 were enrolled. According
to the severity of disease, the sepsis patients were divided into general sepsis
group (n = 20), severe sepsis group (n = 24), and septic shock group (n = 34).
The cases were divided into survival group (n = 55) and non-survival group (n =
23) according to 28-day mortality. The serum endocan, PCT, acute physiology and
chronic health evaluation II (APACHEII) score, and sequential organ failure
assessment (SOFA) score were recorded when the patients were admitted into ICU.
The differences in endocan, PCT, APACHEII, SOFA score between SIRS and sepsis
groups and within sepsis subgroups were compared. Spearman correlation analysis
was used to analyze the correlation between the indexes of sepsis patients.
Receiver operation characteristic curve (ROC) was used to evaluate the value of
endocan and PCT for the diagnosis and prognosis of sepsis. RESULTS: (1) Serum
endocan, PCT, APACHEII, SOFA score and 28-day mortality in the sepsis group were
significantly higher than those in the SIRS group [endocan (MUg/L): 4.28 (10.64)
vs. 1.03 (0.69), PCT (MUg/L): 3.94 (10.75) vs. 0.43 (0.39), APACHEII: 18.81+/
9.17 vs. 9.35+/-3.78, SOFA: 9.00 (7.20) vs. 4.50 (1.50), 28-day mortality: 29.49%
vs. 11.54%, all P < 0.01]. The area under the ROC curve (AUC) of endocan, PCT,
APACHEII, SOFA score for sepsis diagnosis were 0.887, 0.842, 0.822, 0.835,
respectively. When the cut-off value of endocan was 1.26 MUg/L, the sepsis
diagnostic sensitivity was 87.2% and specificity was 81.8%. When the cut-off
value of PCT was 0.75 MUg/L, the sepsis diagnostic sensitivity was 85.9% and
specificity was 81.8%. (2) With the severity of the disease increased, the index
showed an increasing trend in patients with sepsis. Serum endocan, PCT, APACHEII,
SOFA score and 28-day mortality in septic shock group were significantly higher
than those in severe sepsis group or general sepsis group [endocan (MUg/L): 13.02
(6.70) vs. 3.33 (3.05), 1.60 (0.98); PCT (MUg/L): 8.10 (17.68) vs. 5.47 (8.92),
1.57 (2.78); APACHEII: 25.00 (9.50) vs. 18.00 (9.00), 9.50 (5.75); SOFA: 13.00
(4.50) vs. 8.00 (3.00), 5.00 (3.50); 28-day mortality: 52.94% vs. 20.83%, 0%; all
P < 0.01]. There was a significantly positive correlation between endocan, PCT,
APACHEII, SOFA, indicating that the endocan and PCT can be used to assess the
severity of sepsis. (3) Serum endocan, PCT, APACHEII and SOFA score in non
survival group were significantly higher than those in the survival group
[endocan (MUg/L): 15.05 (9.23) vs. 2.32 (4.81), PCT (MUg/L): 18.40 (16.99) vs.
3.10 (6.67), APACHEII: 28.13+/-7.56 vs. 14.91+/-6.64, SOFA: 14.70+/-3.65 vs.
7.38+/-3.26, all P < 0.01]. The AUC of endocan, PCT, APACHEII, SOFA score for the
prediction of non-survival sepsis were 0.915, 0.763, 0.899, 0.930. When the cut
off value of endocan was 4.37 MUg/L, the septic death prediction sensitivity was
95.7% and specificity was 70.9%. When the cut-off value of PCT was 7.68 MUg/L,
the septic death prediction sensitivity was 65.2% and specificity was 78.2%.
CONCLUSIONS: Serum endocan is more clinically valuable than PCT in early
diagnosis and prognosis assessment of sepsis.
PMID- 28420466
TI - [Analysis of evaluation indexes for prognosis of severe burn patients with
sepsis].
AB - OBJECTIVE: To compare changes in indexes and analyze their values in prognosis of
severe burn patients with sepsis. METHODS: A retrospective analysis was
conducted. The patients with severe burn sepsis admitted to the Third Affiliated
Hospital of Soochow University from August 2014 to December 2016 were enrolled.
The blood culture was positive in the clinical diagnosis of sepsis. According to
the prognosis, the patients were divided into death group and survival group.
Their general information, vital signs, blood routine examination, serum sodium
(Na+), serum glucose (Glu), C-reactive protein (CRP) and arterial partial
pressure of carbon dioxide (PaCO2) at the time of admission and diagnosis of
sepsis as well as the level of serum procalcitonin (PCT) at admission, diagnosis
of sepsis and 1-8 days of post diagnosis were also compared. Receiver operating
characteristic curve (ROC) was used to analyze the prognostic value of each
index, and multivariate Cox regression analysis was used to analyze the influence
of each index on the survival time, and the survival curve of Kaplan-Meier was
analyzed for dead patients. RESULTS: There were 25 cases of severe burn patients
with sepsis, which were admitted to hospital within 12 hours after injury; the
time of diagnosis of burn sepsis was (14+/-6) days; 8 cases of survival; 17 cases
died, the mortality rate was 68.0%, the time from diagnosis of sepsis to death
was (28+/-14) days. The age of the death group was significantly higher than that
of the survival group (years: 41+/-12 vs. 29+/-9, t = 2.598, P = 0.016), but
there was no significant difference in the gender, total burn area, III degree
area, and the time of diagnosis of sepsis between the two groups. The platelet
count (PLT) at the diagnosis of sepsis in death group was significantly lower
than that of the survival group (*109/L: 69+/-43 vs. 180+/-108, t = -2.773, P =
0.023), and the PCT at 1-8 days of post-diagnosis in the death group was
significantly higher than that of survival group [MUg/L: 4.4 (2.2, 9.0) vs. 1.6
(0.7, 2.3), Z = -2.521, P = 0.012], but there was no significant difference in
body temperature, heart rate, white blood cell count (WBC), percentage of
neutrophils (Neu), Na+, Glu, CRP, PCT, PaCO2 at the time of admission and
diagnosis of sepsis and PLT at the time of admission between the two groups. ROC
curve analysis showed that the area under ROC curve (AUC) of age, PLT at the time
of diagnosis and PCT at 1-8 days of post-diagnosis of sepsis was 0.808, 0.779,
0.825, respectively, for predicting the prognosis of patients with severe burn
sepsis (all P < 0.05). At the cut-off age of 32, the sensitivity was 73.3% and
the specificity was 75.0%. As the cut-off of PLT was 138*109/L at the time of
diagnosis, the sensitivity was 92.3% and the specificity was 75.0%. As the cut
off of PCT was 2.39 MUg/L at 1-8 days of post-diagnosis of sepsis, the
sensitivity was 73.3% and the specificity was 87.5%. Multivariate Cox regression
analysis showed that age and PLT at the time of diagnosis were the favorable
factors for the survival time of patients with severe burn sepsis (beta value
were -1.834, -0.029, respectively, both P < 0.05). Kaplan-Meier survival analysis
for patients in the death group showed that the median survival time of patients
>=32 years old was longer than that of patients < 32 years old (days: 32 vs. 9);
18-day cumulative survival rate was significantly higher than that of patients <
32 years old [83.3% (10/12) vs. 25.0% (1/4), chi 2 = 9.705, P = 0.003].
CONCLUSIONS: Age, PLT at diagnosis of sepsis and PCT at 1-8 days after diagnosis
of sepsis could be used as prognostic indexes for severe burn patients with
sepsis.
PMID- 28420467
TI - [Study of Plasma amino acid related metabolites of septic rats using gas
chromatography-mass spectrometry].
AB - OBJECTIVE: To reveal the pathophysiological changes of sepsis, the plasma
metabonomics of septic rats was determined and differential metabolites were
determined by gas chromatography-mass spectrometry (GC-MS). METHODS: Male
Spraguee-Dawley (SD) rats about 8 weeks were randomly divided into sham group (n
= 18) and sepsis group (n = 24). Cecal ligation and puncture (CLP) was used to
build sepsis model, while cecum was kept intact only in the sham group. 6 hours
after the operation, rats were anesthetized, and blood was harvested through
heart thoracotomy. Then the plasma metabonomics was detected by GC-MS and
metabolic profile analysis was performed to find the relative differential
metabolites. RESULTS: Principal component analysis (PCA) and partial least
squares discriminant analysis (PLS-DA) showed that the metabolic profiling of the
sepsis group was significantly different from the sham group. 259 kinds of
metabolites were got by GC-MS, and 69 kinds of differential metabolites were
found between sham group and sepsis group, in which 23 differential metabolites
were related to amino acid metabolism. Compared with sham group, the contents of
putrescine, N-glutamic acid, hydroxynorvaline, 3-cyanuric acid, D-alanyl-D
alanine and urea in the plasma of septic rats increased significantly, which
ratios of sepsis/sham group were 10.876, 6.394, 2.800, 2.226, 1.323, 1.203,
respectively (all P < 0.05). On the other hand, the contents of oxygen generation
of proline, citrulline, glutamine, su-beta-hydroxy aspartic acid, citric acid, N
methyl-DL-alanine, serine, lysine, threonine, N-formyl-L-methionine, methionine,
alanine, nicotinuric acid, N-methyl-L-glutamic acid, trans-4-hydroxy-L-proline,
proline, L-glutamic acid in the plasma of septic rats decreased significantly,
which ratios of sepsis/sham group were 0.858, 0.853, 0.834, 0.816, 0.816, 0.814,
0.813, 0.801, 0.793, 0.792, 0.774, 0.766, 0.748, 0.727, 0.716, 0.674, 0.603,
respectively (all P < 0.05). CONCLUSIONS: Through the GC-MS analysis of plasma
metabonomics of septic rats, we found abnormal energy metabolism changes. The
content of amino acid in plasma might be a method to evaluate the energy
metabolism status of sepsis.
PMID- 28420468
TI - [Effect of heparin pretreatment on the level of neutrophil extracellular traps of
serum and lung tissue in septic mice].
AB - OBJECTIVE: To investigate the influence of heparin pretreatment on serum and lung
tissue level of neutrophil extracellular traps (NETs) in septic mice model and
its molecular mechanism. METHODS: Ninety male C57BL/6J mice were randomly divided
into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg
LPS in 100 ?L normal saline was intraperitoneally injected) and LPS+heparin group
(n = 30, 8 U of heparin in 20 ?L normal saline was subcutaneously injected 30
minutes before the injection of LPS). Six hours later of LPS injection, blood was
collected and lung tissue was harvested. Enzyme linked immunosorbent assay
(ELISA) was used to assess the concentration of tumor necrosis factor-alpha (TNF
alpha), interleukin-6 (IL-6), and histones 2AX (H2AX), neutrophil elastase (NE),
which reflected NETs concentration. PicoGreen fluorescent dyes was used to detect
serum circulating free DNA (cf-DNA/NETs) concentration. The protein expression
levels of H2AX and NE in lung tissue were examined by Western Blot. RESULTS: The
serum concentrations of TNF-alpha, IL-6, H2AX, NE, cf-DNA/NETs, and the protein
expression levels of H2AX and NE in lung tissue of septic mice were significantly
higher than those of control group [TNF-alpha (ng/L): 133.0+/-14.1 vs. 2.7+/-1.0,
IL-6 (ng/L): 3 911.2+/-189.2 vs. 298.9+/-52.5, H2AX (ng/L): 545.5+/-40.0 vs.
21.9+/-8.3, NE (MUg/L): 6.48+/-0.12 vs. 0.47+/-0.15, cf-DNA/NETs (MUg/L): 846.3+/
137.5 vs. 152.7+/-36.4, H2AX protein (gray value): 1.14+/-0.09 vs. 0.68+/-0.04,
NE protein (gray value): 0.56+/-0.03 vs. 0.32+/-0.04, all P < 0.05]. After
heparin pretreatment, levels of serum TNF-alpha, H2AX, NE, cf-DNA/NETs, and
protein expression levels of H2AX and NE in lung tissue were significantly
reduced [TNF-alpha (ng/L): 83.2+/-7.6 vs. 133.0+/-14.1, H2AX (ng/L): 435.0+/-39.0
vs. 545.5+/-40.0, NE (MUg/L): 4.26+/-0.17 vs. 6.48+/-0.12, cf-DNA/NETs (MUg/L):
606.5+/-73.9 vs. 846.3+/-137.5, H2AX protein (gray value): 0.91+/-0.03 vs. 1.14+/
0.09, NE protein (gray value): 0.42+/-0.03 vs. 0.56+/-0.03, all P < 0.05], but no
significant change was found in IL-6 (ng/L: 3 919.9+/-166.6 vs. 3 911.2+/-189.2,
P > 0.05). CONCLUSIONS: Heparin pretreatment could significantly decrease the
level of NETs in serum and lung tissue, and can be the potential mechanism of its
organ protection in sepsis.
PMID- 28420469
TI - [Heparin reduces endothelial cell damage induced by neutrophil extracellular
traps].
AB - OBJECTIVE: Clarify the effect of neutrophil extracellular traps (NETs) on
endothelial cell injury, and investigate whether the heparin can exert a
protective effect on endothelial cells by reducing the endothelial cell injury
induced by NETs. METHODS: Neutrophils (PMN) were obtained from healthy human
peripheral blood by Percoll-Histopaque density gradient centrifugation, and was
stimulated with phorbol ester (PMA) to induce NETs. The qualitative and
quantitative analysis of NETs was detected by immunofluorescence staining
combined with fluorescence detector. The NETs were used to induce human umbilical
vein endothelial cells (HUVEC) in vitro. Recombinant DNA hydrolytic enzymes
(rhDNase) and heparin intervention were added respectively. The activity of HUVEC
was measured by methyl thiazolyl tetrazolium (MTT) method after 6 hours. RESULTS:
PMA can stimulate PMN to produce NETs. Immunofluorescence staining showed the
formation of reticular formation around the PMN. The concentration of cell-free
DNA in the supernatant of PMN stimulated by PMA was significant increased
compared with the control group through the detection of PicoGreen fluorescent
labeling instrument (2 hours: 119.62+/-14.83 vs. 24.27+/-0.67, 4 hours: 146.67+/
21.24 vs. 28.35+/-2.98, both P < 0.05). Application of NETs to stimulate the
HUVEC, cell damage was dose dependent and inhibition rate increased gradually.
The endothelial cell inhibition induced by NETs can be antagonized after adding
rhDNase [10 MUg/L NETs: (8.65+/-0.51)% vs. (10.99+/-0.35)%, 20 MUg/L NETs:
(14.85+/-0.43)% vs. (16.85+/-0.49)%, 30 MUg/L NETs: (26.06+/-3.51)% vs. (27.54+/
0.62)%, all P < 0.05]. Heparin with different concentrations were added into the
experimental group (0.01, 0.1, 1, 10 kU/L). We found that the endothelial cell
inhibition rate decreased compared with control group [10 MUg/L NETs: (8.96+/
0.70)%, (5.32+/-1.36)%, (0.70+/-0.30)%, (0.75+/-0.20)% vs. (10.99+/-0.35)%; 20
MUg/L NETs: (15.57+/-0.62)%, (13.28+/-0.65)%, (6.91+/-0.15)%, (5.86+/-0.17)% vs.
(16.85+/-0.49)%; 30 MUg/L NETs: (30.49+/-0.74)%, (29.41+/-1.41)%, (23.45+/
0.75)%, (21.72+/-1.52)% vs. (27.54+/-0.62)%, all P < 0.05]. CONCLUSIONS: NETs can
induce endothelial cell injury, and the injury degree was increased with the
concentration of NETs. Heparin can reduce endothelial cell injury induced by
NETs, which may be a potential mechanism for the protective effect of heparin on
sepsis.
PMID- 28420470
TI - [Explore objective clinical variables for detecting delirium in ICU patients: a
prospective case-control study].
AB - OBJECTIVE: The aim of this case-control study is to explore clinical objective
variables for diagnosing delirium of intensive care unit (ICU) patients. METHODS:
According to the method of prospective case-control study, critical adult
postoperative patients who were transferred to ICU of Peking University People's
Hospital from October 2015 to May 2016 and needed mechanical ventilation were
included. After evaluating the Richmond agitation sedation scale score (RASS),
the patients whose score were -2 or greater were sorted into two groups, delirium
and non-delirium, according to the confusion assessment method for the ICU (CAM
ICU). Then these patients were observed by domestic multifunctional detector for
electroencephalographic (EEG) variables such as brain lateralization, brain
introvert, brain activity, brain energy consumption, focus inward, focus outward,
cerebral inhibition, fatigue, sleep severity, sedation index, pain index, anxiety
index, fidgety index, stress index and the cerebral blood flow (CBF) index which
was named of perfusion index. Other variables including indexes of ICU blood gas
analysis, which was consisted of variables of blood gas analysis, routine blood
test and biochemistry, previous history and prognostic outcome was recorded.
Binary logistic regression was used for multivariate analysis. RESULTS: Forty
three postoperative patients, who needed intensive care, were included. Eighteen
were in delirium group and twenty-five in control group. Excluding the trauma,
variables like gender, age, temperature, heart rate, respiratory rate, mean
arterial pressure, acute physiology and chronic health evaluationII(APACHEII)
score, organ failure, dementia and emergency surgery didn't show any statistical
significance between two groups. The trauma in delirious patients increased
obviously compared with the control group (33.3% vs. 4.0%, P = 0.031). Except for
the brain activity [122.47 (88.62, 154.21) vs. 89.40 (86.27, 115.97), P = 0.034],
there were no statistical differences in any other EEG and CBF variables. In ICU
blood gas analysis, only pH value (7.43+/-0.42 vs. 7.47+/-0.31, P = 0.003),
chloride concentration [Cl- (mmol/L): 114.66+/-4.32 vs. 111.90+/-3.08, P =
0.019], magnesium concentration [Mg2+ (mmol/L): 0.60+/-0.10 vs. 0.54+/-0.06, P =
0.035] and blood osmolality [mmol/L: 290.10 (284.15, 306.35) vs. 282.70 (280.20,
286.75), P = 0.014] were statistically significant. Compared with control group,
the prognostic variables in delirium group such as duration of mechanical
ventilation [days: 125.0 (49.0, 293.0) vs. 149.5 (32.0, 251.3)], length of stay
in ICU [days: 216.5 (50.5, 360.8) vs. 190.0 (72.0, 330.5)] and mortality rate
(22.2% vs. 24.0%) didn't appear to be statistically significant either (all P >
0.05). It was shown by multivariate logistic regression analysis that pH [odds
ratio (OR) = 1.446, 95% confidence interval (95%CI) = 1.116-1.875, P = 0.005] and
Cl- (OR = 0.708, 95%CI = 0.531-0.945, P = 0.019) were potential risk factors of
delirium. CONCLUSIONS: The brain activity of HXD_I may contribute to the clinical
diagnose of delirium, but it still remained to be proved further. The pH and Cl-
are potential risk factors of delirium.
PMID- 28420471
TI - [Mixed venous-arterial carbon dioxide difference combined with passive leg
raising in guiding volume management for patients post off-pump coronary artery
bypass grafting].
AB - OBJECTIVE: To investigate whether mixed venous-arterial carbon dioxide difference
(Pv-aCO2) combined with passive leg raising (PLR) could better guide volume
management for patients post off-pump coronary artery bypass grafting (OPCABG).
METHODS: Eighty patients experienced OPCABG, and admitted to Tianjin Chest
Hospital from June 1st to October 1st in 2016 were enrolled. They were randomly
divided into two groups: observation group given Pv-aCO2 combined with PLR
directed therapy and control group given central venous pressure (CVP) directed
therapy, 40 cases in each group. The difference in body temperature (T), heart
rate (HR), mean arterial pressure (MAP), CVP, oxygenation index (PaO2/FiO2),
mixed venous oxygen saturation (SvO2), Pv-aCO2, blood lactate (Lac), fluid
intake, scores of the vasoactive agents at 6 hours post-operation, sequential
organ failure assessment (SOFA) of 24 hours, mechanical ventilation time, the
length of intensive care unit (ICU) stay, and hospitalization time were compared.
The correlation between Pv-aCO2 and cardiac index (CI), Pv-aCO2 and Lac were
analyzed by Spearman analysis in observation group. RESULTS: The T, HR, MAP, CVP,
PaO2/FiO2, SvO2 and Lac at 6 hours post-operation were higher than those at
admission in two groups, and Pv-aCO2 were significantly decreased. The SvO2 and
fluid intake in observation group were higher than those in control group [SvO2:
0.671+/-0.068 vs. 0.634+/-0.052, fluid intake (mL): 454+/-151 vs. 304+/-106, both
P < 0.05], Pv-aCO2, Lac and scores of the vasoactive agents were lower than those
in control group [Pv-aCO2 (mmHg, 1 mmHg = 0.133 kPa): 6.1+/-1.8 vs. 7.0+/-1.8,
Lac (mmol/L): 1.7+/-0.5 vs. 2.8+/-0.6, scores of the vasoactive agents: 3.18+/
1.01 vs. 4.48+/-1.50, all P < 0.05], mechanical ventilation time and the length
of ICU stay were less than those in the control group (hours: 16.52+/-6.41 vs.
21.96+/-9.00, 45.51+/-9.36 vs. 51.76+/-13.66, both P < 0.05). There was no
significant difference in SOFA, hospitalization time between the two groups.
There was negative correlation with Pv-aCO2 and CI (r = -0.752, P < 0.01), and no
correlation with Pv-aCO2 and Lac (r = -0.154, P = 0.171). CONCLUSIONS: Pv-aCO2
combined with PLR can better guide volume management in the patients post OPCABG,
reduce the usage of vasoactive agents and decrease the mechanical ventilation
time and the length of ICU stay.
PMID- 28420472
TI - [Analysis of the onset time of acute aortic dissection and the influence of
climate on acute aortic dissection occurrence in Urumqi city: a retrospective
study of a single center].
AB - OBJECTIVE: To observe the time characteristics of acute aortic dissection (AAD)
in Urumqi and its peripheral areas in Xinjiang Uygur autonomous region, and to
explore the effect of meteorological conditions on the onset of AAD. METHODS:
Retrospective analysis of the related data of the adult AAD patients diagnosed by
imaging examination, and admitted to the First Affiliated Hospital of Xinjiang
Medical University from March 2010 to July 2016 was performed. The onset time,
the contemporaneous meteorological data, including daily minimum, average, and
the highest temperature, daily average air pressure, daily average relative
humidity, daily precipitation, daily average wind speed, daily maximum wind
speed, and sunshine duration per day were collected. Analysis of concentrated
distribution trend of the AAD onset was done by circular distribution statistics.
Meteorological conditions were compared between "the AAD day" and "no AAD day".
The changes of air temperature 5 days before onset were observed. RESULTS: A
total of 379 patients were enrolled, with 307 male and 72 female. The ratio of
male to female was 4.19: 1, the average age was 52.27+/-12.18; and the underlying
diseases was hypertension (about 58.05%); the incidence sites were Urumqi and
Changji city. (1) The incidence of AAD in Urumqi and its peripheral areas had
clear concentrated trend, and the peak period of AAD corresponded to January 1st
to 2nd (homogeneity test r = 0.104, r 0.05 = 0.009, P < 0.05). (2) The minimum,
mean and maximal atmospheric temperatures on "the AAD day" were lower than "no
AAD day" [centigrade: 4.10 (-9.55, 14.60) vs. 7.75 (-6.70, 16.20), 14.10 (-1.50,
25.00) vs. 17.50 (0.60, 26.78), 8.50 (-6.22, 19.45) vs. 12.10 (-3.60, 20.90), all
P < 0.05], sunshine duration was significantly shorter than "no AAD day" [hours:
8.50 (4.60, 10.70) vs. 8.90 (5.50, 11.50), P < 0.01], and atmospheric pressure
were higher than "no AAD day" [kPa: 91.24 (90.66, 91.75) vs. 91.12 (90.62,
91.61), 19.11 (18.99, 19.22) vs. 19.09 (18.98, 19.19), both P < 0.05]; there were
no significant differences in the incidence of daytime temperature difference,
average relative humidity, precipitation, average wind speed, and maximum wind
speed between the two groups. (3) the peak period of AAD occurrence was December
(38 cases), which was followed by January (36 cases); and there were 26 cases of
each month in May, June, July, and September, which were lower than the rest of
months. It was shown by the temperature distribution that the minimum average
temperature was in January (-12.46 centigrade), followed by December (-9.03
centigrade); the maximum average temperature was in July [(24.59+/
3.21)centigrade], followed by August [(23.14+/-3.64)centigrade]. (4) The patients
was sorted according to the quartile of daily mean temperature, into < -5.2
centigrade, -5.2-10.7 centigrade, 10.7-20.4 centigrade, and > 20.4 centigrade
groups, and each group had 104, 99, 98, 78 cases of AAD, respectively. The number
of AAD in lowest temperature group was 1.33 times of the highest temperature
group. In the 45-59 and 60-74 years, the number of AAD in lowest temperature
group was higher than that in the highest temperature group (50 vs. 36, 26 vs.
13). In patients with hypertension, the number of AAD in lowest temperature group
was higher than that in the highest temperature group (60 vs. 44). (5) The
maximum air temperature, mean air temperature of the day from 5 days before to
the onset day of AAD, and the lowest temperature from 3 days before to the onset
day of AAD display slowly decrease trends, but there was no significant
difference in daily temperature. CONCLUSIONS: The incidence of AAD in Urumqi and
its peripheral areas was concentrated from January 1st to 2nd of each year. When
the temperature was lower than -5.2 centigrade, AAD were more likely to attack.
The 5 days changes of temperature and daily temperature before the attack were
relevant with onset of AAD. It was speculated that the weather conditions such as
air temperature may affect patient who has a past history of cardiovascular
disease to attack AAD.
PMID- 28420473
TI - [The study of serum complements and proinflammatory cytokines in sepsis rats].
AB - OBJECTIVE: To observe the changes of serum complements and proinflammatory
cytokines in rats with sepsis, and to explore the possible mechanism. METHODS:
120 healthy male Wistar rats were randomly divided into three groups: normal
control group (n = 15), sham operation group (n = 15) and sepsis group [cecum
ligation and puncture (CLP) operation, n = 90]. The sepsis rats were sacrificed
on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a)
and cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1, IL-6),
high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF)
were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared
with normal control group and sham operation group, the levels of serum
complements C5, C5a and IL-1beta were significantly increased at 24 hours after
CLP in sepsis group [C5 (ng/L): 1.60+/-0.19 vs. 1.04+/-0.20, 1.09+/-0.09; C5a
(ng/L): 0.20+/-0.02 vs. 0.18+/-0.01, 0.18+/-0.02; IL-1beta (ng/L): 700.20+/
111.41 vs. 475.87+/-108.96, 592.29+/-121.57; all P < 0.05]; then the levels of
C5, C5a and IL-1beta declined, the level of serum C5 were also higher than normal
control group at 48 hours and 72 hours after CLP (ng/L: 1.17+/-0.24, 1.27+/-0.24
vs. 1.04+/-0.20, both P < 0.05). In sepsis group the level of serum TNF-alpha
(ng/L: 51.33+/-1.96, 51.06+/-1.64) was lower than that in normal control group
(59.53+/-3.06) and sham operation group (57.91+/-2.72) at 48 hours and 72 hours
(all P < 0.05). There was a time dependent rise of serum HMGB1 in sepsis group,
which level was much higher than that in normal control group and sham operation
group at 72 hours after CLP (ng/L: 472.21+/-20.94 vs. 406.00+/-43.16, 404.41+/
35.39, both P < 0.05). There were no significant differences of MIF, and IL-6
level between groups at each time points. CONCLUSIONS: Complement system led to
uncontrolled inflammatory response and immune dysfunction through the release of
proinflammatory cytokines and inflammatory mediators, which maybe one of the
important mechanism of the pathology of sepsis.
PMID- 28420474
TI - [Value of APACHEIIfor predicting the nursing workload in EICU].
AB - OBJECTIVE: To investigate the predictive value of acute physiology and chronic
health evaluationII(APACHEII) for nursing workload in emergency intensive care
unit (EICU). METHODS: A retrospective cohort study was conducted. Critical
patients except for trauma admitted to EICU of West China Hospital of Sichuan
University from June 2012 to July 2016 were enrolled. APACHEII score and
therapeutic intervention scoring system (TISS-28) score were calculated in each
case. The relationship between APACHEIIscore and TISS-28 score was analyzed by
correlation analysis and curve estimation. RESULTS: A total of 1 148 patients
were enrolled, including 689 male (60.0%), and age of (56+/-19) years old,
APACHEII score was 19 (13, 25), and TISS score was 19 (13, 25). The Spearman
correlation coefficient between APACHEII score and TISS-28 score was 0.849 (P <
0.001), and that among the linear model quadratic model, composite model, growth
model, logarithm model, cubic model and exponential model R 2 were 0.669, 0.710,
0.792, 0.764, 0.765, 0.765, respectively (all P < 0.01), and the most suitable
description for relationship between APACHEIIscore and TISS-28 score curve was
cubic model. The nursing workload was significantly increased when APACHEII score
>=30, and it was decreased when APACHEII score < 30. CONCLUSIONS: APACHEIIwas a
useful score for predicting the nursing workload in EICU.
PMID- 28420475
TI - [Design and application of emergency rescue bag in pediatrics].
PMID- 28420476
TI - [Mechanism of resolvins in reducing the inflammation reaction in inflammatory
diseases].
AB - OBJECTIVE: Inflammation is an important mechanism for the host to resist external
infection and injury. Under normal conditions, adaptive inflammatory response not
only is conducive to the repair of damaged cells and tissues, but plays an
important role to promote the internal environment to restored homeostasis.
However, when the immune function is damaged, the unresolved and uncontrolled
inflammation will cause non-specific tissue damage, which is linked to a variety
of inflammatory diseases. In the acute inflammation, resolvins, a group of
endogenous small molecular lipid mediators which are biosynthesized by
polyunsaturated fatty acids, possess anti-inflammatory and pro-resolving actions,
which are benefit for the repair of damaged tissue. Therefore, it is helpful to
deeply explore the mechanisms of resolvins in inflammation-resolution phases of
acute lung injury (ALI) and sepsis, which are favor of understanding the complex
processes and provide new treatment for the inflammatory diseases thereby
reducing the mortality in the intensive care unit (ICU).
PMID- 28420477
TI - [Metabolism of high density lipoprotein and the research progress of its effects
on sepsis].
AB - OBJECTIVE: Sepsis is a high-risk factor for the death of critical patients. High
density lipoprotein (HDL) are the major protective serum proteins, and the serum
levels of HDL are closely related to the severity of sepsis. The anti
inflammatory and anti-oxidation properties of HDL, may be able to play an
important role in the innate immune response. Thereby it may reduce the damage of
septic shock and multiple organ dysfunction syndrome (MODS) in animals or human
beings, and improve the prognosis. In order to unveil the metabolism of HDL in
septic patients and its effects on both progression and prognosis of sepsis, this
review not only focuses on the composition and structure of HDL, but also
analyzes its pivotal role in inflammatory immune response and anti-oxidation.
PMID- 28420478
TI - [Research progress on metabolism of monocytes and macrophages in sepsis].
AB - OBJECTIVE: During sepsis, circulating leukocytes are in a hyper inflammatory
state, and with the progress of the inflammation, immune cells may become
tolerated. Glycolysis and pentose phosphate pathway are up-regulated but
oxidative phosphorylation is suppressed in hyper inflammatory cells, whereas
during immune tolerance, glycolysis is often down-regulated. In this review, we
will summarize the changes of cellular metabolic pathways in monocytes and
macrophages during sepsis. We also review how the metabolism of glucose, amino
acids, and fatty acids affect the function of monocytes and macrophages in
sepsis. Current literature indicated that metabolism plays a significant role in
regulating the functions of immune cells in sepsis, which might be a potential
therapy for sepsis and deserved further research.
PMID- 28420479
TI - Andrographolide disrupts meiotic maturation by blocking cytoskeletal
reorganisation and decreases the fertilisation potential of mouse oocytes.
AB - Andrographolide (AG) is a diterpenoid lactone isolated from the stem and leaves
of Andrographis paniculata Nees that is used for the effective treatment of
infectious diseases in Asian countries. Previous studies have reported adverse
effects of AG on female fertility in rodents; however, the underlying mechanisms
are unknown. The aim of the present study was to investigate the effects of AG on
the IVM of mouse oocytes and their fertilisation potential. Immature oocytes
incubated for 6, 14 or 24h in medium containing 5, 10 or 20MUM AG showed time-
and dose-dependent decreases in maturation rates compared with the control group.
Immunostaining revealed that AG exposure disrupted spindle organisation and
migration, as well as actin cap formation and cytokinesis. Furthermore, most
oocytes exposed to 20MUM AG underwent apoptosis, and the few oocytes exposed to 5
or 10MUM AG that reached MII exhibited lower fertilisation rates after
intracytoplasmic sperm injection. The findings of the present study suggest that
AG may disrupt mouse oocyte meiotic maturation by blocking cytoskeletal
reorganisation, and may thus have an adverse effect on female fertility.
PMID- 28420480
TI - Comparative analysis of granulosa cell gene expression in association with oocyte
competence in FSH-stimulated Holstein cows.
AB - Ovarian stimulation with exogenous FSH followed by FSH withdrawal or 'coasting'
is an effective means of increasing the number of oocytes obtainable for the in
vitro production of cattle embryos. However, the quality of the oocytes thus
obtained varies considerably from one cow to the next. The aim of the present
study was to gain a better understanding of the follicular conditions associated
with low oocyte developmental competence. Granulosa cells from 94 Holstein cows
in a commercial embryo production facility were collected following ovarian
stimulation and coasting. Microarray analysis showed 120 genes expressed with a
differential of at least 1.5 when comparing donors of mostly competent with
donors of mostly incompetent oocytes. Using ingenuity pathway analysis, we
revealed the main biological functions and potential upstream regulators that
distinguish donors of mostly incompetent oocytes. These are involved in cell
proliferation, apoptosis, lipid metabolism, retinol availability and insulin
signalling. In summary, we demonstrated that differences in follicle maturity at
collection could explain differences in oocyte competence associated with
individual animals. We also revealed deficiencies in lipid metabolism and retinol
signalling in granulosa cells from donors of mostly incompetent oocytes.
PMID- 28420481
TI - Safety and Feasibility of Subcutaneous Purse-String Suture of the Femoral Vein
After Electrophysiological Procedures on Uninterrupted Oral Anticoagulation.
AB - The aim of this study was to compare safety and feasibility of a subcutaneous
purse-string suture (PSS) with manual compression (MC) to gain hemostasis in
patients after multiple femoral venous punctures undergoing electrophysiological
procedures on uninterrupted oral anticoagulation (OAK). A total of 784 patients
who underwent catheter ablation for atrial fibrillation (n = 564) or (a)typical
atrial flutter (n = 220) were assessed. Four hundred sixty-two patients received
PSS (58.9%) and 322 patients (41.1%) received MC to gain hemostasis. All patients
were on uninterrupted full-dose OAK. During the procedure, weight-adapted heparin
was applied. Venous sheath diameter were 8Fr (n = 2)/11.5Fr (n = 1) for left
atrial or 8Fr (n = 1)/6Fr (n = 2) for right atrial procedures. No protamine was
administered at the end of the procedure. After PSS, patients' had 6 hours of bed
rest compared with 10 hours after MC (sheath removal after 4 hours followed by a
bandage for 6 hours). PSS was removed the following day. All patients underwent
duplex sonography of the access site the following day. Using the PSS, hemostasis
was achieved in 453 of 462 patients (98%). MC leads to hemostasis in all 322
patients. No difference was found between the 2 approaches regarding hematomas
(<5 cm or >5 cm), arterio-venous fistulas, or pseudoaneurysms. No major
complication such as ipsilateral leg ischemia, the need of vascular surgery, or
deep vein thrombosis occurred. In conclusion, PSS is a safe and effective way to
gain immediate hemostasis after multiple punctures of the femoral vein in
patients undergoing catheter ablation on OAK. PSS avoids MC and leads to shorter
patient immobilization.
PMID- 28420482
TI - Detection of driver drowsiness using wearable devices: A feasibility study of the
proximity sensor.
AB - BACKGROUND: Drowsiness is one of the major factors that cause crashes in the
transportation industry. Drowsiness detection systems can alert drowsy operators
and potentially reduce the risk of crashes. In this study, a Google-Glass-based
drowsiness detection system was developed and validated. METHODS: The proximity
sensor of Google Glass was used to monitor eye blink frequency. A simulated
driving study was carried out to validate the system. Driving performance and eye
blinks were compared between the two states of alertness and drowsiness while
driving. RESULTS: Drowsy drivers increased frequency of eye blinks, produced
longer braking response time and increased lane deviation, compared to when they
were alert. A threshold algorithm for proximity sensor can reliably detect eye
blinks and proved the feasibility of using Google Glass to detect operator
drowsiness. APPLICATIONS: This technology provides a new platform to detect
operator drowsiness and has the potential to reduce drowsiness-related crashes in
driving and aviation.
PMID- 28420483
TI - An evaluation of wearable sensors and their placements for analyzing construction
worker's trunk posture in laboratory conditions.
AB - This study investigates the effect of sensor placement on the analysis of trunk
posture for construction activities using two off-the-shelf systems. Experiments
were performed using a single-parameter monitoring wearable sensor (SPMWS), the
ActiGraph GT9X Link, which was worn at six locations on the body, and a multi
parameter monitoring wearable sensor (MPMWS), the Zephyr BioHarnessTM3, which was
worn at two body positions. One healthy male was recruited and conducted 10
experiment sessions to repeat measurements of trunk posture within our study.
Measurements of upper-body thoracic bending posture during the lifting and
lowering of raised deck materials in a laboratory setting were compared against
video-captured observations of posture. The measurements from the two sensors
were found to be in agreement during slow-motion symmetric bending activities
with a target bending of <=45 degrees . However, for asymmetric bending tasks,
when the SPMWS was placed on the chest, its readings were substantially different
from those of the MPMWS worn on the chest or under the armpit.
PMID- 28420484
TI - Prenatal diagnosis of Ectrodactyly-Ectodermal dysplasia-Cleft (EEC) syndrome in a
Chinese woman with a TP63 mutation.
PMID- 28420486
TI - Vitamins C and D.
PMID- 28420485
TI - Subcutaneous dermatofibrosarcoma protuberans, a rare subtype with predilection
for the head: A retrospective series of 18 cases.
AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis
and subcutaneous tissue. The subcutaneous variant is rare. OBJECTIVE: We sought
to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with
cutaneous DFSP (C-DFSP). METHODS: This work was a retrospective study of DFSP
treated in our institution. RESULTS: Of 124 cases of DFSP, 18 were SC-DFSP
(14.5%). Except for the deep location, the pathologic and genetic features were
indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases,
13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1
giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion
transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C
DFSP tumors (8.5%) were located on the head (P < .001). Of the 20 DFSP tumors on
the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC
DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP
tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP
(P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1
SC-DFSP, 1 C-DFSP). LIMITATIONS: Limitations include the retrospective aspect of
the study. CONCLUSIONS: Most DFSP tumors involving the head were subcutaneous and
required more complex surgery. Dermatologists should be aware of this atypical
presentation, especially in lesions involving the head.
PMID- 28420487
TI - Personal protective equipment solution for UK military medical personnel working
in an Ebola virus disease treatment unit in Sierra Leone.
AB - The combination of personal protective equipment (PPE) together with donning and
doffing protocols was designed to protect British and Canadian military medical
personnel in the Kerry Town Ebola Treatment Unit (ETU) in Sierra Leone. The PPE
solution was selected to protect medical staff from infectious risks, notably
Ebola virus, and chemical (hypochlorite) exposure. PPE maximized dexterity,
enabled personnel to work in hot temperatures for periods of up to 2h, protected
mucosal membranes when doffing outer layers, and minimized potential
contamination of the doffing area with infectious material by reducing the
requirement to spray PPE with hypochlorite. The ETU was equipped to allow medical
personnel to provide a higher level of care than witnessed in many existing ETUs.
This assured personnel working as part of the international response that they
would receive as close to Western treatment standards as possible if they were to
contract Ebola virus disease (EVD). PPE also enabled clinical interventions that
are not seen routinely in West African EVD treatment regimens, whilst providing a
robust protective barrier. Competency in using PPE was developed during a nine
day pre-deployment training programme. This allowed over 60 clinical personnel
per deployment to practice skills in PPE in a simulated ETU and in classrooms.
Overall, the training provided: (i) an evidence base underpinning the PPE
solution chosen; (ii) skills in donning and doffing of PPE; (iii) personnel
confidence in the selected PPE; and (iv) quantifiable testing of each
individual's capability to don PPE, perform tasks and doff PPE safely.
PMID- 28420488
TI - Mandibular step osteotomy using CAD/CAM-derived surgical splint: case report.
AB - Mandibular step osteotomy is a useful technique for large mandibular setbacks. We
report a case of a patient who had a mandibular step osteotomy using a CAD/CAM
derived wafer for mandibular setback with reduction of the arch.
PMID- 28420489
TI - Mast cells emerge as mediators of atherosclerosis: Special emphasis on IL-37
inhibition.
AB - In atherosclerosis lipoproteins stimulate the innate immune response, leading to
the release of inflammatory cytokines and chemokines. Hypercholesterolemia may
activate the synthesis and release of inflammatory cytokines such as IL-1, which
induces TNF release in mast cells (MCs). IL-1 and IL-1 family members orchestrate
a broadening list of inflammatory diseases, including atherosclerosis. MCs are
implicated in the pathophysiology of several diseases including allergy and
inflammation. Activated MCs, located perivascularly, contribute to inflammation
in atherosclerosis by producing inflammatory cytokines. MC IL-1-activation leads
to the immediate release of inflammatory chemical mediators and TNF, and late
inflammatory compounds such as cytokines. MCs can be activated by exogenous
cytokines, antigens, microbial products (LPS) and neurotransmitters and generate
IL-1 beta, TNF and several other inflammatory cytokines/chemokines along with
PGD2, leukotrienes, histamine and proteases. MCs activated with IL-1 induce
selective release of IL-6 without degranulation. TNF emerges as one of the most
potent inflammatory cytokines involved in the response due to LDL. Cytokines,
such as IL-1, IL-6, IL-33 and TNF, are generated in the inflammatory sites by
both macrophages and MCs, mediating atherosclerosis. IL-37 (IL-1 family member 7)
binds IL-18Ra chain and acts by an intracellular mechanism down-regulating the
expression of pro-inflammatory signals cJun, MAP kinase p38a, STAT transcription
factors and p53. Blocking IL-1 with IL-37 alleviates the symptoms in patients
with inflammatory diseases including arteriosclerosis. The impact of IL-37 on
inflammatory cytokines mediating atherosclerosis is beneficial and protective.
However, more studies are needed to better define this mechanism and the safety
and tolerability of IL-37.
PMID- 28420490
TI - Are herbarium mosses reliable indicators of historical nitrogen deposition?
AB - Mosses collected decades ago and stored in herbaria are often used to assess
historical nitrogen deposition. This method is effectively based on the
assumption that tissue N concentration remains constant during storage. The
present study raises serious doubt about the generality of that assumption. We
measured tissue N and C concentrations as well as delta15N, delta13C, Pb and Mg
in herbarium and present day samples of seven bryophyte species from six sites
across Denmark. While an increase in nitrogen deposition during the last century
is well-documented for the study site, we surprisingly found foliar N
concentration to be higher in historical samples than in modern samples. Based on
delta15N values and Pb concentration, we find nitrogen contamination of herbarium
specimens during storage to be the most likely cause, possibly in combination
with dilution though growth and/or decomposition during storage. We suggest ways
to assess contamination and recommend caution to be taken when using herbarium
specimens to assess historical pollution if exposure during storage cannot be
ruled out.
PMID- 28420491
TI - Telemedicine for patients with rheumatic diseases: Systematic review and proposal
for research agenda.
AB - OBJECTIVE: To systematically review the scientific literature regarding tele
rheumatology and draw conclusions about feasibility, effectiveness, and patient
satisfaction. METHODS: PubMed, Scopus, and Cochrane database searches were
performed (April 2016) using relevant MeSH and keyword terms for telemedicine and
rheumatic diseases. Articles were selected if reporting outcomes for feasibility,
effectiveness, and patient satisfaction and methodologically appraised using the
Cochrane Collaboration's tool for assessing risk of bias and a modified version
of CONSORT 2010 Statement. RESULTS: A total of 177 articles were screened, 23
were selected for the present review but only 9 were RCTs. Five studies reported
on feasibility, 14 effectiveness, and 9 satisfaction rates for different tele
rheumatology interventions grouped in synchronous (remotely delivered
consultation) and asynchronous (remote disease activity assessment; tele
monitoring of treatment strategies or rehabilitation; and remotely delivered self
management programs). Seven studies (30.4%) were on rheumatoid arthritis, 2
(8.7%) were on systemic sclerosis (1 including also rheumatoid arthritis
patients), 5 (21.7%) on fibromyalgia, 2 (8.7%) on osteoarthritis, 3 (13.0%) on
juvenile idiopathic arthritis and 4 (17.4%) on mixed disease cohorts.
Interventions and outcomes heterogeneity prevented meta-analysis of results.
Overall, feasibility and patient satisfaction rates were high or very high across
intervention types. Effectiveness was equal or higher than standard face-to-face
approach in controlled trials which, however, were affected by small sample size
and lack of blinding participants according to appraisal tools. CONCLUSION:
Telemedicine may provide a well-accepted way to remotely deliver consultation,
treatment and monitoring disease activity in rheumatology. Higher quality RCTs
demonstrating effectiveness of different tele-rheumatology interventions are
needed.
PMID- 28420492
TI - Commentary on: Research priorities for a multicenter child abuse pediatrics
network - CAPNET by Lindberg D et al., 2017: Need for internationally agreed
definitions of Child Maltreatment for research purposes.
PMID- 28420493
TI - Etiology of Human Genetic Disease on the Fly.
AB - The model organism Drosophila melanogaster has been at the forefront of genetic
studies since before the discovery of DNA. Although human disease modeling in
flies may still be rather novel, recent advances in genetic tool design and
genome sequencing now confer huge advantages in the fly system when modeling
human disease. In this review, we focus on new genomic tools for human gene
variant analysis; new uses for the Drosophila Genetic Reference Panel (DGRP) in
detection of background alleles that influence a phenotype; and several examples
of how multigenic conditions, both complex disorders and duplication and/or
deletion syndromes, can be effectively studied in the fly model system. Fruit
flies are a far cry from the quaint genetic model of the past, but rather,
continue to evolve as a powerful system for the study of human genetic disease.
PMID- 28420494
TI - Molecular regulation and role of angiogenesis in reproduction.
AB - Angiogenesis is an essential process for proper functioning of the female
reproductive system and for successful pregnancy realization. The multitude of
factors required for physiological angiogenesis and the complexity of regulation
of their temporal-spatial activities contribute to aberrations in human
fertilization and pregnancy outcomes. In this study, we reviewed the current
knowledge of the temporal expression patterns, functions, and regulatory
mechanisms of angiogenic factors during foliculogenesis, early
implantation/placentation and embryo development, as well as recurrent
spontaneous abortions. Angiogenic factors including vascular endothelial growth
factors and angiopoietins have documented roles in the development of primordial
follicles into mature antral follicles. They also participate in decidualization,
which is accompanied by the creation of an extensive network of vessels in the
stromal bed that support the growth of the embryo and the placenta, and maintain
early pregnancy. During placentation angiogenic and angiomodulatory cytokines, T
and B lymphocytes and macrophages affect angiogenesis in a context-dependent
manner. Defects in angiogenesis at the maternal-fetal interface contribute to
miscarriage in humans. The establishment of more polymorphisms in the genes
involved in angiogenesis/vasculogenesis, and their pathological phenotype and
expression could give opportunities for prediction, creating a therapeutic
strategy, and treatment of diseases related to female reproductive health and
problematic conception.
PMID- 28420495
TI - Fetal programming of the metabolic syndrome.
AB - Prenatal development is currently recognized as a critical period in the etiology
of human diseases. This is particularly so when an unfavorable environment
interacts with a genetic predisposition. The fetal programming concept suggests
that maternal nutritional imbalance and metabolic disturbances may have a
persistent and intergenerational effect on the health of offspring and on the
risk of diseases such as obesity, diabetes, and cardiovascular diseases.
PMID- 28420496
TI - The value of hysteroscopic management of cesarean scar pregnancy: a report of 44
cases.
AB - OBJECTIVE: With the incidence of cesarean scar pregnancy (CSP) rising, the
reports of serious adverse outcomes of it have increased gradually. The
management of CSP remains an inadequately explored clinical field, and there is
no consensus on it presently. The present study was performed to investigate the
efficacy and safety of operative hysteroscopy in the diagnosis and treatment of
CSP. MATERIALS AND METHODS: Forty-four patients with CSP underwent operative
hysteroscopy for removal of scar ectopic pregnancy in our institution. Among
them, hysteroscopy was combined with laparoscopy in two patients, three cases
with massive hemorrhage were pretreated with bilateral uterine artery
embolization before hysteroscopic surgery, and four patients were pretreated with
mifepristone (200 mg for 3 days) and methotrexate (25 mg for 2 days). Clinical
data, serum beta-human chorionic gonadotropin, myometrial thickness, residual
conceptus, cesarean scar defect, operation time, blood loss, and hospital stay
were recorded. RESULTS: All of the ectopic gestations were removed entirely by
operative hysteroscopy. Mean operation time was 34.8+/-16.5 minutes (range 20-120
minutes), and mean blood loss was 35.3+/-24.4 mL (range 5-100 mL). The mean
hospital stay was 5.0+/-3.01 days (range 1-19 days). Cesarean scar defect could
be diagnosed in 70% (31/44) of patients, while in 20/32 cases (63%), a conceptus
remained after uterine curettage only was performed. CONCLUSION: Operative
hysteroscopy might be recommended as a first-line treatment modality for patients
with a cesarean scar ectopic pregnancy, especially when myometrium thickness
between bladder and gestational sac is more than 3 mm.
PMID- 28420497
TI - Radical trachelectomy for early stage cervical cancer: A case series and
literature review.
AB - OBJECTIVE: Radical trachelectomy (RT) is an alternative treatment for preserving
fertility in patients with cervical cancer. Because women with operable cervical
cancer opting for fertility preservation are scarce, few cases have been reported
in Taiwan. Here we report our cases series. MATERIALS AND METHODS: We
retrospectively evaluated seven patients who underwent vaginal RT and three
patients who underwent abdominal RT in a single medical institute for a median
follow-up period of 5 years. RESULTS: The oncological outcome was highly
satisfactory. All patients survived and are currently disease-free, except for
two who had recurrence and received additional concurrent chemoradiation therapy.
Other complications included urinary tract infection, cervical stenosis, and
unilateral hydronephrosis. All complications were manageable with little long
term effects. However, no pregnancy was observed during the 5-year follow-up
period. CONCLUSION: RT is considered a complicated surgical procedure among
gynecological operations. Here we review the literature and describe several
factors associated with higher pregnancy rates.
PMID- 28420498
TI - Intraoperative aortic balloon occlusion in patients with placenta previa and/or
placenta accreta: a retrospective study.
AB - OBJECTIVE: To introduce the primary experience of using aortic balloon catheters
during cesarean section for placenta previa and/or placenta accreta. MATERIALS
AND METHODS: From January 2013 to May 2015, 43 patients who were preoperatively
diagnosed with major placenta previa and/or placenta accreta and who underwent
prophylactic aortic catheterization before caesarean section (CS) were included
in the study. We analyzed the clinical data of the study population. Surgery- and
catheterization-related complications were also reported. RESULTS: Major placenta
previa or placenta accreta was surgically confirmed in 42 patients, 28 of whom
had both conditions. The mean patient age was 32.3 +/- 5.5 years, whereas the
median gestational age at delivery was 260 (range, 153-280) days. Twenty-nine
(67.4%) patients had previously undergone CS, and 13 (30%) patients had undergone
emergency surgery for antenatal hemorrhage. The median estimated blood loss
during surgery was 500 (range, 100-3,000) mL, and the median duration of
occlusion was 20 (range, 5-32) minutes. Hysterectomy was performed in five
(11.6%) patients and uterine artery embolization in two (4.6%) patients. Two
patients with placenta percreta experienced surgery-related complications, and
two patients required hospital readmission. No major catheterization-related
complications were observed. Forty-two live births were recorded, and the Apgar
score of the infants at 5 minutes was > 7. CONCLUSION: Intraoperative aortic
balloon occlusion is a relatively safe method for treating placenta previa and/or
placenta accreta during scheduled and emergency CS and might be helpful to
prevent hysterectomy and embolization in women wishing to preserve fertility.
PMID- 28420499
TI - The associations between parity, other reproductive factors, and osteoarthritis
in women aged over 50 years; data from the Korean National Health and Nutrition
Examination Survey V (2010-2012).
AB - OBJECTIVE: To evaluate the relationships between sociodemographic factors,
reproductive history, and subsequent risk of osteoarthritis (OA) or pain of the
hip, knee, and back in Korean women. MATERIALS AND METHODS: This study included
data of 5101 women aged over 50 years, taken from the Korean National Health and
Nutritional Examination Survey V from 2010 to 2012. Women were stratified
according to parity, as well as delivery mode. Multivariate logistic regression
analysis was conducted to evaluate relationships between radiographic OA or
symptomatically possible OA (back, knee, or hip), and historical factors.
RESULTS: Vaginal delivery was associated with an increased risk of symptomatic
back OA [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.062, 2.881] but was
not associated with symptomatic knee and hip OA in adjusted analysis.
Radiographically, vaginal delivery was not associated with risks of back and knee
OA, but was negatively associated with hip OA (OR 0.184, 95% CI 0.039, 0.863),
compared to cesarean delivery. High parity (over 5) was associated with
radiographic knee OA (OR 1.328, 95% CI 1.006, 1.754) in adjusted analysis. High
parity (over 3) was associated with symptomatic back OA. CONCLUSION: Parity was
associated with higher risk of radiographic knee OA. Vaginal delivery was
positively associated with symptomatic back OA, but negatively associated with
radiographic knee OA. Further study is required to evaluate the mechanism between
delivery mode and subsequent OA.
PMID- 28420500
TI - Does different BMI influence oocyte and embryo quality by inducing fatty acid in
follicular fluid?
AB - OBJECTIVE: We aimed to assess the effects of obesity-related follicular fluid
(FF) fatty acids (FAs) on the number and quality of oocytes, good embryo quality
rate, and pregnancy rate. MATERIALS AND METHODS: This prospective cohort study
was conducted on 105 infertile women under the age of 38, who underwent
intracytoplasmic sperm injection (ICSI) from March 2015 to October 2015. They
were grouped into three body mass index (BMI) categories. The fatty acids
composition of the FF was analyzed by GC-MS head space method. We studied the FAs
correlation with BMI and ICSI outcomes. RESULTS: The distribution of fatty acids
did not differ significantly in each BMI group, with the exception for stearic
that was marginally significant (p=0.05). The mean number of mature oocytes did
not differ significantly between the BMI groups, the percent of Metaphase II
(MII) oocytes was inversely associated with the BMI (rs=-0.21, p=0.03). Kruskal
Wallis test showed that the distribution of good quality embryos' percentages
were different in at least two categories of studied BMI groups (p=0.009,
p=0.02). The mean concentration of palmitic acid was higher in nonpregnant
patients for all of the studied BMI classes (p=0.02, p=0.03, p=0.05), however,
stearic (p<0.001) and linolenic acids (p=0.01) were higher in nonpregnant normal
weight patients. CONCLUSION: Differences in BMI are not associated with the fatty
acid composition of the FF. The FF fatty acid possibly affects the outcome of
ICSI through the achievement of clinical pregnancy. Therefore, it is essential to
provide patients with nutritional counseling before they use assisted
reproductive techniques.
PMID- 28420501
TI - Bioinformatics analysis of gene expression profiles in B cells of postmenopausal
osteoporosis patients.
AB - OBJECTIVE: The aim of this study was to gain a better understanding of the
molecular mechanisms and identify more critical genes associated with the
pathogenesis of postmenopausal osteoporosis (PMOP). MATERIALS AND METHODS:
Microarray data of GSE13850 were download from the Gene Expression Omnibus
database. Differentially expressed genes (DEGs) were identified either in B cells
from postmenopausal female nonsmokers with high bone mineral density (BMD)
compared with those with low BMD (defined as DEG1 group) or in B cells from
postmenopausal female smokers with high BMD compared with postmenopausal female
nonsmokers with high BMD (defined as DEG2 group). Gene ontology and immune
related functional enrichment analysis of DEGs were performed. Additionally, the
protein-protein interaction network of all DEGs was constructed and subnetworks
of the hub genes were extracted. RESULTS: A total of 51 DEGs were identified in
the DEG1 group, including 30 up- and 21 downregulated genes. Besides, 86 DEGs
were identified in the DEG2 group, of which 46 were upregulated and 40 were
downregulated. Immune enrichment analysis showed DEGs were mainly enriched in
functions of CD molecules and chemokines and receptor, and the upregulated gene
interleukin 4 receptor (IL-4R) was significantly enriched. Moreover, guanine
nucleotide-binding protein G (GNAI2), filamin A alpha (FLNA), and transforming
growth factor-beta1 (TGFB1) were hub proteins in the protein-protein interaction
network. CONCLUSION: IL-4R, GNAI2, FLNA, and TGFB1 may be potential target genes
associated with the pathogenesis of PMOP. In particular, FLNA, and TGFB1 may be
affected by smoking, a risk factor of PMOP.
PMID- 28420502
TI - The impact of situation-background-assessment-recommendation (SBAR) on safety
attitudes in the obstetrics department.
AB - OBJECTIVE: Previous studies evaluating the situation-background-assessment
recommendation (SBAR) have been shown to increase effective nurse-physician
communication and collaboration. The purpose of this study is to evaluate the
impact of the SBAR technique on safety attitudes in the obstetrics department.
MATERIALS AND METHODS: This study implemented the SBAR Collaborative
Communication Education course and was conducted in a medical center from
February 2012 to March 2015, which included an educational session on fetal heart
rate monitoring, a case-based discussion, and a video demonstration on
traditional and SBAR communication. The nurses in the obstetrics department were
requested to report their clinical findings and recommendations using a novel
SBAR list when abnormal fetal heart beat tracings occurred. All obstetric nurses
were requested to complete the Chinese-version of the Safety Attitudes
Questionnaire before and after the SBAR educational course. The primary outcome
was to evaluate the effect of the SBAR technique on the safety attitudes of the
obstetrics department. The secondary outcome was to evaluate the effect of the
SBAR technique on the 5-minute Apgar score for neonates. RESULTS: Most values,
including teamwork climate, safety climate, job satisfaction, and working
conditions, significantly improved at both postintervention surveys compared with
the preintervention survey. There were no significant differences in the number
of the neonates with less than seven 5-minute Apgar scores between the pre- and
postintervention periods. CONCLUSION: The SBAR technique, which uses a novel
structured handover list, is a feasible tool for nurse-obstetrician
communication, and it may improve most dimensions of safety attitudes in the
obstetrics department.
PMID- 28420503
TI - Age is a major prognosticator in extremely low oocyte retrieval cycles.
AB - OBJECTIVE: Clinical prognosis appears to be varied in females with poor ovarian
response (POR), and poor responders defined by the Bologna criteria might not be
sufficiently homogeneous. The aim of this study was to determine the major
predictor of reproductive outcomes in extremely low oocyte retrieval cycles.
MATERIALS AND METHODS: A cohort of fresh in vitro fertilization/intracytoplasmic
sperm injection cycles (n = 858) was analyzed from January 2001 to September
2014. Females from whom zero, one, two, or three oocytes were retrieved following
ovarian stimulation were examined. Univariate analyses were performed to
determine the association of pregnancy rate with potential confounding variables.
Multiple logistic regression analysis was subsequently performed to identify
factors that affected the occurrence of pregnancy. RESULTS: The clinical
pregnancy rate was higher in women aged < 40 years, long protocol, and high
embryo score in univariate analysis. After adjusting for confounding factors in
multivariate analysis, the maternal age [odds ratio (OR) = 0.91], primary or
secondary infertility (OR = 1.99), number of matured oocytes retrieved (OR =
0.64), and score of embryos transferred (OR = 1.39) were significantly associated
with the clinical pregnancy rate per cycle and per transfer. In the age subgroup
analysis, POR females aged < 35 years significantly demonstrated the highest
number of matured oocytes, embryo scores, and clinical pregnancy rates compared
with POR females aged 35-40 years and >= 40 years. CONCLUSION: This study
highlights the predictive value of maternal age and embryo quality on the
probability of pregnancy in females with extremely low oocyte retrieval cycles.
Young females with few eggs collected can still achieve acceptable pregnancy
probability as long as they have good-quality embryos. Future randomized control
trials for POR using the Bologna criteria should first stratify patients into
different age groups.
PMID- 28420504
TI - The clinical profile of young and adolescent women with laparoscopically
diagnosed endometriosis in a Singapore tertiary hospital.
AB - OBJECTIVE: Endometriosis has been increasingly recognized as the cause of severe
dysmenorrhea among younger women including adolescents, often with significant
delay from time of presentation to diagnosis. Data on the South East Asian women
is scarce. This study aims to describe the disease pattern in a group of young
Asian women with histological diagnosis of endometriosis in our center. MATERIALS
AND METHODS: A total of 709 laparoscopic operations were performed for
endometriosis in our center between 2000 and 2007. Women aged 25 years old and
below were included in this study. Details regarding clinical presentation and
severity of disease were retrospectively reviewed and described. RESULTS: A total
of 45 women were included in this study, aged between 14 years and 25 years.
Thirty seven patients (82.3%) were aged between 21 years and 25 years. Racial
distribution was as follows: 57.8% Chinese, 26.7% Malay, and 15.6% Indian.
Dysmenorrhea was the commonest symptom (84.4%); 44.4% of which were described as
mild. Eleven patients (24.4%) presented with severe symptoms resulting in absence
from school or work. Severity of endometriosis during laparoscopy was staged
using the rAFS staging system, and was 11.1%, 17.8%, 28.9%, and 42.2% for disease
Stage I, Stage II, Stage III, and Stage IV, respectively. CONCLUSION:
Endometriosis can cause severe disease even in adolescents and young females.
Increased awareness among patients and healthcare providers would raise a higher
index of suspicion for endometriosis in these women, with consequent early
treatment which may result in better functional and fertility outcomes.
PMID- 28420505
TI - Risk factors and management of vaginal mesh erosion after pelvic organ prolapse
surgery.
AB - OBJECTIVE: Mesh erosion is a serious and not uncommon complication in women
undergoing vaginal mesh repair. We hypothesized that mesh erosion is associated
with the patient's comorbidities, surgical procedures, and mesh material. The
aims of this study were to identify the risk factors and optimal management for
mesh erosion. MATERIALS AND METHODS: All women who underwent vaginal mesh repair
from 2004 to 2014 were retrospectively reviewed. Data on patients'
characteristics, presenting symptoms, treatment and outcomes were collected from
their medical records. RESULTS: A total of 741 women underwent vaginal mesh
repairs, of whom 47 had mesh erosion. The median follow-up period was 13 months
(range 3-84 months). Another nine patients with mesh erosion were referred form
other hospitals. Multivariate analysis revealed that concomitant hysterectomy
(odds ratio 27.02, 95% confidence interval 12.35-58.82; p < 0.01) and
hypertension (odds ratio 5.95, 95% confidence interval 2.43-14.49; p < 0.01) were
independent risk factors for mesh erosion. Of these 56 women, 20 (36%) were
successfully treated by conservative management, while 36 (64%) required
subsequent surgical revision. Compared with surgery, conservative treatment was
successful if the size of the erosion was smaller than 0.5 cm (p < 0.01). Six
patients (17%) had recurrent erosions after primary revision, but all
successfully healed after the second surgery. CONCLUSION: Concomitant
hysterectomy and hypertension were associated with mesh erosion. In the
management of mesh erosion, conservative treatment can be tried as the first-line
treatment for smaller erosions, while surgical repair for larger erosions.
Recurrent erosions could happen and requires repairs several times.
PMID- 28420506
TI - Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using
cervical length and granulocyte elastase.
AB - OBJECTIVE: The purpose of this study was to evaluate sonographic cervical length
(CL) and granulocyte elastase (GE) in cervical secretion as predictors of preterm
delivery in asymptomatic twin pregnancies. MATERIALS AND METHODS: This study
prospectively enrolled asymptomatic twin pregnancies with CL < 25 mm at 22-29
weeks of gestation. All women were hospitalized for preterm labor, and the
cervical secretion was obtained for GE testing on admission. The results of CL
measurement and GE testing were reviewed, and the relationship between each
variables and preterm delivery prior to 34 weeks of gestation was assessed.
RESULTS: Overall, we included 54 women with twin pregnancies, of which 12 (22.2%)
had preterm deliveries prior to 34 weeks of gestation. A CL of <20 mm was
significantly associated with preterm delivery with an odds ratio of 4.88 (95%
confidence limit, 1.15-20.73). GE was not an independent predictive marker for
preterm delivery. We also performed a subgroup analysis on the combination of CL
and GE for predicting preterm delivery. Among the patients with GE(-), CL < 20 mm
markedly increased the risk of preterm delivery with an odds ratio of 10.89 (95%
confidence limit, 1.40-77.10). CL was not associated with preterm delivery among
those with GE(+). Those with negative GE and shorter CL demonstrated the shortest
duration of pregnancy after admission. CONCLUSION: The combination of sonographic
CL and GE of cervical secretion is useful to predict the risk of preterm delivery
in asymptomatic twin pregnancies.
PMID- 28420507
TI - Asymptomatic pyuria in pregnant women during the first trimester is associated
with an increased risk of adverse obstetrical outcomes.
AB - OBJECTIVE: Urinalysis is included in the prenatal examination in the first
trimester in Taiwan, in contrast to Western countries. We aimed to investigate
whether asymptomatic pyuria as detected by urinalysis was associated with adverse
perinatal outcomes. MATERIALS AND METHODS: A total of 1187 singleton pregnant
women who received prenatal care at Kaohsiung Chang Gung Memorial Hospital
between January 2012 and December 2013 were included for retrospective analysis.
We defined asymptomatic pyuria as the presence of 15 or more white blood
cells/MUL in midstream urine without symptoms. Adverse perinatal outcomes
including preterm delivery, preterm premature rupture of membrane, low birth
weight, and Apgar scores were analyzed. Univariate and multivariate logistic
regression analyses were used to identify independent predictors. RESULTS: The
prevalence of asymptomatic pyuria was 21.3% in our cohort. Univariate analysis
showed that pyuria was the only factor associated with preterm delivery before 36
weeks of pregnancy, preterm premature rupture of membrane, and low birth weight.
In multivariate analysis, both pyuria (odds ratio: 4.89, 95% confidence interval:
1.80-13.25, p=0.002) and a maternal age of 35 years or older (odds ratio: 3.46,
95% confidence interval: 1.11-10.78, p=0.033) were significant independent
predictors for a low 5 minute Apgar score (<7). CONCLUSION: The identification of
asymptomatic pyuria via urinalysis in the first trimester may be a predictor for
adverse perinatal outcomes.
PMID- 28420508
TI - A promising protein responsible for overactive bladder in ovariectomized mice.
AB - OBJECTIVE: Ovariectomy (OVX) in mice is a model mimicking a neuro-electronic
proof of an overactive bladder in postmenopausal women. Overactive bladder (OAB)
was recently found to be due to an altered gap junction protein in a rat model.
Thus, this study was conducted to evaluate changes in cell junction protein
expression and composition in the bladder of OVX mice. MATERIALS AND METHODS:
Thirty-six virgin female mice were randomized into three groups: mice with a sham
operation only (control), OVX mice without estradiol (E2) replacement, and OVX
mice with E2 replacement (OVX + E2). Cystometry assessment was conducted and cell
junction-associated protein zonula occludens-2 (ZO-2) expression was measured
after 8 weeks. Voiding interval values (time between voids) were assessed in mice
under anesthesia. After measurements, the bladders were removed for proteomic
analysis using the label-free quantitative proteomics and liquid chromatography
mass spectrometry technology. Lastly, immunohistochemistry (IHC) and Western blot
were used to confirm the location and level, respectively, of ZO-2 expression.
RESULTS: We identified 73 differentially expressed proteins in the bladder of OVX
mice. The OVX mice showed significantly lower voiding interval values. Voiding
interval values were significantly higher in the OVX + E2 group than in the OVX
group. Urothelial thicknesses in the bladder were also significantly lower in the
OVX group than in the control group. E2 replacement reversed the urothelium
layers. Additionally, the expression of ZO-2, a tight junction protein, was the
most affected by OVX treatment. IHC and Western blot confirmed the downregulation
of ZO-2 in the bladder of OVX mice. Expression of ZO-2 protein was significantly
increased in OVX + E2 group compared with OVX group. CONCLUSION: This exploratory
study estimated changes in protein expression and composition in the bladder of
OVX mice. These changes may be associated with the molecular mechanisms of OAB.
PMID- 28420509
TI - Effect of a gymnastics program on sleep characteristics in pregnant women.
AB - OBJECTIVE: The quality and quantity of sleep represent important health issues in
pregnant women. Sleep disturbances could be associated, beyond alteration of
quality of life, with poor pregnancy outcome. Our aim was to investigate the
effect of a regular, specific, medium-term physical training program on sleep
characteristics in healthy pregnant women. MATERIALS AND METHODS: A total of 132
healthy pregnant women, with gestational age between 18 weeks and 22 weeks, were
enrolled in a prospective study. They were allocated into two groups; the first
group involved 79 women (average age, 29.4 years) who performed a specific
gymnastics program of 10 weeks, and the second group involved 53 pregnant women
(average age, 27.9 years) who did not perform gymnastics. All participants
completed a comprehensive questionnaire at baseline and after 10 weeks concerning
general data, sleep characteristics, and psycho-emotional status. The changes
arising within a diverse set of characteristics were followed and compared for
the two groups using parametric and nonparametric statistics. RESULTS: In the
control group, we observed significant worsening of 12 out of the 14 studied
parameters during the 10-week period. In comparison with the women who did not
perform gymnastics, women who performed specific gymnastics showed the following
characteristics: (1) significantly less deterioration of psycho-emotional status
(stress and anxiety levels); (2) the same general pattern of decrease in sleep
quality, which is related to the progression of pregnancy; and (3) a significant
attenuation of the worsening of several sleep characteristics, such as restless
sleep, snoring, diurnal tiredness, and excessive daytime sleepiness. Nocturnal
and diurnal sleep quantity increased significantly in both groups. CONCLUSION:
The 10-week training program designed for pregnant women has an overall
beneficial effect on sleep characteristics, not by improving them but by
attenuating their general deterioration related to the progression of pregnancy.
Our data strengthen the general recommendation regarding participation of
pregnant women in specific exercise programs, mainly for maintaining their psycho
emotional and general well-being.
PMID- 28420510
TI - Gene set-based analysis of mucinous ovarian carcinoma.
AB - OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon subtype of epithelial
ovarian cancers, and the pathogenesis is still poorly understood because of its
rarity. We conducted a gene set-based analysis to investigate the pathogenesis of
MOC by integrating microarray gene expression datasets based on the regularity of
functions defined by gene ontology or canonical pathway databases. MATERIALS AND
METHODS: Forty-five pairs of MOC and normal ovarian tissue sample gene expression
profiles were downloaded from the National Center for Biotechnology Information
Gene Expression Omnibus database. The gene expression profiles were converted to
the gene set regularity indexes by measuring the change of gene expression
ordering in a gene set. Then the pathogenesis of MOC was investigated with the
differences of function regularity with the gene set regularity indexes between
the MOC and normal control samples. RESULTS: The informativeness of the gene set
regularity indexes was sufficient for machine learning to accurately recognize
and classify the functional regulation patterns with an accuracy of 99.44%. The
statistical analysis revealed that the GTPase regulators and receptor tyrosine
kinase erbB-2 (ERBB2) were the most important aberrations; the exploratory factor
analysis revealed phosphoinositide 3-kinase-activating kinase, G-protein coupled
receptor pathway, oxidoreductase activity, immune response, peptidase activity,
regulation of translation, and transport and channel activity were also involved
in the pathogenesis of MOC. CONCLUSION: Investigating the pathogenesis of MOC
with the functionome provided a comprehensive view of the deregulated functions
of this disease. In addition to GTPase regulators and ERBB2, a plenty of
deregulated functions such as phosphoinositide 3-kinase, G-protein coupled
receptor pathway, and immune response also participated in the interaction
network of MOC pathogenesis.
PMID- 28420511
TI - Prenatal diagnosis and molecular cytogenetic characterization of concomitant
familial small supernumerary marker chromosome derived from chromosome 4q (4q11.1
q13.2) and 5q13.2 microdeletion with no apparent phenotypic abnormality.
AB - OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic
characterization of concomitant familial small supernumerary marker chromosome 4
[sSMC(4)] derived from 4q11.1-q12 and q13.2, and 5q13.2 microdeletion with no
apparent phenotypic abnormality. MATERIALS AND METHODS: A 32-year-old woman
underwent amniocentesis at 21 weeks of gestation because of absent nasal bone on
fetal ultrasound. Amniocentesis revealed a karyotype of 47,XX,+mar[13]/46,XX[3].
Array comparative genomic hybridization analysis on the cultured amniocytes
revealed a 2.752-Mb duplication at 4q11-q12, a 1.949-Mb duplication at 4q13.2,
and a 1.65-Mb deletion at 5q13.2. The woman underwent repeat amniocentesis at 24
weeks of gestation for molecular cytogenetic characterization. The phenotypically
normal parents and their elder son underwent genetic analysis. RESULTS: At repeat
amniocentesis, interphase fluorescence in situ hybridization analysis on
uncultured amniocytes revealed 79.25% (84/106) mosaicism for the sSMC(4), and
metaphase fluorescence in situ hybridization analysis on cultured amniocytes
revealed that all 20 cells examined (100%) had the sSMC(4). Polymorphic DNA
marker analysis on uncultured amniocytes excluded uniparental disomy 4. The
father had a karyotype of 47,XY,+mar[2]/46,XY[38], and interphase fluorescence in
situ hybridization revealed 2.91% (3/103) mosaicism for the sSMC(4) in his
peripheral blood. The mother carried the 5q13.2 microdeletion. The elder son had
a karyotype of 47,XY,+mar[27]/ 46,XY[13] with duplications of 4q11-q12 and
4q13.2. A 3105 g female baby was delivered at term with no apparent phenotypic
abnormality. CONCLUSION: Prenatal diagnosis of concomitant sSMC and microdeletion
should raise a suspicion of familial inheritance.
PMID- 28420512
TI - Managing vulvovaginal hematoma by arterial embolization as first-line hemostatic
therapy.
AB - OBJECTIVE: A puerperal vulvovaginal hematoma may continue to grow after a
surgical procedure and may require blood transfusion. Thus, we selected arterial
embolization for hemostasis as the first-line management in two cases of large
vulvovaginal hematoma. MATERIALS AND METHODS: Case 1 was a 32-year-old pregnant
woman. After delivery, a 10-cm vulvar hematoma developed. An enhanced computed
tomography (CT) scan revealed active bleeding. Arterial embolization was
performed and complete hemostasis was obtained. Case 2 was a 34-year-old woman
with a recurring hematoma after delivery. An enhanced CT scan revealed
extravasation in the hematoma. Gelatin sponges were applied and complete
hemostasis was obtained. In both cases, arterial embolization was successful
without requiring blood transfusions. RESULTS AND CONCLUSION: We successfully
managed two cases of puerperal vulvovaginal hematoma by arterial embolization
based on the evaluation of an enhanced CT scan. In conclusion, we suggest
arterial embolization to be a viable option for first-line treatment in the
management of vulvovaginal hematomas.
PMID- 28420513
TI - Euchromatic variants of 8q21.2 in twins.
AB - OBJECTIVE: Euchromatic variants (EVs) of 8q21.2 are extremely rare chromosomal
abnormalities. So, far there have only been two reports on EVs of 8q21.2. Here,
we report an 8q21.2 EV detected in cultured amniotic-fluid cells of twins. It was
later found to be inherited from the mother, who did not present with abnormal
phenotypes. CASE REPORT: A pregnant woman underwent amniocentesis at 16 weeks of
gestation because of advanced maternal age. This pregnancy was monozygotic twins
conceived naturally. A cytogenetic analysis of cultured amniocytes revealed
46,XY,?dup(8)(q21.2). Chromosomal microarray revealed no abnormalities. C-banding
and fluorescent in situ hybridization using chromosome 8 painting probe suggested
euchromatic nature of the extra chromosomal band. Karyotyping of the parents
showed that the EV was inherited from the mother. CONCLUSION: Many, but not all,
EVs are clinically innocuous. This is the first case of 8q21.2 EV reported in the
ethnic Han. More cases are needed to clarify whether 8q21.2 duplication as a bona
fide EV.
PMID- 28420514
TI - Detection of mosaic 15q11.1-q11.2 deletion encompassing NBEAP1 and POTEB in a
fetus with diffuse lymphangiomatosis.
AB - OBJECTIVE: We present cytogenetic and molecular cytogenetic diagnoses of mosaic
deletion of chromosome 15q11.1-q11.2 in a fetus with diffuse lymphangiomatosis.
CASE REPORT: A 33-year-old woman underwent amniocentesis at 22 weeks of gestation
because of fetal diffuse lymphangiomatosis involving left-side chest, abdominal
cavity, thigh and vulva, and intrauterine growth restriction. Amniocentesis
revealed a karyotype of 46,XX,del(15) (q11.1q11.2)[9]/46,XX[26]. The mother had a
karyotype of 46,XX. The father had a karyotype of 46,XY. The parents elected to
terminate the pregnancy. A 610-g female fetus was delivered at 23 weeks of
gestation with large cystic lymphangioma over the left abdomen, thigh, and vulva.
The umbilical cord had a karyotype of 46,XX,del(15)(q11.1q11.2)[24]/ 46,XX[16].
The placental tissue had a karyotype of 46,XX,del(15)(q11.1q11.2)[23]/ 46,XX[17].
Array comparative genomic hybridization analysis of the umbilical cord and
placenta revealed a 2.42-Mb deletion of 15q11.1-q11.2 encompassing the genes of
NBEAP1 and POTEB. CONCLUSION: Deletion of 15q11.1-q11.2 encompassing NBEAP1 and
POTEB may be associated with diffuse lymphangiomatosis.
PMID- 28420515
TI - Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a
small supernumerary marker chromosome derived from chromosome 2.
AB - OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic
characterization of mosaicism for a small supernumerary marker chromosome (sSMC)
derived from chromosome 2. CASE REPORT: A 42-year-old woman underwent
amniocentesis at 17 weeks of gestation because of advanced maternal age.
Amniocentesis revealed a karyotype of 47,XY,+mar[10]/46,XY[12]. The parental
karyotypes were normal. Array comparative genomic hybridization analysis of the
DNA extracted from cultured amniocytes revealed no genomic imbalance. Spectral
karyotyping analysis failed to identify the sSMC. Metaphase fluorescence in situ
hybridization analysis using the satellite probes CEP1/5/19, CEP2, CEP3, CEP4,
CEP6, CEP7, CEP8, CEP9, CEP10, CEP12, CEP13/21, CEP14/22, CEP15, CEP16, and CEP20
revealed a result of 47,XY,+mar .ish der(2)(D2Z+)[10]. The sSMC was derived from
the alpha satellite of chromosome 2. Polymorphic DNA marker analysis using the
markers specific for chromosome 2 on the DNAs extracted from cultured amniocytes
and parental bloods excluded uniparental disomy 2. At 39 weeks of gestation, a
healthy 3394-g male baby was delivered with no phenotypic abnormality. The cord
blood had a karyotype of 47,XY,+mar[21]/46,XY[19]. CONCLUSION: Array comparative
genomic hybridization and spectral karyotyping may fail to detect an sSMC derived
from alpha satellite, which needs satellite probes for confirmation.
PMID- 28420516
TI - Prenatal diagnosis and molecular cytogenetic characterization of low-level mosaic
trisomy 12 at amniocentesis associated with a favorable pregnancy outcome.
AB - OBJECTIVE: We present prenatal diagnosis of low-level mosaic trisomy 12. CASE
REPORT: A 40-year-old woman underwent amniocentesis at 18 weeks of gestation
because of advanced maternal age, which revealed a karyotype of
47,XX,+12[5]/46,XX[24] consistent with 17.2% (5/29) mosaicism for trisomy 12.
Repeat amniocentesis performed at 21 weeks of gestation revealed a karyotype of
47,XX,+12[4]/46,XX[6] consistent with 40% (4/10) mosaicism for trisomy 12.
Interphase fluorescence in situ hybridization (FISH) on 112 uncultured amniocytes
detected 23 cells with trisomy 12 consistent with 20.5% (23/112) mosaicism for
trisomy 12. Polymorphic DNA marker analysis excluded uniparental disomy 12. Array
comparative genomic hybridization (aCGH) on uncultured amniocytes revealed a
result of arr 12p13.33q24.33 (230,451-133,773,499) * 2.2, 17p12 (14,191,925
15,442,037) * 1.0 consistent with 10-20% mosaic trisomy 12. The father carried
the 17p12 microdeletion. The fetal ultrasound findings were unremarkable. A 3958
g female fetus was delivered at 37 weeks of gestation with no phenotypic
abnormality. The cord blood had a karyotype of 46,XX. Postnatal interphase FISH
on urinary cells revealed 7.14% (7/98) mosaicism for trisomy 12. CONCLUSION: Low
level mosaic trisomy 12 at amniocentesis can be associated with a favorable
pregnancy outcome. Interphase FISH and aCGH on uncultured amniocytes are useful
for confirmation of low-level mosaic trisomy 12 at amniocentesis.
PMID- 28420517
TI - Ileocecal endometriosis: diagnosis and management.
AB - OBJECTIVE: Ileocecal endometriosis is rare. Symptoms range from no symptoms,
cramps, vomiting, to acute intestinal obstruction. Our objective was to review
our cases, clarify, and resume its most appropriate management focusing on the
factors to determine diagnosis. This is a retrospective study by revision of
medical charts of all ileal endometriosis cases of our unit from 2006 to 2014.
CASE REPORT: Seven cases were found; three (43%) had previous endometriosis
laparoscopic diagnosis, four (57%) had partial bowel obstruction episodes, three
(43%) had chronic pelvic pain, and one developed acute intestinal obstruction in
postoperative ileostomy closure. In three (43%), the diagnosis was made with
magnetic resonance imaging (MRI) and double contrast barium enema, in one (14%)
only with MRI, and the other three (43%) during surgery. All patients underwent
resection of the ileum and evolved favorably. CONCLUSION: Variability in symptoms
hinders diagnosis. The gold standard for diagnosis is MRI, but clinical suspicion
optimizes imaging test diagnosis. Segmental resection should be indicated in the
majority of the cases.
PMID- 28420518
TI - Acute small bowel obstruction caused by barbed suture on the second day after
laparoscopic hysterosacropexy: A case report and literature review.
AB - OBJECTIVE: To report a case of small bowel obstruction caused by barbed suture
applied in hysterosacropexy, and possible solutions. CASE REPORT: A 57-year-old
woman underwent laparoscopic hysterosacropexy for a Stage 2 uterine prolapse,
presenting with acute abdominal pain and a bowel obstruction syndrome 2 days
following the surgery. Conservative treatment was given, but the symptoms did not
improve and gradually became worse. Diagnostic laparoscopy was performed on the
7th day after the hysterosacropexy, and the volvulus was found. The residual end
of the barbed V-Loc adopted in the peritoneal closure was incidentally hooked to
the mesentery and caused small bowel obstruction. The redundant V-Loc was
released and cut off at 2 cm. Neither bowel ischemia nor significant bowel injury
was noted. Two days later, she was discharged without complication. CONCLUSION: A
barbed suture has a risk of bowel obstruction when used in surgery. To avoid a
grave prognosis, early diagnosis and prompt management of complication is
necessary.
PMID- 28420519
TI - Simultaneous cul-de-sac and tubal pregnancy following in vitro fertilization.
AB - OBJECTIVE: The aim of this study is to share a valuable experience of heterotopic
pregnancy following in vitro fertilization. CASE REPORT: A 37-year-old, gravida
3, para 2 (cesarean section 2 times), woman underwent in vitro fertilization with
three embryos transferred. On Day 23 after the embryo transfer, right tubal
pregnancy with a 0.7-cm gestational sac was found by ultrasound, and her serum
beta-human chorionic gonadotropin level was 81,388 mIU/mL. She underwent a
laparotomy with right salpingectomy. On Day 43 after the embryo transfer,
intermittent abdominal pains developed. A live fetus with a crown-rump length of
2.0 cm was found in the cul-de-sac. Under the diagnosis of abdominal pregnancy,
she was admitted for sona-guided KCl and methotrexate injections. She received
four units of packed red blood cells due to a drop in hemoglobin level from 12.5
g/dL to 8.6 g/dL. The patient recovered well, and the serum beta-human chorionic
gonadotropin declined to <10 mIU/mL. CONCLUSION: Various forms of ectopic
pregnancy should be kept in mind in early pregnancy following in vitro
fertilization.
PMID- 28420520
TI - The association of enchondromatosis with malignant transformed chondrosarcoma and
ovarian juvenile granulosa cell tumor (Ollier disease).
AB - OBJECTIVE: Ovarian juvenile granulosa cell tumor has an interesting association
with multiple enchondromatosis (Ollier disease and Maffucci syndrome) and should
be considered a leading diagnosis when an ovarian mass is found in young patients
with these conditions. Besides the association with nonskeletal malignancies,
there is a high risk of malignant transformation of enchondroma in chondrosarcoma
as was also the case in this instance. CASE REPORT: The report uses multiple
images to document the representative and characteristic markers of multiple
enchondromas in a 22-year-old patient with Ollier disease complicated by
malignant transformation of chondrosarcoma and in whom the disease is associated
with ovarian juvenile granulosa cell tumor of the right ovary. CONCLUSION: It is
important to recognize that when the female patient presents with
enchondromatosis and a large unilateral multilocular-solid ovarian mass, the
specific diagnosis of granulosa cell tumor can be made with high accuracy.
PMID- 28420521
TI - Delayed postcoital vaginal cuff dehiscence with small bowel evisceration after
robotic-assisted staging surgery.
AB - OBJECTIVE: We report a rare case of vaginal cuff dehiscence with small bowel
evisceration at 7 months post robotic-staging surgery. CASE REPORT: A 41-year-old
woman was sent to the emergency room with sudden onset of abdominal pain, vaginal
bleeding, and vaginal protruding mass after sexual activity. She had a history of
synchronous uterine and ovarian cancer treated with robotic-staging surgery 7
months before. Then she received six courses of postoperative adjuvant
chemotherapy, and the last chemotherapy ended 1 month ago. At the operation room,
some small bowel loops were noted in the vaginal tip with cuff dehiscence and
bleeding. After repositioning of the small bowel, a 2.5-cm vaginal cuff
dehiscence was repaired transvaginally. The patient recovered well, and is free
of disease and has normal sexual activity 2 months after repairs. CONCLUSION:
Unusual delayed-type vaginal cuff dehiscence hints the possibility that a
combination of robotic surgery and postoperative chemotherapy might result in
delayed healing of the vaginal cuff.
PMID- 28420522
TI - Successful treatment of gestational trophoblastic neoplasia in the uterine cornus
with laparoscopic cornuostomy and postoperative methotrexate injection.
AB - OBJECTIVE: Management of cornual gestational trophoblastic neoplasia (GTN) has
never been reported. Here, we describe the first case of cornual GTN. CASE
REPORT: A 32-year-old woman was diagnosed with left cornual GTN after evacuation
of a complete mole. Laparoscopic cornuostomy was performed with intramural
vasopression injection and barbed sutures. Histopathology revealed hydropic
chorionic villi. Complete hydatidiform mole was diagnosed, and treated with
adjuvant methotrexate, to address the poor decline of beta-human chorionic
gonadotropin levels during follow-up. The beta- human chorionic gonadotropin
levels declined to < 1 mIU/mL 9 months after cornuostomy. She successfully
conceived 16 months after cornuostomy, and underwent cesarean section at 37
gestational weeks due to concomitant severe preeclampsia. CONCLUSION: Cornual GTN
can be successfully managed with laparoscopic cornuostomy and adjuvant
methotrexate.
PMID- 28420523
TI - Molecular cytogenetic characterization and prenatal diagnosis of familial Xp22.33
microdeletion encompassing short stature homeobox gene in a male fetus with a
favorable outcome.
PMID- 28420524
TI - Prenatal diagnosis of mosaicism for trisomy 15 in a single colony at
amniocentesis with a favorable fetal outcome.
PMID- 28420525
TI - Sclerotherapy for placenta accreta: Some concerns.
PMID- 28420526
TI - Response to the comments of Dr Shigeki Matsubara.
PMID- 28420527
TI - Corrigendum to "First trimester combined test for Down syndrome screening in
unselected pregnancies - A report of a 13-year experience" [Taiwan J Obstet
Gynecol 52 (4) (2013) 523-526].
PMID- 28420528
TI - Two-dimensional gas chromatography with electron capture detection for the
analysis of atmospheric ozone depleting halocarbons.
AB - This study is to develop a GC*GC method with electron capture detection (ECD) to
analyze atmospheric halocarbons in the concentration range of parts per trillion
by volume (pptv). To enrich atmospheric halocarbons a home-built thermal
desorption (TD) device was coupled to the GC*GC-ECD. The technique of flow
modulation was adopted using a Deans switch for GC*GC. Several column
combinations of first and second dimensions were tested and the column set of DB
5*TG-1301 was found to show the best orthogonality for halocarbons. A series of
modulation parameters were tested for their optimal settings. The modulation
period (PM) was found to have minimal wrap-around when set at 3s. The modulation
ratio (MR) was determined to be 7.82 to ensure reproducible results and maximum
sensitivity. The modulation duty cycle (DC) was calculated to be approximately
0.17. Nine halocarbons were separated successfully and seven were calibrated with
the use of a certified standard gas mixture. The correlation coefficients (R2)
were greater than 0.9972. The reproducibility was better than 1.90% as expressed
in relative standard deviation (RSD; N=30) and the detection limits were in the
range of pptv for the target halocarbons. A field test by continuous analyzing
ambient air with hourly resolution was performed to show the stability of the
method as suggested by the homogeneity of certain halocarbons, while also
reflecting concentration variation for others when emissions did arise.
PMID- 28420529
TI - Separation of antibody monomer-dimer mixtures by frontal analysis.
AB - The removal of aggregates, particularly soluble dimers, from monoclonal
antibodies (mAbs) remains a persistent challenge in downstream processing. In
this work, we have examined the separation of an antibody monomer from its dimer
on the cation exchange resin Nuvia HR-S (Bio-Rad Laboratories) using frontal
analysis. In this process, a mixture of monomer and dimer is continuously fed to
the column under conditions where the mixture is favorably bound, resulting in
two breakthrough fronts whose monomer and dimer compositions are determined by
the multi-component equilibrium and kinetics of the system. Experimentally, the
selectivity for dimer was found to vary substantially with ionic strength, being
lowest when conditions favor the strongest binding, and increasing to a maximum
at intermediate ionic strengths where rapid exchange with the bound monomer can
occur. A mechanistic model is developed to describe the competitive binding
frontal analysis process, assuming pore diffusion and a significant kinetic
resistance to binding as a function of ionic strength. The model was solved
numerically and was able to describe both the frontal analysis processes and
batch adsorption experimental data, accounting for process parameters such as
feed composition and salt concentration. The resulting model can be used to
optimize column operating conditions for yield and purity.
PMID- 28420530
TI - Rapid determination of the various native forms of vitamin B6 and B2 in cow's
milk using ultra-high performance liquid chromatography.
AB - As the formation of pyridoxal phosphate, the active cofactor of vitamin B6, is
dependent on riboflavin 5-phosphate, we propose a fast and simple ultra-high
performance liquid chromatography method for the simultaneous determination of
the native B6 vitamers pyridoxal, pyridoxine, pyridoxamine, their mono phosphorus
esters and 4-pyridoxic acid as well as vitamin B2 as riboflavin and its
phosphorus ester riboflavin 5-phosphate in milk. Separation was achieved under
6.0min by reversed-phase and pH gradient elution. Sample preparation was
optimized regarding various acids and pH levels. Changes in those parameters led
to significant deviations of sample matrix breakdown efficiency. The optimized
method was then validated regarding specificity, accuracy, precision, linearity,
range, detection and quantification limits. As the method performed satisfactory,
is was used to study commercial liquid cow's milk (n=31), regarding effects of
the employed preservation technique (pasteurization, extended shelf-life, ultra
high temperature) on the composition and content of B6 and B2 vitamers. In cow's
milk, vitamin B6 mostly consists of pyridoxal and its phosphate ester, with
pyridoxal phosphate being the bulk component. The catabolite of the vitamin B6
metabolism, 4-pyridoxic acid was present in significant amounts in all studied
samples, with up to 2.69MUmolL-1. Vitamin B2 was present as riboflavin and its
phosphate ester up to 12.86MUmolL-1.
PMID- 28420531
TI - High-throughput determination of vancomycin in human plasma by a cost-effective
system of two-dimensional liquid chromatography.
AB - Therapeutic drug monitoring (TDM) is one of the most important services of
clinical laboratories. Two main techniques are commonly used: the immunoassay and
chromatography method. We have developed a cost-effective system of two
dimensional liquid chromatography with ultraviolet detection (2D-LC-UV) for high
throughput determination of vancomycin in human plasma that combines the
automation and low start-up costs of the immunoassay with the high selectivity
and sensitivity of the liquid chromatography coupled with mass spectrometric
detection without incurring their disadvantages, achieving high cost
effectiveness. This 2D-LC system offers a large volume injection to provide
sufficient sensitivity and uses simulated gradient peak compression technology to
control peak broadening and to improve peak shape. A middle column was added to
reduce the analysis cycle time and make it suitable for high-throughput routine
clinical assays. The analysis cycle time was 4min and the peak width was 0.8min.
Compared with other chromatographic methods that have been developed, the
analysis cycle time and peak width for vancomycin was reduced significantly. The
lower limit of quantification was 0.20MUg/mL for vancomycin, which is the same as
certain LC-MS/MS methods that have been recently developed and validated. The
method is rapid, automated, and low-cost and has high selectivity and sensitivity
for the quantification of vancomycin in human plasma, thus making it well-suited
for use in hospital clinical laboratories.
PMID- 28420532
TI - Predictive Protein Toxicity and Its Use in Risk Assessment.
AB - In the EU novel proteins used in food or feed are assessed for their potential
toxic effects in humans and livestock animals. The discovery of clear molecular
features linked to the toxicity of a protein may be an important step towards the
use of predictive protein toxicity in risk assessment.
PMID- 28420533
TI - Observer-based consensus of networked thrust-propelled vehicles with directed
graphs.
AB - In this paper, we investigate the consensus problem for networked underactuated
thrust-propelled vehicles (TPVs) interacting on directed graphs. We propose
distributed observer-based consensus protocols, which avoid the reliance on the
measurements of translational velocities and accelerations. Using the input
output analysis, we present necessary and sufficient conditions to ensure that
the observer-based protocols can achieve consensus for both the cases without and
with constant communication delays, provided that the communication graph
contains a directed spanning tree. Simulation examples are finally provided to
illustrate the effectiveness of the control schemes.
PMID- 28420534
TI - Adaptive compensation control for attitude adjustment of quad-rotor unmanned
aerial vehicle.
AB - A compensation control strategy based on adaptive back-stepping technique is
presented to address the problem of attitude adjustment for a quad-rotor unmanned
aerial vehicle (QR- UAV) with inertia parameter uncertainties, the limited
airflow disturbance and the partial loss of rotation speed effectiveness. In the
design process of control system, adaptive estimation technique is introduced
into the closed loop system in order to compensate the lumped disturbance term.
More specifically, the designed controller utilizes "prescribed performance
bounds" method, and therefore guarantees the transient performance of tracking
errors, even in the presence of the lumped disturbance. Adaptive compensation
algorithms under the proposed closed loop system structure are derived in the
sense of Lyapunov stability analysis such that the attitude tracking error
converge to a small neighborhood of equilibrium point. Finally, the simulation
results demonstrate the effectiveness of the proposed controller.
PMID- 28420535
TI - Technique for myocardial protection in pulmonary atresia intact ventricular
septum.
PMID- 28420536
TI - Malperfusion rather than merely timing of operative repair determines early and
late outcome in type A aortic dissection.
AB - BACKGROUND: Although generally better outcomes are reported in patients
undergoing early repair of type A aortic dissection, patients who survive the
first 48 hours self-select themselves toward better outcomes as well.
Malperfusion is another important determinant of outcome in these patients. The
aim of this study was to examine the hypothesis that malperfusion, not the timing
of operation, is the dominant determinant of outcome in repair of type A aortic
dissection. METHODS: A total of 205 patients underwent operative repair of acute
type A aortic dissection in our hospital over a 17-year period. The time from
symptom onset to surgical repair was reliably established in 152 cases. Patients
were grouped into those who had undergone surgery within 12 hours of symptom
onset (early surgery group; n = 72 [47%]) and those who underwent surgery beyond
12 hours of symptom onset (late surgery group; n = 80 [53%]). RESULTS: Thirty-day
mortality was similar in the 2 groups (early surgery: 19.4% [95% confidence
interval [CI] 12.0%-30.6%]; late surgery: 13.8% [95% CI, 7.9%-23.5%]; P = .08).
The log-rank test for equality of survivor functions was 0.08. However,
malperfusion with hemodynamic compromise was more common in the early surgery
group (47% vs 31%; P = .029) and was identified as an independent predictor of
long-term mortality (hazard ratio, 2.65; 95% CI, 1.21-5.79; P = .014).
CONCLUSIONS: Malperfusion at presentation rather than timing of intervention is
the major risk factor of death both in the hospital and at long-term follow-up in
patients undergoing surgery for type A aortic dissection.
PMID- 28420537
TI - Bilateral versus unilateral antegrade cerebral perfusion in total arch
replacement for type A aortic dissection.
AB - BACKGROUND: Antegrade cerebral perfusion (ACP) is the most widely used cerebral
protection strategy for complex aortic repair and includes unilateral (u-ACP) and
bilateral (b-ACP) techniques. The superiority of b-ACP over u-ACP has been the
subject of much debate. Focusing on type A aortic dissection requiring total arch
replacement, we investigated the clinical effects of b-ACP versus u-ACP. METHODS:
Between September 2006 and August 2014, 203 patients presenting with type A
aortic dissection (median age, 51.0 +/- 13 years; range, 17-72 years; 128 males)
underwent total aortic arch replacement with hypothermic circulatory arrest. ACP
was used in all patients, including u-ACP in 82 (40.3%) and b-ACP in 121 (59.7%).
RESULTS: There was no significant difference between the u-ACP and b-ACP groups
in terms of cardiopulmonary bypass (CPB) time, cross-clamp time, or circulatory
arrest time. Overall 30-day mortality was comparable in the 2 groups (11.6% for b
ACP vs 20.7% for u-ACP; P = .075). The prevalence of postoperative permanent
neurologic dysfunction (PND) was comparable as well (8.4% vs 16.9%; P = .091).
Mean ventilation time was lower in the b-ACP group (95.5 +/- 45.25 hours vs 147.0
+/- 82 hours; P < .001). Mean lengths of stay in the intensive care unit and the
hospital overall were comparable in the 2 groups (intensive care unit: 16 +/-
17.75 days vs 17 +/- 11.5 days, P = .454; hospital: 26.5 +/- 20.6 days vs 24.8 +/
10.3 days, P = .434). The P values from logistic regression models indicated
that in the 2 groups combined, CPB time and circulatory arrest time were
independent risk factors for both mortality and PND. CONCLUSIONS: In this, the
first published study focusing on the efficacy of u-ACP and b-ACP in total arch
replacement for type A aortic dissection, the b-ACP group did not demonstrate
significantly lower 30-day mortality or PND rate compared with the u-ACP group.
Future large-sample studies are warranted to thoroughly examine this critical
issue.
PMID- 28420538
TI - The impact on productivity of a hypothetical tax on sugar-sweetened beverages.
AB - OBJECTIVES: To quantify the potential impact of an additional 20% tax on sugar
sweetened beverages (SSBs) on productivity in Australia. METHODS: We used a multi
state lifetable Markov model to examine the potential impact of an additional 20%
tax on SSBs on total lifetime productivity in the paid and unpaid sectors of the
economy. The study population consisted of Australians aged 20 years or older in
2010, whose health and other relevant outcomes were modelled over their remaining
lifetime. RESULTS: The SSBs tax was estimated to reduce the number of people with
obesity by 1.96% of the entire population (437,000 fewer persons with obesity),
and reduce the number of employees with obesity by 317,000 persons. These effects
translated into productivity gains in the paid sector of AU$751 million for the
working-age population (95% confidence interval: AU$565 million to AU$954
million), using the human capital approach. In the unpaid sector, the potential
productivity gains amounted to AU$1172 million (AU$929 million to AU$1435
million) using the replacement cost method. These productivity benefits are in
addition to the health benefits of 35,000 life years gained and a reduction in
healthcare costs of AU$425 million. CONCLUSIONS: An additional 20% tax on SSBs
not only improves health outcomes and reduces healthcare costs, but provides
productivity gains in both the paid and unpaid sectors of the economy.
PMID- 28420539
TI - HTA and decision-making processes in Central, Eastern and South Eastern Europe:
Results from a survey.
AB - OBJECTIVE: To gain knowledge and insights on health technology assessment (HTA)
and decision-making processes in Central, Eastern and South Eastern Europe
(CESEE) countries. METHODS: A cross-sectional study was performed. Based on the
literature, a questionnaire was developed in a multi-stage process. The
questionnaire was arranged according to 5 broad domains: (i) introduction/country
settings; (ii) use of HTA in the country; (iii) decision-making process; (iv)
implementation of decisions; and (v) HTA and decision-making: future challenges.
Potential survey respondents were identified through literature review-with a
total of 118 contacts from the 24 CESEE countries. From March to July 2014, the
survey was administered via e-mail. RESULTS: A total of 22 questionnaires were
received generating an 18.6% response rate, including 4 responses indicating that
their institutions had no involvement in HTA. Most of the CESEE countries have
entities under government mandates with advisory functions and different
responsibilities for decision-making, but mainly in charge of the reimbursement
and pricing of medicines. Other areas where discrepancies across countries were
found include criteria for selecting technologies to be assessed, stakeholder
involvement, evidence requirements, use of economic evaluation, and timeliness of
HTA. CONCLUSIONS: A number of CESEE countries have created formal decision-making
processes for which HTA is used. However, there is a high level of heterogeneity
related to the degree of development of HTA structures, and the methods and
processes followed. Further studies focusing on the countries from which
information is scarcer and on the HTA of health technologies other than medicines
are warranted. CLASSIFICATION: Reviews/comparative analyses.
PMID- 28420540
TI - What do we mean when we talk about the Triple Aim? A systematic review of
evolving definitions and adaptations of the framework at the health system level.
AB - Notwithstanding important contributions of the Triple Aim, uncritical enthusiasm
regarding the implications of the framework may be leading to inconsistent use,
particularly when applied at the health system level, which goes beyond the
original positioning of the framework as a strategic organizing principle to
guide improvement initiatives at the organizational or local community level. We
systematically identified uses of the Triple Aim that extended beyond its
original intention to focus on uses at the whole health system level, to assess
convergence and divergence with the original definition. We also attempted to
identify consistencies in the way the Triple Aim was adapted for different
contexts and settings. Data sources were indexed databases, web search engines,
and international experts. Forty-seven articles were included in the analysis. We
found that the definition of the Triple Aim has been subject to important
modifications when the framework is used to define goals for whole health care
systems or globally. Despite widespread recognition of the name, what constitutes
the Triple Aim framework varies. We identified the need to consider the inclusion
of at least two additional aims of health care systems - the provider experience
of care, and the desire to achieve health equity for populations.
PMID- 28420541
TI - Stability of Lisfranc injury fixation in Thiel Cadavers: Is routine fixation of
the 1st and 3rd tarsometatarsal joint necessary?
AB - BACKGROUND: There is debate as to whether a home run screw (medial cuneiform to
2nd metatarsal base) combined with k-wire fixation of the 4th & 5th
tarsometatarsal joints is sufficient to stabilise Lisfranc injuries or if
fixation of the 1st and 3rd tarsometatarsal joints is also required. Unlike the
2nd, 4th and 5th tarsometatarsal joints, stabilisation of the 1st and 3rd
requires either intra-articular screw or an extra-articular plate which risk
causing chondrolysis and/or osteoarthritis. The aims of this cadaveric study were
to determine if routine fixation of the 1st and 3rd tarsometatarsal joints is
necessary and to determine if a distal to proximal home run screw is adequate.
METHODS: Using 8 Theil-embalmed specimens, measurements of tarsometatarsal joint
dorsal displacement at each ray (1st-5th) and 1st-2nd metatarsal gaping were made
during simulated weight bearing with sequential ligamentous injury and
stabilisation to determine the contribution of anatomical structures and fixation
to stability. RESULTS: At baseline, mean dorsal tarsometatarsal joint
displacement of the intact specimens during simulated weight bearing (mm) was:
1st: 0.14, 2nd: 0.1, 3rd:0, 4th: 0, 5th: 0.14. The 1st-2nd intermetatarsal gap
was 0mm. After transection of the Lisfranc ligament only, there was 1st-2nd
intermetatarsal gaping (mean 4.5mm), but no increased dorsal displacement. After
additional transection of all the tarsometatarsal joint ligaments, dorsal
displacement increased at all joints (1st: 4.5, 2nd: 5.1, 3rd: 3.6, 4th: 2, 5th:
1.3). Stabilisation with the home run screw and 4th and 5th ray k-wires virtually
eliminated all displacement. Further transection of the inter-metatarsal
ligaments increased mean dorsal displacement of the 3rd ray to 2.5mm. K-wire
fixation of the 3rd ray completely eliminated dorsal displacement. CONCLUSIONS:
The results of this cadaveric study suggest that stabilising the medial cuneiform
to the 2nd metatarsal base combined with stabilisation of the 4th and 5th
tarsometatarsal joints with K-wires will stabilise the 1st and 3rd
tarsometatarsal joints if the inter-metatarsal ligaments are intact. Thus 3rd
TMTJ stability should be checked after stabilising the 2nd and 4/5th. Provided
the intermetatarsal ligaments (3rd-4th) are intact, the 3rd ray does not need to
be routinely stabilised.
PMID- 28420542
TI - Improving prehospital trauma care in Rwanda through continuous quality
improvement: an interrupted time series analysis.
AB - INTRODUCTION: Injury is a major cause of premature death and disability in East
Africa, and high-quality pre-hospital care is essential for optimal trauma
outcomes. The Rwandan pre-hospital emergency care service (SAMU) uses an
electronic database to evaluate and optimize pre-hospital care through a
continuous quality improvement programme (CQIP), beginning March 2014. MATERIALS
AND METHODS: The SAMU database was used to assess pre-hospital quality metrics
including supplementary oxygen for hypoxia (O2), intravenous fluids for
hypotension (IVF), cervical collar placement for head injuries (c-collar), and
either splinting (splint) or administration of pain medications (pain) for long
bone fractures. Targets of >90% were set for each metric and daily team meetings
and monthly feedback sessions were implemented to address opportunities for
improvement. These five pre-hospital quality metrics were assessed monthly before
and after implementation of the CQIP. Met and unmet needs for O2, IVF, and c
collar were combined into a summative monthly SAMU Trauma Quality Scores (STQ
score). An interrupted time series linear regression model compared the STQ score
during 14 months before the CQIP implementation to the first 14 months after.
RESULTS: During the 29-month study period 3,822 patients met study criteria.
1,028 patients needed one or more of the five studied interventions during the
study period. All five endpoints had a significant increase between the pre-CQI
and post-CQI periods (p<0.05 for all), and all five achieved a post-CQI average
of at least 90% completion. The monthly composite STQ scores ranged from 76.5 to
97.9 pre-CQI, but tightened to 86.1-98.7 during the post-CQI period. Interrupted
time series analysis of the STQ score showed that CQI programme led to both an
immediate improvement of +6.1% (p=0.017) and sustained monthly improvements in
care delivery-improving at a rate of 0.7% per month (p=0.028). CONCLUSION: The
SAMU experience demonstrates the utility of a responsive, data-driven quality
improvement programme to yield significant immediate and sustained improvements
in pre-hospital care for trauma in Rwanda. This programme may be used as an
example for additional efforts engaging frontline staff with real-time data
feedback in order to rapidly translate data collection efforts into improved care
for the injured in a resource-limited setting.
PMID- 28420543
TI - Serum persistent organic pollutants (POPs) and prostate cancer risk: A case
cohort study.
AB - It is still unclear whether persistent organic pollutants (POPs) exposure
increases the prostate cancer incidence risk. This prospective cohort study
evaluated the associations between serum POPs concentrations and prostate cancer
risk. Within a case-cohort study, we identified 110 people diagnosed with
prostate cancer and randomly selected 256 sub-cohort participants without
prostate cancer. Serum concentrations of 32 polychlorinated biphenyl (PCB)
congeners and 19 organochlorine pesticides (OCPs) were measured. The hazard
ratios (HRs) and 95% confidence interval (95% CI) for determining the
associations between POPs and risk of prostate cancer were estimated using the
weighted Cox regression model. Compared to the lowest tertile, increased risks of
prostate cancer incidence were observed in the upper tertile of following PCBs:
the moderately chlorinated (HR: 4.19; 95% CI: 1.30-13.54), the highly chlorinated
(HR: 4.14; 95% CI: 1.75-9.79), biologically persistent as CYP1A and CYP2B
inducers (HR: 4.44; 95% CI: 1.33-14.83), the sum of non- dioxin-like (HR: 3.47;
95% CI: 1.21-9.98), and ?PCBs (HR: 4.29; 95% CI: 1.52-12.08). In dose-response
curves, ?PCBs was associated with the increased risk of prostate cancer. Our
findings suggested a possible role of POPs in the etiology of prostate cancer.
PMID- 28420544
TI - Disclosing Agents for the Intraoperative Identification of Biofilms on Orthopedic
Implants.
AB - BACKGROUND: Disclosing agents are dyes used in dentistry to colorize plaque
(biofilm) and may offer a means for intraoperative detection of biofilms on
orthopedic implants. Methylene blue (MB) stains biofilm and is safely used in
orthopedic applications. Injection of MB into acutely infected prosthetic knees
before debridement may enable visualization of biofilm, which could influence
treatment decisions. The aims of this study were to determine if MB could be used
to visualize biofilm on total knee arthroplasty (TKA) implants and to determine
if MB staining has an antimicrobial effect that might interfere with subsequent
culture. METHODS: Staphylococcus epidermidis biofilms were formed on TKA
polyethylene liners and polymethylmethacrylate (PMMA) and Teflon discs. After
staining biofilms on these implants, the bacterial densities were determined
through sonication and quantitative culture. The antimicrobial activity of MB
staining was determined by measuring the bacterial density of S. epidermidis
biofilms on PMMA discs incubated in 0.05% MB for 24 hours vs 30 seconds and
comparing it with controls unexposed to MB. RESULTS: MB stained S. epidermidis
biofilms grown on TKA implants and Teflon and PMMA discs in vitro. Sonication and
quantitative culture of the stained implants showed that bacterial densities were
at supraphysiological levels. Staining did not affect the ability to culture the
organism. CONCLUSION: MB is a possible cost-effective and novel method to
expeditiously identify intraoperative biofilm. To further evaluate MB staining
and its potential clinical usefulness, future studies are needed to assess the
ability of MB to stain physiological levels of biofilm.
PMID- 28420545
TI - GQSAR modeling and combinatorial library generation of 4-phenylquinazoline-2
carboxamide derivatives as antiproliferative agents in human Glioblastoma tumors.
AB - BACKGROUND: TSPO translocator protein, encoded in humans by the Tspo gene plays a
crucial role in mitochondria mediated apoptosis and necrotic cell death through
its association with Mitochondrial Permeability Transition pore (MPTP). It has
been shown that this function can be exploited as a potential treatment for human
Glioblastoma Multiforme. In this study, a novel robust fragment based QSAR model
has been developed for a series of 4-phenylquinazoline-2-carboxamides
experimentally known to be ligands for TSPO, thus triggering apoptotic mechanism
cascade. RESULTS: Model developed showed satisfactory statistical parameters for
the experimentally reported dataset (r2=0.8259, q2=0.6788, pred_r2=0.8237 and F
test=37.9). Low standard error values (r2_se=0.253, q2_se=0.34, pred_r2_se=0.14)
confirmed the accuracy of the generated model. The model obtained had 4
descriptors, namely, R1-Volume, R2-SsCH3E-index, R3-SsCH3count and R5-EpsilonR.
Two of them had positive contribution while the other two had negative
correlation. CONCLUSION: The high binding affinity and the presence of essential
structural features in these compounds make them an ideal choice for the
consideration as potent anti-GBM drugs. Activity predicted by GQSAR model
reinforces their potential as worthy candidates for drugs against GBM. The
detailed analysis carried out in this study provides a substantial basis for the
prospective design and development of novel 4-phenylquinazoline-2-carboxamide
compounds as TSPO ligands capable of inducing apoptosis in cancer cells.
PMID- 28420546
TI - Facilitating Fresh: State Laws Supporting School Gardens Are Associated With Use
of Garden-Grown Produce in School Nutrition Services Programs.
AB - OBJECTIVE: To examine whether state laws are associated with the presence of
school gardens and the use of garden-grown produce in school nutrition services
programs. DESIGN: Nationally representative data from the School Health Policies
and Practices Study 2014 were combined with objectively coded state law data
regarding school gardens. MAIN OUTCOME MEASURES: Outcomes were: (1) the presence
of a school garden at each school (n = 419 schools), and (2) the use of garden
grown items in the school nutrition services program. ANALYSIS: Multivariate
logistic regression was used to examine each outcome. Contextual covariates
included school level, size, locale, US Census region, student race/ethnic
composition, and percentage of students eligible for free and reduced-priced
meals. RESULTS: State law was not significantly associated with whether schools
had a garden, but it was associated with whether schools used garden-grown items
in nutrition services programs (odds ratio, 4.21; P < .05). Adjusted prevalence
of using garden-grown items in nutrition services programs was 15.4% among
schools in states with a supportive law, vs 4.4% among schools in states with no
law. CONCLUSIONS AND IMPLICATIONS: State laws that support school gardens may
facilitate the use of garden-grown items in school nutrition service programs.
Additional research is needed regarding the types of messaging that might be most
effective for motivating school administrators to appreciate the value of school
gardens. In addition, another area for further research pertains to scaling
garden programs for broader reach.
PMID- 28420547
TI - Types and Characteristics of Fish and Seafood Provisioning Scripts Used by Rural
Midlife Adults.
AB - OBJECTIVE: To examine rural New York State consumers' cognitive scripts for fish
and seafood provisioning. DESIGN: A cross-sectional design with in-depth,
semistructured interviews. SETTING: Three rural New York State counties.
PARTICIPANTS: Adults (n = 31) with diverse fish-related experiences were
purposefully recruited. PHENOMENON OF INTEREST: Scripts describing fish and
seafood acquisition, preparation, and eating out. ANALYSIS: Interview transcripts
were coded for emergent themes using Atlas.ti. Diagrams of scripts for each
participant were constructed. RESULTS: Five types of acquisition scripts included
quality-oriented, price-oriented, routine, special occasion, and fresh catch.
Frequently used preparation scripts included everyday cooking, fast meal,
entertaining, and grilling. Scripts for eating out included fish as first choice,
Friday outing, convenient meals, special event, and travel meals. Personal values
and resources influenced script development. Individuals drew on a repertoire of
scripts based on their goals and resources at that time and in that place. Script
characteristics of scope, flexibility, and complexity varied widely. CONCLUSIONS
AND IMPLICATIONS: Scripts incorporated goals, values, and resources into routine
food behaviors. Understanding the characteristics of scripts provided insights
about fish provisioning and opportunities to reduce the gap between current
intake and dietary guidelines in this rural setting.
PMID- 28420548
TI - Expression of long non-coding RNAs in autoimmunity and linkage to enhancer
function and autoimmune disease risk genetic variants.
AB - Genome-wide association studies have identified numerous genetic variants
conferring autoimmune disease risk. Most of these genetic variants lie outside
protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also
differentially expressed in autoimmune disease but their regulation is also
unclear. The majority of the human genome is transcribed yet its biologic
significance is incompletely understood. We performed whole genome RNA-sequencing
[RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs
[lncRNAs] in leukocytes from subjects with autoimmune disease and identified
annotated and novel lncRNAs differentially expressed across multiple disorders.
We found that loci transcribing novel lncRNAs were not randomly distributed
across the genome but co-localized with leukocyte transcriptional enhancers,
especially super-enhancers, and near genetic variants associated with autoimmune
disease risk. We propose that alterations in enhancer function, including lncRNA
expression, produced by genetics and environment, change cellular phenotypes
contributing to disease risk and pathogenesis and represent attractive
therapeutic targets.
PMID- 28420549
TI - Predictors of Left Ventricular Functional Recovery and Their Impact on Clinical
Outcomes in Patients With Newly Diagnosed Dilated Cardiomyopathy and Heart
Failure.
AB - BACKGROUND: To identify the predictors of left ventricular functional recovery
(LVFR) and its impacts on clinical outcomes in acute heart failure (AHF) patients
with newly diagnosed dilated cardiomyopathy (DCM). METHODS: A total of 175
consecutive patients with newly diagnosed DCM and AHF were divided into two
groups according to LVFR on FU echocardiography; the recovered group (n=54,
54.3+/-18.5years, 31 males) vs. the non-recovered group (n=121, 60.5+/-15.1years,
79 males). Clinical, laboratory, and echocardiographic findings were compared,
and major adverse cardiac and cerebrovascular events (MACCE) including death,
rehospitalisation, and stroke were analysed. RESULTS: Left ventricular function
(LV) was normalised in 54 patients (30.8%) on follow-up echocardiography. The
change in the level of N-terminal pro-B-type natriuretic peptide (DeltaNT-proBNP)
between initial presentation and discharge >1633.5pg/mL was an independent
predictor of LVFR, whereas diabetes and LV end-systolic diameter >50mm were
negative predictors of LVFR on multivariate analysis. During five years of
clinical follow-up, MACCE developed in 91 patients: 58 deaths, 29
rehospitalisations, and 4 strokes. On multivariate analysis, baseline LVEF <30%
and no LVFR were independent predictors of MACCE. CONCLUSION: Left ventricular
functional recovery was not uncommon in newly diagnosed DCM with AHF. The changes
in NT-proBNP level during hospitalisation, diabetes, and larger initial LV size
were independent predictors of LVFR, and LVFR was an independent predictor of
future MACCE. Serial monitoring of NT-proBNP and LV function would be useful in
the risk stratification of newly diagnosed DCM with AHF.
PMID- 28420550
TI - Effect of a moderate caffeine dose on endurance cycle performance and
thermoregulation during prolonged exercise in the heat.
AB - OBJECTIVES: This study investigated the influence of a moderate caffeine dose on
endurance cycle performance and thermoregulation during prolonged exercise in
high ambient temperature. DESIGN: Double-blind cross-over study. METHODS: Eight
healthy, recreationally active males (mean+/-SD; age: 22+/-1 years; body mass:
71.1+/-8.5kg; VO2peak: 55.9+/-5.8mLkg-1min-1; Wmax: 318+/-37W) completed one
VO2peak test, one familiarisation trial and two experimental trials. After an
overnight fast, participants ingested a placebo or a 6mgkg-1 caffeine dose 60min
before exercise. The exercise protocol consisted of 60min of cycle exercise at
55% Wmax, followed by a 30min performance task (total kJ produced) in 30 degrees
C and 50% RH. RESULTS: Performance was enhanced (Cohen's d effect size=0.22) in
the caffeine trial (363.8+/-47.6kJ) compared with placebo (353.0+/-49.0kJ;
p=0.004). Caffeine did not influence core (p=0.188) or skin temperature (p=0.577)
during exercise. Circulating prolactin (p=0.572), cortisol (p=0.842) and the
estimated rates of fat (p=0.722) and carbohydrate oxidation (p=0.454) were also
similar between trial conditions. Caffeine attenuated perceived exertion during
the initial 60min of exercise (p=0.033), with no difference in thermal stress
across trials (p=0.911). CONCLUSIONS: Supplementation with 6mgkg-1 caffeine
improved endurance cycle performance in a warm environment, without
differentially influencing thermoregulation during prolonged exercise at a fixed
work-rate versus placebo. Therefore, moderate caffeine doses which typically
enhance performance in temperate environmental conditions also appear to benefit
endurance performance in the heat.
PMID- 28420551
TI - Is There an Accurate Pre-operative Criterion for Dialysis Access Artery or Vein
diameter?
PMID- 28420552
TI - Commentary on "Five Year Natural History of Screening Detected Sub-Aneurysms and
Abdominal Aortic Aneurysms in 70 Year Old Women and Systematic Review of Repair
Rate in Women".
PMID- 28420553
TI - Incidence of respiratory viral infections and associated factors among children
attending a public kindergarten in Taipei City.
AB - BACKGROUND: Kindergarteners frequently encounter various infectious diseases, so
surveillance of viral infectious diseases would provide information for their
health promotion. METHODS: We enrolled kindergarten attendees, age 2-5 years,
during the academic years of 2006 and 2007 in a Taipei City kindergarten. Daily
monitoring of illness and regular biweekly physical examinations were undertaken.
Multiple infections were defined as one child having two or more laboratory
confirmed viral infections with different viruses or different serotypes during
one academic year. RESULTS: The overall laboratory-confirmed incidence rate of
respiratory viral infection was 239 per 100 person-years in the 2006 academic
year and 136 per 100 person-years in the 2007 academic year. The attack rate for
seasonal influenza was 17% in the 2006 academic year and 27% in the 2007 academic
year. Boys and children with allergies had significantly higher risks to get
multiple viral infections [odds ratio (OR) 1.81, 95% confidence interval (CI)
1.20-2.75; OR 1.56, 95% CI 1.00-2.39, respectively]. Boys also tended to get
enterovirus infections (OR 1.56, 95% CI 1.02-2.38) while children with allergies
tended to acquire adenovirus infections (OR 1.71, 95% CI 1.12-2.66). CONCLUSION:
Boys and children with allergies were more susceptible to multiple viral
infections, so they should be more cautious about viral infections.
PMID- 28420554
TI - The incidence and clinical associated factors of interval colorectal cancers in
Southern Taiwan.
AB - BACKGROUND/PURPOSE: Interval colorectal cancer (CRC) is an emerging issue in CRC
screening and surveillance. The frequency of interval CRC and its associated
factors have not been well studied in Eastern Asia. We aim to clarify the factors
associated with interval CRC. METHODS: CRC patients who had negative colonoscopy
results 6-36 months prior to cancer diagnosis were defined as cases of interval
CRC. Patient characteristics, past history, colon preparation, colonoscopy
findings, and pathology were retrospectively evaluated. A total of 670 patients
with colorectal adenocarcinoma by pathology who also underwent colonoscopy before
diagnosis from January 2005 to November 2014 were recruited. RESULTS: Twenty-two
(3.28%) patients (65.7 +/- 9.2 years old; 9 male) were diagnosed with interval
CRC. The interval CRCs were predominantly located at the rectum and cecum, and
presented as earlier stage cancers (Stage I and Stage II: 86.4%, Stage III and
Stage IV: 13.6%). Factors associated with interval cancer include end-stage renal
disease (ESRD) (hazard ratio: 10.494, 95% confidence interval: 2.131-51.681) and
shorter ascending colon withdrawal time (interval cancer: noninterval cancer
2.00+/-0.82: 4.91+/-3.74 minutes; hazard ratio: 0.561, 95% confidence interval:
0.345-0.913). Prior polypectomy and tumor size also tended to be related to
interval CRC. CONCLUSION: The prevalence of interval CRC in the present study is
3.28%. Comorbidity with ESRD and shorter ascending colon withdrawal time could be
factors associated with interval CRC. Good colon preparation for the patients
with ESRD and more ascending colon withdrawal time could reduce the interval CRC.
PMID- 28420555
TI - Chemoembolization for Hepatocellular Carcinoma in Patients with Extrahepatic
Spread: Prognostic Determinants and Appropriate Candidates.
AB - PURPOSE: To investigate treatment outcome, prognostic factors for overall
survival, and appropriate candidates for transarterial chemoembolization among
patients with hepatocellular carcinoma (HCC) and extrahepatic spread (EHS).
MATERIALS AND METHODS: From January 2010 to June 2014, 111 consecutive patients
with HCC and EHS treated by transarterial chemoembolization alone were evaluated.
Factors associated with overall survival were evaluated using Cox regression
analysis, and a scoring equation was established to subgroup patients with EHS.
RESULTS: Median follow-up was 3.8 months, and median overall survival was 3.8
months (95% confidence interval [CI], 2.9-4.7 months). Multivariate analysis
demonstrated maximum tumor size >= 10 cm (hazard ratio [HR] 1.58; 95% CI, 1.02
2.46; P = .041), multifocal intrahepatic tumors (HR 1.55; 95% CI, 1.03-2.33; P =
.037), and portal vein tumor thrombosis (PVTT) (HR 1.81; 95% CI, 1.12-2.91; P =
.015) as significant predictors of overall survival. Based on these factors, a
scoring equation was developed to predict treatment outcome of transarterial
chemoembolization, with an area under the receiver operating characteristic curve
of 0.76 in predicting 6-month survival. Using a cutoff score of 5.5, patients
with HCC and EHS were divided into 2 groups with significantly different overall
survival (8.1 months for EHS1 and 2.4 months for EHS2; P < .001). The described
method of subgrouping remained discriminatory regardless of baseline
characteristics. CONCLUSIONS: Maximum tumor size, intrahepatic tumor
distribution, and presence of PVTT were significant determinants of overall
survival for patients with HCC and EHS. Transarterial chemoembolization may be
appropriate for patients with EHS but lower intrahepatic tumor burden.
PMID- 28420556
TI - Can paddock scale data integration achieve more cost effective outcomes in the
Great Barrier Reef? A case study in the Fitzroy Basin.
AB - The decline in health of the Great Barrier Reef and the pressure on allocating
funds efficiently has increased efforts to prioritise where public funds are
invested. The Fitzroy basin and coastal catchments is 152,000 square kilometres
and geographically diverse. Past work has identified that sediment loads leaving
the catchment are posing a high risk to the ongoing health of the Reef and that
there is a need to prioritise funds to achieve cost effective outcomes. In this
paper we aim to present an alternative approach to effective prioritisation of
sediment reductions. The approach integrates spatial information regarding the
sediment source and process, levels of adoption, bare ground cover, and cost into
a function to rank neighbourhood catchments. The results demonstrate the
complexity of the issue and the challenge the Fitzroy Basin Association faces
when allocating funds. They also illustrate that there are effective
opportunities in particular priority areas within the catchment in which on
ground actions could be undertaken, proving it to be a useful approach in
prioritising future investments aimed at achieving cost effective sediment
reductions to the Reef.
PMID- 28420557
TI - Temporal and Spatial View of Jasmonate Signaling.
AB - The jasmonate signaling pathway has been established for 10 years. Nonetheless,
two recent reports suggest that its temporal and spatial regulation is worth
further investigation. These reports show that jasmonate responses decay
gradually with increasing plant age and that signaling components vary between
different tissues.
PMID- 28420558
TI - Maternal Medical Complexity: Impact on Prenatal Health Care Spending among Women
at Low Risk for Cesarean Section.
AB - BACKGROUND: Obstetric procedures are among the most expensive health care
services, yet relatively little is known about health care spending among
pregnant women, particularly the commercially-insured. OBJECTIVE: The objective
of this study was to examine the association between maternal medical complexity,
as a result of having one or more comorbid conditions, and health care spending
during the prenatal period among a national sample of 95,663 commercially-insured
women at low risk for cesarean delivery. METHODS: We conducted secondary analyses
of 2010-2011 inpatient, outpatient, and professional claims for health care
services from the Health Care Cost Institute. Allowed charges were summed for the
prenatal and childbirth periods. Ordinary least squares regressions tested
associations between maternal health conditions and health care expenditures
during pregnancy. RESULTS: Thirty-four percent of pregnant women had one or more
comorbidities; 8% had two or more. Pregnant women with one or more comorbidities
had significantly higher allowed charges than those without comorbidities (p <
.001). Spending during the prenatal period was nearly three times higher for
women with preexisting diabetes compared with women with no comorbid conditions.
Average levels of prenatal period spending associated with maternal comorbidities
were similar for women who had vaginal and cesarean deliveries. Patient
characteristics accounted for 30% of the variance in prenatal period
expenditures. CONCLUSIONS: The impact of maternal comorbidities, and in
particular preexisting diabetes, on prenatal care expenditures should be taken
into account as provider payment reforms, such as pay-for performance incentives
and bundled payments for episodes of care, extend to maternal and child health
related services.
PMID- 28420559
TI - Recent trends in the prevalence of underweight, overweight, and obesity in Korean
adults: The Korean National Health and Nutrition Examination Survey from 1998 to
2014.
AB - BACKGROUND: Recent obesity studies have reported that the rising trend in obesity
has stabilized or leveled off. Our study aimed to update estimates of the recent
prevalence trend in obesity based on the Korean National Health and Nutrition
Examination Survey 1998-2014. METHODS: A total of 66,663 subjects were included
and defined as being either underweight, overweight, or obese, in accordance with
a BMI of 18.5 kg/m2 or lower, 23 kg/m2 or higher, and 25 kg/m2 or higher,
respectively. RESULTS: The prevalence of underweight in KNHANES I through VI
surveys was 4.7%, 3.3%, 3.4%, 3.3%, 2.7%, and 2.6%, respectively, in men (P for
trend = 0.03, beta = -0.002) and 5.4%, 6.1%, 5.8%, 6.5%, 7.6%, and 7.5%,
respectively, in women (P for trend = 0.04, beta = 0.003). Also for KNHANES I
through VI, the respective prevalence of overweight/obesity was 50.3%, 57.2%,
62.5%, 62.3%, 61.4%, and 62.3% in men (p for trend<0.01, beta = 0.009) and 48.3%,
50.3%, 50.0%, 47.8%, 47.0%, and 45.3% in women (p for trend<0.01, beta = -0.01),
respectively. CONCLUSIONS: The obesity occurrence in men was trending upward with
respect to overweight/obesity and for grade 1 and 2 obesity, but not for
abdominal obesity. However, the obesity trends in women were leveling off from
overweight/obesity, grade 1 obesity, and abdominal obesity measures. Further
studies are required with data on muscle mass and adiposity for effective obesity
control policies.
PMID- 28420560
TI - Does revision of resection margins based on frozen section improve overall
survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma? A
meta-analysis.
AB - BACKGROUND: Margin status is the main surgical determinant of long-term outcome
in pancreatic cancer. Intraoperative frozen section (IOFS) detects microscopic
positive margins at a stage when margin revision is possible. The aim of this
study was to determine if IOFS driven-revision of pancreatic resection margin(s)
improves overall survival (OS) in pancreatic cancer. METHODS: A systematic review
of major reference databases was undertaken. Patients were divided into 3 groups
based on initial FS (FSR0 for negative margin and FSR1 for positive microscopic
margin) and final Permanent Section report (PSR0 for negative margin and PSR1 for
positive microscopic margin): Group 1 (FSR0 -> PSR0), Group 2 (FSR1 -> PSR0), and
Group 3 (FSR1 -> PSR1). Patients in Groups 2 and 3 had surgical revision of the
FSR1 margin. Data was meta-analysed. RESULTS: 4 studies included in the final
analysis. No difference in OS and incidence of lymph node metastases between
Groups 2 and 3 (P = 0.590 and P = 0.410). CONCLUSIONS: IOFS-based revision of R1
pancreatic resection margin does not improve OS, even when it results in an R0
margin. This suggests that any benefit of margin revision based on FS is over
ridden by markers of more advanced or aggressive disease.
PMID- 28420561
TI - Response to Gentile S et al.: Risk factors for severe hypoglycaemia in people
with insulin-treated diabetes: Are we sure we took into account all variables
involved?
PMID- 28420562
TI - Progression of untreated mild thoracic Scheuermann's kyphosis - Radiographic and
functional assessment after mean follow-up of 46 years.
AB - BACKGROUND: There is no data available on the radiographic development of the
Scheuermann's deformity. Our purpose was to investigate radiographic deformity
progression and the relation between kyphosis progression and clinical outcome in
patients with untreated Scheuermann's kyphosis. METHODS: Thoracic kyphosis (Th4
Th12) was measured from standing lateral radiographs in 19 patients at baseline
and after mean 46-year follow-up. Mean age at baseline was 19.2 and at follow-up
64.7 years. At follow-up, height, weight, hand grip strength, and hamstring
tightness were measured, and sit-to-stand and walking tests were performed.
Additionally general health and quality of life questionnaires were administered.
RESULTS: The mean thoracic kyphosis increased from 46 degrees (range 25 degrees
78 degrees ) at baseline to 60 degrees (34 degrees -82 degrees ) (p < 0.001) at
follow-up. Mean of the vertebrae wedge increased from 8.8 degrees to 9.9 degrees
(p = 0.046). There was no correlation between extent of kyphosis progression and
function at follow-up. CONCLUSIONS: Among patients with Scheuermann's disease the
degree of radiographic deformity progressed slightly during long-term follow-up.
Progression did not predict symptoms.
PMID- 28420563
TI - Compassion, Mindfulness, and the Happiness of Healthcare Workers.
AB - CONTEXT: Decreased well-being of healthcare workers expressed as stress and
decreased job satisfaction influences patient safety, patient satisfaction, and
cost containment. Self-compassion has garnered recent attention due to its
positive association with well-being and happiness. Discovering novel pathways to
increase the well-being of healthcare workers is essential. OBJECTIVE: This study
sought to explore the influence of self-compassion on employee happiness in
healthcare professionals. DESIGN, SETTING, AND PARTICIPANTS: A total of 400
participants (mean age = 45 +/- 14, 65% female) healthcare workers at a large
teaching hospital were randomly asked to complete questionnaires assessing their
levels of happiness and self-compassion, life conditions, and habits. MEASURES:
Participants completed the Happiness Scale and Self-Compassion Scales, the Five
Facet Mindfulness Questionnaire as well as variables associated with well-being:
relationship status, the number of hours spent exercising a week, attendance at a
wellness facility, and engagement in a regular spiritual practice. RESULTS: Self
compassion was significantly and independently associated with perceived
happiness explaining 39% of its variance after adjusting for age, marital status,
gender, time spent exercising, and attendance to an exercise facility. Two
specific subdomains of self-compassion from the instrument used, coping with
isolation and mindfulness, accounted for 95% of the self-compassion effect on
happiness. CONCLUSION: Self-compassion is meaningfully and independently
associated with happiness and well-being in healthcare professionals. Our results
may have practical implications by providing specific self-compassion components
to be targeted in future programs aimed at enhancing well-being in healthcare
professionals.
PMID- 28420564
TI - Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Primary Non-muscle-invasive
Bladder Cancer.
AB - INTRODUCTION: The purpose of this study was to assess the role of pretreatment
neutrophil-to-lymphocyte ratio (NLR) as a predictor of clinical outcomes in
patients treated with transurethral resection (TURB) for primary non-muscle
invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Data from 918 patients
treated with TURB for primary NMIBC were retrospectively collected. NLR was
evaluated as binary variable with the cut-point of 3 based on the visual best
correlation of the receiver operating curve analyses focusing on disease
recurrence. The median follow-up was 62 months. Cox regression analyses were used
to evaluate associations with recurrence (RFS) and progression-free survival
(PFS). Subgroup analyses were done according to risk groups and receipt of
intravesical bacillus Calmette-Guerin therapy. RESULTS: Overall, 293 patients had
a NLR >= 3. High NLR was associated with pathologic T stage and smoking status.
The 5-year RFS and PFS for NLR < 3 and NLR >= 3 were, respectively, 55.5% versus
45.9% (P = .01) and 94.9% versus 89.9% (P = .004). On multivariable analyses, NLR
>= 3 remained significantly associated with RFS and PFS. The addition of NLR
increased the discrimination of a multivariable model by 0.6% and 2.3% for RFS
and PFS, respectively. Moreover, NLR showed a trend in the association with
outcomes in patients treated with intravesical bacillus Calmette-Guerin therapy.
CONCLUSIONS: Integration of NLR in a prediction model could be helpful in
predicting RFS and PFS in patients with primary NMIBC and identifying those who
are likely to fail therapy and may benefit from an early radical cystectomy.
Limitations are associated to the retrospective design.
PMID- 28420566
TI - The role of antithrombin in patients with toxic epidermal necrolysis.
PMID- 28420565
TI - Analysis of prognostic factors for acute kidney injury with continuous renal
replacement therapy in severely burned patients.
AB - BACKGROUND: Acute kidney injury (AKI) is a critical complications in severely
burned patients associated with high morbidity and mortality. The purpose of this
study was to investigate the impact of severity of AKI at the time of continuous
renal replacement therapy (CRRT) start on patient outcome and to identify the
prognostic factors in severely burned patients with CRRT application. METHODS:
From January 2007 to June 2010, 84 burn patients with more than 40% of total body
surface area (TBSA) burned who treated with continuous renal replacement therapy
for acute kidney injury were analyzed retrospectively. RESULTS: There was no
significant difference of mortality by the severity of AKI at the time of CRRT
start. However, the mean TBSA burned, abbreviated burn severity index, arterial
pH, partial pressure of carbon dioxide (PaCO2) and blood urea nitrogen
(BUN)/creatinine (Cr) ratio had a statistical significance to predict mortality
in receiver operation characteristic curve. In a multivariate logistic regression
analysis, only sepsis had an independent association with mortality. CONCLUSIONS:
The severity of the AKI at the time of CRRT start did not have significant
relationship with patient outcome. CRRT can be applied to minimize the
complication of AKI including electrolyte imbalance and volume overload. Because
only the presence of sepsis was independently associated with mortality,
treatment for sepsis should be focused to improve the survival of the severely
burned patients with CRRT.
PMID- 28420567
TI - A draft of bronchoscopic grading system in patients with toxic epidermal
necrolysis.
PMID- 28420568
TI - Gender-specific differences and burn outcome.
PMID- 28420569
TI - Identification of factors predicting scar outcome after burn in adults: A
prospective case-control study.
AB - This study examined influences on scarring after burn in a prospective study
using a defined outcome measure: scar height measured by a modified Vancouver
Scar Scale (mVSS). A prospective case-control study was conducted among 616 adult
subjects who sustained a burn in Western Australia. Patient factors influencing
scar outcome including gender, Fitzpatrick skin type and selected co-morbidities
were explored, as well as injury and clinical factors. A logistic regression
model for raised scar after burn was developed which achieved an overall correct
prediction rate of 81.1%; 74.8% for those with raised scar and 86.0% for those
without raised scar. From this study, injury and clinical predictors for raised
scar after adjustment for other variables are: increasing %TBSA, greater burn
depth as indicated by level of surgical intervention, wound complications and
prolonged hospital stay. Intrinsic patient predictors for raised scar in patients
with comparable injuries are: young age (<=30 years), female gender and
Fitzpatrick skin types 4-6. The strength of association statistics (odds ratios
and 95% confidence intervals) reported will be of practical benefit for clinical
decision-making and counselling of patients, and plausible biological
explanations for the findings support the validity of the results.
PMID- 28420570
TI - Herpesviradae infections in severely burned children.
AB - OBJECTIVE: Burn-related immunosuppression can promote human herpesviridae
infections. However, the effect of these infections on morbidity and mortality
after pediatric burn injuries is unclear. METHODS: We retrospectively analyzed
pediatric patients with burns >=10% of the total body surface area (TBSA) who
were admitted between 2010 and 2015. On clinical suspicion of a viral infection,
antiviral therapy was initiated. Viral infection was confirmed via Tzanck smear,
viral culture, and/or PCR. Study endpoints were mortality, days of antiviral
agent administration, type of viral test used, type of viral infection, and
length of hospitalization. RESULTS: Of the 613 patients were analyzed, 28
presented with clinically diagnosed viral infections. The use of Tzanck smears
decreased over the past 5 years, whereas PCR and viral cultures have become
standard. Patients with viral infections had significantly larger burns (53+/-15%
vs. 38+/-18%, p<0.001); however, length of stay per TBSA burn was comparable
(0.5+/-0.4 vs. 0.6+/-0.2, p=0.211). The most commonly detected herpesviridae was
herpes simplex virus 1. Two patients died due to sepsis, which was accompanied by
HSV infection. The mortality rate among all patients (2.7%) was comparable to
that in the infected group (7.1%, p=0.898). Acyclovir was given systemically for
9+/-8days (N=76) and/or topically for 9+/-9days for HSV (N=39, combination of
both N=33). Ganciclovir was prescribed in three cases for CMV. CONCLUSIONS: Viral
infections occur more commonly in patients suffering from larger burns, and HSV
infections can contribute to mortality.
PMID- 28420571
TI - Assessing guidelines for burn referrals in a resource-constrained setting:
Demographic and clinical factors associated with inter-facility transfer.
AB - AIM: The aim was to assess demographic and clinical factors associated with inter
facility referrals for patients with burns in a resource-constrained setting.
METHODS: This was a cross-sectional case review of patients presenting with a
burn at the trauma unit at the Red Cross War Memorial Children's Hospital (RXH)
in Cape Town, South Africa. RESULTS: Six hundred and eleven-(71%) children were
referred to the burns or the intensive care unit and 253 children were treated
and discharged from the trauma unit. Of those admitted as inpatients 94%
fulfilled at least one of the criteria for referral and 80% of those treated and
discharged fulfilled the criteria for referral. CONCLUSIONS: Almost three out of
four children evaluated at the trauma unit were referred to the burns unit for
further management. However, a large number of patients were treated and
discharged from the trauma unit despite being eligible for referral.
PMID- 28420572
TI - Nutritional management of cystic fibrosis - an update for the 21st century.
AB - Nutritional management is an essential part of multidisciplinary care for
infants, children and adults with cystic fibrosis (CF). In 2016 two updated
nutritional consensus guidelines were published [1,2]. This review will explore
some of the key points in the nutritional management of people with CF in the
21st Century.
PMID- 28420573
TI - Low levels of physical activity in Sudanese individuals with some features of
metabolic syndrome: Population based study.
AB - BACKGROUND: The aim of this study was to evaluate the level of physical activity
among Sudanese population. METHODS: A descriptive cross sectional study composed
of 323 participants from Khartoum state, Sudan. Data collected using pretested
designed questionnaire based on previously validated Global Physical Activity
Questionnaire. The demographic and physical measurement including blood glucose,
anthropometric and blood pressure. RESULTS: The Mean age of participants was
35.5. Males were 59.9% and females 47.1% and the prevalence of inactivity was
53.8%. Despite the fact that males are more active than females (P<0.000)
physical activity tends to decrease with age but this not statistically
significant. Physical activity is significantly decreased with obesity, higher
education and doing sedentary jobs (P<0.018, P<0.000 and P<0.000 respectively).
While majority of individuals with hypertension and pre-hypertension tend to do
less physical activity (P<0.045 and P<0.008 respectively). Logistic regression
analysis shown that gender is absolute risk factor for physical activity. Males
have more than three times probability of being physically active than women
OR3.82 (1.91-7.30). In this study, physical activity was not affected by central
obesity (P<0.497), diabetes (P<0.378) and being married or not (P<0.135).
CONCLUSION: Physical activity in Sudanese women was significantly decreased in
comparison with men.
PMID- 28420574
TI - Vitamin supplements in type 2 diabetes mellitus management: A review.
AB - Type 2 diabetes mellitus (T2DM) is a major public health challenge that affects
countries across the world. The use of pharmacological therapy is often limited
in some patients due to a loss of effect over time or development of adverse
effects such as weight gain or hypoglycaemia. This has prompted searches into the
role of non-pharmacological therapies in T2DM. The availability and use of
vitamin supplements in developed countries have increased significantly and there
is evidence that certain vitamins may have roles in the management of T2DM. This
review examines the literature assessing the use of vitamins A, C, E, D, K and
the B group vitamins (B1, B3, B7, B6, B9, B12) in the management of T2DM. No
clear evidence supporting the beneficial role of any specific vitamin in the
treatment of T2DM was found. Thus, it is recommended that until further studies
are conducted to clarify the role of such vitamins in T2DM management, they
should not be routinely recommended in clinical practice.
PMID- 28420575
TI - Correlation of various serum biomarkers with the severity of diabetic
retinopathy.
AB - : Hyperglycemia induced inflammation and angiogenic factors are implicated as a
contributor to the onset and progression of diabetic retinopathy (DR) in type 2
diabetes mellitus patients (T2DM). Tumor necrosis factor (TNF-alpha) and C
reactive protein (CRP) are inflammatory cytokines which induce retinal VEGF and
are involved in the progression of proliferative diabetic retinopathy (PDR).
Therefore the aim of the present study is to investigate the relationship between
diabetic retinopathy and systemic inflammation in patients with type 2 diabetes
mellitus. MATERIALS AND METHODS: Patients with T2DM, with or without diabetic
retinopathy were included in the study. Serum inflammatory cytokines, vascular
growth factor were studied in different stages of DR. RESULTS: Patients with T2DM
with and without diabetic retinopathy were compared. Patients with diabetic
retinopathy had increased serum levels of inflammatory cytokines CRP, TNF-alpha,
as well as VEGF compared to serum levels of diabetic patients without
retinopathy. CONCLUSION: T2DM patients with retinopathy have higher levels of
circulating inflammatory cytokines and VEGF compared to patients without
retinopathy. These proinflammatory cytokines and angiogenic factors are involved
in the progression of DR and proliferative diabetic retinopathy. The results
showed the importance of inflammation and vascular endothelial growth factor in
the progression of NPDR and PDR.
PMID- 28420576
TI - Prevalence of hypertension and prehypertension in adolescence in Ahvaz, Iran.
AB - BACKGROUND: High blood pressure is a risk factor for some disease like stroke,
coronary heart disease, and renal failure. High blood pressure in children is an
increasing health problem. OBJECTIVES: The aim of this study was to determine
prevalence of hypertension and pre-hypertension age between 10 to 17 years old.
PATIENTS AND METHODS: This descriptive analytic study was conducted using
multiphase sampling method in Ahvaz (Southwest of Iran). A questionnaire include:
height, weight, and body mass index, systolic and diastolic blood pressures
filled for each participant. Blood pressure was measured twice for each person.
For the diagnosis of hypertension, the fourth report of the Diagnosis,
Evaluation, and Treatment of High Blood Pressure in Children and Adolescents of
the National Health Institute of United States was used. RESULTS: Total
participants of the study were 1707children and adolescents including 922 boys
(54%) and 785 girls (46%). The prevalence of high blood pressure was 1.7% (2.5%
in boys and 0.8%). The prevalence of pre-hypertension was 9%(7.6% in boys, 10.6%
in girls). The mean systolic and diastolic blood pressures increased with
increasing body mass index. CONCLUSIONS: The prevalence of high blood pressure
was found to be lower than other studies in our country. The prevalence of the
high blood pressure in boys was significantly higher than girls. This study, like
other studies showed high correlation between being overweight and an increase in
systolic and diastolic blood pressure.
PMID- 28420577
TI - Effect of short-term yoga-based lifestyle intervention on plasma glucose levels
in individuals with diabetes and pre-diabetes in the community.
AB - AIM: To study the effect of short term Yoga-based lifestyle intervention in the
management of diabetes and pre-diabetes, through a 'pilot' community-based study.
METHODS: A total of 1292 subjects with diagnosed type 2 diabetes and pre-diabetes
were recruited from different States of India viz., Karnataka, Maharashtra,
Gujarat, Rajasthan, and Tamilnadu participated in the study. Yoga-based lifestyle
intervention was introduced through 10-day non-residential camps. Baseline and
post intervention assessments of fasting plasma glucose (FPG) were measured on
the first day and tenth day respectively. Of 1292 subjects, 896 both pre- and
post- FPG readings were available. Data analysis was done using statistical
package for the social sciences (SPSS), version 16. RESULTS: Mean baseline FPG
level was 133.1 (+/-47.98) and the mean post intervention FPG reduced to 121.19
(+/-40.56). There was a statistically significant decrease in FPG, p value
(<0.0001). CONCLUSION: The result suggests that a short-term Yoga-based lifestyle
intervention effectively reduces FPG levels in type 2 diabetes patients and pre
diabetes.
PMID- 28420578
TI - Metabolic syndrome and its components are related to psychological disorders: A
population based study.
AB - BACKGROUND: Psychological disorders are considered as today's one of the most
important public health problems all around the world. Another alarming
condition, which attributed to cardiovascular disease (CVD) is metabolic syndrome
(Mets). The aims of the current study were to explore (1) the prevalence of
anxiety and depression in a large representative population of Iran, and (2)
evaluate their possible association with MetS patients. METHOD: Applying a
randomized stratified-cluster approach, 9829 adults, aged 35-65 years, were
recruited as part of the MASHAD study. Socio demographic, anthropometric and
biochemical analyses were performed. Beck's anxiety inventory and Beck's
depression inventory II were applied to assessment of the degree of anxiety and
depression among the subjects. RESULTS: The prevalence of MetS, anxiety and
depression were 38.8%, 25% and 31.5%, respectively. The prevalence of these
factors was significantly (P<0.05) higher in women, compared to men and subjects
with MetS were significantly (P<0.05) associated with both anxiety and
depression. Additionally, multivariate analysis after adjusting for potential
confounders showed a significant relationship between MetS and anxiety (p=0.04).
CONCLUSION: Our data demonstrates the significant association of MetS components
with anxiety and depression and high prevalence of these co-morbidities in
adults, particularly in women.
PMID- 28420579
TI - Clustering of cardio metabolic risk factors in Iranian adult population: A
growing problem in the north of Iran.
AB - INTRODUCTION: The clustering of components of metabolic syndrome (MetS) is a
major concern in a transition population because of dramatic changing toward
modern life styles. The objective of this study was to determine the prevalence
of clustering of various combinations of MetS and its association with obesity.
METHODS AND SUBJECTS: In a population- based cross-sectional study, a
representative samples of 1000 adults were recruited in Babol, the north of Iran.
The demographic data, blood pressure, body mass index and waist circumference
(WC) were measured with standard method. Fasting blood sugar, serum levels of
triglycerides, high density lipoprotein were measured with enzymatic method.
RESULTS: A quarter of population had only one component of MetS. The prevalence
of just two components was 30.7% and 26.2% in men and women respectively and
about 67.1% of men and 73.3% of women had >=2 risk factors (P=0.001). While the
joint prevalence of three and four components was 22.0% and 12.0% in male and
27.3% and 16.5% in female respectively. The combination of high WC with any of
other four components of MetS were significantly higher compared with any other
joint combinations in particularly among women (P=0.001). The adjusted odds ratio
for having clustering (>=2 risk factors) increased 5.6 times (95%CI: 2.15, 6.04)
in obese subjects and remained at significant level after adjustment for age,
sex, level of education. CONCLUSION: An emerging high rate of clustering of joint
combination of cardio metabolic risk factors highlights an urgent intervention
for life style modification in public health management.
PMID- 28420580
TI - Comparative pharmacodynamic analysis of imidazoline compounds using rat model of
ocular mydriasis with a test of quantitative structure-activity relationships.
AB - Imidazol(in)e derivatives, having the chemical structure similar to clonidine,
exert diverse pharmacological activities connected with their interactions with
alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as
antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic
effects. The mechanism of pupillary dilation observed after systemic
administration of imidazol(in)es to rats, mice and cats depends on the
stimulation of postsynaptic alpha2-adrenoceptors within the brain. It was proved
that the central nervous system (CNS)-localized I1-imidazoline receptors are not
engaged in those effects. It appeared interesting to analyze the CNS-mediated
pharmacodynamics of imidazole(in)e agents in terms of their chromatographic and
calculation chemistry-derived parameters. In the present study a systematic
determination and comparative pharmacometric analysis of mydriatic effects in
rats were performed on a series of 20 imidazol(in)e agents, composed of the well
known drugs and of the substances used in experimental pharmacology. The eye
pupil dilatory activities of the compounds were assessed in anesthetized Wistar
rats according to the established Koss method. Among twenty imidazol(in)e
derivatives studied, 18 produced diverse dose-dependent mydriatic effects. In the
quantitative structure-activity relationships (QSAR) analysis, the
pharmacological data (half maximum mydriatic effect - ED50 in MUmol/kg) were
considered along with the structural parameters of the agents from molecular
modeling. The theoretically calculated lipophilicity parameters, CLOGP, of
imidazol(in)es, as well as their lipophilicity parameters from HPLC, logkw, were
also considered. The attempts to derive statistically significant QSAR equations
for a full series of the agents under study were unsuccessful. However, for a
subgroup of eight apparently structurally related imidazol(in)es a significant
relationship between log(1/ED50) and logkw values was obtained. The lack of
"predictive" QSAR for the whole series of the structurally diverse agents is
probably due to a complex mechanism of the ligand-alpha2-adrenergic receptor
interactions, which are predominantly of a highly structurally specific polar
nature. Such interactions are difficult to quantify with the established chemical
structural descriptors, contrary to the less specific, molecular bulkiness
related interactions.
PMID- 28420582
TI - Are current flow models for transcranial electrical stimulation fit for purpose?
PMID- 28420581
TI - Response variability of different anodal transcranial direct current stimulation
intensities across multiple sessions.
AB - BACKGROUND: It is well known that transcranial direct current stimulation (tDCS)
is capable of modulating corticomotor excitability. However, a source of growing
concern has been the observed inter- and intra-individual variability of tDCS
responses. Recent studies have assessed whether individuals respond in a
predictable manner across repeated sessions of anodal tDCS (atDCS). The findings
of these investigations have been inconsistent, and their methods have some
limitations (i.e. lack of sham condition or testing only one tDCS intensity).
OBJECTIVE: To study inter- and intra-individual variability of atDCS effects at
two different intensities on primary motor cortex (M1) excitability. METHODS:
Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in
three separate conditions (2 mA, 1 mA, sham) each repeated three times separated
by 48 h. Motor evoked potentials were recorded before and after stimulation (up
to 30min). Time of testing was maintained consistent within participants. To
estimate the reliability of tDCS effects across sessions, we calculated the Intra
class Correlation Coefficient (ICC). RESULTS: AtDCS at 2 mA, but not 1 mA,
significantly increased cortical excitability at the group level in all sessions.
The overall ICC revealed fair to high reliability of tDCS effects for multiple
sessions. Given that the distribution of responses showed important variability
in the sham condition, we established a Sham Variability-Based Threshold to
classify responses and to track individual changes across sessions. Using this
threshold an intra-individual consistent response pattern was then observed only
for the 2 mA condition. CONCLUSION: 2 mA anodal tDCS results in consistent intra-
and inter-individual increases of M1 excitability.
PMID- 28420583
TI - Diabetes medication persistence, different medications have different persistence
rates.
AB - AIM: To assess the persistence of diabetic patients to oral medications. METHODS:
The study included all type 2 diabetic patients over 40 years, members of one
District of Clalit Health Services Israel, who were diagnosed with diabetes
mellitus before 2008 and who filled at least one prescription per year during
2008-2010, for the following medications: metformin, glibenclamide, acarbose,
statins, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II
receptor antagonists (ARBs). Purchase of at least 9 monthly prescriptions during
2009 was considered "good medication persistence". We compared HbA1c and LDL
levels, according to medication persistence, for each medication; and cross
persistence rates between medications. RESULTS: 21,357 patients were included.
Average age was 67.0+/-11.0years, 48.9% were men, and 35.8% were from low SES.
Good medication persistence rates for ARBs were 78.8%, ACEI 69.0%, statins 66.6%,
acarbose 67.8%, metformin 58.6%, and glibenclamide 55.3%. Good persistence to any
of the medications tested was associated with a higher rate of good persistence
to other medications. Patients who took more medications had better persistence
rates. CONCLUSIONS: Different oral medications used by diabetic patients have
different persistence rates. Good persistence for any one medication is an
indicator of good persistence to other medications. Investment in enhancing
medication persistence in persons with diabetes may improve persistence to other
medications, as well as improve glycemic control.
PMID- 28420584
TI - Neuroendocrine Carcinoma of the Breast With Endobronchial Metastases and Syndrome
of Inappropriate Antidiuretic Hormone Secretion.
PMID- 28420585
TI - Adjuvant Chemotherapy Is Associated With Improved Overall Survival in Locally
Advanced Rectal Cancer After Achievement of a Pathologic Complete Response to
Chemoradiation.
AB - BACKGROUND: In locally advanced rectal adenocarcinoma, 15% to 20% of patients
treated with neoadjuvant chemoradiation (nCRT) achieve a pathologic complete
response (pCR). The benefit of adjuvant chemotherapy is controversial in rectal
cancer. Our objective was to evaluate the effect of clinical risk factors and
adjuvant chemotherapy usage on the outcomes of the pCR patient population.
PATIENTS AND METHODS: We performed a retrospective study using the National
Cancer Data Base from 2006 to 2013. The primary outcome was overall survival
(OS). The association between OS and patient characteristics (demographics, tumor
variables, and treatment) was examined using multivariable Cox regression
modelling. RESULTS: A total of 2891 patients were identified who had achieved a
pCR. Of these 2891 patients, 2102 received nCRT and 789 received nCRT followed by
adjuvant chemotherapy. The median follow-up duration was 43.2 months. The factors
significantly associated with OS included age (P < .001), gender (P = .011),
Charlson-Deyo comorbidity score (P < .001), grade (P = .029), clinical T stage (P
= .030), carcinoembryonic antigen negativity (P = .002), and receipt of adjuvant
chemotherapy (P < .001). Nodal status was not significantly associated with
survival. The 5-year OS rate was 94% in the nCRT plus adjuvant group compared
with 84% in the nCRT-alone group. Adjuvant chemotherapy was more likely to be
given to younger patients (aged < 60 years), higher grade, lower Charlson-Deyo
comorbidity score, elevated carcinoembryonic antigen level, higher clinical T
stage, and higher clinical N stage. CONCLUSION: Our findings showed a significant
improvement in OS for patients who received nCRT plus adjuvant chemotherapy
compared with those who received nCRT alone. The nCRT plus adjuvant patients were
more likely to be younger, have a lower comorbidity score, have clinical >= T3
disease, and have clinical node-positive disease. Thus, a selection bias could
have been present. Nonetheless, even in the setting of already excellent
outcomes, for patients with locally advanced rectal adenocarcinoma who achieve a
pCR, the additional benefit of adjuvant chemotherapy should be weighed against
the potential for toxicity.
PMID- 28420586
TI - Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass.
AB - The anatomic and physiologic changes in the gastrointestinal (GI) tract after
bariatric surgery may significantly affect the pharmacokinetics of medications
taken by the patients for various reasons. Unfortunately, there is little
information regarding changes in drug absorption after bariatric surgeries,
limiting the ability of medical professionals to produce clear recommendations on
what changes should be made to the formulations and dosing regimens of drugs
after bariatric surgery. In this article, we report and analyze a case of 52-year
old male patient with morbid obesity and attention-deficit/hyperactivity disorder
(ADHD) who experienced lack of methylphenidate efficacy after Roux en-Y gastric
bypass (RYGB), which was eventually resolved by using the transdermal patch
instead of an oral product. Interestingly, in the same patient, a prior gastric
band had no effect on the drug's efficacy. Especially in light of a recent case
report of methylphenidate toxicity after RYGB, these 2 cases suggest that
bariatric surgeries may alter the absorption of orally administered
methylphenidate in an unpredictable manner; hence, it is prudent to closely
monitor the therapeutic/toxic effects of methylphenidate after bariatric surgery,
and to be aware of nonoral treatment options of this medication.
PMID- 28420587
TI - Should recent smoking be a contraindication for sleeve gastrectomy?
AB - BACKGROUND: One of the ultimate goals of bariatric and metabolic surgery is to
decrease cardiovascular morbidity and mortality. Obese individuals who smoke
tobacco are at an increased risk of cardiovascular events and may benefit the
most by positive effects of bariatric surgery on cardiometabolic risk factors.
The safety profile of sleeve gastrectomy in patients who smoke has not yet been
characterized. OBJECTIVES: To investigate the independent effect of smoking on
early postoperative morbidity and mortality of laparoscopic sleeve gastrectomy.
SETTING: American College of Surgeons National Surgical Quality Improvement
Program (NSQIP) database. METHODS: All patients undergoing primary laparoscopic
sleeve gastrectomy from 2010 to 2014 were identified within the NSQIP database.
Thirty-day postoperative outcomes for smokers, defined as patients who smoked
within the year before surgery, were compared with nonsmokers. RESULTS: A total
of 33,714 people underwent sleeve gastrectomy; 30,418 (90.2%) patients were
nonsmokers, whereas 3296 (9.8%) patients smoked within a year before surgery.
Among the 17 examined individual adverse events, patients who smoked were more
likely to experience an unplanned reintubation (odds ratio [OR] = 1.88, 95%
confidence interval [CI]: 1.01-3.50). Patients in the smoking group were
significantly more likely to experience a composite morbidity event (4.3% versus
3.7%, P = .04), serious morbidity event (.9% versus .6%, P = .003), and 30-day
mortality (0.2% versus .1%, P = .0004). The length of hospital stay, unplanned
readmission, and readmission rates were comparable between the 2 groups. These
differences in the composite morbidity event, serious morbidity event, and
mortality persisted even when those patients with chronic obstructive pulmonary
disease, used as a surrogate for end-stage pulmonary effects of smoking, were
excluded from the analysis. CONCLUSION: Sleeve gastrectomy is a well-tolerated
procedure in nonsmokers and smokers. However, patients who have smoked within a
year before sleeve gastrectomy are at an increased, albeit still very low, risk
for 30-day morbidity and mortality compared with nonsmokers. Additional studies
are needed to determine if long-term improvement in co-morbidities can offset
this initial modest increased perioperative risk.
PMID- 28420588
TI - Comparison of an electronic versus traditional food diary for assessing dietary
intake-A validation study.
AB - BACKGROUND: Paper-based estimated food diaries are often used in research to
collect dietary data, despite this method being burdensome for both participants
and researchers. Such food diaries are often time consuming, labour intensive,
and rely on participant literacy and therefore may lead to greater rates of under
reporting. METHODS: This study assessed the validity of the 'Boden Food Plate', a
novel web-based electronic application, compared to a paper-based three-day
estimated food diary. Participants were also asked to rate their satisfaction
with the new electronic diary. Sixty-seven participants with overweight or
obesity completed both the electronic and paper-based diaries at two different
time-points. RESULTS: Baseline BMI of participants (mean+/-standard deviation
(SD)) was 30.4+/-2.9kg/m2, body weight was 87.6+/-13.4kg, and age was 42.3+/
7.7years. Fifty four percent (n=41) of the cohort were female. Bland Altman plots
for total energy, and percentage of total energy intake from fat, carbohydrate,
and protein, indicated wide limits of agreement between the two methods of
dietary data collection, and in some analyses there were a few cases that did not
lie within the 95% confidence intervals. Approximately 70% of participants rated
the electronic food diary as easier to use and more fun when compared to the
traditional paper-based estimated food diary. CONCLUSION: Innovative and visual
dietary collection applications such as the 'Boden Food Plate' provide an
enjoyable and interactive means of measuring nutritional intake in a time
efficient manner. Further validation studies incorporating micronutrient analysis
and to improve the applications validity are warranted.
PMID- 28420589
TI - Associations between language acculturation, age of immigration, and obesity in
the Mexican American Mano A Mano cohort.
AB - INTRODUCTION: As Mexican immigrants to the U.S. become acculturated, they face
worsening health outcomes such as obesity. The role of language acculturation in
the development of obesity has not been thoroughly examined. METHODS: To examine
associations between language acculturation and obesity, data were drawn from the
Mexican-American Mano A Mano cohort study. Participants aged 20 years and over
(n=18,298) completed baseline questionnaires on socio-demographic and behavioural
factors, including physical activity and sitting time. The Bi-dimensional
Acculturation Scale for Hispanics assessed language acculturation. Multivariate
adjusted logistic regression was conducted to investigate associations between
language acculturation, immigration age, and obesity, and whether sitting time
and physical activity mediated these associations. RESULTS: Individuals with
obesity were more linguistically acculturated than individuals who were normal
weight or overweight (P<0.001); however, this relationship differed by gender and
nativity. Among Mexico-born women, language acculturation score was inversely
related to BMI (P<0.001). Language acculturation was associated with higher risk
of obesity (OR=1.35, 95% CI: 1.12-1.62) in U.S.-born participants and lower risk
in Mexico-born participants (OR=0.90, 95%CI=0.81-1.00). For Mexico-born
participants, arrival in the U.S. as an adult (>=20years old) was associated with
a reduced obesity risk (OR=0.74, 95% CI: 0.67-0.80). Sitting time mediated the
association between language acculturation and obesity. CONCLUSIONS: Language
acculturation may influence obesity development among the U.S.-born Mexican
Americans in this cohort, but not their Mexico-born counterparts. Sitting time
could be targeted in obesity prevention efforts in this population.
PMID- 28420590
TI - Volume and dimensions of angiographically normal coronary arteries assessed by
multidetector computed tomography.
AB - BACKGROUND: The objective of this study was to determine normal values for
coronary artery volume (CAV) and individual vasculature and segment dimensions.
METHODS: We examined 200 healthy volunteers with an Agatston score of 0 and a
normal, high quality coronary CTA. Using 320 slice multidetector row CT and
designated vessel tracing software with border detection algorithm, the main
coronary arteries and branches were delineated and total and segmental dimensions
calculated. RESULTS: 2931 segments (98.9%) could be adequately delineated. Of the
173 subjects with adequate coronary delineations, 140 subjects (81%) received
nitroglycerin (NTG) prior to the scan. CAV was 4.33 ml (95% CI: 2.27-6.39) in
subjects with NTG and 2.55 ml (95% CI: 0.34-4.76) in subjects without NTG (p <
0.0001). Left ventricular mass (LVM) was strongly correlated with CAV (p <
0.0001) independently of body surface area and gender, whereas gender was not
independently correlated with CAV. From right, balanced to left coronary
dominance, the left anterior descending artery vasculature mean contribution to
CAV increased slightly (37%, 40% and 43%, p = 0.002), and the mean contributions
of right coronary artery (RCA) and left circumflex artery (LCX) vasculature was
inversely related - from right, balanced to left 46%, 32% and 16% for RCA (p <
0.0001); and 16%, 27% and 38% for LCX (p < 0.0001). CONCLUSION: Normal values for
coronary artery volume as assessed by coronary CTA are reported. They strongly
correlate with NTG administration and left ventricular mass. The respective
contribution of the left and right coronary vascularture is influenced by
coronary dominance.
PMID- 28420591
TI - SCCT and CTA - The future is now.
PMID- 28420592
TI - Association between perceived discrimination and healthcare-seeking behavior in
people with a disability.
AB - BACKGROUND: Experiences of discrimination lead people from vulnerable groups to
avoid medical healthcare. It is yet to be known if such experiences affect people
with disabilities (PWD) in the same manner. OBJECTIVES: To determine the
association between perceived discrimination and healthcare-seeking behavior in
people with disabilities and to explore differences of this association across
disability types. METHODS: We performed a cross-sectional study with data from a
national survey of people with disabilities. Perceived discrimination and care
seeking behavior were measured as self-reports from the survey. Dependence for
daily life activities, possession of health insurance, and other disability
related variables were included and considered as confounders. We used Poisson
regression models and techniques for multistage sampling in the analyses. A
stratified analysis was used to explore effects of discrimination across types of
disability. RESULTS: Most of PWD were 65 years or older (67.1%). Prevalence of
healthcare seeking was 78.8% in those who perceived discrimination, and 86.1% in
those who did not. After adjusting for potential confounders, the probability of
not seeking care was higher in people who reported perceived discrimination
(adjusted PR = 1.15; 95%CI: 1.04-1.28). In a stratified analysis, significant
effects of discrimination were found in people with communication disability
(adjusted PR = 1.34, 95%CI: 1.07-1.67) and with physical disability (adjusted PR
= 1.17, 95%CI: 1.03-1.34). CONCLUSIONS: People with disabilities who perceive
discrimination are less likely to seek healthcare. This association was higher
for people with communication and physical disabilities. These results provide
evidence to institutions who attempt to tackle discrimination.
PMID- 28420593
TI - Sexual health in the community: Services for people with intellectual and
developmental disabilities.
AB - BACKGROUND: Sexuality is a central dimension of overall health and well-being.
People with intellectual and developmental disabilities (IDD) continue to
experience disparities in healthcare, particularly regarding access to sexual
health related services. Medicaid Home and Community-Based Services (HCBS)
waivers are ideally situated to provide sexual and reproductive healthcare in
accessible settings. OBJECTIVE: This preliminary study analyzed national Medicaid
HCBS waivers to determine how they provide sexuality services for people with
IDD. METHODS: 111 FY 2015 HCBS 1915(c) waivers for people with IDD from 46 states
and the District of Columbia were analyzed to determine which waivers were
providing services related to sexuality. Expenditure and utilization data were
analyzed to determine service allotment. RESULTS: Currently, less than 12% of
waivers include any kind of sexuality services, and those services provided are
predominantly reactive, rather than proactive. Reactive services focused on
interrupting sexually inappropriate behaviors through assessments and plans,
intervention and therapy, and supervision. Meanwhile, proactive services promoted
the healthy sexuality of people with IDD by providing sexuality education related
to sexuality awareness, reproduction, and victimization avoidance. CONCLUSIONS:
The limited availability of Medicaid HCBS sexuality service provision not only
hints at a lack of understanding of sexuality for people with IDD, but also
presents an opportunity to perform increased evaluations on current service
offerings in order to justify future expanded offerings in other states.
PMID- 28420594
TI - Population data of 18 autosomal STR loci in the Chinese Han population from
Heilongjiang Province, Northeast China.
PMID- 28420595
TI - Using an array of implementation strategies to improve success rates of
pharmacist-initiated medication therapy management services in community
pharmacies.
AB - BACKGROUND: With the introduction of the Centers for Medicare and Medicaid
Services Stars Measure program has come a greater expectation of Medication
Therapy Management (MTM) services from community pharmacies. To meet the growing
demand of these services, pharmacies have sought out various methods of engaging
pharmacists to provide MTM. Barriers for completing MTM include inadequate time
to complete the services, insufficient staffing, lack of sufficient compensation,
billing difficulty, lack of interest among patients (including refusing MTM
services when offered), inadequate training/experience, and lack of support from
management. OBJECTIVE: To evaluate the impact of a financial incentive alone
versus the incentive plus a package of individualized implementation strategies
on the success rate of MTM services. METHODS: To increase MTM completion rates,
The Kroger Company implemented a financial incentive for pharmacists in one of
its market services areas. The following year the incentive was continued and an
array of training and support strategies were implemented. The numbers of MTM
claims and success rates for 2013 (no intervention), 2014 (financial incentive
alone), and 2015 (incentive plus required training and ongoing support) were
compared. RESULTS: A total of 7038 claims were extracted from 2013 to 2015. The
number of completed claims had increased from 1385 in 2013 to 3265 in 2015. The
total MTM success rates rose significantly from 42.9% in 2013 to 49.0% in 2014 (p
= 0.001) and to 64.0% in 2015 (p < 0.001). CONCLUSIONS: A financial incentive
plus a package of individualized implementation strategies increases success
rates of MTM services compared to a financial incentive alone.
PMID- 28420596
TI - The behaviors and experiences of the community pharmacy team on the provision of
multi-compartment compliance aids.
AB - BACKGROUND: Multi-compartment compliance aids (MCAs) are repackaging systems for
solid dosage form medicines. Acknowledging the lack of evidence that MCAs improve
adherence or clinical outcomes, the Royal Pharmaceutical Society has expressed
concern that MCAs have 'become regarded as a panacea for medicines use'.
OBJECTIVES: To determine the behaviors and experiences of the community pharmacy
team around MCA provision. METHODS: A cross-sectional survey was conducted in 26
community pharmacies in the north east of Scotland. Survey items were grouped
into: current activities in the provision of MCAs; potential influences on these
activities; reports of patient experiences; and demographics. Data were analysed
using descriptive and inferential statistics, and content analysis of responses
to open questions. Principal component analysis (PCA) was performed on the items
of potential influences on activities. RESULTS: Data were collected from 136
community team members (median 4, range1-10 per pharmacy; 32.3% pharmacists). All
were involved in some aspect of MCA provision and within the same pharmacy,
several different staff positions were commonly involved in the same activity.
PCA gave seven components; the lowest scores were obtained for the component of
'others expecting me to provide MCAs'. Participants agreed that GPs, patients and
their families, and carers expected them to provide MCAs. Positive experiences of
MCA provision were in themes of promoting patient adherence, reducing patient
stress and enhancing patient monitoring. Further negative experiences were in of
lack of shared patient decision making, worsening adherence and generation of
medicines waste, and dealing with changing medicines. MCAs were not always
considered to be the most appropriate solution. CONCLUSION: While community
pharmacy teams value MCAs, there may be issues around staff assignment to
particular roles, expectations from others and reports of negative patient
experiences. A systematic approach to MCA provision and monitoring involving the
multidisciplinary health and social care team is warranted.
PMID- 28420597
TI - Discrepant lesion size estimated on T1- and fat-suppressed T2-weighted MRI:
diagnostic value for differentiation between inflammatory pseudotumor and
carcinoma of the nasopharynx.
AB - PURPOSE: Nasopharyngeal inflammatory pseudotumor (NIPT) is hard to differentiate
from infiltrating nasopharyngeal carcinoma (NPC) on conventional magnetic
resonance imaging (MRI). The purpose of this study is to determine whether
discrepant lesion sizes estimated on T1- and fat-suppressed T2-weighted images
can help distinguish between NIPT and NPC. METHODS: We retrospectively reviewed
MRI data of histologically proven 14 NIPTs and 18 infiltrating NPCs. We measured
the area of the lesion on contrast-enhanced T1-weighted, unenhanced T1-weighted,
and fat-suppressed T2-weighted images by placing the largest possible polygonal
region-of-interest within the lesion at the same level. Using lesion size
measured on contrast-enhanced T1-weighted image as the reference, we calculated
and compared area ratio of T1 (ART1) and area ratio of T2 (ART2) between NIPTs
and NPCs. For validation, we also undertook a double-blinded study by two
reviewers and assessed the diagnostic performance and interobserver agreement.
RESULTS: For NIPTs, ART2 (median, 0.48; range, 0.18-0.97) was statistically
significantly less than ART1 (median, 1.01; range, 0.80-1.99), while these values
were not significantly different for NPCs. The interobserver agreement in
differentiating between NIPT and NPC was good, with a sensitivity of 93% and a
specificity of 83%-94%. CONCLUSION: In contrast to NPCs, NIPTs appear smaller on
fat-suppressed T2-weighted images than on T1-weighted images. This discrepancy in
the lesion size estimated on T1-weighted and fat-suppressed T2-weighted images
may provide a simple and consistent way to differentiate between NIPTs and NPCs
on conventional MRI.
PMID- 28420598
TI - 1.5 T augmented reality navigated interventional MRI: paravertebral sympathetic
plexus injections.
AB - PURPOSE: The high contrast resolution and absent ionizing radiation of
interventional magnetic resonance imaging (MRI) can be advantageous for
paravertebral sympathetic nerve plexus injections. We assessed the feasibility
and technical performance of MRI-guided paravertebral sympathetic injections
utilizing augmented reality navigation and 1.5 T MRI scanner. METHODS: A total of
23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%), and
hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively
planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented
reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA
enhanced saline was injected. Outcome variables included the number of control
magnetic resonance images, target error of the needle tip, punctures of critical
nontarget structures, distribution of the injected fluid, and procedure length.
RESULTS: Augmented-reality navigated MRI guidance at 1.5 T provided detailed
anatomical visualization for successful targeting of the paravertebral space,
needle placement, and perineural paravertebral injections in 46 of 46 targets
(100%). A mean of 2 images (range, 1-5 images) were required to control needle
placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and
changes of needle advancement occurred in 6 of 46 targets (13%), which were
statistically not related to spinal regions (P = 0.728 and P = 0.86,
respectively) and cadaver sizes (P = 0.893 and P = 0.859, respectively). The mean
error of the needle tip was 3.9+/-1.7 mm. There were no punctures of critical
nontarget structures. The mean procedure length was 33+/-12 min. CONCLUSION: 1.5
T augmented reality-navigated interventional MRI can provide accurate imaging
guidance for perineural injections of the thoracic, lumbar, and hypogastric
sympathetic plexus.
PMID- 28420599
TI - Use of Machine Learning Classifiers and Sensor Data to Detect Neurological
Deficit in Stroke Patients.
AB - BACKGROUND: The pronator drift test (PDT), a neurological examination, is widely
used in clinics to measure motor weakness of stroke patients. OBJECTIVE: The aim
of this study was to develop a PDT tool with machine learning classifiers to
detect stroke symptoms based on quantification of proximal arm weakness using
inertial sensors and signal processing. METHODS: We extracted features of drift
and pronation from accelerometer signals of wearable devices on the inner wrists
of 16 stroke patients and 10 healthy controls. Signal processing and feature
selection approach were applied to discriminate PDT features used to classify
stroke patients. A series of machine learning techniques, namely support vector
machine (SVM), radial basis function network (RBFN), and random forest (RF), were
implemented to discriminate stroke patients from controls with leave-one-out
cross-validation. RESULTS: Signal processing by the PDT tool extracted a total of
12 PDT features from sensors. Feature selection abstracted the major attributes
from the 12 PDT features to elucidate the dominant characteristics of proximal
weakness of stroke patients using machine learning classification. Our proposed
PDT classifiers had an area under the receiver operating characteristic curve
(AUC) of .806 (SVM), .769 (RBFN), and .900 (RF) without feature selection, and
feature selection improves the AUCs to .913 (SVM), .956 (RBFN), and .975 (RF),
representing an average performance enhancement of 15.3%. CONCLUSIONS: Sensors
and machine learning methods can reliably detect stroke signs and quantify
proximal arm weakness. Our proposed solution will facilitate pervasive monitoring
of stroke patients.
PMID- 28420600
TI - Increasing Fruit and Vegetable Consumption Through a Healthy Eating Blog: A
Feasibility Study.
AB - BACKGROUND: Despite efforts made by public health organizations to improve
consumption of fruits and vegetables, populations in developed countries usually
eat less than the minimum recommended. Social media, such as blogs, represent a
unique opportunity for improving knowledge translation in health care because
they facilitate interactive communication between the public and health
professionals. However, no studies have yet evaluated the effect of blogs to
promote dietary behavior changes. OBJECTIVE: Our study aims to conduct a
preliminary assessment before undertaking a full randomized controlled trial
(RCT) of the feasibility of using an evidence-based healthy eating blog promoting
the consumption of fruits and vegetables among adult women. METHODS: A total of
80 women aged 18 years and older (mean 42, SD 13 years) eating less than five
servings per day of fruit and vegetables (mean 2.75, SD 1.84 servings) were
recruited. Participants were randomized to the healthy eating blog group (n=40),
which included a weekly blog post over a 6-month period, or to a control group
(n=40) that had no exposure to the healthy eating blog. Blog posts were written
by a registered dietitian and focused on the improvement of fruit and vegetable
consumption. We targeted four main determinants of the behavior that were
identified as the best predictors for fruit and vegetable intake by two
systematic reviews: (1) knowledge, (2) attitude, (3) self-efficacy, and (4)
motivation. The intervention was considered feasible if (1) more than 70% of
questionnaires were completed, (2) attendance rate was more than 90% for in
person appointments with the research coordinator, (3) participants accessed at
least 75% of the blog posts, and (4) the attrition rate was less than 25%. Blog
access was assessed by collecting the blog browsing history data for each
participant. RESULTS: During the intervention, 26 posts were published on the
blog. Pre- (baseline) and postintervention (6 months) questionnaires were
completed by mean 97% (SD 3%) of participants. All participants attended their in
person appointments. Women accessed mean 87% (SD 7%) of the posts published
during the intervention. Only 3% (2/80) of participants dropped out of the study.
Between the healthy eating blog and control groups, a difference of 1.0 servings
of fruits and vegetables (P<.001) indicated moderate effects of the intervention
(Cohen d=0.54). CONCLUSIONS: These results suggest that an intervention using a
healthy eating blog meets preestablished feasibility criteria. A larger-scale RCT
using the same methodology will be conducted to assess the impact of a healthy
eating blog on the dietary habits of women.
PMID- 28420601
TI - What Older People Like to Play: Genre Preferences and Acceptance of Casual Games.
AB - BACKGROUND: In recent computerized cognitive training studies, video games have
emerged as a promising tool that can benefit cognitive function and well-being.
Whereas most video game training studies have used first-person shooter (FPS)
action video games, subsequent studies found that older adults dislike this type
of game and generally prefer casual video games (CVGs), which are a subtype of
video games that are easy to learn and use simple rules and interfaces. Like
other video games, CVGs are organized into genres (eg, puzzle games) based on the
rule-directed interaction with the game. Importantly, game genre not only
influences the ease of interaction and cognitive abilities CVGs demand, but also
affects whether older adults are willing to play any particular genre. To date,
studies looking at how different CVG genres resonate with older adults are
lacking. OBJECTIVE: The aim of this study was to investigate how much older
adults enjoy different CVG genres and how favorably their CVG characteristics are
rated. METHODS: A total of 16 healthy adults aged 65 years and above playtested 7
CVGs from 4 genres: casual action, puzzle, simulation, and strategy video games.
Thereafter, they rated casual game preference and acceptance of casual game
characteristics using 4 scales from the Core Elements of the Gaming Experience
Questionnaire (CEGEQ). For this, participants rated how much they liked the game
(enjoyment), understood the rules of the game (game-play), learned to manipulate
the game (control), and make the game their own (ownership). RESULTS: Overall,
enjoyment and acceptance of casual game characteristics was high and
significantly above the midpoint of the rating scale for all CVG genres. Mixed
model analyses revealed that ratings of enjoyment and casual game characteristics
were significantly influenced by CVG genre. Participants' mean enjoyment of
casual puzzle games (mean 0.95 out of 1.00) was significantly higher than that
for casual simulation games (mean 0.75 and 0.73). For casual game
characteristics, casual puzzle and simulation games were given significantly
higher game-play ratings than casual action games. Similarly, participants'
control ratings for casual puzzle games were significantly higher than that for
casual action and simulation games. Finally, ownership was rated significantly
higher for casual puzzle and strategy games than for casual action games.
CONCLUSIONS: The findings of this study show that CVGs have characteristics that
are suitable and enjoyable for older adults. In addition, genre was found to
influence enjoyment and ratings of CVG characteristics, indicating that puzzle
games are particularly easy to understand, learn, and play, and are enjoyable.
Future studies should continue exploring the potential of CVG interventions for
older adults in improving cognitive function, everyday functioning, and well
being. We see particular potential for CVGs in people suffering from cognitive
impairment due to dementia or brain injury.
PMID- 28420602
TI - The Fitbit One Physical Activity Tracker in Men With Prostate Cancer: Validation
Study.
AB - BACKGROUND: Physical activity after cancer diagnosis improves quality of life and
may lengthen survival. However, objective data in cancer survivors are limited
and no physical activity tracker has been validated for use in this population.
OBJECTIVE: The aim of this study was to validate the Fitbit One's measures of
physical activity over 7 days in free-living men with localized prostate cancer.
METHODS: We validated the Fitbit One against the gold-standard ActiGraph GT3X+
accelerometer in 22 prostate cancer survivors under free-living conditions for 7
days. We also compared these devices with the HJ-322U Tri-axis USB Omron
pedometer and a physical activity diary. We used descriptive statistics (eg,
mean, standard deviation, median, interquartile range) and boxplots to examine
the distribution of average daily light, moderate, and vigorous physical activity
and steps measured by each device and the diary. We used Pearson and Spearman
rank correlation coefficients to compare measures of physical activity and steps
between the devices and the diary. RESULTS: On average, the men wore the devices
for 5.8 days. The mean (SD) moderate-to-vigorous physical activity (MVPA;
minutes/day) measured was 100 (48) via Fitbit, 51 (29) via ActiGraph, and 110
(78) via diary. The mean (SD) steps/day was 8724 (3535) via Fitbit, 8024 (3231)
via ActiGraph, and 6399 (3476) via pedometer. Activity measures were well
correlated between the Fitbit and ActiGraph: 0.85 for MPVA and 0.94 for steps
(all P<.001). The Fitbit's step measurements were well correlated with the
pedometer (0.67, P=.001), and the Fitbit's measure of MVPA was well correlated
with self-reported activity in the diary (0.84; P<.001). CONCLUSIONS: Among
prostate cancer survivors, the Fitbit One's activity and step measurements were
well correlated with the ActiGraph GT3X+ and Omron pedometer. However, the Fitbit
One measured two times more MVPA on average compared with the ActiGraph.
PMID- 28420603
TI - The Coags Uncomplicated App: Fulfilling Educational Gaps Around Diagnosis and
Laboratory Testing of Coagulation Disorders.
AB - BACKGROUND: Patients with coagulation disorders may present to a variety of
physician specialties; however, accurate and efficient diagnosis can be
challenging for physicians not specialized in hematology, due to identified gaps
in knowledge around appropriate laboratory assays and interpretation of test
results. Coags Uncomplicated was developed to fill this unmet educational need by
increasing practical knowledge of coagulation disorders among nonexpert
physicians and other health care professionals (HCPs) in a point-of-care (POC)
setting. OBJECTIVE: The aim of this study was to assess patterns of use of the
mobile app Coags Uncomplicated, a tool designed to support education regarding
accurate and efficient diagnosis of bleeding disorders. METHODS: App metrics were
obtained by tracking registered user data. Additionally, a survey was distributed
to registered users, to assess circumstances and frequency of use. RESULTS: The
most common specialties of 7596 registered US users were hematology-oncology
(n=1534, 20.19%), hematology (n=1014, 13.35%), and emergency medicine (n=1222,
16.09%); most identified as physicians (n=4082, 53.74%). Specialties accounting
for the greatest numbers of screen views were hematology-oncology (99,390 views),
hematology (47,808 views), emergency medicine (23,121 views), and internal
medicine (22,586 views). The most common diagnostic endpoints reached were
disseminated intravascular coagulation (DIC; 2713 times), liver disease effect
(2108 times), and vitamin K deficiency (1584 times). Of 3424 users asked to take
the survey, 262 responded (7.65%); most were physicians in direct clinical care
(71%) and specialized in hematology-oncology (39%) or emergency medicine (21%).
Most frequent use was reported by hematologists (69%, >=6 times) and
hematologists-oncologists (38%, >=6 times). Most physicians (89.2%) reported
using the app for patient-case-related education around appropriate use of
laboratory tests in diagnostic evaluation. Physicians rated Lab Value Analyzer
(mean 4.43) and Lab Test Algorithm (mean 4.46) tools highly on a 5-point "how
helpful" scale and were likely to recommend the app to colleagues. CONCLUSIONS:
App use among physicians and other HCPs is consistent with value as a POC
educational tool, which may facilitate differential diagnoses and appropriate
early consultation with hematologists.
PMID- 28420604
TI - A Digital Tool to Promote Alcohol and Drug Use Screening, Brief Intervention, and
Referral to Treatment Skill Translation: A Mobile App Development and Randomized
Controlled Trial Protocol.
AB - BACKGROUND: Translation of knowledge and skills from classroom settings to
clinical practice is a major challenge in healthcare training, especially for
behavioral interventions. For example, screening, brief intervention, and
referral to treatment (SBIRT) is a highly-promoted approach to identifying and
treating individuals at risk for alcohol or drug problems, yet effective, routine
use of SBIRT has lagged. OBJECTIVE: The objective of this paper is to describe
the development, pilot testing, and trial protocol of a mobile app based on the
theory of planned behavior (TPB) to promote SBIRT skill translation and
application. METHODS: Intended for use after classroom training occurs, the
mobile app has three primary functions designed to increase behavioral intent to
deliver SBIRT: (1) review skills (ie, address knowledge and beliefs about SBIRT),
(2) apply skills with patients (ie, build confidence and perceived behavioral
control), and (3) report performance data (ie, increase accountability and social
norms and/or influence). The app includes depression and anxiety screening tools
due to high comorbidity with substance use. A randomized controlled trial (RCT)
is in progress among health and social service learners (N=200) recruited from 3
universities and 6 different training programs in nursing, social work, internal
medicine, psychiatry, and psychology. Participants are randomized to SBIRT
classroom instruction alone or classroom instruction plus app access prior to
beginning their field placement rotations. TPB-based data are collected via
Qualtrics or via the mobile app pre-post and SBIRT utilization, weekly for 10
weeks. Key outcomes include the frequency of and self-reported confidence in
delivery of SBIRT. RESULTS: Beta testing with advanced practice nursing students
(N=22) indicated that the app and its associated assessment tools were acceptable
and useful. The system usability scale (SUS) mean was 65.8 (n=19), which
indicated that the SBIRT app was acceptable but could benefit from improvement.
Indeed, modifications were implemented prior to starting the trial. Enrollment of
trial participants began in September 2016. Results are expected by December
2017. CONCLUSIONS: This report describes the process of TPB-based app development
and testing, and the protocol for a RCT to determine the effectiveness of the app
in enhancing skill translation. If effective, this approach could improve SBIRT
implementation, fidelity, and clinical outcomes.
PMID- 28420605
TI - Scalable Passive Sleep Monitoring Using Mobile Phones: Opportunities and
Obstacles.
AB - BACKGROUND: Sleep is a critical aspect of people's well-being and as such
assessing sleep is an important indicator of a person's health. Traditional
methods of sleep assessment are either time- and resource-intensive or suffer
from self-reporting biases. Recently, researchers have started to use mobile
phones to passively assess sleep in individuals' daily lives. However, this work
remains in its early stages, having only examined relatively small and
homogeneous populations in carefully controlled contexts. Thus, it remains an
open question as to how well mobile device-based sleep monitoring generalizes to
larger populations in typical use cases. OBJECTIVE: The aim of this study was to
assess the ability of machine learning algorithms to detect the sleep start and
end times for the main sleep period in a 24-h cycle using mobile devices in a
diverse sample. METHODS: We collected mobile phone sensor data as well as daily
self-reported sleep start and end times from 208 individuals (171 females; 37
males), diverse in age (18-66 years; mean 39.3), education, and employment
status, across the United States over 6 weeks. Sensor data consisted of
geographic location, motion, light, sound, and in-phone activities. No specific
instructions were given to the participants regarding phone placement. We used
random forest classifiers to develop both personalized and global predictors of
sleep state from the phone sensor data. RESULTS: Using all available sensor
features, the average accuracy of classifying whether a 10-min segment was
reported as sleep was 88.8%. This is somewhat better than using the time of day
alone, which gives an average accuracy of 86.9%. The accuracy of the model
considerably varied across the participants, ranging from 65.1% to 97.3%. We
found that low accuracy in some participants was due to two main factors: missing
sensor data and misreports. After correcting for these, the average accuracy
increased to 91.8%, corresponding to an average median absolute deviation (MAD)
of 38 min for sleep start time detection and 36 min for sleep end time. These
numbers are close to the range reported by previous research in more controlled
situations. CONCLUSIONS: We find that mobile phones provide adequate sleep
monitoring in typical use cases, and that our methods generalize well to a
broader population than has previously been studied. However, we also observe
several types of data artifacts when collecting data in uncontrolled settings.
Some of these can be resolved through corrections, but others likely impose a
ceiling on the accuracy of sleep prediction for certain subjects. Future research
will need to focus more on the understanding of people's behavior in their
natural settings in order to develop sleep monitoring tools that work reliably in
all cases for all people.
PMID- 28420606
TI - Epigenetic regulation and related diseases during placental development.
AB - The placenta is vital to fetal growth and development, as it bridges the fetus
and the mother. Genome-wide epigenetic regulations (e.g., DNA methylation,
histone modifications, non-coding RNAs) participate in many aspects of placenta
development, including decidua of the uterus, trophoblast cell adhesion and
invasion, angiogenesis and placental imprinted gene expression. Environmental
factors during pregnancy, such as heavy metals, chemical compounds, modern
assisted reproductive technology and the nutrient conditions, may cause abnormal
placental epigenetics. Furthermore, sex differential expression of placental
genes also contributes to epigenetic modifications. As prenatal DNA methylation
analysis can detect abnormal epigenetic modifications, it is a potential
diagnosis tool for early stage diseases and may help disease intervention and
treatment. Here, we review not only regulations of epigenetic modifications
during development of the placenta, but also the influences of environmental
factors. The potential value for diagnosis and treatment is also discussed.
PMID- 28420607
TI - The research progress of farm animal genomics based on sequencing technologies.
AB - Various farm animal breeds have been domesticated and bred for thousands years,
and they provide adequate animal-derived proteins to meet the human nutrition
requirement. Although quantitative genetics was applied in animal breeding, which
launched a technological revolution in the past century, a number of complex
traits remain difficult to be selected based on pedigree derived breeding, due to
complicated animal genetics and development mechanisms. Farm animal's genetic
potential hasn't yet to be fully exploited. The concept and technology from the
Human Genome Project have greatly promoted farm animal genomic researches. It is
possible to fine map the causal variations at the whole genome level and then
exploit their biological functions, thus providing the theoretical basis for
molecular designed breeding. In this review, we summarize the genomics research
progress of main farm animals during the past decade, including pigs, cattle,
yaks, goats, sheep, chickens, ducks and geese. We focus on the reference genome
sequencing and follow-up population-level genomic studies based on high
throughput resequencing technologies, and meanwhile envision the future work of
farm animal genomics.
PMID- 28420608
TI - The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking
and stress response.
AB - Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on
the plasma membrane. PIPs transfer water, CO2 and small uncharged solutes through
the plasma membrane. PIPs have high selectivity to substrates, suggestive of a
central role in maintaining cellular water balance. The expression, activity and
localization of PIPs are regulated at the transcriptional and post-translational
levels, and also affected by environmental factors. Numerous studies indicate
that the expression patterns and localizations of PIPs can change in response to
abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking,
transcriptional and post-translational regulations, and abiotic stress responses.
Moreover, we also discuss the current research trends and future directions on
PIPs.
PMID- 28420609
TI - Molecule mechanism for regulating stomatal development in plants.
AB - Stomata are small adjustable pores on the surface (epidermis) of land plants that
act as a main conduit for gas exchange. They not only play an essential role in
photosynthesis of green plants but also exert an important influence on the
global carbon and water cycle. There are great differences between monocots and
dicots in distribution and morphological structure of the stomata, affecting the
species-specific regulation of stomatal development. In this review, we summarize
the molecular regulation networks associated with stomatal precursor cell fate
determination and the epigenetic mechanisms on regulation of polar cell division.
We also outline the stomatal development processes mediated by crosstalk between
exogenous and intrinsic signals, and propose a model of multilevel regulation of
stomatal development.
PMID- 28420610
TI - The diversity of DNA fragment editing by CRISPR/Cas9 in highly homologous or
repetitive sequences.
AB - In complex genomes, there are a large number of duplicated genes in the coding
regions and many more repetitive sequences in the non-coding regions. Repetitive
sequences can exert great impacts on the heredity and evolution of the organisms,
as well as their genome 3D architecture and transcriptional regulation. The high
homology nature of repetitive sequences renders their editing by CRISPR/Cas9 very
complex. At diploid or polyploid situations, such repetitive sequences could be
edited differently on each chromosome or chromatid. To explore such
possibilities, we had studied the editing of two highly homologous DNA fragments
(L1 and L2), each about 300 bp in size and 11 kb apart on the same chromosome. We
designed a pair of sgRNAs targeting the upstream and downstream of the two DNA
fragments to guide the Cas9 cleavage of the two fragments in the human HepG2
cells. We further established single-cell CRISPR clones for DNA-fragment-edited
cells. A total of 22 CRISPR cell clones were characterized for their DNA fragment
editing patterns. In addition to the deletion of L1/L2 fragments, we had also
identified the deletion of the large internal fragment between L1 and L2
fragments, and the various combinations of inversions and deletions of the three
DNA fragments. Our results have demonstrated the potential issues with important
implications for using CRISPR/Cas9 to edit duplicated genes or repetitive
sequences in diploid or polyploid species or cell lines.
PMID- 28420611
TI - Characterization of the conbercept gene localization in DHFR- amplified CHO cells
using fluorescence in situ hybridization.
AB - Chinese-hamster ovary (CHO) cells are most widely used for mammalian protein
expression. After integration into the CHO genome, the exogenous gene may be lost
in the process of large-scale protein production due to the removal of related
selection pressures. Therefore, it is necessary to test its stability in the
genome. Conbercept is a fusion protein that specifically binds to the various
isoforms of vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental
growth factor (PlGF), thereby exerting anti-angiogenic activities. It has been
approved for Phase III clinical trials in the United States. In this study,
fluorescence in situ hybridization (FISH) was used to localize the conbercept
gene in dihydrofolatereductase (DHFR)-amplified CHO cell lines. Metaphase FISH
showed that genomic integration of the conbercept gene was stable after 4 and 19
passages, and manifested three characteristics: first, the gene locates on one
chromosome, rather than a number of chromosomes; second, the gene locates on the
longer chromosomes; third, there are many copies located on the same chromosome.
At the same time, the copy number of the conbercept gene in the CHO genome and
the conbercept protein expression levels are also stable, as verified by qPCR and
ELISA assays, respectively. These experiments demonstrated that the conbercept
gene remained stable in the genome after 19 passages, and could be actively
expressed, which strongly support the mass production and the quality control of
conbercept.
PMID- 28420612
TI - Identification and analysis of ZFPM2 as a target gene of miR-17-92 cluster in
chicken.
AB - The miR-17-92 cluster plays important roles in a variety of physiological and
pathological processes in mammals. Previously, we showed that miR-17-92 cluster
promotes chicken preadipocyte proliferation; however, the mechanism for its
action is unknown. In order to explore the mechanism by which miR-17-92 cluster
promotes chicken preadipocyte proliferation, CCK8 proliferation assay was
performed to determine the effect of ZFPM2 knockdown on chicken preadipocyte
proliferation. The results showed that ZFPM2 knockdown significantly promoted
chicken preadipocyte proliferation (P<0.01). Consistent with the CCK8 results,
the mRNA levels of cell proliferation marker genes, i.e., Cyclin D1, PCNA and
Ki67, were markedly increased in the si-ZFPM2-transfected preadipocytes (P<0.01
or P<0.05). Bioinformatics analysis showed that there were two potential miRNA
binding sites for the four individual members of miR-17-92 cluster in the ZFPM2
3'UTR, one for miR-17-5p and miR-20a and the other for miR-19a and miR-19b. To
test whether ZFPM2 is a target for the miR-17-92 cluster, the ZFPM2 3'UTR
reporter (psi-CHECK2-ZFPM2-3'UTR-WT) and its mutant reporter (psi-CHECK2-ZFPM2
3'UTR-MUT) were constructed. Reporter assays showed that overexpression of miR-17
92 cluster significantly inhibited the luciferase reporter activity of psi-CHECK2
ZFPM2-3'UTR-WT (P<0.01), as compared with control vector (empty pcDNA3.1).
Transfection of miR-17-5p, miR-19a and miR-20a inhibitors increased the reporter
activities of psi-CHECK2-ZFPM2-3'UTR-WT (P<0.01 or P<0.05). In contrast,
transfection of miR-17-5p, miR-19a, and miR-20a inhibitors had no obvious effect
on reporter activity of psi-CHECK2-ZFPM2-3'UTR-MUT. Further qRT-PCR analysis
showed that miR-17-5p, miR-20a and miR-19a inhibitors significantly elevated the
endogenous ZFPM2 mRNA expression (P<0.01 or P<0.05). Cotransfection of either miR
17-5p or miR-19a inhibitor and siZFPM2 showed that both inhibitors tended to
reduce only slightly the promoting effect of siZFPM2 on chicken preadipocyte
proliferation. Taken together, these data demonstrated that ZFPM2 is a target of
miR-17-5p, miR-20a, miR-19a, and miR-19b, and that miR-17-92 cluster promotes
chicken preadipocyte proliferation at least in part by targeting ZFPM2 and
inhibiting its expression.
PMID- 28420613
TI - Genetic analysis and identification of candidate genes for two spotted-leaf
mutants (spl101 and spl102) in rice.
AB - Spotted-leaf mutants form spots in leaves or leaf sheaths under normal condition.
The spotted-leaf phenotypes are similar to hypersensitive reaction of plants
attacked by pathogen. Identification and characterization of the spotted-leaf
mutants are helpful for understanding the mechanisms of resistance to plant
diseases. Here, we identify two spotted-leaf mutants spl101 and spl102 from an
EMS-treated elite japonica cultivar KYJ (Kuanyejing). spl101 and spl102 form
serious spots at the late heading stage. Genetic analyses show that the spotted
leaf phenotypes of both spl101 and spl102 are caused by a single recessive
mutation, respectively. By employing the Mutmap method, we reveal that both
spl101 and spl102 contain mutations in the OsEDR1 gene. The spl101 mutation
occurs in the 5 degrees -splicing site of the 6th intron of OsEDR1, which causes
abnormal recognition of the 6th intron and leads to the frameshift mutation. The
spl102 mutant contains a mutation in the tenth exon of OsEDR1, resulting in an
amino acid change from the phenylalanine (F) to the cysteine (C). OsEDR1 has been
reported to regulate pathogen-resistant reaction, and loss of OsEDR1 function
produces similar phenotypes to those of spl101 and spl102. Here, two newly
identified alleles of OsEDR1 will be benefit for further understanding the
molecular mechanisms of the OsEDR1 gene in disease resistance, and will be
helpful for enriching the rice germplasm resources. In addition, our results also
validate the effectiveness of the Mutmap method in cloning the candidate
mutations.
PMID- 28420614
TI - Applications of genome editing tools in precision medicine research.
AB - The emergence of genome editing tools, such as the clustered regularly
interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system,
has enabled researchers to achieve somatic and germline genomic manipulations in
cell lines and model organisms. Within a couple of years, genome editing is now
being rapidly developed for multiple applications and widely used in biomedical
researches, including creation of disease models with desired genetic mutations,
screening in a high-throughput manner for drug resistance genes, and making
appropriate editions to genes in vivo for disease treatment. All these
applications have been facilitating the development of precision medicine
research. In this review, we describe the use of genome editing technologies for
a variety of research and translational applications in the precision medicine
field. We also highlight some of the existing limitations or challenges as well
as future directions.
PMID- 28420615
TI - The mechanism and clinical significance of long noncoding RNA-mediated gene
expression via nuclear architecture.
AB - Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts
exceeding 200 nucleotides in length. Accumulating evidence achieved by several
sophisticated techniques such as chromatin conformation capture and RNA-seq has
led to new questions concerning correlations between lncRNAs and chromatin
structures. Many studies have revealed that lncRNAs exert great influences on
gene expression through regulating chromatin 3D structures. In addition, lncRNAs
play a crucial role in tumorigenesis and therefore hold great promises in disease
diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs
regulate gene expression by modulating nuclear architecture and discussing
clinical values of lncRNAs in oncotherapy.
PMID- 28420616
TI - Aberrant RNA splicing as the molecular basis of some pathogenic variants.
AB - Identification and correct classification of disease-associated mutations are
essential for molecular diagnosis and clinical management of many genetic
disorders. Although next-generation sequencing has greatly accelerated the
detection of nucleotide changes, the biological interpretation of most variants
has become a real challenge. Moreover, attention is typically paid to protein
coding changes and the potential impact of exonic variants on RNA splicing is
often ignored. There is increasing evidence showing that disease-causing aberrant
RNA splicing is more widespread than currently appreciated. Here, we review the
major types of the variants involved in RNA splicing and the approaches used to
identify and characterize these variants. We hope to provide a reference for
evaluation of the effects of mutations on diseases.
PMID- 28420617
TI - Application and progress of high-throughput sequencing technologies in the
research of hereditary hearing loss.
AB - Hearing loss (HL) is the most common birth defect. Elucidating the genetic basis
of hereditary deafness can not only assist diagnosis, provide the basis for
genetic counseling and the prevention of deafness, but also bring a deeper
understanding of the disease pathogenesis. In the genomic era, high-throughput
sequencing technologies, represented by whole genome sequencing (WGS), whole
exome sequencing (WES) or target region sequencing, have been widely used in the
studies of hereditary HL. Here, we summarize the application and progress of WES
and target region sequencing in the research of causative genes and clinical
molecular diagnosis of hereditary HL, hoping to be helpful for the development
and improvement of clinical genetic diagnosis of deafness in China.
PMID- 28420618
TI - Research progress on liquid biopsy in oncology and its clinical applications.
AB - Liquid biopsy is an emerging and promising detection tool for cancer, with the
benefit of being non-invasive and convenient. It analyzes tumor-derived
information in the blood or other body fluids including circulating tumour cells
(CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion
of liquid biopsy research contents and the development of capture and detection
technologies, liquid biopsy is increasingly utilized in clinical applications,
promoting the development of tumor precision medicine. Here, we mainly focus on
reviewing the objects and technologies about liquid biopsy, as well as its
applications, development and challenges in clinical practices.
PMID- 28420619
TI - Analysis of variants in upstream open reading frames of human globin-related
genes.
AB - beta-thalassemia is an autosomal recessive monogenic disease that is caused by
defects in the production of beta-like globin chains. Activation of gamma-globin
gene and the increase in fetal hemoglobin expression have been demonstrated as
one of the most important factors to ameliorate the clinical outcome of beta
thalassemia patients. In this study, 202 genes or miRNAs associated with human
hemoglobin gene expression from 1802 beta-thalassemia patients were analyzed with
target capture and next generation sequencing strategies in terms of functional
variants that might affect hemoglobin gene expression. The subsequent
bioinformatics analysis included assessments of sequence quality, the variants
within the target regions and the 5'UTR with potential effects on upstream open
reading frames (uORFs). Among the 41 variants in 5'UTR potentially affecting the
uORFs identified in the study, two variants (chr19: 41859418 G > A and
chr1:153606541 C > T) were experimentally validated with dual-luciferase assays
to be capable of significantly down-regulating the expression of TGFB1 and CHTOP
gene, respectively. The present study demonstrated a system suitable for
evaluating the importance of variants in 5'UTRs affecting uORFs in 202 human
genes associated with hemoglobin expression. Research with this approach could
provide potential targets that may contribute to the clinical phenotypes and
provide biomarkers for precise diagnosis of beta-thalassemia.
PMID- 28420620
TI - Identification of LRP5 mutations in families with familial exudative
vitreoretinopathy.
AB - Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease
characterized by defects in the development of periphery retinal vessels.
However, the clinical phenotypes of FEVR vary widely from asymptomatic to
complete blindness. We analyzed patients from three Chinese families and one
sporadic patient with FEVR to investigate the clinical features and disease
causing mutations. Ocular phenotypes included increased ramification of the
peripheral retinal vessels, a peripheral avascular zone, inferotemporal dragging
of the optic disc and macula, and retinal folds. Peripheral blood DNA samples
were obtained from patients with FEVR and their family members. Primers were
designed to amplify the coding exons and adjacent intronic regions of the FEVR
causing genes FZD4, LRP5, NDP and TSPAN12. By polymerase chain reactions, each
amplicon was subjected to direct Sanger sequencing analysis. Potential pathogenic
changes of the sequence variants were analyzed by the orthologous protein
sequence alignment and computational prediction software. We identified five LRP5
mutations: three novel heterozygous mutations-p.M181R, p.R399S and p.G503R and
two known mutations that were never reported in FEVR patients: p.R494Q and
p.G876S. All five mutations involved highly conserved residues and were predicted
to be damaging by SIFT and PolyPhen-2. None was present in 500 normal
individuals. To assess the pathogenesis of these mutations, wild-type and all
five mutant LRP5 proteins were assayed for the ability to activate the
Norrin/beta-catenin pathway by established luciferase reporter assays, and all
mutants failed to activate the pathway. This study extends the genetic database
of the FEVR disease in China and provides a basis for molecular diagnosis of the
disease.
PMID- 28420621
TI - Association between polymorphisms of autophagy pathway and responses in non-small
cell lung cancer patients treated with platinum-based chemotherapy.
AB - Platinum-based chemotherapy is an important treatment for non-small cell lung
cancer. However, the effectiveness of the treatment varies among the patients. We
investigated the association between DNA polymorphisms of the autophagy pathway
and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs
located on 13 genes of the autophagy pathway were genotyped and assessed for
their association with clinical benefit, progression-free survival (PFS) and
overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR:
0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45
0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26
2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A)
(P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with
clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI:
0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM
gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene
were significantly associated with PFS. We also found that rs7953348 (G>A)
(P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A)
(P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS.
Thus, the study demonstrated that the autophagy pathway might play important
role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes
can potentially be predictors for clinical responses of platinum-based
chemotherapy among the patients with non-small lung cancer.
PMID- 28420623
TI - Externalised locking compression plate as an alternative to the unilateral
external fixator: a biomechanical comparative study of axial and torsional
stiffness.
AB - OBJECTIVES: External fixators are the traditional fixation method of choice for
contaminated open fractures. However, patient acceptance is low due to the high
profile and therefore physical burden of the constructs. An externalised locking
compression plate is a low profile alternative. However, the biomechanical
differences have not been assessed. The objective of this study was to evaluate
the axial and torsional stiffness of the externalised titanium locking
compression plate (ET-LCP), the externalised stainless steel locking compression
plate (ESS-LCP) and the unilateral external fixator (UEF). METHODS: A fracture
gap model was created to simulate comminuted mid-shaft tibia fractures using
synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS
LCP or UEF (five constructs each). The constructs were loaded under both axial
and torsional directions to determine construct stiffness. RESULTS: The mean
axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while
it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA)
testing in all three groups demonstrated no significant difference (F(2,12) =
2.057, p = 0.171).There was a significant difference in mean torsional stiffness
between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP
(0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A
Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was
statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No
catastrophic failures were observed. CONCLUSION: Using the LCP as an external
fixator may provide a viable and attractive alternative to the traditional UEF as
its lower profile makes it more acceptable to patients, while not compromising on
axial and torsional stiffness.Cite this article: B. F. H. Ang, J. Y. Chen, A. K.
S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe.
Externalised locking compression plate as an alternative to the unilateral
external fixator: a biomechanical comparative study of axial and torsional
stiffness. Bone Joint Res 2017;6:216-223. DOI: 10.1302/2046-3758.64.2000470.
PMID- 28420624
TI - Five minutes with . . . Susan Lanham-New.
PMID- 28420625
TI - Sixty seconds on . . . teen pregnancies.
PMID- 28420627
TI - Encouraging young and old to interact in care settings.
PMID- 28420628
TI - Liposuction-induced fat embolism syndrome.
PMID- 28420630
TI - Ruth Kennedy.
PMID- 28420629
TI - Dexamethasone versus standard treatment for postoperative nausea and vomiting in
gastrointestinal surgery: randomised controlled trial (DREAMS Trial).
AB - : Objectives To determine whether preoperative dexamethasone reduces
postoperative vomiting in patients undergoing elective bowel surgery and whether
it is associated with other measurable benefits during recovery from surgery,
including quicker return to oral diet and reduced length of stay.Design Pragmatic
two arm parallel group randomised trial with blinded postoperative care and
outcome assessment.Setting 45 UK hospitals.Participants 1350 patients aged 18 or
over undergoing elective open or laparoscopic bowel surgery for malignant or
benign pathology.Interventions Addition of a single dose of 8 mg intravenous
dexamethasone at induction of anaesthesia compared with standard care.Main
outcome measures Primary outcome: reported vomiting within 24 hours reported by
patient or clinician. SECONDARY OUTCOMES: vomiting with 72 and 120 hours reported
by patient or clinician; use of antiemetics and postoperative nausea and vomiting
at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120
hours or discharge and at 30 days; time to return to fluid and food intake;
length of hospital stay; adverse events.Results 1350 participants were recruited
and randomly allocated to additional dexamethasone (n=674) or standard care
(n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred
in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated
standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22;
P=0.003). Additional postoperative antiemetics were given (on demand) to 265
(39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard
care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to
72 hours. There was no increase in complications.Conclusions Addition of a single
dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly
reduces both the incidence of postoperative nausea and vomiting at 24 hours and
the need for rescue antiemetics for up to 72 hours in patients undergoing large
and small bowel surgery, with no increase in adverse events.Trial registration
EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).
PMID- 28420631
TI - Health secretary orders inquiry into babies' deaths at Shrewsbury and Telford.
PMID- 28420632
TI - Paediatric traumatic pneumomediastinum: the spinnaker sail sign.
PMID- 28420633
TI - Fibrin sheath-associated endovascular infection of the heart: the Trojan horse of
indwelling central venous catheters.
AB - Chronic indwelling central venous catheters can result in formation of fibrin
sheaths increasing risk of occlusion, thrombosis and infection. Endovascular
infection of right-sided heart structures induced by such sheaths is very rare. A
48-year-old woman with end-stage renal disease initially treated for diabetic
ketoacidosis developed persistent Staphylococcus epidermidis bacteraemia without
an identifiable source. Although transthoracic echocardiography was unremarkable,
transoesophageal echocardiography revealed a fibrin sheath and vegetations in
superior vena cava-right atrium junction, which was the site of the tip of a
central catheter that had been removed 2 months prior, consistent with fibrin
sheath-associated endovascular infection. The bacteraemia cleared and clinical
improvement was seen with prolonged intravenous vancomycin. In patients with
unexplained bacteraemia and history of a central catheter, rare causes of
endovascular infections of right-sided heart structures like fibrin sheaths
should be considered. These can persist months after catheter removal.
Transoesophageal echocardiogram should be used for earlier detection.
PMID- 28420634
TI - Making the NHS and social care system sustainable.
PMID- 28420636
TI - Thomas George Price.
PMID- 28420635
TI - Lower urinary tract symptoms in an older man.
PMID- 28420637
TI - GPs urged to be cautious when assessing patients' fitness for endurance sports.
PMID- 28420638
TI - The BMJ Awards 2017: Cardiology.
PMID- 28420639
TI - Implementing shared decision making in the NHS: lessons from the MAGIC programme.
PMID- 28420640
TI - Margaret McCartney: Why ask, if you ignore the answer?
PMID- 28420641
TI - Should we intubate patients during cardiopulmonary resuscitation?
PMID- 28420642
TI - Vanguards start to change practice but will lessons be applied nationwide?
PMID- 28420643
TI - Isolated implant metastasis in chest wall due to seeding of transpleurally placed
PTBD catheter tract in a case of hilar cholangiocarcinoma.
AB - Percutaneous transhepatic biliary drainage (PTBD) catheter site metastasis in
cases of cholangiocarcinoma is reported sporadically. But it is unusual to see
left-sided tumour metastasising to the right PTBD catheter site. Metastasis, in
general, has a poor prognosis, but recurrence along the catheter tract in the
absence of other systemic diseases can be a different scenario altogether. To
date, there is no consensus on the management of this form of metastasis. But
carefully selected patients can benefit from aggressive surgical resection. We
report a case of a young patient with isolated chest wall metastasis 1 year after
resection of left-sided hilar cholangiocarcinoma. The metastasis was resected
and, on pathological analysis, was confirmed to be due to implantation of
malignant cells along the tract of the PTBD catheter placed via a transpleural
route.
PMID- 28420644
TI - Smokers and Postcessation Weight Gain After Acute Coronary Syndrome.
AB - BACKGROUND: Smoking cessation and weight management are recommended after acute
coronary syndrome (ACS); however, little is known about the effects of smoking
cessation on weight change after ACS. We aimed to assess the effect of smoking
cessation after ACS on weight over a 12-month follow-up period. METHODS AND
RESULTS: Data were prospectively collected from the EVITA (Evaluation of
Varenicline in Smoking Cessation for Patients Post-Acute Coronary Syndrome)
trial. Weight change was compared among 3 groups of patients: those who were
completely abstinent (n=70), those who smoked intermittently (n=68), and those
who smoked persistently (n=34). Patients' mean baseline weight was 83.9 kg (SD
17.7) with a mean body mass index of 28.5 (SD 5.4). Patients smoked a mean of
37.7 years (SD 17.7) and a mean of 21.0 cigarettes (SD 9.0) per day prior to
their ACS. Weight change varied across groups, with abstainers gaining a mean of
4.8 kg (SD 8.6), intermittent smokers gaining a mean of 2.0 kg (SD 8.9) and
persistent smokers losing a mean of 0.7 kg (SD 7.4). At 52 weeks, abstainers were
more likely to gain weight than persistent smokers (difference in means 5.5 kg;
95% CI 2.3-8.8). This weight gain was not associated with an increase in the use
of antihypertensive or antidiabetic medications. CONCLUSIONS: Following an ACS,
significant weight is gained by patients who quit smoking. Weight-management
interventions among smokers who quit after ACS should be a focus of investigation
in future research so that the cardiovascular benefits achieved by smoking
cessation are not offset by weight gain in this high-risk population. CLINICAL
TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT00794573.
PMID- 28420645
TI - Association Between Chronic Kidney Disease and Rates of Transfusion and
Progression to End-Stage Renal Disease in Patients Undergoing Transradial Versus
Transfemoral Cardiac Catheterization-An Analysis From the Veterans Affairs
Clinical Assessment Reporting and Tracking (CART) Program.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for
bleeding, transfusion, and dialysis after cardiac catheterization. Whether rates
of these complications are increased in this high-risk population undergoing
transradial access compared with transfemoral access is unknown. METHODS AND
RESULTS: From the Veterans Affairs (VA) Clinical Assessment Reporting and
Tracking program, we identified 229 108 patients undergoing cardiac
catheterization between 2007 and 2014, of which 48 155 (21.0%) had baseline
glomerular filtration rate (GFR) between 15 and 59 mL/min. We used multivariable
Cox modeling to determine the independent association between transradial access
and postprocedure transfusion as well as progression to new dialysis by degree of
renal dysfunction. Overall, 35 979 (15.7%) of patients underwent Transradial
access. Transradial patients tended to be slightly younger, but, overall, had
similar rates of CKD compared to transfemoral patients (24.3% vs 27.1%).
Transradial patients had longer fluoroscopy times (7.2 vs 6.0 minutes; P<0.001),
but lower contrast use (85.0 vs 100.0 mL; P<0.001). The estimated rate of blood
transfusion within 48 hours was lower among transradial patients (0.85% vs 1.01%)
as were rates of new dialysis at 1 year (0.58% vs 0.71%). After multivariable
adjustment, transradial access was associated with lower rates of progression to
dialysis at 1 year overall (hazard ratio [HR], 0.83; 95% CI, 0.70-0.98), with no
trend of increased risk for dialysis by degree of CKD compared with transfemoral
access. Transradial access was associated with greater reduction in transfusion
rates with increasing degree of CKD (P value for trend=0.04: non-CKD: HR, 0.99;
95% CI, 0.73-1.34; GFR 45-59 mL/min: HR, 0.93; 95% CI, 0.70-1.23; GFR 30-44
mL/min: HR, 0.73; 95% CI, 0.51-1.03; GFR 15-29 mL/min: HR, 0.43; 95% CI, 0.20
0.90). CONCLUSIONS: Among patients undergoing cardiac catheterization in the VA
health system, transradial access was associated with lower risk for
postprocedure transfusion within 48 hours among patients with more-severe CKD,
and with lower risk of progression to end-stage renal disease at 1 year compared
with transfemoral access. These data provide additional evidence that transradial
access may provide significant benefit in this high-risk population.
PMID- 28420646
TI - Associations Between Left Ventricular Dysfunction and Brain Structure and
Function: Findings From the SABRE (Southall and Brent Revisited) Study.
AB - BACKGROUND: Subclinical left ventricular (LV) dysfunction has been inconsistently
associated with early cognitive impairment, and mechanistic pathways have been
poorly considered. We investigated the cross-sectional relationship between LV
dysfunction and structural/functional measures of the brain and explored the role
of potential mechanisms. METHOD AND RESULTS: A total of 1338 individuals (69+/-6
years) from the Southall and Brent Revisited study underwent echocardiography for
systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial
diameter) assessment. Cognitive function was assessed and total and hippocampal
brain volumes were measured by magnetic resonance imaging. Global LV function was
assessed by circulating N-terminal pro-brain natriuretic peptide. The role of
potential mechanistic pathways of arterial stiffness, atherosclerosis,
microvascular disease, and inflammation were explored. After adjusting for age,
sex, and ethnicity, lower systolic function was associated with lower total brain
(beta+/-standard error, 14.9+/-3.2 cm3; P<0.0001) and hippocampal volumes (0.05+/
0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working
memory (-0.21+/-0.07, P=0.004) and fluency scores (-0.18+/-0.08, P=0.02). Reduced
global LV function was associated with smaller hippocampal volume (-0.10+/-0.03
cm3, P=0.004) and adverse visual memory (-0.076+/-0.03, P=0.02) and processing
speed (0.063+/-0.02, P=0.006) scores. Separate adjustment for concomitant
cardiovascular risk factors attenuated associations with hippocampal volume and
fluency only. Further adjustment for the alternative pathways of microvascular
disease or arterial stiffness attenuated the relationship between global LV
function and visual memory. CONCLUSIONS: In a community-based sample of older
people, measures of LV function were associated with structural/functional
measures of the brain. These associations were not wholly explained by
concomitant risk factors or potential mechanistic pathways.
PMID- 28420647
TI - Incremental Value of Transthoracic Doppler Echocardiography-Assessed Coronary
Flow Reserve in Patients With Suspected Myocardial Ischemia Undergoing Myocardial
Perfusion Scintigraphy.
AB - BACKGROUND: Adenosine-assisted transthoracic Doppler-derived coronary flow
reserve (TDE-CFR) reflects coronary vascular function. The prognostic and
incremental value of left anterior descending coronary artery TDE-CFR above
myocardial perfusion scintigraphy in patients with suspected myocardial ischemia
has not yet been studied. METHODS AND RESULTS: Three hundred seventy-one patients
(mean age, 62.3+/-8.7 years; 46.8% males) referred to myocardial perfusion
scintigraphy attributed to suspected myocardial ischemia were included in the
study. The TDE-CFR result was blinded to the referring physician. Patients were
followed up regarding major cardiovascular events, defined as cardiovascular
death, myocardial infarction, or acute revascularization during a median follow
up time of 4.5 years. A TDE-CFR value of <=2.0 was considered reduced. Major
cardiovascular events occurred during follow-up in 60 patients (16.2%). A reduced
TDE-CFR was detected in 76 patients (20.5%). Patients with reduced TDE-CFR had an
event rate of 36.8% compared to 10.8% in patients with normal TDE-CFR (unadjusted
hazard ratio, 4.63; 95% CI, 2.78-7.69; P<0.001). In a multivariate model, TDE-CFR
remained a significant independent predictor of major cardiovascular events. The
major cardiovascular events rate was 7.5% in patients without myocardial
perfusion scintigraphy-detected myocardial ischemia and normal TDE-CFR (n=200),
24.2% in patients without ischemia but with reduced TDE-CFR (n=33), and 46.5% in
patients with both myocardial perfusion scintigraphy-detected myocardial ischemia
and a reduced TDE-CFR (n=43; P<0.001). CONCLUSIONS: Coronary microvascular
dysfunction, as determined by TDE-CFR, is a strong independent predictor of
cardiovascular events and adds incremental prognostic value compared with
myocardial perfusion scintigraphy. The current study supports routine assessment
of CFR in patients with suspected ischemic heart disease.
PMID- 28420648
TI - Association of Magnet Status With Hospitalization Outcomes for Ischemic Stroke
Patients.
AB - BACKGROUND: It is not clear whether Magnet recognition by the American Nurses
Credentialing Center (nursing excellence program) is associated with improved
patient outcomes. We investigated whether hospitalization in a Magnet hospital is
associated with improved outcomes for patients with ischemic stroke. METHODS AND
RESULTS: We performed a cohort study of patients with ischemic stroke from 2009
to 2013, who were registered in the New York Statewide Planning and Research
Cooperative System database. Propensity-score-adjusted multivariable regression
models were used to adjust for known confounders, with mixed effects methods to
control for clustering at the facility level. An instrumental variable analysis
was used to control for unmeasured confounding and simulate the effect of a
randomized trial. During the study period, 176 557 patients were admitted for
ischemic stroke, and met the inclusion criteria. Of these, 32 092 (18.2%) were
hospitalized in Magnet hospitals, and 144 465 (81.8%) in non-Magnet institutions.
Instrumental variable analysis demonstrated that hospitalization in Magnet
hospitals was associated with lower case-fatality (adjusted difference, -23.9%;
95% CI, -29.0% to -18.7%), length of stay (adjusted difference, -0.4; 95% CI,
0.8 to -0.1), and rate of discharge to a facility (adjusted difference, -16.5%;
95% CI, -20.0% to -13.0%) in comparison to non-Magnet hospitals. The same
associations were present in propensity-score-adjusted mixed effects models.
CONCLUSIONS: Using a comprehensive all-payer cohort of patients with ischemic
stroke in New York State, we identified an association of treatment in Magnet
hospitals with lower case-fatality, discharge to a facility, and length of stay.
Further research into the factors contributing to the superiority of Magnet
hospitals in stroke care is warranted.
PMID- 28420649
TI - A sandwich ELISA for measurement of the primary glucagon-like peptide-1
metabolite.
AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the
gastrointestinal tract. It is best known for its glucose-dependent insulinotropic
effects. GLP-1 is secreted in its intact (active) form (7-36NH2) but is rapidly
degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the
primary metabolite (9-36NH2) before reaching the targets via the circulation.
Although originally thought to be inactive or antagonistic, GLP-1 9-36NH2 may
have independent actions, and it is therefore relevant to be able to measure it.
Because reliable assays were not available, we developed a sandwich ELISA
recognizing both GLP-1 9-36NH2 and nonamidated GLP-1 9-37. The ELISA was
validated using analytical assay validation guidelines and by comparing it to a
subtraction-based method, hitherto employed for estimation of GLP-1 9-36NH2 Its
accuracy was evaluated from measurements of plasma obtained during intravenous
infusions (1.5 pmol * kg-1 * min-1) of GLP-1 7-36NH2 in healthy subjects and
patients with type 2 diabetes. Plasma levels of the endogenous GLP-1 metabolite
increased during a meal challenge in patients with type 2 diabetes, and treatment
with a DPP-4 inhibitor fully blocked its formation. Accurate measurements of the
GLP-1 metabolite may contribute to understanding its physiology and role of GLP-1
in diabetes.
PMID- 28420651
TI - Anorectal involvement in a patient with multiple myeloma.
AB - Multiple myeloma is a neoplastic proliferation of monoclonal plasma cells.
Symptomatic gastrointestinal involvement is uncommon. We report the case of a 45
year-old patient admitted with an anorectal polypoid lesion, which progressed to
colonic obstruction. Investigation revealed a secondary plasmacytoma associated
with multiple myeloma. We discuss the characteristics of this rare entity with
poor prognosis, its clinical implications and treatment options.
PMID- 28420650
TI - Changes in LXR signaling influence early-pregnancy lipogenesis and protect
against dysregulated fetoplacental lipid homeostasis.
AB - Human pregnancy is associated with enhanced de novo lipogenesis in the early
stages followed by hyperlipidemia during advanced gestation. Liver X receptors
(LXRs) are oxysterol-activated nuclear receptors that stimulate de novo
lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues
followed by its transport back to the liver for biliary excretion. Although LXR
is recognized as a master regulator of triglyceride and cholesterol homeostasis,
it is unknown whether it facilitates the gestational adaptations in lipid
metabolism. To address this question, biochemical profiling, protein
quantification, and gene expression studies were used, and gestational metabolic
changes in T0901317-treated wild-type mice and Lxrab-/- mutants were
investigated. Here, we show that altered LXR signaling contributes to the
enhanced lipogenesis in early pregnancy by increasing the expression of hepatic
Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of
LXR with T0901317 and the genetic ablation of its two isoforms disrupted the
increase in hepatic fatty acid biosynthesis and the development of
hypertriglyceridemia during early gestation. We also demonstrate that absence of
LXR enhances maternal white adipose tissue lipolysis, causing abnormal
accumulation of triglycerides, cholesterol, and free fatty acids in the fetal
liver. Together, these data identify LXR as an important factor in early
pregnancy lipogenesis that is also necessary to protect against abnormalities in
fetoplacental lipid homeostasis.
PMID- 28420653
TI - David Oliver: Choosing to be honest about patient choice.
PMID- 28420652
TI - Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER
Consortium.
AB - Background: Alcohol is a recognized risk factor for invasive breast cancer, but
few studies involve African American women.Methods: The current analysis included
22,338 women (5,108 cases of invasive breast cancer) from the African American
Breast Cancer Epidemiology and Risk (AMBER) Consortium. The association between
number of alcoholic drinks per week (dpw) and breast cancer was estimated using
logistic regression, adjusting for potential confounders, and stratifying by
breast cancer subtype.Results: Approximately 35% of controls were current
drinkers at interview. Women who reported current drinking of >=14 dpw had an
elevated risk of breast cancer compared with light drinkers (>0-<4 dpw) [adjusted
OR (ORadj), 1.33; 95% confidence interval (CI), 1.07-1.64]. We observed elevated
risk among women drinking >=7 dpw for ER - [ORadj, 1.31; 95% CI, 1.00-1.72], PR -
[ORadj, 1.28; 95% CI, 1.00-1.63], HER2 - [ORadj, 1.36; 95% CI, 1.09-1.70], and
triple-negative [ORadj, 1.39; 95% CI, 0.98-2.00] molecular subtype. Among
receptor-positive cases, ORs remained elevated but attenuated relative to
receptor-negative cases. Sensitivity analysis of age-defined windows of exposure
(<30 years, 30-49, 50+ years of age) did not reveal variation in patterns of
association. Risk associated with alcohol intake did not vary significantly by
oral contraceptive use, smoking status, or menopausal status.Conclusions: Among
African American women, similar to women of European descent, drinking >=7
alcoholic dpw was associated with an increased risk of breast cancer regardless
of subtype.Impact: Alcohol intake is a modifiable risk factor for breast cancer,
and reduced intake among African American women should be encouraged. Cancer
Epidemiol Biomarkers Prev; 26(5); 787-94. (c)2017 AACR.
PMID- 28420654
TI - Changes in the Profile of Endovascular Procedures Performed in Freestanding
Dialysis Access Centers over 15 Years.
AB - BACKGROUND AND OBJECTIVES: Marked changes occurred in the vascular access profile
of patients receiving hemodialysis in the United States over the 15-year period
of 2001-2015. This study was undertaken to evaluate how these changes have
affected dialysis access maintenance and salvage procedures performed in
freestanding dialysis access centers and to examine the effectiveness,
efficiency, and safety of these procedures in this setting. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: Data were collected from freestanding, dedicated
dialysis access centers operating under a common system of management. Data were
available on 689,676 dialysis access procedures. Data relating to case mix,
procedure outcome, procedural time, and intraprocedural and immediate
postprocedural complications were analyzed. RESULTS: The arteriovenous procedure
profile changed from one characterized by approximately equal numbers of
angioplasties and thrombectomies performed on arteriovenous grafts (AVGs) to one
characterized primarily by angioplasties performed on arteriovenous fistulas. The
percentage of angioplasties performed throughout the study was significantly
greater than thrombectomies, with a mean of 67.9% versus 32.1% (P<0.001).
Interventional procedures did not decrease with increasing arteriovenous fistula
utilization in prevalent patients receiving dialysis. The incidence roughly
paralleled the increasing prevalence of this type of access. A decreasing
percentage of AVG utilization resulted in a progressive, roughly parallel, but
disproportionately higher, decrease in the percentage of AVG procedures
(P<0.001). A progressive improvement in procedure outcomes and a decrease in
complication rates and procedure times were observed (P<0.001 for each). A
progressive decrease in tunneled dialysis catheter placement was also observed.
CONCLUSIONS: The procedure profile treated in freestanding, dedicated dialysis
access centers changed significantly over 15 years, reflecting the changes that
have occurred in the vascular access profile of the dialysis population.
PMID- 28420655
TI - Syncope and Its Impact on Occupational Accidents and Employment: A Danish
Nationwide Retrospective Cohort Study.
AB - BACKGROUND: First-time syncopal episodes usually occur in adults of working age,
but their impact on occupational safety and employment remains unknown. We
examined the associations of syncope with occupational accidents and termination
of employment. METHODS AND RESULTS: Through linkage of Danish population-based
registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3
410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were
identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5),
and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up
of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an
occupational accident requiring hospitalization (2.1/100 person-years). In
multiple Poisson regression analysis, the incidence rate ratio in the employed
syncope population was higher than in the employed general population (1.44; 95%
confidence interval [CI], 1.33-1.55) and more pronounced in people with
recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of
employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the
reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen
estimator. Factors associated with termination of employment were age <40 years
(incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20;
95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational
level (2.61; 95% CI, 2.34-2.91). CONCLUSIONS: In this nationwide cohort, syncope
was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold
higher risk of termination of employment compared with the employed general
population.
PMID- 28420657
TI - A neural basis for password-based species recognition in an avian brood parasite.
AB - Obligate avian brood parasites are raised by heterospecific hosts and, therefore,
lack crucial early exposure to relatives and other conspecifics. Yet, young brood
parasites readily recognize and affiliate with others of their own species upon
independence. One solution to this social recognition paradox is the ontogenetic
'password' mechanism used by obligate parasitic brown-headed cowbirds (Molothrus
ater), whereby conspecific identification is initially mediated through the
cowbird chatter: a non-learned vocal cue. We explored the neural basis of such
password-based species recognition in juvenile and adult male cowbirds. We found
that cowbird auditory forebrain regions express greater densities of the protein
product of the immediate-early gene ZENK in response to the password chatter call
relative to control sounds of mourning dove (Zenaida macroura) coos. The chatter
selective induction of ZENK expression occurs in both the caudal medial
nidopallium (NCM) and the caudal medial mesopallium (CMM) in adults, but only
within the NCM in juveniles. In contrast, we discovered that juvenile cowbirds
exhibit neural selectivity to presentations of either conspecific or
heterospecific songs, but only in CMM and only after recent experience. Juvenile
cowbirds that did not have previous experience with the song type they were
exposed to during the test period exhibited significantly lower activity
dependent gene expression. Thus, in juvenile male cowbirds, there is early onset
of species-specific selective neural representation of non-learned calls in NCM
and recently experienced song in CMM. These results suggest that NCM is
evolutionarily co-opted in parasitic cowbirds to selectively recognize the
password chatter, allowing juvenile cowbirds to identify adult conspecifics and
avoid mis-imprinting upon unrelated host species. These ontogenetic comparisons
reveal novel insights into the neural basis of species recognition in brood
parasitic species.
PMID- 28420656
TI - Posttranslational modification impact on the mechanism by which amyloid-beta
induces synaptic dysfunction.
AB - Oligomeric amyloid-beta (Abeta) 1-42 disrupts synaptic function at an early stage
of Alzheimer's disease (AD). Multiple posttranslational modifications of Abeta
have been identified, among which N-terminally truncated forms are the most
abundant. It is not clear, however, whether modified species can induce synaptic
dysfunction on their own and how altered biochemical properties can contribute to
the synaptotoxic mechanisms. Here, we show that a prominent isoform,
pyroglutamated Abeta3(pE)-42, induces synaptic dysfunction to a similar extent
like Abeta1-42 but by clearly different mechanisms. In contrast to Abeta1-42,
Abeta3(pE)-42 does not directly associate with synaptic membranes or the prion
protein but is instead taken up by astrocytes and potently induces glial release
of the proinflammatory cytokine TNFalpha. Moreover, Abeta3(pE)-42-induced
synaptic dysfunction is not related to NMDAR signalling and Abeta3(pE)-42-induced
impairment of synaptic plasticity cannot be rescued by D1-agonists. Collectively,
the data point to a scenario where neuroinflammatory processes together with
direct synaptotoxic effects are caused by posttranslational modification of
soluble oligomeric Abeta and contribute synergistically to the onset of synaptic
dysfunction in AD.
PMID- 28420658
TI - Simple and rapid biochemical method to synthesize labeled or unlabeled
phosphatidylinositol species.
AB - Phosphatidylinositol (PI) is the precursor of many important signaling molecules
in eukaryotic cells and, most probably, PI also has important functions in
cellular membranes. However, these functions are poorly understood, which is
largely due to that i) only few PI species with specific acyl chains are
available commercially and ii) there are no simple methods to synthesize such
species. Here, we present a simple biochemical protocol to synthesize a variety
of labeled or unlabeled PI species from corresponding commercially available
phosphatidylcholines. The protocol can be carried out in a single vial in a two
step process which employs three enzymatic reactions mediated by i) commercial
phospholipase D from Streptomyces chromofuscus, ii) CDP-diacylglycerol synthase
overexpressed in E. coli and iii) PI synthase of Arabidopsis thaliana ectopically
expressed in E. coli The PI product is readily purified from the reaction mixture
by liquid chromatography since E. coli does not contain endogenous PI or other
coeluting lipids. The method allows one to synthesize and purify labeled or
unlabeled PI species in 1 or 2 days.Typically, 40-60% of (unsaturated) PC was
converted to PI albeit the final yield of PI was less (25-35%) due to losses upon
purification.
PMID- 28420659
TI - Very low expression of PD-L1 in medullary thyroid carcinoma.
PMID- 28420660
TI - Education achievement and type 2 diabetes-what mediates the relationship in older
adults? Data from the ESTHER study: a population-based cohort study.
AB - OBJECTIVE: The study aims to identify the mediating factors of the relationship
between education achievement and incident type 2 diabetes mellitus (T2DM) in
older adults. DESIGN: Population-based cohort study. SETTING: Participants were
recruited from the German federal state of Saarland. PARTICIPANTS: Participants
were excluded if they had prevalent T2DM or missing data on prevalent T2DM,
missing or zero follow-up time for incident T2DM or were under 50 years of age.
The total sample consisted of 7462 individuals aged 50-75 years (42.8% men, mean
age 61.7 years) at baseline (2000-02). The median follow-up time was 8.0 years.
METHODS: Cox proportional hazards regression was initially used to determine the
direct association between education achievement and incident T2DM. Using the
Baron and Kenny approach, we then investigated the associations between education
achievement and incident T2DM with the potential mediators. The contribution of
each of the putative mediating variables was then calculated. RESULTS: A clear
socioeconomic gradient was observed with regard to T2DM incidence with the lowest
educated individuals at a greater risk of developing the disease during the
follow-up period: HR (95% CI) high education: 0.52 (0.34 to 0.80); medium
education: 0.80 (0.66 to 0.96). Seven of the variables considered explained a
proportion of the education-T2DM relationship (body mass index, alcohol
consumption, hypertension, fasting triglycerides, high-density lipoprotein (HDL)
cholesterol, physical activity and smoking status), where the contribution of the
variables ranged from 1.0% to 17.7%. Overall, the mediators explained 31.7% of
the relationship. CONCLUSION: By identifying the possible mediating factors of
the relationship between education achievement and incident T2DM in older adults,
the results of this study can be used to assist with the development of public
health strategies that aim to reduce socioeconomic inequalities in T2DM.
PMID- 28420661
TI - Person-centred transition programme to empower adolescents with congenital heart
disease in the transition to adulthood: a study protocol for a hybrid randomised
controlled trial (STEPSTONES project).
AB - INTRODUCTION: When a young person grows up, they evolve from an independent child
to an empowered adult. If an individual has a chronic condition, this additional
burden may hamper adequate development and independence. Transition programmes
for young persons with chronic disorders aim to provide the necessary skills for
self-management and participation in care. However, strong evidence on the
effects of these interventions is lacking. Therefore, as part of the STEPSTONES
project (Swedish Transition Effects Project Supporting Teenagers with chrONic
mEdical conditionS), we propose a trial to assess the effectiveness of a
structured, person-centred transition programme to empower adolescents with
congenital heart disease in the transition to adulthood. METHODS/DESIGN:
STEPSTONES will use a hybrid experimental design in which a randomised controlled
trial is embedded in a longitudinal, observational study. It will be conducted in
4 paediatric cardiology centres in Sweden. 2 centres will be allocated to the
randomised controlled trial group, assigning patients randomly to the
intervention group (n=63) or the comparison group (n=63). The other 2 centres
will form the intervention-naive control group (n=63). The primary outcome is the
level of patient empowerment, as measured by the Gothenburg Young Persons
Empowerment Scale (GYPES). ETHICS AND DISSEMINATION: The study has been approved
by the Regional Ethical Board of Gothenburg, Sweden. Findings will be reported
following the CONSORT statement and disseminated at international conferences and
as published papers in peer-reviewed journals. TRIAL REGISTRATION NUMBER:
NCT02675361; pre-results.
PMID- 28420662
TI - Outcome of a screening programme for the prevention of neonatal invasive early
onset group B Streptococcus infection in a UK maternity unit: an observational
study.
AB - BACKGROUND: Against a background of failure to prevent neonatal invasive early
onset group B Streptococcus infections (GBS) in our maternity unit using risk
based approach for intrapartum antibiotic prophylaxis, we introduced an antenatal
GBS carriage screening programme to identify additional women to target for
prophylaxis. OBJECTIVES: To describe the implementation and outcome of an
antepartum screening programme for prevention of invasive early-onset GBS
infection in a UK maternity unit. DESIGN: Observational study of outcome of
screening programme (intervention) with comparison to historical controls
(preintervention). SETTING: Hospital and community-based maternity services
provided by Northwick Park and Central Middlesex Hospitals in North West London.
PARTICIPANTS: Women who gave birth between March 2014 and December 2015 at
Northwick Park Hospital. METHODS: Women were screened for GBS at 35-37 weeks and
carriers offered intrapartum antibiotic prophylaxis. Screening programme was
first introduced in hospital (March 2014) and then in community (August 2014).
Compliance was audited by review of randomly selected case records. Invasive
early-onset GBS infections were defined through GBS being cultured from neonatal
blood, cerebrospinal fluid or sterile fluids within 0-6 days of birth. MAIN
OUTCOME: Incidence of early-onset GBS infections. RESULTS: 6309 (69%) of the 9098
eligible women were tested. Screening rate improved progressively from 42% in
2014 to 75% in 2015. Audit showed that 98% of women accepted the offer of
screening. Recto-vaginal GBS carriage rate was 29.4% (1822/6193). All strains
were susceptible to penicillin but 11.3% (206/1822) were resistant to
clindamycin. Early onset GBS rate fell from 0.99/1000 live births (25/25276) in
the prescreening period to 0.33/1000 in the screening period (Rate Ratio=0.33;
p=0.08). In the subset of mothers actually screened, the rate was 0.16/1000 live
births (1/6309), (Rate Ratio=0.16; p<0.05). CONCLUSIONS: Our findings confirm
that an antenatal screening programme for prevention of early-onset GBS infection
can be implemented in a UK maternity setting and is associated with a fall in
infection rates.
PMID- 28420663
TI - Optimal body fat percentage cut-off values for identifying cardiovascular risk
factors in Mongolian and Han adults: a population-based cross-sectional study in
Inner Mongolia, China.
AB - OBJECTIVE: The present study was designed to determine the optimal cut-off values
of body fat percentage (BF%) for the detection of cardiovascular disease (CVD)
risk factors in Mongolian and Han adults. METHOD: This cross-sectional study
involving 3221 Chinese adults (2308 Han and 913 Mongolian) aged 20-80 years was
conducted in Inner Mongolia Autonomous Region, China, in 2014. Data from a
standardised questionnaire, physical examination and blood sample were obtained.
The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut
offs were analysed by receiver operating characteristic curves to predict the
risk of diabetes, hypertension and dyslipidaemia. Binary logistic regression
analysis was performed to evaluate the OR of each CVD risk factor according to
obesity defined by BF%. RESULTS: Mean BF% levels were lower in men than in women
(22.54+/-5.77 vs 32.95+/-6.18 in Han, 23.86+/-5.72 vs 33.98+/-6.40 in Mongolian
population, respectively; p<0.001). In Han population, the area under curve (AUC)
values for BF% ranged from 0.589 to 0.699 for men and from 0.711 to 0.763 for
women. Compared with men, AUCs for diabetes and clustering of >=2 risk factors in
women were significantly higher (p<0.05). The AUCs for BF% in women (0.685-0.783)
were similar with those in men (0.686-0.736) for CVD risk factors in Mongolian
population. In Han adults, the optimal BF% cut-off values to detect CVD risk
factors varied from 18.7% to 24.2% in men and 32.7% to 35.4% in women. In
Mongolian population, the optimal cut-off values of BF% for men and women ranged
from 21.0% to 24.6% and from 35.7% to 40.0%, respectively. Subjects with high BF%
(>=24% in men, >=34% in women) had higher risk of CVD risk factors in Han (age
adjusted ORs from 1.479 to 3.680, 2.660 to 4.016, respectively). In Mongolia,
adults with high BF% (>=25% in men, >=35% in women) had higher risk of CVD risk
factors (age-adjusted ORs from 2.587 to 3.772, 2.061 to 4.882, respectively).
CONCLUSIONS: The optimal BF% cut-offs for obesity for the prediction of CVD risk
factors in Chinese men and women were approximately 24% and 34% for Han adults
and 25% and 35% for Mongolian population of Inner Mongolia, China, respectively.
PMID- 28420665
TI - Correction.
PMID- 28420664
TI - The UK Cardiac and Vascular Surgery Interventional Anaemia Response (CAVIAR)
Study: protocol for an observational cohort study to determine the impact and
effect of preoperative anaemia management in cardiac and vascular surgical
patients.
AB - INTRODUCTION: Preoperative anaemia is linked to poor postsurgical outcome, longer
hospital stays, greater risk of complications and mortality. Currently in the UK,
some sites have developed anaemia clinics or pathways that use intravenous iron
to correct iron deficiency anaemia prior to surgery as their standard of care.
Although intravenous iron has been observed to be effective in a variety of
patient settings, there is insufficient evidence in its use in cardiac and
vascular patients. The aim of this study is to observe the impact and effect of
anaemia and its management in patients undergoing cardiac and vascular surgery.
In addition, the UK Cardiac and Vascular Surgery Interventional Anaemia Response
(CAVIAR) Study is also a feasibility study with the aim to establish anaemia
management pathways in the preoperative setting to inform the design of future
randomised controlled trials. METHODS AND ANALYSIS: The UK CAVIAR Study is a
multicentre, stepped, observational study, in patients awaiting major cardiac or
vascular surgery. We will be examining different haematological variables
(especially hepcidin), functional capacity and patient outcome. Patients will be
compared based on their anaemia status, whether they received intravenous iron in
accordance to their hospital's preoperative pathway, and their disease group. The
primary outcomes are the change in haemoglobin levels from baseline (before
treatment) to before surgery; and the number of successful patients recruited and
consented (feasibility). The secondary outcomes will include changes in
biomarkers of iron deficiency, length of stay, quality of life and postoperative
recovery. ETHICS AND DISSEMINATION: The study protocol was approved by the London
Westminster Research Ethics Committee (15/LO/1569, 27 November 2015). NHS
approval was also obtained with each hospital trust. The findings of the study
will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinical
Trials registry (NCT02637102) and the ISRCTN registry (ISRCTN55032357).
PMID- 28420666
TI - Prevalence and Clinical Implication of Double Mutations in Hypertrophic
Cardiomyopathy: Revisiting the Gene-Dose Effect.
AB - BACKGROUND: Available data suggests that double mutations in patients with
hypertrophic cardiomyopathy are not rare and are associated with a more severe
phenotype. Most of this data, however, is based on noncontemporary variant
classification. METHODS AND RESULTS: Clinical data of all hypertrophic
cardiomyopathy patients with 2 rare genetic variants were retrospectively
reviewed and compared with a group of patients with a single disease-causing
variant. Furthermore, a literature search was performed for all studies with
information on prevalence and outcome of patients with double mutations.
Classification of genetic variants was reanalyzed according to current
guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare
variants in sarcomeric genes but only in 1 case (0.4%) were both variants
classified as pathogenic. Patients with 2 rare variants had a trend toward
younger age at presentation when compared with patients with a single mutation.
All other clinical variables were similar. In data pooled from cohort studies in
the literature, 8% of gene-positive patients were published to have double
mutations. However, after reanalysis of reported variants, this prevalence
diminished to 0.4%. All patients with 2 radical mutations in MYBPC3 in the
literature had severe disease with death or heart transplant during the first
year of life. Data on other specific genotype-phenotype correlations were scarce.
CONCLUSIONS: Double mutations in patients with hypertrophic cardiomyopathy are
much less common than previously estimated. With the exception of double radical
MYBPC3 mutations, there is little data to guide clinical decision making in cases
with double mutations.
PMID- 28420667
TI - Are Double Mutations Double Trouble?
PMID- 28420668
TI - Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.
AB - RATIONALE: The liver is the central organ that responds to dietary cholesterol
intake and facilitates the release and clearance of lipoprotein particles.
Persistent hypercholesterolemia leads to immune responses against lipoprotein
particles that drive atherosclerosis. However, the effect of hypercholesterolemia
on hepatic T-cell differentiation remains unknown. OBJECTIVE: To investigate
hepatic T-cell subsets upon hypercholesterolemia. METHODS AND RESULTS: We
observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg)
cell population and increased the expression of transforming growth factor-beta1
in the liver. Adoptive transfer experiments revealed that intrahepatically
differentiated Treg cells relocated to the inflamed aorta in atherosclerosis
prone low-density lipoprotein receptor deficient (Ldlr-/-) mice. Moreover,
hypercholesterolemia induced the differentiation of intrahepatic, but not
intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver
homeostasis in hypercholesterolemic Ldlr-/- mice led to intrahepatic Th1 cell
differentiation and CD11b+CD11c+ leukocyte accumulation. CONCLUSIONS: Our results
elucidate a new mechanism that controls intrahepatic T-cell differentiation
during atherosclerosis development and indicates that intrahepatically
differentiated T cells contribute to the CD4+ T-cell pool in the atherosclerotic
aorta.
PMID- 28420670
TI - Confirmed early myocardial rupture in a patient with pulseless electrical
activity (PEA) following late presentation of ST elevation myocardial infarction.
PMID- 28420669
TI - A Possible Early Biomarker for Bicuspid Aortopathy: Circulating Transforming
Growth Factor beta-1 to Soluble Endoglin Ratio.
AB - RATIONALE: The pathogenesis of bicuspid aortic valve (BAV)-associated aortopathy
is poorly understood, and no prognostic biomarker is currently available.
OBJECTIVE: We aimed to identify putative circulating biomarkers pathogenetically
and prognostically linked to bicuspid aortopathy. METHODS AND RESULTS: By reverse
transcription polymerase chain reaction, we evaluated gene expression variations
(versus normal aorta) of transforming growth factor-beta1 (TGF-beta1), connective
tissue growth factor, matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG),
and superoxide dismutase 3 in ascending aorta samples from 50 tricuspid and 70
patients with BAV undergoing surgery for aortic stenosis (aorta diameter <=45 mm:
BAVnon-dil or >45 mm: BAVdil). Expression changes of the TGF-beta1 active dimer
and ENG were analyzed also by Western blot in ascending aorta samples from other
10 tricuspid aortic valve, 10 BAVnon-dil, and 10 BAVdil patients. The serum
concentration of study targets was assessed through ELISA and the ratio of serum
TGF-beta1/ENG (T/E) was evaluated. All BAVnon-dil patients underwent follow-up
echocardiography to assess aortic growth rate. In BAVnon-dil patients, TGF-beta1
and MMP-2 gene expression increased significantly, whereas MMP-14 and ENG
expression decreased versus controls. Expression changes were confirmed at
protein level for TGF-beta1 and ENG. TGF-beta1 serum concentration significantly
decreased in tricuspid aortic valve and BAVnon-dil patients versus healthy
subjects. ENG serum concentration decreased in all patients, more markedly in
BAVdil. A significant increase of the T/E ratio versus healthy subjects was
unique of patients with BAV. In BAVnon-dil patients, a T/E >=9 was independently
associated in multivariable analysis with higher MMP-2 and lower superoxide
dismutase 3 gene expression, independent of age and aortic diameter. A
significant correlation was observed between baseline T/E ratio and aortic
diameter growth rate in BAVnon-dil patients (r=0.66, P<0.001). CONCLUSIONS: The
novel evidence of a possible value of the T/E ratio as a biomarker of BAV
aortopathy was presented: further validation studies are warranted.
PMID- 28420671
TI - PTK7 localization and protein stability is affected by canonical Wnt ligands.
AB - Protein tyrosine kinase 7 (PTK7) is an evolutionarily conserved transmembrane
receptor with important roles in embryonic development and disease. Originally
identified as a gene upregulated in colon cancer, it was later shown to regulate
planar cell polarity (PCP) and directional cell movement. PTK7 is a Wnt co
receptor; however, its role in Wnt signaling remains controversial. Here, we find
evidence that places PTK7 at the intersection of canonical and non-canonical Wnt
signaling pathways. In presence of canonical Wnt ligands PTK7 is subject to
caveolin-mediated endocytosis, while it is unaffected by non-canonical Wnt
ligands. PTK7 endocytosis is dependent on the presence of the PTK7 co-receptor
Fz7 (also known as Fzd7) and results in lysosomal degradation of PTK7. As we
previously observed that PTK7 activates non-canonical PCP Wnt signaling but
inhibits canonical Wnt signaling, our data suggest a mutual inhibition of
canonical and PTK7 Wnt signaling. PTK7 likely suppresses canonical Wnt signaling
by binding canonical Wnt ligands thereby preventing their interaction with Wnt
receptors that would otherwise support canonical Wnt signaling. Conversely, if
canonical Wnt proteins interact with the PTK7 receptor, they induce its
internalization and degradation.
PMID- 28420672
TI - 3D motion of vesicles along microtubules helps them to circumvent obstacles in
cells.
AB - Vesicle transport is regulated at multiple levels, including regulation by
scaffolding proteins and the cytoskeleton. This tight regulation is essential,
since slowing or stoppage of transport can cause accumulation of obstacles and
has been linked to diseases. Understanding the mechanisms by which transport is
regulated as well as how motor proteins overcome obstacles can give important
clues as to how these mechanisms break down in disease states. Here, we describe
that the cytoskeleton architecture impacts transport in a vesicle-size-dependent
manner, leading to pausing of vesicles larger than the separation of the
microtubules. We further develop methods capable of following 3D transport
processes in living cells. Using these methods, we show that vesicles move using
two different modes along the microtubule. Off-axis motion, which leads to
repositioning of the vesicle in 3D along the microtubule, correlates with the
presence of steric obstacles and may help in circumventing them.
PMID- 28420673
TI - A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent
Hypoglycemia in Patients With Type 1 Diabetes.
AB - High-intensity interval training (HIIT) has gained increasing popularity in
patients with diabetes. HIIT acutely increases plasma lactate levels. This may be
important, since the administration of lactate during hypoglycemia suppresses
symptoms and counterregulation while preserving cognitive function. We tested the
hypothesis that, in the short term, HIIT reduces awareness of hypoglycemia and
attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover
trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH),
patients with impaired awareness of hypoglycemia (IAH), and healthy participants
(n = 10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp,
either after a HIIT session or after seated rest. Compared with rest, HIIT
reduced symptoms of hypoglycemia in patients with NAH but not in healthy
participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive
dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT
suppressed cortisol and growth hormone responses, but not catecholamine responses
to hypoglycemia. The present findings demonstrate that a single HIIT session
rapidly reduces awareness of subsequent hypoglycemia in patients with type 1
diabetes and NAH, but does not in patients with IAH, and attenuates hypoglycemia
induced cognitive dysfunction. The role of exercise-induced lactate in mediating
these effects, potentially serving as an alternative fuel for the brain, should
be further explored.
PMID- 28420674
TI - Indian surgeons call for end to unnecessary operations in private sector.
PMID- 28420676
TI - The association between etanercept serum concentration and psoriasis severity is
highly age-dependent.
AB - The association between etanercept serum concentration and psoriasis disease
severity is poorly investigated, and currently etanercept serum concentration
monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In
this prospective study, we investigated the relation between etanercept exposure
and disease severity via measuring etanercept concentrations at five consecutive
time points in 56 psoriasis patients. Disease severity assessments included the
Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician
Global Assessment (PGA), and etanercept and anti-etanercept antibody
concentrations were determined every 3 months for a period of 1 year. The present
study demonstrated that the association between etanercept concentration and
psoriasis severity is age-dependent: when patients were stratified into three
groups, patients in the youngest age group (-50 years) showed a lower PASI at a
higher etanercept concentration (beta = -0.26), whereas patients in the oldest
age group (+59 years) showed the opposite trend (beta =0.22). Similar age effects
were observed in the relation of etanercept concentration with BSA (P=0.02) and
PGA (P=0.02). The influence of age and length of time in therapy on the
etanercept concentration-disease severity relation was unaffected by body mass
index (BMI) or any other possible confounder. Incidence of anti-etanercept
antibodies was low (2%). The age-dependent relation between etanercept serum
concentrations is both unexpected and intriguing and needs further investigation.
PMID- 28420675
TI - Integrative analysis unveils new functions for the Drosophila Cutoff protein in
noncoding RNA biogenesis and gene regulation.
AB - Piwi-interacting RNAs (piRNAs) are central components of the piRNA pathway, which
directs transposon silencing and guarantees genome integrity in the germ cells of
several metazoans. In Drosophila, piRNAs are produced from discrete regions of
the genome termed piRNA clusters, whose expression relies on the RDC complex
comprised of the core proteins Rhino, Deadlock, and Cutoff. To date, the RDC
complex has been exclusively implicated in the regulation of the piRNA loci. Here
we further elucidate the function of Cutoff and the RDC complex by performing
genome-wide ChIP-seq and RNA-seq assays in the Drosophila ovaries and analyzing
these data together with other publicly available data sets. In agreement with
previous studies, we confirm that Cutoff is involved in the transcriptional
regulation of piRNA clusters and in the repression of transposable elements in
germ cells. Surprisingly, however, we find that Cutoff is enriched at and affects
the expression of other noncoding RNAs, including spliceosomal RNAs (snRNAs) and
small nucleolar RNAs (snoRNAs). At least in some instances, Cutoff appears to act
at a transcriptional level in concert with Rhino and perhaps Deadlock. Finally,
we show that mutations in Cutoff result in the deregulation of hundreds of
protein-coding genes in germ cells. Our study uncovers a broader function for the
RDC complex in the Drosophila germline development.
PMID- 28420677
TI - Typing and Characterization of Bacteria Using Bottom-up Tandem Mass Spectrometry
Proteomics.
AB - Methods for rapid and reliable microbial identification are essential in modern
healthcare. The ability to detect and correctly identify pathogenic species and
their resistance phenotype is necessary for accurate diagnosis and efficient
treatment of infectious diseases. Bottom-up tandem mass spectrometry (MS)
proteomics enables rapid characterization of large parts of the expressed genes
of microorganisms. However, the generated data are highly fragmented, making
downstream analyses complex. Here we present TCUP, a new computational method for
typing and characterizing bacteria using proteomics data from bottom-up tandem
MS. TCUP compares the generated protein sequence data to reference databases and
automatically finds peptides suitable for characterization of taxonomic
composition and identification of expressed antimicrobial resistance genes. TCUP
was evaluated using several clinically relevant bacterial species (Escherichia
coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae,
Moraxella catarrhalis, and Haemophilus influenzae), using both simulated data
generated by in silico peptide digestion and experimental proteomics data
generated by liquid chromatography-tandem mass spectrometry (MS/MS). The results
showed that TCUP performs correct peptide classifications at rates between 90.3
and 98.5% at the species level. The method was also able to estimate the relative
abundances of individual species in mixed cultures. Furthermore, TCUP could
identify expressed beta-lactamases in an extended spectrum beta-lactamase
producing (ESBL) E. coli strain, even when the strain was cultivated in the
absence of antibiotics. Finally, TCUP is computationally efficient, easy to
integrate in existing bioinformatics workflows, and freely available under an
open source license for both Windows and Linux environments.
PMID- 28420678
TI - Automated analysis of high-content microscopy data with deep learning.
AB - Existing computational pipelines for quantitative analysis of high-content
microscopy data rely on traditional machine learning approaches that fail to
accurately classify more than a single dataset without substantial tuning and
training, requiring extensive analysis. Here, we demonstrate that the application
of deep learning to biological image data can overcome the pitfalls associated
with conventional machine learning classifiers. Using a deep convolutional neural
network (DeepLoc) to analyze yeast cell images, we show improved performance over
traditional approaches in the automated classification of protein subcellular
localization. We also demonstrate the ability of DeepLoc to classify highly
divergent image sets, including images of pheromone-arrested cells with abnormal
cellular morphology, as well as images generated in different genetic backgrounds
and in different laboratories. We offer an open-source implementation that
enables updating DeepLoc on new microscopy datasets. This study highlights deep
learning as an important tool for the expedited analysis of high-content
microscopy data.
PMID- 28420679
TI - Tumor Microenvironment Targeting and Responsive Peptide-Based Nanoformulations
for Improved Tumor Therapy.
AB - The tumor microenvironment participates in all stages of tumor progression and
has emerged as a promising therapeutic target for cancer therapy. Rapid progress
in the field of molecular self-assembly using various biologic molecules has
resulted in the fabrication of nanoformulations that specifically target and
regulate microenvironment components to inhibit tumor growth. This inhibition
process is based on differentiating between biophysicochemical cues guiding tumor
and normal tissue microenvironments. Peptides and peptide derivatives, owing to
their biocompatibility, chemical versatility, bioactivity, environmental
sensitivity, and biologic recognition abilities, have been widely used as
building blocks to construct multifunctional nanostructures for targeted drug
delivery and controlled release. Several groups of peptides have been identified
as having the ability to penetrate plasma membranes, regulate the essential
signaling pathways of angiogenesis and immune reactions, and recognize key
components in the tumor microenvironment (such as vascular systems, stromal
cells, and abnormal tumor biophysicochemical features). Thus, using different
modules, various functional peptides, and their derivatives can be integrated
into nanoformulations specifically targeting the tumor microenvironment with
increased selectivity, on-demand response, elevated cellular uptake, and improved
tumor therapy. In this review, we introduce several groups of functional peptides
and highlight peptide-based nanoformulations that specifically target the tumor
microenvironment. We also provide our perspective on the development of smart
drug-delivery systems with enhanced therapeutic efficacy.
PMID- 28420681
TI - Mumps in a 27-year-old man.
PMID- 28420680
TI - Use of azithromycin and risk of ventricular arrhythmia.
AB - BACKGROUND: There are conflicting findings from observational studies of the
arrhythrogenic potential of azithromycin. Our aim was to quantify the association
between azithromycin use and the risk of ventricular arrhythmia. METHODS: We
conducted a nested case-control study within a cohort of new antibiotic users
identified from a network of 7 population-based health care databases in Denmark,
Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010.
Up to 100 controls per case were selected and matched by age, sex and database.
Recency of antibiotic use and type of drug (azithromycin was the exposure of
interest) at the index date (occurrence of ventricular arrhythmia) were
identified. We estimated the odds of ventricular arrhythmia associated with
current azithromycin use relative to current amoxicillin use or nonuse of
antibiotics (>= 365 d without antibiotic exposure) using conditional logistic
regression, adjusting for confounders. RESULTS: We identified 14 040 688 new
antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed
in 12 874, of whom 30 were current azithromycin users. The mean age of the cases
and controls was 63 years, and two-thirds were male. In the pooled data analyses
across databases, azithromycin use was associated with an increased risk of
ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio
[OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk
disappeared when current amoxicillin use was the comparator (adjusted OR 0.90,
95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed
results from the pooled data analysis. INTERPRETATION: Current azithromycin use
was associated with an increased risk of ventricular arrhythmia when compared
with nonuse of antibiotics, but not when compared with current amoxicillin use.
The decreased risk with an active comparator suggests significant confounding by
indication.
PMID- 28420682
TI - Bamboo nodes of the vocal cords.
PMID- 28420683
TI - Hot bodies; Cold War: the forgotten history of breast thermography.
PMID- 28420684
TI - Snowfall and myocardial infarction. What is the effect of barometric pressure?
PMID- 28420685
TI - Response to: "Snowfall and myocardial infarction. What is the effect of
barometric pressure?"
PMID- 28420686
TI - Canada wins legal battle to set patent rules.
PMID- 28420687
TI - Home visits to frail elderly can save money and angst.
PMID- 28420688
TI - Can a partnership between general practitioners and ambulance services reduce
conveyance to emergency care?
AB - BACKGROUND: Emergency services are facing increasing workload pressures, and new
models of care are needed. We evaluate the impact of a service development
involving a partnership between emergency ambulance crews and general
practitioners (GPs) on reducing conveyance rates to the Hospital Emergency
Department(ED) . METHODS: The service model was implemented in the West Midlands
of England. Call handlers identified patients with needs that could be addressed
by a GP using locally agreed criteria. GPs supported the assessment of such
patients either at scene or by telephone. Routine data were collected from
October 2012 to November 2013, from the ambulance service computer-aided dispatch
system. Logistic regression models were used to determine the likelihood for
patients being transported to ED. RESULTS: Of 23 395 emergency contacts during
the evaluation period, 1903 (8.1 %) patients were triaged to GP supported
assessment. Mean age (SD) was 61.8 (27.9) years; 42.9 % were aged 75 years and
over. 1221 (64.2%) had face-to-face GP assessment and 682 (35.8%) via telephone.
1500 (78%) of those who received GP support were not transported to hospital.
After controlling for confounders, those aged greater than 75 years (OR 0.67; 95%
CI 0.52 to 0.86), and females (OR 0.64; 95% CI 0.51 to 0.82) were less likely to
be transported, while those who received GP telephone input rather than face-to
face assessment were more likely to be transferred to an ED (OR 2.14; 95% CI 1.69
to 2.72). CONCLUSION: Support of the paramedic service by GPs enabled patients to
avoid transfer to an ED, potentially avoiding subsequent hospital admission,
reducing costs and improving quality of care for patients that are not in need of
hospital services. However, use of services in the days following the call was
not assessed, and hence the overall impact and safety requires further
evaluation.
PMID- 28420689
TI - 'The year of first aid': effectiveness of a 3-day first aid programme for 7-14
year-old primary school children.
AB - AIM OF THE STUDY: Bystanders can play an important role in the event of sudden
injury or illness. Our aim was to evaluate the effects of a 3-day first aid
course for all primary school age groups (7-14 years old). METHODS: 582 school
children were involved in the study. Training consisted of three sessions with
transfer of theoretical knowledge and practical skills about first aid. The
following most urgent situations were addressed in our study: adult basic life
support (BLS), using an automated external defibrillator (AED), handling an
unconscious patient, managing bleeding and calling the ambulance. Data collection
was made with a questionnaire developed for the study and observation. Students
were tested before, immediately after and 4 months after training. Results were
considered significant in case of p<0.05. RESULTS: Prior to training there was a
low level of knowledge and skills on BLS, management of the unconscious patient,
use of an AED and management of bleeding. Knowledge and skills improved
significantly in all of these categories (p<0.01) and remained significantly
higher than the pre-test level at 4 months after training (p<0.01). Younger
children overall performed less well than older children, but significantly
improved over the pre-test level both immediately and 4 months after training
(p<0.01). Prior first aid training was associated with knowledge of the correct
ambulance number (p=0.015) and management of bleeding (p=0.041). Prior to
training, age was associated with pre-test knowledge and skills of all topics
(p<0.01); after training, it was only associated with AED use (p<0.001). There
was a significant correlation between the depth of chest compression and
children's age, weight, height and body mass index (p<0.001). Ventilation
depended on the same factors (p<0.001). CONCLUSION: Children aged 7-14 years are
able to perform basic life-saving skills. Knowledge retention after 4 months is
good for skills, but thinking in algorithms is difficult for these children.
PMID- 28420690
TI - Identification of protein features encoded by alternative exons using Exon
Ontology.
AB - Transcriptomic genome-wide analyses demonstrate massive variation of alternative
splicing in many physiological and pathological situations. One major challenge
is now to establish the biological contribution of alternative splicing variation
in physiological- or pathological-associated cellular phenotypes. Toward this
end, we developed a computational approach, named "Exon Ontology," based on terms
corresponding to well-characterized protein features organized in an ontology
tree. Exon Ontology is conceptually similar to Gene Ontology-based approaches but
focuses on exon-encoded protein features instead of gene level functional
annotations. Exon Ontology describes the protein features encoded by a selected
list of exons and looks for potential Exon Ontology term enrichment. By applying
this strategy to exons that are differentially spliced between epithelial and
mesenchymal cells and after extensive experimental validation, we demonstrate
that Exon Ontology provides support to discover specific protein features
regulated by alternative splicing. We also show that Exon Ontology helps to
unravel biological processes that depend on suites of coregulated alternative
exons, as we uncovered a role of epithelial cell-enriched splicing factors in the
AKT signaling pathway and of mesenchymal cell-enriched splicing factors in
driving splicing events impacting on autophagy. Freely available on the web, Exon
Ontology is the first computational resource that allows getting a quick insight
into the protein features encoded by alternative exons and investigating whether
coregulated exons contain the same biological information.
PMID- 28420691
TI - Clustering of Drosophila housekeeping promoters facilitates their expression.
AB - Housekeeping genes of animal genomes cluster in the same chromosomal regions. It
has long been suggested that this organization contributes to their steady
expression across all the tissues of the organism. Here, we show that the
activity of Drosophila housekeeping gene promoters depends on the expression of
their neighbors. By measuring the expression of ~85,000 reporters integrated in
Kc167 cells, we identified the best predictors of expression as chromosomal
contacts with the promoters and terminators of active genes. Surprisingly, the
chromatin composition at the insertion site and the contacts with enhancers were
less informative. These results are substantiated by the existence of genomic
"paradoxical" domains, rich in euchromatic features and enhancers, but where the
reporters are expressed at low level, concomitant with a deficit of interactions
with promoters and terminators. This indicates that the proper function of
housekeeping genes relies not on contacts with long distance enhancers but on
spatial clustering. Overall, our results suggest that spatial proximity between
genes increases their expression and that the linear architecture of the
Drosophila genome contributes to this effect.
PMID- 28420692
TI - An improved assembly and annotation of the allohexaploid wheat genome identifies
complete families of agronomic genes and provides genomic evidence for
chromosomal translocations.
AB - Advances in genome sequencing and assembly technologies are generating many high
quality genome sequences, but assemblies of large, repeat-rich polyploid genomes,
such as that of bread wheat, remain fragmented and incomplete. We have generated
a new wheat whole-genome shotgun sequence assembly using a combination of
optimized data types and an assembly algorithm designed to deal with large and
complex genomes. The new assembly represents >78% of the genome with a scaffold
N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation
combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full
length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156
noncoding RNA genes. We confirmed three known and identified one novel genome
rearrangements. Our approach enables the rapid and scalable assembly of wheat
genomes, the identification of structural variants, and the definition of
complete gene models, all powerful resources for trait analysis and breeding of
this key global crop.
PMID- 28420693
TI - Modulation of innate immunity of patients with Alzheimer's disease by omega-3
fatty acids.
AB - The innate immune system of patients with Alzheimer's disease and mild cognitive
impairment (MCI) is deregulated with highly increased or decreased transcription
of inflammatory genes and consistently depressed phagocytosis of amyloid-beta1-42
(Abeta) by monocytes and macrophages. Current immune therapies target single
mechanisms in the adaptive immune system but not innate immunity. Here, we
summarize recent advances in therapy by omega-3, omega-6, and epoxy fatty acids;
specialized proresolving mediators; and vitamin D3 that have proven immune
effects and emerging cognitive effects in patients with MCI. The hypothesis of
this approach is that macrophages of normal participants, but not those of
patients with Alzheimer's disease and MCI, possess effective phagocytosis for
Abeta and protect homeostasis of the brain and, furthermore, that defective MCI
macrophages recover phagocytic function via omega-3. Recent studies of fish
derived omega-3 supplementation in patients with MCI have shown polarization of
Apoepsilon3/epsilon3 patients' macrophages to an intermediate M1-M2 phenotype
that is optimal for Abeta phagocytosis and the stabilization of cognitive
decline. Therefore, accumulating preclinical and preliminary clinical evidence
indicates that omega-3 supplementation should be tested in a randomized
controlled clinical trial and that the analysis should involve the apolipoprotein
E genotype and intervening conditions during trial.-Fiala, M., Kooij, G., Wagner,
K., Hammock, B., Pellegrini, M. Modulation of innate immunity of patients with
Alzheimer's disease by omega-3 fatty acids.
PMID- 28420695
TI - Adeno-associated virus 9-mediated Cdk5 inhibitory peptide reverses pathologic
changes and behavioral deficits in the Alzheimer's disease mouse model.
AB - Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35,
phosphorylates multiple substrates and plays an essential role in the development
and function of the CNS; however, proteolytic production of p25 from p35 under
stress conditions leads to the inappropriate activation of Cdk5 and contributes
to hyperphosphorylation of tau and other substrates that are related to the
pathogenesis of Alzheimer's disease. Selective inhibition of aberrant Cdk5
activity via genetic overexpression of Cdk5 inhibitory peptide (CIP) reduces
pathologic changes and prevents brain atrophy and memory loss in p25-transgenic
mice. In the present study, we delivered adeno-associated virus 9 carrying green
fluorescent protein-CIP (AAV9-GFP-CIP) to brain cells via intracerebroventricular
infusion in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic 3
mo-old mice after the occurrence of beta-amyloid (Abeta) aggregation and the
hyperphosphorylation of tau. Three months of treatment of AAV9-GFP-CIP reduced
pathologic changes, including tau hyperphosphorylation, (Abeta) deposit,
astrocytosis, and microgliosis, which were correlated with the reversal of memory
loss and anxiety-like behavior observed in APP/PS1 mice. The neuroprotection
effect of AAV9-GFP-CIP lasted an additional 7 mo-the end point of the study.
These findings provide a novel strategy to selectively target Cdk5 for the
treatment of Alzheimer's disease.-He, Y., Pan, S., Xu, M., He, R., Huang, W.,
Song, P., Huang, J., Zhang, H.-T., Hu, Y. Adeno-associated virus 9-mediated Cdk5
inhibitory peptide reverses pathologic changes and behavioral deficits in the
Alzheimer's disease mouse model.
PMID- 28420694
TI - Caffeine preferentially protects against oxygen-induced retinopathy.
AB - Retinopathy of prematurity (ROP) is the leading cause of childhood blindness, but
current anti-VEGF therapy is concerned with delayed retinal vasculature, eye, and
brain development of preterm infants. The clinical observation of reduced ROP
severity in premature infants after caffeine treatment for apnea suggests that
caffeine may protect against ROP. Here, we demonstrate that caffeine did not
interfere with normal retinal vascularization development but selectively
protected against oxygen-induced retinopathy (OIR) in mice. Moreover, caffeine
attenuated not only hypoxia-induced pathologic angiogenesis, but also hyperoxia
induced vaso-obliteration, which suggests a novel protection window by caffeine.
At the hyperoxic phase, caffeine reduced oxygen-induced neural apoptosis by
adenosine A2A receptor (A2AR)-dependent mechanism, as revealed by combined
caffeine and A2AR-knockout treatment. At the hypoxic phase, caffeine reduced
microglial activation and enhanced tip cell formation by A2AR-dependent and
independent mechanisms, as combined caffeine and A2AR knockout produced additive
and nearly full protection against OIR. Together with clinical use of caffeine in
neonates, our demonstration of the selective protection against OIR, effective
therapeutic window, adenosine receptor mechanisms, and neuroglial involvement
provide the direct evidence of the novel effects of caffeine therapy in the
prevention and treatment of ROP.-Zhang, S., Zhou, R., Li, B., Li, H., Wang, Y.,
Gu, X., Tang, L., Wang, C., Zhong, D., Ge, Y., Huo, Y., Lin, J., Liu, X.-L.,
Chen, J.-F. Caffeine preferentially protects against oxygen-induced retinopathy.
PMID- 28420696
TI - Erratum. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin
Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide
Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The
LixiLan-O Randomized Trial. Diabetes Care 2016;39:2026-2035.
PMID- 28420697
TI - Erratum. Sitagliptin Attenuates the Progression of Carotid Intima-Media
Thickening in Insulin-Treated Patients With Type 2 Diabetes: The Sitagliptin
Preventive Study of Intima-Media Thickness Evaluation (SPIKE). A Randomized
Controlled Trial. Diabetes Care 2016;39:455-464.
PMID- 28420698
TI - Erratum. Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist
LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies.
Diabetes Care 2016;39:1241-1249.
PMID- 28420699
TI - Erratum. Alogliptin, a Dipeptidyl Peptidase 4 Inhibitor, Prevents the Progression
of Carotid Atherosclerosis in Patients With Type 2 Diabetes: The Study of
Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A). Diabetes
Care 2016;39:139-148.
PMID- 28420700
TI - Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and
Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear
Factor 1B (HNF1B) Molecular Defects.
AB - OBJECTIVE: Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are
associated with a multiorgan disease, including diabetes (maturity-onset diabetes
of the young 5) and kidney abnormalities. The HNF1B syndrome is related to HNF1B
mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we
described HNF1B-related diabetes and associated phenotypes and assessed
genotype/phenotype correlations at diagnosis and in the long-term. RESEARCH
DESIGN AND METHODS: This multicenter retrospective cohort study included 201
patients, aged 18 years or older at follow-up, with HNF1B mutations (n = 101) or
deletion (n = 100). RESULTS: Diabetes was present in 159 patients. At diagnosis,
clinical symptoms of diabetes were present in 67 of 144 patients and HNF1B renal
disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was
observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with
insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46
of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney
disease stages 3-4 (CKD3-4) in 75 of 169 (44%), and end-stage renal disease
(ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with
HNF1B deletion less often had CKD3-4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P
< 10-4) and in the long term (40 of 78 vs. 71 of 91, P = 0.0003). They were
leaner and more frequently treated with insulin. CONCLUSIONS: In patients with
HNF1B syndrome, diabetes complications, cardiovascular risk factors, CKD3-4, and
ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological
and/or functional kidney disease may help etiological diagnosis.
Genotype/phenotype correlations may have implications for the care and the
prognosis of these patients.
PMID- 28420701
TI - Work of breathing and sleep pattern behavior in COPD. How much oxygen or high
flow nasal cannula?
PMID- 28420702
TI - Muscle damage: Scientific fundamentals.
PMID- 28420703
TI - Corrigendum.
PMID- 28420704
TI - Influence of HDL particles on cell-cholesterol efflux under various pathological
conditions.
AB - It has been reported that low cell-cholesterol efflux capacity (CEC) of HDL is an
independent risk factor for CVD. To better understand CEC regulation, we measured
ABCA1- and scavenger receptor class B type I (SR-BI)-dependent cell-cholesterol
efflux, HDL anti-oxidative capacity, HDL particles, lipids, and inflammatory- and
oxidative-stress markers in 122 subjects with elevated plasma levels of
triglyceride (TG), serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), or
beta-sitosterol and in 146 controls. In controls, there were strong positive
correlations between ABCA1-dependent cholesterol efflux and small prebeta-1
concentrations (R2 = 0.317) and SR-BI-dependent cholesterol efflux and large
(alpha-1 + alpha-2) HDL particle concentrations (R2 = 0.774). In high-TG
patients, both the concentration and the functionality (prebeta-1 concentration
normalized ABCA1 efflux) of prebeta-1 particles were significantly elevated
compared with controls; however, though the concentration of large particles was
significantly decreased, their functionality (large HDL concentration-normalized
SR-BI efflux) was significantly elevated. High levels of SAA or MPO were not
associated with decreased functionality of either the small (prebeta-1) or the
large (alpha-1 + alpha-2) HDL particles. HDL anti-oxidative capacity was
negatively influenced by high plasma beta-sitosterol levels, but not by the
concentrations of HDL particles, TG, SAA, fibrinogen, or MPO. Our data
demonstrate that under certain conditions CEC is influenced not only by
quantitative (concentration), but also by qualitative (functional) properties of
HDL particles.
PMID- 28420705
TI - Synthesis of neutral ether lipid monoalkyl-diacylglycerol by lipid
acyltransferases.
AB - In mammals, ether lipids exert a wide spectrum of signaling and structural
functions, such as stimulation of immune responses, anti-tumor activities, and
enhancement of sperm functions. Abnormal accumulation of monoalkyl-diacylglycerol
(MADAG) was found in Wolman's disease, a human genetic disorder defined by a
deficiency in lysosomal acid lipase. In the current study, we found that among
the nine recombinant human lipid acyltransferases examined, acyl
CoA:diacylglycerol acyltransferase (DGAT)1, DGAT2, acyl-CoA:monoacylglycerol
acyltransferase (MGAT)2, MGAT3, acyl-CoA:wax-alcohol acyltransferase 2/MFAT, and
DGAT candidate 3 were able to use 1-monoalkylglycerol (1-MAkG) as an acyl
acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG). These enzymes
demonstrated different enzymatic turnover rates and relative efficiencies for the
first and second acylation steps leading to the synthesis of MAMAG and MADAG,
respectively. They also exhibited different degrees of substrate preference when
presented with 1-monooleoylglycerol versus 1-MAkG. In CHO-K1 cells, treatment
with DGAT1 selective inhibitor, XP-620, completely blocked the synthesis of
MADAG, indicating that DGAT1 is the predominant enzyme responsible for the
intracellular synthesis of MADAG in this model system. The levels of MADAG in the
adrenal gland of DGAT1 KO mice were reduced as compared with those of the WT
mice, suggesting that DGAT1 is a major enzyme for the synthesis of MADAG in this
tissue. Our findings indicate that several of these lipid acyltransferases may be
able to synthesize neutral ether lipids in mammals.
PMID- 28420707
TI - Role of the fatty acid-binding protein 4 in heart failure and cardiovascular
disease.
AB - Obesity and ectopic fat accumulation in non-adipose tissues are major
contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes
act as endocrine organs by releasing a large number of bioactive molecules into
the bloodstream, which participate in a communication network between white
adipose tissue and other organs, including the heart. Among these molecules,
fatty acid-binding protein 4 (FABP4) has recently been shown to increase
cardiometabolic risk. Both clinical and experimental evidence have identified
FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it
has been directly related to cardiac alterations such as left ventricular
hypertrophy (LVH) and both systolic and diastolic cardiac dysfunction. The
available interventional studies preclude the establishment of a direct causal
role of this molecule in CVD and HF and propose FABP4 as a biomarker rather than
as an aetiological factor. However, several experimental reports have suggested
that FABP4 may act as a direct contributor to cardiac metabolism and
physiopathology, and the pharmacological targeting of FABP4 may restore some of
the metabolic alterations that are conducive to CVD and HF. Here, we review the
current knowledge regarding FABP4 in the context of HF and CVD as well as the
molecular basis by which this protein participates in the regulation of cardiac
function.
PMID- 28420706
TI - Common structural features of cholesterol binding sites in crystallized soluble
proteins.
AB - Cholesterol-protein interactions are essential for the architectural organization
of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in
transmembrane proteins have been identified, little is known about cholesterol
recognition by soluble proteins. We reviewed the structural characteristics of
binding sites for cholesterol and cholesterol sulfate from crystallographic
structures available in the Protein Data Bank. This analysis unveiled key
features of cholesterol-binding sites that are present in either all or the
majority of sites: i) the cholesterol molecule is generally positioned between
protein domains that have an organized secondary structure; ii) the cholesterol
hydroxyl/sulfo group is often partnered by Asn, Gln, and/or Tyr, while the
hydrophobic part of cholesterol interacts with Leu, Ile, Val, and/or Phe; iii)
cholesterol hydrogen-bonding partners are often found on alpha-helices, while
amino acids that interact with cholesterol's hydrophobic core have a slight
preference for beta-strands and secondary structure-lacking protein areas; iv)
the steroid's C21 and C26 constitute the "hot spots" most often seen for steroid
protein hydrophobic interactions; v) common "cold spots" are C8-C10, C13, and
C17, at which contacts with the proteins were not detected. Several common
features we identified for soluble protein-steroid interaction appear
evolutionarily conserved.
PMID- 28420708
TI - Activation of the P2Y2 receptor regulates bone cell function by enhancing ATP
release.
AB - Bone cells constitutively release ATP into the extracellular environment where it
acts locally via P2 receptors to regulate bone cell function. Whilst P2Y2
receptor stimulation regulates bone mineralisation, the functional effects of
this receptor in osteoclasts remain unknown. This investigation used the P2Y2
receptor knockout (P2Y2R-/- ) mouse model to investigate the role of this
receptor in bone. MicroCT analysis of P2Y2R-/- mice demonstrated age-related
increases in trabecular bone volume (<=48%), number (<=30%) and thickness
(<=17%). In vitro P2Y2R-/- osteoblasts displayed a 3-fold increase in bone
formation and alkaline phosphatase activity, whilst P2Y2R-/- osteoclasts
exhibited a 65% reduction in resorptive activity. Serum cross-linked C
telopeptide levels (CTX, resorption marker) were also decreased (<=35%). The
resorption defect in P2Y2R-/- osteoclasts was rescued by the addition of
exogenous ATP, suggesting that an ATP deficit could be a key factor in the
reduced function of these cells. In agreement, we found that basal ATP release
was reduced up to 53% in P2Y2R-/- osteoclasts. The P2Y2 receptor agonists, UTP
and 2-thioUTP, increased osteoclast activity and ATP release in wild-type but not
in P2Y2R-/- cells. This indicates that the P2Y2 receptor may regulate osteoclast
function indirectly by promoting ATP release. UTP and 2-thioUTP also stimulate
ATP release from osteoblasts suggesting that the P2Y2 receptor exerts a similar
function in these cells. Taken together, our findings are consistent with the
notion that the primary action of P2Y2 receptor signalling in bone is to regulate
extracellular ATP levels.
PMID- 28420709
TI - Thermal imprinting modifies adult stress and innate immune responsiveness in the
teleost sea bream.
AB - The impact of thermal imprinting on the plasticity of the hypothalamic-pituitary
interrenal (HPI) axis and stress response in an adult ectotherm, the gilthead sea
bream (Sparusaurata, L.), during its development was assessed. Fish were reared
under 4 thermal regimes, and the resulting adults exposed to acute confinement
stress and plasma cortisol levels and genes of the HPI axis were monitored.
Changes in immune function, a common result of stress, were also evaluated using
histomorphometric measurements of melanomacrophages centers (MMCs) in the head
kidney and by monitoring macrophage-related transcripts. Thermal history
significantly modified the HPI responsiveness in adult sea bream when eggs and
larvae were reared at a higher than optimal temperature (HT, 22 degrees C), and
they had a reduced amplitude in their cortisol response and significantly
upregulated pituitary pomc and head kidney star transcripts. Additionally, after
an acute stress challenge, immune function was modified and the head kidney of
adult fish reared during development at high temperatures (HT and LHT, 18-22
degrees C) had a decreased number of MMCs and a significant downregulation of
dopachrome tautomerase. Thermal imprinting during development influenced adult
sea bream physiology and increased plasma levels of glucose and sodium even in
the absence of an acute stress in fish reared under a high-low thermal regime
(HLT, 22-18 degrees C). Overall, the results demonstrate that temperature during
early development influences the adult HPI axis and immune function in a teleost
fish.
PMID- 28420710
TI - Reciprocal proteasome-mediated degradation of PIFs and HFR1 underlies
photomorphogenic development in Arabidopsis.
AB - The phytochrome-mediated regulation of photomorphogenesis under red and far-red
light conditions involves both positively and negatively acting factors. The
positively acting factors (e.g. HY5/HFR1/LAF1 and others) are degraded in the
dark to prevent photomorphogenesis. By contrast, the negatively acting factors
(e.g. phytochrome-interacting factors or PIFs) are degraded in response to light
to promote photomorphogenesis. Here, we show that the negatively acting factor
PIF1 is also degraded in the dark by direct heterodimerization with the
positively acting factor HFR1. Conversely, PIF1 also promotes the degradation of
HFR1 in darkness. PIF1 enhances the poly-ubiquitylation of HFR1 by COP1 in vivo
and in vitro In addition, the reciprocal co-degradation of PIF1 and HFR1 is
dependent on the 26S proteasome pathway in vivo Genetic evidence shows that the
hfr1 mutant partially suppresses the constitutive photomorphogenic phenotypes of
cop1-6 pif1 and of the quadruple mutant pifq both in the dark and in far-red
light conditions. Taken together, these data uncover a co-degradation mechanism
between PIFs and HFR1 that underlies photomorphogenic development in Arabidopsis
thaliana.
PMID- 28420711
TI - Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor
circuit.
AB - Establishing and maintaining the appropriate number of GABA synapses is key for
balancing excitation and inhibition in the nervous system, though we have only a
limited understanding of the mechanisms controlling GABA circuit connectivity.
Here, we show that disrupting cholinergic innervation of GABAergic neurons in the
C. elegans motor circuit alters GABAergic neuron synaptic connectivity. These
changes are accompanied by reduced frequency and increased amplitude of GABAergic
synaptic events. Acute genetic disruption in early development, during the
integration of post-embryonic-born GABAergic neurons into the circuit, produces
irreversible effects on GABAergic synaptic connectivity that mimic those produced
by chronic manipulations. In contrast, acute genetic disruption of cholinergic
signaling in the adult circuit does not reproduce these effects. Our findings
reveal that GABAergic signaling is regulated by cholinergic neuronal activity,
probably through distinct mechanisms in the developing and mature nervous system.
PMID- 28420712
TI - Sec71 functions as a GEF for the small GTPase Arf1 to govern dendrite pruning of
Drosophila sensory neurons.
AB - Pruning, whereby neurons eliminate their excess neurites, is central for the
maturation of the nervous system. In Drosophila, sensory neurons, ddaCs,
selectively prune their larval dendrites without affecting their axons during
metamorphosis. However, it is unknown whether the secretory pathway plays a role
in dendrite pruning. Here, we show that the small GTPase Arf1, an important
regulator of the secretory pathway, is specifically required for dendrite pruning
of ddaC/D/E sensory neurons but dispensable for apoptosis of ddaF neurons.
Analyses of the GTP- and GDP-locked forms of Arf1 indicate that the cycling of
Arf1 between GDP-bound and GTP-bound forms is essential for dendrite pruning. We
further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that
preferentially interacts with its GDP-bound form. Like Arf1, Sec71 is also
important for dendrite pruning, but not for apoptosis, of sensory neurons. Arf1
and Sec71 are interdependent for their localizations on Golgi. Finally, we show
that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5
dependent endocytosis to facilitate endocytosis and degradation of the cell
adhesion molecule Neuroglian (Nrg).
PMID- 28420713
TI - Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA.
AB - The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and
glucose metabolism that plays a critical role in energy homeostasis. The impact
of diet on PKA signaling has not been defined, although perturbations in
individual PKA subunits are associated with changes in adiposity, physical
activity and energy intake in mice and humans. We hypothesized that a high fat
diet (HFD) would elicit peripheral and central alterations in the PKA system that
would differ depending on length of exposure to HFD; these differences could
protect against or promote diet-induced obesity (DIO). 12-week-old C57Bl/6J mice
were randomly assigned to a regular diet or HFD and weighed weekly throughout the
feeding studies (4 days, 14 weeks; respectively), and during killing. PKA
activity and subunit expression were measured in liver, gonadal adipose tissue
(AT) and brain. Acute HFD-feeding suppressed basal hepatic PKA activity. In
contrast, hepatic and hypothalamic PKA activities were significantly increased
after chronic HFD-feeding. Changes in AT were more subtle, and overall, altered
PKA regulation in response to chronic HFD exposure was more profound in female
mice. The suppression of hepatic PKA activity after 4 day HFD-feeding was
indicative of a protective peripheral effect against obesity in the context of
overnutrition. In response to chronic HFD-feeding, and with the development of
DIO, dysregulated hepatic and hypothalamic PKA signaling was a signature of
obesity that is likely to promote further metabolic dysfunction in mice.
PMID- 28420715
TI - Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic
nephropathy.
AB - Diabetic nephropathy is one of the most frequent, devastating and costly
complications of diabetes. The available therapeutic approaches are limited.
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose
lowering drugs that might also have reno-protective properties. DPP-4 exists in
two forms: a plasma membrane-bound form and a soluble form, and can exert many
biological actions mainly through its peptidase activity and interaction with
extracellular matrix components. The kidneys have the highest DPP-4 expression
level in mammalians. DPP-4 expression and urinary activity are up-regulated in
diabetic nephropathy, highlighting its role as a potential target to manage
diabetic nephropathy. Preclinical animal studies and some clinical data suggest
that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood
pressure- and glucose-independent manner. Many studies reported that these reno
protective effects could be due to increased half-life of DPP-4 substrates such
as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a).
However, the underlying mechanisms are far from being completely understood and
clearly need further investigations.
PMID- 28420714
TI - Pancreatic islet inflammation: an emerging role for chemokines.
AB - Both type 1 and type 2 diabetes exhibit features of inflammation associated with
alterations in pancreatic islet function and mass. These immunological
disruptions, if unresolved, contribute to the overall pathogenesis of disease
onset. This review presents the emerging role of pancreatic islet chemokine
production as a critical factor regulating immune cell entry into pancreatic
tissue as well as an important facilitator of changes in tissue resident
leukocyte activity. Signaling through two specific chemokine receptors (i.e.,
CXCR2 and CXCR3) is presented to illustrate key points regarding ligand-mediated
regulation of innate and adaptive immune cell responses. The prospective roles of
chemokine ligands and their corresponding chemokine receptors to influence the
onset and progression of autoimmune- and obesity-associated forms of diabetes are
discussed.
PMID- 28420716
TI - A MEN1 pancreatic neuroendocrine tumour mouse model under temporal control.
AB - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder
characterised by occurrence of parathyroid tumours and neuroendocrine tumours
(NETs) of the pancreatic islets and anterior pituitary. The MEN1 gene, encoding
menin, is a tumour suppressor, but its precise role in initiating in vivo
tumourigenesis remains to be elucidated. The availability of a temporally
controlled conditional MEN1 mouse model would greatly facilitate the study of
such early tumourigenic events, and overcome the limitations of other MEN1
knockout models, in which menin is lost from conception or tumour development
occurs asynchronously. To generate a temporally controlled conditional mouse
model, we crossbred mice with the MEN1 gene floxed by LoxP sites (Men1L/L ), and
mice expressing tamoxifen-inducible Cre recombinase under the control of the rat
insulin promoter (RIP2-CreER), to establish a pancreatic beta-cell-specific NET
model under temporal control (Men1L/L /RIP2-CreER). Men1L/L /RIP2-CreER mice aged
~3 months were given tamoxifen in the diet for 5 days, and pancreata harvested 2
2.5, 2.9-3.5 and 4.5-5.5 months later. Control mice did not express Cre and did
not receive tamoxifen. Immunostaining of pancreata from tamoxifen-treated Men1L/L
/RIP2-CreER mice, compared to control mice, showed at all ages: loss of menin in
all islets; increased islet area (>4.2-fold); increased proliferation of insulin
immunostaining beta-cells (>2.3-fold) and decreased proliferation of glucagon
immunostaining alpha-cells (>1.7-fold). There were no gender and apoptotic or
proliferation differences, and extra-pancreatic tumours were not detected. Thus,
we have established a mouse model (Men1L/L /RIP2-CreER) to study early events in
the development of pancreatic beta-cell NETs.
PMID- 28420717
TI - Heart, lipids and hormones.
AB - Cardiovascular disease is the leading cause of death in general population.
Besides well-known risk factors such as hypertension, impaired glucose tolerance
and dyslipidemia, growing evidence suggests that hormonal changes in various
endocrine diseases also impact the cardiac morphology and function. Recent
studies highlight the importance of ectopic intracellular myocardial and
pericardial lipid deposition, since even slight changes of these fat depots are
associated with alterations in cardiac performance. In this review, we overview
the effects of hormones, including insulin, thyroid hormones, growth hormone and
cortisol, on heart function, focusing on their impact on myocardial lipid
metabolism, cardiac substrate utilization and ectopic lipid deposition, in order
to highlight the important role of even subtle hormonal changes for heart
function in various endocrine and metabolic diseases.
PMID- 28420718
TI - Sex, BMI and age differences in metabolic syndrome: the Dutch Lifelines Cohort
Study.
AB - INTRODUCTION: To evaluate the prevalence of metabolic syndrome (MetS) and its
individual components within sex-, body mass index (BMI)- and age combined
clusters. In addition, we used the age-adjusted blood pressure thresholds to
demonstrate the effect on the prevalence of MetS and elevated blood pressure.
SUBJECTS AND METHODS: Cross-sectional data from 74,531 Western European
participants, aged 18-79 years, were used from the Dutch Lifelines Cohort Study.
MetS was defined according to the revised NCEP-ATPIII. Age-adjusted blood
pressure thresholds were defined as recommended by the eight reports of the Joint
National Committee (>=140/90 mmHg for those aged <60 years, and >=150/90 mmHg for
those aged >=60 years). RESULTS: 19.2% men and 12.1% women had MetS. MetS
prevalence increased with BMI and age. Independent of BMI, abdominal obesity
dominated MetS prevalence especially in women, while elevated blood pressure was
already highly prevalent among young men. Applying age-adjusted blood pressure
thresholds resulted in a 0.2-11.9% prevalence drop in MetS and 6.0-36.3%
prevalence drop in elevated blood pressure, within the combined sex, BMI and age
clusters. CONCLUSIONS: We observed a gender disparity with age and BMI for the
prevalence of MetS and, especially, abdominal obesity and elevated blood
pressure. The strict threshold level for elevated blood pressure in the revised
NCEP-ATPIII, results in an overestimation of MetS prevalence.
PMID- 28420720
TI - A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in
Patients with Advanced Solid Tumors.
AB - Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating
the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). This phase
I study investigated the safety, pharmacokinetics, pharmacodynamics, and
antitumor activity of ABC294640, a first-in-class orally available inhibitor of
SK2.Experimental Design: Escalating doses of ABC294640 were administered orally
to patients with advanced solid tumors in sequential cohorts at the following
dose levels: 250 mg qd, 250 mg bid, 500 mg bid, and 750 mg bid, continuously in
cycles of 28 days. Serial blood samples were obtained to measure ABC294640
concentrations and sphingolipid profiles.Results: Twenty-two patients were
enrolled, and 21 received ABC294640. The most common drug-related toxicities were
nausea, vomiting, and fatigue. Among the 4 patients at 750 mg bid, one had dose
limiting grade 3 nausea and vomiting, and 2 were unable to complete cycle 1 due
to diverse drug-related toxicities. The 500 mg bid dose level was established as
the recommended phase II dose. ABC294640 administration resulted in decreases in
S1P levels over the first 12 hours, with return to baseline at 24 hours. The best
response was a partial response in a patient with cholangiocarcinoma at 250 mg
qd, and stable disease was observed in 6 patients with various solid tumors
across dose levels.Conclusions: At 500 mg bid, ABC294640 is well tolerated and
achieves biologically relevant plasma concentrations. Changes in plasma
sphingolipid levels may provide a useful pharmacodynamic biomarker for ABC294640.
Clin Cancer Res; 23(16); 4642-50. (c)2017 AACR.
PMID- 28420721
TI - Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or
Refractory Hematologic Malignancies: A California Cancer Consortium Trial.
AB - Purpose: A phase I study was conducted to determine the MTD, dose-limiting
toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous
emulsion in relapsed/refractory hematologic malignancies.Experimental Design:
Fenretinide (80-1,810 mg/m2/day) was administered by continuous infusion on days
1 to 5, in 21-day cycles, using an accelerated titration design.Results: Twenty
nine patients, treated with a median of three prior regimens (range, 1-7), were
enrolled and received the test drug. Ninety-seven courses were completed. An MTD
was reached at 1,280 mg/m2/day for 5 days. Course 1 DLTs included 6 patients with
hypertriglyceridemia, 4 of whom were asymptomatic; 2 patients experienced DLT
thrombocytopenia (asymptomatic). Of 11 patients with response-evaluable
peripheral T-cell lymphomas, two had complete responses [CR, progression-free
survival (PFS) 68+ months; unconfirmed CR, PFS 14+ months], two had unconfirmed
partial responses (unconfirmed PR, PFS 5 months; unconfirmed PR, PFS 6 months),
and five had stable disease (2-12 cycles). One patient with mature B-cell
lymphoma had an unconfirmed PR sustained for two cycles. Steady-state plasma
levels were approximately 10 mcg/mL (mid-20s MUmol/L) at 640 mg/m2/day,
approximately 14 mcg/mL (mid-30s MUmol/L) at 905 mg/m2/day, and approximately 22
mcg/mL (mid-50s MUmol/L) at 1,280 mg/m2/day.Conclusions: Intravenous fenretinide
obtained significantly higher plasma levels than a previous capsule formulation,
had acceptable toxicities, and evidenced antitumor activity in peripheral T-cell
lymphomas. A recommended phase II dosing is 600 mg/m2 on day 1, followed by 1,200
mg/m2 on days 2 to 5, every 21 days. A registration-enabling phase II study in
relapsed/refractory PTCL (ClinicalTrials.gov identifier: NCT02495415) is ongoing.
Clin Cancer Res; 23(16); 4550-5. (c)2017 AACR.
PMID- 28420722
TI - Low Tumor Mitochondrial DNA Content Is Associated with Better Outcome in Breast
Cancer Patients Receiving Anthracycline-Based Chemotherapy.
AB - Purpose: In this study, we aimed to explore whether low levels of mitochondrial
DNA (mtDNA) content in the primary tumor could predict better outcome for breast
cancer patients receiving anthracycline-based therapies. We hypothesized that
tumor cells with low mtDNA content are more susceptible to mitochondrial damage
induced by anthracyclines, and thus are more susceptible to anthracycline
treatment.Experimental Design: We measured mtDNA content by a qPCR approach in
295 primary breast tumor specimens originating from two well-defined cohorts: 174
lymph node-positive patients who received adjuvant chemotherapy and 121 patients
with advanced disease who received chemotherapy as first-line palliative
treatment. The chemotherapy regimens given were either anthracycline-based
(FAC/FEC) or methotrexate-based (CMF).Results: In both the adjuvant and advanced
settings, we observed increased benefit for patients with low mtDNA content in
their primary tumor, but only when treated with FAC/FEC. In multivariable Cox
regression analysis for respectively distant metastasis-free survival and
progression-free survival, the HR for the FAC/FEC-treated mtDNA low group in the
adjuvant setting was 0.46 [95% confidence interval (CI), 0.24-0.89; P = 0.020]
and in the advanced setting 0.49 (95% CI, 0.27-0.90; P = 0.022) compared with the
FAC/FEC-treated mtDNA high group. We did not observe these associations in the
patients treated with CMF.Conclusions: In our two study cohorts, breast cancer
patients with low mtDNA content in their primary tumor had better outcome from
anthracycline-containing chemotherapy. The frequently observed decrease in mtDNA
content in primary breast tumors may be exploited by guiding chemotherapeutic
regimen decision making. Clin Cancer Res; 23(16); 4735-43. (c)2017 AACR.
PMID- 28420719
TI - Emotional Modulation of Learning and Memory: Pharmacological Implications.
AB - Memory consolidation involves the process by which newly acquired information
becomes stored in a long-lasting fashion. Evidence acquired over the past several
decades, especially from studies using post-training drug administration,
indicates that emotional arousal during the consolidation period influences and
enhances the strength of the memory and that multiple different chemical
signaling systems participate in this process. The mechanisms underlying the
emotional influences on memory involve the release of stress hormones and
activation of the basolateral amygdala, which work together to modulate memory
consolidation. Moreover, work suggests that this amygdala-based memory modulation
occurs with numerous types of learning and involves interactions with many
different brain regions to alter consolidation. Additionally, studies suggest
that emotional arousal and amygdala activity in particular influence synaptic
plasticity and associated proteins in downstream brain regions. This review
considers the historical understanding for memory modulation and cellular
consolidation processes and examines several research areas currently using this
foundational knowledge to develop therapeutic treatments.
PMID- 28420723
TI - Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML.
AB - Purpose: Cell-to-cell variability in apoptosis signaling contributes to
heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia,
such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit
mammalian cells to apoptosis and are inhibited by retrotranslocation from the
mitochondria into the cytosol. The subcellular localization of BAX and BAK could
determine the cellular predisposition to apoptotic death.Experimental Design: The
relative localization of BAX and BAK was determined by fractionation of AML cell
lines and patient samples of a test cohort and a validation cohort.Results: This
study shows that relative BAX localization determines the predisposition of
different AML cell lines to apoptosis. Human AML displays a surprising variety of
relative BAX localizations. In a test cohort of 48 patients with AML,
mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD
status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients
treated with myelosuppressive chemotherapy confirmed that relative BAX
localization correlates with probability of disease progression, FLT3-ITD status,
and leukocytosis. Relative BAX localization could therefore be helpful to
identify elderly or frail patients who may benefit from cytotoxic
therapy.Conclusions: In this retrospective analysis of two independent AML
cohorts, our data suggest that Bax localization may predict prognosis of patients
with AML and cellular predisposition to apoptosis, combining the actual
contribution of known and unknown factors to a final "common path." Clin Cancer
Res; 23(16); 4805-16. (c)2017 AACR.
PMID- 28420724
TI - A Zebrafish Model Discovers a Novel Mechanism of Stromal Fibroblast-Mediated
Cancer Metastasis.
AB - Purpose: Cancer metastasis can occur at the early stage of tumor development when
a primary tumor is at the microscopic size. In particular, the interaction of
malignant cells with other cell types including cancer-associated fibroblasts
(CAF) in promoting metastasis at the early stage of tumor development remains
largely unknown. Here, we investigated the role of CAFs in facilitating the
initial events of cancer metastasis when primary tumors were at microscopic
sizes.Experimental Design: Multicolor-coded cancer cells and CAFs were
coimplanted into the transparent zebrafish body and metastasis at a single-cell
level was monitored in living animals. Healthy fibroblasts, tumor factor-educated
fibroblasts, and CAFs isolated from various tumors were tested for their ability
to facilitate metastasis.Results: We showed that CAFs promoted cancer cell
metastasis at the very early stage during primary tumor development. When a
primary tumor was at the microscopic size consisting of a few hundred cells, CAFs
were able to hijack cancer cells for dissemination from the primary site.
Surprisingly, a majority of metastatic cancer cells remained in tight association
with CAFs in the circulation. Furthermore, stimulation of non-metastasis
promoting normal fibroblasts with TGF-B, FGF-2, HGF, and PDGF-BB led to
acquisition of their metastatic capacity.Conclusions: Cancer metastasis occurs at
the very early stage of tumor formation consisting of only a few hundred cells.
CAFs are the key cellular determinant for metastasis. Our findings provide novel
mechanistic insights on CAFs in promoting cancer metastasis and targeting CAFs
for cancer therapy should be aimed at the early stage during cancer development.
Clin Cancer Res; 23(16); 4769-79. (c)2017 AACR.
PMID- 28420725
TI - Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by
Detecting Circulating Tumor DNA in Urine.
AB - Purpose: Noninvasive drug biomarkers for the early assessment of tumor response
can enable adaptive therapeutic decision-making and proof-of-concept studies for
investigational drugs. Circulating tumor DNA (ctDNA) is released into the
circulation by tumor cell turnover and has been shown to be detectable in
urine.Experimental Design: We tested the hypothesis that dynamic changes in EGFR
activating (exon 19del and L858R) and resistance (T790M) mutation levels detected
in urine could inform tumor response within days of therapy for advanced non
small cell lung cancer (NSCLC) patients receiving osimertinib, a second-line
third-generation anti-EGFR tyrosine kinase inhibitor.Results: Eight of nine
evaluable NSCLC patients had detectable T790M-mutant DNA fragments in
pretreatment baseline samples. Daily monitoring of mutations in urine indicated a
pattern of intermittent spikes throughout week 1, suggesting apoptosis with an
overall decrease in fragment numbers from baselines to day 7 preceding
radiographic response assessed at 6 to 12 weeks.Conclusions: These findings
suggest drug-induced tumor apoptosis within days of initial dosing. Daily
sampling of ctDNA may enable early assessment of patient response and proof-of
concept studies for drug development. The modeling of tumor lysis through the day
to-day kinetics of ctDNA released into the blood and then into the urine is
demonstrated in this proof-of-concept study in lung cancer patients receiving
anti-EGFR tyrosine kinase inhibitors. This strategy may determine the specific
clonal populations of cells which undergo apoptosis within the first week of
therapy. This has important implications for developing combinational strategies
to address inter- and intralesional heterogeneity and characterizing residual
disease after initial drug exposure. Clin Cancer Res; 23(16); 4716-23. (c)2017
AACR.
PMID- 28420726
TI - Intra- and Interobserver Reproducibility Assessment of PD-L1 Biomarker in Non
Small Cell Lung Cancer.
AB - Purpose: Reliable and reproducible methods for identifying PD-L1 expression on
tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested
the reproducibility of the assessment of PD-L1 expression in non-small cell lung
cancer (NSCLC) tissue samples by pathologists.Experimental Design: NSCLC samples
were stained with PD-L1 22C3 pharmDx kit using the Dako Autostainer Link 48
Platform. Two sample sets of 60 samples each were designed to assess inter- and
intraobserver reproducibility considering two cut points for positivity: 1% or
50% of PD-L1 stained tumor cells. A randomization process was used to obtain
equal distribution of PD-L1 positive and negative samples within each sample set.
Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all
samples on two consecutive days. Subgroup 2 performed the same assessments,
except they received a 1-hour training session prior to the second
assessment.Results: For intraobserver reproducibility, the overall percent
agreement (OPA) was 89.7% [95% confidence interval (CI), 85.7-92.6] for the 1%
cut point and 91.3% (95% CI, 87.6-94.0) for the 50% cut point. For interobserver
reproducibility, OPA was 84.2% (95% CI, 82.8-85.5) for the 1% cut point and 81.9%
(95% CI, 80.4-83.3) for the 50% cut point, and Cohen's kappa coefficients were
0.68 (95% CI, 0.65-0.71) and 0.58 (95% CI, 0.55-0.62), respectively. The training
was found to have no or very little impact on intra- or interobserver
reproducibility.Conclusions: Pathologists reported good reproducibility at both
1% and 50% cut points. More adapted training could potentially increase
reliability, in particular for samples with PD-L1 proportion, scores around 50%.
Clin Cancer Res; 23(16); 4569-77. (c)2017 AACR.
PMID- 28420728
TI - A membrane-embedded pathway delivers general anesthetics to two interacting
binding sites in the Gloeobacter violaceus ion channel.
AB - General anesthetics exert their effects on the central nervous system by acting
on ion channels, most notably pentameric ligand-gated ion channels. Although
numerous studies have focused on pentameric ligand-gated ion channels, the
details of anesthetic binding and channel modulation are still debated. A better
understanding of the anesthetic mechanism of action is necessary for the
development of safer and more efficacious drugs. Herein, we present a
computational study identifying two anesthetic binding sites in the transmembrane
domain of the Gloeobacter violaceus ligand-gated ion channel (GLIC) channel,
characterize the putative binding pathway, and observe structural changes
associated with channel function. Molecular simulations of desflurane reveal a
binding pathway to GLIC via a membrane-embedded tunnel using an intrasubunit
protein lumen as the conduit, an observation that explains the Meyer-Overton
hypothesis, or why the lipophilicity of an anesthetic and its potency are
generally proportional. Moreover, employing high concentrations of ligand led to
the identification of a second transmembrane site (TM2) that inhibits
dissociation of anesthetic from the TM1 site and is consistent with the high
concentrations of anesthetics required to achieve clinical effects. Finally,
asymmetric binding patterns of anesthetic to the channel were found to promote an
iris-like conformational change that constricts and dehydrates the ion pore,
creating a 13.5 kcal/mol barrier to ion translocation. Together with previous
studies, the simulations presented herein demonstrate a novel anesthetic binding
site in GLIC that is accessed through a membrane-embedded tunnel and interacts
with a previously known site, resulting in conformational changes that produce a
non-conductive state of the channel.
PMID- 28420729
TI - Factor V has an anticoagulant cofactor activity that targets the early phase of
coagulation.
AB - Tissue factor pathway inhibitor (TFPI), the main inhibitor of initiation of
coagulation, exerts an important anticoagulant role through the factor Xa (FXa)
dependent inhibition of tissue factor/factor VIIa. Protein S is a TFPI cofactor,
enhancing the efficiency of FXa inhibition. TFPI can also inhibit prothrombinase
assembly by directly interacting with coagulation factor V (FV), which has been
activated by FXa. Because full-length TFPI associates with FV in plasma, we
hypothesized that FV may influence TFPI inhibitory function. Using pure component
FXa inhibition assays, we found that although FV alone did not influence TFPI
mediated FXa inhibition, it further enhanced TFPI in the presence of protein S,
resulting in an ~8-fold reduction in Ki compared with TFPI alone. A FV variant
(R709Q/R1018Q/R1545Q, FVDeltaIIa) that cannot be cleaved/activated by thrombin or
FXa also enhanced TFPI-mediated inhibition of FXa ~12-fold in the presence of
protein S. In contrast, neither activated FV nor recombinant B-domain-deleted FV
could enhance TFPI-mediated inhibition of FXa in the presence of protein S,
suggesting a functional contribution of the B domain. Using TFPI and protein S
variants, we show further that the enhancement of TFPI-mediated FXa inhibition by
protein S and FV depends on a direct protein S/TFPI interaction and that the TFPI
C-terminal tail is not essential for this enhancement. In FXa-catalyzed
prothrombin activation assays, both FV and FVDeltaIIa (but not activated FV)
enhanced TFPI function in the presence of protein S. These results demonstrate a
new anticoagulant (cofactor) function of FV that targets the early phase of
coagulation before prothrombinase assembly.
PMID- 28420730
TI - Structure and characterization of a class 3B proline utilization A: Ligand
induced dimerization and importance of the C-terminal domain for catalysis.
AB - The bifunctional flavoenzyme proline utilization A (PutA) catalyzes the two-step
oxidation of proline to glutamate using separate proline dehydrogenase (PRODH)
and l-glutamate-gamma-semialdehyde dehydrogenase active sites. Because PutAs
catalyze sequential reactions, they are good systems for studying how metabolic
enzymes communicate via substrate channeling. Although mechanistically similar,
PutAs vary widely in domain architecture, oligomeric state, and quaternary
structure, and these variations represent different structural solutions to the
problem of sequestering a reactive metabolite. Here, we studied PutA from
Corynebacterium freiburgense (CfPutA), which belongs to the uncharacterized 3B
class of PutAs. A 2.7 A resolution crystal structure showed the canonical
arrangement of PRODH, l-glutamate-gamma-semialdehyde dehydrogenase, and C
terminal domains, including an extended interdomain tunnel associated with
substrate channeling. The structure unexpectedly revealed a novel open
conformation of the PRODH active site, which is interpreted to represent the non
activated conformation, an elusive form of PutA that exhibits suboptimal
channeling. Nevertheless, CfPutA exhibited normal substrate-channeling activity,
indicating that it isomerizes into the active state under assay conditions.
Sedimentation-velocity experiments provided insight into the isomerization
process, showing that CfPutA dimerizes in the presence of a proline analog and
NAD+ These results are consistent with the morpheein model of enzyme hysteresis,
in which substrate binding induces conformational changes that promote assembly
of a high-activity oligomer. Finally, we used domain deletion analysis to
investigate the function of the C-terminal domain. Although this domain contains
neither catalytic residues nor substrate sites, its removal impaired both
catalytic activities, suggesting that it may be essential for active-site
integrity.
PMID- 28420731
TI - Distinct modulatory role of RNA in the aggregation of the tumor suppressor
protein p53 core domain.
AB - Inactivation of the tumor suppressor protein p53 by mutagenesis, chemical
modification, protein-protein interaction, or aggregation has been associated
with different human cancers. Although DNA is the typical substrate of p53,
numerous studies have reported p53 interactions with RNA. Here, we have examined
the effects of RNA of varied sequence, length, and origin on the mechanism of
aggregation of the core domain of p53 (p53C) using light scattering, intrinsic
fluorescence, transmission electron microscopy, thioflavin-T binding, seeding,
and immunoblot assays. Our results are the first to demonstrate that RNA can
modulate the aggregation of p53C and full-length p53. We found bimodal behavior
of RNA in p53C aggregation. A low RNA:protein ratio (~1:50) facilitates the
accumulation of large amorphous aggregates of p53C. By contrast, at a high
RNA:protein ratio (>=1:8), the amorphous aggregation of p53C is clearly
suppressed. Instead, amyloid p53C oligomers are formed that can act as seeds
nucleating de novo aggregation of p53C. We propose that structured RNAs prevent
p53C aggregation through surface interaction and play a significant role in the
regulation of the tumor suppressor protein.
PMID- 28420732
TI - Modulation of TMEM16A channel activity by the von Willebrand factor type A (VWA)
domain of the calcium-activated chloride channel regulator 1 (CLCA1).
AB - Calcium-activated chloride channels (CaCCs) are key players in transepithelial
ion transport and fluid secretion, smooth muscle constriction, neuronal
excitability, and cell proliferation. The CaCC regulator 1 (CLCA1) modulates the
activity of the CaCC TMEM16A/Anoctamin 1 (ANO1) by directly engaging the channel
at the cell surface, but the exact mechanism is unknown. Here we demonstrate that
the von Willebrand factor type A (VWA) domain within the cleaved CLCA1 N-terminal
fragment is necessary and sufficient for this interaction. TMEM16A protein levels
on the cell surface were increased in HEK293T cells transfected with CLCA1
constructs containing the VWA domain, and TMEM16A-like currents were activated.
Similar currents were evoked in cells exposed to secreted VWA domain alone, and
these currents were significantly knocked down by TMEM16A siRNA. VWA-dependent
TMEM16A modulation was not modified by the S357N mutation, a VWA domain
polymorphism associated with more severe meconium ileus in cystic fibrosis
patients. VWA-activated currents were significantly reduced in the absence of
extracellular Mg2+, and mutation of residues within the conserved metal ion
dependent adhesion site motif impaired the ability of VWA to potentiate TMEM16A
activity, suggesting that CLCA1-TMEM16A interactions are Mg2+- and metal ion
dependent adhesion site-dependent. Increase in TMEM16A activity occurred within
minutes of exposure to CLCA1 or after a short treatment with nocodazole,
consistent with the hypothesis that CLCA1 stabilizes TMEM16A at the cell surface
by preventing its internalization. Our study hints at the therapeutic potential
of the selective activation of TMEM16A by the CLCA1 VWA domain in loss-of
function chloride channelopathies such as cystic fibrosis.
PMID- 28420734
TI - MINK1: The missing link between ROS and its inhibition of Th17 cells.
AB - In this issue of JEM, Fu et al. (https://doi.org/10.1084/jem.20161120) identified
the kinase Mink1 as a novel negative regulator of Th17 cell generation. Mink1,
activated by reactive oxygen species (ROS), prevents TGF-beta activation of
Smad2, therefore limiting Th17 cell differentiation.
PMID- 28420733
TI - Detection of interferon alpha protein reveals differential levels and cellular
sources in disease.
AB - Type I interferons (IFNs) are essential mediators of antiviral responses. These
cytokines have been implicated in the pathogenesis of autoimmunity, most notably
systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as
well as monogenic type I interferonopathies. Despite a fundamental role in health
and disease, the direct quantification of type I IFNs has been challenging. Using
single-molecule array (Simoa) digital ELISA technology, we recorded attomolar
concentrations of IFNalpha in healthy donors, viral infection, and complex and
monogenic interferonopathies. IFNalpha protein correlated well with functional
activity and IFN-stimulated gene expression. High circulating IFNalpha levels
were associated with increased clinical severity in SLE patients, and a study of
the cellular source of IFNalpha protein indicated disease-specific mechanisms.
Measurement of IFNalpha attomolar concentrations by digital ELISA will enhance
our understanding of IFN biology and potentially improve the diagnosis and
stratification of pathologies associated with IFN dysregulation.
PMID- 28420735
TI - Correction: The soluble pattern recognition receptor PTX3 links humoral innate
and adaptive immune responses by helping marginal zone B cells.
PMID- 28420736
TI - Deciphering the Regulatory Network between the SREBP Pathway and Protein
Secretion in Neurospora crassa.
AB - Sterol regulatory element binding proteins (SREBPs) are conserved from yeast to
mammalian cells and function in the regulation of sterol homeostasis. In fungi,
the SREBP pathway has been implicated in the adaptation to hypoxia and in
virulence. In Neurospora crassa and Trichoderma reesei, the SREBP pathway also
negatively regulates protein secretion under lignocellulolytic conditions. Here
we utilized global transcriptional profiling combined with genetic and
physiological analyses to address the regulatory link between the SREBP pathway
and protein secretion in N. crassa Our results demonstrated that the function of
the SREBP pathway in ergosterol biosynthesis and adaptation to hypoxia was
conserved in N. crassa Under lignocellulolytic conditions, the SREBP pathway was
highly activated, resulting in the reduced expression of lytic polysaccharide
monooxygenases, which require molecular oxygen for catalytic activity.
Additionally, activation of the SREBP pathway under lignocellulolytic conditions
repressed a set of genes predicted to be involved in the endoplasmic reticulum
stress response. Here we show that the inability of a hac-1 mutant, which bears a
deletion of the major regulator of the unfolded protein response (UPR), to
efficiently produce cellulases and utilize cellulose was suppressed by mutations
in the SREBP pathway. The analyses presented here demonstrated new SREBP pathway
functions, including linkages to the UPR, and provide new clues for genetic
engineering of filamentous fungi to improve their production of extracellular
proteins.IMPORTANCE The role of SREBP transcription factors in the regulation of
sterol biosynthesis is conserved from humans to yeast. In filamentous fungi, this
pathway regulates the secretion of lignocellulolytic enzymes during plant biomass
deconstruction. Here we show that the SREBP pathway in Neurospora crassa
regulates the production of specific cellulases, lytic polysaccharide
monooxygenases that utilize molecular oxygen. Via global transcriptional profile
and genetic analyses, a relationship between the SREBP pathway and the unfolded
protein response (UPR) pathway was revealed, suggesting a regulatory interplay of
these two pathways in the trafficking of plant biomass-degrading enzymes. These
findings have implications for our understanding of the cross talk of the SREBP
and UPR pathways in other organisms and will guide the rational engineering of
fungal strains to improve cellulolytic enzyme production.
PMID- 28420737
TI - Tolerant, Growing Cells from Nutrient Shifts Are Not Persister Cells.
AB - There is much controversy about the metabolic state of cells that are tolerant to
antibiotics, known as persister cells. In this opinion piece, we offer an
explanation for the discrepancy seen: some laboratories are studying
metabolically active and growing cell populations (e.g., as a result of nutrient
shifts) and attributing the phenotypes that they discern to persister cells while
other labs are studying dormant cells. We argue here that the metabolically
active cell population should more accurately be considered tolerant cells, while
the dormant cells are the true persister population.
PMID- 28420738
TI - SAR202 Genomes from the Dark Ocean Predict Pathways for the Oxidation of
Recalcitrant Dissolved Organic Matter.
AB - Deep-ocean regions beyond the reach of sunlight contain an estimated 615 Pg of
dissolved organic matter (DOM), much of which persists for thousands of years. It
is thought that bacteria oxidize DOM until it is too dilute or refractory to
support microbial activity. We analyzed five single-amplified genomes (SAGs) from
the abundant SAR202 clade of dark-ocean bacterioplankton and found they encode
multiple families of paralogous enzymes involved in carbon catabolism, including
several families of oxidative enzymes that we hypothesize participate in the
degradation of cyclic alkanes. The five partial genomes encoded 152 flavin
mononucleotide/F420-dependent monooxygenases (FMNOs), many of which are predicted
to be type II Baeyer-Villiger monooxygenases (BVMOs) that catalyze oxygen
insertion into semilabile alicyclic alkanes. The large number of oxidative
enzymes, as well as other families of enzymes that appear to play complementary
roles in catabolic pathways, suggests that SAR202 might catalyze final steps in
the biological oxidation of relatively recalcitrant organic compounds to
refractory compounds that persist.IMPORTANCE Carbon in the ocean is massively
sequestered in a complex mixture of biologically refractory molecules that
accumulate as the chemical end member of biological oxidation and diagenetic
change. However, few details are known about the biochemical machinery of carbon
sequestration in the deep ocean. Reconstruction of the metabolism of a deep-ocean
microbial clade, SAR202, led to postulation of new biochemical pathways that may
be the penultimate stages of DOM oxidation to refractory forms that persist.
These pathways are tied to a proliferation of oxidative enzymes. This research
illuminates dark-ocean biochemistry that is broadly consequential for
reconstructing the global carbon cycle.
PMID- 28420740
TI - Erratum for Roth et al., "Flavivirus Infection Uncouples Translation Suppression
from Cellular Stress Responses".
PMID- 28420739
TI - The DnaK Chaperone Uses Different Mechanisms To Promote and Inhibit Replication
of Vibrio cholerae Chromosome 2.
AB - Replication of Vibrio cholerae chromosome 2 (Chr2) depends on molecular chaperone
DnaK to facilitate binding of the initiator (RctB) to the replication origin. The
binding occurs at two kinds of site, 12-mers and 39-mers, which promote and
inhibit replication, respectively. Here we show that DnaK employs different
mechanisms to enhance the two kinds of binding. We found that mutations in rctB
that reduce DnaK binding also reduce 12-mer binding and initiation. The
initiation defect is suppressed by second-site mutations that increase 12-mer
binding only marginally. Instead, they reduce replication inhibitory mechanisms:
RctB dimerization and 39-mer binding. One suppressing change was in a
dimerization domain which is folded similarly to the initiator of an iteron
plasmid-the presumed progenitor of Chr2. In plasmids, DnaK promotes initiation by
reducing dimerization. A different mutation was in the 39-mer binding domain of
RctB and inactivated it, indicating an alternative suppression mechanism.
Paradoxically, although DnaK increases 39-mer binding, the increase was also
achieved by inactivating the DnaK binding site of RctB. This result suggests that
the site inhibits the 39-mer binding domain (via autoinhibition) when prevented
from binding DnaK. Taken together, our results reveal an important feature of the
transition from plasmid to chromosome: the Chr2 initiator retains the plasmid
like dimerization domain and its control by chaperones but uses the chaperones in
an unprecedented way to control the inhibitory 39-mer binding.IMPORTANCE The
capacity of proteins to undergo remodeling provides opportunities to control
their function. However, remodeling remains a poorly understood aspect of the
structure-function paradigm due to its dynamic nature. Here we have studied
remodeling of the initiator of replication of Vibrio cholerae Chr2 by the
molecular chaperone, DnaK. We show that DnaK binds to a site on the Chr2
initiator (RctB) that promotes initiation by reducing the initiator's propensity
to dimerize. Dimerization of the initiator of the putative plasmid progenitor of
Chr2 is also reduced by DnaK, which promotes initiation. Paradoxically, the DnaK
binding also promotes replication inhibition by reducing an autoinhibitory
activity of RctB. In the plasmid-to-chromosome transition, it appears that the
initiator has acquired an autoinhibitory activity and along with it a new
chaperone activity that apparently helps to control replication inhibition
independently of replication promotion.
PMID- 28420741
TI - New Mechanism by Which Human Cytomegalovirus MicroRNAs Negate the Proinflammatory
Response to Infection.
AB - Viruses have evolved many novel mechanisms to promote infection and to mitigate
the host cell response to that infection. In the article by M. H. Hancock et al.
(mBio 8:e00109-17, 2017, https://doi.org/10.1128/mBio.00109-17), the authors
describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs;
miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The
authors document that these two viral miRNAs downregulate the NF-kappaB response
through direct targeting of the IKKalpha and IKKbeta mRNAs, which in turn,
through diminished IkappaB kinases (IKKs), block production of proinflammatory
cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF
alpha]). Because most signaling pathways that promote NF-kappaB activation and
nuclear translocation ultimately converge on the activation of the IKK complex,
this new study documents that HCMV can strongly dictate how infected cells
respond to internal and/or external stimuli and thus positively influence the
outcome of both lytic and latent infection.
PMID- 28420742
TI - Synergistic Internal Ribosome Entry Site/MicroRNA-Based Approach for Flavivirus
Attenuation and Live Vaccine Development.
AB - The recent emergence of Zika virus underscores the need for new strategies for a
rapid development of safe flavivirus vaccines. Using another flavivirus (Langat
virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we
describe a dual strategy for virus attenuation which synergistically accesses the
specificity of microRNA (miRNA) genome targeting and the effectiveness of
internal ribosome entry site (IRES) insertion. To increase the stability and
immunogenicity of bicistronic LGTVs, we developed a novel approach in which the
capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and
expressed under translational control from an IRES. Engineered bicistronic LGTVs
carrying multiple target sequences for brain-specific miRNAs were stable in Vero
cells and induced adaptive immunity in mice. Importantly, miRNA-targeted
bicistronic LGTVs were not pathogenic for either newborn mice after intracranial
inoculation or adult immunocompromised mice (SCID or type I interferon receptor
knockout) after intraperitoneal injection. Moreover, bicistronic LGTVs were
restricted for replication in tick-derived cells, suggesting an interruption of
viral transmission in nature by arthropod vectors. This approach is suitable for
reliable attenuation of many flaviviruses and may enable development of live
attenuated flavivirus vaccines.IMPORTANCE The recent emergence of Zika virus
underscores the need for new strategies for a rapid development of safe
flavivirus vaccines. Allied separately attenuating approaches based on (i)
microRNA genome targeting and (ii) internal ribosome entry site insertion are not
sufficient for relievable attenuation of neurotropic flavivirus pathogenesis.
Here, we describe a novel dual strategy that combines the specificity of miRNA
based and the effectiveness of IRES-based attenuating approaches, allowing us to
overcome these critical limitations. This developed approach provides a robust
platform for reliable attenuation of many flaviviruses and may enable development
of live flavivirus vaccines.
PMID- 28420743
TI - Cancer cell metabolism: the essential role of the nonessential amino acid,
glutamine.
AB - Biochemistry textbooks and cell culture experiments seem to be telling us two
different things about the significance of external glutamine supply for
mammalian cell growth and proliferation. Despite the fact that glutamine is a
nonessential amino acid that can be synthesized by cells from glucose-derived
carbons and amino acid-derived ammonia, most mammalian cells in tissue culture
cannot proliferate or even survive in an environment that does not contain
millimolar levels of glutamine. Not only are the levels of glutamine in standard
tissue culture media at least ten-fold higher than other amino acids, but
glutamine is also the most abundant amino acid in the human bloodstream, where it
is assiduously maintained at approximately 0.5 mM through a combination of
dietary uptake, de novo synthesis, and muscle protein catabolism. The complex
metabolic logic of the proliferating cancer cells' appetite for glutamine-which
goes far beyond satisfying their protein synthesis requirements-has only recently
come into focus. In this review, we examine the diversity of biosynthetic and
regulatory uses of glutamine and their role in proliferation, stress resistance,
and cellular identity, as well as discuss the mechanisms that cells utilize in
order to adapt to glutamine limitation.
PMID- 28420744
TI - The transcription factor bZIP14 regulates the TCA cycle in the diatom
Phaeodactylum tricornutum.
AB - Diatoms are amongst the most important marine microalgae in terms of biomass, but
little is known concerning the molecular mechanisms that regulate their versatile
metabolism. Here, the pennate diatom Phaeodactylum tricornutum was studied at the
metabolite and transcriptome level during nitrogen starvation and following
imposition of three other stresses that impede growth. The coordinated
upregulation of the tricarboxylic acid (TCA) cycle during the nitrogen stress
response was the most striking observation. Through co-expression analysis and
DNA binding assays, the transcription factor bZIP14 was identified as a regulator
of the TCA cycle, also beyond the nitrogen starvation response, namely in diurnal
regulation. Accordingly, metabolic and transcriptional shifts were observed upon
overexpression of bZIP14 in transformed P. tricornutum cells. Our data indicate
that the TCA cycle is a tightly regulated and important hub for carbon
reallocation in the diatom cell during nutrient starvation and that bZIP14 is a
conserved regulator of this cycle.
PMID- 28420745
TI - Eight principles for patient-centred and family-centred care for newborns in the
neonatal intensive care unit.
AB - Despite the recent improvements in perinatal medical care leading to an increase
in survival rates, adverse neurodevelopmental outcomes occur more frequently in
preterm and/or high-risk infants. Medical risk factors for neurodevelopmental
delays like male gender or intrauterine growth restriction and family
sociocultural characteristics have been identified. Significant data have
provided evidence of the detrimental impact of overhelming environmental sensory
inputs, such as pain and stress, on the developing human brain and strategies
aimed at preventing this impact. These strategies, such as free parental access
or sleep protection, could be considered 'principles of care'. Implementation of
these principles do not require additional research due to the body of evidence.
We review the scientific evidence for these principles here.
PMID- 28420747
TI - CORRECTION.
PMID- 28420749
TI - Inner Workings: 3D printer innovations tackle complexity of metamaterials, living
tissue.
PMID- 28420746
TI - The Mitochondrial DNA-Associated Protein SWIB5 Influences mtDNA Architecture and
Homologous Recombination.
AB - In addition to the nucleus, mitochondria and chloroplasts in plant cells also
contain genomes. Efficient DNA repair pathways are crucial in these organelles to
fix damage resulting from endogenous and exogenous factors. Plant organellar
genomes are complex compared with their animal counterparts, and although several
plant-specific mediators of organelle DNA repair have been reported, many
regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF
(nucleosome remodeling) complex B protein, SWIB5, is capable of associating with
mitochondrial DNA (mtDNA) in Arabidopsis thaliana Gain- and loss-of-function
mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture
and homologous recombination at specific intermediate-sized repeats both under
normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB
proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family
members suggests a link between organellar genome maintenance and cell
proliferation. Taken together, our work presents a protein family that influences
mtDNA architecture and homologous recombination in plants and suggests a link
between organelle functioning and plant development.
PMID- 28420751
TI - Control of potassium homeostasis is an essential function of the second messenger
cyclic di-AMP in Bacillus subtilis.
AB - The second messenger cyclic di-adenosine monophosphate (c-di-AMP) is essential in
the Gram-positive model organism Bacillus subtilis and in related pathogenic
bacteria. It controls the activity of the conserved ydaO riboswitch and of
several proteins involved in potassium (K+) uptake. We found that the YdaO
protein was conserved among several different bacteria and provide evidence that
YdaO functions as a K+ transporter. Thus, we renamed the gene and protein KimA
(K+ importer A). Reporter activity assays indicated that expression beyond the c
di-AMP-responsive riboswitch of the kimA upstream regulatory region occurred only
in bacteria grown in medium containing low K+ concentrations. Furthermore, mass
spectrometry analysis indicated that c-di-AMP accumulated in bacteria grown in
the presence of high K+ concentrations but not in low concentrations. A bacterial
strain lacking all genes encoding c-di-AMP-synthesizing enzymes was viable when
grown in medium containing low K+ concentrations, but not at higher K+
concentrations unless it acquired suppressor mutations in the gene encoding the
cation exporter NhaK. Thus, our results indicated that the control of potassium
homeostasis is an essential function of c-di-AMP.
PMID- 28420752
TI - Highlight: A new way to block the development of asthma from dust mites.
AB - Targeting a transcription factor, generally considered to be "nondruggable," may
help to prevent asthma from developing.
PMID- 28420756
TI - Microbes stimulate hair follicles.
AB - Commensal microbes induce hair follicles to release a chemokine that recruits
regulatory T cells into neonatal skin.
PMID- 28420753
TI - The kinase TPL2 activates ERK and p38 signaling to promote neutrophilic
inflammation.
AB - Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated
protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases
MEK1 and MEK2 (MEK1/2), which, in turn, activate the MAPKs extracellular signal
regulated kinase 1 (ERK1) and ERK2 (ERK1/2) in macrophages stimulated through the
interleukin-1 receptor (IL-1R), Toll-like receptors (TLRs), or the tumor necrosis
factor receptor (TNFR). We describe a conserved and critical role for TPL2 in
mediating the effector functions of neutrophils through the activation of the p38
MAPK signaling pathway. Gene expression profiling and functional studies of
neutrophils and monocytes revealed a MEK1/2-independent branch point downstream
of TPL2 in neutrophils. Biochemical analyses identified the MAPK kinases MEK3 and
MEK6 and the MAPKs p38alpha and p38delta as downstream effectors of TPL2 in these
cells. Genetic ablation of the catalytic activity of TPL2 or therapeutic
intervention with a TPL2-specific inhibitor reduced the production of
inflammatory mediators by neutrophils in response to stimulation with the TLR4
agonist lipopolysaccharide (LPS) in vitro, as well as in rodent models of
inflammatory disease. Together, these data suggest that TPL2 is a drug target
that activates not only MEK1/2-dependent but also MEK3/6-dependent signaling to
promote inflammatory responses.
PMID- 28420757
TI - Stress signals in plants.
AB - Selective autophagy mediates the cross-talk between plant growth and stress
signaling pathways.
PMID- 28420758
TI - The FOXM1 inhibitor RCM-1 suppresses goblet cell metaplasia and prevents IL-13
and STAT6 signaling in allergen-exposed mice.
AB - Goblet cell metaplasia and excessive mucus secretion associated with asthma,
cystic fibrosis, and chronic obstructive pulmonary disease contribute to
morbidity and mortality worldwide. We performed a high-throughput screen to
identify small molecules targeting a transcriptional network critical for the
differentiation of goblet cells in response to allergens. We identified RCM-1, a
nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus
production in mice after exposure to allergens. RCM-1 blocked the nuclear
localization and increased the proteasomal degradation of Forkhead box M1
(FOXM1), a transcription factor critical for the differentiation of goblet cells
from airway progenitor cells. RCM-1 reduced airway resistance, increased lung
compliance, and decreased proinflammatory cytokine production in mice exposed to
the house dust mite and interleukin-13 (IL-13), which triggers goblet cell
metaplasia. In cultured airway epithelial cells and in mice, RCM-1 reduced IL-13
and STAT6 (signal transducer and activator of transcription 6) signaling and
prevented the expression of the STAT6 target genes Spdef and Foxa3, which are key
transcriptional regulators of goblet cell differentiation. These results suggest
that RCM-1 is an inhibitor of goblet cell metaplasia and IL-13 signaling,
providing a new therapeutic candidate to treat patients with asthma and other
chronic airway diseases.
PMID- 28420760
TI - Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal
tubular epithelial cells under hypoxia.
AB - Chronic tubulointerstitial hypoxia plays an important role as the final common
pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a
master transcriptional factor under hypoxia, regulating downstream target genes.
Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has
clarified various kinds of downstream targets and made it possible to demonstrate
the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1
downstream epigenetic targets which may play important roles in the kidney.
Immortalized tubular cell lines (HK2; human kidney-2) and primary cultured cells
(RPTEC; renal proximal tubular cell lines) were exposed to 1% hypoxia for 24-72
h. We performed RNA-seq to clarify the expression of mRNA and long non-coding RNA
(lncRNA). We also examined ChIP-seq to identify HIF-1 binding sites under
hypoxia. RNA-seq identified 44 lncRNAs which are up-regulated under hypoxic
condition in both cells. ChIP-seq analysis demonstrated that HIF-1 also binds to
the lncRNAs under hypoxia. The expression of novel lncRNA, DARS-AS1 (aspartyl
tRNA synthetase anti-sense 1), is up-regulated only under hypoxia and HIF-1 binds
to its promoter region, which includes two hypoxia-responsive elements. Its
expression is also up-regulated with cobalt chloride exposure, while it is not
under hypoxia when HIF-1 is knocked down by siRNA To clarify the biological roles
of DARS-AS1, we measured the activity of caspase 3/7 using anti-sense oligo of
DARS-AS1. Knockdown of DARS-AS1 deteriorated apoptotic cell death. In conclusion,
we identified the novel lncRNAs regulated by HIF-1 under hypoxia and clarified
that DARS-AS1 plays an important role in inhibiting apoptotic cell death in renal
tubular cells.
PMID- 28420761
TI - In-situ measurements of tensile forces in the tibialis anterior tendon of the rat
in concentric, isometric, and resisted co-contractions.
AB - Tensile-force transmitted by the tibialis anterior (TA) tendon of 11 anesthetized
adult male Wistar rats (body-mass: 360.6 +/- 66.3 g) was measured in-situ within
the intact biomechanical system of the hind-limb using a novel miniature in-line
load-cell. The aim was to demonstrate the dependence of the loading-profile
experienced by the muscle, on stimulation-frequency and the resistance to
shortening in a group of control-animals. Data from these acute-experiments shows
the type of loading achievable by means of implantable electrical stimulators
activating agonists or agonist/antagonist groups of muscles during programmed
resistance-training in freely moving healthy subjects. Force-responses to
electrical stimulation of the common peroneal nerve for single pulses and short
bursts were measured in unloaded and isometric contractions. A less time
consuming approach to measure the force-frequency relationship was investigated
by applying single bursts containing a series of escalating stimulus-frequencies.
We also measured the range of loading attainable by programmed co-contraction of
the TA-muscle with the plantar-flexor muscles for various combinations of
stimulation-frequencies. The maximal average peak-force of single twitches was
179% higher for isometric than for unloaded twitches. Average maximal isometric
tetanic-force per gramme muscle-mass was 16.5 +/- 3.0 N g-1, which agrees well
with other studies. The standard and time-saving approaches to measure the force
frequency relationship gave similar results. Plantar-flexor co-activation
produced greatly increased tension in the TA-tendon, similar to isometric
contractions. Our results suggest that unloaded contractions may not be adequate
for studies of resistance-training. Plantar-flexor co-contractions produced
considerably higher force-levels that may be better suited to investigate the
physiology and cell-biology of resistance-training in rodents.
PMID- 28420762
TI - Resting heart rate variability and exercise capacity in Type 1 diabetes.
AB - People with type 1 diabetes (T1D) have lower exercise capacity (VO2max) than
their age-matched nondiabetic counterparts (CON), which might be related to
cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV;
indicator of cardiac autonomic modulation) was associated with exercise capacity
in those with and without T1D. Twenty-three participants with uncomplicated T1D
and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP;
finger photo-plethysmography), and respiratory rate (respiratory belt) were
measured during baseline, paced-breathing and clinical autonomic reflex tests
(CARTs); deep breathing, lying-to-stand, and Valsalva maneuver. Baseline and
paced-breathing ECG were analyzed for HRV (frequency-domain). Exercise capacity
was determined during an incremental cycle ergometer test while VO2, 12-lead ECG,
and BP were measured. In uncomplicated T1D, resting HR was elevated and resting
HRV metrics were reduced, indicative of altered cardiac parasympathetic
modulation; this was generally undetected by the CARTs. However, BP and plasma
catecholamines were not different between groups. In T1D, VO2max tended to be
lower (P = 0.07) and HR reserve was lower (P < 0.01). Resting Total Power (TP)
had stronger positive associations with VO2max (R2 >= 0.3) than all other
traditional indicators such as age, resting HR, and self-reported exercise (R2 =
0.042-0.3) in both T1D and CON Alterations in cardiac autonomic modulation are an
early manifestation of uncomplicated T1D. Total Power was associated with reduced
exercise capacity regardless of group, and these associations were generally
stronger than traditional indicators.
PMID- 28420764
TI - Erratum.
PMID- 28420763
TI - Reduced body weight gain in ubiquilin-1 transgenic mice is associated with
increased expression of energy-sensing proteins.
AB - Ubiquilin-1 (Ubqln1), a ubiquitin-like protein, is implicated in a variety of
pathophysiological processes, but its role in mediating body weight gain or
metabolism has not been determined. Here, we demonstrate that global
overexpression of Ubqln1 in a transgenic (Tg) mouse reduces the animal's body
weight gain. The decreased body weight gain in Tg mice is associated with lower
visceral fat content and higher metabolic rate. The Ubqln1 Tg mice exhibited
reduced leptin and insulin levels as well as increased insulin sensitivity
manifested by homeostatic model assessment of insulin resistance. Additionally,
the reduced body weight in Tg mice was associated with the upregulation of two
energy-sensing proteins, sirtuin1 (SIRT1) in the hypothalamus and AMP-activated
protein kinase (AMPK) in the skeletal muscle. Consistent with the in vivo
results, overexpression of Ubqln1 significantly increased SIRT1 and AMPK levels
in the mouse embryonic fibroblast cell culture. Thus, our results not only
establish the link between Ubqln1 and body weight regulation but also indicate
that the metabolic function of Ubqln1 on body weight may be through regulating
energy-sensing proteins.
PMID- 28420765
TI - Plan Selection in the Non-Group Market in the First Year of the Health Insurance
Marketplace.
AB - BACKGROUND The Affordable Care Act (ACA)-created Marketplaces reduced barriers to
entry in the non-group health insurance market. Although tax credits were
available to individuals who enrolled in qualified health plans (QHPs) beginning
in 2014, many individuals chose not to switch plans. We examined characteristics
associated with switching from a non-ACA compliant plan to a QHP in 2014 and,
conditional on switching, the characteristics associated with selection of a
specific plan level.METHODS Using claims data from a large commercial insurer, we
examined characteristics associated with switching to a QHP in 2014. For those
who did switch, we used a multinomial logit model to estimate odds of selecting
different metal levels-representing varying degrees of coverage-for a group of
the highest and lowest risk individuals.RESULTS We found individuals most likely
to benefit from the premium and benefit requirements on QHPs were more likely to
switch to QHPs. Individuals at high-risk for high health care expenditures who
had advance premium tax credits (APTCs) had lower odds of choosing a less
generous plan compared to individuals without APTCs (odds of bronze plan over
silver: 0.40, CI: 0.30 - 0.55), while individuals at low-risk of being high cost
with APTCs were more likely to select a plan with a lower premium (odds bronze
plan over silver: 1.35, CI: 1.09 - 1.66).LIMITATIONS This study was conducted
with data from 1 health plan, limiting its national generalizability; however,
this study is a good representation of activity within the state.CONCLUSIONS
APTCs are important for ensuring that less healthy individuals are able to afford
adequate levels of coverage.
PMID- 28420766
TI - Project ACCRUE: Exploring Options to Increase Awareness of AIDS Malignancy
Consortium Clinical Trials in North Carolina.
AB - BACKGROUND Longer lifespans conferred by antiretroviral therapy result in more
time exposed to cancer risk for people living with HIV/AIDS (PLWHA). Given
limited diversity in AIDS Malignancy Consortium (AMC) clinical trials, there is
need for new approaches to educate PLWHA in order to improve awareness and
participation in AMC trials.METHODS With input from a community advisory board,
Project ACCRUE (AMC Clinical Trials at Carolina Ramp Up Enrollment) conducted a
key informant interview with service providers; online organizational surveys of
AMC trial awareness and resource needs; and "lunch and learn" educational
sessions, including pre- and post-intervention knowledge assessments.RESULTS
Providers indicated that transportation, mistrust of the medical community, and
affordability were barriers to trial participation, while printed educational
materials could facilitate trial recruitment. Providers indicated that their
clients had concerns about participating in trials, but also recognized several
benefits of participation including access to medical personnel and treatment,
receipt of monetary incentives, and a feeling of satisfaction from helping
others. In lunch and learn sessions, use of an audience response system to
collect questionnaire data improved scores on knowledge-based items [S(55) = 460;
P < .0001] compared to a pencil and paper test [S(20) = 12.5; P =
.6541].LIMITATIONS Generalizability may have been compromised by the small sample
size. Long-term recall was not measured, and the short retest interval may have
impacted post-intervention assessments.CONCLUSIONS Service providers recognize
the benefits of working with researchers to educate patients about HIV-related
cancers and participation in clinical trials. Lunch and learn sessions improved
knowledge and perceptions about clinical trials for PLWHA.
PMID- 28420767
TI - Vision and Hearing.
PMID- 28420768
TI - Introduction to The NCMJ's Special Issue on Vision and Hearing Loss.
AB - This article introduces NCMJ's special issue on vision and hearing loss. The 13
articles are organized around four areas: 1) screening and early intervention; 2)
technology; 3) prevention; and 4) accommodation, accessibility, and
communication. Together the authors discuss a wide range of potential challenges.
However, importantly, the authors also provide a wealth of resources for
individuals, families, and health care providers.
PMID- 28420769
TI - Newborn Hearing Screening: Making a Difference.
AB - Newborn hearing screening has become the standard of care in the United States,
with over 98% of infants born screened for hearing loss. Appropriate and timely
follow-up is critical when an infant does not pass the screening. While there
remains room for improvement, newborn hearing screening is making a difference.
PMID- 28420770
TI - Accommodating Deaf and Hard-of-Hearing Employees.
AB - Hearing loss is the 2nd most prevalent health issue around the world; in the US,
about 1 in 5 people, and 3 in 5 combat veterans, have some amount of hearing loss
[1]. Managers or supervisors will inevitably have an employee who has some degree
of hearing loss. Employers have a legal obligation to make reasonable
accommodations that enable employees with disabilities, including hearing loss,
to be successful in the workplace.
PMID- 28420771
TI - Updates in Hearing Technology.
AB - Advances in hearing technology offer patients with hearing loss even better ways
to improve communication and quality of life. Hearing devices are more convenient
and compatible than ever, with wireless connectivity to smartphones and lithium
ion rechargeable batteries, while improved surgical techniques widen the
candidacy for cochlear implants to those with more residual hearing.
PMID- 28420772
TI - Health Care for Individuals with Hearing Loss or Vision Loss: A Minefield of
Barriers to Accessibility.
AB - Individuals with hearing or vision loss face significant barriers in accessing
health care, resulting in documented health inequities. These barriers are
typically in the form of inaccessible communication or information, as well as
impediments to orientation or mobility. Compliance with applicable accessibility
laws, such as the Americans with Disabilities Act, requires that providers have a
sound understanding of the specific aids and services that assure compliance.
PMID- 28420773
TI - Are Direct-to-Consumer Marketing and Over-the-Counter Sale of Hearing Aids
Beneficial to Patients with Hearing Loss? A Provider's Perspective.
PMID- 28420774
TI - Preventing Noise-Induced Hearing Loss.
AB - Noise-induced hearing loss (NIHL) is second only to presbycusis, age-related
hearing loss, as a cause of hearing impairment; yet, it is preventable. This
commentary summarizes the effects of noise on hearing, relevant workplace
regulations, and ways to minimize excessive noise's deleterious impact on
individuals' quality of life on and off the job.
PMID- 28420775
TI - The Prevalence and Impact of Vision and Hearing Loss in the Elderly.
AB - With a rapidly aging population, awareness of sensory impairments in the older
adult population is crucial. Vision and hearing loss, in particular, have a
prominent impact on quality of life. Understanding the prevalence and impact of
these impairments is important to help patients preserve and maintain a good
quality of life.
PMID- 28420776
TI - Screening for Diabetic Retinopathy: Strategies for Improving Patient Follow-up.
AB - Diabetic retinopathy is a leading cause of preventable blindness. Timely
screening and treatment prevent morbidity, though low follow-up rates remain
problematic. Feasible and efficacious methods for increasing screening follow-up
rates include patient education, a streamlined referral and scheduling process,
and collaboration with local ophthalmologists and primary care providers.
PMID- 28420777
TI - Retinopathy of Prematurity.
AB - Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder unique
to premature infants. As premature births increase in many areas of the world,
ROP has become a leading cause of childhood blindness. A better understanding of
the pathogenesis of ROP, adherence to strict screening guidelines, and evolution
of treatment options have reduced the number of sight-threatening complications
from ROP.
PMID- 28420778
TI - Empowering Adolescents Who Are Deaf and Hard of Hearing.
AB - The adolescent years are challenging for all kids. If hearing loss is added into
the mix, the issues faced by these teens are quite complex and require some skill
development in advocacy, empowerment, and independence. This article will explore
the emotional journey of the individual and the family.
PMID- 28420779
TI - Patient-Provider Communication in the Context of Hearing Loss.
AB - Hearing is the primary mechanism through which most of us receive ideas from
other people. When that ability is altered, it affects how we interpret and react
to information. In a physician's office, the transfer of thought is critical to
ensuring that patients understand their healthcare information and are compliant
with things like medication. In this article, we discuss ways to enhance that
communication.
PMID- 28420780
TI - Running the Numbers: Understanding the Prevalence of Eye and Ear Injuries in
North Carolina.
PMID- 28420781
TI - Philanthropy Profile: Promoting the Importance of Screenings for Healthier Sight
and Sound.
PMID- 28420782
TI - Downward Trends in Medicaid Costs: Let's Recognize What's Been Working!
PMID- 28420783
TI - Block Grants Would Strip Medicaid Coverage for Low Income North Carolinians.
PMID- 28420784
TI - Death Rates from Unintentional and Undetermined Prescription Opioid Overdoses and
Dispensing Rates of Controlled Prescription Opioid Analgesics - 2011-2015.
PMID- 28420785
TI - Bringing disorder and dynamics in protein allostery into focus.
PMID- 28420786
TI - Memory-n strategies of direct reciprocity.
AB - Humans routinely use conditionally cooperative strategies when interacting in
repeated social dilemmas. They are more likely to cooperate if others cooperated
before, and are ready to retaliate if others defected. To capture the emergence
of reciprocity, most previous models consider subjects who can only choose from a
restricted set of representative strategies, or who react to the outcome of the
very last round only. As players memorize more rounds, the dimension of the
strategy space increases exponentially. This increasing computational complexity
renders simulations for individuals with higher cognitive abilities infeasible,
especially if multiplayer interactions are taken into account. Here, we take an
axiomatic approach instead. We propose several properties that a robust
cooperative strategy for a repeated multiplayer dilemma should have. These
properties naturally lead to a unique class of cooperative strategies, which
contains the classical Win-Stay Lose-Shift rule as a special case. A
comprehensive numerical analysis for the prisoner's dilemma and for the public
goods game suggests that strategies of this class readily evolve across various
memory-n spaces. Our results reveal that successful strategies depend not only on
how cooperative others were in the past but also on the respective context of
cooperation.
PMID- 28420787
TI - Activation of NLRP3 inflammasome complex potentiates venous thrombosis in
response to hypoxia.
AB - Venous thromboembolism (VTE), caused by altered hemostasis, remains the third
most common cause of mortality among all cardiovascular conditions. In addition
to established genetic and acquired risk factors, low-oxygen environments also
predispose otherwise healthy individuals to VTE. Although disease etiology
appears to entail perturbation of hemostasis pathways, the key molecular
determinants during immediate early response remain elusive. Using an established
model of venous thrombosis, we here show that systemic hypoxia accelerates
thromboembolic events, functionally stimulated by the activation of nucleotide
binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3)
inflammasome complex and increased IL-1beta secretion. Interestingly, we also
show that the expression of NLRP3 is mediated by hypoxia-inducible factor 1-alpha
(HIF-1alpha) during these conditions. The pharmacological inhibition of caspase
1, in vivo knockdown of NLRP3, or HIF-1alpha other than IL-1beta-neutralizing
antibodies attenuated inflammasome activation and curtailed thrombosis under
hypoxic conditions. We extend the significance of these preclinical findings by
studying modulation of this pathway in patients with altitude-induced venous
thrombosis. Our results demonstrate distinctive, increased expression of NLRP3,
caspase-1, and IL-1beta in individuals with clinically established venous
thrombosis. We therefore propose that an early proinflammatory state in the
venous milieu, orchestrated by the HIF-induced NLRP3 inflammasome complex, is a
key determinant of acute thrombotic events during hypoxic conditions.
PMID- 28420788
TI - Reconstructing the spectrotemporal modulations of real-life sounds from fMRI
response patterns.
AB - Ethological views of brain functioning suggest that sound representations and
computations in the auditory neural system are optimized finely to process and
discriminate behaviorally relevant acoustic features and sounds (e.g.,
spectrotemporal modulations in the songs of zebra finches). Here, we show that
modeling of neural sound representations in terms of frequency-specific
spectrotemporal modulations enables accurate and specific reconstruction of real
life sounds from high-resolution functional magnetic resonance imaging (fMRI)
response patterns in the human auditory cortex. Region-based analyses indicated
that response patterns in separate portions of the auditory cortex are
informative of distinctive sets of spectrotemporal modulations. Most relevantly,
results revealed that in early auditory regions, and progressively more in
surrounding regions, temporal modulations in a range relevant for speech analysis
(~2-4 Hz) were reconstructed more faithfully than other temporal modulations. In
early auditory regions, this effect was frequency-dependent and only present for
lower frequencies (<~2 kHz), whereas for higher frequencies, reconstruction
accuracy was higher for faster temporal modulations. Further analyses suggested
that auditory cortical processing optimized for the fine-grained discrimination
of speech and vocal sounds underlies this enhanced reconstruction accuracy. In
sum, the present study introduces an approach to embed models of neural sound
representations in the analysis of fMRI response patterns. Furthermore, it
reveals that, in the human brain, even general purpose and fundamental neural
processing mechanisms are shaped by the physical features of real-world stimuli
that are most relevant for behavior (i.e., speech, voice).
PMID- 28420789
TI - Structural and stereoelectronic insights into oxygenase-catalyzed formation of
ethylene from 2-oxoglutarate.
AB - Ethylene is important in industry and biological signaling. In plants, ethylene
is produced by oxidation of 1-aminocyclopropane-1-carboxylic acid, as catalyzed
by 1-aminocyclopropane-1-carboxylic acid oxidase. Bacteria catalyze ethylene
production, but via the four-electron oxidation of 2-oxoglutarate to give
ethylene in an arginine-dependent reaction. Crystallographic and biochemical
studies on the Pseudomonas syringae ethylene-forming enzyme reveal a branched
mechanism. In one branch, an apparently typical 2-oxoglutarate oxygenase reaction
to give succinate, carbon dioxide, and sometimes pyrroline-5-carboxylate occurs.
Alternatively, Grob-type oxidative fragmentation of a 2-oxoglutarate-derived
intermediate occurs to give ethylene and carbon dioxide. Crystallographic and
quantum chemical studies reveal that fragmentation to give ethylene is promoted
by binding of l-arginine in a nonoxidized conformation and of 2-oxoglutarate in
an unprecedented high-energy conformation that favors ethylene, relative to
succinate formation.
PMID- 28420790
TI - Honeybee gut microbiota promotes host weight gain via bacterial metabolism and
hormonal signaling.
AB - Social bees harbor a simple and specialized microbiota that is spatially
organized into different gut compartments. Recent results on the potential
involvement of bee gut communities in pathogen protection and nutritional
function have drawn attention to the impact of the microbiota on bee health.
However, the contributions of gut microbiota to host physiology have yet to be
investigated. Here we show that the gut microbiota promotes weight gain of both
whole body and the gut in individual honey bees. This effect is likely mediated
by changes in host vitellogenin, insulin signaling, and gustatory response. We
found that microbial metabolism markedly reduces gut pH and redox potential
through the production of short-chain fatty acids and that the bacteria adjacent
to the gut wall form an oxygen gradient within the intestine. The short-chain
fatty acid profile contributed by dominant gut species was confirmed in vitro.
Furthermore, metabolomic analyses revealed that the gut community has striking
impacts on the metabolic profiles of the gut compartments and the hemolymph,
suggesting that gut bacteria degrade plant polymers from pollen and that the
resulting metabolites contribute to host nutrition. Our results demonstrate how
microbial metabolism affects bee growth, hormonal signaling, behavior, and gut
physicochemical conditions. These findings indicate that the bee gut microbiota
has basic roles similar to those found in some other animals and thus provides a
model in studies of host-microbe interactions.
PMID- 28420792
TI - Morality constrains the default representation of what is possible.
AB - The capacity for representing and reasoning over sets of possibilities, or modal
cognition, supports diverse kinds of high-level judgments: causal reasoning,
moral judgment, language comprehension, and more. Prior research on modal
cognition asks how humans explicitly and deliberatively reason about what is
possible but has not investigated whether or how people have a default, implicit
representation of which events are possible. We present three studies that
characterize the role of implicit representations of possibility in cognition.
Collectively, these studies differentiate explicit reasoning about possibilities
from default implicit representations, demonstrate that human adults often
default to treating immoral and irrational events as impossible, and provide a
case study of high-level cognitive judgments relying on default implicit
representations of possibility rather than explicit deliberation.
PMID- 28420791
TI - Adult enteric nervous system in health is maintained by a dynamic balance between
neuronal apoptosis and neurogenesis.
AB - According to current dogma, there is little or no ongoing neurogenesis in the
fully developed adult enteric nervous system. This lack of neurogenesis leaves
unanswered the question of how enteric neuronal populations are maintained in
adult guts, given previous reports of ongoing neuronal death. Here, we confirm
that despite ongoing neuronal cell loss because of apoptosis in the myenteric
ganglia of the adult small intestine, total myenteric neuronal numbers remain
constant. This observed neuronal homeostasis is maintained by new neurons formed
in vivo from dividing precursor cells that are located within myenteric ganglia
and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation
of the phosphatase and tensin homolog gene in this pool of adult precursors leads
to an increase in enteric neuronal number, resulting in ganglioneuromatosis,
modeling the corresponding disorder in humans. Taken together, our results show
significant turnover and neurogenesis of adult enteric neurons and provide a
paradigm for understanding the enteric nervous system in health and disease.
PMID- 28420793
TI - Regulating plant physiology with organic electronics.
AB - The organic electronic ion pump (OEIP) provides flow-free and accurate delivery
of small signaling compounds at high spatiotemporal resolution. To date, the
application of OEIPs has been limited to delivery of nonaromatic molecules to
mammalian systems, particularly for neuroscience applications. However, many long
standing questions in plant biology remain unanswered due to a lack of technology
that precisely delivers plant hormones, based on cyclic alkanes or aromatic
structures, to regulate plant physiology. Here, we report the employment of OEIPs
for the delivery of the plant hormone auxin to induce differential concentration
gradients and modulate plant physiology. We fabricated OEIP devices based on a
synthesized dendritic polyelectrolyte that enables electrophoretic transport of
aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana
seedlings in vivo was monitored in real time via dynamic fluorescent auxin
response reporters and induced physiological responses in roots. Our results
provide a starting point for technologies enabling direct, rapid, and dynamic
electronic interaction with the biochemical regulation systems of plants.
PMID- 28420794
TI - Structural features and lipid binding domain of tubulin on biomimetic
mitochondrial membranes.
AB - Dimeric tubulin, an abundant water-soluble cytosolic protein known primarily for
its role in the cytoskeleton, is routinely found to be associated with
mitochondrial outer membranes, although the structure and physiological role of
mitochondria-bound tubulin are still unknown. There is also no consensus on
whether tubulin is a peripheral membrane protein or is integrated into the outer
mitochondrial membrane. Here the results of five independent techniques-surface
plasmon resonance, electrochemical impedance spectroscopy, bilayer overtone
analysis, neutron reflectometry, and molecular dynamics simulations-suggest that
alpha-tubulin's amphipathic helix H10 is responsible for peripheral binding of
dimeric tubulin to biomimetic "mitochondrial" membranes in a manner that
differentiates between the two primary lipid headgroups found in mitochondrial
membranes, phosphatidylethanolamine and phosphatidylcholine. The identification
of the tubulin dimer orientation and membrane-binding domain represents an
essential step toward our understanding of the complex mechanisms by which
tubulin interacts with integral proteins of the mitochondrial outer membrane and
is important for the structure-inspired design of tubulin-targeting agents.
PMID- 28420795
TI - Reply to Brown and Behrmann, Cox, et al., and Kessler et al.: Data and code
sharing is the way forward for fMRI.
PMID- 28420796
TI - Reevaluating "cluster failure" in fMRI using nonparametric control of the false
discovery rate.
PMID- 28420797
TI - Controversy in statistical analysis of functional magnetic resonance imaging
data.
PMID- 28420798
TI - fMRI clustering and false-positive rates.
PMID- 28420799
TI - Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS-/-
mice.
AB - Sertoli cell (SC) proliferation in mice occurs until two weeks after birth and is
mainly regulated by FSH and thyroid hormones. Previous studies have shown that
transient neonatal hypothyroidism in laboratory rodents is able to extend SC
mitotic activity, leading ultimately to higher testis size and daily sperm
production (DSP) in adult animals. Moreover, we have shown that due to higher SC
proliferation and lower germ cell apoptosis, iNOS deficiency in mice also results
in higher testis size and DSP. Although the cell size was smaller, the Leydig
cells (LCs) number per testis also significantly increased in iNOS-/- mice. Our
aims in the present study were to investigate if the combination of neonatal
hypothyroidism and iNOS deficiency promotes additive effects in SC number, testis
size and DSP. Hypothyroidism was induced in wild-type (WT) and iNOS-/- mice using
6-propyl-2-thiouracil (PTU) through the mother's drinking water from 0 to 20 days
of age, and were sacrificed at adulthood. Our results showed that, in contrast to
the WT mice in which testis size, DSP and SC numbers increased significantly by
20, 40 and 70% respectively, after PTU treatment, no additive effects were
observed for these parameters in treated iNOS-/- mice, as well as for LC. No
alterations were observed in spermatogenesis in any group evaluated. Although we
still do not have an explanation for these intriguing findings, we are currently
investigating whether thyroid hormones influence iNOS levels and/or
counterbalance physiological effects of iNOS deficiency in testis function and
spermatogenesis.
PMID- 28420800
TI - SETDB1 plays an essential role in maintenance of gonocyte survival in pigs.
AB - Histone methyltransferase SETDB1 suppresses gene expression and modulates
heterochromatin formation through H3K9me2/3. Previous studies have revealed that
SETDB1 catalyzes lysine 9 of histone H3 tri-methylation and plays essential roles
in maintaining the survival of embryonic stem cells and spermatogonial stem cells
in mice. However, the function of SETDB1 in porcine male germ cells remains
unclear. The aim of the present study was to reveal the expression profile and
function of SETDB1 in porcine germ cells. SETDB1 expression gradually increased
during testis development. SETDB1 was strongly localized in gonocytes. Knockdown
of SETDB1 gene expression led to gonocyte apoptosis and a decrease in H3K27me3,
but no significant change in H3K9me3. These observations suggested that SETDB1 is
a novel epigenetic regulator of porcine male germ cells, and contributes to the
maintenance of gonocyte survival in pigs, probably due to the regulation of
H3K27me3 rather than H3K9me3. These findings will provide a theoretical basis for
the future study of epigenetic regulation of spermatogenesis.
PMID- 28420801
TI - The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta
analysis.
AB - Laparoscopic ovarian drilling (LOD) has been widely used as an effective
treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However,
there has been a growing concern over a possible damaging effect of this
procedure on ovarian reserve. The objective of this study was to investigate the
hypothesis that LOD compromises ovarian reserve as measured by post-operative
changes in circulating anti-Mullerian hormone (AMH). This meta-analysis included
all cohort studies as well as randomised controlled trials (RCTs) investigating
serum AMH concentrations and other ovarian reserve markers in women with PCOS
undergoing LOD. Various databases were searched including MEDLINE, EMBASE,
Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane
Library from January 2000 to December 2016. Sixty studies were identified, of
which seven were deemed eligible for this review. AMH data were extracted from
each study and entered into the RevMan software to calculate the weighted mean
difference (WMD) between pre- and post-operative values. Pooled analysis of all
studies (n = 442) revealed a statistically significant decline in serum AMH
concentration after LOD (WMD -2.13 ng/mL; 95% confidence interval (CI) -2.97 to
1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of
surgery and amount of energy applied during LOD consistently showed a
statistically significant fall in serum AMH concentration. In conclusion,
although LOD seems to markedly reduce circulating AMH, it remains uncertain
whether this reflects a real damage to ovarian reserve or normalisation of the
high pre-operative serum AMH levels. Further long-term studies on ovarian reserve
after LOD are required to address this uncertainty.
PMID- 28420802
TI - Clinical Decision-Making for the Hemodynamic "Gray Zone" (FFR 0.75-0.80) and Long
Term Outcomes.
AB - BACKGROUND: Fractional flow reserve (FFR) value between 0.75 and 0.80 is
considered the "gray zone" and outcomes data relative to treatment strategy
(revascularization vs medical therapy alone [deferral]) are limited for this
group. METHODS AND RESULTS: A total of 238 patients (64.3 +/- 8.6 years; 97%
male; 45% diabetic) with gray-zone FFR were followed for the primary endpoint of
major adverse cardiovascular event (MACE), defined as a composite of death,
myocardial infarction (MI), and target-vessel revascularization. Mean follow-up
duration was 30 +/- 17 months. Deferred patients (n = 48 [20%]) had a higher
prevalence of smoking and chronic kidney disease compared with the percutaneous
coronary intervention (PCI) group (n = 190 [80%]; P<.05). Patients who underwent
PCI had significantly lower MACE compared with the deferred patients (16% vs 40%;
log rank P<.01). While there was a trend toward a decrease in all-cause mortality
(8% vs 19%; log rank P=.06), the composite of death or MI was significantly lower
in the PCI group (9% vs 27%; P<.01). On multivariate Cox proportional hazards
regression analysis, PCI was associated with lower MACE (hazard ratio, 0.5; 95%
confidence interval, 0.27-0.95; P=.03). CONCLUSION: Revascularization for
patients with gray-zone FFR was associated with a significantly reduced risk of
MACE compared with medical therapy alone.
PMID- 28420803
TI - Comparison of the American College of Cardiology/American Heart Association and
the European Society of Cardiology Guidelines for the Management of Patients With
Valvular Heart Disease.
AB - BACKGROUND: The American College of Cardiology/American Heart Association
(ACC/AHA) and the European Society of Cardiology (ESC) have developed guidelines
to assist clinicians in making evidence-based decisions. This study compares the
ACC/AHA and ESC guidelines for the management of patients with valvular heart
disease (VHD). METHODS: The current ACC/AHA and ESC guidelines for VHD, last
updated in 2014 and 2012, respectively, were compared by class of recommendation
(COR), level of evidence (LOE), and content. RESULTS: The ACC/AHA and ESC VHD
guidelines contain 229 and 85 recommendations, respectively. The COR
distributions of the ACC/AHA and ESC VHD guidelines were 47.6% vs 44.7% class I
[P=.65]; 46.3% vs 55.3% class II [P=.16]; and 6.1% vs 0.0% class III [P=.01],
respectively. The LOE distributions were 3.1% vs 0.0% LOE A [P=.20]; 47.2% vs
10.6% LOE B [P<.001]; and 49.8% vs 89.4% LOE C [P<.001], respectively. The
recommendation type distributions were 31.0% vs 2.4% diagnostic [P<.001]; 23.1%
vs 16.5% medical therapy [P=.20]; and 45.9% vs 81.2% interventional/surgical
recommendations [P<.001], respectively. The content of the guidelines was
similar, with only minor differences in a few recommendations. CONCLUSIONS: The
ACC/AHA VHD guidelines contain significantly more recommendations. The
distribution of COR was similar, but the ACC/AHA guidelines included more LOE B
recommendations and fewer LOE C recommendations, suggesting that the ACC/AHA
guidelines place greater emphasis on published data than expert opinion. Overall,
the ACC/AHA and ESC guidelines provide similar recommendations, suggesting
consistency in practice; however, the relative paucity of LOE A recommendations
highlights the need for additional research.
PMID- 28420804
TI - Contemporary Trends and Outcomes Associated With the Preprocedural Use of Oral
P2Y12 Inhibitors in Patients Undergoing Percutaneous Coronary Intervention:
Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
(BMC2).
AB - OBJECTIVES: We sought to describe trends in the use of preprocedural P2Y12
inhibitors and their clinical impact in patients undergoing percutaneous coronary
intervention (PCI). BACKGROUND: Oral P2Y12 inhibitors are ubiquitously used
medications; however, the specific timing of initial P2Y12 inhibitor
administration remains intensely debated. METHODS: Our study population comprised
74,053 consecutive patients undergoing PCI at 47 hospitals in Michigan from
January 2013 through June 2015. In-hospital outcomes included stent thrombosis,
bleeding, need for transfusion, and death. Hierarchical logistic regression,
propensity matching, and targeted maximum likelihood estimation were used to
adjust for baseline patient differences and clustering, and to minimize bias.
RESULTS: Of 24,733 patients who received a preprocedural P2Y12 inhibitor, 82%
received clopidogrel, 8% prasugrel, and 10% ticagrelor. Preprocedural
administration of P2Y12 inhibitors declined during the study (49.3% to 24.8%;
P<.001), and varied greatly across hospitals (14.5%-95.9%). No significant
differences in outcomes were observed between patients receiving preprocedural
clopidogrel and a matched cohort of those not receiving any preprocedural P2Y12
inhibitor (stent thrombosis: adjusted odds ratio [OR], 1.55; 95% confidence
interval [CI], 0.30-7.84; bleeding: OR, 0.96; 95% CI, 0.63-1.46; transfusion: OR,
1.03; 95% CI, 0.69-1.55; and death: OR, 0.95; 95% CI, 0.38-2.37). Similar
findings were demonstrated for preprocedural ticagrelor and prasugrel. Results
from a subgroup analysis of patients with non-ST segment elevation acute coronary
syndrome (n = 28,072) were consistent with the overall findings. CONCLUSIONS:
There was a substantial decline in the rate of preprocedural P2Y12 inhibitor
administration during the study. Furthermore, there were no significant
differences in outcomes between patients treated with preprocedural P2Y12
inhibitors and those who were not.
PMID- 28420805
TI - Immunotherapeutic approaches for hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the
fact that the diagnosis usually occurs at anadvanced stage. Even in case of
curative surgical treatment, recurrence is common. Sorafenib and regorafenib are
the only therapeutic agents that have been demonstrated to be effective in
advanced HCC, thus novel curative approaches are urgently needed. Recent studies
focus on the role of immune system in HCC. In fact, the unique immune response in
the liver favors tolerance, which can represent a real challenge for conventional
immunotherapy in these patients. Spontaneous immune responses against tumor
antigens have been detected, and new immune therapies are under investigation:
dendritic cell vaccination, immune-modulator strategy, and immune checkpoint
inhibition. In recent years different clinical trials examining the use of
immunotherapy to treat HCC have been conducted with initial promising results.
This review article will summarize the literature data concerning the potential
immunotherapeutic approaches in HCC patients.
PMID- 28420806
TI - The association of occupational metals exposure and oxidative damage, telomere
shortening in fitness equipments manufacturing workers.
AB - The welding is the major working process in fitness equipment manufacturing
industry, and International Agency for Research on Cancer has classified welding
fumes as possibly carcinogenic to humans (Group 2B). The present study aimed to
evaluate associations between the occupational exposure of metals and oxidative
damage and telomere length shortening in workers involved in the manufacture of
fitness equipment. The blood metal concentrations were monitored and
malondialdehyde (MDA), alkaline Comet assay was determined as oxidative damage in
117 workers from two representative fitness equipment manufacturing plants. MDA
levels varied according to workers' roles at the manufacturing plants, and showed
a trend as cutting>painting>welding>administration workers. Welders had
marginally shorter average telomere lengths than the administrative workers
(p=0.058). Cr and Mn levels were significantly greater in welders than they were
in administrative workers. There were significantly positive correlations between
MDA and Cr and Mn levels, the major components of welding fume. However, the
association would be eliminated if co-metals exposure were considered
simultaneously. In future, telomere length and MDA might be potential biomarkers
for predicting cardiovascular disease in co-metals exposed workers.
PMID- 28420807
TI - Effects of modifications to the health and social sector's collective agreement
on the objective characteristics of working hours.
AB - This study aimed to evaluate the effects of an intervention on objective working
hour characteristics. The intervention involved making modifications to the
collective agreement that would limit employees' entitlement to time off as
compensation. The intervention group consisted of 493 and the control group of
2,303 health and social care shift workers, respectively. We analysed the
objective pay roll-based working-hour data for 2012-2013, which we obtained from
employers' records, using the repeated measures mixed model. The changes in
objective working-hour characteristics were small, but systematic. The
intervention had some positive effects: the amount of short recovery periods (<28
h) after the last night shift decreased from 5% to 3%, and the amount of working
weeks of over 48 h decreased from 19% to 17%. The realization of employees' shift
preferences increased from 18% to 20%. However, in contrast, consecutive work
shifts and the number of scheduled absences increased and days off decreased,
suggesting less time for recovery and thus a negative trend in shift ergonomics.
When planning shifts, nursing management should avoid regulations that promote
specific unhealthy shift characteristics, that is, consecutive work shifts and
less days off.
PMID- 28420810
TI - Brain Tumor Registry of Japan (2005-2008).
PMID- 28420811
TI - The T Allele of rs8075977 in the 5'-Flanking Region of the PEDF Gene Is
Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men.
AB - Coronary artery disease (CAD) is a multifactorial disease with a genetic
component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory,
anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received
increasing attention as a sensitive biomarker of atherosclerosis and CAD. To
explore the potential association between PEDF single nucleotide polymorphisms
(SNPs) and CAD, we performed this case-control study of consecutive elderly
Chinese Han male patients (n = 416) and age-matched male controls (n = 528)
without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD
patients (age >= 60 years) are not biologically related. A tag approach was used
to examine 100% of common variations in the PEDF gene (r2 >= 0.8, minor allele
frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB
which describes the common patterns of human DNA sequence variation and Tagger
program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs
(rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634)
were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'
flanking region, showed the significant effect on the susceptibility to CAD. The
frequency of its T allele was significantly higher in the controls (52.7%) than
that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005).
In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF
gene may be protective for CAD. Conversely, the C allele at this variation site
is associated with CAD in elderly Chinese Han men.
PMID- 28420808
TI - Sequence variations in estrogen receptor 1 and 2 genes and their association with
egg production traits in Chinese Dagu chickens.
AB - Estrogen receptors alpha (ESR1) and beta (ESR2) play central roles in
folliculogenesis and therefore in reproductive biology. In the present study, two
single nucleotide polymorphisms (SNPs) were identified in the ESR1 and ESR2 genes
using PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing.
One of the identified SNPs, a T1101C transition located within exon 4 of the ESR1
gene, was significantly associated with hen-housed egg production (HHEP) at 30,
43, 57 and 66 weeks of age (P<0.05), and egg weight (EW) at 30 weeks (P<0.05).
Another SNP, a G1755A transition leading to a non-synonymous substitution (valine
459-to-isoleucine) located within exon 8 of the ESR2 gene, was also markedly
correlated with the HHEP at 30, 43, 57 and 66 weeks of age (P<0.05), and EW at 30
weeks (P<0.05). A greater proportion of the additive variance was explained by
the SNPs for most of the associated egg production traits (>1%). Furthermore, the
results of the combined genotype-based association analysis supported the finding
that the two SNPs were associated with the traits under a study. Taken together,
our findings suggest that the two sequence variations in the ESR1 and ESR2 genes
may provide promising genetic markers for the early selection and prediction of
advantageous phenotypes in chicken breeding.
PMID- 28420812
TI - Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord
blood cells.
AB - Umbilical cord blood (UCB) has advantages over other tissues because it can be
obtained without an invasive procedure and complex processing. We explored the
availability of cryopreserved UCB cells as a source of mesenchymal stromal/stem
cells (MSCs). MSCs were successfully isolated from six of 30 UCB units (median
volume, 34.0 mL; median nucleated cell number, 4.4*108) that were processed and
cryopreserved using CP-1/human serum albumin. This isolation rate was lower than
that (57%) from non-cryopreserved UCB cells. The number of nucleated cells before
and after hydroxyethyl starch separation, UCB unit volume, and cell viability
after thawing did not significantly differ between UCB units from which MSCs were
successfully isolated and those from which they were not. When CryoSure-DEX40 was
used as a cryoprotectant, MSCs were isolated from two of ten UCB units. Logistic
regression analysis demonstrated that the cryopreservation method was not
significantly associated with the success of MSC isolation. The isolated MSCs had
a similar morphology and surface marker expression profile as bone marrow-derived
MSCs and were able to differentiate into osteogenic, adipogenic, and chondrogenic
cells. In summary, MSCs can be isolated from cryopreserved UCB cells. However,
the cryopreservation process reduces the isolation rate; therefore, freshly
donated UCB cells are preferable for the isolation of MSCs.
PMID- 28420813
TI - Establishment of cell lines from adult T-cell leukemia cells dependent on
negatively charged polymers.
AB - Growing adult T-cell leukemia/lymphoma (ATLL) cells in vitro is difficult. Here,
we examined the effects of static electricity in the culture medium on the
proliferation of ATLL cells. Six out of 10 ATLL cells did not proliferate in
vitro and thus had to be cultured in a medium containing negatively charged
polymers. In the presence of poly-gamma-glutamic acid (PGA) or chondroitin
sulfate (CDR), cell lines (HKOX3-PGA, HKOX3-CDR) were established from the same
single ATLL case using interleukin (IL)-2, IL-4, and feeder cells expressing
OX40L (OX40L+HK). Dextran sulfate inhibited growth in both HKOX3 cell lines. Both
PGA and OX40L+HK were indispensable for HKOX3-PGA growth, but HKOX3-CDR could
proliferate in the presence of CDR or OX40L+HK alone. Thus, the specific action
of each negatively charged polymer promoted the growth of specific ATLL cells in
vitro.
PMID- 28420814
TI - Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma
cells is not involved in the interaction with macrophages.
AB - Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in
brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell
leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1
in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We
previously reported that cell-cell interaction between lymphoma cells and
macrophages induces lymphoma cell proliferation. In the present study, we
investigated whether CADM1 is associated with cell-cell interaction between
several human lymphoma cell lines and macrophages.CADM1 expression was observed
in the ATLL cell lines, ATN-1, ATL-T, and ATL-35T, and in the B cell lymphoma
cell lines, TL-1, DAUDI, and SLVL, using western blotting. Significant cell-cell
interaction between macrophages and ATN-1, ATL-T, ATL-35T and MT-2, DAUDI, and
SLVL cells, as assessed by induction of cell proliferation, was observed.
Immunohistochemical analysis of human biopsy samples indicated CADM1 expression
in 10 of 14 ATLL cases; however, no case of follicular lymphoma or diffuse large
B-cell lymphoma was positive for CADM1. Finally, the interaction of macrophages
with cells of the CADM1-negative ED ATLL cell line and CADM1-transfected ED cells
was tested. However, significant cell-cell interaction between macrophage and
CADM1-transfected ED cells was not observed. We conclude that CADM1 was not
associated with cell-cell interaction between lymphoma cells and macrophages,
although CADM1 may be a useful marker of ATLL for diagnostic procedures.
PMID- 28420815
TI - Early Repolarization Pattern Predicts the Increased Risk of Ventricular
Arrhythmias in Patients With Acute Anterior ST-Segment Elevation Myocardial
Infarction - A Propensity Analysis.
AB - BACKGROUND: The association between the early repolarization pattern (ERP) and
ventricular arrhythmias in patients with ST-segment elevation myocardial
infarction (STEMI) remains uncertain. We hypothesized that ERP predicts the risk
of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) during
the acute phase of anterior STEMI.Methods and Results:We enrolled 1,460
consecutive patients with acute anterior STEMI. We identified an ERP-positive
group and a 1:6 propensity-matched ERP-negative group of 183 and 471,
respectively. Comparisons of sustained VT/VF, heart failure, major adverse
cardiovascular events and all-cause death were based on Kaplan-Meier survival
analysis and multivariable Cox proportional hazards regression with adjustment
for unmatched confounding factors. In our full matching propensity score cohorts,
there were 8 out of 28 variables not matching between the 2 groups. The Kaplan
Meier curves showed ERP increased the risk of sustained VT/VF in 30 days (log
rank test P=0.00065). Adjusted for baseline unmatched confounding risk, the Cox
hazards regression analysis showed sustained VT/VF was associated with the
present of ERP (hazard ratio=2.915, 95% CI: 1.520-5.588, P=0.001). CONCLUSIONS:
In a propensity score-adjusted cohort the presence of ERP had a multivariable
adjusted association with increased risk of sustained VT/VF in patients with
anterior STEMI in the early 30 days.
PMID- 28420817
TI - Association of Kidney Dysfunction With Asymptomatic Cerebrovascular Abnormalities
in a Japanese Population With Health Checkups.
AB - BACKGROUND: Cerebrovascular disease is a major cause of mortality and morbidity.
Chronic kidney disease (CKD) is prevalent in stroke patients. This study
evaluated the correlation between kidney dysfunction and asymptomatic findings on
carotid ultrasonography (US) and brain magnetic resonance imaging (MRI) in a
Japanese population with health checkups.Methods and Results:In total, 1,716
subjects aged 40-80 years, who received health checkups from January 1 to
December 31, 2015, were included. Common carotid artery intima-media thickness
(CCA-IMT) and carotid plaques by US, and the presence of old non-lacunar
infarctions, lacunar infarctions, white matter lesions (WMLs), cerebral
microbleeds (CMBs), and atrophy by brain MRI were evaluated. After adjusting for
cardiovascular risk factors, multiple regression analyses revealed that an eGFR
ranging from 15 to 44 mL/min/1.73 m2was independently associated with CCA plaques
and hypoechoic or heterogeneous plaques. Proteinuria was associated with CCA or
internal carotid artery plaques, the number of carotid plaques, and the presence
of old non-lacunar infarctions and CMBs. CONCLUSIONS: Decreased eGFR and
proteinuria were independent risk factors for asymptomatic abnormalities on
carotid US and brain MRI, which are surrogate markers for cerebrovascular
diseases. Evaluation of these abnormalities may be useful for prevention of
symptomatic cerebrovascular events in CKD patients.
PMID- 28420816
TI - Coronary Atherosclerotic Plaque Characteristics and Cardiovascular Risk Factors -
Insights From an Optical Coherence Tomography Study.
AB - BACKGROUND: The association between cardiovascular risk factors (CVRF) and the
risk of coronary events is widely acknowledged. Whether individual risk factors
may be associated with distinct plaque characteristics is currently unclear. We
investigated the relationship between CVRF and coronary plaque burden and
phenotype.Methods and Results:We assessed coronary atherosclerotic plaque
characteristics by optical coherence tomography in 67 patients with stable
coronary artery disease undergoing coronary angiography. The plaque burden and
the distinct plaque phenotypes were compared with regard to different CVRF.
Overall plaque burden was significantly greater in patients with diabetes
mellitus (P=0.010), prediabetes (P=0.035) and obesity (P=0.024), and correlated
with the number of CVRF (R=0.358, P=0.003). Patients with diabetes had a greater
extent of fibroatheroma (P=0.015), calcific fibroatheroma (P=0.031), thin-cap
fibroatheroma (TCFA-P=0.011) and plaque erosion (P=0.002). Obese patients showed
a greater extent of fibroatheroma (P=0.007), TCFA (P=0.015) and macrophage load
(P=0.043). The number of CVRF correlated with fibroatheroma (R=0.425, P<0.001),
calcific fibroatheroma (R=0.321, P=0.008), TCFA (R=0.347, P=0.004), macrophage
load (R=0.314, P=0.010) and erosion (R=0.271, P=0.029). In the multivariate
analysis, altered glycemic status and obesity were the only independent
predictors of TCFA (P=0.026 and P=0.046, respectively), whereas altered glycemic
status was the only independent predictor of plaque erosion (P=0.001).
CONCLUSIONS: Patients with diabetes, prediabetes and obesity show more extensive
coronary atherosclerosis and more vulnerable plaque phenotypes.
PMID- 28420818
TI - Tolvaptan, Is It a Trump to Worsening Renal Function?
PMID- 28420819
TI - Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases.
AB - Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved
fatal respiratory disease that poses a concern for a global epidemic. MERS CoV
encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro).
These proteases share in processing MERS CoV polyproteins at different sites to
yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV
3CLpro and PLpro are subject to different genetic and evolutionary influences
that shape the protein sequence, codon usage pattern, and codon usage bias.
Compositional bias is present in both proteins due to a preference for AT
nucleotides. Thymidine (T) was highly preferred at the third position of codons,
preferred and overrepresented codons in PLpro, but was replaced by guanosine (G)
in 3CLpro. Compositional constraints were important in PLpro but not in 3CLpro.
Directed mutation pressure seems to have a strong influence on 3CLpro codon
usage, which is more than 30-fold higher than that in PLpro. Translational
selection was evident with PLpro but not with 3CLpro. Both proteins are less
immunogenic by showing low CpG frequencies. Correspondence analysis reveals the
presence of 3 genetic clusters based on codon usage in PLpro and 3CLpro. Every
protein had one common cluster and 2 different clusters. As revealed by
correspondence analysis, the number of influences on codon usage are restricted
in MERS CoV 3CLpro. In contrast, PLpro is controlled by a broader range of
compositional, mutational, and other influences. This may be due to the
multifunctional protease, deubiquitination, and innate immunity suppressing
profiles of PLpro.
PMID- 28420820
TI - High insulin impaired ovarian function in early pregnant mice and the role of
autophagy in this process.
AB - Metabolic disorders, such as PCOS (polycystic ovarian syndrome) and T2DM (type 2
diabetes mellitus), are associated with menstrual dysfunction, anovulation,
infertility, and early pregnancy loss. Ovarian dysfunction is not only related to
low pregnancy rates but also to the increased risk of miscarriage. Women with
PCOS or T2DM, characterized by hyperinsulinemia, commonly experience ovarian
dysfunction. In this study, we first explored whether high insulin levels
directly affected ovarian functioning during embryo implantation. Mice in the
insulin-treated group were given a subcutaneous injection of human recombinant
insulin. After insulin treatment, serum levels of E2 (estrogen), PROG
(progesterone), LH (luteinizing hormone), and FSH (follicle-stimulating hormone)
were obviously lower, and there was a significant decrement of ovarian GDF9
(growth differentiation factor 9) mRNA. H&E (hematoxylin and eosin) staining
showed a greater number of immature follicles and less luteinization in the
insulin group. Further autophagy was studied in this process. A significant
increase of P62 (SQSTM1/Sequestosome1) and a decrease of Cathepsin B, BECN1
(Beclin 1), and ULK1 (Unc-51-like kinase 1) mRNA in ovary was found in the
insulin group. Western blot analysis showed that the expressions of LC3
(microtubule-associated protein 1 light chain 3), BECN1, and Cathepsin B proteins
in ovaries from insulin group were obviously reduced, while P62 proteins were
significantly increased. All these results illustrated that insulin could
directly impair ovarian function during embryo implantation and the imbalance of
ovarian autophagy due to insulin. Autophagy could enhance the impaired ovarian
function results from insulin.
PMID- 28420821
TI - Use of liothyronine without levothyroxine in the treatment of mild consumptive
hypothyroidism caused by hepatic hemangiomas.
AB - There have been reports of the use of levothyroxine or levothyroxine plus
liothyronine for consumptive hypothyroidism caused by hepatic hemangiomas.
Administration of levothyroxine without liothyronine can be inadequate to
maintain normal levels of both free T3 and free T4 in some patients. However,
there is no report of treatment with liothyronine plus propranolol. We herein
present a case in which we used liothyronine therapy for multifocal hepatic
hemangiomas in a Japanese patient with low free T3 and normal free T4 levels. A 2
month-old Japanese male was referred to our hospital because of jaundice.
Abdominal computed tomography showed multifocal hemangiomas in both lobes of the
liver. TSH level was elevated, free T3 level was low, free T4 level was normal,
and hypothyroidism due to hepatic hemangiomas was diagnosed. In addition to
propranolol, liothyronine was started. We used liothyronine without levothyroxine
for hypothyroidism because only free T3 level had decreased, whereas free T4
level remained in the normal range. The TSH and free T3 levels normalized in this
patient in less than 1 month. The liothyronine dose was gradually reduced with
regression of the hemangiomas, and liothyronine administration was discontinued
at the age of 5 months. At the age of 11 months, growth and neurological
development of the patient met age-specific norms, and he was euthyroid at that
time. This is the first report demonstrating the use of liothyronine with
propranolol for treatment of this type of consumptive hypothyroidism.
PMID- 28420822
TI - Re-entry and related predictors among HIV-infected clients receiving methadone
maintenance treatment in Guangdong province, China.
AB - This study examined the re-entry characteristics and related predictors among HIV
infected methadone maintenance treatment (MMT) clients in Guangdong, China. Data
on HIV-infected MMT clients was obtained from the clinic MMT registration system
in Guangdong. Of the 653 participants, only 9.0% remained in the MMT program
until the end of the study. For the drop-outs, 70.0% returned to MMT at least
once by the end of the study. Re-entry was independently associated with marital
status (ORnever married = 2.24, 95% CI: 1.02-4.93; ORmarried currently = 2.34,
95% CI: 1.05-5.22), being unemployed (OR = 1.92, 95% CI: 1.12-3.27), lower
positive percentages of urine tests (OR<40% = 4.08, 95% CI: 2.21-7.54; OR40%-80%
= 2.52, 95% CI: 1.39-4.56), higher maintenance doses (OR = 3.78, 95% CI: 2.21
7.54)and poorer MMT attendance percentages (OR<20% = 282.02, 95% CI: 62.75
1268.11; OR20-49% = 20.75, 95% CI: 10.52-40.93; OR50-79% = 6.07, 95% CI: 3.44
10.73). A higher re-entry frequency was independently associated with lower
education level (ORjunior high school = 0.49, 95% CI: 0.26-0.93), average drug
use times less than twice (OR = 0.64, 95% CI: 0.41-1.00), lower positive
percentages of urine tests (OR = 0.39, 95% CI: 0.22-0.70) and poorer percentages
of MMT attendance (OR<20% = 7.24, 95% CI: 2.99-17.55; OR20-49% = 14.30, 95% CI:
5.94-34.42; OR50-79% = 6.15, 95% CI: 2.55-14.85). Re-entry and repeated re-entry
were prevalent among HIV-infected MMT clients in Guangdong, underscoring the
urgent needs of tailored interventions and health education programs for this
population.
PMID- 28420823
TI - Listeria monocytogenes serotype 4b strains replicate in monocytes/macrophages
more than the other serotypes.
AB - We analyzed the pathogenicity of various serotypes of Listeria monocytogenes
using a Balb/c mouse intravenous injection model. The survival rates of mice
inoculated with strains NS1/2b (serotype 1/2b), NS3b (serotype 3b) and NS 4b
(serotype 4b) were 60, 63.6 and 63.6%, respectively. Although the survival rates
were similar, the bacterial growth in the liver of NS3b-infected mice was 144.5
fold higher than that in the liver of NS4b-infected mice. Histopathological
analyses suggest that the NS4b strain replicated more in monocytes/macrophages,
whereas the NS3b strain replicated more in hepatocytes. These results raise a
possibility that the serotype 4b strains replicated more in monocytes/macrophages
compared to the other serotype strains. To assess this, we isolated CD11b
positive cells from mouse livers infected with EGDe (serotype 1/2a), NS1/2b,
NS3b, NS4b and the serotype 4b strains 51414 and F17 and counted the number of
live bacteria in these cells. CD11b-positive cells from the NS4b-, 51414- and F17
infected mice possessed 24.4- to 42.7-fold higher numbers of live bacteria than
those from mice infected with EGDe and NS3b strains. These results suggest that
serotype 4b strains replicated more in monocytes/macrophages than the other
serotypes, and this may be involved in the pathogenicity of serotype 4b strains,
particularly in the dissemination of L. monocytogenes through the host body.
PMID- 28420824
TI - Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode
schizophrenia: a case report.
AB - The clinical course of schizophrenia is characterized by recurrence and
chronicity and has a large burden on society. Nevertheless, diagnosis of
schizophrenia is based only on distinctive symptoms and the disease course. Near
infrared spectroscopy (NIRS) is a useful method for measuring changes in the
hemoglobin concentration in the cortical surface area and reflects brain
function. We measured NIRS four times during the clinical course in a patient
with first-episode schizophrenia.A 17-year-old woman admitted to our hospital
because of hallucinations, delusions and appetite loss. After treatment with low
dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood
volume in the frontal region. On the basis of the clinical course of this
patient, we introduce a new point of view, namely, that NIRS findings may be
useful as a state marker that indicates the severity of schizophrenia in some
cases.
PMID- 28420825
TI - Colchicine Improves Survival, Left Ventricular Remodeling, and Chronic Cardiac
Function After Acute Myocardial Infarction.
AB - BACKGROUND: Several studies have reported that colchicine attenuated the infarct
size and inflammation in acute myocardial infarction (MI). However, the sustained
benefit of colchicine administration on survival and cardiac function after MI is
unknown. It was hypothesized that the short-term treatment with colchicine could
improve survival and cardiac function during the recovery phase of MI.Methods and
Results:MI was induced in mice by permanent ligation of the left anterior
descending coronary artery. Mice were then orally administered colchicine 0.1
mg/kg/day or vehicle from 1 h to day 7 after MI. Colchicine significantly
improved survival rate (colchicine, n=48: 89.6% vs. vehicle, n=51: 70.6%,
P<0.01), left ventricular end-diastolic diameter (5.0+/-0.2 vs. 5.6+/-0.2 mm,
P<0.05) and ejection fraction (41.5+/-2.1 vs. 23.8+/-3.1%, P<0.001), as assessed
by echocardiogram compared with vehicle at 4 weeks after MI. Heart failure
development as pulmonary edema assessed by wet/dry lung weight ratio (5.0+/-0.1
vs. 5.5+/-0.2, P<0.01) and B-type natriuretic peptide expression in the heart was
attenuated in the colchicine group at 4 weeks after MI. Histological and gene
expression analysis revealed colchicine significantly inhibited the infiltration
of neutrophils and macrophages, and attenuated the mRNA expression of pro
inflammatory cytokines and NLRP3 inflammasome components in the infarcted
myocardium at 24 h after MI. CONCLUSIONS: Short-term treatment with colchicine
successfully attenuated pro-inflammatory cytokines and NLRP3 inflammasome, and
improved cardiac function, heart failure, and survival after MI.
PMID- 28420827
TI - Relaxin and Matrix Metalloproteinase-9 in Angiotensin II-Induced Abdominal Aortic
Aneurysms.
AB - BACKGROUND: This study determined whether relaxin or matrix metalloproteinase
(MMP)-9 influences angiotensin II (AngII)-induced abdominal aortic aneurysms
(AAA).Methods and Results:Male C57BL/6 or apolipoprotein E-/-mice were infused
with AngII with or without relaxin. Relaxin did not influence AngII-induced AAA
in either mouse strain. Infusion of AngII reduced, but relaxin increased, MMP-9
mRNA in macrophages. We then determined the effects of MMP-9 deficiency on AAA in
apolipoprotein E-/-mice. MMP-9 deficiency led to AAA formation in the absence of
AngII, and augmented AngII-induced aortic rupture and AAA incidence. CONCLUSIONS:
MMP-9 deficiency augmented AngII-induced AAA.
PMID- 28420826
TI - Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor
Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.
AB - BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor)
agonist with a non-prostanoid structure. In this open-label Phase II trial, the
efficacy and safety of selexipag in Japanese patients with pulmonary arterial
hypertension (PAH) is examined.Methods and Results:Selexipag was administered at
200 MUg twice daily and titrated up to 1,600 MUg by increments of 200 MUg in 37
subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33
patients comprising the per-protocol set, the pulmonary vascular resistance (PVR;
primary endpoint) decreased from 683.2+/-237.3 to 560.3+/-238.7
dyn.s/cm5(P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD)
increased from 445.0+/-102.2 to 459.1+/-112.8 m (P=0.0324); World Health
Organization functional class improved in 4 patients (12.1%), and was maintained
in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with
selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor
antagonist. Most of the commonly reported adverse events were consistent with
those reported for other PGI2formulations. Thirty-four patients attained the
individual maximum tolerated dose (maintenance dose). CONCLUSIONS: The efficacy
and tolerability of selexipag in Japanese PAH patients was confirmed by
improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is
an efficacious treatment option for Japanese PAH patients. (Trial registration:
JAPIC Clinical Trials Information [JapicCTI-111532].).
PMID- 28420828
TI - Y-TZP zirconia regeneration firing: Microstructural and crystallographic changes
after grinding.
AB - This study evaluated microstructural and crystallographic phase changes after
grinding (G) and regeneration firing/anneling (R) of Y-TZP ceramics. Thirty five
bars (LavaTM and Ice Zirkon) were divided: Y-TZP pre-sintered, control (C),
regeneration firing (R), dry grinding (DG), dry grinding+regeneration firing
(DGR), wet grinding (WG) and wet grinding+regeneration firing (WGR). Grinding was
conducted using a diamond bur and annealing at 1,000 degrees C. The
microstructure was analyzed by SEM and the crystalline phases by X-ray
diffraction (XRD). XRD showed that pre-sintered specimens contained tetragonal
and monoclinic phases, while groups C and R showed tetragonal, cubic and
monoclinic phases. After grinding, the cubic phase was eliminated in all groups.
Annealing (DGR and WGR) resulted in only tetragonal phase. SEM showed semi
circular cracks after grinding and homogenization of particles after annealing.
After grinding, surfaces show tetragonal and monoclinic phases and R can be
assumed to be necessary prior to porcelain layering when grinding is performed.
PMID- 28420829
TI - Bonding measurement -Strength and fracture mechanics approaches.
AB - This study investigated the effect of cross-sectional areas on interfacial
fracture toughness and bond strength of bilayered dental ceramics. Zirconia core
ceramics were veneered and cut to produce specimens with three different cross
sectional areas. Additionally, monolithic specimens of glass veneer were also
prepared. The specimens were tested in tension until fracture at the interface
and reported as bond strength. Fracture surfaces were observed, and the apparent
interfacial toughness was determined from critical crack size and failure stress.
The results showed that cross-sectional area had no effect on the interfacial
toughness whereas such factor had a significant effect on interfacial bond
strength. The study revealed that cross-sectional area had no effect on the
interfacial toughness, but had a significant effect on interfacial bond strength.
The interfacial toughness may be a more reliable indicator for interfacial bond
quality than interfacial bond strength.
PMID- 28420831
TI - Enamel microcracks in terms of orthodontic treatment: A novel method for their
detection and evaluation.
AB - The study aimed at introducing current available techniques for enamel
microcracks (EMCs) detection, and presenting a method for direct quantitative
analysis of an individual EMC. Measurements of the detailed EMCs characteristics
(location, length, and width) were taken from the reconstructed images of the
buccal tooth surface (teeth extracted from two age groups of patients) employing
a scanning electron microscopy (SEM) and our derived formulas before and after
ceramic brackets removal. Measured parameters of EMCs for younger age group were
2.41 um (width), 3.68 mm (length) before and 2.73 um, 3.90 mm after debonding;
for older -4.03 um, 4.35 mm before and 4.80 um, 4.37 mm after brackets removal.
Following debonding EMCs increased for both groups, however the changes in width
and length were statistically insignificant. Regardless of the age group,
proposed method enabled precise detection of the same EMC before and after
debonding, and quantitative examination of its characteristics.
PMID- 28420830
TI - Antimicrobial and antibiofilm activities of MTA supplemented with bismuth
lipophilic nanoparticles.
AB - The objective of this work was to determine the antimicrobial and antibiofilm
properties of mineral trioxide aggregate (MTA) supplemented with bismuth
lipophilic nanoparticles (BisBAL NPs). The antimicrobial activity of the
composite MTA-BisBAL NPs was determined by the disk diffusion assay, while
antibiofilm activity was analyzed by fluorescence microscopy. The cytotoxicity of
MTA-BisBAL NPs was determined on human gingival fibroblasts by optical microscopy
and crystal violet staining. MTA-BisBAL NPs inhibited the growth of Enterococcus
faecalis, Escherichia coli, and Candida albicans and also detached the biofilm of
fluorescent E. faecalis after 24 h of treatment. The addition of BisBAL
nanoparticles did not significantly modify the physical properties of MTA, and
cytotoxicity was not observed when MTA-BisBAL NPs was added on human gingival
fibroblasts. Altogether these results suggest that BisBAL nanoparticles provide
antimicrobial and antibiofilm activities to MTA while it retained their
biophysical properties without cause side effects on human gingival fibroblasts.
PMID- 28420832
TI - Effect of air-particle pressures on the surface topography and bond strengths of
resin cement to the hybrid ceramics.
AB - This study aimed to determine the appropriate pressure for airborne-abrasion by
comparing the shear bond strength values for different hybrid ceramic surfaces.
Two materials were used to produce hybrid ceramic specimens: Lava Ultimate and
MAZIC Duro. The group of specimens whose surfaces were not subjected to airborne
abrasion was set as the control group. In the experimental group, airborne
abrasion was performed at pressures of 0.1, 0.2, and 0.3 MPa. After the adhesive
and resin cement was applied, an SBS test was performed. For the MAZIC Duro
block, the SBS increased monotonically with the airborne-abrasion pressure
increased, peaking at 0.3 MPa. For the Lava Ultimate block, the SBS increased as
the airborne-abrasion pressure increased to 0.2 MPa, and then decreased in the
0.3-MPa group, thereby peaking at 0.2 MPa. This study has confirmed that the
bonding strength varies with the material used even when applying the same
surface treatment.
PMID- 28420833
TI - Correlations among bending test methods for dental hard resins.
AB - Three types of bending tests -the 3-point bending test, 4-point bending test and
biaxial flexural test- were performed to examine the correlations among the
testing methods for dental hard resins (HRs). The results for 5 HRs showed that
the bending strengths in descending order were: biaxial flexural strength>3-point
bending strength>4-point bending strength. Regression analysis of the test
methods indicated that the coefficients of determination were large for all test
methods; the largest was for the combination of the 4-point bending test and
biaxial flexural tests. The Weibull moduli ranged from 5.42 to 10.61, and a
similar descending-order trend was found in the Weibull characteristic strength
(S0) of the test methods. The biaxial flexural test method is thus a valid test
of the flexural strength of dental hard resins.
PMID- 28420834
TI - Improving the efficacy of chlorhexidine-releasing elastomerics using a layer-by
layer coating technique.
AB - The aims of this study were to identify the optimal concentration of coated
orthodontic elastomerics using a layer-by-layer technique that can release
chlorhexidine (CHX) as an antimicrobial material, and to measure the physical
properties and antimicrobial effects of the coated elastomerics. Ethyl cellulose
(EC) was used as the polymer, and five study groups with various combinations of
solvents (i.e., ethanol and dichloromethane [DCM]) were included. The coated
elastomerics were evaluated with a spectrophotometer to confirm the release of
CHX, and their surfaces were observed by SEM. The CHX+EC+DCM group sustained
antimicrobial release for the longest period (168 h, p<0.001) and exhibited the
largest antimicrobial effect in an inhibition zone test using S. mutans for 7
days (p<0.05). This group had most effective physical properties and
antimicrobial effects of coated elastomerics produced using a layerby-layer
technique, and so its composition should be considered for use in clinical
applications in orthodontics.
PMID- 28420835
TI - Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese
Patients with Type 2 Diabetes Mellitus: The Dogo Study.
AB - Objective Macrovascular diseases and urgency incontinence are common among
Japanese patients with type 2 diabetes mellitus. However, little evidence exists
regarding the association between stroke and urgency incontinence among patients
with type 2 diabetes mellitus. We examined the associations between macrovascular
complications and urgency incontinence among Japanese patients with type 2
diabetes mellitus. Methods The study subjects were 818 Japanese patients with
type 2 diabetes mellitus. Urgency incontinence was defined as present when a
subject answered "once a week or more" to the question: "Within one week, how
often do you leak urine because you cannot defer the sudden desire to urinate?"
We adjusted our analyses for sex, age, body mass index, duration of type 2
diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated
hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral
neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was
independently positively associated with urgency incontinence, with an adjusted
odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between
ischemic heart disease or peripheral artery disease and the prevalence of urgency
incontinence were not significant. Conclusion In Japanese patients with type 2
diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery
disease, was independently positively associated with urgency incontinence.
PMID- 28420836
TI - High Detection Rates of Urine Mycobacterium tuberculosis in Patients with
Suspected Miliary Tuberculosis.
AB - Objective The utility of detecting Mycobacterium tuberculosis in urine samples
from patients with pulmonary tuberculous with diffuse small nodular shadows
(suspected miliary tuberculosis (MTB)) is still unclear in Japan. A retrospective
cross-sectional study was conducted to investigate the detection rates of M.
tuberculosis in urine of patients with suspected MTB. Methods Among 687
hospitalized patients with tuberculosis, 45 with culture-confirmed suspected MTB
and the data of culture and polymerase chain reaction (PCR) for M. tuberculosis
in urine and sputum samples were investigated. The detection rates of M.
tuberculosis in urine using cultures and PCR were calculated. The detection rate
of urine was then compared with that of bone marrow aspiration. Results Fourteen
patients with suspected MTB were ultimately analyzed. A diagnosis of miliary
tuberculosis was suspected in all patients before anti-tuberculosis chemotherapy.
Positive results by PCR (11 [78.6%] cases) and culture (8 [57.1%]) were obtained
from urine samples. In patients with suspected MTB, there was no significant
difference in the detection rates between M. tuberculosis in urine using a
combination of PCR and culture (85.6% [12/14 cases]) and bone marrow aspiration
(66.7% [8/12 cases]) (p>0.05). Conclusion Using PCR and culture, we demonstrated
high detection rates of M. tuberculosis in the urine of patients with suspected
MTB. A combination of PCR and culture compared favorably with the detection rates
achieved with bone marrow aspiration. We believe that detection of M.
tuberculosis from urine and sputum samples may be easy and safe for patients with
disseminated tuberculosis infections such as definitive MTB.
PMID- 28420837
TI - Clinical Characteristics of Rheumatoid Arthritis Patients Achieving Functional
Remission with Six Months of Biological DMARDs Treatment.
AB - Objective Although previous studies have reported the prognostic factors for
functional remission, no reports have cited the predictive factors. Our aim was
to study the predictive factors for functional remission, which is a treatment
goal in rheumatoid arthritis (RA), after receiving biological disease-modifying
antirheumatic drugs (bDMARDs) treatment for six months. Methods The study
consisted of 333 RA patients treated with bDMARDs for six months. The following
patient characteristics were investigated: age, gender, disease duration, type of
bDMARDs, baseline steroid and methotrexate dosage, and levels of serum rheumatoid
factor, matrix metalloprotease, anti-cyclic citrullinated peptides antibody,
tumor necrosis factor-alpha, and interleukin-6. In our evaluation, we used the
Simplified Disease Activity Index (SDAI) for RA disease activity, health
assessment questionnaire disability index (HAQ-DI) for activity of daily living,
Short Form (SF)-36 for quality of life, and Hamilton Depression Rating Scale (HAM
D) or Self-rating Depression Scale (SDS) to determine the patients' depression
status. The subjects were divided into two groups: patients with HAQ-DI<=0.5 and
HAQ-DI>0.5 at 6 months. Results A univariate analysis comparing a group of RA
patients without functional remission (n=68) showed that the patients with
functional remission (n=164) had the following in common compared with those
without remission: younger age, shorter disease duration, lower baseline steroid
dosage, lower SDAI, lower HAQ-DI, higher SF-36, and lower HAM-D. Only lower HAQ
DI scores and "mental health" score on the SF-36 were detected using a logistic
regression analysis. Conclusion These findings suggested that RA patients with
lower HAQ-DI and lower depression scores at baseline were more likely to achieve
functional remission using bDMARDs treatment than those without these variables.
PMID- 28420839
TI - Solitary Gastric Metastasis from a Stage IA Serous Ovarian Carcinoma: A Case
Report with Literature Review.
AB - Gastric metastasis from ovarian cancer is exceptionally rare and generally occurs
in advanced stages. A 71-year-old woman presented with a solitary gastric
submucosal mass 8 years after the diagnosis of a stage IA ovarian serous
adenocarcinoma. Endoscopy showed a tumor covered with normal gastric mucosa.
Initially, a gastrointestinal stromal tumor was suspected, but biopsy revealed a
histology of invasive micropapillary carcinoma, similar to the histological
findings of the previously resected ovarian tumor. Clinicians should consider
that in patients with a submucosal tumor and a history of ovarian cancer, gastric
lesions may be secondary metastases from ovarian cancer.
PMID- 28420838
TI - Factors Associated with Pneumonia-caused Death in Older Adults with Autopsy
confirmed Dementia.
AB - Objective A better understanding of risk factors for pneumonia-caused death may
help to improve the clinical management of dementia. Methods A retrospective
observational study was conducted by reviewing the medical charts and autopsy
reports of 204 patients who were admitted to hospital, underwent a post-mortem
examination, and who were neuropathologically diagnosed with dementia. The risk
factors for pneumonia-caused death were examined both as underlying and immediate
causes of death using logistic regression models. Results A high frequency of
pneumonia-caused death was observed both in underlying- (37.3%) and immediate-
(44.1%) cause of death, but varied according to the subtypes of dementia. The
factors related to pneumonia-caused death (underlying) were subtypes of dementia;
Alzheimer's disease (odds ratio [OR], 2.891; 95% confidence interval [CI], 1.459
5.730); argyrophilic grain disease (OR, 3.148; 95% CI, 0.937-10.577); and
progressive supranuclear palsy (OR, 34.921; 95% CI, 3.826-318.775), dysphagia
(OR, 2.045; 95% CI, 1.047-3.994), diabetes mellitus (OR, 3.084; 95% CI, 1.180
8.061) and conversely related with heart failure (OR, 0.149; 95% CI, 0.026
0.861). Factors relating to pneumonia-caused death (immediate) were incidence of
pneumonia during hospitalizations (OR, 32.579; 95%CI, 4.308-246.370), gender-male
(OR, 2.060; 95% CI, 1.098-3.864), and conversely related with malignant neoplasm
(OR, 0.220; 95% CI, 0.058-0.840). Conclusion The different factors relating to
the pneumonia-caused death were evaluated depending on whether pneumonia was the
underlying- or immediate-cause of death. Strengthening clinical management on
dysphagia and diabetes mellitus, and preventing incidence of pneumonia during
hospitalization appear to be the important for the terminal stage of hospitalized
patients with dementia.
PMID- 28420840
TI - Successful Long-term Management with a Single Administration of Tri-weekly Nab
paclitaxel in a Patient with Advanced Gastric Cancer with Peritoneal
Dissemination.
AB - Nanoparticle albumin-bound (nab)-paclitaxel has shown promising activity in
advanced gastric cancer treatment. We herein report a case of advanced gastric
cancer involving long-term management with a single administration of nab
paclitaxel. A 71-year-old man diagnosed with advanced gastric cancer with
malignant ascites was treated with nab-paclitaxel as a second-line chemotherapy.
He refused treatment continuation because of various severe toxicities in the
first treatment cycle; he was therefore followed-up without any further
treatments. Despite this, no disease progression was observed over 9 months.
After progression, he received dose-dense paclitaxel, but he did not respond to
this treatment and eventually died.
PMID- 28420841
TI - Tranexamic Acid Controlled Chronic Disseminated Intravascular Coagulation
Associated with Aortic Dissection and Patent False Lumen for Three Years.
AB - The management of chronic disseminated intravascular coagulation (DIC) caused by
aortic dissection has not yet been established. Even in cases where surgical
correction is performed, therapeutic control of systemic hemorrhaging is still
required. We herein report the successful treatment of a case of aortic
dissection with a patent false lumen using tranexamic acid for acute exacerbation
of chronic DIC. Oral administration of 1,500 mg tranexamic acid per day
stabilized the coagulative and fibrinolytic parameters and relieved bleeding
tendencies with no side effects. Heparin was administered periodically for the
management of hemodialysis. This favorable result continued for up to 3 years.
PMID- 28420842
TI - The Development of Marked Collateral Circulation due to Inferior Vena Cava Filter
Occlusion in a Patient with Chronic Thromboembolic Pulmonary Hypertension
Complicated with Anti-phospholipid Syndrome.
AB - A 30-year-old Japanese man was diagnosed with chronic thromboembolic pulmonary
hypertension (CTEPH) with lupus anticoagulants (LAs) in 2003. He underwent
pulmonary endarterectomy after the placement of an inferior vena cava filter
(IVCF) in 2004, and treatment with warfarin was continued. In 2014, IVCF
occlusion and marked collateral circulation were noted during an examination for
transient dyspnea; however, his warfarin level was within the therapeutic range
for 88.9% of the time from 2003 to 2014. We herein report a rare case of CTEPH
and LAs with IVCF occlusion; in such cases, intense treatment may be required.
PMID- 28420843
TI - Rosai-Dorfman Disease of the Lung Overlapping with IgG4-related Disease: The
Difficulty in Its Differential Diagnosis.
AB - We herein report a case of Rosai-Dorfman disease (RDD) overlapping with IgG4
related disease (IgG4-RD), which presented as diffuse interstitial lung disease
with a perilymphatic pattern, followed by submandibular gland and eyelid
swelling. The pathological findings of the submandibular gland biopsy specimen
were indicative of IgG4-RD alone. We diagnosed the patient with RDD with
overlapping IgG4-RD. However, the optimal method for differentiating between
these two entities is still controversial. It is important that clinicians are
aware that RDD should be included in the differential diagnoses of diffuse
interstitial lung disease with a perilymphatic pattern and that RDD can overlap
with IgG4-RD.
PMID- 28420844
TI - Protein-losing Enteropathy Caused by Intestinal or Colonic Lymphangiectasia
Complicated by Sporadic Lymphangioleiomyomatosis: A Report of Two Cases.
AB - This report describes two patients with sporadic lymphangioleiomyomatosis
complicated by protein-losing enteropathy (PLE). Imaging studies indicated
retroperitoneal lymphangioleiomyomas and abnormalities of the adjacent digestive
tract. Endoscopic mucosal biopsy revealed colonic lymphangiectasia in one
patient; whereas the site in the other patient was intestinal. Treatment with
sirolimus led to the complete resolution of PLE within several months;
additionally, marked shrinkage was observed in the lymphangioleiomyomas of both
cases. These findings suggest that colonic or intestinal lymphatic congestion due
to neighboring lymphangioleiomyomas was the mechanism for the development of PLE.
At the time of writing this report, the beneficial effect of sirolimus has lasted
for more than 3 years.
PMID- 28420845
TI - Suffocation due to Thoracic Deformity Caused by Acromegaly.
AB - A 61-year-old man with gigantism and acromegaly choked and fell into a coma.
Immediate tracheal intubation resulted in a return of his consciousness. Enhanced
computed tomography indicated that the trachea and left main bronchus were
compressed by the thoracic spine and sternum. He required tracheotomy and
positive end-expiratory pressure to maintain his pulmonary function. This is the
first case of suffocation due to a thoracic deformity associated with acromegaly.
Physicians should focus on clearing the tracheal airway using computed tomography
to elucidate the anatomical relationship between the trachea and surrounding
structures in acromegalic patients suffering from dyspnea.
PMID- 28420846
TI - Intrathecal Isoniazid for Refractory Tuberculous Meningitis with Cerebral
Infarction.
AB - A 30-year-old Vietnamese woman, about 19 weeks pregnant, was admitted for acute
cerebral infarction with stenosis of the left middle cerebral artery (LMCA),
tuberculous meningitis, and miliary tuberculosis. Treatment with heparin,
quadruple anti-tuberculosis therapy, and dexamethasone afforded prompt
symptomatic improvement. However, she delivered a stillbirth, after which there
was recurrence of acute cerebral infarction with LMCA occlusion, sinus
thrombosis, and cranial base inflammation. A thrice-weekly 100 mg dose of
intrathecal isoniazid (INH) improved the signs of meningeal inflammation. The
patient was discharged ambulatory after 7 months. In refractory tuberculous
meningitis, multimodal therapy with intrathecal INH and steroids should be
considered.
PMID- 28420847
TI - The Successful Treatment of Myeloperoxidase Antineutrophil Cytoplasmic Antibody
positive Hypertrophic Pachymeningitis in Patients with the Limited Form of
Granulomatosis with Polyangiitis Using Methotrexate: Two Case Reports.
AB - Recent findings have indicated a close relationship between myeloperoxidase
antineutrophil cytoplasmic antibody (MPO-ANCA)-positive hypertrophic
pachymeningitis and the limited form of granulomatosis with polyangiitis (GPA).
In Japan, MPO-ANCA-positive hypertrophic pachymeningitis predominantly occurs in
elderly individuals. We herein describe the cases of two patients with MPO-ANCA
positive hypertrophic pachymeningitis associated with the limited form of GPA who
were successfully treated with a combination of corticosteroids and methotrexate.
Although methotrexate has been shown to be less effective than cyclophosphamide
for inducing the remission of GPA in patients with organ-threatening diseases,
its safety and efficacy may make it a useful alternative treatment modality for
patients with the limited form of GPA who show meningeal involvement.
PMID- 28420849
TI - The Effective Treatment of Lung Infection Due to Scedosporium prolificans with
Voriconazole and Surgery.
AB - Scedosporium prolificans is a fungus that has demonstrated resistance against
most currently available antifungal agents and which causes a rapidly
disseminating and potentially fatal infection. A 68-year-old woman presented with
a fever and consolidation in the lung field. Her symptoms and inflammatory
reaction did not improve despite treatment with tazobactam/piperacillin,
meropenem, and micafungin. Scedosporium prolificans was detected from the
patient's bronchial lavage fluid, and we initiated treatment with voriconazole.
Voriconazole was effective in shrinking the consolidation and suppressing the
inflammatory reaction. The residual lesion was surgically resected because of the
risk of systemic dissemination. The patient is currently alive without relapse or
dissemination.
PMID- 28420848
TI - Myositis Ossificans of the Hip Due to Pyogenic Arthritis Caused by Campylobacter
fetus Subspecies fetus.
AB - A 61-year-old woman was admitted with severe hip pain causing immobility and high
serum levels of inflammatory markers. The patient had a medical history of
diabetes. She had been scheduled to undergo right hip replacement surgery for the
treatment of osteoarthritis associated with gradually progressive pain. On
admission, an enhanced abdominal computed tomography scan showed an abnormal
increase in synovial fluid surrounding the right ilium, with piriformis muscle
calcification. Subsequent blood and specimen cultures identified Campylobacter
fetus subspecies fetus. This is a rare report of a case of myositis ossificans
followed by C. fetus pyogenic arthritis of the hip.
PMID- 28420850
TI - Alert Regarding Cisplatin-induced Severe Adverse Events in Cancer Patients with
Xeroderma Pigmentosum.
AB - Xeroderma pigmentosum (XP) is a genetic disease in which DNA repair mechanisms
are impaired. Cisplatin (CDDP) exerts cytotoxic effects by forming mainly
intrastrand DNA cross-links, and sensitivity to CDDP depends on the DNA repair
system. Several in vitro studies have suggested that treatment with CDDP may
cause enhanced adverse events as well as anti-tumor activity in cancer patients
with XP. This article is the first to describe two cancer patients with XP
showing severe adverse events following CDDP-based chemotherapy. Physicians
should pay attention when administering CDDP in cancer patients with XP.
PMID- 28420851
TI - Left Paraduodenal Hernia with Bowel Strangulation.
PMID- 28420852
TI - Pulmonary Sarcoidosis Presenting with Thin-walled Small Cysts.
PMID- 28420853
TI - Sarcomatoid Carcinoma Mimicking Malignant Mesothelioma.
PMID- 28420854
TI - Transient Splenial Lesion Following Abrupt Withdrawal of Carbamazepine.
PMID- 28420855
TI - Fasting Hypoglycemia on 18F-FDG PET/CT Scan.
PMID- 28420856
TI - Fasting plasma glucose and body mass index during the first trimester of
pregnancy as predictors of gestational diabetes mellitus in a Chinese population.
AB - This retrospective study assessed fasting plasma glucose (FPG) and body mass
index (BMI) during the first trimester of pregnancy as potential screening
indicators of later gestational diabetes mellitus (GDM). The study population
included 820 pregnant women who delivered in our hospital between 17 September
2013 and 3 March 2014. Demographics and baseline characteristics were collected
at the first antenatal visit; FPG levels were measured at 8 or 9 weeks. All
participants underwent a 75-g oral glucose tolerance test at 24-28 weeks
gestation. Multivariate logistic regression and receiver operating characteristic
curve analysis were performed to determine the diagnostic power of risk factors.
GDM was diagnosed in 20.3% of the women. There was an increased prevalence of GDM
with advancing age, parity, high FPG, and obesity, but not in women with family
predisposition. FPG (OR: 3.984; 95% CI: 2.397-6.62) and BMI (OR: 1.144; 95% CI:
1.083-1.208) were independent risk factors for later development of GDM (p<0.01).
FPG level >=4.6 mmol/L was the best threshold for predicting GDM with a
sensitivity of 53.89 and specificity of 70.90%. BMI >=23.5 kg/m2 yielded a
sensitivity of 48.5% and a specificity of 73.1% for predicting GDM. FPG and BMI
combined markedly enhanced the predictive capability for GDM (OR, 3.861; 95% CI:
2.701-5.520). High FPG or BMI in the first trimester, especially in combination,
may predict later GDM with limited accuracy and specificity in Chinese women.
PMID- 28420857
TI - Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes
insipidus in the third trimester of pregnancy.
AB - We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in
the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma
osmolality (300 mOsm/kgH2O) and low urinary osmolality (92 mOsm/kgH2O) were
observed at the admission to our hospital. Plasma arginine vasopressin (AVP)
level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality.
Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine
osmolality increased in response to desmopressin. The diagnosis of central
diabetes insipidus was made from these results. Magnetic resonance imaging (MRI)
of hypothalamic-pituitary region demonstrated a significant enlargement of the
pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti
rabphilin-3A antibodies that have been recently reported as a biomarker of
lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus
continued after delivery, suggesting that polyuria was not mainly due to
excessive vasopressinase activity or reduced renal sensitivity to AVP by
prostaglandin E2 that can cause temporal polyuria during pregnancy. We therefore
clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo
neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy.
This case suggested the usefulness of anti-rabphilin-3A antibodies for the
etiological diagnosis of central diabetes insipidus during pregnancy.
PMID- 28420858
TI - Transcriptional regulation of pancreas development and beta-cell function
[Review].
AB - A small number of cells in the adult pancreas are endocrine cells. They are
arranged in clusters called islets of Langerhans. The islets make insulin,
glucagon, and other endocrine hormones, and release them into the blood
circulation. These hormones help control the level of blood glucose. Therefore, a
dysfunction of endocrine cells in the pancreas results in impaired glucose
homeostasis, or diabetes mellitus. The pancreas is an organ that originates from
the evaginations of pancreatic progenitor cells in the epithelium of the foregut
endoderm. Pancreas organogenesis and maturation of the islets of Langerhans
occurs via a coordinated and complex interplay of transcriptional networks and
signaling molecules, which guide a stepwise and repetitive process of the
propagation of progenitor cells and their maturation, eventually resulting in a
fully functional organ. Increasing our understanding of the extrinsic, as well as
intrinsic mechanisms that control these processes should facilitate the efforts
to generate surrogate beta cells from ES or iPS cells, or to reactivate the
function of important cell types within pancreatic islets that are lost in
diabetes.
PMID- 28420859
TI - Ultrastructural and physico-chemical characterization of saliva during menstrual
cycle in perspective of ovulation in human.
AB - Human saliva is a potential diagnostic fluid and any alteration in body might be
reflected in saliva so that saliva is considered as "mirror of the body".
Variations in salivary hormone level, ultra structure, pH, flow rate, buffering
capacity and electrolytes level are found during menstrual cycle in regard to
ovulation. Thirty healthy volunteers were used for the assessment of physico
chemical changes in saliva. Reproductive cycle was categorized as pre-ovulation
phase (5 to 12 days), ovulation phase (13 or 14 days) and post-ovulation phase
(15 to 25 days) according to salivary arborization test and hormonal analysis.
Estradiol and luteinizing hormone was gradually increased and attained peak at
the level of 2.28 +/- 0.20 pg/mL and 1.35 +/- 0.41 mIU/mL respectively during the
ovulation phase. The electrolytes result clearly indicates that the influx of
common electrolytes is important for crystallization and help to induce clear
ferning pattern in ovulation phase. Sodium (Na) and chloride (Cl) were found to
be high during ovulation phase only. Average salivary pH was 7.5, 7.1, and 7.3
during ovulation, pre- and post-ovulation phases respectively. Buffering capacity
of saliva was normal during pre- and post- ovulation phases. In contrast, in
ovulation phase the buffer capacity was slightly higher. At the first time, the
scanning electron microscopy (SEM) studies revealed the ultra structure
difference of saliva during menstrual cycle. During ovulation phase a compact
network-shaped mesh was appeared; such structure was not appeared in pre- and
post ovulation phases. Additionally, we observed the saliva is arrayed as a fine
mosaic-like structure during ovulation. Based on physico-chemical properties and
hormonal levels may lead to develop a detection kit/sensor for detecting the
ovulation phase in human.
PMID- 28420861
TI - Potential proteins targeted by let-7f-5p in HeLa cells.
AB - MicroRNAs are a class of small, endogenous, non-coding RNAs mediating
posttranscriptional gene silencing. The current authors hypothesized that let-7f
5p is likely involved in cell invasion and proliferation by regulating the
expression of target genes. The current study combined let-7f-5p with iTRAQ to
assess its effect on gene expression in HeLa cells. Results indicated that 164
proteins were expressed at different levels in HeLa cells overexpressing let-7f
5p and negative controls and that 172 proteins were expressed at different levels
in let-7f-5p-silenced HeLa cells and negative controls. Results indicated that
let-7f-5p may suppress insulin-like growth factor 2 mRNA binding protein 1
(IGF2BP1) in HeLa cells.
PMID- 28420860
TI - Comparison of the docetaxel concentration in human plasma measured with liquid
chromatography-tandem mass spectrometry (LC-MS/MS) and a nanoparticle immunoassay
and clinical applications of that assay.
AB - To determine the feasibility of using a nanoparticle immunoassay for clinical
therapeutic drug monitoring (TDM) of docetaxel concentrations, a sensitive and
simple method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
established to measure the docetaxel concentration in human plasma and the
results of LC-MS/MS and the immunoassay were compared. Docetaxel and paclitaxel
(the internal standard, or IS) in human plasma were extracted through protein
precipitation, separated on a Diamonsil C18 column (150 mm * 4.6 mm, 5 MUm),
ionized with positive ions, and detected with LC-MS/MS in multi-reaction
monitoring (MRM) mode. Plasma samples from 248 cancer patients were assayed with
LC-MS/MS and a nanoparticle immunoassay. Data from the samples were analyzed with
the statistical software SPSS and the software MedCalc. Results indicated that
the calibration curve of the validated method of LC-MS/MS was linear over the
range of 10-2,000 ng/mL, with an lowest limit of quantitation (LLOQ) of 10 ng/mL,
and the intra- and inter- day precision and accuracy were both < +/- 15%.
Comparison of the two methods indicated that results of the LC-MS/MS were closely
related to those of the nanoparticle immunoassay, with a correlation coefficient
(R) of 0.965 and acceptable 95% confidence intervals (CI) of - 231.7-331.1 ng/mL.
Overall, the established method of LC-MC/MS and the nanoparticle immunoassay were
both suitable for measurement of the docetaxel concentration in human plasma, and
the immunoassay was far more cost-effective and better at clinical TDM of
docetaxel in clinical practice.
PMID- 28420862
TI - Clinical characteristics, treatment, and prognosis of patients with ischemic and
nonischemic acute severe heart failure. Analysis of data from the COMMIT-AHF
registry.
AB - INTRODUCTION There are limited data on the impact of ischemic etiology on the
clinical status and long-term prognosis of patients with acute severe heart
failure (HF) not associated with acute coronary syndrome (ACS). OBJECTIVES The
aim of this study was to assess the clinical characteristics, treatment, and 12
month mortality of patients with acute severe HF not associated with ACS,
according to the etiology of HF. PATIENTS AND METHODS Data from 112 patients
with acute severe HF not associated with ACS were analyzed: 61 patients with
ischemic HF and 51 patients with nonischemic HF. Acute severe HF was defined as
acute HF on admission with at least one of the following characteristics:
pulmonary congestion, cardiogenic shock, catecholamine or intraaortic balloon
pump support, ultrafiltration, mechanical ventilation, prolonged use of
intravenous diuretics, fluid in the body cavities requiring decompression, or
multiorgan failure. RESULTS Patients with ischemic HF were older (62 vs 54 years,
P = 0.001), predominately male (84% vs 65%, P = 0.02), had more comorbidities,
and had lower left ventricular ejection fraction (21% vs 27%, P = 0.02). There
were no significant differences in treatment modalities (ie, mechanical
ventilation, hemodiafiltration, intraaortic balloon pump, left ventricular assist
device, heart transplantation), except for 14 percutaneous coronary interventions
in the ischemic group. In-hospital adverse events were similar between the
groups. Among 83 discharged patients with available follow-up, death was reported
for 15 patients with ischemic and 11 patients with nonischemic HF (34% vs 28%, P
= 0.42). CONCLUSIONS Ischemic HF, accounting for approximately half of the cases
of acute severe HF not related to ACS, was not associated with a significantly
worse prognosis than nonischemic HF.
PMID- 28420863
TI - Changes in systemic immune response after stereotactic ablative radiotherapy.
Preliminary results of a prospective study in patients with early lung cancer.
AB - INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common lung tumor.
Conventional conservative treatment in medically inoperable patients with early
stage NSCLC has poor outcome. To improve treatment efficacy, stereotactic
ablative radiotherapy (SABR) has been developed, which enables the delivery of
high-dose radiation to the tumor. OBJECTIVES This prospective study was
conducted to test the hypothesis that a sudden death of cancer cells after SABR
may lead to changes in systemic immune response. PATIENTS AND METHODS We
enrolled 89 treatment-naive patients with stage T1/2aN0 NSCLC. All patients
received SABR, in accordance with treatment standards at our department. Blood
samples were collected 3 times: before treatment (n = 89), and then at 2 (n = 86)
and 12 weeks (n = 75) after treatment completion to assess the proportion of
CD4(+) and CD8(+) T cells, and the expression of T-lymphocyte transcription
factors: T-bet, GATA-3, ROR-gammat, and FoxP3. Serum C-reactive protein (CRP)
levels, absolute neutrophil count (ANC), absolute lymphocyte count, and white
blood cell (WBC) count were measured to exclude the impact of nonspecific
inflammatory reaction. The expression levels of lymphocyte antigens were measured
by flow cytometry. RESULTS Serum CRP levels, ANC, and WBC count remained
stable during the study. We observed slight lymphopenia, which correlated with
irradiated lung volume. After SABR, the proportion of CD8(+), CD4(+), as well as
the proportion of CD4(+) T cells expressing GATA-3(+), T-bet(+), or ROR-gammat(+)
increased, while the number of CD4(+)FoxP3(+) cells (specific for regulatory T
cells) decreased. CONCLUSIONS Our findings may suggest that SABR enhances the
systemic immune response by increasing the proportion of proinflammatory T-cell
subpopulations.
PMID- 28420865
TI - A Novel Variant t(1;22) Translocation - ins(22;1)(q13;p13p31) - in a Child with
Acute Megakaryoblastic Leukemia.
AB - BACKGROUND The reciprocal translocation t(1;22)(p13;q13) involving the RBM15 and
MKL1 genes is an uncommon abnormality that occurs in a subset of acute myeloid
leukemia with megakaryocytic differentiation (AMKL). Variant translocations have
been infrequently described in this subtype of leukemia. CASE REPORT We describe
the case of a 3-month-old girl who presented with progressive abdominal
distension, vomiting, and fever. Although there was no morphologic evidence of
leukemia in the bone marrow, cytogenetic and metaphase fluorescence in situ
hybridization analysis identified an insertion of p13p31 bands of chromosome 1
onto the long arm of chromosome 22, resulting in the karyotype:
46,XX,ins(22;1)(q13;p13p31). Subsequent liver biopsy demonstrated extensive
involvement by AMKL. CONCLUSIONS AMKL can present with fewer than 20% blasts in
the peripheral blood or bone marrow, necessitating careful evaluation for
extramedullary disease. In other situations, bone marrow fibrosis can result in
difficult marrow aspirations and a falsely decreased blast count. This case
report highlights the critical role of careful cytogenetic and FISH testing in
the diagnosis of AMKL.
PMID- 28420864
TI - Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by
Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal
Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy.
AB - BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth
and acts as potential therapy for traumatic brain injury. This study was designed
to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem
cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs
separated from the hippocampus of rat. NSCs were divided into four groups: cells
under normoxic conditions that acted as controls (C group), cells under hypoxia
(H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia
with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the
IGF-1 receptor (HIP group). The cell viability and apoptosis were respectively
measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)
assay and flow cytometry. Finally, the phosphorylation levels of apoptosis
associated proteins and key kinases in the phosphatidylinositol-3-kinase
(PI3K)/AKT and the mitogen-activated protein kinase/extracellular signal
regulated kinase (MAPK/ERK) pathways were detected by Western blot analysis.
RESULTS In comparison with the H group, the cell viability was increased while
the cell apoptosis was reduced by IGF-1 in the HI group. Besides, the expression
levels of Bax, cytochrome c, and activated caspase-3 were all improved in the H
group, and the remarkable differences were eliminated in the HI group compared
with the C group. The expression level of Bcl-2 was the opposite. Additionally,
down-regulations of phosphorylated AKT, MAPK, and ERK induced by hypoxia were all
improved by IGF-1. All the influences of IGF-1 were weakened by addition of PPP.
CONCLUSIONS IGF-1 increased cell viability while decreasing apoptosis in hypoxic
NSCs through the PI3K/AKT and MAPK/ERK pathways.
PMID- 28420866
TI - Male New Zealand robins (Petroica longipes) cater to their mate's desire when
sharing food in the wild.
AB - In many species that have bi-parental care, food-sharing males provide vital
nutritional resources to their mates during reproduction. However, it is
currently unknown whether females can signal specific desires to their mates, or
if males can cater to female desire in the wild. Here we investigate whether and
how wild male North Island robins (Petroica longipes) respond to changes in their
mates' desires and nutritional need when sharing food. We demonstrate that wild
female robins' desire for particular foods changes over short time periods; when
given the choice between two types of insect larvae, females prefer the type they
have not recently eaten. In our experiments, wild male robins preferentially
shared the larvae type that their mate was most likely to desire and also
increased the quantity of food shared if she had begun incubating. Males catered
to their mates' desire when female behaviour was the only cue available to guide
their choices. This is the first evidence that females may behaviourally
communicate their specific food desires to their mates, enabling males to cater
to fine-scale changes in their mates' nutritional requirements in the wild. Such
a simple behaviour-reading mechanism has the potential to be widespread among
other food-sharing species.
PMID- 28420867
TI - Interaction effects of polyfluoroalkyl substances and sex steroid hormones on
asthma among children.
AB - To evaluate the interactions between polyfluoroalkyl substances (PFASs) and
reproductive hormones and associated asthma, a total of 231 asthmatic and 225 non
asthmatic adolescents were selected from northern Taiwan in the Genetic and
Biomarkers study for Childhood Asthma from 2009-2010. The interaction between
PFASs and reproductive hormones on asthma was analyzed with a two-level binary
logistic regression model. The results showed that, among asthmatics, PFASs were
positively associated with estradiol levels and negatively associated with
testosterone levels. However, only significant association was identified for
PFNA and estradiol in control group. After controlling for hormone levels,
associations between PFAS exposure and asthma were consistently stronger among
children with higher than lower estradiol, with odds ratios (OR) for asthma
ranging from 1.25 for PFOS (95% Confidence Interval [CI]: 0.90, 1.72) to 4.01 for
PFDA (95% CI: 1.46, 11.06) among boys and 1.25 for PFOS (95% CI: 0.84, 1.86) to
4.16 for PFNA (95% CI: 1.36, 12.73) among girls. Notably, the interactions
between estradiol and PFASs were significant for PFOS (p = 0.026) and PFNA (p =
0.043) among girls. However, testosterone significantly attenuated the
association between PFOS and asthma across sex. In conclusions, our findings
suggested that reproductive hormones amplify the association between PFASs and
asthma among adolescents.
PMID- 28420868
TI - Aurachin SS, a new antibiotic from Streptomyces sp. NA04227.
PMID- 28420869
TI - Verification of oligomycin A structure: synthesis and biological evaluation of 33
dehydrooligomycin A.
AB - Although, the structure of oligomycin A (1) was confirmed by spectroscopic and
chemical evaluations, some crystallographic data cast doubt on the originally
adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was
suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1
propenyl). To clarify this matter we synthesized and evaluated 33
dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O
mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin
(2) and results of quantum chemical calculations have shown that this derivative
exists in the keto rather than in the enol tautomer 2a. The in vitro
antimicrobial activity of 2 was approximately two times weaker in comparison with
oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp.
strains and similar activity against certain filamentous fungi. The docking
binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding
affinity for 2 when compared with oligomycin A; that correlated with its activity
against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in
vitro antiproliferative activities of 2 are also discussed.
PMID- 28420870
TI - Time-Resolved Visual Chiral Discrimination of Cysteine Using Unmodified CdTe
Quantum Dots.
AB - Herein, we demonstrate a simple yet novel luminescence assay for visual chiral
discrimination of cysteine. Thioglycolic acid (TGA)-capped cadmium-telluride
(CdTe) quantum dots (QDs) exposing green emission were directly synthesized in
aqueous solution. The interaction between cysteine molecules and CdTe QDs induced
the aggregation of QDs via hydrogen bonding. As a result of electronic coupling
within these aggregates, a redshift both in the absorption and emission spectra
of QDs occured. The difference in the kinetics of the interactions between L- and
D-cysteine with CdTe QDs led to chiral recognition of these enantiomers. Addition
of D-cysteine to CdTe QDs in a basic media caused a green-to-yellow color change,
while no color alteration in QDs emission was observed in the presence of L
cysteine after 2 hours. Notably, the QDs used in the proposed assay are free from
any labling/modification, which makes the present strategy highly attractive for
sensing applications. Furthermore, the presented chiral assay is able to
determine the enantiomeric excess (ee) of D-cysteine in the whole range of ee
values (from -100% to 100%).
PMID- 28420871
TI - Interactive Outlining of Pancreatic Cancer Liver Metastases in Ultrasound Images.
AB - Ultrasound (US) is the most commonly used liver imaging modality worldwide. Due
to its low cost, it is increasingly used in the follow-up of cancer patients with
metastases localized in the liver. In this contribution, we present the results
of an interactive segmentation approach for liver metastases in US acquisitions.
A (semi-) automatic segmentation is still very challenging because of the low
image quality and the low contrast between the metastasis and the surrounding
liver tissue. Thus, the state of the art in clinical practice is still manual
measurement and outlining of the metastases in the US images. We tackle the
problem by providing an interactive segmentation approach providing real-time
feedback of the segmentation results. The approach has been evaluated with
typical US acquisitions from the clinical routine, and the datasets consisted of
pancreatic cancer metastases. Even for difficult cases, satisfying segmentations
results could be achieved because of the interactive real-time behavior of the
approach. In total, 40 clinical images have been evaluated with our method by
comparing the results against manual ground truth segmentations. This evaluation
yielded to an average Dice Score of 85% and an average Hausdorff Distance of 13
pixels.
PMID- 28420872
TI - Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor
induced Angiogenesis via Downregulation of Osteopontin Expression.
AB - Angiogenesis plays a critical role in the progression and vulnerability of
atherosclerotic plaques; however, the orchestration of angiogenesis in
atherosclerotic plaque formation remains unclear. The results of microarray
analysis, real-time PCR and immunohistochemical analyses showed that
Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly
decreased, while that of osteopontin (OPN) was increased, in atherosclerotic
plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and
OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic
plaques. The results of an in vitro study showed that Hes-1 was downregulated,
while OPN was upregulated, in a time- and dose-dependent manner in human
umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1
knockdown was found to have transcriptional promotion effect on OPN expression in
HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary,
Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis
in vitro and in vivo. The results of this study suggest that decreased Hes-1
expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by
upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN
expression may be a promising strategy to prevent vulnerable plaque formation in
patients with atherosclerosis.
PMID- 28420873
TI - Viewing immune regulation as it happens: in vivo imaging for investigation of
regulatory T-cell function.
AB - Regulatory T cells (Tregs) play indispensable roles in the immune system, in
limiting excessive or inappropriate immune and inflammatory responses. They
achieve this function via effects on other immune cells in the secondary lymphoid
system, and in peripheral locations such as skin, gut and bone marrow. As for the
more extensively studied cellular players in the immune system, particularly
dendritic cells and conventional T cells, in vivo imaging of Tregs via two-photon
(or multiphoton) microscopy (MPM) has been central to the development of
understanding how these cells function. In this brief review, we will describe
the studies that have utilised MPM to examine Treg behaviour in vivo. These
studies have investigated Treg behaviour in lymph nodes and spleen, as well as in
peripheral organs such as skin, small intestine and bone marrow. The findings
from these experiments underline how assumptions made about Treg function based
on results of in vitro experiments are often not supported by direct
visualisation of these cells in their normal in vivo settings. Together this work
reveals that only via MPM analysis can Treg function be investigated in the
complicated multicellular environments where conventional T cells, antigen
presenting cells and other potential cellular targets of Tregs are present with
each undergoing their own specific actions.
PMID- 28420874
TI - Therapeutic targeting using tumor specific peptides inhibits long non-coding RNA
HOTAIR activity in ovarian and breast cancer.
AB - Long non-coding RNAs (lncRNAs) play key roles in human diseases, including
cancer. Functional studies of the lncRNA HOTAIR (HOX transcript antisense RNA)
provide compelling evidence for therapeutic targeting of HOTAIR in cancer, but
targeting lncRNAs in vivo has proven to be difficult. In the current study, we
describe a peptide nucleic acids (PNA)-based approach to block the ability of
HOTAIR to interact with EZH2 and subsequently inhibit HOTAIR-EZH2 activity and
resensitize resistant ovarian tumors to platinum. Treatment of HOTAIR
overexpressing ovarian and breast cancer cell lines with PNAs decreased invasion
and increased chemotherapy sensitivity. Furthermore, the mechanism of action
correlated with reduced nuclear factor-kappaB (NF-kappaB) activation and
decreased expression of NF-kappaB target genes matrix metalloprotease 9 and
interleukin 6. To deliver the anti-lncRNA to the acidic (pH approximately 6)
tumor microenvironment, PNAs were conjugated to pH-low insertion peptide (pHLIP).
Treatment of mice harboring platinum-resistant ovarian tumor xenografts with
pHLIP-PNA constructs suppressed HOTAIR activity, reduced tumor formation and
improved survival. This first report on pHLIP-PNA lncRNA targeting solid tumors
in vivo suggests a novel cancer therapeutic approach.
PMID- 28420875
TI - Down-regulation of cholinergic signaling in the habenula induces anhedonia-like
behavior.
AB - Dysfunction of cholinergic signaling in the brain has long been believed to be
associated with depressive disorders. However, the functional impact of habenular
cholinergic signaling on the specified depressive behaviors is not well
understood. Here, we demonstrated that the expression levels of cholinergic
signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated
in a chronic restraint stress (CRS) rat model of depression, in which rats
display depression-like behaviors such as anhedonia and mood despair. Moreover,
knockdown of CHAT in the rat habenula was sufficient to evoke anhedonia-like
behavior. The anhedonia-like behavior induced by CHAT knockdown was not reversed
by chronic administration of the selective serotonin reuptake inhibitor
fluoxetine. To determine whether habenular cholinergic signaling is associated
with regulation of dopamine neurons in the ventral tegmental area (VTA) and
serotonin neurons in the dorsal raphe nucleus (DRN), we used CHAT::cre transgenic
mice expressing the Designer Receptors Exclusively Activated by Designer Drugs
(DREADD). Pharmacogenetic activation of habenular cholinergic neurons induces the
excitation of dopamine neurons in the VTA and reduces the immunoreactivity of 5
hydroxytryptamine (5-HT) in the DRN. Habenular cholinergic gene down-regulation
was recapitulated in the postmortem habenula of suicide victims diagnosed with
major depressive disorder (MDD).
PMID- 28420876
TI - Examining gray matter structure associated with academic performance in a large
sample of Chinese high school students.
AB - Achievement in school is crucial for students to be able to pursue successful
careers and lead happy lives in the future. Although many psychological
attributes have been found to be associated with academic performance, the neural
substrates of academic performance remain largely unknown. Here, we investigated
the relationship between brain structure and academic performance in a large
sample of high school students via structural magnetic resonance imaging (S-MRI)
using voxel-based morphometry (VBM) approach. The whole-brain regression analyses
showed that higher academic performance was related to greater regional gray
matter density (rGMD) of the left dorsolateral prefrontal cortex (DLPFC), which
is considered a neural center at the intersection of cognitive and non-cognitive
functions. Furthermore, mediation analyses suggested that general intelligence
partially mediated the impact of the left DLPFC density on academic performance.
These results persisted even after adjusting for the effect of family
socioeconomic status (SES). In short, our findings reveal a potential
neuroanatomical marker for academic performance and highlight the role of general
intelligence in explaining the relationship between brain structure and academic
performance.
PMID- 28420877
TI - Proximate effects of temperature versus evolved intrinsic constraints for
embryonic development times among temperate and tropical songbirds.
AB - The relative importance of intrinsic constraints imposed by evolved physiological
trade-offs versus the proximate effects of temperature for interspecific
variation in embryonic development time remains unclear. Understanding this
distinction is important because slow development due to evolved trade-offs can
yield phenotypic benefits, whereas slow development from low temperature can
yield costs. We experimentally increased embryonic temperature in free-living
tropical and north temperate songbird species to test these alternatives. Warmer
temperatures consistently shortened development time without costs to embryo mass
or metabolism. However, proximate effects of temperature played an increasingly
stronger role than intrinsic constraints for development time among species with
colder natural incubation temperatures. Long development times of tropical birds
have been thought to primarily reflect evolved physiological trade-offs that
facilitate their greater longevity. In contrast, our results indicate a much
stronger role of temperature in embryonic development time than currently
thought.
PMID- 28420879
TI - Evolutionary genetics: Fantastic beasts - cephalopod RNA recoding.
PMID- 28420880
TI - Balancing Speed and Coverage by Sequential Seeding in Complex Networks.
AB - Information spreading in complex networks is often modeled as diffusing
information with certain probability from nodes that possess it to their
neighbors that do not. Information cascades are triggered when the activation of
a set of initial nodes - seeds - results in diffusion to large number of nodes.
Here, several novel approaches for seed initiation that replace the commonly used
activation of all seeds at once with a sequence of initiation stages are
introduced. Sequential strategies at later stages avoid seeding highly ranked
nodes that are already activated by diffusion active between stages. The gain
arises when a saved seed is allocated to a node difficult to reach via diffusion.
Sequential seeding and a single stage approach are compared using various seed
ranking methods and diffusion parameters on real complex networks. The
experimental results indicate that, regardless of the seed ranking method used,
sequential seeding strategies deliver better coverage than single stage seeding
in about 90% of cases. Longer seeding sequences tend to activate more nodes but
they also extend the duration of diffusion. Various variants of sequential
seeding resolve the trade-off between the coverage and speed of diffusion
differently.
PMID- 28420878
TI - Synergistic Antimicrobial Effects of Silver/Transition-metal Combinatorial
Treatments.
AB - Due to the emergence of multi-drug resistant strains, development of novel
antibiotics has become a critical issue. One promising approach is the use of
transition metals, since they exhibit rapid and significant toxicity, at low
concentrations, in prokaryotic cells. Nevertheless, one main drawback of
transition metals is their toxicity in eukaryotic cells. Here, we show that the
barriers to use them as therapeutic agents could be mitigated by combining them
with silver. We demonstrate that synergism of combinatorial treatments
(Silver/transition metals, including Zn, Co, Cd, Ni, and Cu) increases up to 8
fold their antimicrobial effect, when compared to their individual effects,
against E. coli and B. subtilis. We find that most combinatorial treatments
exhibit synergistic antimicrobial effects at low/non-toxic concentrations to
human keratinocyte cells, blast and melanoma rat cell lines. Moreover, we show
that silver/(Cu, Ni, and Zn) increase prokaryotic cell permeability at sub
inhibitory concentrations, demonstrating this to be a possible mechanism of the
synergistic behavior. Together, these results suggest that these combinatorial
treatments will play an important role in the future development of antimicrobial
agents and treatments against infections. In specific, the cytotoxicity
experiments show that the combinations have great potential in the treatment of
topical infections.
PMID- 28420881
TI - Reduced biological effect of e-cigarette aerosol compared to cigarette smoke
evaluated in vitro using normalized nicotine dose and RNA-seq-based
toxicogenomics.
AB - Electronic cigarettes (e-cigarettes) use has increased globally and could
potentially offer a lower risk alternative to cigarette smoking. Here, we
assessed the transcriptional response of a primary 3D airway model acutely
exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were
generated with standard intense smoking regimens with careful consideration for
dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions
were tested for equivalent and higher nicotine delivery compared to 3R4F. RNA was
extracted at 24 hrs and 48 hrs post exposure for RNA-seq. 873 and 205 RNAs were
differentially expressed for 3R4F smoke at 24 hrs and 48 hrs using a pFDR < 0.01
and a [fold change] > 2 threshold. 113 RNAs were differentially expressed at the
highest dose of e-cigarette aerosol using a looser threshold of pFDR < 0.05, 3
RNAs exceeded a fold change of 2. Geneset enrichment analysis revealed a clear
response from lung cancer, inflammation, and fibrosis associated genes after 3R4F
smoke exposure. Metabolic/biosynthetic processes, extracellular membrane,
apoptosis, and hypoxia were identified for e-cigarette exposures, albeit with a
lower confidence score. Based on equivalent or higher nicotine delivery, an acute
exposure to e-cigarette aerosol had a reduced impact on gene expression compared
to 3R4F smoke exposure in vitro.
PMID- 28420882
TI - The role of the SWI/SNF chromatin remodeling complex in maintaining the stemness
of glioma initiating cells.
AB - Glioma initiating cells (GICs) are thought to contribute to therapeutic
resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in
adults. Although the stem-like properties of GICs, such as self-renewal and
tumorigenicity, are epigenetically regulated, the role of a major chromatin
remodeling complex in human, the SWI/SNF complex, remains unknown in these cells.
We here demonstrate that the SWI/SNF core complex, that is associated with a
unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays
essential roles in stemness maintenance in GICs. The serum-induced
differentiation of GICs downregulated the endogenous expression of DPF1 and
DPF3a, and the shRNA-mediated knockdown of each gene reduced both sphere-forming
ability and tumor-forming activity in a mouse xenograft model. Rescue experiments
revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have
previously reported that d4-family members can function as adaptor proteins
between the SWI/SNF complex and NF-kappaB dimers, this does not significantly
contribute to maintaining the stemness properties of GICs. Instead, these
proteins were found to link a corepressor complex containing the nuclear
receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our
results indicate that DPF1 and DPF3a are potential therapeutic targets for
glioblastoma.
PMID- 28420883
TI - Leukocidins: staphylococcal bi-component pore-forming toxins find their
receptors.
AB - Staphylococcus aureus is a major bacterial pathogen that causes disease
worldwide. The emergence of strains that are resistant to commonly used
antibiotics and the failure of vaccine development have resulted in a renewed
interest in the pathophysiology of this bacterium. Staphylococcal leukocidins are
a family of bi-component pore-forming toxins that are important virulence
factors. During the past five years, cellular receptors have been identified for
all of the bi-component leukocidins. The identification of the leukocidin
receptors explains the cellular tropism and species specificity that is exhibited
by these toxins, which has important biological consequences. In this Review, we
summarize the recent discoveries that have reignited interest in these toxins and
provide an outlook for future research.
PMID- 28420884
TI - A CRISPR toolbox to study virus-host interactions.
AB - Viruses depend on their hosts to complete their replication cycles; they exploit
cellular receptors for entry and hijack cellular functions to replicate their
genome, assemble progeny virions and spread. Recently, genome-scale CRISPR-Cas
screens have been used to identify host factors that are required for virus
replication, including the replication of clinically relevant viruses such as
Zika virus, West Nile virus, dengue virus and hepatitis C virus. In this Review,
we discuss the technical aspects of genome-scale knockout screens using CRISPR
Cas technology, and we compare these screens with alternative genetic screening
technologies. The relative ease of use and reproducibility of CRISPR-Cas make it
a powerful tool for probing virus-host interactions and for identifying new
antiviral targets.
PMID- 28420886
TI - Hypertension: Hypertension in pregnancy: a risk factor for the whole family?
PMID- 28420885
TI - Oxidative stress, protein damage and repair in bacteria.
AB - Oxidative damage can have a devastating effect on the structure and activity of
proteins, and may even lead to cell death. The sulfur-containing amino acids
cysteine and methionine are particularly susceptible to reactive oxygen species
(ROS) and reactive chlorine species (RCS), which can damage proteins. In this
Review, we discuss our current understanding of the reducing systems that enable
bacteria to repair oxidatively damaged cysteine and methionine residues in the
cytoplasm and in the bacterial cell envelope. We highlight the importance of
these repair systems in bacterial physiology and virulence, and we discuss
several examples of proteins that become activated by oxidation and help bacteria
to respond to oxidative stress.
PMID- 28420887
TI - Kidney cancer: Targeting metabolism in RCC.
PMID- 28420888
TI - Global gene expression profiling of healthy human brain and its application in
studying neurological disorders.
AB - Brain function is governed by precise regulation of gene expression across its
anatomically distinct structures; however, the expression patterns of genes
across hundreds of brain structures are not clearly understood. Here, we describe
a gene expression model, which is representative of the healthy human brain
transcriptome by using data from the Allen Brain Atlas. Our in-depth gene
expression profiling revealed that 84% of genes are expressed in at least one of
the 190 brain structures studied. Hierarchical clustering based on gene
expression profiles delineated brain regions into structurally tiered spatial
groups and we observed striking enrichment for region-specific processes.
Further, weighted co-expression network analysis identified 19 robust modules of
highly correlated genes enriched with functional associations for neurogenesis,
dopamine signaling, immune regulation and behavior. Also, structural distribution
maps of major neurotransmission systems in the brain were generated. Finally, we
developed a supervised classification model, which achieved 84% and 81%
accuracies for predicting autism- and Parkinson's-implicated genes, respectively,
using our expression model as a baseline. This study represents the first use of
global gene expression profiling from healthy human brain to develop a disease
gene prediction model and this generic methodology can be applied to study any
neurological disorder.
PMID- 28420889
TI - Evaluation of Urinary Stone Composition and Differentiation between Urinary
Stones and Phleboliths Using Single-source Dual-energy Computed Tomography.
AB - The aim of this study was to investigate the utility of single-source dual-energy
computed tomography (SS-DECT) composition analysis in characterizing different
types of urinary stones and differentiating them from phleboliths. This study
included 29 patients with urinary stones who were scheduled for surgery. All
patients were scanned, first using single-energy computed tomography acquisition
and then DECT acquisition on SS-DECT. Dual-energy data were archived to a
Gemstone spectral imaging (GSI) viewer (GE Healthcare, Milwaukee, WI, USA).
Hounsfield units (HU) and effective atomic numbers (Zeff) were estimated using
the GSI viewer. The results of dual-energy analysis were compared with the
biochemical constitution of the stones. The chemical analysis determined that the
stones included 32 calcium-based, 6 cystine and 1 struvite stone. Both HU and
Zeff values were helpful in differentiating calcium-based stones from cystine and
struvite stones and phleboliths. The Zeff values of phleboliths were
significantly higher than those for struvite and cystine stones, whereas it was
difficult to distinguish phleboliths from struvite and cystine stones using the
HU values. Composition analysis using SS-DECT is helpful for distinguishing
urinary stone types and discriminating phleboliths from urinary stones. Zeff
values may be more useful than HU values for differentiating urinary stones from
phleboliths.
PMID- 28420890
TI - Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus
Infection in the Upper Gastrointestinal Tract.
AB - We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age:
51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach,
and/or duodenum diagnosed at a single center, to determine their endoscopic
features and clinical backgrounds. Thirteen patients (92.9%) had hematologic
disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent
allogeneic hematopoietic stem cell transplantation, and 9 of these patients had
graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy
(EGD). All 14 patients had been taking one or more immunosuppressive agents
including cyclosporine (n=10), corticosteroids (n=9), mycophenolic acid (n=6),
tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive
in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric
(n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV
infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric
lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and
verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness
(n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1).
CMV was detected even in the intact duodenal mucosa (n=1). In conclusion,
physicians must recall the relevance of CMV infection when any mucosal
alterations exist in the upper gastrointestinal tract of immunosuppressed
patients.
PMID- 28420892
TI - Adenomyomatosis Concomitant with Primary Gallbladder Carcinoma.
AB - Some clinicians have proposed a relationship between gallbladder (GB) cancer and
adenomyomatosis (ADM) of the gallbladder, although the latter condition is not
considered to have malignant potential. We retrospectively reviewed the surgical
pathology database of patients who underwent resection for ADM of the gallbladder
at our institution from March 2005 to May 2015. In total, 624 patients underwent
surgical resection of the gallbladder with Rokitansky-Aschoff sinuses. Of these
cases, 93 were pathologically diagnosed with ADM of the gallbladder, with 44
(47.3%) classified macroscopically as fundal-type ADM, 26 (28.0%) as segmental
type, and 23 (24.7%) as diffuse-type ADM. In 3 of the 93 (3.2%) resected
specimens, early-stage GB carcinoma was detected, although preoperative imaging
did not suggest a malignant neoplasm of the gallbladder in any of these patients.
GB cancer subsequently developed in the mucosa of the fundal compartment distal
to the annular stricture of the segmental-type ADM in 2 of these patients and
against the background of the fundal-type ADM in 1 patient. This study revealed
the difficulty of early diagnosis of primary GB cancer in the setting of
concurrent ADM, and clinicians should be aware of this frequent coexistence.
PMID- 28420891
TI - Diagnostic Value of Dual-time-point F-18 FDG PET/CT and Chest CT for the
Prediction of Thymic Epithelial Neoplasms.
AB - We retrospectively assessed the dual-time-point (DTP) F-18 FDG PET/CT findings of
thymic epithelial neoplasms (TENs) and investigated the diagnostic capacity of
PET/CT compared to that of CT for predicting carcinoma. We calculated the ratio
of the standardized uptake value of the tumor and that of the aortic arch (T/M
ratio) for both the 90-min early scan and the 2-h delayed scan in 56 TEN
patients. We used a multivariate logistic regression (MLR) analysis to estimate
the CT features of carcinoma. We compared the diagnostic capacities of PET/CT and
chest CT using receiver operating characteristic (ROC) analyses. The ROC curve
revealed that the appropriate cut-off T/M ratio value for the highest accuracy
was 2.39 with 75.0% accuracy. The area under the curve (AUC) was 0.855. The
statistical analyses for DTP scans of 35 TEN patients demonstrated 74.3% accuracy
and 0.838 AUC for the early scan versus 82.9% and 0.825 for the delayed scan. The
MLR analysis indicated that mediastinal fat infiltration was a predictor of
carcinoma. The ROC curve obtained for the model yielded an AUC of 0.853. Delayed
scanning could improve the diagnostic capacity for carcinoma. The T/M ratio and
mediastinal fat infiltration are predictive of carcinoma with moderate diagnostic
accuracy.
PMID- 28420893
TI - Scoliosis in Patients with Severe Cerebral Palsy: Three Different Courses in
Adolescents.
AB - Patients with cerebral palsy (CP) frequently present with scoliosis; however, the
pattern of curve progression is difficult to predict. We aimed to clarify the
natural course of the progression of scoliosis and to identify scoliosis
predictors. This was a retrospective, single-center, observational study. Total
of 92 CP patients from Asahikawasou Ryouiku Iryou Center in Okayama, Japan were
retrospectively analyzed. Cobb angle, presence of hip dislocation and pelvic
obliquity, and Gross Motor Function Classification System (GMFCS) were
investigated. Severe CP was defined as GMFCS level IV or V. The mean observation
period was 10.7 years. Thirtyfour severe CP patients presented with scoliosis and
were divided into 3 groups based on their clinical courses: severe, moderate and
mild. The mean Cobb angles at the final follow-up were 129 degrees , 53 degrees ,
and 13 degrees in the severe, moderate, and mild groups, respectively. The
average progressions from 18 to 25 years were 2.7 degrees /year, 0.7 degrees
/year, and 0.1 degrees /year in the severe, moderate, and mild curve groups,
respectively. We observed the natural course of scoliosis and identified 3
courses based on the Cobb angle at 15 and 18 years of age. This method of
classification may help clinicians predict the patients' disease progression.
PMID- 28420894
TI - Outcome of Radiation Monotherapy for High-risk Patients with Stage I Esophageal
Cancer.
AB - Currently, chemoradiation is the most widely used nonsurgical treatment for
esophageal cancer. However, some patients, particularly the very elderly or those
with severe vital organ dysfunction, face difficulty with the chemotherapy
component. We therefore examined the outcome of radiation therapy (RT) alone for
patients with esophageal cancer at our facility. Between January 2005 and
December 2014, 84 patients underwent RT at our hospital, and 78 of these patients
received concomitant chemotherapy. The remaining 6 patients underwent RT alone;
these patients were considered to be high-risk and to have no lymph node
metastasis (stage I). Five of them received irradiation up to a curative dose: 4
showed a complete response (CR) and 1 showed a partial response (PR). Of the
patients exhibiting CR, 3 are currently living recurrence-free, whereas 1 patient
underwent endoscopic submucosal dissection (ESD) as salvage therapy for local
recurrence, with no subsequent recurrence. High-risk stage I esophageal cancer
patients can be treated radically with RT alone under certain conditions. In the
future, to broaden the indications for RT monotherapy to include some degree of
advanced cancers, a novel concurrent therapy should be identified.
PMID- 28420895
TI - The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and
Its Implication in Human Prostate Cancer Cell Growth Inhibition.
AB - The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key
molecule that promotes cancer progression. We previously developed an adenoviral
vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene
therapy. The therapeutic effects are based on suppressing the growth of cancer
cells, but, the underlying molecular mechanism has not been fully clarified. To
elucidate this mechanism, we investigated the effects of Ad-REIC on the
expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed
that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC
also suppressed the cell growth of LNCaP cells. Since other researchers have
demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c
Myc protein positively regulate the expression of CD147, we investigated the
correlation between the CD147 level and the activation of MAPK and c-Myc
expression. Unexpectedly, no positive correlation was observed between CD147 and
its possible regulators, suggesting that another signaling pathway was involved
in the downregulation of CD147. This is the first study to show the
downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the
therapeutic effects of Ad-REIC may be due to the downregulation of the cancer
progression factor, CD147.
PMID- 28420896
TI - Toe Pinch Force in Male Type 2 Diabetes Mellitus Patients.
AB - We compared the toe pinch force in men with and without type 2 diabetes mellitus
(T2DM). Sixty-eight male T2DM patients and 35 apparently healthy men matched for
age, sex, and body mass index (BMI) were enrolled in this cross-sectional study.
We compared the toe pinch force between the subjects with and without T2DM, and
we evaluated the effect of diabetic polyneuropathy on toe pinch force in the
patients. The toe pinch force of the T2DM patients was significantly lower than
that of the subjects without diabetes (3.12+/-1.22 kg vs. 4.40+/-1.19 kg,
p<0.001). Multiple regression analysis showed that T2DM was a determinant of
reduced toe pinch force. In addition, the toe pinch force of patients with
diabetic polyneuropathy was significantly lower than that of patients without
diabetic polyneuropathy (2.31+/-0.93 kg vs. 3.70+/-1.07 kg, p<0.001). Multiple
regression analysis showed that diabetic polyneuropathy was a determinant of the
toe pinch force in men with T2DM, even after adjusting for age, BMI, HbA1c, and
duration of diabetes. Reduced toe pinch force is a fundamental feature of motor
dysfunction in men with T2DM, and diabetic polyneuropathy might be associated
with toe pinch force in these patients.
PMID- 28420897
TI - In Vivo Analysis of Three-Dimensional Dynamic Scapular Dyskinesis in Scapular or
Clavicular Fractures.
AB - The three-dimensional (3D) kinematics of the scapula were analyzed in vivo in 10
patients with scapular and 10 patients with clavicular fracture. Both the injured
shoulder and normal contralateral shoulder were evaluated by computed tomography
in the neutral and fully elevated positions. 3D rotational and translational
movements of the scapula relative to the thorax during arm elevation were
analyzed. A computer simulation program was used to compare rotational
elevation/depression in the coronal plane, anterior/posterior tilting in the
sagittal plane and protraction/retraction in the axial plane between the normal
and affected sides. Anterior/ posterior translational movement along the X-axis,
upward/downward movement along the Y-axis, and lateral/ medial movement along the
Z-axis in the Euler space during forward elevation were also compared. In
scapular fracture, rotational elevation of the scapula decreased in the coronal
plane and posterior tilting of the scapula increased in the sagittal plane.
Anterior and superior translation were higher in scapular fracture than in the
corresponding normal sides. However, no significant abnormal rotational and
translational kinematic changes were observed during elevation in clavicular
fracture. In vivo 3D computerized motion analysis was useful for evaluating
scapular dyskinesis. Scapular fracture can cause scapular dyskinesis, but not all
clavicular fractures alter scapular motion biomechanics.
PMID- 28420898
TI - Comparison of Kidney Function between Gestational Hypertension and Preeclampsia.
AB - Although gestational hypertension (GH) is thought to be different from
preeclampsia (PE), in Japan GH and PE are usually treated as the same disease
(i.e., pregnancy-induced hypertension). Here we sought to determine whether there
are any differences in fetal growth and maternal kidney function between
pregnancies with PE and those with GH. We retrospectively analyzed 61 GH patients
and 60 PE patients with singleton pregnancies who delivered at Okayama University
Hospital (2008-2015). We compared maternal and perinatal outcomes and maternal
kidney function parameters between the GH and PE pregnancies. The mean values of
maternal age (p=0.01), gestational age at delivery (p<0.0001), placental weight
(p=0.002), birth weight and height (p<0.0001, p=0.0001), and head circumference
standard deviation score (p=0.007) of newborns of the GH group were significantly
higher than those of the PE group. The duration until termination of PE or GH was
not significantly correlated with kidney function. The birth weight percentile
was significantly correlated with kidney function in PE but not GH. However, GH
patients with poor kidney function and small-for-gestational age infants showed
perinatal outcomes similar to those of the PE group. Monitoring kidney function
is thus important for determining the severity of PE and GH.
PMID- 28420899
TI - Three-Dimensional Imaging of Lymphatic System in Lymphedema Legs Using
Interstitial Computed Tomography-lymphography.
AB - As a new trial, we used interstitial computed tomography-lymphography (CT-LG) in
10 patients with lower extremity lymphedema (n=20 limbs) at stage 0, 1, 2, or 3
under the International Society of Lymphology (ISL) classification. In all cases,
CT-LG, lymphoscintigraphy, and indocyanine green fluorescence-lymphography (ICG
LG) were performed. In the examination of the ascending level of depicted
lymphatic vessels, we measured the diameters of lymphatic vessels detected with
CT-LG and conducted an image analysis of dermal backflow of lymph (DB). CT-LG had
better resolution than lymphoscintigraphy and enabled the clear visualization of
lymphatic vessels with a minimum lumen size of 0.7 mm. CT-LG also showed the
three-dimensional architecture of the DB, which originated from deep lymphatic
collectors via branched small lymphatic vessels. Our findings are quite valuable
not only for detailed examinations of lymphedematous sites and for the lymphedema
surgery, but also for investigations of the pathogenesis of lymphedema which has
not yet been established. We observed that lymphoscintigraphy could show the
lymphatic vessels up to the thigh level in all cases, whereas CT-LG enabled the
vessels' visualization up to the leg level at maximum. In conclusion, CT-LG
provided adequate and detailed three-dimensional imaging of the lymphatic system
in lymphedema patients.
PMID- 28420900
TI - Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy.
AB - Newly published clinical practice guidelines recommend intracranial pressure
(ICP) monitoring in critical care for the management of pediatric acute
encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly
studied. We recently performed direct ICP monitoring for two patients. We
observed that although the direct ICP monitoring had clinical benefits with less
body weight gain and no vasopressor use in both cases, this monitoring technique
is still invasive. Future studies should determine the utility of non-invasive
ICP monitoring systems in pAE to further improve the quality of intensive-care
management.
PMID- 28420901
TI - Discrepancy between Non-invasive Prenatal Genetic Testing (NIPT) and Amniotic
Chromosomal Test due to Placental Mosaicism: A Case Report and Literature Review.
AB - We experienced a case of advanced maternal age in which a fetus was found to be
positive for trisomy 18 at re-examination following indeterminate non-invasive
prenatal genetic testing (NIPT), the amniotic fluid chromosomal test revealed a
normal karyotype, and confined placental mosaicism (CPM) was observed in an SNP
microarray analysis of the placenta. The child was born with no defects or
complications. In the present case, the result of the original NIPT at week 15 of
pregnancy was indeterminate and the subsequent re-examination result was
positive; since the definitive normal diagnosis was not reported until the latter
half of week 21, the pregnant patient was subjected to psychological stress for a
long period of time. The problem with NIPT is that most of the fetus-derived cell
free DNA in the maternal blood is not derived directly from the fetus but from
the villus cells of the placenta, leading to indefinite diagnoses; for that
reason, the pregnant patient was subjected to psychological stress for a long
period of time. Of the 18,251 cases undergoing NIPT in the past 2 years in Japan,
51 had indeterminate results; this was the second case in which a subsequent re
examination gave a positive result for trisomy 18.
PMID- 28420903
TI - Contemporary medical education in remote lands.
PMID- 28420902
TI - A Combination Therapy of Partial Nephrectomy and Cryoablation Achieved Good
Cancer Control and Renal Function in Bilateral Synchronous Renal Cell Carcinoma.
AB - We report the case of a 58-year-old Japanese man with bilateral synchronous renal
cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69
mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic
embolization was performed for the left tumor, and 1 month later, a right open
partial nephrectomy was performed. No recurrence was observed during a 16-month
follow-up, and the serum creatinine level has been stable. The prognosis of
bilateral synchronous RCC is better than that of dialysis patients. The novel
approach of combining cryoablation and partial nephrectomy can achieve good
cancer control and renal function in bilateral RCC.
PMID- 28420904
TI - Estimating risk of atherosclerotic cardiovascular diseases in non-atherosclerotic
Pakistani patients: Study conducted at National Institute of Cardiovascular
Diseases, Karachi, Pakistan.
AB - OBJECTIVE: To assess ten-year and lifetime estimated cardiovascular disease risks
in non-atherosclerotic subjects. METHODS: This cross-sectional study was carried
out at the National Institute of Cardiovascular Disease, Karachi, from July 2014
to March 2015, and comprised male and female subjects with multi-ethnic
background, aged 20-79 years and having non-atherosclerotic disease. SPSS 22 was
used for data analysis. RESULTS: Of the 437 participants, 174(39.8%) were men and
263(60.2%) were women. The overall mean age was 42.65+/-11.45 years. The mean age
of men was 43.3+/-12.1 years and that of women was 42.2+/-10.8 years. Moreover,
ten-year and lifetime risk assessment rates were higher in men (50[28.2%] and
86[49.4%] respectively) compared to women (28[10.6%] and 84[31.9%],
respectively). CONCLUSIONS: Urdu-speaking Pakistanis were found to be at higher
risk from atherosclerotic cardiovascular disease.
PMID- 28420905
TI - Effects of supervised aerobic training on the levels of anti-Mullerian hormone
and adiposity measures in women with normo-ovulatory and polycystic ovary
syndrome.
AB - OBJECTIVE: To evaluate the change in the levels of anti-Mullerian hormone,
adiponectin, weight loss and fertility parameters in obese women with or without
polycystic ovary syndrome, following 12 weeks of supervised aerobic exercise.
METHODS: This study was conducted from August 2013 to October 2014 among obese
women with or without polycystic ovary syndrome referred to Obstetrics and
Gynecology clinic, Mansoura University Hospital, Faculty of Medicine, Mansoura,
Egypt. Patients were classified into three age-matched groups; group A had
controls, group B had patients with polycystic ovary syndrome and group C had
obese women. Anti-Mullerian hormone, adiponectin, follicle-stimulating hormone,
oestrogen, fasting insulin, fasting glucose, homeostasis model of assessment of
insulin resistance, antral follicle count, hirsutism score, weight, menstrual
cyclicity and ovulatory function were assessed at baseline and following 12 weeks
of supervised aerobic exercise. Statistical analysis was performed using SPSS 17.
RESULTS: Of the 90 patients, there were 30(33.3%) in each group. The mean age was
28.7+/-3.84 years in group A, 27.9+/-4.1 years in group B and 27.6+/-5.7 in group
C. The 30(33.3%) participants who responded to aerobic exercise interventions
showed significant improvements in reproductive function), with lower baseline
anti-Mullerian hormone levels, greater weight loss and higher adiponectin level
compared to the the 30(33.3%) participants who did not respond to the exercise
programme. Weight loss, fertility hormones, follicle-stimulating hormone,
prolactin, oestrogen, antral follicle count, baseline anti-Mullerian hormone, and
adiponectin were significantly correlated to the improvement in reproductive
function (p<0.05 each). The change in anti-Mullerian hormone and adiponectin
levels correlated significantly with physical activity level in both responders
and non-responders (p<0.05). In women with anovulatory syndromes, there were
significant improvements in ovarian process with an ovulation rate of 13(43.3%)
and a restoration of menstrual cycle with a rate of 17(56.7 %) following 12 weeks
of supervised aerobic exercise. CONCLUSIONS: Moderate aerobic training for 12
weeks had a positive significant effect on reproductive functions via modulating
adiposity, the levels of adiponectin, anti-Mullerian hormone and fertility
hormones.
PMID- 28420906
TI - Comparison of ultrasound and ultrasound plus nerve stimulator guidance axillary
plexus block.
AB - OBJECTIVE: To evaluate the characteristics of axillary plexus blockade applied
using ultrasound only and using ultrasound together with nerve stimulator in
patients undergoing planned forearm, wrist or hand surgery. METHODS: This
randomised, prospective, double-blinded, single-centre study was conducted at
Ankara Numune Training and Research Hospital, Ankara, Turkey, from November 2014
to August 2015, and comprised patients undergoing forearm, wrist or hand surgery.
Participants were separated into 2 groups. In Group 1, the nerve roots required
for the surgical site were located one by one and local anaesthetic was applied
separately to each nerve for the block. In Group 2, the vascular nerve bundle was
located under ultrasound guidance and a total block was achieved by administering
all the local anaesthetic within the nerve sheath. In the operating room,
standard monitorisation was applied. Following preparation of the skin, the
axillary region nerve roots and branches and vascular structures were observed by
examination with a high-frequency ultrasound probe. In both groups, a 22-gauge,
5cm block needle was entered to the axillary region with visualisation of the
whole needle on ultrasound and 20ml local anaesthetic of 0.5% bupivacaine was
injected. SPSS 19 was used for data analysis. RESULTS: Of the 60 participants,
there were 30(50%) in each group. The mean age was 39.1+/-15 years in the group 1
which was the ultrasound nerve stimulation group, and 41.5+/-14.3 years in group
2. The duration of the procedure was longer in group I than in group 2 (p<0.05).
Patient satisfaction values during the procedure were higher in group 2(p<0.05).
In the ulnar sensory examination, the values of the patients in group 1were
higher at 10, 15, 20 and 25 minutes (p<0.05). In the median, radial and ulnar
motor examination, the values of the patients in group 1were higher at 15 and 20
minutes (p<0.05). CONCLUSIONS: Brachial plexus blockade via axillary approach
guided by ultrasound offered excellent quality of sensory and motor block
equivalent to that of the nerve stimulator-guided technique.
PMID- 28420907
TI - Effectiveness of health education programme: Level of knowledge about prevention
of cervical cancer among Saudi female healthcare students.
AB - OBJECTIVE: To evaluate the effectiveness of health education programme on the
knowledge of human papilloma virus among female medical students. METHODS: This
quasi-experimental study was conducted in 2014 at the Princess Nourah bint
Abulrahman University, Riyadh, Saudi Arabia, and comprised female medical
students. An intervention programme was implemented in the form of lectures,
videos, posters, etc. on human papillomavirus. SPSS 20 was used for data
analysis. RESULTS: There were 535 participants in the study. There mean age was
20.3+/-1.3 years. After the intervention, there was a significant increase in the
level of knowledge. Of all, 495(92%) students recognised avoidance of sexually
transmitted disease, vaccination and screening as effective preventive measures.
In comparison to pre-intervention results, significantly higher percentage of
students defined risk factors: sexually transmitted disease 392(73.3%) versus
329(61.8%), and human papillomavirus 293(54.8%) versus 151(28.4%). Knowledge
regarding sensitivity, 280(52.3%) after the campaign versus 160(30.1%)before, and
time to perform Pap smear,229(42.8%) versus 113(21.1%),increased significantly
(p<0.05). CONCLUSIONS: Health education programme was effective in improving the
level of knowledge on human papillomavirus.
PMID- 28420908
TI - Assessment of personality type and medical specialty choice among medical
students from Karachi; using Myers-Briggs Type Indicator (MBTI) tool.
AB - OBJECTIVE: To assess personality type of medical students and associate it with
their choice of medical specialty. METHODS: This cross-sectional study was
conducted in February 2014 at one public and one private medical university of
Karachi, and comprised medical students. A self- administered questionnaire based
on Myers-Briggs type indicator was used to collect data which was analysed using
SPSS 20. RESULTS: Of the 400 participants, there were 200(50%) each from public
and private universities. Of all, 201(50.3%) students were found to be
extroverted and 199(49.8%) were introverted personality types. Clinical fields
were the main preference of students after their medical degree as selected by
317(79.2%) students; of the, Extroverted-Sensing-Feeling-Perceptive was the most
common type identified in39(7.2%) students. Extroverted-Sensing-Feeling
Perceptive 11(2.8%), Extroverted-Sensing-Thinking-Judging 12(3%), Extroverted
Sensing-Feeling-Judging 5(1.3%), Introverted-Sensing-Feeling-Judging 6(1.5%),
Introverted-Sensing-Thinking-Perceptive 7(1.8%) had preference for surgery,
medicine, gynaecology, paediatrics and cardiology, respectively. CONCLUSIONS:
Personality had significant impact on specialty and career choice.
PMID- 28420909
TI - Lidocaine and tenoxicam effectiveness for pain relief during Pipelle: Non
randomised double-blind placebo-controlled trial.
AB - OBJECTIVE: To compare the effectiveness of intrauterine lidocaine infusion with
lidocaine and intravenous tenoxicam for decreasing the pain levels associated
with endometrial biopsy. METHODS: This double-blind, placebo-controlled trial was
conducted at Fatih Sultan Mehmet Training and Research Hospital, Istanbul,
Turkey, from May to November 2015, and comprised patients undergoing endometrial
biopsy with Pipelle. Intrauterine lidocaine infusion, paracervical block with
lidocaine, intravenous tenoxicam or 4ml intravenous normal saline administered
prior to biopsy. The main outcome measure was pain intensity immediately
afterwards and 30minutes after biopsy, determined by a visual analogue scale
score. Number Cruncher Statistical System 2007 was used for statistical analyses.
RESULTS: Of the 232 participants, intrauterine lidocaine infusion group had
59(25.4%) patients, 57(24.6%) were controls while paracervical block group and
intravenous tenoxicam group each had 58(25%) patients. Both visual analogue scale
0 and 30 scores of the control group were significantly higher than the other
three groups (p<0.05). Also, the scores of intravenous tenoxicam group were
significantly higher than both intrauterine lidocaine infusion and paracervical
block with lidocaine groups (p<0.05 each). CONCLUSIONS: Intravenous tenoxicam had
a significantly lower effect than intrauterine lidocaine infusion and
paracervical block with lidocaine during the early period after the procedure.
PMID- 28420910
TI - Awareness and attitudes towards organ donation among medical students at King
Abdulaziz University, Jeddah, Saudi Arabia.
AB - OBJECTIVE: To assess awareness and attitude of medical students about organ
donation. METHODS: This cross-sectional study was conducted in 2014 at King
Abdulaziz University, Jeddah, Saudi Arabia, and comprised medical students. The
participants were asked about their religious and other beliefs towards organ
donation, their reasons for not donating organs, and their personal opinions
about organ donation through a questionnaire. SPSS 21 was used for data analysis.
RESULTS: Of the 481 participants, 250(52%) were females, and 231(48%) were males.
The overall mean age was 21.36+/-1.63 years. Besides, 437(90.9%) students knew
what organ donation means, 433(90%) supported organ donation, and 90(18.7%) knew
someone who had donated an organ. Moreover, 245(50.9%) participants were willing
to donate their organ to their family alone, 198(41.2%) were willing to donate to
any deserving patient while 439(91.3%) rejected that religion precluded organ
donation, and 354(73.6%) did not know about the grafting of organs from a man to
a woman and vice versa. CONCLUSIONS: Awareness and attitude towards organ
donation were not up to the mark among the participants.
PMID- 28420911
TI - Comparison of foeto-maternal outcome in pregnant women with hepatitis E - A
review of 12 years.
AB - OBJECTIVE: To compare adverse maternal and foetal outcome in pregnant women with
hepatitis E immunoglobulin M reactive versus non-reactive. METHODS: This
retrospective study was conducted at the Aga Khan University Hospital, Karachi,
and comprised records of pregnant patients at any gestational age with clinical
and biochemical evidence of hepatitis E from January 2002 and December 2014. .
Maternal and perinatal outcome of the subjects were analysed. SPSS 20 was used
for data analysis. RESULTS: Out of the 200 subjects, 168(84 %) were hepatitis E
immunoglobulin M reactive and 32(16%) were non-reactive. The overall mean age was
26.7+/-4.5 years. Also, 12(7%) patients in the immunoglobulin M reactive group
were admitted to intensive care unit compared to no one from the non-reactive
group. Similarly fulminant hepatic failure was seen in 12(7.1%) patients in the
immunoglobulin M reactive group compared to no one in the other group. Post
partum haemorrhage was more frequent in the immunoglobulin M reactive group
compared to the non-reactive group. There were 5(3%) maternal deaths in the
reactive group compared to no death in the other group. Moreover, 34(20.2%)
neonates of the immunoglobulin M reactive group needed neonatal intensive care
unit admission compared to none in the non-reactive group. There were 4(2.4%)
neonatal deaths in the reactive group. CONCLUSIONS: Participants in the
immunoglobulin M reactive group had a higher percentage of adverse foeto-maternal
outcomes compared to the non-reactive group.
PMID- 28420912
TI - Effectiveness of plain X-ray in detection of fish and chicken bone foreign body
in upper aerodigestive tract.
AB - OBJECTIVE: To assess the use of plain film radiology in the detection of fish and
chicken bones in the upper aerodigestive tract. METHODS: This retrospective chart
review was conducted at the Aga Khan University Hospital, Karachi, and comprised
medical charts of patients who had undergone oesophagoscopy for removal of fish
and chicken bone from 1990 to 2015.SPSS 19 was used for data analysis. RESULTS:
Of the 24 patients, foreign body was detected on X-ray in 7(29.2%) and through
fibre optic laryngoscopy in 13(54.2%).All the patients underwent surgical
intervention for removal of the foreign body. Also, 19(79.2%) patients underwent
direct laryngoscopy and 5(16.7%) required oesophagoscopy. The sensitivity with X
ray was 15% and specificity was zero. The sensitivity of fibre optic laryngoscopy
in comparison to intra-operative findings was 65% and the specificity was 100%.
CONCLUSIONS: X-ray was not found to be an ideal modality to diagnose fish or
chicken bone impaction in the upper aerodigestive tract.
PMID- 28420913
TI - Increasing usage of rapid diagnostics for Dengue virus detection in Pakistan.
AB - OBJECTIVE: To evaluate the trends in usage of dengue virus diagnostics in
Pakistan. METHODS: This retrospective study was conducted at the Aga Khan
University Hospital, Karachi, and comprised data for specimens tested for dengue
virus from January 2012 to December 2015. Test for dengue virus ribonucleic acid
by reverse transcription polymerase chain reaction, dengue virus antigen by
immunochromatic assay and for human immunoglobulin M against dengue virus by
enzyme-linked immunosorbent assay were reviewed. SPSS 17 was used for data
analysis. RESULTS: Overall, 33,577 specimens tested for dengue virus. Of them,
11,995 (35.7%) were positive. among them, 1,039(8.66%) were reported in 2012;
5,791(48.28%) in 2013; 1,027(8.56%) in 2014; and 4,138(34.49%) in 2015. In 2012,
966(93%) of the positive samples were diagnosed by immunoglobulin M-based method
and 73(7%) by non-structural protein-1 antigen. In 2013, 4,401(76%) samples were
tested positive by immunoglobulin M, 1,332(23%) by antigen and 58(1%) by
polymerase chain reaction. The trend continued in 2014, but in 2015, 2,111(51%)
of all dengue positive tests were determined by antigen testing, 1,969(47.6%) by
immunoglobulin M and 58(1.4%) by polymerase chain reaction. CONCLUSIONS: There
was a shift in usage of direct virus identification for rapid diagnosis of dengue
virus compared with host immunoglobulin M testing.
PMID- 28420914
TI - Simulation training using cadaver sheep chest in pleuroscopy - A step towards
skills enhancement.
AB - OBJECTIVE: For assessing the use of if simulation training on animal cadavers as
a useful tool for training in pleuroscopy. METHODS: The email-based cross
sectional study was conducted in December 2014 at Shaikh Zayed Hospital, Federal
Postgraduate Medical Institute, Lahore, Pakistan, and comprised respiratory
physicians and trainees after their participation in a two-day hands-on training
course on pleuroscopy and pleural medical procedures. The responses were analysed
and the responses of physicians and trainees were compared. RESULTS: Of the 44
individuals who attended the course and were contacted through emails, 38(86.4%)
responded, including 20(52.6%) physicians and 18(47.3%) trainees. All the
38(100%) subjects uniformly accepted the utility of simulation training in
enhancing education, improving skill, and improving confidence by repeated
practice, and felt that the inclusion of animal models for learning fundamental
pleuroscopic procedures can help a lot in teaching. CONCLUSIONS: Animal cadavers
can be used as an effective teaching tool for pleuroscopy training.
PMID- 28420915
TI - Paternal malparenting and offspring personality disorders: Mediating effect of
early maladaptive schemas.
AB - OBJECTIVE: To examine the mediating role of maladaptive schemas between
permissive/authoritarian parenting by fathers and personality disorders,
including histrionic, antisocial, narcissistic and depressive attitudes among
adults. METHODS: This cross-sectional study was conducted at the University of
Sargodha, Sargodha, Pakistan, and comprised university students. Data was
collected by administering the parental authority questionnaire, the young schema
questionnaire and the personality diagnostic questionnaire. SPSS 23 was used for
data analysis. The study was completed in one year. It was started from June 2014
and ended in June 2015. RESULTS: Of the 200 participants who were handed the
questionnaires, 100(50%) returned it fully filled up. Of them, 87(87%) were women
and 13(13%) were men. All scales had greater than 0.70 alpha reliability
coefficients. The values of skewness for all scales ranged from 0.10 to
0.86.Permissive parenting style had positive correlation with histrionic
(p<0.05), narcissistic (p<0.05) and antisocial personality disorders (p<0.01).
Authoritarian parenting had positive correlation with early maladaptive schemas
(p<0.01) and depressive personality disorder (p<0.05). CONCLUSIONS: Both
permissive and authoritarian parenting styles led to personality disorders among
offspring in the adult phase of their lives.
PMID- 28420916
TI - The effect of bariatric anaesthesia on postoperative pulmonary functions.
AB - OBJECTIVE: To evaluate respiratory function in the post-operative early period of
patients undergoing bariatric surgery using the sleeve gastrectomy technique.
METHODS: This prospective, observational study was conducted at Bulent Ecevit
University Health Application and Research Centre, Zonguldak, Turkey from June to
December 2014, and comprised patients with planned bariatric sleeve gastrectomy
under general anaesthesia. Participants were visited 12-24 hours before the
operation to record accompanying diseases and demographic data. Before the
operations, respiratory function test, maximum expiratory pressure, maximum
inspiratory pressure and arterial blood gas assessment tests were done and
recorded as T0. After one hour of the operation, Aldrete scores >9 and the above
mentioned tests were repeated and recorded as T1. SPSS 18 and MedCalc 12.2.1.0
were used for statistical analysis. RESULTS: Of the 76 participants, 60(78%) were
women and 16(21%) were men. The overall median age was 39 years (inter-quartile
range: 32-47 years). The mean and median values for forced expiratory volume in 1
second, forced vital capacity, maximum inspiratory pressure, maximum expiratory
pressure and the ratio between partial pressure of oxygen in arterial blood and
fraction of inspired oxygen at T0 were 101+/-17, 102+/-17, 66 (interquartile
range: 59-74), 114 (interquartile range: 100-138) and 379+/-49, respectively,
compared with 78+/-18, 76+/-18, 53 (interquartile range: 48-59), 85
(interquartile range: 73-95) and 331+/-49at T1 (p<0.001 each). Also, 38(50%)
participants were given sugammadex and 38(50%) were given neostigmine. At the end
of the test, sugammadex (odds ratio: 5.80; 95% confidence interval: 1.26-26.69;
p=0.024) and pre-operative ratio between partial pressure of oxygen in arterial
blood and fraction of inspired oxygen (odds ratio: 1.04, 95% confidence interval:
1.02-1.06; p<0.0001) were found to correlate significantly. CONCLUSIONS:
Impairment of respiratory function was found during the early post-operative
period.
PMID- 28420917
TI - Coping strategies, mental health and HIV status: Predictors of suicidal behaviour
among PWIDs.
AB - OBJECTIVE: To understand suicidal behaviour among people who inject drugs.
METHODS: This correlational, cross-sectional study was conducted in two Pakistani
cities of Gujrat and Jhelum from October 2015 to March 2016, and comprised male
injecting-drug users aged18-60 years. Multistage systematic random sampling
method was used. Urdu-translated versions of the brief cope inventory, mental
health status scale and suicidal behaviour questionnaire (revised) were
administered. SPSS 16 was used for data analysis. RESULTS: Of the 200
participants, 83(41.5%) were aged 26-32 years. The prevalence of human
immunodeficiency virus was in 94(47%) cases. Suicidal behaviour was positively
associated with psychological distress and human immunodeficiency virus status
(p<0.05), whereas it was negatively associated with mental health, psychological
well-being and coping strategies (p<0.05). Regression analysis showed mental
health index and psychological well-being were negative predictors, whereas
psychological distress and human immunodeficiency virus status were positive
predictors of suicidal behaviour among the participants (p<0.05). CONCLUSIONS:
The level of stress led people who inject drugs towards suicidal behaviour.
However, the level of stress varied according to the severity of human
immunodeficiency virus and poor mental health.
PMID- 28420918
TI - The role of psychological eating styles in obesity among Turkish adolescents: A
cross-sectional study.
AB - OBJECTIVE: To determine the relationship between eating behaviours and adiposity
indicators including body mass index, waist-hip ratio and waist-height ratio in
adolescents. METHODS: This descriptive, cross-sectional study was conducted at
Kirklareli University Health College, Kirklareli, Turkey, from April to June
2014, and comprised students of the 2013-14 academic year. Height and weight were
measured and students' body mass indexes were calculated. Waist and hip
circumferences were measured. Eating behaviours were evaluated using the three
factor eating questionnaire. SPSS 15 was used for data analysis. RESULTS: Of
the520, 353(67.9%) were female and 167(32.1%) were male. Cognitive restraint and
emotional eating scores of females were significantly higher than those of males
(p<0.05). Cognitive restraint scores of participants who were thin according to
the body mass index were significantly lower than participants who were at normal
weight and who were overweight (p<0.05). Body mass index was significantly and
positively correlated to cognitive restraint and emotional eating subscales,
whereas there was a significant negative correlation between emotional eating and
waist-height ratio (p<0.05 each). Cognitive restraint regarding food intake and
tendency to emotional eating increased the risk of obesity (p<0.05). CONCLUSIONS:
Being inclined to emotional eating and limiting food intake cognitively increased
the risk of obesity.
PMID- 28420919
TI - Association of arginine vasopressin receptor 1a gene polymorphisms with
hepatorenal syndrome.
AB - OBJECTIVE: To assess the association of arginine vasopressin receptor 1a gene
single nucleotide polymorphisms with type I hepatorenal syndrome. METHODS: The
case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou,
China, from January 2012 to June 2014, and comprised patients with type I
hepatorenal syndrome and individuals with cirrhosis who acted as the control
group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide
polymorphisms were analysed by high-resolution melting methods. Statistical
analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%)
were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age
was 42.21+/-11.30years in the hepatorenal syndrome group and 43.69+/-12.60in the
control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity
levels were 154.76+/-51.58, 49.30+/-24.67 and 33.42+/-3.69 in the hepatorenal
syndrome group compared to 181.26+/-64.46, 41.78+/-17.52 and32.98+/-4.81among
controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were
found in the distributions of arginine vasopressin receptor 1a gene rs113481894
locus T allele between type I hepatorenal syndrome patients and the control group
(odds ratio= 2.230; p= 0.040). CONCLUSIONS: T allele located at arginine
vasopressin receptor 1a receptor promoter rs113481894 locus may be associated
with the pathogenesis of type I hepatorenal syndrome.
PMID- 28420920
TI - The many guises of primary hyperparathyroidism: An unchanged scenario.
AB - OBJECTIVE: To study the causes, characteristics and outcome of treatment of
patients with primary hyperparathyroidism. METHODS: This retrospective cohort
analysis was conducted at the Jinnah Postgraduate Medical Centre, Karachi, and
comprised data of patients with primary hyperparathyroidism between 2004 and
2014. .SPSS 17 was used for data analysis. RESULTS: Of the 25 patients,1(4%)was
male and 24(96%) were female. The overall mean age was 41.72+/-15.9 years, with a
mean duration of symptoms of 4.1+/-3.3 years. The mean pre-operative parathyroid
hormone level was 879.48+/-793.51 pg/ml. Skeletal manifestations were reported in
17(68%) patients, whereas 4(16%) patients had renal stone disease. Besides,
2(8.0%) patients presented with severe abdominal pain, 1(4%) had asymptomatic
hypercalcaemia and 1(4%) patient presented with headache and was diagnosed as
parathyroid adenoma in the context of multiple endocrine neoplasia type 2A. All
patients underwent parathyroidectomy. A solitary adenoma was reported in 23(92%)
patients, carcinoma in 1(4%) and an adenoma with hyperplasia of other glands in
1(4%) patient. CONCLUSIONS: A high index of suspicion is required for early
diagnosis of primary hyperparathyroidism.
PMID- 28420921
TI - Potential of ascorbic acid as antioxidant on chemotherapeutic agent induced
change in morphology of testes.
AB - OBJECTIVE: To demonstrate the morphological changes in number of seminiferous
tubules that are produced by anthracycline doxorubicin on the testes of mice.
METHODS: This experimental study was conducted at Dow University of Health
Sciences, Karachi, from March to August 2012, and comprised male mice aged up to
five weeks. The mice were separated into 3 equal groups: A, B and C. Each animal
was treated with normal saline 1ml intraperitoneal in group A, doxorubicin alone
in group B and doxorubicin + vitamin C in group C. At the end of the study,
animals were sacrificed and the testes were kept in Bouin's fluid and tissue
processing and staining were done. SPSS 16 was used for data analysis. RESULTS:
Of the 30 mice, there were 10(33.3%) in each group. The overall mean age was 5+/
1 weeks. The mean number of tubules was 20.28+/-3.29 in group A, 9.39+/-3.01 in
group B and 18.56+/-2.82 in group C. The mean diameter of seminiferous tubules of
testes was 218.26 +/- 7.45um in group A, 123.96+/-11.84 in group B and 180.86+/
12.13 in group C (p<0.001). Co-administration of vitamin C with doxorubicin
significantly reduced (p<0.001) the seminiferous epithelial damage compared to
doxorubicin group. CONCLUSIONS: The antioxidant vitamin C had a significant role
in ameliorating the damage of testes induced by doxorubicin.
PMID- 28420922
TI - Relationship of anthropometric measures with bone mineral density in
postmenopausal non-osteoporotic, osteopenic and osteoporotic women.
AB - Background and objectives: Body mass index (BMI) has been shown to be a more
important predictor of bone mineral density (BMD). The objective of this study
was to investigate the relationship of anthropometric measures including body
mass index with bone mineral density in postmenopausal non-osteoporotic,
osteopenic and osteoporotic women. METHODS: In this cross sectional study
postmenopausal females between 50-70 years of age were recruited and divided into
three groups: non-osteoporotic (n=52), osteopenic (n=69) and osteoporotic females
(n=47). Anthropometric measures and bone mineral density were assessed. ANOVA was
applied to compare groups while Post hoc Tuckey's test was used for multiple
comparisons between the groups. Spearman's rho correlation was used to establish
correlations. RESULTS: Body mass index (p = 0.034) and hip circumference (p =
0.013) were significantly higher in osteopenic as compared to osteoporotic
females and waist to hip ratio was significantly higher (p = 0.005) in
osteoporotic as compared to non-osteoporotic females. Significant positive
correlation of body mass index was found with T-score (p = 0.022) and ultrasound
bone profile index (p< 0.001) in postmenopausal females. CONCLUSIONS: High body
mass index is associated with high bone mineral density and reduced fracture risk
in postmenopausal females. Increasing age and high waist to hip ratio can also
lead to reduced bone mineral density in postmenopausal females.
PMID- 28420923
TI - Effect of body mass index on early outcomes of coronary artery bypass grafting.
AB - OBJECTIVE: To assess the impact of body mass index on early outcomes of coronary
artery bypass grafting in terms of morbidity and mortality. METHODS: This
retrospective comparative study was conducted at Chaudhry Pervaiz Elahi Institute
of Cardiology, Multan, Pakistan, and comprised data of patients who underwent
isolated coronary artery bypass grafting from December 2007 to December 2015.
Analysis of variance and chi-square test were used for analysis of groups formed
on the basis of body mass index. SPSS 20 was used for data analysis. RESULTS: Of
the 2,366 patients, 830(35.1%) had normal body mass index, 1,024(43.3%) were
overweight, 402(16.9%)were obese and 110(4.6%) were morbidly obese. The overall
mean age was 55.82+/-9.58 years. The mean age of morbidly obese patients was
significantly lower (p=0.02). Additive euro score was high in patients with
normal body mass index (p=0.006). Post-op creatine kinase muscle and brain MB
levels and incidence of peri-operative myocardial infarction was significantly
high in obese and morbidly obese groups (p=0.002 and p=0.01, respectively).
Hospital stay time was significantly longer in obese and morbidly obese patients
(p=0.01). The incidence of post-operative complications was the same in all
groups (p>0.05). Operative mortality was also the same between the groups
(p=0.58). CONCLUSIONS: Higher body mass index was associated with increased risk
of short-term morbidity in terms of myocardial infarction after surgery and
increased length of hospital stay. Our study did not support the concept of
obesity paradox.
PMID- 28420924
TI - Physicians' and nurses' medical errors associated with communication failures.
AB - OBJECTIVE: To determine medical errors associated with communication failures
among physicians and nurses. METHODS: This cross-sectional, descriptive study was
conducted at 20 state hospitals and 14 training and research hospitals affiliated
with the Istanbul City Health Directorate in Turkey, and comprised physicians and
nurses. Data were collected between August 2012 and February 2013. A 16-item
questionnaire was used that included questions regarding socio-demographic
features such as age, gender, educational status, institution, occupation and
working years. Questions also aimed at determining medical errors related to
communication failures. The questionnaire was completed by the participants
during face-to-face interviews. RESULTS: Of the 2,273 participants, 1,654(72.8%)
were nurses and 619(27.2%) were physicians. Besides, 340(54.9%) physicians and
811(49.03%) nurses worked in state hospitals. The mean age of the physicians was
37.76+/-9.20 years (range: 22-62 years), and that of the nurses was 32.61+/-7.38
years (range: 17-62 years). Moreover, 137(22.1%) physicians and 258(15.3%) nurses
had previously experienced medical errors. Also, 74(54%) physicians and
135(52.3%) nurses had experienced medical errors due to some communication error.
The most common medical errors by physicians were incorrect drug administration
45(32.8%), and delivery of drugs to the wrong patient by nurses 103(40.7%). In
addition, 58(42.3%) physicians made medical errors in adult surgical clinic
services while 102(39.5%) nurses made medical errors in adult internal medicine
clinics. CONCLUSIONS: The majority of medical errors originated from
communication failures.
PMID- 28420925
TI - Effect of smoking on hearing loss in refractory's factory male worker with
occupational noise exposure in Iran.
AB - OBJECTIVE: To assess the effect of smoking on hearing loss in factory workers
with occupational noise exposure. METHODS: This cross-sectional study was
conducted at Birjand University of Medical Sciences, Birjand, Iran, from May to
July 2013, and comprised smoking and non-smoking factory male workers. All of
them were exposed to occupational noise level more than 85 decibels for at least
10 years. All participants underwent audiometric testing. SPSS 15 was used for
data analysis.. RESULTS: Of the 150 participants, 55(36.7%) were smokers and
95(63.3%) were non-smokers. The mean age of the participants was 43.26+/-7.81
years while the mean working experience was 15.51+/-3.87 years. Furthermore,
18(32.7%) of the smokers and 8(8.4%) of the non-smokers suffered tinnitus
(p=0.07). The mean noise intensity in the working place of the individuals was
89+/-2.63 A-weighted decibels. At a frequency of 500 Hz, the mean hearing loss
was 4.8+/-5.7 decibels among smokers and 3.3+/-4.6 decibels among non-smokers in
the left ear (p=0.52), whereas it was 4.8+/-5.1 decibels and 3.00+/-4.5 decibels
in the right ear (p=0.15). The difference between the smokers and the non-smokers
was significant in both ears at 1000Hz, 2000Hz, 4000Hz and 8000Hz (p<0.05 each).
CONCLUSIONS: Smoking had an additive role in hearing loss among workers who were
in close contact with excessive noise exposure.
PMID- 28420926
TI - Femto-lasik: The recent innovation in laser assisted refractive surgery.
AB - Femtosecond laser has been introduced in refractive surgery to create a thin
hinged corneal flap without using any blade. The current review was planned to
analyse and compare femtosecond-assisted laser in-situ keratomileusis (LASIK),
the latest refractive procedure, with conventional techniques in refractive
surgery. The analysis showed that femtosecond-assisted LASIK yielded more
predictable corneal flaps, lesser ocular aberrations, better uncorrected visual
acuity, lesser variations in intraocular pressure (IOP) and fewer chances of
developing dry eyes. Transient light sensitivity, diffuse lamellar keratitis,
opaque bubble layer, corneal haze and rainbow glare are some of the demerits of
femtosecond-assisted LASIK, but these can be prevented with certain precautions.
The early visual rehabilitation and preservation of corneal anatomy are added
benefits in the long run. Though it is expensive currently, the competition in
market is expected to cut down the cost soon.
PMID- 28420927
TI - In silico analysis of fragile histidine triad involved in regression of
carcinoma.
AB - Hepatocellular carcinoma (HCCa) is a primary malignancy of the liver. Many
different proteins are involved in HCCa including insulin growth factor (IGF) II
, signal transducers and activators of transcription (STAT) 3, STAT4, mothers
against decapentaplegic homolog 4 (SMAD 4), fragile histidine triad (FHIT) and
selective internal radiation therapy (SIRT) etc. The present study is based on
the bioinformatics analysis of FHIT protein in order to understand the proteomics
aspect and improvement of the diagnosis of the disease based on the protein.
Different information related to protein were gathered from different databases,
including National Centre for Biotechnology Information (NCBI) Gene, Protein and
Online Mendelian Inheritance in Man (OMIM) databases, Uniprot database, String
database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Moreover,
the structure of the protein and evaluation of the quality of the structure were
included from Easy modeler programme. Hence, this analysis not only helped to
gather information related to the protein at one place, but also analysed the
structure and quality of the protein to conclude that the protein has a role in
carcinoma.
PMID- 28420928
TI - Road traffic crash related injured and fatal victims in Karachi from 2007 to
2014: A time-series analysis.
AB - Injuries and deaths due to road traffic crashes (RTC) are major public health
concern. The Road Traffic Injury Research and Prevention Center, collects RTC
data on injuries and fatalities from five emergency departments in Karachi. Data
generating process (DGP) for RTC from 2007 to 2014, for monthly number of fatal
and injured victims were analyzed using autoregressive integrated moving average
and vector auto regression, time series models. Results provide strong evidence
that the DGP for the current levels of the number of fatalities and injured owing
to RTCs are significantly influenced by the own past history of the two series.
The analysis with the impulse-response function also indicated that there is a
slight seasonality pattern in the number of injured and fatalities. The similar
behaviour and association of the two variables suggest that certain conditions
e.g. road conditions, weather, volume of vehicles, and accidents might be
persistent in time in Karachi.
PMID- 28420929
TI - Perception of pathology as a future career choice among medical Students from
Karachi, Pakistan: Experience from a private medical school.
AB - To determine the perception of pathology as a future career choice among medical
students of a private medical school from Karachi, Pakistan. A descriptive cross
sectional study was conducted at the Aga Khan University, Karachi, Pakistan. A
total of 201 students participated in this study. All Students were approached
randomly to participate. A total of 201 students participant survey forms were
evaluated in this study. The overall satisfaction level with pathology was
observed in 61.8% of the students. Majority of the students understood
subspecialties which were a part of clinical medicine. Over half of the students
thought pathology as a specialty should be highlighted in a more integrated
manner (59.2%) with a minority favouring a separate pathology rotation (11.9%).
In conclusion, this study indicates that majority of students have a positive
approach towards the field of pathology and favour incorporating it in an
integrative way into the medical school curriculum.
PMID- 28420930
TI - Enterobius vermicularis in tubo-ovarian abscess: A rare and interesting
incidental finding - A case Report.
AB - Enterobius vermicularis is a common intestinal nematode; however, rare
extraintestinal Enterobius infections have been reported from different parts of
the world. Here, we present a case of tubo-ovarian abscess in an otherwise
healthy young sexually active female with no known comorbids with history of on
and off lower abdominal pain for one year and high grade fever for one month. On
the basis of further workup and radiological evaluation, a preoperative diagnosis
of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was
performed laproscopically in July 2015. Histopathology of the resected tissue
revealed necrosis and in one area Enterobius vermicularis was identified
surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of
severe acute and chronic salpingo-oophoritis with abscess formation, secondary to
Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in
tubo-ovarian abscesses are not much different than usual presentations of pelvic
inflammatory diseases and identification of a parasite in a tubo-ovarian tissue
sample is a rare clinical finding. A high index of suspicion on the part of
histopathologist as well as clinician is important for timely diagnosis and
effective management of such cases.
PMID- 28420931
TI - Paediatrics primary myelofibrosis and acute stroke: A rare presentation.
AB - Idiopathic Myelofibrosis is a rare myeloproliferative disorder. In children, it
becomes even rarer. Herein, we report a case of idiopathic myelofibrosis of a 6
year old male patient who presented with complaints of pallor, petechiae and
bleeding from gums. Bone marrow aspirate showed afragmented haemodiluted smears
with erythroid and myeloid precursors scattered throughout. Trephine biopsy
showed increased background fibrotic activity along with clusters of histiocytes.
A diagnosis of paediatric primary myelofibrosis was made on biopsy. The patient
also developed a stroke that resulted in left-sided hemiparesis. An MRI suggested
an intraparenchymal haemorrhage along with meningeal extramedullary
haematopoiesis.
PMID- 28420932
TI - Sporadic actinomycosis of the hip complicated by Central Nervous System
infection.
AB - Actinomycosis is caused by the Gram positive filamentous Actinomyces bacterial
species that are normal commensals of the oral cavity. Due to their low
virulence, disease is rare in the immune competent patient. Although it may
afflict any system in the body, involvement of the musculoskeletal system is
uncommon. Here in, we describe the case of a 60 year old lady presenting with low
grade fever, left hip pain and drowsiness. She was diagnosed as left hip
actinomycosis on Computed tomogram (CT) guided biopsy and histopathological
analysis of infiltrative lesions identified on Magnetic Resonance Imaging (MRI).
She also had meningitis diagnosed on cerebrospinal fluid analysis which improved
with treatment of actinomycosis. Actinomycosis of the hip is rare, and occurs in
the presence of described predisposing factors. To the best of our knowledge,
this is the first case of sporadic actinomycosis of the hip complicated by
meningitis in an immune competent individual.
PMID- 28420933
TI - Gestational diabetes mellitus: Berlin and beyond.
AB - The Berlin Declaration is a landmark call to action, which encourages policy
makers to take early action to halt the type 2 diabetes epidemic. It emphasizes
the need for prevention, early detection, early control, and early access to the
right interventions. We believe these four pillars of early action in type 2
diabetes are as relevant to gestational diabetes mellitus (GDM) and action in the
latter will impact on the former. Therefore this statement, authored by 21
experts from 14 countries calls for early action in GDM. We highlight the
relative invisibility of GDM, and underscore the significance of GDM prevention
and management in the fight against diabetes. We also provide evidence for the
feasibility in applying each Berlin Declaration pillar to GDM, and highlight the
trans generational benefits this will have in containing the diabetes epidemic.
PMID- 28420934
TI - Preconception management of thyroid disorders.
AB - Thyroid function is closely interlinked with pregnancy. Maternal and foetal
outcomes can be improved if optimal thyroid function is achieved, and maintained
prior to conception. This needs a systematic approach which includes rational
screening, appropriate management, and pragmatic counseling. This review
describes pre-conception management of thyroid disorders, and completes an
earlier article on preconception management of other endocrine diseases.
PMID- 28420935
TI - Prevention of hypoglycaemia, the ASAP (Anticipate, Suspect, Act, Prevent)
strategy.
AB - This article describes a simple framework to prevent hypoglycaemia. Four
strategies of prevention are detailed, which correspond to four levels of
prevention (primordial, primary, secondary and tertiary). This framework, given
the mnemonic ASAP (As Soon As Possible) includes action to Anticipate and Avoid,
and Suspect and Screen hypoglycaemia. It also enjoins us to Act and Assist
persons with hypoglycaemia in a timely manner, while working to Prevent and
Protect them by using safer glucose lowering drugs and insulins.
PMID- 28420936
TI - LINX Reflux Management System - Is it a permanent solution for GERD?
PMID- 28420937
TI - Rise and stalling of public health in Pakistan.
PMID- 28420938
TI - Assessment of the 3-D vision syndrome among the Spectators of Three-Dimensional
(3-d) Movies in Karachi-Pakistan.
PMID- 28420939
TI - Oncolytic viral therapy.
PMID- 28420940
TI - PREVALENCE OF HEPATITIS B SURFACE ANTIGEN AND ANTIBODY IN HEALTHY SUBJECTS AND
PATIENTS WITH LIVER DISEASE.
PMID- 28420941
TI - Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory
Bowel Disease.
AB - Cytokines play an important role in the immunopathogenesis of inflammatory bowel
disease (IBD), including Crohn's disease and ulcerative colitis, where they drive
and regulate multiple aspects of intestinal inflammation. The imbalance between
proinflammatory and anti-inflammatory cytokines that occurs in IBD results in
disease progression and tissue damage and limits the resolution of inflammation.
Targeting cytokines have been novel strategies in the treatment of IBD. Recent
studies show the beneficial effects of anticytokine treatments to IBD patients,
and multiple novel cytokines are found to be involved in the pathogenesis of IBD.
In this review, we will discuss the recent advances of novel biologics in clinics
and clinical trials, and novel proinflammatory and anti-inflammatory cytokines
found in IBD with focusing on IL-12 family and IL-1 family members as well as
their relevance to the potential therapy of IBD.
PMID- 28420942
TI - Temporomandibular Disorders and Headache: A Retrospective Analysis of 1198
Patients.
AB - Aim. Headache is one of the most common diseases associated with
Temporomandibular Disorders (TMDs). The aim of this study was to evaluate,
retrospectively, if headache influences TMD's symptoms. Material and Methods. A
total sample of 1198 consecutive TMD patients was selected. After a neurological
examination, a diagnosis of headache, according to the latest edition of the
International Classification of Headache Disorders, was performed in 625
subjects. Patients were divided into two groups based on presence/absence of
headache: Group with Headache (GwH) and Group without Headache (GwoH).
Descriptive statistics and Chi-square index were performed. Results.
Sociodemographic (gender, marital status, and occupation) and functional factors,
occlusion (occlusal and skeletal classes, dental formula, and occlusal
abnormalities), and familiar pain did not show a statistically significant
correlation in either group. Intensity and frequency of neck pain, arthralgia of
TMJ, and myalgia showed higher correlation values in GwH. Conclusion. This study
is consistent with previous literature in showing a close relationship between
headache and TMD. All data underlines that headache makes pain parameters more
intense and frequent. Therefore, an early and multidisciplinary treatment of TMDs
should be performed in order to avoid the overlay of painful events that could
result in pain chronicity.
PMID- 28420943
TI - Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived
Neurotrophic Factor Expression in the Central Nervous System in Rats with
Neuropathic Pain Induced by CCI in Rats.
AB - Background. Glial cells are implicated in the development of chronic pain and
brain-derived neurotropic factor (BDNF) released from activated microglia
contributes to the nociceptive transmission. Neural mobilization (NM) technique
is a method clinically effective in reducing pain sensitivity. Here we examined
the involvement of glial cells and BDNF expression in the thalamus and midbrain
after NM treatment in rats with chronic constriction injury (CCI). CCI was
induced and rats were subsequently submitted to 10 sessions of NM, every other
day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial
fibrillary acidic protein (GFAP), microglial cell OX-42, and BDNF using
Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of
CCI group showed increases in GFAP, OX-42, and BDNF expression compared with
control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after
NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42,
and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal
gray in midbrain was shown by immunohistochemistry. Conclusions. These findings
may improve the knowledge about the involvement of astrocytes, microglia, and
BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic
pain, affects glial cells and BDNF expression.
PMID- 28420944
TI - New Therapies for Hepatitis C Virus Infection.
AB - Approximately 350 million people worldwide are infected with hepatitis C virus
(HCV), which is associated with morbidity and mortality related to cirrhosis,
hepatocellular carcinoma, or liver failure. Recently, vast improvements have been
made with the development of direct-acting antiviral (DAA) agents, which are all
oral, are better tolerated than interferon-based treatment, and provide a
sustained virologic response in more than 90% of treated patients. This article
reviews the new therapies available for HCV infection, with a focus on patients
who have chronic HCV with and without compensated cirrhosis. As DAA development
continues, more attention will need to be given to special patient populations,
specifically to patients who fail treatment due to emerging resistant strains.
Considerable challenges yet to be overcome are incremental diagnosis of
unidentified patients and linkage to care that is affordable and available to all
patients.
PMID- 28420945
TI - Controversies and Recent Developments of the Low-FODMAP Diet.
AB - The low-fermentable oligo-, di-, and monosaccharide and polyol (FODMAP) diet is a
2-phased intervention, with strict reduction of all slowly absorbed or
indigestible short-chain carbohydrates (ie, FODMAPs) followed by reintroduction
of specific FODMAPs according to tolerance. The efficacy of the elimination phase
of the FODMAP diet is well established, but the success of maintaining this diet
has been shown in only a few observational studies. How the efficacy of the low
FODMAP diet compares with that of other therapies has received limited attention,
but recent studies have shown this diet to be comparable or superior to diets
that address eating style and choice of food as well as to gut hypnotherapy.
There has been no comparison between the low-FODMAP diet and the gluten-free
diet, which moderately reduces FODMAP intake. Mechanistically, dietary FODMAPs
have very limited effects on the consistency of bowel actions but seem to
suppress the release of histamine. Neither symptom pattern nor breath hydrogen
testing for fructose or polyol malabsorption is a useful predictor of efficacy,
but analysis of gut microbiota has potential. As a restrictive diet, the low
FODMAP diet carries risks of nutritional inadequacy and of fostering disordered
eating, which has received little attention. Strict FODMAP restriction induces a
potentially unfavorable gut microbiota, although the impact of this consequence
upon health is unknown. This observation puts additional impetus on the
reintroduction of FODMAPs according to tolerance during the maintenance phase of
the diet. Studies of the low-FODMAP diet in children are few but do suggest
benefit. However, such a strategy should be implemented with care due to the
psychological and nutritional risks of a restrictive diet. Clinical wisdom is
required in utilizing the low-FODMAP diet.
PMID- 28420946
TI - An Overview of Transoral Incisionless Fundoplication and Magnetic Sphincter
Augmentation for GERD.
PMID- 28420947
TI - The Use of Fecal Calprotectin in Inflammatory Bowel Disease.
PMID- 28420948
TI - Nonradiation, Endoscopic Ultrasound-Based Endoscopic Retrograde
Cholangiopancreatography.
PMID- 28420949
TI - Removal of Zinc from Aqueous Solution by Optimized Oil Palm Empty Fruit Bunches
Biochar as Low Cost Adsorbent.
AB - This study aims to produce optimized biochar from oil palm empty fruit bunches
(OPEFB), as a green, low cost adsorbent for uptake of zinc from aqueous solution.
The impact of pyrolysis conditions, namely, highest treatment temperature (HTT),
heating rate (HR), and residence time (RT) on biochar yield and adsorption
capacity towards zinc, was investigated. Mathematical modeling and optimization
of independent variables were performed employing response surface methodology
(RSM). HTT was found to be the most influential variable, followed by residence
time and heating rate. Based on the central composite design (CCD), two quadratic
models were developed to correlate three independent variables to responses. The
optimum production condition for OPEFB biochar was found as follows: HTT of 615
degrees C, HR of 8 degrees C/min, and RT of 128 minutes. The optimum biochar
showed 15.18 mg/g adsorption capacity for zinc and 25.49% of yield which was in
agreement with the predicted values, satisfactory. Results of the
characterization of optimum product illustrated well-developed BET surface area
and porous structure in optimum product which favored its sorptive ability.
PMID- 28420950
TI - Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies.
AB - Metallothioneins (MTs) are proteins that function by metal exchange to regulate
the bioavailability of metals, such as zinc and copper. Copper functions in the
brain to regulate mitochondria, neurotransmitter production, and cell signaling.
Inappropriate copper binding can result in loss of protein function and
Cu(I)/(II) redox cycling can generate reactive oxygen species. Copper accumulates
in the brain with aging and has been shown to bind alpha-synuclein and initiate
its aggregation, the primary aetiological factor in Parkinson's disease (PD), and
other alpha-synucleinopathies. In PD, total tissue copper is decreased, including
neuromelanin-bound copper and there is a reduction in copper transporter CTR-1.
Conversely cerebrospinal fluid (CSF) copper is increased. MT-1/2 expression is
increased in activated astrocytes in alpha-synucleinopathies, yet expression of
the neuronal MT-3 isoform may be reduced. MTs have been implicated in
inflammatory states to perform one-way exchange of copper, releasing free zinc
and recent studies have found copper bound to alpha-synuclein is transferred to
the MT-3 isoform in vitro and MT-3 is found bound to pathological alpha-synuclein
aggregates in the alpha-synucleinopathy, multiple systems atrophy. Moreover, both
MT and alpha-synuclein can be released and taken up by neural cells via specific
receptors and so may interact both intra- and extra-cellularly. Here, we
critically review the role of MTs in copper dyshomeostasis and alpha-synuclein
aggregation, and their potential as biomarkers and therapeutic targets.
PMID- 28420951
TI - Shared Neural Mechanisms for the Prediction of Own and Partner Musical Sequences
after Short-term Piano Duet Training.
AB - Predictive mechanisms in the human brain can be investigated using markers for
prediction violations like the mismatch negativity (MMN). Short-term piano
training increases the MMN for melodic and rhythmic deviations in the training
material. This increase occurs only when the material is actually played, not
when it is only perceived through listening, suggesting that learning predictions
about upcoming musical events are derived from motor involvement. However, music
is often performed in concert with others. In this case, predictions about
upcoming actions from a partner are a crucial part of the performance. In the
present experiment, we use magnetoencephalography (MEG) to measure MMNs to
deviations in one's own and a partner's musical material after both engaged in
musical duet training. Event-related field (ERF) results revealed that the MMN
increased significantly for own and partner material suggesting a neural
representation of the partner's part in a duet situation. Source analysis using
beamforming revealed common activations in auditory, inferior frontal, and
parietal areas, similar to previous results for single players, but also a
pronounced contribution from the cerebellum. In addition, activation of the
precuneus and the medial frontal cortex was observed, presumably related to the
need to distinguish between own and partner material.
PMID- 28420952
TI - Motion-Induced Position Shifts Activate Early Visual Cortex.
AB - The ability to correctly determine the position of objects in space is a
fundamental task of the visual system. The perceived position of briefly
presented static objects can be influenced by nearby moving contours, as
demonstrated by various illusions collectively known as motion-induced position
shifts. Here we use a stimulus that produces a particularly strong effect of
motion on perceived position. We test whether several regions-of-interest (ROIs),
at different stages of visual processing, encode the perceived rather than
retinotopically veridical position. Specifically, we collect functional MRI data
while participants experience motion-induced position shifts and use a
multivariate pattern analysis approach to compare the activation patterns evoked
by illusory position shifts with those evoked by matched physical shifts. We find
that the illusory perceived position is represented at the earliest stages of the
visual processing stream, including primary visual cortex. Surprisingly, we found
no evidence of percept-based encoding of position in visual areas beyond area V3.
This result suggests that while it is likely that higher-level visual areas are
involved in position encoding, early visual cortex also plays an important role.
PMID- 28420954
TI - Multiple Kernel Based Region Importance Learning for Neural Classification of
Gait States from EEG Signals.
AB - With the development of Brain Machine Interface (BMI) systems, people with motor
disabilities are able to control external devices to help them restore movement
abilities. Longitudinal validation of these systems is critical not only to
assess long-term performance reliability but also to investigate adaptations in
electrocortical patterns due to learning to use the BMI system. In this paper, we
decode the patterns of user's intended gait states (e.g., stop, walk, turn left,
and turn right) from scalp electroencephalography (EEG) signals and
simultaneously learn the relative importance of different brain areas by using
the multiple kernel learning (MKL) algorithm. The region of importance (ROI) is
identified during training the MKL for classification. The efficacy of the
proposed method is validated by classifying different movement intentions from
two subjects-an able-bodied and a spinal cord injury (SCI) subject. The
preliminary results demonstrate that frontal and fronto-central regions are the
most important regions for the tested subjects performing gait movements, which
is consistent with the brain regions hypothesized to be involved in the control
of lower-limb movements. However, we observed some regional changes comparing the
able-bodied and the SCI subject. Moreover, in the longitudinal experiments, our
findings exhibit the cortical plasticity triggered by the BMI use, as the
classification accuracy and the weights for important regions-in sensor space
generally increased, as the user learned to control the exoskeleton for movement
over multiple sessions.
PMID- 28420953
TI - Using Cochlear Microphonic Potentials to Localize Peripheral Hearing Loss.
AB - The cochlear microphonic (CM) is created primarily by the receptor currents of
outer hair cells (OHCs) and may therefore be useful for identifying cochlear
regions with impaired OHCs. However, the CM measured across the frequency range
with round-window or ear-canal electrodes lacks place-specificity as it is
dominated by cellular sources located most proximal to the recording site (e.g.,
at the cochlear base). To overcome this limitation, we extract the "residual" CM
(rCM), defined as the complex difference between the CM measured with and without
an additional tone (saturating tone, ST). If the ST saturates receptor currents
near the peak of its excitation pattern, then the rCM should reflect the activity
of OHCs in that region. To test this idea, we measured round-window CMs in
chinchillas in response to low-level probe tones presented alone or with an ST
ranging from 1 to 2.6 times the probe frequency. CMs were measured both before
and after inducing a local impairment in cochlear function (a 4-kHz notch-type
acoustic trauma). Following the acoustic trauma, little change was observed in
the probe-alone CM. In contrast, rCMs were reduced in a frequency-specific
manner. When shifts in rCM levels were plotted vs. the ST frequency, they matched
well the frequency range of shifts in neural thresholds. These results suggest
that rCMs originate near the cochlear place tuned to the ST frequency and thus
can be used to assess OHC function in that region. Our interpretation of the data
is supported by predictions of a simple phenomenological model of CM generation
and two-tone interactions. The model indicates that the sensitivity of rCM to
acoustic trauma is governed by changes in cochlear response at the ST tonotopic
place rather than at the probe place. The model also suggests that a combination
of CM and rCM measurements could be used to assess both the site and etiology of
sensory hearing loss in clinical applications.
PMID- 28420955
TI - Hemispheric Differences in White Matter Microstructure between Two Profiles of
Children with High Intelligence Quotient vs. Controls: A Tract-Based Spatial
Statistics Study.
AB - Objectives: The main goal of this study was to investigate and compare the neural
substrate of two children's profiles of high intelligence quotient (HIQ).
Methods: Two groups of HIQ children were included with either a homogeneous (Hom
HIQ: n = 20) or a heterogeneous IQ profile (Het-HIQ: n = 24) as defined by a
significant difference between verbal comprehension index and perceptual
reasoning index. Diffusion tensor imaging was used to assess white matter (WM)
microstructure while tract-based spatial statistics (TBSS) analysis was performed
to detect and localize WM regional differences in fractional anisotropy (FA),
mean diffusivity, axial (AD), and radial diffusivities. Quantitative measurements
were performed on 48 regions and 21 fiber-bundles of WM. Results: Hom-HIQ
children presented higher FA than Het-HIQ children in widespread WM regions
including central structures, and associative intra-hemispheric WM fasciculi. AD
was also greater in numerous WM regions of Total-HIQ, Hom-HIQ, and Het-HIQ groups
when compared to the Control group. Hom-HIQ and Het-HIQ groups also differed by
their hemispheric lateralization in AD differences compared to Controls. Het-HIQ
and Hom-HIQ groups showed a lateralization ratio (left/right) of 1.38 and 0.78,
respectively. Conclusions: These findings suggest that both inter- and intra
hemispheric WM integrity are enhanced in HIQ children and that neural substrate
differs between Hom-HIQ and Het-HIQ. The left hemispheric lateralization of Het
HIQ children is concordant with their higher verbal index while the relative
right hemispheric lateralization of Hom-HIQ children is concordant with their
global brain processing and adaptation capacities as evidenced by their
homogeneous IQ.
PMID- 28420956
TI - Retinal Gene Therapy: Surgical Vector Delivery in the Translation to Clinical
Trials.
AB - An exceptionally high number of monogenic disorders lead to incurable blindness,
making them targets for the development of gene-therapy. In order to successfully
apply therapeutic vector systems in vivo, the heterogeneity of the disease
phenotype needs to be considered. This necessitates tailored approaches such as
subretinal or intravitreal injections with the aim to maximize transduction of
target cell populations, while minimizing off-target effects and surgical
complications. Strategic decisions on parameters of the application are crucial
to obtain the best treatment outcomes and patient safety. While most of the
current retinal gene therapy trials utilize a subretinal approach, a deeper
understanding of the numerous factors and considerations in choosing one delivery
approach over the other for various ocular pathologies could lead to an improved
safety and treatment efficacy. In this review we survey different vector
injection techniques and parameters applied in recent retinal (pre-)clinical
trials. We explore the advantages and shortcomings of each delivery strategy in
the setting of different underlying ocular pathologies and other relevant
factors. We highlight the potential benefits for patient safety and efficacy in
applying those considerations in the decision making process.
PMID- 28420957
TI - Neuropeptide Y-Induced Orexigenic Action Is Attenuated by the Orexin Receptor
Antagonist in Bullfrog Larvae.
AB - In bullfrog larvae at the pre- and pro-metamorphic stages, feeding behavior is
regulated by appetite factors such as orexigenic peptides. In fact, food intake
is enhanced by intracerebroventricular (ICV) administration of neuropeptide Y
(NPY) and orexin A. Using goldfish, our previous study indicated that the
orexigenic action of NPY is mediated by orexin A, suggesting the functional
interaction between the two. However, there is little information about whether
the action of orexin A mediates the orexigenic action of NPY in bullfrog larvae.
Therefore, we examined the effect of the orexin receptor antagonist, SB334867 on
the orexigenic action of NPY in larvae. The stimulatory effect of ICV injection
of NPY at 10 pmol/g body weight (BW) on food intake was abolished by treatment
with SB334867 at 60 pmol/g BW. These results suggest that, in bullfrog larvae,
there is a neuronal relationship between the NPY and orexin systems, and that the
orexigenic action of NPY is mediated by the orexin A-induced orexigenic action.
PMID- 28420958
TI - Electrical Stimulation of Afferent Pathways for the Suppression of Pathological
Tremor.
AB - Pathological tremors are involuntary oscillatory movements which cannot be fully
attenuated using conventional treatments. For this reason, several studies have
investigated the use of neuromuscular electrical stimulation for tremor
suppression. In a recent study, however, we found that electrical stimulation
below the motor threshold also suppressed tremor, indicating involvement of
afferent pathways. In this study, we further explored this possibility by
systematically investigating how tremor suppression by afferent stimulation
depends on the stimulation settings. In this way, we aimed at identifying the
optimal stimulation strategy, as well as to elucidate the underlying
physiological mechanisms of tremor suppression. Stimulation strategies varying
the stimulation intensity and pulse timing were tested in nine tremor patients
using either intramuscular or surface stimulation. Significant tremor suppression
was observed in six patients (tremor suppression > 75% was observed in three
patients) and the average optimal suppression level observed across all subjects
was 52%. The efficiency for each stimulation setting, however, varied
substantially across patients and it was not possible to identify a single set of
stimulation parameters that yielded positive results in all patients. For
example, tremor suppression was achieved both with stimulation delivered in an
out-of-phase pattern with respect to the tremor, and with random timing of the
stimulation. Overall, these results indicate that low-current stimulation of
afferent fibers is a promising approach for tremor suppression, but that further
research is required to identify how the effect can be maximized in the
individual patient.
PMID- 28420959
TI - Transcranial Direct Current Stimulation Does Not Affect Lower Extremity Muscle
Strength Training in Healthy Individuals: A Triple-Blind, Sham-Controlled Study.
AB - The present study investigated the effects of anodal transcranial direct current
stimulation (tDCS) on lower extremity muscle strength training in 24 healthy
participants. In this triple-blind, sham-controlled study, participants were
randomly allocated to the anodal tDCS plus muscle strength training (anodal tDCS)
group or sham tDCS plus muscle strength training (sham tDCS) group. Anodal tDCS
(2 mA) was applied to the primary motor cortex of the lower extremity during
muscle strength training of the knee extensors and flexors. Training was
conducted once every 3 days for 3 weeks (7 sessions). Knee extensor and flexor
peak torques were evaluated before and after the 3 weeks of training. After the 3
week intervention, peak torques of knee extension and flexion changed from 155.9
to 191.1 Nm and from 81.5 to 93.1 Nm in the anodal tDCS group. Peak torques
changed from 164.1 to 194.8 Nm on extension and from 78.0 to 85.6 Nm on flexion
in the sham tDCS group. In both groups, peak torques of knee extension and
flexion significantly increased after the intervention, with no significant
difference between the anodal tDCS and sham tDCS groups. In conclusion, although
the administration of eccentric training increased knee extensor and flexor peak
torques, anodal tDCS did not enhance the effects of lower extremity muscle
strength training in healthy individuals. The present null results have crucial
implications for selecting optimal stimulation parameters for clinical trials.
PMID- 28420960
TI - Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action
Potentials.
AB - Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal
auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit
provides the neural substrate for the MOC reflex, which inhibits cochlear
amplifier gain and is believed to play a role in listening in noise and
protection from acoustic overexposure. The human MOC reflex has been studied
extensively using otoacoustic emissions (OAE) paradigms; however, these
measurements are insensitive to subsequent "downstream" efferent effects on the
neural ensembles that mediate hearing. In this experiment, click- and chirp
evoked auditory nerve compound action potential (CAP) amplitudes were measured
electrocochleographically from the human eardrum without and with MOC reflex
activation elicited by contralateral broadband noise. We hypothesized that the
chirp would be a more optimal stimulus for measuring neural MOC effects because
it synchronizes excitation along the entire length of the basilar membrane and
thus evokes a more robust CAP than a click at low to moderate stimulus levels.
Chirps produced larger CAPs than clicks at all stimulus intensities (50-80 dB
ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low
stimulus levels when quantified both in terms of amplitude reduction and
effective attenuation. Effective attenuation was larger for chirp- and click
evoked CAPs than for click-evoked OAEs measured from the same subjects. Our
results suggest that the chirp is an optimal stimulus for evoking CAPs at low
stimulus intensities and for assessing MOC reflex effects on the auditory nerve.
Further, our work supports previous findings that MOC reflex effects at the level
of the auditory nerve are underestimated by measures of OAE inhibition.
PMID- 28420961
TI - The Role of Astrocytes in Neuroprotection after Brain Stroke: Potential in Cell
Therapy.
AB - Astrocytes are commonly involved in negative responses through their
hyperreactivity and glial scar formation in excitotoxic and/or mechanical
injuries. But, astrocytes are also specialized glial cells of the nervous system
that perform multiple homeostatic functions for the survival and maintenance of
the neurovascular unit. Astrocytes have neuroprotective, angiogenic,
immunomodulatory, neurogenic, and antioxidant properties and modulate synaptic
function. This makes them excellent candidates as a source of neuroprotection and
neurorestoration in tissues affected by ischemia/reperfusion, when some of their
deregulated genes can be controlled. Therefore, this review analyzes pro-survival
responses of astrocytes that would allow their use in cell therapy strategies.
PMID- 28420962
TI - Dysregulation of RNA Binding Protein Aggregation in Neurodegenerative Disorders.
AB - The unique biology of RNA binding proteins is altering our view of the genesis of
protein misfolding diseases. These proteins use aggregation of low complexity
domains (LCDs) as a means to regulate the localization and utilization of RNA by
forming RNA granules, such as stress granules, transport granules and P-bodies.
The reliance on reversible aggregation as a mechanism for biological regulation
renders this family of proteins highly vulnerable to promoting diseases of
protein misfolding. Mutations in RNA binding proteins are associated with many
neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) and
frontotemporal lobar dementia (FTLD). The biology of RNA binding proteins also
extends to microtubule associated protein tau. Tau is normally an axonal protein,
but in stress it translocates to the somatodendritic arbor where it takes on a
new function promoting formation of stress granules. The interaction of tau with
stress granules also promotes tau aggregation, accelerating formation of the tau
pathology that we associate with diseases such as Alzheimer's disease (AD).
PMID- 28420963
TI - RNA-Seq Analysis of Microglia Reveals Time-Dependent Activation of Specific
Genetic Programs following Spinal Cord Injury.
AB - Neurons have inherent competence to regrow following injury, although not
spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation
driven by resident microglia and infiltrating peripheral macrophages. Microglia
are the first reactive glial population after SCI and participate in recruitment
of monocyte-derived macrophages to the lesion site. Both positive and negative
influence of microglia and macrophages on axonal regeneration had been reported
after SCI, raising the issue whether their response depends on time post-lesion
or different lesion severity. We analyzed molecular alterations in microglia at
several time-points after different SCI severities using RNA-sequencing. We
demonstrate that activation of microglia is time-dependent post-injury but is
independent of lesion severity. Early transcriptomic response of microglia after
SCI involves proliferation and neuroprotection, which is then switched to
neuroinflammation at later stages. Moreover, SCI induces an autologous microglial
expression of astrocytic markers with over 6% of microglia expressing glial
fibrillary acidic protein and vimentin from as early as 72 h post-lesion and up
to 6 weeks after injury. We also identified the potential involvement of DNA
damage and in particular tumor suppressor gene breast cancer susceptibility gene
1 (Brca1) in microglia after SCI. Finally, we established that BRCA1 protein is
specifically expressed in non-human primate spinal microglia and is upregulated
after SCI. Our data provide the first transcriptomic analysis of microglia at
multiple stages after different SCI severities. Injury-induced microglia
expression of astrocytic markers at RNA and protein levels demonstrates novel
insights into microglia plasticity. Finally, increased microglia expression of
BRCA1 in rodents and non-human primate model of SCI, suggests the involvement of
oncogenic proteins after CNS lesion.
PMID- 28420964
TI - Identification of the Spinal Expression Profile of Non-coding RNAs Involved in
Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.
AB - Neuropathic pain (NP) is caused by damage to the nervous system, resulting in
aberrant pain, which is associated with gene expression changes in the sensory
pathway. However, the molecular mechanisms are not fully understood. A non-coding
Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a
protein. NcRNAs are involved in many cellular processes, and mutations or
imbalances of the repertoire within the body can cause a variety of diseases.
Although ncRNAs have recently been shown to play a role in NP pathogenesis, the
specific effects of ncRNAs in NP remain largely unknown. In this study,
sequencing analysis was performed to investigated the expression patterns of
ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of
134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs
(circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared
nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain
reaction (PCR) was performed to validate the expression of selected lncRNAs,
miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to
explore the potential ncRNA functions and relationships. Our data showed that the
most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt
signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and
protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA
miRNA-mRNA network of NP was constructed. This is the first study to
comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate
the involvement of different ncRNA expression patterns in the spinal cord of NP
pathogenesis by sequence analysis. This information will enable further research
on the pathogenesis of NP and facilitate the development of novel NP therapeutics
targeting ncRNAs.
PMID- 28420966
TI - Fast and Slow Inhibition in the Visual Thalamus Is Influenced by Allocating GABAA
Receptors with Different gamma Subunits.
AB - Cell-type specific differences in the kinetics of inhibitory postsynaptic
conductance changes (IPSCs) are believed to impact upon network dynamics
throughout the brain. Much attention has focused on how GABAA receptor (GABAAR)
alpha and beta subunit diversity will influence IPSC kinetics, but less is known
about the influence of the gamma subunit. We have examined whether GABAAR gamma
subunit heterogeneity influences IPSC properties in the thalamus. The gamma2
subunit gene was deleted from GABAARs selectively in the dorsal lateral
geniculate nucleus (dLGN). The removal of the gamma2 subunit from the dLGN
reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and
produced an absence of IPSCs in a subset of relay neurons. The remaining slower
IPSCs were both insensitive to diazepam and zinc indicating the absence of the
gamma2 subunit. Because these slower IPSCs were potentiated by methyl-6,7
dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), we propose these IPSCs
involve gamma1 subunit-containing GABAAR activation. Therefore, gamma subunit
heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic
transmission in the visual thalamus in a cell-selective manner. We suggest that
activation of gamma1 subunit-containing GABAARs give rise to slower IPSCs in
general, while faster IPSCs tend to be mediated by gamma2 subunit-containing
GABAARs.
PMID- 28420965
TI - Dopamine: A Modulator of Circadian Rhythms in the Central Nervous System.
AB - Circadian rhythms are daily rhythms that regulate many biological processes -
from gene transcription to behavior - and a disruption of these rhythms can lead
to a myriad of health risks. Circadian rhythms are entrained by light, and their
24-h oscillation is maintained by a core molecular feedback loop composed of
canonical circadian ("clock") genes and proteins. Different modulators help to
maintain the proper rhythmicity of these genes and proteins, and one emerging
modulator is dopamine. Dopamine has been shown to have circadian-like activities
in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it
regulates, and is regulated by, clock genes in some of these areas. Thus, it is
likely that dopamine is essential to mechanisms that maintain proper rhythmicity
of these five brain areas. This review discusses studies that showcase different
dopaminergic mechanisms that may be involved with the regulation of these brain
areas' circadian rhythms. Mechanisms include how dopamine and dopamine receptor
activity directly and indirectly influence clock genes and proteins, how
dopamine's interactions with gap junctions influence daily neuronal excitability,
and how dopamine's release and effects are gated by low- and high-pass filters.
Because the dopamine neurons described in this review also release the inhibitory
neurotransmitter GABA which influences clock protein expression in the retina, we
discuss articles that explore how GABA may contribute to the actions of dopamine
neurons on circadian rhythms. Finally, to understand how the loss of function of
dopamine neurons could influence circadian rhythms, we review studies linking the
neurodegenerative disease Parkinson's Disease to disruptions of circadian rhythms
in these five brain areas. The purpose of this review is to summarize growing
evidence that dopamine is involved in regulating circadian rhythms, either
directly or indirectly, in the brain areas discussed here. An appreciation of the
growing evidence of dopamine's influence on circadian rhythms may lead to new
treatments including pharmacological agents directed at alleviating the various
symptoms of circadian rhythm disruption.
PMID- 28420967
TI - Organization and Plasticity of Sodium Channel Expression in the Mouse Olfactory
and Vomeronasal Epithelia.
AB - To understand the molecular basis of neuronal excitation in the mammalian
olfactory system, we conducted a systematic analysis of the organization of
voltage-gated sodium (Nav) channel subunits in the main olfactory epithelium
(MOE) and vomeronasal organ (VNO) of adult mice. We also analyzed changes in Nav
channel expression during development in these two systems and during
regeneration of the MOE. Quantitative PCR shows that Nav1.7 is the predominant
isoform in both adult MOE and VNO. We detected pronounced immunoreactivity for
Nav1.7 and Nav1.3 in axons of olfactory and vomeronasal sensory neurons (VSNs).
Analysis of Nav1.2 and Nav1.6 revealed an unexpected subsystem-specific
distribution. In the MOE, these Nav channels are absent from olfactory sensory
neurons (OSNs) but present in non-neuronal olfactory cell types. In the VNO,
Nav1.2 and Nav1.6 are confined to VSNs, with Nav1.2-immunoreactive somata solely
present in the basal layer of the VNO. The subcellular localization of Nav1.3 and
Nav1.7 in OSNs can change dramatically during periods of heightened plasticity in
the MOE. During the first weeks of development and during regeneration of the
olfactory epithelium following chemical lesion, expression of Nav1.3 and Nav1.7
is transiently enhanced in the somata of mature OSNs. Our results demonstrate a
highly complex organization of Nav channel expression in the mouse olfactory
system, with specific commonalities but also differences between the MOE and the
VNO. On the basis of their subcellular localization, Nav1.3 and Nav1.7 should
play major roles in action potential propagation in both MOE and VNO, whereas
Nav1.2 and Nav1.6 are specific to the function of VSNs. The plasticity of Nav
channel expression in OSNs during early development and recovery from injury
could reflect important physiological requirements in a variety of activity
dependent mechanisms.
PMID- 28420968
TI - Cortical Variability and Challenges for Modeling Approaches.
PMID- 28420969
TI - Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB
Rat Line.
AB - This review article addresses the biological factors that influence: (i) the
acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake;
and (iii) alcohol relapse-like drinking behavior in animals bred for their high
ethanol intake. Data from several rat strains/lines strongly suggest that
catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute
requirement (up 80%-95%) for rats to display ethanol's reinforcing effects and to
initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine
forming salsolinol, a compound that is self-administered. In UChB rats,
salsolinol: (a) generates marked sensitization to the motivational effects of
ethanol; and (b) strongly promotes binge-like drinking. The specificity of
salsolinol actions is shown by the finding that only the R-salsolinol enantiomer
but not S-salsolinol accounted for the latter effects. Inhibition of brain
acetaldehyde synthesis does not influence the maintenance of chronic ethanol
intake. However, a prolonged ethanol withdrawal partly returns the requirement
for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol
relapse-like drinking. Chronic ethanol intake, involving the action of
lipopolysaccharide diffusing from the gut, and likely oxygen radical generated
upon catechol/salsolinol oxidation, leads to oxidative stress and neuro
inflammation, known to potentiate each other. Data show that the administration
of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol
maintenance by 60%-70%, without inhibiting its initial intake. Intra
cerebroventricular administration of mesenchymal stem cells (MSCs), known to
release anti-inflammatory cytokines, to elevate superoxide dismutase levels and
to reverse ethanol-induced hippocampal injury and cognitive deficits, also
inhibited chronic ethanol maintenance; further, relapse-like ethanol drinking was
inhibited up to 85% for 40 days following intracerebral stem cell administration.
Thus: (i) ethanol must be metabolized intracerebrally into acetaldehyde, and
further into salsolinol, which appear responsible for promoting the acquisition
of the early reinforcing effects of ethanol; (ii) acetaldehyde is not responsible
for the maintenance of chronic ethanol intake, while other mechanisms are
indicated; (iii) the systemic administration of NAC, a strong antioxidant
markedly inhibits the maintenance of chronic ethanol intake; and (iv) the intra
cerebroventricular administration of anti-inflammatory and antioxidant MSCs
inhibit both the maintenance of chronic ethanol intake and relapse-like drinking.
PMID- 28420970
TI - Single-Session Anodal tDCS with Small-Size Stimulating Electrodes Over
Frontoparietal Superficial Sites Does Not Affect Motor Sequence Learning.
AB - Due to the potential of anodal transcranial direct current stimulation (a-tDCS)
for enhancement of fine sequenced movements and increasing interest in achieving
high level of fine movements in the trained and untrained hands especially at
initial stage of learning, we designed this study to investigate whether the
application of single-session a-tDCS with small-size stimulating electrodes over
FPN sites, such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex
(M1) or posterior parietal cortex (PPC) could enhance sequence learning with the
trained hand and these effects are transferred into the untrained hand or not. A
total of 51 right-handed healthy participants were randomly assigned to one of
the four stimulation groups: a-tDCS of left M1, DLPFC, PPC, or sham. Stimulation
was applied for 20 min during a sequential visual isometric pinch task (SVIPT).
Eight blocks of training using SVIPT were completed with the right hand during
stimulation. Two blocks of sequence training with each hand were performed by
participants as assessment blocks at three time points: baseline, 15 min and one
day following the intervention. Behavioral outcomes including movement time,
error rate and skill were assessed in all assessment blocks across three time
points. We also measured corticospinal excitability, short-interval intracortical
inhibition, and intracortical facilitation using single- and paired-pulse
transcranial magnetic stimulation. The results indicated that the behavioral
outcomes were significantly improved with the right trained hand, but this
learning effect was not modulated by a-tDCS with small-size stimulating
electrodes over the FPN. Transfer of learning into the untrained hand was
observed in all four groups for movement time but not for the error rate or
skill. Our results suggest that sequential learning in SVIPT and its transfer
into the untrained hand were not sensitive to a single-session a-tDCS with small
size stimulating electrodes over left M1, DLPFC or PPC in young healthy
participants.
PMID- 28420971
TI - Dynamic Increase in Corticomuscular Coherence during Bilateral, Cyclical Ankle
Movements.
AB - In humans, the midline primary motor cortex is active during walking. However,
the exact role of such cortical participation is unknown. To delineate the role
of the primary motor cortex in walking, we examined whether the primary motor
cortex would activate leg muscles during movements that retained specific
requirements of walking (i.e., locomotive actions). We recorded
electroencephalographic and electromyographic signals from 15 healthy, young men
while they sat and performed bilateral, cyclical ankle movements. During
dorsiflexion, near-20-Hz coherence increased cyclically between the midline
primary motor cortex and the co-contracting antagonistic pair (i.e., tibialis
anterior and medial gastrocnemius muscles) in both legs. Thus, we have shown that
dynamic increase in corticomuscular coherence, which has been observed during
walking, also occurs during simple bilateral cyclical movements of the feet. A
possible mechanism for such coherence is corticomuscular communication, in which
the primary motor cortex participates in the control of movement. Furthermore,
because our experimental task isolated certain locomotive actions, the observed
coherence suggests that the human primary motor cortex may participate in these
actions (i.e., maintaining a specified movement frequency, bilaterally
coordinating the feet, and stabilizing the posture of the feet). Additional
studies are needed to identify the exact cortical and subcortical interactions
that cause corticomuscular coherence and to further delineate the functional role
of the primary motor cortex during bilateral cyclical movements such as walking.
PMID- 28420972
TI - Multi-modal, Multi-measure, and Multi-class Discrimination of ADHD with
Hierarchical Feature Extraction and Extreme Learning Machine Using Structural and
Functional Brain MRI.
AB - Structural and functional MRI unveil many hidden properties of the human brain.
We performed this multi-class classification study on selected subjects from the
publically available attention deficit hyperactivity disorder ADHD-200 dataset of
patients and healthy children. The dataset has three groups, namely, ADHD
inattentive, ADHD combined, and typically developing. We calculated the global
averaged functional connectivity maps across the whole cortex to extract
anatomical atlas parcellation based features from the resting-state fMRI (rs
fMRI) data and cortical parcellation based features from the structural MRI
(sMRI) data. In addition, the preprocessed image volumes from both of these
modalities followed an ANOVA analysis separately using all the voxels. This study
utilized the average measure from the most significant regions acquired from
ANOVA as features for classification in addition to the multi-modal and multi
measure features of structural and functional MRI data. We extracted most
discriminative features by hierarchical sparse feature elimination and selection
algorithm. These features include cortical thickness, image intensity, volume,
cortical thickness standard deviation, surface area, and ANOVA based features
respectively. An extreme learning machine performed both the binary and multi
class classifications in comparison with support vector machines. This article
reports prediction accuracy of both unimodal and multi-modal features from test
data. We achieved 76.190% (p < 0.0001) classification accuracy in multi-class
settings as well as 92.857% (p < 0.0001) classification accuracy in binary
settings. In addition, we found ANOVA-based significant regions of the brain that
also play a vital role in the classification of ADHD. Thus, from a clinical
perspective, this multi-modal group analysis approach with multi-measure features
may improve the accuracy of the ADHD differential diagnosis.
PMID- 28420973
TI - No Overt Effects of a 6-Week Exergame Training on Sensorimotor and Cognitive
Function in Older Adults. A Preliminary Investigation.
AB - Several studies investigating the relationship between physical activity and
cognition showed that exercise interventions might have beneficial effects on
working memory, executive functions as well as motor fitness in old adults.
Recently, movement based video games (exergames) have been introduced to have the
capability to improve cognitive function in older adults. Healthy aging is
associated with a loss of cognitive, as well as sensorimotor functions. During
exergaming, participants are required to perform physical activities while being
simultaneously surrounded by a cognitively challenging environment. However, only
little is known about the impact of exergame training interventions on a broad
range of motor, sensory, and cognitive skills. Therefore, the present study aims
at investigating the effects of an exergame training over 6 weeks on cognitive,
motor, and sensory functions in healthy old participants. For this purpose, 30
neurologically healthy older adults were randomly assigned to either an
experimental (ETG, n = 15, 1 h training, twice a week) or a control group (NTG, n
= 15, no training). Several cognitive tests were performed before and after
exergaming in order to capture potential training-induced effects on processing
speed as well as on executive functions. To measure the impact of exergaming on
sensorimotor performance, a test battery consisting of pinch and grip force of
the hand, tactile acuity, eye-hand coordination, flexibility, reaction time,
coordination, and static balance were additionally performed. While we observed
significant improvements in the trained exergame (mainly in tasks that required a
high load of coordinative abilities), these gains did not result in differential
performance improvements when comparing ETG and NTG. The only exergaming-induced
difference was a superior behavioral gain in fine motor skills of the left hand
in ETG compared to NTG. In an exploratory analysis, within-group comparison
revealed improvements in sensorimotor and cognitive tasks (ETG) while NTG only
showed an improvement in a static balance test. Taken together, the present study
indicates that even though exergames might improve gaming performance, our
behavioral assessment was probably not sensitive enough to capture exergaming
induced improvements. Hence, we suggest to use more tailored outcome measures in
future studies to assess potential exergaming-induced changes.
PMID- 28420974
TI - Thinking on Treating Echolalia in Aphasia: Recommendations and Caveats for Future
Research Directions.
PMID- 28420976
TI - Improving Robot Motor Learning with Negatively Valenced Reinforcement Signals.
AB - Both nociception and punishment signals have been used in robotics. However, the
potential for using these negatively valenced types of reinforcement learning
signals for robot learning has not been exploited in detail yet. Nociceptive
signals are primarily used as triggers of preprogrammed action sequences.
Punishment signals are typically disembodied, i.e., with no or little relation to
the agent-intrinsic limitations, and they are often used to impose behavioral
constraints. Here, we provide an alternative approach for nociceptive signals as
drivers of learning rather than simple triggers of preprogrammed behavior.
Explicitly, we use nociception to expand the state space while we use punishment
as a negative reinforcement learning signal. We compare the performance-in terms
of task error, the amount of perceived nociception, and length of learned action
sequences-of different neural networks imbued with punishment-based reinforcement
signals for inverse kinematic learning. We contrast the performance of a version
of the neural network that receives nociceptive inputs to that without such a
process. Furthermore, we provide evidence that nociception can improve learning
making the algorithm more robust against network initializations-as well as
behavioral performance by reducing the task error, perceived nociception, and
length of learned action sequences. Moreover, we provide evidence that
punishment, at least as typically used within reinforcement learning
applications, may be detrimental in all relevant metrics.
PMID- 28420977
TI - Development and Training of a Neural Controller for Hind Leg Walking in a Dog
Robot.
AB - Animals dynamically adapt to varying terrain and small perturbations with
remarkable ease. These adaptations arise from complex interactions between the
environment and biomechanical and neural components of the animal's body and
nervous system. Research into mammalian locomotion has resulted in several neural
and neuro-mechanical models, some of which have been tested in simulation, but
few "synthetic nervous systems" have been implemented in physical hardware models
of animal systems. One reason is that the implementation into a physical system
is not straightforward. For example, it is difficult to make robotic actuators
and sensors that model those in the animal. Therefore, even if the sensorimotor
circuits were known in great detail, those parameters would not be applicable and
new parameter values must be found for the network in the robotic model of the
animal. This manuscript demonstrates an automatic method for setting parameter
values in a synthetic nervous system composed of non-spiking leaky integrator
neuron models. This method works by first using a model of the system to
determine required motor neuron activations to produce stable walking. Parameters
in the neural system are then tuned systematically such that it produces similar
activations to the desired pattern determined using expected sensory feedback. We
demonstrate that the developed method successfully produces adaptive locomotion
in the rear legs of a dog-like robot actuated by artificial muscles. Furthermore,
the results support the validity of current models of mammalian locomotion. This
research will serve as a basis for testing more complex locomotion controllers
and for testing specific sensory pathways and biomechanical designs.
Additionally, the developed method can be used to automatically adapt the neural
controller for different mechanical designs such that it could be used to control
different robotic systems.
PMID- 28420975
TI - Beta Band Corticomuscular Drive Reflects Muscle Coordination Strategies.
AB - During force production, hand muscle activity is known to be coherent with
activity in primary motor cortex, specifically in the beta-band (15-30 Hz)
frequency range. It is not clear, however, if this coherence reflects the control
strategy selected by the nervous system for a given task, or if it instead
reflects an intrinsic property of cortico-spinal communication. Here, we measured
corticomuscular and intermuscular coherence between muscles of index finger and
thumb while a two-finger pinch grip of identical net force was applied to objects
which were either stable (allowing synergistic activation of finger muscles) or
unstable (requiring individuated finger control). We found that beta-band
corticomuscular coherence with the first dorsal interosseous (FDI) and abductor
pollicis brevis (APB) muscles, as well as their beta-band coherence with each
other, was significantly reduced when individuated control of the thumb and index
finger was required. We interpret these findings to show that beta-band coherence
is reflective of a synergistic control strategy in which the cortex binds task
related motor neurons into functional units.
PMID- 28420978
TI - Resting State fMRI Reveals Increased Subthalamic Nucleus and Sensorimotor Cortex
Connectivity in Patients with Parkinson's Disease under Medication.
AB - Functional connectivity (FC) between the subthalamic nucleus (STN) and the
sensorimotor cortex is increased in off-medication patients with Parkinson's
disease (PD). However, the status of FC between STN and sensorimotor cortex in on
medication PD patients remains unclear. In this study, resting state functional
magnetic resonance imaging was employed on 31 patients with PD under medication
and 31 healthy controls. Two-sample t-test was used to study the change in FC
pattern of the STN, the FC strength of the bilateral STN was correlated with
overall motor symptoms, while unilateral STN was correlated with offside motor
symptoms. Both bilateral and right STN showed increased FC with the right
sensorimotor cortex, whereas only right STN FC was correlated with left-body
rigidity scores in all PD patients. An additional subgroup analysis was performed
according to the ratio of mean tremor scores and mean postural instability and
gait difficulty (PIGD) scores, only the PIGD subgroup showed the increased FC
between right STN and sensorimotor cortex under medication. Increased FC between
the STN and the sensorimotor cortex was found, which was related to motor symptom
severity in on-medication PD patients. Anti-PD drugs may influence the
hyperdirect pathway to alleviate motor symptoms with the more effect on the
tremor subtype.
PMID- 28420979
TI - Evidence for a Selectively Regulated Prioritization Shift Depending on Walking
Situations in Older Adults.
AB - Background: Older adults have increased risks of balance issues and falls when
walking and performing turns in daily situations. Changes of prioritization
during different walking situations associated with dual tasking may contribute
to these deficits. The objective of this study was therefore to investigate
whether older adults demonstrate changes of prioritization during different
walking paths. Methods: In total, 1,054 subjects with an age range from 50 to 83
years were selected from the first follow-up visit of the TREND (Tuebinger
evaluation of Risk factors for Early detection of Neurodegenerative Disorders)
study. They were classified according to their performance on the Trail Making
Test (TMT) into good and poor TMT performers (based on recent results showing
that cognitive flexibility affects prioritization strategies during straight
walking). Absolute dual-task performance and relative dual-task costs (DTC,
relative performance under dual-task conditions compared with single-task
conditions) were assessed in two paradigms: walking while subtracting serial 7 s
and walking while checking boxes on a clipboard. Both tasks were performed on
straight and curved paths. Results: Overall, the poor TMT performers group
performed worse in all single and dual tasks. Interestingly, the relative change
in performance measured by dual-task costs differed in the groups between the two
walking paths. On straight paths, poor TMT performers had a similar DTC of
walking to that of good performers (p = 0.10) but had a significantly lower DTC
of subtracting (p = 0.02). On curved paths, poor performers had a similar DTC of
subtracting (p = 0.10), but their DTC of walking was significantly higher (p <
0.0001). Conclusion: Given that walking on curved paths is considered more
difficult than that on straight paths and that the serial subtracting dual task
is more difficult than the box checking dual task, this study in older adults
provides evidence for the existence of a (walking) situation-dependent change of
prioritization. If confirmed in other studies, situation-dependent change of
prioritization should be included as a potential factor contributing to gait and
balance impairments, and increased fall risk in older adults.
PMID- 28420980
TI - Loss of Melanopsin-Expressing Ganglion Cell Subtypes and Dendritic Degeneration
in the Aging Human Retina.
AB - In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other
things, involved in several non-image-forming visual functions, including light
entrainment of circadian rhythms. Considering the profound impact of aging on
visual function and ophthalmic diseases, here we evaluate changes in mRGCs
throughout the life span in humans. In 24 post-mortem retinas from anonymous
human donors aged 10-81 years, we assessed the distribution, number and
morphology of mRGCs by immunostaining vertical retinal sections and whole-mount
retinas with antibodies against melanopsin. Human retinas showed melanopsin
immunoreactivity in the cell body, axon and dendrites of a subset of ganglion
cells at all ages tested. Nearly half of the mRGCs (51%) were located within the
ganglion cell layer (GCL), and stratified in the outer (M1, 12%) or inner (M2,
16%) margin of the inner plexiform layer (IPL) or in both plexuses (M3, 23%). M1
and M2 cells conformed fairly irregular mosaics, while M3 cell distribution was
slightly more regular. The rest of the mRGCs were more regularly arranged in the
inner nuclear layer (INL) and stratified in the outer margin of the IPL (M1d,
49%). The quantity of each cell type decrease after age 70, when the total number
of mRGCs was 31% lower than in donors aged 30-50 years. Moreover, in retinas with
an age greater than 50 years, mRGCs evidenced a decrease in the dendritic area
that was both progressive and age-dependent, as well as fewer branch points and
terminal neurite tips per cell and a smaller Sholl area. After 70 years of age,
the distribution profile of the mRGCs was closer to a random pattern than was
observed in younger retinas. We conclude that advanced age is associated with a
loss in density and dendritic arborization of the mRGCs in human retinas,
possibly accounting for the more frequent occurrence of circadian rhythm
disorders in elderly persons.
PMID- 28420981
TI - Age-Related Difference in Functional Brain Connectivity of Mastication.
AB - The age-related decline in motor function is associated with changes in intrinsic
brain signatures. Here, we investigated the functional connectivity (FC)
associated with masticatory performance, a clinical index evaluating general
masticatory function. Twenty-six older adults (OA) and 26 younger (YA) healthy
adults were recruited and assessed using the masticatory performance index (MPI)
and resting-state functional magnetic resonance imaging (rs-fMRI). We analyzed
the rs-fMRI FC network related to mastication, which was constructed based on 12
bilateral mastication-related brain regions according to the literature. For the
OA and the YA group, we identified the mastication-related hubs, i.e., the nodes
for which the degree centrality (DC) was positively correlated with the MPI. For
each pair of nodes, we identified the inter-nodal link for which the FC was
positively correlated with the MPI. The network analysis revealed that, in the YA
group, the FC between the sensorimotor cortex, the thalamus (THA) and the
cerebellum was positively correlated with the MPI. Consistently, the cerebellum
nodes were defined as the mastication-related hubs. In contrast, in the OA group,
we found a sparser connection within the sensorimotor regions and cerebellum and
a denser connection across distributed regions, including the FC between the
superior parietal lobe (SPL), the anterior insula (aINS) and the dorsal anterior
cingulate cortex (dACC). Compared to the YA group, the network of the OA group
also comprised more mastication-related hubs, which were spatially distributed
outside the sensorimotor regions, including the right SPL, the right aINS, and
the bilateral dACC. In general, the findings supported the hypothesis that in OA,
higher masticatory performance is associated with a widespread pattern of
mastication-related hubs. Such a widespread engagement of multiple brain regions
associated with the MPI may reflect an increased demand in sensorimotor
integration, attentional control and monitoring for OA to maintain good
mastication.
PMID- 28420982
TI - Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage.
AB - Aging has long been considered as the main risk factor for several
neurodegenerative disorders including a large group of diseases known as
tauopathies. Even though neurofibrillary tangles (NFTs) have been examined as the
main histopathological hallmark, they do not seem to play a role as the toxic
entities leading to disease. Recent studies suggest that an intermediate form of
tau, prior to NFT formation, the tau oligomer, is the true toxic species.
However, the mechanisms by which tau oligomers trigger neurodegeneration remain
unknown. This review summarizes recent findings regarding the role of tau
oligomers in disease, including release from cells, propagation from affected to
unaffected brain regions, uptake into cells, and toxicity via mitochondrial
dysfunction. A greater understanding of tauopathies may lead to future
advancements in regards to prevention and treatment.
PMID- 28420983
TI - Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects
with Parkinson's Disease-Associated LRRK2 Gene Mutations.
AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent
cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2
mutation, G2019S, induces increased production of reactive oxygen species in
vitro. We therefore hypothesized that individuals with PD-associated LRRK2
mutations might have increased concentrations of oxidative stress markers and/or
decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We
measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8
OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD
patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control
subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8
ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between
groups. 8-ISO was negatively correlated, and TAC was positively correlated, with
Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects.
Correlations in both groups of PD patients between the two oxidative stress
markers and Unified Parkinson Disease Rating Scale Total scores were weak, while
TAC was negatively correlated with these scores. These findings suggest that
oxidative stress may be increased in the CNS in healthy individuals with PD
associated LRRK2 mutations. Further, TAC may decrease in the CNS with the
progression of PD, and when cognitive impairment is present regardless of the
presence or absence of PD.
PMID- 28420984
TI - Potential Roles of Serum Caveolin-3 Levels in Patients with Atrial Fibrillation.
AB - Objective: To explore serum caveolin-3 (Cav-3) levels in patients with atrial
fibrillation (AF) and to evaluate the role of Cav-3 as a biomarker for AF and
incident heart failure (HF). Methods: Three hundred and five patients were
enrolled in the study and divided into three groups: sinus rhythm (Group SR),
paroxysmal AF (Group paAF), and persistent AF (Group peAF). Serum Cav-3
concentrations were measured by enzyme-linked immunosorbent assay at baseline.
Clinical characteristics, and laboratory data were collected during
hospitalization, and a follow-up of 12-months was carried out. Results: Serum Cav
3 concentrations were significantly decreased on the Group SR and the highest
concentrations of Cav-3 in patients were found on the Group peAF (516.7 +/- 274.0
vs. 609.3 +/- 287.0 vs. 688.3 +/- 264.6 ng/L, P < 0.05). Left atrial diameter
(LAD) in the Group peAF was significantly higher than in the Group paAF, and the
Group SR had significantly lower LAD than the Group paAF and Group peAF. The
risks of new-onset HF in the Group SR, Group paAF, and Group peAF were 8.1, 14.5,
and 28.6%, respectively. There was a significant difference between the Group
peAF and the other two groups. Serum Cav-3 concentrations were trisected in AF
participants (lower tertile: <=498, middle tertile: >498-703, upper tertile:
>=703). In further tertile studies, subjects in the lower tertile of Cav-3
concentrations were more likely to become paroxysmal AF and had much lower LAD (P
< 0.05). And in the middle and upper tertiles, participants with AF tended to
suffer from HF compared to the lower group (P < 0.05). Conclusion: We provide
evidence that Cav-3 has a significant meaning in AF patients. The levels of Cav-3
may be related to the LAD and new-onset HF.
PMID- 28420985
TI - Mapping Dorsal and Ventral Caudate in Older Adults: Method and Validation.
AB - The caudate nucleus plays important roles in cognition and affect. Depending on
associated connectivity and function, the caudate can be further divided into
dorsal and ventral aspects. Dorsal caudate, highly connected to dorsolateral
prefrontal cortex (DLPFC), is implicated in executive function and working
memory; ventral caudate, more interconnected with the limbic system, is
implicated in affective functions such as pain processing. Clinically, certain
brain disorders are known to differentially impact dorsal and ventral caudate.
Thus, precise parcellation of caudate has both basic and clinical neuroscience
significance. In young adults, past work has combined resting-state fMRI
functional connectivity with clustering algorithms to define dorsal and ventral
caudate. Whether the same approach is effective in older adults and how to
validate the parcellation results have not been considered. We addressed these
problems by obtaining resting-state fMRI data from 56 older non-demented adults
(age: 69.07 +/- 5.92 years and MOCA: 25.71 +/- 2.46) along with a battery of
cognitive and clinical assessments. Connectivity from each voxel of caudate to
the rest of the brain was computed using cross correlation. Applying the K-means
clustering algorithm to the connectivity patterns with K = 2 yielded two
substructures within caudate, which agree well with previously reported dorsal
and ventral divisions of caudate. Furthermore, dorsal-caudate-seeded functional
connectivity was shown to be more strongly associated with working memory and
fluid reasoning composite scores, whereas ventral-caudate-seeded functional
connectivity more strongly associated with pain and fatigue severity. These
results demonstrate that dorsal and ventral caudate can be reliably identified by
combining resting-state fMRI and clustering algorithms in older adults.
PMID- 28420986
TI - Modulation of Microglial Activity by Rho-Kinase (ROCK) Inhibition as Therapeutic
Strategy in Parkinson's Disease and Amyotrophic Lateral Sclerosis.
AB - Neurodegenerative diseases are characterized by the progressive degeneration of
neurons in the central and peripheral nervous system (CNS, PNS), resulting in a
reduced innervation of target structures and a loss of function. A shared
characteristic of many neurodegenerative diseases is the infiltration of
microglial cells into affected brain regions. During early disease stages
microglial cells often display a rather neuroprotective phenotype, but switch to
a more pro-inflammatory neurotoxic phenotype in later stages of the disease,
contributing to the neurodegeneration. Activation of the Rho kinase (ROCK)
pathway appears to be instrumental for the modulation of the microglial
phenotype: increased ROCK activity in microglia mediates mechanisms of the
inflammatory response and is associated with improved motility, increased
production of reactive oxygen species (ROS) and release of inflammatory
cytokines. Recently, several studies suggested inhibition of ROCK signaling as a
promising treatment option for neurodegenerative diseases. In this review
article, we discuss the contribution of microglial activity and phenotype switch
to the pathophysiology of Parkinson's disease (PD) and Amyotrophic lateral
sclerosis (ALS), two devastating neurodegenerative diseases without disease
modifying treatment options. Furthermore, we describe how ROCK inhibition can
influence the microglial phenotype in disease models and explore ROCK inhibition
as a future treatment option for PD and ALS.
PMID- 28420987
TI - Curcumin Ameliorates Cisplatin-Induced Nephrotoxicity and Potentiates Its
Anticancer Activity in SD Rats: Potential Role of Curcumin in Breast Cancer
Chemotherapy.
AB - Breast malignant neoplastic disease is one of the most complex diseases, as it is
a multifactorial disease in which virtually all the targets are instantly or
indirectly inter-reliant on each other. Cisplatin (CIS), an inorganic
antineoplastic agent is widely utilized in the treatment of various solid tumors
including breast cancer. Despite everything, its clinical use is limited, due to
ototoxicity, peripheral neuropathy, and nephrotoxicity. The present work was
directed to assess the combined result of curcumin (CUR) and CIS in 7, 12
dimethyl benz[a]anthracene (DMBA) induced breast cancer in rats and the
prevention of nephrotoxicity induced by the latter. CIS-induced nephrotoxicity
was assessed by change in body weight, kidney weight, altered levels of BUN,
creatinine, TNF-alpha, IL-6, IL-8, IL-10, and histopathology of the kidney.
Anticancer activity was assessed by measurement of tumor weight, tumor volume, %
tumor inhibition, levels of PPAR-gamma, and BDNF in mammary tumors and
histopathology of mammary tumors. CUR pre-treatment mitigated nephrotoxicity by
reducing the inflammatory markers (TNF-alpha, IL-6, and IL-8; p < 0.001).
Further, it reduced mammary cancer via increasing the expression of PPAR-gamma (p
< 0.001) and decreasing the expression of BDNF (p < 0.001) in mammary tumors. It
also reduced tumor volume, further postulating that CUR might adjunct the
anticancer activity of the CIS. To the best of our knowledge, this is the first
report, which showed that CUR ameliorated CIS-induced nephrotoxicity and improved
its anticancer activity in DMBA induced breast cancer in female Sprague-Dawley
rats.
PMID- 28420989
TI - FDA Facilitated Regulatory Pathways: Visualizing Their Characteristics,
Development, and Authorization Timelines.
AB - The US Food and Drug Administration (FDA) has four facilitated regulatory
pathways (FRPs): Fast Track (FT), Breakthrough Therapy (BTD), Priority Review
(PR), and Accelerated Approval (AA). Only PR specifies an expedited review
timeline (6 months). We sought to determine to what extent the combination of two
or more FRPs influenced development and approval times. We developed a "metro
map" to illustrate FRP elements and their influence on review times. We assessed
125 new active substances (approved January 2013 to December 2015) 74 of which
used one or more FRPs. For these 74, development times ranged from 1,458 (BTD +
PR + AA) to 3,515 days (PR). PR alone had a median approval time of 242 days. The
most common combination was FT + PR (median approval 292 days, n = 21). The
fastest approval times were for PR + FT + BTD + AA (145 days) and PR + BTD + AA
(166 days). Our findings support the combination of FRPs for shortening
development and review times beyond that provided by PR alone.
PMID- 28420990
TI - Managed Entry Agreements for Oncology Drugs: Lessons from the European Experience
to Inform the Future.
AB - Objectives: The aim of this study is to conduct an analysis on the regulation and
application of managed entry agreements (MEA) for oncology drugs across different
European countries. Methods: Literature search and document analysis were
performed between September 2015 and June 2016 to collect information on the
regulatory framework and practice of MEA in Belgium, The Netherlands, Scotland,
England and Wales, Sweden, Italy, Czech Republic and France. An overview of the
content and typology of MEA applied for oncology drugs between 2008 and 2015 was
generated based on publically available sources and contributions by national
health authorities. Semi-structured interviews were conducted with
representatives of national health authorities involved in the management or
negotiation of MEA. Results: The application of MEA differs across countries and
across different indications for the same drug. Financial based agreements are
prevailing due to their simplicity compared to performance-based agreements.
Performance-based agreements are less commonly applied in the European countries
except for Italy. In the Netherlands, application of performance-based agreements
was stopped due to their inability to deal with dynamics in the market, which is
highly relevant for oncology drugs. Conclusions: MEA constitute a common policy
tool that public payers in European countries use to ensure early access to
highly priced oncology drugs. In light of strengths and weaknesses observed for
MEA and the expected developments in the oncology area, the importance of MEA is
likely to grow in the future.
PMID- 28420991
TI - Gabapentin Attenuates Ocular Inflammation: In vitro and In vivo Studies.
AB - To investigate the effects of gabapentin, a structural analog of gamma-amino
butyric acid (GABA), on the inflammatory response of lipopolysaccharide (LPS)
stimulated rabbit corneal cells (SIRC) and on endotoxin-induced uveitis (EIU) in
rabbits. We investigated the LPS-induced expression of several inflammatory
mediators, such as TNF-alpha, IL-1beta, cPLA2, COX-2, and PGE2 in the SIRC cells
with or without gabapentin treatment. Gabapentin treatment significantly (p <
0.05) attenuated cytokines production, cPLA2 activation, COX-2 expression, and
PGE2 levels in SIRC. EIU was induced by an intraocular injection of 0.1 MUg of
LPS in albino rabbit eye. After 7 and 24 h from LPS injection clinical signs of
ocular inflammation were examined by slit lamp with or without topical treatment
of 0.5% gabapentin. Tears, aqueous, cornea, conjunctiva, and iris-ciliary body
were collected and inflammatory biomarkers assessed. Topical treatment with
gabapentin significantly (p < 0.05) reduced clinical signs and biomarkers of
inflammation compared with the LPS group both at 7 and 24 h. In conclusion, the
results generated in the present study suggest that ophthalmic formulation based
on gabapentin may be useful in the treatment of inflammatory conditions
associated to ocular pain such as uveitis, and that clinical studies to evaluate
this possibility may be warranted.
PMID- 28420988
TI - Heme as a Target for Therapeutic Interventions.
AB - Heme is a complex of iron and the tetrapyrrole protoporphyrin IX with essential
functions in aerobic organisms. Heme is the prosthetic group of hemoproteins such
as hemoglobin and myoglobin, which are crucial for reversible oxygen binding and
transport. By contrast, high levels of free heme, which may occur in various
pathophysiological conditions, are toxic via pro-oxidant, pro-inflammatory and
cytotoxic effects. The toxicity of heme plays a major role for the pathogenesis
of prototypical hemolytic disorders including sickle cell disease and malaria.
Moreover, there is increasing appreciation that detrimental effects of heme may
also be critically involved in diseases, which usually are not associated with
hemolysis such as severe sepsis and atherosclerosis. In mammalians homeostasis of
heme and its potential toxicity are primarily controlled by two physiological
systems. First, the scavenger protein hemopexin (Hx) non-covalently binds
extracellular free heme with high affinity and attenuates toxicity of heme in
plasma. Second, heme oxygenases (HOs), in particular the inducible HO isozyme, HO
1, can provide antioxidant cytoprotection via enzymatic degradation of
intracellular heme. This review summarizes current knowledge on the
pathophysiological role of heme for various diseases as demonstrated in
experimental animal models and in humans. The functional significance of Hx and
HOs for the regulation of heme homeostasis is highlighted. Finally, the
therapeutic potential of pharmacological strategies that apply Hx and HO-1 in
various clinical settings is discussed.
PMID- 28420992
TI - Deficient Adipogenesis of Scleroderma Patient and Healthy African American
Monocytes.
AB - Monocytes from systemic sclerosis (SSc, scleroderma) patients and healthy African
Americans (AA) are deficient in the regulatory protein caveolin-1 leading to
enhanced migration toward chemokines and fibrogenic differentiation. While dermal
fibrosis is the hallmark of SSc, loss of subcutaneous adipose tissue is a lesser
known feature. To better understand the etiology of SSc and the predisposition of
AA to SSc, we studied the adipogenic potential of SSc and healthy AA monocytes.
The ability of SSc and healthy AA monocytes to differentiate into adipocyte-like
cells (ALC) is inhibited compared to healthy Caucasian (C) monocytes. We
validated that monocyte-derived ALCs are distinct from macrophages by flow
cytometry and immunocytochemistry. Like their enhanced fibrogenic
differentiation, their inhibited adipogenic differentiation is reversed by the
caveolin-1 scaffolding domain peptide (CSD, a surrogate for caveolin-1). The
altered differentiation of SSc and healthy AA monocytes is additionally regulated
by peroxisome proliferator-activated receptor gamma (PPARgamma) which is also
present at reduced levels in these cells. In vivo studies further support the
importance of caveolin-1 and PPARgamma in fibrogenesis and adipogenesis. In SSc
patients, healthy AA, and mice treated systemically with bleomycin, adipocytes
lose caveolin-1 and PPARgamma and the subcutaneous adipose layer is diminished.
CSD treatment of these mice leads to a reappearance of the caveolin
1+/PPARgamma+/FABP4+ subcutaneous adipose layer. Moreover, many of these
adipocytes are CD45+, suggesting they are monocyte derived. Tracing experiments
with injected EGFP+ monocytes confirm that monocytes contribute to the repair of
the adipose layer when it is damaged by bleomycin treatment. Our observations
strongly suggest that caveolin-1 and PPARgamma work together to maintain a
balance between the fibrogenic and adipogenic differentiation of monocytes, that
this balance is altered in SSc and in healthy AA, and that monocytes make a major
contribution to the repair of the adipose layer.
PMID- 28420993
TI - Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury
through Autophagic Regulation.
AB - The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly
increasing around the world and this disease is a major contributor to global
morbidity and mortality. It is known that regulation of programmed cell death
including apoptosis and autophagy reduces the impact of myocardial IR injury. In
this study, the cardioprotective effects and underlying mechanisms of Phellinus
linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal
mushroom, were examined in rats subjected to myocardial IR injury. The left main
coronary artery of rats was ligated for 1 h and reperfused for 3 h. The
arrhythmia levels were monitored during the entire process and the infarct size
was evaluated after myocardial IR injury. Furthermore, the expression levels of
proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL
mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to
myocardial IR injury. PLM also significantly decreased myocardial infarct size
and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM
administration resulted in decreased caspase 3 and caspase 9 activation and
increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR
level was reduced. Becline-1 and p62 levels decreased. These findings suggest
that PLM is effective in protecting the myocardium against IR injury. The
mechanism involves mediation through suppressed pro-apoptotic signaling and
regulation of autophagic signaling, including stimulation of AMPK-dependent
pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of
protective autophagy and inhibition of excessive autophagy.
PMID- 28420994
TI - Scaffold Diversity of Fungal Metabolites.
AB - Many drug discovery projects rely on commercial compounds to discover active
leads. However, current commercial libraries, with mostly synthetic compounds,
access a small fraction of the possible chemical diversity. Natural products, in
contrast, possess a vast structural diversity and have proven to be an
outstanding source of new drugs. Several chemoinformatic analyses of natural
products have demonstrated their diversity and structural complexity. However, to
our knowledge, the scaffold content and structural diversity of fungal secondary
metabolites have never been studied. Herein, the scaffold diversity of 223 fungal
metabolites was measured and compared to the diversity of approved drugs and
commercial libraries for HTS containing natural, synthetic, and semi-synthetic
compounds. In addition, the global diversity of the fungal isolates was assessed
and compared to other reference data sets using Consensus Diversity Plots, a
chemoinformatic tool recently developed. It was concluded that fungal secondary
metabolites are cyclic systems with few ramifications and more diverse than the
commercial libraries with natural products and semi-synthetic compounds. The
fungal metabolites data set was one of the most structurally diverse, containing
a large proportion of different and unique scaffolds not found in the other
compound data sets including ChEMBL. Therefore, fungal metabolites offer a rich
source of molecules suited for identifying diverse candidates for drug discovery.
PMID- 28420995
TI - Quantum Dots-siRNA Nanoplexes for Gene Silencing in Central Nervous System Tumor
Cells.
AB - RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a
promising approach for cancer gene therapy. However, owing to the lack of safe
and efficient carriers, the application of RNAi for clinical use is still very
limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide
quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These
CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable
nanoplex (QD-PEI) and subsequently they are used for siRNA loading which
specially targets human telomerase reverse transcriptase (TERT). High gene
transfection efficiency (>80%) was achieved on two glioblastoma cell lines, U87
and U251. The gene expression level (49.99 +/- 10.23% for U87, 43.28 +/- 9.66%
for U251) and protein expression level (51.58 +/- 7.88% for U87, 50.69 +/- 7.59%
for U251) of TERT is observed to decrease substantially after transfecting the
tumor cells for 48 h. More importantly, the silencing of TERT gene expression
significantly suppressed the proliferation of glioblastoma cells. No obvious
cytotoxicity from these QD-PEI nanoplexes were observed over at 10 times of the
transfected doses. Based on these results, we envision that QDs engineered here
can be used as a safe and efficient gene nanocarrier for siRNA delivery and a
promising tool for future cancer gene therapy applications.
PMID- 28420996
TI - Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive
System in Male Mice.
AB - There is a global increase in the popularity of water-pipe tobacco smoking
including in Europe and North America. Nevertheless, little is known about the
male reproductive effects of water-pipe smoke (WPS), especially after long-term
exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for
6 months. Control mice were exposed to air-only for the same period of time.
Twenty-four hours after the last exposure, testicular histopathology, and markers
of inflammation and oxidative stress, and the tyrosine-protein kinase vascular
endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular
homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone
(LH) concentrations were also measured. Chronic WPS exposure induced a
significant decrease of testosterone and estradiol, and a slight but significant
increase of LH. Glutathione reductase, catalase, and ascorbic acid were
significantly decreased following WPS exposure. Plasma concentration of leptin
was significantly decreased by WPS exposure, whereas that of tumor necrosis
factor alpha and interleukin 6 was significantly increased. Histopathological
analysis of the testes revealed the presence of a marked reduction in the
diameter of the seminiferous tubules with reduced spermatogenesis. Transmission
electron microscopy examination showed irregular thickening and wrinkling of the
basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1
was overexpressed in the testis of the mice exposed to WPS and was not detected
in the control. The urine concentration of cotinine, the predominant metabolite
of nicotine, was significantly increased in the WPS-exposed group compared with
the control group. We conclude that chronic exposure to WPS induces damaging
effects to the reproductive system in male mice. If this can be confirmed in
humans, it would be an additional concern to an already serious public health
problem, especially with the increased use of WPS use all over the world,
especially in young adults.
PMID- 28420998
TI - Instant Biofeedback Provided by Wearable Sensor Technology Can Help to Optimize
Exercise and Prevent Injury and Overuse.
PMID- 28420997
TI - MicroRNAs in Palatogenesis and Cleft Palate.
AB - Palatogenesis requires a precise spatiotemporal regulation of gene expression,
which is controlled by an intricate network of transcription factors and their
corresponding DNA motifs. Even minor perturbations of this network may cause
cleft palate, the most common congenital craniofacial defect in humans. MicroRNAs
(miRNAs), a class of small regulatory non-coding RNAs, have elicited strong
interest as key regulators of embryological development, and as etiological
factors in disease. MiRNAs function as post-transcriptional repressors of gene
expression and are therefore able to fine-tune gene regulatory networks. Several
miRNAs are already identified to be involved in congenital diseases. Recent
evidence from research in zebrafish and mice indicates that miRNAs are key
factors in both normal palatogenesis and cleft palate formation. Here, we provide
an overview of recently identified molecular mechanisms underlying palatogenesis
involving specific miRNAs, and discuss how dysregulation of these miRNAs may
result in cleft palate.
PMID- 28420999
TI - Functional High-Intensity Circuit Training Improves Body Composition, Peak Oxygen
Uptake, Strength, and Alters Certain Dimensions of Quality of Life in Overweight
Women.
AB - The effects of circuit-like functional high-intensity training (CircuitHIIT)
alone or in combination with high-volume low-intensity exercise (Circuitcombined)
on selected cardio-respiratory and metabolic parameters, body composition,
functional strength and the quality of life of overweight women were compared. In
this single-center, two-armed randomized, controlled study, overweight women
performed 9-weeks (3 sessions.wk-1) of either CircuitHIIT (n = 11), or
Circuitcombined (n = 8). Peak oxygen uptake and perception of physical pain were
increased to a greater extent (p < 0.05) by CircuitHIIT, whereas Circuitcombined
improved perception of general health more (p < 0.05). Both interventions lowered
body mass, body-mass-index, waist-to-hip ratio, fat mass, and enhanced fat-free
mass; decreased ratings of perceived exertion during submaximal treadmill
running; improved the numbers of push-ups, burpees, one-legged squats, and 30-s
skipping performed, as well as the height of counter-movement jumps; and improved
physical and social functioning, role of physical limitations, vitality, role of
emotional limitations, and mental health to a similar extent (all p < 0.05).
Either forms of these multi-stimulating, circuit-like, multiple-joint training
can be employed to improve body composition, selected variables of functional
strength, and certain dimensions of quality of life in overweight women. However,
CircuitHIIT improves peak oxygen uptake to a greater extent, but with more
perception of pain, whereas Circuitcombined results in better perception of
general health.
PMID- 28421000
TI - Photodynamic Physiology-Photonanomanipulations in Cellular Physiology with
Protein Photosensitizers.
AB - Singlet oxygen generated in a type II photodynamic action, due to its limited
lifetime (1 MUs) and reactive distance (<10 nm), could regulate live cell
function nanoscopically. The genetically-encoded protein photosensitizers
(engineered fluorescent proteins such as KillerRed, TagRFP, and flavin-binding
proteins such as miniSOG, Pp2FbFPL30M) could be expressed in a cell type- and/or
subcellular organelle-specific manner for targeted protein photo-oxidative
activation/desensitization. The newly emerged active illumination technique
provides an additional level of specificity. Typical examples of photodynamic
activation include permanent activation of G protein-coupled receptor CCK1 and
photodynamic activation of ionic channel TRPA1. Protein photosensitizers have
been used to photodynamically modulate major cellular functions (such as
neurotransmitter release and gene transcription) and animal behavior. Protein
photosensitizers are increasingly used in photon-driven nanomanipulation in cell
physiology research.
PMID- 28421001
TI - Defining the Balance between Regeneration and Pathological Ossification in
Skeletal Muscle Following Traumatic Injury.
AB - Heterotopic ossification (HO) is characterized by the formation of bone at
atypical sites. This type of ectopic bone formation is most prominent in skeletal
muscle, most frequently resulting as a consequence of physical trauma and
associated with aberrant tissue regeneration. The condition is debilitating,
reducing a patient's range of motion and potentially causing severe pathologies
resulting from nerve and vascular compression. Despite efforts to understand the
pathological processes governing HO, there remains a lack of consensus regarding
the micro-environmental conditions conducive to its formation, and attempting to
define the balance between muscle regeneration and pathological ossification
remains complex. The development of HO is thought to be related to a complex
interplay between factors released both locally and systemically in response to
trauma. It develops as skeletal muscle undergoes significant repair and
regeneration, and is likely to result from the misdirected differentiation of
endogenous or systemically derived progenitors in response to biochemical and/or
environmental cues. The process can be sequentially delineated by the presence of
inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis,
chondrogenesis and ossification. However, exactly how each of these stages
contributes to the formation of HO is at present not well understood. Our
previous review examined the cellular contribution to HO. Therefore, the
principal aim of this review will be to comprehensively outline changes in the
local tissue micro-environment following trauma, and identify how these changes
can alter the balance between skeletal muscle regeneration and ectopic
ossification. An understanding of the mechanisms governing this condition is
required for the development and advancement of HO prophylaxis and treatment, and
may even hold the key to unlocking novel methods for engineering hard tissues.
PMID- 28421003
TI - Acellular Gelatinous Material of Human Umbilical Cord Enhances Wound Healing: A
Candidate Remedy for Deficient Wound Healing.
AB - Impaired wound healing is a severe clinical challenge and research into finding
effective wound healing strategies is underway as there is no ideal treatment.
Gelatinous material from the umbilical cord called Wharton's jelly is a valuable
source of mesenchymal stem cells which have been shown to aid wound healing.
While the cellular component of Wharton's jelly has been the subject of extensive
research during the last few years, little is known about the de-cellularized
jelly material of the umbilical cord. This is important as they are native niche
of stem cells. We have isolated Wharton's jelly from umbilical cords and then
fractionated acellular gelatinous Wharton's jelly (AGWJ). Here, we show for the
first time that AGWJ enhances wound healing in vitro as well as in vivo for
wounds in a murine model. In vivo staining of the wounds revealed a smaller wound
length in the AGWJ treated wounds in comparison to control treatment by enhancing
cell migration and differentiation. AGWJ significantly enhanced fibroblast cell
migration in vitro. Aside from cell migration, AGWJ changed the cell morphology
of fibroblasts to a more elongated phenotype, characteristic of myofibroblasts,
confirmed by upregulation of alpha smooth muscle actin using immunoblotting. AGWJ
treatment of wounds led to accelerated differentiation of cells into
myofibroblasts, shortening the proliferation phase of wound healing. This data
provides support for a novel wound healing remedy using AGWJ. AGWJ being native
biological, cost effective and abundantly available globally, makes it a highly
promising treatment option for wound dressing and skin regeneration.
PMID- 28421002
TI - Application of Stem Cells in Oral Disease Therapy: Progresses and Perspectives.
AB - Stem cells are undifferentiated and pluripotent cells that can differentiate into
specialized cells with a more specific function. Stem cell therapies become
preferred methods for the treatment of multiple diseases. Oral and maxillofacial
defect is one kind of the diseases that could be most possibly cured by stem cell
therapies. Here we discussed oral diseases, oral adult stem cells, iPS cells, and
the progresses/challenges/perspectives of application of stem cells for oral
disease treatment.
PMID- 28421004
TI - Neurosensory and Cognitive Modifications in Europe's Toughest RandoRaid
Competition: the Transpyrenea Extreme Study.
AB - Introduction: Given the wide proliferation of ultra-long endurance races, it is
important to understand the physiological response of the athletes to improve
their safety. We evaluated the cognitive and neurosensory effects on ultra
endurance athletes during the Transpyrenea (866 Km, 65,000 m positive slope),
held on the French Pyrenees. Materials and Methods: 40 athletes were enrolled
(age 43.8 +/- 8.8 years; 36 males). Olfactory and cognitive tests were performed
before the race (T0, n = 40), at 166 kms (T1, n = 28), at 418 kms (T2, n = 20),
and after the race (T3, 866 kms, n = 13). The effect of dehydration and sleep
deprivation on cognitive features were also studied. Results: Olfactory function
decreased during the race (T0: 24.9 +/- 4.3 vs. T3: 22.8 +/- 3.5, z = -2.678, p =
0.007), language fluency increased (T0: 10.8 +/- 2.9; T1: 11.4 +/- 2.7; T2: 12.9
+/- 2.8; T3: 12.9 +/- 3.0; chi2 = 11.132, p = 0.011 for combined samples),
whereas the Trail Making Test did not show any changes between pre- and post-race
(T0 vs. T3 p = 0.697 for TMT-A, p = 0.977 for TMT-B). The mean aggregate sleeping
time was 9.3 +/- 5.4 h at T1, 22.4 +/- 10.0 h at T2, 29.5 +/- 20.5 h at T3, with
a correlation with olfactory function (r = 0.644, p = 0.018), while Total Body
Water (TBW) was not correlated with olfactory or cognitive scores. Conclusion:
Physical activity and sleep restriction in ultra-endurance could transiently
affect olfactory function, while verbal fluency improved, demonstrating a
dissimilar mechanism of activation/deactivation in different cortical areas. Body
water loss was uncorrelated to cognition. Further studies should clarify whether
cognitive and sensory deficits occur even in absence of sleep restriction.
PMID- 28421006
TI - Do Demographic Characteristics Make Differences? Demographic Characteristics as
Moderators in the Associations between Only Child Status and Cognitive/Non
cognitive Outcomes in China.
AB - Different family compositions and sizes may affect child development through the
different modes of interaction between family members. Previous studies have
compared only children with non-only children in cognitive/non-cognitive
outcomes. However, relatively little research has systematically investigated the
potential moderators among them. Using a large and representative sample of
Chinese students (Grades 7-8; N = 5,752), this study examines the roles of
demographic characteristics, such as gender, region, parental educational level,
parental expectations, family socio-economic status and family structure, in the
associations between only child status and cognitive/non-cognitive outcomes. For
the cognitive outcomes, only child status exerts an influence on the students'
academic performance in Chinese and mathematics in the sample of three districts'
students. The examined associations between only child status and cognitive
outcomes are different in region, parental education, parental expectations and
family structure, while gender and family socio-economic status did not. For the
non-cognitive outcomes, only child status exerts an influence on the students'
school well-being, academic self-efficacy, academic self-concept, and internal
academic motivation in the full sample of students, but not on external academic
motivation. Further, the examined associations between only child status and non
cognitive outcomes are different in region, parental education, family socio
economic status and family structure, while gender and parental expectations did
not. These findings suggest that the associations between only child status and
cognitive/non-cognitive outcomes are heterogeneous in terms of some of the
demographic characteristics. Possible explanations are proposed in some concepts
of region and family environment in China.
PMID- 28421007
TI - Arousal Rules: An Empirical Investigation into the Aesthetic Experience of Cross
Modal Perception with Emotional Visual Music.
AB - Emotional visual music is a promising tool for the study of aesthetic perception
in human psychology; however, the production of such stimuli and the mechanisms
of auditory-visual emotion perception remain poorly understood. In Experiment 1,
we suggested a literature-based, directive approach to emotional visual music
design, and inspected the emotional meanings thereof using the self-rated
psychometric and electroencephalographic (EEG) responses of the viewers. A two
dimensional (2D) approach to the assessment of emotion (the valence-arousal
plane) with frontal alpha power asymmetry EEG (as a proposed index of valence)
validated our visual music as an emotional stimulus. In Experiment 2, we used our
synthetic stimuli to investigate possible underlying mechanisms of affective
evaluation mechanisms in relation to audio and visual integration conditions
between modalities (namely congruent, complementation, or incongruent
combinations). In this experiment, we found that, when arousal information
between auditory and visual modalities was contradictory [for example, active (+)
on the audio channel but passive (-) on the video channel], the perceived emotion
of cross-modal perception (visual music) followed the channel conveying the
stronger arousal. Moreover, we found that an enhancement effect (heightened and
compacted in subjects' emotional responses) in the aesthetic perception of visual
music might occur when the two channels contained contradictory arousal
information and positive congruency in valence and texture/control. To the best
of our knowledge, this work is the first to propose a literature-based directive
production of emotional visual music prototypes and the validations thereof for
the study of cross-modally evoked aesthetic experiences in human subjects.
PMID- 28421008
TI - Understanding Rejection between First-and-Second-Grade Elementary Students
through Reasons Expressed by Rejecters.
AB - Objective: The aim of this research was to obtain the views of young children
regarding their reasons for rejecting a peer. Method: To achieve this goal, we
conducted a qualitative study in the context of theory building research using an
analysis methodology based on Grounded Theory. The collected information was
extracted through semi-structured individual interviews from a sample of 853
children aged 6 from 13 urban public schools in Spain. Results: The children
provided 3,009 rejection nominations and 2,934 reasons for disliking the rejected
peers. Seven reason categories emerged from the analysis. Four categories refer
to behaviors of the rejected children that have a cost for individual peers or
peer group such as: direct aggression, disturbance of wellbeing, problematic
social and school behaviors and dominance behaviors. A further two categories
refer to the identities arising from the preferences and choices of rejected and
rejecter children and their peers: personal identity expressed through
preferences and disliking, and social identity expressed through outgroup
prejudices. The "no-behavior or no-choice" reasons were covered by one category,
unfamiliarity. In addition, three context categories were found indicating the
participants (interpersonal-group), the impact (low-high), and the subjectivity
(subjective-objective) of the reason. Conclusion: This study provides researchers
and practitioners with a comprehensive taxonomy of reasons for rejection that
contributes to enrich the theoretical knowledge and improve interventions for
preventing and reducing peer rejection.
PMID- 28421005
TI - Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases: A Template for
Innovative Therapy.
AB - Neurodegenerative and psychiatric diseases (NPDs) are today's most important
group of diseases, surpassing both atherosclerotic cardiovascular disease and
cancer in morbidity incidence. Although NPDs have a dramatic impact on our
society because of their high incidence, mortality, and severe debilitating
character, remarkably few effective interventions have become available. The
current treatments, if available, comprise the lifelong intake of general
immunosuppressants to delay disease progression or neurotransmitter
antagonists/agonists to dampen undesired behaviors. The long-term usage of such
medication, however, coincides with often severe adverse side effects. There is,
therefore, an urgent need for safe and effective treatments for these diseases.
Here, we discuss that many NPDs coincide with subtle chronic or flaring brain
inflammation sometimes escalating with infiltrations of lymphocytes in the
inflamed brain parts causing mild to severe or even lethal brain damage. Thus,
NPDs show all features of autoimmune diseases. In this review, we postulate that
NPDs resemble autoimmune-driven inflammatory diseases in many aspects and may
belong to the same disease spectrum. Just like in autoimmune diseases, NPD
symptoms basically are manifestations of a chronic self-sustaining inflammatory
process with detrimental consequences for the patient. Specific inhibition of the
destructive immune responses in the brain, leaving the patient's immune system
intact, would be the ultimate solution to cure patients from the disease. To
reach this goal, the primary targets, e.g., the primary self-antigens (pSAgs) of
the patient's chronic (auto)immune response, need to be identified. For a few
major NPDs, immunological studies led to the identification of the pSAgs involved
in the autoimmune damage of specific brain parts. However, further research is
needed to complete the list of pSAgs for all NPDs. Such immunological studies
will not only provide crucial insights into NPD pathogenesis but also ultimately
enable the development of a new generation of safe and effective immunotherapies
for NPDs. Interventions that will dramatically improve the life expectancy and
quality of life of individual patients and, moreover, will significantly reduce
the health-care costs of the society in general.
PMID- 28421011
TI - Practical Consequences of Item Response Theory Model Misfit in the Context of
Test Equating with Mixed-Format Test Data.
AB - In item response theory (IRT) models, assessing model-data fit is an essential
step in IRT calibration. While no general agreement has ever been reached on the
best methods or approaches to use for detecting misfit, perhaps the more
important comment based upon the research findings is that rarely does the
research evaluate IRT misfit by focusing on the practical consequences of misfit.
The study investigated the practical consequences of IRT model misfit in
examining the equating performance and the classification of examinees into
performance categories in a simulation study that mimics a typical large-scale
statewide assessment program with mixed-format test data. The simulation study
was implemented by varying three factors, including choice of IRT model, amount
of growth/change of examinees' abilities between two adjacent administration
years, and choice of IRT scaling methods. Findings indicated that the extent of
significant consequences of model misfit varied over the choice of model and IRT
scaling methods. In comparison with mean/sigma (MS) and Stocking and Lord
characteristic curve (SL) methods, separate calibration with linking and fixed
common item parameter (FCIP) procedure was more sensitive to model misfit and
more robust against various amounts of ability shifts between two adjacent
administrations regardless of model fit. SL was generally the least sensitive to
model misfit in recovering equating conversion and MS was the least robust
against ability shifts in recovering the equating conversion when a substantial
degree of misfit was present. The key messages from the study are that practical
ways are available to study model fit, and, model fit or misfit can have
consequences that should be considered when choosing an IRT model. Not only does
the study address the consequences of IRT model misfit, but also it is our hope
to help researchers and practitioners find practical ways to study model fit and
to investigate the validity of particular IRT models for achieving a specified
purpose, to assure that the successful use of the IRT models are realized, and to
improve the applications of IRT models with educational and psychological test
data.
PMID- 28421010
TI - Teacher Evaluations of Executive Functioning in Schoolchildren Aged 9-12 and the
Influence of Age, Sex, Level of Parental Education.
AB - Executive functions (EFs) develop over the period of early childhood and
adolescence up until young adulthood. Individual children differ substantially in
the pace at which their EFs develop, and characteristics such as sex and the
level of parental education (LPE) are thought to contribute to these differences.
In the present study, we assessed age-related changes in EFs as perceived and
evaluated by teachers and parents as well as the influence of sex and LPE on
their evaluations. We used a newly developed observer-report questionnaire, the
Amsterdam Executive Function Inventory (AEFI). The AEFI assesses three important
components of the executive aspects of daily life behavior in 13 questions:
Attention; Self-control and Self-monitoring; and Planning and Initiative taking.
Teachers and parents evaluated these aspects of executive functioning in 186
schoolchildren in grades 3-6 (age: 9-12 years). Age effects within grades and
differences in social economic status between the four participating schools were
controlled. Results showed a significant increase in teacher-perceived EFs from
third to fourth grades and from fifth to sixth grades. This development was
influenced both by the sex of the child and by the LPE. As perceived by teachers,
the component self-control and self-monitoring was higher for girls than for
boys, and planning abilities were higher for children from families with a higher
LPE. Additional analyses showed that there is a systematic and statistically
significant difference between the evaluations of the teachers and that of
parents. Parents reported higher scores for planning, whereas teachers reported
higher scores for self-control and self-monitoring. Evaluations by parents and
teachers were different for girls, but not for boys. These findings are important
because they imply that the development of EFs as perceived by parents and
teachers is influenced by child-related factors. Second, there are clear
differences in evaluations between teachers and parents. The AEFI appears to be a
tool that is easily used by parents and teachers and shows potential for
monitoring the development of EFs as perceived by significant others during young
adolescence.
PMID- 28421009
TI - Food Addiction in Gambling Disorder: Frequency and Clinical Outcomes.
AB - Background: The food addiction (FA) model is receiving increasing interest from
the scientific community. Available empirical evidence suggests that this
condition may play an important role in the development and course of physical
and mental health conditions such as obesity, eating disorders, and other
addictive behaviors. However, no epidemiological data exist on the comorbidity of
FA and gambling disorder (GD), or on the phenotype for the co-occurrence of
GD+FA. Objectives: To determine the frequency of the comorbid condition GD+FA, to
assess whether this comorbidity features a unique clinical profile compared to GD
without FA, and to generate predictive models for the presence of FA in a GD
sample. Method: Data correspond to N = 458 treatment-seeking patients who met
criteria for GD in a hospital unit specialized in behavioral addictions. Results:
Point prevalence for FA diagnosis was 9.2%. A higher ratio of FA was found in
women (30.5%) compared to men (6.0%). Lower FA prevalence was associated with
older age. Patients with high FA scores were characterized by worse psychological
state, and the risk of a FA diagnosis was increased in patients with high scores
in the personality traits harm avoidance and self-transcendence, and low scores
in cooperativeness (R2 = 0.18). Conclusion: The co-occurrence of FA in treatment
seeking GD patients is related to poorer emotional and psychological states. GD
treatment interventions and related behavioral addictions should consider
potential associations with problematic eating behavior and aim to include
techniques that aid patients in better managing this behavior.
PMID- 28421012
TI - Moderated Online Social Therapy: A Model for Reducing Stress in Carers of Young
People Diagnosed with Mental Health Disorders.
AB - Family members caring for a young person diagnosed with the onset of mental
health problems face heightened stress, depression, and social isolation. Despite
evidence for the effectiveness of family based interventions, sustaining access
to specialist family interventions is a major challenge. The availability of the
Internet provides possibilities to expand and sustain access to evidence-based
psychoeducation and personal support for family members. In this paper we
describe the therapeutic model and the components of our purpose-built moderated
online social therapy (MOST) program for families. We outline the background to
its development, beginning with our face-to-face EPISODE II family intervention,
which informed our selection of therapeutic content, and the integration of
recent developments in positive psychology. Our online interventions for carers
integrate online therapy, online social networking, peer and expert support, and
online social problem solving which has been designed to reduce stress in carers.
The initial version of our application entitled Meridian was shown to be safe,
acceptable, and feasible in a feasibility study of carers of youth diagnosed with
depression and anxiety. There was a significant reduction in self-reported levels
of stress in caregivers and change in stress was significantly correlated with
use of the system. We have subsequently launched a cluster RCT for caregivers
with a relative diagnosed with first-episode psychosis. Our intervention has the
potential to improve access to effective specialist support for families facing
the onset of serious mental health problems in their young relative.
PMID- 28421014
TI - Group Rumination: Social Interactions Around Music in People with Depression.
AB - One of the most important roles that music serves in human society is the
promotion of social relationships and group cohesion. In general, emotional
experiences tend to be amplified in group settings through processes of social
feedback. However, previous research has established that listening to sad music
can intensify negative emotions in people with tendencies to rumination and
depression. This study therefore investigated the phenomenon of ruminating with
music, and the question of whether listening to sad music in group settings
provides social benefits for emotionally vulnerable listeners, or whether it
further exaggerates depressive tendencies. Participants recruited via online
depression groups and mental health websites were surveyed as to music listening
habits. Results revealed that people with depression were more likely to engage
in "group rumination" using music, and that this behavior could be partially
explained by a general tendency to ruminate using music. Both affective states
and coping styles were found to be related to the affective outcomes of group
interactions around music. These findings go some way toward clarifying the
situations in which group interactions around music are able to provide important
social benefits for those involved, and situations in which negative emotions can
be amplified by the group context.
PMID- 28421013
TI - The Blurred Future of Adolescent Gamblers: Impulsivity, Time Horizon, and
Emotional Distress.
AB - The main purpose of this study was to investigate the interplay of functional and
dysfunctional impulsivity, delay discounting, time perspective, and emotional
negative states on gambling severity in Italian adolescents. A second aim of the
study was to analyze the developmental trajectories of gambling involvement,
functional and dysfunctional impulsivity, delay discounting, consideration of
future consequences, and negative affectivity in a cross-sectional perspective.
One thousand and ten Italian adolescents aging between 12 and 19 years were
administered the South Oaks Gambling Screen Revised for Adolescents (SOGS-RA),
the Functional and Dysfunctional Impulsivity Scale (FDIS), the Monetary Choice
Questionnaire (MCQ), the Consideration of Future Consequences Scale (CFC-14), and
the Depression, Anxiety and Stress Scales-21 (DASS-21). Data analyses were
conducted using correlational analysis, Chi-square test, analysis of variance,
and hierarchical regression analysis. Results indicated that, relative to non
gamblers and non-problem gamblers, at-risk and problem gamblers showed higher
levels of impulsivity, steeper delay discounting, shorter time horizon, and
reported experiencing significantly higher levels of depression, anxiety, and
stress. Results of hierarchical regression analysis, with SOGS-RA scores as the
dependent variable, and gender, age, FDIS, MCQ, CFC-14, and DASS-21 scores as
independent variables, indicated that, along with gender and age, low scores of
future orientation and high scores of dysfunctional impulsivity, depression,
anxiety, present orientation, and delay discounting significantly predicted
gambling severity. These findings provide further evidence that the higher the
gambling involvement, the greater the tendency to devalue delayed rewards and to
focus on the immediate consequences of one's behavior. Interestingly, for the
first time these results reveal an association between gambling severity and both
dysfunctional impulsivity and negative affective states across adolescence.
Finally, results of cross-sectional analyses suggest that gambling severity
contributes more than age in shaping the developmental trajectories of functional
and dysfunctional impulsivity, delay discounting, time perspective, and negative
affective states.
PMID- 28421015
TI - Music and Its Inductive Power: A Psychobiological and Evolutionary Approach to
Musical Emotions.
AB - The aim of this contribution is to broaden the concept of musical meaning from an
abstract and emotionally neutral cognitive representation to an emotion
integrating description that is related to the evolutionary approach to music.
Starting from the dispositional machinery for dealing with music as a temporal
and sounding phenomenon, musical emotions are considered as adaptive responses to
be aroused in human beings as the product of neural structures that are
specialized for their processing. A theoretical and empirical background is
provided in order to bring together the findings of music and emotion studies and
the evolutionary approach to musical meaning. The theoretical grounding
elaborates on the transition from referential to affective semantics, the
distinction between expression and induction of emotions, and the tension between
discrete-digital and analog-continuous processing of the sounds. The empirical
background provides evidence from several findings such as infant-directed
speech, referential emotive vocalizations and separation calls in lower mammals,
the distinction between the acoustic and vehicle mode of sound perception, and
the bodily and physiological reactions to the sounds. It is argued, finally, that
early affective processing reflects the way emotions make our bodies feel, which
in turn reflects on the emotions expressed and decoded. As such there is a
dynamic tension between nature and nurture, which is reflected in the nature
nurture-nature cycle of musical sense-making.
PMID- 28421016
TI - Online Coaching of Emotion-Regulation Strategies for Parents: Efficacy of the
Online Rational Positive Parenting Program and Attention Bias Modification
Procedures.
AB - Parenting programs are currently treatment of choice for behavioral disorders in
children and one of their main components is reducing the negativity bias in the
child-parent dyad. The Rational Positive Parenting Program (rPPP) is a program
with a special focus on parent emotion-regulation functional reappraisal
strategies, which has recently received consistent support for reducing child
externalizing and internalizing disorders. In the last years, online
interventions were proliferated and the Attention Bias Modification (ABM)
becoming a promising implicit therapeutic intervention based on attention
deployment emotion-regulation strategy, or adjunctive module to usual treatments,
with results in multiple domains, varying from pain to self-esteem and emotional
disorders (e.g., anxiety). We conducted two studies to investigate (1) the
efficacy of the ABM procedures applied to parents and (2) the efficacy of the
online version of the rPPP augmented with an ABM module. A total of 42 parents of
children aged 2-12 years old participated in the first study, being allocated
either to the ABM training or wait-list. Positive results were reported by the
parents participating in the ABM group for own distress, satisfaction, positive
interactions with the child, and child's strengths. In the second study, 53
parents and their children were allocated either in the rPPP group or in the rPPP
+ ABM group. Results show that ABM training can boost the effects of the rPPP on
the strengths of children reported by the parents after the intervention.
Findings are discussed in the light of limited research on using online tools for
coaching effective emotion-regulation strategies for parents.
PMID- 28421018
TI - The Emergence of Explicit Knowledge in a Serial Reaction Time Task: The Role of
Experienced Fluency and Strength of Representation.
AB - The Serial Reaction Time Task (SRTT) is an important paradigm to study the
properties of unconscious learning processes. One specifically interesting and
still controversially discussed topic are the conditions under which
unconsciously acquired knowledge becomes conscious knowledge. The different
assumptions about the underlying mechanisms can contrastively be separated into
two accounts: single system views in which the strengthening of associative
weights throughout training gradually turns implicit knowledge into explicit
knowledge, and dual system views in which implicit knowledge itself does not
become conscious. Rather, it requires a second process which detects changes in
performance and is able to acquire conscious knowledge. In a series of three
experiments, we manipulated the arrangement of sequential and deviant trials. In
an SRTT training, participants either received mini-blocks of sequential trials
followed by mini-blocks of deviant trials (22 trials each) or they received
sequential and deviant trials mixed randomly. Importantly the number of correct
and deviant transitions was the same for both conditions. Experiment 1 showed
that both conditions acquired a comparable amount of implicit knowledge,
expressed in different test tasks. Experiment 2 further demonstrated that both
conditions differed in their subjectively experienced fluency of the task, with
more fluency experienced when trained with mini-blocks. Lastly, Experiment 3
revealed that the participants trained with longer mini-blocks of sequential and
deviant material developed more explicit knowledge. Results are discussed
regarding their compatibility with different assumptions about the emergence of
explicit knowledge in an implicit learning situation, especially with respect to
the role of metacognitive judgements and more specifically the Unexpected-Event
Hypothesis.
PMID- 28421017
TI - Review on Neural Correlates of Emotion Regulation and Music: Implications for
Emotion Dysregulation.
AB - Previous studies have examined the neural correlates of emotion regulation and
the neural changes that are evoked by music exposure. However, the link between
music and emotion regulation is poorly understood. The objectives of this review
are to (1) synthesize what is known about the neural correlates of emotion
regulation and music-evoked emotions, and (2) consider the possibility of
therapeutic effects of music on emotion dysregulation. Music-evoked emotions can
modulate activities in both cortical and subcortical systems, and across cortical
subcortical networks. Functions within these networks are integral to generation
and regulation of emotions. Since dysfunction in these networks are observed in
numerous psychiatric disorders, a better understanding of neural correlates of
music exposure may lead to more systematic and effective use of music therapy in
emotion dysregulation.
PMID- 28421019
TI - Gender Moderates the Influence of Self-Construal Priming on Fairness
Considerations.
AB - Research in social and cultural psychology has identified that self-construal, or
the way the self is defined in relation to others, plays an important role in
social decision-making processes. Yet it remains difficult to isolate the effect
of self-construal in a comparative approach. Therefore, we used priming
methodology in three studies to induce either an independent or interdependent
mindset to test direct consequences on fairness considerations. Specifically, we
asked whether participants would accept an unfair ultimatum game offer: a split
of 10 euros, where the participant is allocated the marginal share of 3 and the
proposer 7. If the participant refuses, neither gets paid. In the first study, we
used the well-known similarities and differences prime. Here, activating an
interdependent mindset decreased rejection of the unfair offer compared to the
independent mindset and control condition, but only in females. The prime did not
affect males. In the second and third study we modified our university's mission
statement to instead include either independent or interdependent values. Females
displayed a similar direction of effects; in males however, activating an
interdependent mindset increased rejection. Taken together, the results show that
whether participants accept or reject an unfair offer depends on both their
gender and the self-construal prime. The results were interpreted using the
distinction between relational independence that has been associated with
females, and collective interdependence, that has been associated with males.
Possible consequences for future studies are discussed.
PMID- 28421020
TI - Social Dominance Orientation, Dispositional Empathy, and Need for Cognitive
Closure Moderate the Impact of Empathy-Skills Training, but Not Patient Contact,
on Medical Students' Negative Attitudes toward Higher-Weight Patients.
AB - Anti-fat bias in healthcare providers and medical students has serious
implications for quality of care of higher-weight patients. Studies of
interventions aimed at reducing anti-fat attitudes in medical students have
generally been disappointing, with little enduring effect. It is possible that
some students may be more receptive to prejudice-reducing influences than others,
due to underlying differences in their personal characteristics. It is also
possible that attitudes toward patients, specifically, may differ from anti-fat
attitudes in general, and prejudice-reduction effectiveness on patient-specific
attitudes has not yet been evaluated. The present study explored the effect on
general and patient-specific anti-fat attitudes of (1) contact with higher-weight
individuals prior to and during medical school; and (2) training designed to
increase medical students' empathy toward patients by encouraging them to take
the patient's perspective during clinical encounters. The moderating role of
individual difference factors on effectiveness of contact and student-reported
hours of empathy training on patient-specific attitudes was assessed. A total of
3,576 students enrolled across 49 US medical schools completed an online survey
at the start of their first year of medical school and at the end of their fourth
year. Favorable contact experience with higher-weight patients predicted improved
attitudes toward heavier patients after 4 years of medical school, and appeared
sufficient to partially offset the effects of dislike of higher-weight
individuals at baseline. The impact of favorable contact on general anti-fat
attitudes was less strong, highlighting the importance of using target-specific
outcome measures. The positive effects of favorable contact on attitudes toward
higher-weight patients did not differ based on students' baseline levels of
social dominance orientation, dispositional empathy, or need for cognitive
closure. In contrast, the effectiveness of training did vary by student
characteristics, generally being more effective in students who were more
egalitarian and empathic at baseline, with little effect, or even adverse effects
in students low in these traits. Overall, however, perspective-taking training
produced only small improvements in attitudes toward higher-weight patients.
PMID- 28421021
TI - Employee Wellbeing: Evaluating a Wellbeing Intervention in Two Settings.
AB - This research presents two studies conducted to evaluate the Wellbeing Game in
two different contexts: In a student sample and in an organizational setting.
Study 1 investigated the efficacy of the Wellbeing Game, in terms of its effect
of wellbeing, stress, and an image valence test, among 60 university students.
The results showed that after playing the Wellbeing Game, students reported a
significant positive change in wellbeing compared to those who did not play the
Wellbeing Game, but there was no decrease in stress or any change in
classification of image valence. Study 2 evaluated the Wellbeing Game in an
organizational context. Employees (n = 52) in a financial organization played the
Wellbeing Game for 4 weeks and answered survey questions about wellbeing and
stress at the beginning and end of this period. The results showed that after
playing the Wellbeing Game, employees reported lower stress levels, and higher
wellbeing levels for those who felt that it had helped them connect more with
colleagues. The results from the two studies provide preliminary support that the
Wellbeing Game may be an effective wellbeing intervention tool in both an
organization and a non-organizational context.
PMID- 28421022
TI - Commentary: How to Make the Ghosts in my Bedroom Disappear? Focused-Attention
Meditation Combined with Muscle Relaxation (MR Therapy)-A Direct Treatment
Intervention for Sleep Paralysis.
PMID- 28421023
TI - Editorial: Phonology in the Bilingual and Bidialectal Lexicon.
PMID- 28421024
TI - Family and Individual Risk and Protective Factors of Depression among Chinese
Migrant Children with Oppositional Defiant Disorder Symptoms.
AB - Migrant children reached 35.81 million in China and were vulnerable to serious
emotional problems including depression. The present study aimed to identify the
family and individual risk and protective factors for depression in an at-risk
sample of Chinese migrant children. Participants were 368 children (9.47 +/- 1.46
years old, 73.4% boys) who had at least one symptom of Oppositional Defiant
Disorder symptoms (ODD) and their parents in Mainland China. Risk and protective
factors within both family (i.e., family maltreatment and family functioning) and
individual (i.e., automatic thoughts and resilience) perspectives. Family
maltreatment and negative automatic thoughts served as risk factors in relation
to children's depression. Further, automatic thoughts mediated the relationship
between family maltreatment and children's depression. Family functioning
(cohesion, but bot adaptability) and individual resilience could buffer the
effects of risk factors in the Structure Emotion Model such that both cohesion
and resilience moderated the relationship between family maltreatment and
children's automatic thoughts only. Our findings highlighted the urgent need to
decrease risk factors and increase protective factors of both family and child
individual characteristics in prevention and intervention depression among
migrant children with ODD symptoms in China.
PMID- 28421025
TI - The Use of Lausanne Trilogue Play in Three Cases of Gastroschisis Diagnosed
during Pregnancy.
AB - From pregnancy to the 1st years of a child's life, families develop and increase
representations and interactive competences toward the child. Prenatal diagnosis
of a severe fetus' defect could profoundly alter the parental perception and
development of these representations. The aim of the study was to evaluate
triadic interactions in families, whose baby was prenatally diagnosed with severe
gastroschisis. Three families took part in the preliminary case study, which was
carried out when the babies were 6 months old. The Lausanne Trilogue Play shows
that prenatal diagnosis of fetal malformation may affect family triadic
interactions as follows: (a) parents, especially mothers, tend to be intrusive
during the play; (b) parents presents maladjustments in the child stimulations,
especially during the third part, when both parents have to simultaneously
interact with the baby; (c) parents experience difficulties in creating a space
that allows them to communicate directly with each other, leaving the child in a
peripheral position. Observational data and clinical implications are discussed.
PMID- 28421026
TI - Keeping the Spirits Up: The Effect of Teachers' and Parents' Emotional Support on
Children's Working Memory Performance.
AB - Working memory, used to temporarily store and mentally manipulate information, is
important for children's learning. It is therefore valuable to understand which
(contextual) factors promote or hinder working memory performance. Recent
research shows positive associations between positive parent-child and teacher
student interactions and working memory performance and development. However, no
study has yet experimentally investigated how parents and teachers affect working
memory performance. Based on attachment theory, the current study investigated
the role of parent and teacher emotional support in promoting working memory
performance by buffering the negative effect of social stress. Questionnaires and
an experimental session were completed by 170 children from grade 1 to 2 (Mage =
7 years 6 months, SD = 7 months). Questionnaires were used to assess children's
perceptions of the teacher-student and parent-child relationship. During an
experimental session, working memory was measured with the Corsi task backward
(Milner, 1971) in a pre- and post-test design. In-between the tests stress was
induced in the children using the Cyberball paradigm (Williams et al., 2000).
Emotional support was manipulated (between-subjects) through an audio message
(either a weather report, a supportive message of a stranger, a supportive
message of a parent, or a supportive message of a teacher). Results of repeated
measures ANOVA showed no clear effect of the stress induction. Nevertheless, an
effect of parent and teacher support was found and depended on the quality of the
parent-child relationship. When children had a positive relationship with their
parent, support of parents and teachers had little effect on working memory
performance. When children had a negative relationship with their parent, a
supportive message of that parent decreased working memory performance, while a
supportive message from the teacher increased performance. In sum, the current
study suggests that parents and teachers can support working memory performance
by being supportive for the child. Teacher support is most effective when the
child has a negative relationship with the parent. These insights can give
direction to specific measures aimed at preventing and resolving working memory
problems and related issues.
PMID- 28421027
TI - Universal Visual Features Might Be Necessary for Fluent Reading. A Longitudinal
Study of Visual Reading in Braille and Cyrillic Alphabets.
AB - It has been hypothesized that efficient reading is possible because all reading
scripts have been matched, through cultural evolution, to the natural
capabilities of the visual cortex. This matching has resulted in all scripts
being made of line-junctions, such as T, X, or L. Our aim was to test a critical
prediction of this hypothesis: visual reading in an atypical script that is
devoid of line-junctions (such as the Braille alphabet read visually) should be
much less efficient than reading in a "normal" script (e.g., Cyrillic). Using a
lexical decision task, we examined Visual Braille reading speed and efficiency in
sighted Braille teachers. As a control, we tested learners of a natural visual
script, Cyrillic. Both groups participated in a two semester course of either
visual Braille or Russian while their reading speed and accuracy was tested at
regular intervals. The results show that visual Braille reading is slow, prone to
errors and highly serial, even in Braille readers with years of prior reading
experience. Although subjects showed some improvements in their visual Braille
reading accuracy and speed following the course, the effect of word length on
reading speed (typically observed in beginning readers) was remained very
sizeable through all testing sessions. These results are in stark contrast to
Cyrillic, a natural script, where only 3 months of learning were sufficient to
achieve relative proficiency. Taken together, these results suggest that visual
features such as line junctions and their combinations might be necessary for
efficient reading.
PMID- 28421028
TI - Adult-Onset Niemann-Pick Disease Type C: Rapid Treatment Initiation Advised but
Early Diagnosis Remains Difficult.
AB - Niemann-Pick type C disease (NP-C) presents with heterogeneous neurological and
psychiatric symptoms. Adult onset is rare and possibly underdiagnosed due to
frequent lack of specific and obvious key symptoms. For both early and
adolescent/adult onset, the available data from studies and case reports describe
a positive effect of Miglustat (symptom relief or stabilization). However, due to
the low frequency of NP-C, experience with this therapy is still limited. We
describe two adult-onset cases of NP-C. In both cases, vertical supranuclear gaze
palsy was not recognized at symptom onset. Correct diagnosis was delayed from
onset of symptoms by more than 10 years. The video demonstrates the broad
spectrum of symptoms in later stages of the disease. Compared with published
data, the treatment outcome observed in our cases after delayed initiation of
Miglustat therapy was disappointing, with continuing disease progression in both
cases. Thus, early treatment initiation could be necessary to achieve a good
symptomatic effect. Hence, early biochemical testing for NP-C should be
considered in patients suffering from atypical neurological/neuropsychological
and psychiatric symptoms, even in cases of uncertainty.
PMID- 28421029
TI - A Historical View of Motion Sickness-A Plague at Sea and on Land, Also with
Military Impact.
AB - Seasickness and its triggers, symptoms, and preventive measures were well known
in antiquity. This chapter is based on an analysis of descriptions of motion
sickness, in particular seasickness, in ancient Greek, Roman, and Chinese
literature. A systematic search was made from the Greek period beginning with
Homer in 800 BC to the late Roman period and ending with Aetios Amidenos in 600
AD, as well as in the Chinese medical classics dating from around 300 AD. Major
aspects are the following: body movements caused by waves were identified in all
cultures as the critical stimuli. The ancient Greeks and Romans knew that other
illnesses and the mental state could precipitate seasickness and that experienced
sailors were highly resistant to it (habituation). The Chinese observed that
children were particularly susceptible to motion sickness; they first described
the type of motion sickness induced by traveling in carts (cart-sickness) or
being transported on a litter or in a sedan chair (litter-sickness). The western
classics recommended therapeutic measures like fasting or specific diets,
pleasant fragrancies, medicinal plants like white hellebore (containing various
alkaloids), or a mixture of wine and wormwood. The East knew more unusual
measures, such as drinking the urine of young boys, swallowing white sand-syrup,
collecting water drops from a bamboo stick, or hiding earth from the kitchen
hearth under the hair. The Greek view of the pathophysiology of seasickness was
based on the humoral theory of Empedokles and Aristoteles and differed from the
Chinese medicine of correspondences, which attributed malfunctions to certain
body substances and the life force Qi. Many sources emphasized the impact of
seasickness on military actions and famous naval battles such as the Battle of
the Red Cliff, which marked the end of the Han dynasty in China, or the defeat of
the Spanish Armada by the English in 1588. A peculiar form of motion sickness is
associated with Napoleon's camel corps during the Egyptian campaign of 1798/1799,
a sickness induced by riding on a camel. Thus, motion sickness in antiquity was
known as a physiological response to unadapted body motions during passive
transportation as well as a plague at sea.
PMID- 28421030
TI - Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.
AB - INTRODUCTION: In tinnitus treatment, there is a tendency to shift from a "one
size fits all" to a more individual, patient-tailored approach. Insight in the
heterogeneity of the tinnitus spectrum might improve the management of tinnitus
patients in terms of choice of treatment and identification of patients with
severe mental distress. The goal of this study was to identify subgroups in a
large group of tinnitus patients. METHODS: Data were collected from patients with
severe tinnitus complaints visiting our tertiary referral tinnitus care group at
the University Medical Center Groningen. Patient-reported and physician-reported
variables were collected during their visit to our clinic. Cluster analyses were
used to characterize subgroups. For the selection of the right variables to enter
in the cluster analysis, two approaches were used: (1) variable reduction with
principle component analysis and (2) variable selection based on expert opinion.
RESULTS: Various variables of 1,783 tinnitus patients were included in the
analyses. Cluster analysis (1) included 976 patients and resulted in a four
cluster solution. The effect of external influences was the most discriminative
between the groups, or clusters, of patients. The "silhouette measure" of the
cluster outcome was low (0.2), indicating a "no substantial" cluster structure.
Cluster analysis (2) included 761 patients and resulted in a three-cluster
solution, comparable to the first analysis. Again, a "no substantial" cluster
structure was found (0.2). CONCLUSION: Two cluster analyses on a large database
of tinnitus patients revealed that clusters of patients are mostly formed by a
different response of external influences on their disease. However, both cluster
outcomes based on this dataset showed a poor stability, suggesting that our
tinnitus population comprises a continuum rather than a number of clearly defined
subgroups.
PMID- 28421031
TI - Fatal Outcome of European Tick-borne Encephalitis after Vaccine Failure.
AB - Tick-borne encephalitis is a viral disease affecting the central nervous system.
It is endemic in Switzerland with 200-250 notified cases annually. Active
immunization is effective for persons in all age groups. Vaccine failure is rare,
in particular after a completed vaccination course. Here, we describe the case of
67-year-old man with a fatal outcome despite vaccination. The diagnosis was
confirmed by extensive postmortem analyses. The diagnostic challenges of vaccine
failure in tick-borne encephalitis and the dynamics of the immune response in
vaccination breakthrough are discussed.
PMID- 28421033
TI - Orthostatic Hypotension Predicts Cognitive Impairment in the Elderly: Findings
from a Cohort Study.
AB - BACKGROUND: Orthostatic hypotension (OH) is a known risk factor for cerebral
ischemia, but its correlation with cognitive impairment (CI) is not well
established. OBJECTIVE: The aim of this study is to explore the relationship
between OH and CI in the elderly. METHODS: The study group consisted of 44 OH
patients who presented with drowsiness, vertigo, and fatigue between January 2009
and December 2011 (OH group). Eighty-eight healthy elderly were paired with those
in the OH group in a 1:2 based on their education levels (NOH group). Baseline
sociodemographic information and cognition-related measures were collected for
both groups. Cognitive function was assessed 4 years later using MMSE. RESULTS:
The overall incidence of CI was 14.0% among the 114 subjects who completed the
follow-up assessment. There was a significant difference in the incidence of CI
between the OH group (23.7%) and the NOH group (9.2%) (chi2 = 4.399, P = 0.036).
After excluding the influence of age (OR = 1.199, 95% CI: 1.072-1.340, P = 0.001)
and education years (OR = 0.568, 95% CI: 0.371-0.869, P = 0.009), OH (OR = 4.047,
95% CI: 1.144-14.313, P = 0.030) became an independent risk factor for CI.
CONCLUSION: OH can lead to CI. We suggest that future studies, with a larger
sample size, use OH exposure time instead of OH exposure population to verify the
conclusion of this study.
PMID- 28421032
TI - Spasticity, Motor Recovery, and Neural Plasticity after Stroke.
AB - Spasticity and weakness (spastic paresis) are the primary motor impairments after
stroke and impose significant challenges for treatment and patient care.
Spasticity emerges and disappears in the course of complete motor recovery.
Spasticity and motor recovery are both related to neural plasticity after stroke.
However, the relation between the two remains poorly understood among clinicians
and researchers. Recovery of strength and motor function is mainly attributed to
cortical plastic reorganization in the early recovery phase, while reticulospinal
(RS) hyperexcitability as a result of maladaptive plasticity, is the most
plausible mechanism for poststroke spasticity. It is important to differentiate
and understand that motor recovery and spasticity have different underlying
mechanisms. Facilitation and modulation of neural plasticity through
rehabilitative strategies, such as early interventions with repetitive goal
oriented intensive therapy, appropriate non-invasive brain stimulation, and
pharmacological agents, are the keys to promote motor recovery. Individualized
rehabilitation protocols could be developed to utilize or avoid the maladaptive
plasticity, such as RS hyperexcitability, in the course of motor recovery.
Aggressive and appropriate spasticity management with botulinum toxin therapy is
an example of how to create a transient plastic state of the neuromotor system
that allows motor re-learning and recovery in chronic stages.
PMID- 28421034
TI - Is the Headache in Patients with Vestibular Migraine Attenuated by Vestibular
Rehabilitation?
AB - BACKGROUND: Vestibular rehabilitation is the most effective treatment for
dizziness due to vestibular dysfunction. Given the biological relationship
between vestibular symptoms and headache, headache in patients with vestibular
migraine (VM) could be improved by vestibular rehabilitation that leads to the
improvement of dizziness. This study aimed to compare the effects of vestibular
rehabilitation on headache and other outcomes relating to dizziness, and the
psychological factors in patients with VM patients, patients with dizziness and
tension-type headache, and patients without headache. METHODS: Our participants
included 251 patients with dizziness comprising 28 patients with VM, 79 patients
with tension-type headache, and 144 patients without headache. Participants were
hospitalized for 5 days and taught to conduct a vestibular rehabilitation
program. They were assessed using the Dizziness Handicap Inventory (DHI),
Headache Impact Test (HIT-6), Hospital Anxiety and Depression Scale (HADS), and
Somatosensory Catastrophizing Scale (SSCS) and underwent center of gravity
fluctuation measurement as an objective dizziness severity index before, 1 month
after, and 4 months after their hospitalization. RESULTS: The VM and tension-type
headache groups demonstrated a significant improvement in the HIT-6 score with
improvement of the DHI, HADS, SSCS, and a part of the objective dizziness index
that also shown in patients without headache following vestibular rehabilitation.
The change in HIT-6 during rehabilitation in the VM group was positively
correlated with changes in the DHI and anxiety in the HADS. Changes in the HIT-6
in tension-type headache group positively correlated with changes in anxiety and
SSCS. CONCLUSION: Vestibular rehabilitation contributed to improvement of
headache both in patients with VM and patients with dizziness and tension-type
headache, in addition to improvement of dizziness and psychological factors.
Improvement in dizziness following vestibular rehabilitation could be associated
with the improvement of headache more prominently in VM compared with comorbid
tension-type headache.
PMID- 28421035
TI - Antiepileptic Drugs Impair Shortening of Isolated Cardiomyocytes.
AB - BACKGROUND: Most antiepileptic drugs (AEDs) inhibit seizure generation by acting
on voltage-dependent ion channels. Voltage-dependent sodium and calcium channels
are commonly expressed in brain and heart, suggesting that AEDs may have
considerable cardiodepressive effects, thereby facilitating sudden cardiac death
as a potential cause of sudden unexpected death in epilepsy. Here, we
investigated the effects of carbamazepine (CBZ), lamotrigine (LTG), and
levetiracetam (LEV) alone and in combination on the shortening properties of
isolated ventricular cardiomyocytes of wild-type mice. METHODS: Properties of
murine cardiomyocytes were determined by recording the sarcomere shortening with
a video imaging system before, during, and after administration of AEDs in
different concentrations and combinations. We assessed (i) the number of
successful shortenings during continuous electrical stimulation
(electromechanical coupling) and (ii) the shortening amplitude as well as other
shortening-related properties upon repetitive electrical stimulation at 4 Hz.
Data are given as mean +/- SEM. RESULTS: At 100 MUM, CBZ (10 cells), LTG (11
cells), and LEV (11 cells) alone had no effect on the electromechanical coupling
but reversibly reduced shortening amplitudes by 15 +/- 4, 24 +/- 3, and 11 +/-
3%, respectively. Increasing the LTG concentration to 250 (21 cells) and 500 MUM
(4 cells) reversibly inhibited the electromechanical coupling in 62 and 100% of
the experiments. Importantly, simultaneous application of CBZ, LTG, and LEV at
100 MUM also impaired the electromechanical coupling in 8 of 19 cardiomyocytes
(42%) and reduced the shortening amplitude by 21 +/- 4%. CONCLUSION: Our data
show that AEDs reversibly impair cardiac excitation and contraction. Importantly,
the blocking effect on electromechanical coupling appears to be additive when
different AEDs are simultaneously applied. The translational value of these
experimental findings into clinical practice is limited. Our results, however,
suggest that rationale AED therapy may be important with respect to cardiac side
effects and potential facilitation of serious cardiac dysfunction especially when
AEDs are used in combination or at very high doses.
PMID- 28421036
TI - Genetics of Thyroid-Stimulating Hormone Receptor-Relevance for Autoimmune Thyroid
Disease.
AB - Production of thyroid-stimulating hormone receptor (TSHR) antibodies represents
the hallmark of Graves' disease (GD) pathogenesis. Thus, for more than two
decades the TSHR gene has been at the center of studies intended to elucidate its
contribution to disease pathology. The advent of genome-wide association
technology allowed to establish a strong association of the TSHR gene with GD.
Subsequent fine-mapping studies narrowed the disease-susceptibility region to a
40 kb sequence in intron 1, where at least five GD-associated SNPs in tight
linkage disequilibrium were identified. The current challenge is to understand
the functional mechanisms by which these polymorphisms modify physiological
processes and trigger disease. The aim of this review is to summarize the current
knowledge on the role of the TSHR gene in GD pathogenesis, which has been gained
through linkage and association studies, as well as to discuss the emerging
mechanisms underlying biological implications of TSHR variants in the development
of GD.
PMID- 28421038
TI - Bacteriophages against Serratia as Fish Spoilage Control Technology.
AB - Bacteria of the genus Serratia, mainly S. proteamaculans and S. fonticola, are
important spoilage agents in Atlantic horse mackerel (Trachurus trachurus). In
order to evaluate whether bacteriophages against Serratia could delay the
spoilage process, 11 viral strains active against this genus were isolated from
food and best candidate was applied to fresh mackerel filets. All the phages
belong to the Siphoviridae and Podoviridae families and were active at
multiplicity of infection (MOI) levels below 1:1 in Long & Hammer broth. The
ability of phage AZT6 to control Serratia populations in real food was tested in
Atlantic horse mackerel extract and applied to fresh mackerel filets. Treatment
with high phage concentration (MOI 350:1, initial Serratia population 3.9 +/- 0.3
Log cfu/g) can reduce the Serratia populations up to 90% during fish storage (a
maximum of 6 days) at low temperatures (6 degrees C). Bacterial inhibition was
dependent on the bacteriophage dosage, and MOI of 10:1 or lower did not
significantly affect the Serratia populations.
PMID- 28421037
TI - Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism.
AB - Metabolic disorders, particularly aberrations in lipid homeostasis, such as
obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest
together as the metabolic syndrome (MetS). Despite major advances in our
understanding of the pathogenesis of these disorders, the prevalence of the MetS
continues to rise. It is becoming increasingly apparent that intermediary
metabolism within the central nervous system is a major contributor to the
regulation of systemic metabolism. In particular, lipid metabolism within the
brain is tightly regulated to maintain neuronal structure and function and may
signal nutrient status to modulate metabolism in key peripheral tissues such as
the liver. There is now a growing body of evidence to suggest that fatty acid
(FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites
may signal nutritional sufficiency and may decrease hepatic glucose production,
lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted
the existence of liver-related neurons that have the potential to direct such
signals through parasympathetic and sympathetic nervous system activity. However,
to date whether these liver-related neurons are FA sensitive remain to be
determined. The findings discussed in this review underscore the importance of
the autonomic nervous system in the regulation of systemic metabolism and
highlight the need for further research to determine the key features of FA
neurons, which may serve as novel therapeutic targets for the treatment of
metabolic disorders.
PMID- 28421039
TI - Population Structure of Sclerotinia subarctica and Sclerotinia sclerotiorum in
England, Scotland and Norway.
AB - Sclerotinia species are important fungal pathogens of a wide range of crops and
wild host plants. While the biology and population structure of Sclerotinia
sclerotiorum has been well-studied, little information is available for the
related species S. subarctica. In this study, Sclerotinia isolates were collected
from different crop plants and the wild host Ranuculus ficaria (meadow buttercup)
in England, Scotland, and Norway to determine the incidence of Sclerotinia
subarctica and examine the population structure of this pathogen for the first
time. Incidence was very low in England, comprising only 4.3% of isolates while
moderate and high incidence of S. subarctica was identified in Scotland and
Norway, comprising 18.3 and 48.0% of isolates respectively. Characterization with
eight microsatellite markers identified 75 haplotypes within a total of 157
isolates over the three countries with a few haplotypes in Scotland and Norway
sampled at a higher frequency than the rest across multiple locations and host
plants. In total, eight microsatellite haplotypes were shared between Scotland
and Norway while none were shared with England. Bayesian and principal component
analyses revealed common ancestry and clustering of Scottish and Norwegian S.
subarctica isolates while English isolates were assigned to a separate population
cluster and exhibited low diversity indicative of isolation. Population structure
was also examined for S. sclerotiorum isolates from England, Scotland, Norway,
and Australia using microsatellite data, including some from a previous study in
England. In total, 484 haplotypes were identified within 800 S. sclerotiorum
isolates with just 15 shared between England and Scotland and none shared between
any other countries. Bayesian and principal component analyses revealed a common
ancestry and clustering of the English and Scottish isolates while Norwegian and
Australian isolates were assigned to separate clusters. Furthermore, sequencing
part of the intergenic spacer (IGS) region of the rRNA gene resulted in 26 IGS
haplotypes within 870 S. sclerotiorum isolates, nine of which had not been
previously identified and two of which were also widely distributed across
different countries. S. subarctica therefore has a multiclonal population
structure similar to S. sclerotiorum, but has a different ancestry and
distribution across England, Scotland, and Norway.
PMID- 28421040
TI - Isolation and Molecular Characterization of Novel Chlorpyrifos and 3,5,6
trichloro-2-pyridinol-degrading Bacteria from Sugarcane Farm Soils.
AB - Chlorpyrifos (CP) is one of the most widely used organophosphate pesticides in
agriculture worldwide, but its extensive use has led to the contamination of
various soil and water systems. Microbial bioremediation is considered to be one
of the most viable options for the removal of CP from the environment; however,
little is known about the soil bacterial diversity that degrade CP. Sequential
soil and liquid culture enrichments enabled the isolation of bacterial CP
degraders with sequence homologies to Xanthomonas sp., Pseudomonas sp., and
Rhizobium sp. The efficacy of the three isolated strains: Xanthomonas sp. 4R3-M1,
Pseudomonas sp. 4H1-M3, and Rhizobium sp. 4H1-M1 was further investigated for
biodegradation of CP and its primary metabolic product, 3,5,6-trichloro-2
pyridinol (TCP). The results indicate that all three bacterial strains almost
completely metabolized CP (10 mg/L) and TCP, occurring as a metabolic degradation
product, in mineral salt media as a sole source of carbon and nitrogen. The
isolated bacterial strains Xanthomonas sp. 4R3-M1 and Pseudomonas sp. 4H1-M3
could also degrade TCP (10 mg/L) as a sole carbon and nitrogen source, when
provided externally. Thus, these bacterial strains may be effective in practical
application of bioremediation of both CP and TCP.
PMID- 28421041
TI - Metagenome-Wide Association Study and Machine Learning Prediction of Bulk Soil
Microbiome and Crop Productivity.
AB - Areas within an agricultural field in the same season often differ in crop
productivity despite having the same cropping history, crop genotype, and
management practices. One hypothesis is that abiotic or biotic factors in the
soils differ between areas resulting in these productivity differences. In this
study, bulk soil samples collected from a high and a low productivity area from
within six agronomic fields in Illinois were quantified for abiotic and biotic
characteristics. Extracted DNA from these bulk soil samples were shotgun
sequenced. While logistic regression analyses resulted in no significant
association between crop productivity and the 26 soil characteristics, principal
coordinate analysis and constrained correspondence analysis showed crop
productivity explained a major proportion of the taxa variance in the bulk soil
microbiome. Metagenome-wide association studies (MWAS) identified more
Bradyrhizodium and Gammaproteobacteria in higher productivity areas and more
Actinobacteria, Ascomycota, Planctomycetales, and Streptophyta in lower
productivity areas. Machine learning using a random forest method successfully
predicted productivity based on the microbiome composition with the best accuracy
of 0.79 at the order level. Our study showed that crop productivity differences
were associated with bulk soil microbiome composition and highlighted several
nitrogen utility-related taxa. We demonstrated the merit of MWAS and machine
learning for the first time in a plant-microbiome study.
PMID- 28421042
TI - Mosquito Microbiome Dynamics, a Background for Prevalence and Seasonality of West
Nile Virus.
AB - Symbiotic microbial communities augment host phenotype, including defense against
pathogen carriage and infection. We sampled the microbial communities in 11 adult
mosquito host species from six regions in southern Ontario, Canada over 3 years.
Of the factors examined, we found that mosquito species was the largest driver of
the microbiota, with remarkable phylosymbiosis between host and microbiota.
Seasonal shifts of the microbiome were consistently repeated over the 3-year
period, while region had little impact. Both host species and seasonal shifts in
microbiota were associated with patterns of West Nile virus (WNV) in these
mosquitoes. The highest prevalence of WNV, with a seasonal spike each year in
August, was in the Culex pipiens/restuans complex, and high WNV prevalence
followed a decrease in relative abundance of Wolbachia in this species. Indeed,
mean temperature, but not precipitation, was significantly correlated with
Wolbachia abundance. This suggests that at higher temperatures Wolbachia
abundance is reduced leading to greater susceptibility to WNV in the subsequent
generation of C. pipiens/restuans hosts. Different mosquito genera harbored
significantly different bacterial communities, and presence or abundance of
Wolbachia was primarily associated with these differences. We identified several
operational taxonomic units (OTUs) of Wolbachia that drive overall microbial
community differentiation among mosquito taxa, locations and timepoints. Distinct
Wolbachia OTUs were consistently found to dominate microbiomes of Cx.
pipiens/restuans, and of Coquilletidia perturbans. Seasonal fluctuations of
several other microbial taxa included Bacillus cereus, Enterococcus,
Methylobacterium, Asaia, Pantoea, Acinetobacter johnsonii, Pseudomonas, and
Mycoplasma. This suggests that microbiota may explain some of the variation in
vector competence previously attributed to local environmental processes,
especially because Wolbachia is known to affect carriage of viral pathogens.
PMID- 28421043
TI - Outlining Core Pathways of Amyloid Toxicity in Bacteria with the RepA-WH1
Prionoid.
AB - The synthetic bacterial prionoid RepA-WH1 causes a vertically transmissible
amyloid proteinopathy in Escherichia coli that inhibits growth and eventually
kills the cells. Recent in vitro studies show that RepA-WH1 builds pores through
model lipid membranes, suggesting a possible mechanism for bacterial cell death.
By comparing acutely (A31V) and mildly (DeltaN37) cytotoxic mutant variants of
the protein, we report here that RepA-WH1(A31V) expression decreases the
intracellular osmotic pressure and compromise bacterial viability under either
aerobic or anaerobic conditions. Both are effects expected from threatening
membrane integrity and are in agreement with findings on the impairment by RepA
WH1(A31V) of the proton motive force (PMF)-dependent transport of ions (Fe3+) and
ATP synthesis. Systems approaches reveal that, in aerobiosis, the PMF-independent
respiratory dehydrogenase NdhII is induced in response to the reduction in
intracellular levels of iron. While NdhII is known to generate H2O2 as a by
product of the autoxidation of its FAD cofactor, key proteins in the defense
against oxidative stress (OxyR, KatE), together with other stress-resistance
factors, are sequestered by co-aggregation with the RepA-WH1(A31V) amyloid. Our
findings suggest a route for RepA-WH1 toxicity in bacteria: a primary hit of
damage to the membrane, compromising bionergetics, triggers a stroke of oxidative
stress, which is exacerbated due to the aggregation-dependent inactivation of
enzymes and transcription factors that enable the cellular response to such
injury. The proteinopathy caused by the prion-like protein RepA-WH1 in bacteria
recapitulates some of the core hallmarks of human amyloid diseases.
PMID- 28421044
TI - Comparative Genomics of Glossina palpalis gambiensis and G. morsitans morsitans
to Reveal Gene Orthologs Involved in Infection by Trypanosoma brucei gambiense.
AB - Blood-feeding Glossina palpalis gambiense (Gpg) fly transmits the single-celled
eukaryotic parasite Trypanosoma brucei gambiense (Tbg), the second Glossina fly
African trypanosome pair being Glossina morsitans/T.brucei rhodesiense. Whatever
the T. brucei subspecies, whereas the onset of their developmental program in the
zoo-anthropophilic blood feeding flies does unfold in the fly midgut, its
completion is taking place in the fly salivary gland where does emerge a low size
metacyclic trypomastigote population displaying features that account for its
establishment in mammals-human individuals included. Considering that the two
Glossina-T. brucei pairs introduced above share similarity with respect to the
developmental program of this African parasite, we were curious to map on the
Glossina morsitans morsitans (Gmm), the Differentially Expressed Genes (DEGs) we
listed in a previous study. Briefly, using the gut samples collected at days 3,
10, and 20 from Gpg that were fed or not at day 0 on Tbg-hosting mice, these DGE
lists were obtained from RNA seq-based approaches. Here, post the mapping on the
quality controlled DEGs on the Gmm genome, the identified ortholog genes were
further annotated, the resulting datasets being compared. Around 50% of the Gpg
DEGs were shown to have orthologs in the Gmm genome. Under one of the three
Glossina midgut sampling conditions, the number of DEGs was even higher when
mapping on the Gmm genome than initially recorded. Many Gmm genes annotated as
"Hypothetical" were mapped and annotated on many distinct databases allowing some
of them to be properly identified. We identify Glossina fly candidate genes
encoding (a) a broad panel of proteases as well as (b) chitin-binding proteins,
(c) antimicrobial peptide production-Pro3 protein, transferrin, mucin, atttacin,
cecropin, etc-to further select in functional studies, the objectives being to
probe and validated fly genome manipulation that prevents the onset of the
developmental program of one or the other T. brucei spp. stumpy form sampled by
one of the other bloodfeeding Glossina subspecies.
PMID- 28421045
TI - Cranberry Juice and Combinations of Its Organic Acids Are Effective against
Experimental Urinary Tract Infection.
AB - The antibacterial effect of cranberry juice and the organic acids therein on
infection by uropathogenic Escherichia coli was studied in an experimental mouse
model of urinary tract infection (UTI). Reduced bacterial counts were found in
the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially
available cranberry juice cocktail also significantly reduced (P < 0.01)
bacterial populations in the bladder, as did the hydrophilic fraction of
cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the
preponderant organic acids in cranberry juice, were tested in combination and
individually. The four organic acids also decreased bacterial levels in the
bladder when administered together (P < 0.001), and so did the combination of
malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The
other tested combinations of the organic acids, and the acids administered
singly, did not have any effect in the UTI model. Apparently, the antibacterial
effect of the organic acids from cranberry juice on UTI can be obtained by
administering a combination of malic acid and either citric or quinic acid. This
study show for the first time that cranberry juice reduce E. coli colonization of
the bladder in an experimental mouse model of urinary tract infection and that
the organic acids are active agents.
PMID- 28421046
TI - Horses in Denmark Are a Reservoir of Diverse Clones of Methicillin-Resistant and
Susceptible Staphylococcus aureus.
AB - Denmark is a country with high prevalence of livestock-associated methicillin
resistant Staphylococcus aureus (MRSA) clonal complex (CC) 398 in pigs. Even
though pig farming is regarded as the main source of human infection or
colonization with MRSA CC398, 10-15% of the human cases appear not to be linked
to pigs. Following the recent reports of MRSA CC398 in horses in other European
countries and the lack of knowledge on S. aureus carriage in this animal species,
we carried out a study to investigate whether horses constitute a reservoir of
MRSA CC398 in Denmark, and to gain knowledge on the frequency and genetic
diversity of S. aureus in horses, including both methicillin-resistant and
susceptible S. aureus (MSSA). Nasal swabs were collected from 401 horses
originating from 74 farms, either at their farms or prior to admission to
veterinary clinics. Following culture on selective media, species identification
by MALDI-TOF MS and MRSA confirmation by standard PCR-based methods, S. aureus
and MRSA were detected in 54 (13%) and 17 (4%) horses originating from 30 (40%)
and 7 (9%) farms, respectively. Based on spa typing, MSSA differed genetically
from MRSA isolates. The spa type prevalent among MSSA isolates was t127 (CC1),
which was detected in 12 horses from 11 farms and represents the most common S.
aureus clone isolated from human bacteremia cases in Denmark. Among the 17 MRSA
carriers, 10 horses from three farms carried CC398 t011 harboring the immune
evasion cluster (IEC), four horses from two farms carried IEC-negative CC398
t034, and three horses from two farms carried a mecC-positive MRSA lineage
previously associated with wildlife and domestic ruminants (CC130 t528). Based on
whole-genome phylogenetic analysis of the 14 MRSA CC398, t011 isolates belonged
to the recently identified horse-adapted clone in Europe and were closely related
to human t011 isolates from three Danish equine veterinarians, whereas t034
isolates belonged to pig-adapted clones. Our study confirms that horses carry an
equine-specific clone of MRSA CC398 that can be transmitted to veterinary
personnel, and reveals that these animals are exposed to MRSA and MSSA clones
that are likely to originate from livestock and humans, respectively.
PMID- 28421047
TI - Genetic Characterization of the Exceptionally High Heat Resistance of the Non
toxic Surrogate Clostridium sporogenes PA 3679.
AB - Clostridium sporogenes PA 3679 is a non-toxic endospore former that is widely
used as a surrogate for Clostridium botulinum by the food processing industry to
validate thermal processing strategies. PA 3679 produces spores of exceptionally
high heat resistance without botulinum neurotoxins, permitting the use of PA 3679
in inoculated pack studies while ensuring the safety of food processing
facilities. To identify genes associated with this heat resistance, the genomes
of C. sporogenes PA 3679 isolates were compared to several other C. sporogenes
strains. The most significant difference was the acquisition of a second spoVA
operon, spoVA2, which is responsible for transport of dipicolinic acid into the
spore core during sporulation. Interestingly, spoVA2 was also found in some C.
botulinum species which phylogenetically cluster with PA 3679. Most other C.
sporogenes strains examined both lack the spoVA2 locus and are phylogenetically
distant within the group I Clostridium, adding to the understanding that C.
sporogenes are dispersed C. botulinum strains which lack toxin genes. C.
sporogenes strains are thus a very eclectic group, and few strains possess the
characteristic heat resistance of PA 3679.
PMID- 28421049
TI - Transcriptomic and Metabolomics Profiling of Phage-Host Interactions between
Phage PaP1 and Pseudomonas aeruginosa.
AB - The basic biology of bacteriophage-host interactions has attracted increasing
attention due to a renewed interest in the therapeutic potential of
bacteriophages. In addition, knowledge of the host pathways inhibited by phage
may provide clues to novel drug targets. However, the effect of phage on
bacterial gene expression and metabolism is still poorly understood. In this
study, we tracked phage-host interactions by combining transcriptomic and
metabolomic analyses in Pseudomonas aeruginosa infected with a lytic
bacteriophage, PaP1. Compared with the uninfected host, 7.1% (399/5655) of the
genes of the phage-infected host were differentially expressed genes (DEGs); of
those, 354 DEGs were downregulated at the late infection phase. Many of the
downregulated DEGs were found in amino acid and energy metabolism pathways. Using
metabolomics approach, we then analyzed the changes in metabolite levels in the
PaP1-infected host compared to un-infected controls. Thymidine was significantly
increased in the host after PaP1 infection, results that were further supported
by increased expression of a PaP1-encoded thymidylate synthase gene. Furthermore,
the intracellular betaine concentration was drastically reduced, whereas choline
increased, presumably due to downregulation of the choline-glycine betaine
pathway. Interestingly, the choline-glycine betaine pathway is a potential
antimicrobial target; previous studies have shown that betB inhibition results in
the depletion of betaine and the accumulation of betaine aldehyde, the
combination of which is toxic to P. aeruginosa. These results present a detailed
description of an example of phage-directed metabolism in P. aeruginosa. Both
phage-encoded auxiliary metabolic genes and phage-directed host gene expression
may contribute to the metabolic changes observed in the host.
PMID- 28421048
TI - Functional Information Stored in the Conserved Structural RNA Domains of
Flavivirus Genomes.
AB - The genus Flavivirus comprises a large number of small, positive-sense single
stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod
and/or vertebrate host cells. The genus, which has some 70 member species,
includes a number of emerging and re-emerging pathogens responsible for outbreaks
of human disease around the world, such as the West Nile, dengue, Zika, yellow
fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis
viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that
efficiently stores all the information required for the completion of the
infectious cycle. The efficiency of this storage system is attributable to
supracoding elements, i.e., discrete, structural units with essential functions.
This information storage system overlaps and complements the protein coding
sequence and is highly conserved across the genus. It therefore offers
interesting potential targets for novel therapeutic strategies. This review
summarizes our knowledge of the features of flavivirus genome functional RNA
domains. It also provides a brief overview of the main achievements reported in
the design of antiviral nucleic acid-based drugs targeting functional genomic RNA
elements.
PMID- 28421050
TI - Reveromycins A and B from Streptomyces sp. 3-10: Antifungal Activity against
Plant Pathogenic Fungi In vitro and in a Strawberry Food Model System.
AB - This study was conducted to determine the antifungal activity of the metabolites
from Streptomyces sp. 3-10, and to purify and identify the metabolites.
Meanwhile, the taxonomic status of strain 3-10 was re-evaluated. The cultural
filtrates of strain 3-10 in potato dextrose broth were extracted with ethyl
acetate. The resulting crude extract at 1 and 5 MUg/ml inhibited growth of 22
species in 18 genera of plant pathogenic fungi and Oomycetes, accounting for 92%
of the total 24 tested species, suggesting that it has a wide antifungal
spectrum. Two compounds were purified from the crude extract and were identified
as reveromycins A and B, which demonstrated high antifungal activity against
Botrytis cinerea, Mucor hiemails, Rhizopus stolonifer, and Sclerotinia
sclerotiorum under acidic pH conditions. Both the crude extract and reveromycin A
from strain 3-10 at 10, 50, and 100 MUg/ml showed high efficacy in suppression of
strawberry fruit rot caused by the above-mentioned four pathogens. The efficacy
was comparable to that of corresponding commercial fungicides (pyrimethanil,
captan, dimetachlone) used in management of these pathogens. Morphological,
physiological, and phylogenetic characterization showed that strain 3-10 is
closely related to Streptomyces yanglinensis 1307T, representing a novel
phylotype in that species. This study reported a new strain with reveromycins
producing capability. The finding is important for further exploitation of
reveromycins for agricultural use.
PMID- 28421051
TI - In Situ Capture RT-qPCR: A New Simple and Sensitive Method to Detect Human
Norovirus in Oysters.
AB - Human noroviruses (HuNoVs) are the major cause worldwide for non-bacterial acute
gastroenteritis. In this study, we applied a novel viral receptor mediated in
situ capture RT-qPCR (ISC-RT-qPCR) to detect HuNoVs in oysters and compared with
the traditional RT-qPCR method. Ten HuNoVs RT-PCR positive and 5 negative
clinical samples from gastroenteritis patients were used to compare specificity
and sensitivity of ISC-RT-qPCR against that of the RT-qPCR assay. ISC-RT-qPCR had
at a one-log and a two-log increase in sensitivity over that of the RT-qPCR assay
for genotype I (GI) and GII, respectively. Distributions of HuNoVs in oyster
tissues were investigated in artificially inoculated oysters. GI HuNoVs could be
detected in all tissues in inoculated oysters by both ISC-RT-qPCR and RT-qPCR.
GII HuNoVs could only be detected in gills and digestive glands by both methods.
The number of viral genomic copies (vgc) measured by ISC-RT-qPCR was comparable
with RT-qPCR in the detection of GI and GII HuNoVs in inoculated oysters. Thirty
six oyster samples from local market were assayed for HuNoVs by both assays. More
HuNoVs could be detected by ISC-RT-qPCR in retail oysters. The detection rates of
GI HuNoVs in gills, digestive glands, and residual tissues were 33.3, 25.0, and
19.4% by ISC-RT-qPCR; and 5.6, 11.1, and 11.1% by RT-qPCR, respectively. The
detection rates of GII HuNoVs in gills were 2.8% by ISC-RT-qPCR; no GII HuNoV was
detected in these oysters by RT-qPCR. Overall, all results demonstrated that ISC
RT-qPCR is a promising method for detecting HuNoVs in oyster samples.
PMID- 28421052
TI - Whole Genome-Based Amplified Fragment Length Polymorphism Analysis Reveals
Genetic Diversity in Candida africana.
AB - This study aimed at investigating the genetic diversity of a panel of Candida
africana strains recovered from vaginal samples in different countries. All
fungal strains were heterozygous at the mating-type-like locus and belonged to
the genotype A of Candida albicans. Moreover, all examined C. africana strains
lack N-acetylglucosamine assimilation and sequence analysis of the HXK1 gene
showed a distinctive polymorphism that impair the utilization of this amino sugar
in this yeast. Multi-locus sequencing of seven housekeeping genes revealed a
substantial genetic homogeneity among the strains, except for the CaMPIb, SYA1
and VPS13 loci which contributed significantly to the classification of our set
of C. africana strains into six existing diploid sequence types. Amplified
fragment length polymorphism fingerprint analysis yielded greater genotypic
heterogeneity among the C. africana strains. Overall the data reported here show
that in C. africana genetic diversity occurs and the existence of this intriguing
group of C. albicans strains with specific phenotypes associated could be useful
for future comparative studies in order to better understand the genetics and
evolution of this important human pathogen.
PMID- 28421053
TI - Elevated Air Humidity Changes Soil Bacterial Community Structure in the Silver
Birch Stand.
AB - Soil microbes play a fundamental role in forest ecosystems and respond rapidly to
changes in the environment. Simultaneously with the temperature increase the
climate change scenarios also predict an intensified hydrological cycle for the
Baltic Sea runoff region. The aim of this study was to assess the effect of
elevated air humidity on the top soil microbial community structure of a silver
birch (Betula pendula Roth.) stand by using a free air humidity manipulation
facility (FAHM). The bacterial community structures of bulk soil and birch
rhizosphere were analyzed using high-throughput sequencing of bacteria
specific16S rRNA gene fragments and quantification of denitrification related
genes. The increased air humidity altered both bulk soil and rhizosphere
bacterial community structures, and changes in the bacterial communities
initiated by elevated air humidity were related to modified soil abiotic and
biotic variables. Network analysis revealed that variation in soil bacterial
community structural units is explained by altered abiotic conditions such as
increased pH value in bulk soil, while in rhizosphere the change in absorptive
root morphology had a higher effect. Among root morphological traits, the
absorptive root diameter was strongest related to the bacterial community
structure. The changes in bacterial community structures under elevated air
humidity are associated with shifts in C, N, and P turnover as well as mineral
weathering processes in soil. Increased air humidity decreased the nir and nosZ
gene abundance in the rhizosphere bacterial community. The potential contribution
of the denitrification to the N2O emission was not affected by the elevated air
humidity in birch stand soil. In addition, the study revealed a strong link
between the bacterial community structure, abundance of denitrification related
genes, and birch absorptive root morphology in the ecosystem system adaptation to
elevated air humidity.
PMID- 28421054
TI - Isolation and Characterization of Dehalobacter sp. Strain TeCB1 Including
Identification of TcbA: A Novel Tetra- and Trichlorobenzene Reductive
Dehalogenase.
AB - Dehalobacter sp. strain TeCB1 was isolated from groundwater near Sydney,
Australia, that is polluted with a range of organochlorines. The isolated strain
is able to grow by reductive dechlorination of 1,2,4,5-tetrachlorobenzene to 1,3-
and 1,4-dichlorobenzene with 1,2,4-trichlorobenzene being the intermediate
daughter product. Transient production of 1,2-dichlorobenzene was detected with
subsequent conversion to monochlorobenzene. The dehalogenation capability of
strain TeCB1 to respire 23 alternative organochlorines was examined and shown to
be limited to the use of 1,2,4,5-tetrachlorobenzene and 1,2,4-trichlorobenzene.
Growth on 1,2,4-trichlorobenzene resulted in the production of predominantly 1,3-
and 1,4-dichlorobenzene. The inability of strain TeCB1 to grow on 1,2
dichlorobenzene indicated that the production of monochlorobenzene during growth
on 1,2,4,5-tetarchlorobezene was cometabolic. The annotated genome of strain
TeCB1 contained only one detectable 16S rRNA gene copy and genes for 23 full
length and one truncated Reductive Dehalogenase (RDase) homologs, five unique to
strain TeCB1. Identification and functional characterization of the 1,2,4,5
tetrachlorobenzene and 1,2,4-trichlorobenzene RDase (TcbA) was achieved using
native-PAGE coupled with liquid chromatography tandem mass spectrometry.
Interestingly, TcbA showed higher amino acid identity with tetrachloroethene
reductases PceA (95% identity) from Dehalobacter restrictus PER-K23 and
Desulfitobacterium hafniense Y51 than with the only other chlorinated benzene
reductase [i.e., CbrA (30% identity)] functionally characterized to date.
PMID- 28421055
TI - Editorial: Genetics, Genomics and -Omics of Thermophiles.
PMID- 28421056
TI - High Prevalence of Colistin Resistance and mcr-1 Gene in Escherichia coli
Isolated from Food Animals in China.
AB - The objective of this study was to determine the minimal inhibitory concentration
of colistin for Escherichia coli from food animals and the possible underlying
colistin resistance mechanisms. During 2007-2014, 4,438 E. coli isolates of food
animal origins were collected. The susceptibility of colistin was tested by the
agar dilution method. Mutations in pmrA, pmrB, and mgrB and the presence of mcr-1
gene were determined by PCR and DNA sequencing. Complementation experiments were
carried out to evaluate the contribution of the mutations to colistin resistance.
There was a high frequency of colistin resistance in E. coli from pigs on farm
(24.1%) and at slaughter (24.3%) in 2013-2014, followed by chickens on farm
(14.0%) and at slaughter (9.5%). The resistance frequency of E. coli in cow
isolates was the lowest (0.9%). MIC distribution for colistin showed that most
isolates (75.2%) were distributed at 0.25 mg/L-0.5 mg/L, followed by 4 mg/L-8
mg/L (16.8%). Compared with the isolates from pigs and chickens recovered during
2013-2014, E. coli isolates collected during 2007-2008 (5.5%) and 2010-2011
(12.4%) showed significantly lower frequency of colistin resistance (P < 0.05).
DNA sequencing and complementation experiments failed to detect any insertion
inactivation or mutation in pmrA, pmrB, and mgrB associated with colistin
resistance. However, 91.0% colistin-resistant isolates were positive for mcr-1.
The high frequency of colistin resistance and mcr-1 gene among E. coli isolates
from food animals in China urged the need to minimize potential risks of colistin
resistance development and the spread of mcr-1 gene.
PMID- 28421058
TI - Antimicrobial Compounds Produced by Vaginal Lactobacillus crispatus Are Able to
Strongly Inhibit Candida albicans Growth, Hyphal Formation and Regulate Virulence
related Gene Expressions.
AB - The female vaginal environment contains diverse microorganisms, and their
interactions play significant roles in health and disease. Lactobacillus species
are the predominant vaginal microorganisms in healthy women and relevant as a
barrier to defense against pathogens, including Candida albicans. The yeast-to
hyphae transition is believed to be a determinant of C. albicans pathogenesis. In
this study, we investigated the effects of vaginal isolates of L. crispatus
(seven strains), L. gasseri (six strains), and L. jensenii (five strains) on
growth, hyphal formation and virulence-related genes expression of C. albicans
ATCC 10231. We found that the L. crispatus showed the most significant
antimicrobial activities in microplate-based liquid medium assay (P < 0.05). All
seven cell-free supernatants (CFS) from L. crispatus strains reduced the growth
of C. albicans by >60%. The effects might be due to their productions of some
secretory antimicrobial compounds in addition to H2O2 and organic acids.
Furthermore, each of the CFS of Lactobacillus strains was found to significantly
suppress the yeast-to-hyphae transition of C. albicans under hyphae-inducing
conditions (RPMI 1640 medium supplemented with 10% fetal bovine serum). The
hyphae inhibition rates of C. albicans treated by CFS from L. crispatus, L.
gasseri, and L. jensenii were 88.3 +/- 3.02%, 84.9 +/- 6.0%, and 81.9 +/- 6.2%,
respectively. Moreover, the expression of hyphae-specific genes (ALS3, HWP1,
ECE1, EAP1, and SAP5) and transcriptional regulatory genes (EFG1, TEC1, and NRG1)
were analyzed using quantitative real-time PCR. The results demonstrated that L.
crispatus CFS significantly down-regulated the expression of hyphae-specific
genes ALS3 (0.140-fold)), HWP1 (0.075-fold), and ECE1 (0.045-fold), while up
regulated the expression of the negative transcriptional regulator gene NRG1 with
1.911-fold. The antimicrobial compounds from L. crispatus B145 against Candida
growth were heat stable and protease resistance, but those against hyphal
formation were partially sensitive to the same treatments. Our novel findings
suggest that L. crispatus, a dominant Lactobacillus species associated with a
healthy vagina, could strongly inhibit C. albicans growth and hyphal formation.
L. crispatus might repress the expression of hyphae-specific genes (ALS3, HWP1,
and ECE1) in a NRG1-dependent manner. Besides, L. crispatus B145 is highly
worthwhile for probiotic investigation.
PMID- 28421057
TI - Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic
Fibers and Probiotics: A Review.
AB - In the present world scenario, obesity has almost attained the level of a
pandemic and is progressing at a rapid rate. This disease is the mother of all
other metabolic disorders, which apart from placing an added financial burden on
the concerned patient also has a negative impact on his/her well-being and health
in the society. Among the various plausible factors for the development of
obesity, the role of gut microbiota is very crucial. In general, the gut of an
individual is inhabited by trillions of microbes that play a significant role in
host energy homeostasis by their symbiotic interactions. Dysbiosis in gut
microbiota causes disequilibrium in energy homeostasis that ultimately leads to
obesity. Numerous mechanisms have been reported by which gut microbiota induces
obesity in experimental models. However, which microbial community is directly
linked to obesity is still unknown due to the complex nature of gut microbiota.
Prebiotics and probiotics are the safer and effective dietary substances
available, which can therapeutically alter the gut microbiota of the host. In
this review, an effort was made to discuss the current mechanisms through which
gut microbiota interacts with host energy metabolism in the context of obesity.
Further, the therapeutic approaches (prebiotics/probiotics) that helped in
positively altering the gut microbiota were discussed by taking experimental
evidence from animal and human studies. In the closing statement, the challenges
and future tasks within the field were discussed.
PMID- 28421059
TI - Phages in the Human Body.
AB - Bacteriophages, viruses that infect bacteria, have re-emerged as powerful
regulators of bacterial populations in natural ecosystems. Phages invade the
human body, just as they do other natural environments, to such an extent that
they are the most numerous group in the human virome. This was only revealed in
recent metagenomic studies, despite the fact that the presence of phages in the
human body was reported decades ago. The influence of the presence of phages in
humans has yet to be evaluated; but as in marine environments, a clear role in
the regulation of bacterial populations could be envisaged, that might have an
impact on human health. Moreover, phages are excellent vehicles of genetic
transfer, and they contribute to the evolution of bacterial cells in the human
body by spreading and acquiring DNA horizontally. The abundance of phages in the
human body does not pass unnoticed and the immune system reacts to them, although
it is not clear to what extent. Finally, the presence of phages in human samples,
which most of the time is not considered, can influence and bias microbiological
and molecular results; and, in view of the evidences, some studies suggest that
more attention needs to be paid to their interference.
PMID- 28421060
TI - The Heme Metabolite Carbon Monoxide Facilitates KSHV Infection by Inhibiting TLR4
Signaling in Endothelial Cells.
AB - Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi sarcoma (KS)
and certain rare B cell lymphoproliferative disorders. KSHV infection of
endothelial cells (EC) in vitro increases expression of the inducible host
encoded enzyme heme oxygenase-1 (HO-1), which is also strongly expressed in KS
tumors. HO-1 catalyzes the rate-limiting step in the conversion of heme into
iron, biliverdin and the gasotransmitter carbon monoxide (CO), all of which share
anti-apoptotic, anti-inflammatory, pro-survival, and tumorigenic activities. Our
previous work has shown that HO-1 expression in KSHV-infected EC is characterized
by a rapid yet transient induction at early times post-infection, followed by a
sustained upregulation co-incident with establishment of viral latency. These two
phases of expression are independently regulated, suggesting distinct roles for
HO-1 in the virus life cycle. Here, we investigated the role of HO-1 during acute
infection, prior to the onset of viral gene expression. The early infection phase
involves a series of events that culminate in delivery of the viral genome to the
nucleus. Primary infection also leads to activation of host innate immune
effectors, including the pattern recognition receptor TLR4, to induce an
antiviral response. It has been shown that TLR4-deficient EC are more susceptible
to KSHV infection than wild-type controls, suggesting an important inhibitory
role for TLR4 in the KSHV life cycle. TLR4 signaling is in turn subject to
regulation by several virus-encoded immune evasion factors. In this report we
identify HO-1 as a host protein co-opted by KSHV as part of a rapid immune
evasion strategy. Specifically, we show that early HO-1 induction by KSHV results
in increased levels of endogenous CO, which functions as a TLR4 signaling
inhibitor. In addition, we show that CO-mediated inhibition of TLR4 signaling
leads to reduced expression of TLR4-induced antiviral genes, thus dampening the
host antiviral response and facilitating KSHV infection. Conversely, inhibition
of HO-1 activity decreases intracellular CO, enhances the host antiviral response
and inhibits KSHV infection. In conclusion, this study identifies HO-1 as a novel
innate immune evasion factor in the context of KSHV infection and supports HO-1
inhibition as a viable therapeutic strategy for KS.
PMID- 28421061
TI - Comparative Analysis of the Gut Microbial Communities in Forest and Alpine Musk
Deer Using High-Throughput Sequencing.
AB - The gut ecosystem is characterized by dynamic and reciprocal interactions between
the host and bacteria. Although characterizing microbiota for herbivores has
become recognized as important tool for gauging species health, no study to date
has investigated the bacterial communities and evaluated the age-related
bacterial dynamics of musk deer. Moreover, gastrointestinal diseases have been
hypothesized to be a limiting factor of population growth in captive musk deer.
Here, high-throughput sequencing of the bacterial 16S rRNA gene was used to
profile the fecal bacterial communities in juvenile and adult alpine and forest
musk deer. The two musk deer species harbored similar bacterial communities at
the phylum level, whereas the key genera for the two species were distinct. The
bacterial communities were dominated by Firmicutes and Bacteroidetes, with the
bacterial diversity being higher in forest musk deer. The Firmicutes to
Bacteroidetes ratio also increased from juvenile to adult, while the bacterial
diversity, within-group and between-group similarity, all increased with age.
This work serves as the first sequence-based analysis of variation in bacterial
communities within and between musk deer species, and demonstrates how the gut
microbial community dynamics vary among closely related species and shift with
age. As gastrointestinal diseases have been observed in captive populations, this
study provides valuable data that might benefit captive management and future
reintroduction programs.
PMID- 28421062
TI - Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza:
Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza.
AB - Several amino acid changes have been previously implicated in adaptation of avian
influenza viruses to human hosts, among them the D701N change in the PB2
polymerase subunit that also is the main determinant of avian virus pathogenesis
in animal models. However, previous studies using recombinant viruses did not
provide conclusive information of the contribution of this PB2 residue to
pathogenicity in human influenza virus strains. We identified this mutation in an
A(H1N1)pdm09-like human influenza virus isolated from an infected patient with
pneumonia and acute respiratory failure, admitted to the intensive care unit. An
exhaustive search has revealed PB2-D701 as a highly conserved position in all
available H1N1 human virus sequences in NCBI database, showing a very low
prevalence of PB2-D701N change. Presence of PB2-701N amino acid correlates with
severe or fatal outcome in those scarce cases with known disease outcome of the
infection. In these patients, the residue PB2-701N may contribute to
pathogenicity as it was previously reported in humans infected with avian
viruses. This study helps to clarify a debate that has arisen regarding the role
of PB2-D701N in human influenza virus pathogenicity.
PMID- 28421063
TI - Editorial: Drug Development for Parasite-Induced Diarrheal Diseases.
PMID- 28421065
TI - Zika Virus Infection during Pregnancy and Congenital Abnormalities.
AB - The presence of the Zika virus (ZIKV) infection has gone ahead to be a threat to
people based on its adverse impacts. More specifically, the pregnant women have
been discouraged from traveling to the areas affected by the ZIKV because of the
likelihood of the virus causing congenital abnormalities especially the
microcephaly. The pregnant women probably attracted the virus during their first
trimester while visiting ZIKV affected territories. Although the ZIKV infected
cases have reduced in some parts of countries, the global risk assessment has not
been changed. The virus continues to spread geographically to areas where
competent vectors are present. At present, there is still no treatment of ZIKV
related illness, especially microcephaly.
PMID- 28421064
TI - Current Perspectives on Viable but Non-culturable State in Foodborne Pathogens.
AB - The viable but non-culturable (VBNC) state, a unique state in which a number of
bacteria respond to adverse circumstances, was first discovered in 1982.
Unfortunately, it has been reported that many foodborne pathogens can be induced
to enter the VBNC state by the limiting environmental conditions during food
processing and preservation, such as extreme temperatures, drying, irradiation,
pulsed electric field, and high pressure stress, as well as the addition of
preservatives and disinfectants. After entering the VBNC state, foodborne
pathogens will introduce a serious crisis to food safety and public health
because they cannot be detected using conventional plate counting techniques.
This review provides an overview of the various features of the VBNC state,
including the biological characteristics, induction and resuscitation factors,
formation and resuscitation mechanisms, detection methods, and relationship to
food safety.
PMID- 28421066
TI - Unveiling the Hybrid Genome Structure of Escherichia coli RR1 (HB101 RecA+).
AB - There have been extensive genome sequencing studies for Escherichia coli strains,
particularly for pathogenic isolates, because fast determination of pathogenic
potential and/or drug resistance and their propagation routes is crucial. For
laboratory E. coli strains, however, genome sequence information is limited
except for several well-known strains. We determined the complete genome sequence
of laboratory E. coli strain RR1 (HB101 RecA+), which has long been used as a
general cloning host. A hybrid genome sequence of K-12 MG1655 and B BL21(DE3) was
constructed based on the initial mapping of Illumina HiSeq reads to each
reference, and iterative rounds of read mapping, variant detection, and consensus
extraction were carried out. Finally, PCR and Sanger sequencing-based finishing
were applied to resolve non-single nucleotide variant regions with aberrant read
depths and breakpoints, most of them resulting from prophages and insertion
sequence transpositions that are not present in the reference genome sequence. We
found that 96.9% of the RR1 genome is derived from K-12, and identified exact
crossover junctions between K-12 and B genomic fragments. However, because RR1
has experienced a series of genetic manipulations since branching from the common
ancestor, it has a set of mutations different from those found in K-12 MG1655. As
well as identifying all known genotypes of RR1 on the basis of genomic context,
we found novel mutations. Our results extend current knowledge of the genotype of
RR1 and its relatives, and provide insights into the pedigree, genomic
background, and physiology of common laboratory strains.
PMID- 28421067
TI - C-C Motif Chemokine Ligand 2 (CCL2) Mediates Acute Lung Injury Induced by Lethal
Influenza H7N9 Virus.
AB - An avian-origin influenza A (H7N9) virus was a cause for concern in China in the
spring of 2013. Most H7N9 infections resulted in acute respiratory distress
syndrome (ARDS), which is a severe form of acute lung injury (ALI) that
contributes to morbidity and mortality. In this study, we induced viral ALI by
infecting wild-type and CCL2-deficient mice with influenza H7N9 virus. The
results suggested a close association between C-C motif chemokine ligand 2 (CCL2)
expressions and ALI induced by a lethal H7N9 virus strain (A/Hebei/01/2013).
Elevated CCL2 levels were also detected in confirmed human cases of H7N9 and the
bronchoalveolar lavage fluid (BALF) of H7N9-infected mice. Moreover, CCL2 was
overexpressed in the lung tissue of infected mice. More importantly, CCL2
deficiency ameliorated H7N9-induced ALI in mice as determined by weight loss,
survival rate, the wet:dry ratio of the lung, and pathology. Taken together, our
findings demonstrate that CCL2 is essential for H7N9 virus infection and thus
that it is a potential therapeutic target for influenza.
PMID- 28421068
TI - Model-Driven Experimentation: A New Approach to Understand Mechanisms of Tertiary
Lymphoid Tissue Formation, Function, and Therapeutic Resolution.
AB - The molecular and cellular processes driving the formation of secondary lymphoid
tissues have been extensively studied using a combination of mouse knockouts,
lineage-specific reporter mice, gene expression analysis, immunohistochemistry,
and flow cytometry. However, the mechanisms driving the formation and function of
tertiary lymphoid tissue (TLT) experimental techniques have proven to be more
enigmatic and controversial due to differences between experimental models and
human disease pathology. Systems-based approaches including data-driven
biological network analysis (gene interaction network, metabolic pathway network,
cell-cell signaling, and cascade networks) and mechanistic modeling afford a
novel perspective from which to understand TLT formation and identify mechanisms
that may lead to the resolution of tissue pathology. In this perspective, we make
the case for applying model-driven experimentation using two case studies, which
combined simulations with experiments to identify mechanisms driving lymphoid
tissue formation and function, and then discuss potential applications of this
experimental paradigm to identify novel therapeutic targets for TLT pathology.
PMID- 28421069
TI - Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't
Forget the Fuel.
AB - T-cells play a critical role in tumor immunity. Indeed, the presence of tumor
infiltrating lymphocytes is a predictor of favorable patient prognosis for many
indications and is a requirement for responsiveness to immune checkpoint blockade
therapy targeting programmed cell death 1. For tumors lacking immune infiltrate,
or for which antigen processing and/or presentation has been downregulated, a
promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell
therapy. CARs are hybrid receptors that link the tumor antigen specificity and
affinity of an antibody-derived single-chain variable fragment with signaling
endodomains associated with T-cell activation. CAR therapy targeting CD19 has
yielded extraordinary clinical responses against some hematological tumors. Solid
tumors, however, remain an important challenge to CAR T-cells due to issues of
homing, tumor vasculature and stromal barriers, and a range of obstacles in the
tumor bed. Protumoral immune infiltrate including T regulatory cells and myeloid
derived suppressor cells have been well characterized for their ability to
upregulate inhibitory receptors and molecules that hinder effector T-cells. A
critical role for metabolic barriers in the tumor microenvironment (TME) is
emerging. High glucose consumption and competition for key amino acids by tumor
cells can leave T-cells with insufficient energy and biosynthetic precursors to
support activities such as cytokine secretion and lead to a phenotypic state of
anergy or exhaustion. CAR T-cell expansion protocols that promote a less
differentiated phenotype, combined with optimal receptor design and coengineering
strategies, along with immunomodulatory therapies that also promote endogenous
immunity, offer great promise in surmounting immunometabolic barriers in the TME
and curing solid tumors.
PMID- 28421070
TI - Interplay of Regulatory T Cell and Th17 Cells during Infectious Diseases in
Humans and Animals.
AB - It is now clear that the outcome of an inflammatory process caused by infections
depends on the balance of responses by several components of the immune system.
Of particular relevance is the interplay between regulatory T cells (Tregs) and
CD4+ T cells that produce IL-17 (Th17 cells) during immunoinflammatory events. In
addition to discussing studies done in mice to highlight some unresolved issues
in the biology of these cells, we emphasize the need to include outbred animals
and humans in analyses. Achieving a balance between Treg and Th17 cells responses
represents a powerful approach to control events during immunity and
immunopathology.
PMID- 28421071
TI - Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations,
and Genotype/Phenotype Correlations.
AB - Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of
diseases caused by mutations of genes encoding proteins, which play a pivotal
role in the regulation of the inflammatory response. In the pathogenesis of AIDs,
the role of the genetic background is triggered by environmental factors through
the modulation of the innate immune system. Monogenic AIDs are characterized by
Mendelian inheritance and are caused by highly penetrant genetic variants in
single genes. During the last years, remarkable progress has been made in the
identification of disease-associated genes by using new technologies, such as
next-generation sequencing, which has allowed the genetic characterization in
undiagnosed patients and in sporadic cases by means of targeted resequencing of a
gene panel and whole exome sequencing. In this review, we delineate the genetics
of the monogenic AIDs, report the role of the most common gene mutations, and
describe the evidences of the most sound genotype/phenotype correlations in AID.
PMID- 28421072
TI - Dysregulated IL-1beta Secretion in Autoinflammatory Diseases: A Matter of Stress?
AB - Infectious and sterile inflammation is induced by activation of innate immune
cells. Triggering of toll-like receptors by pathogen-associated molecular pattern
or damage-associated molecular pattern (PAMP or DAMP) molecules generates
reactive oxygen species that in turn induce production and activation of pro
inflammatory cytokines such as IL-1beta. Recent evidence indicates that cell
stress due to common events, like starvation, enhanced metabolic demand, cold or
heat, not only potentiates inflammation but may also directly trigger it in the
absence of PAMPs or DAMPs. Stress-mediated inflammation is also a common feature
of many hereditary disorders, due to the proteotoxic effects of mutant proteins.
We propose that harmful mutant proteins can induce dysregulated IL-1beta
production and inflammation through different pathways depending on the cell type
involved. When expressed in professional inflammatory cells, stress induced by
the mutant protein activates in a cell-autonomous way the onset of inflammation
and mediates its aberrant development, resulting in the explosive responses that
hallmark autoinflammatory diseases. When expressed in non-immune cells, the
mutant protein may cause the release of transcellular stress signals that trigger
and propagate inflammation.
PMID- 28421073
TI - What Fuels Natural Killers? Metabolism and NK Cell Responses.
AB - There is a growing appreciation that cellular metabolism is important in
determining the course of lymphocyte responses. Additionally, changes in
metabolic processes have been linked to dysfunctional lymphocyte functions in a
number of different diseases. While most early studies of metabolic regulation of
lymphocyte function focused on T lymphocytes, an understanding of how metabolic
pathways impact upon natural killer (NK) cell responses is now starting to
emerge. In this review article, we will discuss how cellular metabolism
influences lymphocyte function with a particular focus upon NK cells.
PMID- 28421074
TI - Immunometabolic Phenotype Alterations Associated with the Induction of Disease
Tolerance and Persistent Asymptomatic Infection of Salmonella in the Chicken
Intestine.
AB - The adaptation of Salmonella enterica to the eukaryotic host is a key process
that enables the bacterium to survive in a hostile environment. Salmonella have
evolved an intimate relationship with its host that extends to their cellular and
molecular levels. Colonization, invasion, and replication of the bacteria in an
appropriate host suggest that modification of host functions is central to
pathogenesis. Intuitively, this subversion of the cell must be a complex process,
since hosts are not inherently programmed to provide an environment conducive to
pathogens. Hosts have evolved countermeasures to pathogen invasion,
establishment, and replication through two types of defenses: resistance and
tolerance. Resistance functions to control pathogen invasion and reduce or
eliminate the invading pathogen. Research has primarily concentrated on
resistance mechanisms that are mediated by the immune system. On the other hand,
tolerance is mediated by different mechanisms that limit the damage caused by a
pathogen's growth without affecting or reducing pathogen numbers or loads. The
mechanisms of tolerance appear to be separated into those that protect host
tissues from the virulence factors of a pathogen and those that limit or reduce
the damage caused by the host immune and inflammatory responses to the pathogen.
Some pathogens, such as Salmonella, have evolved the capacity to survive the
initial robust immune response and persist. The persistent phase of a Salmonella
infection in the avian host usually involves a complex balance of protective
immunity and immunopathology. Salmonella is able to stay in the avian ceca for
months without triggering clinical signs. Chronic colonization of the intestinal
tract is an important aspect of persistent Salmonella infection because it
results in a silent propagation of bacteria in poultry stocks due to the
impossibility to isolate contaminated animals. Data from our lab promote the
hypothesis that Salmonella have evolved a unique survival strategy in poultry
that minimizes host defenses (disease resistance) during the initial infection
and then exploits and/or induces a dramatic immunometabolic reprogramming in the
cecum that alters the host defense to disease tolerance. Unfortunately, this
disease tolerance results in the ongoing human food safety dilemma.
PMID- 28421075
TI - Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and
Inflammatory Responses via Galpha16/Akt/MAPK/NF-kappaB Signaling Pathways.
AB - EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor
critically implicated in vibratory urticaria, a rare type of allergy caused by
vibration-induced mast cell activation. In addition, EMR2 is also highly
expressed by monocyte/macrophages and has been linked to neutrophil migration and
activation. Despite these findings, little is known of EMR2-mediated signaling
and its role in myeloid biology. In this report, we show that activation of EMR2
via a receptor-specific monoclonal antibody promotes the differentiation of human
THP-1 monocytic cell line and induces the expression of pro-inflammatory
mediators, including IL-8, TNF-alpha, and MMP-9. Using specific signaling
inhibitors and siRNA knockdowns, biochemical and functional analyses reveal that
the EMR2-mediated signaling is initiated by Galpha16, followed by the subsequent
activation of Akt, extracellular signal-regulated kinase, c-Jun N-terminal
kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells. Our
results demonstrate a functional role for EMR2 in the differentiation and
inflammatory activation of human monocytic cells and provide potential targets
for myeloid cell-mediated inflammatory disorders.
PMID- 28421076
TI - Broad-Based CD4+ T Cell Responses to Influenza A Virus in a Healthy Individual
Who Lacks Typical Immunodominance Hierarchy.
AB - Influenza A virus (IAV) infection is a significant cause of morbidity and
mortality worldwide. CD4+ T cell responses have been shown to be important for
influenza protection in mouse models and in human volunteers. IAV antigen
specific CD4+ T cell responses were found to focus on matrix 1 (M1) and
nucleoprotein (NP) at the protein antigen level. At the epitope level, only
several epitopes within M1 and NP were recognized by CD4+ T cells. And the
epitope-specific CD4+ T cell responses showed a typical immunodominance hierarchy
in most of the healthy individuals studied. In this study, we reported one case
of atypical immunodominance hierarchy of CD4+ T cell responses to IAV. M1 and NP
were still the immunodominant targets of CD4+ T cell responses. However, CD4+ T
cell responses specific to 11 epitopes derived from M1 and NP were detected and
showed no significant immunodominance hierarchy. Such an atypical pattern is
likely determined by the individual's HLA alleles. These findings will help us
better understand the anti-IAV immunity as a whole and improve future vaccines
against IAV.
PMID- 28421077
TI - Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle
Exposure Is Size Specific.
AB - The application of nanotechnology in the health care setting has many potential
benefits; however, our understanding of the interactions between nanoparticles
and our immune system remains incomplete. Although many of the biological effects
of nanoparticles are negatively correlated with particle size, some are clearly
size specific and the mechanisms underlying these size-specific biological
effects remain unknown. Here, we examined the pro-inflammatory effects of silica
particles in THP-1 cells with respect to particle size; a large overall size
range with narrow intervals between particle diameters (particle diameter: 10,
30, 50, 70, 100, 300, and 1,000 nm) was used. Secretion of the pro-inflammatory
cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha induced by
exposure to the silica particles had a bell-shaped distribution, where the
maximal secretion was induced by silica nanoparticles with a diameter of 50 nm
and particles with smaller or larger diameters had progressively less effect. We
found that blockade of IL-1beta secretion markedly inhibited TNF-alpha secretion,
suggesting that IL-1beta is upstream of TNF-alpha in the inflammatory cascade
induced by exposure to silica particles, and that the induction of IL-1beta
secretion was dependent on both the NLRP3 inflammasome and on uptake of the
silica particles into the cells via endocytosis. However, a quantitative analysis
of silica particle uptake showed that IL-1beta secretion was not correlated with
the amount of silica particles taken up by the cells. Further investigation
revealed that the induction of IL-1beta secretion and uptake of silica
nanoparticles with diameters of 50 or 100 nm, but not of 10 or 1,000 nm, was
dependent on scavenger receptor (SR) A1. In addition, of the silica particles
examined, only those with a diameter of 50 nm induced strong IL-1beta secretion
via activation of Mer receptor tyrosine kinase, a signal mediator of SR A1.
Together, our results suggest that the SR A1-mediated pro-inflammatory response
is dependent on ligand size and that both SR A1-mediated endocytosis and receptor
mediated signaling are required to produce the maximal pro-inflammatory response
to exposure to silica particles.
PMID- 28421079
TI - Severe Sequelae to Mold-Related Illness as Demonstrated in Two Finnish Cohorts.
AB - The presence of toxic indoor molds with accompanying bacterial growth is clearly
detrimental to human health. The pathophysiological and toxicological effects of
toxins and structural components of molds and bacteria have been clarified in
experiments conducted in tissue culture and animals, and there is convincing
epidemiologic evidence; nonetheless their implications for human health are
either ignored or denied, at least in Finland. In this communication, we describe
two cohorts suffering severe sequelae to mold-related illness. One cohort is a
nine-member family with pets that moved into a new house, which soon proved to be
infested with pathogenic molds. The other cohort consists of 30 teachers and 50
students from a mold-infested school building. The first cohort experienced a
plethora of mucosal irritation, neurological, skin, allergic, and other symptoms,
with all family members ultimately developing a multiple chemical syndrome. In
the second cohort, we detected a greatly elevated prevalence of autoimmune
conditions and malignancies. We claim that mold-related illness exists in
multiple facets; if not simply a transient mucosal irritation or even an
increased risk of asthma onset or its exacerbation. We propose a scheme to
explain the natural course of the mold-related illness. We recommend that future
studies should combine data from, e.g., cancer, autoimmune, and endocrine
disorder registers and neurological and mental health or neuropsychological
registers with mold-exposed individuals being monitored for prolonged follow-up
times.
PMID- 28421080
TI - B Cell Functions Can Be Modulated by Antimicrobial Peptides in Rainbow Trout
Oncorhynchus mykiss: Novel Insights into the Innate Nature of B Cells in Fish.
AB - B cells in fish were recently proven to have potent innate immune activities like
macrophages. This inspired us to further explore the innate nature of B cells in
fish. Moreover, antimicrobial peptides (AMPs) are representative molecules of
innate immunity, and they can modulate the functions of macrophages. These make
fish an appropriate model to study the interactions between B cells and AMPs.
Interestingly, the results in this study revealed that the IgM+ and IgT+ B cells
of rainbow trout could express multiple AMP genes, including four cathelicidin
genes and one beta-defensin gene. The expression levels of the cathelicidin genes
were obviously higher than that of the beta-defensin gene. Further studies
revealed that intracellular, extracellular, in vitro, and in vivo stimulations
could significantly increase the expression of the cathelicidin genes in trout
IgM+ and IgT+ B cells but not the expression of the beta-defensin gene,
indicating that cathelicidin peptides are the main innate immune effectors of
trout B cells. More interestingly, we found that cathelicidin peptides could
significantly enhance the phagocytic, intracellular bactericidal, and reactive
oxygen species activities of trout IgM+ and IgT+ B cells, a phenomenon previously
reported only in macrophages, and these activities might also be mediated by the
P2X7 receptor. These results collectively suggest that B cells play multiple
roles in the innate immunity of fish, and they provide new evidence for
understanding the close relationship between B cells and macrophages in
vertebrates.
PMID- 28421078
TI - Genetic Association of Hematopoietic Stem Cell Transplantation Outcome beyond
Histocompatibility Genes.
AB - The outcome of hematopoietic stem cell transplantation (HSCT) is controlled by
genetic factors among which the leukocyte antigen human leukocyte antigen (HLA)
matching is most important. In addition, minor histocompatibility antigens and
non-HLA gene polymorphisms in genes controlling immune responses are known to
contribute to the risks associated with HSCT. Besides single-nucleotide
polymorphisms (SNPs) in protein coding genes, SNPs in regulatory elements such as
microRNAs (miRNAs) contribute to these genetic risks. However, genetic risks
require for their realization the expression of the respective gene or miRNA.
Thus, gene and miRNA expression studies may help to identify genes and SNPs that
indeed affect the outcome of HSCT. In this review, we summarize gene expression
profiling studies that were performed in recent years in both patients and animal
models to identify genes regulated during HSCT. We discuss SNP-mRNA-miRNA
regulatory networks and their contribution to the risks associated with HSCT in
specific examples, including forkheadbox protein 3 and regulatory T cells, the
role of the miR-155 and miR-146a regulatory network for graft-versus-host
disease, and the function of MICA and its receptor NKG2D for the outcome of HSCT.
These examples demonstrate how SNPs affect expression or function of proteins
that modulate the alloimmune response and influence the outcome of HSCT. Specific
miRNAs targeting these genes and directly affecting expression of mRNAs are
identified. It might be valuable in the future to determine SNPs and to analyze
miRNA and mRNA expression in parallel in cohorts of HSCT patients to further
elucidate genetic risks of HSCT.
PMID- 28421081
TI - Mechanistic Insight into Salt Tolerance of Acacia auriculiformis: The Importance
of Ion Selectivity, Osmoprotection, Tissue Tolerance, and Na+ Exclusion.
AB - Salinity, one of the major environmental constraints, threatens soil health and
consequently agricultural productivity worldwide. Acacia auriculiformis, being a
halophyte, offers diverse benefits against soil salinity; however, the defense
mechanisms underlying salt-tolerant capacity in A. auriculiformis are still
elusive. In this study, we aimed to elucidate mechanisms regulating the
adaptability of the multi-purpose perennial species A. auriculiformis to salt
stress. The growth, ion homeostasis, osmoprotection, tissue tolerance and Na+
exclusion, and anatomical adjustments of A. auriculiformis grown in varied doses
of seawater for 90 and 150 days were assessed. Results showed that diluted
seawater caused notable reductions in the level of growth-related parameters,
relative water content, stomatal conductance, photosynthetic pigments, proteins,
and carbohydrates in dose- and time-dependent manners. However, the percent
reduction of these parameters did not exceed 50% of those of control plants. Na+
contents in phyllodes and roots increased with increasing levels of salinity,
whereas K+ contents and K+/Na+ ratio decreased significantly in comparison with
control plants. A. auriculiformis retained more Na+ in the roots and maintained
higher levels of K+, Ca2+ and Mg2+, and K+/Na+ ratio in phyllodes than roots
through ion selective capacity. The contents of proline, total free amino acids,
total sugars and reducing sugars significantly accumulated together with the
levels of malondialdehyde and electrolyte leakage in the phyllodes, particularly
at day 150th of salt treatment. Anatomical investigations revealed various
anatomical changes in the tissues of phyllodes, stems and roots by salt stress,
such as increase in the size of spongy parenchyma of phyllodes, endodermal
thickness of stems and roots, and the diameter of root vascular bundle, relative
to control counterparts. Furthermore, the estimated values for Na+ exclusion and
tissue tolerance index suggested that A. auriculiformis efficiently adopted these
two mechanisms to address higher salinity levels. Our results conclude that the
adaptability of A. auriculiformis to salinity is closely associated with ion
selectivity, increased accumulation of osmoprotectants, efficient Na+ retention
in roots, anatomical adjustments, Na+ exclusion and tissue tolerance mechanisms.
PMID- 28421082
TI - Insights into the Structure, Function, and Ion-Mediated Signaling Pathways
Transduced by Plant Integrin-Linked Kinases.
AB - Kinases facilitate detection of extracellular signals and set in motion cellular
responses for plant adaptation and survival. Some of the energy utilized for
kinase signal processing is produced through the activity of ion transporters.
Additionally, the synergy between cellular ions and signal transduction
influences plant response to pathogens, and their growth and development. In
plants, the signaling elements that connect cell wall and membrane sensors with
ion homeostasis and transport-mediated processes are largely unknown. Current
research indicates that plant Integrin-Linked Kinases (ILKs), a subfamily Raf
like MAP2K Kinases, may have evolved to fulfill this role. In this review, we
explore new findings on plant ILKs placing a particular focus on the connection
between ILKs proteins unique structural features and ILKs functions. The ankyrin
repeat motifs and the kinase domains of ILKs in Arabidopsis and land plants
lineage, respectively, are analyzed and discussed as potential determinants of
ILKs' metal ion cofactor specificity and their enzymatic and interaction
activities. Further, ILKs regulation through gene expression, subcellular
localization, and ions and ion transporters is reviewed in the context of recent
studies. Finally, using evidence from literature and interactomics databanks, we
infer ILKs-dependent cellular pathways and highlight their potential in
transmitting multiple types of signals originating at the interface between the
cell wall and plasma membrane.
PMID- 28421083
TI - LTRtype, an Efficient Tool to Characterize Structurally Complex LTR
Retrotransposons and Nested Insertions on Genomes.
AB - The amplification and recombination of long terminal repeat (LTR)
retrotransposons have proven to determine the size, organization, function, and
evolution of most host genomes, especially very large plant genomes. However, the
limitation of tools for an efficient discovery of structural complexity of LTR
retrotransposons and the nested insertions is a great challenge to confront ever
growing amount of genomic sequences for many organisms. Here we developed a novel
software, called as LTRtype, to characterize different types of structurally
complex LTR retrotransposon elements as well as nested events. This system is
capable of rapidly scanning large-scale genomic sequences and appropriately
characterizing the five complex types of LTR retrotransposon elements. After
testing on the Arabidopsis thaliana genome, we found that this program is able to
properly annotate a large number of structurally complex elements as well as the
nested insertions. Thus, LTRtype can be employed as an automatic and efficient
tool that will help to reconstruct the evolutionary history of LTR
retrotransposons and better understand the evolution of host genomes. LTRtype is
publicly available at: http://www.plantkingdomgdb.com/LTRtype/index.html.
PMID- 28421084
TI - Characterization of the Heme Pocket Structure and Ligand Binding Kinetics of Non
symbiotic Hemoglobins from the Model Legume Lotus japonicus.
AB - Plant hemoglobins (Hbs) are found in nodules of legumes and actinorhizal plants
but also in non-symbiotic organs of monocots and dicots. Non-symbiotic Hbs
(nsHbs) have been classified into two phylogenetic groups. Class 1 nsHbs show an
extremely high O2 affinity and are induced by hypoxia and nitric oxide (NO),
whereas class 2 nsHbs have moderate O2 affinity and are induced by cold and
cytokinins. The functions of nsHbs are still unclear, but some of them rely on
the capacity of hemes to bind diatomic ligands and catalyze the NO dioxygenase
(NOD) reaction (oxyferrous Hb + NO -> ferric Hb + nitrate). Moreover, NO may
nitrosylate Cys residues of proteins. It is therefore important to determine the
ligand binding properties of the hemes and the role of Cys residues. Here, we
have addressed these issues with the two class 1 nsHbs (LjGlb1-1 and LjGlb1-2)
and the single class 2 nsHb (LjGlb2) of Lotus japonicus, which is a model legume
used to facilitate the transfer of genetic and biochemical information into
crops. We have employed carbon monoxide (CO) as a model ligand and resonance
Raman, laser flash photolysis, and stopped-flow spectroscopies to unveil major
differences in the heme environments and ligand binding kinetics of the three
proteins, which suggest non-redundant functions. In the deoxyferrous state,
LjGlb1-1 is partially hexacoordinate, whereas LjGlb1-2 shows complete
hexacoordination (behaving like class 2 nsHbs) and LjGlb2 is mostly
pentacoordinate (unlike other class 2 nsHbs). LjGlb1-1 binds CO very strongly by
stabilizing it through hydrogen bonding, but LjGlb1-2 and LjGlb2 show lower CO
stabilization. The changes in CO stabilization would explain the different
affinities of the three proteins for gaseous ligands. These affinities are
determined by the dissociation rates and follow the order LjGlb1-1 > LjGlb1-2 >
LjGlb2. Mutations LjGlb1-1 C78S and LjGlb1-2 C79S caused important alterations in
protein dynamics and stability, indicating a structural role of those Cys
residues, whereas mutation LjGlb1-1 C8S had a smaller effect. The three proteins
and their mutant derivatives exhibited similarly high rates of NO consumption,
which were due to NOD activity of the hemes and not to nitrosylation of Cys
residues.
PMID- 28421085
TI - Expression of Arabidopsis SHN1 in Indian Mulberry (Morus indica L.) Increases
Leaf Surface Wax Content and Reduces Post-harvest Water Loss.
AB - Mulberry (Morus species) leaf is the sole food for monophagous silkworms, Bombyx
mori L. Abiotic stresses such as drought, salinity, and high temperature,
significantly decrease mulberry productivity and post-harvest water loss from
leaves influence silkworm growth and cocoon yield. Leaf surface properties
regulate direct water loss through the cuticular layer. Leaf surface waxes,
contribute for cuticular resistance and protect mesophyll cells from desiccation.
In this study we attempted to overexpress AtSHN1, a transcription factor
associated with epicuticular wax biosynthesis to increase leaf surface wax load
in mulberry. Agrobacterium mediated in vitro transformation was carried out using
hypocotyl and cotyledonary explants of Indian mulberry (cv. M5). Mulberry
transgenic plants expressing AtSHN1 displayed dark green shiny appearance with
increased leaf surface wax content. Scanning electron microscopy (SEM) and gas
chromatograph-mass spectrometry (GC-MS) analysis showed change in pattern of
surface wax deposition and significant change in wax composition in AtSHN1
overexpressors. Increased wax content altered leaf surface properties as there
was significant difference in water droplet contact angle and diameter between
transgenic and wild type plants. The transgenic plants showed significant
improvement in leaf moisture retention capacity even 5 h after harvest and there
was slow degradation of total buffer soluble protein in detached leaves compared
to wild type. Silkworm bioassay did not indicate any undesirable effects on
larval growth and cocoon yield. This study demonstrated that expression of
AtSHN1, can increase surface wax load and reduce the post-harvest water loss in
mulberry.
PMID- 28421086
TI - Association Analysis of Markers Derived from Starch Biosynthesis Related Genes
with Starch Physicochemical Properties in the USDA Rice Mini-Core Collection.
AB - Rice eating and cooking quality is largely determined by starch physicochemical
properties. The diverse accessions in the USDA rice mini-core collection (URMC)
facilitate extensive association analysis of starch physicochemical properties
with molecular markers specific to starch biosynthesis related genes. To identify
significant trait-marker associations that can be utilized in rice breeding
programs for improved starch quality, we conducted two association analyses
between 26 molecular markers derived from starch biosynthesis related genes and
18 parameters measured of starch physicochemical properties in two sets of the
mini-core accessions successfully grown in two environments in China. Many
significant trait-marker associations (P < 0.001) were detected in both
association analyses. Five markers of Waxy gene, including the (CT)n repeats, the
G/T SNP of intron 1, the 23 bp sequence duplication (InDel) of exon 2, the A/C
SNP of exon 6, and the C/T SNP of exon 10, were found to be primarily associated
with starch traits related to apparent amylose content (AAC), and two markers
targeting the 4,329-4,330 bp GC/TT SNPs and 4,198 bp G/A SNP of SSIIa gene were
mainly associated with traits related to gelatinization temperature (GT). Two new
haplotypes were found in the mini-core collection based on the combinations of
the 23 bp InDel and three SNPs (G/T of intron 1, A/C of exon 6, and C/T of exon
10) of Waxy gene. Furthermore, our analyses indicated that the (CT)n
polymorphisms of Waxy gene had a non-negligible effect on AAC related traits, as
evidenced by significant variation in AAC related traits among rice accessions
with the same Waxy SNPs but different (CT) n repeats. As the five Waxy markers
and the two SSIIa markers showed consistent major effects on starch quality
traits across studies, these markers should have priority for utilization in
marker-assisted breeding.
PMID- 28421088
TI - Non-host Resistance: DNA Damage Is Associated with SA Signaling for Induction of
PR Genes and Contributes to the Growth Suppression of a Pea Pathogen on Pea
Endocarp Tissue.
AB - Salicylic acid (SA) has been reported to induce plant defense responses. The
transcriptions of defense genes that are responsible for a given plant's
resistance to an array of plant pathogens are activated in a process called non
host resistance. Biotic signals capable of carrying out the activation of
pathogenesis-related (PR) genes in pea tissue include fungal DNase and chitosan,
two components released from Fusarium solani spores that are known to target host
DNA. Recent reports indicate that SA also has a physical affinity for DNA. Here,
we report that SA-induced reactive oxygen species release results in fragment
alterations in pea nuclear DNA and cytologically detectable diameter and
structural changes in the pea host nuclei. Additionally, we examine the
subsequent SA-related increase of resistance to the true pea pathogen F. solani
f.sp. pisi and the accumulation of the phytoalexin pisatin. This is the first
report showing that SA-induced PR gene activation may be attributed to the host
pea genomic DNA damage and that at certain concentrations, SA can be temporally
associated with subsequent increases in the defense response of this legume.
PMID- 28421089
TI - Using a Structural Root System Model to Evaluate and Improve the Accuracy of Root
Image Analysis Pipelines.
AB - Root system analysis is a complex task, often performed with fully automated
image analysis pipelines. However, the outcome is rarely verified by ground-truth
data, which might lead to underestimated biases. We have used a root model,
ArchiSimple, to create a large and diverse library of ground-truth root system
images (10,000). For each image, three levels of noise were created. This library
was used to evaluate the accuracy and usefulness of several image descriptors
classically used in root image analysis softwares. Our analysis highlighted that
the accuracy of the different traits is strongly dependent on the quality of the
images and the type, size, and complexity of the root systems analyzed. Our study
also demonstrated that machine learning algorithms can be trained on a synthetic
library to improve the estimation of several root system traits. Overall, our
analysis is a call to caution when using automatic root image analysis tools. If
a thorough calibration is not performed on the dataset of interest, unexpected
errors might arise, especially for large and complex root images. To facilitate
such calibration, both the image library and the different codes used in the
study have been made available to the community.
PMID- 28421087
TI - Evolutionary Analysis of the LAFL Genes Involved in the Land Plant Seed
Maturation Program.
AB - Seeds are one of the most significant innovations in the land plant lineage,
critical to the diversification and adaptation of plants to terrestrial
environments. From perspective of seed evo-devo, the most crucial developmental
stage in this innovation is seed maturation, which includes accumulation of
storage reserves, acquisition of desiccation tolerance, and induction of
dormancy. Based on previous studies of seed development in the model plant
Arabidopsis thaliana, seed maturation is mainly controlled by the LAFL regulatory
network, which includes LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) of the NF-YB
gene family, and ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2
(LEAFY COTYLEDON2) of the B3-AFL gene family. In the present study, molecular
evolution of these LAFL genes was analyzed, using representative species from
across the major plant lineages. Additionally, to elucidate the molecular
mechanisms of the seed maturation program, co-expression pattern analyses of LAFL
genes were conducted across vascular plants. The results show that the origin of
AFL gene family dates back to a common ancestor of bryophytes and vascular
plants, while LEC1-type genes are only found in vascular plants. LAFL genes of
vascular plants likely specify their co-expression in two different developmental
phrases, spore and seed maturation, respectively, and expression patterns vary
slightly across the major vascular plants lineages. All the information presented
in this study will provide insights into the origin and diversification of seed
plants.
PMID- 28421090
TI - Comparative Genomics and Phylogenomics of East Asian Tulips (Amana, Liliaceae).
AB - The genus Amana Honda (Liliaceae), when it is treated as separate from Tulipa,
comprises six perennial herbaceous species that are restricted to China, Japan
and the Korean Peninsula. Although all six Amana species have important medicinal
and horticultural uses, studies focused on species identification and molecular
phylogenetics are few. Here we report the nucleotide sequences of six complete
Amana chloroplast (cp) genomes. The cp genomes of Amana range from 150,613 bp to
151,136 bp in length, all including a pair of inverted repeats (25,629-25,859 bp)
separated by the large single-copy (81,482-82,218 bp) and small single-copy
(17,366-17,465 bp) regions. Each cp genome equivalently contains 112 unique genes
consisting of 30 transfer RNA genes, four ribosomal RNA genes, and 78 protein
coding genes. Gene content, gene order, AT content, and IR/SC boundary structure
are nearly identical among all Amana cp genomes. However, the relative
contraction and expansion of the IR/SC borders among the six Amana cp genomes
results in length variation among them. Simple sequence repeat (SSR) analyses of
these Amana cp genomes indicate that the richest SSRs are A/T mononucleotides.
The number of repeats among the six Amana species varies from 54 (A. anhuiensis)
to 69 (Amana kuocangshanica) with palindromic (28-35) and forward repeats (23-30)
as the most common types. Phylogenomic analyses based on these complete cp
genomes and 74 common protein-coding genes strongly support the monophyly of the
genus, and a sister relationship between Amana and Erythronium, rather than a
shared common ancestor with Tulipa. Nine DNA markers (rps15-ycf1, accD-psaI, petA
psbJ, rpl32-trnL, atpH-atpI, petD-rpoA, trnS-trnG, psbM-trnD, and ycf4-cemA) with
number of variable sites greater than 0.9% were identified, and these may be
useful for future population genetic and phylogeographic studies of Amana
species.
PMID- 28421091
TI - Oil Palm and Rubber Tree Water Use Patterns: Effects of Topography and Flooding.
AB - Oil palm and rubber plantations extend over large areas and encompass
heterogeneous site conditions. In periods of high rainfall, plants in valleys and
at riparian sites are more prone to flooding than plants at elevated topographic
positions. We asked to what extent topographic position and flooding affect oil
palm and rubber tree water use patterns and thereby influence spatial and
temporal heterogeneity of transpiration. In an undulating terrain in the lowlands
of Jambi, Indonesia, plantations of the two species were studied in plot pairs
consisting of upland and adjacent valley plots. All upland plots were non
flooded, whereas the corresponding valley plots included non-flooded, long-term
flooded, and short-term flooded conditions. Within each plot pair, sap flux
densities in palms or trees were monitored simultaneously with thermal
dissipation probes. In plot pairs with non-flooded valleys, sap flux densities of
oil palms were only slightly different between the topographic positions, whereas
sap flux densities of rubber trees were higher in the valley than at the
according upland site. In pairs with long-term flooded valleys, sap flux
densities in valleys were lower than at upland plots for both species, but the
reduction was far less pronounced in oil palms than in rubber trees (-22 and -45%
in maximum sap flux density, respectively). At these long-term flooded valley
plots palm and tree water use also responded less sensitively to fluctuations in
micrometeorological variables than at upland plots. In short-term flooded valley
plots, sap flux densities of oil palm were hardly affected by flooding, but sap
flux densities of rubber trees were reduced considerably. Topographic position
and flooding thus affected water use patterns in both oil palms and rubber trees,
but the changes in rubber trees were much more pronounced: compared to non
flooded upland sites, the different flooding conditions at valley sites amplified
the observed heterogeneity of plot mean water use by a factor of 2.4 in oil palm
and by a factor of 4.2 in rubber plantations. Such strong differences between
species as well as the pronounced heterogeneity of water use across space and
time may be of relevance for eco-hydrological assessments of tropical plantation
landscapes.
PMID- 28421092
TI - Manipulation of ABA Content in Arabidopsis thaliana Modifies Sensitivity and
Oxidative Stress Response to Dickeya dadantii and Influences Peroxidase Activity.
AB - The production of reactive oxygen species (ROS) is one of the first defense
reactions induced in Arabidopsis in response to infection by the pectinolytic
enterobacterium Dickeya dadantii. Previous results also suggest that abscisic
acid (ABA) favors D. dadantii multiplication and spread into its hosts. Here, we
confirm this hypothesis using ABA-deficient and ABA-overproducer Arabidopsis
plants. We investigated the relationships between ABA status and ROS production
in Arabidopsis after D. dadantii infection and showed that ABA status modulates
the capacity of the plant to produce ROS in response to infection by decreasing
the production of class III peroxidases. This mechanism takes place independently
of the well-described oxidative stress related to the RBOHD NADPH oxidase. In
addition to this weakening of plant defense, ABA content in the plant correlates
positively with the production of some bacterial virulence factors during the
first stages of infection. Both processes should enhance disease progression in
presence of high ABA content. Given that infection increases transcript abundance
for the ABA biosynthesis genes AAO3 and ABA3 and triggers ABA accumulation in
leaves, we propose that D. dadantii manipulates ABA homeostasis as part of its
virulence strategy.
PMID- 28421093
TI - Enhanced Growth Performance and Salinity Tolerance in Transgenic Switchgrass via
Overexpressing Vacuolar Na+ (K+)/H+ Antiporter Gene (PvNHX1).
AB - Switchgrass (Panicum virgatum L.) has been increasingly recognized as one of the
most valuable perennial bioenergy crop. To improve its biomass production,
especially under salt stress, we isolated a putative vacuolar Na+ (K+)/H+
antiporter gene from switchgrass and designated as PvNHX1. Subcellular
localization revealed that this protein was localized mainly on the vacuole
membrane. The PvNHX1 was found to be expressed throughout the entire growth
period of switchgrass, exhibited preferentially expressed in the leaf tissue, and
highly induced by salt stress. Transgenic switchgrass overexpressing PvNHX1
showed obvious advantages with respect to plant height and leaf development
compared to the wild-type (WT) and transgenic control (EV, expressing the empty
vector only) plants, suggesting PvNHX1 may serve as a promoter in switchgrass
growth and development. Moreover, transgenic switchgrass were more tolerant than
control plants with better growth-related phenotypes (higher shoot height, larger
stem diameter, longer leaf length, and width) and physiological capacities
(increased proline accumulation, reduced malondialdehyde production, preserved
cell membrane integrity, etc.) under high salinity stress. Furthermore, the genes
related to cell growth, flowering, and potassium transporters in transgenic
switchgrass exhibited a different expression profiles when compared to the
control plants, indicating a pivotal function of PvNHX1 in cell expansion and K+
homeostasis. Taken together, PvNHX1 is essential for normal plant growth and
development, and play an important role in the response to salt stress by
improving K+ accumulation. Our data provide a valuable foundation for further
researches on the molecular mechanism and physiological roles of NHXs in plants.
PMID- 28421094
TI - Cucumber CsBPCs Regulate the Expression of CsABI3 during Seed Germination.
AB - Cucumber seeds with shallow dormancy start to germinate in fruit that are
harvested late. ABSCISIC ACID INSENSITIVE3 (ABI3), a transcription factor in the
abscisic acid (ABA) signaling pathway, is one of the most important regulators in
the transition from late embryogenesis to germination. Our analysis found a
candidate cis-regulatory motif for cucumber BASIC PENTACYSTEINE (CsBPC) in the
promoter of CsABI3. Yeast one-hybrid and chromatin immunoprecipitation (ChIP)
assays showed that CsBPCs bound to the promoter of CsABI3. Examination of beta
glucuronidase (GUS) activity driven by the CsABI3 promoter in transgenic
Arabidopsis thaliana plants overexpressing CsBPCs and a Nicotiana benthamiana
(tobacco) luciferase assay indicated that CsBPCs inhibited the expression of
CsABI3. Transgenic plants overexpressing CsBPCs were constructed to confirm that
CsBPCs participates in the control of seed germination. This study of the
cucumber BPC-ABI3 pathway will help to explore and characterize the molecular
mechanisms underlying seed germination and will provide necessary information for
seed conservation in agriculture and forestry.
PMID- 28421095
TI - Exploiting Wild Relatives for Genomics-assisted Breeding of Perennial Crops.
AB - Perennial crops are vital contributors to global food production and nutrition.
However, the breeding of new perennial crops is an expensive and time-consuming
process due to the large size and lengthy juvenile phase of many species.
Genomics provides a valuable tool for improving the efficiency of breeding by
allowing progeny possessing a trait of interest to be selected at the seed or
seedling stage through marker-assisted selection (MAS). The benefits of MAS to a
breeder are greatest when the targeted species takes a long time to reach
maturity and is expensive to grow and maintain. Thus, MAS holds particular
promise in perennials since they are often costly and time-consuming to grow to
maturity and evaluate. Well-characterized germplasm that breeders can tap into
for improving perennials is often limited in genetic diversity. Wild relatives
are a largely untapped source of desirable traits including disease resistance,
fruit quality, and rootstock characteristics. This review focuses on the use of
genomics-assisted breeding in perennials, especially as it relates to the
introgression of useful traits from wild relatives. The identification of genetic
markers predictive of beneficial phenotypes derived from wild relatives is
hampered by genomic tools designed for domesticated species that are often ill
suited for use in wild relatives. There is therefore an urgent need for better
genomic resources from wild relatives. A further barrier to exploiting wild
diversity through genomics is the phenotyping bottleneck: well-powered genetic
mapping requires accurate and cost-effective characterization of large
collections of diverse wild germplasm. While genomics will always be used in
combination with traditional breeding methods, it is a powerful tool for
accelerating the speed and reducing the costs of breeding while harvesting the
potential of wild relatives for improving perennial crops.
PMID- 28421096
TI - Regulation of Banana Phytoene Synthase (MaPSY) Expression, Characterization and
Their Modulation under Various Abiotic Stress Conditions.
AB - Phytoene synthase (PSY) is a key regulatory enzyme of carotenoid biosynthesis
pathway in plants. The present study examines the role of PSY in carotenogenesis
and stress management in banana. Germplasm screening of 10 Indian cultivars
showed that Nendran (3011.94 MUg/100 g dry weight) and Rasthali (105.35 MUg/100 g
dry weight) contained the highest and lowest amounts of beta-carotene,
respectively in ripe fruit-pulp. Nendran ripe pulp also showed significantly
higher antioxidant activity as compared to Rasthali. Meta-analysis of three
banana PSY genes (MaPSY1, MaPSY2, and MaPSY3) was performed to identify their
structural features, subcellular, and chromosomal localization in banana genome.
The distinct expression patterns of MaPSY1, MaPSY2, and MaPSY3 genes were
observed in various tissues, and fruit developmental stages of these two
contrasting cultivars, suggesting differential regulation of the banana PSY
genes. A positive correlation was observed between the expression of MaPSY1 and
beta-carotene accumulation in the ripe fruit-peel and pulp of Nendran. The
presence of stress responsive cis-regulatory motifs in promoter region of MaPSY
genes were correlated with the expression pattern during various stress (abscisic
acid, methyl jasmonate, salicylic acid and dark) treatments. The positive
modulation of MaPSY1 noticed under abiotic stresses suggested its role in plant
physiological functions and defense response. The amino acid sequence analysis of
the PSY proteins in contrasting cultivars revealed that all PSY comprises
conserved domains related to enzyme activity. Bacterial complementation assay has
validated the functional activity of six PSY proteins and among them PSY1 of
Nendran (Nen-PSY1) gave the highest activity. These data provide new insights
into the regulation of PSY expression in banana by developmental and stress
related signals that can be explored in the banana improvement programs.
PMID- 28421097
TI - Development of Incompletely Fused Carpels in Maize Ovary Revealed by miRNA,
Target Gene and Phytohormone Analysis.
AB - Although the molecular basis of carpel fusion in maize ovary development remains
largely unknown, increasing evidence suggests a critical role of microRNAs
(miRNAs). In this study, a combination of miRNA sequencing, degradome and
physiological analyses was used to characterize carpel fusion development in
maize ovaries showing incompletely (IFC) and completely fused carpels (CFC). A
total of 162 known miRNAs distributed across 33 families were identified, of
which 20 were differentially expressed. In addition, 53 miRNA candidates were
identified, of which 10 were differentially expressed in the IFC and CFC ovaries.
In degradome analysis, a total of 113 and 11 target genes were predicted for the
known and novel miRNAs, respectively. Moreover, 24 (60%) target genes of the
differentially expressed known miRNAs were found to code transcription factors,
including auxin response factor (ARF), TB1-CYC-PCFs (TCP), APETALA2 (AP2), growth
regulating factor (GRF), MYB, NAC, and NF-YA, all of which have been shown to
play a role in carpel fusion development. Correlation analysis of these
differentially expressed known miRNAs and their targets with phytohormone signals
revealed significant correlations with at least one phytohormone signal, the main
regulator of carpel fusion development. These results suggest that incomplete
carpel fusion is partly the result of differential expression of certain miRNAs
and their targets. Overall, these findings improve our knowledge of the effect of
miRNA regulation on target expression, providing a useful resource for further
analysis of the interactions between miRNAs, target genes and phytohormones
during carpel fusion development in maize.
PMID- 28421098
TI - Fine-Mapping the Branching Habit Trait in Cultivated Peanut by Combining Bulked
Segregant Analysis and High-Throughput Sequencing.
AB - The growth habit of lateral shoots (also termed "branching habit") is an
important descriptive and agronomic character of peanut. Yet, both the
inheritance of branching habit and the genetic mechanism that controls it in this
crop remain unclear. In addition, the low degree of polymorphism among cultivated
peanut varieties hinders fine-mapping of this and other traits in non-homozygous
genetic structures. Here, we combined high-throughput sequencing with a well
defined genetic system to study these issues in peanut. Initially, segregating F2
populations derived from a reciprocal cross between very closely related Virginia
type peanut cultivars with spreading and bunch growth habits were examined. The
spreading/bunch trait was shown to be controlled by a single gene with no
cytoplasmic effect. That gene was named Bunch1 and was significantly correlated
with pod yield per plant, time to maturation and the ratio of "dead-end" pods.
Subsequently, bulked segregant analysis was performed on 52 completely bunch, and
47 completely spreading F3 families. In order to facilitate the process of SNP
detection and candidate-gene analysis, the transcriptome was used instead of
genomic DNA. Young leaves were sampled and bulked. Reads from Illumina sequencing
were aligned against the peanut reference transcriptome and the diploid genomes.
Inter-varietal SNPs were detected, scored and quality-filtered. Thirty-four
candidate SNPs were found to have a bulk frequency ratio value >10 and 6 of those
SNPs were found to be located in the genomic region of linkage group B5. Three
best hits from that over-represented region were further analyzed in the
segregating population. The trait locus was found to be located in a ~1.1 Mbp
segment between markers M875 (B5:145,553,897; 1.9 cM) and M255 (B5:146,649,943;
2.25 cM). The method was validated using a population of recombinant inbreed
lines of the same cross and a new DNA SNP-array. This study demonstrates the
relatively straight-forward utilization of bulk segregant analysis for trait fine
mapping in the low polymeric and heterozygous germplasm of cultivated peanut and
provides a baseline for candidate gene discovery and map-based cloning of Bunch1.
PMID- 28421099
TI - Progress in High-Amylose Cereal Crops through Inactivation of Starch Branching
Enzymes.
AB - High-amylose cereal starches provide many health benefits for humans. The
inhibition or mutation of starch branching enzyme (SBE) genes is an effective
method to develop high-amylose cereal crops. This review summarizes the
development of high-amylose cereal crops through the inactivation of one or more
SBE isoforms or combination with other genes. This review also reveals the causes
of increase in amylose content in high-amylose crops. A series of changes,
including amylopectin structure, crystalline structure, thermal properties, and
hydrolysis properties, occurs as amylose content increases. The different
morphological starch granules nominated as heterogeneous starch granules or
differently stained starch granules are detected in high-amylose cereal crops.
Detailed studies on four heterogeneous starch granules in high-amylose rice,
which is developed by antisense RNA inhibition of SBEI/IIb, indicate that
granules with different morphologies possess various molecular structures and
physicochemical and functional properties. This variation diversifies their
applications in food and non-food industries. However, current knowledge
regarding how these heterogeneous starch granules form and why they exhibit
regional distribution in endosperm remain largely unknown.
PMID- 28421100
TI - Integrated Approach of Agri-nanotechnology: Challenges and Future Trends.
AB - Nanotechnology representing a new frontier in modern agriculture is anticipated
to become a major thrust in near future by offering potential applications. This
integrating approach, i.e., agri-nanotechnology has great potential to cope with
global challenges of food production/security, sustainability and climate change.
However, despite the potential benefits of nanotechnology in agriculture so far,
their relevance has not reached up to the field conditions. The elevating
concerns about fate, transport, bioavailability, nanoparticles toxicity and
inappropriateness of regulatory framework limit the complete acceptance and
inclination to adopt nanotechnologies in agricultural sector. Moreover, the
current research trends lack realistic approach that fail to attain comprehensive
knowledge of risk assessment factors and further toxicity of nanoparticles toward
agroecosystem components viz. plant, soil, soil microbiomes after their release
into the environment. Hence in the present review we attempt to suggest certain
key points to be addressed in the current and future agri-nanotechnology
researches on the basis of recognized knowledge gaps with strong recommendation
of incorporating biosynthesized nanoparticles to carry out analogous functions.
In this perspective, the major points are as follows: (i) Mitigating risk
assessment factors (responsible for fate, transport, behavior, bioavailability
and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii)
Optimizing permissible level of nanoparticles dose within the safety limits by
performing dose dependent studies. (iii) Adopting realistic approach by designing
the experiments in natural habitat and avoiding in vitro assays for accurate
interpretation. (iv) Most importantly, translating environmental friendly and non
toxic biosynthesized nanoparticles from laboratory to field conditions for
agricultural benefits.
PMID- 28421101
TI - Hyperspectral Technologies for Assessing Seed Germination and Trifloxysulfuron
methyl Response in Amaranthus palmeri (Palmer Amaranth).
AB - Weed infestations in agricultural systems constitute a serious challenge to
agricultural sustainability and food security worldwide. Amaranthus palmeri S.
Watson (Palmer amaranth) is one of the most noxious weeds causing significant
yield reductions in various crops. The ability to estimate seed viability and
herbicide susceptibility is a key factor in the development of a long-term
management strategy, particularly since the misuse of herbicides is driving the
evolution of herbicide response in various weed species. The limitations of most
herbicide response studies are that they are conducted retrospectively and that
they use in vitro destructive methods. Development of a non-destructive method
for the prediction of herbicide response could vastly improve the efficacy of
herbicide applications and potentially delay the evolution of herbicide
resistance. Here, we propose a toolbox based on hyperspectral technologies and
data analyses aimed to predict A. palmeri seed germination and response to the
herbicide trifloxysulfuron-methyl. Complementary measurement of leaf
physiological parameters, namely, photosynthetic rate, stomatal conductence and
photosystem II efficiency, was performed to support the spectral analysis. Plant
response to the herbicide was compared to image analysis estimates using mean
gray value and area fraction variables. Hyperspectral reflectance profiles were
used to determine seed germination and to classify herbicide response through
examination of plant leaves. Using hyperspectral data, we have successfully
distinguished between germinating and non-germinating seeds, hyperspectral
classification of seeds showed accuracy of 81.9 and 76.4%, respectively.
Sensitive and resistant plants were identified with high degrees of accuracy
(88.5 and 90.9%, respectively) from leaf hyperspectral reflectance profiles
acquired prior to herbicide application. A correlation between leaf physiological
parameters and herbicide response (sensitivity/resistance) was also demonstrated.
We demonstrated that hyperspectral reflectance analyses can provide reliable
information about seed germination and levels of susceptibility in A. palmeri.
The use of reflectance-based analyses can help to better understand the
invasiveness of A. palmeri, and thus facilitate the development of targeted
control methods. It also has enormous potential for impacting environmental
management in that it can be used to prevent ineffective herbicide applications.
It also has potential for use in mapping tempo-spatial population dynamics in
agro-ecological landscapes.
PMID- 28421103
TI - SVP-like MADS Box Genes Control Dormancy and Budbreak in Apple.
AB - The annual growth cycle of trees is the result of seasonal cues. The onset of
winter triggers an endodormant state preventing bud growth and, once a chilling
requirement is satisfied, these buds enter an ecodormant state and resume
growing. MADS-box genes with similarity to Arabidopsis SHORT VEGETATIVE PHASE
(SVP) [the SVP-like and DORMANCY ASSOCIATED MADS-BOX (DAM) genes] have been
implicated in regulating flowering and growth-dormancy cycles in perennials.
Here, we identified and characterized three DAM-like (MdDAMs) and two SHORT
VEGETATIVE PHASE-like (MdSVPs) genes from apple (Malus * domestica 'Royal Gala').
The expression of MdDAMa and MdDAMc indicated they may play a role in triggering
autumn growth cessation. In contrast, the expression of MdDAMb, MdSVPa and MdSVPb
suggested a role in maintaining bud dormancy. Consistent with this, ectopic
expression of MdDAMb and MdSVPa in 'Royal Gala' apple plants resulted in delayed
budbreak and architecture change due to constrained lateral shoot outgrowth, but
normal flower and fruit development. The association of MdSVPa and MdSVPb
expression with floral bud development in the low fruiting 'Off' trees of a
biennial bearing cultivar 'Sciros' suggested the SVP genes might also play a role
in floral meristem identity.
PMID- 28421102
TI - Ethylene Role in Plant Growth, Development and Senescence: Interaction with Other
Phytohormones.
AB - The complex juvenile/maturity transition during a plant's life cycle includes
growth, reproduction, and senescence of its fundamental organs: leaves, flowers,
and fruits. Growth and senescence of leaves, flowers, and fruits involve several
genetic networks where the phytohormone ethylene plays a key role, together with
other hormones, integrating different signals and allowing the onset of
conditions favorable for stage progression, reproductive success and organ
longevity. Changes in ethylene level, its perception, and the hormonal crosstalk
directly or indirectly regulate the lifespan of plants. The present review
focused on ethylene's role in the development and senescence processes in leaves,
flowers and fruits, paying special attention to the complex networks of ethylene
crosstalk with other hormones. Moreover, aspects with limited information have
been highlighted for future research, extending our understanding on the
importance of ethylene during growth and senescence and boosting future research
with the aim to improve the qualitative and quantitative traits of crops.
PMID- 28421104
TI - Evolving Tale of TCPs: New Paradigms and Old Lacunae.
AB - Teosinte Branched1/Cycloidea/Proliferating cell factors (TCP) genes are key
mediators of genetic innovations underlying morphological novelties, stress
adaptation, and evolution of immune response in plants. They have a remarkable
ability to integrate and translate diverse endogenous, and environmental signals
with high fidelity. Compilation of studies, aimed at elucidating the mechanism of
TCP functions, shows that it takes an amalgamation and interplay of several
different factors, regulatory processes and pathways, instead of individual
components, to achieve the incredible functional diversity and specificity,
demonstrated by TCP proteins. Through this minireview, we provide a brief
description of key structural features and molecular components, known so far,
that operate this conglomerate, and highlight the important conceptual challenges
and lacunae in TCP research.
PMID- 28421105
TI - Nitrate: A Crucial Signal during Lateral Roots Development.
AB - Root plasticity is an important trait for plants to forage nutrient and adapt to
survival in a complicated environment. Lateral roots (LRs) are generally more
sensitive than primary roots in response to changing environmental conditions. As
the main source of nitrogen for most higher plants, nitrate acting as a signal
has received great attention in the regulation of LR development. In general,
there are dual effects including stimulatory and inhibitory of low nitrate on LR
development; while high nitrate supply has an inhibitory effect on LR
development; nitrate heterogeneity also has a stimulatory effect on LR
development in [Formula: see text]- rich zone. Here, we focus on recent
progresses in the role of a nitrate signal in the regulation of the LRs
development.
PMID- 28421106
TI - The Synergistic Responses of Different Photoprotective Pathways in Dwarf Bamboo
(Fargesia rufa) to Drought and Subsequent Rewatering.
AB - : Dwarf bamboo-dominated forests are often subjected to temporary periods of
drought due to rising air temperature and decreasing rainfall. Nevertheless, the
relationship among CO2 assimilation, photoprotective pathways and metabolism of
reactive oxygen species (ROS) remains unexplored in bamboo species. Changes in
leaf gas exchange, chlorophyll fluorescence, energy partitioning, antioxidative
system and compounds related to ROS metabolism in Fargesia rufa plants subjected
to drought and subsequent rewatering were analyzed. Drought resulted in a
reversible inhibition of photochemistry, particularly net CO2 assimilation, and
lipid peroxidation due to ROS accumulation. Meanwhile, photoprotective pathways,
including the water-water cycle (especially for moderate drought), and adjustment
in antenna pigments, thermal dissipation and antioxidative defense capacity at
organelle levels (especially for severe drought), were up-regulated at the stress
phase. Conversely, photorespiration was down-regulated after drought stress. As a
result, rewatering restored most of the photochemical activity under drought,
especially moderate drought. Moreover, thermal dissipation under severe drought
was still operated for avoiding high ROS levels after rewatering. Therefore, the
synergistic function of these photoprotective pathways except photorespiration
can protect the photosynthetic apparatus from oxidative damage in response to
varying intensities of drought stress when CO2 assimilation is restricted. This
is helpful for the gradual recovery of photosynthetic capacity after rewatering.
Thus, F. rufa plants can withstand drought and is capable of survival in such
environment. HIGHLIGHTS: 1. The effects of drought and subsequent rewatering on
Fargesia rufa were studied.2. Drought resulted in a reversible inhibition of
photochemistry.3. Photoprotective pathways except photorespiration were up
regulated at the drought phase.4. Rewatering rapidly restored photochemical
activity, especially under moderate drought.5. Fargesia rufa plant is capable of
resisting and surviving drought environment.
PMID- 28421107
TI - Sexual Dimorphism of miRNAs Secreted by Bovine In vitro-produced Embryos.
AB - Sexual dimorphism of bovine blastocysts has previously been observed through
differences in development, cell death, metabolism, telomere length, DNA
methylation, and transcriptomics. However, dimorphism in the secretion of miRNAs
to culture media has not yet been evaluated. The objectives of this study were to
determine if sex-specific blastocyst miRNA secretion occurs and to further
investigate the role these miRNAs may have in the interaction between a
blastocyst and the maternal environment. In vitro embryo culture was performed
and media from male and female blastocysts was collected into sex-specific pools.
Profiling of 68 miRNAs revealed a total of eight miRNAs that were differentially
expressed between female and male-conditioned media. Validation by qPCR confirmed
higher expression of miR-22 (P < 0.05), miR-122 (P < 0.05), and miR-320a (P <
0.05) in female media for three additional biological replicates. To examine the
potential roles of secreted miRNAs to the media in communication with the
maternal environment, miR-22, miR-122, and miR-320a were each supplemented to
four replicates of primary bovine endometrial epithelial cell culture. Uptake of
miR-122 (P < 0.05) and miR-320a (P < 0.05) was detected, and a trend of uptake
was detected for miR-22 (P > 0.05). Further, expression of the progesterone
receptor transcript, a predicted target of all three miRNAs, was found to be
upregulated in the cells following supplementation of miR-122 (P < 0.05) and miR
320a (P < 0.05), and a trend upregulation of the transcript was observed
following miR-22 (P > 0.05) supplementation. This work demonstrates that male and
female conceptuses are able to differentially secrete miRNAs at the blastocyst
stage and that these miRNAs have the ability to induce a transcriptomic response
when applied to maternal cells. This knowledge builds on the known dimorphic
differences in conceptuses at the blastocyst stage and demonstrates a role for
blastocyst-secreted miRNAs in cell-cell communication.
PMID- 28421108
TI - The Effect of Hepatosteatosis on Response to Antiviral Treatment in Patients with
Chronic Hepatitis B: A Meta-Analysis.
AB - Background. This study is to systematically analyze the effects of
hepatosteatosis on the response to antiviral treatment in patients with chronic
hepatitis B (CHB) and hepatosteatosis. Methods. Systematic search was performed
in PubMed, Embase, Web of Science, Elsevier, and the Chinese BioMedical
literature databases for relevant studies published until February 2016.
Treatment outcomes were compared between patients with CHB plus concomitant
hepatosteatosis and those without hepatosteatosis. Results. A total of 8
prospective cohort studies (399 patients with CHB plus hepatosteatosis and 688
patients with only CHB) were included. Biochemical and virological response at
both 48 and 96 weeks were significantly lower in patients with CHB plus
hepatosteatosis as compared to that in patients with only CHB. Subgroup analysis
based on methods used for diagnosis of hepatosteatosis and treatment regimens
showed that when hepatosteatosis was diagnosed on Doppler ultrasound and treated
with nucleotide analogues, patients with CHB plus hepatosteatosis showed lower
biochemical (62.7% versus 75.8%, P = 0.002) and virological response (66.2%
versus 72.3%, P = 0.006) as compared to that in patients with CHB. Conclusion.
Hepatosteatosis lowers the efficacy of antiviral treatment in patients with CHB,
especially when hepatosteatosis was diagnosed on ultrasound findings and treated
with nucleotide analogues.
PMID- 28421109
TI - Bleeding Meckel's Diverticulum in Children: The Diagnostic Value of Double
Balloon Enteroscopy.
AB - Background. Meckel's diverticulum (MD) is the most common congenital anomaly of
the gastrointestinal tract. The purpose of this study was to evaluate the
diagnostic value and safety of double-balloon enteroscopy (DBE) for bleeding MD
in children. Methods. We included consecutive children who were highly suspected
of MD between 2012 and 2013. All patients underwent Meckel's scan. DBE was
performed for patient with negative Meckel's scan. An exploratory laparoscopy was
performed in children with positive Meckel's scan or DBE. Results. 42 patients
met the inclusion criteria. 40 patients were confirmed to have MD by exploratory
laparoscopy. Meckel's scan was positive in 36 and negative in 6, with 34 as true
positives and 2 as false positives. Six patients with negative Meckel's scan were
found to have MD by retrograde DBE and had immediate operation. The distance from
the diverticulum to the ileocecal valve was 40 to 60 cm. Ectopic gastric mucosa
was present in all 6 patients (100%). After operation, patients were followed in
clinic for 20 to 42 months and no evidence of GI bleeding or recurrent anemia was
observed. Conclusions. Double-balloon enteroscopy can be a reliable diagnostic
tool for bleeding Meckel's diverticulum in children with negative Meckel's scan.
PMID- 28421110
TI - Prognostic Evaluation of Vimentin Expression in Correlation with Ki67 and CD44 in
Surgically Resected Pancreatic Ductal Adenocarcinoma.
AB - Purpose. Radical surgical resection with adjuvant chemotherapy or chemo
radiotherapy is the most effective treatment for pancreatic ductal adenocarcinoma
(PDAC). However, relatively few studies investigate the prognostic significance
of biological markers in PDAC. This study aims to look into the expressions of
vimentin, Ki67, and CD44 in PDAC surgical specimens and their potential
prognostic implications in survival. Method. The study was designed as
retrospective, and vimentin, Ki67, and CD44 expressions were evaluated by
immunohistochemistry in 53 pancreatic ductal adenocarcinoma cases. Overall
survival was assessed by the Kaplan-Meier method. Results. Patients' median age
was 68 years. The median survival was 18 months. The tumors were T3-4 in 40/53
(75.5%), and metastases in lymph nodes were found in 42 out of 53 (79.2%) cases.
On multivariate analysis, the size of primary tumor (p < 0.001), the surgical
resection margin status (p = 0.042), and vimentin expression (p = 0.011) were
independently correlated with overall survival. Conclusions. Long-term survival
after resection of PDAC is still about 15%. Vimentin expression is a potential
independent adverse prognostic molecular marker and should be included in
histopathological reports. Also, CD44 expression correlates with high Ki67,
vimentin positivity, and N stage and may represent a potential target of novel
therapeutic modalities in pancreatic adenocarcinoma patients.
PMID- 28421111
TI - XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T Gene Polymorphisms Associated with
Male Infertility Risk: Evidences from Case-Control and In Silico Studies.
AB - We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6
61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men
including 178 infertile males (102 idiopathic azoospermia and 76 severe
oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7
6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by
PCR. The 2R allele and 2R allele carriers of XRCC5 VNTR polymorphism
significantly decreased risk of male infertility. The mutant GG genotypes and
carriers of the CG and GG genotypes of XRCC6 -61C>G showed increased risk for the
male infertility. Furthermore, the G allele of the XRCC6 -61C>G was correlated
with increased susceptibility to male infertility. Likewise, the T allele of the
XRCC7 6721G>T polymorphism was associated with increased susceptibility to male
infertility in azoospermia. In silico analysis predicted that the presence of
tandem repeats in XRCC5 gene prompter can be sequence to bind to more nuclear
factors. Also, rs2267437 (C>G) variant was located in a well-conserved region in
XRCC6 promoter and this variation might lead to differential allelic expression.
The XRCC7 6721G>T gene polymorphism occurred in an acceptor-splicing site, but
this polymorphism has no severe modification on XRCC7 mRNA splicing. Our results
indicate the association of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T gene
polymorphisms with male infertility in Iranian men.
PMID- 28421112
TI - Self-Monitoring of Blood Glucose to Assess Dawn Phenomenon in Chinese People with
Type 2 Diabetes Mellitus.
AB - Aims. We investigated whether self-monitoring of blood glucose could be used to
assess dawn phenomenon in Chinese people with type 2 diabetes mellitus (T2DM).
Methods. A total of 306 people with T2DM underwent continuous glucose monitoring
and self-monitoring of blood glucose for 72 h. A linear model was used to fit the
optimal linear formula of the magnitude of dawn phenomenon (DeltaDawn) and self
monitoring of blood glucose values. Results. The prevalence of dawn phenomenon
was similar within different oral antidiabetic drug groups (42.5%, 31.5%, and
40.9%, P = 0.216). Multiple variable linear regression showed that prebreakfast,
prelunch, and predinner glucose measurements were independently and significantly
correlated with DeltaDawn. The linear formula between DeltaDawn and blood glucose
was as follows: DeltaDawn (mg/dL) = 0.557 * prebreakfast - 0.065 * prelunch -
0.164 * predinner - 20.894 (mg/dL) (adjusted R2 = 0.302, P = 0.000). Conclusions.
Dawn phenomenon could be partly assessed by blood glucose self-monitoring in
Chinese people with T2DM using the abovementioned formula. The incidence of dawn
phenomenon was similar among patients in different oral antidiabetic drug groups.
PMID- 28421113
TI - Chronic Hyperinsulinaemic Hypoglycaemia in Rats Is Accompanied by Increased Body
Weight, Hyperleptinaemia, and Decreased Neuronal Glucose Transporter Levels in
the Brain.
AB - The brain is vulnerable to hypoglycaemia due to a continuous need of energy
substrates to meet its high metabolic demands. Studies have shown that severe
acute insulin-induced hypoglycaemia results in oxidative stress in the rat brain,
when neuroglycopenia cannot be evaded despite increased levels of cerebral
glucose transporters. Compensatory measures in the brain during chronic insulin
induced hypoglycaemia are less well understood. The present study investigated
how the brain of nondiabetic rats copes with chronic insulin-induced
hypoglycaemia for up to eight weeks. Brain level of different substrate
transporters and redox homeostasis was evaluated. Hyperinsulinaemia for 8 weeks
consistently lowered blood glucose levels by 30-50% (4-6 mM versus 7-9 mM in
controls). The animals had increased food consumption, body weights, and
hyperleptinaemia. During infusion, protein levels of the brain neuronal glucose
transporter were decreased, whereas levels of lipid peroxidation products were
unchanged. Discontinued infusion was followed by transient systemic
hyperglycaemia and decreased food consumption and body weight. After 4 weeks,
plasma levels of lipid peroxidation products were increased, possibly as a
consequence of hyperglycaemia-induced oxidative stress. The present data suggests
that chronic moderate hyperinsulinaemic hypoglycaemia causes increased body
weight and hyperleptinaemia. This is accompanied by decreased neuronal glucose
transporter levels, which may be leptin-induced.
PMID- 28421115
TI - Radix Entomolaris in the Mandibular Molar Teeth of an Iranian Population.
AB - Purpose. Supernumerary roots in permanent mandibular molar teeth make endodontic
treatment more complicated. The aim of this study was to determine the prevalence
of Radix Entomolaris (RE) in permanent mandibular first and second molars in the
population of Kerman, in the southeast of Iran. Materials and Methods. From a
collection of 500 mandibular first and second molar teeth extracted over 2015
2016 at dental clinics in Kerman, teeth were scored for an additional
distolingual root, and the average root length and root morphology of this extra
root were determined using the De Moor classification scheme. Results. In this
population, RE occurred in 6% of mandibular first molars (4% with a straight apex
(Type I) and 2% with buccal apical curvature (Type III)). In all cases, RE was
the shortest root, with an average root length of 18.37 mm. RE occurred in only
0.8% of mandibular second molars, with an average root length of 18.0 mm. All
mandibular second molars with RE were of Type III. Fisher's exact test showed
that the difference in frequency between first and second molars was
statistically significant (two-sided P = 0.002). Conclusion. Radix Entomolaris
occurs more frequently in mandibular first molars than in mandibular second
molars in this sample of 500 mandibular molars. The reported rate of 6% in first
molars is expected to be higher than reported rates in European or Caucasian
populations where the prevalence is typically less than 2%.
PMID- 28421116
TI - Mitochondrial Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes.
AB - Human pluripotent stem cells derived cardiomyocytes (PSC-CMs) have been widely
used for disease modeling, drug safety screening, and preclinical cell therapy to
regenerate myocardium. Most studies have utilized PSC-CM grown in vitro for a
relatively short period after differentiation. These PSC-CMs demonstrated
structural, electrophysiological, and mechanical features of primitive
cardiomyocytes. A few studies have extended in vitro PSC-CM culture time and
reported improved maturation of structural and electromechanical properties. The
degree of mitochondrial maturation, however, remains unclear. This study
characterized the development of mitochondria during prolonged in vitro culture.
PSC-CM demonstrated an improved mitochondrial maturation with prolonged culture,
in terms of increased mitochondrial relative abundance, enhanced membrane
potential, and increased activity of several mitochondrial respiratory complexes.
These are in parallel with the maturation of other cellular components. However,
the maturation of mitochondria in PSC-CMs grown for extended in vitro culture
exhibits suboptimal maturation when compared with the maturation of mitochondria
observed in the human fetal heart during similar time interval.
PMID- 28421114
TI - Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric
Cancer.
AB - Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection
causes mononucleosis, Burkett's lymphoma, nasopharyngeal carcinoma, autoimmune
diseases, and gastric cancer (GC). The persistent infection causes malignancies
in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with
chronic inflammation. This chronic inflammation is thought to be the cause of
genomic instability. About 45%-word population have a probability of having both
pathogens, namely, H. pylori and EBV. Approximately 180 per hundred thousand
population is developing GC along with many gastric abnormalities. This makes GC
the third leading cause of cancer-related death worldwide. Although lots of
research are carried out individually for EBV and H. pylori, still there are very
few reports available on coinfection of both pathogens. Recent studies suggested
that EBV and H. pylori coinfection increases the occurrence of GC as well as the
early age of GC detection comparing to individual infection. The aim of this
review is to present status on coinfection of both pathogens and their
association with GC.
PMID- 28421117
TI - Chronic Pain in Children: A Look at the Referral Process to a Pediatric Pain
Clinic.
AB - We reviewed the referral pattern of children with chronic pain to a specialized
pediatric pain clinic. Data were obtained from referring physicians and medical
records and during an interview with patients and their parents by physicians and
a psychologist. We analyzed the following: referral diagnosis, demographics,
duration of symptoms, number of physicians previously consulted, school
attendance, sports activities, presence of psychological disorders, final team
diagnosis, and outcomes. Children had been experiencing pain for 34 +/- 55
months. Patients had consulted on average 3 physicians in addition to their
pediatrician. 32% of the patients had missed at least 10 days of school in a
calendar year, and 47% had stopped playing sports. 15% had an operation because
of pain that had been unsuccessful. The most common missed diagnosis was anxiety
(25%) and depression (13%). 69% of the patients were back to school and/or
playing sports within 4 months from our initial consultation. 32% of the patients
did not make any progress during the follow-up period. The most common reasons
for failure to improve were no compliance with the recommended treatments and
poorly controlled major mood disorder. The time to refer children with chronic
pain for specialized care could be extremely long causing significant social and
psychological consequence.
PMID- 28421118
TI - Pattern of Traditional Medicine Utilization among HIV/AIDS Patients on
Antiretroviral Therapy at a University Hospital in Northwestern Ethiopia: A Cross
Sectional Study.
AB - The objective of this study was to assess traditional, complementary, and
alternative medicine (TCAM) utilization pattern among HIV/AIDS patients on
antiretroviral therapy at University of Gondar Comprehensive Specialized
Hospital. Materials and Methods. Data on sociodemographic profile and clinical
and TCAM utilization were collected using a structured, pretested questionnaire
from April 01 to May 28, 2014, through interviews with patients. Data on CD4
count, HIV stage, and ART regimen were collected from patient records. Analysis
was conducted descriptively using SPSS version 20. Results. Of the 300
participants, 43.7% reported using TCAM, with the largest proportion of them from
religious institutions (churches/mosques) (41.22%), followed by home prepared
(32.82%) and traditional healers (16.03%). The leading forms of TCAM used were
spiritual and herbal therapies constituting 56.49% and 36.64% of the patients,
respectively. The most frequently used herbal products included Nigella sativa
(22.92%) and Moringa oleifera (20.83%). Most of the patients (73.30%) using TCAM
reported improvement in their conditions. Conclusions. TCAM utilization among
HIV/AIDS patients on ART was common and different sources and types were used
alongside ART, with improvement reported by most. Further research is needed to
identify CAM therapies which may be used as adjunct treatments among these
patients.
PMID- 28421119
TI - Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula,
on the Main CYP450 Activities in Rats Using a Cocktail Method.
AB - The purpose of this work was to study the influences of Realgar-Indigo naturalis
(RIF) and its principal element realgar on 4 main cytochrome P450 enzymes
activities in rats. A simple and efficient cocktail method was developed to
detect the four probe drugs simultaneously. In this study, Wistar rats were
administered intragastric RIF and realgar for 14 days; mixed probe drugs were
injected into rats by caudal vein. Through analyzing the pharmacokinetic
parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The
results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11
enzyme activity significantly. Interestingly, in realgar high dosage group,
CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of
realgar manifested a good dose-dependent manner. The RIF results indicated that
drug coadministrated with RIF may need to be paid attention in relation to drug
drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM),
does have curative effect on acute promyelocytic leukemia (APL). Its toxicity
studies should be focused on. We found that, in realgar high dosage group,
CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its
potential toxicity mechanism.
PMID- 28421120
TI - In Vitro and In Vivo Studies on Quercus acuta Thunb. (Fagaceae) Extract: Active
Constituents, Serum Uric Acid Suppression, and Xanthine Oxidase Inhibitory
Activity.
AB - Quercus acuta Thunb. (Fagaceae) (QA) is cultivated as a dietary and ornamental
plant in China, Japan, South Korea, and Taiwan. It has been widely used as the
main ingredient of acorn tofu, a traditional food in China and South Korea. The
aim of this study was to determine in vitro and in vivo xanthine oxidase (XO)
inhibitory and antihyperuricemic activities of an ethyl acetate extract of QA
leaf (QALE) and identify its active phytochemicals using gas chromatography-mass
spectrometry (GC-MS) and liquid chromatography (LC) systems. The QALE was found
to possess potent in vitro antioxidant and XO inhibitory activities. In vivo
study using hyperuricemic mice induced with potassium oxonate demonstrated that
the QALE could inhibit hepatic XO activity at a relatively low oral dose (50
mg/kg) and significantly alleviate hyperuricemia to a similar extent as
allopurinol. Several active compounds including vitamin E known to possess XO
inhibitory activity were identified from the QALE. To the best of our knowledge,
this is the first study that reports the active constituents and
antihyperuricemic effect of QA, suggesting that it is feasible to use QALE as a
food therapy or alternative medicine for alleviating hyperuricemia and gout.
PMID- 28421121
TI - Availability, Pharmaceutics, Security, Pharmacokinetics, and Pharmacological
Activities of Patchouli Alcohol.
AB - Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical
bioactive ingredients and is mainly isolated from aerial part of Pogostemon
cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has
been widely applied in perfume industries. This review was written with the use
of reliable information published between 1974 and 2016 from libraries and
electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect,
Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of
security, pharmacokinetics, and bioactivities of PA and at further providing a
potential guide in exploring the PA and its use in various medical fields. We
found that PA maybe was a low toxic drug that was acquired numerously through
vegetable oil isolation and chemical synthesis and its stability and low water
dissolution were improved in pharmaceutics. It also possessed specific
pharmacokinetic characteristics, such as two-compartment open model, first-order
kinetic elimination, and certain biometabolism and biotransformation process, and
was shown to have multiple biological activities, that is, immunomodulatory, anti
inflammatory, antioxidative, antitumor, antimicrobial, insecticidal,
antiatherogenic, antiemetic, whitening, and sedative activity. However, the
systematic evaluations of preparation, pharmaceutics, toxicology,
pharmacokinetics, and bioactivities underlying molecular mechanisms of action
also required further investigation prior to practices of PA in clinic.
PMID- 28421123
TI - Study of the Hypoglycemic Activity of Derivatives of Isoflavones from Cicer
arietinum L.
AB - The chickpea, a food and medicine used by the people of Xinjiang, has a
beneficial hypoglycemic effect. To better utilize this national resource and
develop hypoglycemic agents from components of the chickpea, a series of new
derivatives of isoflavone compounds from the chickpea were synthesized. An
insulin-resistant (IR) HepG2 cell model was used to screen the hypoglycemic
activities of these compounds. And the structure-activity relationships of these
compounds were explored. Additionally, several combinations of these compound
displayed higher hypoglycemic activity than any single compound, and they had
similar hypoglycemic activity to that of the positive control group (p > 0.05).
In addition, combination 3 and combination 6 exerted different effects on the
insulin sensitivity of H4IIE cells stimulated with resistin. And the results
indicated that combination 3 would have higher hypoglycemic activity. These
findings demonstrate the characteristics of multiple components and targets of
Chinese herbal medicine. This evidence may provide new ideas for the development
of hypoglycemic drugs.
PMID- 28421122
TI - Potential Antitumor Activity and Apoptosis Induction of Glossostemon bruguieri
Root Extract against Hepatocellular Carcinoma Cells.
AB - Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This
study was performed to investigate the antiproliferative effects of moghat root
extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC)
cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked
immunosorbent assay, caspase and apoptotic activation, flow cytometry, and
immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 +/- 6 MUg/ml)
and for Hep3B (1510 +/- 5 MUg/ml) induced significant growth-inhibitory effects
against HCC cells, with no cytotoxic effect on normal hepatocytes. MRE treatment
induced apoptotic effects to HepG2 cells in a caspase-dependent manner and via
upregulating p53/p21 and PCNA. The upregulation of p21 was controlled by p53
expression in HepG2 but not in Hep3B despite upregulation of Bax protein in both
cell lines. Interestingly, p21 may be a remarkable switch to G1 arrest in HepG2
cells, but not in Hep3B cells. In addition, Fas- and mitochondria-mediated
pathways were found to be involved in MRE-induced apoptosis in Hep3B cells. The
GC-MS analysis of MRE revealed two major constituents of pharmaceutical
importance: the flavonoid apigenin (17.04%) and the terpenoid squalene (11.32%).
The data presented in this paper introduces G. bruguieri as a promising nontoxic
herb with therapeutic potential for HCC. To the authors' knowledge, the present
study provides the first report on the anticancer activity of MRE on HCC cells.
PMID- 28421124
TI - Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial
Dysfunction in Chronic Aristolochic Acid Nephropathy.
AB - Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD)
on chronic aristolochic acid nephropathy (AAN) in mice and its underlying
mechanisms were studied. Methods. Mice were randomly divided into the following
six groups: the control group, the model group (AAN), the saline-treated group
(AAN + vehicle), the normal dose DFD-treated group (AAN + NDFD), the high dose
DFD-treated group (AAN + HDFD), and the rosiglitazone treated group (AAN + Rosi).
After treating for 8 weeks, 24 h urine and blood samples were collected and the
mice sacrificed to study the biochemical parameters associated with renal
function. The samples were analyzed for renal fibrosis and mitochondrial
dysfunction (MtD) markers. To achieve that, collagen III, collagen I,
mitochondrial DNA copy numbers (mtDNA), mitochondrial membrane potential (MMP),
ATP content, and ROS production were evaluated. Results. Our results showed that
proteinuria, kidney function, and the renal pathological characteristics were
improved by DFD and rosiglitazone. The expression of collagen III and collagen I
decreased after treating with either DFD or rosiglitazone. Mitochondrial
dysfunction based on the increase in ROS production, decrease in mitochondrial
DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and
rosiglitazone. Conclusions. DFD could protect against renal impairments and
ameliorate mitochondrial dysfunction in chronic AAN mice.
PMID- 28421125
TI - Automatic Microaneurysms Detection Based on Multifeature Fusion Dictionary
Learning.
AB - Recently, microaneurysm (MA) detection has attracted a lot of attention in the
medical image processing community. Since MAs can be seen as the earliest lesions
in diabetic retinopathy, their detection plays a critical role in diabetic
retinopathy diagnosis. In this paper, we propose a novel MA detection approach
named multifeature fusion dictionary learning (MFFDL). The proposed method
consists of four steps: preprocessing, candidate extraction, multifeature
dictionary learning, and classification. The novelty of our proposed approach
lies in incorporating the semantic relationships among multifeatures and
dictionary learning into a unified framework for automatic detection of MAs. We
evaluate the proposed algorithm by comparing it with the state-of-the-art
approaches and the experimental results validate the effectiveness of our
algorithm.
PMID- 28421126
TI - Femoral Neck Strain during Maximal Contraction of Isolated Hip-Spanning Muscle
Groups.
AB - The aim of the study was to investigate femoral neck strain during maximal
isometric contraction of the hip-spanning muscles. The musculoskeletal and the
femur finite-element models from an elderly white woman were taken from earlier
studies. The hip-spanning muscles were grouped by function in six hip-spanning
muscle groups. The peak hip and knee moments in the model were matched to
corresponding published measurements of the hip and knee moments during maximal
isometric exercises about the hip and the knee in elderly participants. The
femoral neck strain was calculated using full activation of the agonist muscles
at fourteen physiological joint angles. The 5% +/- 0.8% of the femoral neck
volume exceeded the 90th percentile of the strain distribution across the 84
studied scenarios. Hip extensors, flexors, and abductors generated the highest
tension in the proximal neck (2727 MUepsilon), tension (986 MUepsilon) and
compression (-2818 MUepsilon) in the anterior and posterior neck, and compression
(-2069 MUepsilon) in the distal neck, respectively. Hip extensors and flexors
generated the highest neck strain per unit of joint moment (63-67 MUepsilon.m.N
1) at extreme hip angles. Therefore, femoral neck strain is heterogeneous and
muscle contraction and posture dependent.
PMID- 28421127
TI - Using Agent-Based Models to Develop Public Policy about Food Behaviours: Future
Directions and Recommendations.
AB - Most adults are overweight or obese in many western countries. Several population
level interventions on the physical, economical, political, or sociocultural
environment have thus attempted to achieve a healthier weight. These
interventions have involved different weight-related behaviours, such as food
behaviours. Agent-based models (ABMs) have the potential to help policymakers
evaluate food behaviour interventions from a systems perspective. However, fully
realizing this potential involves a complex procedure starting with obtaining and
analyzing data to populate the model and eventually identifying more efficient
cross-sectoral policies. Current procedures for ABMs of food behaviours are
mostly rooted in one technique, often ignore the food environment beyond home and
work, and underutilize rich datasets. In this paper, we address some of these
limitations to better support policymakers through two contributions. First, via
a scoping review, we highlight readily available datasets and techniques to deal
with these limitations independently. Second, we propose a three steps' process
to tackle all limitations together and discuss its use to develop future models
for food behaviours. We acknowledge that this integrated process is a leap
forward in ABMs. However, this long-term objective is well-worth addressing as it
can generate robust findings to effectively inform the design of food behaviour
interventions.
PMID- 28421128
TI - A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme
Cystathionine beta-Synthase: Increased CO Reactivity as a Novel Molecular
Mechanism of Pathogenicity?
AB - The human disease classical homocystinuria results from mutations in the gene
encoding the pyridoxal 5'-phosphate- (PLP-) dependent cystathionine beta-synthase
(CBS), a key enzyme in the transsulfuration pathway that controls homocysteine
levels, and is a major source of the signaling molecule hydrogen sulfide (H2S).
CBS activity, contributing to cellular redox homeostasis, is positively regulated
by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO* binding to
a noncatalytic heme moiety. Despite extensive studies, the molecular basis of
several pathogenic CBS mutations is not yet fully understood. Here we found that
the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral
properties and markedly increased affinity for CO, making the protein much more
prone than wild type (WT) CBS to inactivation at physiological CO levels. The
higher CO affinity could result from the slightly higher flexibility in the heme
surroundings revealed by solving at 2.80-A resolution the crystallographic
structure of a truncated p.P49L. Additionally, we report that p.P49L displays
impaired H2S-generating activity, fully rescued by PLP supplementation along the
purification, despite a minor responsiveness to AdoMet. Altogether, the results
highlight how increased propensity to CO inactivation of an otherwise WT-like
variant may represent a novel pathogenic mechanism in classical homocystinuria.
PMID- 28421129
TI - Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the
Heart.
AB - Background. Nitric oxide can successfully compete with oxygen for sites of
electron-transport chain in conditions of myocardial hypoxia. These features may
prevent excessive oxidative stress occurring in cardiomyocytes during sudden
hypoxia-reoxygenation. Aim. To study the action of the potent stable NO donor
dinitrosyl iron complex with glutathione (Oxacom(r)) on the recovery of
myocardial contractile function and Ca2+ transients in cardiomyocytes during
hypoxia-reoxygenation. Results. The isolated rat hearts were subjected to 30 min
hypoxia followed by 30 min reoxygenation. The presence of 30 nM Oxacom in hypoxic
perfusate reduced myocardial contracture and improved recovery of left
ventricular developed pressure partly due to elimination of cardiac arrhythmias.
The same Oxacom concentration limited reactive oxygen species generation in
hypoxic cardiomyocytes and increased the viability of isolated cardiomyocytes
during hypoxia from 12 to 52% and after reoxygenation from 0 to 40%. Oxacom
prevented hypoxia-induced elevation of diastolic Ca2+ level and eliminated Ca2+
transport alterations manifested by slow Ca2+ removal from the sarcoplasm and
delay in cardiomyocyte relaxation. Conclusion. The potent stable NO donor
preserved cardiomyocyte integrity and improved functional recovery at hypoxia
reoxygenation both in the isolated heart and in cardiomyocytes mainly due to
preservation of Ca2+ transport. Oxacom demonstrates potential for
cardioprotection during hypoxia-reoxygenation.
PMID- 28421130
TI - Antiretroviral Therapy Initiation Alters the Redox System of Asymptomatic HIV
Infected Individuals: A Longitudinal Study.
AB - Background. The combination antiretroviral therapy (cART) increases the oxidative
stress in HIV-infected people, which in turn favors the onset and aggravation of
non-AIDS comorbidities, a common situation affecting these individuals. We aimed
to evaluate the influence of cART initiation on oxidative stress parameters. This
is a longitudinal study including 30 asymptomatic patients divided according to
their CD4+ T cell count (G1: <500 cell/mL; G2: >500 cell/mL) before (M0) and
after (M1) cART initiation. We analyzed total antioxidant capacity (TAC), fat
soluble vitamins, malondialdehyde, 8-isoprostane, and DNA damage. Results.
Results showed a decrease in TAC, retinol, alpha-tocopherol, and some
carotenoids, in addition to a significant increase in DNA damage at M1. These
changes were more evident in G2 subjects. Moreover, there was a significant 8
isoprostane increase at M1 in individuals belonging to G1. Conclusion. The
results indicate that cART interfered in the redox system, mainly by reducing the
antioxidant defenses. In addition, patients who had CD4+ T counts higher than 500
cells/mm3 showed more susceptibility to genotoxicity, while patients with less
CD4+ T counts displayed more damage triggered by lipoperoxidation. Considering
the early beginning of cART, its chronic use, and its capacity to alter the redox
status, further long-term studies on larger cohorts are needed to define the best
time to initiate therapy and to investigate new strategies to delay the
development of non-AIDS diseases.
PMID- 28413608
TI - Evidence synthesis and decision modelling to support complex decisions:
stockpiling neuraminidase inhibitors for pandemic influenza usage.
AB - Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a
defence against pandemic influenza is a significant public health policy decision
that must be made despite a lack of conclusive evidence from randomised
controlled trials regarding the effectiveness of NAIs on important clinical end
points such as mortality. The objective of this study was to determine whether
NAIs should be stockpiled for treatment of pandemic influenza on the basis of
current evidence. Methods: A decision model for stockpiling was designed. Data on
previous pandemic influenza epidemiology was combined with data on the
effectiveness of NAIs in reducing mortality obtained from a recent individual
participant meta-analysis using observational data. Evidence synthesis techniques
and a bias modelling method for observational data were used to incorporate the
evidence into the model. The stockpiling decision was modelled for adults (>=16
years old) and the United Kingdom was used as an example. The main outcome was
the expected net benefits of stockpiling in monetary terms. Health benefits were
estimated from deaths averted through stockpiling. Results: After adjusting for
biases in the estimated effectiveness of NAIs, the expected net benefit of
stockpiling in the baseline analysis was L444 million, assuming a willingness to
pay of L20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile
NAIs. There was a greater probability that the stockpile would not be utilised
than utilised. However, the rare but catastrophic losses from a severe pandemic
justified the decision to stockpile. Conclusions: Taking into account the
available epidemiological data and evidence of effectiveness of NAIs in reducing
mortality, including potential biases, a decision maker should stockpile anti
influenza medication in keeping with the postulated decision rule.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in the visualisation of information since
Haeckel's time, phylogenetic visualisation has moved forward remarkably little.
In this brief essay, I give a short review of what I consider to be some recent
major advances, and outline a new kind of phylogenetic visualisation. This new
graphic, the fibre plot, uses the metaphor of sections through a tree to describe
change in a phylogeny. As an animation, I suggest it is a powerful method to help
interpret large phylogenetic hypotheses, although snapshots of it can also be
displayed. As we enter the Anthropocene, I argue there has never been a greater
need to know humanity's true place in the world, as depicted in the tree of life.
PMID- 28413610
TI - Animating and exploring phylogenies with fibre plots.
AB - Despite the progress that has been made in many other aspects of data
visualisation, phylogenies are still represented in much the same way as they
first were by Darwin. In this brief essay, I give a short review of what I
consider to be some recent major advances, and outline a new kind of phylogenetic
visualisation. This new graphic, the fibre plot, uses the metaphor of sections
through a tree to describe change in a phylogeny. I suggest it is a useful tool
in gaining an rapid overview of the timing and scale of diversification in large
phylogenies.
PMID- 28413615
TI - Mean Platelet Volume (MPV) as an indicator of disease activity and severity in
lupus.
AB - Background: Amongst the different clinical and laboratory parameters used to
monitor disease activity in systemic lupus erythematosus (SLE), mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. Fifty
patients were recruited through a consecutive non-probability sampling technique
for this cross-sectional study. On the basis of their SLE disease activity index
(SLEDAI) score of greater or lesser than 5, these 50 participants were divided
into two equal groups respectively;25 patients with active SLE, and another 25
participants with stable, inactive lupus. MPV was measured in each group and
compared using SPSS version 16. MPV was also correlated with SLEDAI and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Pearson's
correlation tests were applied. Sensitivity and specificity of MPV were checked
through ROC analysis. Results: The MPV of patients with active SLE (n=25, mean
[M]=7.12, SD=1.01) was numerically lower than those in the inactive-SLE group
(n=25, M= 10.12, SD=0.97), and this was statistically significant ( P<0.001). MPV
had an inverse relationship with both ESR (r=-0.93, P<0.001) and SLEDAI (r=
0.94, P<0.001). However, there was a strong positive correlation between ESR and
SLEDAI (r=0.95, P<0.001). For MPV, a cutoff value of less than 8.5fl had a
sensitivity of 92% and a specificity of 100% ( P< 0.001). Conclusions: Higher
disease activity in SLE is associated with a correspondingly low MPV.
PMID- 28413615
TI - Mean Platelet Volume (MPV) as an indicator of disease activity and severity in
lupus.
AB - Background: Amongst the different clinical and laboratory parameters used to
monitor disease activity in systemic lupus erythematosus (SLE), mean platelet
volume (MPV) is a novel biomarker. Although MPV has been studied in other
rheumatological conditions like rheumatoid arthritis, its role in adult SLE needs
to be defined, especially in Pakistan. Methods: The aim of this study was to
evaluate the role of MPV as a biomarker of disease activity in SLE. Fifty
patients were recruited through a consecutive non-probability sampling technique
for this cross-sectional study. On the basis of their SLE disease activity index
(SLEDAI) score of greater or lesser than 5, these 50 participants were divided
into two equal groups respectively;25 patients with active SLE, and another 25
participants with stable, inactive lupus. MPV was measured in each group and
compared using SPSS version 16. MPV was also correlated with SLEDAI and
erythrocyte sedimentation rate (ESR). Independent sample t-test and Spearman's
rho and Pearson's correlation tests were applied. Sensitivity and specificity of
MPV were checked through ROC analysis. Results: The MPV of patients with
active SLE (n=25, mean [M]=7.12, SD=1.01) was numerically lower than those in the
inactive-SLE group (n=25, M= 10.12, SD=0.97), and this was statistically
significant ( P<0.001). MPV had an inverse relationship with both ESR (r=-0.93,
P<0.001) and SLEDAI (r s= -0.89, P<0.001). However, there was a strong positive
correlation between ESR and SLEDAI (r s=0.90, P<0.001). For MPV, a cutoff value
of less than 8.5fl had a sensitivity of 92% and a specificity of 100% ( P<
0.001). Conclusions: Higher disease activity in SLE is associated with a
correspondingly low MPV.
PMID- 28421136
TI - Time from pre-eclampsia diagnosis to delivery affects future health prospects of
children.
AB - Background and objectives: Pre-eclampsia often has detrimental health effects for
pregnant women and their fetuses, but whether exposure in the womb has long-term
health-consequences for children as they grow up remains poorly understood. We
assessed overall morbidity of children following exposure to either mild or
severe pre-eclampsia up to 30 years after birth and related disease risks to
duration of exposure, i.e. the time from diagnosis to delivery. Methodology: We
did a registry-based retrospective cohort study in Denmark covering the years
1979-2009, using the separate diagnoses of mild and severe pre-eclampsia and the
duration of exposure as predictor variables for specific and overall risks of
later disease. We analysed 3 537 525 diagnoses for 14 disease groups, accumulated
by 758 524 singleton children, after subdividing deliveries in six gestational
age categories, partialing out effects of eight potentially confounding factors.
Results: Exposure to mild pre-eclampsia appeared to have consistent negative
effects on health later in life, although only a few specific disease cases
remained significant after corrections for multiple testing. Morbidity risks
associated with mild pre-eclampsia were of similar magnitude as those associated
with severe pre-eclampsia. Apart from this overall trend in number of diagnoses
incurred across disease groups, hazard ratios for several disorders also
increased with the duration of exposure, including disorders related to the
metabolic syndrome. Conclusions and implications: Maternal pre-eclampsia has
lasting effects on offspring health and differences between exposure to severe
and mild pre-eclampsia appear to be less than previously assumed. Our results
suggest that it would be prudent to include the long-term health prospects of
children in the complex clinical management of mild pre-eclampsia.
PMID- 28421137
TI - The effect of temperature on development and behaviour of relict leopard frog
tadpoles.
AB - Relict leopard frog (Rana [Lithobates] onca) tadpoles were obtained shortly after
hatching at Gosner stage 25 and raised in aquaria maintained at 15, 20, 25, 30
and 35 degrees C. Development was arrested in the 15 degrees C group, and
survivorship declined to 64% after 191 days. However, 80% of the surviving larvae
remained alive after the temperature was increased to 25 degrees C. Of these, 96%
reached metamorphosis. Survivorship of the 20, 25 and 30 degrees C acclimation
groups was 82, 94 and 66%, respectively, whereas none survived at 35 degrees C.
Time to metamorphosis was significantly shorter for the 25 degrees C group (67 +/
1 days), followed by the 30 degrees C (98 +/- 2 days) and 20 degrees C (264 +/-
7 days) groups. A linear 66 cm thermal gradient was used to identify temperature
ranges selected by tadpoles in the different acclimation groups. Five 10 degrees
C gradients (10-20, 15-25, 20-30, 25-35 and 30-40 degrees C) were used, and time
spent in the cooler, middle and warmer thirds of the gradient was compared for 10
individuals from each acclimation group. In the coolest gradient, tadpoles from
all acclimation groups selected the warmer third (>17 degrees C) of the gradient.
In the warmer gradients, tadpoles from the 20 and 25 degrees C acclimation groups
selected temperatures <29 degrees C, while those from the 30 degrees C
acclimation group selected temperatures <33 degrees C. Maximal burst speed for
all groups was greater at experimental temperatures of 25 than 15 degrees C.
Efforts to reintroduce this species to its historical range should select
habitats where water temperatures between 25 and 30 degrees C are available
during the post-hatching period.
PMID- 28421138
TI - Habitat disturbance results in chronic stress and impaired health status in
forest-dwelling paleotropical bats.
AB - Anthropogenic habitat disturbance is a major threat to biodiversity worldwide.
Yet, before population declines are detectable, individuals may suffer from
chronic stress and impaired immunity in disturbed habitats, making them more
susceptible to pathogens and adverse weather conditions. Here, we tested in a
paleotropical forest with ongoing logging and fragmentation, whether habitat
disturbance influences the body mass and immunity of bats. We measured and
compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios)
and the number of circulating immune cells between several bat species with
different roost types living in recovering areas, actively logged forests, and
fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress
levels were higher in individuals from fragmented habitats compared with
conspecifics from actively logged areas. Foliage-roosting species showed a
reduced body mass and decrease in total white blood cell counts in actively
logged areas and fragmented forests compared with conspecifics living in
recovering habitats. Our study highlights that habitat disturbance may have
species-specific effects on chronic stress and immunity in bats that are
potentially related to the roost type. We identified foliage-roosting species as
particularly sensitive to forest habitat deterioration. These species may face a
heightened extinction risk in the near future if anthropogenic habitat
alterations continue.
PMID- 28421139
TI - Regional Relationship between Macular Retinal Thickness and Corresponding Central
Visual Field Sensitivity in Glaucoma Patients.
AB - Purpose. To investigate the relationship between macular retinal thickness (MRT)
and central visual field sensitivity (VFS) in patients with glaucoma. Methods.
This retrospective study enrolled patients diagnosed with open-angle glaucoma.
All study patients underwent Humphrey 10-2 visual field (VF) test and Spectralis
spectral-domain optical coherence tomography (SD-OCT) exam for MRT measurement.
Results. Sixty-eight eyes of 68 patients were examined. The correlation
coefficients between VFS and MRT were 0.331 (P = 0.006) and 0.491 (P = 0.000) in
the superior and inferior hemispheres, respectively. The average MRT in the eyes
with abnormal 10-2 VF hemifields was significantly thinner than that in the eyes
without abnormal hemifields in both hemispheres (P = 0.005 and 0.000 in the
superior and inferior hemisphere, resp.). The average MRT values with an optimal
sensitivity-specificity balance for discriminating the abnormal VF hemifield from
the normal hemifield were 273.5 MUm and 255.5 MUm in the superior and inferior
hemisphere, respectively. The area under the receiver operating characteristic
curve was 0.701 in the superior hemisphere and 0.784 in the inferior hemisphere
(both P < 0.05). Conclusions. MRT measured through SD-OCT was significantly
correlated with central VFS. Lower MRT values might be a warning sign for central
VF defects in glaucoma patients.
PMID- 28421140
TI - Comparison of Corneal Power and Astigmatism between Simulated Keratometry, True
Net Power, and Total Corneal Refractive Power before and after SMILE Surgery.
AB - Purpose. To compare the mean corneal power (Km) and total astigmatism (Ka)
estimated by three methods: simulated keratometry (simK), true net power (TNP),
and total corneal refractive power (TCRP) before and after femtosecond laser
small incision lenticule extraction (SMILE) surgery. Methods. A retrospective,
cross-sectional study. SimK, TNP, and TCRP from a Scheimpflug analyzer were
obtained from 144 patients before and 6 months after SMILE surgery. Km and Ka
were recorded as the mean of individual paracentral rings of 1.0 to 8.0 mm (R1 to
R8). The surgically induced changes in Km (delta-simK, delta-TNP, and delta-TCRP)
and Ka (delta-simKa, delta-TNPa, and delta-TCRPa) were compared to the changes in
spherical equivalent of the cycloplegic refraction (delta-SE) and astigmatism
(delta-RA). Results. Preoperatively, astigmatism values were greatest with simKa
from R1 to R5 and greatest with TCRPa from R6 to R8. Astigmatism values were
smallest with TNPa from R1 to R7. Postoperatively, astigmatism values were
greatest with simKa from R1 to R5 and greatest with TCRPa from R6 to R8. Delta
TCRP3 and Delta-TCRP4 matched delta-SE most closely, and delta-TCRPa3 matched
delta-RA most closely. Conclusions. TCRP proved to be the most accurate method in
estimating corneal power and astigmatism both before and after SMILE surgery.
PMID- 28421141
TI - Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the
Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect.
AB - Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related
peptides. In the brain, it activates the renin angiotensin system and causes
hypertension. Limited data are available on the dipsogenic effect of APA and
pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats
received intracerebroventricular (icv) APA in a conscious, unrestrained state
after pretreatment with (i) vehicle, (ii) 80 MUg of telmisartan, an Ang II type-1
(AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor,
and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration
of 400 and 800 ng of APA increased blood pressure by 12.6 +/- 3.0 and 19.0 +/-
3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to
APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 +/- 2.2 mmHg
versus telmisartan: 10.4 +/- 3.2 mmHg). Pressor response to APA was also
attenuated with amastatin and HOE-140 (vehicle: 26.5 +/- 1.1 mmHg, amastatin:
14.4 +/- 4.2 mmHg, HOE-140: 16.4 +/- 2.2 mmHg). In conclusion, APA increase in
the brain evokes a pressor response via enzymatic activity without dipsogenic
effect. AT1 receptors and B2 receptors in the brain may contribute to the APA
induced pressor response.
PMID- 28421142
TI - Plackett-Burman Design for rGILCC1 Laccase Activity Enhancement in Pichia
pastoris: Concentrated Enzyme Kinetic Characterization.
AB - Laccases are multicopper oxidases that catalyze aromatic and nonaromatic
compounds with concomitant reduction of molecular oxygen to water. They are of
great interest due to their potential biotechnological applications. In this work
we statistically improved culture media for recombinant GILCC1 (rGILCC1) laccase
production at low scale from Ganoderma lucidum containing the construct
pGAPZalphaA-GlucPost-Stop in Pichia pastoris. Temperature, pH stability, and
kinetic parameter characterizations were determined by monitoring concentrate
enzyme oxidation at different ABTS substrate concentrations. Plackett-Burman
Design allowed improving enzyme activity from previous work 36.08-fold, with a
laccase activity of 4.69 +/- 0.39 UL-1 at 168 h of culture in a 500 mL shake
flask. Concentrated rGILCC1 remained stable between 10 and 50 degrees C and
retained a residual enzymatic activity greater than 70% at 60 degrees C and 50%
at 70 degrees C. In regard to pH stability, concentrated enzyme was more stable
at pH 4.0 +/- 0.2 with a residual activity greater than 90%. The lowest residual
activity greater than 55% was obtained at pH 10.0 +/- 0.2. Furthermore,
calculated apparent enzyme kinetic parameters were a Vmax of 6.87 * 10-5 mM s-1,
with an apparent Km of 5.36 * 10-2 mM. Collectively, these important stability
findings open possibilities for applications involving a wide pH and temperature
ranges.
PMID- 28421143
TI - The Dual Burden of Malnutrition and Associated Dietary and Lifestyle Habits among
Lebanese School Age Children Living in Orphanages in North Lebanon.
AB - Childhood is a crucial period affecting physical and intellectual development.
Although children living in orphanages are among the most vulnerable groups at
risk of malnutrition, there is scarcity of data concerning their nutritional
status in Lebanon. To investigate these data, a cross-sectional survey was
conducted including a sample of 153 institutionalized children aged 5-14 years
from all orphanages in Tripoli. Nutritional status was assessed using
anthropometric, clinical, and dietary tools. Interpretation of anthropometric
data showed that 13.8% were stunted while the prevalence of overweight/obesity
was 9.2% according to the World Health Organization (WHO) reference criteria.
Physical signs suggesting nutritional deficiencies were detected in about 25% of
the sample. Dietary intake evaluation showed that about half of the participants
had inadequate dietary intakes of proteins, fruits, and vegetables and 92% had
inadequate milk and dairy intakes recommended for their age specific needs.
Multivariate regression analysis revealed statistically significant positive
association of age, skipping breakfast, and increased screen time with stunting
while it showed statistically significant negative association of inadequate
protein intake with overweight/obesity. The coexistence of under- and
overnutrition among institutionalized children calls for implementation of
comprehensive intervention strategies committed to reducing undernutrition while
simultaneously preventing overnutrition through improving diet quality and
physical activity of these children.
PMID- 28421144
TI - Prevalence of Sarcopenic Obesity in Adults with Class II/III Obesity Using
Different Diagnostic Criteria.
AB - Background/Objective. Sarcopenic obesity (SO) is a hidden condition of reduced
lean soft tissue (LST) in context of excess adiposity. SO is most commonly
reported in older adults and both its risk and prevalence increase with age. A
variety of body composition indices and cut points have been used to define this
condition, leading to conflicting prevalence and risk prediction. Here, we
investigate variability in the prevalence of SO in an adult sample of individuals
with class II/III obesity (BMI >= 35 kg/m2) using different diagnostic criteria.
Methods. SO definitions were identified from a literature review of studies using
dual-energy X-ray absorptiometry (DXA) to assess LST. Demographics,
anthropometrics, and body composition (by DXA) were measured in n = 120, 86%
female (46.9 +/- 11.1 years). Results. LST was extremely variable in individuals,
even with similar body sizes, and observed across the age spectrum. The
prevalence of SO ranged from 0 to 84.5% in females and 0 to 100% in males,
depending upon the definition applied, with higher prevalence among definitions
accounting for measures of body size or fat mass. Conclusion. SO is present, yet
variable, in adults with class II/III obesity. Accounting for body mass or fat
mass may identify a higher number of individuals with SO, although risk
prediction remains to be studied.
PMID- 28421145
TI - A Framework for Describing the Influence of Service Organisation and Delivery on
Participation in Fetal Anomaly Screening in England.
AB - Objective. The aim of this research was to explore the influence of service
organisation and delivery on providers and users' interactions and decision
making in the context of Down's syndrome screening. Methods. A qualitative
descriptive study involving online interviews conducted with a purposive sample
of 34 community midwives, 35 pregnant women, and 15 partners from two maternity
services in different health districts in England. Data were analysed using a
combination of grounded theory principles and content analysis and a framework
was developed. Results. The main emerging concepts were organisational
constraints, power, routinisation, and tensions. Providers were concerned about
being time-limited that encouraged routine, minimal information-giving and lacked
skills to check users' understanding. Users reported their participation was
influenced by providers' attitudes, the ambience of the environment, asymmetric
power relations, and the offer and perception of screening as a routine test.
Discordance between the national programme's policy of nondirective informed
choice and providers' actions of recommending and arranging screening
appointments was unexpected. Additionally, providers and users differing
perceptions of emotional effects of information, beliefs, and expectations
created tensions within them, between them, and in the antenatal environment.
Conclusions. A move towards a social model of care may be beneficial to empower
service users and create less tension for providers and users.
PMID- 28421146
TI - Breastfeeding after Gestational Diabetes: Does Perceived Benefits Mediate the
Relationship?
AB - Introduction. Breastfeeding is recognized as one of the best ways to decrease
infant mortality and morbidity. However, women with gestational diabetes mellitus
(GDM) may have breastfeeding barriers due to the increased risk of neonatal and
pregnancy complications. While the prevalence of GDM is increasing worldwide, it
is important to understand the full implications of GDM on breastfeeding
outcomes. The current study aims to investigate the (1) direct effect of GDM on
breastfeeding duration and (2) indirect effect of GDM on breastfeeding duration
through perceived benefits of breastfeeding. Methods. Prospective cohort data
from the Infant Feeding and Practices Study II was analyzed (N = 4,902).
Structural equation modeling estimated direct and indirect effects. Results.
Perceived benefits of breastfeeding directly influenced breastfeeding duration
(beta = 0.392, p <= 0.001). GDM was not directly associated with breastfeeding
duration or perceived benefits of breastfeeding. Similarly, GDM did not have an
indirect effect on breastfeeding duration through perceived benefits of
breastfeeding. Conclusions. Perceived benefits of breastfeeding are an important
factor associated with breastfeeding duration. Maternal and child health care
professionals should enhance breastfeeding education efforts.
PMID- 28421147
TI - Electrophysiological, Morphological, and Ultrastructural Features of the Injured
Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood
Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.
AB - In this study, we examined the efficacy of human umbilical cord blood mononuclear
cells (hUCB-MCs), genetically modified with the VEGF and GDNF genes using
adenoviral vectors, on posttraumatic regeneration after transplantation into the
site of spinal cord injury (SCI) in rats. Thirty days after SCI, followed by
transplantation of nontransduced hUCB-MCs, we observed an improvement in H
(latency period, LP) and M(Amax) waves, compared to the group without therapy
after SCI. For genetically modified hUCB-MCs, there was improvement in Amax of M
wave and LP of both the M and H waves. The ratio between Amax of the H and M
waves (Hmax/Mmax) demonstrated that transplantation into the area of SCI of
genetically modified hUCB-MCs was more effective than nontransduced hUCB-MCs.
Spared tissue and myelinated fibers were increased at day 30 after SCI and
transplantation of hUCB-MCs in the lateral and ventral funiculi 2.5 mm from the
lesion epicenter. Transplantation of hUCB-MCs genetically modified with the VEGF
and GNDF genes significantly increased the number of spared myelinated fibers (22
fold, P > 0.01) in the main corticospinal tract compared to the nontransduced
ones. HNA+ cells with the morphology of phagocytes and microglia-like cells were
found as compact clusters or cell bridges within the traumatic cavities that were
lined by GFAP+ host astrocytes. Our results show that hUCB-MCs transplanted into
the site of SCI improved regeneration and that hUCB-MCs genetically modified with
the VEGF and GNDF genes were more effective than nontransduced hUCB-MCs.
PMID- 28421148
TI - Multidisciplinary Approach in the Management of a Complex Case: Implant
Prosthetic Rehabilitation of a Periodontal Smoking Patient with Partial
Edentulism, Malocclusion, and Aesthetic Diseases.
AB - Complex periprosthetic cases are considered as challenges by clinicians. Clinical
and radiographic parameters should be considered separately to make the right
choice between an endodontically or periodontally compromised treated tooth and
implant. Therefore, in order to decide whether the tooth is safe or not, data
that have to be collected are specific parameters of both the patient and the
clinician. In addition, the presence of periodontal, prosthetic, and orthodontic
diseases requires patients to be set in multidisciplinary approach. The aim of
this case report is to describe how the multidisciplinary approach could be the
best way to manage difficult cases of implant-prosthetic rehabilitation. How to
rehabilitate with fixed prosthesis on natural teeth and dental implants a smoker
patient who presents with active periodontitis, multiple edentulous areas, dental
malocclusion, and severe aesthetic problems was also described.
PMID- 28421149
TI - Eccrine Nevus Presenting with Umbilical Discharge: A Case Report and Review of
the Literature.
AB - Eccrine nevus is a rare skin lesion with protean manifestations like
hyperhidrosis, discolored nodules, papules, and so forth, which has been reported
in various anatomic parts of the body including the forearm, leg, thigh, back,
and coccyx. Our patient was a 26-year-old male, who presented with increasing
colorless and odorless episodic umbilical discharge. First impression for the
patient was an umbilical sinus and the patient underwent surgery.
Histopathological study revealed the lesion to be an eccrine nevus of the
umbilicus. This is the first case of eccrine nevus presenting with umbilical
discharge. We recommend that eccrine nevus should be considered as a differential
diagnosis for umbilical discharge.
PMID- 28421150
TI - Post-ERCP Emphysematous Cholecystitis in a Young Woman: A Rare and Potentially
Fatal Complication.
AB - A 45-year-old woman with suspected Functional Biliary Sphincter Disorder (FBSD)
developed Clostridium perfringens related emphysematous cholecystitis after ERCP.
A low index of suspicion for emphysematous cholecystitis in this young, otherwise
healthy woman led to a significant delay in making the correct diagnosis, and air
in the gallbladder was wrongly attributed to a possible gallbladder perforation.
ERCP is associated with significant risks, particularly in patients with FBSD,
where diagnostic uncertainty renders the balance of risk versus benefit even more
critical. Post-ERCP emphysematous cholecystitis secondary to Clostridium
perfringens is a rare but potentially fatal complication.
PMID- 28421151
TI - Extramedullary Relapse in a CML Patient after Allogeneic Stem Cell
Transplantation.
AB - Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature
granulocytic cells. It is a rare entity during the course of CML patients
especially after allogeneic stem cell transplantation (SCT). Relapse without bone
marrow involvement is much rarer. We report a case of CML patient who relapsed
with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and
molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was
performed because of refractory disease to tyrosine kinase inhibitors. Complete
cytogenetic and molecular response was achieved after allogeneic SCT followed by
dasatinib treatment. Approximately 5 years after the transplantation, very
rapidly progressive lesion was documented and diagnosed as GS although he was at
molecular and cytogenetic remission. The patient died during chemotherapy due to
sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML
patients with molecular and cytogenetic remission. Since it is a very aggressive
disease with a poor prognosis, combined chemoradiotherapies with other possible
options like DLI or second allogeneic SCT should be considered as soon as the
diagnosis is confirmed.
PMID- 28421152
TI - Spontaneous Adrenal Hemorrhage in Pregnancy: A Case Series.
AB - Background. Abdominal pain during pregnancy has a broad differential diagnosis
which includes spontaneous adrenal hemorrhage (SAH). There is scant literature
available on optimal mode of delivery in stable patients. Cases. Patient 1 was a
35-year-old nullipara who presented at 36 weeks of gestation with left flank
pain. Patient 2 was a 27-year-old multipara at 38 weeks who presented with left
upper quadrant pain. Diagnosis of SAH was made by CT scan and both were managed
with pain control, serial hemoglobin assessments, and abdominal exams resulting
in uncomplicated vaginal deliveries. Conclusion. SAH, although rare, is an
important consideration when evaluating abdominal and flank pain in pregnancy.
Management options vary from conservative management to surgical intervention
depending on the stability of the patient.
PMID- 28421153
TI - Breast Cancer Suspicion in a Transgender Male-to-Female Patient on Hormone
Replacement Therapy Presenting with Right Breast Mass: Breast Cancer Risk
Assessment and Presentation of a Rare Lesion.
AB - There has been an increasing use of hormonal therapy among male-to-female (MtF)
transgender individuals. This long-term hormone replacement therapy (HRT) renders
MtF individuals a unique patient subgroup in terms of breast cancer risk. This
case describes a MtF transgender who presented with a breast lesion concerning
for malignancy following hormonal replacement therapy. The patient additionally
had a strong family history of breast cancer. Final pathology revealed lobular
hyperplasia in the setting of gynecomastia and pseudoangiomatous stromal
hyperplasia (PASH). Both pathology findings are rare in biological females, let
alone in the setting of hormone replacement therapy in a MtF individual. While
the number of reported cases of suspicious breast lesions in this population
remains scarce, it presents both a diagnostic and therapeutic challenge due to
the nature of the treatment course and the lack of research in this recently
growing subgroup of patients.
PMID- 28421154
TI - Aggressive Digital Papillary Adenocarcinoma of the Hand Presenting as a Felon.
AB - Aggressive digital papillary adenocarcinoma is a rare eccrine sweat gland
malignancy that is frequently misdiagnosed at initial presentation.
Histologically, this tumor is similar in appearance to many adenocarcinomas and
as such may be diagnosed as a metastatic lesion. We present the case of a patient
with digital papillary adenocarcinoma, which was initially diagnosed as a felon.
No consensus has been published regarding the treatment of this disease. A review
of the diagnosis, pathology, treatment, and adjunctive treatments of aggressive
digital papillary adenocarcinoma are also included.
PMID- 28421155
TI - An Appendiceal Carcinoid Tumor within an Amyand's Hernia Mimicking an
Incarcerated Inguinal Hernia.
AB - Introduction. We report the case of an appendiceal carcinoid tumor within an
Amyand's hernia, presenting as an incarcerated right inguinal hernia.
Presentation of Case. A 52-year-old male presented in the emergency department
due to a persistent right inguinal pain. Clinical examination revealed a tender
right groin mass. Laboratory tests revealed leukocytosis and an increased serum
CRP. Under the diagnosis of an incarcerated right inguinal hernia, an emergency
operation was taken. Intraoperatively, an inflamed appendix and a part of the
cecum were found in the hernia sac. The operation was completed with an
appendectomy and a modified Bassini hernia repair. Histological examination
revealed a carcinoid tumor, resulting in the performance of a right
hemicolectomy. Discussion. Amyand's hernia is estimated to account for 0.4% to
0.6% of all inguinal hernias. Coexistence of an Amyand's hernia and a neoplasia
is quite rare. Carcinoids are the most frequent tumors found in the appendix,
with the size of the primary tumor to be considered the most important prognostic
factor and the basis upon which the operative plan is decided. Conclusion. A
malignancy of the appendix should always be in the differential diagnosis of a
right inguinal mass, in order to provide optimum surgical treatment.
PMID- 28421157
TI - Psoriatic Arthritis Is an Indicator of Significant Renal Damage in Patients with
Psoriasis: An Observational and Epidemiological Study.
AB - Background. Psoriasis affects joints in around 30% of the patients. Recent
studies have demonstrated an increased risk of essential hypertension, ischemic
heart disease, and stroke in psoriatic patients. However, the prevalence of renal
disease in patients with psoriasis has not been evaluated properly. Objectives.
Objectives were to evaluate renal functions in patients with psoriasis and to
assess any possible relationship of renal failure with psoriasis and psoriatic
arthritis. Methods. In this cross-sectional study, 30 participants were recruited
into the following three groups: group-A, psoriatic arthritis; group-B, psoriasis
without arthritis; and group-C, healthy subjects. Renal function tests were
performed for every participant of each group. The data was analyzed by using
SPSS version 16. Chi-squared and one-way ANOVA tests were applied, considering a
P value of less than 0.05 as a standard criterion. Results. Serum creatinine,
urea, and phosphate were the highest in group-A, higher in group-B, and normal in
group-C, P < 0.05. Similarly, GFR was the lowest in group-A, lower in group-B,
and normal in group-C. The difference in mean GFR values was statistically
significant, F(2) = 355, P < 0.001. Moreover, proteinuria (gm/day) was seen in
96.7% of the patients with psoriatic arthritis, (M = 1.18 +/- 0.55, P < 0.05)
against 10% of the psoriatic patients without arthritis (M = 0.41 +/- 0.10, P <
0.05). Conclusion. Derangement of renal function is more prevalent in psoriatic
patients, especially in those with concomitant psoriatic arthritis. Therefore,
each psoriatic patient must be routinely screened for an underlying renal
failure.
PMID- 28421156
TI - The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative
Pharmacogenetics and Pharmacometabolomics.
AB - Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients
undergoing percutaneous coronary intervention. However, the variable platelets
reactivity response to clopidogrel may lead to outcome failure and recurrence of
cardiovascular events. Although many genetic and nongenetic factors are known,
great portion of clopidogrel variable platelets reactivity remain unexplained
which challenges the personalization of clopidogrel therapy. Current methods for
clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and
platelets function testing. However, these methods lack precise prediction of
clopidogrel outcome, often leading to insufficient prediction.
Pharmacometabolomics which is an approach to identify novel biomarkers of drug
response or toxicity in biofluids has been investigated to predict drug response.
The advantage of pharmacometabolomics is that it does not only predict the
response but also provide extensive information on the metabolic pathways
implicated with the response. Integrating pharmacogenetics with
pharmacometabolomics can give insight on unknown genetic and nongenetic factors
associated with the response. This review aimed to review the literature on
factors associated with the variable platelets reactivity response to
clopidogrel, as well as appraising current methods for the personalization of
clopidogrel therapy. We also aimed to review the literature on using
pharmacometabolomics approach to predict drug response, as well as discussing the
plausibility of using it to predict clopidogrel outcome.
PMID- 28421158
TI - Cytotoxicity of Zardaverine in Embryonal Rhabdomyosarcoma from a Costello
Syndrome Patient.
AB - Costello syndrome (CS) patients suffer from a very high 10% incidence of
embryonal rhabdomyosarcoma (ERMS). As tools to discover targeted therapeutic
leads, we used a CS patient-derived ERMS cell line (CS242 ERMS) harboring a
homozygous p.G12A mutation in HRAS, and a control cell line derived from the same
patient comprising non-malignant CS242 fibroblasts with a heterozygous p.G12A
HRAS mutation. A library of 2,000 compounds with known pharmacological activities
was screened for their effect on CS242 ERMS cell viability. Follow-up testing in
a panel of cell lines revealed that various compounds originally developed for
other indications were remarkably selective; notably, the phosphodiesterase (PDE)
inhibitor zardaverine was at least 1,000-fold more potent in CS242 ERMS than in
the patient-matched non-malignant CS242 fibroblasts, other ERMS, or normal
fibroblasts. Chronic treatment with zardaverine led to the emergence of resistant
cells, consistent with CS242 ERMS comprising a mixed population of cells. Many
PDE inhibitors in addition to zardaverine were tested on CS242 ERMS, but almost
all had no effect. Interestingly, zardaverine and analogs showed a similar
cytotoxicity profile in CS242 ERMS and cervical carcinoma-derived HeLa cells,
suggesting a mechanism of action common to both cell types that does not require
the presence of an HRAS mutation (HeLa contains wild type HRAS). Two recent
studies presented possible mechanistic explanations for the cytotoxicity of
zardaverine in HeLa cells. One revealed that zardaverine inhibited a HeLa cell
based screen measuring glucocorticoid receptor (GR) activation; however, using
engineered HeLa cells, we ruled out a specific effect of zardaverine on signaling
through the GR. The second attributed zardaverine toxicity in HeLa cells to
promotion of the interaction of phosphodiesterase 3A and the growth regulatory
protein Schlafen 12. We speculate that this work may provide a possible mechanism
for zardaverine action in CS242 ERMS, although we have not yet tested this
hypothesis. In conclusion, we have identified zardaverine as a potent cytotoxic
agent in a CS-derived ERMS cell line and in HeLa. Although we have ruled out some
possibilities, the mechanism of action of zardaverine in CS242 ERMS remains to be
determined.
PMID- 28421159
TI - Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic
Reprogramming.
AB - Tumor cells reprogram their metabolism to survive and grow in a challenging
microenvironment. Some of this reprogramming is performed by epigenetic
mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying
enzymes are dependent on substrates that are also key metabolic intermediates. We
have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an
epigenetic regulator, is necessary for rapid breast cancer cell proliferation.
The mechanism for this requirement is the BRG1-dependent transcription of key
lipogenic enzymes and regulators. Reduction in lipid synthesis lowers
proliferation rates, which can be restored by palmitate supplementation. This
work has established BRG1 as an attractive target for breast cancer therapy.
Unlike genetic alterations, epigenetic mechanisms are reversible, promising
gentler therapies without permanent off-target effects at distant sites.
PMID- 28421160
TI - The Unfolded Protein Response: At the Intersection between Endoplasmic Reticulum
Function and Mitochondrial Bioenergetics.
AB - Endoplasmic reticulum (ER) to mitochondria communication has emerged in recent
years as a signaling hub regulating cellular physiology with a relevant
contribution to diseases including cancer and neurodegeneration. This functional
integration is exerted through discrete interorganelle structures known as
mitochondria-associated membranes (MAMs). At these domains, ER/mitochondria
physically associate to dynamically adjust metabolic demands and the response to
stress stimuli. Here, we provide a focused overview of how the ER shapes the
function of the mitochondria, giving a special emphasis to the significance of
local signaling of the unfolded protein response at MAMs. The implications to
cell fate control and the progression of cancer are also discussed.
PMID- 28421161
TI - Incidence of Immune-Related Adverse Events with Program Death Receptor-1- and
Program Death Receptor-1 Ligand-Directed Therapies in Genitourinary Cancers.
AB - Program death receptor-1 (PD-1) and program death receptor-1 ligand (PD-L1)
inhibitors are increasingly being used in the clinic to treat a growing number of
malignancies, including many genitourinary (GU) malignancies. These immune-based
therapies have demonstrated a distinct toxicity profile compared to traditional
chemotherapy and the targeted therapies directed at the vascular endothelial
growth factor pathway or the mammalian target of rapamycin pathway. Autoimmune
toxicity targeting the skin, gastrointestinal tract, or the endocrine organs are
some of the more common adverse events (AEs) noted with these therapies. Here in,
we report the results of a systematic review of the incidence of toxicities in GU
cancers reported in the phase II or phase III clinical trials using single-agent
PD-1 or PD-L1 inhibitors. Overall, the rate of serious (grades 3-4) AEs was noted
in approximately 15% of patients. The AEs noted were similar between all the
agents tested, highlighting the overall class effect of these therapies. The
incidence in GU cancers is similar to those seen in other malignancies. Given the
widespread and high volume real-world use of these agents, it is important for
oncologists to be familiar with these side effects to minimize the risks for
patients while undergoing therapy.
PMID- 28421162
TI - R-IDEAL: A Framework for Systematic Clinical Evaluation of Technical Innovations
in Radiation Oncology.
AB - The pace of innovation in radiation oncology is high and the window of
opportunity for evaluation narrow. Financial incentives, industry pressure, and
patients' demand for high-tech treatments have led to widespread implementation
of innovations before, or even without, robust evidence of improved outcomes has
been generated. The standard phase I-IV framework for drug evaluation is not the
most efficient and desirable framework for assessment of technological
innovations. In order to provide a standard assessment methodology for clinical
evaluation of innovations in radiotherapy, we adapted the surgical IDEAL
framework to fit the radiation oncology setting. Like surgery, clinical
evaluation of innovations in radiation oncology is complicated by continuous
technical development, team and operator dependence, and differences in quality
control. Contrary to surgery, radiotherapy innovations may be used in various
ways, e.g., at different tumor sites and with different aims, such as radiation
volume reduction and dose escalation. Also, the effect of radiation treatment can
be modeled, allowing better prediction of potential benefits and improved patient
selection. Key distinctive features of R-IDEAL include the important role of
predicate and modeling studies (Stage 0), randomization at an early stage in the
development of the technology, and long-term follow-up for late toxicity. We
implemented R-IDEAL for clinical evaluation of a recent innovation in radiation
oncology, the MRI-guided linear accelerator (MR-Linac). MR-Linac combines a
radiotherapy linear accelerator with a 1.5-T MRI, aiming for improved targeting,
dose escalation, and margin reduction, and is expected to increase the use of
hypofractionation, improve tumor control, leading to higher cure rates and less
toxicity. An international consortium, with participants from seven large cancer
institutes from Europe and North America, has adopted the R-IDEAL framework to
work toward coordinated, evidence-based introduction of the MR-Linac. R-IDEAL
holds the promise for timely, evidence-based introduction of radiotherapy
innovations with proven superior effectiveness, while preventing unnecessary
exposure of patients to potentially harmful interventions.
PMID- 28421163
TI - Phase I Trial of Triapine-Cisplatin-Paclitaxel Chemotherapy for Advanced Stage or
Metastatic Solid Tumor Cancers.
AB - Ribonucleotide reductase (RNR) is an enzyme involved in the de novo synthesis of
deoxyribonucleotides, which are critical for DNA replication and DNA repair.
Triapine is a small-molecule RNR inhibitor. A phase I trial studied the safety of
triapine in combination with cisplatin-paclitaxel in patients with advanced stage
or metastatic solid tumor cancers in an effort to capitalize on disrupted DNA
damage repair. A total of 13 patients with various previously treated cancers
were given a 96-h continuous intravenous (i.v.) infusion of triapine (40-120
mg/m2) on day 1, and then 3-h i.v. paclitaxel (80 mg/m2) followed by 1-h i.v.
cisplatin (50-75 mg/m2) on day 3. This combination regimen was repeated every 21
days. The maximum tolerated dose (MTD) for each agent was identified to be
triapine (80 mg/m2), cisplatin (50 mg/m2), and paclitaxel (80 mg/m2). Common
grade 3 or 4 toxicities included reversible anemia, leukopenia, thrombocytopenia,
or electrolyte abnormalities. The combination regimen of triapine-cisplatin
paclitaxel resulted in no objective responses; however, five (83%) of six
patients treated at the MTD had stable disease between 1 and 8 months duration.
This phase I study showed that the combination regimen of triapine-cisplatin
paclitaxel was safe and provides a rational basis for a follow-up phase II trial
to evaluate efficacy and progression-free survival in women with metastatic or
recurrent uterine cervix cancer.
PMID- 28421164
TI - "Targeted" Chemotherapy for Esophageal Cancer.
PMID- 28421165
TI - The Diverse Cellular and Animal Models to Decipher the Physiopathological Traits
of Mycobacterium abscessus Infection.
AB - Mycobacterium abscessus represents an important respiratory pathogen among the
rapidly-growing non-tuberculous mycobacteria. Infections caused by M. abscessus
are increasingly found in cystic fibrosis (CF) patients and are often refractory
to antibiotic therapy. The underlying immunopathological mechanisms of
pathogenesis remain largely unknown. A major reason for the poor advances in M.
abscessus research has been a lack of adequate models to study the acute and
chronic stages of the disease leading to delayed progress of evaluation of
therapeutic efficacy of potentially active antibiotics. However, the recent
development of cellular models led to new insights in the interplay between M.
abscessus with host macrophages as well as with amoebae, proposed to represent
the environmental host and reservoir for non-tuberculous mycobacteria. The
zebrafish embryo has also appeared as a useful alternative to more traditional
models as it recapitulates the vertebrate immune system and, due to its optical
transparency, allows a spatio-temporal visualization of the infection process in
a living animal. More sophisticated immunocompromised mice have also been
exploited recently to dissect the immune and inflammatory responses to M.
abscessus. Herein, we will discuss the limitations, advantages and potential
offered by these various models to study the pathophysiology of M. abscessus
infection and to assess the preclinical efficacy of compounds active against this
emerging human pathogen.
PMID- 28421166
TI - In vivo and In vitro Interactions between Pseudomonas aeruginosa and
Staphylococcus spp.
AB - The significance of polymicrobial infections is increasingly being recognized
especially in a biofilm context wherein multiple bacterial species-including both
potential pathogens and members of the commensal flora-communicate, cooperate,
and compete with each other. Two important bacterial pathogens that have
developed a complex network of evasion, counter-inhibition, and subjugation in
their battle for space and nutrients are Pseudomonas aeruginosa and
Staphylococcus aureus. Their strain- and environment-specific interactions, for
instance in the cystic fibrosis lung or in wound infections, show severe
competition that is generally linked to worse patient outcomes. For instance, the
extracellular factors secreted by P. aeruginosa have been shown to subjugate S.
aureus to persist as small colony variants (SCVs). On the other hand, data also
exist where S. aureus inhibits biofilm formation by P. aeruginosa but also
protects the pathogen by inhibiting its phagocytosis. Interestingly, such
interspecies interactions differ between the planktonic and biofilm phenotype,
with the extracellular matrix components of the latter likely being a key, and
largely underexplored, influence. This review attempts to understand the complex
relationship between P. aeruginosa and Staphylococcus spp., focusing on S.
aureus, that not only is interesting from the bacterial evolution point of view,
but also has important consequences for our understanding of the disease
pathogenesis for better patient management.
PMID- 28421167
TI - Iron and Virulence in Francisella tularensis.
AB - Francisella tularensis, the causative agent of tularemia, is a Gram-negative
bacterium that infects a variety of cell types including macrophages, and
propagates with great efficiency in the cytoplasm. Iron, essential for key
enzymatic and redox reactions, is among the nutrients required to support this
pathogenic lifestyle and the bacterium relies on specialized mechanisms to
acquire iron within the host environment. Two distinct pathways for iron
acquisition are encoded by the F. tularensis genome- a siderophore-dependent
ferric iron uptake system and a ferrous iron transport system. Genes of the Fur
regulated fslABCDEF operon direct the production and transport of the siderophore
rhizoferrin. Siderophore biosynthesis involves enzymes FslA and FslC, while
export across the inner membrane is mediated by FslB. Uptake of the rhizoferrin-
ferric iron complex is effected by the siderophore receptor FslE in the outer
membrane in a TonB-independent process, and FslD is responsible for uptake across
the inner membrane. Ferrous iron uptake relies largely on high affinity transport
by FupA in the outer membrane, while the Fur-regulated FeoB protein mediates
transport across the inner membrane. FslE and FupA are paralogous proteins,
sharing sequence similarity and possibly sharing structural features as well.
This review summarizes current knowledge of iron acquisition in this organism and
the critical role of these uptake systems in bacterial pathogenicity.
PMID- 28421168
TI - Contribution of the A. baumannii A1S_0114 Gene to the Interaction with Eukaryotic
Cells and Virulence.
AB - Genetic and functional studies showed that some components of the Acinetobacter
baumannii ATCC 17978 A1S_0112-A1S_0119 gene cluster are critical for biofilm
biogenesis and surface motility. Recently, our group has shown that the A1S_0114
gene was involved in biofilm formation, a process related with pathogenesis.
Confirming our previous results, microscopy images revealed that the ATCC 17978
Delta0114 derivative lacking this gene was unable to form a mature biofilm
structure. Therefore, other bacterial phenotypes were analyzed to determine the
role of this gene in the pathogenicity of A. baumannii ATCC 17978. The
interaction of the ATCC 17978 parental strain and the Delta0114 mutant with A549
human alveolar epithelial cells was quantified revealing that the A1S_0114 gene
was necessary for proper attachment to A549 cells. This dependency correlates
with the negative effect of the A1S_0114 deletion on the expression of genes
coding for surface proteins and pili-assembly systems, which are known to play a
role in adhesion. Three different experimental animal models, including
vertebrate and invertebrate hosts, confirmed the role of the A1S_0114 gene in
virulence. All of the experimental infection assays indicated that the virulence
of the ATCC 17978 was significantly reduced when this gene was inactivated.
Finally, we discovered that the A1S_0114 gene was involved in the production of a
small lipopeptide-like compound herein referred to as acinetin 505 (Ac-505). Ac
505 was isolated from ATCC 17978 spent media and its chemical structure was
interpreted by mass spectrometry. Overall, our observations provide novel
information on the role of the A1S_0114 gene in A. baumannii's pathobiology and
lay the foundation for future work to determine the mechanisms by which Ac-505,
or possibly an Ac-505 precursor, could execute critical functions as a secondary
metabolite.
PMID- 28421169
TI - High Prevalence of Virulence Genes in Specific Genotypes of Atypical
Enteropathogenic Escherichia coli.
AB - Atypical enteropathogenic Escherichia coli (aEPEC) strains are emerging
enteropathogens that have been detected worldwide. A collection of 228 aEPEC
strains (121 from diarrheal patients, 27 from healthy carriers, 47 from animals
and 33 from raw meats) were investigated for serotypes, virulence gene profiles
and phylogenetic relationships. Sixty-six O serogroups were identified. Serogroup
O51 was the most prevalent, followed by O119, O26 and O76. For the 20 virulence
genes detected, statistically significant differences were observed in the
overall prevalence of efa1 (lifA), nleB, nleE, set/ent, paa, and ehxA genes among
strains from diarrheal patients, healthy carriers, animals and raw meats,
respectively. Strains from diarrheal patients had significantly higher levels of
efa1 (lifA) (29.8 vs. 0%, P = 0.0002), nleB (41.3 vs. 7.4%, P = 0.0004), nleE
(43.8 vs. 7.4%, P = 0.0002) and set/ent (41.3 vs. 7.4%, P = 0.0004) genes than
strains obtained from healthy carriers. The paa gene was identified more often in
isolates from raw meats (63.6 vs. 14.8%, P < 0.0001), animals (42.6 vs. 14.8%, P
< 0.0122), and diarrheal patients (36.4 vs. 14.8%, P < 0.0225) than in strains
obtained from healthy carriers. The ehxA gene was detected more frequently in
strains from raw meats than in strains from diarrheal patients (27.3 vs. 2.5%, P
= 0.0000) and healthy carriers (27.3 vs. 7.4%, P = 0.0474). The phylogenetic
marker, yjaA, was more frequently observed in strains among healthy carriers than
in diarrheal patient strains. Among the 228 aEPEC strains, 79 sequence types
(STs) were identified. The prominent STs, which comprised strains carrying the
four OI-122 genes and lpfA, were ST40, ST328, and ST29. Overall, the results
indicate that aEPEC strains isolated in China are highly heterogeneous. aEPEC
strains that are potentially more pathogenic appear to be related to specific STs
or clonal complexes and serotypes. The high prevalence of diarrhea-associated
genes in animal or raw meat strains suggests a zoonotic transmission pathway for
potentially human pathogenic aEPEC.
PMID- 28421170
TI - Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Stress
Granule Formation Depending on Protein Kinase R-like Endoplasmic Reticulum Kinase
(PERK) in MARC-145 Cells.
AB - Stress granules (SGs) are sites of mRNA storage that are formed in response to
various conditions of stress, including viral infections. Porcine reproductive
and respiratory syndrome virus (PRRSV) is an Arterivirus that has been
devastating the swine industry worldwide since the late 1980s. In this study, we
found that infection of PRRSV strain WUH3 (genotype 2 PRRSV) induced stable
formation of robust SGs in MARC-145 cells, as demonstrated by the recruitment of
marker proteins of SGs, including TIA1, G3BP1, and eIF3eta. Treatment with
specific inhibitors or siRNAs against the stress kinases that are involved in SG
formation revealed that PRRSV induced SG formation through a PERK (protein kinase
R-like endoplasmic reticulum kinase)-dependent mechanism. Impairment of SG
assembly by concomitant knockdown of the SG marker proteins (TIA1, G3BP1, and
TIAR) did not affect PRRSV growth, while significantly enhanced PRRSV-induced NF
kappaB subunit p65 phosphorylation and inflammatory cytokine production. Taken
together, our results demonstrate that PRRSV induces SG formation via a PERK
dependent pathway and that SGs are involved in the signaling pathway of the PRRSV
induced inflammatory response in MARC-145 cells.
PMID- 28421171
TI - Tactile Stimulation to Stimulate Spontaneous Breathing during Stabilization of
Preterm Infants at Birth: A Retrospective Analysis.
AB - BACKGROUND AND AIMS: Tactile maneuvers to stimulate breathing in preterm infants
are recommended during the initial assessment at birth, but it is not known how
often and how this is applied. We evaluated the occurrence and patterns of
tactile stimulation during stabilization of preterm infants at birth. METHODS:
Recordings of physiological parameters and videos of infants <32 weeks
gestational age were retrospectively analyzed. Details of tactile stimulation
during the first 7 min after birth (timing, duration, type, and indication) were
noted. RESULTS: Stimulation was performed in 164/245 (67%) infants. The median
(IQR) GA was 28 6/7 (27 2/7-30 1/7) weeks, birth weight 1,153 (880-1,385) g,
Apgar score at 5 min was 8 (7-9), 140/245 (57%) infants were born after cesarean
section, and 134/245 (55%) were male. There were no significant differences
between the stimulated and the non-stimulated infants with regard to basic
characteristics. In the stimulated infants, the first episode of stimulation was
given at a median (IQR) of 114 (73-182) s after birth. Stimulation was repeated 3
(1-5) times, with a median (IQR) duration of 8 (4-16) s and a total duration of
32 (15-64) s. Modes of stimulation were: rubbing (68%) or flicking (2%) the soles
of the feet, rubbing the back (12%), a combination (9%), or other (8%). In 67% of
the stimulation episodes, a clear indication was noted (25% bradycardia, 57%
apnea, 48% hypoxemia, 43% combination) and an effect was observed in 18% of these
indicated stimulation episodes. A total effect of all stimulation episodes per
infant remains unclear, but infants who did not receive stimulation were more
often intubated in the delivery room (14/79 (18%) vs 12/164 (7%), p < 0.05).
CONCLUSION: There was a large variation in the use of tactile stimulation in
preterm infants during stabilization at birth. In most cases, there was an
indication for stimulation, but only in a small proportion an effect could be
observed.
PMID- 28421172
TI - Aspiration Risk and Respiratory Complications in Patients with Esophageal
Atresia.
AB - Chronic, long-term respiratory morbidity (CRM) is common in patients with a
history of repaired congenital esophageal atresia, typically associated with
tracheoesophageal fistula (EA/TEF). EA/TEF patients are at high risk of having
aspiration, and retrospective studies have associated CRM with both recurrent
aspiration and atopy. However, studies evaluating the association between CRM in
this population and either aspiration or atopy have reported conflicting results.
Furthermore, CRM in this population may be due to other related conditions as
well, such as tracheomalacia and/or recurrent infections. Aspiration is difficult
to confirm, short of lung biopsy. Moreover, even within the largest evidence base
assessing the association between CRM and aspiration, which has evaluated the
potential relationship between gastroesophageal reflux and asthma, findings are
contradictory. Studies attempting to relate CRM to prior aspiration events may
inadequately estimate the frequency and severity of previous aspiration episodes.
There is convincing evidence documenting that chronic, massive aspiration in
patients with repaired EA/TEF is associated with the development of
bronchiectasis. While chronic aspiration is likely associated with other CRM in
patients with repaired EA/TEF, this does not appear to have been confirmed by the
data currently available. Prospective studies that systematically evaluate
aspiration risk and allergic disease in patients with repaired EA/TEF and
document subsequent CRM will be needed to clarify the causes of CRM in this
population. Given the prevalence of CRM, patients with repaired EA/TEF should
ideally receive regular follow-up by multidisciplinary teams with expertise in
this condition, throughout both childhood and adulthood.
PMID- 28421173
TI - Cerebral Autoregulation, Brain Injury, and the Transitioning Premature Infant.
AB - Improvements in clinical management of the preterm infant have reduced the rates
of the two most common forms of brain injury, such as severe intraventricular
hemorrhage and white matter injury, both of which are contributory factors in the
development of cerebral palsy. Nonetheless, they remain a persistent challenge
and are associated with a significant increase in the risk of adverse
neurodevelopment outcomes. Repeated episodes of ischemia-reperfusion represent a
common pathway for both forms of injury, arising from discordance between
systemic blood flow and the innate regulation of cerebral blood flow in the
germinal matrix and periventricular white matter. Nevertheless, establishing firm
hemodynamic boundaries, as a part of neuroprotective strategy, has challenged
researchers. Existing measures either demonstrate inconsistent relationships with
injury, as in the case of mean arterial blood pressure, or are not feasible for
long-term monitoring, such as cardiac output estimated by echocardiography. These
challenges have led some researchers to focus on the mechanisms that control
blood flow to the brain, known as cerebrovascular autoregulation. Historically,
the function of the cerebrovascular autoregulatory system has been difficult to
quantify; however, the evolution of bedside monitoring devices, particularly near
infrared spectroscopy, has enabled new insights into these mechanisms and how
impairment of blood flow regulation may contribute to catastrophic injury. In
this review, we first seek to examine how technological advancement has changed
the assessment of cerebrovascular autoregulation in premature infants. Next, we
explore how clinical factors, including hypotension, vasoactive medications,
acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the
preterm infant. Additionally, we examine how developmentally linked or acquired
dysfunction in cerebral autoregulation contributes to preterm brain injury. In
conclusion, we address exciting new approaches to the measurement of
autoregulation and discuss the feasibility of translation to the bedside.
PMID- 28421174
TI - Utility of Cardiovascular Magnetic Resonance-Derived Wave Intensity Analysis As a
Marker of Ventricular Function in Children with Heart Failure and Normal Ejection
Fraction.
AB - OBJECTIVE: This study sought to explore the diagnostic insight of cardiovascular
magnetic resonance (CMR)-derived wave intensity analysis to better study systolic
dysfunction in young patients with chronic diastolic dysfunction and preserved
ejection fraction (EF), comparing it against other echocardiographic and CMR
parameters. BACKGROUND: Evaluating systolic and diastolic dysfunctions in
children is challenging, and a gold standard method is currently lacking.
METHODS: Patients with presumed diastolic dysfunction [n = 18; nine aortic
stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were
compared with age-matched control subjects (n = 18). All patients had no mitral
or aortic incompetence, significant AS, or reduced systolic EF. E/A ratio, E/E'
ratio, deceleration time, and isovolumetric contraction time were assessed on
echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT),
ejection time (ET), and wave intensity analyses were calculated from CMR. The
latter was performed on CMR phase-contrast flow sequences, defining a ratio of
the peaks of the early systolic forward compression wave (FCW) and the end
systolic forward expansion wave (FEW). RESULTS: Significant differences between
patients and controls were seen in the E/E' ratio (8.7 +/- 4.0 vs. 5.1 +/- 1.3, p
= 0.001) and FCW/FEW ratio (2.5 +/- 1.6 vs. 7.2 +/- 4.2 * 10-5 m/s, p < 0.001),
as well as-as expected-LAVi (80.7 +/- 22.5 vs. 51.0 +/- 10.9 mL/m2, p < 0.001).
In particular, patients exhibited a lower FCW (2.5 +/- 1.6 vs. 7.2 +/- 4.2 * 10-5
m/s, p < 0.001) in the face of preserved EF (67 +/- 11 vs. 69 +/- 5%, p = 0.392),
as well as longer isovolumetric contraction time (49 +/- 7 vs. 34 +/- 7 ms, p <
0.001) and ET/AT (0.35 +/- 0.04 vs. 0.27 +/- 0.04, p < 0.001). CONCLUSION: This
study shows that the wave intensity-derived ratio summarizing systolic and
diastolic function could provide insight into ventricular function in children,
on top of CMR and echocardiography, and it was here able to identify an element
of ventricular dysfunction with preserved EF in a small group of young patients.
PMID- 28421176
TI - Distributed Learning: Revitalizing Anesthesiology Training in Resource-Limited
Ethiopia.
AB - BACKGROUND: Ethiopia has a significant paucity of available health-care workers.
Despite the increasing number of medical schools, there are not enough physician
instructors. Furthermore, availability and standardization of postgraduate
training are lacking. Modalities of e-learning have been shown to be successful
when used to impart medical education in other resource-limited countries. The
Emory University and Addis Ababa University (AAU) Departments of Anesthesiology
have formed a collaboration with the intent of improving the AAU Anesthesiology
residency program, one of two postgraduate training programs for anesthesiology
in Ethiopia. METHODS: An initial educational needs assessment identified areas in
the existing training program that required improvement. In this pilot study, we
describe how the current classroom-based curriculum is augmented by the
introduction of interactive educational sessions and distributed learning in the
form of video lectures. Video lectures covered topics based on areas identified
by Ethiopian residents and faculty. Interactive sessions included hands-on
ultrasound workshops and epidural placement practicums, a journal club, problem
based learning sessions, and a mock code simulation. Assessment of the additions
of the newly introduced blended learning technique was conducted via pre- and
posttests on the topics presented. RESULTS: Pre- to posttest score averages
increased from 54.5% to 83.6%. CONCLUSION: An expansion of educational resources
and modes of didactics are needed to fill the gaps that exist in Ethiopian
anesthesiology training. Incorporating distributed learning into the existing
didactic structure may lead to more efficacious instruction resulting in a higher
retention rate of information.
PMID- 28421175
TI - Factors Influencing Usability of a Smartphone App to Reduce Excessive Alcohol
Consumption: Think Aloud and Interview Studies.
AB - BACKGROUND: Interventions delivered by smartphone apps have the potential to help
drinkers reduce their consumption of alcohol. To optimize engagement and reduce
the high rates of attrition associated with the use of digital interventions, it
is necessary to ensure that an app's design and functionality is appropriate for
its intended purposes and target population. AIMS: To understand the usability of
an app to help people reduce their alcohol consumption. METHOD: The app, Drink
Less, contains a core module focusing on goal setting, supplemented by five
additional modules: self-monitoring and feedback, identity change, cognitive bias
re-training, action planning, and social comparison. Two studies were conducted,
a "think aloud" study performed with people using the app for the first time and
a semistructured interview study performed after users had had access to the app
for at least 2 weeks. A thematic analysis of the "think aloud" and interview
transcripts was conducted by one coder and verified by a second. RESULTS: Twenty
four participants, half of whom were women and half from disadvantaged groups,
took part in the two studies. Three main themes identified in the data were
"Feeling lost and unsure of what to do next," "Make the app easy to use," and
"Make the app beneficial and rewarding to use." These themes reflected
participants' need for (i) guidance, particularly when first using the app or
when entering data; (ii) the data entry process to be simple and the navigation
intuitive; (iii) neither the amount of text nor range of options to be
overwhelming; (iv) the app to reward them for effort and progress; and (v) it to
be clear how the app could help alcohol reduction goals be reached. CONCLUSION:
First-time and experienced users want an alcohol reduction app to be easy,
rewarding, and beneficial to use. An easy-to-use app would reduce user burden,
offer ongoing help, and be esthetically pleasing. A rewarding and beneficial app
would provide positive reinforcement, give feedback about progress, and
demonstrate credibility. Users need help when first using the app, and they need
a compelling reason to continue using it.
PMID- 28421177
TI - Variation in Population Vulnerability to Heat Wave in Western Australia.
AB - Heat waves (HWs) have killed more people in Australia than all other natural
hazards combined. Climate change is expected to increase the frequency, duration,
and intensity of HWs and leads to a doubling of heat-related deaths over the next
40 years. Despite being a significant public health issue, HWs do not attract the
same level of attention from researchers, policy makers, and emergency management
agencies compared to other natural hazards. The purpose of the study was to
identify risk factors that might lead to population vulnerability to HW in
Western Australia (WA). HW vulnerability and resilience among the population of
the state of WA were investigated by using time series analysis. The health
impacts of HWs were assessed by comparing the associations between hospital
emergency department (ED) presentations, hospital admissions and mortality data,
and intensities of HW. Risk factors including age, gender, socioeconomic status
(SES), remoteness, and geographical locations were examined to determine whether
certain population groups were more at risk of adverse health impacts due to
extreme heat. We found that hospital admissions due to heat-related conditions
and kidney diseases, and overall ED attendances, were sensitive indicators of HW.
Children aged 14 years or less and those aged 60 years or over were identified as
the most vulnerable populations to HWs as shown in ED attendance data. Females
had more ED attendances and hospital admissions due to kidney diseases; while
males had more heat-related hospital admissions than females. There were
significant dose-response relationships between HW intensity and SES, remoteness,
and health service usage. The more disadvantaged and remotely located the
population, the higher the health service usage during HWs. Our study also found
that some population groups and locations were resilient to extreme heat. We
produced a mapping tool, which indicated geographic areas throughout WA with
various vulnerability and resilience levels to HW. The findings from this study
will allow local government, community service organizations, and agencies in
health, housing, and education to better identify and understand the degree of
vulnerability to HW throughout the state, better target preparatory strategies,
and allocate limited resources to those most in need.
PMID- 28421179
TI - Synergy-Based Bilateral Port: A Universal Control Module for Tele-Manipulation
Frameworks Using Asymmetric Master-Slave Systems.
AB - Endowing tele-manipulation frameworks with the capability to accommodate a
variety of robotic hands is key to achieving high performances through permitting
to flexibly interchange the end-effector according to the task considered. This
requires the development of control policies that not only cope with asymmetric
master-slave systems but also whose high-level components are designed in a
unified space in abstraction from the devices specifics. To address this dual
challenge, a novel synergy port is developed that resolves the kinematic,
sensing, and actuation asymmetries of the considered system through generating
motion and force feedback references in the hardware-independent hand postural
synergy space. It builds upon the concept of the Cartesian-based synergy matrix,
which is introduced as a tool mapping the fingertips Cartesian space to the
directions oriented along the grasp principal components. To assess the
effectiveness of the proposed approach, the synergy port has been integrated into
the control system of a highly asymmetric tele-manipulation framework, in which
the 3-finger hand exoskeleton HEXOTRAC is used as a master device to control the
SoftHand, a robotic hand whose transmission system relies on a single motor to
drive all joints along a soft synergistic path. The platform is further enriched
with the vision-based motion capture system Optitrack to monitor the 6D
trajectory of the user's wrist, which is used to control the robotic arm on which
the SoftHand is mounted. Experiments have been conducted with the humanoid robot
COMAN and the KUKA LWR robotic manipulator. Results indicate that this bilateral
interface is highly intuitive and allows users with no prior experience to reach,
grasp, and transport a variety of objects exhibiting very different shapes and
impedances. In addition, the hardware and control solutions proved capable of
accommodating users with different hand kinematics. Finally, the proposed control
framework offers a universal, flexible, and intuitive interface allowing for the
performance of effective tele-manipulations.
PMID- 28421180
TI - Usability Evaluations of a Wearable Inertial Sensing System and Quality of
Movement Metrics for Stroke Survivors by Care Professionals.
AB - BACKGROUND: Inertial motion capture systems are used in many applications such as
measuring the movement quality in stroke survivors. The absence of clinical
effectiveness and usability evidence in these assistive technologies into
rehabilitation has delayed the transition of research into clinical practice.
Recently, a new inertial motion capture system was developed in a project, called
INTERACTION, to objectively measure the quality of movement (QoM) in stroke
survivors during daily-life activity. With INTERACTION, we are to be able to
investigate into what happens with patients after discharge from the hospital.
Resulting QoM metrics, where a metric is defined as a measure of some property,
are subsequently presented to care professionals. Metrics include for example:
reaching distance, walking speed, and hand distribution plots. The latter shows a
density plot of the hand position in the transversal plane. The objective of this
study is to investigate the opinions of care professionals in using these metrics
obtained from INTERACTION and its usability. METHODS: By means of a semi
structured interview, guided by a presentation, presenting two patient reports.
Each report includes several QoM metric (like reaching distance, hand position
density plots, shoulder abduction) results obtained during daily-life
measurements and in clinic and were evaluated by care professionals not related
to the project. The results were compared with care professionals involved within
the INTERACTION project. Furthermore, two questionnaires (5-point Likert and open
questionnaire) were handed over to rate the usability of the metrics and to
investigate if they would like such a system in their clinic. RESULTS: Eleven
interviews were conducted, where each interview included either two or three care
professionals as a group, in Switzerland and The Netherlands. Evaluation of the
case reports (CRs) by participants and INTERACTION members showed a high
correlation for both lower and upper extremity metrics. Participants were most in
favor of hand distribution plots during daily-life activities. All participants
mentioned that visualizing QoM of stroke survivors over time during daily-life
activities has more possibilities compared to current clinical assessments. They
also mentioned that these metrics could be important for self-evaluation of
stroke survivors. DISCUSSION: The results showed that most participants were able
to understand the metrics presented in the CRs. For a few metrics, it remained
difficult to assess the underlying cause of the QoM. Hence, a combination of
metrics is needed to get a better insight of the patient. Furthermore, it remains
important to report the state (e.g., how the patient feels), its surroundings
(outside, inside the house, on a slippery surface), and detail of specific
activities (does the patient grasps a piece of paper or a heavy cooking pan but
also dual tasks). Altogether, it remains a questions how to determine what the
patient is doing and where the patient is doing his or her activities.
PMID- 28421178
TI - Applying Precision Public Health to Prevent Preterm Birth.
AB - Preterm birth (PTB) is one of the major health-care challenges of our time. Being
born too early is associated with major risks to the child with potential for
serious consequences in terms of life-long disability and health-care costs.
Discovering how to prevent PTB needs to be one of our greatest priorities. Recent
advances have provided hope that a percentage of cases known to be related to
risk factors may be amenable to prevention; but the majority of cases remain of
unknown cause, and there is little chance of prevention. Applying the principle
of precision public health may offer opportunities previously unavailable.
Presented in this article are ideas that may improve our abilities in the fields
of studying the effects of migration and of populations in transition, public
health programs, tobacco control, routine measurement of length of the cervix in
mid-pregnancy by ultrasound imaging, prevention of non-medically indicated late
PTB, identification of pregnant women for whom treatment of vaginal infection may
be of benefit, and screening by genetics and other "omics." Opening new research
in these fields, and viewing these clinical problems through a prism of precision
public health, may produce benefits that will affect the lives of large numbers
of people.
PMID- 28421181
TI - MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive
Breast Cancer.
AB - Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of
monocarboxylates such as lactate and pyruvate and a marker of mitochondrial
metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for
catabolite uptake from the tumor microenvironment to support mitochondrial
metabolism. We studied the protein expression of MCT1 in a broad group of breast
invasive ductal carcinoma specimens to determine its association with breast
cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by
immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor
bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen
receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were
human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were
triple negative breast cancers (TNBC). MCT1 expression was quantified by digital
pathology with Aperio software. The intensity of the staining was measured on a
continuous scale (0-black to 255-bright white) using a co-localization algorithm.
Statistical analysis was performed using a linear mixed model. Results: High MCT1
expression was more commonly found in TNBC compared to ER+ and/or PR+ and
compared to HER-2+ (p < 0.001). Tumors with an in-situ component were less likely
to stain strongly for MCT1 (p < 0.05). High nuclear grade was associated with
higher MCT1 staining (p < 0.01). Higher T stage tumors were noted to have a
higher expression of MCT1 (p < 0.05). High MCT1 staining in cancer cells was
associated with shorter progression free survival, increased risk of recurrence,
and larger size independent of TNBC status (p < 0.05). Conclusion: MCT1
expression, which is a marker of high catabolite uptake and mitochondrial
metabolism, is associated with recurrence in breast invasive ductal carcinoma.
MCT1 expression as quantified with digital image analysis may be useful as a
prognostic biomarker and to design clinical trials using MCT1 inhibitors.
PMID- 28421182
TI - TGF-beta1 Pretreatment Improves the Function of Mesenchymal Stem Cells in the
Wound Bed.
AB - The wound healing process initiates after injury to a tissue and involves a
series of orchestrated events to minimize the invasion of foreign matters such as
bacteria and efficiently regenerate the damaged tissue. A variety of cells must
be recruited to the tissue during wound healing. However, this process is
severely disrupted in patients suffering from chronic illness, including
diabetes, leading to impaired healing or non-healing wounds. Current avenues of
treatment include negative-pressure therapy, wound debridement, growth factor
replacement, and cell-based therapies. Among these therapies, mesenchymal stem
cells (MSCs) delivery to the wound holds a very high promise due to the innate
abilities of MSCs that include immunogenicity, plasticity, and self-renewal. Bone
marrow derived MSCs have been shown to promote more rapid wound healing by
increased cytokine production in diabetic mice. However, the lack of
understanding of the mechanical and chemical interaction of the transplanted MSCs
with the factors present in the regenerative niches limits their efficacy in the
wound bed. In this study, we sought to understand how the changes in MSC
biochemical and biophysical properties can affect their function in vitro and in
vivo. We demonstrate that pretreatment of MSCs with the mechano-stimulatory
soluble factor transforming growth factor (TGF-beta1), which is highly expressed
in injury sites, improves wound closure in a syngeneic murine wound model. This
improved wound closure correlated with increased invasion into the wound bed. In
vitro studies demonstrated that TGF-beta1 pretreatment expedited wound closure by
increasing adhesion, traction force, and migration even after removal of the
stimulus. Furthermore, this response was mediated by the cytoskeletal protein
focal adhesion kinase. Taken together, this study suggests that defined chemical
stimuli can benefit site specific adaptability of MSCs to improve their function
and therapeutic usefulness.
PMID- 28421184
TI - The Proteasomal ATPases Use a Slow but Highly Processive Strategy to Unfold
Proteins.
AB - All domains of life have ATP-dependent compartmentalized proteases that sequester
their peptidase sites on their interior. ATPase complexes will often associate
with these compartmentalized proteases in order to unfold and inject substrates
into the protease for degradation. Significant effort has been put into
understanding how ATP hydrolysis is used to apply force to proteins and cause
them to unfold. The unfolding kinetics of the bacterial ATPase, ClpX, have been
shown to resemble a fast motor that traps unfolded intermediates as a strategy to
unfold proteins. In the present study, we sought to determine if the proteasomal
ATPases from eukaryotes and archaea exhibit similar unfolding kinetics. We found
that the proteasomal ATPases appear to use a different kinetic strategy for
protein unfolding, behaving as a slower but more processive and efficient
translocation motor, particularly when encountering a folded domain. We expect
that these dissimilarities are due to differences in the ATP binding/exchange
cycle, the presence of a trans-arginine finger, or the presence of a threading
ring (i.e., the OB domain), which may be used as a rigid platform to pull folded
domains against. We speculate that these differences may have evolved due to the
differing client pools these machines are expected to encounter.
PMID- 28421183
TI - Organ-to-Organ Communication: A Drosophila Gastrointestinal Tract Perspective.
AB - The long-term maintenance of an organism's homeostasis and health relies on the
accurate regulation of organ-organ communication. Recently, there has been
growing interest in using the Drosophila gastrointestinal tract to elucidate the
regulatory programs that underlie the complex interactions between organs. Data
obtained in this field have dramatically improved our understanding of how organ
organ communication contributes to the regulation of various aspects of the
intestine, including its metabolic and physiological status. However, although
research uncovering regulatory programs associated with interorgan communication
has provided key insights, the underlying mechanisms have not been extensively
explored. In this review, we highlight recent findings describing gut-neighbor
and neighbor-neighbor communication models in adults and larvae, respectively,
with a special focus on how a range of critical strategies concerning continuous
interorgan communication and adjustment can be used to manipulate different
aspects of biological processes. Given the high degree of similarity between the
Drosophila and mammalian intestinal epithelia, it can be anticipated that further
analyses of the Drosophila gastrointestinal tract will facilitate the discovery
of similar mechanisms underlying organ-organ communication in other mammalian
organs, such as the human intestine.
PMID- 28421185
TI - Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota
Transplantation for Recurrent Clostridium difficile Infection in a Pediatric
Heart Transplant Patient.
AB - The microbiome is increasingly recognized as an important influence on human
health and many of the comorbidities that affect patients after solid organ
transplantation (SOT) have been shown to involve changes in gut bacterial
populations. Thus, microbiome changes in an individual patient may have important
health implications after SOT but this area remains understudied. We describe
changes in the composition of the fecal microbiome from a pediatric heart
transplant recipient before and >2.5 years after he underwent repeated fecal
microbiota transplantation (FMT) for recurrent Clostridium difficile infection
(CDI). With both documented episodes of CDI, there was marked loss of bacterial
diversity with overgrowth of Proteobacteria (>98.9% of phyla identified)
associated with symptomatic colitis that was corrected after FMT. We hypothesize
that a second CDI occurring after FMT was related to incomplete restoration of
normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes
and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae. Following
the second FMT, there was a gradual shift in gut bacterial composition coincident
with the recipient developing lymphonodular hyperplasia of the colon and painless
hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF).
This case documents dynamic changes in the bacterial microbiome after FMT and
suggests that MMF may influence the gut microbiome with consequences for the
patient.
PMID- 28421186
TI - Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and
Canine Mass Vaccination against Rabies in N'Djamena, Chad.
AB - Rabies claims approximately 59,000 human lives annually and is a potential risk
to 3.3 billion people in over 100 countries worldwide. Despite being fatal in
almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most
common vector, and the timely administration of post-exposure prophylaxis (PEP)
to exposed victims. For the control and prevention of human rabies in N'Djamena,
the capital city of Chad, a free mass vaccination campaign for dogs was organized
in 2012 and 2013. The campaigns were monitored by parallel studies on the
incidence of canine rabies based on diagnostic testing of suspect animals and the
incidence of human bite exposure recorded at selected health facilities. Based on
the cost description of the campaign and the need for PEP registered in health
centers, three cost scenarios were compared: cumulative cost-efficiency of (1)
PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and
maximal communication between human health and veterinary workers (One Health
communication). Assuming ideal One Health communication, the cumulative
prospective cost of dog vaccination and PEP break even with the cumulative
prospective cost of PEP alone in the 10th year from the start of the calculation
(2012). The cost efficiency expressed in cost per human exposure averted is much
higher with canine vaccination and One Health communication than with PEP alone.
As shown in other studies, our cost-effectiveness analysis highlights that canine
vaccination is financially the best option for animal rabies control and rabies
prevention in humans. This study also provides evidence of the beneficial effect
of One Health communication. Only with close communication between the human and
animal health sectors will the decrease in animal rabies incidence be translated
into a decline for PEP. An efficiently applied One Health concept would largely
reduce the cost of PEP in resource poor countries and should be implemented for
zoonosis control in general.
PMID- 28421187
TI - Subset-Specific Expression of Toll-Like Receptors by Bovine Afferent Lymph
Dendritic Cells.
AB - Within the ruminant system, several possibilities exist to generate dendritic
cells migrating out from the tissue into the regional draining lymph nodes as
afferent lymph dendritic cells (ALDCs). Here, we analyzed toll-like receptor
(TLR) 1-10 mRNA expression by using quantitative real-time PCR in highly purified
subsets of bovine ALDC. As TLR expression may be influenced by pathogens or
vaccines and their adjuvant, it is necessary to understand what TLRs are
expressed in a steady-state system to elucidate specific differences and to
potentially optimize targeted vaccines. In this study, we have assessed the TLR
expression profiles of the four main bovine ALDC subsets [cDC1 and cDC2 (subsets
2-4)]. We demonstrate differences in TLR expression between the four subsets that
may reflect the ability of these cells to respond to different pathogens or to
respond to adjuvants.
PMID- 28421188
TI - Pulmonary arteriovenous malformations: evidence of physician under-education.
AB - PAVMs pose unique management challenges; publication patterns indicate their
importance remains poorly recognised http://ow.ly/7iIT304WYl2.
PMID- 28421189
TI - Optic Nerve Sheath Diameter Ultrasound Evaluation in Intensive Care Unit:
Possible Role and Clinical Aspects in Neurological Critical Patients' Daily
Monitoring.
AB - Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable,
noninvasive sonographic marker of intracranial hypertension. Aim of the study was
to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical
patients, to early identify malignant intracranial hypertension in patients with
brain death (BD). Methods. Data from ultrasound ONSD evaluation have been
retrospectively analyzed in 21 sedated critical patients with neurological
diseases who, during their clinical course, developed BD. 31 nonneurological
controls were used for standard ONSD reference. Results. Patients with
neurological diseases, before BD, showed higher ONSD values than control group
(CTRL: RT 0.45 +/- 0.03 cm; LT 0.45 +/- 0.02 cm; pre-BD: RT 0.54 +/- 0.02 cm; LT
0.55 +/- 0.02 cm; p < 0.000) even without intracranial hypertension, evaluated
with invasive monitoring. ONSD was further significantly markedly increased in
respect to the pre-BD evaluation in neurocritical patients after BD, with mean
values above 0.7 cm (RT 0.7 +/- 0.02 cm; LT 0.71 +/- 0.02 cm; p < 0.000), with a
corresponding dramatic raise in intracranial pressure. Logistic regression
analysis showed a strong correlation between ONSD and ICP (R 0,895, p < 0.001).
Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be
performed with a minimal training. Routine ONSD daily monitoring could be of help
in Intensive Care Units when invasive intracranial pressure monitoring is not
available, to early recognize intracranial hypertension and to suspect BD in
neurocritical patients.
PMID- 28421190
TI - First-Trimester Crown-Rump Length and Embryonic Volume of Fetuses with Structural
Congenital Abnormalities Measured in Virtual Reality: An Observational Study.
AB - Background. With the introduction of three-dimensional (3D) ultrasound it has
become possible to measure volumes. The relative increase in embryonic volume
(EV) is much larger than that of the crown-rump length (CRL) over the same time
period. We examined whether EV is a better parameter to determine growth
restriction in fetuses with structural congenital abnormalities. Study Design,
Subjects, and Outcome Measures. CRL and EV were measured using a Virtual Reality
(VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses
diagnosed with structural congenital abnormalities in the first trimester of
pregnancy (gestational age 7+5 to 14+5 weeks). Measured CRL and EV were converted
to z-scores and to percentages of the expected mean using previously published
reference curves of euploid fetuses. The one-sample t-test was performed to test
significance. Results. The EV was smaller than expected for GA in fetuses with
structural congenital abnormalities (-35% p < 0.001, z-score -1.44 p < 0.001),
whereas CRL was not (-6.43% p = 0.118, z-score -0.43 p = 0.605). Conclusions.
CRL is a less reliable parameter to determine growth restriction in fetuses with
structural congenital abnormalities as compared with EV. By measuring EV, growth
restriction in first-trimester fetuses with structural congenital abnormalities
becomes more evident and enables an earlier detection of these cases.
PMID- 28421191
TI - Prospective Multicentre Study on the Epidemiology and Current Therapeutic
Management of Severe Bronchiolitis in Spain.
AB - Objective. To determine the epidemiology and therapeutic management of patients
with severe acute bronchiolitis (AB) admitted to paediatric intensive care units
(PICUs) in Spain. Design. Descriptive, prospective, multicentre study. Setting.
Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission
to any of the participating PICUs over 1 year. Interventions. Both
epidemiological variables and medical treatment received were recorded. Results.
A total of 262 patients were recruited; 143 were male (54.6%), with median age of
1 month (0-23). Median stay in the PICU was 7 days (1-46). Sixty patients (23%)
received no nebuliser treatment, while the rest received a combination of
inhalation therapies. One-quarter of patients (24.8%) received corticosteroids
and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and
noninvasive ventilation (NIV) was used in 75.6%. Endotracheal intubation was
required in 24.4% of patients. Younger age, antibiotic therapy, and invasive
mechanical ventilation (IMV) were risk factors that significantly increased the
stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised
bronchodilator treatment and corticosteroid therapy. Despite NIV being widely
used in this condition, intubation was required in one-quarter of cases. Younger
age, antibiotic therapy, and IMV were associated with a longer stay in the PICU.
PMID- 28421192
TI - Exercise and Protein Intake: A Synergistic Approach against Sarcopenia.
AB - Sarcopenia, the age-dependent loss of muscle mass and function/strength, is
increasingly recognized as a major risk factor for adverse outcomes in frail
older people. As such, the skeletal muscle is a relevant target for interventions
aimed at preventing or postponing the occurrence of negative health-related
events in late life. The association among physical inactivity, insufficient
intake of energy and protein, and poor muscle health in older adults suggests
that physical exercise and targeted nutritional supplementation may offer
substantial therapeutic gain against sarcopenia and its negative correlates. This
view is supported by observational studies as well as by small-scale clinical
trials. In this review, we summarize the available evidence on the beneficial
effects of behavioral interventions on sarcopenia. We also briefly describe how
the knowledge gathered so far has been used to design the "Sarcopenia and
Physical fRailty IN older people: multicomponenT Treatment strategies" (SPRINTT)
project. The randomized clinical trial conducted within SPRINTT will provide
robust evidence on the effectiveness of exercise and nutrition at preventing
negative outcomes associated with sarcopenia and physical frailty.
PMID- 28421194
TI - Dihydromyricetin Protects against Diabetic Cardiomyopathy in Streptozotocin
Induced Diabetic Mice.
AB - Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic
patients. The present study sought to explore the potential effects of
dihydromyricetin (DHM) on DCM and its possible mechanism. A diabetic model was
induced by intraperitoneal injection of streptozotocin (STZ) in C57BL/6J mice.
Two weeks after the STZ injection, mice were randomly allocated into the
following 4 groups for treatment: the control group (CON), the control treated
with DHM group (CON + DHM), the diabetes group (DM), and the diabetes treated
with DHM group (DM + DHM). DHM was dissolved in distilled water and administered
daily by gavage. For 14 weeks, the CON + DHM group and DM + DHM group were given
a dose of 100 mg/kg/day DHM (Sigma-Aldrich), while the CON and DM groups were
intragastrically given equivalent volumes of distilled water. Assessments and
comparisons were made among the groups based on cardiac function and structural
changes, inflammation factors, markers of oxidative stress, mitochondria
function, apoptosis, and autophagy. The DHM treatment normalized body weight,
preserved cardiac function, attenuated oxidative stress (MDA, SOD, and GSH-Px),
reduced the levels of inflammation factors (IL-6, TNF-alpha), alleviated
pathological changes, improved mitochondrial function (ATP content, CS activity,
and complex Iota/IotaIota/IotaIotaIota/IotaV/V activities), inhibited cardiac
apoptosis, and restored autophagy in diabetic mice. DHM may have a great
therapeutic potential in the treatment of DCM.
PMID- 28421193
TI - Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease.
AB - Prevention of bone fractures is one goal of therapy for patients with chronic
kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney
Disease: Improving Global Outcomes guidelines. CKD patients, including those on
hemodialysis, are at higher risk for fractures and fracture-related death
compared to people with normal kidney function. However, few clinicians focus on
this issue as it is very difficult to estimate bone fragility. Additionally,
uremia-related bone fragility has a more complicated pathological process
compared to osteoporosis. There are many uremia-associated factors that
contribute to bone fragility, including severe secondary hyperparathyroidism,
skeletal resistance to parathyroid hormone, and bone mineralization disorders.
Uremia also aggravates bone volume loss, disarranges microarchitecture, and
increases the deterioration of material properties of bone through abnormal bone
cells or excess oxidative stress. In this review, we outline the prevalence of
fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and
discuss possible factors that exacerbate the mechanical properties of bone.
PMID- 28421195
TI - Role of Demyelination Efficiency within Acellular Nerve Scaffolds during Nerve
Regeneration across Peripheral Defects.
AB - Hudson's optimized chemical processing method is the most commonly used chemical
method to prepare acellular nerve scaffolds for the reconstruction of large
peripheral nerve defects. However, residual myelin attached to the basal laminar
tube has been observed in acellular nerve scaffolds prepared using Hudson's
method. Here, we describe a novel method of producing acellular nerve scaffolds
that eliminates residual myelin more effectively than Hudson's method through the
use of various detergent combinations of sulfobetaine-10, sulfobetaine-16, Triton
X-200, sodium deoxycholate, and peracetic acid. In addition, the efficacy of this
new scaffold in repairing a 1.5 cm defect in the sciatic nerve of rats was
examined. The modified method produced a higher degree of demyelination than
Hudson's method, resulting in a minor host immune response in vivo and providing
an improved environment for nerve regeneration and, consequently, better
functional recovery. A morphological study showed that the number of regenerated
axons in the modified group and Hudson group did not differ. However, the
autograft and modified groups were more similar in myelin sheath regeneration
than the autograft and Hudson groups. These results suggest that the modified
method for producing a demyelinated acellular scaffold may aid functional
recovery in general after nerve defects.
PMID- 28421196
TI - Synthesis of L-Ascorbyl Flurbiprofenate by Lipase-Catalyzed Esterification and
Transesterification Reactions.
AB - The synthesis of L-ascorbyl flurbiprofenate was achieved by esterification and
transesterification in nonaqueous organic medium with Novozym 435 lipase as
biocatalyst. The conversion was greatly influenced by the kinds of organic
solvents, speed of agitation, catalyst loading amount, reaction time, and molar
ratio of acyl donor to L-ascorbic acid. A series of solvents were investigated,
and tert-butanol was found to be the most suitable from the standpoint of the
substrate solubility and the conversion for both the esterification and
transesterification. When flurbiprofen was used as acyl donor, 61.0% of L
ascorbic acid was converted against 46.4% in the presence of flurbiprofen methyl
ester. The optimal conversion of L-ascorbic acid was obtained when the initial
molar ratio of acyl donor to ascorbic acid was 5 : 1. kinetics parameters were
solved by Lineweaver-Burk equation under nonsubstrate inhibition condition. Since
transesterification has lower conversion, from the standpoint of productivity and
the amount of steps required, esterification is a better method compared to
transesterification.
PMID- 28421197
TI - Ginsenoside Rg1 Ameliorates Cigarette Smoke-Induced Airway Fibrosis by
Suppressing the TGF-beta1/Smad Pathway In Vivo and In Vitro.
AB - Small airway fibrosis is a key pathological process accompanying chronic
obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast
transdifferentiation and excessive extracellular matrix deposition. Ginsenoside
Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert
an antifibrotic effect in many tissues. However, little is known about the
underlying mechanism and whether ginsenoside Rg1 can exert an effect on small
airway fibrosis. We investigated the anti-small airway fibrosis effects of
ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats. We found
that ginsenoside Rg1 effectively reduced the degree of pulmonary fibrosis,
decreased the expression of alpha-smooth muscle actin, collagen I, and matrix
metalloproteinase 9, and maintained the ratio of matrix metalloproteinase 9 to
tissue inhibitor of metalloproteinase 1. Importantly, ginsenoside Rg1
significantly attenuated cigarette smoke extract-induced upregulation of
transforming growth factor beta1, TGF-beta receptor I, phospho-Smad2, and phospho
Smad3. In addition, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-beta
receptor I-Smad2/3 inhibitor. Collectively, these results suggest that
ginsenoside Rg1 may suppress cigarette smoke-induced airway fibrosis in pulmonary
fibroblasts and COPD rats by inhibiting the TGF-beta1/Smad signaling pathway.
PMID- 28421198
TI - Identify High-Quality Protein Structural Models by Enhanced K-Means.
AB - Background. One critical issue in protein three-dimensional structure prediction
using either ab initio or comparative modeling involves identification of high
quality protein structural models from generated decoys. Currently, clustering
algorithms are widely used to identify near-native models; however, their
performance is dependent upon different conformational decoys, and, for some
algorithms, the accuracy declines when the decoy population increases. Results.
Here, we proposed two enhanced K-means clustering algorithms capable of robustly
identifying high-quality protein structural models. The first one employs the
clustering algorithm SPICKER to determine the initial centroids for basic K-means
clustering (SK-means), whereas the other employs squared distance to optimize the
initial centroids (K-means++). Our results showed that SK-means and K-means++
were more robust as compared with SPICKER alone, detecting 33 (59%) and 42 (75%)
of 56 targets, respectively, with template modeling scores better than or equal
to those of SPICKER. Conclusions. We observed that the classic K-means algorithm
showed a similar performance to that of SPICKER, which is a widely used algorithm
for protein-structure identification. Both SK-means and K-means++ demonstrated
substantial improvements relative to results from SPICKER and classical K-means.
PMID- 28421200
TI - Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before
and after Exercise.
AB - Purpose. The aim of the present study was to elucidate the metabolic mechanisms
associated with chronic fatigue syndrome (CFS) via an analysis of urine
metabolites prior to and following exercise in a rat model. Methods. A rat model
of CFS was established using restraint-stress, forced exercise, and crowded and
noisy environments over a period of 4 weeks. Behavioral experiments were
conducted in order to evaluate the model. Urine metabolites were analyzed via gas
chromatography-mass spectrometry (GC-MS) in combination with multivariate
statistical analysis before and after exercise. Results. A total of 20
metabolites were detected in CFS rats before and after exercise. Three metabolic
pathways (TCA cycle; alanine, aspartate, and glutamate metabolism; steroid
hormone biosynthesis) were significantly impacted before and after exercise,
while sphingolipid metabolism alone exhibited significant alterations after
exercise only. Conclusion. In addition to metabolic disturbances involving some
energy substances, alterations in steroid hormone biosynthesis and sphingolipid
metabolism were detected in CFS rats. Sphingosine and 21-hydroxypregnenolone may
be key biomarkers of CFS, potentially offering evidence in support of immune
dysfunction and hypothalamic-pituitary-adrenal (HPA) axis hypoactivity in
patients with CFS.
PMID- 28421199
TI - Valproic Acid Protects Primary Dopamine Neurons from MPP+-Induced Neurotoxicity:
Involvement of GSK3beta Phosphorylation by Akt and ERK through the Mitochondrial
Intrinsic Apoptotic Pathway.
AB - Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has
recently shown neuroprotective effects in several neurological diseases,
particularly in Parkinson's disease (PD). The goal of the present study was to
confirm VPA's dose-dependent neuroprotective propensities in the MPP+ model of PD
in primary dopamine (DA) neurons and to investigate the underlying molecular
mechanisms using specific mitogen-activated protein kinases (MAPKs) and
phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors. VPA reversed
MPP+-induced mitochondrial apoptosis and counteracted MPP+-induced extracellular
signal-regulated kinase (ERK) and Akt repression and inhibited glycogen synthase
kinase 3beta (GSK3beta) activation through induction of GSK3beta phosphorylation.
Moreover, inhibitors of the PI3K and MAPK pathways abolished GSK3beta
phosphorylation and diminished the VPA-induced neuroprotective effect. These
findings indicated that VPA's neuroprotective effect in the MPP+-model of PD is
associated with GSK3beta phosphorylation via Akt and ERK activation in the
mitochondrial intrinsic apoptotic pathway. Thus, VPA may be a promising
therapeutic candidate for clinical treatment of PD.
PMID- 28421201
TI - Reconstructive and Regenerative Therapy of Atrophic Jaws with New Implant
Techniques: Preclinical and Clinical Studies.
PMID- 28421203
TI - Novel Computational Approaches and Applications in Cancer Research.
PMID- 28421202
TI - The Interaction between HIV and Intestinal Helminth Parasites Coinfection with
Nutrition among Adults in KwaZulu-Natal, South Africa.
AB - In South Africa few studies have examined the effects of the overlap of HIV and
helminth infections on nutritional status. This cross-sectional study
investigated the interaction between HIV and intestinal helminths coinfection
with nutritional status among KwaZulu-Natal adults. Participants were recruited
from a comprehensive primary health care clinic and stratified based on their
HIV, stool parasitology, IgE, and IgG4 results into four groups: the uninfected,
HIV infected, helminth infected, and HIV-helminth coinfected groups. The
nutritional status was assessed using body mass index, 24-hour food recall, micro
, and macronutrient biochemical markers. Univariate and multivariate multinomial
probit regression models were used to assess nutritional factors associated with
singly and dually infected groups using the uninfected group as a reference
category. Biochemically, the HIV-helminth coinfected group was associated with a
significantly higher total protein, higher percentage of transferrin saturation,
and significantly lower ferritin. There was no significant association between
single or dual infections with HIV and helminths with micro- and macronutrient
deficiency; however general obesity and low micronutrient intake patterns, which
may indicate a general predisposition to micronutrient and protein-energy
deficiency, were observed and may need further investigations.
PMID- 28421204
TI - Diabetic Cardiomyopathy: Current Approach and Potential Diagnostic and
Therapeutic Targets.
AB - Although ischemic heart disease is the major cause of death in diabetic patients,
diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant
entity. Considering that it comprises a variety of mechanisms and effects on
cardiac function, increasing the risk of heart failure and worsening the
prognosis of this patient category, DCM represents an important complication of
diabetes mellitus, with a silent development in its earlier stages, involving
intricate pathophysiological mechanisms, including oxidative stress, defective
calcium handling, altered mitochondrial function, remodeling of the extracellular
matrix, and consequent deficient cardiomyocyte contractility. While DCM is common
in diabetic asymptomatic patients, it is frequently underdiagnosed, due to few
diagnostic possibilities in its early stages. Moreover, since a strategy for
prevention and treatment in order to improve the prognosis of DCM has not been
established, it is important to identify clear pathophysiological landmarks, to
pinpoint the available diagnostic possibilities and to spot potential therapeutic
targets.
PMID- 28421205
TI - The Preferential Impairment of Pupil Constriction Stimulated by Blue Light in
Patients with Type 2 Diabetes without Autonomic Neuropathy.
AB - The main aim of the present paper is to examine whether the pupillary light
reflex (PLR) mediated by intrinsically photosensitive retinal ganglion cells
(ipRGCs) is impaired in type 2 diabetic patients. One hundred and three diabetic
patients without diabetic autonomic neuropathy (DAN) and 42 age-matched controls
underwent a series of detailed neurological examinations. The patients were
stratified into three groups: stage I, no neuropathy; stage II, asymptomatic
neuropathy; stage III, symptomatic but without DAN. The PLR to 470 and 635 nm
light at 20 cd/m2 was recorded. Small fiber neuropathy was assessed by corneal
confocal microscopy and quantifying corneal nerve fiber (CNF) morphology. The 470
nm light induced a stronger and faster PLR than did 635 nm light in all subjects.
The PLR to both lights was impaired equally across all of the diabetic subgroups.
The postillumination pupil response (PIPR) after 470 nm light offset at >=1.7 sec
was attenuated in diabetic patients without differences between subgroups.
Receiver operating characteristic analysis revealed that the PIPR mediated by
ipRGCs in patients with stage II and stage III neuropathy was different from that
of the control subjects. Clinical factors, nerve conduction velocity, and CNF
measures were significantly correlated with PLR parameters with 470 nm light. PLR
kinetics were more impaired by stimulation with blue light than with red light in
diabetic patients without DAN.
PMID- 28421206
TI - The Increased Circulating Plasma Levels of Vascular Endothelial Growth Factor in
Patients with Type 1 Diabetes Do Not Correlate to Metabolic Control.
AB - Aim. To characterize the plasma levels of vascular endothelial growth factor
(VEGF) in type 1 diabetes mellitus (T1D) and its relation to both present and
historical metabolic control and microvascular complications. Methods. Plasma
levels of VEGF and routine clinical parameters were analyzed in 115 patients with
long-standing T1D and 45 healthy controls (HC). All patients were under clinical
routine diabetes treatment at Uppsala University Hospital. Results. The plasma
levels of VEGF were increased by 37% in patients with T1D when compared to HC
(18.2 +/- 0.8 versus 13.2 +/- 1.0 pg/ml, p < 0.001). The levels of VEGF
correlated to insulin needs and BMI but not to present or historical metabolic
control. The levels of VEGF were similar in patients with T1D and microvascular
complications (microalbuminuria and retinopathy) when compared with patients
without microvascular complications. Historical HbA1c levels were found to be the
best predictor for present metabolic control. Conclusion. Circulating plasma
levels of VEGF do not correlate to present or historical metabolic control in
long-standing T1D and the levels are not affected by the presence of
microvascular complications.
PMID- 28421208
TI - Enhancing Tumor Detection in IR-UWB Breast Cancer System.
AB - An ultra-wideband (UWB) microwave system for breast cancer detection is
presented. The proposed system includes monocycle pulse generator, antipodal
Vivaldi antenna, breast model, and calibration algorithm for tumor detection.
Firstly, our pulse generator employs transmission gate in glitch generator to
achieve several advantages such as low power consumption and low ringing level.
Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric
substrate material, and developed antenna element (80 * 80 mm2) features a -10 dB
return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the
phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted
in this layer. Finally, subtract and add algorithm (SAD) is used as a calibration
algorithm in tumor detection system. The proposed system suggested that
horizontal antenna position with 90 degrees between transmitting and receiving
antennas is localized as a suitable antenna position with different rotating
location and a 0.5 cm near to phantom. The mean advantages of this localization
and tracking position around breast is a high received power signal approximately
around mv as a higher recognized signal in tumor detection. Using our proposed
system we can detect tumor in 5 mm diameter.
PMID- 28421207
TI - Detection of Human Papillomavirus Genotypes and Epstein-Barr Virus in
Nasopharyngeal Carcinomas at the Korle-Bu Teaching Hospital, Ghana.
AB - Nasopharyngeal carcinomas (NPC) are endemic in Far East Asia and commonly harbour
Epstein-Barr virus (EBV) which is known to serve as a key oncogenic promoter.
Human papillomavirus (HPV) is known to contribute to the pathogenesis of NPC.
However, in Ghana these two viruses have not been linked to NPC prevalence. This
study was designed to determine the HPV genotypes and EBV involved in NPC tissue
biopsies. A retrospective study design involving 72 formalin-fixed paraffin
embedded tissue (FFPET) samples of NPC from 2006 to 2012 were retrieved from the
Department of Pathology, University of Ghana School of Biomedical and Allied
Health Sciences. Sections were taken for histological analysis and for DNA lysate
preparation. The DNA lysates were subjected to polymerase chain reaction (PCR)
analysis to determine the presence of HPV genotypes and EBV. HPV specific primers
were used to type for fourteen HPV genotypes (HPV-16, 18, 6/11, 31, 33, 35, 44,
42, 43, 45, 56, 52, 58, and 59). Out of the 72 NPC biopsies analyzed by PCR, EBV
DNA was present in 18 (25%) cases and HPV DNA in 14 (19.23%). High risk HPV (HR
HPV) genotypes 18 and 31 were associated with the NPC. There were 3 (4.2%) cases
of coinfection by both viruses. The EBV DNA present in the undifferentiated
variant of the NPC and the histopathology of the NPC in Ghana is similar to the
type described in endemic areas.
PMID- 28421209
TI - Excitation dynamics involving homogeneous multistate interactions: one and two
color VMI and REMPI of HBr.
AB - Velocity map imaging (VMI) data and mass resolved REMPI spectra are
complementarily utilized to elucidate the involvement of homogeneous multistate
interactions in excited state dynamics of HBr. The H1Sigma+(v' = 0) and
E1Sigma+(v' = 1) Rydberg states and the V1Sigma+(v'= m + 7) and V1Sigma+(v'= m +
8) ion-pair states are explored as a function of rotational quantum number in the
two-photon excitation region of 79 100-80 700 cm-1. H+ and Br+ images were
recorded by one- as well as two-color excitation schemes. Kinetic energy release
(KER) spectra and angular distributions were extracted from the data. Strong-to
medium interactions between the E(1) and V(m + 8)/V(m + 7) states on one hand and
the H(0) and V(m + 7)/V(m + 8) states on the other hand were quantified from peak
shifts and intensity analysis of REMPI spectra. The effects of those interactions
on subsequent photoionization and photolytic pathways of HBr were evaluated in
one-color VMI experiments of the H+ and two-color VMI experiments of the Br+
photoproducts.
PMID- 28421210
TI - More accurate depiction of adsorption energy on transition metals using work
function as one additional descriptor.
AB - The reaction mechanism and properties of a catalytic process are primarily
determined by the interactions between reacting species and catalysts. However,
the interactions are often challenging to be experimentally measured, especially
for unstable intermediates. Therefore, it is of significant importance to
establish an exact relationship between chemical-catalyst interactions and
catalyst parameters, which will allow calculation of these interactions and thus
advance their mechanistic understanding. Herein we report the description of
adsorption energy on transition metals by considering both ionic bonding and
covalent bonding contributions and introduce the work function as one additional
responsible parameter. We find that the adsorption energy can be more accurately
described using a two-dimensional (2D) polynomial model, which shows a
significant improvement compared with the current adsorption energy-d-band center
linear correlation. We also demonstrate the utilization of this new 2D polynomial
model to calculate oxygen binding energy of different transition metals to help
understand their catalytic properties in oxygen reduction reactions.
PMID- 28421211
TI - Bioinspired carbide-derived carbons with hierarchical pore structure for the
adsorptive removal of mercury from aqueous solution.
AB - Biosilica of the diatom species Thalassiosira pseudonana is used as hard template
for the synthesis of silicon carbide-derived carbons. The typical species
specific macroporous structure is retained during the nanocasting-chlorine
treatment process and the resulting materials exhibit very high specific surface
areas up to 2300 m2 g-1. Bioinspired carbons show very high capacities in mercury
adsorption from aqueous solution compared to reference materials.
PMID- 28421212
TI - Cp*Co(iii)-catalyzed ortho-amidation of azobenzenes with dioxazolones.
AB - Cp*Co(iii)-catalyzed C-H amidation of azobenzene with dioxazolones has been
developed. The amidation reaction does not require external oxidants and gives
carbon dioxide as the only by-product. Both symmetrical and unsymmetrical
azobenzenes were found to undergo amidation smoothly with broad functional group
tolerance.
PMID- 28421213
TI - Nearest-neighbour nanocrystal bonding dictates framework stability or collapse in
colloidal nanocrystal frameworks.
AB - Block copolymers serve as architecture-directing agents for the assembly of
colloidal nanocrystals into a variety of mesoporous solids. Here we report the
fundamental order-disorder transition in such assemblies, which yield, on one
hand, ordered colloidal nanocrystals frameworks or, alternatively, disordered
mesoporous nanocrystal films. Our determination of the order-disorder transition
is based on extensive image analysis of films after thermal processing. The
number of nearest-nanocrystal neighbours emerges as a critical parameter
dictating assembly outcomes, which is in turn determined by the nanocrystal
volume fraction (fNC). We also identify the minimum fNC needed to support the
structure against collapse.
PMID- 28421214
TI - Hybrid molecular/enzymatic catalytic cascade for complete electro-oxidation of
glycerol using a promiscuous NAD-dependent formate dehydrogenase from Candida
boidinii.
AB - Glycerol is a common fuel considered for bioenergy applications. Computational
docking studies were performed on formate dehydrogenase from Candida boidinii
(cbFDH) that showed that mesoxalate can bind to the buried active site of the
holo form predicting that mesoxalate, a byproduct of glycerol oxidation, may act
as its substrate. Spectroscopic assays and characterization by HPLC and GC/TCD
have shown for the first time that cbFDH can act as a decarboxylase with
mesoxalate. From this assessment, cbFDH was combined with NH2-TEMPO to form a
novel hybrid anode to oxidize glycerol to carbon dioxide at near-neutral pH.
PMID- 28421215
TI - Control of supramolecular nanoassemblies by tuning the interactions of bent
shaped rod-coil molecules.
AB - Rod-coil molecules 1a, 1b and 2a, 2b, consisting of biphenyl and phenyl units
connected by an acetylene bond as the rod segment and oligo(ethylene glycol)
(OEG) as the coil segment, were synthesized and characterized. Molecules 1a and
1b incorporate a butoxy group at the apex of their bent-shaped rigid building
blocks, while both 1b and 2b contain a lateral methyl group between the rod and
coil segments. The self-assembling behavior of these molecules was investigated
using DSC, SAXS, CD, AFM, and TEM in bulk and aqueous solutions. In the bulk
state, 1a self-assembles into oblique columnar structures, whereas 1b,
incorporating butoxy and lateral methyl groups, self-assembles into three
dimensional body-centered tetragonal structures. Molecules 2a and 2b with no
butoxy groups, and 2b incorporating a lateral methyl group, self-assemble into
hexagonal perforated lamellar and oblique columnar structures, respectively. In
dilute aqueous solutions, 1a assembles into tubular nanoassemblies, while 1b self
organizes into micelles and nanoparticles. On the other hand, 2a and 2b
spontaneously aggregate into nanoribbons and nanofibers. Furthermore, CD
experiments together with AFM investigations of 2b indicate the creation of self
organized helical fibers, implying that the lateral methyl group induces the
helical stacking of the rod building block. These results reveal that the butoxy
and lateral methyl groups between the rod and coil segments dramatically
influence the creation of supramolecular nanostructures and morphologies.
PMID- 28421216
TI - Kinetics of crystalline nuclei growth in glassy systems.
AB - In this work, we study crystalline nuclei growth in glassy systems, focusing
primarily on the early stages of the process, during which the size of a growing
nucleus is still comparable with the critical size. On the basis of molecular
dynamics simulation results obtained for two crystallizing glassy systems, we
evaluate the growth laws of the crystalline nuclei and the parameters of the
growth kinetics at temperatures corresponding to deep supercooling; herein, a
statistical treatment of the simulation results is carried out using the mean
first-passage-time method. It is found that for the considered systems at
different temperatures, the crystal growth laws that were rescaled onto the
waiting times of the critically-sized nuclei follow a unified dependence, and can
significantly simplify the theoretical description of the post-nucleation growth
of crystalline nuclei. The evaluated size-dependent growth rates are
characterized by a transition to the steady-state growth regime, which depends on
the temperature and occurs in the glassy systems when the size of a growing
nucleus becomes two-three times larger than the critical size. It is suggested
that the temperature dependencies of the crystal growth rate characteristics
should be considered by using the reduced temperature scale T[combining tilde].
Thus, it is revealed that the scaled values of the crystal growth rate
characteristics (namely, the steady-state growth rate and the attachment rate for
the critically-sized nucleus) as functions of the reduced temperature T[combining
tilde] for glassy systems follow unified power-law dependencies. This finding is
supported by the available simulation results; the correspondence with the
experimental data for the crystal growth rates in glassy systems at temperatures
near the glass transition is also discussed.
PMID- 28421217
TI - Lighting-up breast cancer cells by a near-infrared fluorescent probe based on
KIAA1363 enzyme-targeting.
AB - The first NIR KIAA1363-targeting probe, NB-AX, specifically and instantly
featured an "off-on" switch upon gradual addition of KIAA1363 over all kinds of
other biomolecules, and its detection limit was initially calculated to be 0.58
MUg mL-1 (3delta/k). The probe was also able to be used in ultrafast
distinguishing of breast cancer cells from normal cells in fluorescence imaging
and applied in tissue imaging and tumor imaging in vivo.
PMID- 28421218
TI - Catalytic C-H amination driven by intramolecular ligand-to-nitrene one-electron
transfer through a rhodium(iii) centre.
AB - Werner type six-coordinate rhodium(iii) complexes coordinated by a planar
trianionic ligand and two axial aniline ligands are synthesised. The trianionic
ligand behaves as a redox-active ligand to form a ligand radical species upon one
electron oxidation of the complex. The rhodium(iii) complexes catalyse C-H
amination of external substrates such as xanthene with tosylazide as the nitrene
source. DFT-calculation and kinetic deuterium isotope effects indicate that a di
radical rhodium(iii) complex formed by one-electron transfer from the redox
active ligand to the nitrene group works as a reactive intermediate to induce
aliphatic C-H activation.
PMID- 28421219
TI - Kinetic resolution via supramolecular iminium catalysis: multiactivation enables
the asymmetric synthesis of beta-aryl substituted aldehydes and densely
functionalized cyclohexanes.
AB - The kinetic resolution of beta-aryl substituted 1,7-dioxo compounds with
alpha,beta-unsaturated aldehydes affording enantioenriched beta-aryl substituted
aldehydes as well as densely functionalized cyclohexanes is presented. The two
enantioenriched products were obtained in reasonable yields with high diastereo-
and enantioselectivities under supramolecular iminium catalysis which activates
both the substrates and the reactive intermediates.
PMID- 28421220
TI - A highly selective, colorimetric, and environment-sensitive optical potassium ion
sensor.
AB - Potassium ions (K+) play vital roles in many biological processes and thus highly
selective sensors for K+ are critical for disease diagnosis and health
monitoring. Herein, we report a colorimetric K+ sensor (KS7) in which a
hemicyanine dye was used as a fluorophore and phenylaza-[18]crown-6 lariat ether
(ACLE) was utilized as a K+ ligand. The maximum absorption peak of KS7 shifted
hypsochromically by 77 nm (from 515 to 438 nm) with an isosbestic point at 452 nm
upon the addition of K+ to its aqueous solution accompanied by a color change
from red to yellow. This sensor exhibited a linear response range to K+ from 1 to
200 mM, indicating its wide detection range for cellular, urinary, and
environmental potassium ions. Further, this sensor is solvent-sensitive, implying
its environmental sensitivity. For the demonstration of its applications, we
prepared filter paper-based K+ test strips, which were used to detect K+ in urine
conveniently.
PMID- 28421221
TI - Retraction: Synthesis and facet-dependent photocatalytic activity of BiOBr single
crystalline nanosheets.
AB - Retraction of 'Synthesis and facet-dependent photocatalytic activity of BiOBr
single-crystalline nanosheets' by Wenwen Lin et al., Chem. Commun., 2014, DOI:
10.1039/c3cc41498a
PMID- 28421222
TI - Novel photocatalysts: general discussion.
PMID- 28421223
TI - Selectivity of quantum dot sensitized ZnO nanotube arrays for improved
photocatalytic activity.
AB - In this work, PbS/ZnO, CdS/ZnO and CdSe/ZnO hierarchical heterostructures have
been successfully synthesized by combining water bath and chemical bath
deposition (CBD) methods on indium-doped tin oxide (ITO). Scanning electron
microscopy (SEM) results show that quantum dots (QDs) certainly form on the pre
grown ZnO nanorod (NR) and nanotube (NT) arrays. The amount of QDs capped on ZnO
could be regulated by varying the cycle times. The photocatalytic activity of the
QD-sensitized ZnO is investigated by decomposition of methyl orange (MO) under
irradiation, which show remarkable enhancement compared to bare ZnO. The ZnO NTs
sensitized by PbS QDs have the highest catalytic activity among the three QDs
(PbS, CdS and CdSe QDs). The UV-vis absorption diagrams and the Ct/C0 curves
reveal that 8PbS/ZnO NTs have the highest catalytic activity, which can degrade
MO (20 mg L-1) into a colorless solution within 30 min. Meanwhile, the synthetic
methodology described herein provides an effective approach for fabricating a
variety of photocatalysts. The heterostructured nanomaterials have significant
potential to solve environmental and energy issues.
PMID- 28421224
TI - Chirality-induced helical self-propulsion of cholesteric liquid crystal droplets.
AB - We report the first experimental realization of a chiral artificial microswimmer
exhibiting helical motion without any external fields. We discovered that a
cholesteric liquid crystal (CLC) droplet with a helical director field swims in a
helical path driven by the Marangoni flow in an aqueous surfactant solution. We
also showed that the handedness of the helical path is reversed when that of the
CLC droplet is reversed by replacing the chiral dopant with the enantiomer. In
contrast, nematic liquid crystal (NLC) droplets exhibited ballistic motions.
These results suggest that the helical motion of the CLC droplets is driven by
chiral couplings between the Marangoni flow and rotational motion via the helical
director field of CLC droplets.
PMID- 28421225
TI - Using telephony data to facilitate discovery of clinical workflows.
AB - BACKGROUND: Discovery of clinical workflows to target for redesign using methods
such as Lean and Six Sigma is difficult. VoIP telephone call pattern analysis may
complement direct observation and EMR-based tools in understanding clinical
workflows at the enterprise level by allowing visualization of institutional
telecommunications activity. OBJECTIVE: To build an analytic framework mapping
repetitive and high-volume telephone call patterns in a large medical center to
their associated clinical units using an enterprise unified communications server
log file and to support visualization of specific call patterns using graphical
networks. METHODS: Consecutive call detail records from the medical center's
unified communications server were parsed to cross-correlate telephone call
patterns and map associated phone numbers to a cost center dictionary. Hashed
data structures were built to allow construction of edge and node files
representing high volume call patterns for display with an open source graph
network tool. RESULTS: Summary statistics for an analysis of exactly one week's
call detail records at a large academic medical center showed that 912,386 calls
were placed with a total duration of 23,186 hours. Approximately half of all
calling called number pairs had an average call duration under 60 seconds and of
these the average call duration was 27 seconds. CONCLUSIONS: Cross-correlation of
phone calls identified by clinical cost center can be used to generate graphical
displays of clinical enterprise communications. Many calls are short. The compact
data transfers within short calls may serve as automation or re-design targets.
The large absolute amount of time medical center employees were engaged in VoIP
telecommunications suggests that analysis of telephone call patterns may offer
additional insights into core clinical workflows.
PMID- 28421226
TI - Portable LED-induced autofluorescence spectroscopy for oral cancer diagnosis.
AB - Oral cancer is a serious and growing problem in many developing and developed
countries. To improve the cancer screening procedure, we developed a portable
light-emitting-diode (LED)-induced autofluorescence (LIAF) imager that contains
two wavelength LED excitation light sources and multiple filters to capture ex
vivo oral tissue autofluorescence images. Compared with conventional means of
oral cancer diagnosis, the LIAF imager is a handier, faster, and more highly
reliable solution. The compact design with a tiny probe allows clinicians to
easily observe autofluorescence images of hidden areas located in concave deep
oral cavities. The ex vivo trials conducted in Taiwan present the design and
prototype of the portable LIAF imager used for analyzing 31 patients with 221
measurement points. Using the normalized factor of normal tissues under the
excitation source with 365 nm of the central wavelength and without the bandpass
filter, the results revealed that the sensitivity was larger than 84%, the
specificity was not smaller than over 76%, the accuracy was about 80%, and the
area under curve of the receiver operating characteristic (ROC) was achieved at
about 87%, respectively. The fact shows the LIAF spectroscopy has the
possibilities of ex vivo diagnosis and noninvasive examinations for oral cancer.
PMID- 28421227
TI - Multiple, Fine, Firm Keratotic Papules on the Palms: A Quiz.
PMID- 28421228
TI - Extraordinary Findings in a Case of Self-inflicted Cutaneous Lesions.
PMID- 28421229
TI - Atypical Trigeminal Trophic Syndrome: An Unusual Cause of Facial Ulceration.
PMID- 28421230
TI - Locally Aggressive Trichoblastic Tumours (Low-grade Trichoblastic Carcinomas):
Clinicopathological Analysis and Follow-up.
PMID- 28421231
TI - Periorbital Involvement in Early Stage Mycosis Fungoides.
PMID- 28421232
TI - Clinical Spectrum, Quality of Life, BRAF Mutation Status and Treatment of Skin
Involvement in Adult Langerhans Cell Histiocytosis.
AB - Langerhans cell histiocytosis is a rare histiocytic disorder for which skin
involvement and management are poorly described in adults. The aim of this
retrospective monocentric study in a national reference centre is to describe the
clinical characteristics, quality of life, BRAF mutation status and outcomes of
skin involvement in adult patients with Langerhans cell histiocytosis. Twenty
five patients (14 females, mean age 47 years) were included, with a median follow
up of 33 months (range 4-420 months). Patients experienced poor dermatological
quality of life despite low body surface involvement. BRAFV600 mutations were
detected in 8 of the 18 patients analysed (45%). Eight patients had an associated
malignancy. Several treatment options were used and consisted of surgery, topical
steroids and carmustine, thalidomide, methotrexate, vinblastine and steroids and
cladribine. This study highlights the need to evaluate quality of life and to
screen for associated malignancy in adult patients with Langerhans cell
histiocytosis.
PMID- 28421233
TI - Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with
Gene Polymorphism Suggests a Role in Disease Pathogenesis.
AB - CD93 is involved in angiogenesis and inflammation, both of which are key
processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral
blood mononuclear cells and skin of patients with psoriasis and controls.
Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms
rs2749812 and rs2749817 were assessed in patients with psoriasis compared with
controls and the effect of narrowband ultraviolet B (NB-UVB) treatment on CD93
gene expression was evaluated in the skin of patients with psoriasis. CD93 gene
expression was significantly increased in lesional and non-lesional skin from
patients with psoriasis compared with controls. Immunohistochemistry revealed
CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was
significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment
of patients with psoriasis did not alter skin CD93 gene expression. Increased
protein expression of CD93 psoriatic skin and association with the rs2749817
polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.
PMID- 28421234
TI - The Role of Topical Timolol in the Treatment of Infantile Hemangiomas: A
Systematic Review and Meta-analysis.
AB - To date the efficacy and safety of topical timolol in the treatment of infantile
hemangioma has not been reviewed and analysed systematically. We collated all
published data on the efficacy and safety of topical timolol in the treatment of
infantile hemangioma. A total of 31 studies with 691 patients were included. The
fixed effects pooled estimate of the response rate defined as any improvement
from baseline of infantile hemangioma after treatment with topical timolol was
significant (RR = 8.96; 95% CI 5.07-15.47; heterogeneity test p = 0.99), and the
treatment was overall well tolerated. However, the quality of evidence was low to
moderate. Topical timolol is an effective treatment for small infantile
hemangioma, with no significant adverse effects noted. However, there is still a
need for adequately powered randomised controlled trials.
PMID- 28421235
TI - Koebner Phenomenon in Eosinophilic Granulomatosis with Polyangiitis (Churg
Strauss).
PMID- 28421236
TI - Uncommon Presentation of Scleromyxoedema with a Distribution Pattern Mimicking a
Photodermatosis.
PMID- 28421237
TI - Radiographic interpretation of carpometacarpal arthroplasty: correlation between
radiographic loosening and clinical outcome.
AB - OBJECTIVE: To assess the radiographic appearance and interpretation of loosening
in patients following first carpometacarpal joint pyrohemisphere arthroplasty.
MATERIALS AND METHODS: A retrospective review over a 6-year period was performed
identifying patients with first carpometacarpal pyrohemisphere implants. All
postoperative radiographs were reviewed and compared with clinical information.
Loosening was defined as greater than 1 mm of periprosthetic lucency or
increasing lucency on serial studies. Adverse clinical outcome was defined as
infection, complex regional pain syndrome, subluxation or an inability to return
to activities of daily living. Statistical analysis included Cohen's Kappa
coefficient to measure inter-reader agreement for radiographic interpretation and
the agreement between radiographic loosening and an undesired or adverse clinical
outcome. RESULTS: Thirty-one implants in 26 patients were reviewed. A total of 73
postoperative radiographs were reviewed. The mean age of the study subjects was
58 years. The mean radiographic follow-up was 13 months (range: 1-56). All
arthroplasties were performed for osteoarthritis. Only one repeat surgery was
performed. There was good agreement amongst readers with regard to radiographic
interpretation, but the strength of agreement between radiographic loosening and
adverse clinical outcome was poor. The sensitivity of radiography in predicting
an adverse clinical outcome was 63%, specificity 65%, positive predictive value
39%, and negative predictive value 83%. CONCLUSION: Although radiography may be
useful in the correct clinical context, it should not be utilized as the sole
predictor of adverse clinical outcomes following carpometacarpal arthroplasty.
PMID- 28421238
TI - The impact of low education and poor health on unemployment varies by work life
stage.
AB - OBJECTIVES: The aim of this study is to examine associations and interactions of
education, and physical and mental health with unemployment in early, mid, and
late work life. METHODS: This cross-sectional study uses data from 69,118
respondents from Lifelines. Health status was measured with the RAND-36,
education was self-reported, and participants working <12 h per week or
indicating to be unemployed were considered unemployed. The relative excess risk
due to interaction (RERI) was calculated to measure interaction on the additive
scale. RESULTS: Interactions of low education and poor mental health were found
in early [RERI: 2.14; 95% confidence interval (CI): 0.63, 3.65], mid (1.41; 0.61,
2.20) and late (0.63; 0.09, 1.17) work life. Interaction between low education
and poor physical health was only found in mid-work life (1.27; 0.61, 1.93).
CONCLUSIONS: Low education and poor physical and mental health exacerbate each
other's impact on unemployment varying by work life stage. Policies addressing
unemployment may become more effective if they better account for the physical
and mental health status of adults in certain stages of their work life.
PMID- 28421239
TI - Weight-bearing recommendations after operative fracture treatment-fact or
fiction? Gait results with and feasibility of a dynamic, continuous
pedobarography insole.
AB - PURPOSE: Rehabilitation after lower-extremity fractures is based on the
physicians' recommendation for non-, partial-, or full weight-bearing. Clinical
studies rely on this assumption, but continuous compliance or objective loading
rates are unknown. The purpose of this study was to determine the compliance to
weight-bearing recommendations by introducing a novel, pedobarography system
continuously registering postoperative ground forces into ankle, tibial shaft and
proximal femur fracture aftercare and test its feasibility for this purpose.
METHODS: In this prospective, observational study, a continuously measuring
pedobarography insole was placed in the patients shoe during the immediate post
operative aftercare after ankle, tibial shaft and intertrochanteric femur
fractures. Weight-bearing was ordered as per the institutional standard and
controlled by physical therapy. The insole was retrieved after a maximum of six
weeks (28 days [range 5-42 days]). Non-compliance was defined as a failure to
maintain, or reach the ordered weight-bearing within 30%. RESULTS: Overall 30
patients were included in the study. Fourteen (47%) of the patients were
compliant to the weight-bearing recommendations. Within two weeks after surgery
patients deviated from the recommendation by over 50%. Sex, age and weight did
not influence the performance (p > 0.05). Ankle fracture patients (partial weight
bearing) showed a significantly increased deviation from the recommendation (p =
0.01). CONCLUSIONS: Our study results show that, despite physical therapy
training, weight-bearing compliance to recommended limits was low. Adherence to
the partial weight-bearing task was further decreased over time. Uncontrolled
weight-bearing recommendations should thus be viewed with caution and carefully
considered as fiction. The presented insole is feasible to determine weight
bearing continuously, could immediately help define real-time patient behaviour
and establish realistic, individual weight-bearing recommendations.
PMID- 28421241
TI - Effect of methyl-beta-cyclodextrin on gene expression in microbial conversion of
phytosterol.
AB - Modified beta-cyclodextrins are widely used for the enhancement of microbial
conversions of lipophilic compounds such as steroids. Multiple mechanisms of
cyclodextrin-mediated enhancement of phytosterol bioconversion by mycobacteria
had previously been shown to include steroid solubilization, alterations in the
cell wall permeability for both steroids and nutrients, facilitation of protein
leaking, and activity suppression of some steroid-transforming enzymes.In this
work, we studied whether cyclodextrins might affect expression of the genes
involved in the steroid catabolic pathway. Phytosterol bioconversion with 9alpha
hydroxy-androst-4-ene-3,17-dione accumulation by Mycobacterium sp. VKM Ac-1817D
in the presence of methylated beta-cyclodextrin (MCD) was investigated. RNA
sequencing of the whole transcriptomes in different combinations of phytosterol
and MCD showed a similar expression level of the steroid catabolism genes related
to the KstR-regulon and was responsible for side chain and initial steps of
steroid core oxidation; whereas, induction levels of the genes related to the
KstR2-regulon were attenuated in the presence of MCD in this strain. The data
were attenuated with quantitative real-time PCR.The results contribute to the
understanding of cyclodextrin effects on microbial steroid conversion and provide
a basis for the use of cyclodextrins as expression enhancers for studies of
sterol catabolism in actinobacteria.
PMID- 28421240
TI - A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel
and prednisone versus docetaxel and prednisone alone in castration-resistant
prostate cancer (CRPC) metastatic to bone; the Taxium II trial.
AB - BACKGROUND: Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for
palliation of metastatic bone pain. We investigated whether the addition of
rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in
patients with CRPC. METHODS: Patients with progressive CRPC and osteoblastic bone
metastases were randomised for first-line docetaxel 75 mg/m2 3-weekly plus
prednisone with or without 2 injections of rhenium-188-HEDP after the third (40
MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was
progression-free survival (PFS), defined as either PSA, radiographic or clinical
progression. Patients were stratified by extent of bone metastases and hospital.
RESULTS: Forty-two patients were randomised for standard treatment and 46
patients for combination therapy. Median number of cycles of docetaxel was 9 in
the control group and 8 in the experimental group. Median follow-up was 18.4
months. Two patients from the experimental group did not start treatment after
randomisation. In the intention to treat analysis no differences in PFS, survival
and PSA became apparent between the two groups. In an exploratory per-protocol
analysis median overall survival was significantly longer in the experimental
group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months
(95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline
phosphatase >220U/L was significantly better with combination treatment (9.0
months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005).
As expected, thrombocytopenia (grade I/II) was reported more frequently in the
experimental group (25% versus 0%). CONCLUSION: Combined treatment with rhenium
188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed
survival benefit in the per-protocol analysis warrants further studies in the
combined treatment of chemotherapy and radiopharmaceuticals.
PMID- 28421242
TI - CT features of hepatic metastases from hepatoid adenocarcinoma.
AB - PURPOSE: The purpose of this study was to report the imaging presentation of
hepatic metastases from hepatoid adenocarcinoma (HAC). METHODS: We
retrospectively identified 11 patients (10 men and 1 woman; median age 66) with
HAC liver metastasis who underwent contrast-enhanced computed tomography (CT)
which included arterial phase and portal venous phase. Two radiologists analyzed
the imaging parameters, which included the enhancement pattern on arterial and
portal phase images, necrosis, venous thrombi, and overall imaging diagnosis, and
arrived at a consensus. RESULTS: On arterial phase, the liver lesions had global
hyper-enhancement (n = 0), heterogeneous hyper-enhancement (63.6%; n = 7/11),
peripheral hyper-enhancement (n = 0), iso-enhancement (n = 0/11), or hypo
enhancement (36.4%; n = 4/11). On portal venous phase, homogenous hypo
enhancement (18.2%; n = 2/11) and heterogenous hypo-enhancement (81.8%; n = 9/11)
were observed. Venous thromboses occurred in four patients (36.4%; n = 4/11). The
overall imaging diagnoses were "HCC-like" in seven patients (63.6%; n = 7/11),
"indeterminable" in 1 patient (9.1%; n = 1/11), and "HCC-unlike" in three
patients (27.3%; n = 3/11). CONCLUSIONS: The imaging features of HAC liver
metastasis were varied. Arterial phase enhancement coupled with venous phase
washout (resembling HCC imaging features) was a major finding, but arterial phase
hypo-enhancement (distinct from HCC imaging features) was also frequently
encountered.
PMID- 28421243
TI - Assessment of 70-keV virtual monoenergetic spectral images in abdominal CT
imaging: A comparison study to conventional polychromatic 120-kVp images.
AB - PURPOSE: To evaluate the image quality of 70-keV virtual monoenergetic (monoE)
abdominal CT images compared to 120-kVp polychromatic images generated from a
spectral detector CT (SDCT) scanner. METHODS: This prospective study included
generation of a 120-kVp polychromatic dataset and a 70-keV virtual monoE dataset
after a single contrast-enhanced CT acquisition on a SDCT scanner (Philips
Healthcare) during portal venous phase. The attenuation values (HU), noise,
signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured in
the liver, spleen, pancreas, kidney, aorta, portal vein, and muscle. The
subjective image quality including noise, soft tissue contrast, sharpness, and
overall image quality were graded on a 5-point Likert scale by two radiologists
independently (1-worst image quality, 5-best image quality). Statistical analysis
was performed using paired sample t test and Fleiss's Kappa. RESULTS: Fifty-five
patients (54.3 +/- 16.8 y/o; 28 M, 27 F) were recruited. The noise of target
organs was significantly lower in virtual monoE images in comparison to
polychromatic images (p < 0.001). The SNR and CNR were significantly higher in
virtual monoE images (p < 0.001 for both). Subjective image quality of 70-keV
virtual monoE images was significantly better (p < 0.001) for all evaluated
parameters. Median scores for all subjective parameters were 3.0 versus 4.0 for
polychromatic vs virtual monoE images, respectively. The inter-reader agreement
for overall image quality was good (Kappa were 0.767 and 0.762 for polychromatic
and virtual monoE images, respectively). CONCLUSION: In abdominal imaging, 70-keV
virtual monoE CT images demonstrated significantly better noise, SNR, CNR, and
subjective score compared to conventional 120-kVp polychromatic images.
PMID- 28421244
TI - Texture analysis as a radiomic marker for differentiating renal tumors.
AB - PURPOSE: To evaluate the utility of texture analysis for the differentiation of
renal tumors, including the various renal cell carcinoma subtypes and oncocytoma.
MATERIALS AND METHODS: Following IRB approval, a retrospective analysis was
performed, including all patients with pathology-proven renal tumors and an
abdominal computed tomography (CT) examination. CT images of the tumors were
manually segmented, and texture analysis of the segmented tumors was performed. A
support vector machine (SVM) method was also applied to classify tumor types.
Texture analysis results were compared to the various tumors and areas under the
curve (AUC) were calculated. Similar calculations were performed with the SVM
data. RESULTS: One hundred nineteen patients were included. Excellent
discriminators of tumors were identified among the histogram-based features
noting features skewness and kurtosis, which demonstrated AUCs of 0.91 and 0.93
(p < 0.0001), respectively, for differentiating clear cell subtype from
oncocytoma. Histogram feature median demonstrated an AUC of 0.99 (p < 0.0001) for
differentiating papillary subtype from oncocytoma and an AUC of 0.92 for
differentiating oncocytoma from other tumors. Machine learning further improved
the results achieving very good to excellent discrimination of tumor subtypes.
The ability of machine learning to distinguish clear cell subtype from other
tumors and papillary subtype from other tumors was excellent with AUCs of 0.91
and 0.92, respectively. CONCLUSION: Texture analysis is a promising non-invasive
tool for distinguishing renal tumors on CT images. These results were further
improved upon application of machine learning, and support the further
development of texture analysis as a quantitative biomarker for distinguishing
various renal tumors.
PMID- 28421245
TI - Research in community-acquired pneumonia: the next steps.
PMID- 28421246
TI - Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT):
a randomised, blinded, placebo-controlled trial.
AB - PURPOSE: The aim of the INSTINCT trial was to assess the effect of intravenous
polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported
physical function in intensive care unit (ICU) patients with necrotising soft
tissue infection (NSTI). METHODS: We randomised 100 patients with NSTI 1:1 to
masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of
0.9% saline once daily for the first 3 days of ICU admission. The primary outcome
was the physical component summary (PCS) score of the 36-item short form health
survey (SF-36) 6 months after randomisation; patients who had died were given the
lowest possible score (zero). RESULTS: Of the 100 patients randomised, 87 were
included in the intention-to-treat analysis of the PCS score, 42 patients (84%)
in the IVIG group and 45 patients (90%) in the placebo group. The two
intervention groups had similar baseline characteristics with the exception of
IVIG use before randomisation (1 dose was allowed) and rates of acute kidney
injury. Median PCS scores were 36 (interquartile range 0-43) in the group
assigned to IVIG and 31 (0-47) in the group assigned to placebo (mean adjusted
difference 1 (95% confidence interval -7 to 10), p = 0.81). The result was
supported by analyses adjusted for baseline prognostics, those in the per
protocol populations, in the subgroups (site of NSTI) and those done post hoc
adjusted for IVIG use before randomisation. CONCLUSIONS: In ICU patients with
NSTI, we observed no apparent effects of adjuvant IVIG on self-reported physical
functioning at 6 months. TRIAL REGISTRATION: NCT02111161.
PMID- 28421247
TI - [Rare Diseases].
PMID- 28421248
TI - Indications for cellular migration from the central nervous system to its
draining lymph nodes in CD11c-GFP+ bone-marrow chimeras following EAE.
AB - The concept as to how the brain maintains its immune privilege has initially been
based on observations that it is lacking classical lymph vessels and later, the
absence of dendritic cells (DC). This view has been challenged by several groups
demonstrating drainage/migration of injected tracers and cells into cervical
lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of
various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green
fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of
CD11c+ cells, a main DC marker, within the brain parenchyma. Since injecting
tracers or cells may cause barrier artefacts, we have now transplanted wild type
(wt)-bone marrow (BM) to lethally irradiated CD11c-DTR-GFP tg mice to restrict
the CD11c-DTR-GFP+ population to the brain and induced experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We observed
ramified GFP+ cells in the olfactory bulb, the cribriform plate, the nasal mucosa
and superficial CLNs. We measured a significant increase of host gfp genomic DNA
(gDNA) levels in lymph nodes (LNs) previously described as draining stations for
the central nervous system (CNS). Using flow cytometry analysis, we observed an
increase of the percentage of CD11c-GFP+ cells in brain parenchyma in the course
of EAE which is most likely due to an up-regulation of CD11c of resident
microglial cells since levels of gfp gDNA did not increase. Our data supports the
hypothesis that brain-resident antigen presenting cells (APC) are capable of
migrating to CNS-draining LNs to present myelin-associated epitopes.
PMID- 28421249
TI - Co-effects of pyrene and nitrate on the activity and abundance of soil
denitrifiers under anaerobic condition.
AB - It has previously been confirmed that polycyclic aromatic hydrocarbons (PAHs)
could be degraded by soil microbes coupling with denitrification, but the
relationships among soil denitrifiers, PAHs, and nitrate under obligate anaerobic
condition are still unclear. Here, co-effects of pyrene and nitrate on the
activity and abundance of soil denitrifiers were investigated through a 45-day
incubation experiment. Two groups of soil treatments with (N30) and without (N0)
nitrate (30 mg kg-1 dry soil) amendment were conducted, and each group contained
three treatments with different pyrene concentrations (0, 30, and 60 mg kg-1 dry
soil denoted as P0, P30, and P60, respectively). The pyrene content, abundances
of denitrification concerning genes (narG, periplasmic nitrate reductase gene;
nirS, cd 1-nitrite reductase gene; nirK, copper-containing nitrite reductase
gene), and productions of N2O and CO2 were measured at day 3, 14, 28, and 45, and
the bacterial community structures in four represented treatments (N0P0, N0P60,
N30P0, and N30P60) were analyzed at day 45. The results indicated that the
treatments with higher pyrene concentration had higher final pyrene removal rates
than the treatments with lower pyrene concentration. Additionally, intensive
emission of N2O was detected in all treatments only at day 3, but a continuous
production of CO2 was measured in each treatment during the incubation. Nitrate
amendment could enhance the activity of soil denitrifiers, and be helpful for
soil microbes to sustain their activity. While pyrene seemed had no influence on
the productions of N2O and CO2, and amendment with pyrene or nitrate both had no
obvious effect on abundances of denitrification concerning genes. Furthermore, it
was nitrate but not pyrene had an obvious influence on the community structure of
soil bacteria. These results revealed that, under anaerobic condition, the
activity and abundance of soil denitrifiers both were insensitive to pyrene, but
nitrate could improve the activity of soil denitrfiers and induce the shifts in
soil bacterial community structure.
PMID- 28421250
TI - Erratum to: CX3CR1 deficiency accelerates the development of retinopathy in a
rodent model of type 1 diabetes.
PMID- 28421252
TI - Altitude Distributions and Source Analysis of OCPs and PCBs in Surface Soils of
Changbai Mountain, Northeast China.
AB - Organochlorine pesticides and polychlorinated biphenyls in surface soils of
Changbai Mountain, Northeastern China, have been quantified by gas chromatography
with electron capture detector and the altitude distributions and possible
pollution sources were analyzed. The concentrations of ?HCHs, ?DDTs and ?7PCBs
were in the range of 3.09-25.6, 0.96-19.4 and 7.32-26.1 ng/g dw, respectively.
The concentration of alpha-HCH, beta-HCH, p,p'-DDT, p,p'-DDE, PCB 101, 138, 153,
and 180 showed increasing trends with altitude. ?7PCBs in surface soils of
Changbai Mountain were significantly higher than that in Chinese background
areas. The concentration of lower volatile PCB isomers showed positive
correlation with altitude. These pollutants may originate from the adjacent
industrial and agricultural areas via atmospheric transport and cold-trapping
effect through wet precipitation. Additional, DDTs may cause a certain potential
ecological risks on birds and soil organisms and the usage of lindane in the
adjacent areas cannot be excluded in Changbai Mountain.
PMID- 28421251
TI - Defining the ultrasound longitudinal natural history of newly diagnosed pediatric
small bowel Crohn disease treated with infliximab and infliximab-azathioprine
combination therapy.
AB - BACKGROUND: Little is known about changes in the imaging appearances of the bowel
and mesentery over time in either pediatric or adult patients with newly
diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha
(anti-TNF-alpha) therapy. OBJECTIVE: To define how bowel ultrasound findings
change over time and correlate with laboratory inflammatory markers in children
who have been newly diagnosed with pediatric small bowel Crohn disease and
treated with infliximab. MATERIALS AND METHODS: We included 28 pediatric patients
treated with infliximab for newly diagnosed ileal Crohn disease who underwent
bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month,
3 months and 6 months after treatment initiation; these patients also had
laboratory testing at baseline, 1 month and 6 months. We used linear mixed models
to compare mean results between visits and evaluate whether ultrasound
measurements changed over time. We used Spearman rank correlation to assess
bivariate relationships. RESULTS: Mean subject age was 15.3+/-2.2 years; 11
subjects were girls (39%). We observed decreases in mean length of disease
involvement (12.0+/-5.4 vs. 9.1+/-5.3 cm, P=0.02), maximum bowel wall thickness
(5.6+/-1.8 vs. 4.7+/-1.7 mm, P=0.02), bowel wall color Doppler signal (1.7+/-0.9
vs. 1.2+/-0.8, P=0.002) and mesenteric color Doppler signal (1.1+/-0.9 vs. 0.6+/
0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab
compared to baseline. All laboratory inflammatory markers decreased at 1 month (P
values<0.0001). There was strong correlation between bowel wall color Doppler
signal and fecal calprotectin (rho=0.710; P<0.0001). Linear mixed models
confirmed that maximum bowel wall thickness (P=0.04), length of disease
involvement (P=0.0002) and bowel wall color Doppler signal (P<0.0001) change over
time in response to infliximab, when adjusted for age, sex, azathioprine therapy,
scanning radiologist and baseline short pediatric Crohn's disease activity index
score. CONCLUSION: The ultrasound appearance of the bowel changes as early as 2
weeks after the initiation of infliximab therapy. There is strong correlation
between bowel wall color Doppler signal and fecal calprotectin.
PMID- 28421253
TI - Levels and Sources of Organochlorine Pesticides in Surface Sediment from Anhui
Reach of Huaihe River, China.
AB - Twenty-two organochlorine pesticides (OCPs) were investigated in Anhui reach of
Huaihe river, China. Seventeen out of 22 OCPs were detected by GC-MS. The mean
concentrations of OCPs followed the order: HCHs > DDTs > HCB > chlordanes >
endosulfans. Levels of total HCHs and total DDTs ranged from 2.54 to 13.91 ng g-1
(mean = 7.52 ng g-1) and 0.016 to 2.54 ng g-1 (mean = 0.45 ng g-1), respectively.
The concentrations of DDTs were lower than those of HCHs. Compared with the other
rivers in China, DDTs and HCHs were relatively lower or similar. Statistical
analysis indicated that the OCPs concentration differences were not insignificant
between upstream, midstream and downstream. The compound compositions suggested
that historical usage of lindane and fresh DDT were the main sources. The
regression analysis indicated that TOC has influence on the levels of HCHs and
little influence on the levels of DDTs in the sediments.
PMID- 28421254
TI - [Scalp disorders].
PMID- 28421255
TI - [Tropical dermatology-relevant disorders of the scalp].
AB - People whose ancestors came from tropical regions present specific structural
characteristics of their skin and hair, including the scalp region. On the one
hand, this is for protection against the challenges of these climatic zones; on
the other hand, this may lead to an enhanced sensitivity against certain
dermatological diseases, either of autoimmune, chronic inflammatory, infectious,
or of mechanical origin. A collection of these are discussed in this article.
PMID- 28421256
TI - Special issue: recognizing the lifetime scientific contributions of Athina
Markou.
PMID- 28421257
TI - Histone deacetylase inhibitors reverse age-related increases in side effects of
haloperidol in mice.
AB - BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced
side effects, and the pharmacodynamic mechanism underlying this phenomenon
remains unclear. We hypothesized that age-related epigenetic alterations lead to
decreased expression and functionality of the dopamine D2 receptor (D2R),
contributing to this susceptibility. METHODS: In this study, we treated young (2
3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist
haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side
effects. In addition, we pretreated separate groups of young and aged mice with
histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275)
and then administered HAL. RESULTS: Our results show that the motor side effects
of HAL are exaggerated in aged mice as compared to young mice and that HDAC
inhibitors are able to reverse the severity of these deficits. HAL-induced motor
deficits in aged mice are associated with an age- and drug-dependent decrease in
striatal D2R protein levels and functionality. Further, histone acetylation was
reduced while histone tri-methylation was increased at specific lysine residues
of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC
inhibitors, particularly VPA, restored striatal D2R protein levels and
functionality and reversed age- and drug-related histone modifications at the
Drd2 promoter. CONCLUSIONS: These results suggest that epigenetic changes at the
striatal Drd2 promoter drive age-related increases in antipsychotic side effect
susceptibility, and HDAC inhibitors may be an effective adjunct treatment
strategy to reduce side effects in aged populations.
PMID- 28421258
TI - [Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation
with cochlear implants. German version].
AB - Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden
hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed
an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebello
pontine angle (CPA), 1 a transotic including the CPA and 1 a multilocular
location. The tumors were removed surgically in 9 patients, whereas 3 patients
opted for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3
underwent labyrinthectomy and cochlear implant (CI) surgery in a single stage
procedure; 1 patient received extended cochleostomy with CI surgery; 3 underwent
partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI
surgery (n = 1) or implantation of electrode dummies for possible later CI
following repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the
internal auditory canal and cerebellopontile angle exhibiting transmodiolar or
transmacular growth were removed by combined translabyrinthine-transotic
resection. For the intracochlear tumors, vestibular function could mostly be
preserved after surgery. In all cases with CI surgery, hearing rehabilitation was
successful, although speech discrimination was limited for the case with subtotal
cochleoectomy. Surgical removal of intracochlear schwannomas via partial or
subtotal cochleoectomy is, in principle, possible with preservation of vestibular
function. In the authors' opinion, radiotherapy of ILS is only indicated in
isolated cases. Provided performed early enough, cochlear implantation after
surgical removal of ILS is an option for auditory rehabilitation, thus
representing-in contrast to the "wait-and-test-and-scan" strategy-a therapeutic
approach.
PMID- 28421259
TI - [Bariatric surgery versus medical therapy in the treatment of obesity].
PMID- 28421260
TI - [Gigantic exophytically growing tumor of the occipital scalp : A complex
diagnostic and reconstructive challenge].
PMID- 28421261
TI - [Positive and negative predictors of long-term results after an osteotomy around
the knee joint].
AB - A frequently asked question in the context of any surgical procedure, including
an osteotomy around the knee joint, is "which parameters are in favor of a
therapeutic success in this special case?" If the analysis of the leg geometry is
in favor of an osteotomy, then the patient must be assessed further, taking into
account the joint status and patient's condition. Positive outcome predictors for
long-term success of an osteotomy around the knee, especially for a valgus
osteotomy at the tibia are a tibial bone varus angle (TBVA) > 3-5 degrees , knee
joint range of motion > 100 degrees flexion, male sex, and a BMI < 30. It is
unclear whether the degree of degeneration of the affected (medial) compartment
is of special relevance. The severity of malalignment, the patient's sex, and
psychopathological comorbidities are not important.
PMID- 28421262
TI - Transanal Endoscopic Operation Versus Conventional Transanal Excision for Rectal
Tumors: Case-Matched Study with Propensity Score Matching.
AB - BACKGROUNDS: Although transanal endoscopic surgery is practiced worldwide, there
is no consensus on comparative outcomes between transanal endoscopic operation
(TEO) and transanal excision (TAE). In this study, we reviewed our experiences
with these techniques and compared patients who underwent TEO and TAE using
propensity score matching (PSM). METHODS: A total of 207 patients underwent local
rectal tumor excision between January 2008 and November 2015. To overcome
selection bias, we used PSM to achieve a one-to-one TEO: TAE ratio. We included
baseline characteristics, age, sex, surgeon, American Society of
Anesthesiologists score, tumor location (clockwise direction), involved
circumference quadrants, tumor size, and pathology. RESULTS: After PSM, 72
patients were included in each group. The tumor distance from the anal verge was
higher in the TEO group (8.0 [5-10] vs. TAE: 4.0 [3-5], p < 0.001). Complication
rates did not differ between the groups (TEO: 8.3% vs. TAE: 11.1%, p = 0.39). TEO
was associated with a shorter hospital stay (3.01 vs. 4.68 days, p = 0.001),
higher negative margin rate (95.8 vs. 86.1%, p = 0.039), and non-fragmented
specimen rate vs. TAE (98.6 vs. 90.3%, p = 0.029). CONCLUSIONS: TEO was more
beneficial for patients with higher rectal tumors. Regardless of tumor location,
involved circumference quadrants, and tumor size, TEO may more effectively
achieve negative resection margins and non-fragmented specimens. Consequently,
although local excision method according to tumor distance may be important, TEO
will become the standard for rectal tumors.
PMID- 28421263
TI - Bone Mineral Density and Fracture Risk in Ankylosing Spondylitis: A Meta
Analysis.
AB - We conducted a meta-analysis of studies to examine the risk of vertebral and non
vertebral fractures in patients with ankylosing spondylitis (AS). Additionally,
we evaluated the risk factors of vertebral fractures in AS. Two authors
independently searched Embase and Medline for studies that had assessed the risk
of fractures in patients with AS. Twenty-two studies were eligible for the meta
analysis. Patients with AS had high frequency of vertebral fractures [OR (95%
CI): 1.96 (1.52-2.51)]. Major risk factors for vertebral fractures in patients
with AS include low BMD at the femoral neck and total hip, male gender, longer
disease duration, higher BASDAI, higher BASRI, and possibly inflammatory bowel
disease. The risk of non-vertebral fractures [OR (95% CI) 1.10 (1.04-1.15)] was
10% higher in AS patients than in controls. The risk of hip fractures in AS
patients was not statistically significant [OR (95% CI) 1.17 (0.71-1.92)] in our
pooled analysis. We found that patients with AS are at high risk of vertebral
fractures. Male sex, duration of AS, mSASSS, BASRI, and low BMD at the hip and
distal forearm were associated with the risk of vertebral fractures. Current
evidence on the risk of hip fractures in patients with AS is inconsistent. Data
about the effect of NSAIDs and TNF inhibitors on fracture risk in AS are limited.
PMID- 28421266
TI - Reactive oxygen species mediated T lymphocyte abnormalities in an iron-overloaded
mouse model and iron-overloaded patients with myelodysplastic syndromes.
AB - The adverse effects of iron overload have raised more concerns as a growing
number of studies reported its association with immune disorders. This study
aimed to investigate alterations in the immune system by iron overload in
patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model.
The peripheral blood from patients was harvested to test the effect of iron
overload on the subsets of T lymphocytes, and the level of reactive oxygen
species (ROS) was also evaluated. The data showed that iron-overloaded patients
had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant
with higher ROS level in lymphocytes. In order to explore the mechanism, male
C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250
mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and
the blood of each mouse was collected for the analysis of the T lymphocyte
subsets and T cell apoptosis. The results showed that iron overload could reduce
the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase
the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also
found that iron overload induced the apoptosis of T lymphocytes and increased its
ROS level. Furthermore, these effects could be partially recovered after treating
with antioxidant N-acetyl-L-cysteine (NAC) or iron chelator deferasirox (DFX).
Taken together, these observations indicated that iron overload could selectively
affect peripheral T lymphocytes and induce an impaired cellular immunity by
increasing ROS level.
PMID- 28421267
TI - Potential Distribution of Mountain Cloud Forest in Michoacan, Mexico:
Prioritization for Conservation in the Context of Landscape Connectivity.
AB - Landscape connectivity is essential in biodiversity conservation because of its
ability to reduce the effect of habitat fragmentation; furthermore is a key
property in adapting to climate change. Potential distribution models and
landscape connectivity studies have increased with regard to their utility to
prioritizing areas for conservation. The objective of this study was to model the
potential distribution of Mountain cloud forests in the Transversal Volcanic
System, Michoacan and to analyze the role of these areas in maintaining landscape
connectivity. Potential distribution was modeled for the Mountain cloud forests
based on the maximum entropy approach using 95 occurrence points and 17
ecological variables at 30 m spatial resolution. Potential connectivity was then
evaluated by using a probability of connectivity index based on graph theory. The
percentage of variation (dPCk) was used to identify the individual contribution
of each potential area of Mountain cloud forests in overall connectivity. The
different ways in which the potential areas of Mountain cloud forests can
contribute to connectivity were evaluated by using the three fractions derived
from dPCk (dPCintrak, dPCfluxk, and dPCconnectork). We determined that 37,567 ha
of the TVSMich are optimal for the presence of Mountain cloud forests. The
contribution of said area in the maintenance of connectivity was low. The
conservation of Mountain cloud forests is indispensable, however, in providing or
receiving dispersal flows through TVSMich because of its role as a connector
element between another habitat types. The knowledge of the potential capacity of
Mountain cloud forests to promote structural and functional landscape
connectivity is key in the prioritization of conservation areas.
PMID- 28421264
TI - Epidemiology of Sarcopenia: Determinants Throughout the Lifecourse.
AB - Sarcopenia is an age-related syndrome characterised by progressive and
generalised loss of skeletal muscle mass and strength; it is a major contributor
to the risk of physical frailty, functional impairment in older people, poor
health-related quality of life and premature death. Many different definitions
have been used to describe sarcopenia and have resulted in varying estimates of
prevalence of the condition. The most recent attempts of definitions have tried
to integrate information on muscle mass, strength and physical function and
provide a definition that is useful in both research and clinical settings. This
review focuses on the epidemiology of the three distinct physiological components
of sarcopenia, and highlights the similarities and differences between their
patterns of variation with age, gender, geography and time and the individual
risk factors that cluster selectively with muscle mass, strength and physical
function. Methods used to measure muscle mass, strength and physical functioning
and how differences in these approaches can contribute to the varying prevalence
rates will also be described. The evidence for this review was gathered by
undertaking a systematic search of the literature. The descriptive
characteristics of muscle mass, strength and function described in this review
point to the urgent need for a consensual definition of sarcopenia incorporating
these parameters.
PMID- 28421268
TI - Using a Population Model to Inform the Management of River Flows and Invasive
Carp (Cyprinus carpio).
AB - Carp are a highly successful invasive fish species, now widespread, abundant and
considered a pest in south-eastern Australia. To date, most management effort has
been directed at reducing abundances of adult fish, with little consideration of
population growth through reproduction. Environmental water allocations are now
an important option for the rehabilitation of aquatic ecosystems, particularly in
the Murray-Darling Basin. As carp respond to flows, there is concern that
environmental watering may cause floodplain inundation and provide access to
spawning habitats subsequently causing unwanted population increase. This is a
management conundrum that needs to be carefully considered within the context of
contemporary river flow management (natural, environmental, irrigation). This
paper uses a population model to investigate flow-related carp population
dynamics for three case studies in the Murray-Darling Basin: (1) river and
terminal lakes; (2) wetlands and floodplain lakes; and (3) complex river channel
and floodplain system. Results highlight distinctive outcomes depending on site
characteristics. In particular, the terminal lakes maintain a significant source
carp population regardless of river flow; hence any additional within-channel
environmental flows are likely to have little impact on carp populations. In
contrast, large-scale removal of carp from the lakes may be beneficial,
especially in times of extended low river flows. Case studies 2 and 3 show how
wetlands, floodplain lakes and the floodplain itself can now often be inundated
for several months over the carp spawning season by high volume flows provided
for irrigation or water transfers. Such inundations can be a major driver of carp
populations, compared to within channel flows that have relatively little
effecton recruitment. The use of a population model that incorporates river flows
and different habitats for this flow-responsive species, allows for the
comparison of likely population outcomes for differing hydrological scenarios to
improve the management of risks relating to carp reproduction and flows.
PMID- 28421269
TI - Thermal balance of Nellore cattle.
AB - This work aimed at characterizing the thermal balance of Nellore cattle from the
system of indirect calorimetry using a facial mask. The study was conducted at
the Animal Biometeorology Laboratory of the Sao Paulo State University,
Jaboticabal, Brazil. Five male Nellore weighing 750 +/- 62 kg, at similar ages
and body conditions were distributed in four 5 * 5 Latin squares (5 days of
records and five schedules) during 20 days. Physiological and environmental
measurements were obtained from the indirect calorimetry system using a facial
mask. Respiratory parameters, hair coat, skin, and rectal temperature were
continuously recorded. From this, metabolic heat production, sensible and latent
ways of heat transfer were calculated. Metabolic heat production had an average
value of 146.7 +/- 0.49 W m-2 and did not change (P > 0.05) over the range of air
temperature (24 to 35 degrees C). Sensible heat flow reached 60.08 +/- 0.81 W m
2 when air temperature ranged from 24 to 25 degrees C, being negligible in
conditions of temperature above 33 degrees C. Most of the heat produced by
metabolism was dissipated by cutaneous evaporation when air temperature was
greater than 30 degrees C. Respiratory parameters like respiratory rate and
ventilation remained stable (P > 0.05) in the range of temperature studied. Under
shade conditions and air temperature range from 24 to 35 degrees C, metabolic
heat production, respiratory rate, and ventilation of mature Nellore cattle
remain stable, which is indicative of low energetic cost to the thermoregulation.
PMID- 28421270
TI - Climate variability impacts on rainfed cereal yields in west and northwest Iran.
AB - In order to assess the response of wheat and barley to climate variability, the
correlation between variations of yields with local and global climate variables
was investigated in west and northwest Iran over 1982-2013. The global climate
variables were the El Nino-Southern Oscillation (ENSO), Arctic Oscillation (AO),
and North Atlantic Oscillation (NAO) signals. Further, minimum (T min), maximum
(T max), and mean (T mean) temperature, diurnal temperature range (DTR),
precipitation, and reference evapotranspiration (ET0) was used as local weather
factors. Pearson's correlation coefficient was applied to analyze the
relationships between climatic variables and yields. Unlike T min, T mean, ET0,
and T max, the yields were significantly associated with the entire growing
season (EGS) DTR in most sites. Therefore, considering weather extreme variables
such as DTR sheds light on the crop-temperature interactions. It is also found
that the April-May-June (AMJ), October-November-December (OND), and EGS rainfall
variations markedly influence the yields. Unlike the AO and NAO indices, the Nino
4 and SOI (the ENSO-related signals) were significantly correlated with the OND
and EGS precipitation and DTR. Thus, the ENSO anomalies highly impact rainfed
yields through influencing the OND and EGS rainfall and DTR in the studied sites.
As the correlation coefficient of the OND and July-August-September (JAS) Nino-4
with yields was significant (p < 0.05) for almost all locations, the JAS and OND
Nino-4 may be a good proxy for cereal yield forecasting. Further, an
insignificant increment and a significant reduction in yields are expected in La
Nina and El Nino years, respectively, relative to neutral years.
PMID- 28421271
TI - [Hereditary bone tumors].
AB - Hereditary bone tumors are rare and result from mutations affecting cell cycle
regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53,
Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex
signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity
(Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). The majority of
syndromes are incompletely understood and can lead to multiple benign tumors, of
which some might undergo secondary malignant transformation over time
(enchondromatosis: enchondromas, multiple hereditary exostoses: osteochondromas,
Gardner syndrome: osteomas) or bone sarcomas, primarily osteosarcomas as primary
(Li-Fraumeni, Rothmund-Thomson, Werner and Bloom syndromes) or secondary
manifestation (retinoblastoma syndrome) of the disease. Some syndromes
additionally predispose to the development of a variety of other malignant tumors
during life. Compared to sporadically occurring tumors, syndrome-related
neoplasms can differ in the time of manifestation, site and histology, which can
help in recognizing a specific tumor predisposition syndrome.
PMID- 28421272
TI - [The pathology of adverse events with immune checkpoint inhibitors].
AB - BACKGROUND: Immunotherapy has gained importance with the development of new
effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal
antibodies that promote T-cell mediated tumor immune rejection. Checkpoint
blockade also carries the risk of inducing autoimmune reactions ("immune related
adverse events", irAEs). The diagnosis and classification of irAEs constitute a
new and important field in pathology. AIM: Practice-oriented review of the
diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured,
selective literature review based on PubMed und UpToDate (r) online. RESULTS: The
most common irAEs affect the skin, the gastrointestinal tract, the liver, and the
respiratory system. The correct diagnosis and classification of irAEs by an
interdisciplinary care team is essential for appropriate therapy and the
prevention of long-term sequelae. Other important irAEs affect the endocrine
organs, the heart, the joints, the kidneys and the nervous system. Because of
their rarity and/or limited options for bioptic diagnosis, only limited data on
the morphology and pathophysiology of these irAEs are currently available.
Autopsies carried out after ICI therapy constitute an important element of
quality control and allow better documentation of the incidence and pathogenesis
of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and
treatment of irAEs. Future studies may contribute to a better mechanistic
understanding of irAEs for individualized knowledge-based risk assessment.
PMID- 28421273
TI - [Definition, classification, clinical diagnosis and prognosis of fibromyalgia
syndrome : Updated guidelines 2017 and overview of systematic review articles].
AB - BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF
number 145/004, was scheduled for April 2017. METHODS: The guidelines were
developed by 13 scientific societies and 2 patient self-help organizations
coordinated by the German Pain Society. Working groups (n =8) with a total of 42
members were formed balanced with respect to gender, medical expertise, position
in the medical or scientific hierarchy and potential conflicts of interest. A
systematic search of the literature from December 2010 to May 2016 was performed
in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of
evidence were assigned according to the classification system of the Oxford
Centre for Evidence-Based Medicine version 2009. The strength of recommendations
was achieved by multiple step formalized procedures to reach a consensus. The
guidelines were reviewed and approved by the board of directors of the societies
engaged in the development of the guidelines. RESULTS AND CONCLUSION: The
clinical diagnosis of fibromyalgia syndrome can be established by the American
College of Rheumatology (ACR) 1990 classification criteria (with examination of
tender points) or without the examination of tender points by the modified
preliminary diagnostic ACR 2010 or 2011 criteria.
PMID- 28421274
TI - Endometrioid endometrial adenocarcinoma: an increase of G3 cancers?
AB - PURPOSE: Endometrial cancer can be divided into two types: endometrioid Type 1
(G1, G2) has a hormonal driven etiology, while Type 2 is more aggressive (G3
endometrioid, clear cell and serous cancer type) and estrogen independent. We
noticed an increase of more aggressive G3 endometrioid endometrial
adenocarcinomas. This observation is of relevance for daily clinical practice
because therapy depends on the histopathological grading and myometrial invasion.
G3 cancers or myometrial invasion of more than 50% should be hysterectomized
including bilateral adnexectomy with pelvine and paraaortal lymphadenectomy. In
G1/G2 and lower infiltration levels, hysterectomy with adnexectomy without
lymphadenectomy is sufficient. METHODS: Data of the ASF Statistic were used to
analyze the changes in the incidences of patients with endometrioid cancer,
grading groups and their first diagnosed stages between 2006 and 2014. RESULTS:
2611 patients, with 243-341 women per year, were analyzed. The number of
diagnosed G1 tumors increased from 25 to 37% and the G3 tumors from 18 to 32%,
whereas the G2 cancers decreased from 58 to 31%. Despite the rise of G3 tumors,
an increase in age at diagnosis was not observed. The proportions of initial
diagnosed stages (FIGO I-IV) in each grading remained constant over time.
CONCLUSION: Potential consequences in treatment recommendations and prognosis
urge attention to the detected increase of G3 endometrioid cancers.
PMID- 28421275
TI - No association between hand and foot temperature responses during local cold
stress and rewarming.
AB - PURPOSE: The purpose was to examine whether associations exist between
temperature responses in the fingers vs. toes and hand vs. foot during local cold
water immersion and rewarming phases. METHODS: Seventy healthy subjects (58
males, 12 females) immersed their right hand or right foot, respectively, in 8
degrees C water for 30 min (CWI phase), followed by a 15-min spontaneous
rewarming (RW) in 25 degrees C air temperature. RESULTS: Temperature was lower
in the toes than the fingers during the baseline phase (27.8 +/- 3.0 vs. 33.9 +/-
2.5 degrees C, p < 0.001), parts of the CWI phase (min 20-30: 8.8 +/- 0.7 vs.
9.7 +/- 1.4 degrees C, p < 0.001), and during the RW phase (peak temperature:
22.5 +/- 5.1 vs. 32.7 +/- 3.6 degrees C, p < 0.001). Cold-induced vasodilatation
(CIVD) was more common in the fingers than in the toes (p < 0.001). Within the
first 10 min of CWI, 61% of the subjects exhibited a CIVD response in the
fingers, while only 6% of the subjects had a CIVD response in the toes. There was
a large variability of temperature responses both within and between extremities,
and there was a weak correlation between finger- and toe temperature both during
the CWI (r = 0.21, p = 0.08) and the RW phases (r = 0.26, p = 0.03). CONCLUSIONS:
Results suggest that there is generally a lower temperature in the toes than the
fingers after a short time of local cold exposure and that the thermal responses
of the fingers/hands are not readily transferable to the toes/foot.
PMID- 28421276
TI - Erratum to: The laminar organization of the motor cortex in monodactylous
mammals: a comparative assessment based on horse, chimpanzee, and macaque.
PMID- 28421277
TI - Author's reply to a letter-to-the-editor about the paper 'Eardrum thickening
approach for the treatment of patulous Eustachian tube'.
PMID- 28421278
TI - An efficient method to enrich for knock-out and knock-in cellular clones using
the CRISPR/Cas9 system.
AB - Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9
nuclease (CRISPR/Cas9) and Transcription Activator-Like Effector Nucleases
(TALENs) are versatile tools for genome editing. Here we report a method to
increase the frequency of Cas9-targeted cellular clones. Our method is based on a
chimeric construct with a Blasticidin S Resistance gene (bsr) placed out-of-frame
by a surrogate target sequence. End joining of the CRISPR/Cas9-induced double
strand break on the surrogate target can place the bsr in frame, thus providing
temporary resistance to Blasticidin S: this is used to enrich for cells where
Cas9 is active. By this approach, in a real experimental setting, we disrupted
the Aicda gene in ~70% of clones from CH12F3 lymphoma cells (>40% biallelically).
With the same approach we knocked in a single nucleotide to reconstruct the frame
of Aicda in these null cells, restoring the function in ~37% of the clones (less
than 10% by the standard approach). Targeting of single nucleotide changes in
other genes yielded analogous results. These results support our enrichment
method as an efficient tool in genome editing.
PMID- 28421280
TI - Systems biology of seeds: deciphering the molecular mechanisms of seed storage,
dormancy and onset of germination.
AB - Seeds are heterogeneous storage reserves with wide array of storage compounds
that include various soluble carbohydrates, starch polymer, storage proteins and
lipids. These stored reserves comprise 70% of the world's caloric intake in the
form of food and animal feed produced through sustainable agriculture, which
contributes to food and nutritional security. Seed systems biology remains an
enigmatic subject in understanding seed storage processes, maturation and pre
germinative metabolism. The reviews and research articles covered in this special
issue of Plant Cell Reports highlight recent advances made in the area of seed
biology that cover various systems biology applications such as gene regulatory
networks, metabolomics, epigenetics and the role of micro-RNA in seed
development.
PMID- 28421279
TI - Sporulation: how to survive on planet Earth (and beyond).
AB - Sporulation is a strategy widely utilized by a wide variety of organisms to adapt
to changes in their individual environmental niches and survive in time and/or
space until they encounter conditions acceptable for vegetative growth. The
spores produced by bacteria have been the subjects of extensive studies, and
several systems such as Bacillus subtilis have provided ample opportunities to
understand the molecular basis of spore biogenesis and germination. In contrast,
the spores of other microbes, such as fungi, are relatively poorly understood.
Studies of sporulation in model systems such as Saccharomyces cerevisiae and
Aspergillus nidulans have established a basis for investigating eukaryotic
spores, but very little is known at the molecular level about how spores
function. This is especially true among the spores of human fungal pathogens such
as the most common cause of fatal fungal disease, Cryptococcus neoformans. Recent
proteomic studies are helping to determine the molecular mechanisms by which
pathogenic fungal spores are formed, persist and germinate into actively growing
agents of human disease.
PMID- 28421281
TI - Hearing diversity in moths confronting a neotropical bat assemblage.
AB - The tympanal ear is an evolutionary acquisition which helps moths survive
predation from bats. The greater diversity of bats and echolocation strategies in
the Neotropics compared with temperate zones would be expected to impose
different sensory requirements on the neotropical moths. However, even given some
variability among moth assemblages, the frequencies of best hearing of moths from
different climate zones studied to date have been roughly the same: between 20
and 60 kHz. We have analyzed the auditory characteristics of tympanate moths from
Cuba, a neotropical island with high levels of bat diversity and a high incidence
of echolocation frequencies above those commonly at the upper limit of moths'
hearing sensitivity. Moths of the superfamilies Noctuoidea, Geometroidea and
Pyraloidea were examined. Audiograms were determined by non-invasively measuring
distortion-product otoacoustic emissions. We also quantified the frequency
spectrum of the echolocation sounds to which this moth community is exposed. The
hearing ranges of moths in our study showed best frequencies between 36 and 94
kHz. High sensitivity to frequencies above 50 kHz suggests that the auditory
sensitivity of moths is suited to the sounds used by sympatric echolocating bat
fauna. Biodiversity characterizes predators and prey in the Neotropics, but the
bat-moth acoustic interaction keeps spectrally matched.
PMID- 28421283
TI - Shunting of the over 80s in normal pressure hydrocephalus.
AB - BACKGROUND: Idiopathic normal pressure hydrocephalus is predominantly a disease
of the elderly. By its nature, many of those who present to clinic are in
advanced old age with multiple comorbidities. Majority of patients treated are
younger than 80 years old. We present the clinical outcomes and complication
rates of patients over the age of 80 years at the time of operation, during the
past 11 years at a single institution. METHODS: Retrospective analysis of
clinical records of all patients over the age of 80 years, who presented to our
institution between 2006 and 2016. Results were analysed for co-morbidities,
immediate and delayed complications, change in mobility/cognitive function post
shunting of hydrocephalus. RESULTS: 39 patients (24 male, 15 female) met
criteria. Mean [SD] age at the time of shunt insertion was 84 years (+/- 3.22)
(range 80-94). No patients developed immediate CSF infection or sub-dural
collection, or extended length of stay due to surgical or anaesthetic
complications. There were no peri-operative or anaesthetic complications. 4
patients required a delayed surgical revision to encourage greater CSF drainage.
3 patients went on to develop delayed subdural haematoma, 1 of which was
associated with trauma, 2 through overdrainage. 1 patient experienced poor post
operative wound healing and subsequently underwent removal of shunt. Of the 34
patient followed up, 27 patients (79.4%) improved in their mobility. (64.7%)
patients/families reported symptomatic improvement in their cognition and memory.
6 (17.7%) patients did not experience an improvement in either mobility or
cognitive function. CONCLUSIONS: Our data supports the assertion that, with
proper patient selection, shunting of the over 80s with iNPH is a safe and
effective procedure.
PMID- 28421282
TI - Associations between a Mediterranean diet pattern and inflammatory biomarkers in
European adolescents.
AB - AIM: To test whether the Mediterranean diet score and each food-subgroup is
associated with inflammatory biomarkers in European adolescents. METHODS: In 464
adolescents (13-17 years) of the European HELENA study, data were available on
body composition, inflammation markers, and food intake determined by two
computerized 24-h recalls. The Mediterranean diet score and its food-subgroups
(Vegetables, Fruits and Nuts, Pulses, Cereal and Roots, Monounsaturated/Saturated
fat ratio, Dairy, Fish, Meat and Alcohol) were evaluated. A set of inflammation
related biomarkers was measured: IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, TGFbeta-1,
TNF-alpha, sVCAM-1, sICAM1, sE-selectin, white blood cells, lymphocytes, CD3,
CRP, GGT, ALT, and homocysteine. Multivariate and multiple linear regression
analyses were adjusted for age, sex, country, socioeconomic status, paternal and
maternal education, adiposity, and smoking habits. RESULTS: The Mediterranean
diet score was positively associated with CRP, and negatively with sVCAM-1. The
subgroups showed the following positive/negative associations: Vegetables with IL
10(+), CRP(+), CD3(+), ALT(+), lymphocytes(+), sE-selectin(-); Fruits and Nuts
with IL-4(-), TNF-alpha; Pulses with IL-5(+), IL-6(+), IL-2(-); Cereals and Roots
with IL-6(-), IL-10(-); Monounsaturated/Saturated-fat ratio with IL-6(+), TGFbeta
1(+), sVCAM-1(+boys, -girls), homocysteine(-); Dairy with IL-1(+), IL-5(+), IL
6(+), IL-10(+), TGFbeta-1(+), homocysteine(-); Fish with homocysteine(-); Meat
with IL-2(+), IL-10(+); Alcohol with CRP(+), lymphocytes(-). Sex differences were
found. CONCLUSION: Some specific food-inflammation associations were found,
suggesting that diet is to a certain extent already related to inflammation in
adolescents and can be used in disease prevention. Also some counterintuitive
results were found, which might be due to grouping very different foods into a
single group, besides considering that the human body may respond differently
depending on the interaction between diet, lifestyle, genetics, biochemical
individuality, age and sex.
PMID- 28421284
TI - Oropharyngeal dysphagia in secondary normal pressure hydrocephalus due to
corticobulbar tract compression: cases series and review of literature.
AB - The association and mechanism involved in swallowing disturbance and normal
pressure hydrocephalus (NPH) needs to be established. We report a case report
where a patient who showed progressive swallowing dysfunction was diagnosed with
secondary NPH. Tractography analysis showed corticobulbar tract compression by
ventricular dilation. Drainage operation led to the recovery of tract volume with
an improvement of swallowing function. We also report ten case series in which
secondary NPH was associated with a swallowing disturbance. In these cases,
dysphagia also showed improvement after shunt operation. We review the literature
regarding the corticobulbar tract and its association with swallowing disturbance
and the possible underlying pathophysiological mechanism in secondary NPH. This
report highlights that swallowing disturbance may manifest in those with
secondary NPH due to corticobulbar tract involvement. Our findings suggest that
involvement of the corticobulbar tract may be a possible cause of dysphagia in
secondary NPH that may be reversible after shunt operation.
PMID- 28421285
TI - [Erratum to: Guidelines from the DOG, RG and BVA: retinal artery occlusion :
November 2016 status].
PMID- 28421286
TI - [Listening to music in old age : Investigation of utilization and psychosocial
resources].
AB - BACKGROUND: Studies with younger participants have shown that listening to music
is used to achieve a multitude of positive effects that can be summarized by
three fundamental dimensions: self-awareness, social relatedness and regulation
of mood and arousal. For the elderly, these effects contain a high potential with
respect to alleviation of affective symptoms and enhancement of social
participation; however, it is still unclear if the elderly exhibit the same
pattern of fundamental uses of listening to music as younger persons and how they
evaluate their access to music in different housing situations. MATERIAL AND
METHODS: To answer these questions, 115 persons (aged 57-94 years) in different
housing situations were asked for their motives for listening to music and their
satisfaction with various aspects of access to music. RESULTS: The elderly showed
the same pattern of the three fundamental dimensions of the use of listening to
music as younger respondents, although specific uses were more pronounced, such
as relaxation, reminiscing, and compensation for loneliness; however, the general
intensity of the use of listening to music was lower. Older people saw deficits
in the frequency, coordination, and communication of musical arrangements in
their residential environment. CONCLUSION: Older people listen to music to obtain
specific effects in the same way as younger people do; however, the decreasing
intensity of the use of listening to music, together with the desires of the
older respondents, demonstrate a need for more musical arrangements that should
be better coordinated, communicated, and preferably personalized.
PMID- 28421288
TI - [83th Annual Meeting of the German Cardiac Society - Cardiac and Circulation
Research, April 19.- 22. 2017, Mannheim].
PMID- 28421287
TI - [Age 89 years, depression, fall with pelvic fracture, severe confusion -
serotonin syndrome : Differential diagnosis, importance of CYP450 and economic
considerations].
AB - A case study of an 89-year-old patient is reported, who was admitted to hospital
because of immobility due to pain. After the cause of the pain could initially be
clarified and treated, the further clinical course in this very old woman showed
an alarming symptom complex of agitation, confusion and cognitive deterioration,
which took on grave forms. The work-up of this case showed a typical
constellation of pain and depression in old age; however, the pharmaceutical
treatment in this case is not atypical and could lead to a severe serotonin
syndrome. The interaction, diagnostics, differential diagnosis, pharmacological,
functional, codification and economic aspects of the course of the disease are
discussed.
PMID- 28421290
TI - Pulsatile high-dose treatment with antiangiogenic tyrosine kinase inhibitors
improves clinical antitumor activity.
PMID- 28421289
TI - Adult male northern elephant seals maintain high rates of glucose production
during extended breeding fasts.
AB - Many species undergo natural fasts as part of their life histories. Extended
fasting is associated with increased beta-oxidation of fatty acids and reduced
oxidation of glucose to minimize commitment of body protein to gluconeogenesis.
However, the metabolic strategies used to sustain extended fasts simultaneous
with high rates of energy expenditure are not well understood. Studies in fasting
adult female and weanling northern elephant seals (NES) have revealed high rates
of endogenous glucose production (EGP) under constraints of high nutrient demand
for lactation or development but relatively low rates of metabolism. These
studies revealed low rates of glucose oxidation and high rates of glucose
recycling through the Cori cycle. We measured rates of glucose flux in fasting
adult male NES to assess how significantly longer fasting durations, higher
metabolic rates, and greater rates of muscular activity affect glucose kinetics.
We measured glucose turnover in 18 adult males using the clearance of [6-H3]
glucose during breeding and molting. Adult male NES maintain high rates of EGP
across extended fasts. EGP greatly exceeded estimated needs for glucose-dependent
tissues, varied directly with plasma insulin and lactate concentrations, and was
inversely related to plasma ketoacid concentrations. Together, these findings
suggest that high rates of glucose production and recycling during breeding
maintain high blood glucose levels to support glucose-dependent tissues while
minimizing production of ketoacids and commitment of protein stores to glucose
production.
PMID- 28421291
TI - Tick-borne viral encephalomyeloradiculitis complicated by severe autonomic
myenteric involvement resulting in irreversible adynamic ileus.
PMID- 28421292
TI - Phylogenetic Insight into Zika and Emerging Viruses for a Perspective on
Potential Hosts.
AB - Global viral diversity is substantial, but viruses that contribute little to the
public health burden or to agricultural damage receive minimal attention until a
seemingly unimportant virus becomes a threat. The Zika virus (ZIKV) illustrated
this, as there was limited information and awareness of the virus when it was
identified as a public health emergency in February 2016. Predicting which virus
may pose a future threat is difficult. This is in part because significant
knowledge gaps in the basic biology and ecology of an emerging virus can impede
policy development, delay decision making, and hinder public health action. We
suggest using a phylogenetic framework of pathogens and their infected host
species for insight into which animals may serve as reservoirs. For example,
examining flaviviruses closely related to ZIKV, the phylogenetic framework
indicates New World monkeys are the most likely candidates to be potential
reservoirs for ZIKV. Secondarily, mammals that are in close proximity to humans
should be considered because of the increased opportunity for pathogen exchange.
The increase in human-mediated environmental change is accelerating the
probability of another previously overlooked virus becoming a significant
concern. By investing in basic science research and organizing our knowledge into
an evolutionary framework, we will be better prepared to respond to the next
emerging infectious disease.
PMID- 28421293
TI - Failure and revision rates of proximal humeral fracture treatment with the use of
a standardized treatment algorithm at a level-1 trauma center.
AB - BACKGROUND: The aims of this study were to evaluate treatment failure and
revision rates of proximal humeral fracture (PHF) treatment with a standardized
treatment algorithm within the reality of a level-1 trauma center and to identify
predictors of subsequent surgery. MATERIALS AND METHODS: The medical database of
a level-1 trauma center was screened for all primary treatments of PHFs between
January 2009 and June 2012. Medical records and imaging were analyzed to identify
the fracture morphology, pre-existing diseases, revision surgeries and treatment
failures (conversion to another treatment). The patients were asked about
subsequent surgeries by phone. A functional outcome questionnaire was mailed to
participating patients. RESULTS: Follow-up data were available for 423 of 521
patients (312 females, 111 males). The mean age at the time of primary treatment
was 68.3 years; mean follow-up was 24.6 +/- 12.3 months. The overall rate of
mandatory re-operations was 15.6%, including a failure rate of 8.3%; another 7.6%
of patients had additional arthroscopic surgeries. Treatment with anatomic hemi
prostheses was associated with the highest re-operation rates, and lowest
outcomes. Involvement of the medial calcar region, complex fracture morphologies,
cigarette smoking and alcohol-abuse were predictors for subsequent surgery.
Patients without subsequent surgery had significantly higher functional outcome
scores than patients with additional surgery. CONCLUSIONS: With the use of a
standardized treatment algorithm no treatment modality was at significantly
higher risk for having additional surgery. Complex fracture types, involvement of
the medial calcar, cigarette-smoking and alcohol-abuse were associated with
subsequent surgeries. LEVEL OF EVIDENCE: Level IV case series.
PMID- 28421294
TI - A prospective comparison of intra-arterial chemotherapy combined with
intravesical chemotherapy and intravesical chemotherapy alone after transurethral
resection with a thulium laser in high-risk non-muscle invasive bladder cancer.
AB - : Objective To compare intra-arterial chemotherapy combined with intravesical
chemotherapy with intravesical chemotherapy alone in the treatment of high-risk
non-muscle invasive bladder cancer (HRBC) after thulium laser resection of a
bladder tumor (TmLRBT). MATERIALS AND METHODS: From January 2009 to December
2013, 283 patients with HRBC were randomly assigned to the combined group (group
A, n = 141) or intravesical chemotherapy-alone group (group B, n = 142) after
TmLRBT. Intra-arterial chemotherapy was administered after initial TmLRBT, with 3
courses at 4-week intervals. Each course consisted of cisplatin (50 mg/m2) and
epirubicin (30 mg/m2). Intravesical chemotherapy was administered in both groups,
including an immediate 50 mg of epirubicin instillation after TmLRBT and weekly
maintenance for 8 weeks, followed by monthly maintenance for 1 year. RESULTS: The
recurrence rate was 29.1% (41/141) in group A and 42.9% (61/142) in group B, with
a significant difference (p = 0.01). The progression rate was 15.6% (22/141) in
group A and 25.3% (36/142) in group B, with a significant difference (p = 0.039).
Patients with concomitant carcinoma in situ (CIS) also had a lower recurrence
rate and progression rate in group A compared to those in group B (p = 0.006 and
p = 0.03, respectively). On univariate and multivariate logistic regression
analyses, patients with low-grade histology had a higher reccurrence-free rate.
Multivariate COX analysis of tumor-related factors suggested that concomitant CIS
was the only significant prognostic factor associated with poorer recurrence-free
survival and progression-free survival. CONCLUSIONS: Intra-arterial chemotherapy
combined with intravesical chemotherapy could reduce the risk of recurrence and
progression compared to intravesical chemotherapy alone in HRBC.
PMID- 28421295
TI - Do Modic changes affect cervical sagittal alignment and motion in symptomatic
patients?
AB - PURPOSE: The cervical segmental instability often occurs simultaneously with
Modic changes (MCs). However, it is unknown whether there is a relation between
the two diseases. The aim of this study was to evaluate the relationship between
MCs and cervical segmental instability, cervical curvature and range of motion
(ROM) in the cervical spine. METHODS: A total of 464 patients with neck pain or
cervical neurologic symptoms who underwent imaging examination were analyzed
retrospectively. Based on MRI imaging cervical MCs were diagnosed, and patients
were divided into with or without MCs groups. The cervical curvature and range of
motion were measured. We compared the incidence of cervical instability, cervical
curvature and ROM between the two group patients and their relationships with MCs
were studied. Logistic regression was used to study the risk factors associated
with MCs. RESULTS: MCs were observed in 94 of 464 patients and 122 of total 2320
cervical segments and were most frequent at C5-6 segment. The incidence of the
cervical instability was significantly higher in patients with MCs than those
without MCs at cervical level C3-7. In addition, cervical curvature and ROM in
patients with MCs were less than those without MCs. Logistic regression analysis
showed that the occurrence of cervical spine instability, less cervical curvature
and ROM were risk factors for MCs. CONCLUSIONS: Patients with MCs were prone to
have cervical instability at the same cervical level and may have a higher
possibility of less cervical curvature and ROM.
PMID- 28421296
TI - Metabolite signatures of doxorubicin induced toxicity in human induced
pluripotent stem cell-derived cardiomyocytes.
AB - Drug-induced off-target cardiotoxicity, particularly following anti-cancer
therapy, is a major concern in new drug discovery and development. To ensure
patient safety and efficient pharmaceutical drug development, there is an urgent
need to develop more predictive cell model systems and distinct toxicity
signatures. In this study, we applied our previously proposed repeated exposure
toxicity methodology and performed 1H NMR spectroscopy-based extracellular
metabolic profiling in culture medium of human induced pluripotent stem cell
derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer
agent. Single exposure to DOX did not show alteration in the basal level of
extracellular metabolites while repeated exposure to DOX caused reduction in the
utilization of pyruvate and acetate, and accumulation of formate compared to
control culture medium. During drug washout, only pyruvate showed reversible
effect and restored its utilization by hiPSC-CMs. On the other hand, formate and
acetate showed irreversible effect in response to DOX exposure. DOX repeated
exposure increased release of lactate dehydrogenase (LDH) in culture medium
suggesting cytotoxicity events, while declined ATP levels in hiPSC-CMs. Our data
suggests DOX perturbed mitochondrial metabolism in hiPSC-CMs. Pyruvate, acetate
and formate can be used as metabolite signatures of DOX induced cardiotoxicity.
Moreover, the hiPSC-CMs model system coupled with metabolomics technology offers
a novel and powerful approach to strengthen cardiac safety assessment during new
drug discovery and development.
PMID- 28421297
TI - Suppression of Th1 differentiation by tryptophan supplementation in vivo.
AB - Metabolism of the essential amino acid tryptophan (trp) is a key endogenous
immunosuppressive pathway restricting inflammatory responses. Tryptophan
metabolites promote regulatory T cell (Treg) differentiation and suppress
proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that
treatment with natural and synthetic tryptophan metabolites can suppress
autoimmune neuroinflammation in preclinical animal models. Here, we tested if
oral intake of tryptophan would increase immunosuppressive tryptophan metabolites
and ameliorate autoimmune neuroinflammation as a safe approach to treat
autoimmune disorders like multiple sclerosis (MS). Without oral supplementation,
systemic kynurenine levels decrease during the initiation phase of experimental
autoimmune encephalomyelitis (EAE), a mouse model of MS, indicating systemic
activation of tryptophan metabolism. Daily oral gavage of up to 10 mg/mouse/day
was safe and increased serum kynurenine levels by more than 20-fold for more than
3 h after the gavage. While this treatment resulted in suppression of myelin
specific Th1 responses, there was no relevant impact on clinical disease
activity. These data show that oral trp supplementation at subtoxic
concentrations suppresses antigen-specific Th1 responses, but suggest that the
increase in trp metabolites is not sustained enough to impact neuroinflammation.
PMID- 28421298
TI - Dog rivalry impacts following behavior in a decision-making task involving food.
AB - Dogs learn a great deal from humans and other dogs. Previous studies of socially
influenced learning between dogs have typically used a highly trained
demonstrator dog who is unfamiliar to the observer. Because of this, it is
unknown how dynamics between familiar dogs may influence their likelihood of
learning from each other. In this study, we tested dogs living together in two
dog households on whether individual dogs' rivalry scores were associated with
performance on a local enhancement task. Specifically, we wanted to know whether
dog rivalry impacted whether an observer dog would approach a plate from which a
demonstrator dog had eaten all available food, or whether the observer dog would
approach the adjacent plate that still contained food. Dog rivalry scores were
calculated using the Canine Behavioral Assessment and Research Questionnaire and
indicated each dog's tendency to engage aggressively with the other household
dog. Low-rivalry dogs were more likely to approach the empty plate than high
rivalry dogs when the observer dog was allowed to approach the plates immediately
after the demonstrator had moved out of sight. This difference between low- and
high-rivalry dogs disappeared, however, when observer dogs had to wait 5 s before
approaching the plates. The same pattern was observed during a control condition
when a human removed the food from a plate. Compared to low-rivalry dogs, high
rivalry dogs may pay less attention to other dogs due to a low tolerance for
having other dogs in close proximity.
PMID- 28421299
TI - Compared effects of calcium and sodium polystyrene sulfonate on mineral and bone
metabolism and volume overload in pre-dialysis patients with hyperkalemia.
AB - BACKGROUND: Hyperkalemia is prevalent in end-stage renal disease patients, being
involved in life-threatening arrhythmias. Although polystyrene sulfonate (PS) is
commonly used for the treatment of hyperkalemia, direct comparison of effects
between calcium and sodium PS (CPS and SPS) on mineral and bone metabolism has
not yet been studied. METHODS: In a randomized and crossover design, 20 pre
dialysis patients with hyperkalemia (>5 mmol/l) received either oral CPS or SPS
therapy for 4 weeks. RESULTS: After 4-week treatments, there was no significant
difference of changes in serum potassium (K) from the baseline (DeltaK) between
the two groups. However, SPS significantly decreased serum calcium (Ca) and
magnesium (Mg) and increased intact parathyroid hormone (iPTH) values, whereas
CPS reduced iPTH. DeltaiPTH was inversely correlated with DeltaCa and DeltaMg (r
= -0.53 and r = -0.50, respectively). Furthermore, sodium (Na) and atrial
natriuretic peptide (ANP) levels were significantly elevated in patients with
SPS, but not with CPS, whereas DeltaNa and DeltaANP were significantly correlated
with each other in all the patients. We also found that DeltaNa and Delta(Na to
chloride ratio) were positively correlated with DeltaHCO3-. In artificial colon
fluid, CPS increased Ca and decreased Na. Furthermore, SPS greatly reduced K, Mg,
and NH3. CONCLUSION: Compared with SPS, CPS may be safer for the treatment of
hyperkalemia in pre-dialysis patients, because it did not induce
hyperparathyroidism or volume overload.
PMID- 28421300
TI - Functional Teas from the Leaves of Arbutus unedo: Phenolic Content, Antioxidant
Activity, and Detection of Efficient Radical Scavengers.
AB - The phenolic content/composition and antioxidant activity of hot/cold infusion
and decoction from the leaves of Arbutus unedo were studied for the first time.
1,1-diphenyl-2-picrylhydrazyl (DPPH?), 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) radical cation (ABTS?+), crocin-bleaching, copper-reducing, and
liposome accelerated oxidation assays were used for the evaluation of the
activity in vitro. In vivo, the extracts were examined for their ability to
protect S. cerevisiae cells from H2O2 induced oxidative stress. An on-line high
performance liquid chromatography-DPPH? assay was applied to identify potent
radical scavengers and comment on their contribution to the total activity. The
addition of leaves to boiling water (decoction) was the most appropriate practice
to apply since the highest phenol intake (220.2 mg gallic acid/cup served) was
obtained. Additionally, its antioxidant activity was equal or superior to that of
the other extracts. Flavonols (~51-61 mg/g dry extract) were the main phenols in
all the extracts, with quercitrin accounting for ~20% of the total phenol amount.
The on-line DPPH? method verified the high potency of the decoction and indicated
as the most active radical scavengers, two galloylquinic acid derivatives and
myricitrin, accounting for ~28-45% and ~11-13% of the total scavenging,
respectively. Present data may contribute to the future exploitation of A. unedo
leaves by the food industry for health-promoting herbal tea preparations and
dietary supplements.
PMID- 28421301
TI - Multiple sclerosis and amyotrophic lateral sclerosis: a human leukocyte antigen
challenge.
AB - Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are two different
central nervous system pathology that, according to the most accredited
hypotheses, recognize a different etiopathogenesis. The simultaneous occurrence
of MS and ALS is quite unusual. To our knowledge, only three cases have been so
far described by clinical, laboratory, and post-mortem studies. We report four
new cases of this peculiar combination that have been observed and are herein
described, included their human leukocyte antigen (HLA) profile studies. On the
basis that three out of four patients in our case series presented HLA-B*18:01A,
we may hypothesize that this antigen could play a role in developing both
diseases.
PMID- 28421302
TI - Clinical and MRI improvement in a case of progressive multifocal
leukoencephalopathy.
PMID- 28421303
TI - Erratum to: Geo-helminthiasis among migrants in Sicily: A possible focus for re
emerging neurocysticercosis in Europe.
PMID- 28421304
TI - Increased autophagic degradation contributes to the neuroprotection of hydrogen
sulfide against cerebral ischemia/reperfusion injury.
AB - Hydrogen sulfide (H2S), an endogenous gaseous signal molecule, exhibits
protective effect against ischemic injury. However, its underlying mechanism is
not fully understood. We have recently reported that exogenous H2S decreases the
accumulation of autophagic vacuoles in mouse brain with ischemia/reperfusion
(I/R) injury. To further investigate whether this H2S-induced reduction of
autophagic vacuoles is caused by the decreased autophagosome synthesis and/or the
increased autophagic degradation inautophagic flux, we performed in vitro and in
vivo studies using SH-SY5Y cells for the oxygen and glucose
deprivation/reoxygenation (OGD/R) and mice for the cerebral I/R, respectively.
NaHS (a donor of H2S) treatment significantly increased cell viability and
reduced cerebral infarct volume. NaHS treatment reduced the OGD/R-induced
elevation in LC3-II (an autophagic marker), which was completely reversed by co
treatment with an autophagic flux inhibitor bafilomycin A1 (BafA1). However, H2S
did not affect the OGD/R-induced increase of the ULK1 self-association and
decrease of the ATG13 phosphorylation, which are the critical steps for the
initiation of autophagosome formation. Cerebral I/R injury caused an increase in
LC3-II, a decrease in p62 and the accumulation of autophagosomes in the cortex
and the hippocampus, which were inhibited by NaHS treatment. This H2S-induced
decline of LC3-II in ischemic brain was reversed by BafA1. Moreover, BafA1
treatment abolished the protection of H2S on the cerebral infarction.
Collectively, the neuroprotection of exogenous H2S against ischemia/hypoxia and
reperfusion/reoxygenation injury is mediated by the enhancement of autophagic
degradation.
PMID- 28421305
TI - The utility of global longitudinal strain in the identification of prior
myocardial infarction in patients with preserved left ventricular ejection
fraction.
AB - Prior myocardial infarction (MI) is associated with increased mortality and is
prevalent in certain high risk patient groups. Electrocardiogram may be used in
diagnosis, however, sensitivity is limited, thus non-invasive imaging techniques
may improve diagnosis. We investigated whether global longitudinal strain (GLS)
and longitudinal strain parameters are reduced in patients with prior MI but
preserved left ventricular ejection fraction (LVEF). The study included 40
clinical patients with prior MI occurring >3 months previously (defined as
subendocardial hyperenhancement on late Gadolinium enhancement imaging) with LVEF
>= 55% and 40 controls matched for age and LVEF. GLS, global longitudinal strain
rate (GLSR) and early diastolic longitudinal strain rate (GLSRe) were measured
from cine imaging feature tracking analysis. Presence of wall motion abnormality
(WMA) and minimum systolic wall thickening (SWT) were calculated from cine
imaging. GLS was -17.3 +/- 3.7% in prior MI versus -19.3 +/- 1.9% in controls (p
= 0.012). GLSR was -88.0 +/- 33.7%/s in prior MI versus -103.3 +/- 26.5%/s in
controls (p = 0.005). GLSRe was 76.4 +/- 28.4%/s in prior MI versus 95.5 +/-
26.0%/s in controls (p = 0.001). GLS accurately identified prior MI [AUC 0.662
(95% CI 0.54-0.785) p = 0.012] whereas WMA [AUC 0.500 (95% CI 0.386-0.614) p =
1.0] and minimum SWT [AUC 0.609 (95% CI 0.483-0.735) p = 0.093] did not. GLS,
GLSR and GLSRe are reduced in prior MI with preserved LVEF. Normal LVEF and lack
of WMA cannot exclude prior MI. Prior MI should be considered when reduced GLS,
GLSR or GLSRe are detected by non-invasive imaging.
PMID- 28421306
TI - Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Regulate the
Disposition of Acacetin Glucuronides.
AB - PURPOSE: To determine the mechanism responsible for acacetin glucuronide
transport and the bioavailability of acacetin. METHODS: Area under the curve
(AUC), clearance (CL), half-life (T1/2) and other pharmacokinetic parameters were
determined by the pharmacokinetic model. The excretion of acacetin glucuronides
was evaluated by the mouse intestinal perfusion model and the Caco-2 cell model.
RESULTS: In pharmacokinetic studies, the bioavailability of acacetin in FVB mice
was 1.3%. Acacetin was mostly exposed as acacetin glucuronides in plasma. AUC of
acacetin-7-glucuronide (Aca-7-Glu) was 2-fold and 6-fold higher in Bcrp1 (-/-)
mice and Mrp2 (-/-) mice, respectively. AUC of acacetin-5-glucuronide (Aca-5-Glu)
was 2-fold higher in Bcrp1 (-/-) mice. In mouse intestinal perfusion, the
excretion of Aca-7-Glu was decreased by 1-fold and 2-fold in Bcrp1 (-/-) and Mrp2
(-/-) mice, respectively. In Caco-2 cells, the efflux rates of Aca-7-Glu and Aca
5-Glu were significantly decreased by breast cancer resistance protein (BCRP)
inhibitor Ko143 and multidrug resistance protein 2 (MRP2) inhibitor LTC4. The use
of these inhibitors markedly increased the intracellular acacetin glucuronide
content. CONCLUSIONS: BCRP and MRP2 regulated the in vivo disposition of acacetin
glucuronides. The coupling of glucuronidation and efflux transport was probably
the primary reason for the low bioavailability of acacetin.
PMID- 28421307
TI - An Efficient and Rapid Method to Monitor the Oxidative Degradation of Protein
Pharmaceuticals: Probing Tyrosine Oxidation with Fluorogenic Derivatization.
AB - PURPOSE: The loss of potency of protein therapeutics can be linked to the
oxidation of specific amino acid residues leading to a great variety of oxidative
modifications. The comprehensive identification of these oxidative modifications
requires high-resolution mass spectrometry analysis, which requires time and
expensive resources. Here, we propose a fluorogenic derivatization method of
oxidized Tyr and Phe yielding benzoxazole derivatives, as an orthogonal technique
for the rapid screening of protein oxidation. METHODS: Four model proteins, IgG1,
human growth hormone (hGH), insulin and bovine serum albumin (BSA) were exposed
to oxidation via peroxyl radicals and metal-catalyzed reactions and efficiently
screened by fluorogenic derivatization of Tyr and Phe oxidation products.
Complementary LC-MS analysis was done to identify the extent of methionine
oxidation in oxidized proteins. RESULTS: The Fluorogenic derivatization technique
can easily be adapted to a 96-well plate, in which several protein formulations
can be screened in short time. Representatively for hGH, we show that the
formation of benzoxazole parallels the oxidation of Met to methionine sulfoxide
which enables estimation of Met oxidation by just recording the fluorescence.
CONCLUSIONS: Our rapid fluorescence based screening allows for the fast
comparison of the stability of multiple formulations.
PMID- 28421308
TI - An Intelligent Remote Monitoring System for Total Knee Arthroplasty Patients.
AB - For the first six weeks following total knee arthroplasty (TKA), a patient will
attend an outpatient clinic typically seen twice weekly. Here, an exercise regime
is performed and improvement assessed using a hand held goniometer that measures
the maximum angle of knee flexion, an important metric of progress. Additionally
a series of daily exercises is performed at home, recorded in a diary. This
protocol has problems. Patients must attend the hospital with assistance since
they are not permitted to drive for six weeks following the procedure;
appointments are sometimes missed; there are occasionally not enough
physiotherapy appointment available; furthermore, it is difficult to be sure that
patients are compliant with their exercises at home. The economic and social
costs are therefore significant both to the patient and the health service. We
describe here an automatic system that performs the monitoring of knee flexion
within a domestic environment rather than in a hospital setting. It comprises a
master and slave sensor unit that attach using Velcro straps to the thigh and
shin above and below the operation wound. The patient performs the prescribed
knee exercises whilst wearing the device, during which time it measures and
records the angles of knee flexion. The device utilises the Global System for
Mobile Communications (GSM) infrastructure to transmit data through the Internet
to a secure hospital-based server using an on-board GSM modem. The clinician is
then able to view and interpret the information from any computer with internet
access and the software. The system does not require the patient to possess a
mobile telephone, a computer, or have internet access; the necessary
communications technology is completely integrated into the device.
PMID- 28421309
TI - Genetic makeup of Shiga toxin-producing Escherichia coli in relation to clinical
symptoms and duration of shedding: a microarray analysis of isolates from Swedish
children.
AB - Shiga toxin (Stx)-producing Escherichia coli (STECs) cause non-bloody diarrhea,
hemorrhagic colitis, and hemolytic uremic syndrome, and are the primary cause of
acute renal failure in children worldwide. This study investigated the
correlation of genetic makeup of STEC strains as revealed by DNA microarray to
clinical symptoms and the duration of STEC shedding. All STEC isolated (n = 96)
from patients <10 years of age in Jonkoping County, Sweden from 2003 to 2015 were
included. Isolates were characterized by DNA microarray, including almost 280
genes. Clinical data were collected through a questionnaire and by reviewing
medical records. Of the 96 virulence genes (including stx) in the microarray, 62
genes were present in at least one isolate. Statistically significant differences
in prevalence were observed for 21 genes when comparing patients with bloody
diarrhea (BD) and with non-bloody stool (18 of 21 associated with BD). Most genes
encode toxins (e.g., stx2 alleles, astA, toxB), adhesion factors (i.e. espB_O157,
tir, eae), or secretion factors (e.g., espA, espF, espJ, etpD, nleA, nleB, nleC,
tccP). Seven genes were associated with prolonged stx shedding; the presence of
three genes (lpfA, senB, and stx1) and the absence of four genes (espB_O157,
espF, astA, and intI1). We found STEC genes that might predict severe disease
outcome already at diagnosis. This can be used to develop diagnostic tools for
risk assessment of disease outcome. Furthermore, genes associated with the
duration of stx shedding were detected, enabling a possible better prediction of
length of STEC carriage after infection.
PMID- 28421310
TI - Comparison of Selected Protein Levels in Tumour and Surgical Margin in a Group of
Patients with Oral Cavity Cancer.
AB - Oral cavity cancer belongs to head-and-neck squamous cell carcinoma group. The
purpose of the study was to assess the levels of certain proteins in a tumour and
surgical margin in a group of patients with oral cavity cancer. The levels of
DAPK1, MGMT, CDH1, SFRP1, SFRP2, RORA, TIMP3, p16, APC and RASSF1 proteins were
measured by ELISA in tissue homogenates. The protein levels of DAPK1, MGMT, CDH1,
SFRP2 and RASSF1 were significantly higher in tumour tissue than in the margin,
contrary to TIMP3 which was lower in the tumour itself. DAPK1 level in the tumour
was significantly higher in females than in males, the MGMT and p16 levels were
lower in the tumours with lymph node metastasis (N1 + N2) than in N0 samples. The
CDH1 expression was higher in a group with smoking habits, whereas TIMP3 was
lower in this group. Changes in the levels of proteins in tumour and surgical
margin may be either reflective of tumour occurrence and development, or they
might be also responsible for the progress and reoccurrence of the disease.
Levels of the studied proteins might be good prognostic factors; however, further
studies are required.
PMID- 28421311
TI - Long-term soil alteration in historical charcoal hearths affects Tuber
melanosporum mycorrhizal development and environmental conditions for fruiting.
AB - Abandoned charcoal hearths constitute a very particular habitat for spontaneous
fruiting of Tuber melanosporum, leading some harvesters to hypothesise that the
fungus could benefit from the alterations that these soils underwent. However,
ecological mechanisms involved in this relation are not fully elucidated yet. As
a first step to understand it, the influence of long-term soil alteration on the
symbiotic stage of T. melanosporum and on selected soil properties considered key
to fruiting was assessed by conducting a greenhouse bioassay and a field
observational study. In the bioassay, percent root colonisation and relative
abundance of T. melanosporum were significantly lower in hearth than in control
soils. Hearth soils showed significantly lower resistance to penetration, larger
temperature fluctuation, reduced plant cover and reduced herbaceous root
abundance. The results do not support the hypothesis that soil from historical
charcoal hearths currently enhances development of T. melanosporum mycorrhizas.
However, whether this is due to increased infectivity of native ectomycorrhizal
communities or to worse conditions for development of T. melanosporum mycorrhizas
remains unresolved. Native ectomycorrhizal communities in hearths showed altered
composition, although not a clear change in infectivity or richness. Direction of
change in hearth soil properties is compared to alteration occurring in soils
spontaneously producing T. melanosporum. The interest of these changes to improve
T. melanosporum fruiting in plantations is discussed.
PMID- 28421312
TI - An annotated translation of Noel Bernard's 1899 article 'On the germination of
Neottia nidus-avis'.
AB - We translate Noel Bernard's discovery of orchid symbiotic germination discovered
on Neottia nidus-avis, as published in the May 1899 issue of the Comptes rendus
hebdomadaires des seances de l'Academie des sciences. In his note, Bernard (1874
1911) establishes the need for a fungus, which is also forming mycorrhizae in
adults, for seeds germination. We provide illustrations reproduced from his later
works, and summaries of the French text he cited. In our annotations, we show how
early this discovery was done in Bernard's career, and insist on the scientific
framework at the end of the nineteenth century, where orchid germination was
mysterious and the need for vicinity of parents was not fully understood. We
comment the text of Bernard on the basis of the most recent knowledge on Neottia
nidus-avis and on orchid mycorrhizal fungi. Introducing his following papers, we
finally discuss the emergence of the concept of peloton digestion, and how
Bernard's work quickly paved the way to a general understanding of
mycoheterotrophic germination in orchids and beyond.
PMID- 28421313
TI - Association between forkhead-box P2 gene polymorphism and clinical symptoms in
chronic schizophrenia in a Chinese population.
AB - The forkhead-box P2 (FOXP2) gene polymorphism has been reported to be involved in
the susceptibility to schizophrenia; however, few studies have investigated the
association between FOXP2 gene polymorphism and clinical symptoms in
schizophrenia. This study investigated whether the FOXP2 gene was associated with
the development and symptoms of schizophrenia in relatively genetically
homogeneous Chinese population. The FOXP2 rs10447760 polymorphism was genotyped
in 1069 schizophrenia inpatients and 410 healthy controls using a case-control
design. The patients' psychopathology was assessed by the Positive and Negative
Syndrome Scale (PANSS). We found no significant differences in the genotype and
allele distributions between the patient and control groups. Interestingly, we
found significant differences in PANSS total, positive symptom, and general
psychopathology scores between genotypic subgroups in patients, with the higher
score in patients with CC genotype than those with CT genotype (all p < 0.05).
After adjusting demographic and clinical variables, the difference still remained
significant for the PANSS positive symptom score and general psychopathology
(both p < 0.05). Our findings suggest that the FOXP2 rs10447760 polymorphism may
not contribute to the development of schizophrenia, but may contribute to the
clinical symptoms of schizophrenia among Han Chinese.
PMID- 28421314
TI - The impact of body mass index on the risk of high spinal block in parturients
undergoing cesarean delivery: a retrospective cohort study.
AB - PURPOSE: To investigate the hypothesis that the risk of high spinal block is not
increased in obese parturients undergoing cesarean delivery compared to non-obese
parturients. METHODS: This is a retrospective study at an academic center. We
searched the perioperative database for women who underwent cesarean delivery
under spinal or combined spinal epidural anesthesia with hyperbaric bupivacaine
>=10.5 mg. A body mass index (BMI) >=30 kg/m2 was defined as obese. We
categorized obesity into: obesity class I (BMI = 30-34.9 kg/m2), obesity class II
(BMI = 35-39.9 kg/m2), obesity class III (BMI = 40-49.9 kg/m2), and super obese
(BMI >=50 kg/m2). The primary outcome was high spinal block defined as need to
convert to general anesthesia within 20 min of spinal placement as a result of
altered mental status, weakness, or respiratory distress resulting from the high
block, or a recorded block height >=T1. RESULTS: The analysis included 5015
women. High spinal blocks occurred in 29 patients (0.6%). The risk of high spinal
was significantly different according to BMI (p = 0.025). In a multivariate
model, BMI (p = 0.008) and cesarean delivery priority (p = 0.009) were associated
with high blocks. BMI >=50 kg/m2 was associated with greater odds of high block
compared to BMI <30 kg/m2 [odds ratio (95% confidence interval): 6.3 (2.2,
18.5)]. Scheduled cesarean delivery was also associated with greater odds of high
block compared with unscheduled delivery. CONCLUSIONS: At standard spinal doses
of hyperbaric bupivacaine used in our practice (>=10.5 mg), there were greater
odds of high block in those with BMI >=50 kg/m2.
PMID- 28421315
TI - In Reply: Similarities between parasternal intercostal nerve block and
subpectoral interfascial plane block.
PMID- 28421316
TI - Comparison of the coracoid and retroclavicular approaches for ultrasound-guided
infraclavicular brachial plexus block.
AB - PURPOSE: This prospective randomized study compared the coracoid and
retroclavicular approaches to ultrasound-guided infraclavicular brachial plexus
block (IBPB) in terms of needle tip and shaft visibility and quality of block. We
hypothesized that the retroclavicular approach would increase needle tip and
shaft visibility and decrease the number of needle passes compared to the
coracoid approach. METHODS: A total of 100 adult patients who received IBPB block
for upper limb surgery were randomized into two groups: a coracoid approach group
(group C) and a retroclavicular approach group (group R). In group C, the needle
was inserted 2 cm medial and 2 cm inferior to the coracoid process and directed
from ventral to dorsal. In group R, the needle insertion point was posterior to
the clavicle and the needle was advanced from cephalad to caudal. All ultrasound
images were digitally stored for analysis. The primary aim of the present study
was to compare needle tip and shaft visibility between the coracoid approach and
retroclavicular approach in patients undergoing upper limb surgery. The secondary
aim was to investigate differences between the two groups in the number of needle
passes, sensory and motor block success rates, surgical success rate, block
performance time, block performance-related pain, patient satisfaction, use of
supplemental local anesthetic and analgesic, and complications. RESULTS: Needle
tip visibility and needle shaft visibility were significantly better in group R
(p = 0.040, p = 0.032, respectively). Block performance time and anesthesia
related time were significantly shorter in group R (p = 0.022, p = 0.038,
respectively). Number of needle passes was significantly lower in group R (p =
0.044). Paresthesia during block performance was significantly higher in group C
(p = 0.045). There were no statistically significant differences between the two
groups in terms of sensory or motor block success, surgical success, block
related pain, and patient satisfaction. CONCLUSION: The retroclavicular approach
is associated with better needle tip and shaft visibility, reduced performance
time and anesthesia-related time, less paresthesia during block performance, and
fewer needle passes than the coracoid approach. TRiAL REGISTRY NUMBER:
Clinicaltrials.gov (no. NCT02673086).
PMID- 28421317
TI - Effect of oral carbohydrate with amino acid solution on serum oxidative/anti
oxidative status in healthy volunteers.
AB - The aim of this work was to investigate the effect of oral carbohydrate with
amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in
healthy persons. Fourteen healthy volunteers were segregated into control and ONS
groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle
Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the
day of the experiment. Volunteers in the control group fasted after dinner and
drank only water until 7:00 am on the day of the experiment. In both groups,
blood was collected at 9:00 am. The serum total oxidant levels and antioxidant
capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites)
test and BAP (biological antioxidant potential) test, respectively. In the ONS
group, the serum d-ROMs level was significantly lower than in the control group
(297 +/- 43 and 327 +/- 41 U.CARR, respectively, p = 0.018), while the serum BAP
level was significantly higher than the control group (2410 +/- 432 and 1979 +/-
397 umol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much
higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that
an ONS with arginine loading could decrease oxidative stress and increase
antioxidant capacity in healthy volunteers.
PMID- 28421318
TI - Mental Health Care Use in Children of Parents with Mental Health Problems:
Results of the BELLA Study.
AB - Whether parental mental health problems facilitate or hinder the use of mental
health care of the parents' children is still unclear. The present cross
sectional study examined mental health care use and potential predictors in a
population based sample. Children of parents with mental health problems (CPM)
were nearly 5 times more likely to use mental health care compared to children of
parents without mental health problems. A multiple regression analysis revealed
that the most important predictors of mental health care use for CPM were active
family life (OR = 2.67) and children's own mental health problems (OR = 1.18 self
report, 1.17 parent-report). Additionally, parental strain showed a tendency to
predict mental health care use (OR = 2.45). This study demonstrates that parental
mental health problems are associated with mental health care use in their
children and that improving certain family factors may support children's mental
health care use.
PMID- 28421319
TI - Inferior vena cava segmentation with parameter propagation and graph cut.
AB - PURPOSE: The inferior vena cava (IVC) is one of the vital veins inside the human
body. Accurate segmentation of the IVC from contrast-enhanced CT images is of
great importance. This extraction not only helps the physician understand its
quantitative features such as blood flow and volume, but also it is helpful
during the hepatic preoperative planning. However, manual delineation of the IVC
is time-consuming and poorly reproducible. METHODS: In this paper, we propose a
novel method to segment the IVC with minimal user interaction. The proposed
method performs the segmentation block by block between user-specified beginning
and end masks. At each stage, the proposed method builds the segmentation model
based on information from image regional appearances, image boundaries, and a
prior shape. The intensity range and the prior shape for this segmentation model
are estimated based on the segmentation result from the last block, or from user-
specified beginning mask if at first stage. Then, the proposed method minimizes
the energy function and generates the segmentation result for current block using
graph cut. Finally, a backward tracking step from the end of the IVC is performed
if necessary. RESULTS: We have tested our method on 20 clinical datasets and
compared our method to three other vessel extraction approaches. The evaluation
was performed using three quantitative metrics: the Dice coefficient (Dice), the
mean symmetric distance (MSD), and the Hausdorff distance (MaxD). The proposed
method has achieved a Dice of [Formula: see text], an MSD of [Formula: see text]
mm, and a MaxD of [Formula: see text] mm, respectively, in our experiments.
CONCLUSION: The proposed approach can achieve a sound performance with a
relatively low computational cost and a minimal user interaction. The proposed
algorithm has high potential to be applied for the clinical applications in the
future.
PMID- 28421320
TI - Hepatocyte-specific depletion of ubiquitin regulatory X domain containing protein
8 accelerates fibrosis in a mouse non-alcoholic steatohepatitis model.
AB - Ubiquitin regulatory X domain-containing protein 8 (UBXD8) is engaged in the
degradation of lipidated apolipoprotein B in hepatocytes. We previously showed
that hepatocyte-specific UBXD8-deficient mice (U8-HKO) fed a moderately high-fat
diet (31 kcal % fat) showed periportal macrovesicular steatosis along with a
decrease in very low-density lipoprotein secretion, but did not develop fibrosis.
In the present study, we examined whether U8-HKO mice show NASH-like phenotypes
when fed a very high-fat diet (60 kcal % fat). U8-HKO mice and their age-matched
littermates (control) were fed with two NASH model diets: choline-sufficient very
high-fat diet and choline-deficient very high-fat diet. After being fed a very
high-fat diet for 2 weeks, U8-HKO mice showed hepatic fibrosis in a significantly
wider area than in the control. Fibrosis in U8-HKO mouse liver was further
enhanced under a very high-fat diet depleted of choline (the liver surface was
lumpy). Concomitant administration of an angiotensin 2 type 1 receptor blocker
reduced the hepatic fibrosis caused by the very high-fat diet, suggesting the
existence of inflammation. Carbon tetrachloride also induced hepatic fibrosis but
the severity was comparable in the control and U8-HKO mice. In conjunction with
our previous finding, the results indicate that although UBXD8 functionality can
be largely compensated in the normal setting, it is crucial to sustain VLDL
secretion when exposed to a dietary challenge of high fat. U8-HKO mice that
develop fibrosis within 2 weeks of high-fat feeding can be used as a model to
study NAFLD/NASH disease progression.
PMID- 28421321
TI - Experimental Investigations on Fluorescence Excitation and Depletion of Carbon
Dots.
AB - Carbon dots (CDs) can be readily synthesized and utilized as attractive
fluorescent probes for a variety of applications. In this study, we have
synthesized CDs using a previously published method and characterized their photo
physical properties. The resultant CDs possess prominent photo-stability and
short emission wavelength in the violet region. Our study reveals that CDs, with
weak photo-bleaching, enable them to be employed to achieve high spatial
resolution in stimulated emission depletion (STED) microscopy. The depletion
efficiency can reach 60%. More importantly, the shorter excitation wavelength of
CDs contributes to further improvement of resolution for STED microscopy. An
excellent candidate for fluorophores, these CDs have potential to be used in
super-resolution imaging for STED microscopy.
PMID- 28421322
TI - A Colorimetric and Fluorescent Probe Based on Michael Acceptor Type
Diketopyrrolopyrrole for Cyanide Detection.
AB - A new probe 1 was synthesized by incorporating an alpha,beta-unsaturated ketone
to a diketopyrrolopyrrole fluorophore. The probe exhibited a selective and
sensitive response to cyanide against other anions. Addition of CN- aqueous
solution to 1 resulted in a rapid color change from pink to light yellow together
with a blue shift from 518 to 421 nm, while other anions did not induce any
significant color change. Furthermore, the Michael addition of cyanide to 1
elicited 98% fluorescence quenching at 608 nm, which constituted the fluorescence
signature for cyanide detection. The detection limit was 0.67 MUM using the
fluorescence spectra changes, which was far lower than the WHO guideline of 1.9
MUM. Moreover, 1-based test strips could successfully detect CN- solutions.
PMID- 28421323
TI - Gene expression, nucleotide composition and codon usage bias of genes associated
with human Y chromosome.
AB - Analysis of codon usage pattern is important to understand the genetic and
evolutionary characteristics of genomes. We have used bioinformatic approaches to
analyze the codon usage bias (CUB) of the genes located in human Y chromosome.
Codon bias index (CBI) indicated that the overall extent of codon usage bias was
low. The relative synonymous codon usage (RSCU) analysis suggested that
approximately half of the codons out of 59 synonymous codons were most frequently
used, and possessed a T or G at the third codon position. The codon usage pattern
was different in different genes as revealed from correspondence analysis (COA).
A significant correlation between effective number of codons (ENC) and various GC
contents suggests that both mutation pressure and natural selection affect the
codon usage pattern of genes located in human Y chromosome. In addition, Y-linked
genes have significant difference in GC contents at the second and third codon
positions, expression level, and codon usage pattern of some codons like the
SPANX genes in X chromosome.
PMID- 28421324
TI - Weathering the storm: how lodgepole pine trees survive mountain pine beetle
outbreaks.
AB - Recent mountain pine beetle outbreaks in western North America killed millions of
lodgepole pine trees, leaving few survivors. However, the mechanism underlying
the ability of trees to survive bark beetle outbreaks is unknown, but likely
involve phytochemicals such as monoterpenes and fatty acids that can drive beetle
aggregation and colonization on their hosts. Thus, we conducted a field survey of
beetle-resistant lodgepole pine (Pinus contorta) trees to retrospectively deduce
whether these phytochemicals underlie their survival by comparing their chemistry
to that of non-attacked trees in the same stands. We also compared beetle attack
characteristics between resistant and beetle-killed trees. Beetle-killed trees
had more beetle attacks and longer ovipositional galleries than resistant trees,
which also lacked the larval establishment found in beetle-killed trees.
Resistant trees contained high amounts of toxic and attraction-inhibitive
compounds and low amounts of pheromone-precursor and synergist compounds. During
beetle host aggregation and colonization, these compounds likely served three
critical roles in tree survival. First, low amounts of pheromone-precursor (alpha
pinene) and synergist (mycrene, terpinolene) compounds reduced or prevented
beetles from attracting conspecifics to residual trees. Second, high amounts of 4
allyanisole further inhibited beetle attraction to its pheromone. Finally, high
amounts of toxic limonene, 3-carene, 4-allyanisole, alpha-linolenic acid, and
linoleic acid inhibited beetle gallery establishment and oviposition. We conclude
that the variation of chemotypic expression of local plant populations can have
profound ecological consequences including survival during insect outbreaks.
PMID- 28421325
TI - Plant-microbial competition for nitrogen increases microbial activities and
carbon loss in invaded soils.
AB - Many invasive plant species show high rates of nutrient acquisition relative to
their competitors. Yet the mechanisms underlying this phenomenon, and its
implications for ecosystem functioning, are poorly understood, particularly in
nutrient-limited systems. Here, we test the hypothesis that an invasive plant
species (Microstegium vimineum) enhances its rate of nitrogen (N) acquisition by
outcompeting soil organic matter-degrading microbes for N, which in turn
accelerates soil N and carbon (C) cycling. We estimated plant cover as an
indicator of plant N acquisition rate and quantified plant tissue N, soil C and N
content and transformations, and extracellular enzyme activities in invaded and
uninvaded plots. Under low ambient N availability, invaded plots had 77% higher
plant cover and lower tissue C:N ratios, suggesting that invasion increased rates
of plant N acquisition. Concurrent with this pattern, we observed significantly
higher mass-specific enzyme activities in invaded plots as well as 71% higher
long-term N availability, 21% lower short-term N availability, and 16% lower
particulate organic matter N. A structural equation model showed that these
changes were interrelated and associated with 27% lower particulate organic
matter C in invaded areas. Our findings suggest that acquisition of N by this
plant species enhances microbial N demand, leading to an increased flux of N from
organic to inorganic forms and a loss of soil C. We conclude that high N
acquisition rates by invasive plants can drive changes in soil N cycling that are
linked to effects on soil C.
PMID- 28421326
TI - Nutrient enrichment in water more than in leaves affects aquatic microbial litter
processing.
AB - Nutrient enrichment of soils and water will intensify in the future and has the
potential to alter fundamental ecosystem processes, such as litter decomposition.
We tested the direct (via water nutrient enrichment) and indirect (via changes in
leaf chemistry) effects of nutrient enrichment on microbial activity and
decomposability of Quercus robur L. (oak) leaves in laboratory microcosms
simulating streams. Senescent leaves of oak trees grown without and with
fertilization were incubated under ambient and elevated water nutrient [nitrogen
(N) and phosphorus (P)] concentrations for 60 days. Soil fertilization led to an
increase in leaf (3.4*) and leaf litter (2.3*) N concentration. Increased water
dissolved nutrients concentrations stimulated microbial activity (N uptake,
microbial respiration, fungal biomass buildup and conidia production by aquatic
hyphomycetes) that translated into accelerated litter decomposition (2.1* for
unfertilized and 1.6* for fertilized trees). Leaves from fertilized trees had
higher microbial activity and decomposition rates than leaves from unfertilized
trees only at low dissolved nutrient availability. When both litter and water
nutrients concentration increased, microbial activity and leaf decomposition were
stimulated, but the effects were additive and direct effects from increased
dissolved nutrient availability were stronger than those mediated by increases in
litter N concentration (indirect effects). Our results suggest that increases in
water nutrient availability (within the range used in this study) may exert a
stronger control on microbial activity and litter decomposition than litter
nutrient enrichment.
PMID- 28421327
TI - Metal-DNA Interactions Improve signal in High-Resolution Melting of DNA for
Species Differentiation of Plasmodium Parasite.
AB - The success of high-resolution melting (HRM) analysis for distinguishing similar
DNAs with minor base mismatch differences is limited. Here, metal-mediated
structural change in DNA has been exploited to amplify HRM signals leading to
differentiation of target DNAs in an orthologous gene corresponding to four
Plasmodium species. Conserved 26-mer ssDNAs from ldh gene of the four Plasmodium
species were employed as targets. A capture probe (CP) that is fully
complementary to the Plasmodium falciparum target (FT) and has two base
mismatches each, with the targets of Plasmodium vivax (VT), Plasmodium malariae,
(MT), and Plasmodium ovale (OT), was considered. The DNA duplexes were treated
with metal ions for structural perturbation and analyzed by HRM. Distinct
resolution of melting fluorescence signal in otherwise identical HRM profiles for
each of the DNA duplexes was achieved by using Ca+2 or Mg+2 ions, where, Ca+2
conferred higher resolution. The increase in resolution for CP-FT versus CP-OT,
CP-FT versus CP-VT, CP-FT versus CP-MT, CP-VT versus CP-OT, and CP-MT versus CP
OT with Ca-DNA as compared to control was 67.3-, 20.4-, 22.0-, 10.9-, and 8.3
fold, respectively. The signal resolution was the highest at pH 8. The method
could detect 0.25 pmol/ul of the target DNA. Structural analysis showed that Ca+2
and Mg+2 ions perturbed the structure of DNA. This perturbation helped to improve
HRM signal resolution among DNA targets corresponding to the orthologous gene of
four Plasmodium species. This novel approach has potential application not only
for Plasmodium species-specific diagnosis but also for differentiation of DNAs
with minor sequence variation.
PMID- 28421328
TI - Association of adiponectin, leptin and resistin with inflammatory markers and
obesity in dementia.
AB - The aim of the study was to determine the role of adiponectin, leptin and
resistin in various types of dementia and to investigate their association with
inflammatory markers, insulin resistance and abdominal obesity. In 205 patients
with dementia [89 with Alzheimer's disease (AD), 47 with vascular dementia (VaD),
69 with mixed dementia (MD)], 113 persons with mild cognitive impairment and in
107 controls serum adiponectin, leptin and resistin levels, pro-inflammatory
[interleukin-6 (IL-6), C-reactive protein (hsCRP) and chitotriosidase] and anti
inflammatory (25-OH vitamin D, HDL-cholesterol and paraoxonase 1) markers, as
well as glucose metabolism parameters (glucose, insulin and HOMA-IR) were
determined. In all-cause dementia adiponectin and resistin levels were
significantly higher as compared to the controls; leptin levels did not show
differences. Higher adiponectin levels concerned AD and MD, whereas higher
resistin-VaD and MD. After stratification by abdominal obesity the differences in
adiponectin levels remained significant in subjects without obesity. In all-cause
dementia negative correlation of adiponectin with obesity, glucose metabolism
parameters, IL-6 and hsCRP and positive correlation with HDL-cholesterol were
found. Positive correlation of resistin with age, IL-6, hsCRP and chitotriosidase
and negative correlation with HDL-cholesterol and paraoxonase 1 were stated. We
conclude that dementia of neurodegenerative origin is characterized by elevated
adiponectin levels, whereas dementia with vascular changes by increase of
resistin. Association with inflammatory indicators may suggest the pro
inflammatory role of resistin in the development of dementia, especially in
dementia of vascular mechanism. Identification of this novel biomarker may be
important in preventing dementia.
PMID- 28421329
TI - Characterization of two TT2-type MYB transcription factors regulating
proanthocyanidin biosynthesis in tetraploid cotton, Gossypium hirsutum.
AB - MAIN CONCLUSION: Two TT2-type MYB transcription factors identified from
tetraploid cotton are involved in regulating proanthocyanidin biosynthesis,
providing new strategies for engineering condensed tannins in crops.
Proanthocyanidins (PAs), also known as condensed tannins, are important secondary
metabolites involved in stress resistance in plants, and are health supplements
that help to reduce cholesterol levels. As one of the most widely grown crops in
the world, cotton provides the majority of natural fabrics and is a supplemental
food for ruminant animals. The previous studies have suggested that PAs present
in cotton are a major contributor to fiber color. However, the biosynthesis of
PAs in cotton still remains to be elucidated. AtTT2 (transparent testa 2) is a
MYB family transcription factor from Arabidopsis that initiates the biosynthesis
of PAs by inducing the expression of multiple genes in the pathway. In this
study, we isolated two R2R3-type MYB transcription factors from Gossypium
hirsutum that are homologous to AtTT2. Expression analysis showed that both genes
were expressed at different levels in various cotton tissues, including leaf,
seed coat, and fiber. Protoplast transactivation assays revealed that these two
GhMYBs were able to activate promoters of genes encoding enzymes in the PA
biosynthesis pathway, namely anthocyanidin reductase and leucoanthocyanidin
reductase. Complementation experiments showed that both of the GhMYBs were able
to recover the transparent testa seed coat phenotype of the Arabidopsis tt2
mutant by restoring PA biosynthesis. Ectopic expression of either of the two
GhMYBs in Medicago truncatula hairy roots increased the contents of anthocyanins
and PAs compared to control lines expressing the GUS gene, and expression levels
of MtDFR, MtLAR, and MtANR were also elevated in lines expressing GhMYBs.
Together, these data provide new insights into engineering condensed tannins in
cotton.
PMID- 28421330
TI - Regulation of CONIFERALDEHYDE 5-HYDROXYLASE expression to modulate cell wall
lignin structure in rice.
AB - MAIN CONCLUSION: Regulation of a gene encoding coniferaldehyde 5-hydroxylase
leads to substantial alterations in lignin structure in rice cell walls,
identifying a promising genetic engineering target for improving grass biomass
utilization. The aromatic composition of lignin greatly affects utilization
characteristics of lignocellulosic biomass and, therefore, has been one of the
primary targets of cell wall engineering studies. Limited information is,
however, available regarding lignin modifications in monocotyledonous grasses,
despite the fact that grass lignocelluloses have a great potential for feedstocks
of biofuel production and various biorefinery applications. Here, we report that
manipulation of a gene encoding coniferaldehyde 5-hydroxylase (CAld5H, or
ferulate 5-hydroxylase, F5H) leads to substantial alterations in syringyl
(S)/guaiacyl (G) lignin aromatic composition in rice (Oryza sativa), a major
model grass and commercially important crop. Among three CAld5H genes identified
in rice, OsCAld5H1 (CYP84A5) appeared to be predominantly expressed in lignin
producing rice vegetative tissues. Down-regulation of OsCAld5H1 produced altered
lignins largely enriched in G units, whereas up-regulation of OsCAld5H1 resulted
in lignins enriched in S units, as revealed by a series of wet-chemical and NMR
structural analyses. Our data collectively demonstrate that OsCAld5H1 expression
is a major factor controlling S/G lignin composition in rice cell walls. Given
that S/G lignin composition affects various biomass properties, we contemplate
that manipulation of CAld5H gene expression represents a promising strategy to
upgrade grass biomass for biorefinery applications.
PMID- 28421331
TI - Two Troubling Trends in the Conversation Over Whether Clinical Ethics Consultants
Have Ethics Expertise.
AB - In a recent issue of the Journal of Medicine and Philosophy, several scholars
wrote on the topic of ethics expertise in clinical ethics consultation. The
articles in this issue exemplified what we consider to be two troubling trends in
the quest to articulate a unique expertise for clinical ethicists. The first
trend, exemplified in the work of Lisa Rasmussen, is an attempt to define a role
for clinical ethicists that denies they have ethics expertise. Rasmussen cites
the dependence of ethical expertise on irresolvable meta-ethical debates as the
reason for this move. We argue against this deflationary strategy because it ends
up smuggling in meta-ethical assumptions it claims to avoid. Specifically, we
critique Rasmussen's distinction between the ethical and normative features of
clinical ethics cases. The second trend, exemplified in the work of Dien Ho, also
attempts to avoid meta-ethics. However, unlike Rasmussen, Ho tries to articulate
a notion of ethics expertise that does not rely upon meta-ethics. Specifically,
we critique Ho's attempts to explain how clinical ethicists can resolve moral
disputes using what he calls the "Default Principle" and "arguments by parity."
We show that these strategies do not work unless those with the moral
disagreement already share certain meta-ethical assumptions. Ultimately, we argue
that the two trends of (1) attempting to avoid meta-ethics by denying that
clinical ethicists have ethics expertise, and (2) attempting to articulate how
ethics expertise can be used to resolve disputes without meta-ethics both fail
because they do not, in fact, avoid doing meta-ethics. We conclude that these
trends detract from what clinical ethics consultation was founded to do and ought
to still be doing-provide moral guidance, which requires ethics expertise, and
engagement with meta-ethics. To speak of ethicists without ethics expertise
leaves their role in the clinic dangerously unclear and unjustified.
PMID- 28421332
TI - The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for
Clinical Use, Content Validation, and Inter-rater Reliability.
AB - PURPOSE: The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a
method for assessing the likelihood that a patient's muscle symptoms (e.g.,
myalgia or myopathy) were caused or worsened by statin use. The objectives of
this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater
reliability, and collect feedback from physicians on its practical application.
METHODS: For content validity, we conducted structured in-depth interviews with
its original authors as well as with a panel of independent physicians.
Estimation of inter-rater reliability involved an analysis of 30 written clinical
cases which were scored by a sample of physicians. A separate group of physicians
provided feedback on the clinical use of the SAMS-CI and its potential utility in
practice. RESULTS: Qualitative interviews with providers supported the content
validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included
several perceived benefits (such as brevity, clear wording, and simple scoring
process) and some possible concerns (workflow issues and applicability in primary
care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77
(confidence interval 0.66-0.85), indicating high concordance between raters. With
additional provider feedback, a revised SAMS-CI instrument was created suitable
for further testing, both in the clinical setting and in prospective validation
studies. CONCLUSIONS: With standardized questions, vetted language, easily
interpreted scores, and demonstrated reliability, the SAMS aims to estimate the
likelihood that a patient's muscle symptoms were attributable to statins. The
SAMS-CI may support better detection of statin-associated muscle symptoms in
clinical practice, optimize treatment for patients experiencing muscle symptoms,
and provide a useful tool for further clinical research.
PMID- 28421334
TI - Guideline adherence of antidepressant treatment in outpatients with major
depressive disorder: a naturalistic study.
AB - Little is known about guideline adherence of naturalistic antidepressant drug
therapy in outpatients with major depressive disorder (MDD). The aim of the study
was to analyze guideline adherence, especially regarding treatment length,
treatment evaluation and medication change strategies. We investigated 889
patients with MDD who had been admitted for inpatient treatment and were enrolled
in the early medication change trial (ClinicalTrials.gov NCT00974155). We
investigated all patients at screening visit regarding previous outpatient drug
treatment in the index episode, which was assessed by structured interviews.
Demographic variables were obtained from patients and patients' records. 51.0% of
the patients had received previous drug treatment in the index episode, 56.6%
were females, and their mean age was 40.0 years. In the 153 patients who were
pharmacologically treated at least 8 weeks, medication was not changed in 129
(84.3%) patients. Patients who had a medication change in their index episode (n
= 24, 15.7%) waited 71.1 weeks (+/-110.4) for their treatment optimization. Only
5 of those 153 patients (3.3%) had a dose increase, whereas 132 patients (86.3%)
had no dose adaption at all. Antidepressant blood levels were measured in 46
patients (30.1%). We conclude that a large proportion of patients with MDD is not
treated in adherence to treatment guidelines recommending treatment evaluation
(e.g. therapeutic drug monitoring) and treatment change after 4 to 8 weeks in non
responders. Earlier treatment optimization may prevent long-term suffering of
patients and may avoid inpatient treatment.
PMID- 28421333
TI - Identification of putative second genetic hits in schizophrenia carriers of high
risk copy number variants and resequencing in additional samples.
AB - Copy number variants (CNVs) conferring risk of schizophrenia present incomplete
penetrance, suggesting the existence of second genetic hits. Identification of
second hits may help to find genes with rare variants of susceptibility to
schizophrenia. The aim of this work was to search for second hits of
moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the
relevant genes in additional samples. To this end, ten patients with risk CNVs at
cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole
exome sequencing. Rare single nucleotide variants, defined as those absent from
main public databases, were classified according to bioinformatic prediction of
pathogenicity by CADD scores. The average number of rare predicted pathogenic
variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare
predicted pathogenic variants in more than one sample. Follow-up resequencing of
these genes in 432 additional cases and 432 controls identified a significant
excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking
into account its function in clathrin-mediated synaptic vesicle endocytosis at
presynaptic terminals, our results suggest an impairment of this process in
schizophrenia.
PMID- 28421335
TI - Effect of statins on hospitalization risk of bacterial infections in patients
with or without diabetes.
AB - AIMS: To investigate whether statins reduce the risk to first hospitalization of
bacterial infections, in patients with or without diabetes taking into account
prior or incident comorbidities. METHODS: By using administrative databases, the
effect of current statin use was measured on the risk of first hospitalizations
due to bacterial infections in people living in Tuscany, Italy, in the period
January 1, 2011-December 31, 2015, after excluding those with previous statins
use. Population was stratified as with (n = 128,207) or without diabetes (n =
3,304,906), and the hospitalization risk was analyzed by a Cox proportional
hazards regression analysis after adjusting for age, gender, previous
comorbidities, chronic renal failure, and prior or incident cardiovascular
diseases. RESULTS: During the 5-year follow-up, 31,543 hospitalizations for
bacterial infections were observed: 2.08(2.06-2.10) per 1000 person-year in non
diabetic and 5679: 9.13(8.94-9.32) per 1000 person-year in diabetic population.
Diabetes conferred a greater risk of hospitalizations, independently from
confounders [adjusted HR (95% CI) 2.04 (1.97-2.10); P < 0.0001]. Statin use
decreased the risk by about 2.5% for each one month of therapy, at the same
extent in subjects with or without diabetes, after adjusting for all covariates.
CONCLUSIONS: In this population, diabetes was associated by a twofold increase in
the 5-year risk of hospitalizations for bacterial infections. Statin use
decreased this risk to a same extent in subjects without or with diabetes, after
adjusting for main confounders including comorbidities, and previous or incident
cardiovascular events.
PMID- 28421336
TI - Achievement of metabolic control among children and adolescents with type 1
diabetes in Spain.
AB - AIMS: To assess metabolic control in a paediatric T1D population in Spain and
analyse the rate of severe acute decompensations and chronic complications.
METHODS: Data from patients treated at eight paediatric diabetes units with
experienced diabetes teams between June and December 2014 were analysed in an
observational prospective study. Variables included: age, sex, diabetes duration,
number of follow-up visits/year, anthropometrical data, insulin treatment
modalities, mean annual HbA1c and the prevalence of acute and chronic
complications. SPSS statistics 21.0 was used. RESULTS: A total of 853 patients
(49.7% female) with a mean age of 12.1 +/- 3.7 years were included.
Anthropometric data were normal. Mean diabetes duration was 8 +/- 3.4 years. Mean
outpatient follow-up was 4.7 +/- 0.04 visits/year. Twenty-five per cent were on
continuous subcutaneous insulin infusion (CSII). Mean HbA1c was 7.3 +/- 1% (56 +/
8 mmol/mol) and 66.6% had HbA1c < 7.5% (58 mmol/mol). HbA1c value correlated
negatively with age at onset and positively with years of diabetes, number of
visits/year and current age (F = 7.06; p = 0.01). Patients on CSII (n = 213) were
younger, attended the outpatient clinic more frequently, were diagnosed earlier,
had better metabolic control and had presented more severe hypoglycaemic episodes
the previous year. The rate of severe decompensation (episodes/100 patients/year)
was ketoacidosis 1.5 and severe hypoglycaemia 4.5. The prevalence of chronic
complications was very low. CONCLUSIONS: Our data describe the good compliance of
paediatric T1D patients treated at eight paediatric units in Spain following
international standards of metabolic control.
PMID- 28421337
TI - Glucose-independent association of adiposity and diet composition with
cardiovascular risk in children and adolescents with type 1 diabetes.
AB - AIMS: To test the hypothesis that diet composition, adiposity and glycometabolic
control could independently contribute to an increase in the cardiovascular risk
(CVR) for children/adolescents with type 1 diabetes (T1D). METHODS: One hundred
and eighty children/adolescents with T1D (age range 5-18 years) were enrolled.
Diet (3-day weighed dietary record), physical (height, weight, waist
circumference, bioelectrical impedance analysis) and biochemical (HbA1c, lipid
profile) parameters were recorded. Regression models, using non-HDL cholesterol
(a gross index of CVR) as the dependent variable and HbA1c (mmol/mol), fat mass
(FM) %, lipid-to-carbohydrate intake ratio as independent ones, were calculated.
RESULTS: Non-HDL cholesterol was significantly associated with adiposity (FM%; r
= 0.27, 95% CI 0.13-0.43), body fat distribution (waist-to-height ratio; r =
0.16, 95% CI 0.02-0.31), lipid intake [% of energy intake (EI)] (r = 0.25, 95% CI
0.11-0.41), carbohydrate intake (% EI; r = -0.24, 95% CI 0.10-0.40), lipid-to
carbohydrate intake ratio (r = 0.26, 95% CI 0.12-0.42) and blood glucose control
(HbA1c; r = 0.24, 95% CI 0.10-0.40). A p value cutoff of 0.10 was used for
covariates to be included in the regression analysis. Multiple regression
analysis showed that adiposity (FM%), blood glucose control (HbA1c) and lipid-to
carbohydrate intake ratio independently contributed to explaining the inter
individual variability of non-HDL cholesterol (R 2 = 0.163, p < 0.05).
CONCLUSIONS: Adiposity and lipid-to-carbohydrate intake ratio affect non-HDL
cholesterol, a gross index of CVR, regardless of HbA1c, in children and
adolescents with T1D. Intervention to reduce CVR in T1D patients should focus not
only on glycometabolic control but also on adiposity and diet composition.
PMID- 28421338
TI - Tailoring pharmacotherapy to specific eating behaviours in obesity: Can
recommendations for personalised therapy be made from the current data?
AB - Pharmacotherapy provides an adjunct to behaviour modification in the management
of obesity. There are a number of new drug therapies purportedly targeting
appetite; liraglutide, and bupropion/naltrexone, which are European Medicines
Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and
phentermine/topiramate, which have FDA approval only. Each of the six drugs, used
singly or in combination, has distinct pharmacological, and presumably distinct
behavioural, mechanisms of action, thus the potential to provide defined
therapeutic options to personalise the management of obesity. Yet, with regard to
pharmacotherapy for obesity, we are far from true personalised medicine. We
review the limited mechanistic data with four mono and combination
pharmacotherapies, to assess the potential for tailoring their use to target
specific obesogenic behaviours. Potential treatment options are considered, but
in the absence of adequate research in respect to effects of these drugs on
eating behaviour, neural activity and psychological substrates that underlie
poorly controlled eating, we are far from definitive therapeutic recommendations.
Specific mechanistic studies and broader behavioural phenotyping, possibly in
conjunction with pharmacogenetic research, are required to characterise
responders for distinct pharmacotherapeutic options.
PMID- 28421339
TI - Small bowel adenocarcinoma complicating Crohn's disease: a single-centre
experience emphasizing the importance of screening for dysplasia.
AB - Small bowel adenocarcinoma (SBA) complicating Crohn's disease (CD) is rare and
generally found incidentally on surgical specimens. We report our experience in
CD-associated SBA observed this last decade in a tertiary referral centre in
order to update its incidence, clinical presentation and pathological features.
All SBAs diagnosed in patients who underwent surgery for CD between 2006 and 2016
were retrospectively included. Clinico-pathological characteristics were
reviewed, and follow-up was updated. SBA was diagnosed in 9 (1.7%) of 522
patients who underwent SB resection(s) after a median CD duration of 15 years [0
32]. The median age at diagnosis was 46 years. Seven (78%) patients had
obstructive symptoms refractory to medical treatment. Pre-operative biopsy
revealed neoplasia in five (56%) patients (dysplasia in three and SBA in two)
justifying the surgery. Two (29%) of the seven patients with imaging had features
suggestive of cancer. In all specimens, SBA developed in active ileitis with
adjacent dysplasia. Stage I low-grade tubulo-glandular adenocarcinoma was
observed in 33% of patients. Stage IV high-grade adenocarcinoma was observed in
56% of patients, and mucinous/signet ring cell differentiation predominated in
44% of patients. Molecular analysis showed no BRAF mutation, a KRAS mutation in
one case and a microsatellite instability phenotype suggestive of Lynch syndrome
in one case. After a median follow-up of 24 months [7-82], four (44%) patients
died with advanced stage IV SBA. This surgical series confirms that CD-associated
SBA is rare with an incidence of 1.7%. Adjacent dysplasia was present in all
specimens and was identified before surgery in all patients who benefit from
ileal biopsies. This strengthens the importance of screening all longstanding CD
by endoscopy if surgery is not considered.
PMID- 28421340
TI - Is tumor cellularity in primary invasive breast carcinoma of prognostic
significance?
AB - Many methods of analysis to predict survival of invasive mammary carcinoma in the
post-neoadjuvant setting utilize tumor cellularity alone or in combination with
other tumor features. The goal of this study was to evaluate the prognostic value
of tumor cellularity in primary non-treated carcinoma. We used 366 cases of
invasive breast carcinoma to determine invasive tumor cellularity (%) by
reviewing a representative excisional tumor section and correlated this with
breast cancer recurrence (BCR) and overall mortality (OM). Mean patient age was
58 years (range, 21-91) and median follow-up was 87 months (range, 0.7-165). Of
the cases, 25% were Nottingham grades I, 41% grade II, and 32% grade III. The
Nottingham Prognostic Index (NPI) ranged from 2.06 to 6.8 (mean 3.93). Estrogen
receptor was positive in 66% and negative in 25% of cases. Cellularity ranged
from 2 to 99% (mean 47.6%). The OM hazard ratio increased by 1.73 for every unit
increase in NPI (P < 0.00005; 95% confidence interval 1.45-2.05) The BCR hazard
ratio increased by 2.011 for every unit increase in NPI BCR (P < 0.00005; 95%
confidence interval 1.62-2.50). Cellularity, unadjusted for other covariates, was
not significantly associated with either OM or BCR. When adjusted for NPI,
cellularity still showed no significant relation to OM or BCR. The same analysis
performed on estrogen receptor-positive and estrogen receptor-negative subgroups
continued to show no relation between cellularity and OM or BCR. In conclusion,
despite its utility in the neoadjuvant setting, we were unable to show that
cellularity is predictive of survival in primary breast carcinomas.
PMID- 28421341
TI - Insufficient activation of Akt upon reperfusion because of its novel modification
by reduced PP2A-B55alpha contributes to enlargement of infarct size by chronic
kidney disease.
AB - Chronic kidney disease (CKD) increases myocardial infarct size by an unknown
mechanism. Here we examined the hypothesis that impairment of protective PI3K
PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced
enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx
group) 4 weeks before myocardial infarction experiments, and sham-operated rats
served as controls (Sham group). Infarct size as a percentage of area at risk
after ischemia/reperfusion was significantly larger in the SNx group than in the
Sham group (56.3 +/- 4.6 vs. 41.4 +/- 2.0%). In SNx group, myocardial p-Akt
Thr308 level at baseline was elevated, and reperfusion-induced phosphorylation of
p-Akt-Ser473, p-p70s6K and p-GSK-3beta was significantly suppressed. Inhibition
of Akt-Ser473 phosphorylation upon reperfusion by Ku-0063794 significantly
increased infarct size in the Sham group but not in the SNx group. There was no
difference between the two groups in activities of mTORC2 and PDK1 and protein
level of PTEN. However, the PP2A regulatory subunit B55alpha, which specifically
targets Akt-Thr308, was reduced by 24% in the SNx group. Knockdown of B55alpha by
siRNA increased baseline p-Akt-Thr308 and blunted Akt-Ser473 phosphorylation in
response to insulin-like growth factor-1 (IGF-1) in H9c2 cells. A blunted
response of Akt-Ser473 to IGF-1 was also observed in HEK293 cells transfected
with a p-Thr308-mimetic Akt mutant (T308D). These results indicate that increased
Akt-Thr308 phosphorylation by down-regulation of B55alpha inhibits Akt-Ser473
phosphorylation upon reperfusion in CKD and that the impaired Akt activation by
insufficient Ser473 phosphorylation upon reperfusion contributes to infarct size
enlargement by CKD.
PMID- 28421342
TI - Selective retina therapy with automatic real-time feedback-controlled dosimetry
for chronic central serous chorioretinopathy in Korean patients.
AB - PURPOSE: To evaluate the safety and efficacy of selective retina therapy (SRT)
with real-time feedback-controlled dosimetry (RFD) in the treatment of chronic
central serous chorioretinopathy (CSC). METHODS: In this retrospective case
series study, 50 eyes of 49 patients with chronic CSC demonstrating focal or
diffuse foveal leakages on fundus fluorescein angiography (FFA) were included.
Following evaluation of test spots at temporal arcades, SRT (wavelength 527 nm,
pulse repetition rate 100 Hz, pulse energy ramp with maximal 15 pulses) with
retinal spot diameter of 200 MUm was applied to the areas of each leakage
observed on fluorescein angiography. Changes in mean best corrected visual acuity
(BCVA), maximum macular thickness (MMT), subretinal fluid (SRF) height, and
subfoveal choroidal thickness (SCT) were evaluated at 1, 2 and 3 months after
treatment. RFD was used for adjusting the pulse energy. Eyes received a mean of
21.1 +/- 18.1 treatment spots with a range of energies between 50uJ and 200uJ per
pulse. RESULTS: Subretinal fluid (SRF) was completely resolved in 74% (37/50
eyes) at month 3. Mean BCVA (LogMAR) was improved from 0.44 +/- 0.29 at baseline
to 0.37 +/- 0.32 at month 3 (p = 0.001). MMT was decreased from 335.0 +/- 99.8
MUm at baseline to 236.4 +/- 66.4 MUm after 3 months (p < 0.001). SRF height was
decreased from 168.0 +/- 77.3 MUm at baseline to 29.0 +/- 57.3 MUm after 3 months
(p < 0.001). However, the changes in SCT were not statistically significant (p =
0.48). CONCLUSIONS: SRT treatment with RFD showed favorable visual and anatomical
outcomes in patients with chronic CSC.
PMID- 28421343
TI - Antiplatelets and anticoagulants in vitreoretinal surgery, with a special
emphasis on novel anticoagulants: a national survey and review.
AB - PURPOSE: To survey current practice and opinion regarding the cessation of
antiplatelet and anticoagulant agents prior to vitreoretinal surgery, with
special emphasis on novel anticoagulants, and to provide an overview of current
literature. METHODS: An online survey was sent to 167 members of the British and
Eire Association of Vitreoretinal Surgeons (BEAVRS). A literature search and
analysis was conducted on studies that reviewed the bleeding risk of antiplatelet
and anticoagulant agents. RESULTS: The majority (93% for aspirin, 82% for
clopidogrel) of respondents would not suspend antiplatelet administration, and
79% would not stop warfarin before vitreoretinal surgery. Regarding the novel
anticoagulants (factor Xa inhibitors), 58% would not stop them, and 24% were
unsure. Eighty-three percent of the surgeons were not confident regarding the
management of factor Xa inhibitors preoperatively. Thirty-one percent of the
respondents felt that anticoagulation cessation was independent of the type of
vitreoretinal surgery, whereas 9% each felt that they would stop anticoagulation
if possible for diabetic vitrectomy and retinectomy. Published evidence suggests
that antiplatelet agents and warfarin do not confer a significantly greater risk
of intra- or perioperative bleeding. Evidence regarding the novel anticoagulants
is sparse. CONCLUSIONS: Further evaluation of novel anticoagulants in
vitreoretinal surgery is required in order to provide evidence-based
recommendations and address variations in practice.
PMID- 28421344
TI - Subacute cutaneous lupus erythematosus - paraneoplastic to gastric
adenocarcinoma?
PMID- 28421346
TI - Decoupling of Behavioral Trait Correlation Across Life Stages in Two
Holometabolous Insects.
AB - Many animal behaviors have a genetic base, and behavioral traits often correlate
with one another. In this study, we tested for a behavioral correlation between
tonic immobility and walking distance in the larval and adult stages
independently of two holometabolous insects. We confirmed a negative correlation
of traits between strains in adults of both the species; however, we did not find
it in larvae of either species. This suggests that the negative correlation
between tonic immobility and walking is decoupled across life stages from larva
to adult. In contrast, previous studies have reported that phenotypic
correlations between behavioral traits are maintained from larvae to adults in
hemimetabolous insects. In addition, our present results differ from previous
results with holometabolous insects. Therefore, our results suggest that
metamorphosis can change trade-offs between behavioral traits.
PMID- 28421345
TI - Long-term predictors of anxiety and depression in adult patients with asthma.
AB - BACKGROUND: It is well established that anxiety and depression are associated
with asthma, but there is limited evidence about the persistence of
anxiety/depression in asthma. The aim of our study was to assess the long-term
predictors of anxiety and depression in adult asthmatic patients. METHODS: A
total of 90 adult asthma patients (63 women, age 18-50 years) with different
levels of disease control (28 uncontrolled and 34 partially controlled) were
assessed at baseline and at follow-up after 7 years for anxiety, depression and
asthma control. The same work-up on both occasions included: demographics, living
conditions, medical history (e.g. comorbidities, adherence and exacerbations),
Hospital Anxiety and Depression Scale (HADS), Asthma Quality of Life
Questionnaire (AQLQ), disease control and lung function. Persistence was defined
as the HADS scores for anxiety and depression present at baseline and follow-up.
RESULTS: The HADS results at follow-up visit showed 36 (40%) asthma patients with
anxiety and 13 (14%) with depression, with the persistence of anxiety in 17 (19%)
and of depression in 7 (8%) patients. Significant predictors of anxiety at follow
up were HADS and AQLQ results at baseline and several parameters of asthma
control at follow-up (area under the curve AUC 0.917, 95% confidence interval CI
0.829-0.969, p < 0.001) and for depression AQLQ mood disorder domain, asthma
control and lung function (AUC 0.947, 95% CI 0.870-0.986, p < 0.001). CONCLUSION:
Anxiety and depression persist over years in some patients with asthma. The
association between mood disorders and asthma suggests potential mutual
treatability.
PMID- 28421347
TI - TU-100 exerts a protective effect against bacterial translocation by maintaining
the tight junction.
AB - PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride
(CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism
underlying this effect has not been fully elucidated. The aim of this study was
to further clarify the mechanism of CPT-11-induced bacterial translocation (BT)
and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro
by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3
groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the
CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats
were sacrificed on day 6 and their tissues were collected. RESULTS: CPT-11 and TU
100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11
treated rats developed different grades of diarrhea and BT was observed in 80% of
the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6,
TNF-alpha, IL-1beta and caspase-3 mRNAs in the large intestine. The expression of
tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was
significantly decreased in comparison to the control group. TU-100 co-treatment
significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-alpha,
IL-1beta and caspase-3, and improved the expression of occludin, claudin-4 and ZO
1. CONCLUSIONS: TU-100 can suppress the adverse effects associated with CPT-11
and improve the function of the TJ. It is possible that this occurs through the
TLR pathway.
PMID- 28421348
TI - The basal nutritional state of PDAC patients is the dominant factor for
completing adjuvant chemotherapy.
AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and several
clinical trials have shown that adjuvant chemotherapy after curative resection
can improve the prognosis of these patients. However, the adjuvant chemotherapy
completion rate is less than satisfactory. If this rate could be increased then
the overall prognosis of PDAC might be improved; however, reports addressing this
problem are insufficient. To elucidate the factors, we retrospectively
investigated PDAC patients. METHODS: Various factors of 121 PDAC patients
undergoing R0 resection, including preoperatively treated patients, were
investigated. Univariate and multivariate analyses were performed to investigate
the factors that were associated with the completion of adjuvant chemotherapy.
RESULTS: The analysis identified age and the prognostic nutritional index (PNI)
as significant independent factors. A receiver operating characteristic curve
analysis of age yielded a cutoff value of 67 years (sensitivity, 64%;
specificity, 78%). Univariate and multivariate analyses of the 61 patients who
were over 67 years of age revealed that the PNI (odds ratio, 0.85; P = 0.048) and
Evans grade (odds ratio, 0.041; P = 0.0010) were significant factors for the
completion of chemotherapy. CONCLUSIONS: The results of our investigation suggest
that nutrition should be controlled in older PDAC patients to facilitate the
completion of adjuvant chemotherapy.
PMID- 28421349
TI - Predictive detection areas for identifying additional MRI-detected breast lesions
on second-look ultrasonography.
AB - PURPOSE: Identifying an additional MRI-detected breast lesion on second-look
ultrasonography (US) is technically challenging because of lesion displacement
with the patient's position change. The aim of this study is to help identify MRI
detected lesions on second-look US by developing a probing area, called "the
predictive detection area" (PDA), and by assessing the PDA. METHODS: We measured
the nipple-to-lesion distances (NLDs) for 16 breast lesions on prone- and supine
position MRI sets and calculated the difference and angle between the two NLD
vectors, representing the lesion displacement. The minimum and maximum
differences and angles were chosen to form the PDA. Another 22 breast lesions,
detected in the prone MRI, were identified on US by probing the PDA to evaluate
the probability of existence. RESULTS: The width between the minimum and maximum
differences in two NLDs and the angle to form the PDA for the upper-inner, upper
outer, and lower-outer quadrants were 23.0 mm and 95.0 degrees , 29.0 mm and 41.0
degrees , and 18.0 mm and 17.0 degrees , respectively. The respective
probabilities of existence were 100, 80, and 100%. CONCLUSIONS: The PDA had a
high probability of existence and was acceptably accurate; therefore, the PDA in
a second-look US has the potential to help operators to quickly identify
additional MRI-detected lesions.
PMID- 28421350
TI - Preoperative imaging evaluation of pancreatic pathologies for the objective
prediction of pancreatic fistula after pancreaticoduodenectomy.
AB - In performing pancreaticoduodenectomy (PD) or when conducting clinical trials
involving PD procedure, a universal platform for predicting the risk of
postoperative pancreatic fistula (POPF) is indispensable. In this article, the
most significant imaging studies that focused on the objective preoperative
assessment of pancreatic pathologies in association with the occurrence of POPF
after PD were reviewed. Several recently developed imaging modalities can
objectively predict the occurrence of POPF after PD by assessing the elasticity,
fibrosis, and fatty infiltration of the pancreas. These valuable imaging
modalities include: (1) acoustic radiation force impulse ultrasound (US)
electrography which provides information about the elastic properties of the
pancreas; (2) contrast-enhanced computed tomography (CT) and magnetic resonance
imaging (MRI) with/without contrast-enhancement which reflect the histological
degree of pancreatic fibrosis; and (3) multi-detector row CT and/or MRI which
reflects the microscopic fatty infiltration of the pancreas. The precise and
objective preoperative risk assessment of POPF enables surgeons to customize
appropriate management strategies for individual patients undergoing PD. This
would be also beneficial for stratifying patients for enrolment in relevant
studies that involve pancreatic head resection, as objective criteria could be
set for the definitive evaluation of collected data related to surgical outcomes
across different institutions and surgeons.
PMID- 28421351
TI - Characteristics and prognosis of rectal gastrointestinal stromal tumors: an
analysis of registry data.
AB - PURPOSE: Rectal gastrointestinal stromal tumors (GISTs) are rare. Accordingly,
their clinical features are not well-documented and optimal treatment has not
been established. The objective of this study is to clarify the rates and
patterns of recurrence after surgical resection of rectal GISTs, with a focus on
outcomes and therapeutic modalities. METHODS: The registry was designed to
collect data on rectal GISTs recorded between January, 2003 and December, 2007 at
40 participating institutions of the Kinki GIST Study Group. The principal
variables were the rates and patterns of recurrence of rectal GISTs. Other study
variables were age, sex, tumor size, mitotic count, distance from the anal verge,
tumor location, surgical procedures, surgical margins, and recurrence-free
survival. RESULTS: Twenty-four cases were registered, 11 (45.8%) of which were
classified as high-risk by the modified NIH criteria. Locoregional recurrence
(7/23, 30.4%) was the predominant recurrence pattern after curative resection,
with rates that did not differ after local excision (33.3%; 3/9) vs. extended
resection (28.6%; 4/14). The recurrence rates were high (25.0%) even for patients
with low-risk disease. There was only one case of recurrence among patients who
received perioperative treatment with imatinib. CONCLUSIONS: Rectal GISTs showed
high rates of local recurrence regardless of the surgical procedure.
Perioperative treatment with imatinib may improve outcomes.
PMID- 28421352
TI - A New Role of Fine Excipient Materials in Carrier-Based Dry Powder Inhalation
Mixtures: Effect on Deagglomeration of Drug Particles During Mixing Revealed.
AB - The potential of fine excipient materials to improve the performance of carrier
based dry powder inhalation mixtures is well acknowledged. The mechanisms
underlying this potential are, however, open to question till date. Elaborate
understanding of these mechanisms is a requisite for rational rather than
empirical development of ternary dry powder inhalation mixtures. While effects of
fine excipient materials on drug adhesion to and detachment from surfaces of
carrier particle have been extensively investigated, effects on other processes,
such as carrier-drug mixing, capsule/blister/device filling, or aerosolization in
inhaler devices, have received little attention. We investigated the influence of
fine excipient materials on the outcome of the carrier-drug mixing process. We
studied the dispersibility of micronized fluticasone propionate particles after
mixing with alpha-lactose monohydrate blends comprising different fine particle
concentrations. Increasing the fine (D < 10.0 MUm) excipient fraction from 1.84
to 8.70% v/v increased the respirable drug fraction in the excipient-drug mixture
from 56.42 to 67.80% v/v (p < 0.05). The results suggest that low concentrations
of fine excipient particles bind to active sites on and fill deep crevices in
coarse carrier particles. As the concentration of fine excipient particles
increases beyond that saturating active sites, they fill the spaces between and
adhere to the surfaces of coarse carrier particles, creating projections and
micropores. They thereby promote deagglomeration of drug particles during carrier
drug mixing. The findings pave the way for a comprehensive understanding of
contributions of fine excipient materials to the performance of carrier-based dry
powder inhalation mixtures.
PMID- 28421353
TI - Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Infected
Young Russian Women: Comparison to Self-Report Assessments of Alcohol Use.
AB - Alcohol use is particularly deleterious for HIV-infected individuals and thus
accurate assessment of alcohol consumption is crucial in this population.
Phosphatidylethanol (PEth) provides an objective assessment of drinking and can
be compared to self-reported alcohol assessments to detect underreporting. The
purpose of this study was to identify underreporting and its potential predictors
in an HIV-infected sample of young Russian women. The current study examined the
concordance between a quantitative measure of PEth and self-reported recent
alcohol consumption in a prospective sample of HIV-infected young women (N = 204)
receiving medical care in Saint Petersburg, Russia. At baseline, 53% of
participants who denied drinking in the prior 30 days tested positive for PEth
(i.e., underreporters), although this rate decreased significantly at a three
month follow-up assessment. Further exploration did not identify consistent
predictors of underreporting status. Quantitative PEth levels showed, at best,
modest overlap to self-reported alcohol consumption among those reporting alcohol
use (e.g., Spearman's r = 0.27 between PEth and total drinks past-30 days at
baseline). Objective measures of alcohol consumption demonstrate modest overlap
with self-report measures of use in HIV-infected young Russian women.
Incorporating objective and quantifiable biological markers are essential for
valid assessments of alcohol use.
PMID- 28421355
TI - Addressing Early Retention in Antenatal Care Among HIV-Positive Women Through a
Simple Intervention in Kinshasa, DRC: The Elombe "Champion" Standard Operating
Procedure.
AB - This cluster-randomized study aimed to assess the Elombe ("Champion") standard
operating procedure (SOP), implemented by providers and Mentor Mothers, on HIV
positive pregnant women's retention between first and second antenatal visits.
Sixteen facilities in Kinshasa were randomly assigned to intervention (SOP) or
comparison (no SOP). Effect of the SOP was estimated using relative risk. Women
in comparison facilities were more likely to miss second visits (RR 2.5, 95% CI
1.05-5.98) than women in intervention facilities (30.0%, n = 27 vs. 12.0%, n = 9,
p < 0.002). Findings demonstrate that a simple intervention can reduce critical
early loss to care in PMTCT programs providing universal, lifelong treatment.
PMID- 28421354
TI - Perceived Barriers and Facilitators to Integrating HIV Prevention and Treatment
with Cross-Sex Hormone Therapy for Transgender Women in Lima, Peru.
AB - Transgender women (TW) represent a vulnerable population at increased risk for
HIV infection in Peru. A mixed-methods study with 48 TW and 19 healthcare
professionals was conducted between January and February 2015 to explore barriers
and facilitators to implementing a model of care that integrates HIV services
with gender-affirmative medical care (i.e., hormone therapy) in Lima, Peru.
Perceived acceptability of the integrated care model was high among TW and
healthcare professionals alike. Barriers included stigma, lack of provider
training or Peruvian guidelines regarding optimal TW care, and service delivery
obstacles (e.g., legal documents, spatial placement of clinics, hours of
operation). The hiring of TW staff was identified as a key facilitator for
engagement in health care. Working in partnership with local TW and healthcare
provider organizations is critical to overcoming existing barriers to successful
implementation of an integrated HIV services and gender-affirmative medical care
model for this key population in Peru.
PMID- 28421356
TI - The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel
Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in
Resource-Limited Settings.
AB - Although mobile health (mHealth) technologies have shown promise in improving
clinical care in resource-limited settings (RLS), they are infrequently brought
to scale. One limitation to the success of many mHealth interventions is
inattention to end-user acceptability, which is an important predictor of
technology adoption. We conducted in-depth interviews with 43 people living with
HIV in rural Uganda who had participated in a clinical trial of a short messaging
system (SMS)-based intervention designed to prompt return to clinic after an
abnormal laboratory test. Interviews focused on established features of
technology acceptance models, including perceived ease of use and perceived
usefulness, and included open-ended questions to gain insight into unexplored
issues related to the intervention's acceptability. We used conventional
(inductive) and direct content analysis to derive categories describing use
behaviors and acceptability. Interviews guided development of a proposed
conceptual framework, the technology acceptance model for resource-limited
settings (TAM-RLS). This framework incorporates both classic technology
acceptance model categories as well as novel factors affecting use in this
setting. Participants described how SMS message language, phone characteristics,
and experience with similar technologies contributed to the system's ease of use.
Perceived usefulness was shaped by the perception that the system led to
augmented HIV care services and improved access to social support from family and
colleagues. Emergent themes specifically related to mHealth acceptance among PLWH
in Uganda included (1) the importance of confidentiality, disclosure, and stigma,
and (2) the barriers and facilitators downstream from the intervention that
impacted achievement of the system's target outcome. The TAM-RLS is a proposed
model of mHealth technology acceptance based upon end-user experiences in rural
Uganda. Although the proposed model requires validation, the TAM-RLS may serve as
a useful tool to guide design and implementation of mHealth interventions.
PMID- 28421357
TI - Incidence of autoimmune diseases in patients with scabies: a nationwide
population-based study in Taiwan.
AB - Scabies is a commonly occurring infectious immune-mediated inflammatory skin
disease. Immune-mediated inflammatory processes are also observed in autoimmune
diseases. There have been very few previous studies; however, that have
investigated the possible association between scabies and autoimmune diseases. To
address this research gap, we conducted a nationwide population-based cohort
study that included a total of 4481 scabies patients and 16,559 control subjects
matched by gender, age, insured region, urbanization and income. We tracked both
cohorts for a 7-year period to identify the incidence of autoimmune diseases in
both groups during that follow-up period. Relatedly, a Cox regression analysis
was performed to calculate and compare the hazard ratio (HR) for autoimmune
diseases of both groups. An overall increased risk for 19 autoimmune diseases was
observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04
1.25). Compared with the control group, the scabies patients exhibited increased
risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64-18.07),
dermatomyositis (aHR 4.91, 95% CI 1.80-13.38), polyarteritis nodosa (aHR 2.89,
95% CI 1.46-5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33-5.64),
psoriasis (aHR 2.31, 95% CI 1.85-2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31
3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53-2.44), pernicious anemia
(aHR 1.92, 95% CI 1.42-2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12
1.83). In conclusion, the associations between scabies and a variety of
autoimmune diseases may exist. Further studies are needed to clarify the shared
etiologies and relationships between scabies and autoimmune diseases.
PMID- 28421358
TI - Vitamin D supplementation for the management of knee osteoarthritis: a systematic
review of randomized controlled trials.
AB - Conflicting evidence exists concerning the supplementation of vitamin D in knee
osteoarthritis condition. This systematic literature review was done to explore
the effects of vitamin D supplementation in the management of knee
osteoarthritis. Electronic literature search was done in databases like
PubMed(r), Embase(r), and Cochrane CENTRAL from inception to 6th July 2016. The
quality of included Randomized Controlled Trials (RCTs) was assessed using
Cochrane risk of bias tool. We considered change in Western Ontario and McMaster
Universities (WOMAC) index, Visual Analog Scale (VAS) and Functional Pain Score
(FPS) as the primary outcome measure. Change in tibial cartilage thickness, joint
space width and safety profile was considered as secondary outcomes. Participants
were randomized either to treatment or placebo group. Participants received
cholecalciferol as an intervention through oral route in the dose range of 800
60,000 IU except in the one study where participants received ergocalciferol. All
included RCTs showed a significant increase in serum vitamin D level in the
treatment group compared to the placebo group at the end point. No significant
reduction in pain and function was reported on WOMAC scale except in one study.
No significant difference was reported for WOMAC stiffness in any study. VAS was
assessed in three studies in which two showed statistically significant
improvement in knee pain. Three of the RCTs reported safety data with one
incidence of calculus ureteric and hip fracture found to be related to the drug.
The study found evidence from RCTs to be insufficient to support the use of
vitamin D supplementation for patients with knee osteoarthritis.
PMID- 28421359
TI - The theory of planned behaviour explains intentions to use antiresorptive
medication after a fragility fracture.
AB - Our objective was to ascertain whether the Theory of Planned Behaviour (TPB)
explains patient intentions to use antiresorptive medication after a fracture. A
qualitative study was conducted with English-speaking members of the Canadian
Osteoporosis Patient Network (COPN) who had sustained a fragility fracture at 50+
years of age and were not taking antiresorptive medication at the time of that
fracture. Questions during a 1-h telephone interview were guided by the domains
of the TPB: they addressed the antecedent constructs regarding antiresorptive
medication (attitudes, subjective norms, and perceived behavioural control) as
well as intentions regarding antiresorptive medication use. We created a coding
template a priori based on the TPB domains and applied this template to the
interview data. Twenty-six eligible participants (24 females, 2 males) aged 51-89
completed an interview. The TPB appeared to be predictive of intentions in 19
(73%) participants. In the majority of participants where the TPB did not appear
to be predictive (57%), a positive attitude toward antiresorptive medication was
the most important antecedent variable in determining intentions. The TPB
appeared to be predictive of intentions to use antiresorptive medication among
individuals who had experienced a fragility fracture. Attitudes towards
medication were especially important.
PMID- 28421360
TI - Update on Chemotherapy-Induced Peripheral Neuropathy.
AB - PURPOSE OF REVIEW: The purpose of this study was to briefly discuss chemotherapy
induced peripheral neuropathy (CIPN) and detail the most important and most
recent chemotherapeutic agents implicated. This review will examine neuropathy
mechanisms, risk factors, and clinical patterns; novel and prospective drugs with
similar effects that are less well known to neurologists are discussed. RECENT
FINDINGS: CIPN is increasingly recognized for its clinical importance and effect
on patient quality of life. Identification of risk factors is ongoing and may
enable future risk stratification. Newer classes of agents and new members of
existing classes are continually recognized, notably immune check point
inhibitors, other monoclonal antibody treatments, novel immunomodulatory agents,
and proteasome inhibitors. Advances regarding established classes including
taxanes, platins, and vinca alkaloids are also reviewed. CIPN is an important
often dose-limiting toxicity. Multiple agents cause neuropathy; various clinical
patterns are described. Future studies should aim at improved understanding of
toxicity mechanisms and development of preventive and therapeutic strategies.
PMID- 28421361
TI - Erratum to: A comparative study of the bone contact to zirconium and titanium
implants after 8 weeks of implantation in rabbit femoral condyles.
PMID- 28421362
TI - Selective Imaging of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2
in Atherosclerotic Lesions in Diabetic and Non-diabetic ApoE-/- Mice.
AB - PURPOSE: Plaque vulnerability is associated with inflammation and angiogenesis,
processes that rely on vascular endothelial growth factor (VEGF) signaling via
two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced
uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed
tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies
accelerated atherosclerosis in diabetic relative to non-diabetic ApoE-/- mice.
Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we
reasoned that selective imaging of each receptor can provide more detailed
information on plaque biology. PROCEDURES: Recently described VEGFR-1 and VEGFR-2
selective mutants of scVEGF, named scVR1 and scVR2, were site-specifically
derivatized with Tc-99m chelator DOTA via 3.4 kDa PEG linker, and their
selectivity to the cognate receptors was confirmed in vitro. scVR1 and scVR2
conjugates were radiolabeled with Tc-99m to specific activity of 110 +/- 11
MBq/nmol, yielding tracers named scVR1/Tc and scVR2/Tc. 34-40 week old diabetic
and age-matched non-diabetic ApoE-/- mice were injected with tracers, 2-3 h later
injected with x-ray computed tomography (CT) contrast agent and underwent hybrid
SPECT/CT imaging. Tracer uptake, localized to proximal aorta and brachiocephalic
vessels, was quantified as %ID from. Tracer uptake was also quantified as %ID/g
from gamma counting of harvested plaques. Harvested atherosclerotic arterial
tissue was used for immunofluorescent analyses of VEGFR-1 and VEGFR-2 and various
lineage-specific markers. RESULTS: Focal, receptor-mediated uptake in proximal
aorta and brachiocephalic vessels was detected for both scVR1/Tc and scVR2/Tc
tracers. Uptake of scVR1/Tc and scVR2/Tc was efficiently inhibited only by "cold"
proteins of the same receptor selectivity. Tracer uptake in this area, expressed
as %ID, was higher in diabetic vs. non- diabetic mice for scVR1/Tc (p = 0.01) but
not for scVR2/Tc. Immunofluorescent analysis revealed enhanced VEGFR-1 prevalence
in and around plaque area in diabetic mice. CONCLUSIONS: Selective VEGFR-1 and
VEGFR-2 imaging of atherosclerotic lesions may be useful to explore plaque
biology and identify vulnerability.
PMID- 28421363
TI - Response to Dr. Hawkes letter regarding HPV vaccine serious adverse events.
PMID- 28421364
TI - An ovine in vivo framework for tracheobronchial stent analysis.
AB - Tracheobronchial stents are most commonly used to restore patency to airways
stenosed by tumour growth. Currently all tracheobronchial stents are associated
with complications such as stent migration, granulation tissue formation, mucous
plugging and stent strut fracture. The present work develops a computational
framework to evaluate tracheobronchial stent designs in vivo. Pressurised
computed tomography is used to create a biomechanical lung model which takes into
account the in vivo stress state, global lung deformation and local loading from
pressure variation. Stent interaction with the airway is then evaluated for a
number of loading conditions including normal breathing, coughing and
ventilation. Results of the analysis indicate that three of the major
complications associated with tracheobronchial stents can potentially be analysed
with this framework, which can be readily applied to the human case. Airway
deformation caused by lung motion is shown to have a significant effect on stent
mechanical performance, including implications for stent migration, granulation
formation and stent fracture.
PMID- 28421365
TI - Grass carp reovirus outer capsid proteins VP5 and VP7 interact in vitro.
AB - Grass carp reovirus (GCRV) causes viral hemorrhagic disease in cultured grass
carp. However, there is no effective means of controlling GCRV. Previous studies
have shown, by cryoelectron microscopy, that the outer capsid of GCRV is composed
of 200 trimers of VP5-VP7 heterodimers. However, confirmation of this interaction
between VP5 and VP7 through molecular biochemistry is still lacking. This study
characterized the interactions between VP5 and VP7 in vitro. VP5 was shown to
interact with VP7 in a commercial yeast-two-hybrid screen. A dot-blot overlay
assay was used to show that VP7 binding to VP5 was dose-dependent. Finally, a
yeast-two-hybrid approach confirmed interactions between full-length and
truncated forms of VP5 and VP7. In conclusion, our results indicate that VP5 and
VP7 interact directly in vitro.
PMID- 28421366
TI - Two deletion variants of Middle East respiratory syndrome coronavirus found in a
patient with characteristic symptoms.
AB - Significant sequence variation of Middle East respiratory syndrome coronavirus
(MERS CoV) has never been detected since it was first reported in 2012. A MERS
patient came from Korea to China in late May 2015. The patient was 44 years old
and had symptoms including high fever, dry cough with a little phlegm, and
shortness of breath, which are roughly consistent with those associated with
MERS, and had had close contact with individuals with confirmed cases of
MERS.After one month of therapy with antiviral, anti-infection, and immune
enhancing agents, the patient recovered in the hospital and was discharged. A
nasopharyngeal swab sample was collected for direct sequencing, which revealed
two deletion variants of MERS CoV. Deletions of 414 and 419 nt occurred between
ORF5 and the E protein, resulting in a partial protein fusion or truncation of
ORF5 and the E protein. Functional analysis by bioinformatics and comparison to
previous studies implied that the two variants might be defective in their
ability to package MERS CoV. However, the mechanism of how these deletions
occurred and what effects they have need to be further investigated.
PMID- 28421367
TI - NS3 protease resistance-associated substitutions in liver tissue and plasma
samples from patients infected by hepatitis C virus genotype 1A or 1B.
AB - The presence of naturally occurring resistance-associated substitutions (RASs) in
the HCV-protease domain has been poorly investigated in the liver, the main site
of HCV replication. We evaluated the natural resistance of the virus to NS3
protease inhibitors in liver tissue and plasma samples taken from HCV-infected
patients. RASs were investigated by means of viral population sequencing in liver
tissue samples from 18 HCV-infected patients harbouring genotype 1a or genotype
1b; plasma samples from 12 of these patients were also available for virological
investigation. A discordant genotype was found in two of the 12 patients (16.6%)
who provided samples from both compartments. Sequence analysis of the NS3
protease domain showed the presence of RASs in four of the 18 liver tissue
samples (22.2%), two of which showed cross-resistance to protease inhibitors in
clinical use or phase 2-3 trials. The analysis of the 12 paired tissues and
plasma samples excluded the presence of RASs in the plasma compartment. The
dominance of discordant genotypes in the paired liver and plasma samples of some
HCV-infected patients suggests mixed infection possibly leading to the selective
advantage of different genotype in the two compartments. The presence of RASs at
intra-hepatic level is not uncommon and may lead to the early emergence of cross
resistant strains.
PMID- 28421368
TI - Recombinant foot-and-mouth disease virus (FMDV) non-structural protein 3A fused
to enhanced green fluorescent protein (EGFP) as a candidate probe to identify
FMDV-infected cattle in serosurveys.
AB - Recombinant protein 3A-EGFP, a fusion construct between foot-and-mouth disease
virus (FMDV) non-structural protein 3A and the enhanced green fluorescent protein
(EGFP) was expressed in BL21-DE3 cells. The identity of the partially purified
protein 3A-EGFP was confirmed by its reactivity with sera from cattle infected
with FMDV and with a monoclonal antibody specific for FMDV-3ABC (MAb3H7) in
Western blot assays. No reactivity was observed with sera from uninfected
vaccinated animals. The performance of 3A-EGFP as an antigen in an indirect
enzyme-linked immunosorbent assay (ELISA) was assessed and compared with that of
a previously developed and validated capture ELISA that uses a 3ABC recombinant
antigen (3ABC ELISA) and has been widely applied for serological surveys in
Argentina. Parallel analysis of strongly and weakly positive reference sera from
infected animals and 329 serum samples from uninfected vaccinated cattle showed
that the 3A-EGFP antigen unequivocally identifies sera from FMDV-infected cattle
with similar performance to its 3ABC counterpart. The 3A-EGFP ELISA is simpler
and faster to perform than the 3ABC ELISA, since it does not require a capture
step with a specific antibody. Moreover, the expression and storage of the
recombinant 3A-EGFP is simplified by the absence of residual autoproteolytic
activity associated to the 3C sequence. We conclude that the 3A-EGFP ELISA
constitutes a promising screening method in serosurveys to determine whether or
not animals are infected with FMDV.
PMID- 28421369
TI - Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid
tissue lymphoma from benign lymphoproliferative tumors.
AB - PURPOSE: To evaluate novel immunophenotypic profiles of patients with orbital
lymphoproliferative tumors. METHODS: From 2006 to 2014, surgical biopsies from
consecutive patients with newly diagnosed orbital mucosa-associated lymphoid
tissue (MALT) lymphoma and IgG4-related ophthalmic disease (IgG4-ROD) were
collected from Tokyo Medical University Hospital. A total of 44 tumors from 44
patients were analyzed, including 21 with orbital MALT lymphoma (11 men and 10
women, mean age 67.8 +/- 13.4 years) and 23 with definitive IgG4-ROD (9 men and
14 women, mean age 60.5 +/- 15.1 years). Patients with secondary orbital MALT
lymphoma and MALT lymphoma with IgG4-ROD were excluded. All patients were
immunocompetent Asian adults. Samples were analyzed by immunohistochemistry and
flow cytometric analysis. Flow cytometry was performed with the following
antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, CD25, CD30, CD34, and
CD56 lambda and kappa chains. RESULTS: Expression of CD25 and CD19 was higher in
patients with orbital MALT lymphoma compared to patients with IgG4-ROD (p <
0.001). In contrast, expression of CD3, CD4, and CD23 was higher in patients with
orbital IgG4-ROD compared to those with MALT lymphoma (all p < 0.01). The
presence of CD23 and CD25 in the specimens was confirmed by immunohistochemistry.
CONCLUSION: The present study elucidated the novel immunophenotypic features of
orbital MALT and benign lymphoproliferative disorders such as IgG4-ROD. Among
them, CD23 and CD25 have shown a disease-specific expression pattern.
PMID- 28421371
TI - Temperature-dependent signal transmission in chloroplast accumulation response.
AB - Chloroplast photorelocation movement, well-characterized light-induced response
found in various plant species from alga to higher plants, is an important
phenomenon for plants to increase photosynthesis efficiency and avoid
photodamage. The signal for chloroplast accumulation movement connecting the blue
light receptor, phototropin, and chloroplasts remains to be identified, although
the photoreceptors and the mechanism of movement via chloroplast actin filaments
have now been revealed in land plants. The characteristics of the signal have
been found; the speed of signal transfer is about 1 um min-1 and that the signal
for the accumulation response has a longer life and is transferred a longer
distance than that of the avoidance response. Here, to collect the clues of the
unknown signal substances, we studied the effect of temperature on the speed of
signal transmission using the fern Adiantum capillus-veneris and found the
possibility that the mechanism of signal transfer was not dependent on the simple
diffusion of a substance; thus, some chemical reaction must also be involved. We
also found new insights of signaling substances, such that microtubules are not
involved in the signal transmission, and that the signal could even be
transmitted through the narrow space between chloroplasts and the plasma
membrane.
PMID- 28421370
TI - The current state of knowledge on the neuroactive compounds that affect the
development, mating and reproduction of spiders (Araneae) compared to insects.
AB - The neuroendocrine system of insects, including the presence of the main
neuroactive compounds, and their role in ontogenesis are probably best understood
of all the arthropods. Development, metamorphosis, the maturation of the gonads,
vitellogenesis and egg production are regulated by hormones (juvenile hormones,
ecdysteroids) and neuropeptides. However, knowledge about their presence and
functions in spiders is fragmentary. In this paper, we present a summary of the
current data about the juvenile hormones, ecdysteroids and neuropeptides in
selected groups of arthropods, with particular emphasis on spiders. This is the
first article that takes into account the occurrence, action and role of hormones
and neuropeptides in spiders. In addition, the suggestions for possible ways to
study these compounds in Araneomorphae spiders are unique and cannot be found in
the arachnological literature.
PMID- 28421372
TI - Vascular development of the grapevine (Vitis vinifera L.) inflorescence rachis in
response to flower number, plant growth regulators and defoliation.
AB - The grapevine inflorescence is a determinate panicle and as buds emerge, shoot,
flower and rachis development occur simultaneously. The growth and architecture
of the rachis is determined by genetic and environmental factors but here we
examined the role of flower and leaf number as well as hormones on its elongation
and vascular development. The consequences of rachis morphology and vascular area
on berry size and composition were also assessed. One week prior to anthesis,
Merlot and Cabernet Sauvignon field vines were exposed to manual flower removal,
exogenous plant growth regulators or pre-bloom leaf removal. Manual removal of
half the flowers along the vertical axis of the inflorescence resulted in a
shorter rachis in both cultivars. Conversely, inflorescences treated with
gibberellic acid (GA3) and the synthetic cytokinin, 6-benzylaminopurine (BAP)
resulted in a longer rachis while pre-bloom removal of all leaves on the
inflorescence-bearing shoot did not alter rachis length relative to untreated
inflorescences. Across the treatments, the cross-sectional areas of the
conducting xylem and phloem in the rachis were positively correlated to rachis
girth, flower number at anthesis, bunch berry number, bunch berry fresh mass and
bunch sugar content at harvest. Conversely, average berry size and sugar content
were not linked to rachis vascular area. These data indicate that the
morphological and vascular development of the rachis was more responsive to
flower number and plant growth regulators than to leaf removal.
PMID- 28421373
TI - Role of glycogen synthase kinase following myocardial infarction and ischemia
reperfusion.
AB - Glycogen synthase kinase-3 beta (GSK3beta) is principally is a glycogen synthase
phosphorylating enzyme that is well known for its role in muscle metabolism.
GSK3beta is a serine/threonine protein Kinase, which is responsible for several
essential roles in mammalian cells. This enzyme is implicated in the
pathophysiology of many conditions involved in homeostasis and cellular
immigration. GSK3beta is involved in several pathways leading to
neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
Increasing evidence has shown the potential importance of GSK3beta in ischemic
heart disease and ischemia-reperfusion pathologies. Reperfusion injury may occur
in tissues after prolonged ischemia following reperfusion. Reperfusion injury can
be life threatening. Reperfusion injury occurs due to a change in ionic
homeostasis, excess free radical production, mitochondrial damage and cell death.
There are however clear, cardiac-protective signals; although the molecular
pathophysiology is not clearly understood. In normal physiology, GSK3beta has a
critical role in the cytoprotective pathway. However, it's controversial role in
ischemia and ischemia-reperfusion is a topic of current interest. In this review,
we have opted to focus on GSK3beta interactions with mitochondria in ischemic
heart disease and expand on the therapeutic interventions.
PMID- 28421374
TI - Level of physical activity, well-being, stress and self-rated health in persons
with migraine and co-existing tension-type headache and neck pain.
AB - BACKGROUND: The prevalence of migraine with co-existing tension-type headache and
neck pain is high in the general population. However, there is very little
literature on the characteristics of these combined conditions. The aim of this
study was to investigate a) the prevalence of migraine with co-existing tension
type headache and neck pain in a clinic-based sample, b) the level of physical
activity, psychological well-being, perceived stress and self-rated health in
persons with migraine and co-existing tension-type headache and neck pain
compared to healthy controls, c) the perceived ability of persons with migraine
and co-existing tension-type headache and neck pain to perform physical activity,
and d) which among the three conditions (migraine, tension-type headache or neck
pain) is rated as the most burdensome condition. METHODS: The study was conducted
at a tertiary referral specialised headache centre where questionnaires on
physical activity, psychological well-being, perceived stress and self-rated
health were completed by 148 persons with migraine and 100 healthy controls
matched by sex and average age. Semi-structured interviews were conducted to
assess characteristics of migraine, tension-type headache and neck pain. RESULTS:
Out of 148 persons with migraine, 100 (67%) suffered from co-existing tension
type headache and neck pain. Only 11% suffered from migraine only. Persons with
migraine and co-existing tension-type headache and neck pain had lower level of
physical activity and psychological well-being, higher level of perceived stress
and poorer self-rated health compared to healthy controls. They reported reduced
ability to perform physical activity owing to migraine (high degree), tension
type headache (moderate degree) and neck pain (low degree). The most burdensome
condition was migraine, followed by tension-type headache and neck pain.
CONCLUSIONS: Migraine with co-existing tension-type headache and neck pain was
highly prevalent in a clinic-based sample. Persons with migraine and co-existing
tension-type headache and neck pain may require more individually tailored
interventions to increase the level of physical activity, and to improve
psychological well-being, perceived stress and self-rated health.
PMID- 28421375
TI - Obstructive sleep apnea increases the risk of cardiac events after percutaneous
coronary intervention: a meta-analysis of prospective cohort studies.
AB - PURPOSE: Recent studies have shown an association between obstructive sleep apnea
(OSA) and coronary artery disease; however, the association between OSA and
cardiac outcomes in patients after percutaneous coronary intervention (PCI)
remains undetermined. METHODS: PubMed, EMBASE, and CENTRAL were searched from
inception to July 2016 for cohort studies that followed up with patients after
PCI, and evaluated their overnight sleep patterns within 1 month for major
adverse cardiac events (MACEs) as primary outcomes including cardiac death, non
fatal myocardial infarction (MI), and coronary revascularization and secondary
outcomes including re-admission for heart failure and stroke. Outcomes data were
pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the
I 2 statistics. The methodological quality of the studies was assessed using the
Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual
investigation of funnel plots. RESULTS: We identified seven pertinent studies
including 2465 patients from 178 related articles. OSA was associated with MACEs
(odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20-1.93, I 2 = 29%),
which included cardiac death (OR 2.05, 95% CI, 1.15-3.65, I 2 = 0%), non-fatal MI
(OR 1.59, 95% CI, 1.14-2.23, I 2 = 15%), and coronary revascularization (OR 1.69,
95% CI, 1.28-2.23, I 2 = 0%). However, OSA was not associated with re-admission
for heart failure (OR 1.71, 95% CI, 0.99-2.96, I 2 = 0%) and/or stroke (OR 1.68,
95% CI, 0.91-3.11, I 2 = 0%) according to the pooled results. CONCLUSIONS: In
patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal
MI, and coronary revascularization.
PMID- 28421376
TI - Using the STOPBANG questionnaire and other pre-test probability tools to predict
OSA in younger, thinner patients referred to a sleep medicine clinic.
AB - BACKGROUND: The STOPBANG questionnaire is used to predict the presence of
obstructive sleep apnea (OSA). We sought to assess the performance of the
STOPBANG questionnaire in younger, thinner patients referred to a sleep medicine
clinic. METHODS: We applied the STOPBANG questionnaire to patients referred for
level I polysomnography (PSG) at our sleep center. We calculated likelihood
ratios and area under the receiver operator characteristic (AUROC) curve and
performed sensitivity analyses. RESULTS: We performed our analysis on 338
patients referred for PSG. Only 17.2% (n = 58) were above age 50 years, and 30.5
and 6.8% had a BMI above 30 and 35 years, respectively. The mean apnea-hypopnea
index (AHI) was 12.9 +/- 16.4 and 63.9% had an AHI >=5. The STOPBANG (threshold
>=3) identified 83.1% of patients as high risk for an AHI >=5, and sensitivity,
specificity, positive (PPV), and negative predictive values (NPV) were 83.8,
18.0, 64.4, and 38.0%, respectively. Positive and negative likelihood ratios were
poor at 1.02-1.11 and 0.55-0.90, respectively, across AHI thresholds (AHI >=5,
AHI >=15 and AHI >=30), and AUROCs were 0.52 (AHI >=5) and 0.56 (AHI >=15).
Sensitivity analyses adjusting for insomnia, combat deployment, traumatic brain
injury, post-traumatic stress disorder, clinically significant OSA (ESS >10
and/or co-morbid disease), and obesity did not significantly alter STOPBANG
performance. CONCLUSIONS: In a younger, thinner population with predominantly
mild-to-moderate OSA, the STOPBANG Score does not accurately predict the presence
of obstructive sleep apnea.
PMID- 28421377
TI - VEP and PERG in patients with multiple sclerosis, with and without a history of
optic neuritis.
AB - PURPOSE: Visual electrophysiology is routinely used to detect the visual
complications of multiple sclerosis, but the analysis mostly focuses on visual
evoked potential (VEP) and especially the P100 component. Our goal was to analyze
the components and waveform alterations of VEPs and pattern electroretinograms
(PERGs) in patients with multiple sclerosis (MS) with good vision. METHODS: The
main VEP and PERG components of 85 patients with MS were analyzed in two groups:
38 patients who had optic neuritis in their history (ON group) and 47 patients
who had never had optic neuritis (MS group). The results were compared against a
control group of 47 healthy subjects. RESULTS: Both VEP and PERG alterations
occurred in a greater number of patients than expected, and these alterations
were not necessarily linked to ON in the history or a deterioration of visual
acuity. CONCLUSIONS: Both VEP and PERG can detect dysfunction in the visual
system in MS, even if the patient has no subjective symptoms. Even if PERG is not
routinely used in neuro-ophthalmology, the results suggest that PERG assessment
may provide useful information describing the retinal defect in MS.
PMID- 28421379
TI - Role of taxanes in chemotherapy-related cognitive impairment: A prospective
longitudinal study.
AB - PURPOSE: The aim of this study is to elucidate the role of taxanes on cognition
when they are administered as a part of the treatment with a fluorouracil,
epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC). METHODS:
Two groups of women (n = 51) with a novel diagnostic of BC that were treated with
a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC
plus 8 cycles of taxanes) were compared at three moments: before chemotherapy,
after its completion (short-term evaluation) and at a mean of 74.5 weeks from
baseline as a long-term evaluation. RESULTS: Both groups showed worsening in
tests of attention and executive functions on the short-term assessment, with the
group treated with taxanes showing more number of affected cognitive measures at
this time point, including verbal learning and speed measures. At the long-term
evaluation, cognitive dysfunction was still found in attention and executive
functions in both groups. CONCLUSION: Our results suggest that chemotherapy for
BC with a FEC regimen can have a negative effect on cognition. Acute deficits
seem to be larger when taxanes are added, but treatment seems to affect cognition
also at long term.
PMID- 28421378
TI - Transcriptome-Based Identification of the Desiccation Response Genes in Marine
Red Algae Pyropia tenera (Rhodophyta) and Enhancement of Abiotic Stress Tolerance
by PtDRG2 in Chlamydomonas.
AB - Pyropia tenera (Kjellman) are marine red algae that grow in the intertidal zone
and lose more than 90% of water during hibernal low tides every day. In order to
identify the desiccation response gene (DRG) in P. tenera, we generated 1,444,210
transcriptome sequences using the 454-FLX platform from the gametophyte under
control and desiccation conditions. De novo assembly of the transcriptome reads
generated 13,170 contigs, covering about 12 Mbp. We selected 1160 differentially
expressed genes (DEGs) in response to desiccation stress based on reads per
kilobase per million reads (RPKM) expression values. As shown in green higher
plants, DEGs under desiccation are composed of two groups of genes for gene
regulation networks and functional proteins for carbohydrate metabolism, membrane
perturbation, compatible solutes, and specific proteins similar to higher plants.
DEGs that show no significant homology with known sequences in public databases
were selected as DRGs in P. tenera. PtDRG2 encodes a novel polypeptide of 159
amino acid residues locating chloroplast. When PtDRG2 was overexpressed in
Chlamydomonas, the PtDRG2 confer mannitol and salt tolerance in transgenic cells.
These results suggest that Pyropia may possess novel genes that differ from green
plants, although the desiccation tolerance mechanism in red algae is similar to
those of higher green plants. These transcriptome sequences will facilitate
future studies to understand the common processes and novel mechanisms involved
in desiccation stress tolerance in red algae.
PMID- 28421380
TI - Revisiting Mechanisms of Extraterritorial Allodynia.
PMID- 28421382
TI - Relationship Between the Expression of O6-Methylguanine-DNA Methyltransferase
(MGMT) and p53, and the Clinical Response in Metastatic Pancreatic Adenocarcinoma
Treated with FOLFIRINOX.
AB - BACKGROUND: To date, no predictive biomarker for the efficacy of FOLFIRINOX in
metastatic pancreatic adenocarcinoma has been demonstrated. Deficiency in O6
methylguanine-DNA methyltransferase (MGMT) has been associated with a therapeutic
response in endocrine tumors of the pancreas and the lack of expression of
protein 53 (p53) could interfere with the action of MGMT. OBJECTIVE: The aim of
our study was to assess the prevalence of MGMT and p53 in patients with
metastatic pancreatic adenocarcinoma treated with FOLFIRINOX as a first-line
treatment and to investigate their association with therapeutic response and
survival. PATIENTS AND METHODS: The immunohistochemical expression of MGMT was
recorded as present or absent and the expression of p53 was semi-quantitatively
scored in 30 patients with metastatic pancreatic adenocarcinoma, at Angers
Hospital in France between September 2011 and June 2015. Clinical and radiologic
data were collected retrospectively. RESULTS: The presence or absence of MGMT
expression entailed no significant differences in response rate. Median values of
progression-free survival (PFS) and overall survival (OS) were lower in patients
with MGMT expression, but sample size is too small to conclude that there is a
statistically significant difference. No significant relationship for response
rate and PFS was observed in relation with p53 expression. By contrast, patients
with a strong tumor expression of p53 had a significantly lower OS compared to
patients with no or weak expression of the protein (p = 0.027). There was a
positive correlation between the expression of p53 and MGMT (p = 0.08).
CONCLUSIONS: These preliminary findings suggest that for patients treated with
FOLFIRINOX as a first-line treatment for metastatic pancreatic adenocarcinoma,
the immunohistochemical evaluation of MGMT could not predict the clinical
outcome; however, the survival was not significant probably because of the under
powered study (due to small sample size). A strong tumor expression of p53 is
associated with a poor prognosis of OS.
PMID- 28421383
TI - Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of
Guanfacine Extended-Release Formulation in Healthy Japanese and Caucasian Male
Adults.
AB - BACKGROUND AND OBJECTIVE: Guanfacine extended-release (guanfacine XR) could be a
useful treatment option for children and adolescent patients with attention
deficit/hyperactivity disorder (ADHD). As an initial step in the development in
Japan, the pharmacokinetics, safety and tolerability were assessed in healthy
Japanese and non-Hispanic Caucasian adults. METHODS: A Phase 1, double-blind,
randomized, placebo-controlled, single- and multiple-oral dose escalation study
of guanfacine XR was conducted. Healthy Japanese and Caucasian subjects received
guanfacine XR 1 mg orally in the morning on Day 1. Following safety assessments,
subjects subsequently received guanfacine XR 1 mg (Days 4-8), 2 mg (Days 9-13), 3
mg (Days 14-18), and 4 mg (Days 19-23) once daily, followed by a taper-down
period. Single- and multiple-dose pharmacokinetic parameters were estimated based
on plasma concentration-time data and urine concentration data of guanfacine by
non-compartmental analysis. RESULTS: A total of 30 male subjects (15 Japanese and
15 Caucasian, active:placebo = 12:3) were enrolled. Of those receiving guanfacine
XR, 11/12 (91.7%) subjects in each active drug group completed the study.
Following multiple doses, the mean area under the plasma concentration-time
curves of guanfacine were 9-22% greater for Caucasian subjects than Japanese
subjects in the 1-3 mg dose range and 54% greater for the 4 mg. Guanfacine XR was
generally well tolerated by both ethnic groups, with most adverse events being
mild in both groups. There were no serious or severe adverse events during the
study and no adverse events led to withdrawal from the study. CONCLUSIONS:
Exposure to guanfacine in Japanese subjects tended to be lower than in Caucasian
subjects. Guanfacine XR was generally well tolerated and safety profiles were
similar for Japanese and Caucasian subjects.
PMID- 28421381
TI - Lactase Non-persistence and Lactose Intolerance.
AB - PURPOSE OF REVIEW: To evaluate the clinical and nutritional significance of
genetically determined lactase non-persistence and potential lactose and milk
intolerance in 65-70% of the world's adult population. RECENT FINDINGS: Milk
consumption is decreasing in the USA and is the lowest in countries with a high
prevalence of lactase non-persistence. The dairy industry and Minnesota
investigators have made efforts to minimize the influence of lactose intolerance
on milk consumption. Some lactose intolerant individuals, without co-existent
irritable bowel syndrome, are able to consume a glass of milk with a meal with no
or minor symptoms. The high frequency of lactase persistence in offspring of
Northern European countries and in some nomadic African tribes is due to
mutations in the promoter of the lactase gene in association with survival
advantage of milk drinking. Educational and commercial efforts to improve calcium
and Vitamin D intake have focused on urging consumption of tolerable amounts of
milk with a meal, use of lowered lactose-content foods including hard cheeses,
yogurt, and lactose-hydrolyzed milk products.
PMID- 28421384
TI - The efficacy of Guolin-Qigong on the body-mind health of Chinese women with
breast cancer: a randomized controlled trial.
AB - PURPOSE: This study was to evaluate the efficacy of a complementary Chinese
treatment modality Guolin-Qigong (GLQG) for patients with breast cancer on the
body-mind health. METHODS: A randomized controlled clinical trial was conducted
among 158 women with breast cancer. Subjects were randomized to receive GLQG
(test group) versus a physical stretching program (control group) following
conventional treatment for breast cancer. GLQG and stretching interventions were
performed twice a week over 24 weeks. The primary outcome was the change in
quality of life (QoL). Secondary outcome measures included anxiety, depression,
and clinical indicators. All participants were assessed at four time-points, at
the beginning of the study (T1), after 12 weeks of the intervention (T2),
immediately after 24-week intervention (T3), and at 48-week follow-up visit (T4).
RESULTS: Improvements in QoL were evident in both groups but the test group fared
better than the control group at the 12th week (P < 0.01) and particularly in
emotional well-being (P < 0.01) and breast cancer-specific well-being (P <
0.001). The test group showed an improvement in anxiety levels (P < 0.01),
whereas the control group showed improvements in depression (P < 0.05) but there
was no significant difference between groups (P > 0.05). Both groups showed
improvements in immunological function and the test group fared better than the
control in TNF-alpha levels (P < 0.05). The results in subjects who practiced
more than 4 times and 6 h per week were similar to that of all subjects; however,
the improvement in anxiety in the GLQG group was more obvious. There are positive
correlations between QoL and anxiety and depression. CONCLUSIONS: Both GLQG and
physical stretching are beneficial during recovery following breast cancer. GLQC
was more effective in terms of Qol improvements than physical stretching. Both
programs brought improvements in anxiety or depression but had were comparable.
GLQC group had a greater effect on immunological function than physical exercise.
PMID- 28421385
TI - In vitro and in vivo anti-tumor effects of selected platinum(IV) and dinuclear
platinum(II) complexes against lung cancer cells.
AB - In the present study, cytotoxic effects of cisplatin, the most usually used
chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)]
(en = ethylenediamine) and [PtCl4(dach)]) (dach = (+/-)-trans-1,2
diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(MU
pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(MU-4,4'
bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(MU-1,2
bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and
murine lung cancer cells, to determine anti-tumor potential of newly synthesized
platinum-based drugs in the therapy of lung cancer. Results obtained by MTT [3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], Lactate
dehydrogenase and Annexin V/Propidium Iodide assays showed that, among all tested
complexes, [PtCl4(en)] had the highest cytotoxicity against human and murine lung
carcinoma cells in vitro. [PtCl4(en)] showed significantly higher cytotoxicity
then cisplatin in all tested concentrations, mainly by inducing apoptosis in lung
cancer cells. [PtCl4(en)] was well tolerated in vivo. Clinical signs of
[PtCl4(en)]-induced toxicity, such as changes in food, water consumption or body
weight, nephrotoxicity or hepatotoxicity was not observed in [PtCl4(en)]-treated
mice. [PtCl4(en)] managed to increase presence of CD45+ leukocytes, including
F4/80+ macrophages, CD11c+ dendritic cells, CD4+ helper and CD8+ cytotoxic T
cells (CTLs) in the lungs, cytotoxic NK, NKT and CTLs in the spleens of tumor
bearing mice, resulting with reduction of metastatic lesions in the lungs,
indicating its potential to stimulate anti-tumor immune response in vivo. Due to
its anti-tumor cytotoxicity, biocompatibility, and potential for stimulation of
anti-tumor immune response, [PtCl4(en)] may be a good candidate for further
testing in the field of medicinal chemistry.
PMID- 28421386
TI - Technology assessment and cost-effectiveness in orthopedics: how to measure
outcomes and deliver value in a constantly changing healthcare environment.
AB - PURPOSE OF REVIEW: The purpose of this study is to review the basic concepts of
healthcare value, patient outcome measurement, and cost-effectiveness analyses as
they relate to the introduction of new surgical techniques and technologies in
the field of orthopedic surgery. RECENT FINDINGS: An increased focus on financial
stewardship in healthcare has resulted in a plethora of cost-effectiveness and
patient outcome research. Recent research has made great progress in identifying
orthopedic technologies that provide exceptional value and those that do not meet
adequate standards for widespread adoption. As the pace of technological
innovation advances in lockstep with an increased focus on value, orthopedic
surgeons will need to have a working knowledge of value-based healthcare decision
making. Value-based healthcare and cost-effectiveness analyses can aid orthopedic
surgeons in making ethical and fiscally responsible treatment choices for their
patients.
PMID- 28421388
TI - Preferential distribution of nuclear MAPK signal in alpha/beta core neurons
during long-term memory consolidation in Drosophila.
PMID- 28421387
TI - Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins.
AB - There are many factors that can influence the pharmacokinetics (PK) of a mAb or
Fc-fusion molecule with the primary determinant being FcRn-mediated recycling.
Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a
variety of therapeutic antibodies with significantly enhanced half-life or
ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc
fusion protein can have a significant impact on the PK of these molecules. mAb
charge can be important and variants with pI values of 1-2 unit difference are
likely to impact PK with lower pI values being favorable for a longer half-life.
Most mAbs display target mediated drug disposition (TMDD), which can have
significant consequences on the study designs of preclinical and clinical
studies. The PK of mAb can also be influenced by anti-drug antibody (ADA)
response and off-target binding, which require careful consideration during the
discovery stage. mAbs are primarily absorbed through the lymphatics via
convection and can be conveniently administered by the subcutaneous (sc) route in
large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb
can be reasonably estimated using cynomolgus monkey data and allometric scaling
methods.
PMID- 28421389
TI - Preparation and biocompatibility of demineralized bone matrix/sodium alginate
putty.
AB - Demineralized bone matrix (DBM) powder is widely used for bone regeneration due
to its osteoinductivity and osteoconductivity. However, difficulties with
handling, tendency to migrate from graft sites and lack of stability after
surgery sometimes limit the clinical utility of this material. In this work, the
possibility of using sodium alginate (ALG) carrier to deliver DBM powder was
assessed. DBM-ALG putty with the DBM:ALG weight ratio of 5:5, 6:4, 7:3, 8:2 were
prepared, respectively. The properties of the formed composite, including
discrete degree, washout property, pH, equilibrium swelling as well as
cytotoxicity in vivo, were adopted to ascertain the optimal ratio of DBM and ALG.
The discrete diameter increased from 1.25 cm (5:5) to 2.08 cm (8:2) with the
increase of DBM content. There was significant difference between the 8:2 group
and the other groups in discrete diameter. The ratio of DBM had a significant
effect on the swelling value. The pH of composites showed an increase trend with
the DBM ratio's increase, when the ratio reached 7:3, the pH (7.22) was
approximately equal to the body fluid. The proliferation of MC3T3-E1 cells was
inhibited in the 5:5, 6:4 and 7:3 groups, while a slightly increased in the 8:2
group. The DBM-ALG with the optimal ratio of 7:3 was confirmed based on the
results of the above mentioned. The histocompatibility of DBM-ALG (7:3) was
examined using a rat model in which the materials were implanted subcutaneously,
compared with the polyethylene, ALG and DBM. The study in vivo showed DBM-ALG
(7:3) had a lower inflammatory response than DBM, a higher vascularization than
ALG. The osteoinduction of DBM-ALG (7:3) was evaluated by co-culturing with MC3T3
E1 in vitro, compared with the DMEM, ALG and DBM. The results indicated
calcification area in the DBM-ALG group was similar to that in the DBM group,
larger than ALG group and DMEM group. The DBM-ALG (7:3) putty is promising as a
directly injectable graft for repair of bone defect.
PMID- 28421390
TI - Ofatumumab combined with chlorambucil for previously untreated chronic
lymphocytic leukemia: a phase I/II, open-label study in Japan.
AB - Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low
toxicity treatments. Internationally, the standard treatment for such patients is
chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in
Japan. The aim of the present study was to evaluate the safety, efficacy and
pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese
patients with previously untreated CLL who were inappropriate for fludarabine
based therapy. Ten patients were enrolled and treated in this study, all of whom
received at least one dose of the study drugs. The tolerability of the treatment
was confirmed initially with three patients. The overall response rate was 50%,
as determined by the Independent Review Committee (IRC) with computerized
tomography. All patients were alive at follow-up, and only one patient had
progressive disease. The most common treatment-related adverse events (AEs) were
thrombocytopenia (n = 10), neutropenia (n = 9) and rash (n = 6). One grade 3
serious AE related to the study drug occurred (hypoxia). The results indicate
that ofatumumab combined with chlorambucil is an effective treatment for Japanese
CLL patients, with a manageable safety profile.
PMID- 28421391
TI - Epidemiology of Suicide Attempts among Youth Transitioning to Adulthood.
AB - Suicide is the second leading cause of death for older adolescents and young
adults. Although empirical literature has identified important risk factors of
suicidal behavior, it is less understood if changes in risk factors correspond
with changes in suicide risk. To address this knowledge gap, we assessed if there
were different trajectories of suicidal behavior as youth transition into young
adulthood and determined what time-varying risk factors predicted these
trajectories. This study used four waves of data spanning approximately 13 years
from the National Longitudinal Study of Adolescent Health. The sample included
9027 respondents who were 12-18 years old (M = 15.26; SD = 1.76) at Wave 1, 50%
male, 17% Hispanic, and 58% White. The results indicated that 93.6% of the sample
had a low likelihood for suicide attempts across time, 5.1% had an elevated
likelihood of attempting suicide in adolescence but not young adulthood, and 1.3%
had an elevated likelihood of attempting suicide during adolescence and
adulthood. The likelihood of a suicide attempt corresponded with changes on
depression, impulsivity, delinquency, alcohol problems, family and friend suicide
history, and experience with partner violence. Determining how suicide risk
changes as youth transition into young adulthood and what factors predict these
changes can help prevent suicide. Interventions targeting these risk factors
could lead to reductions in suicide attempts.
PMID- 28421393
TI - Modified nomogram for derivation of renal threshold phosphate concentration.
PMID- 28421392
TI - Combination of sacral nerve and tibial nerve stimulation for treatment of bladder
overactivity in pigs.
AB - PURPOSE: Sacral nerve and tibial nerve stimulation have been singly used to treat
overactive bladder (OAB). This study evaluated the effects of both combined
stimulation on treating bladder overactivity in pigs and explored a novel
treatment modality for OAB. METHODS: An implant-driven stimulator of the S3
spinal nerve was implanted in 5 pigs. The contralateral tibial nerve was
stimulated by an external stimulator. Multiple cystometrograms were performed to
determine the effects of single nerve stimulation and combination sacral nerve
stimulation (SNS) and tibial nerve stimulation (TNS) on the micturition reflex by
infusing normal saline (NS) or acetic acid (AA). RESULTS: AA-induced bladder
overactivity significantly reduced bladder capacity (BC) to 16.3 +/- 2.2% of the
NS control level (389.4 +/- 27.68 ml; P < 0.01). When given a single stimulation,
both SNS and TNS significantly increased the BC to 39.2 +/- 1.6% and 34.9 +/-
5.0% of the NS control level (P < 0.01), respectively. Combined SNS and TNS
significantly increased the BC to 50.2 +/- 5.2% of the NS control level (P <
0.01) and induced a superior inhibitory effect than SNS or TNS alone (P < 0.05).
CONCLUSIONS: Combination SNS and TNS induced a superior inhibitory effect on
bladder overactivity in pigs compared to single stimulation and thus could be a
novel treatment modality for OAB.
PMID- 28421394
TI - Waveform Integrity in Atrial Fibrillation: The Forgotten Issue of Cardiac
Electrophysiology.
AB - Atrial fibrillation (AF) is the most common arrhythmia in clinical practice with
an increasing prevalence of about 15% in the elderly. Despite other alternatives,
catheter ablation is currently considered as the first-line therapy for the
treatment of AF. This strategy relies on cardiac electrophysiology systems, which
use intracardiac electrograms (EGM) as the basis to determine the cardiac
structures contributing to sustain the arrhythmia. However, the noise-free
acquisition of these recordings is impossible and they are often contaminated by
different perturbations. Although suppression of nuisance signals without
affecting the original EGM pattern is essential for any other later analysis, not
much attention has been paid to this issue, being frequently considered as
trivial. The present work introduces the first thorough study on the significant
fallout that regular filtering, aimed at reducing acquisition noise, provokes on
EGM pattern morphology. This approach has been compared with more refined
denoising strategies. Performance has been assessed both in time and frequency by
well established parameters for EGM characterization. The study comprised
synthesized and real EGMs with unipolar and bipolar recordings. Results reported
that regular filtering altered substantially atrial waveform morphology and was
unable to remove moderate amounts of noise, thus turning time and spectral
characterization of the EGM notably inaccurate. Methods based on Wavelet
transform provided the highest ability to preserve EGM morphology with
improvements between 20 and beyond 40%, to minimize dominant atrial frequency
estimation error with up to 25% reduction, as well as to reduce huge levels of
noise with up to 10 dB better reduction. Consequently, these algorithms are
recommended as a replacement of regular filtering to avoid significant
alterations in the EGMs. This could lead to more accurate and truthful analyses
of atrial activity dynamics aimed at understanding and locating the sources of
AF.
PMID- 28421395
TI - Clinical interpretation of asymptomatic medial collateral ligament injury
observed on magnetic resonance imaging in adolescent baseball players.
AB - PURPOSE: Magnetic resonance imaging (MRI) of medial collateral ligament (MCL)
injury of the elbow was often observed in asymptomatic adolescent baseball
players. We aimed to clarify the clinical interpretation of "asymptomatic MCL
injury observed on MRI" by comparing MRI, ultrasonography (US), and physical
findings. MATERIALS AND METHODS: Sixty-four asymptomatic adolescent baseball
players (mean 11.2 years) were enrolled. An open-type 0.2T MRI was used. MCL
function was evaluated by measuring the opening of the ulnohumeral joint using
US. Physical findings included MCL tenderness, the moving valgus test, and the
Milking test. The correlation between MRI and US, and MRI and physical findings
were analyzed. RESULTS: Thirty-four subjects (53.1%) showed MCL injury by MRI.
The mean laterality of the ulnohumeral joint opening showed no significant
difference (P = 0.16) between the group with (0.29 +/- 1.06 mm) and without (0.08
+/- 0.96 mm) MCL injury on MRI. There was no correlation between MRI and physical
findings except for a weak correlation between subjects with positive Milking
test and MCL injury on MRI (phi coefficient = 0.3, P = 0.02). CONCLUSION:
'Asymptomatic MCL injury on MRI' had little correlation to ligament dysfunction.
It might represent the transition period to MCL thickening called "adaptation."
PMID- 28421396
TI - 11C-methionine PET/CT findings in benign brain disease.
AB - 11C-methionine (MET) is one of the most commonly used positron emission
tomography (PET) tracers for evaluation of malignant brain tumor, with MET-PET
being a sensitive technique for visualization of primary and recurrent malignant
brain tumors. However, previous reports have demonstrated MET uptake in lesions
associated with benign brain diseases. These diseases usually show an increase in
MET uptake similar to that of malignant tumors. This pitfall in MET-PET image
interpretation is important not only for nuclear medicine professionals, but also
for radiologists. In this review, we demonstrate the imaging characteristics of
MET uptake in benign brain disease, and recommend physician interpretation of
imaging findings and disease characteristics for optimal patient management.
Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical
operations.
PMID- 28421397
TI - Comparison between the four-field box and field-in-field techniques for conformal
radiotherapy of the esophagus using dose-volume histograms and normal tissue
complication probabilities.
AB - PURPOSE: We evaluated and compared the performance of the field-in-field (FIF) to
that of the four-field box (4FB) technique regarding dosimetric and
radiobiological parameters for radiotherapy of esophageal carcinoma. MATERIALS
AND METHODS: Twenty patients with esophageal cancer were selected. For each
patient, two treatment plans were created: 4FB and FIF. The parameters compared
included the conformity index (CI), homogeneity index (HI), D mean, D max, tumor
control probability (TCP), V 20Gy and V 30Gy of the heart and lungs, normal
tissue complication probability (NTCP), and monitor units per fraction (MU/fr).
RESULTS: A paired t-test analysis did not show any significant differences (p >
0.05) between the two techniques in terms of the CI and TCP. However, the HI
significantly improved when the FIF was applied. D max of the PTV, lung, and
spinal cord were also significantly better with the FIF. Moreover, the lung V
20Gy as well as the NTCPs of the lung and spinal cord significantly reduced when
the FIF was used, and the MU/fr was significantly decreased. CONCLUSIONS: The FIF
showed evident advantages over 4FB: a more homogeneous dose distribution, lower D
max values, and fewer required MUs, while it also retained PTV dose conformality.
FIF should be considered as a simple technique to use clinically in cases with
esophageal malignancies, especially in clinics with no IMRT.
PMID- 28421398
TI - Supradescemetic voriconazole injection for Candida parapsilosis keratitis.
AB - PURPOSE: To describe a technique for intracorneal application of voriconazole
into the supradescemetic space in a case of deep recalcitrant Candida
parapsilosis keratitis of a penetrating cornea graft. METHODS: A deep
intracorneal incision reaching the center of the corneal infiltrate was created
with a 20-gauge MVR blade. Then, a 27-gauge hydrodissection cannula was inserted
deep into the corneal pocket, and 0.1 ml of voriconazole 0.5 mg/ml was injected
until a bullous detachment of Descemet membrane (DM) covered 1/3 of the graft's
area. DM detachment was documented by anterior segment optical coherence
tomography (AS-OCT). RESULTS: AS-OCT confirmed the creation of a drug depot in
the supradescemetic space, which partially regressed during the following hours;
24 h after the injection, a complete reattachment of DM was documented. After 4
weeks, the stromal infiltrate has cleared completely and no signs of recurrence
were observed 3 months after injection. CONCLUSION: In the present case, the
supradescemetic voriconazole injection led to resolution of a deep recalcitrant
fungal infiltrate. The herein described technique could be tried in similar
cases, where an intrastromal injection is indicated, as it may offer a larger
intracorneal drug depot.
PMID- 28421399
TI - Effect of intravitreal aflibercept (Eylea(r)) on retrobulbar hemodynamics in
patients with neovascular age-related macular degeneration.
AB - PURPOSE: To investigate the short-term effect of single intravitreal aflibercept
injection on retrobulbar blood flow in patients with neovascular age-related
macular degeneration (nAMD). METHODS: Twenty eyes of 20 patients with nAMD
scheduled for single intravitreal aflibercept (Eylea(r)) injection and 20 fellow
eyes (uninjected) were enrolled in this prospective interventional study. The
hemodynamic parameters of the ophthalmic artery (OA), central retinal artery
(CRA) and posterior ciliary artery (PCA) comprising peak systolic velocity (PSV),
end-diastolic velocity (EDV), and resistive index (RI) were measured by using
color Doppler ultrasonography (CDU) in both injected and uninjected fellow eyes
at baseline and 1 week after the injection. RESULTS: The measured first-week
values of PSV and EDV in the CRA, OA and PCA showed a statistically significant
reduction when comparing baseline values in both injected and uninjected fellow
eyes (p = 0.0001). Also, it was found a significant increase in the post
injection RI values of all the CRA, OA, PCA in injected eye and OA in the
uninjected eye (p = 0.0001). There was any significant difference between pre-
and post-injection RI values of the CRA and PCA in the fellow eyes (p = 0.137, p
= 0.736, respectively). CONCLUSION: Single intravitreal administration of
aflibercept alters retrobulbar blood flow velocities (BFVs) in both injected and
uninjected fellow eyes in the short-term period.
PMID- 28421400
TI - A multistage-dialysis microdevice for extraction of cryoprotectants.
AB - In this study, we present a multistage-dialysis microdevice (MDM) for extraction
of cryoprotectants (CPAs) from a CPA-laden cell suspension. We confirmed the
functions of the key designs of the MDM using a fluorescence solution, we
assessed the performance of the MDM by using the MDM to unload glycerin from
glycerin-loaded swine erythrocytes, and we investigated the effects of the cell
suspension flow rate, glycerin concentration, cell density, and membrane pore
size on the clearance efficiency of glycerin (CG), the survival rate of cells
(SC), and the recovery rate of cells (RC). Under the designed conditions, CG, SC,
and RC reached ~60%, ~90%, and ~70%, respectively. In addition, a high flow rate
causes high SC and RC but a low CG. For a low glycerin concentration, CG, SC, and
RC are all high. If a low cell density or a large pore membrane is used, CG is
high, whereas both SC and RC are low. This work provides insight into the
development of microfluidic devices for the inline extraction of cryoprotectants
from a small volume of cryopreserved cells prior to the use of the cells in lab
on-a-chip applications.
PMID- 28421401
TI - Liquid marbles as bioreactors for the study of three-dimensional cell
interactions.
AB - Liquid marble as a bioreactor platform for cell-based studies has received
significant attention, especially for developing 3D cell-based assays. This
platform is particularly suitable for 3D in-vitro modeling of cell-cell
interactions. For the first time, we demonstrated the interaction of olfactory
ensheathing cells (OECs) with nerve debris and meningeal fibroblast using liquid
marbles. As the transplantation of OECs can be used for repairing nerve injury,
degenerating cell debris within the transplantation site can adversely affect the
survival of transplanted OECs. In this paper, we used liquid marbles to mimic the
hostile 3D environment to analyze the functional behavior of the cells and to
form the basis for cell-based therapy. We show that OECs interact with debris and
enhanced cellular aggregation to form a larger 3D spheroidal tissue. However,
these spheroids indicated limitation in biological functions such as the
inability of cells within the spheroids to migrate out and adherence to
neighboring tissue by fusion. The coalescence of two liquid marbles allows for
analyzing the interaction between two distinct cell types and their respective
environment. We created a microenvironment consisting of 3D fibroblast spheroids
and nerve debris and let it interact with OECs. We found that OECs initiate
adherence with nerve debris in this 3D environment. The results suggest that
liquid marbles are ideal for developing bioassays that could substantially
contribute to therapeutic applications. Especially, insights for improving the
survival and adherence of transplanted cells.
PMID- 28421403
TI - Erratum to: CcpNmr AnalysisAssign: a flexible platform for integrated NMR
analysis.
PMID- 28421402
TI - The Effect of Losses Disguised as Wins and Near Misses in Electronic Gaming
Machines: A Systematic Review.
AB - Near misses and losses disguised as wins have been of interest to gambling
researchers and policymakers for many years (e.g., Griffiths in J Gambl Stud
9(2):101-120, 1993). This systematic literature review describes the behavioural,
psychological, and psychobiological effects of near misses and losses disguised
as wins (LDWs) in an effort to evaluate their precise influence on the player and
to highlight areas requiring further investigation. A systematic search for
relevant studies was conducted using Scopus, PubMed, PsycINFO, ProQuest Sociology
databases, and the Gambling Research Exchange Ontario Knowledge Repository. A
total of 51 (from an initial pool of 802) experimental peer-reviewed studies
using human participants were found between 1991 and 2015. The systematic review
revealed that near misses motivate continued play, but have varying effects on
the emotional state or betting behaviour of the player. Near miss events were
also shown to be associated with elevated skin conductance levels and diffuse
activity across the brain, most consistently in areas processing reinforcement
and reward. Re-examination of the studies of near misses events after classifying
the type of game feedback suggested that the effectiveness of near misses is
related to the phenomenology of a near miss itself rather than as a response to
auditory or visual feedback provided by a slot machine. In contrast to near
misses, the presence of LDWs was found to relate to an overestimation of how much
a player is actually winning and was consistently viewed as an exciting event.
The effect of LDWs appears to be driven by the presence of visuals and sounds
most often associated with a true win. Practical implications and directions for
future research are also discussed.
PMID- 28421404
TI - Characterization of ZnO Nanoparticles using Superconducting Tunnel Junction
Cryodetection Mass Spectrometry.
AB - Zinc oxide (ZnO) nanoparticles coated with either n-octylamine (OA) or alpha
amino poly(styrene-co-acrylonitrile) (PSAN) ligands (L) have been analyzed using
laser desorption/ionization and matrix assisted laser desorption/ionization
(MALDI) time-of-flight (TOF) superconducting tunnel junction (STJ) cryodetection
mass spectrometry. STJ cryodetection has the advantage of high m/z detection and
allows for the determination of average molecular weights and dispersities for
500-600 kDa ZnO-L nanoparticles. The ability to detect the relative energies
deposited into the STJs has allowed for investigation of ZnO-L metastable
fragmentation. ZnO-L precursor ions gain enough internal energy during the MALDI
process to undergo metastable fragmentation in the flight tube. These fragments
produced a lower energy peak, which was assigned as ligand-stripped ZnO cores
whereas the individual ligands were at too low of an energy to be observed. From
these STJ energy resolved peaks, the average weight percentage of inorganic
material making up the nanoparticle was determined, where ZnO-OA and ZnO-PSAN
nanoparticles are comprised of ~62% and ~68% wt ZnO, respectively. In one
example, grafting densities were calculated based on the metastable fragmentation
of ligands from the core to be 16 and 1.1 nm-2 for ZnO-OA and ZnO-PSAN,
respectively, and compared with values determined by thermogravimetric analysis
(TGA) and transmission electron microscopy (TEM). Graphical Abstract ?.
PMID- 28421405
TI - Differential Fragmentation of Mobility-Selected Glycans via Ultraviolet
Photodissociation and Ion Mobility-Mass Spectrometry.
AB - The alternative dissociation pathways initiated by ultraviolet photodissociation
(UVPD) compared with collision-induced dissociation (CID) may provide useful
diagnostic fragments for biomolecule identification, including glycans. However,
underivatized glycans do not commonly demonstrate strong UV absorbance, resulting
in low fragmentation yields for UVPD spectra. In contrast to UVPD experiments
that leverage covalent modification of glycans, we detail the capacity of metal
adduction to yield comparatively rich UVPD fragmentation patterns and enhance
separation factors for an isomeric glycan set in a drift tube ion mobility
system. Ion mobility and UVPD-MS spectra for two N-acetyl glycan isomers were
examined, each adducted with sodium or cobalt cations, with the latter providing
fragment yield gains of an order of magnitude versus sodium adducts. Furthermore,
our glycan analysis incorporated front-end ion mobility separation such that the
structural glycan isomers could still be identified even as a mixture and not
simply composite spectra of isomeric standards. Cobalt adduction proved
influential in the glycan separation by yielding an isomer resolution of 0.78
when analyzed simultaneously versus no discernable separation obtained with the
sodium adducts. It is the combined enhancement of both isomeric drift time
separation and isomer distinction with improved UVPD fragment ion yields that
further bolster multivalent metal adduction for advancing glycan IM-MS
experiments. Graphical Abstract ?.
PMID- 28421406
TI - Whole body MRI with qualitative and quantitative analysis of DWI for assessment
of bone marrow involvement in lymphoma.
AB - AIM: Our study aimed to investigate the role of qualitative and quantitative
whole body MRI with DWI for assessment of bone marrow involvement (BMI) in newly
diagnosed lymphoma using FDG PET-CT and bone marrow biopsy (BMB) as reference
standard. MATERIALS AND METHODS: We retrospectively evaluated 56 patients with
newly diagnosed lymphoma (21 Hodgkin's lymphoma and 35 non-Hodgkin's lymphoma)
who underwent random unilateral BMB, FDG PET-CT and Wb-MRI-DWI for initial
staging. In a patient-based analysis, results of Wb-MRI-DWI were compared with
FDG PET-CT and BMB. For quantitative analysis, mean ADC values of posterior iliac
crest were correlated with BMI and bone marrow cellularity. RESULTS: WB-MR-DWI
obtained excellent concordance with FDG PET-CT both in HL (k = 1.000; 95% CI
1.000-1.000) and in DLBCL (k = 1.000; 95% CI 1.000-1.000). In other NHL, WB-MRI
DWI obtained a good correlation with BMB (k = 0.611; 95% CI 0.295-0.927) while
FDG PET-CT had poor concordance (k = 0.067; 95% CI 0.372-0.505). WB-MR-DWI has no
false negative errors but 4 false positive results consisting in focal lesions
consensually reported by FDG PET-CT and resolved after therapy. No significant
correlation between ADC mean value and BMI was found (p = 0.0586). CONCLUSION:
Our data suggest that Wb-MRI-DWI is a valid technique for BMI assessment in
lymphoma patients, thanks to its excellent concordance with FDG PET-CT and good
concordance with BMB (superior than FDG PET-CT). If further investigations will
confirm our results on larger patient groups, it could become a useful tool in
the clinical workup.
PMID- 28421407
TI - Treatment of non-healing post-surgical fistula: a challenge for interventional
radiologist.
PMID- 28421408
TI - Pharmacological and Non-pharmacological Treatment for Decompensated Heart
Failure: What Is New?
AB - PURPOSE OF THE REVIEW: Acute heart failure (AHF) is a life-threatening clinical
condition that requires prompt medical attention. The aim of the current review
is to summarise the results of recent clinical trials conducted in patients with
AHF. RECENT FINDINGS: Several novel compounds have apparently beneficial acute
effects on cardiovascular haemodynamics and patients' symptoms, but their
administration has not yet translated into improved survival and has been
deleterious in some cases. The management of patients with AHF is challenging and
reflects the heterogeneity of patient's presentation, the complexity and severity
of a multi-organ syndrome, and the limited therapeutic options, usually
restricted to a combination of diuretics and vasodilators. Ongoing trials of
novel treatments may provide evidence of an effect on outcomes.
PMID- 28421409
TI - Six-Minute Walk Test for Assessing Physical Functional Capacity in Chronic Heart
Failure.
AB - PURPOSE OF THE REVIEW: The six-minute walk test (6MWT) is a submaximal exercise
test for evaluating physical functional capacity. This review aims to report the
research on the use of the 6MWT in chronic heart failure (CHF) that has been
published in the past 5 years. RECENT FINDINGS: The 6MWT distance does not
accurately reflect peak VO2. Minimal clinically important difference in the 6MWT
distance, and additional measurements, such as heart rate recovery, can assist in
the interpretation of the 6MWT distance, so management decisions can be made.
Incorporating mobile apps and information technology in measuring the 6MWT
distance extends the usefulness of this simple walk test and improve remote
monitoring of patients with CHF. The 6MWT is a useful tool in CHF programs.
However, interpretation of the 6MWT distance must be with caution. With the
advancement in technology, the 6MWT has the potential to facilitate the
monitoring of people living in rural and remote areas.
PMID- 28421410
TI - Antiparasitic Sesquiterpenes from the Cameroonian Spice Scleria striatinux and
Preliminary In Vitro and In Silico DMPK Assessment.
AB - The antiparasitic activity and preliminary in vitro and in silico drug metabolism
and pharmacokinetic (DMPK) assessment of six isomeric sesquiterpenes (1-6),
isolated from the Cameroonian spice Scleria striatinux De Wild (Cyperaceae) is
reported. The study was prompted by the observation that two of the compounds (1
and 2) exhibited varying levels of antiparasitic activity on Plasmodium
falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania
donovani. The in silico method employed a total of 46 descriptors, calculated
using Schrodinger QikProp software. 18 of these molecular descriptors that are
often used to predict DMPK profiles of drug-like molecules have been selected for
discussion. In vitro experimental assessment of metabolic stability made use of
human liver microsomes, which was used to correlate theoretical predictions with
experimental findings. Overall, the test compounds have been found to have
acceptable physicochemical properties and fall within the ranges associated with
"drug-like" molecules. Moreover, the compounds exhibited minimal degradation in
incubations with human liver microsomes. Although some of these compounds have
been reported previously (1, 2, 4 and 5), this is the first report on their
antiparasitic activities, as well as assessment of their DMPK profiles. These
results have therefore provided a window for further development of this novel
class of sesquiterpene molecules as potential antiparasitic drugs.
PMID- 28421411
TI - Seleno-short-chain chitosan induces apoptosis in human non-small-cell lung cancer
A549 cells through ROS-mediated mitochondrial pathway.
AB - Seleno-short-chain chitosan (SSCC) is a synthesized chitosan derivative. In this
study, antitumor activity and underlying mechanism of SSCC on human non-small
cell lung cancer A549 cells were investigated in vitro. The MTT assay showed that
SSCC could inhibit cell viability in a dose- and time-dependent manner, and 200
MUg/ml SSCC exhibited significantly toxic effects on A549 cells. The cell cycle
assay showed that SSCC triggered S phase cell cycle arrest in a dose- and time
dependent manner, which was related to a downregulation of S phase associated
cyclin A. The DAPI staining and Annexin V-FITC/PI double staining identified that
the SSCC could induce A549 cells apoptosis. Further studies found that SSCC led
to the generation of reactive oxygen species (ROS) and the disruption of
mitochondrial membrane potential (MMP) by DCFH-DA and Rhodamin 123 staining,
respectively. Meanwhile, free radical scavengers N-acetyl-L-cysteine (NAC)
pretreatment confirmed that SSCC-induced A549 cells apoptosis was associated with
ROS generation. Furthermore, real-time PCR and western blot assay showed that
SSCC up-regulated Bax and down-regulated Bcl-2, subsequently incited the release
of cytochrome c from mitochondria to cytoplasm, activated the increase of cleaved
caspase 3 and finally induced A549 cells apoptosis in vitro. In general, the
present study demonstrated that SSCC induced A549 cells apoptosis via ROS
mediated mitochondrial apoptosis pathway.
PMID- 28421412
TI - Bioactive compounds and antioxidant activity exhibit high intraspecific
variability in Pleurotus ostreatus mushrooms and correlate well with cultivation
performance parameters.
AB - Experimental data related with oyster mushroom production and nutritional
properties usually derive from the examination of only one strain, and hence
their representativeness/usefulness is questionable. This work aims at assessing
intraspecific variability in Pleurotus ostreatus by studying 16 strains, under
the same conditions, in respect to essential cultivation and mushroom quality
aspects, and by defining the impact of intrinsic/genetic factors on such
parameters. Hence, mushroom yield, earliness, crop length, biological efficiency,
productivity, and their content in selected macro and microconstituents (e.g.
fatty acids, sterols, individual phenolic compounds, terpenic acids, glucans) as
well as their antioxidant properties (i.e., antiradical activity, ferric reducing
potential, inhibition of serum oxidation) were assayed. The effect of
intrinsic/genetic factors was evident, especially as regards earliness, yield of
each production flush and mushroom weight, whereas biological efficiency was not
particularly influenced by the cultivated strain. Moreover, phenolics, ergosterol
and antiradical activity demonstrated significant variability among strains in
contrast to what was observed for fatty acids, beta-glucans and ferric reducing
potential. The observed heterogeneity reveals the limitations of using a low
number of strains for evaluating mushroom production and/or their content in
bioactive compounds, and as evidenced, it is valuable for breeding and commercial
purposes.
PMID- 28421413
TI - Substrate-Induced Conformational Changes of the Tyrocidine Synthetase 1
Adenylation Domain Probed by Intrinsic Trp Fluorescence.
AB - Nonribosomal peptide synthetases (NRPS) are multifunctional proteins that
catalyze the synthesis of the peptide products with enormous biological
potential. The process of biosynthesis starts with the adenylation (A) domain,
which during the catalytic cycle undergoes extensive structural rearrangements.
In this paper, we present the first study of the tyrocidine synthetase 1 A-domain
(TycA-A) fluorescence properties. The TycA-A protein contains five potentially
fluorescent Trp residues at positions 227, 301, 323, 376 and 406. The
contribution of each Trp to the TycA-A emission was determined using protein
variants bearing single Trp to Phe substitutions. The accessibility of the Trp
side chains during adenylation showed that only W227 is affected by substrate
binding. The protein variant containing solely fluorescent W227 residue was
constructed and further used as a probe to explore the binding effect of
different non-cognate amino acid substrates. The results indicate a different
accessibility of W227 residue in the presence of non-cognate amino acids, which
might offer an explanation for the higher aminoacyl-adenenylate leakage. Overall,
our results suggest that intrinsic tryptophan fluorescence could be used as a
method to probe the effect of substrate binding on the local structure in NRPS
adenylation domains.
PMID- 28421414
TI - Polyclonal Antibodies in Microplates to Predict the Maximum Adsorption Activities
of Enzyme/Mutants from Cell Lysates.
AB - With microplate-immobilized polyclonal antibodies against a starting enzyme or
its active mutant bearing consistent accessible epitopes, the maximum activity of
an adsorbed enzyme/mutant (Vs) was predicted for comparison to recognize weakly
positive mutants. Rabbit antisera against Escherichia coli alkaline phosphatase
(ECAP) were fractionated with 33% ammonium sulfate to yield crude polyclonal
antibodies for conventional immobilization in 96-well microplates. The response
curve of the activities of ECAP/mutant adsorbed by the immobilized polyclonal
antibodies to protein quantities from a cell lysate was fit to an approximation
model to predict Vs. With 0.4 MUg crude polyclonal antibody for immobilization,
Vs was consistent for ECAP in cell lysates bearing fourfold differences in its
apparent specific activities when its abundance was greater than 0.9%. The ratio
of Vs of the mutant R168K to that of ECAP was 1.5 +/- 0.1 (n = 2), consistent
with that of their specific activities after affinity purification.
Unfortunately, the prediction of Vs with polyclonal antibodies that saturated
microplate wells was ineffective to Pseudomonas aeruginosa arylsulfatase bearing
less than 2% specific activity of ECAP. Therefore, with microplate-immobilized
polyclonal antibodies to adsorb enzyme/mutants from cell lysates, high-throughput
prediction of Vs was practical to recognize weakly-positive mutants of starting
enzymes bearing fairly-high activities.
PMID- 28421415
TI - A Tyrosine Residue Along with a Glutamic Acid of the Omega-Like Loop Governs the
Beta-Lactamase Activity of MSMEG_4455 in Mycobacterium smegmatis.
AB - Mycobacterial beta-lactamases are involved in exerting beta-lactam resistance,
though many of these proteins remain uncharacterized. Here, we have characterized
MSMEG_4455 of Mycobacterium smegmatis as a beta-lactamase using molecular,
biochemical and mutational techniques. To elucidate its nature in vivo and in
vitro, and to predict its structure-function relationship in silico analysis is
done. The MSMEG_4455 is cloned and expressed ectopically in a beta-lactamase
deficient Escherichia coli mutant to establish the in vivo beta-lactamase like
nature via minimum inhibitory concentration (MIC) determination. Likewise the in
vivo results, purified soluble form of MSMEG_4455 showed beta-lactam hydrolysis
pattern similar to group 2a penicillinase. In silico analyses of MSMEG_4455
reveal glutamic acid (E)193 and tyrosine (Y)194 of omega-like loop might have
importance in strengthening hydrogen bond network around the active-site, though
involvement of tyrosine is rare for beta-lactamase activity. Accordingly, these
residues are mutated to alanine (A) and phenylalanine (F), respectively. The
mutated proteins have partially lost their ability to exert beta-lactamase
activity both in vivo and in vitro. The Y194F mutation had more prominent effect
on the enzymatic activity. Therefore, we infer that Y194 is the key for beta
lactamase activity of MSMEG_4455.
PMID- 28421416
TI - Emergence of CTNNB1 mutation at acquired resistance to KIT inhibitor in
metastatic melanoma.
AB - PURPOSE: The KIT inhibitor, imatinib, has shown promising efficacy in patients
with KIT-mutated melanoma; however, acquisition of resistance to imatinib occurs
rapidly in the majority of patients. The mechanisms of acquired resistance to
imatinib in melanoma remain unclear. METHODS: We analyzed biopsy samples from
paired baseline and post-treatment tumor lesions in one patient with KIT-mutated
melanoma who had had an initial objective tumor regression in response to
imatinib treatment followed by disease progression 8 months later. RESULTS:
Targeted deep sequencing from post-treatment biopsy samples detected an
additional mutation in CTNNB1 (S33C) with original KIT L576P mutation. We
examined the functional role of the additional CTNNB1 S33C mutation in resistance
to imatinib indirectly using the Ba/F3 cell model. Ba/F3 cell lines transfected
with both the L576P KIT mutation and the CTNNB1 S33C mutation demonstrated no
growth inhibition despite imatinib treatment, whereas growth inhibition was
observed in the Ba/F3 cell line transfected with the L576 KIT mutation alone.
CONCLUSIONS: We report the first identification of the emergence of a CTNNB1
mutation that can confer acquired resistance to imatinib. Further investigation
into the causes of acquired resistance to imatinib will be essential to improve
the prognosis for patients with KIT-mutated melanoma.
PMID- 28421417
TI - Estimation of QT interval prolongation through model-averaging.
AB - The current method to analyze concentration-QT interval data, which is based on
predictions conditional on a best model, fails to take into account the
uncertainty of the model. Previous studies have suggested that failure to take
into account model uncertainty using a best model approach can result in
confidence intervals that are overly optimistic and may be too narrow.
Theoretically, more realistic estimates are obtained using model-averaging where
the overall point estimate and confidence interval are a weighted-average from a
set of candidate models, the weights of which are equal to each model's Akaike
weight. Monte Carlo simulation was used to determine the degree of narrowness in
the confidence interval for the degree of QT prolongation under a single
ascending dose and thorough QT trial design. Results showed that model averaging
performed as well as the best model approach under most conditions with no
numeric advantage to using a model averaging approach. No difference was observed
in the coverage of the confidence intervals when the best model and model
averaging was done by AIC, AICc, or BIC, although in certain circumstances the
coverage of the confidence interval themselves tended to be too narrow when using
BIC. Modelers can continue to use the best model approach for concentration-QT
modeling with confidence, although model averaging may offer more face validity,
may be of value in cases where there is uncertainty or misspecification in the
best model, and be more palatable to a non-technical reviewer than the best model
approach.
PMID- 28421418
TI - Lower urinary tract symptoms (LUTS) in males with type 2 diabetes recently
treated with SGLT2 inhibitors-overlooked and overwhelming? A retrospective case
series.
PMID- 28421419
TI - Phylogenetic analysis of avian infectious bronchitis virus isolates from Morocco:
a retrospective study (1983 to 2014).
PMID- 28421420
TI - The Future of Targeting FLT3 Activation in AML.
AB - Internal tandem duplications (ITD) and tyrosine-kinase domain (TKD) mutations of
the FMS-like tyrosine-kinase 3 (FLT3) can be found in up to one third of patients
with acute myeloid leukemia (AML) and confer a poor prognosis. First discovered
20 years ago, these mutations were identified as viable therapeutic targets, and
FLT3 tyrosine-kinase inhibitors (TKIs) have been in development for the last
decade with steadily increasing potency. However, FLT3-mutated AML often acquires
resistance to the growing armamentarium of FLT3 inhibitors through a variety of
mechanisms. In this review, we discuss the distinct clinical phenotype of FLT3
mutated AML, historically and currently available therapeutics, mechanisms of
resistance, ongoing trials, and future outlook at treatment strategies.
PMID- 28421421
TI - Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy.
AB - PURPOSE: In pituitary apoplexy (PA), there are preliminary reports on the
appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise
uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of
this study was to evaluate the incidence and clinical significance of SSMT in
patients with PA and a control group of surgically treated non-functioning
pituitary adenomas (NFPAs). METHODS: Retrospective review of clinical and imaging
variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured
on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was
defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic
regression was used to identify factors associated with SSMT. RESULTS: There were
50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or
surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in
the PA than NFPA groups (2.0 vs. 0.5 mm; p < 0.001). In multivariate analysis of
both the PA and NFPA groups, the presence of PA was the only factor associated
with SSMT (OR 0.043, 95% CI 0.012-0.16; p < 0.001). In multivariate analysis of
the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR
0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29,
95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The
incidence of SSMT is higher in patients with PA, especially during the acute
phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory
and/or infective changes.
PMID- 28421422
TI - Hepatitis C Virus-Genotype 3: Update on Current and Emergent Therapeutic
Interventions.
AB - PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved
the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent
infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or
hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge
compared with other genotypes. The dependence of the HCV life cycle on host lipid
metabolism suggests the possible utility of targeting host cellular factors for
combination anti-HCV therapy. We discuss current and emergent DAA regimens for
HCV-GT3 treatment. We then summarize recent research findings on the reliance of
HCV entry, replication, and virion assembly on host lipid metabolism. RECENT
FINDINGS: Current HCV treatment guidelines recommend the use of daclatasvir plus
sofosbuvir (DCV/SOF) or sofosbuvir plus velpatasvir (SOF/VEL) for the management
of GT3 based upon clinical efficacy [>=88% overall sustained virological response
(SVR)] and tolerability. Potential future DAA options, such as SOF/VEL co
formulated with GS-9857, also look promising in treating cirrhotic GT3 patients.
However, HCV resistance to DAAs will likely continue to impact the therapeutic
efficacy of interferon-free treatment regimens. Disruption of HCV entry by
targeting required host cellular receptors shows potential in minimizing HCV
resistance and broadening therapeutic options for certain subpopulations of GT3
patients. The use of cholesterol biosynthesis and transport inhibitors may also
improve health outcomes for GT3 patients when used synergistically with DAAs. Due
to the morbidity and mortality associated with HCV-GT3 infection compared to
other genotypes, efforts should be made to address current limitations in the
therapeutic prevention and management of HCV-GT3 infection.
PMID- 28421424
TI - Erratum to: Replacement of Marine Fish Oil with de novo Omega-3 Oils from
Transgenic Camelina sativa in Feeds for Gilthead Sea Bream (Sparus aurata L.).
PMID- 28421423
TI - The Effects of Direct-fed Microbial Supplementation, as an Alternative to
Antibiotics, on Growth Performance, Intestinal Immune Status, and Epithelial
Barrier Gene Expression in Broiler Chickens.
AB - The objective of this study was to investigate the effects of Bacillus subtilis
based probiotic supplementation in broiler chicken diets on growth performance,
feed efficiency, intestinal cytokine, and tight junction (TJ) protein mRNA
expression. Zero-day-old broiler chicks (n = 140) were randomly assigned to one
of five dietary treatments: basal diet (CON); basal diet supplemented with either
antibiotic bacitracin methylene disalicylate (BMD); or probiotics, namely, B.
subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104 + strain 747
(PB2), or B. subtilis strain 1781 + strain 747 (PB3). Body weight and feed intake
were measured at 14 days of age, and the feed conversion ratio (FCR) was
calculated. At 14 days of age, ileal samples were collected and used for
intestinal cytokine, TJ protein, and mucin gene expression analysis using qRT
PCR. The chickens supplemented with antibiotic (BMD) and B. subtilis strain 1781
alone (PB1) had significantly higher body weights compared to controls of the
same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2,
PB3) significantly improved the feed efficiency as evidenced by decreased FCR
compared to controls. No differences were observed in the expression of IL1beta,
IL17F, IFNgamma, and MUC2 gene among the different treatment groups. However,
elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2), and TNFSF15 (PB1, PB2,
PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was
upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1
group. IL13 was elevated in all probiotic-fed groups (PB1, PB2, PB3). Probiotic
supplementation was also shown to significantly increase the expression of TJ
proteins JAM2, ZO1 (PB2, PB3), and occludin (PB1, PB2). Taken together, B.
subtilis supplementation altered intestinal immune activity and influenced gut
barrier integrity through increased tight junction gene expression.
PMID- 28421425
TI - The Role of Alaska's Tribal Health Workers in Supporting Families.
AB - Alaska's Community Health Aides/Practitioners (CHA/Ps) are often the sole medical
workers in their communities in rural Alaska, and are instrumental in providing
healthcare services and education to otherwise underserved individuals. This
qualitative study explored how CHA/Ps support healthy families. Six CHA/Ps from
two rural communities in western Alaska were interviewed about their scope of
practice, interactions with mothers, infants, families, and teens, relationship
to other medical providers, and perceptions of their work. Using grounded theory,
verbatim notes were analyzed in Dedoose software and coded by thematic and
structural components. Interviewed CHA/Ps shared how the CHA/P program is a
culturally relevant way to deliver healthcare, and talked about the challenges of
the work, rewards, and suggestions for improvement. CHA/Ps described their unique
role as the on-the-ground health and wellness resource in their communities, and
talked about consulting with other medical professionals to provide better care
for individuals in rural Alaska. CHA/Ps described that they provided prenatal
care, patient education during pregnancy, emergency delivery services when
necessary, well-child visits, and outreach to teens to give fluoride rinses,
vaccinations, and education about issues such as sexual health and drugs/alcohol.
CHA/Ps also talked about patient education as a primary responsibility, which
also reduced patient load and prevented burn-out. The CHA/P program is a
comprehensive and innovative approach to providing healthcare education and
services that promotes healthy communities, including positive parent-infant
interactions, child wellness, and teen decision-making. The program is a
healthcare delivery model translatable to other tribal and limited-resource
contexts.
PMID- 28421426
TI - Decision-Making Preferences Among Older Hispanics Participating in a Colorectal
Cancer (CRC) Screening Program.
AB - Shared decision making has been shown to improve patients experience and
satisfaction with care within the health care setting but it is not clear that
all patients want to play an active role in health care decisions. The aim of
this study is to describe general decision control preferences among a
predominantly Spanish speaking Hispanic population. This is a cross-sectional
study using the Control Preference Scale to assess decision-making preference. A
total of 780 subjects completed the survey (response rate 89.9%). The majority
preferred a collaborative role (53.3%) compared to a passive (26.4%) or active
role (20.3%). We observed that individuals who were married or living with a
partner were more likely to prefer an active or collaborative role than their
unmarried counterparts (RRR 1.78 P value 0.017; RRR 1.56 p value 0.012). Less
acculturated individuals (i.e. more Spanish speaking at home were less likely to
prefer an active vs. passive role) (RRR 0.296, P value 0.029). Our predominantly
Spanish speaking Hispanic population showed a preference for collaborative versus
active or passive roles. There are several demographic factors that are
associated with this preference but it remains important to determine
individual's preference for decision making in health care settings.
PMID- 28421427
TI - Community Violence Exposure and Risk Taking Behaviors Among Black Emerging
Adults: A Systematic Review.
AB - Black emerging adults ages 18-29, particularly those residing in predominantly
black urban communities, are at risk for community violence exposure (CVE). This
potentially traumatic event may induce traumatic stress reactions for black
emerging adults that contribute to their engagement in violence perpetration,
substance use and/or sexual risk-taking behaviors as a way to cope with their
experiences. To address these identified concerns and make recommendations for
future research, this article identifies and synthesizes results from studies
that have examined CVE and its association with violence perpetration, substance
use, and sexual risk-taking behaviors among black emerging adults. We use the
term "black" throughout the article to refer to a socially constructed racial
group or identity and recognize that this group, like all other racial groups in
the United States, are ethnically heterogeneous. A systematic review of the
literature was conducted to identify studies that (1) included a measure of CVE
(2) included a measure of violence perpetration, substance use, or sexual risk
taking behaviors, and (3) included primarily black emerging adults. Results
showed CVE rates as high as 83% for black emerging adults. CVE was significantly
associated with substance use, but findings on the association of CVE with
violence perpetration and sexual risk-taking behaviors were mixed. Also, there
was a lack of consistency in measures used to assess CVE, suggesting that future
research should seek to identify "gold standard" measures and consider whether
they have been examined with black emerging adults or similar populations and
whether they capture the experiences of this unique population. Furthermore,
studies investigating factors that might moderate and/or mediate the relationship
between CVE, violence perpetration, substance use, and sexual risk-taking
behaviors among black emerging adults are warranted.
PMID- 28421428
TI - How Has CDER Prepared for the Nano Revolution? A Review of Risk Assessment,
Regulatory Research, and Guidance Activities.
AB - The Nanotechnology Risk Assessment Working Group in the Center for Drug
Evaluation and Research (CDER) within the United States Food and Drug
Administration (FDA) was established to assess the potential impact of
nanotechnology on drug products. One of the working group's major initiatives has
been to conduct a comprehensive risk management exercise regarding the potential
impact of nanomaterial pharmaceutical ingredients and excipients on drug product
quality, safety, and efficacy. This exercise concluded that current review
practices and regulatory guidance are capable of detecting and managing the
potential risks to quality, safety, and efficacy when a drug product incorporates
a nanomaterial. However, three risk management areas were identified for
continued focus during the review of drug products containing nanomaterials: (1)
the understanding of how to perform the characterization of nanomaterial
properties and the analytical methods used for this characterization, (2) the
adequacy of in vitro tests to evaluate drug product performance for drug products
containing nanomaterials, and (3) the understanding of properties arising from
nanomaterials that may result in different toxicity and biodistribution profiles
for drug products containing nanomaterials. CDER continues to actively track the
incorporation of nanomaterials in drug products and the methodologies used to
characterize them, in order to continuously improve the readiness of our science-
and risk-based review approaches. In parallel to the risk management exercise,
CDER has also been supporting regulatory research in the area of nanotechnology,
specifically focused on characterization, safety, and equivalence (between
reference and new product) considerations. This article provides a comprehensive
summary of regulatory and research efforts supported by CDER in the area of drug
products containing nanomaterials and other activities supporting the development
of this emerging technology.
PMID- 28421429
TI - Reslizumab in Eosinophilic Asthma: A Review.
AB - Reslizumab (Cinqaero(r); Cinqair(r)) is a humanized monoclonal antibody against
interleukin-5 (IL-5), a cytokine mediator of eosinophilic airway inflammation.
Reslizumab is indicated as an add-on treatment for severe eosinophilic asthma in
adults, on the basis of data from the BREATH phase III clinical trial programme.
In three double-blind BREATH studies of up to 52 weeks' duration, adding
intravenous reslizumab (3 mg/kg, once every 4 weeks) to the current asthma
therapy of patients (aged 12-75 years) with eosinophilic asthma inadequately
controlled with inhaled corticosteroids resulted in significant reductions in
clinical asthma exacerbation frequency and significant improvements in lung
function, asthma control and health-related quality of life relative to adding
placebo. Pooled data from the two trials of 52 weeks' duration indicated similar
benefits with reslizumab across various patient subgroups, including patients
with severe eosinophilic asthma. Reslizumab was generally well tolerated, with
very few recipients experiencing severe or serious treatment-related adverse
events. Moreover, in an open-label extension study, continued use of reslizumab
for up to 2 years was associated with durable lung function benefit, without any
new tolerability concerns. Thus, intravenous reslizumab extends the valuable add
on treatment options for adults with severe eosinophilic asthma inadequately
controlled with standard therapies.
PMID- 28421430
TI - Imbalance of morphofunctional responses of Jurkat T lymphoblasts at short-term
culturing with relief zinc- or copper-containing calcium phosphate coating on
titanium.
AB - Morphofunctional response of Jurkat T cells that were cultured for 24 h on
substrates prepared from commercially pure titanium with relief microarc
bilateral calcium phosphate coating containing copper or zinc was studied.
Changes in the concentration of essential trace elements contained in this
coating can cause significant imbalance of molecular processes of
differentiation, secretion, apoptosis, and necrosis and reduce tumor cell
survival.
PMID- 28421431
TI - Detection of autoantibodies to potentially amyloidogenic protein, gamma
synuclein, in the serum of patients with amyotrophic lateral sclerosis and
cerebral circulatory disorders.
AB - In this study, we analyzed serum for the presence of antibodies to gamma
synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the
control group of patients with other neurological diseases and healthy control
donors. As a result, antibodies against gamma-synuclein are not an ALS-specific
feature and have been identified in patients with ALS as well as in the control
group patients. Patients with the impaired cerebral circulation showed increased
incidence of autoantibodies to gamma-synuclein, yet the difference lacks
statistical representativeness due to limited sample size.
PMID- 28421432
TI - Regeneration of jejunal wall defect using an implant based on silk fibroin
fibers.
AB - Regenerative properties of fibroin implant vitalized with allogeneic bone marrow
cells were assessed. The study was performed using the experimental model of rat
jejunum wall damage. Three weeks after surgery, we observed recovery of all
layers of the jejunum wall at the site of injury and complete degradation of the
implant material.
PMID- 28421433
TI - Modification of the catalytic subunit of plasma fibrin-stabilizing factor under
induced oxidation.
AB - For the first time, by using mass-spectrometry method, the oxidation-mediated
modification of the catalytic FXIII-A subunit of plasma fibrin-stabilizing
factor, pFXIII, has been studied. The oxidative sites were identified to belong
to all structural elements of the catalytic subunit: the beta-sandwich (Tyr104,
Tyr117, and Cys153), the catalytic core domain (Met160, Trp165, Met266, Cys328,
Asp352, Pro387, Arg409, Cys410, Tyr442, Met475, Met476, Tyr482, and Met500), the
beta-barrel 1 (Met596), and the beta-barrel 2 (Met647, Pro676, Trp692, Cys696,
and Met710), which correspond to 3.9%, 1.11%, 0.7%, and 3.2%, respectively, of
oxidative modifications as compared to the detectable amounts of amino acid
residues in each of the structural domains. Lack of information on some parts of
the molecule may be associated with the spatial unavailability of residues,
complicating analysis of the molecule. The absence of oxidative sites localized
within crucial areas of the structural domains may be brought about by both the
spatial inaccessibility of the oxidant to amino acid residues in the zymogen and
the screening effect of the regulatory FXIII-B subunit.
PMID- 28421434
TI - Estimation of fluorescence lifetime of lipofuscin fluorophores contained in
lipofuscin granules of retinal pigment epithelium of human cadaver eyes without
signs of pathology.
AB - The fluorescence lifetimes of lipofuscin fluorophores contained in chloroform
extracts from retinal pigment epithelium (RPE) of human cadaver eyes without
signs of pathology were evaluated by single photon counting. The comparison of
fluorescence lifetimes of N-retinylidene-N-retinylethanolamine (A2E) and its
photooxidation and photodegradation products has been carried out. It was shown
that the contribution of A2E to the total fluorescence of chloroform extract from
lipofuscin granules is not major. The results are important for the improvement
of noninvasive diagnostic method of degenerative diseases of the retina and RPE
fundus autofluorescence (FAF).
PMID- 28421435
TI - Seasonal changes in proteolytic activity of calpains in striated muscles of long
tailed ground squirrel Spermophilus undulatus.
AB - Seasonal changes in proteolytic activity and content of calpains in striated
muscles of the longtailed ground squirrel Spermophilus undulatus were studied by
casein zymography and Western blotting analysis. The results testify to
hyperactivation of calpain proteases in the skeletal muscles of awakened animals
during the "winter" activity. The observed changes are discussed in the context
of adaptation of skeletal muscles of long-tailed ground squirrels to hibernation.
PMID- 28421436
TI - Molecular mechanisms of synthesis of noradrenaline as an inducer of development
in the adrenal glands of rats in ontogenesis.
AB - The level of gene expression and the protein content of tyrosine hydroxylase and
dopamine beta-hydroxylase were determined. In the perinatal period of rats, when
noradrenaline functions as a morphogenetic factor, the level of gene expression
of these enzymes increased and the content of protein products of these genes was
almost unchanged, indicating the difference in the regulatory mechanisms of their
transcription and translation.
PMID- 28421437
TI - Bioluminescent assay for toxicological assessment of nanomaterials.
AB - A new method for assessing biotoxicity of nanomaterials, based on the use of
soluble bioluminescent coupled enzyme system NAD(P)?H:FMN oxidoreductase and
luciferase, is proposed. The results of this study indicate a significant adverse
biological effect exerted by nanoparticles at the molecular level. It was found
that the most toxic nanoparticles the nanoparticles are based on copper and
copper oxide, as well as single-walled carbon nanotubes and multi-walled carbon
nanofibers, which are referred to hazard class II.
PMID- 28421438
TI - Analysis of fatty acid composition revealed differences in the diets of tadpoles
of two amphibian species.
AB - The study of the composition of fatty acid markers of tadpoles of cohabiting
amphibian species for the first time revealed differences in their diets: the
moor frog Rana arvalis prefers bacteria not associated with plant detritus,
whereas the diet of the common spadefoot Pelobates fuscus is based on
cyanobacteria, green algae, diatoms, and possibly higher plants. Major
differences in the fatty acid composition are determined by the difference in the
percentage of eicosapentaenoic and myristic acids.
PMID- 28421439
TI - Sigma-1 receptor antagonist haloperidol attenuates Ca2+ responses induced by
glutoxim and molixan in macrophages.
AB - Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1
receptor antagonist, antipsychotic haloperidol, significantly inhibits glutoxim-
and molixan-induced Ca2+-response in peritoneal macrophages. These results
indicate possible involvement of sigma-1 receptors in the signal cascade induced
by glutoxim or molixan and leading to intracellular Ca2+ concentration increase
in macrophages.
PMID- 28421440
TI - Transcriptomic changes in human umbilical cord blood endothelial cells under
simulated microgravity.
AB - Microarray analysis of cultured endothelial cells was performed 24 h after
simulated microgravity. A significant change in the expression of 177 genes that
can be classified into several functional clusters was detected. Among the genes
with overexpression, clusters of cell response to external stimuli and regulation
of cell motility and proliferation can be reliably distinguished. Among down
regulated genes, clusters of transcription factors with the "zinc fingers" domain
and factors involved in the regulation of morphogenesis and angiogenesis were
distinguished. The overlapping of signaling pathways involved in
mechanotransduction and inflammatory changes is discussed.
PMID- 28421441
TI - N-methyl serotonin analogues from the Bufo bufo toad venom interact efficiently
with the alpha7 nicotinic acetylcholine receptors.
AB - Two low-molecular-weight compounds were isolated from the parotid gland secret of
the toad Bufo bufo, which by absorption spectra and HPLC-MS/MS chromatography
data correspond to di- and trimethyl derivatives of serotonin (5
hydorxytryptamine): bufotenine (confirmed by counter synthesis) and bufotenidine
(5-HTQ). In experiments on competitive radioligand binding, these compounds
showed a higher affinity and selectivity for neuronal alpha7 nicotinic
acetylcholine receptors compared with the muscular cholinergic receptors. The
most efficient compound in terms of binding value was bufotenine, the efficiency
of 5-HTQ was an order of magnitude lower, and the minimal activity was exhibited
by serotonin.
PMID- 28421442
TI - Silica-containing inclusions in the cytoplasm of diatom Synedra acus.
AB - Cells of the araphid pennate diatom Synedra acus subsp. radians contain large
inclusion (1-15 MUm) storing silica, as revealed by transmission electron
microscopy and EDX-analysis. The size of the inclusions increases with the time
of cultivation of diatoms. Approximate concentration of SiO2 in the inclusions is
1-4%. It is assumed that silica in the inclusions is present as gelatinized
silica-gel. These results explain the possible mechanism of transport of silicic
acid into the cell against the concentration gradient.
PMID- 28421443
TI - Genomic mapping of chromatin proteins by using Daminv modification of an FLP
dependent DamID approach.
AB - To identify interactions of chromatin proteins with the genome of the cell type
of interest that is a part of heterologous tissues and organs of Drosophila, an
FLP-dependent DamID approach was recently developed [4], which does not require
sorting of cells or nuclei. Here, a modification of this approach, Daminv, is
described. The modified approach was validated by generating the binding pattern
of the LAM protein, a component of the inner membrane of the nuclear envelope,
with the genome of glial cells of the Drosophila larval central brains.
PMID- 28421444
TI - Long-term hyperthermia impairs activity of both photosystems.
AB - This is the first study to perform a simultaneous analysis of the activity of
photosystem 1 and photosystem 2 after long-term exposure to elevated temperature.
It was found that the quantum yield of photochemical reactions decreases in both
photosystems. It is shown that, in photosystem 2, the regulated nonphotochemical
quenching decreases whereas the unregulated non-photochemical quenching
increases. In photosystem 1, limitation on both acceptor and donor sides
increases.
PMID- 28421445
TI - Characterization of new modular nanotransporters with albumin-binding domain.
AB - The albumin-binding domain (ABD) with a site for its cleavage by tumor proteases
was inserted in the structure of modular nanotransporters (MNTs), chimeric
proteins for the delivery of anticancer drugs into the nuclei of cancer cells.
The effectiveness of this cleavage was tested in both variants of created
construct: "pure" ABD-MNT and the complex with albumin. The introduction of the
ABD module into MNTs had no effect on the binding of MNT with receptors on the
surface of the target cancer cells and on the preferential accumulation of MNTs
in the nuclei of these cells. The use of thermophoresis allowed us to determine
the equilibrium dissociation constants of the ABD-MNT complex with bovine and
human serum albumins.
PMID- 28421446
TI - PRE/TRE elements act as transcription activators in Drosophila S2 Cells.
AB - The Drosophila PRE/TRE elements are DNA targets for Polycomb and Trithorax group
proteins, which control repression and activation of gene transcription,
respectively. In this study, we show that, in transiently transfected Drosophila
S2 cells, bxdPRE activates transcription driven from different promoters. Using
CG32795 gene promoter, we demonstrate that other PRE/TRE elements-Fab7, en, eve,
and CycB-also act as transcription activators in this model system.
PMID- 28421447
TI - Inhibition of P-glycoprotein stimulates cell death under Hypoxia-mimicking
conditions.
AB - The most common drug resistance mechanism in tumor cells is expression on their
surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels
chemotherapeutic agents from the interior. An imitation of the hypoxic condition
by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF
1alpha) stabilization and inhibition of doxorubicin-induced apoptosis in colon
cancer NST116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation
leading to cell death induction. Considering these results, P-gp may be used as a
potential target to stimulate chemotherapeutic drugs activity that will
contribute to more efficient tumor cells elimination.
PMID- 28421448
TI - The bxdPRE/TRE element terminates passing through transcription.
AB - The regulation of PRE/TRE activity is required for appropriate tissue and stage
specific gene expression. However, the molecular principles of PRE/TRE activity
control remain unknown. Here we show that PRE/TRE element from Ubx regulatory
region efficiently terminates passing through transcription.
PMID- 28421449
TI - Flow cytometric analysis of the ERCC1, marker of DNA damage repair, in the tumor
specimens embedded into paraffin blocks.
AB - The differences in expression of ERCC1 were estimated between tumor specimens
embedded into paraffin blocks and surgical biopsy specimens of non-small cell
lung cancer as well as breast and ovarian cancers. Concordance or differences not
higher than 20% were observed in 73% of the cases. The number of the cases with
more significant differences in ERCC1 expression was less than 17%. The results
show that ERCC1 detection in surgical biopsy specimens by flow cytometry is the
more preferable method due to reduced preanalytical phase of the analysis.
PMID- 28421450
TI - The level of proapoptotic gene transcripts in wheat leaves under high temperature
stress.
AB - Under exposure of wheat plants to high temperatures (33, 37, and 43 degrees C),
the level of transcripts of the genes encoding proapoptotic proteins-TaMCAII
(encodes type II metacaspase) and TaBAX (functional homologue of the CDF1 gene of
Arabidopsis thaliana)-in leaf cells increased. This process at temperatures of 37
and 43 degrees C passed ahead of (in the case of TaBAX mRNA) or was accompanied
by (in the case of TaMCAII mRNA) the emergence of signs of nucleosomal DNA
degradation in leaves. The accumulation of malondialdehyde in the leaves of
seedlings exposed to temperatures of 37 and 43 degrees C coincided in time with a
change in the TaMCAII gene expression and the emergence of signs of programmed
cell death.
PMID- 28421451
TI - Mathematical model of polymerase chain reaction with temperature-dependent
parameters.
AB - The course of the real-time polymerase chain reaction (PCR) is determined by the
temperature dependence of the kinetics of the component reactions, particularly
the DNA strand hybridization. To investigate the effect of thermal processes on
the reaction behavior, a mathematical model in which the variable rate constant
of dissociation of "primer-single strand" complexes depends on temperature was
proposed. The reaction medium temperature, which depends on time, was also
introduced into the model. The proposed model of real-time PCR makes it possible
to analyze different aspects of the reaction, which are important for the
development of instruments and reagents for PCR.
PMID- 28421452
TI - Susceptibility of Candida albicans from Cystic Fibrosis Patients.
AB - Candida albicans is a common microbe, colonizer and potential pathogen found in
respiratory cultures of cystic fibrosis (CF) patients. Because of possible
development of resistance in patient isolates resulting from residence in the
abnormal milieu of CF patient airways, or from exposure to antifungals, and
considering the possibility of patient-to-patient spread of microbes and reports
of elevated resistance to other fungal pathogens, it was important to assay the
susceptibility of isolates of Candida and compare that profile to isolates from
the community. In our center, and unlike another fungal pathogen, no increase in
resistance of Candida isolates of the CF cohort was found.
PMID- 28421453
TI - Psychological Determinants of Medication Adherence in Stroke Survivors: a
Systematic Review of Observational Studies.
AB - BACKGROUND: Medications targeting stroke risk factors have shown good efficacy,
yet adherence is suboptimal. To improve adherence, its determinants must be
understood. To date, no systematic review has mapped identified determinants into
the Theoretical Domains Framework (TDF) in order to establish a more complete
understanding of medication adherence. PURPOSE: The aim of this study was to
identify psychological determinants that most influence stroke survivors'
medication adherence. METHODS: In line with the prospectively registered protocol
(PROSPERO CRD42015016222), five electronic databases were searched (1953-2015).
Hand searches of included full text references were undertaken. Two reviewers
conducted screening, data extraction and quality assessment. Determinants were
mapped into the TDF. RESULTS: Of 32,825 articles, 12 fulfilled selection criteria
(N = 43,984 stroke survivors). Tested determinants mapped into 8/14 TDF domains.
Studies were too heterogeneous for meta-analysis. Three TDF domains appeared most
influential. Negative emotions ('Emotions' domain) such as anxiety and concerns
about medications ('Beliefs about Consequences' domain) were associated with
reduced adherence. Increased adherence was associated with better knowledge of
medications ('Knowledge' domain) and stronger beliefs about medication necessity
('Beliefs about Consequences' domain). Study quality varied, often lacking
information on sample size calculations. CONCLUSIONS: This review provides
foundations for evidence-based intervention design by establishing psychological
determinants most influential in stroke survivors' medication adherence. Six TDF
domains do not appear to have been tested, possibly representing gaps in research
design. Future research should standardise and clearly report determinant and
medication adherence measurement to facilitate meta-analysis. The range of
determinants explored should be broadened to enable more complete understanding
of stroke survivors' medication adherence.
PMID- 28421454
TI - Quality Indicators in Endoscopic Ablation for Barrett's Esophagus.
AB - OPINION STATEMENT: Barrett's esophagus (BE) is a well-established premalignant
condition for esophageal adenocarcinoma (EAC); a cancer that is associated with a
poor 5-year survival rate. Several strategies have been explored in the context
of reducing the burden of EAC. Endoscopic eradication therapy (EET) is considered
the standard of care for the management of patients with BE with dysplasia and
early neoplasia; a practice that has been endorsed by all gastroenterology
societal guidelines. The effectiveness of EET has been demonstrated in multiple
studies and contemporary management includes a combination of endoscopic mucosal
resection (EMR) of all visible lesions followed by eradication of the remaining
BE using ablative techniques of which radiofrequency ablation (RFA) has the best
evidence supporting effectiveness and safety. These techniques are being used
increasingly at academic tertiary care centers and community practices. In this
era of value-based health care, there is increased focus on the establishment,
documentation, and reporting of quality indicators; indicators that are important
to physicians, patients, and payers. The purpose of this review is to highlight
the current status of quality indicators in EET for the management of patients
with BE-related neoplasia and discuss the future steps required to ensure that
these quality indicators are uniformly incorporated into practice.
PMID- 28421455
TI - Erratum to: Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the
Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double
Blind, Vehicle-Controlled Trial.
PMID- 28421456
TI - Filling the Void: A Review of Intragastric Balloons for Obesity.
AB - Endoscopic bariatric therapies are predicted to become much more widely used in
North America for obese patients who are not candidates for bariatric surgery. Of
all the endoscopic bariatric therapies, intragastric balloons (IGBs) have the
greatest amount of clinical experience and published data supporting their use.
Three IGBs are FDA approved and are now commercially available in the USA
(Orbera, ReShape Duo, and Obalon) with others likely soon to follow. They are
generally indicated for patients whose BMI ranges from 30 to 40 mg/kg2 and who
have failed to lose weight with diet and exercise. IGBs have been shown to be
safe, effective, and relatively straightforward to place and remove.
Accommodative symptoms commonly occur within the initial weeks post-placement;
however, major complications are rare. Gastric ulceration can occur in up to 10%
of patients, while balloon deflation with migration and bowel obstruction occurs
in <1% of patients. The effectiveness of the Orbera and ReShape Duo IGBs ranges
from 25 to 50% EWL (excess weight loss) after 6 months of therapy. The use of
IGBs is likely to grow dramatically in the USA, and gastroenterologists and
endoscopists should be familiar with their indications/contraindications,
efficacy, placement/removal, and complications.
PMID- 28421457
TI - KLF15 Inhibits Cell Proliferation in Gastric Cancer Cells via Up-Regulating
CDKN1A/p21 and CDKN1C/p57 Expression.
AB - BACKGROUND: Kruppel-like factors (KLFs) have been identified in multi-cancers and
act as oncogenes or tumor suppressors. The function of KLF15, one member of KLFs,
has not been well elucidated, especially in gastric cancer (GC). AIMS: This study
was designed to investigate the prognostic value and biological functions of
KLF15 in GC. METHODS: KLF15 protein expression in GC patients was evaluated by
immunohistochemistry assays in 50 paired GC tissues and adjacent normal tissues,
and correlations between KLF15 expression and clinicopathological characteristics
and prognosis were analyzed. Then, we investigated the over-expression of KLF15
on cell proliferation and its mechanism in GC cells. RESULTS: KLF15 expression
levels were significantly down-regulated in GC tissues compared to adjacent
normal tissues. And KLF15 expression was negatively correlated with clinical
stage, lymphatic metastasis, and distant metastasis. Furthermore, KLF15
expression could predict prognosis in patients with GC. Moreover, over-expression
of KLF15 could inhibit cell proliferation partly via regulating CDKN1A/p21 and
CDKN1C/p57. CONCLUSION: These findings demonstrate that KLF15 plays a significant
role in GC progression and could be a therapeutic target for GC.
PMID- 28421458
TI - Surgical Management of Pancreatic Cysts: A Shifting Paradigm Toward Selective
Resection.
AB - Due to the widespread use of high-quality cross-sectional imaging, pancreatic
cystic neoplasms are being diagnosed with increasing frequency. Clinicians are
therefore asked to counsel a growing number of patients with pancreatic cysts
diagnosed incidentally at an early, asymptomatic stage. Over the last two
decades, accumulating knowledge on the biologic behavior of these neoplasms along
with improved diagnostics through imaging and endoscopic cyst fluid analysis have
allowed for a selective therapeutic approach toward these neoplasms. On one end
of the management spectrum, observation is recommended for typically benign
lesions (serous cystadenoma), and on the other end, upfront resection is
recommended for likely malignant lesions (main duct IPMN, mucinous cystadenoma,
solid pseudopapillary tumor, and cystic pancreatic neuroendocrine tumors). In
between, management of premalignant lesions (branch duct IPMN) is dictated by the
presence of high-risk features. In general, resection should be considered
whenever the risk of malignancy is higher than the risk of the operation. This
review aims to describe the evolution and current status of evidence guiding the
selection of patients with pancreatic cystic neoplasms for surgical resection,
along with a specific discussion on the type of resection required and expected
outcomes.
PMID- 28421459
TI - Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a
genome-wide analysis.
AB - According to the recently updated World Health Organization (WHO) classification
(2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant
groups, the latter being significantly less aggressive in terms of both
progression-free and total survival. We identified a small cohort of WHO grade II
III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both
immunohistochemistry and molecular sequence analysis, which nonetheless had
unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among
these four cases, the mean time to recurrence as glioblastoma was only 16 months
and the mean total survival among the three patients who have died during the
follow-up was only 31 months. We hypothesized that these tumors had other,
unfavorable genetic or epigenetic alterations that negated the favorable effect
of the IDH mutation. We applied genome-wide profiling with a methylation array
(Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic
alterations in these tumors. As expected, the methylation profiles of all four
tumors were found to match most closely with IDH-mutant astrocytomas. Compared
with a control group of four indolent, age-similar WHO grade II-III astrocytomas,
the tumors showed markedly increased levels of overall copy number changes, but
no consistent specific genetic alterations were seen across all of the tumors.
While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a
subset may rapidly recur and progress to glioblastoma. The precise underlying
cause of the increased aggressiveness in these gliomas remains unknown, although
it may be associated with increased genomic instability.
PMID- 28421460
TI - Flow arrest intra-arterial delivery of small TAT-decorated and neutral micelles
to gliomas.
AB - The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide
derived from human immunodeficiency virus-1. It has been used to facilitate
macromolecule delivery to various cell types. This cationic peptide is capable of
crossing the blood-brain barrier and therefore might be useful for enhancing the
delivery of drugs that target brain tumors. Here we test the efficiency with
which relatively small (20 nm) micelles can be delivered by an intra-arterial
route specifically to gliomas. Utilizing the well-established method of flow
arrest intra-arterial injection we compared the degree of brain tumor deposition
of cationic TAT-decorated micelles versus neutral micelles. Our in vivo and post
mortem analyses confirm glioma-specific deposition of both TAT-decorated and
neutral micelles. Increased tumor deposition conferred by the positive charge on
the TAT-decorated micelles was modest. Computational modeling suggested a
decreased relevance of particle charge at the small sizes tested but not for
larger particles. We conclude that continued optimization of micelles may
represent a viable strategy for targeting brain tumors after intra-arterial
injection. Particle size and charge are important to consider during the directed
development of nanoparticles for intra-arterial delivery to brain tumors.
PMID- 28421461
TI - The role of tumor board conferences in neuro-oncology: a nationwide provider
survey.
AB - The tumor board or multidisciplinary cancer meeting (MCM) is the foundation of
high value multidisciplinary oncology care, coordinating teams of specialists.
Little is known on how these meetings are implemented in Neuro-oncology. Benefits
of MCMs include coordination, direction for complicated cases, education, and a
forum for communication, emerging technology, and clinical trials. This study
identifies participation and utilization of neuro-oncology MCMs. A cross
sectional descriptive survey was dispersed through an internet questionnaire. The
Society of Neuro-Oncology and the American Brain Tumor Association provided a
list of dedicated neuro-oncology centers. All National Cancer Institute
designated centers, and participants in the Adult Brain Tumor Consortium or the
Brain Tumor Trials Collaborative were included, identifying 85 centers.
Discussion included primary brain tumors (100%), challenging cases (98%),
recurrent disease (96%), neoplastic spine disease (93%), metastatic brain lesions
(89%), pre-surgical cases (82%), pathology (76%), and paraneoplastic disease
(40%). MCMs were composed of neuro-oncologists, neurosurgeons, and radiation
oncologists (100%), radiologists (98%), pathologists (96%), and clinical trial
participants (64%). Individual preparation ranged from 15 to 300 min. MCMs were
valued for clinical decision making (94%), education (89%), and access to
clinical trials (69%). 13% documented MCMs in the medical record. 38% of centers
used a molecular tumor board; however, many commented with uncertainty as to how
this is defined. Neuro-oncology MCMs at leading U.S. institutions demonstrate
congruity of core disciplines, cases discussed, and perceived value. We
identified variability in preparation time and implementation of MCM
recommendations. There is high uncertainty as to the definition and application
of a molecular tumor board.
PMID- 28421462
TI - Molecular alterations in pediatric gliomatosis cerebri are similar to those in
less invasive forms of pediatric diffuse glioma.
PMID- 28421463
TI - ZEB1 expression in Chinese lower-grade gliomas.
PMID- 28421464
TI - A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive
Adrenocortical Carcinoma.
AB - Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations
mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT)
transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to
poorer outcomes in other malignancies, but their role in ACC is unknown. We
describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at
age 76. After primary tumor resection, mitotane therapy was started as palliation
to low-volume liver metastasis. After a 2-year period of stable disease, the
patient died due to brain metastasis. Somatic gene sequencing revealed a novel
TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp
in exon 8 (c.811_818del8; GAGGTGCG/-) in homo or hemizygosis causing a subsequent
frameshift and premature stop codon at position 302. Immunohistochemistry of P53
and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical
analysis showed an increased expression of the mesenchymal markers vimentin and
fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also
overexpressed in tumoral cells. This case report describes an aggressive ACC with
not only a novel somatic mutation, but also a novel International Agency for
Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the
expression of EMT inducers TWIST1 and SIP1 have been reported for the first time
in an ACC case. Further investigation is needed to clarify the biologic
significance of this new TP53 mutation and its role in the EMT process.
PMID- 28421465
TI - The Role of the Molecular Clock in Skeletal Muscle and What It Is Teaching Us
About Muscle-Bone Crosstalk.
AB - PURPOSE OF REVIEW: This review summarizes what has been learned about the
interaction between skeletal muscle and bone from mouse models in which BMAL1, a
core molecular clock protein has been deleted. Additionally, we highlight several
genes which change following loss of BMAL1. The protein products from these genes
are secreted from muscle and have a known effect on bone homeostasis. RECENT
FINDINGS: Circadian rhythms have been implicated in regulating systems
homeostasis through a series of transcriptional-translational feedback loops
termed the molecular clock. Recently, skeletal muscle-specific disruption of the
molecular clock has been shown to disrupt skeletal muscle metabolism.
Additionally, loss of circadian rhythms only in adult muscle has an effect on
other tissue systems including bone. Our finding that the expression of a subset
of skeletal muscle-secreted proteins changes following BMAL1 knockout combined
with the current knowledge of muscle-bone crosstalk suggests that skeletal muscle
circadian rhythms are important for maintenance of musculoskeletal homeostasis.
Future research on this topic may be important for understanding the role of the
skeletal muscle molecular clock in a number of diseases such as sarcopenia and
osteoporosis.
PMID- 28421467
TI - Coronary physiology revisited.
PMID- 28421466
TI - Parathyroid Diseases and T Cells.
AB - PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T
cells in the bone catabolic effects of hyperparathyroidism and parathyroid
hormone (PTH). RECENT FINDINGS: Work in animals combined with recent
translational studies in humans now highlight the potent amplificatory action of
T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a
complex pathway by which PTH exploits natural self-renewal functions of CD4+ T
cells, to drive TNFalpha production that promotes formation of IL-17A secreting
Th17 T cells. TNFalpha and IL-17 further amplify osteoblastic receptor activator
of NF-kappaB ligand (RANKL) production and down-modulate osteoprotegerin (OPG),
establishing conditions propitious for osteoclastic bone resorption. These
findings are consistent with, and add to, the traditional view of PTH-induced
bone loss involving only osteoblast-lineage cells. T cells potently amplify
traditional pathways and provide permissive costimulatory signals to bone marrow
stromal cells, facilitating the development of an increased RANKL/OPG ratio
favourable to bone resorption and bone loss.
PMID- 28421468
TI - Gambling in rhesus macaques (Macaca mulatta): The effect of cues signaling risky
choice outcomes.
AB - Preference for a larger-variable "risky" option over a smaller-reliable "safe"
option often depends upon the likelihood that the risky option will deliver a
sufficiently sized reward to have an equivalent or superior expected value.
However, preference for the risky option has been shown to increase under
conditions where informative stimuli signaling the outcome of a risky choice is
included between the choice and the outcome and this risk-prone preference
persists even when the risky option has a lower expected value than the
alternative safe option. In the present study, rhesus macaques chose between a
risky option and a safe option across two experimental phases to determine
whether the outcome signal affected the degree of preference for the risky
option. Overall, six out of seven macaques showed a greater preference for the
risky option in the signaled condition than in the unsignaled condition. The
macaques' risky choices were sensitive to the expected value of the risky option
and the signaled condition produced a general increase in risky choices
independently of the expected value of the risky outcome. Overall, these results
are consistent with those obtained with other animals, and this may relate to a
process where animals show a biased preference for "good news." This process may
model some of the relevant factors that explain the psychology of gambling in
humans.
PMID- 28421469
TI - Effectiveness and Safety of Different Once-Daily Doses of Adrenocorticotropic
Hormone for Infantile Spasms.
AB - INTRODUCTION: Adrenocorticotropic hormone (ACTH) has been commonly used as a
first-line treatment for infantile spasms (IS), but its optimal dose and duration
are still unclear. This study is the largest retrospective cohort to document the
therapeutic efficacy and tolerability for three gradient doses of ACTH in
IU/kg/day units in Chinese patients. OBJECTIVE: The aim of our study was to
elucidate the effectiveness and safety of three different low doses and duration
of ACTH treatment for IS in China. METHODS: We conducted a retrospective, chart
review of IS cases that were treated with biologic short-acting ACTH and followed
up for at least 6 months at a single center in China between June 2010 and June
2016. In total, 200 children met the inclusion criteria. Cases were divided into
three groups according to dosage (1, 1.1-1.9, and 2-4 IU/kg/day). Furthermore, we
divided the 2-4 IU/kg/day group into 2-3 and 3.1-4 IU/kg/day subgroups. All
groups were evaluated for response rates, relapse rates, and adverse effects.
RESULTS: Electroclinical remission by day 14 occurred in 41.4% of infants given 2
4 IU/kg/day and 36.4% of infants given 1.1-1.9 IU/kg/day, compared with only
14.7% of patients given 1 IU/kg/day (p = 0.004 and 0.03, respectively).
Prolonging ACTH treatment for up to 28 days improved response by 24% in all 200
infants. Overall, 73.9% of infants receiving 2-4 IU/kg/day responded,
significantly higher than the 52.7% responding to 1.1-1.9 IU/kg/day and the 23.5%
responding to 1 IU/kg/day (p < 0.01). There was no significant difference in the
number of relapses or adverse effects in the three groups. Moreover, in the 2-4
IU/kg/day group, 74.7% of children receiving 2-3 IU/kg/day of ACTH responded,
compared with 70% who responded to 3.1-4 IU/kg/day (p = 0.78). CONCLUSIONS: ACTH
at a dosage of 2-3 IU/kg/day is superior to 1.1-1.9 and 1 IU/kg/day dosages, is
as good as a 3.1-4 IU/kg/day dosage in terms of response rate, and causes no more
adverse effects or relapses than other dosages. In addition, prolonging the
duration of ACTH treatment can improve response.
PMID- 28421470
TI - Adrenalectomy: indications and options for treatment.
AB - The history of adrenal surgery is longstanding. Firstly described in 1889 by
Thornton, the open adrenalectomy has been for decades the only surgical approach
to adrenal diseases. Nowadays, instead, several approaches to adrenal glands have
been described in the literature, such as laparoscopic adrenalectomy, robotic
assisted procedure and single-incision technique. Actually, laparoscopic
adrenalectomy is considered as the gold standard treatment for adrenal lesions.
In fact, all functional tumors, including pheochromocytoma, are candidates for a
laparoscopic approach in the absence of other contraindications. In the adrenal
gland surgery, it is important to consider that a multidisciplinary approach
which comprises surgeons, anesthesiologists, endocrinologists, and oncologists
plays an important role in the management of patients and that the success of the
procedure is related also to surgeon experience and hospital volume. This review
aims to discuss the indications for adrenalectomy and to describe the different
techniques options for the adrenal gland surgery.
PMID- 28421471
TI - Social Marketing as a Framework for Youth Physical Activity Initiatives: a 10
Year Retrospective on the Legacy of CDC's VERB Campaign.
AB - PURPOSE OF REVIEW: In 2002, the U.S. Centers for Disease Control and Prevention
(CDC) launched the VERB. It's what you do! campaign to increase physical activity
among tweens and concomitantly respond to the rise in childhood obesity. This
retrospective study summarizes the history of the VERB campaign's social
marketing approach and its effectiveness in promoting behavior change in the
targeted population. RECENT FINDINGS: The legacy of VERB, which ended in 2006, is
discussed, with an emphasis on examining initiatives over the last decade and the
degree to which they followed (or did not follow) the structural and thematic
lead of the campaign. The article ends with suggestions for how VERB still has
the potential to inform other social marketing campaigns going forward.
PMID- 28421473
TI - Personality, emotion-related variables, and media pressure predict eating
disorders via disordered eating in Lebanese university students.
AB - PURPOSE: Disordered eating behaviors are on the rise among youth. The present
study investigates psychosocial and weight-related variables as predictors of
eating disorders (ED) through disordered eating (DE) dimensions (namely
restrained, external, and emotional eating) in Lebanese university students.
METHODS: The sample consisted of 244 undergraduates (143 female) aged from 18 to
31 years (M = 20.06; SD = 1.67). Using path analysis, two statistical models were
built separately with restrained and emotional eating as dependent variables, and
all possible direct and indirect pathways were tested for mediating effects. The
variables tested for were media influence, perfectionism, trait emotional
intelligence, and the Big Five dimensions. RESULTS: In the first model, media
pressure, self-control, and extraversion predicted eating disorders via emotional
eating. In the second model, media pressure and perfectionism predicted eating
disorders via restrained eating. DISCUSSION: Findings from this study provide an
understanding of the dynamics between DE, ED, and key personality, emotion
related, and social factors in youth. Lastly, implications and recommendations
for future studies are advanced.
PMID- 28421472
TI - Screen Time, Other Sedentary Behaviours, and Obesity Risk in Adults: A Review of
Reviews.
AB - PURPOSE OF REVIEW: The aim of this paper is to assess the association between
sedentary behaviours, including screen time, and risk of obesity in adults. A
review of 10 systematic reviews was undertaken. RECENT FINDINGS: Available
evidence is generally not supportive of associations between sedentary behaviour
and obesity in adults. Most studies that found significant associations indicated
mostly small effect sizes. Somewhat more consistent associations were shown for
screen time (mainly TV viewing), among older adults, and for pre-adult sedentary
behaviour to increase the risk of obesity in adulthood. Some evidence also exists
for breaks in sedentary time to be associated with a more favourable BMI, and for
use of a car to be associated with greater risk of obesity. There is limited
evidence for an association between sedentary behaviour in adulthood and obesity
and any association that exists does not seem to be causal. Future research is
required investigating potentially positive effects for frequent breaks from
sitting, less car use, and an uncoupling of TV viewing and dietary intake.
PMID- 28421474
TI - Social safeness and disordered eating: Exploring underlying mechanisms of body
appreciation and inflexible eating.
AB - Feelings of social safeness and connectedness have been associated with adaptive
emotion regulation processes and well-being indicators. Further, literature has
demonstrated that interpersonal experiences play an important role in the
etiology and maintenance of body and eating psychopathology. However, the study
of the role of social variables and emotion regulation processes in the
engagement in inflexible eating rules and eating psychopathology is still in its
early stages. The current study aims to fill some gaps within the literature and
explore the mediator role of body appreciation and inflexible eating rules in the
link between social safeness and disordered eating. Participants were 253 women,
aged between 18 and 50 years old, who completed a series of online self-report
measures. Results from the tested path analysis model showed that social safeness
holds a significant effect on eating psychopathology, through the mechanisms of
body appreciation and inflexible eating rules. Also, results suggested that women
who present higher levels of social safeness tend to present a more positive and
respectful attitude towards their body and decreased adoption of inflexible
eating rules, which seem to explain lower levels of disordered eating behaviours.
These findings seem to present empirical support for the development of
intervention programs that promote a positive, affectionate and healthy
relationship with one's body image, in order to prevent the inflexible adherence
to eating rules and disordered eating behaviours.
PMID- 28421476
TI - Academic Productivity in Psychiatry: Benchmarks for the H-Index.
AB - OBJECTIVE: Bibliometrics play an increasingly critical role in the assessment of
faculty for promotion and merit increases. Bibliometrics is the statistical
analysis of publications, aimed at evaluating their impact. The objective of this
study is to describe h-index and citation benchmarks in academic psychiatry.
METHODS: Faculty lists were acquired from online resources for all academic
departments of psychiatry listed as having residency training programs in Canada
(as of June 2016). Potential authors were then searched on Web of Science
(Thomson Reuters) for their corresponding h-index and total number of citations.
RESULTS: The sample included 1683 faculty members in academic psychiatry
departments. Restricted to those with a rank of assistant, associate, or full
professor resulted in 1601 faculty members (assistant = 911, associate = 387,
full = 303). h-index and total citations differed significantly by academic rank.
Both were highest in the full professor rank, followed by associate, then
assistant. The range in each, however, was large. CONCLUSIONS: This study
provides the initial benchmarks for the h-index and total citations in academic
psychiatry. Regardless of any controversies or criticisms of bibliometrics, they
are increasingly influencing promotion, merit increases, and grant support. As
such, benchmarking by specialties is needed in order to provide needed context.
PMID- 28421475
TI - Association of white and red meat consumption with general and abdominal obesity:
a cross-sectional study among a population of Iranian military families in 2016.
AB - PURPOSE: To assess the association of red and white meat consumption with general
and abdominal obesity among Iranian military families. METHODS: In this cross
sectional study, 525 subjects with age range of 19-55 years belong to military
families of Army of Islamic Republic of Iran were recruited during 2016. Dietary
data were collected using semi-quantitative food-frequency questionnaire. A self
reported questionnaire was used to collect data on demographic characteristics
and anthropometric measurements. General obesity was defined as body mass index
>=25 kg/m2 and abdominal obesity as waist circumference >=80 cm for women and >=
94 cm for men. Finally, we had complete data on 170 subjects for analysis.
RESULTS: Mean age of subjects was 33.78 +/- 6.48. We found a significant positive
association between red meat consumption and abdominal obesity in fully adjusted
model, so that subjects in the fourth quartile had 4.51 more odds to be
abdominally obese compared with those in the first quartile of red meat
consumption (OR 4.51, 95% CI 1.32-15.40). Such relationship was not seen for
general obesity. In addition, white meat consumption was not associated with
general and abdominal obesity either before or after adjustment for covariates.
CONCLUSIONS: Red meat consumption was positively associated with abdominal
obesity. No significant relationship was found between white meat consumption,
and general and abdominal obesity. Therefore, further studies are needed to shed
light our findings.
PMID- 28421477
TI - Collaborative Training Efforts with Pediatric Providers in Addressing Mental
Health Problems in Primary Care.
PMID- 28421478
TI - Facilitating the Feedback Process on a Clinical Clerkship Using a Smartphone
Application.
AB - OBJECTIVES: This pilot study evaluated the effects of a smartphone-triggered
method of feedback delivery on students' perceptions of the feedback process.
METHODS: An interactive electronic feedback form was made available to students
through a smartphone app. Students were asked to evaluate various aspects of the
feedback process. Responses from a previous year served as control. RESULTS: In
the first three quarters of academic year 2014-2015 (pre-implementation), only
65% of responders reported receiving oral feedback and 40% reported receiving
written feedback. During the pilot phase (transition), these increased to 80% for
both forms. Following full implementation in academic year 2015-2016 (post
implementation), 97% reported receiving oral feedback, and 92% reported receiving
written feedback. A statistically significant difference was noted pre- to post
implementation for both oral and written feedback (p < 0.01). A significant
increase from pre-implementation to transition was noted for written feedback (p
< 0.01) and from transition to post-implementation for oral feedback (p < 0.01).
Ninety-one and 94% of responders reported ease of access and timeliness of the
feedback, 75% perceived the quality of the feedback to be good to excellent; 64%
felt receiving feedback via the app improved their performance; 69% indicated the
feedback method as better compared to other methods. Students acknowledged the
facilitation of conversation with supervisors and the convenience of receiving
feedback, as well as the promptness with which feedback was provided. The use of
a drop-down menu was thought to limit the scope of conversation. CONCLUSION:
These data point to the effectiveness of this method to cue supervisors to
provide feedback to students.
PMID- 28421479
TI - Understanding Medical Students' Experience with Stress and Its Related
Constructs: A Focus Group Study from Singapore.
AB - OBJECTIVE: In order to protect medical students from burnout and its untoward
psychiatric effects, it is imperative to understand their stress, burnout,
coping, and resilience experiences. This study aimed to derive collective
definitions from the medical student perspective, to identify common themes of
students' experiences, and to distinguish pre-clinical and clinical year
students' experiences relating to these four constructs. METHODS: The authors
conducted focus groups of medical students in Singapore across 4 years using a
semi-structured question guide. Participants shared their understanding,
experiences, and the relationships between stress, burnout, coping, and
resilience. Coders independently evaluated construct definitions and derived
common themes through an iterative process, and compared transcripts of pre
clinical and clinical year students to determine differences in experience over
time. RESULTS: Nine focus groups (54 students, 28 females, mean age 24.3) were
conducted. Students identified common definitions for each construct. Nine themes
emerged within three domains: (1) relating constructs to personal experience, (2)
interrelating stress, burnout, coping, and resilience, and (3) understanding the
necessity of stress. Compared to clinical students, pre-clinical students
reported theory-based rather than reality-based experiences and exam-induced
stress, defined constructs using present rather than future situations, and
described constructs as independent rather than interrelated. CONCLUSIONS: This
sample of medical students in Singapore shares a common understanding of stress,
burnout, coping, and resilience, but experiences these uniquely. They perceive a
positive role for stress. These findings build upon prior literature, suggesting
an interrelationship between stress and its related constructs and adding the
novel perspective of students from an Asian country.
PMID- 28421480
TI - Amount of Sleep, Daytime Sleepiness, Hazardous Driving, and Quality of Life of
Second Year Medical Students.
AB - OBJECTIVE: The authors describe the sleep habits of second year medical students
and look for associations between reported sleep duration and depression,
burnout, overall quality of life, self-reported academic success, and falling
asleep while driving. METHODS: The authors conducted a cross-sectional
descriptive study of two consecutive cohorts of second year medical students at a
large public university in the USA. Participants completed an anonymous survey
about their sleep habits, daytime sleepiness (Epworth sleepiness scale), burnout
(Maslach burnout inventory), depression (PRIME MD), and perceived stress
(perceived stress scale). Categorical and continuous variables were compared
using chi square tests and t tests, respectively. RESULTS: Sixty-eight percent of
the students responded. Many (34.3%) reported fewer than 7 h of sleep on typical
weeknights, including 6.5% who typically sleep less than 6 h. Twenty-five
students (8.4%) reported nodding off while driving during the current academic
year. Low typical weeknight sleep (fewer than 6 h vs 6-6.9 h vs 7 or more hours)
was associated with (1) higher Epworth sleepiness scale scores, (2) nodding off
while driving, (3) symptoms of burnout or depression, (4) decreased satisfaction
with quality of life, and (5) lower perceived academic success (all p values
<=0.01). Students reporting under 6 h of sleep were four times more likely to nod
off while driving than those reporting 7 h or more. CONCLUSION: Educational,
behavioral, and curricular interventions should be explored to help pre-clinical
medical students obtain at least 7 h of sleep most on weeknights.
PMID- 28421482
TI - Cost-Effectiveness of Stereotactic Radiosurgery and Stereotactic Body Radiation
Therapy: a Critical Review.
AB - PURPOSE OF REVIEW: This review aims to summarize and appraise published cost
effectiveness studies on stereotactic radiosurgery (SRS) and stereotactic body
radiation therapy (SBRT). RECENT FINDINGS: We performed a Medline search of cost
effectiveness studies of SRS, SBRT, and other cancer treatment modalities such as
surgery and systemic therapy from 2006 to 2016. We included studies that used
both modeling and retrospective review techniques. We excluded studies of benign
disease. We defined a strategy whose incremental cost-effectiveness ratio (ICER)
is <=$50,000/quality-adjusted life year (QALY) as "clearly cost-effective," a
strategy whose ICER is <=$100,000/QALY as "probably cost-effective," and a
strategy <=$200,000/QALY as "possibly cost-effective." We appraised modeling
studies by determining whether or not they conform to the International Society
for Pharmacoeconomics and Outcomes Research Good Research Practices (ISPOR) in
modeling task force good research practices in model transparency and validation.
We identified 24 studies that met inclusion criteria. Treatment sites included
brain, bone, liver, lung, pancreas, and prostate. SRS and SBRT were clearly cost
effective strategies in 17 studies, probably cost-effective in 3 studies, and
possibly cost-effective in 2 studies. Of the 16 modeling studies,15 conformed to
transparency best practices; however, only 6 studies performed rigorous
validation as described by the ISPOR guidelines. CONCLUSIONS: SRS and SBRT are
likely to be cost-effective management strategies across a large variety of
treatment sites and techniques. However, rigorous model validation techniques are
lacking in these modeling studies.
PMID- 28421481
TI - Cancer as a Risk Factor for Cardiovascular Disease.
AB - Improvements in early diagnosis and cancer treatments have contributed to high
survival rates for many cancer patients. However, these patients often die of
cardiovascular disease rather than recurrence of their cancer. Heart disease
manifesting after cancer may be due to several mechanisms: shared cardiovascular
risks between cancer and cardiovascular disease, inflammatory states associated
with malignancies, and/or cardiotoxic effects of cancer therapy. Cancer treatment
increases the risk of cardiovascular diseases directly by damaging critical
structures of the heart or indirectly by promoting accelerated atherosclerosis.
Estimating cardiovascular risk by using advanced imaging and monitoring of the
cardiac biomarkers can be used for early detection and treatment of subclinical
cardiac injury. Better knowledge of these early and late cardiac effects in
cancer patients will enable adoption of both primary and secondary prevention
measures of long-term treatment complications in cancer survivors.
PMID- 28421483
TI - Update on Embolization Therapies for Hepatocellular Carcinoma.
AB - PURPOSE OF REVIEW: The purpose of the review is to summarize the latest
applications for embolotherapy in the management of patients with HCC according
to BCLC stage. RECENT FINDINGS: While traditionally reserved for patients with
unresectable HCC and stage B disease, there is an important role for embolization
therapies in earlier stage patients as an adjunct to ablation, bridging, or
downstaging therapy, as a means to improve safety of resection, and potentially
as an arterial ablative option in the case of radioembolization. Newer
applications of radioembolization such as radiation segmentectomy have the
potential to provide cure in localized unifocal disease, and transarterial
chemoembolization-portal vein embolization and radiation lobectomy may provide a
combination of treatment and future liver remnant hypertrophy for planned hepatic
resection. There is also an increasing role for embolization in the treatment of
stage C disease, and recent data suggest it can be used in combination with
sorafenib with the potential for survival benefit over sorafenib alone, even in
the case of portal vein tumor thrombus. Embolization therapies play an
increasingly important role in patients with BCLC stage A-C hepatocellular
carcinoma. While different therapies may be offered on a patient-specific basis,
there are limited prospective RCT data to support superiority of one technique
over another.
PMID- 28421485
TI - Chapter 1 Historical Background on Gamete and Embryo Cryopreservation.
AB - This chapter describes the development of the science of cryopreservation of
gametes and embryos of various species including human. It attempts to record in
brief the main contributions of workers in their attempts to cryopreserve gametes
and embryos. The initial difficulties faced and subsequent developments and
triumphs leading to present-day state of the art are given in a concise manner.
The main players and their contributions are mentioned and the authors' aim is to
do justice to them. This work also attempts to ensure that credit is correctly
attributed for significant advances in gamete and embryo cryopreservation. In
general this chapter has tried to describe the historical development of the
science of cryopreservation of gametes and embryos as accurately as possible
without bias or partiality.
PMID- 28421486
TI - Chapter 2 Utility of Animal Models for Human Ovarian Tissue Cryopreservation.
AB - Success in cryopreservation of ovarian tissue (OT) in animal models has led to
develop efficient cryo-technologies for human ovarian tissue. In this chapter,
cryopreservation protocols developed for animal experiments are described.
PMID- 28421484
TI - The Role of Biomarkers in Detection of Cardio-toxicity.
AB - The goal of this paper is to review the current literature on the role of
biomarkers in the detection and management of patients with cardio-oncologic
disease. The role of biomarker surveillance in patients with known cardiac
disease, as a result of chemotherapy or with the potential to develop cardio
toxicity, will be discussed. In addition, the studies surrounding sub-clinical
cardiac toxicity monitoring during therapy, identification of high-risk patients
prior to therapy, and tailoring oncologic therapies to potential biomarker risk
profiles are reviewed. Based on evidence, to date, troponin and natriuretic
peptides have the greatest potential to detect sub-clinical cardiac dysfunction
and even tailor therapy to prevent progression based on biomarker profiles.
Finally, future directions for potential utilization of novel biomarkers for the
improvement of care of patients in the field of cardio-oncology are discussed.
PMID- 28421487
TI - Chapter 3 Current Challenges in Immature Oocyte Cryopreservation.
AB - Current freezing technology, especially the vitrification method, has markedly
improved oocyte survival rate after warming, and the pregnancy rate is comparable
to that achieved with fresh oocytes. However, most groups report using oocytes
matured in vivo for vitrification. Although immature oocytes can be vitrified
successfully, clinical outcomes do not reach that of vitrification of matured
oocytes. The current literature suggests that oocytes should be vitrified at
mature metaphase II (M-II) stage following IVM rather than at the immature
germinal vesicle (GV) stage, because the potential for oocyte maturation is
reduced when vitrification is performed on immature oocytes at the GV stage.
PMID- 28421488
TI - Chapter 4 Role of Antioxidants and Antifreeze Proteins in
Cryopreservation/Vitrification.
AB - In recent years, supplementation of antioxidants and antifreeze proteins during
cryopreservation/vitrification has significantly improved the survival and
function of oocytes and ovarian tissues (OT) in animal models. In this chapter,
the experimental protocols for the use of antioxidants and antifreeze proteins in
cryopreservation/vitrification are described.
PMID- 28421489
TI - Chapter 5 Slow Freezing of Human Sperm.
AB - Cryopreservation of human spermatozoa is a highly efficient procedure for
managing male fertility, and much of its successful application seems to have a
crucial impact on the reproductive outcome of assisted reproduction technologies.
Here, we present, explain, and describe the slow freezing method for preserving
human spermatozoa, which is currently the most commonly used freezing technique
in most clinical andrology laboratories.
PMID- 28421490
TI - Chapter 6 Technology of Aseptic Cryoprotectant-Free Vitrification of Human ICSI
Spermatozoa.
AB - The aim of this chapter was to describe the standardized aseptic technology of
permeable cryoprotectant-free vitrification of human spermatozoa in capillaries
(for ICSI or IVF in microvolume). Spermatozoa, vitrified by this technology, are
free from seminal plasma owing to swim-up procedure preceding vitrification and
are free from permeable cryoprotectants. They are ready for further use
immediately after warming without any additional treatment.
PMID- 28421491
TI - Chapter 7 Human Epididymal and Testicular Sperm Cryopreservation.
AB - Since the advent of intracytoplasmic sperm injection (ICSI) in the early 1990s,
surgical techniques to recover samples from the epididymis and testis directly
have been used to benefit patients suffering from obstructive and nonobstructive
azoospermia. Various studies have demonstrated comparable fertilization, ongoing
pregnancy, and implantation rates when fresh and frozen-thawed epididymal sperms
were used for ICSI [1]. Injection of fresh and frozen testicular sperms into
mature oocytes resulted in similar fertilization rates in cases of obstructive
azoospermia. However, in cases of nonobstructive azoospermia, the outcome depends
upon the degree of impairment of spermatogenesis, criteria for sperm freezing,
and patient selection [2].
PMID- 28421492
TI - Chapter 8 Human Oocytes Slow-Rate Freezing: Methodology.
AB - Cryopreservation of human oocytes is an important technique for the treatment of
human infertility, as it deals successfully with legal, ethical, and moral issues
related to embryo cryopreservation (Coticchio et al., Human Fertil (Camb) 4:152
157, 2001; Tucker et al., Eur J Obstet Gynecol Reprod Biol 113: 524-527, 2004)
and maintains reproductive potential in women with diseases or conditions that
may compromise reproductive capacity. Here, we describe an oocyte
cryopreservation technique involving slow freezing-rapid thawing with
differential sucrose concentration (0.2 M in the freezing stage-0.3 M in thawing
stage) (Bianchi et al., Reprod Biomed Online. 14:64-71, 2007), describing the
technique in detail, from the preparation of the solutions through to the
performance of the technique and, finally, to a number of helpful hints for
optimum results.
PMID- 28421493
TI - Chapter 9 Slow Freezing and Thawing of Human Cleavage Stage Embryos.
AB - The ability to store human embryos in a viable state at very low temperatures has
been critical to the evolution of responsible practice in clinical Assisted
Reproductive Technology (ART). It has encouraged a reduction in the frequency of
simultaneous multiple embryo transfer and thereby reduced the risks associated
with multiple pregnancy while maintaining high cumulative pregnancy rates from
single oocyte collection cycles. In this chapter, we describe a simple slow
freezing procedure for human early cleavage stage embryos that results in a high
proportion of post-thaw embryos surviving and retaining their implantation
potential.
PMID- 28421494
TI - Chapter 10 Human Oocyte Vitrification.
AB - Discovery and widespread application of successful cryopreservation methods for
MII-phase oocytes was one of the greatest successes in human reproduction during
the past decade. Although considerable improvements in traditional slow-rate
freezing were also achieved, the real breakthrough was the result of introduction
of vitrification. Here we describe the method that is most commonly applied for
this purpose, provides consistent survival and in vitro developmental rates,
results in pregnancy and birth rates comparable to those achievable with fresh
oocytes, and does not result in higher incidence of gynecological or postnatal
complications.
PMID- 28421495
TI - Chapter 11 Human Embryo Vitrification.
AB - Cryopreservation is one of the keystones in clinical infertility treatment. In
particular vitrification has become a well-established and widely used routine
procedure that has allowed important expansion of therapeutic strategies when IVF
is used to treat infertility. Vitrification of human blastocysts allows us to
maximize the potential for conception from any single in vitro fertilization
cycle and prevents wastage of embryos. The technology may even be used to
eliminate fresh embryo transfers for reasons of convenience, uterine receptivity,
fertility preservation, preimplantation genetic diagnosis, or emergency
management. In this chapter, the application of vitrification technology for
cryopreserving human blastocysts will be revealed through step-by-step protocols.
The results that are presented using the described protocols underscore the
robustness of the vitrification technology for embryo cryopreservation.
PMID- 28421496
TI - Chapter 12 Human Ovarian Tissue Slow Freezing.
AB - Cryopreservation of human ovarian tissue is now being accepted as a mainstream
ART laboratory procedure. The procedure described has been validated for use at
the histological and functional level, and, recently, unequivocal evidence of
preservation of primordial follicles has been demonstrated following twin births
from cryopreserved ovarian tissue grafted at a heterotopic site.
PMID- 28421497
TI - Chapter 13 Human Ovarian Tissue Vitrification.
AB - Ovarian freezing and transplantation has garnered increasing interest as a
potential way of preserving fertility in cancer patients as well as for women who
just wish to delay childbearing. This chapter spells out our techniques of
ovarian cortex vitrification and results for frozen compared to fresh ovarian
cortex transplantation (in one single series from one center for the sake of
consistency), as well as potentially provides insight into the mechanism behind
ovarian follicle recruitment. This represents an effort to simplify and
popularize an approach that has yielded favorable results (all cases recovered
ovulation and 75% had successful spontaneous pregnancy) in one single,
disciplined study. It should be clear that this is a review for the more general
reader of our original scientific papers published in Reproductive BioMedicine
Online, New England Journal of Medicine, Fertility and Sterility, Human
Reproduction, Molecular Human Reproduction, and Journal of Assisted Reproduction
and Genetics (JARG).
PMID- 28421498
TI - Chapter 14 Establishing an Oocyte Cryobank Network.
AB - Improvements in oocyte cryopreservation has prompted wider acceptance of this
technology leading to its use for several reasons. Notably, in addition to
elective and medically driven reasons for oocyte cryostorage for fertility
preservation, donor oocyte cryobanking is beginning to gain traction, potentially
replacing fresh oocyte donation in assisted reproduction. Donor "egg banking,"
while not totally analogous to donor sperm banking, does provide strong benefits
in terms of scheduling flexibility and improved clinical efficiencies, while
providing a wider immediate inventory choice. The development of a successful
cryobank "network" and subsequent growth into a full-access donor egg bank are
only possible through adoption of a series of key steps involving establishment
of a repeatable vitrification protocol with a strong clinical record,
incorporation of a comprehensive database and quality management system, and
strict control over the logistics of inventory and shipping and receiving, to
establish a flawless chain from donor to recipient. Confidence will grow in this
potentially difficult process over time.
PMID- 28421499
TI - Chapter 15 Development of a Nationwide Network for Ovarian Tissue
Cryopreservation.
AB - Ovarian tissue cryopreservation is gaining much interest since the publication of
the first live birth after retransplantation of frozen-thawed tissue in 2004
(Donnez et al., Lancet 364:1405-1410, 2004). In contrast to cryopreservation of
gametes and embryos, ovarian tissue freezing is a complex requiring a proper
approach in order to make this a viable option for fertility preservation of
cancer patients. Due to the need in terms of laboratory space, equipment,
personnel, and adequate logistics, an ovarian tissue cryobank is most economic if
managed as a centralized service unit that interacts with numerous clinics
covering the surgical part. Transportation of ovarian tissue under appropriate
conditions from the surgical unit to the cryobank for subsequent preparation and
freezing has been shown to have no impact on cryo-survival (Schmidt et al., Hum
Reprod 18:2654-2659, 2003; Isachenko et al., Fertil Steril 91:1556-1559, 2009).
Several children have been born after retransplantation of such tissue that was
derived from the cryobank in Bonn, Germany (Homepage FertiPROTEKT.
http://www.fertiprotekt.de ). This cryobank is one of the largest in the world
with more than 1300 tissue samples that were frozen from 2003 until today. It is
integrated in the network FertiPROTEKT (Homepage FertiPROTEKT.
http://www.fertiprotekt.de ) and is served by 108 surgical centers that are
located all over Germany. The concept of this cryobank is a blueprint for success
and has recently been used for another regionally centralized cryobank in
Beijing, China. In this chapter the most important topics that need to be
considered while creating a centralized cryobank within a national or regional
network are highlighted.
PMID- 28421500
TI - Chapter 16 Directional Freezing of Ovarian Tissue and Freeze-Drying of Stem Cells
for Fertility Preservation.
AB - Fertility preservation is practiced today for women in their fertile years who
wish or need to postpone or prolong their reproductive era. Currently women have
two main options to preserve their fertility either by oocyte vitrification or by
freezing of ovarian cortical slices. In this chapter we will describe the use of
directional freezing for cortical slices and freeze-drying of stem cells. These
procedures open the way for the preservation of reproductive cells and tissue for
future use in fertility preservation treatments.
PMID- 28421501
TI - Chapter 17 Sterile Plate-Based Vitrification of Adherent Human Pluripotent Stem
Cells and Their Derivatives Using the TWIST Method.
AB - Due to their high biological complexity, e.g., their close cell-to-cell contacts,
cryopreservation of human pluripotent stem cells with standard slow-rate
protocols often is inefficient and can hardly be standardized. Vitrification that
means ultrafast freezing already showed very good viability and recovery rates
for this sensitive cell system, but is only applicable for low cell numbers,
bears a high risk of contamination, and can hardly be implemented under GxP
regulations. In this chapter, a sterile plate-based vitrification method for
adherent pluripotent stem cells and their derivatives is presented based on a
procedure and device for human embryonic stem cells developed by Beier et al.
(Cryobiology 66:8-16, 2013). This protocol overcomes the limitations of
conventional vitrification procedures resulting in the highly efficient
preservation of ready-to-use adherent pluripotent stem cells with the possibility
of vitrifying cells in multi-well formats for direct application in high
throughput screenings.
PMID- 28421502
TI - Chapter 18 Vitrification: A Reliable Method for Cryopreservation of Animal
Embryos.
AB - The impact of cryopreservation in assisted reproduction is increasingly
appreciated. Cells, oocytes, and embryos preserved under ultralow temperature can
endure storage for indefinite time with almost no alteration in their metabolic
and genetic components. Advances in cryopreservation and its applications to
preserve cells, gametes, and embryos offer opportunities in conservation of
biodiversity and dissemination of elite livestock germplasm. This chapter
describes the vitrification for cryopreservation of livestock embryos.
PMID- 28421503
TI - Chapter 19 Cryopreservation Effect on Genetic Function: Neonatal Outcomes.
AB - Cryopreservation is a well-established technique commonly used in clinical
practice. It is used widely for the conservation of gametes and embryos that will
be used later for insemination or in vitro fertilization. However, several
studies have shown that this technique can produce changes in messenger RNA
levels, in the epigenome and induce DNA damage. Although the embryo has potent
mechanisms for DNA repair, and molecular changes in spermatozoa are not
necessarily reflected in the embryo, it is important to explore new molecular
tests and diagnostic tools to design optimal cryopreservation protocols and avoid
undesirable molecular alterations. This chapter describes a protocol to quantify
the lesions produced by cryopreservation using a protocol previously published by
Rothfuss.
PMID- 28421504
TI - Chapter 20 Gavi-Automated Vitrification Instrument.
AB - Gavi is intended for use in a laboratory or clinic environment for the
preparation and vitrification of oocytes, cleavage stage embryos and blastocysts.
Gavi is designed to automate the equilibration steps in the vitrification process
to minimize the variability that occurs during cryopreservation. This automated
process reduces the potential for errors and ensures a standardized, repeatable
procedure for vitrification in a controlled, closed-system environment.
PMID- 28421505
TI - Appendix A: Cryotech(r) Vitrification Thawing.
AB - In the last 15-20 years, many centers are using vitrification as a method of
choice for cryopreservation of human oocytes and embryos. As vitrification
technologies have improved their success profiles, new applications seem to have
emerged, making IVF treatments more successful and more flexible.This appendix
describes the Cryotech(r) method, which is the latest "minimal volume approach"
method, suitable for cryopreservation of oocytes and embryos of any developmental
stage, including blastocysts. Dr. Masashige Kuwayama, who has introduced major
advances in oocyte and embryo cryopreservation, has developed this method. A
detailed protocol has been described with finer tips for the accurate use of the
method for perfect survival and safety.
PMID- 28421506
TI - Appendix B: Solid Surface Vitrification.
AB - Solid surface vitrification method involves direct contact of carrier loaded with
droplet containing gametes or embryos with precooled metal surface. Over the
years, following certain modifications, solid surface vitrification has emerged
as an efficient method for vitrifying human gametes and embryos. Here, we
describe the principle and methodology of solid surface vitrification.
PMID- 28421507
TI - Appendix C: Automated Vitrification of Mammalian Embryos on a Digital
Microfluidic Device.
AB - This chapter introduces a digital microfluidic device that automates sample
preparation for mammalian embryo vitrification. Individual microdroplets
manipulated on the microfluidic device were used as microvessels to transport a
single mouse embryo through a complete vitrification procedure. Advantages of
this approach, compared to manual operation and channel-based microfluidic
vitrification, include automated operation, cryoprotectant concentration gradient
generation, and feasibility of loading and retrieval of embryos.
PMID- 28421508
TI - Appendix D: Irvine Scientific(r) Vitrification System.
AB - This chapter will describe the use of the Irvine Scientific(r) vitrification and
warming solutions (Vit Kits(r)) along with a detailed protocol for the correct
use of the CryoTip(r) vitrification device for human embryos and oocytes.
Successful pregnancies have been reported after carrying out rapid vitrification
methods of oocytes, cleavage stage embryos, and blastocysts using the CryoTip(r)
(Popwell et al. Fertil Steril, 101:e20, 2014; Kuwayama et al. Reprod Biomed
11:608-614, 2005; Kuwayama et al. Fertil Steril 84:S187, 2005; Kuwayama et al.
Vitrification of human embryos using the CryoTip TM method. Reprod Biomed 11:608
614). Compared to other vitrification carrier devices, the CryoTip(r) is
considered a closed carrier for vitrification, thereby eliminating the
theoretical risk of disease transmission through contaminated liquid nitrogen
during cooling and storage (Bielanski et al. Cryobiology, 40:110-116, 2000). The
CryoTip(r) is cleared by the FDA and has CE mark approval as a closed device to
carry gametes or embryos in a specialized medium during cryopreservation
procedures and subsequent long-term storage in liquid nitrogen. The CryoTip(r)
has been shown to be a safe and reliable vitrification device, and when compared
to other open system vitrification devices, it has provided similar results
(Martino et al. Reprod Biol Endocrinol 11:27, 2013, Valbuena et al. Fertil Steril
97:209-217, 2012; Kuwayama et al. Reprod Biomed 11:608-614, 2005). The CryoTip(r)
has also been shown to be suitable for use as a vitrification device for the
cryopreservation of small volumes of sperm (Tanaka et al. Fertil Steril 90: S292,
2008).
PMID- 28421509
TI - Appendix E: Rapid-iTM: Closed Vitrification Device by Vitrolife.
AB - Cryopreservation of gametes and embryos is a growing technique in numerous
reproductive fields including human-assisted reproduction. With improved
understanding of embryo physiology and optimized culture conditions, there are
now more embryos than ever to vitrify for potential use in subsequent cycles.
Many gametes and embryos have been cryopreserved in open systems, but there are
concerns with regard to contamination from the liquid nitrogen and also cross
contamination between patients' germplasm. The development of the Rapid-iTM, a
closed vitrification device that does not use direct contact with liquid nitrogen
during vitrification or subsequent storage, will be discussed as well as clinical
protocols for human oocytes and embryos.
PMID- 28421510
TI - Appendix F: Quinn's Advantage Embryo Freeze Kit.
AB - Despite a large focus on the use of vitrification to cryopreserve embryos in
recent years, there are still arguments for the use of slow freezing for the
cleavage-stage embryo. Having said this, there are lessons to be learned from the
process of vitrification that could be applied to slow freezing to improve post
thaw survival and ultimately clinical pregnancy rates. Specifically, increasing
the concentration of sucrose in the freezing solution from 0.1 to 0.2 M and
subsequently increasing the sucrose concentrations in thawing solutions could
prove beneficial. The use of vitrification warming solutions in the thawing of
slow-frozen embryos may also be an option that not only improves survival but
also streamlines product purchasing and protocols within the laboratory.
PMID- 28421511
TI - Appendix G: Vitrification of Blastocysts Using VitriBlastTM and ThermoBlastTM:
Nidacon.
AB - This appendix describes the vitrification of blastocysts using VitriBlastTM (VBK)
and ThermoBlastTM (TBK) from Nidacon, Molndal, Sweden. The technique used and the
reason for not including DMSO in the medium at the production stage, but
including it separately in the kit, and the importance of collapsing the
blastocyst prior to vitrification will be explained and described.
PMID- 28421512
TI - New Insights into Cockroach Allergens.
AB - PURPOSE OF REVIEW: This review addresses the most recent developments on
cockroach allergen research in relation to allergic diseases, especially asthma.
RECENT FINDINGS: The number of allergens relevant to cockroach allergy has
recently expanded considerably up to 12 groups. New X-ray crystal structures of
allergens from groups 1, 2, and 5 revealed interesting features with implications
for allergen standardization, sensitization, diagnosis, and therapy. Cockroach
allergy is strongly associated with asthma particularly among children and young
adults living in inner-city environments, posing challenges for disease control.
Environmental interventions targeted at reducing cockroach allergen exposure have
provided conflicting results. Immunotherapy may be a way to modify the natural
history of cockroach allergy and decrease symptoms and asthma severity among
sensitized and exposed individuals. The new information on cockroach allergens is
important for the assessment of allergen markers of exposure and disease, and for
the design of immunotherapy trials.
PMID- 28421513
TI - Primary Prevention of Food Allergy.
AB - Food allergy is estimated to affect approximately 8% of children in the USA. This
is a disease without any known treatment or cure and, for some, a disease that
can be quite severe, even life-threatening. While recent advances in potential
treatment have made remarkable strides, with two food-targeted immunotherapy
products now in phase III trials, perhaps the biggest gains in the field have
come in the advent of potential preventative strategies to avoid the development
of food allergy in high-risk individuals. There have been multiple, randomized,
controlled trials (RCTs) performed in the past 5 years that have demonstrated
significant risk reduction from early allergen introduction. These include two
trials for early peanut introduction and five trials for early egg introduction
in the first year of life. The results indicate that primary prevention of food
allergy through early allergen introduction may represent a strategy that could
potentially avert tens of thousands of children from becoming food allergic. In
support of the data for peanut, the National Institute of Allergy and Infectious
Diseases recently sponsored an addendum to the 2010 food allergy guidelines,
specifically recommending peanut be introduced in both high- and standard-risk
infants to reduce the risk of developing peanut allergy. To date, no formal
recommendations have been made for egg, however. This review will focus on the
latest evidence supporting early introduction as a strategy to prevent food
allergy, as well as on practical aspects for its successful implementation.
PMID- 28421514
TI - CORR Insights(r): Vancomycin Prophylaxis for Total Joint Arthroplasty:
Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than
Cefazolin.
PMID- 28421515
TI - CORR Insights(r): Can a Bayesian Belief Network Be Used to Estimate 1-year
Survival in Patients With Bone Sarcomas?
PMID- 28421516
TI - CORR Insights(r): What is the Responsiveness and Respondent Burden of the New
Knee Society Score?
PMID- 28421517
TI - CORR Insights(r): What Is the Timing of General Health Adverse Events That Occur
After Total Joint Arthroplasty?
PMID- 28421518
TI - Empirical research on coordination evaluation and sustainable development
mechanism of regional logistics and new-type urbanization: a panel data analysis
from 2000 to 2015 for Liaoning Province in China.
AB - As the largest developing country in the world, China has witnessed fast-paced
urbanization over the past three decades with rapid economic growth. In fact,
urbanization has been not only shown to promote economic growth and improve the
livelihood of people but also can increase demands of regional logistics.
Therefore, a better understanding of the relationship between urbanization and
regional logistics is important for China's future sustainable development. The
development of urban residential area and heterogeneous, modern society as well
regional logistics are running two abreast. The regional logistics can promote
the development of new-type urbanization jointly by promoting industrial
concentration and logistics demand, enhancing the residents' quality of life and
improving the infrastructure and logistics technology. In this paper, the index
system and evaluation model for evaluating the development of regional logistics
and the new-type urbanization are constructed. Further, the econometric analysis
is utilized such as correlation analysis, co-integration test, and error
correction model to explore relationships of the new-type urbanization
development and regional logistics development in Liaoning Province. The results
showed that there was a long-term stable equilibrium relationship between the new
type urbanization and regional logistics. The findings have important
implications for Chinese policymakers that on the path towards a sustainable
urbanization and regional reverse, this must be taken into consideration. The
paper concludes providing some strategies that might be helpful to the
policymakers in formulating development policies for sustainable urbanization.
PMID- 28421519
TI - Calcite precipitates in Slovenian bottled waters.
AB - Storage of bottled waters in varying ambient conditions affects its
characteristics. Different storage conditions cause changes in the initial
chemical composition of bottled water which lead to the occurrence of
precipitates with various morphologies. In order to assess the relationship
between water composition, storage conditions and precipitate morphology, a study
of four brands of Slovenian bottled water stored in PET bottles was carried out.
Chemical analyses of the main ions and measurements of the physical properties of
water samples were performed before and after storage of water samples at
different ambient conditions. SEM/EDS analysis of precipitates was performed
after elapsed storage time. The results show that the presence of Mg2+, SO42-,
SiO2, Al, Mn and other impurities such as K+, Na+, Ba and Sr in the water
controlled precipitate morphology by inhibiting crystal growth and leading to
elongated rhombohedral calcite crystal forms which exhibit furrowed surfaces and
calcite rosettes. Different storage conditions, however, affected the number of
crystallization nuclei and size of calcite crystals. Hollow calcite spheres
composed of cleavage rhombohedrons formed in the water with variable storage
conditions by a combination of evaporation and precipitation of water droplets
during high temperatures or by the bubble templating method.
PMID- 28421520
TI - Evaluation of passive sampling of gaseous mercury using different sorbing
materials.
AB - Atmospheric mercury monitoring is essential because of its potential human health
and ecological impacts. Current automated monitoring systems include limitations
such as high cost, complicated configuration, and electricity requirements.
Passive samplers require no electric power and are more appropriate for screening
applications and long-term monitoring. Sampling rate is a major factor to
evaluate the performance of a passive sampler. In this study, laboratory
experiments were carried out using an exposure chamber to search for high
efficiency sorbents for gaseous mercury. Four types of sorbents, including sulfur
impregnated carbon (SIC), chlorine-impregnated carbon (CIC), bromine-impregnated
carbon (BIC), and gold-coated sand (GCS) were evaluated under a wide range of
meteorological parameters, including temperature, relative humidity, and wind
speed. The results showed that the four sorbents all have a high sampling rate
above 0.01 m3g-1 day-1, and wind speed has a positive correlation with the
sampling rate. Under different temperature and relative humidity, the sampling
rate of SIC keeps stable. The sampling rate of CIC and BIC shows a negative
correlation with temperature, and GCS is influenced by all the three
meteorological factors. Furthermore, long-term experiments were carried out to
investigate the uptake capacity of GCS and SIC. Uptake curves show that the mass
amount of sorbent in a passive sampler can influence uptake capacity. In the
passive sampler, 0.9 g SIC or 0.9 g GCS can achieve stable uptake efficiency for
at least 110 days with gaseous mercury concentration at or below 2 ng/m3. For
mercury concentration at or below 21 ng/m3, 0.9 g SIC can maintain stable uptake
efficiency for 70 days, and 0.9 g GCS can maintain stability for 45 days.
PMID- 28421521
TI - Selective adsorption of Pb (II) over the zinc-based MOFs in aqueous solution
kinetics, isotherms, and the ion exchange mechanism.
AB - Two series of metal-organic frameworks (MOFs) with similar formula units but
different central metal ions (M) or organic linkers (L), M-BDC (BDC =
terephthalate, M = Zn, Zr, Cr, or Fe), or Zn-L (L = imidazolate-2-methyl, BDC,
BDC-NH2), were prepared and employed as the receptors for adsorption lead ions.
It was found that the Zn-BDC exhibited a much higher adsorption capacity than the
other M-BDC series with various metal ions which have very closely low capacities
at same conditions. Furthermore, the Zn-L (L = imidazolate-2-methyl, BDC, BDC
NH2) still have highly efficient adsorption capacity of lead ions, although the
adsorption capacity varies with different ligand, as well as the adsorption rate
and the equilibrium pH of the solution. This significant high adsorption over Zn
L, different from other M-BDC series with various metal ions (Zr, Cr, or Fe), can
be explained by ion exchange between the central metal ions of Zn-L and lead ion
in solution. Based on the analysis of FT-IR, X-ray diffraction pattern, the
nitrogen adsorption isotherms, the zeta potentials, and the results, a plausible
adsorption mechanism is proposed. When equivalent Zn-L were added to equal volume
of aqueous solution with different concentration of lead ion, the content of zinc
ion in the solution increases with the increase of the initial concentration of
lead ions. The new findings could provide a potential way to fabricate new metal
organic frameworks with high and selective capacities of the heavy metal ions.
PMID- 28421522
TI - Individual and combined inhibition of phenol and thiocyanate on microbial
activity of partial nitritation.
AB - This study evaluated the individual and interactive effect of phenol and
thiocyanate (SCN-) on partial nitritation (PN) activity using batch test and
response surface methodology. The IC50 of phenol and SCN- on PN sludge were 5.6
and 351 mg L-1, respectively. The PN sludge was insensitive to phenol and SCN- at
levels lower than 1.77 and 43.3 mg L-1, respectively. A regression model equation
was developed and validated to predict the relative specific respiration rate
(RSRR) of PN sludge exposed to different phenol and SCN- concentrations. In the
range of independent variables, the most severe inhibition was observed with a
valley value (17%) for RSRR, when the phenol and SCN- concentrations were 4.08
and 198 mg L-1, respectively. An isobole plot was used to judge the combined
toxicity of phenol and SCN-, and the joint inhibitory effect was variable
depending on the composition and concentration of the toxic components.
Furthermore, the toxic compounds showed independent effects, which is the most
common type of combined toxicity.
PMID- 28421523
TI - Response of marine benthic fauna to thin-layer capping with activated carbon in a
large-scale field experiment in the Grenland fjords, Norway.
AB - A field experiment with thin-layer capping was conducted in the Grenland fjords,
Norway, for remediation in situ of mercury and dioxin-contaminated sediments.
Experimental fields at 30 and 95 m depth were capped with (i) powdered activated
carbon (AC) mixed with clay (AC+cla'y), (ii) clay, and (iii) crushed limestone.
Ecological effects on the benthic community and species-feeding guilds were
studied 1 and 14 months after capping, and a total of 158 species were included
in the analyses. The results show that clay and limestone had only minor effects
on the benthic community, while AC+clay caused severe perturbations. AC+clay
reduced the abundance, biomass, and number of species by up to 90% at both 30 and
95 m depth, and few indications of recovery were found during the period of this
investigation. The negative effects of AC+clay were observed on a wide range of
species with different feeding strategies, although the suspension feeding
brittle star Amphiura filiformis was particularly affected. Even though activated
carbon is effective in reducing sediment-to-water fluxes of dioxins and other
organic pollutants, this study shows that capping with powdered AC can lead to
substantial disturbances to the benthic community.
PMID- 28421524
TI - Distance-dependent varieties of microbial community structure and metabolic
functions in the rhizosphere of Sedum alfredii Hance during phytoextraction of a
cadmium-contaminated soil.
AB - The recovery of microbial community and activities is crucial to the remediation
of contaminated soils. Distance-dependent variations of microbial community
composition and metabolic characteristics in the rhizospheric soil of
hyperaccumulator during phytoextraction are poorly understood. A 12-month
phytoextraction experiment with Sedum alfredii in a Cd-contaminated soil was
conducted. A pre-stratified rhizobox was used for separating sub-layer
rhizospheric (0-2, 2-4, 4-6, 6-8, 8-10 mm from the root mat)/bulk soils. Soil
microbial structure and function were analyzed by phospholipid fatty acid (PLFA)
and MicroRespTM methods. The concentrations of total and specified PLFA
biomarkers and the utilization rates for the 14 substrates (organic carbon) in
the 0-2-mm sub-layer rhizospheric soil were significantly increased, as well as
decreased with the increase in the distance from the root mat. Microbial
structure measured by the ratios of different groups of PLFAs such as
fungal/bacterial, monounsaturated/saturated, ratios of Gram-positive to Gram
negative (GP/GN) bacterial, and cyclopropyl/monoenoic precursors and 19:0
cyclo/18:1omega7c were significantly changed in the 0-2-mm soil. The PLFA
contents and substrate utilization rates were negatively correlated with pH and
total, acid-soluble, and reducible fractions of Cd, while positively correlated
with labile carbon. The dynamics of microbial community were likely due to root
exudates and Cd uptake by S. alfredii. This study revealed the stimulations and
gradient changes of rhizosphere microbial community through phytoextraction, as
reduced Cd concentration, pH, and increased labile carbons are due to the
microbial community responses.
PMID- 28421525
TI - The electrochemical selective reduction of NO using CoSe2@CNTs hybrid.
AB - Converting the NO from gaseous pollutant into NH4+ through electrocatalytical
reduction using cost-effective materials holds great promise for pollutant
purifying and resources recycling. In this work, we developed a highly selective
and stable catalyst CoSe2 nanoparticle hybridized with carbon nanotubes
(CoSe2@CNTs). The CoSe2@CNTs hybrid catalysts performed an extraordinary high
selectivity for NH4+ formation in NO electroreduction with minimal N2O production
and H2 evolution. The specific spatial structure of CoSe2 is conductive to the
predominant formation of N-H bond between the N from adsorbed NO and H and
inhibition of N-N formation from adjacent adsorbed NO. It was also the first time
to convert the coordinated NO into NH4+ using non-noble metal catalysis.
Moreover, the original concept of employing CoSe2 as eletrocatalyst for NO
hydrogenation presented in this work can broaden horizons and provide new
dimensions in the design of new highly efficient catalysts for NH4+ synthesis in
aqueous solution.
PMID- 28421526
TI - Impact of the toxicity of Cylindrospermopsis raciborskii (Woloszynska) Seenayya &
Subba Raju on laboratory rats in vivo.
AB - In vivo laboratory studies of toxicity were performed on Wistar rats using a
methanol extract produced by the natural population of Cylindrospermopsis
raciborskii (abundance of 2.13 * 105 trichomes mL-1) collected at Aleksandrovac
Lake (Serbia). HPLC analysis showed that the extract contains 6.65 MUg
cylindrospermopsin (CYN) mg-1. The rats were killed 24 or 72 h after a single
intraperitoneal injection of C. raciborskii extract in concentrations of 1500,
3000, 6000 and 12,000 MUg kg-1 body weight (bw) and an equivalent amount of CYN
as present in the highest dose of the extract (79.80 MUg CYN kg-1 bw). The
genotoxic effect on the livers treated with C. raciborskii was evaluated using
comet assay and potential induction of oxidative stress as the toxicity mechanism
associated with the presence of CYN in extract. The results from the analyses of
DNA damage in the comet tail length, tail moment and percentage of DNA in the
tail in the liver indicated that administration of extract and CYN present
statistically significant difference when compared with the negative control
group. Although an increase in the frequency of selected parameters induced by
the CYN was observed in the liver, this damage was less than the damage resulting
from the administration of the highest dose of extract. The changes in the
biochemical parameters of the hepatic damage showed that the application of
single doses of the extract and CYN did not cause serious liver damage in rats.
The extract and CYN significantly increased oxidative stress in rats' liver after
a single exposure.
PMID- 28421527
TI - Spatio-temporal assessment and trend analysis of surface water salinity in the
coastal region of Bangladesh.
AB - The study was designed to collect water samples over two seasons-wet-monsoon
season (n = 96) (March-April) and dry-monsoon season (n = 44) (September-October)
to understand the seasonal variation in anion and cation hydrochemistry of the
coastal rivers and estuaries contributing in the spatial trend in salinity.
Hydrochemical examination of wet-monsoon season primarily revealed Ca-Mg-HCO3
type (66%) and followed by Na-Cl type (17.70%) water. In the dry-monsoon season,
the scenario reversed with primary water being Na-Cl type (52.27%) followed by Ca
Mg-HCO3 type (31.81%). Analysis of Cl/Br molar ratio vs. Cl (mg/L) depicted
sampling area affected by seawater intrusion (SWI). Spatial analysis by ordinary
kriging method confirmed approximately 77% sample in the dry-monsoon, and 34% of
the wet-monsoon season had shown SWI. The most saline-intruded areas in the wet
monsoon seasons were extreme south-west coastal zone of Bangladesh, lower Meghna
River floodplain and Meghna estuarine floodplain and south-eastern part of
Chittagong coastal plains containing the districts of Chittagong and Cox's Bazar
adjacent to Bay of Bengal. In addition, mid-south zone is also affected slightly
in the dry-monsoon season. From the analyses of data, this study could further
help to comprehend seasonal trends in the hydrochemistry and water quality of the
coastal and estuarine rivers. In addition, it can help policy makers to obligate
some important implications for the future initiatives taken for the management
of land, water, fishery, agriculture and environment of coastal rivers and
estuaries of Bangladesh.
PMID- 28421528
TI - Postnatal LPS Challenge Impacts Escape Learning and Expression of Plasticity
Factors Mmp9 and Timp1 in Rats: Effects of Repeated Training.
AB - Bacterial intoxication associated with inflammatory conditions during development
can impair brain functions, in particular evolutionarily novel forms of memory,
such as explicit learning. Little is known about the dangers of early-life
inflammation on more basic forms of learning, for example, the acquisition of
motor escape abilities, which are generally better preserved under pathological
conditions. To address this limitation in knowledge, an inflammatory response was
elicited in Wistar pups by lipopolysaccharide (LPS) injections (25 MUg/kg) on
postnatal days P15, P18 and P21. The acquisition of escape behaviour was tested
from P77 by active avoidance footshock model and water maze. Open-field behaviour
and blood corticosterone levels were also measured. Rat brain tissue was
collected from pups 2 h post-injection and from adult rats which either underwent
escape training on P77-P81 or remained untrained. mRNA levels of developmental
brain plasticity factors MMP-9 and TIMP-1 were investigated in the medial
prefrontal cortex and ventral/dorsal hippocampus. LPS-challenged rats displayed
moderately deficient escape responses in both memory tests, increased freezing
behaviour and, surprisingly, reduced blood cortisol levels. Mmp9 and Timp1, and
their ratio to one another, were differentially altered in pups versus adult
untrained rats but remained unchanged overall in rats trained in either learning
task. Together, our data indicate that systemic pro-inflammatory response during
early postnatal development has long-lasting effects, including on the
acquisition of motor escape abilities and plasticity factor expression, into
adulthood. Our data suggest that altered stress response could possibly mediate
these deviations and repeated training might generate positive effects on
plasticity under the employed conditions.
PMID- 28421529
TI - Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is
Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia.
AB - Ketamine may prove to be a potential candidate in treating the widespread drug
addiction/substance abuse epidemic among patients with schizophrenia. Clinical
studies have shown ketamine to reduce cocaine and heroin cravings. However, the
use of ketamine remains controversial as it may exacerbate the symptoms of
schizophrenia. Therefore, the aim of this study is to characterize the effects of
ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM)
acetate rat model on operant IV methamphetamine (METH) self-administration. MAM
was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor
activity test and later IV self-administration (IVSA) were then performed in the
male offspring followed by a period of forced abstinence and relapse of METH
taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg)
was administered intraperitoneally 30 min prior to the self-administration
session. As documented previously, the MAM rats showed a lack of habituation in
the locomotor activity test but developed stable maintenance of METH self
administration with no difference in operant behaviour to control animals.
Results show that ketamine treatment significantly reduced the METH intake in the
control animals but not in MAM animals. Ketamine effect on METH self
administration may be explained by increased glutamatergic signalling in the
prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition
of GABA interneurons which was shown to be impaired in the MAM rats. This
mechanism may at least partly explain the clinically proven anti-craving
potential of ketamine and allow development of more specific anti-craving
medications with fewer risks.
PMID- 28421530
TI - Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of
Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.
AB - Occurrence of stroke cases displays a time-of-day variation in human. However,
the mechanism linking circadian rhythm to the internal response mechanisms
against pathophysiological events after ischemic stroke remained largely unknown.
To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R)
injury were investigated in mice in which the ischemic stroke induced at four
different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18).
Besides infarct volume and brain swelling, neuronal survival, apoptosis,
ischemia, and circadian rhythm related proteins were examined using
immunohistochemistry, Western blot, planar surface immune assay, and liquid
chromatography-mass spectrometry tools. Here, we present evidence that midnight
(ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct
volume, brain swelling, neurological deficit score, neuronal survival, and
decreased apoptotic cell death compared with ischemia induced at other time
points, which were associated with increased expressions of circadian proteins
Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover,
ribosomal protein S6, mTOR, and Bad were also significantly increased, while the
levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were
decreased at this time point compared to ZT0 (06:00). Furthermore, detailed
proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA
levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared
with early morning. Our results indicate that nighttime I/R injury results in
less severe neuronal damage, with increased neuronal survival, increased levels
of survival kinases and circadian clock proteins, and also alters the circadian
related proteins.
PMID- 28421531
TI - Retraction Note to "SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and
Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma".
PMID- 28421532
TI - Matrix Metalloproteinase-8 Inhibition Prevents Disruption of Blood-Spinal Cord
Barrier and Attenuates Inflammation in Rat Model of Spinal Cord Injury.
AB - After spinal cord injury (SCI), tight junction (TJ) protein degradation increases
permeability and disrupts the blood-spinal cord barrier (BSCB). The BSCB is
primarily formed of endothelial cell, which forms a specialized tight seal due to
the presence of TJs. BSCB disruption after SCI allows neutrophil infiltration.
Matrix metalloproteinase (MMP)-8 is believed to be mainly expressed by
neutrophils and is quickly released upon neutrophil activation. Here, we
determined whether MMP-8 is involved in the TJ protein degradation in endothelial
cells and also determined its role in the neuroinflammation after SCI. MMP-8
recombinant protein treatment increases the TNF-alpha expression and decreased
the TJ (occludin and zonula occludens-1) protein expression in the endothelial
cells. Likewise, specific MMP-8 inhibitor (MMP-8I) significantly prevented the
TNF-alpha-induced decrease in the expression of TJ protein in endothelial cells.
Furthermore, MMP-8 expression was significantly increased 1 and 3 days after
moderate compression (35 g for 5 min at T10 level) SCI, whereas TJ protein levels
decreased as determined qRT-PCR, western blotting, and immunohistochemistry. MMP
8 was inhibited directly using a MMP-8I (5 mg/kg) and indirectly by reducing
neutrophil infiltration with sivelestat sodium (50 mg/kg) or using the
antioxidant N-acetyl-L-cysteine (100 mg/kg). The MMP-8I significantly decreased
TNF-alpha expression, IL-6, and iNOS expression and increased TJ protein
expression after SCI. In addition, MMP-8I significantly lessens the amount of
Evans blue dye extravasation observed after injury. Thus, our result suggests
that MMP-8 plays an imperative role in inflammation and degradation of TJ
proteins. Increased MMP-8 expression was associated with the early inflammatory
phase of SCI. Inhibiting MMP-8 significantly attenuated SCI-induced inflammation,
BSCB breakdown, and cell injury.
PMID- 28421533
TI - Changes in the Prefrontal Glutamatergic and Parvalbumin Systems of Mice Exposed
to Unpredictable Chronic Stress.
AB - The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known
risk factor of mood disorders including anxiety and depression. Abnormalities in
PFC functioning have been well described in humans displaying stress-induced
depressive symptoms, and hypoactivity of the PFC is now recognized to be a key
feature of the depressed brain. However, little is known about the causes and
mechanisms leading to this altered prefrontal functional activity in the context
of stress-related mood disorders. We previously showed that unpredictable chronic
mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV),
an activity-dependent calcium-binding albumin protein expressed in a specific
subtype of GABAergic neurons, highlighting a potential mechanism through which
chronic stress leads to hypofunction of the PFC. In this study, we aimed to
investigate the mechanisms by which chronic stress alters the prefrontal GABA
system. We hypothesized that chronic stress-induced enhancement of glutamatergic
transmission in the PFC is a crucial contributing factor to changes within the
prefrontal GABAergic and, specifically, PV system. BALB/c male and female mice
were exposed to daily handling (control) or 2 or 4 weeks of UCMS. Female mice
displayed a more severe altered phenotype than males, as shown by increased
anxiety- and depressive-like behaviors and deficits in PFC-dependent cognitive
abilities, particularly after exposure to 2 weeks of UCMS. This behavioral
phenotype was paralleled by a large increase in prefrontal PV messenger RNA
(mRNA) and number of PV-expressing neurons, supporting our previous findings. We
further showed that the expression of pre- and postsynaptic markers of
glutamatergic transmission (VGlut1 presynaptic terminals and pERK1/2,
respectively) onto PV neurons was increased by 2 weeks of UCMS in a sex-specific
manner; this was associated with sex-specific changes in the mRNA expression of
the NR2B subunit of the NMDA receptor. These findings provide evidence of
increased glutamatergic transmission onto prefrontal PV neurons, particularly in
female mice, which could potentially contribute to their increased PV expression
and the extent of their behavioral impairment following UCMS. Finally, our
analysis of activity of subcortical regions sending glutamatergic afferents to
the PFC reveals that glutamatergic neurons from the basolateral amygdala might be
specifically involved in UCMS-induced changes in prefrontal glutamatergic
transmission.
PMID- 28421534
TI - Immune Alterations in CD8+ T Cells Are Associated with Neuronal C-C and C-X-C
Chemokine Receptor Regulation Through Adenosine A2A Receptor Signaling in a BTBR
T+ Itpr3tf/J Autistic Mouse Model.
AB - Associative studies on a range of neurodevelopmental disorders have identified
relationships between behavioral deficits and immune system function. The BTBR T+
Itpr3tf/J (BTBR) mouse strain displays aberrant characteristics in its social
behavior and immune responses, providing a significant opportunity to examine the
relationship between behavior and the immune system. This study investigated the
influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors
involved in autism in the BTBR mouse model. A2A receptors have previously been
targeted in clinical trials by potential therapeutics with neuroprotective,
immunomodulatory, and analgesic properties. In this study, we examined the
effects of A2A receptor antagonist SCH5826 (SCH) and A2A receptor agonist
CGS21680 (CGS) on C-C and C-X-C chemokine receptors (CCR3, CCR4, CCR5, CCR6,
CCR7, CXCR3, CXCR4, and CXCR5) on splenic CD8+ T cells in the BTBR autistic mouse
model. We also assessed the C-C and C-X-C chemokine receptors mRNA levels in
brain tissue. Our results showed that CCR3+, CCR4+, CCR5+, CCR6+, CCR7+, CXCR3+,
CXCR4+, and CXCR5+ production in splenic CD8+ T cells decreased significantly in
BTBR-CGS-treated mice in comparison with that in BTBR control and BTBR-SCH
treated mice. In addition, RT-PCR analysis revealed decreased gene expression
levels for C-C and C-X-C chemokine receptors in the brain tissue of BTBR-CGS
treated mice, whereas these levels were significantly increased in BTBR control
and BTBR-SCH-treated mice. Our results suggest that treating BTBR mice with CGS
decreases C-C and C-X-C chemokine receptor signaling and might therefore provide
a unique avenue for developing future therapies for autism and neuroimmunological
disorders.
PMID- 28421535
TI - MicroRNA Metabolism and Dysregulation in Amyotrophic Lateral Sclerosis.
AB - MicroRNAs (miRNAs) are a subset of endogenous, small, non-coding RNA molecules
involved in the post-transcriptional regulation of eukaryotic gene expression.
Dysregulation in miRNA-related pathways in the central nervous system (CNS) is
associated with severe neuronal injury and cell death, which can lead to the
development of neurodegenerative disorders, such as amyotrophic lateral sclerosis
(ALS). ALS is a fatal adult onset disease characterized by the selective loss of
upper and lower motor neurons. While the pathogenesis of ALS is still largely
unknown, familial ALS forms linked to TAR DNA-binding protein 43 (TDP-43) and
fused in sarcoma (FUS) gene mutations, as well as sporadic forms, display changes
in several steps of RNA metabolism, including miRNA processing. Here, we review
the current knowledge about miRNA metabolism and biological functions and their
crucial role in ALS pathogenesis with an in-depth analysis on different pathways.
A more precise understanding of miRNA involvement in ALS could be useful not only
to elucidate their role in the disease etiopathogenesis but also to investigate
their potential as disease biomarkers and novel therapeutic targets.
PMID- 28421537
TI - Satb2 Ablation Impairs Hippocampus-Based Long-Term Spatial Memory and Short-Term
Working Memory and Immediate Early Genes (IEGs)-Mediated Hippocampal Synaptic
Plasticity.
AB - Special AT-rich sequence-binding protein 2 (Satb2) is a protein binding to the
matrix attachment regions of DNA and important for gene regulation. Patients with
SATB2 mutation usually suffer moderate to severe mental retardation. However, the
mechanisms for the defects of intellectual activities in patients with SATB2
mutation are largely unclear. Here we established the heterozygous Satb2 mutant
mice and Satb2 conditional knockout mice to mimic the patients with SATB2
mutation and figured out the role of Satb2 in mental activities. We found that
the spatial memory and working memory were significantly damaged in the
heterozygous Satb2 mutant mice, early postnatal Satb2-deficient mice (CaMKIIalpha
Cre+Satb2fl/fl mice), and adult Satb2 ablation mice (Satb2fl/fl mice injected
with CaMKIIalpha-Cre virus). Functionally, late phase long-term potentiation (L
LTP) in these Satb2 mutant mice was greatly impaired. Morphologically, in CA1
neurons of CaMKIIalpha-Cre+Satb2fl/fl mice, we found decreased spine density of
the basal dendrites and less branches of apical dendrites that extended into
lacunar molecular layer. Mechanistically, expression levels of immediate early
genes (IEGs) including Fos, FosB, and Egr1 were significantly decreased after
Satb2 deletion. And, Satb2 could regulate expression of FosB by binding to the
promoter of FosB directly. In general, our study uncovers that Satb2 plays an
important role in spatial memory and working memory by regulating IEGs-mediated
hippocampal synaptic plasticity.
PMID- 28421536
TI - Lysosomal Quality Control in Prion Diseases.
AB - Prion diseases are transmissible, familial or sporadic. The prion protein (PrP),
a normal cell surface glycoprotein, is ubiquitously expressed throughout the
body. While loss of function of PrP does not elicit apparent phenotypes,
generation of misfolded forms of the protein or its aberrant metabolic isoforms
has been implicated in a number of neurodegenerative disorders such as scrapie,
kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler
Scheinker and bovine spongiform encephalopathy. These diseases are all
phenotypically characterised by spongiform vacuolation of the adult brain, hence
collectively termed as late-onset spongiform neurodegeneration. Misfolded form of
PrP (PrPSc) and one of its abnormal metabolic isoforms (the transmembrane CtmPrP)
are known to be disease-causing agents that lead to progressive loss of structure
or function of neurons culminating in neuronal death. The aberrant forms of PrP
utilise and manipulate the various intracellular quality control mechanisms
during pathogenesis of these diseases. Amongst these, the lysosomal quality
control machinery emerges as one of the primary targets exploited by the disease
causing isoforms of PrP. The autophagosomal-lysosomal degradation pathway is
adversely affected in multiple ways in prion diseases and may hence be regarded
as an important modulator of neurodegeneration. Some of the ESCRT pathway
proteins have also been shown to be involved in the manifestation of disease
phenotype. This review discusses the significance of the lysosomal quality
control pathway in affecting transmissible and familial types of prion diseases.
PMID- 28421538
TI - Roles of Nitric Oxide Synthase Isoforms in Neurogenesis.
AB - Nitric oxide (NO), a free radical gas, acts as a neurotransmitter or
neuromodulator in the central nervous system (CNS). It has been widely explored
as a mediator of neuroinflammation, neuronal damages, and neurodegeneration at
its pathological levels. Recently, increasing evidence suggests that NO plays key
roles in mediating adult neurogenesis, the process of neural stem cells (NSCs) to
generate newborn neurons for replacing damaged neurons or maintaining the
function of the brain. NO synthase (NOS) is a major enzyme catalyzing the
generation of NO in the brain. Recent studies indicate that three homologous NOS
isoforms are involved in the proliferation of NSCs and neurogenesis. Therefore,
the impact of NOS isoforms on NSC functions needs to be elucidated. Here, we
summarize the studies on the role of NO and NOS with different isoforms in NSC
proliferation and neurogenesis with the focus on introducing action mechanisms
involved in the regulation of NSC function. This growing research area provides
the new insight into controlling NSC function via regulating NO microenvironment
in the brain. It also provides the evidence on targeting NOS for the treatment of
brain diseases.
PMID- 28421539
TI - alpha-Synuclein Aggregates with beta-Amyloid or Tau in Human Red Blood Cells:
Correlation with Antioxidant Capability and Physical Exercise in Human Healthy
Subjects.
AB - Neurodegenerative disorders (NDs) are characterized by abnormal
accumulation/misfolding of specific proteins, primarily alpha-synuclein (alpha
syn), beta-amyloid1-42 (Abeta), and tau, in both brain and peripheral tissue. In
addition to homo-oligomers, the role of alpha-syn interactions with Abeta or tau
has gradually emerged. The altered protein accumulation has been related to both
oxidative stress and physical activity; nevertheless, no correlation among the
presence of peripheral alpha-syn hetero-aggregates, antioxidant capacity, and
physical exercise has been discovered as of yet. Herein, the content of alpha
syn, Abeta, tau, and of their heterocomplexes was determined in red blood cells
(RBCs) of healthy subjects (sedentary and athletes). Such parameters were related
to the extent of the antioxidant capability (AOC), a key marker of oxidative
stress in aging-related pathologies, and to physical exercise, which is known to
play an important preventive role in NDs and to modulate oxidative stress. Tau
content and plasma AOC toward hydroxyl radicals were both reduced in older or
sedentary subjects; in contrast, alpha-syn and Abeta accumulated in elderly
subjects and showed an inverse correlation with both hydroxyl AOC and the level
of physical activity. For the first time, alpha-syn heterocomplexes with Abeta or
tau were quantified and demonstrated to be inversely related to hydroxyl AOC.
Furthermore, alpha-syn/Abeta aggregates were significantly reduced in athletes
and inversely correlated with physical activity level, independent of age. The
positive correlation between antioxidant capability/physical activity and reduced
protein accumulation was confirmed by these data and suggested that peripheral
alpha-syn heterocomplexes may represent new indicators of ND-related protein
misfolding.
PMID- 28421540
TI - Maternal Folic Acid Supplementation During Pregnancy Improves Neurobehavioral
Development in Rat Offspring.
AB - Maternal folate status during pregnancy may influence central nervous system
(CNS) development in offspring. However, the recommended intakes of folic acid
for women of childbearing age differ among countries and there is still no
consensus about whether folic acid should be supplemented continuously throughout
pregnancy. We hypothesized that folic acid supplementation may be more beneficial
for offspring's neurobehavioral development if prolonged throughout pregnancy
instead of being limited to the periconceptional period. In this study, three
groups of the female rats were fed folate-normal, folate-deficient, or folate
supplemented diets throughout pregnancy. In another group, the female rats were
fed folate-supplemented diet from mating for 10 consecutive days and then fed
folate-normal diet for remainder days of pregnancy. The results showed that
maternal folate deficiency increased plasma homocysteine (Hcy) concentration in
dams, delayed early sensory-motor reflex development, impaired spatial learning
and memory ability, and caused ultrastructural damages in the hippocampus of
offspring. Maternal folic acid supplementation would be more effective on
improving early sensory-motor reflex development and spatial learning and memory
ability in offspring if prolonged throughout pregnancy instead of being limited
to the periconceptional period. In conclusion, prolonged maternal folic acid
supplementation throughout pregnancy would be more effective in neurobehavioral
development of offspring in rats.
PMID- 28421541
TI - Systemic Inflammation as a Driver of Brain Injury: the Astrocyte as an Emerging
Player.
AB - Severe systemic inflammation has strong effects on brain functions, promoting
permanent neurocognitive dysfunction and high mortality rates. Additionally,
hippocampal damage seems to be directly involved in this process and astrocytes
play an important role in neuroinflammation and in the neuroimmune response.
However, the contribution of the astrocytes to the pathology of acute brain
dysfunction is not well understood. Recently, our group established a protocol
for obtaining astrocyte cultures from mature brain to allow the characterization
of these cells and their functions under pathologic conditions. The present study
was designed to characterize astrocyte function after acute systemic inflammation
induced by cecal ligation and perforation (CLP). Hippocampal astrocyte cultures
from CLP animals presented increased levels of tumor necrosis factor-alpha (TNF
alpha), interleukin (IL)-1beta, IL-6, IL-18, and cyclooxygenase-2 and decreased
levels of IL-10. This proinflammatory profile was accompanied by an increase in
Toll-like receptor (TLR)2 mRNA expression levels and no change either in TLR4 or
in vascular endothelial growth factor (VEGF) gene expression. These alterations
were associated with increased expressions of p21, nuclear factor kappa B
(NFkappaB), and inducible nitric oxide synthase (iNOS) in astrocytes from CLP
animals. The same parameters were also evaluated in whole hippocampal tissue, but
differences in this profile were found compared to hippocampal astrocyte cultures
from CLP, reflecting an interaction between other central nervous system cell
types, which may mask specific astrocytic changes. These results improve our
understanding of the mechanisms by which astrocytes react against systemic
inflammation, and suggest these cells to be potential targets for therapeutic
modulation.
PMID- 28421543
TI - Changing and partially successful local institutions for harvest of thatch palm
leaves.
AB - In some cases, users of common-pool resources (CPR) successfully govern and
manage these for collective benefit but in other cases they fail to do so. When
evaluating the success of local institutions for CPR management, however,
researchers have not always clearly distinguished between success in terms of
compliance and endurance, and success in terms of the socio-economic and
environmental outcomes of the management. This study focused on the governance
and management of wayuri palms (Pholidostachys synanthera robusta), whose leaves
are harvested for roof thatch, in Ecuadorian Amazonia. Combining ethnographic
methods with field botanic inventory, it was shown that although local
institutions regulating leaf harvest had existed for longer than living memory,
and the degree of compliance was high, they did not prevent exhaustion of the
resource base, only delayed it.
PMID- 28421542
TI - Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic
Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.
AB - Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral
deficits. Previous evidences have suggested that neural stem cell (NSC)
transplantation could facilitate functional recovery from brain insults, but
their underlying mechanisms remains to be elucidated. Here, we established TBI
model by an electromagnetic-controlled cortical impact device in the rats. Then,
5 MUl NSCs (5.0 * 105/MUl), derived from green fluorescent protein (GFP)
transgenic mouse, was transplanted into the traumatic brain regions of rats at 24
h after injury. After differentiation of the NSCs was determined using
immunohistochemistry, neurological severity scores (NSS) and rotarod test were
conducted to detect the neurological behavior. Western blot and RT-PCR as well as
ELASA were used to evaluate the expression of synaptophysin and brain-derived
neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural
recovery after NSC transplantation, BDNF knockdown in NSC was performed and
transplanted into the rats with TBI, and potential mechanism for BDNF knockdown
in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody
blockade was conducted to further confirm the effect of BDNF on neural activity.
As a result, an increasing neurological function improvement was seen in NSC
transplanted rats, which was associated with the upregulation of synaptophysin
and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF
antibody block reduced not only the level of synaptophysin but also exacerbated
neurological function deficits. Microassay analysis showed that 14 genes such as
Wnt and Gsk3-beta were downregulated after BDNF knockdown. The present data
therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC
transplantation for the treatment of TBI in adult rats.
PMID- 28421545
TI - The association between the time from oxytocin cessation during labour to
Cesarean delivery and postpartum blood loss: a retrospective cohort study.
AB - PURPOSE: Prolonged exposure to oxytocin during augmentation of labour is
associated with uterine atony and an increased risk of postpartum hemorrhage
(PPH) due to oxytocin receptor desensitization. Cessation of oxytocin infusion
during labour may facilitate recovery of oxytocin receptor function, which then
helps to restore myometrial contractility and decrease postpartum blood loss. We
examined the association between oxytocin recovery interval, i.e., the time from
discontinuing oxytocin to Cesarean delivery (CD) for labour arrest, and blood
loss. METHODS: This retrospective cohort study included women who underwent CD
for labour arrest following oxytocin-augmented labour from July 1, 2013 to July
19, 2015 at our institution. Data were collected on patient demographics, labour
and delivery characteristics, oxytocin induction and augmentation, recovery
interval, and PPH risk factors. The primary outcome was estimated blood loss
(EBL), calculated using the hematocrit variation method. RESULTS: Data on 490
women were analyzed. The mean (standard deviation) EBL was 1,341 (577) mL; the
amount of oxytocin administered during labour was 6,447 (6,868) mU, and the
oxytocin recovery interval was 99 (65) min. Every ten-minute increase in the
recovery interval was associated with a 10-mL decrease in EBL (95% confidence
interval [CI], -18 to -3; P = 0.009). Morbidly obese women had a significantly
higher EBL than those with a body mass index < 40 kg.m-2 (mean difference, 572
mL; 95% CI, 382 to 762; P < 0.001). The amount and duration of oxytocin
administered during labour, but not the oxytocin recovery interval, was
associated with the use of additional interventions to control PPH (P = 0.005).
CONCLUSION: Our study shows that an increase in the oxytocin recovery interval is
associated with a decrease in blood loss at CD in women with oxytocin augmented
labour. These data support discontinuing the oxytocin infusion as soon as the
decision is made to proceed with CD for labour arrest, particularly in morbidly
obese women.
PMID- 28421546
TI - Electronic medical record interventions and recurrent perioperative antibiotic
administration: a before-and-after study.
AB - PURPOSE: Perioperative antibiotics decrease rates of surgical-site infections.
Numerous interventions have improved administration of the first antibiotic dose;
however, failures in the administration of subsequent doses frequently occur. We
hypothesized that modifications to the electronic medical record (EMR) would
improve the administration of the second antibiotic dose and that such
improvements would be sustained over time. METHODS: This historical cohort before
and-after study of multipronged alerts in the EMR analyzed 1,348 operations on
adult patients. The operations lasted >= 240 min, utilized cefazolin as the
perioperative antibiotic-constituting 1,348 second and 182 third intraoperative
antibiotic doses-and did not involve cardiopulmonary bypass. A decision support
intervention provided dosing recommendations when clinicians documented
antibiotics. The reminder intervention displayed a continuous bar in the EMR,
starting at the time the antibiotics were dosed and ending 15 min before
subsequent doses were indicated. The primary endpoints of the study were the
change in the proportion of correctly administered second dose of cefazolin,
given in accordance with hospital guidelines in the month after implementing the
intervention, and whether any improvements declined by three to seven months
after implementation. RESULTS: Pre-intervention, 51.4% of second doses of
cefazolin were correctly administered. In the immediate post-intervention period,
68.5% were correctly administered, representing a significant absolute
improvement of 17.1% (95% confidence interval, 8.1 to 26.1; P < 0.001). Rates did
not decline over time; clinicians correctly administered 73.3% of doses in the
delayed post-intervention period (P < 0.001 vs pre-intervention). CONCLUSIONS:
These inexpensive nonintrusive interventions to the EMR provided modest lasting
improvements in proper administration of repeated doses of cefazolin. The fact
that only approximately 70% compliance was reached highlights the difficulty in
addressing this deficiency.
PMID- 28421547
TI - Effect of health literacy on adherence to osteoporosis treatment among patients
with distal radius fracture.
AB - : Patients with inadequate health literacy, those with medical comorbidities, or
those with a previous history of adverse drug events have a higher likelihood of
non-adherence to osteoporosis treatment after sustaining a distal radius
fracture. INTRODUCTION: Patients with a distal radial fracture (DRF) have a
higher risk of subsequent fractures, which provides an important opportunity to
begin treatment for osteoporosis. This study assessed the effect that health
literacy of patients suffering from a DRF has on the subsequent adherence to
osteoporosis treatment. METHODS: A total of 116 patients (female, over 50 years
of age) presenting a DRF caused by low-energy trauma were enrolled. Their health
literacy was measured using the Newest Vital Sign (NVS). Alendronate (70 mg,
orally, once weekly) was prescribed to all patients for 1 year, and adherence was
defined as taking at least 80% of the tablets for 12 months and returning for the
visit on month 12. Multivariable analyses were conducted to determine whether the
patients' clinical, demographic, and health literacy factors influenced their
adherence to osteoporosis treatment. RESULTS: About half (52%) of the
participants who sustained a DRF exhibited an inadequate health literacy, and the
rate of non-adherence to osteoporosis treatment was 38%. The rate of non
adherence for patients with inadequate literacy was significantly higher than for
those with appropriate literacy (47 vs. 29%, p = 0.04). The results of the
regression analysis indicate that limited health literacy, the presence of
comorbidities, and prior history of adverse drug events are associated with a
higher likelihood of non-adherence to osteoporosis treatment after sustaining a
DRF. CONCLUSIONS: Patients with inadequate health literacy, adverse drug events,
or medical comorbidities had higher rates of non-adherence with alendronate
treatment after sustaining a DRF. Further research is needed to show whether
improvements in patient comprehension via informational intervention in patients
with a DRF will improve adherence to osteoporosis treatment.
PMID- 28421548
TI - Erratum to: A database of body-only computer-generated pictures of women for body
image studies: Development and preliminary validation.
PMID- 28421549
TI - Extragastrointestinal stromal tumor of the inferior vena cava: a case report.
AB - Here, we present a case report of a 60-year-old female with a 5-cm tumor in the
inferior vena cava (IVC) that was positive for c-kit and CD34 expression. Thus,
we considered this to be an extragastrointestinal c-kit-positive stromal tumor
(EGIST). To the best of our knowledge, no primary EGISTs of the IVC have been
described thus far. The potential occurrence of EGISTs outside the tubular
gastrointestinal tract should be recognized in the differential diagnosis of
tumors of the great vessels. Thus, we concluded that primary c-kit-positive
stromal tumors of the IVC do indeed occur.
PMID- 28421550
TI - Distribution, genetic diversity and potential spatiotemporal scale of alien gene
flow in crop wild relatives of rice (Oryza spp.) in Colombia.
AB - BACKGROUND: Crop wild relatives (CWRs) of rice hold important traits that can
contribute to enhancing the ability of cultivated rice (Oryza sativa and O.
glaberrima) to produce higher yields, cope with the effects of climate change,
and resist attacks of pests and diseases, among others. However, the genetic
resources of these species remain dramatically understudied, putting at risk
their future availability from in situ and ex situ sources. Here we assess the
distribution of genetic diversity of the four rice CWRs known to occur in
Colombia (O. glumaepatula, O. alta, O. grandiglumis, and O. latifolia).
Furthermore, we estimated the degree of overlap between areas with suitable
habitat for cultivated and wild rice, both under current and predicted future
climate conditions to assess the potential spatiotemporal scale of potential gene
flow from GM rice to its CWRs. RESULTS: Our findings suggest that part of the
observed genetic diversity and structure, at least of the most exhaustively
sampled species, may be explained by their glacial and post-glacial range
dynamics. Furthermore, in assessing the expected impact of climate change and the
potential spatiotemporal scale of gene flow between populations of CWRs and GM
rice we find significant overlap between present and future suitable areas for
cultivated rice and its four CWRs. Climate change is expected to have relatively
limited negative effects on the rice CWRs, with three species showing
opportunities to expand their distribution ranges in the future. CONCLUSIONS:
Given (i) the sparse presence of CWR populations in protected areas (ii) the
strong suitability overlap between cultivated rice and its four CWRs; and (iii)
the complexity of managing and regulating areas to prevent alien gene flow, the
first priority should be to establish representative ex situ collections for all
CWR species, which currently do not exist. In the absence of studies under field
conditions on the scale and extent of gene flow between cultivated rice and its
Colombian CWRs, effective in situ conservation might best be achieved through
tailor-made management plans and exclusion of GM rice cultivation in areas
holding the most genetically diverse CWR populations. This may be combined with
assisted migration of populations to suitable areas where rice is unlikely to be
cultivated under current and future climate conditions.
PMID- 28421551
TI - Macrolides, Digoxin Toxicity and the Risk of Sudden Death: A Population-Based
Study.
AB - INTRODUCTION: Digoxin is commonly prescribed to elderly patients with heart
failure and atrial fibrillation, and macrolide antibiotics markedly increase the
risk of digoxin toxicity. OBJECTIVE: The aim was to determine whether, in older
patients receiving digoxin, macrolide antibiotics are associated with sudden
death. METHODS: We used a population-based, nested, case-control design from
January 1, 1994 to December 31, 2012 in a cohort of Ontario residents aged 66
years or older prescribed digoxin. The primary outcome was the risk of sudden
death within 14 days of exposure to one of three antibiotics (erythromycin,
clarithromycin, or azithromycin), relative to cefuroxime. RESULTS: Among 39,072
Ontarians who died suddenly while receiving digoxin, 586 died within 14 days of
receiving a study antibiotic. Relative to cefuroxime, we found no statistically
significant increase in the risk of sudden death following treatment with
erythromycin [adjusted odds ratio (aOR) 0.98; 95% confidence interval (CI) 0.65
1.48], clarithromycin (aOR 1.25; 95% CI 0.94-1.65), or azithromycin (aOR 1.07;
95% CI 0.75-1.53). CONCLUSION: This finding reinforces the cardiovascular safety
of macrolide antibiotics in a high-risk population.
PMID- 28421552
TI - Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule
Cell Layer.
AB - Local field potential (LFP) oscillations in the granule cell layer (GCL) of the
cerebellar cortex have been identified previously in the awake rat and monkey
during immobility. These low-frequency oscillations are thought to be generated
through local circuit interactions between Golgi cells and granule cells within
the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also
are electrically coupled through gap junctions within the GCL. Here, we tested if
gap junctions in the rat cerebellar cortex contribute to the generation of LFP
oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia,
and examined the effects of local infusion of gap junction blockers on 5-15 Hz
oscillations. Local infusion of the gap junction blockers carbenoxolone and
mefloquine resulted in significant decreases in the power of oscillations over a
30-min period, but the power of oscillations was unchanged in control experiments
following vehicle injections. In addition, infusion of gap junction blockers had
no significant effect on multi-unit activity, suggesting that the attenuation of
low-frequency oscillations was likely due to reductions in electrical coupling
rather than a decreased excitability within the granule cell layer. Our results
indicate that electrical coupling among the Golgi cell networks in the cerebellar
cortex contributes to the local circuit mechanisms that promote the occurrence of
GCL LFP slow oscillations in the anesthetized rat.
PMID- 28421553
TI - Microwave ablation of malignant renal tumours: intermediate-term results and
usefulness of RENAL and mRENAL scores for predicting outcomes and complications.
AB - The aim of this study was to evaluate intermediate-term results after microwave
ablation (MWA) of renal tumours and determine the association of RENAL and
modified RENAL (mRENAL) scores with oncological outcomes and complications. In
May 2008-September 2014, 58 patients affected by early-stage RCC (renal cell
carcinoma; T1a or T1b) were judged unsuitable for surgery and treated with
percutaneous MWA. Follow-up was performed with contrast-enhanced computed
tomography at 1, 3, 6, 12 and 24 months after the procedure. Technical success
(TS), primary technical effectiveness (PTE), secondary technical effectiveness
(STE), the local tumour progression rate (LTPR), the cancer-specific survival
rate (CSSR), disease-free survival (DFS), overall survival (OS) and safety were
recorded. All lesions were evaluated using RENAL and mRENAL scores, and
complications were assessed with RENAL scores. The TS rate was 100%, PTE was 93%,
STE was 100%, LTPR was 15.7% at 1 year, CSSR was 96.5%, DFS was 87.9% at 5 years,
and OS was 80.6%. Mean follow-up was 25.7 months (range 3-72). The mean +/-
standard deviation (SD) RENAL and mRENAL scores of all treated tumours were 6.7
+/- 2.05 (range 4-11) and 7 +/- 2.3 (range 4-12), respectively. Major
complications occurred in two (2/58) and minor complications in three patients
(3/58). Overall complications correlated significantly with RENAL scores; in
particular, E and L represent negative predictors for safety and effectiveness.
MWA is a valuable alternative for treating RCCs. The correlation with outcomes
and complications of RENAL and mRENAL scores could help to customise MWA
indications in RCC patients.
PMID- 28421554
TI - Drug Therapy in the 1990s : What Can We Expect for Cystic Fibrosis?
PMID- 28421557
TI - Cancer-Associated Anorexia and Cachexia : Implications for Drug Therapy.
AB - Anorexia and cachexia are major problems in patients with cancer. Such measures
as anticancer therapy, dietary counselling or hyperalimentation are not very
successful in reversing this phenomenon in the vast majority of cancer patients.
Thus, several drugs have been evaluated as agents to ameliorate cancer-associated
anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to
cause slight appetite stimulation in patients. A randomised clinical trial,
however, was unable to demonstrate any weight gain from this agent.
Corticosteroids are frequently used in clinical practice for appetite stimulation
in patients with advanced malignancies. Supporting this practice, 4 randomised
clinical trials showed that corticosteroid medications can stimulate the
appetites of advanced cancer patients. However, these studies were not able to
show any substantial nonfluid weight gain in treated patients.Megestrol acetate
is a progestational agent which appears to be a relatively potent appetite
stimulant. Randomised studies in advanced cancer patients have shown both
substantial appetite stimulation and improvement in the nonfluid bodyweights of
patients receiving this drug. Preliminary evidence also suggests that this drug
has antiemetic properties. Several clinical studies are currently ongoing to
determine the effect of various doses of megestrol acetate in patients with
cancer.Efforts are also ongoing to evaluate both anabolic steroids and hydrazine
sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The
preliminary nature of these investigations, however, precludes recommendations
for the use of either of these latter 2 drugs in routine clinical practice.
PMID- 28421556
TI - Recent Advances in Pharmacological Management of Hypertension in Diabetic
Patients with Nephropathy : Effects of Antihypertensive Drugs on Kidney Function
and Insulin Sensitivity.
AB - Hypertension is often seen in Type 1 and Type 2 diabetic patients, particularly
in those with nephropathy, and the progression of diabetic nephropathy is closely
related to blood pressure elevation. Thus, the effects of antihypertensive drugs
on kidney function and insulin sensitivity in diabetic patients are of great
clinical importance.Successful antihypertensive treatment has been shown to slow
the progression of diabetic nephropathy. Several results from short term studies
have suggested that angiotensin converting enzyme (ACE) inhibitors may be
advantageous over other conventional antihypertensive agents in reducing
albuminuria in both hypertensive and normotensive diabetics with microalbuminuria
or persistent proteinuria. However, the decline in glomerular filtration rate
during ACE inhibitor treatment is comparable to that during effective treatment
with conventional antihypertensive drugs in hypertensive Type 1 diabetic patients
with overt nephropathy. Whether ACE inhibitors possess a specific effect in
preventing the development of diabetic nephropathy remains to be seen in properly
designed long term studies. Although calcium antagonists may preserve kidney
function or possess a renoprotective effect in hypertensive Type 2 diabetics with
nephropathy, firm evidence supporting this contention seems to be lacking and
also requires long term evaluation.Increasing attention is being directed toward
the effect of antihypertensive drugs on insulin sensitivity in diabetic patients:
ACE inhibitors and alpha-adrenoceptor blocking agents have been shown to improve
this sensitivity. Despite the widespread involvement of calcium in hormone
secretion and action, calcium antagonists appear to have little effects on the
glucoregulatory and calcium-regulatory hormones within the drug dosages used in
clinical practice.Several clinical variables, such as the presence or absence of
hypertension, overt nephropathy and microalbuminuria, or a combination of
variables should be accounted for when evaluating critically the cumulative data
on the effects of antihypertensive drugs on kidney function and albuminuria in
the variety of diabetic patient groups. Understanding the pharmacokinetic and
pharmacodynamic characteristics of antihypertensive drugs will be of clinical
importance in diabetic patients with advanced nephropathy (glomerular filtration
rate of < 30 ml/min) and/or other complications, such as impaired gastric
motility or gastroparesis, and will thereby lead to a more rational management of
hypertension in those patients.
PMID- 28421555
TI - Pharmacological Agents Affecting Emesis : A Review (Part II).
AB - Part I of this article reviewed the pathophysiology of emesis, and its
pharmacological treatment. Drug-induced vomiting was also discussed. In the
second part of the review, other common causes of vomiting are considered.The
basis of the use of antiemetics in morning sickness and migraine is still
obscure; for the latter, serotonin 5-HT1 receptor agonists, 5-HT3 receptor
antagonists and dopamine D2 receptor antagonists are effective. For motion
sickness, control can be achieved with various antagonists of muscarinic or
histamine H1-receptors. Centrally active adrenoceptor agonists in combination
with a muscarinic antagonist or H1-receptor antagonist may offer better control
of motion sickness and its associated symptoms than either antagonist alone;
based on clinical studies, post-operative vomiting after opiate administration
appears to be controlled by blocking dopamine D2, histamine H1-or muscarinic
receptors.Radiation therapy appears to be similar to cytotoxic therapy in that
the mediators produced or released by radiation activate both peripheral and
central sites involved in the vomiting reflex. Blockade of dopamine D2 and 5-HT3
receptors may be effective.
PMID- 28421561
TI - A New Mexican Species of Orizabus Fairmaire (Coleoptera: Scarabaeidae:
Dynastinae: Pentodontini), with a Key to the Species of the Genus.
AB - A new Orizabus species is described from Chilapa de Alvarez in the state of
Guerrero (Mexico). The new species is similar to Orizabus rawlinsi Dechambre Bull
Soc Entomol Fr 98:342, 1993, which is known from the state of Oaxaca but differs
in the pygidial punctation, and the shape of the marginal pronotal bead and the
parameres. A revised identification key to Orizabus species is provided.
PMID- 28421560
TI - Acitretin : A Review of its Pharmacology and Therapeutic Use.
AB - SYNOPSIS: Acitretin (etretin), a second generation monoaromatic retinoid for use
in the treatment of severe psoriasis and other dermatoses, is the major active
metabolite of etretinate and possesses a similar therapeutic index; i.e. a
similar ratio of clinical efficacy to adverse effects. When used alone at a
maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment
of psoriasis, causing a reduction in the severity of scaling, erythema and
induration. Efficacy appears to be further enhanced by combination with psoralen
ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These
combinations reduce the time to lesion clearance and reduce the total radiation
dose, improving overall safety. Comparative studies have confirmed the
equivalence of acitretin and etretinate with regard to efficacy and toxicity.
Adverse reactions are dose-related and generally typical of hypervitaminosis A.
Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous
membranes are particularly prevalent. Hypertriglyceridaemia and elevation of
cholesterol levels also occur. Examination of the pharmacokinetic profile of
acitretin reveals its main advantage over etretinate. Acitretin is less
lipophilic than etretinate, and its lack of sequestration into 'deep' fatty
storage sites is reflected in a comparatively short terminal elimination half
life of 50 to 60 hours, compared with 120 days for etretinate. Due to its
teratogenic potential, acitretin is strictly contraindicated in women of
childbearing potential unless effective contraceptive measures are employed.
Etretinate has been identified in plasma samples of some patients treated with
acitretin. Thus, acetretin has an established place in the treatment of
keratinising disorders, although its use in women of child-bearing potential must
be accompanied by effective contraceptive measures, with a further 2-year
contraceptive period after therapy completion. PHARMACODYNAMIC PROPERTIES:
Investigation of the pharmacodynamic properties of acitretin has been restricted
to some extent by the lack of a suitable experimental model. While in vitro
results using normal human skin fibroblasts have been conflicting, acitretin
generally modulates cell proliferation in cultures from hyperproliferative
conditions such as psoriasis or neoplasia, and inhibits epidermal cell growth and
differentiation. Acitretin also inhibits chemically induced hyperplasia, and
causes regression or inhibits further growth and development of a number of
established or transplantable carcinoma cell lines. The mechanism of action of
acitretin in hyperproliferative disorders has yet to be fully elucidated;
however, there appear to be a number of cellular effects. Target receptor site
candidates include the cellular retinoic acid binding protein (CRABP), the
epidermal growth factor (EGF) receptor, and retinoic acid nuclear receptors
(RARs). Acitretin binds competitively to CRABP, a protein present in high
concentrations in psoriatic plaques, and induces a marked elevation of CRABP
levels in normal epidermis. However, 13-cis-acitretin does not bind to CRABP and
acitretin may act via activation of RARs following conversion to a substance
which binds to these receptors. In addition, the EGF receptor may be involved
since acitretin has been found to influence its normal modulation of cell growth
in both normal fibroblasts and squamous carcinoma cell lines. Cyclic adenosine
monophosphate (cAMP)-dependent protein kinases and ornithine decarboxylase are
probable mediators of the clinical response. In addition, acitretin demonstrates
immunomodulatory and anti-inflammatory effects. It is hypothesised that the
mechanisms entail inhibition of polymorphonuclear leucocyte accumulation in the
stratum corneum, inhibition of lymphocytic blastogenesis by mitogens and
stimulation of T cell-mediated cytotoxicity. PHARMACOKINETIC STUDIES: Following
oral administration of the drug to patients with psoriasis, peak plasma acitretin
concentrations range from 98 to 526 ug/L and are reached approximately 1.9 hours
after a single 40mg dose. Acitretin is widely distributed in the body and
systemic bioavailability is approximately 60%. It is extensively bound to albumin
and has a high affinity for CRABP. Less than 5% of acitretin is bound to
lipoproteins and this is reflected in its comparative lack of sequestration into
fatty 'deep' storage sites and its short terminal elimination half-life relative
to etretinate. Multiple dose studies have indicated an elimination half-life of
50 to 60 hours, and neither acitretin nor its isomeric counterpart, 13-cis
acitretin, is detectable in plasma 3 to 4 weeks after cessation of long term
therapy. Isomeric interconversion is prevalent following oral administration of
acitretin: mean maximum plasma concentrations of the 13-cis-isomeric metabolite
are lower and occur slightly later than with acitretin. Plasma trough
concentrations of this metabolite following long term administration of acitretin
are about 5 times higher than those of the parent drug and the terminal
elimination half-life is about 15 times longer. Acitretin is excreted
predominantly via the renal and hepatic routes, as glucuronides in bile or as
products with shortened side chains in urine. In blood, 13-cis-acitretin and 3
other metabolites have been identified. Liquid chromatography/mass spectroscopy
has identified etretinate in plasma samples of some patients treated with
acitretin. The results obtained so far are of concern with regard to a potential
teratogenic effect in female patients. Therefore, an increase in the post therapy
contraception period to 2 years instead of the 2 months previously advocated is
appropriate until clarification of these recent results have been obtained.
THERAPEUTIC EFFICACY: Trials with an initial double-blind phase and a subsequent
noncomparative phase of up to 6 months duration have demonstrated the efficacy of
orally administered acitretin (generally 25 to 75 mg/day) in the treatment of
severe psoriasis. Variants of psoriasis vulgaris are notably susceptible to
treatment and acitretin also appears to be effective against severe forms of
pustular and erythrodermic psoriasis. Preliminary studies in small patient
populations and a number of individual case reports suggest that acitretin, 30 to
50 mg/day, is beneficial in a variety of other cutaneous disorders including
Darier's disease, lupus erythematosus and severe recessive x-linked ichthyosis.
The rarity of these conditions prevents adequate extensive trials. Double
blinding in placebo-controlled trials is difficult to maintain due to the
ubiquitous and distinctive nature of acitretin-induced adverse effects. However,
double-blinding strategies have been used effectively in studies in which a dose
finding phase preceded a longer term noncomparative phase. Subjective assessments
have revealed good to excellent (? 50%) clearance of severe psoriasis in > 75% of
patients: the severity of scaling, erythema and epidermal induration, and the
percentage of body surface involvement, are reduced. Comparative studies in
patients with psoriasis indicate that acitretin is comparable with etretinate in
terms of therapeutic efficacy and adverse effects. When acitretin is combined
with psoralen-ultraviolet A photochemotherapy (PUVA), clinical efficacy is
improved, as evidenced by a higher complete remission rate and a reduced time to
clearance of psoriasis. Total irradiation requirement is also reduced. Similar
results are also achieved when acitretin is combined with ultraviolet B
irradiation. ADVERSE EFFECTS: Acitretin therapy has distinctive adverse effects
generally typical of hypervitaminosis A. While the incidence of mucocutaneous
clinical adverse effects is high, their severity does not usually necessitate
withdrawal of therapy, and they are completely reversed on cessation of
treatment. Adverse effects are usually dose-related, although alopecia is also
dependent on the duration of therapy. Mucocutaneous reactions are most common -
drying of mucous membranes of the eyes, nose and lips, and cheilitis occurs in
nearly all patients. Other clinical symptoms include alopecia, desquamation of
the skin, pruritus and 'sticky' skin. Changes in the lipid profile are often
observed. Hypertriglyceridaemia occurs in 35% of patients treated with acitretin
50 mg/day, but increases in serum cholesterol are less frequently reported. Liver
enzyme levels are also adversely affected, hepatitis has been reported and
acitretin therapy may have an adverse effect on bone. As with etretinate,
acitretin is a potent teratogen. DOSAGE AND ADMINISTRATION: Initial acitretin
dosage has usually ranged from 10 to 75 mg/day orally. After a few weeks, the
dose should be individually adjusted to obtain optimum therapeutic response with
tolerable adverse effects. Maintenance doses in such trials have ranged from 30
to 50 mg/day. Some authorities advocate low-dose therapy initially followed by a
progressive dosage increase. Because of its potent teratogenicity and the
detection of etretinate in patients treated with acitretin, the drug is
contraindicated in women of childbearing potential unless effective contraceptive
measures are adopted. It is essential that pregnancy be avoided for a full 2
years after therapy finishes, instead of the 2 months previously advocated.
PMID- 28421562
TI - Prevention of Bacterial Biofilm Formation on Soft Contact Lenses Using Natural
Compounds.
AB - PURPOSE: In eye care field, contact lenses (CL) have a great impact on improving
vision, but their use can be limited by ocular infection. CL- associated
infections can be reduced by good attention to CL storage case practice. CL-care
solutions should be able to control microbial growth on CL. The aim of the study
was to evaluate and compare the efficacy of CL-care solutions (found in Egyptian
market) with some natural compounds in removal and inhibition of bacterial
biofilm formed on soft CL. Clinical isolates were recovered from patients having
conjunctivitis from Benha University Hospital and identified microbiologically.
Quantification of biofilm was done using microtiter plate assay. Three
multipurpose CL-care solutions were examined for their ability to remove and
inhibit biofilm. Also four natural extracts having antibacterial activity and are
safe on eye were tested for their anti-biofilm activity. RESULTS: The major
bacterial isolates from eye infections were Pseudomonas aeruginosa (36%) and
Staphylococcus spp. (37.8%). Only 33.3% of isolates showed ability to produce
weak to moderate biofilm. The tested multi-purpose CL-care solutions showed
moderate ability to remove preformed biofilm. Among the tested natural compounds,
Calendula officinalis and Buddleja salviifolia extracts showed an excellent
efficacy in inhibition of biofilm and also removal of preformed biofilm.
CONCLUSION: This study demonstrated that isolates from infected eye and CL-cases
showed weak to moderate biofilm formation. Calendula officinalis and Buddleja
salviifolia extracts showed excellent effect on inhibition and removal of
biofilm, these extracts could be added into CL-care solutions which could
markedly reduce eye-infections during CL-wear.
PMID- 28421563
TI - The current utilization and perceptions of prescription drug monitoring programs
among emergency medicine providers in Florida.
AB - BACKGROUND: Pain is among the most commonly treated symptoms in the emergency
department, and opioids are commonly prescribed from the emergency department to
treat moderate to severe pain. Prescription drug monitoring programs (PDMP) can
be used to assist physicians identify individuals at increased risk to misuse or
abuse opioids. While the use of the PDMP has been shown useful among clinicians,
in the past, utilization of the PDMP has been less than optimal. The objective of
this study was to assess the current utilization and perceptions of the
prescription drug monitoring program among emergency medicine providers in
Florida. METHODS: A survey assessing the utilization and perception of Florida's
prescription drug monitoring program was distributed to emergency medicine
providers in Florida over a 5 week period. Attending physicians, physicians in
training, and extenders from a variety of practice types were assessed. RESULTS:
A total of 88 surveys were completed. Over two thirds (67%) of the respondents
were male. The majority of respondents were attending physicians (62%), 13 (14%)
were residents, and 21 (23%) were extenders. Nearly all (99%) were aware of
Electronic-Florida Online Reporting of Controlled Substance Evaluation Program
(EFORCSE) and 84% had registered accounts. More than 2/3 (73%) reported feeling
pressured to prescribe opioids, and 70% reported receiving no formal education on
identifying individuals at increased risk of opioid misuse. Approximately half
(51%) reported that they used EFORCSE only when they suspect the patient may
misuse the medication, 21% reported that they rarely used EFORCSE, and only 3%
reported using PDMP every time that they prescribed opioids. Residents used PDMP
less frequently than extenders and attending physicians. The most common barriers
associated with PDMP use were related to access. CONCLUSIONS: Although most
providers reported that they were aware of their states' PDMP, utilization of the
PDMP among emergency medicine providers in Florida remains low. Low utilization
was associated with barriers to access. If further enhancements to PDMPs can be
made to improve accessibility, then rates of PDMP utilization may increase.
PMID- 28421558
TI - Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review
of its Pharmacological Properties and Prospective Role in the Management of
Myelosuppression.
AB - SYNOPSIS: Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF)
is a polypeptide hormone produced through recombinant DNA technologies in
glycosylated (yeast or mammalian expression systems) or nonglycosylated
(Escherichia coli expression system) form. It is a multilineage haematopoietin
which stimulates proliferation and differentiation of bone marrow myeloid
progenitors and increases peripheral white blood cell counts when administered
systemically. Treatment is generally well tolerated, although mild to moderate
flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be
problematic in occasional patients. rGM-CSF accelerates recovery of peripheral
neutrophil counts after bone marrow transplantation, and results of a placebo
controlled randomised trial correlate this with reduced infectious episodes and
shortened length of hospitalisation in patients with lymphoid malignancies. A
substantial number of patients with graft failure after bone marrow
transplantation also respond to rGM-CSF. The duration of myelosuppression
secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which
has permitted investigation of antineoplastic dose-intensity escalation. In some
haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia
secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically
useful increases in peripheral blood granulocyte counts, although the effect is
generally not sustained after drug withdrawal. The potential for rGM-CSF to
stimulate proliferation of the abnormal clone in myelodysplasia and in acute
myelogenous leukaemia following induction therapy is of concern. Available data
suggest, however, that with appropriate monitoring and exclusion of high-risk
patients this serious potential risk can be avoided, and that myelopoiesis is
enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating
factors are a new therapeutic modality; hence many aspects of their use remain to
be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has
major potential in the management of myelosuppression secondary to cytoreductive
therapy with or without bone marrow transplantation, and in amelioration of
disturbed myelopoiesis. It represents an important application of biotechnology
to a difficult area of therapeutics. PHARMACOLOGICAL PROPERTIES: Endogenous GM
CSF is produced by T-lymphocytes, macrophages, fibroblasts and endothelial cells,
and participates both in the complex regulation of blood cell formation and in
activation of mature leucocytes. It is a polypeptide which is variably
glycosylated in its native state although the carbohydrate content is not
essential for its biological effects, and the 3 available recombinant forms
(which differ in extent of glycosylation) are similarly active in vivo.
Proliferative activity and priming of mature cells are manifest at similar
picomolar concentrations of GM-CSF, and it is the programming of the cell which
appears to determine the response to binding of GM-CSF to its cell surface
receptor. In concert with other colony-stimulating factors, GM-CSF facilitates
lineage commitment and subsequently supports or amplifies the clonogenic activity
of lineage-restricted factors, with the strongest effect seen on the granulocyte
macrophage lineage. A biphasic response was seen when rGM-CSF was administered in
doses up to 1000 ug/m2/day or 60 ug/kg/day by subcutaneous or intravenous routes
in phase I/II trials. Peripheral blood leucocyte counts decreased rapidly and
profoundly secondary to sequestration within the lungs. Re-entry of these cells
into the circulation restores counts to baseline in 2 to 4 hours and thereafter
an increase in the proliferative fraction of haematopoietic cells in bone marrow
probably accounts for the progressive rise in the number of neutrophils,
eosinophils and monocytes. This effect is dose-proportional. GM-CSF stimulates
proliferation of leukaemic progenitors from patients with acute myeloid leukaemia
without stimulating differentiation. In contrast, the abnormal clone from
myelodysplastic patients can be induced with GM-CSF to differentiate in vitro
although karyotype anomalies persist. In vitro studies suggest that stimulation
of nonhaematological cancer cells at physiological concentrations of GM-CSF is
unlikely. The priming effects of GM-CSF on mature leucocytes which include
increased expression of other cytokines, secretion of granule contents,
augmentation of antigen presentation, altered chemotaxis, and enhanced
phagocytosis, oxidative metabolism and antibody dependent cell-mediated
cytotoxicity probably serve to increase the host response to infection.
Administration of murine rGM-CSF to mice injected with lethal inocula of, for
example, Pseudomonas aeruginosa improved their survival relative to controls.
There are several reports of refractory infection in seriously ill neutropenic
patients resolving after addition of rGM-CSF to ongoing antimicrobial therapy and
subsequent neutrophil recovery; however, the role of rGM-CSF in management of
established infection in patients with neutropenia remains to be more thoroughly
investigated. The pharmacokinetic properties of rGM-CSF depend on the route of
administration. After intravenous administration, serum levels decline rapidly
with a half-life of distribution (t1/2alpha) of 5 to 15 minutes and half-life of
elimination (t1/2beta) of 1.5 to 2 hours. Maximum serum concentrations are
reached 2 hours after subcutaneous injection, then decline with a t1/2beta of 3
hours. Serum levels of rGM-CSF increase with dose and a proposed therapeutic
target level of 1 ug/L is maintained for 8 to 22 and 16 hours after
administration of 15 ug/kg of rGM-CSF by intravenous bolus and subcutaneous
injection, respectively. THERAPEUTIC USE: The correlation between duration and
severity of neutropenia and incidence of serious infection is well established.
Administration of rGM-CSF to bone marrow transplant recipients is aimed at
reducing morbidity in the early post-transplant period by shortening the duration
of agranulocytosis. Intravenous administration of rGM-CSF up to 16 ug/kg/day
(approximately 640 ug/m2/day) is well tolerated, and when begun within 24 hours
of autologous marrow infusion produces the earlier appearance of > 0.5 * 109/L
neutrophils in the peripheral circulation as compared with historical controls.
Early studies indicate that treated patients have a lower incidence of culture
proven bacteraemia, and recent reports, some preliminary, of placebo-controlled
and randomised trials confirm that patients with nonHodgkin's lymphoma or acute
lymphocytic leukaemia who receive rGM-CSF 250 ug/m2 by daily 2-hour infusion for
21 days or more post transplantation, have significant reductions in duration of
infectious episodes, antibiotic administration and hospitalisation. More limited
data support a similar acceleration of neutrophil recovery in allogeneic bone
marrow transplant recipients treated with rGM-CSF, with no apparent effect on the
incidence or severity of graft-versus-host disease. rGM-CSF is less effective in
patients in whom progenitor cell numbers are reduced by chemical purging of the
marrow whether administered immediately after marrow infusion or when used as
salvage therapy in patients with graft failure. A substantial proportion of
patients with failure of autologous or allogeneic bone marrow grafts respond to
prompt administration of rGM-CSF after diagnosis of graft failure, with an
increase in absolute neutrophil count and bone marrow cellularity. In 1 study of
37 such patients, overall survival was significantly improved compared with
historical controls. rGM-CSF increases the number of progenitor cells in
peripheral circulation and, either alone or in combination with cyclophosphamide,
facilitates the harvest of stem cells by apheresis for subsequent
transplantation. Similar to the effect seen after myeloablative therapy and
marrow transplantation, rGM-CSF accelerates neutrophil recovery following
cytoreductive chemotherapy in patients with nonhaematological malignancies. Less
frequent and less severe mucositis was also observed in rGM-CSF-treated versus
control patients in several studies. Importantly, adjunctive use of rGM-CSF
facilitated delivery of planned cycles of high or escalated doses of
antineoplastic drugs although the value of such chemotherapy regimens remains to
be proven. There has been no evidence to date that rGM-CSF increases the rate of
relapse of patients with haematological malignancies when administered after
myeloablative therapy and bone marrow transplantation or, in patients with acute
myelogenous leukaemia, after induction therapy. Use of rGM-CSF to recruit
quiescent leukaemic blast cells into S phase prior to chemotherapy is under
investigation. rGM-CSF has been investigated in various disorders of
haematopoiesis. A substantial number of adults and children with refractory
aplastic anaemia respond to treatment with increases in bone marrow cellularity
and peripheral blood granulocyte count; however, the response is generally not
sustained after withdrawal of rGM-CSF. Elevation of neutrophil counts may not
occur in patients with long-standing and severe aplasia; however, beneficial
stimulation of macrophage function may still occur. Generally, rGM-CSF induces
eosinophilia without correcting the neutropenia in patients with congenital
neutropenic conditions. In myelodysplasia, rGM-CSF is capable of increasing the
neutrophil count in a proportion of patients for the duration of administration.
Caution is appropriate in administering this drug to patients with high (> 14%
blasts) initial leukaemic burdens or with chronic myelomonocytic leukaemia in
view of the potential for rGM-CSF to stimulate the leukaemic clone and
precipitate acute leukaemia. Despite this concern, encouraging preliminary
results from a trial with rGM-CSF (3 ug/kg/day by subcutaneous injection) and
observation-only treatment groups suggest that, after > 6 months, the rate of
transformation to acute leukaemia is similar in both groups but that rGM-CSF
recipients have a sustained increase in neutrophil counts and an associated
reduction in infection rate. rGM-CSF 1 to 5 ug/kg/day by subcutaneous injection
ameliorates leucopenia associated with HIV infection and corrects zidovudine
(azidothymidine)-induced neutropenia without affecting the disease course as
determined by p24 antigen levels, CD4: CD8 ratios and recovery of HIV from
mononuclear cells. Similar dosages ameliorate myelosuppression induced by
ganciclovir in the treatment of AIDS-associated cytomegalovirus retinitis and by
the combination of zidovudine and interferon-alpha in treating Kaposi's sarcoma.
A trilineage response to rGM-CSF has been seen occasionally (e.g. some children
with aplastic anaemia and some patients with myelodysplasia). Disease-or drug
induced anaemia or thrombocytopenia is generally not improved; however, both
significant increases and decreases in platelet count have been reported, and the
effect of rGM-CSF on megakaryocytosis and splenic phagocyte function require
clarification. The combination of rGM-CSF with other recombinant colony
stimulating factors to expand the lineages stimulated is an exciting future
possibility. TOLERABILITY: At clinically useful dosages rGM-CSF is generally well
tolerated. Limited comparison with placebo suggests that the type and incidence
of adverse reactions reported are generally similar in both groups with the
possible exception of slightly higher incidences of diarrhoea, asthenia, rash and
malaise. However, reports from noncomparative and open-label trials indicate that
mild to moderate flu-like symptoms (myalgias, bone pain, fatigue and headache)
are common with rGM-CSF. Management of patients in whom this agent is indicated
may be complicated by rGM-CSF-induced fever and, rarely, by a capillary leak
syndrome causing fluid retention and potentially peripheral oedema, pericardial
or pleural effusions which necessitate drug withdrawal. Also reported are rash
(particularly at sites of subcutaneous injection), and occasional incidents of
central venous catheter thrombosis. The occasional report of respiratory distress
has led to the recommendation that respiratory symptoms be monitored and caution
exercised in patients with preexisting lung disease. DOSAGE AND ADMINISTRATION:
The approved (USA) dosage of yeast-derived rGM-CSF (sargramostim) for myeloid
reconstitution after autologous bone marrow transplantation is 250 ug/m2 by daily
2-hour intravenous infusions, beginning 2 to 4 hours after marrow infusion and
continued for 21 days. For management of bone marrow transplantation failure or
delayed engraftment, the approved (USA) dosage of yeast-derived rGM-CSF is 250
ug/m2/day by 2-hour intravenous infusion. Treatment should be continued for 14
days and, if clinically indicated, may be repeated after 7 days off therapy. A
third 14-day course of rGM-CSF at the increased dosage of 500 ug/m2/day by 2-hour
infusion may be administered after a further 7 days off therapy. Further dose
escalation in non-responding patients is unlikely to be of benefit. rGM-CSF has
also been successfully administered by continuous intravenous infusion and by
subcutaneous injection, including self-administration of long term therapy by the
subcutaneous route. The optimal route for administration, dose and duration of
therapy for indications other than autologous bone marrow transplantation and
failure or delay of engraftment have not been established.
PMID- 28421564
TI - Erratum to: Long-term safety and efficacy of Omnitrope(r) in adults with growth
hormone deficiency: Italian interim analysis of the PATRO Adults study.
PMID- 28421565
TI - Iron homeostasis in inflammation: a single centre prospective observational study
in medical inpatients.
AB - AIMS OF THE STUDY: We aimed to assess a potential association of iron status with
mortality and morbidity of inpatients with systemic inflammation. METHODS: This
was a single centre prospective observational study. From April 2014 to October
2014, all consecutive medical inpatients aged >=18 years with a C-reactive
protein value >5 mg/l on hospital admission were eligible for the study. We
excluded pregnant women and patients with terminal renal insufficiency or past
allogeneic stem cell transplantation. For all patients, a complete set of serum
iron parameters was obtained on hospital admission. In the final analysis, the in
hospital all-cause mortality and several morbidity measures (length of stay,
number of secondary diagnoses and Charlson Comorbidity Index) were compared
between four distinct iron status groups: patients having iron deficiency
anaemia, iron deficiency without anaemia, anaemia without iron deficiency, and
normal iron status. Iron deficiency was quantifies as the serum transferrin
receptor / ferritin index, with a cut-off level of 1.5. RESULTS: A total of 438
patients were included in the final analysis. Patients with iron deficiency had a
higher in-hospital mortality than patients with iron deficiency anaemia, anaemia
without iron deficiency, or normal iron status (6% vs 1%, 5%, and 1%,
respectively; p = 0.042). Patients with iron deficiency anaemia had a higher
number of secondary diagnoses (mean 8.4; standard deviation 4.2) and a higher
Charlson Comorbidity Index (mean 1.8; standard deviation 1.9) than patients with
iron deficiency, anaemia without iron deficiency, or normal iron status (p <0.001
and p <0.001, respectively). The median length of stay did not differ
significantly between the iron status groups (p = 0.080). CONCLUSIONS: In our
study population, iron status was significantly associated with mortality and
morbidity. Further studies are required to assess the pathophysiological and
clinical effects of an altered iron metabolism and iron substitution therapies in
inflammation.
PMID- 28421566
TI - Precision global health in the digital age.
AB - Precision global health is an approach similar to precision medicine, which
facilitates, through innovation and technology, better targeting of public health
interventions on a global scale, for the purpose of maximising their
effectiveness and relevance. Illustrative examples include: the use of remote
sensing data to fight vector-borne diseases; large databases of genomic sequences
of foodborne pathogens helping to identify origins of outbreaks; social networks
and internet search engines for tracking communicable diseases; cell phone data
in humanitarian actions; drones to deliver healthcare services in remote and
secluded areas. Open science and data sharing platforms are proposed for
fostering international research programmes under fair, ethical and respectful
conditions. Innovative education, such as massive open online courses or serious
games, can promote wider access to training in public health and improving health
literacy. The world is moving towards learning healthcare systems. Professionals
are equipped with data collection and decision support devices. They share
information, which are complemented by external sources, and analysed in real
time using machine learning techniques. They allow for the early detection of
anomalies, and eventually guide appropriate public health interventions. This
article shows how information-driven approaches, enabled by digital technologies,
can help improving global health with greater equity.
PMID- 28421567
TI - Early biomarker response and patient preferences to oral and intramuscular
vitamin B12 substitution in primary care: a randomised parallel-group trial.
AB - BACKGROUND: Vitamin B12 (VB12) deficiency can be treated with oral high-dose
substitution or intramuscular (i.m.) injection of VB12. Whenever alternative
routes of administration exist, patient preferences should be considered when
choosing the treatment. We aimed to assess outpatient preferences towards oral or
IM VB12 substitution and confirm noninferiority of early biomarker response with
oral treatment, in a typical primary care population. METHODS: Prospective
randomised nonblinded parallel-group trial. Patients were recruited by their
general practitioner and randomly assigned to oral or IM treatment. Group O-oral
was given 28 tablets of 1000 ug cyanocobalamin in a monthly punch card fitted
with an electronic monitoring system. Group I-IM received four, weekly injections
of 1000 ug hydroxocobalamin. Blood samples were drawn before the first
administration and after 1, 2 and 4 weeks of treatment, and analysed for VB12,
holotranscobalamin (HoloTc), homocysteine (Hcy) and methylmalonic acid (MMA). For
group O-oral, treatment adher-ence and percentage of days with ?2 dosing events
were calcu-lated. Before and after 28 days of treatment, patients were asked to
fill in a questionnaire about their preference for the therapy options and
associated factors. RESULTS: Between November 2013 and December 2015, 37 patients
(age: 49.5 +/- 18.5 years; women: 60.5%) were recruited for oral (19) or IM (18)
treatment. Baseline values with 95% confidence intervals for serum VB12, HoloTc,
Hcy and MMA were 158 pmol/l [145-172], 49.0 pmol/l [40.4-57.5], 14.8 umol/l [12.0
17.7] and 304 nmol/l [219-390], respective-ly, in group O-oral and 164 pmol/l
[154-174], 50.1 pmol/l [38.7-61.6], 13.0 umol/l [11.0-15.1] and 321 nmol/l [215
427], respectively, in group I-IM (not significant). After 1 month of treatment,
levels of VB12 and HoloTc showed a significant increase compared with baseline
(group O-oral: VB12 354 pmol/l [298-410] and HoloTc 156 pmol/l [116-196]; group I
IM: VB12 2796 pmol/l [1277-4314] and HoloTc 1269 pmol/l [103-2435]). Hcy and MMA
levels showed a significant decrease compared with baseline (group O-oral: Hcy
13.8 umol/l [10.7-16.8] and MMA 168 nmol/l [134-202]; group I-IM: Hcy 8.5 umol/l
[7.1-9.8] and MMA 156 nmol/l [121-190]). HoloTc and MMA levels were normalised in
all patients after 4 weeks of treatment, whereas normalisation of VB12 and Hcy
was reached by all patients in group I-IM only. Response of VB12, HoloTc and Hcy
was more pronounced in group I-IM (p <0.01) and the primary hypothesis that oral
VB12 treatment would be noninfe-rior to IM treatment was rejected. Average
adherence to thera-py was 99.6 +/- 1.1% and days with ?2 dosing events reached
5.6%. Before randomisation, preference was in favour of oral treatment (45.9%, n
= 17) over IM administration (21.6%, n = 8). Twelve patients (32.4%) had no
preference. Nine (24.3%) patients changed their preference after treatment.
Patients who obtained their preferred route of administration main-tained their
preference in the case of oral treatment and changed their preference after IM
treatment. CONCLUSIONS: Differences in VB12 levels between groups were higher
than expected. Therefore, noninferiority of oral treat-ment had to be rejected.
However, normalisation of HoloTc and MMA was reached by all patients after a 1
month treatment period. The clinical benefit of the exaggerated biomarker re
sponse after IM treatment within a typical primary care popula-tion is
questionable. Midterm biomarker effects and patient preferences should be
considered when a therapeutic scheme is chosen. Initial rating in favour of
either IM or oral therapy can change over time and justifies repeated re
evaluation of patient preferences. (ClinicalTrials.gov ID NCT01832129).
PMID- 28421568
TI - Prions, prionoid complexes and amyloids: the bad, the good and something in
between.
AB - Prions are infectious agents causing transmissible spongiform encephalopathies in
humans and animals. These protein-based particles template conformational changes
in a host-encoded prion protein to an insoluble self-like conformation. Prions
are also present in yeast, where they support protein-based epigenetic
inheritance. There is emerging evidence that prion-like (prionoid) particles can
support a variety of pathological and beneficial functions. The recent data on
the prionoid spread of other pathological amyloids are discussed in light of
differences between prions and prion-like aggregates. On the other hand, prion
like action has also been found to support important functions such as memory,
and amyloids were shown to have a variety of physiological roles from storage to
scaffolding in simple organisms and in humans. Higher-order protein complexes
play important roles in signalling. Many death-fold domains can polymerise upon
nucleation to enhance sensitivity and induce a robust response. Although these
polymers are structurally different from amyloids, some of them are characterised
by prionoid activities, such as intercellular spread. The initial activation of
these complexes is vital for organismal health, whereas prolonged activation
leading to unresolved inflammation underlies autoinflammatory and other diseases.
Prionoid complexes play important roles far beyond prion diseases and
neurodegeneration.
PMID- 28421569
TI - Two-step procedure for complicated appendicitis with perityphlitic abscess
formation.
AB - PRINCIPLES: Optimal management of perforated appendicitis with perityphlitic
phlegmon or abscess formation is controversial. The aim of the study was to
assess the outcome after a two-step procedure to treat patients with
perityphlitic abscess formation. METHODS: We retrospectively assessed
prospectively collected data from a single-centre database that included adult
patients who had appendicitis and perityphlitic abscess (>=3 cm) but no
generalised peritonitis, and were treated in 2007-2015. Patients underwent a two
step procedure that comprised antibiotic treatment and drainage when technically
feasible (step 1) followed by interval appendectomy (step 2). We evaluated
treatment modalities, complications and outcomes. RESULTS: Out of a total of 1480
patients with appendicitis, 15 patients presented with perityphlitic abscess. In
addition to antibiotic treatment, computed tomography-guided drainage was
performed in 12 of these cases. Step 1 and 2 hospital stays were (median, range)
7 days (5-14 days) and 2 days (2-12 days), respectively. One patient's abscess
recurred after 2 months, associated with new onset appendicitis and perforation.
Another patient underwent reoperation after interval appendectomy for suspected
postoperative peritonitis. CONCLUSION: This two-step procedure for appendicitis
with appendicular abscess was highly successful (100%) with a low rate of
complications (13%). In the view of a potentially increased rate of appendicular
neoplasm in combination with abscess formation, the role of interval appendectomy
has to be evaluated in larger trials.
PMID- 28421570
TI - "Real world" experience in Cardiac Resynchronization Therapy at a Swiss Tertiary
Care Center.
AB - BACKGROUND: Based on a reduction in morbidity and mortality, cardiac
resynchronisation therapy (CRT) has evolved as a standard therapy for patients
with advanced heart failure. OBJECTIVE: To provide insight into patient
demographics, safety, echocardiographic remodelling and long-term follow-up of
patients treated with CRT in a "real-world" setting at a Swiss tertiary care
centre. METHODS: Patients implanted with a CRT device at the University Heart
Centre Zurich between 2000 and 2015 were consecutively enrolled. Initial clinical
and echocardiographic therapy response as well as long-term follow-up for
mortality (defined as all-cause death, heart transplantation or ventricular
assist device implantation) and hospitalisation for heart failure were assessed.
RESULTS: A total of 418 patients with a median age of 66 years at the time of CRT
implantation (78% male) were enrolled. Serious peri-interventional complications
(from the time of implantation up to 14 days thereafter) were rare and included
systemic infections in 2.4%, pneumothorax in 3.3% and haematoma requiring
revision in 2.2% of cases. Overall, the Kaplan-Meier estimate for 5-year freedom
from the composite endpoint (hospitalisation for heart failure or mortality) was
55.8%; the Kaplan-Meier estimate for 5-year freedom from mortality was 64.1%. CRT
was associated with a significant symptomatic improvement and left ventricular
reverse remodelling. Overall, 3.9% of patients did not respond to cardiac
resynchronisation therapy (decline in left ventricular ejection fraction [LVEF]
>5%), whereas 35.1% experienced neither a continued decline nor a relevant
improvement of LVEF (+/-5%). In the remaining 61% of patients we observed an
improvement in LVEF of more than 5%. Forty percent and 31% of patients were super
responders, defined as an absolute LVEF improvement of ?10% and by a relative
reduction of left ventricular end-diastolic volume index by 20% or more. Super
response to CRT was associated with a significant benefit in terms of survival
and rehospitalisation rates. CONCLUSION: Our data are consistent with large
multicentre trials and indicate that CRT is similarly effective in a real-world
setting in Switzerland.
PMID- 28421571
TI - [Lessons from historic psychiatric records regarding the effects of
antipsychotics?]
PMID- 28421572
TI - [Suicidal behaviour among prisoners: prevalence and association with
psychological distress in Flemish prisons].
AB - BACKGROUND: Internationally, the prevalence of suicidal behaviour (suicidal
ideation, suicide plan and attempted suicide) is significantly elevated among
prisoners compared to the community at large. AIM: To estimate the prevalence of
suicidal behaviour among prisoners in the Flanders region of Belgium, to identify
differences according to gender and custodial status, and to examine the
association of recent suicidal ideation and suicide plan with psychological
distress. METHOD: We performed a cross-sectional survey using a representative
sample of 1,326 prisoners, randomly selected from 15 Flemish prisons. RESULTS:
During their lifetime, an estimated 44.4% of prisoners in Flanders reported
suicidal ideation, 30.2% made a suicide plan, and one-fifth (21.8%) attempted
suicide at least once. Past-year suicidal ideation in prison was endorsed by one
fourth (24.9%) of all prisoners, and 14.3% made a recent suicidal plan during
their current incarceration. Approximately one in ten prisoners (9.5%) attempted
suicide while in prison. Recent suicidal ideation and suicide plan were
significantly associated with high levels of psychological distress. Generally,
female prisoners reported significant higher levels of suicidal behaviour than
men, while differences according to custodial status were less unequivocal.
CONCLUSION: Corroborating international research findings, high rates of suicidal
behaviour were identified among prisoners in Flanders, compared to the general
population. Not only is suicidal behaviour a significant risk factor for suicide,
it is also important in its own right as an indicator of profound psychological
distress. Suicidal behaviour should therefore be an important target for
prevention and intervention in this at-risk population.
PMID- 28421573
TI - [Forensic (flexible) assertive community treatment: client characteristics and
treatment outcomes].
AB - BACKGROUND: (Flexible) Assertive community treatment ((f)act) is applied
increasingly to forensic psychiatric clients. However, evidence about the
effectiveness of forensic (f)act is scanty. AIM: To investigate to what extent
(subgroups of) clients receiving care from forensic (f)act teams show, after a
year, changes in their social and psychological functioning and are subjected to
fewer justicial outcome measures. METHOD: Between 2009 and 2011, eight forensic
(f)act teams collected, at two measurement moments separated by an average of 12
months, data relating to client characteristics and outcomes of care. The study
involved 202 clients. RESULTS: After a year clients showed significant
improvements in psychological and social functioning, and had fewer
confrontations with the police and the law. They were detained less often and for
shorter periods and were considered to be less likely to reoffend. The number of
admissions to mental health care and to addiction and forensic care remained
constant. CONCLUSION: Clients with a psychiatric disorder and likely to display
criminal behaviour showed improvement while being treated by forensic (f)act
teams. Further research is needed to prove whether forensic (f)act treatment will
have the desired effects in the longer term and will enjoy the status of being
regarded as evidence based practice.
PMID- 28421574
TI - [Compulsory treatment in the community for persons in need of mental health
care].
AB - BACKGROUND: Clinical admissions and inpatient services are increasingly replaced
by enhanced community treatment in Western countries. Currently the Dutch mental
health legislation is being revised, making compulsory community treatment a
novel legal option in The Netherlands. AIM: To summarize the current literature
on compulsory community treatment and to review studies relating to efficacy,
patients' and carers' perspectives, and costs. METHOD: We conducted a systematic
review of the literature, using PubMed and Trip. RESULTS: Current literature does
not provide evidence for positive effects of cct in comparison to voluntary care
in terms of admission duration, time-to-readmission, and clinical outcomes.
CONCLUSION: Results from England and the United States do not provide support for
efficacy of cct in terms of number and/or duration of hospital admissions, and in
terms of clinical outcomes compared to voluntary treatment. There is a pressing
need for studies designed to allow for direct comparisons between outcomes after
compulsory hospital admission and compulsory community treatment.
PMID- 28421575
TI - [Prescribing psychotropic medication by the nurse practitioner in mental health
care: an explorative study].
AB - BACKGROUND: Since January 1, 2012, nurse practitioners (NP) working in mental
health care are allowed to prescribe psychotropic medication. So far, there has
been very little research on the results of this decision that now let NPS share
with doctors prescribing psychotropic drugs. AIM: To provide insight into how
patients and psychiatrists experience the prescribing behaviours of NPS and how
NPS themselves regard their extended role. METHOD: We performed an explorative
study in which we used the data given in prescriptions written by NPS,
questionnaires exploring patients' experiences and semi-structured interviews
with psychiatrists and NPS. RESULTS: Between May 2014 and May 2015, 13 NPS wrote
3542 prescriptions for 565 unique patients. On the whole, patients, psychiatrists
and NPS expressed positive views on the prescribing of psychotropic medication by
NPS. CONCLUSION: Our research project confirms that the various stakeholders are
satisfied with the prescribing practices of NPS. A follow-up study is needed in
order to ascertain whether there are qualitative differences between the
prescriptions of NPS and those of doctors.
PMID- 28421576
TI - [Confusion caused by dietary supplement lithium orotate].
AB - A 38-year-old woman was referred to our hospital with pelvic inflammatory
disease. She had been diagnosed as having a tubo-ovarian abscess, for which
antibiotic therapy with metronidazole and levofloxacin was indicated. Because the
patient was already taking lithium she was prescribed clindamycin instead of
metronidazole, a drug that interacts with lithium. For the same reason, naproxen
could not be prescribed to reduce pain. However, the lithium taken by the patient
turned out to be a dietary supplement containing lithium orotate which she had
obtained via the Internet. Because the serum lithium level proved to be below
0.05 mmol/l clindamycin was still replaced by metronidazole, and naproxen could
be started.
PMID- 28421577
TI - ?
PMID- 28421578
TI - ?
PMID- 28421579
TI - ?
PMID- 28421580
TI - ?
PMID- 28421581
TI - [Are you for or against ROM?]
PMID- 28421582
TI - Polish Forum for Prevention Guidelines on Smoking: update 2017.
PMID- 28421583
TI - Heater-cooler unit contamination with Mycobacterium chimaera - potential harmful
risks for cardiac surgery patients.
PMID- 28421584
TI - Left main coronary artery quadrifurcation and acute coronary syndrome.
PMID- 28421585
TI - Left ventricular non-compaction associated with hypertrophic cardiomyopathy in
the same patient.
PMID- 28421586
TI - Cardiac approach to a patient with breast cancer and metastases in
musculoskeletal system.
PMID- 28421587
TI - Intensive exercise and its effect on the heart: Is more always better?
PMID- 28421588
TI - Takotsubo syndrome after pericardial tamponade following cryoballoon ablation of
pulmonary veins for paroxysmal atrial fibrillation and complicated by right
coronary artery thrombosis.
PMID- 28421589
TI - Spontaneous coronary dissection: Optical coherence tomography insights before and
after stenting.
PMID- 28421590
TI - Double outlet right ventricle with absent infundibular septum and common
ventriculo-arterial valve.
PMID- 28421591
TI - "Full Plastic-Jacket": Reconstruction of 18 cm of coronary arteries with
bioresorbable vascular scaffolds in a young patient with ST-elevation myocardial
infarction and multivessel disease.
PMID- 28421592
TI - Left ventricular improvement due to allogeneic CB-MNCs transplantation in a
chronic heart failure six-years after myocardial infarction.
PMID- 28421593
TI - Determinants of improvement in six-minute walk distance from admission to
discharge in acute systolic heart failure: Analysis from the ESCAPE trial.
PMID- 28421594
TI - Anti-aggregation therapy in patients with acute coronary syndrome -
recommendations for medical emergency teams. Experts' standpoint.
PMID- 28421595
TI - Acute occlusion of the superficial femoral artery in a very young woman.
PMID- 28421596
TI - The relation between skin conductance responses and recovery from symptoms of
PTSD.
AB - BACKGROUND: The purpose was to investigate if potentially stressful reminders of
the intensive care unit (ICU) stay influenced variability in transient skin
conductance responses, and whether such changes were associated with post
traumatic stress symptoms (PTSS), and development of symptoms over time. METHODS:
Thirty patients with an ICU length of stay > 48 h were included in the study.
Within the week after ICU discharge (T1), patients were exposed to authentic ICU
sound and questions regarding traumatic ICU memories while skin conductance
reactivity was monitored. PTSS was assessed using PTSS-10 at T1 and again 3
months later (T2). Changes in number of skin conductance fluctuations per second
(NSCF) between baseline and during the cueing conditions and in relation to PTSS
scores (T1) were investigated. PTSS scores at T2 and changes between T1 and T2
(PTSS-CS) were used to investigate if reactivity in NSCF could predict symptoms
of PTSD. RESULTS: The results showed increases in NSCF during both situational
and verbal cueing, compared to baseline. However, no relation to PTSS scores was
indicated. Negative correlations between NSCF during situational cueing and both
PTSS-T2 and PTSS-CS were found among women, but not among men. CONCLUSION: A low
variability, or reactivity in skin conductance responses to situational cues
could imply a risk of developing, or not being able to recover from, symptoms of
PTSD in women. As such, the measurement could be used to predict this risk in
women. However, further studies are necessary to evaluate this area of
application.
PMID- 28421597
TI - Analysis of an electrical impedance spectroscopy system in short-term digital
dermoscopy imaging of melanocytic lesions.
AB - BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic
technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of
adding an EIS measurement at baseline to suspicious melanocytic lesions
undergoing routine short-term sequential digital dermoscopy imaging (SDDI).
METHODS: Patients presented with suspicious melanocytic lesions that were
eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy).
EIS measurement was performed at the first visit following dermoscopic
photography. Normally, an EIS score of >= 4 is considered positive; however, this
protocol investigated a higher cut-off in combination with SDDI. When the EIS
score was >= 7 the lesion was excised immediately owing to the high risk of
melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3
month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign
lesions received an EIS score of 0-6, giving a specificity of the EIS method for
the diagnosis of melanoma of 83.1% [95% confidence interval (CI) 76.3-88.7]. Five
of the six melanomas found in this study had an EIS score >= 7, with a
sensitivity for melanoma diagnosis of 83.3% (95% CI 35.9-99.6). When EIS 0-6
lesions were subsequently followed up with SDDI, one additional melanoma was
detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of
100% (95% CI 54.1-100; six of six malignant melanomas excised) and a specificity
of 69.5% (95% CI 61.5-76.6; 107 of 154 benign lesions not excised). CONCLUSIONS:
If utilizing a protocol where an EIS score <= 3 requires no SDDI and >= 7
requires immediate excision, it reduced the need for SDDI by 46.9% (n = 75/160;
95% CI 39.0-54.9).
PMID- 28421598
TI - Fluorescence-advanced videodermatoscopy: a new method for in vivo skin
evaluation.
PMID- 28421599
TI - Surgery versus conservative management of endometriomas in subfertile women. A
systematic review.
AB - INTRODUCTION: Endometriomas are present in up to 44% of all women with
endometriosis and have a detrimental effect on fertility. However, it is
controversial whether endometriomas should be surgically removed before assisted
reproduction technology. Our purpose was to evaluate whether surgical stripping
of endometriomas in subfertile women improves the chance of a live birth.
Secondary outcomes were impact on ovarian reserve and pain. MATERIAL AND METHODS:
We conducted a systematic review and meta-analysis with results reported in
accordance to the PRISMA guidelines. A summary of findings table was developed
using GRADE. We searched Medline and Embase. Two reviewers performed the
screening. RESULTS: Of 686 manuscripts, we included one randomized controlled
trial and nine retrospective cohort studies, mostly of low quality. The odds
ratio for live birth after surgery [compared with conservative management before
in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)] was 0.87
(95% CI 0.64-1.18, six studies, I2 = 3%; ????, VERY LOW quality). The mean
difference of antral follicle count was -2.09 (95% CI -4.84 to 0.67, four
studies). No difference was observed regarding antral follicle count between the
two groups (MD -2.09, 95% CI -4.84 to 0.67, four studies, ????, VERY LOW
quality). Pain outcome was not reported in the included studies. CONCLUSION: The
very low quality evidence suggests no difference in odds ratio of live birth
between women who underwent surgery for endometriomas before IVF/ICSI compared
with conservative management. Further high quality studies are needed, but due to
a lack of convincing evidence favoring surgery, we recommend considering
conservative treatment if the only indication is subfertility.
PMID- 28421600
TI - Lay-led and peer support interventions for adolescents with asthma.
AB - BACKGROUND: Adolescents with asthma are at high risk of poor adherence with
treatment. This may be compounded by activities that worsen asthma, in particular
smoking. Additional support above and beyond routine care has the potential to
encourage good self-management. We wanted to find out whether sessions led by
their peers or by lay leaders help to reduce these risks and improve asthma
outcomes among adolescents. OBJECTIVES: To assess the safety and efficacy of lay
led and peer support interventions for adolescents with asthma. SEARCH METHODS:
We identified trials from the Cochrane Airways Trials Register, which contains
reports of randomised trials obtained from multiple electronic and handsearched
sources, and we searched trial registries and reference lists of primary studies.
We conducted the most recent searches on 25 November 2016. SELECTION CRITERIA:
Eligible studies randomised adolescents with asthma to an intervention led by lay
people or peers or to a control. We included parallel randomised controlled
trials with individual or cluster designs. We included studies reported as full
text, those published as abstract only and unpublished data. DATA COLLECTION AND
ANALYSIS: Two review authors screened the searches, extracted numerical data and
study characteristics and assessed each included study for risk of bias. Primary
outcomes were asthma-related quality of life and exacerbations requiring at least
a course of oral steroids. We graded the analyses and presented evidence in a
'Summary of findings' table.We analysed dichotomous data as odds ratios, and
continuous data as mean differences (MD) or standardised mean differences, all
with a random-effects model. We assessed clinical, methodological and statistical
heterogeneity when performing meta-analyses, and we described skewed data
narratively. MAIN RESULTS: Five studies including a total of 1146 participants
met the inclusion criteria for this review. As ever with systematic reviews of
complex interventions, studies varied by design (cluster and individually
randomised), duration (2.5 to 9 months), setting (school, day camp, primary care)
and intervention content. Most risk of bias concerns were related to blinding and
incomplete reporting, which limited the meta-analyses that could be performed.
Studies generally controlled well for selection and attrition biases.All
participants were between 11 and 17 years of age. Asthma diagnosis and severity
varied, as did smoking prevalence. Three studies used the Triple A programme; one
of these studies tested the addition of a smoke-free pledge; another delivered
peer support group sessions and mp3 messaging to encourage adherence; and the
third compared a peer-led asthma day camp with an equivalent camp led by
healthcare practitioners.We had low confidence in all findings owing to risk of
bias, inconsistency and imprecision. Results from an analysis of asthma-related
quality of life based on the prespecified random-effects model were imprecise and
showed no differences (MD 0.40, 95% confidence interval (CI) -0.02 to 0.81); a
sensitivity analysis based on a fixed-effect model and a responder analysis
suggested small benefit may be derived for this outcome. Most other results were
summarised narratively and did not show an important benefit of the intervention;
studies provided no analysable data on asthma exacerbations or unscheduled visits
(data were skewed), and one study measuring adherence reported a drop in both
groups. Effects on asthma control favoured the intervention but findings were not
statistically significant. Results from two studies with high levels of baseline
smoking showed some promise for self-efficacy to stop smoking, but overall
nicotine dependence and smoking-related knowledge were not significantly better
in the intervention group. Investigators did not report adverse events. AUTHORS'
CONCLUSIONS: Although weak evidence suggests that lay-led and peer support
interventions could lead to a small improvement in asthma-related quality of life
for adolescents, benefits for asthma control, exacerbations and medication
adherence remain unproven. Current evidence is insufficient to reveal whether
routine use of lay-led or peer support programmes is beneficial for adolescents
receiving asthma care.Ongoing and future research may help to identify target
populations for lay-led and peer support interventions, along with attributes
that constitute a successful programme.
PMID- 28421602
TI - The qualitative f-ratio method applied to electron channelling-induced x-ray
imaging with an annular silicon drift detector in a scanning electron microscope
in the transmission mode.
AB - Electron channelling is known to affect the x-ray production when an accelerated
electron beam is applied to a crystalline material and is highly dependent on the
local crystal orientation. This effect, unless very long counting time are used,
is barely noticeable on x-ray energy spectra recorded with conventional silicon
drift detectors (SDD) located at a small elevation angle. However, the very high
count rates provided by the new commercially available annular SDDs permit now to
observe this effect routinely and may, in some circumstances, hide the true
elemental x-ray variations due to the local true specimen composition. To
circumvent this issue, the recently developed f-ratio method was applied to
display qualitatively the true net intensity x-ray variations in a thin specimen
of a Ti-6Al-4V alloy in a scanning electron microscope in transmission mode. The
diffraction contrast observed in the x-ray images was successfully cancelled
through the use of f-ratios and the true composition variations at the grain
boundaries could be observed in relation to the dislocation alignment prior to
the beta-phase nucleation. The qualitative effectiveness in removing channelling
effects demonstrated in this work makes the f-ratio, in its quantitative form, a
possible alternative to the ZAF method in channelling conditions.
PMID- 28421601
TI - Evaluation of the reliability of the Cutaneous Dermatomyositis Disease Area and
Severity Index and the Cutaneous Assessment Tool-Binary Method in juvenile
dermatomyositis among paediatric dermatologists, rheumatologists and
neurologists.
AB - BACKGROUND: The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)
and Cutaneous Assessment Tool-Binary Method (CAT-BM) have been shown to be
reliable and valid outcome measures to assess cutaneous disease in adult
dermatomyositis (DM) and juvenile DM (JDM), respectively. OBJECTIVES: This study
compared the CDASI and CAT-BM for use by paediatric dermatologists, paediatric
rheumatologists and paediatric neurologists in patients with JDM. METHODS: Five
paediatric dermatologists, five paediatric rheumatologists and five paediatric
neurologists each evaluated 14 patients with JDM using the CDASI, CAT-BM, and
skin Physician Global Assessment (PGA) scales. Inter-rater reliability, intra
rater reliability, construct validity and completion time were compared. RESULTS:
Inter-rater reliability for CDASI activity and damage scores was good to moderate
for paediatric dermatologists and rheumatologists, but poor for paediatric
neurologists. The inter-rater reliability for CAT-BM activity scores was moderate
for paediatric dermatologists and rheumatologists, but poor for paediatric
neurologists and poor across all specialties for damage scores. Intra-rater
reliability for the CDASI and CAT-BM activity and damage scores was moderate to
excellent for paediatric dermatologists, rheumatologists and neurologists. Strong
associations were found between skin PGA activity and damage scores and CDASI or
CAT-BM activity and damage scores, respectively (P < 0.002). The CDASI had a mean
completion time of 5.4 min compared with that for the CAT-BM of 3.1 min.
CONCLUSIONS: Our data confirm the reliability of the CDASI activity and damage
scores and the CAT-BM activity scores when used by paediatric dermatologists and
rheumatologists in assessing JDM. Significant variation existed in the paediatric
neurologists' scores.
PMID- 28421603
TI - High payload itraconazole-incorporated lipid nanoparticles with modulated release
property for oral and parenteral administration.
AB - OBJECTIVES: The aim of this study was to develop high payload itraconazole
incorporated lipid nanoparticles (HINP) with modulated release property using a
binary mixture core of solid and liquid lipid for oral and parenteral
administration. METHODS: High payload itraconazole-incorporated lipid
nanoparticles were prepared by hot high-pressure homogenization method using
tristearin (TS) as a solid lipid, triolein (TO) as a liquid lipid and egg
phosphatidylcholine/Tween 80/DSPE-PEG2000 as a surfactants mixture. To
investigate the effects of liquid lipid in lipid core on itraconazole (ITZ)
dissolution and release, TS/TO ratio was varied as 100/0, 90/10 and 80/20
(mg/mg). KEY FINDINGS: All HINP formulations showed particle size around 300 nm
and polydispersity index below 0.3. The incorporation efficiencies of HINP
formulations were above 80%, and more than 40 mg of ITZ was incorporated into
each HINP formulation. In-vitro dissolution and release rate of ITZ from HINP
increased as the amount of TO in lipid core increased. Compared with commercial
formulations of ITZ, the pharmacokinetics of ITZ was improved after oral and
parenteral administration of HINP formulations containing 0% or 10% of TO in
lipid core. CONCLUSION: High payload itraconazole-incorporated lipid
nanoparticles with a binary mixture lipid core have a great potential for the
development of controlled release formulation of ITZ.
PMID- 28421604
TI - Comparison of adverse pregnancy outcomes based on the new IADPSG 2010 gestational
diabetes criteria and maternal body mass index.
AB - BACKGROUND: The diagnostic criteria for gestational diabetes (GDM) have been
controversial following the International Association for Pregnancy Study Groups
(IADPSG) 2010 recommendations to lower the diagnostic fasting blood sugar level
threshold. AIM: To assess the pregnancy-related outcomes of women according to
the different diagnostic criteria for GDM adjusting for body mass index
categories. METHOD: A retrospective observational cohort study was conducted on
4081 pregnant women with positive 50 g glucose challenge test but without pre
gestational diabetes. Participants were grouped into four cohorts: no GDM
(control group); GDM on Australasian Diabetes in Pregnancy (ADIPS) 1998 criteria
only (treated); GDM on IADPSG 2010 criteria only (untreated); and GDM on both
criteria (treated). The association of each cohort with pregnancy outcome
measures, including birthweight centile, delivery gestation, primary caesarean
section, shoulder dystocia and stillbirth, together with the effect of obesity,
were examined. RESULTS: Women diagnosed with GDM according to the IADPSG 2010
(untreated) but not the ADIPS 1998 criteria (treated) had an increased risk of
being large for gestational age (LGA) (odds ratio (OR) = 2.45, 95% CI: 1.46-4.12,
P = 0.001) and primary caesarean section (OR = 2.03, 95% CI: 1.23-3.35, P =
0.006) compared to control women. Among the women in this untreated group and
women without GDM, obese women had an increased risk of LGA (OR = 3.82, 95% CI:
2.87-5.10, P < 0.001), shoulder dystocia (OR = 1.50, 95% CI: 1.03-2.19, P = 0.04)
and primary caesarean section (OR = 1.63, 95% CI: 1.26-2.10, P < 0.001), compared
to those women of normal weight. These associations remained significant on
multivariate analysis. CONCLUSION: Untreated women who would be diagnosed with
GDM using the new criteria have an increased risk of pregnancy complications,
with maternal obesity having an even greater risk.
PMID- 28421605
TI - Cholinergic/glutamatergic co-transmission in striatal cholinergic interneurons:
new mechanisms regulating striatal computation.
AB - It is well established that neurons secrete neuropeptides and ATP with classical
neurotransmitters; however, certain neuronal populations are also capable of
releasing two classical neurotransmitters by a process named co-transmission.
Although there has been progress in our understanding of the molecular mechanism
underlying co-transmission, the individual regulation of neurotransmitter
secretion and the functional significance of this neuronal 'bilingualism' is
still unknown. Striatal cholinergic interneurons (CINs) have been shown to
secrete glutamate (Glu) in addition to acetylcholine (ACh) and are recognized for
their role in the regulation of striatal circuits and behavior. Our review
highlights the recent research into identifying mechanisms that regulate the
secretion and function of Glu and ACh released by CINs and the roles these
neurons play in regulating dopamine secretion and striatal activity. In
particular, we focus on how the transporters for ACh (VAChT) and Glu (VGLUT3)
influence the storage of neurotransmitters in CINs. We further discuss how these
individual neurotransmitters regulate striatal computation and distinct aspects
of behavior that are regulated by the striatum. We suggest that understanding the
distinct and complementary functional roles of these two neurotransmitters may
prove beneficial in the development of therapies for Parkinson's disease and
addiction. Overall, understanding how Glu and ACh secreted by CINs impacts
striatal activity may provide insight into how different populations of
'bilingual' neurons are able to develop sophisticated regulation of their targets
by interacting with multiple receptors but also by regulating each other's
vesicular storage. This is an article for the special issue XVth International
Symposium on Cholinergic Mechanisms.
PMID- 28421607
TI - Laterality and grip strength influence hand bone micro-architecture in modern
humans, an HRpQCT study.
AB - It is widely hypothesized that mechanical loading, specifically repetitive low
intensity tasks, influences the inner structure of cancellous bone. As such,
there is likely a relationship between handedness and bone morphology. The aim of
this study is to determine patterns in trabecular bone between dominant and non
dominant hands in modern humans. Seventeen healthy patients between 22 and 32
years old were included in the study. Radial carpal bones (lunate, capitate,
scaphoid, trapezium, trapezoid, 1st, 2nd and 3rd metacarpals) were analyzed with
high-resolution micro-computed tomography. Additionally, crush and pinch grip
were recorded. Factorial analysis indicated that bone volume ratio, trabeculae
number (Tb.N), bone surface to volume ratio (BS.BV), body weight, stature and
crush grip were all positively correlated with principal components 1 and 2
explaining 78.7% of the variance. Volumetric and trabecular endostructural
parameters (BV/TV, BS/BV or Tb.Th, Tb.N) explain the observed inter-individual
variability better than anthropometric or clinical parameters. Factors analysis
regressions showed correlations between these parameters and the dominant side
for crush strength for the lunate (r2 = 0.640, P < 0.0001), trapezium (r2 =
0.836, P < 0.0001) and third metacarpal (r2 = 0.763). However, despite a
significant lateralization in grip strength for all patients, the endostructural
variability between dominant and non-dominant sides was limited in perspective to
inter-individual differences. In conclusion, handedness is unlikely to generate
trabecular patterns of asymmetry. It appears, however, that crush strength can be
considered for endostructural analysis in the modern human wrist.
PMID- 28421606
TI - Role of mucosa in generating spontaneous activity in the guinea pig seminal
vesicle.
AB - KEY POINTS: The mucosa may have neuron-like functions as urinary bladder mucosa
releases bioactive substances that modulate sensory nerve activity as well as
detrusor muscle contractility. However, such mucosal function in other visceral
organs remains to be established. The role of mucosa in generating spontaneous
contractions in seminal vesicles (SVs), a paired organ in the male reproductive
tract, was investigated. The intact mucosa is essential for the generation of
spontaneous phasic contractions of SV smooth muscle arising from electrical slow
waves and corresponding increases in intracellular Ca2+ . These spontaneous
events primarily depend on Ca2+ handling by sarco-endoplasmic reticulum Ca2+
stores. A population of mucosal cells developed spontaneous rises in
intracellular Ca2+ relying on sarco-endoplasmic reticulum Ca2+ handling. The
spontaneously active cells in the SV mucosa appear to drive spontaneous activity
in smooth muscle either by sending depolarizing signals and/or by releasing
humoral substances. ABSTRACT: The role of the mucosa in generating the
spontaneous activity of guinea-pig seminal vesicle (SV) was explored. Changes in
contractility, membrane potential and intracellular Ca2+ dynamics of SV smooth
muscle cells (SMCs) were recorded using isometric tension recording,
intracellular microelectrode recording and epi-fluorescence Ca2+ imaging,
respectively. Mucosa-intact but not mucosa-denuded SV preparations generated TTX-
(1 MUm) resistant spontaneous phasic contractions that were abolished by
nifedipine (3 MUm). Consistently, SMCs developed mucosa-dependent slow waves
(SWs) that triggered action potentials and corresponding Ca2+ flashes. Nifedipine
(10 MUm) abolished the action potentials and spontaneous contractions, while
suppressing the SWs and Ca2+ flashes. Both the residual SWs and spontaneous Ca2+
transients were abolished by cyclopiazonic acid (CPA, 10 MUm), a sarco
endoplasmic reticulum Ca2+ -ATPase (SERCA) inhibitor. DIDS (300 MUm) and niflumic
acid (100 MUm), blockers for Ca2+ -activated Cl- channels (CACCs), or low Cl-
solution also slowed or prevented the generation of SWs. In SV mucosal
preparations detached from the muscle layer, a population of mucosal cells
generated spontaneous Ca2+ transients that were blocked by CPA but not
nifedipine. These results suggested that spontaneous contractions and
corresponding Ca2+ flashes in SV SMCs arise from action potential generation due
to the opening of L-type voltage-dependent Ca2+ channels. Spontaneous Ca2+
transients appear to primarily result from Ca2+ release from sarco-endoplasmic
reticulum Ca2+ stores to activate CACCs to develop SWs. The mucosal cells firing
spontaneous Ca2+ transients may play a critical role in driving spontaneous
activity of SV smooth muscle either by sending depolarizing signals or by
releasing humoral substances.
PMID- 28421608
TI - Can functional emotion regulation protect children's mental health from war
trauma? A Palestinian study.
AB - Effective emotion regulation (ER) is expected to protect mental health in
traumatic stress. We first analysed the protective (moderator) function of
different ER strategies and the associations between ER and mental health.
Second, we tested gender differences in the protective function of ER and the
associations between ER strategies and mental health. Participants were 482
Palestinian children (girls 49.4%; 10-13 years, M = 11.29, SD = .68) whose ER was
assessed by the Emotion Regulation Questionnaire and mental health by post
traumatic stress (Children's Impact Event Scale), depressive, and psychological
distress (Strengths and Difficulties Questionnaire) symptoms, and by psychosocial
well-being (Mental Health Continuum-Short Form). War trauma involved 42 events.
Results showed, first, that none of the ER strategies could protect a child's
mental health from negative impact of war trauma, but self-focused ER was
associated with low depressive symptoms, and other-facilitated ER with high
psychological well-being. However, controlling of emotions formed a comprehensive
risk for children's mental health. Second, gender differences were found in the
protective role of ER, as self-focused and distractive ER formed a vulnerability
among boys. The results are discussed in the context of emotional and regulative
demands of war and life-threat.
PMID- 28421609
TI - Description and quantitative analysis of the dentition of the southern thorny
skate Amblyraja doellojuradoi.
AB - A description of the tooth morphology of 234 jaws from the southern thorny skate
Amblyraja doellojuradoi in the south-west Atlantic Ocean is given. Seven rows of
teeth were selected and length and width of each tooth in these rows were
measured. It was found that functional series corresponds to the third teeth and
the average width and length of these teeth were compared among jaws, maturity
stages, sexes and rows. Generalized linear models were used to determine the
subset of measures that most contribute to explain the variability between
groups. It was observed that males have longer teeth than females, but the teeth
of females are wider. These differences are attributed to reproductive behaviour,
in which males bite females to hold them during copulation. This study provides a
description of the teeth of A. doellojuradoi, supplying a valuable tool for
identification of species. In addition, the establishment of the main variations
observed in the dentition, improves the understanding of the species' biology.
PMID- 28421610
TI - Use of vegetable oils in dermatology: an overview.
AB - Vegetable oils have been used for a wide variety of purposes since time
immemorial; however, their principle use remains as skin moisturizers, especially
in neonates and children. Because of their considerable efficacy and a low side
effect profile and bearable cost, these oils are hugely popular as moisturizers
among the common people in countries such as India. A wide variety of oils have
been used, and newer ones are coming up with each passing day. This article
focuses on the different types of vegetable oils and their varied uses in
dermatology.
PMID- 28421611
TI - Breast-density measurement using photon-counting spectral mammography.
AB - PURPOSE: To evaluate a method for measuring breast density using photon-counting
spectral mammography. Breast density is an indicator of breast cancer risk and
diagnostic accuracy in mammography, and can be used as input to personalized
screening, treatment monitoring and dose estimation. METHODS: The measurement
method employs the spectral difference in x-ray attenuation between adipose and
fibro-glandular tissue, and does not rely on any a priori information. The method
was evaluated using phantom measurements on tissue-equivalent material (slabs and
breast-shaped phantoms) and using clinical data from a screening population
(n=1329). A state-of-the-art nonspectral method for breast-density assessment was
used for benchmarking. RESULTS: The precision of the spectral method was
estimated to be 1.5-1.8 percentage points (pp) breast density. Expected
correlations were observed in the screening population for thickness versus
breast density, dense volume, breast volume, and compression height. Densities
ranged between 4.5% and 99.6%, and exhibited a skewed distribution with a mode of
12.5%, a median of 18.3%, and a mean of 23.7%. The precision of the nonspectral
method was estimated to be 2.7-2.8 pp. The major uncertainty of the nonspectral
method originated from the thickness estimate, and in particular thin/dense
breasts posed problems compared to the spectral method. CONCLUSIONS: The spectral
method yielded reasonable results in a screening population with a precision
approximately two times that of the nonspectral method, which may improve or
enable applications of breast-density measurement on an individual basis such as
treatment monitoring and personalized screening.
PMID- 28421612
TI - Prospective bacterial quorum sensing inhibitors from Indian medicinal plant
extracts.
AB - : As virulence of many pathogenic bacteria is regulated by the phenomenon of
quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I)
property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in
the leaf extract was evaluated by its ability to inhibit production of pigment in
Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC
2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three
plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown
a dose-dependent inhibition of violacein production with no negative effect on
bacterial growth. Inhibition of pyocyanin pigment production and swarming
motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained
by gas chromatography-mass spectroscopy (GC-MS) and thin-layer chromatography
direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid
compounds found in the three plant extracts could have QS-I activity.
SIGNIFICANCE AND IMPACT OF THE STUDY: A novel alternative prospect to prevent
bacterial infections without inhibiting the growth is to apply chemicals that
inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61
medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit
production of pigment (violacein in Chromobacterium violaceum MTCC 2656,
pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC
2297. The most prospective plants (for the development of quorum sensing
inhibitor), showing inhibition of violacein production without affecting
bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia
nepalensis.
PMID- 28421613
TI - Intoxication-Related Alcohol Mixed with Energy Drink Expectancies Scale: Initial
Development and Validation.
AB - BACKGROUND: Young adult use of alcohol mixed with energy drinks (AmEDs) has been
linked with elevated risks of a constellation of problem behaviors. These risks
may be conditioned by expectancies regarding the effects of caffeine in
conjunction with alcohol consumption. The aim of this study was to describe the
construction and psychometric evaluation of the Intoxication-Related AmED
Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how
the experience of AmED intoxication differs from the experience of noncaffeinated
alcohol (NCA) intoxication. METHODS: Scale development and testing were conducted
using data from a U.S. national sample of 3,105 adolescents and emerging adults
aged 13 to 25. Exploratory and confirmatory factor analyses were conducted to
evaluate the factor structure and establish factor invariance across gender, age,
and prior experience with AmED use. Cross-sectional and longitudinal analyses
examining correlates of AmED use were used to assess construct and predictive
validity. RESULTS: In confirmatory factor analyses, fit indices for the
hypothesized 4-factor structure (i.e., Intoxication Management [IM], Alertness
[AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the
data. Together, these factors accounted for 75.3% of total variance. The factor
structure was stable across male/female, teen/young adult, and AmED experience/no
experience subgroups. The resultant unit-weighted subscales showed strong
internal consistency and satisfactory convergent validity. Baseline scores on the
IM, SO, and JT subscales predicted changes in AmED use over a subsequent 3-month
period. CONCLUSIONS: The AmED_EXPI appears to be a reliable and valid tool for
measuring expectancies about the effects of caffeine during alcohol intoxication.
PMID- 28421614
TI - A first look at the effects of long inter-pregnancy interval and advanced
maternal age on perinatal outcomes: A retrospective cohort study.
AB - BACKGROUND: After China's One-child Policy was replaced with the Two-child Policy
in 2013, the rate of second pregnancies with a longer inter-pregnancy interval
(IPI) has suddenly increased in that country; however, the effect of long IPIs
(>=49 months) on perinatal outcomes remains unreported. METHODS: This was a
retrospective cohort study in China from July 2015 through June 2016. We used
univariate and multivariate logistic regression models to test the associations
among IPI, maternal age, and perinatal outcome (preterm delivery, term low
birthweight, and small-for-gestational age). We included baseline factors and
variables with biological plausibility as confounders. RESULTS: Our analytic
sample included 3309 second pregnancies. The mean IPI was 75.36 months. Compared
with second pregnancies with a short IPI of 7-24 months, those with long IPIs had
higher adjusted odds ratios (ORs) of preterm delivery (1.70-2.00 [95% CI 1.20
3.33]) and term low birthweight (2.16-2.68 [1.10-6.17]), but not small-for
gestational age. The mean maternal age at current delivery was 32.0 years.
Compared with the reference group (25-29 years), second pregnancies for the
oldest maternal age group (>=35 years) showed no statistically significant
increased ORs for adverse perinatal outcomes. CONCLUSION: Long IPI is a
significant contributor to preterm delivery and term low birthweight. Health care
providers need to pay close attention to preterm delivery prevention and fetal
growth during prenatal care for second pregnancies where the mothers have long
IPIs.
PMID- 28421615
TI - The effects of oat beta-glucan incorporation on the quality, structure, consumer
acceptance and glycaemic response of steamed bread.
AB - : The objective of this study was to evaluate the effects of the incorporation of
oat beta-glucan (ObetaG) on the sensory and nutritional quality of steamed bread.
Wheat flour was substituted with ObetaG at levels varying from 0 g/100 g to 5
g/100 g. The results showed that the products containing 1 g/100 g and 3 g/100 g
ObetaG produced a comparable overall consumer acceptance while a significantly
lower score was given to the product with 5 g/100 g. Nutritionally, the presence
of ObetaG impeded in vitro starch hydrolysis by amylolytic enzymes. More
importantly, the addition of ObetaG up to 5 g/100 g did bring about a lower in
vitro predicted glycaemic index to steamed bread, but it generated insignificant
effects on the in vivo glycaemic response. The current work first demonstrated
the feasibility of fabricating ObetaG-enriched steamed bread and its nutritional
superiority compared to the corresponding normal product. PRACTICAL APPLICATIONS:
Modern methods of food elaboration and processing frequently reduce the content
of dietary fiber (DF). Despite the well-known health benefits of DF consumption,
average intake levels still fall far below recommended ones. Oat beta-glucan
(ObetaG) is a kind of indigestible polysaccharide with diverse bioactivity. This
article evaluated the effects of ObetaG incorporation on quality, structure,
consumer acceptance, and glycaemic response of steamed bread. The addition of
less than 3 g/100 g of ObetaG had negligible effects on the consumer acceptance
of steamed bread. The enrichment at 5 g/100 g indeed deteriorated the consumer
acceptance. Moreover, ObetaG highly lowered the glycaemic response of steamed
bread. The current work first demonstrated the feasibility of fabricating ObetaG
enriched steamed bread and its nutritional superiority compared to the
corresponding normal product. ObetaG enriched steamed bread may offer an
alternative to improve DF intake of residents.
PMID- 28421616
TI - The Validity of the Montgomery-Asberg Depression Rating Scale in an Inpatient
Sample with Alcohol Dependence.
AB - BACKGROUND: The Montgomery-Asberg Depression Rating Scale (MADRS) is commonly
used to examine depressive symptoms in clinical settings, including facilities
treating patients for alcohol addiction. No studies have examined the validity of
the MADRS compared to an established clinical diagnostic tool of depression in
this population. This study aimed to examine the following: (i) the validity of
the MADRS compared to a clinical diagnosis of a depressive disorder (using the
Structured Clinical Interview for DSM-IV-TR [SCID-IV-TR]) in patients seeking
treatment for alcohol dependence (AD); (ii) whether the validity of the MADRS
differs by type of SCID-IV-TR-based diagnosis of depression; and (iii) which
items contribute to the optimal predictive model of the MADRS compared to a SCID
IV-TR diagnosis of a depressive disorder. METHODS: Individuals seeking treatment
for AD and admitted to an inpatient unit were administered the MADRS at day 2 of
their detoxification program. Clinical diagnoses of AD and depression were made
via the SCID-IV-TR at the beginning of treatment. RESULTS: In total, 803
participants were included in the study. The MADRS demonstrated low overall
accuracy relative to the clinical diagnosis of depression with an area under the
receiver operating characteristic curve of 0.68. The optimal threshold for
balancing sensitivity and specificity identified by the Euclidean distance was
>14. This cut-point demonstrated a sensitivity of 66%, a specificity of 60%, a
positive predictive value of 50%, and a negative predictive value of 75%. The
MADRS performed slightly better for major depressive disorders compared to
alcohol-induced depression. Items related to lassitude, concentration, and
appetite slightly decreased the accuracy of the MADRS. CONCLUSIONS: The MADRS
does not appear to be an appropriate substitute for a diagnostic tool among
alcohol-dependent patients. The MADRS may, however, still be a useful screening
tool assuming careful consideration of cut-points.
PMID- 28421618
TI - Diffusiophoresis of a charged particle in a microtube.
AB - The diffusiophoresis of a charged sphere along the axis of a circular microtube
filled with an electrolyte solution is studied theoretically. The tube wall may
be either nonconductive and impermeable or prescribed with a linear electrolyte
concentration distribution. The electric double layers at the solid surfaces are
thin, but the diffuse-layer polarization effect over the particle surface is
considered. The general solutions to the electrokinetic differential equations
are expressed in spherical and cylindrical coordinates, whereas the boundary
conditions at the particle surface are satisfied by a collocation technique. The
collocation solutions for the diffusiophoretic velocity of the particle, which
are in good agreement with the asymptotic formula derived from a reflection
method, are obtained for various values of the radius ratio and zeta potential
ratio between the particle and the microtube and of other relevant parameters.
The contributions from the diffusioosmotic flow along the tube wall and wall
corrected diffusiophoretic driving force to the particle velocity can be
superimposed due to the linearity. Although the diffusiophoretic velocity in an
uncharged microtube is in general a decreasing function of the particle-to-tube
radius ratio and can reverse its direction, it can increase with increases in
this ratio due to the competition of the wall effects of possible electrochemical
enhancement and hydrodynamic retardation to the particle motion. When the zeta
potentials associated with the tube and particle are equivalent, the
diffusioosmotic flow induced by the tube wall dominates the diffusiophoretic
motion.
PMID- 28421617
TI - Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol
and Marijuana Use in Adolescence: Initial Findings from the National Consortium
on Alcohol and Neurodevelopment in Adolescence Study.
AB - BACKGROUND: Abundant cross-sectional evidence links eveningness (a preference for
later sleep-wake timing) and increased alcohol and drug use among adolescents and
young adults. However, longitudinal studies are needed to examine whether
eveningness is a risk factor for subsequent alcohol and drug use, particularly
during adolescence, which is marked by parallel peaks in eveningness and risk for
the onset of alcohol use disorders. This study examined whether eveningness and
other sleep characteristics were associated with concurrent or subsequent
substance involvement in a longitudinal study of adolescents. METHODS:
Participants were 729 adolescents (368 females; age 12 to 21 years) in the
National Consortium on Alcohol and Neurodevelopment in Adolescence study.
Associations between the sleep variables (circadian preference, sleep quality,
daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance
variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use
[y/n]) were examined using ordinal and logistic regression with baseline age,
sex, race, ethnicity, socioeconomic status, and psychiatric problems as
covariates. RESULTS: At baseline, greater eveningness was associated with greater
at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later
weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed
similar associations across the 3 substance outcomes at baseline. Greater
baseline eveningness was also prospectively associated with greater bingeing and
past-year use of marijuana at the 1-year follow-up, after covarying for baseline
bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and
shorter baseline weekday sleep duration, were similarly associated with greater
bingeing and past-year use of marijuana at the 1-year follow-up after covarying
for baseline values. CONCLUSIONS: Findings suggest that eveningness and sleep
timing may be under recognized risk factors and future areas of intervention for
adolescent involvement in alcohol and marijuana that should be considered along
with other previously identified sleep factors such as insomnia and insufficient
sleep.
PMID- 28421619
TI - Molecular detection of Chlamydia trachomatis and semen quality of sexual partners
of infertile women.
AB - Chlamydia trachomatis is considered as the bacterium that is more sexually
transmitted as cause of male urethritis, epididymitis, orchitis and infertility.
A total of 116 semen samples of men whose couples are infertile women were
analysed. The quality of the semen was measured by standard procedures
recommended by WHO while C. trachomatis was detected by the PCR assay. Thirty
seven semen samples were positive for C. trachomatis (31.9%). Regarding semen
analysis, no different values were observed between positive and negative samples
to C. trachomatis. However, the presence of leucocytes and erythrocytes suggests
an inflammatory process; however, these were high in negative samples to C.
trachomatis. Furthermore, an association between low seminal volume at 1, 5 ml
and the positivity to C. trachomatis was observed (OR=2, 1; CI95 % 1,16-3,07).
The total semen volume is a contribution by the various accessory glands (this
reflects the secretory activity of the glands); a low semen volume could be due
to an obstruction of the ejaculatory duct or infection of accessory glands by C.
trachomatis. More studies are necessary to identify the causes of a reduced semen
volume.
PMID- 28421620
TI - By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state
neural activity.
AB - Although the 40 Hz auditory steady-state response (ASSR) is of clinical interest,
the construct validity of EEG and MEG measures of 40 Hz ASSR cortical
microcircuits is unclear. This study evaluated several MEG and EEG metrics by
leveraging findings of (a) an association between the 40 Hz ASSR and age in the
left but not right hemisphere, and (b) right- > left-hemisphere differences in
the strength of the 40 Hz ASSR. The contention is that, if an analysis method
does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere
differences, then the obtained measures likely have low validity. Fifty-three
adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were
collected. ASSR activity was examined as a function of phase similarity
(intertrial coherence) and percent change from baseline (total power). A variety
of head models (spherical and realistic) and a variety of dipole source modeling
strategies (dipole source localization and dipoles fixed to Heschl's gyri) were
compared. Several sensor analysis strategies were also tested. EEG sensor
measures failed to detect left 40 Hz ASSR and age associations or hemisphere
differences. A comparison of MEG and EEG head-source models showed similarity in
the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations,
indicating good construct validity across models. Given a goal of measuring the
40 Hz ASSR cortical microcircuits, a source-modeling approach was shown to be
superior in measuring this construct versus methods that rely on EEG sensor
measures.
PMID- 28421621
TI - Presence of Ganglia and Telocytes in Proximity to Myocardial Sleeve Tissue in the
Porcine Pulmonary Veins Wall.
AB - Ganglia and telocytes were identified inside the porcine pulmonary veins wall
near myocardial sleeve tissue at the atriopulmonary junction. These structures
are reported to play a role in the initiation of pulses from outside the heart,
which potentially can cause cardiac conduction disorders such as atrial
fibrillation. In-depth knowledge on the fine structure of the pulmonary vein wall
is a pre-requisite to better understand the underlying pathophysiology of atrial
fibrillation and the origin and conduction of ectopic pulses. The importance of
pulmonary vein myocardial sleeves as triggering foci for atrial fibrillation has
been shown in human patients. In this context, the fine structure of the
pulmonary vein wall was investigated qualitatively by light and transmission
electron microscopy in the pig, which is a frequently used animal model for
development of new treatment strategies. Additionally, intra and extramural
ganglia, containing telocytes that create a network near the neurone cell bodies,
were identified in pigs. Detailed illustration of the distribution and
organization of tissues and cell types, potentially involved in the origin and
propagation of ectopic stimuli originating from the pulmonary veins, might lead
to a better insight on the actual composition of the tissues affected by ablation
as studied in pigs.
PMID- 28421622
TI - Bayesian inference on mixed-effects location scale models with skew-t
distribution and mismeasured covariates for longitudinal data.
AB - In AIDS studies, heterogeneous between and within subject variations are often
observed on longitudinal endpoints. To accommodate heteroscedasticity in the
longitudinal data, statistical methods have been developed to model the mean and
variance jointly. Most of these methods assume (conditional) normal distributions
for random errors, which is not realistic in practice. In this article, we
propose a Bayesian mixed-effects location scale model with skew-t distribution
and mismeasured covariates for heterogeneous longitudinal data with skewness. The
proposed model captures the between-subject and within-subject (WS) heterogeneity
by modeling the between-subject and WS variations with covariates as well as a
random effect at subject level in the WS variance. Further, the proposed model
also takes into account the covariate measurement errors, and commonly assumed
normal distributions for model errors are substituted by skew-t distribution to
account for skewness. Parameter estimation is carried out in a Bayesian
framework. The proposed method is illustrated with a Multicenter AIDS Cohort
Study. Simulation studies are performed to assess the performance of the proposed
method. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421623
TI - A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine
Transmission as Assessed by [11 C]-(+)-PHNO.
AB - BACKGROUND: Previous positron emission tomography (PET) studies exploring the
effect of acute alcohol on dopamine (DA) levels have yielded inconsistent
results, with only some studies suggesting increased synaptic DA levels after an
alcohol challenge. The D2 /D3 agonist radiotracer, [11 C]-(+)-propyl-hexahydro
naphtho-oxazin ([11 C]-(+)-PHNO), has greater sensitivity to synaptic DA
fluctuation than previously used antagonist radiotracers and is in principle more
suitable for imaging alcohol-induced changes in DA. Its high affinity for the D3
receptor also enables measuring changes in D3 -rich brain areas which have
previously been unexplored. The aim of this study was to investigate whether
alcohol reduces [11 C]-(+)-PHNO binding in the striatum and in D3 -rich extra
striatal areas. METHODS: Eight healthy drinkers underwent 2 [11 C]-(+)-PHNO PET
scans following alcohol and placebo in a randomized, single-blind, crossover
design. [11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions
were compared between the 2 scans. RESULTS: Acute alcohol administration did not
significantly reduce [11 C]-(+)-PHNO binding in either the limbic striatum (d =
0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15).
Similarly, there were no changes in binding in the D3 -rich areas of the ventral
pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15).
However, greater percent change in [11 C]-(+)-PHNO binding (DeltaBPND ) between
scans was related to lower blood alcohol levels. CONCLUSIONS: Using the agonist
radiotracer, [11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is
not associated with robust changes in tracer binding in striatal or extra
striatal regions. However, we found that changes in [11 C]-(+)-PHNO binding
following alcohol are dependent on blood alcohol levels suggesting that increases
in DA may occur at lower stimulating doses. The effect of lower doses of alcohol
on DA warrants further investigation in a larger study.
PMID- 28421624
TI - Bayesian exponential random graph modelling of interhospital patient referral
networks.
AB - Using original data that we have collected on referral relations between 110
hospitals serving a large regional community, we show how recently derived
Bayesian exponential random graph models may be adopted to illuminate core
empirical issues in research on relational coordination among healthcare
organisations. We show how a rigorous Bayesian computation approach supports a
fully probabilistic analytical framework that alleviates well-known problems in
the estimation of model parameters of exponential random graph models. We also
show how the main structural features of interhospital patient referral networks
that prior studies have described can be reproduced with accuracy by specifying
the system of local dependencies that produce - but at the same time are induced
by - decentralised collaborative arrangements between hospitals. Copyright (c)
2017 John Wiley & Sons, Ltd.
PMID- 28421626
TI - Editorial Comment from Dr Teishima and Dr Matsubara to Clinical application of
calculated split renal volume using computed tomography-based renal volumetry
after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic
acid renal scan data.
PMID- 28421625
TI - Factors Affecting Platelet Concentration in Platelet Concentrates from Canine
Blood Donors.
AB - BACKGROUND: Physiologic factors in dogs that might contribute to enhanced
platelet yield in platelet concentrates (PCs) are largely unknown. OBJECTIVE: To
determine whether individual differences in weight, age, preprocessing blood
chemistry, and CBC variables predict the final platelet concentrations in PCs.
Our hypotheses were (1) increased lipemic indices would be positively associated
with increased platelet concentrations in PCs and (2) increased preprocessing
platelet concentrations would be associated with higher platelet concentrations
in the PCs. ANIMALS: All blood donation records of dogs from February 2, 2009
through April 1, 2015 at the University of California-Davis Veterinary Blood Bank
were examined with 104 cases included in this study. METHODS: In this
retrospective study, data were collected from medical records of canine blood
donors. Records were reviewed for internal consistency and accuracy and subjects
were included in the study if donor screening and donation occurred on the same
day and a viable PC was obtained. Univariate and multivariable regressions were
used to test the impact that each variable had on the final platelet
concentration in PCs. RESULTS: Final platelet concentration in PCs was positively
associated with the predonation CBC platelet values (P < .001), lipemic index (P
= .01), and phosphorous levels (P = .001). Collectively these 3 variables
explained 29% of the variance in platelet concentrations in PCs. CONCLUSIONS AND
CLINICAL IMPORTANCE: Future prospective studies are required to determine if
canine blood donations from dogs with lipemia yield PCs with higher platelet
concentrations without negatively affecting other blood components.
PMID- 28421627
TI - Impact of microorganisms, humidity, and temperature on the enantioselective
degradation of imazethapyr in two soils.
AB - Imazethapyr (IM) is a chiral herbicide composed of an (-)-R-enantiomer and an (+)
S-enantiomer with differential herbicidal activity. In this study, the effects of
microbial organisms, humidity, and temperature on the selective degradation of
the (-)-R- and (+)-S-enantiomers of IM were determined in silty loam (SL) and
clay loam (CL) soil with different pH values. The (-)-R-enantiomer of IM was
preferentially degraded in two soils under different microorganism, humidity, and
temperature conditions. The average half-lives of R-IM ranged from 43 to 66.1
days and were significantly shorter (P < 0.05) than those of S-IM, which ranged
from 51.4 to 79.8 days. The enantiomer fraction (EF = (+)-S-enantiomer/((-)-R
enantiomer + (+)-S-enantiomer)) values were used to describe the
enantioselectivity of degradation of IM were >0.5 (P < 0.05) in two unsterilized
soils under different humidity and temperature conditions. The highest EF values
were observed at unsterilized CL soil samples under 50% maximum water-holding
capacity (MWHC) and 25 degrees C environmental conditions. The EF values of the
IM enantiomers were significantly higher (P < 0.05) in CL soils (higher pH =
5.81) and were 0.581 (unsterilized) and 0.575 (50% MWHC; 25 degrees C) compared
with those recorded in SL soil (lower pH = 4.85). In addition, this study
revealed that microbial organisms preferentially utilized the more herbicidal
active IM enantiomer.
PMID- 28421628
TI - Comparison of the nephrotoxic effects of iodixanol versus iohexol in patients
with chronic heart failure undergoing coronary angiography or angioplasty.
AB - OBJECTIVES: The aim of this clinical trial is to compare iodixanol with iohexol
for the incidence of contrast-induced nephropathy in patients with chronic heart
failure with reduced ejection fraction who are currently undergoing coronary
angiography or angioplasty. METHODS: The clinical trial included 220 consecutive
patients with chronic heart failure with reduced ejection fraction undergoing
coronary angiography or angioplasty. Study participants were administered either
iodixanol (n = 110) or iohexol (n = 110). The primary study endpoint was the
incidence of contrast-induced nephropathy within 72 h after the procedure. The
secondary endpoints were to determine the peak increase in serum creatinine
levels and Cystatin C, and the peak decrease in estimated glomerular filtration
rate at 72 h post-contrast medium. RESULTS: Baseline demographic and clinical
characteristics of the patients were similar between the two groups. Our study
showed that the overall incidence of contrast induced nephropathy in patients
with chronic heart failure was 20.9%. The incidence of contrast induced
nephropathy was significantly lower in iodixanol group than in iohexol group
(29.1% vs 12.7%, P = 0.041). The peak increase in serum creatinine levels and the
peak decrease in estimated glomerular filtration rate after the procedure were
statistically significant between the two groups. Moreover, there was
statistically significance in the peak increase of Cystatin C levels after the
procedure. CONCLUSIONS: In patients with chronic heart failure with reduced
ejection fraction who are currently undergoing coronary angiography with or
without percutaneous coronary intervention, the iso-osmolar contrast iodixanol
was associated with a lower incidence of contrast induced nephropathy than low
osmolar contrast iohexol.
PMID- 28421629
TI - Synergistic Effect of a Boron-Doped Carbon-Nanotube-Supported Cu Catalyst for
Selective Hydrogenation of Dimethyl Oxalate to Ethanol.
AB - Heteroatom doping is a promising approach to improve the properties of carbon
materials for customized applications. Herein, a series of Cu catalysts supported
on boron-doped carbon nanotubes (Cu/xB-CNTs) were prepared for the hydrogenation
of dimethyl oxalate (DMO) to ethanol. The structure and chemical properties of
boron-doped catalysts were characterized by XRD, TEM, N2 O pulse adsorption, CO
chemisorption, H2 temperature-programmed reduction, and NH3 temperature
programmed desorption, which revealed that doping boron into CNT supports
improved the Cu dispersion, strengthened the interaction of Cu species with the
CNT support, introduced more surface acid sites, and increased the surface area
of Cu0 and especially Cu+ sites. Consequently, the catalytic activity and
stability of the catalysts were greatly enhanced by boron doping. 100 % DMO
conversion and 78.1 % ethanol selectivity could be achieved over the Cu/1B-CNTs
catalyst, the ethanol selectivity of which was almost 1.7 times higher than that
of the catalyst without boron doping. These results suggest that doping CNTs with
boron is an efficient approach to improve the catalytic performance of CNT-based
catalysts for hydrogenation of DMO. The boron-doped CNT-based catalyst with
improved ethanol selectivity and catalytic stability will be helpful in the
development of efficient Cu catalysts supported on non-silica materials for
selective hydrogenation of DMO to ethanol.
PMID- 28421630
TI - The factor structure of dental fear.
AB - There is limited empirical information as to whether or how stimuli associated
with dental fear can be classified into distinct subtypes. The purpose of the
current study was to develop a descriptive framework for the classification of
dental fear. Data were collected using a survey among Dutch twin families (n =
11,771). The sample was randomly divided into two subsamples of, respectively,
5,920 and 5,851 individuals. An exploratory factor analysis (EFA) was performed
on the first subsample to delineate the multidimensional structure of a set of 28
dental-fear-provoking objects and situations. The second sample was used to
confirm the newly derived model using confirmatory factor analysis (CFA). The EFA
yielded a three-factor solution with 70.7% explained variance pertaining to: (i)
invasive treatment or pain; (ii) losing control; and (iii) physical sensations.
The CFA showed an acceptable fit to the data, thereby confirming the stability of
the three-factor structure. There are at least three different subtypes of dental
fear. As these subtypes require a different treatment approach in clinical
practice, it could be important to assess the severity of patients' fear response
along these three dimensions.
PMID- 28421631
TI - Subclinical lower airways correlates of chronic allergic and non-allergic
rhinitis.
AB - The upper and lower airways behave as a physiological and pathophysiological
unit. Subclinical lower airways abnormalities have been described in patients
with rhinitis without asthma. These are expressed as bronchial hyperreactivity,
abnormalities in lung function and bronchial inflammation, likely as a result of
the same phenomenon with systemic inflammatory impact that reaches both the nose
and the lungs, which for unknown reasons does not always have a full clinical
expression. Patients with rhinitis are at increased risk of developing asthma;
therefore, most authors suggest a careful clinical evaluation and monitoring of
these patients, especially if symptoms related to inflammation in the lower
airways are observed. Although current treatments, such as H1-antihistamines,
intranasal steroids and allergen immunotherapy, are quite effective for the
management of rhinitis, it is difficult to prove their capacity to prevent asthma
among subjects with rhinitis. Evidence showing that the treatment of rhinitis has
a favourable impact on indicators of bronchial hyperreactivity and inflammation
among subjects that have no symptoms of asthma is more frequently described. In
this review, we address the frequency and characteristics of lower airway
abnormalities in subjects with rhinitis, both in paediatric and adult
populations, their likely predictive value for the development of asthma and the
possibilities for therapeutic intervention that could modify the risk of subjects
with rhinitis towards presenting asthma.
PMID- 28421632
TI - Rigidly Tethered Bis-phosphoric Acids: Generation of Tunable Chiral Fluorescent
Frameworks and Unexpected Selectivity for the Detection of Ferric Ions.
AB - We describe the straightforward synthesis of a series of bis-phosphoric acids
(R,R)-1 a-d, featuring two chiral 1,1'-binaphthyl-phosphoric acid units that are
tethered by rigid, pi-conjugated linkers. The nature of the linker has a profound
influence on the properties of the bis-phosphoric acids, such as their self
association behavior and their interaction with metal ions. This led to the
identification of one preferred bis-phosphoric acid (R,R)-1 d, which shows
selective fluorescence quenching in the presence of ferric ions (Fe3+ ). Thus,
(R,R)-1 d could be applied for the detection of Fe3+ , even in the presence of a
variety of other metal ions. The chiral nature of the bis-phosphoric acid enables
the interaction with Fe3+ to be followed by CD spectroscopy, providing a
complementary detection mode with the same probe.
PMID- 28421633
TI - Efficacy of Tulathromycin for the Treatment of Foals with Mild to Moderate
Bronchopneumonia.
AB - BACKGROUND: There is conflicting data regarding the efficacy of tulathromycin for
the treatment of foals with bronchopneumonia. HYPOTHESES: Tulathromycin is
effective for the treatment of bronchopneumonia in foals and noninferior to the
combination of azithromycin and rifampin. ANIMALS: A total of 240 foals on a farm
endemic for infections caused by Rhodococcus equi. METHODS: In a controlled,
randomized, and double-blinded clinical trial, foals with ultrasonographic
pulmonary lesions (abscess score 10-15 cm) were allocated to 3 groups: 1
tulathromycin IM q 7 days (n = 80); 2-azithromycin-rifampin, orally q24h (n =
80); or 3-untreated controls (n = 80). Physical examination and thoracic
ultrasonography were performed by individuals unaware of treatment group
assignment. Foals that worsened were considered treatment failures and removed
from the study. RESULTS: The proportion of foals that recovered was significantly
higher for foals treated with tulathromycin (70 of 79) or azithromycin-rifampin
(76 of 80) compared to that of control foals (22 of 80). The difference in the
percentage of efficacy of azithromycin-rifampin versus tulathromycin was 6.4%
(90% CI = -0.72-13.5%). Given that the confidence interval crossed the
predetermined noninferiority limit of 10%, the null hypothesis that the response
rate in the azithromycin-rifampin group is superior to that of the tulathromycin
group could not be rejected. Resolution of ultrasonographic lesions occurred
faster in foals treated with azithromycin-rifampin than in foals treated with
tulathromycin. CONCLUSION AND CLINICAL IMPORTANCE: Tulathromycin was effective
for the treatment of bronchopneumonia in foals at this farm but not as effective
as the combination of azithromycin-rifampin.
PMID- 28421634
TI - Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel
disease.
AB - Inflammatory bowel disease (IBD), that is Crohn's disease (CD) and ulcerative
colitis, affects about 1.5 million persons in the USA and 2.2 million in Europe.
The pathophysiology of IBD involves immunological, genetic and environmental
factors. The treatment is medico-surgical but suspensive. Anti-TNFalpha agents
have revolutionized the treatment of IBD but have side effects. In addition, a
non-negligible percentage of patients with IBD stop or take episodically their
treatment. Consequently, a nondrug therapy targeting TNFalpha through a
physiological pathway, devoid of major side effects and with a good cost
effectiveness ratio, would be of interest. The vagus nerve has dual anti
inflammatory properties through its afferent (i.e. hypothalamic-pituitary-adrenal
axis) and efferent (i.e. the anti-TNFalpha effect of the cholinergic anti
inflammatory pathway) fibres. We have shown that there is an inverse relationship
between vagal tone and plasma TNFalpha level in patients with CD, and have
reported, for the first time, that chronic vagus nerve stimulation has anti
inflammatory properties in a rat model of colitis and in a pilot study performed
in seven patients with moderate CD. Two of these patients failed to improve after
3 months of vagus nerve stimulation but five were in deep remission (clinical,
biological and endoscopic) at 6 months of follow-up and vagal tone was restored.
No major side effects were observed. Thus, vagus nerve stimulation provides a new
therapeutic option in the treatment of CD.
PMID- 28421635
TI - A Homochiral {CoIotaIota16 CoIotaIotaIota4 } Supertetrahedral T4 Cluster from a
Racemic Ligand with Ferromagnetic Behavior and High Photocatalytic Activity.
AB - A homochiral mixed-valence cobalt cluster [CoIotaIota16 CoIotaIotaIota4 (MU6 -O)4
(MU3 -OH)12 (S-bme)12 (OAc)6 ]Cl6 ?5 CH3 OH?18 H2 O (1, Hbme=1H-(benzimidazol-2
yl)ethanol) was synthesized from a racemic ligand and three cobalt salts of CoCl2
?6 H2 O, Co(Ac)2 ?4 H2 O and Co(NO3 )2 ?6 H2 O in a DMF/MeOH mixed solvent. The
enantioselective coordination occurs when a large excess of cobalt ions added in
the solution and only the S-configuration of the racemic ligand involved in
crystallization. The CD spectra of three crystal samples show identical Cotton
signals, indicating the repeatability and the enantiomeric purity of the single
crystals. This compound presents a beautiful two-shell Matryoshka-type
supertetrahedral T4 cluster constructed by an inner CoIotaIotaIota4 O4 cubane and
four exterior CoIotaIota4 O4 cubanes bridged by MU6 -O2- and MU3 -OH- ions. This
highest nuclear chiral cobalt cluster is the first example of enantiopure cobalt
cluster separated from a racemic ligand and is the largest supertetrahedral
cobalt cluster up to now. The magnetic studies reveal it behaves as a
ferromagnet. Photocatalytic properties of 1 show high catalytic activities for
the degradation of the highly toxic triphenyl dye crystal violet (CV) in the
presence of H2 O2 under visible light in aqueous solution. The degradation rate
almost reach 100 % at 45 min and can maintain 98.54 % after 8 cycles.
PMID- 28421636
TI - Leveraging cell type specific regulatory regions to detect SNPs associated with
tissue factor pathway inhibitor plasma levels.
AB - Tissue factor pathway inhibitor (TFPI) regulates the formation of intravascular
blood clots, which manifest clinically as ischemic heart disease, ischemic
stroke, and venous thromboembolism (VTE). TFPI plasma levels are heritable, but
the genetics underlying TFPI plasma level variability are poorly understood.
Herein we report the first genome-wide association scan (GWAS) of TFPI plasma
levels, conducted in 251 individuals from five extended French-Canadian Families
ascertained on VTE. To improve discovery, we also applied a hypothesis-driven
(HD) GWAS approach that prioritized single nucleotide polymorphisms (SNPs) in (1)
hemostasis pathway genes, and (2) vascular endothelial cell (EC) regulatory
regions, which are among the highest expressers of TFPI. Our GWAS identified 131
SNPs with suggestive evidence of association (P-value < 5 * 10-8 ), but no SNPs
reached the genome-wide threshold for statistical significance. Hemostasis
pathway genes were not enriched for TFPI plasma level associated SNPs (global
hypothesis test P-value = 0.147), but EC regulatory regions contained more TFPI
plasma level associated SNPs than expected by chance (global hypothesis test P
value = 0.046). We therefore stratified our genome-wide SNPs, prioritizing those
in EC regulatory regions via stratified false discovery rate (sFDR) control, and
reranked the SNPs by q-value. The minimum q-value was 0.27, and the top-ranked
SNPs did not show association evidence in the MARTHA replication sample of 1,033
unrelated VTE cases. Although this study did not result in new loci for TFPI, our
work lays out a strategy to utilize epigenomic data in prioritization schemes for
future GWAS studies.
PMID- 28421637
TI - A New Approach to Models of the 4,5-Dihydroxycyclopentenone Core of the
Kodaistatins A-D: Elucidation of the Diol Configuration in Kodaistatin A.
AB - The kodaistatins A-D are strongly anti-diabetic natural products from Aspergillus
terreus that hold some promise of a novel diabetes cure. However, considerations
of that kind face two drawbacks: 1) The kodaistatins A-D contain a heavily
substituted pulvinone/cyclopentenone combination; 2) they are 1,2-diols, the 3D
structures of which have not been assigned yet. However, we can exclude two of
the four possible stereostructures. We conclude that kodaistatin A is a trans-,
not a cis-diol from NMR comparisons with a pair of cis, trans-isomeric
kodaistatin models, which we synthesized in 11 and 12 steps, respectively. The
stereocenters of the diol moiety arose from stereocomplementary, highly
diastereoselective aldol additions of a lithium enolate or the corresponding
silyl ketene acetal. The cyclopentenone moieties stemmed from intramolecular
aldol additions and ensuing dehydrations. The requisite enolates were obtained by
the reduction of alpha-bromoketones with samarium diiodide.
PMID- 28421638
TI - Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced
Chronic Kidney Disease.
AB - Each year approximately 13,000 Veterans transition to maintenance dialysis,
mostly in the traditional form of thrice-weekly hemodialysis from the start.
Among >6000 dialysis units nationwide, there are currently approximately 70
Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers
and their limited capacity, only 10% of all incident dialysis Veterans initiate
treatment in a VA center. Evidence suggests that, among Veterans, the receipt of
care within the VA system is associated with favorable outcomes, potentially
because of the enhanced access to healthcare resources. Data from the United
States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest
that Veterans who receive dialysis in a VA unit exhibit greater survival compared
with the non-VA centers. Substantial financial expenditures arise from the high
volume of outsourced care and higher dialysis reimbursement paid by the VA than
by Medicare to outsourced providers. Given the exceedingly high mortality and
abrupt decline in residual kidney function (RKF) in the first dialysis year, it
is possible that incremental transition to dialysis through an initial twice
weekly hemodialysis regimen might preserve RKF, prolong vascular access
longevity, improve patients' quality of life, and be a more patient-centered
approach, more consistent with "personalized" dialysis. Broad implementation of
incremental dialysis might also result in more Veterans receiving care within a
VA dialysis unit. Controlled trials are needed to examine the safety and efficacy
of incremental hemodialysis in Veterans and other populations; the administrative
and health care as well as provider structure within the VA system would
facilitate the performance of such trials.
PMID- 28421639
TI - Cilostazol adjunctive therapy in treatment of negative symptoms in chronic
schizophrenia: Randomized, double-blind, placebo-controlled study.
AB - OBJECTIVE: To evaluate the efficacy and safety of cilostazol, a selective
inhibitor of phosphodiesterase III, as an adjunctive to risperidone in
alleviating the negative symptoms of schizophrenia. METHODS: Eighty-four in
patients with diagnosis of chronic schizophrenia participated in a randomized,
placebo-controlled trial and underwent 8 weeks of treatment with either
cilostazol (50 mg twice a day) or placebo as an adjuvant to risperidone.
Participants were assessed using the positive and negative syndrome scale (PANSS)
at baseline and at weeks 2, 4, 6, and 8. The primary outcome measure of the trial
was to evaluate the efficacy of cilostazol compared to placebo in improving the
PANSS negative subscale score. RESULT: General linear model repeated measures
demonstrated significant effect for time * treatment interaction on negative
subscale scores (p < .001) and PANSS total (p = .006) but did not demonstrate
significant effect on the PANSS positive (p = .37) and general (p = .06)
subscales. Frequency of adverse events was not significantly different between
the 2 treatment groups. No serious adverse event was observed. CONCLUSION: An 8
week course of treatment with cilostazol as an adjunct to risperidone showed a
favorable safety and efficacy profile in patients with schizophrenia.
PMID- 28421640
TI - Identification of risk factors predicting febrile neutropenia in patients with
metastatic germ cell tumors receiving cisplatin-based combination chemotherapy.
AB - OBJECTIVES: To identify clinical features and predictive factors of febrile
neutropenia in Japanese patients with metastatic germ cell tumors undergoing
cytotoxic chemotherapy. METHODS: Between April 2007 and May 2016, 86 consecutive
Japanese patients with metastatic germ cell tumors were treated with cisplatin
based combination chemotherapy, including bleomycin, etoposide and cisplatin, and
paclitaxel, ifosfamide and cisplatin. A total of 378 chemotherapy cycles
administered for these 86 patients were retrospectively analyzed. RESULTS: During
the 378 cycles, consisting of 212 for bleomycin, etoposide and cisplatin, and 166
for paclitaxel, ifosfamide and cisplatin, 81 episodes of febrile neutropenia
(21.4%) developed in 34 patients (39.5%). Multivariate logistic regression
analysis showed that low estimated glomerular filtration rate and albumin levels
were independent risk factors for the development of febrile neutropenia.
Furthermore, a significant difference in the incidence of febrile neutropenia was
noted according to positive numbers of these two independent risk factors; that
is, febrile neutropenia occurred in 13 of 171 courses in patients negative for
any risk factors (7.6%), 44 of 155 courses in those positive for a single risk
factor (28.4%) and 24 of 52 courses in those positive for two risk factors
(46.2%). CONCLUSIONS: The incidence of febrile neutropenia in Japanese metastatic
germ cell tumor patients receiving cisplatin-based combination chemotherapy
appears to be higher than reported previously by studies in Western countries.
When carrying out cytotoxic chemotherapy, special attention should be paid to
patients with low estimated glomerular filtration rate and/or albumin levels
considering the high probability of febrile neutropenia.
PMID- 28421641
TI - It is not just about occupation, but also about where you work.
AB - OBJECTIVES: Dentistry is characterized by a meaningful but also stressful
psychosocial working environment. Job satisfaction varies among staff working
under different organizational forms. The aim of this study was to identify (i)
to what extent crucial psychosocial work environment characteristics differ among
occupations in general public dental clinics in Sweden, and (ii) how much of the
variation within each occupation is attributable to the organizational level.
METHODS: All staff (N=1782) employed in four public dental organizations received
an email with personal log-in to an electronic questionnaire based on the
Copenhagen Psychosocial Questionnaire. After two reminders, a response rate of
75% was obtained. Responses from 880 nonmanagerial dentists, dental hygienists
and dental nurses working in general practices were included in our analyses.
RESULTS: First, we compared the three dental occupations. We found that job
demands, task resources (eg influence, possibilities for development and role
clarity), strain symptoms and attitudes to work differed among occupations,
dentists having the least favourable situation. Next, we compared the four
organizations for each occupational group, separately. For dentists, a
significant and relevant amount of variance (P<.05 and ICC >.05) was explained by
the organizational level for 15 of 26 subscales, least pronounced for task
resources. By contrast, for dental nurses and hygienists, the corresponding
number was 2 subscales of 26. The psychosocial working environment of people
working at the organization with the highest levels of strain indicators and the
least positive work-related attitudes differed systematically from the
organization with the most favourable profile, in particular regarding job
demands and leadership aspects. CONCLUSION: In conclusion, the psychosocial
working environment depended to a large degree on occupation and, for dentists in
particular, also on their organizational affiliation. The findings suggest a
potential for designing interventions at organizational level for improvements of
the psychosocial working environment for dentists.
PMID- 28421642
TI - How do we know what makes for "best practice" in clinical supervision for
psychological therapists? A content analysis of supervisory models and
approaches.
AB - : Clinical supervision for psychotherapies is widely used in clinical and
research contexts. Supervision is often assumed to ensure therapy adherence and
positive client outcomes, but there is little empirical research to support this
contention. Regardless, there are numerous supervision models, but it is not
known how consistent their recommendations are. This review aimed to identify
which aspects of supervision are consistent across models, and which are not. A
content analysis of 52 models revealed 71 supervisory elements. Models focus more
on supervisee learning and/or development (88.46%), but less on emotional aspects
of work (61.54%) or managerial or ethical responsibilities (57.69%). Most models
focused on the supervisee (94.23%) and supervisor (80.77%), rather than the
client (48.08%) or monitoring client outcomes (13.46%). Finally, none of the
models were clearly or adequately empirically based. Although we might expect
clinical supervision to contribute to positive client outcomes, the existing
models have limited client focus and are inconsistent. Therefore, it is not
currently recommended that one should assume that the use of such models will
ensure consistent clinician practice or positive therapeutic outcomes. KEY
PRACTITIONER MESSAGES: There is little evidence for the effectiveness of
supervision. There is a lack of consistency in supervision models. Services need
to assess whether supervision is effective for practitioners and patients.
PMID- 28421643
TI - Empiric antibiotic regimens for neonatal sepsis in Australian and New Zealand
neonatal intensive care units.
AB - AIM: Neonatal sepsis remains an important cause of morbidity and mortality, and
requires prompt empiric treatment. However, only a minority of babies who receive
antibiotics for suspected sepsis have an infection. Antimicrobial exposure in
infancy has important short- and long-term consequences. There is no consensus
regarding empirical antimicrobial regimens. METHODS: The study included a survey
of empiric antimicrobial regimens in all tertiary neonatal intensive care units
in Australia and New Zealand in 2013-2014. RESULTS: All 27 units responded. For
early-onset sepsis, all units used a combination of gentamicin with either
penicillin or ampicillin. For late-onset sepsis, the frequency of units using
empiric vancomycin (41%) versus empiric flucloxacillin (48%) was similar.
Gestational age or the presence of a central venous catheter had little influence
on using vancomycin instead of flucloxacillin. For late-onset sepsis with
meningitis there was marked variation in antimicrobial combinations, with 15
different regimens described. A total of 93% used a cefotaxime-based regimen,
either as monotherapy (22%) or combined with a second (22%) or third (48%) agent.
For suspected necrotising enterocolitis, 89% used an aminoglycoside,
metronidazole and a penicillin. Historical outbreaks of multi-resistant organisms
exerted long-term influence over regimen choice. CONCLUSIONS: There was limited
use of broad-spectrum agents such as carbapenems or third-generation
cephalosporins. In this region with low methicillin-resistant Staphylococcus
aureus prevalence, empiric vancomycin use was common, selected for activity
against coagulase-negative staphylococci. Empiric vancomycin is rarely necessary
because coagulase-negative staphylococci are often contaminants and sepsis is
rarely fulminant, occurring almost exclusively in extremely low birthweight
infants. Implementation of appropriate, local antimicrobial policies is crucial
to minimise antimicrobial exposure in this vulnerable population and halt the
development of antimicrobial resistance.
PMID- 28421644
TI - The clinical application of suicide risk assessment: A theory-driven approach.
AB - : The interpersonal theory of suicide posits that thwarted belongingness (TB) and
perceived burdensomeness (PB) increase suicide ideation; however, studies have
found mixed results regarding this hypothesis among psychiatric inpatients. This
study aimed to (a) demonstrate how assessing TB and PB using the Interpersonal
Needs Questionnaire (INQ) can provide clinically useful information and (b)
investigate how statistical methodology may impact the clinical application of
the INQ. Participants were 139 (Sample 1) and 104 (Sample 2) psychiatric
inpatients. In both samples, ordinal logistic regression results indicated TB and
PB, separately, were significant predictors of suicide ideation-related outcomes;
however, when examined as simultaneous predictors, TB was no longer a significant
predictor. The interaction between TB and PB was not significant for either
sample. Despite this, TB and PB scores provided clinically relevant information
about suicide ideation-related outcomes. For example, the highest scores on TB
and PB indicated a 93% and 95% chance of having some level of distress due to
suicide ideation (Sample 1), a 91% and 92% chance of having some level of desire
for death, and a 79% and 84% chance of having some level of desire for suicide,
respectively (Sample 2). This study also proposes clinical cutoff scores for the
INQ (for TB and PB, respectively, cutoff scores were 22 and 17 for distress due
to suicide ideation, 33 and 17 for desire for death, and 31 and 22 for desire for
suicide). Although these results indicate that multicollinearity between TB and
PB may create interpretational ambiguity for clinicians, TB and PB may each be
useful separate predictors of suicide ideation-related outcomes in psychiatric
inpatient settings and should be incorporated into suicide risk assessment. KEY
PRACTITIONER MESSAGE: The 15-item Interpersonal Needs Questionnaire (an
assessment of thwarted belongingness and perceived burdensomeness) should be
incorporated into suicide risk assessment. Among psychiatric inpatients, greater
thwarted belongingness and perceived burdensomeness, as separate predictors, were
associated with increased levels of distress due to suicide ideation, desire for
death, and desire for suicide. The highest scores on thwarted belongingness and
perceived burdensomeness indicated a 79% to 95% chance of experiencing an
elevated level of distress due to suicide ideation, desire for death, or desire
for suicide. Recommended clinical cutoff scores were provided. For example,
thwarted belongingness cutoff score of 31 and perceived burdensomeness cutoff
score of 22 maximized the sensitivity and specificity of the INQ to detect some
level of desire for suicide.
PMID- 28421645
TI - Grammaticality differences between Spanish-speaking children with specific
language impairment and their typically developing peers.
AB - BACKGROUND: A limited number of studies have analyzed grammaticality in
monolingual Spanish-speaking children with specific language impairment (SLI).
Most of the available data are based on bilingual speakers. AIMS: To extend
previous studies by doing a more detailed analysis of grammatical types in
monolingual Spanish-speakers with and without SLI. METHODS & PROCEDURES: Forty
nine Spanish-speaking children (18 with SLI, 17 age-matched typically developing
controls, 14 language-matched controls) were recruited from schools in Mexico and
observed in a spontaneous narrative task. OUTCOMES & RESULTS: The findings were
inconsistent with those of previous studies. Significant differences were found
for article, connector and preposition omissions, and the per cent of
ungrammatical utterances. There were no significant differences found for clitics
and verb phrases, though clitic substitutions were frequent. Language-matched
controls did not produce different frequencies of ungrammatical utterances.
CONCLUSIONS & IMPLICATIONS: Significant differences were found for three main
items: the per cent of ungrammatical utterances, the omission of articles and the
omission of prepositions. Therefore, we propose these components be taken into
consideration when distinguishing typically developing children from children
with SLI.
PMID- 28421646
TI - Increasing adolescents' depth of understanding of cross-curriculum words: an
intervention study.
AB - BACKGROUND: There is some evidence that vocabulary intervention is effective for
children, although further research is needed to confirm the impact of
intervention within contexts of social disadvantage. Very little is known about
the effectiveness of interventions to increase adolescent knowledge of cross
curriculum words. AIMS: To evaluate the effectiveness of an intervention
programme designed to develop adolescents' knowledge of cross-curriculum words.
METHODS & PROCEDURES: Participants were 35 adolescents aged between 12 and 14
years who were at risk of educational underachievement with low scores on a range
of assessments. Participants received a 10-week intervention programme in small
groups, targeting 10 cross-curriculum words (e.g., 'summarize'). This was
evaluated using a bespoke outcome measure (the Word Knowledge Profile). The study
involved an AABA design, with a repeated baseline, delayed intervention cohort
and blind assessment. Intervention included both semantic and phonological
information about the target words and involved the adolescents using the words
in multiple contexts. OUTCOMES & RESULTS: Results were promising and
participants' knowledge of the targeted words significantly increased following
intervention. Progress was demonstrated on the Word Knowledge Profile on the item
requiring participants to define the word (for the summer intervention group
only). This increase in depth of knowledge was seen on taught words but not on
matched non-taught words. CONCLUSIONS & IMPLICATIONS: Cross-curriculum words are
not consistently understood by adolescents at risk of low educational attainment
within a low socio-economic context. A 10-week intervention programme resulted in
some increases to the depth of knowledge of targeted cross-curriculum words.
PMID- 28421647
TI - Evaluation of magnetic resonance imaging for the differentiation of inflammatory,
neoplastic, and vascular intradural spinal cord diseases in the dog.
AB - Magnetic resonance imaging (MRI) is a common test for dogs with suspected
intradural spinal cord lesions, however studies on diagnostic performance for
this test are lacking. Objectives of this multi-institutional, retrospective,
case-control study were to estimate sensitivity and specificity of MRI for (1)
distinguishing between histopathologically confirmed intradural spinal cord
disease versus degenerative myelopathy in dogs, (2) categorizing intradural
spinal cord diseases as neoplastic, inflammatory, or vascular; and (3)
determining tumor type within the etiologic category of neoplasia. Additional
aims were to (1) determine whether knowledge of clinical data affects sensitivity
and specificity of MRI diagnoses; and (2) report interrater agreement for MRI
classification of intradural spinal lesions. Cases were recruited from
participating hospital databases over a 7-year period. Three reviewers
independently evaluated each MRI study prior to and after provision of clinical
information. A total of 87 cases were sampled (17 degenerative myelopathy, 53
neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had
excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions
but specificity varied before and after provision of clinical data (68.6% vs.
82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and
moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower
for classifying inflammatory lesions but improved with provision of clinical data
(48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for
diagnosing vascular lesions (25.0%). Interrater agreement was very good for
correctly diagnosing dogs with intradural lesions (K = 0.882-0.833), and good (K
= 0.726-0.671) for diagnosing dogs with neoplasia.
PMID- 28421648
TI - Placebo-like analgesia via response imagery.
AB - BACKGROUND: Placebo effects on pain are reliably observed in the literature. A
core mechanism of these effects is response expectancies. Response expectancies
can be formed by instructions, prior experiences and observation of others.
Whether mental imagery of a response can also induce placebo-like expectancy
effects on pain has not yet been studied systematically. METHODS: In Study 1, 80
healthy participants were randomly allocated to (i) response imagery or (ii)
control imagery. In Study 2, 135 healthy participants were randomly allocated to
(i) response imagery with a verbal suggestion regarding its effectiveness, (ii)
response imagery only, or (iii) no intervention. In both studies, expected and
experienced pain during cold pressor tests were measured pre- and post
intervention, along with psychological and physiological measures. RESULTS:
Participants rated pain as less intense after response imagery than after control
imagery in Study 1 (p = 0.044, etap2 = 0.054) and as less intense after response
imagery (with or without verbal suggestion) than after no imagery in Study 2 (p <
0.001, etap2 = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068,
etap2 = 0.038). The effects of response imagery on experienced pain were mediated
by expected pain. CONCLUSIONS: Thus, in line with research on placebo effects,
the current findings indicate that response imagery can induce analgesia, via its
effects on response expectancies. SIGNIFICANCE: The reported studies extend
research on placebo effects by demonstrating that mental imagery of reduced pain
can induce placebo-like expectancy effects on pain.
PMID- 28421649
TI - Decreased expression of EphA5 is associated with Fuhrman nuclear grade and
pathological tumour stage in ccRCC.
AB - The incidence of renal cell carcinoma is increasing all over the world. The
molecular mechanisms for tumorigenesis, progression and prognosis are still
unknown. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors
have been reported to be expressed aberrantly in many types of human cancers and
in particular EphA5 may play a role in certain human cancers. In this study, a
set of clear cell renal cell carcinoma (ccRCC) tissues were subjected to
immunohistochemistry. The relationship between EphA5 protein expression and
clinicopathological parameters was statistically analysed. Our data show that
EphA5 protein was negatively (0) or weakly (1+) expressed in 48 of 78 (61.5%),
moderately (2+) expressed in 15 of 78 (19.2%) and strongly (3+) expressed in 15
of 78 (19.2%) tumour samples of ccRCC. Decreased expression of EphA5 was detected
more often in females than in males (P = 0.017, rs = -0.267). Expression of
EphA5 was related negatively to Fuhrman grade (P = 0.013, rs = -0.279) and
pathological tumour stage pT (P = 0.003, rs = -0.334). No relation between the
expression of EphA5 and age of patients was found (P = 0.107, rs = 0.184).
Fuhrman grade and pT stage are the most important factors used in prognosis of
ccRCC. Hence this study may provide a new and useful prognostic marker in the
clinical practice of ccRCC.
PMID- 28421650
TI - Keeping Up With the Kids: Diffusion of Innovation in Pediatric Emergency Medicine
Among Emergency Physicians.
PMID- 28421652
TI - Corrigendum.
PMID- 28421651
TI - Self-management of first trimester medical termination of pregnancy: a
qualitative study of women's experiences.
AB - OBJECTIVE: To explore the experiences of women in Scotland who return home to
complete medical termination of pregnancy (TOP) <=63 days of gestation, after
being administered with mifepristone and misoprostol at an NHS TOP clinic.
DESIGN: Qualitative interview study. SETTING: One National Health Service health
board (administrative) area in Scotland. POPULATION OR SAMPLE: Women in Scotland
who had undergone medical TOP <=63 days, and self-managed passing the pregnancy
at home; recruited from three clinics in one NHS health board area between
January and July 2014. METHODS: In-depth, semi-structured interviews with 44
women in Scotland who had recently undergone TOP <=63 days of gestation, and who
returned home to pass the pregnancy. Data were analysed thematically using an
approach informed by the Framework method. MAIN OUTCOME MEASURES: Women's
experiences of self-management of TOP <=63 days of gestation. RESULTS: Key themes
emerging from the analysis related to self-administration of misoprostol in
clinic; reasons for choosing home self-management; facilitation of self
management and expectation-setting; experiences of getting home; self-managing
and monitoring treatment progress; support for self-management (in person and
remotely); and pregnancy self-testing to confirm completion. CONCLUSIONS:
Participants primarily found self-administration of misoprostol and home self
management to be acceptable and/or preferable, particularly where this was
experienced as a decision made jointly with health professionals. The way in
which home self-management is presented to women at clinic requires ongoing
attention. Women could benefit from the option of home administration of
misoprostol. TWEETABLE ABSTRACT: Women undergoing medical TOP 63 days found home
self-management to be acceptable and/or preferable.
PMID- 28421653
TI - Permethrin and malathion LD90 values for Culex quinquefasciatus vary with topical
application site.
AB - Prior research in multiple insect species has demonstrated that insecticide
induced mortality varies according to the body region exposed on the insect. This
variation has been demonstrated in Culex quinquefasciatus Say (Diptera:
Culicidae), but has not been quantified using dose-response curves. Applications
of technical permethrin or malathion to one of three body regions on Cx.
quinquefasciatus resulted in dose-response curves that were not equivalent to one
another. The generated LD90 values and curves for each body region were compared
with previously reported LD values for analogous sites in several mosquito
species, specifically the mesothorax. Based on the present results, the
permethrin and malathion LD50 and LD90 concentrations required for droplets
impinging on the abdomen and mesothorax of Cx. quinquefasciatus when applied
through ground-based spray systems utilized by mosquito control programmes were
calculated.
PMID- 28421655
TI - Reduction of preterm birth rates starts at preconception.
PMID- 28421654
TI - Short-term outcomes of small incision cataract surgery provided by a regional
population in the Pacific.
AB - BACKGROUND: This study aims to describe patient demographics, visual and surgical
outcomes of a cohort undergoing small incision cataract surgery at a Pacific
regional ophthalmic training facility. DESIGN: This is a prospective,
longitudinal study conducted at the Pacific Eye Institute, Fiji. PARTICIPANTS:
One hundred fifty-six patients underwent small incision cataract surgery.
METHODS: Preoperatively, a complete ophthalmic examination, including pachymetry
and macular optical coherence tomography performed by two independent
investigators. Temporal small incision cataract surgery with intraocular lens
insertion was performed by ophthalmologists, and trainee ophthalmologists. Follow
up occurred at day one, four weeks and 3 months. MAIN OUTCOME MEASURES: Patient
characteristics, visual outcomes including surgically induced astigmatism and
complications. RESULTS: Ninety-one per cent (142/156) attended 3-month follow-up
with median age 63 years (range 19-82), 52% female (81/156) and 58% (90/156)
Fijian ethnicity. In 37% (57/156), the contralateral eye was pseudophakic. Mean
preoperative best spectacle-corrected visual acuity was logMAR 1.44 (6/165). At 3
months, 74% (105/142) achieved >=6/18 unaided vision (94% [133/142] best
spectacle-corrected visual acuity). Mean postoperative spherical equivalent was
0.78 (SD 0.95) D and mean surgically induced astigmatism 1.04 (0.57) D.
Complications included posterior capsular rupture with vitreous loss (4%
[6/156]), optical coherence tomography confirmed macular oedema (8% [12/152] at 4
weeks), significant posterior capsular opacity (23% [31/136]) and >5% increase in
preoperative pachymetry (1% [1/142]) at 3 months. Reduction in preoperative best
spectacle-corrected visual acuity occurred in 2% (3/142). No cases of
endophthalmitis. CONCLUSION AND RELEVANCE: Small incision cataract surgery
provided to a regional population is effective with 94% achieving the World
Health Organisation's definition of 'Good Vision' (>=6/18). Refinements in
biometric and surgical techniques may allow a greater proportion of patients to
achieve good unaided vision.
PMID- 28421656
TI - Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and
wrinkling: A randomized, double-blind, and placebo-controlled study.
AB - BACKGROUND: Photoaging is a severe skin damage that occurs as a result of
exposure to external elements, primarily ultraviolet (UV) irradiation.
Chronically, UV-irradiated skin exhibits the signs of sunburn and
hyperpigmentation with the destruction of connective tissues. Previously,
Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed
antiphotoaging activities in vitro and in vivo. OBJECTIVE: The aim of this study
was to investigate the clinical efficacy of B. pandurata intake on skin
hydration, gloss, wrinkling, and elasticity. METHODS: A double-blind, placebo
controlled trial was conducted to clinically evaluate the effect of B. pandurata
ethanol extract (BPE) containing 8% of panduratin A on human skin hydration,
gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to
receive tablets containing either BPE or placebo for 12 weeks. RESULTS: The test
group had significantly increased skin hydration and gloss and decreased
wrinkling compared to the placebo group at 12 weeks. There was no significant
difference in skin elasticity between the two groups; however, the increment rate
in the test group was higher than that in the placebo group at 12 weeks. None of
the subjects developed adverse symptoms during the study period. CONCLUSION:
These results suggest that BPE can be used as a nutraceutical or nutricosmetic
material for improving human skin hydration, gloss, and wrinkling.
PMID- 28421657
TI - Core outcome sets in women's and newborn health: a systematic review.
AB - BACKGROUND: Variation in outcome collection and reporting is a serious hindrance
to progress in our specialty; therefore, over 80 journals have come together to
support the development, dissemination, and implementation of core outcome sets.
OBJECTIVE: This study systematically reviewed and characterised registered,
progressing, or completed core outcome sets relevant to women's and newborn
health. SEARCH STRATEGY: Systematic search using the Core Outcome Measures in
Effectiveness Trial initiative and the Core Outcomes in Women's and Newborn
Health initiative databases. SELECTION CRITERIA: Registry entries, protocols,
systematic reviews, and core outcome sets. DATA COLLECTION AND ANALYSIS:
Descriptive statistics to describe characteristics and results. RESULTS: There
were 49 core outcome sets registered in maternal and newborn health, with the
majority registered in 2015 (n = 22; 48%) or 2016 (n = 16; 32%). Benign
gynaecology (n = 8; 16%) and newborn health (n = 3; 6%) are currently under
represented. Twenty-four (52%) core outcome sets were funded by international (n
= 1; <1%), national (n = 18; 38%), and regional (n = 4; 8%) bodies. Seven
protocols were published. Twenty systematic reviews have characterised the
inconsistency in outcome reporting across a broad range of relevant healthcare
conditions. Four core outcome sets were completed: reconstructive breast surgery
(11 outcomes), preterm birth (13 outcomes), epilepsy in pregnancy (29 outcomes),
and maternity care (48 outcomes). The quantitative, qualitative, and consensus
methods used to develop core outcome sets varied considerably. CONCLUSIONS: Core
outcome sets are currently being developed across women's and newborn health,
although coverage of topics is variable. Development of further infrastructure to
develop, disseminate, and implement core outcome sets is urgently required.
TWEETABLE ABSTRACT: Forty-nine women's and newborn core outcome sets registered.
50% funded. 7 protocols, 20 systematic reviews, and 4 core outcome sets
published. @coreoutcomes @jamesmnduffy.
PMID- 28421658
TI - Transcriptional signatures of connectomic subregions of the human striatum.
AB - Functionally distinct regions of the brain are thought to possess a
characteristic connectional fingerprint - a profile of incoming and outgoing
connections that defines the function of that area. This observation has
motivated efforts to subdivide brain areas using their connectivity patterns.
However, it remains unclear whether these connectomically-defined subregions can
be distinguished at the molecular level. Here, we combine high-resolution
diffusion-weighted magnetic resonance imaging with transcriptomic data to show
that connectomically-defined subregions of the striatum carry distinct
transcriptional signatures. Using data-driven clustering of diffusion
tractography, seeded from the striatum in 100 healthy individuals, we identify a
tripartite organization of the caudate and putamen that comprises ventral, dorsal
and caudal subregions. We then use microarray data of gene expression levels in
19 343 genes, taken from 98 tissue samples distributed throughout the striatum,
to accurately discriminate the three connectomically-defined subregions with 80
90% classification accuracy using linear support vector machines. This
classification accuracy was robust at the group and individual level and was
superior for our parcellation of the striatum when compared with parcellations
based on anatomical boundaries or other criteria. Genes contributing strongly to
classification were enriched for gene ontology categories including dopamine
signaling, glutamate secretion, response to amphetamine and metabolic pathways,
and were implicated in risk for disorders such as schizophrenia, autism and
Parkinson's disease. Our findings highlight a close link between regional
variations in transcriptional activity and inter-regional connectivity in the
brain, and suggest that there may be a strong genomic signature of
connectomically-defined subregions of the brain.
PMID- 28421659
TI - The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated
with autophagy induction through cAMP signaling.
AB - SCOPE: Although the previous trials of inflammation have indicated that morin
hydrate (MO) hold considerable promise, understanding the distinct mechanism of
MO against inflammation remains a challenge. METHODS AND RESULTS: This study
investigated the effect of MO in atherosclerosis in ApoE-/- mice and underlying
cell signaling of MO effect in inflammation in human umbilical vein endothelial
cells (HUVECs). Administration of MO significantly reduced serum lipid level,
inflammatory cytokines (TNF-alpha and ICAM-1), and atherosclerotic plaque
formation in vivo. MO presence attenuated the expression of TNF-alpha-induced
inflammatory cytokines (ICAM-1, COX-2, and MMP-9), and remarkably enhanced
microtubule associated protein 1 light chain 3 beta 2 (MAP1LC3B2) expression and
sequestosome 1 (SQSTM1/p62) degradation in HUVECs. These MO effects were
significantly prevented by the presence of autophagic inhibitors, 3-methyladenine
(3-MA), or chloroquine (CQ), as well as siRNA suppression of ATG5 and BECN1. MO
increased intracellular cAMP levels and activated cAMP-PKA-AMPK-SIRT1 signaling
in vivo and in vitro. These changes resulted in increased expression of autophagy
related protein MAP1LC3B2 and decreased secretion of inflammatory cytokines (ICAM
1, COX-2, and MMP-9). CONCLUSION: Our results suggest that anti-AS and anti
inflammatory effects of MO are largely associated with its induction of autophagy
through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway.
PMID- 28421660
TI - Biocatalytic Asymmetric Phosphorylation Catalyzed by Recombinant Glycerate-2
Kinase.
AB - The efficient synthesis of pure d-glycerate-2-phosphate is of great interest due
to its importance as an enzyme substrate and metabolite. Therefore, we
investigated a straightforward one-step biocatalytic phosphorylation of glyceric
acid. Glycerate-2-kinase from Thermotoga maritima was expressed in Escherichia
coli, allowing easy purification. The selective glycerate-2-kinase-catalyzed
phosphorylation was followed by 31 P NMR and showed excellent enantioselectivity
towards phosphorylation of the d-enantiomer of glyceric acid. This
straightforward phosphorylation reaction and subsequent product isolation enabled
the preparation of enantiomerically pure d-glycerate 2-phosphate. This
phosphorylation reaction, using recombinant glycerate-2-kinase, yielded d
glycerate 2-phosphate in fewer reaction steps and with higher purity than
chemical routes.
PMID- 28421661
TI - Safety in psychiatric inpatient care: The impact of risk management culture on
mental health nursing practice.
AB - The discourse of safety has informed the care of individuals with mental illness
through institutionalization and into modern psychiatric nursing practices.
Confinement arose from safety: out of both societal stigma and fear for public
safety, as well as benevolently paternalistic aims to protect individuals from
self-harm. In this paper, we argue that within current psychiatric inpatient
environments, safety is maintained as the predominant value, and risk management
is the cornerstone of nursing care. Practices that accord with this value are
legitimized and perpetuated through the safety discourse, despite evidence
refuting their efficacy, and patient perspectives demonstrating harm. To
illustrate this growing concern in mental health nursing care, we provide four
exemplars of risk management strategies utilized in psychiatric inpatient
settings: close observations, seclusion, door locking and defensive nursing
practice. The use of these strategies demonstrates the necessity to shift
perspectives on safety and risk in nursing care. We suggest that to re-centre
meaningful support and treatment of clients, nurses should provide
individualized, flexible care that incorporates safety measures while also
fundamentally re-evaluating the risk management culture that gives rise to and
legitimizes harmful practices.
PMID- 28421662
TI - The outer membrane vesicles: Secretion system type zero.
AB - Gram-negative bacteria have mechanisms through which they can colonize and
survive in different environments, such as the secretion systems types (1-6) that
have been widely studied and characterized. Nowadays, some authors have proposed
extracellular structures, such as the outer membrane vesicles (OMVs), to be
considered as an additional and independent secretion system. The OMVs are
spherical particles of 50-250 nm in diameter; they originate in the outer
membrane, and therefore they have a very similar composition to the latter. These
particles can transport an important variety of biomolecules: enzymes, toxins,
antigenic determinants and even nucleic acids. Thus, it is of great interest to
collect data describing the advantages of the transport of biomolecules through
the OMVs and, thus, determine their role as a potential secretion system.
PMID- 28421664
TI - Intermediate-term and long-term outcome of piggyback drainage: connecting
glaucoma drainage device to a device in-situ for improved intraocular pressure
control.
AB - IMPORTANCE: This study provides results of a treatment option for patients with
failed primary glaucoma drainage device. BACKGROUND: The study aimed to describe
and evaluate the long-term intraocular pressure control and complications of a
new technique joining a second glaucoma drainage device directly to an existing
glaucoma drainage device termed 'piggyback drainage'. DESIGN: This is a
retrospective, interventional cohort study. PARTICIPANTS: Eighteen eyes of 17
patients who underwent piggyback drainage between 2004 and 2013 inclusive have
been studied. All patients had prior glaucoma drainage device with uncontrolled
intraocular pressure. METHODS: The piggyback technique involved suturing a
Baerveldt (250 or 350 mm) or Molteno3 glaucoma drainage device to an unused
scleral quadrant and connecting the silicone tube to the primary plate bleb. MAIN
OUTCOME MEASURES: Failure of intraocular pressure control defined as an
intraocular pressure greater than 21 mmHg on maximal therapy on two separate
occasions or further intervention to control intraocular pressure. RESULTS: The
intraocular pressure was controlled in seven eyes (39%) at last follow-up with a
mean follow-up time of 74.2 months. The mean preoperative intraocular pressure
was 27.1 mmHg (95% confidence interval 23.8-30.3) compared with 18.4 mmHg (95%
confidence interval 13.9-22.8) at last follow-up. The mean time to failure was
57.1 months (95% confidence interval 32.2-82), and the mean time to further
surgery was 72.3 months (95% confidence interval 49.9-94.7). Lower preoperative
intraocular pressure was associated with longer duration of intraocular pressure
control (P = 0.048). If the intraocular pressure was controlled over 2 years, it
continued to be controlled over the long term. Two eyes (11%) experienced corneal
decompensation. CONCLUSIONS: Piggyback drainage represents a viable surgical
alternative for the treatment of patients with severe glaucoma with failing
primary glaucoma drainage device, particularly in those at high risk of corneal
decompensation.
PMID- 28421663
TI - Cloning and plant-based production of antibody MC10E7 for a lateral flow
immunoassay to detect [4-arginine]microcystin in freshwater.
AB - Antibody MC10E7 is one of a small number of monoclonal antibodies that bind
specifically to [Arg4]-microcystins, and it can be used to survey natural water
sources and food samples for algal toxin contamination. However, the development
of sensitive immunoassays in different test formats, particularly user-friendly
tests for on-site analysis, requires a sensitive but also cost-effective
antibody. The original version of MC10E7 was derived from a murine hybridoma, but
we determined the sequence of the variable regions using the peptide mass
assisted cloning strategy and expressed a scFv (single-chain variable fragment)
format of this antibody in yeast and a chimeric full-size version in leaves of
Nicotiana tabacum and Nicotiana benthamiana to facilitate inexpensive and
scalable production. The specific antigen-binding activity of the purified
antibody was verified by surface plasmon resonance spectroscopy and ELISA,
confirming the same binding specificity as its hybridoma-derived counterpart. The
plant-derived antibody was used to design a lateral flow immunoassay (dipstick)
for the sensitive detection of [Arg4]-microcystins at concentrations of 100-300
ng/L in freshwater samples collected at different sites. Plant-based production
will likely reduce the cost of the antibody, currently the most expensive
component of the dipstick immunoassay, and will allow the development of further
antibody-based analytical devices and water purification adsorbents for the
efficient removal of toxic contaminants.
PMID- 28421665
TI - Evaluation of high-intensity focused ultrasound ablation for uterine fibroids: an
IDEAL prospective exploration study.
AB - OBJECTIVE: To evaluate the clinical outcomes of high-intensity focused ultrasound
(HIFU) and surgery in treating uterine fibroids, and prepare for a definitive
randomised trial. DESIGN: Prospective multicentre patient choice cohort study
(IDEAL Exploratory study) of HIFU, myomectomy or hysterectomy for treating
symptomatic uterine fibroids. SETTING: 20 Chinese hospitals. POPULATION OR
SAMPLE: 2411 Chinese women with symptomatic fibroids. METHODS: Prospective non
randomised cohort study with learning curve analysis (IDEAL Stage 2b Prospective
Exploration Study). MAIN OUTCOME MEASURES: Complications, hospital stay, return
to normal activities, and quality of life (measured with UFS-Qol and SF-36 at
baseline, 6 and 12 months), and need for further treatment. Quality-of-life
outcomes were adjusted using regression modelling. HIFU treatment quality was
evaluated using LC-CUSUM to identify operator learning curves. A health economic
analysis of costs was performed. RESULTS: 1353 women received HIFU, 472
hysterectomy and 586 myomectomy. HIFU patients were significantly younger (P <
0.001), slimmer (P < 0.001), better educated (P < 0.001), and wealthier (P =
0.002) than surgery patients. Both UFS and QoL improved more rapidly after HIFU
than after surgery (P = 0.002 and P = 0.001, respectively at 6 months), but
absolute differences were small. Major adverse events occurred in 3 (0.2%) of
HIFU and in 133 (12.6%) of surgical cases (P < 0.001). Median time for hospital
stay was 4 days (interquartile range, 0-5 days), 10 days (interquartile range, 8
12.5 days) and 8 days (interquartile range, 7-10 days). CONCLUSIONS: HIFU caused
substantially less morbidity than surgery, with similar longer-term QoL. Despite
group baseline differences and lack of blinding, these findings support the need
for a randomised controlled trial (RCT) of HIFU treatment for fibroids. The IDEAL
Exploratory design facilitated RCT protocol development. TWEETABLE ABSTRACT: HIFU
had much better short-term outcomes than surgery for fibroids in 2411-patient
Chinese IDEAL format study.
PMID- 28421666
TI - Genetic interplay between human longevity and metabolic pathways - a large-scale
eQTL study.
AB - Human longevity is a complex phenotype influenced by genetic and environmental
components. Unraveling the contribution of genetic vs. nongenetic factors to
longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing
based expression quantitative trait loci study (eQTL) with subsequent
heritability analysis. The investigation was performed on blood samples from 244
individuals from Germany and Denmark, representing various age groups including
long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed
for the first time that human longevity is associated with a depletion of
metabolic pathways in a genotype-dependent and independent manner. Further
analyses indicated that 20% of the differentially expressed genes are influenced
by genetic variants in cis. The subsequent study of twins showed that the
transcriptional activity of a third of the differentially regulated genes is
heritable. These findings suggest that longevity-associated biological processes
such as altered metabolism are, to a certain extent, also the driving force of
longevity rather than just a consequence of old age.
PMID- 28421668
TI - Effects of Stoichiometry on the H2 -Storage Properties of Mg(NH2 )2 -LiH-LiBH4
Tri-Component Systems.
AB - The hydrogen desorption pathways and storage properties of 2 Mg(NH2 )2 -3 LiH
xLiBH4 samples (x=0, 1, 2, and 4) were investigated systematically by a
combination of pressure composition isotherm (PCI), differential scanning
calorimetric (DSC), and volumetric release methods. Experimental results showed
that the desorption peak temperatures of 2 Mg(NH2 )2 -3 LiH-xLiBH4 samples were
approximately 10-15 degrees C lower than that of 2 Mg(NH2 )2 -3 LiH. The 2
Mg(NH2 )2 -3 LiH-4 LiBH4 composite in particular began to release hydrogen at 90
degrees C, thereby exhibiting superior dehydrogenation performance. All of the
LiBH4 -doped samples could be fully dehydrogenated and re-hydrogenated at a
temperature of 143 degrees C. The high hydrogen pressure region (above 50 bar)
of PCI curves for the LiBH4 -doped samples rose as the amount of LiBH4 increased.
LiBH4 changed the desorption pathway of the 2 Mg(NH2 )2 -3 LiH sample under a
hydrogen pressure of 50 bar, thereby resulting in the formation of MgNH and
molten [LiNH2 -2 LiBH4 ]. That is different from the dehydrogenation pathway of 2
Mg(NH2 )2 -3 LiH sample without LiBH4 , which formed Li2 Mg2 N3 H3 and LiNH2 , as
reported previously. In addition, the results of DSC analyses showed that the
doped samples exhibited two independent endothermic events, which might be
related to two different desorption pathways.
PMID- 28421667
TI - Serum levels of Wisteria floribunda agglutinin-positive Mac-2 binding protein
reflect the severity of chronic pancreatitis.
AB - OBJECTIVES: To evaluate the utility of serum Wisteria floribunda agglutinin
positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic
pancreatitis (CP). METHODS: We measured the serum WFA+ -M2BP level of 74 patients
with CP who had undergone endoscopic retrograde cholangiopancreatography and 30
normal controls (NC) using a glycan sugar chain-based immunoassay and
investigated the relationship between serum WFA+ -M2BP levels and the Cambridge
classification of CP. RESULTS: Serum WFA+ -M2BP level was significantly higher in
patients with CP than in NC (0.64 +/- 0.28 vs 0.34 +/- 0.25, P < 0.001). The
levels (expressed as cut-off index) of WFA+ -M2BP for the classification of mild,
moderate and marked CP were 0.44, 0.63 and 0.87, respectively. Thus, serum WFA+
M2BP levels increased with increasing CP severity. With a cut-off value of 0.34,
0.59 and 0.61, the area under the receiver operating characteristic curve,
sensitivity and specificity were 0.829, 91.9% and 63.3% for mild CP; 0.891, 81.8%
and 85.0% for moderate CP; and 0.888, 92.0% and 74.7% for marked CP,
respectively. Multivariate analysis revealed that elevated serum WFA+ -M2BP was
independently associated with moderate and marked CP, respectively. CONCLUSION:
Serum WFA+ -M2BP level is a useful marker for grading CP severity.
PMID- 28421669
TI - Misfortune may be a blessing in disguise: Fairness perception and emotion
modulate decision making.
AB - Fairness perception and equality during social interactions frequently elicit
affective arousal and affect decision making. By integrating the dictator game
and a probabilistic gambling task, this study aimed to investigate the effects of
a negative experience induced by perceived unfairness on decision making using
behavioral, model fitting, and electrophysiological approaches. Participants were
randomly assigned to the neutral, harsh, or kind groups, which consisted of
various asset allocation scenarios to induce different levels of perceived
unfairness. The monetary gain was subsequently considered the initial asset in a
negatively rewarded, probabilistic gambling task in which the participants were
instructed to maintain as much asset as possible. Our behavioral results
indicated that the participants in the harsh group exhibited increased levels of
negative emotions but retained greater total game scores than the participants in
the other two groups. Parameter estimation of a reinforcement learning model
using a Bayesian approach indicated that these participants were more loss
aversive and consistent in decision making. Data from simultaneous ERP recordings
further demonstrated that these participants exhibited larger feedback-related
negativity to unexpected outcomes in the gambling task, which suggests enhanced
reward sensitivity and signaling of reward prediction error. Collectively, our
study suggests that a negative experience may be an advantage in the modulation
of reward-based decision making.
PMID- 28421670
TI - An epidemic of allergic contact dermatitis caused by a new allergen,
caprylhydroxamic acid, in moisturizers.
AB - BACKGROUND: In 2016, dermatologists in Finland suspected contact allergy in
several patients using moisturizers under the trade name Apobase(r). Following a
formulation change, PhenostatTM, which is a mixture of phenoxyethanol,
caprylhydroxamic acid, and methylpropanediol, was used as a preservative in
Apobase(r) moisturizers in Finland. OBJECTIVES: To confirm the suspected contact
allergy to Apobase(r) cream, oily cream, and/or lotion, and to identify the
specific contact allergen and define its optimal patch test concentration.
METHODS: Thirty-nine patients with suspected contact allergy to Apobase(r) creams
or lotion were patch tested in four Finnish dermatological clinics. The patch
tests included old and new Apobase(r) formulas and their preservative agents:
phenoxyethanol, methylpropanediol, and dilution series of PhenostatTM and
caprylhydroxamic acid or its potassium salt. RESULTS: The patch tests showed
positive reactions to the new Apobase(r) formulas, PhenostatTM, and
caprylhydroxamic acid or its potassium salt, but not to the old Apobase(r)
formulas, methylpropanediol, or phenoxyethanol. CONCLUSIONS: We found a new
contact allergen, caprylhydroxyamic acid, which caused an epidemic of allergic
contact dermatitis in patients using moisturizers containing this preservative.
Whether the sensitizing capacity of caprylhydroxamic acid depends on the other
chemicals used in Apobase(r) moisturizers needs further investigation.
PMID- 28421671
TI - Controlled Growth of CH3 NH3 PbI3 Using a Dynamically Dispensed Spin-Coating
Method: Improving Efficiency with a Reproducible PbI2 Blocking Layer.
AB - It is commonly believed that excess PbI2 has beneficial effects for perovskite
solar cells owing to the modification of charge-transport behavior at interfaces,
by surface passivation and by blocking electron-hole recombination. Here, we
introduce a dynamically dispensed spin-coating technique in a two-step deposition
to form a perovskite layer with controllable quantities of crystalline PbI2 .
Using this technique, the concentration of CH3 NH3 I solution is kept constant at
the reaction interface, ensuring smooth growth of films. By changing the spinning
rate during the reaction, the PbI2 conversion ratio and perovskite cuboid size
can be optimized, resulting in a power conversion efficiency improvement over
control devices. This dynamically dispensed technique represents a repeatable
method for compositional control in perovskite solar cells and improves our
understanding of how a PbI2 blocking layer improves the performance of perovskite
solar cells.
PMID- 28421672
TI - A Transplant-Specific Quality Initiative-Introducing TransQIP: A Joint Effort of
the ASTS and ACS.
AB - In an attempt to improve surgical quality in the field of transplantation, the
American College of Surgeons (ACS) and American Society of Transplant Surgeons
have initiated a national quality improvement program in transplantation. This
transplant-specific quality improvement program, called TransQIP, has been built
from the ground up by transplant surgeons and captures detailed information on
donor and recipient factors as well as transplant-specific outcomes. It is built
upon the existing ACS/National Surgical Quality Improvement Program
infrastructure and is designed to capture 100% of liver and kidney transplants
performed at participating sites. TransQIP has completed its alpha pilot and will
embark upon its beta phase at approximately 30 centers in the spring of 2017.
Going forward, we anticipate TransQIP will help satisfy Centers for Medicare and
Medicaid Services requirements for a quality improvement program, surgeon
requirements for maintenance of certification, and qualify as a clinical practice
improvement activity under the Merit-Based Incentive Payment System. Most
importantly, we believe TransQIP will provide insight into surgical outcomes in
transplantation that will allow the field to provide better care to our patients.
PMID- 28421674
TI - Retraction statement: Dynamic complex formation between HD-GYP, GGDEF and PilZ
domain proteins regulates motility in Xanthomonas campestris.
AB - : The following article from Molecular Microbiology (2012) 86(3), 557-567,
'Dynamic complex formation between HD-GYP, GGDEF and PilZ domain proteins
regulates motility in Xanthomonas campestris' by Robert P. Ryan, Yvonne McCarthy,
Patrick A. Kiely, Rosemary O'Connor, Chuck S. Farah, Judith P. Armitage and J.
Maxwell Dow published online in Wiley Online Library (wileyonlinelibrary.com),
has been retracted by agreement between the authors, the journal Editor-in-Chief,
John D Helmann, and John Wiley & Sons Ltd. Since publication of the above
article, it has been brought to our attention that there are several image
duplications across Figures 3, 5 and 6 including duplication with another article
in PNAS: 'Cell-cell signal-dependent dynamic interactions between HD-GYP and
GGDEF domain proteins mediate virulence in Xanthomonas campestris', by Robert P.
Ryan, Yvonne McCarthy, Maxuel Andrade, Chuck S. Farah, Judith P. Armitage, and J.
Maxwell Dow; PNAS (2010) 107(13), 5989-5994. The authors apologise for the errors
that arose due to poor labelling of the electronic images used in the
construction of the figures and for not spotting the duplication during review,
and, with agreement of all parties, the decision has been made to retract this
article. We apologise for any inconvenience the publication of this work may have
caused our readers. REFERENCES: Ryan, R.P., McCarthy, Y., Andrade, M., Farah,
C.S., Armitage, J.P., and Dow, J.M. (2010) Cell-cell signal-dependent dynamic
interactions between HD-GYP and GGDEF domain proteins mediate virulence in
Xanthomonas campestris. PNAS 107: 5989-5994. DOI: 10.1073/pnas.0912839107. Ryan,
R.P., McCarthy, Y., Kiely, P.A., O'connor, R., Farah, C.S., Armitage, J.P., and
Dow, J.M. (2012) Dynamic complex formation between HD-GYP, GGDEF and PilZ domain
proteins regulates motility in Xanthomonas campestris. Mol Microbiol 86: 557-567.
DOI: 10.1111/mmi.12000.
PMID- 28421673
TI - Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain
energy metabolism in mice.
AB - AIMS: The receptor tyrosine kinase ErbB4 is present throughout the primate brain
and has a distinct functional profile. In this study, we investigate the
potential role of endothelial ErbB4 receptor signaling in the brain. RESULTS:
Here, we show that the endothelial cell-specific deletion of ErbB4 induces
decreased exploratory behavior in adult mice. However, the water maze task for
spatial memory and the memory reconsolidation test reveal no changes;
additionally, we observe no impairment in CaMKII phosphorylation in
Cdh5Cre;ErbB4f/f mice, which indicates that the endothelial ErbB4 deficit leads
to decreased exploratory activity rather than direct memory deficits.
Furthermore, decreased brain metabolism, which was measured using micro-positron
emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the
immunoblot data demonstrate the downregulation of brain Glut1, phospho-ULK1
(Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice.
Collectively, our findings suggest that endothelial ErbB4 plays a critical role
in regulating brain function, at least in part, through maintaining normal brain
energy homeostasis. CONCLUSIONS: Targeting ErbB4 or the modulation of endothelial
ErbB4 signaling may represent a rational pharmacological approach to treat
neurological disorders.
PMID- 28421675
TI - Proteomic composition of the acrostyle: Novel approaches to identify cuticular
proteins involved in virus-insect interactions.
AB - The acrostyle is a distinct anatomical region present on the cuticle at the inner
face of the common food/salivary canal at the tip of aphid maxillary stylets.
This conserved structure is of particular interest as it harbors the protein
receptors of at least 1 plant virus, Cauliflower mosaic virus, and presumably has
other roles in plant-insect interactions. Previously we reported immunolabeling
of a highly conserved motif of cuticular proteins from the CPR family (named for
the presence of a Rebers and Riddiford consensus) within the acrostyle. Here we
report the development of novel tools to further study the proteomic composition
of this region and to identify proteins involved in insect-virus interactions.
Using a series of antibodies against cuticular proteins from the RR-2 subfamily,
we identified additional peptides present within the acrostyle. Our results
demonstrated that the acrostyle is a complex structure containing multiple
domains of cuticular proteins accessible for interaction. In addition, an array
of overlapping peptides, which covers the diversity of the majority of the RR-2
subfamily, was developed as a generic tool to characterize cuticular
protein/pathogen interactions. Upon probing this array with Cucumber mosaic virus
particles, consensus peptide sequences from hybridizing peptides were identified.
Use of these novel tools has extended our knowledge of the proteomic composition
of insect maxillary stylets and identified sequences that could be involved in
virus binding, thus contributing to further elucidation of the various properties
and functions of the acrostyle.
PMID- 28421678
TI - Synergetic Effect of Chloride Doping and CH3 NH3 PbCl3 on CH3 NH3 PbI3-x Clx
Perovskite-Based Solar Cells.
AB - The chloride-doped CH3 NH3 PbI3-x Clx perovskite has attracted great attention
owing to clear performance enhancement by using a Cl additive and by the
controversial arguments on Cl function and the mechanism behind it. Herein, a
series of CH3 NH3 PbI3-x Clx perovskites with various Cl content was prepared
through a gas/solid reaction between CH3 NH2 gas and HPbI3-x Clx (x=0-1). The
small amount of Cl doping in CH3 NH3 PbI3-x Clx (x=0.05) could lead to band gap
broadening and significantly increase the perovskite grain size, and the phase
pure CH3 NH3 PbI2.95 Cl0.05 perovskites exhibited up to 17.44 % efficiency. For
Cl contents higher than 0.1 (x>0.1), CH3 NH3 PbCl3 formed and coexisted with CH3
NH3 PbI3-x Clx , and CH3 NH3 PbCl3 could help to improve the thermal stability of
CH3 NH3 PbI3-x Clx . However, the excessive co-existing wide-band-gap CH3 NH3
PbCl3 perovskites would inhibit the electron transfer and lead to a deterioration
of photovoltaic performance.
PMID- 28421677
TI - Mindfulness and its efficacy for psychological and biological responses in women
with breast cancer.
AB - Many breast cancer survivors have to deal with a variety of psychological and
physiological sequelae including impaired immune responses. The primary purpose
of this randomized controlled trial was to determine the efficacy of a
mindfulness-based stress reduction (MBSR) intervention for mood disorders in
women with breast cancer. Secondary outcomes were symptom experience, health
status, coping capacity, mindfulness, posttraumatic growth, and immune status.
This RTC assigned 166 women with breast cancer to one of three groups: MBSR (8
weekly group sessions of MBSR), active controls (self-instructing MBSR) and non
MBSR. The primary outcome measure was the Hospital Anxiety and Depression Scale.
Secondary outcome measures were: Memorial Symptom Assessment Scale, SF-36, Sense
of Coherence, Five Facets of Mindfulness Questionnaire, and Posttraumatic Growth
Index. Blood samples were analyzed using flow cytometry for NK-cell activity
(FANKIA) and lymphocyte phenotyping; concentrations of cytokines were determined
in sera using commercial high sensitivity IL-6 and IL-8 ELISA (enzyme-linked
immunosorbent assay) kits. Results provide evidence for beneficial effects of
MBSR on psychological and biological responses. Women in the MBSR group
experienced significant improvements in depression scores, with a mean pre-MBSR
HAD-score of 4.3 and post-MBSR score of 3.3 (P = 0.001), and compared to non-MBSR
(P = 0.015). Significant improvements on scores for distress, symptom burden, and
mental health were also observed. Furthermore, MBSR facilitated coping capacity
as well as mindfulness and posttraumatic growth. Significant benefits in immune
response within the MBSR group and between groups were observed. MBSR have
potential for alleviating depression, symptom experience, and for enhancing
coping capacity, mindfulness and posttraumatic growth, which may improve breast
cancer survivorship. MBSR also led to beneficial effect on immune function; the
clinical implications of this finding merit further research.
PMID- 28421679
TI - Thomas Starzl-Visionary and xenotransplantation pioneer: Commentary from the
International Xenotransplant Association Vanguard Committee.
PMID- 28421680
TI - Thomas E. Starzl, MD, PhD, 1926-2017.
PMID- 28421681
TI - Early clinical xenotransplantation experiences-An interview with Thomas E.
Starzl, MD, PhD.
AB - Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of
organ transplantation. He was also a pioneer in the field of xenotransplantation.
In 1964, he carried out baboon kidney transplants in six patients with terminal
renal disease for whom no living or deceased donor became available; graft
survival was for 19-60 days, the grafts being lost largely through continuous
complement activation. Between 1966 and 1974, he carried out one ex vivo liver
perfusion and three orthotopic liver transplants using chimpanzees as sources of
organs; graft survival was for <14 days. In 1992 and 1993, his team carried out
baboon liver transplantation in two patients with cirrhosis from hepatitis B
infection; graft survival was for 70 and 26 days, respectively. This early
clinical experience is briefly discussed. Toward the end of his life, Dr Starzl
was somewhat disillusioned by what he considered excessive regulation of medical
research in the United States and believed that new advances were now likely to
take place in countries such as China, where the regulatory framework is less
developed.
PMID- 28421682
TI - Predicting abstinence from methamphetamine use after residential rehabilitation:
Findings from the Methamphetamine Treatment Evaluation Study.
AB - INTRODUCTION AND AIMS: We previously found that residential rehabilitation
increased continuous abstinence from methamphetamine use 1 year after treatment.
We examine what client and treatment characteristics predict this outcome. DESIGN
AND METHODS: Participants (n = 176) were dependent on methamphetamine and
entering residential rehabilitation for methamphetamine use. Simultaneous
logistic regression was used to identify independent predictors of continuous
abstinence from methamphetamine use at 1 year follow-up. Measures included
demographics, drug use, psychiatric comorbidity (Diagnostic and Statistical
Manual of Mental Disorders, major depression, social phobia, panic disorder,
schizophrenia, mania and conduct disorder), symptoms of psychosis and hostility,
readiness to change, motivations for treatment and treatment characteristics
(duration, rapport, group and individual counselling). RESULTS: Participants
stayed in treatment for a median of 8 weeks; 23% remained abstinent at 1 year.
The only independent predictors of abstinence were more weeks in treatment
[adjusted odds ratio (AOR) 1.2, P < 0.001], better rapport with treatment
providers (AOR 2.4, P = 0.049) and receipt of individual counselling (AOR 3.7, P
= 0.013), whereas injecting methamphetamine predicted not achieving abstinence
(AOR = 0.25, P = 0.002). Individual counselling and good rapport increased
abstinence to 45%; for injectors, longer stays in treatment (13+ weeks) were
additionally needed to produce similar abstinence rates (43%). DISCUSSIONS AND
CONCLUSIONS: Abstinence from methamphetamine use following residential
rehabilitation could be significantly increased by providing individual
counselling, maintaining good rapport with clients and ensuring longer stays for
people who inject the drug. [McKetin R, Kothe A, Baker AL, Lee NK, Ross J, Lubman
DI. Predicting abstinence from methamphetamine use after residential
rehabilitation: Findings from the Methamphetamine Treatment Evaluation Study.
Drug Alcohol Rev 2018;37:70-78].
PMID- 28421683
TI - A numerical investigation on the effect of RF coil feed variability on global and
local electromagnetic field exposure in human body models at 64 MHz.
AB - PURPOSE: This study aims to investigate how the positions of the feeding sources
of the transmit radiofrequency (RF) coil, field orientation direction with
respect to the patient, and patient dimensions affect the global and local
electromagnetic exposure in human body models. METHODS: Three RF coil models were
implemented, namely a specific two-source (S2) feed and two multisource feed
configurations: generic 32-source (G32) and hybrid 16-source (H16). Thirty-two
feeding conditions were studied for the S2, whereas two were studied for the G32
and H16. The study was performed using five human body models. Additionally, for
two of the body models, the case of a partially implanted lead was evaluated.
RESULTS: The results showed an overall variation due to coil feeding conditions
of the whole-body specific absorption rate (SAR) of less than 20%, but deviations
up to 98% of the magnitude of the electric field tangential to a possible lead
path. For the analysis with the partially implanted lead, a variation of local
SAR at the tip of the lead of up to 60% was observed with respect to feed
position and field orientation direction. CONCLUSION: The results of this study
suggest that specific information about feed position and field orientation
direction must be considered for an accurate evaluation of patient exposure. Magn
Reson Med 79:1135-1144, 2018. (c) 2017 International Society for Magnetic
Resonance in Medicine.
PMID- 28421684
TI - Navigating the Rolling Hills of Justice: Mental Disabilities, Employment and the
Evolving Jurisprudence of the Americans with Disabilities Act.
AB - Mental illness and disability affect millions of individuals yearly in the U.S.
The most important legislation protecting the mentally disabled in the workplace
in the U.S. over the last half century has been the Americans with Disabilities
Act (ADA) and its associated legislation and guidance. Although the employee
should first request reasonable accommodation with the employer, evaluation by a
mental health professional is one of the initial steps for individuals who report
significant psychiatric symptoms that are impairing their functioning at work in
the U.S.. Important regulations and laws in the United States that are essential
knowledge to performing thorough mental disability evaluations include the ADA
and Americans with Disabilities Act Amendments Act of 2008 (ADAAA), Social
Security Disability, Workers' Compensation, and private disability insurance.
These laws differ in applicability and in their definitions of disability. Social
Security Disability is applicable to workers who have long-term impairments
regardless of whether the disability arose on or off the job, while Worker's
Compensation is specific to persons with work-related illness and injuries that
occur on the job (Reno, Williams, & Sengupta, ). The Social Security definition
of a disabled person is a person who is not "able to engage in any substantial
gainful activity because of a medically-determinable physical or mental
impairment(s): that is expected to result in death, or that has lasted or is
expected to last for a continuous period of at least 12 months" (Social Security
Red Book, ). However, the Workers' Compensation definition of what
illnesses/injuries are compensated, the level of benefits and who provides the
insurance are state-specific. Due to these differences in definition of
disability, it is essential for the mental health professional performing a
mental disability evaluation to clarify with the referral source or referring
agency which legislation and laws they feel are directly relevant to the specific
situation before starting the evaluation. While the ADA and ADA Amendments Act of
2008 have had the greatest impact on the improvement of conditions for mentally
disabled individuals in employment over the last 25 years, they have also been
the most challenging by far for mental health experts to understand and apply
(Cook, ). Interestingly, the ADA has had a much quicker effect on improving
access to services for the medically disabled as compared with the mentally
disabled in the U.S. (Ullman, Johnsen, Moss, & Burris, ). This article reviews
the history and status of current ADA- and ADAAA-related law and employment as
well as Canadian disability law and global progress towards universal disability
legislation as evidenced by the 2006 Convention on the Rights of Persons with
Disabilities. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421685
TI - The Reach and Limitation of the ADA and its Integration Mandate: Implications for
the Successful Reentry of Individuals with Mental Disabilities in a Correctional
Population.
AB - This article argues that the ADA and its integration mandate, informed by
international standards, should extend to incarcerated individuals with mental
disabilities who reenter society, as they are at highly elevated risk for
unnecessary segregation in institutions such as homeless shelters or hospitals or
through reincarceration. An understanding of the precise services needed to
prevent these strongly related but distinct variants of institutionalization
requires a robust and continuing research agenda. In discussing the breadth of
the ADA, we explore its history, interpretations of its application in a variety
of contexts with respect to vulnerable populations and integration, and
enforcement. We also turn to international approaches to integration mandates as
they apply to reentry. By interpreting the domestic and international principles
that create the context for integration we hope to have provided a resource for
future application of the ADA integration in the context of prisoner reentry.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421686
TI - International Perspectives on Mental Disability and the Law: Introduction to this
Issue.
PMID- 28421687
TI - Contemporary Data and Trends in the Economic Costs of Mental Disabilities.
AB - This article addresses the economic effects of mental disabilities by analyzing
contemporary data in the context of micro- and macroeconomic thought and relevant
statistical literature. Within the parameters of these conceptual and statistical
reference points, the authors seek to discern current trends in the direct,
indirect, and opportunity costs posed by mental disabilities, not only to the
individuals who suffer from them, but also to their families, to employers, and
to society as a whole. The authors also discuss uncertainties that inhere in
available data concerning both the prevalence of these conditions and the related
costs of treatment, as well as the complexity of drawing correlations among
variables with respect to these costs and the difficulty of identifying a
meaningful measure of the economic consequences that attend mental disabilities.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421688
TI - Typical medullary breast carcinoma: Clinical outcomes and treatment results.
PMID- 28421689
TI - On-resin N-formylation of peptides: a head-to-head comparison of reagents in
solid-phase synthesis of ligands for formyl peptide receptors.
AB - 4-Nitrophenyl formate was found to be the most convenient reagent in solid-phase
formylation of peptides with a high formylation degree within 20 min to 3 h
depending on reaction temperature and length of peptide.
PMID- 28421690
TI - Alcohol use of immigrant youths in The Netherlands: The roles of parents and
peers across different ethnic backgrounds.
AB - INTRODUCTION AND AIMS: The aims of this study were to examine the roles of
parental permissiveness toward alcohol use and affiliation with alcohol-using
peers in alcohol use in youths from various ethnic backgrounds, and whether the
role of peers was moderated by parental permissiveness. In addition, differences
in these associations between native Dutch and non-Western immigrant youths were
examined. DESIGN AND METHODS: Cross-sectional data of 578 youths with Surinamese,
Moroccan, Turkish, Antillean and Asian backgrounds and 81 native Dutch were used,
all aged 15-24. Alcohol use, affiliation with alcohol-using peers and parental
permissiveness were measured using self-report questionnaires. Regression models
controlled for age, religiousness, education level and parental alcohol use.
Because of very low levels of alcohol use, data from Turkish and Moroccan
immigrants were aggregated, and logistic regression analyses were performed.
RESULTS: Parental permissiveness and affiliation with alcohol-using peers were
positively related to level of alcohol use in youths with Surinamese, Antillean
and Asian backgrounds and played an equally strong role in native Dutch youths
with one exception. In Surinamese youths, parental permissiveness was more
strongly related to alcohol use than in native Dutch youths. In youths with a
Turkish/Moroccan background, parental permissiveness and affiliation with alcohol
using peers were strongly associated with any (versus no) alcohol use. Only
parental permissiveness was, equally strong, associated with any alcohol use in
native Dutch youths. DISCUSSION AND CONCLUSIONS: Irrespective of ethnic
background and differences in level of alcohol use, parental permissiveness and
affiliation with alcohol-using peers are related to youth alcohol use. [Creemers
HE, Spanakis P, Delforterie MJ, Huizink AC. Alcohol use of immigrant youths in
The Netherlands: The roles of parents and peers across different ethnic
backgrounds.
PMID- 28421691
TI - The impact of maternal employment on children's adiposity: Evidence from China's
labor policy reform.
AB - BACKGROUND: China has experienced a rapid growth in childhood adiposity in recent
years. Although a large number of studies examine the effect of maternal
employment on children's adiposity in developed countries, only a few studies
investigate the issue in developing countries. Moreover, existing studies tend to
suffer from a potential endogeneity issue. AIMS: We provide new evidence on the
causal effect of maternal employment on children's adiposity in China. MATERIALS
AND METHODS: We employ a difference-in-difference strategy that takes advantage
of China's 1995 legislative change to labor regulations, which reduced the number
of workdays from 6 to 5 days per week. Using longitudinal data from the China
Health and Nutrition Survey (CHNS), we compare children whose mothers are wage
earning employees to those whose mothers are self-employed because the reform
only affected the former. RESULTS: Although maternal employment and childhood
obesity in China exhibits the same positive association as in the United States,
our difference-in-difference estimates present a different picture. We find that
a reduction in the maternal labor supply led to children's weight gain. Further
investigation reveals that the effect was stronger among children who were male,
younger, in urban areas, and from households with low socioeconomic status.
DISCUSSION: Our evidence suggests that a change in maternal behaviors was likely
responsible for children's weight gain. In particular, a greater proportion of
treatment group mothers cooked and also devoted more time to cooking after the
reform, which led to an increased caloric intake by their children. Such weight
gain was beneficial for children who were previously underweight but harmful to
those who became overweight. CONCLUSION: The finding implies that additional
maternal time at home likely has a different effect in China compared to the
United States.
PMID- 28421695
TI - Evaluation of an interview skills training package for adolescents with speech,
language and communication needs.
AB - BACKGROUND & AIMS: We evaluated a structured intervention programme aimed at
preparing adolescents with developmental language disorders for job interviews.
Our primary outcome measures included change in ratings of verbal and non-verbal
social communication behaviours evident during mock interviews. METHODS &
PROCEDURES: In study 1, 12 participants, aged 17-19 years, from a specialist
sixth-form college completed the intervention and two mock interviews, one pre-
and one post-intervention. In study 2, 34 participants, aged 17-19 years,
completed a modified intervention programme and three mock interviews, one at
baseline (included to control for possible practise effects), one pre- and one
post-intervention. In both studies, interviews were video recorded and social
communication behaviours were coded by independent assessors blind to interview
time, participant diagnosis and therapy content. A repeated-measures design was
employed to measure change in communication behaviours. OUTCOMES & RESULTS: In
study 1, a significant increase in the number of 'positive' verbal and non-verbal
social communication behaviours was observed from pre- to post-intervention.
However, there was no significant change in the number of 'negative' behaviours
(i.e., fidgeting, irrelevant remarks). In study 2, there were no significant
changes in verbal behaviours, but significant group differences (though wide
individual variation) in both positive and negative non-verbal social
communication behaviours. CONCLUSIONS & IMPLICATIONS: Our findings suggest that
training specific social communication skills that are important for interview
success, and consistently reinforcing those behaviours during therapy practice,
can increase the use of those skills in an interview setting, though in this
heterogeneous population there was considerable variation in therapy outcome. The
skills of the interviewer were identified as a potential source of variation in
outcome, and a target for future research and practice.
PMID- 28421694
TI - Molecular engineering and plant expression of an immunoglobulin heavy chain
scaffold for delivery of a dengue vaccine candidate.
AB - In order to enhance vaccine uptake by the immune cells in vivo, molecular
engineering approach was employed to construct a polymeric immunoglobulin G
scaffold (PIGS) that incorporates multiple copies of an antigen and targets the
Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens
were tested in the context of dengue infection, for which there is currently no
globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII)
of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco
plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII-PIGS were
fractionated by HPLC into low and high molecular weight forms, corresponding to
monomers, dimers and polymers. cEDIII-PIGS were shown to retain important Fc
receptor functions associated with immunoglobulins, including binding to C1q
component of the complement and the low affinity Fcgamma receptor II, as well as
to macrophage cells in vitro. These molecules were shown to be immunogenic in
mice, with or without an adjuvant, inducing a high level IgG antibody response
which showed a neutralizing potential against the dengue virus serotype 2. The
cEDIII-PIGS also induced a significant cellular immune response, IFN-gamma
production and polyfunctional T cells in both the CD4+ and CD8+ compartments.
This proof-of-principle study shows that the potent antibody Fc-mediated cellular
functions can be harnessed to improve vaccine design, underscoring the potential
of this technology to induce and modulate a broad-ranging immune response.
PMID- 28421696
TI - Assessing causality in drug policy analyses: How useful are the Bradford Hill
criteria in analysing take-home naloxone programs?
AB - The Bradford Hill criteria for assessing causality are useful in assembling
evidence, including within complex policy analyses. In this paper, we argue that
the implementation of take-home naloxone (THN) programs in Australia and
elsewhere reflects sensible, evidence-based public health policy, despite the
absence of randomised controlled trials. However, we also acknowledge that the
debate around expanding access to THN would benefit from a careful consideration
of causal inference and health policy impact of THN program implementation. Given
the continued debate around expanding access to THN, and the relatively recent
access to new data from implementation studies, two research groups independently
conducted Bradford Hill analyses in order to carefully consider causal inference
and health policy impact. Hill's criteria offer a useful analytical tool for
interpreting current evidence on THN programs and making decisions about the
(un)certainty of THN program safety and effectiveness.
PMID- 28421698
TI - Historical harvests reduce neighboring old-growth basal area across a forest
landscape.
AB - While advances in remote sensing have made stand, landscape, and regional
assessments of the direct impacts of disturbance on forests quite common, the
edge influence of timber harvesting on the structure of neighboring unharvested
forests has not been examined extensively. In this study, we examine the impact
of historical timber harvests on basal area patterns of neighboring old-growth
forests to assess the magnitude and scale of harvest edge influence in a forest
landscape of western Oregon, USA. We used lidar data and forest plot measurements
to construct 30-m resolution live tree basal area maps in lower and middle
elevation mature and old-growth forests. We assessed how edge influence on total,
upper canopy, and lower canopy basal area varied across this forest landscape as
a function of harvest characteristics (i.e., harvest size and age) and
topographic conditions in the unharvested area. Upper canopy, lower canopy, and
total basal area increased with distance from harvest edge and elevation. Forests
within 75 m of harvest edges (20% of unharvested forests) had 4% to 6% less live
tree basal area compared with forest interiors. An interaction between distance
from harvest edge and elevation indicated that elevation altered edge influence
in this landscape. We observed a positive edge influence at low elevations (<800
m) and a negative edge influence at moderate to high elevations (>800 m).
Surprisingly, we found no or weak effects of harvest age (13-60 yr) and harvest
area (0.2-110 ha) on surrounding unharvested forest basal area, implying that
edge influence was relatively insensitive to the scale of disturbance and multi
decadal recovery processes. Our study indicates that the edge influence of past
clearcutting on the structure of neighboring uncut old-growth forests is
widespread and persistent. These indirect and diffuse legacies of historical
timber harvests complicate forest management decision-making in old-growth forest
landscapes by broadening the traditional view of stand boundaries. Furthermore,
the consequences of forest harvesting may reach across ownership boundaries,
highlighting complex governance issues surrounding landscape management of old
growth forests.
PMID- 28421699
TI - Hepatic infarction from portal vein thrombosis: A fatal consequence of acute
pancreatitis.
PMID- 28421697
TI - Endothelium originated from colorectal cancer stem cells constitute cancer blood
vessels.
AB - Tumor growth depends on the formation of blood vessels that provide the supply of
nutrients and oxygen. Previous data have shown that glioblastoma stem cells are
able to give rise to vascular cells to constitute the functional vessels in tumor
tissues. However, which kinds of vascular cells are generated from glioblastoma
stem cells is largely debated. In addition, there is little evidence showing that
the stem cells from other kinds of tumors can produce vascular cells to
constitute the functional blood vessels in tumor tissues. Here we show that
cancer stem cells of human colorectal carcinomas (CoCSC) can give rise to
vascular endothelial cells and compose the vasculatures in cancer tissues. The
human-cell-specific nuclear antigen NuMA+ vascular endothelial cells were
detected in the blood vessels in xenografts derived from CoCSC. NuMA+ endothelial
cells incorporated into functional blood vessels. Our data indicate that the
cancer stem cells derived from human colorectal carcinomas have the capacity to
generate functional blood vessels and provide a new mechanism for tumor
vasculogenesis in carcinoma.
PMID- 28421700
TI - Growth characteristics and endocrine abnormalities in 22q11.2 deletion syndrome.
AB - 22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features
including endocrine abnormalities. We aimed to characterize growth patterns,
hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS.
Anthropometric and laboratory measurements were obtained from the charts of 48
individuals (males=28, 8.0+/-6.8 visits/participant) followed at a national
22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3+/-4.9 years and
age at last evaluation 11.2+/-7.2 years. Median height-SDS was negative at all
ages. Height-SDS at last visit was correlated to the midparental height-SDS
(r=0.52 P=0.002). Yet, participants did not reach their target height, with a
difference of 1.06+/-1.07 SD (P <0.0001). Height-SDS at last visit of
participants with a heart defect was lower compared to participants with a normal
heart (-1.5+/-1.4 vs. -0.6+/-0.8, P=0.036), with lower height-SDS in the subgroup
of participants with severe heart defects (-2.1+/-1.6, P=0.009). Mean IGF1-SDS
was low (-0.99+/-1.68) but was not correlated with height-SDS. Thirteen patients
(27%) had hypoparathyroidism: 10 presented during infancy and 3 during
adolescence. Five patients (10.4%, female=4) had thyroid abnormalities. In
conclusions, individuals with 22q11.2 DS have a distinct growth pattern
consisting of growth restriction at all ages, resulting in final adult height in
the low-normal range. Hypoparathyroidism is common and may present during the
neonatal period as well as later in life. Thyroid abnormalities may present
during childhood, adolescence, or adulthood.
PMID- 28421701
TI - Corrigendum to "Having a son or daughter with Down syndrome: Perspectives from
mothers and fathers. Am J Med Genet Part A 155:2335-2347."
PMID- 28421702
TI - De Novo Variants Associated With Developmental Disability: Exome sequencing data
findings implicate new genes as potential sources of de novo mutations.
PMID- 28421703
TI - Foremost Prenatal Physician, Scientist Tapped to Lead National Child Health
Agency: Diana Bianchi, MD, is focused on fostering more genomics research,
enabling greater data-sharing collaboration among agencies in new role at NICHD.
PMID- 28421706
TI - Generative Topographic Mapping of Conformational Space.
AB - Herein, Generative Topographic Mapping (GTM) was challenged to produce planar
projections of the high-dimensional conformational space of complex molecules
(the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity
to support property prediction models serves to objectively assess map quality
(in terms of regression statistics). The properties to predict were total, non
bonded and contact energies, surface area and fingerprint darkness. Map building
and selection was controlled by a previously introduced evolutionary strategy
allowed to choose the best-suited conformational descriptors, options including
classical terms and novel atom-centric autocorrellograms. The latter condensate
interatomic distance patterns into descriptors of rather low dimensionality, yet
precise enough to differentiate between close favorable contacts and atom
clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from
a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map
building and cross-validation of property regression models. The GTM build-up
challenge reached robust three-fold cross-validated determination coefficients of
Q2 =0.7...0.8, for all modeled properties. Mapping of the full 2 M conformer set
produced intuitive and information-rich property landscapes. Functional and
folding subspaces appear as well-separated zones, even though RMSD with respect
to the PDB structure was never used as a selection criterion of the maps.
PMID- 28421707
TI - Content analysis of the professional journal of the Royal College of Speech and
Language Therapists, III: 1966-2015-into the 21st century.
AB - BACKGROUND: Following content analyses of the first 30 years of the UK speech and
language therapy professional body's journal, this study was conducted to survey
the published work of the speech (and language) therapy profession over the last
50 years and trace key changes and themes. AIM: To understand better the
development of the UK speech and language therapy profession over the last 50
years. METHODS & PROCEDURES: All volumes of the professional journal of the Royal
College of Speech and Language Therapists published between 1966 and 2015
(British Journal of Communication Disorders, European Journal of Communication
Disorders and International Journal of Language and Communication Disorders) were
examined using content analysis. The content was compared with that of the same
journal as it appeared from 1935 to 1965. OUTCOMES & RESULTS: The journal has
shown a trend towards more multi-authored and international papers, and a
formalization of research methodologies. The volume of papers has increased
considerably. Topic areas have expanded, but retain many of the areas of study
found in earlier issues of the journal. CONCLUSIONS & IMPLICATIONS: The journal
and its articles reflect the growing complexity of conditions being researched by
speech and language therapists and their professional colleagues and give an
indication of the developing evidence base for intervention and the diverse
routes which speech and language therapy practice has taken over the last 50
years.
PMID- 28421708
TI - Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl-Alkyl Cross
Coupling.
AB - Vicinal stereocenters are found in many natural and unnatural compounds. Although
metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are
emerging as a powerful tool in organic synthesis, there have been virtually no
reports of processes that generate, much less control, vicinal stereocenters. In
this investigation, we establish that a chiral nickel catalyst can mediate doubly
stereoconvergent alkyl-alkyl cross-coupling, specifically, reactions of a racemic
pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of
stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.
PMID- 28421709
TI - Gene-environment interaction influences attachment-like style in mice.
AB - Attachment styles are established soon after birth and form the basis for a
healthy psychological life during adulthood. Here, we investigated whether
genetic background (i.e. isogenic strains: C57BL/6N and BALB/c) and parent-of
origin (i.e. reciprocal hybrids) epigenetic effects influence attachment-like
styles in mice. We discovered that a specific genetic and epigenetic assortment
exerts a role on the development of a secure or insecure attachment-like style.
In particular, when biological mothers raise their pups, the attachment-like
style is mainly secure, independently of the genetic background. However, when
foster mothers raise pups, the attachment-like style can be either secure or
insecure, depending on the particular genetic background, and this effect is
paternally transmitted. Finally, we observed that secure attachment-like in mice
leads to greater sociability during adulthood, while insecure attachment-like
leads to reduced sociability. Our study sheds light on gene-environment
interactions that shape the attachment-like style early in development and pave
the way for a healthy psychological life.
PMID- 28421710
TI - Synovial sarcoma metastatic to the parotid gland: A possible pitfall in salivary
gland fine needle aspiration cytology. Report of a case with immunocytochemical
and fluorescence in situ hybridization findings.
AB - We report one case of metastatic synovial sarcoma (SS) to the parotid gland in a
93-year-old male. The patient had undergone upper left pulmonary lobectomy with
mediastinal lymphadenectomy for SS of the lung 5 years before. The cytopathologic
presentation and the immunocytochemical findings on the FNA sample were
suggestive of a spindle cell myoepithelioma, while a SYT rearrangement was
identified by a FISH performed on a cytological smear of the lesion. The
diagnosis was further confirmed also by positive immunocytochemical expression of
TLE1 on a section from the obtained cell block. The cytologic and
immunophenotypic findings are shortly discussed in view of the reported
immunophenotypic inconsistency of SS and of its differential diagnosis with
spindle cell myoepithelioma of the salivary glands.The importance of the recently
described TLE1 staining and its close correlation to SYT rearrangement is briefly
discussed.
PMID- 28421712
TI - Gastric cancer with pituitary metastasis presenting as symptomatic secondary
adrenal insufficiency: A case report.
PMID- 28421711
TI - Vitamin D status of White pregnant women and infants at birth and 4 months in
North West England: A cohort study.
AB - The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and
their infants has not been investigated at northern latitudes in a developed
county. A 2-year observational cohort study was undertaken in the North West of
England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants
during pregnancy and 4 months postdelivery and to explore factors associated with
these levels. Nutritional and lifestyle questionnaires were completed and 25OHD
levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and
7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48%
and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have
significantly lower 25OHD than other skin types after controlling for time spent
outside and vitamin D intake. Twenty-four percent and 13% of infants had
insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed
infants have the highest level of insufficiency (67%) compared with formula-fed
infants (2%). Factors associated with infant serum 25OHD levels at 4 months
included breast feeding, supplementation, and time outside. WSW have a high
prevalence of insufficiency and deficiency during pregnancy which doubles 4
months after birth. Breast-fed infants of WSW are rarely considered at risk of
vitamin D insufficiency but have high rates compared with formula-fed infants.
This is the first study to show the finding that FST I WSW have significantly
lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and
time outside 14 (95%CI 7-21) nmol/L).
PMID- 28421713
TI - Identification, isolation, and synthesis of seven novel impurities of anti
diabetic drug Repaglinide.
AB - Seven unknown impurities in Repaglinide bulk drug batches at below 0.1% (ranging
from 0.05 to 0.10%) were detected by an ultra-performance liquid chromatographic
(UPLC) method. These impurities were isolated from the crude sample of
Repaglinide using preparative high performance liquid chromatography (prep-HPLC).
Based on liquid chromatography-electrospray ionization-mass spectrometry (LC
ESI/MS) study, the chemical structures of seven new impurities (8, 9, 10, 11, 13,
14, and 16) were presumed and characterized as 4-(cyanomethyl)-2-ethoxybenzoic
acid (8), 4-(cyanomethyl)-2-ethoxy-N-(3-methyl-1-(2-(piperidin-1
yl)phenyl)butyl)benzamide (9), 4-(2-amino-2-oxoethyl)-2-ethoxy-N-(3-methyl-1-(2
(piperidin-1-yl)phenyl)butyl) benzamide (10) and 2-(3-ethoxy-4-((3-methyl-1-(2
(piperidin-1-yl)phenyl)butyl) carbamoyl) phenyl) acetic acid (11) and 4
(cyanomethyl)-N-cyclohexyl-2-ethoxybenzamide (13), 2-(4-(cyclohexylcarbamoyl)-3
ethoxyphenyl) acetic acid (14) and N-cyclohexyl-4-(2-(cyclohexylamino)-2
oxoethyl)-2-ethoxybenzamide (16). The complete spectral analysis, proton nuclear
magnetic resonance (1 H NMR), 13 C NMR, MS, and infrared (IR) confirmed the
proposed chemical structures of impurities. Identification, structural
characterization, formation, and their synthesis was first reported in this
study. The impurity 11 was crystallized and structure was solved by single
crystal X-ray diffraction. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28421714
TI - Endometrial cells on Pap tests: ideal reporting is more complex than just finding
the right age.
AB - BACKGROUND: The age for reporting normal endometrial cells (EMCs) on Pap tests
was changed to >= 45 years in the latest Bethesda update (2014). This
recommendation is solely based on age with no consensus on optimal reporting
guidelines. METHODS: Pap tests with EMCs for women >=40 years were retrieved from
our Laboratory Information System (LIS). Patient age, last menstrual period (LMP)
and available follow-up histology were recorded. Follow-up diagnoses were
categorized as: no significant pathology, benign, hyperplasia +/- atypia, or
malignant. The Fisher's exact test was used to assess the association between
categorical variables, p < .05 (two-sided test) was considered significant.
RESULTS: Of the 352 cases with EMCs, 155 had surgical follow-up. They showed no
malignancy in the 89 women between 40-49 years, compared with five malignancies
in the 66 women 50+ years (p = .016). The number of cases with significant
pathology (hyperplasia and malignant) was 4 (40-49 years) vs. 11 (50+ years) (p =
0.029). The LMP was inconsistently provided (57%) and women identified as
postmenopausal on requisition comprised all the malignancies and half the
hyperplasias. CONCLUSION: Combined effort by pathologists and clinicians
necessitates determining the best standardized clinicopathologic guidelines to
report EMCs and appropriate follow-up. Increasing the required age to >=50 years
would provide more optimal patient management; however, there are other
considerations beyond age. Reporting EMCs in postmenopausal women is a reasonable
alternative requiring consistent and accurate recording of LMP. Improving
provided information for pathologists, determining reporting requirements for
EMCs and standardizing clinical follow-up should be a multidisciplinary effort.
Diagn. Cytopathol. 2017;45:587-591. (c) 2017 Wiley Periodicals, Inc.
PMID- 28421715
TI - Effect of water bath temperature on physiological parameters and subjective
sensation in older people.
AB - AIM: In Japan, the incidence of water bathing-related cardiopulmonary accidents
among older people is high in winter. The purpose of the present study was to
investigate alterations in physiological characteristics and subjective thermal
sensations of older people when bathing in a cool environment. METHODS: We
assessed the skin temperature, rectal temperature, blood pressure, pulse rate,
body fluid loss (sweat and urine), and subjective thermal responses of 11 older
healthy male and 10 young male volunteers throughout 42 degrees C and 39 degrees
C bathing in a room at 20 degrees C with 50% humidity. RESULTS: At 42 degrees C
bathing, the rectal temperature during bathing and in the post-bathing period
were significantly lower in the older men than in the young men, and skin
temperature during the post-bathing period decreased gradually in the older men.
Systolic blood pressure and pulse rate immediately increased just after entering
42 degrees C water and decreased during bathing in the older men. With the
activities of dressing, systolic blood pressure increased followed by a decrease
during the post-bathing period. Thus, double product (pulse rate * systolic blood
pressure) increased during the bathing period. Although there was no significant
difference in body fluid loss between the older and younger men in 42 degrees C
water, the older men produced significantly less sweat. The older men also
reported feeling less warm after 42 degrees C bathing, and feeling less cold
during the post-bathing period after 39 degrees C bathing. CONCLUSIONS: These
results suggest that hot water bathing during cold seasons might induce more
serious physiological changes in older people. Geriatr Gerontol Int 2017; 17:
2164-2170.
PMID- 28421716
TI - Identification of a new HLA-DQB1*06 allele, HLA-DQB1*06:210, by monoallelic
Sanger sequencing.
AB - Sequence of the novel allele, HLA-DQB1*06:210, differs from HLA-DQB1*06:03:01 by
1 nucleotide exchange in exon 2.
PMID- 28421717
TI - Cognitive profiles in euthymic patients with bipolar disorders: results from the
FACE-BD cohort.
AB - OBJECTIVES: Although cognitive deficits are a well-established feature of bipolar
disorders (BD), even during periods of euthymia, little is known about cognitive
phenotype heterogeneity among patients with BD. METHODS: We investigated
neuropsychological performance in 258 euthymic patients with BD recruited via the
French network of expert centers for BD. We used a test battery assessing six
domains of cognition. Hierarchical cluster analysis of the cross-sectional data
was used to determine the optimal number of subgroups and to assign each patient
to a specific cognitive cluster. Subsequently, subjects from each cluster were
compared on demographic, clinical functioning, and pharmacological variables.
RESULTS: A four-cluster solution was identified. The global cognitive performance
was above normal in one cluster and below normal in another. The other two
clusters had a near-normal cognitive performance, with above and below average
verbal memory, respectively. Among the four clusters, significant differences
were observed in estimated intelligence quotient and social functioning, which
were lower for the low cognitive performers compared to the high cognitive
performers. CONCLUSIONS: These results confirm the existence of several distinct
cognitive profiles in BD. Identification of these profiles may help to develop
profile-specific cognitive remediation programs, which might improve functioning
in BD.
PMID- 28421719
TI - Therapeutic value of renal denervation in cardiovascular disease?
PMID- 28421718
TI - Small serine recombination systems ParA-MRS and CinH-RS2 perform precise excision
of plastid DNA.
AB - Selectable marker genes (SMGs) are necessary for selection of transgenic plants.
However, once stable transformants have been identified, the marker gene is no
longer needed. In this study, we demonstrate the use of the small serine
recombination systems, ParA-MRS and CinH-RS2, to precisely excise a marker gene
from the plastid genome of tobacco. Transplastomic plants transformed with the
pTCH-MRS and pTCH-RS2 vectors, containing the visual reporter gene DsRed flanked
by directly oriented MRS and RS2 recognition sites, respectively, were crossed
with nuclear-genome transformed tobacco plants expressing plastid-targeted ParA
and CinH recombinases, respectively. One hundred per cent of both types of F1
hybrids exhibited excision of the DsRed marker gene. PCR and Southern blot
analyses of DNA from F2 plants showed that approximately 30% (CinH-RS2) or 40%
(ParA-MRS) had lost the recombinase genes by segregation. The postexcision
transformed plastid genomes were stable and the excision events heritable. The
ParA-MRS and CinH-RS2 recombination systems will be useful tools for site
specific manipulation of the plastid genome and for generating marker-free
plants, an essential step for reuse of SMG and for addressing concerns about the
presence of antibiotic resistance genes in transgenic plants.
PMID- 28421720
TI - Enantioselective Organocatalytic Synthesis of a Secoyohimbane-Inspired Compound
Collection with Neuritogenic Activity.
AB - Natural products provide evolutionary validated core structures to inspire the
synthesis of new compound collections endowed with neurite growth-promoting
activity. Rhynchophylline is the major component of Uncaria species, and has been
used to treat neurological diseases in Chinese traditional medicine. Based on the
structure of this spirocyclic secoyohimbane alkaloid, we developed a highly
enantioselective and efficient organocatalyzed synthesis method to provide a
tetracyclic secoyohimbane scaffold incorporating a quaternary and three tertiary
stereogenic centers, in a one-pot multistep reaction sequence. A compound
collection of derived secoyohimbanes was synthesized and expanded by decorating
the periphery of the basic scaffold with additional substituents to increase the
diversity. Evaluation of the different subcollections of secoyohimbanes for
modulation of neurite outgrowth in the SH-SY5Y human cell line led to the
discovery of new compounds that promote neurite outgrowth.
PMID- 28421721
TI - FNAC aided diagnosis of clear cell sarcoma of kidney: Report of two cases in
infants.
AB - Clear cell sarcoma of kidney (CCSK) is a rare aggressive malignant renal neoplasm
with a high metastatic potential. Its outcome has however, improved with the
advent of doxorubicin based neoadjuvant chemotherapy. Here, we present two cases
of CCSK in infants diagnosed on cytology followed by nephrectomy. The first case
presented in the neonatal period and had the unusual histological finding of
islands of cartilage. The second case presented at the age of eight months. The
possibility of CCSK should, therefore, be considered in the differential
diagnoses of renal masses in infants as well as neonates. Diagn. Cytopathol.
2017;45:761-765. (c) 2017 Wiley Periodicals, Inc.
PMID- 28421722
TI - Second Primary Cancer Risk among Kidney Cancer Patients in Korea: A Population
Based Cohort Study.
AB - PURPOSE: Secondary primary cancers (SPCs) commonly arise in patients with renal
cell carcinoma (RCC). We designed the present study to estimate the SPC incidence
in Korean patients with RCC. MATERIALS AND METHODS: The study cohort was
population-based and consisted of 40,347 individuals from the Korean Central
Cancer Registry who were diagnosed with primary renal cancer between 1993 and
2013. Standardized incidence ratios (SIRs) for SPCs were estimated for different
ages at diagnosis, latencies, diagnostic periods, and treatments. RESULTS: For
patients with primary RCC, the risk of developing a SPC was higher than the risk
of developing cancer in the general population (SIR, 1.13; 95% confidence
interval, 1.08 to 1.18). Most cancer types showed higher incidences in patients
with RCC than in the general population. However, the relative incidence of
gastric cancer as an SPC varied by age. Gastric cancer incidence was elevated in
young patients (< 30 years) with RCC, but reduced in older (>= 30) patients with
RCC. Patients with advanced RCC died prematurely, regardless of SPC development.
In contrast, those with early-stage RCC survived for longer periods, although SPC
development affected their post-RCC survival. After SPC development, women had
better survival than men. CONCLUSION: In Korean patients with primary RCC, the
incidence of SPC was 13% higher than the incidence of cancer in the general
population. These findings may play important roles in the conduct of follow-up
evaluations and education for patients with RCC.
PMID- 28421723
TI - Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single
Institute in Korea.
AB - PURPOSE: This study retrospectively evaluated the clinical outcomes and
complications of proton beam therapy (PBT) in a single institution in Korea and
quantitatively analyzed the change in tumor volume after PBT using magnetic
resonance imaging (MRI). MATERIALS AND METHODS: Twenty-four treatment-naive
patients who underwent PBT for choroidal melanoma between 2009 and 2015 were
reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions.
Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and
annually thereafter. The tumor volume was reconstructed and evaluated by stacking
the tumor boundary in each thin-sliced axial T1-weighted image using MIM
software. RESULTS: The median follow-up duration was 36.5 months (range, 9 to 82
months). One patient had suspicious local progression and two patients had
distant metastasis. The 3-year local progression-free survival, distant
metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and
100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03
grade 3-4 toxicities were observed in four patients (16.7%), including one with
neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565+/-0.084
mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12
months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively.
CONCLUSION: The local controlrate and complication profile after PBT in
patientswith choroidal melanoma in Korea were comparable with those reported in a
previous PBT series. The change in tumor volume after PBT exhibited a gradual
regression pattern on MRI.
PMID- 28421724
TI - A National Study of Survival Trends and Conditional Survival in Nasopharyngeal
Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology
and End Results Registry.
AB - PURPOSE: Conditional survival (CS) provides important information on survival for
a period of time after diagnosis. Currently, information on CS patterns of
patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze
survival rate over time and estimate CS for NPC patients using a national
population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC
between 1973 and 2007 with at least 5-year follow-up were identified from the
Surveillance Epidemiology End Results registry. Traditional survival rates and
crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted
survival curves were plotted from the proportional hazards model using the
correct group prognosis method. RESULTS: registry. Traditional survival rates and
crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted
survival curves were plotted from the proportional hazards model using the
correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted
baseline 5-year overall survival improved significantly from 36.0% in patients
diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000
2007 (p < 0.01). CS analysis demonstrated that for every additional year
survived, adjusted probability of surviving the next 5 years increased from 66.7%
(localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to
83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had
survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology,
ethnicity, and stage subgroups initially, but converged with time. CONCLUSION:
Treatment outcomes of NPC patients have greatly improved over the decades.
Increases in CS become more prominent in patients with distant disease than in
those with localized or regional disease as patients survive longer. CS provides
more dynamic prognostic information for patients who have survived a period of
time after diagnosis.
PMID- 28421725
TI - No Association of Positive Superficial and/or Deep Margins with Local Recurrence
in Invasive Breast Cancer Treated with Breast-Conserving Surgery.
AB - PURPOSE: We evaluated the effect of positive superficial and/or deep margin
status on local recurrence (LR) in invasive breast cancer treated with breast
conserving surgery (BCS) followed by radiotherapy. MATERIALS AND METHODS: In
total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS
followed by radiotherapy from January 2000 to December 2008 were included in this
study. These patients were divided into three groups according to margin status:
clear resection margin status for all sections (group 1, n=3,195); positive
margin status in superficial and/or deep sections (group 2, n=121); and positive
peripheral parenchymal margin regardless of superficial and/or deep margin
involvement (group 3, n=87). The LR-free survival between these three groups was
compared and the prognostic role of margin status was analyzed. RESULTS: Across
all groups, age, tumor size, nodal status, and human epidermal growth factor
receptor 2 status did not significantly differ. High grade, positive extensive
intraductal component, hormone receptor positivity, hormone therapy received, and
chemotherapy not received were more prevalent in groups 2 and 3 than in group 1.
Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively.
Multivariate analysis revealed that group 3 was a significant predictor for LR
(hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep
margin was not (HR, 0.66; p=0.57). CONCLUSION: Superficial and/or deep margin
involvement following BCS is not an important predictor for LR.
PMID- 28421727
TI - The epidemic spreading of basal cell carcinoma: incidence trend, demographic
features, characteristics and risk factors in a retrospective study of 8557
lesions in Bologna.
AB - BACKGROUND: Basal cell carcinoma (BCC) has a rising incidence worldwide. The aim
was to evaluate incidence trend, demographic features and risk factors for BCC in
the area of Bologna in northern-central Italy. METHODS: All the consecutive
histopathologically diagnosed BCCs at the Dermatology of the Bologna University
from 1990 to 2014 were retrospectively reviewed. We evaluated the absolute number
of BCCs, the demographic features of patients and the characteristics of BCCs
with statistically significant correlations. RESULTS: During the investigated 25
years, 8,557 BCCs were collected in 7,297 patients. We observed that the
incidence of this cancer, after stabilizing around a plateau of 400 cases/year in
2005, progressively increased onwards reaching a maximum of cases (821) in 2014
(+105.25%), with a 8.32% mean increase per year in those last 9 years. Moreover,
we found a significant correlation (p<0.01%) between gender and the onset of BCC,
between the anatomic location and the occurrence of the tumor, between the onset
of recurrent or new BCCs and sun exposure. CONCLUSIONS: The present study
collects the largest series in the Italian literature focused on demographic
features and characteristics of BCC, highlights its higher increasing incidence
in Bologna and the need to improve preventive strategies to stem the epidemic
diagnosis of BCC.
PMID- 28421726
TI - Selection Criteria for Active Surveillance of Patients with Prostate Cancer in
Korea: A Multicenter Analysis of Pathology after Radical Prostatectomy.
AB - PURPOSE: Korean patients with prostate cancer (PC) typically present with a more
aggressive disease than patients in Western populations. Consequently, it is
unclear if the current criteria for active surveillance (AS) can safely be
applied to Korean patients. Therefore, this study was conducted to define
appropriate selection criteria for AS for patients with PC in Korea. MATERIALS
AND METHODS: We conducted a multicenter retrospective study of 2,126 patients
with low risk PC who actually underwent radical prostatectomy. The primary
outcome was an unfavorable disease, which was defined by non-organ confined
disease or an upgrading of the Gleason score to >= 7 (4+3). Predictive variables
of an unfavorable outcome were identified by multivariate analysis using randomly
selected training samples (n=1,623, 76.3%). We compared our selected criteria to
various Western criteria for the primary outcome and validated our criteria using
the remaining validation sample (n=503, 23.7%). RESULTS: A non-organ confined
disease rate of 14.9% was identified, with an increase in Gleason score >= 7
(4+3) of 8.7% and a final unfavorable disease status of 20.8%. The following
criteria were selected: Gleason score <= 6, clinical stage T1-T2a, prostate
specific antigen (PSA) <= 10 ng/mL, PSA density < 0.15 ng/mL/mL, number of
positive cores <= 2, and maximum cancer involvement in any one core <= 20%. These
criteria provided the lowest unfavorable disease rate (11.7%) when compared to
Western criteria (13.3%-20.7%), and their validity was confirmed using the
validation sample (5.9%). CONCLUSION: We developed AS criteria which are
appropriate for Korean patients with PC. Prospective studies using these criteria
are now warranted.
PMID- 28421728
TI - Oral pigmentation in physiologic conditions, post-inflammatory affections and
systemic diseases.
AB - Melanocytes are found throughout the oral mucosa but usually go unnoticed because
of their relatively low level of pigment production. When focally or generally
active in pigment production or proliferation they may be responsible for several
affections in the oral mucosae ranging from physiologic pigmentation, systemic
diseases to malignant neoplasms. The diagnosis of oral pigmentations (OP) is
usually challenging for the physician, but a careful examination of the oral
cavity may reveal the first manifestation of underlying systemic diseases.
Therefore, a full medical history (including drug assumption and smoking)
together with a general dermatological examination are mandatory and represent
the first approach to OPs. When the diagnosis cannot be reached clinically with
enough certainty, a biopsy for histological examination is needed, also in order
to exclude possible life threatening conditions such as melanoma. Dermoscopy is
another reliable diagnostic tool to make a differential diagnosis between
melanocytic lesions and other conditions and then to manage the follow-up of
patients. Few papers on the subject have been published in the dermatological
literature and the oral cavity is often poorly investigated during routine
dermatological examinations. We therefore decided to perform a review of benign
OPs, classifying them into diffuse (physiological/racial pigmentations, smoker's
melanosis, drug-induced hyperpigmentation, post-inflammatory hyperpigmentation,
black hairy tongue, OPs associated to systemic diseases) and localized (amalgam
tattoo, melanocytic nevi, melanoacanthoma, melanosis) lesions.
PMID- 28421729
TI - Effects of TNF-alpha inhibitors in patients with psoriasis and metabolic
syndrome: a preliminary study.
AB - BACKGROUND: Psoriasis is an inflammatory disease, that is increasingly being
considered as a systemic disorder. Among associated comorbidities, metabolic
syndrome plays an important role. The effects of biological therapies on
metabolic syndrome is controversial. METHODS: Thirty-one psoriatic patients with
metabolic syndrome, eligible to treatment with anti-TNFalpha agents, were
enrolled. Metabolic parameters were measured during 4 subsequent visits, one
every 40 to 60 days. PASI, BSA and DLQI assessed the severity of psoriasis and
the impact on quality of life. RESULTS: We include 31 patients, 18 treated with
etanercept and 13 with adalimumab. Metabolic parameters evaluated at V4 in both
groups showed different trends in the blood glucose values: a slight decrease in
adalimumab group, an increase in etanercept group, with an almost significant
comparison test (p=0.073). Similarly, the lipid profile revealed an opposing
trend, with an increase in triglycerides in adalimumab patients, and a decrease
in the other group, without statistically significant differences. No
statistically significant difference was recorded in HDL cholesterol. An
improvement in systolic and diastolic pressure was appreciated in both groups,
although not significantly. The waist circumference slightly decreased in both
groups. PASI 75 score was reached in 60% of the patients. In addition, BSA and
DLQI improved. CONCLUSIONS: Our study showed a slight improvement of metabolic
parameters, at times with a trend toward significance. Additional long-term
studies and a larger number of patients are needed to more clearly define the
association between psoriasis and cardiovascular disease and understand the
effect of biological therapies on metabolic parameters.
PMID- 28421730
TI - Facies: the value of an old diagnostic tip in pediatric dermatology.
AB - The authors examine what is meant as facies in medicine. After an introduction to
the word's understanding, they move on listing some dermatological conditions
associated to peculiar facies in the child. Starting from atopic dermatitis, the
authors develop an algorithm including Genodermatoses, Neurocutaneous Disorders,
and Multiple Congenital Anomalies Syndromes. They emphasize the distinctive
features of the lesions on the face and their fundamental diagnostic importance.
PMID- 28421731
TI - Intraoperative dexmedetomidine sedation reduces the postoperative agitated
behavior in elderly patients undergoing orthopedic surgery compared to the
propofol sedation.
AB - BACKGROUND: Postoperative agitation or confusion is one of the symptoms of
hyperactive delirium in elderly patients. We retrospectively evaluated the
incidence of postoperative abnormal psychomotor behavior in elderly surgical
patients according to the use of different intraoperative sedative agents:
dexmedetomidine vs. propofol. METHODS: The medical records of 855 elderly
patients, who underwent orthopedic surgery with regional anesthesia between July
2012 and September 2015, were divided into two groups, the dexmedetomidine group
(N.=263) and the propofol group (N.=592), and then evaluated. Agitated behavior
was evaluated as the primary outcome, and patient-, surgery-, and anesthesia
related factors, as well as other postoperative complications, were investigated
as secondary outcomes. To reduce the risk of confounder effects between the two
groups, 263 patients were selected from the propofol group by propensity score
matching. RESULTS: In the propensity-score-matched groups, the incidence of
agitated behavior was lower in the dexmedetomidine group compared with the
propofol group (6 [2.3%] vs. 17 [6.5%], P=0.027). All pre- and postoperative
laboratory values were comparable between the two groups, including hemoglobin,
hematocrit, platelet count, C-reactive protein, electrolytes, creatinine,
glomerular filtration rate, and albumin. Moreover, intraoperative propofol
sedation, older age, higher Charlson comorbidity index, and hip surgery were
found to be significant factors for the occurrence of agitation. CONCLUSIONS:
This study suggests that intraoperative dexmedetomidine sedation, as compared
with propofol sedation, may have a greater beneficial effect in reducing agitated
behavior in elderly patients undergoing orthopedic surgery with regional
anesthesia.
PMID- 28421732
TI - Comparison of absolute fluid restriction versus relative volume redistribution
strategy in low central venous pressure anesthesia in liver resection surgery: a
randomized controlled trial.
AB - BACKGROUND? Lowering central venous pressure (CVP) can decrease blood loss during
liver resection and it is associated with improved outcomes. Multiple CVP
reducing maneuvers have been described, but direct comparison of their
effectiveness and safety has never been performed. METHODS? Patients undergoing
resections of two or more liver segments were equally randomized to absolute
fluid restriction (AR, N.=17) or relative volume redistribution group (RR,
N.=17). The ease of reaching low CVP, blood loss, morbidity and mortality were
assessed. Besides, the effect of Pringle maneuver and utility of stroke volume
variation (SVV) were analyzed. RESULTS? Both methods of CVP reduction were
equally effective (0.7+/-0.9 vs. 0.9+/-1.0 protocolized steps in the AR and RR
group; P=0.356) and safe (no difference in observed blood loss, intraoperative
hemodynamic parameters, lactate levels, morbidity and mortality). Patients in the
AR group received smaller amount of fluids in the pre-resection period (120 (100
150) vs. 600 (500-700) mL; P<0.001), and had slightly longer hospital stay (10 [8
14] vs. 8 [7-11]; P=0.045). Low CVP was predicted by SVV>10% with 81.4%
sensitivity and 77.1% specificity. Reduced blood loss and transfusion rate was
observed when Pringle maneuver was used. CONCLUSIONS? In our study, absolute
fluid restriction and relative volume redistribution seemed to be equally
effective and safe methods of lowering CVP in patients undergoing liver
resection. According to our data high SVV might be considered as a low CVP
replacement. Pringle maneuver reduced blood loss and transfusion requirement.
PMID- 28421733
TI - Beyond high-flow oxygen therapy to manage the hazards of intubation and prevent
desaturation.
PMID- 28421734
TI - Pediatric cuffed tracheal tubes: the advantage of a deflation-in-action maneuver.
PMID- 28421735
TI - Self-Healable and Cold-Resistant Supercapacitor Based on a Multifunctional
Hydrogel Electrolyte.
AB - Excellent self-healability and cold resistance are attractive properties for a
portable/wearable energy-storage device. However, achieving the features is
fundamentally dependent on an intrinsically self-healable electrolyte with high
ionic conduction at low temperature. Here we report such a hydrogel electrolyte
comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding.
Since its dynamically cross-linked alginate network can tolerate high-content
inorganic salts, the electrolyte possesses excellent healing
efficiency/cyclability but also high ionic conduction at both room temperature
and low temperature. A supercapacitor with the multifunctional hydrogel
electrolyte completely restores its capacitive properties even after
breaking/healing for 10 cycles without external stimulus. At a low temperature of
-10 degrees C, the capacitor is even able to maintain at least 80% of its room
temperature capacitance. Our investigations offer a strategy to assemble self
healable and cold-resistant energy storage devices by using a multifunctional
hydrogel electrolyte with rationally designed polymeric networks, which has
potential application in portable/wearable electronics, intelligent apparel or
flexible robot, and so on.
PMID- 28421736
TI - Enhancing the Bioactivity of Yttria-Stabilized Tetragonal Zirconia Ceramics via
Grain-Boundary Activation.
AB - Yttria-stabilized tetragonal zirconia (Y-TZP) has been proposed as a potential
dental implant because of its good biocompatibility, excellent mechanical
properties, and distinctive aesthetic effect. However, Y-TZP cannot form chemical
bonds with bone tissue because of its biological inertness, which affects the
reliability and long-term efficacy of Y-TZP implants. In this study, to improve
the bioactivity of Y-TZP ceramics while maintaining their good mechanical
performance, Y-TZP was modified by grain-boundary activation via the infiltration
of a bioactive glass (BG) sol into the surface layers of Y-TZP ceramics under
different negative pressures (atmospheric pressure, -0.05 kPa, and -0.1 kPa),
followed by gelling and sintering. The in vitro bioactivity, mechanical
properties, and cell behavior of the Y-TZP with improved bioactivity were
systematically investigated using X-ray diffraction (XRD), scanning electron
microscopy (SEM), energy-dispersive spectrometry (EDS), electron probe
microanalysis (EPMA), and Raman spectroscopy. The results of the bioactivity test
conducted by immersing Y-TZP in simulated body fluid (SBF) showed that a bonelike
apatite layer was produced on the entire surface. The mechanical properties of
the modified Y-TZP decreased as the negative pressure in the BG-infiltration
process increased relative to those of the Y-TZP blank group. However, the
samples infiltrated with the BG sol under -0.05 kPa and atmospheric pressure
still retained good mechanical performance. The cell-culture results revealed
that the bioactive surface modification of Y-TZP could promote cell adhesion and
differentiation. The present work demonstrates that the bioactivity of Y-TZP can
be enhanced by grain-boundary activation, and the bioactive Y-TZP is expected to
be a potential candidate for use as a dental implant material.
PMID- 28421737
TI - Modeling of Stresses and Strains during (De)Lithiation of Ni3Sn2-Coated Nickel
Inverse-Opal Anodes.
AB - Tin alloy-based anodes supported by inverse-opal nanoscaffolds undergo large
volume changes from (de)lithiation during cyclic battery (dis)charging, affecting
their mechanical stability. We perform continuum mechanics-based simulation to
study the evolution of internal stresses and strains as a function of the
geometry of the active layer(s): (i) thickness of Ni3Sn2 single layer (30 and 60
nm) and (ii) stacking sequence of Ni3Sn2 and amorphous Si in bilayers (60 nm
thick). For single Ni3Sn2 active layers, a thinner layer displays higher strains
and stresses, which are relevant to mechanical stability, but causes lower
strains and stresses in the Ni scaffold. For Ni3Sn2-Si bilayers, the stacking
sequence significantly affects the deformation of the active layers and thus its
mechanical stability due to different lithiation behaviors and volume changes.
PMID- 28421738
TI - Targeting the Nrf2/Amyloid-Beta Liaison in Alzheimer's Disease: A Rational
Approach.
AB - Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, a linear linkage
between amyloid-beta peptide (Abeta) and the disease onset and progression has
recently been questioned. In this context, the crucial partnership between Abeta
and Nrf2 pathways is acquiring paramount importance, offering prospects for
deciphering the Abeta-centered disease network. Here, we report on a new class of
antiaggregating agents rationally designed to simultaneously activate
transcription-based antioxidant responses, whose lead 1 showed interesting
properties in a preliminary investigation. Relying on the requirements of Abeta
recognition, we identified the catechol derivative 12. In SH-SY5Y neuroblastoma
cells, 12 combined remarkable free radical scavenger properties to the ability to
trigger the Nrf2 pathway and induce the Nrf2-dependent defensive gene NQO1 by
means of electrophilic activation of the transcriptional response. Moreover, 12
prevented the formation of cytotoxic stable oligomeric intermediates, being
significantly more effective, and per se less toxic, than prototype 1. More
importantly, as different chemical features were exploited to regulate Nrf2 and
Abeta activities, the two pathways could be tuned independently. These findings
point to compound 12 and its derivatives as promising tools for investigating the
therapeutic potential of the Nrf2/Abeta cellular network, laying foundation for
generating new drug leads to confront AD.
PMID- 28421740
TI - Enhancing the Performance of Quantum Dot Light-Emitting Diodes Using Room
Temperature-Processed Ga-Doped ZnO Nanoparticles as the Electron Transport Layer.
AB - Colloidal ZnO nanoparticle (NP) films are recognized as efficient electron
transport layers (ETLs) for quantum dot light-emitting diodes (QD-LEDs) with good
stability and high efficiency. However, because of the inherently high work
function of such films, spontaneous charge transfer occurs at the QD/ZnO
interface in such a QD-LED, thus leading to reduced performance. Here, to improve
the QD-LED performance, we prepared Ga-doped ZnO NPs with low work functions and
tailored band structures via a room-temperature (RT) solution process without the
use of bulky organic ligands. We found that the charge transfer at the interface
between the CdSe/ZnS QDs and the doped ZnO NPs was significantly weakened because
of the incorporated Ga dopants. Remarkably, the as-assembled QD-LEDs, with Ga
doped ZnO NPs as the ETLs, exhibited superior luminances of up to 44 000 cd/m2
and efficiencies of up to 15 cd/A, placing them among the most efficient red
light QD-LEDs ever reported. This discovery provides a new strategy for
fabricating high-performance QD-LEDs by using RT-processed Ga-doped ZnO NPs as
the ETLs, which could be generalized to improve the efficiency of other
optoelectronic devices.
PMID- 28421739
TI - Ultraefficient Cap-Exchange Protocol To Compact Biofunctional Quantum Dots for
Sensitive Ratiometric Biosensing and Cell Imaging.
AB - An ultraefficient cap-exchange protocol (UCEP) that can convert hydrophobic
quantum dots (QDs) into stable, biocompatible, and aggregation-free water
dispersed ones at a ligand:QD molar ratio (LQMR) as low as 500, some 20-200-fold
less than most literature methods, has been developed. The UCEP works
conveniently with air-stable lipoic acid (LA)-based ligands by exploiting tris(2
carboxylethyl phosphine)-based rapid in situ reduction. The resulting QDs are
compact (hydrodynamic radius, Rh, < 4.5 nm) and bright (retaining > 90% of
original fluorescence), resist nonspecific adsorption of proteins, and display
good stability in biological buffers even with high salt content (e.g., 2 M
NaCl). These advantageous properties make them well suited for cellular imaging
and ratiometric biosensing applications. The QDs prepared by UCEP using
dihydrolipoic acid (DHLA)-zwitterion ligand can be readily conjugated with octa
histidine (His8)-tagged antibody mimetic proteins (known as Affimers). These QDs
allow rapid, ratiometric detection of the Affimer target protein down to 10 pM
via a QD-sensitized Forster resonance energy transfer (FRET) readout signal.
Moreover, compact biotinylated QDs can be readily prepared by UCEP in a facile,
one-step process. The resulting QDs have been further employed for ratiometric
detection of protein, exemplified by neutravidin, down to 5 pM, as well as for
fluorescence imaging of target cancer cells.
PMID- 28421741
TI - Uphill Water Transport on a Wettability-Patterned Surface: Experimental and
Theoretical Results.
AB - In nature, there exist many functional water-controlling surfaces, such as the
water-repellent surface of lotus leaves, the superhydrophobic water-adhesive
surface of rose petals, the water-harvesting surface of a beetle's back, and the
water-transporting surface of the legs of Ligia exotica. These natural surfaces
suggest that surface chemistry and hierarchical structures are essential for
controlling the water behavior. We have reported the preparation of
superhydrophobic and antireflection silicon nanospike-array structures using self
organized honeycomb-patterned films as three-dimensional dry-etching masks.
Moreover, the surface wettability of the silicon nanospike-array structures can
be easily transformed from superhydrophobic to superhydrophilic by changes in the
surface chemistry. In this report, we show the preparation of water-controlling
surfaces, such as water-harvesting and water-transporting surfaces, by the
wettability patterning of silicon nanostructured surfaces. We prepared honeycomb
patterned films for dry-etching masks made from polystyrene and an amphiphilic
polymer by casting a chloroform solution. After the fixation of the top layer of
the honeycomb-patterned films on a single-crystal silicon substrate, reactive ion
etching was performed. The as-prepared silicon nanospike-array structure showed
superhydrophobicity, and the water contact angles were over 170 degrees . After
UV-O3 treatment with photomasks, only the UV-irradiated surfaces showed
superhydrophilicity, suggesting that we can obtain superhydrophobic- and
superhydrophilic-patterned surfaces for which the patterns are the same as those
of the photomasks. On the basis of these wettability-patterned surfaces, we
demonstrated water harvesting by superhydrophilic dot-patterned surfaces and
water transportation against gravity by superhydrophilic triangular-patterned
surfaces. In particular, we investigated uphill water transport through the
motion of droplets on tilting slopes based on the equation of motion. These
results suggested that we can obtain superior microfluidic devices suitable for
various applications through the use of optional wettability patterns.
PMID- 28421742
TI - Mid-Gap States and Normal vs Inverted Bonding in Luminescent Cu+- and Ag+-Doped
CdSe Nanocrystals.
AB - Mid-gap luminescence in copper (Cu+)-doped semiconductor nanocrystals (NCs)
involves recombination of delocalized conduction-band electrons with copper
localized holes. Silver (Ag+)-doped semiconductor NCs show similar mid-gap
luminescence at slightly (~0.3 eV) higher energy, suggesting a similar
luminescence mechanism, but this suggestion appears inconsistent with the large
difference between Ag+ and Cu+ ionization energies (~1.5 eV), which should make
hole trapping by Ag+ highly unfavorable. Here, Ag+-doped CdSe NCs (Ag+:CdSe) are
studied using time-resolved variable-temperature photoluminescence (PL)
spectroscopy, magnetic circularly polarized luminescence (MCPL) spectroscopy, and
time-dependent density functional theory (TD-DFT) to address this apparent
paradox. In addition to confirming that Ag+:CdSe and Cu+:CdSe NCs display similar
broad PL with large Stokes shifts, we demonstrate that both also show very
similar temperature-dependent PL lifetimes and magneto-luminescence. Electronic
structure calculations further predict that both dopants generate similar
localized mid-gap states. Despite these strong similarities, we conclude that
these materials possess significantly different electronic structures.
Specifically, whereas photogenerated holes in Cu+:CdSe NCs localize primarily in
Cu(3d) orbitals, formally oxidizing Cu+ to Cu2+, in Ag+:CdSe NCs they localize
primarily in 4p orbitals of the four neighboring Se2- ligands, and Ag+ is not
oxidized. This difference reflects a shift from "normal" to "inverted" bonding
going from Cu+ to Ag+. The spectroscopic similarities are explained by the fact
that, in both materials, photogenerated holes are localized primarily within
covalent [MSe4] dopant clusters (M = Ag+, Cu+). These findings reconcile the
similar spectroscopies of Ag+- and Cu+-doped semiconductor NCs with the vastly
different ionization potentials of their Ag+ and Cu+ dopants.
PMID- 28421743
TI - Double-Enzymes-Mediated Bioluminescent Sensor for Quantitative and Ultrasensitive
Point-of-Care Testing.
AB - We report an ultrasensitive, quantitative, and rapid bioluminescent immunosensor
(ABS) for point-of-care testing (POCT) of the disease biomarker in clinical
samples using double enzymes including alkaline phosphatase (ALP) and luciferase.
In the presence of the biomarker, the ALP attached on the surface of immuno
nanocomplex dephosphorylates adenine triphosphate (ATP), subsequently inhibiting
the ATP-luciferin-luciferase bioluminescent reaction. The highly sensitive
response of ATP (picomolar level) allows for ultrasensitive detection of
biomarker via the effective change of the bioluminescence intensity through ALP-
and luciferase-catalyzed reactions, which can be quantitatively determined by a
portable ATP detector. This ABS fulfills the criteria for POCT that performs
sensitive (femtomolar level of biomarkers) and quantitative measurement quickly
(less than 1 h) with minimal equipment (portable detector).
PMID- 28421744
TI - A Mini HIP HOP Assay Uncovers a Central Role for Copper and Zinc in the
Antifungal Mode of Action of Allicin.
AB - Garlic contains the organosulfur compound allicin which exhibits potent
antifungal activity. Here we demonstrate the use of a highly simplified yeast
chemical genetic screen to characterize its mode of action. By screening 24
validated yeast gene deletion "signature" strains for which hypersensitivity is
characteristic for common antifungal modes of action, yeast lacking the high
affinity Cu2+ transporter Ctr1 was found to be hypersensitive to allicin.
Focusing on transition metal related genes identified two more hypersensitive
strains lacking the Cu2+ and Zn2+ transcription factors Mac1 and Zap1.
Hypersensitivity in these strains was reversed by the addition of Cu2+ and Zn2+
ions, respectively. The results suggest the antifungal activity of allicin is
mediated through restricted Cu2+ and Zn2+ uptake or inhibition of Cu2+ and Zn2+
metalloproteins. As certain antimicrobial modes of action are much more common
than others, the approach taken here provides a useful way to identify them early
on.
PMID- 28421745
TI - Molecular Approach to the Synergistic Effect on Astringency Elicited by Mixtures
of Flavanols.
AB - The interactions between salivary proteins and wine flavanols (catechin,
epicatechin, and mixtures thereof) have been studied by HPLC-DAD, isothermal
titration microcalorimetry, and molecular dynamics simulations. Chromatographic
results suggest that the presence of these flavanol mixtures could facilitate the
formation of precipitates to the detriment of soluble aggregates. Comparison
between the thermodynamic parameters obtained showed remarkably higher negative
values of DeltaG in the system containing the mixture of both flavanols in
comparison to the systems containing individual flavanols, indicating a more
favorable scenario in the mixing system. Also, the apparent binding constants
were higher in this system. Furthermore, molecular dynamics simulations suggested
a faster and greater cooperative binding of catechin and epicatechin to IB714
peptides when both types of flavanols are present simultaneously in solution.
PMID- 28421746
TI - Multifunctional Enzymatically Generated Hydrogels for Chronic Wound Application.
AB - The healing of chronic wounds requires intensive medical intervention at huge
healthcare costs. Dressing materials should consider the multifactorial nature of
these wounds comprising deleterious proteolytic and oxidative enzymes and high
bacterial load. In this work, multifunctional hydrogels for chronic wound
application were produced by enzymatic cross-linking of thiolated chitosan and
gallic acid. The hydrogels combine several beneficial to wound healing
properties, controlling the matrix metalloproteinases (MMPs) and myeloperoxidase
(MPO) activities, oxidative stress, and bacterial contamination. In vitro studies
revealed above 90% antioxidant activity, and MPO and collagenase inhibition by up
to 98 and 23%, respectively. Ex vivo studies with venous leg ulcer exudates
confirmed the inhibitory capacity of the dressings against MPO and MMPs.
Additionally, the hydrogels reduced the population of the most frequently
encountered in nonhealing wounds bacterial strains. The stable at physiological
conditions and resistant to lysozyme degradation hydrogels showed high
biocompatibility with human skin fibroblasts.
PMID- 28421747
TI - Multifunctional Probe Based on Cationic Conjugated Polymers for Nitroreductase
Related Analysis: Sensing, Hypoxia Diagnosis, and Imaging.
AB - Nitroreductase (NTR) is overexpressed in hypoxic tumors. Moreover, hypoxia is
usually considered as the most important feature of various diseases. Thus, it is
important to build a sensitive and selective method for NTR detection and hypoxia
diagnosis. Herein, a new cationic conjugated polymer (PBFBT-NP) with p
nitrophenyl group in the side chain was designed and synthesized as a fluorescent
probe for the detection of NTR. In the absence of NTR, the fluorescence of PBFBT
NP was quenched due to photoinduced electron transfer (PET). On the contrary, in
the presence of NTR, NTR can specifically react with p-nitrophenyl group to form
p-aminophenyl group, which leads to the PET being inhibited and the polymer's
fluorescence significantly increasing (>110-fold). The sensitive and selective
NTR sensing method in vitro is thus constructed with a low detection limit of 2.9
ng/mL. Moreover, the hypoxic status of tumor cells can be visualized by
fluorescence bioimaging with very low cytotoxicity. Interestingly, the probe was
successfully used for imaging an NTR-expressed microorganism, such as E. coli,
and showed excellent antibacterial activity against E. coli under white light
irradiation. In brief, this multifunctional probe is promising for widespread use
in NTR-related biological analysis.
PMID- 28421748
TI - Potential Contribution of Fish Feed and Phytoplankton to the Content of Volatile
Terpenes in Cultured Pangasius (Pangasianodon hypophthalmus) and Tilapia
(Oreochromis niloticus).
AB - Geosmin and 2-methylisoborneol are the most recognized off-flavors in freshwater
fish, but terpenes may also contribute off-flavor in fish. We identified six
monoterpenes, 11 sesquiterpenes, and three terpene-related compounds in pangasius
and tilapia from aquaculture farms in Bangladesh. The concentrations of most of
the volatiles were below published odor thresholds, except for alpha-pinene,
limonene, beta-caryophyllene, alpha-humulene, and beta-ionone in tilapia, and
limonene and beta-ionone in pangasius. To identify sources of the terpenes,
terpene profiles of fish feed and phytoplankton in the ponds were analyzed. In
feed and mustard cake (feed ingredient), five monoterpenes and two sesquiterpenes
were identified, and five of these compounds were also detected in the fish. In
phytoplankton, 11 monoterpenes were found and three also occurred in the fish.
The higher number of terpenes common to both fish and feed, than to fish and
phytoplankton, suggests that feed was a more abundant source of odor-active
terpenes in the fish than phytoplankton.
PMID- 28421749
TI - Design of Multifunctional Nanogate in Response to Multiple External Stimuli Using
Amphiphilic Diblock Copolymer.
AB - Nature uses the interplay between hydrophobic and electrostatic interactions of
disordered proteins to orchestrate complicated molecular gates such as the
nuclear pore complex to control the transport of biological masses. Inspired by
nature, we here theoretically show that well-defined gate shape, sensitive
response to pH and salt concentration, and selectivity in cargo transport can be
simultaneously achieved by grafting amphiphilic diblock copolymers made of
sequence-controlled hydrophobic and ionizable monomers on the inner surface of
solid-state nanopore. As a result, multiple functions such as ionic gating and
molecular filtering can be implemented into one single copolymer nanogate. The
gate structure and thermodynamics is a result of the self-assembly of the
sequence-designed copolymer in the confined geometry that minimizes the free
energy of the system. Our theory further predicts a phase transition and
discontinuous charge regulation of the confined copolymer that allows logical
gating in biosensors and nanofluidic devices. As an example of application, a
nanolocker with the potential of molecular pumping has also been designed with
the cooperation of two amphiphilic copolymer gates. Our results highlight the
importance of polymer sequence in nanogating, and these insights can be used to
guide the rational design of polymer-coated smart nanopores.
PMID- 28421750
TI - How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis
of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency,
and Many Consistently Inactive Compounds.
AB - Undetected pan-assay interference compounds (PAINS) with false-positive
activities in assays often propagate through medicinal chemistry programs and
compromise their outcomes. Although a large number of PAINS have been classified,
often on the basis of individual studies or chemical experience, little has been
done so far to systematically assess their activity profiles. Herein we report a
large-scale analysis of the behavior of PAINS in biological screening assays.
More than 23 000 extensively tested compounds containing PAINS substructures were
detected, and their hit rates were determined. Many consistently inactive
compounds were identified. The hit frequency was low overall, with median values
of two to five hits for PAINS tested in hundreds of assays. Only confined subsets
of PAINS produced abundant hits. The same PAINS substructure was often found in
consistently inactive and frequently active compounds, indicating that the
structural context in which PAINS occur modulates their effects.
PMID- 28421751
TI - Formation and Characterization of Homoleptic Thorium Isocyanide Complexes.
AB - Homoleptic thorium isocyanide complexes have been prepared via the reactions of
laser-ablated thorium atoms and (CN)2 in a cryogenic matrix, and the structures
of the products were characterized by infrared spectroscopy and theoretical
calculations. Thorium atoms reacted with (CN)2 under UV irradiation to form the
oxidative addition product Th(NC)2, which was calculated to have closed-shell
singlet ground state with a bent geometry. Further reaction of Th(NC)2 and (CN)2
resulted in the formation of Th(NC)4, a molecule with a tetrahedral geometry.
Minor products such as ThNC and Th(NC)3 were produced upon association reactions
of CN with Th and Th(NC)2. Homoleptic thorium cyanide isomers Th(CN)x (x = 1-4)
are predicted to be less stable than the corresponding isocyanides. The C-N
stretches of thorium cyanides were calculated to be between 2170 and 2230 cm-1 at
the B3LYP level, more than 120 cm-1 higher than the N-C stretches of isocyanides
and with much weaker intensities. No experimental absorptions appeared where
Th(CN)x should be observed.
PMID- 28421752
TI - Consecutive Sonogashira Coupling and Hydroamination Cyclization for the Synthesis
of Isoindolo[1,2-b]quinazolin-10(12H)-ones Catalyzed by CuI/l-Proline.
AB - A consecutive Sonogashira coupling reaction, acetylene hydroamination cyclization
of 2-(2-bromophenyl)quinazolin-4(3H)-ones and terminal alkynes, is described
catalyzed by CuI/l-proline in the presence of Cs2CO3. This procedure provided a
facile method for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-one
derivatives in good yields.
PMID- 28421753
TI - Ruthenium(II)-Catalyzed Redox-Neutral [3+2] Annulation of Indoles with Internal
Alkynes via C-H Bond Activation: Accessing a Pyrroloindolone Scaffold.
AB - Ru(II)-catalyzed redox-neutral [3+2] annulation reactions of N-ethoxycarbamoyl
indoles and internal alkynes via C-H bond activation are reported. This method
features a broad internal alkyne scope, including various aryl/alkyl-,
alkyl/alkyl-, and diaryl-substituted alkynes, good to excellent regioselectivity,
diverse functional group tolerance, and mild reaction conditions. The N
ethoxycarbamoyl directing group, temperature, CsOAc, and ruthenium catalyst
proved to be crucial for conversion and high regioselectivity. Additionally,
preliminary mechanistic experiments were conducted, and a possible mechanism was
proposed.
PMID- 28421754
TI - Orbicularisine: A Spiro-Indolothiazine Isolated from Gills of the Tropical
Bivalve Codakia orbicularis.
AB - A novel spiro-indolofuranone fused to a thiazine skeleton, orbicularisine (1),
was isolated from gills of the mollusk Codakia orbicularis. The isolation and
structure elucidation using spectroscopic evidence including mass and NMR
spectroscopy are described. The final structure of 1 was supported by key HMBC
correlation.
PMID- 28421755
TI - Increasing Radical Character of Large [n]cyclacenes Unveiled by Wave Function
Theory.
AB - We have investigated the radicality and the vertical singlet-triplet energy gap
of [n]cyclacenes (cyclic polyacenes) as a function of the system size for n even,
from 6 to 22. The calculations are performed using the complete active space self
consistent field method and second-order n-electron valence perturbation theory.
We present a systematic way for the selection of the active space in order to
have a balanced description of the wave function as the size of the system
increases. Moreover, we provide didactic insight into the failure of an approach
based on a minimal active space. We find that the ground state is an open-shell
singlet and its multireference character increases progressively with n. The
singlet-triplet gap decreases as a function of the system size and approaches a
finite positive value for the limit n -> infinity. Finally, an analysis based on
the one-particle reduced density matrix suggests a polyradical character for the
largest cyclacenes.
PMID- 28421756
TI - Reactions of Copper and Silver Cations with Carbon Dioxide: An Infrared
Photodissociation Spectroscopic and Theoretical Study.
AB - The reaction of copper and silver cations with carbon dioxide was studied by mass
selected infrared photodissociation spectroscopy. Quantum chemical calculations
were performed on these products, which aided the experimental assignments of the
infrared spectra and helped to elucidate the geometrical and electronic
structures. The Cu+ and Ag+ cations bind to an oxygen atom of CO2 in an end-on
configuration via a charge-quadrupole electrostatic interaction in the [M(CO2)n]+
complexes. The formation of oxide-carbonyl and carbonyl-carbonate structures is
not favored for the interaction of CO2 with Cu+ and Ag+. For n = 3 and 4, the n +
0 structure is preferred. [Note on the nomenclature: Using i + j, i denotes the
number of CO2 molecules in the first coordination shell, and j denotes the number
of CO2 molecules in the second coordination shell.] The two nearly energy
identical n + 0 and (n - 1) + 1 structures coexist in n = 5 and 6. While the six
coordinated structure is favored for [Cu(CO2)n=7,8]+, the n + 0 configuration is
dominated in [Ag(CO2)n=7,8]+. The reaction of CO2 with the cationic metal atoms
has been compared to that with the neutral and anionic metal atoms, which would
have important implications for understanding the interaction of CO2 with
reduction catalysts and rationally designing catalysts for CO2 reduction based on
cost-effective transition metals.
PMID- 28421757
TI - A Bulky Disulfoxide Ligand for Pd-Catalyzed Oxidative Allylic C-H Amination with
2,2,2-Trichloroethyl Tosyl Carbamate.
AB - Challenging substrates and conditions in homogeneous catalysis pose stringent
demands on the ligands used. A novel, bulky, 1-adamantyl-substituted disulfoxide
ligand designed after a systematic evaluation of the electronic and steric
properties of disulfoxide substituents permits the allylic oxidative C-N coupling
reaction to proceed at lower catalyst loading while requiring a smaller excess of
reagents. Additionally, this ligand improves the yields when TsNHCOOCH2CCl3, a
novel reagent that permits deprotection of the products under both acidic and
basic conditions, is used.
PMID- 28421758
TI - Copper(II)-Mediated Chelation-Assisted Regioselective N-Naphthylation of Indoles,
Pyrazoles and Pyrrole through Dehydrogenative Cross-Coupling.
AB - A copper-mediated picolinamide directed regioselective cross-coupling of
naphthylamines with azoles is developed via C-H functionalization and C-N bond
formation. The reaction of indoles leads to the formation of chiral C-N cross
coupled products with functional group tolerance. These reaction conditions can
also be extended to the cross-coupling of pyrazole and pyrrole scaffolds.
PMID- 28421759
TI - Is the Accuracy of Density Functional Theory for Atomization Energies and
Densities in Bonding Regions Correlated?
AB - The development of approximate exchange-correlation functionals is critical for
modern density functional theory. A recent analysis of atomic systems suggested
that some modern functionals are straying from the path toward the exact
functional because electron densities are becoming less accurate while energies
are becoming more accurate since the year 2000. To investigate this trend for
more chemically relevant systems, the electron densities in the bonding regions
and the atomization energies are analyzed for a series of diatomic molecules with
90 different functionals. For hybrid generalized gradient approximation
functionals developed since the year 2000, the errors in densities and
atomization energies are decoupled; the accuracy of the energies remains
relatively consistent while the accuracy of the densities varies significantly.
Such decoupling is not observed for generalized gradient and meta-generalized
gradient approximation functionals. Analysis of electron densities in bonding
regions is found to be important for the evaluation of functionals for chemical
systems.
PMID- 28421760
TI - Transient Resonance Raman Spectroscopy of a Light-Driven Sodium-Ion-Pump
Rhodopsin from Indibacter alkaliphilus.
AB - Sodium-ion-pump rhodopsin (NaR) is a microbial rhodopsin that transports Na+
during its photocycle. Here we explore the photocycle mechanism of NaR from
Indibacter alkaliphilus with transient absorption and transient resonance Raman
spectroscopy. The transient absorption data indicate that the photocycle of NaR
is K (545 nm) -> L (490 nm)/M (420 nm) -> O1 (590 nm) -> O2 (560 nm) -> NaR,
where the L and M are formed as equilibrium states. The presence of K, L, M, and
O intermediates was confirmed by the resonance Raman spectra with 442 and 532 nm
excitation. The main component of the transient resonance Raman spectra was due
to L which contains a 13-cis retinal protonated Schiff base. The presence of an
enhanced hydrogen out-of-plane band as well as its sensitivity to the H/D
exchange indicate that the retinal chromophore is distorted near the Schiff base
region in L. Moreover, the retinal Schiff base of the L state forms a hydrogen
bond that is stronger than that of the dark state. These observations are
consistent with a Na+ pumping mechanism that involves a proton transfer from the
retinal Schiff base to a key aspartate residue (Asp116 in Krokinobacter eikastus
rhodopsin 2) in the L/M states.
PMID- 28421761
TI - Diversity-Oriented One-Pot Synthesis to Construct Functionalized Chroman-2-one
Derivatives and Other Heterocyclic Compounds.
AB - The asymmetric organocatalyzed diversity-oriented one-pot synthesis has been
developed to construct chroman-2-one derivatives and other heterocyclic compounds
with excellent efficiency and stereoselectivity. The reactions represent a
challenging issue, since it altered the inherent selectivity profiles exhibited
by the substrates of 2-hydroxycinnamaldehyde 1 and trans-beta-nitrostyrene 2,
which was previously reported as the asymmetric oxa-Michael-Michael cascade to
generate chiral chromans. It should be noted that polycyclic O,O-acetal
containing compounds, which are found in numerous natural products and
biologically interesting molecules, could also be achieved in good yields with
excellent enantioselectivity as a single diastereoisomer with five continuous
stereogenic centers.
PMID- 28421762
TI - Cinchona Alkaloid Catalyzed Enantioselective [4 + 2] Annulation of Allenic Esters
and in Situ Generated ortho-Quinone Methides: Asymmetric Synthesis of
Functionalized Chromans.
AB - A novel enantioselective [4 + 2] annulation of the allenoates having a unique
positive ortho-effect with in situ generated ortho-quinone methides has been
developed under the catalysis of Cinchona alkaloid. This chiral amine-catalyzed
reaction provides an alternative route to asymmetric catalytic construction of
synthetically interesting, highly functionalized chiral chromans in good to
excellent enantioselectivities (up to 97% ee).
PMID- 28421763
TI - Synthetic Approaches to the New Drugs Approved During 2015.
AB - New drugs introduced to the market every year represent privileged structures for
particular biological targets. These new chemical entities (NCEs) provide insight
into molecular recognition while serving as leads for designing future new drugs.
This annual review describes the most likely process-scale synthetic approaches
to 29 new chemical entities (NCEs) that were approved for the first time in 2015.
PMID- 28421764
TI - Total Synthesis of the Claimed Structure of (+/-)-Hyptinin and Structural
Revision of Natural Hyptinin.
AB - A total synthesis of (+/-)-hyptinin was achieved via a convergent route using the
key phosphonate, cyclic ketone, and aryl Grignard components. The 1H and 13C NMR
spectra of natural hyptinin did not agree with those of the synthesized compound.
In particular, there were considerable differences between the signals assigned
to the protons and carbons surrounding the lactone carbonyl group for the natural
and synthesized compounds. The NMR data strongly suggested that the naturally
occurring compound, hyptinin, was a structural isomer of the synthesized
compound. The structure of the natural compound was eventually established as (+)
beta-apopicropodophyllin, based on the synthesis results.
PMID- 28421765
TI - Singlet Fission in Weakly Interacting Acene Molecules.
AB - The energy conversion in solar cells has conventionally been limited by the
Shockley-Queisser limit. Singlet fission (SF), a decay mechanism where a single
excited singlet state is converted into two triplet states, can drastically
improve this efficiency. For the most part, observation of SF has been limited to
crystalline structures in solids and films, where strong ordering was present.
Here we report on singlet fission in a disordered system where organic
chromophores are distributed on the surface of a rare gas cluster. In this case,
the intermolecular distances and degree of excitation can be varied to obtain
their effects on the rate of singlet fission. We introduce a kinematic model that
takes into account the details of the geometrical arrangement of the system as
well as the time-dependent populations of the relevant states of each molecule
and evaluate the trends obtained by SF on the experimental observables.
PMID- 28421766
TI - Total Synthesis of Lamellarin D Trimethyl Ether, Lamellarin D, and Lamellarin H.
AB - Total syntheses of three different lamellarins have been accomplished using a
Ru(II)-catalyzed (3 + 2) annulation strategy to construct the central pyrrole
ring. The striking features of this synthesis are the use of PEG-400 as a green
solvent for the (3 + 2) annulation reaction and multiple catalytic reactions with
excellent overall yield. The present route also enables the synthesis of various
lamellarin analogues devoid of a B ring.
PMID- 28421767
TI - Base Layer Influence on Protonated Aminosilane Gradient Wettability.
AB - Protonated amine gradients have been prepared on silicon wafers via programmed
controlled rate infusion (CRI) with varying degrees of hydrophobicity and
characterized by X-ray photoelectron spectroscopy (XPS) and static and Wilhelmy
plate dynamic contact angle measurements. Initially, base layers were spin coated
from sols containing tetramethoxysilane (TMOS) and either phenyltrimethoxysilane
(PTMOS), dimethyldimethoxysilane (DMDMOS), or octyltrimethoxysilane (OTMOS, C8).
Amine gradients were then prepared from 3-aminopropyltriethoxysilane (APTEOS) via
CRI. Gradients were exposed to concentrated HCl vapor for amine protonation. XPS
showed that NH2 functional groups were distributed in a gradient fashion as a
result of CRI controlling the time of exposure to APTEOS. Interestingly, the
overall extent of N modification depended on the type of base layer used for
gradient formation. The C8-derived base layer had about half the amount of
nitrogen on the surface as compared to those prepared from TMOS, which was
attributed to a reduction in the number and accessibility of surface silanol
groups. The wettability and contact angle (CA) hysteresis were also dependent on
the base layer and varied along the length of the gradient. The greatest CA
change across the length of the gradient was observed on the gradient formed on
the C8-derived base layer. Likewise, the CA hysteresis was approximately 2 times
larger on the C8-modified surfaces, indicative of greater chemical inhomogeneity.
In contrast to uniformly modified substrates, Wilhelmy plate CA analysis that
involves the immersion of samples gave a unique S-shaped CA distance curve for
the gradients. The three curve segments correspond to hydrophilic, hydrophobic,
and a middle connecting region. Importantly, these curves give precise CAs along
the gradient that reflect the surface chemistry and coverage defined by
programmed CRI processing.
PMID- 28421768
TI - Synthesis, Structure, and Properties of Tetrabenzo[7]circulene.
AB - Tetrabenzo[7]circulene, a new member of aromatic saddles, was conveniently
synthesized from 2-(1-naphthoyl)benzoic acid with the seven-membered ring
constructed at an early stage of the synthesis. This method, upon minor
modification, was also useful for synthesis of thiophene-annulated [7]circulenes.
The structures of tetrabenzo[7]circulene and [7]circulene were compared in terms
of symmetry, flexibility, and curvature on the basis of DFT calculations and X
ray crystallography. It was also found that tetrabenzo[7]circulene functioned as
a p-type semiconductor in thin-film transistors and cocrystallized with C60.
PMID- 28421769
TI - X-ray Absorption and Electron Paramagnetic Resonance Guided Discovery of the Cu
Catalyzed Synthesis of Multiaryl-Substituted Furans from Aryl Styrene and Ketones
Using DMSO as the Oxidant.
AB - The first example of DMSO serving not only as a solvent but also as an oxidant to
promote the oxidation of Cu(I) to Cu(II) has been demonstrated. X-ray absorption
and electron paramagnetic resonance evidence revealed a single-electron redox
process where DMSO could oxidize Cu(I) to Cu(II). The novel discovery guided the
rational design of copper-catalyzed oxidative cyclization of aryl ketones with
styrenes to furans, providing a new method for the synthesis of multiaryl
substituted furans from cheap and readily available starting materials.
PMID- 28421770
TI - Selective Synthesis of (E)- and (Z)-Allyl Nitriles via Decarboxylative Reactions
of Alkynyl Carboxylic Acids with Azobis(alkylcarbonitriles).
AB - Allyl nitriles were synthesized from the reactions of arylpropiolic acids with
azobis(alkylcarbonitriles) (AIBN or ACCN). In the presence of Cu(OAc)2 as a
catalyst and pyridine as the solvent, the (E)-stereoisomer was formed as the
major product. This transformation shows good tolerance toward alkoxy, halogen,
alcohol, amine, ester, and ketone functional groups. When the reaction was
conducted with the sterically bulky amine, ethyldiisopropylamine, in the absence
of a copper catalyst, the corresponding (Z)-stereoisomers were formed
preferentially.
PMID- 28421771
TI - Marangoni Contraction of Evaporating Sessile Droplets of Binary Mixtures.
AB - The Marangoni contraction of sessile drops of a binary mixture of a volatile and
a nonvolatile liquid has been investigated experimentally and theoretically. The
origin of the contraction is the locally inhomogeneous evaporation rate of
sessile drops. This leads to surface tension gradients and thus to a Marangoni
flow. Simulations show that the interplay of Marangoni flow, capillary flow,
diffusive transport, and evaporative losses can establish a quasistationary drop
profile with an apparent nonzero contact angle even if both liquid components
individually wet the substrate completely. Experiments with different solvents,
initial mass fractions, and gaseous environments reveal a previously unknown
universal power-law relation between the apparent contact angle and the relative
undersaturation of the ambient atmosphere: thetaapp ~ (RHeq - RH)1/3. This
experimentally observed power law is in quantitative agreement with simulation
results. The exponent can also be inferred from a scaling analysis of the
hydrodynamic-evaporative evolution equations of a binary mixture of liquids with
different volatilities.
PMID- 28421772
TI - Acid-Mediated Intermolecular [3 + 2] Cycloaddition toward Pyrrolo[2,1
a]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G
Trimethyl Ether.
AB - A novel one-pot reaction has been developed for the efficient synthesis of
pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2
nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy
provides a concise total synthesis of the lamellarin core and lamellarin G
trimethyl ether using electrophilic substitution and palladium-catalyzed Suzuki
Miyaura cross-coupling reactions.
PMID- 28421773
TI - Exploring Jolkinol D Derivatives To Overcome Multidrug Resistance in Cancer.
AB - Macrocyclic monoacyl lathyrane derivatives bearing a benzoyl moiety were
previously found to be strong ABCB1 modulators. To explore the effects of
different substituents of the aromatic moiety, 14 new compounds (1.1-1.7, 1.10,
and 2.1-2.4) were prepared from jolkinol D (1), obtained from Euphorbia
piscatoria, and from jolkinodiol (2), its hydrolysis derivative. Compounds 1.8
and 1.9, having aliphatic moieties, were also obtained. The reversal of ABCB1
mediated MDR was evaluated through functional and chemosensitivity assays on the
human ABCB1-gene-transfected L5178Y mouse T-lymphoma cell line. Structure
activity relationships showed that addition of electron-donating groups to the
aromatic moiety improved the activity. The effects on the ATPase activity of the
strongest modulator (1.3) and the inactive jolkinol D (1) were also investigated
and compared. Moreover, in the chemosensitivity assay, most of the compounds
interacted synergistically with doxorubicin. Compounds 1.1-1.10 and 2.1-2.4 were
further assessed for their collateral sensitivity effect against the human cancer
cells: EPG85-257 (gastric) and EPP85-181 (pancreatic), and the matching drug
selected cells EPG85-257RDB, EPG85-257RNOV, EPP85-181RDB, and EPP85-181RNOV. The
most promising ones (1.8 and 1.10) along with compound 3, previously selected,
were investigated as apoptosis inducers. The compounds were able to induce
apoptosis through caspase-3 activation, with significant differences being
observed between the parental and resistant cells.
PMID- 28421774
TI - Cost-effectiveness studies, a necessary tool in clinical nutrition in the XXI
century
PMID- 28421775
TI - Growth charts: which are the appropriate?
PMID- 28421776
TI - Drugs via enteral feeding tubes in inpatients: dispersion analysis and safe use
of dispensers.
AB - OBJECTIVE: This study aimed to improve knowledge about drug administration
through enteral feeding tubes (EFTs) in order to minimize efficacy and safety
problems. MATERIAL AND METHODS: The study was performed in a public secondary
care hospital with level II accreditation by the National Accreditation
Organization (Organizacao Nacional de Acreditacao ONA), in Fortaleza, Ceara,
north-eastern Brazil. RESULTS: One hundred and eight oral solid medications that
could be administered through EFTs and were not available in liquid forms were
evaluated via transformation of their solid dosage forms into liquid forms.
Dispersion times and conditions were assessed to determine which medications
should be crushed. We compared the use of dispensers and syringes and their
connections to enteral feeding tubes and intravenous devices. Medications whose
dispersion occurred within 20 minutes and could be visually perceived and whose
content could be expelled without occluding the oral syringe were considered
"satisfactory". CONCLUSIONS: The dispersion was "satisfactory" in 82 (75.9%) of
the medications; they were classified as capable of being dispersed in water in
the oral syringe for further administration via EFTs without the need for
crushing. Use the dispenser instead of the syringe for drug administration was
safer because the dispenser apparatus did not fit into equipment for intravenous
drug administration.
PMID- 28421777
TI - Quality control of enteral nutrition therapy in cancer patients at nutritional
risk.
AB - INTRODUCTION: Quality indicators in nutritional therapy (QINTs) allow for the
practical assessment of quality in the management of enteral nutrition therapy
(ENT) among hospitalized patients. OBJECTIVE: To control ENT quality in cancer
patients at nutritional risk. METHODS: A prospective, observational study was
performed with cancer patients over 19 years of age who had undergone exclusive
ENT for at least 72 h. Nutritional Risk Screening was used to assess nutritional
risk; in the presence of nutritional risk, the Subjective Global Assessment (SGA)
was used. Six QINTs were applied. RESULTS: Our study included 211 patients (mean
age: 59 +/- 10 years, 67.3% men). Most common cancer diagnoses were head and neck
(68.2%) and gastrointestinal (18%). Nutritional risk was identified in 93.3% (n =
197) of patients; SGA identified malnutrition in 84.2% of patients (n = 166). ENT
was used for 9.7 +/- 7 days, presenting a daily deficit of -243.1 +/- 141 ml of
dietary volume, -363.3 +/- 214.1 kcal, and -14.2 +/- 8.41 g of protein. Three of
the six QINTs were in accordance with the proposed goal: frequency of SGA
application, calculations of nutritional needs, and frequency of diarrhea. Three
of the six QINTs were in disagreement with the proposed goal: ENT infused volume
exceeding 70% of prescribed volume, frequency of digestive fasting exceeding 24
h, and frequency of constipation. Prescriptions for anticholinergic drugs (p =
0.023) and diuretics (p = 0.007) were associated with diarrhea. CONCLUSION:
Nutritional risk and malnutrition are frequent among ENT cancer patients. Quality
control in ENT was moderately impaired by episodes of fasting and intestinal
motility disorders.
PMID- 28421778
TI - Cost analysis of home parenteral nutrition in Spain
AB - Introduction: Home parenteral nutrition (HPN) improves quality of life, allowing
patients to receive nutrition at home and providing a social and labor
integration to these patients.Objective: To assess the direct costs of HPN in
adult population in Spain.Methods: A literature review of the records of HPN in
Spain, carry out by NADYA-SENPE Group (years 2007-2014), was performed. The
analysis included the evolution of: patients requiring HPN, number of
episodes/patient, mean duration of episodes, description of delivery routes and
complications rate. HPN consumption and cost were estimated. Patients were
grouped according to their pathological group: benign and malignant. Direct costs
(?, 2015) included were: parenteral nutrition bags, delivery sets and costs due
to complications.Results: The number of patients who receive HPN has increased
over years (2007: 133 patients; 2014: 220 patients). The average number of
episodes per patient ranged from 1-2 episodes per year. The average duration of
those episodes decreased (2007: 323 days; 2014: 202.8 days). Tunneled catheters
were the most used and septic complications were the most common. The average
annual cost per patient was estimated at ? 8,393.30 and ? 9,261.60 for benign and
malign disease respectively. Considering that 220 patients required HPN in 2014,
an annual cost of ? 1,846.524.96 (? 1,389,910.55 directly due to HPN) and ?
2,037,551.90 (? 1,580,937.50 directly due to HPN) was estimated for patients with
benign and malignant pathologies respectively. Conclusions: These results can be
used to develop future economic evaluations on HPN and to establish effi cient
prioritization strategies to allocate available resources.
PMID- 28421779
TI - Oral glutamine reduces myocardial damage after coronary revascularization under
cardiopulmonary bypass. A randomized clinical trial.
AB - BACKGROUND: Glutamine is the most abundant free amino acid in the body. It
modulates immune cell function and is an important energy substrate for cells in
critically ill patients. Reduction of injury cardiac markers had been observed in
patients receiving intravenous glutamine and in a pilot study with oral
glutamine. The aim of this study was to analyze the effect of preoperative oral
supplementation of glutamine on postoperative serum levels of cardiac injury
markers. METHODS: A randomized clinical trial was performed in 28 Mexican
patients with ischemic heart disease who underwent cardiopulmonary bypass with
extracorporeal circulation. Patients were randomly assigned to receive oral
glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury
markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were
measured at 1, 12, and 24 hours postoperatively. RESULTS: At 12 and 24 hours
serum markers levels were significantly lower in the glutamine group compared
with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001,
respectively). Overall, complications were significantly lower in the glutamine
group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2
cases of multiple organ failure in control group and 1 case of pulmonary embolism
in glutamine group (p = 0.50). CONCLUSION: Preoperative oral glutamine
standardized at a dose of 0.5 g/kg/day in our study group showed a significant
reduction in postoperative myocardial damage. Lower cardiac injury markers
levels, morbidity and mortality were observed in patients receiving glutamine.
PMID- 28421780
TI - Intestinal dysfunction in the critical trauma patients - An early and frequent
event.
AB - BACKGROUND: Small-bowel dysfunction exerts a relevant prognostic impact in the
critically ill patients. Citrullinemia has been used in the evaluation of the
intestinal function and it is considered an objective parameter of the functional
enterocyte mass. Present study proposes to determine the intestinal dysfunction
prevalence and the citrullinemia kinetic profile in severe trauma patients and to
investigate its correlation with severity indicators and clinical outcome.
METHODS: A prospective study including 23 critical trauma patients was performed.
Aminoacidemias were quantified, by ion exchange chromatography, at the admission
and at the first and third days. Severity and outcome parameters were registered.
RESULTS: In severe trauma patients, severe hypocitrullinemia (< 20 MUmol/L)
prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 +/-
11.1 MUmol/L). Baseline citrullinemia was inversely and significantly correlated
with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation
support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 MUmol/L at admission,
observed in 17.4% of patients, was associated with higher shock index (1.27 +/-
0.10 versus 0.75 +/- 0.18, p = 0.0001) and longer duration of invasive
ventilation support (20.3 +/- 7 versus 11.2 +/- 7.1 days, p = 0.029) and
intensive care unit stay (22 +/- 5.9 versus 12.2 +/- 8.8 days, p = 0.048). A
citrullinemia decrease in the first day after admittance superior to 12.7%
constituted a significant predictive factor of in-hospital mortality (75 versus
14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%;
negative predictive value = 85.7%] and lower actuarial survival (69.8 +/- 41.6
versus 278.1 +/- 37.4 days, p = 0.034). CONCLUSIONS: Those results confirm the
high prevalence and the prognostic relevance of hypocitrullinemia, considered a
biomarker of enterocyte dysfunction, in severe trauma patients.
PMID- 28421781
TI - Contribution of bioavailable iron and zinc to the diet of Honduran children under
24 month
AB - Objective: In the present study we analyzed 18 baby food (10 made from
traditional Honduran recipes, and 8 industrial baby food sold in that country)
involving the staple food of Honduran excluded infants breast milk and infant
formulas. Material and methods: The content and bioaccesibility (soluble and
dialysable fractions) of Fe and Zn were determined. For thisin vitro
gastrointestinal digestion in a first phase of gastric digestion (pepsin)
followed by a second phase of intestinal digestion (with pancreatin and bile
salts) was simulated. The atomic absorption spectrometry mineral content measured
in soluble and dialyzable fractions. Results: Traditional porridges from Honduras
(PTH) showed low density of micronutrients being the PTH prepared based on "rice
with beans and greens", "rice with ground beans" and "beans with banana" which
had a higher content values of 1.96, 1.56, and 1.46 mg Fe/100 g, respectively,
although in vitroavailability values below 50% of its content. For Zn in these
recipes, the values found were very low being below the detection limit. In
relation to industrial porridges (PIH), those of "rice", "wheat with milk" and "5
cereals" they had a higher content of Fe (9.4, 8.53 and 7.56 mg Fe/100 g,
respectively). Its availability in vitro was greater than 70% in all cases. PIH
Zn showed values of 1.36, and 0.99 mg Zn/100 g samples of "wheat with milk" and
"wheat with honey", respectively, and increased availability of 75%. Conclusions:
It is shown that PTH have some limitations in its formulation that makes the
selected micronutrients are in fewer and even less bioaccessible, compared with
PIH, so review is recommended to avoid supplementation of these micronutrients
and help improve the nutritional status of the child population as Honduran model
country in Central America.
PMID- 28421782
TI - Breastfeeding for acute pain control on infants: a randomized controlled trial
AB - Objective: To determine the effectiveness of breastfeeding (BF) for the
management in acute pain after vaccination in infants under 6 months of age when
compared to the milk substitute (MS) and not to apply any maneuver. Methods: A
controlled, single-blind phase III clinical trial was conducted on infants under
6 months old to evaluate the effectiveness of BF in acute pain by vaccination.
Divided in 3 groups: BF, milk substitutes (MS), and without applying any
analgesic maneuver (control). Pain was measured by crying time and pediatric pain
scale. Statistical analysis was performed using the Kruskal Wallis and Mann
Whitney U for quantitative variables. For qualitative data, Chi2 was applied
Kaplan Meier was used to analyze the total time crying.Results: A total of 144
patients were recruited, divided in groups of 48 patients. The group of BF had
fewer crying time (p = 0.007) and pain rating at 90 (p = 0.006) and 120 (p =
0.003) seconds compared with other groups. There was no significant difference in
the crying time (p = 0.396) and the pain scale between the group receiving MR and
control.Conclusions: Breastfeeding is effective in management of acute pain by
vaccination in infants under six months of age compared to milk substitute and
control.
PMID- 28421783
TI - Factors associated with body mass index in Brazilian children: structural
equation model
AB - INTRODUCTION: Overweight and obesity in children is an important global problem.
Its prevalence is increasing in developed and developing countries. OBJECTIVE:
The aim of this study was to evaluate the association between socioeconomic
conditions, maternal body mass index (BMI), food security, and intake of
obesogenic foods on excess body weight in children. METHODS: A cross-sectional
study was conducted, using the data of 3,676 children from the latest National
Demographic and Health Survey in Brazil. The children's BMI was the study
outcome. Socioeconomic condition, maternal BMI, food security, and intake of
obesogenic foods were use as predictors. structural equation models were used for
analysis. RESULTS: Socioeconomic conditions directly influenced the children's
BMI (beta = 0.102; p = 0.02), mediated by intake of obesogenic foods (beta =
0.018; p = 0.04). A direct association was observed between maternal and child
BMIs (beta = 0.169; p < 0.001) and intake of obesogenic foods and child BMI (beta
= 0.114; p < 0.001). CONCLUSIONS: Favorable socioeconomic conditions, increased
maternal BMI, and intake of obesogenic foods contributed to increased child BMI.
PMID- 28421784
TI - Assessment of anthropometric indicators in children with cerebral palsy according
to the type of motor dysfunction and reference standard.
AB - AIM: The study aimed to demonstrate that the assessment of the anthropomorphic
measurements of children with cerebral palsy (CP) varies according to the type of
motor dysfunction and references standard used for comparison. METHOD: In a cross
sectional design, 108 children 2 to 16 years were classified according to the
type of motor dysfunction by gender and age group. Weight, mid-upper-arm
circumference (MUAC), and alternative measures for height were performed.
Height/age and weight/age indexes and BMI were evaluated with percentiles and/or
Z-scores with reference to a number of previously published references of growth,
including those of the World Health Organization (WHO). RESULTS: Fifty-three
(49.1%) were females and 55 (50.9%) males. Spastic type was predominant (73.1%)
and 26.9% were other types of dysfunction. Most of the children were located on
level IV (14.6%) and level V (73.1%) of the Gross Motor Function Classification
System (GMFCS). Significant differences were found, suggesting that weight (p =
0.002), height (p = 0.001), and MUAC (p = 0.05) are higher in the spastic group
than in other groups. CONCLUSIONS: The anthropometric indicators were
significantly higher in the spastic group than in other groups. Upper-arm length
(UAL) seemed less appropriate than knee height (KH) and lower-leg length (LLL)
for measuring height. The WHO reference standard was not useful to evaluate the
majority of anthropometric indexes in children with CP, other references as the
growth charts of Day and Brooks have been more suitable.
PMID- 28421785
TI - Association between vitamin D levels and cardiovascular risk factors in obese
children and adolescents.
AB - BACKGROUND AND AIM: Childhood obesity is associated with an increased risk of
chronic disease. We aimed to determine the association between vitamin D
deficiency and cardiovascular risks in obese children. METHOD: The studied
children were selected from obese children who were followed up at obesity
clinic, aged 6-17 years. Basic demographic information and laboratory data were
collected retrospectively from hospital records. RESULTS: A total of 310 students
(178 [57.4%] girls) were evaluated for 25-hydroxyvitamin D (25[OH] D) levels in
late winter/spring. The prevalence rates of vitamin D deficiency, insufficiency,
and sufficiency were 62.3%, 34.5%, and 3.2%, respectively. Insulin resistance was
observed in 146 (47.1%) children; the frequencies of dyslipidemia and
hypertension were 31% and 19.4%, respectively. The mean atherogenic dyslipidemia
ratio was higher in the deficient group (p = 0.049). Inverse correlations of
25(OH) D levels were observed with homeostasis model assessment of insulin
resistance values (r = -0.146, p = 0.010). The mean values of 25(OH) D (ng/mL)
were lower in girls (12.15 +/- 6.60) than in boys (16.48 +/- 8.69) (p < 0.05) and
in children with hypertension (11.92 +/- 5.48) than in those without (14.50 +/-
8.24) (p < 0.05). CONCLUSIONS: Vitamin D deficiency is observed more frequently
than expected in obese children and adolescents. Our findings indicate that low
25(OH) D levels are associated with insulin resistance. Vitamin D deficiency
could contribute to the morbidities associated with childhood obesity, such as
insulin resistance or diabetes mellitus, increased cardiovascular/cardiometabolic
risks, atherogenic dyslipidemia, and hypertension.
PMID- 28421786
TI - Infant growth and early adiposity depending on immigrant background and
anthropometric standards; the CALINA Study.
AB - OBJECTIVE: To compare infant growth and adiposity pattern up to 2 years of age in
Spanish infants, depending on maternal origin and anthropometric standards.
METHODS: Longitudinal study of a representative cohort of infants born at term in
Aragon (Spain) (n = 1.430). Mean z-scores of weight, length, body mass index,
triceps and subscapular skinfolds were calculated until 24 months of age using
World Health Organization (WHO), Euro-Growth and Spanish growth standards and
categorized by maternal origin (Spanish vs. immigrant). RESULTS: Infants of
immigrant mothers had higher weight, length, body mass index, triceps and
subscapular skinfolds than Spanish maternal origin infants during the first
months of life. Mean z-scores significantly varied depending on growth standards
used. At 18 months of age, all anthropometric differences between both groups
disappeared, but only when using WHO growth standards. Mean triceps and
subscapular skinfold z-scores substantially and progressively increased from 3
months to 24 months of age in both groups compared to WHO standards. At 24
months, the prevalence of infants at risk of overweight and overweight were
similar in both groups (Spanish: 15.1% and 3.8%; immigrant: 14.7% and 4.9%,
respectively). CONCLUSIONS: Infant growth, adiposity patterns and prevalence of
overweight depend on maternal origin, showing initial differences which
progressively disappeared at 24 months of life when WHO growth standards were
used. Differences in infant mean anthropometric measurements depend on
anthropometric standard used.
PMID- 28421787
TI - Adherence to the Mediterranean diet pattern, cognitive status and depressive
symptoms in an elderly non-institutionalized population.
AB - INTRODUCTION: Scientific evidence indicates that adherence to the Mediterranean
diet protects against the deterioration of cognitive status and depressive
symptoms during aging. However, few studies have been conducted in elderly non
institutionalized subjects. OBJECTIVE: This study evaluated the relation between
the adherence to the Mediterranean dietary pattern and cognitive status and
depressive symptoms in an elderly population over 75 years. METHODS: A cross
sectional study was conducted in a Mediterranean city (Garrucha, Spain) in 79
elderly people over 75 (36 men and 41 women). Adherence to the Mediterranean
dietary pattern was determined using the Mediterranean Diet Adherence Screener
(MEDAS). Cognitive function was determined by the Mini Mental State Examination
(MMSE), and depressive symptoms were assessed by the Geriatric Depression Scale
(GDS). RESULTS: Most of population showed a very high adherence to the
Mediterranean diet pattern and optimal cognitive and affective status. They
consumed olive oil as their main source of fat, high levels of fish and fruit,
low levels of foods with added sugars, and a low consumption of red meat. A
significant relation between the MEDAS and MMSE scores was found. However, no
relationship was observed between the MEDAS and GDS. CONCLUSIONS: The
Mediterranean diet pattern was positively related with the cognitive function,
although the infl uence of a healthy dietary pattern on the symptomatology of
depression was unclear. However, an effective strategy against cognitive function
and depression would be to improve physical activity rates, establish lifelong
healthy eating habits, and consume a nutritionally-rich diet in order to enhance
quality of life of the elderly.
PMID- 28421788
TI - Factors associated with sarcopenia in institutionalized elderly.
AB - INTRODUCTION: The sarcopenia is a negative aspect for the health of the elderly,
increased the risk for disease and mortality. Additionally can contributes
greatly to functional reducing capacity and quality of life. OBJECTIVE: To
identify the prevalence and factors associated with sarcopenia in
institutionalized elderly. METHODS: This is a cross-sectional study, conducted
with 216 elderly people, aged >= 60 years, of both sexes, residents in long-term
care facilities in Salvador-Bahia, Brazil. To identify sarcopenia was used the
skeletal muscle Index. Covariates were considered: gender, age, time of
institutionalization, type of institution, body mass index and functional
capacity. The Association between sarcopenia and covariates was evaluated using
the Poisson regression model with robust variance. RESULTS: The prevalence of
sarcopenia in the elderly was 72.2% and this condition was associated with male
sex (PR = 1,33; CI 95% = 1,081,65), thinness (PR = 1,29; CI 95% = 1,16-1,43) and
obesity (PR = 0,37; CI 95% = 0,23-0,61). CONCLUSION: The prevalence of sarcopenia
was high among the elderly living in long-term institutions, especially among
men. Elderly with thinness showed greater impairment of muscle reserves, while
the state of obesity was protective.
PMID- 28421789
TI - How does coconut oil affect cognitive performance in alzheimer patients?
AB - Introduction: Alzheimer's disease is one of the most prevalent neurodegenerative
dementia in developed world. This fact, coupled with the lack cure, makes new no
pharmacological therapeutic strategies such as nutrient management to
investigate. In this regard, it stresses the possible influence of coconut oil as
alternative energy source capable of stopping the progressively neuronal death
that occurs in this disease.Objectives: To assess the cognitive impact of coconut
oil in Alzheimer's patients, and specifically in orientation, language-building,
fixing, calculation-concentration and memory areas.Methods: Prospective,
longitudinal, qualitative, analytical and experimental study through a clinical
trial where 44 patients with Alzheimer's in region of Ribera (Valencia), of which
half was selected to receive during 21 days, 40 ml coconut oil daily divided
between breakfast (20 ml) and food (20 ml). Before and after administration of
the oil, they were evaluated through cognitive test Mini-Mental State Examination
to determine possible changes.Results: It was observed in patients who received
coconut oil, that cognitive improvement after completion of the intervention,
statistically significant improved in the orientation and language-construction
areas.Conclusions: Coconut oil appears to improve cognitive abilities of
Alzheimer's patients, with different intensity depending on the cognitive area.
PMID- 28421790
TI - Abdominal obesity is strongly associated to blood pressure in young Mexicans.
AB - OBJECTIVE: The objective of this study was to determine associations between
abdominal obesity (AOb) and the other components of metabolic syndrome (MetS) in
young Mexicans in a cross-sectional survey completed during a 4 year period.
METHODS: This cross-sectional study reports on components and prevalence of MetS
by using Alberti et al. (16) criteria, as well as association between AOb and
elevated blood pressure (BP) of 2,993 Mexican university students, ages 17 to 25
years (66% women) from central and northern Mexico, over a 4-year survey (2010
2013). RESULTS: The most prevalent MetS components in the total sample were low
HDL-C concentration (43.6%) and AOb (41.1%). MetS prevalence was 11.8%, more men
than women were classified with MetS (14.3% vs. 10.5%, p < 0.01). BP was the MetS
component with the lowest prevalence (8.6%). A strong association between AOb and
altered BP with in both men and women was found (OR 4.3, IC95% 2.5-7.4).
CONCLUSIONS: Even BP was the component with the lowest prevalence, AOb was more
strongly associated with it. This fact, could explain the prevalence of
hypertension among young Mexican adults.
PMID- 28421791
TI - Association of 4-hydroxynonenal with classical adipokines and insulin resistance
in a Chinese non-diabetic obese population.
AB - BACKGROUND: The prevalence of obesity is increasing worldwide. Oxidative stress
plays an etiological role in a variety of obesity-related metabolic disorders. 4
hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product
derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse
biological effects that are not well detailed. Obesity is associated with
decreased plasma adiponectin concentrations and increased production of lipid
peroxidation products, including 4-HNE, in adipose tissue. There may be some
association between the level of adipokines and 4-HNE. MATERIAL AND METHODS: To
analyze the associations between 4-HNE and classical adipokines, namely,
adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and
leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects
were determined by ELISA, and their associations with adiposity, glucose, lipid
profiles, insulin secretion and insulin sensitivity were studied. RESULTS: Plasma
4-HNE levels were significantly increased in patients with NDO compared with
healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and
positively correlated with leptin. The plasma levels of 4-HNE were significantly
correlated to several parameters involved in body mass index (BMI) and insulin
resistance (IR). The 4-HNE levels were positively correlated with BMI and
negatively correlated with insulin sensitivity. CONCLUSION: We conclude that 4
HNE is associated with the secretion of adiponectin and leptin and is correlated
with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE
in NDO patients, which supports the potential role of 4-HNE in the development of
obesity-related disorders.
PMID- 28421792
TI - Micronutrient supplementation in gastric bypass surgery: prospective study on
inflammation and iron metabolism in premenopausal women.
AB - BACKGROUND: Low-grade chronic inflammation in morbid obesity is associated with
impaired iron metabolism. Bariatric surgery is effective in weight loss; however,
it can induce specific nutritional deficiencies, such as iron, especially in
premenopausal women. Alternatively, after surgery, there is an improvement in
systemic inflammation, raising questions concerning the dosages of micronutrient
supplementation. OBJECTIVES: This study aimed to assess the effect of two
micronutrient supplementation schemes before and 6 months after a Roux-en-Y
gastric bypass (RYGB) surgery on inflammation and iron metabolism in
premenopausal women. METHODS: This prospective study included 45 premenopausal
women (aged 20-45 years; body mass index [BMI] >= 35 kg/m2) divided into two
supplementation schemes: group 1 (n = 34): daily supplemental dose of 1 RDA 30
days before surgery and 2 RDAs during the six months following surgery; and group
2 (n = 11): daily supplementation of 1 RDA during the 6 months postsurgery.
Anthropometry, dietary intake, inflammation, and iron metabolism were monitored.
RESULTS: Evident reductions in BMI, high-sensitivity C-reactive protein, and
ferritin levels for both groups occurred 6 months after surgery. Additionally,
anemia was 9% in both groups after surgery. However, group 1 exhibited an
increased transferrin saturation index and reduced transferrin levels.
Multivariate regression analysis suggested serum iron, hepcidin, and iron intake
determined ferritin values before and after RYGB surgery. CONCLUSION: Six months
after RYGB, systemic inflammation was reduced in both supplementation schemes.
However, supplementation of 1 RDA before and 2 RDAs after surgery resulted in
better improvements on iron metabolism.
PMID- 28421793
TI - Effects of a high-fat meal on postprandial incretin responses, appetite scores
and ad libitum energy intake in women with obesity.
AB - BACKGROUND: Considering the possible role of triglycerides (TG), glucose
dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in
the regulation of appetite, this study aimed to compare high fat meal-induced
response of GIP and GLP-1, appetite scores and ad libitum energy intake in women
with obesity, according to postprandial increment in triglyceridemia (?TG).
Methods: Thirty-three no-diabetic women (BMI = 35.0 +/- 3.2 kg.m-2) were divided
into two groups: Group with ?TG <= median were called "Low TG change -LTG" and
?TG > median, "High TG change - HTG". Plasma concentrations of GIP, GLP-1 and
appetite sensations were measured prior to, and every 30 min for 180 min after
ingestion of a high-fat breakfast. An ad libitum lunch was served 3 h after the
test meal. RESULTS: The AUC incrementalGIP were significant lower in HTG vs. LTG
group (p = 0.03). The same was observed for GIP levels at 150 min (p = 0.03) and
at 180 min (p < 0.01). Satiety was lower in HTG at 120 min (p = 0.03) and 150 min
(p < 0.01). The AUC totalGLP1 were similar between groups and there were no
between-group differences for the GLP-1 at each time point. Ad libitum food
intake were also similar between groups. CONCLUSIONS: The HTG group exhibited
differences in satiety scores and lower postprandial secretion of GIP, however
with no impact on ad libitum food intake in short term.
PMID- 28421794
TI - Relation of Trp64Arg polymorphism of beta 3 adrenoreceptor gene with metabolic
syndrome and insulin resistance in obese women.
AB - BACKGROUND AND AIM: Trp64Arg variant in beta 3 adrenoreceptor has been reported
to be associated with increased body weight and insulin resistance. These risk
factors are the ones that make up the so-called metabolic syndrome. The aim of
our study was to investigate the relationship between metabolic syndrome and
Trp64Arg polymorphism in the beta3 adrenoreceptor gene in obese women. METHODS: A
population of 531 obese women was analyzed in cross-sectional survey. A
bioimpedance, blood pressure, a serial assessment of nutritional intake with 3
days written food records and biochemical analysis were performed. Genotype of
beta 3 adrenoreceptor gene polymorphism (Trp64Arg) was studied. RESULTS:
Prevalence of metabolic syndrome (MS) with ATP III definition was 47.1% (250
patients) and 52.9% patients without MS (n = 281 patients). Prevalence of beta 3
genotypes was similar in patients with metabolic syndrome (87.6% wild genotype
and 12.4% mutant genotype) and without metabolic syndrome (87.9% wild genotype
and 12.1% mutant genotype). Insulin and HOMA levels were higher in patients with
mutant genotype than wild type, in patients with and without metabolic syndrome.
CONCLUSION: In mutant group of beta3 adrenoreceptor gene patients have higher
insulin and HOMA levels than wild type group, without relation with metabolic
syndrome.
PMID- 28421795
TI - BMI, BMIfat, BAI or BAIFels - Which is the best adiposity index for the detection
of excess weight?
AB - OBJECTIVE: To compare the diagnostic performance of adiposity indeces body mass
index (BMI), body mass index adjusted for fat mass (BMIfat), body adiposity index
(BAI) and body adiposity index for the Fels Longitudinal Study sample (BAIFels)
and the overweight detection in a sample of the Brazilian population. METHODS:
Cross-sectional study with 501 individuals (female/male = 387/114), which
underwent anthropometric measurements and body composition for subsequent
calculation of adiposity indices. Statistical analyzes considered p < 0.05 as
statistically significant. RESULTS: The averages were: age of 46.94 +/- 14.22
years and 48.05 +/- 14.40 years, weight 79.5 +/- 16, 14 kg and 70.42 +/- 16,62
kg, height 172.86 +/- 7.6 cm and 159.0 +/- 7,35 cm, for men and women,
respectively. According to the eutrophic ratings and overweight, the BMIfat
ranked 40.3% and 34.0% for men and 21.7% and 65.0% for females, r espectively.
While the BAI held 47.7% and 62.3% for men and 65.6% and 34.4% for women,
respectively. The receiver operating characteristic (ROC) curve of BMIfat was
clearly superior to all other indexes for both men (93.1%) and women (97.8%),
respectively. CONCLUSION: Findings suggest that BMIfat is the index that has
better relationship with the prediction of body fat, BAI did not exceed the
limitations of BMI. Future studies should seek to expand this study by adopting
the gold standard methods such as DXA and it is necessary to extend the
investigation of the validity of adiposity indices to different ethnic groups.
PMID- 28421796
TI - Effect of satiety on body composition and anxiety in university athletes: cohort
study.
AB - BACKGROUND: Satiety is a determining parameter in nutrient intake control, which
in the long run impacts on body weight. Many athletes need strict control on
their weight to achieve their aims of the season. AIM: The aim of this study is
to analyse the influence of satiety on body weight control and competitive
anxiety in a university athletes population when they ingest ad libitum foods
(SATIETY), or follow a nutritional dietary programme (DIET). METHODS: The present
study was a cohort study, in which 40 male university athletes participated. The
assessment of body weight was done using the ISAK recommendations in its limited
profile. The study of competitive anxiety was evaluated using the CSAI-2
questionnaire. RESULTS: Results showed that the DIET group decreased
significantly their body weight compared to the SATIETY group, they also obtained
a significant improvement in their body composition, reducing fat mass. The
SATIETY group didn't show significant reductions in fat mass. This group showed
higher competitive anxiety values than the DIET group. CONCLUSIONS: The
university athletes that follow an adapted and individualized diet seem to show
improvements in their body composition and anxiety compared to those with ad
libitum food.
PMID- 28421797
TI - Malnutrition in hospitalized patients: results from La Rioja.
AB - BACKGROUND: There is a high malnutrition prevalence in hospitalized patients.
AIM: To determine the malnutrition prevalence in hospitalized patients of La
Rioja Community (Spain) when evaluated with different screening/ evaluation tools
and its relationship with hospital stay and mortality. METHODS: Cross sectional
observational study of hospitalized adult patients (age > 18 years old) from
medical and surgical departments that underwent within 72 h of their admission a
nutritional screening with Malnutrition Universal Screening Tool (MUST),
Nutritional Risk Screening (NRS) 2002, Controlling Nutritional Status (CONUT) y
Subjective Global Assessment (SGA). RESULTS: 384 patients (273 medical and 111
surgical) were evaluated. Almost fifty percent of them were considered
malnourished independently of the screening/assessment tool used. High
concordance was found between SGA and NRS-2002 (k = 0.758). Malnourished patients
had a longer hospital stay than those well-nourished (9.29 vs. 7.10 days; p =
0.002), used a greater number of medicines (9.2 vs. 7.4; p = 0.001) and underwent
a higher number of diagnostic tests (16.4 vs. 12.5; p = 0,002). CONCLUSIONS: Half
of the hospitalized patients in the medical and surgical department of La Rioja
are malnourished. This is associated with a longer hospital stay, higher use of
medicines, diagnostics tests and greater mortality. Malnutrition could be
detected with easy screening tools to treat it appropriately.
PMID- 28421798
TI - Assessment of individual carotenoid and vitamin A dietary intake in overweight
and obese Dominican subjects.
AB - INTRODUCTION: Carotenoids are plant pigment with important biological activities
in humans, such as provitamin-A among others. At present, there are no individual
carotenoid intake data in the Dominican population, which is at risk of vitamin A
deficiency and has an important percentage of overweight and obese individuals .
OBJECTIVE: To assess the individual components of vitamin A intake (retinol,
alpha-carotene, beta-carotene and beta-cryptoxanthin) and that of other relevant
dietary carotenoids like lutein, zeaxanthin and lycopene of Dominican daily food
intake. METHODS: Fifty overweigth and obese subjects (22-69 y). Individual
carotenoid intake, from whole diet and from the ingestion of fruits and
vegetables, was determined using three 24 h diet recalls and a specific
carotenoid database. Retinol, macronutrient and energy intake were calculated
using DIAL(r) software. RESULTS: The total carotenoid intake was 6363.2 ug/day,
56. 1% corresponding to provitamin A carotenoids (74.3% beta-carotene). Vitamin A
intake was supplied by retinol (40%) and by provitamin A carotenoids (60%);
vegetables contributed more than fruits (39.2% and 19.2%, respectively). Non
provitamin A carotenoid intake represents 43.9% of the total intake and is
supplied by lycopene and lutein plus zeaxanthin in similar percentages (52.3% and
47.7%, respectively). CONCLUSIONS: The diet of these Dominican subjets met the
recommended vitamin A intake, when expressed as retinol equivalents, 59% of which
was supplied by provitamin-A carotenoids from plant sources, mainly by red/orange
and white/yellow foods. Individual carotenoid intake is an aspect of great
interest for issuing dietary recommendations in the public health setting.
PMID- 28421799
TI - Antihypertensive effect of fermented skim camel (Camelus dromedarius) milk on
spontaneously hypertensive rats.
AB - BACKGROUND: Hypertension is one of the most common diseases in worldwide, thus
prevention of hypertension is important in reducing the risks of cardiovascular
disease. Milk contains bioactive peptides released during milk fermentation which
lead to exhibit angiotensin I converting enzyme (ACE) inhibitory. OBJECTIVE: The
aim of this study was to investigate the antihypertensive effect of fermented
skim camel milk on rats and compared with unfermented skim camel milk as control.
METHODS: The antihypertensive effect of fermented skim camel milk on thirty six
male spontaneously hypertensive rats (SHR) was carried out for (short-term) and
(long-term) using different doses (80, 240 and 1200 mg/kg body weight).
Angiotensin converting enzyme (ACE) activity was also measured using ACE Kit.
RESULTS: The blood pressure (systolic and diastolic) of spontaneously
hypertensive rats (SHR) in short term administration (24 hours) of 1200 mg/kg
body weight fermented skim camel milk decreased significantly (p < 0.05) from 22
to 36 mmHg and 28 to 32 mmHg, respectively, at four and eight hour of post
administration. On the other hand, the blood pressure of fermented skim camel
milk for long-term (20 days) decreased and affected the heart rate (beats/min).
The lowest record of systolic (41 mmHg) and diastolic blood pressure (19 mmHg)
were at dose of 1200 mg/kg body weight of fermented skim camel milk at 15 days of
administration. Likewise, ACE activity in plasma of SHR administered fermented
skim camel milk decreased significantly (p < 0.05) compared with the control
group. CONCLUSION: The hypotensive effect of fermented skim camel milk by L.
helveticus and S. thermophillus in SHR rats depends on the high dose of fermented
skim camel milk in short and long-term. The ACE activity inhibitory was clear
with fermented skim camel milk.
PMID- 28421800
TI - Prevalence and associated factors of sugar-sweetened beverages intake among
schoolchildren aged 9 to 17 years from Bogota, Colombia: the FUPRECOL Study
AB - Objective: The aim of the present study was to describe the intake of sugar
sweetened beverages and to examine of associated factors among schoolchildren
from Bogota, Colombia.Methods: From a total of 8,136 schoolchildren and
adolescents (age 9-17.9 years) taking part in the FUPRECOL Study. Sugar-sweetened
beverages intake was based on intake from "regular soda", "drink tea" and/or
"concentrated juices". Body weigth, heigth, body mass index (BMI), waist
circumference, and percentage body fat by electrical bioimpedance analysis were
measured such as adiposity markers. Associated factors (sex, age, abdominal
obesity, BMI classification, mothers' and fathers' educational level and
nutritional status by "Krece plus" questionnaire), were collected by structured
questionnaire. Associations were established through a binary logistic
regression. Results: Of the subjects, 58.4% were women. According to sex, boys
response highest intake of "regular soda" daily/weekly frequency of the 70.9% and
21.0%, respectively, followed by "concentrated juices" (64.4% weekly vs.11.3%
daily). In both gender, the prevalence of abdominal obesity was higher in
schoolchildren that responded to intake "regular soda" (23.3%), "concentrated
juices" (13.2%) and "drink tea" daily (9.7%). Age [OR 1.15 (95%CI 1.03 to 1.28)],
mothers' [OR 1.30 (95%CI 1.03 to 1.65)], and fathers' [OR 1.34 (95%CI 1.01 to
1.79) low educational level and nutritional status [OR 2.60 (95%CI 2.09 to
3.25)], were associated with daily intake of "regular soda".Conclusion: Age,
parental education level and dietary patterns were associated with sugar
sweetened beverages in schoolchildren in Bogota, Colombia. We recommended
comprehensive interventions which are involved nutritional and educational
component among children and adolescents from Bogota, Colombia.
PMID- 28421801
TI - Attitudes of Chilean students from different socioeconomic levels at the
beginning of the implementation of the law governing the sale and advertising of
foods high in critical nutrients
AB - Background: On June 27th 2016 the law that regulates sale and advertising of
foods high in critical nutrients was implemented in Chile. This law regulates the
processed food packaging labelling of foods high in calories, saturated fats,
sugars and sodium.Objective: To determine 8-12 year old school children
attitudes, from different socioeconomic levels (SEL) and nutritional status,
toward the new food labelling law.Methods: A previously validated survey was
applied, adding questions regarding the new logos to be added on the packaging of
foods and beverages. A descriptive analysis of the variables being studied was
conducted and differences in relation to the SEL and nutritional status were
determined using the Chi2 test.Results: Statistically significant differences
were not observed for gender or city. Regarding the new logos, 87.3% of the
children from a medium to high SEL and 78.5% from low SEL indicated that they
liked to be informed about the contents of food (p < 0.01). Fifty-three per cent
from medium to high SEL and 48% from low SEL would stop buying the foods with
logos. Fourteen per cent to 22% will continue to consume sweet biscuits, sugary
drinks, chocolates and chips, without a difference in SEL. Children with a normal
nutritional status and medium to high SEL placed more importance on logos high in
calories, saturated fats and sodium, and children of low SEL on logos high in
sugar. Overweight or obese children from medium to high SEL considered all four
logos more important than children of low SEL.Discussion: These results will
facilitate educational and social marketing support to improve the understanding,
compliance and fulfillment of the law.
PMID- 28421802
TI - Psychological capital and its relationship with lifestyle of Mexican university
students
AB - Background: University students don't have a healthy lifestyle so it is necessary
to identify psychosocial variables that can increase it.Objective: To determine
the relationship between the psychological capital (CapPsi) and lifestyle (EV) of
Mexican university students.Method: A cross-sectional and correlational study was
carried out among 320 students of a public university. The sample was non
probabilistic by quotas. To assess the factors of CapPsi were used the General
Scale of Self-efficacy, the Scale of Hope for Adults, Questionnaire of
Resilience, the Life Orientation Test and; to assess the lifestyle was used the
Fantastic questionnaire.Results: The variables of the CapPsi correlated with the
healthy lifestyle; resilience (r = 0.505, p < 0.01); hope (r = 0.432, p < 0.01);
optimism (r = 0.412, p < 0.01); and self-efficacy (r = 0.400, p < 0.01). The 33.3
of the total variance of the lifestyle was explained by the CapPsi (R2 =
0.333).Conclusions: Based on the results, it is assumed that the CapPsi improve
lifestyle; however, further research is necessary to determine if the influence
of CapPsi is in the adoption and / or maintenance of healthy lifestyle and
identify how each one of its factors infl uences it particularly. The CapPsi has
a representative percentage of prediction of healthy lifestyle. It is necessary
that health promotion and prevention programs incorporate the approach of CapPsi
to achieve a healthy lifestyle in the university students.
PMID- 28421803
TI - Risk factors related with lifestyle in patients with musculoskeletal disorders
AB - Background: Musculoskeletal disorders (MSDs) encompass a series of debilitating
diseases with high incidence and prevalence, representing a high economic and
social cost. Prevention is crucial, so is of great interest to determine
modifiable risk factors, such as those related to lifestyle. Methods: A
descriptive cross-sectional study was performed in 91 patients selected by
systematic random sampling and were divided into three experimental groups
according to the cause and evolution of its MSD (neck pain, knee pain and back
pain). A biometric measurement, nutritional assessment, physical and occupational
activity, muscle balance and oxidative status was performed.Results: The female
is the most affected gender by the presence of musculoskeletal injuries such as
neck pain and back pain. Overall, most patients (67.4%) had normal weight,
overweight 24.41% and only 8.1% were obese type I. Patients with neck pain are
the group doing less physical activity and worse muscular balance present.
Oxidative stress was higher in patients with knee pain than in the other groups.
Regarding the consumed diet, differences between experimental groups on the
mineral content (Zn, Mn, Se and I) and vitamins (folate and ascorbic acid) are
observed. Conclusions: Cholecalciferol intake and vitamins A and D is less than
those recommended in all subjects, which promotes muscle disease. Folate intake
was below recommendations, increasing susceptibility to oxidative stress. Obesity
and oxidative stress related to the prevalence of the different types of MSDs
studied.
PMID- 28421804
TI - Composition and diversity of acaroids mites (Acari: Astigmata) community in the
stored rhizomatic traditional Chinese medicinal materials.
AB - OBJECTIVE: To investigate the species and breeding density of ac a roid mites in
the stored rhizomatic traditional Chinese medicinal materials in Anhui province,
China, in order to supply evidences for control and prevention of such species.
METHODS: The stored traditional Chinese medicinal materials of root-stock origins
were collected in 30 herb stores and warehouses in 17 cities across Anhui
province. Mites were collected by using Tullgren funnel and directicopy, and
identified under microscopy. RESULTS: Twenty-two species of acaroid mites,
belonging to 15 genera under 5 families, were identified from the total 47 stored
samples, in which Tyrophagus putrescentiae, Acarus farinae, Carpoglyphus lactis,
and Cologlyplus berlesei were predominant. CONCLUSION: Breeding density of
acaroid mites was high in the stored rhizomatic traditional Chinese medicinal
materials in Anhui province. This indicates that the traditional Chinese
medicinal herbs of root-stock origins in storage are seriously contaminated by
the acaroid mites, and such infestation should be positively controlled to reduce
the potential harm to public health.
PMID- 28421805
TI - Trematode Aspidogastrea found in the freshwater mussels in the Yangtze River
basin.
AB - OBJECTIVE: To investigate the prevalence of trematode Aspidogastrea in the
freshwater mussels in the Yangtze River basin within Anhui province, China.
METHODS: We initially harvested the freshwater mussels living in the Yangtze
River running through Anhui area, and labeled them with corresponding number.
Then the samples were dissected for isolating the flukes, which were identified
by conventional staining. RESULTS: Infection rate of trematode Aspidogastrea in
freshwater mussels in the Yangtze River basin within the territory of Anhui
province was 30.38% (103/339) in general, and a total of 912 flukes of
Aspidogastrea were detected in the 103 mussels, with average infection rate of
8.85 for each mussel. CONCLUSION: Trematode Aspidogastrea is prevalent in the
freshwater bivalves living in the Yangtze River basin running through Anhui area,
and the treamatode was identified as Aspidogaster sp. belong to Aspidogaste under
Aspidogastridae of Aspidogastrea.
PMID- 28421806
TI - Diet and liver apoptosis in rats: a particular metabolic pathway.
AB - INTRODUCTION: Various studies have indicated an association between modifi cation
in dietary macronutrient composition and liver apoptosis. OBJECTIVE: To explain
how changes in metabolic pathways associated with a high-protein, high-fat, and
low-carbohydrate diet causes liver apoptosis. METHODS: Two groups of rats were
compared. An experimental diet group (n = 8) using a high-protein (59.46%), high
fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with
American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after
eight weeks, the adipose tissue weighed, the liver removed for flow cytometry
analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF,
triglycerides, malondialdehyde, and beta-hydroxybutyrate. Statistical analysis
was carried out using the unpaired and parametric Student's t-test and Pearson's
correlation coeffi ents. Significance was set at p < 0.05. RESULTS: Animals from
the experimental group presented less adipose tissue than dose of the control
group. Percentage of nonviable hepatocytes in the experimental group was 2.18
times larger than the control group (p = 0.001). No statistically significant
differences were found in capillary glucose, insulin, glucagon, IL-6, or TNF
alpha between two groups. Plasmatic beta-hydroxybutyrate and malondialdehyde of
the experimental group expressed higher levels and triglycerides lower levels
compared with the control group. The results show a positive and significant
correlation between the percentage of nonviable hepatocytes and malondialdehyde
levels (p = 0.0217) and a statistically significant negative correlation with
triglycerides levels (p = 0.006). CONCLUSION: Results suggest that plasmatic
malondialdehyde and triglyceride levels are probably good predictors of liver
damage associated with an experimental low-carbohydrate diet in rats.
PMID- 28421807
TI - The antioxidants in the process of ocular pathology
AB - Introduction: The influence of antioxidants on ocular processes has taken on a
significant importance in recent years for its effects on visual health.
Oxidative stress is a factor involved in the development of major pathologies
such as cataracts, glaucoma and age-related macular degeneration (AMD).Objective:
To establish the scientific evidence that exists about the different types of
antioxidants and their effects on ocular pathological processes through a
systematic review.Methods: Literature search in MEDLINE, Scielo and Cochrane for
studies evaluating the use of antioxidants in the prevention and/or treatment of
eye diseases. Selected randomized controlled clinical trials over the past 7
years were selected.Results: The relationship between different types of
antioxidants, vitamin E, C, beta carotene, zinc, lutein, anthocyanins and
carotenoids, suggests a positive relationship with the risk and progression of
AMD and glaucoma parameters, indicating a lower risk of the disease due to an
increased consumption of antioxidants in the diet. Initial reports suggest a
potential role for diet modification in the treatment of age-related macular
degeneration and glaucoma primarily, not evidencing for the prevention of
cataract.Conclusions: Promoting adequate consumption of antioxidants in the diet
can prevent and protect against highly prevalent eye diseases. The antioxidants
of the group of vitamins are the most studied so far in the ocular pathologies.
More clinical trials are needed to establish these relationships more precisely.
PMID- 28421808
TI - Body-image dissatisfaction in children and adolescents: a systematic review
AB - Background: The difference in the perception between the perceived silhouette and
the desired silhouette has been defined as body image dissatisfaction
(BID).Objective: To review the type of methods for measuring BID, the frequency
of BID among children and adolescents.Method: We searched studies through
electronic databases (PubMed, Scielo and EBSCOhost), from cross-sectional studies
published in English or Spanish. Eligible studies assessing BID in children and
adolescents published in Spanish and English, from April 2010 to April 2015. Age,
sex, weight and method or scale used to evaluate the BID and the self- perception
of body weight were assessed.Results: Sixteen studies met the inclusion criteria,
and included children and adolescents aged 5 to 19 years. Nine types of
measurement methods of BID were found. In most of the studies, temporal stability
and validity test were performed. In BID studies where frequency was reported,
ranged from 44% to 83% for overweight or obese and 1.7% a 37% for underweight. In
some studies, BID was associated with age and was more frequent among girls. BID
was also present in thin boys.Conclusion: BID was more frequent among girls and
was positively associated with BMI. Despite the variety of methods used, the
results are consistent.
PMID- 28421809
TI - Recommended energy and nutrients intakes in the European Union: 2008-2016
AB - The aim of this document is to refl ect the changes happened in the European
Union legislation and the opinions of the European Food Safety Authority in
relation to the nutritional labeling on food, the reference values for energy,
macronutrients and micronutrients, and the tolerable upper safe levels.The
European legislation in force uses the labeling reference values established by
the Scientific Committee on Food in 2003. There would be advisable an update of
them from the reference values for vitamins and minerals established by the
European Food Safety Authority. Equally, there would be good to include reference
labeling values for polyunsaturated fatty acids, dietary fiber and choline, and
specific reference labeling values for children from 6 to 36 months.For vitamins
and minerals there would be desirable the revision of tolerable upper safe levels
and the establishment of maximum amounts allowed in fortified food and food
supplements in the European Union; its absence might represent a risk in some
population groups for an excessive and unsafe intake of certain minerals and
vitamins.
PMID- 28421810
TI - Catheter traction and gastric outlet obstruction: a repeated complication of
using a Foley catheter for gastrostomy tube replacement.
AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a safe procedure and
major morbidity is unusual. However, the number of PEG fed patients is increasing
all over the world and complications may become more and more frequent. CASE
REPORT: We describe a 73 years old woman with persistent vomit after replacement
of the standard PEG tube with a Foley catheter. An upper GI endoscopy showed the
catheter pulled into the duodenum causing gastric outlet obstruction. It was
removed and replaced by a suitable standard PEG tube, allowing PEG feeding to be
resumed. DISCUSSION: Previous reports pointed the risk of this complication,
almost always associated with insertion of a Foley-type catheter. Replacement of
PEG tubes should be performed by experienced teams using standard PEG tubes and
the use of Foley-type catheters for this purpose should be banned from routine
practice.
PMID- 28421811
TI - Characterization of Ornithobacterium rhinotracheale field isolates from Hungary.
AB - Ornithobacterium rhinotracheale is a widely distributed rod-shaped Gram-negative
bacterium that infects several avian species including chickens and turkeys. It
is associated with respiratory signs, growth retardation, mortality, and reduced
egg production, thus causing severe economic losses to the poultry industries. In
this study, 37 field isolates of O. rhinotracheale, collected from various
locations in Hungary between 1997 and 2015, were identified and characterized by
the analysis of partial 16S rRNA gene sequences, enterobacterial repetitive
intergenic consensus (ERIC)-PCR, and random amplified polymorphic DNA (RAPD) PCR
assays with the OPG11, OPH19, and M13 primers. Most of the field isolates were
serotype A, one was serotype B, and four were serotype D. One isolate could not
be typed with antisera against serotypes A-E. In a phylogenetic analysis of the
16S rRNA sequences, the isolates formed two clusters. Thirteen distinct patterns
were identified with ERIC-PCR, and the RAPD assay with the M13 primer assigned
the isolates to 10 different patterns. The other two RAPD assays were unsuitable
for distinguishing and grouping the isolates. Neither ERIC type nor RAPD pattern
correlated with the place or year of isolation. However, the strains isolated
from chickens were more heterogeneous on ERIC-PCR than the isolates recovered
from turkeys. In this study, ERIC-PCR was the most discriminatory method for
investigating the genetic diversity of O. rhinotracheale isolates.
PMID- 28421812
TI - Frequency of Incidental Findings and Subsequent Evaluation in Low-Dose Computed
Tomographic Scans for Lung Cancer Screening.
AB - RATIONALE: The U.S. Preventive Services Task Force recommends lung cancer
screening with low-dose chest computed tomographic scans (LDCT) for a well
defined high-risk population. Data on the frequency and impact of incidental
findings (IFs) based on LDCT scans performed within a centralized lung cancer
screening program have not been reported. OBJECTIVES: Researchers in previous
studies have reported IFs in the setting of clinical trials. We present our
findings in a real clinical setting where the decision to manage these findings
may depend on factors that are not captured in a research trial such as
disclosing IFs, patient preferences, severity of comorbidities, and physician
expertise. METHODS: We conducted a retrospective chart review of participants in
the Cleveland Clinic Lung Cancer Screening Program from April 1, 2015, to
February 17, 2016. Lung Imaging Reporting and Data System categories and all
reported findings were extracted from the structured radiology report. Downstream
investigations that occurred as a result of the imaging findings were recorded.
Medicare reimbursement rates were documented for all screening-related testing
and treatment. RESULTS: A total of 320 LDCT-screened patients' records were
reviewed. The most commonly reported IFs were pulmonary (69.6%), cardiovascular
(67.5%), and gastrointestinal (25.9%). Fifteen percent of the scans had an IF
that resulted in further evaluation. The majority of patients who underwent
further testing had cardiovascular findings (10.3%); less frequently, they had
thyroid or adrenal nodules (2.1%), hepatic lesions (0.9%), renal masses (0.6%),
or pulmonary disease (0.6%). The most frequently ordered investigations were
echocardiography (n = 9), cardiac stress test (n = 9), and CT angiography (n =
6). Reimbursement for the screening process, evaluation, and treatment of
screening-detected findings averaged $817 per screened patient. CONCLUSIONS:
Clinically significant IFs on LDCT scans for lung cancer screening are common,
and their potential impact should be included in the shared decision-making
process. Screening program staff should develop a standard approach for the
evaluation of these findings and consider the financial impact when seeking
infrastructure support for screening program implementation.
PMID- 28421814
TI - Elevated Monocyte to High-Density Lipoprotein Cholesterol Ratio and Endothelial
Dysfunction in Behcet Disease.
AB - Behcet disease (BD) is a multisystemic disorder characterized by endothelial
dysfunction and inflammation. Monocyte to high-density lipoprotein cholesterol
ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress.
Sixty patients with BD and 50 control individuals were included to investigate
the relationship between MHR and endothelial dysfunction. Endothelial function
was assessed by flow- and nitroglycerin-mediated dilatation technique (FMD and
NMD, respectively). Serum high-sensitivity C-reactive protein (hsCRP) levels were
measured in all study participants. The MHR and hsCRP levels were significantly
higher in patients with active BD than in controls. Brachial artery FMD was
significantly lower in patients with active BD than in controls. Brachial artery
NMD was similar between groups. There was a strong inverse correlation between
MHR and FMD and a strong positive correlation between MHR and serum hsCRP levels.
Thus, elevated MHR may be a useful marker reflecting impaired endothelial
function and systemic inflammation in patients with BD.
PMID- 28421813
TI - Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic
Cell Death.
AB - Hemin, the oxidized prosthetic moiety of hemoglobin, has been implicated in the
pathogenesis of acute chest syndrome in patients with sickle cell disease by
virtue of its endothelial-activating properties. In this study, we examined
whether hemin can cause lung microvascular endothelial barrier dysfunction. By
assessing transendothelial resistance using electrical cell impedance sensing,
and by directly measuring trans-monolayer fluorescein isothiocyanate-dextran
flux, we found that hemin does cause endothelial barrier dysfunction in a
concentration-dependent manner. Pretreatment with either a Toll-like receptor 4
inhibitor, TAK-242, or an antioxidant, N-acetylcysteine, abrogated this effect.
Increased monolayer permeability was found to be associated with programmed cell
death by necroptosis, as evidenced by Trypan blue staining, terminal
deoxynucleotidyl transferase dUTP nick-end labeling assay, Western blotting for
activated forms of key effectors of cell death pathways, and studies utilizing
specific inhibitors of necroptosis and apoptosis. Further studies examining the
role of endothelial cell necroptosis in promoting noncardiogenic pulmonary edema
during acute chest syndrome are warranted and may open a new avenue of potential
treatments for this devastating disease.
PMID- 28421815
TI - Cross-protection conferred by immunization with an rOmpH-based intranasal fowl
cholera vaccine.
AB - A previous study demonstrated that a recombinant outer membrane protein H (rOmpH)
based intranasal fowl cholera vaccine elicited efficient homologous protection
against the Pasteurella multocida strain X-73 (A:1) in chickens. The present
study aimed to determine the cross-protectivity against heterologous P. multocida
strains. The rOmpH was purified via electroelution and formulated with two kinds
of adjuvants. The vaccine formulations in a total volume of 100 ul were 100 ug
rOmpH with 3 ug of Escherichia coli enterotoxin B or 10 ug of CpG ODN2007.
Chickens were assigned to three experimental groups depending on bacterial strain
challenge exposure as well as three control groups. The chickens were immunized
intranasally three times at three-week intervals. Challenge exposures were
conducted by inoculation with homologous strain X-73 or heterologous strains P
1059 (A:3) or P-1662 (A:4) at four weeks after the final immunization. The
specific antibody against rOmpH was produced in vaccinated birds. Sera IgY and
secretory IgA antibody titres were significantly increased (P < 0.05) post
immunization. The stimulation index values of the vaccinated groups were
significantly different from stimulation index values of the non-vaccinated
groups (P < 0.05). Chicken survival rates after exposure to avian P. multocida
strains ranged from 70% to 100%. There was no significant difference in
protection between two kinds of adjuvants in vaccine formulations. Statistical
analysis indicated no significant differences in protection among avian P.
multocida strains challenge exposure. We conclude that an in-house rOmpH-based
intranasal fowl cholera vaccine produced efficient cross-protectivity against
heterologous strains of P. multocida.
PMID- 28421816
TI - Cytotoxic steroid derivatives from the Vietnamese soft coral Sinularia brassica.
AB - Using various chromatographic separations, six ergostane-type steroids, including
one new compound sinubrassione (1), and two pregnene-type steroid glycosides,
including one new compound sinubrassioside (7), were isolated from methanol
extract of the Vietnamese soft coral Sinularia brassica. The structure
elucidation was confirmed by spectroscopic methods including 1D, 2D NMR and HR
ESI-MS. The cytotoxic activities of all the isolated compounds against three
human cancer cell lines were also evaluated using MTT-based colorimetric assays.
PMID- 28421817
TI - Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after
Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five
Intractable Cases.
AB - Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized
by the excessive accumulation of surfactant proteins within the alveolar spaces
and by higher titers of autoantibodies to granulocyte-macrophage colony
stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The
antibodies inhibit the maturation and phagocytosis of alveolar macrophages.
Although the standard therapy for aPAP has been whole-lung lavage (WLL), this
procedure is invasive and needs to be repeated for several years. GM-CSF
inhalation therapy is a new procedure for treating aPAP and can induce remission
with less invasiveness, although it is generally less effective in severe cases.
We evaluated five cases with remarkable improvement by using sequential GM-CSF
inhalation therapy after WLL; however, the treatment failed when this therapy
preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the
efficiency of WLL in patients with severe aPAP.
PMID- 28421818
TI - Cell Origin Dictates Programming of Resident versus Recruited Macrophages during
Acute Lung Injury.
AB - Two populations of alveolar macrophages (AMs) coexist in the inflamed lung:
resident AMs that arise during embryogenesis, and recruited AMs that originate
postnatally from circulating monocytes. The objective of this study was to
determine whether origin or environment dictates the transcriptional, metabolic,
and functional programming of these two ontologically distinct populations over
the time course of acute inflammation. RNA sequencing demonstrated marked
transcriptional differences between resident and recruited AMs affecting three
main areas: proliferation, inflammatory signaling, and metabolism. Functional
assays and metabolomic studies confirmed these differences and demonstrated that
resident AMs proliferate locally and are governed by increased tricarboxylic acid
cycle and amino acid metabolism. Conversely, recruited AMs produce inflammatory
cytokines in association with increased glycolytic and arginine metabolism.
Collectively, the data show that even though they coexist in the same
environment, inflammatory macrophage subsets have distinct immunometabolic
programs and perform specialized functions during inflammation that are
associated with their cellular origin.
PMID- 28421820
TI - Characteristics associated with physical activity capacity and performance in
children and adolescents with an acquired brain injury.
AB - AIM: To examine characteristics associated with physical activity capacity and
performance in children with acquired brain injury (ABI). METHODS: 58 children
(32 men; age 11 years 11 months +/- 2 years 6 months; Gross motor function
classification system [GMFCS] equivalent I = 29, II = 29) >12 months post ABI
were recruited. Physical activity capacity measures included: (i) combined score
of three 30-second repetition maximum functional strength exercises; (ii) timed
up and go; (iii) 6-minute walk test and (iv) high-level mobility assessment tool
(HiMAT). Physical activity performance determined time spent in sedentary, light
and moderate to vigorous physical activity (MVPA). Full scale intelligence
quotient (FSIQ) was assessed using the Wechsler intelligence scale for Children
IV. Regression models were constructed with functional strength score (n = 56),
activity counts/minutes and time spent in MVPA and sedentary (n = 37). RESULTS:
The HiMAT and FSIQ explained 69% of the variance in functional strength. Age
explained 12% of the variance in counts/min and 14% of the variance in time spent
sedentary. GMFCS explained 10% of the variance in time spent in MVPA.
CONCLUSIONS: The ability to perform functional strength exercises is associated
with mobility beyond independence and adequate intellectual ability for children
with ABI. Age was the most significant factor associated with physical activity
performance, and interventions should target adolescents with ABI.
PMID- 28421819
TI - IL-4 Induces IL17Rb Gene Transcription in Monocytic Cells with Coordinate
Autocrine IL-25 Signaling.
AB - IL-25 and IL-4 signaling in the setting of infection or allergic responses can
drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to
mediate signaling through nuclear factor kappa B (NF-kappaB) transcriptional
activation. Despite the known coexistence of these two cytokines in the Type 2
inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes
is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb
protein in human lung tissue culture, primary alveolar macrophages, and the THP-1
monocytic cell line. IL-4 treatment triggers gene transcription for both IL-25
and IL-17Rb but does not alter the receptor mRNA stability. Genetic antagonism of
the IL-4 second messenger, signal transducer and activator of transcription 6
(STAT6), with small interfering RNA (siRNA) blunts IL-17Rb mRNA induction by IL
4. IL-25 induces signaling through the canonical NF-kappaB pathway, and STAT6 or
NF-kappaB signaling inhibitors prevent IL-17Rb expression. Blockade of IL-25 with
monoclonal antibody suppresses NF-kappaB activation after IL-4 treatment, and IL
4-mediated induction of IL-17Rb is suppressed by IL-25 siRNA. IL-25 and IL-17Rb
promoter regions harbor putative NF-kappaB and STAT6 consensus sites, and
chromatin immunoprecipitation identified these transcription factors in complex
with the IL-17Rb 5' untranslated region. In bronchoalveolar lavage RNA
preparations, IL-25 and IL-17Rb mRNA transcripts are increased in asthmatics
compared with healthy control subjects, and IL-25 transcript abundance correlates
strongly with IL-4 mRNA levels. Thus, these results indicate that IL-4 signaling
up-regulates the IL-25 axis in human monocytic cells, and that IL-25 may provide
autocrine signals in monocytes and macrophages to sustain IL-17Rb expression and
predispose to alternative activation.
PMID- 28421821
TI - Modeling and dynamic simulation of astronaut's upper limb motions considering
counter torques generated by the space suit.
AB - Extravehicular activity (EVA) is an inevitable task for astronauts to maintain
proper functions of both the spacecraft and the space station. Both experimental
research in a microgravity simulator (e.g. neutral buoyancy tank, zero-g aircraft
or a drop tower/tube) and mathematical modeling were used to study EVA to provide
guidance for the training on Earth and task design in space. Modeling has become
more and more promising because of its efficiency. Based on the task analysis,
almost 90% of EVA activity is accomplished through upper limb motions. Therefore,
focusing on upper limb models of the body and space suit is valuable to this
effort. In previous modeling studies, some multi-rigid-body systems were
developed to simplify the human musculoskeletal system, and the space suit was
mostly considered as a part of the astronaut body. With the aim to improve the
reality of the models, we developed an astronauts' upper limb model, including a
torque model and a muscle-force model, with the counter torques from the space
suit being considered as a boundary condition. Inverse kinematics and the Maggi
Kane's method was applied to calculate the joint angles, joint torques and muscle
force given that the terminal trajectory of upper limb motion was known. Also, we
validated the muscle-force model using electromyogram (EMG) data collected in a
validation experiment. Muscle force calculated from our model presented a similar
trend with the EMG data, supporting the effectiveness and feasibility of the
muscle-force model we established, and also, partially validating the joint model
in kinematics aspect.
PMID- 28421822
TI - Deflation of a Rathke cleft cyst triggered rupture of a superior hypophyseal
artery aneurysm: a case report.
AB - A 57-year-old woman was diagnosed as a Rathke cleft cyst (RCC). Endoscopic
transsphenoidal surgery (TSS) was performed uneventfully. She developed
subarachnoid haemorrhage on postoperative day 3. The vessels adhered the cyst had
been pulled into the pituitary fossa, causing an aneurysm.
PMID- 28421823
TI - Tapia syndrome: an unusual complication following posterior cervical spine
surgery.
AB - Tapia syndrome, a rare complication of posterior cervical surgery, characterised
by concurrent paralyses of recurrent laryngeal branch of vagus and hypoglossal
cranial nerves, occurred in a patient after posterior cervical foraminotomies for
radiculopathy. We discuss hypothesised pathophysiology, and diagnostic,
therapeutic and avoidance strategies in relevance to prone neurosurgical
procedures.
PMID- 28421824
TI - Thrombosis of the draining vein causes intracranial haemorrhage in the natural
history of brain arteriovenous malformation: case report.
AB - Rupture of arteriovenous malformations (AVM) may be caused by venous outflow
restriction, but there is no radiographic evidence of this. We report a case
showing only a venous thrombus preceding intracranial haemorrhage from AVM. This
is the first evidence that venous thrombus results in AVM rupture in its natural
history.
PMID- 28421825
TI - Seizures in patients with acute pesticide intoxication, with a focus on
glufosinate ammonium.
AB - The incidence and clinical aspects of seizures remain to be elucidated in
patients with acute pesticide intoxication. The present study included subjects
who ingested pesticide with the intention of committing suicide and were treated
at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and
December 2014. We analyzed the incidence and characterized the type and frequency
of seizure, from the medical records of 464 patients with acute pesticide
intoxication, according to the pesticide class. The effect of seizure on the
clinical outcome was assessed. The incidence of seizure was 31.5% in patients who
ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl]
butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those
who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures
developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after
seizure initiation, following treatment with antiseizure medication. Generalized
tonic-clonic seizures were the most commonly observed (85.7% of the cases).
Multivariable logistic regression analysis showed that the effect of seizure on
mortality was not statistically significant. In conclusion, glufosinate ammonium
herbicide is the most common seizurogenic pesticide class. Seizure itself was not
a risk factor for mortality in patients with acute glufosinate ammonium
intoxication.
PMID- 28421826
TI - 6-Gingerol improves testicular function in mice model of chronic ulcerative
colitis.
AB - The persistent inflammation and oxidative stress at the local site in ulcerative
colitis reportedly extend to the testes via systemic circulation resulting in
testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound
isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in
mice was investigated in this study. Chronic ulcerative colitis was induced in
mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles.
Each cycle consisted of 7 consecutive days of exposure to DSS-treated water
followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or
sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination
with DSS-treated water during the three cycles. SZ served as standard reference
drug for colitis in this study. 6G significantly prevented the incidence of
rectal bleeding, decrease in the body weight gain and colon mass index in DSS
exposed mice. 6G significantly prevented colitis-mediated decreases in
luteinizing hormone, follicle-stimulating hormone and testosterone and decreases
oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with
concomitant augmentation of antioxidant enzymes activities, sperm
characteristics, marker enzymes of testicular function and histoarchitecture in
DSS-exposed mice. 6G exerted protective influence against ulcerative colitis
induced testicular damage via mechanisms involving its antioxidant and anti
inflammatory properties.
PMID- 28421827
TI - Pediatric Nandina domestica ingestions reported to poison centers.
AB - Nandina domestica is grown as an ornamental plant in the United States but has
also been reported as an invasive plant in a number of states. Parts of the
plant, particularly the berries, contain cyanogenic glycosides that convert to
hydrogen cyanide when ingested. This investigation characterized N. domestica
ingestions involving patients of age 5 years and less reported to Texas poison
centers during 2000-2015. There were 875 total N. domestica ingestions. A
seasonal pattern was observed with the highest proportion of ingestions occurring
in March (18.5%) and April (14.7%). The patients were male in 55.0% of the cases;
40.8% of the patients were of age 1 and 37.0% of age 2. Berries were specifically
mentioned in 709 ingestions, of which 57.3% involved one berry and 28.5% an
unknown number of berries. The ingestion occurred at the patient's own residence
in 92.9% of the cases, and the patient was managed on site in 97.0%. The most
frequently reported clinical effects were vomiting (3.7%), abdominal pain (1.0%),
diarrhea (0.9%), and nausea (0.7%). In conclusion, N. domestica ingestions among
young children generally do not result in serious outcomes and can be managed
successfully outside of a healthcare facility.
PMID- 28421828
TI - Jasmonic acid changes the composition of essential oil isolated from narrow
leaved lavender propagated in in vitro cultures.
AB - The aim of the present study was to determine the effect of jasmonic acid added
to the culture medium on composition of Lavandula angustifolia essential oils.
The chemical composition was determined by gas chromatography coupled to mass
detector (GC/MS). The experiment was conducted with the use of MS medium
supplemented with increasing concentration of JA (0.2, 0.5, 1, 1.5 mg?dm-3). It
was found that the analysed essential oils varied in terms of chemical
composition depending on the content of JA in the medium. All obtained essential
oils were characterised by a high content of sigma-cadinene (17.06-29.64%),
borneol (6.66-17.47%), caryophyllene oxide (8.30-14.01%), tau-cadinol (4.87
9.16%), beta-caryophyllene (3.54-6.57%), 1.8-cineole (1.94-5.87%), beta-pinene
(1.48-3.05%), geranyl acetate (0.56-2.14%) and myrtenal (0.65-2.14%).
PMID- 28421829
TI - Hydrocephalus and trigeminal neuralgia: exploring the association and management
options.
AB - We report the successful surgical management of three patients with trigeminal
neuralgia and hydrocephalus. MRI revealed no neurovascular contact at the
trigeminal root entry zone. Trigeminal neuralgic symptoms were controlled
following alleviation of hydrocephalus. We hypothesize that trigeminal nerve
traction, secondary to hydrocephalus, as the cause for their trigeminal
neuralgia.
PMID- 28421831
TI - A Novel Automated Slide-Based Technology for Visualization, Counting, and
Characterization of the Formed Elements of Blood: A Proof of Concept Study.
AB - CONTEXT: - A novel automated slide-based approach to the complete blood count and
white blood cell differential count is introduced. OBJECTIVE: - To present proof
of concept for an image-based approach to complete blood count, based on a new
slide preparation technique. A preliminary data comparison with the current flow
based technology is shown. DESIGN: - A prototype instrument uses a proprietary
method and technology to deposit a precise volume of undiluted peripheral whole
blood in a monolayer onto a glass microscope slide so that every cell can be
distinguished, counted, and imaged. The slide is stained, and then multispectral
image analysis is used to measure the complete blood count parameters. Images
from a 600-cell white blood cell differential count, as well as 5000 red blood
cells and a variable number of platelets, that are present in 600 high-power
fields are made available for a technologist to view on a computer screen. An
initial comparison of the basic complete blood count parameters was performed,
comparing 1857 specimens on both the new instrument and a flow-based hematology
analyzer. RESULTS: - Excellent correlations were obtained between the prototype
instrument and a flow-based system. The primary parameters of white blood cell,
red blood cell, and platelet counts resulted in correlation coefficients (r) of
0.99, 0.99, and 0.98, respectively. Other indices included hemoglobin (r = 0.99),
hematocrit (r = 0.99), mean cellular volume (r = 0.90), mean corpuscular
hemoglobin (r = 0.97), and mean platelet volume (r = 0.87). For the automated
white blood cell differential counts, r values were calculated for neutrophils (r
= 0.98), lymphocytes (r = 0.97), monocytes (r = 0.76), eosinophils (r = 0.96),
and basophils (r = 0.63). CONCLUSIONS: - Quantitative results for components of
the complete blood count and automated white blood cell differential count can be
developed by image analysis of a monolayer preparation of a known volume of
peripheral blood.
PMID- 28421830
TI - Sinonasal Inverted Papilloma: Risk Factors for Local Recurrence After Surgical
Resection.
AB - OBJECTIVES: Sinonasal inverted papillomas (SIP) present a potential for
recurrence years after the surgery, but most studies report short-term follow-up,
and risk factors for recurrence are still debated. Furthermore, several
classifications are described, and no consensus exists regarding which one should
be used. The aims of this study were to report our long-term results, investigate
for potential risk factors for recurrence, and compare the existing 8 staging
systems. METHODS: Over a 28-year period, 110 patients with a diagnosis of SIP
were enrolled. The median follow-up time was 55.6 months. RESULTS: In
multivariate Cox regression modeling, history of previous surgery was the only
variable associated with recurrence (hazard ratio = 4.91, 95% CI, 1.80-13.39).
Recurrences occurred up to 60 months after the surgery. Among the 8 staging
systems, none proved to be associated with recurrence. CONCLUSION: The only
factor associated with recurrence of SIP was prior surgery, probably
corresponding to an incomplete initial resection. Due to late recurrences, an
extended follow-up of at least 5 years is mandatory. In the absence of a
classification predicting prognosis, Krouse's staging system should be used to
homogenize studies' report since it is the most widely used.
PMID- 28421832
TI - Experimental induction of chicken amyloid A amyloidosis in white layer chickens
by inoculation with inactivated vaccines.
AB - We investigated the amyloidogenic potential of inactivated vaccines and the
localized production of serum amyloid A (SAA) at the injection site in white
layer chickens. Hens in the treated group were injected intramuscularly three
times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine
and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week
intervals. Chickens in the control group did not receive any inoculum. In the
treated group, emaciation and granulomas were present, while several chickens
died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at
necropsy, and the liver parenchyma showed inconsistent discolouration with patchy
green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage.
Amyloid deposition in the liver, spleen, duodenum, and at injection sites was
demonstrated using haematoxylin and eosin staining, Congo red, and
immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47%
(28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken
SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA
mRNA was detected by in situ hybridization in fibroblasts at the injection sites,
and also in hepatocytes. We believe that this is the first report of the
experimental induction of systemic AA amyloidosis in white layer chickens
following repeated inoculation with inactivated vaccines without the
administration of amyloid fibrils or other amyloid-enhancing factors.
PMID- 28421833
TI - A Multidimensional Study of Vocal Function Following Radiation Therapy for
Laryngeal Cancers.
AB - BACKGROUND: Radiation therapy (XRT) has proven to be an effective curative
modality in the treatment of laryngeal cancers. However, XRT also has deleterious
effects on vocal function. AIM: To demonstrate the multidimensional nature of
deficits in vocal function as a result of radiation therapy for laryngeal cancer.
STUDY DESIGN: Cohort study. METHODOLOGY: Vocal function parameters were chosen
from the 5 domains of voice assessment to complete a multidimensional assessment
battery. Adults irradiated (XRT group) for laryngeal cancers were compared to a
control group of individuals with no history of head and neck cancers or
radiation therapy. The control group was matched in age, sex, and pack years of
smoking. RESULTS: Eighteen participants were recruited for the study. The XRT
group demonstrated significantly worse clinical values as compared to the control
group across select parameters in the each of the 5 domains of voice assessment.
DISCUSSION: Radiation therapy for laryngeal cancers results in multidimensional
deficits in vocal function. Notably, these deficits persist long term. In the
present study sample, multidimensional deficits were persistent 2 to 7 years
following completion of XRT. The observed multidimensional persistent vocal
difficulties highlight the importance of vocal rehabilitation in the irradiated
larynx cancer population.
PMID- 28421835
TI - Symptomatic tension pneumocephalus following Palacos(r) cranioplasty in a shunted
patient.
AB - Tension pneumocephalus is an exceedingly rare complication of cerebrospinal fluid
diversion occurring after surgery, trauma or spontaneous fistula formation. We
report a case in a patient with a ventriculoperitoneal shunt who developed
symptomatic tension pneumocephalus via a skin defect within 24 hours of
undergoing bone cement cranioplasty.
PMID- 28421834
TI - Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk
of Cardiovascular Disease in Men with Hypogonadism: A Real-Life Observational
Registry Study Setting Comparing Treated and Untreated (Control) Groups.
AB - OBJECTIVES: In the absence of large, prospective, placebo-controlled studies of
longer duration, substantial evidence regarding the safety and risk of
testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can
only be gleaned from observational studies. To date, there are limited studies
comparing the effects of long-term TTh in men with hypogonadism who were treated
or remained untreated with T, for obvious reasons. We have established a registry
to assess the long-term effectiveness and safety of T in men in a urological
setting. Here, we sought to compare the effects of T on a host of parameters
considered to contribute to CV risk in treated and untreated men with
hypogonadism (control group). PATIENTS AND METHODS: Observational, prospective,
cumulative registry study in 656 men (age: 60.7 +/- 7.2 years) with total T
levels <=12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n
= 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an
initial 6-week interval for up to 10 years. Men (n = 296) who had opted against
TTh served as controls. Median follow-up in both groups was 7 years. Measurements
were taken at least twice a year, and 8-year data were analyzed. Mean changes
over time between the 2 groups were compared by means of a mixed-effects model
for repeated measures, with a random effect for intercept and fixed effects for
time, group, and their interaction. To account for baseline differences between
the 2 groups, changes were adjusted for age, weight, waist circumference, fasting
glucose, blood pressure, and lipids. RESULTS: There were 2 deaths in the T
treated group, none was related to CV events. There were 21 deaths in the
untreated (control) group, 19 of which were related to CV events. The incidence
of death in 10 patient-years was 0.1145 in the control group (95% confidence
interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95%
CI: 0.0023-0.0368; P < .000); the estimated difference between groups was 0.0804
(95% CI: 0.0189-0.3431; P < .001). The estimated reduction in mortality for the T
group was between 66% and 92%. There were also 30 nonfatal strokes and 26
nonfatal myocardial infarctions in the control group and none in the T-treated
group. CONCLUSION: Long-term TU was well tolerated with excellent adherence
suggesting a high level of patient satisfaction. Mortality related to CV disease
was significantly reduced in the T-group.
PMID- 28421836
TI - Analytical confirmation of synthetic cannabinoids in a cohort of 179
presentations with acute recreational drug toxicity to an Emergency Department in
London, UK in the first half of 2015.
AB - CONTEXT: Synthetic cannabinoid receptor agonists are the largest group of new
psychoactive substances reported in the last decade; in this study we
investigated how commonly these drugs are found in patients presenting to the
Emergency Department with acute recreational drug toxicity. METHODS: We conducted
an observational cohort study enrolling consecutive adult patients presenting to
an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with
acute recreational drug toxicity. Residual serum obtained from a serum sample
taken as part of routine clinical care was analyzed using high-resolution
accurate mass-spectrometry with liquid-chromatography (HRAM-LCMSMS). Minimum
clinical data were obtained from ED medical records. RESULTS: 18 (10%) of the 179
patient samples were positive for synthetic cannabinoid receptor agonists. The
most common was 5F AKB-48 (13 samples, concentration 50-7600 pg/ml), followed by
5F PB-22 (7, 30-400 pg/mL), MDMB-CHMICA (7, 80-8000 pg/mL), AB-CHMINACA (3, 50
1800 pg/mL), Cumyl 5F-PINACA (1, 800 pg/mL) and BB-22 (1, 60 pg/mL). Only 9/18
(50%) in whom synthetic cannabinoid receptor agonists were detected self-reported
synthetic cannabinoid receptor agonist use. The most common clinical features
were seizures and agitation, both recorded in four (22%) individuals. Fourteen
patients (78%) were discharged from the ED, one of the four admitted to hospital
was admitted to critical care. CONCLUSIONS: Synthetic cannabinoid receptor
agonists were found in 10% of this cohort with acute recreational drug toxicity
but self-reported in only half of these. This suggests that presentations to the
ED with acute synthetic cannabinoid receptor agonist toxicity may be more common
than reported.
PMID- 28421837
TI - Pediatric ingestion of vilazodone compared to other selective serotonin reuptake
inhibitor medications.
AB - BACKGROUND: Unintentional ingestion of selective serotonin reuptake inhibitor
(SSRI) medications is common amongst children <6 years of age. Current evidence
based management guidelines are based on a low incidence of significant medical
outcomes in these children. OBJECTIVE: To describe and compare outcomes of
pediatric exposures to vilazodone with other SSRIs. METHODS: A retrospective
observational case series analysis of both single and polysubstance SSRI
exposures amongst children <6 years old reported to the National Poison Data
System (NPDS). RESULTS: 11,384 SSRI exposures in children <6 years of age
reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone
only accounted for 5.9% of all exposures, but resulted in the highest proportion
of health care facility admission compared to other SSRIs, both in single
substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107
(53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have
higher odds of experiencing a major or moderate outcome in single (134 of 531
(25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7
9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such
as seizure and coma, were more common among the vilazodone exposures.
CONCLUSIONS: Exposure to vilazodone in this age group results in an increased
rate of hospitalization as well as more severe clinical effects as compared to
other SSRIs. Current evidence-based SSRI exposure management guidelines may not
be appropriate for the management of vilazodone ingestion in this age group.
PMID- 28421838
TI - Self-reported cocaine use is not associated with elevations in high-sensitivity
troponin I.
AB - OBJECTIVE: High-sensitivity troponin (hsTn) assays detect 10 times lower
concentrations of cardiac troponin than conventional assays. We examined the
effects of self-reported cocaine use to determine whether those with acute
cocaine use being evaluated for ACS are more likely to have elevated hsTnI than
those nonusers being evaluated for ACS. METHODS: We conducted a sub-analysis of a
prospective cohort of ED patients evaluated for acute coronary syndrome. Recent
cocaine use was determined by structured patient interviews. High-sensitivity
troponin (Abbott) and conventional troponin I (Abbott, cTnI) were measured on
samples drawn at presentation. Urine toxicology screen for cocaine metabolite was
obtained at the discretion of treating clinicians. RESULTS: Of 1862 patients
enrolled, 444 reported prior cocaine use and 99 reported cocaine use within the
preceding month. Median hsTn in patients with last cocaine use within 24 h, 2-7
days, 1 week-1 month, >1 month, and no prior cocaine use were: 9 (IQR: 3-17)
ng/L, 6 (IQR: 3-24.3) ng/L, 6 (IQR: 3-89.5) ng/L, 3 (IQR: 3-18.5) ng/L and 3
(IQR: 3-17) ng/L, respectively. Urine toxicology assays (UTox) for cocaine were
performed in 640 (34.4%) patients. The median hsTn for those who were UTox+, UTox
- and those without a UTox were: 9 ng/L (IQR: 3-48.5), 9 ng/L (IQR: 3-40) and 3
ng/L (IQR: 3-12), respectively. There were no differences in the prevalence of
new troponin elevations (hsTn >99th percentile but cTnI <99th percentile) in
those with recent cocaine use compared to those without recent cocaine use.
CONCLUSIONS: In this first investigation of hsTn in patients with self-reported
recent cocaine use, we have determined that hsTn does not lead to an increase in
the prevalence of troponin elevation in cocaine users.
PMID- 28421839
TI - Extracorporeal cardiopulmonary resuscitation after brown recluse envenomation.
PMID- 28421840
TI - Limitations of the evidence supporting use of undetectable acetaminophen levels
obtained <4 hours post-ingestion to rule out toxicity.
PMID- 28421841
TI - Adolescent with prolonged toxidrome.
AB - A 13-year-old female was presented to the emergency department following an
intentional ingestion. The patient developed significant toxicity including
multiple, discreet tonic-clonic seizures. Despite appropriate resuscitation and
antidotal management, the patient's symptoms persisted for more than 36 hours
post-ingestion. An upright abdominal radiograph was performed revealing a
radiopacity suggesting a pharmacobezoar. An esophagogastroduodenoscopy was
performed with successful removal of a tennis ball-sized pharmacobezoar. The
patient's symptoms subsequently subsided and she recovered fully with no
neurologic deficits. Diphenhydramine has not been previously identified as a
medication likely to form a pharmacobezoar and has not been shown to be
radiopaque. Though bezoar formation is a rare clinical scenario, it is one that
toxicologists must consider in patients with clinical courses that persist far
beyond expected based on known toxicokinetic principles.
PMID- 28421842
TI - The management of ventricular dysrhythmia in aconite poisoning.
AB - INTRODUCTION: Aconite poisoning is relatively rare but is frequently complicated
by ventricular dysrhythmias, which may be fatal. Molecular basis of aconite
alkaloid ventricular arrhythmogenicity: Aconite exerts its toxic effects due to
the presence of an admixture of alkaloids present in all parts of the plant. The
major target of these aconite alkaloids is the fast voltage-gates sodium channel,
where they cause persistent activation. This blockade of the channel in the
activated state promotes automaticity within the ventricular myocardium and the
generation of ventricular arrhythmias. Aconitine-induced arrhythmias: Aconite
alkaloids are known to cause many different types of disturbance of heart rhythm.
However, this focused review specifically looks at ventricular rhythm
disturbances, namely ventricular ectopy, ventricular tachycardia, torsades des
pointes and ventricular fibrillation. OBJECTIVE: The objective of this review was
to identify the outcome of anti-dysrhythmic strategies from animal studies and
case reports in humans in order to guide the management of ventricular
dysrhythmias in aconite poisoning in humans. METHODS: A review of the literature
in English was conducted in PubMed and Google Scholar from 1966 to July 2016
using the search terms "aconite/aconitine"; "aconite/aconitine + poisoning" and
"aconite/aconitine + dysrhythmia". 168 human case-reports and case-series were
identified by these searches, of which 103 were rejected if exposure to aconite
did not result in ventricular dysrhythmias, if it was uncertain as to whether
aconite had been ingested, if other agents were co-ingested, if there was
insufficient information to determine the type of treatments administered or if
there was insufficient information to determine outcome. Thus, 65 case reports of
probable aconite poisoning that resulted in ventricular dysrhythmias were
identified. Toxicokinetic data in aconite poisoning: Data were only available in
three papers; the presence of ventricular rhythm disturbances directly correlated
with the concentration of aconite alkaloids in the plasma. MANAGEMENT: 54 of 65
cases developed ventricular tachycardia, six developed torsades des pointes, 15
patients developed ventricular fibrillation, 10 developed ventricular ectopics
and one developed a broad complex tachycardia not otherwise specified; each
dysrhythmia was regarded as separate and patients may have had more than one
dysrhythmia. 10 patients died, giving a mortality of 15%. In total, 147
treatments were administered to 65 patients. 46 of the interventions were
assessed by the authors as having been associated with successful restoration of
sinus rhythm. Flecainide administration was accompanied by dysrhythmia
termination in six of seven cases. Mexiletine was connected with correcting
dysrhythmias in 3 of 3 cases. Procainamide administration was associated with
return to sinus rhythm in 2 of 2 cases. Prolonged cardio-pulmonary resuscitation
was administered to 15 patients where it was associated with a return to sinus
rhythm in nine of these. Amiodarone was linked to success in correcting
dysrhythmias in 11 of 20 cases. Cardiopulmonary bypass use was associated with a
return to sinus rhythm in four out of six cases. Epinephrine was documented as
being employed on four occasions, and was associated with a restoration of sinus
rhythm on two of these. Magnesium sulphate administration was accompanied by
dysrhythmia termination in two of nine cases. Direct cardioversion was associated
with a return of sinus rhythm in 5 of 30 cases. However, it is not certain
whether the drug treatment influenced the course of the dysrhythmia. CONCLUSIONS:
Based on the evidence available from human case reports, flecainaide or
amiodarone appear to be more associated with a return to sinus rhythm than
lidocaine and/or cardioversion, although it is not established whether the
administration of treatment caused reversion to normal sinus rhythm. The
potential beneficial effects of amiodarone were not observed in animal studies.
This may be due to intra-species differences between ion channels or relate to
the wider cardiovascular toxicity of aconite that extends beyond arrhythmias.
Prolonged cardiopulmonary resuscitation and cardiopulmonary bypass should be
considered as an integral part of good clinical care as "time-buying" strategies
to allow the body to excrete the toxic alkaloids. There may also be a role for
mexiletine, procainamide and magnesium sulphate.
PMID- 28421843
TI - Reply to: Limitations of the evidence supporting use of undetectable
acetaminophen levels obtained <4 hours post-ingestion to rule out toxicity.
PMID- 28421844
TI - Accuracy of the paracetamol-aminotransferase multiplication product to predict
hepatotoxicity in modified-release paracetamol overdose.
AB - CONTEXT: The paracetamol-aminotransferase multiplication product (APAP * ALT) is
a risk predictor of hepatotoxicity that is somewhat independent of time and type
of ingestion. However, its accuracy following ingestion of modified-release
formulations is not known, as the product has been derived and validated after
immediate-release paracetamol overdoses. OBJECTIVE: The aim of this retrospective
cohort study was to evaluate the accuracy of the multiplication product to
predict hepatotoxicity in a cohort of patients with modified-release paracetamol
overdose. METHODS: We assessed all patients with modified-release paracetamol
overdose presenting to our hospital network from October 2009 to July 2016.
Ingestion of a modified-release formulation was identified by patient self-report
or retrieval of the original container. Hepatotoxicity was defined as peak
alanine aminotransferase >=1000 IU/L, and acute liver injury (ALI) as a doubling
of baseline ALT to more than 50 IU/L. RESULTS: Of 1989 paracetamol overdose
presentations, we identified 73 modified-release paracetamol exposures treated
with acetylcysteine. Five patients developed hepatotoxicity, including one who
received acetylcysteine within eight hours of an acute ingestion. No patient with
an initial multiplication product <10,000 mg/L * IU/L developed hepatotoxicity
(sensitivity 100% [95%CI 48%, 100%], specificity 97% [90%, 100%]). Specificity
fell to 54% (95%CI: 34, 59%) at a product cut-off point <1500 mg/L * IU/L. When
calculated within eight hours of ingestion, mild elevations of the multiplication
product fell quickly on repeat testing in patients without ALI or hepatotoxicity.
CONCLUSIONS: In modified-release paracetamol overdose treated with
acetylcysteine, the paracetamol-aminotransferase multiplication product
demonstrated similar accuracy and temporal profile to previous reports involving
mostly immediate-release formulations. Above a cut-point of 10,000 mg/L * IU/L,
it was very strongly associated with the development of acute liver injury and
hepatotoxicity, especially when calculated more than eight hours post-ingestion.
When below 1500 mg/L * IU/L the likelihood of developing hepatotoxicity was very
low. Persistently high serial multiplication product calculations were associated
with the greatest risk of hepatotoxicity.
PMID- 28421845
TI - An alarming increase in local pentobarbital-related suicides.
PMID- 28421846
TI - Clinical toxicology: past and future.
PMID- 28421847
TI - Authors' Response to Letter to the Editor, Part II.
PMID- 28421848
TI - An Evaluation of a Community-Oriented Policing Program in Taiwan.
AB - This study was conducted to evaluate the effect of a community-oriented policing
(COP) by documenting results for 16 quantitative outcome variables, including
crime incidents, crime clearance, residents' subjective feelings regarding police
performance and community safety, and job satisfaction among police officers. The
statistical techniques used to analyze the data involved ARIMA interrupted time
series, t tests, the Wilcoxon paired signed-rank test, and Pearson's correlation.
The quantitative results observed indicated that the program had a positive
effect on resident's perceptions for some police performance outcomes and for job
satisfaction among police officers. However, there was only a minimal program
effect on crime occurrence, crime clearance, and residents' perceptions of crime.
Using a combination of review of prior research and qualitative interview data
collected from 10 local stakeholders, we provided insightful informed actor-based
and temporal contextual explanations for the unexpected quantitative findings.
PMID- 28421849
TI - Infliximab crystal structures reveal insights into self-association.
AB - Aggregation and self-association in protein-based biotherapeutics are critical
quality attributes that are tightly controlled by the manufacturing process.
Aggregates have the potential to elicit immune reactions, including neutralizing
anti-drug antibodies, which can diminish the drug's efficacy upon subsequent
dosing. The structural basis of reversible self-association, a form of non
covalent aggregation in the native state, is only beginning to emerge for many
biologics and is often unique to a given molecule. In the present study, crystal
structures of the infliximab (Remicade) Fc and Fab domains were determined. The
Fab domain structures are the first to be reported in the absence of the antigen
(i.e., tumor necrosis factor), and are consistent with a mostly rigid
complementarity-determining region loop structure and rotational flexibility
between variable and constant regions. A potential self-association interface is
conserved in two distinct crystal forms of the Fab domain, and solution studies
further demonstrate that reversible self-association of infliximab is mediated by
the Fab domain. The crystal structures and corresponding solution studies help
rationalize the propensity for infliximab to self-associate and provide insights
for the design of improved control strategies in biotherapeutics development.
PMID- 28421850
TI - Semen parameters and pregnancy rates after microsurgical varicocelectomy in
primary versus secondary infertile men.
AB - In a prospective study, the outcomes of microsurgical varicocelectomy in men with
primary versus secondary infertility were compared. Ninety-two infertile men with
a varicocele were included. They were classified into those with primary
infertility (n = 57) and secondary infertility (n = 35). Clinical data, semen
parameters and scrotal ultrasound finding were available for all patients and
microsurgical varicocelectomy was performed on all of them. Spontaneous pregnancy
rates and improvement in semen parameters in those men with primary versus
secondary infertility were recorded 1 year after surgery. Preoperatively, there
was no significant difference in the mean semen parameters in both groups (p >
0.05) and the mean semen parameters showed no significant difference between men
with primary and secondary infertility. After microsurgical varicocelectomy, the
mean semen parameters improved significantly in both group (p < 0.05 for each),
but there were no significant difference in mean semen parameters between men
with primary versus secondary infertility (p > 0.05 for each). After adjustment
for patient and partner ages, the pregnancy rate at the end of the follow-up
period did not significantly differ between the primary (24/57, 42.1%) and
secondary (11/35, 31.4%) infertility group (Pearson's Chi-squared = 1.05). We
concluded from this study that semen parameters and pregnancy rates after
microsurgical varicocelectomy were similar between men with primary and secondary
infertility.
PMID- 28421851
TI - Global and multi-focal changes in cerebral blood flow during subthalamic nucleus
stimulation in Parkinson's disease.
AB - Electrical stimulation of subthalamic nuclei (STN) is a widely used therapy in
Parkinson's disease (PD). While deep brain stimulation (DBS) of the STN alters
the neurophysiological activity in basal ganglia, the therapeutic mechanism has
not been established. A positron emission tomography (PET) study of cerebral
blood flow (CBF) during speech production in PD subjects treated with STN-DBS
found significant increases in global (whole-brain) CBF.1 That study utilized a
series of whole-slice regions of interest to obtain global CBF values. The
present study examined this effect using a voxel-based principal component
analysis (PCA) combined with Fisher's linear discriminant analysis (FLDA) to
classify STN-DBS on versus STN-DBS off whole-brain images. The approach yielded
wide-spread CBF changes that classified STN-DBS status with accuracy,
sensitivity, and specificity approaching 90%. The PCA component of the analysis
supported the observation of a global CBF change during STN-DBS. The FLDA
component demonstrated wide-spread multi-focal CBF changes. Further, CBF
measurements related to a number of subject characteristics when STN-DBS was off,
but not when it was on, suggesting that the normal relationship between CBF and
behavior may be disrupted by this form of neuromodulation.
PMID- 28421852
TI - The Priorities of Iranian Male Adolescents Health Needs.
AB - Health in the adolescence period guarantees the next generation's health. The
assessment of health needs is the first stage for the implementation of health
promotion interventions. This study aimed to assess the priorities of male
adolescent's health needs in Tehran, Iran, in year 2015. This cross-sectional
correlational study was conducted with 1,200 male adolescents aged between 13 and
18 years. Single male adolescents studying in public guidance and high schools in
Tehran, Iran, in year 2015 were chosen using a random multistage sampling method.
Data were collected using the male adolescent health need assessment scale. The
data were analyzed using descriptive and inferential statistics. It was found
that while the lowest score was for the domain of sexual health, other domains
had average or higher than average scores. More attention should be paid to the
sexual health needs of male adolescents. Policy makers need to design strategies
that help meet the health needs of male adolescents.
PMID- 28421853
TI - Pentraxin 3 and lipid profile status in pregnancy.
AB - Hyperlipidaemia and hypercholesterolaemia are risk factors of atherosclerosis and
cardiovascular disease. The reference range of lipids during pregnancy has not
yet been clearly set. This study sought to measure lipid parameters and pentraxin
(PTX) 3 levels in low-risk pregnant women. The participants had serial blood
samples taken between their 6th-9th week, 10th-13th week, 14th-19th week, 24th
29th week and 35th-40th week (as long as there were no contractions), during the
labour period, and 2 days after delivery. The same tests were carried out on cord
blood after delivery. There were 116 participants, of which 72 were included in
the study and 44 were excluded. Total-c, HDL-c, LDL-c, TG and PTX3 increased as
the pregnancy progressed. During labour, Total-c, HDL-c, LDL-c and PTX3
increased, but TG decreased. After delivery, TG and PTX3 increased but other
parameters decreased from the value measured during the 35th-40th week. This
study measured changes in lipid profiles and PTX3 during pregnancy, labour and
after delivery, establishing a foundation for future studies.
PMID- 28421854
TI - Reduction of BOLD interference in pseudo-continuous arterial spin labeling:
towards quantitative fMRI.
AB - Fluctuations in blood-oxygenation level dependent (BOLD) signal and perfusion
affect the quantification of changes in cerebral blood flow (CBF), coupled to
neuronal activity, in arterial spin labeling (ASL). Subtraction methods for
control and labeled MR images (i.e. pair-wise, surround subtraction, and
subtraction of sinc-interpolated images), postulated to mitigate this
interference in pseudo-continuous ASL (pCASL), were evaluated by comparison with
quantitative 15O-water PET. At rest, a good agreement in the CBF values was found
between PET and MRI for each of the subtraction methods. Stimulation of the
visual system resulted in a regional CBF increase in the occipital lobe, which
was detectable in both modalities. Bland-Altman analysis showed a systematic
underestimation of the CBF values during activation in MRI. Evaluation of the
relative CBF change induced by neuronal stimulation showed good inter-modality
agreement for the three subtraction methods. Perfusion data obtained with each
subtraction method followed the stimulation paradigm without significant
differences in the correlation patterns or in the time lag between stimulation
and perfusion response. Comparison to the gold standard confirmed the
detectability of a neuronal stimulation pattern by pCASL. The results indicate
that the combined use of background suppression and short TE reduces the BOLD
weighting in the pCASL signal.
PMID- 28421855
TI - Midterm Outcomes After Infrapopliteal Interventions in Patients With Critical
Limb Ischemia Based on the TASC II Classification of Below-the-Knee Arteries.
AB - PURPOSE: To analyze the relationship between the new TransAtlantic Inter-Society
Consensus (TASC II) infrapopliteal classification and limb outcomes among
patients with critical limb ischemia (CLI). METHODS: A single-center
retrospective study was performed on 166 consecutive CLI patients (mean age 71
years; 113 men) undergoing endovascular treatment of 244 infrapopliteal lesions
from 2006 to 2013. Patient, procedural, angiographic, and limb outcomes were
compared for the new TASC A/B vs C/D classification for infrapopliteal lesions.
Binary restenosis was determined by a peak systolic velocity ratio >2.0 by duplex
ultrasound on follow-up at 1, 3, 6, and 12 months. RESULTS: Seventy-two (43.4%)
patients had TASC A/B lesions, while 94 (56.6%) had TASC C/D patterns of
infrapopliteal disease. Baseline demographics and tissue loss (93% vs 94%,
p=0.59) were similar between the groups. TASC A/B lesions were shorter (53+/-35
vs 170+/-83 mm, p<0.001), less severely stenosed (77%+/-24% vs 93%+/-14%,
p<0.001), had a larger target vessel diameter (2.9+/-0.5 vs 2.6+/-0.5 mm,
p<0.001), and were less frequently chronic total occlusions (24% vs 64%, p<0.001)
compared with the TASC C/D group. Three-year freedom from both amputation (85% vs
67%, p=0.02) and major adverse limb events (79% vs 61%, p=0.02) were
significantly higher in the TASC A/B group. Technical success rates (95% vs 80%,
p<0.001) and 1-year primary patency (58% vs 51%, p=0.04) were higher in the A/B
group. Overall 3-year survival was similar between the groups (96% A/B vs 88%
C/D, p=0.2). CONCLUSION: TASC C/D infrapopliteal lesions are associated with
higher amputation and major adverse limb events rates and lower primary patency
compared with TASC A/B infrapopliteal lesions. Further studies are needed to
assess the association between TASC C/D infrapopliteal lesions and clinical
outcomes in patients with CLI.
PMID- 28421856
TI - Evaluation of the simplified acute physiology score (SAPS-OB) in critically ill
obstetric patients.
PMID- 28421857
TI - Risk of solid cancer in low dose-rate radiation epidemiological studies and the
dose-rate effectiveness factor.
AB - PURPOSE: Estimated radiation risks used for radiation protection purposes have
been based primarily on the Life Span Study (LSS) of atomic bomb survivors who
received brief exposures at high dose rates, many with high doses. Information is
needed regarding radiation risks from low dose-rate (LDR) exposures to low linear
energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR
epidemiologic studies that provide dose-response estimates of total solid cancer
risk in adulthood in comparison to corresponding LSS risks, in order to estimate
a dose rate effectiveness factor (DREF). MATERIALS AND METHODS: We identified 22
LDR studies with dose-response risk estimates for solid cancer after minimizing
information overlap. For each study, a parallel risk estimate was derived from
the LSS risk model using matching values for sex, mean ages at first exposure and
attained age, targeted cancer types, and accounting for type of dosimetric
assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR
Gy-1) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta
analysis of the risk ratios was conducted. The reciprocal of the resultant risk
ratio provided an estimate of the DREF. RESULTS: The meta-analysis showed a
LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19
studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts
with only incidence data also were added, implying a DREF with values around 3,
but statistically compatible with 2. However, the analyses were highly dominated
by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk
ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09,
0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta
analyses that included only cohorts in which the mean dose was <100 mGy yielded a
risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95%
CI 0.10, 1.06) for mortality + incidence data. CONCLUSIONS: The interpretation of
a best estimate for a value of the DREF depends on the appropriateness of
including the Mayak study. This study indicates a range of uncertainty in the
value of DREF between 1 and about 2 after protracted radiation exposure. The LDR
data provide direct evidence regarding risk from exposures at low dose rates as
an important complement to the LSS risk estimates used for radiation protection
purposes.
PMID- 28421858
TI - Multi-step treatment for acquired alexia and agraphia (Part I): efficacy,
generalisation, and identification of beneficial treatment steps.
AB - Reading and writing impairments are common in individuals with post-stroke
aphasia. Treatment typically aims to improve the function of one of these
modalities by strengthening aspects of either lexical or sublexical processing.
In the present study, eight adults with acquired alexia and agraphia were
administered a comprehensive treatment targeting specific lexical and sublexical
processes underlying reading and/or writing. Two participants were trained in
reading and six were trained in writing. Throughout treatment, reading and
writing accuracy were monitored for trained items, as well as untrained but
orthographically and semantically related items. Linear mixed effects models
indicated that the most substantial gains were made on trained items in the
trained modality; generalisation to trained items in the untrained modality and
untrained but related items in both modalities was also observed. Participants
improved significantly on a subset of treatment steps intended to address lexical
access and representations, sublexical conversion mechanisms, and the graphemic
and/or phonological buffer processes in both modalities. These results
demonstrate the efficacy of a novel, comprehensive treatment protocol and suggest
that targeting multiple reading and writing processes in conjunction may
facilitate widespread generalisation.
PMID- 28421860
TI - Abstracts of Presentations at the 2017 Southern Division Meeting.
PMID- 28421859
TI - Water Sensation During Passive Propulsion for Expert and Nonexpert Swimmers.
AB - This study determined whether expert swimmers, compared with nonexperts, have
superior movement perception and physical sensations of propulsion in water.
Expert (national level competitors, n = 10) and nonexpert (able to swim 50 m in >
3 styles, n = 10) swimmers estimated distance traveled in water with their eyes
closed. Both groups indicated their subjective physical sensations in the water.
For each of two trials, two-dimensional coordinates were obtained from video
recordings using the two-dimensional direct linear transformation method for
calculating changes in speed. The mean absolute error of the difference between
the actual and estimated distance traveled in the water was significantly lower
for expert swimmers (0.90 +/- 0.71 meters) compared with nonexpert swimmers (3.85
+/- 0.84 m). Expert swimmers described the sensation of propulsion in water in
cutaneous terms as the "sense of flow" and sensation of "skin resistance."
Therefore, expert swimmers appear to have a superior sense of distance during
their movement in the water compared with that of nonexpert swimmers. In
addition, expert swimmers may have a better perception of movement in water. We
propose that expert swimmers integrate sensations and proprioceptive senses,
enabling them to better perceive and estimate distance moved through water.
PMID- 28421862
TI - Lateral Wall Regeneration and Membrane Repair After Attempted Sinus Augmentation
Using a Non-Resorbable Membrane.
PMID- 28421861
TI - The Plant-Dependent Life Cycle of Thecaphora thlaspeos: A Smut Fungus Adapted to
Brassicaceae.
AB - Smut fungi are globally distributed plant pathogens that infect agriculturally
important crop plants such as maize or potato. To date, molecular studies on
plant responses to smut fungi are challenging due to the genetic complexity of
their host plants. Therefore, we set out to investigate the known smut fungus of
Brassicaceae hosts, Thecaphora thlaspeos. T. thlaspeos infects different
Brassicaceae plant species throughout Europe, including the perennial model plant
Arabis alpina. In contrast to characterized smut fungi, mature and dry T.
thlaspeos teliospores germinated only in the presence of a plant signal. An
infectious filament emerges from the teliospore, which can proliferate as haploid
filamentous cultures. Haploid filaments from opposite mating types mate, similar
to sporidia of the model smut fungus Ustilago maydis. Consistently, the a and b
mating locus genes are conserved. Infectious filaments can penetrate roots and
aerial tissues of host plants, causing systemic colonization along the
vasculature. Notably, we could show that T. thlaspeos also infects Arabidopsis
thaliana. Exploiting the genetic resources of A. thaliana and Arabis alpina will
allow us to characterize plant responses to smut infection in a comparative
manner and, thereby, characterize factors for endophytic growth as well as smut
fungi virulence in dicot plants.
PMID- 28421863
TI - A meta-analysis of task-related influences in prospective memory in traumatic
brain injury.
AB - Prospective memory is the ability to remember to do something in the future and
it is essential to every-day functional independence. Traumatic brain injury is
associated with frequent and persistent prospective memory deficits. This study
presents a review and meta-analysis investigating the effects of task parameters
on prospective memory performance of individuals with TBI. Individual studies
using continuous behavioural measures of prospective memory with a sample of
adults with TBI and matched controls were included. Consistent with previous
research, a random effects meta-analysis indicated that TBI groups demonstrated
lower prospective memory performance than control groups (d = 1.10, SE = 0.12,
95% CI = 0.86-1.34). In addition, we found that type of prospective memory cue,
saliency of cues, and complexity of the ongoing task significantly moderated the
difference in prospective memory performance between TBI and control groups.
These findings suggest that prospective memory task parameters should be
considered in the assessment of prospective memory in individuals with cognitive
impairment. In addition, considering the influence of these task parameters would
be useful to develop effective compensatory strategies to reduce prospective
memory failures.
PMID- 28421864
TI - Selfie: Autoimmunity, boon or bane.
AB - The immune system provides protection to tissues damaged by infectious
microrganisms or physical damage. In autoimmune diseases, the immune system
recognizes and attacks its own tissues, i.e., self-destruction. Various agents
such as genetic factors and environmental triggers are thought to play a major
role in the development of autoimmune diseases. A common feature of all
autoimmune diseases is the presence of autoantibodies and inflammation, including
mononuclear phagocytes, autoreactive T lymphocytes, and autoantibody producing B
cells (plasma cells). It has long been known that B cells produce autoantibodies
and, thereby, contribute to the pathogenesis of many autoimmune diseases.
Autoimmune diseases can be classified as organ-specific or non-organ specific
depending on whether the autoimmune response is directed against a particular
tissue or against widespread antigens as in chronic inflammatory autoimmune
diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis
(RA). Both SLE and RA are characterized by the presence of autoantibodies which
play a major role in their etiopathogenesis. SLE is characterized by circulating
antibodies and immune complex deposition that can trigger an inflammatory damage
in organs. RA is a progressive inflammatory disease in which T cells, B cells,
and pro-inflammatory cytokines play a key role in its pathophysiology.
PMID- 28421865
TI - It's not all about moral reasoning: Understanding the content of Moral Case
Deliberation.
AB - BACKGROUND: Moral Case Deliberation is one form of clinical ethics support
described as a facilitator-led collective moral reasoning by healthcare
professionals on a concrete moral question connected to their practice.
Evaluation research is needed, but, as human interaction is difficult to
standardise, there is a need to capture the content beyond moral reasoning. This
allows for a better understanding of Moral Case Deliberation, which may
contribute to further development of valid outcome criteria and stimulate the
normative discussion of what Moral Case Deliberation should contain. OBJECTIVE:
To explore and compare the content beyond moral reasoning in the dialogue in
Moral Case Deliberation at Swedish workplaces. METHODS: A mixed-methods approach
was applied for analysing audio-recordings of 70 periodic Moral Case Deliberation
meetings at 10 Swedish workplaces. Moral Case Deliberation facilitators and
various healthcare professions participated, with registered nurses comprising
the majority. Ethical considerations: No objection to the study was made by an
Ethical Review Board. After oral and written information was provided, consent to
be recorded was assumed by virtue of participation. FINDINGS: Other than 'moral
reasoning' (median (md): 45% of the spoken time), the Moral Case Deliberations
consisted of 'reflections on the psychosocial work environment' to a varying
extent (md: 29%). Additional content comprised 'assumptions about the patient's
psychosocial situation' (md: 6%), 'facts about the patient's situation' (md: 5%),
'concrete problem-solving' (md: 6%) and 'process' (md: 3%). CONCLUSION: The
findings suggest that a restorative function of staff's wellbeing in Moral Case
Deliberation is needed, as this might contribute to good patient care. This
supports outcome criteria of improved emotional support, which may include relief
of moral distress. However, facilitators need a strategy for how to proceed from
the participants' own emotional needs and to develop the use of their emotional
knowing to focus on the ethically difficult patient situation.
PMID- 28421866
TI - Chronic Pain and Psychological Distress Among Older Adults: A National
Longitudinal Study.
AB - This research examines whether unobserved time-stable influences confound the
association between chronic pain and psychological distress in older adults as
well as how race and ethnicity combine with subjective social status (SSS) to
modify the association. In a nationally representative longitudinal survey,
holistically controlling for unobserved time-stable influences using fixed
effects models substantially reduces the pain-depression relationship and
eliminates the overall pain-anxiety relationship. The association with depression
is stronger for Black and Hispanic elders, illustrating a process of double
jeopardy. Black elders with severe pain experience lower anxiety, as do Black
elders with moderate pain and low SSS, which we suggest may be due to the
enervating effects of undermanaged pain. Black elders at high SSS experience
greater anxiety with moderate pain. This research suggests that undermanagement
of chronic pain among racial and ethnic minorities differentiates the association
between pain and distress in late life and especially creates stronger
associations with depression.
PMID- 28421867
TI - Symptom-related attributional biases in schizophrenia and bipolar disorder.
AB - INTRODUCTION: Biases in causal attributions and evidence integration have been
implicated in delusions, but have not been investigated simultaneously to examine
additive or multiplicative effects. It was hypothesised that paranoid delusions
would correlate with self-serving and personalising biases ("defence" model of
paranoia), particularly when these biases were disconfirmed. METHODS: Constrained
principal component analysis was used to investigate differences between
schizophrenia patients (paranoid vs. non-paranoid), bipolar disorder patients,
and healthy controls, as well as to examine the extent to which psychotic
symptoms could predict patterns of responding on a novel attributional bias task
(Attributional Style BADE, or ASB) that requires integrating contextual
information. RESULTS: Although no group differences were found, disorganisation
and manic symptoms correlated with situation attributions and self-blame when
such attributions were unsupported by the available evidence, and depression and
anxiety correlated with other-person and self attributions (not situation
attributions) when confirmed by the available evidence, regardless of diagnosis.
CONCLUSIONS: While group differences accounted for little variance in responses
on the ASB task, a transdiagnostic association between symptoms of psychosis and
the ASB task was observed. This highlights the importance of considering symptom
profiles rather than diagnostic groupings when investigating cognitive biases and
related non-pharmacological treatments.
PMID- 28421868
TI - RKNNMDA: Ranking-based KNN for MiRNA-Disease Association prediction.
AB - Cumulative verified experimental studies have demonstrated that microRNAs
(miRNAs) could be closely related with the development and progression of human
complex diseases. Based on the assumption that functional similar miRNAs may have
a strong correlation with phenotypically similar diseases and vice versa,
researchers developed various effective computational models which combine
heterogeneous biologic data sets including disease similarity network, miRNA
similarity network, and known disease-miRNA association network to identify
potential relationships between miRNAs and diseases in biomedical research.
Considering the limitations in previous computational study, we introduced a
novel computational method of Ranking-based KNN for miRNA-Disease Association
prediction (RKNNMDA) to predict potential related miRNAs for diseases, and our
method obtained an AUC of 0.8221 based on leave-one-out cross validation. In
addition, RKNNMDA was applied to 3 kinds of important human cancers for further
performance evaluation. The results showed that 96%, 80% and 94% of predicted top
50 potential related miRNAs for Colon Neoplasms, Esophageal Neoplasms, and
Prostate Neoplasms have been confirmed by experimental literatures, respectively.
Moreover, RKNNMDA could be used to predict potential miRNAs for diseases without
any known miRNAs, and it is anticipated that RKNNMDA would be of great use for
novel miRNA-disease association identification.
PMID- 28421869
TI - ALK protein expression in pulmonary adenocarcinoma of Tunisian patients.
AB - BACKGROUND: It is now necessary to determine ALK status in order to use targeted
therapy. AIM: herein, we assess immunohistochemical profile of ALK protein in a
series of Tunisian patients with pulmonary adenocarcinoma. MATERIALS AND METHODS:
ALK protein expression was studied applying the D5F3 antibody with a fully
automated Ventana CDx technique on a series of 19 patients. RESULTS: Positive ALK
expression was found in one case (5.2%) corresponding to a papillary
adenocarcinoma which showed a strong granular and homogenous cytoplasmic
staining. The patient was a 30-years-old woman. CONCLUSION: The frequency of
positive ALK expression based on immunohistochemistry in our series was similar
to that reported in the world literature.
PMID- 28421870
TI - Collaborative study on the effect of grinding on the detection of bones from
processed animal proteins in feed by light microscopy.
AB - Bone fragments are essential structures for the detection of processed animal
proteins (PAPs) in feed by light microscopy for official controls according to
Annex VI of European Union Regulation EC/152/2009. The preparation of samples
submitted for analysis requires a grinding step to make them suitable for
microscopic slide preparation and observation. However, there are no technical
guidelines set down for this step despite the fact that it can lead to an
increase in bone numbers due to fragmentation. This was demonstrated by an in
house study carried out by the Irish National Reference Laboratory (NRL) for
animal protein detection. The present collaborative study investigated the
possible effects of three different grinding conditions on the final result for a
feed adulterated with 0.05 and 0.01% (w/w) of PAP. The microscopic analysis
either combined or not with an Alizarin Red staining was carried out by 10
different laboratories. The results demonstrated that although a large variation
in the numbers of bone fragments was noted, five of the six different
grinding/staining combinations applied at two levels of PAP adulteration did not
significantly (at p = 0.05) differ from one another. The only exception occurred
when grinding the feed containing 0.05% of PAP with a rotor mill equipped with a
0.5-mm sieve and combined with a staining which resulted in a greater number of
bone fragments by forced fragmentation. Overall, the impact of the
grinding/staining combinations on the final results was shown to be negligible
when considering the regulatory limit of detection (LOD) requirement for the
method and the current rules of implementation of the light microscopic method.
From a total of 180 analyses carried out on the feed matrix containing 0.05% of
PAP no false-negative result was observed, and at a level of 0.01% PAP only 10
false-negative results occurred.
PMID- 28421871
TI - Exploring predictors of work competence in schizophrenia: The role of theory of
mind.
AB - In schizophrenia employment rate is dramatically low, also among patients
receiving job support interventions. Recent studies showed a direct relationship
between neurocognitive deficits and work functioning, as well as proving the
benefits of combined neurocognitive and work interventions. Current evidence also
supports a role of Theory of Mind (ToM), on work functioning. However, the effect
of integrated rehabilitation programmes including a social cognitive training on
job outcome is still less explored. The aim of this pilot study is to investigate
the relationship between work competence and clinical factors, neurocognitive and
ToM abilities, as well as to explore the effect of neurocognitive and ToM
treatments combined with work therapy. Thirty-seven outpatients with
schizophrenia were assigned to either a Computer-assisted Cognitive Remediation
(CACR) plus work therapy group (WTG) or to CACR and WTG added to ToM
Intervention, both followed by a job support programme. All patients were
assessed for psychopathology, neurocognition, ToM and work functioning. Work
outcome was significantly predicted by age at onset, neurocognitive abilities and
the degree of ToM improvement after the specific intervention. This study
provides preliminary insight on predictors of work competence in schizophrenia,
highlighting the importance of ToM abilities.
PMID- 28421872
TI - Role of valued living and associations with functional outcome following
traumatic brain injury.
AB - Valued living (VL) is associated with improved enjoyment and engagement with
daily activities despite negative emotional state or ongoing pain. However, the
role of VL in recovery following traumatic brain injury (TBI) has yet to be
investigated. This study aimed to examine changes in VL over the course of
recovery and variables associated with VL. Participants with moderate-to-severe
TBI were recruited from a rehabilitation hospital in three cohorts: "Early" (n =
25), "Mid" (n = 9) and "Late" (n = 36) post-TBI. All participants were assessed
at time of recruitment and 12 months later. The main measure was the Valued
Living Questionnaire. Compared to pre-injury estimates, VL was significantly
reduced at 12 months post-injury. Levels of VL remained reduced between 2 and 3
years and increased between 3 and 6 years post-injury. VL was strongly associated
with improved functional and psychosocial outcomes. Changes in VL occur over at
least 3-5 years post-injury, with 12 months post-TBI a suitable time for
intervention given VL remains low over the next 24 to 36 months post injury.
Targeted intervention to modify values and/or valued activities to be consistent
with post-injury capacity could improve rates of return to pre-injury levels of
VL.
PMID- 28421873
TI - Facial Alveolar Bone Width at the First and Second Maxillary Premolars in Healthy
Patients: A Cone Beam Computed Tomography Study.
AB - The purpose of this study was to analyze the thickness of the facial alveolar
bone at the first and second maxillary premolars and determinate the percentage
of premolars that reached 2 mm in width. A retrospective study was performed,
analyzing cone beam computed tomography scans from the database of the Oral
Surgery Unit of the University of Valencia. Patients with periodontal disease,
orthodontic treatment, absence among the first maxillary molars, premolars with
endodontic treatment, or prosthetic restorations were excluded. The facial
alveolar bone width was measured at 1, 2, 3, and 5 mm apical to the vestibular
bone peak. A total of 44 patients were included in the study, with 72 first
premolars and 72 second premolars analyzed. A descriptive analysis was performed
and the normal means were assessed using the Kolmogorov-Smirnov test. The average
width of the facial alveolar bone at first and second maxillary premolars was
respectively: 1.41 +/- 0.50 and 1.72 +/- 0.56 at 1 mm, 1.68 +/- 0.72 and 2.23 +/-
0.66 at 2 mm, 1.71 +/- 0.89 and 2.43 +/- 0.82 at 3 mm, 1.44 +/- 1.00 and 2.31 +/-
1.06 at 5 mm from the vestibular bone peak. The facial alveolar bone width at the
second maxillary premolars was greater than at the first maxillary premolars at
all points measured. This information should be taken in account when planning
immediate implants. Further studies are needed to analyze bone resorption at
maxillary premolars to better understand facial alveolar bone width influence in
implant treatment.
PMID- 28421874
TI - Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate
mixture/oxycodone transdermal patch system: a Phase I study.
AB - AIM: To characterize the pharmacokinetic profile and evaluate the safety and
tolerability of a transdermal oxycodone patch containing tocopheryl phosphate
mixture (TPM). PATIENTS & METHODS: Eleven healthy subjects received a single
application of three TPM/oxycodone patches applied to the torso for 72 h.
RESULTS: Oxycodone was detected 8.0 +/- 2.7-h postpatch administration, reaching
a mean maximum plasma concentration of 3.41 +/- 1.34 ng/ml at 49.3 +/- 21.2 h.
The safety profile was consistent with the application method and known side
effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation
was observed. CONCLUSION: A 3-day application of the TPM/oxycodone patch
demonstrated an acceptable safety profile and was well tolerated by healthy
subjects, with limited dermal irritation following application.
PMID- 28421875
TI - Three-Dimensional Printing and Its Applications in Otorhinolaryngology-Head and
Neck Surgery.
AB - Objective Three-dimensional (3D)-printing technology is being employed in a
variety of medical and surgical specialties to improve patient care and advance
resident physician training. As the costs of implementing 3D printing have
declined, the use of this technology has expanded, especially within surgical
specialties. This article explores the types of 3D printing available, highlights
the benefits and drawbacks of each methodology, provides examples of how 3D
printing has been applied within the field of otolaryngology-head and neck
surgery, discusses future innovations, and explores the financial impact of these
advances. Data Sources Articles were identified from PubMed and Ovid MEDLINE.
Review Methods PubMed and Ovid Medline were queried for English articles
published between 2011 and 2016, including a few articles prior to this time as
relevant examples. Search terms included 3-dimensional printing, 3 D printing,
otolaryngology, additive manufacturing, craniofacial, reconstruction, temporal
bone, airway, sinus, cost, and anatomic models. Conclusions Three-dimensional
printing has been used in recent years in otolaryngology for preoperative
planning, education, prostheses, grafting, and reconstruction. Emerging
technologies include the printing of tissue scaffolds for the auricle and nose,
more realistic training models, and personalized implantable medical devices.
Implications for Practice After the up-front costs of 3D printing are accounted
for, its utilization in surgical models, patient-specific implants, and custom
instruments can reduce operating room time and thus decrease costs. Educational
and training models provide an opportunity to better visualize anomalies,
practice surgical technique, predict problems that might arise, and improve
quality by reducing mistakes.
PMID- 28421876
TI - Congenital tuberculosis: case report and review of the literature.
AB - Congenital tuberculosis is rare, even where tuberculosis (TB) is endemic. A 14
day-old girl presented with a 3-day history of fever and respiratory distress.
Her mother was diagnosed with a disseminated TB infection immediately after the
delivery which was confirmed by a positive TB-polymerase chain reaction (TB-PCR)
and subsequent culture from ascites and sputum. The infant was separated from her
mother at birth. Her chest radiograph showed bilateral miliary nodules.
Congenital TB was strongly suspected because of the symptoms, signs and maternal
TB history, and was confirmed by TB-PCR and culture from the gastric lavage.
Timely administration of standard anti-TB therapy resulted in a good outcome. The
case highlights the importance of maternal TB history and typical miliary pattern
on chest radiography for early diagnosis of congenital or neonatal TB which in
turn facilitates prompt treatment and the prognosis.
PMID- 28421877
TI - Biomarkers in adult posthemorrhagic hydrocephalus.
AB - Posthemorrhagic hydrocephalus is a severe complication following intracranial
hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity
and mortality and serves as an important clinical predictor of adverse outcomes
after intracranial hemorrhage. Currently, no effective medical intervention
exists to improve functional outcomes in posthemorrhagic hydrocephalus patients
because little is still known about the mechanisms of posthemorrhagic
hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic
hydrocephalus pathogenesis would facilitate development of clinical treatments,
this is an active research area. The purpose of this review is to describe recent
progress in elucidation of molecular mechanisms that cause posthemorrhagic
hydrocephalus. What we are certain of is that the entry of blood into the
ventricular system and subarachnoid space results in release of lytic blood
products which cause a series of physiological and pathological changes in the
brain. Blood components that can be linked to pathology would serve as disease
biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are
known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus
progression. These findings suggest that modulation of biomarker expression or
function may benefit posthemorrhagic hydrocephalus patients.
PMID- 28421878
TI - Cerebrovascular injury in cryptococcal meningitis.
AB - Background Cryptococcal meningitis continues to be one of the common causes of
chronic central nervous system infection worldwide. Individuals with cryptococcal
meningitis can occasionally present with small vessel vasculitis causing infarcts
primarily in the basal ganglia, internal capsule, and thalamus. Literature
regarding patterns of cerebrovascular injury among patients with cryptococcal
meningitis is scanty, and outcome following these vascular involvements is
unknown. Aim To study the clinical profile, imaging findings, and details of
vascular territory involved among patients admitted with cryptococcal meningitis
and central nervous system infarct in a tertiary care center from India. And to
compare the outcomes of patients of cryptococcal meningitis with or without
central nervous system infarcts in terms of mortality and morbidity, Methodology
A total of 151 patients with microbiologically proven cryptococcal meningitis
over a time span of 11 years were retrospectively enrolled into the study. Of
these, 66 patients met the inclusion criteria of having appropriate imaging of
the brain. The presence of infarct in the imaging was analyzed by two independent
radiologists. Patterns of central nervous system involvement and types of
vascular injury were ascertained based on radiological parameters. Clinical
parameters and outcomes of patients with and without infarcts were compared.
Results Twenty (13%) of these patients had evidence of central nervous system
infarcts on imaging. The mean age of patients with and without infarcts was 41
years and 38 years, respectively. Male predominance was present among both the
groups. The presence of fever, neck stiffness, positive blood culture, and
hydrocephalus in central nervous system imaging was similar among patients with
or without infarct. Longer duration of illness, low sensorium at the time of
presentation, low Glasgow Coma Scale score, presence of meningeal inflammation,
cryptococcomas, and basal exudates in imaging were higher in patients with
infarct. All the infarcts were of the lacunar type. Sixty percent of the
cerebrovascular infarcts were acute in nature, 50% of these being multiple.
Unilateral infarcts were seen in 70% of the patients. The most common site of
infarct was the basal ganglia, others being distributed over the thalamus,
frontal, temporal, parieto-occipital regions in the descending order. The
presence of neurovascular involvement in the form of infarcts to the risk of
morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively.
Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare
entity. These tend to present as multiple lacunar infarcts. Mortality and
morbidity associated with these patients is higher when compared to patients who
do not have infarcts. This result suggests that vascular injury plays a role in
predicting outcome of patients with cryptococcal meningitis. Future studies are
needed to understand the mechanism by which vascular events (infarcts) occur and
result in poor outcome.
PMID- 28421879
TI - DNA methylation mechanism of intracellular zinc deficiency-induced injury in
primary hippocampal neurons in the rat brain.
AB - OBJECTIVE: To explore Zn2+ deficiency-induced neuronal injury in relation to DNA
methylation, providing valuable data and basic information for clarifying the
mechanism of Zn2+ deficiency-induced neuronal injury. METHODS: Cultured
hippocampal neurons were exposed to the cell membrane-permeant Zn2+ chelator
N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 MUM), and to TPEN
(2 MUM) plus ZnSO4 (5 MUM) for 24 hours. We analyzed intracellular Zn2+ levels,
neuronal viability, and protein/mRNA levels for DNA (cytosine-5)
methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha
(DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor
(BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated
neurons. RESULTS: We found that exposure of hippocampal neurons to TPEN (2 MUM)
for 24 hours significantly reduced intracellular Zn2+ concentration and neuronal
viability. Furthermore, DNMT3a, DNMT1, BDNF, and GADD45b protein levels in TPEN
treated neurons were significantly downregulated, whereas MeCP2 levels were, as
expected, upregulated. In addition, DNMT3a and DNMT1 mRNA levels in TPEN-treated
neurons were downregulated, while MeCP2, GADD45b, and BDNF mRNA were largely
upregulated. Addition of ZnSO4 (5 MUM) almost completely reversed the TPEN
induced alterations. CONCLUSION: Our data suggest that free Zn2+ deficiency
induced hippocampal neuronal injury correlates with free Zn2+ deficiency-induced
changes in methylation-related protein gene expression including
DNMT3a/DNMT1/MeCP2 and GADD45b, as well as BDNF gene expression.
PMID- 28421880
TI - Interactive dynamics among therapist interventions, therapeutic alliance and
metacognition in the early stages of the psychotherapeutic process.
AB - OBJECTIVE: Several authors have identified a bidirectional link between patient
metacognitive functioning and the therapeutic alliance. Specifically,
metacognition might be enhanced by a positive alliance with the clinician,
whereas metacognitive deficits might impede the alliance. Interestingly, the
therapist's technical interventions might influence both therapeutic alliance and
metacognitive functioning. However, little is known about the interactions
between these dimensions. The aim of the present study is to explore these
interactions more fully in the earliest phase of the therapeutic process. METHOD:
Participants included 24 patients and 12 therapists in training. The
Metacognition Assessment Scale-Revised, Collaborative Interaction Scale, and
Psychodynamic Intervention Rating Scale were employed in the first three sessions
of psychotherapy. RESULTS: Sequential analyses revealed that different therapist
interventions co-occurred with three different levels of the therapeutic
alliance: A first level characterized by a positive collaboration, a second
characterized by a neutral collaboration, and a third characterized by ruptures.
Importantly, the patient's metacognitive functioning was found to mediate the
relationship between the therapeutic intervention and the therapeutic alliance in
the positive and neutral levels of collaboration but not in the ruptures one.
CONCLUSIONS: These findings suggest that a specific interdependence exists among
the therapeutic alliance, technical intervention, and metacognitive functioning.
Clinical or methodological significance of this article: From a methodological
standpoint, the originality of the present study lies in the combination of an
interactionist approach, which conceives process factors as interrelated
dimensions interacting in non-additive and often nonlinear ways, with analyses at
both micro- and macro-analytic levels (i.e., sequential and mediation analyses).
From a theoretical standpoint, findings of the present study indicate that
specific therapist's interventions are related to specific levels of the
therapeutic alliance (i.e., positive, neutral and negative), hence providing
crucial insights into the clinical understanding of the psychotherapy process.
PMID- 28421881
TI - Factors pivotal for designing of nanoantimicrobials: an exposition.
AB - Understanding the interplay between bacterial pathogens and antimicrobials is a
key to realize the control over infections causing morbidity and mortality. An
important current issue of contemporary medicine and microbiology is the search
for new strategies for adequate therapy of infectious diseases associated with
rapidly emerging multidrug-resistant (MDR) pathogens. Recently, a great deal of
progress has been made in the field of nanobiotechnology towards the development
of various nanoantimicrobials (NAMs) as novel therapeutic solution. Current
microbiological studies, employing either synthetic antibiotics or natural
antimicrobial, have demonstrated the ability of NAMs to tackle the issue of MDR
by reverting the mechanisms of resistance. The present review critically
discusses the various factors that can contribute to modulate the effects of NAMs
on microbes. It includes essential features of NAMs including but not limited to
composition, surface charge, loading capacity, size, hydrophobicity/philicity,
controlled release and functionalization. In contrast, how microbial structural
differences, biofilm formation, persister cells and intracellular pathogens
contribute towards sensitivity or resistance towards antimicrobials is
comprehensively analysed. These multilateral factors should be considered
earnestly in order to make NAMs a successful alternative of the conventional
antibiotics.
PMID- 28421882
TI - Inhibition of HER3 activation and tumor growth with a human antibody binding to a
conserved epitope formed by domain III and IV.
AB - Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged
as relevant target for antibody-mediated tumor therapy. Here, we describe a novel
human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and
parts of domain IV of the extracellular region of HER3, conserved between HER3
and mouse ErbB3. An affinity of 11 nM was determined for the monovalent
interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with
subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50
values in the low picomolar range (27 - 83 pM). The antibody competed with
binding of heregulin to HER3-expressing cells, efficiently inhibited
phosphorylation of HER3 as well as downstream signaling, and induced receptor
internalization and degradation. Furthermore, IgG 3-43 inhibited heregulin
dependent proliferation of several HER3-positive cancer cell lines and heregulin
independent colony formation of HER2-overexpressing tumor cell lines.
Importantly, inhibition of tumor growth and prolonged survival was demonstrated
in a FaDu xenograft tumor model in SCID mice. These findings demonstrate that by
binding to the membrane-proximal domains III and IV involved in ligand binding
and receptor dimerization, IgG 3-43 efficiently inhibits activation of HER3,
thereby blocking tumor cell growth both in vitro and in vivo.
PMID- 28421883
TI - CTSA Institution Responses to Proposed Common Rule Changes: Did They Get What
They Wanted?
AB - In 2015, the U.S. Department of Health and Human Services (HHS) and 15 other
federal departments and agencies proposed revisions to the Federal Policy for the
Protection of Human Subjects. In this Notice of Proposed Rulemaking (NPRM), the
departments sought to strengthen, modernize, and make more effective human
subjects regulations while reducing administrative burden, delay, and ambiguity.
We reviewed public comments from National Institutes of Health (NIH)-funded
Clinical and Translational Science Awards (CTSA) institutions on key provisions
of the NPRM to understand how the proposed changed were received at research
intensive institutions. CTSA institutions responding to the proposed rule were
predominantly opposed to the major proposals, including proposed changes to the
treatment of de-identified biospecimens, demonstrating a lack of support from
academic medical centers. In January 2017, a Final Rule was issued. We compare
the Final Rule to what was proposed.
PMID- 28421884
TI - Children's Decision-Making Involvement About Research Participation: Associations
With Perceived Fairness and Self-Efficacy.
AB - The primary objective of this study was to examine the associations of children's
involvement in decisions about research participation with their perceptions of
the decision-making process and self-efficacy. Participants were children (ages 8
17) who enrolled in research studies in the prior 2 months. Children completed a
questionnaire that yielded three decision-making involvement subscales:
Researcher Engages Child, Researcher Supports Autonomy, and Child Participates.
Children reported on fairness of the decision-making process and health-related
decision self-efficacy. After adjusting for age, higher scores on Researcher
Engages Child were associated with greater self-efficacy, and higher scores on
Researcher Supports Autonomy were associated with greater perceived fairness.
These data underscore the potential importance of researcher-child interactions
about research participation when assent is sought, including proactively
involving children in the decision by asking for their opinions and communicating
their central role in the decision, which are likely to be more meaningful to
children than receiving information or signing a form.
PMID- 28421885
TI - Recognizing Risk and Vulnerability in Research Ethics: Imagining the "What Ifs?"
AB - Research ethics committees (RECs) may misunderstand the vulnerability of
participants, given their distance from the field. What RECs identify as the
vulnerabilities that were not adequately recognized in protocols and how they
attempt to protect the perceived vulnerability of participants and mitigate risks
were examined using the response letters sent to researchers by three university
based RECs. Using a critical qualitative method informed by feminist ethics, we
identified an overarching theme of recognizing and responding to cascading
vulnerabilities and four subthemes: identifying vulnerable groups, recognizing
potentially risky research, imagining the "what ifs," and mitigating perceived
risks. An ethics approach that is up-close, as opposed to distant, is needed to
foster closer relationships among participants, researchers, and RECs and to
understand participant vulnerability and strength better.
PMID- 28421888
TI - Instructions to Prospective Authors by Indian Biomedical Journals: An Opportunity
to Promote Responsible Conduct of Research.
AB - Journals provide instructions to prospective authors to facilitate the process of
manuscript publication. The information provided under such instructions could be
a potential opportunity to promote responsible conduct of research (RCR). We
analyzed 74 Indian biomedical journals for the type of information provided in
the "instructions to authors" section and adherence to the International
Committee of Medical Journal Editors (ICMJE) recommendations. Among the 71
journals that had an "instructions to authors" section, 53 journals adhered to
ICMJE recommendations. We discuss sections of the ICMJE recommendations detailed
by Indian biomedical journals under the "instructions to authors" section and
emphasize components that require greater exposure.
PMID- 28421887
TI - Preferences for the Return of Individual Results From Research on Pediatric
Biobank Samples.
AB - Discussions about disclosing individual genetic research results include calls to
consider participants' preferences. In this study, parents of Boston Children's
Hospital patients set preferences for disclosure based on disease preventability
and severity, and could exclude mental health, developmental, childhood
degenerative, and adult-onset disorders. Participants reviewed hypothetical
reports and reset preferences, if desired. Among 661 participants who initially
wanted all results (64%), 1% reset preferences. Among 336 participants who
initially excluded at least one category (36%), 38% reset preferences.
Participants who reset preferences added 0.9 categories, on average; and their
mean satisfaction on 0 to 10 scales increased from 4.7 to 7.2 ( p < .001). Only
2% reduced the number of categories they wanted disclosed. Findings demonstrate
the benefits of providing examples of preference options and the tendency of
participants to want results disclosed. Findings also suggest that preference
setting models that do not provide specific examples of results could
underestimate participants' desires for information.
PMID- 28421889
TI - Overall Assessment of Human Research and Ethics Committees in the United Arab
Emirates.
AB - Growing demand for human health research in the United Arab Emirates (UAE) has
prompted the need to develop a robust research ethics oversight. Examination of
the structure, function, and practices of the human research ethics committees
(HRECs), followed by evaluation of standards for measuring research output, was
conducted. Results indicate that among the HRECs, 90% followed International
Council for Harmonization-Good Clinical Practice guidelines, 66.6% have been in
operation for more than 5 years, 95% reviewed proposals within 8 weeks, and 56%
reviewed for scientific merit apart from ethics. However, systems to recognize
accomplishments of researchers, funding transparency, and adverse event reporting
were deployed in less than 30% of all HRECs. Research was incorporated into the
vision and mission statements of many (65%) organizations. Research publications,
collaborations, and recognitions were used to measure research output and report
key performance indicators. In spite, resources to generate research output such
as dedicated budget (20%), support staff (20%), and continuous training and
mentoring program for medical residents (15%) and HREC members (25%) were somehow
lacking. HREC structure and operations in the UAE are similar to other regions of
the world. Systems to conduct research and report outcomes are defined in the
UAE. Regulatory legislation and allocation of resources to support the clinical
research enterprise will not only help to meet growing demand for clinical trials
but also transform the quality of patient care in the UAE. It is anticipated that
the results of this study will benefit investigators, regulators, pharmaceutical
sponsors, and the policy makers in the region.
PMID- 28421890
TI - Inmate Health Care Provided in an Emergency Department.
AB - The United States has the highest rate of incarceration in the world. Many
correctional facilities have outsourced the medical care for this population that
often presents with complex health issues. This study evaluates the reasons that
inmates present to an emergency department (ED) and compares them to the general
population ED visits. The most common presenting complaints were trauma (16.8%),
abdominal pain (13.5%), chest pain (9.0%), and self-injury (8.7%). These
presenting complaints differed significantly from those of the general population
(abdominal pain [8.1%] and chest pain [5.2%]). Inmate-patients seen in the ED
presented with a significantly higher frequency of trauma, 16.8% versus
approximately 1.5%.
PMID- 28421891
TI - Truth Be Told: Evaluation of a Narrative and Skills Intervention in Two Women's
Prisons.
AB - This article describes the evaluation of a narrative and skills intervention to
enable women to come to terms with their offenses, tell the truth, and then work
to deal with the emotions and issues surrounding their offenses, in two southern
U.S. women's prisons. The intervention involved skills building in communication,
community building, creativity, and caring for the self, using narrative writing,
speaking, and movement. There was broad agreement that the intervention had
multiple positive impacts, including insight into factors that lead to
incarceration, comfort with selves and better ability to express themselves,
restorative justice (ability to understand the situation of others, understanding
the impact on themselves and their families), better relationships with other
inmates, and understanding the challenges that may lead to recidivism. Findings
are consistent with the importance of "confession" and the importance of
narrative in traumatic life situations in bringing resolution.
PMID- 28421892
TI - Editor's Letter.
PMID- 28421893
TI - Journal of Correctional Health Care.
PMID- 28421894
TI - How learning analytics can early predict under-achieving students in a blended
medical education course.
AB - AIM: Learning analytics (LA) is an emerging discipline that aims at analyzing
students' online data in order to improve the learning process and optimize
learning environments. It has yet un-explored potential in the field of medical
education, which can be particularly helpful in the early prediction and
identification of under-achieving students. The aim of this study was to identify
quantitative markers collected from students' online activities that may
correlate with students' final performance and to investigate the possibility of
predicting the potential risk of a student failing or dropping out of a course.
METHODS: This study included 133 students enrolled in a blended medical course
where they were free to use the learning management system at their will. We
extracted their online activity data using database queries and Moodle plugins.
Data included logins, views, forums, time, formative assessment, and
communications at different points of time. Five engagement indicators were also
calculated which would reflect self-regulation and engagement. Students who
scored below 5% over the passing mark were considered to be potentially at risk
of under-achieving. RESULTS: At the end of the course, we were able to predict
the final grade with 63.5% accuracy, and identify 53.9% of at-risk students.
Using a binary logistic model improved prediction to 80.8%. Using data recorded
until the mid-course, prediction accuracy was 42.3%. The most important
predictors were factors reflecting engagement of the students and the consistency
of using the online resources. CONCLUSIONS: The analysis of students' online
activities in a blended medical education course by means of LA techniques can
help early predict underachieving students, and can be used as an early warning
sign for timely intervention.
PMID- 28421895
TI - Metastatic Pulmonary Angiosarcoma Presenting With Bilateral Secondary Spontaneous
Pneumothoraces.
AB - BACKGROUND: Spontaneous pneumothorax (SP) is uncommon and can present as a
primary disease process or as a result of underlying lung pathology. Several
parenchymal lung diseases, such as malignancy, are known to cause SP. One such
malignancy, angiosarcoma, has a high propensity to metastasize to the lung and
present as cavitary and cystic lesions. CASE: We present a case of a 76-year-old
male diagnosed with angiosarcoma of the scalp that was found to have extensive
cystic pulmonary metastatic lesions. Soon after his initial diagnosis, he
presented with severe respiratory distress secondary to a spontaneous left-sided
pneumothorax. After intubation and left-sided chest tube placement, the patient
developed a right-sided tension pneumothorax requiring emergent chest tube
placement. CONCLUSION: Cutaneous angiosarcoma is a rare malignancy that
frequently metastasizes the lung. Spontaneous pneumothorax can be the presenting
manifestation of the disease and often results in respiratory failure.
PMID- 28421896
TI - Anosognosia and Its Relation to Psychiatric Symptoms in Early-Onset Alzheimer
Disease.
AB - BACKGROUND: We investigated differences in the prevalence of anosognosia and
neuropsychiatric symptoms (NPSs) characteristics according to disease severity in
patients with early-onset Alzheimer disease (EOAD). METHODS: We recruited 616
patients with EOAD. We subdivided participants into 2 groups based on the
presence or absence of anosognosia and then again by Clinical Dementia Rating
(CDR) scale. We compared the differences in the Neuropsychiatric Inventory (NPI)
scores according to anosognosia and disease severity. RESULTS: The percentage of
patients with anosognosia in each CDR group steadily increased as the CDR rating
increased (CDR 0.5 8.6% vs CDR 1 13.6% vs CDR 2 26.2%). The NPI total score was
significantly higher in patients with anosognosia in the CDR 0.5 and 1 groups; by
contrast, it had no association in the CDR 2 group. Frontal lobe functions were
associated with anosognosia only in the CDR 0.5 and 1 groups. After
stratification by CDR, in the CDR 0.5 group, the prevalence of agitation ( P =
.040) and appetite ( P = .013) was significantly higher in patients with
anosognosia. In the CDR 1 group, patients with anosognosia had a significantly
higher prevalence of delusions ( P = .032), hallucinations ( P = .048), and sleep
disturbances ( P = .047). In the CDR 2 group, we found no statistical difference
in the frequency of symptoms between patients with and without anosognosia.
CONCLUSION: These results confirm that the prevalence of anosognosia as well as
the individual NPS and cognitive functions associated with it differ according to
EOAD severity.
PMID- 28421897
TI - Negative Bias in the Perception and Memory of Emotional Information in Alzheimer
Disease.
AB - BACKGROUND: There is some controversy about the ability of patients with
Alzheimer disease (AD) to experience and remember emotional stimuli. This study
aims to assess the emotional experience of patients with AD and the existence of
emotional enhancement of memory. We also investigated the influence of affective
state on these processes. METHODS: Sixty pictures from the International
Affective Picture System were administered to 106 participants (72 patients with
AD and 54 controls). Participants performed immediate free recall and recognition
tasks. Positive and Negative Affect Schedule was used to assess the participants'
current affect. RESULTS: Patients identified the valence of unpleasant pictures
better than of others pictures and experienced them as more arousing. Patients
and controls recalled and recognized higher number of emotional pictures than of
neutral ones. Patients discriminated better the unpleasant pictures. A mood
congruent effect was observed on emotional experience but not on memory. Positive
affect was associated with better immediate recall and with a more liberal
response bias. CONCLUSION: Patients with AD can identify the emotional content of
the stimuli, especially of the unpleasant ones, and the emotional enhancement of
memory is preserved. Affective state does not explain the differences in the
processing and memory of emotional items between patients and controls.
PMID- 28421899
TI - Prolapse of the bladder through a vesicovaginal fistula.
PMID- 28421900
TI - The magnitude and factors related to facility-based maternal mortality in
Mozambique.
AB - Facility-based maternal mortality remains an important public health problem in
Mozambique. A number of factors associated with health system functioning can be
described behind the occurrence of these deaths. This paper aimed to evaluate the
magnitude of the health facility-based maternal mortality, its geographical
distribution and to assess the health facility factors implicated in the
occurrence of these deaths. A secondary analysis was done on data from the survey
on maternal health needs performed by the Ministry of Health of Mozambique in
2008. During the study period 2.198 maternal deaths occurred out of 312.537
deliveries. According to the applied model the availability of Maternal and Child
Health (MCH) nurses performing Emergency Obstetric Care functions was related to
the reduction of facility-based maternal mortality by 40%. No significant effects
were observed for the availability of medical doctors, surgical technicians and
critical delivery room equipment. Impact statement Is largely known that the
availability of skilled attendants assisting every delivery and providing
Emergency Obstetric Care services during the pregnancy, labor and Childbirth is
key for maternal mortality reduction. This study add the differentiation on the
impact of different cadres of health services providers working on maternal and
child health services on the facility based maternal mortality. In this setting
the study proven the high impact of the midlevel skilled maternal and child
health nurses on the reduction of maternal mortality. Another important add from
this study is the use of facility based maternal mortality data to inform the
management process of maternal healthcare services. The findings from this study
have potential to impact on the decision of staffing prioritization in setting
like the study setting. The findings support the policy choice to improve the
availability of maternal and child health nurses.
PMID- 28421898
TI - Targeting the nuclear RNA exosome: Poly(A) binding proteins enter the stage.
AB - Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually
all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is
guided to its RNA targets by adaptor proteins that enable substrate recognition.
Recently, the discovery of the 'Poly(A) tail exosome targeting (PAXT)' connection
as an exosome adaptor to human nuclear polyadenylated transcripts has relighted
the interest of poly(A) binding proteins (PABPs) in both RNA productive and
destructive processes.
PMID- 28421901
TI - BMI at early puerperium: Body image, eating attitudes and mood states.
AB - The present study was aimed to verify if body weight could influence self
perception, in terms of body image, mood states, dissatisfaction with physical
appearance and risk of eating disorders. In particular, we evaluated the
differences between women of normal weight vs. overweight and obese during the
delicate phase of puerperium to verify if there were different emotional
structures, linked to BMI. Thirty-two women, 16 normal-weight and 16 overweight
or obese, belonging to the Department of Obstetrics and Gynaecology of the
University Hospital, were individually interviewed. The Body Uneasiness Test
(BUT), the Eating Disorder Inventory (EDI) and the Profile of Mood States (POMS)
were used for the evaluation. Findings showed that the BMI in puerperium is
significantly correlated to mood states and body perception. Furthermore,
significant differences emerged in eating attitudes and behaviours, in specific
aspects related to the weight gain phobia and the body shape perception, symptoms
classically associated with the risk of developing an eating disorder.
PMID- 28421902
TI - The role of ovarian reserve markers in prediction of clinical pregnancy.
AB - To evaluate the role of ovarian reserve markers in the prediction of clinical
pregnancy and embryo transfer accomplishment among poor responder IVF applicants.
304 female poor responder IVF applicants were included in this prospective cohort
study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF
outcomes were compared in pregnant and non-pregnant groups as well as in ET vs.
non-ET groups. The number of retrieved oocytes was significantly correlated
positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH
and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and
<25%/>75%) were statistically significant. Mean serum levels for AMH were
significantly lower in the non-ET group. Our findings seem to indicate that day 3
AMH values can predict ET accomplishment with a sensitivity of 96% and a
specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF
results among poor responder IVF applicants. Impact statement Various cut-off
values have been determined for day 3 serum AMH values. These values help to
determine the groups that are expected to give normal, high or low response to
stimulation and decide the treatment options. In contrast to other groups of
patients, poor responders cannot reach the embryo transfer stage for several
reasons. These are; absence of a mature oocyte after oocyte pick-up,
fertilisation failure without male factor or poor embryo quality. In the present
study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in
poor responder patients was determined with a sensitivity of 96%. Additionally,
clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH
values. It is important to clarify the embryo transfer success of poor responder
patients prior to expected treatment success. Pre-treatment counselling for these
patients would lessen the disappointment that may develop after treatment. The
cost-effectiveness of treatments below these AMH values can be determined by
further studies.
PMID- 28421903
TI - Expression of matrix metalloproteinase-9 and its substrate level in patients with
premature rupture of membranes.
AB - In this study, 30 case of patients with full-term premature membrane rupture and
another 30 cases of full-term delivered subject without premature rupture of
membranes (PROM) were selected to explore the relationship between premature
membrane rupture with matrix metalloproteinase 9 (MMP-9) and its substrate level.
Results showed the plasma zinc, MMP-9 in serum and amniotic fluid increased in
patients with PROM; their type IV collagen in serum and foetal membrane
decreased. Increased Zinc ion concentration results in increased concentration of
MMP-9, a zinc-dependent enzyme; the degradation of type IV collagen by MMP-9
might be the potential mechanism of premature rupture of membranes in full-term
pregnant women.
PMID- 28421904
TI - Effects of 1alpha, 25-dihydroxyvitamin D3 on programmed cell death of Ishikawa
endometrial cancer cells through ezrin phosphorylation.
AB - This study investigated the effects of 1alpha, 25-dihydroxyvitamin D3-induced
cell death and its underlying molecular mechanisms in Ishikawa endometrial
carcinoma cells. The effects of 1alpha, 25-dihydroxyvitamin D3 on Ishikawa cells
were examined by 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide,
thiazolyl blue (MTT) assay. 1alpha, 25-dihydroxyvitamin D3 was shown to induce
programmed cell death in Ishikawa endometrial carcinoma cells by activation of
caspase-3 and caspase-9, along with elevation of Bcl-2 and Bcl-xL. Cell viability
was reduced by 1alpha, 25-dihydroxyvitamin D3 in a concentration-dependent manner
up to 2.5 MUM. In addition, ezrin phosphorylation increased with the 1alpha, 25
dihydroxyvitamin D3 concentration (0-0.5 MUM). The protein level of caspase-9 was
increased by 1alpha, 25-dihydroxyvitamin D3 up to 0.5 MUM. This is the first
report regarding the efficacy and molecular mechanisms underlying the effects of
1alpha, 25-dihydroxyvitamin D3 in endometrial cancer cells. Our findings indicate
that 1alpha, 25-dihydroxyvitamin D3 induces endometrial cancer cell death in a
concentration-dependent manner. Impact statement Up to date, there is no report
about the efficacy and molecular underlying mechanisms on the effect of vitamin
D3 in endometrial cancer cells. Our findings indicate that 1alpha, 25
dihydroxyvitamin D3. which is an active metabolite of vitamin D3, induces
Ishikawa endometrial cancer cell death in a concentration-dependent manner by
activation of caspase-3 and -9, along with elevation of Bcl-2 and Bcl-xL. In
addition, the same concentration of 1alpha, 25-dihydroxyvitamin D3 that provoked
apoptotic signals caused phosphorylation of ezrin at threonine 567 in a VDR
dependent manner. This study suggests that 1alpha, 25-dihydroxyvitamin D3 within
the optimal range (0.5 uM) would induce apoptosis through Fas-ezrin-caspase-3,
8, -9 signalling axis which may be a critical cell death regulator in Ishikawa
endometrial cancer cell. Further study will be more interesting to address
molecular connections or prove this critical optimal concentration range of
vitamin D.
PMID- 28421905
TI - Ultrasonic elastography exploration of the foetal brain: A case of atypical
choroid plexus papilloma.
PMID- 28421906
TI - The role of para-aortic lymphadenectomy in stage IIIC endometrial cancer: A
single-institute study.
AB - The therapeutic value of para-aortic lymphadenectomy (PAL) in women with
endometrial cancer (EC) remains uncertain. We retrospectively analysed 25
patients with stage IIIc EC (17 stage IIIC1; 8 IIIC2) who were treated in our
institution. All subjects had undergone pelvic lymphadenectomies in which para
aortic nodes were sampled, or removed only when these nodes were enlarged.
Sampling of para-aortic nodes or PAL was performed in all patients with stage
IIIC2 disease and one of 17 with stage IIIC1 disease. Para-aortic lymph nodes
were the most frequent site of recurrence in stage IIIC1 patients, but no such
recurrences occurred in stage IIIC2 patients. Overall survival tended to be
shorter in stage IIIC1 patients than stage IIIC2 patients. Our findings indicate
that PAL improves the outcomes of patients with EC and high risk of para-aortic
lymph node metastasis, such as those with positive pelvic lymph nodes or
enlargement of para-aortic lymph nodes. Impact statement Para-aortic lymph node
(PALN) metastases are important prognostic factors in endometrial cancer. Overall
survival of patients with stage IIIC1 disease is generally longer than for those
with stage IIIC2 disease. Retrospective studies - but no prospective studies -
have suggested that para-aortic lymphadenectomy (PAL) provides a survival
benefit. In our institution, we had performed PAL or para-aortic sampling for
patients with enlarged PALNs; therefore, as most IIIC1 patients had no enlarged
PALNs, they underwent pelvic lymphadenectomy only, whereas all IIIC2 patients had
enlarged PALNs and underwent pelvic lymphadenectomy and PAL or PALN sampling in
addition to pelvic lymphadenectomy. However, under this policy, survival of stage
IIIC1 patients was not better than for stage IIIC2 patients. Our retrospective
study indicates a survival benefit for PAL in patients with pelvic node-positive
or enlarged PALN. PAL warrants a prospective randomised trial to see whether it
should be a standard treatment in these patients.
PMID- 28421907
TI - A review of the open laparoscopic Hasson technique and retrieval of adnexal
specimen via umbilicus.
AB - Laparoscopic entry techniques vary amongst surgeons and gynaecologists, with
gynaecologists favouring Veress needle entry. Recent RCOG/BSGE recommendations
have recommended retrieval of ovarian masses via the umbilical port with
resultant less postoperative pain and a faster retrieval time than with retrieval
through lateral ports of the same size. This is a prospective observational study
reviewing the Hasson entry technique and the introduction of retrieval of
specimens via the umbilicus in patients scheduled for a laparoscopy procedure at
our day surgery unit. We found no immediate or major surgical complications and
all specimens were successfully retrieved through the umbilicus. Pain scores were
low. We recommend the technique for extirpative gynaecological surgery. Impact
Statement This study confirms that conversion from the closed Veress to the open
Hasson technique is achievable in a university hospital setting. Operator
confidence during the learning phase is enhanced by the use of ultrasound to
locate and measure the depth of the umbilical ligament. Retrieval of benign
adnexal specimens through the umbilicus was very satisfactory.
PMID- 28421908
TI - Extravasating uterine pseudoaneurysm: A rare cause of postpartum haemorrhage.
AB - Postpartum haemorrhage (PPH) remains one of the leading causes of maternal death
worldwide and can be classified as either immediate (primary) or delayed
(secondary) according to the onset time - before or after 24 hours postpartum.
Uterine pseudoaneurysm is a rare cause of PPH that has been suggested to arise
from abnormal vascular regression and a recurrent vascular healing state, such as
a vascular stricture and relaxation with thrombin deposits after placental
expulsion. With advances in multidetector computed tomography, 3D-computed
tomography with angiography can aid in identifying the location and originating
vessels of the pseudoaneurysm via fast and clear 3D images. Once a bleeding
pseudoaneurysm is diagnosed as the cause of PPH, conservative management is
frequently unsuccessful in controlling bleeding. Transcatheter uterine arterial
embolisation appears to be the treatment of choice in haemodynamically stable
women.
PMID- 28421909
TI - Management of intra-abdominally translocated contraceptive devices, is surgery
the only way to treat this problem?
AB - This study was a multi-centre retrospective review of patients with uterine
perforation caused by intrauterine contraceptive devices (IUDs). A total of 15
patients were registered, in a seven year period. Among them, five were
asymptomatic and the rest were symptomatic. Asymptomatic patients were managed
conservatively, except in one case in which the patient requested surgery because
she also wanted a tubal ligation. Symptomatic patients all underwent surgery. All
the surgeries were elective and all the surgical procedures were initiated
laparoscopically. There were seven complications in the surgically managed group:
conversion to laparotomy (n = 3), bowel injury (n = 2), bladder injury (n = 1),
and wound infection (n = 1). Mild and severe adhesions (81.8%), and abscess
(18.1%) formation related to translocated IUD (TIUD) were observed during
surgery. All the patients were uneventful at 1 to 5 years of follow-up. A TIUD,
by causing adhesions, complicates future laparoscopic surgery and increases the
likelihood of conversion to laparotomy. While surgery is indicated to prevent
TIUD-induced adhesive complications, it may also be the cause of both adhesions
and complications, resulting in a vicious cycle. Some asymptomatic women,
especially elderly patients with comorbidities, may not need or may be better
managed without treatment. Impact statement In this study we try to find an
answer for the question of "Should removal of a translocated intrauterine
contraceptive device (TIUD) routinely be performed even if patients are
asymptomatic?" From only the theoretical point of view there were some reports
supporting conservative management in asymptomatic patients. The other studies
addressing this issue were case reports including few patients with a short-term
follow-up. The novelties of the present study include multi-centre design,
detailed clinical and surgical information about the patients and the long period
of follow-up. Most clinicians have limited experiences in managing TIUD because
perforation is a rare event. So it can be difficult to know exactly what the
surgeon will encounter intraoperatively. We undertook this study with the aim of
providing a perspective about patients with TIUD for those faced with this
situation. This is a descriptive study reporting 15 cases of TIUDs and
management. Asymptomatic patients were managed conservatively, and symptomatic
patients were operated. There are important implications resulting from this
study that in asymptomatic patients leaving the IUD in place may be a reasonable
option, mostly as the risk of surgical intervention is quite high with a high
rate of complications with surgical management.
PMID- 28421910
TI - Multi-step treatment for acquired alexia and agraphia (part II): a dual-route
error scoring system.
AB - Dual-route neuropsychological models posit two distinct but interrelated pathways
for reading and writing: the lexical and the sublexical. Individuals with
reading/writing deficits often rely on the combined power of the integrated
system to perform print-processing tasks. The resultant errors reflect varying
degrees of lexical and sublexical accuracy in a single production; however, no
system presently exists to analyze errors robustly in both routes. The goal of
this project was to develop a system that simultaneously, quantitatively, and
qualitatively captures changes in lexical and sublexical errors following
treatment. Errors are evaluated hierarchically in both routes according to
proximity to a target. This dual-route error scoring (DRES) system was developed
using data from a novel treatment study for eight patients with acquired
alexia/agraphia; a computerised version of the system was also developed (ADRES).
Repeated-measures multivariate analyses of variance and post hoc analyses
revealed significant dual-route treatment effects. Qualitative analyses revealed
unique patterns of change across participants, reflecting the benefits of error
evaluation beyond a binary correct/incorrect judgment. Finally, categorical error
shifts were observed via group-level analysis. The results of this study indicate
that treatment-induced evolution of reading/writing can be meaningfully and
comprehensively represented by this novel scoring system.
PMID- 28421911
TI - Sleep Habits and Nighttime Texting Among Adolescents.
AB - The aim of this study was to examine sleep habits (i.e., bedtimes and rising
times) and their association with nighttime text messaging in 15- to 17-year-old
adolescents. This cross-sectional study analyzed data from a web-based survey of
adolescent students attending secondary schools in southern Sweden ( N = 278, 50%
female). Less than 8 hr of time in bed during school nights was significantly
associated with more sleep difficulties, wake time variability on school days and
weekends, daytime tiredness, and less enjoyment at school (all ps < .05). Sending
and/or receiving text messages (Short Message Service [SMS]) at night was
significantly associated with later bedtimes, shorter time in bed, daytime
tiredness during school, and irregular sleep habits ( p < .05). These findings
highlight the importance of regular, consistent sleep habits and the problems
associated with sleeping with a cell phone in the bedroom.
PMID- 28421912
TI - A Survey of School Nurse Emergency Preparedness 2014-2015.
AB - Well-prepared school nurses are more likely to handle emergencies properly. Thus,
assessing crisis management preparedness is important. In August 2014, a
questionnaire was sent to 275 nurses in a large Texas school system to collect
data about nurse and school characteristics, emergency frequency and management,
and equipment availability. Completed surveys (201, 73%) were analyzed. Fisher's
exact test was used to evaluate comparisons among nurses' confidence levels,
school characteristics, emergencies, and medical emergency response plans (MERP).
Logistic regression was used to estimate associations between characteristics and
nurses reporting less confidence. Most respondents were experienced nurses.
Shortness of breath was the most common event faced. Odds of less confidence were
significantly higher among nurses with <5 years' experience, working at
elementary schools, schools without a MERP or where it was not practiced, or
caring for <10 schoolchildren weekly. Overall, recommended emergency management
guidelines were met.
PMID- 28421913
TI - Type VI Secretion Systems of Erwinia amylovora Contribute to Bacterial
Competition, Virulence, and Exopolysaccharide Production.
AB - The type VI secretion system (T6SS) plays a major role in mediating
interbacterial competition and might contribute to virulence in plant pathogenic
bacteria. However, the role of T6SS in Erwinia amylovora remains unknown. In this
study, 33 deletion mutants within three T6SS clusters were generated in E.
amylovora strain NCPPB1665. Our results showed that all 33 mutants displayed
reduced antibacterial activities against Escherichia coli as compared with that
of the wild-type (WT) strain, indicating that Erwinia amylovora T6SS are
functional. Of the 33 mutants, 19 exhibited reduced virulence on immature pear
fruit as compared with that of the WT strain. Among them, 6, 1, and 12 genes
belonged to T6SS-1, T6SS-2, and T6SS-3 clusters, respectively. Interestingly,
these 19 mutants also produced less amylovoran or levan or both. These findings
suggest that E. amylovora T6SS play a role in bacterial competition and virulence
possibly by influencing exopolysaccharide production.
PMID- 28421914
TI - Seeing the forest but not the trees: Heterogeneity in community size effects in
Canadian ice hockey players.
AB - The community size effect (or birthplace effect) suggests that high-performance
athletes are less likely to emerge from regions with population sizes that are
very small or very large. However, previous research on elite Canadian ice hockey
players has not considered the influence of intra-national regional variation of
population distributions with respect to community size effects. Therefore, the
purpose of the current study was to test the heterogeneity of the community size
effect between Canadian National Hockey League draftees (2000-2014: n = 1505),
from 7 provincial regions within Canada (i.e., British Columbia, Alberta,
Saskatchewan, Manitoba, Ontario, Quebec and the Atlantic Provinces). The
proportion of athletes in the 9 census population categories were compared to the
national and regional general population distributions in the census categories.
Results suggest variability of community size effects between the 7 provincial
regions within Canada, with only the province of Ontario demonstrating a
community size effect congruent with effects reported in previous research. Using
regional general population distributions as the comparator to athlete
populations changed the direction, meaningfulness and magnitude of community size
effects. In conclusion, elite ice hockey player community size effects may not be
generalisable to all regions within Canada.
PMID- 28421915
TI - Use of a Modified Classic BT Shunt in a Patient With Multiple Conduit
Obstructions With Positive Lupus Anticoagulant.
AB - The use of a right ventricle-to-pulmonary artery conduit has re-emerged as a
popular alternative to a systemic artery-to-pulmonary artery shunt in the Norwood
procedure. Both proximal obstruction secondary to dynamic compression and distal
obstruction at the anastomosis site with the pulmonary arteries are well
described. In an effort to prevent complications, a technique where in the
conduit is placed through the entire full thickness, or dunked, through the RV
free wall has been described. We report a case of a patient with HLHS and
positive lupus anticoagulant who developed recurrent conduit obstructions. The
"Sano" was abandoned in favor of an autologous source of pulmonary blood flow-the
modified Blalock-Taussig shunt using the "turn down" of the carotid artery.
PMID- 28421916
TI - Mucopolysaccharidoses Causing Valvular Heart Disease: Report and Review of
Surgical Management.
AB - Mucopolysaccharidosis type I is a genetic disorder with impaired
glycosaminoglycan degradation. Cardiac pathologic involvement in this subset of
patients is predominantly valvular heart disease. Valvular heart disease seen in
these patients will most likely require surgical intervention in their lifetime.
Only a limited amount of reports are dedicated to the cardiac surgical management
of mucopolysaccharidoses. We present the case of a 32-year-old female with Hurler
Scheie syndrome who required multiple valve replacements due to progression of
valvular dysfunction and decline in the quality of life. Multidisciplinary
evaluation and discussion early are crucial for quality of life optimization in
this cohort of patients.
PMID- 28421918
TI - Number of mature applicants drops dramatically.
AB - The government is storing up problems for the future after it emerged
applications to nursing programmes from mature students have dropped by more than
one quarter, says the RCN.
PMID- 28421917
TI - The money doesn't go round.
AB - I've never felt the need to respond to an article before, but I had to comment on
the story about the NMC not increasing the L120 annual registration fee for
nurses (news, 5 April).
PMID- 28421919
TI - The power of music.
AB - At the end of the first year of my nursing degree I spent my clinical placement
in a hospice, where the majority of patients were admitted for palliative care.
PMID- 28421920
TI - Online bereavement support.
AB - How much difference can a virtual cup of tea make? A surprising amount, says
Elise Hoadley.
PMID- 28421921
TI - London trust enjoys boost in job applicants thanks to television documentary
series.
AB - A major London hospital trust that was the subject of a hit TV documentary series
has seen a surge in nurses and other staff applying to work there.
PMID- 28421922
TI - Student life - Taking a healthy approach to social networking.
AB - It can be difficult for nurses to maintain a good work-life balance, given the
commitments and pressures of their job.
PMID- 28421923
TI - Show you have the right attitude for the job.
AB - The 2013 Francis report into the Mid Staffs care scandal called for 'changes in
attitudes, culture, values and behaviour'. Since then, many NHS trusts have tried
to ensure their staff values align to those of the organisation and reflect the
NHS Constitution.
PMID- 28421925
TI - Get away from it all in the Shetlands.
AB - Fed up with the hustle and bustle of hospital life? A dream job has just come up
on the remote Scottish island of Fair Isle.
PMID- 28421926
TI - A Handbook for Student Nurses Benbow Wendy and Jordan Gill A Handbook for Student
Nurses 256pp L14.99 Lantern Publishing 9781908625373 1906052190 [Formula: see
text].
AB - Social media groups for nursing students are often inundated with excited new
students requesting pre-course reading recommendations. This book should be high
on the list for all new nursing students to have on their bookshelf.
PMID- 28421927
TI - Walking Forward, Looking Back Lantham Dinah Walking Forward, Looking Back 160pp
L8.99 Trobador Books 9781784620844 178462084X [Formula: see text].
AB - The author of Walking Forward, Looking Back is a retired district nurse and
midwife and this book is a heartwarming reflection on her life told as she
recalls past events while out walking her dog.
PMID- 28421928
TI - My Cortisol.
AB - My Cortisol is an app that helps to train parents and carers in how to give life
saving injections to children at risk of adrenal crisis.
PMID- 28421929
TI - The value of doing your best.
AB - Claire Matata is lead nurse for emergency and acute clinical research at
Northumbria Specialist Emergency Care Hospital. She completed her degree in adult
nursing at the University of Liverpool in 2010, and has worked in thoracic
surgery, community and prison nursing and as a specialist research nurse and
senior clinician in urgent care. In 2015, she spent three months in Sierra Leone
during the Ebola crisis.
PMID- 28421931
TI - Back to former Ebola zone.
AB - Pauline Cafferkey is planning to return to Sierra Leone for the first time since
falling seriously ill with the Ebola virus in 2014.
PMID- 28421930
TI - A difficult transition.
AB - More than 700,000 people in the UK are living with an eating disorder. They can
experience physical complications, poor quality of life, disrupted relationships,
emotional distress, social isolation and economic disadvantage. The risk of early
death is one of the highest among patients with psychiatric disorders.
PMID- 28421932
TI - Learning disability nurse numbers heading in the wrong direction.
AB - The UK's record on supporting people with learning disabilities is patchy to say
the least. For decades people were housed in inappropriate institutions where
abuse was rife, and attempts to improve their lives by delivering better services
in the community have come up short because they have not been afforded
sufficient priority.
PMID- 28421933
TI - RCN asks: are you prepared to strike for better pay?
AB - The RCN has opened an online poll on whether members would strike over pay. Some
270,000 RCN members are being asked for their views on NHS pay, two weeks after
governments in England, Scotland and Wales announced the latest below-inflation
pay increases.
PMID- 28421934
TI - Readers' panel - Should NHS staff be pressurised to give up their agency work?
AB - Our experts consider a hot topic of the day.
PMID- 28421935
TI - Health is your wealth - and your responsibility.
AB - What should I do? I mustn't nanny him. He is a grown man with a job. It is his
life, his health, his problem. But still.
PMID- 28421936
TI - British-led research uncovers new details on brain cancer.
AB - Scientists have found 13 new genetic errors associated with an increased risk of
developing glioma, the most common form of brain cancer.
PMID- 28421937
TI - Rules of attraction.
AB - Nottingham University Hospitals NHS Trust is the latest in a small, select band
of UK hospitals working to achieve Magnet hospital accreditation. Along with
Oxford University Hospitals and the Heart of England NHS Foundation Trust in
Birmingham, Nottingham is a key member of the new UK Magnet Alliance, which
brings together UK healthcare organisations interested in pursuing Magnet
recognition.
PMID- 28421938
TI - Agency nursing goes PAYE.
AB - Many agency nurses bill for their services through a limited or personal services
company. In the past, this has reduced the tax they need to pay, allowing some
profits to be taken as dividends. It has also allowed them to offset costs, such
as travel, against their profits.
PMID- 28421939
TI - The NMC wants to communicate in a way that works for you.
AB - Two years ago the Nursing and Midwifery Council (NMC) made a commitment, as part
of our five-year strategy, to be a leading, dynamic regulator. This means
protecting the public by being forward-looking and adapting our approach to
regulation to reflect the circumstances in which nurses and midwives work.
PMID- 28421940
TI - Not a level playing field.
AB - Your news story on the 'Nurse First' fast-track course is interesting (news
online, 31 March). Superficially, the two-year programme appears to be a good way
of recruiting talented and appropriately qualified graduates into a nursing
career.
PMID- 28421941
TI - Nurses need support, too.
AB - Like everyone, I feel for the family of Charlie Gard, the baby who the High Court
ruled last week should be allowed to die.
PMID- 28421944
TI - Awareness of heart failure unchanged in a decade.
AB - Campaigns on the risks of heart failure have failed to raise public awareness,
according to researchers.
PMID- 28421942
TI - The personal touch.
AB - The story on your Facebook page about nurses in Denmark breaking protocol to give
a dying man a glass of wine and a cigarette (11 April) reminded me of the time we
did the same thing for one of our patients on night duty.
PMID- 28421945
TI - Post-traumatic stress symptoms relieved by playing computer game.
AB - Playing the computer game Tetris can prevent post-traumatic stress symptoms,
researchers have found.
PMID- 28421947
TI - Budget cuts will hinder new nurse standards.
AB - The Council of Deans of Health has had more than a year of extensive engagement
with the Nursing and Midwifery Council's standards for future registered nurses.
PMID- 28421946
TI - 'It's a privilege to look after these children'.
AB - Moving from children's to adult services is a daunting time for any young person
and those who care for them, but for those with rare diseases it can be
particularly challenging.
PMID- 28421948
TI - Talk about fertility, even with children, says college.
AB - The RCN is encouraging nurses to talk about preserving fertility with young
people undergoing treatment that could make it difficult for them to conceive.
PMID- 28421949
TI - Vital signs.
AB - A snapshot of the state of health and social care.
PMID- 28421950
TI - Hospital visitors' experiences at the nurses' station.
AB - Aim To investigate participants' experiences of visiting hospitalised friends and
family members in adult acute medical or surgical wards in NHS hospitals in
England, to improve knowledge of hospital visiting practices and to inform future
policy-making and professional practice. Method A review of the contextual
influences and the literature identified that hospital visitors might experience
many of the characteristics of liminality, which is a state of being between two
social structures or ways of being. In 2013, a total of 17 semi-structured,
recorded and transcribed interviews were conducted with participants who had been
hospital visitors in the period 2011-2013. The transcribed interviews underwent a
thematic analysis. Liminality was then used as an analytic lens, and was central
to the theoretical framework that was constructed to further consider the
experiences of hospital visitors. Findings Participants experienced the
hospitalisation of their friend or family member and their subsequent role as
hospital visitors as a suspension of their everyday lives. Liminality was a
predominant and consistent theme of the interviews. Five main themes of
liminality were identified in relation to hospital visitors' experiences: total
obedience; loss of status; ambiguity and being betwixt and between; uncertainty;
and structure and communitas. The findings suggested that nurses consider the
area behind the nurses' station as 'back stage'; a place they can use for
downtime, socialising and computer work. In contrast, hospital visitors perceive
the nurses' station to be a continuation of the ward, where they expect
professional 'front stage behaviour' from staff. Conclusion When hospital
visitors, already discomfited in their liminal status, encounter nurses' 'back
stage behaviour' at the nurses' station, their feelings of marginalisation,
exclusion and mistrust increase. This may lead them to judge that the nurses lack
professionalism and care, which can lead them to make complaints. Increased
awareness of hospital visitors' perceptions might result in fewer complaints, and
enable more NHS resources to be directed at improving patient care.
PMID- 28421951
TI - Mindfulness.
AB - What was the nature of the CPD activity, practice-related feedback and/or event
and/or experience in your practice? The CPD article discussed mindfulness and
self-compassion, and how these concepts can improve nurses' well-being and their
ability to provide compassionate care.
PMID- 28421952
TI - Implementing spiritual care interventions.
AB - This article, the third and final in a series of three, discusses the
implementation of spiritual care interventions by nurses. It describes how nurses
can use clinical reasoning and the nursing process to implement appropriate
spiritual care for patients, and outlines the competencies necessary to identify
spiritual distress and meet the spiritual needs of patients. Spiritual care
interventions are discussed as part of a multidisciplinary team approach to the
provision of holistic care.
PMID- 28421953
TI - Multiple morbidities assessment.
AB - Essential facts Multimorbidity, when a person has two or more long-term health
conditions, is associated with a reduced quality of life, higher mortality,
polypharmacy and high treatment burden, higher rates of adverse drug events, and
much greater health service use.
PMID- 28421954
TI - Poor sleep linked to increased risk of heart attack and stroke.
AB - Insomnia is associated with an increased risk of heart attack and stroke,
according to a study in China. Researchers carried out a meta-analysis of 15
cohort studies to assess the association between insomnia symptoms and incidence
or death from cardiovascular disease and stroke.
PMID- 28421955
TI - Further evidence that taking statins can reduce risk of blood clots.
AB - More evidence has come to light that seems to suggest statins could significantly
reduce the occurrence of blood clots in certain parts of the body.
PMID- 28421956
TI - 'My midwife made childbirth a positive and enjoyable experience'.
AB - I was expecting my first baby. I was nervous and in slow labour. When I called
the maternity unit at Queen Elizabeth Hospital in Gateshead for reassurance over
the phone, midwife Anna Marley was on shift.
PMID- 28421957
TI - What the student saw: sharing placement experiences to improve practice.
AB - When nursing students go on clinical placement they see patient safety practice
in action - good and bad.
PMID- 28421958
TI - Acute limb compartment syndrome in the lower leg following trauma: assessment in
the intensive care unit.
AB - Acute limb compartment syndrome (ALCS) is a serious complication of traumatic
injury. Although ALCS can occur in any limb, it most commonly occurs following
injury to the lower leg, particularly in fractures of the tibia. Practitioners
should recognise and treat ALCS as early as possible to prevent the development
of further, potentially serious, complications. Most of the literature recommends
that patients at risk of ALCS should be carefully monitored, with a focus on pain
as the main symptom. However, patients in the intensive care unit (ICU) who are
unconscious or sedated may be unable to report pain or are unreliable in doing
so, therefore it is necessary to consider alternative assessments for ALCS. This
article provides an overview of the evidence and guidelines in relation to ALCS
in the lower leg and how to undertake an effective assessment for the condition
in patients in the ICU. This will enable practitioners to make evidence-based
clinical decisions to improve practice and patient safety.
PMID- 28421959
TI - Regulator penalises nurse who failed to start CPR.
AB - A nurse has been reprimanded by the Nursing and Midwifery Council (NMC) for
failing to begin cardiopulmonary resuscitation (CPR) on a care home resident that
he believed had already died.
PMID- 28421962
TI - Nurse's key role after Swedish attack.
AB - A nurse has spoken about being one of the first people on the scene of a terror
attack in the Swedish capital Stockholm this month.
PMID- 28421963
TI - Notice board.
AB - Courses, events, grants, and awards to progress your career.
PMID- 28421964
TI - Decline in degree places for learning disability nursing.
AB - The number of places on learning disability nursing undergraduate programmes have
either decreased or remained unchanged at 21 out of 24 universities in England in
the past two academic years, Nursing Standard can reveal.
PMID- 28421965
TI - Reducing premature mortality from non-communicable diseases.
AB - Cardiovascular disease and other non-communicable diseases, such as diabetes,
cancer and chronic respiratory disease, are a leading cause of premature death
and disability worldwide. This article emphasises the importance of prevention in
reducing death and disability from preventable non-communicable diseases,
especially for individuals with established risk factors for these diseases. It
reviews global initiatives to reduce morality rates from these diseases,
identifies opportunities for nurses and other healthcare professionals to discuss
risk factors with patients, and provides practical suggestions on how to provide
advice on healthy lifestyles and enable behaviour change.
PMID- 28421966
TI - Regulatory Forum Review*: Utility of in Vitro Secondary Pharmacology Data to
Assess Risk of Drug-induced Valvular Heart Disease in Humans: Regulatory
Considerations.
AB - Drug-induced valvular heart disease (VHD) is a serious side effect linked to long
term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B)
agonists. Safety assessment for off-target pharmacodynamic activity is a common
approach used to screen drugs for this undesired property. Such studies include
in vitro assays to determine whether the drug is a 5-HT2B agonist, a necessary
pharmacological property for development of VHD. Measures of in vitro binding
affinity (IC50, Ki) or cellular functional activity (EC50) are often compared to
maximum therapeutic free plasma drug levels ( fCmax) from which safety margins
(SMs) can be derived. However, there is no clear consensus on what constitutes an
appropriate SM under various therapeutic conditions of use. The strengths and
limitations of SM determinations and current risk assessment methodology are
reviewed and evaluated. It is concluded that the use of SMs based on Ki values,
or those relative to serotonin (5-HT), appears to be a better predictor than the
use of EC50 or EC50/human fCmax values for determining whether known 5-HT2B
agonists have resulted in VHD. It is hoped that such a discussion will improve
efforts to reduce this preventable serious drug-induced toxicity from occurring
and lead to more informed risk assessment strategies.
PMID- 28421967
TI - Lung Tumor Induction by 26-week Dermal Application of 1,2-Dichloroethane in CB6F1
Tg rasH2 Mice.
AB - Short-term alternatives to traditional 2-year carcinogenic studies in rodents are
being actively pursued. Recently, a 26-week short-term carcinogenicity study
using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the
evaluation of chemical carcinogenesis. However, an acceptable short-term
carcinogenic study model for dermally applied products is still lacking. To
investigate the suitability of using the rasH2 mouse to test carcinogenic
potential, 1,2-dichloroethane (1,2-DCE) was dermally applied to rasH2 mice: 1,2
DCE is a known carcinogen that causes lung bronchiolo-alveolar adenomas and
adenocarcinomas when administered topically, orally, or by inhalation exposure;
1,2-DCE at a dose level of 126 mg/mouse in 200 MUl acetone or acetone alone
(vehicle control) was applied to the dorsal skin of 10 mice of each sex 3 times a
week for 26 weeks. As a positive control, 10 mice of each sex received a single
intraperitoneal injection of 75 mg/kg of N-methyl- N-nitrosourea. Bronchiolo
alveolar adenomas and adenocarcinomas were significantly increased in 1,2-DCE
treated rasH2 mice of both sexes, and bronchiolo-alveolar hyperplasias were
significantly increased in female mice. Overall, almost all mice of each sex
developed adenomas and/or adenocarcinomas with 100% of female rasH2 mice
developing bronchiolo-alveolar adenocarcinomas.
PMID- 28421968
TI - Chronic Toxicology Studies of Basal Insulin Peglispro in Rats and Dogs: A Novel,
PEGylated Insulin Lispro Analog with a Prolonged Duration of Action.
AB - Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa
polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because
chronic parenteral administration of PEGylated proteins to animals has sometimes
resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and
choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc)
injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with
systemic toxicities or other changes, including vacuolation of tissue
macrophages, renal tubular cells, and ependymal cells. Rats and dogs received
daily sc injections of BIL (rats: 0.17, 0.45, or 1.15 mg/kg/d and dogs: 0.025,
0.10, or 0.20 mg/kg/d) and the reference compound, HUMULIN N(r) (neutral
protamine Hagedorn [NPH] human insulin; rats: 0.15 mg/kg/d and dogs: 0.02-0.03
mg/kg/d). Animals were evaluated for standard end points including mortality,
clinical signs, body weights, toxicokinetics, glucodynamics, clinical pathology,
and morphological pathology. Nonadverse injection site lipohypertrophy occurred
for all BIL and NPH doses but more frequently with BIL. No BIL-related
hyperplasia or neoplasia was observed. There was no vacuolation of tissue
macrophages, renal tubular cells, or ependymal cells attributable to PEG. These
studies demonstrate BIL is not associated with tissue vacuolation attributable to
PEG at 4- to 6-fold multiple of the median clinical exposure in patients with
diabetes.
PMID- 28421969
TI - Dystrophic Mineralization of Costal Cartilage in Hartley Guinea Pigs.
AB - Hartley guinea pigs are widely used animal models of disease, particularly in
studies of osteoarthritis. The purpose of this study was to investigate lesions
in the costal cartilage from 16 male, 5- to 6-month-old Hartley guinea pigs.
Routine histological sections from the costal cartilage and costochondral
junction (longitudinal and cross sections) and sternum (for evaluation of bone
marrow) were examined. All 16 (100%) animals had histological lesions involving
the costal cartilage that included matrix degeneration and mineralization,
reduced cellularity, and evidence of chondrocyte necrosis. Of the 16, 4 (25%) of
the lesions contained blood vessels and 3 (19%) contained central osseous
metaplasia. The cartilage lesions were accompanied by degeneration (sometimes
with regeneration and/or fibrosis) in adjacent skeletal muscle in 15 of the 16
(94%) animals. The lesions in the costal cartilage were interpreted as dystrophic
mineralization of unknown cause and appear to be incidental findings, although
they bear some resemblance to lesions occurring in Tietze's disease in humans.
The significance of the lesions in skeletal muscle is unclear. Histological
lesions of cartilage matrix degeneration and mineralization in these sites have
not, to our knowledge, been reported previously.
PMID- 28421970
TI - Management of Fractured Inferior Vena Cava Filters: Outcomes by Fragment
Location.
AB - Purpose To inform the management of fractured inferior vena cava filters on the
basis of results from a tertiary referral center specializing in complex filter
retrieval. Materials and Methods This study had institutional review board
approval and was HIPAA compliant. Retrospective analysis of all patients with
fractured filters and/or filter fragments evaluated for removal in a complex
filter removal program was performed. Removal was attempted when fragments were
intravascular or immediately extravascular by using primarily endobronchial
forceps for caval fragments and snares for cardiac and pulmonary fragments. Data
collected included success rate and complications of filter and fragment removal,
symptoms relating to the filter or fragment, techniques used for removal, and
follow-up of retained fragments. Results Sixty-five patients (12 men, 53 women)
of a total of 222 patients referred for complex retrieval had fractured filters.
Of these patients, two had undergone filter removal elsewhere and had retained
fragments. All 63 filters were removed successfully with forceps (n = 61), a cone
(n = 1), or a snare (n = 1). There were 116 separate filter fragments; removal
was attempted for 78 fragments. Removal was successful for 63 (81%) of 78
fragments and varied by location. All extravascular fragments except one were
retained. In all, 63 (54%) of 116 fragments were removed percutaneously,
rendering 34 (54%) of 63 patients fragment free. Five minor (7.7% [five of 65])
and four major (6.2% [four of 65]) complications occurred. Conclusion
Intravascular filter fragments can be removed safely with success rates that vary
according to location. Because extravascular fragments are not readily accessible
for removal, many patients are not rendered fragment free. (c) RSNA, 2017 Online
supplemental material is available for this article.
PMID- 28421971
TI - [Posttraumatic appendicitis].
AB - BACKGROUND: Posttraumatic appendicitis is an appendicitis that develops as a
consequence of abdominal trauma. Trauma is a relatively rare cause of
appendicitis which is nowadays rarely mentioned in surgical textbooks. CASE
DESCRIPTION: We describe the case of a 12-year-old girl who presented to the
emergency department six days after abdominal trauma caused by a fall from an
electrical bicycle, complaining of fever and abdominal pain. Her symptoms were
caused by a perforated appendicitis. Her recovery after appendectomy was
complicated by abscess formation and subsequent drainage, and the need for
parenteral nutrition CONCLUSION: Abdominal pain and fever several days after an
abdominal trauma may be a sign of posttraumatic appendicitis. The clinical signs
and diagnostic work-up do not differ significantly from that of appendicitis with
a different aetiology. Trauma is not a well-known cause of appendicitis, and this
can cause delay in diagnosis and treatment.
PMID- 28421972
TI - [A tumour mistaken for a scar].
AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare type of cutaneous
soft tissue sarcoma. The tumour metastasises rarely, but the percentage of
recurrences is high and the tumour can be locally very aggressive. CASE
DESCRIPTION: A 50-year-old man was referred to our clinic for a long existing
scar on his back, which had become painful in the last few weeks. In the hospital
we decided to take a biopsy. Based on the histopathological investigation, the
diagnosis DFSP was made. The patient was referred to a tertiary centre
specialising in rare skin malignancies. CONCLUSION: DFSP is clinically
heterogeneous with the consequence that several differential diagnoses can be
made. Histopathological examination is the gold standard diagnostic approach when
there is a possible suspicion of DFSP. Because of the aggressiveness and the high
recurrence rate it is very important to make a timely diagnosis, to allow
appropriate treatment - preferably radical excision - to take place.
PMID- 28421973
TI - [Bitten by an exotic venomous snake].
AB - BACKGROUND: Patients who have been bitten by an exotic venomous snake are at risk
of severe morbidity and a fatal outcome following an incorrect risk-assessment.
Treatment with an antivenom can be necessary and can turn out to be lifesaving.
In the Netherlands there are only a few cases of bites from exotic venomous
snakes each year. CASE DESCRIPTION: A 28-year-old man presented at the emergency
department (ED) after having been bitten by a monocled cobra (Naja kaouthia).
Here he developed severe neurotoxicity with respiratory insufficiency requiring
intubation and mechanical ventilation. The patient was successfully treated with
an antivenom. CONCLUSION: An exotic snakebite victim is always a medical
emergency. With early presentation at the ED, proper assessment, treatment and
the availability of antivenom from the National Serum Depot, this will not
necessarily cause insurmountable problems.
PMID- 28421974
TI - [Epigastric pain caused by a gastric wall abscess].
AB - BACKGROUND: Gastric wall abscesses are rare, but mortality rates from this type
of gastritis are high. A foreign body or mucosal damage is often the cause of the
abscess. Most patients have nonspecific symptoms, including general malaise and
abdominal pain, sometimes accompanied by fever and weight loss. CASE DESCRIPTION:
After various tests a 45-year-old man with epigastric pain was shown to have a
gastric wall abscess. After endoscopic drainage of the abscess, followed by
intravenous antibiotics, he made a complete recovery. CONCLUSION: Gastric wall
abscesses are rare, but should be included in the differential diagnosis in
patients with epigastric pain, because of their high mortality rate. Endoscopic
ultrasonography is the preferred diagnostic method. Endoscopic ultrasound-guided
drainage, with or without placement of a drain, followed by intravenous
antibiotics is the treatment of choice.
PMID- 28421975
TI - [Analysis of variation in the surgical treatment of distal radius fracture].
AB - OBJECTIVE: The optimum treatment of patients with distal radius fracture has not
been entirely clarified resulting in possible major variations between hospitals
in the number of patients undergoing surgical treatment. The objective of this
study was to examine the variation in surgical treatment rates of patients with
distal radius fractures across Dutch hospitals. DESIGN: Retrospective study.
METHOD: Aggregated data for all patients with a distal radius fracture were
obtained for 2012 and 2013 on the basis of reimbursement codes. The surgical rate
across hospitals was corrected for several variables using linear regression
analysis. RESULTS: We analysed a total of 95,754 reimbursements. The operative
rate ranged from 0% to 23%, with a mean of 9.6%. Hospital type, the percentage of
females, the percentage of patients over 65, the mean age, average socioeconomic
status, and the total number of patients treated explained only 2.6% of the
observed differences in operative rate between hospitals in 2012 and 11.6% in
2013. CONCLUSION: Our results suggest that non-scientific factors, such as
surgeon's age, background, and local culture, influence therapeutic decisions in
patients with distal radius fractures.
PMID- 28421976
TI - [Measles after MMR-vaccination].
AB - BACKGROUND: The Dutch national vaccination program provides vaccination for
mumps, measles and rubella (MMR vaccine) for all children. After vaccination with
live attenuated viruses, the virus replicates on a limited scale. Replication may
lead to mild symptoms occurring 5-14 days after MMR-vaccination, including fever,
conjunctivitis and rash. Symptoms are comparable to those of a wildtype measles
infection. CASE DESCRIPTION: A 14-month-old boy was admitted to the hospital with
an impressive rash 13 days after MMR-vaccination. Diagnostic tests were positive
for measles. This test result caused the mother to doubt further vaccination.
CONCLUSION: Within 14 days after MMR-vaccination, a child can present with
symptoms very similar to a wildtype measles virus infection. The low incidence of
wildtype measles infection strongly suggests that these symptoms will likely be a
reaction to vaccination. Elaborate diagnostic procedures may cause the parents a
lot of stress and therefore offering reassurance to parents may be more
appropriate.
PMID- 28421977
TI - [A woman with pink urine and a pink skin].
AB - A 48-year-old woman with fire-related inhalation injury had pink urine and a pink
skin. This was caused by hydroxocobalamin, which was used to treat cyanide
poisoning.
PMID- 28421978
TI - Improving Patient Safety Through Antibiotic Stewardship: The Veterans Health
Administration Leads the Way, Again.
PMID- 28421979
TI - Applying the Horizontal and Vertical Paradigm to Antimicrobial Stewardship.
PMID- 28421981
TI - Validation of MAX Aqueous Extraction on Veratox(r) for Total Aflatoxin ELISA Test
Kit.
AB - Neogen Corp. (Lansing, MI) has developed a common aqueous extraction method for
the detection of mycotoxins in the ELISA or lateral flow format. The Veratox(r)
for Total Aflatoxin ELISA extraction method uses a MAX 2 extraction packet and
water in replacement of traditionally used organic solvents. Veratox for Total
Aflatoxin has a detection range of 5-50 ppb neat or up to 300 ppb with dilution.
The kit development focused on superior cross-reactivity, ability to accurately
detect naturally contaminated samples, and utilization of an aqueous extraction
method. In two separate validation studies, the Veratox for Total Aflatoxin test
kit resulted in average yields of 91-114% in naturally contaminated mycotoxin
reference material corn. The cross-reactivity profiles for aflatoxins B1, B2, G1,
and G2 were 100, 113, 103, and 93%, respectively. This kit is approved by the
Grain Inspection, Packers, and Stockyards Administration.
PMID- 28421980
TI - Guidelines for the recognition and management of mixed depression.
AB - A significant minority of people presenting with a major depressive episode (MDE)
experience co-occurring subsyndromal hypo/manic symptoms. As this presentation
may have important prognostic and treatment implications, the DSM-5 codified a
new nosological entity, the "mixed features specifier," referring to individuals
meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or
to individuals with syndromal mania and subthreshold depressive symptoms. The
mixed features specifier adds to a growing list of monikers that have been put
forward to describe phenotypes characterized by the admixture of depressive and
hypomanic symptoms (e.g., mixed depression, depression with mixed features, or
depressive mixed states [DMX]). Current treatment guidelines, regulatory
approvals, as well the current evidentiary base provide insufficient decision
support to practitioners who provide care to individuals presenting with an MDE
with mixed features. In addition, all existing psychotropic agents evaluated in
mixed patients have largely been confined to patient populations meeting the DSM
IV definition of "mixed states" wherein the co-occurrence of threshold-level
mania and threshold-level MDE was required. Toward the aim of assisting
clinicians providing care to adults with MDE and mixed features, we have
assembled a panel of experts on mood disorders to develop these guidelines on the
recognition and treatment of mixed depression, based on the few studies that have
focused specifically on DMX as well as decades of cumulated clinical experience.
PMID- 28421982
TI - Simultaneous Determination of Volatile Organic Compounds in Commercial Alcoholic
Beverages by Gas Chromatography with Flame Ionization Detection.
AB - A simple and fast method was developed for the determination of volatile organic
compounds in alcoholic beverages. Eleven volatile organic compounds
(acetaldehyde, methanol, 2-propanol, tert-butanol, 1-propanol, ethyl acetate, 2
butanol, isobutanol, 1-butanol, 3-methyl-1butanol, and 2-methyl-1-butanol) in
alcoholic beverages were analyzed with a simple direct-injection method using GC
with flame ionization detection. These compounds should be monitored in the QC of
production processes because they are detrimental to human health. The method was
validated with four types of alcoholic beverages (beers, fruit wines, rice wines,
and spirits) to confirm the versatility of the method. Linearity showed r2 values
from 0.9986 to 0.9995, with LODs ranging from 0.010 to 1.000 mg/L. Precision and
accuracy showed acceptable results, proving the effectiveness of the method. The
developed method was applied to 40 commercial samples representing the four types
of alcoholic beverages, and principal component analysis was performed to
determine profiles of the volatile organic compounds, depending on the type of
alcoholic beverage.
PMID- 28421983
TI - Comparative Study Between Multivariate and Univariate Analysis of Two
Antidiabetic Combinations.
AB - New multivariate and univariate methods were developed for the analysis of two
novel gliptin combinations by manipulating the zero-order and ratio spectra of
empagliflozin and linagliptin in combination, with application on Glyxambi(r)
tablets, and of alogliptin and pioglitazone in combination, with application on
Oseni(r) tablets. Linearity ranges for chemometric approaches using principal
component regression and partial least-squares were found to be 2-10, 2.5-12.5, 5
15, and 5-25 MUg/mL for empagliflozin, linagliptin, alogliptin, and pioglitazone,
respectively, whereas the respective linearity ranges for the spectrophotometric
approaches were found to be 5-15, 2-12, 5-15, and 5-15 MUg/mL. The proposed
spectrophotometric methods included ratio subtraction coupled with extended ratio
subtraction, spectrum subtraction coupled with constant multiplication, and mean
centering. Acceptable LOD and LOQ values were obtained by all methods.
Statistical analysis showed no significant difference between multivariate and
univariate methods in comparison with the reference methods. The optimized
methods provide fast and economic determination of the recently approved
antidiabetic combinations without the complex instrumentation or time-consuming
mobile phase preparations that were used in the chromatographic techniques
reported in the literature.
PMID- 28421984
TI - Stability-Indicating UPLC Method for the Estimation of Nadifloxacin, Terbinafine
Hydrochloride, Mometasone Furoate, Methyl Paraben, and Propyl Paraben in Topical
Pharmaceutical Dosage Form.
AB - A novel and simple ultra-performance LC method was developed for the estimation
of nadifloxacin (NAD), terbinafine hydrochloride (TBH), mometasone furoate (MMF),
methyl paraben (MP), and propyl paraben (PP) in a topical pharmaceutical dosage
formulation. The analysis was carried out on a Waters Acquity UPLC ethylene
bridged hybrid C18 column (50 * 2.1 mm, 1.7 MUm) with a flow rate of 0.4 mL/min
in gradient mode at a wavelength of 255 nm. Elution of all components was
achieved within 9 min. The retention times of MP, NAD, PP, TBH, and MMF were
observed at 1.5, 2.6, 3.4, 6.0, and 6.9 min, respectively. The proposed method
was validated per current International Conference on Harmonization guidelines
for specificity, precision, linearity, accuracy, range, LOD, LOQ, robustness,
filter paper interference, and solution stability parameters. A complete method
study was performed to determine the stability-indicating nature of the developed
method.
PMID- 28421985
TI - Design of a Sensitive and Selective Electrochemical Aptasensor for the
Determination of the Complementary cDNA of miRNA-145 Based on the Intercalation
and Electrochemical Reduction of Doxorubicin.
AB - The aim of this research was the determination of a microRNA (miRNA) using a DNA
electrochemical aptasensor. In this biosensor, the complementary complementary
DNA (cDNA) of miRNA-145 (a sense RNA transcript) was the target strand and the
cDNA of miRNA-145 was the probe strand. Both cDNAs can be the product of the
reverse transcriptase-polymerase chain reaction of miRNA. The proposed
aptasensor's function was based on the hybridization of target strands with
probes immobilized on the surface of a working electrode and the subsequent
intercalation of doxorubicin (DOX) molecules functioning as the electroactive
indicators of any double strands that formed. Electrochemical transduction was
performed by measuring the cathodic current resulting from the electrochemical
reduction of the intercalated molecules at the electrode surface. In the
experiment, because many DOX molecules accumulated on each target strand on the
electrode surface, amplification was inherently easy, without a need for
enzymatic or complicated amplification strategies. The proposed aptasensor also
had the excellent ability to regenerate as a result of the melting of the DNA
duplex. Moreover, the use of DNA probe strands obviated the challenges of working
with an RNA probe, such as sensitivity to RNase enzyme. In addition to the linear
relationship between the electrochemical signal and the concentration of the
target strands that ranged from 2.0 to 80.0 nM with an LOD of 0.27 nM, the
proposed biosensor was clearly capable of distinguishing between complementary
(target strand) and noncomplementary sequences. The presented biosensor was
successfully applied for the quantification of DNA strands corresponding to miRNA
145 in human serum samples.
PMID- 28421986
TI - All-Solid-State, PVC Membrane, and Carbon Paste Ion-Selective Electrodes for
Determination of Donepezil Hydrochloride in Pharmaceutical Formulation.
AB - All-solid-state, polyvinyl chloride (PVC) membrane, and carbon paste
potentiometric ion-selective electrodes (ISEs) were proposed for the
determination of donepezil hydrochloride (DON) in the drug substance and a
pharmaceutical formulation. The potentiometric response toward DON was based on
the existence of donepezil-tetraphenyl borate (DON-TPB) in a PVC membrane or a
carbon paste in the presence of dioctylphthalate. In contrast, the solid-state
electrode was prepared by direct incorporation of DON-TPB into a commercial nail
varnish without external additives. The electrodes exhibited Nernstian slopes of
55.0, 57.0, and 53.0 mV/decade over the concentration ranges of 1 * 10-5 to 1 *
10-3, 1 * 10-4 to 10-2, and 1 * 10-4 to 5 * 10-3 for the solid-state, PVC
membrane, and carbon paste electrodes, respectively. The response of the
electrodes is independent of pH in the range of 2-<=8. The electrodes showed good
selectivity for DON with respect to a number of inorganic cations and amino
acids. The electrodes were used for the determination of DON in pure solution and
in pharmaceutical tablets with high accuracy (+/-2%) and precision (RSD <=2%).
The solid-state electrode is simple, economical, and rapid when compared to the
PVC membrane and carbon paste electrodes.
PMID- 28421987
TI - A New Dispersive Liquid-Liquid Microextraction Method for Preconcentration and
Determination of Aluminum, Iron, Copper, and Lead in Real Water Samples by HPLC.
AB - In this study, dispersive liquid-liquid microextraction coupled with HPLC with
variable-wavelength detection was applied for the simultaneous determination of
Al, Fe, Cu, and Pb in various water samples at trace levels. In the proposed
method, all the system parameters in both the extraction and
separation/determination steps, such as extraction and disperser solvent type and
their volumes, complexing reagent concentration, salt addition, extraction and
centrifugation times, and pH, were optimized to get not only high extraction
efficiency but also lower LODs for the analytes. Hematoxylin was used as a
complexing reagent, and carbon tetrachloride and methanol were chosen as the
extraction and disperser solvents, respectively. Metal complexes were separated
with a reversed-phase C18 column by isocratic elution, with methanol
tetrahydrofuran-water (20 + 12 + 68, v/v/v) as the mobile phase at a flow rate of
1.0 mL/min and detection at 575 nm. The accuracy of the method was checked by a
Standard Reference Material of water (SRM 1643e), and the recovery values for the
analytes were found in the range of 95.6-101.3%. Under the optimum conditions,
the developed method was applied to tap water, bottled mineral water, lake water,
and seawater for the accurate and sensitive determination of the analytes of
interest.
PMID- 28421988
TI - Composite Magnetic Nanoparticles (CuFe2O4) as a New Microsorbent for Extraction
of Rhodamine B from Water Samples.
AB - In this work, novel composite magnetic nanoparticles (CuFe2O4) were synthesized
based on sol-gel combustion in the laboratory. Next, a simple production method
was optimized for the preparation of the copper nanoferrites (CuFe2O4), which are
stable in water, magnetically active, and have a high specific area used as
sorbent material for organic dye extraction in water solution. CuFe2O4
nanopowders were characterized by field-emission scanning electron microscopy
(SEM), FTIR spectroscopy, and energy dispersive X-ray spectroscopy. The size
range of the nanoparticles obtained in such conditions was estimated by SEM
images to be 35-45 nm. The parameters influencing the extraction of CuFe2O4
nanoparticles, such as desorption solvent, amount of sorbent, desorption time,
sample pH, ionic strength, and extraction time, were investigated and optimized.
Under the optimum conditions, a linear calibration curve in the range of 0.75
5.00 MUg/L with R2 = 0.9996 was obtained. The LOQ (10Sb) and LOD (3Sb) of the
method were 0.75 and 0.25 MUg/L (n = 3), respectively. The RSD for a water sample
spiked with 1 MUg/L rhodamine B was 3% (n = 5). The method was applied for the
determination of rhodamine B in tap water, dishwashing foam, dishwashing liquid,
and shampoo samples. The relative recovery percentages for these samples were in
the range of 95-99%.
PMID- 28421989
TI - Application of an HPLC Method for Selective Determination of Phenazopyridine
Hydrochloride: Theoretical and Practical Investigations.
AB - HPLC method was developed for the selective determination of phenazopyridine
hydrochloride (PAP) in the presence of its computationally selected metabolite.
Density functional theory was applied as a computational model to study the
energy of PAP metabolites, and the results revealed that 2,3,6-triaminopyridine
(TAP) is the most stable metabolite. Good resolution and separation of PAP from
TAP was achieved using a reversed-phase BDS Hypersil C18 column with a mobile
phase consisting of acetonitrile-water (75 + 25, v/v) at flow rate of 1 mL/min
and with UV detection at 280 nm. The linear regression analysis data for the
calibration plot of PAP showed a good linear relationship over the concentration
range of 5-45 MUg/mL, with an LOD of 0.773 MUg/mL. Moreover, a theoretical
investigation of the relationship between the stationary phase and the studied
molecules was performed to confirm the experimental results. The proposed method
was successfully applied for the selective determination of PAP in pharmaceutical
formulation. In addition, the obtained results were statistically compared to a
reported method, with no significant differences found between the investigated
method and the reported one with respect to accuracy and precision.
PMID- 28421990
TI - Elevated levels of soluble CD40 ligand are associated with antiphospholipid
antibodies in patients with systemic lupus erythematosus.
AB - OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of
atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were
reported in SLE patients. However, the clinical implication of sCD40L in SLE
remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients
and 37 healthy controls and investigated its association with clinical
manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE
patients were significantly elevated compared with healthy controls (p=0.013) and
positively correlated with levels of soluble P-selectin (gamma=0.336, p<0.001).
SLE patients who experienced arterial thrombosis had a higher level of sCD40L
than those who did not (p=0.029). Plasma sCD40L levels were positively correlated
with the titers of anti-cardiolipin and anti-beta2 glycoprotein I antibodies
(gamma=0.338, p<0.001 and gamma=0.364, p<0.001, respectively). Its levels were
also significantly higher in patients with clinical antiphospholipid syndrome
(APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL)
positivity. Of those with arterial thrombosis, sCD40L levels were significantly
elevated in patients with positive aPL, compared to those with negative aPL
(p=0.011). Multiple regression analysis revealed that the presence of
hypertension and positive aPL were independently associated with the occurrence
of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L
was also an independent variable for arterial thrombosis; however, this
association disappeared when aPL, a strong variable, was included in the model
because of collinearity between aPL and sCD40L. CONCLUSIONS: Plasma sCD40L levels
were elevated in SLE patients who had positive aPL and experienced arterial
thrombosis, suggesting that enhanced release of sCD40L through platelet
activation presumably by aPL could contribute to the development of
atherothrombotic disease.
PMID- 28421991
TI - Patterns in use and costs of conventional and biologic disease-modifying anti
rheumatic drugs in Australia.
AB - OBJECTIVES: The aim of this study was to characterise the use and costs of
subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and
biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits
schemes. METHODS: Dispensing and expenditure data on conventional and biologic
DMARDs were extracted from Medicare Australia and temporal trends were analysed.
Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000
population per day (DDD/1,000 population/day). RESULTS: Conventional and biologic
DMARD use increased 74% over the study period (4.86 to 8.46 DDD/1,000
population/day; average annual increase 6.7%). Conventional DMARDs accounted for
the vast majority of total use and increased 55% (4.81 to 7.43 DDD/1,000
population/day), while biologic DMARD use increased 1,784% (0.055 to 1.030
DDD/1,000 population/day). The most frequently used conventional DMARD was
methotrexate (56% total conventional DMARD use) and use increased 95%.
Hydroxychloroquine and leflunomide use increased marginally while sulfasalazine
use declined 4.2%. Etanercept was the most commonly used biologic DMARD in 2004
and adalimumab in 2014. Conventional DMARD expenditure decreased 4.2% to AUD$33.3
million but biologic DMARD expenditure increased 2,089% to AUD$585.4 million.
CONCLUSIONS: The use of conventional and biologic DMARDs increased substantially
over a decade in Australia. Patterns of use of conventional DMARDs have changed,
and costs have decreased. In contrast a significant escalation in both the use
and cost of biologic DMARDs has occurred. Further research is required to address
cost-effectiveness, regulation and quality use of these medicines in clinical
practice.
PMID- 28421992
TI - Reply to comment on: Clinical efficacy of oral alendronate in ankylosing
spondylitis: a randomised placebo-controlled trial.
PMID- 28421994
TI - Reply to: Behcet's disease: an MHC-I-opathy?
PMID- 28421993
TI - Increased expression of interferon-lambda in minor salivary glands of patients
with primary Sjogren's syndrome and its synergic effect with interferon-alpha on
salivary gland epithelial cells.
AB - OBJECTIVES: To investigate the expressions of interferon (IFN)-lambdas and their
receptor, IL28RA, in minor salivary glands (MSG) of pSS patients and their
effects on the salivary gland cells. METHODS: The expressions of IFN-lambdas and
IL28RA were evaluated in MSG by immunohistochemistry in 15 patients with pSS and
in 5 patients with non-SS sicca. Poly(I:C)-induced IL-28A and IL-29 expressions
were determined in immortalized human salivary gland acinar (NS-SV-AC) and ductal
(NS-SV-DC) cell lines. We assessed the effect of IFN-lambdas on the expressions
of typical interferon-inducible genes, B-cell activating factor (BAFF) and
CXCL10, and the synergistic effect of IL-29 and type I or II IFN on their
expressions. The serum IL-29 levels were measured in 44 patients with pSS and 22
healthy controls. RESULTS: IFN-lambdas expression was significantly higher in MSG
from pSS than from non-SS sicca controls. Poly(I:C) treatment led to the
induction of IL-28A and IL-29 in the salivary gland cell lines. In the NS-SV-DC
cells, IFN-lambda significantly increased the levels of BAFF and CXCL10 in a time
and dose-dependent manner. Moreover, there was a synergistic effect between IL-29
and IFN-alpha in the induction of BAFF and CXCL10 expressions by prolonged STAT1
phosphorylation. However, the serum IL-29 levels were not significantly higher in
pSS patients than in healthy controls. CONCLUSIONS: Our results suggest the
possibility for IFN-lambda to play a role by participating local inflammation in
the salivary glands of pSS through direct and indirect regulations of the
expressions of BAFF and CXCL10 in salivary gland epithelium.
PMID- 28421995
TI - Endothelial dysfunction is independent of inflammation and altered CCR7 T cell
expression in patients with ankylosing spondylitis.
AB - OBJECTIVES: The accumulation of CCR7 (chemokine receptor 7) positive cells in the
vessel wall may be involved in endothelial dysfunction and subsequent accelerated
atherogenesis. CCR7 plays a crucial role in T cell and monocyte migration/homing
and in priming of naive T lymphocytes in non-lymphoid tissues in chronic
inflammatory diseases. Our objective was to investigate the endothelial function
and inflammation-driven expression of CCR7 on T lymphocytes in patients with
ankylosing spondylitis (AS). METHODS: We performed flow cytometry to assess the
distribution of peripheral blood T cell subpopulations in the context of serum
inflammatory markers (TNF-alpha, IL-6, sICAM-1) and asymmetric dimethylarginine
(ADMA) in 38 patients with AS with active disease, and in 20 healthy controls.
RESULTS: Patients with AS demonstrated higher ADMA (0.74+/-0.2 MUmol/l vs. 0.64+/
0.15 MUmol/l; p=0.03), as well as elevated inflammatory markers (TNFalpha, IL-6,
sICAM-1) and increased proportions of circulating CCR7-positive lymphocytes
largely attributable to elevated CD8+ naive T cells (47.1+/-17 vs. 34.3+/-13.1%;
p=0.005). However, ADMA did not correlate with either CCR7-positive lymphocytes
or inflammatory markers. CONCLUSIONS: We found an increased percentage of
peripheral CCR7 T cells accompanied by endothelial dysfunction in patients with
AS. The lack of direct associations between ADMA and inflammation may suggest the
presence of other pathogenic mechanisms contributing to accelerated atherogenesis
and increased cardiovascular risk in AS.
PMID- 28421996
TI - Obesity does not diminish the efficacy of IL-6 signalling blockade in mice with
collagen-induced arthritis.
AB - OBJECTIVES: Obese rheumatoid arthritis patients often have higher disease
activity and a poorer response to treatment than do non-obese patients. The
present study aims to clarify the influence of obesity on the action of IL-6 and
to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity.
METHODS: Mice were fed a high-fat diet for 5 weeks, and the influence of this
diet on macrophages and type II collagen-induced arthritis was investigated.
RESULTS: The mice fed the high-fat diet showed greater expression of macrophage
marker F4/80, not only in subcutaneous fat but also in knee synovium and the
calcaneal region, than did the mice fed a normal diet. Furthermore, macrophages
isolated from mice on the high-fat diet tended to show higher expression of
cyclooxygenase-2 following IL-6 stimulation than did macrophages from mice fed
the normal diet. Moreover, mice fed the normal or high-fat diet were immunised
with type II collagen, and were treated with anti-mouse IL-6 receptor antibody
(MR16-1). The anti-arthritis effect of MR16-1 was not reduced in mice fed the
high-fat diet compared to mice fed the normal diet (inhibition ratio: 87% vs.
62%). Furthermore, at the peak of arthritis, cyclooxygenase-2 expression in the
calcaneal region of mice fed the high-fat diet was higher than that in the mice
fed the normal diet. CONCLUSIONS: These results suggested that a high-fat diet
induces inflammatory changes in the synovium. We demonstrated that IL-6
signalling blockade by an anti-IL-6 receptor antibody can be effective in
treating arthritis, even with obesity.
PMID- 28421997
TI - Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific
markers in the salivary gland of Sjogren's syndrome patients.
AB - OBJECTIVES: Little is known about the molecular details regarding the
contribution of different cell types of the salivary gland to the altered gene
expression profile seen in Sjogren's syndrome (SS). METHODS: Using laser
microdissection, tissue samples enriched in acini, ducts and inflammatory foci in
subjects with and without SS were isolated for RNA-seq analysis. Gene expression
profiles were analysed and selected enriched genes were further examined using
real time PCR and by immunofluorescence. RESULTS: RNA-seq analysis of salivary
biopsies from subjects with and without SS revealed marked differences in gene
expression occurring in the ductal and infiltrating cells compared to acinar
cells. Up-regulated genes in the SS ductal cells included C4A complement and the
SLC26A9 ion channel. The inflammatory infiltrate showed the most dramatic
differences in gene expression and contained up-regulated genes associated with T
cells, natural killer, dendritic and basophils/mast cells. qPCR with total
salivary gland mRNA confirmed the differential mRNA expression of several genes
(MMP9, FOL1HB, CCL21, CCR7), thereby validating the approach. Additional
immunofluorescence studies demonstrated high expression and co-localisation of
CCL21 chemokine and CCR7 chemokine receptor within the SS infiltrates.
CONCLUSIONS: Major gene expression changes in the salivary gland of SS were
detected in the ductal and inflammatory cells and not in the acinar cells. Two
chemokines involved in immune cell trafficking to secondary lymphoid tissue, CCR7
and CCL21, showed markedly increased expression and may contribute to the
recruitment of diverse immune cells to the salivary glands, causing inflammation
and loss of secretory function.
PMID- 28421998
TI - Comment on: clinical efficacy of oral alendronate in ankylosing spondylitis: a
randomised placebo-controlled trial.
PMID- 28421999
TI - Use and withdrawal of immunosuppressors in primary Sjogren's syndrome.
AB - OBJECTIVES: To assess the use and causes of withdrawal of glucocorticoids and
immunosuppressors among patients with primary Sjogren's syndrome (pSS) in the
clinical setting. METHODS: We retrospectively reviewed the medical records of 155
pSS patients and registered demographics, glandular/extraglandular features,
serological data, cumulative ESSDAI and SSDDI. A single rheumatologist attributed
the indication and cause of withdrawal of glucocorticoids and immunosuppressors.
RESULTS: 92.2% of the patients were female, mean age 57.4+/-14.7 years and median
follow-up 11 years. One hundred and four (67%) patients received glucocorticoids
and/or immunosuppressors: 3.8% only glucocorticoids, 43.9% only immunosuppressors
and 56.5% their combination. The most used drugs were antimalarials (46.4%),
prednisone (36.7%), azathioprine (AZA) (23.8%) and methotrexate (MTX) (18%). At
the multivariate analysis, the presence of non-erosive arthritis OR 5.02 (95% CI
1.74-14.47, p=0.003) and the median cumulative ESSDAI score OR 1.10 (95% CI 1.03
1.17, p=0.002) were associated with the use of these drugs. The causes of
withdrawal were: 39% improvement, 35.2% patient's own decision, 18.1% toxicity
and 11% lack of efficacy. We found toxicity in 14.2% MTX users, 9.7% for AZA,
9.7% for antimalarials and 7.6% for cyclophosphamide. CONCLUSIONS: More than half
the patients received glucocorticoids and/or immunosuppressors and a not
negligible number decided on their own to suspend them, alerting physicians of
secondary adverse events and tolerability.
PMID- 28422000
TI - Fibromyalgia in 300 adult index patients with primary immunodeficiency.
AB - OBJECTIVES: We sought to determine the prevalence and clinical and laboratory
associations of fibromyalgia in adults with primary immunodeficiency
(immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable
immunodeficiency (CVID). METHODS: We performed a retrospective analysis of these
observations in 300 non-Hispanic white adult index patients with recurrent/severe
respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia;
chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC);
diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and
human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed
univariate comparisons, logistic multivariable regressions, and an analysis of
covariance. RESULTS: Mean age was 49 +/- 12 (standard deviation) y. There were
246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six
patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics
included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjogren's syndrome, 8.0%;
IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of
female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in
patients with fibromyalgia. Logistic regression on fibromyalgia revealed three
positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence
interval 1.2, 5.6]); Sjogren's syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC
(p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant
interactions of chronic fatigue, Sjogren's syndrome, and interstitial cystitis on
fibromyalgia. CONCLUSIONS: Fibromyalgia is common in non-Hispanic white adult
index patients with primary immunodeficiency, especially women. Chronic fatigue,
Sjogren's syndrome, and IC are significantly associated with fibromyalgia after
adjustment for other independent variables.
PMID- 28422001
TI - Microscopic polyangiitis and non-HBV polyarteritis nodosa with poor-prognosis
factors: 10-year results of the prospective CHUSPAN trial.
AB - OBJECTIVES: To analyse the 10-year outcomes of 64 patients with non-HBV
polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA) and Five-Factor
Score-defined poor-prognosis factors enrolled (1994-2000) in the prospective,
randomised, open-label CHUSPAN trial. METHODS: The 64 patients were randomised to
receive 12 (33: 23 MPA, 10 PAN) or 6 (31: 17 MPA, 14 PAN) cyclophosphamide (CYC)
pulses combined with glucocorticoids. Ten-year follow-up of these patients
included times to relapse(s), failure(s) and/or deaths calculated from treatment
onset. Data were censored after 120 months of follow-up. RESULTS: Eleven patients
were lost to-follow-up (mean+/-SD follow-up: 61.9+/-35.2 months), with no between
group difference. As previously reported, baseline clinical characteristics and
laboratory values were comparable for the 2 groups. After induction, 53/64 (83%)
entered remission, with comparable percentages for both groups. The regimen was
intensified for 11 initial non-responders: 4 achieved remission and 8 died before
doing so. During extended follow-up, 26 patients experienced >=1 relapse(s): 12
in the 12-pulse group and 14 in the 6-pulse group (p=0.47). At 10 years, overall
and disease-free survival rates were 57.4% and 29.9%, with no between-group
differences (p=0.185 and p=0.367, respectively). Factors associated with shorter
disease-free survival were age >=65 years and alveolar haemorrhage at diagnosis.
CONCLUSIONS: Although the 3-year CHUSPAN trial results indicated the superiority
of 12 vs. 6 CYC pulses, that early advantage progressively declined and became
non-significant by 10 years.
PMID- 28422002
TI - Treatment of psoriasis with ustekinumab improved skin tightening in systemic
sclerosis.
AB - Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by
fibrosis, inflammation and vasculopathy in the skin and internal organs.
Recently, several articles described that Th17 cells, IL-23 and IL-17 levels were
significantly elevated in the peripheral blood or fibrotic sites of SSc. We
report a case of SSc and psoriasis administered ustekinumab, IL-12/IL-23
inhibitor. In this case, the skin tightening was successfully improved and
ustekinumab was more effective, even though oral prednisolone (9-12 mg/day) had
some effect on skin tightening and arthralgia. We consider that inhibition of
Th17 cytokines may lead to therapeutic efficacy against SSc. Ustekinumab has the
potential for a treatment option of SSc.
PMID- 28422003
TI - Efficacy and safety of leflunomide as an adjuvant drug in refractory
dermatomyositis with primarily cutaneous activity.
AB - OBJECTIVES: To evaluate leflunomide as an adjuvant drug in refractory
dermatomyositis (DM) with primarily cutaneous activity. METHODS: A retrospective,
single-centre, cohort study including 18 adult patients with DM (classical or
clinically amyopathic DM) and cutaneous activity from 2001 to 2016 was conducted.
Patients were dependent on glucocorticoid and refractory to at least two full
dose immunosuppressants/immunomodulators or presented previous adverse events
with immunobiological drugs. One immunosuppressant was maintained and leflunomide
added to the treatment. Patients were followed for six consecutive months.
RESULTS: Leflunomide proved effective and safe in 12 (66.6%) out of the 18
patients. There was total control of cutaneous activity and prednisone was
tapered from 17.5 to 6.0 mg/day (p<0.001). In addition, two of these patients
that also had muscle involvement improved muscle strength after leflunomide
treatment. Side effects or inefficacy were observed in six patients. There were
no cases of serious infection or death. CONCLUSIONS: Leflunomide therapy appears
to be effective and safe as an adjuvant drug in refractory DM with primarily
cutaneous activity. Further studies are needed to confirm this data.
PMID- 28422004
TI - Performance of influenza case definitions for influenza community surveillance:
based on the French influenza surveillance network GROG, 2009-2014.
AB - International case definitions recommended by the Centers for Disease Control and
Prevention (CDC), the European Centre for Disease Prevention and Control (ECDC),
and the World Health Organization (WHO) are commonly used for influenza
surveillance. We evaluated clinical factors associated with the laboratory
confirmed diagnosis of influenza and the performance of these influenza case
definitions by using a complete dataset of 14,994 patients with acute respiratory
infection (ARI) from whom a specimen was collected between August 2009 and April
2014 by the Groupes Regionaux d'Observation de la Grippe (GROG), a French
national influenza surveillance network. Cough and fever >= 39 degrees C most
accurately predicted an influenza infection in all age groups. Several other
symptoms were associated with an increased risk of influenza (headache, weakness,
myalgia, coryza) or decreased risk (adenopathy, pharyngitis, shortness of breath,
otitis/otalgia, bronchitis/ bronchiolitis), but not throughout all age groups.
The WHO case definition for influenza-like illness (ILI) had the highest
specificity with 21.4%, while the ECDC ILI case definition had the highest
sensitivity with 96.1%. The diagnosis among children younger than 5 years remains
challenging. The study compared the performance of clinical influenza definitions
based on outpatient surveillance and will contribute to improving the
comparability of data shared at international level.
PMID- 28422005
TI - Blood donor screening for West Nile virus (WNV) revealed acute Usutu virus (USUV)
infection, Germany, September 2016.
AB - Between 1 June and 31 December 2016, 13,023 blood donations from the University
Hospital Aachen in Germany were routinely screened for West Nile virus (WNV) RNA
using the cobas TaqScreen WNV Test. On 28 September 2016, one blood donor was
tested positive. Subsequent analysis revealed an acute Usutu virus (USUV)
infection. During the ongoing USUV epizootics in Germany, blood transfusion
services, public health authorities and clinicians should be aware of increased
human USUV infections.
PMID- 28422006
TI - ECDC Round Table Report and ProMed-mail most useful international information
sources for the Netherlands Early Warning Committee.
AB - The Netherlands Early Warning Committee (NEWC) aims to identify infectious
diseases causing a potential threat to Dutch public health. Threats are assessed
and published as (information) alerts for public health experts. To identify
threats from abroad, the NEWC screens 10 sources reporting disease outbreaks each
week. To identify the sources essential for complete and timely reporting, we
retrospectively analysed 178 international alerts published between 31 January
2013 and 30 January 2014. In addition, we asked the four NEWC coordinators about
the required time to scan the information sources. We documented the date and
source in which the signal was detected. The ECDC Round Table (RT) Report and
ProMED-mail were the most complete and timely sources, reporting 140 of 178 (79%)
and 121 of 178 (68%) threats respectively. The combination of both sources
reported 169 (95%) of all threats in a timely manner. Adding any of the other
sources resulted in minor increases in the total threats found, but considerable
additional time investment per additional threat. Only three potential relevant
threats (2%) would have been missed by only using the ECDC RT Report and ProMed
mail. We concluded that using only the ECDC RT Report and ProMed-mail to identify
threats from abroad maintains a sensitive Early Warning System.
PMID- 28422007
TI - High risk of dengue type 2 outbreak in French Polynesia, 2017.
AB - In French Polynesia, the four serotypes of dengue virus (DENV-1 to -4) have
caused 14 epidemics since the mid-1940s. From the end of 2016, an increasing
number of Pacific Island Countries and Territories have reported DENV-2 outbreaks
and in February 2017, DENV-2 infection was detected in French Polynesia in three
travellers from Vanuatu. As DENV-2 has not been circulating in French Polynesia
since December 2000, there is high risk for an outbreak to occur.
PMID- 28422008
TI - Arabidopsis 14-3-3 epsilon members contribute to polarity of PIN auxin carrier
and auxin transport-related development.
AB - Eukaryotic 14-3-3 proteins have been implicated in the regulation of diverse
biological processes by phosphorylation-dependent protein-protein interactions.
The Arabidopsis genome encodes two groups of 14-3-3s, one of which - epsilon - is
thought to fulfill conserved cellular functions. Here, we assessed the in vivo
role of the ancestral 14-3-3 epsilon group members. Their simultaneous and
conditional repression by RNA interference and artificial microRNA in seedlings
led to altered distribution patterns of the phytohormone auxin and associated
auxin transport-related phenotypes, such as agravitropic growth. Moreover, 14-3-3
epsilon members were required for pronounced polar distribution of PIN-FORMED
auxin efflux carriers within the plasma membrane. Defects in defined post-Golgi
trafficking processes proved causal for this phenotype and might be due to lack
of direct 14-3-3 interactions with factors crucial for membrane trafficking.
Taken together, our data demonstrate a fundamental role for the ancient 14-3-3
epsilon group members in regulating PIN polarity and plant development.
PMID- 28422011
TI - The future of the NHS.
PMID- 28422009
TI - Axon tension regulates fasciculation/defasciculation through the control of axon
shaft zippering.
AB - While axon fasciculation plays a key role in the development of neural networks,
very little is known about its dynamics and the underlying biophysical
mechanisms. In a model system composed of neurons grown ex vivo from explants of
embryonic mouse olfactory epithelia, we observed that axons dynamically interact
with each other through their shafts, leading to zippering and unzippering
behavior that regulates their fasciculation. Taking advantage of this new
preparation suitable for studying such interactions, we carried out a detailed
biophysical analysis of zippering, occurring either spontaneously or induced by
micromanipulations and pharmacological treatments. We show that zippering arises
from the competition of axon-axon adhesion and mechanical tension in the axons,
and provide the first quantification of the force of axon-axon adhesion.
Furthermore, we introduce a biophysical model of the zippering dynamics, and we
quantitatively relate the individual zipper properties to global characteristics
of the developing axon network. Our study uncovers a new role of mechanical
tension in neural development: the regulation of axon fasciculation.
PMID- 28422010
TI - Synaptic input sequence discrimination on behavioral timescales mediated by
reaction-diffusion chemistry in dendrites.
AB - Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key
computational operations, including pattern recognition, event prediction, and
plasticity, involve neural discrimination of spatio-temporal sequences. Here, we
show that synaptically-driven reaction-diffusion pathways on dendrites can
perform sequence discrimination on behaviorally relevant time-scales. We used
abstract signaling models to show that selectivity arises when inputs at
successive locations are aligned with, and amplified by, propagating chemical
waves triggered by previous inputs. We incorporated biological detail using
sequential synaptic input onto spines in morphologically, electrically, and
chemically detailed pyramidal neuronal models based on rat data. Again, sequences
were recognized, and local channel modulation downstream of putative sequence
triggered signaling could elicit changes in neuronal firing. We predict that
dendritic sequence-recognition zones occupy 5 to 30 microns and recognize time
intervals of 0.2 to 5 s. We suggest that this mechanism provides highly parallel
and selective neural computation in a functionally important time range.
PMID- 28422012
TI - Syphilis: an ancient disease in a modern era.
PMID- 28422013
TI - Defunding the UNFPA: sign of the times.
PMID- 28422014
TI - Palliative care in humanitarian crises: always something to offer.
PMID- 28422015
TI - Offline: When The Lancet went to the Vatican.
PMID- 28422016
TI - Syria chemical attacks: preparing for the unconscionable.
PMID- 28422018
TI - Accounting for polio survivors in the post-polio world.
PMID- 28422017
TI - Research needed to prevent MERS coronavirus outbreaks.
PMID- 28422019
TI - Health systems resilience: meaningful construct or catchphrase?
PMID- 28422020
TI - Private water operators' contribution to realising the right to water.
PMID- 28422021
TI - Prevention of early-onset pre-eclampsia.
PMID- 28422022
TI - Maternal deaths and humanitarian crises.
PMID- 28422023
TI - Prevention of early-onset pre-eclampsia - Authors' reply.
PMID- 28422024
TI - Prolonged glucocorticoid treatment in acute respiratory distress syndrome.
PMID- 28422025
TI - Prolonged glucocorticoid treatment in acute respiratory distress syndrome -
Authors' reply.
PMID- 28422026
TI - Beyond ESPAC-4: better surgery and systemic therapy.
PMID- 28422027
TI - Stoop to conquer: preventing stroke and dementia together.
PMID- 28422028
TI - Department of Error.
PMID- 28422029
TI - Interpreting Treatment-Related Changes Using the Tinnitus Questionnaire in
Argstatter H, Grapp M, Plinkert PK, Bolay HV. Heidelberg Neuro-Music Therapy for
Chronic-tonal Tinnitus - Treatment Outline and Psychometric Evaluation. Int
Tinnitus J 2012;17(1):31-41.
PMID- 28422030
TI - Analysis of Hearing and Tinnitus in Workers Exposed to Occupational Noise.
AB - INTRODUCTION: Noise is one of the harmful agents to health that is present in the
various branches of economic activity. Hearing loss and tinnitus are among the
most frequently reported complaints by workers exposed to occupational noise.
OBJECTIVE: To analyze the hearing and tinnitus in normal-hearing workers exposed
to occupational noise. METHODS: This is a cross-sectional analytical trial in
metallurgical industries, in which we evaluated normal-hearing workers through
anamnesis, audiometry and otoacoustic emissions. RESULTS: It was observed high
prevalence of failure of otoacoustic emissions (40%) and tinnitus (66.6%). Both
in the amplitude and in the signal-to-noise ratio, the higher is the frequency of
the sound, the worse the results. Despite having audiometry within normal limits,
the results indicate that workers are suffering the effects of exposure and
reveals association between failure of otoacoustic emissions and tinnitus in this
population (X2 = 6,732). CONCLUSION: It is concluded that failures in DPOAE and
tinnitus are predictors of hearing damage in normal-hearing workers.
PMID- 28422031
TI - The Importance of Labyrinthine Examination in the Prognosis and Therapy for
Balance in Spinocerebellar Ataxia.
AB - INTRODUCTION: Spinocerebellar ataxias (SCAs) are a heterogeneous group of
neurodegenerative diseases that are characterized by the presence of progressive
cerebellar ataxia. OBJECTIVE: Identify vestibular disorders and demonstrate the
importance of labyrinthine examination in the prognosis and therapy for balance
in patients with SCAs. MATERIALS AND METHODS: The study had a retrospective cross
sectional design and evaluated 57 patients, mean age of 41.6 years and standard
deviation of 13 years. Patients underwent the following procedures: anamnesis,
ENT examination and vestibular exam using electronystagmography (ENG). RESULTS:
The most frequent complaints were gait imbalance (71.9%), dysarthria (49.1%),
dizziness (43.8%) and dysphagia (36.8%). 84.2% of the tests showed alterations.
The most common tests with alterations were the caloric test (78.9%), slow
saccades (61.4%) and the rotating chair test (49.1%). CONCLUSION: The clinical
history of the patient and oculomotor alterations in the labyrinthine examination
provide sufficient information for the proper use of virtual rehabilitation
protocols in the treatment of imbalance, making it the most effective therapy
method. It was evident that changes in ENG are related to the severity of the SCA
or the clinical stage of the disease. The labyrinthine examination proved to be
an important concomitant tool to clinical and genetic study.
PMID- 28422032
TI - A Tribute to Robert W. Entenmann (Bob)-12/10/16.
PMID- 28422033
TI - [Values and significances of the XX Century Medicine.]
PMID- 28422034
TI - Endocrine disruptors and prostate cancer.
AB - OBJECTIVES: Although prostate cancer is probably the most frequent cancer in men,
little is known about its etiology. Clear evidence exists about variations in the
incidence of prostate cancer between populations living in different countries.
These variations could be explained by differences in lifestyle and a possible
association with a set of substances that are able to intervene in the origin of
the disease. METHODS: The reason that lifestyle may be the cause of prostate
cancer is related to endocrine disruptors. These are a group of chemical
substances that can mimic or alter hormone signaling. These disruptors are able
to exert their effect at very low doses and act insidiously over the years, even
being able to pass their effect on from one generation to the next. Cholesterol
is an essential precursor in the synthesis of androgens, estrogens and other
substances that are active in prostate cancer. Cholesterol is a central
metabolite in lipid metabolism, the inflammatory response and other elements
involved in the formation and progression of cancer. High cholesterol
concentrations can give rise to the accumulation of androgens in tumor cells.
Additionally, endocrine disruptors have been identified as being responsible for
processes related with fertility, genital malformations and various
hormonedependent cancers. Disruptors already identified include
diethylstilbestrol, dichlorodiphenyltrichloroethane (DDT), polychlorinated
biphenyls and dioxins. RESULTS: Though no clear direct association has yet been
found in humans between most endocrine disruptors and prostate cancer, evidence
suggests that an inadequate diet and contact with certain toxic agents
predisposes to the disease. These disruptors are known to be especially relevant
at particular times, such as during pregnancy, neonatal stages and puberty.
CONCLUSIONS: The problem with these toxic agents is that their peculiarities and
way of acting over time make their study difficult. Nonetheless, research must be
encouraged given their importance.
PMID- 28422035
TI - [New therapeutic schedules of Sunitinib: Current evidence regarding the 2:1
scheme.]
AB - INTRODUCTION: In 2006, sunitinib approval by the FDA was a real revolution for
the treatment of metastatic renal cell carcinoma (mRCC). However, considerable
rates of dose reductions and therapeutic suppressions with the standard regimen
(4:2) have forced the search for new schedule proposals in order to optimize the
balance between side effects and oncologic efficacy. Among these new proposals,
the 2:1 scheme is the one that has generated more expectations. OBJECTIVE: The
objective of this paper is to make a review and critical discussion of current
evidence about the new schedules of treatment with sunitinib. METHODS:
Unstructured review of the literature on the various therapeutic regimens with
sunitinib, making a comparison in terms of progression-free survival (PFS),
overall survival (OS) and toxicity. RESULTS: We summarize the data from all
relevant studies published to date comparing the standard 4:2 schedule versus the
new 2:1. Most patients treated with 2:1 scheme are grouped in three retrospective
observational studies and mostly correspond to patients who were initially
treated with a 4:2 scheme and then moved to 2:1. A phase II randomized clinical
trial comparing 4:2 and 2:1 schemes from the beginning has also been conducted.
None of these studies found significant differences between the two regimens in
terms of PFS or OS. Regarding the toxicity profile, the 2:1 scheme has proved to
be more advantageous than the 4:2. CONCLUSIONS: Despite the still limited amount
of data, current evidence supports the use of a 2:1 schedule, as it provides
patients substantial advantages because of its better tolerability profile,
without a loss in oncological efficacy. Currently, the 2:1 scheme is an
appropriate alternative therapeutic strategy, especially in patients with poor
tolerance to the standard 4:2 regimen.
PMID- 28422036
TI - Physicochemical factors of the urine of children with hypercalciuria.
AB - OBJECTIVE: Hypercalciuria is a common lithogenic risk factor. The aim of this
study was, first, to study the characteristics of urine biochemical factors of
children with hypercalciuria (HC) and compare them with those of children without
hypercalciuria. Second, to analyze the differences between children with HC and
lithiasis (HCL) and children with HC and no lithiasis (HCNL). METHODS: The sample
was composed by 111 cases with HC, divided into 2 groups: HCNL group, consisting
of 93 cases with no personal history of kidney stones, and HCL group, 18 cases
with personal history of kidney stones. As a cohort control group, 113 healthy
children were used. Creatinine, urea, sodium, potassium, chlorine, uric acid,
calcium, phosphorus, magnesium and osmolality: blood and 24-hour urine following
parameters were determined. Oxalate and citrate were determined in urine.
RESULTS: The mean values of natriuresis, uricosuria, phosphaturia, magnesuria,
citraturia, calcium oxalate and calcium phosphate saturation were higher in HCNL
than in control group. The HCL group had phosphaturia, calcium oxalate and
calcium phosphate saturations more elevated compared with the control group.
There were no significant differences in urinary excretion of various parameters
when the groups HCL and HCNL were compared. CONCLUSIONS: Our results show that
children with hypercalciuria without lithiasis associated show an increase in
natriuresis, phosphaturia, uricosuria, magnesuria and citraturia. We found no
differences between these urinary abnormalities when compared hypercalciuric
children without lithiasis with those with hypercalciuria and urolithiasis.
PMID- 28422037
TI - Ureteral meatotomy as an option in the management of primary obstructive
megaureter in neonates and infants.
AB - : Differentiating between the cases of megaureter that require surgery and the
ones in whom treatment can be delayed is challenging. A large number of surgical
techniques for the treatment of POM been proposed aiming mainly to reduce renal
damage by relieving the affected ureter. Resection of the affected ureteral
segment followed by vesicoureteral reimplantation either with or without
reduction ureteroplasty is the classic treatment, however posing a high rate of
complications when performed in patients aged less than one year. Endoscopic
techniques have also been described to avoid external diversion. Recently,
refluxing ureteral reimplantation has been proposed as a temporary treatment for
patients with POM. OBJECTIVE: To describe the ureteral meatotomy technique as an
alternative to the refluxing ureteral reimplantation for POM in patients aged
less than one year. METHOD: Retrospective study of patients with POM undergoing
ureteral meatotomy, aiming to temporarily relieve the ureter. The procedure
consists of a 1.5 cm-long cut made with scissors on the upper edge of the
ureteral ostium at the 12 o'clock position, until the dilated portion of the
ureter was found and abundant urine drainage was observed. The edges of the
incision were sutured, joining together the ureteral mucosa and the bladder
mucosa. RESULT: From 2011 to 2015, three patients with POM underwent ureteral
meatotomy, with four renal units treated altogether. None of the patients
presented complications and, as a sign of obstruction relief, all showed reduced
dilatation at the ultrasound. No patient had complications. CONCLUSIONS: Ureteral
meatotomy is a safe and effective technique in the initial treatment of POM in
patients aged less than one year.
PMID- 28422038
TI - Treatment of urachal disorders: The open and laparoscopic surgery approach.
AB - INTRODUCTION: The present study analyzes cases of urachal abnormalities treated
with laparoscopic approach in our hospital. CASE DESCRIPTION: A retrospective
descriptive study of urachal disorders with laparoscopic surgery approach
performed at our hospital in the period 1999-2015. Patients' clinical data are
presented (radiological findings, surgical data, pathology findings,
complications and a follow-up of each patient). RESULTS: 7 Adults presented
complicated urachal disorders treated laparoscopically. The average age was 43.1
years old (DE +/-11). The mean surgical time of laparoscopic management was 154.2
minutes (range 120-240). Mean hospital stay was 4.9 days (DE +/-1.1). There were
no early or late postoperative complications. CONCLUSION: Laparoscopic removal of
urachal remnants is a safe and reproducible technique.
PMID- 28422039
TI - [Urinary tract lymphoepithelial carcinoma. Report of two cases and bibliographic
review.]
AB - OBJECTIVE: We report two cases of patients diagnosed with lymphoepithelioma-like
carcinomas of the urinary tract. We review the literature of this rare entity.
The objective is to clarify the clinical and therapeutic characteristics.
METHODS: We present a retrospective review of medical records of two patients
diagnosed with lymphoepithelioma-like carcinomas, one in the renal pelvis and the
other in the bladder. We review the epidemiology, diagnosis and therapeutic
alternatives. RESULTS: Case 1: A 74-year-old women with past medical history of
left radical nephrectomy and retroperitoneal lymphadenectomy six years before for
renal pelvis carcinoma type pure lymphoepithelioma-like, stage pT4R0pN1cM0. She
received adjuvant chemotherapy with Cisplatin and Gemcitabine. Five years later,
she presented tumor recurrence in the left ureteral meatus, this lesion was
resected. The pathology reported a high-grade urothelial carcinoma with marked
lymphoid component, stage pT1. At follow-up, one year after the last recurrence,
the patient was asymptomatic. In tomography control, no local or distant
recurrences were objectified. Case 2: A 82-year-old men with diagnosis of
muscleinvasive bladder cancer. The tumor caused right obstructive uropathy
without extracapsular, regional or remote extension. We performed a radical
cystoprostatectomy with bilateral pelvic lymphadenectomy and urinary diversion
type cutaneous transureterostomy. The pathology reported a urothelial bladder
carcinoma type mixed lymphoepithelioma-like, stage pT4aR1pN2cM0. At six months
follow-up, the patient had liver and spleen lesions and retroperitoneal
adenopathic nodes, all suggestive of metastases. He is currently receiving
symptomatic treatment of their disease. CONCLUSIONS: We emphasize the clinical
importance involved in the diagnosis of this entity. The diagnosis influence the
aggressiveness of treatment and disease-specific survival. Therefore, concomitant
transitional cell carcinoma defines the prognosis. The role of
immunohistochemical staining is fundamental, allowing us to confirm the presence
of the epithelial component.
PMID- 28422040
TI - Carcinoma of the penis.
PMID- 28422041
TI - Image diagnosis of emphysematous cystitis.
PMID- 28422042
TI - Synchronous penoscrotal implantation of penile prosthesis and artificial urinary
sphincter after radical prostatectomy.
AB - OBJECTIVES: To evaluate the results of synchronous dual implantation of penile
(PP) and artificial urinary sphincter prosthesis (AUSP) in patients with severe
erectile dysfunction (ED) and urinary incontinence (UI) after radical
prostatectomy (RP). METHODS: Between January 2006 and March 2015, patients who
underwent synchronous dual implantation of PP for severe post-RP ED and AUSP for
moderate to severe post-RP UI in our clinic were screened retrospectively. The
erectile function and the continence status were evaluated by the questionnaires
of IIEF-5 and ICIQ-SF. Results for the preoperative period and for the 1st
postoperative year were revealed from patient charts. Long term results were
evaluated by telephone interviews. Comorbidities, infection rates and
complications were noted. RESULTS: A total of 14 patients underwent synchronous
dual implantation; out of which, 11 had a long enough follow up period for a
sufficient long term evaluation. 3/11 had MPP and 8/11 had two-piece IPP
implantation together with an AUSP. All of the implantations were carried out
through an upper transverse scrotal incision. Mean follow up time was 61.3 +/- 20
months. In 1 patient who had received adjuvant radiotherapy, both of the devices
were removed due to infection and cuff erosion. Mean daily usage of pads
diminished from 4 to 1 while ICIQ-SF score decreased from 19 to 2 and IIEF-5
score increased from 3 to 23. CONCLUSION: Synchronous implantation of PP and AUSP
is a safe and effective treatment option for patients with severe ED and moderate
to severe UI after RP.
PMID- 28422043
TI - Real-world efficacy and safety of ritonavir-boosted paritaprevir, ombitasvir,
dasabuvir +/- ribavirin for hepatitis C genotype 1 - final results of the REV1TAL
study.
AB - BACKGROUND: Limited data exist on the outcomes of ritonavir-boosted paritaprevir
with ombitasvir and dasabuvir (PrOD) +/- ribavirin in a real-world setting. The
aim of this study was to compare the efficacy and safety of PrOD-based therapy in
hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre
treatment factors predictive of sustained viral response (SVR) and serious
adverse events (SAEs) on treatment. METHODS: 451 patients with hepatitis C
genotype 1 treated in 20 centres across Australia were included. Baseline
demographic, clinical and laboratory information, on-treatment biochemical,
virological and haematological indices and details on serious adverse events were
collected locally. RESULTS: Cirrhosis was present in 340 patients (75.4%).
Overall SVR was 95.1% with no differences in SVR between the cirrhosis and non
cirrhosis groups (94.7% versus 96.4%). SVR in subgenotypes 1a and 1b was 93.1%
and 99.2%, respectively. On multivariate analysis, baseline bilirubin level and
early treatment cessation predicted SVR. SAEs occurred in 10.9% of patients
including hepatic decompensation (2.7%) and hepatocellular carcinoma (1.8%). On
multivariate analysis of factors predictive of SAEs in the overall group, Child
Turcotte-Pugh (CTP) B was the only significant factor, while in those with
cirrhosis, baseline albumin and creatinine levels were significant. CONCLUSIONS:
In this large real-world cohort of HCV genotype 1 subjects, treatment with PrOD
was highly effective and similar to clinical trials. Important determinants of
reduced SVR include early cessation of therapy and baseline bilirubin
concentration. SAEs were not infrequent with CTP B patients being at greatest
risk.
PMID- 28422044
TI - Design of flexible PANI-coated CuO-TiO2-SiO2 heterostructure nanofibers with high
ammonia sensing response values.
AB - We report a room-temperature ammonia sensor with extra high response values and
ideal flexibility, including polyaniline (PANI)-coated titanium dioxide-silicon
dioxide (TiO2-SiO2) or copper oxide-titanium dioxide-silicon dioxide (CuO-TiO2
SiO2) composite nanofibers. Such flexible inorganic TiO2-SiO2 and CuO-TiO2-SiO2
composite nanofibers were prepared by electrospinning, followed by calcination.
Then, in situ polymerization of aniline monomers was carried out with inorganic
TiO2-SiO2 and CuO-TiO2-SiO2 composite nanofibers as templates. Gas sensing tests
at room temperature indicated that the obtained CuO-TiO2-SiO2/PANI composite
nanofibers had much higher response values to ammonia gas (ca. 45.67-100 ppm)
than most of those reported before as well as the prepared TiO2-SiO2/PANI
composite nanofibers here. These excellent sensing properties may be due to the P
N, P-P heterojunctions and a structure similar to field-effect transistors formed
on the interfaces between PANI, TiO2, and CuO, which is p-type, n-type, and p
type semiconductor, respectively. In addition, the prepared free-standing CuO
TiO2-SiO2/PANI composite nanofiber membrane was easy to handle and possessed
ideal flexibility, which is promising for potential applications in wearable
sensors in the future.
PMID- 28422045
TI - Sequential reduction of the silicon single-electron transistor structure to
atomic scale.
AB - Here we present an original CMOS compatible fabrication method of a single
electron transistor structure with extremely small islands, formed by solitary
phosphorus dopants in the silicon nanobridge. Its key feature is the controllable
size reduction of the nanobridge in sequential cycles of low energy isotropic
reactive ion etching that results in a decreased number of active charge centers
(dopants) in the nanobridge from hundreds to a single one. Electron transport
through the individual phosphorous dopants in the silicon lattice was studied.
The final transistor structure demonstrates a Coulomb blockade voltage of ~30 mV
and nanobridge size estimated as [Formula: see text]. Analysis of current
stability diagrams shows that electron transport in samples after the final
etching stage had a single-electron nature and was carried through three
phosphorus atoms. The fabrication method of the demonstrated structure allows it
to be modified further by various impurities in additional etching and
implantation cycles.
PMID- 28422046
TI - Nanowelding and patterning of silver nanowires via mask-free atmospheric cold
plasma-jet scanning.
AB - Silver nanowire (AgNW) thin film is a promising candidate to replace traditional
indium tin oxide in optoelectronics applications. To date however, the widespread
application of AgNW thin film is limited by the weak point contacts between
individual AgNWs and the lack of facile patterning techniques. Here, we
demonstrate a novel and facile method to not only nanoweld AgNW junctions but
also pattern AgNW thin films via mask-free cold plasma-jet scanning in ambient
conditions. After the plasma-jet nanowelding treatment, the morphology of AgNWs
change substantially and the junctions are welded together. The nanowelded AgNWs
based thin film shows enhanced electrical and mechanical properties. On the other
hand, after the plasma-jet patterning treatment, the AgNWs are etched and
transformed into separated large particles. Different kinds of patterns are
produced via this patterning technique. At last, a simple light emitting diode
circuit is fabricated to demonstrate the suitability of the nanowelded and
patterned AgNW electrodes for flexible electronic devices.
PMID- 28422047
TI - Template for the neural control of directed stepping generalized to all legs of
MantisBot.
AB - We previously developed a neural controller for one leg of our six-legged robot,
MantisBot, that could direct locomotion toward a goal by modulating leg-local
reflexes with simple descending commands from a head sensor. In this work, we
successfully apply an automated method to tune the control network for all three
pairs of legs of our hexapod robot MantisBot in only 90 s with a desktop
computer. Each foot's motion changes appropriately as the body's intended
direction of travel changes. In addition, several results from studies of walking
insects are captured by this model. This paper both demonstrates the broad
applicability of this control method for robots, and suggests neural mechanisms
underlying observations from walking insects.
PMID- 28422048
TI - SAK-HV Decreases the Self-Ubiquitination of MEKK1 to Promote Macrophage
Proliferation via MAPK/ERK and JNK Pathways.
AB - SAK-HV is an anti-atherosclerosis recombinant fusion protein developed by our
lab. Our study determined that SAK-HV promoted macrophage proliferation, of which
the mechanism was explored by both RAW264.7 cells and primary macrophages. Mass
spectrometric analysis and co-immunoprecipitation were combined to screen the SAK
HV-interacting proteins in RAW264.7 cells. Confocal microscopy was adopted to
detect the localization of SAK-HV in cells. The results indicated that SAK-HV
triggered macrophage proliferation via the mitogen-activated protein kinase
(MAPK)/extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases
(JNK) pathways by its SAK-mutant functional domain. We screened out Uba1 as the
SAK-HV-interacting protein in the RAW264.7 cells and discovered their co
localization in the cytoplasm and nucleus. Inhibiting Uba1 significantly
decreased the SAK-HV-induced macrophage proliferation. Thus, we postulated an
attractive model of ubiquitination, in which the interactions between Uba1 and
specific E2 enzymes are blocked by its interaction with SAK-HV. Based on this
model, we detected the decreased self-ubiquitination of MEKK1 after SAK-HV
treatment and concluded that SAK-HV inhibits the self-ubiquitination of MEKK1 via
its SAK-mutant functional domain to activate MAPK/ERK and JNK pathways, promoting
macrophage proliferation. This conclusion highly supported our hypothesized model
of ubiquitination at the level of Uba1, which may represent a novel paradigm to
promote macrophage proliferation by using the E1 enzyme (Uba1) as a switch.
PMID- 28422049
TI - Regulation of Anthocyanin Biosynthesis in Purple Leaves of Zijuan Tea (Camellia
sinensis var. kitamura).
AB - Plant anthocyanin biosynthesis is well understood, but the regulatory mechanism
in purple foliage tea remains unclear. Using isobaric tag for relative and
absolute quantification (iTRAQ), 815 differential proteins were identified in the
leaves of Zijuan tea, among which 20 were associated with the regulation of
anthocyanin metabolism. We found that the abundances of anthocyanin synthesis
related enzymes such as chalcone synthase, chalcone isomerase, dihydroflavonol 4
reductase and anthocyanin synthetase, as well as anthocyanin accumulation-related
UDP-glucosyl transferase and ATP-binding cassette (ABC) transporters in the
purple leaves were all significantly higher than those in the green leaves. The
abundances of the transcription factors bHLH and HY5, regulating anthocyanin
biosynthesis at transcriptional level were also obviously higher in purple leaves
than those in green leaves. In addition, bifunctional 3-dehydroquinate
dehydratase and chorismate mutase in purple leaves were distinctly higher in
abundance compared to green leaves, which provided sufficient phenylalanine
substrate for anthocyanin synthesis. Furthermore, lignin synthesis was found to
be reduced due to the lower abundances of cinnamoyl-CoA reductase 1, peroxidase
15 and laccase-6, which resulted in increase of intermediates flow into
anthocyanin synthesis pathway. The physiological data were consistent with
proteomic results. These four aspects of biosynthetic regulation contribute to
anthocyanin accumulation in purple leaves of Zijuan tea.
PMID- 28422050
TI - K-mer Content, Correlation, and Position Analysis of Genome DNA Sequences for the
Identification of Function and Evolutionary Features.
AB - In genome analysis, k-mer-based comparison methods have become standard tools.
However, even though they are able to deliver reliable results, other algorithms
seem to work better in some cases. To improve k-mer-based DNA sequence analysis
and comparison, we successfully checked whether adding positional resolution is
beneficial for finding and/or comparing interesting organizational structures. A
simple but efficient algorithm for extracting and saving local k-mer spectra
(frequency distribution of k-mers) was developed and used. The results were
analyzed by including positional information based on visualizations as genomic
maps and by applying basic vector correlation methods. This analysis was
concentrated on small word lengths (1 <= k <= 4) on relatively small viral
genomes of Papillomaviridae and Herpesviridae, while also checking its usability
for larger sequences, namely human chromosome 2 and the homologous chromosomes
(2A, 2B) of a chimpanzee. Using this alignment-free analysis, several regions
with specific characteristics in Papillomaviridae and Herpesviridae formerly
identified by independent, mostly alignment-based methods, were confirmed.
Correlations between the k-mer content and several genes in these genomes have
been found, showing similarities between classified and unclassified viruses,
which may be potentially useful for further taxonomic research. Furthermore,
unknown k-mer correlations in the genomes of Human Herpesviruses (HHVs), which
are probably of major biological function, are found and described. Using the
chromosomes of a chimpanzee and human that are currently known, identities
between the species on every analyzed chromosome were reproduced. This
demonstrates the feasibility of our approach for large data sets of complex
genomes. Based on these results, we suggest k-mer analysis with positional
resolution as a method for closing a gap between the effectiveness of alignment
based methods (like NCBI BLAST) and the high pace of standard k-mer analysis.
PMID- 28422053
TI - Erratum: Wong, L.P., et al. The Self-Regulation Model of Illness: Comparison
between Zika and Dengue and Its Application to Predict Mosquito Prevention
Behaviours in Malaysia, a Dengue-Endemic Country Int. J. Environ. Res. Public
Health 2016, 13, 1210.
AB - n/a.
PMID- 28422052
TI - Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in
Streptozotocin-Induced Diabetic Mice.
AB - High incidence rate of Alzheimer's disease (AD) is observed in patients with type
2 diabetes. Aggregated beta-amyloid (Abeta) and hyperphosphorylated tau are the
hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as
well as in diabetic patients. Folates mediate the transfer of one carbon unit,
required in various biochemical reactions. The effect of folate on tau
phosphorylation in diabetic models still remains unknown. In this study, we
investigated the effect and mechanism of folic acid on hyperphosphorylation of
tau in streptozotocin (STZ)-induced diabetic mice. Diabetic mice induced by STZ,
at the age of 10 weeks, were administered with three levels of folic acid: folic
acid-deficient diet, diet with normal folic acid content, and 120 MUg/kg folic
acid diet for 8 weeks. Levels of serum folate and blood glucose were monitored.
Tau phosphorylation, protein phosphatase 2A (PP2A) methylation, and Glycogen
synthase kinase 3beta (GSK-3beta) phosphorylation were detected using Western
blot. The S-adenosyl methionine:S-adenosyl homocysteine ratio (SAM:SAH) in brain
tissues was also determined. DNA methyltransferase (DNMT) mRNA expression levels
were detected using real-time PCR. Folic acid reduced tau hyperphosphorylation at
Ser396 in the brain of diabetes mellitus (DM) mice. In addition, PP2A methylation
and DNMT1 mRNA expression were significantly increased in DM mice post folic acid
treatment. GSK-3beta phosphorylation was not regulated by folic acid
administration. Folic acid can reduce tau phosphorylation by regulating PP2A
methylation in diabetic mice. These results support that folic acid can serve as
a multitarget neuronal therapeutic agent for treating diabetes-associated
cognitive dysfunction.
PMID- 28422054
TI - Growth Inhibition of Sulfate-Reducing Bacteria in Produced Water from the
Petroleum Industry Using Essential Oils.
AB - Strategies for the control of sulfate-reducing bacteria (SRB) in the oil industry
involve the use of high concentrations of biocides, but these may induce
bacterial resistance and/or be harmful to public health and the environment.
Essential oils (EO) produced by plants inhibit the growth of different
microorganisms and are a possible alternative for controlling SRB. We aimed to
characterize the bacterial community of produced water obtained from a Brazilian
petroleum facility using molecular methods, as well as to evaluate the
antimicrobial activity of EO from different plants and their major components
against Desulfovibrio alaskensis NCIMB 13491 and against SRB growth directly in
the produced water. Denaturing gradient gel electrophoresis revealed the presence
of the genera Pelobacter and Marinobacterium, Geotoga petraea, and the SRB
Desulfoplanes formicivorans in our produced water samples. Sequencing of dsrA
insert-containing clones confirmed the presence of sequences related to D.
formicivorans. EO obtained from Citrus aurantifolia, Lippia alba LA44 and
Cymbopogon citratus, as well as citral, linalool, eugenol and geraniol, greatly
inhibited (minimum inhibitory concentration (MIC) = 78 ug/mL) the growth of D.
alaskensis in a liquid medium. The same MIC was obtained directly in the produced
water with EO from L. alba LA44 (containing 82% citral) and with pure citral.
These findings may help to control detrimental bacteria in the oil industry.
PMID- 28422051
TI - Annexins as Overlooked Regulators of Membrane Trafficking in Plant Cells.
AB - Annexins are an evolutionary conserved superfamily of proteins able to bind
membrane phospholipids in a calcium-dependent manner. Their physiological roles
are still being intensively examined and it seems that, despite their general
structural similarity, individual proteins are specialized toward specific
functions. However, due to their general ability to coordinate membranes in a
calcium-sensitive fashion they are thought to participate in membrane flow. In
this review, we present a summary of the current understanding of cellular
transport in plant cells and consider the possible roles of annexins in different
stages of vesicular transport.
PMID- 28422055
TI - c-MYC-Making Liver Sick: Role of c-MYC in Hepatic Cell Function, Homeostasis and
Disease.
AB - Over 35 years ago, c-MYC, a highly pleiotropic transcription factor that
regulates hepatic cell function, was identified. In recent years, a considerable
increment in the number of publications has significantly shifted the way that
the c-MYC function is perceived. Overexpression of c-MYC alters a wide range of
roles including cell proliferation, growth, metabolism, DNA replication, cell
cycle progression, cell adhesion and differentiation. The purpose of this review
is to broaden the understanding of the general functions of c-MYC, to focus on c
MYC-driven pathogenesis in the liver, explain its mode of action under basal
conditions and during disease, and discuss efforts to target c-MYC as a plausible
therapy for liver disease.
PMID- 28422056
TI - Adiponectin and Intelectin-1: Important Adipokine Players in Obesity-Related
Colorectal Carcinogenesis.
AB - Overweight is believed to be associated with colorectal cancer risk. Adipose
tissue is loose connective tissue composed of adipocytes. It is now recognized as
a major endocrine organ, secreting humoral factors collectively called
adipokines. Aberrant hormonal systems consisting of modulated adipokines and
their receptors are thought to play a role in colorectal carcinogenesis and
cancer progression in obese conditions. However, it is still unclear whether and
how each adipokine relates to colorectal carcinogenesis. Notably, a couple of
molecules that were initially proposed to be obesity-related adipokines were
disqualified by subsequent studies. The adipokines, adiponectin, and intelectin-1
(also known as omentin-1), whose levels are decreased in obesity, act as tumor
suppressor factors in various cancers. Numerous studies have demonstrated a link
between the insufficient expression and function of adiponectin and its receptor,
T-cadherin, in colorectal carcinogenesis. Moreover, our recent study indicated
that loss of TMEM207, which is critical for the proper processing of intelectin-1
in the colon mucosa, leads to insufficient intelectin-1 production, thus
participating in colorectal carcinogenesis. Here, we discuss the recent
understanding of the role of adipokines in colorectal carcinogenesis and
subsequently describe the potent tumor suppressor roles of intelectin-1 and
TMEM207 in colorectal cancer.
PMID- 28422057
TI - Antifungal and Anti-Biofilm Activities of Acetone Lichen Extracts against Candida
albicans.
AB - Candida albicans is a commensal coloniser of the human gastrointestinal tract and
an opportunistic pathogen, especially thanks to its capacity to form biofilms.
This lifestyle is frequently involved in infections and increases the yeast
resistance to antimicrobials and immune defenses. In this context, 38 lichen
acetone extracts have been prepared and evaluated for their activity against C.
albicans planktonic and sessile cells. Minimum inhibitory concentrations of
extracts (MICs) were determined using the broth microdilution method. Anti
biofilm activity was evaluated using tetrazolium salt (XTT) assay as the ability
to inhibit the maturation phase (anti-maturation) or to eradicate a preformed 24
h old biofilm (anti-biofilm). While none of the extracts were active against
planktonic cells, biofilm maturation was limited by 11 of the tested extracts.
Seven extracts displayed both anti-maturation and anti-biofilm activities (half
maximal inhibitory concentrations IC50_mat and IC50_biof <= 100 ug/mL); Evernia
prunastri and Ramalina fastigiata were the most promising lichens (IC50_mat < 4
ug/mL and IC50_biof < 10 ug/mL). Chemical profiles of the active extracts
performed by thin layer chromatography (TLC) and high performance liquid
chromatography (HPLC) have been analyzed. Depsides, which were present in large
amounts in the most active extracts, could be involved in anti-biofilm
activities. This work confirmed that lichens represent a reservoir of compounds
with anti-biofilm potential.
PMID- 28422058
TI - Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases.
AB - Melatonin is a hormone synthesised and secreted by the pineal gland and other
organs. Its secretion, controlled by an endogenous circadian cycle, has been
proven to exert immunological, anti-oxidant, and anti-inflammatory effects that
can be beneficial in the treatment of certain dental diseases. This article is
aimed at carrying out a review of the literature published about the use of
melatonin in the dental field and summarising its potential effects. In this
review article, an extensive search in different databases of scientific journals
was performed with the objective of summarising all of the information published
on melatonin use in dental diseases, focussing on periodontal diseases and dental
implantology. Melatonin released in a natural way into the saliva, or added as an
external treatment, may have important implications for dental disorders, such as
periodontal disease, as well as in the osseointegration of dental implants, due
to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated
to have beneficial effects on dental pathologies, although further research is
needed to understand the exact mechanisms of this molecule.
PMID- 28422059
TI - Mismatch between Probiotic Benefits in Trials versus Food Products.
AB - Probiotic food products contain a variety of different bacterial strains and may
offer different health effects. The objective was to document the prevalence and
dosage of probiotic strains in the Canadian food supply and to review the
literature investigating these strains in order to understand what health
benefits these products may offer. The Food Label Information Program was used to
identify probiotic-containing products in the food supply. PubMed, Web of
Science, and Embase were searched for randomized controlled trials that tested
the health effects of these strains in humans. There were six probiotic
strains/strain combinations identified in the food supply. Thirty-one studies
investigated these strains and found that they are associated with decreased
diarrhea and constipation, improved digestive symptoms, glycemic control,
antioxidant status, blood lipids, oral health, and infant breastfeeding outcomes,
as well as enhanced immunity and support for Helicobacter pylori eradication.
There were a limited number of studies investigating these strains. Many studies
were funded by the food industry and tested dosages that were up to twenty-five
times the dosage found in most food products. Probiotic food products could have
health benefits not currently reported on their labels. However, many dosages are
too low to provide the benefits demonstrated in clinical trials. Further research
is needed to enable more effective use of these functional foods.
PMID- 28422061
TI - The Effect of Particles on Electrolytically Polymerized Thin Natural MCF Rubber
for Soft Sensors Installed in Artificial Skin.
AB - The aim of this study is to investigate the effect of particles as filler in soft
rubber sensors installed in artificial skin. We examine sensors made of natural
rubber (NR-latex) that include magnetic particles of Ni and Fe3O4 using magnetic
compound fluid (MCF). The 1-mm thickness of the electrolytically polymerized MCF
rubber makes production of comparatively thin rubber sensors feasible. We first
investigate the effect of magnetic particles Ni and Fe3O4 on the curing of MCF
rubber. Next, in order to adjust the electric properties of the MCF rubber, we
adopt Al2O3 dielectric particles. We investigate the effect of Al2O3 particles on
changes in electric current, voltage and temperature of electrolytically
polymerized MCF rubber liquid, and on the electric properties under the
application of normal and shear forces. By adjusting the ratio of Ni, Fe3O4,
Al2O3 and water in MCF rubber with Al2O3, it is possible to change the electric
properties.
PMID- 28422062
TI - Cross Layer Design for Optimizing Transmission Reliability, Energy Efficiency,
and Lifetime in Body Sensor Networks.
AB - High transmission reliability, energy efficiency, and long lifetime are pivotal
issues for wireless body area networks (WBANs. However, these performance metrics
are not independent of each other, making it hard to obtain overall improvements
through optimizing one single aspect. Therefore, a Cross Layer Design Optimal
(CLDO) scheme is proposed to simultaneously optimize transmission reliability,
energy efficiency, and lifetime of WBANs from several layers. Firstly, due to the
fact that the transmission power of nodes directly influences the reliability of
links, the optimized transmission power of different nodes is deduced, which is
able to maximize energy efficiency in theory under the premise that requirements
on delay and jitter are fulfilled. Secondly, a relay decision algorithm is
proposed to choose optimized relay nodes. Using this algorithm, nodes will choose
relay nodes that ensure a balance of network energy consumption, provided that
all nodes transmit with optimized transmission power and the same packet size.
Thirdly, the energy consumption of nodes is still unbalanced even with optimized
transmission power because of their different locations in the topology of the
network. In addition, packet size also has an impact on final performance
metrics. Therefore, a synthesized cross layer method for optimization is
proposed. With this method, the transmission power of nodes with more residual
energy will be enhanced while suitable packet size is determined for different
links in the network, leading to further improvements in the WBAN system. Both
our comprehensive theoretical analysis and experimental results indicate that the
performance of our proposed scheme is better than reported in previous studies.
Relative to the relay selection and power control game (RSPCG) scheme, the CLDO
scheme can enhance transmission reliability by more than 44.6% and prolong the
lifetime by as much as 33.2%.
PMID- 28422063
TI - Tellurite and Tellurate Reduction by the Aerobic Anoxygenic Phototroph
Erythromonas ursincola, Strain KR99 Is Carried out by a Novel Membrane Associated
Enzyme.
AB - Erythromonas ursincola, strain KR99 isolated from a freshwater thermal spring of
Kamchatka Island in Russia, resists and reduces very high levels of toxic
tellurite under aerobic conditions. Reduction is carried out by a constitutively
expressed membrane associated enzyme, which was purified and characterized. The
tellurite reductase has a molecular weight of 117 kDa, and is comprised of two
subunits (62 and 55 kDa) in a 1:1 ratio. Optimal activity occurs at pH 7.0 and 28
degrees C. Tellurite reduction has a Vmax of 5.15 umol/min/mg protein and a Km
of 3.36 mM. The enzyme can also reduce tellurate with a Vmax and Km of 1.08
umol/min/mg protein and 1.44 mM, respectively. This is the first purified
membrane associated Te oxyanion reductase.
PMID- 28422064
TI - Dried Plums, Prunes and Bone Health: A Comprehensive Review.
AB - The 2015-2020 Dietary Guidelines for Americans advocate for increasing fruit
intake and replacing energy-dense foods with those that are nutrient-dense.
Nutrition across the lifespan is pivotal for the healthy development and
maintenance of bone. The National Osteoporosis Foundation estimates that over
half of Americans age 50+ have either osteoporosis or low bone mass. Dried plums,
also commonly referred to as prunes, have a unique nutrient and dietary bioactive
profile and are suggested to exert beneficial effects on bone. To further
elucidate and summarize the potential mechanisms and effects of dried plums on
bone health, a comprehensive review of the scientific literature was conducted.
The PubMed database was searched through 24 January 2017 for all cell, animal,
population and clinical studies that examined the effects of dried plums and/or
extracts of the former on markers of bone health. Twenty-four studies were
included in the review and summarized in table form. The beneficial effects of
dried plums on bone health may be in part due to the variety of phenolics present
in the fruit. Animal and cell studies suggest that dried plums and/or their
extracts enhance bone formation and inhibit bone resorption through their actions
on cell signaling pathways that influence osteoblast and osteoclast
differentiation. These studies are consistent with clinical studies that show
that dried plums may exert beneficial effects on bone mineral density (BMD). Long
term prospective cohort studies using fractures and BMD as primary endpoints are
needed to confirm the effects of smaller clinical, animal and mechanistic
studies. Clinical and prospective cohort studies in men are also needed, since
they represent roughly 29% of fractures, and likewise, diverse race and ethnic
groups. No adverse effects were noted among any of the studies included in this
comprehensive review. While the data are not completely consistent, this review
suggests that postmenopausal women may safely consume dried plums as part of
their fruit intake recommendations given their potential to have protective
effects on bone loss.
PMID- 28422065
TI - Detection of (1,3)-beta-d-Glucan for the Diagnosis of Invasive Fungal Infection
in Liver Transplant Recipients.
AB - Invasive fungal infections (IFI) are complications after liver transplantation
involving high morbidity and mortality. (1,3)-beta-d-glucan (BG) is a biomarker
for IFI, but its utility remains uncertain. This study was designed to evaluate
the impact of BG following their diagnosis. Between January 2013 and May 2016,
271 liver transplants were performed in our institution. Serum samples were
tested for BG (Fungitell(r), Associates Cape Code Inc., Falmouth, MA, USA) at
least weekly between liver transplantation and the discharge of patients.
Nineteen patients (7%) were diagnosed with IFI, including 13 cases of invasive
candidiasis (IC), eight cases of invasive pulmonary aspergillosis, and one case
of septic arthritis due to Scedosporium apiospernum. Using a single BG sample for
the primary analysis of IFI, 95% (21/22) of the subjects had positive BG (>80
pg/mL) at the time of IFI diagnosis. The area under the ROC curves to predict IFI
was 0.78 (95% CI: 0.73-0.83). The sensitivity, specificity, positive predictive
value (PPV) and negative predictive value (NPV) of BG for IFI were 75% (95% CI:
65-83), 65% (62-68), 17% (13-21), and 96% (94-97), respectively. Based on their
high NPV, the BG test appears to constitute a good biomarker to rule out a
diagnosis of IFI.
PMID- 28422066
TI - Diabetogenic Effects of Ochratoxin A in Female Rats.
AB - In this study, the diabetogenic effects of long term Ochratoxin A (OTA)
administration in rats were investigated, and its role in the etiology of
diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these
purposes. The rats were divided into three different study and control groups
according to the duration of the OTA administration. The rats received 45 MUg OTA
daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups
were also used for the same time periods. Blood and pancreatic tissue samples
were collected during the necropsy at the end of the 6, 9 and 24 weeks. The
plasma values of insulin, glucagon and glucose were determined for the study and
control groups. Pancreatic lesions were evaluated via histopathological
examination and insulin and glucagon expression in these lesions was subsequently
determined using immunohistochemical methods. Statistically significant decreases
in insulin levels were observed, in contrast to increases in blood glucagon and
glucose levels. Histopathological examinations revealed slight to moderate
degeneration in Langerhans islet cells in all OTA-treated groups.
Immunohistochemistry of pancreatic tissue revealed decreased insulin and
increased glucagon expression. This study demonstrated that OTA may cause
pancreatic damage in the Langerhans islet and predispose rats to DM.
PMID- 28422060
TI - Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite
Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.
AB - Ghrelin is a hormone predominantly produced in and secreted from the stomach.
Ghrelin is involved in many physiological processes including feeding, the stress
response, and in modulating learning, memory and motivational processes. Ghrelin
does this by binding to its receptor, the growth hormone secretagogue receptor
(GHSR), a receptor found in relatively high concentrations in hypothalamic and
mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can
be explained by the effects of this hormone on regions of the brain that have a
more permeable blood brain barrier (BBB), ghrelin produced within the periphery
demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are
expressed. Therefore, one of the most pressing unanswered questions plaguing
ghrelin research is how GHSRs, distributed in brain regions protected by the BBB,
are activated despite ghrelin's predominant peripheral production and poor
ability to transverse the BBB. This manuscript will describe how peripheral
ghrelin activates central GHSRs to encourage feeding, and how central ghrelin
synthesis and ghrelin independent activation of GHSRs may also contribute to the
modulation of feeding behaviours.
PMID- 28422067
TI - Synthesis, Characterization, Antimicrobial and Antiproliferative Activity
Evaluation of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) Complexes with Isoniazid
Derived Compound.
AB - Hydrazone complexes of Cu(II), Co(II), Zn(II), Ni(II) and Pt(II) with N
isonicotinoyl-N'-(3-metoxy-2 hydroxybenzaldehyde)-hydrazone (HL) were synthesized
and characterized by different physico-chemical techniques including elemental
and thermal analysis, magnetic susceptibility measurements, molar electric
conductivity, as well as IR (infrared), 1H-NMR and 13C-NMR (hydrogen and carbon
nuclear magnetic resonance, UV-Vis (ultraviolet-visible), FAB (fast atom
bombardment), EPR (electron paramagnetic resonance), and mass spectroscopies. The
crystal structure of ligand was determined by single crystal X-ray diffraction
studies. Spectral data showed that hydrazone behaves as an ONO tridentate ligand
through the azomethine nitrogen, phenolate and keto oxygen atoms. For the
copper(II) complexes, metal-ligand bonding parameters were evaluated from the EPR
spectra. These parameters indicate the presence of in-plane pi bonding. In
addition, the f values of complexes 1-4 indicate small distortion from planarity.
The effect of these complexes on proliferation of human breast cancer (MCF-7 and
SKBR-3), human melanoma (A375), lung adenocarcinoma cells (NCI-H1573) and their
antibacterial activity against Escherichia coli, Klebsiella pneumoniae,
Staphylococcus aureus and Candida albicans strains were studied and compared with
those of free ligand. The ligand and complexes 1-3 showed significant
antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus
and Candida albicans in comparison to the control drugs. The complexes 2-4 could
be potential antitumor agents, leading to a significant improvement of the
cytotoxic activity when compared with HL.
PMID- 28422068
TI - A Low Cost Bluetooth Low Energy Transceiver for Wireless Sensor Network
Applications with a Front-end Receiver-Matching Network-Reusing Power Amplifier
Load Inductor.
AB - In this work, a low cost Bluetooth Low Energy (BLE) transceiver for wireless
sensor network (WSN) applications, with a receiver (RX)-matching network-reusing
power amplifier (PA) load inductor, is presented. In order to decrease the die
area, only two inductors were used in this work. Besides the one used in the
voltage control oscillator (VCO), the PA load inductor was reused as the RX
impedance matching component in the front-end. Proper controls have been applied
to achieve high transmitter (TX) input impedance when the transceiver is in the
receiving mode, and vice versa. This allows the TRX-switch/matching network
integration without significant performance degradation. The RX adopted a low-IF
structure and integrated a single-ended low noise amplifier (LNA), a current
bleeding mixer, a 4th complex filter and a delta-sigma continuous time (CT)
analog-to-digital converter (ADC). The TX employed a two-point PLL-based
architecture with a non-linear PA. The RX achieved a sensitivity of -93 dBm and
consumes 9.7 mW, while the TX achieved a 2.97% error vector magnitude (EVM) with
9.4 mW at 0 dBm output power. This design was fabricated in a 0.11 MUm
complementary metal oxide semiconductor (CMOS) technology and the front-end
circuit only occupies 0.24 mm2. The measurement results verify the effectiveness
and applicability of the proposed BLE transceiver for WSN applications.
PMID- 28422069
TI - Protein Stability and Unfolding Following Glycine Radical Formation.
AB - Glycine (Gly) residues are particularly susceptible to hydrogen abstraction;
which results in the formation of the capto-dative stabilized Calpha-centered Gly
radical (GLR) on the protein backbone. We examined the effect of GLR formation on
the structure of the Trp cage; tryptophan zipper; and the villin headpiece; three
fast-folding and stable miniproteins; using all-atom (OPLS-AA) molecular dynamics
simulations. Radicalization changes the conformation of the GLR residue and
affects both neighboring residues but did not affect the stability of the Trp
zipper. The stability of helices away from the radical center in villin were also
affected by radicalization; and GLR in place of Gly15 caused the Trp cage to
unfold within 1 us. These results provide new evidence on the destabilizing
effects of protein oxidation by reactive oxygen species.
PMID- 28422070
TI - One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon
Plasma Jet.
AB - Multiple evidence in animal models and in humans suggest a beneficial role of
cold physical plasma in wound treatment. Yet, risk assessment studies are
important to further foster therapeutic advancement and acceptance of cold plasma
in clinics. Accordingly, we investigated the longterm side effects of repetitive
plasma treatment over 14 consecutive days in a rodent full-thickness ear wound
model. Subsequently, animals were housed for 350 days and sacrificed thereafter.
In blood, systemic changes of the proinflammatory cytokines interleukin 1beta and
tumor necrosis factor alpha were absent. Similarly, tumor marker levels of alpha
fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the
expression levels of several cytokines and tumor markers in liver, lung, and skin
were found to be similar in the control and treatment group as well. Likewise,
histological and immunohistochemical analysis failed to detect abnormal
morphological changes and the presence of tumor markers such as carcinoembryonic
antigen, alpha-fetoprotein, or the neighbor of Punc11. Absence of neoplastic
lesions was confirmed by non-invasive imaging methods such as anatomical magnetic
resonance imaging and positron emission tomography-computed tomography. Our
results suggest that the beneficial effects of cold plasma in wound healing come
without apparent side effects including tumor formation or chronic inflammation.
PMID- 28422071
TI - Comparative Analysis of the Complete Chloroplast Genome of Four Endangered
Herbals of Notopterygium.
AB - Notopterygium H. de Boissieu (Apiaceae) is an endangered perennial herb endemic
to China. A good knowledge of phylogenetic evolution and population genomics is
conducive to the establishment of effective management and conservation
strategies of the genus Notopterygium. In this study, the complete chloroplast
(cp) genomes of four Notopterygium species (N. incisum C. C. Ting ex H. T. Chang,
N. oviforme R. H. Shan, N. franchetii H. de Boissieu and N. forrestii H. Wolff)
were assembled and characterized using next-generation sequencing. We
investigated the gene organization, order, size and repeat sequences of the cp
genome and constructed the phylogenetic relationships of Notopterygium species
based on the chloroplast DNA and nuclear internal transcribed spacer (ITS)
sequences. Comparative analysis of plastid genome showed that the cp DNA are the
standard double-stranded molecule, ranging from 157,462 bp (N. oviforme) to
159,607 bp (N. forrestii) in length. The circular DNA each contained a large
single-copy (LSC) region, a small single-copy (SSC) region, and a pair of
inverted repeats (IRs). The cp DNA of four species contained 85 protein-coding
genes, 37 transfer RNA (tRNA) genes and 8 ribosomal RNA (rRNA) genes,
respectively. We determined the marked conservation of gene content and sequence
evolutionary rate in the cp genome of four Notopterygium species. Three genes
(psaI, psbI and rpoA) were possibly under positive selection among the four
sampled species. Phylogenetic analysis showed that four Notopterygium species
formed a monophyletic clade with high bootstrap support. However, the
inconsistent interspecific relationships with the genus Notopterygium were
identified between the cp DNA and ITS markers. The incomplete lineage sorting,
convergence evolution or hybridization, gene infiltration and different sampling
strategies among species may have caused the incongruence between the nuclear and
cp DNA relationships. The present results suggested that Notopterygium species
may have experienced a complex evolutionary history and speciation process.
PMID- 28422072
TI - A Little Bug with a Big Bite: Impact of Hemlock Woolly Adelgid Infestations on
Forest Ecosystems in the Eastern USA and Potential Control Strategies.
AB - Hemlock woolly adelgid (Adelges tsugae Annand, HWA) remains the single greatest
threat to the health and sustainability of hemlock in the eastern USA. The loss
of hemlock trees leads to further negative impacts on the diversity and stability
of ecosystems in the eastern part of North America. It is, therefore, urgent to
develop effective control measures to reduce HWA populations and promote overall
hemlock health. Currently available individual and integrated approaches should
continue to be evaluated in the laboratory and in the field along with the
development of other new and innovative methods.
PMID- 28422074
TI - Recent Developments in Fiber Optics Humidity Sensors.
AB - A wide range of applications such as health, human comfort, agriculture, food
processing and storage, and electronic manufacturing, among others, require fast
and accurate measurement of humidity. Sensors based on optical fibers present
several advantages over electronic sensors and great research efforts have been
made in recent years in this field. The present paper reports the current trends
of optical fiber humidity sensors. The evolution of optical structures developed
towards humidity sensing, as well as the novel materials used for this purpose,
will be analyzed. Well-known optical structures, such as long-period fiber
gratings or fiber Bragg gratings, are still being studied towards an enhancement
of their sensitivity. Sensors based on lossy mode resonances constitute a
platform that combines high sensitivity with low complexity, both in terms of
their fabrication process and the equipment required. Novel structures, such as
resonators, are being studied in order to improve the resolution of humidity
sensors. Moreover, recent research on polymer optical fibers suggests that the
sensitivity of this kind of sensor has not yet reached its limit. Therefore,
there is still room for improvement in terms of sensitivity and resolution.
PMID- 28422075
TI - Multisensory System for the Detection and Localization of Peripheral Subcutaneous
Veins.
AB - This paper proposes a multisensory system for the detection and localization of
peripheral subcutaneous veins, as a first step for achieving automatic robotic
insertion of catheters in the near future. The multisensory system is based on
the combination of a SWIR (Short-Wave Infrared) camera, a TOF (Time-Of-Flight)
camera and a NIR (Near Infrared) lighting source. The associated algorithm
consists of two main parts: one devoted to the features extraction from the SWIR
image, and another envisaged for the registration of the range data provided by
the TOF camera, with the SWIR image and the results of the peripheral veins
detection. In this way, the detected subcutaneous veins are mapped onto the 3D
reconstructed surface, providing a full representation of the region of interest
for the automatic catheter insertion. Several experimental tests were carried out
in order to evaluate the capabilities of the presented approach. Preliminary
results demonstrate the feasibility of the proposed design and highlight the
potential benefits of the solution.
PMID- 28422073
TI - Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current
Status and Future Direction.
AB - A sustained and chronically-inflamed environment is characterized by the presence
of heterogeneous inflammatory cellular components, including neutrophils,
macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth
stimulating mediators (inflammatory cytokines and growth factors), chemotactic
factors (chemokines) and genotoxic substances (reactive oxygen species and
nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic
inflammation serves as an intrinsic niche for carcinogenesis and tumor
progression. In this article, we summarize the up-to-date findings regarding
definitive/possible causes and mechanisms of inflammation-related carcinogenesis
derived from experimental and clinical studies. We also propose 10 strategies, as
well as candidate agents for the prevention of inflammation-related
carcinogenesis.
PMID- 28422076
TI - ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using
Zebrafish.
AB - Toxicity is one of the major attrition causes during the drug development
process. In that line, cardio-, neuro-, and hepatotoxicities are among the main
reasons behind the retirement of drugs in clinical phases and post market
withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming
an important tool to assess the toxicity and efficacy of novel drugs. This animal
model has, from early developmental stages, fully functional organs from a
physiological point of view. Thus, drug-induced organ-toxicity can be detected in
larval stages, allowing a high predictive power on possible human drug-induced
liabilities. Hence, zebrafish can bridge the gap between preclinical in vitro
safety assays and rodent models in a fast and cost-effective manner. ZeGlobalTox
is an innovative assay that sequentially integrates in vivo cardio-, neuro-, and
hepatotoxicity assessment in the same animal, thus impacting strongly in the 3Rs
principles. It Reduces, by up to a third, the number of animals required to
assess toxicity in those organs. It Refines the drug toxicity evaluation through
novel physiological parameters. Finally, it might allow the Replacement of
classical species, such as rodents and larger mammals, thanks to its high
predictivity (Specificity: 89%, Sensitivity: 68% and Accuracy: 78%).
PMID- 28422077
TI - Economic Burden of Obesity: A Systematic Literature Review.
AB - Background: The rising prevalence of obesity represents an important public
health issue. An assessment of its costs may be useful in providing
recommendations for policy and decision makers. This systematic review aimed to
assess the economic burden of obesity and to identify, measure and describe the
different obesity-related diseases included in the selected studies. Methods: A
systematic literature search of studies in the English language was carried out
in Medline (PubMed) and Web of Science databases to select cost-of-illness
studies calculating the cost of obesity in a study population aged >=18 years
with obesity, as defined by a body mass index of >=30 kg/m2, for the whole
selected country. The time frame for the analysis was January 2011 to September
2016. Results: The included twenty three studies reported a substantial economic
burden of obesity in both developed and developing countries. There was
considerable heterogeneity in methodological approaches, target populations,
study time frames, and perspectives. This prevents an informative comparison
between most of the studies. Specifically, there was great variety in the
included obesity-related diseases and complications among the studies.
Conclusions: There is an urgent need for public health measures to prevent
obesity in order to save societal resources. Moreover, international consensus is
required on standardized methods to calculate the cost of obesity to improve
homogeneity and comparability. This aspect should also be considered when
including obesity-related diseases.
PMID- 28422078
TI - Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming.
AB - Antivenom therapy is currently the standard practice for treating neuromuscular
dysfunction in snake envenoming. We reviewed the clinical and experimental
evidence-base for the efficacy and effectiveness of antivenom in snakebite
neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction,
and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging
the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the
nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for
neurotoxicity include rodent lethality tests, which are problematic, and in vitro
pharmacological tests such as nerve-muscle preparation studies, that appear to
provide more clinically meaningful information. We searched MEDLINE (from 1946)
and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded
no randomised placebo-controlled trials of antivenom for neuromuscular
dysfunction. There were several randomised and non-randomised comparative trials
that compared two or more doses of the same or different antivenom, and numerous
cohort studies and case reports. The majority of studies available had
deficiencies including poor case definition, poor study design, small sample size
or no objective measures of paralysis. A number of studies demonstrated the
efficacy of antivenom in human envenoming by clearing circulating venom. Studies
of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.)
and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established
neurotoxicity, but early administration may be associated with decreased severity
or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic
neurotoxins, including some cobra species (Naja spp.), provide preliminary
evidence that neurotoxicity may be reversed with antivenom, but placebo
controlled studies with objective outcome measures are required to confirm this.
PMID- 28422080
TI - Study on Temperature and Synthetic Compensation of Piezo-Resistive Differential
Pressure Sensors by Coupled Simulated Annealing and Simplex Optimized Kernel
Extreme Learning Machine.
AB - As a high performance-cost ratio solution for differential pressure measurement,
piezo-resistive differential pressure sensors are widely used in engineering
processes. However, their performance is severely affected by the environmental
temperature and the static pressure applied to them. In order to modify the non
linear measuring characteristics of the piezo-resistive differential pressure
sensor, compensation actions should synthetically consider these two aspects.
Advantages such as nonlinear approximation capability, highly desirable
generalization ability and computational efficiency make the kernel extreme
learning machine (KELM) a practical approach for this critical task. Since the
KELM model is intrinsically sensitive to the regularization parameter and the
kernel parameter, a searching scheme combining the coupled simulated annealing
(CSA) algorithm and the Nelder-Mead simplex algorithm is adopted to find an
optimal KLEM parameter set. A calibration experiment at different working
pressure levels was conducted within the temperature range to assess the proposed
method. In comparison with other compensation models such as the back-propagation
neural network (BP), radius basis neural network (RBF), particle swarm
optimization optimized support vector machine (PSO-SVM), particle swarm
optimization optimized least squares support vector machine (PSO-LSSVM) and
extreme learning machine (ELM), the compensation results show that the presented
compensation algorithm exhibits a more satisfactory performance with respect to
temperature compensation and synthetic compensation problems.
PMID- 28422079
TI - Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates
Endothelial Transient Receptor Potential Vanilloid-Type 1.
AB - The natural product, rutaecarpine (RUT), is the main effective component of
Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has
vasodilation, anticoagulation, and anti-inflammatory activities. However, further
therapeutic applications are limited by its cytotoxicity. Thus, a derivative of
RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that
showed no cytotoxicity toward RAW264.7 macrophages at 20 MUM. In an anti
inflammation experiment, it inhibited the production of nitric oxide (NO) and
tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated RAW264.7
macrophages; cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) induced by
LPS were also downregulated. After 24 h of treatment, F-RUT significantly
inhibited cell migration and invasion of ovarian A2780 cells. Furthermore, F-RUT
promoted expressions of transient receptor potential vanilloid type 1 (TRPV1) and
endothelial (e)NOS in human aortic endothelial cells, and predominantly reduced
the inflammation in ovalbumin/alum-challenged mice. These results suggest that
the novel synthetic F-RUT exerts activities against inflammation and
vasodilation, while displaying less toxicity than its lead compound.
PMID- 28422081
TI - Non-Responsive Feeding Practices, Unhealthy Eating Behaviors, and Risk of Child
Overweight and Obesity in Southeast Asia: A Systematic Review.
AB - Childhood obesity is increasing dramatically in many Southeast Asian countries,
and becoming a significant public health concern. This review summarizes the
evidence on associations between parental feeding practices, child eating
behaviors, and the risk of overweight and obesity in Southeast Asian children 2
12 years old. We systematically searched five electronic academic/research
(PubMed, PsycINFO, ProQuest Nursing, Medline, and CINAHL) databases using the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
statement for peer-reviewed studies published in English between January 2000 and
December 2016. Fourteen observational studies met the inclusion criteria and were
reviewed. Reviewed studies were examined separately for preschool- and school
aged children and revealed that non-responsive parental feeding practices and
unhealthy child eating behaviors were associated with a risk of child overweight
and obesity in several Southeast Asian countries. Nonetheless, due to the small
number of identified studies (n = 14) and because only about half of the
Southeast Asian countries (Thailand, Vietnam, Singapore, the Philippines, and
Malaysia) were represented (5/11) in the examined studies, additional research is
needed to further understand the factors associated with childhood obesity among
children in Southeast Asia to develop interventions that are tailored to the
specific needs of Southeast Asian countries and designed to address practices and
behaviors that may promote childhood obesity.
PMID- 28422083
TI - Nasopharyngeal Carriage and Antimicrobial Susceptibility Patterns of
Streptococcus pneumoniae among Children under Five in Southwest Ethiopia.
AB - Nasopharyngeal carriage of Streptococcus pneumoniae is found to play an important
role in the development and transmission of pneumococcal diseases. In this study,
we assessed the nasopharyngeal carriage, antimicrobial susceptibility patterns
and associated risk factors of S. pneumoniae among children under five. A total
of 361 children under five attending the outpatient department of Shanan Gibe
Hospital in Jimma, Southwest Ethiopia were enrolled from June to September 2014.
Nasopharyngeal specimens were collected using sterile plastic applicator rayon
tipped swab and inoculated on tryptone soy agar supplemented with 5% sheep blood
and 5 ug/mL gentamycin. Antimicrobial susceptibility testing was performed using
the modified disk diffusion method. The overall prevalence of S. pneumoniae
carriage was 43.8% (158/361) among children under five. Resistance to
tetracycline, cotrimoxazole, penicillin, chloramphenicol and erythromycin was
observed in 53.2% (84/158), 43.7% (69/158), 36.1% (57/158), 13.3% (21/158) and
8.9% (14/158) of isolates respectively. Multidrug resistance was seen in 17.7%
(28/158) of isolates. In multivariate logistic regression analysis, children
living with sibling(s) < 5 years old (adjusted odds ratio (AOR) = 1.798; 95%
confidence interval (CI), 1.169-2.766) and malnutrition (AOR = 2.065; 95% CI,
1.239-3.443) were significantly associated with S. pneumoniae carriage. A high
nasopharyngeal carriage of S. pneumoniae was observed among children under five
in Southwest Ethiopia. There should be a strategy to prevent S. pneumoniae
nasopharyngeal colonization and identify the appropriate antibiotic to the
individual child.
PMID- 28422082
TI - Molecular Imprinting of Macromolecules for Sensor Applications.
AB - Molecular recognition has an important role in numerous living systems. One of
the most important molecular recognition methods is molecular imprinting, which
allows host compounds to recognize and detect several molecules rapidly,
sensitively and selectively. Compared to natural systems, molecular imprinting
methods have some important features such as low cost, robustness, high
recognition ability and long term durability which allows molecularly imprinted
polymers to be used in various biotechnological applications, such as
chromatography, drug delivery, nanotechnology, and sensor technology. Sensors are
important tools because of their ability to figure out a potentially large number
of analytical difficulties in various areas with different macromolecular
targets. Proteins, enzymes, nucleic acids, antibodies, viruses and cells are
defined as macromolecules that have wide range of functions are very important.
Thus, macromolecules detection has gained great attention in concerning the
improvement in most of the studies. The applications of macromolecule imprinted
sensors will have a spacious exploration according to the low cost, high
specificity and stability. In this review, macromolecules for molecularly
imprinted sensor applications are structured according to the definition of
molecular imprinting methods, developments in macromolecular imprinting methods,
macromolecular imprinted sensors, and conclusions and future perspectives. This
chapter follows the latter strategies and focuses on the applications of
macromolecular imprinted sensors. This allows discussion on how sensor strategy
is brought to solve the macromolecules imprinting.
PMID- 28422084
TI - An Algorithm for Timely Transmission of Solicitation Messages in RPL for Energy
Efficient Node Mobility.
AB - The IPv6 Routing Protocol for Low Power and Lossy Networks (RPL) was proposed for
various applications of IPv6 low power wireless networks. While RPL supports
various routing metrics and is designed to be suitable for wireless sensor
network environments, it does not consider the mobility of nodes. Therefore,
there is a need for a method that is energy efficient and that provides stable
and reliable data transmission by considering the mobility of nodes in RPL
networks. This paper proposes an algorithm to support node mobility in RPL in an
energy-efficient manner and describes its operating principle based on different
scenarios. The proposed algorithm supports the mobility of nodes by dynamically
adjusting the transmission interval of the messages that request the route based
on the speed and direction of the motion of mobile nodes, as well as the costs
between neighboring nodes. The performance of the proposed algorithm and previous
algorithms for supporting node mobility were examined experimentally. From the
experiment, it was observed that the proposed algorithm requires fewer messages
per unit time for selecting a new parent node following the movement of a mobile
node. Since fewer messages are used to select a parent node, the energy
consumption is also less than that of previous algorithms.
PMID- 28422085
TI - Resonant Rectifier ICs for Piezoelectric Energy Harvesting Using Low-Voltage Drop
Diode Equivalents.
AB - Herein, we present the design technique of a resonant rectifier for piezoelectric
(PE) energy harvesting. We propose two diode equivalents to reduce the voltage
drop in the rectifier operation, a minuscule-drop-diode equivalent (MDDE) and a
low-drop-diode equivalent (LDDE). The diode equivalents are embedded in resonant
rectifier integrated circuits (ICs), which use symmetric bias-flip to reduce the
power used for charging and discharging the internal capacitance of a PE
transducer. The self-startup function is supported by synchronously generating
control pulses for the bias-flip from the PE transducer. Two resonant rectifier
ICs, using both MDDE and LDDE, are fabricated in a 0.18 MUm CMOS process and
their performances are characterized under external and self-power conditions.
Under the external-power condition, the rectifier using LDDE delivers an output
power POUT of 564 MUW and a rectifier output voltage VRECT of 3.36 V with a power
transfer efficiency of 68.1%. Under self-power conditions, the rectifier using
MDDE delivers a POUT of 288 MUW and a VRECT of 2.4 V with a corresponding
efficiency of 78.4%. Using the proposed bias-flip technique, the power extraction
capability of the proposed rectifier is 5.9 and 3.0 times higher than that of a
conventional full-bridge rectifier.
PMID- 28422086
TI - Association Between Secretoglobin Family 3A Member 2 (SCGB3A2) Gene Polymorphisms
and Asthma in a Korean Population.
AB - BACKGROUND Secretoglobin family 3A member 2 (SCGB3A2) plays an important role in
secreting lung surfactant protein, which is a downstream target of thyroid
transcription factor. MATERIAL AND METHODS We investigated whether single
nucleotide polymorphisms (SNPs) of SCGB3A2 gene contribute to susceptibility to
asthma. To explore this possible association, 2 promoter SNPs (rs6882292, 659 G/A
and rs1368408, -112 G/A) and missense SNP (rs151333009, stop codon) were tested
in SCGB3A2 gene in 101 asthma patients and 377 healthy control subjects. SNPStats
was used to obtain odds ratio (OR), 95% confidence intervals (CI), and P value
adjusted for age and sex as covariables. Logistic regression method in each model
(dominant, recessive, and log-additive) was applied to analyze genetic data.
RESULTS rs151333009 SNP showed a monomorphic genotype. Two promoter SNPs
(rs6882292, -659 G/A and rs1368408, -112 G/A) showed significant association with
asthma (rs6882292, OR=2.66, 95% CI=1.42-5.01, p=0.0033 in dominant model,
OR=2.45, 95% CI=1.33-4.54, p=0.0055 in log-additive model; rs1368408, OR=1.59,
95% CI=1.02-2.49, p=0.041 in dominant model, OR=3.02, 95% CI=1.15-7.90, p=0.03 in
recessive model, OR=1.63, 95% CI=1.63, 95% CI=1.12-2.37, p=0.012 in log-additive
model). CONCLUSIONS These results suggest that the promoter SNPs (rs6882292 and
rs1368408) of SCGB3A2 gene may contribute to susceptibility to asthma in a Korean
population.
PMID- 28422087
TI - Clinical comparison of patient outcomes following implantation of trifocal or
bifocal intraocular lenses: a systematic review and meta-analysis.
AB - To assess the visual effects of trifocal intraocular lenses (IOLs) compared to
bifocal IOLs in cataract surgery, a meta-analysis of prospective comparative
clinical trials (including 4 randomized controlled trials and 4 cohorts) was
conducted. The defocus curves showed a better distance-corrected intermediate
visual acuity (VA) for the trifocal group (MD -0.07; 95% CI, -0.10 to -0.05; p <
0.00001), while the VA outcomes showed no significant difference in distance VA
(MD -0.03; 95% CI, -0.06 to 0.01; p = 0.13 for uncorrected distance VA and MD
0.00; 95% CI, -0.01 to 0.01; p = 0.78 for distance-corrected distance VA), near
VA (MD -0.01; 95% CI, -0.07 to 0.04; p = 0.68 for uncorrected near VA and MD
0.01; 95% CI, -0.06 to 0.04; p = 0.66 for distance-corrected near VA) or
refraction between the two groups. Contrast sensitivity and subjective visual
quality yielded less conclusive results. Overall, a patient may achieve better
intermediate VA with a trifocal IOL than with a bifocal IOL without any adverse
effect on distance or near VA. The findings on contrast sensitivity and
subjective visual quality were heterogeneous, with no clear results favoring
either option.
PMID- 28422088
TI - Clustering by fast search and merge of local density peaks for gene expression
microarray data.
AB - Clustering is an unsupervised approach to classify elements based on their
similarity, and it is used to find the intrinsic patterns of data. There are
enormous applications of clustering in bioinformatics, pattern recognition, and
astronomy. This paper presents a clustering approach based on the idea that
density wise single or multiple connected regions make a cluster, in which
density maxima point represents the center of the corresponding density region.
More precisely, our approach firstly finds the local density regions and
subsequently merges the density connected regions to form the meaningful
clusters. This idea empowers the clustering procedure, in which outliers are
automatically detected, higher dense regions are intuitively determined and
merged to form clusters of arbitrary shape, and clusters are identified
regardless the dimensionality of space in which they are embedded. Extensive
experiments are performed on several complex data sets to analyze and compare our
approach with the state-of-the-art clustering methods. In addition, we
benchmarked the algorithm on gene expression microarray data sets for cancer
subtyping; to distinguish normal tissues from tumor; and to classify multiple
tissue data sets.
PMID- 28422090
TI - Surgical treatment in Paget's disease with invasive ductal carcinoma: an
observational study based on SEER.
AB - The aim is to analyse the clinical presentation, treatment and outcomes in
patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with
special emphasis on the role of surgical treatment. Using data obtained by the
Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we
investigated the differences in characteristics, overall survival (OS), and
breast cancer-specific mortality (BCSM) between patients with PD-IDC and those
with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD
IDC had a better prognosis and lower mortality in adjusted analyses. In the
multivariate analysis of cases with PD-IDC, history of ALND was significantly
associated with OS while Her2 status were associated with BCSM. Further, subgroup
analysis demonstrated no difference between surgical treatment subgroups for
either OS or BCSM. The results demonstrated that PD-IDC appears to alter the
association between prognosis and Her2 status. Meanwhile, breast-conserving
surgery with radiotherapy may be a feasible treatment alternative and sentinel
lymph node biopsy should be considered as an appropriate treatment for patients
with PD-IDC.
PMID- 28422089
TI - Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport.
AB - Brown and beige adipocytes combust nutrients for thermogenesis and through their
metabolic activity decrease pro-atherogenic remnant lipoproteins in
hyperlipidemic mice. However, whether the activation of thermogenic adipocytes
affects the metabolism and anti-atherogenic properties of high-density
lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in
response to pharmacological stimulation of thermogenesis linked to increased HDL
levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological
thermogenic activation enhances HDL remodelling, which is associated with
specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic
stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces
reverse cholesterol transport in mice. Mechanistically, we show that
intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL
by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in
liver. Our findings corroborate the notion that high metabolic activity of
thermogenic adipocytes confers atheroprotective properties via increased systemic
cholesterol flux through the HDL compartment.
PMID- 28422091
TI - Male African elephants discriminate and prefer vocalizations of unfamiliar
females.
AB - Gaining information about conspecifics via long-distance vocalizations is crucial
for social and spatially flexible species such as the African elephant (Loxodonta
africana). Female elephants are known to discriminate individuals and kin based
on acoustic cues. Specifically, females approached the loudspeaker exclusively
with playbacks of familiar individuals with high association indexes,
intentionally fusing with their affiliates. For males, which are less bonded,
gathering social information via vocalizations could still have important
implications, but little is known about their vocal discrimination skills. We
experimentally tested the ability of male African elephants to discriminate the
social rumbles of familiar (from the same population) versus unfamiliar females.
Male elephants discriminated and preferentially moved towards the rumbles of
unfamiliar females, showing longer attentive reactions and significantly more
orientating (facing and approaching the speaker) behavior. The increased
orientating response of males towards playbacks of unfamiliar females is converse
to the reaction of female subjects. Our results provide evidence that male
elephants extract social information from vocalizations, yet with a different
intention than females. Accordingly, males might use social cues in vocalizations
to assess mating opportunities, which may involve selection to identify
individuals or kin in order to avoid inbreeding.
PMID- 28422093
TI - Quantum Enhanced Inference in Markov Logic Networks.
AB - Markov logic networks (MLNs) reconcile two opposing schools in machine learning
and artificial intelligence: causal networks, which account for uncertainty
extremely well, and first-order logic, which allows for formal deduction. An MLN
is essentially a first-order logic template to generate Markov networks.
Inference in MLNs is probabilistic and it is often performed by approximate
methods such as Markov chain Monte Carlo (MCMC) Gibbs sampling. An MLN has many
regular, symmetric structures that can be exploited at both first-order level and
in the generated Markov network. We analyze the graph structures that are
produced by various lifting methods and investigate the extent to which quantum
protocols can be used to speed up Gibbs sampling with state preparation and
measurement schemes. We review different such approaches, discuss their
advantages, theoretical limitations, and their appeal to implementations. We find
that a straightforward application of a recent result yields exponential speedup
compared to classical heuristics in approximate probabilistic inference, thereby
demonstrating another example where advanced quantum resources can potentially
prove useful in machine learning.
PMID- 28422092
TI - Hierarchical assembly of centriole subdistal appendages via centrosome binding
proteins CCDC120 and CCDC68.
AB - In animal cells, the centrosome is the main microtubule-organizing centre where
microtubules are nucleated and anchored. The centriole subdistal appendages
(SDAs) are the key structures that anchor microtubules in interphase cells, but
the composition and assembly mechanisms of SDAs are not well understood. Here, we
reveal that centrosome-binding proteins, coiled-coil domain containing (CCDC) 120
and CCDC68 are two novel SDA components required for hierarchical SDA assembly in
human cells. CCDC120 is anchored to SDAs by ODF2 and recruits CEP170 and Ninein
to the centrosome through different coiled-coil domains at its N terminus. CCDC68
is a CEP170-interacting protein that competes with CCDC120 in recruiting CEP170
to SDAs. Furthermore, CCDC120 and CCDC68 are required for centrosome microtubule
anchoring. Our findings elucidate the molecular basis for centriole SDA
hierarchical assembly and microtubule anchoring in human interphase cells.
PMID- 28422094
TI - Erratum: Nonlinear detection of secondary isotopic chemical shifts in NMR through
spin noise.
PMID- 28422095
TI - Structure and Variability of the North Equatorial Current/Undercurrent from
Mooring Measurements at 130 degrees E in the Western Pacific.
AB - The mean structure and variability of the North Equatorial Current/Undercurrent
(NEC/NEUC) are investigated with one-year Acoustic Doppler Current Profilers
measurements from 4 subsurface moorings deployed at 10.5 degrees N, 13 degrees N,
15.5 degrees N, and 18 degrees N along 130 degrees E in the western Pacific. The
strong westward flowing NEC ranges from the sea surface down to 400 m, and the
mean zonal velocity of the NEC at 10.5 degrees N is around -30 cm/s at the depth
of 70 m. Eastward flowing NEUC jets are detected below the NEC at 10.5 degrees N
and 13 degrees N, and the depth of the NEUC could reach at least 900 m. The mean
velocity of the NEUC is around 4.2 cm/s at 800 m. No eastward undercurrents are
observed at 15 degrees N and 18 degrees N. The mooring measurements also reveal a
strong intraseasonal variability of the currents at all 4 mooring sites, and the
period is around 70-120 days. The vertical structure of this intraseasonal
variability varies at different latitudes. The variability of the NEUC jets at
10.5 degrees N and 13 degrees N appears to be dominated by subthermocline
signals, while the variability of the currents at 15.5 degrees N and 18 degrees N
is dominated by surface-intensified signals.
PMID- 28422096
TI - Response to Protocol Review Scenario: Teamwork can go a long way.
PMID- 28422097
TI - Design, analysis and reporting of tumor models.
PMID- 28422098
TI - Treating mouse tumors with microglia.
PMID- 28422099
TI - Characterizing the zebrafish synaptic proteome.
PMID- 28422100
TI - Response to Protocol Review Scenario: Before the amendment.
PMID- 28422101
TI - Response to Protocol Review Scenario: More work upfront to avoid last minute
problems.
PMID- 28422102
TI - Shaping up two-photon imaging in vivo.
PMID- 28422103
TI - C. elegans takes out the trash.
PMID- 28422104
TI - Cas9 cuts to the quick in the cortex.
PMID- 28422105
TI - What role should an IACUC play when a PI's manuscript is on the line?
PMID- 28422106
TI - Mouse models move to Asian markets.
PMID- 28422110
TI - Maximizing survival: lung protective ventilation.
PMID- 28422111
TI - Training mouse pathologists: 15 years of workshops on the pathology of mouse
models of human disease.
PMID- 28422112
TI - Accurate and effective multidrug-resistant Mycobacterium tuberculosis detection
method using gap-filling ligation coupled with high-resolution capillary
electrophoresis-based single strand conformation polymorphism.
AB - Tuberculosis (TB) has severely threatened public health via emerging multidrug
resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis
(MTB) strains. For effective TB treatment, rapid, accurate, and multiplex
detection of drug resistance is extremely important. However, conventional
methods for TB diagnosis are time consuming and have a limited effect on
treatment. Nucleic acid-based molecular detection methods have been developed as
an effective MDR/XDR-TB diagnosis technology. Among the nucleic acid-based
methods, ligation-dependent methods are attractive as MDR/XDR-MTB detection
technologies, but multiplex analysis is limited by the detection method. Although
an electrophoresis-based method is considered for multiple target detection
because it is free from the errors pertaining to hybridization-based systems, the
procedure of multiplex analysis is quite complicated owing to the DNA size-based
separation system. In this study, we report an accurate, rapid, and simple
multiple MDR/XDR-MTB detection technology using gap-filling ligation reaction
coupled with high-resolution capillary electrophoresis-based single-strand
conformation polymorphism. Using this system, rapid and accurate MDR/XDR-MTB
detection is feasible via similar length probes without the complicated step of
probe design. We found that this method could accurately and effectively detect
highly polymorphic regions in specific codons associated with drug resistance.
PMID- 28422113
TI - Increased spontaneous MEG signal diversity for psychoactive doses of ketamine,
LSD and psilocybin.
AB - What is the level of consciousness of the psychedelic state? Empirically,
measures of neural signal diversity such as entropy and Lempel-Ziv (LZ)
complexity score higher for wakeful rest than for states with lower conscious
level like propofol-induced anesthesia. Here we compute these measures for
spontaneous magnetoencephalographic (MEG) signals from humans during altered
states of consciousness induced by three psychedelic substances: psilocybin,
ketamine and LSD. For all three, we find reliably higher spontaneous signal
diversity, even when controlling for spectral changes. This increase is most
pronounced for the single-channel LZ complexity measure, and hence for temporal,
as opposed to spatial, signal diversity. We also uncover selective correlations
between changes in signal diversity and phenomenological reports of the intensity
of psychedelic experience. This is the first time that these measures have been
applied to the psychedelic state and, crucially, that they have yielded values
exceeding those of normal waking consciousness. These findings suggest that the
sustained occurrence of psychedelic phenomenology constitutes an elevated level
of consciousness - as measured by neural signal diversity.
PMID- 28422114
TI - Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose
homeostasis.
PMID- 28422115
TI - Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose
homeostasis.
PMID- 28422116
TI - Skin Cancer: Have melanoma and skin cancer finally met their match?
PMID- 28422117
TI - Ultrahigh Responsivity and Detectivity Graphene-Perovskite Hybrid
Phototransistors by Sequential Vapor Deposition.
AB - In this work, graphene-methylammonium lead iodide (MAPbI3) perovskite hybrid
phototransistors fabricated by sequential vapor deposition are demonstrated.
Ultrahigh responsivity of 1.73 * 107 A W-1 and detectivity of 2 * 1015 Jones are
achieved, with extremely high effective quantum efficiencies of about 108% in the
visible range (450-700 nm). This excellent performance is attributed to the ultra
flat perovskite films grown by vapor deposition on the graphene sheets. The
hybrid structure of graphene covered with uniform perovskite has high exciton
separation ability under light exposure, and thus efficiently generates
photocurrents. This paper presents photoluminescence (PL) images along with
statistical analysis used to study the photo-induced exciton behavior. Both
uniform and dramatic PL intensity quenching has been observed over entire
measured regions, consistently demonstrating excellent exciton separation in the
devices.
PMID- 28422118
TI - Nutrient regulation of beta-cell function: what do islet cell/animal studies tell
us?
AB - Diabetes mellitus is widely recognised as one of the most serious metabolic
diseases worldwide, and its incidence in Asian countries is growing at an
alarming rate. Type 2 diabetes (T2DM) is closely associated with age, sedentary
lifestyle and poor diet. In T2DM, beta-cell dysfunction will occur before
hyperglycaemia develops. Excessive levels of glucose, lipid and various
inflammatory factors interact at the level of the pancreatic islet to promote
beta-cell dysfunction. Pancreatic beta-cell lines have been widely utilised since
the early 1980s and have contributed a large volume of important information
regarding molecular, metabolic and genetic mechanisms that regulate insulin
secretion. The purpose of this review is to describe the origin and
characteristics of the most commonly used beta-cell lines and their contribution
to discovery of fundamental regulatory processes that control insulin production
and release. Pancreatic islets obtained from rodents as well as other animals
have additionally provided information on the architecture and three-dimensional
design of this endocrine tissue that allows precise regulation of hormone
release. Understanding the nature of failure of physiologic and metabolic
processes leading to insufficient insulin release and subsequent diabetes has
allowed development of novel anti-diabetic therapeutics, now in common use,
worldwide.
PMID- 28422120
TI - Trends of increases in potential risk factors and prevalence rates of diabetes
mellitus in Thailand.
AB - Over the past three decades, undernutrition in Thailand has drastically reduced
by over seven times. However, since 1995 the number of patients afflicted with
non-communicable diseases, such as diabetes mellitus, has rapidly increased, even
among the young. Unhealthy life styles due to urbanization are a major reason for
this increase. Less physical activity and low consumption of fruits and
vegetables, as well as high consumption of added free sugar, are common. Every
year, the Thai people increase their consumption of energy from fat and protein,
while lowering their intake of energy from complex carbohydrates. Per capita and
on average, a Thai individual consumes up to 20% of total energy from added free
sugar. Barker's hypothesis and Developmental Origins of Health and Disease
hypothesis (DOHaD) can partially explain the increase in diabetes mellitus at
this rapid rate. To alleviate the problem, the main strategy has been consumer
education to reduce diabetes mellitus prevalence. Sugar elimination from infant
formula is mandatory and sugar taxation is being considered. Simplified nutrition
labeling is voluntarily as part of consumer education, as well as encouraging
food industries to produce healthier food products. Currently, a multi-sectoral
approach is used for alleviating diabetes mellitus in Thailand.
PMID- 28422119
TI - Current lifestyle factors that increase risk of T2DM in China.
AB - The Report on the Status of Nutrition and Chronic Diseases of Chinese residents
(2015) indicated that the prevalence of diabetes was 9.7% among adults aged ?18
years, which markedly increased from 2.6% in 2002 within 10 years. In addition to
the social economic factors, transitions in food consumption, behavioral and
lifestyle playing the important roles in the fast increase of type 2 diabetes
mellitus (T2DM). In 2010-2012, the cereal food consumption of Chinese residents
was 337 g/d, vegetables consumption 269 g/d, fruit consumption 41 g/d, legume and
legume products 11 g/d, dairy and dairy products consumption 25 g/d, meat
consumption 90 g/d, edible oil consumption 42 g/d and dietary fiber 10.8 g/d. The
traditional Chinese dietary pattern (high consumption of rice, pork and
vegetables) is shifting towards a dietary pattern with high consumption of meats
and edible oil but low consumption of cereals and vegetables. Smoking, breakfast
omitting and high consumption of sugar-sweetened beverages became popular.
Insufficient physical activity rate was 31.7%. Less sleep duration and poorer
sleep quality was also common for Chinese residents. Concerning early life
factors, residents exposed to the Chinese famine (1959-1961) during fetal life
and childhood had an increased risk of hyperglycemia. As a conclusion, current
unhealthy lifestyle has inversely effect on the incidence and development of
T2DM, especially for the increased intake of fat and carbohydrate, the transition
of dietary pattern, the extension of sedentary time and the increasing rate of
obesity. Lifestyle management should be taken seriously as a part of diabetes
prevention.
PMID- 28422121
TI - A decrease in blood cholesterol after gastrostomy could impact survival in ALS.
AB - Although the global benefits of gastrostomy have been proven in amyotrophic
lateral sclerosis (ALS), the impact on biological parameters has not been
explored yet. The aim of this preliminary work was to evaluate the modification
of biological parameters in patients with ALS undergoing gastrostomy. We
retrospectively collected clinical and biological data from 44 patients having
undergone gastrostomy at three time points (T0, T1 and T2: before, at the time of
and after gastrostomy). We examined the relationship between the biological
parameters and disease progression. Variations of the concentrations of total
cholesterol significantly differed before (T1-T0) vs those after gastrostomy (T2
T1; P=0.0044). The variations of total cholesterol and low-density lipoprotein
cholesterol concentrations after gastrostomy were negatively associated with
survival (P=0.0002). This study showed for the first time that patients with ALS
fed quite exclusively by gastrostomy had decreased blood cholesterol after
gastrostomy. We suggest that a restoration of normal lipid metabolism should be
planned in patients with ALS.
PMID- 28422122
TI - Infant milk fat droplet size and coating affect postprandial responses in healthy
adult men: a proof-of-concept study.
AB - BACKGROUND/OBJECTIVES: Fat droplets in human milk (HM) are larger and surrounded
by a phospholipid membrane compared with infant milk formulas (IMF). Since the
physical structure of fat droplets might affect digestion and postprandial
metabolism, an IMF was developed more mimicking HM lipid structure than current
IMF. SUBJECTS/METHODS: A randomised, double-blind, crossover study was performed
in 29 fasted healthy men (aged 18-25 years, BMI: 18-25 kg/m2) to compare 5-hour
postprandial responses after consumption of an experimental IMF (Concept,
Nuturis) with a current IMF (Control). RESULTS: Postprandial triacylglycerol
(TAG) concentrations tended to increase faster after intake of Concept IMF
(P=0.054), but peaked 3 h after intakes at similar concentrations. ApoB48
increased steadily and peaked 3 h after consumption. Increases in plasma glucose
concentrations were comparable, but peak concentrations were reached faster after
consumption of Concept IMF (P<0.05). Peak insulin concentrations were higher and
reached earlier after intake of Concept IMF, causing a sharper decremental
glucose rebound (P<0.05) and an earlier time to nadir in non-esterified fatty
acid (NEFA) concentrations (P<0.01). Changes in plasma amino acids (AA), apoB100
and apoA1 were comparable. The incremental or decremental areas under-the-curve
did not differ between Concept and Control IMF. Satiety scores and changes in the
satiety hormones ghrelin and peptide YY were comparable, while cholecystokinin
responses were earlier and higher after consumption of Control IMF (P<0.05).
CONCLUSIONS: This proof-of-concept study suggests that fats and carbohydrates
from the Concept IMF with larger and phospholipid-coated fat droplets are more
rapidly absorbed than those from the current IMF.
PMID- 28422123
TI - Role of lifestyle factors in the epidemic of diabetes: lessons learnt from India.
AB - The prevalence of type 2 diabetes (T2D) is increasing steadily globally with the
largest increases occurring in developing countries like India. This is
attributed to the changes in the lifestyle factors, including physical inactivity
and unhealthy diet, both of which are modifiable. Existing evidence suggests that
increasing physical activity reduces the risk of T2D. Improving the built
environment can make it more conducive to people to increase physical activity.
There is also a rapid nutrition transition with consumption of diets with higher
intake of refined grains, higher fat, increased consumption of sugar and
sweetened beverages, and lower intake of fruits and vegetables. A multisectoral
approach promoting healthier diets and increasing physical activity can help in
slowing down the diabetic epidemic. However, this requires political will to make
necessary policy changes, as well as empowerment of the community, if the
preventive measures are to be sustainable and scalable.
PMID- 28422124
TI - Prevalence of type 2 diabetes and its complications in India and economic costs
to the nation.
AB - Diabetes, a major lifestyle disorder, has become a global burden, and the
prevalence rates are rising steeply in developing economies. Rapid socioeconomic
transition with urbanization and industrialization are the main causes for the
global diabetes epidemic. Among developing economies, the highest increase in
number of people with diabetes is in China followed by India. In India, the
epidemic of diabetes continue to increase and is experiencing a shift in diabetes
prevalence from urban to rural areas, the affluent to the less privileged and
from older to younger people. Diabetes is a progressive disorder leading to
complications, which are broadly divided into small vessel or microvascular
disease and large vessel or macrovascular disease. Microvascular complications
affect the inner part of the eye-the retina known as diabetic retinopathy, the
kidney termed as diabetic nephropathy and the peripheral nerves termed as
diabetic neuropathy. The macrovascular complications affect the heart, the brain
and the peripheral arteries termed as cardiovascular disease, cerebrovascular
disease and peripheral vascular disease, respectively. Given the lifelong
expenditure associated with diabetes and its complications, individuals, families
and the society are unable to cope with the economic, emotional and social
disease burden due to diabetes. The economic burden of diabetes can be reduced by
providing universal healthcare coverage, access to affordable medicines and early
detection and treatment of the disorder. This emphasizes the need for a multi
prolonged strategy to minimize the burden of diabetes and its complications.
PMID- 28422125
TI - Running exercise strengthens the intervertebral disc.
AB - There is currently no evidence that the intervertebral discs (IVDs) can respond
positively to exercise in humans. Some authors have argued that IVD metabolism in
humans is too slow to respond anabolically to exercise within the human lifespan.
Here we show that chronic running exercise in men and women is associated with
better IVD composition (hydration and proteoglycan content) and with IVD
hypertrophy. Via quantitative assessment of physical activity we further find
that accelerations at fast walking and slow running (2 m/s), but not high-impact
tasks, lower intensity walking or static positions, correlated to positive IVD
characteristics. These findings represent the first evidence in humans that
exercise can be beneficial for the IVD and provide support for the notion that
specific exercise protocols may improve IVD material properties in the spine. We
anticipate that our findings will be a starting point to better define exercise
protocols and physical activity profiles for IVD anabolism in humans.
PMID- 28422126
TI - Adrenergic-mediated loss of splenic marginal zone B cells contributes to
infection susceptibility after stroke.
AB - Infection is a major complication of acute stroke and causes increased mortality
and morbidity; however, current interventions do not prevent infection and
improve clinical outcome in stroke patients. The mechanisms that underlie
susceptibility to infection in these patients are unclear. Splenic marginal zone
(MZ) B cells are innate-like lymphocytes that provide early defence against
bacterial infection. Here we show experimental stroke in mice induces a marked
loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression
of circulating IgM. These deficits are accompanied by spontaneous bacterial lung
infection. IgM levels are similarly suppressed in stroke patients. beta
adrenergic receptor antagonism after experimental stroke prevents loss of splenic
MZ B cells, preserves IgM levels, and reduces bacterial burden. These findings
suggest that adrenergic-mediated loss of MZ B cells contributes to the infection
prone state after stroke and identify systemic B-cell disruption as a target for
therapeutic manipulation.
PMID- 28422127
TI - Differential Control of Asexual Development and Sterigmatocystin Biosynthesis by
a Novel Regulator in Aspergillus nidulans.
AB - The filamentous fungus Aspergillus nidulans primarily reproduces by forming
asexual spores called conidia and produces the mycotoxin sterigmatocystin (ST),
the penultimate precursor of aflatoxins. It has been known that asexual
development and ST production are tightly co-regulated by various regulatory
inputs. Here, we report that the novel regulator AslA with a C2H2 domain
oppositely regulates development and ST biosynthesis. Nullifying aslA resulted in
defective conidiation and reduced expression of brlA encoding a key activator of
asexual development, which indicates that AslA functions as an upstream activator
of brlA expression. aslA deletion additionally caused enhanced ST production and
expression of aflR encoding a transcriptional activator for ST biosynthetic
genes, suggesting that AslA functions as an upstream negative regulator of aflR.
Cellular and molecular studies showed that AslA has a trans-activation domain and
is localized in the nuclei of vegetative and developing cells but not in spores,
indicating that AslA is likely a transcription factor. Introduction of the aslA
homologs from distantly-related aspergilli complemented the defects caused by
aslA null mutation in A. nidulans, implying a functional conservancy of AslA. We
propose that AslA is a novel regulator that may act at the split control point of
the developmental and metabolic pathways.
PMID- 28422129
TI - GaAs1-xBix/GaNyAs1-y type-II quantum wells: novel strain-balanced
heterostructures for GaAs-based near- and mid-infrared photonics.
AB - The potential to extend the emission wavelength of photonic devices further into
the near- and mid-infrared via pseudomorphic growth on conventional GaAs
substrates is appealing for a number of communications and sensing applications.
We present a new class of GaAs-based quantum well (QW) heterostructure that
exploits the unusual impact of Bi and N on the GaAs band structure to produce
type-II QWs having long emission wavelengths with little or no net strain
relative to GaAs, while also providing control over important laser loss
processes. We theoretically and experimentally demonstrate the potential of GaAs1
xBix/GaNyAs1-y type-II QWs on GaAs and show that this approach offers optical
emission and absorption at wavelengths up to ~3 um utilising strain-balanced
structures, a first for GaAs-based QWs. Experimental measurements on a prototype
GaAs0.967Bi0.033/GaN0.062As0.938 structure, grown via metal-organic vapour phase
epitaxy, indicate good structural quality and exhibit both photoluminescence and
absorption at room temperature. The measured photoluminescence peak wavelength of
1.72 MUm is in good agreement with theoretical calculations and is one of the
longest emission wavelengths achieved on GaAs to date using a pseudomorphically
grown heterostructure. These results demonstrate the significant potential of
this new class of III-V heterostructure for long-wavelength applications.
PMID- 28422128
TI - Epidemiology of 45,616 suspect cases of Hand, Foot and Mouth Disease in
Chongqing, China, 2011-2015.
AB - Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large
sample size or evaluation of detection for more enterovirus serotypes are not
well investigated in Chongqing of China. 45,616 suspect HFMD patients were
prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases
over a 5-year period (January 2011 to December 2015). Their epidemiological,
clinical, and laboratory data were extracted and stratified by month, age, sex,
disease severity, and enterovirus serotype. Subsequently 292 non-EV-A71/CV-A16
HFMD confirmed cases were randomly selected in three consecutive outbreaks to
detect CV-A6 and CV-A10, using RT-PCR. Results showed that the HFMD epidemic
peaked in early summer and autumn. The median age of onset was 2.45 years with a
male-to-female ratio of 1.54:1, and with children under 5 years of age accounting
for 92.54% of all confirmed cases. EV-A71 and CV-A16 infection accounted for only
36.05% (7793/21615) of total confirmed cases while EV-A71 accounted for 59.64%
(232/389) of severe cases. Importantly, the proportion of EV-A71 infection
generally increased with age which showed rapid growth in severe cases. CV-A6 and
CV-A10 were tested positive in Chongqing, but CV-A6 had greater positive rates of
62.33% while CV-A10 had 4.79% in non-EV-A71/CV-A16 HFMD confirmed cases.
PMID- 28422130
TI - Assessment of metabolic phenotypic variability in children's urine using 1H NMR
spectroscopy.
AB - The application of metabolic phenotyping in clinical and epidemiological studies
is limited by a poor understanding of inter-individual, intra-individual and
temporal variability in metabolic phenotypes. Using 1H NMR spectroscopy we
characterised short-term variability in urinary metabolites measured from 20
children aged 8-9 years old. Daily spot morning, night-time and pooled (50:50
morning and night-time) urine samples across six days (18 samples per child) were
analysed, and 44 metabolites quantified. Intraclass correlation coefficients
(ICC) and mixed effect models were applied to assess the reproducibility and
biological variance of metabolic phenotypes. Excellent analytical reproducibility
and precision was demonstrated for the 1H NMR spectroscopic platform (median CV
7.2%). Pooled samples captured the best inter-individual variability with an ICC
of 0.40 (median). Trimethylamine, N-acetyl neuraminic acid, 3-hydroxyisobutyrate,
3-hydroxybutyrate/3-aminoisobutyrate, tyrosine, valine and 3-hydroxyisovalerate
exhibited the highest stability with over 50% of variance specific to the child.
The pooled sample was shown to capture the most inter-individual variance in the
metabolic phenotype, which is of importance for molecular epidemiology study
design. A substantial proportion of the variation in the urinary metabolome of
children is specific to the individual, underlining the potential of such data to
inform clinical and exposome studies conducted early in life.
PMID- 28422131
TI - Variants in CPLX1 in two families with autosomal-recessive severe infantile
myoclonic epilepsy and ID.
AB - For a large number of individuals with intellectual disability (ID), the
molecular basis of the disorder is still unknown. However, whole-exome sequencing
(WES) is providing more and more insights into the genetic landscape of ID. In
the present study, we performed trio-based WES in 311 patients with unsolved ID
and additional clinical features, and identified homozygous CPLX1 variants in
three patients with ID from two unrelated families. All displayed marked
developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar
cleft in addition. The encoded protein, complexin 1, is crucially involved in
neuronal synaptic regulation, and homozygous Cplx1 knockout mice have the
earliest known onset of ataxia seen in a mouse model. Recently, a homozygous
truncating variant in CPLX1 was suggested to be causative for migrating epilepsy
and structural brain abnormalities. ID was not reported although it cannot be
completely ruled out. However, the currently limited knowledge on CPLX1 suggests
that loss of complexin 1 function may lead to a complex but variable clinical
phenotype, and our findings encourage further investigations of CPLX1 in patients
with ID, developmental delay and myoclonic epilepsy to unravel the phenotypic
spectrum of carriers of CPLX1 variants.
PMID- 28422132
TI - Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG
and 16q24.3 microdeletion syndromes: 12 new cases.
AB - 16q24 deletion involving the ANKRD11 gene, ranging from 137 kb to 2 Mb, have been
associated with a microdeletion syndrome characterized by variable cognitive
impairment, autism spectrum disorder, facial dysmorphisms with dental anomalies,
brain abnormalities essentially affecting the corpus callosum and short stature.
On the other hand, patients carrying either deletions encompassing solely ANKRD11
or its loss-of-function variants were reported in association with the KBG
syndrome, characterized by a very similar phenotype, including mild-to-moderate
intellectual disability, short stature and macrodontia of upper incisors, with
inter and intrafamilial variability. To assess whether the haploinsufficiency of
ANKRD11-flanking genes, such as ZFPM1, CDH15 and ZNF778, contributed to either
the severity of the neurological impairment or was associated with other clinical
features, we collected 12 new cases with a 16q24.2q24.3 deletion (de novo in 11
cases), ranging from 343 kb to 2.3 Mb. In 11 of them, the deletion involved the
ANKRD11 gene, whereas in 1 case only flanking genes upstream to it were deleted.
By comparing the clinical and genetic features of our patients with those
previously reported, we show that the severity of the neurological phenotype and
the frequency of congenital heart defects characterize the deletions that,
besides ANKRD11, contain ZFPM1, CDH15 and ZNF778 as well. Moreover, the presence
of thrombocytopenia and astigmatism should be taken into account to distinguish
between 16q24 microdeletion syndrome and KBG syndrome. The single patient not
deleted for ANKRD11, whose phenotype is characterized by milder psychomotor
delay, cardiac congenital malformation, thrombocytopenia and astigmatism,
confirms all this data.
PMID- 28422133
TI - Gene-set analysis shows association between FMRP targets and autism spectrum
disorder.
AB - Autism spectrum disorder (ASD) is a heterogeneous group of disorders
characterized by problems with social interaction, communication, and repetitive
and restricted behavior. Despite its high heritability and the substantial
progress made in elucidating genetic associations, the corresponding biological
mechanisms are largely unknown. Our objective is to investigate the contribution
of common genetic variation to biological pathways functionally involved in ASD.
We conducted gene-set analyses to identify ASD-associated functional biological
pathways using the statistical tools MAGMA and INRICH. Gene-set selection was
based on previously reported associations with psychiatric disorders and resulted
in testing of specific synaptic and glial sets, a glutamate pathway gene-set,
mitochondrial gene-sets and gene-sets consisting of fragile X mental retardation
protein (FMRP) targets. In total 32 gene-sets were tested. We used Psychiatric
Genomics Consortium genome-wide association studies summary statistics of ASD.
The study is based on the largest ASD sample to date (N=5305). We found one
significantly associated gene-set consisting of FMRP-targeting transcripts
(MAGMA: p corr.=0.014, INRICH: p corr.=0.031; all competitive P-values). The
results indicate the involvement of FMRP-targeted transcripts in ASD in common
genetic variation. This novel finding is in line with the literature as FMRP has
been linked to fragile X syndrome, ASD and cognitive development in whole-exome
sequencing and copy number variant studies. This gene-set has also been linked to
Schizophrenia suggesting that FMRP-targeted transcripts might be involved in a
general mechanism with shared genetic etiology between psychiatric disorders.
PMID- 28422134
TI - Genetic structure and signatures of selection in grey reef sharks (Carcharhinus
amblyrhynchos).
AB - With overfishing reducing the abundance of marine predators in multiple marine
ecosystems, knowledge of genetic structure and local adaptation may provide
valuable information to assist sustainable management. Despite recent
technological advances, most studies on sharks have used small sets of neutral
markers to describe their genetic structure. We used 5517 nuclear single
nucleotide polymorphisms (SNPs) and a mitochondrial DNA (mtDNA) gene to
characterize patterns of genetic structure and detect signatures of selection in
grey reef sharks (Carcharhinus amblyrhynchos). Using samples from Australia,
Indonesia and oceanic reefs in the Indian Ocean, we established that large
oceanic distances represent barriers to gene flow, whereas genetic
differentiation on continental shelves follows an isolation by distance model. In
Australia and Indonesia differentiation at nuclear SNPs was weak, with coral
reefs acting as stepping stones maintaining connectivity across large distances.
Differentiation of mtDNA was stronger, and more pronounced in females, suggesting
sex-biased dispersal. Four independent tests identified a set of loci putatively
under selection, indicating that grey reef sharks in eastern Australia are likely
under different selective pressures to those in western Australia and Indonesia.
Genetic distances averaged across all loci were uncorrelated with genetic
distances calculated from outlier loci, supporting the conclusion that different
processes underpin genetic divergence in these two data sets. This pattern of
heterogeneous genomic differentiation, suggestive of local adaptation, has
implications for the conservation of grey reef sharks; furthermore, it highlights
that marine species showing little genetic differentiation at neutral loci may
exhibit patterns of cryptic genetic structure driven by local selection.
PMID- 28422136
TI - The relationship between climate change and the endangered rainforest shrub
Triunia robusta (Proteaceae) endemic to southeast Queensland, Australia.
AB - Threatened species in rainforests may be vulnerable to climate change, because of
their potentially narrow thermal tolerances, small population sizes and
restricted distributions. This study modelled climate induced changes on the
habitat distribution of the endangered rainforest plant Triunia robusta, endemic
to southeast Queensland, Australia. Species distribution models were developed
for eastern Australia at 250 m grids and southeast Queensland at 25 m grids using
ground-truthed presence records and environmental predictor data. The species'
habitat distribution under the current climate was modelled, and the future
potential habitat distributions were projected for the epochs 2030, 2050 and
2070. The eastern Australia model identified several spatially disjunct, broad
habitat areas of coastal eastern Australia consistent with the current
distribution of rainforests, and projected a southward and upslope contraction
driven mainly by average temperatures exceeding current range limits. The
southeast Queensland models suggest a dramatic upslope contraction toward
locations where the majority of known populations are found. Populations located
in the Sunshine Coast hinterland, consistent with past rainforest refugia, are
likely to persist long-term. Upgrading the level of protection for less formal
nature reserves containing viable populations is a high priority to better
protect refugial T. robusta populations with respect to climate change.
PMID- 28422135
TI - Genomic evidence of hybridization between two independent invasions of European
green crab (Carcinus maenas) in the Northwest Atlantic.
AB - Invasive species have been associated with significant negative impacts in their
introduced range often outcompeting native species, yet the long-term
evolutionary dynamics of biological invasions are not well understood.
Hybridization, either among waves of invasion or between native and introduced
populations, could alter the ecological and evolutionary impacts of invasions yet
has rarely been studied in marine invasive species. The European green crab
(Carcinus maenas) invaded eastern North America twice from northern and southern
locations in its native range. Here we examine the frequency of hybridization
among these two distinct invasions at locations from New Jersey, USA to
Newfoundland, Canada using restriction-site-associated DNA sequencing (RAD-seq),
microsatellite loci and cytochrome c oxidase subunit I mitochondrial DNA (mtDNA)
sequences. We used Bayesian clustering and hybrid assignment analyses to
investigate hybridization between the northern and southern populations. Of the
samples analyzed, six locations contained at least one hybrid individual, while
two locations were characterized by extensive hybridization, with 95% of
individuals collected from Placentia Bay, Newfoundland being hybrids (mostly F2)
and 90% of individuals from Kejimkujik, Nova Scotia being classified as hybrids,
mostly backcrosses to the northern ecotype. The presence of both F2 hybrids and
backcrossed individuals suggests that these hybrids are viable and introgression
is occurring between invasions. Our results provide insight into the demographic
and evolutionary consequences of hybridization between independent invasions, and
will inform the management of green crabs in eastern North America.
PMID- 28422137
TI - Effective in vivo therapeutic IgG antibody against VP3 of enterovirus 71 with
receptor-competing activity.
AB - Passive immunization is an effective option for treatment against hand, foot and
mouth disease caused by EV71, especially with cross-neutralizing IgG monoclonal
antibodies. In this study, an EV71-specific IgG2a antibody designated 5H7 was
identified and characterized. 5H7 efficiently neutralizes the major EV71
genogroups (A, B4, C2, C4). The conformational epitope of 5H7 was mapped to the
highly conserved amino acid position 74 on VP3 capsid protein using escape
mutants. Neutralization with 5H7 is mediated by the inhibition of viral
attachment, as revealed by virus-binding and post-attachment assays. In a
competitive pull-down assay with SCARB2, 5H7 blocks the receptor-binding site on
EV71 for virus neutralization. Passive immunization of chimeric 5H7 protected
100% of two-week-old AG129 mice from lethal challenge with an EV71 B4 strain for
both prophylactic and therapeutic treatments. In contrast, 10D3, a previously
reported neutralizing antibody that takes effect after virus attachment, could
only confer prophylactic protection. These results indicate that efficient
interruption of viral attachment is critical for effective therapeutic activity
with 5H7. This report documents a novel universal neutralizing IgG antibody for
EV71 therapeutics and reveals the underlying mechanism.
PMID- 28422139
TI - High pesticide risk to honey bees despite low focal crop pollen collection during
pollination of a mass blooming crop.
AB - Honey bees provide critical pollination services for many agricultural crops.
While the contribution of pesticides to current hive loss rates is debated,
remarkably little is known regarding the magnitude of risk to bees and mechanisms
of exposure during pollination. Here, we show that pesticide risk in recently
accumulated beebread was above regulatory agency levels of concern for acute or
chronic exposure at 5 and 22 of the 30 apple orchards, respectively, where we
placed 120 experimental hives. Landscape context strongly predicted focal crop
pollen foraging and total pesticide residues, which were dominated by fungicides.
Yet focal crop pollen foraging was a poor predictor of pesticide risk, which was
driven primarily by insecticides. Instead, risk was positively related to
diversity of non-focal crop pollen sources. Furthermore, over 60% of pesticide
risk was attributed to pesticides that were not sprayed during the apple bloom
period. These results suggest the majority of pesticide risk to honey bees
providing pollination services came from residues in non-focal crop pollen,
likely contaminated wildflowers or other sources. We suggest a greater
understanding of the specific mechanisms of non-focal crop pesticide exposure is
essential for minimizing risk to bees and improving the sustainability of grower
pest management programs.
PMID- 28422138
TI - Abnormal resting-state functional connectivity in the orbitofrontal cortex of
heroin users and its relationship with anxiety: a pilot fNIRS study.
AB - Drug addiction is widely linked to the orbitofrontal cortex (OFC), which is
essential for regulating reward-related behaviors, emotional responses, and
anxiety. Over the past two decades, neuroimaging has provided significant
contributions revealing functional and structural alternations in the brains of
drug addicts. However, the underlying neural mechanism in the OFC and its
correlates with drug addiction and anxiety still require further elucidation. We
first presented a pilot investigation to examine local networks in OFC regions
through resting-state functional connectivity (rsFC) using functional near
infrared spectroscopy (fNIRS) from eight abstinent addicts in a heroin-dependent
group (HD) and seven subjects in a control group (CG). We discovered that the HDs
manifested enhanced interhemispheric correlation and rsFC. Moreover, small
worldness was explored in the brain networks. In addition to the altered rsFC in
the OFC networks, our examinations demonstrated associations in the functional
connectivity between the left inferior frontal gyrus and other OFC regions
related to anxiety in the HDs. The study provides important preliminary evidence
of the complex OFC networks in heroin addiction and suggests neural correlates of
anxiety. It opens a window in application of fNIRS to predict psychiatric
trajectories and may create new insights into neural adaptations resulting from
chronic opiate intake.
PMID- 28422140
TI - The evolutionary history of bears is characterized by gene flow across species.
AB - Bears are iconic mammals with a complex evolutionary history. Natural bear
hybrids and studies of few nuclear genes indicate that gene flow among bears may
be more common than expected and not limited to polar and brown bears. Here we
present a genome analysis of the bear family with representatives of all living
species. Phylogenomic analyses of 869 mega base pairs divided into 18,621 genome
fragments yielded a well-resolved coalescent species tree despite signals for
extensive gene flow across species. However, genome analyses using different
statistical methods show that gene flow is not limited to closely related species
pairs. Strong ancestral gene flow between the Asiatic black bear and the ancestor
to polar, brown and American black bear explains uncertainties in reconstructing
the bear phylogeny. Gene flow across the bear clade may be mediated by
intermediate species such as the geographically wide-spread brown bears leading
to large amounts of phylogenetic conflict. Genome-scale analyses lead to a more
complete understanding of complex evolutionary processes. Evidence for extensive
inter-specific gene flow, found also in other animal species, necessitates
shifting the attention from speciation processes achieving genome-wide
reproductive isolation to the selective processes that maintain species
divergence in the face of gene flow.
PMID- 28422141
TI - Erratum: Maternally expressed NLRP2 links the subcortical maternal complex (SCMC)
to fertility, embryogenesis and epigenetic reprogramming.
PMID- 28422143
TI - Dissecting the genetic architecture of Fusarium verticillioides seed rot
resistance in maize by combining QTL mapping and genome-wide association
analysis.
AB - Fusarium verticillioides can be transmitted via seeds and cause systemic
infection in maize (Zea mays L.); its mycotoxin has harmful effects on animal and
human health. We combined QTL mapping in recombinant inbred line (RIL)
populations with a genome-wide association study (GWAS) of 217 diverse maize
lines using 224,152 single nucleotide polymorphisms (SNPs) under controlled
conditions to determine the genetic architecture of F. verticillioides seed rot
(FSR) resistance. Our study identified 8 quantitative trait loci (QTLs) and 43
genes associated with 57 SNPs that were correlated with FSR resistance through
linkage mapping and GWAS, respectively. Among these, there were three candidate
genes, namely GRMZM2G0081223, AC213654.3_FG004, and GRMZM2G099255, which were
detected in both linkage mapping and GWAS. Furthermore, the near-isogenic lines
(NILs) containing GRMZM2G0081223, which also had a susceptible parent background,
were found to have a significantly improved level of resistance. In addition, the
expression profile of the three candidate genes revealed that they all respond to
the infection following inoculation with F. verticillioides. These genetic
analyses indicate that FSR resistance is controlled by loci with minor effect,
and the polymerization breeding of lines with beneficial alleles and candidate
genes could improve FSR resistance in maize.
PMID- 28422142
TI - G protein-coupled KISS1 receptor is overexpressed in triple negative breast
cancer and promotes drug resistance.
AB - Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor
alpha, progesterone receptor and human epidermal growth factor receptor 2 (HER2).
TNBC patients lack targeted therapies, as they fail to respond to endocrine and
anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and
survival is limited due to the development of resistance to available
chemotherapies and resultant metastases. The mechanisms regulating tumor
resistance are poorly understood. Here we demonstrate that the G protein-coupled
kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells. KISS1R binds
kisspeptins, peptide products of the KISS1 gene and in numerous cancers, this
signaling pathway plays anti-metastatic roles. However, in TNBC, KISS1R promotes
tumor invasion. We show that KISS1 and KISS1R mRNA and KISS1R protein are
upregulated in TNBC tumors, compared to normal breast tissue. KISS1R signaling
promotes drug resistance by increasing the expression of efflux drug transporter,
breast cancer resistance protein (BCRP) and by inducing the activity and
transcription of the receptor tyrosine kinase, AXL. BCRP and AXL transcripts are
elevated in TNBC tumors, compared to normal breast, and TNBC tumors expressing
KISS1R also express AXL and BCRP. Thus, KISS1R represents a potentially novel
therapeutic target to restore drug sensitivity in TNBC patients.
PMID- 28422144
TI - Risk and Prediction of Sudden Cardiac Death and Ventricular Arrhythmias for
Patients with Atrial Fibrillation - A Nationwide Cohort Study.
AB - Sudden cardiac death (SCD) is the most devastating manifestation of ventricular
arrhythmias (VAs), and is the leading cause of mortality among atrial
fibrillation (AF) patients. The goal of the present study was to investigate the
incidence of SCD/VAs amongst patients with and without AF. We also aimed to
identify important risk factors of SCD/VAs among AF patients. Using the "National
Health Insurance Research Database" in Taiwan, a total of 352,656 AF and 352,656
non-AF patients without antecedent SCD/VAs were identified. The annual risk of
SCD/VAs was higher in AF than non-AF groups (0.97% versus 0.47%) with an adjusted
hazard ratio (HR) of 1.64. The increased risk of SCD/VAs in AF patients was
consistently observed in different age strata, various comorbidities and patients
without use of class I/III anti-arrhythmic drugs or digoxin. Among AF patients,
age >=75 years, congestive heart failure, hypertension, diabetes mellitus,
previous stroke/transient ischemic attack, vascular diseases, chronic kidney
disease and chronic obstructive pulmonary disease were important risk factors for
SCD/VAs. In conclusion, the risk of SCD/VAs amongst AF patients was 1.64-fold
higher compared to non-AF patients, which was associated with the number of
clinical risk factors associated with the particular AF patient.
PMID- 28422145
TI - Compromised External Validity: Federally Produced Cannabis Does Not Reflect Legal
Markets.
AB - As the most widely used illicit drug worldwide, and as a source of numerous under
studied pharmacologically-active compounds, a precise understanding of
variability in psychological and physiological effects of Cannabis varieties is
essential. The National Institute on Drug Abuse (NIDA) is designated as the sole
legal producer of Cannabis for use in US research studies. We sought to compare
the chemical profiles of Cannabis varieties that are available to consumers in
states that have state-legalized use versus what is available to researchers
interested in studying the plant and its effects. Our results demonstrate that
the federally-produced Cannabis has significantly less variety and lower
concentrations of cannabinoids than are observed in state-legal U.S.
dispensaries. Most dramatically, NIDA's varieties contain only 27% of the THC
levels and as much as 11-23 times the Cannabinol (CBN) content compared to what
is available in the state-legal markets. Research restricted to using the current
range of federally-produced Cannabis thus may yield limited insights into the
chemical, biological and pharmacological properties, and medical potential of
material that is available in the state markets. Investigation is urgently needed
on the full diversity of Cannabis chemotypes known to be available to the public.
PMID- 28422146
TI - A study of the effects of synthesis conditions on Li5FeO4/carbon nanotube
composites.
AB - Li5FeO4/carbon nanotube (LFO/CNT) composites composed of sub-micron sized LFO and
a nanocarbon with high electrical conductivity were successfully synthesized for
the use as lithium ion predoping source in lithium ion cells. The phase of LFO in
the composite was found to be very sensitive to the synthesis conditions, such as
the heat treatment temperature, type of lithium salt, and physical state of the
precursors (powder or pellet), due to the carbothermic reduction of Fe3O4 by CNTs
during high temperature solid state reaction. Under optimized synthesis
conditions, LFO/CNT composites could be synthesized without the formation of
impurities. To the best of our knowledge, this is the first report on the
synthesis and characterization of a sub-micron sized LFO/CNT composites.
PMID- 28422147
TI - Construction of a high-density linkage map and fine mapping of QTLs for growth
and gonad related traits in blunt snout bream.
AB - High-density genetic maps based on SNPs are essential for fine mapping loci
controlling specific traits for fish species. Using restriction-site associated
DNA tag sequencing (RAD-Seq) technology, we identified 42,784 SNPs evenly
distributed across the Megalobrama amblycephala genome. Based on 2 parents and
187 intra-specific hybridization progenies, a total of 14,648 high-confidence
SNPs were assigned to 24 consensus linkage groups (LGs) of maternal and paternal
map. The total length of the integrated map was 3,258.38 cM with an average
distance of 0.57 cM among 5676 effective loci, thereby representing the first
high-density genetic map reported for M. amblycephala. A total of eight positive
quantitative trait loci (QTLs) were detected in QTL analysis. Of that, five QTL
explained >=35% of phenotypic variation for growth traits and three QTL explained
>=16% phenotypic variation for gonad related traits. A total of 176 mapped
markers had significant hits in the zebrafish genome and almost all of the 24
putative-chromosomes of M. amblycephala were in relatively conserved synteny with
chromosomes of zebrafish. Almost all M. amblycephala and zebrafish chromosomes
had a 1:1 correspondence except for putative-chromosome 4, which mapped to two
chromosomes of zebrafish caused by the difference in chromosome numbers between
two species.
PMID- 28422148
TI - Chemical and Bioactive Profiling, and Biological Activities of Coral Fungi from
Northwestern Himalayas.
AB - Ramaria Fr. and Clavaria L. are the two major genera of coral mushrooms within
families Gomphaceae and Clavariaceae, respectively. Besides having important role
in forest ecology, some species of these are reported to possess high
nutraceutical and bioactive potential. There is a hidden diversity of coral
mushrooms in Northwestern Himalayas. Present studies describe the detailed
biochemical profiling and antioxidant, and antibacterial activities of twelve
coral mushroom species. Biochemical profiling of nutrients and nutraceuticals was
done with standard techniques and by using HPLC, UPLC and GC. Experiments were
also conducted to check the toxic metals detection. Antioxidant activities were
calculated using EC50 values from mushroom extracts. Antibacterial activities
were checked on six pathogenic bacterial strains through minimum inhibition
concenterations. Although, differences were observed in the net values of
individual species but all the species were found to be rich in protein, macro
and micro minerals, carbohydrates, unsaturated fatty acids, essential amino
acids, phenolics, tocopherols, anthocynadins and carotenoids. All the species
showed significant antioxidant and antibacterial activities. These species are
reported to free from heavy toxic metals. Present studies will open the way for
their large scale commercial exploitations and use in pharmaceutical industries
as antioxidant, antibacterial and nutraceutical constituents.
PMID- 28422149
TI - Monitoring seasonal influenza epidemics by using internet search data with an
ensemble penalized regression model.
AB - Seasonal influenza epidemics cause serious public health problems in China.
Search queries-based surveillance was recently proposed to complement traditional
monitoring approaches of influenza epidemics. However, developing robust
techniques of search query selection and enhancing predictability for influenza
epidemics remains a challenge. This study aimed to develop a novel ensemble
framework to improve penalized regression models for detecting influenza
epidemics by using Baidu search engine query data from China. The ensemble
framework applied a combination of bootstrap aggregating (bagging) and rank
aggregation method to optimize penalized regression models. Different algorithms
including lasso, ridge, elastic net and the algorithms in the proposed ensemble
framework were compared by using Baidu search engine queries. Most of the
selected search terms captured the peaks and troughs of the time series curves of
influenza cases. The predictability of the conventional penalized regression
models were improved by the proposed ensemble framework. The elastic net
regression model outperformed the compared models, with the minimum prediction
errors. We established a Baidu search engine queries-based surveillance model for
monitoring influenza epidemics, and the proposed model provides a useful tool to
support the public health response to influenza and other infectious diseases.
PMID- 28422150
TI - Elucidation of crystal and electronic structures within highly strained BiFeO3 by
transmission electron microscopy and first-principles simulation.
AB - Crystal and electronic structures of ~380 nm BiFeO3 film grown on LaAlO3
substrate are comprehensively studied using advanced transmission electron
microscopy (TEM) technique combined with first-principles theory. Cross-sectional
TEM images reveal the BiFeO3 film consists of two zones with different crystal
structures. While zone II turns out to have rhombohedral BiFeO3, the crystal
structure of zone I matches none of BiFeO3 phases reported experimentally or
predicted theoretically. Detailed electron diffraction analysis combined with
first-principles calculation allows us to determine that zone I displays an
orthorhombic-like monoclinic structure with space group of Cm (=8). The growth
mechanism and electronic structure in zone I are further discussed in comparison
with those of zone II. This study is the first to provide an experimentally
validated complete crystallographic detail of a highly strained BiFeO3 that
includes the lattice parameter as well as the basis atom locations in the unit
cell.
PMID- 28422151
TI - Determinants of Thermostability in Serine Hydroxymethyltransferase Identified by
Principal Component Analysis.
AB - Protein thermostability has received growing attention in recent years. Little is
known about the determinants of thermal resistance in individual protein
families. However, it is known that the mechanism is family-dependent and not
identical for all proteins. We present a multivariate statistical analysis to
find the determinants of thermostability in one protein family, the serine
hydroxymethyltransferase family. Based on principal component analysis, we
identified three amino acid fragments as the potential determinants of
thermostability. The correlation coefficients between all the putative fragments
and the protein thermostability were significant according to multivariable
linear regression. Within the fragments, four critical amino acid positions were
identified, and they indicated the contributions of Leu, Val, Lys, Asp, Glu, and
Phe to thermostability. Moreover, we analyzed the insertions/deletions of amino
acids in the sequence, which showed that thermophilic SHMTs tend to insert or
delete residues in the C-terminal domain rather than the N-terminal domain. Our
study provided a promising approach to perform a preliminary search for the
determinants of thermophilic proteins. It could be extended to other protein
families to explore their own strategies for adapting to high temperature.
PMID- 28422152
TI - Towards automatic pulmonary nodule management in lung cancer screening with deep
learning.
AB - The introduction of lung cancer screening programs will produce an unprecedented
amount of chest CT scans in the near future, which radiologists will have to read
in order to decide on a patient follow-up strategy. According to the current
guidelines, the workup of screen-detected nodules strongly relies on nodule size
and nodule type. In this paper, we present a deep learning system based on multi
stream multi-scale convolutional networks, which automatically classifies all
nodule types relevant for nodule workup. The system processes raw CT data
containing a nodule without the need for any additional information such as
nodule segmentation or nodule size and learns a representation of 3D data by
analyzing an arbitrary number of 2D views of a given nodule. The deep learning
system was trained with data from the Italian MILD screening trial and validated
on an independent set of data from the Danish DLCST screening trial. We analyze
the advantage of processing nodules at multiple scales with a multi-stream
convolutional network architecture, and we show that the proposed deep learning
system achieves performance at classifying nodule type that surpasses the one of
classical machine learning approaches and is within the inter-observer
variability among four experienced human observers.
PMID- 28422153
TI - Clinical-pharmacogenetic models for personalized cancer treatment: application to
malignant mesothelioma.
AB - Large interindividual differences in treatment outcome are observed in cancer
patients undergoing chemotherapy. Our aim was to develop and validate clinical
pharmacogenetic prediction models of gemcitabine/cisplatin or
pemetrexed/cisplatin treatment outcome and develop an algorithm for genotype
based treatment recommendations in malignant mesothelioma (MM). We genotyped 189
MM patients for polymorphisms in gemcitabine, pemetrexed and cisplatin
metabolism, transport and drug target genes and DNA repair pathways. To build
respective clinical-pharmacogenetic models, pharmacogenetic scores were assigned
by rounding regression coefficients. Gemcitabine/cisplatin model was based on
training group of 71 patients and included CRP, histological type, performance
status, RRM1 rs1042927, ERCC2 rs13181, ERCC1 rs3212986, and XRCC1 rs25487.
Patients with higher score had shorter progression-free (PFS) and overall
survival (P < 0.001). This model's sensitivity was 0.615 and specificity 0.812.
In independent validation group of 66 patients the sensitivity and specificity
were 0.667 and 0.641, respectively. Pemetrexed/cisplatin model was based on 57
patients and included CRP, MTHFD1 rs2236225, and ABCC2 rs2273697. Patients with
higher score had worse response and shorter PFS (P < 0.001). This model's
sensitivity was 0.750 and specificity 0.607. In independent validation group of
20 patients the sensitivity and specificity were 0.889 and 0.500, respectively.
The proposed algorithm based on these models could enable the choice of the most
effective chemotherapy for 85.5% of patients and lead to improved treatment
outcome in MM.
PMID- 28422154
TI - Integration of liver gene co-expression networks and eGWAs analyses highlighted
candidate regulators implicated in lipid metabolism in pigs.
AB - In the present study, liver co-expression networks and expression Genome Wide
Association Study (eGWAS) were performed to identify DNA variants and molecular
pathways implicated in the functional regulatory mechanisms of meat quality
traits in pigs. With this purpose, the liver mRNA expression of 44 candidates
genes related with lipid metabolism was analysed in 111 Iberian x Landrace
backcross animals. The eGWAS identified 92 eSNPs located in seven chromosomal
regions and associated with eight genes: CROT, CYP2U1, DGAT1, EGF, FABP1, FABP5,
PLA2G12A, and PPARA. Remarkably, cis-eSNPs associated with FABP1 gene expression
which may be determining the C18:2(n-6)/C18:3(n-3) ratio in backfat through the
multiple interaction of DNA variants and genes were identified. Furthermore, a
hotspot on SSC8 associated with the gene expression of eight genes was identified
and the TBCK gene was pointed out as candidate gene regulating it. Our results
also suggested that the PI3K-Akt-mTOR pathway plays an important role in the
control of the analysed genes highlighting nuclear receptors as the NR3C1 or
PPARA. Finally, sex-dimorphism associated with hepatic lipid metabolism was
identified with over-representation of female-biased genes. These results
increase our knowledge of the genetic architecture underlying fat composition
traits.
PMID- 28422155
TI - In vitro biocompatibility study of sub-5 nm silica-coated magnetic iron oxide
fluorescent nanoparticles for potential biomedical application.
AB - Magnetic iron oxide nanoparticles (IONPs), for their intriguing properties, have
attracted a great interest as they can be employed in many different biomedical
applications. In this multidisciplinary study, we synthetized and characterized
ultrafine 3 nm superparamagnetic water-dispersible nanoparticles. By a facile and
inexpensive one-pot approach, nanoparticles were coated with a shell of silica
and contemporarily functionalized with fluorescein isothiocyanate (FITC) dye. The
obtained sub-5 nm silica-coated magnetic iron oxide fluorescent (sub-5 SIO-Fl)
nanoparticles were assayed for cellular uptake, biocompatibility and cytotoxicity
in a human colon cancer cellular model. By confocal microscopy analysis we
demonstrated that nanoparticles as-synthesized are internalized and do not
interfere with the CaCo-2 cell cytoskeletal organization nor with their cellular
adhesion. We assessed that they do not exhibit cytotoxicity, providing evidence
that they do not affect shape, proliferation, cellular viability, cell cycle
distribution and progression. We further demonstrated at molecular level that
these nanoparticles do not interfere with the expression of key differentiation
markers and do not affect pro-inflammatory cytokines response in Caco-2 cells.
Overall, these results showed the in vitro biocompatibility of the sub-5 SIO-Fl
nanoparticles promising their safe employ for diagnostic and therapeutic
biomedical applications.
PMID- 28422156
TI - Anticancer properties of a defensin like class IId bacteriocin Laterosporulin10.
AB - Laterosporulin10 (LS10) is a defensin like peptide from Brevibacillus sp. strain
SKDU10 that inhibited microbial pathogens. However, in this study, anticancer
activity of LS10 was examined against different cancer cell lines and compared
with normal cells. LS10 displayed cytotoxicity against cancer cells like MCF-7,
HEK293T, HT1080, HeLa and H1299 at below 10 MUM concentration, but not against
prostate epithelium cells RWPE-1. Additionally, no hemolysis was observed at
significantly higher concentration compared to IC50 values observed for different
cancer cell lines. Release of lactate dehydrogenase from cancer cell lines at 15
MUM concentration upon 120 min treatment indicated the lytic ability of LS10.
Accordingly, electron microscopy experiments also confirmed the necrotic effect
of LS10 at 15 MUM concentration against cancer cells. Furthermore, flow cytometry
analysis of treated cancer cell lines revealed that LS10 induce apoptosis even at
2.5 MUM concentration. Nevertheless, RWPE-1 cells remained viable even at 20 MUM
concentration. These results provide evidence that LS10 is an anticancer
bacteriocin, which causes apoptotic and necrotic death of cancer cells at lower
and higher concentrations, respectively. Taken all results together, the present
study signifies that LS10 is an anticancer peptide that could be further
developed for therapeutic applications.
PMID- 28422157
TI - Detection of a new pyrethroid resistance mutation (V410L) in the sodium channel
of Aedes aegypti: a potential challenge for mosquito control.
AB - The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is
the principal vector of dengue, yellow fever, Zika and Chikungunya viruses.
Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes,
despite the development of pyrethroid resistance in many mosquito populations
worldwide. Here, we report a Brazilian strain of A. aegypti with high levels
(approximately 100-60,000 fold) of resistance to both type I and type II
pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel
from this resistant strain. This study is the first report of the V410L mutation
in mosquitoes. Alone or in combination with the F1534C mutation, the V410L
mutation drastically reduced the sensitivity of mosquito sodium channels
expressed in Xenopus oocytes to both type I and type II pyrethroids. The V410L
mutation presents a serious challenge for the control of A. aegypti and will
compromise the use of pyrethroids for the control of A. aegypti in Brazil;
therefore, early monitoring of the frequency of the V410L mutation will be a key
resistance management strategy to preserve the effectiveness of pyrethroid
insecticides.
PMID- 28422158
TI - Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion
that is highly dependent upon oxidative stress.
AB - Isothiocyanates, such as phenethyl isothiocyanate (PEITC), are formed following
the consumption of cruciferous vegetables and generate reactive oxygen species
(ROS) that lead to the induction of cytoprotective genes such as the UDP
glucuronosyltransferases (UGTs). The induction of ROS activates the Nrf2-Keap 1
pathway leading to the induction of genes through antioxidant response elements
(AREs). UGT1A1, the sole enzyme responsible for the metabolism of bilirubin, can
be induced following activation of Nrf2. When neonatal humanized UGT1 (hUGT1)
mice, which exhibit severe levels of total serum bilirubin (TSB) because of a
developmental delay in expression of the UGT1A1 gene, were treated with PEITC,
TSB levels were reduced. Liver and intestinal UGT1A1 were induced, along with
murine CYP2B10, a consensus CAR target gene. In both neonatal and adult hUGT1/Car
/- mice, PEITC was unable to induce CYP2B10. A similar result was observed
following analysis of UGT1A1 expression in liver. However, TSB levels were still
reduced in hUGT1/Car-/- neonatal mice because of ROS induction of intestinal
UGT1A1. When oxidative stress was blocked by exposing mice to N-acetylcysteine,
induction of liver UGT1A1 and CYP2B10 by PEITC was prevented. Thus, new findings
in this report link an important role in CAR activation that is dependent upon
oxidative stress.
PMID- 28422159
TI - Spastic paraplegia-linked phospholipase PAPLA1 is necessary for development,
reproduction, and energy metabolism in Drosophila.
AB - The human PAPLA1 phospholipase family is associated with hereditary spastic
paraplegia (HSP), a neurodegenerative syndrome characterized by progressive
spasticity and weakness of the lower limbs. Taking advantage of a new Drosophila
PAPLA1 mutant, we describe here novel functions of this phospholipase family in
fly development, reproduction, and energy metabolism. Loss of Drosophila PAPLA1
reduces egg hatchability, pre-adult viability, developmental speed, and impairs
reproductive functions of both males and females. In addition, our work describes
novel metabolic roles of PAPLA1, manifested as decreased food intake, lower
energy expenditure, and reduced ATP levels of the mutants. Moreover, PAPLA1 has
an important role in the glycogen metabolism, being required for expression of
several regulators of carbohydrate metabolism and for glycogen storage. In
contrast, global loss of PAPLA1 does not affect fat reserves in adult flies.
Interestingly, several of the PAPLA1 phenotypes in fly are reminiscent of
symptoms described in some HSP patients, suggesting evolutionary conserved
functions of PAPLA1 family in the affected processes. Altogether, this work
reveals novel physiological functions of PAPLA1, which are likely evolutionary
conserved from flies to humans.
PMID- 28422160
TI - Efficient electrical control of thin-film black phosphorus bandgap.
AB - Recently rediscovered black phosphorus is a layered semiconductor with promising
electronic and photonic properties. Dynamic control of its bandgap can allow for
the exploration of new physical phenomena. However, theoretical investigations
and photoemission spectroscopy experiments indicate that in its few-layer form,
an exceedingly large electric field in the order of several volts per nanometre
is required to effectively tune its bandgap, making the direct electrical control
unfeasible. Here we reveal the unique thickness-dependent bandgap tuning
properties in intrinsic black phosphorus, arising from the strong interlayer
electronic-state coupling. Furthermore, leveraging a 10 nm-thick black
phosphorus, we continuously tune its bandgap from ~300 to below 50 meV, using a
moderate displacement field up to 1.1 V nm-1. Such dynamic tuning of bandgap may
not only extend the operational wavelength range of tunable black phosphorus
photonic devices, but also pave the way for the investigation of electrically
tunable topological insulators and semimetals.
PMID- 28422161
TI - Impact of low-temperature, overcast and rainy weather during the reproductive
growth stage on lodging resistance of rice.
AB - The objectives of this study were to explore the mechanism by which the lodging
resistance of the rice population during the late growth period responds to low
temperature, overcast and rainy weather during the reproductive growth stage.
Field experiments were conducted using indica rice Yliangyou2 (lodging-resistance
variety), IIyou084 (lodging-susceptible variety) and japonica rice Wuyunjing23
(lodging-resistance variety) and W3668 (lodging- susceptible variety) in 2013
(high temperature and strong radiation during the rice reproductive growth
stage), 2012 and 2014 (low temperature and weak radiation during rice
reproductive growth stage). The results showed that the length of the basal
internodes and the height of the gravitational centres were greater in plants
grown in 2014. Dry weight of basal culms, culm diameter, lignin content and total
content of structural carbohydrates (lignin and cellulose) in basal internodes
were reduced in these plants, causing a significant reduction in the bending
stress and lodging resistance of the rice stems. Low-temperature, overcast and
rainy weather had a greater effect on lodging resistance in indica rice compared
with japonica rice. This was reflected in a greater reduction in the lignin
content of the indica rice stems, which yielded a significantly lower breaking
strength and bending stress.
PMID- 28422162
TI - A comparative analysis of human and mouse islet G-protein coupled receptor
expression.
AB - G-protein coupled receptors (GPCRs) are essential for islet function, but most
studies use rodent islets due to limited human islet availability. We have
systematically compared the GPCR mRNA expression in human and mouse islets to
determine to what extent mouse islets can be used as surrogates for human islets
to study islet GPCR function, and we have identified species-specific expression
of several GPCRs. The A3 receptor (ADORA3) was expressed only in mouse islets and
the A3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse
islets, with no effect on human islets. Similarly, mRNAs encoding the galanin
receptors GAL1 (GALR1), GAL2 (GALR2) and GAL3 GALR3) were abundantly expressed in
mouse islets but present only at low levels in human islets, so that it reads
(GALR3) and galanin inhibited insulin secretion only from mouse islets.
Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its
selective activation by CH 275 inhibited insulin secretion from human islets,
with no effect on mouse islets. Our comprehensive human and mouse islet GPCR
atlas has demonstrated that species differences do exist in islet GPCR expression
and function, which are likely to impact on the translatability of mouse studies
to the human context.
PMID- 28422163
TI - Distorted Immunodominance by Linker Sequences or other Epitopes from a Second
Protein Antigen During Antigen-Processing.
AB - The immune system focuses on and responds to very few representative
immunodominant epitopes from pathogenic insults. However, due to the complexity
of the antigen processing, understanding the parameters that lead to
immunodominance has proved difficult. In an attempt to uncover the determinants
of immunodominance among several dominant epitopes, we utilized a cell free
antigen processing system and allowed the system to identify the hierarchies
among potential determinants. We then tested the results in vivo; in mice and in
human. We report here, that immunodominance of known sequences in a given protein
can change if two or more proteins are being processed and presented
simultaneously. Surprisingly, we find that new spacer/tag sequences commonly
added to proteins for purification purposes can distort the capture of the
physiological immunodominant epitopes. We warn against adding tags and spacers to
candidate vaccines, or recommend cleaving it off before using for vaccination.
PMID- 28422164
TI - On the Role of the Electrical Field in Spark Plasma Sintering of UO2+x.
AB - The electric field has a large effect on the stoichiometry and grain growth of
UO2+x during Spark Plasma Sintering. UO2+x is gradually reduced to UO2.00 as a
function of sintering temperature and time. A gradient in the oxidation state
within the pellets is observed in intermediate conditions. The shape of the
gradient depends unequivocally on the direction of the electrical field. The
positive surface of the pellet shows a higher oxidation state compared to the
negative one. An area with larger grain size is found close to the positive
electrode, but not in contact with it. We interpret these findings with the
redistribution of defects under an electric field, which affect the stoichiometry
of UO2+x and thus the cation diffusivity. The results bear implications for
understanding the electric field assisted sintering of UO2 and non-stoichiometric
oxides in general.
PMID- 28422165
TI - Structural basis of inhibition of lipid-linked oligosaccharide flippase PglK by a
conformational nanobody.
AB - PglK is an ABC transporter that flips a lipid-linked oligosaccharide (LLO) that
serves as a donor in protein N-glycosylation. Previous structures revealed two
inward-facing conformations, both with very large separations of the nucleotide
binding domains (NBDs), and a closed, ADP-bound state that featured an occluded
cavity. To investigate additional states, we developed conformation-sensitive,
single-domain camelid nanobodies (Nb) and studied their effect on PglK activity.
Biochemical, structural, and mass spectrometric analyses revealed that one
inhibitory Nb binds as a single copy to homodimeric PglK. The co-crystal
structure of this Nb and ADP-bound PglK revealed a new, narrowly inward-open
conformation. Rather than inducing asymmetry in the PglK homodimer, the binding
of one Nb results in steric constraints that prevent a second Nb to access the
symmetry-related site in PglK. The Nb performed its inhibitory role by a "sticky
doorstop" mechanism, where inhibition of ATP hydrolysis and LLO flipping activity
occurs due to impaired closing of the NBD interface, which prevents PglK from
converting to an outward-open conformation. This inhibitory mode suggests tight
conformational coupling between the ATPase sites, which may apply to other ABC
transporters.
PMID- 28422166
TI - Identification and characterization of miRNAs in two closely related C4 and C3
species of Cleome by high-throughput sequencing.
AB - Cleome gynandra and Cleome hassleriana, which are C4 and C3 plants, respectively,
are two species of Cleome. The close genetic relationship between C. gynandra and
C. hassleriana provides advantages for discovering the differences in leaf
development and physiological processes between C3 and C4 plants. MicroRNAs
(miRNAs) are a class of important regulators of various biological processes. In
this study, we investigate the differences in the characteristics of miRNAs
between C. gynandra and C. hassleriana using high-throughput sequencing
technology. In total, 94 and 102 known miRNAs were identified in C. gynandra and
C. hassleriana, respectively, of which 3 were specific for C. gynandra and 10
were specific for C. hassleriana. Ninety-one common miRNAs were identified in
both species. In addition, 4 novel miRNAs were detected, including three in C.
gynandra and three in C. hassleriana. Of these miRNAs, 67 were significantly
differentially expressed between these two species and were involved in extensive
biological processes, such as glycol-metabolism and photosynthesis. Our study not
only provided resources for C. gynandra and C. hassleriana research but also
provided useful clues for the understanding of the roles of miRNAs in the
alterations of biological processes in leaf tissues during the evolution of the
C4 pathway.
PMID- 28422167
TI - Biotin-transfer from a trifunctional crosslinker for identification of cell
surface receptors of soluble protein ligands.
AB - Here we describe a novel crosslinker and its application as a biotin-transfer
reagent to identify cell surface receptors of soluble protein ligands on live
cells. This crosslinker contains three functional groups: an aldehyde-reactive
aminooxy group, a sulfhydryl, and a biotin (ASB). It is readily synthesized via a
3-step addition reaction using standard solid-phase peptide synthesis methods and
commercially available intermediates, allowing access to laboratories without
specialized synthetic chemistry capabilities. For the biotin-transfer method, ASB
is linked to a protein ligand through the sulfhydryl group in a two-step process
that allows the introduction of a disulfide bond between the ligand and the
crosslinker. Incubation of the labelled ligand with oxidized live cells leads to
the formation of crosslinks with aldehyde-containing glycans on the cell surface
receptor. Subsequent reduction of the disulfide bond results in biotin transfer
from the ligand to the cell surface receptor. Protein biotinylation that is
mediated by ligand binding to its receptor is differentiated from background
biotinylation events by comparison with a similarly labelled control protein
using comparative proteomic mass spectrometry to quantify streptavidin-bound
proteins. Using this method, we successfully identified the cell surface
receptors of a peptide hormone, a monoclonal antibody, and a single-domain
antibody-Fc fusion construct.
PMID- 28422168
TI - Competitions between prosocial exclusions and punishments in finite populations.
AB - Prosocial punishment has been proved to be a powerful mean to promote
cooperation. Recent studies have found that social exclusion, which indeed can be
regarded as a kind of punishment, can also support cooperation. However, if
prosocial punishment and exclusion are both present, it is still unclear which
strategy is more advantageous to curb free-riders. Here we first study the direct
competition between different types of punishment and exclusion. We find that
pool (peer) exclusion can always outperform pool (peer) punishment both in the
optional and in the compulsory public goods game, no matter whether second-order
sanctioning is considered or not. Furthermore, peer exclusion does better than
pool exclusion both in the optional and in the compulsory game, but the situation
is reversed in the presence of second-order exclusion. Finally, we extend the
competition among all possible sanctioning strategies and find that peer
exclusion can outperform all other strategies in the absence of second-order
exclusion and punishment, while pool exclusion prevails when second-order
sanctioning is possible. Our results demonstrate that exclusion is a more
powerful strategy than punishment for the resolution of social dilemmas.
PMID- 28422169
TI - The role of domestication and experience in 'looking back' towards humans in an
unsolvable task.
AB - A key element thought to have changed during domestication is dogs' propensity to
communicate with humans, particularly their inclination to gaze at them. A
classic test to measure this is the 'unsolvable task', where after repeated
successes in obtaining a reward by object-manipulation, the animal is confronted
with an unsolvable version of the task. 'Looking back' at humans has been
considered an expression of dogs seeking help. While it occurs more in dogs than
in socialized wolves, the level of exposure to human communication also appears
to play a role. We tested similarly raised adult wolves and mixed breed dogs, pet
dogs and free-ranging dogs. Unlike previous studies, as well as species and
levels of socialization, we included 'persistence' in trying to solve the task as
a potential explanatory factor. Wolves were more persistent than all dog groups.
Regardless of socialization or species, less persistent animals looked back
sooner and longer. Free-ranging dogs, despite little exposure to dog-human
communication, behaved similarly to other dogs. Together, results suggest that
basic wolf-dog differences in motivation and exploration may override differences
in human-directed behaviour when animals are equally socialized, and that once
the human is considered a social partner, looking behaviour occurs easily.
PMID- 28422170
TI - Dynamic through-silicon-via filling process using copper electrochemical
deposition at different current densities.
AB - This work demonstrates the dynamic through-silicon-via (TSV) filling process
through staged electrodeposition experiments at different current densities.
Different morphologies corresponding to TSV filling results can be obtained by
controlling the applied current density. Specifically, a low current density (4
mA/cm2) induces seam defect filling, a medium current density (7 mA/cm2) induces
defect-free filling, and a high current density (10 mA/cm2) induces void defect
filling. Analysis of the filling coefficient indicates that the effect of current
density on the TSV filling models is triggered by the coupling effect of
consumption and diffusion of additives and copper ions. Further, the
morphological evolution of plating reveals that the local deposition rate is
affected by the geometrical characteristics of the plating.
PMID- 28422171
TI - Nanoporous Microsphere Assembly of Iodine-Functionalised Silver Nanoparticles as
a Novel Mini-Substrate for Enriching and Sensing.
AB - Herein, debris particulates of nanoporous silver (np-Ag) were synthesised by a
dealloying method, and their integration behaviour and surface-enhanced Raman
scattering (SERS) properties during iodine functionalisation were examined. It
was found that the dealloyed np-Ag debris particulates gradually assembled to
form rigid nanoporous microspheres comprising Ag nano-ligaments due to mechanical
collisions during iodine treatment. High-resolution transmission electron
microscopy and X-ray photoelectron microscopy clearly showed the iodide surface
of np-Ag, which was dotted with iodine or iodide 'nanoislands'. The exceptional,
and unexpected, integration and surface structures result in a highly enhanced
localised surface plasmon resonance. Furthermore, the robust nanoporous
microspheres can be employed individually as as-produced miniaturised electrodes
to electrically enrich target molecules at parts-per-trillion levels, so as to
achieve charge selectivity and superior detectability compared with the ordinary
SERS effect.
PMID- 28422172
TI - Transient elastography as a screening tool for liver fibrosis in a large
hemodialysis population.
AB - Metabolic syndrome, an etiological factor in non-alcoholic fatty liver disease
(NAFLD), is often present in hemodialysis patients. Little is known about the
prevalence of, and factors associated with, liver fibrosis in hemodialysis
populations. We used transient elastography (TE) to investigate these phenomena.
659 patients treated with chronic hemodialysis were enrolled. We excluded those
with excess alcohol intake, liver stiffness measurement (LSM) failure, or
unreliable LSM values. LSM >=8.0 kPa was used as a cutoff suggesting clinically
relevant fibrosis. Controlled attenuation parameter (CAP) >= 232.5 dB/m was used
as a cutoff suggesting steatosis. 333 patients (50.5%) had steatosis, 159 (24.1%)
had hepatitis B or C, and 149 (22.6%) had LSM >=8.0 kPa. In multivariable
analyses, male gender (OR: 2.16; 95% CI: 1.29-3.63; P = 0.004), overweight body
habitus (OR:2.31; 95% CI: 1.35-3.94; P = 0.002), high AST level (OR:1.08; 95% CI:
1.04-1.12; P < 0.001), low albumin level (OR: 0.25; 95% CI: 0.12-0.53; P <
0.001), low creatinine level (OR: 0.89; 95% CI: 0.79-1.00; P = 0.05) and low
platelet count (OR: 0.99; 95% CI: 0.99-1.00; P < 0.001) were associated with LSM
>=8.0 kPa. We thus conclude that hemodialysis patients have a high prevalence of
NAFLD and clinically relevant fibrosis. NAFLD may be an important determinant of
clinically relevant fibrosis in hemodialysis populations.
PMID- 28422173
TI - Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular
similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome.
AB - Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo
heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS
patients show multiple anomalies including intellectual disability, a distinctive
facial appearance, microcephaly, congenital heart defects and Hirschsprung
disease. However, the skin manifestation(s) of patients with MOWS has not been
documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers
Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic
scars and joint hypermobility. MOWS patients showed a thinner dermal thickness
and electron microscopy revealed miniaturized collagen fibrils. Notably, mice
with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated
redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to
those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a
decreased expression of extracellular matrix (ECM) molecules, such as collagens,
whereas molecules involved in degradation of the ECM, such as matrix
metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin
fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit
an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to
ZEB2 mutations or deletions.
PMID- 28422174
TI - High expression of matrix metalloproteinases 16 is associated with the aggressive
malignant behavior and poor survival outcome in colorectal carcinoma.
AB - Recent evidence suggested an important role of matrix metalloproteinases 16
(MMP16) in the progression of several cancers. However, the contribution of MMP16
to colorectal cancer (CRC) remains elusive. In this study, we combined analyzed
the MMP16 expression in The Cancer Genome Atlas (TCGA), GSE39582 database and in
house database. In TCGA and GSE39584 database, the log-rank test demonstrated
that overall survival (OS) for patients with low MMP16 expression in tumor
tissues was significantly higher than those with high expression (P < 0.05). In
the validation cohort, high MMP16 expression was significantly correlated with N
stage (P = 0.008) and lymphovascular invasion (P = 0.002). The 5-year OS and
disease free survival (DFS) in high and low MMP16 expression groups were 66.0%
and 80.6%, 54.3% and 72.8%, respectively. Univariate and multivariate analysis
showed that high MMP16 expression was an independently prognosis factor for both
OS and DFS (P < 0.05). Functional study found that silencing MMP16 expression
could inhibit migration and invasion of colon cancer cells. In conclusion, high
expression of MMP16 is associated with the aggressive malignant behavior and poor
survival outcome of CRC patients. MMP16 can serve as an indicator of prognosis as
well as a potential novel target for treatment of CRC patients.
PMID- 28422175
TI - Assessment of China's H5N1 routine vaccination strategy.
AB - In this study, a simulation model was used to assess the epidemiological and
economic impacts of the routine vaccination strategy for H5N1 in China at the
national level. The results of the simulation show that a routine vaccination
strategy at the national level could have a substantial impact on decreasing H5N1
outbreaks; it could therefore markedly reduce the severity and duration of an
H5N1 epidemic at the national level in China. Under a routine vaccination
programme, when a flock is infected, the number of depopulated birds could be
reduced by approximately 91%, the outbreak duration could be reduced by one
fourth, and the probability of an H5N1 outbreak could be reduced to 51.5%.
Although the use of vaccination has obvious benefits, if indirect costs were not
considered, the mean direct cost of simulated disease control without vaccination
was only 1.36% of the cost of the routine vaccination strategy, and this former
approach would have saved 57 billion yuan for all poultry in China from 2004 to
2012. Traditional H5N1 control strategies with culling programmes at the national
level represented a better choice for China.
PMID- 28422177
TI - Microbiota: Diet can protect against type 1 diabetes.
PMID- 28422176
TI - The characteristics of newly diagnosed adult early-onset diabetes: a population
based cross-sectional study.
AB - To investigate the characteristics of newly diagnosed early-onset diabetes in the
Chinese population, 2801 newly diagnosed diabetes participants without known
diabetes or pre-diabetes in a national cross-sectional survey were analysed.
Participants were divided into quartiles (22-43, 44-52, 53-61 and >61 years)
according to age of diabetes onset and the first group were defined as early
onset diabetes group. Early-onset diabetes group had lower systolic blood
pressure (SBP), total cholesterol, low density lipoprotein cholesterol, 2-hour
post prandial blood glucose and urine albumin creatinine ratio. There was no
difference in body mass index, Homeostasis model assessment (HOMA) of beta cell
function and diabetes family history between early-onset diabetes participants
and any other age groups. HOMA of insulin resistance (IR) scores and disposition
index 30 minutes after glucose load (DI30) were increased in early-onset diabetes
participants. The beta cell function declination was more deteriorated in early
onset diabetes participants. Male gender, triglycerides, HOMA-IR and DI30 were
positively associated with an earlier age at diagnosis. In conclusion, patients
diagnosed with diabetes at a younger age are characterized by a similar
cardiovascular risk profile with increased insulin resistance and more severe
beta cell failure than patients diagnosed at a later age.
PMID- 28422178
TI - Enhancing protective immunity to malaria with a highly immunogenic virus-like
particle vaccine.
AB - The leading malaria vaccine in development is the circumsporozoite protein (CSP)
based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of
Plasmodium falciparum infection. It induces modest levels of protective efficacy,
thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance
vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and
therefore developed a next-generation RTS,S-like vaccine, called R21. The major
improvement is that in contrast to RTS,S, R21 particles are formed from a single
CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a
vaccine composed of a much higher proportion of CSP than in RTS,S. We demonstrate
that in BALB/c mice R21 is immunogenic at very low doses and when administered
with the adjuvants Abisco-100 and Matrix-M it elicits sterile protection against
transgenic sporozoite challenge. Concurrent induction of potent cellular and
humoral immune responses was also achieved by combining R21 with TRAP-based viral
vectors and protective efficacy was significantly enhanced. In addition, in
contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was
induced. These studies identify an anti-sporozoite vaccine component that may
improve upon the current leading malaria vaccine RTS,S. R21 is now under
evaluation in Phase 1/2a clinical trials.
PMID- 28422179
TI - Heritability maps of human face morphology through large-scale automated three
dimensional phenotyping.
AB - The human face is a complex trait under strong genetic control, as evidenced by
the striking visual similarity between twins. Nevertheless, heritability
estimates of facial traits have often been surprisingly low or difficult to
replicate. Furthermore, the construction of facial phenotypes that correspond to
naturally perceived facial features remains largely a mystery. We present here a
large-scale heritability study of face geometry that aims to address these
issues. High-resolution, three-dimensional facial models have been acquired on a
cohort of 952 twins recruited from the TwinsUK registry, and processed through a
novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm).
The algorithm places thousands of landmarks throughout the facial surface and
automatically establishes point-wise correspondence across faces. These landmarks
enabled us to intuitively characterize facial geometry at a fine level of detail
through curvature measurements, yielding accurate heritability maps of the human
face (www.heritabilitymaps.info).
PMID- 28422180
TI - Patterning Graphene Film by Magnetic-assisted UV Ozonation.
AB - Developing an alternative method for fabricating microscale graphene patterns
that overcomes the obstacles of organic contamination, linewidth resolution, and
substrate damaging is paramount for applications in optoelectronics. Here we
propose to pattern chemical vapor deposition grown graphene film through a
stencil mask by magnetic-assisted ultraviolet (UV) ozonation under irradiation of
a xenon excimer lamp. In this process, the paramagnetic oxygen molecules and
photochemically generated oxygen radicals are magnetized and attracted in an
inhomogenous external magnetic field. As a consequence, their random motions
convert into directional, which can greatly modify or enhance the quality of
graphene patterns. Using a ferromagnetic steel mask, an approximately vertical
magnetic-field-assisted UV ozonation (BZ = 0.31 T, ?BZ = 90 T . m-1) has a
capability of patterning graphene microstructures with a line width of 29 MUm and
lateral under-oxidation less than 4 MUm. Our approach is applicable to patterning
graphene field-effect transistor arrays, and it can be a promising solution
toward resist-free, substrate non-damaging, and cost effective microscale
patterning of graphene film.
PMID- 28422181
TI - Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and
their major contributed antioxidant compounds.
AB - The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea
were evaluated, and their major antioxidant compounds contributed to the total
amount of synergy were determined. The antioxidant compounds in O. fragrans
flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The
synergistic antioxidant interactions between O. fragrans flowers with green tea
and their antioxidant compounds were tested using the Prieto's model after the
simulated digestion. The main antioxidant compounds in O. fragrans flowers were
acteoside and salideroside, whereas the main antioxidant compounds in green tea
were caffeine, gallic acid, and L-epicatechin. The significant synergistic effect
between O. fragrans flowers and green tea was observed and among nearly all of
the combinations of their antioxidant compounds. Among the combinations,
acteoside and gallic acid contributed most to the antioxidant synergy between O.
fragrans flowers and green tea. However, the simulated digestion decreased this
antioxidant synergy because it reduced the contents and the antioxidant
capacities of their compounds, as well as the antioxidant synergy among the
compounds.
PMID- 28422182
TI - Carbon nanotube/metal-sulfide composite flexible electrodes for high-performance
quantum dot-sensitized solar cells and supercapacitors.
AB - Carbon nanotubes (CNT) and metal sulfides have attracted considerable attention
owing to their outstanding properties and multiple application areas, such as
electrochemical energy conversion and energy storage. Here we describes a cost
effective and facile solution approach to the preparation of metal sulfides (PbS,
CuS, CoS, and NiS) grown directly on CNTs, such as CNT/PbS, CNT/CuS, CNT/CoS, and
CNT/NiS flexible electrodes for quantum dot-sensitized solar cells (QDSSCs) and
supercapacitors (SCs). X-ray photoelectron spectroscopy, X-ray diffraction, and
transmission electron microscopy confirmed that the CNT network was covered with
high-purity metal sulfide compounds. QDSSCs equipped with the CNT/NiS counter
electrode (CE) showed an impressive energy conversion efficiency (eta) of 6.41%
and remarkable stability. Interestingly, the assembled symmetric CNT/NiS-based
polysulfide SC device exhibited a maximal energy density of 35.39 W h kg-1 and
superior cycling durability with 98.39% retention after 1,000 cycles compared to
the other CNT/metal-sulfides. The elevated performance of the composites was
attributed mainly to the good conductivity, high surface area with mesoporous
structures and stability of the CNTs and the high electrocatalytic activity of
the metal sulfides. Overall, the designed composite CNT/metal-sulfide electrodes
offer an important guideline for the development of next level energy conversion
and energy storage devices.
PMID- 28422183
TI - Enhanced superconductivity accompanying a Lifshitz transition in electron-doped
FeSe monolayer.
AB - The origin of enhanced superconductivity over 50 K in the recently discovered
FeSe monolayer films grown on SrTiO3 (STO), as compared to 8 K in bulk FeSe, is
intensely debated. As with the ferrochalcogenides AxFe2-ySe2 and potassium-doped
FeSe, which also have a relatively high-superconducting critical temperature
(Tc), the Fermi surface (FS) of the FeSe/STO monolayer films is free of hole-like
FS, suggesting that a Lifshitz transition by which these hole FSs vanish may help
increasing Tc. However, the fundamental reasons explaining this increase of Tc
remain unclear. Here we report a 15 K jump of Tc accompanying a second Lifshitz
transition characterized by the emergence of an electron pocket at the Brillouin
zone centre, which is triggered by high-electron doping following in situ
deposition of potassium on FeSe/STO monolayer films. Our results suggest that the
pairing interactions are orbital dependent in generating enhanced
superconductivity in FeSe.
PMID- 28422184
TI - Sea-level proxies in Holocene raised beach ridge deposits (Greenland) revealed by
ground-penetrating radar.
AB - Identification of sea-level proxies is important for reconstruction of past sea
level variation. Methods for reconstructing Holocene relative sea-level curves
are crucial for quantification of the impact of Greenland ice thickness variation
on global sea level and vertical land movement. Arctic beach ridges constitute
important potential archives of sea-level variation. However, their surface
morphology may have undergone modification since deposition due to
freezing/thawing processes and erosion, and their morphology may therefore not be
trustworthy for sea-level reconstruction. Therefore, geophysical imaging is used
to examine the internal structures of the beach ridges and to define a sea-level
proxy unaffected by surface processes. The GPR reflections from study sites in
West and South Greenland show deposition of beachface deposits and upper
shoreface deposits; the contact between steeply dipping beachface reflections and
less-dipping shoreface reflections is used as sea-level proxy. Numerous points
are identified along GPR transects facilitating reconstruction of relative sea
level variation of hitherto unprecedented resolution. Erosional events and
deformation caused by freezing/thawing processes are clearly delineated. The
approach constitutes a solid base for reconstruction of relative sea-level curves
affected by a well-defined vertical land movement history since the studied beach
ridge systems represent long time intervals and only relatively small spatial
extents.
PMID- 28422185
TI - Improved ganoderic acids production in Ganoderma lucidum by wood decaying
components.
AB - Ganoderma lucidum is a legendary Traditional Chinese Medicine (TCM) over a few
thousands of years and one kind of its major active components are Ganoderic
acids (GAs). GAs are largely produced in the mushroom primordium and fruiting
body but much less in mycelium stage. However, little is known on the underlying
regulatory mechanism. As a saprophytic fungus, G. lucidum solely obtains
nutrients by wood decaying. Wood in general contains sophisticated chemical
components with diverse structural units. To explore a strategy that extensively
leads to GAs induction in the submerged liquid fermentation, all chemical
components that might be possibly from the wood decaying were tested individually
as GAs inducers. It was found that GAs production increased 85.96% by 1.5%
microcrystalline cellulose (MCC) and 63.90% by 0.5% D-galactose. The
transcription level of a few rate-limiting or chemically diverting enzymes
responsible for GAs biosynthesis was greatly induced by MCC and D-galactose. The
concentration and time-course titration study indicated that these two chemicals
might not be utilized as carbon sources but they played a comprehensive role in
the secondary metabolites synthesis. Our data indicated that MCC and D-galactose
might be further industrialized for higher GAs production in G. lucidum in
submerged fermentation.
PMID- 28422186
TI - High-fat diet induces systemic B-cell repertoire changes associated with insulin
resistance.
AB - The development of obesity-associated insulin resistance is associated with B
lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B
cell ablation. To characterize potentially pathogenic B-cell repertoires in this
disorder, we performed high-throughput immunoglobulin (Ig) sequencing from
multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD
significantly changed the biochemical properties of Ig heavy-chain
complementarity-determining region-3 (CDRH3) sequences, selecting for IgA
antibodies with shorter and more hydrophobic CDRH3 in multiple tissues. A set of
convergent antibodies of highly similar sequences found in the VAT of HFD mice
but not RD mice showed significant somatic mutation, suggesting a response shared
between mice to a common antigen or antigens. These findings indicate that a
simple high-fat dietary intervention has a major impact on mouse B-cell
repertoires, particularly in adipose tissues.
PMID- 28422187
TI - A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue
reactivation and hypersensitivity in the lung.
AB - Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell
rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification
for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1)
regulates key mechanisms underlying lymphoid tissue biology and its chemical
modulation causes lymphocyte retention in lymph nodes. Given the putative
immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated
whether or not chemical modulation of S1P1 caused lymphocyte retention within
TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically
to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity
pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by
S1P1-positive microvessels. Upon MSS rechallenge, the S1P1 agonist RP001
prevented the pulmonary increase of CXCL13, a chief regulator of B-cell
recruitment in lymphoid tissues. This was associated with a complete inhibition
of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS
specific antibody titers in the lung. Interference with TLT reactivation was
associated with a 77% reduction of neutrophil accumulation and with full
inhibition of protein-rich leakage in the airways. Thus, an S1P1 agonist hinders
TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic
features of experimental hypersensitivity pneumonitis.
PMID- 28422188
TI - Resolvin D1 enhances the resolution of lung inflammation caused by long-term
Pseudomonas aeruginosa infection.
AB - Pseudomonas aeruginosa lung infection is a main cause of disability and mortality
worldwide. Acute inflammation and its timely resolution are crucial for ensuring
bacterial clearance and limiting tissue damage. Here, we investigated protective
actions of resolvin (Rv) D1 in lung infection induced by the RP73 clinical strain
of P. aeruginosa. RvD1 significantly diminished bacterial growth and neutrophil
infiltration during acute pneumonia caused by RP73. Inoculum of RP73, immobilized
in agar beads, resulted in persistent lung infection up to 21 days, leading to a
non resolving inflammation reminiscent of human pathology. RvD1 significantly
reduced bacterial titer, leukocyte infiltration, and lung tissue damage. In
murine lung macrophages sorted during P. aeruginosa chronic infection, RvD1
regulated the expression of Toll-like receptors, downstream genes, and microRNA
(miR)-21 and 155, resulting in reduced inflammatory signaling. In vitro, RvD1
enhanced phagocytosis of P. aeruginosa by neutrophils and macrophages,
recapitulating its in vivo actions. These results unveil protective functions and
mechanisms of action of RvD1 in acute and chronic P. aeruginosa pneumonia,
providing evidence for its potent pro-resolution and tissue protective properties
on airway mucosal tissue during infection.
PMID- 28422189
TI - Exome Analysis of Rare and Common Variants within the NOD Signaling Pathway.
AB - Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder.
This study looks at the burden of common and rare coding mutations within 41
genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106
control samples underwent whole-exome sequencing. We compared the burden of
common, rare and private mutation between these two groups using the SKAT-O test.
An independent replication cohort of 33 cases and 111 controls was used to
validate significant findings. We observed variation in 40 of 41 genes comprising
the NOD signaling pathway. Four genes were significantly associated with disease
in the discovery cohort (BIRC2 p = 0.004, NFKB1 p = 0.005, NOD2 p = 0.029 and
SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041)
and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on
the combined discovery and replication cohort confirmed association for BIRC2 (p
= 0.030). We successfully applied burden of mutation testing that jointly
assesses common and rare variants, identifying two previously implicated genes
(NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously
unreported gene (BIRC2). The identification of this novel gene provides a wider
role for the inhibitor of apoptosis gene family in IBD pathogenesis.
PMID- 28422190
TI - Current carried by the Slc26 family member prestin does not flow through the
transporter pathway.
AB - Prestin in the lateral membrane of outer hair cells, is responsible for
electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's
voltage sensitivity is influenced by intracellular chloride. A regulator of
intracellular chloride is a stretch-sensitive, non-selective conductance within
the lateral membrane, GmetL. We determine that prestin itself possesses a stretch
sensitive, non-selective conductance that is largest in the presence of
thiocyanate ions. This conductance is independent of the anion transporter
mechanism. Prestin has been modeled, based on structural data from related anion
transporters (SLC26Dg and UraA), to have a 7 + 7 inverted repeat structure with
anion transport initiated by chloride binding at the intracellular cleft.
Mutation of residues that bind intracellular chloride, and salicylate treatment
which prevents chloride binding, have no effect on thiocyanate conductance. In
contrast, other mutations reduce the conductance while preserving NLC. When
superimposed on prestin's structure, the location of these mutations indicates
that the ion permeation pathway lies between the core and gate ring of helices,
distinct from the transporter pathway. The uncoupled current is reminiscent of an
omega current in voltage-gated ion channels. We suggest that prestin itself is
the main regulator of intracellular chloride concentration via a route distinct
from its transporter pathway.
PMID- 28422191
TI - Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification
and treatment.
AB - Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic
malignancies in which blasts show markers of multiple developmental lineages and
cannot be clearly classified as acute myeloid or lymphoblastic leukemias.
Historically, various names and classifications were used for this rare entity
accounting for 2-5% of all acute leukemias depending on the diagnostic criterias
used. The currently valid classification of myeloid neoplasms and acute leukemia
published by the World Health Organization (WHO) in 2016 refers to this group of
diseases as MPAL. Because adverse cytogenetic abnormalities are frequently
present, MPAL is generally considered a disease with a poor prognosis. Knowledge
of its treatment is limited to retrospective analyses of small patient cohorts.
So far, no treatment recommendations verified by prospective studies have been
published. The reported data suggest that induction therapy for acute
lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation
is more effective than induction therapy for acute myeloid leukemia or
consolidation chemotherapy. The establishment of cooperative groups and
international registries based on the recent WHO criterias are required to ensure
further progress in understanding and treatment of MPAL. This review summarizes
current knowledge on the diagnosis, classification, prognosis and treatment of
MPAL patients.
PMID- 28422192
TI - Polymorphisms at 1q32, 8q24, and 17q22 loci are associated with nonsyndromic
cleft lip with or without cleft palate risk in the Slovak population.
AB - BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is the
most common orofacial birth defect with an aetiology involving both genetic and
environmental factors. Genome-wide association studies (GWAS) have identified
several genomic susceptibility regions for nsCL/P. In the present study, the
three well established single nucleotide polymorphisms (SNPs) identified by GWAS
(rs987525 at 8q24, rs7078160 at 10q25, and rs227731 at 17q22 loci) and one SNP
identified by candidate gene study (rs642961 in IRF6 gene at 1q32 locus) were
analysed for an association with nsCL/P in Slovak population. METHODS: Nucleotide
variants were genotyped in 165 nsCL/P patients and 326 unaffected controls. All
variants of interest were genotyped using high-resolution melting analysis after
real-time PCR. RESULTS: We found significant differences between patient and
control groups with respect to the allele and genotype frequencies for the SNPs
at the 1q32, 8q24, and 17q22 loci. SNP at the 10q25 locus showed a trend toward
association with nsCL/P risk. CONCLUSIONS: The results suggest that SNPs at the
1q32, 8q24 and 17q22 loci may contribute to the nsCL/P risk in Slovak population.
PMID- 28422193
TI - Challenges in developing direct carbon fuel cells.
AB - A direct carbon fuel cell (DCFC) can produce electricity with both superior
electrical efficiency and fuel utilisation compared to all other types of fuel
cells. Although the first DCFC prototype was proposed in 1896, there was, until
the 1970s, little sustained effort to investigate further, because of technology
development issues. Interest in DCFCs has recently been reinvigorated as a
possible method of replacing conventional coal-fired power plants to meet the
demands for lower CO2 emissions, and indeed for efficient utilisation of waste
derived chars. In this article, recent developments in direct carbon conversion
are reviewed, with the principal emphasis on the materials involved. The
development of electrolytes, anodes and cathodes as well as fuel sources is
examined. The activity and chemical stability of the anode materials are a
critical concern addressed in the development of new materials. Redox media of
molten carbonate or molten metal facilitating the transportation of ions offer
promising possibilities for carbon oxidation. The suitability of different carbon
fuels in various DCFC systems, in terms of crystal structure, surface properties,
impurities and particle size, is also discussed. We explore the influence of a
variety of parameters on the electrochemical performance of DCFCs, with regard to
their open circuit voltage, power output and lifetime. The challenges faced in
developing DCFCs are summarised, and potential prospects of the system are
outlined.
PMID- 28422194
TI - Field induced anomalous spreading, oscillation, ejection, spinning, and breaking
of oil droplets on a strongly slipping water surface.
AB - Application of an electric field on an oil droplet floating on the surface of a
deionized water bath showed interesting motions such as spreading, oscillation,
and ejection. The electric field was generated by connecting a pointed platinum
cathode at the top of the oil droplet and a copper anode coated with polymer at
the bottom of the water layer. The experimental setup mimicked a conventional
electrowetting setup with the exception that the oil was spread on a soft and
deformable water isolator. While at relatively lower field intensities we
observed spreading of the droplet, at intermediate field intensities the droplet
oscillated around the platinum cathode, before ejecting out at a speed as high as
~5 body lengths per second at even stronger field intensities. The experiments
suggested that when the electric field was ramped up abruptly to a particular
voltage, any of the spreading, oscillation, or ejection motions of the droplet
could be engendered at lower, intermediate and higher field intensities,
respectively. However, when the field was ramped up progressively by increasing
by a definite amount of voltage per unit time, all three aforementioned motions
could be generated simultaneously with the increase in the field intensity.
Interestingly, when the aforementioned setup was placed on a magnet, the droplet
showed a rotational motion under the influence of the Lorentz force, which was
generated because of the coupling of the weak leakage current with the externally
applied magnetic field. The spreading, oscillation, ejection, and rotation of the
droplet were found to be functions of the oil-water interfacial tension,
viscosity, and size of the oil droplet. We developed simple theoretical models to
explain the experimental results obtained. Importantly, rotating at a higher
speed broke the droplet into a number of smaller ones, owing to the combined
influence of the spreading due to the centripetal force and the shear at the oil
water interface. While the oscillatory and rotational motions of the
incompressible droplet could be employed as stirrers or impellers inside
microfluidic devices for mixing applications, the droplet ejection could be
employed for futuristic applications such as payload transport or drug delivery.
PMID- 28422195
TI - Inducible epitope imprinting: 'generating' the required binding site in membrane
receptors for targeted drug delivery.
AB - We report an inducible epitope imprinting strategy that as a template, a flexible
peptide chain can have a disordered-to-ordered conformational change by suitable
inducement through a molecular imprinting procedure, and the formed nanoparticles
can, in turn, remold the original peptide into the expected conformation and
specifically bind to the corresponding protein.
PMID- 28422196
TI - Boundary layer friction of solvate ionic liquids as a function of potential.
AB - Atomic force microscopy (AFM) has been used to investigate the potential
dependent boundary layer friction at solvate ionic liquid (SIL)-highly ordered
pyrolytic graphite (HOPG) and SIL-Au(111) interfaces. Friction trace and retrace
loops of lithium tetraglyme bis(trifluoromethylsulfonyl)amide (Li(G4) TFSI) at
HOPG present clearer stick-slip events at negative potentials than at positive
potentials, indicating that a Li+ cation layer adsorbed to the HOPG lattice at
negative potentials which enhances stick-slip events. The boundary layer friction
data for Li(G4) TFSI shows that at HOPG, friction forces at all potentials are
low. The TFSI- anion rich boundary layer at positive potentials is more
lubricating than the Li+ cation rich boundary layer at negative potentials. These
results suggest that boundary layers at all potentials are smooth and energy is
predominantly dissipated via stick-slip events. In contrast, friction at Au(111)
for Li(G4) TFSI is significantly higher at positive potentials than at negative
potentials, which is comparable to that at HOPG at the same potential. The
similarity of boundary layer friction at negatively charged HOPG and Au(111)
surfaces indicates that the boundary layer compositions are similar and rich in
Li+ cations for both surfaces at negative potentials. However, at Au(111), the
TFSI- rich boundary layer is less lubricating than the Li+ rich boundary layer,
which implies that anion reorientations rather than stick-slip events are the
predominant energy dissipation pathways. This is confirmed by the boundary
friction of Li(G4) NO3 at Au(111), which shows similar friction to Li(G4) TFSI at
negative potentials due to the same cation rich boundary layer composition, but
even higher friction at positive potentials, due to higher energy dissipation in
the NO3- rich boundary layer.
PMID- 28422197
TI - Coupling graphene nanomechanical motion to a single-electron transistor.
AB - Graphene-based electromechanical resonators have attracted great interest
recently because of the outstanding mechanical and electrical properties of
graphene and their various applications. However, the coupling between mechanical
motion and charge transport has not been explored in graphene. Herein, we studied
the mechanical properties of a suspended 50 nm wide graphene nanoribbon, which
also acts as a single-electron transistor (SET) at low temperatures. Using the
SET as a sensitive detector, we found that the resonance frequency could be tuned
from 82 MHz to 100 MHz and the quality factor exceeded 30 000. The strong charge
mechanical coupling was demonstrated by observing the SET induced ~140 kHz
resonance frequency shifts and mechanical damping. We also found that the SET can
enhance the nonlinearity of the resonator. Our SET-coupled graphene mechanical
resonator could approach an ultra-sensitive mass resolution of ~0.55 * 10-21 g
and a force sensitivity of ~1.9 * 10-19 N (Hz)-1/2, and can be further improved.
These properties indicate that our device is a good platform for both fundamental
physical studies and potential applications.
PMID- 28422198
TI - Multiplexed gene silencing in living cells and in vivo using a DNAzymes-CoOOH
nanocomposite.
AB - We demonstrate a novel DNAzymes-based nanocomposite that can simultaneously
silence three types of genes in living cells and in vivo. The synergetic strategy
for silencing three different genes can significantly enhance the knockdown
efficacy and effectively inhibit the cancer cells' progression.
PMID- 28422199
TI - Hybridization chain reactions on silica coated Qbeads for the colorimetric
detection of multiplex microRNAs.
AB - A robust Qbead platform that integrated with target-binding, hybridization chain
reaction and staining was developed for the direct multiplexed detection of
endogenous miRNAs by amplified Qbead-colour change.
PMID- 28422200
TI - Enhancing MRI of liver metastases with a zwitterionized biodegradable dendritic
contrast agent.
AB - Metastasis is the main reason for cancer-associated mortality, and accurate
diagnostic imaging of metastases is critical for the clinical administration and
tailoring personalized treatments for metastatic tumors. However, magnetic
resonance imaging of metastases in the liver is impeded by its low sensitivity
because the currently used contrast agents accumulate in hepatocytes and Kupffer
cells instead of cancer cells. Herein, a 4th generation zwitterionized
biodegradable dendritic contrast agent (DCA) with a size of ca. 9 nm and a
longitudinal relaxivity of 15.7 mM-1 s-1 in terms of Gd was synthesized and used
to enhance the MRI of liver metastasis. The DCA could remarkably enhance the MRI
of metastasized tumors in the liver, because it could simultaneously reduce the
background signal in the liver by avoiding uptake by hepatocytes and Kupffer
cells through the zwitterionization and increase the signal in tumors through the
enhanced permeability and retention effect. Moreover, in contrast to non
biodegradable DCA, this DCA showed minimal long-term Gd3+ retention in all organs
and tissues because it could be degraded into small fragments. The significant
capability of enhancing the MRI of metastases in the liver plus its excellent
biodegradability made this DCA a promising CA for metastatic tumor imaging.
PMID- 28422201
TI - Self-exothermic reaction prompted synthesis of single-layered graphene quantum
dots at room temperature.
AB - The easy fabrication of single-layered graphene quantum dots (s-GQDs) still faces
challenge. Herein, we report an efficient route to fabricate s-GQDs within 5 min
at room temperature by introducing a simple self-exothermic reaction. The as
prepared s-GQDs can specifically bind with aluminium ions to produce an
aggregation-induced emission enhancement effect.
PMID- 28422202
TI - Efficient phosphine-mediated formal C(sp3)-C(sp3) coupling reactions of alkyl
halides in batch and flow.
AB - The construction of C(sp3)-C(sp3) bond is an essential chemical transformation in
synthetic chemistry due to its abundance in organic scaffolds. Here we
demonstrate a valuable adaptation of the Wittig-type chemical procedure to
efficiently facilitate C(sp3)-C(sp3) bond formation utilizing a range of alkyl
building blocks. Additionally the method is amenable with flow synthesis to
afford coupled products in good to excellent yields without laborious
purification process.
PMID- 28422203
TI - A nanoporous Ag(i) coordination polymer for selective adsorption of carcinogenic
dye Acid Red 26.
AB - A cationic Ag(i) coordination polymer with 1D nanoporous channels (ca. 1.22 nm
diameter) shows the selective and complete removal of carcinogenic dye Acid Red
26 from aqueous solution upon the size-exclusion and charge-matching effect.
PMID- 28422204
TI - Interface modulation of bacteriogenic Ag/AgCl nanoparticles by boosting the
catalytic activity for reduction reactions using Co2+ ions.
AB - Boosting the low catalytic activity of bacteriogenic Ag/AgCl nanoparticles (NPs)
by adding Co2+ in a model reaction, i.e. p-nitrophenol (PNP) reduction, was
observed. Under optimal conditions, Co-Ag/AgCl NPs show an apparent rate constant
(kapp) of 0.0837 s-1 upon PNP reduction. Considering the trace amount of Co
Ag/AgCl NPs used in catalysis (about 1.2 MUg), the activity parameter kappa
(which is the ratio of kapp and catalyst mass) can reach more than 6.97 * 104 s-1
g-1, which is 214-fold higher than that of pristine Ag/AgCl NPs. Meanwhile, this
kappa value is also the highest value reported to date. In addition, the biogenic
Co-Ag/AgCl NPs exhibit superior catalytic activities over other substrates, such
as m-nitrophenol, o-nitrophenol, methyl orange and rhodamine B. The activity
enhancement mechanism is supposed to be that Co2+ acts as a Lewis acid, and
coordinates with the surface peptides to affect the electric field distribution
at the Ag/AgCl NP interface.
PMID- 28422205
TI - A general strategy for the in situ decoration of porous Mn-Co bi-metal oxides on
metal mesh/foam for high performance de-NOx monolith catalysts.
AB - Owing to their advantages of strong mechanical stability, plasticity, thermal
conductivity and mass transfer ability, metal foam or meshes are considered
promising monolith supports for de-NOx application. In this work, we developed a
facile method for the decoration of porous Mn-Co bi-metal oxides on Fe meshes.
The block-like structure was derived from in situ coating, and simultaneous
nucleation and growth of the Mn-Co hydroxide precursor, while the porous Mn-Co
oxides were formed via the calcination process. Moreover, the decoration of the
high-purity Co2MnO4 spinel could lead to enhanced reducibility and adsorption
behaviors, which are crucial to the catalytic process. Of note is the fact that
the Fe mesh used in the synthesis procedure could be substituted by various metal
supports including Ti mesh, Cu foam and Ni foam. Driven by the above motivations,
metal supports decorated with Mn-Co oxides were evaluated as monolith de-NOx
catalysts for the first time. Inspiringly, these catalysts demonstrate
outstanding low-temperature catalytic activity, desirable stability and excellent
H2O resistance. This work might open up a new path for the design and development
of high performance de-NOx monolith catalysts.
PMID- 28422206
TI - Cage-like B39+ clusters with the bonding pattern of sigma + pi double
delocalization: new members of the borospherene family.
AB - The recently observed cage-like borospherenes D2d B40-/0 and C3/C2 B39- have
attracted considerable attention in chemistry and materials science. Based on
extensive global minimum searches and first-principles theory calculations, we
present herein the possibility of cage-like Cs B39+ (1) and Cs B39+ (2) which
possess five hexagonal and heptagonal faces and one filled hexagon and follow the
bonding pattern of sigma + pi double delocalization with 12 delocalized pi bonds
over a sigma-skeleton, adding two new members to the borospherene family. IR,
Raman, and UV-vis spectra of Cs B39+ (1) and Cs B39+ (2) are computationally
simulated to facilitate their experimental characterization.
PMID- 28422207
TI - Oxygen thermomigration in acceptor-doped perovskite.
AB - The recent proposal of possible oxygen-thermomigration as a plausible mechanism
for unipolar resistive switching of oxide memristors is now widely employed in
modelling or simulating their memristive function on the grounds of the
conventional picture that the mobile component O is always thermophobic, with its
reduced heat-of-transport being equal to its migrational enthalpy (qO* = DeltaHm
> 0). At 1000 degrees C, we measured the thermomigration of mobile-component O
in a prototype memristive perovskite, CaTi0.90Sc0.10O2.95+delta, across its near
stoichiometric regime (delta ~ 0), where oxygen vacancy concentration is
essentially fixed by doping acceptor impurities (i.e., ). It has been found that
the reduced heat-of-transport of mobile O (qO*) varies systematically in the
range of -2 < qO*/eV <= +2, as the composition varies from hypo-(delta < 0) to
hyper-stoichiometry (delta > 0), exhibiting a sign reversal or thermomigration
direction change from thermophilic (qO* < 0) to thermophobic (qO* > 0). This sign
reversal is attributed to the change in the electronic ambipolar company of from
electrons to holes crossing the stoichiometric composition delta = 0. The
numerical data for qO* together with the measurement details are reported.
PMID- 28422208
TI - Encapsulation into complex coacervate core micelles promotes EGFP dimerization.
AB - Complex coacervate core micelles (C3Ms) are colloidal structures useful for
encapsulation of biomacromolecules. We previously demonstrated that enhanced
green fluorescent protein (EGFP) can be encapsulated into C3Ms using the diblock
copolymer poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205. This
packaging resulted in deviating spectroscopic features of the encapsulated EGFP
molecules. Here we show that for monomeric EGFP variant (mEGFP) micellar
encapsulation affects the absorption and fluorescence properties to a much lesser
extent, and that changes in circular dichroism characteristics are specific for
encapsulated EGFP. Time-resolved fluorescence anisotropy of encapsulated (m)EGFP
established the occurrence of homo-FRET (Forster resonance energy transfer) with
larger transfer correlation times in the case of EGFP. Together, these findings
support that EGFP dimerizes whereas the mEGFP mainly remains as a monomer in the
densely packed C3Ms. We propose that dimerization of encapsulated EGFP causes a
reorientation of Glu222, resulting in a pKa shift of the chromophore, which is
fully reversible after release of EGFP from the C3Ms at a high ionic strength.
PMID- 28422209
TI - Engineering the strongly correlated properties of bulk Ruddlesden-Popper
transition metal oxides via self-doping.
AB - We demonstrate via first-principles calculations a novel method of tuning the
electron-electron interactions in bulk oxide materials via controlling the
cationic layer arrangement. Using the Ruddlesden-Popper oxides LaSrMnO4 and
LaSrTiO4 as examples, our study demonstrates that a self-doping effect can be
induced by changing the stacking of the neutral and charged cationic layers. It
is believed that such a phenomenon is associated with different movements of
apical oxygen atoms, resulting in diverse bandgaps, magnetism and orbital degrees
of freedom in the same stoichiometric strongly-correlated material. This finding
may open up a new direction to engineer the transition metal oxides for practical
applications requiring tunable electronic properties without external doping.
PMID- 28422212
TI - Trends and challenges for microporous polymers.
AB - Microporous polymers are covalently bound, entirely organic materials which
possess very high surface areas. These materials have been intensively studied
within recent years and various interesting properties and possible applications
have been discovered and described. This review article starts with the question,
what makes microporous polymers special and are there certain features which
differentiate them from other microporous materials? Indeed, there are some
special structural and functional features found in microporous polymers which
make them really unique and merit further exploration. We focus here on
microporous polymers which are solution-processable, can be produced as thin
films on electrodes by oxidative polymerizations, are pi-conjugated organic
semiconductors, or which provide the possibility to introduce and exploit
distinct functional groups in an otherwise non-functional highly porous
environment. Emerging applications for these microporous polymers which make
explicit use of these unique features are further presented.
PMID- 28422213
TI - Revisiting the Julia-Colonna enantioselective epoxidation: supramolecular
catalysis in water.
AB - We describe an efficient epoxidation process leading to chiral epoxyketones using
the reusable homo-oligopeptide poly-l-leucine (PLL) in pure water, without any
organic co-solvent. A range of substituted epoxyketones can be accessed with good
conversions and high enantioselectivities. Based on the experimental results and
computational studies, we propose a mechanism that demonstrates the importance of
both the alpha-helical structure and the presence of a hydrophobic groove of the
homo-oligopeptide catalyst for reactivity and selectivity.
PMID- 28422214
TI - (Diisopropylammonium)2MnBr4: a multifunctional ferroelectric with efficient green
emission and excellent gas sensing properties.
AB - Combination of excellent optical properties and ferroelectricity of hybrid
materials leads to high-performance optoelectronic devices. Here we present a new
organic-inorganic hybrid compound (diisopropylammonium)2MnBr4 (DIPA2MnBr4) which
shows high temperature ferroelectricity accompanied by highly efficient green
light emission. DIPA2MnBr4 also exhibits sensitive and selective optical response
to alcohol vapors.
PMID- 28422216
TI - Design and preparation of efficient hydroisomerization catalysts by the formation
of stable SAPO-11 molecular sieve nanosheets with 10-20 nm thickness and
partially blocked acidic sites.
AB - SAPO-11 nanosheets with partially filled micropores (N-SAPO-11) and a thickness
of 10-20 nm were synthesized using polyhexamethylene biguanide hydrochloride
(PHMB) as a mesoporogen and di-n-propylamine (DPA) as a microporous template.
After Pt loading (0.5 wt%), the Pt/N-SAPO-11 catalyst exhibits higher selectivity
for the isomers and lower selectivity for cracking products than conventional
Pt/SAPO-11 catalysts in the hydroisomerization of n-dodecane.
PMID- 28422217
TI - Increased substrate affinity in the Escherichia coli L28R dihydrofolate reductase
mutant causes trimethoprim resistance.
AB - Dihydrofolate reductase (DHFR) is a ubiquitous enzyme with an essential role in
cell metabolism. DHFR catalyzes the reduction of dihydrofolate to
tetrahydrofolate, which is a precursor for purine and thymidylate synthesis.
Several DHFR targeting antifolate drugs including trimethoprim, a competitive
antibacterial inhibitor, have therefore been developed and are clinically used.
Evolution of resistance against antifolates is a common public health problem
rendering these drugs ineffective. To combat the resistance problem, it is
important to understand resistance-conferring changes in the DHFR structure and
accordingly develop alternative strategies. Here, we structurally and dynamically
characterize Escherichia coli DHFR in its wild type (WT) and trimethoprim
resistant L28R mutant forms in the presence of the substrate and its inhibitor
trimethoprim. We use molecular dynamics simulations to determine the
conformational space, loop dynamics and hydrogen bond distributions at the active
site of DHFR for the WT and the L28R mutant. We also report their experimental
kcat, Km, and Ki values, accompanied by isothermal titration calorimetry
measurements of DHFR that distinguish enthalpic and entropic contributions to
trimethoprim binding. Although mutations that confer resistance to competitive
inhibitors typically make enzymes more promiscuous and decrease affinity to both
the substrate and the inhibitor, strikingly, we find that the L28R mutant has a
unique resistance mechanism. While the binding affinity differences between the
WT and the mutant for the inhibitor and the substrate are small, the newly formed
extra hydrogen bonds with the aminobenzoyl glutamate tail of DHF in the L28R
mutant leads to increased barriers for the dissociation of the substrate and the
product. Therefore, the L28R mutant indirectly gains resistance by enjoying
prolonged binding times in the enzyme-substrate complex. While this also leads to
slower product release and decreases the catalytic rate of the L28R mutant, the
overall effect is the maintenance of a sufficient product formation rate.
Finally, the experimental and computational analyses together reveal the changes
that occur in the energetic landscape of DHFR upon the resistance-conferring L28R
mutation. We show that the negative entropy associated with the binding of
trimethoprim in WT DHFR is due to water organization at the binding interface.
Our study lays the framework to study structural changes in other trimethoprim
resistant DHFR mutants.
PMID- 28422218
TI - The nanostructure of a lithium glyme solvate ionic liquid at electrified
interfaces.
AB - Solvate ionic liquids are a subclass of ionic liquids that have the potential to
be used in a range of electrochemical devices. We present molecular dynamics
simulations of the interfacial structure of thin films of one such lithium based
solvate ionic liquid, [Li(G4)][TFSI], an equimolar solution of tetraglyme and
lithium bistriflimide. This solvate ionic liquid is shown to form a novel
interfacial structure at a plane electrode, which differs in a number of ways
from the nanostructure observed for a conventional ionic liquid at similar
interfaces. This paper explores the structural composition of the interfacial
layers of this solvate ionic liquid, including their variation with surface
charge, and the relation between chemical structure and interfacial arrangement.
PMID- 28422219
TI - A nematic to nematic transformation exhibited by a rod-like liquid crystal.
AB - A novel, highly polar rod-like liquid crystal was found to exhibit two distinct
nematic mesophases (N and NX). When studied by microscopy and X-ray scattering
experiments, and under applied electric fields, the nematic phases are
practically identical. However, calorimetry experiments refute the possibility of
an intervening smectic mesophase, and the transformation between the nematic
phases was associated with a weak thermal event. Analysis of measured dielectric
data, along with molecular properties obtained from DFT calculations, applying
the Maier-Meier relationship allowed for the degree of antiparallel pairing of
dipoles in both nematic phases to be quantified. Based on the results, we
conclude that the onset of the lower temperature phase is driven by the formation
of antiparallel molecular associations.
PMID- 28422221
TI - Designing new catalysts for synthetic fuels: general discussion.
PMID- 28422222
TI - Electron transfer in silicon-bridged adjacent chromophores: the source for blue
green emission.
AB - Si-Bridged chromophores have been proposed as sources for blue-green emission in
several technological applications. The origin of this dual emission is to be
found in an internal charge transfer reaction. The current work is an attempt to
describe the details of these processes in these kinds of substances, and to
design a molecular architecture to improve their performance. Nuclear motions
essential for intramolecular charge transfer (ICT) can involve processes from
twisted internal moieties to dielectric relaxation of the solvent. To address
these issues, we studied ICT between adjacent chromophores in a molecular
compound containing N-isopropylcarbazole (CBL) and 1,4-divinylbenzene (DVB)
linked by a dimethylsilylene bridge. In nonpolar solvents emission arises from
the local excited state (LE) of carbazole whereas in solvents of higher polarity
dual emission was detected (LE + ICT). The CT character of the additional
emission band was concluded from the linear dependence of the fluorescence maxima
on solvent polarity. Electron transfer from CBL to DVB resulted in a large
excited-state dipole moment (37.3 D) as determined from a solvatochromic plot and
DFT calculations. Steady-state and picosecond time-resolved fluorescence
experiments in butyronitrile (293-173 K) showed that the ICT excited state arises
from the LE state of carbazole. These results were analyzed and found to be in
accordance with an adiabatic version of Marcus theory including solvent
relaxation.
PMID- 28422225
TI - Layer-independent and layer-dependent nonlinear optical properties of two
dimensional GaX (X = S, Se, Te) nanosheets.
AB - Recently researchers have found that the non-resonant second-harmonic generation
(SHG) intensity of the GaSe monolayer (ML) is the strongest among all two
dimensional (2D) atomic layered crystals. Here we perform a systematic first
principles study of the SHG coefficient of GaX (X = S, Se, Te) monolayers (MLs)
and few-layers. We find that the non-resonant SHG intensity of the GaS ML can be
comparable with that of the GaSe ML, while the non-resonant SHG intensity of the
GaTe ML is much stronger than that of the GaSe ML. Furthermore, the magnitudes of
SHG coefficients of the few-layers exfoliated from bulk epsilon-GaSe and newly
constructed N1-GaSe crystals are very close to that of the GaSe ML, showing no
dependence on the layer number. The magnitude of the SHG coefficient of the
trilayer exfoliated from the bulk beta-GaSe crystals is around 1/3 of that of the
GaSe ML, decreasing rapidly with the layer number. This study indicates that a
strong SHG response can be obtained in a wide range of monolayers and few-layers.
Moreover, we point out that one can identify the layer number and the stacking
sequence of 2D nanosheets by measuring their elastic constants and SHG
coefficients.
PMID- 28422226
TI - Insights into water-mediated ion clustering in aqueous CaSO4 solutions: pre
nucleation cluster characteristics studied by ab initio calculations and
molecular dynamics simulations.
AB - The molecular structure of growth units building crystals is a fundamental issue
in the crystallization processes from aqueous solutions. In this work, a
systematic investigation of pre-nucleation clusters and their hydration
characteristics in aqueous CaSO4 solutions was performed using ab initio
calculations and molecular dynamics (MD) simulations. The results of ab initio
calculations and MD simulations indicate that the dominant species in aqueous
CaSO4 solutions are monodentate ion-associated structures. Compared with charged
ion clusters, neutral clusters are more likely to be present in an aqueous CaSO4
solution. Neutral (CaSO4)m clusters are probably the growth units involved in the
pre-nucleation or crystallization processes. Meanwhile, hydration behavior around
ion associated species in aqueous CaSO4 solutions plays an important role in
related phase/polymorphism selections. Upon ion clustering, the residence of some
water molecules around Ca2+ in ion-associated species is weakened while that of
some bridging waters is enhanced due to dual interaction by Ca2+ and SO42-. Some
phase/polymorphism selections can be achieved in aqueous CaSO4 solutions by
controlling the hydration around pre-nucleation clusters. Moreover, the
association trend between calcium and sulfate is found to be relatively strong,
which hints at the low solubility of calcium sulfate in water.
PMID- 28422229
TI - Dendritic growth of monolayer ternary WS2(1-x)Se2x flakes for enhanced hydrogen
evolution reaction.
AB - Two-dimensional transition-metal dichalcogenides (TMDs) have attracted much
research interest in the hydrogen evolution reaction (HER) due to their superior
electrocatalytic properties. Beyond binary TMDs, ternary TMD alloys, as
electrocatalysts, were also gradually acknowledged for their remarkable
efficiency in HER. Herein, we successfully synthesized monolayer dendritic
ternary WS2(1-x)Se2x flakes possessing abundant active edge sites on a single
crystalline SrTiO3 (STO(100)). And the obtained dendritic WS2(1-x)Se2x flakes
could be transferred intact to arbitrary substrates, for example, SiO2/Si and Au
foils. Intriguingly, the transferred dendritic WS2(1-x)Se2x flakes on Au foil
demonstrate a significant HER performance, reflected by a rather lower Tafel
slope of ~69 mV dec-1 and a much higher exchange current density of ~50.1 MUA cm
2 outshining other CVD-grown two-dimensional TMD flakes. Furthermore, our new
material shows excellent stability in electro-catalyzing the HER, suggestive of
its robustness for being an excellent electrocatalyst. We believe that this work
broadens the outlook for the synthesis of two-dimensional TMDs toward satisfying
the applications in electrocatalysis.
PMID- 28422232
TI - Editorial of the PCCP themed issue on "Physical Chemistry for Life Sciences".
PMID- 28422233
TI - Detection of stiff nanoparticles within cellular structures by contact resonance
atomic force microscopy subsurface nanomechanical imaging.
AB - Detecting stiff nanoparticles buried in soft biological matrices by atomic force
microscopy (AFM) based techniques represents a new frontier in the field of
scanning probe microscopies, originally developed as surface characterization
methods. Here we report the detection of stiff (magnetic) nanoparticles (NPs)
internalized in cells by using contact resonance AFM (CR-AFM) employed as a
potentially non-destructive subsurface characterization tool. Magnetite (Fe3O4)
NPs were internalized in microglial cells from cerebral cortices of mouse embryos
of 18 days by phagocytosis. Nanomechanical imaging of cells was performed by
detecting the contact resonance frequencies (CRFs) of an AFM cantilever held in
contact with the sample. Agglomerates of NPs internalized in cells were
visualized on the basis of the local increase in the contact stiffness with
respect to the surrounding biological matrix. A second AFM-based technique for
nanomechanical imaging, i.e., HarmoniXTM, as well as magnetic force microscopy
and light microscopy were used to confirm the CR-AFM results. Thus, CR-AFM was
demonstrated as a promising technique for subsurface imaging of nanomaterials in
biological samples.
PMID- 28422235
TI - A facile mechanochemical route to a covalently bonded graphitic carbon nitride (g
C3N4) and fullerene hybrid toward enhanced visible light photocatalytic hydrogen
production.
AB - Graphitic carbon nitride (g-C3N4) as an emerging two-dimensional (2D)
nanomaterial has been commonly used as a metal-free photocatalyst with potential
applications in visible light photocatalytic water-splitting. However, the
photocatalytic activity of g-C3N4 is quite low due to its relatively large band
gap and the existence of contact resistance between the nanosheets. Herein we
report for the first time the facile synthesis of a covalently bonded g-C3N4/C60
hybrid via a solid-state mechanochemical route and its application in
photocatalytic hydrogen production under visible light. The g-C3N4/C60 hybrid was
synthesized by ball-milling g-C3N4 and C60 in the presence of lithium hydroxide
(LiOH) as a catalyst. The hybrid nature and conformation of the g-C3N4/C60 hybrid
were confirmed by a series of spectroscopic and morphological studies, featuring
the covalent bonding of C60 onto the edges of g-C3N4 nanosheets via a four
membered ring of azetidine, which has never been reported in fullerene chemistry.
The g-C3N4/C60 hybrid was further applied to metal-free visible light
photocatalytic hydrogen production, affording a H2 production rate of 266 MUmol h
1 g-1 without using any noble metal cocatalyst such as Pt, which is about 4.0
times higher than that obtained for the pristine g-C3N4 photocatalyst.
PMID- 28422239
TI - Electro-osmosis at surfactant-laden liquid-gas interfaces: beyond standard
models.
AB - Electro-osmosis (EO) is a powerful tool to manipulate liquids in micro and
nanofluidic systems. While EO has been studied extensively at liquid-solid
interfaces, the case of liquid-vapor interfaces, found e.g. in foam films and
bubbles, remains to be explored. Here we perform molecular dynamics (MD)
simulations of EO in a film of aqueous electrolyte covered with fluid layers of
ionic surfactants and surrounded by gas. Following the experimental procedure, we
compute the zeta potential from the EO velocity, defined as the velocity
difference between the middle of the liquid film and the surrounding gas. We show
that the zeta potential can be smaller or larger than existing predictions
depending on the surfactant coverage. We explain the failure of previous
descriptions by the fact that surfactants and bound ions move as rigid bodies and
do not transmit the electric driving force to the liquid locally. Considering the
reciprocal streaming current effect, we then develop an extended model, which can
be used to predict the experimental zeta potential of surfactant-laden liquid-gas
interfaces.
PMID- 28422238
TI - 3D single-molecule tracking enables direct hybridization kinetics measurement in
solution.
AB - Single-molecule measurements of DNA hybridization kinetics are mostly performed
on a surface or inside a trap. Here we demonstrate a time-resolved, 3D single
molecule tracking (3D-SMT) method that allows us to follow a freely diffusing
ssDNA molecule in solution for hundreds of milliseconds or even seconds and
observe multiple annealing and melting events taking place on the same molecule.
This is achieved by combining confocal-feedback 3D-SMT with time-domain
fluorescence lifetime measurement, where fluorescence lifetime serves as the
indicator of hybridization. With sub-diffraction-limit spatial resolution in
molecular tracking and 15 ms temporal resolution in monitoring the change of
reporter's lifetime, we have demonstrated a full characterization of annealing
rate (kon = 5.13 * 106 M-1 s-1), melting rate (koff = 9.55 s-1), and association
constant (Ka = 0.54 MUM-1) of an 8 bp duplex model system diffusing at 4.8 MUm2 s
1. As our method completely eliminates the photobleaching artifacts and diffusion
interference, our kon and koff results well represent the real kinetics in
solution. Our binding kinetics measurement can be carried out in a low signal-to
noise ratio condition (SNR ~ 1.4) where ~130 recorded photons are sufficient for
a lifetime estimation. Using a population-level analysis, we can characterize
hybridization kinetics over a wide range (0.5-125 s-1), even beyond the
reciprocals of the lifetime monitoring temporal resolution and the average track
duration.
PMID- 28422240
TI - Zwitterionic pyrrolidene-phosphonates: inhibitors of the glycoside hydrolase-like
phosphorylase Streptomyces coelicolor GlgEI-V279S.
AB - We synthesized and evaluated new zwitterionic inhibitors against glycoside
hydrolase-like phosphorylase Streptomyces coelicolor (Sco) GlgEI-V279S which
plays a role in alpha-glucan biosynthesis. Sco GlgEI-V279S serves as a model
enzyme for validated anti-tuberculosis (TB) target Mycobacterium tuberculosis
(Mtb) GlgE. Pyrrolidine inhibitors 5 and 6 were designed based on transition
state considerations and incorporate a phosphonate on the pyrrolidine moiety to
expand the interaction network between the inhibitor and the enzyme active site.
Compounds 5 and 6 inhibited Sco GlgEI-V279S with Ki = 45 +/- 4 MUM and 95 +/- 16
MUM, respectively, and crystal structures of Sco GlgE-V279S-5 and Sco GlgE-V279S
6 were obtained at a 3.2 A and 2.5 A resolution, respectively.
PMID- 28422241
TI - Super-tough, ultra-stretchable and strongly compressive hydrogels with core-shell
latex particles inducing efficient aggregation of hydrophobic chains.
AB - Toughness, strechability and compressibility for hydrogels were ordinarily
balanced for their use as mechanically responsive materials. For example,
macromolecular microsphere composite hydrogels with chemical crosslinking
exhibited excellent compression strength and strechability, but poor tensile
stress. Here, a novel strategy for the preparation of a super-tough, ultra
stretchable and strongly compressive hydrogel was proposed by introducing core
shell latex particles (LPs) as crosslinking centers for inducing efficient
aggregation of hydrophobic chains. The core-shell LPs always maintained a
spherical shape due to the presence of a hard core even by an external force and
the soft shell could interact with hydrophobic chains due to hydrophobic
interactions. As a result, the hydrogels reinforced by core-shell LPs exhibited
not only a high tensile strength of 1.8 MPa and dramatic elongation of over 20
times, but also an excellent compressive performance of 13.5 MPa at a strain of
90%. The Mullins effect was verified for the validity of core-shell LP-reinforced
hydrogels by inducing aggregation of hydrophobic chains. The novel strategy
strives to provide a better avenue for designing and developing a new generation
of hydrophobic association tough hydrogels with excellent mechanical properties.
PMID- 28422244
TI - Adhesion and friction in polymer films on solid substrates: conformal sites
analysis and corresponding surface measurements.
AB - In this work, we present a statistical mechanical analysis to elucidate the
molecular-level factors responsible for the static and dynamic properties of
polymer films. This analysis, which we term conformal sites theory, establishes
that three dimensionless parameters play important roles in determining
differences from bulk behavior for thin polymer films near to surfaces: a
microscopic wetting parameter, alphawx, defined as the ratio of polymer-substrate
interaction to polymer-polymer interaction; a dimensionless film thickness, H*;
and dimensionless temperature, T*. The parameter alphawx introduced here provides
a more fundamental measure of wetting than previous metrics, since it is defined
in terms of intermolecular forces and the atomic structure of the substrate, and
so is valid at the nanoscale for gas, liquid or solid films. To test this
theoretical analysis, we also report atomic force microscopy measurements of the
friction coefficient (MU), adhesion force (FA) and glass transition temperature
(Tg) for thin films of two polymers, poly(methyl methacrylate) (PMMA) and
polystyrene (PS), on two planar substrates, graphite and silica. Both the
friction coefficient and the glass transition temperature are found to increase
as the film thickness decreases, and this increase is more pronounced for the
graphite than for the silica surface. The adhesion force is also greater for the
graphite surface. The larger effects encountered for the graphite surface are
attributed to the fact that the microscopic wetting parameter, alphawx, is larger
for graphite than for silica, indicating stronger attraction of polymer chains to
the graphite surface.
PMID- 28422248
TI - Umpolung of protons from H2O: a metal-free chemoselective reduction of carbonyl
compounds via B2pin2/H2O systems.
AB - H2O is routinely described as a proton donor, however, in the presence of diboron
compounds, the umpolung reaction of H2O under metal-free conditions was
successfully developed, which could afford hydride species, leading to a highly
efficient and chemoselective reduction of C[double bond, length as m-dash]O
bonds. This strategy exhibits excellent chemoselectivities toward carbonyl groups
in the presence of ester, olefin, halogen, thioether, sulfonyl, cyano as well as
heteroaromatic groups.
PMID- 28422249
TI - Disulfide bond formation of thiols by using carbon nanotubes.
AB - Clarification of the interactions between carbon nanotubes (CNTs) and
proteinogenic amino acids is a key approach to understanding CNT-protein
interactions. Previous studies have addressed the mechanism of the physical
adsorption of amino acids onto CNTs. However, little is known about their
chemical reactions in aqueous solutions. Here, we established dispersant-free
systems to clarify intrinsic CNT-thiol interactions. We demonstrated that the
redox reaction of CNTs with cysteine, containing a thiol group, leads to
disulfide bond formation between cysteine molecules, even under acidic
conditions. The generality of the redox reaction is validated using other thiols
such as dithiothreitol and glutathione. The present results suggest that
structures of proteins and peptides containing free thiol groups are chemically
modified and misfolded on CNT surfaces by this disulfide bond formation in
biological systems.
PMID- 28422250
TI - A novel nanomissile targeting two biomarkers and accurately bombing CTCs with
doxorubicin.
AB - Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer
survivors to develop deadly metastasis at 3-5 years after surgery; the current
chemotherapies can do nothing about these cells. Herein, we synthesized a novel
doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently
conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the
typical surface biomarkers of colorectal CTCs. The nanomissile can specifically
capture the metastasis-prone CTCs spiked in healthy human blood in a competitive
binding manner. The binding not only accurately delivers DOX into the cancer
cells via the biomarker-mediated endocytosis to inhibit CTC viability through the
DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the
endothelium and the consequent transmembrane migration through the DOX
independent mechanism. The molecular entity of the conjugate and its
pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via
various physiochemical characterizations including gel electrophoresis, which
proves the >8-hour biostability of the nanomissile in blood, long enough for it
to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis
more potently than its single aptamer-conjugated counterparts and DOX itself. The
present strategy may pave a new avenue for safe and effective cancer metastasis
chemoprevention.
PMID- 28422251
TI - "Anti-Michael addition" of Grignard reagents to sulfonylacetylenes: synthesis of
alkynes.
AB - In this work, the addition of Grignard reagents to arylsulfonylacetylenes, which
undergoes an "anti-Michael addition", resulting in their alkynylation under very
mild conditions is described. The simplicity of the experimental procedure and
the functional group tolerance are the main features of this methodology. This is
an important advantage over the use of organolithium at -78 degrees C that we
previously reported. Moreover, the synthesis of diynes and other examples showing
functional group tolerance in this anti-Michael reaction is also presented.
PMID- 28422253
TI - 3D-printed poly(vinylidene fluoride)/carbon nanotube composites as a tunable, low
cost chemical vapour sensing platform.
AB - We report the production of flexible, highly-conductive poly(vinylidene fluoride)
(PVDF) and multi-walled carbon nanotube (MWCNT) composites as filament feedstock
for 3D printing. This account further describes, for the first time, fused
deposition modelling (FDM) derived 3D-printed objects with chemiresistive
properties in response to volatile organic compounds. The typically prohibitive
thermal expansion and die swell characteristics of PVDF were minimized by the
presence of MWCNTs in the composites enabling straightforward processing and
printing. The nanotubes form a dispersed network as characterized by helium ion
microscopy, contributing to excellent conductivity (~3 * 10-2 S cm-1). The
printed composites contain little residual metal particulate relative to parts
from commercial PLA-nanocomposite material visualized by micro-X-ray computed
tomography (MU-CT) and corroborated with thermogravimetric analysis. Printed
sensing strips, with MWCNT loadings up to 15% mass, function as reversible vapour
sensors with the strongest responses arising with organic compounds capable of
readily intercalating and subsequently swelling the PVDF matrix (acetone and
ethyl acetate). A direct correlation between MWCNT concentration and resistance
change was also observed, with larger responses (up to 161% after 3 minutes)
being generated with decreased MWCNT loadings. These findings highlight the
utility of FDM printing in generating low-cost sensors that respond strongly and
reproducibly to target vapours. Furthermore, the sensors can be easily printed in
different geometries, expanding their utility to wearable form factors. The
proposed formulation strategy may be tailored to sense diverse sets of vapour
classes through structural modification of the polymer backbone and/or
functionalization of the nanotubes within the composite.
PMID- 28422254
TI - A dual enzyme-inorganic hybrid nanoflower incorporated microfluidic paper-based
analytic device (MUPAD) biosensor for sensitive visualized detection of glucose.
AB - A novel microfluidic paper-based analytic device (MUPAD) biosensor is developed
for sensitive and visualized detection of glucose. This biosensor is easily
fabricated using the wax printing technique, with a hybrid nanocomplex composed
of dual enzymes glucose oxidase (GOx) and horseradish peroxidase (HRP) and
Cu3(PO4)2 inorganic nanocrystals incorporated in the detection zones. The hybrid
nanocomplex is found to exhibit a flower-like structure, which allows co
immobilization of these two enzymes in a biocompatible environment. These
nanoflowers not only preserve the activity and enhance the stability of the
enzymes, but also facilitate the transport of the substrates between the two
enzymes. The biosensor is demonstrated to enable rapid and sensitive
quantification of glucose in the concentration range of 0.1-10 mM with a limit of
detection (LOD) of 25 MUM. It is also shown to be applicable to colorimetric
quantitative detection of glucose in human serum and whole blood samples,
implying its potential for clinical applications.
PMID- 28422258
TI - Catalyst-free synthesis of novel dimeric beta-carboline derivatives via an
unexpected [2 + 2 + 2] annulation.
AB - We report here an unexpected catalyst-free [2 + 2 + 2] annulation reaction which
allows access to novel complex dimeric beta-carboline derivatives in a single
step. Various substituted ynones could react with dihydro-beta-carboline imines
to deliver interesting [2 + 2 + 2] annulation products in moderate to good
yields. Alkynoates can also be tolerated in this system.
PMID- 28422260
TI - Measuring the porosity and compressibility of liquid-suspended porous particles
using ultrasound.
AB - A key parameter describing the behavior of suspensions is the volume fraction phi
of the solid particles that are dispersed in the liquid. Obtaining accurate
values for phi becomes difficult for porous particles, because they can absorb
some of the liquid. A prime example are the widely used cornstarch suspensions,
for which phi usually is only estimated from the mass fraction of particles. Here
we present a method to measure the effective porosity and compressibility of
porous particles with ultrasound. We obtain the speed of sound in dilute
cornstarch suspensions at multiple particle concentrations and with different
solvent compressibilities. With the measured particle porosity of 0.31 we are
able to calculate the volume fraction of the saturated particles reliably.
PMID- 28422262
TI - Rifamorpholines A-E, potential antibiotics from locust-associated actinobacteria
Amycolatopsis sp. Hca4.
AB - Cultivation of locust associated rare actinobacteria, Amycolatopsis sp. HCa4, has
provided five unusual macrolactams rifamorpholines A-E. Their structures were
determined by interpretation of spectroscopic and crystallographic data.
Rifamorpholines A-E possess an unprecedented 5/6/6/6 ring chromophore,
representing a new subclass of rifamycin antibiotics. The biosynthetic pathway
for compounds 1-5 involves a key 1,6-cyclization for the formation of the
morpholine ring. Compounds 2 and 4 showed potent activities against methicillin
resistant Staphylococcus aureus (MRSA) with MICs of 4.0 and 8.0 MUM,
respectively.
PMID- 28422263
TI - Synthesis of oxazolidinones: rhodium-catalyzed C-H amination of N
mesyloxycarbamates.
AB - N-Mesyloxycarbamates undergo intramolecular C-H amination reactions to afford
oxazolidinones in good to excellent yields in the presence of rhodium(ii)
carboxylate catalysts. The reaction is performed under green conditions and
potassium carbonate is used, forming biodegradable potassium mesylate as a
reaction by-product. This method enables the production of electron-rich,
electron-deficient, aromatic and heteroaromatic oxazolidinones in good to
excellent yields. Conformationally restricted cyclic secondary N
mesyloxycarbamates furnish cis-oxazolidinones in high yields and selectivity; DFT
calculations are provided to account for the observed selectivity. trans
Oxazolidinones were prepared from acyclic secondary N-mesyloxycarbamates using
Rh2(oct)4. The selectivity was reverted with a cytoxazone N-mesyloxycarbamate
precursor using large chiral rhodium(ii) carboxylate complexes, affording the
corresponding cis-oxazolidinone. This orthogonal selectivity was used to achieve
the formal synthesis of (-)-cytoxazone.
PMID- 28422264
TI - Rhodium-catalyzed addition of sulfonyl hydrazides to allenes: regioselective
synthesis of branched allylic sulfones.
AB - A rhodium-catalyzed regioselective addition of sulfonyl hydrazides to allenes is
reported. With Rh(i)/DPEphos/benzoic acid as the catalyst system, branched
allylic sulfones can be obtained, in good to excellent yields and
regioselectivities.
PMID- 28422265
TI - Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of
a tunable molecular bottlebrush scaffold.
AB - The ability to widely tune the design of macromolecular bottlebrushes provides
access to self-assembled nanostructures formed by microphase segregation in melt,
thin film and solution that depart from structures adopted by simple linear
copolymers. A series of random bottlebrush copolymers containing poly(3
hexylthiophene) (P3HT) and poly(d,l-lactide) (PLA) side chains grafted on a
poly(norbornene) backbone were synthesized via ring-opening metathesis
polymerization (ROMP) using the grafting through approach. P3HT side chains
induce a physical aggregation of the bottlebrush copolymers upon solvent removal
by vacuum drying, primarily driven by attractive pi-pi interactions; however, the
amount of aggregation can be controlled by adjusting side chain composition or by
adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular
dynamics simulations reveal that linear P3HT chains preferentially associate with
P3HT side chains of bottlebrush copolymers, which tends to reduce the
aggregation. The nanoscale morphology of microphase segregated thin films created
by casting P3HT-PLA random bottlebrush copolymers is highly dependent on the
composition of P3HT and PLA side chains, while domain spacing of nanostructures
is mainly determined by the length of the side chains. The selective removal of
PLA side chains under alkaline conditions generates nanoporous P3HT structures
that can be tuned by manipulating molecular design of the bottlebrush scaffold,
which is affected by molecular weight and grafting density of the side chains,
and their sequence. The ability to exploit the unusual architecture of
bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a
useful way to design templates for optoelectronic applications or membranes for
separations.
PMID- 28422266
TI - Transient Elastography May Improve Detection of Liver Fibrosis in Psoriasis
Patients Treated with Methotrexate.
PMID- 28422267
TI - Cycling in Canada.
AB - This article provides an overview of cycling, including fatalities and bicycle
helmet use, based on data from the 1994/1995 National Population Health Survey,
the 2013/2014 Canadian Community Health Survey and the Vital Statistics-Death
Database. In 2013/2014, an estimated 7.0 million Canadians aged 12 or older (24%)
reported cycling in the previous three months, compared with 6.5 million (29%) in
1994/95. The prevalence of cycling declined with age, and was more common among
males and people living in higher-income and -education households. From 1994
through 2012, 1,408 cyclists were killed, an average of 74 annually, most of whom
were male (84%). In 2013/2014, 45% of those who had cycled in the past three
months reported that they always wore a helmet.
PMID- 28422268
TI - Housing conditions and respiratory hospitalizations among First Nations people in
Canada.
AB - BACKGROUND: Respiratory diseases are among the leading causes of acute care
hospitalization for First Nations people. Poor housing conditions are associated
with respiratory disorders and may be related to the likelihood of
hospitalization. This analysis examines whether First Nations identity is
associated with higher odds of hospitalization for respiratory conditions
relative to non-Aboriginal persons, and whether such differences in
hospitalization rates remain after consideration of housing conditions. DATA AND
METHODS: Data from the 2006 Census linked to the Discharge Abstract Database were
used to analyze differences in hospitalization for respiratory tract infections
and asthma between First Nations and non-Aboriginal people when housing
conditions were taken into account. RESULTS: Rural on-reserve First Nations
people were more likely than non-Aboriginal people to be hospitalized for a
respiratory tract infection (1.5% versus 0.5%) or for asthma (0.2% versus 0.1%).
For respiratory tract infection hospitalizations, adjustment for housing
conditions, household income and residential location reduced differences, but
the odds remained nearly three times higher for on-reserve First Nations people
(OR = 2.83; CI: 2.69 to 2.99) and two times higher for off-reserve First Nations
people (OR = 2.03; CI: 1.87 to 2.21), compared with the non-Aboriginal cohort.
For asthma hospitalizations, adjustment for household income reduced the odds
more than did adjustment for housing conditions. Even with full adjustment, the
odds of asthma hospitalization relative to non-Aboriginal people remained
significantly higher for First Nations people. INTERPRETATION: First Nations
people are significantly more likely than non-Aboriginal people to be
hospitalized for respiratory tract infections and asthma, even when housing
conditions, household income and residential location are taken into account.
While housing conditions are associated with such hospitalizations, household
income may be more important.
PMID- 28422269
TI - Wake and light therapy for moderate-to-severe depression - a randomized
controlled trial.
AB - OBJECTIVE: To examine the efficacy of using wake and light therapy as a
supplement to standard treatment of hospitalized patients with depression.
METHOD: In this randomized, controlled study, 64 patients with moderate-to-severe
depression were allocated to standard treatment or to the intervention, which
additionally consisted of three wake therapy sessions in one week, 30-min daily
light treatment and sleep time stabilization over the entire nine-week study
period. RESULTS: Patients in the wake therapy group had a significant decrease in
depressive symptoms in week one as measured by HAM-D17 , 17.39 (CI 15.6-19.2) vs.
20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant
differences were found between the groups in weeks two to nine. At week nine, the
wake therapy group had a significantly larger increase in general self-efficacy
(P = 0.001), and waking up during nights was a significantly less frequent
problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer
patients in the wake therapy group slept during the daytime, and if they slept,
their naps were shorter (week three: 66 min vs. 117 min P = 0.02). CONCLUSION:
The antidepressant effect initially achieved could not be maintained during the
nine-week study period. However, sleep and general self-efficacy improved.
PMID- 28422271
TI - A systematic review of left unilateral electroconvulsive therapy.
AB - OBJECTIVE: To systematically review the published clinical trials, case series,
and case reports on left unilateral (LUL) electrode placement for clinical
electroconvulsive therapy (ECT). METHOD: PubMed, Ovid Medline, and the Cochrane
Library were searched for articles concerning LUL ECT. Number of patients,
efficacy, and cognitive outcomes were extracted from the papers that met our
inclusion criteria. RESULTS: A total of 52 articles were included in this review,
consisting of 33 clinical trials, seven case series, and 12 case reports.
CONCLUSION: Overall, the efficacy of LUL electrode placement for the treatment of
depression and psychosis is similar to that of right unilateral (RUL) and
bilateral (BL) electrode placements. Patients receiving LUL ECT tend to
experience more verbal memory impairment than patients receiving RUL ECT, but
less verbal impairment than patients receiving BL ECT. In contrast, patients
receiving LUL ECT tended to experience the least visual and nonverbal memory
impairment, compared to patients receiving RUL or BL ECT.
PMID- 28422270
TI - Characteristics and Incidence of Chronic Illness in Community-Dwelling
Predominantly Male U.S. Veteran Centenarians.
AB - OBJECTIVES: To assess the incidence of chronic illness and its effect on veteran
centenarians. DESIGN: Retrospective longitudinal cohort study. SETTING: United
States Veterans Affairs Corporate Data Warehouse (CDW). PARTICIPANTS: Community
dwelling veterans born between 1910 and 1915 who survived to at least age 80 (N =
86,892; 31,121 octogenarians, 52,420 nonagenarians, 3,351 centenarians).
MEASUREMENTS: The Kaplan-Meier method was used to estimate cumulative incidence
of chronic conditions according to age group. Incidence rates were compared using
the log-rank test. Cox proportional hazards models were used to estimate
unadjusted hazard ratios. RESULTS: Ninety-seven percent of Centenarians were
male, 88.0% were white, 31.8% were widowed, 87.5% served in World War II, and
63.9% did not have a service-related disability. The incidence rates of chronic
illnesses were higher in octogenarians than centenarians (atrial fibrillation,
15.0% vs 0.6%, P < .001; heart failure, 19.3% vs 0.4%, P < .001; chronic
obstructive pulmonary disease, 17.9% vs 0.6%, P < .001; hypertension, 29.6% vs
3.0%, P < .001; end-stage renal disease, 7.2% vs 0.1%, P < .001; malignancy,
14.1% vs 0.6%, P < .001; diabetes mellitus, 11.1% vs 0.4%, P < .001; stroke, 4.6%
vs 0.4%, P < .001) and in nonagenarians than centenarians (atrial fibrillation,
13.2% vs 3.5%, P < .001; heart failure, 15.8% vs 3.3%, P < .001; chronic
obstructive pulmonary disease, 11.8% vs 3.5%, P < .001; hypertension, 27.2% vs
12.8%, P < .001; end-stage renal disease, 11.9% vs 4.5%, P < .001; malignancy,
8.6% vs 2.3%, P < .001; diabetes mellitus, 7.5% vs 2.2%, P < .001; and stroke,
3.5% vs 1.3%, P < .001). CONCLUSION: In a large cohort of predominantly male
community-dwelling elderly veterans, centenarians had a lower incidence of
chronic illness than those in their 80s and 90s, demonstrating similar
compression of morbidity and extension of health span observed in other studies.
PMID- 28422272
TI - Modeling interactions between a beta-O-4 type lignin model compound and 1-allyl-3
methylimidazolium chloride ionic liquid.
AB - Aiming at understanding the molecular mechanism of the lignin dissolution in
imidazolium-based ionic liquids (ILs), this work presents a combined quantum
chemistry (QC) calculation and molecular dynamics (MD) simulation study on the
interaction of the lignin model compound, veratrylglycerol-beta-guaiacyl ether
(VG) with 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The monomer of VG is
shown to feature a strong intramolecular hydrogen bond, and its dimer is
indicated to present important pi-pi stacking and intermolecular hydrogen bonding
interactions. The interactions of both the cation and anion of [Amim]Cl with VG
are shown to be stronger than that between the two monomers, indicating that
[Amim]Cl is capable of dissolving lignin. While Cl- anion forms a hydrogen-bonded
complex with VG, the imidazolium cation interacts with VG via both the pi-pi
stacking and intermolecular hydrogen bonding. The calculated interaction energies
between VG and the IL or its components (the cation, anion, and ion pair)
indicate the anion plays a more important role than the cation for the
dissolution of lignin in the IL. Theoretical results provide help for
understanding the molecular mechanism of lignin dissolution in imidazolium-based
IL. The theoretical calculations on the interaction between the lignin model
compound and [Amim]Cl ionic liquid indicate that the anion of [Amim]Cl plays a
more important role for lignin dissolution although the cation also makes a
substantial contribution.
PMID- 28422273
TI - A Survey of Women's Awareness of and Reasons for Lack of Postfracture
Osteoporotic Care.
AB - OBJECTIVES: To identify women's beliefs and other factors associated with lack of
osteoporosis (OP) pharmacotherapy (OP-RX) during the 6 months after a fragility
fracture, including the woman's perspective on fracture risk, OP, and treatment.
DESIGN: Cross-sectional. SETTING: Group Health Cooperative, a mixed-model
delivery system. PARTICIPANTS: Female Group Health Cooperative enrollees aged 55
and older with an OP-related fracture according to diagnostic and procedure codes
from January 1, 2013, to March 30, 2014 (N = 985). MEASUREMENTS: OP-RX and
participant characteristics were ascertained from electronic health records
including medications dispensed. A mailed survey was used to obtain data on
health behaviors; OP-related history; concern about, knowledge of, and perceived
risk of future fracture; beliefs about OP-RX; sources of information on OP;
postfracture discussions with providers; and provider recommendations. RESULTS:
The response rate was 73%. Of 634 eligible respondents, 84% did not undergo OP-RX
during the 6 months after fracture. Fewer than 20% of women thought that OP
caused their fracture, 52% did not think they were at risk of future fracture,
and 75% did not think or know whether OP-RX reduces risk of fracture. Knowledge
about OP and the benefits of treatment was higher in the 16% of women who
underwent OP-RX after their fracture. Women reported low levels of engagement
with their healthcare providers regarding OP and fracture risk management.
CONCLUSION: These findings suggest low awareness about OP and its contribution to
fracture risk, lack of understanding about the benefits of pharmacotherapy, and
limited discussion about OP with primary care physicians. Information about
individual's beliefs and knowledge gaps can help design targeted patient and
provider education to improve treatment rates.
PMID- 28422274
TI - Efficacy and tolerance of ruxolitinib in refractory sclerodermatous chronic graft
versus-host disease.
PMID- 28422275
TI - Erratum.
PMID- 28422277
TI - Oxidized LDL, Gamma-Glutamyltransferase and Adverse Outcomes in Older Adults.
AB - OBJECTIVES: Gamma-glutamyltransferase (GGT) is a biomarker of liver disease and
oxidative stress which was associated with all-cause and cardiovascular (CV)
mortality in the general population and in patients with high risk conditions.
This study aims at assessing whether oxLDL modifies the relationship between GGT,
all-cause, and CV mortality in elderly individuals from the general population.
DESIGN: Observational longitudinal study. SETTING: Population-based cohort of
older individuals (>65 years) free of liver disease. PARTICIPANTS: One thousand
and thirty-eight individuals from the Invecchiare in Chianti (InCHIANTI) study.
MEASUREMENTS: Serum GGT level, oxidized low-density lipoprotein (oxLDL), CV
comorbidities, all-cause and CV mortality. RESULTS: The median age of the study
population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152
individuals (15%) had past CV events. During a median follow-up of 9 years, 401
individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT
predicted all-cause mortality (HR for 20 U/L increase in serum GGT: 1.11, 95% CI:
1.02-1.21, P = .02) and CV mortality (HR: 1.17, 95% CI: 1.03-1.33; P = .02).
Furthermore, in an analysis for interaction circulating oxLDL amplified the
effect of GGT on all-cause mortality (P = .003). CONCLUSION: Circulating oxLDL
amplifies the effect of GGT on mortality in the elderly. The mechanism for this
association remains unknown and requires further research, including studying the
potential role of GGT in oxidative stress. These results are consistent with the
hypothesis of a causal role of GGT in the CV morbidity and mortality in older
individuals and indicate that oxLDL plays a crucial role in the interpretation of
the link between GGT and the risk of adverse clinical events in this population.
PMID- 28422278
TI - Decipher test impacts decision making among patients considering adjuvant and
salvage treatment after radical prostatectomy: Interim results from the
Multicenter Prospective PRO-IMPACT study.
AB - BACKGROUND: Patients with prostate cancer and their providers face uncertainty as
they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after
undergoing radical prostatectomy. The authors prospectively evaluated the impact
of the Decipher test, which predicts metastasis risk after radical prostatectomy,
on decision making for ART and SRT. METHODS: A total of 150 patients who were
considering ART and 115 who were considering SRT were enrolled. Providers
submitted a management recommendation before processing the Decipher test and
again at the time of receipt of the test results. Patients completed validated
surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa
related anxiety. RESULTS: Before the Decipher test, observation was recommended
for 89% of patients considering ART and 58% of patients considering SRT. After
Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment
recommendations changed in the ART arm, including 31% among high-risk patients;
and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage
arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS)
scores were better after viewing Decipher test results (ART arm: median DCS
before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before
Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after
Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa
specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk
patients. Decipher results reported per 5% increase in 5-year metastasis
probability were associated with the decision to pursue ART (odds ratio, 1.48;
95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable
logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was
associated with treatment decision making and improved decisional effectiveness
among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. (c)
2017 American Cancer Society.
PMID- 28422279
TI - Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute
Ischemic Stoke.
AB - OBJECTIVES: To evaluate the safety and efficacy of endovascular therapy in
elderly adults treated for acute ischemic stroke. DESIGN: Retrospective cohort
study. SETTING: Comprehensive Stroke Center, University of Tor Vergata, Rome,
Italy. PARTICIPANTS: Elderly adults treated for acute ischemic stroke (N = 219).
MEASUREMENTS: Participants were divided into two groups based on their age (n =
62, >=80; n = 157, <80). Baseline and procedural characteristics, safety outcomes
such as intracranial hemorrhage (ICH) and mortality and efficacy outcomes such as
successful reperfusion and 3-month good clinical outcome of the two groups were
compared. Mutivariable analysis was performed to identify predictors of clinical
outcome. RESULTS: Intravenous thrombolysis was more frequent (67.7% vs 52.8%, P =
.04), and onset to reperfusion time was shorter (318.7 +/- 128.7 vs 282 +/- 53.5,
P = .02) in participants aged 80 and older, but no between-group differences were
found in terms of successful reperfusion (69% vs 63%, P = .4), good clinical
outcome (30.6% vs 34.3%, P = .6), any (37% vs 37.5%, P > .99) or symptomatic (11%
vs 14%, P = .6) ICH, or mortality (40.3% vs 29.2%, P = .14). Multivariable
analysis revealed that, in the older group, onset National Institute of Health
Stroke Scale (NIHSS) score (odds ratio (OR) = 0.65, 95% confidence interval (CI)
= 0.44-0.96, P = .03) and 24-hour clinical improvement (OR = 141.13, 95% CI =
2.96-6,720.7, P = .01) were independent predictors of 3-month functional
independence. CONCLUSION: These findings suggest that endovascular treatment for
stroke in selected elderly adults could be safe and effective. Major determinants
of outcome in this subgroup of elderly patients are presentation NIHSS score and
24-hour clinical improvement.
PMID- 28422281
TI - WNK1/HSN2 founder mutation in patients with hereditary sensory and autonomic
neuropathy: A Japanese cohort study.
AB - The clinical and genetic spectrum of hereditary sensory and autonomic neuropathy
(HSAN) is still unknown in Japan. We collected a broad cohort of 33 unrelated
patients with predominant sensory and/or autonomic dysfunctions, who were
referred to our genetic laboratory. A gene panel sequencing targeting 18 HSAN
related genes was performed using a next-generation sequencing system. A
recurrent frame shift mutation in the WNK1/HSN2 gene, c.3237_3238insT
(p.Asp1080*), was detected in 5 patients. This mutation was homozygous in 4 cases
and of a compound heterozygous genotype in 1 case. Geographic and haplotype
analysis of all 5 patients suggested a founder event. In addition, a novel
heterozygous nonsense variant, c.2615C>G (p.Ser872*), was identified. All the 5
patients presented with severe sensory and autonomic dysfunctions at birth or
during adolescence. In 2 patients, an uncommon phenotype of acute pathological
pain presented at ~50 years of age. Here, we present the first founder mutation
of WNK1/HSN2, in addition to French Canadian, which accounts for ~15.2% of
Japanese patients with HSAN in our cohort. We have also reviewed all previously
described mutations in WNK1/HSN2 and reconciled their nomenclature strategy on
the basis of the current longest transcript.
PMID- 28422280
TI - Integrating Frailty Research into the Medical Specialties-Report from a U13
Conference.
AB - Although the field of frailty research has expanded rapidly, it is still a
nascent concept within the clinical specialties. Frailty, conceptualized as
greater vulnerability to stressors because of significant depletion of
physiological reserves, predicts poorer outcomes in several medical specialties,
including cardiology, human immunodeficiency virus care, and nephrology, and in
the behavioral and social sciences. Lack of a consensus definition, proliferation
of measurement tools, inadequate understanding of the biology of frailty, and
lack of validated clinical algorithms for frail individuals hinders incorporation
of frailty assessment and frailty research into the specialties. In 2015, the
American Geriatrics Society, the National Institute on Aging (NIA), and the
Alliance for Academic Internal Medicine held a conference for awardees of the NIA
sponsored Grants for Early Medical/Surgical Specialists Transition into Aging
Research program to review the current state of knowledge regarding frailty in
the subspecialties and to highlight examples of integrating frailty research into
the medical specialties. Research questions to advance frailty research into
specialty medicine are proposed.
PMID- 28422282
TI - Analysis of Circulating miR-1, miR-23a, and miR-26a in Atrial Fibrillation
Patients Undergoing Coronary Bypass Artery Grafting Surgery.
AB - Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery.
From a pathophysiological point of view, a myriad of factors such as trauma,
atrial dilation, ischemia, mechanical myopericarditis, autonomic imbalance, loss
of connexins, AF nest remodeling, inflammation, sutures, and dysfunction caused
by postextracorporeal circulation can contribute to postoperative atrial
fibrillation (POAF) resulting in a longer hospital stay and consequently higher
cost. Recent studies showed that short fragments of RNA, called microRNA (miRNA),
can contribute to the development of several cardiovascular diseases, including
AF. The aim of this study was to evaluate the levels of circulating miRNAs (miR
1, -23a, and -26a) that can be involved in POAF. Patients submitted to coronary
artery bypass graft surgery were grouped in POAF (24 patients) and without POAF
(24 patients). Results showed older age, longer clamp-time, and more days in the
intensive care unit as well as a longer total hospital stay in the POAF group.
Preoperative levels of circulating miRNAs were similar. Analysis of miRNAs
revealed significantly lower circulating levels of miRNA-23a (P = 0.02) and
26a (P = 0.01) in the POAF group during the postoperative period. Receiver
operating characteristic (ROC) analysis showed the area under the ROC curve of
miR-23a and miR-26a for predicting FA was 0.63 (95% confidence interval [CI]:
0.51-0.74; P = 0.02) and 0.66 (95% CI: 0.55-0.77; P = 0.01), respectively.
Our data suggests that circulating miRNA-23a and -26a may be involved in the
underlying biology of postoperative AF development.
PMID- 28422283
TI - Agarose hydrogel induced MCF-7 and BMG-1 cell line progressive 3D and 3D revert
cultures.
AB - 3D culture systems have enhanced the utility of cancer cell lines as they are
considered closer to the in vivo systems. A variety of changes are induced in
cells cultured in 3D systems; an apparent and striking feature being the
spontaneous acquisition of distinct morphological entities. 3D reverts (3DRs) can
be obtained by introducing 3D aggregates in scaffold/matrix-free culture units.
It could be seen that the two cell lines used in this study exhibited differences
in 3DR structures, though both were cultured on agarose hydrogels. Also,
differences in 3DR formation, growth and survival were different. While 3D
aggregates of several cell lines have been reported for a variety of studies,
there are no studies that describe or utilize 3DRs. 3DRs can provide insights
into complex events that can occur in cancer cells; especially as material to
study metastasis, migration, and invasion.
PMID- 28422284
TI - Is a larger refuge always better? Dispersal and dose in pesticide resistance
evolution.
AB - The evolution of resistance against pesticides is an important problem of modern
agriculture. The high-dose/refuge strategy, which divides the landscape into
treated and nontreated (refuge) patches, has proven effective at delaying
resistance evolution. However, theoretical understanding is still incomplete,
especially for combinations of limited dispersal and partially recessive
resistance. We reformulate a two-patch model based on the Comins model and derive
a simple quadratic approximation to analyze the effects of limited dispersal,
refuge size, and dominance for high efficacy treatments on the rate of evolution.
When a small but substantial number of heterozygotes can survive in the treated
patch, a larger refuge always reduces the rate of resistance evolution. However,
when dominance is small enough, the evolutionary dynamics in the refuge
population, which is indirectly driven by migrants from the treated patch, mainly
describes the resistance evolution in the landscape. In this case, for small
refuges, increasing the refuge size will increase the rate of resistance
evolution. Our analysis distils major driving forces from the model, and can
provide a framework for understanding directional selection in source-sink
environments.
PMID- 28422285
TI - Hematopoietic stem/progenitor cell differentiation towards myeloid lineage is
modulated by LIGHT/LIGHT receptor signaling.
AB - The cytokine LT-related inducible ligand that competes for glycoprotein D binding
to herpesvirus entry mediator on T cells (LIGHT) is a member of the tumor
necrosis factor (TNF) superfamily. It is expressed primarily on activated T
lymphocytes, and detectable on monocytes, granulocytes, and immune dendritic
cells. It mainly plays a role in immune regulation including T cell activation
and dendritic cell maturation. We recently reported its role as an inducer in
embryonic stem cell differentiation, but its role in regulation of adult stem
cell has not been defined. In the present study, we examined the expression of
LIGHT receptor in Lin- c-kit+ Sca-1+ hematopoietic stem/progenitor cells
(HSC/HPCs). We found that HSC express HVEM, a LIGHT receptor, on its surface. We
further identified the role of LIGHT in promoting myeloid differentiation of HSCs
driven by granulocyte-monocyte colony stimulating factor (GM-CSF). Further
studies showed that LIGHT enhances both GM-CSF and GM-CSF receptor (GM-CSFR)
expression in HSCs. LIGHT stimulation increases PU.1 expression in HSC/HPCs. In
vivo administration of LIGHT increases the colony-forming unit
granulocyte/monocyte (CFU-GM) colony formation and plasma GM-CSF level.
Altogether, the data suggest LIGHT promote myeloid differentiation of HSC/HPCs.
PMID- 28422286
TI - Isorhapontigenin induced cell growth inhibition and apoptosis by targeting EGFR
related pathways in prostate cancer.
AB - Isorhapontigenin (ISO), a naturally phytopolyphenol compound existing in Chinese
herb, apples, and various vegetables, has attracted extensive interest in recent
years for its diverse pharmacological characteristics. Increasing evidences
reveal that ISO can inhibit cancer cell growth by induced apoptosis, however, the
molecular mechanisms is not fully understood. In this study, we found for the
first time that ISO apparently induced cell growth inhibition and apoptosis by
targeting EGFR and its downstream signal pathways in prostate cancer (PCa) cells
both in vitro and in vivo, whereas no obviously effect on normal prostate cells.
From the results, we found that ISO competitively targeted EGFR with EGF and
inhibited EGFR auto-phosphorylation, and then decreased the levels of p-Erk1/2, p
PI3 K, and p-AKT, and further induced down-regulation of p-FOXO1 and promoted
FOXO1 nuclear translocation; and finally resulted in a significantly up
regulation of Bim/p21/27/Bax/cleaved Caspase-3/cleaved PARP-1 and a markedly down
regulation of Sp1/Bcl-2/XIAP/Cyclin D1. Moreover, our experimental data
demonstrated that treatment of ISO decreased protein level of AR via both
inhibiting the expression of AR gene and promoting the ubiquitination/degradation
of AR proteins in proteasome. In vivo, we also found that ISO inhibited the
growth of subcutaneous xenotransplanted tumor in nude mice by inducing PCa cell
growth inhibition and apoptosis. Taken together, all findings here clearly
implicated that EGFR-related signal pathways, including EGFR-PI3K-Akt and EGFR
Erk1/2 pathways, were involved in ISO-induced cell growth inhibition and
apoptosis in PCa cells, providing a more solid theoretical basis for the
application of ISO to treat patients with prostate cancer in clinic.
PMID- 28422288
TI - General dentists' awareness of how to cope with medical emergencies in paediatric
dental patients.
AB - BACKGROUND: General dentists (GDs) should be aware of the symptoms, signs,
diagnoses and treatment of medical emergencies in paediatric patients. AIM: To
evaluate the knowledge of GDs in coping with medical emergencies, and to identify
whether they are confident to diagnose and treat medical emergencies in
paediatric patients. DESIGN: The questionnaire was conducted immediately before
the beginning of national dental meetings and continuing education seminars in
Croatia, attended by the GDs, in order to obtain a representative sample.
RESULTS: Of a total of 498 GDs who returned the questionnaire with valid data,
51.2% reported that a medical history was regularly taken. A high proportion
(81.3%) of the GDs had never received any basic life support (BLS) training and
education for paediatric patients during their undergraduate studies. After
graduation, this value rose to 86.1% of GDs. However, more than two-thirds
(68.7%) had experienced some emergency situation in their practice. The most
frequent emergency was vasovagal syncope (83.6%) and the most rare was cardiac
arrest (8.2%). One-fifth (20.5%) of GDs experienced some emergency but could not
make a diagnosis. The more BLS training undergone by a GD, the more self
confident s/he felt in an emergency situation. CONCLUSIONS: Most GDs have a lack
of knowledge to cope with medical emergencies in paediatric patients, and do not
feel confident to diagnose and treat emergency situations in children. It is
suggested that adequate training and education should be provided for all GDs to
address this shortcoming.
PMID- 28422287
TI - Genetic variants as potential predictive biomarkers in advanced colorectal cancer
patients treated with oxaliplatin-based chemotherapy.
AB - Chemotherapy regimen containing oxaliplatin is often the first-line treatment for
patient with advanced colorectal cancer. Oxaliplatin binds to DNA, leading to the
formation of crosslinks and bulky adducts. Approximately 50% of patients with CRC
benefit from treatment with oxaliplatin. It is possible that genetic variants in
biological pathways involved in drug transportation, drug metabolism, DNA damage
repair, and cell cycle modulation might affect the activity, or efficacy of
oxaliplatin. Because oxaliplatin resistance may be related to these genetic
variants and may therefore be an important reason for treatment failure, we have
summarized the genetic variations that have been reported to be predictive
markers of the response to oxaliplatin based therapy in patients with advanced
CRC.
PMID- 28422289
TI - Dietary Tuna Dark Muscle Protein Attenuates Hepatic Steatosis and Increases Serum
High-Density Lipoprotein Cholesterol in Obese Type-2 Diabetic/Obese KK-Ay Mice.
AB - Tuna muscle consists of light and dark muscle in approximately equal proportions.
However, besides for the light muscle of tuna, cod, sardine, and salmon, few
researches have assessed the health-promoting functions of fish protein.
Therefore, we evaluated the mechanisms underlying the alteration of lipid storage
and cholesterol metabolism following the intake of tuna dark muscle protein
(TDMP) by obese type-2 diabetic/obese mice. Four-week-old male KK-Ay mice were
separated into 2 dietary groups, with one group receiving a casein-based diet and
the other receiving a diet with the substitution of part of the protein (50%,
w/w) by TDMP (TDMP diet) for 4 wk. The TDMP diet significantly increased the
content of serum high-density lipoprotein cholesterol, partly due to the
reduction of the expression of scavenger receptor class B member 1 in epididymal
white adipose tissue. In addition, dietary TDMP decreased the content of hepatic
triacylglycerol, which could be due to the enhancement of carnitine
palmitoyltransferase-2 activity through the activation of the expression of the
peroxisome proliferative activated receptor-alpha in the liver. These results
suggest that TDMP could have the potential to prevent the development of obesity
related diseases by suppressing the storage of hepatic triacylglycerol and
cholesterol.
PMID- 28422290
TI - Heroin-related Deaths from the Hennepin County Medical Examiner's Office from
2004 Through 2015.
AB - Over the past two decades, prescription and illicit opioid use has led to changes
in public health policy to address the increasing number of opioid-related
deaths. The purpose of this study was to review cases from Hennepin County
Medical Examiner's Office between 2004 through 2015 where heroin was listed as a
significant contributor or as the cause of death. We identified 322 heroin
related deaths, which were predominantly male (255; 79%). 6-Monoacetylmorphine (6
MAM) median (range) concentrations were as follows: blood (n = 7), 0.010 (0.006
0.078) mg/L; urine (n = 30), 0.359 (0.009-1.75) mg/L; and vitreous humor (n =
31), 0.034 (0.004-0.24) mg/L. Free morphine was measurable in 273 cases and the
percent free morphine (range), when grouped by COD, was opioid (n = 124), 28%
(2.2%-92%), and mixed drug toxicity (n = 135), 35.3% (1.5%-100%); (p < 0.01).
Quantitation of 6-MAM in blood and vitreous humor, along with a free to total
morphine ratio >26%, was useful in establishing heroin-related deaths.
PMID- 28422291
TI - Barriers and Facilitators to Integrating Health Service Responses to Intimate
Partner Violence in Low- and Middle-Income Countries: A Comparative Health
Systems and Service Analysis.
AB - This systematic review synthesizes 11 studies of health-sector responses to
intimate partner violence (IPV) in low- and middle-income countries. The services
that were most comprehensive and integrated in their responsiveness to IPV were
primarily in primary health and antenatal care settings. Findings suggest that
the following facilitators are important: availability of clear guidelines,
policies, or protocols; management support; intersectoral coordination with
clear, accessible on-site and off-site referral options; adequate and trained
staff with accepting and empathetic attitudes toward survivors of IPV; initial
and ongoing training for health workers; and a supportive and supervised
environment in which to enact new IPV protocols. A key characteristic of the most
integrated responses was the connection or "linkages" between different
individual factors. Irrespective of their service entry point, what emerged as
crucial was a connected systems-level response, with all elements implemented in
a coordinated manner.
PMID- 28422292
TI - High-theabrownins instant dark tea product by Aspergillus niger via submerged
fermentation: alpha-glucosidase and pancreatic lipase inhibition and antioxidant
activity.
AB - BACKGROUND: Theabrownins (TB) are bioactive components that are usually extracted
from Chinese dark tea, in which they are present at low concentrations. The
present study aimed to produce an instant dark tea high in theabrownins via
submerged fermentation by the fungus Aspergillus niger. Three fermentation
parameters that affect theabrownins content (i.e. inoculum size, liquid-solid
ratio and rotation speed) were optimized using response surface methodology.
RESULT: Optimum fermentation conditions were modeled to be an inoculum of 5.40%
(v/v), a liquid-solid ratio of 27.45 mL g-1 and a rotation speed of 184 rpm and
were predicted to yield 292.99 g kg-1 TB. Under these experimentally conditions,
the TB content of the instant dark tea was 291.93 g kg-1 . The antioxidant
capacity and alpha-glucosidase and pancreatic lipase inhibitory activities of the
high-TB instant black tea were higher than four other typical instant dark tea
products. CONCLUSION: The results of the present study show that careful
management of culture conditions can produce a dark tea high in theabrownins.
Furthermore, high-theabrownins instant dark tea could serve as a source of
bioactive products and be used in functional foods as an ingredient imparting
antioxidant properties and the ability to inhibit pancreatic lipase and alpha
glucosidase. (c) 2017 Society of Chemical Industry.
PMID- 28422293
TI - An autocrine ATP release mechanism regulates basal ciliary activity in airway
epithelium.
AB - KEY POINTS: Extracellular ATP, in association with [Ca2+ ]i regulation, is
required to maintain basal ciliary beat frequency. Increasing extracellular ATP
levels increases ciliary beating in airway epithelial cells, maintaining a
sustained response by inducing the release of additional ATP. Extracellular ATP
levels in the millimolar range, previously associated with pathophysiological
conditions of the airway epithelium, produce a transient arrest of ciliary
activity. The regulation of ciliary beat frequency is dependent on ATP release by
hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of
which may even stop ciliary movement. The force exerted by cilia, measured by
atomic force microscopy, is reduced following extracellular ATP hydrolysis. This
result complements the current understanding of the ciliary beating regulatory
mechanism, with special relevance to inflammatory diseases of the airway
epithelium that affect mucociliary clearance. ABSTRACT: Extracellular
nucleotides, including ATP, are locally released by the airway epithelium and
stimulate ciliary activity in a [Ca2+ ]i -dependent manner after mechanical
stimulation of ciliated cells. However, it is unclear whether the ATP released is
involved in regulating basal ciliary activity and mediating changes in ciliary
activity in response to chemical stimulation. In the present study, we evaluated
ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from
mouse tracheal epithelium, using videomicroscopy and atomic force microscopy
(AFM), respectively. Extracellular ATP levels and [Ca2+ ]i were measured by
luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide
was measured to evaluate hemichannel functionality. We show that hydrolysis of
constitutive extracellular ATP levels with apyrase (50 U ml-1 ) reduced basal CBF
by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by
carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an antagonist used to
block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing
extracellular ATP levels (0.1-100 MUm) increased CBF, maintaining a sustained
response that was suppressed in the presence of carbenoxolone. We also show that
high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal
CBF by reducing [Ca2+ ]i and hemichannel functionality. In summary, we provide
evidence indicating that airway epithelium ATP release is the molecular autocrine
mechanism regulating basal ciliary activity and is also the mediator of the
ciliary response to chemical stimulation.
PMID- 28422294
TI - Antiviral activity of exopolysaccharides from Arthrospira platensis against koi
herpesvirus.
AB - Although koi herpesvirus (KHV) has a history of causing severe economic losses in
common carp and koi farms, there are still no treatments available on the market.
Thus, the aim of this study was to test exopolysaccharides (EPS) for its
antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in
common carp brain cells. These substances can be easily extracted from
extracellular algae supernatant and were identified as groups of sulphated
polysaccharides. In order to reach this aim, Arthrospira platensis, which is well
known for its antiviral activity of intra- and extracellular compounds towards
mammalian herpesviruses, was investigated as standard organism and compared to
commercial antiviral drug, ganciclovir, which inhibits the viral DNA
polymerization. The antiviral activity of polysaccharides of A. platensis against
KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes,
and it was found by RT-PCR that EPS, applied at a concentration of >18 MUg mL-1
and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral
replication in common carp brain (CCB) cells even after 22 days post-infection,
entirely. Further, this study presents first data indicating an enormous
potential using polysaccharides as an additive for aquacultures to lower or
hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future.
PMID- 28422295
TI - In vivo and in vitro studies using larval and adult antigens from Neobenedenia
melleni on immune response in yellowtail (Seriola lalandi).
AB - Neobenedenia melleni is a monogenean parasite that causes significant mortality
and economic losses in fish aquaculture. Changes in the antigenic composition of
this parasite occur during its developmental stages. In this study, we evaluated
humoral parameters in serum and transcriptional immune responses of yellowtail
naturally infected with N. melleni. In addition, in vitro assays were performed
to study the stimulatory effects of antigens from larvae and adults on spleen
leucocytes from non-infected fish at 6 and 24 h post-stimulation. The results
showed enhanced total protein, myeloperoxidase and antiprotease activities in N.
melleni-infected fish compared with non-infected ones. The induction of Toll-like
receptors (TLRs) and pro-inflammatory cytokines in spleen leucocytes during
natural infection with N. melleni suggests that these immune-related genes play
an important role in the initiation of the immune defence mechanism for
controlling parasite infection. Interestingly, the magnitude of in vitro
responses of spleen leucocytes was dependent on the parasitic stage. An important
stimulation of gene expression by adult antigens on spleen leucocytes was
observed. Differential expression patterns of TLRs and target cytokines in
yellowtail leucocytes in both in vivo and in vitro studies suggest that the
quality of yellowtail immune response is conditioned by N. melleni development.
PMID- 28422296
TI - Keeping out and getting in: reframing emergency department gatekeeping as
structural competence.
AB - Sociologists have tended to frame medical gatekeeping as an exclusionary social
practice, delineating how practitioners and clerical staff police the moral
boundaries of medicine by keeping out patients who are categorised as 'bad',
'deviant', or otherwise problematic. Yet medical gatekeeping, understood more
broadly, can include not only keeping patients out of particular clinical
settings, but also redirecting them to alternative sources of care. In this
article, I draw on qualitative analysis of audio-recorded patient-provider
interactions in a United States emergency department (ED) to illustrate medical
gatekeeping as a two-step process of, first, categorising certain patient
complaints as unsuitable for treatment within a particular setting, and second,
diverting patients to alternative sites for care. I refer to these as the
restrictive and facilitative components of medical gatekeeping to denote how each
relates to patients' access to care, recognising that both components of medical
gatekeeping are part of a coordinated organisational strategy for managing
resource scarcity. By illustrating how ED providers reveal intimate knowledge of
structural vulnerabilities in diverting socioeconomically disadvantaged patients
with chronic back pain to clinical sites that are better equipped to provide
care, I suggest that we rethink the emphasis on restrictive practices in
sociological accounts of medical gatekeeping.
PMID- 28422297
TI - Piecing together the aggression puzzle: Testing the mediating variables linking
early to later aggression.
AB - Results from several studies show that early aggression predicts later
aggression; however, few studies have examined the mediating mechanisms in these
relations. The paucity of research that has tested mediation found that
aggressive motives and hostile attributions are important causal processes. This
past work is limited by not measuring aggression multiple times throughout the
study to test aggression change over time and the variables that mediate such
change. The current study had participants (N = 90) interact with a same-sex
confederate on a modified version of the Tangram Task-our measure of aggressive
behavior-for three trials. At each trial, participants completed a measure of
aggressive motivations, assigned tangram puzzles for their partner to solve, were
provoked (or not) by their ostensible partner, and then completed an assessment
of aggressive attributions regarding their partner's behavior. Results showed
that, for provoked participants, the relation between Time 1 aggressive
attributions predicted Time 3 aggressive behavior through the following temporal
mediated pathway: Time 2 aggressive attributions, Time 2 aggressive behavior, and
Time 3 aggressive motivations.
PMID- 28422298
TI - Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in
the Quest for the Molecules With Therapeutic and Preventive Potential.
AB - Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid
diseases that affect millions of people worldwide. Broadly supported by
epidemiological data, the higher incidence of AD among type 2 diabetic patients
led to the recognition of T2D as a tangible risk factor for the development of
AD. Indeed, there is now growing evidence on brain structural and functional
abnormalities arising from brain insulin resistance and deficiency, ultimately
highlighting the need for new approaches capable of preventing the development of
AD in type 2 diabetic patients. This review provides an update on overlapping
pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic
events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity,
and even shared genetic background. These events will be presented as puzzle
pieces put together, thus establishing potential therapeutic targets for drug
discovery and development against T2D and diabetes-induced cognitive decline-a
heavyweight contributor to the increasing incidence of dementia in developed
countries. Hoping to pave the way in this direction, we will present some of the
most promising and well-studied drug leads with potential against both
pathologies, including their respective bioactivity reports, mechanisms of
action, and structure-activity relationships.
PMID- 28422299
TI - Incorporation of pre-therapy 18 F-FDG uptake data with CT texture features into a
radiomics model for radiation pneumonitis diagnosis.
AB - PURPOSE: To determine whether the addition of standardized uptake value (SUV)
from PET scans to CT lung texture features could improve a radiomics-based model
of radiation pneumonitis (RP) diagnosis in patients undergoing radiotherapy.
METHODS AND MATERIALS: Anonymized data from 96 esophageal cancer patients (18 RP
positive cases of Grade >= 2) were collected including pre-therapy PET/CT scans,
pre-/post-therapy diagnostic CT scans and RP status. Twenty texture features
(first-order, fractal, Laws' filter and gray-level co-occurrence matrix) were
calculated from diagnostic CT scans and compared in anatomically matched regions
of the lung. Classifier performance (texture, SUV, or combination) was assessed
by calculating the area under the receiver operating characteristic curve (AUC).
For each texture feature, logistic regression classifiers consisting of the
average change in texture feature value and the pre-therapy SUV standard
deviation (SUVSD ) were created and compared with the texture feature as a lone
classifier using ANOVA with correction for multiple comparisons (P < 0.0025).
RESULTS: While clinical parameters (mean lung dose, smoking history, tumor
location) were not significantly different among patients with and without
symptomatic RP, SUV and texture parameters were significantly associated with RP
status. AUC for single-texture feature classifiers alone ranged from 0.58 to 0.81
and 0.53 to 0.71 in high-dose (>= 30 Gy) and low-dose (< 10 Gy) regions of the
lungs, respectively. AUC for SUVSD alone was 0.69 (95% confidence interval: 0.54
0.83). Adding SUVSD into a logistic regression model significantly improved model
fit for 18, 14 and 11 texture features and increased the mean AUC across features
by 0.08, 0.06, and 0.04 in the low-, medium-, and high-dose regions,
respectively. CONCLUSIONS: Addition of SUVSD to a single-texture feature improves
classifier performance on average, but the improvement is smaller in magnitude
when SUVSD is added to an already effective classifier using texture alone. These
findings demonstrate the potential for more accurate assessment of RP using
information from multiple imaging modalities.
PMID- 28422301
TI - Meeting the Reproductive Health Needs of Female Key Populations Affected by HIV
in Low- and Middle-Income Countries: A Review of the Evidence.
AB - Female sex workers and other women at high risk of acquiring HIV have the right
to sexual and reproductive health, including the right to determine the number
and timing of pregnancies. We conducted a literature review to examine the data
that exist regarding the family planning and reproductive health needs of female
key populations, the underlying determinants of these populations' vulnerability
to poor reproductive health outcomes, and the obstacles they face in accessing
high-quality reproductive health services. Findings indicate that female key
populations experience high rates of unmet need for family planning and safer
conception services, unintended pregnancies, sexual violence, and abortion, and
that they practice inconsistent condom use. Restrictive policy environments,
stigma and discrimination in health care settings, gender inequality, and
economic marginalization restrict access to services and undermine the ability to
safely achieve reproductive intentions. We offer recommendations for structural,
health system, community, and individual-level interventions that can mitigate
the effects of these barriers and improve reproductive health outcomes.
PMID- 28422300
TI - Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin
in patients with stable coronary disease before percutaneous coronary
intervention: The STATIPLAT randomized study.
AB - BACKGROUND: The acute effects of statin loading dose (LD) on platelet reactivity
in patients with chronic stable angina (CSA) are not completely clear.
HYPOTHESIS: We hypothesized that LDs of atorvastatin and rosuvastatin have
different pharmacodynamic acute effects on platelet aggregability in CSA patients
with baseline normal platelet reactivity while on dual antiplatelet therapy
(DAPT). METHODS: From September 2011 to February 2014, all consecutive CSA
patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective
percutaneous coronary intervention (PCI). An initial assessment of platelet
reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively,
indicative of the response to clopidogrel and aspirin) was performed with
impedance aggregometry. Patients with high platelet reactivity to ADP test (area
under the curve >47) were excluded. The remaining patients were randomized into 3
treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg;
and Group C, no statin LD (control group). A second assessment of platelet
reactivity was performed >=12 hours after statin LD. RESULTS: 682 patients were
screened and 145 were randomized into the 3 groups. At baseline and after statin
LD, no significant difference was found in platelet reactivity in response to 3
different agonists between the 3 groups. Subgroup analysis showed that platelet
reactivity to ADP test was significantly lower in patients chronically treated
with low-dose statins (n = 94) compared with statin-naive patients (n = 51; 15.32
+/- 1.50 vs 18.59 +/- 1.30; P = 0.007). CONCLUSIONS: Loading dose of atorvastatin
(80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet
reactivity in CSA patients with baseline reduced platelet reactivity as in
chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose
statins and clopidogrel resulted in significantly lower platelet reactivity
compared with clopidogrel alone.
PMID- 28422302
TI - Recombinant PirA-like toxin protects shrimp against challenge with Vibrio
parahaemolyticus, the aetiological agent of acute hepatopancreatic necrosis
disease.
PMID- 28422303
TI - Smoking increased the risk of prostate cancer with grade group >= 4 and
intraductal carcinoma in a prospective biopsy cohort.
AB - OBJECTIVE: To investigate the association between smoking and different prostate
cancer (PCa) pathological subtypes incidence in Chinese men. PATIENTS AND
METHODS: We prospectively included 1795 patients who underwent prostate biopsies
in one tertiary center between March 2013 and April 2016. Clinical data and
biopsy outcomes were collected. Logistic regression was used to evaluate the
association between cigarette smoking and PCa incidence. RESULTS: A total of 737
men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade
group >= 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the
prostate (IDC-P), respectively. Current smokers had a significantly higher risk
of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association
was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61
1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher
risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50,
95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never
smokers (OR = 2.29, 95%CI: 1.14-4.59). CONCLUSION: Among men in this Chinese
biopsy cohort, current smoking was associated with highly malignant PCa
incidence, such as HGPCa and IDC-P. The duration of smoking may be associated
with HGPCa.
PMID- 28422304
TI - Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of
treatments with tigecycline and clarithromycin.
AB - Zebrafish (Danio rerio) are a popular model organism used in a growing number of
research fields. Maintaining healthy, disease-free laboratory fish is important
for the integrity of many of these studies. Mycobacteriosis is a chronic
bacterial infection caused by several Mycobacterium spp. and is the second most
common disease found in laboratory zebrafish. Current mycobacteriosis control
measures recommend the removal of infected fish and in severe outbreaks,
depopulation. These measures can be effective, but less disruptive measures
should be assessed for controlling mycobacteriosis, particularly when valuable
and rare lines of fish are affected. Here, the in vivo efficacy of two drug
candidates, tigecycline (1 MUg g-1 ) and clarithromycin (4 MUg g-1 ), was tested
in adult zebrafish experimentally infected with Mycobacterium chelonae. We
assessed both short (14 day)- and long-term (30 day) treatments and evaluated
fecundity and pathological endpoints. Fecundity and histology results show that
zebrafish tolerated antibiotics. Antibiotic treatments did not significantly
impact the prevalence of acid-fast granulomas; however, the severity of
infections (acid-fast granuloma intensity) was significantly decreased following
treatments.
PMID- 28422305
TI - New host record and molecular characterization of Dicauda atherinoidi Hoffman &
Walker (Bivalvulida: Myxobolidae): a parasite of the emerald shiner Notropis
atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865.
AB - Updated morphological and histopathological descriptions for Dicauda atherinoidi
(Bivalvulida:Myxobolidae) and an expanded host range are supplemented with the
first molecular data and phylogenetic analyses of the genus. Plasmodia were
located on the head, ventrum/body and fins of infected emerald shiner Notropis
atherinoides Rafinesque, 1818 and mimic shiner Notropis vollucellus Cope, 1865, a
new host species. Myxospores were spherical, ranging 9.3-11.4 MUm (10.5 +/- 0.4)
in length, 9.0-11.0 MUm (9.7 +/- 0.4) in width and 6.6-7.0 MUm (6.8 +/- 0.2)
thick in sutural view, and possessed 2-3 caudal processes (5.3-68.3 MUm, 31.1 +/-
13.6) connected to the spore body at the sutural groove, all of which are
consistent with the genus Dicauda. In the absence of available Dicauda sequence
data, the 18S rDNA sequences from Michigan isolates were most similar to
Myxobolus spp. Phylogenetic analyses clustered these isolates with myxobolid
species from cyprinid fish, suggesting these parasites may represent an
underpopulated group of cyprinid-infecting myxozoans. Histopathology revealed
thin-walled plasmodial pseudocysts in the dermis and associated connective
tissue, where granulomatous inflammation and focal scale atrophy were also
present. Further sampling/sequencing of myxobolids from Notropis spp. should
expand these underrepresented myxozoans and offer further insight into
Myxobolidae host family tropisms.
PMID- 28422307
TI - What is your diagnosis? Fine-needle aspirate of a lung nodule and bronchoalveolar
lavage from a dog.
PMID- 28422306
TI - Development of a novel frailty index to predict mortality in patients with end
stage liver disease.
AB - : Cirrhosis is characterized by muscle wasting, malnutrition, and functional
decline that confer excess mortality not well quantified by the Model for End
Stage Liver Disease (MELD) Sodium (MELDNa) score. We aimed to develop a frailty
index to capture these extrahepatic complications of cirrhosis and enhance
mortality prediction in patients with cirrhosis. Consecutive outpatients listed
for liver transplantation at a single transplant center without MELD exceptions
were assessed with candidate frailty measures. Best subset selection analyses
with Cox regression identified subsets of frailty measures that predicted
waitlist mortality (=death or delisting because of sickness). We selected the
frailty index by balancing statistical accuracy with clinical utility. The net
reclassification index (NRI) evaluated the %patients correctly reclassified by
adding the frailty index to MELDNa. Included were 536 patients with cirrhosis
with median MELDNa of 18. One hundred seven (20%) died/were delisted. The final
frailty index consisted of: grip strength, chair stands, and balance. The ability
of MELDNa and the frailty index to correctly rank patients according to their 3
month waitlist mortality risk (i.e., concordance-statistic) was 0.80 and 0.76,
respectively, but 0.82 for MELDNa+frailty index together. Compared with MELDNa
alone, MELDNa+frailty index correctly reclassified 16% of deaths/delistings (P =
0.005) and 3% of nondeaths/delistings (P = 0.17) with a total NRI of 19% (P <
0.001). Compared to those with robust frailty index scores (<20th percentile),
cirrhotics with poor frailty index scores (>80th percentile) were more impaired
by gait speed, difficulty with Instrumental Activities of Daily Living,
exhaustion, and low physical activity (P < 0.001 for each). CONCLUSION: Our
frailty index for patients with cirrhosis, comprised of three performance-based
metrics, has construct validity for the concept of frailty and improves risk
prediction of waitlist mortality over MELDNa alone. (Hepatology 2017;66:564-574).
PMID- 28422308
TI - Androgen receptor-regulated miRNA-193a-3p targets AJUBA to promote prostate
cancer cell migration.
AB - Background Dysregulation of microRNA (miRNA) expression is implicated in cancer
development and progression by modulating oncogenes or tumor suppressors at the
post-transcriptional level. Methods To investigate the role of miRNAs in prostate
cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in
androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate
cancer (CRPC) C4-2B cells. For functional validation, we specifically
investigated miR-193a-3p, which is highly upregulated in C4-2B cells and
modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p
and its downstream target gene in PCa cell migration using biochemical
approaches. Results We identified a subset of differentially expressed miRNAs in
C4-2B cells compared to LNCaP cells. Computational analysis shows that the
targets of upregulated miRNAs are significantly associated with downregulated
protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that
these downregulated mRNAs are significantly enriched in cell-cell adhesion
functions. Downregulation of these miRNA-targeted genes may change PCa cell
motility resulting in the acquisition of metastatic potential. We then focus on
miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell
migration through downregulating its target AJUBA. AJUBA is a LIM domain protein
and contributes to the formation and stability of cadherin-mediated cell-cell
adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA
expression is observed in metastatic PCa tumors. Conclusions Our results suggest
a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p
is a potential therapeutic target for metastatic PCa.
PMID- 28422309
TI - Necrotizing Sweet syndrome in a patient with myelodysplastic syndrome.
PMID- 28422311
TI - Reply.
PMID- 28422310
TI - Adult-onset cystic fibrosis liver disease: Diagnosis and characterization of an
underappreciated entity.
AB - : Cystic fibrosis (CF) liver disease (CFLD), a leading cause of death in CF, is
mostly described in pediatric populations. Adult-onset CFLD lacks sufficient
characterization and diagnostic tools. A cohort of CF patients without CFLD
during childhood were followed for up to 38 years with serologic testing,
imaging, and noninvasive fibrosis markers. Historical CFLD diagnostic criteria
were compared with newly proposed CFLD criteria. Thirty-six CF patients were
followed for a median of 24.5 years (interquartile range 15.6-32.9). By the last
follow-up, 11 (31%) had died. With conventional criteria, 8 (22%) patients had
CFLD; and by the new criteria, 17 (47%) had CFLD at a median age of 36.6 years
(interquartile range 26.5-43.2). By the new criteria, those with CFLD had higher
median alanine aminotransferase (42 versus 27, P = 0.005), aspartate
aminotransferase (AST; 26 versus 21, P = 0.01), direct bilirubin (0.13 versus
0.1, P = 0.01), prothrombin time (14.4 versus 12.4, P = 0.002), and AST-to
platelet ratio index (0.31 versus 0.23, P = 0.003) over the last 2 years of
follow-up. Subjects with a FibroScan >6.8 kPa had higher alanine aminotransferase
(42 versus 28U/L, P = 0.02), AST (35 versus 25U/L, P = 0.02), AST-to-platelet
ratio index (0.77 versus 0.25, P = 0.0004), and Fibrosis-4 index (2.14 versus
0.74, P = 0.0003) and lower platelet counts (205 versus 293, P = 0.02). One CFLD
patient had nodular regenerative hyperplasia. Longitudinally, mean platelet
counts significantly declined in the CFLD group (from 310 to 230 U/L, P =
0.0005). Deceased CFLD patients had lower platelet counts than those alive with
CFLD (143 versus 258 U/L, P = 0.004) or those deceased with no CFLD (143 versus
327U/L, P = 0.006). CONCLUSION: Adult-onset CFLD may be more prevalent than
previously described, which suggests a later wave of CFLD that impacts morbidity;
routine liver tests, radiologic imaging, noninvasive fibrosis markers, and
FibroScan can be used algorithmically to identify adult CFLD; and further
evaluation in other CF cohorts should be performed for validation. (Hepatology
2017;66:591-601).
PMID- 28422312
TI - What is your diagnosis? Cutaneous ulcerated nodule in a geriatric dog.
PMID- 28422313
TI - Regulome networks and mutational landscape in liver cancer: An informative path
to precision medicine.
PMID- 28422314
TI - Hepatic steatosis, hepatitis C, and human immunodeficiency viruses: A complex
interplay.
PMID- 28422315
TI - Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine
Arginine-Rich Protein ASF/SF2.
AB - Positive transcription elongation factor-b (P-TEFb) is required for the release
of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for
efficient proceeding to the transcription elongation. It consists of two core
subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is
the major and most studied combination. We have previously identified a novel
splice variant of cyclin T1, cyclin T1b, which negatively regulates the
transcription elongation of HIV-1 genes as well as several host genes. In this
study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory
factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the
production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin
T1-depedent genes at the transcription level. We further found that a cis-element
on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2.
Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which
contributes to the control of the subsequent transcription events. J. Cell.
Biochem. 118: 4020-4032, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422317
TI - A molecular mechanics and ab initio prediction of the 1 H chemical shifts of
pinanes.
AB - Molecular mechanics calculations plus the application of a refined Karplus
equation gave the conformations of 19 pinanes. These range from a Y-shaped
geometry in the apopinene and alpha-pinene series to a pseudo chair conformation
in beta-pinene, nopinone and verbanone, a flattened chair in pinocarvone and the
pinocarveols and a distorted Y shape for iso-verbanone. These structures were
then used as input to predict the 1 H chemical shifts of these compounds by semi
empirical (1 H-NMR spectra (HSPEC)) and ab initio gauge-invariant atomic orbital
(GIAO) calculations, the latter at the B3LYP hybrid density functional theory
level using 6-31++G** basis set. The two methods gave generally good agreement
with the 184 observed shifts with root mean square (RMS) errors 0.07 ppm (HSPEC)
and 0.10 ppm (GIAO), but the GIAO calculations gave several significant (>0.25
ppm) errors. One was for the H3 proton in apopinenone and other alpha,beta
unsaturated ketones; the others occurred for protons in close proximity to
hydroxyl groups. To provide more information, smaller analogues of known geometry
and chemical shifts were subject to the same analysis. In cyclopentenone, the
Gaussian geometry gave good agreement with the observed shifts, but the MMFF94,
MMX and MM3 geometries all gave errors for different protons. These results show
clearly that the molecular geometries of the alpha,beta unsaturated ketones are
responsible for the errors. The errors for the alcohols were examined using
ethanol as model and were shown to be due to the different possible conformations
of the OH group. Similar GIAO calculations on substituted methanes gave good
agreement for the methyl compounds but poor agreement for di and tri
halosubstituted methanes. The aforementioned method of molecular mechanics plus
GIAO calculations is shown to be a very useful tool for the investigation of
molecular geometries and conformations. However, multihalogen compounds may
require different basis sets for accurate calculations. Copyright (c) 2017 John
Wiley & Sons, Ltd.
PMID- 28422318
TI - Computational Analysis of Breast Cancer GWAS Loci Identifies the Putative
Deleterious Effect of STXBP4 and ZNF404 Gene Variants.
AB - The genome-wide association studies (GWAS) have enabled us in identifying
different breast cancer (BC) susceptibility loci. However, majority of these are
non-coding variants with no annotated biological function. We investigated such
78 noncoding genome wide associated SNPs of BC and further expanded the list to
2,162 variants with strong linkage-disequilibrium (LD, r2 >=0.8). Using multiple
publically available algorithms such as CADD, GWAVA, and FATHAMM, we classified
all these variants into deleterious, damaging, or benign categories. Out of total
2,241 variants, 23 (1.02%) variants were extreme deleterious (rank 1), 70 (3.12%)
variants were deleterious (rank 2), and 1,937 (86.43%) variants were benign (rank
3). The results show 14% of lead or associated variants are under strong negative
selection (GERP++ RS >=2), and ~22% are under balancing selection (Tajima's D
score >2) in CEU population of 1KGP-the regions being positively selected (GERP++
RS <0) in mammalian evolution. The expression quantitative trait loci of highest
deleteriously ranked genes were tested on relevant adipose and breast tissues,
the results of which were extended for protein expression on breast tissues. From
the concordance analysis of ranking system of GWAVA, CADD, and FATHMM, eQTL and
protein expression, we identified the deleterious SNPs localized in STXBP4 and
ZNF404 genes which might play a role in BC development by dysregulating its gene
expression. This simple approach will be easier to implement and to prioritize
large scale GWAS data for variety of diseases and link to the potentially
unrecognized functional roles of genes. J. Cell. Biochem. 118: 4296-4307, 2017.
(c) 2017 Wiley Periodicals, Inc.
PMID- 28422316
TI - Regulatory T cells: tolerance induction in solid organ transplantation.
AB - The concept of regulatory T cell (Treg ) therapy in transplantation is now a
reality. Significant advances in science and technology have enabled us to
isolate human Tregs , expand them to clinically relevant numbers and infuse them
into human transplant recipients. With several Phase I/II trials under way
investigating Treg safety and efficacy it is now more crucial than ever to
understand their complex biology. However, our journey is by no means complete;
results from these trials will undoubtedly provoke both further knowledge and
enquiry which, alongside evolving science, will continue to drive the
optimization of Treg therapy in the pursuit of transplantation tolerance. In this
review we will summarize current knowledge of Treg biology, explore novel
technologies in the setting of Treg immunotherapy and address key prerequisites
surrounding the clinical application of Tregs in transplantation.
PMID- 28422319
TI - Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery.
AB - Exosomes, the natural vehicles of intercellular communication, transfer proteins,
mRNAs, and microRNAs (miRNAs) and mediate many physiological and pathological
processes. It is not clear that whether exosomal miRNAs could regulate gene
expression across species, though some studies suggest interactions of exosomal
miRNAs between cells. In this report, we have isolated exosomes from rat PC12
cells and assessed their internalization by human cancer Hela cells. The
internalized exosomes were located in Hela lysosomes. Human PTEN expression was
significantly deregulated due to miR-21 delivered by rat cell exosomes. Our
results prove that exosomes could incorporate between cells of different species
and could regulate the protein expressions in the recipient cells by delivering
the enclosed miRNAs. Thus our study foreshadows a futuristic treatment approach
of utilizing miRNA enclosed exosome vehicles sans species concerns in combating
various diseases/ regulating abnormal proteins. J. Cell. Biochem. 118: 4267-4274,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422320
TI - miR-34b Modulates Skeletal Muscle Cell Proliferation and Differentiation.
AB - Myogenesis involves myoblast proliferation and differentiation to myocytes,
followed by fusion and hypertrophy to form myotubes during muscle development.
Increasing evidence showed that microRNAs (miRNAs) play important roles in the
regulation of myogenesis. We have previously revealed that miR-34b is steadily
increased during this process. This miRNA regulates differentiation in various
cell types, though its function in myogenesis remains to be elucidated. In this
study, we show that miR-34b represses muscle cell proliferation and promotes
myotube formation. Our quantitative iTRAQ-based proteomic analysis reveals 97
proteins are regulated by miR-34b in mouse myoblast C2C12. We identified that miR
34b targets 14-3-3 protein gamma, adenosylhomocysteinase and nucleolin by binding
to their 3'UTR. Further analysis of these proteins expression patterns show that
nucleolin is a cognate target of miR-34b during myogenic differentiation. Here,
we proved that a moderate reduction of nucleolin in cells enhanced the myotube
formation. However, nucleolin is required for myogenesis, as cells with low
levels of nucleolin reduced cell proliferation rate and are unable to
differentiate. Our data demonstrated that nucleolin regulates myogenesis in a
protein-abundance-dependent manner. J. Cell. Biochem. 118: 4285-4295, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28422321
TI - Aberrantly Expressed Long Non-Coding RNAs In CD8+ T Cells Response to Active
Tuberculosis.
AB - Dysregulated expression of long noncoding RNAs (lncRNAs) has been demonstrated as
being implicated in a variety of human diseases. In the study we aimed to
determine lncRNA profile in CD8+ T cells response to active tuberculosis (TB). We
examined the lncRNA expression by microarray in circulating CD8+ T cells isolated
from patients with active TB and healthy controls. Change predictions to analysis
was used to address functional roles of the deregulated mRNAs. Real-time
quantitative PCR (RT-qPCR) was used to validate the microarray result. In total,
328 lncRNAs and 356 mRNAs were differentially expressed in TB CD8+ T cells.
Upregulated mRNAs were mainly enriched in cAMP signaling pathway, calcium
signaling pathway, and TGF-beta signaling pathway, while downregulated mRNAs were
enriched in antigen processing and presentation and natural killer cell mediated
cytotoxicity in TB CD8+ T cells. Interestingly, we found that heme oxygenase 1
(HMOX1) was decreased in active TB CD8+ T cells, while its nearby lincRNA
XLOC_014219 was upregulated. Subsequent RT-qPCR results confirmed the changes.
This is the first research addressing lncRNA expression profiles in active TB
CD8+ T cells. The aberrantly expressed lncRNAs observed in the study may provide
clues to the dysfunction of CD8+ T cells and so to the pathophysiological
properties of active TB. Further studies should focus on the function of lncRNAs
involved in active TB. J. Cell. Biochem. 118: 4275-4284, 2017. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28422323
TI - Validating a Virtual Environment for Sexual Assault Victims.
AB - Virtual reality has shown promising results in the treatment of posttraumatic
stress disorder (PTSD) for some traumatic experiences, but sexual assault has
been understudied. One important question to address is the relevance and safety
of a virtual environment (VE) allowing patients to be progressively exposed to a
sexual assault scenario. The aim of this study was to validate such a VE. Thirty
women (victims and nonvictims of sexual assault) were randomly assigned in a
counter-balanced order to 2 immersions in a virtual bar: a control scenario where
the encounter with the aggressor does not lead to sexual assault and an
experimental scenario where the participant is assaulted. Immersions were
conducted in a fully immersive 6-wall system. Questionnaires were administered
and psychophysiological measures were recorded. No adverse events were reported
during or after the immersions. Repeated-measures analyses of covariance revealed
a significant time effect and significantly more anxiety (Cohen's f = 0.41, large
effect size) and negative affect (Cohen's f = 0.35, medium effect size) in the
experimental scenario than in the control condition. Given the safety of the
scenario and its potential to induce emotions, it can be further tested to
document its usefulness with sexual assault victims who suffer from PTSD.
PMID- 28422322
TI - Pentraxin-3 modulates lipopolysaccharide-induced inflammatory response and
attenuates liver injury.
AB - : Acute-on-chronic liver injury is characterized by an important inflammatory
response frequently associated with endotoxemia. In this context, acute-phase
proteins such as Pentraxin-3 (PTX3) are released; however, little is known about
their role in chronic liver disease. The aim of this study was to elucidate the
role of PTX3 in liver injury. The role of PTX3 was evaluated in cultured human
cells, liver tissue slices, and mice with acute-on-chronic liver injury. PTX3
expression was assessed in tissue and serum samples from 54 patients with
alcoholic hepatitis. PTX3 expression was up-regulated in animal models of liver
injury and strongly induced by lipopolysaccharide (LPS). Liver cell fractionation
showed that macrophages and activated hepatic stellate cells were the main cell
types expressing PTX3 in liver injury. Ex vivo and in vivo studies showed that
PTX3 treatment attenuated LPS-induced liver injury, inflammation, and cell
recruitment. Mechanistically, PTX3 mediated the hepatic stellate cell wound
healing response. Moreover, PTX3 modulated LPS-induced inflammation in human
primary liver macrophages and peripheral monocytes by enhancing a TIR domain
containing adapter-inducing interferon-dependent response and favoring a
macrophage interleukin-10-like phenotype. Additionally, hepatic and plasma PTX3
levels were increased in patients with alcoholic hepatitis, a prototypic acute-on
chronic condition; and its expression correlated with disease severity scores,
endotoxemia, infections, and short-term mortality, thus suggesting that
expression of PTX3 found in patients could be a counterregulatory response to
injury. CONCLUSION: Experimental and human evidence suggests that, in addition to
being a potential biomarker for alcoholic hepatitis, PTX3 participates in the
wound-healing response and attenuates LPS-induced liver injury and inflammation;
therefore, administration of PTX3 could be a promising therapeutic strategy in
acute-on-chronic conditions, particularly those associated with endotoxemia.
(Hepatology 2017;66:953-968).
PMID- 28422324
TI - Optical resolution and mechanism using enantioselective cellulose, sodium
alginate and hydroxypropyl-beta-cyclodextrin membranes.
AB - Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-beta
cyclodextrin were prepared for chiral dialysis separations. After optimizing the
membrane material concentrations, the membrane preparation conditions and the
feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were
obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on
the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl
beta-cyclodextrin membrane, respectively. To study the optical resolution
mechanism, chiral discrimination by membrane adsorption, solid phase extraction,
membrane chromatography, high-pressure liquid chromatography ultrafiltration were
performed. All of the experimental results showed that the first adsorbed
enantiomer was not the enantiomer that first permeated the membrane. The crystal
structures of mandelic acid and p-hydroxy phenylglycine are the racematic
compounds. We suggest that the chiral separation mechanism of the solid membrane
is "adsorption - association - diffusion," which is able to explain the optical
resolution of the enantioselective membrane. This is also the first report in
which solid membranes of sodium alginate and hydroxypropyl-beta-cyclodextrin were
used in the chiral separation of p-hydroxy phenylglycine.
PMID- 28422325
TI - The way forward in addressing abusive head trauma in infants - current
perspectives from Sweden.
PMID- 28422326
TI - Alveolar ridge dimensional changes following ridge preservation procedure with
novel devices: part 3 - histological analysis in non-human primate model.
AB - OBJECTIVES: This study sought to investigate the histological changes following
tooth extraction, ridge preservation and augmentation, using novel devices
designed to obturate the oral orifice of extraction sockets (SocketKAPTM) and
provide structural support for sockets with defective bony walls (SocketKAGETM)
in a non-human primate model. MATERIAL AND METHODS: Six Macaca fascicularis were
imaged by cone beam computed tomography to register their preoperative alveolar
bone. Three teeth were extracted in each animal, yielding intact socket walls and
were divided into three intervention groups: unassisted healing negative control
(Group A); SocketKAPTM (Group B); filled with anorganic bovine bone mineral
(ABBM) + SocketKAPTM (Group C). Three additional teeth were extracted in each
animal, followed by surgical resection of the entire buccal alveolar bone and
divided into three groups: negative control (Group D); SocketKAPTM + SocketKAGETM
(Group E); ABBM + SocketKAPTM + SocketKAGETM (Group F). Animals were euthanized
after 12 weeks, and treatment sites were examined by histology and
histomorphometric analysis. RESULTS: Control sockets with unassisted healing
(Groups A and D) underwent severe loss of bone width, height and total area
(approximately 40-60% loss). Application of SocketKAPTM in sites with intact
walls, as well as SocketKAPTM plus SocketKAGETM in sites with defective buccal
walls lead to higher preservation of alveolar bone height after 12 weeks post
intervention. Addition of ABBM leads to the highest degree of alveolar bone
dimensional preservation. Control sites with unassisted healing (Groups A and D),
as well as sites treated with extraction socket devices (Groups B and E) without
ABBM yielded higher percentage of vital bone, compared with sites filled with
ABBM (Groups C and F). No adverse histological responses were noted to
SocketKAPTM or SocketKAGETM devices. CONCLUSIONS: SocketKAPTM + SocketKAGETM
devices proved effective in reducing post-extraction alveolar bone resorption
mediating favorable wound healing within sockets. Addition of ABBM was associated
with reduced volumetric loss, although the bone fill was characterized by less
mature as well as more woven bone.
PMID- 28422328
TI - Synthesis of Benzo[c]silole Derivatives Bearing a Tetrasubstituted Exocyclic C=C
Double Bond by Palladium-Catalyzed Domino Reactions.
AB - The synthesis of diversely substituted 2,3-dihydro-benzo[c]siloles through an
unprecedented palladium-catalyzed domino sequence is reported, involving a
cyclocarbopalladation of an internal silylalkyne. This reaction proceeds with
complete stereoselectivity to lead to a fully substituted exocyclic C=C double
bond. Notably, the overall domino sequence appears to be crucial to obtain the
desired cyclic vinylsilanes.
PMID- 28422327
TI - Association between the ulcer status and the risk of delayed bleeding after the
endoscopic mucosal resection of colon.
AB - BACKGROUND AND AIM: Bleeding is the most common adverse event following
colonoscopic endoscopic mucosal resection (EMR). We aimed to assess the clinical
outcomes of a colon EMR according to the post-EMR ulcer status and determine the
risk factors of delayed postpolypectomy bleeding (DPPB) based on the post-EMR
ulcer status. METHODS: The medical records and endoscopic images of patients who
underwent EMR of colon polyps with diameters of >= 5 mm were retrospectively
reviewed by us. If any exposed vessels were observed on the post-EMR ulcer, the
types of exposed vessels were classified into cut and uncut vessels. The
coagulation injuries on the post-EMR ulcer were categorized as grades 1, 2, or 3.
RESULTS: In total, 505 patients with 728 polyps were examined. Exposed vessels
were present in 416 post-EMR ulcers, including cut vessels in 11 (1.5%) and uncut
vessels in 405 (55.6%). With regard to coagulation injury, 113 (15.5%), 443
(60.9%), and 172 (23.6%) post-EMR ulcers had grades 1, 2, and 3 injuries,
respectively. DPPB was observed in 20 lesions (2.7%). Multivariate analysis
indicated that a polyp size > 10 mm (odds ratio [OR], 3.354; 95% confidence
interval [CI], 1.229-9.154), cut vessels (OR, 18.913; 95% CI, 3.106-115.187), and
grade 3 coagulation injury (OR, 16.796; 95% CI, 1.825-154.556) were associated
with DPPB. CONCLUSIONS: Cut vessels and severe coagulation injury on post-EMR
ulcers, as well as larger polyp size, are risk factors for DPPB. Careful
inspection of post-EMR ulcers and prophylactic hemostasis, if necessary, may
improve the clinical outcomes of colonoscopic EMR.
PMID- 28422329
TI - Metal Complexes of a Redox-Active [1]Phosphaferrocenophane: Structures,
Electrochemistry and Redox-Induced Catalysis.
AB - The synthesis and characterisation of several metal complexes of a redox-active,
mesityl(Mes)-substituted [1]phosphaferrocenophane, FcPMes (1), are reported.
Cyclic voltammetry studies on the bimetallic complexes [M(kappa1 P-1)(cod)Cl]
(M=Rh: 2; M=Ir: 4), [Rh(kappa1 P-1)2 (CO)Cl] (3) and [AuCl(kappa1 P-1)] (5), in
conjunction with DFT calculations, provided indications for a good electronic
communication between the metal atoms. To confirm that the ferrocenophane unit
might be able to electrochemically influence the reactivity of the coordinated
transition metal, the rhodium complex 2 was employed as stimuli-responsive
catalyst in the hydrosilylation of terminal alkynes. All reactions were greatly
accelerated with in situ generated 2+ as a catalyst as compared to 2. Even more
importantly, a markedly different selectivity was observed. Both factors were
attributed to different mechanisms operating for 2 and 2+ (alternative Chalk
Harrod and Chalk-Harrod mechanism, respectively). DFT calculations revealed
relatively large differences for the activation barriers for 2 and 2+ in the
reductive elimination step of the classical Chalk-Harrod mechanism. Thus, the key
to the understanding is a cooperative "oxidatively induced reductive elimination"
step, which facilitates both a higher activity and a markedly different
selectivity.
PMID- 28422330
TI - Genetic relationships among female fertility disorders, female fertility traits
and productivity of Holstein dairy cows in the early lactation period.
AB - Fertility health disorders from the early lactation period including retained
placenta (REPLA), metritis (MET), corpus luteum persistence (CLP),
anoestria/acyclia (AOEAC) and ovarial cysts (OC), as well as overall disease
categories (disorders during the postpartal period (DPP), ovary infertility
(OINF), overall trait definition "fertility disorders" (FD)), were used to
estimate genetic (co)variance components with female fertility and test-day
traits. The disease data set comprised 25,142 Holstein cows from parities 1, 2
and 3 resulting in 43,584 lactations. For disease traits, we used the binary
trait definition (sick or healthy) and disease count data reflecting the sum of
treatments for the same disease within lactation or within lactation periods.
Statistical modelling included single and multiple trait repeatability animal
models for all trait combinations within a Bayesian framework. Heritabilities for
binary disease traits ranged from 0.04 (OC) to 0.10 (REPLA) and were slightly
lower for the corresponding sum trait definitions. Correlations between both
trait definitions were almost one, for genetic as well as for permanent
environmental effects. Moderate to high genetic correlations were found among
puerperal disorders DPP, REPLA and MET (0.45-0.98) and among the ovarian
disorders OINF, AOEAC, CLP and OC (0.59-0.99). Genetic correlations between
puerperal and ovarian disorders were close to zero, apart from the REPLA-OC
association (0.55). With regard to fertility disorders and productivity in early
lactation, a pronounced genetic antagonistic relationship was only identified
between OC and protein yield. Genetic correlations between fertility disorders
and test-day SCS were close to zero. OINF and all diseases contributing to OINF
were strongly correlated with the female fertility traits "interval from calving
to first service," "interval from service to pregnancy" and "interval from
calving to pregnancy." The strong correlations imply that fertility disorders
could be included in genetic evaluations of economic fertility traits as
correlated predictors. Vice versa, a breeding focus on female fertility traits
will reduce genetic susceptibility to OC, CLP and AOEAC.
PMID- 28422331
TI - A Metal-Free Oxidative Dehydrogenative Diels-Alder Reaction for Selective
Functionalization of Alkylbenzenes.
AB - Functionalization of C(sp3 )-H bonds under metal-free reaction conditions is a
great challenge due to poor bond reactivity. A novel metal-free oxidative
dehydrogenative Diels-Alder reaction of alkylbenzene derivatives with alkenes
through C(sp3 )-H bond functionalization is described. The developed oxidative
method provides a straightforward approach to biologically relevant 1,4
phenanthraquinone and isoindole derivatives from readily available starting
materials. Furthermore, the synthesis of nitrostyrenes from enylbenzene
derivatives by selective C(sp3 )-H bond functionalization has been demonstrated.
PMID- 28422332
TI - Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria
with unique properties.
AB - In most environments, microorganisms evolve in a sessile mode of growth,
designated as biofilm, which is characterized by cells embedded in a self
produced extracellular matrix. Although a biofilm is commonly described as a
"cozy house" where resident bacteria are protected from aggression, bacteria are
able to break their biofilm bonds and escape to colonize new environments. This
regulated process is observed in a wide variety of species; it is referred to as
biofilm dispersal, and is triggered in response to various environmental and
biological signals. The first part of this review reports the main regulatory
mechanisms and effectors involved in biofilm dispersal. There is some evidence
that dispersal is a necessary step between the persistence of bacteria inside
biofilm and their dissemination. In the second part, an overview of the main
methods used so far to study the dispersal process and to harvest dispersed
bacteria was provided. Then focus was on the properties of the biofilm-dispersed
bacteria and the fundamental role of the dispersal process in pathogen
dissemination within a host organism. In light of the current body of knowledge,
it was suggested that dispersal acts as a potent means of disseminating bacteria
with enhanced colonization properties in the surrounding environment.
PMID- 28422333
TI - Assembling Porphyrins into Extended Network Structures by Employing Aromatic
Dicarboxylates: Synthesis, Metal Exchange, and Heterogeneous Catalytic Studies.
AB - Three new metal-organic porphyrinic framework compounds of zinc and 5,10,15,20
tetrakis(4-pyridyl)porphyrin (TPyP) have been synthesized under solvothermal
conditions. The compounds [Zn5 (C40 H24 N8 )(C8 H4 O4 )2 (NO3 )6 (DMA)2 ] (DMA)3
(H2 O)8 (1; DMA=dimethylacetamide), [Zn3 (C40 H24 N8 )(C8 H4 O4 )2 (DMF)](DMF)5
(H2 O)12 (2), and [Zn3 (C40 H24 N8 )(C12 H6 O4 )2 (DMA)2 ](H2 O)7 (3) have two
(1) and three dimensionally (2 and 3) extended structures. All the three
structures contain porphyrinic units connected through the carboxylate linkers.
The nitrates bind the metal centers and are not hydrogen bonded. The different
binding modes of nitrate in the structure of 1 are observed for the first time in
a porphyrin-based MOF. The openness of the structure allowed us to explore metal
exchange through a room-temperature metathetic route. Compound 2 undergoes 100 %
exchange with copper, whereas compound 3 exchanges 70 % with copper. The copper
exchanged compounds Cu?2 and Cu?3 were observed to be good heterogeneous
catalysts for many important organic reactions. The chemo and regioselective
enamination of beta-ketoesters, preparation of propargylamine derivatives as well
as regioselective cycloadditions of alkyne and azide (click reactions) have been
carried out with good yields and selectivity. All the compounds have been
characterized by PXRD, IR, UV/Vis, atomic absorption spectroscopy (AAS), and
energy-dispersive X-ray spectroscopy (for Cu exchange).
PMID- 28422334
TI - Polymer-Supported Palladium(II) Carbene Complexes: Catalytic Activity,
Recyclability, and Selectivity in C-H Acetoxylation of Arenes.
AB - Heterogeneous catalysts for selective oxidation of C-H bonds were synthesized by
co-polymerization of new N-heterocyclic carbene-palladium(II) (NHC-PdII )
monomers with divinylbenzene. The polymer-supported NHC-PdII -catalysed
undirected C-H acetoxylation of simple and methylated arenes as well as
polyarenes, with similar or superior efficiency compared to their homogeneous
analogues. In particular, the regioselectivity has been improved in the
acetoxylation of biphenyl and naphthalene compared to the best homogeneous
catalysts. The new polymer-supported catalysts maintain the original oxidation
state of PdII after repeated catalytic reactions, and exhibit no significant
leaching of palladium. In addition, the new catalysts have been successfully
recovered and reused without loss of activity over several cycles of reactions.
PMID- 28422335
TI - Effect of Isomeric Structures on Photovoltaic Performance of D-A Copolymers.
AB - Two donor-acceptor copolymers based on isomeric acceptor units, [7,7'
bithieno[2',3':4,5]thieno[2,3-d]thieno[3,2-b]pyridine]-5,5'(4H,4'H)-dione (BTTP)
and [2,2'-bithieno[2',3':4,5]thieno[2,3-d]thieno[3,2-b]pyridine]-5,5'(4H,4'H)
dione (iBTTP), are developed to study the effect of isomeric structures on
photovoltaic performance. Compared with PBDTBTTP, PBDTiBTTP possesses a smaller
bandgap for good light harvesting and a better pi-pi stacking for higher hole
mobility. PBDTiBTTP solar cells present balanced mobilities and good nanoscale
phase separation, giving a power conversion efficiency (PCE) of 6.51%, with
higher short-circuit current (Jsc ) and fill factor (FF).
PMID- 28422336
TI - A Designed ZnO@ZIF-8 Core-Shell Nanorod Film as a Gas Sensor with Excellent
Selectivity for H2 over CO.
AB - The development of H2 gas sensors is important for H2 production as a fuel. In
this work, a ZnO@ZIF-8 core-shell nanorod film is designed and synthesized as a
gas sensor through a facile solution deposition process. This film shows an
excellent selective response for H2 over CO. By fine-tuning the reaction
conditions, a ZnO@ZIF-8 core-shell structure with a thin, fine-grain, porous ZIF
8 shell is obtained. Owing to the facile H2 penetration through the ZIF-8 thin
shell (~110 nm) and the increased oxygen vacancies for the complex film, the
ZnO@ZIF-8 nanorod film shows a higher H2 sensitivity than a raw ZnO nanorod film.
More importantly, the ZnO@ZIF-8 nanorod film shows no response for CO at 200
degrees C. Because of the fine-grain confinement of the porous ZIF-8 shell (<140
nm), the molecular sieving effect is strengthened, which allows the effective
separation of H2 over CO. This work provides a promising strategy for the design
of high-performance H2 sensors.
PMID- 28422337
TI - In vivo validation of a novel algorithm for automatic premature ventricular
contractions recognition.
AB - INTRODUCTION: Template-matching algorithms are routinely used in the catheter
ablation of patients with premature ventricular contractions (PVCs). However,
systematic analysis of the accuracy and spatial resolution of such systems is
lacking. Therefore, the aim of this evaluation was to perform a systematic in
vivo validation of performance of a novel automated template-matching algorithm.
METHODS AND RESULTS: In a porcine model, paced beats simulating PVCs from
different origins were investigated. The ability to discriminate between sinus
rhythm and PVCs was tested by simulating PVCs using sequential pacing from
different cardiac chambers. The accuracy of the algorithm in correctly
classifying PVCs was reviewed by an independent investigator. In addition, the
spatial resolution of pace matching was evaluated by assessing the QRS morphology
discrimination at a distance of 0, 2, 4, and 6 mm of a simulated PVCs focus. The
specificity of the algorithm for recognizing simulated PVCs was 99.6% and the
sensitivity was 85.3%. There was a significant difference in the discrimination
metric discrimination metric (with 0% being a perfect match and 100% being no
correlation) between PVC origin (median 0%, interquartile range (IQR) 0-2%)
versus at 2 mm (5%, IQR 2-7%), 4 mm (16%, IQR 11-21%), and 6 mm (24%, IQR 19-28%,
P < 0.001 for all). The c-statistic for discrimination between PVC origin and a
distance >= 2 mm was 0.93. CONCLUSIONS: Automated template matching had high
specificity and sensitivity, with good spatial discrimination and a pace-mapping
resolution in range of 2 mm. Clinical application of this algorithm may assist in
the interventional treatment of patients with PVCs.
PMID- 28422338
TI - Arene-Inserted Extended Germa[n]pericyclynes: Synthesis, Structure, and
Phosphorescence Properties.
AB - This report describes the synthesis and characterization of arene-inserted
extended (ArEx) germa[n]pericyclynes composed of germanium and 1,4
diethynylbenzene units. These novel cyclic germanium-pi unit materials were
synthesized with diethynylbenzene and germanium dichloride. X-ray
crystallographic analysis revealed their structures, and the planar conformation
of ArEx germa[4]pericyclyne along with the regular aromatic rings. UV/Vis
absorption spectra and fluorescence emission spectra showed considerably unique
and highly improved character compared to previously reported
germa[n]pericyclynes. Even in the absence of transition metal components,
phosphorescence emissions were observed, and the emission lifetimes were
dramatically improved. ArEx germa[n]pericyclynes showed high photoluminescence
quantum yields, whereas low photoluminescence quantum yields were observed for
acyclic compounds. Density functional theory calculations show delocalized
orbitals between skipped alkyne units through a germanium tether, and an increase
in the HOMO energy level, leading to a small HOMO-LUMO energy gap.
PMID- 28422339
TI - Prenatal exposure to beta2-adrenoreceptor agonists and the risk of autism
spectrum disorders in offspring.
AB - PURPOSE: We aimed to examine the risk of autism spectrum disorders (ASDs) in the
offspring who were exposed to maternal use of beta2-adrenoreceptor agonist
(beta2AA) during pregnancy. METHODS: This is a population-based cohort study
including all live singleton births in Denmark from 1 January 1997 to 31 December
2008. Children born to mothers who used beta2AA during pregnancy were categorized
as exposed, and all other children were included in the unexposed group. Cases of
ASDs were identified from the Danish Psychiatric Central Register and the Danish
Patient Register. Incidence rate ratio (IRR) and 95% confidence interval were
estimated by Poisson regression models. RESULTS: Among 751 888 children in the
cohort, 9098 (1.21%) received a diagnosis of ASDs. We observed an increased risk
of ASDs in the exposed children (IRR = 1.28, 1.11-1.47), especially for those who
were exposed during the second trimester period (IRR = 1.38, 1.14-1.67). However,
when extending the exposure time window to 1 year prior to pregnancy, we observed
a similar association in children born to women who received beta2AA treatment
during pregnancy (IRR = 1.33, 1.11-1.59) to that in children born to women who
received beta2AA treatment 1 year prior to pregnancy (IRR = 1.35, 1.17-1.56).
CONCLUSION: Our finding suggested that children born to women who used beta2AA
during pregnancy have an increased risk of ASDs in later life, which is more
likely due to underlying maternal diseases rather than the exposure to beta2AA
itself. However, further study, which would better differentiate the effects
between indication and medicine, is needed to corroborate the finding. Copyright
(c) 2017 John Wiley & Sons, Ltd.
PMID- 28422340
TI - Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium
Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total
Synthesis.
AB - Four new macrolactones, leptolyngbyolides A-D, were isolated from the
cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar
structures of leptolyngbyolides were determined by extensive NMR studies,
although complete assignment of the absolute configuration awaited the catalytic
asymmetric total synthesis of leptolyngbyolide C. The synthesis took advantage of
the catalytic asymmetric thioamide-aldol reaction using copper(I) complexed with
a chiral bidentate phosphine ligand to regulate two key stereochemistries of the
molecule at the outset. The present total synthesis demonstrates the utility of
this reaction for the construction of complex chemical entities. In addition to
the total synthesis, this work reports that leptolyngbyolides depolymerize
filamentous actin (F-actin) both in vitro and in cells. Detailed biological
studies suggest the probable order of F-actin depolymerization and apoptosis
caused by leptolyngbyolides.
PMID- 28422341
TI - Late pubertal growth spurt in a girl with growth hormone deficiency: Is Kaufmann
therapy effective in a girl with short stature who responds poorly to growth
hormone therapy and estrogen-replacement therapy?
AB - A Japanese senior high school girl aged 18 years and 5 months with growth hormone
deficiency was referred for primary amenorrhea. Her height was 1.36 m, and her
bodyweight was 23.5 kg. She had received daily growth hormone therapy from the
age of 5 years. Growth hormone therapy was discontinued at the age of 16 years
and 11 months, and estrogen-replacement therapy (ERT) was started to stimulate
secondary sexual characteristics. Although ERT was performed until the age of 18
years and 11 months, genital bleeding did not occur. ERT was changed to Kaufmann
therapy, and the first genital bleeding occurred 1 year and 4 months later.
Finally, regular medically induced menses occurred at the age of 21 years and 10
months. Her height increased by 9 cm in 1 year after the initiation of menstrual
bleeding. Kaufmann therapy was associated not only with menstrual bleeding but
also with growth spurt.
PMID- 28422342
TI - The Development of Lingualized Occlusion.
AB - This article is a historical review of the development of the lingualized
occlusion concept over the past century. It focuses on the pioneers of
lingualized occlusion and their designs rather than on techniques for achieving a
lingualized complete denture occlusion.
PMID- 28422343
TI - E-MALDI: optimized conditions during electrowetting-enhanced drop drying for
MALDI-MS.
AB - We recently showed that electrowetting-enhanced sample preparation for MALDI-MS
(eMALDI) can increase the intensity of the MALDI signal by 2-25 times compared
with conventional drop drying by concentrating all the dried sample in a single
spot rather than leaving behind a heterogeneous coffee-stain pattern. Here, we
demonstrate that the eMALDI signal enhancement can be further increased to more
than 100 times by systematically optimizing the electrowetting actuation
frequency and amplitude. This enables 30 times signal increase for a peptide
standard. Simultaneously, drop drying times can be reduced approximately five
times by increasing the actuation voltage and/or decreasing the initial drop
volume. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28422344
TI - Use of blood pool agents with steady-state MRI to assess the vascular system.
AB - : Over the past two decades there have been significant advances in the use of
magnetic resonance imaging (MRI) to assess the vascular system. New imaging
sequences and improvements in magnet design have enabled the creation of higher
spatial resolution images. MRI is now a viable alternative imaging modality when
compared to both invasive angiography and computed tomographic angiography. The
use of blood pool agents has further facilitated the use of MR angiography (MRA);
their high molecular weight allows for lower doses of contrast medium
administration while their prolonged presence in the blood stream allows for
repeated high-quality volumetric imaging of both the arterial and venous
circulation. As such, MRA is now no longer constrained by the tight windows for
first-pass arterial and venous enhancement, which has resulted in the ability to
assess and diagnose a large range of vascular pathologies in both arterial and
venous systems. The intent of this review is to highlight MRI findings in common
vascular pathologies including peripheral arterial disease (PAD), abnormalities
of the abdominal aortic branches, postendovascular aortic aneurysm repair (EVAR)
endoleak assessment, popliteal artery entrapment syndrome (PAES), deep venous
thrombosis (DVT), vascular thoracic outlet syndrome (TOS), and vascular
malformations. In addition, the latest MRI techniques currently used to optimally
assess each of these pathologies will be discussed. LEVEL OF EVIDENCE: 5
Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1559-1572.
PMID- 28422345
TI - Therapeutic Efficacy of Twin-Block and Fixed Oral Appliances in Patients with
Obstructive Sleep Apnea Syndrome.
AB - PURPOSE: To compare the efficacy of twin-block (i.e., allows mouth opening) and
fixed (i.e., maintains mouth closure) mandibular advancement splints (MASs) for
the treatment of obstructive sleep apnea-hypopnea syndrome (OSA). MATERIALS AND
METHODS: From 2011 to 2013, 23 patients with OSA in the twin-block group, and
from 2013 to 2015, 29 patients in the fixed MAS group were included. All patients
underwent polysomnography before and after 3 months of treatment. The two sets of
polysomnographic and cephalometric variables were compared. RESULTS: A
significant difference (p < 0.001) was observed in the apnea-hypopnea index
before and after MAS treatment in both groups (twin-block group: 20.6 +/- 11.5
vs. 14.7 +/- 9.4; fixed group: 21.4 +/- 15.2 vs. 11.2 +/- 9.7). In the twin-block
group, 5 patients (21.7%) were complete responders, 9 (39.1%) were fair
responders, and 9 (39.1%) were nonresponders; the corresponding figures for the
fixed group were 14 (48.3%), 9 (31.0%), and 6 (20.7%) patients. A significant
between-group difference was observed in the distribution of responders (p =
0.046). The fixed group showed a significant improvement in the snoring index (p
= 0.003), arousal index (p = 0.036), and desaturation rate (p = 0.012). Finally,
the change in incisal overjet was larger in the fixed group than in the twin
block group (p < 0.001). CONCLUSIONS: These results suggest that fixed oral
appliances are superior in treating OSA, based on their ability to prevent mouth
opening and reduce incisal overjet.
PMID- 28422346
TI - Does limb partitioning and positioning affect acute cardiorespiratory responses
during strength exercises in patients with COPD?
AB - BACKGROUND AND OBJECTIVE: Cardiorespiratory responses and symptoms in response to
endurance exercise in patients with COPD vary with the number and position of
involved limbs. Responses to such variations have never been quantified for
strength exercises. We therefore assessed acute cardiorespiratory responses
during brief bouts of weight lifting exercises. METHODS: We compared double-
versus single-limb leg extensions and arm elevations, as well as arm elevation
done above or below shoulder level in patients with moderate to severe COPD (n =
10, 6 males, 66 (8.1 years), forced expiratory volume on 1 s (FEV1 ) % predicted
= 34% (14%)). Minute ventilation, oxygen uptake, oxygen saturation, heart rate
(HR), blood pressure (BP), rate of perceived exertion (RPE) and recovery time
were collected during single sets of each exercise (10 repetitions at 80% of one
repetition maximum). RESULTS: Ventilatory and gas exchange responses were not
affected by the number of exercising limbs. Changes in HR, BP and RPE scores
during arm elevation above shoulder level were greater after double- compared
with single-arm elevation (P <= 0.001) and greater when exercising above compared
with below shoulder level (P <= 0.01). Double-arm elevation above shoulder level
required 1.5 min longer HR recovery time (P <= 0.041) compared with other
exercises. CONCLUSION: Double-arm elevation above shoulder level appears to be
more challenging than other strength exercise variations. Partitioning exercises
and limb position may reduce perceived exertion during training.
PMID- 28422347
TI - Serum placental growth factor and soluble fms-like tyrosine kinase 1 at mid
gestation in healthy women: Association with small-for-gestational-age neonates.
AB - AIM: This study was performed to determine the associations between serum
placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1)
levels at mid-gestation with the risk of small-for-gestational-age (SGA) neonates
born at gestational week (GW) >= 36 in healthy women. METHODS: PlGF and sFlt-1
concentrations were determined at GW 24-27 in 183 women with births at GW >= 36,
but without gestational diabetes mellitus and hypertension. RESULTS: Thirteen
(7.1%) SGA neonates were born. Median (range) GW at blood sampling was similar
between women with and without SGA (25 [24-25] and 24 [24-27], respectively, P =
0.671). Pre-pregnancy body mass index (BMI) and PlGF levels were significantly
lower in women with than without SGA, while sFlt-1 levels and sFlt-1 : PlGF ratio
(sFlt-1/PlGF) did not differ significantly between the two groups. PlGF and sFlt
1/PlGF, but not BMI or sFlt-1, showed significant correlations with birthweight z
score; the correlation was positive for PlGF and negative for sFlt-1/PlGF. Women
with PlGF level < 10th percentile and those with sFlt-1/PlGF level > 90th
percentile showed significantly increased risk of SGA compared to those with
respective counterpart characteristics; relative risk was 3.8 (95% confidence
interval, 1.3-11.3; 21% [4/19] vs 5.5% [9/164]) for PlGF and 7.9 (95% confidence
interval, 3.0-20.8, 33.3% [6/18] vs 4.2% [7/165]) for sFlt-1/PlGF. CONCLUSION:
Maternal PlGF and sFlt-1/PlGF determined during GW 24-27 were associated with the
risk of SGA neonates born at GW >= 36, even in women with uncomplicated
pregnancies.
PMID- 28422348
TI - Para-Hisian pacing maneuver: A pitfall in the pitfall.
PMID- 28422349
TI - Effects of extrinsic cardiac nerve stimulation on atrial fibrillation
inducibility: The regulatory role of the spinal cord.
AB - OBJECTIVE: To investigate the effect of the mutual regulation of the extrinsic
cardiac nerves on atrial electrophysiology and atrial fibrillation (AF)
vulnerability. METHODS AND RESULTS: Fourteen dogs were randomly divided into two
groups: spinal cord stimulation (SCS) group (n = 7) and spinal cord block (SCB)
group (n = 7). SCS was performed with 90% of the threshold voltage stimulating
the T1 -T2 spinal level, while SCB was performed by injecting 2% lidocaine into
the epidural space at the T2-3 level. The effective refractory period (ERP), ERP
dispersion, and AF inducibility were measured during atrial pacing combined with
different extrinsic cardiac nerve stimulation. ERPs were decreased in the atrium
and pulmonary veins and ERP dispersion was increased from baseline during left
cervical vagus nerve stimulation (VNS) or left stellate ganglion stimulation
(SGS) in the two groups. When combined with SCS, VNS resulted in diminished ERPs
at all recording sites, longer ERP dispersion and more episodes of AF than were
observed during VNS, whereas ERPs were greater and correspondingly fewer episodes
of AF occurred during SCS combined with SGS than SGS. In the SCB group, ERPs were
shortened, ERP dispersion was lengthened, and episodes of AF were increased
during SGS after SCB. SCS enhanced the activity of the left vagus nerve but
attenuated the left stellate ganglion and superior left ganglionated plexus.
CONCLUSION: SCS modulates extrinsic and intrinsic cardiac nerve activity among
the vagus nerve, stellate ganglion, and ganglionated plexus. SCS facilitates the
effect of VNS and attenuates the effect of SGS on atrial electrophysiology.
PMID- 28422350
TI - Electronic g Tensors in UV Complexes-A Computational Study.
AB - The theory and computation of EPR parameters from first principles has seen a
great deal of development over the past two decades. In particular, various
techniques for the computation of the electronic g tensor have been implemented
in many quantum chemistry packages. These methods have been successfully applied
to paramagnetic organic species and transition metal systems. The situation is
less well-understood and established in the case of actinide-containing molecules
and there is a dearth of experimental data available for validation of
computations. In this study quantum chemical techniques have been used to
evaluate the g tensor for UV complexes, for which experimental data are available
for comparison. The g tensors were calculated using relatively simple, state
averaged complete active space self-consistent field (SA-CASSCF) calculations.
This approach is shown to be capable of providing useful accuracy. Aspects of the
computations that should be refined to provide a more quantitative approach are
discussed. The key features of the underlying electronic structure that influence
the computed g values are delineated, providing a simple physical picture of
these subtle molecular properties.
PMID- 28422351
TI - Clinical phenotypes in asthma during childhood.
AB - Asthma is a heterogeneous disease characterized by numerous phenotypes relating
to age of onset, triggers, comorbidities, severity (assessed by multiple
exacerbations, lung function pattern) and finally the inflammatory cells involved
in the pathophysiologic pathway. These phenotypes can vary over time in relation
to changes in the principal triggers involved in the aetiology of the disease.
Nevertheless, in a patient with multiple allergies and early-onset disease
(defined as multiple sensitizations and allergic comorbidities), the prognosis of
asthma is poor with a high risk of persistence and severity of the disease during
childhood. Future research will focus on classifying phenotypes into groups based
on pathophysiologic mechanisms (endotypes) and the biomarkers attached to these
endotypes, which could predict prognosis and lead to targeted therapy. Currently,
these biomarkers are related to inflammatory cells associated with the asthma
endotype, essentially eosinophils and neutrophils (and related cytokines)
attached to Th-2 and non Th-1 pathways, respectively. The most severe asthma
(refractory asthma) is linked to neutrophil-derived inflammation (frequently
associated with female sex, obesity and possibly disorganized airway microbiota)
encountered in very young children or teenagers. Severe asthma is also linked to
or a marked eosinophil inflammatory process (frequently associated with multiple
atopy and, more rarely, with non-atopic hypereosinophilic asthma in children) and
frequently encountered in teenagers. Severe phenotypes of asthma could also play
a role in the origin of chronic obstructive pulmonary disease in adult life.
PMID- 28422353
TI - Comprehensive Review and Comparison of the Disinfection Techniques Currently
Available in the Literature.
AB - The goal of disinfection in the dental office is to prevent the spread of
infection from one patient to another and maintain the safety of the dental care
providers. Prevention of cross infection has significant effect on infection
control. The standard procedure of rinsing impressions under tap water
immediately after removal from the mouth eliminates microorganisms along with
saliva and blood. A broad search on published literature was done using the
keywords impression materials, disinfection method, and sterilization of dental
impression from 1980 to 2016 in Medline, Google Scholar, the internet, and
textbooks. This article critically analyzes the various published methods of
dental impression disinfection in dentistry.
PMID- 28422352
TI - Places and social contexts associated with simultaneous use of alcohol, tobacco
and marijuana among young adults.
AB - INTRODUCTION AND AIMS: Little is known about social-ecological correlates of
simultaneous use of alcohol with other substances. This study examined places and
social contexts associated with simultaneous use of alcohol, tobacco and
marijuana among young adults. DESIGN AND METHODS: We used survey data obtained
from 1538 young adult recent alcohol drinkers (49% male; 18-30 years old) in 24
non-contiguous cities in California. Event-level measures included alcohol,
tobacco and marijuana use, drinking places and social characteristics of the
event. Individual-level measures included alcohol expectancies, depression and
demographics. RESULTS: Bars and restaurants had less alcohol and marijuana use
(odds ratio = 0.34; 95% confidence interval 0.18, 0.62; P < 0.001) and alcohol,
marijuana and tobacco use (odds ratio = 0.27; 95% confidence interval 0.14, 0.54;
P < 0.001) compared with alcohol use only. Perceived percent of intoxicated
people at an event was associated with greater likelihood of using alcohol with
tobacco and marijuana at the event. At the individual level, greater age was
generally associated with increased odds of simultaneous use. Participants who
were male, less educated, more depressed and had positive alcohol expectancies
were more likely to simultaneously co-use alcohol with tobacco and marijuana.
Those with negative expectancies were less likely to simultaneously use these
substances. DISCUSSION AND CONCLUSIONS: Social events in private settings with a
high percentage of people who are intoxicated had increased likelihood of
simultaneous use of alcohol, tobacco and marijuana. Prevention efforts in these
settings may reduce simultaneous use of these substances and related harms.
[Lipperman-Kreda S, Paschall MJ, Saltz RF, Morrison CN. Places and social
contexts associated with simultaneous use of alcohol, tobacco and marijuana among
young adults. Drug Alcohol Rev 2017;00:000-000].
PMID- 28422354
TI - Auditory Verbal Experience and Agency in Waking, Sleep Onset, REM, and Non-REM
Sleep.
AB - We present one of the first quantitative studies on auditory verbal experiences
("hearing voices") and auditory verbal agency (inner speech, and specifically
"talking to (imaginary) voices or characters") in healthy participants across
states of consciousness. Tools of quantitative linguistic analysis were used to
measure participants' implicit knowledge of auditory verbal experiences (VE) and
auditory verbal agencies (VA), displayed in mentation reports from four different
states. Analysis was conducted on a total of 569 mentation reports from rapid eye
movement (REM) sleep, non-REM sleep, sleep onset, and waking. Physiology was
controlled with the nightcap sleep-wake mentation monitoring system. Sleep-onset
hallucinations, traditionally at the focus of scientific attention on auditory
verbal hallucinations, showed the lowest degree of VE and VA, whereas REM sleep
showed the highest degrees. Degrees of different linguistic-pragmatic aspects of
VE and VA likewise depend on the physiological states. The quantity and
pragmatics of VE and VA are a function of the physiologically distinct state of
consciousness in which they are conceived.
PMID- 28422355
TI - New insights into the morphogenesis of the gubernaculum testis and the inguinal
canal.
AB - There is no consensus about the role of the gubernaculum testis (GT). Nineteen
human embryos (Carnegie stages 15-23), 36 fetuses (9 weeks to term), and eight
neonates were examined. All the embryos and 25 fetuses (from weeks 9-16) were
processed for paraffin wax histology and serially sectioned at 10 um thickness.
The remaining 11 fetuses and the eight neonates were fresh specimens that were
dissected under a surgical microscope. The GT appeared during the embryonic
period (stages 17-23) with a horseshoe-shaped mesenchyme condensation of the
superior concavity, which was observed in four different topographical regions
sequentially through development. The GT was not attached at either of its ends
in any of the specimens, not to the gonad or in the scrotal sac. The inguinal
canal differentiates around the inguinal portion of the GT during the late
embryonic period. After stage 21, the GT appears enveloped by an evagination of
the peritoneal cavity. It has few striate muscular fibers and vessels. Although
the GT does not appear to have the role traditionally attributed to it, it is
still an essential structure and indirectly facilitates the descent of the
testes. It contributes to the formation of the inguinal canal and then forges the
pathway that the testes will subsequently take through the inguinal canal as they
migrate from the abdominal cavity into the scrotal sac. Clin. Anat. 30:599-607,
2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422356
TI - Bilateral femoral neck fractures resulting from pregnancy-associated osteoporosis
showed bone marrow edema on magnetic resonance imaging.
AB - Femoral neck fractures resulting from pregnancy-associated osteoporosis is a rare
condition. Herein, we report an undoubted case of pregnancy-associated
osteoporosis in a 38-year-old primiparous patient with pre-existing anorexia
nervosa who suffered bilateral femoral neck fractures in the third trimester and
early post-partum period. Magnetic resonance imaging revealed femoral neck
fractures as well as diffuse marrow edema involving both femoral heads, which are
considered under ordinary circumstances as characteristic imaging findings of
transient osteoporosis of the hip. Based on our experience, we propose that
pregnancy-associated osteoporosis might be present in femoral neck fractures
attributed to transient osteoporosis of the hip in pregnancy. Conversely, bone
status should be carefully and accurately estimated in cases of potential
transient osteoporosis of the hip in pregnancy to reduce future fracture risk.
PMID- 28422357
TI - Comparative analysis of the merino sheep and Iberian red deer abomasum during
prenatal development.
AB - The aim of this study is to describe differences in the ontogenesis of the
abomasum in sheep (domestic ruminant) and deer (wild ruminant). Histomorphometric
and immunohistochemical analysis were carried out on 50 embryos and fetuses of
the sheep and 50 red deer from the first prenatal stages until birth. To compare
similar periods of gestation in both species, we calculate the percentages of
gestation. The appearance of the abomasum was earlier in the red deer (22%
gestation) than in the sheep (25% gestation). Throughout development the
epithelium happened sequentially, being of the types pseudostratified to simple
cylindrical. This important modification was earlier in the red deer than the
sheep. At 46% gestation in red deer and 50% in sheep, gastric pits were observed
on the surface of abomasal folds. Our studies suggest a close link between the
initial formation of these pseudoglandular structures and the clear separation of
lamina propria and submucosa separated by de muscularis mucosae. At 54% gestation
in red deer and at 60% in sheep, in the bottom of these pits the first outlines
of glands were distinguishable. Finally, the presence of neuroendocrine and glial
cells were detected in deer at earlier stages than in sheep.
PMID- 28422358
TI - Is mean platelet volume a better biomarker in pre-eclampsia?
AB - AIM: Platelet activation and destruction is a well recognized feature of pre
eclampsia, but the current literature is contradictory regarding the role of mean
platelet volume (MPV) in the diagnosis of this condition. We investigated whether
MPV, compared with other routine laboratory markers such as platelet count, is a
more significant biomarker of pre-eclampsia, giving special attention to the
intrapartum period. METHODS: Biochemical and hematological markers along
pregnancy including MPV were compared retrospectively between pre-eclampsia and
matched controls. Laboratory marker data were compared using independent t-test.
A logistic regression model was used to compare the strength of the associations
of MPV and other routine markers such as platelet count with pre-eclampsia.
Receiver operating characteristic curves were plotted. RESULTS: There were a
total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group,
there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of
eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the
control group (11.3 +/- 1.0 vs 10.1 +/- 0.8 fL, P = 0.002). On multivariate
analysis, MPV was the only statistically significant biomarker of pre-eclampsia
(OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6);
performing superiorly to platelet count. CONCLUSIONS: Mean platelet volume is a
more significant biomarker of pre-eclampsia. It is more significantly associated
with this condition than other routinely measured laboratory markers such as
platelet count. MPV is routinely obtained on complete blood cell count and its
utilization in the assessment of pre-eclampsia in a clinical setting should
continue to be evaluated.
PMID- 28422359
TI - Clinical Evaluation of Indirect Particle-Filled Composite Resin CAD/CAM Partial
Crowns after 24 Months.
AB - PURPOSE: Resin-based CAD/CAM compound materials might be promising for single
tooth restorations. Insufficient clinical data are available for this new
material class. The purpose of this study was to describe initial clinical in
vivo results for indirect particle-filled composite resin CAD/CAM restorations
after 24 months. MATERIALS AND METHODS: Indirect particle-filled composite resin
restorations were fabricated with a CAD/CAM method (CEREC Bluecam intraoral
scanner, CEREC MCXL milling unit) by calibrated dental students. Forty-two
partial crown restorations were seated adhesively in 30 patients with caries
lesions or insufficient restorations (baseline). Strict inclusion criteria were
defined for the patient collective. Follow-up evaluation comprised 40
restorations after 12 months and 33 restorations after 24 months. Evaluation
criteria were modified FDI criteria with grades (1) to (5). Rating with FDI
criteria (5) was defined as clinical failure. Statistical analysis was performed
with Wilcoxon-Test (p < 0.05). RESULTS: The success rate of indirect particle
filled composite resin CAD/CAM restorations after 12 months was 95.0% with two
debondings observed. The cumulative success rate for indirect particle-filled
composite resin CAD/CAM restorations after 24 months was 85.7% with two tooth
fractures and one debonding. Statistically significant differences were found for
baseline and 24-month follow-up evaluation for anatomic form and marginal
adaptation criterion examined in respect to FDI criteria guidelines (Wilcoxon
Test, p < 0.05). CONCLUSIONS: This study demonstrates particle-filled composite
resin CAD/CAM restorations having a clinical success rate of 85.7% after 24
months. Adhesive bonding procedures need to be ensured carefully. A longer
clinical evaluation period is necessary to draw further conclusions.
PMID- 28422360
TI - Photoinduced Iron-Based Water-Induced Phase Separable Catalysis (WPSC) ICAR ATRP
of Poly(ethylene glycol) Methyl Ether Methacrylate.
AB - Iron-mediated atom transfer radical polymerization (ATRP) has gained extensive
attention because of the superiority of iron catalysts, such as low toxicity,
abundant reserves, and good biocompatibility. Herein, a practical iron catalyst
recycling system, photoinduced iron-based water-induced phase separable catalysis
ATRP with initiators for continuous activator regeneration, at room temperature
is developed for the first time. In this polymerization system, the
polymerization is conducted in homogenous solvents consisting of p-xylene and
ethanol, using commercially available 5,10,15,20-tetraphenyl-21H,23H-porphine
iron(III) chloride as the iron catalyst, ethyl 2-bromophenylacetate as the ATRP
initiator, 2,4,6-trimethylbenzoyl diphenylphosphine oxide as the photoinitiator,
and poly(ethylene glycol) methyl ether methacrylate as the model hydrophilic
monomer. After polymerization, a certain amount of water is added to induce the
phase separation so that the catalyst can be separated and recycled in p-xylene
phase with very low residual metal complexes (<12 ppm) in the resultant polymers
even after six times recycle experiments.
PMID- 28422361
TI - Risks of thromboembolism associated with hormone contraceptives in Japanese
compared with Western women.
AB - We extracted 581 thromboembolic events associated with combined oral
contraceptives (COC) that occurred between 2004 and 2013 in Japan, from the
Pharmaceuticals and Medical Devices Agency database. The most common
thromboembolic events associated with COC were deep vein thrombosis, pulmonary
embolism and their combination. The reported thromboembolic events increased year
by year, in association with an increase in the quantity of prescribed low-dose
estrogen progestin after approval for health insurance coverage for dysmenorrhea
in 2008 in Japan. The incidence of venous thromboembolism (VTE) in Japanese COC
users is estimated to be lower compared with their Western counterparts. In
contrast, the frequency of all thromboembolic events peaked at 90 days from the
start of COC, as in Western studies. The risk of VTE in the overweight group
(body mass index >= 25 kg/m2 ) was more than twofold higher than in the standard
group, and age-specific incidence rate rose sharply after the age of 40. There
were different VTE risks according to progestin type in Japan as in Western
countries, but a definite conclusion about risk according to progestin type was
not able to be reached at present. As for the risk of arterial embolism and
thrombosis, the difference by progestin type was small, but it became higher at
>=50 years of age. Last, mortality rate caused by thromboembolism is extremely
low among COC users.
PMID- 28422362
TI - Ultrasound diagnosis of intramural pregnancy.
AB - Intramural pregnancy is a rare type of ectopic pregnancy, where the gestational
sac is implanted inside the myometrium instead of the endometrial and fallopian
tubes. Preoperative diagnosis remains very difficult. Ultrasonic findings vary
according to the anatomical location or duration of pregnancy. In this study, we
summarized the ultrasonic characteristics of intramural pregnancy by assessing
three cases. We also propose a set of ultrasonic characteristics to facilitate
differential diagnosis between intramural pregnancy and other types of ectopic
pregnancy.
PMID- 28422363
TI - The occhiolino (occ) mutant Zebrafish, a model for development of the optical
function in the biological lens.
AB - BACKGROUND: Zebrafish visual function depends on quality optics. An F3 screen for
developmental mutations in the Zebrafish nervous system was conducted in wild
type (wt) AB Zebrafish exposed to 3 mM of N-ethyl-N-nitrosourea (ENU). RESULTS:
Mutant offspring, identified in an F3 screen, were characterized by a small
pupil, resulting from retinal hypertrophy or hyperplasia and a small lens.
Deficits in visual function made feeding difficult after hatching at
approximately 5-6 days postfertilization (dpf). Special feeding conditions were
necessary for survival of the occhiolino (occ) mutants after 6 dpf. Optokinetic
response (OKR) tests measured defects in visual function in the occ mutant,
although electroretinograms (ERGs) were normal in the mutant and wt. Consistent
with the ERGs, histology found normal retinal structure in the occ mutant and wt
Zebrafish. However, lens development was abnormal. Multiphoton imaging of the
developmental stages of live embryos confirmed the formation of a secondary mass
of lens cells in the developing eye of the mutant Zebrafish at 3-4 dpf, and
laminin immunohistochemistry indicated the lens capsule was thin and disorganized
in the mutant Zebrafish. CONCLUSIONS: The occ Zebrafish is a novel disease model
for visual defects associated with abnormal lens development. Developmental
Dynamics 246:915-924, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422364
TI - Novel technique for adhesion barrier insertion by using cut-off surgical glove
fingers in laparoscopic surgery.
AB - AIM: Laparoscopic surgery causes fewer postoperative adhesions than laparotomy
and adhesion barriers are used to lessen the chance of adhesion. Sodium
hyaluronate and carboxymethylcellulose (SH-CMC), a bioresorbable membrane, is
effective in preventing adhesions. However, its properties make it difficult to
insert the film into the abdominal cavity and to place it into the target area
during laparoscopic surgeries. Here we report a novel technique for applying SH
CMC during laparoscopic surgeries by using cut-off surgical glove fingers.
METHODS: In our dry-box experiment, we found that SH-CMC became more flexible
after moisturizing for 30 s. Therefore, for this procedure, we moisturizing both
sides of the SH-CMC sheet (7.35 * 6.35 cm) on wet gauze (for 30 s). The film was
rolled into cut-off surgical glove fingers and inserted into the abdominal cavity
through a 12-mm trocar. The film was then removed from the glove finger and
unrolled onto the target area (glove-finger method). RESULTS: The dry-box
experiment revealed that moisturizing both sides of SH-CMC for 30 s/side, 15 min
after package removal, made the film more flexible. Ninety of 96 attempts with SH
CMC were successful among the 24 patients who underwent total laparoscopic
hysterectomy with our glove-finger method. CONCLUSION: Our glove-finger method
can realize the smooth application of SH-CMC to the target area during
laparoscopic surgeries.
PMID- 28422365
TI - Successful vaginal delivery at term after vaginal reconstruction with labium
minus flaps in a patient with vaginal atresia: A rare case report.
AB - We report a case of successful vaginal delivery after vaginal reconstruction with
labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The
patient primarily presented with amenorrhea and cyclic abdominal pain;
transabdominal ultrasonography revealed an enlarged uterus due to hematometra and
absence of the lower segment of the vagina. Eight years ago, she had undergone an
unsuccessful attempt at canalization at a local hospital. Upon referral to our
hospital, she underwent vaginal reconstruction with labium minus flaps. Four
months after this procedure, she became pregnant and, subsequently, successfully
and safely vaginally delivered a healthy female baby weighing 3250 g at 38+1
weeks' gestation. The delivery did not involve perineal laceration by lateral
episiotomy. To the best of our knowledge, this is the first reported case of
successful vaginal delivery at term after vaginal reconstruction with labium
minus flaps in a patient with vaginal atresia.
PMID- 28422366
TI - Oral paracoccidioidomycosis: Retrospective analysis of 55 Brazilian patients.
AB - Paracoccidioidomycosis (PCM) is a rare fungal infection in the world, but endemic
and acquired exclusively in Latin America, with the highest prevalence in South
America and Brazil, particularly. Changes in oral cavity are common and
constitute the first clinical manifestation in many patients. The aim of this
study was to describe the prevalence of oral PCM and analyse the profile of the
disease and patients. Retrospective research, consisting of information present
in the medical records in the period 1998-2015, whose histopathological diagnosis
was oral PCM. Fifty-five oral PCM cases were confirmed. Of these patients, 90.9%
were males and 9.1% were females. The average age was 49.66 years and the most
reported occupation was rural workers. The painful symptomatology was present in
61.82% of patients. Erythematous lesions were predominant in 73% of them. In
single lesions (22 cases), the most common locations were jugal mucosa and
tongue. In multiple involvement (30 cases), the most affected regions were lips,
jugal mucosa and alveolar ridge. Epidemiology of PCM, was similar to several
other studies, especially in Brazil. This is the most important fungal infection
in Latin America and the recognition of oral lesions is extremely important, as
is often the first and in many cases the only manifestation of the disease.
PMID- 28422367
TI - Microtensile Bond Strength of a Resin Cement to Silica-Based and Y-TZP Ceramics
Using Different Surface Treatments.
AB - PURPOSE: To evaluate the effects of different surface treatments on the
microtensile bond strength (MUTBS) of bonding between resin cement and lithia or
zirconia-based ceramics using an in vitro study. MATERIALS AND METHODS: Three
zirconia ceramic blocks (IPS e.max ZirCAD) and three lithium disilicate ceramic
blocks (IPS e.max CAD) were sintered and duplicated in resin composite. The
zirconia specimens underwent various treatments (n = 1): (i) Sandblast + primer
(ZiSa); (ii) sandblast + laser irradiation + primer (ZiSaLa); or (iii) laser
irradiation + primer (ZiLa). The lithium disilicate specimens also underwent
various treatments: (i) sandblast + HF + silane (LiSaE); (ii) sandblast + silane
(LiSa); or (iii) sandblast + laser irradiation + silane (LiSaLa). The ceramic
composite blocks were cemented with resin cement and cut to produce bars with
approx. 1 mm2 bonding areas. The specimens were thermocycled, and bond strength
tests were performed in a universal testing machine. The fracture type was
determined by observing the fractured surface under a stereomicroscope. The mean
bond strengths of the specimens were statistically analyzed using one-way ANOVA
and Duncan's tests (alpha = 0.05). RESULTS: Mean comparison of the MUTBS showed
no significant difference between LiSaE and LiSa (p > 0.05), but significant
differences between LiSaE and other groups (p <= 0.01). No significant
differences were found between the ZiSaLa and ZiSa groups (p > 0.05). The modes
of failure in all groups were mostly adhesive (57% to 80%). The mean bond
strengths in laser-irradiated ceramics were significantly lower than those from
other surface treatments. All ZiLa specimens debonded before testing (pretest
failure). CONCLUSIONS: Lithium disilicate ceramic surface treated with a
combination of sandblasting and silane application provided a bond strength
comparable to that provided by sandblasting in combination with acid etching and
applying silane. Groups treated with laser irradiation had significantly lower
bond strengths than other groups.
PMID- 28422368
TI - Safety and efficacy of pulmonary vein isolation using a surround flow catheter
with contact force measurement capabilities: A multicenter registry.
AB - INTRODUCTION: Pulmonary vein (PV) isolation is the cornerstone of catheter
ablation in patients with atrial fibrillation (AF). Surround flow and contact
force (CF) measurement capabilities might enhance procedure efficacy and safety.
We report on the safety and midterm efficacy of a novel ablation catheter for PV
isolation in patients with AF. METHODS AND RESULTS: Two hundred thirty-three
consecutive patients (57 +/- 11 years, 76% males, 51% with structural heart
disease), referred for paroxysmal (157) or persistent (76) AF, underwent PV
isolation by a surround flow catheter with CF measurement capability in four
centers. Ablation was guided by electroanatomic mapping allowing radiofrequency
(RF) energy delivery in the antral region aiming at PV isolation. Mean overall
procedure time was 100 +/- 42 minutes with a mean fluoroscopy time of 6 +/- 5
minutes. Mean ablation time was 31+/-15 minutes; 99% of the targeted veins were
isolated. The mean CF value during ablation was 13 +/- 4 g. Intraprocedural early
(30 minutes) PV reconnection occurred in 12% PVs, and all PVs were effectively
reisolated. One pericardial effusion and five groin hematomas were reported.
During a mean follow-up of 12 +/- 6 months, 30 (12.9%) (10% paroxysmal AF vs. 18%
persistent AF, P = 0.07) patients had an atrial arrhythmias recurrence.
CONCLUSIONS: In this multicenter registry, RF ablation using a new surround flow
catheter, with CF sensor, resulted as feasible, achieving a high rate of isolated
PVs. Procedural and fluoroscopy times and success rates were comparable with
other techniques with a low complication rate.
PMID- 28422369
TI - What impact do questionnaire length and monetary incentives have on mailed health
psychology survey response?
AB - OBJECTIVES: Response rates to health-related surveys are declining. This study
tested two strategies to improve the response rate to a health psychology survey
mailed through English general practices: (1) sending a shortened questionnaire
and (2) offering a monetary incentive to return a completed questionnaire.
DESIGN: Randomized controlled trial. METHODS: Adults (n = 4,241) aged 45-59
years, from four General Practices in South-East England, were mailed a survey on
attitudes towards bowel cancer screening. Using a 2 * 4 factorial design,
participants were randomized to receive a 'short' (four A4 pages) or a 'long'
(seven A4 pages) questionnaire, and one of four monetary incentives to return a
completed questionnaire - (1) no monetary incentive, (2) L2.50 shop voucher, (3)
L5.00 shop voucher, and (4) inclusion in a L250 shop voucher prize draw. Age,
gender, and area-level deprivation were obtained from the General Practices.
RESULTS: The overall response rate was 41% (n = 1,589). Response to the 'short'
questionnaire (42%) was not significantly different from the 'long' questionnaire
(40%). The L2.50 incentive (43%) significantly improved response rates in
univariate analyses, and remained significant after controlling for age, gender,
area-level deprivation, and questionnaire length. The L5.00 (42%) and L250 prize
draw (41%) incentives had no significant impact on response rates compared to no
incentive (38%). CONCLUSIONS: A small monetary incentive (L2.50) may slightly
increase response to a mailed health psychology survey. The length of the
questionnaire (four pages vs. seven pages) did not influence response. Although
frequently used, entry into a prize draw did not increase response. Achieving
representative samples remains a challenge for health psychology. Statement of
contribution What is already known on this subject Response rates to mailed
questionnaires continue to decline, threatening the representativeness of data.
Prize draw incentives are frequently used but there is little evidence to support
their efficacy. Research on interactions between incentives, questionnaire
length, and demographics is lacking. What does this study add Contrary to
previous findings, questionnaire length did not influence response rate. A L2.50
incentive increased response, while incentives of L5.00 and a L250 prize draw did
not. Achieving representative samples to questionnaires remains a challenge for
health psychology.
PMID- 28422370
TI - Leisure riding horses: research topics versus the needs of stakeholders.
AB - Horses intended for leisure riding do not undergo any selection and most often
retired sports horses or defective horses are chosen, as a low selling price
determines their purchase by a leisure riding center. Unfortunately, horses
bought at low prices usually have low utility value, are difficult to handle,
require a special or individual approach and do not provide satisfaction in
riding. However, neither modern horse breeding nor scientific research address
the need to breed horses for leisure activities. There is no clear definition of
a model leisure horse and criteria or information for its selection are not
readily available in scientific publications. A wide spectrum of research methods
may be used to evaluate various performance traits in horses intended for leisure
activities. The fact that the population of recreational horses and their riders
outnumber sporting horses should attract the special attention of scientific
research. Their utility traits need to be determined with modern technology and
methods in the same way they are for sporting horses. Such a system of evaluation
would be very helpful for riders.
PMID- 28422372
TI - Effect of urine creatinine level during pregnancy on dipstick test.
AB - AIM: Dipstick results for proteinuria are affected by urine concentration, and
thus urine creatinine concentration ([Cr]). This study was performed to determine
whether spot urine [Cr] changes significantly during pregnancy, leading to a
significantly different false-negative rate (FNR) on dipstick test between
trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in
631 spot urine samples with negative/equivocal dipstick from 425 pregnant women.
False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg.
RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3
477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n
= 344), and third (n = 191) trimester urine samples, respectively (P = 0.000,
Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing
gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than
that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third
trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was
47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute
urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining
611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046).
CONCLUSIONS: Urine samples in the second and third trimesters were more likely to
be diluted compared with the first trimester. This was associated with high FNR
in third trimester urine samples.
PMID- 28422371
TI - Effects of M1 and M4 activation on excitatory synaptic transmission in CA1.
AB - Hippocampal networks are particularly susceptible to dysfunction in many
neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's
disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the
hippocampus, receives glutamatergic input from both hippocampal CA3 and
entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA)
pathways, respectively. SC and TA inputs to CA1 are thought to be differentially
involved in the retrieval of previously stored memories versus the encoding of
novel information, and switching between these two crucial hippocampal functions
is thought to critically depend on acetylcholine (ACh) acting at muscarinic
receptors. In this study, we aimed to determine the roles of specific subtypes of
muscarinic receptors in mediating the neuromodulatory effects of ACh on
glutamatergic synaptic transmission in the SC and TA pathways of CA1. Using
selective pharmacological activation of M1 or M4 receptors along with
extracellular and intracellular electrophysiology recordings from adult rat
hippocampal slices, we demonstrate that activation of M1 receptors increases
spontaneous spike rates of neuronal ensembles in CA1 and increases the intrinsic
excitability of pyramidal neurons and interneurons. Selective activation of M4
receptors inhibits glutamate release in the SC pathway, while leaving synaptic
transmission in the TA pathway comparatively intact. These results suggest
specific mechanisms by which M1 and M4 activation may normalize CA1 circuit
activity following disruptions of signaling that accompany neurodegenerative
dementias or neuropsychiatric disorders. These findings are of particular
interest in light of clinical findings that xanomeline, an M1/M4 preferring
agonist, was able to improve cognitive and behavioral symptoms in patients with
Alzheimer's disease or schizophrenia.
PMID- 28422373
TI - Longitudinal recovery of local neuronal activity and consciousness level in
acquired brain injury.
AB - Decreased brain activity in the default mode network, particularly in the
precuneus (PCU), has been consistently shown in acquired brain injury (ABI)
patients. However, it is unclear whether resting-state brain activity recovers
longitudinally in ABI patients and whether functional activity restoration is
associated with improvements in consciousness level. Here, resting-state fMRI
data were acquired from 23 ABI patients and 30 age- and gender-matched controls
with two longitudinal observations for each participant. The fMRI data were
analyzed using amplitude of low-frequency fluctuation (ALFF) to measure the
fluctuation strength of local spontaneous activity, and seed-based functional
connectivity was used to measure functional relationship with the seed region in
the whole brain. The level of consciousness was assessed using the Glasgow Coma
Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) on both scanning days of the
patients. Interaction effect between the two groups and two scans in ALFF was
observed in the PCU, which was driven by restored ALFF in the ABI, while a stable
ALFF in the control group. Moreover, restoration of ALFF in the PCU correlated
with improvements in both the CRS-R and GCS. Specifically, recovery of ALFF in
the PCU primarily reflected the signals of the slow-4 frequency band (0.027-0.073
Hz). Based on the functional connectivity maps of the PCU, we observed a
nonsignificant interaction effect or correlation with consciousness level. These
findings suggest local activity in the PCU but possibly not its functional
connectivity, is related to the longitudinal changes in behavioral responsiveness
in ABI. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422374
TI - Significant curative functions of the mesenchymal stem cells on methotrexate
induced kidney and liver injuries in rats.
AB - Mesenchymal stem cells (MSCs) curative effects on methotrexate (MTX)-induced
kidney and liver injuries remain elusive. Therefore, rats were divided into five
groups, rats received MTX orally (14 mg/kg) as a single dose/week for 2 weeks,
groups 3 and 4 were injected once with 2 * 106 cells bone marrow MSCs and adipose
derived MSCs, respectively. The last group administered dexamethasone (DEX) (0.5
mg/kg, p.o) for 7 days. MTX caused marked increase in malondialdehyde and
nitrite/nitrate concentrations. However, MTX administration decreased reduced
glutathione content plus catalase activity. In addition, MTX caused a significant
increment in kidney and liver biomarkers levels. Moreover, MTX showed renal
tubules vacuolation and necrosis of hepatocytes, as well expression of caspase-3
and nuclear factor kappa beta in kidney and liver tissues were observed. MSCs
treatment alleviated previous side effects induced by MTX. MSCs improved
nephrotoxicity and hepatotoxicity induced by MTX to a better extent as compared
with DEX.
PMID- 28422375
TI - Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology
treated with pegylated liposomal doxorubicin and bevacizumab.
AB - Hepatoid carcinomas are undifferentiated epithelial carcinomas that are
pathologically similar to hepatocellular carcinoma, but occur in a variety of
organs. Hepatoid carcinomas, as strictly defined, typically produce alpha
fetoprotein. In addition, a standard effective chemotherapy regimen for hepatoid
carcinoma has yet to be established. We present a case of advanced primary
ovarian cancer that was pathologically similar to hepatoid carcinoma without
staining for alpha-fetoprotein or hepatocyte paraffin 1. The primary ovarian,
metastatic, and recurrent tumors shared similar pathological characteristics.
Fourth-line chemotherapy with pegylated liposomal doxorubicin and bevacizumab was
effective in treating the recurrent tumor, even though this disease had recurred
three times.
PMID- 28422376
TI - Spontaneous remission of hepatitis B virus reactivation during direct-acting
antiviral agent-based therapy for chronic hepatitis C.
AB - The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C
virus (HCV) infection has been reported to cause hepatitis B virus (HBV)
reactivation. However, the actual conditions of HBV reactivation and the ideal
timing of medical intervention have not been fully evaluated. We report the cases
of two female patients dually infected with HBV and HCV. Both patients were
inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after
the initiation of DAA-based therapy, the serum HBV DNA levels gradually increased
during DAA-based therapy, with the peak serum HBV DNA levels observed at 16 weeks
after the initiation of DAA-based therapy in both cases. Subsequently, we checked
the serum HBV DNA levels closely every week several times. Fortunately, the serum
HBV DNA levels gradually decreased without medical intervention. Neither case
developed an alanine aminotransferase flare-up. The HCV genotypes were 2a and 1b,
and the DAA-based therapies of Cases 1 and 2 were 12 weeks of
sofosbuvir/ribavirin and ombitasvir/paritaprevir/ritonavir, respectively. The
significance of our case reports is the demonstration of the existence of
spontaneous remission of HBV reactivation that developed during DAA-based
therapy, the avoidance of intervention of nucleot(s)ide analogs by frequent
monitoring of serum HBV DNA levels, and development of HBV reactivation
regardless of the viral genotype or class of DAA. In conclusion, the close
monitoring of serum HBV DNA levels during and after DAA-based therapy is
essential and medical intervention for HBV reactivation should be carefully
considered on an individual basis.
PMID- 28422377
TI - Intraperitoneal gardiquimod protects against hepatotoxicity through inhibition of
oxidative stress and inflammation in mice with sepsis.
AB - Many reports recapitulate the contribution of reactive oxygen species (ROS) over
accumulation to the organ damage; it is of significance to strictly target ROS
production. In this study, we evaluated the potential role of TLR7 agonist
gardiquimod (GDQ) in oxidative stress (OS) in liver injury induced by sepsis.
Here, we observed that intraperitoneal pretreatment with GDQ dramatically
elevated the septic survival rate and effectively attenuated the septic liver
injury. Interestingly, the increased ROS and inflammatory factor IL-6 levels were
reversed after GDQ intervention. Subsequently, Western blot was employed to
determine the definite mechanism. As expected, it was showed that the
upregulation of c-Jun N-terminal kinase (JNK)/c-Jun pathway in liver of septic
animals was considerably suppressed by GDQ pre-exposure. Our current result
highlight that pre-administration of GDQ ameliorated sepsis induced
hepatotoxicity and reduced the generation of IL-6 and OS responses, which was
associated with downregulation of JNK/c-Jun pathway. Our strategies might be
ultimately beneficial in mitigating liver injury symptom.
PMID- 28422378
TI - Cellular retinoic acid bioavailability in various pathologies and its therapeutic
implication.
AB - Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling
molecule in various cell types. We found that RA depletion caused by expression
of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating
CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that
the biological effect of RA on target cells is primarily determined by "cellular
RA bioavailability", which is defined as the RA level in an individual cell,
rather than by the serum concentration of RA. Consistently, stellate cells store
approximately 80% of vitamin A in the body, and the state of cellular RA
bioavailability regulates their function. Based on the similarities between
stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate
tight junction-based endothelial integrity in a paracrine manner. Since diabetic
retinopathy is characterized by increased vascular permeability in its early
pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes,
resulting in suppression of vascular leakiness. RA also attenuated the loss of
the epithelial barrier in murine experimental colitis. The concept of "cellular
RA bioavailability" in various diseases will be directed at understanding various
pathologies caused by RA insufficiency, implying the potential feasibility of a
therapeutic strategy targeting the stellate cell system.
PMID- 28422379
TI - Increased 5-hydroxymethylation levels in the hippocampus of rat extinguished from
cocaine self-administration.
AB - Drug craving and relapse risk during abstinence from cocaine are thought to be
caused by persistent changes in transcription and chromatin regulation. Although
several brain regions are involved in these processes, the hippocampus seems to
play an important role in context-evoked craving and drug-seeking behavior. Only
a few studies have examined epigenetic alterations during a period of cocaine
abstinence. To investigate the effects of cocaine abstinence on DNA methylation
and gene expression, rats that self-administered the drug underwent cocaine
abstinence in two time points with extinction training. During the cocaine
extinction, we observed elevated global 5-hydroxymethylcytosine(5-hmC) levels
with a concurrent increase in Tet3 transcript levels. Moreover, we did not find
significant alterations in the levels of Tet3 mRNA and 5-hmC in rats subjected to
cocaine abstinence without extinction training. Additionally, our findings
demonstrated that the expression of Tet3 target genes was activated. Besides,
altered DNA methylation was detected at promoter regions of miRNAs, such as miR
30d and miR-let7i. Further in silico analysis provided evidence that these two
molecules targeted the 3' UTR region of the Tet3 gene and thus may contribute to
its post-transcriptional regulation. This study has presented novel findings in
the hippocampus of rats that underwent extinction training following cocaine self
administration. The alterations in the Tet3 gene expression and the level of 5
hmC may play an important role in extinction learning and the reduction of
subsequent cocaine seeking.
PMID- 28422380
TI - Comparing the long-acting and short-acting forms of gonadotropin-releasing
hormone agonists in the long protocol of IVF/ICSI Cycles: A retrospective study.
AB - AIM: This study aimed to compare the efficacy of long- and short-acting
gonadotropin-releasing hormone agonist on clinical outcomes of in vitro
fertilization/intracytoplasmic sperm injection (IVF/ICSI) long protocol cycles.
METHODS: In this retrospective study, 478 patients were enrolled from October
2012 to November 2014. The pituitary downregulation result, serum hormone levels,
gonadotropin (Gn) dose during controlled ovarian hyperstimulation, and outcome of
IVF/ICSI-embryo transfer were compared between the two groups. RESULTS: Compared
with the long-acting group, in the short-acting group the duration of
downregulation and stimulation was significantly shorter; the total Gn doses,
cost of an IVF cycle, rate of ovarian hyperstimulation syndrome, superior-quality
embryo rate, and implantation rate were significantly lower; and the serum
luteinizing hormone concentrations on the day of Gn and human chorionic
gonadotropin administration were significantly higher. The serum estradiol level
on the day of human chorionic gonadotropin was higher in the long-acting group.
However, no significant differences were noted in other parameters. CONCLUSION:
The long-acting group was associated with greater amounts of Gn and a longer
duration of use for ovarian stimulation. This increased the cost per IVF cycle
and may have had a detrimental effect on the pregnancy outcome because of a
subsequent increase in the rate of ovarian hyperstimulation syndrome and decrease
in the superior-quality embryo rate and implantation rate.
PMID- 28422381
TI - Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam
commissioning data.
AB - PURPOSE: Commissioning beam data for proton spot scanning beams are compared for
the first two Varian ProBeam sites in the United States, at the Maryland Proton
Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition,
the extent to which beams can be matched between gantry rooms at MPTC is
investigated. METHOD: Beam data for the two sites were acquired with independent
dosimetry systems and compared. Integrated depth dose curves (IDDs) were acquired
with Bragg peak ion chambers in a 3D water tank for pencil beams at both sites.
Spot profiles were acquired at different distances from the isocenter at a gantry
angle of 0 degrees as well as a function of gantry angles. Absolute dose
calibration was compared between SPTC and the gantries at MPTC. Dosimetric
verification of test plans, output as a function of gantry angle, monitor unit
(MU) linearity, end effects, dose rate dependence, and plan reproducibility were
compared for different gantries at MPTC. RESULTS: The IDDs for the two sites were
similar, except in the plateau region, where the SPTC data were on average 4.5%
higher for lower energies. This increase in the plateau region decreased as
energy increased, with no marked difference for energies higher than 180 MeV.
Range in water coincided for all energies within 0.5 mm. The sigmas of the spot
profiles in air were within 10% agreement at isocenter. This difference increased
as detector distance from the isocenter increased. Absolute doses for the
gantries measured at both sites were within 1% agreement. Test plans, output as
function of gantry angle, MU linearity, end effects, dose rate dependence, and
plan reproducibility were all within tolerances given by TG142. CONCLUSION: Beam
data for the two sites and between different gantry rooms were well matched.
PMID- 28422382
TI - Quantum dots-based fluorescence resonance energy transfer biosensor for
monitoring cell apoptosis.
AB - The development of advanced methods for accurately monitoring cell apoptosis has
extensive significance in the diagnostic and pharmaceutical fields. In this
study, we developed a rapid, sensitive and selective approach for the detection
of cell apoptosis by combining the site-specific recognition and cleavage of the
DEVD-peptide with quantum dots (QDs)-based fluorescence resonance energy transfer
(FRET). Firstly, biotin-peptide was conjugated on the surface of AuNPs to form
AuNPs-pep through the formation of an Au-S bond. Then, AuNPs-pep-QDs nanoprobe
was obtained through the connection between AuNPs-pep and QDs. FRET is on and the
fluorescence of QDs is quenched at this point. The evidence of UV-vis spectra,
transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR)
spectroscopy revealed that the connection was successful. Upon the addition of
apoptosis cell lysis solution, peptide was cleaved by caspase-3, and AuNPs was
dissociated from the QDs. At this time, FRET is off, and thus the QDs
fluorescence was recovered. The experimental conditions were optimized in terms
of ratio of peptide to AuNPs, buffer solution, and the temperature of conjugation
and enzyme reaction. The biosensor was successfully applied to distinguishing
apoptosis cells and normal cells within 2 h. This study demonstrated that the
biosensor could be utilized to evaluate anticancer drugs.
PMID- 28422383
TI - Liquid and subcritical fluid chromatographic enantioseparation of Nalpha -Fmoc
proteinogenic amino acids on Quinidine-based zwitterionic and anion-exchanger
type chiral stationary phases. A comparative study.
AB - Stereoselective high-performance liquid chromatographic and subcritical fluid
chromatographic separations of 19 Nalpha -Fmoc proteinogenic amino acid
enantiomers were carried out by using Quinidine-based zwitterionic and anion
exchanger-type chiral stationary phases Chiralpak ZWIX(-) and QD-AX. For
optimization of retention and enantioselectivity, the ratio of bulk solvent
components (MeOH/MeCN, H2 O/MeOH, or CO2 /MeOH) and the nature and concentration
of the acid and base additives (counter- and co-ions) were systematically varied.
The effect of column temperature on the enantioseparation was investigated and
thermodynamic parameters were calculated from the van't Hoff plots ln alpha vs.
1/T. The thermodynamic parameters revealed that the enantioseparations were
enthalpy-driven. The elution sequence was determined in all cases and with the
exception of Fmoc-Cys(Trt)-OH, it was identical on both chiral stationary phases
whereby the L-enantiomers eluted before the D-enantiomers.
PMID- 28422384
TI - Natural antioxidant flavonoids in formalin-induced mice paw inflammation;
inhibition of mitochondrial sorbitol dehydrogenase activity.
AB - Flavonoids have reported to cover interesting multiple pharmacological
properties. This study evaluated the effect of apigenin or silymarin in paw
inflammation induced by formalin in mice. Mice were divided into four groups: I:
positive control group; II: apigenin, 3 mg/kg (i.p.); III: silymarin 50 mg/kg
(p.o.); IV: meloxicam 10 mg/kg (p.o.), the reference drug. Therapies were
administered once a day for 7 days. The curative effects were assessed on
inflammatory, oxidative stress and neurotransmitter biomarkers, and apoptosis.
Both flavonoids induced marked improvement in paw licking time, paw edema %,
malondialdehyde content, superoxide dismutase, and sorbitol dehydrogenase
activities, with slight progress in paw interlukin-1beta. Additionally, silymarin
augmented brain content of dopamine and norepinephrine. Furthermore, flavonoids
induced marked decline in extent of apoptosis. So, the results spotlight on the
good influence of apigenin or silymarin as anti-inflammatory, antioxidant, and
antiapoptotic agents in formalin-induced mice paw inflammation to even a better
extent than meloxicam.
PMID- 28422385
TI - Genital bleeding hemostasis in gynecologic neoplasm with balloon tamponade: New
treatment option.
AB - Genital bleeding is the most common and serious complication in gynecologic
malignancy. Different techniques are available for the control of severe
bleeding, but standard treatment strategies have not been determined. Herein we
report on the successful use of the balloon technique in two cases of genital
bleeding in uterine neoplasm. The first case was of advanced cervical cancer with
massive genital bleeding during radiotherapy. A metreurynter (mini-metro) was
inserted into the vagina and hemostasis was indirectly achieved in the vaginal
hematoma. The other case was of postoperative recurrent bleeding after cervical
conization. A Foley balloon catheter was inserted into the endocervical canal and
balloon tamponade directly stopped the bleeding. This technique is safe for
massive genital bleeding in some cases of gynecological cancer, and can be
conventionally performed regardless of the facility or department. The need for
invasive treatment for fatal bleeding in gynecological cancer in which gauze
packing is ineffective may be avoided by balloon tamponade without serious
complications.
PMID- 28422386
TI - Corticosteroid might reduce serum levels of pro-inflammatory cytokines in
fulminant hepatitis: A case series.
AB - AIM: There are no beneficial therapies except for emergency liver transplantation
for acute liver failure (ALF). However, in Japan, which has a serious problem in
the shortage of donor livers, therapies other than transplantation must be
further investigated for patients with ALF. Pro-inflammatory cytokines promoting
tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS)
influences monocyte/macrophage differentiation, by suppressing pro-inflammatory
genes, indicating CS treatment might be beneficial during the early phase of ALF.
Our aim was to elucidate the efficacy of CS pulse therapy in decreasing pro
inflammatory cytokine levels in the early stage of ALF. METHODS: Ten consecutive
adult Japanese patients with fulminant hepatitis in the early stage, three
treated with artificial liver support (ALS) and CS pulse therapy (ALS + CS group)
and seven treated with ALS (ALS group), were enrolled. Clinical and biochemical
data on admission were matched between the groups and retrospectively analyzed
for serum concentrations of interleukin-6, tumor necrosis factor-alpha, and
interleukin-1beta over a 2-week period. RESULTS: Mean cytokine levels on
admission were not different between the two groups. Tumor necrosis factor-alpha
was significantly reduced on day 7 in patients with CS. Serum levels of pro
inflammatory cytokines tended to be reduced in patients with CS compared to those
without during the observation period, although the differences were not
significant. CONCLUSIONS: It might be possible that introduction of CS pulse
therapy in the early stage of ALF could reduce levels of pro-inflammatory
cytokines, which might inhibit the cascade of progression of ALF.
PMID- 28422387
TI - Should we be putting our scalpels down? Is HIFU the answer to fertility-sparing
fibroid treatment?
PMID- 28422388
TI - Comparison of the effectiveness of two different interventions to reduce
preoperative anxiety: A randomized controlled study.
AB - This study was conducted to determine and compare the effectiveness of nature
sounds and relaxation exercises for reducing preoperative anxiety. A repeated
measures randomized controlled trial design was used. We divided 159 preoperative
patients into three groups: nature sounds (n = 53), relaxation exercises (n =
53), and control groups (n = 53). We evaluated anxiety using the visual analog
scale and state anxiety inventory scores immediately before, immediately after,
and 30 min after interventions in nature sounds and relaxation exercises groups,
and silent rest in the control. We found no differences between the measurement
values in the intervention groups, but we did observe a difference between the
intervention and control groups. The two interventions were similarly effective
in reducing preoperative anxiety. These simple and low-cost interventions can be
used to reduce preoperative anxiety in surgical clinics.
PMID- 28422389
TI - Triosephosphate isomerase tyrosine nitration induced by heme-NaNO2 -H2 O2 or
peroxynitrite: Effects of different natural phenolic compounds.
AB - Peroxynitrite and heme peroxidases (or heme)-H2 O2 -NaNO2 system are the two
common ways to cause protein tyrosine nitration in vitro, but the effects of
antioxidants on reducing these two pathways-induced protein nitration and
oxidation are controversial. Both nitrating systems can dose-dependently induce
triosephosphate isomerase (TIM) nitration, however, heme-H2 O2 -NaNO2 was less
destructive to protein secondary structures and led to more nitrated tyrosine
residue than 3-morpholinosydnonimine hydrochloride (SIN-1, a peroxynitrite
donor). Both of desferrioxamine and catechin could inhibit TIM nitration induced
by heme-H2 O2 -NaNO2 and SIN-1 and protein oxidation induced by SIN-1, but
promoted heme-H2 O2 -NaNO2 -induced protein oxidation. Moreover, the antagonism
of natural phenolic compounds on SIN-1-induced tyrosine nitration was consistent
with their radical scavenging ability, but no similar consensus was found in heme
H2 O2 -NaNO2 -induced nitration. Our results indicated that peroxynitrite and
heme-H2 O2 -NaNO2 -induced protein nitration was different, and the later one
could be a better model for anti-nitration compounds screening.
PMID- 28422390
TI - Naringin abates adverse effects of cadmium-mediated hepatotoxicity: An
experimental study using HepG2 cells.
AB - This study investigated the protective potential of Naringin (NIN) against
cadmium chloride (CdCl2 ) mediated hepatotoxicity using human hepatocellular
carcinoma (HepG2) cells. An optimal concentration of NIN (5 MUM) was potent
enough to confer cytoprotection against CdCl2 (50 MUM) as was observed by MTT
assay. Preconditioning with NIN maintained redox homeostasis, mitochondrial
membrane potential, and reduced apoptosis as marked by decrease in the percentage
sub-G0 /G1 and Annexin V-FITC/propidium iodide positive cells (apoptotic). NIN
pretreatment maintained the levels of protein thiol along with endogenous
activities of Superoxide dismutase, Glutathione S-transferase, and Catalase and
lowered lipid peroxidation. Decreased Bax/Bcl2 ratio along with reduced Caspase 3
cleavage and Cytochrome c release indicated that NIN conditioning blocked
mitochondrial-mediated apoptosis. Increased Nrf2 and metallothionein (MT) acted
as adaptive response in the presence of cadmium. Thus, the protective mechanism
of NIN is attributed to its antioxidant potential which aids in redox homeostasis
and prevents CdCl2 mediated cytotoxicity.
PMID- 28422391
TI - MR elastography detection of early viscoelastic response of the murine
hippocampus to amyloid beta accumulation and neuronal cell loss due to
Alzheimer's disease.
AB - PURPOSE: To investigate in vivo viscoelastic parameters related to early
histopathological changes in the hippocampus and the cortex in early, preclinical
Alzheimer's disease (AD) stages. MATERIALS AND METHODS: Magnetic resonance
elastography (MRE) was applied to female APP23 mice, an established transgenic
mouse model of AD, at three different stages early in disease progression. To
investigate the potential therapeutic effects of physical, cognitive, and social
stimulation on brain viscoelasticity and histopathological characteristics, MRE
was also applied after exposing young APP23 mice to environmentally enriched cage
conditions (ENR), for 1, 12, or 24 weeks, which corresponds to adolescent, young
adult, and adult age at the time of analysis. RESULTS: Viscosity in the
hippocampus of APP23 mice is lower than in controls (CTR) (P = 0.005) and does
not increase with age, as in CTR mice (adolescent vs. young-adult: P = 1.000, vs.
adult: P = 0.493, young-adult vs. adult: P = 1.000). Hippocampal cell numbers
decrease with disease progression in APP23 mice (P < 0.001). Elasticity in the
hippocampus is also reduced in APP23 mice (P = 0.024) but increases (P = 0.027)
with disease progression. ENR in APP23 mice transiently increased hippocampal
cell numbers (P = 0.002) but not viscosity (P = 0.838). CONCLUSION: MRE detects
alterations in viscoelasticity in the hippocampus related to early
histopathological changes in the APP23 mouse model of AD. LEVEL OF EVIDENCE: 1
Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:105-114.
PMID- 28422392
TI - Hepatic artery reconstruction in living donor liver transplantation using
surgical loupes: Achieving low rate of hepatic arterial thrombosis in 741
consecutive recipients-tips and tricks to overcome the poor hepatic arterial
flow.
AB - The reconstruction of the hepatic artery (HA) is the most complex step in living
donor liver transplantation (LDLT) because of the smaller diameter of the artery
and the increased risk of HA-related complications. Because of the smaller
diameter of the HA, many centers use a microsurgical technique with interrupted
sutures for arterial anastomosis. The aim of our study was to retrospectively
investigate the outcomes after HA reconstruction performed under magnifying
loupes using the "parachute technique." From August 1, 2002 to August 31, 2016,
LDLT was performed in 766 recipients. HA reconstruction for the initial 25 LDLT
surgeries was performed using a microsurgery technique (era 1). From May 2007
until the end date, HA reconstruction was performed in 741 recipients by a
"parachute technique" under surgical loupes (era 2). HA reconstruction was
performed using surgical loupes in 737 adults (male:female, 526:211) and 4
pediatric patients (male:female, 3:1). The average diameter of the donor graft HA
was 2.8 mm (range, 1-6.5 mm). The most notable factor in this era was the quick
HA anastomosis procedure with a mean time of 10 +/- 5 minutes (range, 5-30
minutes). In era 2, 9 (1.21%) patients developed hepatic artery thrombosis (HAT),
whereas 2 patients developed nonthrombotic HA-related complications. Extra
anatomic HA reconstruction was performed in 14 patients due to either primary HA
anastomosis failure or a poor caliber recipient HA. The use of magnifying
surgical loupes to perform HA reconstruction is safe, feasible, and yields a low
incidence of HA-related complications. The "parachute technique" for HA
reconstruction can achieve a speedy reconstruction without increasing the risk of
HAT. Liver Transplantation 23 887-898 2017 AASLD.
PMID- 28422393
TI - Accuracy and response time of dual biomarker model of insulin-like growth factor
binding protein-1/ alpha fetoprotein (Amnioquick duo+) in comparison to placental
alpha-microglobulin-1 test in diagnosis of premature rupture of membranes.
AB - AIM: The aim of this study was to determine accuracy and response time of duo of
insulin-like growth factor binding protein-1 (IGFBP-1)/alpha-fetoprotein
(Amnioquick duo+) versus placental alpha-microglobulin-1 (PAMG-1) in diagnosing
premature rupture of membranes (PROM). METHODS: A multicenter prospective study
was conducted among women with features suggestive of PROM between 24 and 42
gestational weeks (GW). PROM was confirmed post-delivery based on presence of any
two of these criteria: delivery within 48 h to 7 days, chorioamnionitis,
membranes overtly ruptured at delivery, and adverse perinatal outcomes strongly
correlated with prolonged PROM. Response time analysis was also done. Outcome
measures included specificity, sensitivity, positive predictive value, negative
predictive value, accuracy, and response time for both tests. RESULTS:
Sensitivity, specificity, and accuracy for Amnioquick duo+ were 97.9%, 97.6%, and
97.9%, which were higher than the levels for PAMG-1, of 95.3%, 90.0%, and 95.7%,
respectively (not significant). Accuracy of Amnioquick duo+ versus PAMG-1 in
equivocal (pooling = negative) cases was (98.4% vs 96.8%) at >=34 GW but each was
100.0% at <34 GW (not significant). Overall diagnostic concordance rate of
Amnioquick duo+ and PAMG-1 was 97.0% and both have equal positive predictive
value (99.5%). Response time analysis showed that the overall response time of
PAMG-1 was 4.5% higher than that of Amnioquick duo+. CONCLUSION: This is the
largest study to date to reveal that Amnioquick duo+ and PAMG-1 have a
comparatively high diagnostic accuracy in identifying women with PROM, with a
concordance rate of 97.0%. The diagnostic response time of Amnioquick duo+
appears shorter. In equivocal cases, accuracy of Amnioquick duo+ was equal to
that of the PAMG-1.
PMID- 28422394
TI - Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic
involvement: Extending the phenotypic spectrum.
AB - We previously reported exome sequencing in a short-rib thoracic dystrophy (SRTD)
cohort, in whom recessive mutations were identified in SRTD-associated genes in
10 of 11 cases. A heterozygous stop mutation in the known SRTD gene WDR60 was
identified in the remaining case; no novel candidate gene/s were suggested by
homozygous/compound heterozygous analysis. This case was thus considered
unsolved. Re-analysis following an analysis pipeline update identified a
homozygous mutation in C21orf2 (c.218G > C; p.Arg73Pro). This homozygous variant
was previously removed at the quality control stage by the default GATK parameter
"in-breeding co-efficient." C21orf2 was recently associated with both Jeune
asphyxiating thoracic dystrophy (JATD) and axial spondylometaphyseal dysplasia
(axial SMD); this particular mutation was reported in homozygous and compound
heterozygous state in both conditions. Our case has phenotypic features of both
JATD and axial SMD; and the extent of thoracic involvement appears more severe
than in other C21orf2-positive cases. Identification of a homozygous C21orf2
mutation in this case emphasizes the value of exome sequencing for simultaneously
screening known genes and identifying novel genes. Additionally, it highlights
the importance of re-interrogating data both as novel gene associations are
identified and as analysis pipelines are refined. Finally, the severity of
thoracic restriction in this case adds to the phenotypic spectrum attributable to
C21orf2 mutations.
PMID- 28422395
TI - Chiral determination of cinchonine using an electrochemiluminescent sensor with
molecularly imprinted membrane on the surfaces of magnetic particles.
AB - A novel molecular imprinting electrochemiluminescence sensor for detecting chiral
cinchonine molecules was developed with a molecularly imprinted polymer membrane
on the surfaces of magnetic microspheres. Fe3 O4 @Au nanoparticles modified with
6-mercapto-beta-cyclodextrin were used as a carrier, cinchonine as a template
molecule, methacrylic acid as a functional monomer and N,N'
methylenebisacrylamide as a cross-linking agent. Cinchonine was specifically
recognized by the 6-mercapto-beta-cyclodextrin functional molecularly imprinted
polymer and detected based on enhancement of the electrochemiluminescence
intensity caused by the reaction of tertiary amino structures of cinchonine
molecules with Ru(bpy)32+ . Cinchonine concentrations of 1 * 10-10 to 4 * 10-7
mol/L showed a good linear relationship with changes of the
electrochemiluminescence intensity, and the detection limit of the sensor was
3.13 * 10-11 mol/L. The sensor has high sensitivity and selectivity, and is easy
to renew. It was designed for detecting serum samples, with recovery rates of
98.2% to 107.6%.
PMID- 28422396
TI - A simplified multivisceral transplantation procedure for patients with combined
end-stage liver disease and type 2 diabetes mellitus.
AB - In liver transplant patients with type 2 diabetes mellitus (DM), the disease
worsens after transplantation because of longterm use of diabetogenic
immunosuppressive drugs, making management of those patients a great challenge.
The objective of our study was to evaluate the safety and efficacy of a
simplified multivisceral transplantation (SMT) procedure for the treatment of
patients with end-stage liver disease and concurrent type 2 DM. Forty-four
patients who had pretransplant type 2 DM were included. A total of 23 patients
received SMT, and 21 patients received orthotopic liver transplantation (OLT).
Patient and graft survivals, complications, diabetic control, and quality of life
(QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year
cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the
SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P =
0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from
DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of
biliary complication was significantly higher in the OLT group than that in the
SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the
SMT group than that in the OLT group. In conclusion, the SMT procedure we
described here is a safe and viable option for patients with end-stage live
disease and concurrent type 2 DM. This SMT procedure offers excellent transplant
outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.
PMID- 28422397
TI - A novel radiation protection device based on tungsten functional paper for
application in interventional radiology.
AB - Tungsten functional paper (TFP), which contains 80% tungsten by weight, has
radiation-shielding properties. We investigated the use of TFP for the protection
of operators during interventional or therapeutic angiography. The air kerma rate
of scattered radiation from a simulated patient was measured, with and without
TFP, using a water-equivalent phantom and fixed C-arm fluoroscopy. Measurements
were taken at the level of the operator's eye, chest, waist, and knee, with a
variable number of TFP sheets used for shielding. A Monte Carlo simulation was
also utilized to analyze the dose rate delivered with and without the TFP
shielding. In cine mode, when the number of TFP sheets was varied through 1, 2,
3, 5, and 10, the respective reduction in the air kerma rate relative to no TFP
shielding was as follows: at eye level, 24.9%, 29.9%, 41.6%, 50.4%, and 56.2%; at
chest level, 25.3%, 33.1%, 34.9%, 46.1%, and 44.3%; at waist level, 45.1%, 57.0%,
64.4%, 70.7%, and 75.2%; and at knee level, 2.1%, 2.2%, 2.1%, 2.1%, and 2.1%. In
fluoroscopy mode, the respective reduction in the air kerma rate relative to no
TFP shielding was as follows: at eye level, 24.8%, 30.3%, 34.8%, 51.1%, and
58.5%; at chest level, 25.8%, 33.4%, 35.5%, 45.2%, and 44.4%; at waist level,
44.6%, 56.8%, 64.7%, 71.7%, and 77.2%; and at knee level, 2.2%, 0.0%, 2.2%, 2.8%,
and 2.5%. The TFP paper exhibited good radiation-shielding properties against the
scattered radiation encountered in clinical settings, and was shown to have
potential application in decreasing the radiation exposure to the operator during
interventional radiology.
PMID- 28422398
TI - Do mHealth interventions prevent excessive gestational weight gain?
PMID- 28422399
TI - Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome (CRPS)
Recurrence after Amputation for CRPS, and Failure of Conventional Spinal Cord
Stimulation.
AB - BACKGROUND: Limb amputation is sometimes being performed in long-standing complex
regional pain syndrome (CRPS), although little evidence is available guiding
management decisions, including how CRPS recurrence should be managed. METHODS:
This report details the management of a young soldier with CRPS recurrence 2
years after midtibial amputation for CRPS. RESULTS: Conventional spinal cord
stimulation did not achieve paraesthetic coverage, or pain relief in the stump,
whereas L4 dorsal root ganglion stimulation achieved both coverage and initially
modest pain relief, and over time, substantial pain relief. CONCLUSIONS: Current
evidence does not support the use of amputation to improve either pain or
function in CRPS. Before a decision is made, in exceptional cases, about referral
for amputation, dorsal root ganglion stimulation should be considered as a
potentially effective treatment, even where conventional spinal cord stimulator
treatment has failed to achieve reliable paraesthetic cover. Furthermore, this
treatment may provide pain relief in those patients with CRPS recurrence in the
stump after amputation.
PMID- 28422401
TI - MLC-based penumbra softener of EDW borders to reduce junction inhomogeneities.
AB - Junctions of fields are known to be susceptible to developing cold or hot spots
in the presence of even small geometrical misalignments. Reduction of these dose
inhomogeneities can be accomplished through decreasing the dose gradients in the
penumbra, but currently it cannot be done for enhanced dynamic wedges (EDW). An
MLC-based penumbra softener was developed in the developer mode of TrueBeam
linacs to reduce dose gradients across the side border of EDWs. The movement of
each leaf was individually synchronized with the movement of the dynamic Y jaw to
soften the penumbra in the same manner along the entire field border, in spite of
the presence of the dose gradient of the EDW. Junction homogeneity upon field
misalignment for side-matched EDWs was examined with the MV imager. The fluence
inhomogeneities were reduced from about 30% per mm of shift of the field borders
for the conventional EDW to about 2% per mm for the softened-penumbra plan. The
junction in a four-field monoisocentric breast plan delivered to the Rando
phantom was assessed with film. The dose inhomogeneities across the junction in
the superior-inferior direction were reduced from about 20% to 25% per mm for the
conventional fields to about 5% per mm. The dose near the softened junction of
the breast plan with no shifts did not deviate from the conventional plan by more
than about 4%. The newly-developed softened-penumbra junction of EDW (and/or
open) fields was shown to reduce sensitivity to misalignments without increasing
complexity of the planning or delivery. This methodology needs to be adopted by
the manufacturers for clinical use.
PMID- 28422402
TI - Gypenoside inhibits interleukin-1beta-induced inflammatory response in human
osteoarthritis chondrocytes.
AB - Gypenoside (GP), the main active ingredient of Gynostemma pentaphyllum, possesses
a variety of pharmacological capacities including anti-inflammation, anti
oxidation, and anti-tumor. However, the effects of GP on IL-1beta-stimulated
human osteoarthritis (OA) chondrocytes are still unknown. Therefore, this study
aimed to investigate the anti-inflammatory effects of GP on IL-1beta-stimulated
human OA chondrocytes and explore the possible mechanism. Our results showed that
GP dose-dependently inhibited IL-1beta-induced NO and PGE2 production in human OA
chondrocytes. In addition, treatment of GP inhibited the expression of MMP3 and
MMP13, which was increased by IL-1beta. Finally, we found that pretreatment of GP
obviously suppressed NF-kappaB activation in IL-1beta-stimulated human OA
chondrocytes. Taken together, the results demonstrated that GP has chondro
protective effects, at least in part, through inhibiting the activation of NF
kappaB signaling pathway in human OA chondrocytes. Thus, these findings suggest
that GP may be considered as an alternative therapeutic agent for the management
of OA patients.
PMID- 28422400
TI - Sequence-Specific Covalent Capture Coupled with High-Contrast Nanopore Detection
of a Disease-Derived Nucleic Acid Sequence.
AB - Hybridization-based methods for the detection of nucleic acid sequences are
important in research and medicine. Short probes provide sequence specificity,
but do not always provide a durable signal. Sequence-specific covalent crosslink
formation can anchor probes to target DNA and might also provide an additional
layer of target selectivity. Here, we developed a new crosslinking reaction for
the covalent capture of specific nucleic acid sequences. This process involved
reaction of an abasic (Ap) site in a probe strand with an adenine residue in the
target strand and was used for the detection of a disease-relevant T->A mutation
at position 1799 of the human BRAF kinase gene sequence. Ap-containing probes
were easily prepared and displayed excellent specificity for the mutant sequence
under isothermal assay conditions. It was further shown that nanopore technology
provides a high contrast-in essence, digital-signal that enables sensitive,
single-molecule sensing of the cross-linked duplexes.
PMID- 28422404
TI - Use of resuscitation plans at a tertiary Australian hospital: room for
improvement.
AB - BACKGROUND: The 'Acute Resuscitation Plan' (ARP) is a document for recording the
resuscitation plans of patients at a tertiary hospital for adult patients. The
ARP was introduced at the hospital in September 2014, superseding the 'Not for
Cardiopulmonary Resuscitation (CPR)' form. Unlike the Not for CPR form, the ARP
was relevant to patients with and without resuscitation limits. AIM: To evaluate
the introduction of the ARP. METHODS: This study is a retrospective audit of the
records of all admissions to the hospital from January to June 2014 (Not for CPR
period) and January to June 2015 (ARP period). The main outcomes are the
incidence of resuscitation plans, the proportion of ARP specifying consultation
with the patient (or representative) and with senior medical staff, and the
proportion of ARP among older patients and those with significant comorbidity.
RESULTS: Resuscitation plans were present for 453 of 23 325 (1.9%) admissions in
the Not for CPR period versus 1801 of 24 037 (7.5%) in the ARP period (odds ratio
(OR) 4.1, 95% confidence interval (CI) 3.7-4.5, P < 0.001). A total of 42% of ARP
specified 'care of the dying' in the event of arrest. Acknowledgement of the
views of the patient (or representative) was indicated on 37% of ARP and of a
senior physician on 28%. An ARP was not present for 67% of patients aged >=90
years, 59% from aged care, 90% with metastatic cancer and 64% aged >=80 years and
with a Charlson comorbidity index >=3. CONCLUSIONS: More patients had
resuscitation plans after introducing the ARP. However, patients and senior
physicians were often remote from the consultation process, and an ARP was not
present for many patients likely to have a poor outcome from cardiopulmonary
arrest.
PMID- 28422403
TI - Blood Chimerism in Dizygotic Monochorionic Twins During 5 Years Observation.
AB - Dizygotic monochorionic twin pregnancies can result in blood chimerism due to in
utero twin-to-twin exchange of stem cells. In this case, we examined the
proportion of allogeneic red blood cells by flow cytometry and the proportion of
allogeneic nucleated cells by digital polymerase chain reaction at 7 months and
again at 5 years. We found an increase in the proportion of allogeneic cells from
63% to 89% in one twin, and a similar increase in autologous cells in the other
twin from 57% to 84%. A paradigm for stem cell therapy could be modeled on this
case: induction of tolerance and chimerism by antenatal transfusion of donor stem
cells. The procedure would hold the promise of transplantation and tolerance
induction without myeloablative conditioning for inheritable benign hematological
diseases such as sickle cell disease and thalassemia.
PMID- 28422406
TI - Comparability of three output prediction models for a compact passively double
scattered proton therapy system.
AB - The purpose of this study was to investigate comparability of three output
prediction models for a compact double-scattered proton therapy system. Two
published output prediction models are commissioned for our Mevion S250 proton
therapy system. Model A is a correction-based model (Sahoo et al., Med Phys,
2008;35(11):5088-5097) and model B is an analytical model which employs a
function of r = (R'-M')/M' (Kooy et al., Phys Med Biol, 2005;50:5487-5456) where
R' is defined as depth of distal 100% dose with straggling and M' is the width
between distal 100% dose and proximal 100% dose with straggling instead of the
theoretical definition due to more accurate output prediction. The r is converted
to ((R-0.31)-0.81 * M)/(0.81 * M) with the vendor definition of R (distal 90%
dose) and M (distal 90% dose-to-proximal 95% dose), where R' = R-0.31 (g cm-2 )
and M' = 0.81 * M (g cm-2 ). In addition, a quartic polynomial fit model (model
C) mathematically converted from model B is studied. The outputs of 272 sets of R
and M covering the 24 double scattering options are measured. Each model's
predicted output is compared to the measured output. For the total dataset, the
percent difference between predicted (P) and measured (M) outputs ((P-M)/M *
100%) were within +/-3% using the three different models. The average differences
(+/-standard deviation) were -0.13 +/- 0.94%, -0.13 +/- 1.20%, and -0.22 +/-
1.11% for models A, B, and C, respectively. The p-values of the t-test were 0.912
(model A vs. B), 0.061 (model A vs. C), and 0.136 (model B vs. C). For all the
options, all three models have clinically acceptable predictions. The differences
between models A, B, and C are statistically insignificant; however, model A
generally has the potential to more accurately predict the output if a larger
dataset for commissioning is used. It is concluded that the models can be
comparably used for the compact proton therapy system.
PMID- 28422407
TI - Mutations in TGDS associated with additional malformations of the middle fingers
and halluces: Atypical Catel-Manzke syndrome in a fetus.
AB - Pierre-Robin sequence, radial deviation, and ulnar clinodactyly of the index
fingers due to an additional phalangeal bone, as well as heart defects are the
key features of Catel-Manzke syndrome. Although mutations in TGDS were identified
as the cause of this disorder, the pathogenetic mechanism remains unknown. Here,
we report on a fetus with severe heart defect, nuchal edema, talipes, Pierre
Robin sequence, and bilateral deviation and clinodactyly of the index and middle
fingers. Pregnancy was terminated at the 22nd week of gestation. Postmortem
radiographs showed hypoplasia and V-shaped displacement of the second and third
proximal phalanges of both hands as well as hypoplasia of the first metatarsals
and the phalangeal bones of the halluces. The suggested diagnosis Catel-Manzke
syndrome was confirmed by the detection of two compound heterozygous mutations in
TGDS: The known variant c.298G>T; p.(Ala100Ser) and the so far undescribed
variant c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site
of TGDS. This is the first report on the association of mutations in TGDS with
additional anomalies of the middle fingers and halluces. We provide a detailed
phenotypic characterization of the only fetus with molecularly confirmed Catel
Manzke syndrome, which is relevant for prenatal diagnosis. Our findings widen the
phenotype spectrum caused by TGDS mutations and underline the phenotypic overlap
with Temtamy preaxial brachydactyly syndrome. This improves our understanding of
the prenatal development and the pathogenetic mechanism of Catel-Manzke syndrome.
PMID- 28422408
TI - Prevention of the Osmotic Demyelination Syndrome After Liver Transplantation: A
Multidisciplinary Perspective.
AB - The osmotic demyelination syndrome (ODS) is a serious neurologic condition that
occurs in the setting of rapid correction of hyponatremia. It presents with
protean manifestations, from encephalopathy to the "locked-in" syndrome. ODS can
complicate liver transplantation (LT), and its incidence may increase with the
inclusion of serum sodium as a factor in the Mayo End-Stage Liver Disease score.
A comprehensive understanding of risk factors for the development of ODS in the
setting of LT, along with recommendations to mitigate the risk of ODS, are
necessary. The literature to date on ODS in the setting of LT was reviewed. Major
risk factors for the development of ODS include severe pretransplant hyponatremia
(serum sodium [SNa] < 125 mEq/L), the magnitude of change in SNa pre- versus
posttransplant, higher positive intraoperative fluid balance, and the presence of
postoperative hemorrhagic complications. Strategies to reduce the risk of ODS
include correcting hyponatremia pretransplant via fluid restriction and/or
ensuring an appropriate rate of increase from the preoperative SNa via close
attention to fluid and electrolyte management both during and after surgery.
Multidisciplinary management involving transplant hepatology, nephrology,
neurology, surgery, and anesthesiology/critical care is key to performing LT
safely in patients with hyponatremia.
PMID- 28422409
TI - Validation of the Japanese Version of the Fremantle Back Awareness Questionnaire
in Patients with Low Back Pain.
AB - BACKGROUND: There is a growing interest in the role of disturbed body perception
in people with persistent pain problems such as chronic low back pain (CLBP). A
questionnaire, the Fremantle Back Awareness Questionnaire (FreBAQ), was recently
developed as a simple and quick way of assessing disturbed perceptual awareness
of the back in people with CLBP and appears to have acceptable psychometric
properties. The aim of the present study was to develop a Japanese version of the
FreBAQ (FreBAQ-J) and evaluate its psychometric properties in a sample of
Japanese people with low back pain (LBP). METHODS: Translation of the FreBAQ into
Japanese was conducted using a forward-backward method. One hundred participants
with LBP completed the resultant FreBAQ-J. A subset of the participants completed
the FreBAQ-J again 2 weeks later. Validity was investigated by examining the
relationship between the FreBAQ-J and clinical valuables. Rasch analysis was used
to assess targeting, category ordering, unidimensionality, person fit, internal
consistency, and differential item functioning. RESULTS: The FreBAQ-J was
significantly correlated with pain in motion, disability, pain-related
catastrophizing, fear of movement, and anxiety symptomatology. The FreBAQ-J had
acceptable internal consistency, a minor departure from unidimensionality, and
good test-retest reliability, and was functional on the category rating scale.
CONCLUSIONS: The FreBAQ-J has acceptable psychometric properties and is suitable
for use in people with LBP. Participants with high levels of disturbed body
perception are well targeted by the scale. The functioning of one item (item 8)
was poor. Further study is warranted to confirm if this item should be excluded.
PMID- 28422410
TI - Reply to Comment on the Article "OPTN/SRTR 2015 Annual Data Report: Pancreas".
PMID- 28422411
TI - Optical properties of Eu2+ /Eu3+ mixed valence phosphor Ca2 SiO2 F2 :Eu2+ /Eu3.
AB - The Eu2+ /Eu3+ mixed valence phosphor Ca2 SiO2 F2 :Eu2+ /Eu3+ was prepared using
a solid-state reaction synthesis method in a CO atmosphere, and the optical
properties were investigated. The spectroscopic properties revealed that Ca2+
ions were occupied by both Eu2+ and Eu3+ ions in Ca2 SiO2 F2 , and both ions were
able to generate their characteristic emissions. A broad 5d -> 4f Eu2+ band at
~470 nm and narrow 4f -> 4f Eu3+ peaks upon excitation with n-UV light were
observed. The ratio between Eu2+ and Eu3+ emissions changed regularly, and the
relative intensity of the red component from Eu3+ became systematically stronger
with increasing overall Eu content. As a result, the emission color of these
phosphors can be tunable from blue to pink under n-UV light excitation.
PMID- 28422412
TI - Histological Evolution of BK Virus-Associated Nephropathy: Importance of
Integrating Clinical and Pathological Findings.
AB - Long-term clinicopathological studies of BK-associated nephropathy (PyVAN) are
not available. We studied 206 biopsies (71 patients), followed 3.09 +/- 1.46
years after immunosuppression reduction. The biopsy features (% immunostain for
PyV large T ag + staining and inflammation +/- acute rejection) were correlated
with viral load dynamics and serum creatinine to define the clinicopathological
status (PyVCPS). Incidence of acute rejection was 28% in the second biopsy and
50% subsequently (25% mixed T cell-mediated allograft rejection (TCMR) + antibody
mediated allograft rejection (AMR); rejection overall affected 38% of patients
(>50% AMR). Graft loss was 15.4% (0.8-5.3 years after PyVAN); 76% had complete
viral clearance (mean 28 weeks). The only predictors of graft loss were acute
rejection (TCMR p = 0.008, any type p = 0.07), and increased "t" and "ci" in the
second biopsy (p = 0.006 and 0.048). Higher peak viremia correlated with poorer
viral clearance (p = 0.002). Presumptive and proven PyVAN had similar
presentation, evolution, and outcome. Late PyVAN (>2 years, 9.8%) justifies BK
viremia evaluation at any point with graft dysfunction and/or biopsy evaluation.
This study describes the histological evolution of PyVAN and corresponding
clinicopathological correlations. Although the pathological features overall
reflect the viral and immunological interactions, the PyVAN course remains
difficult to predict based on any single feature. Appropriate clinical management
requires repeat biopsies and determination of the PyVCPS at relevant time points,
for corresponding personalized immunosuppression adjustment.
PMID- 28422413
TI - Essential Oils as Biocides for the Control of Fungal Infections and Devastating
Pest (Tuta absoluta) of Tomato (Lycopersicon esculentum Mill.).
AB - Thymus capitatus and Tetraclinis articulata essential oils as well their major
components (carvacrol and alpha-pinene) were evaluated for their antifungal and
insecticidal activities. Both oils showed good in vitro antifungal activity
against Fusarium oxysporum, Aspergillus niger, Penicillium sp., Alternaria
alternata, and Botrytis cinerea, the fungi causing tomato rot. In vivo results
indicate the efficacies of both essential oils and carvacrol of reduce
postharvest fungal pathogens, such as B. cinerea and Al. alternata that are
responsible of black and gray rot of tomato fruit. Disease incidence of Al.
alternata and B. cinerea decreased on average from 55% to 80% with essential oil
of Th. capitatus and pure carcvacrol, while Te. articulata essential oil
exhibited inhibition of fungal growth of 55% and 25% against Al. alternata and B.
cinerea, respectively, with concentration of 0.4 MUl/l air. The insecticidal
activity of Th. capitatus and Te. articulata essential oils exhibited also a good
insecticidal activity. At the concentration of 0.2 MUl/ml air, the oils caused
mortality over 80% for all larval stages of Tuta absoluta and 100% mortality for
the first-instar after 1.5 h only of exposure. alpha-Pinene presented lower
insecticidal and antifungal activities compared to essential oils of Th.
capitatus, Te. articulata and pure carvacrol. Thus, these essential oils can be
used as a potential source to develop control agents to manage some of the main
pests and fungal diseases of tomato crops.
PMID- 28422415
TI - Impact of hospitalization in an acute geriatric unit on polypharmacy and
potentially inappropriate prescriptions: A retrospective study.
AB - AIM: Polypharmacy is a highly prevalent geriatric syndrome, and hospitalizations
can worsen it. The aim of the present study was to analyze the influence of
hospitalization on polypharmacy and indicators of quality of prescribing, and
their possible association with health outcomes. METHODS: A retrospective study
of 200 patients discharged from an acute geriatric unit was carried out.
Indicators of quality of prescription were registered at admission and discharge:
polypharmacy defined as >=5 medications, hyperpolypharmacy (>=10), potentially
inappropriate prescribing by Beers and Screening Tool of Older Persons'
potentially inappropriate Prescriptions (STOPP) criteria, potentially prescribing
omissions by Screening Tool to Alert doctors to the Right Treatment (START)
criteria, drug interactions and anticholinergic burden measured with the
Anticholinergic Risk Scale. Mortality, emergency room visits and hospital
admissions occurring during 6 months after discharge were also registered.
RESULTS: The total number of drugs increased at discharge (9.1 vs 10.1, P <
0.001), without increasing chronic medications (8.5 vs 8.3, P = 0.699). No
significant variations were observed in the prevalence of polypharmacy (86.5% vs
82.2%), potentially inappropriate prescribing (68.5% vs 71.5%), potential
prescribing omissions (58% vs 58%) or drug interactions (82.5% vs 83.5%).
Patients with anticholinergic drugs tended to increase, not reaching statistical
significance (39.5% vs 44.5%; P = 0.064). Polypharmacy was associated with
emergency room visits (OR 2.62, 95% CI 1.07-6.40; P = 0.034), and
hyperpolypharmacy with hospitalizations (OR 2.49, 95% CI 1.25-4.93; P = 0.009).
CONCLUSIONS: After hospitalization in an acute geriatric unit, the prevalence of
polypharmacy, potentially inappropriate prescribing, potential prescribing
omissions, interactions or anticholinergic drugs is still very high. Polypharmacy
is a risk factor for hospitalization and emergency room visits. Measuring
indicators of quality of prescription might be useful to design interventions to
optimize pharmacotherapy and improve health outcomes in elderly acute patients.
Geriatr Gerontol Int 2017; 17: 2354-2361.
PMID- 28422416
TI - Clot wave analysis and thromboembolic score in liver cirrhosis: two opposing
phenomena.
AB - INTRODUCTION: Prothrombin time (PT) and activated partial thromboplastin time
(aPTT) are abnormal but unreliable in cirrhotic patients to express their risk of
bleeding. However, these patients may also suffer from thrombotic episodes. In
order to investigate the dynamics of the formation of fibrin, the clot waveform
analysis (CWA) of aPTT was studied together with a score for the evaluation of
the thromboembolic risk. METHODS: CWA in terms of velocity (1st derivative),
acceleration (2nd derivatives) and density (Delta) of aPTT and the Padua
Prediction Score (PPS) for venous thromboembolism were studied in 191 cirrhotic
patients. RESULTS: CWA values were lower in the cirrhotic patients when compared
to the control groups. However, Delta, 1st and 2nd derivatives were higher in
cirrhotic patients with elevated PPS in comparison to those with a low PPS. The
1st derivative was significantly associated with a high PPS score (>4): OR: 2.66,
CI: 95% 1.23-5.78. CONCLUSIONS: Two opposing tendencies seem to be present in
cirrhotic disease: the first shows a weakness of clot formation while the second
a predisposition towards thrombosis, identified by the PPS.
PMID- 28422417
TI - Cranial irradiation in childhood mimicking neurofibromatosis type II.
AB - Neurofibromatosis type II (NF2) is a genetic disease characterized by bilateral
vestibular schwannomas (VS) and other nerve system tumors. However, such tumors
may be associated with environmental, rather than a genetic, etiology.
Individuals fulfilling the clinical criteria of NF2 who had been treated by head
ionized irradiation at a young age were compared for disease characteristics and
molecular analysis with non-irradiated sporadic NF2 cases. In the study cohort,
three of 33 sporadic adult cases fulfilling NF2 diagnostic criteria had a history
of early age cranial irradiation exposure. None of the irradiated patients had
bilateral VS compared with 73.3% of the non-irradiated individuals. One of the
irradiated patients had no VS, while none of the non-irradiated NF2 cases had
absence of VS. All of the irradiated individuals had brain meningiomas and
thyroid tumors compared with 47% and 0%, respectively, of the non-irradiated
individuals. Molecular analyses for NF2 mutations in blood of the irradiated
individuals failed to detect disease-causing mutations. This study suggest that
environmental factors may mimic NF2. Identifying such non-genetic cases
fulfilling clinical criteria of the genetic disease may be crucial for the
purposes of genetic counseling and patient management.
PMID- 28422418
TI - Factors associated with mucosal dryness in multiple regions and skin: A web-based
study in women.
AB - AIM: We hypothesized that feeling mucosal dryness in one body region and the skin
may be associated with dryness in other regions and that there are common
background factors for dryness. In an earlier web-based survey, we reported
prevalence figures of dry eyes, nose, mouth, skin, and vagina. In the present
study, additional analyses were made to investigate the factors associated with
dryness in each region, and simultaneous dryness in multiple regions. METHODS: A
web-based questionnaire was completed by 310 Japanese women. The questions
included dryness of the eyes, nose, mouth, vagina, and skin. Menopausal and other
symptoms were also addressed. Multiple logistic regression modeling was performed
to identify factors associated with dryness in each region and in multiple dry
regions. RESULTS: Dry eyes were associated with dryness in the nose and with
headache; dry nose was associated with dryness in the vagina and eyes; dry mouth
was associated with sticky mouth symptom and dryness of the nose; dry skin was
associated with use of xerogenic medications and vaginal discharge; and dryness
of the vagina was associated with vaginal itchiness and dry nose. Vaginal
discharge (odds ratio, 9.64; 95% confidence interval, 3.15-29.51) and sticky
mouth (odds ratio, 6.35; 95% confidence interval, 1.29-31.29) were further
associated with dryness in multiple regions. CONCLUSION: The present results
confirmed our study hypothesis by showing that dryness in one region was clearly
associated with that in another or in multiple regions. The result implies the
need for holistic diagnosis and counseling for patients with dryness complaints.
PMID- 28422419
TI - Carbohydrate Analogue Microarrays for Identification of Lectin-Selective Ligands.
AB - Fifty-five mono- and disaccharide analogues were prepared and used for the
construction of microarrays to uncover lectin-selective ligands. The microarray
study showed that two disaccharide analogues, 28' and 44', selectively bind to
Solanum tuberosum lectin (STL) and wheat germ agglutinin (WGA), respectively.
Cell studies indicated that 28' and 44' selectively block the binding of STL and
WGA to mammalian cells, unlike the natural ligand LacNAc, which suppresses
binding of both STL and WGA to cells.
PMID- 28422420
TI - A study of disseminated intravascular coagulation in acute leukemia reveals
markedly elevated D-dimer levels are a sensitive indicator of acute promyelocytic
leukemia.
AB - INTRODUCTION: While the presence of disseminated intravascular coagulation (DIC)
has been implicated in worse clinical outcome in acute leukemia, the relationship
between different subtypes of acute leukemia and the clinicopathologic features
of DIC has not been systematically well studied. METHODS: In this study, we
retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed
the utility of evaluating red blood cell morphologic features, and coagulation
parameters in determining the presence of DIC as well as differentiating subtypes
of acute leukemia. RESULTS: Review of our cohort demonstrates a novel finding,
that elevated D-dimer concentrations >=19 000 ng/mL fibrinogen equivalent units
(FEU) are a sensitive diagnostic indicator of acute promyelocytic leukemia (APL)
with moderate specificity, sensitivity 96%, specificity 92% in acute leukemia
subtyping. Similar to other studies, APL showed an increased incidence of DIC (P
< 0.01) compared to other subtypes of acute leukemia. Surprisingly, the presence
of schistocytes on the peripheral blood smear was not a statistically significant
indicator of DIC, sensitivity of 36% and specificity of 89%. Finally, the
presence of DIC was not a significant indicator of poorer prognosis amongst all
patients with AML. CONCLUSION: Overall we identify elevated D-dimer
concentrations >=19 000 ng/mL FEU are a sensitive indicator of acute
promyelocytic leukemia (APL), with a sensitivity of 96% and specificity of 92% in
the subtyping of acute leukemias, and that the presence of schistocytes in
peripheral blood smears is not a diagnostically sensitive screening test for DIC
with a sensitivity of 36%.
PMID- 28422421
TI - Results of a 10-year survey of workload for 10 treatment vaults at a high
throughput comprehensive cancer center.
AB - The workload for shielding purposes of modern linear accelerators (linacs)
consists of primary and scatter radiation which depends on the dose delivered to
isocenter (cGy) and leakage radiation which depends on the monitor units (MUs).
In this study, we report on the workload for 10 treatment vaults in terms of dose
to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions
(Txs), as well as, use factors (U) and modulation factors (CI) for different
treatment techniques. The survey was performed for the years between 2006 and
2015 and included 16 treatment machines which represent different generations of
Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at
different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6
and 15 MV x-rays). An institutional review board (IRB) approval was acquired to
perform this study. Data regarding patient workload, dose to isocenter, number of
monitor units delivered, beam energies, gantry angles, and treatment techniques
were exported from an ARIA treatment management system (Varian Medical Systems,
Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in
Matlab. The average (+/- std-dev) number of treatment sessions, dose to
isocenter, and number of monitor units delivered per week per machine in 2006 was
119 +/- 39 Txs, (300 +/- 116) * 102 cGys, and (78 +/- 28) * 103 MUs respectively.
In contrast, the workload in 2015 was 112 +/- 40 Txs, (337 +/- 124) * 102 cGys,
and (111 +/- 46) * 103 MUs. 60% of the workload (cGy) was delivered using 6 MV
and 30% using 15 MV while the remaining 10% was delivered using electron beams.
The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (+/- 3.4) and 4.6 (+/-
1.6) respectively. Use factors using 90 degrees gantry angle intervals were
equally distributed (~0.25) but varied considerably among different treatment
techniques. The workload, in terms of dose to isocenter (cGy) and subsequently
monitor units (MUs), has been steadily increasing over the past decade. This
increase can be attributed to increased use of high dose hypo-fractionated
regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require
higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile,
the patient workload in terms of treatment sessions per week remained relatively
constant. The findings of this report show that variables used for shielding
purposes still fall within the recommendation of NCRP Report 151.
PMID- 28422422
TI - Psychopathology and social functioning of 42 subjects from a Danish ultra high
risk cohort.
AB - AIM: To make a thorough characterization of the co-morbidity, psychopathology and
demographics in the first Danish ultra high-risk (UHR) sample. METHOD: Forty-two
UHR subjects went through comprehensive interviews assessing their
psychopathology, psychiatric disorders, substance use and family history of
psychiatric disorders. RESULTS: All UHR subjects met the criteria of at least 1
axis I diagnosis in the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) and met on average four diagnoses (both axis I and II),
mostly within the areas of depression, anxiety and substance abuse. A total of
48% had schizotypal personality disorder and 19% had borderline personality
disorder. Level of functioning was low with a mean score on the Social and
Occupational Functioning Assessment Scale corresponding to "major impairment in
several areas," and mean scores in the Global Functioning: Social and Role scales
between "moderate impairment in social functioning" and "very serious impairment
independently." Forty-seven percent were unemployed and 29% on sick leave. Fifty
five percent relied financially on public support. CONCLUSION: As seen in
previous UHR populations, Danish UHR subjects had low function socio-economically
and met criteria of several psychiatric diagnoses, suggesting that they require
pharmacological and non-pharmacological psychiatric treatment as well as
vocational and educational guidance and support.
PMID- 28422423
TI - Erratum.
PMID- 28422424
TI - Pregnancy outcomes in women with different doses of corticosteroid
supplementation during labor and delivery.
AB - AIM: The aim of this study was to report the pregnancy outcomes of women who
received different doses of corticosteroid supplementation during labor and
delivery. METHODS: We conducted a retrospective review of 102 pregnant women who
received oral corticosteroid therapy, delivered at Osaka University Hospital, and
were administered intravenous corticosteroid supplementation during labor and
delivery. From January 2008 to May 2012, 47 women were administered a high dose
of corticosteroids (HD group). From June 2012 to December 2016, 55 women were
given a low dose of corticosteroids (LD group). RESULTS: There were no
significant differences in the patient characteristics between the two groups.
The most frequent disease was systemic lupus erythematosus (30/102; 29.4%). Most
women used prednisolone for more than 1 year (91/102; 89.2%) and at a dose of
more than 5 mg/day (88/102; 86.3%). The total intravenous dose of hydrocortisone
during labor and delivery +/- standard deviation was 233.5 +/- 129.4 mg (HD
group) and 143.4 +/- 38.1 mg (LD group), exhibiting a significantly larger dose
in the HD group. No patients suffered an adrenal deficiency and there were no
significant differences in the hemodynamics. There were three cases of puerperal
endometritis, two patients with hyperglycemia, and one wound infection in the HD
group, whereas one case of puerperal endometritis in the LD group. There were no
significant differences in the neonatal outcomes. CONCLUSION: Pregnancy outcomes
did not differ between the high and low doses of corticosteroid supplementation
during labor and delivery.
PMID- 28422425
TI - Negativization of viremia prior to liver transplant reduces early allograft
dysfunction in hepatitis C-positive recipients.
AB - Although early allograft dysfunction (EAD) negatively impacts survival from the
first months following liver transplantation (LT), direct-acting antiviral agents
(DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the
EAD definition best predicting 90-day graft loss and identified EAD risk factors
in HCV-positive recipients. From November 2002 to June 2016, 603 HCV-positive
patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV-negative
donors. The median recipient Model for End-Stage Liver Disease (MELD) score was
15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV
RNA negative; negativization was achieved and maintained by pre-LT antiviral
therapy (61 patients) or pre-LT plus a pre-emptive post-LT course (16 patients);
60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3
different EAD definitions: (1) bilirubin >= 10 mg/dL or international normalized
ratio >= 1.6 on day 7 after LT or aspartate aminotransferase or alanine
aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on
days 2-7 after LT; and (3) MELD >= 19 on day 5 after LT. EAD defined by MELD >=
19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9)
likelihood ratio to predict 90-day graft loss. At 90 days after LT, 9.2% of
recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P <
0.001). At multivariate analysis, considering variables available at LT, MELD at
LT of >25 (OR = 7.4) or 15-25 (OR = 3.2), graft macrovesicular steatosis >= 30%
(OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0),
earlier LT era (OR = 1.8), and cold ischemia time >= 8 hours (OR = 1.8) were
significant risk factors for EAD. In conclusion, in HCV-positive patients, MELD
>= 19 on day 5 after LT best predicts 90-day graft loss. Preventing graft
infection by pre-/peri-LT antiviral therapy reduces EAD incidence and could be
most beneficial in high-MELD patients and recipients of suboptimal grafts. Liver
Transplantation 23 915-924 2017 AASLD.
PMID- 28422426
TI - Dinosaurs, Chameleons, Humans, and Evo-Devo Path: Linking Etienne Geoffroy's
Teratology, Waddington's Homeorhesis, Alberch's Logic of "Monsters," and
Goldschmidt Hopeful "Monsters".
AB - Since the rise of evo-devo (evolutionary developmental biology) in the 1980s, few
authors have attempted to combine the increasing knowledge obtained from the
study of model organisms and human medicine with data from comparative anatomy
and evolutionary biology in order to investigate the links between development,
pathology, and macroevolution. Fortunately, this situation is slowly changing,
with a renewed interest in evolutionary developmental pathology (evo-devo-path)
in the past decades, as evidenced by the idea to publish this special, and very
timely, issue on "Developmental Evolution in Biomedical Research." As all of us
have recently been involved, independently, in works related in some way or
another with evolution and developmental anomalies, we decided to join our
different perspectives and backgrounds in the present contribution for this
special issue. Specifically, we provide a brief historical account on the study
of the links between evolution, development, and pathologies, followed by a
review of the recent work done by each of us, and then by a general discussion on
the broader developmental and macroevolutionary implications of our studies and
works recently done by other authors. Our primary aims are to highlight the
strength of studying developmental anomalies within an evolutionary framework to
understand morphological diversity and disease by connecting the recent work done
by us and others with the research done and broader ideas proposed by authors
such as Etienne Geoffroy Saint-Hilaire, Waddington, Goldschmidt, Gould, and Per
Alberch, among many others to pave the way for further and much needed work
regarding abnormal development and macroevolution.
PMID- 28422427
TI - Is motor imagery different in catatonic schizophrenia?
AB - Catatonic schizophrenia, a rare subtype in this disease group, is characterized
by motor disturbances. The current study investigated the reactivity of
electroencephalographic mu rhythm in a motion imagery task in two single cases of
first-episode catatonic schizophrenia, assuming they would show less mu rhythm
reduction compared to paranoid schizophrenic patients and healthy controls.
PMID- 28422428
TI - Identification of Transthyretin Fibril Formation Inhibitors Using Structure-Based
Virtual Screening.
AB - Transthyretin (TTR) is the primary carrier for thyroxine (T4 ) in cerebrospinal
fluid and a secondary carrier in blood. TTR is a stable homotetramer, but certain
factors, genetic or environmental, could promote its degradation to form amyloid
fibrils. A docking study using crystal structures of wild-type TTR was planned;
our aim was to design new ligands that are able to inhibit TTR fibril formation.
The computational protocol was thought to overcome the multiple binding modes of
the ligands induced by the peculiarity of the TTR binding site and by the
pseudosymmetry of the site pockets, which generally weaken such structure-based
studies. Two docking steps, one that is very fast and a subsequent step that is
more accurate, were used to screen the Aldrich Market Select database. Five
compounds were selected, and their activity toward inhibiting TTR fibril
formation was assessed. Three compounds were observed to be actives, two of which
have the same potency as the positive control, and the other was found to be a
promising lead compound. These results validate a computational protocol that is
able to archive information on the key interactions between database compounds
and TTR, which is valuable for supporting further studies.
PMID- 28422430
TI - AAPM Spring Clinical Meeting - Abstracts.
PMID- 28422429
TI - Development of the headspace Family and Friends Satisfaction Scale: Findings from
a pilot study.
AB - AIMS: The primary aim of this pilot study was to determine the psychometric
properties of the 18-item headspace Family and Friends Satisfaction Scale
(hFAFSS). METHODS: During August 2015, staff from 22 headspace centres approached
family members and friends of young people attending headspace to complete the
hFAFSS. Principal components analysis with oblique Promin rotation and polychoric
correlations were used to assess the factor structure of the hFAFSS. RESULTS:
There were 277 usable responses. Satisfaction was high, resulting in little
variance. Parallel analyses suggested that the scale items tapped a single factor
(68% of variance). CONCLUSIONS: This study is one of the first attempts to
measure the satisfaction of family and friends with primary care-based youth
mental health services. Satisfaction of family members and friends was shown to
be high, but limited variance restricts the usability of the hFAFSS as an
evaluation measure, and revision and further testing is needed.
PMID- 28422431
TI - Effect of Empagliflozin on Tacrolimus-Induced Pancreas Islet Dysfunction and
Renal Injury.
AB - An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in
type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus
(TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced
pancreatic islet dysfunction and renal injury in an experimental model of TAC
induced DM and in vitro. TAC induced a twofold increase in SGLT-2 expression,
while Em decreased SGLT-2 expression and further increased urinary glucose
excretion compared to the TAC group. Em reduced hyperglycemia and increased
plasma insulin level, pancreatic islet size, and glucose-stimulated insulin
secretion compared to the TAC group. In kidney, Em alleviated TAC-induced renal
dysfunction and decreased albumin excretion and histological injury compared with
the TAC group. Increased oxidative stress and apoptotic cell death by TAC was
remarkably decreased with Em in serum and pancreatic and renal tissues. In in
vitro study, TAC decreased cell viability and increased reactive oxygen species
(ROS) production in both insulin-secreting beta-cell derived (INS-1) and human
kidney-2 (HK-2) cell lines. Addition of Em increased cell viability and decreased
ROS production in HK-2 but not in INS-1 cell lines. This suggests that Em is
effective in controlling TAC-induced hyperglycemia and has direct protective
effect on TAC-induced renal injury.
PMID- 28422432
TI - JA but not JA-Ile is the cell-nonautonomous signal activating JA mediated
systemic defenses to herbivory in Nicotiana attenuata.
AB - The whole-plant activation of defense responses to wounding and herbivory
requires systemic signaling in which jasmonates (JAs) play a pivotal role. To
examine the nature of the slower cell-nonautonomous as compared to the rapid cell
autonomous signal in mediating systemic defenses in Nicotiana attenuata,
reciprocal stem grafting-experiments were used with plants silenced for the JA
biosynthetic gene ALLENE OXIDE CYCLASE (irAOC) or plants transformed to create JA
sinks by ectopically expressing Arabidopsis JA-O-methyltransferase (ovJMT). JA
impaired irAOC plants were defective in the cell-nonautonomous signaling pathway
but not in JA transport. Conversely, ovJMT plants abrogated the production of a
graft-transmissible JA signal. Both genotypes displayed unaltered cell-autonomous
signaling. Defense responses (17-hydroxygeranyllinalool diterpene glycosides,
nicotine, and proteinase inhibitors) and metabolite profiles were differently
induced in irAOC and ovJMT scions in response to graft-transmissible signals from
elicited wild type stocks. The performance of Manduca sexta larvae on the scions
of different graft combinations was consistent with the patterns of systemic
defense metabolite elicitations. Taken together, we conclude that JA and possibly
MeJA, but not JA-Ile, either directly functions as a long-distance transmissible
signal or indirectly interacts with long distance signal(s) to activate systemic
defense responses.
PMID- 28422433
TI - Rigid Nonfullerene Acceptors Based on Triptycene-Perylene Dye for Organic Solar
Cells.
AB - Three kinds of nonconjugated rigid perylene bisimide (PBI) derivatives based on a
triptycene core were designed, synthesized and characterized. The unique three
dimensional (3D) conformation of triptycene could enable formation of polymer
with the favorable morphology for organic polymer solar cells (PSCs) by relieving
the self-aggregation of rigid PBI units. The low-lying LUMO energy levels of
these compounds demonstrated that they are very suitable for use as acceptors in
organic solar cells. A higher power conversion efficiency (PCE) of 6.15 % was
obtained for the blend film using the compound with two PBI units (T-2) as the
acceptor and commercial poly[[4,8-bis[5-(2-ethylhexyl)thiophene-2-yl]benzo[1,2
b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4
b]thiophenediyl]] (PCE-10) as the electron donor.
PMID- 28422434
TI - Rat Hindlimb Cryopreservation and Transplantation: A Step Toward "Organ Banking".
AB - In 2016, over 5 million reconstructive procedures were performed in the United
States. The recent successes of clinical vascularized composite
allotransplantations, hand and face transplantations included, established the
tremendous potential of these life-enhancing reconstructions. Nevertheless, due
to limited availability and lifelong immunosuppression, application is limited.
Long-term banking of composite transplants may increase the availability of
esthetically compatible parts with partial or complete HLA matching, reducing the
risk of rejection and the immunosuppressive burden. The study purpose was to
develop efficient protocols for the cryopreservation and transplantation of a
complete rodent limb. Directional freezing is a method in which a sample is
cooled at a constant-velocity linear temperature gradient, enabling precise
control of the process and ice crystal formation. Vitrification is an alternative
cryopreservation method in which the sample solidifies without the formation of
ice crystals. Testing both methods on a rat hindlimb composite tissue
transplantation model, we found reliable, reproducible, and stable ways to
preserve composite tissue. We believe that with further research and development,
cryopreservation may lead to composite tissue "banks." This may lead to a
paradigm shift from few and far apart emergent surgeries to wide-scale, well
planned, and better-controlled elective surgeries.
PMID- 28422435
TI - Blue organic light-emitting diodes based on fluorene-bridged quinazoline and
quinoxaline derivatives.
AB - Two blue emitters based on fluorene-bridged quinazoline and quinoxaline
derivatives were prepared via the Suzuki reaction. Their photoluminescent
properties were investigated. Furthermore, theoretical studies on these materials
using the density functional theory calculation were conducted. To explore their
electroluminescent properties, multilayered organic light-emitting diodes were
fabricated with the following device structure: indium-tin-oxide (180 nm)/4,4'
bis(N-(1-naphthyl)-N-phenylamino)biphenyl (50 nm)/blue emitting materials (1 and
2) (30 nm)/bathophenanthroline (35 nm)/8-hydroxy-quinolinato lithium (2 nm)/Al
(100 nm). Two devices showed efficient blue emission with the external quantum
efficiencies of 1.58% and 1.30%, respectively, at 20 mA/cm2 , and Commission
Internationale dEclairage coordinates of (0.18, 0.24) and (0.19, 0.27) at 6.0 V.
These results suggest that the self-aggregation properties of emitters would have
considerable effects on their photoluminescent and electroluminescent properties.
PMID- 28422437
TI - Prognostic value of Hutchinson's sign for ocular involvement in herpes zoster
ophthalmicus.
PMID- 28422436
TI - Tandem Transformation of Nitro Compounds into N-Methylated Amines: Greener
Strategy for the Utilization of Methanol as a Methylating Agent.
AB - A simple air- and moisture-stable, highly efficient ruthenium NNN pincer complex
is reported for the first time to catalyze the tandem transformation of various
aromatic and aliphatic nitro compounds into the corresponding N-methylated amines
in up to 98 % yield by using methanol as a green methylating agent. Gram-scale
reactions of challenging nitro substrates demonstrated the practical application
aspects of this catalytic system. Importantly, the N-methylamine moiety could be
smoothly introduced to various complex molecular structures without using any
expensive palladium/phosphine/amine-based cross-coupling reactions.
PMID- 28422439
TI - Does touch inhibit visual imagery? A case study on acquired blindness.
AB - In a single-case study of acquired blindness, differential brain activation
patterns for visual imagery of familiar objects with and without tactile
exploration as well as of tactilely explored unfamiliar objects were observed.
Results provide new insight into retrieval of visual images from episodic memory
and point toward a potential tactile inhibition of visual imagery.
PMID- 28422440
TI - Blood parameters of preterm neonates: postnatal evolution according to
gestational age.
AB - INTRODUCTION: The blood count provides qualitative and quantitative essential
information on bloodlines. Reference hematologic parameters have been established
in children and neonates, but few data are available regarding the premature
population during the first month of life. The main objective of this study was
to establish normative values for blood parameters for premature infants born
between 26 and <37 weeks of gestation, during the first month of life, taking
into account gestational and postnatal age and treatments that can impact the
threshold values. METHODS: A single-center retrospective study was conducted
based on the clinical and laboratory data of preterm infants born between January
1, 2012 and December 31, 2013 and hospitalized in the intensive care, neonatal,
and maternity units of University Hospital of Saint Etienne (France). Data were
collected by crossing the PMSI database (date of birth and gestational age), the
administrative patient database (IPP), and the pre-analytical laboratory
database. Anthropometric and clinical data were extracted for both mother and
child. The samples were all made from central or peripheral venous blood. All
blood parameters were taken into account. RESULTS: The degree of prematurity is a
factor greatly influencing the values of the blood parameters at birth. All three
blood lines increase in proportion to gestational age. We were able to highlight
for some blood parameters specific kinetic profiles according to gestational age.
CONCLUSION: Blood parameters of preterm neonates depend on both the degree of
prematurity, postnatal age, and perinatal treatments. A good knowledge of these
physiological variations may help target transfusion or therapeutic indications
in everyday practice.
PMID- 28422438
TI - Moyamoya syndrome in children with neurofibromatosis type 1: Italian-French
experience.
AB - Moyamoya syndrome (MMS) is the most common cerebral vasculopathy among children
with neurofibromatosis type 1 (NF1). In this study, we clinically,
radiologically, and genetically examined a cohort that was not previously
described, comprising European children with NF1 and MMS. The NF1 genotyping had
been registered. This study included 18 children. The mean age was 2.93 +/- 3.03
years at the NF1 diagnosis and 7.43 +/- 4.27 years at the MMS diagnosis. In seven
patients, MMS was diagnosed before or at the same time as NF1. Neuroimaging was
performed in 10 patients due to clinical symptoms, including headache (n = 6),
cerebral infarction (n = 2), and complex partial seizures (n = 2). The remaining
eight children (47%) had MMS diagnosed incidentally. Sixteen children were
characterized molecularly. The features of MMS were similar between patients with
and without NF1. Additionally, the NF1 phenotype and genotype were similar
between children with and without MMS. Interestingly, three children experienced
tumors with malignant histology or behavior. The presence of two first cousins in
our cohort suggested that there may be potential genetic factors, not linked to
NF1, with an additional role respect of NF1 might play a role in MMS
pathogenesis. The incidental diagnosis of MMS, and the observation that, among
children with NF1, those with MMS were clinically indistinguishable from those
without MMS, suggested that it might be worthwhile to add an angiographic
sequence to brain MRIs requested for children with NF1. A MMS diagnosis may
assist in properly addressing an NF1 diagnosis in very young children who do not
fulfill diagnostic criteria.
PMID- 28422441
TI - Recent Advances of Electrospun Nanofibrous Membranes in the Development of
Chemosensors for Heavy Metal Detection.
AB - It is critical to detect and analyze the heavy metal pollutions in environments
and foods. Chemosensors have been widely investigated for fast detection of
analytes such as heavy metals due to their unique advantages. In order to improve
the detection sensitivity of chemosensors, recently electrospun nanofibrous
membranes (ENMs) have been explored for the immobilization of chemosensors or
receptors due to their high surface-to-volume ratio, high porosity, easiness of
fabrication and functionalization, controllability of nanofiber properties, low
cost, easy detection, no obvious pollution to the detection solution, and easy
post-treatment after the detection process. The purpose of this review is to
summarize and guide the development and application of ENMs in the field of
chemosensors for the detection of analytes, especially heavy metals. First, heavy
metals, chemosensors, and four types of preparation methods for ENM-immobilized
chemosensors/receptors are briefly introduced. And then, ENM-immobilized
chemosensors/receptors and their application progresses for optical, electro, and
mass detections of heavy metals are reviewed according to the four types of
preparation methods. Finally, the application of ENM-immobilized
chemosensors/receptors is summarized and an outlook is provided. The review will
provide an instruction to the research and development of ENM-immobilized
chemosensors/receptors for the detection of analytes.
PMID- 28422442
TI - Effect of hepatitis B virus subgenotype on antiviral response in nucleoside
treated hepatitis B envelope antigen-positive patients.
AB - AIM: Previous studies have reported that hepatitis B virus (HBV) genotype is not
a predictor of treatment response with nucleos(t)ide analog therapy. However, the
impact of subgenotype on treatment response is unknown. The aim of this study is
to identify the effect of HBV subgenotype on treatment response. METHODS: In this
retrospective study, the derivation dataset comprised patients from the EFFORT
study (NCT00962533) telbivudine monotherapy group; patients infected with
genotypes B or C from the GLOBE (NCT00057265) and 015 (NCT00131742) studies
formed the validation dataset. The HBV subgenotypes were determined using
phylogenetic analysis based on the surface or overlapping polymerase gene.
Molecular modeling was used to investigate relationships between positions of the
substitutions within reverse transcriptase and genotypic resistance. RESULTS: Of
the patients in the derivation dataset, 110, 24, 162, and 1 patients were
classified as having HBV subgenotypes B2, C1, C2, or other, respectively,
compared to 222, 146, 282, and 51 in the validation dataset, respectively.
Patients infected with subgenotype C1 showed a higher virologic response rate and
hepatitis B envelope antigen seroconversion rate, and lower genotypic resistance
rate than those infected with subgenotypes B2 and C2. Patients with genotypic
resistance to telbivudine with subgenotype C1 showed fewer secondary mutations.
The crystal structure model of reverse transcriptase showed that these secondary
mutations were located around the YMDD motif, which possibly influenced the
chance of mutations at rtM204. CONCLUSION: Hepatitis B virus subgenotype C1 is
associated with better antiviral response to nucleoside analogs in hepatitis B
envelope antigen-positive patients than B2 and C2 subgenotypes. The exact
mechanism needs to be explored further.
PMID- 28422443
TI - Role of CD200 in differential diagnosis of mature B-cell neoplasm.
AB - INTRODUCTION: CD 200 is a type I immunoglobulin super family membrane
glycoprotein, which is expressed in various mature B-cell neoplasm (MBN). This
study aimed at analyzing the expression pattern of CD200 by flow cytometry
immunophenotyping (FCI) and to evaluate its utility in narrowing down the
differential diagnosis of MBN, particularly in low-grade lymphomas. METHODS: A
total of 160 samples were evaluated by FCI over a period of 2 years (July 2014
June 2016), by a panel of antibodies including CD200. The mean fluorescence
intensity (MFI) of CD200 in the neoplastic population was noted and compared
among several groups of MBN. RESULTS: All the 98 cases of chronic lymphocytic
leukemia (CLL), five being CD23-negative, expressed CD200 with moderate-to-bright
intensity (median MFI: 1174). None of the 24 mantle cell lymphoma (MCL) cases,
two being CD23-positive, expressed CD200 (median MFI: 10). All six hairy cell
leukemia (HCL) cases expressed CD200. CD200 expression in HCL was brightest among
all the MBNs, with a median MFI of 5050. Other MBN (n = 32) expressed CD200 in a
proportion of cases and with variable intensity, usually dimmer than CLL.
CONCLUSION: CD200 has a valid role in differentiating CLL from MCL, especially in
the cases with immunophenotypic overlap. HCL has a consistent and brightest
expression of CD200. It would be prudent to include CD200 in the primary panel of
antibodies for MBN analysis.
PMID- 28422444
TI - Validation of the Mandarin Chinese Version of the Pain Sensitivity Questionnaire.
AB - BACKGROUND AND AIM: The Pain Sensitivity Questionnaire (PSQ), a self-reported
scale, has been used to assess the pain sensitivity level in a Caucasian
population. However, a validated Mandarin Chinese version of the PSQ is not
available. This study was aimed to translate the PSQ into Mandarin Chinese (PSQ
C) and validate it to measure pain sensitivity among Chinese people. METHODS: The
English version of the PSQ has been translated into Mandarin Chinese (PSQ-C),
according to the standard steps of cross-cultural adaptation of self-reported
scales. Three of the 17 items were revised owing to cultural adaptation. The
final version was validated on a population of 182 Chinese people in Changsha
City, China, during October to December 2015. The participants underwent
electrical experimental pain testing. The psychometric properties of the PSQ-C
and its subscales were examined. RESULTS: The Cronbach's alpha coefficients for
the PSQ-C-total, PSQ-C-moderate, and PSQ-C-minor were 0.90, 0.86, and 0.81,
respectively. Acceptable test-retest reliability, content validity, and construct
validity were demonstrated. Concurrent validity was shown via significant
positive correlations between PSQ-C scores and perceived pain intensity at pain
threshold and during pain stimulation with a fixed intensity. Convergent validity
was shown via significant positive correlations between Pain Catastrophizing
Scale scores and PSQ-C scores. Known group validity was demonstrated via higher
PSQ-C-total and PSQ-C-moderate scores among those with high neuroticism scores.
These results indicate that the PSQ-C has reasonably good psychometric
properties, similar to the original English and German versions. CONCLUSION: The
PSQ-C is a reliable and useful tool to assess pain sensitivity levels in a
Chinese population.
PMID- 28422445
TI - Transcriptional profiling of SHR/NCrl prefrontal cortex shows hyperactivity
associated genes responsive to amphetamine challenge.
AB - Several studies suggest a strong genetic component of attention
deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder
characterized by inappropriate levels of hyperactivity, impulsivity and
inattention. Determining specific genetic risk variants for each symptom
dimension of ADHD may aid in the identification of the biological risk factors of
the disorder. In this study, we explored the potential genetic underpinnings of
the hyperactive phenotype of ADHD. To this end, we examined differentially
expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal
model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat
and the Wistar rat, strain used to represent the 'normal' heterogeneous
population. Relative to WKY/NCrl and Wistar controls, SHR/NCrl showed
hyperactivity in the open-field test. Treatment with the ADHD drug, amphetamine
(AMPH) reduced hyperactivity in SHR/NCrl. Meanwhile, AMPH increased locomotor
activity in WKY/NCrl and Wistar rats. Gene expression analysis found 21 common
upregulated and 36 downregulated genes in the PFC of drug-naive SHR/NCrl when
compared with WKY/NCrl and Wistar rats. Of these DEGs, expression levels of two
genes, Atxn7 and Per2, which are involved in transcription and circadian rhythm,
respectively, were downregulated following AMPH treatment in SHR/NCrl.
Quantitative real-time-polymerase chain reaction analyses verified expression
patterns of these genes in the PFC of drug-naive and AMPH-treated SHR/NCrl. The
present findings indicate genetic risk variants that may be associated with the
hyperactive phenotype in ADHD. Further studies are warranted to establish the
roles of Atxn7 and Per2 in mediating hyperactivity.
PMID- 28422446
TI - Fusion of a family 20 carbohydrate-binding module (CBM20) with cyclodextrin
glycosyltransferase of Geobacillus sp. CHB1 improves catalytic efficiency.
AB - Cyclodextrin glycosyltransferase (CGTase) is an important industrial enzyme for
production of cyclodextrins (CDs) from starch by intramolecular
transglycosylation. CGTase consists of five domains labeled A to E. For
optimizing catalytic activity of CGTase, CGTase of Geobacillus sp. was fused with
the family 20 carbohydrate-binding module (CBM) of the Bacillus circulans strain
251 CGTase. The CBMbc251 that has a low binding free energy with maltohexaose,
was selected by in silico design. Then the fusion enzyme, CGTDeltaE-CBMbc251, was
constructed by fusing the CBMbc251 to the C-terminal region of CGTDeltaE. The
fusion enzyme displayed an even greater enhancement of total alpha-cyclization
activity (40.2%) and gamma-cyclization activity (181.58%). Optimal reaction pH
range was wilder and the thermal stability was better under 50 and 60 degrees C.
Compared to the wild-type CGTase, the fusion enzyme showed a remarkable decrease
in Km and a slight alteration in Vmax. The enhancement of soluble starch
catalytic efficiency might be due to the changes of substrate binding ability in
the critical substrate binding sites between the CBM and starch granule.
PMID- 28422447
TI - LC-MS/MS and chiroptical spectroscopic analyses of multidimensional metabolic
systems of chiral thalidomide and its derivatives.
AB - Enantiomeric thalidomide undergoes various kinds of biotransformations including
chiral inversion, hydrolysis, and enzymatic oxidation, which results in several
metabolites, thereby adding to the complexity in the understanding of the nature
of thalidomide. To decipher this complexity, we analyzed the multidimensional
metabolic reaction networks of thalidomide and related molecules in vitro.
Characteristic patterns in the amount of various metabolites of thalidomide and
related molecules generated during a combination of chiral inversion, hydrolysis,
and hydroxylation were observed using liquid chromatography-tandem mass
spectrometry and chiroptical spectroscopy. We found that monosubstituted
thalidomide derivatives exhibited different time-dependent metabolic patterns
compared with thalidomide. We also revealed that monohydrolyzed and
monohydroxylated metabolites of thalidomide were likely to generate mainly by a C
5 oxidation of thalidomide and subsequent ring opening of the hydroxylated
metabolite. Since chirality was conserved in most of these metabolites during
metabolism, they had the same chirality as that of nonmetabolized thalidomide.
Our findings will contribute toward understanding the significant pharmacological
effects of the multiple metabolites of thalidomide and its derivatives.
PMID- 28422448
TI - Benefits of clinical facilitators on improving stroke care in acute hospitals: a
new programme for Australia.
AB - BACKGROUND: Care gaps for stroke lead to preventable disability and deaths. The
Victorian State Government implemented a programme of employing clinical
Facilitators on a fixed-term basis for up to 3 years (2008-2011) in eight
hospitals to improve stroke care. The Facilitators were to establish stroke units
where absent, implement evidence-based management protocols and provide staff
education within an agreed work plan. AIM: To determine if the Facilitator role
was associated with improved stroke care and to describe factors supporting or
mitigating enhancements to care. METHODS: A mixed methods design was employed
with historical control using patient-level audit data (pre-Facilitator: n = 600;
post-Facilitator: n = 387) and qualitative data from independently conducted
semistructured interviews with hospital staff, including clinicians, executives
and facilitators (n = 10 focus groups; 75 respondents). RESULTS: Stroke units,
clinical pathways and outpatient clinics for managing transient ischaemic attacks
(TIA) were established. Compared with the pre-Facilitator period, significant
increases in patient access to stroke unit care (53% vs 86%, P < 0.001) and
intravenous thrombolysis (2% vs 9%, P < 0.001) were achieved. Hospital staff
reported that the Facilitator was integral to system improvements by fostering
communication, encouraging team motivation and cohesiveness and increasing
interest in stroke care. Ongoing barriers included limited resources to operate
TIA clinics effectively, staff turnover requiring ongoing education,
inconsistency in compliance with protocols and, in some hospitals, the need for
formalised medical leadership. CONCLUSION: Fixed-term employment of Facilitators
was effective in positively influencing stroke care in hospitals through a range
of change management strategies where stroke-specific expertise had been
previously limited.
PMID- 28422449
TI - Enhanced chemiluminescence for trazodone trace analysis based on acidic
permanganate oxidation in concurrent presence of rhodamine 6G.
AB - A new sensitized chemiluminescence method by acidic permanganate oxidation was
developed for the sensitive determination of trazodone. A fluorescent dye as used
rhodamine 6G to increase a chemiluminescence intensity. Under optimum conditions,
the liner range of the calibration curve was obtained for 1-5000 nmol/L. The
limit of detection was calculated from 3sigma of a blank was 0.23 nmol/L. The
coexistent ions and substances had no interference with the chemiluminescence
measurement. The chemiluminescence spectra were measured to elucidate a possible
mechanism for the system. The present method was satisfactorily used in the
determination of the drugs in pharmaceutical samples and animal serums.
PMID- 28422450
TI - Erratum to Prenatal diagnosis of focal dermal hypoplasia: Report of three fetuses
and review of the literature.
PMID- 28422451
TI - Multiunit Sequences in First Language Acquisition.
AB - Theoretical and empirical reasons suggest that children build their language not
only out of individual words but also out of multiunit strings. These are the
basis for the development of schemas containing slots. The slots are putative
categories that build in abstraction while the schemas eventually connect to
other schemas in terms of both meaning and form. Evidence comes from the nature
of the input, the ways in which children construct novel utterances, the
systematic errors that children make, and the computational modeling of
children's grammars. However, much of this research is on English, which is
unusual in its rigid word order and impoverished inflectional morphology. We
summarize these results and explore their implications for languages with more
flexible word order and/or much richer inflectional morphology.
PMID- 28422452
TI - Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan
beads.
AB - S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was
produced using immobilized lipase. The lipase enzyme was immobilized on chitosan
beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order
to find an appropriate support for the hydrolysis reaction of racemic naproxen
methyl ester, the conversion and enantioselectivity for all carriers were
compared. In addition, effects of the volumetric ratio of two phases in different
organic solvents, addition of cosolvent and surfactant, optimum pH and
temperature, reusability, and inhibitory effect of methanol were investigated.
The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to
organic phase. Various water miscible and water immiscible solvents were
examined. Finally, isooctane was chosen as an organic solvent, while 2
ethoxyethanol was added as a cosolvent in the organic phase of the reaction
mixture. The optimum reaction conditions were determined to be 35 degrees C, pH
7, and 24 h. Addition of Tween-80 in the organic phase increased the
accessibility of immobilized enzyme to the reactant. The optimum organic phase
compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80
were 3:7 and 0.1% (v/v/v), respectively. The best conversion and
enantioselectivity of immobilized enzyme using chitosan beads activated by
glutaraldehyde were 0.45 and 185, respectively.
PMID- 28422453
TI - How many roads lead to cohesinopathies?
AB - Genetic mapping studies reveal that mutations in cohesion pathways are
responsible for multispectrum developmental abnormalities termed cohesinopathies.
These include Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), and
Warsaw Breakage Syndrome (WABS). The cohesinopathies are characterized by
overlapping phenotypes ranging from craniofacial deformities, limb defects, and
mental retardation. Though these syndromes share a similar suite of phenotypes
and arise due to mutations in a common cohesion pathway, the underlying
mechanisms are currently believed to be distinct. Defects in mitotic failure and
apoptosis i.e. trans DNA tethering events are believed to be the underlying cause
of RBS, whereas the underlying cause of CdLS is largely modeled as occurring
through defects in transcriptional processes i.e. cis DNA tethering events. Here,
we review recent findings described primarily in zebrafish, paired with
additional studies in other model systems, including human patient cells, which
challenge the notion that cohesinopathies represent separate syndromes. We
highlight numerous studies that illustrate the utility of zebrafish to provide
novel insights into the phenotypes, genes affected and the possible mechanisms
underlying cohesinopathies. We propose that transcriptional deregulation is the
predominant mechanism through which cohesinopathies arise. Developmental Dynamics
246:881-888, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28422454
TI - Childhood maltreatment and adulthood poor sleep quality: a longitudinal study.
AB - BACKGROUND: Available evidence from cross-sectional studies suggests that
childhood maltreatment may be associated with a range of sleep disorders.
However, these studies have not controlled for potential individual-, familial-
and environmental-level confounders. AIM: To determine the association between
childhood maltreatment and lower sleep quality after adjusting for potential
confounders. METHODS: Data for the present study were obtained from a pre-birth
cohort study of 3778 young adults (52.6% female) of the Mater Hospital-University
of Queensland Study of Pregnancy follow up at a mean age of 20.6 years. The Mater
Hospital-University of Queensland Study of Pregnancy is a prospective Australian
pre-birth cohort study of mothers consecutively recruited during their first
obstetric clinic visit at Brisbane's Mater Hospital in 1981-1983. Participants
completed the Pittsburgh Sleep Quality Index at the 21-year follow up. We linked
this dataset to agency-recorded substantiated cases of childhood maltreatment. A
series of separate logistic regression models was used to test whether childhood
maltreatment predicted lower sleep quality after adjustment for selected
confounders. RESULTS: Substantiated physical abuse significantly predicted lower
sleep quality in males. Single and multiple forms of childhood maltreatment,
including age of maltreatment and number of substantiations, did not predict
lower sleep quality in either gender in both crude and adjusted models. Not being
married, living in a residential problem area, cigarette smoking and
internalising were significantly associated with lower sleep quality in a fully
adjusted model for the male-female combined sample. CONCLUSIONS: Childhood
maltreatment does not appear to predict young adult poor sleep quality, with the
exception of physical abuse for males. While childhood maltreatment has been
found to predict a range of mental health problems, childhood maltreatment does
not appear to predict sleep problems occurring in young adults. Poor sleep
quality was accounted for by concurrent social disadvantage, cigarette smoking
and internalising.
PMID- 28422455
TI - A decade of leafminer invasion in China: lessons learned.
AB - Liriomyza trifolii (Burgess) is a highly invasive species that has become
established in agricultural and ornamental crops throughout the world. L.
trifolii was first recorded in China in 2005 in Guangdong Province. Subsequently,
its known distribution in China has rapidly expanded to another 11 provinces
(Zhejiang, Jiangsu, Shanghai, Fujian, Guangxi, Shandong, Hainan, Hebei, Henan,
Hubei and Anhui), where it is currently causing considerable damage and economic
losses. Experimental research and field surveys have contributed to our
understanding of the ecology of L. trifolii and particularly the process of
invasion and its interactions with other established, exotic Liriomyza leafminer
species. A number of factors have contributed to the successful establishment of
L. trifolii and displacement of interspecific competitors. In China, L. trifolii
has become a particularly devastating pest in areas with intensive farming with
extensive monocultures and a reliance on insecticide use. Integrated pest
management incorporating judicious applications of insecticide combined with
biological and cultural controls is likely to provide the best long-term
management strategy for L. trifolii. We provide information regarding 10 years of
L. trifolii invasion in China and discuss areas of future research to enhance our
overall understanding of the biology and ecology of L. trifolii and to improve
management programmes for this widespread invasive insect pest. (c) 2017 Society
of Chemical Industry.
PMID- 28422456
TI - Variable phenotype in a novel mutation in PHOX2B.
AB - We evaluated a family with three siblings, two of whom ages 2 years and 19
months, had long segment colonic agangliosis and anisocoria. The mother also had
anisocoria. All three affected family members were mildly dysmorphic with a flat
facial profile, square appearance to the face, depressed nasal bridge, and
anteverted nares. Genetic testing identified a novel heterozygous mutation,
c.234C>G, resulting in a premature stop codon in exon 1 of the PHOX2B gene.
Screening for neural crest tumors was performed in the siblings and to date has
been negative. This family supports a strong association between non polyalanine
tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests
mutation outside of the polyalanine tract may not dictate severe phenotype with
significant respiratory compromise. A unique finding in this family is the
association of congenital heart disease in two of the affected patients. These
malformations may be a sporadic isolated finding or the result of environmental
factors or a modifying allele. Given the association between congenital heart
disease and aberrant neural crest cell development, however, findings are
suggestive that congenital heart disease may be a rare feature of PHOX2B mutation
which has not been previously reported.
PMID- 28422457
TI - Echoes of the Sarajevo Declaration on integrity and visibility of scholarly
publications.
PMID- 28422458
TI - Publication ethics standards should be the same for all peer-reviewed journals.
PMID- 28422459
TI - The Effect of Use of a Sonic Power Toothbrush and a Manual Toothbrush Control on
Plaque and Gingivitis.
AB - OBJECTIVES: To compare the ability of the Philips Sonicare DiamondClean power
toothbrush and the ADA Reference manual toothbrush to reduce plaque and gingival
inflammation by routine manual toothbrush users. METHODS: This was a randomized,
single-blind, parallel-design study. Eligible subjects were generally healthy non
smokers who exhibited mild to moderate gingivitis upon study entry. Enrolled
subjects were randomly allocated to commence twice-daily home use of either a
Philips Sonicare DiamondClean (DiamondClean) power toothbrush or an ADA reference
manual toothbrush (MTB) for a period of four weeks. Clinical safety and efficacy
were assessed after a two- and four-week period of home use. Statistical analysis
was performed for the modified intent to treat (mITT) population using a mixed
model with the Baseline score as a covariate. RESULTS: A total of 182 volunteers
were screened, 144 (72 per treatment) were randomized, and 142 subjects completed
this study. Following four weeks of use, the Least Square (LS) Mean SE) percent
reduction in surface plaque was 34.9% (1.8) for DiamondClean and 8.0% (1.7) for
MTB, (p < 0.0001). At the same four-week time point, the LS Mean (SE) percent
reduction in gingival inflammation for DiamondClean was 25.5% (1.9) and 19.1%
(1.9) for MTB (p = 0.0213). For gingival bleeding, the LS Mean (SE) percent
reduction in sites with gingival bleeding for DiamondClean was 57.4% (3.06) and
31.4% (3.04) for MTB (p < 0.0001). CONCLUSIONS: The Philips Sonicare DiamondClean
power toothbrush was statistically significantly more effective than a manual
toothbrush in reducing supragingival plaque, gingival inflammation, and gingival
bleeding following a four-week period of home use. Both products were safe for
home use.
PMID- 28422460
TI - An Evaluation of Plaque and Gingivitis Reduction Following Home Use of Sonicare
FlexCare Platinum with Premium Plaque Control Brush Head and a Manual Toothbrush.
AB - OBJECTIVES: To assess the effect of the Philips Sonicare FlexCare Platinum with
Premium plaque control brush head on gingival inflammation, bleeding, and
supragingival plaque reduction following a six-week period of home use compared
to a manual toothbrush. METHODS: This was a randomized, single-blind, parallel
design clinical trial. Subjects included in the study were routine manual
toothbrush users who were generally healthy non-smokers, aged 18-65 years, with
mild to moderate gingivitis. Subjects with advanced periodontal disease,
excessive gingival recession, and heavy deposits of calculus or rampant decay
were excluded from the study. Eligible participants were dispensed either Philips
Sonicare FlexCare Platinum with Premium plaque control brush head (PC), or an ADA
Reference manual toothbrush (MTB) for twice-daily home oral hygiene procedures
for six weeks. Efficacy measures included the Lobene and Soparker Modification of
Quigley and Hein Plaque Index (MPI), the Modified Gingival Index (MGI), and
Gingival Bleeding Index (GBI). Safety was evaluated by oral examination and
subject report. Efficacy and safety were assessed at Baseline, and at two and six
weeks following product home use. RESULTS: Of 154 subjects randomized, 143
subjects completed the study. For the primary endpoint, MGI at Week 2,
statistically significantly larger reductions in MGI were observed for PC versus
MTB, p < 0.0001. The adjusted mean reduction and standard error estimates (SE)
for MGI, expressed as percent reduction versus Baseline to Week 2, were 41.73%
(2.00%) for PC and 7.38% (2.02%) for MTB. Statistically significant differences
were also observed for MPI and GBI at Week 2, and for all metrics at Week 6.
CONCLUSIONS: Philips Sonicare FlexCare Platinum with Premium plaque control brush
head statistically significantly reduces gingival inflammation, gingival
bleeding, and plaque following two and six weeks of home use, compared to manual
tooth brushing alone.
PMID- 28422461
TI - The Effectiveness of Manual versus High-Frequency, High-Amplitude Sonic Powered
Toothbrushes for Oral Health: A Meta-Analysis.
AB - OBJECTIVES: Evaluate the short-term clinical efficacy of high-frequency, high
amplitude sonic powered toothbrushes compared to manual toothbrushes on plaque
removal and gingivitis reduction in everyday use through a meta-analysis of
randomized controlled trials. METHODS: Embase, MEDLINE, BIOSIS, Inspec, PQ
SciTech, Compendex, SciSearch and IADR abstracts databases were searched.
Eligible were clinical trials comparing at least one manual to one sonic powered
toothbrush on plaque or gingivitis reduction over four weeks to three months in
subjects without disability that could affect tooth brushing. Two authors
selected and extracted data from eligible studies. When insufficient information
was available, researchers were contacted. Data were pooled using random-effects
models to compute standardized mean differences (SMD) and 95% confidence
intervals (95% CI) quantifying differences in plaque or gingivitis reduction.
Risk for bias and sources of heterogeneity were assessed. RESULTS: The combined
results of 18 studies comprising 1,870 subjects showed that sonic powered
toothbrushes had statistically significantly greater plaque removal (SMD = -0.89,
95%CI = [-1.27, -0.51]) and gingivitis reduction (-0.67, [-1.01, -0.32]).
Heterogeneity was large and bias was not apparent. CONCLUSIONS: High-frequency,
high-amplitude sonic powered toothbrushes decreased plaque and gingivitis
significantly more effectively than manual toothbrushes in everyday use in
studies lasting up to three months.
PMID- 28422462
TI - A Comparison of the Effect of Two Power Toothbrushes on the Gingival Health and
Plaque Status of Subjects with Moderate Gingivitis.
AB - OBJECTIVES: To compare the effect of the Philips Sonicare DiamondClean plus
Premium plaque control brush head with the Oral-B 7000 plus CrossAction brush
head on gingivitis and supragingival plaque reduction following a 42-day period
of home use. METHODS: This was a randomized, parallel, examiner-blind,
prospective clinical trial conducted on generally healthy subjects. Eligible
subjects met the following eligibility criteria: age 18-65, non-smoker, routine
manual toothbrush user, >= 50 sites of gingival bleeding per the Gingival
Bleeding Index (GBI), and >= 1.8 plaque score per the Modified Plaque Index
(MPI), assessed three to six hours following the last oral hygiene procedure.
Eligible subjects were enrolled in the study and randomly assigned to use either
a Philips Sonicare DiamondClean with Premium plaque control brush head power
toothbrush (SPC) or an Oral-B(r) 7000 with CrossActionTM brush head power
toothbrush (OCA), for twice daily home use over a period of 42 days. All subjects
were dispensed a standard fluoride-containing dentifrice and both toothbrushes
were to be used in their respective Deep Clean modes. Safety and efficacy
evaluations were performed at 14 and 42 days following Baseline. RESULTS: Two
hundred eighty-four subjects completed this trial (142 subjects per treatment
group). Least squares mean (95% CI) estimates for reduction and percent reduction
of gingivitis per Modified Gingival Index (MGI) following 42 days of product use
for the SPC group were 1.17 (1.10, 1.24) and 45.68% (42.95%, 48.40%); for the OCA
group they were 0.69 (0.62, 0.76) and 26.83% (24.10%, 29.56%). The mean
difference (95% CI) between the two treatment groups was 0.48 (0.38, 0.58) and
18.85% (14.99%, 22.70%) for reduction and percent reduction, respectively. The
lower limit of the 95% CI for the difference in Overall score between the two
treatment groups was greater than the predefined non-inferiority margin (i.e.,
0.10 or -5%); therefore SPC was declared non-inferior to OCA. In addition, since
the 95% CI for the difference did not include zero, SPC was declared superior to
OCA in the reduction of gingivitis per MGI at Day 42 (p-value < 0.0001).
Similarly, for MGI at Day 14 and for GBI and MPI at Day 14 and Day 42,
significantly larger reductions were observed for SPC compared to OCA (p-value <
0.0001). CONCLUSIONS: Philips Sonicare DiamondClean with Premium plaque control
brush head (SPC) was statistically superior to the Oral-B 7000 with CrossAction
brush head (OCA) in reducing gingival inflammation, gingival bleeding, and
supragingival plaque following 14 and 42 days of home use. Both products were
safe for use.
PMID- 28422463
TI - Gingival Health and Plaque Regrowth Response Following a Four-Week Interdental
Hygiene Intervention.
AB - OBJECTIVES: To compare the efficacy of three adjunct interproximal cleaning
methods versus a manual toothbrush alone on gingivitis, and demonstrate that the
Philips Sonicare AirflossProTM interproximal (IP) cleaning device provides a
similar reduction in gingivitis and plaque compared to string floss. METHODS: A
randomized, single-blind, parallel-design study was conducted on generally
healthy adults exhibiting mild to moderate gingivitis. Eligible subjects were non
smokers, aged 18-65 years, with >= 0.5 per the Rustogi Modified Navy Plaque Index
(RMNPI) and a Gingival Bleeding Index (GBI) of >= 1 on at least 10 sites.
Eligible subjects were randomly assigned to use one of four oral hygiene
regimens: manual toothbrush (MTB) alone; MTB plus string floss (SF); MTB plus
Philips Sonicare AirflossPro used with Cool Mint Listerine(r) Antiseptic (AFPL);
and MTB plus Philips Sonicare AirflossPro used with BreathRxTM (AFPB). Subjects
were followed over a 28-day home-use period, with follow-up visits for efficacy
and safety conducted at Days 14 and 28. All subjects were instructed to use the
MTB twice daily and perform interproximal cleaning once daily, if assigned. Study
efficacy endpoints included the Modified Gingival Index (MGI), Rustogi Modified
Navy Plaque Index, and the Gingival Bleeding Index. RESULTS: Of 290 randomized
subjects, 287 were followed to Day 14 and 286 were followed to Day 28. For the
primary endpoint at Day 14, significantly larger reductions in MGI were observed
in each of the three IP cleaning groups compared to MTB alone (p < 0.001). The
adjusted mean reductions and standard error estimates (SE) for MGI expressed as a
percent reduction from Baseline at Day 14 were: 0.22% (0.55%) for MTB; 4.30%
(0.44%) for SF; 4.55% (0.45%) for AFPL; and 4.20% (0.44%) for AFPB. A non
inferiority test comparing AirflossPro to SF showed AirflossPro to be non
inferior to SF (p < 0.001). CONCLUSIONS: The addition of interproximal cleaning
to manual tooth brushing statistically significantly reduces gingivitis and
plaque compared to manual tooth brushing alone. Among the adjunct interproximal
cleaning regimens, AirflossPro provides a similar reduction in gingivitis and
plaque to string floss. All study regimens were safe on oral tissues.
PMID- 28422470
TI - Corrigendum.
PMID- 28422471
TI - [Epidemiological surveillance for multidrug-resistant microorganisms in a general
ICU].
AB - OBJECTIVE: Multidrug resistant (MDR) microorganisms represent a threat for
patients admitted in Intensive Care Units (ICUs). The objective of the present
study is to analyse the results of epidemiological surveillance cultures for
these microorganisms in one of these units. METHODS: General ICU. Retrospective
analysis, descriptive statistics. Analysis of epidemiological surveillance
cultures for MDR microorganisms in 2015. Studied microorganisms: Methicillin
resistant Staphylococcus aureus (MRSA), ESBL-and/or carbapenemase-producing
Klebsiella pneumoniae (CESBL-KP) and MDR Acinetobacter baumannii (MDRAB).
RESULTS: One thousand, two hundred and fifty nine patients admitted. A total of
2,234 specimens from 384 patients were analysed (690, 634, 62 and 286 were
rectal, throat, nasal and skin swabs respectively). Global APACHE II was 18.3 +/-
8 versus 21.7 +/- 7.8 in patients colonized/infected on admission. Global
mortality was 19.7% versus 22.3% in patients colonized/infected on admission. The
higher sensitivities achieved with the different samples for the different
microorganism detection were as follows. MRSA: 79% and 90% for nasal and nasal +
throat swabs, respectively. MDRAB: 80% and 95% for throat and throat + rectal
swabs, respectively. CESBL-KP: 95% and 98% for rectal and rectal + throat swabs,
respectively. 94 out of the 384 patients (24.4%) were colonized/infected with MDR
at admission. 134 patients (10.6% of the total patients admitted) were
colonized/infected with a total of 169 MMR during the hospital stay. MRSA has the
earliest colonization/infection (9.2 +/- 6.4days) and ESBL-producing
Enterobacteriaceae, the latest (18.7+/- 16.4 days). CONCLUSIONS: 24.4% of
patients were colonized/infected by MDR at admission. Nasal, throat and rectal
swabs were the most effective specimens for recovering MRSA, MDRAB and CESBL-KP,
respectively. The combination of two specimens improves MDR detection except for
CESBL-KP. Skin swabs are worthless. The most prevalent MDR at admission were ESBL
producing Enterobacteriaceae while the most frequent hospital acquired MDR was
MDRAB..
PMID- 28422472
TI - [Post-vaccination varicella in a patient receiving methotrexate].
PMID- 28422473
TI - [Flu in paediatrics: questions and possibilities].
PMID- 28422474
TI - [Comparison of two pattern for Streptococcus agalactiae screening using Granada
media].
PMID- 28422475
TI - [The significance of identification of Streptococcus agalactiae in urine cultures
for detection of Group B streptococcal colonization in pregnant women].
PMID- 28422476
TI - Origin-Dependent Variations in the Atmospheric Microbiome Community in Eastern
Mediterranean Dust Storms.
AB - Microorganisms carried by dust storms are transported through the atmosphere and
may affect human health and the functionality of microbial communities in various
environments. Characterizing the dust-borne microbiome in dust storms of
different origins or that followed different trajectories provides valuable data
to improve our understanding of global health and environmental impacts. We
present a comparative study on the diversity of dust-borne bacterial communities
in dust storms from three distinct origins (North Africa, Syria and Saudi Arabia)
and compare them with local bacterial communities sampled on clear days, all
collected at a single location: Rehovot, Israel. Storms from different dust
origins exhibited distinct bacterial communities, with signature bacterial taxa.
Dust storms were characterized by a lower abundance of selected antibiotic
resistance genes (ARGs) compared with ambient dust, asserting that the origin of
these genes is local and possibly anthropogenic. With the progression of the
storm, the storm-borne bacterial community showed increasing resemblance to
ambient dust, suggesting mixing with local dust. These results show, for the
first time, that dust storms from different sources display distinct bacterial
communities, suggesting possible diverse effects on the environment and public
health.
PMID- 28422477
TI - Core-Shell NiFe-LDH@NiFe-Bi Nanoarray: In Situ Electrochemical Surface Derivation
Preparation toward Efficient Water Oxidation Electrocatalysis in near-Neutral
Media.
AB - The corrosion issue with acidic and alkaline water electrolyzers can be avoided
by developing water oxidation catalysts performing efficiently under benign
conditions. In this Letter, we report that a NiFe-borate layer can be generated
on a NiFe-layered double hydroxide nanosheet array hydrothermally grown on carbon
cloth via an in situ electrochemical surface derivation process in potassium
borate (K-Bi) solution. The resulting 3D NiFe-LDH@NiFe-Bi nanoarray (NiFe
LDH@NiFe-Bi/CC) demonstrates high activity for water oxidation, demanding
overpotentials of 444 and 363 mV to achieve 10 mA cm-2 in 0.1 and 0.5 M K-Bi (pH:
9.2), respectively, rivaling the performances of most reported non-noble-metal
catalysts in near-neutral media. Notably, this electrode also shows strong
electrochemical durability with a high turnover frequency of 0.54 mol O2 s-1 at
overpotential of 600 mV. All these features promise its use as an efficient earth
abundant catalyst material for water oxidation under eco-friendly conditions.
PMID- 28422478
TI - Reduction of Ammineruthenium(III) by Sulfide Enables In Vivo Electrochemical
Monitoring of Free Endogenous Hydrogen Sulfide.
AB - The discovery of endogenous sulfide in mammalian brain opens up a door to
understanding of the physiological function of hydrogen sulfide (H2S). The
transformation of different forms of sulfide (i.e., S2-, HS-, H2S, bound sulfane
sulfur, et al.) in various physiological conditions hurdles the direct detection
of hydrogen sulfide in vivo. Here, we find that ammineruthenium(III) (Ru(NH3)63+)
can catalyze the electrochemical oxidation of free sulfide including HS- and H2S
in a neutral solution (pH 7.4). This property is used to constitute an
electrochemical mechanism for selective detection of hydrogen sulfide. By
coupling in vivo microdialysis with selective electrochemical detection, we
successfully developed an integrated microchip-based online electrochemical
system (OECS) for continuous monitoring of free endogenous hydrogen sulfide in
the central nervous system (CNS). The microchip-based OECS is well responsive
toward hydrogen sulfide with high stability, sensitivity and selectivity.
Compared with the existing methods, the OECS does not require offline treatment
of brain tissue or adjustment of the detection solutions into acidic or strong
basic atmosphere. These priorities essentially enable the system to accurately
and reliably track dynamics of hydrogen sulfide in the CNS.
PMID- 28422479
TI - On-Demand Gas-to-Liquid Process To Fabricate Thermoresponsive Antimicrobial
Nanocomposites and Coatings.
AB - Antimicrobial material is emerging as a major component of the mitigation
strategy against microbial growth on abiotic surfaces. In this work, a newly
designed process is proposed to fabricate thermoresponsive antimicrobial
nanocomposites (TANs) and coatings (TACs) as an on-demand system.
Thermoresponsive polymer (TRP)-incorporated silver (Ag) nanocomposites with
silica nanoparticles (SNPs) or carbon nanotubes (CNTs; Ag-SNP@TRP or Ag-CNT@TRP)
were produced by a single-pass gas-to-liquid process. The SNPs or CNTs were first
produced by spark ablation and successively injected for dispersal in a liquid
cell containing polydimethylsiloxane, poly(N-isopropylacrylamide), and silver
nitrate under ultrasound irradiation. Suspensions of Ag-SNP@TRP or Ag-CNT@TRP
nanocomposites were then deposited on a touch screen panel (TSP) protection film
via electrohydrodynamic spray to form transparent antibacterial coatings.
Fundamental antibacterial activities of TANs were evaluated against Escherichia
coli and Staphylococcus epidermidis. The TANs showed stronger antibacterial
activities at the higher temperature for all testing conditions. Lower minimum
inhibitory concentrations of Ag-SNP@TRP and Ag-CNT@TRP nanocomposites were
required against the two bacteria at 37 degrees C compared to those at 27
degrees C. The TACs on display showed elevated antimicrobial activity when the
panel was turned on (38.1 degrees C) compared with when the panel was turned off
(23.8 degrees C). This work provides a utilizable concept to continuously
fabricate TANs and TACs, and it specifically offers stimuli-sensitive control of
antimicrobial activity on TSPs, including other frequently touched surfaces.
PMID- 28422480
TI - Chemical Characterization of Gas- and Particle-Phase Products from the Ozonolysis
of alpha-Pinene in the Presence of Dimethylamine.
AB - Amines are recognized as key compounds in new particle formation (NPF) and
secondary organic aerosol (SOA) formation. In addition, ozonolysis of alpha
pinene contributes substantially to the formation of biogenic SOAs in the
atmosphere. In the present study, ozonolysis of alpha-pinene in the presence of
dimethylamine (DMA) was investigated in a flow tube reactor. Effects of amines on
SOA formation and chemical composition were examined. Enhancement of NPF and SOA
formation was observed in the presence of DMA. Chemical characterization of gas-
and particle-phase products by high-resolution mass spectrometric techniques
revealed the formation of nitrogen containing compounds. Reactions between
ozonolysis reaction products of alpha-pinene, such as pinonaldehyde or pinonic
acid, and DMA were observed. Possible reaction pathways are suggested for the
formation of the reaction products. Some of the compounds identified in the
laboratory study were also observed in aerosol samples (PM1) collected at the
SMEAR II station (Hyytiala, Finland) suggesting that DMA might affect the
ozonolysis of alpha-pinene in ambient conditions.
PMID- 28422481
TI - Gold Nanoparticles Induced Endothelial Leakiness Depends on Particle Size and
Endothelial Cell Origin.
AB - The endothelium presents a formidable barrier for cancer nanomedicine, as the
intravenously introduced nanomedicine needs to leave the blood vessel at the
tumor site. Endothelial permeability and retention effect (EPR) is not dependable
since it is derived from tumors. Certain nanoparticles with specific
characteristics are able to induce micrometer sized gaps between endothelial
cells. This effect is called "nanoparticle induced endothelial leakiness"
(NanoEL). NanoEL therefore allows the nanotechnology to control access to the
tumor even in the absence of any EPR effect. Morever, NanoEL can be applicable to
noncancer issues, thereby expanding its usefulness in other subfields of
nanomedicine. In this paper, we have shown that Gold (Au) nanoparticles within
the range of 10-30 nm are good NanoEL inducing particles. As not all endothelial
cells have the same permeability, we found that human mammary endothelial cells
and human skin endothelial cells are sensitive to Au induced NanoEL, while human
umbilical vein endothelial cells are insensitive, reflective of their innate
nature of endothelial permeability. The size window and endothelial cell type
sensitivity then helps the nanotechnologists to design future nanoparticles that
either exploit NanoEL as a nanotechnology driven strategy to access immature
tumors, which do not induce the EPR effect, or avoid NanoEL as a nanotoxic side
effect.
PMID- 28422482
TI - Organosilica Nanoparticles with an Intrinsic Secondary Amine: An Efficient and
Reusable Adsorbent for Dyes.
AB - Nanomaterials are promising tools in water remediation because of their large
surface area and unique properties compared to bulky materials. We synthesized an
organosilica nanoparticle (OSNP) and tuned its composition for anionic dye
removal. The adsorption mechanisms are electrostatic attraction and hydrogen
bonding between the amine on OSNP and the dye, and the surface charge of the OSNP
can be tuned to adsorb either anionic or cationic dyes. Using phenol red as a
model dye, we studied the effect of the amine group, pH, ionic strength, time,
dye concentration, and nanomaterial mass on the adsorption. The theoretical
maximum adsorption capacity was calculated to be 175.44 mg/g (0.47 mmol/g), which
is higher than 67 out of 77 reported adsorbents. The experimental maximum
adsorption capacity is around 201 mg/g (0.53 mmol/g). Furthermore, the
nanoparticles are highly reusable and show stable dye removal and recovery
efficiency over at least 10 cycles. In summary, the novel adsorbent system
derived from the intrinsic amine group within the frame of OSNP are reusable and
tunable for anionic or cationic dyes with high adsorption capacity and fast
adsorption. These materials may also have utility in drug delivery or as a
carrier for imaging agents.
PMID- 28422483
TI - Transparent Flexible Multifunctional Nanostructured Architectures for Non-optical
Readout, Proximity, and Pressure Sensing.
AB - Electronic skins need to be versatile and able to detect multiple inputs beyond
simple pressure and touch while having attributes of transparency and facile
manufacturability. Herein, we demonstrate a versatile nanostructured transparent
sensor capable of detecting wide range of pressures and proximity as well as
novel nonoptical detection of printed patterns. The architecture and fabrication
processes are straightforward and show robustness to repeated cycling and
testing. The sensor displays good sensitivity and stability from 30 Pa to 5 kPa
without the use of microstructuration and is conformal and sensitive to be
utilized as a wrist-based heart-rate monitor. Highly sensitive proximity
detection is shown from a distance of 9 cm. Finally, a unique nonoptical pattern
recognition dependent on the difference in the dielectric constant between ink
and paper is also demonstrated, indicating the multifunctionality of this simple
architecture.
PMID- 28422484
TI - Direct Synthesis of Dextran-Based Antibacterial Hydrogels for Extended Release of
Biocides and Eradication of Topical Biofilms.
AB - Cationic small molecular biocides have been developed as promising antibiofilm
agents because of their tunability in chemical structures and their ability to
disrupt established biofilms. However, the impact of biocides in antibiofilm
treatment is largely limited due to the lack of an effective delivery system that
can ensure sustained release of biocides at the target site. Herein we report a
biocide-encapsulated antibacterial and antibiofilm hydrogel that acts as an
efficient delivery vehicle for the biocide and eradicates matured bacterial
biofilm. The hydrogels are prepared using dextran methacrylate (Dex-MA), a
biocompatible and photopolymerizable polymer, and a nontoxic cationic biocide
with two cationic charges, two nonpeptidic amide bonds, and optimized
amphiphilicity, which is capable of eradicating established bacterial biofilms.
The gels, prepared via direct loading of the biocide and with highly controllable
amounts, display 100% activity against both drug-sensitive and drug-resistant
bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Importantly,
the gels are shown to release the biocide and kill bacteria for an extended
period of time (until day 5). When being treated with the established bacterial
biofilms, the released biocide from the gel is shown to completely eradicate
establishedS. aureus, Escherichia coli, and MRSA biofilms, the most common
biofilm forming bacteria that cause severe infections (e.g., skin infections,
urinary tract infections, etc.) in humans. Moreover, the gels were shown to
annihilate preformed MRSA biofilm with >99.99% bacterial reduction under in vitro
and in vivo conditions in a superficial MRSA infection model in mice. Notably,
when tested, excellent skin compatibility is observed for these materials in
various animal models such as a rat model of acute dermal toxicity, guinea pig
model of skin sensitization, and rabbit model of skin irritation. The
biocompatible antibacterial and antibiofilm hydrogels developed herein thus might
be useful in treating bacterial biofilm associated infections, especially topical
infections.
PMID- 28422485
TI - Fabrication of a Highly Sensitive Single Aligned TiO2 and Gold Nanoparticle
Embedded TiO2 Nano-Fiber Gas Sensor.
AB - In this research, a single-aligned nanofiber of pure TiO2 and gold nanoparticle
(GNP)-TiO2 were fabricated using a novel electro-spinning procedure equipped with
secondary electrostatic fields on highly sharp triangular and rectangular
electrodes provided for gas sensing applications. The sol used for spinning
nanofiber consisted of titanium tetraisopropoxide (C12H28O4Ti), acetic acid
(CH3COOH), ethanol (C2H5OH), polyvinylpyrrolidone (PVP), and gold nanoparticle
solution. FE-SEM, TEM, and XRD were used to characterize the single nanofiber. In
triangular electrodes, the electrostatic voltage for aligning single nanofiber
between electrodes depends on the angle tip of the electrode, which was around
1.4-2.1, 2-2.9, and 3.2-4.1 kV for 30 degrees , 45 degrees , and 60 degrees ,
respectively. However, by changing the shape of the electrodes to rectangular
samples and by increasing distance between electrodes from 100 to 200 MUm,
electro-spinning applied voltage decreased. Response of pure TiO2 single
nanofiber sensor was measured for 30-200 ppb carbon monoxide gas. The triangular
sample revealed better response and lower threshold than the rectangular sample.
Adding appropriate amounts of GNP decreased the operating temperature and
increased the responses. CO concentration threshold for the pure TiO2 and GNP
TiO2 triangular samples was about 5 ppb and 700 ppt, respectively.
PMID- 28422486
TI - Stable Nanocomposite Based on PEGylated and Silver Nanoparticles Loaded Graphene
Oxide for Long-Term Antibacterial Activity.
AB - The increasing occurrence of antibiotic-resistant pathogens, especially
superbugs, is compromising the efficacy of traditional antibiotics. Silver
nanoparticles (AgNPs) loaded graphene oxide (GO) nanocomposite (GO-Ag) has drawn
great interest as a promising alternative antibacterial material. However, GO-Ag
nanocomposite often irreversibly aggregates in physiological solutions, severely
influencing its antibacterial capacity and practical application. Herein, a
PEGylated and AgNPs loaded GO nanocomposite (GO-PEG-Ag) is synthesized through a
facile approach utilizing microwave irradiation, while avoiding extra reducing
agents. Through PEGylation, the synthesized GO-PEG-Ag nanocomposite dispersed
stably over one month in a series of media and resisted centrifugation at 10
000*g for 5 min, which would benefit effective contact between the nanocomposite
and the bacteria. In contrast, GO-Ag aggregated within 1 h of dispersion in
physiological solutions. In comparison with GO-Ag, GO-PEG-Ag showed stronger
bactericidal capability toward not only normal Gram-negative/positive bacteria
such as E. coli and S. aureus (~100% of E. coli and ~95.3% of S. aureus reduction
by 10 MUg/mL nanocomposite for 2.5 h), but also superbugs. Moreover, GO-PEG-Ag
showed lower cytotoxicity toward HeLa cells. Importantly, GO-PEG-Ag presented
long-term antibacterial effectiveness, remaining ~95% antibacterial activity
after one-week storage in saline solution versus <35% for GO-Ag. The
antibacterial mechanisms of GO-PEG-Ag were evidenced as damage to the bacterial
structure and production of reactive oxygen species, causing cytoplasm leakage
and metabolism decrease. The stable GO-PEG-Ag nanocomposite with powerful and
long-term antibacterial capability provides a more practical and effective
strategy for fighting superbugs-including pathogen threats in biomedicine and
public health.
PMID- 28422487
TI - Stepwise Deoxygenation of Nitrite as a Route to Two Families of Ruthenium
Corroles: Group 8 Periodic Trends and Relativistic Effects.
AB - Given the many applications of ruthenium porphyrins, the rarity of ruthenium
corroles and the underdeveloped state of their chemistry are clearly indicative
of an area ripe for significant breakthroughs. The tendency of ruthenium corroles
to form unreactive metal-metal-bonded dimers has been recognized as a key
impediment in this area. Herein, by exposing free-base meso-tris(p-X
phenyl)corroles, H3[TpXPC] (X = CF3, H, Me, and OMe), and [Ru(COD)Cl2]x in
refluxing 2-methoxyethanol to nitrite, we have been able to reliably intercept
the series Ru[TpXPC](NO) in a matter of seconds to minutes and subsequently
RuVI[TpXPC](N), the products of a second deoxygenation, over some 16 h. Two of
the RuVIN complexes and one ruthenium corrole dimer could be crystallographically
analyzed; the Ru-Nnitrido distance was found to be ~1.61 A, consistent with the
triple-bonded character of the RuVIN units and essentially identical with the Os
Nnitrido distance in analogous osmium corroles. Spectroscopic and density
functional theory (DFT) calculations suggest that the RuNO corroles are best
viewed as innocent {RuNO}6 complexes, whereas the analogous FeNO corroles are
noninnocent, i.e., best viewed as {FeNO}7-corrole*2-. Both RuVIN and OsVIN
corroles exhibit sharp Soret bands, suggestive of an innocent macrocycle. A key
difference between the two metals is that the Soret maxima of the OsVIN corroles
are red-shifted some 25 nm relative to those of the RuVIN complexes. Careful time
dependent DFT studies indicate that this difference is largely attributable to
relativistic effects in OsVIN corroles. The availability of two new classes of
mononuclear ruthenium corroles potentially opens the door to new applications, in
such areas as catalysis and cancer therapy.
PMID- 28422488
TI - Pressure-Driven Isostructural Phase Transition in InNbO4: In Situ Experimental
and Theoretical Investigations.
AB - The high-pressure behavior of technologically important visible-light
photocatalytic semiconductor InNbO4, adopting a monoclinic wolframite-type
structure at ambient conditions, was investigated using synchrotron-based X-ray
diffraction, Raman spectroscopic measurements, and first-principles calculations.
The experimental results indicate the occurrence of a pressure-induced
isostructural phase transition in the studied compound beyond 10.8 GPa. The large
volume collapse associated with the phase transition and the coexistence of two
phases observed over a wide range of pressure shows the nature of transition to
be first-order. There is an increase in the oxygen anion coordination number
around In and Nb cations from six to eight at the phase transition. The ambient
pressure phase has been recovered on pressure release. The experimental pressure
volume data when fitted to a Birch-Murnaghan equation of states yields the value
of ambient pressure bulk modulus as 179(2) and 231(4) GPa for the low- and high
pressure phases, respectively. The pressure dependence of the Raman mode
frequencies and Gruneisen parameters was determined for both phases by
experimental and theoretical methods. The same information is obtained for the
infrared modes from first-principles calculations. Results from theoretical
calculations corroborate the experimental findings. They also provide information
on the compressibility of interatomic bonds, which is correlated with the
macroscopic properties of InNbO4.
PMID- 28422489
TI - Generalized Switch Functions in the Multilevel Many-Body Expansion Method and Its
Application to Water Clusters.
AB - The many-body expansion (MBE) method is the basis of many fragment-based methods
and is widely applied to the computation of large molecular systems. To reach
linear-scaling computation, a cutoff must be used to discard those subsystems
with long interfragment distances. However, this leads to a discontinuous
potential energy surface (PES) that would cause various problems in geometry
optimizations and molecular dynamics simulations. To solve this problem, we
present a generalized-switch-function (GSF) approach to smooth the PES computed
by the MBE method with the use of a cutoff distance. The GSFs are naturally
normalized and are permutation invariant. This approach can be applied to
adaptively computing any order of many-body correction energies with multilevel
computational methods and is a dynamic subsystem approach. We have applied the
two versions of our method, GSF-MBE(m)/L1 and GSF-MBE(m)/(L1:L2:L3), to water
clusters. Thorough tests show that our method can indeed give smooth potential
energy surface and is linear scaling but without losing much accuracy for very
large water clusters with appropriately chosen cutoff distances.
PMID- 28422490
TI - Redox-Tagged Carbon Monoxide-Releasing Molecules (CORMs): Ferrocene-Containing
[Mn(C^N)(CO)4] Complexes as a Promising New CORM Class.
AB - This study describes the synthesis and characterization of a new class of
ferrocene-containing carbon monoxide-releasing molecules (CORMs, 1-3). The
ferrocenyl group is both a recognized therapeutically viable coligand and a
handle for informative infrared spectroelectrochemistry. Deoxymyoglobin CO
release assays and in situ infrared spectroscopy confirm compounds 2 and 3 as
photoCORMs and 1 as a thermal CORM, attributed to the increased sensitivity of
the Mn-ferrocenyl bond to protonation in 1. Electrochemical and infrared
spectroelectrochemical experiments confirm a single reversible redox couple
associated with the ferrocenyl moiety with the Mn tetracarbonyl center showing no
redox activity up to +590 mV vs Fc/Fc+, though no concomitant CO release was
observed in association with the redox activity. The effects of linker length on
communication between the Fe and Mn centers suggest that the incorporation of
redox-active ligands into CORMs focuses on the first coordination sphere of the
CORM. Redox-tagged CORMs could prove to be a useful mechanistic probe; our
findings could be developed to use redox changes to trigger CO release.
PMID- 28422491
TI - Discovery of Novel Ligands for TNF-alpha and TNF Receptor-1 through Structure
Based Virtual Screening and Biological Assay.
AB - Tumor necrosis factor alpha (TNF-alpha) is overexpressed in various diseases, and
it has been a validated therapeutic target for autoimmune diseases. All
therapeutics currently used to target TNF-alpha are biomacromolecules, and
limited numbers of TNF-alpha chemical inhibitors have been reported, which makes
the identification of small-molecule alternatives an urgent need. Recent studies
have mainly focused on identifying small molecules that directly bind to TNF
alpha or TNF receptor-1 (TNFR1), inhibit the interaction between TNF-alpha and
TNFR1, and/or regulate related signaling pathways. In this study, we combined in
silico methods with biophysical and cell-based assays to identify novel
antagonists that bind to TNF-alpha or TNFR1. Pharmacophore model filtering and
molecular docking were applied to identify potential TNF-alpha antagonists. In
regard to TNFR1, we constructed a three-dimensional model of the TNF-alpha-TNFR1
complex and carried out molecular dynamics simulations to sample the
conformations. The residues in TNF-alpha that have been reported to play
important roles in the TNF-alpha-TNFR1 complex were removed to form a pocket for
further virtual screening of TNFR1-binding ligands. We obtained 20 virtual hits
and tested them using surface plasmon resonance-based assays, which resulted in
one ligand that binds to TNFR1 and four ligands with different scaffolds that
bind to TNF-alpha. T1 and R1, the two most active compounds with Kd values of 11
and 16 MUM for TNF-alpha and TNFR1, respectively, showed activities similar to
those of known antagonists. Further cell-based assays also demonstrated that T1
and R1 have similar activities compared to the known TNF-alpha antagonist C87.
Our work has not only produced several TNF-alpha and TNFR1 antagonists with novel
scaffolds for further structural optimization but also showcases the power of our
in silico methods for TNF-alpha- and TNFR1-based drug discovery.
PMID- 28422492
TI - A Concise, Efficient and Scalable Total Synthesis of Thapsigargin and
Nortrilobolide from (R)-(-)-Carvone.
AB - A concise, efficient and scalable synthesis of thapsigargin and nortrilobolide
from commercially available (R)-(-)-carvone was developed. Our synthetic strategy
is inspired by nature's carbon-carbon bond formation sequence, which facilitates
the construction of a highly functionalized sesquiterpene lactone skeleton in
five steps via an enantioselective ketone alkylation and a diastereoselective
pinacol cyclization. We envision that this strategy will permit the construction
of other members of the family, structural analogs and provide a practical
synthetic route to these important bioactive agents. In addition, we anticipate
that the prodrug Mipsagargin, which is currently in late-stage clinical trials
for the treatment of cancer, will also be accessible via this strategy. Hence,
the limited availability from natural sources, coupled with an estimated demand
of one metric ton per annum for the prodrug, provides a compelling mandate to
develop practical total syntheses of these agents.
PMID- 28422493
TI - Triazolide Strigolactone Mimics Influence Root Development in Arabidopsis.
AB - Strigolactones are the most recently recognized class of phytohormones, which are
also known to establish plant symbiosis with arbuscular mycorhizal fungi or
induce germination of parasitic plants. Their relatively complex structures and
low stability urgently calls for simple derivatives with maintained biological
function. We have prepared a series of triazolide strigolactone mimics and
studied their ability to affect root development of Arabidopsis thaliana. The
strigolactone mimics significantly induced root elongation and lateral root
formation while resembling the effect of the reference compound GR24.
PMID- 28422494
TI - Genetically Encoded 2-Aryl-5-carboxytetrazoles for Site-Selective Protein Photo
Cross-Linking.
AB - The genetically encoded photo-cross-linkers promise to offer a temporally
controlled tool to map transient and dynamic protein-protein interaction
complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5
carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation
into proteins via amber codon suppression in Escherichia coli and mammalian
cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was
found to give robust and site-selective photo-cross-linking reactivity in E. coli
when placed at an appropriate site at the protein interaction interface. A
comparison study indicated that mPyTK exhibits higher photo-cross-linking
efficiency than a diazirine-based photo-cross-linker, AbK, when placed at the
same location of the interaction interface in vitro. When mPyTK was introduced
into the adapter protein Grb2, it enabled the photocapture of EGFR in a stimulus
dependent manner. The design of mPyTK along with the identification of its
cognate aminoacyl-tRNA synthetase makes it possible to map transient protein
protein interactions and their interfaces in living cells.
PMID- 28422495
TI - Cochliotoxin, a Dihydropyranopyran-4,5-dione, and Its Analogues Produced by
Cochliobolus australiensis Display Phytotoxic Activity against Buffelgrass
(Cenchrus ciliaris).
AB - Buffelgrass (Pennisetum ciliare or Cenchrus ciliaris) is a perennial grass that
has become highly invasive in the Sonoran Desert of southern Arizona. In the
search for novel control strategies against this weed, strains of the foliar
fungal pathogen Cochliobolus australiensis from buffelgrass have been screened
for their ability to produce phytotoxic metabolites that could potentially be
used as natural herbicides in an integrated pest management strategy. A new
phytotoxin, named cochliotoxin, was isolated from liquid culture of this fungus
together with radicinin, radicinol, and their 3-epimers. Cochliotoxin was
characterized, essentially by spectroscopic methods, as 3-hydroxy-2-methyl-7-(3
methyloxiranyl)-2,3-dihydropyrano[4,3-b]pyran-4,5-dione. Its relative
stereochemistry was assigned by 1H NMR techniques, while the absolute
configuration (2S,3S) was determined applying the advanced Mosher's method by
esterification of its hydroxy group at C-3. When bioassayed in a buffelgrass
coleoptile elongation test and by leaf puncture bioassay against the host weed
and two nontarget grasses, cochliotoxin showed strong phytotoxicity. In the same
tests, radicinin and 3-epi-radicinin also showed phytotoxic activity, while
radicinol and 3-epi-radicinol were largely inactive. All five compounds were more
active in leaf puncture bioassays on buffelgrass than on the nontarget grass
tanglehead (Heteropogon contortus), while the nontarget grass Arizona cottontop
(Digitaria californica) was more sensitive to radicinin and 3-epi-radicinin.
Cochliotoxin at low concentration was significantly more active on buffelgrass
than on either native grass, but the difference was small.
PMID- 28422496
TI - The Combined Use of Proteomics and Transcriptomics Reveals a Complex Secondary
Metabolite Network in Peperomia obtusifolia.
AB - Peperomia obtusifolia, an ornamental plant from the Piperaceae family,
accumulates a series of secondary metabolites with interesting biological
properties. From a biosynthesis standpoint, this species produces several
benzopyrans derived from orsellinic acid, which is a polyketide typically found
in fungi. Additionally, the chiral benzopyrans were reported as racemic and/or as
diastereomeric mixtures, which raises questions about the level of enzymatic
control in the cyclization step for the formation of the 3,4-dihydro-2H-pyran
moiety. Therefore, this article describes the use of shotgun proteomic and
transcriptome studies as well as phytochemical profiling for the characterization
of the main biosynthesis pathways active in P. obtusifolia. This combined
approach resulted in the identification of a series of proteins involved in its
secondary metabolism, including tocopherol cyclase and prenyltransferases. The
activity of these enzymes was supported by the phytochemical profiling performed
in different organs of P. obtusifolia. However, the polyketide synthases possibly
involved in the production of orsellinic acid could not be identified, suggesting
that orsellinic acid may be produced by endophytes intimately associated with the
plant.
PMID- 28422497
TI - Mechanistic Study of Arylsilane Oxidation through 19F NMR Spectroscopy.
AB - The mechanism of the oxidation of arylsilanes to phenols has been investigated
using 19F NMR spectroscopy. The formation of silanols in these reactions results
from a rapid background equilibrium between silanol and alkoxysilane; the
relative rates of reaction of these species was evaluated by modeling of
concentration profiles obtained through 19F NMR spectroscopic reaction
monitoring. Combining these results with a study of initial rates of phenol
formation, and of substituent electronic effects, a mechanistic picture involving
rapid and reversible formation of a pentavalent peroxide ate complex, prior to
rate-limiting aryl migration, has evolved.
PMID- 28422498
TI - Selective Oxygenation of Cyclohexene by Dioxygen via an Iron(V)-Oxo Complex
Autocatalyzed Reaction.
AB - An iron complex with a tetraamido macrocyclic ligand, [(TAML)FeIII]-, was found
to be an efficient and selective catalyst for allylic oxidation of cyclohexene by
dioxygen (O2); cyclohex-2-enone was obtained as the major product along with
cyclohexene oxide as the minor product. An iron(V)-oxo complex, [(TAML)FeV(O)]-,
which was formed by activating O2 in the presence of cyclohexene, initiated the
autoxidation of cyclohexene with O2 to produce cyclohexenyl hydroperoxide, which
reacted with [(TAML)FeIII]- to produce [(TAML)FeV(O)]- by autocatalysis. Then,
[(TAML)FeV(O)]- reacted rapidly with [(TAML)FeIII]- to produce a MU-oxo dimer,
[(TAML)FeIV(O)FeIV(TAML)]2-, which was ultimately converted to [(TAML)FeV(O)]-
when [(TAML)FeIII]- was not present in the reaction solution. An induction period
was observed in the autocatalytic production of [(TAML)FeV(O)]-. The induction
period was shortened with increasing catalytic amounts of [(TAML)FeV(O)]- and
cyclohexenyl hydroperoxide, whereas the induction period was prolonged by adding
catalytic amounts of a spin trapping reagent such as 5,5-dimethyl-1-pyrroline N
oxide (DMPO). The allylic oxidation of cycloalkenes was also found to depend on
the allylic C-H bond dissociation energies, suggesting that the hydrogen atom
abstraction from the allylic C-H bonds of cycloalkenes is the rate-determining
radical chain initiation step. In this study, we have shown that an iron(III)
complex with a tetraamido macrocyclic ligand is an efficient catalyst for the
allylic oxidation of cyclohexene via an autocatalytic radical chain mechanism and
that [(TAML)FeV(O)]- acts as a reactive intermediate for the selective
oxygenation of cyclohexene with O2 to produce cyclohex-2-enone predominantly.
PMID- 28422499
TI - Development of a 18F-Labeled Radiotracer with Improved Brain Kinetics for
Positron Emission Tomography Imaging of Translocator Protein (18 kDa) in Ischemic
Brain and Glioma.
AB - We designed four novel acetamidobenzoxazolone compounds 7a-d as candidates for
positron emission tomography (PET) radiotracers for imaging the translocator
protein (18 kDa, TSPO) in ischemic brain and glioma. Among these compounds, 2-(5
(6-fluoropyridin-3-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide
(7d) exhibited high binding affinity (Ki = 13.4 nM) with the TSPO and moderate
lipophilicity (log D = 1.92). [18F]7d was radiosynthesized by [18F]fluorination
of the bromopyridine precursor 7h with [18F]F- in 12 +/- 5% radiochemical yield
(n = 6, decay-corrected). In vitro autoradiography and PET studies of ischemic
rat brain revealed higher binding of [18F]7d with TSPO on the ipsilateral side,
as compared to the contralateral side, and improved brain kinetics compared with
our previously developed radiotracers. Metabolite study of [18F]7d showed 93% of
unchanged form in the ischemic brain at 30 min after injection. Moreover, PET
study with [18F]7d provided a clear tumor image in a glioma-bearing rat model. We
demonstrated that [18F]7d is a useful PET radiotracer for visualizing not only
neuroinflammation but also glioma and will translate this radiotracer to a "first
in-human" study in our facility.
PMID- 28422500
TI - Influence of 13C Isotopic Labeling Location on Dynamic Nuclear Polarization of
Acetate.
AB - Dynamic nuclear polarization (DNP) via the dissolution method has alleviated the
insensitivity problem in liquid-state nuclear magnetic resonance (NMR)
spectroscopy by amplifying the signals by several thousand-fold. This NMR signal
amplification process emanates from the microwave-mediated transfer of high
electron spin alignment to the nuclear spins at high magnetic field and cryogenic
temperature. Since the interplay between the electrons and nuclei is crucial, the
chemical composition of a DNP sample such as the type of free radical used,
glassing solvents, or the nature of the target nuclei can significantly affect
the NMR signal enhancement levels that can be attained with DNP. Herein, we have
investigated the influence of 13C isotopic labeling location on the DNP of a
model 13C compound, sodium acetate, at 3.35 T and 1.4 K using the narrow electron
spin resonance (ESR) line width free radical trityl OX063. Our results show that
the carboxyl 13C spins yielded about twice the polarization produced in methyl
13C spins. Deuteration of the methyl 13C group, while proven beneficial in the
liquid-state, did not produce an improvement in the 13C polarization level at
cryogenic conditions. In fact, a slight reduction of the solid-state 13C
polarization was observed when 2H spins are present in the methyl group.
Furthermore, our data reveal that there is a close correlation between the solid
state 13C T1 relaxation times of these samples and the relative 13C polarization
levels. The overall results suggest the achievable solid-state polarization of
13C acetate is directly affected by the location of the 13C isotopic labeling via
the possible interplay of nuclear relaxation leakage factor and cross-talks
between nuclear Zeeman reservoirs in DNP.
PMID- 28422501
TI - Interfacial Activity of Nonamphiphilic Particles in Fluid-Fluid Interfaces.
AB - Surfactants can adsorb in fluid-fluid interfaces and lower the interfacial
tension. Like surfactants, particles with appropriate wettability can also adsorb
in fluid-fluid interfaces. Despite many studies of particle adsorption at fluid
interfaces, some confusion persists regarding the ability of (simple,
nonamphiphilic) particles to reduce the interfacial tension. In the present work,
the interfacial activity of silica nanoparticles at air-water and hexadecane
water interfaces and of ethyl cellulose particles at the interface of water with
trimethylolpropane trimethacrylate was analyzed through pendant drop tensiometry.
Our measurements strongly suggest that the particles do significantly affect the
interfacial tension provided that they have a strong affinity to the interface by
virtue of their wettability and that no energy barrier to adsorption prevents
them from reaching the interface. A simplistic model that does not explicitly
account for any particle-particle interactions is found to yield surprisingly
good predictions for the effective interfacial tension in the presence of the
adsorbed particles. We further propose that interfacial tension measurements,
when combined with information about the particles' wetting properties, can
provide a convenient way to estimate the packing density of particles in fluid
fluid interfaces. These results may help to understand and control the assembly
of nonamphiphilic nanoparticles at fluid-fluid interfaces, which is relevant to
applications ranging from surfactant-free formulations and food technology to oil
recovery.
PMID- 28422502
TI - Arrays of Ag and Au Nanoparticles with Terpyridine- and Thiophene-Based Ligands:
Morphology and Optical Responses.
AB - The assembly of Ag and Au nanoparticles (NPs) into nanoparticulate arrays
mediated by terpyridine (tpy), 4'-(2-thienyl)terpyridine (T-tpy), and short
alpha,omega-bis(tpy)oligothiophene ligands has been accomplished at the interface
between the Ag or Au NP hydrosol and a solution of the molecular species in
dichloromethane. The relationship between the morphology and the optical
responses of the arrays has been investigated by advanced methods of TEM
(transmission electron microscopy) image analysis and surface plasmon extinction
(SPE) spectra. It has been established that the size of islands of closely spaced
NPs rather than the average interparticle distance affects the extent of
delocalization of the surface plasmon excitations and thus also the SPE spectra.
Furthermore, the structure of surface-adsorbate complexes formed in these arrays
has been investigated by SERS spectral measurements carried out as a function of
the excitation wavelength. Photoinduced charge transfer (CT) transitions from the
neutral Ags0 and Aus0 adsorption sites on metal NPs to antibonding orbitals of
the adsorbates have been identified for Ag/tpy, Ag/T-tpy, Au/tpy, and Au/T-tpy
nanoparticulate arrays. Although the surface-adsorbate complexes displaying a
photoinduced CT are known for Ag NPs, the Aus0 surface complexes with this CT are
newly reported. Bis(tpy)oligothiophenes were found to be attached to both Ag and
Au NPs via the tpy group(s). The match between the interparticle distances within
the NP islands and the lengths of the oligomers molecules indicates that the
molecules act as interparticle linkers. In this case, unequivocal spectral marker
band evidence of the Ags0 as well as Aus0 surface complex formation has not been
obtained.
PMID- 28422503
TI - Predicting Protein Interactions of Concentrated Globular Protein Solutions Using
Colloidal Models.
AB - Protein interactions of alpha-chymotrypsinogen A (aCgn) were quantified using
light scattering from low to high protein concentrations. Static light scattering
(SLS) was used to determine the excess Rayleigh ratio (Rex) and osmotic second
virial coefficients (B22) as a function of pH and total ionic strength (TIS).
Repulsive (attractive) protein-protein interactions (PPI) were observed at pH 5
(pH 7), with decreasing repulsions (attractions) upon increasing TIS. Simple
colloidal potential of mean force models (PMF) that account for short-range
nonelectrostatic attractions and screened electrostatic interactions were used to
fit model parameters from data for B22 vs TIS at both pH values. The parameters
and PMF models from low-concentration conditions were used as the sole input to
transition matrix Monte Carlo simulations to predict high concentration Rex
behavior. At conditions where PPI are repulsive to slightly attractive,
experimental Rex data at high concentrations could be predicted quantitatively by
the simulations. However, accurate predictions were challenging when PPI were
strongly attractive due to strong sensitivity to changes in PMF parameter values.
Additional simulations with higher-resolution coarse-grained molecular models
suggest an approach to qualitatively predict cases when anisotropic surface
charge distributions will lead to overall attractive PPI at low ionic strength,
without assumptions regarding electrostatic "patches" or multipole expansions.
PMID- 28422505
TI - Probing Homogeneous Line Broadening in CdSe Nanocrystals Using Multidimensional
Electronic Spectroscopy.
AB - The finite spectral line width of an ensemble of CdSe nanocrystals arises from
size and shape inhomogeneity and the single-nanocrystal spectrum itself. This
line width directly limits the performance of nanocrystal-based devices, yet most
optical measurements cannot resolve the underlying contributions. We use two
dimensional electronic spectroscopy (2D ES) to measure the line width of the band
edge exciton of CdSe nanocrystals as a function of radii and surface chemistry.
We find that the homogeneous width decreases for increasing nanocrystal radius
and that surface chemistry plays a critical role in controlling this line width.
To explore the hypothesis that unpassivated trap states serve to broaden the
homogeneous line width and to explain its size-dependence, we use 3D ES to
identify the spectral signatures of exciton-phonon coupling to optical and
acoustic phonons. We find enhanced coupling to optical phonon modes for
nanocrystals that lack electron-passivating ligands, suggesting that localized
surface charges enhance exciton-phonon coupling via the Frohlich interaction.
Lastly, the data reveal that spectral diffusion contributes negligibly to the
homogeneous line width on subnanosecond time scales.
PMID- 28422504
TI - Integrated Computational Approach to the Electron Paramagnetic Resonance
Characterization of Rigid 310-Helical Peptides with TOAC Nitroxide Spin Labels.
AB - We address the interpretation, via an integrated computational approach, of the
experimental continuous-wave electron paramagnetic resonance (cw-EPR) spectra of
a complete set of conformationally highly restricted, stable 310-helical peptides
from hexa- to nonamers, each bis-labeled with nitroxide radical-containing TOAC
(4-amino-1-oxyl-2,2,6,6-tetramethylpiperidine-4-carboxylic acid) residues. The
usefulness of TOAC for this type of analysis has been shown already to be due to
its cyclic piperidine side chain, which is rigidly connected to the peptide
backbone alpha-carbon. The TOAC alpha-amino acids are separated by two, three,
four, and five intervening residues. This set of compounds has allowed us to
modulate both the radical...radical distance and the relative orientation
parameters. To further validate our conclusion, a comparative analysis has been
carried out on three singly TOAC-labeled peptides of similar main-chain length.
PMID- 28422506
TI - Extra-Large Pore Mesoporous Silica Nanoparticles for Directing in Vivo M2
Macrophage Polarization by Delivering IL-4.
AB - Over the past decade, mesoporous silica nanoparticles (MSNs) smaller than 200 nm
with a high colloidal stability have been extensively studied for systemic drug
delivery. Although small molecule delivery via MSNs has been successful, the
encapsulation of large therapeutic biomolecules, such as proteins or DNA, is
limited due to small pore size of the conventional MSNs obtained by soft
templating. Here, we report the synthesis of mesoporous silica nanoparticles with
extra-large pores (XL-MSNs) and their application to in vivo cytokine delivery
for macrophage polarization. Uniform, size-controllable XL-MSNs with 30 nm extra
large pores were synthesized using organic additives and inorganic seed
nanoparticles. XL-MSNs showed significantly higher loadings for the model
proteins with different molecular weights compared to conventional small pore
MSNs. XL-MSNs were used to deliver IL-4, which is an M2-polarizing cytokine and
very quickly degraded in vivo, to macrophages and polarize them to anti
inflammatory M2 macrophages in vivo. XL-MSNs induced a low level of reactive
oxygen species (ROS) production and no pro-inflammatory cytokines in bone marrow
derived macrophages (BMDMs) and in mice injected intravenously with XL-MSNs. We
found that the injected XL-MSNs were targeted to phagocytic myeloid cells, such
as neutrophils, monocytes, macrophages, and dendritic cells. Finally, we
demonstrated that the injection of IL-4-loaded XL-MSNs successfully triggered M2
macrophage polarization in vivo, suggesting the clinical potential of XL-MSNs for
modulating immune systems via targeted delivery of various cytokines.
PMID- 28422507
TI - Chemo-, Regio-, and Enantioselective Rhodium-Catalyzed Allylation of
Pyridazinones with Terminal Allenes.
AB - The rhodium-catalyzed addition of pyridazinones to terminal allenes furnished the
corresponding branched N2-allylated products in good yields with high regio- and
enantioselectivities. A broad functional group compatibility was observed, and
assorted synthetic transformations of the N-allylpyridazinones led to the
preparation of a small library of N2-functionalized pyridazinones. Labeling
experiments with deuterated substrates provided insights into the underlying
reaction mechanism.
PMID- 28422509
TI - alpha-Glucosidase Inhibitors from Salvia circinata.
AB - A dried infusion prepared from the aerial parts of Salvia circinata did not
provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor
hypoglycemic and antihyperglycemic effects (100-570 mg/kg) when tested in normal
and hyperglycemic mice using acute and oral glucose tolerance tests,
respectively. However, this infusion possessed antihyperglycemic action in vivo
during an oral sucrose tolerance test (31.6-316 mg/kg), suggesting the presence
of alpha-glucosidase inhibitors in S. circinata. Fractionation of a nonpolar
extract of the aerial parts of the plant yielded a new biflavone (1) and four new
neoclerodane diterpenoid glucosides (2-5) along with the known compounds
amarisolide (6), pedalitin (7), apigenin-7-O-beta-d-glucoside (8), and the
flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7-methoxy-4H-chromen-4-one (9).
Compounds 1 and 6-9 were active against mammalian alpha-glucosidases; 6 and 7
were also active against a recombinant alpha-glucosidase from Ruminococcus obeum
and reduced significantly the postprandial peak during an oral sucrose tolerance
test in healthy mice, consistent with their alpha-glucosidase inhibitory
activity. Molecular docking and dynamic studies revealed that compounds 6 and 7
might bind to alpha-glucosidases at the catalytic center of the enzyme.
PMID- 28422508
TI - Nitrile in the Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric
Oxide Synthase Leading to the Development of Potent and Selective 2
Aminoquinoline Inhibitors.
AB - Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat
neurodegenerative disorders, but the development of nNOS inhibitors is often
hindered by poor pharmacokinetics. We previously developed a class of membrane
permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to
decrease off-target binding. However, the resulting compounds had decreased
permeability, low human nNOS activity, and low selectivity versus human eNOS. In
this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives
were synthesized and assayed against purified NOS isoforms. 5-Cyano compounds are
especially potent and selective rat and human nNOS inhibitors. Activity and
selectivity are mediated by the binding of the cyano group to a new auxiliary
pocket in nNOS. Potency was enhanced by methylation of the quinoline and by
introduction of simple chiral moieties, resulting in a combination of hydrophobic
and auxiliary pocket effects that yielded high (~500-fold) n/e selectivity.
Importantly, the Caco-2 assay also revealed improved membrane permeability over
previous compounds.
PMID- 28422510
TI - Halide Perovskites for Tandem Solar Cells.
AB - Perovskite solar cells have become one of the strongest candidates for next
generation solar energy technologies. A myriad of beneficial optoelectronic
properties of the perovskite materials have enabled superb power conversion
efficiencies (PCE) exceeding 22% for a single-junction device. The high PCE
achievable via low processing costs and relatively high variability in optical
properties have opened new possibilities for perovskites in tandem solar cells.
In this Perspective, we will discuss current research trends in fabricating
tandem perovskite-based solar cells in combination with a variety of mature
photovoltaic devices such as organic, silicon, and Cu(In,Ga)(S,Se)2 (CIGS) solar
cells. Characteristic features and present limitations of each tandem cell will
be discussed and elaborated upon. Finally, key issues for further improvement and
the future outlook will be discussed.
PMID- 28422511
TI - Semiclathrate Hydrates in Tri-n-butylphosphine Oxide (TBPO)-Water and TBPO-Water
Methane Systems.
AB - In the present work, we studied semiclathrate hydrates in the TBPO-H2O and TBPO
H2O-CH4 systems. The stoichiometry, temperature, and enthalpy of dissociation of
TBPO semiclathrate hydrate crystals formed in the TBPO-H2O binary system were
found to be TBPO.33.6 +/- 0.9H2O, 280.0 K, and 253.1 +/- 4.7 J g-1, respectively.
The crystal structure determined by single crystal XRD analysis (150 K) was the
orthorhombic with space group Pbam and unit cell parameters a = 19.9313(8) A, b =
23.4660(7) A, and c = 12.1127(5) A. The structural stoichiometry is TBPO.34.5H2O.
The TBPO guest molecules arrangement within the host water framework has been
refined for the first time. The discrepancy between the analytically measured and
structural stoichiometry is likely to be attributed to the structure defects,
which cannot be revealed by the routine single-crystal XRD analysis. The methane
capacity of TBPO + CH4 double hydrate was measured by the thermovolumetric method
in the range 14.9-55.8 wt % TBPO aqueous solution at a methane pressure of 8.5 +/
0.5 MPa and temperature of 274 +/- 1 and 286 +/- 1 K. The maximum included
methane volumes of 61.6-74.6 mL/g were observed for the TBPO + CH4 double
hydrates synthesized from ~26-30 wt % TBPO aqueous solutions. Powder X-ray
diffraction measurements of the hydrate samples used in the thermovolumetric
experiments revealed that the TBPO + CH4 double hydrate has the same structural
characteristics as the simple TBPO hydrate. The study of the Raman spectra of the
TBPO + CH4 double hydrate and TBPO simple hydrate showed that in the TBPO + CH4
double hydrate CH4 molecules selectively occupy the small D cages. The results of
the present study did not confirm the earlier suggestion of the formation of
several structural types of hydrates in the TBPO-H2O system. The obtained results
indicate that the TBPO-H2O binary system has a potential for application in gas
separation and as cold storage and transportation media.
PMID- 28422512
TI - Ultrafast Spectroscopic Investigation of Energy Transfer in Site-Directed Mutants
of the Fenna-Matthews-Olson (FMO) Antenna Complex from Chlorobaculum tepidum.
AB - Ultrafast transient absorption (TA) and time-resolved fluorescence (TRF)
spectroscopic studies were performed on several mutants of the
bacteriochlorophyll (BChl) a-containing Fenna-Matthews-Olson (FMO) complex from
the green sulfur bacterium Chlorobaculum tepidum. These mutants were generated to
perturb a particular BChl a site and determine its effects on the optical
spectroscopic properties of the pigment-protein complex. Measurements conducted
at 77 K under both oxidizing and reducing conditions revealed changes in the
dynamics of the various spectral components as compared to the data set from wild
type FMO. TRF results show that under reducing conditions all FMO samples decay
with a similar lifetime in the ~2 ns range. The oxidized samples revealed varying
fluorescence lifetimes of the terminal BChl a emitter, considerably shorter than
those recorded for the reduced samples, indicating that the quenching mechanism
in wild-type FMO is still present in the mutants. Global fitting of TA data
yielded similar overall results, and in addition, the lifetimes of early decaying
components were determined. Target analyses of TA data for select FMO samples
generated kinetic models that better simulate the TA data. A comparison of the
lifetime of excitonic components for all samples reveals that the mutations
affect mainly the early kinetic components, but not that of the lowest energy
exciton, which reflects the flexibility of energy transfer in FMO.
PMID- 28422513
TI - Reducing Susceptibility to Courtesy Stigma.
AB - In light of the chronic shortage of health professionals willing to care for
HIV/AIDS patients, and rising epidemics in many Muslim countries, this
qualitative study examined susceptibility and resistance to courtesy stigma as
experienced by nurses, doctors, and social workers in Morocco. Forty-nine in
depth interviews provided rich insights into the process of courtesy stigma and
how it is managed, within the context of interactions with Islam, interactions
within the workplace (patients, other health professionals), and interactions
outside the workplace (the general public, friends, and family). Theoretically,
the findings extend understanding of courtesy stigma and the dirty work
literature. The findings also offer practical suggestions for the development of
culturally appropriate strategies to reduce susceptibility to courtesy
stigmatization. This study represents the first to explore courtesy stigma as a
process experienced by health professionals providing HIV/AIDS care in an Islamic
country.
PMID- 28422515
TI - Allergen-induced Increases in Sputum Levels of Group 2 Innate Lymphoid Cells in
Subjects with Asthma.
AB - RATIONALE: Group 2 innate lymphoid cells (ILC2), a major source of type 2
cytokines, initiate eosinophilic inflammatory responses in murine models of
asthma. OBJECTIVES: To investigate the role of ILC2 in allergen-induced airway
eosinophilic responses in subjects with atopy and asthma. METHODS: Using a
diluent-controlled allergen challenge crossover study, where all subjects (n =
10) developed allergen-induced early and late responses, airway eosinophilia, and
increased methacholine airway responsiveness, bone marrow, blood, and sputum
samples were collected before and after inhalation challenge. MEASUREMENTS AND
MAIN RESULTS: ILC2 (lin-FcepsilonRI-CD45+CD127+ST2+) and CD4+T lymphocytes were
enumerated by flow cytometry, as well as intracellular IL-5 and IL-13 expression.
Steroid sensitivity of ILC2 and CD4+ T cells was investigated in vitro. A
significant increase in total, IL-5+, IL-13+, and CRTH2+ ILC2 was found in
sputum, 24 hours after allergen, coincident with a significant decrease in blood
ILC2. Total, IL-5+, and IL-13+, but not CRTH2+, CD4+ T cells significantly
increased at 24 and 48 hours after allergen in sputum. In blood and bone marrow,
only CD4+ cells demonstrated increased activation after allergen. Airway
eosinophilia correlated with IL-5+ ILC2 at all time points and allergen-induced
changes in IL-5+ CD4+ cells at 48 hours after allergen. Dexamethasone
significantly attenuated IL-2- and IL-33-stimulated IL-5 and IL-13 production by
both cell types. CONCLUSIONS: Innate and adaptive immune cells are increased in
the airways associated with allergic asthmatic responses. Total and type 2
cytokine-positive ILC2 are increased only within the airways, whereas CD4+ T
lymphocytes demonstrated local and systemic increases. Steroid sensitivity of
both cells may explain effectiveness of this therapy in those with mild asthma.
PMID- 28422514
TI - Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal
Smoking in Pregnancy.
AB - RATIONALE: Infants whose mothers smoked during pregnancy demonstrate lifelong
decreases in pulmonary function. DNA methylation changes associated with maternal
smoking during pregnancy have been described in placenta and cord blood at
delivery, in fetal lung, and in buccal epithelium and blood during childhood. We
demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier,
NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the
impact of maternal smoking on offspring pulmonary function and decrease the
incidence of wheeze at 1 year of age. OBJECTIVES: To determine whether vitamin C
supplementation reduces changes in offspring methylation in response to maternal
smoking and whether methylation at specific CpGs is also associated with
respiratory outcomes. METHODS: Targeted bisulfite sequencing was performed with a
subset of placentas, cord blood samples, and buccal samples collected during the
NCT00632476 trial followed by independent validation of selected cord blood
differentially methylated regions, using bisulfite amplicon sequencing.
MEASUREMENTS AND MAIN RESULTS: The majority (69.03%) of CpGs with at least 10%
methylation difference between placebo and nonsmoker groups were restored (by at
least 50%) toward nonsmoker levels with vitamin C treatment. A significant
proportion of restored CpGs were associated with phenotypic outcome with greater
enrichment among hypomethylated CpGs. CONCLUSIONS: We identified a pattern of
normalization in DNA methylation by vitamin C supplementation across multiple
loci. The consistency of this pattern across tissues and time suggests a systemic
and persistent effect on offspring DNA methylation. Further work is necessary to
determine how genome-wide changes in DNA methylation may mediate or reflect
persistent effects of maternal smoking on lung function.
PMID- 28422516
TI - Exergaming Through the Eyes of Patients with Heart Failure: A Qualitative Content
Analysis Study.
AB - OBJECTIVE: Exergaming appears to be a promising tool to increase exercise
capacity in patients with chronic heart failure (HF). Therefore, it is important
to obtain more in-depth knowledge about preferences, attitudes, use, and
abilities in regard to exergaming. The aim of this study was to describe the
experiences of patients with HF when using an exergame platform at home.
MATERIALS AND METHODS: A qualitative descriptive study using content analysis was
conducted on interviews with 14 patients with HF (6 women, ages ranging between
56 and 81 years). The patients were recruited from three centers in Sweden
included in a randomized controlled study. These patients had access to an
exergame platform at home and were advised to exergame for 30 minutes per day.
RESULTS: The analysis resulted in three categories describing patients'
experience of exergaming: (1) making exergaming work, (2) added value of
exergaming, and (3) low appeal of exergaming. CONCLUSION: This is the first study
that explores how patients with HF experience using an exergame platform at home.
The study provided important information on what aspects to discuss when
initiating an exergame platform at home and following patients who may want to
use an exergame platform at home. The results also revealed that this technology
may be suitable for some patients, while others prefer other kinds of physical
activity.
PMID- 28422517
TI - Neuropathic pain: a narrative review of etiology, assessment, diagnosis, and
treatment for primary care providers.
AB - BACKGROUND: Neuropathic pain (NeP) is a distinct type of chronic pain that is a
direct result of damage to the nervous system itself. Studies have shown that
training on the topic of chronic pain in medical schools is lacking and many
practitioners are not confident in their ability to effectively manage patients
with such pain. AIMS: The purpose of this narrative review is to provide a brief
high-level overview of NeP for primary healthcare providers that includes a
discussion of mechanisms, prevalence, burden, assessment, and treatment. The
information provided here should help primary care providers better understand
this type of chronic pain.
PMID- 28422518
TI - The Moderating Role of Close versus Distal Peer Injunctive Norms and
Interdependent Self-Construal in the Effects of Descriptive Norms on College
Drinking.
AB - Based on the theory of normative social behavior (Rimal & Real, 2005), this study
examined the effects of descriptive norms, close versus distal peer injunctive
norms, and interdependent self-construal on college students' intentions to
consume alcohol. Results of a cross-sectional study conducted among U.S. college
students (N = 581) found that descriptive norms, close, and distal peer
injunctive norms had independent effects on college students' intentions to
consume alcohol. Furthermore, close peer injunctive norms moderated the effects
of descriptive norms on college students' intentions to consume alcohol and the
interaction showed different patterns among students with a strong and weak
interdependent self-construal. High levels of close peer injunctive norms
weakened the relationship between descriptive norms and intentions to consume
alcohol among students with a strong interdependent self-construal but
strengthened the relationship between descriptive norms and intentions to consume
alcohol among students with a weak interdependent self-construal. Implications of
the findings for norms-based research and college drinking interventions are
discussed.
PMID- 28422519
TI - Spontaneous Hedonic Reactions to Social Media Cues.
AB - Why is it so difficult to resist the desire to use social media? One possibility
is that frequent social media users possess strong and spontaneous hedonic
reactions to social media cues, which, in turn, makes it difficult to resist
social media temptations. In two studies (total N = 200), we investigated less
frequent and frequent social media users' spontaneous hedonic reactions to social
media cues using the Affect Misattribution Procedure-an implicit measure of
affective reactions. Results demonstrated that frequent social media users showed
more favorable affective reactions in response to social media (vs. control)
cues, whereas less-frequent social media users' affective reactions did not
differ between social media and control cues (Studies 1 and 2). Moreover, the
spontaneous hedonic reactions to social media (vs. control) cues were related to
self-reported cravings to use social media and partially accounted for the link
between social media use and social media cravings (Study 2). These findings
suggest that frequent social media users' spontaneous hedonic reactions in
response to social media cues might contribute to their difficulties in resisting
desires to use social media.
PMID- 28422520
TI - Improvement of Performance and Reduction of Fatigue With Low-Level Laser Therapy
in Competitive Cyclists.
AB - Evidence indicates that low-level laser therapy (LLLT) minimizes fatigue effects
on muscle performance. However, the ideal LLLT dosage to improve
athletes'performance during sports activities such as cycling is still unclear.
Therefore, the goal of this study was to investigate the effects of different
LLLT dosages on cyclists'performance in time-to-exhaustion tests. In addition,
the effects of LLLT on the frequency content of the EMG signals to assess fatigue
mechanisms were examined. Twenty male competitive cyclists participated in a
crossover, randomized, double-blind, placebo-controlled trial. They performed an
incremental cycling test to exhaustion (on day 1) followed by 4 time-to
exhaustion tests (on days 2-5) at their individual maximal power output. Before
each time-to-exhaustion test, different dosages of LLLT (135, 270, and 405
J/thigh, respectively) or placebo were applied at the quadriceps muscle
bilaterally. Power output and muscle activation from both lower limbs were
recorded throughout the tests. Increased performance in time-to-exhaustion tests
was observed with the LLLT-135 J (~22 s; P < .01), LLLT-270 J (~13 s; P = .03),
and LLLT-405 J (~13 s; P = .02) compared to placebo (149 +/- 23 s). Although LLLT
270 J and LLLT-405 J did not show significant differences in muscle activation
compared with placebo, LLLT-135 J led to an increased high-frequency content
compared with placebo in both limbs at the end of the exhaustion test (P <= .03).
In conclusion, LLLT increased time to exhaustion in competitive cyclists,
suggesting this intervention as a possible nonpharmacological ergogenic agent in
cycling. Among the different dosages, LLLT-135 J seems to promote the best
effects.
PMID- 28422521
TI - Different approaches to the assessment of adherence and persistence with
cardiovascular-disease preventive medications.
AB - OBJECTIVE: To assess suitability and comparability of the most common methods of
treatment adherence and persistence assessment, as applied to the same pharmacy
dataset. METHODS: Data on drugs prescribed for cardiovascular primary prevention
to participants in the Aragon Workers' Health Study (AWHS) were collected from a
regional electronic drug prescription database. Several different approaches were
used to measure treatment adherence (with the medication possession ratio [MPR])
and proportion of days covered [PDC]) and persistence in new users by therapeutic
subgroup. Defined daily dose (DDD) was used as a proxy of the number of days'
supply, or substituted with surrogate daily dose values. RESULTS: Higher mean
adherence values and proportions of adherent patients were obtained using MPR
versus PDC, with additional differences depending on the approach used. The
proportion of adherent patients was lowest for oral antidiabetics (14.4%-30.6%)
and highest for antihypertensives (70.2%-82.1%). The use of surrogate daily dose
values increased adherence for antidiabetics and statins and decreased adherence
for antihypertensives. After a 1 year follow-up, treatment persistence was
observed for 21.1%, 58.7%, and 29.5% of antidiabetic, antihypertensive and statin
users, respectively. CONCLUSIONS: Our findings indicate that use of multiple
measures of treatment adherence and persistence provides a more complete overview
of medication use patterns, and certain limitations associated with DDD for some
drug groups can be overcome with replacement by surrogate doses. The PDC
indicator seems to provide a more accurate reflection of patient behavior and
treatment continuity than the MPR. Any comparison of adherence/persistence should
always consider the method used, variables analyzed, and corresponding data
collection process.
PMID- 28422522
TI - Molecular Genetic Characterization of a Chinese Family with Severe Split
Hand/Foot Malformation.
AB - AIMS: Split hand/foot malformation (SHFM) is a congenital limb malformation
characterized by underdeveloped or absent central digital rays, clefts of the
hands and feet, and variable syndactyly of the remaining digits. SHFM is a
genetically heterogeneous disease; the aim of this study was to identify
pathogenic variations in a Chinese family with SHFM. MATERIALS AND METHODS:
Haplotype analyses with microsatellite markers covering the five SHFM loci were
performed to localize the causative locus. Real-time quantitative polymerase
chain reaction (qPCR) assays and inverse PCR were performed to determine the copy
number variations and to amplify junction breakpoints in affected individuals.
Candidate genes were further screened for mutations through Sanger sequencing.
RESULTS: A potential haplotype in the SHFM3 locus was shared by all affected
individuals. qPCR and inverse PCR showed a microduplication at chromosome 10q24
spanning 488,859 bp and encompassing five entire genes, LBX1, BTRC, POLL, DPCD,
and FBXW4, that co-segregated with the SHFM phenotype. No coding or splice-site
mutations of these genes were found. CONCLUSION: We determined the molecular
basis of SHFM in a Chinese family by haplotype analysis, qPCR, inverse PCR, and
Sanger sequencing. Our work extends the clinical spectrum of SHFM3; provides a
fine-scale delineation of the chromosomal breakpoints helping to narrow the
critical region of SHFM3; and facilitates an understanding of the mechanisms
underlying abnormal limb development and extraskeletal anomalies.
PMID- 28422523
TI - Can the Lamberts and Lambert Submaximal Cycle Test Reflect Overreaching in
Professional Cyclists?
AB - CONTEXT: The Lamberts and Lambert Submaximal Cycle Test (LSCT) consists of 3
stages during which cyclists cycle for 6 min at 60%, 6 min at 80%, and 3 min at
90% of their maximal heart rate, followed by 1-min recovery. PURPOSE: To
determine if the LSCT is able to reflect a state of functional overreaching in
professional female cyclists during an 8-d training camp and the following
recovery days. METHODS: Six professional female cyclists performed an LSCT on
days 1, 5, and 8 of the training camp and 3 d after the training camp. During
each stage of the LSCT, power output and rating of perceived exertion (RPE) were
determined. Training diaries and Profile of Mood States (POMS) were also
completed. RESULTS: At the middle and the end of the training camp, increased
power output during the 2nd and 3rd stages of the LSCT was accompanied with
increased RPE during these stages and/or the inability to reach 90% of maximal
heart rate. All athletes reported increased feelings of fatigue and muscle
soreness, while changes in energy balance, calculated from the POMS, were less
indicative of a state of overreaching. After 3 d of recovery, all parameters of
the LSCT returned to baseline, indicating a state of functional overreaching
during the training camp. CONCLUSION: The LSCT is able to reflect a state of
overreaching in elite professional female cyclists during an 8-d training camp
and the following recovery days.
PMID- 28422524
TI - Straight-Line and Change-of-Direction Intermittent Running in Professional Soccer
Players.
AB - PURPOSE: To investigate the difference between straight-line (STL) and change-of
direction (COD) intermittent-running exercises in soccer players. METHODS:
Seventeen male professional soccer players performed the agility T test and 6
intermittent-running exercises: 10 s at 130% of maximal aerobic speed (MAS)
alternated with 10 s of rest (10-10), 15 s at 120% of MAS alternated with 15 s of
rest (15-15), and 30 s at 110% of MAS alternated with 30 s of rest (30-30) both
in STL and with COD. All exercises were monitored using a global positioning
system. Heart rate was measured during exercises, and rating of perceived
exertion (RPE) was collected postexercise. The difference (Delta) between covered
distance in STL and COD exercises at a similar load was calculated, and
relationships between T test and Delta distance were analyzed. RESULTS: COD
intermittent exercises showed a significantly decreased distance covered and an
increase in the number of accelerations, peak heart rate, and RPE compared with
STL intermittent exercises at a similar load. High relationships were observed
between T-test performance and Delta distance in 10-10 (r = .72, P < .01) and 15
15 (r = .77, P < .01), whereas no significant relationships were observed between
T-test performance and Delta distance in 30-30 (r = -.37, P = .2). CONCLUSION:
Intermittent COD exercises were associated with higher acceleration, peak heart
rate, and RPE than STL during 10-10 and 15-15 exercises. The ability to rapidly
change direction is crucial to perform intense sport-specific running in
professional soccer players.
PMID- 28422525
TI - Soccer Match Play as an Important Component of the Power-Training Stimulus in
Premier League Players.
AB - PURPOSE: Competitive match play is a dominant component of the physical load
completed by soccer players in a training microcycle. Characterizing the temporal
disruption in homeostasis that follows exercise may provide some insight on the
potential for match play to elicit an adaptive response. METHODS: Countermovement
jump (CMJ) performance was characterized 3 d postmatch for 15 outfield players
from an English Premier League soccer team (age 25.8 +/- 4.1 y, stature 1.78 +/-
0.08 m, body mass: 71.7 +/- 9.1 kg) across a season. These players were
classified as either starters (n = 9) or nonstarters (n = 6), according to their
average individual playing time (more or less than 60 min/match). Linear mixed
models were used to investigate the influence of indicators of match activity
(total distance covered [TD] and high-intensity running distance [HI]) on CMJ
height and peak power (PP). RESULTS: Starting players covered much greater TD (ES
= 1.5) and HI (ES = 1.4) than nonstarters. Furthermore, there was a possible
positive effect of HI on CMJ height and PP. This relationship suggests that an
additional 0.6 km of HI would increase CMJ height and PP by slightly more than
the smallest-worthwhile-change values of 0.6 cm and 1.0 W/kg, respectively. This
small yet practically relevant increase in performance may suggest that match
play, more specifically the intense activities that are associated with the
match, provides a physiological stimulus for neuromuscular adaptation.
CONCLUSIONS: These data may have implications for the preparation of soccer
squads, especially the training requirements of starting and nonstarting players.
PMID- 28422526
TI - Acupuncture on Renal Function in Patients with Chronic Kidney Disease: A Single
Blinded, Randomized, Preliminary Controlled Study.
AB - OBJECTIVE: To evaluate the feasibility effect of acupuncture on renal function in
patients with chronic kidney disease (CKD). METHODS: In total, 59 patients with
CKD were randomized into acupuncture (AG; n = 30) and sham acupuncture (CG; n =
29) treatment groups. In the AG, acupuncture was applied to bilateral Hegu (LI4),
Zusanli (ST36), and Taixi (KI3) to obtain qi, and electroacupuncture (2 Hz) was
applied to two acupoint pairs (right Zusanli and Taixi and left Zusanli and
Taixi) once per week for 12 weeks. In the CG, the acupuncture methods were
identical to in the AG, and the acupuncture needle was applied to the
subcutaneous layer at 1.5 cm lateral to the aforementioned acupoints, without
electrical discharge. The levels of serum creatinine and estimated glomerular
filtration rate (eGFR) were measured at 3 months (observation period; O),
immediately before the acupuncture treatment (baseline; B), at 12 weeks (after
treatment completion; T12), and at the 3-month follow-up (postacupuncture
treatment; P). RESULTS: In total, 53 patients (AG, n = 28; CG, n = 25) with CKD
completed the trial. The serum creatinine levels at baseline (B) were 1.45 mg/dL
in the AG and 1.67 mg/dL in the CG (p = 0.1298). Furthermore, the change in serum
creatinine levels after the acupuncture treatment (T12) was 1.41 mg/dL in the AG
and 1.65 mg/dL in the CG (p = 0.0489). The eGFR at baseline was 51.85 mL/min/1.73
m2 in the AG and 42.50 mL/min/1.73 m2 in the CG (p = 0.0855). The change in the
eGFR after the acupuncture treatment was 54.50 mL/min/1.73 m2 in the AG and 43.60
mL/min/1.73 m2 in the CG (p = 0.0470). CONCLUSION: Acupuncture at bilateral Hegu,
Zusanli, and Taixi for 12 weeks reduced creatinine levels and increased eGFR
levels. The study only provided a feasibility method for the treatment of
patients with CKD. However, the results of this preliminary study warrant further
investigation.
PMID- 28422527
TI - Attitudes Toward Stimulant Treatment of Offspring of Adult Patients with
Attention-Deficit/Hyperactivity Disorder.
AB - AIM: The objective of this study was to investigate how adult patients with
attention-deficit/hyperactivity disorder viewed the testing and use of stimulants
in their children. METHODS: Using a qualitative approach, we interviewed 32
outpatients from a special care unit of a university hospital. RESULTS: Emerging
themes centered around concerns about the right age to test children and opinions
about stimulant treatment ranging from unreserved agreement to reluctance, as
well as the need for a shared decision with the child. CONCLUSIONS: Our results
suggest that better psychoeducational programs are needed, especially for adults
with attention-deficit/hyperactivity disorder, in which long-term consequences of
the disorder, areas of impairment, and possible treatment effects in their
children are explained and concerns about unknown side effects and the right time
to test and treat are addressed.
PMID- 28422528
TI - Effect of Psychopharmacotherapy on Body Mass Index Among Children and Adolescents
with Bipolar Disorders.
AB - OBJECTIVE: To assess the long-term effect of all treatment options for pediatric
bipolar disorders on body mass index (BMI) and to explore individual
characteristics associated with less BMI increase during psychotropic medication
exposures. METHODS: A retrospective cohort study was conducted by using the 1995
to 2010 General Electric Electronic Medical Record database. Individuals aged 18
years or younger who had a new bipolar disorder episode were identified.
Treatment exposure was defined based on the medication regimens patients
received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer
(MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD
polytherapy, MS+AD polytherapy, and no treatment. Both treatment exposure and BMI
were coded as time varying, which could change from month to month. According to
the duration of treatment and the availability of BMI measures, individuals were
followed for up to 3, 6, 9, and 12 months since the treatment initiation.
Repeated-measures mixed models were applied to compare the impact of different
medication regimens and the length of drug exposure on BMI after adjusting for
the baseline BMI, sociodemographic factors, comorbidities, and psychotherapy.
RESULTS: A total of 2299 treated and 4544 untreated children and adolescents who
met the inclusion criteria were identified. Analysis using repeated-measures
mixed models showed that those on AT monotherapy (the reference group) had a
gradually diminished, but statistically significant, monthly increase in BMI
during all durations of drug exposure (3 months: 0.36 kg/m2, 6 months: 0.20
kg/m2, 9 months: 0.17 kg/m2, and 12 months: 0.16 kg/m2). As compared with AT
monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy,
and no treatment was significantly less at all time points, indicating less steep
slopes of BMI change over time compared with AT monotherapy, especially during
the short-term exposure. The combinations of AT with other psychotropic
medications (ATMS, ATAD) were associated with a similar BMI increase as AT
monotherapy. Individual characteristics found to be associated with a less
increase in BMI during psychotropic medication exposure were being younger and
having a higher baseline BMI. CONCLUSION: The long-term use of atypical
antipsychotics, both as monotherapy or in combination with other psychotropic
medications in children and adolescents with bipolar disorder, was associated
with a steady and cumulative increase in BMI.
PMID- 28422529
TI - Implant compositions for the unidirectional delivery of drugs to the brain.
AB - The overall objective of this study was to design and characterize the properties
of a bioadhesive trilayer sustained-release implant device for the unidirectional
local delivery of anticancer compounds to the brain following the removal of
glioblastoma multiforme tumors. Using acetaminophen as a model drug compound, we
compressed trilayer wafers that contained (i) a bioadhesive layer, (ii) a drug
layer that contained a lipid and a pore-forming hydrophilic polymer, and (iii) a
third layer comprising a lipid substance. To maintain a unidirectional pathway of
drug release from these trilayer wafers, the edges and the surface lipophilic
layer were coated with molten wax followed by cooling of the wafer. These wafers
were subsequently heat cured to promote interlayer adhesion in the device.
Polyethylene oxide was utilized both as the bioadhesive layer and the pore
forming hydrophilic polymer. Glyceryl behenate was employed as the lipid. The
drug release properties of the trilayer wafer were a function of (i) the
molecular weight and concentration of polyethylene oxide in the drug-containing
lipid layer, (ii) the presence of the bioadhesive layer on the wafer, and (iii)
the lipid coating applied to the top and sides of the delivery system. The
unidirectional release of the drug occurred from the device through the
bioadhesive layer, and zero-order release kinetics resulted over a 10-day period
after a 3-day lag time. During this period, <10% of the drug had been released
from the wafer. All of the drug was released by 21 days.
PMID- 28422530
TI - Physiological Changes Following Competition in Male and Female Physique Athletes:
A Pilot Study.
AB - The purpose of the current study was to evaluate changes in body composition,
metabolic rate, and hormones during postcompetition recovery. Data were collected
from natural physique athletes (7 male/8 female) within one week before (T1)
competition, within one week after (T2), and 4-6 weeks after (T3) competition.
Measures included body composition (fat mass [FM] and lean mass [LM] from
ultrasongraphy), resting metabolic rate (RMR; indirect calorimetry), and salivary
leptin, testosterone, cortisol, ghrelin, and insulin. Total body water (TBW;
bioelectrical impedance spectroscopy) was measured at T1 and T2 in a subsample (n
= 8) of athletes. Significant (p < .05) changes were observed for weight (T1 =
65.4 +/- 12.2 kg, T2 = 67.4 +/- 12.6, T3 = 69.3 +/- 13.4; T3 > T2 > T1), LM (T1 =
57.6 +/- 13.9 kg, T2 = 59.4 +/- 14.2, T3 = 59.3 +/- 14.2; T2 and T3 > T1), and FM
(T1 = 7.7 +/- 4.4 kg, T2 = 8.0 +/- 4.4, T3 = 10.0 +/- 6.2; T3 > T1 and T2). TBW
increased from T1 to T2 (Delta=1.9 +/- 1.3 L, p < .01). RMR increased from
baseline (1612 +/- 266 kcal/day; 92.0% of predicted) to T2 (1881 +/- 329, 105.3%;
p < .01) and T3 (1778 +/- 257, 99.6%; p < .001). Cortisol was higher (p < .05) at
T2 (0.41 +/- 0.31 MUg/dL) than T1 (0.34 +/- 0.31) and T3 (0.35 +/- 0.27). Male
testosterone at T3 (186.6 +/- 41.3 pg/mL) was greater than T2 (148.0 +/- 44.6, p
= .04). RMR changes were associated (p <= .05) with change in body fat percent
(DeltaBF%; r = .59) and T3 protein intake (r= .60); male testosterone changes
were inversely associated (p<= .05) with DeltaBF%, DeltaFM, and Deltaweight (r=
0.81--0.88). TBW increased within days of competition. Precompetition RMR
suppression appeared to be variable and markedly reversed by overfeeding, and
reverted toward normal levels following competition. RMR and male testosterone
increased while FM was preferentially gained 4-6 weeks postcompetition.
PMID- 28422531
TI - Femoroacetabular Impingement in Professional Football Players: Return to Play and
Predictors of Career Length After Hip Arthroscopy.
AB - BACKGROUND: Previous studies have shown hip arthroscopy to be a highly effective
treatment for symptomatic femoroacetabular impingement (FAI) in a wide range of
athletes; however, the rate of return to play and length of career after hip
arthroscopy in professional football players are unknown. PURPOSE: To determine
how many athletes returned to professional football and the number of seasons
they played after surgery. STUDY DESIGN: Case series; Level of evidence, 4.
METHODS: Fifty-one professional football players (60 hips) underwent hip
arthroscopy for FAI between 2000 and 2014 by a single surgeon. Return to play was
defined as competing in a preseason or regular season professional football game
after surgery. Data were retrospectively obtained for each player from NFL.com ,
ESPN.com , individual team websites, and/or CFL.ca . RESULTS: We found that 87%
(52/60) of the arthroscopic procedures allowed professional football players to
return to play in a preseason or regular season game. Athletes who returned
played an average of 38 games during 3.2 seasons after arthroscopy, with an
average total career length of 7.4 seasons. Ninety-two percent (48/52) of players
who returned had a minimum total career length of 3 years. When participants were
analyzed by position, linemen were less likely to return after hip arthroscopy
compared with other players (odds ratio 5.6; 95% CI, 1.1-35; P = .04). All
quarterbacks and tight ends returned to play after surgery. No significant
difference in return to play rate was found between athletes who underwent
microfracture and those who did not (25% vs 38%, P = .698). CONCLUSION: Hip
arthroscopy for treatment of FAI and associated pathologic abnormalities in
professional football players resulted in a high rate of return to play. The
study's findings demonstrate that 87% of the arthroscopic procedures allowed
professional football players to return to play, linemen were less likely to
return compared with other positions, and the presence of microfracture did not
significantly affect the return to play rate. These findings support hip
arthroscopy as an effective procedure to treat FAI and related pathologic
abnormalities in the professional football player, and this information is
important for proper counseling of athletes with FAI.
PMID- 28422532
TI - Effects of Postexercise Protein Intake on Muscle Mass and Strength During
Resistance Training: Is There an Optimal Ratio Between Fast and Slow Proteins?
AB - While effects of the two classes of proteins found in milk (i.e., soluble
proteins, including whey, and casein) on muscle protein synthesis have been well
investigated after a single bout of resistance exercise (RE), the combined
effects of these two proteins on the muscle responses to resistance training (RT)
have not yet been investigated. Therefore, the aim of this study was to examine
the effects of protein supplementation varying by the ratio between milk soluble
proteins (fast-digested protein) and casein (slow-digested protein) on the muscle
to a 9-week RT program. In a double-blind protocol, 31 resistance-trained men,
were assigned to 3 groups receiving a drink containing 20g of protein comprising
either 100% of fast protein (FP(100), n = 10), 50% of fast and 50% of slow
proteins (FP(50), n = 11) or 20% of fast protein and 80% of casein (FP(20), n =
10) at the end of training bouts. Body composition (DXA), and maximal strength in
dynamic and isometric were analyzed before and after RT. Moreover, blood plasma
aminoacidemia kinetic after RE was measured. The results showed a higher leucine
bioavailability after ingestion of FP(100) and FP(50) drinks, when compared with
FP(20) (p< .05). However, the RT-induced changes in lean body mass (p < .01),
dynamic (p < .01), and isometric muscle strength (p < .05) increased similarly in
all experimental groups. To conclude, compared with the FP(20) group, the higher
rise in plasma amino acids following the ingestion of FP(100) and FP(50) did not
lead to higher muscle long-term adaptations.
PMID- 28422533
TI - Effect of Resistance Training Systems on Oxidative Stress in Older Women.
AB - The purpose of this study was to investigate the effect of two different
resistance training (RT) systems on oxidative stress biomarkers in older women.
Fifty-nine older women (67.9 +/- 5.0 years) were randomly assigned to one of
three groups. Two training groups performed an 8 week RT program either in
traditional (TD, n = 20) or a pyramid (PR, n = 20) system 3 times per week, or a
control group (CG, n = 19). The TD program consisted of 3 sets of 8-12 RM with
constant load for the 3 sets, whereas the PR training consisted of 3 sets of
12/10/8 RM with incremental loads for each set. As compared with the CG, both TD
and PR achieved upregulation of the antioxidant system as evidenced by higher (p
< .05) values of total radical-trapping antioxidant parameter plasma
concentration after intervention (TD= 930.4 +/- 160.0 umolTrolox, PR= 977.8 +/-
145.2 umolTrolox, CG= 794.4 +/- 130.2 umolTrolox). For the protein oxidation
adducts, TD and PR presented lower (p < .05) scores compared with CG (TD= 91.2 +/
25.0 umol/L, PR= 93.0 +/- 30.3 umol/L, CG= 111.0 +/- 20.4 umol/L). However,
there were no differences (p < .05) between trained groups in the antioxidant
capacity markers and in the protein oxidation adducts markers. The results
suggest that 8 weeks of progressive RT promotes an improvement in markers of
oxidative stress in older women independent of the load-management RT system.
PMID- 28422534
TI - In Situ Sampling of Relative Dust Devil Particle Loads and Their Vertical Grain
Size Distributions.
AB - During a field campaign in the Sahara Desert in southern Morocco, spring 2012, we
sampled the vertical grain size distribution of two active dust devils that
exhibited different dimensions and intensities. With these in situ samples of
grains in the vortices, it was possible to derive detailed vertical grain size
distributions and measurements of the lifted relative particle load. Measurements
of the two dust devils show that the majority of all lifted particles were only
lifted within the first meter (~46.5% and ~61% of all particles; ~76.5 wt % and
~89 wt % of the relative particle load). Furthermore, ~69% and ~82% of all lifted
sand grains occurred in the first meter of the dust devils, indicating the
occurrence of "sand skirts." Both sampled dust devils were relatively small (~15
m and ~4-5 m in diameter) compared to dust devils in surrounding regions;
nevertheless, measurements show that ~58.5% to 73.5% of all lifted particles were
small enough to go into suspension (<31 MUm, depending on the used grain size
classification). This relatively high amount represents only ~0.05 to 0.15 wt %
of the lifted particle load. Larger dust devils probably entrain larger amounts
of fine-grained material into the atmosphere, which can have an influence on the
climate. Furthermore, our results indicate that the composition of the surface,
on which the dust devils evolved, also had an influence on the particle load
composition of the dust devil vortices. The internal particle load structure of
both sampled dust devils was comparable related to their vertical grain size
distribution and relative particle load, although both dust devils differed in
their dimensions and intensities. A general trend of decreasing grain sizes with
height was also detected.
PMID- 28422535
TI - Comparison between normal saline and Ringer's acetate in bipolar transurethral
resection of the prostate.
AB - OBJECTIVE: The standard surgical treatment for benign prostatic hypertrophy (BPH)
is transurethral resection of the prostate (TURP). The aim of this study was to
compare normal saline (NS) (0.9% sodium chloride) and Ringer's acetate (RA) as
irrigation fluid with regard to visibility, resection feasibility, coagulation
and bleeding in bipolar TURP. MATERIALS AND METHODS: Twenty patients (mean age 70
years) who were diagnosed with BPH were recruited to the study. The first three 3
liter bags of irrigation fluid contained either NS or RA and were administered in
a randomized fashion. The surgeon assessed visibility, bleeding, coagulation,
resection efficacy and overall outcome after each 3 liter bag on a scale of 1-10.
RESULTS: The results disclosed only marginal differences between the two fluids
with regard to the recorded parameters. All of the differences lacked statistical
significance (p > .05). CONCLUSION: RA can be used as an irrigation fluid in
bipolar TURP with no obvious difference in comparison with NS.
PMID- 28422536
TI - Impact of Lifestyle Strategies on Longer-Term Physical Activity and Weight.
AB - BACKGROUND: Lifestyle interventions promote increased physical activity (PA) and
weight loss; however, relapse to sedentary behavior and weight regain are common.
METHODS: We analyzed baseline and 24-month data from participants in the Slow the
Adverse Vascular Effects (SAVE) study. SAVE included an 18-month behavioral
intervention. At 24 months, participants completed a survey about lifestyle
strategies used in past 6 months. PA levels were assessed with the Modifiable
Activity Questionnaire. We compared change in weight, BMI, and PA from baseline
to 24 months by use of strategies vs. no use. RESULTS: 214 participants (61%)
completed 24-month visit. 74% were female and 86% were white. At 24 months, 65%
used self-monitoring, 67% group/commercial support, 94% other behavioral skills,
and 27% used professional support within past 6 months. At 24 months,
participants who used self-monitoring (5.2 vs. -0.8 MET-hr/wk; P = .001) and
group/commercial support (4.3 vs. 0 MET-hrs/wk; P = .01) had greater PA increases
compared with those who did not use strategies. Participants who used other
behavioral strategies had a significantly greater percent decrease in weight than
those who did not. CONCLUSIONS: Of the lifestyle strategies used following
intervention, self-monitoring and group/commercial support may be particularly
important in longer-term PA levels.
PMID- 28422538
TI - An Examination of Exercise-Induced Feeling States and Their Association With
Future Participation in Physical Activity Among Older Adults.
AB - Although exercise-induced feeling states may play a role in driving future
behavior, their role in relation to older adults' participation in physical
activity (PA) has seldom been considered. The objectives of this study were to
describe changes in older adults' feeling states during exercise, and examine if
levels of and changes in feeling states predicted their future participation in
PA. Self-reported data on feeling states were collected from 82 older adults
immediately before, during, and after a moderate-intensity exercise session, and
on participation in PA 1 month later. Data were analyzed using latent growth
modeling. Feelings of revitalization, positive engagement, and tranquility
decreased during exercise, whereas feelings of physical exhaustion increased.
Feelings of revitalization immediately before the exercise session predicted
future participation in PA; changes in feeling states did not. This study does
not provide empirical evidence that older adults' exercise-induced feeling states
predict their future participation in PA.
PMID- 28422537
TI - Morbidity and Mortality Associated with Prehospital "Lift-assist" Calls.
AB - INTRODUCTION: When an individual requires assistance with mobilization, emergency
medical services (EMS) may be called. If a patient does not receive treatment on
scene and is not transported to hospital, these are referred to as "Lift Assist"
(LA) calls. It is possible this need for assistance represents a subtle onset of
a disease process or decline in function. Without recognition or treatment, the
patient may be at risk for recurrent falls, repeat EMS visits or worsening
illness. OBJECTIVE: To examine the 14-day morbidity and mortality associated with
LA calls and determine factors that are associated with increased risk of these
outcomes. METHODS: All LA calls from a single EMS agency were collected over a
one year study period (January-December 2013). Calls were linked with hospital
records to determine if LA patients had a subsequent visit to the emergency
department (ED), admission, or death within 14 days of the LA call. Logistic
regression analyses were completed to determine factors predicting ED visit or
hospital admission within 14 days of the LA call. RESULTS: Of 42,055 EMS calls,
804 (1.9%) were LAs. These calls were for 414 individuals; 298 (72%) patients had
1 LA, and 116 (28%) patients had >1 LA call. There were 169 (21%) ED visits, 93
(11.6%) hospital admissions and 9 (1.1%) deaths within 14 days of a LA call.
Patient age (p = 0.025) significantly predicted ED visit. Patient age (p = 0.006)
and an Ambulance Call Record missing at least 1 vital sign (p = 0.038)
significantly predicted hospital admission. CONCLUSIONS: LA calls are associated
with short-term morbidity and mortality. Patient age was found to be associated
with these outcomes. These calls may be early indicators of problems requiring
comprehensive medical evaluation and thus further factors associated with poor
outcomes should be determined.
PMID- 28422540
TI - Evaluating Barriers to Bystander CPR among Laypersons before and after
Compression-only CPR Training.
AB - OBJECTIVE: Bystander CPR is an essential part of out-of-hospital cardiac arrest
(OHCA) survival. EMS and public safety jurisdictions have embraced initiatives to
teach compression-only CPR to laypersons in order to increase rates of bystander
CPR. We examined barriers to bystander CPR amongst laypersons participating in
community compression-only CPR training and the ability of the training to
alleviate these barriers. The barriers analyzed include fear of litigation, risk
of disease transmission, fear of hurting someone as a result of doing CPR when
unnecessary, and fear of hurting someone as a result of doing CPR incorrectly.
METHODS: Laypersons attending community compression-only CPR training were
administered surveys before and after community CPR training. Data were analyzed
via standard statistical analyses. RESULTS: A total of 238 surveys were collected
and analyzed between September 2015 and January 2016. The most common reported
motivation for attending CPR training was "to be prepared/just in case" followed
by "infant or child at home." Respondents reported that they were significantly
more likely to perform CPR on a family member than a stranger in both pre-and
post-training responses. Nevertheless, reported self-confidence in and likelihood
of doing CPR on both family and strangers increased from pre-training to post
training. There was a statistically significant decrease in reported likelihood
of all four barriers to prevent respondents from performing bystander CPR when
pre-training responses were compared to post-training responses. Previous CPR
training and history of having witnessed a sudden cardiac arrest (SCA) were both
associated with decreased barriers to CPR, but previous training had no effect on
reported likelihood of or confidence in performing CPR. CONCLUSION: The training
initiative studied significantly reduced the reported likelihood of all barriers
studied to prevent respondents from performing bystander CPR and also increased
the reported confidence in doing CPR and likelihood of doing CPR on both
strangers and family. However, it did not alleviate the pre-training discrepancy
between likelihood of performing CPR on strangers versus family. Previous CPR
training or certification had no impact on likelihood of or confidence in
performing CPR.
PMID- 28422539
TI - The Effect of Nitrate Supplementation on Cycling Performance in the Heat in Well
Trained Cyclists.
AB - PURPOSE: To determine the effect of [Formula: see text] consumption on measures
of perception, thermoregulation, and cycling performance in hot conditions.
METHODS: In a randomized, double-blind, crossover design, 8 well-trained cyclists
(mean +/- SD age 25 +/- 8 y, [Formula: see text] peak 64 +/- 5 mL . kg-1 . min-1)
performed 2 separate trials in hot (35 degrees C, 60% relative humidity)
environments, having ingested either 140 mL [Formula: see text]-rich beetroot
juice ~8 mmol [Formula: see text] (NIT) or placebo (PLA) daily for 3 d with a 7-d
washout period separating trials. Trials consisted of 2 * 10-min bouts at 40% and
60% peak power output (PPO) to determine physiological and perceptual responses
to the heat, followed by a 4-km cycling time trial. RESULTS: Basal [nitrite] was
substantially elevated in NIT (2.70 +/- 0.98 uM) vs PLA (1.10 +/- 0.61 uM),
resulting in a most likely (ES = 1.58 +/- 0.93) increase after 3 d. There was a
very likely trivial increase in rectal temperature in NIT at 40% (PLA 37.4
degrees C +/- 0.2 degrees C vs NIT 37.5 degrees C +/- 0.3 degrees C, 0.1 degrees
C +/- 0.2 degrees C) and 60% (PLA 37.8 degrees C +/- 0.2 degrees C vs NIT 37.9
degrees C +/- 0.3 degrees C, 0.1 degrees C +/- 0.2 degrees C) PPO. Cycling
performance was similar between trials (PLA 336 +/- 45 W vs NIT 337 +/- 50 W, CV
+/- 95%CL; 0.2% +/- 2.5%). Outcomes for heart rate and perceptual measures were
unclear across the majority of time points. CONCLUSIONS: Three days of [Formula:
see text] supplementation resulted in small increases in rectal temperature
during low- to moderate-intensity exercise, but this did not appear to influence
4-km cycling time-trial performance in hot climates.
PMID- 28422541
TI - Evaluation of the Implementation of the Trauma Triage and Destination Plan on the
Field Triage of Injured Patients in North Carolina.
AB - OBJECTIVE: Timely triage and appropriate destination decision making for injured
patients are central challenges faced by emergency medical services (EMS)
systems. In 2010, North Carolina (NC) adopted a statewide Trauma Triage and
Destination Plan (TTDP) based on the CDC's Field Triage Guidelines to better
address these challenges. We sought to characterize the implementation of these
guidelines by quantifying their effect on multiple metrics of patient care.
METHODS: We employed a retrospective pre-post study design utilizing a statewide
EMS medical record database. We assessed several metrics of patient care
including changes in destination choice, appropriateness of EMS destination,
transit time to first hospital, transit time to definitive care, and others-in a
six-month period in the year before and after the implementation of the
guidelines. RESULTS: We evaluated a total of 190,307 EMS encounters pre- (n =
93,927) and post-implementation (n = 96,380). Among all patients, there was not a
significant difference in the percentage transported to a community hospital or
Level I, II, or III trauma center as their first destination. Among those
patients meeting TTDP guidelines for transport to a trauma center, the number
transported to a Level I or II trauma center decreased 1.0% from 30.6% (n =
2,911) to 29.6% (n = 2,954) (95% CI: -0.2%, 2.2%). Those transported to a Level I
trauma center decreased 0.4% from 21.2% to 20.8% in the post-period (95% CI:
0.7%, 1.5%). There were also no significant changes in EMS scene times (14.0 pre
, 14.1 post-) and transport times (12.9 pre-, 13.0 post-). While scene distance
from a Level I trauma center showed a decreased likelihood of transport to that
center, there was an overall post-implementation increase of 2.5% from 18.0% to
20.5% (95% CI: -3.6%, -1.3%) in transport to a Level I trauma center among
patients meeting anatomic criteria across all distance ranges. CONCLUSIONS: We
found that implementation of region-specific destination plans based on the Field
Triage Guidelines had little effect on selected hospital destination, scene
times, transport times, and other metrics of EMS decision making and
effectiveness. We suspect this is due to delays in information dissemination and
adoption by field providers.
PMID- 28422542
TI - Routine Yoga Practice Impacts Whole Body Protein Utilization in Healthy Women.
AB - Whole body protein utilization (WBPU), which includes flux (Q), protein synthesis
(PS), protein breakdown (PB), and whole body protein balance (WBPB), provides
insight regarding muscle mass, a criterion for sarcopenia. To characterize yoga's
impact on WBPU, body composition and functional measures in healthy (50-65 years)
women. WBPU and functional measures were compared between women who routinely
practiced yoga (YOGA; n = 7) and nonactive counterparts (CON; n = 8). Q (0.61 +/-
0.06 vs. 0.78 +/- 0.07, p = .04), PS (3.07 +/- 0.37 vs. 4.17 +/- 0.40, p = .03),
PB (2.59 +/- 0.48 vs. 3.80 +/- 0.48, p = .05) were lower, and lean body mass
higher (64 +/- 1 vs. 58 +/- 2%, p <= .01) for YOGA vs. CON, respectively. WBPB
and functional measures were similar. Routine yoga practice influenced WBPU in
healthy older women. Study findings are novel and provide a basis for future
investigations evaluating long-term benefits of yoga as an alternative mode of
exercise for maintaining muscle mass in support of active aging.
PMID- 28422544
TI - Effects of Balance-Coordination, Strengthening, and Aerobic Exercises to Prevent
Falls in Postmenopausal Patients With Osteoporosis: A 6-Month Randomized Parallel
Prospective Study.
AB - Osteoporosis is a systemic disease characterized by the increase of bone
fragility and fracture risk. Postmenopausal female osteoporotic patients were
randomized into three groups: balance and coordination, strengthening, and
aerobic exercise. The exercise programs were performed for 12 weeks, 1 hr each
day for 3 days of the week. Patients were followed-up for 12 weeks after the
initial intervention. After the exercise program, patients continued their daily
life activities and were called back to the clinic for additional testing after
12 weeks. Static and dynamic balance measurements and pain and life quality
assessments were performed at enrollment, and at the 12th and 24th weeks.
Significant improvements in both the Timed Up and Go test and Berg Balance Scale
values at the 12th week were only observed in the balance-coordination group.
There were statistically significant improvements in night and daytime pain
visual analog scale scores at the 12th and 24th weeks in the strengthening
exercise group. No patient experienced falling during the 24th week follow-up.
The strengthening exercises were observed to be more effective in pain reduction,
and balance and coordination exercises were found to be more effective in
improvement of static and dynamic balance.
PMID- 28422543
TI - Newer Insights into the Antidiarrheal Effects of Acacia catechu Willd. Extract in
Guinea Pig.
AB - Acacia catechu Willd. is a plant diffused in India and other Asian countries,
where it is used as a traditional medicine for the treatment of several ailments
including diarrhea, one of the most common pathologies worldwide. In this study,
we determined the chemical composition of Acacia catechu Willd. extract (AC) and
evaluated its effect on spontaneous and induced contractility in isolated guinea
pig ileum and proximal colon. Preliminary data about its antimicrobial effect
against some pathogen agents versus some microbiota intestinal strain have been
also reported. Chemical analysis revealed the presence of catechins, such as (-)
Epicatechin and (+)-Catechin. AC extract reduced frequency and amplitude of colon
smooth muscle spontaneous contractility, in a concentration-dependent manner. A
weaker effect of the extract was exerted toward ileum smooth muscle spontaneous
contractility. The observed calcium antagonistic effect was more potent in
proximal colon than in ileum. The extract showed a noncompetitive reversible
antagonism to carbachol, both in proximal colon and ileum, with a higher potency
in proximal colon. The antimicrobial effects of AC extract were observed toward
Campylobacter jejuni, Escherichia coli, and Salmonella spp., while Bifido and
Lactobacillus were not affected by treatment. These effects, however, occurred at
concentrations fivefold higher than those inhibiting ileum and colon
contractility. In conclusion, our results suggest that AC affects intestinal
contractility without affecting intestinal bacterial flora and this may result in
clinical benefits in patients suffering from nonbacterial diarrhea.
PMID- 28422545
TI - Response to Aslankurt et al. re: "Safety Profile of Stromal Hydration of Clear
Corneal Incisions with Cefuroxime in the Mouse Model".
PMID- 28422546
TI - No Compromise of Competition Sleep Compared With Habitual Sleep in Elite
Australian Footballers.
AB - PURPOSE: To assess the impact of match-start time and days relative to match
compared with the habitual sleep characteristics of elite Australian Football
(AF) players. METHODS: 45 elite male AF players were assessed during the
preseason (habitual) and across 4 home matches during the season. Players wore an
activity monitor the night before (-1), night of (0), 1 night after (+1), and 2
nights (+2) after each match and completed a self-reported rating of sleep
quality. A 2-way ANOVA with Tukey post hoc was used to determine differences in
sleep characteristics between match-start times and days relative to the match.
Two-way nested ANOVA was conducted to examine differences between competition and
habitual phases. Effect size +/- 90% confidence interval (ES +/- 90% CI) was
calculated to quantify the magnitude of pairwise differences. RESULTS:
Differences observed in sleep-onset latency (ES = 0.11 +/- 0.16), sleep rating
(ES = 0.08 +/- 0.14), and sleep duration (ES = 0.08 +/- 0.01) between competition
and habitual periods were trivial. Sleep efficiency was almost certainly higher
during competition than habitual, but this was not reflected in the subjective
rating of sleep quality. CONCLUSIONS: Elite AF competition does not cause
substantial disruption to sleep characteristics compared with habitual sleep.
While match-start time has some impact on sleep variables, it appears that the
match itself is more of a disruption than the start time. Subjective ratings of
sleep from well-being questionnaires appear limited in their ability to
accurately provide an indication of sleep quality.
PMID- 28422547
TI - Active Travel Behavior in a Border Region of Texas and New Mexico: Motivators,
Deterrents, and Characteristics.
AB - BACKGROUND: Active travel has been linked with improved transportation and health
outcomes, such as reduced traffic congestion and air pollution, improved
mobility, accessibility, and equity, and increased physical and mental health.
The purpose of this study was to better understand active travel characteristics,
motivators, and deterrents in the El Paso, TX, region. METHODS: A multimodal
transportation survey brought together elements of transportation and health,
with a focus on attitudinal characteristics. The analysis consisted of an initial
descriptive analysis, spatial analysis, and multivariate binary and ordered
response models of walking and bicycling behavior. RESULTS: The motivators and
deterrents of active travel differed for walkers, bicyclists, and noncyclists
interested in bicycling. The link between active travel and life satisfaction was
moderated by age, with a negative association for older travelers. This effect
was stronger for bicycling than it was for walking. CONCLUSIONS: Based on the
findings, several interventions to encourage walking and bicycling were
suggested. These included infrastructure and built environment enhancements,
workplace programs, and interventions targeting specific subpopulations.
PMID- 28422548
TI - Epidemiological Profile and Treatment Outcomes in Young Adults (19-29 Years of
Age) Treated for Cancer in a Tertiary Hospital in Sao Paulo, Brazil.
AB - BACKGROUND: Worldwide, the incidence of cancer in young adults (20-39 years) is
increasing, and represents an important cause of mortality in this age group. A
retrospective study was undertaken to provide information that may lead to
improved treatment outcomes. METHODS: Epidemiological, clinicopathological,
treatment, and survival information were retrieved from the electronic database
registry of a tertiary referral hospital in Sao Paulo, Brazil for patients 19-29
years of age diagnosed with cancer between January 2007 and December 2012.
RESULTS: There were 960 patients with a median age at diagnosis of 26 years;
female patients comprised 59.2%. A previous diagnosis of malignancy was present
in 2.3%; 0.4% had malignant tumors that were radiation-associated; regular
alcohol use was present in 10.4%; 9% of patients reported tobacco use; a family
history of cancer was present in 41.7%. Malignant tumors included carcinomas
(45.7%), germ cell and trophoblastic neoplasms (12.3%), and lymphomas (12.1%).
Median follow-up was 47.7 months (range: 0.62-100.9 months) during which time 111
patients (13.5%) died. Carcinomas (n = 43, 38.7%), soft tissue sarcomas (n = 18,
16.2%), and leukemias (n = 10, 9.0%) were the most common causes of death.
CONCLUSIONS: This study has shown that carcinomas represent the most common
malignancy in adolescents and young adults referred to a tertiary cancer center
in Brazil and are the most common cause of mortality. Because clinical outcome
may be affected by multiple factors in this patient population, further global
studies are needed to characterize this population and improve clinical care.
PMID- 28422549
TI - Obesity is Associated With Altered Plantar Pressure Distribution in Older Women.
AB - Increased plantar pressure has been found to be related with greater risk of
falling. Although there is evidence suggesting that obesity is linked to foot
disorders, the association between obesity and plantar pressure of older adults
has been poorly investigated. The purpose of this study was to examine the
association between obesity and plantar pressure distribution and to explore its
relationship with body fat distribution. Two hundred and eleven older women took
part in this cross-sectional study. Body mass index was taken for obesity
classification. Whole body, android, and gynoid fat percentage was assessed using
dual-energy x-ray absorptiometry. Peak plantar pressure was evaluated during gait
using an Emed AT-4 pressure platform. Obese volunteers generated greater peak
pressure at midfoot (187.26 kPa) compared to both normal weight (128.52 kPa, p <
.001) and overweight (165.74 kPa, p < .001). Peak plantar pressure at midfoot was
also greater in overweight compared to normal weight (p < .001). At forefoot,
peak pressure was higher in the obese (498.15 kPa) compared to normal weight
volunteers (420.41 kPa, p = .007). Additionally, whole body, android, and gynoid
fat percentage were significantly associated with peak pressure at midfoot and
forefoot. Therefore, clinicians dealing with falls should consider the effect of
increased body weight on plantar pressure.
PMID- 28422550
TI - Evaluation of the diagnostic accuracy of UBC(r) Rapid in bladder cancer: a
Swedish multicentre study.
AB - OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of
UBC(r) Rapid - a urine-based marker for bladder cancer - in patients with bladder
cancer and controls, and to compare the test results across risk groups.
MATERIALS AND METHODS: This prospective phase II study was conducted at four
Swedish hospitals. UBC Rapid was evaluated in four groups: A, newly diagnosed
bladder cancer (n = 94); B, follow-up of non-muscle-invasive bladder cancer (n =
75); C, benign urinary tract diseases (n = 51); and D, healthy controls (n = 50).
Tumours were divided into high risk (carcinoma in situ, TaG3, T1, T2 and T3) and
low risk (low malignant potential, TaG1 and TaG2). Urine samples were
quantitatively analysed by UBC Rapid. Sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) were calculated based
on optimal cut-off (receiver operator characteristics curve analysis). A linear
regression compared the UBC Rapid results in the different risk groups. RESULTS:
The optimal cut-off was 8.1 MUg/l. The median UBC Rapid values were 9.3 MUg/l
[interquartile range (IQR) 30.9] and 4.3 MUg/l (IQR 7.8) in patients with
positive and negative cystoscopy, respectively (p < .001). The value for group A
was 15.6 MUg/l (IQR 37.9), group B 5.6 MUg/l (IQR 8.6), group C 5.1 MUg/l (IQR
9.0) and group D 3.3 MUg/l (IQR 7.1). Sensitivity was 70.8%, specificity 61.4%,
PPV 71.3% and NPV 60.8%. The high-risk group had significantly higher UBC Rapid
values than the low-risk group: 20.5 MUg/l (IQR 42.2), sensitivity 79.2% and
specificity 61.4% versus 7.0 MUg/l (IQR 9.9), sensitivity 60.0% and specificity
61.4% (p = .039). CONCLUSIONS: The UBC Rapid urine-based marker for bladder
cancer gave higher values in patients with positive than in those with negative
cystoscopy. The diagnostic accuracy was better in patients with high-risk than in
those with low-risk tumours, and was better during primary detection than during
surveillance.
PMID- 28422551
TI - Estimation of Gait Independence Using a Tri-Axial Accelerometer in Stroke
Patients.
AB - The purpose of this study was to clarify whether a gait analysis using an
accelerometer could estimate gait independence. Eighty-six stroke patients and 21
healthy control subjects participated in this study. Stroke patients were
identified as dependent or independent based on their gait ability. The
acceleration of the trunk and bilateral thigh was measured using three wireless
sensors during walking. The root mean square, gait regularity, and symmetry were
calculated from the acceleration to estimate gait quality. ANCOVA showed that
gait regularity of the trunk and bilateral thigh were significantly lowest in the
dependent group, regardless of gait velocity. A logistic regression analysis
showed that the regularity and root mean square of the anteroposterior
acceleration of the unaffected thigh were the key factors for estimating gait
independence. This study suggests that an acceleration-based gait analysis
facilities gait independence estimation, and is a useful tool during the
rehabilitation of stroke patients.
PMID- 28422552
TI - Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Gilan
Province, Iran.
AB - PURPOSE: To conduct an assessment of avoidable blindness and diabetic retinopathy
(DR) in Gilan, 2014. METHODS: A cross-sectional population-based survey was
performed on a representative sample of urban and rural individuals aged >=50
years of the province. Blindness was defined as presenting visual acuity (PVA)
<3/60 in the better eye. Moderate visual impairment (MVI) and severe visual
impairment (SVI) were defined as 6/60 <= PVA <6/18 and 3/60 <= PVA <6/60 in the
better eye, respectively. Diabetes mellitus (DM) was determined based on random
blood sugar (RBS) levels >=200 mg/dL or a previous diagnosis. We used the
Scottish grading system to grade DR. RESULTS: We invited 2975 individuals from 85
clusters. Age- and sex-adjusted prevalence and 95% confidence interval (CI) of
blindness, SVI, MVI, and DM in 2587 participants (response rate: 86.9%) were 1.5%
(95% CI: 1.1-2.0), 1.5% (95% CI: 0.9-2.0), 11.3% (95% CI: 9.9-12.7) and 21.4%
(95% CI: 19.2-23.7), respectively. The leading causes of blindness were cataract
(47.1%), age-related macular degeneration (14.7%) and DR (8.8%). Cataract surgery
(CS) coverage was 69.3%. The main challenges for CS were cost and unawareness.
The outcome of CS was good in 66.9% of operated eyes. Any DR and/or maculopathy
were observed in 25.3% (95% CI: 21.0-29.5) of subjects including 12.6% (95% CI:
9.7-15.6) sight-threatening DR. In previously known DM cases, 215 (41.7%) had
never undergone an eye examination for DR. CONCLUSION: The proportion of
avoidable blindness and DR is considerable in Gilan Province.
PMID- 28422554
TI - Reply to J. Stenman et al.
PMID- 28422553
TI - Psychometric Properties of the Brazilian Portuguese Version of the PARmed-X for
Pregnancy.
AB - BACKGROUND: The Physical Activity Readiness Medical Examination (PARmed-X) for
Pregnancy aims to facilitate the communication between the health care provider,
the fitness professional and the pregnant woman. The purpose of the current study
was to test the psychometric properties of the Brazilian Portuguese version of
the PARmed-X for Pregnancy. METHODS: Reliability and validity of psychometric
properties of the Brazilian Portuguese version of the PARmed-X for Pregnancy were
tested in 107 women recruited from the Hospital de Clinicas de Porto Alegre.
Participants completed the first page of the instrument twice with a minimal
interval of 1 week for test-retest reliability analysis. The absolute and
relative contraindications to exercise on page 2 of the document were completed
by the obstetrician. RESULTS: Results indicated good evidence of construct
validity. The isolated items in the PARmed-X document presented a large
heterogeneity in kappa coefficients ranging from very low estimates to perfect
estimates. The overall indication of prescription of physical activity,
nonetheless, presented a good kappa coefficient of 0.749. CONCLUSIONS: The
Brazilian Portuguese version of the PARmed-X for Pregnancy can be applied as a
valid tool for medical screening by health care providers to help inform safe
exercise prescription during pregnancy.
PMID- 28422555
TI - Improved Local Control by Extensive Surgery in High-Risk Neuroblastoma May Be
Dependent on Adjuvant Radiotherapy.
PMID- 28422556
TI - The Acute Effects of Breaking Up Seated Office Work With Standing or Light
Intensity Walking on Interstitial Glucose Concentration: A Randomized Crossover
Trial.
AB - BACKGROUND: The aim of this randomized, 3-period, 3-treatment crossover trial was
to examine the acute effects of regularly breaking up seated office work with
short bouts of standing or light-intensity walking on postprandial interstitial
glucose concentration. METHODS: Seventeen middle-aged office workers performed 3
5-hour trial conditions at their workplace in a random order: 1) uninterrupted
sitting, 2) sitting interrupted by 2 minutes of standing every 20 minutes, and 3)
sitting interrupted by 2 minutes of light-intensity walking every 20 minutes.
Participants consumed 2 standardized test drinks at the start of each trial
condition and an iPro2 continuous glucose monitoring system (CGMS) recorded
average interstitial glucose concentration every 5 minutes for the duration of
the study. RESULTS: The 5-hour interstitial glucose incremental area under the
curve (iAUC) was 55.5% lower after sitting interrupted by light-intensity walking
compared with after uninterrupted sitting (95% CI, -104.2% to -6.8%). There was
also a suggestion of a beneficial effect of regular standing breaks, particularly
in overweight men, although they were not as effective as the walking breaks
(mean difference [95% CI], -29.6% [-73.9% to 14.7%]). CONCLUSIONS: Regularly
breaking up prolonged sitting lowers postprandial glycemia in middle-aged adults
without metabolic impairment.
PMID- 28422557
TI - Maximal Aerobic Power in Aging Men: Insights From a Record of 1-Hour
Unaccompanied Cycling.
AB - PURPOSE: To analyze best 1-h unaccompanied performances of master athletes in
ages ranging from 35 to 105 y to estimate the decay of maximal aerobic power
(MAP) across the spectrum of age. METHODS: MAP at the various ages was estimated
by computing the metabolic power ([Formula: see text]) maintained to cover the
distances during best 1-h unaccompanied performances established by master
athletes of different classes of age and by assuming that they were able to
maintain an [Formula: see text] equal to 88% of their MAP during 1 h of
exhaustive exercise. RESULTS: MAP started monotonically decreasing at 47 y of
age. Thereafter, it showed an average rate of decrease of ~14% for the decades up
to 105 y of age, similar to other classes of master athletes. CONCLUSIONS: The
results confirm, by extending the analysis to centennial subjects, that MAP seems
to start declining from the middle of the 5th decade of age, with an average
percentage decay that is faster than that traditionally reported, even when one
maintains a very active lifestyle. The proposed approach may be applied to other
types of human locomotion for which the relationship between speed and [Formula:
see text] is known.
PMID- 28422558
TI - Understanding Transgender Men's Experiences with and Preferences for Cervical
Cancer Screening: A Rapid Assessment Survey.
AB - PURPOSE: Transgender men are less likely than cisgender women to receive cervical
cancer screening. The purpose of the current study was to understand experiences
with and preferences for cervical cancer screening among transgender men.
METHODS: Ninety-one transgender men ages 21-63 completed the survey. The survey
evaluated experiences with and preferences for screening, including opinions
regarding human papillomavirus (HPV) self-sampling as a primary cervical cancer
screening. RESULTS: Half (50.5%) of participants did not have Pap smear screening
within the past 3 years. The majority (57.1%) of participants preferred HPV self
sampling over provider-collected Pap smear screening. Participants who reported
discrimination were more likely to prefer HPV self-sampling (odds ratio = 3.29,
95% confidence interval 1.38-7.84, P = 0.007). CONCLUSION: Primary HPV testing
via HPV self-sampling may improve cervical cancer screening uptake among
transgender men. Future work should pilot this innovative cervical cancer
screening method within this population.
PMID- 28422559
TI - The Influence of Ambulatory Aid on Lower-Extremity Muscle Activation During Gait.
AB - CONTEXT: Foot and ankle injuries are common and often require a nonweight-bearing
period of immobilization for the involved leg. This nonweight-bearing period
usually results in muscle atrophy for the involved leg. There is a dearth of
objective data describing muscle activation for different ambulatory aids that
are used during the aforementioned nonweight-bearing period. OBJECTIVE: To
compare activation amplitudes for 4 leg muscles during (1) able-bodied gait and
(2) ambulation involving 3 different ambulatory aids that can be used during the
acute phase of foot and ankle injury care. DESIGN: Within-subject, repeated
measures. SETTING: University biomechanics laboratory. PARTICIPANTS: Sixteen able
bodied individuals (7 females and 9 males). INTERVENTION: Each participant
performed able-bodied gait and ambulation using 3 different ambulatory aids
(traditional axillary crutches, knee scooter, and a novel lower-leg prosthesis).
MAIN OUTCOME MEASURE: Muscle activation amplitude quantified via mean surface
electromyography amplitude throughout the stance phase of ambulation. RESULTS:
Numerous statistical differences (P < .05) existed for muscle activation
amplitude between the 4 observed muscles, 3 ambulatory aids, and able-bodied
gait. For the involved leg, comparing the 3 ambulatory aids: (1) knee scooter
ambulation resulted in the greatest vastus lateralis activation, (2) ambulation
using the novel prosthesis and traditional crutches resulted in greater biceps
femoris activation than knee scooter ambulation, and (3) ambulation using the
novel prosthesis resulted in the greatest gastrocnemius activation (P < .05).
Generally speaking, muscle activation amplitudes were most similar to able-bodied
gait when subjects were ambulating using the knee scooter or novel prosthesis.
CONCLUSIONS: Type of ambulatory aid influences muscle activation amplitude.
Traditional axillary crutches appear to be less likely to mitigate muscle atrophy
during the nonweighting, immobilization period that often follows foot or ankle
injuries. Researchers and clinicians should consider these results when
recommending ambulatory aids for foot or ankle injuries.
PMID- 28422560
TI - Effect of Physical Activity Intervention in Prediabetes: A Systematic Review With
Meta-analysis.
AB - BACKGROUND: Prediabetes is a strong risk factor for the development of Type2
Diabetes Mellitus (T2DM). Modification in lifestyle plays an important role to
avoid the prognosis of T2DM and its complications in future. The aim of our study
was to focus on the effectiveness of physical activity (PA) intervention program
on different outcome measures in individuals with prediabetes. The effort of the
present review was to contribute to the existing literature by strengthening the
evidence pointing toward the positive impact of physical activity in individuals
with prediabetes. METHODS: Studies have been identified through database like
PubMed, Scopus, and ProQuest. Randomized and nonrandomized controlled trials have
been included. Nineteen articles have been selected for the qualitative analysis
and 08 for meta-analysis. RESULTS: PA intervention showed a favorable effect on
improving oral glucose tolerance (Risk ratio [RR] -0.26, 95% CI -0.06 to 0.07)
and fasting blood sugar (RR -0.05, 95% CI -0.14 to 0.04). It also showed the
favorable effect on glycated hemoglobin (HbA1C), maximum oxygen uptake (VO2max),
and body composition. CONCLUSION: Present review suggests that the PA promotion
and participation can help to slow down the progression of disease in individuals
with prediabetes and thus reduces the morbidity and mortality associated with
T2DM.
PMID- 28422561
TI - Development and Feasibility of a Structured Goals of Care Communication Guide.
AB - BACKGROUND: Discussing goals of care and advance care planning is beneficial, yet
how to best integrate goals of care communication into clinical care remains
unclear. OBJECTIVE: To develop and determine the feasibility of a structured
goals of care communication guide for nurses and social workers.
DESIGN/SETTING/SUBJECTS: Developmental study with providers in an academic and
Veterans Affairs (VA) health system (n = 42) and subsequent pilot testing with
patients with chronic obstructive pulmonary disease or heart failure (n = 15) and
informal caregivers (n = 4) in a VA health system. During pilot testing, the
communication guide was administered, followed by semistructured, open-ended
questions about the content and process of communication. Changes to the guide
were made iteratively, and subsequent piloting occurred until no additional
changes emerged. MEASUREMENTS: Provider and patient feedback to the communication
guide. RESULTS: Iterative input resulted in the goals of care communication
guide. The guide included questions to elicit patient understanding of and
attitudes toward the future of illness, clarify values and goals, identify end-of
life preferences, and agree on a follow-up plan. Revisions to guide content and
phrasing continued during development and pilot testing. In pilot testing,
patients validated the importance of the topic; none said the goals of care
discussion should not be conducted. Patients and informal caregivers liked the
final guide length (~30 minutes), felt it flowed well, and was clear.
CONCLUSIONS: In this developmental and pilot study, a structured goals of care
communication guide was iteratively designed, implemented by nurses and social
workers, and was feasible based on administration time and acceptability by
patients and providers.
PMID- 28422562
TI - From Perception to Action: The Mediating Role of Parental Safety Concerns on
Adolescents' Physical Activity.
AB - BACKGROUND: Parental safety concerns have been recognized as a critical
determinant of adolescents' physical activity. However, it is still uncertain
what factors relate to parental safety concern, and how they, in turn, affect
adolescents' physical activity. This study explored the mediating relationships
of parental safety concern on adolescents' physical activity by considering
personal, social, and built environmental factors. METHODS: This cross-sectional
analysis used the data from Growing Up in Ireland (GUI), a national study (N =
5212). A structural equation model (SEM) was used to evaluate the hypothesized
framework. RESULTS: 50% of the adolescents engaged in at least 6 days of exercise
every 14 days, at a rate of at least 20-minutes per day. Adolescents were more
physically active when parents perceived higher levels of safety. Parents
perceived their children as safe when they lived in areas with easy access to
play spaces. Moreover, adolescents with more close friends and more friends with
whom they could play were more physically active and their parents perceived
higher levels of safety. CONCLUSIONS: Parental safety concerns may profoundly
affect adolescent's physical activity and the resulting health outcomes. Programs
and policies should consider the importance of parental safety concerns in
promoting adolescents' physical activity.
PMID- 28422563
TI - Effects of Anterior Knee Displacement During Squatting on Patellofemoral Joint
Stress.
AB - CONTEXT: Squatting is a common rehabilitation training exercise for
patellofemoral pain syndrome (PFPS). Patellofemoral joint stress (PFJS) during
squatting with more anterior knee displacement has not been systematically
investigated. OBJECTIVE: To compare PFJS during squatting using 2 techniques:
squat while keeping the knees behind the toes (SBT) and squat while allowing the
knees to go past the toes (SPT). SETTING: University research laboratory.
PARTICIPANTS: Twenty-five healthy females (age: 22.69 (0.74) y; height: 169.39
(6.44) cm; mass: 61.55 (9.74) kg) participated. MAIN OUTCOME MEASURES: Three
dimensional kinematic and kinetic data were collected at 180 and 1800 Hz,
respectively. A musculoskeletal model was used to calculate muscle forces through
static optimization. These muscle forces were used in a patellofemoral joint
model to estimate PFJS. RESULTS: The magnitudes of PFJS, reaction force, and
quadriceps force were higher (P < .001) during SPT compared with the SBT
technique. Knee flexion, hip flexion, and ankle dorsiflexion angles were reduced
when using the SBT technique. CONCLUSIONS: Findings provide some general support
for minimizing forward knee translation during squats for patients that may have
patellofemoral pain syndrome.
PMID- 28422564
TI - Evaluation of two in-house immunoenzymatic tests to serodiagnose subclinical
paratuberculisis in a sheep flock in Mexicali valley, Mexico.
AB - Paratuberculosis (PTB) or Johne's disease is a common ruminant infectious disease
caused by Mycobacterium avium subsp. paratuberculosis (MAP). In this study, two
MAP antigens were compared for their diagnostic utility to detect subclinical PTB
in a sheep flock in Mexicali, Mexico. Sheep (n = 31) without clinical signs but
positive on a direct fecal-polymerase chain reaction were tested with two
preabsorbed in-house enzyme linked immunosorbent assays (ELISAs) using: (1) an
ethanol-extracted surface lipid antigen (EVELISA) and (2) a protoplasmic antigen
(ELISA-PPA). Sensitivities of the EVELISA and ELISA-PPA were 84% (95% CI; 66-95%)
and 29% (95% CI; 14-48%), respectively. The EVELISA test could be a fast and
effective way to identify subclinical ovine PTB for severely affected flocks.
PMID- 28422565
TI - Ascorbic acid deficiency in patients with lichen planus.
AB - OBJECTIVES: Recent studies have highlighted the role of oxidative stress in the
pathogenesis of lichen planus (LP). In the present study, the interest of the
authors is focused on the investigation of ascorbic acid status in patients with
LP and identification of parameters that might influence the level of this
vitamin. MATERIAL AND METHOD: We analyzed the level of urinary ascorbic acid
(reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral
LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants
included clinical examination and laboratory and imaging tests. RESULTS: Compared
to the control group (19.82 mg/dl) the level of ascorbic acid was significantly
lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP
(8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of
ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary
concentrations of ascorbic acid were significantly lower in patients with LP
associated with infections compared to patients with LP without infections.
CONCLUSIONS: The urinary ascorbic acid level may be a useful parameter in
identifying patients with LP who are at risk of developing viral or bacterial
infections.
PMID- 28422566
TI - Content uniformity testing for stratified samples via parametric tolerance
interval testing.
AB - Historically in the biopharmaceutical setting, USP<905> has been used to
establish that a batch of drug product has acceptable content uniformity. More
recently, alternative approaches such as the two one-sided parametric tolerance
interval test (PTI-TOST) have been proposed to establish content uniformity.
Traditionally, the PTI-TOST is implemented as a sequential, two-tiered test,
under the generally accepted assumption that the data are independently and
identically distributed. Since the material is sequenced through the
manufacturing process over a period of time, there are conceptually arguable
locations within each batch, for instance: beginning, middle, and end. In such a
situation, a practitioner may wish to evaluate potential effects of these batch
locations, for example, during process validation. If location (stratified)
differences exist within the batch and if multiple samples are taken from each
location, significant within-location correlations may be induced in the data. In
such a case, the traditional PTI-TOST underestimates the total variability,
thereby improperly boosting the power of the test method. When there is reason to
believe that location variances exist, the batch may be evaluated using
stratified sampling, and the location effect may be modeled. In this paper, a two
tiered PTI-TOST that accounts for both between-location and within-location
variance components is introduced. Operating characteristic curves and practical
advice are given to aid the practitioner's uptake of the proposed method.
PMID- 28422567
TI - Evaluation of serotypes 5 and 8 capsular polysaccharides in protection against
Staphylococcus aureus in murine models of infection.
AB - Staphylococcus aureus is the leading cause of nosocomial and community-acquired
infections, including soft tissue and skin infections and bacteremia. However,
efforts to develop an effective vaccine against S. aureus infections have not
been successful. We evaluated serotypes 5 and 8 capsule polysaccharides (CP)
CRM197 conjugates as vaccine candidates in murine models of bacteremia, lethal
sepsis, and skin infection. The conjugate vaccines elicited a good antibody
response, and active immunization of CP5-CRM or CP8-CRM conjugates protected
against staphylococcal bacteremia. In the skin infection model, CP8-CRM but not
CP5-CRM protected against dermonecrosis, and CP8-CRM immunization significantly
decreased the bacterial burden in the lesion. However, neither CP5-CRM nor CP8
CRM protected against mortality in the lethal sepsis model. The results indicate
the capsular vaccines elicit protection against some, but not all, aspects of
staphylococcal infection.
PMID- 28422569
TI - Preparation of a novel antibacterial chitosan-poly(ethylene glycol)
cryogel/silver nanoparticles composites.
AB - Cryogel was synthesized through cryogelation of methacrylated carboxymethyl
chitosan (mCMC) and poly(ethylene glycol) diacrylate (PEGDA) precursors by
photopolymerization. Due to its excellent properties, such as fast swelling
behavior, inter-connective porous structure, high water absorbing capacity,
especially the presence of abundant carboxylmethyl groups on its backbone, the
cryogel not only favored the absorption of silver ions but also was proved to be
a good matrix for the incorporation of silver nanoparticles (AgNPs) by in situ
chemical reduction. The structure, morphology, and swelling behavior of the
cryogel and cryogel/AgNPs composite were characterized. And the results of
inhibition zone test and antibacterial inhibition ratio indicated the
cryogel/AgNPs composite exhibited prominent and durable antibacterial activity
against Gram-negative E. coli and could be utilized as potential antibacterial
materials.
PMID- 28422568
TI - cGAS-STING-TBK1-IRF3/7 induced interferon-beta contributes to the clearing of non
tuberculous mycobacterial infection in mice.
AB - Type I interferons (IFN-I), such as IFN-alpha and IFN-beta are important
messengers in the host response against bacterial infections. Knowledge about the
role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here
we show that macrophages infected with pathogens of the Mycobacterium avium
complex produced significantly lower amounts of IFN-beta than macrophages
infected with the opportunistic pathogen M. smegmatis. To dissect the molecular
mechanisms of this phenomenon, we focused on the obligate pathogen Mycobacterium
avium ssp paratuberculosis (MAP) and the opportunistic M. smegmatis. Viability of
both bacteria was required for induction of IFN-beta in macrophages. Both
bacteria induced IFN-beta via the cGAS-STING-TBK1-IRF3/7-pathway of IFN-beta
activation. Stronger phosphorylation of TBK1 and higher amounts of extracellular
bacterial DNA in the macrophage cytosol were found in M. smegmatis infected
macrophages than in MAP infected macrophages. After intraperitoneal infection of
mice, a strong Ifnb induction by M. smegmatis correlated with clearance of the
bacteria. In contrast, MAP only induced weak Ifnb expression which correlated
with bacterial persistence and increased number of granulomas in the liver. In
mice lacking the type I interferon receptor we observed improved survival of M.
smegmatis while survival of MAP was similar to that in wildtype mice. On the
other hand, treatment of MAP infected wildtype mice with the IFN-I inducer
poly(I:C) or recombinant IFN-beta impaired the survival of MAP. This indicates an
essential role of IFN-I in clearing infections by MAP and M. smegmatis. The
expression level of IFN-I is decisive for transient versus persistent NTM
infection.
PMID- 28422570
TI - An Induced Adipocyte Sheet Reduces Inflammatory Reactions During Remodeling of
Xenogeneic Scaffolds In Vivo.
AB - Surgical therapy of cardiovascular diseases frequently requires replacement of
diseased tissues with prosthetic devices or grafts. Calcification is the main
reason for the degeneration of implanted grafts. However, some factors reduce
stenosis and attenuate calcification of implanted grafts. In this study, we used
an autologous induced adipocyte cell-sheet (IACS) as a drug delivery system to
determine whether its secretion ability has a beneficial effect on the remodeling
process of grafts in a rat subcutaneous model. IACSs were generated from rat
adipose tissue-derived cells that secreted abundant adiponectin (APN), hepatocyte
growth factor, and vascular endothelial growth factor in vitro. Two types of
grafts were used in the rat subcutaneous model: decellularized and IACS-wrapped
decellularized porcine vascular grafts. Transplanted IACSs secreted APN into the
decellularized porcine vascular graft in rats at 4 weeks. After explanting from
the rat subcutaneous model at 1, 2, 4, and 8 weeks, immunofluorescence staining
showed that IACS-wrapped grafts had a dominant M2 phenotype of macrophages (p <
0.001) at all time points and showed constructive remodeling and less
calcification at 8 weeks. The decellularized graft showed a predominately CCR7+
cell response (M1 phenotype) (p < 0.001) and was characterized by chronic
inflammation and severe calcification at 8 weeks. Furthermore, the IACS-wrapped
side of the graft showed less cell infiltration compared with the other side,
which may have reduced inflammation in the area. Transplantation of IACSs with a
biological scaffold had a profound influence on the macrophage phenotype and
downstream remodeling processes. The method might reduce inflammatory reactions
during remodeling of xenogeneic scaffolds and result in less calcification.
PMID- 28422571
TI - Reliability of Measuring Lower-Limb-Muscle Electromyography Activity Ratio in
Activities of Daily Living With Electrodes Embedded in the Clothing.
AB - CONTEXT: Using technical clothes with electrodes embedded in the clothing makes
it possible to record the electrical activity produced by the activity of the
skeletal muscles in activities of daily living. OBJECTIVE: To investigate the
reliability of measuring lower-limb left-right electromyography (EMG) activity
ratio with smart shorts during stair descent, stair ascent, and repeated unloaded
squats among healthy working-aged subjects. METHODS: Seventeen females (mean age
25.5 y), and 17 males (mean age 29.9 y) participated in this test-retest protocol
carried out twice on the same day. RESULTS: Intraclass correlation coefficient
(ICC) varied from .65 to .80 in the different activities. Mean difference and
limits of agreement (LOA) between the repeated measurements were for descending
stairs -0.8%, LOA -6.2% to 4.7%; for ascending stairs -0.9%, -6.5% to 4.7%; and
for squats -0.2%, -5.4% to 4.9%. The coefficient of repeatability for descending
stairs was 5.6%, for ascending stairs 5.7%, and for squats 5.3%. CONCLUSIONS: Our
study among healthy subjects showed that the left-right EMG activity ratio in
activities of daily living can be reliably measured with smart shorts. In future
research, the feasibility of technical clothes as a follow-up method in
rehabilitation should be investigated in greater detail.
PMID- 28422572
TI - Effect of Comprehensive School Physical Activity Programming on Cardiometabolic
Health Markers in Children From Low-Income Schools.
AB - BACKGROUND: The purpose of this study was to examine the effect of a 36-week
Comprehensive School Physical Activity Program (CSPAP) on cardiometabolic health
markers in children from low-income schools. METHODS: Participants were 217
school-aged children (mean age = 10.1 +/- 1.1 years; 114 girls, 103 boys)
recruited from 5 low-income elementary schools. Cardiometabolic health markers
were collected in a fasted state at 2 time-points, before commencement of the
CSPAP for classroom and school level clustering and the modifying effects of
grade level and sex, there were statistically significant improvements in HDL
cholesterol (Delta = 3.6 mg/dL, 95% CI: 1.4 mg/dL to 5.8 mg/dL, P = .039),
triglycerides (Delta = -14.1 mg/dL, 95% CI: -21.4 mg/dL to -6.8 mg/dL, P = .022),
and mean arterial pressure (Delta = -4.3 mmHg, 95% CI: -8.5 mmHg to -0.1 mmHg, P
= .041) following the 36-week CSPAP intervention. Sixth-grade children showed
decreases in LDL cholesterol (Delta = -15.3 mg/dL, 95% CI: -30.5 mg/dL to -0.1
mg/dL, P = .033). CONCLUSIONS: Improvements in specific cardiometabolic health
markers were found following a 36-week CSPAP in children from low-income schools.
PMID- 28422573
TI - Results From the First French Report Card on Physical Activity for Children and
Adolescents.
AB - BACKGROUND: Many countries publish periodic Report Cards on physical activity for
children and youth. This paper presents the results from the first French Report
Card providing a systematic synthesis and assessment of the national engagements
to facilitate childhood physical activity. METHODS: A search for nationally
representative data on 8 indicators of physical activity was conducted and the
data were assessed by an expert panel according to international procedures.
Whether children across France are achieving specific benchmarks was rated using
an established grading framework [A, B, C, D, F, or INC (incomplete)]. Data were
interpreted, grades assigned and detailed in the 2016 Report Card that was
produced and disseminated. RESULTS: The expert panel awarded the following
grades: Overall Physical Activity: INC; Organized Sport Participation: D; Active
Transportation: D; Sedentary Behaviors: D; Family and Peers: INC; School: B;
Community and the Built Environment: INC; Government Strategies and Investment:
INC. CONCLUSIONS: The grades reveal that efforts must be done to improve youth's
physical activity and that several gaps in the literature still need to be
addressed. Collectively the results highlight that children's physical activity
levels are low and that further national supports and investments are needed to
promote childhood healthy active living in France.
PMID- 28422574
TI - Social-Cognitive and Social-Behavioral Correlates of Suicide Risk in College
Students: Contributions from Interpersonal Theories of Suicide and Depression.
AB - Joiner's interpersonal-psychological theory of suicide (IPTS) is predated by
literature examining maladaptive interpersonal behaviors associated with
depression; however, research has not examined the potential relevance of such
behaviors for the IPTS. The current study aimed to expand understanding of
suicide risk by examining two maladaptive interpersonal behaviors in the context
of Joiner's IPTS model. Structural equation modeling examined associations
between depressive symptoms, social-cognitive predictors of suicide, maladaptive
interpersonal behaviors, and suicide risk in 228 college students (53.9% female;
M = 19.5 years, SD = 1.8). Social-cognitive IPTS variables mediated the relation
between depressive symptoms and maladaptive interpersonal behavior. Both social
cognition and maladaptive interpersonal behavior mediated the effect of
depressive symptoms on suicide risk. Findings have the potential to add to our
understanding of the interplay of social-cognitive factors and interpersonal
behaviors associated with suicide risk. Directions for future research are
discussed.
PMID- 28422575
TI - Cardiovascular Risk Factors of Long-Term Care Workers.
AB - Little is known about long-term care workers' cardiovascular disease (CVD) risk.
Thus, the authors used baseline objective and subjective data from 98 long-term
care staff participating in a worksite health promotion study to provide a
comprehensive CVD assessment. The median age of the sample was 32 years ( SD =
13.38). Nine (12.2%) participants smoked and 27 (37.0%) participants reported
exposure to secondhand smoke. The average nightly hours of sleep was 6.5 ( SD =
1.18), with 24 (32%) participants reporting sleeping at least fairly bad. Sixty
eight participants (73.1%) were overweight or obese. The median aerobic activity
was 0 ( SD = 18.56). Participants ate on average 27 ( SD = 17.34) servings of
high fatty and/or salty foods per week. Although blood pressure and cholesterol
levels were within normal limits, this population demonstrated poor behavioral
CVD risk factors. Given this finding and the young age of the sample, these
workers may be ideal candidates for health promotion efforts before health risk
factors are present.
PMID- 28422576
TI - Mechanisms of Action Contributing to Reductions in Suicide Attempts Following
Brief Cognitive Behavioral Therapy for Military Personnel: A Test of the
Interpersonal-Psychological Theory of Suicide.
AB - Brief cognitive behavioral therapy (BCBT) is associated with significant
reductions in suicide attempts among military personnel. However, the underlying
mechanisms of action contributing to reductions in suicide attempts in effective
psychological treatments remain largely unknown. The present study conducted a
secondary analysis of a randomized controlled trial of BCBT versus treatment as
usual (TAU) to examine the mechanisms of action hypothesized by the interpersonal
psychological theory of suicide (IPT): perceived burdensomeness, thwarted
belongingness, and fearlessness about death. In a sample of 152 active duty U.S.
Army personnel with recent suicide ideation or attempts, there were significantly
fewer suicide attempts in BCBT, but there were no differences between treatment
groups from baseline to 6 months postbaseline on any of the 3 IPT constructs or
their interactions. Tests of the moderated mediation failed to support an
indirect effect for the IPT model, regardless of which IPT variables were
specified as mediators or moderators. Results suggest that the IPT's hypothesized
mechanisms of action do not account for reductions in suicide attempts in BCBT.
Implications for clinical practice and research are discussed.
PMID- 28422577
TI - Enrichment of Zebrafish Danio rerio (Hamilton, 1822) Diet with Polyunsaturated
Fatty Acids Improves Fecundity and Larvae Quality.
AB - The zebrafish is a freshwater fish of the Cyprinidae family, which is frequently
used in scientific research. It owes its popularity to its genome, whose
structure is comparable to the human genome and, for this reason, this species is
often used in human medical research. However, such research requires high
quality material to conduct tests producing repeatable results. This study
examines the effect of providing feed enriched with essential fatty acids,
especially docosahexaenoic acid, to zebrafish spawners on fertility as well as
the survival rate and growth of their offspring. The experiments revealed a
significant (p < 0.05) effect of feeding spawners with feed enriched with
polyunsaturated fatty acids on all tested parameters: their fertility (30% higher
compared to the control group), survival rate, and the posthatching size of
larvae, which were larger by 13% and 4%, respectively, compared to the control
group.
PMID- 28422578
TI - Korean Version of the Mini-Mental State Examination Using Smartphone: A
Validation Study.
AB - BACKGROUND: Stroke often leads to disability, and poststroke survivors often have
limited accessibility to medical facilities. INTRODUCTION: For such patients,
mobile videoconferencing technology offers an opportunity to perform follow-up
assessment and appropriate management of cognitive impairment. We aimed to
determine the validity of the Korean version of the Mini-Mental State Examination
(MMSE-K) when administered using a smartphone. MATERIALS AND METHODS: Thirty
patients with ischemic or hemorrhagic stroke were included in this study (20
males, 10 females; mean age, 69.8 +/- 12.9 years). Both face-to-face and remote
assessments of cognitive function through MMSE-K were performed for each patient
at an interval of at least 3 days. Additionally, an in-person collaborator
evaluated the MMSE-K score during the remote assessment. A smartphone and a
tablet were used by the patient and the examiner, respectively, and remote
connection was mediated using a dedicated videoconferencing application. The MMSE
K scores obtained through face-to-face, remote, and in-person assessments were
compared using the Wilcoxon signed rank test and the Spearman correlation
analysis. RESULTS: There was good agreement between face-to-face and remote
assessments, as well as between remote assessment and in-person collaborator's
evaluation regarding total MMSE-K score and subscores for each MMSE-K domain
(orientation, memory, attention/calculation, language, and visuospatial
function). DISCUSSION: Remote assessment can be a useful clinical evaluation
method, and this study confirmed the validity. CONCLUSIONS: The smartphone
represents a promising tool for the assessment of cognitive function in clinical
practice, but further research into the intra- and inter-rater reliability of
observations is warranted.
PMID- 28422579
TI - Is the Higher Number of Suicide Attempts in Bipolar Disorder vs. Major Depressive
Disorder Attributable to Illness Severity?
AB - The present study represents an early stage investigation into the phenomenon
whereby those with bipolar disorder attempt suicide more frequently than those
with unipolar depression, but do not tend to attempt suicide during mania. Data
for this study were obtained from baseline measurements collected in a randomized
treatment study at a major southwestern United States military medical center. We
demonstrated the rarity of suicide attempts during mania, the higher frequency of
suicide attempts in those with bipolar disorder compared to those with
depression, and the persistence of effects after accounting for severity of
illness. These results provide the impetus for the development and testing of
theoretical explanations.
PMID- 28422580
TI - Glyphosate and Paraquat in Maternal and Fetal Serums in Thai Women.
AB - OBJECTIVES: This longitudinal study measured the glyphosate and paraquat
concentrations found in maternal and umbilical cord serum in 82 pregnant women
who gave birth in three provinces of Thailand. METHODS: Through questionnaires
and biological samples collected at childbirth, factors such as personal
characteristics, family members occupation, agricultural activities, and
herbicide use in agricultural work were evaluated as predictors of glyphosate and
paraquat levels in the pregnant women. Statistical analysis used univariate and
binary multiple logistic regression, where the outcome was the probability of
exposure to paraquat or glyphosate above the limit of detection associated with
occupation and household factors. RESULTS: The glyphosate concentrations in the
pregnant women's serum at childbirth (median: 17.5, range: 0.2-189.1 ng/mL) were
significantly higher (P < .007) than those in the umbilical cord serum (median:
0.2, range: 0.2-94.9 ng/mL). However, the paraquat concentrations in the serum of
the pregnant women at childbirth (83% <=limit of detection [LOD], with maximum of
58.3 ng/mL) were similar to those in the umbilical cord serum (80% LOD in serum at childbirth
were 11.9 times more likely to report work as an agriculturist (P < .001), 3.7
times more likely to live near agricultural areas (P = .006), and 5.9 times more
likely to have a family member who worked in agriculture (P < .001). The only
factors affecting paraquat exposures in pregnant women at childbirth were
reporting the agricultural activity of digging in farm soil and working in the
agricultural fields in the third trimester of pregnancy. CONCLUSIONS: These
results show that pregnant women who work in agriculture or live in families that
work in agriculture have higher exposures to the herbicides glyphosate and
paraquat. The potential for long-term health impacts of these prenatal exposures
to children should be evaluated, and greater regulation of the sale and use of
herbicides should be considered in Thailand.
PMID- 28422581
TI - "Straight from the heavens into your bucket": domestic rainwater harvesting as a
measure to improve water security in a subarctic indigenous community.
AB - BACKGROUND: Black Tickle-Domino is an extremely water-insecure remote Inuit
community in the Canadian subarctic that lacks piped-water. Drinking water
consumption in the community is less than a third of the Canadian national
average. Water insecurity in the community contributes to adverse health,
economic, and social effects and requires urgent action. OBJECTIVES: To test the
ability of domestic rainwater harvesting (DRWH) for the first time in the
subarctic with the goal of improving water access and use in the community.
DESIGN: This project utilised quantitative weekly reporting of water collection
and use, as well as focus group discussions. DRWH units were installed at seven
water-insecure households chosen by the local government. Results were measured
over a 6-week period in 2016. RESULTS: Participants harvested 19.07 gallons of
rainwater per week. General purpose water consumption increased by 17% and water
retrieval efforts declined by 40.92%. Households saved $12.70 CDN per week.
Participants reported perceived improvements to psychological health. Because no
potable water was collected, drinking water consumption did not increase. The
study identified additional water-insecurity impacts. CONCLUSION: DRWH cannot
supply drinking water without proper treatment and filtration; however, it can be
a partial remedy to water insecurity in the subarctic. DRWH is appropriately
scaled, inexpensive, and participants identified several significant benefits.
PMID- 28422582
TI - Combining Activity-Related Behaviors and Attributes Improves Prediction of Health
Status in NHANES.
AB - BACKGROUND: This paper tested whether a physical activity index (PAI) that
integrates PA-related behaviors (ie, moderate-to-vigorous physical activity
[MVPA] and TV viewing) and performance measures (ie, cardiorespiratory fitness
and muscle strength) improves prediction of health status. METHODS: Participants
were a nationally representative sample of US adults from 2011 to 2012 NHANES.
Dependent variables (self-reported health status, multimorbidity, functional
limitations, and metabolic syndrome) were dichotomized. Wald-F tests tested
whether the model with all PAI components had statistically significantly higher
area under the curve (AUC) values than the models with behavior or performance
scores alone, adjusting for covariates and complex survey design. RESULTS: The
AUC (95% CI) for PAI in relation to health status was 0.72 (0.68, 0.76), and PAI
AUC for multimorbidity was 0.72 (0.69, 0.75), which were significantly higher
than the behavior or performance scores alone. For functional limitations, the
PAI AUC was 0.71 (0.67, 0.74), significantly higher than performance, but not
behavior scores, while the PAI AUC for metabolic syndrome was 0.69 (0.66, 0.73),
higher than behavior but not performance scores. CONCLUSIONS: These results
provide empirical support that an integrated PAI may improve prediction of health
and disease. Future research should examine the clinical utility of a PAI and
verify these findings in prospective studies.
PMID- 28422583
TI - Altering the Speed Profiles of Wheelchair Rugby Players With Game-Simulation
Drill Design.
AB - PURPOSE: To examine the speed profiles of elite wheelchair rugby (WCR) players
during game-simulation training drills of differing player number and shot-clock
regulations. A secondary aim was to determine whether the profiles were further
influenced by player classification. METHODS: Eight elite WCR players (low-point
n = 3, high-point n = 5) were monitored using a radio-frequency-based indoor
tracking system during training sessions over a 5-mo period. Speed profiles were
collected for 3 modified game-simulation drills-3-versus-3 drills (n = 8
observations), 30-s shot clock (n = 24 observations), and 15-s shot clock (n = 16
observations)-and were compared with regular game-simulation drills (4 vs 4, 40-s
shot clock; n = 16 observations). Measures included mean and peak speed; exercise
intensity ratios, defined as the ratio of time spent performing at high and low
speeds; and the number of high-speed activities performed. RESULTS: Compared with
regular game-simulation drills, 3-versus-3 drills elicited a moderate increase in
mean speed (6.3%; effect size [ES] = 0.7) and the number of high-speed activities
performed (44.1%; ES = 1.1). Minimal changes in speed profiles were observed
during the 30-s shot clock, although moderate to large increases in all measures
were observed during the 15-s shot-clock drills. Classification-specific
differences were further identified, with increased activity observed for high
point players during the 3-versus-3 drill and for low-point players during the 15
s shot clock. CONCLUSION: By reducing the number of players on court and the shot
clock to 15 s, coaches can significantly increase elite WCR players' speed
profiles during game-simulation drills.
PMID- 28422584
TI - Pre- and post-prostatectomy variables associated with pelvic post-operative
radiotherapy in prostate cancer patients: a national registry-based study.
AB - BACKGROUND: In patients with prostate cancer (PCa), the lack of clear guidelines
on the use of radiotherapy after radical prostatectomy (RP) invites unwanted
variation of this treatment. We describe the hazard ratios and probabilities
related to the use of post-RP radiotherapy. MATERIAL AND METHODS: Data were
collected from the Cancer Registry of Norway and nine radiotherapy units. All
patients were diagnosed with a non-metastatic PCa from January 2004 through June
2011. Adjuvant radiotherapy was defined as pelvic radiotherapy initiated <5
months after RP at a PSA <0.2 ng/ml. All other pelvic radiotherapy series were
categorized as salvage radiotherapy, and, combined with adjuvant radiotherapy
they were termed post-RP radiotherapy. RESULTS: Of 6840 prostatectomized
patients, 1170 (17%) had undergone post-RP radiotherapy, mainly as salvage
radiotherapy. The number of adjuvant radiotherapy series almost tripled from
2009. Based on pre-prostatectomy variables (PSA, Gleason score, and clinical risk
group) and findings in the prostatectomy specimens (status of resection margins,
pathological tumor category and Gleason's score), the probability of post-RP
radiotherapy ranged respectively from 14% to 73%, and from 4% to 83%.
CONCLUSIONS: In our study, post-RP radiotherapy was applied in approximately one
in six patients. Based on the combination of PCa-specific variables routinely
available at the time of diagnosis, a patient's probability of post-RP
radiotherapy can be determined before decision of primary treatment strategy,
followed by probability determination based on histopathological variables
emerging from the prostatectomy specimen.
PMID- 28422585
TI - Validation of the IPAQ Against Different Accelerometer Cut-Points in Older Cancer
Survivors and Adults at Risk of Cancer.
AB - The present study investigated the convergent validity of an interview
administered IPAQ long version (IPAQ-L) in an older population by comparison with
objective accelerometry movement data. Data from 52 participants (mean age 67.9
years, 62% male) were included in the analysis. Treadmill derived (TM-ACC: 1,952
5,724 cpm) and free-living physical activity (PA) derived (FL-ACC: 760-5,724 cpm)
accelerometer cut-points were used as criterion. IPAQ-L measures (total PA,
leisure-time, walking-time, sedentary time) were significantly correlated with
accelerometry (P <= .05). Differences in sex were observed. Bland-Altman Limits
of Agreement analysis showed that the IPAQ-L overestimated PA in relation to
accelerometry. Our results show that an interview-administered IPAQ-L shows low
to moderate convergent validity with objective PA measures in this population but
there may be differences between males and females which should be further
investigated.
PMID- 28422586
TI - Biomechanical Determinants of the Reactive Strength Index During Drop Jumps.
AB - The Reactive Strength Index (RSI) is often used to quantify drop-jump (DJ)
performance; however, not much is known about its biomechanical determinants. The
purpose of this study was to investigate the correlations between the RSI and
several biomechanical variables calculated from DJ performed with different
initial drop heights. Twelve male NCAA Division I basketball players performed
DJs from drop heights of 30, 45, and 60 cm. Force plates were used to calculate
DJ performance parameters (ie, DJ height, contact time, and RSI) and DJ
biomechanical variables (ie, vertical stiffness and eccentric/concentric
energetics). Regression analyses were used to assess the correlations between
variables at each drop height, and ANOVAs were used to assess the differences of
all variables across drop heights. Follow-up analyses used 2 neural networks to
determine if DJ performance and biomechanical data could accurately classify DJ
trials by drop-height condition. Vertical-stiffness values were significantly
correlated with RSI at each height but did not change across drop heights.
Surprisingly, the RSI and other DJ parameters also did not vary across drop
height, which resulted in the inability of these variables to accurately classify
DJ trials. Given that vertical stiffness did not change across drop height and
was highly correlated with RSI at each height, the RSI appears to reflect
biomechanical behavior related to vertical stiffness during DJ. However, the
inability of the RSI to accurately classify drop-height condition questions the
use of RSI profiles established from DJs from different heights.
PMID- 28422587
TI - Comparing Campers' Physical Activity Levels Between Sport Education And
Traditional Instruction in a Residential Summer Camp.
AB - BACKGROUND: To date, studies examining physical activity (PA) levels have largely
been dedicated to the school setting, while there is little known about the
activity levels of children who participate in traditional or summer day camps.
METHODS: Participants were 83 11- to 12-year-old campers who partook in either
Sport Education or traditional instruction at a large residential summer camp.
All lessons were video recorded and coded using the System for Observing Fitness
Instruction Time (SOFIT), which categorizes PA levels as well as contextual
characteristics. RESULTS: Results indicated that campers who participated in
Sport Education spent a higher percentage of time (61.6%) engaged in moderate to
vigorous activity than campers in the traditional activity unit (42.2%). In
addition, campers spent less time idly within Sport Education (27.9%), than its
counterpart (39.5%). CONCLUSIONS: These findings indicate that utilizing the
Sport Education model may provide campers with higher levels of PA within this
context.
PMID- 28422588
TI - Alterations in Redox Homeostasis During Recovery From Unexplained
Underperformance Syndrome in an Elite International Rower.
AB - PURPOSE: To examine a diagnosis of unexplained underperformance syndrome (UUPS,
or overtraining syndrome) in an international rower describing a full recovery
and return to elite competition the same year. METHODS: On diagnosis and 4 and 14
mo postdiagnosis, detailed assessments including physiological, nutritional, and
biomarkers were made. RESULTS: Clinical examination and laboratory results for
hematology, biochemistry, thyroid function, immunology, vitamins, and minerals
were unremarkable and did not explain the presentation and diagnosis. Redox
biomarkers including hydroperoxides, plasma antioxidant capacity, red blood cell
glutathione, superoxide dismutase, coenzyme Q10, vitamin E (alpha- and gamma
tocopherol), and carotenoids (lutein, alpha-carotene, beta-carotene) provided
evidence of altered redox homeostasis. The recovery strategy began with 12 d of
training abstinence and nutritional interventions, followed by 6 wk of modified
training. At 4 mo postintervention, performance had recovered strongly, resulting
in the athlete's becoming European champion that same year. Further improvements
in physiological and performance indices were observed at 14 mo postintervention.
Physiologically relevant increases in concentrations of carotenoids were achieved
at each postintervention time point, exceeding the reported critical-difference
values. CONCLUSIONS: Increasing athlete phytonutrient intake may enhance recovery
and tolerance of training and environmental stressors, reducing the risk of
unexplained UUPS. Alterations in redox homeostasis should be considered as part
of the medical management in UUPS. This is the first reported case study of an
elite athlete with alterations in redox homeostasis in conjunction with a
diagnosis of UUPS.
PMID- 28422589
TI - Energy Expenditure in Vinyasa Yoga Versus Walking.
AB - BACKGROUND: Whether the energy cost of vinyasa yoga meets the criteria for
moderate-to-vigorous physical activity has not been established. PURPOSE: To
compare energy expenditure during acute bouts of vinyasa yoga and 2 walking
protocols. METHODS: Participants (20 males, 18 females) performed 60-minute
sessions of vinyasa yoga (YOGA), treadmill walking at a self-selected brisk pace
(SELF), and treadmill walking at a pace that matched the heart rate of the YOGA
session (HR-Match). Energy expenditure was assessed via indirect calorimetry.
RESULTS: Energy expenditure was significantly lower in YOGA compared with HR
Match (difference = 79.5 +/- 44.3 kcal; P < .001) and SELF (difference = 51.7 +/-
62.6 kcal; P < .001), but not in SELF compared with HR-Match (difference = 27.8
+/- 72.6 kcal; P = .054). A similar pattern was observed for metabolic
equivalents (HR-Match = 4.7 +/- 0.8, SELF = 4.4 +/- 0.7, YOGA = 3.6 +/- 0.6; P <
.001). Analyses using only the initial 45 minutes from each of the sessions,
which excluded the restorative component of YOGA, showed energy expenditure was
significantly lower in YOGA compared with HR-Match (difference = 68.0 +/- 40.1
kcal; P < .001) but not compared with SELF (difference = 15.1 +/- 48.7 kcal; P =
.189). CONCLUSIONS: YOGA meets the criteria for moderate-intensity physical
activity. Thus, YOGA may be a viable form of physical activity to achieve public
health guidelines and to elicit health benefits.
PMID- 28422590
TI - Localized Juvenile Spongiotic Gingival Hyperplasia: Report of Two Cases.
AB - OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a
painless gingival swelling that histologically exhibits hyperplasia of the non
keratinized stratified squamous epithelium, intercellular edema and spongiosis of
the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis
remains to be elucidated, while a possible origin from the gingival sulcus
epithelium is nowadays proposed. STUDY DESIGN: We report two cases of LJSGH with
immunohistochemical evaluation of cytokeratins (CKs) 18 and 19. RESULTS: Both
cases concerned 12-year-old boys, who presented with a well-circumscribed bright
red pedunculated papillary swelling on the marginal gingiva of the left maxillary
lateral incisor. With the provisional diagnosis of LJSGH, the lesions were
excised under local anesthesia and histological examination supported the final
diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and
mild positivity for CK19 and CK18, respectively, while the adjacent normal
gingival epithelium expressed CK19, but not CK18, only in the basal cell layer.
The postoperative course was uneventful in both patients and no recurrence has
been reported. CONCLUSION: LJSGH is a recently introduced entity that is worth
attention in the clinical pediatric dentistry. Clinical and histological
examination is required for the final diagnosis, while immunohistochemistry has
shed light to LJSGH pathogenesis.
PMID- 28422591
TI - Effect of Papacarie and Alternative Restorative Treatment on Pain Reaction during
Caries Removal among Children: A Randomized Controlled Clinical Trial.
AB - OBJECTIVE: To compare the effect of Papacarie and Atraumatic Restorative
Treatment (ART) on pain and discomfort during caries removal among children.
STUDY DESIGN: Fifty healthy, 4-8 year-old children were equally and randomly
allocated to Papacarie and ART to remove caries from decayed primary teeth. A
randomized, controlled, blinded, two parallel-arms clinical trial was conducted
in the clinic of the Pediatric Dentistry and Dental Public Health Department,
Alexandria University, Egypt in March 2014. Pain and discomfort were assessed
blindly by two independent investigators watching videotaped treatment sessions
using the Sound, Eye and Motor scale (SEM). Their reliability was assessed using
Kappa statistics. The effect of caries removal methods, time spent to remove
caries and other confounders on SEM score was assessed using regression analysis.
RESULTS: Mean time to remove caries using Papacarie and ART was 5.8 and 4.8
minutes, P= 0.005. Median Paparie and ART scores for the S, E and M components
were 1, 1, 1 and 3, 2, 3. Adjusted mean SEM score= 3.6 and 7.8, P <0.0001. Method
of caries removal was the only factor significantly affecting pain and
discomfort. CONCLUSION: Papacarie is associated with minimal pain during caries
removal from primary teeth compared to ART, although it has longer working time.
PMID- 28422592
TI - Role of Colors in Pediatric Dental Practices.
AB - OBJECTIVE: This study evaluated the association between colors and emotions in a
pediatric dental population. STUDY DESIGN: In this randomized cross-sectional
study, 100 children aged 6-12 years were categorized as non-anxious and anxious
using Corah's Dental Anxiety Scale-Revised. They were then instructed to color
two cartoon faces, one depicting happiness emotion and the other, sadness, with
any of six colors provided. Data obtained were statistically analyzed. RESULTS:
The mean Corah's Dental Anxiety scores were 11.7 and 4.97 for the anxious and non
anxious children, respectively. Both groups expressed the highest preference for
the color yellow for happiness emotion. No significant differences were observed
between color choices in either group (p>0.05), except for black which was not
chosen by any child for happiness (p<0.005). Children in both groups
significantly preferred red for sadness emotion. No significant differences were
observed between color choices in the anxious group (p>0.05). In the non-anxious
group, yellow assumed significant preference over green (p<0.05). CONCLUSIONS:
Yellow was the most-preferred color and black, the least-preferred, for happiness
emotion, whereas, for sadness emotion, red and green were the most- and least
preferred colors, respectively. Color preference was not affected by the presence
of dental anxiety.
PMID- 28422593
TI - Fundamentals in Biostatistics for Investigation in Pediatric Dentistry: Part II
Biostatistical Methods.
AB - The main purpose of the second part of this series was to provide the reader with
some basic aspects of the most common biostatistical methods employed in health
sciences, in order to better understand the validity, significance and
reliability of the results from any article on Pediatric Dentistry. Currently, as
mentioned in the first paper, Pediatric Dentists need basic biostatistical
knowledge to be able to apply it when critically appraise a dental article during
the Evidence-based Dentistry (EBD) process, or when participating in the
development of a clinical study with dental pediatric patients. The EBD process
provides a systematic approach of collecting, review and analyze current and
relevant published evidence about oral health care in order to answer a
particular clinical question; then this evidence should be applied in everyday
practice. This second report describes the most commonly used statistical methods
for analyzing and interpret collected data, and the methodological criteria to be
considered when choosing the most appropriate tests for a specific study. These
are available to Pediatric Dentistry practicants interested in reading or
designing original clinical or epidemiological studies.
PMID- 28422594
TI - Intentional Replantation of an Immature Incisor with a Transverse Root Fracture
and Endo-Perio Condition: 4 Year Follow-Up.
AB - This case report describes the importance of continual examination for dental
trauma and the efficacy of intentional replantation with retrograde root canal
filling for a transverse root fracture in an immature incisor accompanied by
subsequent periodontal-endodontic disease. In the treatment of traumatically
fractured roots in immature incisors, continual examination is indispensable for
the final diagnosis because roots in immature teeth are less calcified, resulting
in less detailed radiological examinations. Thus, common dental trauma
complications such as pulp necrosis may appear months after the initial
examination. Endodontic treatment for transverse root fracture is mainly
determined according to radiographic examination findings; for fractured immature
roots, apexification with calcium hydroxide of the coronal fragment is generally
applied. However, this method requires removal of considerable amounts of enamel
and dentin to allow access to the cavity for preparation, which may increase the
risk of future fractures. In contrast, intentional replantation with retrograde
root canal filling does not require the removal or long-term application of
calcium hydroxide. However, it requires careful extraction of the tooth,
maintenance of root wetness during the extraoral procedure, rigid splinting, and
oral hygiene control. Management of tooth mobility is also important in the post
replantation course.
PMID- 28422595
TI - Microleakage of Sealants after Phosphoric Acid, Er: YAG Laser and Air Abrasion
Enamel Conditioning: Systematic Review and Meta-Analysis.
AB - PURPOSE: The aim of this systematic review and meta-analysis is to answer the
focused question: Does the application of phosphoric acid, Er:YAG laser and air
abrasion enamel conditioning methods previous to the oclusal sealant application
in human permanent molars influence the microleakage? STUDY DESIGN: A literature
research was carried out in the Pubmed Medline, Web of Science, Scopus and
Cochrane databases using with the MeSH terms and keyword search strategy. A
supplemental hand search of the references of retrieved articles was also
performed. Inclusion criteria comprised ex vivo studies (extracted teeth) with
permanent human teeth that used chemical (phosphoric acid) or mechanical (Er:YAG
laser and air abrasion) conditioning methods previous the sealant application.
The studies should evaluate microleakage as an outcome. Meta-analysis pooled plot
were obtained comparing the microleakage after pre-treatment with phosphoric
acid, Er:YAG and air abrasion enamel conditioning for sealant application using
RevMan software. RESULTS: The search resulted in 164 articles, 55 records were
excluded because they were duplicated. The analysis of titles and abstracts
resulted in the exclusion of 105 studies. Four studies were included in the
systematic review and the meta-analysis. According to the risk of bias
evaluation, the four studies were considered low risk of bias. The meta-analysis
showed that phosphoric acid had lower microleakage than Er:YAG laser (p < 0.001)
and air abrasion (p < 0.001), with heterogeinity of I2 = 0% and I2 = 71%,
respectively. It was not found statistical difference when compared phosphoric
acid and phosphoric acid combined with Er:YAG laser and air abrasion (p > 0.05).
CONCLUSION: The evidence supports that the pretreatment with phosphoric acid
leads lower microleakage in oclusal sealants than Er:YAG laser and air abrasion.
PMID- 28422596
TI - Agenesis of Third Molars among Turkish Children between the Ages of 12 and 18
Years: A Retrospective Radiographic Study.
AB - PURPOSE: The aim of this study was to investigate the agenesis of third molars
(M3) in children with permanent dentition in a limited population in the province
of Izmir, Turkey. STUDY DESIGN: The panoramic radiographs of 773 patients (457
females, 316 males) were evaluated retrospectively at the Dental Hospital of
Ministry of Health in Izmir, Turkey. The patients' ages ranged from 12-18 years.
The agenesis of M3 teeth was investigated according to maxilla and mandible and
right and left distribution. RESULTS: In 593 of the patients (76.7%), all of the
M3 teeth were present in the mouth; while in the other 180 (23.3%) patients,
agenesis of a varying number of M3 teeth was identified. In 31 patients (4.0%),
total M3 tooth agenesis was observed. A statistically significant relationship
was not found between gender and M3 teeth (p=0.091). A statistically significant
relationship was found between congenital M3 tooth agenesis and the maxilla
(14.3%) and mandible (9.6%) (p<0.001). However, a statistically significant
difference was not found between the right-left area of the jaw (p=0.100).
CONCLUSION: As a result, while all M3 teeth were present in 76.71% of the
population studied in the province of Izmir, agenesis of one or more than one M3
tooth was found in the other 23.29% of the patients studied.
PMID- 28422597
TI - Post-Discharge Events Occurring after Dental Treatment under Deep Sedation in
Pediatric Patients.
AB - PURPOSE: Deep sedation is often required in dentistry for treating children with
uncooperative behavior. We assessed immediate post-sedation events during the
first 24 hours after dental treatment under deep sedation in children, and
examined correlations to a number of variables. STUDY DESIGN: Information was
collected from medical files for a convenience sample of children between the
ages of 1 and 16, who were treated under deep sedation at one clinic (propofol
alone or combined with a sedative agent). Parents were interviewed by telephone
regarding the first 24 hours following treatment. RESULTS: Among 32 children
under age 6 years, 26 (81.3%) had at least one post sedation complication,
compared to 19/22 (86.4%) aged 6 and older, p>0.05. According to parent report,
13 (59.1%) of the older children had pain, compared to 6 (18.8%) of the younger
ones, p=0.002. For no patient in the younger group compared to 18.2% in the older
group was dizziness reported as a complication, p=0.023. Among those who received
a sedative agent, 93.3% had one or more complications; 26.7% had nausea or
vomiting. The respective rates were 79.5% and 5.1% among those treated only with
propofol. CONCLUSIONS: Though safe, deep sedation poses complications and adverse
events.
PMID- 28422598
TI - The Use of Restorative Materials in Primary Molars among Pediatric Dentists in
Israel.
AB - OBJECTIVES: To assess the current choice of various restoration materials among
Israeli pediatric dentists according to seniority and specialty. STUDY DESIGN:
Participating dentists completed a 23-item questionnaire on their qualifications,
type of practice and preference of restorative material. RESULTS: Seventy-five
dentists (average age 46.27+/-12.6 years, 58 females) participated. Forty-one
were specialist pediatric dentists and 34 were general practitioners. Amalgam was
preferred by 49.3%, followed by composite (41.3%), glass ionomer cement (5.3%)
and compomer (4%). Only 13.3% of the dentists thought amalgam bears environmental
and health hazards, compared to 49.3% for composite. Satisfaction was high for
amalgam and composite, less for glass ionomer cements and least for compomer.
General practitioners preferred amalgam (70.6%) while pediatric dentists
preferred composite (51.2%), P < 0.003. CONCLUSIONS: Amalgam and composite were
the materials of choice among the participating Israeli dentists. Most of them
(86.7%) responded that amalgam does not possess any health issues. Their
satisfaction with the restoration materials was highest for amalgam and
composite, a choice significantly affected by whether they were in general
practice (amalgam) or specialized in pediatric dentistry (composite).
PMID- 28422599
TI - Sleep Bruxism and Anxiety Impacts in Quality of Life Related to Oral Health of
Brazilian Children and their Families.
AB - OBJECTIVE: This study aimed to assess the impact of parent reported sleep
bruxism, trait anxiety and sociodemographic/socioeconomic features on quality of
life related to oral health (OHRQoL) of children and their families. STUDY
DESIGN: Healthy children aged 3-7 years, with (n=34) and without (n=32) bruxism
were select for this study. Data was collected by applying the following
instruments: The Early Childhood Oral Health Scale (B-ECOHIS) and Trait-anxiety
Scale (TAS). The sociodemographic/socioeconomic characteristics were obtained by
interviews with parents. Multiple logistic regression tests were performed to
observe the influence of sociodemographic/socioeconomic characteristics, bruxism
and trait-anxiety on the children's OHRQoL. RESULTS: No association between sleep
bruxism and all evaluated sociodemographic/socioeconomic conditions, with
exception of being the only child (p=0.029), were observed. Mean B-ECOHIS and TAS
scores were different (p<0.05) between children with (3.41 +/- 4.87; 45.09 +/-
15.46, respectively) and without (0.63 +/- 1.28; 29.53 +/- 11.82, respectively)
bruxism. Although an association between bruxism and OHRQoL (p=0.015) was
observed, it was dropped (p=0.336; OR=1.77) in the logistic regression model.
Trait anxiety was the variable responsible for the impact on the OHRQoL of
children (p=0.012; OR=1.05). CONCLUSION: Our results indicated anxiety as the
main factor that interfered in the OHRQoL of children with sleep bruxism.
PMID- 28422600
TI - Effect of a School-Based Supervised Tooth Brushing Program In Mexico City: A
Cluster Randomized Intervention.
AB - : Large-scale school-based programs effectively provide health education and
preventive strategies. SaludARTE is a school-based program, including supervised
tooth brushing, implemented in 51 elementary schools in Mexico City. OBJECTIVES:
To assess the three-month efficacy of supervised tooth brushing in reducing
dental plaque, gingival inflammation, and bleeding on probing in schoolchildren
participating in SaludARTE. STUDY DESIGN: This was a pragmatic cluster randomized
intervention, with two parallel branches. Four randomly selected schools
participating in SaludARTE (n=200) and one control school, which did not
participate in the program (CG) (n=50), were assessed. Clusters were not randomly
allocated to intervention. The main outcomes were as follows: mean percentage
gingival units with no inflammation, dental surfaces with no dental plaque, and
gingival margins with no bleeding. The independent variable was supervised tooth
brushing at school once a day after a meal. Guardians and children responded to a
questionnaire on sociodemographic and oral hygiene practices, and children were
examined dentally. Mean percentage differences were compared (baseline and follow
up). RESULTS: A total of 75% of guardians from the intervention group (IG) and
77% from the CG answered the questionnaire. Of these, 89.3% were women, with a
mean age of 36.9+/-8.5 years. No differences in sociodemographic variables were
observed between groups, and 151 children from the IG and 35 from the CG were
examined at baseline and follow-up. Mean percentage differences for plaque-free
surfaces (8.8+/-28.5%) and healthy gingival units (23.3%+/-23.2%) were
significantly higher in the IG. CONCLUSION: The school-supervised tooth brushing
program is effective in improving oral hygiene and had a greater impact on plaque
and gingivitis than on gingival bleeding. It is necessary to reinforce the oral
health education component of the program.
PMID- 28422601
TI - Degradation of Resin Restorative Materials by Streptococcus Mutans: A Pilot
Study.
AB - OBJECTIVE: To evaluate the degradation of three resin based restorative materials
by S Mutans. STUDY DESIGN: Class I cavity was prepared in extracted premolars and
were randomly divided into 3 groups (Group I - Conventional composite (CC), Group
II - Resin Modified GIC and Group III-Giomer). Teeth were then restored by
respective restorative material and equally divided in two subgroups (Control and
Experimental). Experiment subgroup samples were then incubated in 2 ml of BHI
with 1:10 dilution of SM (MTCC-497) grown overnight in BHI whereas control
subgroup samples were incubated in BHI without SM. The incubation solution was
collected at 2,14 and 30 days interval, and the analysis for identification and
quantification of Bis-HPPP was done by High performance Liquid Chromatography.
RESULTS: Statistical analysis of the collected data revealed a statistically
increased Bis HPPP production in the presence of SM in all the tested materials,
with minimum in Resin Modified GIC and a maximum in Conventional Composite (CC).
CONCLUSION: SM degrades the resin based restorative materials & among the tested
materials Resin Modified GIC appears to be most Biostable.
PMID- 28422602
TI - Does Bonding Approach Influence the Bond Strength of Universal Adhesive to Dentin
of Primary Teeth?
AB - OBJECTIVE: To evaluate the effect of bonding strategy on microtensile bond
strength (MUTBS) of a new universal adhesive system to primary tooth dentin.
STUDY DESIGN: Flat dentin surfaces from 25 primary molars were assigned to 5
groups according to the adhesive and bonding approach: Adper Single Bond 2 (two
step etch-and-rinse adhesive) and Clearfil SE Bond (two-step self-etch system),
as controls; Scotchbond Universal Adhesive-self-etch, dry or wet-bonding etch-and
rinse strategies. Composite buildups were constructed and the teeth were
sectioned to obtain bonded sticks (0.8 mm2) to be tested under tension at
1mm/min. The MUTBS means were analyzed by one-way ANOVA and Tukey's tests (alpha
= 0.05). Failure mode was evaluated using a stereomicroscope (400*). RESULTS:
Universal adhesive applied following both dry and wet-bonding etch-and-rinse
strategies showed similar bond strength compared with control adhesive systems.
Self-etch approach resulted in the lowest MUTBS values. For all groups,
adhesive/mixed failure prevailed. The percentage of premature debonded specimens
was higher when the universal adhesive was used as self-etch mode. CONCLUSION:
The universal adhesive does not share the same versatility of being used in the
etch-and-rinse and self-etch approaches; however, the use of the new adhesive
following either wet or dry-bonding may be a suitable option as alternative to
two-step etch-and-rinse adhesive protocol.
PMID- 28422603
TI - Factors Responsible for Unfavorable Dental Arch Relationship in non Syndromic
Unilateral Cleft Lip and Palate Children.
AB - OBJECTIVES: Multiple factors are whispered to be crucial cause of unfavourable
dental arch relationship in cleft lip and palate (CLP).This study aims to
evaluate the dental arch relationship of Bangladeshi children with non syndromic
unilateral cleft lip and palate (UCLP) following cheiloplasty and palatoplasty.
Also to explore the various congenital (UCLP type, UCLP side, family history of
cleft, family history of class III) and environmental (cheiloplasty,
palatoplasty) factors that affects dental arch relationship of UCLP patients.
STUDY DESIGN: This was a retrospective study where 84 dental models were taken
before orthodontic treatment and alveolar bone grafting. The mean age was 7.69+/-
2.46 (mean+/- SD). The dental arch relationship was assessed by GOSLON (Great
Ormond Street, London and Oslo) Yardstick. According to GOSLON Yardstick, five
categories are rated; named- 1: excellent; 2: good; 3: fair; 4: poor; 5: very
poor. Also the groups have been dichotomized into favorable (category ratings 1
3) and unfavorable (category ratings 4 and 5) groups. Kappa statistics was used
to evaluate the intra- and inter-examiner agreements and logistic regression
analysis was used to explore the responsible factors that affect dental arch
relationship. RESULTS: Total 37 subjects (44% of all subjects) were categorized
into unfavourable group (category rating 4 and 5) using GOSLON yardstick. Intra-
and inter-examiner agreements were very good. The mean GOSLON score was 3.238.
Using crude and stepwise backward regression analysis, significant association
was found between family history of skeletal class III malocclusion (p = 0.015
and p = 0.014 respectively) and unfavourable dental arch relationship. Complete
UCLP (p = 0.054) and left sided UCLP (p = 0.053) also seemed to be correlated but
not significant with unfavourable dental arch relationship using crude and
stepwise backward regression analysis respectively. CONCLUSION: This analysis
suggested that family history of skeletal class III was significantly correlated
with unfavourable dental arch relationship of Bangladeshi UCLP children.
PMID- 28422604
TI - Examination of Intramuscular and Skin Temperature Decreases Produced by the
PowerPlay Intermittent Compression Cryotherapy.
AB - CONTEXT: Previous research has found ice bags are more effective at lowering
intramuscular temperature than gel packs. Recent studies have evaluated
intramuscular temperature cooling decreases with ice bag versus Game Ready and
with the PowerPlay system wetted ice bag inserts; however, intramuscular
temperature decreases elicited by PowerPlay with the standard frozen gel pack
inserts have not been examined. OBJECTIVE: Evaluate the rate and magnitude of
cooling using PowerPlay with frozen gel pack (PP-gel) option, PowerPlay with
wetted ice bag (PP-ice) option, and control (no treatment) on skin and
intramuscular temperature (2 cm subadipose). DESIGN: Repeated-measures
counterbalanced study. SETTING: University research laboratory. PATIENTS OR OTHER
PARTICIPANTS: Twelve healthy college-aged participants (4 men and 8 women; age =
23.08 (1.93) y, height = 171.66 (9.47) cm, mass = 73.67 (13.46) kg, and
subcutaneous thickness = 0.90 (0.35) cm). INTERVENTION(S): PowerPlay (70 mm Hg)
with either wetted ice bag or frozen gel pack was applied to posterior aspect of
nondominant calf for 30 minutes; control lay prone for 30 minutes. Participants
underwent each treatment in counterbalanced order (minimum 4 d, maximum 10 d
between). MAIN OUTCOME MEASURE(S): Muscle temperature was measured via 21-gauge
catheter thermocouple (IT-21; Physitemp Instruments, Inc). Skin temperature was
measured via surface thermocouple (SST-1; Physitemp Instruments, Inc). RESULTS:
Significant treatment-by-time interaction for muscle cooling (F10,80 = 11.262, P
= .01, [Formula: see text], observed beta = 0.905) was observed. PP-ice cooled
faster than both PP-gel and control from minutes 12 to 30 (all Ps < .05); PP-gel
cooled faster than control from minutes 18 to 30 (all Ps < .05). Mean decreases
from baseline: PP-ice = 4.8 degrees C (2.8 degrees C), PP-gel = 2.3 degrees C
(0.8 degrees C), and control = 1.1 degrees C (0.4 degrees C). Significant
treatment-by-time interaction for skin cooling (F10,80 = 23.920, P = .001,
[Formula: see text], observed beta = 0.998) was observed. PP-ice cooled faster
than both PP-gel and control from minutes 6 to 30 (all Ps < .05); PP-gel cooled
faster than control from minutes 12 to 30 (all Ps < .05). Mean decreases from
baseline: PP-ice = 14.6 degrees C (4.8 degrees C), PP-gel = 4.0 degrees C (0.9
degrees C), and control = 1.0 degrees C (1.0 degrees C). CONCLUSIONS: PP-ice
produces clinically and statistically greater muscle and skin cooling compared
with PP-gel and control.
PMID- 28422605
TI - Time to First Cigarette, Physical Activity, and Pulmonary Function in Middle-aged
to Older Adult Smokers.
AB - BACKGROUND: How addiction severity relates to physical activity (PA), and if PA
moderates the relation between PA and lung function among smokers, is unknown.
This study explored the independent and interactive associations of nicotine
addiction severity and PA with lung function. METHODS: The study used cross
sectional data from 343 adult smokers aged 40 to 79 participating in the 2009-10
and 2011-12 National Health and Nutrition Examination Survey. Assessed were the
independent relations of nicotine addiction severity, as measured by the time to
first cigarette (TTFC), and average daily minutes of moderate and vigorous PA
with lung function ratio (FEV1/FVC). Additional analysis examined whether PA
moderated the relationship between addiction severity and lung function. RESULTS:
Greater lung function was independently associated with moderate PA and later
TTFC, but not vigorous PA, when controlling for cigarettes per day (CPD), past
month smoking, ethnicity, years smoked, and gender (P-values < .05). PA did not
moderate the association between addiction severity (TTFC) and lung function (P =
.441). CONCLUSION: Among middle-aged to older smokers, increased PA and lower
addiction severity were associated with greater lung function, independent of
CPD. This may inform research into the protective role of PA and identification
of risk factors for interventions.
PMID- 28422606
TI - Secular Mindfulness-Based Interventions: Efficacy and Neurobiology.
PMID- 28422607
TI - Delusional Disorder Arising From a CNS Neoplasm.
AB - Erotomania arising from a central nervous system (CNS) neoplasm has not been
previously described. Here, we present the first known case, to our knowledge, of
erotomania with associated persecutory delusions arising following diagnosis and
treatment of a left frontal lobe brain tumor.
PMID- 28422608
TI - Six new soil-inhabiting Cladosporium species from plateaus in China.
AB - Cladosporium species are ubiquitous in various environments but are hitherto
rarely isolated from soil. In the present study, six new Cladosporium species
inhabiting the plateau soils of China are described as C. neopsychrotolerans, C.
paralimoniforme, C. prolongatum, C. sinuatum, C. tianshanense, and C.
verruculosum. These species are phylogenetically distinct and morphologically
different from known species. This study increased the number of species
classified in the C. cladosporioides and C. herbarum complexes and revealed
Chinese plateau soil as a rich niche of Cladosporium species diversity.
PMID- 28422610
TI - Joint bent-cable Tobit models for longitudinal and time-to-event data.
AB - In this article, we show how to estimate a transition period for the evolvement
of drug resistance to antiretroviral (ARV) drug or other related treatments in
the framework of developing a Bayesian method for jointly analyzing time-to-event
and longitudinal data. For HIV/AIDS longitudinal data, developmental trajectories
of viral loads tend to show a gradual change from a declining trend after
initiation of treatment to an increasing trend without an abrupt change. Such
characteristics of trajectories are also associated with a time-to-event process.
To assess these clinically important features, we develop a joint bent-cable
Tobit model for the time-to-event and left-censored response variable with
skewness and phasic developments. Random effects are used to determine the
stochastic dependence between the time-to-event process and response process. The
proposed method is illustrated using real data from an AIDS clinical study.
PMID- 28422609
TI - Isotemporal Analysis of the Association of Objectively Measured Physical Activity
With Depressive Symptoms: Results From Hispanic Community Health Study/Study of
Latinos (HCHS/SOL).
AB - BACKGROUND: The burden of depression among Hispanics/Latinos indicates the need
to identify factors related to depressive symptoms. This paper examines the
relationship of physical activity (PA) and sedentary behavior (SB) with
depressive symptoms in Hispanic/Latinos. METHODS: The Hispanic Community Health
Study / Study of Latinos (HCHS/SOL) is a population-based, cohort study of
Hispanic/Latinos in 4 United States metropolitan areas. Objectively measured PA
was coded into: sedentary behavior (SB), light-intensity (LPA), moderate
intensity (MPA), and vigorous-intensity (VPA); and the Center for Epidemiological
Studies Depression Scale-10 assessed depressive symptoms. Multiple regression
analysis utilizing isotemporal substitution, adjusted for relevant covariates,
examined PA as predictors of depressive symptoms. RESULTS: Substitution of 1 hour
of SB with VPA resulted in a significant decrease in depressive symptoms (beta =
1.215, P = .021). Similar decreases were observed when VPA replaced LPA (beta =
1.212, P = .021) and MPA (beta = -1.50 P = .034). MPA and LPA were not associated
with lower depressive symptoms. CONCLUSIONS: Previous research has focused on the
relationship of MVPA on depressive symptoms. Our results suggest these constructs
should be examined separately as they may have unique relationships with
depressive symptoms. The association of SB with greater depressive symptoms
confirms previous reports.
PMID- 28422611
TI - Predictors of Hearing Protection Use Among Industrial Workers.
AB - Promoting the use of hearing protection devices (HPDs) can prevent noise-induced
hearing loss (NIHL) among workers who are exposed to excessive noise. In the
present study, the authors examine factors that may explain HPD use among
industrial workers from 15 manufacturing plants in Thailand. Participants
consisted of 268 randomly selected workers exposed to harmful noise levels for
which routine HPD use was required. Logistic regression analysis of study
variables revealed the most powerful predictors of HPD use were perceived hearing
status ( b = 0.66, p < .001) and interpersonal factors (i.e., role modeling and
interpersonal support; b = 0.20, p < .001). Together, these variables correctly
classified 63.4% of the cases. These findings have implications for interventions
aimed at motivating workers to use HPDs regularly.
PMID- 28422612
TI - Assessing Non-Suicidal Self-Injury in the Laboratory.
AB - The majority of non-suicidal self-injury (NSSI) research has used self- or
clinician-rated measures of behavior which (a) are subject to reporting biases,
or (b) have limited use in experimental designs that could illuminate causal
relationships. Laboratory-based behavioral tasks have therefore been developed to
assess NSSI-related behaviors more directly. We reviewed the behavioral methods
that have been developed to assess NSSI tendencies or behaviors over the past 30
years. Several categories of laboratory analogues were identified: NSSI-related
stimuli (e.g., NSSI pictures, implicit association tasks, guided imagery),
experimenter administered pain stimuli (e.g., cold, heat, pressure, shock, and
blade), and self-selected pain stimuli (e.g., cold and shock). These behavioral
methods assess various aspects of NSSI and all have distinct advantages and
shortcomings. Overall, these approaches have made significant contributions to
the field complementing self- and clinician-ratings.
PMID- 28422613
TI - The Impact of Prospective Telemedicine Implementation in the Management of
Childhood Acute Lymphoblastic Leukemia in Recife, Brazil.
AB - BACKGROUND: A gap in childhood cancer outcomes remains between developed and
developing countries. Persistence of this gap may be caused by financial, social,
or educational disparities. Twinning and distance learning initiatives may
improve such disparities. Integrating telemedicine into pediatric oncology
twinning programs enhances education and facilitates patient-centered capacity
building. MATERIALS AND METHODS: We performed an analysis of Web-based meetings
held from August 2005 through July 2009 between the International Outreach
Program at St. Jude Children's Research Hospital and the Instituto Materno
Infantil de Pernambuco (IMIP) in Recife, Brazil. We determined the effect of
these online conferences on the development and implementation of an innovative
protocol for children with acute lymphoblastic leukemia (ALL) at IMIP. RESULTS:
Meetings occurred in 45 months of the 48-month study period with an average of
two meetings per month. A total of 163 new patients were discussed during the
study period; we retrieved documentation of patient-related discussions for 147
of them, constituting 286 discussions. On average, each patient was discussed 1.9
times (range, 1-15 discussions/patient). Compared with that of the era predating
the online meetings (1993-2005), overall mortality, early death, and relapse of
patients with ALL decreased after the telemedicine program was instituted at
IMIP. DISCUSSION: Personal dedication and institutional support are essential for
successful telemedicine initiatives. Documentation and archival of meetings are
important for accurately measuring outcomes and developing methods for improved
care. CONCLUSIONS: Integration of telemedicine into twinning programs facilitates
communication about interventions, leading to improved outcomes of pediatric
patients with cancer.
PMID- 28422614
TI - Electronic Follow-Up of Developing World Cleft Patients: A Digital Dream?
AB - OBJECTIVE: To identify potential access to telemedicine follow-up of children
with clefts operated on a humanitarian mission. METHODS: A cross-sectional study
of parents of children presenting to a humanitarian cleft lip and palate mission
in a Provincial Hospital in the Philippines. A purpose designed questionnaire was
used to assess access to electronic and digital resources that could be used to
aid follow-up. Forty-five (N = 45) parents of children having primary cleft lip
and or palate surgery participated. There were no interventions. Access to the
Internet was through Parent Perceived Affordability of Internet Access and Parent
Owned Devices. RESULTS: Thirty-one (N = 31) respondents were female. There was
93% mobile phone ownership. The mean distance traveled to the clinic was 187 km.
Majority (56%) were fluent in English. Thirty-one percent accessed the Internet
daily. Sixteen percent reported use of e-mail. Fifty-one percent accessed the
Internet on a mobile device, and short message service use was the most
affordable means of communication. CONCLUSIONS: Due to perceived unaffordability
and low levels of access to devices with cameras and the Internet, as well as
issues with privacy, we cannot recommend relying on electronic follow-up of
patients in the developing world.
PMID- 28422615
TI - Understanding How Sexual and Gender Minority Stigmas Influence Depression Among
Trans Women and Men Who Have Sex with Men in India.
AB - PURPOSE: Few studies have assessed how sexual and gender minority stigmas affect
the mental health of trans women and self-identified men who have sex with men
(MSM) in India, populations with a high HIV burden. We tested whether social
support and resilient coping act as mediators of the effect of sexual and gender
minority stigmas on depression as proposed by Hatzenbuehler's psychological
mediation framework, or as moderators based on Meyer's minority stress theory.
METHODS: We conducted a cross-sectional survey among trans women (n = 300) and
MSM (n = 300) recruited from urban and rural sites in India. Standardized scales
were used to measure depression (outcome variable), transgender identity
stigma/MSM stigma (predictor variables), and social support and resilient coping
(tested as moderators and parallel mediators). The mediation and moderation
models were tested separately for trans women and MSM, using Hayes' PROCESS macro
in SPSS. RESULTS: Participants' mean age was 29.7 years (standard deviation 8.1).
Transgender identity stigma and MSM stigma were significant predictors
(significant total and direct effects) of depression, as were social support and
resilient coping. Among trans women and MSM, social support and resilient coping
mediated (i.e., significant specific indirect effects), but did not moderate, the
effect of stigma on depression, supporting the psychological mediation framework.
CONCLUSION: Sexual and gender minority stigmas are associated with depression,
with social support and resilient coping as mediators. In addition to stigma
reduction interventions at the societal level, future interventions should focus
on improving social support and promoting resilience among trans women and MSM in
India.
PMID- 28422616
TI - To Give Epinephrine or Not to Give Epinephrine-That Is (No Longer) The Question!
AB - It is vital that school nurses be able to assess students who are at risk for
anaphylaxis and that nurses train school staff to identify the symptoms of a life
threatening allergic reaction. When a reaction occurs, school nurses and staff
must be prepared to administer epinephrine immediately.
PMID- 28422617
TI - Hidden Devices in the School Setting: What the Nurse Needs to Know About Shunts.
AB - The role of school nurse today not only includes making a thorough assessment of
the child but also the knowledge and skill to understand hidden medical devices.
As of 2011, there were approximately 14.6 million children in the United States
living with special health care needs. Many of these children could have hidden
medical devices. The Specialized Health Needs Interagency Collaboration (SHNIC)
program at the Kennedy Krieger Institute received requests for in-person training
regarding ventriculoperitoneal (VP) shunts.
PMID- 28422618
TI - School Nurses on the Front Lines of Medicine: Connecting the Dots: SCRIPTS for
Success in the Evaluation of Pediatric Rashes.
AB - Although skin rashes may not necessarily prompt a visit to the school nurse's
office, a rash associated with other systemic symptoms, such as fever, headache,
difficulty swallowing or breathing, weakness, or abdominal pain, may cause a
child to visit your office. This article describes the initial assessment and
management of skin rashes in children and adolescents and delineates reasons that
may prompt the school nurse to transfer a student with a rash to a local
emergency department.
PMID- 28422619
TI - The Role of the School Nurse in the Special Education Process: Part I: Student
Identification and Evaluation.
AB - Every U.S. student is entitled to a free and appropriate education. School
districts must identify and evaluate any child who they find is unable to engage
fully in learning as a participant in the general education curriculum. The
Individuals with Disabilities Education Act of 2004 requires that these students
be assessed by qualified individuals in any areas that may be impacting learning,
including health, vision, hearing, social and emotional status, communicative
status, and motor abilities. The school nurse, as the health expert, has an
important role to play as a member of the special education team in evaluating
whether a student has health concerns that are impacting learning and how health
barriers to learning might be reduced. As part of the full and individual
evaluation, the school nurse composes a written report and makes recommendations
to the team regarding necessary health services and other modifications the
student may need. This article (Part 1 of 2) will outline the school nurse's role
in identification and evaluation of students who may benefit from special
education services.
PMID- 28422620
TI - The Time Has Come for School Nurses and Social Media.
PMID- 28422621
TI - Historic Leadership: One Courageous School Nurse's Heroic Journey-Part 3.
AB - School nursing practice establishes itself in the midst of both education and
nursing philosophies, ethics, standards, laws, and regulations. Treading these
two worlds is difficult at times and requires that a school nurse possess a
strong foundational knowledge base, seek professional collaboration, and navigate
conflicting professional demands in order to promote student and public safety.
This article is Part 3 of a four-part series that recounts the inspiring story of
a school nurse, Ellen Johnsen, who did just that back in the 1980s in Broken
Arrow, Oklahoma. Part 3 describes the publication of the Attorney General's
opinion validating the illegality of the school district's medication
administration policy, the lawsuit Ellen brought against the Broken Arrow Public
Schools, and the appeal of the final decision in that lawsuit. The purpose of
this series is to enhance understanding of the legal parameters governing school
nurse practice, provide examples of ethical decision making, and review the
challenges associated with serving as a leader.
PMID- 28422622
TI - Framework for 21st Century School Nursing Practice: Framing Professional
Development.
AB - The NASN Code of Ethics upholds that it is the responsibility of the school nurse
to maintain competency and pursue personal and professional growth. Designing
professional development activities that are relevant and support the needs of
the school nurse can be a challenge. The Framework for 21st Century School
Nursing Practice provides a model rooted in evidence-based standards of practice
that can be utilized to assess an existing professional development program and
identify gaps in learning opportunities. Nurse leaders can use the Framework for
21st Century Nursing Practice to provide a roadmap toward a professional
development program that will be meaningful to school nurse staff, help restore
or maintain joy in their practice, and allow them to achieve the goal of
advancing the well-being, academic success, and lifelong achievement and health
of students.
PMID- 28422623
TI - Knee stiffness and viscosity: New implementation and perspectives in prosthesis
development.
AB - The pendulum test is a method applied to measure passive resistance of the knee.
A new and simple pendulum test with instrumentation based on infrared camera was
used to evaluate knee stiffness and viscosity on a female human cadaver. The
stiffness and viscosity were calculated based on the kinetic data. During the
measurements, the periarticular and intraarticular soft tissue of the knee was
gradually removed to determine the stiffness and viscosity as a function of the
tissue removal rate. The measurements showed that the removal of tissue around
the joint reduces the damping of leg oscillation, and therefore decreases the
stiffness and viscosity. The contribution to knee joint damping was 10% for the
skin, 20% for ligaments, and 40% for muscles and tendons. Tissue removal has a
very large impact on the knee stiffness and viscosity.
PMID- 28422624
TI - Occupational Therapy's Role in Cancer Survivorship as a Chronic Condition.
AB - Improved medical care has resulted in a documented increase in cancer survivors
in the United States. Cancer survivors face challenges in participation across
all facets of life as a result of the cancer and subsequent cancer treatments.
Long-term and late-term sequelae can result in impairments in neurological
systems, decreased stamina, loss of range of motion, and changes in sensation and
cognition. These impairments are often long lasting, which categorizes cancer
survivorship as a chronic condition. This categorization presents treatment
challenges, especially in creating rehabilitation and habilitation service
options that support cancer survivors. Occupational therapy provides a unique
focus that can benefit cancer survivors as they face limitations in participation
in all aspects of daily living. Research, advocacy, and education efforts are
needed to focus on the specific rehabilitation and habilitation needs of cancer
survivors to increase access to occupational therapy's distinct value.
PMID- 28422625
TI - Characteristics of Students Receiving Occupational Therapy Services in Transition
and Factors Related to Postsecondary Success.
AB - OBJECTIVE: This study had a twofold purpose: (1) identify the characteristics of
people with disabilities who received occupational therapy services during their
transition to adulthood and (2) determine factors associated with their
successful postsecondary transition. METHOD: This study was a secondary analysis
of National Longitudinal Transition Study-2 data. Data analyses include
descriptive statistics, binary logistic regression, and simple linear regression.
RESULTS: Autism, cerebral palsy, and intellectual disability were the most
commonly reported disability classifications. Participation in postsecondary
education was significantly associated with functional use of arms and hands.
Postsecondary employment was significantly associated with verbal comprehension.
Participation in community activities was significantly related to students'
health status, and participation in community service was significantly related
to students' functional use of arms and hands. CONCLUSION: Providing transition
services to students with disabilities remains an emerging area of practice.
Occupational therapy practitioners may contribute to transition teams by
intervening to improve functional abilities and health status.
PMID- 28422626
TI - Navigating the Hidden Curriculum of Higher Education for Postsecondary Students
With Intellectual Disabilities.
AB - Students with intellectual and/or developmental disabilities (IDD) increasingly
pursue postsecondary education (PSE). Navigating the hidden curriculum-including
meeting prerequisites for PSE and employment, using support systems and community
transportation, and carrying out adulthood expectations-is an area of challenge.
This exploratory case study examined experiences of students with IDD attending a
PSE program and stakeholder perspectives. Thirty-two participants (10 students
with IDD, 5 parents or guardians, 4 college administrators, 8 college
instructors, 4 occupational therapists, and a transition specialist) were
interviewed. Conventional content analysis revealed navigating the hidden
curriculum as a key theme and three subthemes: (1) adult-based system navigation,
(2) persisting challenges with adaptive behaviors, and (3) disability awareness
and disclosure. Limited awareness of disability and supports and services needed
for a successful PSE outcome were contributing factors. Occupational therapists
have the skills to support students with IDD in skill acquisition to successfully
transition to and navigate PSE and the hidden curriculum.
PMID- 28422627
TI - Quality of Life Perspectives of People With Amyotrophic Lateral Sclerosis and
Their Caregivers.
AB - This study explored differences in perspectives on quality of life (QOL) between
people affected by amyotrophic lateral sclerosis (ALS) and their caregivers. QOL
is often thought of as related to physical limitations, without consideration of
other factors (e.g., cognitive, emotional) that may be stronger predictors of QOL
in people with long-term degenerative diseases. Because QOL is complex and
influenced by multiple factors, people with ALS and their caregivers may have
different perspectives on what constitutes QOL. This study investigated potential
discrepancies in QOL perspectives between people with ALS and their caregivers.
Thirty dyads from the Augusta University Health ALS Clinic completed a measure of
QOL, and we compared the results and identified patterns. The most prominent
finding was that members of the dyads misunderstood the mental experiences of one
another.
PMID- 28422628
TI - Occupational Performance Coaching for Stroke Survivors: A Pilot Randomized
Controlled Trial.
AB - OBJECTIVE: We examined the feasibility of study procedures and explored the
potential efficacy of Occupational Performance Coaching for stroke survivors (OPC
Stroke), an intervention designed to improve participation after stroke. METHOD:
In this pilot randomized controlled trial, 21 participants were randomized to
receive the intervention or usual care. Recruitment, retention, and outcome
completion rates were calculated. Direction of change and effect sizes were
examined for the outcomes of participation, goal performance and satisfaction,
goal self-efficacy, emotional well-being, and cognition. RESULTS: Rates of
recruitment (66%) and retention (81%) were satisfactory. Participation scores
improved for both groups with different trajectories. Results showed a moderate
effect of OPC-Stroke for goal performance (eta2partial d = .075) and satisfaction
(eta2partial d = .078) and a large effect for cognition (eta2partial d = .167).
Other outcome measures did not change as expected. CONCLUSION: Study procedures
were generally feasible. Preliminary findings support testing to examine the
efficacy of OPC-Stroke.
PMID- 28422629
TI - Development and Alternate Form Reliability of the Complex Task Performance
Assessment (CTPA) for People With Mild Stroke.
AB - Cognitive impairment is a common consequence of mild stroke. Current performance
based assessments for mild stroke can detect mild impairments in executive
function but lack alternate forms to be used as outcome measures. This study
aimed to develop an alternate form of the Complex Task Performance Assessment
(CTPA-Alt), a performance-based assessment of executive function, and to
establish the alternate form reliability of the CTPA-Alt. A repeated-measures
study was conducted with 26 community participants. Participants were screened
for eligibility and administered both forms of the CTPA; administration order was
alternated. Overall performance was significantly correlated (rs = .44, p = .03),
but pattern of scoring differed by CTPA form and order of administration. Our
results indicate that the CTPA forms were similar but that the specific tasks in
each form were different. The CTPA may be used as an ecologically valid outcome
assessment with further considerations.
PMID- 28422630
TI - Feasibility of Pediatric Game-Based Neurorehabilitation Using Telehealth
Technologies: A Case Report.
AB - This case report is the first in a series of reports designed to determine the
feasibility of implementing game-based neurorehabilitation using telehealth
technologies (GbN+TT) for children with cerebral palsy, evaluate the
responsiveness of relevant outcome measures to changes in motor impairment and
activity participation after intervention, and identify technological challenges
associated with implementation of GbN+TT. The participant completed more than 56
hr of game-based neurorehabilitation over 8 wk using the Timocco platform in his
home. The primary measures of motor impairment (Bruininks-Oseretsky Test of Motor
Proficiency, Second Edition) and function (Pediatric Motor Activity Log) were
both sensitive to change. Results indicate that it is feasible to administer
GbN+TT to a child with cerebral palsy and monitor outcomes using standardized
assessments.
PMID- 28422631
TI - Do Neglect Assessments Detect Neglect Differently?
AB - OBJECTIVE: We determined whether various assessment tools detect neglect
differently by administering a battery of assessments to people with stroke.
METHOD: We conducted a case series study and administered five neglect
assessments (paper-and-pencil, functional, virtual reality) to participants
poststroke. RESULTS: Twelve participants (6 men, 6 women) with stroke completed
the assessment battery, which required approximately 2 hr to administer (over one
to two sessions). All participants demonstrated neglect on three or more
assessments. Functional assessments and the virtual reality assessment detected
neglect more frequently than the paper-and-pencil assessments. Participants
performed differently on the paper-and-pencil assessments and functional
assessments. CONCLUSION: Because neglect is complex, detection may depend largely
on the assessment administered.
PMID- 28422632
TI - Somatosensory Discrimination Intervention Improves Body Position Sense and Motor
Performance in Children With Hemiplegic Cerebral Palsy.
AB - OBJECTIVE: This study examined the use of the adult neuroscience-based Sense(c)
intervention with children with hemiplegic cerebral palsy (HCP) to improve upper
limb somatosensory discrimination, motor function, and goal performance. METHOD:
Seventeen children with HCP (9 boys, 8 girls; mean age = 10.2 yr) participated in
this pilot matched-pairs trial with random allocation and 6-mo follow-up
(intervention, n = 7; control, n = 10). The intervention group received Sense
training 3*/wk for 6 wk (18 hr). Outcome measures included Goal Attainment
Scaling, Sense_assess(c) Kids, and the Assisting Hand Assessment. RESULTS: The
intervention group improved in goal performance, proprioception, and bimanual
hand use and maintained improvement at 6-mo follow-up. The control group improved
in occupational performance by 6-mo follow-up. CONCLUSION: This study established
the feasibility of using the Sense intervention in a pediatric setting and adds
preliminary evidence to suggest that improving somatosensory function can improve
motor function and goal performance among children with HCP.
PMID- 28422633
TI - Change in Functional Arm Use Is Associated With Somatosensory Skills After
Sensory Retraining Poststroke.
AB - OBJECTIVE: We investigated changes in functional arm use after retraining for
stroke-related somatosensory loss and identified whether such changes are
associated with somatosensory discrimination skills. METHOD: Data were pooled (N
= 80) from two randomized controlled trials of somatosensory retraining. We used
the Motor Activity Log to measure perceived amount of arm use in daily activities
and the Action Research Arm Test to measure performance capacity. Somatosensory
discrimination skills were measured using standardized modality-specific
measures. RESULTS: Participants' arm use improved after somatosensory retraining
(z = -6.80, p < .01). Change in arm use was weakly associated with
somatosensation (tactile, beta = 0.31, p < .01; proprioception, beta = -0.17, p >
.05; object recognition, beta = 0.13, p < .05). CONCLUSION: Change in daily arm
use was related to a small amount of variance in somatosensory outcomes. Stroke
survivors' functional arm use can increase after somatosensory retraining, with
change varying among survivors.
PMID- 28422634
TI - Functional Brain Stimulation in a Chronic Stroke Survivor With Moderate
Impairment.
AB - OBJECTIVE: To determine the impact of transcranial direct current stimulation
(tDCS) combined with repetitive, task-specific training (RTP) on upper-extremity
(UE) impairment in a chronic stroke survivor with moderate impairment. METHOD:
The participant was a 54-yr-old woman with chronic, moderate UE hemiparesis after
a single stroke that had occurred 10 yr before study enrollment. She participated
in 45-min RTP sessions 3 days/wk for 8 wk. tDCS was administered concurrent to
the first 20 min of each RTP session. RESULTS: Immediately after intervention,
the participant demonstrated marked score increases on the UE section of the Fugl
Meyer Scale and the Motor Activity Log (on both the Amount of Use and the Quality
of Movement subscales). CONCLUSION: These data support the use of tDCS combined
with RTP to decrease impairment and increase UE use in chronic stroke patients
with moderate impairment. This finding is crucial, given the paucity of
efficacious treatment approaches in this impairment level.
PMID- 28422635
TI - Simulated Driving Skills Evaluation of Teenagers With Attention Deficit
Hyperactivity Disorder Before Driving Lessons.
AB - OBJECTIVE: We evaluated the driving skills of teenagers with attention deficit
hyperactivity disorder (ADHD) during simulated driving before starting driving
lessons and observed whether methylphenidate (MPH) affected their performance.
METHOD: Sixty teenagers ages 15-18 yr were included; 29 teenagers with ADHD were
tested with and without MPH, and 31 teenagers (control group) were tested once.
All participants were tested on the STISIM DriveTM simulator. RESULTS: The number
of center-line crossings was higher in the group without MPH treatment than in
the control group and the MPH-treated group. The group without MPH treatment had
more road-edge excursions compared with the control group and drove faster than
the MPH-treated group. CONCLUSION: Adolescents with ADHD without MPH treatment
demonstrated impaired performance more often while driving the simulator,
resembling characteristics found during on-road driving among teenagers with
ADHD. Trainer awareness is a primary intervention before taking driving lessons
to help teenagers achieve safe driving performance.
PMID- 28422636
TI - Impact of PANS and PANDAS Exacerbations on Occupational Performance: A Mixed
Methods Study.
AB - OBJECTIVE: Pediatric acute-onset neuropsychiatric syndrome (PANS) includes
pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infections and involves sudden-onset neuropsychiatric symptoms, including
obsessions, compulsions, sensory difficulties, and dysgraphia after infection or
other triggers. Our objective was to identify problems with areas of occupation,
body functions, and performance skills during exacerbations. METHOD: In this
online retrospective study, based on the Occupational Therapy Practice Framework:
Domain and Process (2nd ed.), we surveyed parents of 111 children with PANS.
RESULTS: Activities of daily living, math, handwriting, extracurricular
activities, free play, organized sports, community and family social
participation, higher level thinking, attention, memory, sequencing, emotional
coping, and energy and drive were commonly affected during exacerbations. During
exacerbations, children often required assistance and adaptation to remain
functional or were unable to function at a typical level. CONCLUSION: Children
with PANS present with pervasive occupational performance needs during
exacerbation. Children and families may benefit from accommodations to maximize
function during this turbulent period.
PMID- 28422637
TI - Embedding Questions During Online Lecture Capture to Promote Learning and
Transfer of Knowledge.
AB - We examined the effect of quizzing on students' ability to apply lecture content
to clinical examples on an in-class exam. Fifty-six occupational therapy students
in a graduate-level course completed three online modules that included lectures,
slide presentations, demonstrations, and video clips. Throughout each module,
students were given "Learning Moments," in which they were asked a question
(Question condition); were asked to read a statement confirming the content
presented (Study condition); or were not asked to do anything (Not Asked
condition). The Question condition resulted in better exam performance than the
combined Study and Not Asked conditions (p < .01), whereas performance on Study
and Not Asked questions did not differ (p = .67). Students performed better on
material on which they had been previously quizzed (i.e., testing effect).
Quizzing may be a good strategy to prepare students for clinical practice.
PMID- 28422638
TI - Resource Seeking as Occupation: A Critical and Empirical Exploration.
AB - Occupational therapists and occupational scientists are committed to generating
and using knowledge about occupation, but Western middle-class social norms
regarding particular ways of doing have limited explorations of survival
occupations. This article provides empirical evidence of the ways in which
resource seeking constitutes an occupational response to situations of uncertain
survival. Resource seeking includes a range of activities outside formal
employment that aim to meet basic needs. On the basis of findings from 2
ethnographic studies, we critique the presumption of survival in guiding
occupational therapy documents and the accompanying failure to recognize
occupations that seem at odds with self-sufficiency. We argue that failing to
name resource seeking in occupational therapy documents risks alignment with
social, political, and economic trends that foster occupational injustices. If
occupational therapists truly aim to meet society's occupational needs, they must
ensure that professional documents and discourses reflect the experiences of all
people in society.
PMID- 28422639
TI - Rehabilitation Research at the National Institutes of Health: Moving the Field
Forward (Executive Summary).
AB - Approximately 53 million Americans live with a disability. For decades, the
National Institutes of Health (NIH) has been conducting and supporting research
to discover new ways to minimize disability and enhance the quality of life of
people with disabilities. After the passage of the Americans With Disabilities
Act, NIH established the National Center for Medical Rehabilitation Research,
with the goal of developing and implementing a rehabilitation research agenda.
Currently, 17 institutes and centers at NIH invest more than $500 million per
year in rehabilitation research. Recently, the director of NIH, Francis Collins,
appointed a Blue Ribbon Panel to evaluate the status of rehabilitation research
across institutes and centers. As a follow-up to the work of that panel, NIH
recently organized a conference, "Rehabilitation Research at NIH: Moving the
Field Forward." This report is a summary of the discussions and proposals that
will help guide rehabilitation research at NIH in the near future.
PMID- 28422640
TI - National Institutes of Health Research Plan on Rehabilitation.
AB - One in 5 Americans experiences disability that affects daily function because of
impairments in mobility, impairments in cognitive function, sensory impairment,
or communication impairment. The need for rehabilitation strategies to optimize
function and reduce disability is a clear priority for research to address this
public health challenge. The National Institutes of Health (NIH) recently
published a Research Plan on Rehabilitation that provides a set of priorities to
guide the field over the next 5 years. The plan was developed with input from
multiple institutes and centers within the NIH, the National Advisory Board for
Medical Rehabilitation Research, and the public. This article provides an
overview of the need for this research plan, an outline of its development, and a
listing of six priority areas for research.
PMID- 28422641
TI - Supporting Stroke Motor Recovery Through a Mobile Application: A Pilot Study.
AB - Neuroplasticity and motor learning are promoted with repetitive movement,
appropriate challenge, and performance feedback. ARMStrokes, a smartphone
application, incorporates these qualities to support motor recovery. Engaging
exercises are easily accessible for improved compliance. In a multiple-case,
mixed-methods pilot study, the potential of this technology for stroke motor
recovery was examined. Exercises calibrated to the participant's skill level
targeted forearm, elbow, and shoulder motions for a 6-wk protocol. Visual,
auditory, and vibration feedback promoted self-assessment. Pre- and posttest data
from 6 chronic stroke survivors who used the app in different ways (i.e., to
measure active or passive motion, to track endurance) demonstrated improvements
in accuracy of movements, fatigue, range of motion, and performance of daily
activities. Statistically significant changes were not obtained with this pilot
study. Further study on the efficacy of this technology is supported.
PMID- 28422642
TI - Detection and Treatment of Autism Spectrum Disorder by Occupational Therapy
Practitioners: Addressing Racial Disparity in Diagnosis.
AB - As the prevalence of autism spectrum disorder (ASD) continues to rise, racial
disparities remain in age of diagnosis and initiation of treatment. Therefore,
occupational therapy practitioners should examine cultural perceptions related to
disparities in ASD diagnosis. This article investigates the role that
practitioners may play in this disparity by asking, "Are occupational therapy
practitioners contributing to the late diagnosis of children with ASD who are
members of particular racial or ethnic groups?" Correlations among practitioners'
detection of symptoms, parents' perceptions, and evaluator influences are
investigated. By examining these factors, practitioners may gain better insight
into these disparities and therefore provide more effective advocacy regarding
early diagnosis and treatment access.
PMID- 28422643
TI - Occupational Therapy Interventions for Adults With Traumatic Brain Injury.
AB - This Evidence Connection describes a case report of an adult with traumatic brain
injury (TBI), applying the evidence for intervention from the systematic reviews
on TBI that were conducted in conjunction with the American Occupational Therapy
Association's (AOTA's) Evidence-Based Practice Project. The occupational therapy
assessment and treatment processes for hospital, home, and community settings are
described. Evidence Connection articles provide a clinical application of
systematic reviews developed in conjunction with AOTA's Evidence-Based Practice
Project.
PMID- 28422644
TI - Vision 2025.
PMID- 28422647
TI - EEG-Based Affect and Workload Recognition in a Virtual Driving Environment for
ASD Intervention.
AB - OBJECTIVE: To build group-level classification models capable of recognizing
affective states and mental workload of individuals with autism spectrum disorder
(ASD) during driving skill training. METHODS: Twenty adolescents with ASD
participated in a six-session virtual reality driving simulator-based experiment,
during which their electroencephalogram (EEG) data were recorded alongside
driving events and a therapist's rating of their affective states and mental
workload. Five feature generation approaches including statistical features,
fractal dimension features, higher order crossings (HOC)-based features, power
features from frequency bands, and power features from bins () were applied to
extract relevant features. Individual differences were removed with a two-step
feature calibration method. Finally, binary classification results based on the k
nearest neighbors algorithm and univariate feature selection method were
evaluated by leave-one-subject-out nested cross-validation to compare feature
types and identify discriminative features. RESULTS: The best classification
results were achieved using power features from bins for engagement (0.95) and
boredom (0.78), and HOC-based features for enjoyment (0.90), frustration (0.88),
and workload (0.86). CONCLUSION: Offline EEG-based group-level classification
models are feasible for recognizing binary low and high intensity of affect and
workload of individuals with ASD in the context of driving. However, while
promising the applicability of the models in an online adaptive driving task
requires further development. SIGNIFICANCE: The developed models provide a basis
for an EEG-based passive brain computer interface system that has the potential
to benefit individuals with ASD with an affect- and workload-based individualized
driving skill training intervention.
PMID- 28422646
TI - Coordinated control of terminal differentiation and restriction of cellular
plasticity.
AB - The acquisition of a specific cellular identity is usually paralleled by a
restriction of cellular plasticity. Whether and how these two processes are
coordinated is poorly understood. Transcription factors called terminal selectors
activate identity-specific effector genes during neuronal differentiation to
define the structural and functional properties of a neuron. To study restriction
of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of
ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE
1 results in activation of ASE neuron type-specific effector genes. Once cells
differentiate, their plasticity is restricted and ectopic expression of CHE-1 no
longer results in activation of ASE effector genes. In striking contrast, removal
of the respective terminal selectors of other sensory, inter-, or motor neuron
types now enables ectopically expressed CHE-1 to activate its ASE-specific
effector genes, indicating that terminal selectors not only activate effector
gene batteries but also control the restriction of cellular plasticity. Terminal
selectors mediate this restriction at least partially by organizing chromatin.
The chromatin structure of a CHE-1 target locus is less compact in neurons that
lack their resident terminal selector and genetic epistasis studies with H3K9
methyltransferases suggest that this chromatin modification acts downstream of a
terminal selector to restrict plasticity. Taken together, terminal selectors
activate identity-specific genes and make non-identity-defining genes less
accessible, thereby serving as a checkpoint to coordinate identity specification
with restriction of cellular plasticity.
PMID- 28422648
TI - Fast and Stable Signal Deconvolution via Compressible State-Space Models.
AB - OBJECTIVE: Common biological measurements are in the form of noisy convolutions
of signals of interest with possibly unknown and transient blurring kernels.
Examples include EEG and calcium imaging data. Thus, signal deconvolution of
these measurements is crucial in understanding the underlying biological
processes. The objective of this paper is to develop fast and stable solutions
for signal deconvolution from noisy, blurred, and undersampled data, where the
signals are in the form of discrete events distributed in time and space.
METHODS: We introduce compressible state-space models as a framework to model and
estimate such discrete events. These state-space models admit abrupt changes in
the states and have a convergent transition matrix, and are coupled with
compressive linear measurements. We consider a dynamic compressive sensing
optimization problem and develop a fast solution, using two nested expectation
maximization algorithms, to jointly estimate the states as well as their
transition matrices. Under suitable sparsity assumptions on the dynamics, we
prove optimal stability guarantees for the recovery of the states and present a
method for the identification of the underlying discrete events with precise
confidence bounds. RESULTS: We present simulation studies as well as application
to calcium deconvolution and sleep spindle detection, which verify our
theoretical results and show significant improvement over existing techniques.
CONCLUSION: Our results show that by explicitly modeling the dynamics of the
underlying signals, it is possible to construct signal deconvolution solutions
that are scalable, statistically robust, and achieve high temporal resolution.
SIGNIFICANCE: Our proposed methodology provides a framework for modeling and
deconvolution of noisy, blurred, and undersampled measurements in a fast and
stable fashion, with potential application to a wide range of biological data.
PMID- 28422649
TI - Visual Servoed Three-Dimensional Rotation Control in Zebrafish Larva Heart
Microinjection System.
AB - OBJECTIVE: Zebrafish larva heart microinjection is a widely used technique in
cardiac disease study. Compared with intensively researched rotation control of
spherical or nearly spherical targets with clear structures, such as cells and
embryos, 3-D rotation control of zebrafish larva demands new techniques due to
its nontransparent structures and irregular outlines. METHODS: In this paper, we
present a vision-servo system to automate the rotation process of zebrafish larva
body. A switched control strategy is adopted to rotate zebrafish larva about the
optical axis by using two micropipettes. Precisely rolling about larva body is
performed, which involves a custom-designed rotational micromanipulator. A vision
detection and online tracking algorithm is also developed to meet the requirement
of visual servoing. With designed rotation control strategy, zebrafish larva
heart can be adjusted to a desired orientation, which is often towards the
injection pipette tip. RESULTS: Experimental results show that the designed
system is capable of achieving high success rate of 94% about -axis rotation and
100% about -axis with 50 trails. The system also performs an average speed of 44
s/larva with a satisfied rotation accuracy of 0.5 in the horizontal plane and 2.5
about its roll axis. CONCLUSION: The proposed strategy is effective in flexibly
manipulating larvae in 3-D. SIGNIFICANCE: The developed 3-D rotation control
scheme is able to be applied to injection of various organs in zebrafish larva
body for different experimental requirements.
PMID- 28422650
TI - Joint Magnetic Calibration and Localization Based on Expectation Maximization for
Tongue Tracking.
AB - BACKGROUND: Tongue tracking, which helps researchers gain valuable insights into
speech mechanism, has many applications in speech therapy and language learning.
The wireless localization technique, which involves tracking a small magnetic
tracer within the 3-D oral space, provides a low cost and convenient approach to
capture tongue kinematics. In practice, this technique requires accurate
calibration of three-axial magnetic sensors used in the tracking system. The data
driven calibration depends on the trajectories of magnetic tracer and the ambient
noise, which may change across time and space. METHODS: In this paper, we model
the kinematics of tracer movement and the noisy magnetic measurements in a
Bayesian framework, then present a joint calibration and localization (JCL)
algorithm based on expectation maximization (EM), where the unscented Rauch-Tung
Striebel smoother is employed for tracer localization and the curvilinear search
algorithm is applied for sensor calibration. RESULTS: Based on measurements
conducted on our tongue tracking system with a small magnetic tracer (diameter:
6.05 mm, thickness: 1.25 mm, residual induction: 14 800 G), the JCL algorithm
achieves averaged root mean square error of 0.45 mm for tracer position
estimation and for tracer orientation estimation, which are significantly lower
than those of the separate calibration and localization algorithms. CONCLUSION:
These results show that JCL can help improve the localization accuracy of this
system. SIGNIFICANCE: A potentially high precision tongue tracking method is
demonstrated.
PMID- 28422651
TI - Direct Sparse Odometry.
AB - Direct Sparse Odometry (DSO) is a visual odometry method based on a novel, highly
accurate sparse and direct structure and motion formulation. It combines a fully
direct probabilistic model (minimizing a photometric error) with consistent,
joint optimization of all model parameters, including geometry-represented as
inverse depth in a reference frame-and camera motion. This is achieved in real
time by omitting the smoothness prior used in other direct methods and instead
sampling pixels evenly throughout the images. Since our method does not depend on
keypoint detectors or descriptors, it can naturally sample pixels from across all
image regions that have intensity gradient, including edges or smooth intensity
variations on essentially featureless walls. The proposed model integrates a full
photometric calibration, accounting for exposure time, lens vignetting, and non
linear response functions. We thoroughly evaluate our method on three different
datasets comprising several hours of video. The experiments show that the
presented approach significantly outperforms state-of-the-art direct and indirect
methods in a variety of real-world settings, both in terms of tracking accuracy
and robustness.
PMID- 28422652
TI - Robust Relative Rotation Averaging.
AB - This paper addresses the problem of robust and efficient relative rotation
averaging in the context of large-scale Structure from Motion. Relative rotation
averaging finds global or absolute rotations for a set of cameras from a set of
observed relative rotations between pairs of cameras. We propose a generalized
framework of relative rotation averaging that can use different robust loss
functions and jointly optimizes for all the unknown camera rotations. Our method
uses a quasi-Newton optimization which results in an efficient iteratively
reweighted least squares (IRLS) formulation that works in the Lie algebra of the
3D rotation group. We demonstrate the performance of our approach on a number of
large-scale data sets. We show that our method outperforms existing methods in
the literature both in terms of speed and accuracy.
PMID- 28422653
TI - Learning Compositional Sparse Bimodal Models.
AB - Various perceptual domains have underlying compositional semantics that are
rarely captured in current models. We suspect this is because directly learning
the compositional structure has evaded these models. Yet, the compositional
structure of a given domain can be grounded in a separate domain thereby
simplifying its learning. To that end, we propose a new approach to modeling
bimodal perceptual domains that explicitly relates distinct projections across
each modality and then jointly learns a bimodal sparse representation. The
resulting model enables compositionality across these distinct projections and
hence can generalize to unobserved percepts spanned by this compositional basis.
For example, our model can be trained on red triangles and blue squares; yet,
implicitly will also have learned red squares and blue triangles. The structure
of the projections and hence the compositional basis is learned automatically; no
assumption is made on the ordering of the compositional elements in either
modality. Although our modeling paradigm is general, we explicitly focus on a
tabletop building-blocks setting. To test our model, we have acquired a new
bimodal dataset comprising images and spoken utterances of colored shapes
(blocks) in the tabletop setting. Our experiments demonstrate the benefits of
explicitly leveraging compositionality in both quantitative and human evaluation
studies.
PMID- 28422654
TI - Novel MRI Technique Enables Non-Invasive Measurement of Atrial Wall Thickness.
AB - Knowledge of atrial wall thickness (AWT) has the potential to provide important
information for patient stratification and the planning of interventions in
atrial arrhythmias. To date, information about AWT has only been acquired in post
mortem or poor-contrast computed tomography (CT) studies, providing limited
coverage and highly variable estimates of AWT. We present a novel contrast agent
free MRI sequence for imaging AWT and use it to create personalized AWT maps and
a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol
was used to image ten volunteers and, as proof of concept, two atrial
fibrillation patients. Both atria were manually segmented to create subject
specific AWT maps using an average of nearest neighbors approach. These were then
registered non-linearly to generate an AWT atlas. AWT was 2.4 +/- 0.7 and 2.7 +/-
0.7 mm in the left and right atria, respectively, in good agreement with post
mortem and CT data, where available. AWT was 2.6 +/- 0.7 mm in the left atrium of
a patient without structural heart disease, similar to that of volunteers. In a
patient with structural heart disease, the AWT was increased to 3.1 +/- 1.3 mm.
We successfully designed an MRI protocol to non-invasively measure AWT and create
the first whole-atria AWT atlas. The atlas can be used as a reference to study
alterations in thickness caused by atrial pathology. The protocol can be used to
acquire personalized AWT maps in a clinical setting and assist in the treatment
of atrial arrhythmias.
PMID- 28422655
TI - Validation of a Regression Technique for Segmentation of White Matter
Hyperintensities in Alzheimer's Disease.
AB - Segmentation and volumetric quantification of white matter hyperintensities
(WMHs) is essential in assessment and monitoring of the vascular burden in aging
and Alzheimer's disease (AD), especially when considering their effect on
cognition. Manually segmenting WMHs in large cohorts is technically unfeasible
due to time and accuracy concerns. Automated tools that can detect WMHs robustly
and with high accuracy are needed. Here, we present and validate a fully
automatic technique for segmentation and volumetric quantification of WMHs in
aging and AD. The proposed technique combines intensity and location features
frommultiplemagnetic resonance imaging contrasts and manually labeled training
data with a linear classifier to perform fast and robust segmentations. It
provides both a continuous subject specific WMH map reflecting different levels
of tissue damage and binary segmentations. Themethodwas used to detectWMHs in 80
elderly/AD brains (ADC data set) as well as 40 healthy subjects at risk of AD
(PREVENT-AD data set). Robustness across different scanners was validated using
ten subjects from ADNI2/GO study. Voxel-wise and volumetric agreements were
evaluated using Dice similarity index (SI) and intra-class correlation (ICC),
yielding ICC=0.96 , SI = 0.62+/-0.16 for ADC data set and ICC=0.78 , SI=0.51+/
0.15 for PREVENT-AD data set. The proposed method was robust in the independent
sample yielding SI=0.64+/-0.17 with ICC=0.93 for ADNI2/GO subjects. The proposed
method provides fast, accurate, and robust segmentations on previously unseen
data from different models of scanners, making it ideal to study WMHs in large
scale multi-site studies.
PMID- 28422656
TI - Fast Plane Wave 2-D Vector Flow Imaging Using Transverse Oscillation and
Directional Beamforming.
AB - Several techniques can estimate the 2-D velocity vector in ultrasound.
Directional beamforming (DB) estimates blood flow velocities with a higher
precision and accuracy than transverse oscillation (TO), but at the cost of a
high beamforming load when estimating the flow angle. In this paper, it is
proposed to use TO to estimate an initial flow angle, which is then refined in a
DB step. Velocity magnitude is estimated along the flow direction using cross
correlation. It is shown that the suggested TO-DB method can improve the
performance of velocity estimates compared with TO, and with a beamforming load,
which is 4.6 times larger than for TO and seven times smaller than for
conventional DB. Steered plane wave transmissions are employed for high frame
rate imaging, and parabolic flow with a peak velocity of 0.5 m/s is simulated in
straight vessels at beam-to-flow angles from 45 degrees to 90 degrees . The TO
DB method estimates the angle with a bias and standard deviation (SD) less than 2
degrees , and the SD of the velocity magnitude is less than 2%. When using only
TO, the SD of the angle ranges from 2 degrees to 17 degrees and for the
velocity magnitude up to 7%. Bias of the velocity magnitude is within 2% for TO
and slightly larger but within 4% for TO-DB. The same trends are observed in
measurements although with a slightly larger bias. Simulations of realistic flow
in a carotid bifurcation model provide visualization of complex flow, and the
spread of velocity magnitude estimates is 7.1 cm/s for TO-DB, while it is 11.8
cm/s using only TO. However, velocities for TO-DB are underestimated at peak
systole as indicated by a regression value of 0.97 for TO and 0.85 for TO-DB. An
in vivo scanning of the carotid bifurcation is used for vector velocity
estimations using TO and TO-DB. The SD of the velocity profile over a cardiac
cycle is 4.2% for TO and 3.2% for TO-DB.
PMID- 28422657
TI - Phased Array Ultrasound System for Planar Flow Mapping in Liquid Metals.
AB - Controllable magnetic fields can be used to optimize flows in technical and
industrial processes involving liquid metals in order to improve quality and
yield. However, experimental studies in magnetohydrodynamics often involve
complex, turbulent flows and require planar, two-component (2c) velocity
measurements through only one acoustical access. We present the phased array
ultrasound Doppler velocimeter as a modular research platform for flow mapping in
liquid metals. It combines the pulse wave Doppler method with the phased array
technique to adaptively focus the ultrasound beam. This makes it possible to
resolve smaller flow structures in planar measurements compared with fixed-beam
sensors and enables 2c flow mapping with only one acoustical access via the cross
beam technique. From simultaneously measured 2-D velocity fields, quantities for
turbulence characterization can be derived. The capabilities of this measurement
system are demonstrated through measurements in the alloy gallium-indium-tin at
room temperature. The 2-D, 2c velocity measurements of a flow in a cubic vessel
driven by a rotating magnetic field (RMF) with a spatial resolution of up to 2.2
mm are presented. The measurement results are in good agreement with a
semianalytical simulation. As a highlight, two-point correlation functions of the
velocity field for different magnitudes of the RMF are presented.
PMID- 28422658
TI - Equivalent Magnetic Noise in Magnetoelectric Laminates Comprising Bidomain LiNbO3
Crystals.
AB - The anisotropic direct magnetoelectric (ME) properties of bilayered composites
comprising magnetostrictive metglas foils and single-crystalline piezoelectric
bidomain plates of 127 degrees Y-cut LiNbO3 (LNO) have been studied theoretically
and experimentally. The LNO plates possessed an engineered ferroelectric
macrobidomain structure with opposite spontaneous polarization vectors.
Impedance, ME effect, and equivalent magnetic noise density (EMND) measurements
have been performed under quasi-static and resonant conditions. Whereas the quasi
static ME effect was only two times stronger in the bidomain samples compared to
their unidomain and bonded bimorph counterparts, in the bending resonance mode,
the effect was up to one order of magnitude stronger: ME coefficients of up to
578 V/( [Formula: see text]) were obtained at ca. 30 kHz under resonance using
0.5-mm-thick crystals. EMND measurements yielded values down to 153 pT/Hz 1/2 at
1 kHz and 524 fT/Hz 1/2 under resonant conditions. A further optimization of the
fabrication techniques, laminate geometry, and detection circuit is expected to
allow reducing these values down to at least 10 pT/Hz 1/2 and 250 fT/Hz 1/2 ,
respectively, and the resonance frequency by at least two orders of magnitude.
Such systems may thus find use in simple and sensitive, passive and stable, low
frequency and high-temperature vector magnetic field sensors.
PMID- 28422659
TI - Revisiting Co-Saliency Detection: A Novel Approach Based on Two-Stage Multi-View
Spectral Rotation Co-clustering.
AB - With the goal of discovering the common and salient objects from the given image
group, co-saliency detection has received tremendous research interest in recent
years. However, as most of the existing co-saliency detection methods are
performed based on the assumption that all the images in the given image group
should contain co-salient objects in only one category, they can hardly be
applied in practice, particularly for the large-scale image set obtained from the
Internet. To address this problem, this paper revisits the co-saliency detection
task and advances its development into a new phase, where the problem setting is
generalized to allow the image group to contain objects in arbitrary number of
categories and the algorithms need to simultaneously detect multi-class co
salient objects from such complex data. To solve this new challenge, we decompose
it into two sub-problems, i.e., how to identify subgroups of relevant images and
how to discover relevant co-salient objects from each subgroup, and propose a
novel co-saliency detection framework to correspondingly address the two sub
problems via two-stage multi-view spectral rotation co-clustering. Comprehensive
experiments on two publically available benchmarks demonstrate the effectiveness
of the proposed approach. Notably, it can even outperform the state-of-the-art co
saliency detection methods, which are performed based on the image subgroups
carefully separated by the human labor.
PMID- 28422660
TI - Weak Classifier for Density Estimation in Eye Localization and Tracking.
AB - In this paper, we propose a fast weak classifier that can detect and track eyes
in video sequences. The approach relies on a least-squares detector based on the
inner product detector (IPD) that can stimate a probability density distribution
for a feature's location-which fits naturally with a Bayesian estimation cycle,
such as a Kalman or particle filter. As a least-squares sliding window detector,
it possesses tolerance to small variations in the desired pattern while
maintaining good generalization capabilities and computational efficiency. We
propose two approaches to integrating the IPD with a particle filter tracker. We
use the BioID, FERET, LFPW, and COFW public datasets as well as five manually
annotated high-definition video sequences to quantitatively evaluate the
algorithms' performance. The video data set contains four subjects, different
types of backgrounds, blurring due to fast motion, and occlusions. All code and
data are available.
PMID- 28422661
TI - Correlated Topic Vector for Scene Classification.
AB - Scene images usually involve semantic correlations, particularly when considering
large-scale image data sets. This paper proposes a novel generative image
representation, correlated topic vector, to model such semantic correlations.
Oriented from the correlated topic model, correlated topic vector intends to
naturally utilize the correlations among topics, which are seldom considered in
the conventional feature encoding, e.g., Fisher vector, but do exist in scene
images. It is expected that the involvement of correlations can increase the
discriminative capability of the learned generative model and consequently
improve the recognition accuracy. Incorporated with the Fisher kernel method,
correlated topic vector inherits the advantages of Fisher vector. The
contributions to the topics of visual words have been further employed by
incorporating the Fisher kernel framework to indicate the differences among
scenes. Combined with the deep convolutional neural network (CNN) features and
Gibbs sampling solution, correlated topic vector shows great potential when
processing large-scale and complex scene image data sets. Experiments on two
scene image data sets demonstrate that correlated topic vector improves
significantly the deep CNN features, and outperforms existing Fisher kernel-based
features.
PMID- 28422662
TI - Use of Accelerometers in the Control of Practical Prosthetic Arms.
AB - Accelerometers can be used to augment the control of powered prosthetic arms.
They can detect the orientation of the joint and limb, and the controller can
correct for the amount of torque required to move the limb. They can also be used
to create a platform, with a fixed orientation relative to gravity for the object
held in the hand. This paper describes three applications for this technology, in
a powered wrist and powered arm. By adding sensors to the arm making these data
available to the controller, the input from the user can be made simpler. The
operator will not need to correct for changes in orientation of their body as
they move. Two examples of the correction for orientation against gravity are
described and an example of the system designed for use by a patient. The
controller for all examples is a distributed set of microcontrollers, one node
for each joint, linked with the control area network bus. The clinical arm uses a
version of the Southampton adaptive manipulation scheme to control the arm and
hand. In this control form, the user gives simpler input commands and leaves the
detailed control of the arm to the controller.
PMID- 28422663
TI - A Neural Probe With Up to 966 Electrodes and Up to 384 Configurable Channels in
0.13 $?mu$m SOI CMOS.
AB - In vivo recording of neural action-potential and local-field-potential signals
requires the use of high-resolution penetrating probes. Several international
initiatives to better understand the brain are driving technology efforts towards
maximizing the number of recording sites while minimizing the neural probe
dimensions. We designed and fabricated (0.13- MUm SOI Al CMOS) a 384-channel
configurable neural probe for large-scale in vivo recording of neural signals. Up
to 966 selectable active electrodes were integrated along an implantable shank
(70 MUm wide, 10 mm long, 20 MUm thick), achieving a crosstalk of [Formula: see
text] dB. The probe base (5 * 9 mm 2 ) implements dual-band recording and a 171.6
Mbps digital interface. Measurement results show a total input-referred noise of
6.4 MU V rms and a total power consumption of 49.1 MUW/channel.
PMID- 28422664
TI - Diaper-Embedded Urinary Tract Infection Monitoring Sensor Module Powered by Urine
Activated Batteries.
AB - Urinary tract infection (UTI) is one of the most common infections in humans. UTI
is easily treatable using antibiotics if identified in early stage. However,
without early identification and treatment, UTI can be a major source of serious
complications in geriatric patients, in particular, those suffering from
neurodegenerative diseases. Also, for infants who have difficulty in describing
their symptoms, UTI may lead to serious development of the disease making early
identification of UTI crucial. In this paper, we present a diaper-embedded,
wireless, self-powered, and autonomous UTI monitoring sensor module that allows
an early detection of UTI with minimal effort. The sensor module consists of a
paper-based colorimetric nitrite sensor, urine-activated batteries, a boost dc-dc
converter, a low-power sensor interface utilizing pulse width modulation, and a
Bluetooth low energy module for wireless transmission. Experimental results show
a better detection of nitrite, a surrogate of UTI, than that of conventional
dipstick testing. The proposed sensor module achieves a sensitivity of 1.35
ms/(mg/L) and a detection limit of 4 mg/L for nitrite.
PMID- 28422665
TI - Human Factors and Neurophysiological Metrics in Air Traffic Control: A Critical
Review.
AB - This paper provides a focused and organized review of the research progress on
neurophysiological indicators, also called "neurometrics," to show how they can
effectively address some of the most important human factors (HFs) needs in the
air traffic management (ATM) field. In order to better understand and highlight
available opportunities of such neuroscientific applications, state of the art on
the most involved HFs and related cognitive processes (e.g., mental workload and
cognitive training) are presented together with examples of possible applications
in current and future ATM scenarios. Furthermore, this paper will discuss the
potential enhancements that further research and development activities could
bring to the efficiency and safety of the ATM service.
PMID- 28422666
TI - Efficient kNN Classification With Different Numbers of Nearest Neighbors.
AB - nearest neighbor (kNN) method is a popular classification method in data mining
and statistics because of its simple implementation and significant
classification performance. However, it is impractical for traditional kNN
methods to assign a fixed value (even though set by experts) to all test samples.
Previous solutions assign different values to different test samples by the cross
validation method but are usually time-consuming. This paper proposes a kTree
method to learn different optimal values for different test/new samples, by
involving a training stage in the kNN classification. Specifically, in the
training stage, kTree method first learns optimal values for all training samples
by a new sparse reconstruction model, and then constructs a decision tree
(namely, kTree) using training samples and the learned optimal values. In the
test stage, the kTree fast outputs the optimal value for each test sample, and
then, the kNN classification can be conducted using the learned optimal value and
all training samples. As a result, the proposed kTree method has a similar
running cost but higher classification accuracy, compared with traditional kNN
methods, which assign a fixed value to all test samples. Moreover, the proposed
kTree method needs less running cost but achieves similar classification
accuracy, compared with the newly kNN methods, which assign different values to
different test samples. This paper further proposes an improvement version of
kTree method (namely, k*Tree method) to speed its test stage by extra storing the
information of the training samples in the leaf nodes of kTree, such as the
training samples located in the leaf nodes, their kNNs, and the nearest neighbor
of these kNNs. We call the resulting decision tree as k*Tree, which enables to
conduct kNN classification using a subset of the training samples in the leaf
nodes rather than all training samples used in the newly kNN methods. This
actually reduces running cost of test stage. Finally, the experimental results on
20 real data sets showed that our proposed methods (i.e., kTree and k*Tree) are
much more efficient than the compared methods in terms of classification tasks.
PMID- 28422667
TI - Modeling and Analysis of Beta Oscillations in the Basal Ganglia.
AB - Enhanced beta (12-30 Hz) oscillatory activity in the basal ganglia (BG) is a
prominent feature of the Parkinsonian state in animal models and in patients with
Parkinson's disease. Increased beta oscillations are associated with severe
dopaminergic striatal depletion. However, the mechanisms underlying these
pathological beta oscillations remain elusive. Inspired by the experimental
observation that only subsets of neurons within each nucleus in the BG exhibit
oscillatory activities, a computational model of the BG-thalamus neuronal network
is proposed, which is characterized by subdivided nuclei within the BG. Using
different currents externally applied to the neurons within a given nucleus,
neurons behave according to one of the two subgroups, named "-N" and "-P," where
"-N" and "-P" denote the normal and the Parkinsonian states, respectively. The
ratio of "-P" to "-N" neurons indicates the degree of the Parkinsonian state.
Simulation results show that if "-P" neurons have a high degree of connectivity
in the subthalamic nucleus (STN), they will have a significant downstream effect
on the generation of beta oscillations in the globus pallidus. Interestingly,
however, the generation of beta oscillations in the STN is independent of the
selection of the "-P" neurons in the external segment of the globus pallidus
(GPe), despite the reciprocal structure between STN and GPe. This computational
model may pave the way to revealing the mechanism of such pathological behaviors
in a realistic way that can replicate experimental observations. The simulation
results suggest that the STN is more suitable than GPe as a deep brain
stimulation target.
PMID- 28422668
TI - Sensitivity Analysis for Probabilistic Neural Network Structure Reduction.
AB - In this paper, we propose the use of local sensitivity analysis (LSA) for the
structure simplification of the probabilistic neural network (PNN). Three
algorithms are introduced. The first algorithm applies LSA to the PNN input layer
reduction by selecting significant features of input patterns. The second
algorithm utilizes LSA to remove redundant pattern neurons of the network. The
third algorithm combines the proposed two and constitutes the solution of how
they can work together. PNN with a product kernel estimator is used, where each
multiplicand computes a one-dimensional Cauchy function. Therefore, the smoothing
parameter is separately calculated for each dimension by means of the plug-in
method. The classification qualities of the reduced and full structure PNN are
compared. Furthermore, we evaluate the performance of PNN, for which global
sensitivity analysis (GSA) and the common reduction methods are applied, both in
the input layer and the pattern layer. The models are tested on the
classification problems of eight repository data sets. A 10-fold cross validation
procedure is used to determine the prediction ability of the networks. Based on
the obtained results, it is shown that the LSA can be used as an alternative PNN
reduction approach.
PMID- 28422669
TI - Bioinspired Approach to Modeling Retinal Ganglion Cells Using System
Identification Techniques.
AB - The processing capabilities of biological vision systems are still vastly
superior to artificial vision, even though this has been an active area of
research for over half a century. Current artificial vision techniques integrate
many insights from biology yet they remain far-off the capabilities of animals
and humans in terms of speed, power, and performance. A key aspect to modeling
the human visual system is the ability to accurately model the behavior and
computation within the retina. In particular, we focus on modeling the retinal
ganglion cells (RGCs) as they convey the accumulated data of real world images as
action potentials onto the visual cortex via the optic nerve. Computational
models that approximate the processing that occurs within RGCs can be derived by
quantitatively fitting the sets of physiological data using an input-output
analysis where the input is a known stimulus and the output is neuronal
recordings. Currently, these input-output responses are modeled using
computational combinations of linear and nonlinear models that are generally
complex and lack any relevance to the underlying biophysics. In this paper, we
illustrate how system identification techniques, which take inspiration from
biological systems, can accurately model retinal ganglion cell behavior, and are
a viable alternative to traditional linear-nonlinear approaches.
PMID- 28422670
TI - Observer-Based Robust Coordinated Control of Multiagent Systems With Input
Saturation.
AB - This paper addresses the robust semiglobal coordinated control of multiple-input
multiple-output multiagent systems with input saturation together with dead zone
and input additive disturbance. Observer-based coordinated control protocol is
constructed, by combining the parameterized low-and-high-gain feedback technique
and the high-gain observer design approach. It is shown that, under some mild
assumptions on agents' intrinsic dynamics, the robust semiglobal consensus or
robust semiglobal swarm can be approached for undirected connected multiagent
systems. Then, specific guidelines on the selection of the low-gain parameter,
the high-gain parameter, and the high-gain observer gain have been provided. At
last, numerical simulations are presented to illustrate the theoretical results.
PMID- 28422671
TI - Structured Learning of Tree Potentials in CRF for Image Segmentation.
AB - We propose a new approach to image segmentation, which exploits the advantages of
both conditional random fields (CRFs) and decision trees. In the literature, the
potential functions of CRFs are mostly defined as a linear combination of some
predefined parametric models, and then, methods, such as structured support
vector machines, are applied to learn those linear coefficients. We instead
formulate the unary and pairwise potentials as nonparametric forests-ensembles of
decision trees, and learn the ensemble parameters and the trees in a unified
optimization problem within the large-margin framework. In this fashion, we
easily achieve nonlinear learning of potential functions on both unary and
pairwise terms in CRFs. Moreover, we learn classwise decision trees for each
object that appears in the image. Experimental results on several public
segmentation data sets demonstrate the power of the learned nonlinear
nonparametric potentials.
PMID- 28422672
TI - AIIMDs: An Integrated Framework of Automatic Idiopathic Inflammatory Myopathy
Diagnosis for Muscle.
AB - Idiopathic inflammatory myopathy (IIM) is a common skeletal muscle disease that
relates to weakness and inflammation of muscle. Early diagnosis and prognosis of
different types of IIMs will guide the effective treatment. Interpretation of
digitized images of the cross-section muscle biopsy, which is currently done
manually, provides the most reliable diagnostic information. With the increasing
volume of images, the management and manual interpretation of the digitized
muscle images suffer from low efficiency and high interobserver variabilities. In
order to address these problems, we propose the first complete framework of
automatic IIM diagnosis system for the management and interpretation of digitized
skeletal muscle histopathology images. The proposed framework consists of several
key components: (1) Automatic cell segmentation, perimysium annotation, and
nuclei detection; (2) histogram-based feature extraction and quantification; (3)
content-based image retrieval to search and retrieve similar cases in the
database for comparative study; and (4) majority voting-based classification to
provide decision support for computer-aided clinical diagnosis. Experiments show
that the proposed diagnosis system provides efficient and robust interpretation
of the digitized muscle image and computer-aided diagnosis of IIM.
PMID- 28422673
TI - A Two-Phase Evolutionary Approach for Compressive Sensing Reconstruction.
AB - Sparse signal reconstruction can be regarded as a problem of locating the nonzero
entries of the signal. In presence of measurement noise, conventional methods
such as l1 norm relaxation methods and greedy algorithms, have shown their
weakness in finding the nonzero entries accurately. In order to reduce the impact
of noise and better locate the nonzero entries, in this paper, we propose a two
phase algorithm which works in a coarse-to-fine manner. In phase 1, a
decomposition-based multiobjective evolutionary algorithm is applied to generate
a group of robust solutions by optimizing l1 norm of the solutions. To remove the
interruption of noise, the statistical features with respect to each entry among
these solutions are extracted and an initial set of nonzero entries are
determined by clustering technique. In phase 2, a forward-based selection method
is proposed to further update this set and locate the nonzero entries more
precisely based on these features. At last, the magnitudes of the reconstructed
signal are obtained by the method of least squares. We conduct the comparison of
our proposed method with several state-of-the-art compressive sensing recover
methods, the best result in phase 1 and the approach combining phases 1 and 2
without the statistical features. Experimental results on benchmark signals as
well as randomly generated signals demonstrate that our proposed method
outperforms the above methods, achieving higher recover precision and maintaining
larger sparsity.
PMID- 28422674
TI - Incorporation of Efficient Second-Order Solvers Into Latent Factor Models for
Accurate Prediction of Missing QoS Data.
AB - Generating highly accurate predictions for missing quality-of-service (QoS) data
is an important issue. Latent factor (LF)-based QoS-predictors have proven to be
effective in dealing with it. However, they are based on first-order solvers that
cannot well address their target problem that is inherently bilinear and
nonconvex, thereby leaving a significant opportunity for accuracy improvement.
This paper proposes to incorporate an efficient second-order solver into them to
raise their accuracy. To do so, we adopt the principle of Hessian-free
optimization and successfully avoid the direct manipulation of a Hessian matrix,
by employing the efficiently obtainable product between its Gauss-Newton
approximation and an arbitrary vector. Thus, the second-order information is
innovatively integrated into them. Experimental results on two industrial QoS
datasets indicate that compared with the state-of-the-art predictors, the newly
proposed one achieves significantly higher prediction accuracy at the expense of
affordable computational burden. Hence, it is especially suitable for industrial
applications requiring high prediction accuracy of unknown QoS data.
PMID- 28422675
TI - Finite-Time Synchronization of Coupled Hierarchical Hybrid Neural Networks With
Time-Varying Delays.
AB - This paper is concerned with the finite-time synchronization problem of coupled
hierarchical hybrid delayed neural networks. This coupled hierarchical hybrid
neural networks consist of a higher level switching and a lower level Markovian
jumping. The time-varying delays are dependent on not only switching signal but
also jumping mode. By using a less conservative weighted integral inequality and
stochastic multiple Lyapunov-Krasovskii functional, new finite-time
synchronization criteria are obtained, which makes the state trajectories be kept
within the prescribed bound in a time interval. Finally, an example is proposed
to demonstrate the effectiveness of the obtained results.
PMID- 28422676
TI - Supervised and Unsupervised Aspect Category Detection for Sentiment Analysis with
Co-occurrence Data.
AB - Using online consumer reviews as electronic word of mouth to assist purchase
decision making has become increasingly popular. The Web provides an extensive
source of consumer reviews, but one can hardly read all reviews to obtain a fair
evaluation of a product or service. A text processing framework that can
summarize reviews, would therefore be desirable. A subtask to be performed by
such a framework would be to find the general aspect categories addressed in
review sentences, for which this paper presents two methods. In contrast to most
existing approaches, the first method presented is an unsupervised method that
applies association rule mining on co-occurrence frequency data obtained from a
corpus to find these aspect categories. While not on par with state-of-the-art
supervised methods, the proposed unsupervised method performs better than several
simple baselines, a similar but supervised method, and a supervised baseline,
with an -score of 67%. The second method is a supervised variant that outperforms
existing methods with an -score of 84%.
PMID- 28422677
TI - Learning Sparse Representation for Objective Image Retargeting Quality
Assessment.
AB - The goal of image retargeting is to adapt source images to target displays with
different sizes and aspect ratios. Different retargeting operators create
different retargeted images, and a key problem is to evaluate the performance of
each retargeting operator. Subjective evaluation is most reliable, but it is
cumbersome and labor-consuming, and more importantly, it is hard to be embedded
into online optimization systems. This paper focuses on exploring the
effectiveness of sparse representation for objective image retargeting quality
assessment. The principle idea is to extract distortion sensitive features from
one image (e.g., retargeted image) and further investigate how many of these
features are preserved or changed in another one (e.g., source image) to measure
the perceptual similarity between them. To create a compact and robust feature
representation, we learn two overcomplete dictionaries to represent the
distortion sensitive features of an image. Features including local geometric
structure and global context information are both addressed in the proposed
framework. The intrinsic discriminative power of sparse representation is then
exploited to measure the similarity between the source and retargeted images.
Finally, individual quality scores are fused into an overall quality by a typical
regression method. Experimental results on several databases have demonstrated
the superiority of the proposed method.
PMID- 28422678
TI - Correlation Filter Learning Toward Peak Strength for Visual Tracking.
AB - This paper presents a novel visual tracking approach to correlation filter
learning toward peak strength of correlation response. Previous methods leverage
all features of the target and the immediate background to learn a correlation
filter. Some features, however, may be distractive to tracking, like those from
occlusion and local deformation, resulting in unstable tracking performance. This
paper aims at solving this issue and proposes a novel algorithm to learn the
correlation filter. The proposed approach, by imposing an elastic net constraint
on the filter, can adaptively eliminate those distractive features in the
correlation filtering. A new peak strength metric is proposed to measure the
discriminative capability of the learned correlation filter. It is demonstrated
that the proposed approach effectively strengthens the peak of the correlation
response, leading to more discriminative performance than previous methods.
Extensive experiments on a challenging visual tracking benchmark demonstrate that
the proposed tracker outperforms most state-of-the-art methods.
PMID- 28422679
TI - A Bio-Inspired Approach to Traffic Network Equilibrium Assignment Problem.
AB - Finding an equilibrium state of the traffic assignment plays a significant role
in the design of transportation networks. We adapt the path finding mathematical
model of slime mold Physarum polycephalum to solve the traffic equilibrium
assignment problem. We make three contributions in this paper. First, we propose
a generalized Physarum model to solve the shortest path problem in directed and
asymmetric graphs. Second, we extend it further to resolve the network design
problem with multiple source nodes and sink nodes. At last, we demonstrate that
the Physarum solver converges to the user-optimized (Wardrop) equilibrium by
dynamically updating the costs of links in the network. In addition, convergence
of the developed algorithm is proved. Numerical examples are used to demonstrate
the efficiency of the proposed algorithm. The superiority of the proposed
algorithm is demonstrated in comparison with several other algorithms, including
the Frank-Wolfe algorithm, conjugate Frank-Wolfe algorithm, biconjugate Frank
Wolfe algorithm, and gradient projection algorithm.
PMID- 28422680
TI - A Unified Framework for Tracking Based Text Detection and Recognition from Web
Videos.
AB - Video text extraction plays an important role for multimedia understanding and
retrieval. Most previous research efforts are conducted within individual frames.
A few of recent methods, which pay attention to text tracking using multiple
frames, however, do not effectively mine the relations among text detection,
tracking and recognition. In this paper, we propose a generic Bayesian-based
framework of Tracking based Text Detection And Recognition (T DAR) from web
videos for embedded captions, which is composed of three major components, i.e.,
text tracking, tracking based text detection, and tracking based text
recognition. In this unified framework, text tracking is first conducted by
tracking-by-detection. Tracking trajectories are then revised and refined with
detection or recognition results. Text detection or recognition is finally
improved with multi-frame integration. Moreover, a challenging video text
(embedded caption text) database (USTB-VidTEXT) is constructed and publicly
available. A variety of experiments on this dataset verify that our proposed
approach largely improves the performance of text detection and recognition from
web videos.
PMID- 28422681
TI - Fast Median Filtering for Phase or Orientation Data.
AB - Median filtering is among the most utilized tools for smoothing real-valued data,
as it is robust, edge-preserving, value-preserving, and yet can be computed
efficiently. For data living on the unit circle, such as phase data or
orientation data, a filter with similar properties is desirable. For these data,
there is no unique means to define a median; so we discuss various possibilities.
The arc distance median turns out to be the only variant which leads to robust,
edge-preserving and value-preserving smoothing. However, there are no efficient
algorithms for filtering based on the arc distance median. Here, we propose fast
algorithms for filtering of signals and images with values on the unit circle
based on the arc distance median. For non-quantized data, we develop an algorithm
that scales linearly with the filter size. The runtime of our reference
implementation is only moderately higher than the Matlab implementation of the
classical median filter for real-valued data. For quantized data, we obtain an
algorithm of constant complexity w.r.t. the filter size. We demonstrate the
performance of our algorithms for real life data sets: phase images from
interferometric synthetic aperture radar, planar flow fields from optical flow,
and time series of wind directions.
PMID- 28422682
TI - MRI-Based Medial Axis Extraction and Boundary Segmentation of Cranial Nerves
Through Discrete Deformable 3D Contour and Surface Models.
AB - This paper presents a segmentation technique to identify the medial axis and the
boundary of cranial nerves. We utilize a 3-D deformable one-simplex discrete
contour model to extract the medial axis of each cranial nerve. This contour
model represents a collection of two-connected vertices linked by edges, where
vertex position is determined by a Newtonian expression for vertex kinematics
featuring internal and external forces, the latter of which include attractive
forces toward the nerve medial axis. We exploit multiscale vesselness filtering
and minimal path techniques in the medial axis extraction method, which also
computes a radius estimate along the path. Once we have the medial axis and the
radius function of a nerve, we identify the nerve surface using a two-simplex
deformable model, which expands radially and can accommodate any nerve shape. As
a result, the method proposed here combines the benefits of explicit contour and
surface models, while also achieving a cornerstone for future work that will
emphasize shape statistics, static collision with other critical structures, and
tree-shape analysis.
PMID- 28422684
TI - Visual Analysis of Inclusion Dynamics in Two-Phase Flow.
AB - In single-phase flow visualization, research focuses on the analysis of vector
field properties. In two-phase flow, in contrast, analysis of the phase
components is typically of major interest. So far, visualization research of two
phase flow concentrated on proper interface reconstruction and the analysis
thereof. In this paper, we present a novel visualization technique that enables
the investigation of complex two-phase flow phenomena with respect to the physics
of breakup and coalescence of inclusions. On the one hand, we adapt dimensionless
quantities for a localized analysis of phase instability and breakup, and provide
detailed inspection of breakup dynamics with emphasis on oscillation and its
interplay with rotational motion. On the other hand, we present a parametric
tightly linked space-time visualization approach for an effective interactive
representation of the overall dynamics. We demonstrate the utility of our
approach using several two-phase CFD datasets.
PMID- 28422683
TI - Progressive Dictionary Learning With Hierarchical Predictive Structure for Low
Bit-Rate Scalable Video Coding.
AB - Dictionary learning has emerged as a promising alternative to the conventional
hybrid coding framework. However, the rigid structure of sequential training and
prediction degrades its performance in scalable video coding. This paper proposes
a progressive dictionary learning framework with hierarchical predictive
structure for scalable video coding, especially in low bitrate region. For
pyramidal layers, sparse representation based on spatio-temporal dictionary is
adopted to improve the coding efficiency of enhancement layers with a guarantee
of reconstruction performance. The overcomplete dictionary is trained to
adaptively capture local structures along motion trajectories as well as exploit
the correlations between the neighboring layers of resolutions. Furthermore,
progressive dictionary learning is developed to enable the scalability in
temporal domain and restrict the error propagation in a closed-loop predictor.
Under the hierarchical predictive structure, online learning is leveraged to
guarantee the training and prediction performance with an improved convergence
rate. To accommodate with the state-of-the-art scalable extension of H.264/AVC
and latest High Efficiency Video Coding (HEVC), standardized codec cores are
utilized to encode the base and enhancement layers. Experimental results show
that the proposed method outperforms the latest scalable extension of HEVC and
HEVC simulcast over extensive test sequences with various resolutions.
PMID- 28422685
TI - Outdoor Markerless Motion Capture with Sparse Handheld Video Cameras.
AB - We present a method for outdoor markerless motion capture with sparse handheld
video cameras. In the simplest setting, it only involves two mobile phone cameras
following the character. This setup can maximize the flexibilities of data
capture and broaden the applications of motion capture. To solve the character
pose under such challenge settings, we exploit the generative motion capture
methods and propose a novel model-view consistency that considers both foreground
and background in the tracking stage. The background is modeled as a deformable
2D grid, which allows us to compute the background-view consistency for sparse
moving cameras. The 3D character pose is tracked with a global-local optimization
through minimizing our consistency cost. A novel motion regularizer is also
proposed in the optimization to constrain the solution pose space. The whole
process of the proposed method is simple as frame by frame video segmentation is
not required. Our method outperforms several alternative methods on various
examples demonstrated in the paper.
PMID- 28422686
TI - An Integrated Movement Analysis Framework to Study Upper Limb Function: A Pilot
Study.
AB - The functional capabilities of individuals with upper limb disabilities are
assessed throughout rehabilitation and treatment regimens using functional
outcome measures. For the upper limb amputee population, there are none which
quantitatively take into account the quality of movement while an individual is
performing tasks. In this paper, we demonstrate the use of an integrated movement
analysis framework, based on motion capture and ground reaction force data, to
capture quantitative information about how subjects complete a commonly used
functional outcome measure, the Box and Blocks Test (BBT). In order to test the
usefulness of the integrated movement analysis framework in capturing the quality
of movements during task performance, a motion restriction was induced in able
bodied participants that reproduces some of the limitations imposed by
conventional prosthetics. Each subject performed the BBT under normal conditions
and also under the motion restriction condition. The motion capture and ground
force plates captured movement that significantly differed between the two
conditions, with the largest differences seen in shoulder motion, in the range of
motions of head tilt and elbow flexion, and in the area of the center of pressure
trajectory. These preliminary results show the feasibility of incorporating
standardized, quantitative movement analysis into the assessment of function for
those with an upper limb disability.
PMID- 28422688
TI - Person Reidentification Based on Elastic Projections.
AB - Person reidentification usually refers to matching people in different camera
views in nonoverlapping multicamera networks. Many existing methods learn a
similarity measure by projecting the raw feature to a latent subspace to make the
same target's distance smaller than different targets' distances. However, the
same targets captured in different camera views should hold the same intrinsic
attributes while different targets should hold different intrinsic attributes.
Projecting all the data to the same subspace would cause loss of such an
information and comparably poor discriminability. To address this problem, in
this paper, a method based on elastic projections is proposed to learn a pairwise
similarity measure for person reidentification. The proposed model learns two
projections, positive projection and negative projection, which are both
representative and discriminative. The representability refers to: for the same
targets captured in two camera views, the positive projection can bridge the
corresponding appearance variation and represent the intrinsic attributes of the
same targets, while for the different targets captured in two camera views, the
negative projection can explore and utilize the different attributes of different
targets. The discriminability means that the intraclass distance should become
smaller than its original distance after projection, while the interclass
distance becomes larger on the contrary, which is the elastic property of the
proposed model. In this case, prior information of the original data space is
used to give guidance for the learning phase; more importantly, similar targets
(but not the same) are effectively reduced by forcing the same targets to become
more similar and different targets to become more distinct. The proposed model is
evaluated on three benchmark data sets, including VIPeR, GRID, and CUHK, and
achieves better performance than other methods.
PMID- 28422687
TI - Theoretical Limits on Multiuser Molecular Communication in Internet of Nano-Bio
Things.
AB - In nano-bio networks, multiple transmitter-receiver pairs will operate in the
same medium. Both inter-symbol interference and multi-user interference can cause
saturation at the receiver side, and this effect may cause an outage. Thus, we
propose a tractable framework to calculate the theoretical operating points for
fully absorbing receiver.
PMID- 28422689
TI - A Novel Recurrent Neural Network for Manipulator Control With Improved Noise
Tolerance.
AB - In this paper, we propose a novel recurrent neural network to resolve the
redundancy of manipulators for efficient kinematic control in the presence of
noises in a polynomial type. Leveraging the high-order derivative properties of
polynomial noises, a deliberately devised neural network is proposed to eliminate
the impact of noises and recover the accurate tracking of desired trajectories in
workspace. Rigorous analysis shows that the proposed neural law stabilizes the
system dynamics and the position tracking error converges to zero in the presence
of noises. Extensive simulations verify the theoretical results. Numerical
comparisons show that existing dual neural solutions lose stability when exposed
to large constant noises or time-varying noises. In contrast, the proposed
approach works well and has a low tracking error comparable to noise-free
situations.
PMID- 28422690
TI - Doubly Nonparametric Sparse Nonnegative Matrix Factorization Based on Dependent
Indian Buffet Processes.
AB - Sparse nonnegative matrix factorization (SNMF) aims to factorize a data matrix
into two optimized nonnegative sparse factor matrices, which could benefit many
tasks, such as document-word co-clustering. However, the traditional SNMF
typically assumes the number of latent factors (i.e., dimensionality of the
factor matrices) to be fixed. This assumption makes it inflexible in practice. In
this paper, we propose a doubly sparse nonparametric NMF framework to mitigate
this issue by using dependent Indian buffet processes (dIBP). We apply a
correlation function for the generation of two stick weights associated with each
column pair of factor matrices while still maintaining their respective marginal
distribution specified by IBP. As a consequence, the generation of two factor
matrices will be columnwise correlated. Under this framework, two classes of
correlation function are proposed: 1) using bivariate Beta distribution and 2)
using Copula function. Compared with the single IBP-based NMF, this paper jointly
makes two factor matrices nonparametric and sparse, which could be applied to
broader scenarios, such as co-clustering. This paper is seen to be much more
flexible than Gaussian process-based and hierarchial Beta process-based dIBPs in
terms of allowing the two corresponding binary matrix columns to have greater
variations in their nonzero entries. Our experiments on synthetic data show the
merits of this paper compared with the state-of-the-art models in respect of
factorization efficiency, sparsity, and flexibility. Experiments on real-world
data sets demonstrate the efficiency of this paper in document-word co-clustering
tasks.
PMID- 28422691
TI - Event-Sampled Direct Adaptive NN Output- and State-Feedback Control of Uncertain
Strict-Feedback System.
AB - In this paper, a novel event-triggered implementation of a tracking controller
for an uncertain strict-feedback system is presented. Neural networks (NNs) are
utilized in the backstepping approach to design a control input by approximating
unknown dynamics of the strict-feedback nonlinear system with event-sampled
inputs. The system state vector is assumed to be unknown and an NN observer is
used to estimate the state vector. By using the estimated state vector and
backstepping design approach, an event-sampled controller is introduced. As part
of the controller design, first, input-to-state-like stability for a continuously
sampled controller that has been injected with bounded measurement errors is
demonstrated, and subsequently, an event-execution control law is derived, such
that the measurement errors are guaranteed to remain bounded. Lyapunov theory is
used to demonstrate that the tracking errors, the observer estimation errors, and
the NN weight estimation errors for each NN are locally uniformly ultimately
bounded in the presence bounded disturbances, NN reconstruction errors, as well
as errors introduced by event sampling. Simulation results are provided to
illustrate the effectiveness of the proposed controllers.
PMID- 28422692
TI - Safe Screening Rules for Accelerating Twin Support Vector Machine Classification.
AB - The twin support vector machine (TSVM) is widely used in classification problems,
but it is not efficient enough for large-scale data sets. Furthermore, to get the
optimal parameter, the exhaustive grid search method is applied to TSVM. It is
very time-consuming, especially for multiparameter models. Although many
techniques have been presented to solve these problems, all of them always affect
the performance of TSVM to some extent. In this paper, we propose a safe
screening rule (SSR) for linear-TSVM, and give a modified SSR (MSSR) for
nonlinear TSVM, which contains multiple parameters. The SSR and MSSR can delete
most training samples and reduce the scale of TSVM before solving it. Sequential
versions of SSR and MSSR are further introduced to substantially accelerate the
whole parameter tuning process. One important advantage of SSR and MSSR is that
they are safe, i.e., we can obtain the same solution as the original problem by
utilizing them. Experiments on eight real-world data sets and an imbalanced data
set with different imbalanced ratios demonstrate the efficiency and safety of SSR
and MSSR.
PMID- 28422693
TI - Singularities of Three-Layered Complex-Valued Neural Networks With Split
Activation Function.
AB - There are three important concepts related to learning processes in neural
networks: reducibility, nonminimality, and singularity. Although the definitions
of these three concepts differ, they are equivalent in real-valued neural
networks. This is also true of complex-valued neural networks (CVNNs) with hidden
neurons not employing biases. The situation of CVNNs with hidden neurons
employing biases, however, is very complicated. Exceptional reducibility was
found, and it was shown that reducibility and nonminimality are not the same.
Irreducibility consists of minimality and exceptional reducibility. The
relationship between minimality and singularity has not yet been established. In
this paper, we describe our surprising finding that minimality and singularity
are independent. We also provide several examples based on exceptional
reducibility.
PMID- 28422694
TI - Synchronization Criteria for Discontinuous Neural Networks With Mixed Delays via
Functional Differential Inclusions.
AB - This paper investigates the issue of global exponential synchronization for a
class of general neural networks that contains discontinuous activation functions
and mixed time delays. Functional differential inclusions and nonsmooth analysis
theories are used as bases to design discontinuous controllers, such that the
discontinuous neural networks can be exponential complete synchronized. This
novel approach and its applicability to neural networks with continuous
activations are also easily verified. Several numerical examples demonstrate the
practicality and effectiveness of the design method.
PMID- 28422695
TI - On the Impact of Regularization Variation on Localized Multiple Kernel Learning.
AB - This brief analyzes the effects of regularization variations in the localized
kernel weights on the hypothesis generated by localized multiple kernel learning
(LMKL) algorithms. Recent research on LMKL includes imposing different
regularizations on the localized kernel weights and has led to varying
formulations and solution strategies. Following the stability analysis theory as
presented by Bousquet and Elisseeff, we give stability bounds based on the norm
of the variation of localized kernel weights for three LMKL methods cast in the
support vector machine classification framework, including vector -norm LMKL,
matrix-regularized -norm LMKL, and samplewise -norm LMKL. Further comparison of
these bounds helps to qualitatively reveal the performance differences produced
by these regularization methods, that is, matrix-regularized LMKL achieves
superior performance, followed by vector -norm LMKL and samplewise -norm LMKL.
Finally, a set of experimental results on ten benchmark machine learning UCI data
sets is reported and shown to empirically support our theoretical analysis.
PMID- 28422696
TI - New Conditions for Global Asymptotic Stability of Memristor Neural Networks.
AB - Recent papers in the literature introduced a class of neural networks (NNs) with
memristors, named dynamic-memristor (DM) NNs, such that the analog processing
takes place in the charge-flux domain, instead of the typical current-voltage
domain as it happens for Hopfield NNs and standard cellular NNs. One key
advantage is that, when a steady state is reached, all currents, voltages, and
power of a DM-NN drop off, whereas the memristors act as nonvolatile memories
that store the processing result. Previous work in the literature addressed
multistability of DM-NNs, i.e., convergence of solutions in the presence of
multiple asymptotically stable equilibrium points (EPs). The goal of this paper
is to study a basically different dynamical property of DM-NNs, namely, to
thoroughly investigate the fundamental issue of global asymptotic stability (GAS)
of the unique EP of a DM-NN in the general case of nonsymmetric neuron
interconnections. A basic result on GAS of DM-NNs is established using Lyapunov
method and the concept of Lyapunov diagonally stable matrices. On this basis,
some relevant classes of nonsymmetric DM-NNs enjoying the property of GAS are
highlighted.
PMID- 28422697
TI - Manifold Regularized Correlation Object Tracking.
AB - In this paper, we propose a manifold regularized correlation tracking method with
augmented samples. To make better use of the unlabeled data and the manifold
structure of the sample space, a manifold regularization-based correlation filter
is introduced, which aims to assign similar labels to neighbor samples.
Meanwhile, the regression model is learned by exploiting the block-circulant
structure of matrices resulting from the augmented translated samples over
multiple base samples cropped from both target and nontarget regions. Thus, the
final classifier in our method is trained with positive, negative, and unlabeled
base samples, which is a semisupervised learning framework. A block optimization
strategy is further introduced to learn a manifold regularization-based
correlation filter for efficient online tracking. Experiments on two public
tracking data sets demonstrate the superior performance of our tracker compared
with the state-of-the-art tracking approaches.
PMID- 28422698
TI - Dissipativity-Based Resilient Filtering of Periodic Markovian Jump Neural
Networks With Quantized Measurements.
AB - The problem of dissipativity-based resilient filtering for discrete-time periodic
Markov jump neural networks in the presence of quantized measurements is
investigated in this paper. Due to the limited capacities of network medium, a
logarithmic quantizer is applied to the underlying systems. Considering the fact
that the filter is realized through a network, randomly occurring parameter
uncertainties of the filter are modeled by two mode-dependent Bernoulli
processes. By establishing the mode-dependent periodic Lyapunov function,
sufficient conditions are given to ensure the stability and dissipativity of the
filtering error system. The filter parameters are derived via solving a set of
linear matrix inequalities. The merits and validity of the proposed design
techniques are verified by a simulation example.
PMID- 28422699
TI - Hemorrhage Prediction Models in Surgical Intensive Care: Bedside Monitoring Data
Adds Information to Lab Values.
AB - Hemorrhage is a frequent complication in surgery patients; its identification and
management have received increasing attention as a target for quality improvement
in patient care in the Intensive Care Unit (ICU). The purposes of this work were
1) to find an early detection model for hemorrhage by exploring the range of data
mining methods that are currently available, and 2) to compare prediction models
utilizing continuously measured physiological data from bedside monitors to those
using commonly obtained laboratory tests. We studied 3766 patients admitted to
the University of Virginia Health System Surgical Trauma Burn ICU. Hemorrhage was
defined as three or more units of red blood cells transfused within 24 h without
red blood cell transfusion in the preceding 24 h. 222 patients (5.9%) experienced
a hemorrhage, and multivariate models based on vital signs and their trends
showed good results (AUC = 76.1%). The hematocrit, not surprisingly, had
excellent performance (AUC = 87.7%). Models that included both continuous
monitoring and laboratory tests had the best performance (AUC = 92.2%). The
results point to a combined strategy of continuous monitoring and intermittent
lab tests as a reasonable clinical approach to the early detection of hemorrhage
in the surgical ICU.
PMID- 28422700
TI - Adaptive Fuzzy Control for Nonstrict Feedback Systems With Unmodeled Dynamics and
Fuzzy Dead Zone via Output Feedback.
AB - This paper investigates the problem of observer-based adaptive fuzzy control for
a category of nonstrict feedback systems subject to both unmodeled dynamics and
fuzzy dead zone. Through constructing a fuzzy state observer and introducing a
center of gravity method, unmeasurable states are estimated and the fuzzy dead
zone is defuzzified, respectively. By employing fuzzy logic systems to identify
the unknown functions. And combining small-gain approach with adaptive
backstepping control technique, a novel adaptive fuzzy output feedback control
strategy is developed, which ensures that all signals involved are semi-globally
uniformly bounded. Simulation results are given to demonstrate the effectiveness
of the presented method.
PMID- 28422701
TI - Aperiodic Optimal Linear Estimation for Networked Systems With Communication
Uncertainties.
AB - The aperiodic optimal linear estimator design problem is investigated in this
paper for networked systems with communication uncertainties, including delays
and data losses, where the sampling and estimation are nonuniform and
asynchronous. Based on the idea of measurement fusion, two approaches are
proposed to design the aperiodic estimators, and it is shown that the estimator
is equivalent to that designed by the measurement augmentation method in
performance. Moreover, the estimation performance is improved by using a newly
proposed measurement retransmission scheme as compared with the commonly used
hold-input and zero-input schemes, by which the lost measurements are never used
once they are lost.
PMID- 28422702
TI - Neuronal State Estimation for Neural Networks With Two Additive Time-Varying
Delay Components.
AB - This paper is concerned with the state estimation for neural networks with two
additive time-varying delay components. Three cases of these two time-varying
delays are fully considered: 1) both delays are differentiable uniformly bounded
with delay-derivative bounded by some constants; 2) one delay is continuous
uniformly bounded while the other is differentiable uniformly bounded with delay
derivative bounded by certain constants; and 3) both delays are continuous
uniformly bounded. First, an extended reciprocally convex inequality is
introduced to bound reciprocally convex combinations appearing in the derivative
of some Lyapunov-Krasovskii functional. Second, sufficient conditions are derived
based on the extended inequality for three cases of time-varying delays,
respectively. Third, a linear-matrix-inequality-based approach with two tuning
parameters is proposed to design desired Luenberger estimators such that the
error system is globally asymptotically stable. This approach is then applied to
state estimation on neural networks with a single interval time-varying delay.
Finally, two numerical examples are given to illustrate the effectiveness of the
proposed method.
PMID- 28422703
TI - Differential hemoglobin A sequestration between hemodialysis modalities.
AB - This report evaluates plasma protein patterns, dialysates and protein analysis of
used dialysis membranes from the same patient under hemodialysis in three
separate modalities, using high-flux membranes in concentration-driven transport
(HD), convection-driven hemofiltration (HF) and combined hemodialfiltration
(HDF). The plasma protein changes induced by each of the three dialysis
modalities showed small differences in proteins identified towards our previous
plasma analyses of chronic kidney disease (CKD) patients. The used dialysate
peptide concentrations likewise exhibited small differences among the modalities
and varied in the same relative order as the plasma changes, with protein losses
in the order HD>HDF>HF. The membrane protein deposits allowed quantification of
the relative Hb removal ratios as ~1.7 for HD and ~1.2 for HDF vs. ~1.0 for HF.
Hence, plasma protein alterations, dialysate peptide contents and membrane Hb
deposits all identify HD as the modality with the most extensive filtration
results and exemplifies the accessibility of protein analysis of used membrane
filters for evaluation of dialysis efficiencies.
PMID- 28422704
TI - Influencing factors on high-risk sexual behaviors in young people: an ecological
perspective.
AB - Background In recent years, high-risk sexual behaviors due to their negative
consequences both for the individual and society have received more attention
than other high-risk behaviors. Objective The aim of this study was to review the
influencing factors of high-risk sexual behaviors among young people from an
ecological point of view. Methods This review was conducted through searching
databases including PubMed, Web of Science, Scopus, Google Scholar and the
Cochrane Library with keywords such as sexual risk-taking behavior, high-risk
sex, unprotected sex and unsafe sex. The relevant papers published between 1995
and 2016 were extracted. After reviewing the abstract and full text of the
articles, 45 papers were used to write this article. Results From an ecological
theory approach, factors which influence high-risk sexual behaviors are divided
into three categories - the microsystem, the mesosystem and the macrosystem. The
microsystem includes factors such as age, gender, race, marital status, place of
residence, religion, level of education, personality traits, psychological
problems, childhood experiences, body image and coincidence of high-risk
behaviors; the mesosystem includes factors such as family structure, peers and
sex education; in the macrosystem, the impact of culture and traditions of the
society, economic status and the media are presented. Conclusion Given that high
risk sexual behaviors often have multiple causes, it seems that health
policymakers must consider multi-dimensional interventions to influence high-risk
sexual behaviors based on the ecological approach.
PMID- 28422705
TI - Plasma kisspeptin and ghrelin levels in puberty variant cases.
AB - BACKGROUND: The aim of this study was to determine the serum levels of kisspeptin
and ghrelin (GAH), as well as the relationship of these two peptides with each
other in premature thelarche (PT) and premature adrenarche (PA) cases and to
investigate the possibility of using these peptides as markers in the
differentiation of puberty disorders. METHODS: A PT group aged 1-8 years (n =
40), a PA group aged 1-9 years (n = 23, female/male = 20/3) and control groups
consistent with each of the previous groups in terms of age and gender were
created for the study. Kisspeptin and ghrelin levels were measured with ELISA
methods from blood samples drawn while fasting in the morning. RESULTS: When the
PT group was compared with the controls, the plasma kisspeptin levels of the
cases were significantly higher than the control group (165.47 +/- 15.45 pmol/L,
96.82 +/- 12.33 pmol/L, p = 0.005, respectively). Kisspeptin levels in the PA
group did not show a difference with the control group (121.36 +/- 17.99 pmol/L,
95.52 +/- 11.54 pmol/L, p = 0.249, respectively). No significant difference could
be found when GAH levels in the PT and PA groups were compared with controls. No
significant correlation was found between kisspeptin and GAH levels in the PT and
PA groups. CONCLUSIONS: Our results indicate that kisspeptin plays an important
role in the PT, but GAH is not associated with puberty disorders.
PMID- 28422706
TI - Adult hippocampal neurogenesis: an important target associated with
antidepressant effects of exercise.
AB - Depression is a prevalent devastating mental disorder that affects the normal
life of patients and brings a heavy burden to whole society. Although many
efforts have been made to attenuate depressive/anxiety symptoms, the current
clinic antidepressants have limited effects. Scientists have long been making
attempts to find some new strategies that can be applied as the alternative
antidepressant therapy. Exercise, a widely recognized healthy lifestyle, has been
suggested as a therapy that can relieve psychiatric stress. However, how exercise
improves the brain functions and reaches the antidepressant target needs
systematic summarization due to the complexity and heterogeneous feature of
depression. Brain plasticity, especially adult neurogenesis in the hippocampus,
is an important neurophysiology to facilitate animals for neurogenesis can occur
in not only humans. Many studies indicated that an appropriate level of exercise
can promote neurogenesis in the adult brains. In this article, we provide
information about the antidepressant effects of exercise and its implications in
adult neurogenesis. From the neurogenesis perspective, we summarize evidence
about the effects of exercise in enhancing neurogenesis in the hippocampus
through regulating growth factors, neurotrophins, neurotransmitters and
metabolism as well as inflammations. Taken together, a large number of published
works indicate the multiple benefits of exercise in the brain functions of
animals, particularly brain plasticity like neurogenesis and synaptogenesis.
Therefore, a new treatment method for depression therapy can be developed by
regulating the exercise activity.
PMID- 28422707
TI - Factors underlying cognitive decline in old age and Alzheimer's disease: the role
of the hippocampus.
AB - There are many factors that strongly influence the aetiology, development, and
progression of cognitive decline in old age, mild cognitive impairment (MCI), and
Alzheimer's disease (AD). These factors include not only different personality
traits and moods but also lifestyle patterns (e.g. exercise and diet) and
awareness levels that lead to cognitive decline in old age. In this review, we
discuss how personality traits, mood states, and lifestyle impact brain and
behaviour in older adults. Specifically, our review shows that these lifestyle
and personality factors affect several brain regions, including the hippocampus,
a region key for memory that is affected by cognitive decline in old age as well
as AD. Accordingly, appropriate recommendations are presented in this review to
assist individuals in decreasing chances of MCI, dementia, AD, and associated
symptoms.
PMID- 28422708
TI - A brief essay on non-pharmacological treatment of Alzheimer's disease.
AB - Current pharmacological therapies for Alzheimer's disease (AD) do not modify its
course and are not always beneficial. Therefore, the optimization of quality of
life represents the best possible outcome achievable in all stages of the
disease. Cognitive and behavioural rehabilitation represents the main therapeutic
approach for this purpose, also in order to mitigate indirectly the burden of
distress of family caregivers. The aim of this mini-review is to go through this
theme by discussing cognitive activation, virtual reality and neuromodulation
techniques. The practices summarized in this essay are not alternative but,
often, complementary therapies to standardized pharmacological treatment. The
present mini-review has found encouraging results but also the need for more
conclusive evidence for all types of non-invasive/non-pharmacological treatment
of AD.
PMID- 28422709
TI - Preterm birth among women living within 600 meters of high voltage overhead Power
Lines: a case-control study.
AB - AIM: The issue of preterm birth due to exposure to magnetic fields from power
lines is unclear. Exposure to electromagnetic field in uterus has been
hypothesized as possible preterm birth. The aim of the present study was to
determine whether living closer to high voltage power lines increased the risk of
preterm labor. METHODS: In a nested case-control study, 135 cases of singleton
live spontaneous preterm birth in Rohani hospital, Babol, Iran, during the period
between 2013 and 2014 were studied. The 150 control subjects were singleton term
live birth in the same year of birth and city of residence using randomized-digit
dialing. The shortest distance to any of the high voltage power lines to the
maternal residence during pregnancy was measured using ArcGIS software for every
case and control. To test the association between the preterm births and the
residential proximity to power lines, stepwise multiple logistic regression was
used. RESULTS: There were 28 households, 20 cases (14.8%) and 8 controls (5.3%)
situated within 600 meters of high voltage power lines. The adjusted OR for
spontaneous preterm birth and birth defect in women who were living in less than
600 meters from high voltage power lines was higher compared to those living at
farther distance (OR = 3.28, CI: 1.37 to 7.85) and (OR = 5.05, CI: 1.52 to
16.78), respectively. CONCLUSIONS: Therefore, installing overhead power lines and
stations within 600 meters or making overhead underground would be useful in the
prevention of both preterm birth and birth defect.
PMID- 28422710
TI - The role of metabolic tumor volume (MTV) measured by [18F] FDG PET/CT in
predicting EGFR gene mutation status in non-small cell lung cancer.
AB - Many noninvasive methods have been explored to determine the mutation status of
the epidermal growth factor receptor (EGFR) gene, which is important for
individualized treatment of non-small cell lung cancer (NSCLC). We evaluated
whether metabolic tumor volume (MTV), a parameter measured by [18F]
fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT)
might help predict EGFR mutation status in NSCLC. Overall, 87 patients who
underwent EGFR genotyping and pretreatment PET/CT between January 2013 and
September 2016 were reviewed. Clinicopathologic characteristics and metabolic
parameters including MTV were evaluated. Univariate and multivariate analyses
were used to assess the independent variables that predict mutation status to
create prediction models. Forty-one patients (41/87) were identified as having
EGFR mutations. The multivariate analysis showed that patients with lower MTV
(MTV<=11.0 cm3, p=0.001) who were non-smokers (p=0.037) and had a peripheral
tumor location (p=0.033) were more likely to have EGFR mutations. Prediction
models using these criteria for EGFR mutation yielded a high AUC (0.805, 95% CI
0.712-0.899), which suggests that the analysis had good discrimination. In
conclusion, NSCLC patients with EGFR mutations showed significantly lower MTV
than patients with wild-type EGFR. Prediction models based on MTV and
clinicopathologic characteristics could provide more information for the
identification of EGFR mutations.
PMID- 28422711
TI - Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived
tumor xenograft models.
AB - Aberrant activation of histone lysine-specific demethylase (LSD1) increases
tumorigenicity; hence, LSD1 is considered a therapeutic target for various human
cancers. Although melatonin, an endogenously produced molecule, may defend
against various cancers, the precise mechanism involved in its anti-oral cancer
effect remains unclear. Patient-derived tumor xenograft (PDTX) models are
preclinical models that can more accurately reflect human tumor biology compared
with cell line xenograft models. Here, we evaluated the anticancer activity of
melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral
squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we
examined whether aberrant LSD1 overexpression in OSCC is associated with poor
prognosis. We also evaluated the action mechanism of melatonin against OSCC with
lymphatic metastases by using the PDTX models. Our results indicated that
melatonin, at pharmacological concentrations, significantly suppresses cell
proliferation in a dose- and time-dependent manner. The observed suppression of
proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in
oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that
the beneficial effects of melatonin in reducing oral cancer cell proliferation
are associated with reduced LSD1 expression in vivo and in vitro.
PMID- 28422712
TI - Combination analysis of NOS3, ABCB1 and IL23R polymorphisms with alcohol-induced
osteonecrosis of the femoral head risk in Chinese males.
AB - BACKGROUND: Common variants of multiple genes played a crucial role in
osteonecrosis of the femoral head (ONFH) onset which was proved by many previous
reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related
to individual differences in alcohol sensitivity and the development of alcohol
induced ONFH. METHODS: In this case-control study, we evaluated 8 SNPs in three
genes in the Chinese Han population including 355 male cases and 355 healthy male
controls. These SNPs were genotyped by Sequenom MassARRAY RS1000. To identify
their relationship with alcohol-induced ONFH susceptibility using chi2 test and
genetic model analysis. RESULTS: We found an association with alcohol-induced
ONFH susceptibility for 4 SNPs (rs743506, rs3918184, rs13233308 and rs6693831) in
three genes after adjusted by age. The genotype "G/A" of rs743506 in NOS3 gene
acts as a risk factor in genotype (P = 0.003), dominant (P = 0.048), recessive (P
= 0.005) and additive model(P = 0.006); The genotype "T/C" of rs3918184 in NOS3
gene acts as a risk factor in genotype (P = 0.012) and recessive model (P =
0.009); The genotype "T/C" of rs13233308 in ABCB1 gene acts as a risk factor in
genotype (P = 0.038) and additive model(P = 0.041); The genotype "T/C" of
rs6693831 in IL23R gene acts as a protective factor in genotype model (P =
0.046). CONCLUSIONS: This study provides evidence for three alcohol-induced ONFH
susceptibility genes (NOS3, ABCB1 and IL23R) in Chinese males and polymorphisms
of them may be associated with alcohol-induced ONFH risk.
PMID- 28422713
TI - SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of
serine phosphorylation of STAT1 and STAT5 transactivation domains.
AB - Inhibition of oncogenic transcriptional programs is a promising therapeutic
strategy. A substituted tricyclic benzimidazole, SEL120-34A, is a novel inhibitor
of Cyclin-dependent kinase 8 (CDK8), which regulates transcription by associating
with the Mediator complex. X-ray crystallography has shown SEL120-34A to be a
type I inhibitor forming halogen bonds with the protein's hinge region and
hydrophobic complementarities within its front pocket. SEL120-34A inhibits
phosphorylation of STAT1 S727 and STAT5 S726 in cancer cells in vitro.
Consistently, regulation of STATs- and NUP98-HOXA9- dependent transcription has
been observed as a dominant mechanism of action in vivo. Treatment with the
compound resulted in a differential efficacy on AML cells with elevated STAT5
S726 levels and stem cell characteristics. In contrast, resistant cells were
negative for activated STAT5 and revealed lineage commitment. In vivo efficacy in
xenotransplanted AML models correlated with significant repression of STAT5 S726.
Favorable pharmacokinetics, confirmed safety and in vivo efficacy provide a
rationale for the further clinical development of SEL120-34A as a personalized
therapeutic approach in AML.
PMID- 28422714
TI - Toll like receptor 3 as an immunotherapeutic target for KRAS mutated colorectal
cancer.
AB - New therapeutic interventions are essential for improved management of patients
with metastatic colorectal cancer (mCRC). This is especially critical for those
patients whose tumors harbor a mutation in the KRAS oncogene (40-45% of all
patients). This patient cohort is excluded from receiving anti-EGFR monoclonal
antibodies that have added a significant therapeutic benefit for KRAS wild type
CRC patients. Reovirus, a double stranded (ds) RNA virus is in clinical
development for patients with chemotherapy refractory KRAS mutated tumors. Toll
Like Receptor (TLR) 3, a member of the toll like receptor family of the host
innate immune system is the pattern recognition motif for dsRNA pathogens. Using
TLR3 expressing commercial HEK-BlueTM-hTLR3 cells we confirm that TLR3 is the
host pattern recognition motif responsible for the detection of reovirus.
Further, our investigation with KRAS mutated HCT116 cell line showed that
effective expression of host TLR3 dampens the infection potential of reovirus by
mounting a robust innate immune response. Down regulation of TLR3 expression with
siRNA improves the anticancer activity of reovirus. In vivo experiments using
human CRC cells derived xenografts in athymic mice further demonstrate the
beneficial effects of TLR3 knock down by improving tumor response rates to
reovirus. Strategies to mitigate the TLR3 response pathway can be utilized as a
tool towards improved reovirus efficacy to specifically target the dissemination
of KRAS mutated CRC.
PMID- 28422715
TI - A novel BMX variant promotes tumor cell growth and migration in lung
adenocarcinoma.
AB - The non-receptor tyrosine kinase BMX has been reported in several solid tumors.
However, the alternative splicing of BMX and its clinical relevance in lung
cancer remain to be elucidated. Exon1.0 array was used to identify a novel
alternative splicing of BMX, BMXDeltaN, which was confirmed by rapid
amplification of cDNA ends and reverse transcription-polymerase chain reaction.
BMXDeltaN, resulting from exon skipping with excluding exon 1 to exon 8 of BMX
gene, was found in 12% human lung adenocarcinoma specimens. BMXDeltaN is not
found in paired pathologically normal lungs and positively correlated with EGFR
mutation in lung adenocarcinomas. Moreover, BMXDeltaN increases cell
proliferation, neoplastic transformation, and migratory property of human non
small cell lung cancer cells. The function of BMXDeltaN in lung cancer might be
presumably due to enhanced ERK signaling.
PMID- 28422716
TI - Sequential evaluation of CALR mutant burden in patients with myeloproliferative
neoplasms.
AB - We investigated the variation of CALR-mutant burden during follow-up in 105 CALR
mutant MPN and compared it to the variation of JAK2-mutant burden in 226 JAK2
mutant MPN.The median allele burden at last evaluation was significantly higher
than at first evaluation in essential thrombocythemia (ET) (49.5% vs 45%, P <
.001) but not in primary myelofibrosis (PMF) (52% vs 51%, P 0.398). Median values
of slope were positive both in ET (0.071) and in PMF (0.032). In CALR-mutant ET
there was a difference between natural and therapy-related slope (P 0.006).In the
JAK2-mutated cohort, the median allele burden at last evaluation was not
different respect to that at first evaluation, neither in ET (22.9% vs 23.2%, P =
0.216) nor in PMF (50.5% vs 45.0%, P = 0.809), despite a positive slope.
Multivariate analysis to evaluate the effect of mutation (CALR vs JAK2) on the
slope of mutant burden in not treated pts with a positive slope adjusting for
diagnosis (ET vs PMF) showed a trend toward a higher increase of mutant burden in
CALR vs JAK2 (beta = 0.19, P = 0.061) with no difference between diagnosis (P =
0.419). The findings of this study suggest that clonal expansion in CALR-mutant
MPN is faster than that observed in JAK2-mutant MPN.
PMID- 28422717
TI - C3orf21 ablation promotes the proliferation of lung adenocarcinoma, and its
mutation at the rs2131877 locus may serve as a susceptibility marker.
AB - In this study, we investigated the role of C3orf21 gene polymorphism at the
rs2131877 locus and its contribution to lung adenocarcinoma pathogenesis. Normal
lung and tumor tissue sections were collected from fifteen patients with lung
adenocarcinoma for chromosome 3 open reading frame 21 (C3orf21) genotype
analysis. In addition, a retrospective analysis was performed to assess the
association between C3orf21 genotype and tumor markers from patient samples used
in our previously published study. In parallel, we also manipulated C3orf21 gene
expression either by overexpressing or ablating it in a MSTO-211H human lung
cancer cell line to further understand its contribution to cell proliferation,
apoptosis and migration. Our results indicated that the patients with smoking
history had a significantly increased mutation (rs2131877 T/C+C/C genotype) rate
(p = 0.025), in addition to higher values for the CYF211 and NSE tumor markers (p
= 0.014 and p = 0.031, respectively). The retrospective analysis also confirmed
that the NSE marker value was higher in patients with a C3orf21 rs2131877 T/C+C/C
genotype. Furthermore, our in vitro data indicated that C3orf21 ablation promoted
lung cancer cell proliferation, inhibited apoptosis and accelerated cell
migration. Overall, our study concluded that C30rf21 rs 2131877 T/C+C/C genotype
patients may experience increased nicotine addiction and that C30rf21 can likely
serve as a susceptibility marker for lung adenocarcinoma with a higher degree of
malignancy.
PMID- 28422718
TI - Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine
workflow for BRCA1 and BRCA2 genetic testing.
AB - In this study, we validated the analytical performance of BRCA1/2 sequencing
using Ion Torrent's new bench-top sequencer with amplicon panel with optimized
bioinformatics pipelines. Using 43 samples that were previously validated by
Illumina's MiSeq platform and/or by Sanger sequencing/multiplex ligation
dependent probe amplification, we amplified the target with the OncomineTM BRCA
Research Assay and sequenced on Ion Torrent S5 XL (Thermo Fisher Scientific,
Waltham, MA, USA). We compared two bioinformatics pipelines for optimal
processing of S5 XL sequence data: the Torrent Suite with a plug-in Torrent
Variant Caller (Thermo Fisher Scientific), and commercial NextGENe software
(Softgenetics, State College, PA, USA). All expected 681 single nucleotide
variants, 15 small indels, and three copy number variants were correctly called,
except one common variant adjacent to a rare variant on the primer-binding site.
The sensitivity, specificity, false positive rate, and accuracy for detection of
single nucleotide variant and small indels of S5 XL sequencing were 99.85%, 100%,
0%, and 99.99% for the Torrent Variant Caller and 99.85%, 99.99%, 0.14%, and
99.99% for NextGENe, respectively. The reproducibility of variant calling was
100%, and the precision of variant frequency also showed good performance with
coefficients of variation between 0.32 and 5.29%. We obtained highly accurate
data through uniform and sufficient coverage depth over all target regions and
through optimization of the bioinformatics pipeline. We confirmed that our
platform is accurate and practical for diagnostic BRCA1/2 testing in a clinical
laboratory.
PMID- 28422719
TI - Fbxw7 haploinsufficiency loses its protection against DNA damage and accelerates
MNU-induced gastric carcinogenesis.
AB - Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein
substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor
suppressor via inducing apoptosis and growth arrest in various kinds of tumors.
To clarify the initiating role in gastric carcinogenesis as well as the
histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we
generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with
chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age. We also
treated mouse embryo fibroblasts (MEFs) from Fbxw7+/- and Fbxw7+/+ mice with MNU
and examined cell DNA damage via comet assay. The protein expression of Fbxw7 and
its substrate c-Myc from mouse tumors, as well as human tumors sampled from six
patients, were detected by Western blot. As results, the tumor incidence was
obviously higher in Fbxw7+/- mice (13/20) than in Fbxw7+/+ mice (6/20) after 35
week observation. Intestinal metaplasia (P = 0.013) and dysplasia (P = 0.036)
were more severe in Fbxw7+/- mice than in Fbxw7+/+ mice. The repair potential of
DNA damage was suppressed in MEFs from Fbxw7+/- mice after MNU exposure.
Increased c-Myc expression was accompanied by decreased Fbxw7 protein expression
in tumor tissues from mouse and patients. In conclusion, Fbxw7 haploinsufficiency
increased the risk of gastric carcinogenesis induced by MNU, which is associated
with the accumulation of DNA damage as well as c-Myc oncoprotein.
PMID- 28422720
TI - Overexpression of NOX4 predicts poor prognosis and promotes tumor progression in
human colorectal cancer.
AB - NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS)
production, has been increasingly reported to be involved in tumorigenesis and/or
tumor progression, but limited data are available regarding the role of NOX4 in
colorectal carcinoma (CRC). We retrieved six independent investigations from
Oncomine database and found that NOX4 is highly expressed in CRC tissues compared
with corresponding normal controls. Similar results were also found in clinical
specimens at both mRNA and protein levels. Immunohistochemical analysis indicated
that NOX4 overexpression was highly correlated with T classification, N
classification, distant metastasis, and poor prognosis of CRC patients, which was
also confirmed by GSE14333 and GSE17536 datasets from the Gene Expression
Omnibus. Furthermore, we demonstrated that when NOX4 expression was knocked down
by siRNAs, cell proliferation, cell-cycle and apoptosis, migration and invasion
were significantly altered in CRC cell lines HCT116 and LOVO. Meanwhile, NOX4
promoted cancer cell proliferation and apoptosis, migration and invasion by
regulating the expression of relevant genes. By these approaches we aim to
elucidate NOX4 may be a reliable prognostic factor or therapeutic target in CRC.
PMID- 28422721
TI - Functional analysis implicating the SNP rs61552325 in ERBB2 as an effector for
androgen-insensitive prostate cancer cell invasion.
AB - BACKGROUND: As one of the most common cancers in men, the pathogenesis of
prostate cancer has been widely researched. Aberrant activation of the erb-b2
receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in
metastatic prostate cancer. In our previous study, we demonstrated that
rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate
cancer. Therefore, we initially studied the effect of rs61552325 on androgen
independent prostate cancer cell metastasis. RESULTS: Bioinformatic results
demonstrated that the mutant Pro1140Ala likely decrease the stability of the
ERBB2 protein and its interactions. The mean migration rate after 6 h for PC3
minor variant cells which carried the G allele was 1.28-fold higher than major
variant PC3 cells that carried the C allele (P = 0.016). The mean invasion rate
of DU145 putative minor variant cells was 0.40 reducer than negative control
cells (P = 5.9E-04). METHODS: rs61552325 major variant (C allele) and minor
variant (G allele) were produced by site directed mutagenesis and transfected
into DU145 and PC3 cells. A wound healing assay was performed to compare
migration abilities between alleles. After knocking down endogenous ERBB2 and
then expressing the rs61552325 minor variant, invasion abilities were evaluated
with a transwell assay using DU145 and PC3 cells. CONCLUSIONS: Our data showed
that the rs61552325 major variant decreases PC3 cell migration and its minor
variant depresses DU145 cell invasion, suggesting that rs61552325 is likely an
important change during prostate cancer invasion.
PMID- 28422722
TI - The clinical value, regulatory mechanisms, and gene network of the cancer-testis
gene STK31 in pancreatic cancer.
AB - We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its
potential clinical value, regulatory mechanisms, and gene network in pancreatic
cancer (PC). Gene expression data were generated from normal organ samples and
pancreatic cancer samples from three public databases. STK31 expression patterns
in normal and PC tissues were identified, and we explored its regulatory
mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were
performed and an STK31 protein-protein interaction (PPI) network was constructed.
STK31 was confirmed as a CT gene in PC and its expression was significantly
higher in patients with new neoplasm compared with patients without new neoplasm
(P = 0.046) and in more advanced pathologic stages than in earlier stages (P =
0.002); methylation level correlated negatively with STK31 expression. In total,
757 STK31-related genes were identified, and were significantly enriched in terms
of polymorphisms and alternative splicings. The PPI network predicted that STK31
was physically associated with the PIWI (originally P-element Induced WImpy
testis in Drosophila) and Tudor families.
PMID- 28422723
TI - Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is
associated with improved patient survival.
AB - Colorectal mucinous adenocarcinoma (MAC) and serrated adenocarcinoma (SAC) share
many characteristics, including right-side colon location, frequent mucin
production, and various molecular features. This study examined the frequency of
SAC morphology in MACs. We assessed the correlation of SAC morphology with
clinicopathological parameters, molecular characteristics, and patient prognosis.
Eighty-eight colorectal MACs were collected and reviewed for SAC morphology
according to Makinen's criteria. We sequenced KRAS and BRAF, assessed CpG island
methylator phenotype (CIMP) frequency, and analyzed DNA mismatch repair enzyme
levels using immunohistochemistry in tumor samples. SAC morphology was observed
in 38% of MACs, and was associated with proximal location (P=0.001), BRAF
mutation (P=0.042), CIMP-positive status (P=0.023), and contiguous traditional
serrated adenoma (P=0.019). Multivariate analysis revealed that MACs without both
SAC morphology and CIMP-positive status exhibited 3.955 times greater risk of
cancer relapse than MACs having both characteristics or either one (P=0.035). Our
results show that two MAC groups with distinct features can be identified using
Makinen's criteria, and suggest a favorable prognostic role for the serrated
neoplastic pathway in colorectal MAC.
PMID- 28422724
TI - Utilizing combinatorial engineering to develop Tie2 targeting antagonistic
angiopoetin-2 ligands as candidates for anti-angiogenesis therapy.
AB - In many human cancers, the receptor tyrosine kinase (RTK) Tie2 plays important
roles in mediating proliferation, survival, migration and angiogenesis. Thus,
molecules that could potently inhibit activation of the Tie2 receptor would have
a significant impact on cancer therapy. Nevertheless, attempts to develop Tie2
targeted inhibitors have met with little success, and there is currently no FDA
approved therapeutic selectively targeting Tie2. We used a combinatorial protein
engineering approach to develop a new generation of angiopoietin (Ang)2-derived
Tie2 antagonists as potential cancer therapeutics and as tools to study
angiogenesis. The construct for designing a yeast surface display (YSD) library
of potential antagonists was an Ang2 binding domain (Ang2-BD) that retains Tie2
binding ability but prevents ligand multimerization and receptor dimerization and
activation. This mutant library was then screened by quantitative high-throughput
flow cytometric sorting to identify Ang2-BD variants with increased expression,
stability and affinity to Tie2. The selected variants were recombinantly
expressed and showed high affinity to soluble and cellular Tie2 and strongly
inhibited both Tie2 phosphorylation and endothelial capillary tube formation and
cell invasion compared to the parental Ang2-BD. The significance of the study
lies in the insight it provides into the sequence-structure-function
relationships and mechanism of action of the antagonistic Ang mutants. The
approach of using a natural protein ligand as a molecular scaffold for
engineering high-affinity agents can be applied to other ligands to create
functional protein antagonists against additional biomedical targets.
PMID- 28422725
TI - MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by
inhibiting mTOR signaling pathway and expression of MDR1.
AB - Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different
human malignancies, however, little is known about miR-199a-3p in
cholangiocarcinoma cells. In this study, we demonstrate the essential role and
mechanism of miR-199a-3p in regulating cisplatin sensitivity in
cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that
expression of miR-199a-3p was positively correlated with cisplatin sensitivity in
cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the
proliferation rate and increase apoptosis of cholangiocarcinoma cells in the
presence of cisplatin, while miR-199a-3p inhibition had the opposite effect.
Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that
miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced
the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue
experiments proved that miR-199a-3p could increase the cisplatin sensitivity of
cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also
found that miR-199a-3p overexpression could reduce cisplatin induced MDR1
expression by decreasing the synthesis and increasing the degradation of MDR1,
thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In
conclusion, miR-199a-3p could increase cisplatin sensitivity of
cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling
pathway and decreasing the expression of MDR1.
PMID- 28422726
TI - Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by
deregulating a c-src/FAK-associated signaling pathway.
AB - Recent studies have shown that increased syndecan-1 (SDC1) expression in human
glioma is associated with higher tumor grades and poor prognoses, but its
oncogenic functions and the underlying molecular mechanisms remain unknown. Here,
we examined SDC1 expression in datasets from The Cancer Genome Atlas and the
National Center for Biotechnology Information Gene Expression Omnibus. Elevated
SDC1 expression in glioma was closely associated with increases in tumor
progression and shorter survival. We also examined SDC1 expression and evaluated
the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown
attenuated proliferation and invasion by glioma cells and markedly decreased PCNA
and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown
suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased
phosphorylation of the c-src/FAK complex and its downstream signaling molecules,
Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic
target in the treatment of glioma.
PMID- 28422727
TI - MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer
cells through a Sp1 negative feedback loop.
AB - MicroRNAs have recently emerged as regulators of many biological processes
including cell proliferation, development and differentiation. This study
identified that miR-22 was statistically decreased in colorectal cancer clinical
specimens and highly metastatic cell lines. Moreover, low miR-22 expression was
associated with tumor metastasis, advanced clinical stage and relapse. Consistent
with clinical observations, miR-22 significantly suppressed the ability of
colorectal cancer cells to growth and metastasize in vitro and in vivo. Sp1 was
validated as a target of miR-22, and ectopic expression of Sp1 compromised the
inhibitory effects of miR-22. In addition, Sp1 repressed miR-22 transcription by
binding to the miR-22 promoter, hence forming a negative feedback loop. Further
study has shown that miR-22 suppresses the activity of PTEN/AKT pathway by Sp1.
Our present results implicate the newly indentified miR-22/Sp1/PTEN/AKT axis
might represent a potential therapeutic target for colorectal cancer.
PMID- 28422728
TI - Antimicrobial peptides with selective antitumor mechanisms: prospect for
anticancer applications.
AB - In the last several decades, there have been significant advances in anticancer
therapy. However, the development of resistance to cancer drugs and the lack of
specificity related to actively dividing cells leading to toxic side effects have
undermined these achievements. As a result, there is considerable interest in
alternative drugs with novel antitumor mechanisms. In addition to the recent
approach using immunotherapy, an effective but much cheaper therapeutic option of
pharmaceutical drugs would still provide the best choice for cancer patients as
the first line treatment. Ribosomally synthesized cationic antimicrobial peptides
(AMPs) or host defense peptides (HDP) display broad-spectrum activity against
bacteria based on electrostatic interactions with negatively charged lipids on
the bacterial surface. Because of increased proportions of phosphatidylserine
(negatively charged) on the surface of cancer cells compared to normal cells,
cationic amphipathic peptides could be an effective source of anticancer agents
that are both selective and refractory to current resistance mechanisms. We
reviewed herein the prospect for AMP application to cancer treatment, with a
focus on modes of action of cationic AMPs.
PMID- 28422729
TI - The relevance of a low JAK2V617F allele burden in clinical practice: a
monocentric study.
AB - Since low JAK2V617F allele burden (AB) has been detected also in healthy
subjects, its clinical interpretation may be challenging in patients with chronic
myeloproliferative neoplasms (MPNs). We tested 1087 subjects for JAK2V617F
mutation on suspicion of hematological malignancy. Only 497 (45.7%) patients were
positive. Here we present clinical and laboratory parameters of a cohort of
35/497 patients with an AB <= 3%.Overall, 22/35 (62.9%) received a WHO-defined
diagnosis of MPN and in 14/35 cases (40%) diagnosis was supported by bone marrow
(BM) histology (''Histology-based'' diagnosis). In patients that were unable or
refused to perform BM evaluation, diagnosis relied on prospective clinical
observation (12 cases, 34.3%) and molecular monitoring (6 cases, 17.1%)
(''Clinical-based'' or ''Molecular-based'' diagnosis, respectively). In 11/35
(31.4%) patients, a low JAK2V617F AB was not conclusive of MPN. The probability
to have a final hematological diagnosis (ET/PV/MF) was higher in patients with
thrombocytosis than in patients with polyglobulia (73.7% vs 57.1%, respectively).
The detection of AB >= 0.8% always corresponded to an overt MPN phenotype. The
repetition of JAK2V617F evaluation over time timely detected the spontaneous
expansion (11 cases) or reduction (4 cases) of JAK2V617F-positive clones and
significantly oriented the diagnostic process.Our study confirms that histology
is relevant to discriminate small foci of clonal hematopoiesis with uncertain
clinical significance from a full blown disease. Remarkably, our data suggest
that a cut-off of AB >= 0.8% is very indicative for the presence of a MPN.
Monitoring of the AB over time emerged as a convenient and non-invasive method to
assess clonal hematopoiesis expansion.
PMID- 28422731
TI - Risk of osteoporosis and pathologic fractures in cancer patients who underwent
hematopoietic stem cell transplantation: a nationwide retrospective cohort study.
AB - BACKGROUND: Long-term data on post-hematopoietic stem cell transplantation (HSCT)
osteoporosis and fracture are limited. This study evaluated the long-term risk of
osteoporosis and fracture in cancer patients who underwent HSCT. RESULTS: The
incidence density rate of osteoporosis was 12.5 per 1000 person-years in the HSCT
group, which was significantly higher than that in the non-HSCT group (5.65 per
1000 person-years) after adjustment for associated factors and consideration of
competing risk factors (adjusted subhazard ratio, 1.48; 95% confidence interval,
1.06-2.07). The incidence density rate of fracture was 4.89 per 1000 person-years
in the HSCT group, and the risk of fracture was 1.40 times higher in the HSCT
group than in the non-HSCT group (95% confidence interval, 0.83-2.40). The
vertebra was the most common site of fracture after HSCT (68.4%). The risk of
osteoporosis and fracture significantly increased in post-HSCT patients with both
hematological malignancies and solid tumors. Both autologous and allogeneic HSCTs
increased the risk of osteoporosis, whereas only autologous HSCT recipients had
an increased risk of fracture. MATERIALS AND METHODS: This nationwide
retrospective cohort study analyzed data from Taiwan's National Health Insurance
Research Database. We identified an HSCT group comprising 1040 cancer patients
who underwent HSCT during 2000-2008 and a non-HSCT group comprising 4160
propensity score-matched cancer patients who did not undergo HSCT. All patients
were followed up until the occurrence of osteoporosis; fracture; December 31,
2011; or withdrawal from the insurance program. CONCLUSIONS: HSCT recipients have
an increased risk of osteoporosis.
PMID- 28422730
TI - miR-133b, a particular member of myomiRs, coming into playing its unique
pathological role in human cancer.
AB - MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role
in regulating gene expression at posttranscriptional level, by which it can
mediate various types of physiological and pathological process in normal
developmental progress and human disease, including cancer. The microRNA-133b
originally defined as canonical muscle-specific microRNAs considering their
function to the development and health of mammalian skeletal and cardiac muscles,
but new findings coming from our group and others revealed that miR-133b have
frequently abnormal expression in various kinds of human cancer and its complex
complicated regulatory networks affects the tumorigenicity and development of
malignant tumors. Very few existing reviews on miR-133b, until now, are
principally about its role in homologous cluster (miR-1, -133 and -206s),
however, most of constantly emerging new researches now are focused mainly on one
of them, so In this article, to highlight the unique pathological role of miR
133b playing in tumor, we conduct a review to summarize the current understanding
about one of the muscle-specific microRNAs, namely miR-133b, acting in human
cancer. The review focused on the following four aspects: the overview of miR
133b, the target genes of miR-133b involved in human cancer, the expression of
miR-133b and regulatory mechanisms leading to abnormal expression of miR-133b.
PMID- 28422733
TI - The transcriptional STAT3 is a potential target, whereas transcriptional
STAT5A/5B/6 are new biomarkers for prognosis in human breast carcinoma.
AB - Signal Transducer and Activators of Transcription (STAT) is a set of
transcription factors, involved in diverse cellular functions. Evidences from
cell lines, mouse models and human tissues implicate these transcription factors
in the oncogenesis of breast cancer. However, the diverse expression patterns and
prognostic values of 7 STATs remain to be elucidated. In the current study, we
mined the transcriptional and survival data of STATs in patients with breast
carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and
cBioPortal. It was found that STAT1/2 were up-regulated, whereas STAT3/4/5A/5B
were down-regulated in BC patients compared with the normal tissues. The
expressions of STAT5A/5B/6 were correlated with decreased levels of histological
differentiation. In survival analyses through the Kaplan-Meier plotter database,
high transcription levels of STAT2/4/5A/5B/6 were associated with better relapse
free survival (RFS) in all BC patients. Conversely, high STAT3 predicted shorter
RFS in BC patients, suggesting that STAT3 is potential targets for precision
therapy to BC patients. These data also provided STAT5A/5B/6 as new biomarker for
BC prognosis.
PMID- 28422732
TI - Molecular and serologic markers of HPV 16 infection are associated with local
recurrence in patients with oral cavity squamous cell carcinoma.
AB - Human papillomavirus (HPV) infections predict mortality in Taiwanese patients
with oral cavity squamous cell carcinoma (OCSCC). To address their prognostic
significance for local recurrence (LR), in this retrospective cohort study we
investigated different serologic and molecular markers of HPV 16 infection in 85
consecutive patients with primary OCSCC who received standard treatment and had
their sera stored before treatment. Resected tumor specimens were examined with
PCR-based assays for HPV 16 E6/E7 mRNA expression. Sera were tested with
suspension arrays for the presence of HPV-specific antibodies using synthetic L1
and E6 peptides as well as a synthetic E7 protein. HPV 16 E6/E7 mRNA, anti-L1,
anti-E6, and anti-E7 antibodies tested positive in 12%, 25%, 38%, and 41% of the
study patients, respectively. Multivariate analysis identified pathological
T3/T4, E6/E7 mRNA, and anti-E7 antibodies as independent risk factors for LR,
whereas anti-E6 antibodies were an independent protective factor. In patients
with >= 3 (high-risk group), 2 (intermediate-risk), and <= 1 (low-risk)
independent risk factors (predictors), the 5-year LR rates were 75%, 42%, and 4%,
respectively. Results were validated in an independent cohort. Together, our
preliminary data indicate that HPV 16 infections as well as low and high serum
levels of anti-E6 and anti-E7 antibodies, respectively, can serve as biomarkers
of LR in patients with OCSCC, whereas the clinical usefulness of anti-HPV 16
antibodies for risk stratification of newly diagnosed cases deserves further
scrutiny.
PMID- 28422734
TI - Silencing of karyopherin alpha2 inhibits cell growth and survival in human
hepatocellular carcinoma.
AB - Karyopherin alpha2 (KPNA2), involved in nucleocytoplasmic transport, has been
reported to be upregulated in hepatocellular carcinoma and considered as a
biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions
in hepatocellular carcinogenesis are still lacking. Our study examine the roles
and related molecular mechanisms of KPNA2 in hepatocellular carcinoma
development. Results show that KPNA2 knockdown inhibited the proliferation and
growth of hepatocellular carcinoma cells in vitro and in vivo. KPNA2 knockdown
also inhibited colony formation ability, induced cell cycle arrest and cellular
apoptosis in two hepatocellular carcinoma cell lines, HepG2 and SMMC-7721.
Furthermore, gene expression microarray analysis in HepG2 cells with KPNA2
knockdown revealed that critical signaling pathways involved in cell
proliferation and survival were deregulated. In conclusion, this study provided
systematic evidence that KPNA2 was an essential factor promoting hepatocellular
carcinoma and unraveled potential molecular pathways and networks underlying
KPNA2-induced hepatocellular carcinogenesis.
PMID- 28422736
TI - Identification of MAP kinase pathways as therapeutic targets in gallbladder
carcinoma using targeted parallel sequencing.
AB - The aim of this study was to profile somatic mutation spectrum in gallbladder
cancers (GBCs), and determine the role of MAP kinase pathway in GBC by a series
of in vitro and in vivo studies. We performed targeted massively parallel
sequencing of DNA isolated from GBCs and matched blood from 14 GBC patients to
search for mutations in 504 genes commonly altered in human cancers. We
identified recurrent mutations enriched in several major signaling pathways
including MAP kinase, Wnt/beta-catenin and NF-kappaB pathways.
Immunohistochemistry analysis further validated overactivation of MAP kinase and
Wnt pathways in a panel of GBC samples. By treating GBC cells with MEK inhibitor
trametinib, we found that trametinib not only dramatically inhibited the activity
of MAPK/ERK pathway, but also blocked the Wnt/beta-catenin signaling through
decreasing beta-catenin expression or suppressing nucleus translocation of beta
catenin. Moreover, trametinib inhibited the proliferation of GBC cell in a dose-
and time-dependent manner, induced GBC cell apoptosis, and inhibited GBC cell
migration and invasion. Growth of xenograft tumors derived from GBC cell line NOZ
in nude mice was also significantly inhibited by trametinib. Our data highlight
the critical role of MAP kinase pathways in GBC pathogenesis, and may represent
therapeutic targets for this cancer.
PMID- 28422735
TI - Expression of embryonal stem cell transcription factors in breast cancer: Oct4 as
an indicator for poor clinical outcome and tamoxifen resistance.
AB - The transcription factors of embryonic stem cells, such as Oct4, Sox2, Nanog,
Bmi1, and Klf4, are known to be associated with stemness, epithelial-mesenchymal
transition and aggressive tumor behavior. This study was designed to evaluate the
clinicopathological significance of their expression in breast cancer.
Immunohistochemistry for Oct4, Sox2, Nanog, Bmi1, and Klf4 was performed in 319
cases of invasive breast cancer. The relationship between the expression of these
markers and clinicopathologic features of the tumors, including breast cancer
stem cell phenotype and epithelial-mesenchymal transition marker expression, and
their prognostic value in breast cancer, were analyzed. Expression of Oct4 and
Sox2 was commonly associated with high histologic grade and high Ki-67 index in
the whole group and in the hormone receptor-positive subgroup. On the other hand,
expression of Nanog, Bmi1, and Klf4 was inversely correlated with aggressive
features of the breast cancer. Oct4 expression was associated with ALDH1
expression but not with epithelial-mesenchymal transition marker expression. In
survival analysis, Oct4 expression was independently associated with poor
prognosis in the whole group and in the hormone receptor-positive subgroup, but
not in hormone receptor-negative subgroup. Particularly, Oct4 expression was
associated with poor clinical outcome in patients with hormone receptor-positive
breast cancer treated with tamoxifen. Our results indicate that Oct4 expression
is associated with aggressive features, ALDH1 expression, tamoxifen resistance
and poor clinical outcomes in hormone receptor-positive breast cancer, and thus
may be useful as a predictive and prognostic marker in this subgroup of breast
cancer.
PMID- 28422737
TI - Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9
mediated genome editing.
AB - Tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are effective
against lung adenocarcinomas harboring epidermal growth factor receptor (EGFR)
mutations. However, cancer cells can develop resistance to these agents with
prolonged exposure; in over 50% of cases, this is attributable to the EGFR T790M
mutation. Moreover, additional resistance mutations can arise with the use of new
drugs. Cancer cell lines with specific mutations can enable the study of
resistance mechanisms. In this study, we introduced the EGFR T790M mutation into
the PC9 human lung cancer cell line-which has a deletion in exon 19 of the EGFR
gene-by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated (Cas)9-mediated genome editing. EGFR pyrosequencing and peptide
nucleic acid clamping revealed that PC9 cells with EGFR T790M generated by
CRISPR/Cas 9 had a higher T790M mutation rate than those with the same mutation
generated by long-term exposure to gefitinib (PC9-G); moreover, resistance to
gefitinib in these clones was higher than that in PC9-G cells. The clones were
also highly sensitive to the 3rd-generation EGFR TKI AZD9291, which is cytotoxic
to lung cancer cells with EGFR T790M. The CRISPR/Cas9 programmable nuclease
system can be used to generate various cancer cell lines with specific mutations
that can facilitate studies on resistance mechanisms and drug efficacy.
PMID- 28422738
TI - Peripheral zone volume ratio (PZ-ratio) is relevant with biopsy results and can
increase the accuracy of current diagnostic modality.
AB - The current diagnostic modality of prostate cancer based on prostate specific
antigen (PSA) and systematic biopsy is far from ideal in terms of over-diagnosing
indolent prostate cancer and missing significant ones. Thus we integrated the
peripheral zone volume ratio (PZ-ratio) for diagnostic refinement. This
retrospective study included 247 consecutive patients who underwent initial
transrectal ultrasound-guided systematic prostate biopsy from April 2014 to
November 2015. Prostate volume was determined by semi-automatic contour on axial
T2 weighted magnetic resonance imaging (MRI). PZ-ratio was inversely correlated
with age (r = -0.36, p <0.0001). Adding PZ-ratio and MRI findings to the current
predictive model (age, PSA density, percent-free PSA) significantly increased
diagnostic accuracy in all patients (AUC: 0.871 vs. 0.812, p = 0.0059), but not
in patient subgroup with PSA 4-10 ng/ml (AUC: 0.863 vs. 0.803, p = 0.12). The new
model also significantly reduced the number of unnecessary biopsies while missing
less significant cancers at a probability threshold of 25%. PZ-ratio is a
potential tool in predicting biopsy results, and when added alone or in
combination with MRI findings, the diagnostic accuracy can be further enhanced.
PMID- 28422739
TI - Diagnostic role of Wnt pathway gene promoter methylation in non small cell lung
cancer.
AB - Wnt signal pathway genes are known to be involved with cancer development. Here
we tested the hypothesis whether DNA methylation of genes part of the Wnt
signaling pathway could help the diagnosis of non-small cell lung cancer (NSCLC).
The methylation levels of SFRP1, SFRP2, WIF1 and PRKCB in 111 NSCLC patients were
evaluated by quantitative methylation-specific PCR (qMSP). Promoter methylation
levels of four candidate genes were significantly higher in tumor tissues
compared with the adjacent tissues. SFRP1, SFRP2 and PRKCB genes were all shown
to be good predictors of NSCLC risk (SFRP1: AUC = 0.711; SFRP2: AUC = 0.631;
PRKCB: AUC = 0.650). The combined analysis showed that the methylation status of
the four genes had a sensitivity of 70.3% and a specificity of 73.9% in the
prediction of NSCLC risk for study cohort. A higher diagnostic value with an AUC
of 0.945 (95% CI: 0.923-0.967, sensitivity: 90.6%, specificity: 93.0%) was found
in TCGA cohort. In addition, SFRP1 and SFRP2 hypermethylation events were
specific to male patients. Further TCGA data mining analysis suggested that
SFRP1_cg15839448, SFRP2_cg05774801, and WIF1_cg21383810 were inversely associated
with the host gene expression. Moreover, GEO database analysis showed that 5'-Aza
deoxycytidine was able to upregulate gene expression in several lung cancer cell
lines. Subsequent dual-luciferase reporter assay showed a crucial regulatory
function of PRKCB promoter. In summary, our study showed that a panel of Wnt
signal pathway genes (SFRP1, SFRP2, WIF1 and PRKCB) had the potential as
methylation biomarkers in the diagnosis of NSCLC.
PMID- 28422740
TI - Involvement of miR-106b in tumorigenic actions of both prolactin and estradiol.
AB - Prolactin promotes a variety of cancers by an array of different mechanisms.
Here, we have investigated prolactin's inhibitory effect on expression of the
cell cycle-regulating protein, p21. Using a miRNA array, we identified a number
of miRNAs upregulated by prolactin treatment, but one in particular that was
strongly induced by prolactin and predicted to bind to the 3'UTR of p21 mRNA, miR
106b. By creating a p21 mRNA 3'UTR-luciferase mRNA construct, we demonstrated
degradation of the construct in response to prolactin in human breast, prostate
and ovarian cancer cell lines. Increased expression of miR-106b replicated, and
anti-miR-106b counteracted, the effects of prolactin on degradation of the 3'UTR
construct, p21 mRNA levels, and cell proliferation in breast (T47D) and prostate
(PC3) cancer cells. Increased expression of miR-106b also stimulated migration of
the very epithelioid T47D cell line. By contrast, anti-miR-106b dramatically
decreased expression of the mesenchymal markers, SNAIL-2, TWIST-2, VIMENTIN, and
FIBRONECTIN. Using signaling pathway inhibitors and the 3'UTR construct,
induction of miR-106b by prolactin was determined to be mediated through the
MAPK/ERK and PI3K/Akt pathways and not through Jak2/Stat5 in both T47D and PC3
cells. Prolactin activation of MAPK/ERK and PI3K/Akt also activates ERalpha in
the absence of an ERalpha ligand. 17beta-estradiol promoted degradation of the
construct in both cell lines and pre-incubation in the estrogen antagonist,
Fulvestrant, blocked the ability of both prolactin and 17beta-estradiol to induce
the construct-degrading activity. Together, these data support a convergence of
the prolactin and 17beta-estradiol miR-106b-elevating signaling pathways at
ERalpha.
PMID- 28422741
TI - Calmodulin promotes matrix metalloproteinase 9 production and cell migration by
inhibiting the ubiquitination and degradation of TBC1D3 oncoprotein in human
breast cancer cells.
AB - The hominoid oncoprotein TBC1D3 enhances growth factor (GF) signaling and GF
signaling, conversely, induces the ubiquitination and subsequent degradation of
TBC1D3. However, little is known regarding the regulation of this degradation,
and the role of TBC1D3 in the progression of tumors has also not been defined. In
the present study, we demonstrated that calmodulin (CaM), a ubiquitous cellular
calcium sensor, specifically interacted with TBC1D3 in a Ca2+-dependent manner
and inhibited GF signaling-induced ubiquitination and degradation of the
oncoprotein in both cytoplasm and nucleus of human breast cancer cells. The CaM
interacting site of TBC1D3 was mapped to amino acids 157~171, which comprises two
1-14 hydrophobic motifs and one lysine residue (K166). Deletion of these motifs
was shown to abolish interaction between TBC1D3 and CaM. Surprisingly, this
deletion mutation caused inability of GF signaling to induce the ubiquitination
and subsequent degradation of TBC1D3. In agreement with this, we identified
lysine residue 166 within the CaM-interacting motifs of TBC1D3 as the actual site
for the GF signaling-induced ubiquitination using mutational analysis. Point
mutation of this lysine residue exhibited the same effect on TBC1D3 as the
deletion mutant, suggesting that CaM inhibits GF signaling-induced degradation of
TBC1D3 by occluding its ubiquitination at K166. Notably, we found that TBC1D3
promoted the expression and activation of MMP-9 and the migration of MCF-7 cells.
Furthermore, interaction with CaM considerably enhanced such effect of TBC1D3.
Taken together, our work reveals a novel model by which CaM promotes cell
migration through inhibiting the ubiquitination and degradation of TBC1D3.
PMID- 28422742
TI - Multi-omics study revealing the complexity and spatial heterogeneity of tumor
infiltrating lymphocytes in primary liver carcinoma.
AB - Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC).
However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which
reflects one dimension of a tumor's spatial heterogeneity, and the relationship
between TIL diversity, local immune response and mutation burden remain
unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene
expression profiling analysis and whole-exome sequencing in parallel on five
regions of each tumor and on matched adjacent normal tissues and peripheral blood
from five PLC patients. A significantly higher cumulative frequency of the top
250 most abundant TIL clones was observed in tumors than in peripheral blood.
Besides, overlap rates of T cell receptor (TCR) repertoire for intratumor
comparisons, significant higher than those for tumor-adjacent normal tissue
comparisons and tumor-blood comparisons, which provide evidence for antigen
driven clonal expansion in PLC. Analysis of the percentage of ubiquitous TCR
sequences, regional frequencies of each clone and TIL diversity suggested TIL
clones varying between distinct regions of the same tumor, which indicated weak
TCR repertoire similarity within a single tumor. Furthermore, correlation
analysis revealed that TIL diversity significantly correlated with the expression
of immune response genes rather than the mutation load. We conclude that
intratumoural T-cell clones are spatially heterogeneous, which can lead to
underestimate the immune profile of PLC from a single biopsy sample and may
present challenge to adoptive cell therapy using autologous TILs. TIL diversity
provides a reasonable explanation for the degree of immune response, implied TIL
diversity can serve as a surrogate marker to monitor the effect of immunotherapy.
PMID- 28422746
TI - Integrating nanohybrid membranes of reduced graphene oxide: chitosan: silica sol
gel with fiber optic SPR for caffeine detection.
AB - Caffeine is the most popular psychoactive drug consumed in the world for
improving alertness and enhancing wakefulness. However, caffeine consumption
beyond limits can result in lot of physiological complications in human beings.
In this work, we report a novel detection scheme for caffeine integrating
nanohybrid membranes of reduced graphene oxide (rGO) in chitosan modified silica
sol gel (rGO: chitosan: silica sol gel) with fiber optic surface plasmon
resonance. The chemically synthesized nanohybrid membrane forming the sensing
route has been dip coated over silver coated unclad central portion of an optical
fiber. The sensor works on the mechanism of modification of dielectric function
of sensing layer on exposure to analyte solution which is manifested in terms of
red shift in resonance wavelength. The concentration of rGO in polymer network of
chitosan and silica sol gel and dipping time of the silver coated probe in the
solution of nanohybrid membrane have been optimized to extricate the supreme
performance of the sensor. The optimized sensing probe possesses a reasonably
good sensitivity and follows an exponentially declining trend within the entire
investigating range of caffeine concentration. The sensor boasts of an
unparalleled limit of detection value of 1.994 nM and works well in concentration
range of 0-500 nM with a response time of 16 s. The impeccable sensor methodology
adopted in this work combining fiber optic SPR with nanotechnology furnishes a
novel perspective for caffeine determination in commercial foodstuffs and
biological fluids.
PMID- 28422745
TI - Targeting of the breast cancer microenvironment with a potent and linkable
oxindole based antiangiogenic small molecule.
AB - The clinical efficacy of antiangiogenic small molecules (e.g., sunitinib) in
breast carcinoma has largely failed with substantial off-target toxicity. We
rationally designed and evaluated preclinically a novel sunitinib analogue, SAP,
with favourable pharmacological properties and the ability to be readily
conjugated to a targeting peptide or antibody for active tumour targeting.SAP was
evaluated in silico and in vitro in order to verify target engagement (e.g.,
VEGFR2). Pharmacokinetic and biodistribution parameters were determined in mice
using LC-MS/MS. SAP efficacy was tested in two breast cancer xenograft and two
syngeneic animal models and pharmacodynamic evaluation was accomplished using
phosphokinase assays and immunohistochemistry. Cardiac and blood toxicity of SAP
were also monitored.SAP retained the antiangiogenic and cytotoxic properties of
the parental molecule with an increased blood exposure and tumor accumulation
compared to sunitinib. SAP proved efficacious in all animal models. Tumors from
SAP treated animals had significantly decreased Ki-67 and CD31 markers and
reduced levels of phosphorylated AKT, ERK and S6 compared to vehicle treated
animals. In mice dosed with SAP there was negligible hematotoxicity, while
cardiac function measurements showed a reduction in the percentage left
ventricular fractional shortening compared to vehicle treated animals.In
conclusion, SAP is a novel rationally designed conjugatable small antiangiogenic
molecule, efficacious in preclinical models of breast cancer.
PMID- 28422747
TI - Controlled multiple neutral planes by low elastic modulus adhesive for flexible
organic photovoltaics.
AB - To protect brittle layers in organic photovoltaic devices, the mechanical neutral
plane strategy can be adopted through placing the brittle functional materials
close to the neutral plane where stress and strain are zero during bending.
However, previous research has been significantly limited in the location and
number of materials to protect through using a single neutral plane. In this
study, multiple neutral planes are generated using low elastic modulus adhesives
and are controlled through quantitative analyses in order to protect the multiple
brittle materials at various locations. Moreover, the protection of multiple
brittle layers at various locations under both concave and convex bending
directions is demonstrated. Multilayer structures that have soft adhesives are
further analyzed using the finite element method analysis in order to propose
guidelines for structural design when employing multiple neutral planes.
PMID- 28422748
TI - Therapeutic inhibition of soluble brain TNF promotes remyelination by increasing
myelin phagocytosis by microglia.
AB - Multiple sclerosis (MS) is an inflammatory CNS demyelinating disease in which
remyelination largely fails. Transmembrane TNF (tmTNF) and TNF receptor 2 are
important for remyelination in experimental MS models, but it is unknown whether
soluble TNF (solTNF), a major proinflammatory factor, is involved in regeneration
processes. Here, we investigated the specific contribution of solTNF to
demyelination and remyelination in the cuprizone model. Treatment with XPro1595,
a selective inhibitor of solTNF that crosses the intact blood-brain barrier
(BBB), in cuprizone-fed mice did not prevent toxin-induced oligodendrocyte loss
and demyelination, but it permitted profound early remyelination due to improved
phagocytosis of myelin debris by CNS macrophages and prevented disease-associated
decline in motor performance. The beneficial effects of XPro1595 were absent in
TNF-deficient mice and replicated in tmTNF-knockin mice, showing that tmTNF is
sufficient for the maintenance of myelin and neuroprotection. These findings
demonstrate that solTNF inhibits remyelination and repair in a cuprizone
demyelination model and suggest that local production of solTNF in the CNS might
be one reason why remyelination fails in MS. These findings also suggest that
disinhibition of remyelination by selective inhibitors of solTNF that cross the
BBB might represent a promising approach for treatment in progressive MS.
PMID- 28422749
TI - Obesity-induced hepatic steatosis is mediated by endoplasmic reticulum stress in
the subfornical organ of the brain.
AB - Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation
of hepatic triglycerides, is a growing health epidemic. While ER stress in the
liver has been implicated in the development of NAFLD, the role of brain ER
stress - which is emerging as a key contributor to a number of chronic diseases
including obesity - in NAFLD remains unclear. These studies reveal that chemical
induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in
mice. Conversely, pharmacological reductions in brain ER stress in diet-induced
obese mice rescued NAFLD independent of body weight, food intake, and adiposity.
Evaluation of brain regions involved revealed robust activation of ER stress
biomarkers and ER ultrastructural abnormalities in the circumventricular
subfornical organ (SFO), a nucleus situated outside of the blood-brain-barrier,
in response to high-fat diet. Targeted reductions in SFO-ER stress in obese mice
via SFO-specific supplementation of the ER chaperone 78-kDa glucose-regulated
protein ameliorated hepatomegaly and hepatic steatosis without altering body
weight, food intake, adiposity, or obesity-induced hypertension. Overall, these
findings indicate a novel role for brain ER stress, notably within the SFO, in
the pathogenesis of NAFLD.
PMID- 28422750
TI - Differential expression of GPR15 on T cells during ulcerative colitis.
AB - G protein-coupled receptor 15 (GPR15) was recently highlighted as a colon-homing
receptor for murine and human CD4+ T cells. The aim of this study was to explore
the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and
effector T cells (Teffs), and to determine whether GPR15 is the driver for the
migration of T cells to the colon during ulcerative colitis (UC). In the
peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell
subsets produced less IFN-gamma and IL-4 but more IL-17 after stimulation and
showed a higher migration activity compared with GPR15-CD4+ T cells. In UC
patients, GPR15 expression was increased on Tregs in the peripheral blood but not
on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on
colonic T cells of UC patients in noninflamed biopsies but not in inflamed
biopsies. The differential expression of GPR15 in UC patients was accompanied by
a significant reduction of bacterial immunoregulatory metabolites in the feces.
In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which
may have implications for the development of therapeutic approaches to target T
cell trafficking to the colon.
PMID- 28422751
TI - Twelve-year survival and immune correlates in dendritic cell-vaccinated melanoma
patients.
AB - BACKGROUND: Reports on long-term (>=10 years) effects of cancer vaccines are
missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous
melanoma patients to further explore the immunogenicity of our DC vaccine and to
establish its long-term toxicity and clinical benefit after a planned 10-year
followup. METHODS: Monocyte-derived DCs matured by TNFalpha, IL-1beta, IL-6, and
PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides
were injected intradermally in high doses over 2 years. We performed serial
immunomonitoring in all 53 evaluable patients. RESULTS: Vaccine-specific immune
responses including high-affinity, IFNgamma-producing CD4+ and lytic
polyfunctional CD8+ T cells were de novo induced or boosted in most patients.
Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not
further enhance such immune responses, while keyhole limpet hemocyanin (KLH)
pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses - notably,
their longevity. An unexpected 19% of nonresectable metastatic melanoma patients
are still alive after 11 years, a survival rate similar to that observed in
ipilimumab-treated patients and achieved without any major (>grade 2) toxicity.
Survival correlated significantly with the development of intense vaccine
injection site reactions, and with blood eosinophilia after the first series of
vaccinations, suggesting that prolonged survival was a consequence of DC
vaccination. CONCLUSIONS: Long-term survival in advanced melanoma patients
undergoing DC vaccination is similar to ipilimumab-treated patients and occurs
upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine
injection site reactions occurring after the initial vaccinations. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00053391. FUNDING: European Community, Sixth
Framework Programme (Cancerimmunotherapy LSHC-CT-2006-518234; DC-THERA LSHB-CT
2004-512074), and German Research Foundation (CRC 643, C1, Z2).
PMID- 28422752
TI - T-bet+ B cells are induced by human viral infections and dominate the HIV gp140
response.
AB - Humoral immunity is critical for viral control, but the identity and mechanisms
regulating human antiviral B cells are unclear. Here, we characterized human B
cells expressing T-bet and analyzed their dynamics during viral infections. T
bet+ B cells demonstrated an activated phenotype, a distinct transcriptional
profile, and were enriched for expression of the antiviral immunoglobulin
isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and
vaccinia virus vaccinations and also during early acute HIV infection. Viremic
HIV-infected individuals maintained a large T-bet+ B cell population during
chronic infection that was associated with increased serum and cell-associated
IgG1 and IgG3 expression. The HIV gp140-specific B cell response was dominated by
T-bet-expressing memory B cells, and we observed a concomitant biasing of gp140
specific serum immunoglobulin to the IgG1 isotype. These findings suggest that T
bet induction promotes antiviral immunoglobulin isotype switching and development
of a distinct T-bet+ B cell subset that is maintained by viremia and coordinates
the HIV Env-specific humoral response.
PMID- 28422753
TI - Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary
aldosteronism.
AB - BACKGROUND: Adrenal aldosterone excess is the most common cause of secondary
hypertension and is associated with increased cardiovascular morbidity. However,
adverse metabolic risk in primary aldosteronism extends beyond hypertension, with
increased rates of insulin resistance, type 2 diabetes, and osteoporosis, which
cannot be easily explained by aldosterone excess. METHODS: We performed mass
spectrometry-based analysis of a 24-hour urine steroid metabolome in 174 newly
diagnosed patients with primary aldosteronism (103 unilateral adenomas, 71
bilateral adrenal hyperplasias) in comparison to 162 healthy controls, 56
patients with endocrine inactive adrenal adenoma, 104 patients with mild
subclinical, and 47 with clinically overt adrenal cortisol excess. We also
analyzed the expression of cortisol-producing CYP11B1 and aldosterone-producing
CYP11B2 enzymes in adenoma tissue from 57 patients with aldosterone-producing
adenoma, employing immunohistochemistry with digital image analysis. RESULTS:
Primary aldosteronism patients had significantly increased cortisol and total
glucocorticoid metabolite excretion (all P < 0.001), only exceeded by
glucocorticoid output in patients with clinically overt adrenal Cushing syndrome.
Several surrogate parameters of metabolic risk correlated significantly with
glucocorticoid but not mineralocorticoid output. Intratumoral CYP11B1 expression
was significantly associated with the corresponding in vivo glucocorticoid
excretion. Unilateral adrenalectomy resolved both mineralocorticoid and
glucocorticoid excess. Postoperative evidence of adrenal insufficiency was found
in 13 (29%) of 45 consecutively tested patients. CONCLUSION: Our data indicate
that glucocorticoid cosecretion is frequently found in primary aldosteronism and
contributes to associated metabolic risk. Mineralocorticoid receptor antagonist
therapy alone may not be sufficient to counteract adverse metabolic risk in
medically treated patients with primary aldosteronism. FUNDING: Medical Research
Council UK, Wellcome Trust, European Commission.
PMID- 28422754
TI - MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial
infections.
AB - Perforin-2 is a highly conserved pore-forming protein encoded by macrophage
expressed gene 1 (MPEG1). A number of studies have shown that Perforin-2
deficient mice are unable to survive following a bacterial challenge that is
nonlethal in WT mice. There is also recent evidence that Mpeg1+/- heterozygous
mice display an intermediate killing ability compared with Mpeg1 WT and Mpeg1-/-
mice. Despite these in vivo findings, to date, no perforin-2 deficiencies have
been associated with human disease. Here, we report four patients with persistent
nontuberculous mycobacterial infection who had heterozygous MPEG1 mutations. In
vitro, neutrophils, macrophages, and B cells from these patients were unable to
kill Mycobacterium avium as efficiently as normal controls. CRISPR mutagenesis
validated the deleterious antibacterial activity of these mutations. These data
suggest that perforin-2 haploinsufficiency may contribute to human susceptibility
to infections with intracellular bacteria.
PMID- 28422755
TI - beta-Klotho deficiency protects against obesity through a crosstalk between
liver, microbiota, and brown adipose tissue.
AB - beta-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and
FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of
pharmacological FGF21 treatment including stimulation of glucose utilization and
thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on
high-fat diet in order to better understand the consequences of abrogating both
endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly,
Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy
expenditure and BAT activity. Klb-/- mice exhibited not only an increase but also
a shift in bile acid (BA) composition featured by activation of the classical
(neutral) BA synthesis pathway at the expense of the alternative (acidic)
pathway. High hepatic production of cholic acid (CA) results in a large excess of
microbiota-derived deoxycholic acid (DCA). DCA is specifically responsible for
activating the TGR5 receptor that stimulates BAT thermogenic activity. In fact,
combined gene deletion of Klb and Tgr5 or antibiotic treatment abrogating
bacterial conversion of CA into DCA both abolish DIO resistance in Klb-/- mice.
These results suggested that DIO resistance in Klb-/- mice is caused by high
levels of DCA, signaling through the TGR5 receptor. These data also demonstrated
that gut microbiota can regulate host thermogenesis via conversion of primary
into secondary BA. Pharmacologic or nutritional approaches to selectively
modulate BA composition may be a promising target for treating metabolic
disorders.
PMID- 28422756
TI - beta-catenin and PI3Kdelta inhibition expands precursor Th17 cells with
heightened stemness and antitumor activity.
AB - ICOS costimulation generates Th17 cells with durable memory responses to tumor.
Herein, we found that ICOS induces PI3K/p110delta/Akt and Wnt/beta-catenin
pathways in Th17 cells. Coinhibiting PI3Kdelta and beta-catenin altered the
biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed
less RORgammat, which, in turn, reduced their ability to secrete IL-17.
Unexpectedly, these cells were more effective (than uninhibited cells) at
regressing tumor when infused into mice, leading to long-term curative responses.
PI3Kdelta inhibition expanded precursor Th17 cells with a central memory
phenotype that expressed nominal regulatory properties (low FoxP3), while beta
catenin inhibition enhanced Th17 multifunctionality in vivo. Remarkably, upon TCR
restimulation, RORgammat and IL-17 rebounded in Th17 cells treated with PI3Kdelta
and beta-catenin inhibitors. Moreover, these cells regained beta-catenin, Tcf7,
and Akt expression, licensing them to secrete heightened IL-2, persist, and
eradicate solid tumors without help from endogenous NK and CD8 T cells. This
finding shines a light on ways to repurpose FDA-approved drugs to augment T cell
based cancer immunotherapies.
PMID- 28422757
TI - Cross-reactive dengue human monoclonal antibody prevents severe pathologies and
death from Zika virus infections.
AB - Zika virus (ZIKV) infections have been linked with neurological complications and
congenital Zika syndrome. Given the high level of homology between ZIKV and the
related flavivirus dengue virus (DENV), we investigated the level of cross
reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs
showed binding to ZIKV virions, with several exhibiting neutralizing capacities
against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to
recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved
fusion-loop peptide, a conformation-specific epitope on the E monomer, and a
quaternary epitope on the virion surface. The most potent ZIKV-neutralizing mAb
(SIgN-3C) was assessed in 2 type I interferon receptor-deficient (IFNAR-/-) mouse
models of ZIKV infection. Treatment of adult nonpregnant mice with SIgN-3C
rescued mice from virus-induced weight loss and mortality. The SIgN-3C variant
with Leu-to-Ala mutations in the Fc region (SIgN-3C-LALA) did not induce antibody
dependent enhancement (ADE) in vitro but provided similar levels of protection in
vivo. In pregnant ZIKV-infected IFNAR-/- mice, treatment with SIgN-3C or SIgN-3C
LALA significantly reduced viral load in the fetal organs and placenta and
abrogated virus-induced fetal growth retardation. Therefore, SIgN-3C-LALA holds
promise as a ZIKV prophylactic and therapeutic agent.
PMID- 28422758
TI - First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR
antibody cetuximab in advanced cancer patients.
AB - BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti
EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR
sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC).
METHODS: Utilizing a standard 3+3 design, a phase I study was designed to
determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities
(DLTs) of the regorafenib plus cetuximab combination among patients with advanced
cancer including CRC. Comprehensive genomic profiling was performed on the
exceptional responder. RESULTS: Among the 27 patients enrolled the median age was
54 years. None of 19 patients treated at dose level 1 (cetuximab i.v. 200 mg/m2
followed by 150 mg/m2 weekly + regorafenib 80 mg daily) experienced a DLT, and 2
of 5 patients treated at dose level 2 (cetuximab i.v. 200 mg/m2 followed by 150
mg/m2 weekly + regorafenib 120 mg daily) experienced a DLT (grade 3
thrombocytopenia [n = 1] and grade 3 intra-abdominal bleed [n = 1]). Most common
adverse events were grade 1 or 2 rash (20 patients). Of 24 evaluable patients, 11
(46%) patients had clinical benefit (stable disease > 6 cycles or partial
response [PR]) (CRC n = 8, one patient each with head and neck cancer, carcinoma
of unknown primary, and glioblastoma). A CRC patient, who progressed on anti-EGFR
and regorafenib, achieved a PR (46% decrease per RECIST v1.1) lasting 15 months.
Genomic profiling of an exceptional responder with response for over 27 cycles
revealed hypermutated genotype with microsatellite instability (MSI). CONCLUSION:
Regorafenib 80 mg daily plus cetuximab 200 mg/m2 loading dose, followed by 150
mg/m2 every week is the MTD/recommended phase II dose. The combination
demonstrated early signals of activity in wild-type CRC, including 1 exceptional
responder with MSI high. TRIAL REGISTRATION: clinicaltrials.gov
NCT02095054FUNDING. The University of Texas MD Anderson Cancer Center is
supported by the NIH Cancer Center Support Grant CA016672. This work was
supported in part by the Cancer Prevention Research Institute of Texas grant
RP110584 and National Center for Advancing Translational Sciences grant UL1
TR000371 (Center for Clinical and Translational Sciences).
PMID- 28422759
TI - RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces
bradycardia by disturbing the coupled clock pacemaker mechanism.
AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic
arrhythmia that manifests syncope or sudden death in children and young adults
under stress conditions. CPVT patients often present bradycardia and sino-atrial
node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN
function in two CPVT families and in a novel knock-in (KI) mouse model carrying
the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate.
Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was
slower in KI mouse SAN preparations than in WT, without any significant
alteration in the "funny" current (If ). The L-type Ca2+ current was reduced in
KI SAN cells in a [Ca2+]i-dependent way, suggesting that bradycardia was due to
disrupted crosstalk between the "voltage" and "Ca2+" clock, and the mechanisms of
pacemaking was induced by aberrant spontaneous RyR2- dependent Ca2+ release. This
finding was consistent with a higher Ca2+ leak during diastolic periods produced
by long-lasting Ca2+ sparks in KI SAN cells. Our results uncover a mechanism for
the CPVT-causing RyR2 N-terminal mutation R420Q, and they highlight the fact that
enhancing the Ca2+ clock may slow the heart rhythm by disturbing the coupling
between Ca2+ and voltage clocks.
PMID- 28422760
TI - Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of
idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without
effective treatment, highlighting the need for identifying new targets and
treatment modalities. The pathogenesis of IPF is complex, and engaging multiple
targets simultaneously might improve therapeutic efficacy. To assess the role of
the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF
and its interaction with inducible nitric oxide synthase (iNOS) as dual
therapeutic targets, we analyzed lung fibrosis and the status of the
endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary
fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from
patients with IPF, as well as controls. In addition, we investigated the
antifibrotic efficacy in the mouse PF model of an orally bioavailable and
peripherally restricted CB1R/iNOS hybrid inhibitor. We report that increased
activity of the endocannabinoid/CB1R system parallels disease progression in the
lungs of patients with idiopathic PF and in mice with bleomycin-induced PF and is
associated with increased tissue levels of interferon regulatory factor-5.
Furthermore, we demonstrate that simultaneous engagement of the secondary target
iNOS by the hybrid CB1R/iNOS inhibitor has greater antifibrotic efficacy than
inhibition of CB1R alone. This hybrid antagonist also arrests the progression of
established fibrosis in mice, thus making it a viable candidate for future
translational studies in IPF.
PMID- 28422761
TI - Topological length of white matter connections predicts their rate of atrophy in
premanifest Huntington's disease.
AB - We lack a mechanistic explanation for the stereotyped pattern of white matter
loss seen in Huntington's disease (HD). While the earliest white matter changes
are seen around the striatum, within the corpus callosum, and in the posterior
white matter tracts, the order in which these changes occur and why these white
matter connections are specifically vulnerable is unclear. Here, we use diffusion
tractography in a longitudinal cohort of individuals yet to develop clinical
symptoms of HD to identify a hierarchy of vulnerability, where the topological
length of white matter connections between a brain area and its neighbors
predicts the rate of atrophy over 24 months. This demonstrates a new principle
underlying neurodegeneration in HD, whereby brain connections with the greatest
topological length are the first to suffer damage that can account for the
stereotyped pattern of white matter loss observed in premanifest HD.
PMID- 28422762
TI - Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to
myofibroblast transformation.
AB - Secreted modular calcium-binding protein 2 (SMOC2) belongs to the secreted
protein acidic and rich in cysteine (SPARC) family of matricellular proteins
whose members are known to modulate cell-matrix interactions. We report that
SMOC2 is upregulated in the kidney tubular epithelial cells of mice and humans
following fibrosis. Using genetically manipulated mice with SMOC2 overexpression
or knockdown, we show that SMOC2 is critically involved in the progression of
kidney fibrosis. Mechanistically, we found that SMOC2 activates a fibroblast-to
myofibroblast transition (FMT) to stimulate stress fiber formation,
proliferation, migration, and extracellular matrix production. Furthermore, we
demonstrate that targeting SMOC2 by siRNA results in attenuation of TGFbeta1
mediated FMT in vitro and an amelioration of kidney fibrosis in mice. These
findings implicate that SMOC2 is a key signaling molecule in the pathological
secretome of a damaged kidney and targeting SMOC2 offers a therapeutic strategy
for inhibiting FMT-mediated kidney fibrosis - an unmet medical need.
PMID- 28422763
TI - A modifier screen identifies DNAJB6 as a cardiomyopathy susceptibility gene.
PMID- 28422764
TI - 3D pulmospheres serve as a personalized and predictive multicellular model for
assessment of antifibrotic drugs.
PMID- 28422765
TI - Foreign Body Type Nasal Pseudocyst After Augmentation Rhinoplasty:
Histopathologically Mucin-Containing Pseudocyst.
PMID- 28422766
TI - An Immunoscore Using PD-L1, CD68, and Tumor-infiltrating Lymphocytes (TILs) to
Predict Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer.
AB - Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is
partly regulated by the immune microenvironment. We evaluated immune checkpoint
PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and
stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and
correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy
biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed
immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+
immune or tumor cells were considered positive. CD68 was positive if >40% of
tumor stroma contained CD68+ cells or atleast 50% of tumor cells showed
infiltration by CD68+ cells. Residual Cancer burden (RCB) Score of 0/I
represented excellent response to NAC and RCB II or III unfavorable response.
Thirty-five patients had RCB 0/I and 41 pts RCB II/ III. TILs>30% were present in
prechemotherapy biopsies in 19 pts of whom 14 showed RCB 0/I (P=0.0075). Twenty
seven cases were PD-L1+ and 20 had an RCB 0/I (P=0.0003). Twenty-two cases were
CD68+ of whom 18 showed RCB 0/I (P=<0.0001) There was a significant association
between TILs>30%, PD-L1+ and CD68+ expression. Using atleast one of these
immunologic parameters identified 26 of 35 patients with RCB 0/I and showed a
higher sensitivity for response prediction than TILs alone (40% vs. 74.3%). In
conclusion we demonstrate that high numbers of CD68+ monocytic/macrophage cells
and PD-L1 expression in IBC shows significant association with NAC response. An
immune biomarker profile including TILs, PD-LI and CD68 is more sensitive for NAC
response prediction than TILs alone.
PMID- 28422767
TI - Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and
inhibits metastasis through AKT-GSK-3beta and ERK1/2 signaling pathways.
AB - Pseudolaric acid B (PAB) is the most active constituent extracted from the bark
of Pseudolarix kaempferi, which has been used as an antifungal remedy in
traditional Chinese medicine. It is reported to have cytotoxicity to many tumor
cell lines. In this study, we investigated the effects of PAB against human
endometrial cancer Ishikawa cells. We found that PAB inhibited Ishikawa cell
proliferation, and induced cell apoptosis and G2/M phase arrest through a
mechanism involving AKT-GSK-3beta and ERK1/2 signaling pathways. PAB also
suppressed the Ishikawa cell adhesion, invasion, migration, and colony formation
ability by increasing the expression of E-cadherin, Ezrin, and Kiss-1, and
decreasing the expression of matrix metalloproteinase-9 and vascular endothelial
growth factor. Taken together, these data indicated that PAB can be expected to
be a novel treatment agent for endometrial cancer therapy.
PMID- 28422769
TI - Visual Outcomes and Local Control After Fractionated Stereotactic Radiotherapy
for Optic Nerve Sheath Meningioma.
AB - PURPOSE: To review the outcomes of patients with optic nerve sheath meningiomas
(ONSM) treated with fractionated stereotactic radiotherapy. METHODS: Patient
characteristics, treatment, and outcomes were analyzed for all patients with
primary and secondary ONSM treated from 2001 to 2012. Clinically significant
visual acuity change was defined as a 2-line change on the Snellen eye chart from
pre-fractionated stereotactic radiotherapy. RESULTS: Forty-one patients were
treated: 23 patients with primary ONSM and 18 patients with secondary ONSM. The
median age at diagnosis was 56 years. The median visual follow up was 3.8 years
and the median radiologic follow up was 4.4 years. At diagnosis, 36% had normal
vision (20/20-20/40), 10% had mild impairment (<20/40-20/60), 20% had moderate
visual impairment (<20/60-20/200), 27% had severe impairment (<20/200), and 7%
had no light perception. Common acute side effects were headache (32%) and nausea
(15%); 15% of patients required corticosteroids during stereotactic radiotherapy.
Chronic toxicities included retinopathy (7%), pituitary dysfunction (13%),
chronic ocular pain (5%), and cataracts (2%). Visual acuity was stable in 65%,
improved in 27%, and decreased in 8% of patients. Visual fields were stable in
70%, improved in 21%, and reduced in 9%. Actuarial 5-year local control rates
were 100% for primary ONSM and 88% for secondary ONSM. Actuarial 5-year visual
preservation rates were 100% for primary ONSM and 86% for secondary ONSM.
CONCLUSIONS: Fractionated stereotactic radiotherapy for primary and secondary
ONSM was well tolerated and provides excellent local control and visual
preservation. Longer follow up is required to determine the risk of late ocular
and pituitary sequelae.
PMID- 28422770
TI - Technical Alterations during an Incremental Field Test in Elite Male Tennis
Players.
AB - PURPOSE: We investigated technical and physiological responses along with their
relationships during an incremental field test to exhaustion specific to tennis
(TEST) in elite players. METHODS: Twenty male elite tennis players completed
TEST, which consisted of hitting alternatively forehand and backhand strokes at
increasing ball frequency (ball machine) every minute. Ball accuracy (BA), ball
velocity (BV), and tennis performance (TP) index (TP = BA * BV) were determined
by radar and video analysis for each stroke, in addition to cardiorespiratory
responses and blood lactate concentrations. RESULTS: At low intensities (less
than 80% of maximal oxygen uptake [VO2max]), technical performance was steady.
From 80% to 100% of VO2max, significant and steady decreases in BV (-9.0% and
13.3%; P = 0.02 and P = 0.002), BA (-19.4% and -18.4%; both P < 0.001), and TP (
27.4% and -29.15%; both P = 0.002) occurred for forehands and backhands,
respectively. Changes in TP and blood lactate concentration from 60% to 100% of
VO2max were inversely correlated (r = -0.51, P = 0.008). BV was 5.2% higher (P =
0.042) for forehand versus backhand, and there was no difference between strokes
for both BA (P = 0.930) and TP (P = 0.536). CONCLUSION: Technical alterations
(i.e., decrease in BV, BA, and TP) in elite players undergoing TEST only occurred
at high intensity (>80% of VO2max), presumably because of the use of compensatory
strategies to overcome fatigue. Above this intensity, all technical indices
decreased steadily until exhaustion, independently of the stroke nature.
PMID- 28422771
TI - Slow Intermuscular Oscillations are Associated with Cocontraction Steadiness.
AB - PURPOSE: Voluntary muscle contraction often involves low-frequency correlated
neural oscillations across muscles, which may degrade steady cocontraction
between antagonistic muscles with distinct levels of activation per each muscle
(unbalanced cocontraction). The purposes of the study were 1) to determine
whether there is an association between the low-frequency correlated EMG
oscillations and the performance of steady unbalanced cocontraction across
individuals and 2) to determine whether a bout of out-of-phase cocontraction
practice reduces the in-phase low-frequency correlated neural oscillations and
improves the performance of steady unbalanced cocontraction. METHODS: Healthy
young adults were divided into three intervention groups: cocontraction,
contraction, and control. All participants were tested for unbalanced steady
cocontractions with antagonistic muscles about the elbow joint before and after a
bout of intervention with the visual feedback of surface EMG. During the
intervention period, the cocontraction group practiced an out-of-phase
cocontraction, whereas the contraction group practiced agonist contractions.
RESULTS: Mean squared error and variance of EMG amplitude were positively
correlated with low-frequency EMG coherence <3 Hz across subjects, which became
more prevalent after the intervention period. There was no specific effect of the
cocontraction intervention on these variables. CONCLUSION: These findings suggest
that individuals with less low-frequency correlated neural oscillations tend to
perform steady cocontraction more skillfully, and the low-frequency correlated
oscillations may not be acutely modulated by one bout of out-of-phase
cocontraction practice.
PMID- 28422772
TI - Can Ultrasound Imaging Predict the Success of an Experimental Steatofibrosis
Model?
AB - Our goal was to evaluate the role of ultrasound (US) imaging in an experimental 2
hit steatofibrosis rat model. Nineteen female Sprague-Dawley rats were divided
into 2 groups: control group (n = 6) and high-fat diet carbontetrachloride (HFD
CCl4) group (n = 13) that was fed with HFD for 14 weeks. Ultrasound was performed
to evaluate liver steatosis. The HFD-CCl4 group rats were divided further into 2
subgroups: HFD rats with liver steatosis [US (+) group; n = 6] and without
steatosis [US (-) group; n = 7]. All rats in the subgroups were administered with
CCl4. In both US (+) and US (-) subgroups, steatosis score, fibrosis score,
triglyceride, and hydroxyproline contents were markedly higher compared with the
control group. When compared with the US (-) group, triglyceride and
hydroxyproline contents were significantly higher in the US (+) group, whereas
steatosis and fibrosis scores were not different. Ultrasound imaging may be
useful to assess the success of a 2-hit experimental steatofibrosis model.
PMID- 28422773
TI - Infections in rheumatoid arthritis.
AB - PURPOSE OF REVIEW: The purpose of this review is to provide an update concerning
recent advances in the evidence- based study of serious infections in patients
with rheumatoid arthritis (RA) treated with biological drugs or conventional
disease-modifying antirheumatic drugs (DMARDs), concentrating on studies
published in the last 18 months. RECENT FINDINGS: New studies have further
strengthened existing evidence relating the use of biological drugs to serious
infections. The risk does not seem to be any different with short-term or long
term use. There is still a lack of conclusive studies identifying biomarkers, but
it is plausible that the drugs have direct effects on cytokines and cell activity
and then serious infections. SUMMARY: The frequent infections of patients with RA
may be due to the disease itself (altered immunological function, disability,
immobility, joint surgery), extra-articular manifestations or DMARDs,
immunosuppressants and steroids. The use of biological drugs lead to the
development of serious infections including tuberculosis. Patients should be
informed of their increased risk, and physicians need to be aware of these
complications and how to treat them.
PMID- 28422774
TI - Squamous Cellular Carcinoma Antigen Serum Determination as a Biomarker of Barrett
Esophagus and Esophageal Cancer: A Phase III Study.
AB - GOAL: To evaluate the potential role of the determination of the immunocomplexed
form of squamous cell carcinoma antigen [SCCA-immunoglobulin (Ig)M] for the
screening of Barrett esophagus (BE) and esophageal adenocarcinoma (EAC).
BACKGROUND: The cost-effectiveness of surveillance in BE is still debated and the
use of biomarkers in screening and surveillance still not recommended. No
information is available regarding SCCA-IgM determination in BE. STUDY: SCCA-IgM
levels were determined (enzyme-linked immunosorbent assay) in 231 patients
prospectively recruited, 71 with BE, 53 with EAC, and 107 controls, including 42
blood donors and 65 patients with gastroesophageal reflux. SCCA-IgM cutoffs
between BE/EAC and controls and for BE "at risk" versus short nondysplastic BE
were calculated by receiver operating characteristic curves. Immunostaining for
SCCA-IgM was obtained in a subgroup of patients. RESULTS: Median SCCA-IgM values
were significantly higher in BE and EAC than in controls (P=0.0001). Patients
with SCCA-IgM levels above the cutoff had a 33 times higher relative risk of
harboring BE or EAC (P=0.0001). Patients "at risk," with long or dysplastic BE
had SCCA-IgM levels significantly higher than those with short nondysplastic BE
(P=0.035) and patients with SCCA-IgM above the cutoff had a 8 times higher
relative risk of having BE "at risk." SCCA was expressed in Barrett mucosa but
not in cardiac metaplasia. CONCLUSIONS: Serum SCCA-IgM determination allows the
identification of patients at risk for BE/EAC and the stratification of BE
patients in subgroups with different cancer risk. Because of the still limited
number of controls, large, prospective studies are required to confirm this
evidence.
PMID- 28422776
TI - Lower Cranial Nerves Paralysis Following Prone-Position Mechanical Ventilation.
AB - OBJECTIVE: To communicate a complication of prone-position ventilation. DATA
SOURCES: Case history. STUDY SELECTION: Case report. DATA EXTRACTION AND DATA
SYNTHESIS: Clinical information from medical record. CONCLUSIONS: This is a very
infrequent cause of dysphagia following prone-position ventilation.
PMID- 28422775
TI - A Contemporary Assessment of Acute Mechanical Ventilation in Beijing:
Description, Costs, and Outcomes.
AB - OBJECTIVE: To evaluate the contemporary practice, outcomes, and costs related to
mechanical ventilation among ICUs in China. DESIGN: A prospective observational
cohort study. SETTING: Fourteen ICUs among 13 hospitals in Beijing, China.
PATIENTS: Seven hundred ninety-three patients who received at least 24 hours of
mechanical ventilation within the first 48 hours of ICU stay. INTERVENTION: None.
MEASUREMENTS AND RESULTS: The mean age was 64 years. Sixty-three percent were
male. New acute respiratory failure accounted for 85.5% of mechanical ventilation
cases. Only 4.7% of the patients received mechanical ventilation for acute
exacerbation of chronic obstructive pulmonary disease. The most widely used
ventilation mode was the combination of synchronized intermittent mandatory
ventilation and pressure support (43.6%). Use of lung-protective ventilation is
widespread with tidal volumes of 7.1 mL/kg (2.1 mL/kg). The ICU/hospital
mortality was 27.6%/29.3%, respectively (8.5%/9.7% for surgical patients and
41.3%/43.2% for medical patients, respectively). The mean level of ICU/hospital
cost per patient was $15,271 (18,940)/$22,946 (25,575), respectively. The mean
daily ICU cost per patient was $1,212. CONCLUSION: For the first time, we
obtained a preliminary epidemiology data of mechanical ventilation in Beijing,
China, through the study. Compared with the other nations, our patients are
older, predominantly male, and treated according to prevailing international
guidelines yet at a relatively high cost and high mortality. The expanding
elderly population predicts increase demand for mechanical ventilation that must
be met by continuous improvement in quality and efficiency of critical care
services.
PMID- 28422777
TI - Population-Based Epidemiology of Sepsis in a Subdistrict of Beijing.
AB - OBJECTIVE: Information about the epidemiology of sepsis in community residents in
China remains scarce and incomplete. The purpose of this study was to describe
the occurrence rate and outcome of sepsis in Yuetan Subdistrict of Beijing and to
estimate the occurrence rate of sepsis in China. DESIGN: Retrospective cohort
study. SETTING: All public hospitals serving residents in Yuetan Subdistrict,
Beijing. PATIENTS: All patients (n = 1,716) meeting criteria for sepsis based on
American College of Chest Physicians/Society of Critical Care Medicine consensus
definition. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We screened all
adult residents in Yuetan Subdistrict who were hospitalized from July 1, 2012, to
June 30, 2014, and reviewed medical records. Patients with sepsis were included
in the analysis. We enrolled 1,716 patients with sepsis out of 21,191
hospitalized adults screened, among whom severe sepsis developed in 256 patients,
and septic shock developed in 233 patients. The crude annual occurrence rates of
sepsis, severe sepsis, and septic shock in Yuetan Subdistrict were 667, 103, and
91 cases per 100,000 population, corresponding to standardized occurrence rates
of 461, 68, and 52 cases per 100,000 population per year, respectively. Both
occurrence rate and mortality increased significantly with age, although males
had higher age-adjusted occurrence rate and mortality. The occurrence rate of
sepsis also exhibited seasonal variation, peaking in winter season. The overall
hospital mortality rate of sepsis was 20.6%, yielding a standardized mortality
rate of 79 cases per 100,000 population per year. CONCLUSIONS: Sepsis is a common
and frequently fatal syndrome in Yuetan Subdistrict, Beijing. The occurrence rate
and mortality of sepsis are significantly higher in males and elderly people.
PMID- 28422778
TI - Ultrasound as a Screening Tool for Central Venous Catheter Positioning and
Exclusion of Pneumothorax.
AB - OBJECTIVES: Although real-time ultrasound guidance during central venous catheter
insertion has become a standard of care, postinsertion chest radiograph remains
the gold standard to confirm central venous catheter tip position and rule out
associated lung complications like pneumothorax. We hypothesize that a
combination of transthoracic echocardiography and lung ultrasound is noninferior
to chest radiograph when used to accurately assess central venous catheter
positioning and screen for pneumothorax. SETTING: All operating rooms and
surgical and trauma ICUs at the institution. DESIGN: Single-center, prospective
noninferiority study. PATIENTS: Patients receiving ultrasound-guided subclavian
or internal jugular central venous catheters. INTERVENTIONS: During ultrasound
guided central venous catheter placement, correct positioning of central venous
catheter was accomplished by real-time visualization of the guide wire and
positive right atrial swirl sign using the subcostal four-chamber view. After
insertion, pneumothorax was ruled out by the presence of lung sliding and
seashore sign on M-mode. MEASUREMENTS AND MAIN RESULTS: Data analysis was done
for 137 patients. Chest radiograph ruled out pneumothorax in 137 of 137 patients
(100%). Lung ultrasound was performed in 123 of 137 patients and successfully
screened for pneumothorax in 123 of 123 (100%). Chest radiograph approximated
accurate catheter tip position in 136 of 137 patients (99.3%). Adequate subcostal
four-chamber views could not be obtained in 13 patients. Accurate positioning of
central venous catheter with ultrasound was then confirmed in 121 of 124 patients
(97.6%) as described previously. CONCLUSIONS: Transthoracic echocardiography and
lung ultrasound are noninferior to chest x-ray for screening of pneumothorax and
accurate central venous catheter positioning. Thus, the point of care use of
ultrasound can reduce central venous catheter insertion to use time, exposure to
radiation, and improve patient safety.
PMID- 28422779
TI - The Utility of High-Fidelity Simulation for Training Critical Care Fellows in the
Management of Extracorporeal Membrane Oxygenation Emergencies: A Randomized
Controlled Trial.
AB - OBJECTIVE: Although extracorporeal membrane oxygenation volume has increased,
proficiency in the technology requires extensive training. We compared
traditional water-drill-based extracorporeal membrane oxygenation training with
simulation-based extracorporeal membrane oxygenation training with the hypothesis
that simulation-based training is superior. DESIGN: Randomized controlled trial.
SETTING: Academic medical center. SUBJECTS: Pulmonary/critical care fellows.
INTERVENTIONS: Participants had a preintervention simulated extracorporeal
membrane oxygenation emergency (Sim1-recirculation) then randomized into
simulation and traditional groups. Each group participated in three teaching
scenarios, via high-fidelity simulation or via water-drills. After 6 weeks and
after 1 year, participants returned for two simulated extracorporeal membrane
oxygenation emergencies (Sim2-pump failure and Sim3-access insufficiency). Sim2
was a case encountered during teaching, whereas Sim3 was novel. A critical
action, necessary for resolution of each scenario, was preidentified for timing.
MEASUREMENTS AND MAIN RESULTS: Primary outcome was time required to perform
critical actions. Twenty-one fellows participated in the study (simulation, 10;
traditional, 11). Groups had similar scenario scores (p = 0.4) and times to
critical action (p = 0.8) on Sim1. At 6 weeks, both groups had similar scenario
scores on Sim2 (p = 0.5), but the simulation group scored higher on Sim3 (p =
0.03). Times to critical actions were shorter in the simulation group during Sim2
(127 vs 174 s, p = 0.004) and Sim3 (159 vs 300 s; p = 0.04). These findings
persisted at 1 year. CONCLUSIONS: In novice critical care fellows, simulation
based extracorporeal membrane oxygenation training is superior to traditional
training. Benefits transfer to novel scenarios and are maintained over the long
term. Further studies evaluating the utility of simulation in other learner
groups and for maintenance of proficiency are required.
PMID- 28422780
TI - Understanding the Gut Microbiota in Inflammatory and Functional Gastrointestinal
Diseases.
AB - OBJECTIVE: During the last decade, experimental and observational studies have
shown that patients with inflammatory bowel disease (IBD) and irritable bowel
syndrome (IBS) may have an altered intestinal microbial composition compared with
healthy individuals. However, no uniform microbial signature has as yet been
detected for either IBD or IBS. This review summarizes the current knowledge of
microbial dysbiosis and its potential relationship to the pathophysiology in IBD
and IBS. METHODS: A selective review was conducted to summarize the current
knowledge of gut microbiota in the pathophysiology of IBD and IBS. RESULTS:
Experimental and observational studies provide good evidence for intestinal
microbial dysbiosis in subgroups of IBD and IBS. Still, no uniform disease
pattern has been detected. This is most likely due to the heterogeneous nature of
IBD and IBS, in combination with the effects of intrinsic and extrinsic factors.
Such intrinsic factors include genetics, the gastrointestinal environment, and
the host immune system, whereas extrinsic factors include early life diet,
breastfeeding, and method of infant delivery. CONCLUSIONS: Recent and ongoing
work to define microbial dysbiosis in IBD and IBS shows promise, but future well
designed studies with well-characterized study individuals are needed. It is
likely that the microbial dysbiosis in IBD and IBS is dependent on the natural
disease course of IBD and symptom pattern in IBS. Therefore, assessment of the
entire microbiota along the gastrointestinal tract, in relationship to
confounding factors, symptom fluctuations, and other pathophysiological factors,
is needed for further understanding of the etiology of these common diseases.
PMID- 28422782
TI - Editorial introduction.
PMID- 28422783
TI - Lessons learned from humoral responses of HIV patients.
AB - PURPOSE OF REVIEW: Since 2009 many broadly neutralizing antibodies against HIV
have been identified, yet there is still no vaccine capable of inducing such
antibodies in humans. This review considers the early observations of HIV sera
neutralization in light of more recent studies and highlights areas for future
research. RECENT FINDINGS: Large clinical cohort studies using standardized
neutralization assays and pseudoviruses derived from primary isolates have shown
that 10-30% of HIV infections result in some level of serum neutralization
breadth. However, less than 10% of individuals develop a greater breadth of
neutralization and are termed elite neutralizers. SUMMARY: During HIV infection,
many individuals develop strain-specific neutralization against their viral
quasispecies, and similar immunogen-matched activity can now be induced in animal
models. However, only in a minority of infections do broadly neutralizing
antibodies develop. Therefore, understanding how the viral diversity, host immune
environment, and antibody repertoires intersect to support the generation of
neutralization breadth in elite neutralizers could provide guidelines as to how
to improve immunization responses.
PMID- 28422784
TI - B-cell abnormalities and impact on antibody response in HIV infection.
AB - PURPOSE OF REVIEW: The purpose of the present review is to provide an update on
the current development in the field of broadly neutralizing antibodies (bNabs)
and their potential use in the prevention and therapeutic settings, and an
evaluation of the B-cell abnormalities that may impair antibody responses in HIV
infection. RECENT FINDINGS: Major advances have been achieved in the
characterization of bNabs directed against different vulnerable regions of HIV
Envelope (Env). Recent observations have clearly demonstrated the ability of
bNabs to prevent HIV infection in the nonhuman primate model of HIV infection and
to suppress viremia in individuals with chronic HIV infection in the absence of
antiretroviral therapy. Furthermore, substantial advances have also been obtained
in the development of HIV Env proteins and immunization strategies inducing bNabs
in small animal models. Several studies have also shed light on the B-cell
abnormalities associated with the viremic phase of HIV infection that cause
impaired B-cell maturation and antibody responses. Of note, preliminary
observations have provided evidence for a correlation between the expansion of a
specific population of B cells, for example, germinal center B cells, the
expansion of T follicular helper cells (Tfh), and the generation of neutralizing
antibodies. SUMMARY: The recent observations on the antiviral effects of bNabs in
vivo indicate that bNabs may play a central role in both the prevention and the
therapeutic settings. The identification of the role of germinal center B cells
and Tfh cells as critical components of the immune response leading to the
generation of neutralizing antibodies, will allow the development of specific
immunization strategies for the stimulation of germinal center B cells and Tfh
cells. A lot of work still remains to be done for the delineation of B-cell and
Tfh cell biology from human lymphoid tissues and in the development of HIV Env
proteins and immunization strategies leading to the generation of bNabs.
PMID- 28422785
TI - Role of nonneutralizing antibodies in vaccines and/or HIV infected individuals.
AB - PURPOSE OF REVIEW: Increased body of evidence gathered over time indicate that
antibodies are capable of many inhibitory mechanisms, virus neutralization being
just one of them. Nonneutralizing antibodyactivities interfering with HIV
replication can also lead to a decrease in viral load and even in-vivo
protection. RECENT FINDINGS: It was previously believed that neutralizing
antibodies can achieve sterilizing protection mainly by using their
neutralization capacities against the infecting virus directly at the portal of
virus entry. Recent findings show that protection can be obtained by neutralizing
antibodiesat distal sites of virus challenge. In this case, foci of virus
infection that escaped from initial inhibition of virus are eliminated presumably
by additional nonneutralizing antibody activities. These data inexorably
strengthen the diverse functions of antibodies and broaden their role as
antiviral mediator. SUMMARY: The review summarizes the current knowledge and the
difficulties to encompass the numerous functions of antibodies. A complete
understanding of the various facets of antibody functions is required to
efficiently induce them via next-generation vaccine design.
PMID- 28422786
TI - Antibody-mediated immune exclusion of HIV.
AB - PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans
occur through mucosal contact, the induction of mucosal anti-HIV immune responses
has remained understudied. Here we summarize data demonstrating the powerful
protection that is achievable at mucosal frontlines through virus-specific
mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization
with different monoclonal antibody subclasses but identical epitope specificity
(the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1
(dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus
(SHIV) acquisition in rhesus macaques at a higher rate than dIgA2. Both dIgAs
neutralized the challenge SHIV equally well. Protection was linked to better
virion capture and inhibition of cell-free virus transcytosis by dIgA1.
Synergistic interactions at the mucosal level between the IgG1 and dIgA2 versions
of this monoclonal antibody yielded complete protection. Active vaccine
strategies designed to induce mucosal IgA and systemic/mucosal IgG have given
promising data. SUMMARY: This review seeks to highlight the importance of mucosal
IgAs in preventing virus acquisition. Passive immunization gave proof-of-concept
for immune exclusion by mucosally administered monoclonal dIgAs. Unanswered
questions remain regarding the interplay between mucosal IgA and other host
immune defenses, including their induction with active immunization.
PMID- 28422787
TI - How HIV-1 entry mechanism and broadly neutralizing antibodies guide structure
based vaccine design.
AB - PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies
(bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1
entry mechanism is guiding the structure-based design of vaccine immunogens and
immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected
donors has led to an unprecedented understanding of the sites of vulnerability
that these antibodies target on the HIV-1 envelope (Env) as well as of the
immunological pathways that these antibody lineages follow to develop broad and
potent neutralization. Sites of vulnerability, however, reside in the context of
diverse Env conformations required for HIV-1 entry, including a prefusion-closed
state, a single-CD4-bound intermediate, a three-CD4-bound intermediate, a
prehairpin intermediate and postfusion states, and it is not always clear which
structural state optimally presents a particular site of vulnerability in the
vaccine context. Furthermore, detailed knowledge of immunological pathways has
led to debate among vaccine developers as to how much of the natural antibody
developmental pathway immunogens should mimic, ranging from only the recognized
epitope to multiple antigens from the antibody-virus coevolution process.
SUMMARY: A plethora of information on bNAbs is guiding HIV-1-vaccine development.
We highlight consideration of the appropriate structural context from the HIV-1
entry mechanism and extraordinary progress with replicating template B-cell
ontogenies.
PMID- 28422789
TI - Antigp41 membrane proximal external region antibodies and the art of using the
membrane for neutralization.
AB - PURPOSE OF REVIEW: We summarize the latest research on the progress to understand
the neutralizing epitopes present within the membrane proximal external region
(MPER) of the HIV-1 fusion protein subunit gp41. RECENT FINDINGS: The HIV-1
fusion protein subunit gp41 contains a highly conserved sequence that is
essential for membrane fusion and targeted by broadly neutralizing antibodies
such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41
epitope with high affinity, but require additional hydrophobic sequences present
in their heavy chain CDR3 for neutralization. Recent structural studies on mAbs
4E10 and 10E8 provide molecular details for specific interactions with lipids and
implicate part of the transmembrane region as the relevant 10E8 epitope. Although
many different approaches have been applied to engineer gp41 immunogens that can
induce broadly neutralizing antibodies directed toward MPER, only modest success
has yet been reported. SUMMARY: The new structural details on the complex gp41
lipidic epitope will spur new approaches to design gp41-MPER immunogens that
might induce broadly neutralizing antibody responses.
PMID- 28422790
TI - Particle-based delivery of the HIV envelope protein.
AB - PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of
suitable antigens that elicit broadly neutralizing antibody responses targeting
HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle
based carriers allows higher avidity interactions and is therefore expected to
efficiently engage B cells, thus leading to affinity maturation that results in
superior antibody responses characterized by improved breadth, potency, and
durability. This review summarizes current work that is evaluating diverse types
of such particulate carriers for Env delivery. RECENT FINDINGS: Various types of
particle scaffolds are being investigated, encompassing group-specific antigen
derived virus-like particles, bacteria-derived proteins that self-assemble into
symmetrical nanoparticles, as well as liposomes assembled from membrane
components and recombinantly produced Env isoforms. Env-derived antigens from
peptides over selected isolates to improved, stabilized next-generation designer
Envs have been attached to such carriers. Immunological evaluation in animal
models showed that these structures often elicit superior humoral immune
responses. SUMMARY: The findings reviewed here emphasize the potential of
particle-based delivery modalities to elicit better antibody responses. Together
with advances in Env antigen design, these approaches may synergistically act
together on the way to obtain vaccine candidates that potentially induce
protective immune responses against HIV.
PMID- 28422788
TI - Stabilized HIV-1 envelope glycoprotein trimers for vaccine use.
AB - PURPOSE OF REVIEW: To provide an update on the latest developments in the field
of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for
vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env
trimer immunogens has moved the field of antibody-based vaccine design forward
dramatically over the past few years with refinement of various stabilizing
approaches. However, despite this progress, significant challenges remain.
Firstly, although trimers are relatively stable in solution, they nevertheless
sample different conformational states, some of which may be less relevant to
binding and induction of broadly neutralizing antibodies (bNAbs). Secondly, these
trimers expose unwanted immunodominant surfaces that may distract the adaptive
immune response from recognizing more immunorecessive but conserved
neutralization-relevant surfaces on the trimer. The availability of atomic
resolution structural information has allowed guided design of mutations that
have further stabilized trimers and allowed reduced exposure of unwanted
epitopes. Moreover, chemical cross-linking approaches that do not require
structural information have also contributed to trimer stabilization and
selection of particular conformational forms. However, current knowledge suggests
that strategies additional to trimer stabilization will be required to elicit
bNAb, including targeting naive B cell receptors with specific immunogens, and
guiding B cell lineages toward recognizing conserved surfaces on Env with high
affinity. SUMMARY: This review will give a perspective on these challenges, and
summarize current approaches to overcoming them with the aim of developing
immunogens to elicit bNAb responses in humans by active vaccination.
PMID- 28422791
TI - Intrastructural help: improving the HIV-1 envelope antibody response induced by
virus-like particle vaccines.
AB - PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy
of HIV vaccines is increasingly recognized. Although different types of vaccines
were shown to induce antibodies with different Fc-activities, there is no clear
strategy how to raise antibody responses with a desired pattern of Fc-effector
functions. Given the central role of T-helper cells in regulating the germinal
center reaction and the differentiation of B cells in an antigen-specific manner,
the review will discuss whether T-helper cells directed against non-HIV envelope
(Env) antigens could be harnessed to improve the HIV-Env antibody response.
RECENT FINDINGS: Comparing CD4 T-cell responses in HIV-infected individuals with
and without neutralizing antibody breadth suggests that robust Gag-specific CD4 T
cells may provide important T-cell help to Env-specific B cells. In a murine
model, GagPol-specific T-helper cells were shown to provide intrastructural help
for HIV-Env-specific antibody responses after immunization with a virus-like
particle vaccine. GagPol-specific T-helper cells imprinted the IgG subtype ratio
observed for Gag onto the HIV-Env antibody response and modulated the
glycosylation pattern of the HIV Env-specific antibodies. SUMMARY:
Intrastructural help is a promising strategy to improve overall levels and Fc
effector functions of the HIV-Env antibody response.
PMID- 28422792
TI - Progress in HIV-1 antibody research using humanized mice.
AB - PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing
antibodies provide new opportunities to successfully prevent, treat, and
potentially cure HIV-1 infection. To test their activity in vivo, humanized mice
have been shown to be a powerful model and were used to investigate antibody
mediated prevention and therapy approaches. In this review, we will summarize
recent findings in humanized mice that have informed on the potential use of
broadly neutralizing antibodies targeting HIV-1 in humans. RECENT FINDINGS:
Humanized mouse models have been used to demonstrate the antiviral efficacy of
HIV-1 neutralizing antibodies in vivo. It has been shown that a combination of
antibodies can suppress viremia below the limit of detection and targets the HIV
1 reservoir. Moreover, passively administered antibodies and vector-mediated
antibody production protect humanized mice from HIV-1 infection. Finally,
immunization studies in knock-in/transgenic mice carrying human antibody gene
segments have informed on potential vaccination strategies to induce broad and
potent HIV-1 neutralizing antibodies. SUMMARY: Humanized mouse models are of
great value for HIV-1 research. They represent a highly versatile in vivo system
to investigate novel approaches for HIV-1 prevention and therapy and expedite the
critical translation from basic findings to clinical application.
PMID- 28422794
TI - Intrathecal Morphine in Spine Surgery: A Meta-analysis of Randomized Controlled
Trials.
AB - STUDY DESIGN: Meta-analysis of randomized controlled trials (RCTs). OBJECTIVE:
The aim of this study was to evaluate the effectiveness of intrathecal morphine
(ITM) in reducing postoperative pain and opioid analgesic consumption following
spine surgery. SUMMARY OF BACKGROUND DATA: The use of ITM following adult spine
surgery is of particular interest because of the ease of access to the thecal sac
and the potential to provide adequate analgesia at low doses. However, previous
studies of ITM have been limited by small sample sizes and conflicting results.
METHODS: A comprehensive search of PubMed, Web of Science, Clinicaltrials.gov,
and the Cochrane Central Register of Controlled Trials for prospective RCTs was
performed by two independent reviewers. Postoperative opioid consumption, pain
scores, and complications were documented from the identified studies. Standard
mean differences (SMDs) were applied to continuous outcomes and odds ratios were
determined for dichotomous outcomes. RESULTS: Eight RCTs involving 393 subjects
met inclusion criteria and were included in this meta-analysis. Patients
receiving ITM (ITM group) as an adjunct to postoperative opioid analgesic were
compared to patients receiving postoperative opioids only (control group).
Postoperative morphine equivalent consumption was significantly lower during the
first 24 hours postoperative in the ITM group (P < 0.001). Pain scores were
similarly lower in the first 24 hours following spine surgery in those who
received ITM (P < 0.001). In patients administered ITM, a greater percentage
experienced pruritus (P < 0.001). Respiratory depression was solely encountered
in the ITM group (P = 0.25). There were no significant differences between the
ITM and control groups in terms of sedation (P = 0.18), nausea (P = 0.67),
vomiting (P = 0.62), or length of stay (P = 0.13). CONCLUSION: In patients
undergoing spine surgery, use of ITM significantly reduced opioid analgesic
consumption and Visual Analogue Schores pain scores compared to controls within
the first 24 hours postoperatively. High-quality, follow-up RCTs with large
sample sizes are recommended to determine the potential of supplementary ITM in
spine surgery and complete the side effects profile. LEVEL OF EVIDENCE: 1.
PMID- 28422795
TI - Trial Design and Endpoint Evaluation in Clinical Studies Addressing Chronic Back
Pain.
AB - STUDY DESIGN: A review of the literature evaluating clinical trials of chronic
back pain. OBJECTIVE: To assist physicians in assessing the quality of clinical
trial data to make the most informed treatment decisions. SUMMARY OF BACKGROUND
DATA: Chronic pain is a tremendous public health issue, affecting close to 100
million adults in the United States, and costs the American people billions of
dollars. One traditional treatment approach, the long-term use of opiate
medications, has recently come under intense scrutiny for problems with
complications, diversion, abuse, addiction, and lack of efficacy. In addition,
the Centers for Disease Control and Prevention has recognized that
overprescribing opiates has enabled an overdose crisis, and written guidelines
that are intended to limit their use. It is for this reason that physicians must
have a comprehensive understanding of the range of drug-free alternative
therapies available and have the tools needed to rigorously evaluate the chronic
pain literature so they can make appropriate treatment decisions. METHODS: An
evaluation of how clinical trials are designed and ranked, outcome measures, and
costs for a variety of therapies is necessary to determine which treatment option
is the most efficacious for an individual patient. RESULTS: Clinical trial data
demonstrate that spinal cord stimulation (SCS) is a safe and effective treatment
option for many types of chronic pain, including back pain. The last 10 years has
brought tremendous advances in the field of neuromodulation. Today, several
treatment modalities exist for SCS requiring the physician to be able to
critically evaluate and interpret the literature and determine which modality has
the strongest evidence. When evaluating clinical trial data of patients with
chronic back pain, emphasis must be placed on well designed, randomized
controlled trials with long-term follow-up producing level I evidence. These data
are obtained in a rigorous manner and are likely to have less bias when compared
with lower level studies. CONCLUSION: The level I studies performed to date have
provided evidence that treatment with SCS results in sustainable pain reduction
and improvements in scores measuring quality of life and patient functioning in
those patients with chronic intractable back pain. LEVEL OF EVIDENCE: 5.
PMID- 28422793
TI - Engineering antibody-like inhibitors to prevent and treat HIV-1 infection.
AB - PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that
can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an
emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than
any single antibody characterized to date. We also discuss the use of recombinant
adeno-associated virus (rAAV) vectors as a platform for long-term expression of
these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be
targeted by broadly neutralizing antibodies (bNAbs). Recent studies combine the
variable regions or Fabs from different bNAbs, often with the receptor-mimetic
components, to create broad, potent, and hard-to-escape inhibitors. rAAV vectors
can express these inhibitors for years in vivo, highlighting their ability to
prevent or treat HIV-1 infection. SUMMARY: By targeting multiple epitopes on Env,
bispecific and antibody-like inhibitors can be broader and more potent than
bNAbs. These inhibitors can provide long-term protection from, and perhaps
suppression of, HIV-1 if they are administered by a delivery platform, like rAAV
vectors, but only after rAAV limitations are addressed.
PMID- 28422796
TI - Waterless Hand Rub Versus Traditional Hand Scrub Methods for Preventing the
Surgical Site Infection in Orthopedic Surgery.
AB - : MINI: Fourteen hundred consecutive patients were investigated for evaluating
the utility of waterless hand rub before orthopaedic surgery. The risk in the
surgical site infection incidence was the same, but costs of liquids used for
hand hygiene were cheaper and the hand hygiene time was shorter for waterless
protocol, compared with traditional hand scrub. STUDY DESIGN: A retrospective
cohort study with prospectively collected data. OBJECTIVE: The aim of this study
was to compare SSI incidences, the cost of hand hygiene agents, and hand hygiene
time between the traditional hand scrub and the waterless hand rub protocols
before orthopedic surgery. SUMMARY OF BACKGROUND DATA: Surgical site infections
(SSI) prolong hospitalization and are a leading nosocomial cause of morbidity and
a source of excess cost. Recently, a waterless hand rub protocol comprising
alcohol based chlorhexidine gluconate for use before surgery was developed, but
no studies have yet examined its utility in orthopedic surgery. METHODS: Fourteen
hundred consecutive patients who underwent orthopedic surgery (spine, joint
replacement, hand, and trauma surgeries) in our hospital since April 1, 2012 were
included. A total of 712 cases underwent following traditional hand scrub between
April 1, 2012 and April 30, 2013 and 688 cases underwent following waterless hand
rub between June 1, 2013 and April 30, 2014. We compared SSI incidences within
all and each subcategory between two hand hygiene protocols. All patients were
screened for SSI within 1 year after surgery. We compared the cost of hand
hygiene agents and hand hygiene time between two groups. RESULTS: The SSI
incidences were 1.3% (9 of 712) following the traditional protocol (2 deep and 7
superficial infections) and 1.1% (8 of 688) following the waterless protocol (all
superficial infections). There were no significant differences between the two
groups. The costs of liquids used for one hand hygiene were about $2 for
traditional hand scrub and less than $1 for waterless hand rub. The mean hand
hygiene time was 264 seconds with the traditional protocol and 160 seconds with
the waterless protocol. CONCLUSION: Waterless hand rub with an alcohol based
chlorhexidine gluconate solution can be a safe, quick, and cost-effective
alternative to traditional hand scrub. LEVEL OF EVIDENCE: 3.
PMID- 28422798
TI - Anterior Versus Posterior Thoracic Discectomy: A Systematic Review.
AB - STUDY DESIGN: Systematic literature review. OBJECTIVE: The aim of this study was
to systematically review the current evidence in the literature on thoracic
discectomies, to compare the clinical outcomes, and to determine whether there is
evidence to support the use of either the anterior or posterior approach. SUMMARY
OF BACKGROUND DATA: Thoracic disc herniations (TDHs) often present with
myelopathy, radiculopathy, or a combination of both. The posterior approach for
thoracic discectomy has been associated with a lower complication rate, but no
systematic review exists comparing the clinical outcomes. METHODS: MEDLINE,
EMBASE, and The Cochrane Library databases were searched in accordance with the
PRISMA guidelines for studies performing an anterior or posterior thoracic
discectomy. The methodological quality was assessed using the Methodological
Index for Non-Randomized Studies checklist. The reported clinical outcomes were
evaluated using risk ratio, with a P < 0.05 being considered statistically
significant. RESULTS: Thirty-seven clinical studies with 1156 patients with 1300
TDHs were included in this review. There was no statistically significant
difference in the total neurological improvement or neurological worsening using
either an anterior approach or a posterior approach (P = 0.02812 and P = 0.5232,
respectively). However, there was a statistically significant higher rate of
total complications in the anterior approach (P = 0.0024). CONCLUSION: The
anterior approach and posterior approach have been shown to be very similar in
terms of neurological outcomes. Although the posterior approach was shown to have
a lower rate of total complications, this was largely because of a decrease in
minor respiratory complications seen in the anterior approach. The optimal
approach may therefore be based on surgeon preference as well as patient factors,
specifically cardiorespiratory with American Society of Anaesthesiologists
grading. LEVEL OF EVIDENCE: 4.
PMID- 28422799
TI - Publication Rates of Abstracts Accepted to the 2010-2012 Annual Meetings of the
North American Spine Society.
AB - : MINI: The publication rate of conference abstract presentations as full-length
manuscripts is a potential measure of meeting quality. 43.8% of abstracts
presented at the 2010-2012 North American Spine Society annual meetings were
published as full-length manuscripts within 3 years. Podium presentations and
"Best" or "Outstanding" paper presentations were more likely to be published.
STUDY DESIGN: Retrospective review of conference abstracts. OBJECTIVE: The aim of
this study was to determine the publication rate of podium and poster
presentations at the 2010-2012 North American Spine Society (NASS) annual
meetings. SUMMARY OF BACKGROUND DATA: Presentations at medical conferences are
utilized to disseminate new clinical information. The orthopedic literature
estimates the rate of publication for abstracts presented at major meetings to be
between 34.0% and 67.1%. However, few studies have analyzed the publication rate
of accepted abstracts to the NASS annual meetings. METHODS: All abstracts
presented at the 2010-2012 NASS annual meetings were reviewed. PubMed and Google
Scholar databases were searched to determine whether each abstract was published
as a full-length manuscript before or up to 3 years after its NASS meeting
presentation. Statistical analyses included descriptive statistics, Poisson
regression with robust error variance, and linear regression. RESULTS: A total of
1045 abstracts were accepted to the 2010-2012 NASS annual meetings. 43.8% were
published before or up to 3 years after their NASS presentation. Podium
presentations were more likely to be published than poster presentations (47.1%
vs. 37.7%, P = 0.005). Abstracts with "Best" or "Outstanding" designations were
also more likely to be published than abstracts without those designations (54.4%
vs. 45.0%, P = 0.034). Presentations designated as "Best" or "Outstanding"
articles had shorter time to publication than presentations without those
designations (369 vs. 486 days, P = 0.002). CONCLUSION: This study suggests that
only 43.8% of abstracts accepted to NASS are published as full-length
manuscripts. As such, practitioners should use caution when altering clinical
practice based solely on conference presentations. Additionally, podium
presentations are more likely to be published than poster presentations. This
trend may be reflective of the higher quality of abstracts accepted as podiums,
or may be associated with a larger number of lower-quality abstracts being
accepted because of the use of the e-poster format. LEVEL OF EVIDENCE: 4.
PMID- 28422800
TI - Evaluation of Water Content in Lumbar Intervertebral Discs and Facet Joints
Before and After Physiological Loading Using T2 Mapping MRI.
AB - STUDY DESIGN: T2 mapping was used to quantify the water content of lumbar spine
intervertebral discs (IVDs) and facet joints before and after physiological
loading. OBJECTIVE: The aim of this study was to clarify the interaction between
lumbar spine IVD and facet joints as load-bearing structures by measuring the
water content of their matrix after physiological loading using T2 mapping
magnetic resonance imaging (MRI). SUMMARY OF BACKGROUND DATA: To date, few
reports have functionally evaluated lumbar spine IVD and facet joints, and their
interaction in vivo. T2 mapping may help detect changes in the water content of
IVD and articular cartilage of facet joints before and after physiological
loading, thereby enabling the evaluation of changes in interacted water retention
between IVD and facet joints. METHODS: Twenty asymptomatic volunteers (10 female
and 10 male volunteers; mean age, 19.3 years; age range, 19-20 years) underwent
MRI before and after physiological loading such as lumbar flexion, extension, and
rotation. Each IVD from L1/2 to L5/S1 was sliced at center of the disc space, and
the T2 value was measured at the nucleus pulposus (NP), anterior annulus fibrosus
(AF), posterior AF, and bilateral facet joints. RESULTS: In the NP, T2 values
significantly decreased after exercise at every lumbar spinal level. In the
anterior AF, there were no significant differences in T2 values at any level. In
the posterior AF, T2 values significantly increased only at L4/5. In the
bilateral facet joints, T2 values significantly decreased after exercise at every
level. CONCLUSION: There was a significant decrease in the water content of facet
joints and the NP at every lumbar spinal level after dynamic loading by physical
lumbar exercise. These changes appear to play an important and interactional role
in the maintenance of the interstitial matrix in the IVD NP and cartilage in the
facet joint. LEVEL OF EVIDENCE: 3.
PMID- 28422801
TI - Interrater and Test-Retest Reliability of the Beery Visual-Motor Integration in
Schoolchildren.
AB - PURPOSE: To assess interrater and test-retest reliability of the 6th Edition
Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) and test
retest reliability of the VMI Visual Perception Supplemental Test (VMIp) in
school-age children. METHODS: Subjects were 163 Native American third- to eighth
grade students with no significant refractive error (astigmatism <1.00 D, myopia
<0.75 D, hyperopia <2.50 D, anisometropia <1.50 D) or ocular abnormalities. The
VMI and VMIp were administered twice, on separate days. All VMI tests were scored
by two trained scorers, and a subset of 50 tests was also scored by an
experienced scorer. Scorers strictly applied objective scoring criteria. Analyses
included interrater and test-retest assessments of bias, 95% limits of agreement,
and intraclass correlation analysis. RESULTS: Trained scorers had no significant
scoring bias compared with the experienced scorer. One of the two trained scorers
tended to provide higher scores than the other (mean difference in standardized
scores = 1.54). Interrater correlations were strong (0.75 to 0.88). VMI and VMIp
test-retest comparisons indicated no significant bias (subjects did not tend to
score better on retest). Test-retest correlations were moderate (0.54 to 0.58).
The 95% limits of agreement for the VMI were -24.14 to 24.67 (scorer 1) and
26.06 to 26.58 (scorer 2), and the 95% limits of agreement for the VMIp were
27.11 to 27.34. CONCLUSIONS: The 95% limit of agreement for test-retest
differences will be useful for determining if the VMI and VMIp have sufficient
sensitivity for detecting change with treatment in both clinical and research
settings. Further research on test-retest reliability reporting 95% limits of
agreement for children across different age ranges is recommended, particularly
if the test is to be used to detect changes due to intervention or treatment.
PMID- 28422802
TI - Validity and Repeatability of a Novel Dynamic Visual Acuity System.
AB - PURPOSE: In many sports, athletes rely on visual information from the environment
to perform. Some literature suggests athletes have superior visual abilities to
non-athletes, particularly on tasks representative of the visual demands of their
sport, such as dynamic acuity, eye movement accuracy and speed, and peripheral
vision. Other literature suggests there is no difference between athletes and non
athletes, at least when standard clinical assessments are employed. A limitation
of the literature is that almost none of the research has been conducted with
standardized, validated tools. This is partly caused by a lack of readily
available tools to measure tasks representative of the visual demands of sport,
and available tests have typically not been validated against current clinical
standards. The purpose of this study is to examine the validity and repeatability
of a novel visual acuity system (moV&; V&MP Vision Suite) recently developed in
the Vision & Motor Performance Lab (V&MP). moV& permits the measurement of many
visual function parameters including dynamic visual acuity with predictable,
random, and jittering target motion. METHODS: Twenty-five participants attended
two study visits, separated by a minimum of 2 weeks. At each visit, static and
dynamic visual acuity was measured using Snellen, ETDRS, and moV& charts. Static
visual acuities were compared to determine the validity of moV&, and both static
and dynamic visual acuities were compared between visits to determine the test
retest repeatability. RESULTS: moV& static visual acuities are clinically similar
to visual acuities measured with the ETDRS chart (moV&, -0.09 +/- 0.13; ETDRS,
0.03 +/- 0.11, concordance correlation coefficient 0.726). Additionally, all
static, dynamic, and jitter visual acuities demonstrate good test-retest
repeatability (Lin's concordance correlation coefficient range 0.451-0.953).
CONCLUSIONS: moV& provides good clinical measures of static visual acuity that
are comparable to both Snellen and ETDRS measures. Dynamic visual acuity measures
demonstrate good test-retest repeatability.
PMID- 28422803
TI - Marijuana Use and Self-reported Quality of Eyesight.
AB - PURPOSE: There is increasing use of marijuana among young adults and more states
in the United States are legalizing medical marijuana use. A number of studies
have revealed both the beneficial and harmful effects of marijuana to the human
system. Despite some beneficial effects, studies have shown marijuana to have a
lot of deleterious effects on the visual system, which subsequently reduces the
quality of eyesight. The aim of this study was to investigate if heavy marijuana
smoking is associated with a poor quality of eyesight compared with light/no use
of marijuana. METHODS: The National Longitudinal Survey of Youths (NLSY79), a
nationally representative sample of 12,686 young men and women surveyed in 1979
to 2010 was used for this study. The quality of eyesight of 1304 heavy marijuana
users was compared with 1304 respondents with light or no marijuana use. The t
test, multivariate and weighted logistic regression were used in the data
analysis. RESULTS: There was no statistically significant difference in the self
reported quality of eyesight among heavy marijuana smokers compared with youths
who never used marijuana or are light marijuana users. Among heavy marijuana
smokers, males and high school graduates have decreased odds of reporting a poor
quality of eyesight, whereas blacks have increased odds of reporting a poor
quality of eyesight. CONCLUSIONS: The self-reported quality of eyesight among
marijuana users can aid clinicians and other health practitioners facilitate the
development of sex-, racial/ethnic-, and educational level-informed prevention
and early intervention programs and also help characterize public opinions
regarding cannabis, which are particularly relevant given the ongoing debate
concerning the medicalization and legalization of cannabis in the United States.
PMID- 28422804
TI - A Review of Ocular Graft-Versus-Host Disease.
AB - : Graft-versus-host disease (GVHD) is a major complication that occurs following
allogeneic hematopoietic stem cell transplantation, which is a potential curative
therapy used in a variety of malignant or benign hematological diseases. Graft
versus-host disease primarily occurs in many organs, but most notably in the
skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal
system. Ocular manifestations of GVHD may precede other systemic GVHD findings,
and it may be a poor prognosis for mortality. While all parts of the eye may be
affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or
keratoconjunctivitis sicca is the most common presenting manifestation of chronic
ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which
involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to
tear film deficiency and instability. Depending on the severity of ocular
involvement and response to treatment, ocular GVHD may cause decreased quality of
life. Management of GVHD begins with prevention by understanding risk factors and
by implementing prophylactic treatment after allogeneic hematopoietic stem cell
transplantation. A multidisciplinary approach to the prevention and treatment of
GVHD is important, and there are currently no preventive therapies available for
ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular
surface lubrication and support, tear film stabilization, inflammation reduction,
and surgical intervention. The goal of this review is to define ocular GVHD and
its categorical manifestations, as well as to describe the importance of
comprehensive assessment, diagnosis, and ophthalmologic treatment and management
of ocular GVHD with a multidisciplinary approach.
PMID- 28422805
TI - A Randomized Pilot Study Comparing Ketamine and Methohexital Anesthesia for
Electroconvulsive Therapy in Patients With Depression.
AB - OBJECTIVE: This randomized controlled pilot study examines the differences in
response to electroconvulsive therapy (ECT) as defined by an improvement of
depressive symptoms between ketamine and methohexital as the primary anesthetic
agent. Adverse effects and cognitive tolerability were also examined. METHODS:
Subjects undergoing ECT for unipolar or bipolar depression were randomized to
receive ketamine or methohexital as the anesthetic agent. Primary outcome measure
includes the Hamilton rating scale for depression (17-item). Secondary outcome
measures included the mini-mental status examination and Beck depression
inventory. All ratings were conducted masked to anesthetic agent. Because of
multiple outcome measures obtained over time, mixed models were used to account
for the correlations among the measurements within the subjects. Because outcomes
were either normally distributed or approximately normally distributed, general
linear mixed models were fit with a random intercept specified. RESULTS: A total
of 21 subjects were enrolled, and 16 were randomized (methohexital, n = 8;
ketamine, n = 8). The 2 treatment groups did not differ statistically in any
demographic characteristic. No statistical difference was found between the
ketamine and methohexital groups for an improvement in depressive symptoms (P =
0.6); however, subjects in both groups showed significant improvement in
depression over time (ketamine, P < 0.0001; methohexital, P < 0.0001). Mini
mental status examination results did not differ between groups, and fatigue was
reported more in subjects receiving ketamine (P = 0.03). CONCLUSIONS: The results
of this pilot study are inconclusive because they lack power to support an
advantage of ketamine anesthesia compared with methohexital in ameliorating
depressive symptoms for electroconvulsive therapy.
PMID- 28422806
TI - Improvement of Image Quality in Unenhanced Dual-Layer CT of the Head Using
Virtual Monoenergetic Images Compared With Polyenergetic Single-Energy CT.
AB - OBJECTIVES: The aims of this study were to compare virtual monoenergetic images
and polyenergetic images reconstructed from unenhanced dual-layer detector
computed tomography (DLCT) of the head and to determine kiloelectron volt levels
that optimize image quality, particularly the gray-white matter contrast, and
reduce beam hardening artifacts caused by the skull. MATERIALS AND METHODS:
Institutional review board approval was obtained. Forty patients that received
DLCT were included in this retrospective study; of these patients, 22 were women
and 18 were men. The average age was 61.5 +/- 14.3 years. Virtual monoenergetic
images were reconstructed from spectral base images at 40 keV to 120 keV. To
calculate signal-to-noise ratio and contrast-to-noise ratio, attenuation and
standard deviation of supratentorial gray and white matter were measured in
virtual monoenergetic and polyenergetic images. Beam hardening artifacts were
detected close to the calvarium and in the posterior fossa. Two radiologists
rated the assessment of gray-white matter differentiation and of the subcalvarial
space, as well as the artifacts caused by the skull and image noise. Student t
test and Wilcoxon test were used to determine significance. RESULTS: Compared
with polyenergetic images, superior signal-to-noise ratio and superior contrast
to-noise ratio of gray and white matter were observed in virtual monoenergetic
images at low kiloelectron volt levels (P < 0.0001). Subcalvarial artifacts were
significantly lower at 120 keV (P < 0.02). Artifacts measured in the posterior
fossa were generally lower at high kiloelectron volt levels; however, no
statistical significance was detected. Virtual monoenergetic images were rated
superior to polyenergetic images in regard to all 4 criteria (P < 0.0001). The
observers reported an optimal radiological assessment of gray-white matter
differentiation at 65 keV and optimal assessment of subcalvarial space at 120
keV. CONCLUSIONS: In comparison to polyenergetic images, virtual monoenergetic
images reconstructed from unenhanced DLCT of the head at 65 keV and 120 keV allow
to optimize gray-white matter contrast and reduce beam hardening artifacts caused
by the skull, respectively.
PMID- 28422807
TI - Clinical Robustness of Accelerated and Optimized Abdominal Diffusion-Weighted
Imaging.
AB - OBJECTIVES: The aim of this study was to assess the robustness of an accelerated
and optimized diffusion-weighted sequence in clinical routine abdominal imaging
using the simultaneous multislice (SMS) technique for scan time reduction and 3
dimensional (3D) diagonal diffusion mode to optimize image quality. MATERIALS AND
METHODS: One hundred fifty consecutive patients received clinically indicated
magnetic resonance imaging for abdominal imaging including an optimized SMS
diffusion-weighted sequence (DWIOPT: diffusion mode 3D diagonal; SMS factor 2;
scan time 1:44 minutes). A subgroup of 41 patients additionally received a
standard diffusion-weighted sequence as reference (DWISTD: diffusion mode 4-scan
trace; scan time 2:35 minutes). Qualitative and quantitative image parameters of
DWISTD and DWIOPT were assessed and compared interindividually within the
subgroup using dedicated statistics. RESULTS: In all patients, image quality
ratings in DWIOPT were rated very high (overall image quality, 4.6 [4-5]; contour
sharpness of right/left hepatic lobe, 4.6 [4-5]/4.4 [4-5]; and lesion
conspicuity, 4.5 [4.5-5]). Interindividually, DWIOPT proved superior to DWISTD in
comparison of overall image quality (4.6 [4.6-4.7] vs 4.2 [4.1-4.2]; P = 0.025)
and contour sharpness of the right/left hepatic lobe (4.6 [4.5-4.7]/4.3 [4.0-4.3]
vs 4.3 [4.1-43]/4.0[3.0-4.0]; each P = 0.045); lesion conspicuity was comparable
in DWIOPT and DWISTD (4.0 [4.8-5] vs 4.4 [4-5]; P = 0.461), and apparent
diffusion coefficient (ADC) values showed no statistically significant difference
(ADCOPT vs ADCSTD: right hepatic lobe, P = 0.084; kidney, P = 0.445). Interreader
agreement was substantial with a kappa value of 0.78 (P < 0.001). CONCLUSIONS:
Diffusion-weighted imaging of the abdomen can be considerably accelerated and
optimized integrating the SMS technique and a 3D diagonal diffusion mode. In a
large patient cohort, this approach proved of superior image quality while
maintaining similar ADC values compared with standard DWI. This technique seems
applicable for daily clinical routine.
PMID- 28422808
TI - Diagnosis of Chronic Intestinal Pseudo-obstruction and Megacystis by Sequencing
the ACTG2 Gene.
AB - OBJECTIVES: The diagnosis of chronic intestinal pseudo-obstruction has depended
on clinical features, manometry, and imaging. This report aimed to determine the
efficacy of sequencing the actin gamma-2 (ACTG2) gene for diagnosis. In addition,
the goal was to determine how often a mutation would be found in our randomly
collected cohort of probands and those probands published previously. METHODS:
Whole exome sequencing was performed in 4 probands with chronic intestinal pseudo
obstruction. Subsequently, only the ACTG2 gene was sequenced in another 24
probands (total 28). We analyzed published data of 83 probands and our 28 (total
111) and determined how many had pathogenic variants and the precise genotype.
RESULTS: Whole exome and Sanger sequencing revealed a pathogenic variant in the
ACTG2 gene in 4 out of 28 of our probands and in 45 out of 83 published probands
(49/111 [44.1%]). Moreover, a mutational hotspot in the ACTG2 gene was
recognized. Genetic heterogeneity is evident. CONCLUSIONS: Pooled gene sequencing
results from 1 individual in each of 111 families enabled a precise diagnosis of
an ACTG2 mutation in 49 (44%). The benefit to patients and families of early
confirmation of a motility disorder not only helps avoid unnecessary
intervention, but also enables institution of appropriate treatments and
avoidance of secondary disorders such as malnutrition and poor growth. Knowledge
of a pathogenic variant in a parent, with a 50% risk of recurrence, provides an
opportunity for genetic counseling.
PMID- 28422809
TI - Associations Between Dietary Intake Before 6 Months of Age and Rapid Weight Gain
Among HIV-exposed Uninfected Infants.
AB - INTRODUCTION: HIV-exposed, uninfected (HEU) infants are potentially at risk for
cardiovascular disease due to in utero exposures. Feeding practices of the infant
could compound this risk. Few studies have, however, evaluated dietary intake of
HEU infants. We determined dietary factors associated with rapid weight gain
(RWG) among HEU infants from birth to 6 months followed at the University of
Miami HIV Screening Program. METHODS: In this cross-sectional analysis, logistic
regression was used to determine dietary factors associated with RWG defined as a
>0.67 SD change in weight-for-age z score from birth to assessment (0.3-6
months). Other covariates included demographics, birth, maternal and gestational
characteristics, and antiretroviral exposures. RESULTS: A total of 86 full-term
HEU infants with a mean age of 3.4 months (SD 1.8 months) were included in this
analysis. Fifty-five percent of mothers were obese. Overall, 39.5% of infants
exhibited RWG. A significant association between consumption of infant cereal and
RWG (odds ratio, 3.52; 95% confidence interval, 1.02-12.10) was found after
adjusting for birth weight, current age, and energy intake. Those infants who
consumed the highest tertile of protein were less likely to gain weight rapidly
after adjusting for the same covariates (odds ratio, 0.15; 95% confidence
interval, 0.02-0.94). CONCLUSIONS: Overall differences in weight gain during
early infancy are at least partly explained by means of infant feeding in young
HEU infants in the United States. Dietary counseling for families of HEU should
reinforce current feeding practice recommendations of the American Academy of
Pediatrics.
PMID- 28422812
TI - Randomized Double-blind Trial of Ringer Lactate Versus Normal Saline in Pediatric
Acute Severe Diarrheal Dehydration.
AB - OBJECTIVE: The aim of this study was to compare the effectiveness of Ringer
lactate (RL) versus normal saline (NS) in the correction of pediatric acute
severe diarrheal dehydration, as measured by improvement in clinical status and
pH (>=7.35). METHODS: A total of 68 children ages 1 month to 12 years with acute
severe diarrheal dehydration (World Health Organization [WHO] classification)
were randomized into RL (n = 34) and NS groups (n = 34) and received 100 mL/kg of
the assigned intravenous fluid according to WHO PLAN-C for the management of
diarrheal dehydration. The primary outcome was an improvement in clinical status
and pH (>=7.35) at the end of 6 hours. Secondary outcomes were changes in serum
electrolytes, renal and blood gas parameters, the volume of fluid required for
dehydration correction excluding the first cycle, time to start oral feeding,
hospital stay, and cost-effectiveness analysis. RESULTS: Primary outcome was
achieved in 38% versus 23% (relative risk = 1.63, 95% confidence interval 0.80
3.40) in RL and NS groups, respectively. No significant differences were observed
in secondary outcomes in electrolytes, renal, and blood gas parameters. None
required second cycle of dehydration correction. Median (interquartile range)
time to start oral feeding (1.0 [0.19-2.0] vs 1.5 [0.5-2.0] hours) and hospital
stay (2.0 [1.0-2.0] vs 2.0 [2.0-2.0] days) was similar. The median total cost was
higher in RL than NS group ((Equation is included in full-text article.)120
[(Equation is included in full-text article.)120-(Equation is included in full
text article.)180] vs (Equation is included in full-text article.)55 [(Equation
is included in full-text article.)55-(Equation is included in full-text
article.)82], P <= 0.001). CONCLUSION: In pediatric acute severe diarrheal
dehydration, resuscitation with RL and NS was associated with similar clinical
improvement and biochemical resolution. Hence, NS is to be considered as the
fluid of choice because of the clinical improvement, cost, and availability.
PMID- 28422813
TI - New Approach in Assessing Core Muscle Endurance Using Ratings of Perceived
Exertion.
AB - George, JD, Tolley, JR, Vehrs, PR, Reece, JD, Akay, MF, and Cambridge, EDJ. New
approach in assessing core muscle endurance using ratings of perceived exertion.
J Strength Cond Res 32(4): 1081-1088, 2018-This study sought to develop
regression models to estimate maximal endurance time using data from 4 core
muscle endurance tests. Eighty healthy university students (age: 22.7 +/- 1.9
years) performed the plank, right side-bridge, left side-bridge, and back
extension tests in a random order. Participants were instructed to hold each
static position for a maximal endurance time, while maintaining proper form, and
then rest for 5 minutes between tests. A test administrator recorded
participants' ratings of perceived exertion (RPE; a modified 10-point scale)
every 5 seconds. Based on regression analysis, the elapsed time to reach an RPE
of 8 (RPE8) exhibited statistical significance (p < 0.0001) and the highest
accuracy as compared with lower RPE values. The following univariate regression
models were generated to estimate maximal endurance time across the 4 tests:
plank (r = 0.94; standard error of estimate [SEE] = 17.6 seconds; n = 77) = 23.9
+ (1.110 * RPE8); right side-bridge (r = 0.92; SEE = 11.4 seconds; n = 80) = 18.5
+ (1.022 * RPE8); left side-bridge (r = 0.93; SEE = 10.8 seconds; n = 80) = 16.8
+ (1.062 * RPE8); and back extension (r = 0.93; SEE = 14.2 seconds; n = 79) =
21.5 + (1.027 * RPE8). These results suggest that submaximal protocols based on
elapsed time to reach RPE8 provide strength and conditioning professionals
relatively accurate univariate regression equation estimates of maximal core
muscle endurance time and offer a viable submaximal alternative to maximal
capacity testing when time efficiency, participant safety, or certain educational
objectives may be a priority.
PMID- 28422814
TI - The Effect of Rubric-Guided, Focused, Personalized Coaching Sessions and Video
Recorded Presentations on Teaching Skills Among Fourth-Year Medical Students: A
Pilot Study.
AB - PROBLEM: As medical students become residents, teaching becomes an expected and
integral responsibility. Yet, training-for-teaching opportunities are lacking. In
2014, the authors designed a pilot study using rubric-guided, focused,
personalized coaching sessions and video-recorded presentations to improve
student teaching skills among fourth-year students at Harvard Medical School.
APPROACH: In 2014-2015, the authors recruited students from an elective on how to
tutor preclinical students for the pilot, which consisted of four phases: a
precoaching teaching presentation, a 30- to 45-minute coaching session, a
postcoaching teaching presentation, and blinded reviewer ratings. Students' pre-
and postcoaching presentations were video recorded. Using a scoring rubric for 15
teaching skills, students rated their pre- and postcoaching videos. Blinded
reviewers also rated the pre- and postcoaching presentations using the same
rubric with an additional category to gauge their overall impression. OUTCOMES:
Fourteen students completed all four phases of the pilot. Students' ratings
demonstrated statistically significant improvement in several teaching skills,
including presentation content (P < .001), rate of speech (P = .001), and opening
statement and learning objectives (P = .004). Blinded reviewers' ratings
demonstrated statistically significant improvements in several teaching skills,
including opening statement and learning objectives (P < .001), overall
impression (P = .001), and conclusion and summary of learning objectives (P =
.004). Students provided largely positive comments on the interventions. NEXT
STEPS: The authors will work toward addressing limitations in the rubric, using
coaching in different teaching settings, addressing the interventions'
generalizability, training coaches, and performing additional evaluations.
PMID- 28422815
TI - No Time for Silence: An Urgent Need for Political Activism Among the Medical
Community.
AB - Despite being a major stakeholder in the U.S. health care system, the medical
community has remained relatively mute in the debate over the future of the
Patient Protection and Affordable Care Act (ACA). If the ACA were repealed, tens
of millions of Americans would be in danger of losing their insurance, resulting
in a significant increase in mortality. Because misinformation about the ACA is
rampant, it is imperative that health care providers explain to the public what
exactly the ACA is and how repeal will affect patients. Traditionally, many in
the medical community have abstained from political advocacy for multiple
reasons, including compromising the doctor-patient relationship, financial
incentives, lack of experience with activism due to an absence of training in
that area, and fear of political retaliation. Encouragingly, there are
indications that the medical community is beginning to become more vocal. Medical
students are one example, having formed a grassroots response to repeal. However,
students need more guidance and support from experienced mentors to most
effectively serve as patient advocates. This is no time for silence: On this life
or-death issue, the medical community cannot afford to remain mute.
PMID- 28422816
TI - Why Not Wait? Eight Institutions Share Their Experiences Moving United States
Medical Licensing Examination Step 1 After Core Clinical Clerkships.
AB - The majority of medical students complete the United States Medical Licensing
Examination Step 1 after their foundational sciences; however, there are
compelling reasons to examine this practice. This article provides the
perspectives of eight MD-granting medical schools that have moved Step 1 after
the core clerkships, describing their rationale, logistics of the change,
outcomes, and lessons learned. The primary reasons these institutions cite for
moving Step 1 after clerkships are to foster more enduring and integrated basic
science learning connected to clinical care and to better prepare students for
the increasingly clinical focus of Step 1. Each school provides key features of
the preclerkship and clinical curricula and details concerning taking Steps 1 and
2, to allow other schools contemplating change to understand the landscape. Most
schools report an increase in aggregate Step 1 scores after the change. Despite
early positive outcomes, there may be unintended consequences to later scheduling
of Step 1, including relatively late student reevaluations of their career choice
if Step 1 scores are not competitive in the specialty area of their choice. The
score increases should be interpreted with caution: These schools may not be
representative with regard to mean Step 1 scores and failure rates. Other aspects
of curricular transformation and rising national Step 1 scores confound the data.
Although the optimal timing of Step 1 has yet to be determined, this article
summarizes the perspectives of eight schools that changed Step 1 timing, filling
a gap in the literature on this important topic.
PMID- 28422817
TI - Incidence and Implications of Left Ventricular Distention During Venoarterial
Extracorporeal Membrane Oxygenation Support.
AB - Left ventricular distention (LVD) during venoarterial extracorporeal membrane
oxygenation (VA-ECMO) support is increasingly recognized but seldom reported in
the literature. The current study defined LVD as not present (LVD-); subclinical
(LVD+, evidence of pulmonary edema on chest radiograph AND pulmonary artery
diastolic blood pressure greater than 25 mm Hg within the first 2 hours of
intensive care unit admission); or clinical (LVD++, need for decompression of the
left ventricle immediately following VA-ECMO initiation). Among 226 VA-ECMO
device runs, 121 had sufficient data to define LVD retrospectively. Nine patients
(7%) developed LVD++ requiring immediate decompression, and 27 patients (22%) met
the definition of LVD+. Survival to discharge was similar among groups (LVD++:
44%, LVD+: 41%, LVD-: 44%). However, myocardial recovery appeared inversely
related to the degree of LVD (LVD++: 11%, LVD+: 26%, LVD-: 40%). When death or
transition to device was considered as a composite outcome, event-free survival
was diminished in LVD++ and LVD+ patients compared with LVD-. Multivariable
analysis identified cannulation of VA-ECMO during extracorporeal cardiopulmonary
resuscitation (ECPR) as a risk factor for decompression (odds ratio [OR]: 3.64,
confidence interval [CI]: 1.21-10.98; p = 0.022). Using a novel definition of
LVD, the severity LVD was inversely related to the likelihood of myocardial
recovery. Survival did not differ between groups. Extracorporeal cardiopulmonary
resuscitation was associated with need for mechanical intervention.
PMID- 28422818
TI - Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability
of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after
Chronic Constriction Injury to the Sciatic Nerve.
AB - BACKGROUND: Inhibition of the metabotropic glutamate receptor subtype 1 in the
anterior cingulate cortex has an analgesic effect during sustained nociceptive
hypersensitivity. However, the specific changes in different subtypes of anterior
cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of
metabotropic glutamate receptor subtype 1 inhibition on different neuronal
subtypes, have not been well studied. METHODS: Retrograde labeling combined with
immunofluorescence, whole cell clamp recording, and behavioral tests combined
with RNA interference were performed in a rat model of chronic constriction
injury to the sciatic nerve. RESULTS: Commissural layer 5 pyramidal neurons
(projecting to the contralateral cortex) existed in the anterior cingulate
cortex. The voltage-gated potassium channel subunit 2-mediated current in these
neurons were substantially reduced after chronic constriction injury (current
densities at +30 mV for the sham, and chronic constriction injury neurons were
[mean +/- SD] 10.22 +/- 3.42 pA/pF vs. 5.58 +/- 2.71 pA/pF, respectively; n = 11;
P < 0.01), which increased the spike width and fast afterhyperpolarization
potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate
receptor subtype 1 alleviated the down-regulation of voltage-gated potassium
channel subunit 2 currents (current density increased by 8.11 +/- 3.22 pA/pF; n =
7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2
current in the commissural neurons attenuated the analgesic effect of
metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05).
CONCLUSIONS: The effect of metabotropic glutamate receptor subtype 1 inhibition
on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely
different with the modification of previously studied hyperpolarization
activated/cyclic nucleotide-gated channel-dependent neurons but relies on the
alteration of voltage-gated potassium channel subunit 2 currents. These results
will contribute to a better understanding of the therapeutic role of metabotropic
glutamate receptor subtype 1 in chronic pain.
PMID- 28422819
TI - GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression,
Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery.
AB - BACKGROUND: Angiotensin II receptor type 1-mediated activation of the alpha
subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and
may promote hypertrophy-induced myocardial damage. The authors recently
identified a TT(-695/-694)GC polymorphism in the human Gq promoter, the GC allele
being associated with an increased prevalence of cardiac hypertrophy. In this
article, the authors tested whether the TT(-695/-694)GC polymorphism is
associated with differences in (1) myocardial Gq protein expression, (2) vascular
reactivity, and (3) myocardial damage after coronary artery bypass grafting.
METHODS: Gq protein expression was measured in right atrial muscle from 55
patients undergoing coronary artery bypass grafting as were skin perfusion
changes (n = 18; laser Doppler imaging), saphenous vein ring vascular reactivity
(n = 50, organ bath) in response to angiotensin II, and myocardial damage (227
patients undergoing coronary artery bypass grafting), as assessed by
postoperative cardiac troponin I concentration. RESULTS: Myocardial Gq expression
was greater in GC/GC genotypes (GC/GC vs. TT/TT: 1.27-fold change; P = 0.006).
Skin perfusion after intradermal angiotensin II injection decreased only in GC/GC
genotypes (P = 0.0002). Saphenous vein rings exposed to increasing angiotensin II
concentrations showed an almost doubled maximum contraction in GC/GC compared
with individuals with the TT/TT genotype (P = 0.022). In patients undergoing
coronary artery bypass grafting, baseline cardiac ejection fraction was different
(GC/GC: 55 +/- 13%; GC/TT: 54 +/- 14%; TT/TT: 48 +/- 15%; P = 0.037) and
postoperative peak cardiac troponin I was greater in patients with the GC/GC
(11.5 +/- 13.8 ng/ml) than in patients with the GC/TT (9.2 +/- 9.2 ng/ml) or
patients with the TT/TT genotype (6.6 +/- 4.8 ng/ml, P = 0.015). CONCLUSIONS: The
GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased
Gq protein expression, augmented angiotensin II receptor type 1-related
vasoconstriction, and increased myocardial injury after coronary artery bypass
grafting, highlighting the impact of Gq genotype variation.
PMID- 28422820
TI - Comparison of the ETView Single Lumen and Macintosh laryngoscopes for
endotracheal intubation in an airway manikin with immobilized cervical spine by
novice paramedics: A randomized crossover manikin trial.
AB - CONTEXT: Management of the airway of a trauma victim is considered challenging.
Various approaches have been described to achieve airway control in this setup;
many of them include video-assited viewing of the larynx during intubation.
ETView Single Lumen (SL) is a novice single-use endotracheal tube equiped with a
video camera and a light source at its distal tip. Its use was previously
described in seeral clinical and training setups. OBJECTIVE: The aim was to
evaluate the efficacy of the VivaSight SL compared with classic direct
laryngoscopy performed with a Macintosh blade in a manikin-simulated trauma setup
presenting various degrees of airway challenge when performed by inexperienced
physicians. DESIGN, SETTING, PARTICIPANTS: This was prospective, randomized,
crossover, manikin trial. After short training on the ETView system, 67 novice
paramedics attempted to perform oral intubation using both standard direct
laryngoscopy (MAC group) and the VivaSight SL endotracheal tube (ETView group) in
a randomized order on manikins in 3 increasingly more difficult scenarios (simple
intubation, cervical spine manual stabilization, and with cervical collar in
place). OUTCOME MEASURE: Overall success rate, time to intubation, number of
intubation attempts, laryngeal view grade, dental compression, and overall
participant satisfaction were monitored. RESULTS: Duration of intubation and
number of attempts were significantly superior in the ETView group in the latter
2 more challenging scenarios. All other parameters showed superiority to the
ETView group in all 3 scenarios. CONCLUSION: The VivaSight SL system performed
better in a complex scenario of airway management of a trauma victim in need for
cervical spine stabilization performed by novice caregivers compared to standard
direct laryngoscopy and should be considered in this clinical setup.
PMID- 28422821
TI - How the cognitive reserve interacts with beta-amyloid deposition in mitigating
FDG metabolism: An observational study.
AB - This observational study had the aim to assess the interaction between cognitive
reserve (CR) and cerebrospinal fluid beta-amyloid1-42 (Abeta1-42) in modulating
brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism
in patients with moderate Alzheimer disease (AD).Twenty-seven patients with
probable AD and 25 neurological normal subjects (NNS) entered the study. All
participants had an FDG-PET scan, and AD patients also received a lumbar puncture
to measure Abeta1-42, 181p-tau, and Tau concentrations. Based on years of formal
education, AD patients were classified as highly educated-AD (years of formal
education >5) or less educated-AD (years of formal education <5). By using a
voxel-wise approach, we first investigated differences in the cerebral glucose
uptake between AD and NNS, then we assessed the interaction between level of
education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET
metabolism in the patient groups.Significantly lower glucose uptake was observed
in the posterior cingulate gyrus, in the precuneus, in the inferior and medial
temporal gyrus, and in the inferior parietal lobule of AD patients compared with
NNS. A significant interaction was found between CR and Abeta1-42 values on brain
metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients
with higher CR level and marked signs of neuropathology showed glucose
hypometabolism in regions typically targeted by AD pathology. This finding
supports the hypothesis that CR partially compensates for the effect of Abeta
plaques on cognitive impairment, helps in patients' clinical staging, and opens
new possibilities for the development of nonpharmacological interventions.
PMID- 28422822
TI - Intraoperative centration during small incision lenticule extraction (SMILE).
AB - To evaluate intraoperative decentration from pupil center and kappa intercept
during small incision lenticule extraction (SMILE) and its impact on visual
outcomes.This was a retrospective noncomparative case series. A total of 164 eyes
that underwent SMILE at the Singapore National Eye Center were included. Screen
captures of intraoperative videos were analyzed. Preoperative and 3 month
postoperative vision and refractive data were analyzed against decentration.The
mean preoperative spherical equivalent (SE) was -5.84 +/- 1.77. The mean
decentration from the pupil center and from kappa intercept were 0.13 +/- 0.06 mm
and 0.47mm +/- 0.25 mm, respectively. For efficacy and predictability, 69.6% and
95.0% of eyes achieved a visual acuity (VA) of 20/20 and 20/30, respectively,
while 83.8% and 97.2% of eyes were within +/-0.5D and +/-1.0D of the targeted SE.
When analyzed across 3 groups of decentration from the pupil center (<0.1 mm, 0.1
0.2 mm, and >0.2 mm), there was no statistically significant association between
decentration, safety, efficacy, and predictability. When analyzed across 4 groups
of decentration from kappa intercept (<0.2 mm, 0.2-<0.4 mm, 0.4-<0.6 mm, and
>=0.6 mm), there was a trend toward higher efficacy for eyes with decentration of
kappa intercept between 0.4 and <0.6 mm (P = .097). A total of 85.4% of eyes in
the 0.4 to <0.6 mm group had unaided distance VA of 20/20 or better, as compared
to only 57.8% of eyes in >=0.6 mm group.Decentration of 0.13 mm from the pupil
center does not result in compromised visual outcomes. Decentration of greater
than 0.6 mm from the kappa intercept may result in compromised visual outcomes.
There was a trend toward better efficacy in eyes which had decentered treatment
from 0.4 to <0.6 mm from the kappa intercept. Patients with a large kappa
intercept (>0.6 mm) should have their lenticule created 0.4 to 0.6 mm from the
kappa intercept and not close to the pupil.
PMID- 28422823
TI - Association between ALDH2 Glu487Lys polymorphism and the risk of esophageal
cancer.
AB - OBJECTIVE: A meta-analysis was carried out to further evaluate the relationship
between ALDH2 Glu487Lys polymorphism and esophageal cancer risk. METHODS: A total
number of 15 studies that included 3812 cases and 7376 controls were identified
for our meta-analysis. RESULTS: Our findings indicated that individuals with the
combination of Glu/Lys and Lys/Lys genotype had an increased risk of getting
esophageal cancer (GA + AA vs. GG: odds ratio [OR] 1.36, 95% confidence interval
[CI] 0.93-2.00, P = 0.113) with a shift pattern. Although Lys/Lys genotype
carriers showed areduced esophageal cancer risk (AA vs. GA + GG: OR 0.41, 95% CI
0.23-0.72, P = 0.002). Similarly, a negative association was observed under
homozygote comparison (AA vs. GG: OR 0.49, 95% CI 0.29-0.85, P = 0.011). In the
China subgroup analysis, the similar results were found. CONCLUSIONS: This meta
analysis concluded that there was a strong association between ALDH2 Glu487Lys
polymorphism and the risk of esophageal cancer. It further confirmed that ALDH2
Glu487Lys polymorphism was a high-risk factor for esophageal cancer.
PMID- 28422824
TI - Pancreatic carcinoids (serotonin-producing pancreatic neuroendocrine neoplasms):
Report of 5 cases and review of the literature.
AB - INTRODUCTION: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare
tumors representing 1% to 2% of all pancreatic neoplasms. These tumors can
secrete a variety of biologically active substances giving rise to distinct
clinical symptoms or can be clinically nonfunctioning. Apart from insulinomas and
gastrinomas, which constitute the majority of functioning pNENs, some tumors may
secrete serotonin presenting with the features of the carcinoid syndrome. These
so-called pancreatic carcinoids are considered relatively rare tumors and are
associated with increased urinary levels of 5-hydroxyindoleacetic acid (5-HIAA).
It has recently been suggested that the prevalence of such tumors might be
underestimated. CASES: We present a series of 5 patients from our database of 138
pNENs (5/138, 3.62%), harboring serotonin-producing pNENs and describe their
distinctive clinical, biochemical, histopathological features, and response to
treatment along with a review of the relevant available literature. CONCLUSION:
Such tumors are considered rare, although this may be an underestimate as
systematic screening for the presence of serotonin in tissue or elevated urinary
5-HIAA levels in patients with apparently nonfunctioning pNENs is not currently
recommended. In order to reach such a consensus, data from large prospective
studies are needed in order to evaluate the impact of this type of tumors in
survival and clinical outcome, since some studies have suggested a worse
prognosis.
PMID- 28422825
TI - Interdigitating dendritic cell sarcoma presenting in the sigmoid colon mesentery:
A case report and literature review.
AB - RATIONALE: Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare
disease. It commonly occurs in middle-aged males and mainly involves the lymph
nodes. Pathological examination plays an important role in differentiating from
other tumors, but far less published literature focuses on the imaging
characteristics of IDCS. PATIENT CONCERNS: Here, we reported a case of IDCS in a
52-year-old male involving the pelvis with medical imaging and pathologic
findings. DIAGNOSES: Preoperative unenhanced CT scan revealed a 6.0 * 6.3 * 8.0
cm mass with density equal to that of adjacent muscle, located in the pelvis. On
contrast-enhanced CT images, the tumor presented apparent homogeneous
enhancement. CT angiography showed that the tumor was supplied by the branches of
inferior mesenteric artery. Pelvic magnetic resonance imaging manifested a
lobulated solid mass with low signal on T1-weighted and intermediate to high
signal on T2-weighted images. Simultaneously, significantly high signal intensity
was exhibited on the diffusion-weighted images. This patient underwent operative
resection of the tumor. The pathologic diagnosis was IDCS. INTERVENTIONS: This
patient underwent operative resection of the tumor. The resection margins were
negative for the neoplastic proliferation and no distant metastases were found.
The patient did not receive advanced radiotherapy or chemotherapy. OUTCOMES:
Three months after surgery, the follow-up CT scan did not reveal any recurrence
or metastases. LESSONS: This case adds to the experience with IDCS by summarizing
its characteristics as well as reviewing the literature.
PMID- 28422826
TI - Idiopathic hypoparathyroidism with extensive intracranial calcification in
children: First report from Saudi Arabia.
AB - RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial
calcifications outside the basal ganglia (BG) is extremely rare with less than 10
cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with
tetany with otherwise normal neurological and other body system examination
diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further
investigations revealed hyperphosphatemia and undetectable serum intact
parathyroid hormone. Brain computed tomography revealed BG and extensive brain
calcifications. He has no dysmorphic features, vitiligo, mucocuataneous
manifestations, or hair loss. He had normal hemoglobin, electroencephalogram, and
skeletal survey, with negative autoantibodies to alpha and omega interferons and
negative genetic testing for Glial Cell Missing 2 (GCM2) and calcium-sensing
receptors (CaSRs) excluding known causes of hypoparathyroidism. OUTCOMES: This
case presents a rare entity of idiopathic hypoparathyroidism with extensive
intracranial calcification, not only in BG but also outside the extrapyramidal
system with normal mentality, development, pubertal achievement, and neurological
examination. To our knowledge, this is the first report from Saudi Arabia in
pediatrics. LESSONS: Idiopathic hypoparathyroidism is a diagnosis of exclusion
after ruling out all known causes of hypoparathyroidism. It is associated with BG
calcifications, but extensive intracranial calcifications outside the BG are
extremely rare.
PMID- 28422827
TI - A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as
undifferentiated pleomorphic sarcoma in the left atrium.
AB - RATIONALE: An intracardiac cystic mass is a rare type of mass found in the left
atrium. The differential diagnosis of an intracardiac cystic mass includes
hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some
tumor types, including myxoma. PATIENT CONCERNS: We present the case of a 68-year
old woman who presented with episodic dyspnea. DIAGNOSES-INTERVENTIONS-OUTCOMES:
Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass
mimicking myxoma. However, in postoperative findings, it was determined that the
mass was actually a hemorrhagic cyst. Eighteen months later, the patient
presented with recurrent exertional dyspnea and TTE revealed the recurrence of a
left atrial mass. Computed tomography showed that the mass extended into the
right atrium, inferior vena cava, and coronary sinus. After re-operation, the
final histological diagnosis was determined to be an undifferentiated pleomorphic
sarcoma in the left atrium. LESSONS: An intracardiac hemorrhagic cyst was
suspected during the operation of a benign-looking LA mass. As such, we recommend
that other rare etiologies be considered and more biopsies be performed when
possible.
PMID- 28422828
TI - Gastrointestinal Mucormycosis of the Jejunum in an Immunocompetent Patient: A
Case Report.
AB - RATIONALE: Gastrointestinal Mucormycosis (GIM) is a kind of opportunistic fungal
infection with poor prognosis. It usually occurs in patients with immune
deficiency. We reported a case of immunocompetent male patient. PATIENT CONCERNS:
This patient was presented as abdominal distension and gastrointestinal bleeding.
DIAGNOSES: A variety of hemostatic methods was ineffective to stop the bleeding.
The patient finally received laparotomy, and the jejunum lesions were found.
INTERVENTIONS: Pathological examination confirmed it to be gastrointestinal
mucormycosis in jejunum. OUTCOMES: However, after systemic anti-fungi therapy,
the patient died of septic shock. LESSONS: The diagnosis mainly relies on
pathological examination. Early diagnosis and early application of systemic
amphotericin B liposome were fundamental for improving the prognosis.
PMID- 28422829
TI - Impact of pain on cognitive functions in primary Sjogren syndrome with small
fiber neuropathy: 10 cases and a literature review.
AB - Primary Sjogren syndrome (pSS) is a chronic systemic autoimmune disease
characterized by xerophthalmia, xerostomia, and potential peripheral or central
neurological involvement. In pSS, the prevalence of cognitive disorders is
generally sparse across literature and the impact of pain on cognitive profile is
unclear. The aim of this study was to determine the relation between pain,
cognitive complaint, and impairment in a very homogenous population of 10 pSS
patients with painful small fiber neuropathy (PSFN) and spontaneous cognitive
complaint. Neurological exam, neuropsychological assessment, clinical evaluation
measuring pain level, fatigue, anxiety, depression, and cognitive complaint were
performed. Our results showed that 100% of patients had cognitive dysfunction
especially in executive domain (80%). The most sensitive test was the Wisconsin
Card Sorting Test (WCST), abnormal in 70% of our population. Moreover, we found
clear cut significant correlations between pain levels and 3 measures of WCST:
the number of errors (R = -0.768, P = .0062), perseverations (R = 0.831, P =
.0042), and categories (R = 0.705, P = .02). In the literature review, the impact
of pain is underexplored and results could be discordant. In a homogeneous cohort
of pSS patients with PSFN, a cognitive complaint seems to be a valid reflection
of cognitive dysfunction marked by a specific executive profile found with the
WCST. In this preliminary study, this profile is linked to the level of pain and
highlights that an appropriate management of pain control and a cognitive
readaptation in patients could improve the quality of life.
PMID- 28422830
TI - Management of the extensive thoracic defects after deep sternal wound infection
with the rectus abdominis myocutaneous flap: A retrospective case series.
AB - Deep sternal wound infection is a severe complication after open heart surgery.
According to the different severity and dimensions of the deep sternal wound
infection, the treatment method is different. In this study, we aimed to describe
our experience with the rectus abdominis myocutaneous flap for large sternal
wound management, especially when 1 or 2 internal mammary arteries were
absent.Between October 2010 and January 2016, a retrospective review of 9
patients who suffered from the extensive thoracic defects after deep sternal
wound infection was conducted. All of these sternal defects encompassed almost
the full length of the sternum after debridement. Defect reconstruction was
achieved by covering with a rectus abdominis myocutaneous flap. When the
ipsilateral or bilateral internal mammary artery had been harvested previously,
we took advantage of the inferior epigastric artery to provide additional blood
supply to the rectus abdominis myocutaneous flap. Thus, this flap had a double
blood supply.There was no recurrent infection in all 9 patients. Three patients
received the rectus abdominis myocutaneous flap with a double blood supply. Flap
complications occurred in 2 patients (22%). One patient who did not have the
double blood supply flap suffered from necrosis on the distal part of the flap,
which was then debrided and reconstructed with a split-skin graft. The other
patient had a seroma at the abdomen donor site and was managed conservatively.
None of the patients died during the hospital stay.This study suggests that the
rectus abdominis myocutaneous flap may be a good choice to repair the entire
length of sternal wound. When 1 or 2 internal mammary arteries have been
harvested, the inferior epigastric artery can be anastomosed to the second
intercostal artery or the internal mammary artery perforator to provide the
rectus abdominis myocutaneous flap with a double blood supply.
PMID- 28422831
TI - Association between diabetes mellitus and subsequent ovarian cancer in women: A
systematic review and meta-analysis of cohort studies.
AB - Epidemiologic studies have suggested that diabetes mellitus (DM) might be
associated with risk of ovarian cancer; however, the results have been
inconsistent. The aim of this study was to determine the relationship between DM
and the incidence of ovarian cancer on the basis of cohort studies.Relevant
studies from PubMed, Embase, and the Cochrane Library until September 2016 were
collected. The summary risk ratio (RR) was used as the effect measure in a random
effects model. Sensitivity analysis, subgroup analysis, and calculation of
publication bias were conducted.Thirteen articles including 14 cohorts comprising
a total of 3708, 313 women and reporting 5534 cases of ovarian cancer were
included. The summary RR suggested that patients with DM had a higher risk of
ovarian cancer than patients without DM (RR: 1.19; 95% confidence interval: 1.06
1.34; P = .004), and no evidence of publication bias was found. The subgroup
analysis indicated a higher incidence of ovarian cancer in patients with DM in
studies published after 2010, studies not conducted in Europe or the United
States, studies that did not adjust for body mass index or smoking status, and
studies with lower Newcastle-Ottawa Scale scores.The present findings indicated
that DM is a risk factor for ovarian cancer, and future large-scale epidemiologic
studies should be performed to evaluate this relation in specific populations.
PMID- 28422832
TI - Two year result of intravitreal bevacizumab for diabetic macular edema using
treat and extend protocol.
AB - To determine the efficacy of the treat and extend (TAE) protocol with
intravitreal bevacizumab (IVB) for managing diabetic macular edema
(DME).Retrospective, single-center study.For this retrospective study, 42 eyes of
42 patients were initially treated with 3 consecutive monthly IVB injections
(loading phase), after which they were selected for different additional
therapies. For the TAE protocol, the baseline treatment interval was selected to
be 8 weeks and was sequentially lengthened by 2 weeks if the central macular
thickness (CMT) was <300 MUm at 2 consecutive examinations.Among the 42 eyes, 8
eyes (19.0%) received the TAE treatment for 2 years. The BCVA was improved
significantly from 0.37 +/- 0.04 before treatment to 0.19 +/- 0.04 logMAR units
at 2 years after the TAE determined IVB injections (P < .05). The ratio of eyes
with a gain of the BCVA by more than 2 lines was 37.5%. The CMT was significantly
reduced from 515.4 +/- 75.5 to 303.6 +/- 45.0 MUm after 2 years (P < .01). The
mean number of TAE injection was 8.8 and the mean injection interval was 11.0
weeks.After the loading phase, 19.0% of patients can be treated with the TAE
protocol. Although significant visual improvements were obtained after the TAE
protocol, it does not apply to every DME case.
PMID- 28422833
TI - Correction of sagittal imbalance in treatment for adult degenerative scoliosis
with thoracic lordosis and lumbar kyphosis: A case report.
AB - RATIONALE: Lumbar degenerative scoliosis (LDS) is a common spinal disease for
senior citizens. However, LDS accompanied with thoracic lordosis and lumbar
kyphosis (LK) is rare in clinic. No reports have reported LDS with thoracic
lordosis and LK. PATIENT CONCERNS: A 54-year-old woman just complained about
sever back pain without any radiculopathy and neurodeficit of low limb for 2
years, Visual Analogue Scale (VAS) for back pain was 9 points and x-ray showed
adult LDS with lordosis angle of 10 degrees from 5th thoracic to 12th thoracic
(T5-T12) and LK angle of 20 degrees . DIAGNOSES: She was diagnosed with adult
degeneration scoliosis (ADS). INTERVENTIONS: The patient underwent posterior
pedicle screw implantation from L1 to S1 levels. OUTCOMES: Two weeks after
surgery, VAS for back pain was 2 points and x-ray showed thoracic lordosis angle
of 6 degrees , lumbar lordosis (LL) of 6 degrees and sagittal vertical axis from
C7 plumb line (SVA) of 77 mm. One year after surgery, VAS for back pain was 1
points and the x-ray showed thoracic lordosis angle of 6 degrees , LL of 20
degrees , and SVA of 36 mm, implying globe spine for this patient tends to
balance. LESSONS: Adult degenerative scoliosis accompanied with thoracic lordosis
and LK is rare. Correcting sagittal imbalance is an effective treatment. The
surgical outcome is satisfactory. Attention should be paid in sagittal balance
for treatment of ADS. We still need further follow-up to observe change of
sagittal parameters.
PMID- 28422834
TI - Feasibility and safety of emergency laparoscopic partial splenectomy: A
retrospective analysis.
AB - The increased awareness of asplenia-related life-threatening complications has
led to the development of parenchyma sparing splenic resections in past few
years. The aim of this study is to retrospectively analyze the feasibility and
safety of laparoscopic partial splenectomy (LPS) in selected emergency
patients.From January 2013 to December 2015, there were 46 emergency patients,
diagnosed with splenic rupture, admitted in our department. Selection criteria
for LPS: (1) Preoperative CT scan revealed single pole rupture without spleen
pedicle injury; (2) BP>90/60 mm Hg and heart rates <120 bpm; (3) No sigh of
multiple organ injury. Eventually, LPS was performed in 21 patients (Group LPS),
while laparoscopic splenectomy (LS) was performed in 20 patients (Group LS).The
main cause of splenic rupture was traffic accident, followed by blunt injury and
high falling injury. Abdominal CT scan showed the mean longitudinal diameter of
spleen of group LPS was 14.2 +/- 1.8 cm (range 12-17 cm), while the size of
remnant spleen was 5.5 +/- 1.2 cm. Between 2 groups, operation time (LPS: 122.6
+/- 17.2 min vs LS: 110.5 +/- 18.7 minutes, P = .117), and intraoperative blood
loss (LPS: 174 +/- 22 mL vs LS: 169 +/- 29 mL, P = .331) were similar. There were
2 patients suffered subsequent unstable vital sign altering during mobilization
when performing LPS. Conversion to LS (2/21, 9.52%) was decided and successfully
completed. Although there was no patient suffered postoperative OPSI or
thrombocytosis events in both groups after 6-month follow-up, the mean platelets
and leukocyte count were significantly lower in group LPS. Splenic regrowth was
evaluated in 20 patients of group LPS. And the mean regrowth of splenic volume
reached 19% (10%-26%).Due to its minimal invasive effect and functional splenic
tissue preservation, LPS may be a safe and feasible approach for emergency
patients. And prospective trials with clear inclusion criteria are needed to
proof the benefit of LPS.
PMID- 28422835
TI - Predictive factors of better outcomes by monotherapy of an antivascular
endothelial growth factor drug, ranibizumab, for diabetic macular edema in
clinical practice.
AB - Intravitreal ranibizumab (IVR) has been approved for treating diabetic macular
edema (DME), and is used in daily clinical practice. However, the treatment
efficacies of IVR monotherapy in real-world clinical settings are not well
known.The medical records of 56 eyes from 38 patients who received their first
IVR for DME between April 2014 and March 2015, and were retreated with IVR
monotherapy as needed with no rescue treatment, such as laser photocoagulation,
were retrospectively reviewed. The clinical course, best-corrected visual acuity
(BCVA), and fundus findings at baseline, before the initial IVR injection, and at
12 months, were evaluated.Twenty-five eyes from 25 patients (16 men; mean age
68.7 +/- 9.8 years) who received IVR in the first eye, or unilaterally, without
any other treatments during follow-up were included. After 12 months, mean
central retinal thickness (CRT), which includes edema, was reduced (P = .003),
although mean BCVA remained unchanged. There was a negative correlation between
individual changes in BCVA (r = -0.57; P = .003) and CRT (r = -0.60; P = .002) at
12 months compared with baseline values. BCVA changes were greater in individuals
with a history of pan-retinal photocoagulation at baseline (P = .026). After
adjusting for age and sex, CRT improvement >100 MUm at 12 months was associated
with a greater CRT at baseline (OR 0.87 per 10 MUm [95% CI 0.72-0.97]; P = .018)
according to logistic regression analyses; however, better BCVA and CRT at 12
months were associated with a better BCVA (r = 0.77; P < .001) and lower CRT (r =
0.41; P = .039) at baseline, respectively, according to linear regression
analyses.IVR monotherapy suppressed DME, and the effects varied according to
baseline conditions. Eyes that had poorer BCVA or greater CRT, or a history of
pan-retinal photocoagulation at baseline, demonstrated greater improvement with
IVR monotherapy. In contrast, to achieve better outcome values, DME eyes should
be treated before the BCVA and CRT deteriorate. These findings advance our
understanding of the optimal use of IVR for DME in daily clinical practice,
although further study is warranted.
PMID- 28422836
TI - Fecal microbiota transplantation is a rescue treatment modality for refractory
ulcerative colitis.
AB - BACKGROUND: Fecal microbial transplantation (FMT) provides to replace beneficial
bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of
the present study was to prospectively investigate the efficacy of FMT by
assessing the clinical and endoscopic response in patients with ulcerative
colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy.
METHODS: In this prospective and uncontrolled study, 30 patients with UC were
included. All medications except mesalazine were stopped 4 weeks before FMT.
Colonoscopy was performed both before and after FMT. To assess the efficacy of
FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL
extracted fresh fecal suspension was administered into the 30 to 40 cm proximal
of terminal ileum of recipients. RESULTS: After FMT, 21 of the (70%) 30 patients
showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and
endoscopic remission at the week 12. Nine patients (30%) were accepted as a
nonresponder at the end of the week 12. There was no significant difference among
donors concerning both the rate of clinical remission and clinical response. No
adverse events were observed in the majority of patients during FMT and 12 weeks
follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea,
vomiting, abdominal pain, diarrhea, and fewer after FMT. CONCLUSION: FMT could be
considered as a promising rescue treatment modality before surgery in patients
with refractory UC. Besides, FMT also appears to be definitely safer and more
tolerable than the immunosuppressive therapy in patients with UC (NCT02575040).
PMID- 28422837
TI - Multilevel cervical disc replacement versus multilevel anterior discectomy and
fusion: A meta-analysis.
AB - BACKGROUND: Cervical disc replacement (CDR) has been developed as an alternative
surgical procedure to anterior cervical discectomy and fusion (ACDF) for the
treatment of single-level cervical degenerative disc disease. However, patients
with multilevel cervical degenerative disc disease (MCDDD) are common in our
clinic. Multilevel CDR is less established compared with multilevel ACDF. This
study aims to compare the outcomes and evaluate safety and efficacy of CDR versus
ACDF for the treatment of MCDDD. METHODS: A meta-analysis was performed for
articles published up until August 2016. Randomized controlled trials (RCTs) and
prospective comparative studies associated with the use of CDR versus ACDF for
the treatment of MCDDD were included in the current study. Two reviewers
independently screened the articles and data following the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis statement. RESULTS: Seven studies
with 702 enrolled patients suffering from MCDDD were retrieved. Patients who
underwent CDR had similar operative times, blood loss, Neck Disability Index
(NDI) scores, and Visual Analog Scale (VAS) scores compared to patients who
underwent ACDF. Patients who underwent CDR had greater overall motion of the
cervical spine and the operated levels than patients who underwent ACDF. Patients
who underwent CDR also had lower rates of adjacent segment degeneration (ASD).
The rate of adverse events was significantly lower in the CDR group. CONCLUSION:
CDR may be a safe and effective surgical strategy for the treatment of MCDDD.
However, there is insufficient evidence to draw a strong conclusion due to
relatively low-quality evidence. Future long-term, multicenter, randomized, and
controlled studies are needed to validate the safety and efficacy of multilevel
CDR.
PMID- 28422838
TI - Opposite chromosome constitutions due to a familial translocation
t(1;21)(q43;q22) in 2 cousins with development delay and congenital anomalies: A
case report.
AB - RATIONALE: Chromosomal rearrangements are the major cause of multiple congenital
abnormalities and intellectual disability. PATIENT CONCERNS AND DIAGNOSIS: We
report 2 first cousins with unbalanced chromosomal aberrations of chromosomes 1
and 21, resulting from balanced familial translocation. Chromosome microarray
analysis revealed 8.5 Mb1q43q44 duplication/21q22.2q22.3 deletion and 6.8 Mb
1q43q44 deletion/21q22.2q22.3 duplication. Among other features, cognitive and
motor development delay and craniofacial anomalies are present in both patients,
whereas congenital heart defect and hearing impairment is only present in patient
carrying 1q43q44 duplication/21q22.2q22.3 deletion. LESSONS: In this report, we
provide detailed analysis of the phenotypic features of both patients as well as
compare our data with previously published reports of similar aberrations and
discuss possible functional effects of AKT3, CEP170, ZBTB18, DSCAM, and TMPRSS3
genes included in the deleted and/or duplicated regions. Partial trisomy
1q/monosomy 21q has only been reported once before, and this is the first report
of partial monosomy 1q/trisomy 21q. The expressed phenotype of mirroring
chromosomal aberrations in our patients supports the previous suggestion that the
dosage effect of some of the genes included in deleted/duplicated regions may
result in opposite phenotypes of the patients.
PMID- 28422839
TI - Unexpected side effect in mCRC: A care-compliant case report of regorafenib
induced hyperammonemic encephalopathy.
AB - RATIONALE: Regorafenib represents a treatment option in heavily pretreated
patients affected by metastatic colorectal cancer (mCRC). Its safety profile is
typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse
events are manageable. PATIENT CONCERNS: A 56 years-old Caucasian man affected by
mCRC with normal hepatic reserve was treated with regorafenib as second-line
treatment. After only 2 days of therapy, the patient presented to the emergency
department due to impairment of both spatial and temporal orientation and motor
function with bradylalia. INTERVENTIONS: Serum ammonia level was 191 mmol/L,
liver function tests and complete blood count were normal. Regorafenib was
withheld and branched chain amino acids and lactulose were administered.
OUTCOMES: Serum ammonia level returned within the normal range, but when
regorafenib was restarted at a lower dose level, a new episode of acute confusion
arised. MAIN LESSON: Discontinuation of regorafenib after confirmation of
hyperammonemia is strongly recommended; reintroduction of the therapy at lower
doses after resolution of symptoms related to hyperammonemic encephalopathy has
to be discouraged.
PMID- 28422840
TI - Case report: A female case of isolated IgG4-related sclerosing cholangitis
mimicking cholangiocarcinoma.
AB - RATIONALE: IgG4-related disease is a newly recognized fibroinflammatory disorder,
characterized by tumefactive lesions, storiform fibrosis and IgG4-positive plasma
cells infiltration. IgG4-related sclerosing cholangitis (IgG4-SC) is the most
common extrapancreatic manifestation of IgG4-related disease, but it is
frequently associated with autoimmune pancreatitis(AIP). Only few case was
reported to be diagnosed with IgG4-SC in the absence of AIP, with a striking male
preponderance. Here we report a female case of isolated IgG4 related sclerosing
cholangitis mimicking cholangiocarcinoma. PATIENT CONCERNS: A 58-year-old woman
complaint of one-month history of jaundice and right upper quadrant discomfort,
and the biliary reconstruction showed full-length wall thickening and segmental
stenosis. DIAGNOSES: Cholangiocarcinoma was then diagnosed. INTERVENTIONS:
Choledochoplasty was performed, followed by Roux-en-Y anastomosis. OUTCOMES:
However, pathological examination revealed IgG4-related sclerosing cholangitis
(IgG4-SC) and the retrospective measurement of serum IgG4 was 346 mg/dL post
operatively. The patient was followed for another nine monthswithout recurrence.
LESSONS: The differential diagnosis between cholangiocarcinoma and IgG4-SC is
challenging due to significant overlap of clinical manifestations, lab tests and
imaging characteristics. However, as an afterthought of this case, typical
cholangiocarcinoma rarely presents full-length wall thickening. What the case
taught us was pre-operative IgG4 measurement for patients with long bile duct
involvement was highly recommended in order to rule out IgG4-SC.
PMID- 28422841
TI - Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with
advanced pancreatic adenocarcinoma.
AB - To evaluate gemcitabine efficacy in advanced pancreatic cancer patients after the
FOLFIRINOX regimen.Patients with locally-advanced or metastatic pancreatic
adenocarcinoma from French and Canadian centers, who were treated with the first
line FOLFIRINOX regimen (FFX L1), followed by gemcitabine monotherapy as a second
line treatment (GEM L2), were retrospectively evaluated. Statistical analyses
were performed on the demographic, toxicity, and response rate data. Overall
survival (OS) and progression-free survival (PFS) were assessed using the Kaplan
Meier method.Seventy-two patients were reviewed (median age of 63.5 years [range,
32-75 years], men [62%], predominantly pancreatic head tumor location [51%] and
metastatic disease [64%] at the time of diagnosis). The objective response rate
to GEM-L2 treatment was 8/72 (11%), and 32 patients (44%) experienced a clinical
benefit from gemcitabine. Four patients had a partial response to GEM-L2,
although they previously showed a progressive response following FFX-L1
treatment. The median OS for the entire cohort was 13.6 months (95% confidence
interval [CI]: 2.0-35). The median PFS of the GEM-L2 group was 2.5 months (95%
CI: 0.2-10.8) with no statistical differences between patients with controlled or
progressive disease on FFX-L1 therapy.Gemcitabine as a second-line treatment for
advanced pancreatic adenocarcinoma after FOLFIRINOX failure showed clinical
benefits in some patients.
PMID- 28422842
TI - The role of renoscintigraphy and surgery in the management of Page kidney: A case
report.
AB - RATIONALE: Page kidney is an uncommon condition that hypertension occurs
secondary to microvascular ischemia and alternation of small-vessel hemodynamics
due to external compression of renal parenchyma and activation of the renin
angiotensin-aldosterone system. There are no specific guidelines for the
management of Page kidney in the literatures. PATIENT CONCERNS: A 17-year-old
teenager who had Fontan procedure for tricuspid and pulmonary atresia in early
childhood suffered from sudden onset of severe left flank pain during cardiac
catheterization procedure. Left renal artery active bleeding with renal
parenchyma compression in association with renin-mediated hypertension led to the
diagnosis of Page kidney. DIAGNOSES: Page kidney was diagnosed in this case.
INTERVENTIONS: Urgent embolization was performed to treat left renal artery
active bleeding. Because of decreased renal function with elevation of serum
creatinine, inadequate blood pressure control with antihypertensive medication,
and poor renal blood flow of left kidney, open drainage of perirenal hematoma was
done 5 days after catheterization procedure. OUTCOMES: After the operation,
glomerular filtration rate improved immediately, and left flank pain and
hypertension resolved at discharge. LESSONS: The choice of the therapies for Page
kidney depended on the clinical presentation of each case. This case pointed out
the significance of renoscintigraphy and surgery in the management of Page
kidney.
PMID- 28422843
TI - Hypoxia-regulated human periodontal ligament cells via Wnt/beta-catenin signaling
pathway.
AB - BACKGROUND: The aim of this study is to investigate the effects of hypoxia on the
proliferation, morphology, migration ability, hypoxia inducible factor (HIF) 1
(HIF-1) expression, and the relationship with Wnt/beta-catenin signaling of human
periodontal ligament cells (hPDLCs) in vitro. METHODS: hPDLCs (4th passage)
cultured by the tissue culture method were randomly assigned to slight (5% O2),
severe hypoxia (1% O2) groups, and the control (21% O2) group, respectively. From
1st to 7th day, the optical density values were detected, and the growth curve
was described. Wound healing assay was done to observe the migration ability of
hPDLCs under various O2 conditions. Then reverse transcription quantitative real
time polymerase chain reaction (RT-qPCR) was used to detect the expression of
cementum-related genes and Wnt signaling pathway-related genes. Further, RT-qPCR,
Western blot, and immunofluorescence staining method were constructed to show HIF
expressions under different O2 concentrations in hPDLCs. RESULTS: The growth rate
of hPDLCs decreased with the reduction of O2 content by degree, and the
morphology of hPDLCs changed in different O2 contents. Besides, hPDLCs migrate
faster in 21% and 5% O2 than in 1% O2, and both the expressions of cementum
related genes and Wnt signaling pathway-related genes were raised under hypoxic
conditions. In addition, with the reduction of O2 concentration, the messenger
RNA and protein level expression of HIF were all increased, and HIF was gradually
transported from cytoplasm into the nucleus and in 1% O2 concentration, it was
mainly expressed in the nucleus. CONCLUSION: This finding demonstrated that
hypoxia was capable of suppressing the proliferation and migration ability,
changing the morphology of hPDLCs, and stabilizing HIF-1alpha against degradation
and promoting its translocation to the nucleus. Meanwhile, hypoxia may regulate
hPDLCs proliferation and cementogenic differentiation via Wnt/beta-catenin
signaling pathway, which may potentially provide a novel insight into the
etiology and treatment of periodontal diseases.
PMID- 28422844
TI - Ultrasound is helpful to differentiate Bethesda class III thyroid nodules: A
PRISMA-compliant systematic review and meta-analysis.
AB - BACKGROUND: Fine-needle aspiration (FNA) is the most dependable tool to triage
thyroid nodules for medical or surgical management. However, Bethesda class III
cytology, namely "follicular lesion of undetermined significance" (FLUS) or
"atypia of undetermined significance" (AUS), is a major limitation of the US-FNA
in assessing thyroid nodules. As the most important imaging method, ultrasound
(US) has a high efficacy in diagnosing thyroid nodules. This meta-analysis aimed
to assess the role of US in evaluating Bethesda class III thyroid nodules.
METHODS: With keywords "Undetermined Significance," "Bethesda Category III,"
"Bethesda system," "Cytological Subcategory," "AUS/FLUS," "Atypia of Undetermined
Significance," and "Ultrasound/US," papers in PubMed, Cochrane Library, Medline,
Web of Science, Embase, and Google Scholar from inception to December 2016 were
searched. A meta-analysis of these trials was then performed for evaluating the
diagnostic value of thyroid ultrasound in Bethesda Category III thyroid nodules.
RESULTS: Fourteen studies including 2405 nodules were analyzed. According to the
criteria for US diagnosis of thyroid nodules in each article, with any one of
suspicious features as indictors of malignancy, US had a pooled sensitivity of
0.75 (95% CI 0.72-0.78) and a pooled specificity of 0.48 (95% CI 0.45-0.50) in
evaluating Bethesda Class III Nodules. The pooled diagnostic odds ratio was 10.92
(95% CI 6.04-19.74). The overall area under the curve was 0.84 and the Q* index
was 0.77. With any 2 or 3 of US suspicious features as indictors of malignancy,
the sensitivity and specificity were 0.77 (95% CI 0.71-0.83) and 0.54 (95% CI
0.51-0.58), 0.66 (95% CI 0.59-0.73) and 0.71 (95% CI 0.68-0.74), respectively.
CONCLUSIONS: US was helpful for differentiating benign and malignant Bethesda
class III thyroid nodules, with the more suspicious features, the more likely to
be malignant.
PMID- 28422845
TI - Response to benzodiazepines and the clinical course in malignant catatonia
associated with schizophrenia: A case report.
AB - BACKGROUND: Malignant catatonia (MC) is a disorder consisting of catatonic
symptoms, hyperthermia, autonomic instability, and altered mental status.
Neuroleptic malignant syndrome (NMS) caused by antipsychotics is considered a
variant of MC. Benzodiazepine (BZD) medications are safe and effective treatments
providing rapid relief from MC. This case study reports a detailed clinical
course of a case of MC associated with schizophrenia initially diagnosed as NMS
that responded successfully to BZDs but not to dantrolene. CASE PRESENTATION: A
53-year-old man with schizophrenia was admitted to the psychiatric hospital
because of excitement, monologue, muscle rigidity, and insomnia. In the 3 days
before admission, the patient had discontinued his medications after his family
member's death. He presented with hyperthermia, tachycardia, hypertension,
excessive sweating, and an elevated serum creatine phosphokinase (CPK) level. On
the basis of these features, he was suspected to have NMS. The patient was
treated with dantrolene for 7 days without improvement despite having a
normalized serum CPK level. The patient was transferred to our university
hospital for an in-depth examination and treatment of his physical status.
Infection and pulmonary embolism were excluded as possible causes. To treat his
excitement and auditory hallucination, an intravenous drip (IVD) of haloperidol
was initiated, but this treatment increased the patient's catatonic and psychotic
symptoms, although his serum CPK level had remained within a normal range. As a
result, the treatment was changed to diazepam. After an IVD of diazepam, the
patient's symptoms rapidly improved, and the IVD was subsequently replaced with
oral administration of lorazepam. Eventually, the patient was diagnosed with MC
associated with schizophrenia. BZD therapy was dramatically effective.
CONCLUSION: Catatonia, MNS, and MC may be due to a common brain pathophysiology
and these conditions may be in a spectrum, although uncertainty in the boundaries
among conditions, and the BZD treatment may be useful. Most importantly,
catatonia has not been described as a subtype of schizophrenia on the basis of
the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, and
the medications for catatonia and schizophrenia are different. Antipsychotics are
not effective in relieving catatonia, or they may induce NMS, whereas BZDs are
effective for treating both MC and NMS.
PMID- 28422846
TI - Application of remifentanil for conscious sedation and analgesia in short-term
ERCP and EST surgery.
AB - This study aims to observe and evaluate the use of remifentanil in conscious
sedation and analgesia for the safety and comfort of patients undergoing short
term endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic
sphincterotomy (EST).Sixty-eight patients who underwent ERCP and EST were
randomly divided into two groups: research group and control group. Patients in
the research group were intravenously injected with remifentanil (80-2/3* age)
for 1 to 2 minutes, combined with the intravenous injection of propofol (20-30
mg) during the course of treatment. ERCP surgery was performed when Ramsay
sedation scale (RSS) score reached 2-3. During the surgery, patients were closely
monitored for cough symptoms, aspiration, and respiratory and circulatory system
performance, and timely treatment was performed. Sedative drugs were not given in
patients in the control group.In research group, the circulatory and respiratory
depression of patients was mild, only one patient needed to be treated, and there
was no arrhythmia requiring treatment. Five patients had respiratory depression
(blood oxygen saturation decreased to <90%), which was immediately corrected.
There were no interruptions during surgery due to body movement, cough, or
aspiration.The use of remifentanil for conscious sedation and analgesia can be
broadly applied in short-term ERCP, which greatly improves patient comfort during
the surgery. This approach may bear promise for a widespread use in future
clinical practice.
PMID- 28422847
TI - Correlation between Calpain-10 single-nucleotide polymorphisms and obstructive
sleep apnea/hypopnoea syndrome with ischemic stroke in a Chinese population: A
population-based study.
AB - BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common chronic
disorder which is followed by various complications. Calpain-10 belongs to a
commonly expressed member of the Calpain-like cysteine protease family, which
acts as risk marker for some diseases. The purpose of this study is to elucidate
correlation between Calpain-10 single-nucleotide polymorphisms (SNPs) and the
incidence of OSAHS followed by ischemic stroke (IS). METHODS: OSAHS patients were
divided as OSAHS + IS, OSAHS, and control groups, respectively.
Immunohistochemistry was performed for Calpain-10 protein expression, polymerase
chain reaction (PCR)-restriction fragment length polymorphism for detection of
gene polymorphisms of SNP 43 and SNP 19, and PCR-allele specific amplification
for SNP 44. Polysomnography was conducted to check the nocturnal polysomnography
indicators, and also Montreal Cognitive Assessment (MoCA), Scientific Data System
scores cognition and anxiety of patients, respectively. Logistic analysis was
used for the risky factors for OSAHS. RESULTS: Calpain-10 protein expression was
significantly increased in the OSAHS + IS and OSAHS groups compared with the
control group. Significant differences in SNP 43 and SNP 44 genotype, and also
allele frequency were observed in 3 groups, among which the OSAHS + IS group had
higher SNP 43 and SNP 44 allele frequency than the control and OSAHS groups.
There were differences regarding apnea-hypopnea index, minimum fingertip blood
oxygen saturation (LSaO2 [%]), oxygen reduction index (ODI) between patients with
different genotypes of SNP 43 and SNP 44 in OSAHS patients, and also GC and AT
frequency in the OSAHS + IS and OSAHS groups. As compared with the OSAHS group,
the MoCA scores and MoCA subitems in the OSAHS + IS group were declined, whereas
the Scientific Data System scores were elevated. Additionally, GG 43 genotype,
high apnea-hypopnea index, and body mass index were detected as the risk factors
of OSAHS. CONCLUSION: These findings indicate that the Calpain-10 SNP 43 may be
related to OSAHS with IS, with SNP 43 GG genotype as a risk factor for OSAHS with
IS.
PMID- 28422848
TI - Teriparatide as a nonoperative treatment for tibial and femoral fracture
nonunion: A case report.
AB - RATIONALE: Fracture nonunion is a great challenge for orthopedic surgeons. Many
surgical interventions are associated with significant pain and heavy economic
burden. Therefore, our aim was to evaluate the outcomes of a new nonoperative
treatment for fracture nonunion. PATIENT CONCERNS: A 44-year-old man suffered
closed fractures of the right tibia and left femur. Eleven months after surgery,
there was no radiographic healing between fracture fragments. DIAGNOSES: Fracture
nonunion of the right tibia and left femur. INTERVENTIONS: The patient received
systemic treatment with teriparatide (recombinant human Parathyroid Hormone 1-34)
20 MUg/d for 8 months, with further observation at 4 months after
discontinuation. During treatment, bone metabolic markers were measured to
evaluate metabolic activity of osteoblasts and osteoclasts. The Ethics Committee
of Qilu Hospital of Shandong University approved this study. OUTCOMES:
Satisfactory healing of fracture nonunion was obtained without further
intervention. LESSONS: Anabolic treatment with teriparatide showed a positive
effect on healing of fracture nonunion. Evaluation of bone metabolic markers
during treatment is necessary to observe the curative effect. In view of the
positive effect of teriparatide on healing of fracture nonunion in numerous
animal models and clinical studies, it may be a promising alternative treatment
for fracture nonunion in patients who are not suitable for surgical intervention.
PMID- 28422849
TI - Temporal trends in centralization and racial disparities in utilization of high
volume hospitals for lung cancer surgery.
AB - Racial disparities have been suggested in hospital utilization and outcome for
lung cancer surgery, but the effect of hospital centralization on closing this
gap is unknown. We hypothesized that centralization has increased the utilization
of high- or very-high-volume (HV/VHV) hospitals, a proxy for access to high
quality care, over the study period independently from race.Inpatient records
were extracted from the New York Statewide Planning and Research Cooperative
System database (1995-2012) according to Clinical Modification of the
International Classification of Diseases, 9th Revision diagnosis codes 162.* and
165.* and surgical procedure codes 32.2-32.6 (n = 31,931). Patients treated
exclusively with surgery of black or white race with a valid zip code were
included. Logistic models were performed to determine factors associated with
utilization of HV/VHV or low- or very-low-volume (LV/VLV) hospitals; these models
were subsequently stratified by race.The percentage of both black and white
patients utilizing HV/VHV hospitals increased over the study period (+22.7% and
13.9%, respectively). The distance to the nearest HV/VHV hospital and patient
hospital distance were significantly lower in black compared to white patients,
however, blacks were consistently less likely to use HV/VHV than whites (odds
ratioadj: 0.26; 95% confidence interval: 0.23-0.29), and were significantly more
likely to utilize urban, teaching, and lower volume hospitals than whites.
Likelihood of HV/VHV utilization decreased with an increasing distance from a
HV/VHV hospital, overall and separately for black and white patients.Although
centralization has increased the utilization of HV/VHV for both black and white
patients, racial differences in access and utilization of HV hospitals persisted.
PMID- 28422850
TI - Tuberculosis-associated hemophagocytic lymphohistiocytosis with initial
presentation of fever of unknown origin in a general hospital: An analysis of 8
clinical cases.
AB - The study aimed to investigate the clinical features and prognoses of patients
with tuberculosis (TB) who had secondary hemophagocytic lymphohistiocytosis
(HLH).Patients first presenting with fever of unknown origin, who were ultimately
diagnosed with TB-associated secondary HLH, were assessed retrospectively. We
summarized and analyzed clinical manifestations, laboratory examinations,
diagnoses, treatments, and prognoses of patients using clinical data, outpatient
follow-up, and telephone follow-up in combination with literature review.Among
patients admitted to the hospital with fever of unknown origin in the past 10
years, 371 patients were diagnosed with TB. Among them, 8 cases were diagnosed as
tuberculosis-associated HLH (TB-HLH). The proportion of females among TB-HLH
patients was higher than the proportion of females among TB patients. Within the
same time period, 227 cases met the diagnostic criteria for HLH, among which TB
HLH patients accounted for 3.52% of the cases. None of the 8 TB-HLH patients had
underlying diseases, and a majority of them had short symptom durations, rapid
progression, along with multisystem and multiorgan dysfunctions. Their clinical
manifestations were inconsistent with the typical clinical manifestations and
imaging results characteristic of TB. Compared with patients with TB in our
hospital during the same period, the 8 TB-HLH patients had a higher proportion of
blood-disseminated TB and tuberculous meningitis. Apart from this, the
hematological damage in these patients was higher than the common clinical
manifestations of TB, and they also had a high proportion of respiratory failure.
All 8 TB-HLH patients received antitubercular therapy, and 6 of them were also
treated for HLH. However, their morbidity and mortality were significantly higher
than that for reported cases of TB-HLH cases, both domestically and abroad, which
may be attributed to the fever of unknown origin.Patients with TB-HLH had poor
prognoses and no specific clinical manifestations. Therefore, cases of atypical
TB and severe TB should be carefully monitored to achieve early diagnosis and
early intervention.
PMID- 28422851
TI - Relation between serum myokines and phase II cardiac rehabilitation.
AB - Patients with coronary heart disease or acute myocardial infarction after cardiac
catheterization with stenting referred for phase II cardiac rehabilitation (CR)
were grouped according to their preference. Cardio-pulmonary exercise testing
(CPET) was used to determine oxygen uptake ((Equation is included in full-text
article.)) at peak exercise and anaerobic threshold (AT). The control patients
received counseling only while the experiment group received 36 sessions of CR in
3 to 6 months. Exercise physiology parameters and serum myokines (myostatin,
insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) were measured pre-
and postrehabilitation.There were 29 patients in the experiment group and 10 in
the control group, with no significant differences in baseline parameters. The
experiment group had prominent progress in aerobic capacity and body composition
after CR, but their serum myokine concentrations did not change significantly.
Serum myostatin is positively correlated to peak (Equation is included in full
text article.)pre- and post-training, and pretraining AT (Equation is included in
full-text article.), after adjusting for age, sex, and body composition. Serum
IGF-1 is positively correlated with grip strength before training.Serum myostatin
level is positively correlated to aerobic capacity, and IGF-1 level is positively
correlated to grip strength in cardiac patients receiving CR.
PMID- 28422852
TI - Stage I lung adenocarcinoma: the value of quantitative CT in differentiating
pathological subtypes and predicting growth of subsolid nodules.
AB - The aim of this study was to investigate feasibility of quantitative computed
tomography (CT) measurements in predicting invasiveness and growth of nodular
ground glass opacities (nGGOs).A set of 203 patients (group A) with nGGOs that
were confirmed stage-I adenocarcinomas and 79 patients (group B) with nGGOs that
were completely followed up were included. Lesions diameters, volume (VOL),
maximum (MAX), mean (MEN), and standard deviation (STD) of CT attenuation were
measured. P53 labeling index (LI) was evaluated through immunohistochemistry in
group-A patients. Multivariate linear stepwise regressions were performed based
on group-A lesions to calculate P53-LI prediction from CT measurements. The
receiver operating characteristic (ROC) curve analyses were performed to assess
the performance of P53-LI prediction in predicting invasiveness and growth of
nGGOs. The Cox regression analysis was conducted to identify correlation between
P53-LI Prediction and volume doubling time (VDT) of lesions in group B.Diameter,
VOL, MEN, STD, and the P53 LI showed significant differences between lesions of
different pathological invasiveness (P < .01). By multivariate linear
regressions, MEN and STD were identified as independent variables indicating P53
LI (P < .001); thus, an equation was established to calculate P53-LI Prediction
as: P53LI Prediction = 0.013 * MEN + 0.024 * STD + 9.741 (R square = 0.411, P <
.001). The P53-LI Prediction showed good performance, similar as the actual one,
in differentiating pathological invasiveness of nGGOs. In addition, the P53-LI
Prediction demonstrated excellent performance in predicting growth of nGGOs (AUC
= 0.833, P < .001) and independently forecasted VDT of nGGOs (beta = 1.773, P <
.001).The P53-LI Prediction that was calculated from preoperative quantitative CT
measurements of nGGOs indicates lesions' invasiveness and allows for predicting
growth of nGGOs.
PMID- 28422853
TI - Gastritis in patients undergoing sleeve gastrectomy: Prevalence, ethnic
distribution, and impact on glycemic.
AB - Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese
patients. The aim of this study was to evaluate the presence of Helicobacter
pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy
specimens, and its association to other variables.One hundred six sleeve
gastrectomy specimens were examined histopathologically for the presence of
gastritis and its relation to other factors like ethnicity, glycemic control, and
postoperative complications.Twelve patients had HP gastritis, 39 had non-HP
gastritis, and 55 had normal mucosa. There was a statistical difference between
the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab
patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population
6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic
control was worse in the gastritis group with a mean HbA1c of 8.344% while in the
normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control
reverted to normal in most the diabetic patients. There were few postoperative
complications however, they were not related to HP.There is a high incidence of
gastritis in obese patients. The incidence of gastritis in the Arab population in
our study was higher than that in the Jewish population. The glycemic control
before surgery was worse in patients with gastritis than in the normal mucosa
group. HP bares no risk for postoperative complications after LSG and does not
affect weight loss. However a larger cohort of patients must be studied to arrive
at conclusive results.
PMID- 28422854
TI - Immunohistological analysis of active sacroiliitis in patients with axial
spondyloarthritis.
AB - The sacroiliac joints (SIJs) are one of the most common sites involved in axial
spondyloarthritis (axSpA), and there are few studies on the histopathology of the
SIJ in this group of patients.Mononuclear cell infiltrates in the bone marrow and
fibrous tissue resembling a pannus formation were the pathological features of
early sacroiliitis in our previous study. We undertook a further
immunohistological evaluation of these features in patients with axSpA.Biopsy
specimens from the SIJ of 6 patients with established ankylosing spondylitis (AS)
and 13 patients with nonradiographic axial spondyloarthritis (nr-axSpA) were
analyzed. An immunohistological method was performed to examine the macrophages
(CD163), T cells (CD3), and B cells (CD20).Mononuclear cell infiltrates in the
bone marrow were observed in only 6 patients with nr-axSpA. Fibrous tissue was
observed in all patients with established AS and 9 patients with nr-axSpA.
Macrophage, T cell, and B cell infiltrates could be detected in both the bone
marrow and fibrous tissue. All bone marrow specimens from 6 nr-axSpA patients
exhibited CD163+ macrophage infiltrates; of these, 5 exhibited CD20+ B cell
infiltrates and 3 exhibited CD3+ T cell infiltrates. Among the fibrous tissue
specimens, all exhibited macrophage infiltrates, 9 exhibited B cell infiltrates,
and 4 exhibited T cell infiltrates.In addition to macrophages and T cells, B
cells are also involved in active sacroiliitis in patients with axSpA.
PMID- 28422855
TI - Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after
liver resection.
AB - There is limited information available concerning the effect of thymalfasin
(Talpha1) as an adjuvant therapy in hepatocellular carcinoma (HCC) patient who
received liver resection. The present study aimed to evaluate whether Talpha1 can
improve the prognosis of small HCC patients after liver resection.A total of 206
patients with small HCC who underwent liver resection were analyzed in our
retrospective cohort study. Patients were divided into 2 groups: group A
(resection + Talpha1, n = 44) and group B (resection, n = 162). Clinical data,
overall survival (OS), and recurrence-free survival (RFS) were compared.
Prognostic factors were identified using multivariate analysis.After a median
follow-up of 47.0 months, 134 patients (65%) had recurrence, and 62 patients
(30.09%) died. The 1, 3, and 5-year OS rate of patients in group A was 97.7%,
90.6%, and 82.9%, respectively, and 95.1%, 80.5%, and 62.9%, respectively, for
patients in group B (P = .014). The 1, 3, and 5-year RFS rate of patients in
group A was 70.5%, 56.8%, and 53.3%, respectively, and 65.8%, 41.3%, and 32.1%,
respectively, for patients in group B (P = .015). Multivariate analysis indicated
that Talpha1 was an independent prognostic factor for both OS (P = .015, hazard
ratio 0.349, 95% confidence interval 0.149-0.816) and RFS (P = .019, hazard ratio
0.564, 95% confidence interval 0.349-0.910).Talpha1 as an adjuvant therapy after
liver resection may improve the prognosis of small HCC patients after liver
resection.
PMID- 28422856
TI - A cross-sectional evaluation of meditation experience on electroencephalography
data by artificial neural network and support vector machine classifiers.
AB - To quantitate the meditation experience is a subjective and complex issue because
it is confounded by many factors such as emotional state, method of meditation,
and personal physical condition. In this study, we propose a strategy with a
cross-sectional analysis to evaluate the meditation experience with 2 artificial
intelligence techniques: artificial neural network and support vector machine.
Within this analysis system, 3 features of the electroencephalography alpha
spectrum and variant normalizing scaling are manipulated as the evaluating
variables for the detection of accuracy. Thereafter, by modulating the sliding
window (the period of the analyzed data) and shifting interval of the window (the
time interval to shift the analyzed data), the effect of immediate analysis for
the 2 methods is compared. This analysis system is performed on 3 meditation
groups, categorizing their meditation experiences in 10-year intervals from
novice to junior and to senior. After an exhausted calculation and cross
validation across all variables, the high accuracy rate >98% is achievable under
the criterion of 0.5-minute sliding window and 2 seconds shifting interval for
both methods. In a word, the minimum analyzable data length is 0.5 minute and the
minimum recognizable temporal resolution is 2 seconds in the decision of
meditative classification. Our proposed classifier of the meditation experience
promotes a rapid evaluation system to distinguish meditation experience and a
beneficial utilization of artificial techniques for the big-data analysis.
PMID- 28422857
TI - Serum resistin positively correlates with serum lipids, but not with insulin
resistance, in first-degree relatives of type-2 diabetes patients: an
observational study in China.
AB - To investigate whether serum resistin correlated with hypertension, obesity,
dyslipidemia, or insulin resistance (IR) in Chinese type 2 diabetes mellitus
(T2DM) patients and their first-degree relatives (DFDRs) in a case-control
observational study.We determined the serum levels of resistin, plasma lipids,
glucose, and insulin, and performed clinical assessments of hypertension,
obesity, and IR for 42 T2DM patients, 74 of their DFDRs, and 51 healthy control
participants with no family history of T2DM (NC group). The biochemical and
clinical variables were compared between the 3 groups, and relationships between
serum resistin and the other variables were evaluated using a Pearson correlation
analysis.Significant trends were observed in the triglyceride, HbA1c, and
resistin levels, in which the values observed in the DFDR group were intermediate
to those of the T2DM and NC groups (P < .05 for all). A stratified analysis
revealed significant trends in the resistin level and scores for homeostasis
model assessment (HOMA) indexes for IR and insulin sensitivity in women and in
the HbA1c and resistin levels in men (P < .05 for all), with DFDR subjects
exhibiting intermediate values. The Pearson analysis showed that serum resistin
positively correlated with total cholesterol and low-density lipoprotein
cholesterol in the DFDR group only (P < .05 for both), and that resistin did not
correlate significantly with HOMA indexes, blood glucose, insulin, HbA1c,
triglyceride, high-density lipoprotein cholesterol, BMI, waist or hip
circumference, or blood pressure.Our results suggest that elevated serum resistin
might contribute to an increased risk of hyperlipidemia in DFDRs of Chinese T2DM
patients.
PMID- 28422858
TI - 350-560 MUm gelatin sponge particles combined with transcatheter arterial
chemoembolization for the treatment of elderly hepatocellular carcinoma: The
safety and efficacy.
AB - To retrospectively analyze the safety and efficacy of 350-560 MUm gelatin sponge
particles combined with single-chemotherapy drug transcatheter arterial
chemoembolization (Gs-TACE) for the treatment of elderly hepatocellular carcinoma
without surgical resection.Thirty elderly hepatocellular carcinoma patients
without surgical resection, who received Gs-TACE in our hospital, were selected.
Slowly injected gelatin sponge particles (350-560 MUm)+ 10 mg lobaplatin
injection into the regional embolization tumor target vessel. The Response
Evaluation Criteria for Solid Tumors could be used to evaluate the tumor response
after intervention surgery.Eighty-nine times of intervention TACE were conducted
on the 30 patients. The average size of tumor was 8.3 cm. The median survival
time was 28 months, and the 1 and 2-year survival rates were 89% and 58%,
respectively. The Response Evaluation Criteria for Solid Tumors was used to
evaluate the tumor response, and found that the complete response, partial
response, and OR were 30%, 56.67%, and 86.67%, respectively, at 1 month after
intervention surgery. The patients were divided into groups: 60 to 65 years age
group (A), >65 to 75 years age group (B), and >75 years age group (C); the median
survival times were 16, 32, and 33 months, respectively, and there was
statistical difference between A group, B group, and C group. The analysis of
prognosis factors showed that there was statistical significance in age,
Barcelona Clinic Liver Cancer stage, portal vein invasion, and alpha fetal
protein (AFP), and age was the protective factor.Gelatin sponge particles (350
560 MUm), combined with transcatheter arterial chemoembolization, provide an
alternative method for the treatment of elderly hepatocellular carcinoma without
surgical resection.
PMID- 28422859
TI - The levels of triglyceride and total cholesterol in methamphetamine dependence.
AB - The serum triglyceride (TG) and total cholesterol (TC) levels have been reported
altered in the traditional drug-dependence (such as marijuana and heroin).
However, studies assessing the relationships among serum TC, TG, and
methamphetamine (MA)-dependence have not been described well. In this study, our
aim is to explore the serum TG and TC levels in large sample of MA-dependent
patients. A retrospective study was conducted in 938 MA-dependent patients who
were recruited between February 2, 2008 and March 11, 2013, with social
characteristics and drug-dependence history (duration of MA use, routes of drug
administration, and daily dose were collected). Then, the serum levels of TC, TG,
glucose (GLU), body mass index (BMI), and blood pressure were measured among the
participants. Meanwhile, 985 age- and gender-matched healthy people in the
physical examination center were selected as control group. Compared with the
control group, significant decreases of TC, TG, GLU, and BMI were observed in MA
dependent patients (P < 0.05). Besides, we found that the daily dose of MA use
was associated with TC (beta = -0.079, P = 0.015) and the duration of MA use was
independently related to BMI (beta = -0.071, P = 0.031). This study demonstrated
that the levels of TC, TG, GLU, and BMI factors altered in the MA-dependent
patients. In addition, there is a negative association between MA dependence and
TC and BMI.
PMID- 28422860
TI - Primary spinal glioblastoma multiforme: A case report and review of the
literature.
AB - RATIONALE: Primary spinal glioblastoma multiforme (GBM) is a rare clinical entity
with an aggressive course and an invariably dismal prognosis. Its clinical
characteristics, radiologic and pathologic findings, and treatment protocols have
been discussed in a few cases. PATIENT CONCERNS: A 15-year-old female was
admitted to the neurology department with a chief complaint of progressive
numbness and weakness in her left upper extremity for 3 months and neck pain for
1 month. DIAGNOSES: Spinal magnetic resonance imaging showed an intramedullary
expansile mass localized between C4 and C7. The diagnosis of GBM was determined
on the basis of the histopathological findings after operation. INTERVENTIONS:
Laminotomy and laminoplasty between C4 and C7 were performed, and the tumor was
partially resected. The patient was administered focal adjuvant radiotherapy
concomitantly with oral chemotherapy following the surgery. OUTCOMES: With severe
neurologic deficits at 13 months after the diagnosis, the patient expired.
LESSONS: Although therapeutic options have been improving, the prognosis of the
primary spinal GBM remains poor. The treatment of primary spinal GBM entered into
a central registry and multiple-center cooperation is important in establishing
future therapeutic strategies.
PMID- 28422861
TI - Does long-term efficacy differ between infliximab and adalimumab after 1 year of
continuous administration?: A STROBE-compliant retrospective cohort study.
AB - Although biologics are important inflammatory bowel disease therapies, loss of
response (LOR) remains problematic. We evaluated LOR to biologics in our Crohn
disease (CD) patients receiving biologics. Of 137 biologic-treated CD patients,
68 continuously receiving the same biologic type for at least 1 year were divided
into 2 groups: infliximab (IFX) (n = 39) and adalimumab (ADA) (n = 29). Clinical
courses were compared at biologic introduction and at 1 year. Both groups were
retrospectively analyzed for LOR at and beyond 1 year after biologic introduction
(study endpoint). Patients were then divided into LOR and non-LOR groups to
identify factors predicting LOR. At 1 year after biologic introduction, decreases
in CD activity index were 94 +/- 105 in the IFX and 102 +/- 89 in the ADA group,
not significantly different. Blood test data did not differ between these groups.
LOR occurred in 14 IFX and 5 ADA group patients. Event-free rates at 5 years
after biologic introduction were 62% in the IFX and 61% in the ADA group.
Patients achieving clinical remission 1 year after biologic introduction
accounted for 69% of the IFX and 90% of the ADA group, while respective rates of
secondary LOR at 5 years were 32% and 26%. C-reactive protein (CRP) at biologic
introduction (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.04-2.06; P =
.02) and age at CD onset (OR, 1.1; 95% CI, 1.01-1.20; P = .03) predicted LOR. As
to IFX and ADA efficacies after 1 year of administration, there were no
significant differences in event-free rates for the 5 years after biologic
introduction or the secondary LOR rate. CRP at biologic introduction and age at
CD onset predicted LOR.
PMID- 28422862
TI - Prevalence of abnormally invasive placenta among deliveries in mainland China: A
PRISMA-compliant Systematic Review and Meta-analysis.
AB - BACKGROUND: Abnormally invasive placenta (AIP) or placenta accreta (PA) is
considered numerous adverse maternal and fetal-neonatal complications. There has
been no detailed study to characterize the prevalence of AIP among deliveries in
mainland China. OBJECTIVES: We aimed to fill this gap and obtained overall and
regional estimates of AIP prevalence via a systematic review and meta-analysis.
METHODS: This systematic review and meta-analysis was totally performed following
the Meta-analysis of Observational Studies in Epidemiology guidelines for
systematic reviews of observational studies, and the Preferred Reporting Items
for Systematic reviews and Meta-Analysis statement for reporting systematic
reviews and meta-analysis. RESULTS: A total of 23 articles (including 350,939)
were included. Most studies (22) focused on the placenta increta (PI), only 2
articles in PA, and none in placenta percreta (PP). In this meta-analysis, the
overall prevalence of AIP was 0.22% (95% confidence interval 0.18%-0.27%) in a
heterogeneous set of studies (I = 93.5%). In a subgroup, the prevalence of PA and
PI was 0.48% and 0.23%, respectively. Stratified analyses of PI found that the
prevalence was similar in North (0.23% [0.14%-0.32%]) and South (0.23% [0.15%
0.32%]), and lower in Central (0.20% [0.09-0.31%]); the inlanders (0.17% (0.12%
0.23%]) had a lower prevalence of PI than those living in coastal areas (0.24%
[0.35%-0.63%]). As time goes on, the prevalence, from 0.03% (0.02%-0.04%) in 1970
to 1979 to 0.48% (0.30%-0.66%) in 2010 to present, was higher and higher. The
different prevalence was also found in different in maternal age groups.
CONCLUSIONS: This first systematic review and meta-analysis found that the
prevalence differed among different geographic areas and maternal age groups. The
results would be useful for the design of abnormally invasive placenta planning
and implementation adequate health care systems and treatment programs in
mainland China.
PMID- 28422863
TI - Risk factors and prognosis of pulmonary embolism in patients with lung cancer.
AB - Malignant tumors are often complicated with venous thrombosis and pulmonary
embolism (PE), particularly in lung cancer. However, owing to the limited data
regarding the clinical course about PE in lung cancer patients, the aim of this
study is to analyze the risk factors and prognosis of patients with PE and lung
cancer. We performed a retrospective case-control study, the clinical data of 90
patients in the First Affiliated Hospital of People's Liberation Army General
Hospital between Jan 2010 and Jan 2015 were analyzed, including 30 lung cancer
patients with PE (PE group), 60 lung cancer patients without PE (non-PE group),
treated during the same period. Logistic regression analysis was applied to
explore risk factors of PE. Patient survival was also compared with matched
controls via a log-rank test. The multivariate analysis revealed that
adenocarcinoma, stage III to IV, high D-dimer, and low PaO2 were independent risk
factors. The survival time in patients with PE was remarkably lower than that in
patients without PE (P < .0005). Adenocarcinoma, stage III to IV, high D-dimer
and low PaO2 are important risk factors for lung cancer patients with PE. PE
suggested a poor prognosis in lung cancer patients.
PMID- 28422864
TI - Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does
affect IL-2/IFN-gamma expression of T cells in vitro?: A prospective, randomized,
double-blind study.
AB - BACKGROUND: Ketamine has been used as an analgesic adjuvant with morphine in the
treatment of refractory cancer pain recently. But both morphine and ketamine have
been reported to produce a number of immunomodulatory effects. The current study
was performed to assess whether the concentration of ketamine, as adjuvant
analgesics for patient with refractory cancer pain, was related to its effect on
T cells interleukin-2 (IL-2)/interferon-gamma (IFN-gamma) expression in vitro.
METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from venous
blood of patients with refractory cancer pain over a Ficoll-Hypaque density
gradient. T cells were isolated from by positive selection using anti-CD3 beads.
T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group),
morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1,
MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28.
Then supernatant IL-2 and IFN-gamma protein analysis, quantitative reverse
transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-gamma were
done. RESULTS: There were no significant difference of supernatant IL-2 and IFN
gamma among C group, M group, and MK1 group, but the mRNA of M group and MK1
group were decreased compared with C group (P < .05). Compared with C group, both
of the supernatant protein and the mRNA of MK5 group and MK10 group were all
significantly decreased (P < .01). Compared with M group, both of the supernatant
protein and the mRNA of MK5 group and MK10 group were all decreased (P < .05),
while supernatant IL-2 and the mRNA of MK10 group were significantly decreased (P
< .01). CONCLUSION: In conclusion, we confirmed that just as morphine, ketamine
dose-dependently suppressed IL-2 and IFN-gamma of activated T lymphocyte of
patients with refractory cancer pain in vitro, but the inhibitory action of low
dose ketamine could be neglected.
PMID- 28422865
TI - Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia: A
clinical case report.
AB - RATIONALE: Crystalglobulinemia is a rare disease caused by monoclonal
immunoglobulins, characterized by irreversible crystallization on refrigeration.
It causes systemic symptoms including purpura, arthralgia, and vessel occlusive
conditions to be exacerbated by exposure to cold. We report a patient with
crystalglobulinemia associated with monoclonal gammopathy of undetermined
significance (MGUS) manifesting as chronic arthralgia and recurrent acute
arterial occlusion. PRESENTING CONCERNS: A 61-year-old man, who had been
diagnosed with MGUS and who had arthralgia of unknown origin, presented with
recurrent acute limb ischemia after surgical thromboembolectomy. Refrigeration of
his serum formed precipitates that looked like needle-shaped crystals. These
crystals did not dissolve with warming, which is not a characteristic of
cryoglobulins. Skin biopsy results showed crystal-liked eosinophilic bodies in
small vessels and we diagnosed crystalglobulinemia. INTERVENTION AND OUTCOMES:
Although he underwent above-knee amputation, he was treated with a bortezomib and
dexamethasone-based chemotherapeutic regimen, following lenalidomide maintenance
therapy. Finally, he achieved complete remission and serum crystalglobulins
diminished. LESSONS: Monoclonal gammopathy, previously diagnosed as MGUS, can
cause systemic symptoms and thrombotic conditions by producing pathologic
immunoglobulins, such as crystalglobulins. In such situations, MGUS, even when it
has not progressed to multiple myeloma, can be a target of aggressive
chemotherapy. Crystalglobulinemia should be considered for patients with
monoclonal gammopathy manifesting as systemic and thrombotic symptoms exacerbated
by cooling.
PMID- 28422866
TI - The use of anticoagulants for prevention and treatment of osteonecrosis of the
femoral head: A systematic review.
AB - BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive disease,
which mainly affects young adults and often necessitates total hip arthroplasty
(THA), so early interventions are critical to successfully protect hip joint from
THA. In this review, our purpose was to determine the effects of anticoagulants
for preventing and treating the primary and secondary ONFH, respectively, before
the collapse stage or before the pathology of necrosis. METHODS: We searched
PubMed, Embase, Web of Science databases for relevant studies. Any observational
or experimental studies that evaluated anticoagulants and ONFH were our goal of
searching the electric databases. RESULTS: Four studies including a total of 218
hips were identified in this review, 2 of them were prospective studies which
performed by 1 group, 1 was a retrospective study, and the last was a prospective
comparative study. CONCLUSIONS: Our findings supported that the anticoagulants
could be used for primary ONFH. However, anticoagulants cannot play a protective
role on secondary ONFH. Moreover, there were no serious adverse effects reported
in the studies after anticoagulants treatment. Nevertheless, our present study
with some limitations such as the limited sample size only provided limited
quality of evidence; confirmation from further systematic review or meta-analysis
with large-scale, well-designed randomized control trials is required.
PMID- 28422867
TI - A simple scoring algorithm predicting extended-spectrum beta-lactamase producers
in adults with community-onset monomicrobial Enterobacteriaceae bacteremia:
Matters of frequent emergency department users.
AB - The incidence of community-onset bacteremia caused by extended-spectrum-beta
lactamase (ESBL) producers is increasing. The adverse effects of ESBL production
on patient outcome have been recognized and this antimicrobial resistance has
significant implications in the delay of appropriate therapy. However, a simple
scoring algorithm that can easily, inexpensively, and accurately be applied to
clinical settings was lacking. Thus, we established a predictive scoring
algorithm for identifying patients at the risk of ESBL-producer infections among
patients with community-onset monomicrobial Enterobacteriaceae bacteremia
(CoMEB).In a retrospective cohort, multicenter study, adults with CoMEB in the
emergency department (ED) were recruited during January 2008 to December 2013.
ESBL producers were determined based on ESBL phenotype. Clinical information was
obtained from chart records.Of the total 1141 adults with CoMEB, 65 (5.7%) caused
by ESBL producers were identified. Four independent multivariate predictors of
ESBL-producer bacteremia with high odds ratios (ORs)-recent antimicrobial use
(OR, 15.29), recent invasive procedures (OR, 12.33), nursing home residents (OR,
27.77), and frequent ED user (OR, 9.98)-were each assigned +1 point to obtain the
CoMEB-ESBL score. Using the proposed scoring algorithm, a cut-off value of +2
yielded a high sensitivity (84.6%) and an acceptable specificity (92.5%); the
area under the receiver operating characteristic curve was 0.92.In conclusion,
this simple scoring algorithm can be used to identify CoMEB patients with a high
ESBL-producer infection risk. Of note, frequent ED user was firstly demonstrated
to be a crucial predictor in predicting ESBL-producer infections. ED clinicians
should consider adequate empirical therapy with coverage of these pathogens for
patients with risk factors.
PMID- 28422868
TI - Meta-analysis of possible role of cadherin gene methylation in evolution and
prognosis of hepatocellular carcinoma with a PRISMA guideline.
AB - BACKGROUND: Cadherins (CDHs) have been reported to be associated with cancer.
However, the clinical significance of CDH gene methylation in hepatocellular
carcinoma (HCC) remains unclear. METHODS: Based on the preferred reporting items
for systematic reviews and meta-analyses (PRISMA) statement criteria, available
studies were identified from online electronic database. The overall odds ratio
(OR) and the corresponding 95% confidence interval (95% CI) were calculated and
analyzed. RESULTS: A total of 29 eligible studies with 2562 HCC samples and 1685
controls were included. E-cadherin (CDH1) hypermethylation was observed to be
significantly higher in HCC than in benign, adjacent, or normal samples.
Moreover, CDH1 hypermethylation was not associated with gender, tumor grade,
clinical stage, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection in
HCC patients. H-cadherin (CDH13), protocadherin-10 (PCDH10), P-cadherin (CDH3),
and M-cadherin (CDH15) methylation may have an increased risk of HCC in fewer
than 4 studies, and methylated cadherin 8, type 2 (CDH8) and OB-cadherin (CDH11)
had a similar OR in HCC and adjacent samples. When HCC samples were compared with
normal samples, the analysis of sample type revealed a significantly higher OR in
normal blood samples than in normal tissues for hypermethylated CDH1 (50.82 vs
4.44). CONCLUSION: CDH1 hypermethylation may play a key role in the
carcinogenesis of HCC. However, CDH1 hypermethylation was not correlated with
clinicopathological features. Methylated CDH13, PCDH10, CDH3, and CDH15, but not
methylated CDH8 or CDH11, may lead to an increased risk of HCC. Hypermethylated
CDH1 may become a noninvasive blood biomarker. Further studies with more data are
necessary.
PMID- 28422869
TI - Effects of Jianpi Qingchang decoction on the quality of life of patients with
ulcerative colitis: A randomized controlled trial.
AB - This study aims to determine the effects of the Jianpi Qingchang decoction (JQD)
on the quality of life (QOL) of patients with spleen deficiency and dampness-heat
syndrome ulcerative colitis (UC).A total of 120 active UC patients with spleen
deficiency and dampness-heat syndrome were enrolled into this study. These
patients were randomly divided into 2 groups: test group and control group (n =
60, each group). Patients in the test group were treated with JQD, while patients
in control group were treated with 5-amino salicylic acid. After treatment for 8
weeks, differences in inflammatory bowel disease questionnaire (IBDQ) scores,
short form-36 health survey questionnaire (SF-36) scores, and Sutherland Disease
Activity Index (DAI) values were compared between these 2 groups to assess the
QOL of patients.Sutherland DAI scores decreased in both groups after the
treatment, but the difference was not statistically significant (P < .05).
However, the difference in bowel symptoms, systemic symptoms, total scores of the
4 IBDQ dimensions (physical function, bodily pain, vitality, and mental health),
and total scores of the SF-36 questionnaires between these 2 groups were
statistically significant (P < .05).JQD can be used as supplementary and
alternative therapy to relieve clinical symptoms in patients with mild to
moderate active UC, and consequently improve their QOL.
PMID- 28422870
TI - Case report: The first case of Achromobacter xylosoxidans-related tunnel
infection in a patient receiving peritoneal dialysis.
AB - RATIONALE: Achromobacter xylosoxidans infection is mostly reported in
immunocompromised patients. Until now, it is still rarely reported in patients
undergoing peritoneal dialysis. PATIENT CONCERNS: This is the 1st case of A
xylosoxidans infection due to tunnel infection of a Tenckhoff catheter.
DIAGNOSIS: The diagnosis was confirmed by the report of culture. INTERVENTIONS:
Risk factors for this infection in peritoneal dialysis include uremia with an
immunocompromised state, contamination due to inexperienced skills, and aqueous
environment of the dialysate. OUTCOME: We believe that finding the source of A
xylosoxidans contamination is the most important aspect of the overall treatment
of the infection. LESSONS: Environmental investigation of suspected source
contamination is warranted in those with A xylosoxidans infection. Once the
diagnosis is made, removal of the Tenckhoff catheter should not be delayed.
PMID- 28422871
TI - Ultrasound versus fluoroscopy-guided medial branch block for the treatment of
lower lumbar facet joint pain: A retrospective comparative study.
AB - The aim of this study was to compare the mid-term effects and benefits of
ultrasound (US)-guided and fluoroscopy (FL)-guided medial branch blocks (MBBs)
for chronic lower lumbar facet joint pain through pain relief, functional
improvement, and injection efficiency evaluation.Patients with chronic lumbar
facet joint pain who received US (n = 68) or FL-guided MBBs (n = 78) were
included in this retrospective study. All procedures were performed under FL or
US guidance. Complication frequency, therapeutic effects, functional improvement,
and the injection efficiency of MBBs were compared at 1, 3, and 6 months after
the last injection.Both the Oswestry Disability Index (ODI) and the verbal
numeric pain scale (VNS) improved at 1, 3, and 6 months after the last injections
in both groups. Statistical differences were not observed in ODI and VNS between
the groups (P > .05). The proportion of patients who reported successful
treatment outcomes showed no significant differences between the groups at
different time points. Logistic regression analysis showed that sex, pain
duration, injection methods, number of injections, analgesic use, and age were
not independent predictors of a successful outcome. US guidance was associated
with a significantly shorter performance time.US-guided MBBs did not show
significant differences in analgesic effect and functional improvement compared
with the FL-guided approach. Therefore, by considering our data from this
retrospective study, US-guided MBBs warrant consideration in the conservative
management of lower lumbar facet joint pain.
PMID- 28422872
TI - Effect of HSP27 and Cofilin in the injury of hypoxia/reoxygenation on hepatocyte
membrane F-actin microfilaments.
AB - Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate
the ischemia/reperfusion injury of transplanted organ. Through the study of the
molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the
mechanism of F-actin damage induced by ischemia and reperfusion was studied from
the level of cell and molecule.The hypoxic environment of cells in vitro was
simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R
group was subdivided into 3 subgroups: H/R 2, 4, and 6 h. Changes of cell shape
and the growth state, apoptosis, ultrastructural changes, and the changes in F
actin microfilament content were observed. Heat shock protein 27 (HSP27),
Cofilin, and F-actin gene and protein levels were determined by real-time
polymerase chain reaction and western blot assay, respectively.Cells showed
circular adherence growth under normal circumstances, while the spindle cells and
shedding cells were significantly increased in H/R groups. Apoptosis cells in H/R
group were increased significantly with the extension of hypoxia time. The number
of endoplasmic reticulum was decreased significantly in the H/R group, the
mitochondrion hydropic was degenerated and the glycogen was disappeared. The F
actin fibers in the H/R group were disordered, the morphology of the fibers was
obviously decreased, and the fluorescence staining decreased obviously (P < .05).
The transcription and expression levels of HSP27, Cofilin, and F-actin were
significantly lower than those in the control group (P < .05).These results
demonstrate that H/R can affect the correct assembly of F-actin microfilaments
and weakens the normal cycle of F-actin microfilaments through inhibiting the
protein expression and gene transcription of HSP27 and Cofilin in hepatocytes,
thereby changing the skeleton of F-actin microfilaments.
PMID- 28422873
TI - Clinical features of treatment-naive patients with hepatitis B virus infection: A
community-based survey from high- and intermediate-hepatitis B endemicity regions
in Southeast China.
AB - The aim of study was to investigate the clinical features of treatment-naive
patients in 2 regions with high- and intermediate-hepatitis B endemicity level in
Southeast China and provide the baseline data for monitoring health or planning
therapy.This study included 8207 cases of treatment-naive patients with hepatitis
B virus (HBV) infection from Yuhuan (YH, high-hepatitis B endemicity region) and
Shaoxing (SX, intermediate-hepatitis B endemicity region) during 2014-2015.
Clinical data were collected from the patients. Blood samples were kept for
detecting hepatitis B surface antigen, hepatitis B envelope antigen (HBeAg),
hepatitis B envelope antibody, hepatitis B surface antibody, hepatitis B core
antibody, liver function, HBV deoxyribonucleic acid, and alpha-fetoprotein. All
persons underwent B ultrasound to exclude liver cirrhosis or cancer.Of all 8207
HBsAg-positive patients, 52.9% patients were in the low-replication (LR) stage
and 30.3% in the HBeAg-negative chronic hepatitis B (ENH) stage; 8.8% cases were
in the ENH stage with elevated alanine aminotransferase (ALT). More male than
female patients were in immune clearance (IC) or ENH stages with elevated ALT
(10.4% vs 4.8%, 12.1% vs 5.3%, respectively, P < .05). The percentage of patients
in IC and immune tolerant (IT) stages declined with increasing age, whereas the
percentages of ENH with elevated ALT stage were highest in 40 to 60 years.The
percentage of patients in IT and IC stages was higher in YH than in SX (9.4% vs
3.8%, 9.9% vs 4.2%, respectively, P < .05). More patients had HBVDNA>=10 IU/mL in
YH than in SX (24.6% vs 16.0%, P < .05), and more male than female patients had
HBVDNA>=10 IU/mL(24.5% vs 17.9%, P < .05).Clinical features varied in treatment
naive patients with HBV infection between different genders and regions. More
attention should be paid to the surveillance and therapy of patients in YH
especially male patients for the prevention and prognosis of hepatitis B.
PMID- 28422874
TI - CONSORT the effect of intraoperative dexmedetomidine on hemodynamic responses
during emergence from nasotracheal intubation after oral surgery.
AB - BACKGROUND: Dexmedetomidine provides smooth emergence with reduced agitation. The
authors hypothesized low-dose dexmedetomidine infusion might contribute to
hemodynamic stability during and after nasotracheal tube extubation. METHODS:
Ninety-three adult patients scheduled for oral and maxillofacial surgery were
enrolled in this prospective study. Patients were randomly assigned to receive
normal saline (control group, n = 31), dexmedetomidine at 0.2 MUg/kg/h (DEX0.2
group, n = 31), or dexmedetomidine at 0.4 MUg/kg/h (DEX0.4 group, n = 31). Mean
arterial pressure (MAP), heart rate (HR), and response entropy (RE) and state
entropy (SE) were recorded during emergence from anesthesia. RESULTS: Extubation
times were similar in the 3 groups. Mean MAP was significantly lower at eye
opening (T3) and immediately after extubation (T4) in the DEX0.2 (P = .013 and
.003, respectively) and DEX0.4 group (P = .003 and .027, respectively) than in
the control group. At T3 and T4, mean HR was significantly higher in the control
group than in the DEX0.2 (P = .014 and .022, respectively) or DEX0.4 groups (P =
.003 and <.001, respectively). In the postanesthetic care unit, mean MAP and HR
were significantly lower in the DEX0.2 (P = .03 and .022, respectively) and
DEX0.4 groups (P = .027 and <.001, respectively) than in the control group.
CONCLUSION: Intraoperative dexmedetomidine infusion at rates of 0.2 or 0.4
MUg/kg/h during oral and maxillofacial surgery could provide stable hemodynamic
profiles during anesthetic emergence from nasotracheal intubation without
delaying extubation times.
PMID- 28422875
TI - Jagged1 modulated tumor-associated macrophage differentiation predicts poor
prognosis in patients with invasive micropapillary carcinoma of the breast.
AB - OBJECTIVES: Invasive micropapillary carcinoma of the breast (IMPC) constitutes a
unique and aggressive subtype of breast cancer. We aimed to evaluate the
prognostic significance of the Jagged1 (a ligand of the Notch pathway)
expression, and infiltration density of tumor-associated macrophages (TAMs) in
patients with IMPC. METHODS: Jagged1 expression and CD163+, CD68+ macrophage
infiltration were evaluated by immunohistochemistry in 222 tumor samples, and the
clinical significance was analyzed. mRNA level of Jagged1 was analyzed by real
time PCR in tumor tissues. RESULTS: The IMPC patients showed larger tumor size,
more lymphatic invasion, higher expression levels of estrogen receptor (ER),
increased Ki67 index, higher Jagged1 protein level, and denser infiltration of
CD163+ macrophages compared to patients with invasive breast ductal carcinoma. In
the IMPC cohort, positive Jagged1 expression was related to aggressive features
including large tumor size, lymphatic invasion, and Ki67 overexpression.
Statistical significance was found between CD163+ macrophage infiltration and
Jagged1 expression levels. Cox regression analysis revealed that ER negativity,
positive Jagged1 expression, and a high degree of CD163+ macrophage infiltration
were independent prognostic factors for disease-free survival, and positive
Jagged1 expression was an independent prognostic factor for overall survival. The
level of Jagged1 mRNA was higher in tumor tissues of patients with IMPC.
CONCLUSION: Jagged1, by modulating TAMs infiltration, is associated with a less
favorable prognosis for patients with IMPC. Our results have important
implications for therapies targeting Jagged1-Notch signaling and re-educating
TAMs polarization for patients with IMPC.
PMID- 28422876
TI - Low complication rate of elastic stable intramedullary nailing (ESIN) of
pediatric forearm fractures: A retrospective study of 202 cases.
AB - Elastic stable intramedullary nailing (ESIN) has been established as state of the
art treatment for forearm fractures in children, if operative stabilization is
required. Their use has been expanded to single bone shaft fractures, and also
more complex injuries such as Monteggia fractures or Monteggia-like lesions. A
wide range of complications has been reported in the literature, up to 70% in
certain investigations. The purpose of this study was to assess the complication
rate after ESIN treatment of forearm fractures in children and adolescents in a
representative cohort of patients from a level 1 trauma center in Germany.Between
2000 and 2015, we retrospectively analyzed all patients, up to the age of 16
years, with forearm fractures, who were operatively treated using ESIN in our
department of general and trauma surgery. The main outcome measurements were the
rates of postoperative complications after ESIN such as re-fracture, malunion,
nonunion, tendon lesion, wound infection, and limited range of motion.In all, 201
consecutive patients with 202 forearm fractures were included in this study. Age
averaged 9.7 years (range 3-16 years). Fifteen (7.4%) fractures were open.
Fractures were 82.2% diaphyseal both-bone forearm fractures. Follow-up averaged
10.2 months (range 0.7-176.3 months). Complications were 10 re-fractures, 2
malunions, 3 extensor pollicis longus tendon ruptures, 1 superficial wound
infection, and 2 limited range of motions. Fourteen (6.9%) children required a
secondary operative intervention for their complication. Time to implant removal
averaged 3.8 months (range 0.4-16.3 months).Elastic stable intramedullary nailing
is a minimally invasive and reliable technique with a low complication rate. Both
bone forearm fractures and single bone fractures, and also Monteggia and
Monteggia-equivalent fractures can be successfully treated with this method. As a
major complication, re-fractures are frequently seen, even with ESIN in situ.
PMID- 28422877
TI - Suxamethonium induces a prompt increase in the bispectral index.
AB - Upon inducting general anesthesia in the operating room, we have observed a
prompt increase in the bispectral index (BIS) after the intravenous injection of
suxamethonium. We hypothesized that the cause of this BIS increase is muscle
hyperactivity owing to fasciculation. However, no reports have been published
regarding this abrupt increase in the BIS upon the induction of general
anesthesia by suxamethonium. To investigate the degree of change in the BIS in
patients receiving anesthesia with suxamethonium, we performed a prospective
observational study of 63 participants who underwent closed reduction for nasal
bone fracture. Anesthesia was induced by the total intravenous administration of
anesthetics and 1.5 mg kg of suxamethonium was injected intravenously upon
achieving BIS between 45 and 55. Intubation was performed after fasciculation.
Electromyograms and BIS values were recorded from the induction of suxamethonium
until 15 minutes after intubation. The mean BIS values were 95.4, 48.5, and 69.3
before induction, before the intravenous injection of suxamethonium, and
immediately after fasciculation, respectively. The BIS value immediately after
fasciculation (69.3 +/- 10.6) was significantly higher than the cutoff BIS value
of 60 (P < .001). Although fasciculation after the intravenous injection of
suxamethonium resulted in the prompt increase of the BIS to values over 60, none
of the participants was awake during surgery. In conclusion, the administration
of suxamethonium resulted in the postfasciculation increase of the BIS to an
average value of 69.3 without affecting the patient's state of consciousness.
PMID- 28422878
TI - Microsurgical treatment of carotid-ophthalmic aneurysm associated with multiple
anterior and posterior circulation aneurysms: A case report.
AB - BACKGROUND: The clipping of multiple intracranial aneurysms in 1 stage is
uncommon. In this case, we report clipping of an ophthalmic aneurysm associated
with multiple anterior and posterior circulation aneurysms via the Dolenc
approach. METHODS: The main symptoms of the patient are headache, along with
nausea and vomiting. The patient's arteriogram revealed a wide-necked aneurysm of
the right ophthalmic artery, an irregular aneurysm of the anterior communicating
artery, and a basilar artery aneurysm. The surgical intervention for these
aneurysms is a challenge because of the complex anatomical relationship with the
surrounding structures. The 3 aneurysms, which were not amenable to a single
intervention, were successfully clipped in 1 incision. RESULTS: After surgery,
the patient reported feeling well. One year after surgery, the patient had no SAH
recurrence. CONCLUSIONS: Occasionally, surgical treatment was used even for
aneurysms of the carotid-ophthalmic artery with aneurysms of anterior
communicating artery and basilar artery, which are contraindicated for
interventional therapy.
PMID- 28422879
TI - The clinicopathological features of second primary cancer in patients with prior
breast cancer.
AB - Nowadays, the risk of developing second primary cancers among women diagnosed
with prior breast cancer represents a public health issue worldwide.Twenty-eight
cases of the primary breast cancer with the multiple primary cancers (MPC)
between 2008 and 2015 at our hospital were retrospectively analyzed in regards to
age of patients, family history, interval time of the 2 cancers, and survival
time of these patients.A total 28 cases were analyzed, at the mean age of 44.57
years at the diagnosis of the first primary cancer. The most common primary
cancer in these breast cancer patients was contralateral breast cancer. Of 28
patients with breast cancer, 16 developed a second malignant tumor of the
opposite breast, there were no significant difference both median age at first
breast cancer and second breast cancer (P > .05). The difference of interval time
of 2 cancers also had no statistical significance. There was no statistically
significant difference in overall survival between the bilateral primary breast
cancers (BPBC) group and the group of breast cancer patients who diagnosed with
another cancer (P > .05). If we grouped patients age of diagnosed with the first
cancer (<45, >=45 years), no statistical different between 2 groups (P > .05).
However, the survival time with positive-node patients was lower than in patients
with node-negative, the difference had a notable significant difference (P <
.01). And there are 3 cases had a positive family history for malignant tumor in
the form of first-degree relative.Multiple primary carcinoma in patients with
prior breast cancer is not the influencing factor of prognosis. It is crucial to
detect, diagnose, and treat cancers at their early stage for improving the cure
rate of cancer and the survival rate of patients.
PMID- 28422880
TI - The management and surgical intervention timing of enchondromas: A 10-year
experience.
AB - Enchondroma, reportedly the most common primary tumor of the long bones of the
hand, usually develops during the first till fourth decades of life. However,
there has no consensus been reached regarding the surgical intervention timing
for these patients. We aim to evaluate the optimal surgical intervention timing
for the patients with fractures due to enchondromas, investigate the impact of
pathological fractures on the treatment and outcomes in these patients.Medical
records and X-rays of patients treated for enchondroma of the hand from 2005 to
2015 were retrospectively reviewed. We collected 148 cases in total and 92 of
them had complete information including X-rays, medical records, and files of
follow up.There were no significant differences in terms of consolidation time
after surgery, recurrence rate, and DASH scores between the groups with and
without fractures; the treatment costs were higher in the group with fractures
than those without fractures; however, patients without fractures were able to
resume work earlier than those with fractures.The pathological fractures
associated with enchondromas have no significant impact on the treatment outcomes
compared to those with simple nonfractured enchondromas. Although the cost was
more expensive for patients treated primarily with pathological fractures due to
enchondromas, these patients could resume their work normally much earlier than
those treated by delayed surgery. Early surgical intervention is recommended for
better results and no increased risks for patients with pathological fractures
caused by enchondromas.
PMID- 28422881
TI - Comparison of effects of desflurane and sevoflurane on postoperative nausea,
vomiting, and pain in patients receiving opioid-based intravenous patient
controlled analgesia after thyroidectomy: Propensity score matching analysis.
AB - In this study, we aimed to compare the effect of desflurane and sevoflurane on
postoperative nausea and vomiting and pain in patients receiving opioid-based
intravenous patient-controlled analgesia (IV-PCA) after thyroidectomy.We reviewed
the electronic medical records of 1042 patients administered opioid-based IV-PCA
after a thyroidectomy at Chung-Ang University Hospital between January 1, 2010
and June 30, 2016. We classified the patients into 2 groups according to the
inhalation anesthetic used for anesthesia: desflurane versus sevoflurane (groups
D and S, n = 587 and 455, respectively). Then, propensity scoring was used to
select 234 matched subjects between both groups based on their confounding
factors. A propensity score matching method was used to match patients from the 2
groups in a 1:1 ratio.Before the propensity score analysis, there was no
significant difference between the 2 groups. However, after the propensity score
matching, the frequency of complete remission (CR, defined as no nausea and
vomiting) was significantly higher in group S than it was in group D. The number
of patients administered rescue antiemetics on day 0 in group S was lower than
that in group D, although it was not statistically significant.In patients
receiving opioid-based IV-PCA after thyroidectomy, sevoflurane seems to be more
beneficial in achieving CR than desflurane was. However, further randomized
controlled studies are needed to confirm this conclusion.
PMID- 28422882
TI - Hospital mortality after hip fracture surgery in relation to length of stay by
care delivery factors: A database study.
AB - Two hypotheses were offered for the effect of shorter hospital stays on mortality
after hip fracture surgery: worsening the quality of care and shifting death
occurrence to postacute settings.We tested whether the risk of hospital death
after hip fracture surgery differed across years when postoperative stays
shortened, and whether care factors moderated the association.Analysis of acute
hospital discharge abstracts for subgroups defined by hospital type, bed
capacity, surgical volume, and admission time.153,917 patients 65 years or older
surgically treated for first hip fracture.Risk of hospital death.We found a
decrease in the 30-day risk of hospital death from 7.0% (95%CI: 6.6-7.5) in 2004
to 5.4% (95%CI: 5.0-5.7) in 2012, with an adjusted odds ratio [OR] 0.71 (95%CI:
0.63-0.80). In subgroup analysis, only large community hospitals showed the
reduction of ORs by calendar year. No trend was observed in teaching and medium
community hospitals. By 2012, the risk of death in large higher volume community
hospitals was 34% lower for weekend admissions, OR = 0.66 (95%CI: 0.46-0.95) and
39% lower for weekday admissions, OR = 0.61 (95%CI: 0.40-0.91), compared to 2004.
In large lower volume community hospitals, the 2012 risk was 56% lower for
weekend admissions, OR = 0.44 (95%CI: 0.26-0.75), compared to 2004.The risk of
hospital death after hip fracture surgery decreased only in large community
hospitals, despite universal shortening of hospital stays. This supports the
concern of worsening the quality of hip fracture care due to shorter stays.
PMID- 28422883
TI - Transverse rectus abdominis myocutaneous flap for postpneumonectomy
bronchopleural fistula: A case report.
AB - RATIONALE: Numerous types of flap coverage have been reported to prevent or to
repair bronchopleural fistulas. Most of the flaps were harvested from chest area.
However, these pedicled flaps might not be optimal for the patient who has
undergone previous radiotherapy on pulmonary parenchyma because the pedicle
artery of the flap might have been injured by irradiation. Therefore, an
alternative flap outside of the chest area is necessary. PATIENT CONCERNS: A 61
year-old male was diagnosed of squamous cell carcinoma in right upper lobe lung
(cT3N2M0, stage IIIa). After completing the neoadjuvant chemoradiotherapy, he
underwent video-assisted thoracoscopic surgery with right side intrapericardial
pneumonectomy. DIAGNOSIS: Persistent air leak due to postpneumonectomy
bronchopleural fistula. INTERVENTIONS: Pedicled transverse rectus abdominis
myocutaneous (TRAM) flap was used to repair the bronchial stump. OUTCOMES: The
bronchial stump was repaired successfully, the bronchopleural fistula was
obliterated, and the patient was free from air leak after following for 12
months. LESSONS: This case demonstrated that pedicled TRAM flap is a feasible
alternative to repair bronchopleural fistula.
PMID- 28422884
TI - Posterior reversible encephalopathy syndrome in a postpartum hemorrhagic woman
without hypertension: A case report.
AB - RATIONALE: Posterior reversible encephalopathy syndrome (PRES), which diagnosis
is based on clinical symptoms and radiological features, is a neurotoxic disease
characterized by a set of clinical manifestations, such as seizure, headache,
visual, and/or consciousness disturbance. It is the first case of PRES followed
by postpartum hemorrhage (PPH) without underlying disease. PATIENT CONCERNS: A 37
year-old healthy woman had PPH after caesarean section. Six days after delivery,
headache occurred suddenly, followed by episodes of clonus seizure. DIAGNOSES:
Brain computed tomography showed ischemic stroke. However, magnetic resonance
imaging revealed characteristics consistent with PRES. INTERVENTIONS: The patient
received phenytoin for seizure control. OUTCOMES: Seizure was under good control
over the following days. Three months later, repeated magnetic resonance imaging
showed complete remission. LESSONS: PRES may be triggered by PPH and is not
necessarily secondary to typical predisposing factors such as hypertension or
pre/eclampsia. Hormone fluctuation, increased blood pressure variation, and
massive blood transfusion may be contributed to the development of PRES in our
case. Also, it is necessary to rule out those life-threatening diseases, such as
cavernoma hemorrhage, cerebral venous thrombosis, and ischemic stroke before the
diagnosis of PRES.
PMID- 28422885
TI - Cancer of unknown primary: Registered procedures compared with national
integrated cancer pathway for illuminating external validity.
AB - Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence
and mortality. As primary identification is crucial to choosing treatment,
guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are
complied with, or if they are indeed helpful, is however unclear. We compared
procedures performed in suspected CUP patients with recommendations of national
guidelines to assess external validity of guidelines.The Danish National Patient
Registry (NPR) comprising population data was utilized to identify the suspected
CUP patients during 2009 to 2010 and explore exposure to procedures and patient
survival. The cohort was investigated in terms of validity of diagnosis through
cross-referencing with the Cancer Registry (CR), which served as gold standard
for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of
542 patients (275 males, 264 females) of whom 210 (38.7%) had a CUP diagnosis
confirmed. Within the cohort, 347 patients (64.0%) had a registration in CR
matching with the NPR registration. Exposure to diagnostic procedures included
biopsy (n = 439, 81.0%) and image modalities (n = 532, 98.2%). Survival was poor
with 67 (12.4%) individuals alive after 4 years.The validity of a CUP diagnosis
in NPR was low when using data from CR as reference. More than half the suspected
CUP patients had a previous cancer diagnosis with CUP being the most frequent.
Patients were diagnosed in compliance with guidelines indicating high external
validity, but less than 1 quarter had their primary identified and the 1-year
survival was approximately 20%. Research is needed to develop efficacious methods
for primary detection.
PMID- 28422886
TI - Comparison of T2 and T3 sympathectomy for compensatory sweating on palmar
hyperhidrosis.
AB - BACKGROUND: An otherwise successfully performed endoscopic thoracic sympathectomy
(ETS) to treat palmar hyperhidrosis (PH) often has a serious side effect:
compensatory sweating (CS). This side effect occurs in other parts of the body to
a disturbing extent. The objective of this study is to determine whether there is
a relationship between the level of ETS performed on patients with PH, and the
occurrence and severity of postoperational CS. METHODS: Between January 2014 and
January 2015, ETS procedures were performed on 25 randomly selected consecutive
subjects (group A) at T2 level, and on another 25 subjects (group B) at T3 level,
who all felt severely handicapped due to PH. All subjects were assessed in terms
of their demographic characteristics including gender and age, as well as
postoperative complications, short-term results, side effects, recurrence of
symptoms, and long-term results. RESULTS: The symptoms disappeared in all
subjects in short-term, and no recurrence was seen in their short or long-term
follow-ups. At the end of year one, CS developed at a rate of 12% in group A and
8% in group B, particularly in their back and abdominal regions. The overall
satisfaction with the procedure in year one was 96% in group A and 100% in group
B. CONCLUSION: When an ETS performed at T2 or T3 level for PH involves only the
interruption of the sympathetic chain, with a limitation on the range of
dissection and avoidance of any damage to ganglia, sweating is stopped
completely. No recurrence of PH is encountered, and CS develops only at low rates
and severities.
PMID- 28422887
TI - Epigastric symptoms of gallbladder dyskinesia mistaken for functional dyspepsia:
Retrospective observational study.
AB - Functional dyspepsia (FD) is a constellation of epigastric symptoms originating
in the gastroduodenal region without organic and metabolic cause. However,
similar confounding symptoms can also appear in patients with gallbladder (GB)
dyskinesia. Therefore, symptoms of GB dyskinesia may be mistaken for FD. We aimed
to identify GB dyskinesia as a cause of FD symptoms compatible with the Rome IV
criteria and the need for an evaluation of GB function in patients with FD
symptoms.We investigated information of patients with FD symptoms who underwent a
quantitative Tc-diisoproyl iminodiacetic acid cholescintigraphy (DISIDA scan)
through electronic medical records, and GB dyskinesia was judged to be the cause
of the FD symptoms if the symptoms disappeared as GB function normalized on the
follow-up DISIA scan in patient with decreased GB function on the initial DISIDA
scan.A total of 275 patients underwent a DISIDA scan. Eighteen patients of them
had FD symptoms compatible with the Rome IV criteria. Three were lost after
undergoing a DISIDA scan. Eight had normal GB function, and the other 7 had
decreased GB function on the initial DISIDA scan. In 4 of the 7 patients with GB
dyskinesia, FD symptoms disappeared as GB function normalized. As a result, GB
dyskinesia was the cause of the symptoms in 4 of 18 patients with FD symptoms
compatible with the Rome IV criteria.It is necessary to evaluate GB function in
patients with refractory FD symptoms because the symptoms can be caused by GB
dyskinesia.
PMID- 28422888
TI - 18F-FDG PET/CT for detection of the primary tumor in adults with extracervical
metastases from cancer of unknown primary: A systematic review and meta-analysis.
AB - BACKGROUND: Cancer of unknown primary (CUP) is a heterogeneous group of cancers,
so called when a biopsy from a patient reveals malignancy without giving a clue
to where in the body the primary tumor is located. Whole-body 18-fluorine
fluorodeoxyglucose positron-emission-tomography/computed tomography (18F-FDG
PET/CT) is widely used for diagnosis and staging of most cancers. We hypothesized
that 18F-FDG PET/CT-especially if used early-is suitable for the detection of the
primary tumor in patients with CUP. OBJECTIVE: To assess the ability of 18F-FDG
PET/CT to detect the primary tumor in adult CUP patients. DATA SOURCES:
PubMed/Medline, Embase, and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies
on CUP from extracervical metastases in which every patient had received an 18F
FDG PET/CT scan and at least one 18F-FDG PET/CT-positive finding was confirmed by
biopsy or clinical follow-up. STUDY APPRAISAL: PRISMA and QUADAS-2 were applied.
SYNTHESIS METHODS: The pooled detection rate (DR) of 18F-FDG PET/CT was assessed
with a fixed-effects model. Heterogeneity among studies was assessed with the I
squared statistic. RESULTS: A total of 2953 articles were identified from which N
= 82 were assessed by full text and N = 20, comprising 1942 adult patients, were
included in the study. Median (range) number of patients and DR was N = 72 (21
316) and 36.3% (9.8%-75.3%), respectively. Two-thirds of included studies were
retrospective, and the pooled DR was 40.93% (95% confidence interval: 38.99%
42.87%). There was large heterogeneity between studies (I-squared = 95.9%),
randomization was not applied, CUP diagnosis was not standardized, and workup (if
described) was characterized by multiple testing procedures resulting in a highly
selected, challenging patient group. CONCLUSIONS: Despite great heterogeneity in
diagnostic workup and in studies in general, an overall DR of 40.93% suggests
that upfront application of 18F-FDG PET/CT may have a role in CUP by obviating a
great many futile diagnostic procedures. To what degree 18F-FDG PET/CT used early
in the course of disease may improve the detection rate could not be deducted
from selected articles. A large, prospective, preferably randomized, study on the
potential benefit of using 18F-FDG PET/CT up front in CUP patients is warranted
to judge if and when 18F-FDG PET/CT should be applied in these patients.
PMID- 28422889
TI - An in vitro biomechanical evaluation of an expansive double-threaded bi
directional compression screw for fixation of type II odontoid process fractures:
A SQUIRE-compliant article.
AB - Odontoid process fracture accounts for 5% to 15% of all cervical spine injuries,
and the rate is higher among elderly people. The anterior cannulated screw
fixation has been widely used in odontoid process fracture, but the fixation
strength may still be limited under some circumstances. This study aims to
investigate the biomechanical fixation strength of expansive double-threaded bi
directional compression screw (EDBCS) compared with cannulated lag screw (CLS)
and improved Herbert screw (IHS) for fixation of type II odontoid process
fracture.Thirty fresh cadaveric C2 vertebrae specimens were harvested and
randomly divided into groups A, B, and C. A type II fracture model was simulated
by osteotomy. Then the specimens of the 3 groups were stabilized with a single
CLS, IHS, or EDBCS, respectively. Each specimen was tested in torsion from 0
degrees to 1.25 degrees for 75 s in each of 5 cycles clockwise and 5 cycles
anticlockwise. Shear and tensile forces were applied at the anterior-to-posterior
and proximal-to-distal directions, respectively, both to a maximum load of 45 N
and at a speed of 1 mm/min.The mean torsional stiffness was 0.309 N m/deg for IHS
and 0.389 N m/deg for EDBCS, which were significantly greater compared with CLS,
respectively (0.169 N m/deg) (P < .05 and P < .05). The mean shear stiffness for
the EDBCS was 238 N/mm, which was significantly greater than CLS (150 N/mm) and
IHS (132 N/mm) (P < .05 and P < .05). All 3 screws only partly restored tensile
stiffness, but not significantly.Fixation with the EDBCS can improve the
biomechanical strength for odontoid process fracture compared with CLS and IHS,
especially in terms of torsional and shear stiffness.
PMID- 28422890
TI - An unusual location of gouty panniculitis: A case report.
AB - RATIONALE: Gouty panniculitis, characterised by the deposition of monosodium
urate crystals in subcutaneous tissue, is a rare clinical manifestation of gout.
PATIENT CONCERNS: The case of a 67-year-old man is reported, who presented an
erythematous nodule on the upper part of the right buttock suspicious for an
abscess. This was in the context of chemotherapy for non-Hodgkin's lymphoma.
DIAGNOSES: Histopathologic examination demonstrated gouty panniculitis.
INTERVENTIONS: Because infection was suspected, an incision was performed. The
lesion was found to be densely calcified and friable, without purulent discharge.
Therefore, a surgical en-bloc resection was performed. OUTCOMES: The wound healed
slowly initially due to a combination of malnutrition, chemotherapy and
infection. A wound infection with Enterococcus faecium was treated with
antibiotic therapy (carbapenem for seven days) and local therapy. At 6-week
follow up the wound showed good granulation tissue and was healing well by
secondary intention. The patient was instructed to continue anti-hyperuricaemic
treatment. LESSONS SUBSECTIONS: In patients known to have long-standing
hyperuricaemia and gout with nonspecific subcutaneous erythematous nodules, gouty
panniculitis should be considered.
PMID- 28422892
TI - Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal
tunnel syndrome: A systematic review and meta-analysis: Retraction.
PMID- 28422891
TI - Relationship and associated mechanisms between ambulatory blood pressure and
clinic blood pressure with prevalent cardiovascular disease in diabetic
hypertensive patients.
AB - The present study was to compare the association between ambulatory blood
pressure (ABP) and clinic BP (CBP) with prevalent cardiovascular diseases (CVD);
and the underlying mechanism would also be investigated concurrently.Diabetic
hypertensive patients were enrolled and divided into 2 groups based on presence
of CVD. Twenty-four hour-ABP monitoring was performed and between-group
differences were evaluated and logistic regression analysis was conducted.A total
of 568 diabetic hypertensive patients were enrolled, and the mean age was 60.8
years, male accounted for 67.8%. Mean durations of diabetes mellitus and
hypertension were 6.1 +/- 2.7 and 5.4 +/- 3.3 years, respectively, and 20.6% had
prevalent CVD. Compared to patients without CVD, patients with CVD had
significantly higher body mass index (BMI), plasma aldosterone concentration
(PAC), and serum sodium level. No significant between-group differences in CBP
were observed. However, 24 hour-SBP, daytime-SBP and nighttime-SBP were all
significantly higher in patients with CVD compared to those without CVD. Pearson
correlation analysis showed that BMI was positively correlated with PAC and serum
sodium level. Logistic regression analyses showed that the association between
clinic SBP and DBP with CVD were progressively attenuated to nonsignificant. In
contrast, both ambulatory SBP and DBP were independently associated with CVD.
However, after being further adjusted for PAC, no significant association was
observed between ambulatory SBP and CVD.In diabetic hypertensive patients, ABP is
superior to CBP in relation to CVD. The association between ambulatory SBP and
CVD may be dependent on aldosterone excess.
PMID- 28422893
TI - Do Concussive Symptoms Really Resolve in Young Children?
AB - OBJECTIVES: To examine the frequency and nature of postconcussive symptoms (PCSs)
and behavioral outcomes in young children following mild traumatic brain injury
(mTBI) or concussion. SETTING: Emergency department. PARTICIPANTS: Children aged
2 to 12 years presenting with either a concussion or minor bodily injury
(control). OUTCOME MEASUREMENT: Parent ratings of PCS were obtained within 72
hours of injury, at 1 week, and 1, 2, and 3 months postinjury using a
comprehensive PCS checklist. Preinjury behavior was examined at baseline using
the Clinical Assessment of Behavior, which was readministered 1 and 3 months
postinjury. RESULTS: PCS burden following mTBI peaked in the acute phase
postinjury but reduced significantly from 1 week to 1 month postinjury. Parents
of children with mTBI reported more persistent PCSs up to 3 months postinjury
than trauma controls, characterized mostly by behavioral and sleep-related
symptoms. Subtle increases in problematic behaviors were observed from baseline
(preinjury) to 1 month postinjury and persisted at 3 months postinjury; however,
scores were not classified as clinically "at risk." CONCLUSIONS: A significant
minority of young children experienced persistent PCS and problematic behavior
following mTBI. Care must be taken when assessing PCS in younger children as
method of PCS assessment may influence parental reporting.
PMID- 28422894
TI - Impact of Telephone-Based Problem-Solving Treatment on the Use of Medical and
Psychological Services in the Military.
AB - OBJECTIVE: To explore the impact of problem-solving treatment (PST) for mild
traumatic brain injury in active duty service members on the use of medical and
psychological services. PARTICIPANTS: Service members who had a mild traumatic
brain injury during their last deployment and enrolled in the CONcussion
Treatment After Combat Trauma (CONTACT) study. DESIGN: Secondary analysis of a
randomized clinical trial. Participants were assigned to telephone-based PST, or
e-mailed or mailed education only over the course of 6 months. MAIN MEASURE: Self
reported health service utilization from months 4 through 6 and 10 through 12
after initiation of treatment, using the Cornell Service Index. RESULTS: In
months 4 to 6, participants receiving PST had 6.17 times the odds of an emergency
department visit or hospitalization than those receiving education only (95%
confidence interval = 1.92-19.8; P value = .0023). These estimates, however, were
not significant using a conservative Bonferroni correction (P value threshold <
.0014). There were no other significant differences for other medical or
psychological services received in months 4 to 6 or 10 to 12. CONCLUSION:
Telephone-based PST was designed to complement clinical care, and this study
showed that it may increase emergency department utilization. Future evaluations
of PST with more accurate and complete measures of health service utilization are
needed.
PMID- 28422895
TI - Diffusion Tensor Tractography for Detection of Concomitant Traumatic Brain Injury
in Patients With Traumatic Spinal Cord Injury.
AB - OBJECTIVES: We investigated concomitant traumatic brain injury in patients with
traumatic spinal cord injury (TSCI) who had head trauma history, using diffusion
tensor tractography (DTT). DESIGN: Retrospective survey. PARTICIPANTS: We
recruited 14 consecutive patients with TSCI and coexisting head trauma history at
the time of TSCI and 30 control subjects. METHODS: The corticospinal tract (CST),
corticoreticulospinal tract (CRT), cingulum, and fornix were reconstructed using
DTT, and DTT parameters (fractional anisotropy and fiber volume) and
configuration were estimated. RESULTS: The values of fractional anisotropy and
fiber volume in the CST, CRT, cingulum, and fornix of the patient group were
significantly lower than those of the control group (P < .05). On configurational
analysis of DTT for each tract, the neural tracts for motor function (the CST and
CRT) had more injury than the neural tracts for cognitive function (the cingulum
and fornix). No association between the severity of TSCI and traumatic brain
injury was observed in terms of DTT parameters. CONCLUSIONS: Using DTT, we found
injury of the neural tracts in patients with head trauma history at the time of
TSCI. Our results suggest that brain evaluation using DTT can be recommended for
the patients with head trauma history at the time of TSCI irrespective of the
results of conventional brain MRI.
PMID- 28422896
TI - Predictors of Sleep Outcomes Following Mild Traumatic Brain Injury in
Preschoolers: Subjective and Objective Assessment of Outcome.
AB - OBJECTIVES: To investigate sleep and its predictors in preschoolers with mild
traumatic brain injury (mTBI). PARTICIPANTS AND PROCEDURE: The sample included
225 children, aged 18 to 60 months, divided into 3 groups: children with
accidental mTBI (n = 85), children with orthopedic injury (n = 58), and typically
developing children (n = 82). Retrospective reports of preinjury sleep and family
functioning were obtained as part of a baseline assessment at the time of
recruitment. Parental ratings of sleep problems were collected 6 months
postinjury on the full sample, and actigraphy data were collected on a subset of
children. Demographic, preinjury, and periinjury factors were examined as
potential predictors of sleep outcomes. RESULTS: No group differences were found
in ratings of sleep problems or for nighttime sleep duration and sleep
efficiency, as measured by actigraphy. Besides, preexisting sleep disturbances
and brain injury resulting in alteration of consciousness were identified as
predictors of poorer sleep in the mTBI group. CONCLUSION: Although mTBI did not
result in group-level sleep disturbances 6 months postinjury, the findings
suggest that premorbid and injury-related factors place some children at risk for
poorer sleep after mTBI. These factors should be documented so clinicians can
intervene early.
PMID- 28422897
TI - Outcomes Associated With Blast Versus Nonblast-Related Traumatic Brain Injury in
US Military Service Members and Veterans: A Systematic Review.
AB - OBJECTIVES: To systematically review the literature on comparative clinical and
functional outcomes following blast-related versus nonblast-related traumatic
brain injury (TBI) among US service members and Veterans. DESIGN: MEDLINE search
(January 2001 to June 2016) supplemented with hand search of reference lists and
input from peer reviewers. RESULTS: Thirty-one studies (in 33 articles) reported
on health outcomes; only 2 were rated low risk of bias. There was variation in
outcomes reported and methods of assessment. Blast and nonblast TBI groups had
similar rates of depression, sleep disorders, alcohol misuse, vision loss,
vestibular dysfunction, and functional status. Comparative outcomes were
inconsistent with regard to posttraumatic stress disorder diagnosis or symptoms,
headache, hearing loss, and neurocognitive function. Mortality, burn, limb loss,
and quality of life were each reported in few studies, most with small sample
sizes. Only 4 studies reported outcomes by blast injury mechanism. CONCLUSIONS:
Most clinical and functional outcomes appeared comparable in military service
members and Veterans with TBI, regardless of blast exposure. Inconsistent
findings and limited outcomes reporting indicate that more research is needed to
determine whether there is a distinct pattern of impairments and comorbidities
associated with blast-related TBI.
PMID- 28422898
TI - Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain
Injury Model Systems Study.
AB - OBJECTIVES: To characterize Internet and social media use among adults with
moderate to severe traumatic brain injury (TBI) and to compare demographic and
socioeconomic factors associated with Internet use between those with and without
TBI. SETTING: Ten Traumatic Brain Injury Model Systems centers. PARTICIPANTS:
Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems
National Database and eligible for follow-up from April 1, 2014, to March 31,
2015. DESIGN: Prospective cross-sectional observational cohort study. MAIN
MEASURES: Internet usage survey. RESULTS: The proportion of Internet users with
TBI was high (74%) but significantly lower than those in the general population
(84%). Smartphones were the most prevalent means of Internet access for persons
with TBI. The majority of Internet users with TBI had a profile account on a
social networking site (79%), with more than half of the sample reporting
multiplatform use of 2 or more social networking sites. CONCLUSION: Despite the
prevalence of Internet use among persons with TBI, technological disparities
remain in comparison with the general population. The extent of social media use
among persons with TBI demonstrates the potential of these platforms for social
engagement and other purposes. However, further research examining the quality of
online activities and identifying potential risk factors of problematic use is
recommended.
PMID- 28422899
TI - Variation in Adult Traumatic Brain Injury Outcomes in the United States.
AB - OBJECTIVE: To ascertain the degree of variation, by state of acute care
hospitalization, in outcomes associated with traumatic brain injury (TBI) in an
adult population. SETTING: All acute care hospitals in 21 states in the United
States in the year 2010. PARTICIPANTS: Adult (> 18 years) patients (N = 95 546)
admitted to a hospital with a moderate or severe TBI. DESIGN: Retrospective
cohort study using data from State Inpatient Databases from Agency for Healthcare
Research and Quality's Healthcare Cost and Utilization Project. MAIN MEASURES:
Inpatient mortality and discharge to inpatient rehabilitation. RESULTS: The
adjusted risk of inpatient mortality varied between states by as much as 40%,
with age, severity of injury, and insurance status as significant factors in both
outcomes. The adjusted risk of discharge to inpatient rehabilitation varied
between by more than 100% among the states measured. CONCLUSIONS: There was
clinically significant variation between states in inpatient mortality and
rehabilitation discharge after adjusting for variables known to affect each
outcome. Future efforts should be focused on identifying the causes of this state
to-state variation, how these causes affect patient outcomes, and may serve as a
guide to further standardization of treatment for traumatic brain injury across
the United States.
PMID- 28422900
TI - The Association Between Posttraumatic Stress Disorder and Perceptions of
Deployment-Related Injury in Veterans With and Without Mild Traumatic Brain
Injury.
AB - OBJECTIVES: To examine whether the association between posttraumatic stress
disorder (PTSD) and injury perceptions (ie, consequences, emotional
representations, and coherence) differs for Veterans with mild traumatic brain
injury (mTBI) compared with Veterans with non-TBI (ie, orthopedic). PARTICIPANTS:
Eighty Veterans injured during post-9/11 deployments. DESIGN: Observational, 2*2
factorial design. MAIN MEASURES: Injury histories ascertained using the Ohio
State University TBI-Identification Method and Deployment Injury Questionnaire;
Injury Perception Questionnaire-Revised (injury perceptions); Structured Clinical
Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition (PTSD diagnosis); and PTSD Symptom Checklist-Civilian Version (PTSD
symptoms). RESULTS: The association between PTSD diagnosis and injury perceptions
did not differ between Veterans with mTBI and those with non-TBIs, adjusting for
age, subjective pain, and depressive symptoms. PTSD symptom severity was
significantly associated with injury consequences (P < .0001) and emotional
representations (P < .0001), irrespective of injury type (mTBI vs non-TBI). Only
injury coherence was associated with a significant interaction between PTSD
symptom severity and mTBI (P = .04). CONCLUSION: PTSD symptom severity influences
perceptions about mTBI and non-TBIs sustained during deployment. Altering injury
perceptions may be an important treatment target for Veterans with co-occurring
PTSD and deployment-related injuries.
PMID- 28422901
TI - The Deployment Trauma Phenotype and Employment Status in Veterans of the Wars in
Iraq and Afghanistan.
AB - OBJECTIVES: To determine the prevalence of comorbid mild traumatic brain injury
(mTBI), posttraumatic stress disorder (PTSD), and depression, termed the
deployment trauma phenotype (DTP), and its constituent diagnoses' impact on
unemployment status in a national cohort of veterans. SETTING: Retrospective
analysis of the comprehensive TBI evaluation, a Veterans Affairs-wide protocol
for assessing TBI, employment status, and psychiatric impressions. PARTICIPANTS:
The final data set consisted of 48 821 veterans. MAIN OUTCOMES AND MEASURES:
Frequency of mTBI, PTSD, and depression in isolation and combinations and their
association with unemployment status. RESULTS: Age- and education-adjusted risk
ratios (RRs) showed that the mTBI-only group was the least likely to be
unemployed, RR = 0.65 (0.59-0.71). By contrast, the greatest likelihood of
unemployment was associated with membership in the DTP group, RR = 1.45 (1.36
1.56), and the comorbid PTSD and depression group, RR = 1.39 (1.27-1.52).
Furthermore, the DTP was nearly 3 times more prevalent (16.4%) in this sample
compared with comorbid PTSD and depression (5.7%), indicating that the DTP
conveys risk for unemployment to a significantly greater number of individuals.
CONCLUSIONS AND RELEVANCE: The comorbid and interactive conditions of PTSD,
depression, and mTBI, rather than mTBI in isolation, were linked to significant
risk for unemployment in this veteran cohort. These findings suggest that
multifaceted assessments and interventions to improve postdeployment
reintegration are needed.
PMID- 28422903
TI - Pirates and Predators.
PMID- 28422902
TI - Evaluation of the Osteoinductive Effect of PDGF-BB Associated With Different
Carriers in Bone Regeneration in Bone Surgical Defects in Rats.
AB - PURPOSE: Extensive bone defects in maxillofacial region can be corrected with
autograft. However the disadvantages of this type of therapy lead to the search
for new bone substitutes. Thus, we evaluated the biological behavior and
osteoinductive platelet-derived growth factor type BB (PDGF-BB) associated with
different carriers, by histological analysis and immunohistochemical histometric
critical defects performed in rat calvaria. MATERIALS AND METHODS: Critical
defects were created with 5-mm diameter calvaria of rats. Each defect was
randomly divided into 8 experimental groups, evaluated at 15 and 30 postoperative
days for histomorphometry and immunohistochemistry. RESULTS: The results showed
new bone formation in all groups, independent of postoperative time. At 30 days,
the beta-tricalcium phosphate matrix (TCP) group just did not differ from bone
matrix mineralized bovine (BIO) group in the new bone formation (P = 0.1403). In
none of the groups' analyzed biomaterials, growth factor stimulated increase in
bone formation (P > 0.05). CONCLUSION: With the methodology used, the growth
factor associated with the tested biomaterials did not induce new bone formation.
PMID- 28422904
TI - A comparison of prognosis calculators for geriatric trauma: A Prognostic
Assessment of Life and Limitations After Trauma in the Elderly consortium study.
AB - BACKGROUND: The nine-center Prognostic Assessment of Life and Limitations After
Trauma in the Elderly consortium has validated the Geriatric Trauma Outcome Score
(GTOS) as a prognosis calculator for injured elders. We compared GTOS'
performance to that of the Trauma Injury Severity Score (TRISS) in a multicenter
sample. METHODS: Three Prognostic Assessment of Life and Limitations After Trauma
in the Elderly centers not submitting subjects to the GTOS validation study
identified subjects aged 65 years to 102 years admitted from 2000 to 2013. GTOS
was specified using the formula [GTOS = age + (Injury Severity Score [ISS] * 2.5)
+ 22 (if transfused packed red cells (PRC) at 24 hours)]. TRISS uses the Revised
Trauma Score (RTS), dichotomizes age (<55 years = 0 and >=55 years = 1), and was
specified using the updated 1995 beta coefficients. TRISS Penetrating was
specified as [TRISSP = -2.5355 + (0.9934 * RTS) + (-0.0651 * ISS) + (-1.1360 *
Age)]. TRISS Blunt was specified as [TRISSB = -0.4499 + (0.8085 * RTS Total) + (
0.0835 * ISS) + (-1.7430 * Age)]. Each then became the sole predictor in a
separate logistic regression model to estimate probability of mortality. Model
performances were evaluated using misclassification rate, Brier score, and area
under the curve. RESULTS: Demographics (mean + SD) of subjects with complete data
(N = 10,894) were age, 78.3 years +/- 8.1 years; ISS, 10.9 +/- 8.4; RTS = 7.5 +/-
1.1; mortality = 6.9%; blunt mechanism = 98.6%; 3.1 % of subjects received PRCs.
The penetrating trauma subsample (n = 150) had a higher mortality rate of 20.0%.
The misclassification rates for the models were GTOS, 0.065; TRISSB, 0.051; and
TRISSP, 0.120. Brier scores were GTOS, 0.052; TRISSB, 0.041; and TRISSP, 0.084.
The area under the curves were GTOS, 0.844; TRISSB, 0.889; and TRISSP, 0.897.
CONCLUSION: GTOS and TRISS function similarly and accurately in predicting
probability of death for injured elders. GTOS has the advantages of a single
formula, fewer variables, and no reliance on data collected in the emergency room
or by other observers. LEVEL OF EVIDENCE: Prognostic, level II.
PMID- 28422905
TI - Distance matters: Effect of geographic trauma system resource organization on
fatal motor vehicle collisions.
AB - BACKGROUND: Trauma systems improve outcome; however, it is unclear how geographic
organization of trauma system resources (TSR) affects outcome. Our objective was
to evaluate the relationship of fatal motor vehicle collision (MVC) rates and the
distance from individual MVC locations to the nearest TSR as a measure of the
geographical organization of trauma systems, as well as how theoretical changes
in the distribution of TSR may affect fatal MVC rates. METHODS: All fatal MVC in
Pennsylvania 2013-2014 were mapped from the Fatality Analysis Reporting System
database. Deaths on scene were excluded. TSR including trauma centers and
helicopter bases were mapped. Distance between each fatal MVC and nearest TSR was
calculated. The primary outcome was fatal MVC rate per 100 million vehicle miles
traveled (VMT). Empiric Bayes kriging and hot spot analysis were performed to
evaluate geographic patterns in fatal MVC rates. Association between fatal MVC
rate and distance to the nearest TSR was evaluated with linear regression.
Spatial lag regression evaluated this association while controlling for MVC and
county-level characteristics. RESULTS: We identified 886 fatalities from 863
fatal MVC. Median fatal MVC rate was 0.187 per 100 million VMT. Higher fatal MVC
rates and fatality hot spots occur in locations farther from TSR. The fatal MVC
rate increased 0.141 per 100 million VMT for every 10 miles farther from the
nearest TSR (p < 0.01). When controlling for confounders, the fatal MVC rate
increased by 0.089 per 100 million VMT for every 10 miles farther from the
nearest TSR (p < 0.01). If two helicopters stationed at trauma centers were
relocated into the highest fatality regions, our model predicts a 12.3% relative
reduction in the overall MVC fatality rate. CONCLUSIONS: Increasing distance to
the nearest TSR is associated with increasing fatal MVC rate. The geographic
organization of trauma systems may impact outcome, and geospatial analysis can
allow data-driven changes to potentially improve outcome. LEVEL OF EVIDENCE:
Prognostic/Epidemiologic, level III; Case management, level III.
PMID- 28422906
TI - Risk factors and costs associated with nationwide nonelective readmission after
trauma.
AB - BACKGROUND: Most prior studies of readmission after trauma have been limited to
single institutions, whereas multi-institutional studies have been limited to
single states and an inability to distinguish between elective and nonelective
readmissions. The purpose of this study was to identify the risk factors and
costs associated with nonelective readmission after trauma across the United
States. METHODS: The Nationwide Readmission Database was queried for all patients
with nonelective admissions in 2013 and 2014 with a primary diagnosis of trauma.
Univariate and multivariate logistic regression identified risk factors for 30
day nonelective same- and different-hospital readmission. The diagnosis groups on
readmission were evaluated, and the total cost of readmissions was calculated.
RESULTS: There were 1,180,144 patients admitted for trauma, the 30-day
readmission rate was 9.4%, and 26.4% of readmissions occurred at a different
hospital. The median readmission cost for patients readmitted to the same
hospital was $8,298 (interquartile range, $4,899-$14,911), whereas the median
readmission cost for patients readmitted to a different hospital was $8,568
(interquartile range, $4,935-$16,078; p < 0.01). Multivariate regression revealed
that patients discharged against medical advice were at increased risk of
readmission (odds ratio, 2.79; p < 0.01) and readmission to a different facility
(odds ratio, 1.58; p < 0.01). Home health care was associated with a decreased
risk of readmission to a different hospital (odds ratio, 0.74; p < 0.01).
Septicemia and disseminated infections were the most common diagnoses on
readmission (8.4%) and readmission to a different hospital (8.6%). CONCLUSIONS: A
significant portion of US readmissions occur at different hospitals with
implications for continuity of care, quality metrics, cost, and resource
allocation. Home health care reduces the likelihood of nonelective readmission to
a different hospital. Infection was the most common reason for readmission, with
ramifications for outcomes research and quality improvement. LEVEL OF EVIDENCE:
Care management/epidimeological, level IV.
PMID- 28422907
TI - Adequacy and accuracy of nontrauma center computed tomography: What are we
missing?
AB - BACKGROUND: Timely and appropriate use of computed tomography (CT) scans is
critical to the evaluation of traumatic injuries. The objective of this study was
to assess the adequacy of CT scans performed at nontrauma centers (NTCs) as they
pertain to the management of trauma patients. METHODS: Adult patients transferred
to our ACS-verified Level I trauma center from any NTC between May and December
2012 were enrolled prospectively. Available CT images from NTCs were reviewed in
a blinded fashion by our facility's trauma radiologist; his interpretations were
compared with those from the NTC. Interpretations of the trauma centers (TCs)
images were compared with the NTC interpretations. Means and proportions were
used to summarize the data. RESULTS: A total of 235 consecutive patients with a
complete dataset were included, of which, 203 (86.4%) had a CT scan performed at
an NTC. Additional imaging was obtained at the TC in 76% of patients with outside
CT (154 of 203), with inadequacy of outside CTs for patient workup based on
mechanism of injury (76%) and technical inadequacy of outside images (31%) being
the main, nonexclusive reasons to repeat imaging. Image interpretation by the
trauma radiologist at the TC using NTC images identified missed injuries in 49%
of the patients, and 90% of these missed injuries were deemed clinically
significant, meaning the injury would have altered patient care had they been
identified. When the same body region was imaged at the TC, 54% had missed
injuries, of which 76% were deemed significant. CONCLUSION: This study
demonstrates inaccuracy in the interpretation of NTC images, which can lead to
inappropriate management of trauma patients. Parameters other than imaging need
to be used to identify patients requiring a higher level of care. LEVEL OF
EVIDENCE: Therapeutic and care management study, level V.
PMID- 28422908
TI - The Emergency Surgery Score (ESS) accurately predicts the occurrence of
postoperative complications in emergency surgery patients.
AB - BACKGROUND: The Emergency Surgery Score (ESS) was recently validated as a scoring
system to predict mortality in emergency surgery (ES) patients. We sought to
examine the ability of ESS to predict the occurrence of 30-day postoperative
complications in ES. METHODS: The 2011-2012 American College of Surgeons National
Surgical Quality Improvement Program (ACS-NSQIP) database was screened for all
surgical operations classified as "emergent." Thirty-day postoperative
complications were defined as per ACS-NSQIP (e.g., surgical site infection,
respiratory failure, acute renal failure). Each patient-related ESS was
calculated, and the correlation between ESS and the probability of occurrence of
30-day postoperative complications was assessed by calculating the c-statistic.
Univariate and multivariable models were also created to identify which ESS
components independently predict complications. RESULTS: Of 37,999 cases that
captured all ESS variables, 14,446 (38%) resulted in at least one 30-day
complication. The observed probability of a 30-day complication gradually
increased from 7% to 53% to 91% at scores of 0, 7, and 15, respectively, with a c
statistic of 0.78. For ESS >15, the complication rate plateaued at a mean of 92%.
On multivariable analyses, each of the 22 ESS components independently predicted
the occurrence of postoperative complications. CONCLUSIONS: ESS reliably predicts
postoperative complications in ES patients. Such a score could prove useful for
(1) perioperative patient and family counseling and (2) benchmarking the quality
of ES care. LEVEL OF EVIDENCE: Prognostic, level III.
PMID- 28422909
TI - Multi-institutional, prospective, observational study comparing the Gastrografin
challenge versus standard treatment in adhesive small bowel obstruction.
AB - INTRODUCTION: Existing trials studying the use of Gastrografin for management of
adhesive small bowel obstruction (SBO) are limited by methodological flaws and
small sample sizes. We compared institutional protocols with and without
Gastrografin (GG), hypothesizing that a SBO management protocol utilizing GG is
associated with lesser rates of exploration, shorter length of stay, and fewer
complications. METHODS: A multi-institutional, prospective, observational study
was performed on patients appropriate for GG with adhesive SBO. Exclusion
criteria were internal/external hernia, signs of strangulation, history of
abdominal/pelvic malignancy, or exploration within the past 6 weeks. Patients
receiving GG were compared to patients receiving standard care without GG.
RESULTS: Overall, 316 patients were included (58 +/- 18 years; 53% male). There
were 173 (55%) patients in the GG group (of whom 118 [75%] successfully passed)
and 143 patients in the non-GG group. There were no differences in duration of
obstipation (1.6 vs. 1.9 days, p = 0.77) or small bowel feces sign (32.9% vs.
25.0%, p = 0.14). Fewer patients in the GG protocol cohort had mesenteric edema
on CT (16.3% vs. 29.9%; p = 0.009). There was a lower rate of bowel resection
(6.9% vs. 21.0%, p < 0.001) and exploration rate in the GG group (20.8% vs.
44.1%, p < 0.0001). GG patients had a shorter duration of hospital stay (4 IQR 2
7 vs. 5 days IQR 2-12; p = 0.036) and a similar rate of complications (12.5% vs.
17.9%; p = 0.20). Multivariable analysis revealed that GG was independently
associated with successful nonoperative management. CONCLUSION: Patients
receiving Gastrografin for adhesive SBO had lower rates of exploration and
shorter hospital length of stay compared to patients who did not receive GG.
Adequately powered and well-designed randomized trials are required to confirm
these findings and establish causality. LEVEL OF EVIDENCE: Therapeutic, level
III.
PMID- 28422911
TI - Do vented chest seals differ in efficacy? An experimental evaluation using a
swine hemopneumothorax model.
AB - OBJECTIVE: Airways compromise was the second leading cause of potentially
preventable death among combat casualties. We investigated the ability of five
Food and Drug Administration-approved nonocclusive chest seals (CSs) to seal a
bleeding chest wound and prevent tension hemopneumothorax (HPTX) in a swine
model. METHODS: Following instrumentation, an open chest wound was created in the
left thorax of spontaneously air-breathing anesthetized pigs (n = 26; 43 kg).
Autologous fresh blood (226 mL) was then infused into the pleural cavity to
produce HPTX. The chest wounds were then sealed with CSs. The sealant strength
and venting function of CSs were challenged by infusion of 50 mL more blood
directly into the chest wound and incremental air injections into the pleural
cavity. Tension HPTX was defined as intrapleural (IP) pressure equal to or more
than +1 mm Hg and more than 20% deviation in physiologic measurements. RESULTS:
An open chest wound with HPTX raised IP pressure (~ -0.7 mm Hg) and caused
labored breathing and reductions in PaO2 and SvO2 (p < 0.01). Sealing the wounds
with the CSs restored IP pressure, and improved breathing and oxygenation.
Subsequent blood infusion into the wound and IP air injections produced CS
dependent responses. Chest seals with one-way valves (Bolin and SAM) did not
evacuate the blood efficiently; pooled blood either detached the CSs from skin
and leaked out (75%), or clotted and clogged the valve and led to tension HPTX
(25%). Conversely, CSs with laminar venting channels allowed escape of blood and
air from the pleural cavity and maintained IP pressure and oxygenation near
normal levels. Success rates were 100% for Sentinel and Russell (6/6); 67% for
HyFin (4/6); 25% for SAM (1/4); and 0% for Bolin (0/4) CSs (p = 0.002).
CONCLUSION: The sealant and valve function of vented CS differed widely in the
presence of bleeding chest wounds. Medics should be equipped with more effective
CSs for treating HPTX in the field.
PMID- 28422913
TI - Confessions of a Dinosaur.
PMID- 28422912
TI - Vascular complications from resuscitative endovascular balloon occlusion of the
aorta: Life over limb?
AB - BACKGROUND: Vascular complications from resuscitative endovascular balloon
occlusion of the aorta (REBOA) have been reported in as high as 13% with some
patients requiring lower-extremity amputation. We sought to review our
institution series of REBOA and assess our vascular complications. METHODS:
Retrospective review of all patients undergoing REBOA from October 2011 through
July 2016. Data were gathered from the Memorial Hermann Trauma Registry and the
hospital electronic medical records. Operative details and vascular injuries from
arterial access for REBOA insertion were recorded. RESULTS: Forty-eight patients
underwent REBOA during our study period. Thirty-eight had the 14 Fr. system
placed and 10 had the 7 Fr. system placed. Of the 24 surviving the removal of the
14 Fr. sheath, 19 had primary repair of the arteriotomy without vascular
complication. The other five required additional vascular procedures to repair
arteriotomy with no lower-extremity amputations. There were no vascular
complications of sheath removal with the 7 Fr. system, with no amputations.
CONCLUSION: Implementation of REBOA can be done safely without increased risk of
vascular access complications or limb loss. The 14 Fr. system will more likely
require further vascular procedures to address the access site, whereas the 7 Fr.
system will not. LEVEL OF EVIDENCE: Therapeutic/care management, level II.
PMID- 28422914
TI - Delays to the operating room increase mortality in sick trauma patients.
PMID- 28422915
TI - Enteral tranexamic acid attenuates vasopressor resistance and changes in alpha1
adrenergic receptor expression in hemorrhagic shock.
AB - BACKGROUND: Irreversible hemorrhagic shock is characterized by hyporesponsiveness
to vasopressor and fluid therapy. Little is known, however, about the mechanisms
that contribute to this phenomenon. Previous studies have shown that decreased
intestinal perfusion in hemorrhagic shock leads to proteolytically mediated
increases in gut permeability, with subsequent egress of vasoactive substances
systemically. Maintenance of blood pressure is achieved in part by alpha1
receptor modulation, which may be affected by vasoactive factors; we thus
hypothesized that decreases in hemodynamic stability and vasopressor response in
shock can be prevented by enteral protease inhibition. METHODS: Rats were exposed
to experimental hemorrhagic shock (35 mm Hg mean arterial blood pressure for 2
hours, followed by reperfusion for 2 hours) and challenged with phenylephrine (2
MUg/kg) at discrete intervals to measure vasopressor responsiveness. A second
group of animals received enteral injections with the protease inhibitor
tranexamic acid (TXA) (127 mM) along the small intestine and cecum 1 hour after
induction of hemorrhagic shock. RESULTS: Blood pressure response (duration and
amplitude) to phenylephrine after reperfusion was significantly attenuated in
animals subjected to hemorrhagic shock compared with baseline and control
nonshocked animals and was restored to near baseline by enteral TXA. Arteries
from shocked animals also displayed decreased alpha1 receptor density with
restoration to baseline after enteral TXA treatment. In vitro, rat shock plasma
decreased alpha1 receptor density in smooth muscle cells, which was also
abrogated by enteral TXA treatment. CONCLUSION: Results from this study
demonstrate that experimental hemorrhagic shock leads to decreased response to
the alpha1-selective agonist phenylephrine and decreased alpha1 receptor density
via circulating shock factors. These changes are mitigated by enteral TXA with
correspondingly improved hemodynamics. Proteolytic inhibition in the lumen of the
small intestine improves hemodynamics in hemorrhagic shock, possibly by restoring
alpha1 adrenergic functionality necessary to maintain systemic blood pressure and
perfusion.
PMID- 28422916
TI - Beware of the interval cholecystectomy.
AB - BACKGROUND: Despite limited data regarding the indications and effectiveness of
percutaneous cholecystostomy (PC) in the treatment of acute cholecystitis (AC),
usage has increased by over 500% since 1994. Many of these patients subsequently
undergo interval cholecystectomy (IC), a procedure that has not been rigorously
evaluated. This aim of this study was to quantify the morbidity and mortality
associated with the IC. METHODS: We included all consecutive adult patients (>18
years old) who underwent PC and IC from January 2008 to December 2013. Conversion
rate, length of operation, biliary injury, estimated blood loss, surgical site
infection, length of stay, and mortality were compared with 227 patients who
underwent cholecystectomy for AC during the same time interval. RESULTS: Of
18,501 patients who underwent cholecystectomy, 337 had at least one PC and 177
underwent subsequent IC. Compared with patients undergoing cholecystectomy for
clinically diagnosed AC, patients undergoing IC were older (69.8 vs. 54.9 years;
p < 0.001), thinner (body mass index, 28.7 vs. 31.1; p = 0.002), more complex by
Tokyo grade (1.9 vs. 1.1; p < 0.001), and American Society of Anesthesia
classification (3.0 vs. 2.5; p < 0.001), had longer operative times (120.7 vs.
92.5 minutes; p < 0.0001), more blood loss (30 vs. 15 mL; p = 0.01), and
increased rates of conversion (26.6% vs. 12.8%; p < 0.001), surgical site
infection (12.4% vs. 0.4%; p < 0.001), bowel injury (6.2% vs. 0.4%; p < 0.001),
and 1-year mortality (15.3% vs. 0.4%; p < 0.01). Nonsignificant trends included
significant biliary tract injury (3 vs. 0; p = 0.08) and longer length of stay
(7.3 vs. 4.8 days; p = 0.39). Linear regression identified body mass index (p =
0.03), time from admission to PC (p = 0.03), and American Society of Anesthesia
classification (p = 0.06) as predictors of a difficult IC. CONCLUSION: PC has
been widely adopted with limited description of the subsequent IC. Our data
detail the factors predicting the challenges of IC and document that it is a
difficult operation associated with significant morbidity. LEVEL OF EVIDENCE:
Therapeutic, level IV.
PMID- 28422918
TI - Reassessing the cardiac box: A comprehensive evaluation of the relationship
between thoracic gunshot wounds and cardiac injury.
AB - BACKGROUND: High-energy missiles can cause cardiac injury regardless of entrance
site. This study assesses the adequacy of the anatomic borders of the current
"cardiac box" to predict cardiac injury. METHODS: Retrospective autopsy review
was performed to identify patients with penetrating torso gunshot wounds (GSWs)
2011 to 2013. Using a circumferential grid system around the thorax, logistic
regression analysis was performed to detect differences in rates of cardiac
injury from entrance/exit wounds in the "cardiac box" versus the same for
entrance/exit wounds outside the box. Analysis was repeated to identify regions
to compare risk of cardiac injury between the current cardiac box and other
regions of the thorax. RESULTS: Over the study period, 263 patients (89% men;
mean age, 34 years; median injuries/person, 2) sustained 735 wounds (80% GSWs),
and 239 patients with 620 GSWs were identified for study. Of these, 95 (34%)
injured the heart. Of the 257 GSWs entering the cardiac box, 31% caused cardiac
injury, whereas 21% GSWs outside the cardiac box (n = 67) penetrated the heart,
suggesting that the current "cardiac box" is a poor predictor of cardiac injury
relative to the thoracic non-"cardiac box" regions (relative risk [RR], 0.96; p =
0.82). The regions from the anterior to posterior midline of the left thorax
provided the highest positive predictive value (41%) with high sensitivity (90%)
while minimizing false-positives, making this region the most statistically
significant discriminator of cardiac injury (RR, 2.9; p = 0.01). CONCLUSION: For
GSWs, the current cardiac box is inadequate to discriminate whether a GSW will
cause a cardiac injury. As expected, entrance wounds nearest to the heart are the
most likely to result in cardiac injury, but, from a clinical standpoint, it is
best to think outside the "box" for GSWs to the thorax. LEVEL OF EVIDENCE:
Therapeutic/care management, level IV.
PMID- 28422920
TI - A multiyear assessment of a hospital-school program to promote teen motor vehicle
safety.
AB - BACKGROUND: Motor vehicle crashes are the leading cause of death among teen
drivers. The main goal of this program was to reduce texting while driving among
high school teens through a unique peer-generated anti-texting campaign. METHODS:
The program consisted of two phases. In phase 1, student leaders participated in
a half-day, hospital-based experiential program that emphasized safe teen
driving. In phase 2, these students conceptualized and implemented an anti
texting while driving campaign during the school year. The program enrolled 32
schools with 137 student participants in phase 1.This study uses a prospective
quasi-experimental pre-post design. A presurvey and a follow-up online survey
were used. Response rate was 81%. In phase 2, two rounds of observations of
drivers were made near the participating schools at the beginning and end of the
phase 2 campaign. The results were analyzed using proportion tests. RESULTS:
There was a strong belief (6.49 on a seven-point scale) that texting while
driving could result in a crash. About 58% had texted while driving in the
previous 7 days in the pre-survey. This proportion decreased significantly to 44%
in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing
laws and feeling of empowerment to take action with a teen driver who was texting
improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens)
were observed in the first round, and 13,153 were observed in the second round of
observations. Significant reduction in the proportion of drivers texting while
driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver
observations support the effectiveness of this program in meeting the key
objective of reducing texting while driving. The program also influenced
teenagers' willingness to take positive steps when faced with a driver who was
texting. Future efforts should aim to influence social and peer norms. LEVEL OF
EVIDENCE: Therapeutic study, level III.
PMID- 28422921
TI - Population-based estimate of trauma-related deaths for law enforcement personnel:
Risks for death are higher and increasing over time.
AB - BACKGROUND: Trauma-related deaths remain an important public health problem. One
group susceptible to death due to traumatic mechanisms is US law enforcement
(LE). We hypothesized that LE officers experienced a higher chance of violent
death compared with the general US population and that risks have increased over
time. METHODS: The National Institute on Occupational Safety and Health National
Occupational Mortality Surveillance is a population-based survey of occupational
deaths. It includes data for workers who died during 1985 to 1998 in one of 30 US
states (EARLY period). Additional deaths were added from 23 US states in 1999,
2003 to 2004, 2007 to 2010 (LATE period). Mortality rates are estimated by
calculating proportionate mortality ratios (PMR). A PMR above 100 is considered
to exceed the average background risk for all occupations. All adults older than
18 years whose primary occupation was listed as "law enforcement worker" were
included in the analysis. RESULTS: Law enforcement personnel were more likely to
die from an injury compared with the general population (Fig. 1). The overall PMR
for injury in EARLY was 111 (95% confidence interval [CI], 108-114; p < 0.01),
and for LATE was 118 (95% CI, 110-127; p < 0.01). Four mechanisms of death
reached statistical significance: motor vehicle traffic (MVT)-driver, MVT-other,
intentional self-harm, and assault/homicide. The highest PMR in EARLY was
associated with firearms (PMR, 272; 95% CI, 207-350; p < 0.01). The highest PMR
in LATE was associated with death due to being a driver in an MVT (PMR, 194; 95%
CI, 169-222; p < 0.01). There were differences in risk of death by race and sex.
White females had the highest PMR due to assault and homicide (PMR, 317; 95% CI,
164-554; p < 0.01). All groups had similar risks of death due to intentional self
harm (PMR, 130-171). CONCLUSION: The risk of death for US LE officers is high and
increasing over time, suggesting an at-risk population that requires further
interventions. Targeted efforts based on risk factors, such as sex and race, may
assist with the development of prevention programs for this population. LEVEL OF
EVIDENCE: Epidemiologic study, level II.
PMID- 28422922
TI - The spatial epidemiology of pediatric trauma: A statewide assessment.
AB - BACKGROUND: Despite significant advances in the prevention and treatment of
pediatric trauma, preventable injuries continue to burden the lives of millions
of children. To target prevention strategies, it is critical to identify areas
with high burdens of pediatric trauma. Therefore, this study analyzed statewide
data from the Ohio Trauma Registry from 2007 to 2012 to identify geographical
patterns in pediatric injury. METHODS: Data from the first hospital of care for
16,330 pediatric trauma patients younger than 16 years were analyzed using the
disease mapping method adaptive spatial filtering to estimate a series of maps
that display age- and sex-adjusted rates of pediatric trauma, severe trauma, and
standardized mortality ratios while controlling for population size to create
stable estimates throughout the study area. The locations of all trauma centers
were mapped to highlight access to trauma care. RESULTS: Areas with significantly
higher than expected rates of severe injury were identified in nonurban areas,
where children lacked timely access to a pediatric trauma center or Level I adult
trauma center. Although highest standardized mortality ratios were in urban
areas, nonurban areas experienced elevated mortality with rates over four times
higher than expected. CONCLUSION: Areas with higher than expected age- and sex
adjusted rates of severe injury and mortality should be further explored to
identify opportunities for injury prevention and appropriate access to timely
care. LEVEL OF EVIDENCE: Epidemiologic study, level III.
PMID- 28422923
TI - A cross-sectional study of emergency care utilization and associated costs of
violent-related (assault) injuries in the United States.
AB - BACKGROUND: Violent-related (assault) injuries are a leading cause of death and
disability in the United States. Many violent injury victims seek treatment in
the emergency department (ED). Our objectives were to (1) estimate rates of
violent-related injuries evaluated in United States EDs, (2) estimate linear
trends in ED visits for violent-related injuries from 2000 to 2010, and (3) to
determine the associated health care and work-loss costs. METHODS: We examined
adults 18 years and older from a nationally representative survey (the National
Hospital Ambulatory Medical Care Survey) of ED visits, from 2000 to 2010. Violent
injury was defined using International Classification of Diseases-9th Rev.
Clinical Modification, diagnosis and mechanism of injury codes. We calculated
rates of ED visits for violent injuries. Medical and work-loss costs accrued by
these injuries were calculated for 2005, inflation-adjusted to 2011 dollars using
the WISQARS Cost of Injury Reports. RESULTS: An annual average of 1.4 million
adults were treated for violent injuries in EDs from 2000 to 2010, comprising
1.6% (95% confidence interval, 1.5%-1.6%) of all US adult ED visits. Young adults
(18-25 years), men, nonwhites, uninsured or publically insured patients, and
those residing in high poverty urban areas were at increased risk for ED visits
for violent injury. The 1-year, inflation-adjusted medical and work-loss cost of
violent-inflicted injuries in adults in the United States was US $49.5 billion.
CONCLUSION: Violent injuries account for over one million ED visits annually
among adults, with no change in rates over the past decade. Young black men are
at especially increased risk for ED visits for violent injuries. Overall, violent
related injuries resulted in substantial financial and societal costs. LEVEL OF
EVIDENCE: Epidemiological study, level III.
PMID- 28422924
TI - "Pay it Forward" Eastern Association for the Surgery of Trauma 2017 Presidential
Address.
PMID- 28422925
TI - Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients.
AB - BACKGROUND: Previous studies identified B cell gene signatures and predominance
of specific B cell subsets as a marker of operational tolerance after kidney
transplantation. These findings suggested a role for B cells in the establishment
or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of
whom achieved tolerance after combined kidney/bone marrow transplantation.
METHODS: Peripheral B cell subsets were examined longitudinally by flow
cytometry. Immunoglobulin heavy chain repertoire analysis was performed using
next-generation sequencing. Lastly, the patients' serum reactivity to HLA was
assessed by Luminex. RESULTS: B cell counts recovered approximately 1 year
posttransplant except for 1 subject who experienced delayed reconstitution. This
subject resumed immunosuppression for acute rejection at 10 months posttransplant
and underwent preemptive retransplantation at 3 years for chronic rejection. B
cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional
B cells and a diversified clonal repertoire. However, all 4 subjects showed
prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B
cell counts were still low and the clonal B cell repertoire very limited. The
predominance of memory B cells was also associated with high levels of
somatically mutated immunoglobulin heavy chain variable sequences and transient
serum reactivity to HLA. CONCLUSIONS: Our observations reveal the presence of
memory B cells early posttransplant that likely escaped the preparative regimen
at a time consistent with the establishment of tolerance. Further studies are
warranted to characterize the functional properties of these persisting memory
cells and evaluate their potential contribution to tolerance induction.
PMID- 28422926
TI - Targeting High Calcineurin Inhibitor Levels After Acute Rejection With Less
Tremor: A New Strategy.
PMID- 28422928
TI - Are Nurse Leaders Prepared to Lead Across the Continuum of Care in the New
Paradigm?
AB - The movement toward linking reimbursement with outcomes necessitates providing
care across a continuum of settings, leading to the need for a new healthcare
paradigm. Issues related to shifting to this new paradigm include disagreement
about what this paradigm encompasses, the fragmentation of the healthcare system,
and overreliance on the medical model as a framework for driving health policy
decisions. We advocate for nurse leaders to guide the development of this new
paradigm.
PMID- 28422927
TI - The Relationship Between Specialty Certification of Individual Nurses and
Outcomes: Developing a Standardized Taxonomy for Research.
AB - Specialty certification is an important method to demonstrate that RNs possess
advanced training, knowledge, and competencies required to provide safe, high
quality care for specific populations.
PMID- 28422929
TI - Examining the Educational Experiences and Outcomes of the American Organization
of Nurse Executives Nurse Manager Fellowship Program: A Multiclass Study.
PMID- 28422930
TI - Exploring the Best Practices of Nursing Research Councils in Magnet(r)
Organizations: Findings From a Qualitative Research Study.
AB - OBJECTIVE: The objective of this descriptive qualitative study was to identify
best practices of nursing research councils (NRCs) at Magnet(r)-designated
hospitals. BACKGROUND: Nursing research (NR) is essential, adding to the body of
nursing knowledge. Applying NR to the bedside improves care, enhances patient
safety, and is an imperative for nursing leaders. METHODS: We interviewed NR
designees at 26 Magnet-recognized hospitals about the structure and function of
their NRCs and used structural coding to identify best practices. RESULTS: Most
organizations link NR and evidence-based practice. Council membership includes
leadership and clinical nurses. Councils conduct scientific reviews for nursing
studies, supporting nurse principal investigators. Tracking and reporting of NR
vary widely and are challenging. Councils provide education, sponsor research
days, and collaborate interprofessionally, including with academic partners.
CONCLUSIONS: Findings from this study demonstrate the need to create formal
processes to track and report NR and to develop outcome-focused NR education.
PMID- 28422931
TI - Development and Psychometric Evaluation of the Professional Practice Work
Environment Inventory.
AB - OBJECTIVE: The purpose is to examine the psychometric properties of the
professional practice work environment inventory (PPWEI). BACKGROUND: Derived
from the Professional Practice Environment (PPE) and the Revised PPE scales, the
PPWEI was designed to measure 8 components of the PPE that can be used to assist
nurse administrators in decision-making. METHODS: A psychometric evaluation was
undertaken with 874 nurses who were providing direct care to patients at the
Massachusetts General Hospital and who provided no missing data on the newly
developed 72-item PPWEI. RESULTS: Cronbach's alpha internal consistency
reliability of the total score was .93, with 61 items having factor loadings more
than .50, the factor loading cutoff used to define the component subscales.
Principal component analyses with varimax rotation and Kaiser normalization
demonstrated 8 components, explaining 64.6% of variance. Cronbach's alpha
reliability coefficients of the PPWEI subscales ranged from .82 to .93.
CONCLUSION: The multidimensional PPWEI is a psychometrically sound measure of
several components of the PPE in the acute care setting and sufficiently reliable
and valid for use as independent subscales in healthcare research.
PMID- 28422932
TI - Clarifying the Conundrum: Evidence-Based Practice, Quality Improvement, or
Research?: The Clinical Scholarship Continuum.
AB - Nurses' active involvement in clinical scholarship is necessary to advance the
nursing profession and improve patient outcomes. Yet, definitional confusion and
numerous barriers exist to clinical scholarship in and across academic and
patient care settings. We discuss factors that pose barriers to the continuum of
clinical scholarship and suggest opportunities for clinician-researcher
collaborations that promote nurses' engagement in evidence-based practice,
quality improvement, and research.
PMID- 28422933
TI - Nursing Informatics Competency Assessment for the Nurse Leader: Instrument
Refinement, Validation, and Psychometric Analysis.
AB - OBJECTIVE: The aim of this article is to refine and validate a new instrument,
Nursing Informatics Competency Assessment for the Nurse Leader (NL). BACKGROUND:
Because health information technology rapidly advances, the NL requires greater
levels of informatics knowledge. METHODS: Item reduction and psychometric
analysis methodology RESULTS: A total of 357 national NLs completed the survey.
Exploratory factor analysis resulted in a final 6-factor solution that contained
26 items: (1) strategic implementation management, (2) advanced information
management and education, (3) executive planning, (4) ethical and legal concepts,
(5) information systems concepts, and (6) requirements and system selection.
Cronbach's alpha were .96, .91, .90, .83, .92, .81, respectively. CONCLUSION: We
established a valid and reliable nursing informatics competency assessment
instrument with sufficient specificity to guide NLs to recognize the competencies
required in their role, create solutions to address potential gaps, and enhance
delivery of patient care.
PMID- 28422934
TI - Impact of Professional Nursing Practices on Patient/Nurse Outcomes: Testing the
Essential Professional Nursing Practices Instrument.
AB - Increasing patient and healthcare system complexity and the need to accurately
measure the engagement of clinical nurses (CNs) in holistic, professional nursing
practice indicates that an update to the Essentials of Magnetism instrument is
needed. The purposes of this research were to critique and weight items, assess
the value and psychometric properties of the newly constructed Essential
Professional Nursing Practices (EPNP) instrument, and establish relationships
between EPNPs and CN job, practice, and nurse-assessed patient satisfaction.
PMID- 28422935
TI - The Baptist Health Nurse Retention Questionnaire: A Methodological Study, Part 1.
AB - OBJECTIVE: The purposes of this study were to develop and test the Baptist Health
Nurse Retention Questionnaire (BHNRQ) and examine the importance of nurse
retention factors. BACKGROUND: Multiple factors, including increasing patient
acuity levels, have led to concerns regarding nurse retention. An understanding
of current factors related to retention is limited. METHODS: To establish the
psychometric properties of the BHNRQ, data were collected from 279 bedside nurses
at a 391-bed, Magnet(r) redesignated community hospital. A principal component
analysis was conducted to determine the subscale structure of the BHNRQ.
Additional analyses were conducted related to content validity and test-retest
reliability. RESULTS: The results of the principal components analysis revealed 3
subscales: nursing practice, management, and staffing. Analyses demonstrate that
the BHNRQ is a reliable and valid instrument for measuring nurse retention
factors. CONCLUSION: The BHNRQ was found to be a clinically useful instrument for
measuring important factors related to nurse retention.
PMID- 28422936
TI - Phenotypic Characterization of Adherent Cells Population CD34+ CD90+ CD105+
Derived from Wharton's Jelly.
AB - BACKGROUND Mesenchymal stromal cells, MSCs, show expression of specific antigens
on their surface. The aim of the study is to assess the phenotype of stem cells
like isolated from the umbilical cord with respect to the presence of surface
antigens CD34, CD90, and CD105 and differences in the expression of surface
antigens in cells isolated from freshly sampled material in comparison with the
phenotype of cells from in vitro culture. MATERIAL AND METHODS Stem cells
collected from the umbilical cord from healthy patients and then cultured in
vitro. To assess the phenotype of stem cells, cytometric analysis was carried
out. To assess the phenotype of cells we used fluorescently labelled monoclonal
antibodies: APC Mouse anti-human CD34, PC5 Mouse anti-human CD90 and PE Mouse
anti-human CD105. RESULTS In the case of cells from the umbilical cord and then
cultured in vitro for the period of 10-14 days CD34 expression is lower (69,5%)
in comparison with the group of cells not cultured. Not cultured cells were
demonstrated 37% of cells co-expression of antigens CD34 and CD105, over 21% of
CD34/CD90 cells and over 24% of CD105/CD90. Cultured cells group was showed
higher percentage of CD90, CD105, CD34/CD105, CD34/CD90, CD105/CD90 in comparison
with not cultured cells. CONCLUSIONS Our reults suggested that adherent cells
population from umbilical cord, demonstrate CD34 expression In vivo. Moreover,
the phenotype of MSCs, mainly in the context of CD34 expression, may vary
depending on the place of collection of cells and the length of growing the cell
culture.
PMID- 28422937
TI - Let there be sight.
PMID- 28422938
TI - Corneal repair: a clear vision.
PMID- 28422939
TI - Predictive factors for achieving independent walking in children with Guillain
Barre syndrome.
AB - BackgroundTo determine the predictors of achieving independent walking at 2 and 6
months after onset of weakness in children with Guillain-Barre syndrome
(GBS).MethodsChildren with GBS admitted to the Tabriz Children's Hospital were
studied prospectively. All patients had frequent clinical evaluations until
achieving independent walking. Unaided walking at 2 and 6 months and factors
influencing these outcomes were determined using both univariate and multiple
analyses.ResultsBetween 2003 and 2014, 324 children (mean age: 5.3+/-3.66 years)
were admitted. The mean duration to independent walking was 2.97+/-3.02 months;
90.5% of patients could walk independently at 6 months. In the univariate
analysis, disability score of >3 (P=0.03), autonomic nerve involvement (P=0.003),
cranial nerve involvement (P=0.008), and absent compound muscle action potential
(CMAP; P=0.048) were found to be significantly associated with poor walking
outcome at 6 months. In the multivariate analysis, cranial nerve involvement
(P=0.008) and absence of CMAP (P=0.022) were independently associated with poor
functional outcome.ConclusionDisability score >3, cranial and autonomic nerve
involvement, and absence of CMAP were predictors of independent walking in
childhood GBS in this study; early rehabilitation program may prevent further
impairments secondary to immobility in these patients.
PMID- 28422940
TI - Body composition at birth and height at 2 years: a prospective cohort study among
children in Jimma, Ethiopia.
AB - BACKGROUNDLow birth weight is associated with childhood stunting, but equivalent
associations for birth body composition (BC) remain unknown. The aim of this
study was to assess associations between birth BC and height-for-age z-score
(HAZ) at 2 years of age.METHODSIn a prospective cohort study, fat mass (FM) and
fat-free mass (FFM) were measured using air-displacement plethysmography within
48 h of birth. Linear regression models were applied to study the relationship
between BC at birth and HAZ at 24 +/-3 months.RESULTSA total of 268 children with
height assessment at 2 years were included. Mean+/-SD HAZ at 2 years of age was
1.2+/-1.2, with 25.8% classified as stunted (HAZ <-2SD). FFM at birth was
positively associated with HAZ at 2 years, independent of length at birth. When
adjusted for potential confounders, HAZ at 2 years was 0.73 higher for each
additional kg FFM at birth (beta=0.73, 95% CI: 0.08, 1.38). FM was not associated
with HAZ at 2 years in any model.CONCLUSIONThe FFM component of birth weight,
independent of length at birth, explained variability in HAZ at 2 years. Further
studies are required to explore how changes in early infant BC are associated
with linear growth.
PMID- 28422941
TI - Metabolism-related microRNAs in maternal breast milk are influenced by premature
delivery.
AB - BackgroundMaternal breast milk (MBM) is enriched in microRNAs, factors that
regulate protein translation throughout the human body. MBM from mothers of term
and preterm infants differs in nutrient, hormone, and bioactive-factor
composition, but the microRNA differences between these groups have not been
compared. We hypothesized that gestational age at delivery influences microRNA in
MBM, particularly microRNAs involved in immunologic and metabolic
regulation.MethodsMBM from mothers of premature infants (pMBM) obtained 3-4 weeks
post delivery was compared with MBM from mothers of term infants obtained at
birth (tColostrum) and 3-4 weeks post delivery (tMBM). The microRNA profile in
lipid and skim fractions of each sample was evaluated with high-throughput
sequencing.ResultsThe expression profiles of nine microRNAs in lipid and skim
pMBM differed from those in tMBM. Gene targets of these microRNAs were
functionally related to elemental metabolism and lipid biosynthesis. The microRNA
profile of tColostrum was also distinct from that of pMBM, but it clustered
closely with tMBM. Twenty-one microRNAs correlated with gestational age
demonstrated limited relationships with method of delivery, but not other
maternal-infant factors.ConclusionPremature delivery results in a unique MBM
microRNA profile with metabolic targets. This suggests that preterm milk may have
adaptive functions for growth in premature infants.
PMID- 28422942
TI - Development of tandem mass spectrometry-based creatinine measurement using dried
blood spot for newborn mass screening.
AB - BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are the
most prevalent etiologies of pediatric chronic kidney disease (CKD). However, no
robust mass screening methods have been developed to detect patients with CAKUT,
making early intervention to prevent progressive renal failure
challenging.MethodsWe applied tandem mass spectrometry (MS/MS) to measure the
creatinine (Cr) value from dried blood spot (DBS) analysis, which has been used
for newborn mass screening. Subsequently, we evaluated the correlation between
DBS Cr measured by MS/MS and serum Cr measured by the conventional method in
pediatric patients with CKD. Finally, DBS Cr was measured in 190 full-term,
healthy newborns on days 4-6 after birth.ResultsWe established a system of MS/MS
based measurement of Cr from DBS. Measured DBS Cr in the pediatric patients
showed a strong association with serum Cr (r=0.86; P<0.01). The median DBS Cr
value in newborns was 0.222 (interquartile range: 0.189, 0.269) mg/dl. No
significant correlations were found between DBS Cr values and body weight, Apgar
score, gestational age, and sex in newborns.ConclusionWe successfully established
a method for MS/MS-based measurement of Cr for newborn screening and determined
normal reference values for full-term newborns.
PMID- 28422944
TI - Growth and development in late-preterm infants: what can public policy do?
PMID- 28422943
TI - The effect of prenatal TVOC exposure on birth and infantile weight: the Mothers
and Children's Environmental Health study.
AB - BACKGROUNDVolatile organic compounds (VOCs) might restrict prenatal and postnatal
growth. However, the effect of the exposure of prenatal VOCs on postnatal growth
has not been studied sufficiently. Thus, we investigated the relationship between
the exposure of total volatile organic compounds (TVOCs) during pregnancy and its
effects on postnatal growth.METHODSA total of 383 pregnant participants were
enrolled from 2006 to 2008. We investigated maternal characteristics using a
questionnaire. Personal air samples of TVOCs were obtained in mid or late
pregnancy. After these mothers had given birth, 360 singleton newborns were
selected and postnatal follow-up data were collected at 6, 12, 24, and 36 months,
as well as anthropometric factors including body weight. Multiple general linear
and mixed models were applied for statistical analyses.RESULTSThe mean
concentration of prenatal exposure to TVOCs was 284.2 MUg/m3 and that of
formaldehyde was 81.6 MUg/m3. The birth weight of newborns decreased
significantly with prenatal TVOC exposure (beta=-45.89, P=0.04). The adjusted
mean body weight was 300 g lower in the high-TVOC group (?75th) compared with
that in the low-exposure group (<75th).CONCLUSIONThese results indicate that
elevated exposure to TVOCs during the prenatal period may adversely influence
early postnatal growth.
PMID- 28422945
TI - Growth pattern and final height of very preterm vs. very low birth weight
infants.
AB - BackgroundBoth very preterm (VP; i.e., gestational age <32 weeks) and very low
birth weight (VLBW; i.e., birth weight <1,500 g) are used as inclusion criteria
by studies on preterm birth. We aimed to quantify the impact of these entities on
postnatal growth until final height.MethodsSubjects born VP and/or with VLBW from
the Project On Preterm and Small-for-gestational-age infants cohort were
classified as follows: (1) VP+/VLBW+ (n=495), (2) VP+/VLBW- (n=207), or (3) VP
/VLBW+ (n=296) infants. Anthropometric data were collected at birth, 3, 6, 12,
and 24 months' corrected age, and at 5 and 19 years. At 19 years, 590/998 (59%)
of the subjects enrolled in 1983 were followed up.ResultsBirth size was smallest
in the VP-/VLBW+ group compared with the VP+/VLBW+ and VP+/VLBW- groups. During
childhood, length, weight, and head circumference SD scores increased in the VP
/VLBW+ group, whereas SD scores in the VP+/VLBW+ and VP+/VLBW- groups either
remained stable or decreased. Despite catch-up growth, VP-/VLBW+ infants remained
the shortest and lightest at age 19.ConclusionClassification on the basis of VP
and VLBW impacts growth, causing different growth patterns for infants born
VP+/VLBW+, VP+/VLBW-, or VP-/VLBW+. For future studies, we recommend, at least
for industrialized countries, including preterm infants based on gestational age.
PMID- 28422946
TI - Pediatric Cushing disease: disparities in disease severity and outcomes in the
Hispanic and African-American populations.
AB - BackgroundLittle is known about the contribution of racial and socioeconomic
disparities to severity and outcomes in children with Cushing disease
(CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African
American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study.
A 10-point index for rating severity (CD severity) incorporated the degree of
hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements,
disease duration, and tumor characteristics. Race, ethnicity, age, gender, local
obesity prevalence, estimated median income, and access to care were assessed in
regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group
was worse than that in the non-HW group (4.9+/-2.0 vs. 4.1+/-1.9, P=0.023);
driving factors included higher cortisol levels and larger tumor size. Multiple
regression models confirmed that race (P=0.027) and older age (P=0.014) were the
most important predictors of worse CD severity. When followed up a median of 2.3
years after surgery, the relative risk for persistent CD combined with recurrence
was 2.8 times higher in the HI/AA group compared with that in the non-HW group
(95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving
forces for the discrepancy in severity of CD are older age and race/ethnicity.
Importantly, the risk for persistent and recurrent CD was higher in minority
children.
PMID- 28422947
TI - Factors affecting the cognitive profile of 11-year-old children born very
preterm.
AB - BackgroundPreterm birth is a risk for cognitive development. This study assessed
the cognitive profile of children born very preterm at the age of 11 years as
well as the associated risk factors.MethodsA total of 128 children born very
preterm were included. Magnetic resonance imaging was performed at term age.
Cognitive development was assessed using the full-scale intelligence quotient
(IQ) and four domains of the Wechsler Intelligence Scale for Children, fourth
edition (WISC-IV), Finnish translation. The results were compared with test
norms.ResultsMost study children performed at average (51%) or low average (21%)
levels in the full-scale IQ assessment. The correlation between 5- and 11-year
full-scale IQ was 0.73 (P<0.001). Compared with the normative data, children born
very preterm performed poorer in all domains of the cognitive profile. The only
significant risk factor for poor general cognition was major brain pathology.
When considering all four domains of WISC-IV, low paternal education, male
gender, and low birth weight z score were also found to be significant risk
factors.ConclusionsLess than one-third of the children born very preterm
performed below the low average cognitive level at 11 years of age. Specific
neonatal and sociodemographic risk factors were identified as affecting the
cognitive profile.
PMID- 28422948
TI - Beyond the uterine environment: a nonhuman primate model to investigate maternal
fetal and neonatal outcomes following chronic intrauterine infection.
AB - BackgroundIntrauterine infection is a significant cause of early preterm birth.
We have developed a fetal-neonatal model in the rhesus macaque to determine the
impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal
reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were
randomized to be inoculated with U. parvum (serovar 1; 105 c.f.u.) or control
media at ~120 days' gestational age (dGA). Neonates were delivered by elective
hysterotomy at 135-147 dGA (term=167d), stabilized, and cared for in our nonhuman
primate neonatal intensive care unit. Neonatal reflex behaviors were assessed
from birth, and fetal and postnatal brain magnetic resonance imaging (MRI) was
performed.ResultsA total of 13 preterm and 5 term macaque infants were included
in the study. Ten preterm infants survived to 6 months of age. U. parvum-infected
preterm neonates required more intensive respiratory support than did control
infants. MRI studies suggested a potential perturbation of brain growth and white
matter maturation with exposure to intra-amniotic infection.ConclusionWe have
demonstrated the feasibility of longitudinal fetal-neonatal studies in the
preterm rhesus macaque after chronic intrauterine infection. Future studies will
examine long-term neurobehavioral outcomes, cognitive development,
neuropathology, and in vivo brain imaging to determine the safety of antenatal
antibiotic treatment for intrauterine infection.
PMID- 28422949
TI - Heparin-binding EGF-like growth factor promotes neuronal nitric oxide synthase
expression and protects the enteric nervous system after necrotizing
enterocolitis.
AB - BackgroundNeonatal necrotizing enterocolitis (NEC) is associated with alterations
of the enteric nervous system (ENS), with loss of neuronal nitric oxide synthase
(nNOS)-expressing neurons in the intestine. The aim of this study was to
investigate the roles of heparin-binding EGF-like growth factor (HB-EGF) in
neural stem cell (NSC) differentiation, nNOS expression, and effects on ENS
integrity during experimental NEC.MethodsThe effects of HB-EGF on NSC
differentiation and nNOS production were determined using cultured enteric NSCs.
Myenteric neuronal subpopulations were examined in HB-EGF knockout mice. Rat pups
were exposed to experimental NEC, and the effects of HB-EGF treatment on nNOS
production and intestinal neuronal apoptosis were determined.ResultsHB-EGF
promotes NSC differentiation, with increased nNOS production in differentiated
neurons and glial cells. Moreover, loss of nNOS-expressing neurons in the
myenteric plexus and impaired neurite outgrowth were associated with absence of
the HB-EGF gene. In addition, administration of HB-EGF preserves nNOS expression
in the myenteric plexus and reduces enteric neuronal apoptosis during
experimental NEC.ConclusionHB-EGF promotes the differentiation of enteric NSCs
into neurons in a nitric oxide (NO)-dependent manner, and protects the ENS from
NEC-induced injury, providing new insights into potential therapeutic strategies
for the treatment of NEC in the future.
PMID- 28422950
TI - Application of high-resolution array comparative genomic hybridization in
children with unknown syndromic microcephaly.
AB - BackroundMicrocephaly can either be isolated or it may coexist with other
neurological entities and/or multiple congenital anomalies, known as syndromic
microcephaly. Although many syndromic cases can be classified based on the
characteristic phenotype, some others remain uncertain and require further
investigation. The present study describes the application of array-comparative
genomic hybridization (array-CGH) as a diagnostic tool for the study of patients
with clinically unknown syndromic microcephaly.MethodsFrom a cohort of 210
unrelated patients referred with syndromic microcephaly, we applied array-CGH
analysis in 53 undiagnosed cases. In all the 53 cases except one, previous
standard karyotype was negative. High-resolution 4 * 180K and 1 * 244K Agilent
arrays were used in this study.ResultsIn 25 out of the 53 patients with
microcephaly among other phenotypic anomalies, array-CGH revealed copy number
variations (CNVs) ranging in size between 15 kb and 31.6 Mb. The identified CNVs
were definitely causal for microcephaly in 11/53, probably causal in 7/53, and
not causal for microcephaly in 7/53 patients. Genes potentially contributing to
brain deficit were revealed in 16/53 patients.ConclusionsArray-CGH contributes to
the elucidation of undefined syndromic microcephalic cases by permitting the
discovery of novel microdeletions and/or microduplications. It also allows a more
precise genotype-phenotype correlation by the accurate definition of the
breakpoints in the deleted/duplicated regions.
PMID- 28422951
TI - Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in
Mexican schoolchildren.
AB - BackgroundThere is little information about the possible role of Helicobacter
pylori infection on appetite-regulating peptides in children. This study
evaluated the association between H. pylori infection and serum levels of
ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight
schoolchildren, students at boarding schools in Mexico City, participated. H.
pylori infection status was determined every 6 months for 1 year by a breath test
using 13C-urea; schoolchildren with consistently positive or negative results
were selected to participate. Age, sex, and body mass index (BMI) were recorded.
Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme
linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori
infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to
0.09), compared to the schoolchildren without infection, after adjustment by age,
gender, and BMI. And the children with the infection had a median of obestatin
lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected
children after adjustment by BMI.ConclusionAssociation was found between H.
pylori infection and decreased serum concentrations of leptin and obestatin.
These results suggest that in schoolchildren, H. pylori infection affects the
levels of hormones implicated in regulating appetite and energy homeostasis.
PMID- 28422952
TI - When cancer needs what's non-essential.
AB - The non-essential amino acids serine and glycine are critical for proliferative
metabolism. A study in Nature now finds that dietary serine and glycine
deprivation inhibits growth of some tumours. Whether this dietary intervention is
effective depends on both the oncogenic context and tumour tissue of origin.
PMID- 28422953
TI - Great spotted cuckoo nestlings have no antipredatory effect on magpie or carrion
crow host nests in southern Spain.
AB - Host defences against cuckoo parasitism and cuckoo trickeries to overcome them
are a classic example of antagonistic coevolution. Recently it has been reported
that this relationship may turn to be mutualistic in the case of the carrion crow
(Corvus corone) and its brood parasite, the great spotted cuckoo (Clamator
glandarius), given that experimentally and naturally parasitized nests were
depredated at a lower rate than non-parasitized nests. This result was
interpreted as a consequence of the antipredatory properties of a fetid cloacal
secretion produced by cuckoo nestlings, which presumably deters predators from
parasitized host nests. This potential defensive mechanism would therefore
explain the detected higher fledgling success of parasitized nests during
breeding seasons with high predation risk. Here, in a different study population,
we explored the expected benefits in terms of reduced nest predation in naturally
and experimentally parasitized nests of two different host species, carrion crows
and magpies (Pica pica). During the incubation phase non-parasitized nests were
depredated more frequently than parasitized nests. However, during the nestling
phase, parasitized nests were not depredated at a lower rate than non-parasitized
nests, neither in magpie nor in carrion crow nests, and experimental
translocation of great spotted cuckoo hatchlings did not reveal causal effects
between parasitism state and predation rate of host nests. Therefore, our results
do not fit expectations and, thus, do not support the fascinating possibility
that great spotted cuckoo nestlings could have an antipredatory effect for host
nestlings, at least in our study area. We also discuss different possibilities
that may conciliate these with previous results, but also several alternative
explanations, including the lack of generalizability of the previously documented
mutualistic association.
PMID- 28422954
TI - Identification of the contribution of contact and aerial biomechanical parameters
in acrobatic performance.
AB - INTRODUCTION: Teaching acrobatic skills with a minimal amount of repetition is a
major challenge for coaches. Biomechanical, statistical or computer simulation
tools can help them identify the most determinant factors of performance. Release
parameters, change in moment of inertia and segmental momentum transfers were
identified in the prediction of acrobatics success. The purpose of the present
study was to evaluate the relative contribution of these parameters in
performance throughout expertise or optimisation based improvements. The counter
movement forward in flight (CMFIF) was chosen for its intrinsic dichotomy between
the accessibility of its attempt and complexity of its mastery. METHODS: Three
repetitions of the CMFIF performed by eight novice and eight advanced female
gymnasts were recorded using a motion capture system. Optimal aerial techniques
that maximise rotation potential at regrasp were also computed. A 14-segment
multibody-model defined through the Rigid Body Dynamics Library was used to
compute recorded and optimal kinematics, and biomechanical parameters. A stepwise
multiple linear regression was used to determine the relative contribution of
these parameters in novice recorded, novice optimised, advanced recorded and
advanced optimised trials. Finally, fixed effects of expertise and optimisation
were tested through a mixed-effects analysis. RESULTS AND DISCUSSION: Variation
in release state only contributed to performances in novice recorded trials.
Moment of inertia contribution to performance increased from novice recorded, to
novice optimised, advanced recorded, and advanced optimised trials. Contribution
to performance of momentum transfer to the trunk during the flight prevailed in
all recorded trials. Although optimisation decreased transfer contribution,
momentum transfer to the arms appeared. CONCLUSION: Findings suggest that novices
should be coached on both contact and aerial technique. Inversely, mainly
improved aerial technique helped advanced gymnasts increase their performance.
For both, reduction of the moment of inertia should be focused on. The method
proposed in this article could be generalized to any aerial skill learning
investigation.
PMID- 28422955
TI - Low cholesterol level associated with severity and outcome of spontaneous
intracerebral hemorrhage: Results from Taiwan Stroke Registry.
AB - The relationship between cholesterol level and hemorrhagic stroke is
inconclusive. We hypothesized that low cholesterol levels may have association
with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes.
This study used data obtained from a multi-center stroke registry program in
Taiwan. We categorized acute spontaneous ICH patients, based on their baseline
levels of total cholesterol (TC) measured at admission, into 3 groups with <160,
160-200 and >200 mg/dL of TC. We evaluated risk of having initial stroke
severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and
unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality)
after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5+/-14.2
years; 64.2% men) were included in this study and 854 (34.9%) of them had
baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe
neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95%
confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11
1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL
and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR
3.94, 95% CI 1.76-8.80). Prior use of lipid-lowering drugs (2.8% of the ICH
population) was not associated with initial severity and 3-month outcomes. A
total cholesterol level lower than 160 mg/dL was common in patients with acute
ICH and was associated with greater neurological severity on presentation and
poor 3-month outcomes, especially with lower BMI.
PMID- 28422956
TI - Chronic activation of PPARalpha with fenofibrate reduces autophagic proteins in
the liver of mice independent of FGF21.
AB - Autophagy is a catabolic mechanism to degrade cellular components to maintain
cellular energy levels during starvation, a condition where PPARalpha may be
activated. Here we report a reduced autophagic capacity in the liver following
chronic activation of PPARalpha with fenofibrate (FB) in mice. Chronic
administration of the PPARalpha agonist FB substantially reduced the levels of
multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1)
which were associated with a decrease in the light chain LC3II/LC3I ratio and the
accumulation of p62. This was concomitant with an increase in the expression of
lipogenic proteins mSREBP1c, ACC, FAS and SCD1. These effects of FB were
completely abolished in PPARalpha-/- mice but remained intact in mice with global
deletion of FGF21, a key downstream mediator for PPARalpha-induced effects.
Further studies showed that decreased the content of autophagy proteins by FB was
associated with a significant reduction in the level of FoxO1, a transcriptional
regulator of autophagic proteins, which occurred independently of both mTOR and
Akt. These findings suggest that chronic stimulation of PPARalpha may suppress
the autophagy capacity in the liver as a result of reduced content of a number of
autophagy-associated proteins independent of FGF21.
PMID- 28422957
TI - Towards a theory of cortical columns: From spiking neurons to interacting neural
populations of finite size.
AB - Neural population equations such as neural mass or field models are widely used
to study brain activity on a large scale. However, the relation of these models
to the properties of single neurons is unclear. Here we derive an equation for
several interacting populations at the mesoscopic scale starting from a
microscopic model of randomly connected generalized integrate-and-fire neuron
models. Each population consists of 50-2000 neurons of the same type but
different populations account for different neuron types. The stochastic
population equations that we find reveal how spike-history effects in single
neuron dynamics such as refractoriness and adaptation interact with finite-size
fluctuations on the population level. Efficient integration of the stochastic
mesoscopic equations reproduces the statistical behavior of the population
activities obtained from microscopic simulations of a full spiking neural network
model. The theory describes nonlinear emergent dynamics such as finite-size
induced stochastic transitions in multistable networks and synchronization in
balanced networks of excitatory and inhibitory neurons. The mesoscopic equations
are employed to rapidly integrate a model of a cortical microcircuit consisting
of eight neuron types, which allows us to predict spontaneous population
activities as well as evoked responses to thalamic input. Our theory establishes
a general framework for modeling finite-size neural population dynamics based on
single cell and synapse parameters and offers an efficient approach to analyzing
cortical circuits and computations.
PMID- 28422958
TI - Modern alongside traditional taxonomy-Integrative systematics of the genera
Gymnangium Hincks, 1874 and Taxella Allman, 1874 (Hydrozoa, Aglaopheniidae).
AB - We studied the diversity within the former genus Gymnangium in the South West
Indian Ocean by using an integrative approach of both traditional (morphology
based) and modern molecular taxonomy. Nine species were recorded in the material
collected. A total of 97 16S mitochondrial DNA sequences and 54 Calmodulin
nuclear sequences from eight Gymnangium/Taxella species were analyzed. We found
both morphological and molecular differences in the studied Gymnangium species
that make it necessary to split the genus. It is proposed to revalidate the genus
Taxella which is currently regarded as a synonym of Gymnangium. Two species of
the genus Taxella (T. eximia and T. gracilicaulis), until now regarded as
distinct species based on morphological characteristics, cluster together in one
phylogenetic clade. Possible explanations are discussed. Two species from
Madagascar new to science are herein described and rare species from the Indian
Ocean islands are re-described.
PMID- 28422959
TI - Molecular regionalization of the developing amphioxus neural tube challenges
major partitions of the vertebrate brain.
AB - All vertebrate brains develop following a common Bauplan defined by
anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely
conserved differential expression of gene markers. However, it is still unclear
how this Bauplan originated during evolution. We studied the relative expression
of 48 genes with key roles in vertebrate neural patterning in a representative
amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central
nervous system (CNS) from a neural plate that is homologous to that of
vertebrates, allowing direct topological comparisons. The resulting
genoarchitectonic model revealed that the amphioxus incipient neural tube is
unexpectedly complex, consisting of several AP and DV molecular partitions.
Strikingly, comparison with vertebrates indicates that the vertebrate thalamus,
pretectum, and midbrain domains jointly correspond to a single amphioxus region,
which we termed Di-Mesencephalic primordium (DiMes). This suggests that these
domains have a common developmental and evolutionary origin, as supported by
functional experiments manipulating secondary organizers in zebrafish and mice.
PMID- 28422960
TI - Predicting the impact of Lynch syndrome-causing missense mutations from
structural calculations.
AB - Accurate methods to assess the pathogenicity of mutations are needed to fully
leverage the possibilities of genome sequencing in diagnosis. Current data-driven
and bioinformatics approaches are, however, limited by the large number of new
variations found in each newly sequenced genome, and often do not provide direct
mechanistic insight. Here we demonstrate, for the first time, that saturation
mutagenesis, biophysical modeling and co-variation analysis, performed in silico,
can predict the abundance, metabolic stability, and function of proteins inside
living cells. As a model system, we selected the human mismatch repair protein,
MSH2, where missense variants are known to cause the hereditary cancer
predisposition disease, known as Lynch syndrome. We show that the majority of
disease-causing MSH2 mutations give rise to folding defects and proteasome
dependent degradation rather than inherent loss of function, and accordingly our
in silico modeling data accurately identifies disease-causing mutations and
outperforms the traditionally used genetic disease predictors. Thus, in
conclusion, in silico biophysical modeling should be considered for making
genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps
other hereditary diseases.
PMID- 28422961
TI - Characterization of the mechanism of drug-drug interactions from PubMed using
MeSH terms.
AB - Identifying drug-drug interaction (DDI) is an important topic for the development
of safe pharmaceutical drugs and for the optimization of multidrug regimens for
complex diseases such as cancer and HIV. There have been about 150,000
publications on DDIs in PubMed, which is a great resource for DDI studies. In
this paper, we introduced an automatic computational method for the systematic
analysis of the mechanism of DDIs using MeSH (Medical Subject Headings) terms
from PubMed literature. MeSH term is a controlled vocabulary thesaurus developed
by the National Library of Medicine for indexing and annotating articles. Our
method can effectively identify DDI-relevant MeSH terms such as drugs, proteins
and phenomena with high accuracy. The connections among these MeSH terms were
investigated by using co-occurrence heatmaps and social network analysis. Our
approach can be used to visualize relationships of DDI terms, which has the
potential to help users better understand DDIs. As the volume of PubMed records
increases, our method for automatic analysis of DDIs from the PubMed database
will become more accurate.
PMID- 28422963
TI - A large-scale analysis of sex differences in facial expressions.
AB - There exists a stereotype that women are more expressive than men; however,
research has almost exclusively focused on a single facial behavior, smiling. A
large-scale study examines whether women are consistently more expressive than
men or whether the effects are dependent on the emotion expressed. Studies of
gender differences in expressivity have been somewhat restricted to data
collected in lab settings or which required labor-intensive manual coding. In the
present study, we analyze gender differences in facial behaviors as over 2,000
viewers watch a set of video advertisements in their home environments. The
facial responses were recorded using participants' own webcams. Using a new
automated facial coding technology we coded facial activity. We find that women
are not universally more expressive across all facial actions. Nor are they more
expressive in all positive valence actions and less expressive in all negative
valence actions. It appears that generally women express actions more frequently
than men, and in particular express more positive valence actions. However,
expressiveness is not greater in women for all negative valence actions and is
dependent on the discrete emotional state.
PMID- 28422962
TI - Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic
steatohepatitis in obese Ldlr-/- mice.
AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health
concern in western societies. Nonalcoholic steatohepatitis (NASH), the
progressive form of NAFLD, is characterized by hepatic steatosis, inflammation,
oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and
hepatocellular carcinoma. NASH is predicted to be the leading cause of liver
transplants by 2020. Despite this growing public health concern, there remain no
Food and Drug Administration (FDA) approved NASH treatments. Using Ldlr -/- mice
as a preclinical model of western diet (WD)-induced NASH, we previously
established that dietary supplementation with docosahexaenoic acid (DHA,
22:6,omega3) attenuated WD-induced NASH in a prevention study. Herein, we
evaluated the capacity of DHA supplementation of the WD and a low fat diet to
fully reverse NASH in mice with pre-existing disease. METHODS: Ldlr -/- mice fed
the WD for 22 wks developed metabolic syndrome (MetS) and a severe NASH
phenotype, including obesity, dyslipidemia, hyperglycemia, hepatic steatosis,
inflammation, fibrosis and low hepatic polyunsaturated fatty acid (PUFA) content.
These mice were randomized to 5 groups: a baseline group (WDB, sacrificed at 22
wks) and 4 treatments: 1) WD + olive oil (WDO); 2) WD + DHA (WDD); 3) returned to
chow + olive oil (WDChO); or 4) returned to chow + DHA (WDChD). The four
treatment groups were maintained on their respective diets for 8 wks. An
additional group was maintained on standard laboratory chow (Reference Diet, RD)
for the 30-wk duration of the study. RESULTS: When compared to the WDB group, the
WDO group displayed increased hepatic expression of genes linked to inflammation
(Opn, Il1rn, Gdf15), hepatic fibrosis (collagen staining, Col1A1, Thbs2, Lox)
reflecting disease progression. Mice in the WDD group, in contrast, had increased
hepatic C20-22 omega3 PUFA and no evidence of NASH progression. MetS and NASH
markers in the WDChO or WDChD groups were significantly attenuated and marginally
different from the RD group, reflecting disease remission. CONCLUSION: While
these studies establish that DHA supplementation of the WD blocks WD-induced NASH
progression, DHA alone does not promote full remission of diet-induced MetS or
NASH.
PMID- 28422964
TI - Effect of women's age on embryo morphology, cleavage rate and competence-A
multicenter cohort study.
AB - This multicenter cohort study on embryo assessment and outcome data from 11,744
IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of
women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well
as cycle outcome measures corrected for confounding factors as center, partner's
age and referral diagnosis. Cycle outcome data confirmed the well-known effect of
women's age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN)
zygotes were not affected by age, while a significant increase in 3PN zygotes was
observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no
effect on cleavage parameters or on the morphology of the embryo day 2 post
insemination. Interestingly, initial hCG value after single embryo transfer
followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and
ICSI (p = 0.001) cycles. For the first time, we show that a woman's age does
impose a significant footprint on early embryo morphological development (3PN).
In addition, the developmentally competent embryos were associated with increased
initial hCG values as the age of the women increased. Further studies are needed
to elucidate, if this increase in initial hCG value with advancing maternal age
is connected to the embryo or the uterus.
PMID- 28422965
TI - Diet and condition of mesopredators on coral reefs in relation to shark
abundance.
AB - Reef sharks may influence the foraging behaviour of mesopredatory teleosts on
coral reefs via both risk effects and competitive exclusion. We used a "natural
experiment" to test the hypothesis that the loss of sharks on coral reefs can
influence the diet and body condition of mesopredatory fishes by comparing two
remote, atoll-like reef systems, the Rowley Shoals and the Scott Reefs, in
northwestern Australia. The Rowley Shoals are a marine reserve where sharks are
abundant, whereas at the Scott Reefs numbers of sharks have been reduced by
centuries of targeted fishing. On reefs where sharks were rare, the gut contents
of five species of mesopredatory teleosts largely contained fish while on reefs
with abundant sharks, the same mesopredatory species consumed a larger proportion
of benthic invertebrates. These measures of diet were correlated with changes in
body condition, such that the condition of mesopredatory teleosts was
significantly poorer on reefs with higher shark abundance. Condition was defined
as body weight, height and width for a given length and also estimated via
several indices of condition. Due to the nature of natural experiments,
alternative explanations cannot be discounted. However, the results were
consistent with the hypothesis that loss of sharks may influence the diet and
condition of mesopredators and by association, their fecundity and trophic role.
Regardless of the mechanism (risk effects, competitive release, or other), our
findings suggest that overfishing of sharks has the potential to trigger trophic
cascades on coral reefs and that further declines in shark populations globally
should be prevented to protect ecosystem health.
PMID- 28422966
TI - Taming the late Quaternary phylogeography of the Eurasiatic wild ass through
ancient and modern DNA.
AB - Taxonomic over-splitting of extinct or endangered taxa, due to an incomplete
knowledge of both skeletal morphological variability and the geographical ranges
of past populations, continues to confuse the link between isolated extant
populations and their ancestors. This is particularly problematic with the genus
Equus. To more reliably determine the evolution and phylogeographic history of
the endangered Asiatic wild ass, we studied the genetic diversity and inter
relationships of both extinct and extant populations over the last 100,000 years,
including samples throughout its previous range from Western Europe to Southwest
and East Asia. Using 229 bp of the mitochondrial hypervariable region, an
approach which allowed the inclusion of information from extremely poorly
preserved ancient samples, we classify all non-African wild asses into eleven
clades that show a clear phylogeographic structure revealing their phylogenetic
history. This study places the extinct European wild ass, E. hydruntinus, the
phylogeny of which has been debated since the end of the 19th century, into its
phylogenetic context within the Asiatic wild asses and reveals recent
mitochondrial introgression between populations currently regarded as separate
species. The phylogeographic organization of clades resulting from these efforts
can be used not only to improve future taxonomic determination of a poorly
characterized group of equids, but also to identify historic ranges,
interbreeding events between various populations, and the impact of ancient
climatic changes. In addition, appropriately placing extant relict populations
into a broader phylogeographic and genetic context can better inform ongoing
conservation strategies for this highly-endangered species.
PMID- 28422967
TI - Craniodental and humeral morphology of a new species of Masrasector
(Teratodontinae, Hyaenodonta, Placentalia) from the late Eocene of Egypt and
locomotor diversity in hyaenodonts.
AB - Hyaenodonta is a diverse clade of carnivorous mammals that were part of
terrestrial faunas in the Paleogene of Eurasia and North America, but the oldest
record for the group is Afro-Arabian, making the record there vital for
understanding the evolution of this wide-spread group. Previous studies show an
ancient split between two major clades of hyaenodonts that converged in
hypercarnivory: Hyainailourinae and Hyaenodontinae. These clades are each
supported by cranial characters. Phylogenetic analyses of hyaenodonts also
support the monophyly of Teratodontinae, an Afro-Arabian clade of mesocarnivorous
to hypercarnivorous hyaenodonts. Unfortunately, the cranial anatomy of
teratodontines is poorly known, and aligning the clade with other lineages has
been difficult. Here, a new species of the phylogenetically controversial
teratodontine Masrasector is described from Locality 41 (latest Priabonian, late
Eocene) from the Fayum Depression, Egypt. The hypodigm includes the most complete
remains of a Paleogene teratodontine, including largely complete crania, multiple
dentaries, and isolated humeri. Standard and "tip-dating" Bayesian analyses of a
character-taxon matrix that samples cranial, postcranial, and dental characters
support a monophyletic Masrasector within Teratodontinae, which is consistently
placed as a close sister group of Hyainailouridae. The cranial morphology of
Masrasector provides new support for an expanded Hyainailouroidea (Teratodontinae
+ Hyainailouridae), particularly characters of the nuchal crest, palate, and
basicranium. A discriminant function analysis was performed using measurements of
the distal humerus from a diverse sample of extant carnivorans to infer the
locomotor habits of Masrasector. Masrasector was assigned to the "terrestrial"
locomotor category, a result consistent with the well-defined medial trochlear
ridges, and moderately developed supinator crests of the specimens. Masrasector
appears to have been a fast-moving terrestrial form with a diverse diet. These
specimens considerably improve our understanding of Teratodontinae, an ancient
member of the Afro-Arabian mammalian fauna, and our understanding of hyaenodont
diversity before the dispersal of Carnivora to the continent near the end of the
Paleogene.
PMID- 28422968
TI - The impact of a point-of-care testing device on CVD risk assessment completion in
New Zealand primary-care practice: A cluster randomised controlled trial and
qualitative investigation.
AB - OBJECTIVES: To assess the effect of a point of care (POC) device for testing
lipids and HbA1c in addition to testing by community laboratory facilities (usual
practice) on the completion of cardiovascular disease (CVD) risk assessments in
general practice. METHODS: We conducted a pragmatic, cluster randomised
controlled trial in 20 New Zealand general practices stratified by size and
rurality and randomised to POC device plus usual practice or usual practice alone
(controls). Patients aged 35-79 years were eligible if they met national
guideline criteria for CVD risk assessment. Data on CVD risk assessments were
aggregated using a web-based decision support programme common to each practice.
Data entered into the on-line CVD risk assessment form could be saved pending
blood test results. The primary outcome was the proportion of completed CVD risk
assessments. Qualitative data on practice processes for CVD risk assessment and
feasibility of POC testing were collected at the end of the study by interviews
and questionnaire. The POC testing was supported by a comprehensive quality
assurance programme. RESULTS: A CVD risk assessment entry was recorded for 7421
patients in 10 POC practices and 6217 patients in 10 control practices; 99.5% of
CVD risk assessments had complete data in both groups (adjusted odds ratio 1.02
[95%CI 0.61-1.69]). There were major external influences that affected the trial:
including a national performance target for CVD risk assessment and changes to
CVD guidelines. All practices had invested in systems and dedicated staff time to
identify and follow up patients to completion. However, the POC device was viewed
by most as an additional tool rather than as an opportunity to review practice
work flow and leverage the immediate test results for patient education and CVD
risk management discussions. Shortly after commencement, the trial was halted due
to a change in the HbA1c test assay performance. The trial restarted after the
manufacturing issue was rectified but this affected the end use of the device.
CONCLUSIONS: Performance incentives and external influences were more powerful
modifiers of practice behaviours than the POC device in relation to CVD risk
assessment completion. The promise of combining risk assessment, communication
and management within one consultation was not realised. With shifts in policy
focus, the utility of POC devices for patient engagement in CVD preventive care
may be demonstrated if fully integrated into the clinical setting. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12613000607774.
PMID- 28422969
TI - A new species of Tometes Valenciennes 1850 (Characiformes: Serrasalmidae) from
Tocantins-Araguaia River Basin based on integrative analysis of molecular and
morphological data.
AB - A new large serrasalmid species of Tometes is described from the Tocantins
Araguaia River Basin. Tometes siderocarajensis sp. nov. is currently found in the
rapids of the Itacaiunas River Basin, and formerly inhabited the lower Tocantins
River. The new species can be distinguished from all congeners, except from T.
ancylorhynchus, by the presence of lateral space between 1st and 2nd premaxillary
teeth, and by the absence of lateral cusps in these two teeth. However, T.
siderocarajensis sp. nov. can be differentiated from syntopic congener T.
ancylorhynchus by an entirely black with mottled red body in live specimens,
densely pigmented pelvic fins with a high concentration of dark chromatophores,
and the presence of 39 to 41 rows of circumpeduncular scales (vs. silvery body
coloration with slightly reddish overtones on middle flank during breeding period
in live specimens, hyaline to slightly pale coloration on distalmost region of
pelvic fins, and 30 to 36 rows of circumpeduncular scales). Additionally,
molecular sequence shows that T. siderocarajensis sp. nov. is reciprocally
monophyletic, and diagnosable from all congeners by having two autapomorphic
molecular characters in the mitochondrial gene COI. The phylogenetic
reconstruction still show that T. siderocarajensis sp. nov. is closely related to
T. trilobatus. This is the first molecular study using an integrative taxonomic
approach based on morphological and molecular sequence data for all described
species of Tometes. These findings increase the number of formally described
species of Tometes to seven. A key to the Tometes species is provided.
PMID- 28422970
TI - The gut microbiota as a modulator of innate immunity during melioidosis.
AB - BACKGROUND: Melioidosis, caused by the Gram-negative bacterium Burkholderia
pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics.
The gut microbiota supports local mucosal immunity and is increasingly recognized
as a protective mediator in host defenses against systemic infection. Here, we
aimed to characterize the composition and function of the intestinal microbiota
during experimental melioidosis. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice
were infected intranasally with B. pseudomallei and sacrificed at different time
points to assess bacterial loads and inflammation. In selected experiments, the
gut microbiota was disrupted with broad-spectrum antibiotics prior to
inoculation. Fecal bacterial composition was analyzed by means of IS-pro, a 16S
23S interspacer region-based profiling method. A marked shift in fecal bacterial
composition was seen in all mice during systemic B. pseudomallei infection with a
strong increase in Proteobacteria and decrease in Actinobacteria, with an
increase in bacterial diversity. We found enhanced early dissemination of B.
pseudomallei and systemic inflammation during experimental melioidosis in
microbiota-disrupted mice compared with controls. Whole-genome transcriptional
profiling of the lung identified several genes that were differentially expressed
between mice with a normal or disrupted intestinal microbiota. Genes involved in
acute phase signaling, including macrophage-related signaling pathways were
significantly elevated in microbiota disrupted mice. Compared with controls,
alveolar macrophages derived from antibiotic pretreated mice showed a diminished
capacity to phagocytose B. pseudomallei. This might in part explain the observed
protective effect of the gut microbiota in the host defense against pneumonia
derived melioidosis. CONCLUSIONS/SIGNIFICANCE: Taken together, these data
identify the gut microbiota as a potential modulator of innate immunity during B.
pseudomallei infection.
PMID- 28422971
TI - Comparison of chemical-use between hydraulic fracturing, acidizing, and routine
oil and gas development.
AB - The potential hazards and risks associated with well-stimulation in
unconventional oil and gas development (hydraulic fracturing, acid fracturing,
and matrix acidizing) have been investigated and evaluated and federal and state
regulations requiring chemical disclosure for well-stimulation have been
implemented as part of an overall risk management strategy for unconventional oil
and gas development. Similar evaluations for chemicals used in other routine oil
and gas development activities, such as maintenance acidizing, gravel packing,
and well drilling, have not been previously conducted, in part due to a lack of
reliable information concerning on-field chemical-use. In this study, we compare
chemical-use between routine activities and the more closely regulated well
stimulation activities using data collected by the South Coast Air Quality
Monitoring District (SCAQMD), which mandates the reporting of both unconventional
and routine on-field chemical-use for parts of Southern California. Analysis of
this data shows that there is significant overlap in chemical-use between so
called unconventional activities and routine activities conducted for well
maintenance, well-completion, or rework. A comparison within the SCAQMD shows a
significant overlap between both types and amounts of chemicals used for well
stimulation treatments included under State mandatory-disclosure regulations and
routine treatments that are not included under State regulations. A comparison
between SCAQMD chemical-use for routine treatments and state-wide chemical-use
for hydraulic fracturing also showed close similarity in chemical-use between
activities covered under chemical disclosure requirements (e.g. hydraulic
fracturing) and many other oil and gas field activities. The results of this
study indicate regulations and risk assessments focused exclusively on chemicals
used in well-stimulation activities may underestimate potential hazard or risk
from overall oil field chemical-use.
PMID- 28422973
TI - Camera trap arrays improve detection probability of wildlife: Investigating study
design considerations using an empirical dataset.
AB - Camera trapping is a standard tool in ecological research and wildlife
conservation. Study designs, particularly for small-bodied or cryptic wildlife
species often attempt to boost low detection probabilities by using non-random
camera placement or baited cameras, which may bias data, or incorrectly estimate
detection and occupancy. We investigated the ability of non-baited, multi-camera
arrays to increase detection probabilities of wildlife. Study design components
were evaluated for their influence on wildlife detectability by iteratively
parsing an empirical dataset (1) by different sizes of camera arrays deployed (1
10 cameras), and (2) by total season length (1-365 days). Four species from our
dataset that represented a range of body sizes and differing degrees of presumed
detectability based on life history traits were investigated: white-tailed deer
(Odocoileus virginianus), bobcat (Lynx rufus), raccoon (Procyon lotor), and
Virginia opossum (Didelphis virginiana). For all species, increasing from a
single camera to a multi-camera array significantly improved detection
probability across the range of season lengths and number of study sites
evaluated. The use of a two camera array increased survey detection an average of
80% (range 40-128%) from the detection probability of a single camera across the
four species. Species that were detected infrequently benefited most from a
multiple-camera array, where the addition of up to eight cameras produced
significant increases in detectability. However, for species detected at high
frequencies, single cameras produced a season-long (i.e, the length of time over
which cameras are deployed and actively monitored) detectability greater than
0.75. These results highlight the need for researchers to be critical about
camera trap study designs based on their intended target species, as
detectability for each focal species responded differently to array size and
season length. We suggest that researchers a priori identify target species for
which inference will be made, and then design camera trapping studies around the
most difficult to detect of those species.
PMID- 28422972
TI - Challenges in enumeration of CTCs in breast cancer using techniques independent
of cytokeratin expression.
AB - INTRODUCTION: Given the current postulated plasticity between epithelial and
mesenchymal states of migratory cancer cells the detection of non-epithelial CTCs
is an important scientific and clinical goal. METHODS: We used the filtration
based ISET technology to enrich circulating tumour cells (CTCs) in early breast
cancer blood samples and identify them using a morphology-based
immunocytochemistry (ICC) approach. RESULTS: We found greater numbers of putative
CTCs by this approach than by the cytokeratin-based CellSearch technology, but a
high number of CTC false positives were identified in healthy volunteer samples
which were not reduced in successive blood draws. Preliminary work using an
oestrogen receptor (ER)-based multiplex ICC method in metastatic breast cancer
ISET samples indicated a low number of ER+ CTCs even at this advanced stage.
CONCLUSIONS: This work highlights the challenges in enumerating CTCs without
conventional epithelial markers.
PMID- 28422974
TI - Variation in benthic long-term data of transitional waters: Is interpretation
more than speculation?
AB - Biological long-term data series in marine habitats are often used to identify
anthropogenic impacts on the environment or climate induced regime shifts.
However, particularly in transitional waters, environmental properties like water
mass dynamics, salinity variability and the occurrence of oxygen minima not
necessarily caused by either human activities or climate change can attenuate or
mask apparent signals. At first glance it very often seems impossible to
interpret the strong fluctuations of e.g. abundances or species richness, since
abiotic variables like salinity and oxygen content vary simultaneously as well as
in apparently erratic ways. The long-term development of major macrozoobenthic
parameters (abundance, biomass, species numbers) and derivative macrozoobenthic
indices (Shannon diversity, Margalef, Pilou's evenness and Hurlbert) has been
successfully interpreted and related to the long-term fluctuations of salinity
and oxygen, incorporation of the North Atlantic Oscillation index (NAO index),
relying on the statistical analysis of modelled and measured data during 35 years
of observation at three stations in the south-western Baltic Sea. Our results
suggest that even at a restricted spatial scale the benthic system does not
appear to be tightly controlled by any single environmental driver and highlight
the complexity of spatially varying temporal response.
PMID- 28422975
TI - Children's weight changes according to maternal perception of the child's weight
and health: A prospective cohort of Peruvian children.
AB - The aim of the study was to estimate the association between maternal perception
of their child's health status and (mis)classification of their child's actual
weight with future weight change. We present cross-sectional and longitudinal
analyses from the Peruvian younger cohort of the Young Lives Study. For cross
sectional analysis, the exposure was maternal perception of child health status
(better, same or worse); the outcome was underestimation or overestimation of the
child's actual weight. Mothers were asked about their perception of their child's
weight (same, lighter or heavier than other children). Actual weight status was
defined with IOTF BMI cut-off points. For longitudinal analysis, the exposure was
(mis)classification of the child's actual weight; the outcome was the
standardized mean difference between follow-up and baseline BMI. A Generalized
Linear Model with Poisson family and log-link was used to report the prevalence
ratio (PR) and 95% confidence intervals (95% CI) for cross-sectional analyses. A
Linear Regression Model was used to report the longitudinal analysis as
coefficient estimates (beta) and 95% CI. Normal weight children who were
perceived as more healthy than other children were more likely to have their
weight overestimated (PR = 2.06); conversely, those who were perceived as less
healthy than other children were more likely to have their weight underestimated
(PR = 2.17). Mean follow-up time was 2.6 (SD: 0.3) years. Overall, underweight
children whose weight was overestimated were more likely to gain BMI (beta =
0.44); whilst overweight children whose weight was considered to be the same of
their peers (beta = -0.55), and those considered to be lighter than other
children (beta = -0.87), lost BMI. Maternal perception of the child's health
status seems to influence both overestimation and underestimation of the child's
actual weight status. Such weight (mis)perception may influence future BMI.
PMID- 28422976
TI - Reactivation or transformation? Motor memory consolidation associated with
cerebral activation time-locked to sleep spindles.
AB - Motor memory consolidation is thought to depend on sleep-dependent reactivation
of brain areas recruited during learning. However, up to this point, there has
been no direct evidence to support this assertion in humans, and the
physiological processes supporting such reactivation are unknown. Here,
simultaneous electroencephalographic and functional magnetic resonance imaging
(EEG-fMRI) recordings were conducted during post-learning sleep to directly
investigate the spindle-related reactivation of a memory trace formed during
motor sequence learning (MSL), and its relationship to overnight enhancement in
performance (reflecting consolidation). We show that brain regions within the
striato-cerebello-cortical network recruited during training on the MSL task, and
in particular the striatum, were also activated during sleep, time-locked to
spindles. Interestingly, the consolidated trace in the striatum was not simply
strengthened, but was transformed/reorganized from rostrodorsal (associative) to
caudoventral (sensorimotor) subregions. Moreover, the degree of the reactivation
was correlated with overnight improvements in performance. Altogether, the
present findings demonstrate that striatal reactivation linked to sleep spindles
in the post-learning night, is related to motor memory consolidation.
PMID- 28422977
TI - Defining the complex phenotype of severe systemic loxoscelism using a large
electronic health record cohort.
AB - OBJECTIVE: Systemic loxoscelism is a rare illness resulting from the bite of the
recluse spider and, in its most severe form, can lead to widespread hemolysis,
coagulopathy, and death. We aim to describe the clinical features and outcomes of
the largest known cohort of individuals with moderate to severe loxoscelism.
METHODS: We performed a retrospective, cross sectional study from January 1,
1995, to December 31, 2015, at a tertiary-care academic medical center, to
determine individuals with clinical records consistent with moderate to severe
loxoscelism. Age-, sex-, and race-matched controls were compared. Demographics,
clinical characteristics, laboratory measures, and outcomes of individuals with
loxoscelism are described. Case and control groups were compared with descriptive
statistics and phenome-wide association study (PheWAS). RESULTS: During the time
period, 57 individuals were identified as having moderate to severe loxoscelism.
Of these, only 33% had an antecedent spider bite documented. Median age of
individuals diagnosed with moderate to severe loxoscelism was 14 years old (IQR
9.0-24.0 years). PheWAS confirmed associations of systemic loxoscelism with 29
other phenotypes, e.g., rash, hemolytic anemia, and sepsis. Hemoglobin level
dropped an average of 3.1 g/dL over an average of 2.0 days (IQR 2.0-6.0). Lactate
dehydrogenase and total bilirubin levels were on average over two times their
upper limit of normal values. Eighteen individuals of 32 tested had a positive
direct antiglobulin (Coombs') test. Mortality was 3.5% (2/57 individuals).
CONCLUSION: Systemic loxoscelism is a rare but devastating process with only a
minority of patients recalling the toxic exposure; hemolysis reaches a peak at 2
days after admission, with some cases taking more than a week before recovery. In
endemic areas, suspicion for systemic loxoscelism should be high in individuals,
especially children and younger adults, presenting with a cutaneous ulcer and
hemolysis or coagulopathy, even in the absence of a bite exposure history.
PMID- 28422978
TI - The ESCRT regulator Did2 maintains the balance between long-distance endosomal
transport and endocytic trafficking.
AB - In highly polarised cells, like fungal hyphae, early endosomes function in both
endocytosis as well as long-distance transport of various cargo including mRNA
and protein complexes. However, knowledge on the crosstalk between these
seemingly different trafficking processes is scarce. Here, we demonstrate that
the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of
Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less
processive long-distance transport and abnormal shuttling of early endosomes.
Importantly, the late endosomal protein Rab7 and vacuolar protease Prc1 exhibit
increased shuttling on these aberrant endosomes suggesting defects in endosomal
maturation and identity. Consistently, molecular motors fail to attach
efficiently explaining the disturbed processive movement. Furthermore, the
endosomal mRNP linker protein Upa1 is hardly present on endosomes resulting in
defects in long-distance mRNA transport. In conclusion, the ESCRT regulator Did2
coordinates precise maturation of endosomes and thus provides the correct
membrane identity for efficient endosomal long-distance transport.
PMID- 28422979
TI - Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in
lung adenocarcinoma.
AB - BACKGROUND: 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography
(PET) is a functional imaging modality based on glucose metabolism. The
correlation between EGFR or KRAS mutation status and the standardized uptake
value (SUV) of 18F-FDG PET scanning has not been fully elucidated. METHODS:
Correlations between EGFR or KRAS mutation status and clinicopathological factors
including SUVmax were statistically analyzed in 734 surgically resected lung
adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS
mutation status and glucose metabolism were then elucidated in 62 lung
adenocarcinomas using cap analysis of gene expression (CAGE), a method to
determine and quantify the transcription initiation activities of mRNA across the
genome. RESULTS: EGFR and KRAS mutations were detected in 334 (46%) and 83 (11%)
of the 734 lung adenocarcinomas, respectively. The remaining 317 (43%) patients
had wild-type tumors for both genes. EGFR mutations were more frequent in tumors
with lower SUVmax. In contrast, no relationship was noted between KRAS mutation
status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism
(GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1,
CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although
expression levels were lower in EGFR-mutated than in wild-type tumors. No similar
relationships were noted with KRAS mutations. CONCLUSIONS: EGFR-mutated
adenocarcinomas are biologically indolent with potentially lower levels of
glucose metabolism than wild-type tumors. Several genes associated with glucose
metabolism and the cell cycle were specifically down-regulated in EGFR-mutated
adenocarcinomas.
PMID- 28422980
TI - Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to
Plasmodium falciparum.
AB - Multiple mechanisms such as genetic and epigenetic variations within a key gene
may play a role in malarial susceptibility and response to anti-malarial drugs in
the population. ABCB1 is one of the well-studied membrane transporter genes that
code for the P-glycoprotein (an efflux protein) and whose effect on malaria
disease predisposition and susceptibility to drugs remains to be understood. We
studied the association of single nucleotide variations in human ABCB1 that
influences its function in subjects with uncomplicated and complicated malaria
caused by Plasmodium falciparum (Pf). Global DNA methylation and ABCB1 DNA
promoter methylation levels were performed along with transcriptional response
and protein expression in subjects with malaria and healthy controls. The
rs2032582 locus was significantly associated with complicated and combined
malaria groups when compared to controls (p < 0.05). Significant DNA methylation
difference was noticed between case and control (p < 0.05). In addition, global
DNA methylation levels of the host DNA were inversely proportional to parasitemia
in individuals with Pf infection. Our study also revealed the correlation between
ABCB1 DNA promoter methylation with rs1128503 and rs2032582 polymorphisms in
malaria and was related to increased expression of ABCB1 protein levels in
complicated malaria group (p < 0.05) when compared to uncomplicated malaria and
control groups. The study provides evidence for multiple mechanisms that may
regulate the role of host ABCB1 function to mediate aetiology of malaria
susceptibility, prognosis and drug response. These may have clinical implications
and therapeutic application for various malarial conditions.
PMID- 28422981
TI - QTL analysis and dissection of panicle components in rice using advanced
backcross populations derived from Oryza Sativa cultivars HR1128 and
'Nipponbare'.
AB - Panicle traits are among the most important agronomic characters which directly
relate to yield in rice. Grain number (GN), panicle length (PL), primary branch
number (PBN), and secondary branch number (SBN) are the major components of rice
panicle structure, and are all controlled by quantitative trait loci (QTLs). In
our research, four advanced backcross overlapping populations (BIL152, BIL196a,
BIL196b, and BIL196b-156) carrying introgressed segments from chromosome 6 were
derived from an indica/japonica cross that used the super-hybrid rice restorer
line HR1128 and the international sequenced japonica cultivar 'Nipponbare' as the
donor and recurrent parents, respectively. The four panicle traits, GN, PL, PBN,
and SBN, were evaluated for QTL effects using the inclusive composite interval
mapping (ICIM) method in populations over two years at two sites. Results showed
that a total of twelve QTLs for GN, PL, PBN, and SBN were detected on chromosome
6. Based on marker loci physical positions, the QTLs were found to be tightly
linked to three important chromosomal intervals described as RM7213 to RM19962,
RM20000 to RM20210, and RM412 to RM20595. Three QTLs identified in this study,
PL6-5, PBN6-1, and PBN6-2, were found to be novel compared with previous studies.
A major QTL (PL6-5) for panicle length was detected in all four populations at
two locations, and its position was narrowed down to a 1.3Mb region on chromosome
6. Near isogenic lines (NILs) carrying PL6-5 will be developed for fine mapping
of the QTL, and our results will provide referable information for gene
excavation of panicle components in rice.
PMID- 28422982
TI - Assessment ecological risk of heavy metal caused by high-intensity land
reclamation in Bohai Bay, China.
AB - The article examines the detailed spatial and temporal distributions of coastal
reclamation in the northwest coast of Bohai Bay experiencing rapid coastal
reclamation in China from 1974 to 2010 in annual intervals. Moreover, soil
elements properties and spatial distribution in reclaimed area and inform the
future coastal ecosystems management was also analyzed. The results shows that
910.7 km2 of coastal wetlands have been reclaimed and conversed to industrial
land during the past 36 years. It covers intertidal beach, shallow sea and island
with a percentage of 76.0%, 23.5% and 0.5%, respectively. The average
concentration of Mn is 686.91mg/kg and the order of concentration of heavy metal
are Cr>Zn>As>Ni>Cu>Pb>Cd>Hg. We used the "space for time substitution" method to
test the soil properties changes after reclamation. The potential ecological risk
of heavy metal is in low level and the risk of Cd and As is relatively higher.
The ecosystem-based coastal protection and management are urgent to support
sustainable coastal ecosystems in Bohai bay in the future.
PMID- 28422983
TI - KIAA1199 promotes migration and invasion by Wnt/beta-catenin pathway and MMPs
mediated EMT progression and serves as a poor prognosis marker in gastric cancer.
AB - BACKGROUND: KIAA1199 was upregulated in diverse cancers, but the association of
KIAA1199 with gastric cancer (GC), the biological role of KIAA1199 in GC cells
and the related molecular mechanisms remain to be elucidated. METHODS: KIAA1199
expression was analysed by reverse transcription-polymerase chain reaction assay
(RT-PCR) and immunohistochemistry (IHC) in GC patient tissue. The small hairpin
RNA (shRNA) was applied for the knockdown of endogenous KIAA1199 in NCI-N87 and
AGS cells. MTT, colony formation, scratch wounding migration, transwell chamber
migration and invasion assays were employed respectively to investigate the role
of KIAA1199 in GC cells. The potential signaling pathway of KIAA1199 induced
migration and invasion was detected. RESULTS: KIAA1199 was upregulated in GC
tissue and was an essential independent marker for poor prognosis. Knockdown
KIAA1199 suppressed the proliferation, migration and invasion in GC cells.
KIAA1199 stimulated the Wnt/beta-catenin signaling pathway and the enzymatic
activity of matrix metalloproteinase (MMP) family members and thus accelerated
the epithelial-to-mesenchymal transition (EMT) progression in GC cells.
CONCLUSION: These findings demonstrated that KIAA1199 was upregulated in GC
tissue and associated with worse clinical outcomes in GC, and KIAA1199 acted as
an oncogene by promoting migration and invasion through the enhancement of
Wnt/beta-catenin signaling pathway and MMPs mediated EMT progression in GC cells.
PMID- 28422984
TI - The impact of atosiban on pregnancy outcomes in women undergoing in vitro
fertilization-embryo transfer: A meta-analysis.
AB - BACKGROUND: Atosiban is administered to women undergoing in vitro fertilization
embryo transfer (IVF-ET) to improve pregnancy outcomes. However, the results of
this treatment were controversial. We conducted this meta-analysis to investigate
whether atosiban improves pregnancy outcomes in the women undergoing in vitro
fertilization (IVF). METHODS: Databases of PubMed, EMBASE, Web of Science, China
BioMedicine, and Google Scholar were systematically searched. Meta-analyses were
performed to investigate whether atosiban improves pregnancy outcomes in the
women undergoing IVF. RESULTS: Our results showed that atosiban was associated
with higher implantation (OR = 1.63, 95% CI: 1.17-2.27; P = 0.004) and clinical
pregnancy (OR = 1.84, 95% CI: 1.31-2.57; P < 0.001) rates. However, atosiban
showed no significant association with the miscarriage, live birth, multiple
pregnancy or ectopic pregnancy rates. When a further subgroup analysis was
performed in the women undergoing repeated implantation failure (RIF),
implantation (OR = 1.93, 95% CI: 1.45-2.57; P < 0.001), clinical pregnancy (OR =
2.48, 95% CI: 1.70-3.64; P <0.001) and the live birth (OR = 2.89, 95% CI: 1.78
4.67; P < 0.001) rates were significantly higher in the case group. Nevertheless,
no significant difference was detected in the miscarriage and multiple pregnancy
rates between the case and control groups. CONCLUSION: Atosiban may be more
appropriate for women undergoing RIF and play only a limited role in improving
pregnancy outcomes in the general population of women undergoing IVF. These
conclusions should be verified in large and well-designed studies.
PMID- 28422985
TI - Revising mtDNA haplotypes of the ancient Hungarian conquerors with next
generation sequencing.
AB - As part of the effort to create a high resolution representative sequence
database of the medieval Hungarian conquerors we have resequenced the entire
mtDNA genome of 24 published ancient samples with Next Generation Sequencing,
whose haplotypes had been previously determined with traditional PCR based
methods. We show that PCR based methods are prone to erroneous haplotype or
haplogroup determination due to ambiguous sequence reads, and many of the
resequenced samples had been classified inaccurately. The SNaPshot method applied
with published ancient DNA authenticity criteria is the most straightforward and
cheapest PCR based approach for testing a large number of coding region SNP-s,
which greatly facilitates correct haplogroup determination.
PMID- 28422986
TI - A critical-like collective state leads to long-range cell communication in
Dictyostelium discoideum aggregation.
AB - The transition from single-cell to multicellular behavior is important in early
development but rarely studied. The starvation-induced aggregation of the social
amoeba Dictyostelium discoideum into a multicellular slug is known to result from
single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate
(cAMP). However, how exactly do transient, short-range chemical gradients lead to
coherent collective movement at a macroscopic scale? Here, we developed a
multiscale model verified by quantitative microscopy to describe behaviors
ranging widely from chemotaxis and excitability of individual cells to
aggregation of thousands of cells. To better understand the mechanism of long
range cell-cell communication and hence aggregation, we analyzed cell-cell
correlations, showing evidence of self-organization at the onset of aggregation
(as opposed to following a leader cell). Surprisingly, cell collectives, despite
their finite size, show features of criticality known from phase transitions in
physical systems. By comparing wild-type and mutant cells with impaired
aggregation, we found the longest cell-cell communication distance in wild-type
cells, suggesting that criticality provides an adaptive advantage and optimally
sized aggregates for the dispersal of spores.
PMID- 28422988
TI - Rainfall changes affect the algae dominance in tank bromeliad ecosystems.
AB - Climate change and biodiversity loss have been reported as major disturbances in
the biosphere which can trigger changes in the structure and functioning of
natural ecosystems. Nonetheless, empirical studies demonstrating how both factors
interact to affect shifts in aquatic ecosystems are still unexplored. Here, we
experimentally test how changes in rainfall distribution and litter diversity
affect the occurrence of the algae-dominated condition in tank bromeliad
ecosystems. Tank bromeliads are miniature aquatic ecosystems shaped by the
rainwater and allochthonous detritus accumulated in the bases of their leaves.
Here, we demonstrated that changes in the rainfall distribution were able to
reduce the chlorophyll-a concentration in the water of bromeliad tanks affecting
significantly the occurrence of algae-dominated conditions. On the other hand,
litter diversity did not affect the algae dominance irrespective to the rainfall
scenario. We suggest that rainfall changes may compromise important self
reinforcing mechanisms responsible for maintaining high levels of algae on tank
bromeliads ecosystems. We summarized these results into a theoretical model which
suggests that tank bromeliads may show two different regimes, determined by the
bromeliad ability in taking up nutrients from the water and by the total amount
of light entering the tank. We concluded that predicted climate changes might
promote regime shifts in tropical aquatic ecosystems by shaping their structure
and the relative importance of other regulating factors.
PMID- 28422987
TI - Systematic review and meta-analysis shows a specific micronutrient profile in
people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red
blood cell copper and zinc, and higher salivary calcium and sodium.
AB - Different metabolic profiles as well as comorbidities are common in people with
Down Syndrome (DS). Therefore it is relevant to know whether micronutrient levels
in people with DS are also different. This systematic review was designed to
review the literature on micronutrient levels in people with DS compared to age
and sex-matched controls without DS. We identified sixty nine studies from
January 1967 to April 2016 through main electronic medical databases PubMed,
Scopus, and Web of knowledge. We carried out meta-analysis of the data on four
essential trace elements (Cu, Fe, Se, and Zn), six minerals (Ca, Cl, K, Mg, Na,
and P), and five vitamins (vitamin A, B9, B12, D, and E). People with DS showed
lower blood levels of Ca (standard mean difference (SMD) = -0.63; 95% confidence
interval (CI): -1.16 to -0.09), Se (SMD = -0.99; 95% CI: -1.55 to -0.43), and Zn
(SMD = -1.30; 95% CI: -1.75 to -0.84), while red cell levels of Zn (SMD = 1.88;
95% CI: 0.48 to 3.28) and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57) were higher. They
had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33) and Na
(SMD = 1.04; 95% CI: 0.39 to 1.69). Our findings that micronutrient levels are
different in people with DS raise the question whether these differences are
related to the different metabolic profiles, the common comorbidities or merely
reflect DS.
PMID- 28422989
TI - The lack of BTK does not impair monocytes and polymorphonuclear cells functions
in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin
replacement.
AB - The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect
monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this
study, we show that XLA patients had an increased frequency of the intermediate
monocytes subset and that BTK-deficient monocytes and PMN had a normal expression
of receptors involved in the activation and cellular responses. We demonstrate
that BTK is not required for migration, phagocytosis and the production of
reactive oxygen species (ROS) following engagement of FC gamma receptors
(FcgammaR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent
activation of oxidative burst, suggesting that oxidative burst is less dependent
by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered
also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+
mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti
inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In
monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these
functions remained efficient.
PMID- 28422990
TI - Sensory cortical response to uncertainty and low salience during recognition of
affective cues in musical intervals.
AB - Previous neuroimaging studies have shown an increased sensory cortical response
(i.e., heightened weight on sensory evidence) under higher levels of predictive
uncertainty. The signal enhancement theory proposes that attention improves the
quality of the stimulus representation, and therefore reduces uncertainty by
increasing the gain of the sensory signal. The present study employed functional
magnetic resonance imaging (fMRI) to investigate the neural correlates for
ambiguous valence inferences signaled by auditory information within an emotion
recognition paradigm. Participants categorized sound stimuli of three distinct
levels of consonance/dissonance controlled by interval content. Separate
behavioural and neuroscientific experiments were conducted. Behavioural results
revealed that, compared with the consonance condition (perfect fourths, fifths
and octaves) and the strong dissonance condition (minor/major seconds and
tritones), the intermediate dissonance condition (minor thirds) was the most
ambiguous, least salient and more cognitively demanding category (slowest
reaction times). The neuroscientific findings were consistent with a heightened
weight on sensory evidence whilst participants were evaluating intermediate
dissonances, which was reflected in an increased neural response of the right
Heschl's gyrus. The results support previous studies that have observed enhanced
precision of sensory evidence whilst participants attempted to represent and
respond to higher degrees of uncertainty, and converge with evidence showing
preferential processing of complex spectral information in the right primary
auditory cortex. These findings are discussed with respect to music-theoretical
concepts and recent Bayesian models of perception, which have proposed that
attention may heighten the weight of information coming from sensory channels to
stimulate learning about unknown predictive relationships.
PMID- 28422991
TI - Mortality is associated with inflammation, anemia, specific diseases and
treatments, and molecular markers.
AB - Lifespan is a complex trait, and longitudinal data for humans are naturally
scarce. We report the results of Cox regression and Pearson correlation analyses
using data of the Study of Health in Pomerania (SHIP), with mortality data of
1518 participants (113 of which died), over a time span of more than 10 years. We
found that in the Cox regression model based on the Bayesian information
criterion, apart from chronological age of the participant, six baseline
variables were considerably associated with higher mortality rates: smoking, mean
attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration,
albumin/creatinine ratio, treated gastritis, and medication during the last 7
days. Except for smoking, the causative contribution of these variables to
mortality was deemed inconclusive. In turn, four variables were found to be
associated with decreased mortality rates: treatment of benign prostatic
hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being
female was an undisputed causative variable, the causal role of IFG-1 was deemed
inconclusive, and the treatment effects were deemed protective to the degree that
treated subjects feature better survival than respective controls. Using Cox
modeling based on the Akaike information criterion, diabetes, mean corpuscular
hemoglobin concentration, red blood cell count and serum calcium were also
associated with mortality. The latter two, together with albumin and fibrinogen,
aligned with an"integrated albunemia" model of aging proposed recently.
PMID- 28422992
TI - The evolution of cost-efficiency in neural networks during recovery from
traumatic brain injury.
AB - A somewhat perplexing finding in the systems neuroscience has been the
observation that physical injury to neural systems may result in enhanced
functional connectivity (i.e., hyperconnectivity) relative to the typical network
response. The consequences of local or global enhancement of functional
connectivity remain uncertain and this is particularly true for the overall
metabolic cost of the network. We examine the hyperconnectivity hypothesis in a
sample of 14 individuals with TBI with data collected at approximately 3, 6, and
12 months following moderate and severe TBI. As anticipated, individuals with TBI
showed increased network strength and cost early after injury, but by one-year
post injury hyperconnectivity was more circumscribed to frontal DMN and temporal
parietal attentional control regions. Cost in these subregions was a significant
predictor of cognitive performance. Cost-efficiency analysis in the Power 264
data parcellation suggested that at 6 months post injury the network requires
higher cost connections to achieve high efficiency as compared to the network 12
months post injury. These results demonstrate that networks self-organize to re
establish connectivity while balancing cost-efficiency trade-offs.
PMID- 28422993
TI - Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin
autoinflammation.
AB - IL-1beta is a potent player in cutaneous inflammation and central for the
development of a Th17 micro-milieu in autoinflammatory diseases including
psoriasis. Its production is controlled at the transcriptional level and by
subsequent posttranslational processing via inflammatory caspases. In this study,
we detected inflammatory caspase-5 active in epidermal keratinocytes and in
psoriatic skin lesions. Further, interferon-gamma and interleukin-17A
synergistically induced caspase-5 expression in cultured keratinocytes, which was
dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases
relevant triggers for caspase-5 activity and IL-1beta production remain unknown.
Recently, extranuclear DNA has been identified as danger-signals abundant in the
psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded
(ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and
the release of IL-1beta. Further, interleukin-17A promoted caspase-5 function via
facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered
with the IL-1beta release and suppressed caspase-5 in keratinocytes and in
psoriatic skin lesions. Our data link the disease-intrinsic danger signals
psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis
providing potential therapeutic targets in Th17-mediated skin autoinflammation.
PMID- 28422994
TI - The Sheep Grimace Scale as an indicator of post-operative distress and pain in
laboratory sheep.
AB - The EU Directive 2010/63/EU changed the requirements regarding the use of
laboratory animals and raised important issues related to assessing the severity
of all procedures undertaken on laboratory animals. However, quantifiable
parameters to assess severity are rare, and improved assessment strategies need
to be developed. Hence, a Sheep Grimace Scale (SGS) was herein established by
observing and interpreting sheep facial expressions as a consequence of pain and
distress following unilateral tibia osteotomy. The animals were clinically
investigated and scored five days before surgery and at 1, 3, 7, 10, 14 and 17
days afterwards. Additionally, cortisol levels in the saliva of the sheep were
determined at the respective time points. For the SGS, video recording was
performed, and pictures of the sheep were randomized and scored by blinded
observers. Osteotomy in sheep resulted in an increased clinical severity score
from days 1 to 17 post-surgery and elevated salivary cortisol levels one day post
surgery. An analysis of facial expressions revealed a significantly increased SGS
on the day of surgery until day 3 post-surgery; this elevated level was sustained
until day 17. Clinical severity and SGS scores correlated positively with a
Pearson's correlation coefficient of 0.47. Further investigations regarding the
applicability of the SGS revealed a high inter-observer reliability with an
intraclass correlation coefficient of 0.92 and an accuracy of 68.2%. In
conclusion, the SGS represents a valuable approach for severity assessment that
may help support and refine a widely used welfare assessment for sheep during
experimental procedures, thereby meeting legislation requirements and minimizing
the occurrence of unrecognized distress in animal experimentation.
PMID- 28422995
TI - Characterization of rotavirus infection in children with acute gastroenteritis in
Bengo province, Northwestern Angola, prior to vaccine introduction.
AB - BACKGROUND: Rotavirus group A (RVA) is considered the leading cause of pediatric
diarrhea, responsible for the high burden of diarrheal diseases in sub-Saharan
Africa. Despite recent studies, the existent data are scarce for some African
countries like Angola, a country with one of the highest RVA-related death
estimates. The aim of this study was to determine the RVA detection rate and
circulating genotypes in children less than five years of age with acute
gastroenteritis attended at the Bengo General Hospital in Caxito, Bengo province,
Angola, before vaccine introduction. METHODS: Between September 2012 and December
2013, 342 fecal specimens were collected from children enrolled. Positive samples
for RVA by immunochromatographic rapid test were G and P-typed by hemi-nested
type-specific multiplex PCR, and subgrouped for the VP6 gene. VP4 and VP7 genes
from a subset of samples were sequenced for phylogenetic analysis. RESULTS:
During the study period, a high RVA detection rate was registered (25.1%,
86/342). The age group most affected by RVA infection includes children under 6
months of age (p<0.01). Vomiting was highly associated with RVA infection (72.1%;
p<0.001). From the 86 RVA-positive samples, 72 (83.7%) were genotyped. The most
prevalent genotype was G1P[8] (34/72; 47.2%), followed by the uncommon G1P[6]
(21/72; 29.2%), and G2P[4] (9/72; 12.5%). Only two G-types were found: G1 (60/72;
83.3%) and G2 (11/72; 15.3%). Among the P-genotypes, P[8] was the most prevalent
(34/72; 47.2%), followed by P[6] (22/72; 30.6%) and P[4] (9/72; 12.5%). In the
phylogenetic trees, the identified G and P-types clustered tightly together and
with reference sequences in specific monophyletic groups, with highly significant
bootstrap values (>=92%). CONCLUSION: This pre-vaccination study revealed, for
the first time for Bengo province (Angola), the RVA genotype profile, including
phylogenetic relationships, and a high RVA detection rate, supporting the
immediate introduction of a RVA vaccine in the national immunization programme.
PMID- 28422996
TI - Overexpression of an EaZIP gene devoid of transit peptide sequence induced leaf
variegation in tobacco.
AB - Leaf variegation is an ornamental trait that is not only biologically but also
economically important. In our previous study, a Mg-protoporphyrin IX monomethyl
ester cyclase homologue, EaZIP (Epipremnum aureum leucine zipper) was found to be
associated with leaf variegation in Epipremnum aureum (Linden & Andre) G.S.
Bunting. The protein product of this nuclear-encoded gene is targeted back to
chloroplast involving in chlorophyll biosynthesis. Based on a web-based homology
analysis, the EaZIP was found to lack a chloroplast transit peptide (cTP)
sequence. In the present study, we tested if overexpression of the EaZIP cDNA
with or without the cTP sequence could affect leaf variegation. Transgenic
tobacco plants overexpressing EaZIP genes with (EaZIPwcTP) and without
(EaZIPwocTP) cTP sequence were generated. Many plant lines harboring EaZIPwocTP
showed variegated leaves, while none of the plant lines with EaZIPwcTP produced
such a phenotype. Molecular analysis of T0 plants and selfed T1 progeny, as well
as observations of tagged marker GFP (green fluorescent protein) did not show any
other difference in patterns of gene integrity and expression. Results from this
study indicate that transgenic approach for expressing EaZIPwocTP could be a
novel method of generating variegated plants even through the underlying
mechanisms remain to be elucidated.
PMID- 28422998
TI - Reducing DNA context dependence in bacterial promoters.
AB - Variation in the DNA sequence upstream of bacterial promoters is known to affect
the expression levels of the products they regulate, sometimes dramatically.
While neutral synthetic insulator sequences have been found to buffer promoters
from upstream DNA context, there are no established methods for designing
effective insulator sequences with predictable effects on expression levels. We
address this problem with Degenerate Insulation Screening (DIS), a novel method
based on a randomized 36-nucleotide insulator library and a simple, high
throughput, flow-cytometry-based screen that randomly samples from a library of
436 potential insulated promoters. The results of this screen can then be
compared against a reference uninsulated device to select a set of insulated
promoters providing a precise level of expression. We verify this method by
insulating the constitutive, inducible, and repressible promotors of a four
transcriptional-unit inverter (NOT-gate) circuit, finding both that order
dependence is largely eliminated by insulation and that circuit performance is
also significantly improved, with a 5.8-fold mean improvement in on/off ratio.
PMID- 28422997
TI - Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of
neuroblastoma cells.
AB - Nuclear lamins support the nuclear envelope and provide anchorage sites for
chromatin. They are involved in DNA synthesis, transcription, and replication. It
has previously been reported that the lack of Lamin A/C expression in lymphoma
and leukaemia is due to CpG island promoter hypermethylation. Here, we provide
evidence that Lamin A/C is silenced via this mechanism in a subset of
neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a
demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth
kinetics and impaired migration, invasion, and anchorage-independent cell growth.
Cytoskeletal restructuring was also induced. In addition, the introduction of
lamin Delta50, known as Progerin, caused senescence in these neuroblastoma cells.
These cells were stiffer and developed a cytoskeletal structure that differed
from that observed upon Lamin A/C introduction. Of relevance, short hairpin RNA
Lamin A/C depletion in unmethylated neuroblastoma cells enhanced the
aforementioned tumour properties. A cytoskeletal structure similar to that
observed in methylated cells was induced. Furthermore, atomic force microscopy
revealed that Lamin A/C knockdown decreased cellular stiffness in the lamellar
region. Finally, the bioinformatic analysis of a set of methylation arrays of
neuroblastoma primary tumours showed that a group of patients (around 3%) gives a
methylation signal in some of the CpG sites located within the Lamin A/C promoter
region analysed by bisulphite sequencing PCR. These findings highlight the
importance of Lamin A/C epigenetic inactivation for a subset of neuroblastomas,
leading to enhanced tumour properties and cytoskeletal changes. Additionally,
these findings may have treatment implications because tumour cells lacking Lamin
A/C exhibit more aggressive behaviour.
PMID- 28422999
TI - Zooming in: From spatially extended traveling waves to localized structures: The
case of the Sine-Gordon equation in (1+3) dimensions.
AB - The Sine-Gordon equation in (1+3) dimensions has N-traveling front ("kink",
"domain wall")- solutions for all N >= 1. A nonlinear functional of the solution,
which vanishes on a single-front, maps multi-front solutions onto sets of
infinitely long, but laterally bounded, rods, which move in space. Each rod is
localized in the vicinity of the intersection of two Sine-Gordon fronts. The rod
systems are solutions of the linear wave equation, driven by a term that is
constructed out of Sine-Gordon fronts. An additional linear operation maps multi
rod systems onto sets of blobs. Each blob is localized in the vicinity of rod
intersection, and moves in space. The blob systems are solutions of the linear
wave equation, driven by a term that is also constructed out of Sine-Gordon
fronts. The temporal evolution of multi-blob solutions mimics elastic collisions
of systems of spatially extended particles.
PMID- 28423000
TI - Inbreeding and selection shape genomic diversity in captive populations:
Implications for the conservation of endangered species.
AB - Captive breeding programs are often initiated to prevent species extinction until
reintroduction into the wild can occur. However, the evolution of captive
populations via inbreeding, drift, and selection can impair fitness, compromising
reintroduction programs. To better understand the evolutionary response of
species bred in captivity, we used nearly 5500 single nucleotide polymorphisms
(SNPs) in populations of white-footed mice (Peromyscus leucopus) to measure the
impact of breeding regimes on genomic diversity. We bred mice in captivity for 20
generations using two replicates of three protocols: random mating (RAN),
selection for docile behaviors (DOC), and minimizing mean kinship (MK). The MK
protocol most effectively retained genomic diversity and reduced the effects of
selection. Additionally, genomic diversity was significantly related to fitness,
as assessed with pedigrees and SNPs supported with genomic sequence data. Because
captive-born individuals are often less fit in wild settings compared to wild
born individuals, captive-estimated fitness correlations likely underestimate the
effects in wild populations. Therefore, minimizing inbreeding and selection in
captive populations is critical to increasing the probability of releasing fit
individuals into the wild.
PMID- 28423001
TI - Pre-hatching embryo-dependent and -independent programming of endometrial
function in cattle.
AB - The bovine pre-implantation embryo secretes bioactive molecules from early
development stages, but effects on endometrial function are reported to start
only after elongation. Here, we interrogated spatially defined regions of the
endometrium transcriptome for responses to a day 7 embryo in vivo. We hypothesize
that exposure to an embryo changes the abundance of specific transcripts in the
cranial region of the pregnant uterine horn. Endometrium was collected from the
uterotubal junction (UTJ), anterior (IA), medial (IM) and posterior (IP) regions
of the uterine horn ipsilateral to the CL 7 days after estrus from sham
inseminated (Con) or artificially inseminated, confirmed pregnant (Preg) cows.
Abundance of 86 transcripts was evaluated by qPCR using a microfluidic platform.
Abundance of 12 transcripts was modulated in the Preg endometrium, including
classical interferon-stimulated genes (ISG15, MX1, MX2 and OAS1Y), prostaglandin
biosynthesis genes (PTGES, HPGD and AKR1C4), water channel (AQP4) and a solute
transporter (SLC1A4) and this was in the UTJ and IA mainly. Additionally, for 71
transcripts, abundance varied according to region of the reproductive tract.
Regulation included downregulation of genes associated with proliferation (IGF1,
IGF2, IGF1R and IGF2R) and extracellular matrix remodeling (MMP14, MMP19 and
MMP2) and upregulation of anti-adhesive genes (MUC1) in the cranial regions of
uterine horn. Physical proximity to the embryo provides paracrine regulation of
endometrial function. Embryo-independent regulation of the endometrial
transcriptome may support subsequent stages of embryo development, such as
elongation and implantation. We speculate that successful early embryo-dependent
and -independent programming fine-tune endometrial functions that are important
for maintenance of pregnancy in cattle.
PMID- 28423002
TI - Human SR-BII mediates SAA uptake and contributes to SAA pro-inflammatory
signaling in vitro and in vivo.
AB - Serum amyloid A (SAA) is an acute phase protein with cytokine-like and
chemotactic properties, that is markedly up-regulated during various inflammatory
conditions. Several receptors, including FPRL-1, TLR2, TLR4, RAGE, class B
scavenger receptors, SR-BI and CD36, have been identified as SAA receptors. This
study provides new evidence that SR-BII, splice variant of SR-BI, could function
as an SAA receptor mediating its uptake and pro-inflammatory signaling. The
uptake of Alexa Fluor488 SAA was markedly (~3 fold) increased in hSR-BII
expressing HeLa cells when compared with mock-transfected cells. The levels of
SAA-induced interleukin-8 secretion by hSR-BII-expressing HEK293 cells were also
significantly (~3-3.5 fold) higher than those detected in control cells.
Moderately enhanced levels of phosphorylation of all three mitogen-activated
protein kinases, ERK1/2, and p38 and JNK, were observed in hSR-BII-expressing
cells following SAA stimulation when compared with control wild type cells.
Transgenic mice with pLiv-11-directed liver/kidney overexpression of hSR-BI or
hSR-BII were used to assess the in vivo role of each receptor in SAA-induced pro
inflammatory response in these organs. Six hours after intraperitoneal SAA
injection both groups of transgenic mice demonstrated markedly higher (~2-5-fold)
expression levels of inflammatory mediators in the liver and kidney compared to
wild type mice. Histological examinations of hepatic and renal tissue from SAA
treated mice revealed moderate level of damage in the liver of both transgenic
but not in the wild type mice. Activities of plasma transaminases, biomarkers of
liver injury, were also moderately higher in hSR-B transgenic mice when compared
to wild type mice. Our findings identify hSR-BII as a functional SAA receptor
that mediates SAA uptake and contributes to its pro-inflammatory signaling via
the MAPKs-mediated signaling pathways.
PMID- 28423003
TI - HacDivSel: Two new methods (haplotype-based and outlier-based) for the detection
of divergent selection in pairs of populations.
AB - The detection of genomic regions involved in local adaptation is an important
topic in current population genetics. There are several detection strategies
available depending on the kind of genetic and demographic information at hand. A
common drawback is the high risk of false positives. In this study we introduce
two complementary methods for the detection of divergent selection from
populations connected by migration. Both methods have been developed with the aim
of being robust to false positives. The first method combines haplotype
information with inter-population differentiation (FST). Evidence of divergent
selection is concluded only when both the haplotype pattern and the FST value
support it. The second method is developed for independently segregating markers
i.e. there is no haplotype information. In this case, the power to detect
selection is attained by developing a new outlier test based on detecting a
bimodal distribution. The test computes the FST outliers and then assumes that
those of interest would have a different mode. We demonstrate the utility of the
two methods through simulations and the analysis of real data. The simulation
results showed power ranging from 60-95% in several of the scenarios whilst the
false positive rate was controlled below the nominal level. The analysis of real
samples consisted of phased data from the HapMap project and unphased data from
intertidal marine snail ecotypes. The results illustrate that the proposed
methods could be useful for detecting locally adapted polymorphisms. The software
HacDivSel implements the methods explained in this manuscript.
PMID- 28423004
TI - Variations in the interaction of human defensins with Escherichia coli: Possible
implications in bacterial killing.
AB - Human alpha and beta-defensins are cationic antimicrobial peptides characterized
by three disulfide bonds with a triple stranded beta-sheet motif. It is presumed
that interaction with the bacterial cell surface and membrane permeabilization by
defensins is an important step in the killing process. In this study, we have
compared interactions of three human alpha-defensins HNP3, HNP4, HD5 and human
beta-defensins HBD1-4 that are active against Escherichia coli, with its cell
surface and inner membrane as well as negatively charged model membranes. We have
also included the inactive alpha-defensin HD6 in the study. Among the alpha
defensins, HNP4, HD5 and HD6 were more effective in increasing the zeta potential
as compared to HNP3. Among the beta-defensins, HBD1 was the least effective in
increasing the zeta potential. The zeta potential modulation data indicate
variations in the surface charge neutralizing ability of alpha- and beta
defensins. Comparison of E. coli inner membrane and model membrane permeabilizing
abilities indicated that HD5, HD6 and HBD1 do not permeabilize membranes.
Although HBD4 does not permeabilize model membranes, considerable damage to the
inner membrane of E. coli is observed. Our data indicate that mammalian defensins
do not kill E. coli by a simple mechanism involving membrane permeabilization
though their antibacterial potencies are very similar.
PMID- 28423005
TI - An archosauromorph dominated ichnoassemblage in fluvial settings from the late
Early Triassic of the Catalan Pyrenees (NE Iberian Peninsula).
AB - The vertebrate recovery after the end-Permian mass extinction can be approached
through the ichnological record, which is much more abundant than body fossils.
The late Olenekian (Early Triassic) tetrapod ichnoassemblage of the Catalan
Pyrenean Basin is the most complete and diverse of this age from Western Tethys.
This extensional basin, composed of several depocenters, was formed in the latest
phases of the Variscan orogeny (Pangea breakup) and was infilled by braided and
meandering fluvial systems of the red-beds Buntsandstein facies. Abundant and
diverse tetrapod ichnites are recorded in these facies, including Prorotodactylus
mesaxonichnus isp. nov. (tracks possibly produced by euparkeriids), cf.
Rotodactylus, at least two large chirotheriid morphotypes (archosauriform
trackmakers), Rhynchosauroides cf. schochardti, two other undetermined
Rhynchosauroides forms, an undetermined Morphotype A (archosauromorph
trackmakers) and two types of Characichnos isp. (swimming traces, here associated
to archosauromorph trackmakers). The Pyrenean ichnoassemblage suggests a
relatively homogeneous ichnofaunal composition through the late Early Triassic of
Central Pangea, characterized by the presence of Prorotodactylus and
Rotodactylus. Small archosauromorph tracks dominate and present a wide
distribution through the different fluviatile facies of the Triassic Pyrenean
Basin, with large archosaurian footprints being present in a lesser degree.
Archosauromorphs radiated and diversified through the Triassic vertebrate
recovery, which ultimately lead to the archosaur and dinosaur dominance of the
Mesozoic.
PMID- 28423006
TI - Transcriptome and proteome responses in RNAlater preserved tissue of Arabidopsis
thaliana.
AB - Tissue preservation is a minimal requirement for the success of plant RNA and
protein expression studies. The standard of snap-freezing in liquid nitrogen is
not always practical or possible. RNAlater, a concentrated solution of ammonium
and cesium sulfates, has become a standard preservative in the absence of liquid
nitrogen. Here, we demonstrate the effectiveness of RNAlater in preserving both
RNA and proteins in Arabidopsis thaliana tissues for use in RNAseq and LC-MS/MS
analysis of proteins. While successful in preserving plant material, a
transcriptomic and proteomic response is evident. Specifically, 5770 gene
transcripts, 84 soluble proteins, and 120 membrane-bound proteins were found to
be differentially expressed at a log-fold change of +/-1 (P <= 0.05). This
response is mirrored in the abundance of post-translational modifications, with
23 of the 108 (21.3%) phosphorylated proteins showing altered abundance at a log
fold change of +/-1 (P <= 0.05). While RNAlater is effective in preserving
biological information, our findings warrant caution in its use for
transcriptomic and proteomic experiments.
PMID- 28423007
TI - Recombinants from the crosses between amphidiploid and cultivated peanut (Arachis
hypogaea) for pest-resistance breeding programs.
AB - Peanut is a major oilseed crop worldwide. In the Brazilian peanut production,
silvering thrips and red necked peanut worm are the most threatening pests.
Resistant varieties are considered an alternative to pest control. Many wild
diploid Arachis species have shown resistance to these pests, and these can be
used in peanut breeding by obtaining hybrid of A and B genomes and subsequent
polyploidization with colchicine, resulting in an AABB amphidiploid. This
amphidiploid can be crossed with cultivated peanut (AABB) to provide genes of
interest to the cultivar. In this study, the sterile diploid hybrids from A.
magna V 13751 and A. kempff-mercadoi V 13250 were treated with colchicine for
polyploidization, and the amphidiploids were crossed with A. hypogaea cv. IAC OL
4 to initiate the introgression of the wild genes into the cultivated peanut. The
confirmation of the hybridity of the progenies was obtained by: (1) reproductive
characterization through viability of pollen, (2) molecular characterization
using microsatellite markers and (3) morphological characterization using 61
morphological traits with principal component analysis. The diploid hybrid
individual was polyploidized, generating the amphidiploid An 13 (A. magna V 13751
x A. kempff-mercadoi V 13250)4x. Four F1 hybrid plants were obtained from IAC OL
4 * An 13, and 51 F2 seeds were obtained from these F1 plants. Using
reproductive, molecular and morphological characterizations, it was possible to
distinguish hybrid plants from selfed plants. In the cross between A. hypogaea
and the amphidiploid, as the two parents are polyploid, the hybrid progeny and
selves had the viability of the pollen grains as high as the parents. This fact
turns the use of reproductive characteristics impossible for discriminating, in
this case, the hybrid individuals from selfing. The hybrids between A. hypogaea
and An 13 will be used in breeding programs seeking pest resistance, being
subjected to successive backcrosses until recovering all traits of interest of A.
hypogaea, keeping the pest resistance.
PMID- 28423008
TI - Perirenal fat thickness measured with computed tomography is a reliable estimate
of perirenal fat mass.
AB - Deposition of perirenal adipose tissue has been associated with adverse renal and
cardiovascular events. We compared various methods to measure perirenal adipose
tissue using computerized tomography (CT)-scan and performed correlations with
anthropometric measures associated with renal and cardiovascular events.
Voluntary overweight and obese subjects undergoing a CT-scan for diagnostic
purposes were included in the study. Perirenal adipose tissue volume, adipose
tissue area of the renal sinus and perirenal fat thickness were manually measured
bilaterally. The intra- and inter-observer coefficient correlations and the
correlation between the diverse measures of renal adipose tissue, subcutaneous
(SC-)fat and anthropometrics measures were analyzed using Pearson's correlation
tests. The forty included patients (24 men, 16 women) had a mean age of 57.6 +/-
18.1 years and a mean body mass index of 28.9 +/- 2.9 kg/m2. Despite comparable
waist circumference, women had a greater SC-fat thickness compared to men, and
therefore a smaller amount of visceral fat, as well as smaller perirenal fat
volumes. Perirenal fat thickness was better correlated with perirenal fat volume
than adipose area of the renal sinus (p <0.02). The adipose area of the renal
sinus did not correlate with any anthropometric measures. In women, perirenal fat
volume and thickness showed a negative correlation with SC-fat thickness and no
correlation with waist circumference. In men, perirenal fat volume and thickness
showed a positive correlation with waist circumference and no correlation with
subcutaneous fat thickness. In conclusion, perirenal fat thickness measured with
CT-scan at the level of the renal veins is a simple and reliable estimate of
perirenal fat volume, that correlated negatively with SC-fat in women and
positively with waist circumference in men. The adipose area of the renal sinus
did not correlate with any anthropometric measure.
PMID- 28423009
TI - Correction: Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2
Concentrations Are Related to Renal Function in Two Population-Based Cohorts.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166492.].
PMID- 28423010
TI - Correction: The H3K27 demethylase, Utx, regulates adipogenesis in a
differentiation stage-dependent manner.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173713.].
PMID- 28423011
TI - The range of the mange: Spatiotemporal patterns of sarcoptic mange in red foxes
(Vulpes vulpes) as revealed by camera trapping.
AB - Sarcoptic mange is a widely distributed disease that affects numerous mammalian
species. We used camera traps to investigate the apparent prevalence and
spatiotemporal dynamics of sarcoptic mange in a red fox population in
southeastern Norway. We monitored red foxes for five years using 305 camera traps
distributed across an 18000 km2 area. A total of 6581 fox events were examined to
visually identify mange compatible lesions. We investigated factors associated
with the occurrence of mange by using logistic models within a Bayesian
framework, whereas the spatiotemporal dynamics of the disease were analysed with
space-time scan statistics. The apparent prevalence of the disease fluctuated
over the study period with a mean of 3.15% and credible interval [1.25, 6.37],
and our best logistic model explaining the presence of red foxes with mange
compatible lesions included time since the beginning of the study and the
interaction between distance to settlement and season as explanatory variables.
The scan analyses detected several potential clusters of the disease that varied
in persistence and size, and the locations in the cluster with the highest
probability were closer to human settlements than the other survey locations. Our
results indicate that red foxes in an advanced stage of the disease are most
likely found closer to human settlements during periods of low wild prey
availability (winter). We discuss different potential causes. Furthermore, the
disease appears to follow a pattern of small localized outbreaks rather than
sporadic isolated events.
PMID- 28423012
TI - 15-hydroxyprostaglandin dehydrogenase (15-PGDH) prevents lipopolysaccharide (LPS)
induced acute liver injury.
AB - The NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the
oxidation of the 15(S)-hydroxyl group of prostaglandin E2 (PGE2), converting the
pro-inflammatory PGE2 to the anti-inflammatory 15-keto-PGE2 (an endogenous ligand
for peroxisome proliferator-activated receptor-gamma [PPAR-gamma]). To evaluate
the significance of 15-PGDH/15-keto-PGE2 cascade in liver inflammation and tissue
injury, we generated transgenic mice with targeted expression of 15-PGDH in the
liver (15-PGDH Tg) and the animals were subjected to lipopolysaccharide
(LPS)/Galactosamine (GalN)-induced acute liver inflammation and injury. Compared
to the wild type mice, the 15-PGDH Tg mice showed lower levels of alanine
aminotransferase (ALT) and aspartate aminotransferase (AST), less liver tissue
damage, less hepatic apoptosis/necrosis, less macrophage activation, and lower
inflammatory cytokine production. In cultured Kupffer cells, treatment with 15
keto-PGE2 or the conditioned medium (CM) from 15-PGDH Tg hepatocyes inhibited LPS
induced cytokine production, in vitro. Both 15-keto-PGE2 and the CM from15-PGDH
Tg hepatocyes also up-regulated the expression of PPAR-gamma downstream genes in
Kupffer cells. In cultured hepatocytes, 15-keto-PGE2 treatment or 15-PGDH
overexpression did not influence TNF-alpha-induced hepatocyte apoptosis. These
findings suggest that 15-PGDH protects against LPS/GalN-induced liver injury and
the effect is mediated via 15-keto-PGE2, which activates PPAR-gamma in Kupffer
cells and thus inhibits their ability to produce inflammatory cytokines.
Accordingly, we observed that the PPAR-gamma antagonist, GW9662, reversed the
effect of 15-keto-PGE2 in Kupffer cell in vitro and restored the susceptibility
of 15-PGDH Tg mice to LPS/GalN-induced acute liver injury in vivo. Collectively,
our findings suggest that 15-PGDH-derived 15-keto-PGE2 from hepatocytes is able
to activate PPAR-gamma and inhibit inflammatory cytokine production in Kupffer
cells and that this paracrine mechanism negatively regulates LPS-induced necro
inflammatory response in the liver. Therefore, induction of 15-PGDH expression or
utilization of 15-keto-PGE2 analogue may have therapeutic benefits for the
treatment of endotoxin-associated liver inflammation/injury.
PMID- 28423014
TI - Initial systemic inflammatory state perturbs exercise training adaptations in
elite Taekwondo athletes.
AB - PURPOSE: This study examined ten-week TKD-specific training effects on aerobic
capacity, body composition, hormone responses and hematological parameters in
elite TKD athletes with varied initial inflammatory states. METHODS: Twenty-two
elite college TKD athletes were divided into two groups according to their
initial neutrophils-to-lymphocytes ratio (NLR) values: Low NLR (N = 11, 9M/2F,
age: 21.6 +/- 1.0 yrs; NLR: 1.3 +/- 0.2) and High NLR (N = 11, 8M/3F, age: 22.0
+/- 0.7 yrs, NLR: 2.5 +/- 1.3), and participated in a 10-week TKD-specific
training program. Aerobic capacity, body composition, hormonal responses and
hematological parameters were measured at baseline and 10-weeks after TKD
training. RESULTS: VO2max and shuttle run distance were significantly increased
in both groups after training. However, the degree of improvement was greater in
the Low NLR group than in the High NLR group. After 10-weeks of exercise
training, the High NLR group presented markedly higher fat mass percentage and
visceral fat area and significantly lowers DHEA-S to cortisol ratio (D/C ratio)
than the Low NRL group. The post-training NLR was negatively correlated with the
D/C ratio. Neutrophil counts and NLR were still significantly higher in the High
NLR group after training. CONCLUSIONS: This study provides new evidence that
young elite TKD athletes with slightly high baseline systemic inflammatory state
appear to perturb adaptations to exercise training.
PMID- 28423013
TI - Mapping the co-localization of the circadian proteins PER2 and BMAL1 with
enkephalin and substance P throughout the rodent forebrain.
AB - Despite rhythmic expression of clock genes being found throughout the central
nervous system, very little is known about their function outside of the
suprachiasmatic nucleus. Determining the pattern of clock gene expression across
neuronal subpopulations is a key step in understanding their regulation and how
they may influence the functions of various brain structures. Using
immunofluorescence and confocal microscopy, we quantified the co-expression of
the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and
Enkephalin (Enk), expressed in distinct neuronal populations throughout the
forebrain. Regions examined included the limbic forebrain (dorsal striatum,
nucleus accumbens, amygdala, stria terminalis), thalamus medial habenula of the
thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the
olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in
nearly all neurons (~90%), and PER2 was expressed in a slightly lower proportion
of cells. There was no specific correlation to SubP- or Enk- expressing
subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were
expressed in a much smaller percentage of cells, and Enk was rarely found in the
same cells that expressed the clock proteins (SubP was undetectable). These
results indicate that clock genes are not unique to specific cell types, and
further studies will be required to determine the factors that contribute to the
regulation of clock gene expression throughout the brain.
PMID- 28423015
TI - Correction: 16 Weeks of Progressive Barefoot Running Training Changes Impact
Force and Muscle Activation in Habitual Shod Runners.
AB - [This corrects the article DOI: 10.1371/journal.pone.0167234.].
PMID- 28423016
TI - Evaluating the utility of two gestural discomfort evaluation methods.
AB - Evaluating physical discomfort of designed gestures is important for creating
safe and usable gesture-based interaction systems; yet, gestural discomfort
evaluation has not been extensively studied in HCI, and few evaluation methods
seem currently available whose utility has been experimentally confirmed. To
address this, this study empirically demonstrated the utility of the subjective
rating method after a small number of gesture repetitions (a maximum of four
repetitions) in evaluating designed gestures in terms of physical discomfort
resulting from prolonged, repetitive gesture use. The subjective rating method
has been widely used in previous gesture studies but without empirical evidence
on its utility. This study also proposed a gesture discomfort evaluation method
based on an existing ergonomics posture evaluation tool (Rapid Upper Limb
Assessment) and demonstrated its utility in evaluating designed gestures in terms
of physical discomfort resulting from prolonged, repetitive gesture use. Rapid
Upper Limb Assessment is an ergonomics postural analysis tool that quantifies the
work-related musculoskeletal disorders risks for manual tasks, and has been
hypothesized to be capable of correctly determining discomfort resulting from
prolonged, repetitive gesture use. The two methods were evaluated through
comparisons against a baseline method involving discomfort rating after actual
prolonged, repetitive gesture use. Correlation analyses indicated that both
methods were in good agreement with the baseline. The methods proposed in this
study seem useful for predicting discomfort resulting from prolonged, repetitive
gesture use, and are expected to help interaction designers create safe and
usable gesture-based interaction systems.
PMID- 28423017
TI - Auxotonic to isometric contraction transitioning in a beating heart causes myosin
step-size to down shift.
AB - Myosin motors in cardiac ventriculum convert ATP free energy to the work of
moving blood volume under pressure. The actin bound motor cyclically rotates its
lever-arm/light-chain complex linking motor generated torque to the myosin
filament backbone and translating actin against resisting force. Previous
research showed that the unloaded in vitro motor is described with high precision
by single molecule mechanical characteristics including unitary step-sizes of
approximately 3, 5, and 8 nm and their relative step-frequencies of approximately
13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin
essential light chain (ELC) N-terminus actin binding. Step-size and step
frequency quantitation specifies in vitro motor function including duty-ratio,
power, and strain sensitivity metrics. In vivo, motors integrated into the muscle
sarcomere form the more complex and hierarchically functioning muscle machine.
The goal of the research reported here is to measure single myosin step-size and
step-frequency in vivo to assess how tissue integration impacts motor function. A
photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in
the beating heart of a live zebrafish embryo. Detected single GFP emission
reports time-resolved myosin lever-arm orientation interpreted as step-size and
step-frequency providing single myosin mechanical characteristics over the active
cycle. Following step-frequency of cardiac ventriculum myosin transitioning from
low to high force in relaxed to auxotonic to isometric contraction phases
indicates that the imposition of resisting force during contraction causes the
motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in
the near-isometric phase. At peak force, the ATP initiated actomyosin
dissociation is the predominant strain inhibited transition in the native myosin
contraction cycle. The proposed model for motor down-shifting and strain sensing
involves ELC N-terminus actin binding. Overall, the approach is a unique bottom
up single molecule mechanical characterization of a hierarchically functional
native muscle myosin.
PMID- 28423018
TI - Comprehensive analysis of phospholipids and glycolipids in the opportunistic
pathogen Enterococcus faecalis.
AB - Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium
that causes a significant number of antibiotic-resistant infections in
hospitalized patients. The development of antibiotic resistance in hospital
associated pathogens is a formidable public health threat. In E. faecalis and
other Gram-positive pathogens, correlations exist between lipid composition and
antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is
accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple
peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a
trans-esterification reaction, providing resistance to cationic antimicrobial
peptides. Unlike previous studies that relied on thin layer chromatography and
spectrophotometry, we have performed liquid chromatography-tandem mass
spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and
quantified the phospholipids through multiple reaction monitoring (MRM). In the
daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl
PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols
(GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4
triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary
during growth of E. faecalis in vitro. We also show that two daptomycin-resistant
(DapR) strains of E. faecalis have substantially lower levels of PG and LPG
levels. Since LPG levels in these strains are lower, daptomycin resistance is
likely due to the reduction in PG. This lipidome map is the first comprehensive
analysis of membrane phospholipids and glycolipids in the important human
pathogen E. faecalis, for which antimicrobial resistance and altered lipid
homeostasis have been intimately linked.
PMID- 28423019
TI - Design, synthesis and structure-activity relationship study of wollamide B; a new
potential anti TB agent.
AB - Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits
activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 MUM). Aiming to
define its structural activity relationship (SAR), optimizing potency and
pharmacokinetic properties, libraries of analogues were synthesized following a
standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial
activities of wollamide B and all the synthesized analogues were tested against
Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and
pharmacokinetic (ADME) profiling was done for the synthesized compounds to
evaluate their drug likeness. Among the 25 synthesized wollamides five of them
showed potent activities with MICs <= 3.1 MUM and found to be nontoxic against
human HepG2 cells up to 100 MUM. The results of the in vitro ADME profiling
revealed the remarkable plasma stability and very good aqueous solubility of the
class in general while the metabolic stability was found to be moderate to low.
Of particular note, compounds 7c (MIC = 1.1 MUM) and 13c (0.6 MUM) that exhibited
good balance of antimycobacterial activity vs. optimal pharmacokinetic properties
could be used as a new lead for further development.
PMID- 28423020
TI - Refractive error change and vision improvement in moderate to severe hyperopic
amblyopia after spectacle correction: Restarting the emmetropization process?
AB - PURPOSE: The aims of the study were to develop guidelines for prescribing
spectacles for patients with moderate to severe hyperopic amblyopia and to
demonstrate how emmetropization progresses. METHODS: Children with hyperopic
amblyopia who had a spherical equivalent of >= +4.0 diopters (D) or more were
included, while those who had astigmatism of > 2.0 D or anisometropia of > 2.0 D
were excluded. The patients were divided into a full correction group and an
under-correction group according to the amount of hyperopia correction applied.
The under-correction group was further subdivided into a fixed under-correction
group and a post-cycloplegic refraction (PCR) under-correction group. The
duration of amblyopia treatment and changes in initial hyperopia were compared
between the groups. RESULTS: In total, 76 eyes of 38 patients were analyzed in
this study. The full correction group and under-correction group were subjected
to 5.5 months and 5.9 months of amblyopia treatment, respectively (P = 0.570).
However, the PCR under-correction group showed more rapid improvement (2.9
months; P = 0.001). In the under-correction group, initial hyperopia was
decreased by -0.28 D and -0.49 D at 6 months and 12 months, respectively, after
initial cycloplegic refraction. Moreover, the amount of hyperopia under
correction was correlated with the amount of hyperopia reduction (P = 0.010).
CONCLUSION: The under-correction of moderate to severe hyperopic amblyopia has
beneficial effects for treating amblyopia and activating emmetropization. PCR
under-correction can more rapidly improve visual acuity, while both fixed under
correction and PCR under-correction can induce emmetropization and effectively
reduce initial hyperopia.
PMID- 28423021
TI - Trait impulsivity components correlate differently with proactive and reactive
control.
AB - The relationship between impulsivity and cognitive control is still unknown. We
hypothesized that trait impulsivity would differentially correlate with specific
cognitive control processes. Trait impulsivity was measured by the Barratt
Impulsiveness Scale, which assesses motor, attention, and non-planning
impulsiveness components. Cognitive control was measured by a hybrid-designed
Stroop task, which distinguishes proactive and reactive control. Thirty-three
participants performed the Stroop task while they were scanned by functional
magnetic resonance imaging. Proactive and reactive control involved increased
activity in the fronto-parietal network, and brain activity was associated with
impulsivity scores. Specifically, higher motor impulsiveness was associated with
a larger proactive control effect in the inferior parietal lobule and a smaller
reactive control effect in the right dorsolateral prefrontal cortex (DLPFC) and
anterior cingulate contex. Higher attention impulsivity was associated with a
smaller proactive control effect in the right DLPFC. Such a correlation pattern
suggests that impulsivity trait components are attributable to different
cognitive control subsystems.
PMID- 28423022
TI - Bioactivity and structure-activity relationship of cinnamic acid esters and their
derivatives as potential antifungal agents for plant protection.
AB - A series of cinnamic acid esters and their derivatives were synthesized and
evaluated for antifungal activities in vitro against four plant pathogenic fungi
by using the mycelium growth rate method. Structure-activity relationship was
derived also. Almost all of the compounds showed some inhibition activity on each
of the fungi at 0.5 mM. Eight compounds showed the higher average activity with
average EC50 values of 17.4-28.6 MUg/mL for the fungi than kresoxim-methyl, a
commercial fungicide standard, and ten compounds were much more active than
commercial fungicide standards carbendazim against P. grisea or kresoxim-methyl
against both P. grisea and Valsa mali. Compounds C1 and C2 showed the higher
activity with average EC50 values of 17.4 and 18.5 MUg/mL and great potential for
development of new plant antifungal agents. The structure-activity relationship
analysis showed that both the substitution pattern of the phenyl ring and the
alkyl group in the alcohol moiety significantly influences the activity. There
exists complexly comprehensive effect between the substituents on the phenyl ring
and the alkyl group in the alcohol moiety on the activity. Thus, cinnamic acid
esters showed great potential the development of new antifungal agents for plant
protection due to high activity, natural compounds or natural compound framework,
simple structure, easy preparation, low-cost and environmentally friendly.
PMID- 28423023
TI - Nanoscale modifications in the early heating stages of bone are heterogeneous at
the microstructural scale.
AB - Nanoscale studies of bone provide key indicators to evidence subtle structural
changes that may occur in the biomedical, forensic and archaeological contexts.
One specific problem encountered in all those disciplines, for which the
identification of nanostructural cues could prove useful, is to properly monitor
the effect of heating on bone tissue. In particular, the mechanisms at work at
the onset of heating are still relatively unclear. Using a multiscale approach
combining Raman microspectroscopy, transmission electron microscopy (TEM),
synchrotron quantitative scanning small-angle X-ray scattering imaging (qsSAXSI)
and polarized light (PL) microscopy, we investigate the ultrastructure of
cortical bovine bone heated at temperatures < 300 degrees C, from the molecular
to the macroscopic scale. We show that, despite limited changes in crystal
structure, the mineral nanoparticles increase in thickness and become strongly
disorganized upon heating. Furthermore, while the nanostructure in distinct
anatomical quadrants appears to be statistically different, our results
demonstrate this stems from the tissue histology, i.e. from the high degree of
heterogeneity of the microstructure induced by the complex cellular processes
involved in bone tissue formation. From this study, we conclude that the analysis
of bone samples based on the structure and organization of the mineral
nanocrystals requires performing measurements at the histological level, which is
an advantageous feature of qsSAXSI. This is a critical aspect that extends to a
much broader range of questions relating to nanoscale investigations of bone,
which could also be extended to other classes of nanostructured heterogeneous
materials.
PMID- 28423024
TI - Interrelationships of VEL1 and ENV1 in light response and development in
Trichoderma reesei.
AB - Sexual development is regulated by a complex regulatory mechanism in fungi. For
Trichoderma reesei, the light response pathway was shown to impact sexual
development, particularly through the photoreceptor ENVOY. Moreover, T. reesei
communicates chemically with a potential mating partner in its vicinity, a
response which is mediated by the velvet family protein VEL1 and its impact on
secondary metabolism. We therefore studied the regulatory interactions of ENV1
and VEL1 with a focus on sexual development. Although individual mutants in both
genes are female sterile under standard crossing conditions (light-dark cycles),
an altered light regime enabled sexual development, which we found to be due to
conditional female sterility of Deltaenv1, but not Deltavel1. Phenotypes of
growth and asexual sporulation as well as regulation of the peptide pheromone
precursors of double mutants suggested that ENV1 and VEL1 balance positive and
negative regulators of these functions. Additionally, VEL1 contributed to the
strong deregulation of the pheromone system observed in env1 mutants. Female
sterility of Deltavel1 was rescued by deletion of env1 in darkness in MAT1-1,
indicating a block of sexual development by ENV1 in darkness that is balanced by
VEL1 in the wild-type. We conclude that ENV1 and VEL1 exert complementing
functions in development of T. reesei. Our results further showed that the
different developmental phenotypes of vel1/veA mutants in T. reesei and
Aspergillus nidulans are not due to the presence or function of ENV1 in the
VELVET regulatory pathway in T. reesei.
PMID- 28423025
TI - Determination of influenza B identity and potency in quadrivalent inactivated
influenza vaccines using lineage-specific monoclonal antibodies.
AB - Co-circulation of two antigenically and genetically distinct lineages of
influenza B virus, represented by prototype viruses B/Victoria/2/1987 and
B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines
that contain two influenza B antigens. The inclusion of two influenza B antigens
presents challenges for the production and regulation of inactivated quadrivalent
vaccines, including the potential for cross-reactivity of the reagents used in
identity and potency assays because of the relative close relatedness of the
hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs)
specific for the two lineages of influenza B HA were generated and characterized
and used to set-up simple identity tests that distinguish the influenza B
antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific
mAbs bound well to the HA of influenza B strains included in influenza vaccines
over a period of more than 10 years, suggesting that identity tests using such
lineage-specific mAbs would not necessarily have to be updated with every
influenza B vaccine strain change. These lineage-specific mAbs were also used in
an antibody capture ELISA format to quantify HA in vaccine samples, including
monovalent, trivalent, and quadrivalent vaccine samples from various
manufacturers. The results demonstrated correlation with HA values determined by
the traditional single radial immunodiffusion (SRID) assay. Further, the antibody
capture ELISA was able to distinguish heat-stressed vaccine from unstressed
vaccine, and was similar to the SRID in quantifying the resultant loss of
potency. These mAb reagents should be useful for further development of antibody
based alternative influenza B identity and potency assays.
PMID- 28423026
TI - The relationship between diabetes and colorectal cancer prognosis: A meta
analysis based on the cohort studies.
AB - INTRODUCTION: Though a meta-analysis reported the effect of diabetes on
colorectal prognosis in 2013, a series of large-scale long-term cohort studies
has comprehensively reported the outcome effect estimates on the relationship
between diabetes and colorectal prognosis, and their results were still
consistent. METHODS: We carried out an extensive search strategy in multiple
databases and conducted a meta-analysis on the effect of diabetes on colorectal
prognosis, based on the included 36 cohort studies, which contained 2,299,012
subjects. In order to collect more data, besides conventional methods, we used
the professional software to extract survival data from the Kaplan-Meier curves,
and analyzed both the 5-year survival rate and survival risk in overall survival,
cancer-specific survival, cardiovascular disease-specific survival, disease-free
survival, and recurrence-free survival, to comprehensively reflect the effect of
diabetes on colorectal prognosis. RESULTS: The results found that compared to
patients without diabetes, patients with diabetes will have a 5-year shorter
survival in colorectal, colon and rectal cancer, with a 18%, 19% and 16%
decreased in overall survival respectively. We also found similar results in
cancer-specific survival, cardiovascular disease-specific survival, disease-free
survival, and recurrence-free survival, but not all these results were
significant. We performed the subgroup analysis and sensitivity analysis to find
the source of heterogeneity. Their results were similar to the overall results.
CONCLUSIONS: Our meta-analysis suggested that diabetes had a negative effect on
colorectal cancer in overall survival. More studies are still needed to confirm
the relationship between diabetes and colorectal prognosis in cancer-specific
survival, cardiovascular disease-specific survival, disease-free survival, and
recurrence-free survival.
PMID- 28423027
TI - Comparison of T2*-weighted and QSM contrasts in Parkinson's disease to visualize
the STN with MRI.
AB - The subthalamic nucleus (STN) plays a crucial role in the surgical treatment of
Parkinson's disease (PD). Studies investigating optimal protocols for STN
visualization using state of the art magnetic resonance imaging (MRI) techniques
have shown that susceptibility weighted images, which display the magnetic
susceptibility distribution, yield better results than T1-weighted, T2-weighted,
and T2*-weighted contrasts. However, these findings are based on young healthy
individuals, and require validation in elderly individuals and persons suffering
from PD. Using 7T MRI, the present study set out to investigate which MRI
contrasts yielded the best results for STN visualization in 12 PD patients and
age-matched healthy controls (HC). We found that STNs were more difficult to
delineate in PD as reflected by a lower inter-rater agreement when compared to
HCs. No STN size differences were observed between the groups. Analyses of
quantitative susceptibility mapping (QSM) images showed a higher inter-rater
agreement reflected by increased Dice-coefficients. The location of the center of
mass of the STN was not affected by contrast. Overall, contrast-to-noise ratios
(CNR) were higher in QSM than in T2*-weighted images. This can at least
partially, explain the higher inter-rater agreement in QSM. The current results
indicate that the calculation of QSM contrasts contributes to an improved
visualization of the entire STN. We conclude that QSM contrast is the preferred
choice for the visualization of the STN in persons with PD as well as in aging
HC.
PMID- 28423028
TI - Four human Plasmodium species quantification using droplet digital PCR.
AB - Droplet digital polymerase chain reaction (ddPCR) is a partial PCR based on water
oil emulsion droplet technology. It is a highly sensitive method for detecting
and delineating minor alleles from complex backgrounds and provides absolute
quantification of DNA targets. The ddPCR technology has been applied for
detection of many pathogens. Here the sensitive assay utilizing ddPCR for
detection and quantification of Plasmodium species was investigated. The assay
was developed for two levels of detection, genus specific for all Plasmodium
species and for specific Plasmodium species detection. The ddPCR assay was
developed based on primers and probes specific to the Plasmodium genus 18S rRNA
gene. Using ddPCR for ultra-sensitive P. falciparum assessment, the lower level
of detection from concentrated DNA obtained from a high volume (1 mL) blood
sample was 11 parasites/mL. For species identification, in particular for samples
with mixed infections, a duplex reaction was developed for detection and
quantification P. falciparum/ P. vivax and P. malariae/ P. ovale. Amplification
of each Plasmodium species in the duplex reaction showed equal sensitivity to
singleplex single species detection. The duplex ddPCR assay had higher
sensitivity to identify minor species in 32 subpatent parasitaemia samples from
Cambodia, and performed better than real-time PCR. The ddPCR assay shows high
sensitivity to assess very low parasitaemia of all human Plasmodium species. This
provides a useful research tool for studying the role of the asymptomatic
parasite reservoir for transmission in regions aiming for malaria elimination.
PMID- 28423029
TI - Evaluating dispersal potential of an invasive fish by the use of aerobic scope
and osmoregulation capacity.
AB - Non-indigenous species (NIS) can impact marine biodiversity and ecosystem
structure and function. Once introduced into a new region, secondary dispersal is
limited by the physiology of the organism in relation to the ambient environment
and by complex interactions between a suite of ecological factors such as
presence of predators, competitors, and parasites. Early prediction of dispersal
potential and future 'area of impact' is challenging, but also a great asset in
taking appropriate management actions. Aerobic scope (AS) in fish has been linked
to various fitness-related parameters, and may be valuable in determining
dispersal potential of aquatic invasive species in novel environments. Round
goby, Neogobius melanostomus, one of the most wide-ranging invasive fish species
in Europe and North America, currently thrives in brackish and fresh water, but
its ability to survive in high salinity waters is unknown to date. We show that
AS in round goby is reduced by 30% and blood plasma osmolality increased
(indicating reduced capacity for osmoregulation) at salinities approaching
oceanic conditions, following slow ramping (5 PSU per week) and subsequent long
term acclimation to salinities ranging between 0 and 30 PSU (8 days at final
treatment salinities before blood plasma osmolality measurements, 12-20
additional days before respirometry). Survival was also reduced at the highest
salinities yet a significant proportion (61%) of the fish survived at 30 PSU.
Reduced physiological performance at the highest salinities may affect growth and
competitive ability under oceanic conditions, but to what extent reduced AS and
osmoregulatory capacity will slow the current 30 km year-1 rate of advance of the
species through the steep salinity gradient from the brackish Baltic Sea and into
the oceanic North Sea remains speculative. An unintended natural experiment is in
progress to test whether the rate of advance slows down. At the current rate of
advance the species will reach the oceanic North Sea by 2018/2019, therefore time
for taking preventative action is short.
PMID- 28423030
TI - Molecular characterization of Cryptosporidium and Giardia from the Tasmanian
devil (Sarcophilus harrisii).
AB - The Tasmanian devil (Sarcophilus harrisii) is a carnivorous marsupial found only
in the wild in Tasmania, Australia. Tasmanian devils are classified as endangered
and are currently threatened by devil facial tumour disease, a lethal
transmissible cancer that has decimated the wild population in Tasmania. To
prevent extinction of Tasmanian devils, conservation management was implemented
in 2003 under the Save the Tasmanian Devil Program. This study aimed to assess if
conservation management was altering the interactions between Tasmanian devils
and their parasites. Molecular tools were used to investigate the prevalence and
diversity of two protozoan parasites, Cryptosporidium and Giardia, in Tasmanian
devils. A comparison of parasite prevalence between wild and captive Tasmanian
devils showed that both Cryptosporidium and Giardia were significantly more
prevalent in wild devils (p < 0.05); Cryptosporidium was identified in 37.9% of
wild devils but only 10.7% of captive devils, while Giardia was identified in
24.1% of wild devils but only 0.82% of captive devils. Molecular analysis
identified the presence of novel genotypes of both Cryptosporidium and Giardia.
The novel Cryptosporidium genotype was 98.1% similar at the 18S rDNA to
Cryptosporidium varanii (syn. C. saurophilum) with additional samples identified
as C. fayeri, C. muris, and C. galli. Two novel Giardia genotypes, TD genotype 1
and TD genotype 2, were similar to G. duodenalis from dogs (94.4%) and a Giardia
assemblage A isolate from humans (86.9%). Giardia duodenalis BIV, a zoonotic
genotype of Giardia, was also identified in a single captive Tasmanian devil.
These findings suggest that conservation management may be altering host-parasite
interactions in the Tasmanian devil, and the presence of G. duodenalis BIV in a
captive devil points to possible human-devil parasite transmission.
PMID- 28423031
TI - Comorbidities of rheumatoid arthritis: Results from the Korean National Health
and Nutrition Examination Survey.
AB - This study aimed to evaluate the prevalence of comorbidities in patients with
rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012
Korea National Health and Nutrition Examination Survey (KNHANES), which assesses
the general health status of populations in South Korea using interviews and
basic health assessment, was analyzed retrospectively. Weighted prevalence and
odds ratio (OR) of comorbidities were analyzed in patients with RA compared with
the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was
1.5%. Patients with RA were older and more female predominant than subjects
without RA. The prevalence of living in an urban area, college graduation,
alcohol consumption and smoking was lower in patients with RA than non-RA.
Patients with RA had more comorbidities including hypertension, dyslipidemia,
myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon
cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and
chronic kidney disease. After adjusting socioeconomic and lifestyle
characteristics, RA was associated with an increased prevalence of MI or angina
(OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09,
p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR
1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and
hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA
population. Prevalence of solid cancer was not significantly associated with RA
after adjustment.
PMID- 28423032
TI - Complete study demonstrating the absence of rhabdovirus in a distinct Sf9 cell
line.
AB - A putative novel rhabdovirus (SfRV) was previously identified in a Spodoptera
frugiperda cell line (Sf9 cells [ATCC CRL-1711 lot 58078522]) by next generation
sequencing and extensive bioinformatic analysis. We performed an extensive
analysis of our Sf9 cell bank (ATCC CRL-1711 lot 5814 [Sf9L5814]) to determine
whether this virus was already present in cells obtained from ATCC in 1987.
Inverse PCR of DNA isolated from Sf9 L5814 cellular DNA revealed integration of
SfRV sequences in the cellular genome. RT-PCR of total RNA showed a deletion of
320 nucleotides in the SfRV RNA that includes the transcriptional motifs for
genes X and L. Concentrated cell culture supernatant was analyzed by sucrose
density gradient centrifugation and revealed a single band at a density of 1.14
g/ml. This fraction was further analysed by electron microscopy and showed
amorphous and particulate debris that did not resemble a rhabdovirus in
morphology or size. SDS-PAGE analysis confirmed that the protein composition did
not contain the typical five rhabdovirus structural proteins and LC-MS/MS
analysis revealed primarily of exosomal marker proteins, the SfRV N protein, and
truncated forms of SfRV N, P, and G proteins. The SfRV L gene fragment RNA
sequence was recovered from the supernatant after ultracentrifugation of the 1.14
g/ml fraction treated with diethyl ether suggesting that the SfRV L gene fragment
sequence is not associated with a diethyl ether resistant nucleocapsid.
Interestingly, the 1.14 g/ml fraction was able to transfer baculovirus DNA into
Sf9L5814 cells, consistent with the presence of functional exosomes. Our results
demonstrate the absence of viral particles in ATCC CRL-1711 lot 5814 Sf9 cells in
contrast to a previous study that suggested the presence of infectious
rhabdoviral particles in Sf9 cells from a different lot. This study highlights
how cell lines with different lineages may present different virosomes and
therefore no general conclusions can be drawn across Sf9 cells from different
laboratories.
PMID- 28423033
TI - Can soda ash dumping grounds provide replacement habitats for digger wasps
(Hymenoptera, Apoidea, Spheciformes)?
AB - BACKGROUND: Published sources document a loss of biodiversity at an extreme rate,
mainly because natural and semi-natural ecosystems are becoming fragmented and
isolated, thus losing their biological functions. These changes significantly
influence biological diversity, which is a complex phenomenon that changes over
time. Contemporary ecologists must therefore draw attention to anthropogenic
replacement habitats and increase their conservation status. In our studies we
show the positive role of soda ash dumping grounds as an alternative habitat for
digger wasps, especially the thermophilic species. METHODOLOGY/PRINCIPAL
FINDINGS: In the years 2007-2010 we carried out investigations in postindustrial
soda ash dumping grounds located in Central Poland. We demonstrated that these
areas serve as replacement habitats for thermophilic species of Spheciformes and,
indirectly, for their potential prey. The studies were conducted in three
microhabitat types, varying in soil moisture, salinity and alkalinity, that were
changing in the course of ecological succession. We trapped 2571 specimens
belonging to 64 species of digger wasps. Species typical of open sunny spaces
comprised 73% of the whole inventory. The obtained results suggest that the stage
of succession determines the richness, abundance and diversity of Spheciformes.
The most favorable conditions for digger wasps were observed in habitats at late
successional stages. CONCLUSIONS/SIGNIFICANCE: Our results clearly showed that
these habitats were replacement habitats for thermophilous Spheciformes,
including rare taxa that require genetic, species and ecosystem protection,
according to the Biodiversity Convention. We showed that some types of industry
might play a positive role in the preservation of taxa in the landscape, and that
even degraded industrial wasteland can replace habitats under anthropopressure,
serving as refugia of biological diversity, especially for disturbance-dependent
species.
PMID- 28423034
TI - Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within
tumour from perineural squamous cell carcinoma patients.
AB - Perineural spread of tumour cells along cranial nerves is a severe complication
of primary cutaneous squamous cell carcinomas of the head and neck region. While
surgical excision of the tumour is the treatment of choice, removal of all the
tumour is often complicated by the neural location and recurrence is frequent.
Non-invasive immune treatments such as checkpoint inhibitor blockade may be
useful in this set of tumours although little is understood about the immune
response to perineural spread of squamous cell carcinomas. Immunohistochemistry
studies suggest that perineural tumour contains a lymphocyte infiltrate but it is
difficult to quantitate the different proportions of immune cell subsets and
expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow
cytometry of excised perineural tumour tissue, we show that a T cell infiltrate
is prominent in addition to less frequent B cell, NK cell and NKT cell
infiltrates. CD8 T cells are more frequent than other T cells in the tumour
tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing
cells was significantly greater in the tumour relative to the blood, a pattern
that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using
immunohistochemistry, PD-1 and PD-L1-expression could be detected in close
proximity amongst perineural tumour tissue. The data suggest that perineural SCC
contains a mixture of immune cells with a predominant T cell infiltrate
containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+
and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local
antibody blockade of these checkpoint inhibitors.
PMID- 28423035
TI - Genetic profiling of putative breast cancer stem cells from malignant pleural
effusions.
AB - A common symptom during late stage breast cancer disease is pleural effusion,
which is related to poor prognosis. Malignant cells can be detected in pleural
effusions indicating metastatic spread from the primary tumor site. Pleural
effusions have been shown to be a useful source for studying metastasis and for
isolating cells with putative cancer stem cell (CSC) properties. For the present
study, pleural effusion aspirates from 17 metastatic breast cancer patients were
processed to propagate CSCs in vitro. Patient-derived aspirates were cultured
under sphere forming conditions and isolated primary cultures were further sorted
for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally,
sphere forming efficiency of CSC and non-CSC subpopulations was determined. In
order to genetically characterize the different tumor subpopulations, DNA was
isolated from pleural effusions before and after cell sorting, and compared with
corresponding DNA copy number profiles from primary tumors or bone metastasis
using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells
had a higher potential to form spheres when compared to CSC subpopulations. In
most cases, cell sorting did not yield sufficient cells for copy number analysis.
A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant
copy number profiles similar to the respective primary tumor. However, most
sorted subpopulations showed a balanced profile indicating an insufficient amount
of tumor cells and low sensitivity of the sequencing method. Finally, we were
able to establish a long term cell culture from one pleural effusion sample,
which was characterized in detail. In conclusion, we confirm that pleural
effusions are a suitable source for enrichment of putative CSC. However,
sequencing based molecular characterization is impeded due to insufficient
sensitivity along with a high number of normal contaminating cells, which are
masking genetic alterations of rare cancer (stem) cells.
PMID- 28423036
TI - Metabolic syndrome, serum uric acid and renal risk in patients with T2D.
AB - BACKGROUND AND AIMS: Metabolic Syndrome (Mets) and increased serum uric acid
(SUA), are well known renal risk predictors and often coexist in patients with
type 2 diabetes (T2D). Whether they independently contribute to the onset of CKD
is at present unclear. METHODS AND RESULTS: Within the AMD Annals database we
identified patients with T2D and normal renal function and urine albumin
excretion at baseline and regular follow-up visits during a 4-year period. Blood
pressure, BMI, HDL, triglycerides, and SUA were available in 14,267 patients. The
association between Mets and/or hyperuricemia (HU, top fifth gender specific
quintile) and the occurrence of renal outcomes were evaluated. RESULTS: At
baseline 59% of patients (n = 8,408) showed Mets and 18% (n = 2,584) HU. Over the
4-year follow-up, 14% (n = 1,990) developed low eGFR (i.e. below 60 mL/min/1.73
m2), and 26% (n = 3,740) albuminuria. After adjustment for confounders,
BP>=130/85, low HDL, triglycerides >=150 and HU were independently related to the
development of low eGFR (1.57, P<0.001; 1.13, P = 0.056; 1.18, P = 0.008; 1.26, P
= 0.001) and of albuminuria (1.35, P<0.001; 1.18, P = 0.001; 1.15, P = 0.002;
1.24, P = 0.001), respectively. The incidence of low eGFR was higher in patients
with HU independent of the presence or absence of Mets (21%, OR 1.30, p = 0.009
and 20%, 1.57, p<0.000 respectively), while albuminuria occurred more frequently
in those with Mets and HU (32%, OR 1.25, p = 0.005) as compared to the reference
group. CONCLUSIONS: HU and Mets are independent predictors of CKD and its
individual components in patients with T2D.
PMID- 28423037
TI - Identification of candidate chemosensory genes by transcriptome analysis in
Loxostege sticticalis Linnaeus.
AB - Loxostege sticticalis Linnaeus is an economically important agricultural pest,
and the larvae cause great damage to crops, especially in Northern China.
However, effective and environmentally friendly chemical methods for controlling
this pest have not been discovered to date. In the present study, we performed
HiSeq2500 sequencing of transcriptomes of the male and female adult antennae,
adult legs and third instar larvae, and we identified 54 candidate odorant
receptors (ORs), including 1 odorant receptor coreceptor (Orco) and 5 pheromone
receptors (PRs), 18 ionotropic receptors (IRs), 13 gustatory receptors (GRs), 34
odorant binding proteins (OBPs), including 1 general odorant binding protein
(GOBP1) and 3 pheromone binding proteins (PBPs), 10 chemosensory proteins (CSPs)
and 2 sensory neuron membrane proteins (SNMPs). The results of RNA-Seq and RT
qPCR analyses showed the expression levels of most genes in the antennae were
higher than that in the legs and larvae. Furthermore, PR4, OR1-4, 7-11, 13-15,
23, 29-32, 34, 41, 43, 47/IR7d.2/GR5b, 45, 7/PBP2-3, GOBP1, OBP3, 8 showed female
antennae-biased expression, while PR1/OBP2, 7/IR75d/CSP2 showed male antennae
biased expression. However, IR1, 7d.3, 68a/OBP11, 20-22, 28/CSP9 had larvae
enriched expression, and OBP15, 17, 25, 29/CSP5 were mainly expressed in the
legs. The results shown above indicated that these genes might play a key role in
foraging, seeking mates and host recognition in the L. sticticalis. Our findings
will provide the basic knowledge for further studies on the molecular mechanisms
of the olfactory system of L. sticticalis and potential novel targets for pest
control strategies.
PMID- 28423038
TI - Attentional bias modification training for insomnia: A double-blind placebo
controlled randomized trial.
AB - BACKGROUND: Attentional bias toward sleep-related information is believed to play
a key role in insomnia. If attentional bias is indeed of importance, changing
this bias should then in turn have effects on insomnia complaints. In this double
blind placebo controlled randomized trial we investigated the efficacy of
attentional bias modification training in the treatment of insomnia. METHOD: We
administered baseline, post-test, and one-week follow-up measurements of insomnia
severity, sleep-related worry, depression, and anxiety. Participants meeting DSM
5 criteria for insomnia were randomized into an attentional bias training group
(n = 67) or a placebo training group (n = 70). Both groups received eight
training sessions over the course of two weeks. All participants kept a sleep
diary for four consecutive weeks (one week before until one week after the
training sessions). RESULTS: There was no additional benefit for the attentional
bias training over the placebo training on sleep-related indices/outcome
measures. CONCLUSIONS: The absence of the effect may be explained by the fact
that there was neither attentional bias at baseline nor any reduction in the bias
after the training. Either way, this study gives no support for attentional bias
modification training as a stand-alone intervention for ameliorating insomnia
complaints.
PMID- 28423039
TI - Electricity forecasting on the individual household level enhanced based on
activity patterns.
AB - Leveraging smart metering solutions to support energy efficiency on the
individual household level poses novel research challenges in monitoring usage
and providing accurate load forecasting. Forecasting electricity usage is an
especially important component that can provide intelligence to smart meters. In
this paper, we propose an enhanced approach for load forecasting at the household
level. The impacts of residents' daily activities and appliance usages on the
power consumption of the entire household are incorporated to improve the
accuracy of the forecasting model. The contributions of this paper are threefold:
(1) we addressed short-term electricity load forecasting for 24 hours ahead, not
on the aggregate but on the individual household level, which fits into the
Residential Power Load Forecasting (RPLF) methods; (2) for the forecasting, we
utilized a household specific dataset of behaviors that influence power
consumption, which was derived using segmentation and sequence mining algorithms;
and (3) an extensive load forecasting study using different forecasting
algorithms enhanced by the household activity patterns was undertaken.
PMID- 28423040
TI - Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type
10 (SCA10) expansions.
AB - Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia
disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the
ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion
contains a complex sequence of penta- and heptanucleotide interruption motifs
which is followed by a pure tract of tandem ATCCT repeats of unknown length at
its 3'-end. Intriguingly, expansions that carry these interruption motifs
correlate with an epileptic seizure phenotype and are unstable despite the theory
that interruptions are expected to stabilize expanded repeats. To examine the
apparent contradiction of unstable, interruption-positive SCA10 expansion alleles
and to determine whether the instability originates outside of the interrupted
region, we sequenced approximately 1 kb of the 5'-end of SCA10 expansions using
the ATCCT-PCR product in individuals across multiple generations from four SCA10
families. We found that the greatest instability within this region occurred in
paternal transmissions of the allele in stretches of pure ATTCT motifs while the
intervening interrupted sequences were stable. Overall, the ATCCT interruption
changes by only one to three repeat units and therefore cannot account for the
instability across the length of the disease allele. We conclude that the AT-rich
interruptions locally stabilize the SCA10 expansion at the 5'-end but do not
completely abolish instability across the entire span of the expansion. In
addition, analysis of the interruption alleles across these families support a
parsimonious single origin of the mutation with a shared distant ancestor.
PMID- 28423041
TI - Modeling the shape and composition of the human body using dual energy X-ray
absorptiometry images.
AB - There is growing evidence that body shape and regional body composition are
strong indicators of metabolic health. The purpose of this study was to develop
statistical models that accurately describe holistic body shape, thickness, and
leanness. We hypothesized that there are unique body shape features that are
predictive of mortality beyond standard clinical measures. We developed
algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans
into body thickness and leanness images. We performed statistical appearance
modeling (SAM) and principal component analysis (PCA) to efficiently encode the
variance of body shape, leanness, and thickness across sample of 400 older
Americans from the Health ABC study. The sample included 200 cases and 200
controls based on 6-year mortality status, matched on sex, race and BMI. The
final model contained 52 points outlining the torso, upper arms, thighs, and bony
landmarks. Correlation analyses were performed on the PCA parameters to identify
body shape features that vary across groups and with metabolic risk. Stepwise
logistic regression was performed to identify sex and race, and predict mortality
risk as a function of body shape parameters. These parameters are novel body
composition features that uniquely identify body phenotypes of different groups
and predict mortality risk. Three parameters from a SAM of body leanness and
thickness accurately identified sex (training AUC = 0.99) and six accurately
identified race (training AUC = 0.91) in the sample dataset. Three parameters
from a SAM of only body thickness predicted mortality (training AUC = 0.66,
validation AUC = 0.62). Further study is warranted to identify specific
shape/composition features that predict other health outcomes.
PMID- 28423042
TI - Transforming growth factor beta1 enhances heme oxygenase 1 expression in human
synovial fibroblasts by inhibiting microRNA 519b synthesis.
AB - BACKGROUND: Osteoarthritis (OA) is manifested by synovial inflammation and
cartilage destruction that is directly linked to synovitis, joint swelling and
pain. In the light of the role of synovium in the pathogenesis and the symptoms
of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms
and progression of OA. Transforming growth factor beta 1 (TGF-beta1), a secreted
homodimeric protein, possesses unique and potent anti-inflammatory and immune
regulatory properties in many cell types. Heme oxygenase 1 (HO-1) is an inducible
anti-inflammatory and stress responsive enzyme that has been proven to prevent
injuries caused by many diseases. Despite the similar anti-inflammatory profile
and their involvement in the pathogenesis of arthritic diseases, no studies have
as yet explored the possibility of any association between the expression of TGF
beta1 and HO-1. METHODOLOGY/PRINCIPAL FINDINGS: TGF-beta1-induced HO-1 expression
was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and
enzyme inhibitors were utilized to determine the intermediate involved in the
signal transduction pathway. We showed that TGF-beta1 stimulated the synthesis of
HO-1 in a concentration- and time-dependent manner, which can be mitigated by
blockade of the phospholipase (PLC)gamma/protein kinase C alpha (PKC)alpha
pathway. We also showed that the expression of miRNA-519b, which blocks HO-1
transcription, is inhibited by TGF-beta1, and the suppression of miRNA 519b could
be reversed via blockade of the PLCgamma/PKCalpha pathway.
CONCLUSIONS/SIGNIFICANCE: TGF-beta1 stimulated the expression of HO-1 via
activating the PLCgamma/PKCalpha pathway and suppressing the downstream
expression of miRNA-519b. These results may shed light on the pathogenesis and
treatment of OA.
PMID- 28423043
TI - Essential neonatal care utilization and associated factors among mothers in
public health facilities of Aksum Town, North Ethiopia, 2016.
AB - BACKGROUND: Globally, neonatal death accounts about 44% of child death in 2013.
Ethiopia is one of the ten countries with the highest number of neonatal death.
Worldwide, more than 43% of deaths among under five year children is contributed
by neonates. Half of the neonatal death occur in the first day of life.
Recommendations about newborn care practices may conflict with local beliefs and
practices. So, it is important to understand the existing newborn care practice
and factors affecting it in order to take interventions so as to decrease
neonatal death. OBJECTIVE: To assess magnitude of essential neonatal care
utilization and associated factors among women visiting public health facilities
in Aksum Town, Tigray, Northern Ethiopia, 2015. METHODS: Facility based cross
sectional study was conducted from December 30, 2015 to January 31, 2016.The
sampled population are 423 women who gave live births within the last 6 months
prior to data collection. Systematic random sampling technique was employed. Data
were entered, coded and cleaned using Epi info version 7, and SPSS Version 21
software was used for analysis. Both bivariable and multivariable logistic
regression models were used to determine factors associated with essential
neonatal care utilization. Variables with P-value <0.2 in the bivariable logistic
regression model were included in to multivariable logistic regression model, and
finally variables with P-value <0.05 were considered as independent factors. Odds
ratio was used to measure strength of association at 95% confidence level.
RESULT: A total of 423 mothers included in the study. Prevalence of safe cord
care, optimal breast feeding, thermal care and baby received Tetracycline eye
ointment and vaccine at birth were 42.8%, 63.1%, 32.6% and 44.7% among the
respondents respectively. Only 113(26.7%) of the participants fulfilled essential
new born care practice. Occupation, parity and counseling on essential new born
care during delivery were significantly associated with utilization of essential
new born care. Employed women (AOR = 7.08; 95% CI (2.21, 12.72), 2-3 number of
deliveries (AOR = 1.84; 95% CI (1.04, 3.26) and received counseling about
essential new born car during delivery (AOR = 3.36; 95% CI (1.86, 6.08) were more
likely to practice essential neonatal care practice than their counterparts.
CONCLUSION AND RECOMMENDATION: Around three-fourth of mothers were not practicing
Essential Newborn Care (ENC). Occupation, parity and essential new born care
counseling during delivery were significantly associated with utilization of ENC.
Promotion of information at community level, women empowerment and staff training
is recommended.
PMID- 28423044
TI - The long term outcome of micturition, defecation and sexual function after spinal
surgery for cauda equina syndrome.
AB - BACKGROUND: Cauda equina syndrome (CES) is a rare neurologic complication of
lumbar herniated disc for which emergency surgical decompression should be
undertaken. Despite the common belief that the restoration of functions that are
affected by CES can take several years postoperatively, follow up seldom exceeds
the first year after surgery. Long term outcome of especially micturition,
defecation and sexual function-which are by definition affected in CES-are
unknown. The aim of this study is to evaluate 1) postoperative long term outcome
of micturition, defecation and sexual function in CES patients 2) attitude of
patients towards received hospital care with regard to (recovery of) these
functions. METHODS: CES patients were selected by screening the records of all
patients operated on lumbar herniated disc in our university hospital between
1995-2010. A questionnaire was sent to the selected CES patients evaluating
current complaints of micturition, defecation and sexual function and attitude
towards delivered care with focus on micturition, defecation and sexual function.
RESULTS: Thirty-seven of 66 eligible CES patients were included (response rate
71%, inclusion rate 56%). Median time after surgery was 13.8 years (range 5.8
21.8 years). Dysfunction at follow up was highly prevalent: 38% micturition
dysfunction, 43% defecation dysfunction and 54% sexual dysfunction. Younger age
at presentation was associated with sexual dysfunction at follow up: for every
year younger at presentation, odds ratio for sexual dysfunction at follow up was
1.11 (p = 0.035). Other associations with outcome were not identified. Two-third
of the CES patients wished their neurosurgeon had given them more prognostic
information about micturition, defecation and sexual function. CONCLUSION: The
presented data demonstrate that dysfunction of micturition, defecation and sexual
function are still highly prevalent in a large number of CES patients even years
postoperatively. These alarming follow up data probably have a devastating effect
on personal perceived quality of life, which should be studied in more detail.
CES patients communicate a clear demand for more prognostic information. The
presented figures enable clinicians to inform their CES patients more
realistically about long term postoperative outcome of micturition, defecation
and sexual function after surgical intervention.
PMID- 28423046
TI - Genetic structure and isolation by altitude in rice landraces of Yunnan, China
revealed by nucleotide and microsatellite marker polymorphisms.
AB - Rice landraces, a genetic reservoir for varietal improvement, are developed by
farmers through artificial selection during the long-term domestication process.
To efficiently conserve, manage, and use such germplasm resources, an
understanding of the genetic structure and differentiation of local rice
landraces is required. In this study, we analyzed 188 accessions of rice
landraces collected from localities across an altitudinal gradient from 425 to 2,
274 m above sea level in Yunnan Province, China using ten target genes and 48 SSR
markers. We detected clear differentiation of the rice landraces into indica and
japonica groups and further separation of the accessions in each group into two
subgroups according to altitude, including a lower altitude subgroup and higher
altitude subgroup. The AMOVA results showed significant genetic differentiation
among altitude zones at SSRs and most genes, except Os1977 and STS22. We further
determined that differentiation among landrace populations followed a model of
isolation by altitude, in which gene flow was higher among populations at similar
altitude levels than across different altitude levels. Our findings demonstrated
that both adaptation to altitude and altitude-dependent gene flow played key
roles in the genetic differentiation of rice landraces in Yunnan, China.
PMID- 28423045
TI - Characterization of antennal sensilla, larvae morphology and olfactory genes of
Melipona scutellaris stingless bee.
AB - There is growing evidence in the literature suggesting that caste differentiation
in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona,
is triggered by environmental signals, particularly a primer pheromone. With the
proper amount of food and a chemical stimulus, 25% of females emerge as queens,
in agreement with a long-standing "two loci/two alleles model" proposed in the
1950s. We surmised that these larvae must be equipped with an olfactory system
for reception of these chemical signals. Here we describe for the first time the
diversity of antennal sensilla in adults and the morphology of larvae of M.
scutellaris. Having found evidence for putative olfactory sensilla in larvae, we
next asked whether olfactory proteins were expressed in larvae. Since the
molecular basis of M. scutellaris is still unknown, we cloned olfactory genes
encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M.
scutellaris cDNA template and primers designed on the basis CSPs and OBPs
previously reported from the European honeybee, Apis mellifera. We cloned two CSP
and two OBP genes and then attempted to express the proteins encoded by these
genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain
variable fragment antibody library, we generated anti-MscuOBP8 monoclonal
antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds
specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed
in M. scutellaris larvae and it is located in the mandibular region, thus further
supporting the hypothesis of olfactory function in immature stages. Lastly,
molecular modeling suggests that MscuOBP8 may function as a carrier of primer
pheromones or other ligands.
PMID- 28423047
TI - Impact of body condition on influenza A virus infection dynamics in mallards
following a secondary exposure.
AB - Migratory waterfowl are often viewed as vehicles for the global spread of
influenza A viruses (IAVs), with mallards (Anas platyrhynchos) implicated as
particularly important reservoir hosts. The physical demands and energetic costs
of migration have been shown to influence birds' body condition; poorer body
condition may suppress immune function and affect the course of IAV infection.
Our study evaluated the impact of body condition on immune function and viral
shedding dynamics in mallards naturally exposed to an H9 IAV, and then
secondarily exposed to an H4N6 IAV. Mallards were divided into three treatment
groups of 10 birds per group, with each bird's body condition manipulated as a
function of body weight by restricting food availability to achieve either a
10%, -20%, or control body weight class. We found that mallards exhibit moderate
heterosubtypic immunity against an H4N6 IAV infection after an infection from an
H9 IAV, and that body condition did not have an impact on shedding dynamics in
response to a secondary exposure. Furthermore, body condition did not affect
aspects of the innate and adaptive immune system, including the acute phase
protein haptoglobin, heterophil/lymphocyte ratios, and antibody production.
Contrary to recently proposed hypotheses and some experimental evidence, our data
do not support relationships between body condition, infection and
immunocompetence following a second exposure to IAV in mallards. Consequently,
while annual migration may be a driver in the maintenance and spread of IAVs, the
energetic demands of migration may not affect susceptibility in mallards.
PMID- 28423048
TI - Correction: Impact of self-reported symptoms of allergic rhinitis and asthma on
sleep disordered breathing and sleep disturbances in the elderly with
polysomnography study.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173075.].
PMID- 28423049
TI - InMAP: A model for air pollution interventions.
AB - Mechanistic air pollution modeling is essential in air quality management, yet
the extensive expertise and computational resources required to run most models
prevent their use in many situations where their results would be useful. Here,
we present InMAP (Intervention Model for Air Pollution), which offers an
alternative to comprehensive air quality models for estimating the air pollution
health impacts of emission reductions and other potential interventions. InMAP
estimates annual-average changes in primary and secondary fine particle (PM2.5)
concentrations-the air pollution outcome generally causing the largest monetized
health damages-attributable to annual changes in precursor emissions. InMAP
leverages pre-processed physical and chemical information from the output of a
state-of-the-science chemical transport model and a variable spatial resolution
computational grid to perform simulations that are several orders of magnitude
less computationally intensive than comprehensive model simulations. In
comparisons run here, InMAP recreates comprehensive model predictions of changes
in total PM2.5 concentrations with population-weighted mean fractional bias (MFB)
of -17% and population-weighted R2 = 0.90. Although InMAP is not specifically
designed to reproduce total observed concentrations, it is able to do so within
published air quality model performance criteria for total PM2.5. Potential uses
of InMAP include studying exposure, health, and environmental justice impacts of
potential shifts in emissions for annual-average PM2.5. InMAP can be trained to
run for any spatial and temporal domain given the availability of appropriate
simulation output from a comprehensive model. The InMAP model source code and
input data are freely available online under an open-source license.
PMID- 28423050
TI - Correction: Stiffness Effects in Rocker-Soled Shoes: Biomechanical Implications.
AB - [This corrects the article DOI: 10.1371/journal.pone.0169151.].
PMID- 28423051
TI - Biochemical and molecular characterization of the isocitrate dehydrogenase with
dual coenzyme specificity from the obligate methylotroph Methylobacillus
Flagellatus.
AB - The isocitrate dehydrogenase (MfIDH) with unique double coenzyme specificity from
Methylobacillus flagellatus was purified and characterized, and its gene was
cloned and overexpressed in E. coli as a fused protein. This enzyme is
homodimeric,-with a subunit molecular mass of 45 kDa and a specific activity of
182 U mg -1 with NAD+ and 63 U mg -1 with NADP+. The MfIDH activity was dependent
on divalent cations and Mn2+ enhanced the activity the most effectively. MfIDH
exhibited a cofactor-dependent pH-activity profile. The optimum pH values were
8.5 (NAD+) and 6.0 (NADP+).The Km values for NAD+ and NADP+ were 113 MUM and 184
MUM respectively, while the Km values for DL-isocitrate were 9.0 MUM (NAD+), 8.0
MUM (NADP+). The MfIDH specificity (kcat/Km) was only 5-times higher for NAD+
than for NADP+. The purified MfIDH displayed maximal activity at 60 degrees C.
Heat-inactivation studies showed that the MfIDH was remarkably thermostable,
retaining full activity at 50 degrees C and losting ca. 50% of its activity after
one hour of incubation at 75 degrees C. The enzyme was insensitive to the
presence of intermediate metabolites, with the exception of 2 mM ATP, which
caused 50% inhibition of NADP+-linked activity. The indispensability of the N6
amino group of NAD(P)+ in its binding to MfIDH was demonstrated. MfIDH showed
high sequence similarity with bacterial NAD(P)+-dependent type I isocitrate
dehydrogenases (IDHs) rather than with eukaryotic NAD+-dependent IDHs. The unique
double coenzyme specificity of MfIDH potentially resulted from the Lys340, Ile341
and Ala347 residues in the coenzyme-binding site of the enzyme. The discovery of
a type I IDH with double coenzyme specificity elucidates the evolution of this
subfamily IDHs and may provide fundamental information for engineering enzymes
with desired properties.
PMID- 28423052
TI - Inflammation-induced fetal growth restriction in rats is associated with
increased placental HIF-1alpha accumulation.
AB - INTRODUCTION: Hypoxia-inducible factor 1-alpha (HIF-1alpha) is the oxygen
sensitive subunit of the transcription factor HIF-1, and its expression is
increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal
growth restriction (FGR) and PE often share a common pathophysiology; however, it
is unknown whether increased placental HIF-1alpha occurs in FGR. We previously
demonstrated that aberrant maternal inflammation in rats resulted in altered
utero-placental perfusion and FGR, both of which were prevented by administration
of the nitric oxide mimetic glyceryl trinitrate (GTN). Our aim here was to
determine whether abnormal maternal inflammation causing FGR is linked to
placental HIF-1alpha accumulation and whether GTN administration could prevent
increases in placental HIF-1alpha. METHODS: Levels of inflammatory factors in
maternal plasma were measured using a multiplex assay after an injection of low
dose lipopolysaccharide (LPS) to rats on gestational day (GD) 13.5. Following
three additional daily LPS injections from GD14.5-16.5, GD17.5 placentas were
harvested for HIF-1alpha immunolocalisation; serial sections were also stained
for the hypoxia marker pimonidazole. A subset of rats received LPS injections
along with GTN delivered continuously (25 MUg/h via a transdermal patch) on
GD12.5-GD17.5. RESULTS: Within two hours of LPS administration, levels of
maternal pro-inflammatory cytokines were increased compared with saline-treated
controls. GD17.5 placentas of growth-restricted fetuses exhibited increased HIF
1alpha accumulation; however, this did not correlate with pimonidazole staining
for which no differences were observed between groups. Furthermore, the LPS
mediated increases in maternal inflammatory cytokine levels and placental HIF
1alpha accumulation did not occur in rats treated with GTN. DISCUSSION: Our
results demonstrate that inflammation-induced FGR is associated with increased
placental HIF-1alpha accumulation; however, expression of this transcription
factor may not correlate with regions of hypoxia in late-gestation placentas. The
GTN-mediated attenuation of placental HIF-1alpha accumulation in LPS-treated rats
provides insight into the mechanism by which GTN improves inflammation-induced
complications of pregnancy.
PMID- 28423053
TI - "She's a dog at the end of the day": Guide dog owners' perspectives on the
behaviour of their guide dog.
AB - A guide dog is a domestic dog (Canis familiaris) that is specifically educated to
provide mobility support to a blind or visually impaired owner. Current dog
suitability assessments focus on behavioural traits, including: trainability,
reactivity or attention to environmental stimuli, low aggressiveness, fearfulness
and stress behaviour, energy levels, and attachment behaviour. The aim of this
study was to find out which aspects of guide dog behaviour are of key importance
to guide dog owners themselves. Sixty-three semi-structured interview surveys
were carried out with guide dog owners. Topics included the behaviour of their
guide dog both within and outside their working role, and also focused on
examples of behaviour which might be considered outside a guide dog owner's
typical expectations. Both positive and negative examples and situations were
covered. This allowed for the discovery of new perspectives and emerging themes
on living and working with a guide dog. Thematic analysis of the results reveals
that a dog's safe behaviour in the face of traffic was the most important
positive aspect of a guide dog's behaviour and pulling or high tension on the
lead and /or harness was the most discussed negative aspect. Other aspects of
guide dog behaviour were highlighted as particularly pleasing or disappointing by
owners including attentiveness to the task, work, environment and owner;
confidence in work and decision making (with confident dogs resulting in
confident owners) obedience and control; calmness and locating objectives. The
results reveal important areas of behaviour that are not currently considered
priorities in guide dog assessments; these key areas were consistency of
behaviour, the dog's maturity and the dog's behaviour in relation to children.
The survey revealed a large range in what owners considered problematic or
pleasing behaviours and this highlights the heterogeneity in guide dog owners and
the potential multifarious roles of the guide dog. This study contributes to the
literature on which behaviour is considered appropriate or inappropriate in dogs
and on the nature of human-animal interactions.
PMID- 28423054
TI - Sleep duration and quality in relation to chronic kidney disease and glomerular
hyperfiltration in healthy men and women.
AB - BACKGROUND: It is unclear whether sleep duration and quality are associated with
chronic kidney disease (CKD) and glomerular hyperfiltration. The aim of this
study was to examine the association of sleep duration and quality with CKD and
glomerular hyperfiltration in young and middle-aged adults. METHODS: We conducted
a cross-sectional study of men and women who underwent a health checkup
examination, including assessment of sleep duration and quality (n = 241,607).
Chronic kidney disease (CKD) was defined as an estimated glomerular filtration
rate (eGFR) less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was
defined as eGFR above the age-/sex-specific 95th percentile. RESULTS: In a
multinomial logistic regression analysis adjusting for relevant confounders, the
adjusted prevalence ratios for CKD (95% confidence interval) comparing sleep
durations of <= 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55), 0.93
(0.75-1.14), 0.97 (0.75-1.26), and 1.56 (1.06-2.30) in men and 0.98 (0.68-1.43),
1.03 (0.72-1.46), 1.39 (0.97-2.00), and 1.31 (0.78-2.22) in women, respectively.
The corresponding prevalence ratios (95% confidence interval) for glomerular
hyperfiltration were 1.00 (0.93-1.08), 0.97 (0.91-1.03), 1.03 (0.94-1.13), and
1.39 (1.13-1.72) in men and 1.04 (0.95-1.14), 0.96 (0.90-1.04), 1.11 (1.02-1.20),
and 1.28 (1.14-1.45) in women, respectively. Poor subjective sleep quality was
associated with glomerular hyperfiltration in men and women. CONCLUSION: In this
large study of young and middle-aged adults, we found that long sleep duration
was associated with CKD and glomerular hyperfiltration. Additionally, poor
subjective sleep quality was associated with increased prevalence of glomerular
hyperfiltration, suggesting the importance of adequate quantity and quality of
sleep for kidney function.
PMID- 28423055
TI - Comparative analysis of the expression level of recombinant ginsenoside
transforming beta-glucosidase in GRAS hosts and mass production of the
ginsenoside Rh2-Mix.
AB - The ginsenoside Rh2, a pharmaceutically active component of ginseng, is known to
have anticancer and antitumor effects. However, white ginseng and red ginseng
have extremely low concentrations of Rh2 or Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2,
and Rh3]. To enhance the production of food-grade ginsenoside Rh2, an edible
enzymatic bioconversion technique was developed adopting GRAS host strains. A
beta-glucosidase (BglPm), which has ginsenoside conversion ability, was expressed
in three GRAS host strains (Corynebacterium glutamicum, Saccharomyces cerevisiae
and Lactococus lactis) by using a different vector system. Enzyme activity in
these three GRAS hosts were 75.4%, 11.5%, and 9.3%, respectively, compared to
that in the E. coli pGEX 4T-1 expression system. The highly expressed BglPm_C in
C. glutamicum can effectively transform the ginsenoside Rg3-Mix [20(S)-Rg3, 20(R)
Rg3, Rk1, Rg5] to Rh2-Mix [20(S)-Rh2, 20(R)-Rh2, Rk2, Rh3] using a scaled-up
biotransformation reaction, which was performed in a 10-L jar fermenter at pH
6.5/7.0 and 37 degrees C for 24 h. To our knowledge, this is the first report in
which 50 g of PPD-Mix (Rb1, Rb2, Rb3, Rc, and Rd) as a starting substrate was
converted to ginsenoside Rg3-Mix by acid heat treatment and then 24.5-g Rh2-Mix
was obtained by enzymatic transformation of Rg3-Mix through by BglPm_C.
Utilization of this enzymatic method adopting a GRAS host could be usefully
exploited in the preparation of ginsenoside Rh2-Mix in cosmetics, functional
food, and pharmaceutical industries, thereby replacing the E. coli expression
system.
PMID- 28423056
TI - Hair and stress: A pilot study of hair and cytokine balance alteration in healthy
young women under major exam stress.
AB - Mouse models show that experimental stress mimicking prolonged life-stress
exposure enhances neurogenic inflammation, induces adaptive immunity cytokine
imbalance characterized by a shift to Type 1 T-helper cell cytokines and
increases apoptosis of epithelial cells. This affects hair growth in otherwise
healthy animals. In this study, we investigate whether a prolonged naturalistic
life-stress exposure affects cytokine balance and hair parameters in healthy
humans. 33 (18 exam, 15 comparison) female medical students with comparable
sociobiological status were analyzed during a stressful final examination period,
at three points in time (T) 12 weeks apart. T1 was before start of the learning
period, T2 between the three-day written exam and an oral examination, and T3
after a 12 week rest and recovery from the stress of the examination period.
Assessments included: self-reported distress and coping strategies (Perceived
Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress
[TICS]), COPE), cytokines in supernatants of stimulated peripheral blood
mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis).
Comparison between students participating in the final medical exam at T2 and non
exam students, revealed significantly higher stress perception in exam students.
Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and
hair parameters changed significantly from T1 to T2 in the exam group, but not
the control. However, no group differences were found for cytokine balance or
hair parameters at T2. The study concludes that in humans, naturalistic stress,
as perceived during participation in a major medical exam, has the potential to
shift the immune response to TH1 and transiently hamper hair growth, but these
changes stay within a physiological range. Findings are instructive for patients
suffering from hair loss in times of high stress. Replication in larger and more
diverse sample populations is required, to assess suitability of trichogram
analysis as biological outcome for stress studies.
PMID- 28423058
TI - Accurate phenotyping: Reconciling approaches through Bayesian model averaging.
AB - Genetic research into complex diseases is frequently hindered by a lack of clear
biomarkers for phenotype ascertainment. Phenotypes for such diseases are often
identified on the basis of clinically defined criteria; however such criteria may
not be suitable for understanding the genetic composition of the diseases.
Various statistical approaches have been proposed for phenotype definition;
however our previous studies have shown that differences in phenotypes estimated
using different approaches have substantial impact on subsequent analyses.
Instead of obtaining results based upon a single model, we propose a new method,
using Bayesian model averaging to overcome problems associated with phenotype
definition. Although Bayesian model averaging has been used in other fields of
research, this is the first study that uses Bayesian model averaging to reconcile
phenotypes obtained using multiple models. We illustrate the new method by
applying it to simulated genetic and phenotypic data for Kofendred personality
disorder-an imaginary disease with several sub-types. Two separate statistical
methods were used to identify clusters of individuals with distinct phenotypes:
latent class analysis and grade of membership. Bayesian model averaging was then
used to combine the two clusterings for the purpose of subsequent linkage
analyses. We found that causative genetic loci for the disease produced higher
LOD scores using model averaging than under either individual model separately.
We attribute this improvement to consolidation of the cores of phenotype clusters
identified using each individual method.
PMID- 28423057
TI - Insertion of a ligand to HER2 in gB retargets HSV tropism and obviates the need
for activation of the other entry glycoproteins.
AB - Herpes simplex virus (HSV) entry into the cells requires glycoproteins gD, gH/gL
and gB, activated in a cascade fashion by conformational modifications induced by
cognate receptors and intermolecular signaling. The receptors are nectin1 and
HVEM (Herpes virus entry mediator) for gD, and alphavbeta6 or alphavbeta8
integrin for gH. In earlier work, insertion of a single chain antibody (scFv) to
the cancer receptor HER2 (human epidermal growth factor receptor 2) in gD, or in
gH, resulted in HSVs specifically retargeted to the HER2-positive cancer cells,
hence in highly specific non-attenuated oncolytic agents. Here, the scFv to HER2
was inserted in gB (gBHER2). The insertion re-targeted the virus tropism to the
HER2-positive cancer cells. This was unexpected since gB is known to be a
fusogenic glycoprotein, not a tropism determinant. The gB-retargeted recombinant
offered the possibility to investigate how HER2 mediated entry. In contrast to wt
gB, the activation of the chimeric gBHER2 did not require the activation of the
gD and of gH/gL by their respective receptors. Furthermore, a soluble form of
HER2 could replace the membrane-bound HER2 in mediating virus entry, hinting that
HER2 acted by inducing conformational changes to the chimeric gB. This study
shows that (i) gB can be modified and become the major determinant of HSV
tropism; (ii) the chimeric gBHER2 bypasses the requirement for receptor-mediated
activation of other essential entry glycoproteins.
PMID- 28423059
TI - High resolution microscopy reveals significant impacts of ocean acidification and
warming on larval shell development in Laternula elliptica.
AB - Environmental stressors impact marine larval growth rates, quality and sizes.
Larvae of the Antarctic bivalve, Laternula elliptica, were raised to the D-larvae
stage under temperature and pH conditions representing ambient and end of century
projections (-1.6 degrees C to +0.4 degrees C and pH 7.98 to 7.65). Previous
observations using light microscopy suggested pH had no influence on larval
abnormalities in this species. Detailed analysis of the shell using SEM showed
that reduced pH is in fact a major stressor during development for this species,
producing D-larvae with abnormal shapes, deformed shell edges and irregular
hinges, cracked shell surfaces and even uncalcified larvae. Additionally, reduced
pH increased pitting and cracking on shell surfaces. Thus, apparently normal
larvae may be compromised at the ultrastructural level and these larvae would be
in poor condition at settlement, reducing juvenile recruitment and overall
survival. Elevated temperatures increased prodissoconch II sizes. However, the
overall impacts on larval shell quality and integrity with concurrent ocean
acidification would likely overshadow any beneficial results from warmer
temperatures, limiting populations of this prevalent Antarctic species.
PMID- 28423060
TI - Phosphatidylcholine-specific phospholipase C inhibition down- regulates CXCR4
expression and interferes with proliferation, invasion and glycolysis in glioma
cells.
AB - BACKGROUND: The chemokine receptor CXCR4 plays a crucial role in tumors,
including glioblastoma multiforme (GBM), the most aggressive glioma.
Phosphatidylcholine-specific phospholipase C (PC-PLC), a catabolic enzyme of PC
metabolism, is involved in several aspects of cancer biology and its inhibition
down-modulates the expression of growth factor membrane receptors interfering
with their signaling pathways. In the present work we investigated the possible
interplay between CXCR4 and PC-PLC in GBM cells. METHODS: Confocal microscopy,
immunoprecipitation, western blot analyses, and the evaluation of migration and
invasion potential were performed on U87MG cells after PC-PLC inhibition with the
xanthate D609. The intracellular metabolome was investigated by magnetic
resonance spectroscopy; lactate levels and lactate dehydrogenase (LDH) activity
were analyzed by colorimetric assay. RESULTS: Our studies demonstrated that CXCR4
and PC-PLC co-localize and are associated on U87MG cell membrane. D609 reduced
CXCR4 expression, cell proliferation and invasion, interfering with AKT and EGFR
activation and expression. Metabolic analyses showed a decrease in intracellular
lactate concentration together with a decrement in LDH activity. CONCLUSIONS: Our
data suggest that inhibition of PC-PLC could represent a new molecular approach
in glioma biology not only for its ability in modulating cell metabolism, glioma
growth and motility, but also for its inhibitory effect on crucial molecules
involved in cancer progression.
PMID- 28423061
TI - Muscle contributions to medial tibiofemoral compartment contact loading following
ACL reconstruction using semitendinosus and gracilis tendon grafts.
AB - BACKGROUND: The muscle-tendon properties of the semitendinosus (ST) and gracilis
(GR) are substantially altered following tendon harvest for the purpose of
anterior cruciate ligament reconstruction (ACLR). This study adopted a
musculoskeletal modelling approach to determine how the changes to the ST and GR
muscle-tendon properties alter their contribution to medial compartment contact
loading within the tibiofemoral joint in post ACLR patients, and the extent to
which other muscles compensate under the same external loading conditions during
walking, running and sidestep cutting. MATERIALS AND METHODS: Motion capture and
electromyography (EMG) data from 16 lower extremity muscles were acquired during
walking, running and cutting in 25 participants that had undergone an ACLR using
a quadruple (ST+GR) hamstring auto-graft. An EMG-driven musculoskeletal model was
used to estimate the medial compartment contact loads during the stance phase of
each gait task. An adjusted model was then created by altering muscle-tendon
properties for the ST and GR to reflect their reported changes following ACLR.
Parameters for the other muscles in the model were calibrated to match the
experimental joint moments. RESULTS: The medial compartment contact loads for the
standard and adjusted models were similar. The combined contributions of ST and
GR to medial compartment contact load in the adjusted model were reduced by 26%,
17% and 17% during walking, running and cutting, respectively. These deficits
were balanced by increases in the contribution made by the semimembranosus muscle
of 33% and 22% during running and cutting, respectively. CONCLUSION: Alterations
to the ST and GR muscle-tendon properties in ACLR patients resulted in reduced
contribution to medial compartment contact loads during gait tasks, for which the
semimembranosus muscle can compensate.
PMID- 28423062
TI - Filamentous fungal carbon catabolite repression supports metabolic plasticity and
stress responses essential for disease progression.
AB - Aspergillus fumigatus is responsible for a disproportionate number of invasive
mycosis cases relative to other common filamentous fungi. While many fungal
factors critical for infection establishment are known, genes essential for
disease persistence and progression are ill defined. We propose that fungal
factors that promote navigation of the rapidly changing nutrient and structural
landscape characteristic of disease progression represent untapped clinically
relevant therapeutic targets. To this end, we find that A. fumigatus requires a
carbon catabolite repression (CCR) mediated genetic network to support in vivo
fungal fitness and disease progression. While CCR as mediated by the
transcriptional repressor CreA is not required for pulmonary infection
establishment, loss of CCR inhibits fungal metabolic plasticity and the ability
to thrive in the dynamic infection microenvironment. Our results suggest a model
whereby CCR in an environmental filamentous fungus is dispensable for initiation
of pulmonary infection but essential for infection maintenance and disease
progression. Conceptually, we argue these data provide a foundation for
additional studies on fungal factors required to support fungal fitness and
disease progression and term such genes and factors, DPFs (disease progression
factors).
PMID- 28423063
TI - Vitamin D status and its association with insulin resistance among type 2
diabetics: A case -control study in Ghana.
AB - BACKGROUND: Vitamin D plays a major role in physiological processes that modulate
mineral metabolism and immune function with probable link to several chronic and
infectious conditions. Emerging data suggests a possible influence of vitamin D
on glucose homeostasis. This study sought to provide preliminary information on
vitamin D status among Ghanaian type 2 diabetics and assessed its association
with glucose homeostasis. METHODS: In a case control study, 118 clinically
diagnosed Type 2 Diabetes Mellitus (T2DM) patients attending Diabetic Clinic at
the Nkawie Government Hospital were enrolled between October and December 2015.
Hundred healthy non-diabetics living in Nkawie district were selected as
controls. Structured questionnaires were administered to obtain socio-demographic
data. Venous blood samples were taken from both cases and controls to estimate
their FBG, Lipid profile spectrophotometrically and IPTH, 25OHD by ELISA.
Statistical analyses were performed using SPSS v20.0 Statistics. RESULTS: The
average age of the study participants was 58.81years for cases and 57.79year for
controls. There was vitamin D deficiency of 92.4% among T2DM cases and 60.2%
among the non diabetic controls. Vitamin D deficiency did not significantly
associate with HOMA-beta [T2DM: r2 = 0.0209, p = 0.1338 and Control: r2 = 0.0213,
p = 0.2703] and HOMA-IR [T2DM: r2 = 0.0233, p = 0.1132 and Control: r2 = 0.0214,
p = 0.2690] in both the controls and the cases. CONCLUSION: Vitamin D deficiency
is prevalent in both T2DM and non-diabetics. There is no association between
vitamin D deficiency and insulin resistance or beta cell function in our study
population. Vitamin D supplementation among type 2 diabetics is recommended.
PMID- 28423066
TI - Influence of maternal anxiety on child anxiety during dental care: cross
sectional study.
AB - CONTEXT AND OBJECTIVES:: Anxiety is usually classified as a disorder of neurotic
nature and is often related to contexts of stress, which may include worries,
motor tension and autonomic hyperactivity. The aim of this study was to assess
the influence of mothers' anxiety on their children's anxiety during dental care.
DESIGN AND SETTING:: Analytical cross-sectional study conducted at in a private
dentistry school in the south of Brazil. METHODS:: Convenience sampling was used.
All mothers of children undergoing treatment were invited to participate in this
study. Data to investigate anxiety related to dental treatment among the children
were collected through applying the Venham Picture Test (VPT) scale. For the
mothers, the Corah scale was applied. A self-administered sociodemographic
questionnaire with questions about demographic, behavioral, oral health and
dental service variables was also used. RESULTS:: 40 mother-child pairs were
included in the study. The results showed that 40% of the children were anxious
and 60% of the mothers were slightly anxious. Local anesthesia was the procedure
that caused most anxiety among the mothers, making them somewhat uncomfortable
and anxious (60%). Family income higher than R$ 1,577.00 had an influence on
maternal anxiety (75.6%). Maternal anxiety had an influence on child anxiety
(81.3%). CONCLUSION:: Most of the children showed the presence of anxiety, which
ranged from fear of dental care to panic, inferring that maternal anxiety has an
influence on children's anxiety. Dental procedures did not interfere with the
mothers' anxiety, but caused positive feelings, whereas they affected the
children more.
PMID- 28423064
TI - Biochemical evaluation of the anticancer potential of the polyamine-based
nanocarrier Nano11047.
AB - Synthesizing polycationic polymers directly from existing drugs overcomes the
drug-loading limitations often associated with pharmacologically inert
nanocarriers. We recently described nanocarriers formed from a first-generation
polyamine analogue, bis(ethyl)norspermine (BENSpm), that could simultaneously
target polyamine metabolism while delivering therapeutic nucleic acids. In the
current study, we describe the synthesis and evaluation of self-immolative
nanocarriers derived from the second-generation polyamine analogue PG-11047.
Polyamines are absolutely essential for proliferation and their metabolism is
frequently dysregulated in cancer. Through its effects on polyamine metabolism,
PG-11047 effectively inhibits tumor growth in cancer cell lines of multiple
origins as well as in human tumor mouse xenografts. Promising clinical trials
have been completed verifying the safety and tolerance of this rotationally
restricted polyamine analogue. We therefore used PG-11047 as the basis for
Nano11047, a biodegradable, prodrug nanocarrier capable of targeting polyamine
metabolism. Following exposure of lung cancer cell lines to Nano11047, uptake and
intracellular degradation into the parent compound PG-11047 was observed. The
release of PG-11047 highly induced the polyamine catabolic enzyme activities of
spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). By
contrast, the activity of ornithine decarboxylase (ODC), a rate-limiting enzyme
in polyamine biosynthesis and a putative oncogene, was decreased. Consequently,
intracellular levels of the natural polyamines were depleted concurrent with
tumor cell growth inhibition. This availability of Nano11047 as a novel drug form
and potential nucleic acid delivery vector will potentially benefit and encourage
future clinical studies.
PMID- 28423065
TI - Association of body mass index with clinical outcomes for in-hospital cardiac
arrest adult patients following extracorporeal cardiopulmonary resuscitation.
AB - BACKGROUND: Obesity might be associated with disturbance of cannulation in
situation of extracorporeal cardiopulmonary resuscitation (ECPR). However,
limited data are available on obesity in the setting of ECPR. Therefore, we
investigated the association between body mass index (BMI) and clinical outcome
in patients underwent ECPR. METHODS: From January 2004 to December 2013, in
hospital cardiac arrest patients who had ECPR were enrolled from a single-center
registry. We divided patients into four group according to BMI defined with the
WHO classification (underweight, BMI < 18.5, n = 14; normal weight, BMI = 18.5
24.9, n = 118; overweight, BMI = 25.0-29.9, n = 53; obese, BMI >= 30, n = 15).
The primary outcome was survival to hospital discharge. RESULTS: Analysis was
carried out for a total of 200 adult patients (39.5% females). Their median BMI
was 23.20 (interquartile range, 20.93-25.80). The rate of survival to hospital
discharge was 31.0%. There was no significant difference in survival to hospital
discharge among the four groups (underweight, 35.7%; normal, 31.4%; overweight,
30.2%; obese, 26.7%, p = 0.958). Neurologic outcomes (p = 0.85) and procedural
complications (p = 0.40) were not significantly different among the four groups
either. SOFA score, initial arrest rhythm, and CPR to extracorporeal membrane
oxygenation (ECMO) pump on time were significant predictors for survival to
discharge, but not BMI. CONCLUSION: BMI was not associated with in-hospital
mortality who underwent ECPR. Neurologic outcomes at discharge or procedural
complications following ECPR were not related with BMI either.
PMID- 28423067
TI - Isospora albicollis (Apicomplexa: Eimeriidae) in thrushes Turdus spp.
(Passeriformes: Turdidae), in southeastern Brazil.
AB - The aim of the present study was to report and describe Isospora albicollis
Lainson and Shaw, 1989 parasitizing a white-necked thrush Turdus albicollis
Vieillot, 1818 and a pale-breasted thrush Turdus leucomelas Vieillot, 1818 in two
different localities: the Itatiaia National Park and Cacaria, in southeastern
Brazil. The oocysts identified were ovoidal, 24.4 * 19.7 MUm, with a smooth,
bilayered wall, around 1.4 MUm thick. Oocyst residuum was absent, but a micropyle
and a polar granule were present. The sporocysts were ellipsoidal, 15.4 * 10.1
MUm. The Stieda body was knob-like to rounded and the sub-Stieda body was
prominent and wide. Sporocyst residuum was present, usually as a cluster of
granules that appear to be membrane-bounded. The sporozoites were vermiform with
one posterior refractile body and a centrally located nucleus. Besides recording
the new host T. leucomelas, the identification of I. albicollis in the Itatiaia
National Park and Cacaria, in southeastern Brazil, provide records of new
localities for its parasitism, and reveals the wide distribution and dispersion
of this coccidium in Brazil.
PMID- 28423068
TI - Suicide and meteorological factors in Sao Paulo, Brazil, 1996-2011: a time series
analysis.
AB - Objective:: Considering the scarcity of reports from intertropical latitudes and
the Southern Hemisphere, we aimed to examine the association between
meteorological factors and suicide in Sao Paulo. Method:: Weekly suicide records
stratified by sex were gathered. Weekly averages for minimum, mean, and maximum
temperature ( degrees C), insolation (hours), irradiation (MJ/m2), relative
humidity (%), atmospheric pressure (mmHg), and rainfall (mm) were computed. The
time structures of explanatory variables were modeled by polynomial distributed
lag applied to the generalized additive model. The model controlled for long-term
trends and selected meteorological factors. Results:: The total number of
suicides was 6,600 (5,073 for men), an average of 6.7 suicides per week (8.7 for
men and 2.0 for women). For overall suicides and among men, effects were
predominantly acute and statistically significant only at lag 0. Weekly average
minimum temperature had the greatest effect on suicide; there was a 2.28%
increase (95%CI 0.90-3.69) in total suicides and a 2.37% increase (95%CI 0.82
3.96) among male suicides with each 1 degrees C increase. Conclusion:: This
study suggests that an increase in weekly average minimum temperature has a short
term effect on suicide in Sao Paulo.
PMID- 28423069
TI - Trypophobia: an investigation of clinical features.
AB - OBJECTIVE: Trypophobia refers to the fear of, or aversion to, clusters of holes.
We assessed clinical features of trypophobia and investigated whether it most
resembled a specific phobia or obsessive-compulsive disorder. METHODS: An online
survey was conducted to gather information on sociodemographic variables, course
and duration, severity, associated features, comorbid psychiatric diagnoses, and
levels of psychological distress and impairment in individuals with trypophobia.
The survey also explored whether such individuals experienced more fear or
disgust, and whether symptoms showed more resemblance to a specific phobia or to
obsessive-compulsive disorder. Associations of symptom severity and duration with
degree of impairment were investigated. RESULTS: One hundred and ninety-five
individuals completed the questionnaire. Symptoms were chronic and persistent.
The most common associated comorbidities were major depressive disorder and
generalized anxiety disorder. Trypophobia was associated with significant
psychological distress and impairment. The majority of individuals experienced
disgust rather than fear when confronted with clusters of holes, but were more
likely to meet DSM-5 criteria for specific phobia than for obsessive-compulsive
disorder. Symptom severity and duration were associated with functional
impairment. CONCLUSIONS: Given that individuals with trypophobia suffer
clinically significant morbidity and comorbidity, this condition deserves further
attention from clinicians and researchers.
PMID- 28423070
TI - The Extended Log-Logistic Distribution: Properties and Application.
AB - We propose a new four-parameter lifetime model, called the extended log-logistic
distribution, to generalize the two-parameter log-logistic model. The new model
is quite flexible to analyze positive data. We provide some mathematical
properties including explicit expressions for the ordinary and incomplete
moments, probability weighted moments, mean deviations, quantile function and
entropy measure. The estimation of the model parameters is performed by maximum
likelihood using the BFGS algorithm. The flexibility of the new model is
illustrated by means of an application to a real data set. We hope that the new
distribution will serve as an alternative model to other useful distributions for
modeling positive real data in many areas.
PMID- 28423072
TI - Editors of Brazilian journals - a hard life that is getting harder!
PMID- 28423071
TI - On topological groups with an approximate fixed point property.
AB - A topological group G has the Approximate Fixed Point (AFP) property on a bounded
convex subset C of a locally convex space if every continuous affine action of G
on C admits a net ( x i ) , x i ? C , such that x i - g ? x i ? 0 for all g ? G .
In this work, we study the relationship between this property and amenability.
PMID- 28423073
TI - Purification of inulinases by changing the ionic strength of the medium and
precipitation with alcohols.
AB - The present study evaluated the purification of inulinase by changing the ionic
strength of the medium by addition of NaCl and CaCl2 followed by precipitation
with n-propyl alcohol or iso-propyl alcohol. The effects of the concentration of
alcohols and the rate of addition of alcohols in the crude extract on the
purification yield and purification factor were evaluated. Precipitation caused
an activation of enzyme and allowed purification factors up to 2.4-fold for both
alcohols. The purification factor was affected positively by the modification of
the ionic strength of the medium to 0.5 mol.L-1 NaCl before precipitation with
the alcohol (n-propyl or iso-propyl). A purification factor of 4.8-fold and an
enzyme yield of 78.1 % could be achieved by the addition of 0.5 mol.L-1 of NaCl
to the crude extract, followed by the precipitation with 50 % (v/v) of n-propyl
alcohol, added at a flow rate of 19.9 mL/min.
PMID- 28423074
TI - 7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C
chemical shift assignments.
AB - A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a
and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The
structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and
spectral comparison with related compounds, leading to complete assignment of the
1H and 13C NMR spectra.
PMID- 28423075
TI - Glass Microbeads in Analog Models of Thrust Wedges.
AB - Glass microbeads are frequently used in analog physical modeling to simulate weak
detachment zones but have been neglected in models of thrust wedges. Microbeads
differ from quartz sand in grain shape and in low angle of internal friction. In
this study, we compared the structural characteristics of microbeads and sand
wedges. To obtain a better picture of their mechanical behavior, we determined
the physical and frictional properties of microbeads using polarizing and
scanning electron microscopy and ring-shear tests, respectively. We built
shortening experiments with different basal frictions and measured the thickness,
slope and length of the wedges and also the fault spacings. All the microbeads
experiments revealed wedge geometries that were consistent with previous studies
that have been performed with sand. However, the deformation features in the
microbeads shortened over low to intermediate basal frictions were slightly
different. Microbeads produced different fault geometries than sand as well as a
different grain flow. In addition, they produced slip on minor faults, which was
associated with distributed deformation and gave the microbeads wedges the
appearance of disharmonic folds. We concluded that the glass microbeads may be
used to simulate relatively competent rocks, like carbonates, which may be
characterized by small-scale deformation features.
PMID- 28423076
TI - Transmissivity of Aquifer by Capture Zone Method: An Application in the Sete
Lagoas Karst Aquifer, MG, Brazil.
AB - Transmissivity is an important hydraulic parameter to determine the amount of
water passed horizontally across a given saturated thickness of an aquifer. The
techniques to quantify this parameter, such as grain size analyses or pumping
tests, can have limitations of time/spatial scale, viability, or economically.
One technique that can be used, but little adopted, is the capture zone analysis.
In this paper, capture zone analytical equations were used to estimate
transmissivity values in order to verify the effectiveness of this methodology as
alternative in situations where other traditional methods present implementation
difficulties. The results were compared with field data estimated by aquifer
tests conducted in the same region. A sensitivity analysis was also performed to
identify possible discrepancies between the analytical and field data results.
The aquifer studied was the Sete Lagoas Karst Aquifer in the urban region of the
municipality of Sete Lagoas, Brazil. The method proved to be a viable and
economical tool, where the analytical values compared to the aquifer tests showed
similarities, being confirmed by a sensitivity analysis. However, a reliable
potentiometric surface map, which enables the identification of the parameters
for analytical capture zone equations, is needed.
PMID- 28423077
TI - Early Devonian (Late Emsian) shark fin remains (Chondrichthyes) from the Parana
Basin, southern Brazil.
AB - We report on the pioneering discovery of Devonian fish remains in the Parana
Basin, which represents the southernmost record of fishes from that period in
mainland South America. The material comes from an outcrop at the lower portion
of the Sao Domingos Formation, within Sequence C of the Parana-Apucarana sub
basin in Tibagi, State of Parana. Marine invertebrates are abundant in the same
strata. The dark colored fish remains were collected in situ and represent
natural moulds of partially articulated shark fin rays (radials). No elements
such as teeth or prismatic cartilage have been preserved with the fins rays. This
can be attributed to the dissolution of calcium-phosphatic minerals at the early
stages of fossilization due to diagenetic processes possibly linked to strong
negative taphonomic bias. This may have contributed to the fact that fishes
remained elusive in the Devonian strata of this basin, despite substantial
geological work done in the Parana State in recent decades. In addition, the
scarcity of fish fossils may be explained by the fact that the Devonian rock
deposits in this basin originated in a vertebrate impoverished, cold marine
environment of the Malvinokaffric Realm, as previously suspected.
PMID- 28423078
TI - Characterization and bioactivities of a novel polysaccharide obtained from
Gracilariopsis lemaneiformis.
AB - Gracilariopsis lemaneiformis is a type of red alga that contains seaweed
polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide
fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis
lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural
analysis showed that GCP shows triple helical chain conformation when dissolved
in water and has many branches and long side chains. Also, 1->3 linkage is the
major linkage and the sugar structures are galactopyranose configurations linked
by beta-type glycosidic linkages. Two macromolecular substance fractions (GCP-1
and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography.
Moreover, a splenocyte damage assay and splenocyte proliferation assay were used
to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that
polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest
protection rate, that is, 92.8%, which significantly enhanced the splenocyte
proliferation, and GCP showed the highest proliferation rate, 9.30%. The results
suggested that this type of novel non-agar polysaccharide displayed remarkable
antioxidant and immunomodulatory activities and early alkali treatment could
decrease the activities. It may represent a potential material for health food
and clinical medicines.
PMID- 28423079
TI - The partitioning of food resources between two rodents in the subtropical region
of southern Brazil.
AB - The capybara (Hydrochoerus hydrochaeris) and nutria (Myocastor coypus) are
herbivorous semi-aquatic rodents. Although these rodents occur in sympatry in
southern South America, little is known about how the two species interact in
relationship to food resources. In this context, the aim of this study was to
analyze the food resource overlap, the feeding strategy and the diversity of the
diet of capybaras and nutria. A micro-histological analysis of feces was used to
study the diets. A total of 48 plant species belonging to 10 families were
identified in the diet of H. hydrochaeris, and a total of 49 species belonging to
14 families were identified in the diet of M. coypus. According to the Amundsen
graphical method, both rodents adopted a specialized strategy for feeding on
Poaceae and a generalized strategy for other families. The results of a
multivariate analysis of the dietary data showed significant differences between
the two rodent species and among the seasons. These differences between diets may
be related to the different proportions of each food item eaten. However, the
dietary overlap between the two rodents in the Taim wetland was high, suggesting
that partitioning of other resources ensured the coexistence of the species.
PMID- 28423080
TI - S-(+)- and R-(-)-linalool: a comparison of the in vitro anti-Aeromonas hydrophila
activity and anesthetic properties in fish.
AB - Linalool is the main compound of many essential oils and occurs in two isomeric
forms: S-(+)- and R-(-)-linalool. This study aimed to determine if linalool
isomers have different antimicrobial and anesthetic properties in fish. For this
purpose, these compounds were previously isolated from Lippia alba (Mill.)N. E.
Brown and Ocimum americanum L. essential oils. Antimicrobial effects were
evaluated through the microdilution test against Aeromonas hydrophila, an
important fish disease etiologic agent. Induction time until sedation, anesthesia
and recovery time were determined in silver catfish (Rhamdia quelen) through bath
exposure (60, 180, 300 or 500 MUL L-1). The results showed different biological
properties for the isomers being S-(+)-linalool the only active against A.
hydrophila at 3.2 mg mL-1. The sedation was induced without differences between
the compounds, however R-(-)-linalool promoted faster anesthesia. There were no
differences regarding the recovery time of the animals exposed to the linalool
isomers. Although both S-(+)- and R-(-)-linalool can be used for sedative
purposes, their use in A. hydrophila infection is inadvisable due to the high
effective concentration. Considering anesthesia as the main objective, the R-(-)
linalool demonstrated clear advantages at lower concentration.
PMID- 28423081
TI - Long-wavelength sensitive opsin (LWS) gene variability in Neotropical cichlids
(Teleostei: Cichlidae).
AB - Cichlid fishes are an important group in evolutionary biology due to their fast
speciation. This group depends widely of vision for feeding and reproduction.
During the evolutionary process it plays a significant role in interspecific and
intraspecific recognition and in its ecology. The molecular basis of vision is
formed by the interaction of the protein opsin and retinal chromophore. Long
wavelength sensitive opsin (LWS) gene is the most variable among the opsin genes
and it has an ecological significance. Current assay identifies interspecific
variation of Neotropical cichlids that would modify the spectral properties of
the LWS opsin protein and codons selected. Neotropical species present more
variable sites for LWS gene than those of the African lakes species. The LWS
opsin gene in Crenicichla britskii has a higher amino acid similarity when
compared to that in the African species, but the variable regions do not overlap.
Neotropical cichlids accumulate larger amounts of variable sites for LWS opsin
gene, probably because they are spread over a wider area and submitted to a wider
range of selective pressures by inhabiting mainly lotic environments.
Furthermore, the codons under selection are different when compared to those of
the African cichlids.
PMID- 28423082
TI - Comparative analysis of two different models of swimming applied to pregnant rats
born small for pregnant age.
AB - The aim of this study was to compare two models of swimming applied to pregnant
rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult
female rats to develop an inadequate intrauterine environment, leading to birth
of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to
different swimming programs. The exercise program 1 (Ex1) consisted of swimming
for 15 minutes, followed by 15 minutes of rest and another 15 minutes of
swimming, 3 days a week before and during pregnancy. Another program (Ex2) was
applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The
pregnant rats presented no interference on body weight and glycemia. The rats
submitted to Ex2 model showed decreased insulin and blood glucose levels by oral
glucose tolerance test, and reduction in area under curve values. The offspring
from dams submitted to both exercise protocols presented an increased rate of
newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher
of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of
60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth
restricted females. However, this protocol employed at pregnancy leads to
intrauterine growth restriction.
PMID- 28423083
TI - Autophagy protects against neural cell death induced by piperidine alkaloids
present in Prosopis juliflora (Mesquite).
AB - Prosopis juliflora is a shrub that has been used to feed animals and humans.
However, a synergistic action of piperidine alkaloids has been suggested to be
responsible for neurotoxic damage observed in animals. We investigated the
involvement of programmed cell death (PCD) and autophagy on the mechanism of cell
death induced by a total extract (TAE) of alkaloids and fraction (F32) from P.
juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial
cell co-culture. We saw that TAE (30 ug/mL) and F32 (7.5 ug/mL) induced reduction
in ATP levels and changes in mitochondrial membrane potential at 12 h exposure.
Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and
neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized
by decreases of P62 protein level, increase of LC3II expression and increase in
number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of
autophagy by bafilomycin and vinblastine increased the cell death induced by TAE
and autophagy induced by serum deprivation and rapamycin reduced cell death
induced by F32 at 24 h. These results indicate that the mechanism neural cell
death induced by these alkaloids involves PCD via caspase-9 activation and
autophagy, which seems to be an important protective mechanism.
PMID- 28423084
TI - Immune System Dysfunction in the Elderly.
AB - Human aging is characterized by both physical and physiological frailty that
profoundly affects the immune system. In this context aging is associated with
declines in adaptive and innate immunity established as immunosenescence.
Immunosenescence is a new concept that reflects the age-associated restructuring
changes of innate and adaptive immune functions. Thus elderly individuals usually
present chronic low-level inflammation, higher infection rates and chronic
diseases. A study of alterations in the immune system during aging could provide
a potentially useful biomarker for the evaluation of immune senescence treatment.
The immune system is the result of the interplay between innate and adaptive
immunity, yet the impact of aging on this function is unclear. In this article
the function of the immune system during aging is explored.
PMID- 28423085
TI - Molecular survey of Anaplasma platys and Ehrlichia canis in dogs from Campo
Grande, Mato Grosso do Sul, Brazil.
AB - This study investigated the frequency of infection by Anaplasma platys and
Ehrlichia canis in dogs submitted to animal health centers in Campo Grande, state
of Mato Grosso do Sul, Brazil. E. canis and A. platys showed infection
frequencies of 55.75% and 16.96%, respectively. The identity of the two species
was confirmed by DNA sequencing.
PMID- 28423086
TI - Evaluation of cytogenotoxicity, antioxidant and hypoglycemiant activities of
isolate compounds from Mansoa hirsuta D.C. (Bignoniaceae).
AB - Mansoa hirsuta (Bignoniaceae) is a native plant from caatinga in Brazilian
semiarid. This plant has been locally used as antimicrobial and hypoglycemiant
agents, but their action mechanisms and toxicity remain largely unknown.
Therefore, we evaluated the composition and antioxidant, cytoprotective and
hypoglycemiant effects of raw extract, fractions and compounds from leaves of M.
hirsuta. The cytogenotoxic effects of ursolic and oleanolic acids, the main
phytotherapic components of this plant, were assessed. The raw extract and
fractions presented steroids, saponins, flavonols, flavanonols, flavanones,
xanthones, phenols, tannins, anthocyanins, anthocyanidins and flavonoids. The
ethyl acetate fraction inhibited efficiently the cascade of lipid peroxidation
while the hydroalcoholic fraction was richer in total phenols and more efficient
in capturing 2,2-diphenyl-1-picrylhydrazyl (.DPPH) and 2,2'-azino-bis (3
ethylbenzthiazoline-6-sulfonic acid) (ABTS.+) radicals. The isolated fraction of
M. hirsuta also inhibited the alpha-amylase activity. Cytotoxic effects were
absent in both raw extract and fractions while ursolic+oleanolic acids were
efficient in protecting cells after exposure to hydrogen peroxide. Moreover, this
mixture of acid shad no significant interference on the mitotic index and
frequency of nuclear and/or chromosomal abnormalities in Allium cepa test.
Therefore, M. hirsuta represents a potential source of phytochemicals against
inflammatory and oxidative pathologies, including diabetes.
PMID- 28423087
TI - Epidemiological aspects of American cutaneous leishmaniasis (ACL) in an endemic
area of forest extractivist culture in western Brazilian Amazonia.
AB - The study sought to analyze clinical and epidemiological aspects of cutaneous
leishmaniasis (CL) in Xapuri, Acre, Brazil. Data from 2008 to 2014 registered in
the notification records of the disease of the Information System of the
Complaints of Notification (SINAN), and the data of the Information Department of
the Unified Health System (DATASUS) available from 2007 to 2013 were used and
analyzed in the light of the statistics of the temporal series by the Prais
Winsten method and chi-squared test. A total of 906 cases were registered with
60.2% occurring in men and 39.7% in women. The groups from 0 to 4 years of age
(48.0%) and from 5 to 19 years of age (23.3%) were the most affected. Regarding
the clinical forms, 77.7% presented CL and 22.3% mucocutaneous leishmaniasis
(MCL). Among the 896 cases with information on the diagnostic methods used,
Montenegro's skin test predominated (66.4%), with a positive result of 95.8% for
CL and 99.3% for MCL. Treatment with N-methylglucamine antimony was performed in
99.4% of the cases, but discontinuously used in the majority of patients. This
study presents information which may be used as a tool for the epidemiological
surveillance and control of the disease in Xapuri, a region which depends
essentially on forest resources and ecological tourism.
PMID- 28423088
TI - The epidemiology of cryptococcosis and the characterization of Cryptococcus
neoformans isolated in a Brazilian University Hospital.
AB - Cryptococcosis, a systemic disease caused by the fungus Cryptococcus neoformans/
Cryptococcus gattii is more severe in immunocompromised individuals. This study
aimed to analyze the epidemiology of the disease, the molecular characteristics
and the antifungal susceptibility of C. neoformans isolated from patients treated
in a Brazilian university hospital. This retrospective study was conducted in the
Clinical Hospital, Federal University of Uberlandia, and evaluated cases of
cryptococcosis and strains of C. neoformans isolated from 2004 to 2013. We
evaluated 41 patients, 85% of whom were diagnosed with AIDS. The fungus was
isolated from the cerebrospinal fluid (CSF) of 21 patients (51%); 19.5% had
fungemia and in 24% the agent was isolated from the CSF and blood, concurrently.
Meningoencephalitis was the most frequent (75%) manifestation of infection.
Despite adequate treatment, the mortality of the disease was 58.5%. Most isolates
(97.5%) presented the VNI genotype (serotype A, var. grubii) and one isolate was
genotyped as C. gattii (VGI); all the isolates were determined as mating type
MATa and showed susceptibility to the tested antifungals (fluconazole,
voriconazole, amphotericin B and 5-flucytosine). Although AIDS detection rates
remain stable, opportunistic infections such as cryptococcosis remain as major
causes of morbidity and mortality in these patients.
PMID- 28423089
TI - Phenotypic and genotypic detection of Candida albicans and Candida dubliniensis
strains isolated from oral mucosa of AIDS pediatric patients.
AB - The aim of this study was to assess a collection of yeasts to verify the presence
of Candida dubliniensis among strains isolated from the oral mucosa of AIDS
pediatric patients which were initially characterized as Candida albicans by the
traditional phenotypic method, as well as to evaluate the main phenotypic methods
used in the discrimination between the two species and confirm the identification
through genotypic techniques, i.e., DNA sequencing. Twenty-nine samples of C.
albicans isolated from this population and kept in a fungi collection were
evaluated and re-characterized. In order to differentiate the two species,
phenotypic tests (Thermotolerance tests, Chromogenic medium, Staib agar, Tobacco
agar, Hypertonic medium) were performed and genotypic techniques using DNA
sequencing were employed for confirmation of isolated species. Susceptibility and
specificity were calculated for each test. No phenotypic test alone was
sufficient to provide definitive identification of C. dubliniensis or C.
albicans, as opposed to results of molecular tests. After amplification and
sequencing of specific regions of the 29 studied strains, 93.1% of the isolates
were identified as C. albicans and 6.9% as C. dubliniensis. The Staib agar assay
showed a higher susceptibility (96.3%) in comparison with other phenotypic
techniques. Therefore, genotypic methods are indispensable for the conclusive
identification and differentiation between these species.
PMID- 28423090
TI - Scientometrics of zoonoses transmitted by the giant African snail Achatina fulica
Bowdich, 1822.
AB - The dissemination of the giant African snail Achatina fulica in several countries
has triggered a great number of studies on the mollusk, including those on
zoonoses related to health in humans. The current research is a scientific survey
on articles published in four databases, namely, PubMed, Bireme, Scielo and
Lilacs. Results indicate that Brazil has a prominent position in international
scientific production on this subject, with focus on Angiostrongylus cantonensis
occurrences.
PMID- 28423091
TI - An unusual abdominal wall mass in a child.
AB - Abdominal tumors are one of the most common types of pediatric cancer. Therefore,
they should always be included in the differential diagnosis of abdominal masses.
Here, we present the case of a child whose initial hypothesis of diagnosis
contemplated this possibility. Later, it was demonstrated that the abdominal mass
found was secondary to a common parasitosis. A 2-year old, moderately
malnourished and pale white boy was referred with a history of a rapidly growing,
well-limited, middle abdominal mass. The mass was 10 by 3 cm, hard and poorly
movable, apparently involving both abdominal rectus muscles. A complete resection
was performed, revealing an abdominal wall abscess, with intense eosinophilic
proliferation, secondary to a local and intense reaction to innumerous Ascaris
lumbricoides eggs. Extra luminal infestations with Ascaris, that usually form
peritoneal granulomas have been previously described. However, neither external
trauma nor fistula, that could explain the superficial presence of the eggs, was
found. This description reinforces the relevance of infectious diseases within
the differential diagnosis of abdominal masses, particularly in areas with high
prevalence of parasitic infestations.
PMID- 28423092
TI - What to expect from the 2017 yellow fever outbreak in Brazil?
PMID- 28423093
TI - Short and long term evaluation of the efficiency of PermaNet(r) 2.0 bed net
against environmental factors and washing using bioassay tests.
AB - The aim of the present study was to examine the resistance of PermaNet(r) 2.0 bed
nets against repeated washing and environmental factors by using bioassay tests.
After 5, 15 and 21 washings with detergents and by using bioassay tests, the
resistance of 40 PermaNet(r) 2.0 bed nets was compared with that of 40 bed nets
conventionally treated with one K-O tablet. To examine the long-term resistance,
31 PermaNet(r) 2.0 bed nets were also distributed among villagers, and were re
collected to perform bioassay tests after 1, 2 and 5 years. In the first phase of
this study, the insecticidal effect of the conventionally-treated nets
significantly decreased due to repeated washings (P < 0.001); however, it was not
significant regarding PermaNet(r) 2.0 bed nets (P = 0.92 in continuous exposure
and P = 0.12 in mortality tests). In the long-term phase of this study, the time
required for knockdown of PermaNet(r) 2.0 increased over the first 2 years and
then decreased. In addition, the mortality rate decreased over the first 2 years
and then increased. In conclusion, it seems that the technique used by the
manufacturer for impregnation of PermaNet(r) 2.0 bed nets has an acceptable
efficiency in comparison with conventional techniques.
PMID- 28423094
TI - Complications of chronic necrotizing pulmonary aspergillosis: review of published
case reports.
AB - Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary
aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons
with underlying pulmonary disease. These conditions are associated with high
morbidity and mortality and often require long-term antifungal treatment. The
long-term prognosis for patients with CNPA and the potential complications of
CNPA have not been well documented. The aim of this study was to review published
papers that report cases of CNPA complications and to highlight risk factors for
development of CNPA. The complications in conjunction associated with CNPA are as
follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing
spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome,
pulmonary Mycobacterium avium complex (MAC) disease, superinfection with
Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still
a challenge. Culture and histologic examinations of bronchoscopically identified
tracheobronchial mucus plugs and necrotic material should be performed in all
immunocompromised individuals, even when the radiographic findings are unchanged.
Early detection of intraluminal growth of Aspergillus and prompt antifungal
therapy may facilitate the management of these patients and prevent development
of complications.
PMID- 28423095
TI - First reported case of fulminant TB with progression of infection from lungs to
the genitourinary region.
AB - Although tuberculosis (TB) is a curable disease, it continues to be one of the
leading infections associated with death in the world. Extra-pulmonary TB (EPTB)
occurs in approximately 10% of the total cases, presenting with lymph nodes,
pleura, bone and genitourinary tract as the most common locations. Genitourinary
tuberculosis, the second most common EPTB, is very difficult to diagnose unless
there is a high index of suspicion. Isolated TB orchitis or prostatitis without
clinical evidence of renal involvement is a rare entity among genitourinary
tuberculosis. We presented the first reported case of TB prostatitis and orchitis
associated with pulmonary TB and the presence of an acute massive caseous
pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient
presented a rapid progression of disease and deterioration of general conditions
taking to death, which occurred four days after TB treatment had started.
Disseminated TB is a relatively uncommon cause of acute massive caseous
pneumonia; however, there should always be suspicion of the disease, since it is
a potentially treatable cause. This rare case supports the assertion that TB
should be considered as an important differential diagnosis of genitourinary
tumors irrespective of evidence of active TB elsewhere in the body.
PMID- 28423096
TI - Perspectives on the Zika outbreak: herd immunity, antibody-dependent enhancement
and vaccine.
PMID- 28423097
TI - Guillain-Barre syndrome and dengue-like disease in 2015: temporal relationship in
Piaui state and implications on Zika virus surveillance.
PMID- 28423098
TI - ?
PMID- 28423099
TI - ?
PMID- 28423100
TI - ?
PMID- 28423101
TI - ?
PMID- 28423102
TI - ?
PMID- 28423103
TI - ?
PMID- 28423104
TI - ?
PMID- 28423105
TI - [Adolescense pregnancy in a marginalized rural community in Mexico].
AB - Objective:: To identify objective and subjective conditions in the lives of
pregnant teens within a highly-marginalized community in the state of Puebla,
Mexico. Materials and methods:: Objective and subjective conditions of pregnant
teens were evaluated through a mixed methodology (surveys, observation guides and
a structured interview guide). Results:: The main family characteristic is the
absence of a father due to migration, no desire to study or work and the new
meaning of pregnancy: the initial social stigma for engaging in a sexual activity
and then, the stigma for being a young mother. Conclusions:: Objective conditions
show family disintegration, lack of access to education at the community, high
school and college level as well as unemployment as processes linked to teen
pregnancy; thus, making it practically impossible to develop life goals.
Subjective conditions center around the reproduction of gender stereotypes
related to maternity.
PMID- 28423106
TI - [Comprehensive sexual education in Mexico: an analysis of coverage,
comprehensiveness and continuity of contents in Mexican public and private
schools].
AB - Objective:: To analyze coverage of comprehensive sex education (CSE) in high
schools in Mexico and describe whether it is comprehensive, homogeneous and has
continuity based on student reports of exposure to topics in three dimensions:
reproductive and sexual health, self-efficacy and rights and relations. Materials
and methods:: Within a probabilistic, cross-sectional survey with stratified,
cluster sampling, a nationally representative sample of 3 824 adolescents
attending 45 public and private high-schools in urban and rural areas completed
questionnaires on CSE. Results:: The proportion of adolescents reporting having
received sex education from school personnel varies depending on topics and grade
level. Topics most frequently covered are those related to sexual and
reproductive health while rights and relations are least frequently dealt with.
Most sex education topics are covered during junior high school and much less
frequently in elementary or high school. Conclusions:: CSE needs to be
comprehensive and homogenous in terms of content, ensure inclusion of priority
topics, meet national and international recommendations, ensure continuity and
adapt contents to student age through all education levels.
PMID- 28423107
TI - Health program in a Brazilian school.
AB - Objective:: To analyze the School Health Program (SHP) through the perceptions of
managers and health professionals. Materials and methods:: This was a
descriptive, cross-sectional, and qualitative study that conducted interviews
with 21 individuals using the lexical analysis of Bardin's speech and processed
the data through the Alceste software. Results:: In the interviewees' perception,
verification of blood pressure, visual acuity, weight, height, body mass index,
oral health, preventive actions and educational lectures are recommended in the
program's guidelines. The schools do not have available and adequate space for
the staff to perform the work. The predominant exchange occurs between the health
and education secretaries. The actions that provided opportunities to students
were primarily promotion, prevention, and health education; funding is the
responsibility of the Ministry of Health and Municipal Secretary of Health.
Conclusions:: The structures, exchanges, and available resources were
insufficient for the development of the program.
PMID- 28423108
TI - [Potential health risks from consumption of water with arsenic in Colima,
Mexico].
AB - Objective:: To estimate potential health risks due to chronic ingestion of
arsenic from groundwater in Colima, Mexico. Materials and methods:: Samples were
randomly taken in 36 wells from 10 local aquifers. Analysis was performed by ICP
OES following international standards. Geostatistical interpolation was performed
with ArcGIS, implementing a model weighting inverse distance to estimate arsenic
routes of exposure and consumption on each locality. The Hazard Quotient Ratio
(HQ) and carcinogenic risk (R) for As were estimated. Results:: The weighted
average HQ for arsenic in Colima is 2.41. There are HQ> 1 values indicating
adverse non-cancer health effects by continuous and prolonged intake of water
with arsenic, which could affect 183 832 individuals in the state. The risk of
developing any type of cancer among the population in this study due to high
arsenic concentrations in groundwater (R) is 1.089E-3, which could statistically
cause 446 cases of cancer. Conclusions:: Current levels of arsenic in groundwater
increase carcinogenic and non-carcinogenic human health risks in Colima.
PMID- 28423109
TI - Effects of climatic and social factors on dengue incidence in Mexican
municipalities in the state of Veracruz.
AB - Objective:: To assess links between the social variables and longer-term El Nino
Southern Oscillation (ENSO) related weather conditions as they relate to the week
to-week changes in dengue incidence at a regional level. Materials and methods::
We collected data from 10 municipalities of the Olmeca region in Mexico, over a
10 year period (January 1995 to December 2005). Negative binomial models with
distributed lags were adjusted to look for associations between changes in the
weekly incidence rate of dengue fever and climate variability. Results:: Our
results show that it takes approximately six weeks for sea surface temperatures
(SST -34) to affect dengue incidence adjusted by weather and social variables.
Conclusion:: Such models could be used as early as two months in advance to
provide information to decision makers about potential epidemics. Elucidating the
effect of climatic variability and social variables, could assist in the
development of accurate early warning systems for epidemics like dengue,
Chikungunya and Zika.
PMID- 28423110
TI - ?
AB - Objective:: We aimed to explore organ donation and transplantation in Mexico from
the point of view of transplantation health professionals. Materials and
methods:: A qualitative study was carried out. Twenty six organ transplantation
health professionals from seven states of Mexico participated. Semi-structured
face-to-face interviews were conducted mainly in hospital settings. Critical
discourse analysis was performed. Results:: According to participants, living
organ transplantation offers benefits for recipients as well as for donors.
Several factors influence the field of transplantation negatively, among them the
scarcity of resources that impedes the incorporation of new health personnel, as
well as conflicts between transplantation teams with diverse health professionals
and authorities. Conclusion:: Besides increasing economic resources,
transplantation health personnel should be sensitized to find solutions in order
to avoid conflicts with different health professionals. Studies on organ donation
and transplants also should include other social actors' viewpoint.
PMID- 28423111
TI - [What is purchased, how and from whom by Seguro Popular in Mexico? Experience
with strategic purchasing at national level and in a pioneer institution].
AB - Objective:: To analyze the scope of demand subsidies through strategic purchasing
of health services. Materials and methods:: Interviews and document analyses at
national level and a case study of the state of Hidalgo. Results:: SPSS
explicitly prioritizes interventions to be financed and regulates prices and
expenditure ceilings. Public providers are predominantly funded through the
purchasing of inputs and the contracting of human resources, in the absence of
competition and with a low degree of managerial autonomy. Seguro Popular in
Hidalgo has diversified service providers and payment mechanisms. Conclusions::
SPSS has ample opportunity to extend and deepen strategic purchasing. Greater
decision-making autonomy of payers and providers is required, as well as
regulations to promote provider networks in competitive environments.
PMID- 28423112
TI - Prevalence trends of wood use as the main cooking fuel in Mexico, 1990-2013.
AB - Objective:: To determine prevalence trends of using Wood as the Main Cooking Fuel
(WMCF) in Mexico and household characteristics that predict its use. Materials
and methods:: Estimates were obtained from the 1990, 2000 and 2010 censuses and
from a national survey performed in 2012 and 2013. Results:: In 2012-2013, 9.5%
of the 66 321 surveyed households and 10.9% of their 252 011 residents used WMCF.
Prevalence was higher in rural (40.5%) than urban areas (1.5%), p<0.0001. From
1990 to 2013 wood use decreased by 53% overall and by 28.6% in rural areas, gas
use increased respectively by 17.5 and 52.7%. Predictors of using WMCF were
living in rural or suburban areas and those associated with low socioeconomic
status. Conclusion:: Use of WMCF has decreased substantially in Mexico but at a
slower pace in rural areas. Improving household characteristics and socioeconomic
status may decrease use of WMCF at a higher rate.
PMID- 28423113
TI - Time trends for tobacco and alcohol use in youth-rated films popular in Mexico
and Argentina, from 2004-2012.
AB - Objective:: To examine and compare overall prevalence and time trends in tobacco
and alcohol portrayals and brand appearances in youth-rated US and nationally
produced films that were the most successful in Argentina and Mexico from 2004
2012. Materials and methods:: Top-grossing nationally produced films from
Argentina (n=73), Mexico (n=85) and the US (n=643) were content analyzed.
Logistic regression was used to determine differences between Mexican, Argentine
and US produced films. Linear regression models assessed significant cross
country differences in the mean number of tobacco and alcohol seconds. Results::
Films from Mexico and Argentina were more likely than US films to contain
tobacco, (OR=4.2; p<0.001) and (OR=7.2; p<0.001). Alcohol was present in 93% of
Argentine, 83% in Mexican and 83% US films. Conclusions:: Smoking and alcohol
were highly prevalent in nationally produced films. They may have a significant
impact and should be targeted by policies to reduce youth exposure to portrayals
of risk behaviors.
PMID- 28423114
TI - Human papillomavirus vaccine efficacy in the prevention of anogenital warts:
systematic review and meta-analysis.
AB - Objective:: To review evidence on the efficacy of HPV vaccines in the prevention
of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis
and oral papillomatosis). Materials and methods:: We conducted a systematic
review of randomized trials. We performed random effect models and effects were
reported as relative risks (RR) and their confidence intervals (95%CI) following
both intention to treat (ITT) and per protocol (PP) analyses. Results:: We
included six studies (n=27 078). One study was rated as high risk of bias. One
study could not be included in the meta-analysis because it provided combined
results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR:
0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05,
95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in
women or with low-risk of bias provided similar results. Conclusion:: HPV
quadrivalent vaccine is efficacious in preventing AGW in men and women.
PMID- 28423115
TI - Analysis of cigarette demand in Argentina: the impact of price changes on
consumption and government revenues.
AB - Objective:: To estimate cigarette demand and to simulate a tax policy targeted to
reduce tobacco consumption. Materials and methods:: Demand was estimated using a
vector error correction model. Simulation exercises present the impact of a tax
increase on consumption and revenues. Results:: Changes in real income and the
real price of cigarettes affect the demand for cigarettes in Argentina. The long
term price elasticity is 0.279 (a 10% increase in real prices reduces cigarette
consumption by 2.79% per quarter) and the long term income elasticity is 0.411 (a
10% increase in real income raises consumption by 4.11% per quarter). Even in a
conservative scenario, simulations show that increasing the price of cigarettes
by 100% using excise taxes would maximize revenues and reduce cigarette
consumption. Conclusion:: There is sufficient room to increase taxes, reducing
cigarette consumption, while still increasing tax revenues.
PMID- 28423116
TI - [Experiences of street harassment and associations with perceptions of social
cohesion among women in Mexico City].
AB - Objective:: To document the frequency and forms of street harassment and examine
the association between street harassment experiences and perceptions of social
cohesion. Materials and methods:: Baseline survey data collected among women
seeking care in public health clinics in Mexico City were used for analysis.
Results:: Nearly two-thirds (62.8%) of women reported experiencing some form of
street harassment in the prior month; women with street harassment experiences
reported significantly lower perceived social cohesion (b=-0.46; 95%CI: -0.69,
0.22). Conclusions: : Findings indicate reducing street harassment may have
important implications for improving women's perceived social cohesion and their
safety in Mexico City.
PMID- 28423117
TI - [Recommendations for a multisectorial national policy to promote breastfeeding in
Mexico: position of the National Academy of Medicine].
AB - Evidence strongly supports that to improve breastfeeding practices it is needed
to strengthen actions of promotion, protection and support. To achieve this goal,
it is necessary to establish a multisectoral national policy that includes
elements such as design, implementation, monitoring and evaluation of programs
and policies, funding research, advocacy to develop political willingness, and
the promotion of breastfeeding from the national to municipal level, all
coordinated by a central level. It is until now that Mexico has initiated a
reform process to the establish a National Strategy for Breastfeeding Action.
This strategy, is the result not only of the consistent scientific evidence on
clear and strong benefits of breastfeeding on population health and the
development of human capital, but also for the alarming data of deterioration of
breastfeeding practices in the country. The comprehensive implementation of the
National Strategy for Breastfeeding Action that includes the establishment of a
national committee, intra- and inter-sectoral coordination of actions, setting
clear goals and monitoring the International Code of Marketing of Breast-Milk
Substitutes, is the awaiting responsibility of the public health agenda of the
country.
PMID- 28423118
TI - Obesity and kidney disease: hidden consequences of the epidemic.
AB - Obesity has become a worldwide epidemic and its prevalence has been projected to
grow by 40% in the next decade. This increasing prevalence has implications for
the risk of diabetes, cardiovascular disease and also for chronic kidney disease
(CKD). A high body mass index is one of the strongest risk factors for new-onset
CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to
meet the heightened metabolic demands of the increased body weight. The increase
in intraglomerular pressure can damage the kidneys and raise the risk of
developing CKD in the long-term. The incidence of obesity-related glomerulopathy
has increased ten-fold in recent years. Obesity has also been shown to be a risk
factor for nephrolithiasis, and for a number of malignancies including kidney
cancer. This year, the World Kidney Day will promote education on the harmful
consequences of obesity and its association with kidney disease, advocating
healthy lifestyle and health policy measures that make preventive behaviors an
affordable option.
PMID- 28423119
TI - Importance of SERCA2a on early isolated diastolic dysfunction induced by
supravalvular aortic stenosis in rats.
AB - Cardiac remodeling is defined as changes in shape and function of the heart in
response to aggression (pressure overload). The sarcoplasmic reticulum calcium
ATPase cardiac isoform 2a (SERCA2a) is a known factor that influences function. A
wide spectrum of studies report a decrease in SERCA2a in heart failure, but none
evaluate it's the role in early isolated diastolic dysfunction in supravalvular
aortic stenosis (AoS). Our hypothesis was that SERCA2a participates in such
dysfunction. Thirty-day-old male Wistar rats (60-80 g) were divided into AoS and
Sham groups, which were submitted to surgery with or without aorta clipping,
respectively. After 6 weeks, the animals were submitted to echocardiogram and
functional analysis by isolated papillary muscle (IPM) in basal condition,
hypoxia, and SERCA2a blockage with cyclopiazonic acid at calcium concentrations
of 0.5, 1.5, and 2.5 mM. Western-blot analyses were used for SERCA2a and
phospholamban detection. Data analysis was carried out with Student's t-test and
ANOVA. AoS enhanced left atrium and E and A wave ratio, with preserved ejection
fraction. Basal condition in IPM showed similar increases in developed tension
(DT) and resting tension (RT) in AoS, and hypoxia was similar between groups.
After cyclopiazonic acid blockage, final DT was equally decreased and RT was
similar between groups, but the speed of relaxation was decreased in the AoS
group. Western-blot was uniform in all evaluations. The hypothesis was confirmed,
since functional parameters regarding SERCA2a were changed in the AoS group.
PMID- 28423120
TI - Primary cultures of mouse small intestinal epithelial cells using the
dissociating enzyme type I collagenase and hyaluronidase.
AB - The epithelium is a highly dynamic system, which plays a crucial role in the
homeostasis of the intestinal tract. However, studies on the physiological and
pathophysiological functions of intestinal epithelial cells (IECs) have been
hampered due to lack of normal epithelial cell models. In the present study, we
established a reproducible method for primary culture of mouse IECs, which were
isolated from the viable small intestinal crypts of murine fetuses (on embryonic
day 19), using type I collagenase and hyaluronidase in a short span of time (<=20
min). With this method, continuously growing mouse IECs, which can be subcultured
over a number of passages, were obtained. The obtained cell lines formed a tight
cobblestone-like arrangement, displayed long and slender microvilli, expressed
characteristic markers (cytokeratin 18 and Notch-1), and generated increasing
transepithelial electrical resistance and low paracellular permeability during in
vitro culture. The cells also had enzymatic activities of alkaline phosphatase
and sucrase-isomaltase, and secreted various cytokines (IL-1beta, IL-6, IL-8, and
monocyte chemoattractant protein-1), responding to the stimulation of Escherichia
coli. These results show that the primary-cultured mouse IECs obtained by the
method established here had the morphological and immunological characteristics
of IECs. This culture system can be a beneficial in vitro model for studies on
mucosal immunology and toxicology.
PMID- 28423121
TI - Telomere length analysis in monoclonal B-cell lymphocytosis and chronic
lymphocytic leukemia Binet A.
AB - Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic clinical entity
characterized by the proliferation of monoclonal B cells not meeting the
diagnosis criteria for chronic lymphocytic leukemia (CLL). MBL may precede the
development of CLL, but the molecular mechanisms responsible for disease
progression and evolution are not completely known. Telomeres are usually short
in CLL and their attrition may contribute to disease evolution. Here, we
determined the telomere lengths of CD5+CD19+ cells in MBL, CLL, and healthy
volunteers. Twenty-one CLL patients, 11 subjects with high-count MBL, and 6 with
low-count MBL were enrolled. Two hundred and sixty-one healthy volunteers aged 0
to 88 years were studied as controls. After diagnosis confirmation, a flow
cytometry CD19+CD5+-based cell sorting was performed for the study groups.
Telomere length was determined by qPCR. Telomere length was similar in the 3
study groups but shorter in these groups compared to normal age-matched subjects
that had been enrolled in a previous study from our group. These findings suggest
that telomere shortening is an early event in CLL leukemogenesis.
PMID- 28423122
TI - Development and Validation of a Stratification Tool for Predicting Risk of Deep
Sternal Wound Infection after Coronary Artery Bypass Grafting at a Brazilian
Hospital.
AB - Objective: Deep sternal wound infection following coronary artery bypass grafting
is a serious complication associated with significant morbidity and mortality.
Despite the substantial impact of deep sternal wound infection, there is a lack
of specific risk stratification tools to predict this complication after coronary
artery bypass grafting. This study was undertaken to develop a specific
prognostic scoring system for the development of deep sternal wound infection
that could risk-stratify patients undergoing coronary artery bypass grafting and
be applied right after the surgical procedure. Methods: Between March 2007 and
August 2016, continuous, prospective surveillance data on deep sternal wound
infection and a set of 27 variables of 1500 patients were collected. Using binary
logistic regression analysis, we identified independent predictors of deep
sternal wound infection. Initially we developed a predictive model in a subset of
500 patients. Dataset was expanded to other 1000 consecutive cases and a final
model and risk score were derived. Calibration of the scores was performed using
the Hosmer-Lemeshow test. Results: The model had area under Receiver Operating
Characteristic (ROC) curve of 0.729 (0.821 for preliminary dataset). Baseline
risk score incorporated independent predictors of deep sternal wound infection:
obesity (P=0.046; OR 2.58; 95% CI 1.11-6.68), diabetes (P=0.046; OR 2.61; 95% CI
1.12-6.63), smoking (P=0.008; OR 2.10; 95% CI 1.12-4.67), pedicled internal
thoracic artery (P=0.012; OR 5.11; 95% CI 1.42-18.40), and on-pump coronary
artery bypass grafting (P=0.042; OR 2.20; 95% CI 1.13-5.81). A risk
stratification system was, then, developed. Conclusion: This tool effectively
predicts deep sternal wound infection risk at our center and may help with risk
stratification in relation to public reporting and targeted prevention strategies
in patients undergoing coronary artery bypass grafting.
PMID- 28423124
TI - The Importance of Peer-Reviewers. How to Recognize their Merits?
PMID- 28423123
TI - N-acetylcysteine versus Dopamine to Prevent Acute Kidney Injury after Cardiac
Surgery in Patients with Preexisting Moderate Renal Insufficiency.
AB - Objective: Acute kidney injury after cardiac surgery is associated with mortality
and morbidity. Therefore, strategies to prevent acute kidney injury are very
important. The aim of this placebo-controlled randomized double-blind study was
to compare the prophylactic efficacy of N-Acetylcysteine and dopamine
administration in patients with pre-existing moderate renal insufficiency who
were undergoing cardiopulmonary bypass. Methods: This study included 135 patients
with pre-existing moderate renal insufficiency who were scheduled for coronary
artery bypass grafting surgery. Serum creatinine and GFR were recorded
preoperatively and on the first and second postoperative days. Results: On the
first and second postoperative days, the drugs used showed statistically
significant differences among the creatinine groups (P<0.001). According to
Tukey's HSD, on the first and second PO, the creatinine of Group N, D and P were
significantly different (P<0.001). On the first and second PO, the used drugs
showed statistically significant differences among the effects of eGFR (P<0.001).
According to Tukey's HSD on the first postoperative day, the average eGFR score
of Group N compared to D and P were significantly difference (P<0.001). On the
second postoperative day, the eGFR of Group N and D showed no difference
(P=0.37), but P showed a difference (P<0.001). Conclusion: We found that the
prophylactic use of intravenous N-Acetylcysteine had a protective effect on renal
function, whereas the application of renal dose dopamine did not have a
protective effect in patients with pre-existing moderate renal failure.
PMID- 28423126
TI - Chronic Atrial Fibrillation Ablation with Harmonic Scalpel during Mitral Valve
Surgery.
AB - Objective: To evaluate surgical treatment of chronic atrial fibrillation with
ultrasound in patients with mitral valve disease, considering preoperative
clinical characteristics of patients undergoing surgical procedure and follow-up
in the immediate postoperative period, in hospital and up to 60 months after
discharge. Methods: We studied 100 patients with chronic atrial fibrillation and
mitral valve disease who underwent surgical treatment using ultrasound ablation.
Patient data were reviewed by consulting the control reports, including signs and
symptoms, underlying disease, functional class, hospital stay, surgical procedure
time, ablation time, immediate complications, and complications at discharged and
up to 60 months later. Actuarial curve (Kaplan-Meier) was used for the study of
permanence without recurrence after 12, 24, 36, 48 and 60 months. Results: 86% of
the patients had rheumatic mitral valve disease, 14% had degeneration of the
mitral valve, 40% had mitral regurgitation, and 36% had mitral stenosis. Main
symptoms included palpitations related to tachycardia by chronic atrial
fibrillation (70%), congestive heart failure (70%), and previous episodes of
acute pulmonary edema (27%). Early results showed that 94% of the patients
undergoing ultrasound ablation reversed the rate of chronic atrial fibrillation,
86% being in sinus rhythm and 8% in atrioventricular block. At hospital
discharge, maintenance of sinus rhythm was observed in 86% of patients and there
was recurrence of chronic atrial fibrillation in 8% of patients. At follow-up
after 60 months, 83.8% of patients maintained the sinus rhythm. Conclusion:
Surgical treatment of chronic atrial fibrillation with ultrasound concomitant
with mitral valve surgery is feasible and satisfactory, with maintenance of sinus
rhythm in most patients (83.8%) after 60 months of follow-up.
PMID- 28423125
TI - Coronary Arteriovenous Fistulas in Adult Patients: Surgical Management and
Outcomes.
AB - Objective: The aim of this study was to describe the demographic, clinical and
anatomic characteristics of coronary arteriovenous fistulas in adult patients who
underwent open cardiac surgery and to review surgical management and outcomes.
Methods: Twenty-one adult patients (12 female, 9 male; mean age: 56.1+/-7.9
years) who underwent surgical treatment for coronary arteriovenous fistulas were
retrospectively included in this study. Coronary angiography, chest X-ray,
electrocardiography and transthoracic echocardiography were preoperatively
performed in all patients. Demographic and clinical data were also collected.
Postoperative courses of all patients were monitored and postoperative
complications were noted. Results: A total of 25 coronary arteriovenous fistulas
were detected in 21 patients; the fistulas originated mainly from left anterior
descending artery (n=9, 42.8%). Four (19.4%) patients had bilateral fistulas
originating from both left anterior descending and right coronary artery. The
main drainage site of coronary arteriovenous fistulas was the pulmonary artery
(n=18, 85.7%). Twelve (57.1%) patients had isolated coronary arteriovenous
fistulas and 4 (19.4%), concomitant coronary artery disease. Twenty (95.3%) of
all patients were symptomatic. Seventeen patients were operated on with and 4
without cardiopulmonary bypass. There was no mortality. Three patients had
postoperative atrial fibrillation. One patient had pericardial effusion causing
cardiac tamponade who underwent reoperation. Conclusion: The decision of surgical
management should be made on the size and the anatomical location of coronary
arteriovenous fistulas and concomitant cardiac comorbidities. Surgical closure
with ligation of coronary arteriovenous fistulas can be performed easily with on
pump or off-pump coronary artery bypass grafting, even in asymptomatic patients
to prevent fistula related complications with very low risk of mortality and
morbidity.
PMID- 28423127
TI - Evaluation of Anomalous Coronary Arteries from the Pulmonary Artery.
AB - Objective: This study evaluated clinical and diagnostic findings, treatment
methods, and follow-up of cases of anomalous coronary arteries from the pulmonary
artery. Methods: The study included all cases diagnosed with anomalous coronary
arteries from the pulmonary artery between January 2012 and January 2016. Data
from patients' demographic characteristics, electrocardiography,
echocardiography, angiographic findings, operation, intensive care unit stay, and
follow-up were evaluated. Results: The study included 12 patients (8 male, 4
female), 10 with anomalous left coronary artery from the pulmonary artery
(ALCAPA) and 2 with anomalous right coronary artery from the pulmonary artery
(ARCAPA). Median age at diagnosis was 4 months (range, 1 month - 10 years old)
and median weight was 5.5 kg (range, 3-30 kg). The most common complaints were
murmur (n=7) and respiratory distress (n=5). In 4 cases, the initial diagnosis
was dilated cardiomyopathy. Electrocardiographs were pathologic in all cases.
Echocardiographic examination revealed medium to severe mitral valve
regurgitation in 4 cases and reduced (< 40%) ejection fraction in 6 patients. Of
the 12 patients, 8 underwent direct implantation of the left coronary artery into
the aorta, 2 underwent implantation of the right coronary artery into the aorta,
and the remaining 2 underwent a Takeuchi procedure. There were no early
mortalities. Median hospital stay was 20 days (range, 5-35 days). Median follow
up duration was 18 months (range, 5-36 months), and no cases required further
surgery during follow-up. Conclusions: Anomalous coronary arteries from the
pulmonary artery can be successfully repaired providing there is early diagnosis
and effective, appropriate intensive care unit follow-up. Therefore, coronary
artery origins should be evaluated carefully, especially in cases with dilated
cardiomyopathies.
PMID- 28423128
TI - Peratrial Device Closure of Atrial Septal Defect Under Transesophageal
Echocardiographic Guidance without Fluoroscopy Compared to Conventional On-Pump
Surgical Closure.
AB - Objective: This study is designed to evaluate the advantages between peratrial
device closure under transesophageal echocardiographic guidance and open heart
surgery in atrial septal defect. Methods: From November 2011 to September 2014,
28 patients with atrial septal defect were treated. Fourteen patients received
peratrial device closure under transesophageal echocardiographic guidance (TEE
group) and 14 patients received cardiopulmonary bypass (CPB group). Clinical
parameters during intraoperative and postoperative periods were examined.
Results: All patients recovered after surgery without serious complications.
Compared with that in CPB group, clinical observations in TEE group showed
significant decreases in the operation time (193.6+/-35.5 vs. 77.4+/-22.7 min,
P<0.05), periods in intensive care unit (31.6+/-23.3 vs. 17.5+/-8.1 hours,
P<0.05), fluid volume after operation (502.5+/-439.3 vs. 32.5+/-7.3 ml, P<0.05),
postoperative length of hospital stay (8.9+/-2.8 vs. 6.8+/-2.4 days, P<0.05) and
total hospitalization cost (7205.9+/-1617.6 vs. 5882.3+/-441.2 $, P<0.05).
Conclusion: The peratrial device closure of atrial septal defect under
transesophageal echocardiographic guidance is a mini-invasive, simple, safe and
effective intervention. Its use in the clinical practice should be encouraged.
PMID- 28423129
TI - Totally Percutaneous Access Using Perclose Proglide for Endovascular Treatment of
Aortic Diseases.
AB - Objective: To evaluate our experience following the introduction of a
percutaneous program for endovascular treatment of aortic diseases using Perclose
Proglide(r) assessing efficacy, complications and identification of potential
risk factors that could predict failure or major access site complications.
Methods: A retrospective cohort study during a two-year period was performed. All
the patients submitted to totally percutaneous endovascular repair (PEVAR) of
aortic diseases and transcatheter aortic valve implantation since we started the
total percutaneous approach with the preclosure technique from November 2013 to
December 2015 were included in the study. The primary endpoint was major
ipsilateral access complication, defined according to PEVAR trial. Results: In a
cohort of 123 patients, immediate technical success was obtained in 121 (98.37%)
patients, with only two (0.82%) cases in 242 vascular access sites that required
intervention immediately after the procedure. Pairwise comparisons revealed
increased major access complication among patients with >50% common femoral
artery (CFA) calcification vs. none (P=0.004) and > 50% CFA calcification vs. <
50% CFA calcification (P=0.002). Small artery diameter (<6.5 mm) also increased
major access complication compared to bigger diameters (> 6.5 mm) (P=0.027).
Conclusion: The preclosure technique with two Perclose Proglide(r) for PEVAR is
safe and effective. Complications occur more often in patients with unfavorable
access site anatomy and the success rate can be improved with proper patient
selection.
PMID- 28423130
TI - Bovine Pericardial Patch Augmentation of One Insufficient Aortic Valve Cusp with
Twenty-three-year Positive Clinical Follow-up Independent of the Patch
Degeneration.
AB - Scientific progress shall ultimately boost the current acceptance level for
conservative aortic valve surgery. The present text aimed to report the 23-year
long-term follow-up of one patient operated with bovine pericardium cusp
extension. Growing confidence in the efficacy of the operation will allow a more
expeditious indication for surgical treatment, as is already the case in mitral
valve repair. This change of attitude will certainly make it possible for
patients to be sent for operation in mild aortic valve regurgitation. The present
report reinforces the concept and highlights the impression that the aortic
valvoplasty, independent of the progressive bovine pericardium degeneration, may
positively change the natural history of the aortic valve insufficiency.
PMID- 28423131
TI - Thoracoabdominal Aortic Aneurysm in a HIV-positive Patient.
AB - Advent of antiretroviral therapy has increased survival of patients with human
immunodeficiency virus (HIV) infections, with the result that some of these
patients now develop degenerative diseases, such as atherosclerotic aneurysms.
Degenerative thoracoabdominal aortic aneurysm is rare in HIV patients. In this
report, a 63-year-old male patient with HIV submitted to open repair of
thoracoabdominal aortic aneurysm. The patient did not suffer any type of
complication in the perioperative period and remained well in a 28-month follow
up period. In summary, open repair still remains a good alternative for aortic
complex aneurysms even in HIV patients.
PMID- 28423132
TI - Repair of Penetrating Pericardial and Diaphragmatic Injury with Cormatrix(r)
Patch in a Case of Suicide Attempt.
AB - The authors report the case of a suicide attempt. A 59-year-old man with self
inflicted penetrating chest trauma underwent emergency cardiothoracic surgery.
Pre-operative computed tomography scan showed critical proximity between the
blade and the right ventricle. Intraoperative findings showed a pericardial
laceration and a huge diaphragmatic lesion with heart and abdominal organs
integrity. The diaphragm muscle was repaired with a CorMatrix(r) patch, an
acceptable alternative to the traditional synthetic mesh avoiding infection and
repeated herniation.
PMID- 28423133
TI - The Importance of the Proper Definition of Adulthood: What is and What is Not
Included in a Scientific Publication.
PMID- 28423134
TI - Infant mortality by color or race from Rondonia, Brazilian Amazon.
AB - OBJECTIVE: To analyze the quality of records for live births and infant deaths
and to estimate the infant mortality rate for skin color or race, in order to
explore possible racial inequalities in health. METHODS: Descriptive study that
analyzed the quality of records of the Live Births Information System and
Mortality Information System in Rondonia, Brazilian Amazonian, between 2006-2009.
The infant mortality rates were estimated for skin color or race with the direct
method and corrected by: (1) proportional distribution of deaths with missing
data related to skin color or race; and (2) application of correction factors. We
also calculated proportional mortality by causes and age groups. RESULTS: The
capture of live births and deaths improved in relation to 2006-2007, which
required lower correction factors to estimate infant mortality rate. The risk of
death of indigenous infant (31.3/1,000 live births) was higher than that noted
for the other skin color or race groups, exceeding by 60% the infant mortality
rate in Rondonia (19.9/1,000 live births). Black children had the highest
neonatal infant mortality rate, while the indigenous had the highest post
neonatal infant mortality rate. Among the indigenous deaths, 15.2% were due to
ill-defined causes, while the other groups did not exceed 5.4%. The proportional
infant mortality due to infectious and parasitic diseases was higher among
indigenous children (12.1%), while among black children it occurred due to
external causes (8.7%). CONCLUSIONS: Expressive inequalities in infant mortality
were noted between skin color or race categories, more unfavorable for indigenous
infants. Correction factors proposed in the literature lack to consider
differences in underreporting of deaths for skin color or race. The specific
correction among the color or race categories would likely result in exacerbation
of the observed inequalities. OBJETIVO: Analisar a qualidade dos registros de
nascidos vivos e de obitos infantis e estimar a taxa de mortalidade infantil
segundo cor ou raca, a fim de explorar iniquidades etnico-raciais em saude.
METODOS: Estudo descritivo que analisou a qualidade dos registros do Sistema de
Informacoes sobre Nascidos Vivos e do Sistema de Informacoes sobre Mortalidade em
Rondonia, Amazonia brasileira, entre 2006-2009. As taxas de mortalidade infantil
foram estimadas nas categorias de cor ou raca, pelo metodo direto, e corrigidas
por: (1) distribuicao proporcional dos obitos com cor ou raca ignorada; e (2)
aplicacao de fatores de correcao. Efetuou-se tambem o calculo da mortalidade
proporcional por causas e grupos etarios. RESULTADOS: Entre 2008-2009, a captacao
de nascimentos e obitos melhorou em relacao aos anos de 2006-2007, requerendo
fatores de correcao menores para estimar a taxa de mortalidade infantil. O risco
de morte de criancas indigenas (31,3/1.000 nascidos vivos) foi maior que o
registrado nos demais grupos de cor ou raca, excedendo em 60% a mortalidade
infantil media no estado (19,9/1.000 nascidos vivos). As criancas pretas
apresentaram as maiores taxas de mortalidade infantil neonatal, enquanto as
indigenas apresentaram as maiores taxas de mortalidade infantil pos-neonatal.
Observou-se que 15,2% dos obitos indigenas foram por causas mal definidas,
enquanto nos demais grupos nao ultrapassaram 5,4%. A mortalidade infantil
proporcional por doencas infecciosas e parasitarias foi maior entre indigenas, ao
passo que entre criancas pretas, sobressairam as causas externas (8,7%).
CONCLUSOES: Observaram-se expressivas iniquidades na mortalidade infantil entre
as categorias de cor ou raca, com situacao mais desfavoravel as criancas
indigenas. Os fatores de correcao propostos na literatura nao consideram
diferencas na subenumeracao de obitos entre as categorias de cor ou raca. A
correcao especifica entre as categorias de cor ou raca provavelmente resultaria
em exacerbacao das iniquidades observadas.
PMID- 28423135
TI - Childhood cancer and environmental integrity: a commentary and a proposal.
AB - Improvements in the health standards of developed and developing societies depend
primarily on the relationships between economy and environment. Recent long-term
changes in the chemical composition of man-made environments may be linked to
changes in the biology of human beings. Here we argue that children are at the
greatest risk of being affected by the dangerous effects of these changes, with
particular reference to cancer. The concept of cancer risk must be extended to
new contexts. Considering the increasing rates of chemical pollution and its
spreading in the environment, we illustrate a proposal aiming to protect the
human health, in an intra- and intergenerational perspective. A surveillance
system of occupational and residential exposures should be implemented to prevent
cancer risk in embryos and children.
PMID- 28423136
TI - Violence against women, Espirito Santo, Brazil.
AB - OBJECTIVE: To estimate the prevalence and factors associated with psychological,
physical and sexual violence in women victims of intimate partner violence
assisted in the primary care services. METHODS: This is a cross-sectional study,
conducted in 26 health units in Vitoria, State of Espirito Santo, from March to
September 2014. We interviewed 991 women aged 20-59 years. To classify the
psychological, physical and sexual violence, the World Health Organization
instrument on violence against women was used and a questionnaire to investigate
the sociodemographic, behavioral characteristics, and the women's family and life
history was developed. The statistical analyzes used were Poisson regression,
Fisher's exact test and Chi-square. RESULTS: The prevalence we observed were
psychological 25.3% (95%CI 22.6-28.2); physical 9.9% (95%CI 8.1-11.9) and sexual
5.7% (95%CI 4.3-7.3). Psychological violence remained associated with education,
marital status, maternal history of intimate partner violence, sexual violence in
childhood and drug use, while physical assault was related to age, education,
marital status and maternal history of intimate partner violence. Sexual violence
occurred the most among women with low income, and victims of sexual violence in
childhood. CONCLUSIONS: Psychological, physical and sexual violence showed highly
frequency among women assisted by primary care services. Sociodemographic and
behavioral factors, personal experiences, and maternal violence influence the
phenomenon. OBJETIVO: Estimar a prevalencia e os fatores associados as violencias
psicologica, fisica e sexual nas mulheres vitimas de violencia perpetrada pelo
parceiro intimo atendidas nos servicos de atencao primaria. METODOS: Estudo
transversal, realizado em 26 unidades de saude do municipio de Vitoria, no
Espirito Santo, de marco a setembro de 2014. Foram entrevistadas 991 usuarias de
20 a 59 anos. Para classificar as violencias psicologica, fisica e sexual foi
utilizado o instrumento da Organizacao Mundial de Saude sobre violencia contra a
mulher e um questionario foi elaborado para investigar as caracteristicas
sociodemograficas, comportamentais e de historia familiar e de vida da mulher. As
analises estatisticas utilizadas foram: regressao de Poisson, teste exato de
Fisher e Qui-quadrado. RESULTADOS: As prevalencias observadas foram: psicologica
25,3% (IC95% 22,6-28,2); fisica 9,9% (IC95% 8,1-11,9) e sexual 5,7% (IC95% 4,3
7,3). A violencia psicologica manteve-se associada a escolaridade, situacao
conjugal, historico materno de violencia por parceiro intimo, violencia sexual na
infancia e ter feito uso de drogas, enquanto a agressao fisica esteve relacionada
a idade, escolaridade, situacao conjugal e a historia materna de violencia por
parceiro intimo. A violencia sexual foi mais frequente nas mulheres de menor
renda e que sofreram abuso sexual na infancia. CONCLUSOES: As violencias
psicologica, fisica e sexual apresentaram alta magnitude entre as mulheres
usuarias dos servicos de atencao primaria de saude. Fatores sociodemograficos,
comportamentais e experiencias pessoal e materna de violencia influenciam a
ocorrencia do fenomeno.
PMID- 28423137
TI - Psychometric properties of the Vulnerability to Abuse Screening Scale for
screening abuse of older adults.
AB - OBJECTIVE: Adapt and evaluate the psychometric properties of the Vulnerability to
Abuse Screening Scale to identify risk of domestic violence against older adults
in Brazil. METHODS: The instrument was adapted and validated in a sample of 151
older adults from a geriatric reference center in the municipality of Belo
Horizonte, State of Minas Gerais, in 2014. We collected sociodemographic,
clinical, and abuse-related information, and verified reliability by
reproducibility in a sample of 55 older people, who underwent re-testing of the
instrument seven days after the first application. Descriptive and comparative
analyses were performed for all variables, with a significance level of 5%. The
construct validity was analyzed by the principal components method with a
tetrachoric correlation matrix, the reliability of the scale by the weighted
Kappa (Kp) statistic, and the internal consistency by the Kuder-Richardson
estimator formula 20 (KR-20). RESULTS: The average age of the participants was
72.1 years (DP = 6.96; 95%CI 70.94-73.17), with a maximum of 92 years, and they
were predominantly female (76.2%; 95%CI 69.82-83.03). When analyzing the
relationship between the scores of the Vulnerability to Abuse Screening Scale,
categorized by presence (score > 3) or absence (score < 3) of vulnerability to
abuse, with clinical and health conditions, we found statistically significant
differences for self-perception of health (p = 0.002), depressive symptoms (p =
0.000), and presence of rheumatism (p = 0.003). There were no statistically
significant differences between sexes. The Vulnerability to Abuse Screening Scale
acceptably evaluated validity in the transcultural adaptation process,
demonstrating dimensionality coherent with the original proposal (four factors).
In the internal consistency analysis, the instrument presented good results (KR
20 = 0.69) and the reliability via reproducibility was considered excellent for
the global scale (Kp = 0.92). CONCLUSIONS: The Vulnerability to Abuse Screening
Scale proved to be a valid instrument with good psychometric capacity for
screening domestic abuse against older adults in Brazil. OBJETIVO: Adaptar e
avaliar as propriedades psicometricas da Escala Triagem de Vulnerabilidade ao
Abuso (Vulnerability to Abuse Screening Scale - VASS) para identificar risco de
violencia domestica contra idosos no Brasil. METODOS: O instrumento foi adaptado
e validado em uma amostra de 151 idosos de um centro de referencia do idoso, do
municipio de Belo Horizonte, MG, em 2014. Foram coletadas informacoes
sociodemograficas, clinicas e relacionadas a abusos. A confiabilidade via
reprodutibilidade foi verificada em uma amostra de 55 idosos, submetidos ao
reteste do instrumento sete dias apos a primeira aplicacao. Foram realizadas
analises descritivas e comparativas para todas as variaveis, com nivel de
significancia de 5%. A validade de construto foi analisada pelo metodo de
componentes principais com matriz de correlacao tetracorica, a confiabilidade da
escala pela estatistica Kappa ponderado (Kp) e a consistencia interna pelo
estimador Kuder-Richardson formula 20 (KR-20). RESULTADOS: A idade media dos
participantes foi 72,1 anos (DP = 6,96; IC95% 70,94-73,17), com maxima de 92
anos, e o sexo foi predominantemente feminino (76,2%; IC95% 69,82-83,03). Ao
analisar a relacao entre os escores da Escala Triagem de Vulnerabilidade ao
Abuso, categorizados em presenca (indice > 3) ou ausencia (indice < 3) de
vulnerabilidade para abuso, com condicoes clinicas e de saude, encontramos
diferencas estatisticamente significantes para autopercepcao de saude (p =
0,002), sintomas depressivos (p = 0,000) e presenca de reumatismo (p = 0,003). Em
relacao ao sexo, nao houve diferenca estatisticamente significante. A Escala
Triagem de Vulnerabilidade ao Abuso comportou-se de forma aceitavel na avaliacao
da validade no processo de adaptacao transcultural, demonstrando dimensionalidade
coerente com a proposta original (quatro fatores). Na analise da consistencia
interna, o instrumento apresentou bons resultados (KR-20 = 0,69) e a
confiabilidade via reprodutibilidade foi considerara excelente para a escala
global (Kp = 0,92). CONCLUSOES: A Escala Triagem de Vulnerabilidade ao Abuso
mostra-se como instrumento valido e com boas capacidades psicometricas para o
rastreio de abuso domestico contra idosos no contexto brasileiro.
PMID- 28423138
TI - Intimate partner violence and maternal educational practice.
AB - OBJECTIVE: The objective of this study is to analyze the association between
intimate partner violence against women and maternal educational practice
directed to children at the beginning of formal education. METHODS: This is a
cross-sectional study, carried out between 2013 and 2014, with 631 mother/child
pairs, registered in the Family Health Strategy of the Health District II of the
city of Recife, State of Pernambuco, Brazil. It integrates a prospective cohort
study designed to investigate the consequences of exposure to intimate partner
violence in relation to the child who was born between 2005 and 2006. The
maternal educational practice has been assessed by the Parent-Child Conflict
Tactics Scale and the intimate partner violence by a questionnaire adapted from
the Multi-Country Study on Women's Health and Domestic Violence of the World
Health Organization. Intimate partner violence referred to the last 12 months and
was defined by specific acts of psychological, physical, and sexual violence
inflicted to women by the partner. The crude and adjusted prevalence ratios were
estimated for the association studied, using log-binomial regression. RESULTS:
The prevalence of intimate partner violence was 24.4%, and violent maternal
educational practice was 93.8%. The use of non-violent discipline was mentioned
by 97.6% of the women, coexisting with violent strategies of discipline. Children
whose mothers reported intimate partner violence presented a higher chance of
suffering psychological aggression (PR = 2.2; 95%CI 1.0-4.7). CONCLUSIONS: The
violence suffered by the mother interferes in the parental education. The
findings show high prevalence of violent maternal educational practice, pointing
to the need for interventions that minimize the damage of violence in women and
children. OBJETIVO: Analisar a associacao entre a violencia pelo parceiro intimo
contra a mulher e a pratica educativa materna direcionada as criancas no inicio
da escolaridade formal. METODOS: Estudo transversal, realizado entre 2013 e 2014,
com 631 pares mae/crianca, cadastradas na Estrategia de Saude da Familia do
Distrito Sanitario II da cidade do Recife, Pernambuco. Integra o estudo de coorte
prospectivo delineado para investigar as consequencias da exposicao a violencia
pelo parceiro intimo para a crianca que nasceu da gestacao que ocorreu entre 2005
e 2006. A pratica educativa materna foi avaliada pela escala de conflitos Parent
Child Conflict Tactics Scale e a violencia pelo parceiro intimo por um
questionario adaptado do Estudo Multipaises sobre a Saude da Mulher e Violencia
Domestica da Organizacao Mundial da Saude. A violencia pelo parceiro intimo
referiu-se aos ultimos 12 meses e foi definida por atos concretos de violencia
psicologica, fisica e sexual infligidos a mulher pelo parceiro. Foram estimadas
as razoes de prevalencia brutas e ajustadas para a associacao estudada,
utilizando-se a regressao log-binominal. RESULTADOS: A prevalencia da violencia
pelo parceiro intimo foi de 24,4%, e da pratica educativa materna violenta de
93,8%. O uso de disciplina nao violenta foi referido por 97,6% das mulheres,
coexistindo com estrategias violentas de disciplinamento. As criancas cujas maes
relataram violencia pelo parceiro intimo apresentaram maior chance de sofrer
agressao psicologica (RP = 2,2; IC95% 1,0-4,7). CONCLUSOES: A violencia sofrida
pela mae interfere na educacao parental. Os achados demonstram alta prevalencia
de pratica educativa materna que perpassa pela violencia, o que aponta para a
necessidade de intervencoes que minimizem os prejuizos da violencia na mulher e
na crianca.
PMID- 28423139
TI - Trend of leprosy in individuals under the age of 15 in Mato Grosso (Brazil), 2001
2013.
AB - OBJECTIVE: To identify the historical trend of leprosy epidemiological indicators
in individuals under the age of 15 in the state of Mato Grosso. METHODS:
Descriptive study with trend analysis of leprosy indicators in individuals under
the age of fifteen registered in the Mato Grosso's System for Notifiable Diseases
between 2001 and 2013. We used the Prais-Winsten procedure for analyzing
generalized linear regression at a significance level of 5%. We considered as
increasing time series when the annual percent change was positive, decreasing
when negative and stationary when there was no significant difference between its
value and zero. RESULTS: We analyzed 2455 cases of leprosy and the average
detection rate in individuals under the age of fifteen was 22.7 per 100 thousand
inhabitants. The trend of the general coefficient of incidence was decreasing,
with an average annual rate of -5.5% (95%CI -7.5--3.5). Increasing trend was
observed with an increase of 6.7% (95%CI 2.7-10.8) in the proportion of
multibacillary cases, 9.4% (95%CI 4.4-14.7) of cases diagnosed with dimorphic
clinical form and 14% (95%CI 7.9-20.4) of cases with physical disability level 2
at the time of diagnosis. There was an increasing trend in the average proportion
of examined contacts, with a growth of 4.1% (95%CI 1.2-7.1) and average
proportion of healing was precarious (39.7%), with stationary trend. CONCLUSIONS:
The historical trend of leprosy cases in individuals under the age of fifteen
proved to be decreasing in the period, however the trends of epidemiological
indicators such as the proportion of multibacillary cases, physical disability
level 2 and healing, indicate late diagnosis with stay sources of transmission
and consequent worsening of the disease in the state of Mato Grosso. OBJETIVO:
Identificar a tendencia historica dos indicadores epidemiologicos de hanseniase
em menores de 15 anos no estado de Mato Grosso. METODOS: Estudo descritivo com
analise de tendencia dos indicadores de hanseniase em menores de 15 anos
registrados no Sistema Nacional de Agravos de Notificacao de Mato Grosso, no
periodo de 2001 a 2013. Utilizou-se o procedimento de Prais-Winsten para analise
de regressao linear generalizada, adotando-se nivel de significancia de 5%.
Consideraram-se como serie temporal crescente quando a annual percent change era
positiva, decrescente quando negativa e estacionaria quando nao havia diferenca
significante entre seu valor e o zero. RESULTADOS: Foram analisados 2.455 casos
de hanseniase e o coeficiente medio de incidencia em menores de 15 anos foi de
22,7/100 mil habitantes. A tendencia geral do coeficiente de incidencia foi
decrescente, com uma annual percent change de -5,5% (IC95% -7,5-3,5). Observou-se
tendencia de crescimento, com incremento de 6,7% (IC95% 2,7-10,8) na proporcao
dos casos multibacilares, de 9,4% (IC95% 4,4-14,7) nos casos com forma clinica
dimorfa e de 14% (IC95% 7,9-20,4) nos casos com incapacidade fisica grau 2 no
momento do diagnostico da doenca. Verificou-se crescimento na proporcao dos
contatos de casos novos examinados, com incremento de 4,1% (IC95% 1,2-7,1) e
media da proporcao de cura considerada precaria (39,7%) com tendencia
estacionaria. CONCLUSOES: A tendencia historica dos casos de hanseniase em
menores de 15 anos mostrou-se decrescente no periodo. Entretanto, as tendencias
dos indicadores epidemiologicos, como a proporcao de casos multibacilares, de
incapacidade fisica grau 2 e de cura, indicam o diagnostico tardio com
permanencia de fontes de transmissibilidade e consequente agravo da endemia no
estado de Mato Grosso.
PMID- 28423140
TI - Arboviruses emerging in Brazil: challenges for clinic and implications for public
health.
AB - Arboviruses have been emerging in different parts of the world due to genetic
changes in the virus, alteration of the host and vector population dynamics, or
because of anthropogenic environmental factors. These viruses' capacity for
adaptation is notable, as well as the likelihood of their emergence and
establishment in new geographic areas. In Brazilian epidemiologic scenario, the
most common arboviruses are DENV, CHIKV, and ZIKV, although others may spread in
the country. Little is yet known of the impact of viral co-circulation, which
would theoretically result in more intense viremia or other immunological
alterations that could trigger autoimmune diseases, such as Guillain-Barre
syndrome. The impact on morbidity and mortality intensifies as extensive
epidemics lead to a high number of affected individuals, severe cases, and
implications for health services, mainly due to the absence of treatment,
vaccines, and effective prevention and control measures. RESUMO Notifica-se a
emergencia de arboviroses em diferentes regioes do planeta em decorrencia de
mudancas geneticas no virus, alteracao da dinamica populacional de hospedeiros e
vetores ou por fatores ambientais de origem antropogenica. E notavel a capacidade
de adaptacao desses virus e a possibilidade de emergirem e se estabelecerem em
novas areas geograficas. No contexto epidemiologico brasileiro, os arbovirus de
maior circulacao sao DENV, CHIKV e ZIKV, embora existam outros com potencial de
disseminacao no Pais. O impacto da cocirculacao viral ainda e pouco conhecido, a
qual teoricamente resultaria em viremias mais intensas ou outras alteracoes
imunologicas que poderiam ser o gatilho para doencas autoimunes, como a sindrome
de Guillain-Barre. O impacto na morbidade e mortalidade se intensifica a medida
que extensas epidemias pressupoem grande numero de individuos acometidos, casos
graves e implicacoes sobre os servicos de saude, principalmente diante da
ausencia de tratamento, vacinas e medidas efetivas de prevencao e controle.
PMID- 28423142
TI - Performing Percutaneous Coronary Intervention Without On-Site Cardiac Surgery Is
Not a License for Percutaneous Coronary Intervention Instead of Coronary Artery
Bypass Grafting-Reply.
PMID- 28423141
TI - Intimate partner violence and incidence of common mental disorder.
AB - OBJECTIVE: To investigate the association of intimate partner violence against
women reported in the last 12 months and seven years with the incidence of common
mental disorders. METHODS: A prospective cohort study with 390 women from 18 to
49 years, registered in the Family Health Program of the city of Recife, State of
Pernambuco; from July 2013 to December 2014. The Self Reporting Questionnaire-20
(SRQ-20) assessed mental health. Intimate partner violence consists of concrete
acts of psychological, physical or sexual violence that the partner inflicts on
the woman. Poisson regression was used to estimate crude and adjusted relative
risks (RR) of the association between common mental disorders and intimate
partner violence. RESULTS: The incidence of common mental disorders was 44.6%
among women who reported intimate partner violence in the last 12 months and
43.4% among those who reported in the past seven years. Mental disorders remained
associated with psychological violence (RR = 3.0; 95%CI 1.9-4.7 and RR = 1.8;
95%CI 1.0-3.7 in the last 12 months, and seven years, respectively), even in the
absence of physical or sexual violence. When psychological violence were related
to physical or sexual violence, the risk of common mental disorders was even
higher, both in the last 12 months (RR = 3.1; 95%CI 2.1-4.7) and in the last
seven years (RR = 2.5; 95%CI 1.7-3.8). CONCLUSIONS: Intimate partner violence is
associated with the incidence of common mental disorders in women. The treatment
of the consequences of IPV and support for women in seeking protection for
themselves for public services is essential. OBJETIVO: Investigar a associacao da
violencia por parceiros intimos relatada contra as mulheres nos ultimos 12 meses
e ultimos sete anos com a incidencia dos transtornos mentais comuns. METODOS:
Estudo de coorte prospectivo com 390 mulheres de 18 a 49 anos, cadastradas no
Programa Saude da Familia da cidade do Recife, PE, entre julho de 2013 e dezembro
de 2014. A saude mental foi avaliada pelo Self Reporting Questionnaire-20 (SRQ
20). A violencia por parceiro intimo foi definida por atos concretos de violencia
psicologica, fisica ou sexual infligidos a mulher pelo parceiro. A regressao de
Poisson foi utilizada para estimar os riscos relativos (RR) brutos e ajustados da
associacao entre transtorno mental comum e violencia por parceiro intimo.
RESULTADOS: A incidencia dos transtornos mentais comuns foi de 44,6% entre as
mulheres que relataram violencia nos ultimos 12 meses e de 43,4% nas que
relataram violencia nos ultimos sete anos. Os transtornos mentais mantiveram-se
associados a violencia psicologica (RR = 3,0; IC95% 1,9-4,7 e RR = 1,8; IC95% 1,0
3,7 nos ultimos 12 meses, e sete anos, respectivamente), mesmo na ausencia de
violencia fisica ou sexual. Quando a violencia psicologica esteve combinada com
violencia fisica ou sexual, o risco dos transtornos mentais comuns foi ainda mais
elevado, tanto nos ultimos 12 meses (RR = 3,1; IC95% 2,1-4,7) quanto nos ultimos
sete anos (RR = 2,5; IC95% 1,7-3,8). CONCLUSOES: A violencia por parceiro intimo
esta associada a incidencia de transtornos mentais comuns nas mulheres. E
fundamental o tratamento das consequencias da VPI e o apoio as mulheres na busca
de protecao para si pelos servicos publicos.
PMID- 28423143
TI - Leveraging the Benefits of Systemic Therapy to Tailor Surgery.
PMID- 28423144
TI - Efficacy of Catheter Ablation for Nonparoxysmal Atrial Fibrillation.
AB - Clinical Question: Is catheter ablation better than antiarrhythmic drugs for the
prevention of nonparoxysmal atrial fibrillation? Bottom Line: Radiofrequency
catheter ablation was found to be superior to antiarrhythmic drugs in preventing
recurrences of nonparoxysmal atrial fibrillation and reducing hospital
admissions.
PMID- 28423146
TI - Recovery in Patients With Dilated Cardiomyopathy With Loss-of-Function Mutations
in the Titin Gene.
PMID- 28423145
TI - Brief Behavioral Therapy for Pediatric Anxiety and Depression in Primary Care: A
Randomized Clinical Trial.
AB - Importance: Anxiety and depression affect 30% of youth but are markedly
undertreated compared with other mental disorders, especially in Hispanic
populations. Objective: To examine whether a pediatrics-based behavioral
intervention targeting anxiety and depression improves clinical outcome compared
with referral to outpatient community mental health care. Design, Setting, and
Participants: This 2-center randomized clinical trial with masked outcome
assessment conducted between brief behavioral therapy (BBT) and assisted referral
to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics
in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6,
2010, through December 5, 2014. Youths who met DSM-IV criteria for full or
probable diagnoses of separation anxiety disorder, generalized anxiety disorder,
social phobia, major depression, dysthymic disorder, and/or minor depression;
lived with a consenting legal guardian for at least 6 months; and spoke English
were included in the study. Exclusions included receipt of alternate treatment
for anxiety or depression, presence of a suicidal plan, bipolar disorder,
psychosis, posttraumatic stress disorder, substance dependence, current abuse,
intellectual disability, or unstable serious physical illness. Interventions: The
BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy
delivered in pediatric clinics by master's-level clinicians. The ARC families
received personalized referrals to mental health care and check-in calls to
support accessing care from master's-level coordinators. Main Outcomes and
Measures: The primary outcome was clinically significant improvement on the
Clinical Global Impression-Improvement scale (score <=2). Secondary outcomes
included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale
Revised, and functioning. Results: A total of 185 patients were enrolled in the
study (mean [SD] age, 11.3 [2.6] years; 107 [57.8%] female; 144 [77.8%] white;
and 38 [20.7%] Hispanic). Youths in the BBT group (n = 95), compared with those
in the ARC group (n = 90), had significantly higher rates of clinical improvement
(56.8% vs 28.2%; chi21 = 13.09, P < .001; number needed to treat, 4), greater
reductions in symptoms (F2,146 = 5.72; P = .004; Cohen f = 0.28), and better
functioning (mean [SD], 68.5 [10.7] vs 61.9 [11.9]; t156 = 3.64; P < .001; Cohen
d = 0.58). Ethnicity moderated outcomes, with Hispanic youth having substantially
stronger response to BBT (76.5%) than ARC (7.1%) (chi21 = 14.90; P < .001; number
needed to treat, 2). Effects were robust across sites. Conclusions and Relevance:
A pediatric-based brief behavioral intervention for anxiety and depression is
associated with benefits superior to those of assisted referral to outpatient
mental health care. Effects were especially strong for Hispanic participants,
suggesting that the protocol may be a useful tool in addressing ethnic
disparities in care. Trial Registration: clinicaltrials.gov Identifier:
NCT01147614.
PMID- 28423148
TI - Increasing Resident Autonomy Without Compromising Patient Safety.
PMID- 28423147
TI - Adherence to High-Intensity Statins Following a Myocardial Infarction
Hospitalization Among Medicare Beneficiaries.
AB - Importance: High-intensity statins are recommended following myocardial
infarction. However, patients may not continue taking this medication with high
adherence. Objective: To estimate the proportion of patients filling high
intensity statin prescriptions following myocardial infarction who continue
taking this medication with high adherence and to analyze factors associated with
continuing a high-intensity statin with high adherence after myocardial
infarction. Design, Setting, and Participants: Retrospective cohort study of
Medicare patients following hospitalization for myocardial infarction. Medicare
beneficiaries aged 66 to 75 years (n = 29 932) and older than 75 years (n = 27
956) hospitalized for myocardial infarction between 2007 and 2012 who filled a
high-intensity statin prescription (atorvastatin, 40-80 mg, and rosuvastatin, 20
40 mg) within 30 days of discharge. Beneficiaries had Medicare fee-for-service
coverage including pharmacy benefits. Exposures: Sociodemographic, dual
Medicare/Medicaid coverage, comorbidities, not filling high-intensity statin
prescriptions before their myocardial infarction (ie, new users), and cardiac
rehabilitation and outpatient cardiologist visits after discharge. Main Outcomes
and Measures: High adherence to high-intensity statins at 6 months and 2 years
after discharge was defined by a proportion of days covered of at least 80%, down
titration was defined by switching to a low/moderate-intensity statin with a
proportion of days covered of at least 80%, and low adherence was defined by a
proportion of days covered less than 80% for any statin intensity without
discontinuation. Discontinuation was defined by not having a statin available to
take in the last 60 days of each follow-up period. Results: Approximately half of
the beneficiaries were women and fourth-fifths were white. At 6 months and 2
years after discharge among beneficiaries 66 to 75 years of age, 17 633 (58.9%)
and 10 308 (41.6%) were taking high-intensity statins with high adherence, 2605
(8.7%) and 3315 (13.4%) down-titrated, 5182 (17.3%) and 4727 (19.1%) had low
adherence, and 3705 (12.4%) and 4648 (18.8%) discontinued their statin,
respectively. The proportion taking high-intensity statins with high adherence
increased between 2007 and 2012. African American patients, Hispanic patients,
and new high-intensity statin users were less likely to take high-intensity
statins with high adherence, and those with dual Medicare/Medicaid coverage and
more cardiologist visits after discharge and who participated in cardiac
rehabilitation were more likely to take high-intensity statins with high
adherence. Results were similar among beneficiaries older than 75 years of age.
Conclusions and Relevance: Many patients filling high-intensity statins following
a myocardial infarction do not continue taking this medication with high
adherence for 2 years postdischarge. Interventions are needed to increase high
intensity statin use and adherence after myocardial infarction.
PMID- 28423149
TI - Transdiagnostic Behavioral Therapies in Pediatric Primary Care: Looking Ahead.
PMID- 28423150
TI - Typographical Errors and Missing Table Footnote.
PMID- 28423151
TI - Diversity in Dermatology-A Call for Action.
PMID- 28423152
TI - Multiple Facial Trichoepitheliomas and Vulval Cysts: Extending the Phenotypic
Spectrum in CYLD Cutaneous Syndrome.
PMID- 28423153
TI - Heterogeneity in Blood Pressure Transitions Over the Life Course: Age-Specific
Emergence of Racial/Ethnic and Sex Disparities in the United States.
AB - Importance: Many studies have assessed racial/ethnic and sex disparities in the
prevalence of elevated blood pressure (BP) from childhood to adulthood, yet few
have examined differences in age-specific transitions between categories of BP
over the life course in contemporary, multiracial/multiethnic populations.
Objective: To estimate age, racial/ethnic, and sex-specific annual net transition
probabilities between categories of BP using Markov modeling of cross-sectional
data from the National Health and Nutrition Examination Survey. Design, Setting,
and Participants: National probability sample (National Health and Nutrition
Examination Survey in 2007-2008, 2009-2010, and 2011-2012) of 17 747 African
American, white American, and Mexican American participants aged 8 to 80 years.
The data were analyzed from September 2014 to November 2015. Main Outcomes and
Measures: Age-specific American Heart Association-defined BP categories. Results:
Three National Health and Nutrition Examination Survey cross-sectional samples
were used to characterize the ages at which self-reported African American (n =
4973), white American (n = 8886), and Mexican American (n = 3888) populations
transitioned between ideal BP, prehypertension, and hypertension across the life
course. At age 8 years, disparities in the prevalence of ideal BP were observed,
with the prevalence being lower among boys (86.6%-88.8%) compared with girls
(93.0%-96.3%). From ages 8 to 30 years, annual net transition probabilities from
ideal to prehypertension among male individuals were more than 2 times the net
transition probabilities of their female counterparts. The largest net transition
probabilities for ages 8 to 30 years occurred in African American young men,
among whom a net 2.9% (95% CI, 2.3%-3.4%) of those with ideal BP transitioned to
prehypertension 1 year later. Mexican American young women aged 8 to 30 years
experienced the lowest ideal to prehypertension net transition probabilities
(0.6%; 95% CI, 0.3%-0.8%). After age 40 years, ideal to prehypertension net
transition probabilities stabilized or decreased (range, 3.0%-4.5%) for men,
whereas net transition probabilities for women increased rapidly (range, 2.6%
13.0%). Mexican American women exhibited the largest ideal to prehypertension net
transition probabilities after age 60 years. The largest prehypertension to
hypertension net transition probabilities occurred at young ages in boys of white
race/ethnicity and African Americans, approximately age 8 years and age 25 years,
respectively, while net transition probabilities for white women and Mexican
Americans increased over the life course. Conclusions and Relevance:
Heterogeneity in net transition probabilities from ideal BP emerge during
childhood, with associated rapid declines in ideal BP observed in boys and
African Americans, thus introducing disparities. Primordial prevention beginning
in childhood and into early adulthood is necessary to preempt the development of
prehypertension and hypertension, as well as associated racial/ethnic and sex
disparities.
PMID- 28423155
TI - The Role of Genetic Testing in Patients With Breast Cancer: A Review.
AB - Importance: In the United States from 2009 to 2013, the incidence of breast
cancer was the highest of any cancer and the death rate was second to that of
lung cancer. Approximately 5% to 10% of breast cancers are inheritable.
Observations: BRCA1 and BRCA2 germline mutations account for up to 30% of
inheritable breast cancers and are the most commonly assessed mutations in
patients presenting with early-onset breast cancer, triple-negative breast
cancer, bilateral breast cancer, and a family history of breast cancer. Less
common non-BRCA mutations have also been identified and contribute to hereditary
breast cancer syndromes. Although established in BRCA mutations, indications and
interpretations of genetic testing in non-BRCA mutations are not well defined.
Furthermore, costs associated with genetic testing are highly variable and
dependent on laboratory pricing, insurance coverage, and individual risk factors.
Conclusions and Relevance: Genetic testing is a powerful tool that allows for the
detection of BRCA and non-BRCA germline mutations in individuals with high risks
of breast cancer, which in turn aids in the individualization of treatment. Given
the magnitude of this disease, it is of great benefit for physicians, including
general surgeons, to understand the indications, interpretations, and costs
associated with genetic testing in patients with breast cancer. Cost is an
especially important part of the genetic testing process and point of discussion
with patients.
PMID- 28423154
TI - Association of Mental Disorders and Related Medication Use With Risk for Major
Osteoporotic Fractures.
AB - Importance: Osteoporotic fractures are a leading cause of disability, costs, and
mortality. FRAX is a tool used to assess fracture risk in the general population.
Mental disorders and medications to treat them have been reported to adversely
affect bone health, but, to date, they have not been systematically studied in
relation to osteoporotic fractures. Objective: To examine the association of
mental disorders and psychotropic medication use with osteoporotic fracture risk
in routine clinical practice. Design, Setting, and Participants: In this
population-based cohort study, bone mineral density and risk factors were used to
calculate FRAX scores using data from the Manitoba Bone Density Program database
of all women and men 40 years of age or older in Manitoba, Canada, referred for a
baseline dual-energy x-ray absorptiometry scan from January 1, 1996, to March 28,
2013. Population-based health services data were used to identify primary mental
disorders during the 3 prior years, psychotropic medication use during the prior
year, and incident fractures. Cox proportional hazards regression models
estimated the risk for incident fractures based on mental disorders and use of
psychotropic medications. Data analysis was conducted from November 25, 2013, to
October 15, 2016. Main Outcomes and Measures: Incident nontraumatic major
osteoporotic fractures (MOFs) and hip fractures. Results: Of the 68 730
individuals (62 275 women and 6455 men; mean age, 64.2 [11.2] years) in the
study, during 485 322 person-years (median, 6.7 years) of observation, 5750
(8.4%) sustained an incident MOF, 1579 (2.3%) sustained an incident hip fracture,
and 8998 (13.1%) died. In analyses adjusted for FRAX score, depression was
associated with MOF (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.27-1.51; P <
.05) and hip fracture (aHR, 1.43; 95% CI, 1.22-1.69; P < .05) before adjustment
for medication use, but these associations were not significant after adjustment
for medication use. In contrast, the use of selective serotonin reuptake
inhibitors (aHR for MOF, 1.43; 95% CI, 1.27-1.60; P < .05; aHR for hip fracture,
1.48; 95% CI, 1.18-1.85; P < .05), antipsychotics (aHR for MOF, 1.43; 95% CI,
1.15-1.77; P < .05; aHR for hip fracture, 2.14; 95% CI, 1.52-3.02; P < .05), and
benzodiazepines (aHR for MOF, 1.15; 95% CI, 1.04-1.26; P < .05; aHR for hip
fracture, 1.24; 95% CI, 1.05-1.47; P < .05) were each independently associated
with significantly increased risk for both MOF and hip fracture. FRAX
significantly underestimated the 10-year risk of MOF by 29% and of hip fracture
by 51% for those with depression. It also underestimated the 10-year risk of MOF
by 36% for use of selective serotonin reuptake inhibitors, by 63% for use of mood
stabilizers, by 60% for use of antipsychotics, and by 13% for use of
benzodiazepines. FRAX underestimated the 10-year risk of hip fracture by 57% for
use of selective serotonin reuptake inhibitors, by 98% for use of mood
stabilizers, by 171% for use of antipsychotics, and by 31% for use of
benzodiazepines. FRAX correctly estimated fracture risk in people without mental
disorders and those not taking psychotropic medications. Conclusions and
Relevance: Mental disorders and medication use were associated with an increased
risk for fracture, but in simultaneous analyses, only medication use was
independently associated with fracture. Depression and psychotropic medication
use are potential risk indicators that are independent of FRAX estimates.
PMID- 28423156
TI - Creation of an Internal Teledermatology Store-and-Forward System in an Existing
Electronic Health Record: A Pilot Study in a Safety-Net Public Health and
Hospital System.
AB - Importance: External store-and-forward (SAF) teledermatology systems operate
separately from the primary health record and have many limitations, including
care fragmentation, inadequate communication among clinicians, and privacy and
security concerns, among others. Development of internal SAF workflows within
existing electronic health records (EHRs) should be the standard for large health
care organizations for delivering high-quality dermatologic care, improving
access, and capturing other telemedicine benchmark data. Epic EHR software (Epic
Systems Corporation) is currently one of the most widely used EHR system in the
United States, and development of a successful SAF workflow within it is needed.
Objectives: To develop an SAF teledermatology workflow within the Epic system,
the existing EHR system of Parkland Health and Hospital System (Dallas, Texas),
assess its effectiveness in improving access to care, and validate its
reliability; and to evaluate the system's ability to capture meaningful outcomes.
Design, Setting, and Participants: Electronic consults were independently
evaluated by 2 board-certified dermatologists, who provided diagnoses and
treatment plans to primary care physicians (PCPs). Results were compared with in
person referrals from May to December 2013 from the same clinic (a community
outpatient clinic in a safety-net public hospital system). Patients were those 18
years or older with dermatologic complaints who would have otherwise been
referred to dermatology clinic. Main Outcomes and Measures: Median time to
evaluation; percentage of patients evaluated by a dermatologist through either
teledermatology or in-person compared with the previous year. Results: Seventy
nine teledermatology consults were placed by 6 PCPs from an outpatient clinic
between May and December 2014; 57 (74%) were female and their mean (SD) age was
47.0 (12.4) years. Teledermatology reduced median time to evaluation from 70.0
days (interquartile range [IQR], 33.25-83.0 days) to 0.5 days (IQR, 0.172-0.94
days) and median time to treatment from 73.5 to 3.0 days compared with in-person
dermatology visits. Overall, a greater percentage of patients (120 of 144
[83.3%]) were evaluated by a dermatologist through either teledermatology or in
person during the 2014 study period compared with the previous year (111 of 173
[64.2%]). Primary care physicians followed management recommendations 93% of the
time. Conclusions and Relevance: Epic-based SAF teledermatology can improve
access to dermatologic care in a public safety-net hospital setting. We hope that
the system will serve as a model for other health care organizations wanting to
create SAF teledermatology workflows within the Epic EHR system.
PMID- 28423157
TI - Hypertension Disparities: The Hidden Vulnerability of Youth.
PMID- 28423158
TI - Declining Melanoma Rates in New England States.
PMID- 28423159
TI - Performing Percutaneous Coronary Intervention Without On-site Cardiac Surgery Is
Not a License for Percutaneous Coronary Intervention Instead of Coronary Artery
Bypass Grafting.
PMID- 28423160
TI - Sex First-A New View of the Origins of Eukaryotes.
PMID- 28423161
TI - An Unusual Case of Syringocystadenocarcinoma Papilliferum In Situ With Macular
Amyloidosis.
PMID- 28423162
TI - A Pilot Use of Patient-Generated Wound Data to Improve Postdischarge Surgical
Site Infection Monitoring.
PMID- 28423163
TI - Metafrontier frameworks for studying hospital productivity growth and quality
changes.
AB - Objective: The objective of this study was to evaluate productivity growth and
quality changes among different levels of accredited hospitals. Design: This
study used an attribute-incorporating Malmquist productivity index (MPI) under
the metafrontier framework. This is the first attempt to compare productivity
changes among hospitals operating under different production frontiers.
Participants: The data consisted of 20 academic medical centers (AMCs), 61
metropolitan hospitals (MPs) and 112 local community hospitals (LCs) in Taiwan
during the period 2007-2010. Main outcome measures: This study measured
productivity growth and further identified technological gaps and catch-ups in
different groups of hospitals with respect to the metafrontier. At the same time,
comparisons of changes in quality among different levels of hospitals were also
examined. Results: We found that the sample hospitals of AMCs and MPs experienced
productivity improvements mainly due to technological progress, but their
efficiency and technology gap ratio (TGR) deteriorated. As for LCs, progress in
technology along with improvements in their efficiency and TGR led to the highest
productivity upgrade among the three groups of hospitals. We also found that the
sample hospitals among the three groups showed improvements in quality. Moreover,
hospitals in the local community group exhibited greater quality progress than
the AMCs and MPs over the sample period. Conclusion: This paper presents a number
of useful decompositions of the metafrontier MPI, which can provide useful
insights into changes that are due to efficiency, quality improvements and/or
technological changes in the healthcare sector.
PMID- 28423164
TI - Triple Aim in Canada: developing capacity to lead to better health, care and
cost.
AB - Quality problem: Many modern health systems strive for 'Triple Aim' (TA)-better
health for populations, improved experience of care for patients and lower costs
of the system, but note challenges in implementation. Outcomes of applying TA as
a quality improvement framework (QI) have started to be realized with early
lessons as to why some systems make progress while others do not. Initial
assessment: Limited evidence is available as to how organizations create the
capacity and infrastructure required to design, implement, evaluate and sustain
TA systems. Choice of solution: To support embedding TA across Canada, the
Canadian Foundation for Healthcare Improvement supported enrolment of nine
Canadian teams to participate in the Institute for Healthcare Improvement's TA
Improvement Community. Implementation: Structured support for TA design,
implementation, evaluation and sustainability was addressed in a collaborative
programme of webinars and action periods. Teams were coached to undertake and
test small-scale improvements before attempting to scale. Evaluation: A summative
evaluation of the Canadian cohort was undertaken to assess site progress in
building TA infrastructure across various healthcare settings. The evaluation
explored the process of change, experiences and challenges and strategies for
continuous QI. Lessons learned: Delivering TA requires a sustained and
coordinated effort supported by strong leadership and governance, continuous QI,
engaged interdisciplinary teams and partnering within and beyond the healthcare
sector.
PMID- 28423165
TI - A randomized comparison between league tables and funnel plots to inform health
care decision-making.
AB - Objective: Comparison of provider performance is commonly used to inform health
care decision-making. Little attention has been paid to how data presentations
influence decisions. This study analyzes differences in suggested actions by
decision-makers informed by league tables or funnel plots. Design: Decision
makers were invited to a survey and randomized to compare hospital performance
using either league tables or funnel plots for four different measures within the
area of cancer care. For each measure, decision-makers were asked to suggest
actions towards 12-16 hospitals (no action, ask for more information, intervene)
and provide feedback related to whether the information provided had been useful.
Setting: Swedish health care. Participants: Two hundred and twenty-one decision
makers at administrative and clinical levels. Intervention: Data presentations in
the form of league tables or funnel plots. Main outcome measures: Number of
actions suggested by participants. Proportion of appropriate actions. Results:
For all four measures, decision-makers tended to suggest more actions based on
the information provided in league tables compared to funnel plots (44% vs. 21%,
P < 0.001). Actions were on average more appropriate for funnel plots. However,
when using funnel plots, decision-makers more often missed to react even when
appropriate. Conclusions: The form of data presentation had an influence on
decision-making. With league tables, decision-makers tended to suggest more
actions compared to funnel plots. A difference in sensitivity and specificity
conditioned by the form of presentation could also be identified, with different
implications depending on the purpose of comparisons. Explanations and
visualization aids are needed to support appropriate actions.
PMID- 28423166
TI - Leonine Facies, Flushing, and Systemic Symptoms.
PMID- 28423167
TI - What pre-Columbian mummies could teach us about South American leishmaniases?
AB - A recent report on the taxonomic profile of the human gut microbiome in pre
Columbian mummies (Santiago-Rodriguez et al. 2016) gives for the first time
evidence of the presence of Leishmania DNA (sequences similar to Leishmania
donovani according to the authors) that can be reminiscent of visceral
leishmaniasis during the pre-Columbian era. It is commonly assumed that
Leishmania infantum, the etiological agent of American visceral leishmaniasis
(AVL) was introduced into the New World by the Iberian conquest. This finding is
really surprising and must be put into perspective with what is known from an AVL
epidemiological and historical point of view. Beside L. infantum, there are other
species that are occasionally reported to cause AVL in the New World. Among
these, L. colombiensis is present in the region of pre-Columbian mummies studied.
Other explanations for these findings include a more ancient introduction of a
visceral species of Leishmania from the Old World or the existence of a yet
unidentified endemic species causing visceral leishmaniasis in South America.
Unfortunately, very few molecular data are known about this very long pre
Columbian period concerning the circulating species of Leishmania and their
diversity in America.
PMID- 28423168
TI - The significance of Candida in the human respiratory tract: our evolving
understanding.
AB - Candida is an opportunistic pathogen and the most commonly isolated fungal genus
in humans. Though Candida is often detected in respiratory specimens from humans
with and without lung disease, its significance remains undetermined. While
historically considered a commensal organism with low virulence potential, the
status of Candida as an innocent bystander has recently been called into question
by both clinical observations and animal experimentation. We here review what is
currently known and yet to be determined about the clinical, microbiological and
pathophysiological significance of the detection of Candida spp. in the human
respiratory tract.
PMID- 28423169
TI - Innate immune response to lipooligosaccharide: pivotal regulator of the
pathobiology of invasive Neisseria meningitidis infections.
AB - Infections due to Neisseria meningitidis afflict more than one million people
worldwide annually and cause death or disability in many survivors. The clinical
course of invasive infections has been well studied, but our understanding of the
cause of differences in patient outcomes has been limited because these are
dependent on multiple factors including the response of the host, characteristics
of the bacteria and interactions between the host and the bacteria. The
meningococcus is a highly inflammatory organism, and the lipooligosaccharide
(LOS) on the outer membrane is the most potent inflammatory molecule it expresses
due to the interactions of the lipid A moiety of LOS with receptors of the innate
immune system. We previously reported that increased phosphorylation of
hexaacylated neisserial lipid A is correlated with greater inflammatory
potential. Here we postulate that variability in lipid A phosphorylation can tip
the balance of innate immune responses towards homeostatic tolerance or
proinflammatory signaling that affects adaptive immune responses, causing disease
with meningitis only, or septicemia with or without meningitis, respectively.
Furthermore, we propose that studies of the relationship between bacterial
virulence and gene expression should consider whether genetic variation could
affect properties of biosynthetic enzymes resulting in LOS structural differences
that alter disease pathobiology.
PMID- 28423170
TI - US Emergency Department Encounters for Law Enforcement-Associated Injury, 2006
2012.
PMID- 28423171
TI - Identification of Patients With Documented Pathologic Complete Response in the
Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery.
AB - Importance: A pathologic complete response (pCR; no invasive or in situ cancer)
occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative
(TN) breast cancer. The need for surgery if percutaneous biopsy of the breast
after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter
referred to as breast pCR) has been questioned, and appropriate management of the
axilla in such patients is unknown. Objective: To identify patients among
exceptional responders to NCT with a low risk for axillary metastases when breast
pCR is documented who may be eligible for an omission of surgery clinical trial
design. Design, Setting, and Participants: This prospective cohort study at a
single-institution academic national comprehensive cancer center included 527
consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT
followed by standard breast and nodal surgery from January 1, 2010, through
December 31, 2014. Main Outcomes and Measures: Patients who achieved a breast pCR
were compared with patients who did not based on subtype, initial
ultrasonographic findings, and documented pathologic nodal status. Incidence of
positive findings for nodal disease on final pathologic review was calculated for
patients with and without pCR and compared using relative risk ratios with 95%
CIs. Results: The analysis included 527 patients (median age, 51 [range, 23-84]
years). Among 290 patients with initial nodal ultrasonography showing N0 disease,
116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node
metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease,
69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence
of residual nodal disease (P < .01). Patients without a breast pCR had a relative
risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared
with those with a breast pCR. Conclusions and Relevance: Breast pCR is highly
correlated with nodal status after NCT, and the risk for missing nodal metastases
without axillary surgery in this cohort is extremely low. These data provide the
fundamental basis and rationale for management of the axilla in clinical trials
of omission of cancer surgery when image-guided biopsy indicates a breast pCR.
PMID- 28423174
TI - Comparison of Efficacy and Safety Between Propranolol and Steroid for Infantile
Hemangioma: A Randomized Clinical Trial.
AB - Importance: There are limited data from randomized clinical trials comparing
propranolol and steroid medication for treatment of infantile hemangioma (IH).
Objective: To determine the efficacy and safety of propranolol compared with
steroid as a first-line treatment for IH. Design, Setting, and Participants: This
randomized clinical noninferiority trial tested the efficacy and safety of
propranolol vs steroid treatment for IH at a single academic hospital. All
participants were diagnosed with IH between June 2013 and October 2014, had
normal heart function, and had not been previously treated for IH. Interventions:
The participants were randomly assigned to either the propranolol group or the
steroid group. In the propranolol group, the patients were admitted, observed for
adverse effects for 3 days after treatment initiation, and then released and
treated as outpatients for 16 weeks (2 mg/kg/d). In the steroid group, the
patients were seen as outpatients from the beginning and were also treated for 16
weeks (2 mg/kg/d). Main Outcomes and Measures: The primary efficacy variable was
the response to treatment at 16 weeks, which was evaluated by the hemangioma
volume using magnetic resonance imaging before and at 16 weeks after treatment
initiation. While comparing the effect of medication between the groups, we
monitored the adverse effects of both drugs. Results: A total of 34 patients (15
boys, 19 girls; mean age, 3.3 months; range, 0.3-8.2 months) were randomized to
receive either propranolol or steroid treatment (17 in each treatment group).
Guardians for 2 patients in the steroid group withdrew their consent, and 1
patient in the propranolol group did not complete the efficacy test. The
intention-to-treat analysis, applying multiple imputations, found the treatment
response rate in the propranolol group to be 95.65%, and that of the steroid
group was 91.94%. Because the difference in response rate between the groups was
3.71%, propranolol was considered noninferior. We found that there was no
difference between the groups in safety outcomes. Conclusions and Relevance: Our
trial demonstrated that propranolol was not inferior to steroid with respect to
therapeutic effects in IH. Trial Registration: clinicaltrials.gov Identifier:
NCT01908972.
PMID- 28423177
TI - Comparison of Appendectomy Outcomes Between Senior General Surgeons and General
Surgery Residents.
AB - Importance: In some centers, the presence of a senior general surgeon (SGS) is
obligatory in every procedure, including appendectomy, while in others it is not.
There is a relative paucity in the literature of reports comparing the outcomes
of appendectomies performed by unsupervised general surgery residents (GSRs) with
those performed in the presence of an SGS. Objective: To compare the outcomes of
appendectomies performed by SGSs with those performed by GSRs. Design, Setting,
and Participants: A retrospective analysis was performed of all patients 16 years
or older operated on for assumed acute appendicitis between January 1, 2008, and
December 31, 2015. The cohort study compared appendectomies performed by SGSs and
GSRs in the general surgical department of a teaching hospital. Main Outcomes and
Measures: The primary outcome measured was the postoperative early and late
complication rates. Secondary outcomes included time from emergency department to
operating room, length of surgery, surgical technique (open or laparoscopic), use
of laparoscopic staplers, and overall duration of postoperative antibiotic
treatment. Results: Among 1649 appendectomy procedures (mean [SD] patient age,
33.7 [13.3] years; 612 female [37.1%]), 1101 were performed by SGSs and 548 by
GSRs. Analysis demonstrated no significant difference between the SGS group and
the GSR group in overall postoperative early and late complication rates, the use
of imaging techniques, time from emergency department to operating room,
percentage of complicated appendicitis, postoperative length of hospital stay,
and overall duration of postoperative antibiotic treatment. However, length of
surgery was significantly shorter in the SGS group than in the GSR group (mean
[SD], 39.9 [20.9] vs 48.6 [20.2] minutes; P < .001). Conclusions and Relevance:
This study demonstrates that unsupervised surgical residents may safely perform
appendectomies, with no difference in postoperative early and late complication
rates compared with those performed in the presence of an SGS.
PMID- 28423179
TI - Glucan synthase-like 2 is indispensable for paramylon synthesis in Euglena
gracilis.
AB - The phytoflagellate Euglena gracilis produces a large amount of paramylon (PM), a
conglomerate of liner beta-1,3-glucan chains, as a storage polysaccharide. PM is
synthesized from uridine diphosphate-glucose, but its mechanism of formation is
largely unknown. Two enzymes, glucan synthase-like (EgGSL) 1 and EgGSL2 were
previously identified as candidates for PM synthesis in a Euglena transcriptome
analysis. Here, we performed a reverse genetic analysis on these enzymes.
Knockdown of EgGSL2, but not EgGSL1, significantly inhibits PM accumulation in
Euglena cells. Additionally, beta-1,3-glucan synthesis is detected in a PM
associated membrane fraction extracted from Euglena cells. Our findings indicate
that EgGSL2 is the predominant enzyme for PM biosynthesis.
PMID- 28423180
TI - MiR-19 regulates breast cancer cell aggressiveness by targeting profilin 1.
PMID- 28423178
TI - Head-to-head comparison of structurally unrelated dipeptidyl peptidase 4
inhibitors in the setting of renal ischemia reperfusion injury.
AB - BACKGROUND AND PURPOSE: Results regarding protective effects of dipeptidyl
peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are
conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a
model of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized
male rats by renal artery clamping for 30 min. The sham group was
uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given
p.o. once daily on three consecutive days prior to IRI: linagliptin (1.5 mg.kg-1
.day-1 ), vildagliptin (8 mg.kg-1 .day-1 ) and sitagliptin (30 mg.kg-1 .day-1 ).
An additional group received sitagliptin until study end (before IRI: 30 mg.kg-1
.day-1 ; after IRI: 15 mg.kg-1 .day-1 ). KEY RESULTS: Plasma-active glucagon-like
peptide type 1 (GLP-1) increased threefold to fourfold in all DPP4 inhibitor
groups 24 h after IRI. Plasma cystatin C, a marker of GFR, peaked 48 h after IRI.
Compared with the placebo group, DPP4 inhibition did not reduce increased plasma
cystatin C levels. DPP4 inhibitors ameliorated histopathologically assessed
tubular damage with varying degrees of drug-specific efficacies. Renal
osteopontin expression was uniformly reduced by all DPP4 inhibitors. IRI-related
increased renal cytokine expression was not decreased by DPP4 inhibition. Renal
DPP4 activity at study end was significantly inhibited in the linagliptin group,
but only numerically reduced in the prolonged/dose-adjusted sitagliptin group.
Active GLP-1 plasma levels at study end were increased only in the prolonged/dose
adjusted sitagliptin treatment group. CONCLUSIONS AND IMPLICATIONS: In rats with
renal IRI, DPP4 inhibition did not alter plasma cystatin C, a marker of
glomerular function, but may protect against tubular damage.
PMID- 28423181
TI - Mesenteric lymph node CD11b- CD103+ PD-L1High dendritic cells highly induce
regulatory T cells.
AB - Dendritic cells (DCs) in mesenteric lymph nodes (MLNs) induce Foxp3+ regulatory T
cells to regulate immune responses to beneficial or non-harmful agents in the
intestine, such as commensal bacteria and foods. Several studies in MLN DCs have
revealed that the CD103+ DC subset highly induces regulatory T cells, and another
study has reported that MLN DCs from programmed death ligand 1 (PD-L1) -deficient
mice could not induce regulatory T cells. Hence, the present study investigated
the expression of these molecules on MLN CD11c+ cells. Four distinct subsets
expressing CD103 and/or PD-L1 were identified, namely CD11b+ CD103+ PD-L1High ,
CD11b- CD103+ PD-L1High , CD11b- CD103+ PD-L1Low and CD11b+ CD103- PD-L1Int .
Among them, the CD11b- CD103+ PD-L1High DC subset highly induced Foxp3+ T cells.
This subset expressed Aldh1a2 and Itgb8 genes, which are involved in retinoic
acid metabolism and transforming growth factor-beta (TGF-beta) activation,
respectively. Exogenous TGF-beta supplementation equalized the level of Foxp3+ T
cell induction by the four subsets whereas retinoic acid did not, which suggests
that high ability to activate TGF-beta is determinant for the high Foxp3+ T-cell
induction by CD11b- CD103+ PD-L1High DC subset. Finally, this subset exhibited a
migratory DC phenotype and could take up and present orally administered
antigens. Collectively, the MLN CD11b- CD103+ PD-L1High DC subset probably takes
up luminal antigens in the intestine, migrates to MLNs, and highly induces
regulatory T cells through TGF-beta activation.
PMID- 28423183
TI - Long-term species loss and homogenization of moth communities in Central Europe.
AB - As global biodiversity continues to decline steeply, it is becoming increasingly
important to understand diversity patterns at local and regional scales. Changes
in land use and climate, nitrogen deposition and invasive species are the most
important threats to global biodiversity. Because land use changes tend to
benefit a few species but impede many, the expected outcome is generally
decreasing population sizes, decreasing species richness at local and regional
scales, and increasing similarity of species compositions across sites (biotic
homogenization). Homogenization can be also driven by invasive species or effects
of soil eutrophication propagating to higher trophic levels. In contrast, in the
absence of increasing aridity, climate warming is predicted to generally increase
abundances and species richness of poikilotherms at local and regional scales. We
tested these predictions with data from one of the few existing monitoring
programmes on biodiversity in the world dating to the 1960s, where the abundance
of 878 species of macro-moths have been measured daily at seven sites across
Hungary. Our analyses revealed a dramatic rate of regional species loss and
homogenization of community compositions across sites. Species with restricted
distribution range, specialized diet or dry grassland habitat were more likely
than others to disappear from the community. In global context, the contrasting
effects of climate change and land use changes could explain why the predicted
enriching effects from climate warming are not always realized.
PMID- 28423182
TI - Crystal structure of the EnvZ periplasmic domain with CHAPS.
AB - Bacteria sense and respond to osmolarity through the EnvZ-OmpR two-component
system. The structure of the periplasmic sensor domain of EnvZ (EnvZ-PD) is not
available yet. Here, we present the crystal structure of EnvZ-PD in the presence
of CHAPS detergent. The structure of EnvZ-PD shows similar folding topology to
the PDC domains of PhoQ, DcuS, and CitA, but distinct orientations of helices and
beta-hairpin structures. The CD and NMR spectra of EnvZ-PD in the presence of
cholate, a major component of bile salts, are similar to those with CHAPS.
Chemical cross-linking shows that the dimerization of EnvZ-PD is significantly
inhibited by the CHAPS and cholate. Together with beta-galactosidase assay, these
results suggest that bile salts may affect the EnvZ structure and function in
Escherichia coli.
PMID- 28423184
TI - The differentiated and conserved roles of Swi5-Sfr1 in homologous recombination.
AB - Homologous recombination (HR) is the process whereby two DNA molecules that share
high sequence similarity are able to recombine to generate hybrid DNA molecules.
Throughout evolution, the ability of HR to identify highly similar DNA sequences
has been adopted for numerous biological phenomena including DNA repair, meiosis,
telomere maintenance, ribosomal DNA amplification and immunological diversity.
Although Rad51 and Dmc1 are the key proteins that promote HR in mitotic and
meiotic cells, respectively, accessory proteins that allow Rad51 and Dmc1 to
effectively fulfil their functions have been identified in all examined model
systems. In this Review, we discuss the roles of the highly conserved Swi5-Sfr1
accessory complex in yeast, mice and humans, and explore similarities and
differences between these species.
PMID- 28423186
TI - The dynamics of searching for meaning and presence of meaning in daily life.
AB - OBJECTIVE: Research on searching for meaning in life has focused on trait-level
relationships rather than within-person relationships. Our goal was to examine
within-person relationships between daily states of searching for meaning in
life, daily states of presence of meaning in life, and daily states of well
being. METHOD: To advance our understanding of searching for meaning in life, we
conducted a daily diary study with two samples in which 254 undergraduate
students (Mage = 18.54, SD = 1.55; 66.9% female) completed daily reports of
presence and search for meaning in life and well-being for 2 weeks (n = 3,288).
RESULTS: Between persons, search was negatively related to presence and well
being. In contrast, within persons, daily search was positively related to
presence and well-being. Relationships between daily search and daily well-being
were mediated by daily presence of meaning in life. Lagged analyses indicated
that greater search on one day led to greater presence the next day. CONCLUSIONS:
The implications of these within-person findings suggest that researchers should
reconsider the potential consequences that occur from searching for meaning in
life, including the possibility that greater searching is associated with
increased well-being.
PMID- 28423187
TI - Characterization of the binding capacity of mercurial species in Lactobacillus
strains.
AB - BACKGROUND: Metal sequestration by bacteria has been proposed as a strategy to
counteract metal contamination in foodstuffs. Lactobacilli can interact with
metals, although studies with important foodborne metals such as inorganic
[Hg(II)] or organic (CH3 Hg) mercury are lacking. Lactobacilli were evaluated for
their potential to bind these contaminants and the nature of the interaction was
assessed by the use of metal competitors, chemical and enzymatical treatments,
and mutants affected in the cell wall structure. RESULTS: Lactobacillus strains
efficiently bound Hg(II) and CH3 Hg. Mercury binding by Lactobacillus casei BL23
was independent of cell viability. In BL23, both forms of mercury were cell wall
bound. Their interaction was not inhibited by cations and it was resistant to
chelating agents and protein digestion. Lactobacillus casei mutants affected in
genes involved in the modulation of the negative charge of the cell wall anionic
polymer lipoteichoic acid showed increased mercury biosorption. In these mutants,
mercury toxicity was enhanced compared to wild-type bacteria. These data suggest
that lipoteichoic acid itself or the physicochemical characteristics that it
confers to the cell wall play a major role in mercury complexation. CONCLUSION:
This is the first example of the biosorption of Hg(II) and CH3 Hg in lactobacilli
and it represents a first step towards their possible use as agents for
diminishing mercury bioaccessibility from food at the gastrointestinal tract. (c)
2017 Society of Chemical Industry.
PMID- 28423185
TI - Functional identification of activity-regulated, high-affinity glutamine
transport in hippocampal neurons inhibited by riluzole.
AB - Glutamine (Gln) is considered the preferred precursor for the neurotransmitter
pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS.
Here, an activity-regulated, high-affinity Gln transport system is described in
developing and mature neuron-enriched hippocampal cultures that is potently
inhibited by riluzole (IC50 1.3 +/- 0.5 MUM), an anti-glutamatergic drug, and is
blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A
transport inhibitor. K+ -stimulated MeAIB transport displays an affinity (Km )
for MeAIB of 37 +/- 1.2 MUM, saturates at ~ 200 MUM, is dependent on
extracellular Ca2+ , and is blocked by inhibition of voltage-gated Ca2+ channels.
Spontaneous MeAIB transport is also dependent on extracellullar Ca2+ and voltage
gated calcium channels, but is also blocked by the Na+ channel blocker
tetrodotoxin, by Glu receptor antagonists, and by GABA indicating its dependence
on intact neural circuits driven by endogenous glutamatergic activity. The
transport of MeAIB itself does not rely on Ca2+ , but on Na+ ions, and is pH
sensitive. Activity-regulated, riluzole-sensitive spontaneous and K+ -stimulated
transport is minimal at 7-8 days in vitro, coordinately induced during the next 2
weeks and is maximally expressed by days in vitro > 20; the known period for
maturation of the Glu/Gln cycle and regulated pre-synaptic Glu release.
Competition analyses with various amino acids indicate that Gln is the most
likely physiological substrate. Activity-regulated Gln/MeAIB transport is not
observed in astrocytes. The functional identification of activity-regulated, high
affinity, riluzole-sensitive Gln/MeAIB transport in hippocampal neurons may have
important ramifications in the neurobiology of activity-stimulated pre-synaptic
Glu release, the Glu/Gln cycle between astrocytes and neurons, and neuronal Glu
induced excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.13805.
PMID- 28423188
TI - Intertrial interval duration affects error monitoring.
AB - The purpose of this study was to investigate the effect of varying intertrial
interval (ITI) durations on neural signals of error monitoring, given the
importance of the ITI as a time window for engaging in self-evaluation and
cognitive control. In a between-subjects design, 35 participants were assigned to
one of three ITI durations (short: 768 ms; medium: 1,280 ms; long: 1,792 ms) in a
standard Stroop task while EEG was recorded. Participants in the short-ITI group
demonstrated lower performance accuracy, a reduced error-related negativity (even
when correcting for frequency of errors), lower error-related alpha suppression
during the ITI, and increased post-error slowing. Results indicate that fast
paced trial timing can be disruptive to self-monitoring, perhaps due to capacity
limitations or bottlenecks in processing.
PMID- 28423190
TI - The clinical utility of genome-wide non invasive prenatal screening.
AB - OBJECTIVE: In this study, we expanded conventional cell-free fetal DNA (cfDNA)
based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed
to compare the performance of the two tests in a large general population of
pregnant women, in order to assess the clinical utility of the genome-wide
screening. METHOD: Genome-wide cfDNA analysis was offered to 12 114 pregnant
women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed
using an algorithm optimized to identify aneuploidies and subchromosomal
aberrations. RESULTS: Genome-wide screening allowed detection of 12 (7.4%)
potentially viable clinically relevant chromosomal abnormalities, which would
have remained overlooked if only conventional NIPT had been performed. This
resulted in a statistically significant higher sensitivity (100% vs 92.64%, p <
0.001) than did standard screening. This was achieved without sacrificing the
specificity of the test, which resulted similar to that obtained with standard
cfDNA testing (99.87% vs 99.77%, p = 0.064). CONCLUSION: Genome-wide cfDNA
analysis represents an enhanced screening tool for prenatal detection of
chromosomal abnormalities, allowing identification of clinically relevant
imbalances that are not detectable by conventional cfDNA testing. The results of
this study demonstrate the clinical utility of genome-wide cfDNA analysis. This
level of screening provides a significant higher sensitivity compared to standard
screening while maintaining a high specificity, with the potential to improve
overall pregnancy management. (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423189
TI - Computed tomography quantification of tracheal abnormalities in COPD and their
influence on airflow limitation.
AB - PURPOSE: To present a method to automatically quantify tracheal morphology
changes during breathing and investigate its contribution to airflow impairment
when adding CT measures of emphysema, airway wall thickness, air trapping and
ventilation. METHODS: Because tracheal abnormalities often occur localized, a
method is presented that automatically determines the most abnormal trachea
section based on automatically computed sagittal and coronal lengths. In this
most abnormal section, trachea morphology is encoded using four equiangular rays
from the center of the trachea and the normalized lengths of these rays are used
as features in a classification scheme. Consequently, trachea measurements are
used as input for classification into GOLD stages in addition to emphysema, air
trapping and ventilation. A database of 200 subjects distributed across all GOLD
stages is used to evaluate the classification with a k nearest neighbour
algorithm. Performance is assessed in two experimental settings: (a) when only
inspiratory scans are taken; (b) when both inspiratory and expiratory scans are
available. RESULTS: Given only an inspiratory CT scan, measuring tracheal shape
provides complementary information only to emphysema measurements. The best
performing set in the inspiratory setting was a combination of emphysema and
bronchial measurements. The best performing feature set in the inspiratory
expiratory setting includes measurements of emphysema, ventilation, air trapping,
and trachea. Inspiratory and inspiratory-expiratory settings showed similar
performance. CONCLUSIONS: The fully automated system presented in this study
provides information on trachea shape at inspiratory and expiratory CT. Addition
of tracheal morphology features improves the ability of emphysema and air
trapping CT-derived measurements to classify COPD patients into GOLD stages and
may be relevant when investigating different aspects of COPD.
PMID- 28423191
TI - Origins and evolution of innate lymphoid cells: Wardens of barrier immunity.
AB - The identification, in the late 2000s, of innate lymphoid cells (ILCs) as a new
class of non-B, non-T lymphocytes has led to global efforts to understand their
functions, plasticity and evolutionary origins and to define their place within
the leucocyte family. Although this work has uncovered striking similarities in
the developmental cues, lineage-specific transcription factors and functional
capacities of innate and adaptive lymphocytes, it has become clear that ILCs play
a unique and defining role as stewards of barrier defence and that this sets them
apart from their adaptive cousins. This review will explore how the dynamic
environment of barrier surfaces has shaped ILC evolution and functionality. We
highlight the critical importance of the microbiome and the unique role of ILCs
as environmental sensors. We reflect on how these factors may have influenced the
development of ILC2s and barrier immunity in the context of exposure to helminth
parasites that have been driving forces of our evolution throughout human
history. Finally, we argue that the plasticity of ILC function reflects their
role as first responders to environmental change.
PMID- 28423192
TI - Systematic Review of the Safety and Efficacy of Palivizumab among Infants and
Young Children with Cystic Fibrosis.
AB - BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen in infants
with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection
as the standard of care for infants with CF remains controversial. OBJECTIVE: To
evaluate the efficacy of palivizumab in reducing the incidence of RSV
hospitalization in children with CF who are younger than 2 years. METHODS: Four
electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from
inception until January 31, 2017, for clinical studies investigating the use of
palivizumab in infants with CF aged less than 2 years. The primary outcome was
hospitalization rate due to RSV infection. Secondary outcomes included
hospitalization for respiratory illness, length of hospital stay, safety (adverse
effects), and cost-effectiveness of palivizumab prophylaxis. RESULTS: The review
included a total of 10 studies (six cohort studies, two before-and-after studies,
one cross-sectional study, and one randomized controlled trial) involving 3891
patients with CF. Seven studies reported that palivizumab prophylaxis had a
positive impact on the rate of RSV hospitalization. Five studies (n=3404)
reported that palivizumab prophylaxis significantly reduced the rate of
hospitalization due to RSV infection compared to no prophylaxis. One study (n=5)
demonstrated patients with CF who received palivizumab had no RSV
hospitalization. Another study showed infants with CF receiving palivizumab
(n=117) had a lower risk of hospitalization for RSV infection compared with
premature infants (gestational age < 35 completed weeks) who received palivizumab
(n=4880). CONCLUSIONS: Evidence from the literature suggests that palivizumab may
have a potential role in reducing RSV hospitalization in children aged less than
2 years with CF. Given the lack of overall data, additional research is warranted
to better understand the efficacy and safety of prophylactic palivizumab in
infants with CF.
PMID- 28423193
TI - Is the use of differences in the magnitude of CAL gain appropriate for making
conclusions on the efficacy of non-surgical therapeutic means?
PMID- 28423195
TI - Noninvasive imaging of c(RGD)2 -9R as a potential delivery carrier for
transfection of siRNA in malignant tumors.
AB - The purpose of our study was to develop and evaluate a novel integrin alphav
beta3 -specific delivery carrier for transfection of siRNA in malignant tumors.
We adopted arginine-glycine-aspartate (RGD) motif as a tissue target for specific
recognition of integrin alphanu beta3 . A chimaeric peptide was synthesized by
adding nonamer arginine residues (9-arginine [9R]) at the carboxy terminus of
cyclic-RGD dimer, designated as c(RGD)2 -9R, to enable small interfering RNA
(siRNA) binding. To test the applicability of the delivery carrier in vivo,
c(RGD)2 -9R was labeled with radionuclide of technetium-99m. Biodistribution and
gamma-camera imaging studies were performed in HepG2 xenograft-bearing nude mice.
As results, an optimal 10:1 molar ratio of 99m Tc-c(RGD)2 -9R to siRNA was
indicated by the electrophoresis on agarose gels. 99m Tc-c(RGD)2 -9R/siRNA
remained stable under a set of conditions in vitro. For in vivo study, tumor
radioactivity uptake of 99m Tc-c(RGD)2 -9R/siRNA in nude mice bearing HepG2
xenografts was significantly higher than that of control probe (P < .05). The
xenografts were clearly visualized at 4 hours till 6 hours noninvasively after
intravenous injection of 99m Tc-c(RGD)2 -9R/siRNA, while the xenografts were not
visualized at any time after injection of control probe. It was concluded that
c(RGD)2 -9R could be an effective siRNA delivery carrier. Technetium-99m
radiolabeled-delivery carrier represents a potential imaging strategy for RNAi
based therapy.
PMID- 28423196
TI - Melatonin enhances neural stem cell differentiation and engraftment by increasing
mitochondrial function.
AB - Neural stem cells (NSCs) are regarded as a promising therapeutic approach to
protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such
as Parkinson's disease and Alzheimer's disease (PD and AD, respectively).
However, new research suggests that NSC differentiation is required to make this
strategy effective. Several studies have demonstrated that melatonin increases
mature neuronal markers, which reflects NSC differentiation into neurons.
Nevertheless, the possible involvement of mitochondria in the effects of
melatonin during NSC differentiation has not yet been fully established. We
therefore tested the impact of melatonin on NSC proliferation and differentiation
in an attempt to determine whether these actions depend on modulating
mitochondrial activity. We measured proliferation and differentiation markers,
mitochondrial structural and functional parameters as well as oxidative stress
indicators and also evaluated cell transplant engraftment. This enabled us to
show that melatonin (25 MUM) induces NSC differentiation into oligodendrocytes
and neurons. These effects depend on increased mitochondrial mass/DNA/complexes,
mitochondrial respiration, and membrane potential as well as ATP synthesis in
NSCs. It is also interesting to note that melatonin prevented oxidative stress
caused by high levels of mitochondrial activity. Finally, we found that melatonin
enriches NSC engraftment in the ND mouse model following transplantation. We
concluded that a combined therapy involving transplantation of NSCs pretreated
with pharmacological doses of melatonin could efficiently restore neuronal cell
populations in PD and AD mouse models depending on mitochondrial activity
promotion.
PMID- 28423197
TI - Diabetic kidney transplant recipients: Impaired infection control and increased
alloreactivity.
AB - BACKGROUND: Post-transplantation diabetes mellitus (PTDM) has been associated
with inferior patient and allograft outcomes. However, previous studies did not
identify differences in infection control and alloreactivity. METHODS: We studied
449 kidney transplant recipients (KTRs) between 2005 and 2013. Fifty (11.1%) KTRs
were diagnosed with PTDM and 60 (13.4%) KTRs with pre-existing diabetes. Samples
were collected pretransplantation, at +1, +2, +3 months post-transplantation. CMV
specific and alloreactive T cells were quantified by interferon-gamma Elispot
assay. Lymphocyte subpopulations were quantified by flow cytometry. RESULTS: Upon
multivariate analysis, age, obesity, and the use of tacrolimus increased the risk
of PTDM (P<.05). KTRs with pre-existing diabetes/PTDM showed higher rates of
sepsis (P<.01). Total CD3+ and CD4+ T cell counts were significantly lower in
KTRs with PTDM/pre-existing diabetes post-transplantation (P<.05). No differences
were observed for CMV-specific T cells between any group (P>.05). KTRs developing
PTDM showed increased frequencies of alloreactive T-cells post-transplantation
(P<.05). CONCLUSIONS: Our results suggest higher rates of infection in KTRs with
pre-existing diabetes/PTDM that may be attributed to impaired overall immunity.
Higher frequencies of alloreactive T cells contribute to inferior long-term
outcomes. As acute rejection, but not pre-existing diabetes/PTDM, was associated
with inferior allograft survival and function, maintaining adequate
immunosuppression to prevent rejection seems important.
PMID- 28423199
TI - Chemical Synthesis of Modified Hyaluronic Acid Disaccharides.
AB - Herein we report a chemical synthesis towards new modified hyaluronic acid
oligomers by using only commercially available d-glucose and d-glucosamine
hydrochloride. The various protected hyaluronic acid disaccharides were
synthesized bearing new functional groups at C-6 of the beta-d-glucuronic acid
moiety with a view to structure-related biological activity tests. The orthogonal
protecting group pattern allows ready access to the corresponding higher
oligomers. Also, 1 H NMR studies of the new derivatives demonstrated the effect
of the various functional groups on the intramolecular electronic environment.
PMID- 28423198
TI - An estradiol-inducible promoter enables fast, graduated control of gene
expression in fission yeast.
AB - The fission yeast Schizosaccharomyces pombe lacks a diverse toolkit of inducible
promoters for experimental manipulation. Available inducible promoters suffer
from slow induction kinetics, limited control of expression levels and/or a
requirement for defined growth medium. In particular, no S. pombe inducible
promoter systems exhibit a linear dose-response, which would allow expression to
be tuned to specific levels. We have adapted a fast, orthogonal promoter system
with a large dynamic range and a linear dose response, based on beta-estradiol
regulated function of the human oestrogen receptor, for use in S. pombe. We show
that this promoter system, termed Z3 EV, turns on quickly, can reach a maximal
induction of 20-fold, and exhibits a linear dose response over its entire
induction range, with few off-target effects. We demonstrate the utility of this
system by regulating the mitotic inhibitor Wee1 to create a strain in which cell
size is regulated by beta-estradiol concentration. This promoter system will be
of great utility for experimentally regulating gene expression in fission yeast.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423200
TI - CD80CD86 deficiency disrupts regulatory CD4+FoxP3+T cell homoeostasis and induces
autoimmune-like alopecia.
AB - Alopecia areata (AA) is an autoimmune disease that results in spot baldness in
humans. Adequate animal models for AA are currently lacking. The objective of
this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in
C57BL/6.CD80CD86-deficient (B6.CD80CD86-/- ) mice. Incidence and severity of
alopecia were analysed in 58 B6.CD80CD86-/- mice using histological examination,
flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR
and CD25 inhibition test. Both male and female B6.CD80CD86-/- mice showed almost
100% incidence of hair loss at 40 weeks of age. Moreover, CD4+FoxP3+Treg (Treg)
cell population in B6.CD80CD86-/- mice was significantly lower than in B6 mice,
which presumably underlined autoimmune reaction. Histologically, B6.CD80CD86-/-
mice showed CD4+ and CD8+ T-cell infiltration around terminal follicle region and
exhibited hair follicle destruction in the anagen or catagen stage. Negative
correlation between the number of CD4+FoxP3+ Tregs and ALA was confirmed by the
CD25 depletion test in B6 mice, as follicle destruction was similar to that
observed in B6.CD80CD86-/- animals. CD80CD86 deficiency disrupted CD4+FoxP3+ Treg
homoeostasis and prompted the development of ALA. We demonstrated that
B6.CD80CD86-/- mice might have several advantages as an ALA model, because they
exhibited high incidence of disease phenotype and epipathogenesis similar to that
observed in human AA.
PMID- 28423201
TI - Highly Enantioselective Allylation of Ketones: An Efficient Approach to All
Stereoisomers of Tertiary Homoallylic Alcohols.
AB - An optimized protecting group for allylboronates allowed the use of ketones in
order to synthesize all isomers of quaternary homoallylic alcohols with high
enantioselectivities. All symmetric isomers of the allylboronate were prepared in
high yields and diastereoselectivities using Sn 2' reactions. The improved
reactivity of the novel protecting group was verified by following the reaction
kinetics with 1 H NMR spectroscopy. Mechanistic studies using DFT calculations
were conducted to investigate the new findings. Thus, the stereochemical outcome
and enhanced reactivity can be rationalized.
PMID- 28423202
TI - In some places, in some cases, and at some times, harmful algal blooms are the
greatest threat to inland water quality.
PMID- 28423203
TI - Corrigendum.
PMID- 28423204
TI - New Motifs in Deoxydehydration: Beyond the Realms of Rhenium.
AB - The deoxydehydration (DODH) reaction remains one of the most efficient methods of
reducing the oxygen content of biomass while keeping important functionality in
place. This reaction is traditionally catalysed by high-valent oxo-rhenium
species. Recent research into heterogeneous rhenium-based catalysts for DODH
demonstrates their ability to rival and in some cases surpass their homogeneous
counterparts. Furthermore, catalysts based on the metals molybdenum and vanadium
show great potential as inexpensive alternatives to rhenium catalysts. In this
Minireview, we detail the recent developments within the field of DODH with
particular emphasis on discoveries outside the realms of rhenium.
PMID- 28423206
TI - Folic acid - Who does what with methotrexate?
PMID- 28423205
TI - The impact of biogas and fuelwood use on institutional kitchen air quality in
Kampala, Uganda.
AB - Experts have suggested that microscale biogas systems offer a source of renewable
energy that improves indoor air quality, but such impacts have not been directly
measured. This study documented cooking behaviors and measured 2.5-MUm
particulate matter (PM2.5 ), carbon monoxide (CO), and sulfur dioxide (SO2 )
concentrations within 14 institutional kitchens in Kampala, Uganda, that prepare
meals using biogas (n=5), a mixture of biogas and fuelwood (n=3), and fuelwood
(n=6). Small institutions (10-30 people) with biogas kitchens had 99% lower
concentrations of PM2.5 (21 MUg/m3 ) than fuelwood kitchens (3100 MUg/m3 ).
Larger institutions (>100 people) had biogas systems that produced insufficient
gas and relied on fuelwood to meet over 90% of their energy needs. PM2.5
concentrations in these biogas-firewood kitchens were equivalent to
concentrations in fuelwood kitchens. Although concentrations of hydrogen sulfide
(H2 S) in biogas were as high as 2000 ppm, 75% of systems had undetectable H2 S
levels (<100 ppm) in the biogas. Kitchens using biogas with high H2 S had
correspondingly higher SO2 concentrations in the kitchen air. However, even the
highest SO2 concentration in biogas kitchens (150 MUg/m3 ) was lower than SO2
concentration in fuelwood kitchens (390 MUg/m3 ). The results suggest that biogas
systems can offer air quality improvements if sized properly for energy demands.
PMID- 28423207
TI - Nanospray liquid chromatography/tandem mass spectrometry analysis of steroids
from gray whale blubber.
AB - RATIONALE: Analysis of steroids from precious blubber biopsies obtained from
marine mammals, especially endangered species, can provide valuable information
on their endocrine status. Challenges with currently used ELISA methodology
include lack of absolute quantitation and incompatibility with multiple steroids
analysis due to limited biopsy mass. Development of a sensitive, accurate
analytical method for this purpose is critical. METHODS: A nanospray liquid
chromatography/tandem mass spectrometry (nanoLC/MS/MS) method was validated for
sensitive, specific and quantitative analysis of three steroid hormones, without
derivatization, extracted from 50 mg blubber samples. Data was acquired with an
LTQ XL ion trap mass spectrometer in positive ion mode, using single reaction
monitoring. All three steroids were analyzed in a single run. Cholic acid was
used as a surrogate internal standard for quantitation due to its steroidal
structure and lack of measurable endogenous levels in blubber. RESULTS: The
lowest limits of quantitation for progesterone, testosterone, and hydrocortisone
were significantly improved compared to previous studies using conventional
LC/MS/MS. The lowest limit of detection was 7 fg/MUL using a 1 MUL injection
volume. Calibration curves for steroid quantification showed good linearity (r2
>0.99) between 14 and 3620 fg/MUL, and accuracy was <20% for interday and <10%
for intraday. After validation, the method was successfully applied to
quantification of steroids in gray whale blubber samples. CONCLUSIONS: The
nanoLC/MS/MS method is more sensitive than traditional LC/MS/MS for steroid
analysis. It is also compatible with other important biopsy analyses due to its
small blubber mass requirement. This will benefit the reproductive and stress
assessments for all marine mammals, particularly endangered populations.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423208
TI - Combined activity of temozolomide and the mTOR inhibitor temsirolimus in
metastatic melanoma involves DKK1.
AB - The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in
patients with BRAF-mutant melanoma, but its effects are limited by the onset of
drug resistance. In the case of resistance, chemotherapy can still be applied as
second line therapy. However, it yields low response rates and strategies are
urgently needed to potentiate its effects. In a previous study, we showed that
the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity
of melanoma cells to chemotherapeutic drugs (J. Invest. Dermatol. 2009, 129,
1500). In this study, the combination of the mTOR inhibitor temsirolimus with the
chemotherapeutic agent temozolomide significantly increases growth inhibition and
apoptosis in melanoma cells compared to temsirolimus or temozolomide alone. The
combination of temozolomide with temsirolimus is not only effective in
established but also in newly isolated and vemurafenib-resistant metastatic
melanoma cell lines. These effects are associated with the downregulation of the
anti-apoptotic protein Mcl-1 and the upregulation of the Wnt antagonist Dickkopf
homologue 1 (DKK1). Knock-down of DKK1 suppresses apoptosis induction by the
combination of temsirolimus and temozolomide. These data suggest that the
inhibition of the mTOR pathway increases sensitivity of melanoma cells towards
temozolomide. Chemosensitisation is associated with enhanced expression of the
Wnt antagonist DKK1.
PMID- 28423209
TI - The R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and
vacuolar acidification in apple.
AB - Malate, the predominant organic acid in many fruits, is a crucial component of
the organoleptic quality of fruit, including taste and flavor. The genetic and
environmental mechanisms affecting malate metabolism in fruit cells have been
studied extensively. However, the transcriptional regulation of malate
metabolizing enzymes and vacuolar transporters remains poorly understood. Our
previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and
vacuolar acidification by directly activating vacuolar transporters, including
MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a
MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It
was subsequently found that MdMYB73 protein bound directly to the promoters of
MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase
subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating
their expression and thereby enhancing their activities. Analyses of transgenic
apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar
pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon
downstream target genes. These findings help to elucidate how MdMYB73 directly
modulates the vacuolar transport system to affect malate accumulation and
vacuolar pH in apple.
PMID- 28423210
TI - Intrinsic incompatibilities evolving as a by-product of divergent ecological
selection: Considering them in empirical studies on divergence with gene flow.
AB - The possibility of intrinsic barriers to gene flow is often neglected in
empirical research on local adaptation and speciation with gene flow, for example
when interpreting patterns observed in genome scans. However, we draw attention
to the fact that, even with gene flow, divergent ecological selection may
generate intrinsic barriers involving both ecologically selected and other
interacting loci. Mechanistically, the link between the two types of barriers may
be generated by genes that have multiple functions (i.e., pleiotropy), and/or by
gene interaction networks. Because most genes function in complex networks, and
their evolution is not independent of other genes, changes evolving in response
to ecological selection can generate intrinsic barriers as a by-product. A
crucial question is to what extent such by-product barriers contribute to
divergence and speciation-that is whether they stably reduce gene flow. We
discuss under which conditions by-product barriers may increase isolation.
However, we also highlight that, depending on the conditions (e.g., the amount of
gene flow and the strength of selection acting on the intrinsic vs. the
ecological barrier component), the intrinsic incompatibility may actually
destabilize barriers to gene flow. In practice, intrinsic barriers generated as a
by-product of divergent ecological selection may generate peaks in genome scans
that cannot easily be interpreted. We argue that empirical studies on divergence
with gene flow should consider the possibility of both ecological and intrinsic
barriers. Future progress will likely come from work combining population genomic
studies, experiments quantifying fitness and molecular studies on protein
function and interactions.
PMID- 28423211
TI - "Driving to the edge of the cliff": Transgender mental health.
PMID- 28423212
TI - Persistent Radicals of Self-assembled Benzophenone bis-Urea Macrocycles:
Characterization and Application as a Polarizing Agent for Solid-state DNP MAS
Spectroscopy.
AB - UV-irradiation of a self-assembled benzophenone bis-urea macrocycle generates MUm
amounts of radicals that persist for weeks under ambient conditions. High-field
EPR and variable-temperature X-band EPR studies suggest a resonance stabilized
radical pair through H-abstraction. These endogenous radicals were applied as a
polarizing agent for magic angle spinning (MAS) dynamic nuclear polarization
(DNP) NMR enhancement. The field-stepped DNP enhancement profile exhibits a sharp
peak with a maximum enhancement of epsilonon/off =4 superimposed on a nearly
constant DNP enhancement of epsilonon/off =2 over a broad field range. This
maximum coincides with the high field EPR absorption spectrum, consistent with an
Overhauser effect mechanism. DNP enhancement was observed for both the host and
guests, suggesting that even low levels of endogenous radicals can facilitate the
study of host-guest relationships in the solid-state.
PMID- 28423213
TI - Systemic tumor-targeted sodium iodide symporter (NIS) gene therapy of
hepatocellular carcinoma mediated by B6 peptide polyplexes.
AB - BACKGROUND: Nonviral polymer-based gene transfer represents an adaptable system
for tumor-targeted gene therapy because various design strategies of shuttle
systems, together with the mechanistic concept of active tumor targeting, lead to
improved gene delivery vectors resulting in higher tumor specificity, efficacy
and safety. METHODS: Using the sodium iodide symporter (NIS) as a theranostic
gene, nonviral gene delivery vehicles based on linear polyethylenimine (LPEI),
polyethylene glycol (PEG) and coupled to the synthetic peptide B6 (LPEI-PEG-B6),
which specifically binds to tumor cells, were investigated in a hepatocellular
carcinoma xenograft model for tumor selectivity and transduction efficiency.
RESULTS: In vitro incubation of three different tumor cell lines with LPEI-PEG
B6/NIS resulted in significant increase in iodide uptake activity compared to
untargeted and empty vectors. After establishment of subcutaneous HuH7 tumors,
NIS-conjugated nanoparticles were injected intravenously followed by analysis of
radioiodide biodistribution using 123 I-scintigraphy showing significant
perchlorate-sensitive iodide accumulation in tumors of LPEI-PEG-B6/NIS-treated
mice (8.0 +/- 1.5% ID/g 123 I; biological half-life of 4 h). After four cycles of
repetitive polyplex/131 I applications, a significant delay of tumor growth was
observed, which was associated with markedly improved survival in the therapy
group. CONCLUSIONS: These results clearly demonstrate that systemic in vivo NIS
gene transfer using nanoparticle vectors coupled to B6 tumor targeting ligand is
capable of inducing tumor-specific radioiodide uptake. This promising gene
therapy approach opens the exciting prospect of NIS-mediated radionuclide therapy
in metastatic cancer, together with the possibility of combining several
targeting ligands to enhance selective therapeutic efficacy in a broad field of
cancer types with various receptor expression profiles.
PMID- 28423214
TI - Plasmodium falciparum OTU-like cysteine protease (PfOTU) is essential for
apicoplast homeostasis and associates with noncanonical role of Atg8.
AB - The metabolic pathways associated with the mitochondrion and the apicoplast in
Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as
suitable drug targets. In the present study, we have identified functional role
of a novel ovarian tumour unit (OTU) domain-containing cysteine protease of
Plasmodium falciparum (PfOTU). A C-terminal regulatable fluorescent affinity tag
on native protein was utilised for its localization and functional
characterization. Detailed studies showed vesicular localization of PfOTU and its
association with the apicoplast. Degradation-tag mediated knockdown of PfOTU
resulted in abnormal apicoplast development and blocked development of parasites
beyond early-schizont stages in subsequent cell cycle; downregulation of PfOTU
hindered apicoplast protein import. Further, the isoprenoid precursor-mediated
parasite growth-rescue experiments confirmed that PfOTU knockdown specifically
effect development of functional apicoplast. We also provide evidence for a
possible biological function of PfOTU in membrane deconjugation of Atg8, which
may be linked with the apicoplast protein import. Overall, our results show that
the PfOTU is involved in apicoplast homeostasis and associates with the
noncanonical function of Atg8 in maintenance of parasite apicoplast.
PMID- 28423215
TI - Breaking down the stigma of mental health nursing: A qualitative study reflecting
opinions from western australian nurses.
AB - WHAT IS KNOWN ON THE SUBJECT?: The rate of mental illness in the general
population is ever increasing Mental health nurses are ageing, and this is not a
preferred career for new graduates; thus, recruitment and retention of mental
health nurses is declining Stigma is attached to the view of mental illness and
the role of a mental health nurse. If this stigma can be reduced, it may provide
an opportunity for the profession to become more popular and assist recruitment
in this area WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Previous research has
focused on why mental health nurses leave the profession which has not provided
successful results This study adopts a new way of working whereby we gathered
opinions from current mental health nurses focusing on why they originally wanted
to work in mental health WHAT ARE THE IMPLICATIONS FOR PRACTICE?: New findings
presented in this paper will guide improvements in nurse training, policy
development for mental health services and improve recruitment of the next
generation of mental health nurses The findings provide a strong message that in
order to entice others to work in mental health, we need to first address
breaking down the stigma related to mental health nursing ABSTRACT: Introduction
A lack of understanding surrounding the role of mental health nursing is
associated with recruitment and retention challenges. Additional complexities
include stigma related to the role, an ageing workforce and dearth of graduates
keen to pursue this career. Scientific Rational Previous research has focused on
why nurses leave the profession which has not provided necessary solutions. There
is a need to instead explore why nurses originally chose a career in mental
health. Aim of study This qualitative study focused on opinions and experiences
of existing mental health nurses to determine what could be performed to entice
nurses to choose mental health. Methods A cross-sectional design involving a
brief interview was conducted with 192 Western Australian nurses from one public
mental health service. Results Thematic analysis revealed an overarching theme
"breaking down stigma" and additional themes of: "visibility of mental health
nursing" and "growing mental health nursing." Subthemes under "visibility"
included "self-promotion" plus "industry and university promotion," whereas
subthemes related to "growing" focused upon "improving the student experience."
Finally, "recognizing the mental health specialty" was identified for an
attractive career pathway. Discussion This study adds to international evidence
and showcases unique insights from mental health nurses into why they chose a
career in mental health whilst previously replicated research focused on why
nurses chose to leave. Implications for practice Findings suggest that before we
can entice nurses to choose mental health, there is urgency to reduce stigma
related to the role. "Breaking down stigma" will allow the role to become more
visible and be represented in a more positive authentic manner. New findings in
this paper will drive improvements of future nurse education, policy planning and
recruitment design for the next generation of mental health nurses.
PMID- 28423216
TI - Tokenistic or genuinely effective? Exploring the views of voluntary sector staff
regarding the emerging peer support worker role in mental health.
AB - WHAT IS KNOWN ON THE SUBJECT: The introduction of PSWs within mental health
services has grown substantially both internationally and locally; however, no
recognized studies have focused on the evolvement of this role within a Northern
Ireland (NI) context. Research is increasingly focusing on service users' and
PSWs perspectives on mental health service provision. Despite this, few studies
exist which exclusively report staff views in relation to the PSW role. WHAT THE
PAPER ADDS TO EXISTING KNOWLEDGE: Results of the current study identified varying
perspectives on the peer role. Some participants believed that the PSW role was
tokenistic; others opposed these views, highlighting the value of this role.
Clearly defined job descriptions and the importance of ensuring the PSW is a
cohesive part of the team and not an "add on," was identified as imperative to
avoid tokenistic practice. Provision of a flexible working environment, both
sensitive and responsive to the peers' own mental health needs, was identified as
significant in order for the peer to fulfil their role successfully. IMPLICATIONS
FOR PRACTICE: Services introducing PSWs within teams should engage with nursing
staff at all organizational levels in the role development process to minimize
the risk of tokenism, for example, the PSW role not integrated or valued within
teams. Clearly defined job/role specifications for PSWs should be devised to
ensure that both the PSW and the mental health nursing team have a shared
understanding regarding this role. ABSTRACT: Aim Peer support worker (PSW) roles
are gaining recognition internationally as a valuable component in mental health
service delivery. The aim of this study was to explore the views of mental health
voluntary sector staff regarding the emergence of this role. Method A qualitative
research design was used. A purposive sample was employed. Semi-structured
interviews were undertaken with 10 staff members in various positions in two
voluntary mental health organizations. Interview transcripts were analysed
thematically. Results Views varied on the PSW role with some participants stating
that it was tokenistic, whereas others highlighted the value of its contribution.
Participants' expressed concerns regarding professional boundaries and
organizational cultural challenges that PSWs may encounter in their role. The
provision of reasonable adjustments was recommended as an integral support
mechanism. Conclusion Successful integration of the PSW requires careful
consideration of the role, the workplace environment and the unique needs of the
peer, to prevent the role becoming constrained and diluted. Implications for
practice The PSW role may impact the traditional delivery of mental health
nursing services. It is therefore essential that nurses are cognizant of these
potential challenges to successfully facilitate the integration of PSWs in
practice.
PMID- 28423217
TI - In-vitro discrimination of wound associated bacteria by volatile compound
profiling using Selected Ion Flow Tube - Mass Spectrometry.
AB - AIMS: To determine if bacterial species responsible for clinically relevant wound
infection produce specific volatile profiles that would allow their speciation.
METHODS AND RESULTS: Selected-Ion Flow Tube-Mass Spectrometry in full mass scan
mode was used to analyse headspace gases produced by wound-associated bacteria
grown in vitro, so as to enable identification of bacterial volatile product ion
profiles in the resulting mass spectra. Applying multivariate statistical
analysis (hierarchical clustering and principal component analysis) to the
resultant mass spectra enabled clear speciation. Moreover, bacterial volatile
product ions could be detected from artificially contaminated wound dressing
material, although the pattern of product ions detected was influenced by culture
conditions. CONCLUSIONS: Using selected product ions from the SIFT-MS mass
spectra it is possible to discriminate wound-associated bacterial species grown
under specific in vitro culture conditions. This article is protected by
copyright. All rights reserved.
PMID- 28423218
TI - Strain specific variation in plant growth promoting volatile organic compound
production by five different Pseudomonas spp. as confirmed by response of Vigna
radiata seedlings.
AB - AIM: Analysis of blend of volatile organic compounds (VOCs) released by
Pseudomonas spp. with growth promoting effect in Vigna radiata seedlings. METHODS
AND RESULTS: Plant growth promoting activity of VOCs produced by five different
Pseudomonas spp. was investigated by I-plate technique. VOCs produced by
different organisms were extracted by various solvents (methanol, ethyl acetate,
hexane and butanol) were identified by gas chromatography-mass spectrometric (GC
MS) analysis. The major VOCs identified were undecane, nonadecane, hexacosane,
tetradecane, heptacosane, pentadecane, dodecane and tetratetracontane. The
cultural conditions for the production of VOCs with plant growth enhancement
effect were optimized and further confirmed using pure pentadecane as a candidate
VOC. CONCLUSIONS: The study provides insight into plant beneficial effect of VOCs
produced by Pseudomonas spp. Remarkable modulation in production of VOCs with
plant growth promoting effect by rhizobacteria was found to be depend on
bacterial strain and its concentration. This article is protected by copyright.
All rights reserved.
PMID- 28423219
TI - 2017 American Transplant Congress Abstracts.
PMID- 28423220
TI - Gas-phase fragmentations of N-methylimidazolidin-4-one organocatalysts.
AB - N-methylimidazolidin-4-one organocatalysts were studied in the gas phase.
Protonated and sodium-cationized (sodiated) molecules are conveniently accessible
by electrospray mass spectrometry. Protonation enables three different closed
shell paths of ring cleavage leading to iminium ions. The fragmentation pattern
is largely unaffected by exocyclic substituents and thus is valuable to
characterize the substance type as N-methylimidazolidin-4-ones. Sodiated species
show a distinctly different fragmentation that is less useful for
characterization purposes: apart from signal loss due to dissociation of Na+ ,
the observation of benzyl radical loss is by far predominant. Only in absence of
a benzyl substituent, an analogue of the third ring cleavage (loss of [C2 H5 NO])
is observed. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28423221
TI - Facial asymmetry in head and neck rhabdomyosarcoma survivors.
AB - INTRODUCTION: Radiotherapy is essential for achieving and maintaining local
control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy
may cause outgrowth disturbances of facial bone and soft tissue, resulting in
facial asymmetry. The aim of this study was to develop a method to visualize and
measure facial asymmetry in HNRMS survivors using three-dimensional (3D) imaging
techniques. METHODS: Facial deformity was evaluated in a multidisciplinary
clinical assessment of 75 HNRMS survivors, treated with external beam
radiotherapy (EBRT, n = 26) or Ablative surgery, MOulage brachytherapy, and
REconstruction (AMORE, n = 49). Individual facial asymmetry was measured using 3D
photogrammetry and expressed in a raw asymmetry index and a normalized sex-age
ethnicity-matched asymmetry signature weight. Facial asymmetry was also compared
between British and Dutch controls and between survivors and their matched
controls. RESULTS: Facial asymmetry was more pronounced with increasing age (P <
0.01) in British controls compared with Dutch controls (P = 0.04). Survivors
developed more facial asymmetry than matched controls (P < 0.001). The clinical
assessment of facial deformity correlated with the raw asymmetry index (r = 0.60,
P < 0.001). DISCUSSION: 3D imaging can be used for objective measurement of
facial asymmetry in HNRMS survivors. The raw asymmetry index correlated with a
clinical assessment of facial deformity. Comparisons between treatment groups
seemed inappropriate given the differences in facial asymmetry between British
and Dutch controls. In future studies, pretreatment images could act as matched
controls for posttreatment evaluation.
PMID- 28423222
TI - Persistent and Developing Sleep Problems: A Prospective Cohort Study on the
Relationship to Poor Outcome in Patients Attending a Pain Clinic with Chronic Low
Back Pain.
AB - Sleep problems are common in people with low back pain (LBP); however, the
mechanisms of how sleep influences pain are complex. To date there is a lack of
prospective research on the timing and development of sleep problems in those who
have LBP; such information would be useful to identify individuals at risk for
poor outcomes. Our aims are to investigate the predictive role of sleep problems
on self-report recovery and pain intensity using logistic regression reporting
odds ratios (ORs). An observational cohort of 761 chronic LBP patients recruited
from a pain management clinic participated, and they completed data at baseline
and at 6-month follow-up (n = 682). Results show increased odds for reported
nonrecovery (OR 1.52) and pain intensity (OR 2.69) among those who reported sleep
problems at baseline. Further analysis on the experience of sleep problems
through time showed that those with developing sleep problems (ie, no sleep
problems at baseline but reported sleep problems at follow-up) were at increased
odds for reporting nonrecovery (OR 2.17) and pain intensity (OR 2.95), as were
those who reported sleep problems at both baseline and follow-up, for recovery
(OR 2.88) and pain intensity (OR 3.45). Those with resolving sleep problems (ie,
sleep problems present at baseline but not at follow-up) were at decreased odds
for nonrecovery (OR 0.50) and pain intensity (0.49). Presenting, persistent, and
developing sleep problems have a significant impact on recovery for those with
LBP. Clinicians may wish to consider treatment options that can address sleep
problems.
PMID- 28423223
TI - Implementation and preliminary effectiveness of a real-time pain management
smartphone app for adolescents with cancer: A multicenter pilot clinical study.
AB - BACKGROUND: Pain in adolescents with cancer (12-18 years) is common and
negatively impacts health-related quality of life (HRQL). The Pain Squad+
smartphone app, which provides adolescents with real-time pain self-management
support, was developed to address this issue. This study evaluated the
implementation of the app to inform a future randomized controlled trial (RCT)
and obtain treatment effect estimates for pain intensity, pain interference,
HRQL, and self-efficacy. PROCEDURE: A one-group baseline/poststudy design with 40
adolescents recruited from two pediatric tertiary care centers was used. Baseline
questionnaires were completed and adolescents used the app at least twice daily
for 28 days, receiving algorithm-informed self-management advice depending on
their reported pain. A nurse received alerts in response to sustained pain and
contacted adolescents to assist in pain care. Poststudy questionnaires were
completed. Descriptive analyses, with exploratory inferential testing conducted
on health outcome data, were used to address study aims. RESULTS: Most (40/52;
77%) eligible adolescents participated. Two participants withdrew participation.
Intervention fidelity was impacted by technical difficulties (occurring for 15%
of participants) and a prolonged time for nurse contact in the event of sustained
pain. Adherence to pain reporting was 68.8 +/- 38.1%. Outcome measure completion
rates were high and the intervention was acceptable to participants. Trends in
improvements in pain intensity, pain interference, and HRQL were significant,
with effect sizes of 0.23-0.67. CONCLUSIONS: Implementation of Pain Squad+ is
feasible and the app appears to improve pain-related outcomes for adolescents
with cancer. A multicenter RCT will be undertaken to examine app effectiveness.
PMID- 28423224
TI - Facial and extrafacial involvement of lupus miliaris disseminatus faciei with
Kaposi's sarcoma-like lesions.
PMID- 28423225
TI - Exercise interventions for patients with pediatric cancer during inpatient acute
care: A systematic review of literature.
AB - Physical inactivity has been shown to exacerbate negative side effects
experienced by pediatric patients undergoing cancer therapy. Exercise
interventions are being created in response. This review summarizes current
exercise intervention data in the inpatient pediatric oncology setting. Two
independent reviewers collected literature from three databases, and analyzed
data following the PRISMA statement for systematic reviews and meta-analyses. Ten
studies were included, representing 204 patients. Good adherence, positive trends
in health status, and no adverse events were noted. Common strategies included
individual, supervised, combination training with adaptability to meet
fluctuating patient abilities. We recommend that general physical activity
programming be offered to pediatric oncology inpatients.
PMID- 28423226
TI - RVX 208: A novel BET protein inhibitor, role as an inducer of apo A-I/HDL and
beyond.
AB - Low-density cholesterol (LDL) has been the prime target of currently available
lipid-lowering therapies although current research is expanding the focus beyond
LDL lowering and has included high-density cholesterol (HDL) also as the target.
Bromo and extra-terminal (BET) proteins are implicated in the regulation of
transcription of several regulatory genes and regulation of proinflammatory
pathways. As atherosclerosis is an inflammatory pathway and studies showed that
BET inhibition has a role in inhibiting inflammation, the concept of BET
inhibition came in the field of atherosclerosis. RVX 208 is a novel, orally
active, BET protein inhibitor and the only BET inhibitor currently available in
the field of atherosclerosis. RVX 208 acts primarily by increasing apo A-I
(apolipoprotein A-I) and HDL levels. RVX 208 has a novel action of increasing
larger, more cardio-protective HDL particles. Post hoc analysis of Phase II
trials also showed that RVX 208 reduced major adverse cardiovascular events
(MACE) in treated patients, over and above that of apo A-I/HDL increasing action.
This MACE reducing actions of RVX 208 were largely due to its novel anti
inflammatory actions. Currently, a phase III trial, BETonMACE, is recruiting
patients to look for the effects of RVX 208 in patients with increased risk of
atherosclerotic cardiovascular disease. So BET inhibitors act in multiple ways to
inhibit and modulate atherosclerosis and would be an emerging and potential
option in the management of multifactorial disease like coronary artery disease
by inhibiting a single substrate. But we need long-term phase III trial data's to
look for effects on real-world patients.
PMID- 28423227
TI - A national survey of screening and management of hypogammaglobulinemia in
Canadian transplantation centers.
AB - BACKGROUND: Infection remains one of the most common transplant-related causes of
death in patients undergoing transplantation. Secondary hypogammaglobulinemia
(HGG) as a component of immune suppression and deficiency is associated with both
solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT).
Available data and clinical experience for the supplementation of immunoglobulin
(Ig) in these patients is conflicting, and differing clinical opinion accounts
for non-uniform practice in the use of Ig treatment. We aimed to survey lead
transplant practitioners for current practice around polyvalent Ig use in post
transplant recipients across Canada. METHODS: We performed a survey study using
short questionnaires to estimate rate of screening of HGG, use of polyvalent Ig,
and physician's opinion on Ig treatment and infection prevention. Directors of 24
SOT and 23 HCT centers across Canada were invited to participate in the survey
via an electronic mail. RESULTS: Overall response rate was 63.8%. Twenty percent
of SOT programs routinely measured Ig levels pre-transplant compared to 33% of
allogeneic (allo-) and 21% of autologous (auto-) HCT programs. Post-transplant Ig
levels were measured in 13%, 75%, and 29% in SOT, allo-HCT, and auto-HCT,
respectively. The SOT and auto-HCT groups indicated that they do not prescribe Ig
therapy (100% and 86%), contrary to the allo-HCT group (42%). Of the respondents
in the SOT, allo-HCT, and auto-HCT groups, 60%, 67%, and 36%, respectively,
thought infections could be prevented with intravenous immunoglobulins (IVIg). A
majority of respondents indicated they would be interested in participating in a
randomized controlled trial evaluating the use of IVIg in the SOT and in both HCT
groups (100%, 83%, and 57%, respectively). CONCLUSIONS: Our study shows
significant variation in practice between SOT and HCT centers with respect to
screening and management of HGG. There is willingness to participate in a
randomized controlled trial to address whether Ig treatment reduces infection in
post-transplant recipients.
PMID- 28423228
TI - Targeting DNA-Dependent Protein Kinase for Cancer Therapy.
AB - The catalytic activity of DNA-dependent protein kinase (DNA-PK) is critical to
its ability to repair lethal DNA double-strand breaks (DSBs). This includes
repair of DSB lesions resulting from oxidative stress, oncogene-induced
transcription, or following therapeutic treatment of cancer cells. Armed with
this knowledge, many attempts have been made to identify small-molecule
inhibitors of DNA-PK activity as an approach to induce tumour chemo- and
radiosensitisation. This review examines the structures of known reversible and
irreversible inhibitors, including those based on chromen-4-one, arylmorpholine,
and benzaldehyde scaffolds. DNA-PK catalytic inhibitors, such as VX-984 (8-[(1S)
2-[[6-(4,6-dideuterio-2-methylpyrimidin-5-yl)pyrimidin-4-yl]amino]-1
methylethyl]quinoline-4-carboxamide) and M3814 ((S)-[2-chloro-4-fluoro-5-(7
morpholinoquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol), have now
progressed into clinical development which should help to further advance our
understanding of whether this approach is a promising therapeutic strategy for
the treatment of cancer.
PMID- 28423229
TI - Profile and outcome of first 109 cases of paediatric acute liver failure at a
specialized paediatric liver unit in India: Methodological issues.
PMID- 28423230
TI - Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity
in lung cancer cells.
AB - Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell
proliferation and oncogenesis. Here, we report that GOF p53 induces
tumorigenicity through simultaneous activation of key oncogenic pathways
including those controlling putative tumor-initiating cell functions. We
determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates
genes from multiple signaling pathways by recognizing promoters containing
distinct transcription factor (TF) binding sites. Our analytical data support a
model in which GOF p53 complexes with two TFs on the promoter-a mediator protein,
Med17, and a histone acetyl transferase, activating histone acetylation-and
enhances gene expression to signal cell proliferation and oncogenesis. Thus,
therapeutic inhibition of one GOF p53-induced pathway would be insufficient to
prevent tumor growth as the oncoprotein activates a multitude of parallel
pathways. This discovery suggests enormous selection advantage for cancer cells
with GOF p53 to induce oncogenic growth, highlighting the problems of cancer
therapy.
PMID- 28423231
TI - Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence
rate in cirrhotic patients with chronic hepatitis C.
AB - BACKGROUND AND AIMS: Arrival of direct-acting antiviral agents against hepatitis
C virus with high-sustained virological response rates and very few side effects
has drastically changed the management of hepatitis C virus infection. The impact
of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after
a first remission in patients with advanced fibrosis remains to be clarified.
METHODS: 68 consecutive hepatitis C virus patients with a first hepatocellular
carcinoma diagnosis and under remission, subsequently treated or not with a
direct-acting antiviral combination, were included. Clinical, biological and
virological data were collected at first hepatocellular carcinoma diagnosis, at
remission and during the surveillance period. RESULTS: All patients were
cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three
patients (34%) were treated with direct-acting antivirals and 96% of them
achieved sustained virological response. Median time between hepatocellular
carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR:
3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start
and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range:
3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs
4.2/100 person-months among untreated patients (P=.008). In multivariate survival
analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct
acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001).
CONCLUSIONS: Hepatocellular carcinoma recurrence rate was significantly lower
among patients treated with direct-acting antivirals compared with untreated
patients. Given the potential impact of our observation, large-scale prospective
cohort studies are needed to confirm these results.
PMID- 28423232
TI - A psychometric evaluation of the anatomy learning experiences questionnaire and
correlations with learning outcomes.
AB - The Anatomy Learning Experiences Questionnaire (ALEQ) was designed by Smith and
Mathias to explore students' perceptions and experiences of learning anatomy. In
this study, the psychometric properties of a slightly altered 34-item ALEQ (ALEQ
34) were evaluated, and correlations with learning outcomes investigated, by
surveying first- and second-year undergraduate medical students; 181 usable
responses were obtained (75% response rate). Psychometric analysis demonstrated
overall good reliability (Cronbach's alpha of 0.85). Exploratory factor analysis
yielded a 27-item, three-factor solution (ALEQ-27, Cronbach's alpha of 0.86),
described as: (Factor 1) (Reversed) challenges in learning anatomy, (Factor 2)
Applications and importance of anatomy, and (Factor 3) Learning in the dissection
laboratory. Second-year students had somewhat greater challenges and less
positive attitudes in learning anatomy than first-year students. Females reported
slightly greater challenges and less confidence in learning anatomy than males.
Total scores on summative gross anatomy examination questions correlated with
ALEQ-27, Pearson's r = 0.222 and 0.271, in years 1 and 2, respectively, and with
Factor 1, r = 0.479 and 0.317 (all statistically significant). Factor 1 also had
similar correlations across different question types (multiple choice; short
answer or essay; cadaveric; and anatomical models, bones, or radiological
images). In a retrospective analysis, Factor 1 predicted poor end-of-semester
anatomy examination results in year 1 with a sensitivity of 88% and positive
predictive value of 33%. Further development of ALEQ-27 may enable deeper
understanding of students' learning of anatomy, and its ten-item Factor 1 may be
a useful screening tool to identify at-risk students. Anat Sci Educ 10: 514-527.
(c) 2017 American Association of Anatomists.
PMID- 28423233
TI - Ivabradine vs metoprolol in patients with acute inferior wall myocardial
infarction-"Expanding arena for ivabradine".
AB - BACKGROUND: Atrioventricular (AV) blocks are of concern with the use of beta
blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart
rate with a lesser risk of AV blocks. OBJECTIVES: To compare ivabradine with
metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and
efficacy. METHODS: It was a prospective double-blind single-center randomized
controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible
patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol
(group B). Intention to treat analysis of 426 patients (group A-232 and group B
232) was performed. The primary endpoint was 30-day incidence of major adverse
cardiovascular events including death, reinfarction, complete heart block (CHB),
and heart failure. Secondary endpoints included 30 days incidence of recurrent
angina, readmission, first- or second-degree AV block, and tachyarrhythmias.
RESULTS: Both the drugs decreased the mean heart rate to 62.22+/-2.95 (group A)
vs 62.53+/-3.59 (group B) beats per minute (P=0.33). Ejection fraction improved
in both the groups (5.15+/-1.93% in group A vs 5.52+/-2.18% in group B, P=0.065).
The two groups did not differ significantly in their primary endpoints in terms
of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00),
reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00),
heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75,
P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no
significant differences in the secondary endpoints of recurrent angina,
readmission, and tachyarrhythmias except for more first- and second-degree AV
blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002).
CONCLUSIONS: Ivabradine is well tolerated and equally effective as metoprolol in
acute inferior wall ST elevation myocardial infarction patients for lowering the
heart rate with lesser risk of AV blocks.
PMID- 28423234
TI - Pulmonary vein isolation with concomitant renal artery denervation is associated
with reduction in both arterial blood pressure and atrial fibrillation burden:
Data from implantable cardiac monitor.
AB - BACKGROUND: Renal artery denervation (RDN) has provided incremental atrial
fibrillation (AF) suppression after pulmonary vein isolation (PVI) in patients
with AF in the setting of drug-resistant hypertension. OBJECTIVE: To assess the
relationship between changes of mean blood pressure (BP) and AF recurrences/AF
burden after PVI combined with RDN. METHODS: All patients from two randomized
studies with symptomatic paroxysmal AF and/or persistent AF and resistant
hypertension who underwent PVI-only (n=37) or PVI with RDN (n=39), and
implantable cardiac monitor (ICM) implantation were eligible for this study.
Mixed-effects linear models were used to investigate the effect of RDN on mean BP
and mean AF burden and associations between the two during the 12-month follow
up. RESULTS: Concomitant RDN was associated with a significant reduction in both
mean AF burden (2.43 [95% CI: 1.76-3.09] % vs 6.95 [95% CI: 5.44-8.45] %) and
mean BP (104 [95% CI: 103-106] mm Hg vs 112 [95% CI: 110-113] mm Hg). Decrease in
mean BP was positively correlated with decline in mean AF burden: reduction of 5
10 mm Hg was accompanied by a 7.0% decreased mean AF burden, with greater
reduction (up to 20 mm Hg) associated with on average 17.7% lower mean AF burden.
CONCLUSIONS: Renal artery denervation when added to PVI decreases AF recurrences,
AF burden, and mean BP. Reduction in mean BP is associated with both AF burden
and recurrences. Further large-scale studies are needed to define the mechanistic
pathway(s) of the antiarrhythmic effects of RDN.
PMID- 28423235
TI - Hepatic sinusoidal obstruction syndrome during maintenance therapy of childhood
acute lymphoblastic leukemia is associated with continuous asparaginase therapy
and mercaptopurine metabolites.
AB - BACKGROUND: Hepatic sinusoidal obstruction syndrome (SOS) during treatment of
childhood acute lymphoblastic leukemia (ALL) has mainly been associated with 6
thioguanine. The occurrence of several SOS cases after the introduction of
extended pegylated asparaginase (PEG-asparaginase) therapy in the Nordic Society
of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol led us to
hypothesize that PEG-asparaginase, combined with other drugs, may trigger SOS
during 6-thioguanine-free maintenance therapy. PROCEDURE: In children with ALL
treated in Denmark according to the NOPHO ALL2008 protocol, we investigated the
risk of SOS during methotrexate (MTX)/6-mercaptopurine (6MP) maintenance therapy
that included PEG-asparaginase until week 33 (randomized to two- vs. six-week
intervals), as well as alternating high-dose MTX or vincristine/dexamethasone
pulses every four weeks. RESULTS: Among 130 children receiving PEG-asparaginase
biweekly, 29 developed SOS (>=2 criteria: hyperbilirubinemia, hepatomegaly,
ascites, weight gain >=2.5%, unexplained thrombocytopenia <75 * 109 l-1 ) at a
median of 30 days (interquartile range [IQR]: 17-66) into maintenance (cumulative
incidence: 27%). SOS cases fulfilling one, two, or three Ponte di Legno criteria
were classified as possible (n = 2), probable (n = 8), or verified (n = 19) SOS,
respectively. Twenty-six cases (90%) occurred during PEG-asparaginase treatment,
including 21 (81%) within 14 days from the last chemotherapy pulse compared with
the subsequent 14 days (P = 0.0025). Cytotoxic 6MP metabolites were significantly
higher on PEG-asparaginase compared to after its discontinuation. Time-dependent
Cox regression analysis showed increased SOS hazard ratio (HR) for erythrocyte
levels of methylated 6MP metabolites (HR: 1.09 per 1,000 nmol/mmol hemoglobin
increase, 95% confidence interval: 1.05-1.14). Six-week PEG-asparaginase
intervals significantly reduced SOS-specific hazards (P < 0.01). CONCLUSIONS: PEG
asparaginase increases cytotoxic 6MP metabolite levels and risk of SOS,
potentially interacting with other chemotherapy pulses.
PMID- 28423236
TI - Improvement in treatment abandonment in pediatric patients with cancer in
Guatemala.
AB - BACKGROUND: Treatment refusal and abandonment are major causes of treatment
failure for children with cancer in low- and middle-income countries (LMICs),
like Guatemala. This study identified risk factors for and described the
intervention that decreased abandonment. METHODS: This was a retrospective study
of Guatemalan children (0-18 years) with cancer treated at the Unidad Nacional de
Oncologia Pediatrica (UNOP), 2001-2008, using the Pediatric Oncology Network
Database. Treatment refusal was a failure to begin treatment and treatment
abandonment was a lapse of 4 weeks or longer in treatment. The impact of medicina
integral, a multidisciplinary psychosocial intervention team at UNOP was
evaluated. Cox proportional hazards analysis identified the effect of demographic
and clinical factors on abandonment. Kaplan-Meier analysis estimated the
survival. RESULTS: Of 1,789 patients, 21% refused or abandoned treatment.
Abandonment decreased from 27% in 2001 to 7% in 2008 following the implementation
of medicina integral. Factors associated with increased risk of refusal and
abandonment: greater distance to the centre (P < 0.001), younger age (P = 0.017)
and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002)
was associated with increased risk of abandonment alone. Abandonment correlated
with decreased overall survival: 0.57 +/- 0.02 (survival +/- standard error) for
those who completed therapy versus 0.06 +/- 0.02 for those who abandoned
treatment (P < 0.001) at 8.3 years. CONCLUSION: This study identified distance,
age, year of diagnosis and indigenous race/ethnicity as risk factors for
abandonment. A multidisciplinary intervention reduced abandonment and can be
replicated in other LMICs.
PMID- 28423237
TI - Assessment of vascular response to BiOSS LIM C(r) stents vs Orsiro(r) stents in
the porcine coronary artery model.
AB - AIMS: The optimal treatment strategy for coronary bifurcation lesions is still
unknown. The aim of the study was to assess applicability of the new cobalt
chromium version of the sirolimus-eluting dedicated bifurcation BiOSS(r) LIM C
stent in comparison with regular sirolimus-eluting Orsiro(r) stent in a porcine
coronary model. METHODS: A total of 13 BiOSS(r) LIM C stents and 6 Orsiro(r)
stents were implanted in normal nonatherosclerotic porcine straight coronary
arteries of six animals using 1.2:1.0 stent-to-artery ratio. Stent geometry and
morphology were evaluated by Faxitron imaging. Vascular response was assessed by
quantitative coronary angiography (QCA), optical coherence tomography (OCT), and
histological analyses. RESULTS: OCT performed at 28 days confirmed that all
stents were patent with no signs of thrombus. In morphometric analysis, no
differences between groups regarding stent diameter (P=.141), neointima area
(P=.247), % area stenosis (P=.293), or % diameter stenosis (P=.069) were
observed. Also, no significant differences were noted between groups regarding
their histopathology scores. The injury and inflammation scores were low (mean
grade<1) in all groups. CONCLUSIONS: The novel BiOSS(r) LIM C stent demonstrates
good short-term vascular effects in a porcine coronary bifurcation model which
are comparable with Orsiro(r) stents.
PMID- 28423238
TI - Higher plasma leptin is associated with higher risk of androgenetic alopecia in
men.
AB - In addition to genetics and androgens, novel factors could play a role in
androgenetic alopecia (AGA). This study aims to investigate the association
between plasma leptin level with the risk and severity of AGA in men. Forty-eight
subjects were enrolled including 29 AGA and 19 non-AGA subjects. The plasma
leptin level was significantly higher in AGA subjects, compared to non-AGA
subjects (4.45 vs 2.76 ng/mL, P<.05). A higher plasma leptin levels were
positively correlated with the risk of developing AGA in multivariate logistic
analysis (odds ratio=2.77, P<.05). Leptin from the circulation might impact the
development of AGA.
PMID- 28423239
TI - A novel JAK inhibitor JTE-052 reduces skin inflammation and ameliorates chronic
dermatitis in rodent models: Comparison with conventional therapeutic agents.
AB - Janus kinases (JAKs) are required for several inflammatory cytokine signalling
pathways and are implicated in the pathogenesis of chronic dermatitis, including
atopic dermatitis and psoriasis. JAK inhibitors are therefore promising
therapeutic candidates for chronic dermatitis. In this study, we evaluated the
effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated
with chronic dermatitis, and compared its profile with those of conventional
therapeutic agents in rodent models of chronic dermatitis. JTE-052 inhibited the
Th1-, Th2- and Th17-type inflammatory responses of human T cells and mast cells
in vitro. Oral administration of JTE-052 inhibited skin inflammation in hapten
induced chronic dermatitis in mice, associated with reduced levels of
inflammatory cytokines in the skin and immunoglobulin (Ig) E in serum. In
contrast, although ciclosporin partly inhibited skin inflammation, it did not
reduce interleukin (IL)-4 production in skin, and enhanced IgE production in
serum. Oral administration of JTE-052 also inhibited skin inflammation in mouse
models of atopic dermatitis and psoriasis induced by a mite extract, thymic
stromal lymphopoietin or IL-23. The maximal efficacy of JTE-052 in these
dermatitis models was superior to the conventional therapeutic agents,
ciclosporin and methotrexate. Topical application of JTE-052 ointment ameliorated
hapten-induced chronic dermatitis in rats more effectively than tacrolimus
ointment. Furthermore, JTE-052 ointment did not cause the thinning of normal skin
associated with topical corticosteroids. These results indicate that JTE-052 is a
promising candidate as an anti-inflammatory drug for various types of chronic
dermatitis, with a distinctly different profile from conventional therapy
following either oral or topical application.
PMID- 28423240
TI - Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss
of N-Glycolylneuraminic Acid.
AB - About 2-3 million years ago, Alu-mediated deletion of a critical exon in the CMAH
gene became fixed in the hominin lineage ancestral to humans, possibly through a
stepwise process of selection by pathogen targeting of the CMAH product (the
sialic acid Neu5Gc), followed by reproductive isolation through female anti
Neu5Gc antibodies. Loss of CMAH has occurred independently in some other
lineages, but is functionally intact in Old World primates, including our closest
relatives, the chimpanzee. Although the biophysical and biochemical ramifications
of losing tens of millions of Neu5Gc hydroxy groups at most cell surfaces remains
poorly understood, we do know that there are multiscale effects functionally
relevant to both sides of the host-pathogen interface. Hominin CMAH loss might
also contribute to understanding human evolution, at the time when our ancestors
were starting to use stone tools, increasing their consumption of meat, and
possibly hunting. Comparisons with chimpanzees within ethical and practical
limitations have revealed some consequences of human CMAH loss, but more has been
learned by using a mouse model with a human-like Cmah inactivation. For example,
such mice can develop antibodies against Neu5Gc that could affect inflammatory
processes like cancer progression in the face of Neu5Gc metabolic incorporation
from red meats, display a hyper-reactive immune system, a human-like tendency for
delayed wound healing, late-onset hearing loss, insulin resistance,
susceptibility to muscular dystrophy pathologies, and increased sensitivity to
multiple human-adapted pathogens involving sialic acids. Further studies in such
mice could provide a model for other human-specific processes and pathologies
involving sialic acid biology that have yet to be explored.
PMID- 28423241
TI - [The reasons for the "space" of gerontology: the impact of the movements of the
Earth and Moon on the performance of the human environment].
AB - For future gerontological research specific interest are the research results
obtained at the junction of Geophysics, astronomy, and biology, and existing
links pointing to indicators of living objects with cosmophysical factors. The
paper presents data on basic astronomical factors, potentially on a regular basis
may cause gravitational effects on the biosphere as a living environment. Among
these factors are movement of the Earth and Moon described is known in astronomy
equations: the equation of the equinoxes, equation of time, as well as major
perturbations from the Sun (evection, variation and annual inequality) inferred
from the theory of lunar motion. Based on the amount of major perturbations from
the Sun, the so-called lambdaD-functions that are carried out to study the
relationship between fluctuations of the so-called "computer time", the energy of
solar radiation in the range of 605-607 nm, and the concentration of hemoglobin
and red blood cells with major perturbations from the Sun. The resulting
conclusion about the universal nature of the impact of the movements of the Moon
and the Earth on the biosphere. The tables for the period from 01.01.2015 to
31.12.2016, with the calculated values lambdaD functions that are potentially
important for analyzing their association with temporal changes of various
indicators of the body. The regularities obtained in the comparison of changes in
various biomarkers with the course of values lambdaD functions from tables, can
be predictive in the study of the functioning of humans and the biosphere for
astronomical periods. The research was carried out in Antarctica, where excluded
the influence of artificial electromagnetic fields, st. Vostok (1998-1999) and
st. Novolazarevskaya (2003-2004).
PMID- 28423242
TI - [The gravity field of the Earth: geophysical factor of gerontology (The
Vorobeichikov effect)].
AB - The results of investigations of the growth in vitro of Escherichia coli M-17,
obtained in the processing of V. M. Vorobeichikov observational data during the
movement of the scientific expedition ship "Akademik Fedorov" from St. Petersburg
to Antarctica and back, in the period from 13.11.2002 on 26.05.2003 (48th Russian
Antarctic expedition). The findings based on the growth in vitro of Escherichia
coli from changes in geographical location on a planetary scale, that doesn't
eliminate the dependence of other species of microorganisms from the spatial
position in the gravity field of the Earth. It is established that the duration
of the lag phase of Escherichia coli in the Equatorial zone close to its duration
in the high-latitude zone and Antarctic, however, the duration of the lag phase
at the equator and the Antarctic corresponds to the time of the lag phase at the
time of the Central phase of the lunar Eclipse. The conclusion about high
sensitivity in vitro of Escherichia coli to the field of gravity of the Earth,
and to syzigium events.
PMID- 28423243
TI - [Role of circadian rhythms and cellular clock in aging cancer development].
AB - Almost all the body's functions exhibit circadian rhythm maintained in a cell by
a system of Clock genes and proteins. Failure to synchronize or loss of these
rhythms are found in aged organism and are associated with risk of cancer
development. The article describes data on mechanisms of circadian rhythms
regulation in whole organism and cell, rhythm change during aging and
relationship between rhythm disturbances and tumorigenesis of different
localisations in humans and animals.
PMID- 28423244
TI - [Discontinuity of the annuity curves. II. Variability of annuity curves in
Drosophila melanogaster Canton S strain].
AB - We analyzed "five phase" structure of Drosophila melanogaster annuity curves
described earlier. It did not depend on the sample size and seemed to be stable.
We argue that: 1. there must be strict determination of "five phase" structure;
2. variability of its duration, may be induced by weak unknown signals.
PMID- 28423245
TI - [Shaotic dynamics of cardio-intervals in three age groups of indigenous and non
indigenous population of Ugra].
AB - The problem of life expectancy of indigenous and non-indigenous population of
northern territories of the Russian Federation is considered in terms of economic
growth and industrial development of the northern territories. The importance of
prolonging the period of active working age of non-indigenous population of
Khanty-Mansi Autonomous Okrug-Ugra and Yamalo-Nenets Autonomous Okrug is
increasing. Four directions for possible prolongation of the active life of non
indigenous population were presented. The problem of comparative dynamics of age
related changes of cardiovascular system on three specific age groups of female
indigenous and non-indigenous population is being considered. A decrease in
volume of quasi-attractors in the phase space of states is equivalent to
strengthening of physical activity, which is typical of normal aging. It is
proposed to use the mathematical pattern to reduce these volumes in assessing the
dynamics of human aging in the North.
PMID- 28423246
TI - [PROINFLAMMATORY CYTOKINE GENE POLYMORPHISMS AND THE PLASMA AND SYNOVIAL FLUID
LEVELS OF CYTOKINES IN PATIENTS WITH POST-TRAUMATIC KNEE OSTEOARTHRITIS].
AB - Post-traumatic knee osteoarthritis patients (n=117) and healthy people (n=94)
were investigated to determine the genotypic and allelic frequency distribution
of polymorphic loci T-31S, S+3953T IL-1beta and G-308A TNF-alpha. The plasma and
synovial fluid levels of proinflammatory cytokines IL-1beta and TNF-alpha were
measured in 31 patients. The research demonstrated that the blood and synovial
fluid levels of IL-1beta but not TNF-alpha were increased in patients with post
traumatic knee osteoarthritis. Also, the linkage between TNF-alpha level and
polymorphic locus G-308A TNF-alpha was shown: the presence of allele -308A was
associated with decreased TNF-alpha level. We demonstrated that polymorphic loci
T-31S, S+3953T IL-1beta and G-308A TNF-alpha do not predict the higher risk of
post-traumatic knee osteoarthritis development in Russian population of Rostov-on
Don region.
PMID- 28423247
TI - [COMPARATIVE MORPHOFUNCTIONAL CHARACTERISTICS OF ADULT AND OLD RAT VENTRAL
HIPPOCAMPUS TO COMBINED STRESS INFLUENCE].
AB - Animals were subjected to seven days combined stress in a special chamber (6
isolated compartments of equal area) with removable multi-modal stressors (noise,
vibration, pulsating bright light) every 5 minutes on the stochastic scheme with
restraint and temperature rise in the chamber during 30-minute stressing time
sessions. After exposure to combined stress in the ventral hippocampus of old
rats (24 months) compared with adult animals (12 months) following changes were
revealed: marked dystrophic changes and increased inducible nitric oxide synthase
expression in pyramidal neurons of CA3 field, signs of impaired hemodynamic
disorders in the microvasculature, perivascular edema, decreased endothelial
nitric oxide synthase expression in microvascular endothelial cells, as well as
decreased expression of serine racemase in the neuropil of the radial layer of
CA1 field.
PMID- 28423248
TI - [Disulfiram inhibites the development of cataract in OXYS rats].
AB - Surgical treatment remains the only way to restore vision in patients with
cataract; this disorder is the most common reason for vision decline and vision
loss in people older than 65 years. It is estimated that a 10-year delay in the
development of cataract will reduce the need for surgery twofold. In 2012, Nagai
and colleagues reported an anticataract effect of an inhibitor of acetaldehyde
dehydrogenase-a widely used antialcoholism drug disulfiram (DSF) - in ICR/f rats
with hereditary cataracts. Accordingly, the goal of the present study was to
evaluate the influence of DSF on the cataract in OXYS rats, which develop lens
alterations similar to senile cataract in humans. Instillation of DSF from age
1,5 to 3,5 months did not prevent but significantly slowed the development of
cataracts in OXYS rats. At concentrations of 0,25 % and 0,5 %, DSF reduced the
severity of pathological changes in the lens 1,8-fold and was more effective than
at the concentration 1 %. These data were consistent with the results of
ophthalmoscopic histomorphological examination: the pharmacotherapy strongly
reduced the (typical of cataract) structural damage to the capsule of the lens
epithelium and to organization of its fibers. Thus, disulfiram is a promising
drug for the prevention of senile cataract in humans.
PMID- 28423249
TI - [The investigation of blood cells of middle and old age in patients with
bronchial asthma and chronic obstructive pulmonary disease by atomic force
microscopy. Similarities and differences with the biological animal model].
AB - The investigation of reactive changes of blood cells in such diseases as COPD or
asthma in people of different age groups is the very difficult problem.
Simulating the same conditions in animals that occur in humans with these
diseases can serve as a reliable practical model. It is possible because the
changes which take places at the cellular level in animals might reflect a
similar trend in the human body.
PMID- 28423250
TI - [Association of renal function, telomere length and markers of chronic
inflammation for patients without chronic kidney and cardiovascular diseases].
AB - : Most of people over 60 years of age have decreased renal function and the
velocity of glomerular filtration rate reduction varies greatly. Presumably, one
of the probable mechanisms of accelerated decline of renal function may be a
shortening of telomere length due to chronic inflammation. The main purpose of
research was to appreciate the association of renal function, leukocytes
telomeres length and markers of chronic inflammation in patients without chronic
kidney disease and cardiovascular disease. 253 patients without chronic kidney
diseases and cardiovascular diseases were included in the study. The average age
of patients was 51,5+/-13,3 years. There were 172 women and 81 men. 55 patients
had hypertension of 1-2 degree, 46 patients had normal renal function, 207 had
mild failure of kidney function. Albuminuria was < 30 mg/day in all patients.
Multivariate linear regression analysis revealed statistically significant
correlation between albuminuria level and telomere length (p=0,023), C reactive
protein (p=0,047) and fibrinogen (p=0,001). Glomerular filtration rate, urea and
creatinine were not associated with telomere length and markers of inflammation
but were correlated well with age, p < 0,001. CONCLUSIONS: Albuminuria is mainly
associated with chronic inflammation and telomere length (from all studied
indices of renal function). Albuminuria may be regarded as a marker of
replicative cell senescence and a therapeutic target for the prevention of renal
function reduction.
PMID- 28423252
TI - [THE CHOICE OF SURGICAL TREATMENT OF OBSTRUCTIVE ILEUS IN ELDERLY AND SENILE
PATIENTS].
AB - The article presents results of treatment of 100 patients with elderly colon
cancer complicated by obstructive ileus. Patients were divided into two groups of
50 people. Main group patients for colon surgery performed using laparoscopic
techniques. The efficiency of operations on the colon laparoscopically - fewer
postoperative complications, length of postoperative hospital stay days. Deaths
in the study group was not (control - 6 %).
PMID- 28423251
TI - [ASSOCIATION OF AGE OBESITY AND METABOLIC SYNDROME IN MEN].
AB - The study included 253 men aged 22 to 74 years. Was shown that at the end of the
first period of middle age the accumulation of adipose tissue was enhanced that
was associated with the change of dominance from the gynoid to the android type
of obesity. The most pronounced increase in the frequency of occurrence of
individual components and the overall metabolic syndrome was diagnosed in men in
the second period of middle age with a following decrease in the frequency such
components as hypertriglyceridemia, low HDL cholesterol and hyperglycemia in
elderly age. In the all three age groups the value of the index of visceral
obesity was significantly higher in men with android type of obesity compared
with gynoid. Thus, the men with gynoid compared with android type of obesity have
a lower risk of development metabolic syndrome in all age groups.
PMID- 28423253
TI - [Association of renal function, telomere length and markers of chronic
inflammation for patients without chronic kidney and cardiovascular diseases].
AB - The retrospective analysis of 50 cases of acute myocardial infarction's treatment
in patients older than 90 years old was held. Patients' age ranged from 90 to 101
years old. The average age was 92,1+/-0,7 years. 20 (40 %) patients have had
reperfusion therapy: thrombolytic therapy - 2 (4 %), emergency coronary stenting
18 (36%). The mortality rate was 26 %. Mortality in groups with/without
reperfusion therapy was 20 % and 30 %, respectively. In the subgroup of coronary
stenting, 4 patients died (the mortality rate was 22,2 %). The specialized
medical care for patients over 90 years old with acute myocardial infarction
associated with high mortality (26 %). It was proved statistically that the
reduction (p < 0,05) of mortality is connected with coronary stenting. In cases
with endovascular technical possibilities' presence, even with multivessel
lesions, it is necessary to perform coronary stenting of the infarct/ischemia
responsible coronary artery. It is particularly important in cases complicated by
acute heart failure.
PMID- 28423254
TI - [Optimization of treatment of elderly patientswith diabetic foot syndrome and
mediakaltsinozom arteries].
AB - The objective of the research was to study the effectiveness of the drug
Cytoflavin in the comprehensive treatment of mixed form diabetic foot syndrome
with media calcification arteries in 75 elderly patients with type 2 diabetes.
Depending on the regimen, patients were divided into two groups: control received
basic therapy; main group in addition to the base, received the drug Cytoflavin
10 ml 0,9 % NaCl 200 ml for 10 days, followed by a transition to the tablet form
of the drug - 2 tablets 2 times per day orally for one month. The inclusion of
the drug Cytoflavin in the treatment regimen increased the effectiveness of
treatment, which was shown to improve tissue oxygenation due to the normalization
of the basal oxygen tension, restoring the activity of antioxidant enzymes and,
consequently, in an authentic decrease in the average time of hospital treatment
and a decrease in the number of repeated surgical interventions and reamputatsy
over the next year.
PMID- 28423255
TI - [AGED CARDIOHEMODYNAMICS COMPLICATED BY STROKE].
AB - A new method of arterial piezopulsometry allowed a 12-year study of the
peculiarities of age-related changes in cardiac hemodynamic indices in an aged
man after ischemic stroke. The ob-tained results enable use of these indicators
as prognostic criteria of an individual organism's re-sistance to acceleration
factors of aging, as well as its resistance to the development of the cardi
ovascular pathology caused by the stroke. Simultaneous dual registration of
piezopulsograms al-lowed establishing a significant increase of the augmentation
index of pulse pressure (AIxPP) and the velocity of the pulse wave of blood
pressure propagation through the radial artery (Var) in a paralyzed right arm,
compared to the left hand control (p < 0,05). Range fluctuations in the relative
values of this difference can serve as an objective indicator of the functional
state of a paralyzed arm of a patient during rehabilitation treatment, and a
sharp decrease of this difference and its subsequent stabilization can serve as
an indicator of the beginning of recovery.
PMID- 28423256
TI - [Cardioprotective effect of the new derivative of glutamic acid - glufimet in
acute immobilization-painful stress in animals of different ages].
AB - The effect of the 24-hour immobilization-painful stress on myocardial
contractility of young (6-month), middle-aged (12-month) and old (24-month)
female rats was studied. It was identified a reduction of the functional reserve
of the heart, which showed a smaller growth rates of contraction and relaxation
of the myocardium (+ dP/dt max and -dP/dt max), left ventricular pressure (LVP)
and the maximum intensity of the functioning of the structures (MIFS) under
increased pre- afterload and adrenergic stimulation of the heart, especially
pronounced in the group of 24-month old rats. The animals of all ages treated
before and after stressing glufimet in a dose 29 mg/kg, have higher rates of
growth + dP/dt max, -dP/dt max, LVP and MIFS during load tests, most significant
rates of growth are noticed in older rats compared with the young and middle
aged. Phenibut improves studied parameters equally at 6, 12 and 24-month old
females, subjected to stress.
PMID- 28423257
TI - [Acute myocardial infarction in elderly and senile patients: epidemiology study
according to the who program "registry of acute myocardial infarction].
AB - The article presents results of the epidemiology study of acute myocardial
infarction (AMI) among permanent Tomsk residents older than 60 years. The study
was conducted in 2008-2009 according to the WHO program "Registry of Acute
Myocardial Infarction". Data demonstrated that morbidity and mortality from AMI
was higher in the above mentioned age group than in younger population. Rates of
morbidity and mortality in men exceeded those in women in all age groups except
population older than 80 years. The study showed high in-hospital lethality
caused by high death rates in patients 60 years of age and older who were treated
in non-specialized hospitals. Authors conclude that the severity of epidemiology
situation with AMI is determined by the frequency of this pathology in population
older than 60 years suggesting the necessity of change in the strategy of system
development of medical care for AMI patients with focus on the older age groups.
PMID- 28423258
TI - [OPTIMIZATION OF REPARATIVE OSTEOGENESIS JAWS ON AGING (PRECLINICAL STUDIES)].
AB - The article presents the results of pre-clinical studies of the possibility of
optimization of reparative osteogenesis in postoperative bone cavities of the
jaws in old rats with a peptide bioregulator of Kartalaks. Using histological and
morphometric methods in the experimental study, it is shown that the use of
Kartalaks positive effect on the course of the process of reparative osteogenesis
of the mandible in old rats. The features of the Kartalaks drug investigated for
optimization of reparative osteogenesis jaw during aging. It is found that by
using Kartalaks in old animals to 30 days before the surgical intervention, the
process of reparative osteogenesis standard defect of mandible occurs at early
stages (before 30 days), similar to the control. The deadlines for 60-120 days
from the beginning of the experiment using the peptide bioregulator Kartalaks,
noted the formation of a complex regenerate tissue containing a smaller
proportion of connective tissue and cartilage, as well as more advanced
remodeling of newly formed bone tissue compared with the control group, and older
animals who received the drug after performing surgery.
PMID- 28423259
TI - [Attitudes to elderly people in everyday life: Attitudes to elderly people in
everyday life: conceptual outlines of explanation model].
AB - The article deals with problems related to the third age in contemporary Russia.
It is based on empirical data obtained in unstructured students interviews (N=53)
in Saratov and Moscow in 2007-2014. The author shows that the lack of a
respectful behavior regardless its reasons is often labeled as "disrespect". As a
result a "neutral attitude" is devoid of practical implementation. In reality a
"good attitude" to the third age is often unrealized because of the actions of
older people themselves, as these actions are incompatible with respect
practices. These asymmetrical actions are embodied in intergenerational contacts
and may take form of non-status behavior that disqualifies an elder actor as a
potential object of respect, etc.
PMID- 28423260
TI - [DIAGNOSIS OF EMOTIONAL SPHERE DISORDERS IN ELDERLY].
AB - The article describes the structure of criteria of severity and recommendations
for the diagnosis of emotional sphere disorders in elderly. An algorithm for
diagnosis of emotional sphere is described, which includes four phases: screening
and diagnostic, clinical and patho-psychological, laboratory and instrumental
diagnostic, psycho-diagnostic; it can be applied as to estimate the prevalence of
various forms of emotional disorders, and for their early correction and
prevention at the individual level. The criteria of anxiety expression evaluation
and asthenic disorders are presented. The recommendations can be used in the
activities of somatic practices doctors (therapist, general practitioners,
neurologists).
PMID- 28423261
TI - [Comparative characteristics of depressive tendencies in patients with
tuberculosis and chronic obstructive pulmonary disease].
AB - Chronic obstructive pulmonary disease (COPD) and tuberculosis are socially
significant diseases that can develop at any age, and require long-term,
sometimes lifelong, therapy. Diseases will inevitably cause a deficiency of
oxygen in the body that can cause disorders of the nervous system, from the mood
changes to reduce intelligence, especially in the elderly. According to the
results of the study the majority of patients with COPD and a third of patients
with tuberculosis, there are significant problems of the emotional plane,
especially in older and elderly expressed in the presence of depressive
tendencies (from subdepressive states to real depression), and almost half of the
patients in need of specially organized psychological or medical assistance.
PMID- 28423262
TI - [sRAGE LEVEL AND ITS ASSOCIATION WITH COGNITIVE STATUS OF PATIENTS WITH
ALZHEIMER'S DISEASE AND MIXED VASCULAR-DEGENERATIVE COGNITIVE IMPAIRMENT].
AB - The differences in level of soluble forms of receptor for advanced glycation end
products (sRAGE) in the blood serum of patients with Alzheimer's disease and
mixed vascular-degenerative cognitive impairment were studied. sRAGE in blood
serum of the patients with Alzheimer's disease is lower than that in patients
with mixed vascular-degenerative cognitive impairments. Correlation analysis of
serum sRAGE level and indicators of cognitive status was performed. Low level of
sRAGE is associated with worse memory that is typical for Alzheimer's
neurodegenerative process. This fact confirms the pathogenetic significance of
the studied biomarker.
PMID- 28423263
TI - [EXPERIENCE WITH THE USE OF EPTIFIBATIDE IN ACUTE CORONARY SYNDROME DURING
CORONARY INTERVENTION IN PATIENTS OLDER AGE GROUP].
AB - Acute coronary syndrome is the leading cause of death in patients older age
group. Primary PCI is nearly uncontested revascularization method because of its
efficacy in reperfusion achievement and less hemorrhagic complications compared
to systemic thrombolytic therapy. Nevertheless, the age of the patients is a
significant bleeding risk factor, sophisticating the choice and dosing
antiplatelet and anticoagulant therapy during coronary angioplasty and stenting.
Blocker 2b/3a receptor eptifibatide are used to avoids the development of
ischemic complications and improves myocardial perfusion, but accompanied with
bleeding risk during common infusion (12-18 hours). Combined intracoronary and
intravenous infusion eptifibatide during only coronary intervention enhance
procedure safety.
PMID- 28423264
TI - [INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH AS A MODERN
TOOL FOR ASSESSING QUALITY REHABILITATION OF PATIENTS].
AB - The article used the methods of assessment of knee function, structure and
functional activity in elderly patients with osteoarthritis to represent in terms
of the ICF structure and subsequent evaluation of the rehabilitation patient
profile and effectiveness of medical rehabilitation of patients with
osteoarthritis of the knee. It is shown that the inclusion in the program of
rehabilitation of older patients with osteoarthritis of the knee EHF-IR therapy
provides a more pronounced clinical effect. An analysis of the profile of the
rehabilitation of patients shows positive dynamics of all three components of the
assessment of the rehabilitated patients (function, structure, activity). The
data confirm the possibility of using the ICF in its use as a criterion for the
scientific evaluation of the effectiveness of rehabilitation of patients with
osteoarthritis.
PMID- 28423265
TI - [ADVANCED AND SENILE AGE FOR THE FIRST DAYS AFTER X-RAY ENDOVASCULAR
INTERVENTIONS].
AB - Research of the glomerular filtration rate at the patients of advanced and senile
age who underwent X ray endovascular intervention is conducted. Patients of age
groups are examined: 34-59 years (49,7+/-7,8 years) - 35 people (group of
control), 60-74 years (65,5+/-4,1) - 38 people and 75-82 years (77,5+/-2,5) - 12
people. Methods of screening calculation of the glomerular filtration rate are
compared. The conclusion that regardless of techniques of definition of GFR and
its initial level, the orientation of change of this parameter is characterized
by its decrease at all patients after performance of coronary angiography, but
more at patients of senile age group is drawn. It is expedient to use Cockcroft
Gault's formula for screening determination of speed of the glomerular filtration
rate at people of advanced and senile age, in particular in patients with
ischemic heart disease when carrying out X-ray endovascular interventions.
PMID- 28423266
TI - [THE DYNAMICS AND STRUCTURE OF INDICATORS OF SECONDARY DISABILITY DUE TO
CEREBROVASCULAR DISEASES IN THE ELDERLY IN ST. PETERSBURG IN THE PERIOD 2005
2014].
AB - The article presents data about secondary disability due to cerebrovascular
diseases in the elderly based on results of examination in the Bureau of medical
social expertise of Saint Petersburg in the period from 2005 to 2014. The
analysis revealed a high proportion of the disabled elderly in the structure of
disability due cerebrovascular diseases; and the growth of the share of people
with disabilities elderly in the analyzed period.
PMID- 28423267
TI - [EMPLOYMENT OF THE ELDERLY PEOPLE IN THE EUROPEAN UNION AND UKRAINE: REALITIES,
PROBLEMS AND PROSPECTS].
AB - The study focuses on the issue of older people employment in the European Union
and Ukraine. We analyzed the relationship of employment for older people and
their income, of employment and of the value of index of social capital, life
expectancy and income after retirement. It is shown that the employment rate of
older people increased even during the economic crisis. The author has outlined
the main causes of employment and the fields of activity of retirees. The basic
reasons of employment are financial motives. However, motivation does not come
from financial necessity, but because of work satisfaction in countries such as
Denmark, Austria, Sweden. The main scope of employment of retirees in Ukraine is
the industrial sector, but in the EU working retirees 65+ are engaged in
agriculture, forestry and fishing sector, self-employment widespread among
retirees. The author has outlined the basic directions of pension policy.
PMID- 28423268
TI - [ROLE alpha2-ADRENERGIC RECEPTORS IN REGULATION PLATELET REACTIVITY IN THE
ELDERLY AT CHRONIC OBSTRUCTIVE PYELONEPHRITIS].
AB - Objective of the research was to determine involvement of platelets and the role
of adrenaline in chronic inflammation maintaining and the initiation of acute
inflammatory response in elderly patients with chronic obstructive pyelonephritis
against this background. The study includes 60 patients with chronic obstructive
pyelonephritis (COPN), which are distributed into two groups: basic - 22 elderly
patients (age 73+/-1,5 years) and the comparison group - 38 middle-aged patients
(52,5+/-2,4 years). The study excluded patients who took antiplatelet drugs and
non-selective blockers of alpha adrenergic receptors at least 1 week before the
study. Analysis of platelets adrenoreactivity in vitro was carried out at the
time of hospitalization before the start of conservative therapy. Platelet-rich
plasma was isolated from peripheral blood by centrifuging. ADP and epinephrine
were used in the effective (EC50) and sub-threshold (EC10) concentrations to
stimulate platelets. The formation of platelet-leukocyte aggregates was
reproduced in vitro upon incubation of stimulated platelets (at a concentration
of adrenaline EC50) and intact leukocytes isolated from patient peripheral blood.
The study of platelet reactivity revealed that in elderly patients acute
inflammatory response realization (relapse of COPN) is against optimal
functioning of platelets alpha2 adrenergic receptors. Significant increase in the
number of platelet-leukocyte aggregates is possible. Remission of COPN (the
presence of chronic inflammation) in the examined patients of various ages was
associated with platelet hypoadrenoreactivity. Increased platelet
adrenoreactivity during transition from remission to relapse of COPN in the
elderly patients is possible if adequate synthesis of ADP in platelets and its
secretion from dense granules are preserved. The observed interaction of
adrenaline and ADP with stimulated platelet hyporesponsiveness probably ensures
adaptive response aimed at acute inflammatory response in COPN.
PMID- 28423269
TI - Sensing by Smell: Nanoparticle-Enzyme Sensors for Rapid and Sensitive Detection
of Bacteria with Olfactory Output.
AB - We present here a highly efficient sensor for bacteria that provides an olfactory
output, allowing detection without the use of instrumentation and with a modality
that does not require visual identification. The sensor platform uses
nanoparticles to reversibly complex and inhibits lipase. These complexes are
disrupted in the presence of bacteria, restoring enzyme activity and generating
scent from odorless pro-fragrance substrate molecules. This system provides rapid
(15 min) sensing and very high sensitivity (102 cfu/mL) detection of bacteria
using the human sense of smell as an output.
PMID- 28423270
TI - Bioaccumulation and Biodistribution of Selenium in Metamorphosing Tadpoles.
AB - Selenium is an important macronutrient with a very narrow margin between
essentiality and toxicity. Amphibians are hypothesized to be particularly
sensitive due to the potential for metamorphosis-driven mobilization, which could
transfer or concentrate contaminant burdens within specific organs. We explored
the potential role of tissue degeneration and remodeling during anuran
metamorphosis as a mechanism for altering tissue-specific Se burdens.
Limnodynastes peronii tadpoles were exposed to dissolved 75Se (as selenite) for 7
days and depurated until completion of metamorphosis. Bioaccumulation and
retention kinetics were assessed in whole tadpoles and excised tissues using
gamma spectroscopy, and temporal changes in biodistribution were assessed using
autoradiography. Tadpoles retained Se throughout metamorphosis, and partitioned
the element predominantly within digestive and excretory tissues, including
livers > mesonephros > guts > gallbladder. Importantly, our results demonstrate
that Se biodistribution varies significantly throughout development. This is
indicative of tissue transference, and particularly in tissues developing de novo
after depuration. To the best of our knowledge, this is the first study
demonstrating Se transference during metamorphic tissue remodelling. Further
research is warranted to explore the fate and metabolism of Se (and other metal
and metalloids) during anuran development and the implications of transference
for influencing toxicity.
PMID- 28423271
TI - Vertically Aligned Graphene Sheets Membrane for Highly Efficient Solar Thermal
Generation of Clean Water.
AB - Efficient utilization of solar energy for clean water is an attractive,
renewable, and environment friendly way to solve the long-standing water crisis.
For this task, we prepared the long-range vertically aligned graphene sheets
membrane (VA-GSM) as the highly efficient solar thermal converter for generation
of clean water. The VA-GSM was prepared by the antifreeze-assisted freezing
technique we developed, which possessed the run-through channels facilitating the
water transport, high light absorption capacity for excellent photothermal
transduction, and the extraordinary stability in rigorous conditions. As a
result, VA-GSM has achieved average water evaporation rates of 1.62 and 6.25 kg m
2 h-1 under 1 and 4 sun illumination with a superb solar thermal conversion
efficiency of up to 86.5% and 94.2%, respectively, better than that of most
carbon materials reported previously, which can efficiently produce the clean
water from seawater, common wastewater, and even concentrated acid and/or alkali
solutions.
PMID- 28423272
TI - Distinguishing Lead and Molecule States in Graphene-Based Single-Electron
Transistors.
AB - Graphene provides a two-dimensional platform for contacting individual molecules,
which enables transport spectroscopy of molecular orbital, spin, and vibrational
states. Here we report single-electron tunneling through a molecule that has been
anchored to two graphene leads. Quantum interference within the graphene leads
gives rise to an energy-dependent transmission and fluctuations in the sequential
tunnel-rates. The lead states are electrostatically tuned by a global back-gate,
resulting in a distinct pattern of varying intensity in the measured conductance
maps. This pattern could potentially obscure transport features that are
intrinsic to the molecule under investigation. Using ensemble averaged magneto
conductance measurements, lead and molecule states are disentangled, enabling
spectroscopic investigation of the single molecule.
PMID- 28423273
TI - Conformational Dynamics of Mechanically Compliant DNA Nanostructures from Coarse
Grained Molecular Dynamics Simulations.
AB - Structural DNA nanotechnology, the assembly of rigid 3D structures of complex yet
precise geometries, has recently been used to design dynamic, mechanically
compliant nanostructures with tunable equilibrium conformations and
conformational distributions. Here we use coarse-grained molecular dynamics
simulations to provide insights into the conformational dynamics of a set of
mechanically compliant DNA nanostructures-DNA hinges that use single-stranded DNA
"springs" to tune the equilibrium conformation of a layered double-stranded DNA
"joint" connecting two stiff "arms" constructed from DNA helix bundles. The
simulations reproduce the experimentally measured equilibrium angles between
hinge arms for a range of hinge designs. The hinges are found to be structurally
stable, except for some fraying of the open ends of the DNA helices comprising
the hinge arms and some loss of base-pairing interactions in the joint regions
coinciding with the crossover junctions, especially in hinges designed to exhibit
a small bending angle that exhibit large local stresses resulting in strong kinks
in their joints. Principal component analysis reveals that while the hinge
dynamics are dominated by bending motion, some twisting and sliding of hinge arms
relative to each other also exists. Forced deformation of the hinges reveals
distinct bending mechanisms for hinges with short, inextensible springs versus
those with longer, more extensible springs. Lastly, we introduce an approach for
rapidly predicting equilibrium hinge angles from individual force-deformation
behaviors of its single- and double-stranded DNA components. Taken together,
these results demonstrate that coarse-grained modeling is a promising approach
for designing, predicting, and studying the dynamics of compliant DNA
nanostructures, where conformational fluctuations become important, multiple
deformation mechanisms exist, and continuum approaches may not yield accurate
properties.
PMID- 28423274
TI - Experimental Evidence of Long-Range Intramolecular Vibrational Energy
Redistribution through Eight Covalent Bonds: NIR Irradiation Induced
Conformational Transformation of E-Glutaconic Acid.
AB - Long-range intramolecular vibrational energy redistribution (IVR) driven
conformational changes were investigated in a matrix-isolated open-chain,
asymmetrical dicarboxylic acid, E-glutaconic acid. Although the analysis was
challenging due to the presence of multiple backbone conformers and short
lifetimes of the prepared higher energy cis conformers, it was shown that the
selective excitation of the O-H stretching overtone of one of the carboxylic
groups can induce the conformational change (trans to cis) of the other
carboxylic group, located at the other end of the E-glutaconic acid molecule.
This is a direct proof that the IVR process can act through eight covalent bonds
in a flexible molecule before the excess energy completely dissipates into the
matrix. The lifetime of the prepared higher energy conformers (averaged over the
different backbones) was measured to be 12 s.
PMID- 28423275
TI - Single or Multiple Access Channels to the CYP450s Active Site? An Answer from
Free Energy Simulations of the Human Aromatase Enzyme.
AB - Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical
targets of breast and prostate anticancer therapies, critical players in drug
metabolism, and their overexpression in tumors is associated with drug
resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in
deeply buried active sites accessible only via several grueling channels, whose
exact biological role remains unclear. Gaining direct insights on the mechanism
by which ligands travel in and out is becoming increasingly important given that
channels are involved in the modulation of binding/dissociation kinetics and the
specificity of ligands toward a CYP450. This has profound implications for
enzymatic efficiency and drug efficacy/toxicity. Here, by applying free energy
methods, for a cumulative simulation time of 20 MUs, we provide detailed
atomistic characterization and free energy profiles of the entry/exit routes
preferentially followed by a substrate (androstenedione) and a last-generation
inhibitor (letrozole) to/from the catalytic site of CYP19A1 (the human aromatase
(HA) enzyme), a key clinical target against breast cancer, studied here as
prototypical CYP450. Despite the remarkably different size/shape/hydrophobicity
of the ligands, two channels appear accessible to their entrance, while only one
exit route appears to be preferential. Our study shows that the preferential
paths may be conserved among different CYP450s. Moreover, our results highlight
that, at least in the case of HA, ligand channeling is associated with large
enzyme structural rearrangements. A wise choice of the computational method and
very long simulations are, thus, required to obtain fully converged quantitative
free energy profiles, which might be used to design novel biocatalysts or next
generation cytochrome inhibitors with an in silico tuned Km.
PMID- 28423276
TI - Supramolecular beta-Sheets Stabilized Protein Nanocarriers for Drug Delivery and
Gene Transfection.
AB - Suckerin proteins, recently discovered in the sucker ring teeth of squids,
represent a family of promising structural biomacromolecules that can form
supramolecular networks stabilized by nanoconfined beta-sheets. Exploiting this
feature as well as their specific amino acid composition, we demonstrate that
artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient
drug delivery and gene transfection in vitro and in vivo. First, we demonstrate
that S-19 self-assembles into beta-sheet stabilized nanoparticles with controlled
particle sizes of 100-200 nm that are able to encapsulate hydrophobic drugs for
pH-dependent release in vitro, and that can effectively inhibit tumor growth in
vivo. We also show that S-19 can complex and stabilize plasmid DNA, with the
complexes stabilized by hydrophobic interactions of the beta-sheet domains as
opposed to electrostatic interactions commonly achieved with cationic polymers,
thus lowering cytotoxicity. The elevated Histidine content of S-19 appears
critical to trigger endosomal escape by the proton sponge effect, thereby
ensuring efficient gene transfection both in vitro and in vivo. Our study
demonstrates that S-19 represents a promising functional protein nanocarrier that
could be used for various drug and gene delivery applications.
PMID- 28423277
TI - Controlling the Intermediate Structure of an Ionic Liquid for f-Block Element
Separations.
AB - Recent research has revealed molecular structure beyond the inner coordination
sphere is essential in defining the performance of separation processes;
nevertheless, such structure remains largely unexplored. Here we apply small
angle neutron scattering (SANS) and X-ray absorption fine structure (XAFS)
spectroscopy to investigate the structure of an ionic liquid system studied for f
block element separations. SANS data reveal dramatic changes in the ionic liquid
microstructure (~150 A) which we demonstrate can be controlled by judicious
selection of counterion. Mesoscale structural features (>500 A) are also observed
as a function of metal concentration. XAFS analysis supports formation of
extended aggregate structures, similar to those observed in traditional solvent
extraction processes, and suggests additional parallels may be drawn from further
study. Achieving precise tunability over the intermediate features is an
important development in controlling mesoscale structure and realizing advanced
new forms of soft matter.
PMID- 28423278
TI - Shapes of Splattered Drops.
AB - Drops that impact and stick to a surface (splattered drops) commonly show
noncircular triple lines. Physical or chemical defects on the surface are known
to pin the triple line in this static metastable state. We report an experimental
study to relate the defect distribution on a surface to the triple-line
microstructure of such drops. Triple lines of an ensemble of splattered drops
have been imaged on a range of surfaces varying in wetting properties. Local
contact angles have been calculated, and the microscale pinning force
distribution has been estimated. We propose a novel method of estimating defect
strength distribution from the pinning forces, using extreme value analysis. From
this analysis, we show that pinning force distributions have finite upper and
lower bounds. We show that most common surfaces show both hydrophobic and
hydrophilic defects, but their strength distributions are asymmetric in relation
to the surface's advancing and receding angles. In addition, we show that the
range of microscopic pinning forces varies linearly with macroscopic contact
angle hysteresis but, surprisingly, with a nonzero intercept. We explain the
intercept by drawing an analogy to static and dynamic friction.
PMID- 28423279
TI - NgMCp+: Noble Gas Bound Half-Sandwich Complexes (Ng = He-Rn, M = Be-Ba, and Cp =
eta5-C5H5).
AB - Structures, bonding, and stability of half-sandwich complexes with general
formula, NgMCp+ (Ng = He-Rn, M = Be-Ba, Cp = eta5-C5H5) are analyzed through ab
initio computation. MCp+ complexes possess remarkable Ng binding ability,
particularly for M = Be and Mg. While for Ar-Rn bound analogues the bond
dissociation energy in the former complex ranges within 17.5-28.0 kcal mol-1, it
becomes 10.4-18.7 kcal mol-1 in the latter complex. In fact, BeCp+ is able to
form a strong bond with the two most inert elements, He and Ne. Although the Ng
binding ability of MCp+ gradually diminishes in moving from Be to Ba, the
corresponding free energy change values show that Kr-Rn bound complexes involving
the heavier congeners of Mg would remain in the bound state avoiding dissociation
into Ng and MCp+. The nature of the Ng-M bond is characterized by natural bond
orbital, electron density and energy decomposition analyses in conjunction with
the natural orbital for chemical valence (EDA-NOCV) analysis. While the electron
density analysis reveals that Ng-Be (Ng = Kr, Xe, Rn) and Ng-Mg (Ng = Xe, Rn)
bonds are partly covalent in nature, the orbital interaction (DeltaEorb) is found
to be the most important term in the Ng-M attractive energy as revealed by the
EDA-NOCV. For all Ngs, the major contribution toward the DeltaEorb energy term
originates from Ng->MCp+ sigma-donation. Additionally, CpBeNgF (Ng = Xe, Rn) and
CpNgF (Ng = Kr-Rn) are found to be viable systems with kinetic protection for the
exergonic dissociation channels, CpBeNgF -> Ng + CpBeF and CpNgF -> Ng + CpF,
respectively, where the activation free energy barrier in the latter systems
(24.1-34.7 kcal mol-1) is significantly larger than that in the former ones (6.6
8.9 kcal mol-1). CpNgF (Ng = Kr-Rn) complexes are predicted to be stable even
above 300 K, whereas CpBeNgF (Ng = Xe, Rn) would be viable up to ~100 K. While
the F-Ng bonds are ionic in nature, the Ng-Be and Ng-C bonds in these complexes
have significant covalent character.
PMID- 28423280
TI - Does a Nitrogen Lone Pair Lead to Two Centered-Three Electron (2c-3e)
Interactions in Pyridyl Radical Isomers?
AB - Each of the three isomeric pyridyl radicals (2-, 3-, and 4-dehydropyridines)
contains a lone pair and an unpaired electron. As a result, a potential two
centered-three electron interaction between the radical electron and the lone
pair through-space (TS) and/or through-bond (TB) can exist that may influence the
stability of the radicals. Due to the change in geometrical positions relative to
each other, the strength of interaction can be varied. In this study, we
investigated the structural and stability aspects of pyridyl radical isomers with
a major emphasis on the interaction of a nitrogen lone pair with the radical
center. In order to obtain evidence for such interactions, protonated and N-oxide
analogues of the corresponding isomeric pyridyl radicals have been considered in
such a way to understand the consequences due to unavailability of the lone pair.
Similarly, electron attachment and detachment energies at the radical center
(vertical detachment energy, VDE, of corresponding anions and vertical ionization
energy, VIE, of radical isomers) have been calculated to find out the interaction
trend upon modification at the radical center. Different levels of theory
including (U)B3LYP/cc-pVTZ, (U)M06/cc-pVTZ, CBS-QB3, single-point energy
calculations at (U)CCSD(T)/cc-pVTZ, and multireference CASSCF/cc-pVTZ methods
have been employed in this regard. A closer inspection of geometries, relative
stability order, spin density, electrostatic potential, molecular orbitals, NBO
analysis, and vibrational analysis have showed a strong and stabilizing TS
interaction between the radical center and the lone pair in the case of the 2
pyridyl radical. On the other hand, the 4-pyridyl radical showed stabilizing
interactions only via TB coupling, whereas the TS interaction is nonexistent.
Despite the presence of both interactions in the case of the 3-pyridyl radical,
their overall influence is less effective toward stability.
PMID- 28423281
TI - An aqueous extract from Moringa oleifera leaves ameliorates hepatotoxicity in
alloxan-induced diabetic rats.
AB - This study was carried out to evaluate the possible mechanisms through which an
aqueous extract from MO leaves demonstrates hepatoprotective effects in alloxan
induced diabetic rats. Eighty albino rats were assigned to 4 groups. The control
group was orally administered sterile saline. The second group was injected with
alloxan (150 mg/kg body mass (b.m.)) by intraperitoneal injection (i.p.). The
third group was given MO (250 mg/kg b.m.) orally, daily. The fourth group was
injected with alloxan, as for the second group, and administrated an aqueous
extract of MO leaves, as for the third group. Alloxan induced degenerative
changes in hepatic and pancreatic tissues, increased hepatic lipid peroxidation,
and increased gene expression of PC and caspase 3. However, it decreased the
activities of hepatic SOD and CAT, and gene expression of GS. In contrast, the MO
extract prevented changes to the histoarchitecture of hepatic and pancreatic
tissues and normalized the reduced hepatic levels of glutathione, as well as the
activities of SOD and CAT, and the gene expression of GS, while reducing blood
glucose levels, hepatic lipid peroxidation, and the gene expression of PC and
caspase 3. This study indicated that an aqueous extract of MO leaves can be a
potent antioxidant and used as an hepatoprotective agent.
PMID- 28423282
TI - Good Riddance to Big Insurance Mergers.
PMID- 28423283
TI - Reply: Controlled Clinical Trials and Real-Life Experience with Pulmonary
Rehabilitation.
PMID- 28423284
TI - Controlled Clinical Trials and Real-Life Experience with Pulmonary
Rehabilitation.
PMID- 28423285
TI - The Epidemiology of High Ankle Sprains in National Collegiate Athletic
Association Sports.
AB - BACKGROUND: Ankle sprains are among the most common injuries experienced by
collegiate athletes. The type of ankle sprain is rarely differentiated in
epidemiological studies. This differentiation is necessary, as each ankle sprain
type has a unique injury mechanism and recovery period. High ankle sprains
commonly result in long recovery periods. Thus, a further examination of the
epidemiology of high ankle sprains is warranted. PURPOSE: To describe the
epidemiology of high ankle sprains in National Collegiate Athletic Association
(NCAA) sports during the 2009/2010-2014/2015 academic years. STUDY DESIGN:
Descriptive epidemiology study. METHODS: NCAA Injury Surveillance Program high
ankle sprain data and athlete-exposures (AEs) from 25 sports were evaluated.
Certified athletic trainers recorded sport-related injury, event, and AE data
during team-sanctioned events. High ankle sprain injury rates per 10,000 AEs were
calculated. Percentage distributions were calculated for the amount of time lost
from sport and percentage of recurrent injuries. Injury rate ratios (RRs) and 95%
CIs compared injury rates by event type, participation restriction time, and sex.
95% CIs not containing 1.00 were considered statistically significant. RESULTS:
The overall high ankle sprain injury rate was 1.00 per 10,000 AEs. Overall, 56.7%
of high ankle sprain injuries occurred during competitions, and 9.8% of high
ankle sprain injuries were recurrent. Men's football (2.42/10,000 AEs), wrestling
(2.11/10,000 AEs), and ice hockey (1.19/10,000 AEs) had the highest high ankle
sprain injury rates. In sex-comparable sports, men had higher injury rates (RR,
1.77; 95% CI, 1.28-2.44). Player contact was the most common injury mechanism
(60.4%), and 69.0% of injuries resulted in >=1 day of participation restriction,
with 47.1% resulting in >=7 days of participation restriction and 15.8% resulting
in >21 days of participation restriction. CONCLUSION: High ankle sprains resulted
in significant participation restriction time from sport participation. The
majority of high ankle sprain injuries resulted from player contact and were
observed in contact/collision sports. The large proportion of high ankle sprains
resulting from player contact, specifically in male contact sports, is worthy of
further investigation. CLINICAL RELEVANCE: The enhanced understanding of the
epidemiology of high ankle sprains provided in our study will aid clinicians in
developing targeted injury prevention strategies to mitigate the negative
consequences of these injuries.
PMID- 28423286
TI - Protective effects of tempol in an experimental ovarian ischemia-reperfusion
injury model in female Wistar albino rats.
AB - The aim of this study was to investigate the antioxidant effects of tempol on
ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino
rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I);
Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50
mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia
group and the I/R group than in the sham group. Catalase levels were
significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and
the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower
in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50
mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30
mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group.
The levels of the histopathological parameters were significantly decreased in
the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be
used for reducing ovarian I/R injury.
PMID- 28423287
TI - Microfracture Versus Autologous Chondrocyte Implantation for Articular Cartilage
Lesions in the Knee: A Systematic Review of 5-Year Outcomes.
AB - BACKGROUND: Microfracture (MFx) and autologous chondrocyte implantation (ACI) are
2 surgical treatment options used to treat articular cartilage injuries of the
knee joint. PURPOSE: To compare the midterm to long-term clinical outcomes of MFx
versus ACI for focal chondral defects of the knee. STUDY DESIGN: Systematic
review. METHODS: A systematic review was performed by searching PubMed, the
Cochrane Library, and Embase to locate studies (level of evidence I-III)
comparing the minimum average 5-year clinical outcomes of patients undergoing MFx
versus ACI. Search terms used were "knee," "microfracture," "autologous
chondrocyte implantation," and "autologous chondrocyte transplantation." Patients
were evaluated based on treatment failure rates, magnetic resonance imaging, and
patient-reported outcome scores (Lysholm, Knee Injury and Osteoarthritis Outcome
Score [KOOS], and Tegner scores). RESULTS: Five studies (3 level I evidence, 2
level II evidence) were identified that met the inclusion criteria, including a
total of 210 patients (211 lesions) undergoing MFx and 189 patients (189 lesions)
undergoing ACI. The average follow-up among all studies was 7.0 years. Four
studies utilized first-generation, periosteum-based ACI (P-ACI), and 1 study
utilized third-generation, matrix-associated ACI (M-ACI). Treatment failure
occurred in 18.5% of patients undergoing ACI and 17.1% of patients undergoing MFx
( P = .70). Lysholm and KOOS scores were found to improve for both groups across
studies, without a significant difference in improvement between the groups. The
only significant difference in patient-reported outcome scores was found in the 1
study using M-ACI in which Tegner scores improved to a significantly greater
extent in the ACI group compared with the MFx group ( P = .003). CONCLUSION:
Patients undergoing MFx or first/third-generation ACI for articular cartilage
lesions in the knee can be expected to experience improvement in clinical
outcomes at midterm to long-term follow-up without any significant difference
between the groups.
PMID- 28423288
TI - Second Neoplasms in Patients With Hodgkin's Disease Following Combined Modality
Therapy-The Yale Experience.
AB - In the article by Koletsky et al "Second Neoplasms in Patients With Hodgkin's
Disease Following Combined Modality Therapy-The Yale Experience" (Journal of
Clinical Oncology 4:311-317, 1986), an error was made in the footnote on page 311
which described the composition of MVVPP. The corrected footnote appears below.
*MVVPP = nitrogen mustard (0.4 mg/kg on day 1 of cycle); vinblastine (6 mg/m2 on
days 22, 29, and 36); vincristine (1.4 mg/m2, 2 mg maximum dose, on days 1, 8,
and 15); procarbazine (100 mg/d on days 22 through 42); prednisone (40 mg/m2 on
days 1 through 15 for cycles 1, 3, and 5 only).
PMID- 28423289
TI - Reevaluating Eligibility Criteria - Balancing Patient Protection and
Participation in Oncology Trials.
PMID- 28423290
TI - Sickle Cell Disease.
PMID- 28423291
TI - Addressing the Opioid Epidemic - Opportunities in the Postmarketing Setting.
PMID- 28423292
TI - Case 12-2017 - A 34-Year-Old Man with Nephropathy.
PMID- 28423293
TI - Screening for Diabetic Retinopathy.
PMID- 28423294
TI - Screening for Colorectal Neoplasia.
PMID- 28423295
TI - Screening for Colorectal Neoplasia.
PMID- 28423297
TI - Osteopetrosis.
PMID- 28423296
TI - Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia.
AB - BACKGROUND: Acquired aplastic anemia results from immune-mediated destruction of
bone marrow. Immunosuppressive therapies are effective, but reduced numbers of
residual stem cells may limit their efficacy. In patients with aplastic anemia
that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin
receptor agonist, led to clinically significant increases in blood counts in
almost half the patients. We combined standard immunosuppressive therapy with
eltrombopag in previously untreated patients with severe aplastic anemia.
METHODS: We enrolled 92 consecutive patients in a prospective phase 1-2 study of
immunosuppressive therapy plus eltrombopag. The three consecutively enrolled
cohorts differed with regard to the timing of initiation and the duration of the
eltrombopag regimen (cohort 1 received eltrombopag from day 14 to 6 months,
cohort 2 from day 14 to 3 months, and cohort 3 from day 1 to 6 months). The
cohorts were analyzed separately. The primary outcome was complete hematologic
response at 6 months. Secondary end points included overall response, survival,
relapse, and clonal evolution to myeloid cancer. RESULTS: The rate of complete
response at 6 months was 33% in cohort 1, 26% in cohort 2, and 58% in cohort 3.
The overall response rates at 6 months were 80%, 87%, and 94%, respectively. The
complete and overall response rates in the combined cohorts were higher than in
our historical cohort, in which the rate of complete response was 10% and the
overall response rate was 66%. At a median follow-up of 2 years, the survival
rate was 97%; one patient died during the study from a nonhematologic cause.
Marked increases in bone marrow cellularity, CD34+ cell number, and frequency of
early hematopoietic progenitors were noted. Rates of relapse and clonal evolution
were similar to our historical experience. Severe rashes occurred in two
patients, resulting in the early discontinuation of eltrombopag. CONCLUSIONS: The
addition of eltrombopag to immunosuppressive therapy was associated with markedly
higher rates of hematologic response among patients with severe aplastic anemia
than in a historical cohort. (Funded by the National Heart, Lung, and Blood
Institute; ClinicalTrials.gov number, NCT01623167 .).
PMID- 28423298
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423299
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423300
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28423301
TI - Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis.
AB - BACKGROUND: Interleukin-23 is thought to be critical to the pathogenesis of
psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal
antibody that inhibits interleukin-23 by specifically targeting the p19 subunit
and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12
and interleukin-23 inhibitor, in patients with moderate-to-severe plaque
psoriasis. METHODS: We randomly assigned a total of 166 patients to receive
subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg
or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to
body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater
reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at
week 12. RESULTS: At week 12, the percentage of patients with a 90% or greater
reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg
and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for
ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the
PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as
compared with 18% in the ustekinumab group. Efficacy was generally maintained up
to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg
and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6
patients (15%), and 3 patients (8%), respectively, had serious adverse events,
including two basal-cell carcinomas and one major cardiovascular adverse event;
there were no serious adverse events in the 180-mg risankizumab group.
CONCLUSIONS: In this phase 2 trial, selective blockade of interleukin-23 with
risankizumab was associated with clinical responses superior to those associated
with ustekinumab. This trial was not large enough or of long enough duration to
draw conclusions about safety. (Funded by Boehringer Ingelheim;
ClinicalTrials.gov number, NCT02054481 ).
PMID- 28423302
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28423303
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28423304
TI - Candida Esophagitis.
PMID- 28423306
TI - Disclosure of newly diagnosed HIV infection and condom use at first sex after
diagnosis: a study of young Black men who have sex with men.
AB - : Background The first purpose of the present study was to determine whether
young Black men who have sex with men (YBMSM) disclose their newly diagnosed HIV
infection to a male or female partner, and to determine whether this disclosure
is related to condom use; the second was to identify correlates of disclosing
newly diagnosed HIV infection to male sex partners, including a measure of
partner-related barriers to condom use. METHODS: A sample of 125 HIV-infected
YBMSM (age 15-29 years) provided cross-sectional data used for both study
purposes. Recruitment occurred in a mid-size city in the southern US experiencing
inordinately high prevalence and incidence rates of HIV among YBMSM. Significance
was defined by an alpha level of <0.05. RESULTS: Eighty-eight YBMSM (70.4%)
indicated disclosing their newly diagnosed HIV status to the first male partner
they had sex with after being diagnosed. Of these, nine (9.1%) reported that
condoms were not used during ensuing sex with that partner. However, of the men
not disclosing, 27.0% reported not using condoms for ensuing sex (P=0.009).
Similar findings were observed relative to sex with females (P=0.057). Regarding
the second study purpose, in addition to a protective effect of advancing age,
men scoring at or above the median on a measure of partner-related barriers to
condom use were 2.4-fold more likely to not disclose compared with men scoring
below the median (P=0.04). CONCLUSION: For YBMSM, a beneficial counselling
objective relative to disclosing newly diagnosed HIV may be to help men resolve
perceptions of partner-related barriers to condom use.
PMID- 28423307
TI - Aspects of phosphorus physiology associated with phosphate-induced polar lipid
remodelling in marine microalgae.
AB - Marine microalgae exhibit a diversified phosphorus physiology and have also been
recently found to show high inter-taxa variability in their phosphate induced
polar lipids' remodelling. Identification of phosphorus physiology aspects that
are more related to lipid remodelling can contribute to better understanding of
such intricate phytoplankton lipid metabolism. Therefore, some aspects of
phosphorus physiology related to its uptake, storage and use were evaluated in a
taxonomically diversified group of nine marine microalgae that was arranged into
three subgroups, each of them including species showing similar polar lipid
responses to phosphate. Luxury phosphate uptake (PU) was the physiological aspect
best associated to microalgal polar lipid metabolism as it was maximal in species
(Picochlorum atomus, Tetraselmis suecica and Nannochloropsis gaditana) that were
able to counterbalance between phospholipids (PL) and betaine lipids (BL).
Cryptophytes (Rhodomonas baltica, Chroomonas placoidea), characterized by their
constitutive BL and flexible PL contents in response to phosphate, had almost no
luxury PU and showed higher phosphorus cell quota (QP) under phosphate
deprivation. Haptophyes (Isochrysis galbana, Diacronema vlkianum), with
constitutive BL contents and permanently minimal PL contents, showed the lowest
QP when deprived of phosphate while their luxury PU was below that for green
microalgae. Induction of alkaline phosphatase activity following phosphate
depletion was maximal in diatoms (Phaeodactylum tricornutum, Chaetoceros
gracilis) and I. galbana but it was unrelated to lipid remodelling. Despite
strong influence of taxonomy, polar lipid remodelling accounted for 38.8% of
total variation when microalgae were ordinated using their physiological
responses to phosphorus as descriptive variables.
PMID- 28423308
TI - How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life
Decrepitude.
AB - The goal of aging research is to extend healthy, active life. For decades, C.
elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have
served as a model for extended lifespan and youthfulness. However, a recent
report suggested that their longevity is associated with an undesirable
phenotype: a disproportionately long period of decrepitude at the end of life. In
the human population, such an outcome would be a burden to society, bringing into
question the relevance of daf-2 mutants as a model for life extension. However,
here we report that, following an extended period of movement, daf-2 mutants
survive longer in a decrepit state because of a beneficial trait: they are
resistant to colonization of the digestive tract by dietary bacteria, a condition
that leads to premature death in the wild-type and prevents their manifestation
of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead
both chronologically and proportionately healthier lives relative to the wild
type.
PMID- 28423309
TI - The Natural Product Cavinafungin Selectively Interferes with Zika and Dengue
Virus Replication by Inhibition of the Host Signal Peptidase.
AB - Flavivirus infections by Zika and dengue virus impose a significant global
healthcare threat with no US Food and Drug Administration (FDA)-approved
vaccination or specific antiviral treatment available. Here, we present the
discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin
is a potent and selectively active compound against Zika and all four dengue
virus serotypes. Unbiased, genome-wide genomic profiling in human cells using a
novel CRISPR/Cas9 protocol identified the endoplasmic-reticulum-localized signal
peptidase as the efficacy target of cavinafungin. Orthogonal profiling in S.
cerevisiae followed by the selection of resistant mutants pinpointed the
catalytic subunit of the signal peptidase SEC11 as the evolutionary conserved
target. Biochemical analysis confirmed a rapid block of signal sequence cleavage
of both host and viral proteins by cavinafungin. This study provides an effective
compound against the eukaryotic signal peptidase and independent confirmation of
the recently identified critical role of the signal peptidase in the replicative
cycle of flaviviruses.
PMID- 28423310
TI - c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to
Coordinate Antibody Responses.
AB - Humoral immune responses are tailored to the invading pathogen through regulation
of key transcription factors and their networks. This is critical to establishing
effective antibody-mediated responses, yet it is unknown how B cells integrate
pathogen-induced signals to drive or suppress transcriptional programs
specialized for each class of pathogen. Here, we detail the key role of the
transcription factor c-Myb in regulating the T-bet-mediated anti-viral program.
Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3
expression by upregulating T-bet, normally suppressed during Th2-cell-mediated
responses. Enhanced expression of T-bet resulted in aberrant plasma cell
differentiation within the germinal center, mediated by CXCR3 expression. These
findings identify a dual role for c-Myb in limiting inappropriate effector
responses while coordinating plasma cell differentiation with germinal center
egress. Identifying such intrinsic regulators of specialized antibody responses
can assist in vaccine design and therapeutic intervention in B-cell-mediated
immune disorders.
PMID- 28423311
TI - Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult
Mammalian Carotid Body.
AB - Adult stem cell plasticity, or the ability of somatic stem cells to cross
boundaries and differentiate into unrelated cell types, has been a matter of
debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a
remarkable plasticity during development. Whether adult populations of NCSCs
retain this plasticity is largely unknown. Herein, we describe that neural-crest
derived adult carotid body stem cells (CBSCs) are able to undergo endothelial
differentiation in addition to their reported role in neurogenesis, contributing
to both neurogenic and angiogenic processes taking place in the organ during
acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is
hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released
vascular cytokines such as erythropoietin. Our data highlight a remarkable
physiological plasticity in an adult population of tissue-specific stem cells and
could have impact on the use of these cells for cell therapy.
PMID- 28423312
TI - HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem
Cells into GAlert.
AB - The activation of quiescent stem cells into the cell cycle is a key step in
initiating the process of tissue repair. We recently reported that quiescent stem
cells can transition into GAlert, a cellular state in which they have an
increased functional ability to activate and participate in tissue repair.
However, the precise molecular signals that induce GAlert in stem cells have
remained elusive. Here, we show that the injury-induced regulation of hepatocyte
growth factor (HGF) proteolytic processing via the systemic protease, hepatocyte
growth factor activator (HGFA), stimulates GAlert in skeletal muscle stem cells
(MuSCs) and fibro-adipogenic progenitors (FAPs). We demonstrate that
administering active HGFA to animals is sufficient to induce GAlert in stem cells
throughout the body and to significantly accelerate the processes of stem cell
activation and tissue repair. Our data suggest that factors that induce GAlert
will have broad therapeutic applications for regenerative medicine and wound
healing.
PMID- 28423314
TI - Cyanobacteria Maintain Constant Protein Concentration despite Genome Copy-Number
Variation.
AB - The cyanobacterium Synechococcus elongatus PCC 7942 has multiple copies of its
single chromosome, and the copy number varies in individual cells, providing an
ideal system to study the effect of genome copy-number variation on cell size and
gene expression. Using single-cell fluorescence imaging, we found that protein
concentration remained constant across individual cells regardless of genome copy
number. Cell volume and the total protein amount from a single gene were both
positively, linearly correlated with genome copy number, suggesting that changes
in cell volume play an important role in buffering genome copy-number variance.
This study provides a quantitative examination of gene expression regulation in
cells with variable genome copies and sheds light on the compensation mechanisms
for variance in genome copy number.
PMID- 28423305
TI - Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes.
AB - BACKGROUND: In patients who have had type 1 diabetes for 5 years, current
recommendations regarding screening for diabetic retinopathy include annual
dilated retinal examinations to detect proliferative retinopathy or clinically
significant macular edema, both of which require timely intervention to preserve
vision. During 30 years of the Diabetes Control and Complications Trial (DCCT)
and its longitudinal follow-up Epidemiology of Diabetes Interventions and
Complications (EDIC) study, retinal photography was performed at intervals of 6
months to 4 years. METHODS: We used retinal photographs from the DCCT/EDIC study
to develop a rational screening frequency for retinopathy. Markov modeling was
used to determine the likelihood of progression to proliferative diabetic
retinopathy or clinically significant macular edema in patients with various
initial retinopathy levels (no retinopathy or mild, moderate, or severe
nonproliferative diabetic retinopathy). The models included recognized risk
factors for progression of retinopathy. RESULTS: Overall, the probability of
progression to proliferative diabetic retinopathy or clinically significant
macular edema was limited to approximately 5% between retinal screening
examinations at 4 years among patients who had no retinopathy, 3 years among
those with mild retinopathy, 6 months among those with moderate retinopathy, and
3 months among those with severe nonproliferative diabetic retinopathy. The risk
of progression was also closely related to mean glycated hemoglobin levels. The
risk of progression from no retinopathy to proliferative diabetic retinopathy or
clinically significant macular edema was 1.0% over 5 years among patients with a
glycated hemoglobin level of 6%, as compared with 4.3% over 3 years among
patients with a glycated hemoglobin level of 10%. Over a 20-year period, the
frequency of eye examinations was 58% lower with our practical, evidence-based
schedule than with routine annual examinations, which resulted in substantial
cost savings. CONCLUSIONS: Our model for establishing an individualized schedule
for retinopathy screening on the basis of the patient's current state of
retinopathy and glycated hemoglobin level reduced the frequency of eye
examinations without delaying the diagnosis of clinically significant disease.
(Funded by the National Institute of Diabetes and Digestive and Kidney Diseases
and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360893 and NCT00360815 .).
PMID- 28423313
TI - Power Grid Protection of the Muscle Mitochondrial Reticulum.
AB - Mitochondrial network connectivity enables rapid communication and distribution
of potential energy throughout the cell. However, this connectivity puts the
energy conversion system at risk, because damaged elements could jeopardize the
entire network. Here, we demonstrate the mechanisms for mitochondrial network
protection in heart and skeletal muscle (SKM). We find that the cardiac
mitochondrial reticulum is segmented into subnetworks comprising many
mitochondria linked through abundant contact sites at highly specific
intermitochondrial junctions (IMJs). In both cardiac and SKM subnetworks, a rapid
electrical and physical separation of malfunctioning mitochondria occurs,
consistent with detachment of IMJs and retraction of elongated mitochondria into
condensed structures. Regional mitochondrial subnetworks limit the cellular
impact of local dysfunction while the dynamic disconnection of damaged
mitochondria allows the remaining mitochondria to resume normal function within
seconds. Thus, mitochondrial network security is comprised of both proactive and
reactive mechanisms in striated muscle cells.
PMID- 28423315
TI - miR-132/212 Modulates Seasonal Adaptation and Dendritic Morphology of the Central
Circadian Clock.
AB - The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day
length information by mechanisms that are not well understood. Here, we report
that genetic ablation of miR-132/212 alters entrainment to different day lengths
and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2
expression in the SCN. SCN neurons from miR-132/212-deficient mice have
significantly reduced dendritic spine density, along with altered methyl CpG
binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day
length regulates spine density on SCN neurons in a melatonin-independent manner,
as well as expression of miR-132, miR-212, and their direct target, MeCP2.
Genetic disruption of Mecp2 fully restores the level of dendritic spines of miR
132/212-deficient SCN neurons. Our results reveal that, by regulating the
dendritic structure of SCN neurons through a MeCP2-dependent mechanism, miR
132/212 affects the capacity of the SCN to encode seasonal time.
PMID- 28423316
TI - Diversity in Excitation-Inhibition Mismatch Underlies Local Functional
Heterogeneity in the Rat Auditory Cortex.
AB - Cortical neurons are heterogeneous in their functional properties. This
heterogeneity is fundamental for the processing of different features of sensory
information. However, functional diversity within a local group of neurons is
poorly understood. Here, we demonstrate that neighboring cortical neurons in
layer 5 but not those of layer 4 of the rat anterior auditory field (AAF)
exhibited a surprisingly high level of diversity in tonal receptive fields. In
vivo whole-cell voltage-clamp recordings revealed that the diversity of frequency
representation was due to a spectral mismatch between synaptic excitation and
inhibition to varying degrees. The spectral distribution of excitation was skewed
at different levels, whereas inhibition was homogeneous and non-skewed, similar
to the summed spiking activity of local neuronal ensembles, which further
enhanced diversity. Our results indicate that AAF in the auditory cortex is
involved in processing auditory information in a highly refined manner that is
important for complex pattern recognition.
PMID- 28423317
TI - Loss of Navbeta4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons
Disrupts Firing and Impairs Motor Coordination and Balance.
AB - The resurgent component of voltage-gated Na+ (Nav) currents, INaR, has been
suggested to provide the depolarizing drive for high-frequency firing and to be
generated by voltage-dependent Nav channel block (at depolarized potentials) and
unblock (at hyperpolarized potentials) by the accessory Navbeta4 subunit. To test
these hypotheses, we examined the effects of the targeted deletion of Scn4b
(Navbeta4) on INaR and on repetitive firing in cerebellar Purkinje neurons. We
show here that Scn4b-/- animals have deficits in motor coordination and balance
and that firing rates in Scn4b-/- Purkinje neurons are markedly attenuated.
Acute, in vivo short hairpin RNA (shRNA)-mediated "knockdown" of Navbeta4 in
adult Purkinje neurons also reduced spontaneous and evoked firing rates. Dynamic
clamp-mediated addition of INaR partially rescued firing in Scn4b-/- Purkinje
neurons. Voltage-clamp experiments revealed that INaR was reduced (by ~50%), but
not eliminated, in Scn4b-/- Purkinje neurons, revealing that additional
mechanisms contribute to generation of INaR.
PMID- 28423318
TI - Oligodendrocyte Nf1 Controls Aberrant Notch Activation and Regulates Myelin
Structure and Behavior.
AB - The RASopathy neurofibromatosis type 1 (NF1) is one of the most common autosomal
dominant genetic disorders. In NF1 patients, neurological issues may result from
damaged myelin, and mice with a neurofibromin gene (Nf1) mutation show white
matter (WM) defects including myelin decompaction. Using mouse genetics, we find
that altered Nf1 gene-dose in mature oligodendrocytes results in progressive
myelin defects and behavioral abnormalities mediated by aberrant Notch
activation. Blocking Notch, upstream mitogen-activated protein kinase (MAPK), or
nitric oxide signaling rescues myelin defects in hemizygous Nf1 mutants, and
pharmacological gamma secretase inhibition rescues aberrant behavior with no
effects in wild-type (WT) mice. Concomitant pathway inhibition rescues myelin
abnormalities in homozygous mutants. Notch activation is also observed in Nf1+/-
mouse brains, and cells containing active Notch are increased in NF1 patient WM.
We thus identify Notch as an Nf1 effector regulating myelin structure and
behavior in a RASopathy and suggest that inhibition of Notch signaling may be a
therapeutic strategy for NF1.
PMID- 28423319
TI - TAM Receptors Are Not Required for Zika Virus Infection in Mice.
AB - Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection
with the Zika virus (ZIKV), an emerging flavivirus of global public health
concern. To investigate the requirement of TAM receptors for ZIKV infection, we
used several routes of viral inoculation and compared viral replication in wild
type versus Axl-/-, Mertk-/-, Axl-/-Mertk-/-, and Axl-/-Tyro3-/- mice in various
organs. Pregnant and non-pregnant mice treated with interferon-alpha-receptor
(IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed
no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody,
adult female mice challenged intravaginally with ZIKV showed no difference in
mucosal viral titers. Similarly, in young mice that were infected with ZIKV
intracranially or intraperitoneally, ZIKV replication occurred in the absence of
TAM receptors, and no differences in cell tropism were observed. These findings
indicate that, in mice, TAM receptors are not required for ZIKV entry and
infection.
PMID- 28423320
TI - Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+
TCR Repertoires to Immunodominant Viral Antigens.
AB - A diverse T cell receptor (TCR) repertoire is essential for controlling viral
infections. However, information about TCR repertoires to defined viral antigens
is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two
dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL)
of influenza A virus. The highly individualized repertoires (87-5,533 alpha or
beta clonotypes per subject) comprised thousands of unique TCRalpha and TCRbeta
sequences and dozens of distinct complementary determining region (CDR)3alpha and
CDR3beta motifs. However, diversity is effectively restricted by preferential V-J
combinations, CDR3 lengths, and CDR3alpha/CDR3beta pairings. Structures of two
GIL-specific TCRs bound to GIL-HLA-A2 provided a potential explanation for the
lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral
TCRs occupied up to 3.4% of the CD8+ TCRbeta repertoire, ensuring broad T cell
responses to single epitopes. Our portrait of two anti-viral TCR repertoires may
inform the development of predictors of immune protection.
PMID- 28423321
TI - Hepatocellular Carcinomas Originate Predominantly from Hepatocytes and Benign
Lesions from Hepatic Progenitor Cells.
AB - Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However,
its origin remains a debated question. Using human data and various
hepatocarcinogenesis mouse models, we show that, in early stages, transformed
hepatocytes, independent of their proliferation status, activate hepatic
progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes
reveals that, in all models, HCC originates from hepatocytes. However, whereas in
various models tumors do not emanate from HPCs, tracking of progenitors in a
model mimicking human hepatocarcinogenesis indicates that HPCs can generate
benign lesions (regenerative nodules and adenomas) and aggressive HCCs.
Mechanistically, galectin-3 and alpha-ketoglutarate paracrine signals emanating
from oncogene-expressing hepatocytes instruct HPCs toward HCCs. alpha
Ketoglutarate preserves an HPC undifferentiated state, and galectin-3 maintains
HPC stemness, expansion, and aggressiveness. Pharmacological or genetic blockage
of galectin-3 reduces HCC, and its expression in human HCC correlates with poor
survival. Our findings may have clinical implications for liver regeneration and
HCC therapy.
PMID- 28423322
TI - Intratumoral Cancer Cell Intravasation Can Occur Independent of Invasion into the
Adjacent Stroma.
AB - Intravasation, active entry of cancer cells into the circulation, is often
considered to be a relatively late event in tumor development occurring after
stromal invasion. Here, we provide evidence that intravasation can be initiated
early during tumor development and proceed in parallel to or independent of tumor
invasion into surrounding stroma. By applying direct and unbiased intravasation
scoring methods to two histologically distinct human cancer types in live-animal
models, we demonstrate that intravasation takes place almost exclusively within
the tumor core, involves intratumoral vasculature, and does not involve
vasculotropic cancer cells invading tumor-adjacent stroma and migrating along
tumor-converging blood vessels. Highlighting an additional role for EGFR in
cancer, we find that EGFR is required for the development of an intravasation
sustaining intratumoral vasculature. Intratumoral localization of intravasation
supports the notion that overt metastases in cancer patients could be initiated
much earlier during cancer progression than appreciated within conventional
clinical tumor staging systems.
PMID- 28423323
TI - Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation
to Preferentially Phosphorylate Membrane Substrates.
AB - Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular
localization of PKA is controlled by A-kinase anchoring proteins (AKAPs).
However, the dynamics of PKA upon activation remain poorly understood. Here, we
report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a
significant percentage of the PKA catalytic subunit (PKA-C) molecules to be
released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated
with the membrane via N-terminal myristoylation. This membrane association does
not require the interaction between PKA-R and AKAPs. It slows the mobility of PKA
C and enriches kinase activity on the membrane. Membrane-residing PKA substrates
are preferentially phosphorylated compared to cytosolic substrates. Finally, the
myristoylation of PKA-C is critical for normal synaptic function and plasticity.
We propose that activation-dependent association of PKA-C renders the membrane a
unique PKA-signaling compartment. Constrained mobility of PKA-C may synergize
with AKAP anchoring to determine specific PKA function in neurons.
PMID- 28423325
TI - Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription,
Splicing, and Translation Events during T Cell Responses.
AB - Activation of immune cells results in rapid functional changes, but how such fast
changes are accomplished remains enigmatic. By combining time courses of 4sU-seq,
RNA-seq, ribosome profiling (RP), and RNA polymerase II (RNA Pol II) ChIP-seq
during T cell activation, we illustrate genome-wide temporal dynamics for ~10,000
genes. This approach reveals not only immediate-early and posttranscriptionally
regulated genes but also coupled changes in transcription and translation for
>90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily
mediates transcriptional changes. This coincides with a genome-wide temporary
slowdown in cotranscriptional splicing, even for polyadenylated mRNAs that are
localized at the chromatin. Subsequent splicing optimization correlates with
increasing Ser-2 phosphorylation of the RNA Pol II carboxy-terminal domain (CTD)
and activation of the positive transcription elongation factor (pTEFb). Thus,
rapid de novo recruitment of RNA Pol II dictates the course of events during T
cell activation, particularly transcription, splicing, and consequently
translation.
PMID- 28423324
TI - Resolving Subcellular miRNA Trafficking and Turnover at Single-Molecule
Resolution.
AB - Regulation of microRNA (miRNA) localization and stability is critical for their
extensive cytoplasmic RNA silencing activity and emerging nuclear functions.
Here, we have developed single-molecule fluorescence-based tools to assess the
subcellular trafficking, integrity, and activity of miRNAs. We find that seed
matched RNA targets protect miRNAs against degradation and enhance their nuclear
retention. While target-stabilized, functional, cytoplasmic miRNAs reside in high
molecular-weight complexes, nuclear miRNAs, as well as cytoplasmic miRNAs
targeted by complementary anti-miRNAs, are sequestered stably within
significantly lower-molecular-weight complexes and rendered repression
incompetent. miRNA stability and activity depend on Argonaute protein abundance,
whereas miRNA strand selection, unwinding, and nuclear retention depend on
Argonaute identity. Taken together, our results show that miRNA degradation
competes with Argonaute loading and target binding to control subcellular miRNA
abundance for gene silencing surveillance. Probing single cells for miRNA
activity, trafficking, and metabolism promises to facilitate screening for
effective miRNA mimics and anti-miRNA drugs.
PMID- 28423327
TI - Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression
Level.
PMID- 28423326
TI - Rapid Molecular Profiling of Defined Cell Types Using Viral TRAP.
AB - Translational profiling methodologies enable the systematic characterization of
cell types in complex tissues, such as the mammalian brain, where neuronal
isolation is exceptionally difficult. Here, we report a versatile strategy for
profiling CNS cell types in a spatiotemporally restricted fashion by engineering
a Cre-dependent adeno-associated virus expressing an EGFP-tagged ribosomal
protein (AAV-FLEX-EGFPL10a) to access translating mRNAs by translating ribosome
affinity purification (TRAP). We demonstrate the utility of this AAV to target a
variety of genetically and anatomically defined neural populations expressing Cre
recombinase and illustrate the ability of this viral TRAP (vTRAP) approach to
recapitulate the molecular profiles obtained by bacTRAP in corticothalamic
neurons across multiple serotypes. Furthermore, spatially restricting adeno
associated virus (AAV) injections enabled the elucidation of regional differences
in gene expression within this cell type. Altogether, these results establish the
broad applicability of the vTRAP strategy for the molecular dissection of any CNS
or peripheral cell type that can be engineered to express Cre.
PMID- 28423329
TI - The Dynamic Cytokine Niche.
AB - Immune cells communicate using cytokine signals, but the quantitative rules of
this communication aren't clear. In this issue of Immunity, Oyler-Yaniv et al.
(2017) suggest that the distribution of a cytokine within a lymphatic organ is
primarily governed by the local density of cells consuming it.
PMID- 28423328
TI - Treating Flu with Skin of Frog.
AB - Glands in frog skin secrete substances that possess broad antimicrobial function.
Holthausen et al. mined this soup of natural products and discovered a peptide
that destroys diverse human influenza strains (Holthausen et al., 2017). This
study points the way to the discovery of novel anti-influenza molecules targeting
conserved elements on influenza surface proteins.
PMID- 28423330
TI - The Birds, the Bees, and Innate Immunity.
AB - The cytoplasm is usually a DNA-free zone, but during fertilization, sperm DNA
enters oocyte cytoplasm and could potentially trigger a response. Abe et al.
(2017) identify NLRP14 as a germ-cell-specific negative regulator of DNA sensing
that may be of particular importance during fertilization.
PMID- 28423331
TI - Cell-Intrinsic Defense at the Epithelial Border Wall: Salmonella Pays the Price.
AB - Within the gut, Salmonella-infected enterocytes are expelled into the lumen,
limiting pathogen replication. In this issue of Immunity, Rauch et al. (2017)
expand our understanding of this cell-intrinsic response by characterizing the
genetic determinants that control the expulsion and death of epithelial cells.
PMID- 28423332
TI - Caught in the cROSsfire: GSH Controls T Cell Metabolic Reprogramming.
AB - T cell activation and proliferation critical for protective immunity depend on
appropriate rewiring of cellular metabolism. In this issue of Immunity, Mak et
al. (2017) show that the antioxidant gluthathione (GSH) controls reactive oxygen
species (ROS)-dependent engagement of metabolic signaling pathways that lead to
protective T cell responses.
PMID- 28423333
TI - Hunting Down the HIV-1 Reservoir: A Starring Role for Antibodies?
AB - The persistence of viruses "hidden" in a reservoir of latently infected CD4+ T
cells under antiretroviral therapy is the major obstacle to an HIV-1 cure.
Recently published in Nature, two seminal studies from Descours et al. (2017) and
Nishimura et al. (2017) bring hope for tracking and possibly eradicating the HIV
1 reservoir.
PMID- 28423334
TI - Two Strings in One Bow: PD-1 Negatively Regulates via Co-receptor CD28 on T
Cells.
AB - The identity of PD-1 dependency on other receptors and signaling has been
unclear. In a recent issue of Science, Hui et al. (2017) and Kamphorst et al.
(2017) now show that CD28 expression is a target of PD-1-associated phosphatases
and is needed for T cell expansion in anti-PD-1 immunotherapy.
PMID- 28423335
TI - Regionalized Development and Maintenance of the Intestinal Adaptive Immune
Landscape.
AB - The intestinal immune system has the daunting task of protecting us from
pathogenic insults while limiting inflammatory responses against the resident
commensal microbiota and providing tolerance to food antigens. This role is
particularly impressive when one considers the vast mucosal surface and changing
landscape that the intestinal immune system must monitor. In this review, we
highlight regional differences in the development and composition of the adaptive
immune landscape of the intestine and the impact of local intrinsic and
environmental factors that shape this process. To conclude, we review the
evidence for a critical window of opportunity for early-life exposures that
affect immune development and alter disease susceptibility later in life.
PMID- 28423336
TI - Lung Homeostasis: Influence of Age, Microbes, and the Immune System.
AB - Pulmonary immune homeostasis is maintained by a network of tissue-resident cells
that continually monitor the external environment, and in health, instruct
tolerance to innocuous inhaled particles while ensuring that efficient and rapid
immune responses can be mounted against invading pathogens. Here we review the
multiple pathways that underlie effective lung immunity in health, and discuss
how these may be affected by external environmental factors and contribute to
chronic inflammation during disease. In this context, we examine the current
understanding of the impact of the microbiota in immune development and function
and in the setting of the threshold for immune responses that maintains the
balance between tolerance and chronic inflammation in the lung. We propose that
host interactions with microbes are critical for establishing the immune
landscape of the lungs.
PMID- 28423338
TI - An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing
Influenza Viruses.
AB - Although vaccines confer protection against influenza A viruses, antiviral
treatment becomes the first line of defense during pandemics because there is
insufficient time to produce vaccines. Current antiviral drugs are susceptible to
drug resistance, and developing new antivirals is essential. We studied host
defense peptides from the skin of the South Indian frog and demonstrated that one
of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing
human influenza A viruses. This peptide specifically targeted the conserved stalk
region of H1 hemagglutinin and was effective against drug-resistant H1 influenza
viruses. Using electron microscopy, we showed that this peptide physically
destroyed influenza virions. It also protected naive mice from lethal influenza
infection. Urumin represents a unique class of anti-influenza virucide that
specifically targets the hemagglutinin stalk region, similar to targeting of
antibodies induced by universal influenza vaccines. Urumin therefore has the
potential to contribute to first-line anti-viral treatments during influenza
outbreaks.
PMID- 28423337
TI - Homeostatic Immunity and the Microbiota.
AB - The microbiota plays a fundamental role in the induction, education, and function
of the host immune system. In return, the host immune system has evolved multiple
means by which to maintain its symbiotic relationship with the microbiota. The
maintenance of this dialogue allows the induction of protective responses to
pathogens and the utilization of regulatory pathways involved in the sustained
tolerance to innocuous antigens. The ability of microbes to set the immunological
tone of tissues, both locally and systemically, requires tonic sensing of
microbes and complex feedback loops between innate and adaptive components of the
immune system. Here we review the dominant cellular mediators of these
interactions and discuss emerging themes associated with our current
understanding of the homeostatic immunological dialogue between the host and its
microbiota.
PMID- 28423339
TI - Germ-Cell-Specific Inflammasome Component NLRP14 Negatively Regulates Cytosolic
Nucleic Acid Sensing to Promote Fertilization.
AB - Cytosolic sensing of nucleic acids initiates tightly regulated programs to limit
infection. Oocyte fertilization represents a scenario wherein inappropriate
responses to exogenous yet non-pathogen-derived nucleic acids would have negative
consequences. We hypothesized that germ cells express negative regulators of
nucleic acid sensing (NAS) in steady state and applied an integrated data-mining
and functional genomics approach to identify a rheostat of DNA and RNA sensing
the inflammasome component NLRP14. We demonstrated that NLRP14 interacted
physically with the nucleic acid sensing pathway and targeted TBK1 (TANK binding
kinase 1) for ubiquitination and degradation. We further mapped domains in NLRP14
and TBK1 that mediated the inhibitory function. Finally, we identified a human
nonsense germline variant associated with male sterility that results in loss of
NLRP14 function and hyper-responsiveness to nucleic acids. The discovery points
to a mechanism of nucleic acid sensing regulation that may be of particular
importance in fertilization.
PMID- 28423340
TI - Transforming Growth Factor-beta Signaling in Regulatory T Cells Controls T Helper
17 Cells and Tissue-Specific Immune Responses.
AB - Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue
environments and against many inflammatory insults, yet the tissue-enriched
factor(s) that influence Treg cell phenotype and function remain largely unknown.
We have shown a vital role for transforming growth factor-beta (TGF-beta) signals
in safe-guarding specific Treg cell functions. TGF-beta signals were dispensable
for steady-state Treg cell homeostasis and for Treg cell suppression of T cell
proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells
require TGF-beta signals to appropriately dampen Th17 cells and regulate
responses in the gastrointestinal tract. TGF-beta signaling maintains CD103
expression, promotes expression of the colon-specific trafficking molecule GPR15,
and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg
cells, collectively supporting the accumulation and retention of Treg cells in
the colon and control of colitogenic responses. Thus, we reveal an unrecognized
function for TGF-beta signaling as an upstream factor controlling Treg cell
activity in specific tissue environments.
PMID- 28423341
TI - Glutathione Primes T Cell Metabolism for Inflammation.
AB - Activated T cells produce reactive oxygen species (ROS), which trigger the
antioxidative glutathione (GSH) response necessary to buffer rising ROS and
prevent cellular damage. We report that GSH is essential for T cell effector
functions through its regulation of metabolic activity. Conditional gene
targeting of the catalytic subunit of glutamate cysteine ligase (Gclc) blocked
GSH production specifically in murine T cells. Gclc-deficient T cells initially
underwent normal activation but could not meet their increased energy and
biosynthetic requirements. GSH deficiency compromised the activation of mammalian
target of rapamycin-1 (mTOR) and expression of NFAT and Myc transcription
factors, abrogating the energy utilization and Myc-dependent metabolic
reprogramming that allows activated T cells to switch to glycolysis and
glutaminolysis. In vivo, T-cell-specific ablation of murine Gclc prevented
autoimmune disease but blocked antiviral defense. The antioxidative GSH pathway
thus plays an unexpected role in metabolic integration and reprogramming during
inflammatory T cell responses.
PMID- 28423343
TI - Chitosan as coagulant on cyanobacteria in lake restoration management may cause
rapid cell lysis.
AB - Combining coagulant and ballast to remove cyanobacteria from the water column is
a promising restoration technique to mitigate cyanobacterial nuisance in surface
waters. The organic, biodegradable polymer chitosan has been promoted as a
coagulant and is viewed as non-toxic. In this study, we show that chitosan may
rapidly compromise membrane integrity and kill certain cyanobacteria leading to
release of cell contents in the water. A strain of Cylindrospermopsis raciborskii
and one strain of Planktothrix agardhii were most sensitive. A 1.3 h exposure to
a low dose of 0.5 mg l-1 chitosan already almost completely killed these cultures
resulting in release of cell contents. After 24 h, reductions in PSII
efficiencies of all cyanobacteria tested were observed. EC50 values varied from
around 0.5 mg l-1 chitosan for the two sensitive strains, via about 5 mg l-1
chitosan for an Aphanizomenon flos-aquae strain, a toxic P. agardhii strain and
two Anabaena cylindrica cultures, to more than 8 mg l-1 chitosan for a
Microcystis aeruginosa strain and another A. flos-aquae strain. Differences in
sensitivity to chitosan might be related to polymeric substances that surround
cyanobacteria. Rapid lysis of toxic strains is likely and when chitosan flocking
and sinking of cyanobacteria is considered in lake restoration, flocculation
efficacy studies should be complemented with investigation on the effects of
chitosan on the cyanobacteria assemblage being targeted.
PMID- 28423342
TI - A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via
a Long, Rigidified, and Anionic beta-Hairpin Structure.
AB - Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are
prophylactic and therapeutic agents. Some of the most potent bnAbs target a
quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using
cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145,
in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated
between glycans at the trimer 3-fold axis, to contact peptide residues from all
three Env protomers, and thus explains its highly trimer-specific nature. Somatic
hypermutation in the other CDRs of PGT145 were crucially involved in stabilizing
the structure of the HCDR3, similar to bovine antibodies, to aid in recognition
of a cluster of conserved basic residues hypothesized to facilitate trimer
disassembly during viral entry. Overall, the findings exemplify the creative
solutions that the human immune system can evolve to recognize a conserved motif
buried under a canopy of glycans.
PMID- 28423344
TI - Prolonged dark period modulates the oxidative burst and enzymatic antioxidant
systems in the leaves of salicylic acid-treated tomato.
AB - Salicylic acid (SA) is an important plant growth regulator playing a role in the
hypersensitive reaction (HR) and the induction of systemic acquired resistance.
Since the SA-mediated signalling pathways and the formation of reactive oxygen
species (ROS) are light-dependent, the time- and concentration-specific induction
of oxidative stress was investigated in leaves of tomato plants kept under light
and dark conditions after treatments with 0.1mM and 1mM SA. The application of
exogenous SA induced early superoxide- and H2O2 production in the leaves, which
was different in the absence or presence of light and showed time- and
concentration-dependent changes. 1mM SA, which induced HR-like cell death
resulted in two peaks in the H2O2 production in the light but the first, priming
peak was not detected in the dark. Unlike 0.1mM SA, 1mM SA application induced
NADPH oxidase activity leading to increased superoxide production in the first
hours of SA treatments in the light. Moreover, SA treatments inhibited catalase
(CAT) activity and caused a transient decline in ascorbate peroxidase (APX), the
two main enzymes responsible for H2O2 degradation, which led to a fast H2O2 burst
in the light. Their activity as well as the expression of some isoenzymes of SOD
and APX increased only from the 12th h in the illuminated samples. The activity
of NADPH oxidase and expression SlRBOH1 gene encoding a NADPH oxidase subunit was
much lower in the dark. In spite of low CAT and APX activity after SA treatments
in the dark, the activation of guaiacol-dependent peroxidase (POD) could
partially substitute H2O2 scavenging activity of these enzymes in the dark, which
reduced the ROS burst and development of lesion formation in the leaves.
PMID- 28423348
TI - A neurorestorative approach to Parkinson's disease.
PMID- 28423349
TI - M channels and stress response.
PMID- 28423350
TI - ATXN2 a culprit with multiple facets.
PMID- 28423351
TI - Significance of inflammation-based indices in the prognosis of patients with non
metastatic colorectal cancer.
AB - Previous studies demonstrated that several inflammation-based hematological
indices are closely related to various malignancies, including colorectal cancer
(CRC). In this study, the prognostic value of inflammation-based markers,
including a combination index termed coNLR-PDW, comprising the preoperative
neutrophil-to-lymphocyte ratio (NLR) and the platelet distribution width (PDW),
was evaluated in 206 patients with non-metastatic CRC treated with surgery at a
single medical center. The association of patient demographics, blood chemistry,
and serum biochemical indices with recurrence-free survival (RFS) and overall
survival (OS) were examined through univariate and multivariate analysis.
Receiver operating characteristic curve analysis revealed the optimal cut-off
values of the NLR and lymphocyte-to-monocyte ratio (LMR) to be, respectively, 2.0
and 3.32 for both RFS and OS. For PDW, cut-off values of 17.25% and 17.35% were
defined for RFS and OS, respectively. On univariate analysis, lymph node
involvement, stage, presence of intravascular emboli (IVE), carbohydrate antigen
199 (CA199) >= 35 kU/L, NLR >= 2.0, LMR <= 3.32, elevated PDW, a high coNLR-PDW
score, high blood glucose, and high neutrophil and lymphocyte percentages
correlated with poorer RFS and OS (P < 0.05). On multivariate analysis, lymph
node involvement, IVE, CA199, PDW, and coNLR-PDW correlated with both RFS and OS
(P < 0.05), while NLR correlated only with OS (P = 0.001). These results
highlight the usefulness of the coNLR-PDW index as a prognostic marker of non
metastatic CRC outcome. In clinical practice, its assessment could contribute to
establishing more personalized regimes for patients undergoing tumor resection
surgery.
PMID- 28423352
TI - Prospective serum metabolomic profile of prostate cancer by size and extent of
primary tumor.
AB - Two recent investigations found serum lipid and energy metabolites related to
aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate
whether those metabolomic profiles represent etiologic or tumor biomarker
signals, we prospectively examined serum metabolites of prostate cancer cases by
size and extent of primary tumors in a nested case-control analysis in the ATBC
Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4
(n = 15) disease to controls (n = 200). Time from fasting serum collection to
diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known
compounds, and logistic regression estimated odds ratios (ORs) associated with
one-standard deviation differences in log-metabolites. N-acetyl-3
methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with
T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 <= p <= 0.01). By
contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl
linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and
inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 <= p <= 0.003). Secondary bile
acid lipids, sex steroids and caffeine-related xanthine metabolites were
elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with
T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit
qualitatively different metabolite profiles years in advance of diagnosis that
may represent etiologic factors, molecular patterns reflective of distinct
primary tumors, or a combination of both.
PMID- 28423353
TI - Silencing PRDM14 expression by an innovative RNAi therapy inhibits stemness,
tumorigenicity, and metastasis of breast cancer.
AB - PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem
cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers,
it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic
changes to cancer cells. Here, we examined the phenotypic characteristics and
epigenetic and gene expression profiles of cancer cells that differentially
express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy.
PRDM14 expression was markedly increased in many different cancer types and
correlated with poor survival of breast cancer patients. PRDM14 conferred stem
cell-like phenotypes to cancer cells and regulated the expression of genes
involved in cancer stemness, metastasis, and chemoresistance. PRDM14 also reduced
the methylation of proto-oncogene and stemness gene promoters and PRDM14-binding
regions were primarily occupied by histone H3 Lys-4 trimethylation (H3K4me3),
both of which are positively correlated with gene expression. Moreover, strong
PRDM14 binding sites coincided with promoters containing both H3K4me3 and
H3K27me3 histone marks. Using calcium phosphate hybrid micelles as an RNAi
delivery system, silencing of PRDM14 expression by chimera RNAi reduced tumor
size and metastasis in vivo without causing adverse effects. Conditional loss of
PRDM14 function also improved survival of MMTV-Wnt-1 transgenic mice, a
spontaneous model of murine breast cancer. Our findings suggest that PRDM14
inhibition may be an effective and novel therapy for cancer stem cells.
PMID- 28423354
TI - CD54+ rabbit adipose-derived stem cells overexpressing HIF-1alpha facilitate
vascularized fat flap regeneration.
AB - Fat flap transplantation is frequently performed in patients suffering from soft
tissue defects resulting from disease or trauma. This study explored the
feasibility of constructing vascularized fat flaps using rabbit adipose-derived
stem cells (rASCs) and collagen scaffolds in a rabbit model. We evaluated rASCs
proliferation, paracrine function, adipogenesis, vascularization, and CD54
expression, with or without HIF-1alpha transfection in vitro and in vivo. We
observed that adipogenic differentiation potential was greater in rASCs with high
CD54 expression (CD54+rASCs) than in those with low expression (CD54-rASCs), both
in vitro and in vivo. HIF-1alpha overexpression not only augmented this effect,
but also enhanced cell proliferation and paracrine function in vitro. We also
demonstrated that HIF-1alpha-transfected CD54+rASCs showed enhanced paracrine
function and adipogenic capacity, and that paracrine function increases
expression of angiogenesis-related markers. Thus, CD54+rASCs overexpressing HIF
1alpha enhanced large volume vascularized fat flap regeneration in rabbits,
suggesting CD54 may be an ideal candidate marker for ASCs adipogenic
differentiation.
PMID- 28423355
TI - Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells
and promote angiogenesis.
AB - Mesenchymal stem cells (MSCs) have been found to benefit patients with a variety
of ischemic diseases via promoting angiogenesis. It is also well established that
exosomes secreted from MSCs deliver bioactive molecules, including microRNAs
(miRs) to recipient cells. Therefore, we hypothesized that exosomes secreted from
MSCs deliver miRs into endothelial cells and mediate angiogenesis. The pro
angiogenic stimulatory capacity of exosomes was investigated using tube-like
structure formation and spheroid-based sprouting of human umbilical vein
endothelial cells (HUVECs), and in vivo Matrigel plug assay. The secretion of pro
angiogenic miRs (pro-angiomiRs) from MSCs into culture medium and transfer of the
miRs to HUVECs were confirmed using real-time quantitative PCR. Supplementation
of the exosome secretion blocker GW4869 (10 MUM) reduced the pro-angiomiRs in the
MSC-derived conditioned medium (CdMMSC). Addition of exosomes isolated from
CdMMSC could directly 1) promote HUVEC tube-like structure formation in vitro; 2)
mobilize endothelial cells into Matrigel plug subcutaneously transplanted into
mice; and 3) increase blood flow inside Matrigel plug. Fluorescence tracking
showed that the exosomes were internalized rapidly by HUVECs causing an
upregulated expression of pro-angiomiRs in HUVECs. Loss-and-gain function of the
pro-angiomiRs (e.g., miR-30b) in MSCs significantly altered the pro-angiogenic
properties of these MSC-derived exosomes, which could be associated with the
regulation of their targets in HUVECs. These results suggest that exosomal
transfer of pro-angiogenic miRs plays an important role in MSC mediated
angiogenesis and stem cell-to-endothelial cell communication.
PMID- 28423356
TI - Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by
promoting the formation of Apaf-1-caspase-9 complex.
AB - MicroRNAs have been proved to participate in multiple biological processes in
cancers. For developing resistance to cytotoxic drug, cancer cells, especially
the cancer stem cells, usually change their microRNA expression profile to
survive in hostile environments. In the present study, we found that expression
of microRNA-27a was increased in colorectal cancer stem cells. High level of
microRNA-27a was indicated to induce the resistance to TNF-related apoptosis
inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer
stem cells to TRAIL-induced cell death. Mechanically, the gene of Apaf-1, which
is associated with the mitochondrial apoptosis, was demonstrated to be the target
of microRNA-27a in colorectal cancer stem cells. Knockdown of microRNA-27a
increased the expression level of Apaf-1, thus enhancing the formation of Apaf-1
caspase-9 complex and subsequently promoting the TRAIL-induced apoptosis in
colorectal cancer stem cells. These findings suggested that knockdown of microRNA
27a in colorectal cancer stem cells by the specific antioligonucleotides was
potential to reverse the chemoresistance to TRAIL. It may represent a novel
therapeutic strategy for treating the colorectal cancer more effectively.
PMID- 28423357
TI - MiR-29b inhibits the growth of glioma via MYCN dependent way.
AB - MiR-29b is widely involved in diverse cancers. We plan to study its role in
glioma. The expression of miR-29b was detected by real-time polymerase chain
reaction (PCR) and we found the expression of miR-29b was decreased in glioma.
Cell proliferation was evaluated by cell counting kit (CCK8) and 5-Ethynyl-2'-
deoxyuridine (EdU) and cell apoptosis was assayed with flow cytometry assay
(FCA), which indicated miR-29b can inhibit the proliferation and promote the
apoptosis of glioma cells. The target of miR-29b was predicted using miRanda,
TargetScan and PicTar sofeware and we also found MYCN was a direct target of miR
29b in glioma cells and miR-29b inhibited the proliferation of glioma cells via
MYCN dependent way. Subcutaneous xenotransplantation model was designed to
investigate the affection of miR-29b on glioma growth. The effectiveness of miR
29b for glioma prediction was also performed and we determined miR-29b can stably
exist and may act as a biomarker for the diagnosis of glioma. As a conclusion,
miR-29b inhibits the growth of glioma via MYCN dependent way and can be a
biomarker for the diagnosis of glioma.
PMID- 28423358
TI - Characterization of fusion genes in common and rare epithelial ovarian cancer
histologic subtypes.
AB - Gene fusions play a critical role in some cancers and can serve as important
clinical targets. In epithelial ovarian cancer (EOC), the contribution of
fusions, especially by histological type, is unclear. We therefore screened for
recurrent fusions in a histologically diverse panel of 220 EOCs using RNA
sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to
identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA)
tumors. Associations between fusions and clinical prognosis were evaluated using
Cox proportional hazards regression models. Nine recurrent fusions, defined as
occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most
frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This
fusion was not associated with survival; other recurrent fusions were too rare to
warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique
to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some
evidence that CC tumors harbor more fusions on average than any other EOC
histological type, including high-grade serous (HGS) tumors. CC tumors harbored a
mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC
tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in
endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean =
0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10%
frequency in the CC EOC subtype, but find little evidence for common (> 5%
frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC
tumors.
PMID- 28423359
TI - Epithelial-mesenchymal transition induced by GRO-alpha-CXCR2 promotes bladder
cancer recurrence after intravesical chemotherapy.
AB - Non-muscle invasive bladder cancers (NMIBC) are typically treated by
transurethral resection with intravesical chemotherapy. However, the post
therapeutic incidence of tumor recurrence and progression to muscle invasive
disease is high, and the underlying mechanism(s) remains unknown. In this study,
we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype,
which is initiated by the autocrine GRO-alpha signaling. Mechanically, the
chemotherapeutic drug epidoxorubicin induces GRO-alpha expression in primary
bladder cancer cells at G1/S phase via p38-dependent activation of NF-kappaB. GRO
alpha phosphorylation of Snail on Ser246 supports Snail's accumulation in the
nucleus, and thereby promotes transcription repression activity of Snail from E
cadherin promoters. In accordance, disrupting the GRO-alpha-Snail axis in NMIBC
represents a promising alternative to prevent post-therapeutic tumor progression
and recurrence.
PMID- 28423360
TI - TIAM1 variants improve clinical outcome in neuroblastoma.
AB - Identification of tumor driver mutations is crucial for improving clinical
outcome using a personalized approach to the treatment of cancer. Neuroblastoma
is a tumor of the peripheral sympathetic nervous system for which only a few
driver alterations have been described including MYCN amplification and ALK
mutations. We assessed 106 primary neuroblastoma tumors by next generation
sequencing using a customized amplicon-based gene panel. Our results reveal that
genetic variants in TIAM1 gene associate with better clinical outcome, suggesting
a role for these TIAM1 variants in preventing progression of this disease. The
detected variants are located within the different domains of TIAM1 that signal
to the upstream regulator RAS and downstream effector molecules MYC and RAC,
which are all implicated in neuroblastoma etiology and progression. Clinical
outcome was improved in tumors where a TIAM1 variant was present concomitantly
with either ALK mutation or MYCN amplification. Given the function of these
signaling molecules in cell survival, proliferation, differentiation and neurite
outgrowth, our data suggest that the TIAM1-mediated network is essential to
neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for
improving therapy efficacy in neuroblastoma.
PMID- 28423361
TI - Next-generation sequencing reveals microRNA markers of adrenocortical tumors
malignancy.
AB - BACKGROUND: Adrenocortical carcinoma is a rare finding among common
adrenocortical tumors, but it is highly aggressive and requires early detection
and treatment. Still, the differential diagnosis between benign and malignant
lesions is difficult even for experienced pathologists and there is a significant
need for novel diagnostic methods. In this study we aimed to reveal a complete
set of microRNAs expressed in the adrenal gland and to identify easily
detectable, stable and objective biomarkers of adrenocortical malignancy.
METHODS: We employed next-generation sequencing to analyze microRNA profiles in a
unique set of 51 samples, assigned to either a learning dataset including 7
adrenocortical carcinomas (ACCs), 8 adrenocortical adenomas (AAs) and 8 control
samples (NAs), or a validation dataset including 8 ACCs, 10 AAs and 10 NAs. The
results were validated in real-time Q-PCR. RESULTS: We detected 411 miRNAs
expressed in 1763 length isoforms in the examined samples. Fifteen miRNAs
differentiate between malignant (ACC) and non-malignant (AA + NA) tissue in the
test set of independent samples. Expression levels of 6 microRNAs, miR-503-5p,
miR-483-3p, miR-450a-5p, miR-210, miR-483-5p, miR-421, predict sample status
(malignancy/non-malignancy) with at least 95% accuracy in both datasets. The best
single-gene malignancy marker, miR-483-3p, has been validated by real-time RT
PCR. CONCLUSIONS: As a result of the study we propose clinically valid and easily
detectable biomarkers of adrenocortical malignancy that may significantly
facilitate morphological examination. Since microRNAs can be detected in blood,
the study brings tools for development of non-invasive diagnostics of
adrenocortical carcinomas.
PMID- 28423362
TI - TROP2 promotes proliferation, migration and metastasis of gallbladder cancer
cells by regulating PI3K/AKT pathway and inducing EMT.
AB - The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many
cancers. However, its effect on proliferation, migration and metastasis of
gallbladder cancer remains unclear. In this study, we found that TROP2 was highly
expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor
prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited
the cell proliferation, clone formation, invasion and migration in vitro, while
TROP2 overexpression had opposite effects. In addition, knockdown of TROP2
increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via
PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E
cadherin expression during epithelial-mesenchymal transition (EMT). Moreover,
gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors
in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt
phosphorylation, increased PTEN expression and postponed EMT of gallbladder
cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the
proliferation, migration and metastasis of gallbladder cancer cells by regulating
PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic
biomarker and therapeutic target for the clinical management of gallbladder
cancer.
PMID- 28423363
TI - Multiple-gene panel analysis in a case series of 255 women with hereditary breast
and ovarian cancer.
AB - As new genes predisposing to breast (BC) and ovarian cancer (OC) are constantly
emerging, the use of panels of genes analyzed by Next-Generation Sequencing (NGS)
is increasing in clinical diagnostics. The identification of a large number of
new germline mutations allows for deeper knowledge of cancer predisposition,
although raising many questions about patient management.BC and OC patients
recruited by our counseling service between 2012-2015 were included in this
study. DNA was extracted from peripheral blood and a panel of 94 genes involved
in hereditary tumors was analyzed by NGS. Patient clinical features of BC and OC
and cancer family history were collected and compared to the patient genetic
profile.A total of 255 women were analyzed, 57 of whom had a pathogenic mutation
in BRCA1/2 genes, and 17 carried pathogenic mutations in other genes, such as
PALB2, ATM, BRIP1, RAD51D, MSH6, PPM1D, RECQL4, ERCC3, TSC2, SLX4 and other
Fanconi anemia genes.Patients with a pathogenic mutation in genes other than
BRCA1 and BRCA2 showed no significant difference from the BRCA1/2-mutated
carriers with respect to age at diagnosis and clinical features, suggesting that
mutations in other genes could pose a high risk of cancer development.These
patients had a much higher percentage of bilateral breast cancer (BBC) and a
lower rate of OC than BRCA-mutated patients and patients with no pathogenic
mutations: as a consequence, the surveillance protocol should be customized to
the patient genetic characteristics.
PMID- 28423364
TI - Increased expression of deleted in malignant brain tumors (DMBT1) gene in
precancerous gastric lesions: Findings from human and animal studies.
AB - Helicobacter pylori infection triggers a cascade of inflammatory stages that may
lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal
metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1)
belongs to the group of secreted scavenger receptor cysteine-rich proteins and is
considered to be involved in host defense by binding to pathogens. Initial
studies showed its deletion and loss of expression in a variety of tumors but the
role of this gene in tumor development is not completely understood. Here, we
examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African
American and Hispanic individuals as well as in the development of gastric
pathology in a mouse model of H. pylori infection. We found that in 3 different
populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in
individuals with dysplasia compared to multifocal atrophic gastritis without
intestinal metaplasia; the increase was also observed in individuals with
advanced gastritis and positive H. pylori infection. In our animal model, H.
pylori infection of Dmbt1-/- mice resulted in significantly higher levels of
gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in
the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the
animal model suggest that in response to H. pylori infection DMBT1 may mediate
mucosal protection reducing the risk of developing gastric precancerous lesions.
However, the increased expression in human gastric precancerous lesions points to
a more complex role of DMBT1 in gastric carcinogenesis.
PMID- 28423365
TI - Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival of
epithelial ovarian cancer: a systematic review and meta-analysis of observational
studies.
AB - Inflammation plays an important role in the development and progression of
epithelial ovarian cancer (EOC). However, no meta-analysis has comprehensively
and quantitatively investigated the prognostic value of the neutrophil-to
lymphocyte ratio (NLR) in EOC patients. Therefore, we performed a meta-analysis
to quantify the prognostic impact of this biomarker. We searched the PubMed and
Web of Science databases from their inception through December 31, 2016, and
examined observational studies evaluating the association of preoperative NLR
with progression-free survival (PFS) and overall survival (OS) of EOC patients. A
random-effects model was used to summarize hazard ratios (HRs) with 95%
confidence intervals (CIs). Twelve retrospective cohort studies including 3,154
EOC patients were identified. Elevated NLR in EOC patients was associated with
worse PFS (summarized HR=1.80; 95% CI = 1.22-2.65; I2 = 79.1%) and OS (summarized
HR = 1.72; 95% CI = 1.18-2.51; I2 = 73.5%) compared with low NLR. No evidence of
publication bias was detected by funnel plot analysis and formal statistical
tests. Although the results were robust in all subgroup analyses, not all results
were statistically significant. We determined that adjustments for CA-125 level
and performance status might be sources of heterogeneity. These combined results
indicate that preoperative NLR is an important predictor of prognosis in EOC
patients. Since the high heterogeneity and retrospective study design of included
studies, these results require further validation with prospective cohort and
trials enrolling larger patient populations and conducting longer follow-up
examinations.
PMID- 28423366
TI - Legume intake and risk of prostate cancer: a meta-analysis of prospective cohort
studies.
AB - Previous studies regarding the relationship between legume intake and risk of
prostate cancer have reported inconsistent results. We conducted a meta-analysis
of prospective cohort studies to summarize evidence on this association. A
systematic literature search of articles published through June 2016 was
performed using PubMed and Web of Science databases. The combined relative risk
(RR) with its 95% confidence interval (CI) for the highest versus the lowest
intake of legumes was calculated with a random-effects model. Dose-response meta
analysis was also performed for the studies that provided at least three levels
of legume consumption. Ten articles (eight cohorts) reporting 281,034 individuals
and 10,234 incident cases were identified. The individuals with high consumption
of legumes compared with the reference group experienced a significantly reduced
risk for developing prostate cancer (RR: 0.85 [95% CI 0.75-0.96], P = 0.010).
Moderate heterogeneity of RRs was observed across these studies (P = 0.064 for
heterogeneity, I2 = 45.8 %). Dose-response meta-analysis indicated that the risk
of prostate cancer reduced by 3.7% (95% CI 1.5%-5.8%) for each 20 grams per day
increment of legume intake. In conclusion, the results from this meta-analysis
suggest that a high intake of legumes is associated with a low incidence of
prostate cancer.
PMID- 28423368
TI - The effects of herbal medicine on epilepsy.
AB - Traditional herbal medicine plays a significant role in the treatment of
epilepsy. Though herbal medicine is widely used in antiepileptic treatment, there
is a lack of robust evidence for efficacy and toxicity of most herbs. Besides,
the herbal medicine should be subject to evidence-based scrutiny. In this
context, we present a review to introduce the effects of herbal medicine on
epilepsy. However, hundreds of herbal medicines have been investigated in the
available studies. Some commonly used herbal medicines for epilepsy have been
listed in our study. The overwhelming majority of these data are based on animal
experiments. The lack of clinical data places constraints on the clinical
recommendation of herbal medicine. Our study may conduct further studies and
provide some insight on the development of anti-epileptic drugs.
PMID- 28423369
TI - MDI 301, a synthetic retinoid, depressed levels of matrix metalloproteinases and
oxidative stress in diabetic dermal fibroblasts.
AB - Diabetic foot ulcerations could result in serious consequences such as
amputations. The up-regulation of matrix metalloproteinases and down-regulation
of TIMP1 were remarked as distinctive biological characteristics in the diabetic
dermal fibroblast. The current study was performed in order to clarify the effect
of high glucose on formation of diabetic dermal fibroblast cell. In addition, the
effect of MDI 301 on ameliorating diabetic fibroblasts was investigated in this
study. The mRNA and protein expression levels of MMPs, TIMP1 and catalase were
evaluated against fibroblasts treated with high glucose (30 mM) using qRT-PCR,
western blotting and zymography assays. Methods were also employed for
investigating the biological effects of MDI 301 on high glucose-induced diabetic
fibroblasts. In this study, we found that the unbalance of oxidative stress
induced by high glucose concentration play an important role in the formation of
diabetic dermal fibroblast from normal cells. In addition, MDI 301, a picolinic
acid-substituted ester of 9-cis retinoic acid was employed in this study in order
to ameliorate symptoms on diabetic dermal fibroblast induced by high glucose
concentration. We found MDI 301 alleviate the effects of high glucose-induced
skin damage by balancing the oxidative stress and regulating the MMPs and TIMP1
levels. Our finding indicated that MDI 301 offers the potential for repairing the
faulty skin function arising from diabetes.
PMID- 28423370
TI - Transarterial chemoembolization combined with Jie-du granule preparation improves
the survival outcomes of patients with unresectable hepatocellular carcinoma.
AB - The aim of the present study was to compare the effectiveness of transarterial
chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE
combined with sorafenib (SOR) for treating patients with unresectable
hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective
analysis of data from 266 consecutive patients with unresectable HCC who
underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery
Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient
survival and progression times as well as independent predictors, within a follow
up period of 86 months. Patients were divided into TACE-JD (n = 75), TACE-SOR (n
= 124) and TACE (n = 67) groups. Median overall survival (OS) times being: TACE
JD, 21.43 months; TACE-SOR, 23.23 months; TACE, 13.97 months (TACE-SOR vs TACE, P
< 0.001; TACE-SOR vs TACE-JD, P = 0.852; TACE-JD vs TACE, P < 0.001). The median
times to progression (TTP) were as follows: TACE-JD, 8.67 months; TACE-SOR, 5.37
months; TACE, 4.57 months (TACE-SOR vs TACE, P = 0.479; TACE-SOR vs TACE-JD, P <
0.001; TACE-JD vs TACE, P < 0.001). Independent predictors of OS were treatment
allocation, Child-Pugh class large tumor, albumin and extrahepatic metastasis.
These findings show that patients with unresectable HCC who were administered
TACE-JD survived significantly longer compared with those administered TACE or
TACE-SOR.
PMID- 28423371
TI - Subjective Technology Adaptivity Predicts Technology Use in Old Age.
AB - BACKGROUND: To date, not much is known about the psychological and motivational
factors underlying technology use in late life. What are the interindividual
determinants that lead older adults to invest in using technological innovations
despite the age-related physiological changes that impose challenges on
behavioral plasticity in everyday life? OBJECTIVE: This research explores
interindividual differences in subjective technology adaptivity - a general
technology-related motivational resource that accounts for technology use in late
life. More specifically, we investigate the influence of this factor relative to
demographic characteristics, personality traits, and functional limitations in a
longitudinal sample of community-dwelling older adults. METHODS: We report
results from a paper-and-pencil survey with 136 older adults between 59 and 92
years of age (mean = 71.4, SD = 7.4). Of those participants, 77 participated in a
2-year follow-up. We assessed self-reports of technology use, subjective
technology adaptivity, functional limitations, and the personality traits
openness to new experiences and neuroticism. RESULTS: Higher levels of subjective
technology adaptivity were associated with technology use at the first
measurement as well as increased use over the course of 2 years. CONCLUSIONS:
Subjective technology adaptivity is a significant predictor of technology use in
old age. Our findings contribute to improving the understanding of
interindividual differences when using technological innovation in late life.
Moreover, our findings have implications in the context of user involvement and
may contribute to the successful development of innovative technology for older
adults.
PMID- 28423372
TI - Patterns of Disease in Patients with Middle-Lobe Predominant Bronchiectasis.
AB - BACKGROUND: Middle-lobe predominant bronchiectasis affecting the right middle
lobe and/or lingula (RMLP) is classically described in asthenic, elderly females
with skeletal abnormalities or associated nontuberculous mycobacterial (NTM)
infection. OBJECTIVES: We aimed to evaluate the frequency and clinical
characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed
bronchiectasis patients and determine associations with disease severity.
METHODS: A retrospective observational cross-sectional cohort study of
consecutive bronchiectasis patients in our institution was performed. Data were
collected on baseline variables, microbiology status, lung function, and
radiology according to the modified Bhalla score. Disease severity was assessed
using bronchiectasis severity index (BSI) and FACED severity scores. RESULTS: Of
81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20
(24.7%) had RMLP disease. These patients were significantly younger, female, and
with lower BMIs than patients with the classical bronchiectasis phenotype (p =
0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum
(p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher
baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of
NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in
RMLP patients were significantly lower than their counterparts (both p < 0.001).
CONCLUSIONS: The RMLP phenotype is associated with younger patients than
classically described in the literature. An increased rate of NTM infection in
this phenotype was noted, particularly in females, but much lower than previously
described. Lung function and disease severity scores in this patient group are
relatively normal, suggesting a milder phenotype in patients with this form of
the disease.
PMID- 28423373
TI - Distribution of Interstitial Telomeric Sequences in Primates and the Pygmy Tree
Shrew (Scandentia).
AB - It has been hypothesized that interstitial telomeric sequences (ITSs), i.e.,
repeated telomeric DNA sequences found at intrachromosomal sites in many
vertebrates, could be correlated to chromosomal rearrangements and plasticity. To
test this hypothesis, we hybridized a telomeric PNA probe through FISH on
representative species of 2 primate infraorders, Strepsirrhini (Lemur catta,
Otolemur garnettii, Nycticebus coucang) and Catarrhini (Erythrocebus patas,
Cercopithecus petaurista, Chlorocebus aethiops, Colobus guereza), as well as on 1
species of the order Scandentia, Tupaia minor, used as an outgroup for primates
in phylogenetic reconstructions. In almost all primate species analyzed, we found
a telomeric pattern only. In Tupaia, the hybridization revealed many bright ITSs
on at least 11 chromosome pairs, both biarmed and acrocentric. These ITS signals
in Tupaia correspond to fusion points of ancestral human syntenic associations,
but are also present in other chromosomes showing synteny to only a single human
chromosome. This distribution pattern was compared to that of the heterochromatin
regions detected through sequential C-banding performed after FISH. Our results
in the analyzed species, compared with literature data on ITSs in primates,
allowed us to discuss different mechanisms responsible for the origin and
distribution of ITSs, supporting the correlation between rearrangements and ITSs.
PMID- 28423374
TI - Hyperbaric Oxygen Therapy as Adjuvant Treatment for Idiopathic Sudden
Sensorineural Hearing Loss after Failure of Systemic Steroids.
AB - We evaluated the outcomes of and prognostic factors for idiopathic sudden
sensorineural hearing loss (ISSNHL) treated with adjuvant hyperbaric oxygen
therapy (HBOT). A retrospective review of clinical data was performed for 167
patients with ISSNHL who failed to respond to systemic steroids and were treated
by adjuvant HBOT at Shizuoka Saiseikai General Hospital. We analysed the clinical
outcomes, the averaged 5-frequency hearing level after systemic steroids, patient
age, the interval between post-steroids and pre-HBOT, vertigo as a complication,
the presence of diabetes mellitus, smoking history, and hypertension. Overall,
after HBOT, complete recovery occurred in 16 (9.6%) of the patients, with
definite improvement in 16 (9.6%) and slight improvement in 45 (26.9%). The
overall rate of hearing improvement was higher in the study group (77/167 cases,
46.1%) than in the control group (52/160 cases, 32.5%; p = 0.021). If performed
appropriately, HBOT should be able to improve hearing in many cases unresponsive
to initial therapy.
PMID- 28423375
TI - Evaluation of Short-Term Efficacy of Concurrent Chemoradiotherapy in Primary
Fallopian Tube Carcinoma by Diffusion-Weighted Imaging: A Retrospective Study.
AB - BACKGROUND: This study aims to evaluate the short-term efficacy of concurrent
chemoradiotherapy (CCRT) in primary fallopian tube carcinoma (PFTC) using
magnetic resonance diffusion-weighted imaging (MR-DWI). PATIENTS AND METHODS:
Total abdominal irradiation was performed for 61 PFTC patients after surgery, and
paclitaxel and carboplatin were used for CCRT. According to the response
evaluation criteria in solid tumors (RECIST1.1), patients were divided into a
sensitive (n = 36) and a resistant group (n = 25). Pearson correlation analysis
was conducted to assess the correlations of tumor regression rate with apparent
diffusion coefficient (ADC)pre, ADCpost, and ?ADCpost. The efficacy of CCRT in
PFTC using MR-DWI was evaluated by ROC curve, logistic regression analysis,
Kaplan-Meier survival curve, and Cox regression model. RESULTS: The ADCpre in
both the sensitive and the resistant group was negatively associated with the
tumor regression rate (r = -0.508), while the ADCpost (r = 0.454) and ?ADCpost (r
= 0.769) were positively associated with the tumor regression rate (all p <
0.05). Histopathological type, FIGO stage, lymphatic metastasis, tumor regression
rate, ADCpre, ADCpost, and ?ADCpost were confirmed as key factors for CCRT in
PFTC (all p < 0.05). CONCLUSION: Our retrospective study demonstrates the
predictive value of MR-DWI in CCRT for PFTC patients.
PMID- 28423376
TI - Controlled Pressure: The Solution for a High-Pressure Situation - Aetiology and
Techniques for Control of Airway Haemorrhage.
PMID- 28423377
TI - Risk and Survival of Patients with Head and Neck Cutaneous Melanoma: National
Perspective.
AB - OBJECTIVE: Head and neck cutaneous melanoma represents a distinct entity of skin
cancer. We aim to examine management and survival of patients with head and neck
cutaneous melanoma. METHODS: A retrospective cohort study utilizing the National
Cancer Database, 2004-2012. RESULTS: A total of 20,322 (21.2%) head and neck
melanomas and 75,547 (78.8%) melanomas of other sites were included. The median
follow-up time of head and neck melanoma was 41.6 months (interquartile range:
22.9-68.2 months). Patients with melanoma of the head and neck were more likely
to be >=65 years old, male, and/or white (p < 0.001 each). Positive surgical
margin was more prevalent in head and neck melanoma [OR: 2.19, 95% CI: (2.03,
2.37)], and was associated with a lower survival [HR: 1.41, 95% CI: (1.28,
1.57)]. High positive lymph node ratio was associated with a lower survival [HR:
2.00, 95% CI: (1.13, 3.57)]. Adjuvant immunotherapy was associated with an
improved survival [HR: 0.67, 95% CI: (0.57, 0.80)]. CONCLUSION: Head and neck
cutaneous melanoma is associated with certain demographics. Surgical margin
status, lymph node ratio, and immunotherapy are independently associated with
overall survival.
PMID- 28423378
TI - Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on
Microenvironment Modulation.
AB - Cutaneous T-cell lymphomas (CTCL) are a rare and biologically heterogeneous
malignant entity comprising mycosis fungoides and Sezary syndrome as the most
common subtypes. The current treatment outcome is characterized by high rates of
relapse, but survival is usually not significantly shortened in low-stage
disease. This is different in tumor-stage disease or aggressive CTCL subtypes
where survival is significantly reduced. Recent advances have been made on
several levels of tumor biology: Whole genome sequencing has resulted in novel
strategies of NF-kappaB or JAK inhibition, ongoing translational research has
revealed new targets like CD30 or CCR4, and, finally, research focusing on
impaired immunosurveillance has gained more importance. Based on the growing
knowledge about the functional roles of the tumor microenvironment and non
malignant infiltrating cells, current research aims to develop novel CTCL
treatment strategies. This review focuses on the mounting evidence for
efficiently targeting tumor-infiltrating immune cells and thereby modulating the
tumor microenvironment and restoring immunosurveillance.
PMID- 28423379
TI - Excessive Weight Favours Skin Physiology - Up to a Point: Another Expression of
the Obesity Paradox.
AB - BACKGROUND/AIMS: Recently classified as an epidemic by the WHO, obesity (as well
as the state of being overweight) clearly affects significant populations across
all ages. The relationship between obesity and some diseases (e.g. cardiovascular
ones) is known, although many paradoxes remain to be explained. Very little
information is available, however, regarding its impact on skin physiology and
skin disease. This study aims to examine the influence of excessive weight on
epidermal hydration and transepidermal water loss, key variables of skin water
balance and skin biomechanics. METHODS: A convenience sample of 89 healthy female
volunteers was selected and divided into 4 groups, according to their BMI (body
mass index), as normal (control), overweight, obese (I and II), and morbid. Skin
physiology was quantitatively assessed in all individuals in 4 anatomical areas
using non-invasive biometrical analysis by reference instrumentation. Descriptive
and comparative statistics were applied, adopting a confidence level of 95%.
RESULTS: A non-linear alteration for all variables was detected as a function of
BMI. CONCLUSION: Results suggest that excessive weight might favour skin
performance within certain limits, reflecting a particular adaptation of the skin
to the weight gain and body contour.
PMID- 28423380
TI - A Systematic Review of Symptoms and Quality of Life Issues in Pancreatic
Neuroendocrine Tumours.
PMID- 28423381
TI - Self-Administered Tinnitus Pitch Matching versus a Conventional Audiometric
Procedure.
AB - OBJECTIVE: Obtaining an accurate tinnitus pitch match is an initial and critical
requirement for tinnitus evaluation and treatment, particularly for applying
tailor-made notched music training. We investigated whether computer-based self
administered tinnitus pitch matching (CSTPM) is comparable with a conventional
audiometric procedure (CAP). METHODS: In total, 82 patients (mean age 45.52
years; 42 females) with tonal tinnitus participated. The CAP was performed by the
same audiologist using a 2-alternative forced choice method with a frequency
range of 0.25-16 kHz. In the CSTPM, the subjects used personal computer software
with a scrolling slider to select the sound closest to their tinnitus pitch.
After each matching procedure, an octave challenge test was applied. A
multivariate logistic regression was performed to determine factors associated
with the difference between the CSTPM and CAP. RESULTS: The subjects' mean
hearing threshold was 21.25 +/- 17.61 dB HL; the mean tinnitus handicap inventory
score was 35.56 +/- 24.09. The mean pitches measured with the CSTPM and CAP were
6.29 +/- 4.30 and 6.98 +/- 5.33 kHz, respectively. In total, 57 (69.5%) subjects
matched their tinnitus with less than half an octave difference between the
procedures. The results of the 2 methods correlated significantly with each other
(Pearson r = 0.793, p < 0.001). Octave confusion was a significant factor
affecting the difference between the procedures (odds ratio 8.92, p < 0.05).
CONCLUSIONS: The CSTPM appears to be as accurate as the standard audiological
procedure, and may be used instead of the CAP when octave confusion is minimized.
PMID- 28423382
TI - Late Recurrence of Early Stage Cervical Cancer more than 3 Years after Radical
Hysterectomy with Pelvic Node Dissection.
AB - BACKGROUND: The aim of this study was to compare the clinicopathological
characteristics and outcomes of patients who developed late recurrence (> 3
years) of early stage cervical cancer after radical surgery with those of
patients who developed early recurrence (<= 3 years). We also investigated the
risk factors of late recurrence. METHODS: The records of 515 patients with early
stage cervical cancer diagnosed between 1999 and 2015 were reviewed. 53 patients
developed recurrence, 35 early and 18 late, and their clinicopathological
characteristics and outcomes were compared. Of the 515 patients, the records for
307 patients who remained tumor free for at least 3 years after radical surgery
were further examined. RESULTS: No significant differences were found in
clinicopathological characteristics and clinical outcomes between the early and
late recurrence groups with regard to age, stage, histology, tumor size,
lymphovascular space invasion, stromal invasion, parametrial involvement, node
status, vaginal margin, preoperative blood testing, adjuvant therapy, symptom
status at recurrence, site of recurrence and survival after recurrence. Late
recurrence was detected in 18 of the 307 patients (5.9%). Only node status and
deep stromal invasion (DSI) were independently associated with late recurrence.
CONCLUSION: Lymph node metastasis and DSI are risk factors for late recurrence.
Careful long-term follow-up is needed, particularly in cases with lymph node
metastasis and/or DSI.
PMID- 28423383
TI - Remarkable Advances in the Management of Mycosis Fungoides and the Sezary
Syndrome.
PMID- 28423384
TI - Cetuximab-Carboplatin-5-Fluorouracil Regimen in Elderly Patients with Recurrent
or Metastatic Head and Neck Squamous-Cell Carcinoma: A French Retrospective
Survey.
AB - BACKGROUND: The cetuximab plus platinum-based chemotherapy regimen is a standard
of care in the treatment of recurrent or metastatic head and neck squamous-cell
carcinoma (HNSCC). The feasibility in the elderly population is currently
unknown. METHODS: We performed a retrospective study in order to assess the
efficacy and safety of the cetuximab plus platinum-based chemotherapy regimen in
patients >65 years with recurrent or metastatic HNSCC. We performed a
retrospective review of all medical records from recurrent or metastatic HNSCC
patients >65 years treated with the cetuximab plus platinum-based chemotherapy
regimen between September 2008 and December 2013 in our institution (Centre Paul
Strauss, Strasbourg, France). RESULTS: A total of 59 patients were identified.
Carboplatin in combination with 5-fluorouracil (FU) was the only cetuximab
associated chemotherapy regimen used for treating elderly patients. The median
progression-free survival was 4 months (95% confidence interval [CI]: 2.9-4.7),
and the median overall survival was 9.1 months (95% CI: 6.5-13.1). Grade 3 or 4
toxicity adverse events occurred in 52% (n = 31) of the patients (mostly
hematologic toxicities and infections). CONCLUSIONS: This retrospective study
suggests that the cetuximab plus carboplatin-5FU chemotherapy is an effective
treatment option for elderly patients with recurrent or metastatic HNSCC.
PMID- 28423385
TI - Guidelines for the Management of Diabetic Macular Edema by the European Society
of Retina Specialists (EURETINA).
AB - Diabetic retinal disease is envisioned to become the plague of the coming decades
with a steep increase of worldwide diabetes incidence followed by a substantial
rise in retinal disease. Improvements in diagnostic and therapeutic care have to
cope with this dilemma in a clinically and socioeconomically efficient manner.
Laser treatment has found a less destructive competitor in pharmacological
treatments. As a consequence of recent rigorous clinical trials, laser
photocoagulation is no longer recommended for the treatment of diabetic macular
edema (DME), and anti-vascular endothelial growth factor therapy has emerged as
first-line therapy. Steroids have maintained a role in the management of
chronically persistent DME. The paradigm shifts in therapy are accompanied by a
substantial break-through in diagnostics. The following guidance for the
management of DME has been composed from the best updated knowledge of leading
experts in Europe and represents another volume in the series of EURETINA
recommendations for the management of retinal disease.
PMID- 28423386
TI - Early Longitudinal Spectral Domain Optical Coherence Tomography Findings in
Subacute Sclerosing Panencephalitis.
PMID- 28423387
TI - Optical Coherence Tomography Angiography of Retinal Cavernous Hemangioma.
PMID- 28423388
TI - A National Study of the Effect of Race, Socioeconomic Status, and Gender on Burn
Outcomes.
AB - Age, burn size, and inhalation injury are the major contributing variables
related to burn mortality. While the female gender has been linked to higher
mortality, the impact of socioeconomic status has not been well studied. The
interplay between these three factors is also unknown. This study sought to
clarify the effects of these variables on outcomes in a national sample of
patients with burns. A retrospective review of 172,640 patient records of the
National Burn Repository (version 8, 2002-2011) data was conducted. Of those
records, 36,960 (21.4%) patient entries were excluded for duplicate entries,
follow-up visits, readmissions, nonburn injuries, skin diseases, and
incompleteness (missing date of admission, date of discharge, race, or TBSA of
burn or TBSA). Univariate and multivariate analyses were performed to compare
outcomes by race (Caucasian, African-American, and other minority groups). P <
.05 was considered significant. The study group included 135,680 patients and was
predominately Caucasian (59.0% Caucasian, 19.0% African-American, and 22.0% other
minority groups). The African-American race had more females, operations, longer
length of stay, ventilator days, septicemia (all P < .001), and urinary tract
infections (UTIs, P < .01). Caucasians had the largest burns (9.27 +/- 13.22, P
<.001) and were more likely to be older, to be intubated, and to have longer
intensive care unit stays and higher mortality (all P < .001). Other non-African
American minorities (other minority group) had the second largest burn sizes,
most uninsured members, and lowest mortality (P < .001). On multivariate
analysis, mortality was related to African-American race, female gender, TBSA,
full-thickness burn injury, inhalation injury, uninsured status, and burn
mechanism. African-Americans were 50% more likely to have complications (P <
.001), 30% more likely to have UTIs (P = .002), and 41% more likely to get
septicemia (P < .001). Other racial minority groups had more acute respiratory
distress syndrome, pneumonias, septicemia, UTIs, length of stay, and hospital
charges when compared with Caucasian patients. Socioeconomic status was related
to mortality but inconsistently related to other outcomes. Race appears to play a
significant role in burn injury outcomes. Minority groups, especially African
Americans, have a higher risk of morbidity and mortality compared with Caucasian
patients with burns. Socioeconomic status and gender also play a significant role
in burn outcomes. Future studies should focus on delineating the reasons for this
disparity.
PMID- 28423397
TI - Trends in Use of the US Medicare Annual Wellness Visit, 2011-2014.
PMID- 28423398
TI - Treatment Restarting After Discontinuation of Adjuvant Hormone Therapy in Breast
Cancer Patients.
AB - Background: Over half of breast cancer patients discontinue their adjuvant
hormone therapy, permanently or temporarily. We aimed to identify predictors of
treatment restarting after discontinuation of adjuvant hormone therapy and to
test the hypothesis that treatment restarting is associated with better breast
cancer outcomes. Methods: We conducted a population-based cohort study by linking
data from the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed
Drug Register, and a self-reported questionnaire. We followed women diagnosed
with breast cancer (Stockholm, Sweden, 2005-2008) from their first prescription
of tamoxifen or aromatase inhibitors through January 31, 2015, and categorized
them as continuers (n = 1 607), restarters (n = 953), and nonrestarters (n = 511)
of adjuvant hormone therapy. All statistical tests were two-sided. Results:
Factors that decrease the likelihood of treatment restarting included younger age
(<50 years), higher Charlson Comorbidity Score (>=2), smaller tumor size (<20
mm), human epidermal growth factor receptor 2 negative, lymph node negative,
family history of breast cancer negative, using hormone therapy, using symptom
relieving drugs, and switching therapy between tamoxifen and aromatase
inhibitors. Restarting adjuvant hormone therapy was statistically significantly
associated with prolonged disease-free survival, with an adjusted hazard ratio of
0.61 (95% confidence interval = 0.43 to 0.87, P = .006) for restarters vs
nonrestarters. Conclusions: Our study provides-for the first time to our
knowledge-evidence that restarting adjuvant hormone therapy is associated with
better breast cancer outcomes. Clinicians now have further evidence to encourage
patients to restart their treatment after discontinuation of adjuvant hormone
therapy.
PMID- 28423399
TI - Restarting Adjuvant Hormone Therapy Improves Breast Cancer Outcomes.
PMID- 28423400
TI - RE: Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma:
Survival Analyses of 6908 Cases From the National Cancer Data Base.
PMID- 28423401
TI - Response.
PMID- 28423403
TI - RE: The Association of Dyslipidemia With Chronic Lymphocytic Leukemia: A
Population-Based Study.
PMID- 28423404
TI - Response.
PMID- 28423402
TI - Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer.
AB - Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene
highly mutated in colorectal cancers (CRC). Mutation and inactivation of this
gene is a key and early event almost uniquely observed in colorectal
tumorigenesis. Alterations in the APC gene generate truncated gene products,
leading to activation of the Wnt signaling pathway and deregulation of multiple
other cellular processes. It has been a mystery why most patients with CRC retain
a truncated APC protein, but accumulating evidence suggest that these C
terminally truncated APC proteins may have gain of function properties beyond the
well-established loss of tumor suppressive function. Here, we will review the
evidence for both the loss of function and the gain of function of APC
truncations and how together they contribute to CRC initiation and progression.
PMID- 28423406
TI - The Rise of Radiomics and Implications for Oncologic Management.
AB - Clinical medicine, particularly oncology, is progressing toward personalized
care. Whereas the terms genomics, proteomics, transcriptomics, and metabolomics
have dominated personalized medicine for the past couple decades, the concept of
radiomics was first described in 2012. This nascent concept has major
implications for personalized cancer care and involves extracting hundreds of
standardized and quantifiable imaging characteristics from diagnostic computed
tomography/magnetic resonance imaging images. The central hypothesis of radiomics
is that these libraries of quantitative individual voxel-based variables are more
sensitively associated with various clinical endpoints compared with the more
qualitative radiologic, histopathologic, and clinical data more commonly utilized
today. Because radiomics offers immense potential but has not reached a
mainstream oncologic audience, the authors discuss herein the role of radiomics
in cancer care in the future.
PMID- 28423408
TI - The Patient Knows Best: Incorporating Patient-Reported Outcomes Into Routine
Clinical Care.
PMID- 28423407
TI - Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in
Lung Cancer Patients.
AB - Background: The use of web-based monitoring for lung cancer patients is growing
in interest because of promising recent results suggesting improvement in cancer
and resource utilization outcomes. It remains an open question whether the
overall survival (OS) in these patients could be improved by using a web-mediated
follow-up rather than classical scheduled follow-up and imaging. Methods:
Advanced-stage lung cancer patients without evidence of disease progression after
or during initial treatment were randomly assigned in a multicenter phase III
trial to compare a web-mediated follow-up algorithm (experimental arm), based on
weekly self-scored patient symptoms, with routine follow-up with CT scans
scheduled every three to six months according to the disease stage (control arm).
In the experimental arm, an alert email was automatically sent to the oncologist
when self-scored symptoms matched predefined criteria. The primary outcome was
OS. Results: From June 2014 to January 2016, 133 patients were enrolled and 121
were retained in the intent-to-treat analysis; 12 deemed ineligible after random
assignment were not subsequently followed. Most of the patients (95.1%) had stage
III or IV disease. The median follow-up was nine months. The median OS was 19.0
months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental
and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided P = .001)
(hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided P = .002). The performance
status at first detected relapse was 0 to 1 for 75.9% of the patients in the
experimental arm and for 32.5% of those in the control arm (two-sided P < .001).
Optimal treatment was initiated in 72.4% of the patients in the experimental arm
and in 32.5% of those in the control arm (two-sided P < .001). Conclusions: A web
mediated follow-up algorithm based on self-reported symptoms improved OS due to
early relapse detection and better performance status at relapse.
PMID- 28423409
TI - Different Breast Cancer Treatment Options Vary Widely in their Cost
Effectiveness.
PMID- 28423410
TI - Analysis of dislocation configurations in a [0 0 1] fcc single crystal by
electron channeling contrast imaging in the SEM.
AB - We have investigated the dislocation configurations in a [0 0 1] single crystal
of a face-centered alloy (316L stainless steel) by the electron channeling
contrast imaging (ECCI) technique in the scanning electron microscope under
controlled diffraction conditions. Specific dislocations such as piled-up
dislocations and Lomer-Cottrell dislocations were characterized by the analysis
of dislocation contrast and dislocation line trace analysis. The ECCI technique
also allows the sound estimation of the local resolved stress acting on gliding
dislocations by the analysis of the radius of curvature following a transmission
electron microscopy-based geometrical approach.
PMID- 28423411
TI - A convenient technique for live-cell observation on the surface of
polytetrafluoroethylene with a phase-contrast microscope.
AB - Phase-contrast microscopy is a convenient technique for live-cell observation on
the surface of materials with high optical transmittance. Here, we demonstrate a
novel technique to observe living cells on the surface of materials with low
optical transmittance, such as polytetrafluoroethylene (PTFE), which are widely
used in biomaterials for blood-contacting devices. The surface of a cover glass
was coated with a thin PTFE layer with sufficient transmittance, thereby enabling
the observation of living cells on the PTFE surface with a phase-contrast
microscope.
PMID- 28423412
TI - Brief presentation enhances various simultaneous contrast effects.
AB - Kaneko and Murakami (2012) demonstrated that simultaneous contrast for brightness
and color (chromatic saturation) were enhanced by flashing the stimulus very
briefly (10 ms). Here we examined whether this effect of duration generalized to
other visual features. Tilt illusion and simultaneous hue contrast were both
shown to be much stronger with a stimulus duration of 10 ms compared with 500 ms.
The similar temporal dynamics for simultaneous contrast across visual features
suggest common underlying principles.
PMID- 28423413
TI - Human perception of subresolution fineness of dense textures based on image
intensity statistics.
AB - We are surrounded by many textures with fine dense structures, such as human hair
and fabrics, whose individual elements are often finer than the spatial
resolution limit of the visual system or that of a digitized image. Here we show
that human observers have an ability to visually estimate subresolution fineness
of those textures. We carried out a psychophysical experiment to show that
observers could correctly discriminate differences in the fineness of hair-like
dense line textures even when the thinnest line element was much finer than the
resolution limit of the eye or that of the display. The physical image analysis
of the textures, along with a theoretical analysis based on the central limit
theorem, indicates that as the fineness of texture increases and the number of
texture elements per resolvable unit increases, the intensity contrast of the
texture decreases and the intensity histogram approaches a Gaussian shape.
Subsequent psychophysical experiments showed that these image features indeed
play critical roles in fineness perception; i.e., lowering the contrast made
artificial and natural textures look finer, and this effect was most evident for
textures with unimodal Gaussian-like intensity distributions. These findings
indicate that the human visual system is able to estimate subresolution texture
fineness on the basis of diagnostic image features correlated with subresolution
fineness, such as the intensity contrast and the shape of the intensity
histogram.
PMID- 28423414
TI - Discovery, Development, and Evaluation of a Horn Fly-Isolated (Diptera: Muscidae)
Beauveria bassiana (Hypocreales: Cordyciptaceae) Strain From Florida, USA.
AB - The horn fly, Haematobia irritans (L.) is an important cattle pest and
traditionally has been managed using insecticides; however, many horn fly
populations are insecticide-resistant in United States. Use of alternative
control techniques has been limited because of the challenges of managing a fly
pest on pastured cattle. After the discovery of a wild horn fly infected with
Beauveria bassiana in Florida, the fungus was cultured and evaluated for efficacy
against laboratory-reared horn flies. This fungal strain was selected for
increased virulence by passage through laboratory-reared horn fly hosts to
shorten interval from infection to fly death and subsequent conidia formation,
properties important to future use of the fungus as a biological control agent
against horn flies. After seven passages through horn fly hosts, fly mortality
was not significantly accelerated as evaluated through LT50 values, but conidia
were readily produced from these killed flies. Although further development is
needed to improve fungal efficacy, this fungal strain holds promise as a
biological control agent for inclusion in horn fly integrated pest management
programs.
PMID- 28423415
TI - The Potential Organ Involved in Cantharidin Biosynthesis in Epicauta chinensis
Laporte (Coleoptera: Meloidae).
AB - Cantharidin, a terpenoid defensive toxin mainly produced by blister beetles, is
among the most widely known insect natural products in the world. However, little
is known about the site of cantharidin biosynthesis in vivo. Our previous
research showed that 3-hydroxy-3-methylglutary-CoA reductase (HMGR) is an
essential enzyme in cantharidin biosynthesis. In this report, we further
investigated cantharidin titer and HMGR mRNA expression levels in different
tissues of male and female Epicauta chinensis, and performed a comparative
analysis of HMGR transcript levels in male Tenebrio molitor, a Tenebrionidae
beetle that cannot produce cantharidin. HMGR transcripts had a positive
correlation with cantharidin production. Furthermore, the specifically high
amounts of HMGR transcript and abundant cantharidin production in fat body of
male E. chinensis indicated the process of cantharidin synthesis may occur in the
fat body.
PMID- 28423416
TI - Beauveria bassiana (Ascomycota: Hypocreales) Introduced as an Endophyte in Corn
Plants and Its Effects on Consumption, Reproductive Capacity, and Food Preference
of Dichroplus maculipennis (Orthoptera: Acrididae: Melanoplinae).
AB - In this study, the effects of strain Beauveria bassiana (LPSC 1067) as an
endophyte in corn plants on consumption, fecundity, and food preference of
Dichroplus maculipennis were examined. We observed that the daily consumption by
grasshoppers fed with control plants was almost twice that of those that were fed
treated plants. Significant differences in fecundity of grasshoppers that were
fed with treated plants compared with those that only fed on control plants were
also observed. The number of eggs laid per female fed with control plants was
27.2, while the number of eggs laid per female that were fed during 15 d with
treated plants was 17.7. Similar results were observed when the number of
embryonated eggs was evaluated. The highest number of embryonated eggs were
recorded in those females that only fed on control plants (96%) while fewer
embryonated eggs were recorded in grasshoppers fed for 15 d with treated plants
only (25%). In relation to food preference the average consumption rate for D.
maculipennis females on control corn plants was 303.8 +/- 24.5 mg while it was
only 25 +/- 2.1 mg on plants treated with B. bassiana as an endophyte. In
summary, we observed that B. bassiana as a corn plant endophyte negatively
affected the daily consumption rate, fecundity and food preference of D.
maculipennis.
PMID- 28423417
TI - Multi-Species Mating Disruption in Cranberries (Ericales: Ericaceae): Early
Evidence Using a Flowable Emulsion.
AB - Pheromone-based mating disruption has proven to be a powerful pest management
tactic in many cropping systems. However, in the cranberry system, a viable
mating disruption program does not yet exist. There are commercially available
pheromones for several of the major pests of cranberries, including the cranberry
fruitworm, Acrobasis vaccinii Riley (Lepidoptera: Pyralidae) and blackheaded
fireworm, Rhopobota naevana (Hubner) (Lepidoptera: Tortricidae). Previous studies
have shown that mating disruption represents a promising approach for R. naevana
management although carrier and delivery technologies have remained unresolved.
The present study examined the suitability of Specialized Pheromone & Lure
Application Technology (SPLAT; ISCA Technologies, Inc., Riverside, CA), a
proprietary wax and oil blend, to serve as a pheromone carrier in the cranberry
system. In 2013 and 2014, we tested a blend of pheromones targeting A. vaccinii
and R. naevana in field-scale, replicated trials. Pheromones were loaded into
SPLAT and the resulting "SPLAT BFW CFW" formulation was deployed in commercial
cranberry marshes. We compared moth trap-catch counts within SPLAT-treated blocks
to those of conventionally managed blocks. In 2013, applications of SPLAT BFW CFW
resulted in highly successful disruption of R. naevana and promising, though
inconsistent, disruption of A. vaccinii. To improve disruption of A. vaccinii,
the pheromone load was increased in 2014, providing 92% and 74% reductions in
trap-catch for R. naevana and A. vaccinii, respectively. Importantly, larval
infestation rates in SPLAT-treated blocks were lower than those of conventionally
managed blocks. These results suggest that a multispecies mating disruption
system (SPLAT BFW CFW) may represent an effective pesticide-alternative for
serious pests of cranberries.
PMID- 28423418
TI - RNA-Seq Validation of RNAi Identifies Additional Gene Connectivity in Tribolium
castaneum (Coleoptera: Tenebrionidae).
AB - RNA interference (RNAi) is a functional genomics tool to correlate genotype and
phenotype by delivering targeted, gene-specific, and complementary dsRNA into a
host via injection, feeding, or other means in order to reduce gene expression.
In the red flour beetle, Tribolium castaneum, RNAi has been successful via
injected dsRNA at all life stages. Traditionally, successful transcript knockdown
has been quantified by qPCR on a gene-by-gene basis, where only expression of the
target gene and normalization genes are evaluated. In this study, RNA-Seq was
used to quantify transcript expression in larvae injected with dsRNA for
aspartate 1-decarboxylase (ADC), which gives a reliable phenotype of an adult
with a black cuticle instead of the wild-type red-brown. ANOVA of control, mock
injected, and ADC-dsRNA injected larvae indicated that target gene expression was
significantly (P = 0.002) reduced 4-fold, and the black phenotype was achieved in
all adults injected with ADC-dsRNA as larvae. In a pairwise analysis, significant
(P < 0.05) differential expression of other genes in ADC-injected larvae
suggested connections between gene pathways. One gene, dopamine receptor 2, was
increased in expression 227-fold (P = 0.025), presumably connected to previous
data that showed a reduction in expression of ADC results in increased levels of
dopamine. To evaluate the hypothesis that increased dopamine levels can affect
mobility, T. castaneum adults injected with ADC-dsRNA as larvae were
significantly impaired in movement tests compared to controls, similar to black
mutants in Drosophila melanogaster. The data demonstrate that RNA-Seq can reveal
gene connectivity and provide more complete data validation and analysis compared
to qPCR.
PMID- 28423419
TI - Temperature-Dependent Biological and Demographic Parameters of Coleomegilla
maculata (Coleoptera: Coccinellidae).
AB - Knowledge of the most suitable environmental conditions for an organism growth
and development is a prerequisite for developing mass rearing technology. The
temperature requirements for development and the optimal range of temperatures
for growth and reproduction of Coleomegilla maculata De Geer were studied. The
development time of individual C. maculata larvae was determined at 18, 21, 24,
27, 30, 33, and 36 degrees C. Development times were converted to development
rates and fitted to a nonlinear temperature-dependent model and to the linear day
degree model. Life and fertility table analysis was used to determine the optimal
temperature for population growth within a range of favorable temperatures
including 24, 25, 26, 27, and 28 degrees C. Nonlinear estimates of thermal
maximum (TM) for the postembryonic development of C. maculata was 35.09 +/- 10.35
degrees C. Estimation of TM based on pupal development was much lower at 27.23
+/- 1.52 degrees C. Linear and nonlinear estimates of low temperature
development threshold were 13.13 +/- and 4.77 +/- 3.03 degrees C for the whole
postembryonic development and 10.95 and 9.18 +/- 1.36 degrees C for the pupal
stage alone, respectively. The most favorable temperature for population growth
was 25 degrees C, where C. maculata showed significantly higher intrinsic rate
of increase (rm = 0.066) and significantly lower doubling time (10.57 d) than the
other favorable temperatures tested. A negative value of rm was obtained at 28
degrees C, indicating population decline occurring at this temperature making it
unfavorable for C. maculata.
PMID- 28423420
TI - Functional Response of Eretmocerus delhiensis on Trialeurodes vaporariorum by
Parasitism and Host Feeding.
AB - The parasitoid wasp, Eretmocerus delhiensis (Hymenoptera, Aphelinidae) is a
thelytokous and syn-ovigenic parasitoid. To evaluate E. delhiensis as a
biocontrol agent in greenhouse, the killing efficiency of this parasitoid by
parasitism and host-feeding, were studied. Killing efficiency can be compared by
estimation of functional response parameters. Laboratory experiments were
performed in controllable conditions to evaluate the functional response of E.
delhiensis at eight densities (2, 4, 8, 16, 32, 64, 100, and 120 third nymphal
stage) of Trialeurodes vaporariorum (Hemiptera, Aleyrodidae) on two hosts
including; tomato and prickly lettuce. The maximum likelihood estimates from
regression logistic analysis revealed type II functional response for two host
plants and the type of functional response was not affected by host plant.
Roger's model was used to fit the data. The attack rate (a) for E. delhiensis was
0.0286 and 0.0144 per hour on tomato and 0.0434 and 0.0170 per hour on prickly
lettuce for parasitism and host feeding, respectively. Furthermore, estimated
handling times (Th) were 0.4911 and 1.4453 h on tomato and 0.5713 and 1.5001 h on
prickly lettuce for parasitism and host feeding, respectively. Based on 95%
confidence interval, functional response parameters were significantly different
between the host plants solely in parasitism. Results of this study opens new
insight in the host parasitoid interactions, subsequently needs further
investigation before utilizing it for management and reduction of greenhouse
whitefly.
PMID- 28423421
TI - Efficacy of Some Wearable Devices Compared with Spray-On Insect Repellents for
the Yellow Fever Mosquito, Aedes aegypti (L.) (Diptera: Culicidae).
AB - The current Zika health crisis in the Americas has created an intense interest in
mosquito control methods and products. Mosquito vectors of Zika are of the genus
Aedes, mainly the yellow fever mosquito, Aedes aegypti. L. The use of repellents
to alter mosquito host seeking behavior is an effective method for the prevention
of mosquito-borne diseases. A large number of different spray-on repellents and
wearable repellent devices are commercially available. The efficacies of many
repellents are unknown. This study focuses on the efficacy of eleven different
repellents in reducing the number of Ae. aegypti female mosquitoes attracted to
human bait. We performed attraction-inhibition assays using a taxis cage in a
wind tunnel setting. One person was placed upwind of the taxis cage and the
mosquito movement towards or away from the person was recorded. The person was
treated with various spray-on repellents or equipped with different mosquito
repellent devices. We found that the spray-on repellents containing N,N-Diethyl
meta-toluamide and p-menthane-3,8-diol had the highest efficacy in repelling
mosquitoes compared to repellents with other ingredients. From the five wearable
devices that we tested, only the one that releases Metofluthrin significantly
reduced the numbers of attracted mosquitoes. The citronella candle had no effect.
We conclude that many of the products that we tested that were marketed as
repellents do not reduce mosquito attraction to humans.
PMID- 28423422
TI - Immunological Responses of Sesamia cretica to Ferula ovina Essential Oil.
AB - The current research was performed aiming to investigate the effects of Ferula
ovina essential oil on the fourth instar larval hemogram of Sesamia cretica. Four
main sorts of circulating hemocytes, including prohemocytes, plasmatocytes,
granulocytes (GRs), and oenocytoides, were identified in the fourth instar
larvae. Treatment of the larvae with the concentration of 1000 ppm of the
essential oil led to an enhancement of the total hemocyte and GR count followed
by a dose-dependent decrease at the concentrations of 2500 and 7000 ppm.
Plasmatocyte numbers declined in all the treatments with more significant effects
at increased doses. The greatest numbers of GRs, plasmatocytes, and total
hemocytes were found after 48 h of treatment. The highest phenol-oxidase activity
was recorded 12 h after treatment at the concentration of 2500 ppm. The highest
effect on nodule formation was exerted by the concentration of 7000 ppm 12 h
after treatment. The results of the present study clearly indicated that the
treatment of larvae by the essential oil of F. ovina decreased the numbers of
total and differential hemocyte counts although phenol-oxidase activity and the
number of nodules showed no decline in the treated larvae. These results
demonstrated that Ferula ovina essential oil has a significant effect on the
immune ability of the studied insect and can be useful and usable for future
research to practical management of this pest.
PMID- 28423423
TI - Invertebrates, Fungal Biomass, and Leaf Breakdown in Pools and Riffles of
Neotropical Streams.
AB - We evaluated fungal biomass (as ergosterol concentration) and invertebrate
colonization during leaf breakdown of Picramnia sellowii Planch. (Picramniaceae)
in pools and riffles of three low-order forested streams in southeastern Brazil.
We hypothesized that leaf breakdown will be higher in riffles due to the high
physical fragmentation and fungal activity. The experiment was carried out during
the dry season of 2012, using 108 litter bags, each containing 3 +/- 0.05 g of
air-dried leaves. After 7, 15, 30, 60, 90, and 120 d of incubation, six litter
bags (riffle = 3 and pool = 3) were removed from each stream. Leaf breakdown rate
(k) was classified as intermediate in pools and fast in riffles. We recorded
similar values of remaining leaf mass in two habitats until 60 d. However, at 90
and 120 d, this process was faster in riffles. The mean fungal biomass was
similar between habitats and showed an increase during the experiment at 90 d.
Fauna composition differed between habitats and across sampling dates, with
Chironomidae most contributing to these differences and being particularly
abundant in riffles and in the initial period of leaf breakdown (until 30 d).
Shredder abundance and biomass were not different between habitats and among
incubation durations. Leaf breakdown (remaining leaf mass) was positively
associated with fungal and shredder biomasses. However, water velocity was not
related to leaf breakdown. These findings emphasize the importance of fungal and
shredder organisms, as well as the low importance of water velocity, on mass loss
in low-order tropical streams.
PMID- 28423424
TI - Field Evaluation of Potential Pheromone Lures for Lygus lineolaris (Hemiptera:
Miridae) in the Mid-South.
AB - Plant bugs (Hemiptera: Miridae) are phytophagous pests of cultivated plants
around the world. In the mid-South region of the United States, Lygus lineolaris
(Palisot de Beauvois) is a primary pest of cotton, and causes economic damage.
Previously published research about the volatiles produced by members of the
genus Lygus, and other closely related groups, indicated that they produce blends
of hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-4-oxo-2-hexenal. Varying
ratios of the three compounds were loaded into pipette tips, and screened in
combination with non-UV white sticky cards for attractiveness to field
populations of L. lineolaris in Mississippi. Field screening indicated that a
lure expressing a ratio of 4:10:7 was the most effective at collecting L.
lineolaris, and collected similar numbers of individuals to those reported in
other studies using traps baited with live virgin insects over a similar period
of time. Availability of a synthetic pheromone usable in the climate of the mid
South will enable broader scale landscape level monitoring for populations of L.
lineolaris before movement into cotton fields and resulting economic damage.
PMID- 28423425
TI - Temporal Resource Partitioning and Interspecific Correlations in a Warm,
Temperate Climate Assemblage of Dung Beetles (Coleoptera: Scarabaeidae).
AB - Guilds of dung dwelling and tunneling dung beetles coexist in local assemblages
in warm temperate regions, despite the tendency of dwellers to be inferior
competitors. A field experiment on the Black Sea coast of Turkey examined the
role of temporal resource partitioning in their coexistence. Standardized dung
pads deposited at 4 h intervals through a 24 h period in summer were collected
12, 24, or 48 h later. Adults from 10 tunneling and seven dung dwelling species
were collected. The tunnelers contributed a high proportion of both total
abundance and biomass. There was a significant effect of dung deposition time and
exposure period on mean tunneler abundance. Mean tunneler abundance was nearly
seven times higher in dung deposited at 06:00 than at 18:00. The dwellers reduced
the potential for competitive interactions with tunnelers by relatively uniform
dispersal across the six dung deposition times. The distinctly different dung use
patterns by dwellers and tunnelers demonstrated temporal resource partitioning.
Interspecific correlation coefficients were also determined because interspecific
relationships are at the core of resource partitioning. Total tunneler and
dweller abundances were not correlated. Overall, there were strong positive
correlations between tunneling species and low correlations between tunneling and
dwelling species, and between dwelling species. The five most abundant tunnelers,
from two tribes and three genera, were strongly positively correlated. There were
substantial size differences among the four most abundant tunnelers that probably
facilitate their coexistence.
PMID- 28423426
TI - The Invasive Liriomyza huidobrensis (Diptera: Agromyzidae): Understanding Its
Pest Status and Management Globally.
AB - Liriomyza huidobrensis (Blanchard) is native to South America but has expanded
its range and invaded many regions of the world, primarily on flowers and to a
lesser extent on horticultural product shipments. As a result of initial invasion
into an area, damage caused is usually significant but not necessarily sustained.
Currently, it is an economic pest in selected native and invaded regions of the
world. Adults cause damage by puncturing abaxial and adaxial leaf surfaces for
feeding and egg laying sites. Larvae mine the leaf parenchyma tissues which can
lead to leaves drying and wilting. We have recorded 365 host plant species from
49 families and more than 106 parasitoid species. In a subset of the Argentinian
data, we found that parasitoid community composition attacking L. huidobrensis
differs significantly in cultivated and uncultivated plants. No such effect was
found at the world level, probably due to differences in collection methods in
the different references. We review the existing knowledge as a means of setting
the context for new and unpublished data. The main objective is to provide an
update of widely dispersed and until now unpublished data, evaluate dispersion of
the leafminer and management strategies in different regions of the world, and
highlight the need to consider the possible effects of climate change on further
regional invasions or expansions.
PMID- 28423427
TI - Influence of Temperature and Relative Humidity on the Insecticidal Efficacy of
Metarhizium anisopliae against Larvae of Ephestia kuehniella (Lepidoptera:
Pyralidae) on Wheat.
AB - A series of laboratory bioassays were conducted for the evaluation of the
insecticidal efficacy of an isolate of Metarhizium anisopliae (Metschnikoff)
Sorokin (Ascomycota: Hypocreales) against larvae of the Mediterranean flour moth,
Ephestia kuehniella Zeller (Lepidoptera: Pyralidae), under various temperature
relative humidity (r.h.) conditions. The fungus was applied at four doses (0, 8 *
106, 8 * 108, and 8 * 1010 conidia ml-1) on wheat and insect mortality was
assessed after exposure of 1, 2, 7, and 14 d. Bioassays were conducted at three
temperatures (20, 25, and 30 degrees C) and two r.h. levels (55 and 75%).
Although complete control was not achieved in any case, the fungus provided a
considerable level of insect control. Mortality of E. kuehniella larvae on wheat
treated with M. anisopliae ranged between 41.1 and 93.3% after 14 d of exposure,
whereas the respective mortality levels in control dishes never exceeded 28.3%.
The increase of temperature resulted in most cases to higher efficacy, indicating
that temperature is an important factor for the performance of the fungus. In
contrast, in most cases r.h. did not significantly affect the efficacy of the
fungus, at least for the humidity levels tested.
PMID- 28423428
TI - Aggregation Behavior and a Putative Aggregation Pheromone in Sugar Beet Root
Maggot Flies (Diptera: Ulidiidae).
AB - Male-biased aggregations of sugar beet root maggot, Tetanops myopaeformis (Roder)
(Diptera: Ulidiidae), flies were observed on utility poles near sugar beet (Beta
vulgaris L. [Chenopodiaceae]) fields in southern Idaho; this contrasts with the
approximately equal sex ratio typically observed within fields. Peak observation
of mating pairs coincided with peak diurnal abundance of flies. Volatiles
released by individual male and female flies were sampled from 08:00 to 24:00
hours in the laboratory using solid-phase microextraction and analyzed using gas
chromatography/mass spectrometry (GC/MS). Eleven compounds were uniquely detected
from males. Three of these compounds (2-undecanol, 2-decanol, and sec-nonyl
acetate) were detected in greater quantities during 12:00-24:00 hours than during
08:00-12:00 hours. The remaining eight compounds uniquely detected from males did
not exhibit temporal trends in release. Both sexes produced 2-nonanol, but males
produced substantially higher (ca. 80-fold) concentrations of this compound than
females, again peaking after 12:00 hours. The temporal synchrony among male
aggregation behavior, peak mating rates, and release of certain volatile
compounds by males suggest that T. myopaeformis flies exhibit lekking behavior
and produce an associated pheromone. Field assays using synthetic blends of the
putative aggregation pheromone showed evidence of attraction in both females and
males.
PMID- 28423429
TI - Modeling Temperature-Dependent Development of Glyphodes pyloalis (Lepidoptera:
Pyralidae).
AB - Development of Glyphodes pyloalis Walker was studied under laboratory conditions
at constant temperatures of 12, 16, 20, 24, 28, 30, 32, and 36 degrees C. No
development occurred at 36 degrees C. Although eggs hatched at 12 oC, no larvae
were capable of developing to adult stage. At 16 oC, survival rate was low (4%)
and prepupal stage lasted 101.68 +/- 11.03 d. Larvae completed development
through six stadia at 16, 30, and 32 degrees C. Developmental time of overall
immature stages varied from 46.62 d at 20 degrees C to 22.04 d at 30 degrees C
and increased at 32 degrees C. The lower temperature thresholds of 10.30 and
11.22 degrees C, and thermal constants of 429.18 and 401.88 DD were estimated by
traditional and Ikemoto-Takai linear models, respectively. The Tmin values
estimated by Analytis, Briere-2, Lactin-2, and Sharpe-Schoolfield-Ikemoto (SSI)
for overall immature stages were 12.40, 12.92, 9.00, and 13.04 degrees C,
respectively. The fastest development temperatures (Tfast) of 31.1, 31.1, 30.8,
and 30.7 degrees C were estimated for overall immature stages based on Analytis,
Briere-2, Lactin-2, and SSI, respectively. The intrinsic optimum temperature
(Topt) estimated from the thermodynamic SSI model for total developmental time
was 24.63 degrees C, in which the maximal active state enzymes involved in
developmental process. The nonlinear models of Analytis, Lactin-2, Briere-2, and
SSI estimated the upper temperature thresholds (Tmax) at 36.66, 35.97, 38.88, and
34.05 degrees C, respectively. These findings could be used to predict the
population dynamics of G. pyloalis for an effective management.
PMID- 28423430
TI - Bioactivity of Novel Botanical Insecticide From Gnidia kaussiana (Thymeleaceae)
Against Callosobruchus maculatus (Coleoptera: Chrysomelidae) in Stored Vigna
subterranea (Fabaceae) Grains.
AB - Hexane, acetone, and methanol extracts from Gnidia kaussiana Meisn
(Thymeleaceae), each at two dosages (0.2 and 1 ml/50 g grains corresponding,
respectively to 1 and 5g/kg), and neem seed oil (NSO), used as standard
insecticide were evaluated for repellence, toxicity to Callosobruchus maculatus
(F.) (Coleoptera: Chrysomelidae) adults, F1 progeny inhibition, persistence and
as grain protectant during storage. Experiments were laid out at complete
randomized design with five replications for repellence test and four for others.
All the extracts were effective in protecting stored Bambara groundnut (Vigna
subterranea (L.) Verdcourt) from insect attack; however, their bioactivities were
inversely correlated with solvent polarity. No adult survival was recorded in
treated grains with hexane extract at 5 g/kg dosage within 2 d exposure. Also at
5 g/kg, all extracts hindered adults emergence, grain damage and weight loss
after 4 months storage. Moreover, hexane extract was more repellent and exhibited
averagely repellency. The insecticidal effectiveness of hexane extract did not
decreased provided that the exposure time of insects to the product was high (7
d). The potency of acetone and methanol extracts decreased with storage time,
although not linearly and remained significantly toxic to C. maculatus up to 60 d
of storage. Therefore, hexane and acetone extracts are good candidates for
incorporation in integrated pest management programs for control of cowpea
weevils in stored grains by poor-resourced farmers and store keepers in Cameroon
and other developing countries.
PMID- 28423431
TI - [Treatment and Secondary Prevention of Venous Thromboembolism - Change in Oral
Anticoagulation].
AB - With the recent approval of the fourth direct non vitamin K dependent oral
anticoagulant (NOAC) edoxaban the range of available NOACs for the treatment of
venous thromboembolism (VTE) has expanded. Shortly thereafter, two updated
guidelines for the prevention and treatment of VTE have been published. In these
NOACs are listed as equal anticoagulants to low-molecular weight heparin (LMWH),
or fondaparinux (FDX), and VKA for the initial or maintenance treatment of VTE.
All NOACs are approved for the maintenance therapy after VTE and two NOACs
(rivaroxaban and apixaban) for the initial treatment in addition in an increased
dose.NOACs differ in their pharmacodynamic and pharmacokinetic properties. In
patients with renal insufficiency the dose of all NOACs should be reduced
similarly to NMH/FDX. In contrast to VKAs, bridging with NOACs in case of
surgical interventions is generally dispensable. Similar to NMHs or FPX renal
function and individual bleeding risk dependent dose intermission is generally
sufficient. Conventional coagulation parameters like aPTT and INR are not
suitable for the monitoring of NOACs. Only in seldom cases, laboratory monitoring
with use of adjusted anti-Xa testing or diluted thrombin time (dabigatran) may be
helpful.
PMID- 28423432
TI - [Clinical and pathological prognostic factors for the long-term survival of
patients with pT1 renal cell carcinoma].
AB - Introduction The incidence of renal cell carcinoma (RCC) has been increasing over
the past few decades. Simultaneously, due to improved imaging, small renal masses
at stage pT1 have been diagnosed more frequently. However, it is known that even
small RCCs may recur and metastasize at a late point of time. This study aimed to
identify easy-to-assess clinical and histopathological prognostic markers for
long-term survival. Patients/Methods We performed a retrospective analysis of
patients who underwent surgical treatment of a pT1 RCC in a single centre between
1993 and 2007. The prognostic impact of clinical and histopathological parameters
was investigated regarding recurrence-free survival (RFS), cancer-specific
survival (CSS) and overall survival (OS). Univariate Kaplan-Meier analysis and
multivariate Cox regression analysis were performed using SPSS 23. Results
Overall, 571 patients were included with a median follow-up of 111 months.
Univariate analysis revealed that higher grading (p = 0.031) and stage pT1b (p <
0.001) were statistically significantly associated with worse RFS. Likewise,
stage pT1b (p = 0.001) and grading G2/3 (p = 0.019) were significantly associated
with shorter CSS. Multivariate analysis revealed that stage pT1b was the only
predictor for reduced RFS (p = 0.001) and CSS (p = 0.009). Total nephrectomy (p =
0.024), and diabetes (p < 0.001) were significantly associated with reduced OS.
Multivariate analysis revealed that multifocal tumours (p = 0.041) and diabetes
(p < 0.001) were the best predictive factors for OS. Conclusion The identified
prognostic parameters may help to provide a risk-adapted after follow-up for
patients with small renal tumours.
PMID- 28423433
TI - [Myositis Ossificans Traumatica in the Craniocervical Junction: A Case Report and
Review of Literature].
AB - Background Myosits ossificans (MO) is a rare but important differential diagnosis
for a heterotrophic bony tumor in the muscles. It is often misdiagnosed as a
malignant tumor. With a previous trauma the diagnosis is myositis ossificans
traumatic (MOT). In most cases, it is benign and predominantly seen in the big
muscles. But there can be malignant etiologies too. Case Description We report a
rare case of MO in the muscle of the craniocervical junction. This 37-year-old
woman had a riding accident years ago. Because of persisting pain and cervical
dysfunction, we did a total resection. Clinical Implications MOT is a benign
tumor that can be treated conservative in most cases. In case of persistent pain
or neurological deficits, and especially for securing diagnosis, surgical
resection is recommended.
PMID- 28423434
TI - [Radiologic Presentation in Subspine Impingement and Correlation with
Intraarticular Impingement in the Hip].
AB - Background Besides the known intraarticular femoroacetabular impingement (FAI),
recently forms of extra-articular impingement of the hip have been increasingly
recognized. Recent studies have described an extra-articular impingement between
a distal extension of the anterior inferior iliac spine (AIIS) and the femoral
neck (AIIS or subspine impingement). Evidently, an association between this
subspine impingement and an intraarticular FAI seems to exist. Little is known
about the incidence of this impingement type and the value of its radiological
diagnostics. The aim of this study was therefore to evaluate the correlation of a
subspine impingement with intraarticular femoroacetabular impingement and
radiological criteria of subspine impingement. Material and Methods In 2013
arthroscopic correction of intra-articular femoroacetabular impingement was
performed in 80 cases. This collective was evaluated for simultaneous
intraoperative findings of subspine impingement. In addition, the patients were
evaluated for radiological signs of subspine impingement in conventional X-ray. A
projection of the AIIS either below the acetabular sourcil or the anterior
acetabular rim in an AP pelvis X-ray was considered as a radiological sign of low
AIIS formation. These radiological findings were compared with the presence of
intraoperative signs for subspine impingement, which are defined as a combination
of focal capsule synovitis, labral ecchymosis close to the AIIS and a decreased
offset between the acetabular rim and the AIIS. The specificity and sensitivity
of the pre-operative radiological signs were calculated. Results A subspine
impingement was found in 17 cases (21 %, 3 female, 14 male, mean age 28 years). A
projection of the AIIS caudal to the acetabular sourcil in the AP pelvis X-ray
was represented in 15 of the 17 cases detected (sensitivity 0.90, specificity
0.88). A projection below the anterior glenoid rim was detectable in 2 cases with
symptomatic AIIS impingement (sensitivity 0.12, specificity 1). Conclusion A
relevant proportion of patients with intraarticular FAI showed intraoperative
signs for an additive extraarticular AIIS impingement. Preoperative pelvic X-rays
are helpful with a sensitivity of 90 % in detecting the presence of a distal
extension of the AIIS in FAI patients. Evaluation of the preoperative AP pelvis x
ray should include the projection of the AIIS. We recommend evaluation for
subspine impingement during routine arthroscopy.
PMID- 28423435
TI - [Pathogen Spectrum of Complex Wounds in Germany from War Zones].
AB - Background Treatment of the injured from war zones with wounds with multi
resistant pathogens is becoming more common in Germany, especially in German
Armed Forces Hospitals. In most cases, the pre-treatment of these patients has
been inadequate and they have a high load of rare pathogens. In Germany,
hospitals have to evaluate these pathogens by law. The aim of this study was to
review current German guidelines and data on the array of pathogens of complex
trauma wounds in Germany and to compare patients with wounds and multi-resistant
pathogens from war zones treated in Germany. Patients and Methods A PubMed search
was performed on all multiresistant pathogens, antibiotic resistance and
guidelines in Germany from 2005 to 2015. The databases and recommendations of the
Robert Koch Institute, the Paul Ehrlich Society and the National Reference Centre
for the Surveillance of Nosocomial Infections were analysed. The screening
results of injured patients from war zones treated in the German Armed Forces
Hospital Ulm were included. Results The array of pathogens for nosocomial
infections has not changed, but the ratios of the pathogens has altered.
Methicilin-resistant Staphylococcus aureus (MRSA) has decreased, but vancomycin
resistant enterococci have increased continuously. Enterococcus faecium (E.
faecium) now make up the largest fraction of VRE. The databases do not yet
provide data on the relatively new classification of multiresistant gramnegative
(MRGN) pathogens. MRGN pathogens play the main role in injured patients from war
zones. Conclusion In the last ten years, there have been changes in the
resistance and ratios of multi-resistant pathogens. MRSA has decreased over the
last ten years, but reserve antibiotics are increasingly needed. VRE are
increasing and even some reserve antibiotics have lost their efficacy because of
the use of modern antibiotics. There are not yet any German datasets available on
3- and 4-MRGN. These pathogens play the main role in injured patients from war
zones treated in Germany: it is crucial to perform routine screening and to take
all precautions, including isolation. Surgical wound therapy is of increasing
importance and uncritical and expensive antibiotic therapy is becoming becomes
less important.
PMID- 28423436
TI - ?
PMID- 28423437
TI - [Expert Assessment of Traumatic Disc Herniations].
AB - In numerous legal areas, expert assessments are needed to clarify the causality
of herniated discs: Was the damage caused by an accident? The literature mentions
specific requirements regarding the trauma mechanism as well as temporal
criteria, which prescribe the causality test. These are essentially high-energy
traumas with immediate functional impairments. Accident-related MRI examinations
are of paramount importance in the expert assessment process to confirm the
primary body harm. In examining the causality constituting liability, competitive
causes must be assessed. Since the legal requirements of the causality test
differ in civil and social law, legal norms need to be taken into account. We
present a test scheme that supports the assessment process through entry,
implementation and decision-making levels.
PMID- 28423438
TI - [Integration of Injured Hands].
AB - : Any injury of a hand more or less disintegrates the injured hand. The
rehabilitation of an alienated hand is prolonged. How can the alienation of the
own but injured hand and the involuntary and unconscious inhibition of its
perception and use be diagnosed, explained, avoided and designated? Medical
observations and interviews with patients and therapists on the occasion of
rehabilitation of hand injuries resulted in the development of a new concept of
biopsychosocial integrating rehabilitation and a creative hand therapy with the
objective of integrating injured and alienated hands. DIAGNOSIS: The inhibition
of the gesture of thinking has been the most revealing sign for the diagnosis of
a disintegration of an injured hand. Explanation: The involuntary inhibition to
recognize and use an injured hand causes and implicates the alienation of the
rested hand. PREVENTION: Information by hand surgeons and hand therapists.
Creative hand therapy guides the attention to complex and pleasing activities. In
complex disintegrations after hand injuries the hand as well as the person need
help. Designation: Hypotheses: Posttraumatic Proportionate Regional
Disintegration while the tissues heal. Posttraumatic Complex Regional
Disintegration, if the disintegration overruns the healing of tissues or if the
person suffers. The Complex Regional Pain Syndrome is distinguished as a rare
exception of a biopsychosocial disintegration. Posttraumatic regional
disintegration seems to be proportionate while the tissues are healing. If the
mentioned sensations of the patients and the visible signs of disintegration
persist, the disorder spreads onto the biopsychosocial unit of the person. This
disorder of hand and person may be designated as a complex disorder. The impact
of a proportionate posttraumatic disintegration as well as the formation and
exacerbation of a complex posttraumatic disintegration may be prevented by the
facilitation of the integration of an injured hand. Scientific prove is needed
for: the guiding impact of the healthy hand for physiotherapy; the impact of the
gesture of thinking to diagnosis and treatment of disintegrations; the
effectivity and the economic efficiency of a biowpsychosocial integrating
rehabilitation and creative hand therapy.
PMID- 28423439
TI - [Reliable Flaps for Congenitally Malformed Hands].
AB - Congenital hand malformations are rare, but hand function and aesthetics cannot
be improved by surgery in every affected child. However, whenever this is
possible, it is important to create an individual surgical plan for each child.
Growth has to be taken into account in the accurate planning of incisions and
local flaps. Just because it is technically possible, not every flap should be
used in the malformed child's hand. In the following article, we present a
collection of reliable flaps in the surgery of the congenitally malformed hand.
PMID- 28423440
TI - [Results After Distal Digital Replantation - Is It Worth The Effort?]
AB - There are only relative indications for distal digital replantation in zones 1
and 2 according to Tamai. In contrast to primary closure for fingertip
amputations, replantation is a complex procedure that requires skills in
supermicrosurgical techniques, as vessels with diameters between 0.3-0.8 mm are
connected. In addition the time spent in hospital and the time off from work are
longer. Distal digital replantation is thus only indicated, if the expected
functional and aesthetic benefits surmount those of primary closure. We
retrospectively analysed all fingertip amputations in zone 1 and 2 according to
Tamai between 9/2009 and 7/2014 where we attempted distal digital replantation.
The success of replantation, wound healing and functional results were evaluated
according to Yamano. We performed 11 distal digital replantations in the study
period. There were 6 total amputations, 4 subtotal amputations and 1 avulsion of
the digital pulp. Revascularisation with long-term reattachment of the amputated
tissues was possible in 8 cases (73%). In 3 cases (27%) secondary amputation
closure was necessary. The mean operating time was 3 h 56 min. 6 patients, which
had a successful replantation, were available for follow-up examinations after a
mean period of 19 months. 5 patients were satisfied with the result and would
again prefer replantation over primary amputation closure. 4 patients reported a
good function of the replanted digits and did not complain about any limitations
in their use. 2 patients complained about restricted function. All patients could
return to their previous places of employment and were free of pain. Of the 12
affected digital nerves 11 nerves had a 2-point discrimination (2-PD) of <=15 mm,
3 of them had a 2-PD between 7 and 10 mm and 4 of them of <6 mm. Soft tissue
atrophy was obvious in 3 replanted digits and nail deformities in 2 patients.
Distal digital replantation is complex and technically challenging. It leads to
high patient satisfaction with only minimal functional limitations, if
successful. Due to the good results that can be obtained by these procedures,
fingertip replantation should be attempted, if operative risks are minimal and if
requested by the patient.
PMID- 28423441
TI - [Thumb Lengthening Following Amputation at the Proximal Phalanx using a
Semicircular Distraction Ring Fixator: Results of 5 Cases].
AB - Traumatic amputation of the thumb at the proximal phalanx or the
metacarpophalangeal joint can be treated by distraction lengthening depending on
the location of the amputation, the patient's age, occupation and functional
demands. We report the results of proximal phalanx lengthening in 5 patients
using a semicircular ring-type external fixator device. This prototype was
developed at our clinic in collaboration with a specialised small company
(Rotomed AG, Allmenstrasse 4, CH-4512 Bellach, www.rotomed.ch) based on the
principles of Ilizarov's external fixator. In all patients, subjective and
objective results were satisfactory (26.2 mm distraction length and an average
Michigan Hand Outcome Score of 82.2%) without any rotational/axial deformities or
complications requiring revision surgery.
PMID- 28423442
TI - [Atypical Lipomatous Tumour of the Hand].
AB - Atypical lipomatous tumours (ALT) are rare semi-malignant adipose tissue tumours
with the potential to transform into sarcomas. They may occur throughout the
body, although the hands are very rarely involved. We present the case of a 49
year-old man with a lipomatous tumour measuring 8*4 cm at the dorsum of the right
thumb. MRI demonstrated an inhomogeneous signal after contrast medium
application. The tumour was excised in its entirety. Since histology confirmed
the diagnosis of an ALT, the thumb was irradiated. The patient remained free of
recurrence. An ALT has to be suspected if a lipomatous tumour is very large. We
recommend an MRI prior to surgery in tumours larger than 5 cm. Excision should
follow oncologic principles.
PMID- 28423443
TI - [The Extended Percutaneous Needle Fasciotomy Technique (PNF+) For Dupuytren's
Contracture].
AB - The extended percutaneous needle fasciotomy (PNF+) is a minimal invasive
technique especially suitable for treating severe Dupuytren's contractures and
recurrences. The familiar needle fasciotomy is complemented by a spontaneous
tearing of the skin and a full-thickness graft to cover the defect. Skin tears in
fingers and palm are not a complication, but an integral part of the PNF+. The
neurovascular bundles remain intact. This surgical procedure may be repeated as
often as required.
PMID- 28423444
TI - [Comment on "The Technique of Enhanced Percutaneous Needle Fasciotomy (PNF+) for
Dupuytren's Contracture"].
PMID- 28423445
TI - [Comment on the Case Report "Atypical Lipomatous Tumour of the Hand"].
PMID- 28423446
TI - [Dorsal Dislocation of the Os Trapezoideum: A Case Report].
PMID- 28423447
TI - [Type I Trichorhinophalangeal Syndrome - Rare, but Catchy].
PMID- 28423448
TI - ?
PMID- 28423449
TI - ?
PMID- 28423450
TI - ?
PMID- 28423451
TI - [Salvage Procedure after Trapeziectomy using Mini TightRope(r)].
PMID- 28423453
TI - Periodontal treatment in private dental practice: a case-based survey.
AB - BACKGROUND: This study aimed to assess the management and referral patterns of
Victorian general dental practitioners based on periodontal diagnosis. METHODS:
Following ethics approval, Victorian general dental practitioners were invited to
complete five randomized text-based periodontitis scenario questionnaires. Based
on their diagnosis, respondents were asked for their management options and asked
to specify who would perform these treatments. Respondents were also asked about
referral procedures. RESULTS: One hundred and thirty-five dentists attempted the
survey. Most were in group practice and based in Melbourne. Of the total
respondents, 22.5% worked in a practice employing a hygienist. The management of
periodontal disease was appropriate, and treatment options increased with
severity. As severity increased, patients were more likely to be referred to a
periodontist. Periodontal services referred by general dentists to dental
hygienists increased with the number of days the hygienists worked within a
practice. Over- and underdiagnosis did not markedly affect management. The
recommendation of antibiotics, mouthwashes and periodontal surgery varied
depending on year and school of graduation. CONCLUSIONS: The general dentists
that completed the survey are managing periodontal conditions appropriately and
according to current guidelines.
PMID- 28423454
TI - UK NEQAS survey of allergen component testing across the United Kingdom and other
European countries.
AB - The clinical utility of molecular diagnostic approaches in allergy investigation
is being recognized increasingly to play a significant role in the management of
allergic patients. Determining the sensitization pattern, which is best achieved
through the use of component resolved diagnostics (CRD), allows effective risk
stratification, appropriate treatment and patient selection for immunotherapy. In
order to assess the diagnostic service provisions for in-vitro allergy testing
across Europe, a survey was carried out via the total immunoglobulin (Ig)E and
specific IgE external quality assurance schemes run by UK National External
Quality Assessment Service (NEQAS) Immunology, Immunochemistry and Allergy. This
survey assessed allergy testing, and in particular allergen components offered by
the laboratories, and found a wide variability in service provision, particularly
between the United Kingdom and other European Union (EU) countries. Furthermore,
there was lack of standardization for acquisition of clinical information to aid
allergen (and component) selection, gating strategy, testing algorithms and
clinical interpretation. Interestingly, a significant proportion of laboratories
(the majority from EU) stated that they 'used' the results for peanut components
for risk stratification. However, the vast majority of participants were unaware
of guidelines relating to the use of allergen component testing, and agreed that
further education would assist in reaching a common platform. Hence, this survey
has highlighted that although CRD has been adopted into routine diagnostics
across Europe, it is potentially compromised by lack of standardized protocols
and guidance sources. Consequently, there is a need for local or national
standards and education through External Quality Assurance services on the
performance and application of CRD into allergy investigation.
PMID- 28423455
TI - Simulation and curriculum design: a global survey in dental education.
AB - BACKGROUND: Curriculum reforms are being driven by globalization and
international standardization. Although new information technologies such as
dental haptic virtual reality (VR) simulation systems have provided potential new
possibilities for clinical learning in dental curricula, infusion into curricula
requires careful planning. METHODS: This study aimed to identify current patterns
in the role and integration of simulation in dental degree curricula
internationally. An original internet survey was distributed by invitation to
clinical curriculum leaders in dental schools in Asia, Europe, North America, and
Oceania (Australia and New Zealand). RESULTS: The results (N = 62) showed Asia,
Europe and Oceania tended towards integrated curriculum designs with North
America having a higher proportion of traditional curricula. North America had
limited implementation of haptic VR simulation technology but reported the
highest number of scheduled simulation hours. Australia and New Zealand were the
most likely regions to incorporate haptic VR simulation technology. CONCLUSIONS:
This survey indicated considerable variation in curriculum structure with
regionally-specific preferences being evident in terms of curriculum structure,
teaching philosophies and motivation for incorporation of VR haptic simulation
into curricula. This study illustrates the need for an improved evidence base on
dental simulations to inform curriculum designs and psychomotor skill learning in
dentistry.
PMID- 28423456
TI - Progesterone resistance in endometriosis: origins, consequences and
interventions.
AB - Endometriosis is a common cause of pelvic pain and affects up to 10% of women of
reproductive age. Aberrant progesterone signaling in the endometrium plays a
significant role in impaired decidualization and establishment of ectopic
endometrial implants. Eutopic endometrial cells from women with endometriosis
fail to downregulate genes needed for decidualization, such as those involved in
cell cycle regulation, leading to unbridled proliferation. Several causes of
progesterone resistance in the endometrium have been postulated, including
congenital "preconditioning", whereby the in utero environment renders infants
susceptible to neonatal uterine bleeding and endometriosis. Progesterone action
is crucial to decreasing inflammation in the endometrium, and deviant
progesterone signaling results in a proinflammatory phenotype. Conversely,
chronic inflammation can induce a progesterone-resistant state. Repetitive
retrograde endometrial shedding begets chronic peritoneal inflammation, which
further exacerbates progesterone resistance. Genetic causes of progesterone
resistance include progesterone receptor gene polymorphisms, altered microRNA
expression, and epigenetic modifications to progesterone receptors and their
targets. Environmental toxins such as dioxin play a possible role in the genesis
of endometriosis by permitting an inflammatory milieu. A consequence of impaired
progesterone action is that hormonal therapy is rendered ineffective for a subset
of women with endometriosis. Synthetic progestins, such as dienogest, may
overcome this phenomenon by increasing progesterone receptor expression and
decreasing proinflammatory cytokines. Other modalities include high dose depot
formulations of progestins, medicated intrauterine devices and the likely advent
of oral GnRH antagonists. Unearthing root causes of progesterone inaction in
endometriosis will aid in the development of novel therapeutics geared toward
prevention and treatment.
PMID- 28423457
TI - Use of Online Health Information by Geriatric and Adult Emergency Department
Patients: Access, Understanding, and Trust.
AB - OBJECTIVE: The objective was to characterize geriatric patients' use of online
health information (OHI) relative to younger adults and assess their comfort ith
OHI compared to health information (HI) from their physician. METHODS: This was a
prospective cross-sectional survey study of adult emergency department (ED)
patients. The survey assessed patients' self-reported use of OHI in the past year
and immediately prior to ED visit and analyzed differences across four age
groups: 18-39, 40-64, 65-74, and 75+. Patients' ability to access, understand,
and trust OHI was assessed using a 7-point Likert scale and compared to parallel
questions regarding HI obtained from their doctor. Patient use of OHI was
compared across age groups. Comfort with OHI and HI obtained from a doctor was
compared across age groups using the Kruskal-Wallis test. Comparisons between
sources of HI were made within age groups using the Wilcoxon signed-rank test.
RESULTS: Of 889 patients who were approached for study inclusion, 723 patients
(81.3%) completed the survey. The majority of patients had used OHI in the past
year in all age groups, but older patients were less likely to have used OHI: age
18-39, 90.3%; 40-64, 85.3%; 65-74, 76.4%; and 75+, 50.7% (p < 0.001). The
youngest patients were most likely to have used OHI prior to coming to the ED,
47.1%, 28.3%, 17.1%, and 8.0% (p < 0.001). Older patients were more likely to
have an established doctor-18-39, 79.4%; 40-64, 91.1%; 65-74, 97.5%; and 75+
97.4% (p < 0.001)-and were more likely to have contacted their doctor prior to
their ED visit: 36.7, 40.2, 46.7, and 53.5% (p = 0.02). The oldest patients were
most likely to find HI more accessible from their doctor than the Internet, while
the youngest patients found HI more accessible on the Internet than from their
doctor. Regardless of age, patients noted that information from their physician
was both easier to understand and more trustworthy than information found on the
Internet. CONCLUSION: Although many older patients used OHI, they were less
likely than younger adults to use the Internet immediately prior to an ED visit.
Despite often using OHI, patients of all age groups found healthcare information
from their doctor easier to understand and more trustworthy than information from
the Internet. As health systems work to efficiently provide information to
patients, addressing these perceived deficiencies may be necessary to build
effective OHI programs.
PMID- 28423458
TI - Dissecting virulence function from recognition: cell death suppression in
Nicotiana benthamiana by XopQ/HopQ1-family effectors relies on EDS1-dependent
immunity.
AB - Many Gram-negative plant pathogenic bacteria express effector proteins of the
XopQ/HopQ1 family which are translocated into plant cells via the type III
secretion system during infection. In Nicotiana benthamiana, recognition of
XopQ/HopQ1 proteins induces an effector-triggered immunity (ETI) reaction which
is not associated with strong cell death but renders plants immune against
Pseudomonas syringae and Xanthomonas campestris pv. vesicatoria strains.
Additionally, XopQ suppresses cell death in N. benthamiana when transiently co
expressed with cell death inducers. Here, we show that representative XopQ/HopQ1
proteins are recognized similarly, likely by a single resistance protein of the
TIR-NB-LRR class. Extensive analysis of XopQ derivatives indicates the
recognition of structural features. We performed Agrobacterium-mediated protein
expression experiments in wild-type and EDS1-deficient (eds1) N. benthamiana
leaves, not recognizing XopQ/HopQ1. XopQ recognition limits multiplication of
Agrobacterium and attenuates levels of transiently expressed proteins.
Remarkably, XopQ fails to suppress cell death reactions induced by different
effectors in eds1 plants. We conclude that XopQ-mediated cell death suppression
in N. benthamiana is due to the attenuation of Agrobacterium-mediated protein
expression rather than the cause of the genuine XopQ virulence activity. Thus,
our study expands our understanding of XopQ recognition and function, and also
challenges the commonly used co-expression assays for elucidation of in planta
effector activities, at least under conditions of ETI induction.
PMID- 28423459
TI - Breaks in MODIS time series portend vegetation change: verification using long
term data in an arid grassland ecosystem.
AB - Frequency and severity of extreme climatic events are forecast to increase in the
21st century. Predicting how managed ecosystems may respond to climatic extremes
is intensified by uncertainty associated with knowing when, where, and how long
effects of extreme events will be manifest in an ecosystem. In water-limited
ecosystems with high inter-annual variability in rainfall, it is important to be
able to distinguish responses that result from seasonal fluctuations in rainfall
from long-term directional increases or decreases in precipitation. A tool that
successfully distinguishes seasonal from directional biomass responses would
allow land managers to make informed decisions about prioritizing mitigation
strategies, allocating human resource monitoring efforts, and mobilizing
resources to withstand extreme climatic events. We leveraged long-term
observations (2000-2013) of quadrat-level plant biomass at multiple locations
across a semiarid landscape in southern New Mexico to verify the use of
Normalized Difference Vegetation Index (NDVI) time series derived from 250-m
Moderate Resolution Imaging Spectroradiometer (MODIS) data as a proxy for changes
in aboveground productivity. This period encompassed years of sustained drought
(2000-2003) and record-breaking high rainfall (2006 and 2008) followed by
subsequent drought years (2011 through 2013) that resulted in a restructuring of
plant community composition in some locations. Our objective was to decompose
vegetation patterns derived from MODIS NDVI over this period into contributions
from (1) the long-term trend, (2) seasonal cycle, and (3) unexplained variance
using the Breaks for Additive Season and Trend (BFAST) model. BFAST breakpoints
in NDVI trend and seasonal components were verified with field-estimated biomass
at 15 sites that differed in species richness, vegetation cover, and soil
properties. We found that 34 of 45 breaks in NDVI trend reflected large changes
in mean biomass and 16 of 19 seasonal breaks accompanied changes in the
contribution to biomass by perennial and/or annual grasses. The BFAST method
using satellite imagery proved useful for detecting previously reported ground
based changes in vegetation in this arid ecosystem. We demonstrate that time
series analysis of NDVI data holds potential for monitoring landscape condition
in arid ecosystems at the large spatial scales needed to differentiate responses
to a changing climate from responses to seasonal variability in rainfall.
PMID- 28423461
TI - Attributes of the complete dental record: a Delphi approach to standards.
AB - BACKGROUND: Adherence to the Dental Board of Australia Guidelines on dental
records is not universal and remediation of deficient practise requires clarity
in the practical application of standards. The aim of this research is to clarify
practical requirements of dental record keeping in New South Wales. METHODS:
Seventeen experts were invited to participate in an electronically administered
series of Delphi questionnaires. Concepts were refined until consensus was
reached. RESULTS: Two rounds were required to achieve a satisfactory level of
consensus (>80%). A high level of consensus was obtained across the two rounds,
with 72% and 86% agreement on propositions in the first and second rounds,
respectively. Consensus criteria were established in 14 domains to establish
attributes of the complete dental record (ACDR). CONCLUSIONS: The ACDR may
supplement existing national guidelines and are likely to be useful in a
remediation context in which clear, unambiguous expectations for conduct are
paramount.
PMID- 28423460
TI - Individual and Neighborhood Characteristics of Children Seeking Emergency
Department Care for Firearm Injuries Within the PECARN Network.
AB - OBJECTIVE: The objective was to describe the characteristics of children seeking
emergency care for firearm injuries within the PECARN network and assess the
influence of both individual and neighborhood factors on firearm-related injury
risk. METHODS: This was a retrospective, multicenter cross-sectional analysis of
children (<19 years old) presenting to 16 pediatric EDs (2004-2008). ICD-9-CM E
codes were used to identify and categorize firearm injuries by mechanism/intent.
Neighborhood variables were derived from home address data. Multivariable
analysis examined the influence of individual and neighborhood factors on firearm
related injuries compared to nonfirearm ED visits. Injury recidivism was
assessed. RESULTS: A total of 1,758 pediatric ED visits for firearm-related
injuries were analyzed. Assault (51.4%, n = 904) and unintentional injury (33.2%,
n = 584) were the most common injury mechanisms. Among children with firearm
injuries, 68.3% were older adolescents (15-19 years old), 82.3% were male, 68.2%
were African American, and 76.3% received public insurance/were uninsured.
Extremity injuries were most common (75.9%), with 20% sustaining injuries to
multiple body regions, 48.1% requiring admission and 1% ED mortality.
Multivariable analysis identified firearm injury risk factors, including
adolescent age (p < 0.001), male sex (p < 0.001), non-Caucasian race/ethnicity (p
< 0.001), public payer/uninsured status (p < 0.001), and higher levels of
neighborhood disadvantage (p < 0.001). Among children with firearm injuries, 12
month ED recidivism for any reason was 22.4%, with < 1% returning for another
firearm injury. CONCLUSION: Among children receiving ED treatment within the
PECARN network, there are distinct demographic and neighborhood factors
associated with firearm injuries. Among younger children (<10 years old),
unintentional injuries predominate, while assault-type injuries were most common
among older adolescents. Overall, among this PECARN patient population, male
adolescents living in neighborhoods characterized by high levels of concentrated
disadvantage had an elevated risk for firearm injury. Public health efforts
should focus on developing and implementing initiatives addressing risk factors
at both the individual and the community level, including ED-based interventions
to reduce the risk for firearm injuries among high-risk pediatric populations.
PMID- 28423462
TI - Geochemical signatures of benthic foraminiferal shells from a heat-polluted
shallow marine environment provide field evidence for growth and calcification
under extreme warmth.
AB - Shallow marine calcifiers play an important role as marine ecosystem engineers
and in the global carbon cycle. Understanding their response to warming is
essential to evaluate the fate of marine ecosystems under global change
scenarios. A rare opportunity to test the effect of warming acting on natural
ecosystems is by investigation of heat-polluted areas. Here, we study growth and
calcification in benthic foraminifera that inhabit a thermally polluted coastal
area in Israel, where they are exposed to elevated temperatures reaching up to
~42 degrees C in summer. Live specimens of two known heat-tolerant species
Lachlanella sp. 1 and Pararotalia calcariformata were collected over a period of
1 year from two stations, representing thermally polluted and undisturbed
(control) shallow hard bottom habitats. Single-chamber element ratios of these
specimens were obtained using laser ablation, and the Mg/Ca of the most recently
grown final chambers were used to calculate their calcification temperatures. Our
results provide the first direct field evidence that these foraminifera species
not only persist at extreme warm temperatures but continue to calcify and grow.
Species-specific Mg/Ca thermometry indicates that P. calcariformata precipitate
their shells at temperatures as high as 40 degrees C and Lachlanella sp. 1 at
least up to 36 degrees C, but both species show a threshold for calcification at
cold temperatures: calcification in P. calcariformata only occurred above 22
degrees C and in Lachlanella sp. 1 above 15 degrees C. Our observations from the
heat-polluted area indicate that under future warming scenarios, calcification in
heat-tolerant foraminifera species will not be inhibited during summer, but
instead the temperature window for their calcification will be expanded
throughout much of the year. The observed inhibition of calcification at low
temperatures indicates that the role of heat-tolerant foraminifera in carbonate
production will most likely increase in future decades.
PMID- 28423463
TI - Temperature regulation of marine heterotrophic prokaryotes increases
latitudinally as a breach between bottom-up and top-down controls.
AB - Planktonic heterotrophic prokaryotes make up the largest living biomass and
process most organic matter in the ocean. Determining when and where the biomass
and activity of heterotrophic prokaryotes are controlled by resource availability
(bottom-up), predation and viral lysis (top-down) or temperature will help in
future carbon cycling predictions. We conducted an extensive survey across
subtropical and tropical waters of the Atlantic, Indian and Pacific Oceans during
the Malaspina 2010 Global Circumnavigation Expedition and assessed indices for
these three types of controls at 109 stations (mostly from the surface to 4,000 m
depth). Temperature control was approached by the apparent activation energy in
eV (ranging from 0.46 to 3.41), bottom-up control by the slope of the log-log
relationship between biomass and production rate (ranging from -0.12 to 1.09) and
top-down control by an index that considers the relative abundances of
heterotrophic nanoflagellates and viruses (ranging from 0.82 to 4.83). We
conclude that temperature becomes dominant (i.e. activation energy >1.5 eV)
within a narrow window of intermediate values of bottom-up (0.3-0.6) and top-down
0.8-1.2) controls. A pervasive latitudinal pattern of decreasing temperature
regulation towards the Equator, regardless of the oceanic basin, suggests that
the impact of global warming on marine microbes and their biogeochemical function
will be more intense at higher latitudes. Our analysis predicts that 1 degrees C
ocean warming will result in increased biomass of heterotrophic prokaryoplankton
only in waters with <26 degrees C of mean annual surface temperature.
PMID- 28423465
TI - Febrile status epilepticus due to respiratory syncytial virus infection.
AB - BACKGROUND: Febrile status epilepticus can have neurological sequelae. The type
of sequelae, however, depend on the etiology, including infection due to viral
agents such as the influenza virus. Respiratory syncytial virus (RSV) infection
in childhood may also contribute to this. The aim of this study was therefore to
characterize febrile status epilepticus associated with RSV infection, and to
determine whether this type of infection is a risk factor for neurological
sequelae in febrile status epilepticus. METHODS: We reviewed the medical records
of children aged <=3 years with febrile status epilepticus who were admitted to a
tertiary hospital between January 2007 and December 2011. The differences between
the RSV-positive and RSV-negative groups were evaluated according to the
demographic and clinical data. RESULTS: A total of 99 patients with febrile
status epilepticus who had been tested for RSV infection were identified. Three
patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n
= 80) presented with bronchiolitis. The incidence of intubation and anti-seizure
drug treatment in the RSV-positive group was significantly higher than in the
negative group. While all of the patients in the RSV-negative group recovered
completely, six patients in the RSV-positive group developed encephalopathy and
profound neurological sequelae. In five of the six patients, diffusion-weighted
magnetic resonance imaging showed subcortical white matter lesions. CONCLUSIONS:
RSV infection in the absence of bronchiolitis can initially present as febrile
status epilepticus and subsequently develop into acute encephalopathy with
profound neurological sequelae.
PMID- 28423464
TI - High clinical suspicion of donor-derived disease leads to timely recognition and
early intervention to treat solid organ transplant-transmitted lymphocytic
choriomeningitis virus.
AB - Despite careful donor screening, unexpected donor-derived infections continue to
occur in organ transplant recipients (OTRs). Lymphocytic choriomeningitis virus
(LCMV) is one such transplant-transmitted infection that in previous reports has
resulted in a high mortality among the affected OTRs. We report a LCMV case
cluster that occurred 3 weeks post-transplant in three OTRs who received
allografts from a common organ donor in March 2013. Following confirmation of
LCMV infection at Centers for Disease Control and Prevention, immunosuppression
was promptly reduced and ribavirin and/or intravenous immunoglobulin therapy were
initiated in OTRs. The liver recipient died, but right kidney recipients survived
without significant sequelae and left kidney recipient survived acute LCMV
infection with residual mental status deficit. Our series highlights how early
recognition led to prompt therapeutic intervention, which may have contributed to
more favorable outcome in the kidney transplant recipients.
PMID- 28423466
TI - Zonulin transgenic mice show altered gut permeability and increased
morbidity/mortality in the DSS colitis model.
AB - Increased small intestinal permeability (IP) has been proposed to be an integral
element, along with genetic makeup and environmental triggers, in the pathogenies
of chronic inflammatory diseases (CIDs). We identified zonulin as a master
regular of intercellular tight junctions linked to the development of several
CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of
CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate
(DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to
C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight,
histology, and survival were monitored. To mechanistically link zonulin-dependent
impairment of small intestinal barrier function with clinical outcome, Ztm were
treated with the zonulin inhibitor AT1001 added to drinking water in addition to
DSS. We observed increased morbidity (more pronounced weight loss and colitis)
and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in
Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an
increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS
treatment and was associated with upregulation of zonulin gene expression
(fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001
prevented the DSS-induced increased IP both in vivo and ex vivo without changing
zonulin gene expression and completely reverted morbidity and mortality in Ztm.
Our data show that zonulin-dependent small intestinal barrier impairment is an
early step leading to the break of tolerance with subsequent development of CIDs.
PMID- 28423467
TI - Early life antibiotic use and the risk of asthma and asthma exacerbations in
children.
AB - BACKGROUND: The use of antibiotic therapy early in life might influence the risk
of developing asthma. Studies assessing the influence of early life antibiotic
use on the risk of asthma exacerbations are limited, and the results are
inconsistent. Therefore, the aim of this study was to assess the association
between use of antibiotic during the first 3 years of life and the risk of
developing childhood asthma and the occurrence of asthma exacerbations. METHODS:
Data from four large childhood cohorts were used; two population-based cohorts to
study the risk of developing asthma: Generation R (n=7393, The Netherlands) and
SEATON (n=891, Scotland, UK), and two asthma cohorts to assess the risk of asthma
exacerbations: PACMAN (n=668, The Netherlands) and BREATHE (n=806, Scotland, UK).
Odds ratios (ORs) were derived from logistic regression analysis within each
database followed by pooling the results using a fixed- or random-effect model.
RESULTS: Antibiotic use in early life was associated with an increased risk of
asthma in a meta-analysis of the Generation R and SEATON data (OR: 2.18, 95% CI:
1.04-4.60; I2 : 76.3%). There was no association between antibiotic use in early
life and risk of asthma exacerbations later in life in a meta-analysis of the
PACMAN and BREATHE data (OR: 0.93, 95% CI: 0.65-1.32; I2 : 0.0%). CONCLUSION:
Children treated with antibiotic in the first 3 years of life are more likely to
develop asthma, but there is no evidence that the exposure to antibiotic is
associated with increased risk of asthma exacerbations.
PMID- 28423468
TI - Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.
AB - Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other
organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found
in plant foods, have shown protective effects against Cd-induced damage. The
cytoprotective effects of flavonoids against Cd-induced diseases are mainly
attributable to three mechanisms. First, flavonoids clear reactive oxygen
species, thereby reducing lipid peroxide production and improving the activity of
antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the
accumulation of Cd and altering the levels of other essential metal ions in vivo.
Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition,
flavonoids were found to inhibit inflammation and fibrosis and improve
glycometabolism and the secretion of reproductive hormones. We introduce the
daily dosage and absorption rate of flavonoids and then focus on their bioactive
effects against Cd-induced toxicity and reveal the underlying metabolic pathway,
which provides a basis for further study of the nutritional prevention of Cd
induced injury. In particular, a better understanding is needed of the structure
activity relationship of flavonoids against Cd toxicity, which has not yet been
reported.
PMID- 28423469
TI - Cytomegalovirus peritonitis after kidney transplantation diagnosed through
histopathological examination.
AB - Among organ transplant recipients, cytomegalovirus (CMV) commonly results in
various types of infection such as pneumonitis, hepatitis, and enterocolitis.
However, CMV peritonitis is very rare and difficult to diagnose owing to lack of
visible clinical signs. We present a case of a 35-year-old female kidney
recipient who developed abdominal pain and urinary retention caused by CMV
peritonitis. To our knowledge, this is the first case report of CMV peritonitis
after organ transplantation to be diagnosed through histopathological
examination.
PMID- 28423470
TI - Quantification of near-attomole gibberellins in floral organs dissected from a
single Arabidopsis thaliana flower.
AB - There remains a methodological bottleneck in the quantification of ultra-trace
plant hormones in very tiny plant organs at fresh weights below a milligram. The
challenge becomes even more serious in the determination of endogenous
gibberellins (GAs), which are a class of compounds that are difficult to separate
and detect. Herein, a quantification method using ultra-high-performance liquid
chromatography-tandem mass spectrometry was developed, combined with a
derivatization technique in which GAs react with N-(3-dimethylaminopropyl)-N'
ethylcarbodiimide in ethanol. The method was validated as capable of determining
GAs in floral organs (about 80-250 MUg) - pistil, stamens, petals, sepals and
receptacle - which were dissected from only one flower of Arabidopsis thaliana.
Substantially different abundance patterns of GAs were measured from the floral
organs at floral stages 13, 14 and 15 along the non-13-hydroxylation pathway and
the early 13-hydroxylation pathway in plants. This allows sub-flower-level
insights into how GAs affect floral development. The method exhibited excellent
limit of detection and limit of quantification down to 5.41 and 18.0 attomole,
respectively, and offered a fairly wide linear range from 0.01 to 25 femtomole
with linear coefficients above 0.9961. The precision of the method was evaluated
with relative standard deviations below 10.6% for intra-day and 11.4% for inter
day assays, and recoveries ranged from 64.0% to 107%.
PMID- 28423471
TI - Career Cartography: From Stories to Science and Scholarship.
AB - PURPOSE: To present four case scenarios reflecting the process of research career
development using career cartography. ORGANIZING CONSTRUCTS: Career cartography
is a novel approach that enables nurses, from all clinical and academic settings,
to actively engage in a process that maximizes their clinical, teaching,
research, and policy contributions that can improve patient outcomes and the
health of the public. METHODS: Four early-career nurse researchers applied the
career cartography framework to describe their iterative process of research
career development. They report the development process of each of the components
of career cartography, including destination statement, career map, and policy
statement. CONCLUSIONS: Despite diverse research interests and career mapping
approaches, common experiences emerged from the four nurse researchers. Common
lessons learned throughout the career cartography process include: (a) have a
supportive mentorship team, (b) start early and reflect regularly, (c) be brief
and to the point, (d) keep it simple and avoid jargon, (e) be open to change, (f)
make time, and (g) focus on the overall career destination. CLINICAL RELEVANCE:
These four case scenarios support the need for nurse researchers to develop their
individual career cartography. Regardless of their background, career cartography
can help nurse researchers articulate their meaningful contributions to science,
policy, and health of the public.
PMID- 28423472
TI - Simultaneous structural identification of diacylglyceryl-N-trimethylhomoserine
(DGTS) and diacylglycerylhydroxymethyl-N,N,N-trimethyl-beta-alanine (DGTA) in
microalgae using dual Li+ /H+ adduct ion mode by ultra-performance liquid
chromatography/quadrupole time-of-flight mass spectrometry.
PMID- 28423473
TI - Prediction of cashew nut allergy in sensitized children.
PMID- 28423474
TI - Nasal obstructive disorders impair health-related quality of life in adolescents
with persistent allergic rhinitis: A real-life study.
AB - BACKGROUND: We previously reported a higher prevalence of nasal obstructive
disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not
responding to medical treatment. The aim of this study was to determine the
impact of NOD on quality of life (QoL) in this population. METHODS: Real-life
prospective study including 142 patients (41 children, 6-11 years old and 101
adolescents, 12-17 years old) with moderate and severe PER. After 2 months of
medical treatment (intranasal steroids and antihistamines), patients were asked
whether their symptoms had improved (yes/no) and classified accordingly in R,
responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD
(nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty
nine adolescents and 24 children were included in the NR group. NR presented
worse QoL overall scores in adolescents (3.16+/-1.1 vs 1.63+/-0.99; P=.00001) and
children (2.19+/-0.82 vs 1.51+/-0.77, P=.02). Medical treatment failure was
associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR:
1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs
2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005),
obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both
(OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and
highly significant correlation was found between nasal symptoms VAS and QoL.
CONCLUSION: The presence of NOD, particularly in adolescents, is associated with
poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an
essential approach to determine the response to treatment and its impact on
patient's QoL.
PMID- 28423475
TI - Primary lymphocytic hypophysitis: Clinical characteristics and treatment of 50
cases in a single centre in China over 18 years.
AB - OBJECTIVE: Primary lymphocytic hypophysitis (LYH) is rare, and it is often
evaluated in a small case series. This study aimed to describe the diagnosis and
treatment of primary LYH in a larger cohort. DESIGN: A retrospective study of the
diagnosis and treatment of primary LYH was conducted at Peking Union Medical
College Hospital from 1999 to 2016. PATIENTS: Fifty patients (28 histologically
diagnosed and 22 clinically-diagnosed) were eligible for inclusion. MEASUREMENTS:
Clinical, endocrine, pathological and imaging findings; therapies and outcomes
were assessed. Ordinal logistic regression analysis was used to evaluate the
association between the clinical parameters and outcomes (eg, improvements in
pituitary function, regression of lesion size on MRI and disease recurrence).
RESULTS: Central diabetes insipidus (CDI) (72.0%) was the most common endocrine
dysfunction. Hypogonadotropic hypogonadism was the most frequently observed
(60.0%) manifestation of anterior pituitary dysfunction; adrenal insufficiency
was the third most common (26.0%) manifestation; and IGF-1 axis defects were the
least frequent (22.0%). Thickening of the pituitary stalk was the most frequent
(96.0%) imaging finding, and 78.0% of the patients exhibited both intrasellar and
suprasellar expansion. Pharmacological dose of glucocorticoids was identified to
be significantly associated with increased odds of anterior pituitary function
improvement. No observed covariates were significantly associated with
improvement of CDI and recurrence. CONCLUSION: The sequence of anterior pituitary
deficiencies in Chinese primary LYH patients was atypical (LH/FSH>TSH>ACTH>IGF-1
axis deficiency). A pharmacological dose of glucocorticoids was significantly
associated with the improved anterior pituitary insufficiency.
PMID- 28423476
TI - Dietary Patterns and Alcohol Consumption During Pregnancy: Secondary Analysis of
Avon Longitudinal Study of Parents and Children.
AB - BACKGROUND: Large general population surveys show that heavy regular and episodic
alcohol consumption are associated with lower intakes of fruits and vegetables,
and higher intakes of processed and fried meat. This is of particular concern
regarding pregnant women, as both alcohol intake and inadequate maternal
nutrition are independently associated with adverse fetal outcomes. The current
study aimed to determine associations between maternal dietary patterns and
alcohol consumption during pregnancy. METHODS: Women were participating in the
Avon Longitudinal Study of Parents and Children, and provided details of alcohol
consumption at 18 weeks' gestation and diet at 32 weeks' gestation (n = 9,839).
Dietary patterns were derived from the food frequency questionnaire data using
principal components analysis. Associations between alcohol consumption and
dietary patterns were determined using multiple linear regression, adjusted for
various sociodemographic and lifestyle factors. RESULTS: After adjustment,
drinking >=1 unit/d during the first trimester (beta = 0.23 [95% CI: 0.08, 0.38];
p = 0.002) and binge drinking (>=4 units in 1 day) during the first half of
pregnancy (beta = 0.14 [95% CI: 0.07, 0.21]; p < 0.0001) were associated with
greater adherence to the "Processed" dietary pattern (high intakes of processed
meat and low intakes of fruit and vegetables). Light-to-moderate alcohol
consumption (<=1 drink/d) during the first trimester was associated with greater
adherence to the "Health conscious" dietary pattern (high intakes of fruit,
vegetables, whole grains, and fish) (beta = 0.09 [95% CI: 0.04, 0.14]; p <
0.0001). CONCLUSIONS: Two important components of health behavior during
pregnancy appear to be related: greater consumption of processed foods associated
with heavier alcohol consumption, and healthier dietary choices associated with
light-to-moderate alcohol intake. Potential synergistic effects of these
behaviors may have implications for maternal and fetal health and warrant further
investigation. A more holistic approach to addressing health behaviors in women
of reproductive age is required.
PMID- 28423477
TI - Something has shifted: Nursing students' global perspective following
international clinical placements.
AB - AIMS: To examine understandings of global health issues among nursing students
following participation in an international clinical placement during their pre
registration university education. BACKGROUND: Universities use international
clinical placements, especially in developing countries, to develop cultural
awareness in students; however, little is known about the longer term influences
on students' understandings of global nursing. DESIGN: A retrospective cross
sectional design was used, using an exploratory, descriptive qualitative
approach. METHODS: Individual semi-structured interviews were conducted in 2014
with a purposive sample of 25 pre-registration nursing students from four Western
Australian universities who undertook clinical placements across five countries.
Data were analysed using inductive thematic analysis. RESULTS: Findings highlight
that students developed new understandings around health systems including
fragility of resource access, differences in clinical practice and variances in
nursing roles between settings. Students also experienced challenges but were
able to appreciate alternative world viewpoints. CONCLUSION: International
clinical placements can develop greater awareness and help students form
realistic strategies for using their nursing skills globally. Pre-placement
training in cultural awareness and health system realities, along with strong
supervisory support, is critical to success.
PMID- 28423478
TI - A qualitative study of community nurses' decision-making around the anticipatory
prescribing of end-of-life medications.
AB - AIMS: The aim of this study was to explore community nurses' decision-making
processes around the prescribing of anticipatory medications for people who are
dying. BACKGROUND: Community nurses frequently initiate the prescribing of
anticipatory medications to help control symptoms in those who are dying.
However, little is known about their decision-making processes in relation to
when they instigate anticipatory prescribing and their discussions with families
and General Practitioners. DESIGN: A qualitative interpretive descriptive
enquiry. METHODS: A purposive sample of 11 Community Palliative Nurses and
District Nurses working in one geographical area participated. Data were
collected between March and June 2016 via audio recorded semi-structured
interviews and analysed inductively using Braun and Clarke's thematic analysis.
RESULTS: Three themes were identified: (1) Drugs as a safety net. Anticipatory
medications give nurses a sense of control in last days of life symptom
management; (2) Reading the situation. The nurse judges when to introduce
conversations around anticipatory medications, balancing the need for discussion
with the dying person and their family's likely response; (3) Playing the game.
The nurse owns the decision to initiate anticipatory medication prescribing and
carefully negotiates with the General Practitioner. CONCLUSION: Nurses view pain
control through prescribed medication as key to symptom management for dying
people. Consequently, they own the role of ascertaining when to initiate
discussions with families about anticipatory medicines. Nurses believe they
advocate for dying person and their families' needs and lead negotiations with
General Practitioners for medications to go into the home. This nurse led care
alters the traditional boundaries of the General Practitioners-nurse professional
relationship.
PMID- 28423479
TI - Does a Crossover Age Effect Exist for African American and Hispanic Binge
Drinkers? Findings from the 2010 to 2013 National Study on Drug Use and Health.
AB - BACKGROUND: Among general population studies, lower rates of binge drinking tend
to be found among African Americans and Hispanics compared to Whites. However,
among older adult populations, minority groups have been shown to be at higher
risk for binge drinking, suggesting the presence of a crossover effect from low
to high risk as a function of age. To date, limited research has examined the
crossover effect among African American and Hispanic populations compared to non
Hispanic Whites across large developmental time frames or explored variation in
risk based on income or gender. This study aimed to fill these gaps in the
literature. METHODS: Data were compiled from the 2010 to 2013 National Survey on
Drug Use and Health surveys, which provide annual, nationally representative data
on substance use behaviors among individuals aged 12 and older. Hispanic, non
Hispanic African American, and non-Hispanic White respondents were included (N =
205,198) in the analyses. RESULTS: A crossover effect was found for African
American males and females among the lowest income level (i.e., incomes less than
$20,000). Specifically, after controlling for education and marital status,
compared to Whites, risk for binge drinking was lower for African American males
at ages 18 to 24 and for females at ages 18 to 34, but higher for both African
American males and females at ages 50 to 64. No crossover effect was found for
Hispanic respondents. CONCLUSIONS: Although African Americans are generally at
lower risk for binge drinking, risk appears to increase disproportionately with
age among those who are impoverished. Explanatory factors, such as social
determinants of health prevalent within low-income African American communities
(e.g., lower education, violence exposure, housing insecurity) and potential
areas for intervention programming are discussed.
PMID- 28423480
TI - The effect of high-dose vitamin D supplementation on muscular function and
quality of life in postmenopausal women-A randomized controlled trial.
AB - OBJECTIVE: Observational studies have suggested positive associations between
serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and
quality of life. Our aim was to examine whether high-dose vitamin D
supplementation would improve these measures as compared to standard-dose vitamin
D, as well as the possible muscular effects of single nucleotide polymorphisms
(SNPs) in genes encoding vitamin D-related enzymes. DESIGN: A 12-month
randomized, double-blind, controlled trial where the participants received daily
elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the
participants were randomized to receive either capsules with vitamin D3 (20 000
IU) or matching placebos to be taken twice a week. PATIENTS: A total of 297
postmenopausal women with osteopenia or osteoporosis. MEASUREMENTS: Muscle
strength (handgrip and knee extensor strength), balance (tandem test) and quality
of life (EQ-5D) were measured at baseline and after 12 months. The subjects were
genotyped for SNPs related to vitamin D metabolism. RESULTS: Of the 297 included
women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased
in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate
increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L;
P<.01). There was no significant difference between the groups in change in
muscular strength, balance or quality of life over the intervention period.
Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene)
were associated with muscle strength and treatment effects. CONCLUSION: One-year
treatment with high-dose vitamin D had no effect on muscular strength, balance or
quality of life in postmenopausal women with osteopenia or osteoporosis as
compared to standard dose. The association between rs3829251 and muscle strength
needs confirmation in other populations.
PMID- 28423481
TI - Prevalence of Gastric Motility Disorders in Patients with Functional Dyspepsia.
AB - Background/Aims: Gastric motility abnormalities have been considered to be
pathophysiological features of functional dyspepsia (FD) that are closely related
to dyspepsia symptoms, especially postprandial distress syndrome (PDS). The aims
of this study are to (1) investigate the prevalence of gastric motility disorders
and (2) evaluate the association between gastric motility abnormalities and
dyspeptic symptoms using gastric scintigraphy in the PDS type of FD. Methods:
Forty healthy subjects and 94 PDS type FD patients were enrolled in the study.
The volunteers and patients ingested a radiolabeled (technetium-99m) solid test
meal, and scintigraphic images were recorded. Gastric accommodation and emptying
were assessed by scintigraphic imaging. The patients' dyspeptic symptoms were
also explored using self-completed symptom questionnaires with 10 variables (4
scales, 0-3 points) at the same time. Results: In 94 Japanese FD patients, the
prevalence of impaired gastric accommodation and delayed emptying were 14.9%
(14/94) and 10.6% (10/94), respectively. Gastric motility abnormalities were seen
in 25.5% (24/94) of FD patients. There was no association between gastric
motility abnormalities and dyspeptic symptoms. Conclusions: Gastric motility
abnormalities were seen in 25.5% of Japanese PDS type FD patients. However, there
was no association between gastric motility abnormalities and dyspeptic symptoms
on gastric scintigraphy.
PMID- 28423482
TI - Clerosterol from vinegar-baked radix bupleuri modifies drug transport.
AB - Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when
combined with traditional chemotherapy and data show that this combination may
modify drug transport. We isolated clerosterol from VBRB and studied its effect
on drug transporters in normal or transporter-overexpressing cells. Transporter
activity was assayed using cellular substrate concentration and transporter
expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake
in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also
decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and
Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects
on Mrp1 protein and gene expression. Further study showed clerosterol increased
OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA.
Clerosterol could suppress Pgp overexpression but not by regulating protein and
gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity
in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active
constituent of VBRB and may work against cancer multidrug resistance by
inhibiting Pgp activity.
PMID- 28423483
TI - MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription
factors (EMT-TFs) and inhibits breast cancer cell migration and invasion.
AB - MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and
progression of cancer metastasis. Here, we analyzed the expression, targets and
functional effects of miR-34a on epithelial to mesenchymal transition-inducing
transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT
inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its
correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is
downregulated in human metastatic breast cancers (MBC) compared to normal breast
tissues and is negatively correlated with clinicopathological features of MBC
patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly
inhibits cell migration and invasion, but exhibits no clear effect on BC cell
growth. We found that miR-34a is able to inactivate EMT signaling pathway with
mediatory of NOTCH1, TWIST1, and ZEB1 upon 3'-UTR activity in MBC cell lines, but
has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the
synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression
of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is
able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in
BT-549 cell line, indicating that they might be a promising therapeutic
combination against breast cancer metastasis. Epigenetic inactivation of the EMT
TFs/miR-34a pathway can potentially alter the equilibrium of these regulations,
facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR
34a alone could serve as a potential therapeutic agent for MBC, and together with
TQ, their therapeutic potential is synergistically enhanced.
PMID- 28423484
TI - miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis
hematopoietic stem/progenitor cells by targeting SOCS6.
AB - Primary myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative
neoplasm characterized by hematopoietic stem cell-derived clonal
myeloproliferation, involving especially the megakaryocyte lineage. To better
characterize how the altered expression of microRNAs might contribute to PMF
pathogenesis, we have previously performed the integrative analysis of gene and
microRNA expression profiles of PMF hematopoietic stem/progenitor cells (HSPCs),
which allowed us to identify miR-494-3p as the upregulated microRNA predicted to
target the highest number of downregulated mRNAs.To elucidate the role of miR-494
3p in hematopoietic differentiation, in the present study we demonstrated that
miR-494-3p enforced expression in normal HSPCs promotes megakaryocytopoiesis.
Gene expression profiling upon miR-494-3p overexpression allowed the
identification of genes commonly downregulated both after microRNA overexpression
and in PMF CD34+ cells. Among them, suppressor of cytokine signaling 6 (SOCS6)
was confirmed to be a miR-494-3p target by luciferase assay. Western blot
analysis showed reduced level of SOCS6 protein as well as STAT3 activation in miR
494-3p overexpressing cells. Furthermore, transient inhibition of SOCS6
expression in HSPCs demonstrated that SOCS6 silencing stimulates
megakaryocytopoiesis, mimicking the phenotypic effects observed upon miR-494-3p
overexpression. Finally, to disclose the contribution of miR-494-3p upregulation
to PMF pathogenesis, we performed inhibition experiments in PMF HSPCs, which
showed that miR-494-3p silencing led to SOCS6 upregulation and impaired
megakaryocyte differentiation.Taken together, our results describe for the first
time the role of miR-494-3p during normal HSPC differentiation and suggest that
its increased expression, and the subsequent downregulation of its target SOCS6,
might contribute to the megakaryocyte hyperplasia commonly observed in PMF
patients.
PMID- 28423485
TI - M2 polarization of macrophages facilitates arsenic-induced cell transformation of
lung epithelial cells.
AB - The alterations in microenvironment upon chronic arsenic exposure may contribute
to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play
an important role in mediating the microenvironment in the lungs. Macrophages
carry out their functions after activation. There are two activation status for
macrophages: classical (M1) or alternative (M2); the latter is associated with
tumorigenesis. Our previous work showed that long-term arsenic exposure induces
transformation of lung epithelial cells. However, the crosstalk between
epithelial cells and macrophages upon arsenic exposure has not been investigated.
In this study, using a co-culture system in which human lung epithelial cells are
cultured with macrophages, we determined that long-term arsenic exposure
polarizes macrophages towards M2 status through ROS generation. Co-culture with
epithelial cells further enhanced the polarization of macrophages as well as
transformation of epithelial cells, while blocking macrophage M2 polarization
decreased the transformation. In addition, macrophage M2 polarization decreased
autophagy activity, which may account for increased cell transformation of
epithelial cells with co-culture of macrophages.
PMID- 28423486
TI - Tick-host conflict: immunoglobulin E antibodies to tick proteins in patients with
anaphylaxis to tick bite.
AB - Tick-borne infectious diseases and allergies are a growing problem worldwide.
Tick bite allergy has been associated with the direct effect of immunoglobulin E
(IgE) response to tick salivary antigens, or secondary to the induction of
allergy to red meat consumption through IgE antibodies against the carbohydrate
alpha-Gal (Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R). However, despite the growing
burden of this pathology, the proteins associated with anaphylaxis to tick bite
have not been characterized. To address this question, a comparative proteomics
approach was used to characterize tick proteins producing an IgE antibody
response in a healthy individual with record of tick bites, which had not
resulted in any allergic reactions, and two patients with anaphylactic reactions
to Rhipicephalus bursa or Hyalomma marginatum tick bites. Both patients and the
healthy individual were red meat tolerant. The results supported a patient
specific IgE antibody response to tick species responsible for the anaphylaxis to
tick bite. Both patients and the healthy individual serologically recognized tick
proteins with and without alpha-Gal modifications, with proteins differentially
recognized by patients but not control sera. These proteins could be used as
potential antigens for diagnostics, treatment and prevention of tick bite-induced
allergies.
PMID- 28423487
TI - Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory
T cells in long-term survivors with advanced melanoma.
AB - Ipilimumab has revolutionized malignant melanoma therapy, but a better
understanding of the mechanisms behind treatment response and adverse effects is
needed. In this work, the immune system of ipilimumab treated patients was
monitored to investigate potential mechanisms of action that may correlate with
treatment outcome. Blood samples from 43 advanced melanoma patients were taken
before, during and at the end of treatment. Hematological parameters were
measured and flow cytometry analysis was performed in fresh samples within two
hours of sample collection. Strong differences in markers CD45RA, CCR7, HLA-DR
and CD15 between fresh and cryopreserved samples were observed. Ipilimumab
treatment increased absolute lymphocyte counts, eosinophils, effector T cells and
their activation status, whilst diminishing the suppressive side of the immune
response, acting on regulatory T cells and myeloid derived suppressor cells
(MDSCs). These effects were visible after one ipilimumab infusion and, regarding
eosinophil counts, correlated with onset of adverse events. Monocytic MDSCs were
decreased in response to treatment only in patients with clinical benefit;
additionally, patients with a lower frequency of these cells after the first
ipilimumab infusion experienced increased overall survival. CD8 effector memory T
cell frequencies at the end of treatment were higher in patients with clinical
benefit and positively correlated with survival. These data show that a clinical
response to ipilimumab not only requires reshaping T cell populations, but
additionally involves a reduction in suppressive cells such as monocytic MDSCs.
Our work could provide insight on predicting treatment outcome, assisting
clinicians in offering the best personalized therapeutic approach.
PMID- 28423488
TI - MMP8 polymorphism is associated with susceptibility to osteonecrosis of the
femoral head in a Chinese Han population.
AB - Osteonecrosis of the femoral head (ONFH) is an orthopedic refractory disease that
adversely affects quality of life. Matrix metalloproteinase-8 (MMP-8) produced by
the bone marrow has been implicated in the degradation of collagen during bone
development. We assessed whether MMP8 polymorphisms are associated with ONFH. In
a case-control study, using chi2 tests and genetic model analyses, we genotyped 5
MMP8 single-nucleotide polymorphisms (SNPs) in 585 ONFH patients and 507 healthy
control subjects in a Chinese Han population. The MMP8 rs11225394 SNP was
associated with an increased risk of ONFH in an allele model (OR=1.34; 95% CI,
1.003-1.786, P=0.047). In addition, rs11225394 was associated with an increased
risk of ONFH in a dominant model (OR =1.39, 95% CI, 1.02-1.89, P=0.036), over
dominant model (OR=1.39, 95% CI, 1.02-1.89, P=0.038), and log-additive model (OR
=1.36, 95% CI, 1.01-1.84, P=0.039). After adjusting for age and gender,
rs11225394 was associated with ONFH in a dominant (OR =1.44, 95% CI, 1.05-1.96,
P=0.023), over-dominant (OR =1.44, 95% CI, 1.05-1.98, P=0.022), and log-additive
model (OR =1.40, 95% CI, 1.04-1.90, P=0.027). These results provide the first
evidence that MMP8 SNP at the rs11225394 locus is associated with the increased
risk of ONFH in Chinese Han population.
PMID- 28423489
TI - Target of obstructive sleep apnea syndrome merge lung cancer: based on big data
platform.
AB - Based on our hospital database, the incidence of lung cancer diagnoses was
similar in obstructive sleep apnea Syndrome (OSAS) and hospital general
population; among individual with a diagnosis of lung cancer, the presence of
OSAS was associated with an increased risk for mortality. In the gene expression
and network-level information, we revealed significant alterations of molecules
related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer
cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway
important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly
available datasets to validate that the late-stage lung adenocarcinoma patients
showed higher expression HK2 and GBE1 than early-stage ones. In terms of
prognostic features, a survival analysis revealed that the high GBE1 and HK2
expression group exhibited poorer survival in lung adenocarcinoma patients. By
analyzing and integrating multiple datasets, we identify molecular convergence
between hypoxia and lung cancer that reflects their clinical profiles and reveals
molecular pathways involved in hypoxic-induced lung cancer progression. In
conclusion, we show that OSAS severity appears to increase the risk of lung
cancer mortality.
PMID- 28423490
TI - Reappraisal of XRCC1 Arg194Trp polymorphism and glioma risk: a cumulative meta
analysis.
AB - The association between XRCC1 Arg194Trp polymorphism and glioma risk were
inconsistent from published meta-analyses and epidemiological studies. Hence, we
performed this updated and cumulative meta-analysis to reappraisal this
relationship. PubMed, Embase, CBM (Chinese Biomedical Database), and CNKI (China
National Knowledge Internet) databases were comprehensively searched up to August
13, 2016 (updated on December 22, 2016). After study selection and data
extraction from eligible studies, the association was evaluated by odds ratios
(ORs) and its 95% confidence intervals (95%CIs) using Comprehensive Meta-Analysis
software. Finally 16 case-control studies involving 7011 patients and 9519
healthy controls were yielded. The results indicated that XRCC1 Arg194Trp
polymorphism was significantly correlated with the increased risk of glioma [Trp
vs. Arg: OR = 1.18(1.05-1.34); TrpTrp vs. ArgArg: OR = 1.66(1.31-2.12); ArgTrp
vs. ArgArg: OR = 1.34(1.02-1.77); TrpTrp vs. ArgArg+ArgTrp: OR = 1.47(1.26-1.72);
TrpTrp+ArgTrp vs. ArgArg: OR = 1.17(1.01-1.35)]. Cumulative analysis showed the
results changed from non-significant to significant when new studies accumulated,
and sensitivity analysis indicated the results were stable. Subgroup analysis
showed the significant association existed in Asians but not in Caucasians.
Current evidence indicated that XRCC1 Arg194Trp polymorphism was associated with
increased risk for glioma, especially in Asians; however, relevant studies
involving other ethnic groups are required to validate our findings in further.
PMID- 28423491
TI - The miR-25-93-106b cluster regulates tumor metastasis and immune evasion via
modulation of CXCL12 and PD-L1.
AB - The stromal microenvironment controls response to injury and inflammation, and is
also an important determinant of cancer cell behavior. However, our understanding
of its modulation by miRNA (miR) and their respective targets is still sparse.
Here, we identified the miR-25-93-106b cluster and two new target genes as
critical drivers for metastasis and immune evasion of cancer cells. Using miR-25
93-106b knockout mice or antagomiRs, we demonstrated regulation of the production
of the chemoattractant CXCL12 controlling bone marrow metastasis. Moreover, we
identified the immune checkpoint PD-L1 (CD274) as a novel miR-93/106b target
playing a central role in diminishing tumor immunity. Eventually, upregulation of
miR-93 and miR-106b via miR-mimics or treatment with an epigenetic reader domain
(BET) inhibitor resulted in diminished expression of CXCL12 and PD-L1. These data
suggest a potential new therapeutic rationale for use of BET inhibitors for dual
targeting of cancers with strong immunosuppressive and metastatic phenotypes.
PMID- 28423492
TI - ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer
cells.
AB - ONC201 was previously identified as a first-in-class antitumor agent and small
molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing
ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile
and is currently in phase II clinical trials for the treatment of various
malignancies. In the current study, we examine the effect of ONC201 on triple
negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive
to TRAIL. We find that ONC201 inhibits the growth of TNBC cells including TNBC
cells that have developed acquired TRAIL resistance. However, TNBC cells that
have developed acquired ONC201 resistance are cross-resistant to TRAIL.
Mechanistically, ONC201 triggers an integrated stress response (ISR) involving
the activation of the transcription factor ATF4. Knockdown of ATF4 impairs ONC201
induced apoptosis of TNBC cells. Importantly, the activation of ATF4 is
compromised in ONC201-resistant TNBC cells. Thus, our results indicate that
ONC201 induces an ISR to cause TNBC cell death and suggest that TNBC patients may
benefit from ONC201-based therapies.
PMID- 28423493
TI - Clinical significance of detecting circulating tumor cells in colorectal cancer
using subtraction enrichment and immunostaining-fluorescence in situ
hybridization (SE-iFISH).
AB - Circulating tumor cells (CTC) are useful in early detection of colorectal cancer.
This study described a newly developed platform, integrated subtraction
enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), to
assess CTCs in colorectal cancer. CTCs were detected by SE-iFISH in 40 of 44
preoperative colorectal cancer patients, and yielded a sensitivity of 90.9%,
which was significantly higher than CellSearch system (90.9% vs. 43.2%, P=0.033).
No significant association was found between tumor stage, survival and
preoperative CTC number. CTCs were detected in 10 colorectal cancer patients one
week after surgery; seven patients with decreased CTC numbers (compared with
preoperative CTC number) were free of recurrence; whereas two of the three
patients with increased CTC numbers had tumor recurrence. Moreover, CTCs were
detected in 34 colorectal cancer patients three months after surgery; patients
with CTC<2 at three months after surgery had significantly longer Progression
Free Survival than those with CTC>=2 (P=0.019); patients with decreased CTC
number (compared with preoperative CTC number) had significantly longer
Progression Free Survival than those with increased CTC number (P=0.003). In
conclusion, CTCs could be detected in various stages of colorectal cancer using
SE-iFISH. Dynamic monitoring of CTC numbers could predict recurrence and
prognosis.
PMID- 28423494
TI - Control of long-distance cell-to-cell communication and autophagosome transfer in
squamous cell carcinoma via tunneling nanotubes.
AB - Tunneling nanotubes (TnTs) are thin channels that temporally connect nearby cells
allowing the cell-to-cell trafficking of biomolecules and organelles. The
presence or absence of TnTs in human neoplasms and the mechanisms of TnT assembly
remains largely unexplored. In this study, we have identified TnTs in tumor cells
derived from squamous cell carcinomas (SCC) cultured under bi-dimensional and tri
dimensional conditions and also in human SCC tissues. Our study demonstrates that
TnTs are not specific of epithelial or mesenchymal phenotypes and allow the
trafficking of endosomal/lysosomal vesicles, mitochondria, and autophagosomes
between both types of cells. We have identified focal adhesion kinase (FAK) as a
key molecule required for TnT assembly via a mechanism involving the MMP-2
metalloprotease. We have also found that the FAK inhibitor PF-562271, which is
currently in clinical development for cancer treatment, impairs TnT formation.
Finally, FAK-deficient cells transfer lysosomes/autophagosomes to FAK-proficient
cells via TnTs which may represent a novel mechanism to adapt to the stress
elicited by impaired FAK signaling. Collectively, our results strongly suggest a
link between FAK, MMP-2, and TnT, and unveil new vulnerabilities that can be
exploited to efficiently eradicate cancer cells.
PMID- 28423495
TI - Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting
cancer stem cells.
AB - The dismal prognosis of locally advanced and metastatic squamous cell carcinoma
of the head and neck (HNSCC) is primarily due to the development of resistance to
chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor
(EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival,
cancer stem cells (CSCs), and resistance to CRT. Here we investigated the
radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro
and in vivo. Our results showed strong antiproliferative effects of afatinib in
HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial
cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects
with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in
vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to
epithelial transition, G1 cell cycle arrest, and the attenuating ionizing
radiation (IR)-induced activation of DNA double strand break repair (DSB)
ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on
tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and
decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we
observed that a combination of afatinib with IR significantly reduced SCC1
xenograft tumors (median weight of 168.25 +/- 20.85 mg; p = 0.05) compared to
afatinib (280.07 +/- 20.54 mg) or IR alone (324.91 +/- 28.08 mg).
Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation
of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated
gammaH2AX by afatinib. Overall, afatinib reduces tumorigenicity and
radiosensitizes HNSCC cells. It holds promise for future clinical development as
a novel radiosensitizer by improving CSC eradication.
PMID- 28423496
TI - mTOR inhibitors activate PERK signaling and favor viability of gastrointestinal
neuroendocrine cell lines.
AB - mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently
activated in cancer cells. The mTOR pathway has been shown to be up-regulated in
most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known
about the UPR status in neoplastic neuroendocrine cells. However, these hormone
producing cells are likely to present distinctive adaptations of this pathway, as
other secretory cells. We therefore analyzed the status of the three axes of UPR
and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors
(GI-NET) cell lines STC-1 and GluTag. At baseline, pharmacological inducers
activate the three arms of UPR: PERK, ATF6 and IRE1. Although hypoxia stimulates
the PERK, ATF6 and IRE-1 pathways in both cell lines, glucose depletion activates
UPR only in STC-1 cell line. Strikingly, P-p70S6K1 increases concomitantly to P
PERK and BiP in response to thapsigargin treatment, glucose depletion or hypoxia.
We found that different mTOR inhibitors activate the PERK signaling pathway. To
confirm that mTOR inhibition modulates PERK activation, we inhibited PERK and
showed that it decreased cell viability when associated to mTOR inhibition,
indicating that mTOR drives a PERK-dependent survival pathway. In conclusion, in
GI-NET cell lines, UPR signaling is functional and PERK arm is induced by mTOR
inhibition. These observations open up new perspectives for therapeutic
strategies: the crosstalk between mTOR and UPR might contribute to the resistance
to mTOR inhibitors and could be targeted by mTOR and PERK inhibitors in
combination therapy.
PMID- 28423497
TI - Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal
tubular epithelial cells by improving mitochondrial function.
AB - Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients.
There is increasing evidence that mitochondrial dysfunction plays an important
role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is
carried out by mitophagy. Although mitophagy is considered of particular
importance in protecting against AKI, little is known of the precise role of
mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity.
Also, evidence that activation of mitophagy improved mitochondrial function is
lacking. Furthermore, several evidences have shown that mitochondrial fission
coordinates with mitophagy. The aim of this study was to investigate whether
activation of mitophagy protects against mitochondrial dysfunction and renal
proximal tubular cells injury during cisplatin treatment. The effect of
mitochondrial fission on mitophagy was also investigated. In cultured human renal
proximal tubular cells, we observed that 3-methyladenine, a pharmacological
inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced
mitochondrial dysfunction and cells injury. In contrast, autophagy activator
rapamycin enhanced mitophagy and protected against the harmful effects of
cisplatin on mitochondrial function and cells viability. Suppression of
mitochondrial fission by knockdown of its main regulator dynamin-related protein
1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1 suppression
protected against cisplatin-induced cells injury by inhibiting mitochondrial
dysfunction. Our results provide evidence that Drp1-depedent mitophagy has
potential as renoprotective targets for the treatment of cisplatin-induced AKI.
PMID- 28423498
TI - The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid
invasiveness.
AB - Tumor metastasis profoundly reduces the survival of breast cancer patients, but
the mechanisms underlying breast cancer invasiveness and metastasis are
incompletely understood. Here, we report that the E3 ubiquitin ligase Smurf2 acts
in a sumoylation-dependent manner to suppress the invasive behavior of MDA-MB-231
human breast cancer cell-derived organoids. We also find that the SUMO E3 ligase
PIAS3 inhibits the invasive growth of breast cancer cell-derived organoids. In
mechanistic studies, PIAS3 maintains breast cancer organoids in a non-invasive
state via sumoylation of Smurf2. Importantly, the E3 ubiquitin ligase activity is
required for sumoylated Smurf2 to suppress the invasive growth of breast cancer
cell derived organoids. Collectively, our findings define a novel role for the
PIAS3-Smurf2 sumoylation pathway in the suppression of breast cancer cell
invasiveness. These findings lay the foundation for the development of novel
biomarkers and targeted therapeutic approaches in breast cancer.
PMID- 28423499
TI - Imidazoline I2 receptor inhibitor idazoxan regulates the progression of hepatic
fibrosis via Akt-Nrf2-Smad2/3 signaling pathway.
AB - Liver fibrosis is a global health problem and its relationship with imidazoline
I2 receptor has not been reported. This study aimed to investigate the effects
and underlying mechanisms of imidazoline I2 receptor (I2R) inhibitor idazoxan
(IDA) on carbon tetrachloride (CCl4)-induced liver fibrosis. In vivo liver
fibrosis in mice was induced by intraperitoneally injections of CCl4 for eight
weeks, and in vitro studies were performed on activated LX2 cells treated with
transforming growth factor-beta (TGF-beta). Our results showed that IDA
significantly improved liver inflammation, ameliorated hepatic stellate cells
activation and reduced collagen accumulation by suppressing the pro-fibrogenic
signaling of TGF-beta/Smad. Further investigation showed that IDA significantly
balanced oxidative stress through improving the expressions and activities of
anti-oxidant and detoxifying enzymes and activating Nrf2-the key defender against
oxidative stress with anti-fibrotic potentials. Even more impressively, knock out
of Nrf2 or suppression of Akt by perifosine (PE) eliminated the anti-oxidant and
anti-fibrotic effects of IDA in vivo and in vitro, suggesting that Akt/Nrf2
constitutes a critical component of IDA's protective functions. Taken together,
IDA exhibits potent effects against liver fibrosis via Akt-Nrf2-Smad2/3 signaling
pathway, which suggests that specifically targeting I2R may be a potentially
useful therapeutic strategy for liver fibrosis.
PMID- 28423500
TI - The role of hesperetin on osteogenesis of human mesenchymal stem cells and its
function in bone regeneration.
AB - Hesperetin has been suggested to be involved in bone strength. We aimed to
investigate the effects of hesperetin on the osteogenic differentiation of human
mesenchymal stem cells and its related mechanisms. We showed that hesperetin
promoted osteogenic differentiation of human mesenchymal stem cells in vitro. It
potentially exerts its effects via the ERK and Smad signaling pathways. Using a
rat osteotomy model, we showed that human mesenchymal stem cells combined with a
hesperetin/gelatin sponge scaffold resulted in accelerated fracture healing in
vivo. Due to the low cost of hesperetin, it could be used as a growth factor for
bone tissue engineering or surgical fracture treatment.
PMID- 28423501
TI - Epigenetic silencing of miR-520c leads to induced S100A4 expression and its
mediated colorectal cancer progression.
AB - The S100 calcium-binding protein A4 (S100A4) induces epithelial mesenchymal
transition, migration, invasion, angiogenesis and metastasis. Its induced
expression in several cancer types correlates with poor prognosis. Apart from the
functional and transcriptional regulatory aspects of S100A4, its post
transcriptional regulation is not yet clearly elucidated. In this study, we show
that microRNAs (miR) miR-505-5p and miR-520c-3p target the 3'-UTR of S100A4 and
inhibits its expression and its mediated migration and invasion. 5-Aza treatment
significantly increased miR-520c-3p expression and reduced the S100A4 protein
amounts. The upstream promoter region of miR-520c is hypermethylated irrespective
of the metastasis status of colorectal cancer (CRC) patient tissues and in all
analyzed CRC cell lines. Moreover, in a cohort of CRC patient specimen (n = 59),
miR-520c-3p was significantly downregulated. miR-520c-3p stably expressing HCT116
cells showed a reduced metastasis formation in livers after implanting in mice
spleen. Taken together, our findings demonstrate that S100A4 is post
transcriptionally regulated by tumor suppressor miRs, miR-505c-5p and miR-520c
3p, and particularly miR-520c-3p expression is epigenetically silenced in CRC.
PMID- 28423502
TI - Acute lymphoblastic leukemia cells are sensitive to disturbances in protein
homeostasis induced by proteasome deubiquitinase inhibition.
AB - The non-genotoxic nature of proteasome inhibition makes it an attractive
therapeutic option for the treatment of pediatric malignancies. We recently
described the small molecule VLX1570 as an inhibitor of proteasome deubiquitinase
(DUB) activity that induces proteotoxic stress and apoptosis in cancer cells.
Here we show that acute lymphoblastic leukemia (ALL) cells are highly sensitive
to treatment with VLX1570, resulting in the accumulation of polyubiquitinated
proteasome substrates and loss of cell viability. VLX1570 treatment increased the
levels of a number of proteins, including the chaperone HSP70B', the oxidative
stress marker heme oxygenase-1 (HO-1) and the cell cycle regulator p21Cip1.
Unexpectedly, polybiquitin accumulation was found to be uncoupled from ER stress
in ALL cells. Thus, increased phosphorylation of eIF2alpha occurred only at supra
pharmacological VLX1570 concentrations and did not correlate with polybiquitin
accumulation. Total cellular protein synthesis was found to decrease in the
absence of eIF2alpha phosphorylation. Furthermore, ISRIB (Integrated Stress
Response inhibitor) did not overcome the inhibition of protein synthesis. We
finally show that VLX1570 can be combined with L-asparaginase for additive or
synergistic antiproliferative effects on ALL cells. We conclude that ALL cells
are highly sensitive to the proteasome DUB inhibitor VLX1570 suggesting a novel
therapeutic option for this disease.
PMID- 28423503
TI - Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of
adriamycin in a gold nanoshell-based drug/gene co-delivery system.
AB - Rap2b is a novel p53 target we have identified recently. Knockdown of Rap2b
sensitizes HCT116 cells to adriamycin-induced apoptosis, indicating that Rap2b
promotes adriamycin resistance in cancer cells. In the present study, we designed
a nanostructure-based drug/gene delivery system to evaluate the potential of
Rap2b siRNA as a therapeutic agent against human cancers. Specifically, after co
incubated with HCT116 cells, adriamycin- and Rap2b siRNA-loaded gold nanoshells
were internalized. Subsequent laser irradiation promoted release of adriamycin
and Rap2b siRNA from the nanoparticles. The laser-induced release of Rap2b siRNA
decreased cellular expression of Rap2b and significantly enhanced the anticancer
therapeutic efficacy of adriamycin in vitro and in vivo. In addition, laser
irradiation of the nanoparticles might exert an additional thermal killing effect
on cancer cells and further improved the anticancer efficacy of adriamycin. In
summary, Rap2b siRNA is a potential enhancing agent for adriamycin-based
anticancer therapeutics and the gold nanoshell-based drug/gene delivery system
carrying both adriamycin and Rap2b siRNA provides a promising anticancer
therapeutic strategy.
PMID- 28423504
TI - Variations in the bitterness perception-related genes TAS2R38 and CA6 modify the
risk for colorectal cancer in Koreans.
AB - Bitterness perception is known to be an important factor in individuals' dietary
behaviors and is also associated with the sensing of nutritious/noxious molecules
for subsequent metabolic responses in multiple organs. Therefore, the genetic
variation in bitterness sensing may be associated with diet-related diseases,
including colorectal cancer (CRC). We investigated the influence of variations in
the bitterness-sensing genes taste receptor type 2 member 38 (TAS2R38) and
carbonic anhydrase 6 (CA6) on the consumption of food, tobacco and alcohol and
the risk of CRC in Koreans. The study population consisted of 681 cases and 1361
controls, and their intake of vegetables, fruits, fiber, fat-food and sweets was
analyzed. The genotypes for TAS2R38 A49P, V262A and I296V and CA6 rs2274333 A/G
were assessed using the MassArray technique. Our findings suggested that the
TAS2R38 diplotype, CA6 rs2274333 and their combined genotype had a negligible
influence on dietary and alcohol intake. The combined TAS2R38-CA6 AVI/AVI-AA
genotype was associated with higher tobacco consumption than the other genotypes
in CRC cases only. However, the genetic variations were a significant risk factor
for CRC. The TAS2R38 AVI/AVI diplotype and CA6 G allele were associated with a
reduced risk of CRC. Moreover, when the combined genotypes of the subjects were
analyzed, possessing both the variant diplotype/variant allele (AVI/AVI+G*) was
associated with a greater reduction in the risk of CRC (adjusted OR = 0.49;
95%CI: 0.34-0.74). In summary, variations in the bitterness perception genes
TAS2R38 and CA6 did not influence the examined food intake in Koreans. However,
those genetic variants were a decisive modifying factor of CRC susceptibility.
PMID- 28423505
TI - Identification and analysis of mutational hotspots in oncogenes and tumour
suppressors.
AB - BACKGROUND: The key to interpreting the contribution of a disease-associated
mutation in the development and progression of cancer is an understanding of the
consequences of that mutation both on the function of the affected protein and on
the pathways in which that protein is involved. Protein domains encapsulate
function and position-specific domain based analysis of mutations have been shown
to help elucidate their phenotypes. RESULTS: In this paper we examine the domain
biases in oncogenes and tumour suppressors, and find that their domain
compositions substantially differ. Using data from over 30 different cancers from
whole-exome sequencing cancer genomic projects we mapped over one million
mutations to their respective Pfam domains to identify which domains are enriched
in any of three different classes of mutation; missense, indels or truncations.
Next, we identified the mutational hotspots within domain families by mapping
small mutations to equivalent positions in multiple sequence alignments of
protein domainsWe find that gain of function mutations from oncogenes and loss of
function mutations from tumour suppressors are normally found in different domain
families and when observed in the same domain families, hotspot mutations are
located at different positions within the multiple sequence alignment of the
domain. CONCLUSIONS: By considering hotspots in tumour suppressors and oncogenes
independently, we find that there are different specific positions within domain
families that are particularly suited to accommodate either a loss or a gain of
function mutation. The position is also dependent on the class of mutation.We
find rare mutations co-located with well-known functional mutation hotspots, in
members of homologous domain superfamilies, and we detect novel mutation hotspots
in domain families previously unconnected with cancer. The results of this
analysis can be accessed through the MOKCa database
(http://strubiol.icr.ac.uk/extra/MOKCa).
PMID- 28423506
TI - Granulocyte colony-stimulating factor enhances the therapeutic efficacy of bone
marrow mesenchymal stem cell transplantation in rats with experimental acute
pancreatitis.
AB - INTRODUCTION: Acute pancreatitis (AP) is one of the most common diseases
involving necrotic inflammation. Bone marrow mesenchymal stem cells (BMMSCs) have
the potential of multi-directional differentiation and self-renewal for tissue
repair. It remains less clear if granulocyte colony-stimulating factor (G-CSF)
can improve the therapeutic effect of BMMSC transplant in AP. Therefore, we
explored this issue in a rat model of experimental AP. RESULTS: Transplanted
PKH26-positive BMMSCs were present in the injured pancreatic tissue, with some
cells co-expressed pancreatic cellular markers, including Pax-4, Ngn3 and Nkx-6.
Pathological, biochemical and serological data suggested an improvement in
histological and functional recovery in these animals relative to control.
Overall, the AP model rats received BMMSCs and G-CSF co-treatment showed better
recovery in terms of tissue regeneration and blood biochemical levels relative to
other groups. MATERIALS AND METHODS: BMMSCs from donor rats were labeled with the
fluorescent dye PKH26 and transfused into recipient rats with AP induced by L
arginine. The animals were divided into a control group, and groups treated with
BMMSCs, G-CSF, and BMMSCs together with G-CSF. Therapeutic effects were evaluated
histologically with immunohistochemistry and immunofluorescence, together with
biochemical measurement of pancreatic markers. CONCLUSION: G-CSF therapy with
BMMSC transplantation improves histological and functional outcomes in rats with
experimental AP.
PMID- 28423507
TI - TGF-beta-independent CTGF induction regulates cell adhesion mediated drug
resistance by increasing collagen I in HCC.
AB - Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic
agents and remains an unmet medical need. Here, we demonstrate a mechanism of
cell adhesion-mediated drug resistance using a variety of HCC spheroid models to
overcome environment-mediated drug resistance in HCC. We classified spheroids
into two groups, tightly compacted and loosely compacted aggregates, based on
investigation of dynamics of spheroid formation. Our results show that
compactness of HCC spheroids correlated with fibroblast-like characteristics,
collagen 1A1 (COL1A1) content, and capacity for chemoresistance. We also showed
that ablation of COL1A1 attenuated not only the capacity for compact-spheroid
formation, but also chemoresistance. Generally, connective tissue growth factor
(CTGF) acts downstream of transforming growth factor (TGF)-beta and promotes
collagen I fiber deposition in the tumor microenvironment. Importantly, we found
that TGF-beta-independent CTGF is upregulated and regulates cell adhesion
mediated drug resistance by inducing COL1A1 in tightly compacted HCC spheroids.
Furthermore, losartan, which inhibits collagen I synthesis, impaired the
compactness of spheroids via disruption of cell-cell contacts and increased the
efficacy of anticancer therapeutics in HCC cell line- and HCC patient-derived
tumor spheroids. These results strongly suggest functional roles for CTGF-induced
collagen I expression in formation of compact spheroids and in evading anticancer
therapies in HCC, and suggest that losartan, administered in combination with
conventional chemotherapy, might be an effective treatment for liver cancer.
PMID- 28423508
TI - Annexin A13 promotes tumor cell invasion in vitro and is associated with
metastasis in human colorectal cancer.
AB - PURPOSE: Aberrantly upregulated expression of selected members of annexin, a
group of calcium- and membrane-binding proteins, have been found to be associated
with metastasis, poor prognosis, and other clinical characteristics in colorectal
cancer (CRC), the third most diagnosed cancer. However, ANXA13 (encoding protein
annexin A13), the original founder gene of the annexin A family, has not been
studied carefully as a potential prognostic biomarker in CRC. METHODS: The
protein level of annexin A13 was determined by western blot in a panel of CRC
cell lines. Tumor cell invasion was determined by a Matrigel in vitro invasion
assay in selected CRC cells with either upregulated (via plasmid transfection) or
downregulated (via siRNA treatment) expression of ANXA13. The clinicopathological
features and prognostic values associated with ANXA13 expression were also
evaluated in a group of 125 CRC patients. RESULTS: ANXA13 was expressed at a high
level in HCT116 and HT29 cells but undetected or at a lower level in SW620, SW48,
and Rko cells. CRC cell invasion was promoted by ANXA13 overexpression in SW620
or Rko cells and was reduced by ANXA13 downregulation in HCT116 or HT29 cells. In
CRC patients, ANXA13 expression levels correlated with lymph node metastasis and
were associated with poor overall survival. CONCLUSIONS: ANXA13 is associated
with CRC cell invasion in vitro, and with lymph node metastasis and poor survival
in CRC patients. Our results indicate that ANXA13 can be exploited as a biomarker
for its diagnostic and prognostic values.
PMID- 28423509
TI - Histone lysine methyltransferase G9a is a novel epigenetic target for the
treatment of hepatocellular carcinoma.
AB - Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone
lysine methyltransferase G9a and is associated with the repression of
transcription. However, both the role of G9a and the significance of H3K9me2 in
hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted
loss-of-function assay of G9a using short-hairpin RNA and pharmacological
interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell
growth and sphere formation. However, transforming growth factor beta1-induced
epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown.
Combined analyses of chromatin immunoprecipitation followed by sequencing and RNA
sequencing led to successful identification of 96 candidate epigenetic targets of
G9a. Pharmacological inhibition of G9a by BIX-01294 resulted in both cell growth
inhibition and induction of apoptosis in HCC cells. Intraperitoneal
administration of BIX-01294 suppressed the growth of xenograft tumors generated
by implantation of HCC cells in non-obese diabetic/severe combined
immunodeficient mice. Immunohistochemical analyses revealed high levels of G9a
and H3K9me2 in 36 (66.7%) and 35 (64.8%) primary HCC tissues, respectively. G9a
expression levels were significantly positively correlated with H3K9me2 levels in
tumor tissues. In contrast, in non-tumor tissues, G9a and H3K9me2 were only
observed in biliary epithelial cells and periportal hepatocytes. In conclusion,
G9a inhibition impairs anchorage-dependent and -independent cell growth, but not
EMT in HCC cells. Our data indicate that pharmacological interference of G9a
might be a novel epigenetic approach for the treatment of HCC.
PMID- 28423510
TI - Genistein inhibits the growth and regulates the migration and invasion abilities
of melanoma cells via the FAK/paxillin and MAPK pathways.
AB - Genistein is one of the main components of soy-based foods, which are widely
known for their many benefits, including anti-cancer, anti-inflammatory, and
antioxidant effects. In this study, we investigated the anti-metastasis effects
of genistein on B16F10 melanoma cells. Our results showed that genistein strongly
inhibited B16F10 cell proliferation and induced apoptosis in time- and
concentration-dependent manners. Genistein altered the morphology of B16F10 cells
to an elongated shape with slim pseudopodia-like protrusions. Moreover, genistein
inhibited the invasion and migration abilities of B16F10 cells in a dose
dependent manner. On one hand, a high concentration of genistein (100 MUM)
significantly inhibited cell adhesion and migration, as shown by wound healing
assays and transwell-migration and invasion assays. Furthermore, the expression
levels of p-FAK, p-paxillin, tensin-2, vinculin, and alpha-actinin were decreased
by genistein. As a result, genistein is believed to strongly downregulate the
migration and invasion abilities of B16F10 cells via the FAK/paxillin pathway.
Moreover, p-p38, p-ERK, and p-JNK levels were also dramatically decreased by
treatment with genistein. Finally, genistein significantly decreased the gene
expression of FAK, paxillin, vimentin, and epithelial-to-mesenchymal transition
related transcription factor Snail, as shown by real-time PCR (qPCR) analysis. On
the other hand, a lower concentration of genistein (12.5 MUM) significantly
promoted both invasion and migration by activating the FAK/paxillin and MAPK
signaling cascades. Taken together, this study showed for the first time that
genistein exerts dual functional effects on melanoma cells. Our findings suggest
that genistein regulates the FAK/paxillin and MAPK signaling pathways in a highly
concentration-dependent manner. Patients with melanoma should therefore be
cautious of consuming soy-based foods in their diets.
PMID- 28423511
TI - ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression
and autophagy.
AB - The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition
in cancer therapy is tempered by the identification of new emerging functions of
ATM, which suggests that the role of this protein in cancer progression is
complex. We recently demonstrated that this tumor suppressor gene could act as
tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2)
positive breast cancer. Herein we put in evidence that ATM expression sustains
the proportion of cells with a stem-like phenotype, measured as the capability to
form mammospheres, independently of HER2 expression levels. Transcriptomic
analyses revealed that, in mammospheres, ATM modulates the expression of cell
cycle-, DNA repair- and autophagy-related genes. Among these, the silencing of
the autophagic gene, autophagy related 4C cysteine peptidase (ATG4C), impairs
mammosphere formation similarly to ATM depletion. Conversely, ATG4C ectopic
expression in cells silenced for ATM expression, rescues mammospheres growth.
Finally, tumor array analyses, performed using public data, identify a
significant correlation between ATM and ATG4C expression levels in all human
breast cancer subtypes, except for the basal-like one.Overall, we uncover a new
connection between ATM kinase and autophagy regulation in breast cancer. We
demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of
mammosphere formation, suggesting that their targeting may improve current
approaches to eradicate breast cancer cells with a stem-like phenotype.
PMID- 28423512
TI - Kinase analysis of penile squamous cell carcinoma on multiple platforms to
identify potential therapeutic targets.
AB - Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly
understood biology and suboptimal systemic therapy. Given that kinases may be
drivers and readily actionable, we performed comprehensive multiplatform analysis
of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected
from 11 patients with PSCC. After macrodissection to demarcate tumor from normal
tissue, the samples underwent multiplatform analysis of kinases. Next Generation
Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture
and run on the Illumina MiSeq at PE150bp. The NanoString nCounter(r) platform
analyzed the expression of 519 kinase genes. Kinase activity of tissue lysates
was measured using PamStation(r)12 high-content phospho-peptide substrate
microarray system. Network mapping was done with GeneGo MetaCoreTM and upstream
kinase prediction was performed with BioNavigator and the Kinexus database.
Ingenuity pathway analysis was performed to integrate elevated kinase activity
and gene over-expression with coexisting missense mutations at DNA level. Top
pathways upregulated in both the kinase activity and gene expression platforms
were PTEN, STAT3, GNRH, IL-8 and B cell receptor signaling. Potentially relevant
missense mutations were seen in 176 kinase genes, with the top altered pathways
overlapping with gene overexpression being GNRH, NF-kB and STAT3 signaling.
ERBB2, ERBB3 and SYK were altered on NGS and also exhibited elevated kinase
activity. To summarize, multiplatform comprehensive analysis of kinases
discovered potential drivers of PSCC and actionable therapeutic targets.
Translational studies are necessary to validate the functional relevance of our
data to make advances in this rare malignancy.
PMID- 28423513
TI - miR-503-5p confers drug resistance by targeting PUMA in colorectal carcinoma.
AB - The development of multidrug-resistance (MDR) is a major contributor to death in
colorectal carcinoma (CRC). Here, we investigated the possible role of microRNA
(miR)-503-5p in drug resistant CRC cells. Unbiased microRNA array screening
revealed that miR-503-5p is up-regulated in two oxaliplatin (OXA)-resistant CRC
cell lines. Overexpression of miR-503-5p conferred resistance to OXA-induced
apoptosis and inhibition of tumor growth in vitro and in vivo through down
regulation of PUMA expression. miR-503-5p knockdown sensitized chemoresistant CRC
cells to OXA. Our studies indicated that p53 suppresses miR-503-5p expression and
that deletion of p53 upregulates miR-503-5p expression. Inhibition of miR-503-5p
in p53 null cells increased their sensitivity to OXA treatment. Importantly,
analysis of patient samples showed that expression of miR-503-5p negatively
correlates with PUMA in CRC. These results indicate that a p53/miR-503-5p/PUMA
signaling axis regulates the CRC response to chemotherapy, and suggest that miR
503-5p plays an important role in the development of MDR in CRC by modulating
PUMA expression.
PMID- 28423514
TI - Mitotic read-out genes confer poor outcome in luminal A breast cancer tumors.
AB - Luminal breast tumors have been classified into A and B subgroups, with the
luminal A being associated with a more favorable clinical outcome. Unfortunately,
luminal A tumors do not have a universally good prognosis. We used transcriptomic
analyses using public datasets to evaluate the differential expression between
normal breast tissue and breast cancer, focusing on upregulated genes included in
cell cycle function. Association of selected genes with relapse free survival
(RFS) and overall survival (OS) was performed using the KM Plotter Online Tool
(http://www.kmplot.com). Seventy-seven genes were differentially expressed
between normal and malignant breast tissue. Only five genes were associated with
poor RFS and OS. The mitosis-related genes GTSE1, CDCA3, FAM83D and SMC4 were
associated with poor outcome specifically in Luminal A tumors. The combination of
FAM83D and CDCA3 for RFS and GTSE1 alone for OS showed the better prediction for
clinical outcome. CDCA3 was amplified in 3.4% of the tumors, and FAM83D and SMC4
in 2.3% and 2.2%, respectively. In conclusion, we describe a set of genes that
predict detrimental outcome in Luminal A tumors. These genes may have utility for
stratification in trials of antimitotic agents or cytotoxic chemotherapy, or as
candidates for direct target inhibition.
PMID- 28423515
TI - Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual
PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma.
AB - Glioblastoma (GBM) is an ideal candidate disease for signal transduction targeted
therapy because the majority of these tumors harbor genetic alterations that
result in aberrant activation of growth factor signaling pathways. Loss of
heterozygosity of chromosome 10, mutations in the tumor suppressor gene PTEN, and
PI3K mutations are molecular hallmarks of GBM and indicate poor prognostic
outcomes in many cancers. Consequently, inhibiting the PI3K pathway may provide
therapeutic benefit in these cancers. PI3K inhibitors generally block
proliferation rather than induce apoptosis. To restore the sensitivity of GBM to
apoptosis induction, targeted agents have been combined with conventional
therapy. However, the molecular heterogeneity and infiltrative nature of GBM make
it resistant to traditional single agent therapy. Our objectives were to test a
dual PI3K/mTOR inhibitor that may cross the blood-brain barrier (BBB) and provide
the rationale for using this inhibitor in combination regimens to chemotherapy
induced synergism in GBM. Here we report the preclinical potential of a novel,
orally bioavailable PI3K/mTOR dual inhibitor, DS7423 (hereafter DS), in in-vitro
and in-vivo studies. DS was tested in mice, and DS plasma and brain
concentrations were determined. DS crossed the BBB and led to potent suppression
of PI3K pathway biomarkers in the brain. The physiologically relevant
concentration of DS was tested in 9 glioma cell lines and 22 glioma-initiating
cell (GIC) lines. DS inhibited the growth of glioma tumor cell lines and GICs at
mean 50% inhibitory concentration values of less than 250 nmol/L. We found that
PI3K mutations and PTEN alterations were associated with cellular response to DS
treatment; with preferential inhibition of cell growth in PI3KCA-mutant and PTEN
altered cell lines. DS showed efficacy and survival benefit in the U87 and GSC11
orthotopic models of GBM. Furthermore, administration of DS enhanced the
antitumor efficacy of temozolomide against GBM in U87 glioma models, which shows
that PI3K/mTOR inhibitors may enhance alkylating agent-mediated cytotoxicity,
providing a novel regimen for the treatment of GBM. Our present findings
establish that DS can specifically be used in patients who have PI3K pathway
activation and/or loss of PTEN function. Further studies are warranted to
determine the potential of DS for glioma treatment.
PMID- 28423516
TI - The addition of celecoxib improves the antitumor effect of cetuximab in
colorectal cancer: role of EGFR-RAS-FOXM1-beta- catenin signaling axis.
AB - Here we showed that the addition of the COX-2 inhibitor celecoxib improved the
antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR
antibody cetuximab. The addition of celecoxib augmented the efficacy of cetuximab
to inhibit cell proliferation and to induce apoptosis in CRC cells. Moreover, the
combination of celecoxib and cetuximab was more effective than either treatment
alone in reducing the tumor volume in a mouse xenograft model. The combined
treatment enhanced the inhibition of EGFR signaling and altered the subcellular
distribution of beta-catenin. Moreover, knockdown of FOXM1 showed that this
transcription factor participates in this enhanced antitumoral response. Besides,
the combined treatment decreased beta-catenin/FOXM1 interaction and reduced the
cancer stem cell subpopulation in CRC cells, as indicated their diminished
capacity to form colonospheres. Notably, the inmunodetection of FOXM1 in the
nuclei of tumor cells in human colorectal adenocarcinomas was significantly
associated with response of patients to cetuximab. In summary, our study shows
that the addition of celecoxib enhances the antitumor efficacy of cetuximab in
CRC due to impairment of EGFR-RAS-FOXM1-beta-catenin signaling axis. Results also
support that FOXM1 could be a predictive marker of response of mCRC patients to
cetuximab therapy.
PMID- 28423517
TI - Next generation sequencing of extraskeletal myxoid chondrosarcoma.
AB - Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated
soft tissue sarcoma with a high propensity for metastases. Using a clinical
sequencing approach, we genomically profiled patients with metastatic EMC to
elucidate the molecular biology and identify potentially actionable mutations. We
also evaluated potential predictive factors of benefit to sunitinib, a multi
targeted tyrosine kinase inhibitor with reported activity in a subset of EMC
patients. Between January 31, 2012 and April 15, 2016, six patients with EMC
participated in the clinical sequencing research study. High quality DNA and RNA
was isolated and matched normal samples underwent comprehensive next generation
sequencing (whole or OncoSeq capture exome of tumor and normal, tumor PolyA+ and
capture transcriptome). The expression levels of sunitinib targeted-kinases were
measured by transcriptome sequencing for KDR, PDGFRA/B, KIT, RET, FLT1, and FLT4.
The previously reported EWSR1-NR4A3 translocation was identified in all patient
tumors; however, other recurring genomic abnormalities were not detected. RET
expression was significantly greater in patients with EMC relative to other types
of sarcomas except for liposarcoma (p<0.0002). The folate receptor was
overexpressed in two patients. Our study demonstrated that similar to other
translocation-associated sarcomas, the mutational profile of metastatic EMC is
limited beyond the pathognomonic translocation. The clinical significance of RET
expression in EMC should be explored. Additional pre-clinical investigations of
EMC may help elucidate molecular mechanisms contributing to EMC tumorigenesis
that could be translated to the clinical setting.
PMID- 28423518
TI - A novel pathogenic splice acceptor site germline mutation in intron 14 of the APC
gene in a Chinese family with familial adenomatous polyposis.
AB - Familial adenomatous polyposis (FAP) is an autosomal dominant precancerous
condition, clinically characterized by the presence of multiple colorectal
adenomas or polyps. Patients with FAP has a high risk of developing colorectal
cancer (CRC) from these colorectal adenomatous polyps by the mean age of
diagnosis at 40 years. Germline mutations of the APC gene cause familial
adenomatous polyposis (FAP). Colectomy has recommended for the FAP patients with
significant polyposis. Here, we present a clinical molecular study of a four
generation Chinese family with FAP. Clinical diagnosis of FAP has been done
according to the phenotype, family history and medical records. Patient's blood
samples were collected and genomic DNA was extracted. In order to identify the
pathogenic mutation underlying the disease phenotype targeted next-generation
sequencing and confirmatory sanger sequencing has undertaken. Targeted next
generation sequencing identified a novel heterozygous splice-acceptor site
mutation [c.1744-1G>A] in intron 14 of APC gene, which is co-segregated with the
FAP phenotypes in the proband and amongst all the affected family members. This
mutation is not present in unaffected family members and in normal healthy
controls of same ethnic origin. According to the LOVD database for Chinese
colorectal cancer patients, in Chinese population, 60% of the previously reported
APC gene mutations causes FAP, are missense mutations. This novel splice-acceptor
site mutation causing FAP in this Chinese family expands the germline mutation
spectrum of the APC gene in the Chinese population.
PMID- 28423519
TI - Vitamin D and VDR in cancer cachexia and muscle regeneration.
AB - Low circulating levels of vitamin D were associated with decreased muscle
strength and physical performance. Along this line, the present study was aimed
to investigate: i) the therapeutic potential of vitamin D in cancer-induced
muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in
tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased
circulating vitamin D compared to control rats, while muscle vitamin D receptor
(VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression
increased after vitamin D administration, without exerting appreciable effects on
body weight and muscle mass.The effects of vitamin D on muscle cells were studied
in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly,
fusing only partially and forming multinucleated structures with aberrant shape
and low myosin heavy chain content. Vitamin D treatment resulted in VDR
overexpression and myogenin down-regulation. Silencing VDR expression in C2C12
cultures abrogated the inhibition of differentiation exerted by vitamin D
treatment.These data suggest that VDR overexpression in tumor-bearing animals
contributes to muscle wasting by impairing muscle regenerative program. In this
regard, attention should be paid when considering vitamin D supplementation to
patients affected by chronic pathologies where muscle regeneration may be
involved.
PMID- 28423520
TI - Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor
infiltrating lymphocytes in testicular germ cell tumors.
AB - PURPOSE: Testicular germ cell tumors (TGCTs) are nearly universally curable
malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative
in a small subgroup of patients. Previously, we showed that PD-L1 overexpression
is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes
(TILs) are prognostic in different types of cancer. This study aimed to evaluate
the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. RESULTS: PD-L1
positive TILs were found significantly more often in seminomas (95.9% of
patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%),
choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with
high infiltration of PD-L1 positive TILs (HS >= 160) had significantly better
progression-free survival (HR = 0.17, 95% CI 0.09 - 0.31, p = 0.0006) and overall
survival (HR = 0.08, 95% CI 0.04 - 0.16, p = 0.001) opposite to patients with
lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in
TGCTs. MATERIALS AND METHODS: Surgical specimens from 240 patients with primary
TGCTs were included into this translational study. The PD-1 and PD-L1 expression
on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti
PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted
histoscore (HS) method. CONCLUSIONS: The prognostic value of PD-L1 expressing
TILs in TGCTs was demonstrated for the first time.
PMID- 28423521
TI - Therapeutic sensitivity to Rac GTPase inhibition requires consequential
suppression of mTORC1, AKT, and MEK signaling in breast cancer.
AB - Rac GTPases have oncogenic roles in cell growth, survival, and migration. We
tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell
lines. EHT1864-induced growth inhibition was associated with dual inhibition of
the PI3K/AKT/mTORC1 and MEK/ERK pathways. Breast cancer cells harboring PIK3CA
mutations or HER2 overexpression were most sensitive to Rac inhibition,
suggesting that such oncogenic alterations link Rac activation with
PI3K/AKT/mTORC1 and MEK/ERK signaling. Interestingly, EHT1864 decreased
activation of the mTORC1 substrate p70S6K earlier than AKT inhibition, suggesting
that Rac may activate mTORC1/p70S6K independently of AKT. Comparison of the
growth-inhibitory profile of EHT1864 to 137 other anti-cancer drugs across 656
cancer cell lines revealed significant correlation with the p70S6K inhibitor PF
4708671. We confirmed that Rac complexes contain MEK1/2 and ERK1/2, but also
contain p70S6K; these interactions were disrupted by EHT1864. Pharmacokinetic
profiles revealed that EHT1864 was present in mouse plasma at concentrations
effective in vitro for approximately 1 h after intraperitoneal administration.
EHT1864 suppressed growth of HER2+ tumors, and enhanced response to anti-estrogen
treatment in ER+ tumors. Further therapeutic development of Rac inhibitors for
HER2+ and PIK3CA-mutant cancers is warranted.
PMID- 28423522
TI - PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.
AB - OBJECTIVE: Serine protease 3 (PRSS3) is an isoform of trypsinogen, and plays an
important role in the development of many malignancies. The objective of this
study was to determine PRSS3 mRNA and protein expression levels in invasive
ductal carcinoma of the breast and normal surrounding tissue samples. RESULTS:
Both PRSS3 mRNA and protein levels were significantly higher in invasive ductal
carcinoma of the breast tissues than in normal or benign tissues (all P < 0.05).
High PRSS3 protein levels were associated with patients' age, histological grade,
Her-2 expression level, ki-67 expression, and the 5.0-year survival rate. These
high protein levels are independent prognostic markers in invasive ductal
carcinoma of the breast. MATERIALS AND METHODS: We used real-time quantitative
polymerase chain reactions (N = 40) and tissue microarray immunohistochemistry
analysis (N = 286) to determine PRSS3 mRNA and protein expression, respectively.
PRSS3 protein levels in invasive ductal carcinoma of the breast tissues were
correlated with the clinical characteristics of patients with invasive ductal
carcinoma of the breast and their 5.0-year survival rate. CONCLUSIONS: PRSS3 acts
as an oncogene in invasive ductal carcinoma of the breast development and
progression. This finding implies that detection of PRSS3 expression can be a
useful prognosis marker and the targeting of PRSS3 can potentially represent a
new strategy for invasive ductal carcinoma of the breast treatment.
PMID- 28423523
TI - miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like
phenotype by activating Wnt/beta-catenin signalling.
AB - PURPOSE: To examine the role of miR-106b-5p in regulating the cancer stem-cell
like phenotype in clear cell renal cell carcinomas (ccRCC). EXPERIMENTAL DESIGN:
Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines
and patients specimens. A series of in vivo and in vitro assays were performed to
confirm the effect of miR-106b-5p on ccRCC stemness phenotype. RESULTS: ccRCC
cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss
of-function studies demonstrated that overexpression of miR-106b-5p in ccRCC
cells increased the spheres formation ability and the proportion of side
population cells. Ectopic expression of miR-106b-5p in ccRCC cells increased
tumour growth rates and the number of metastatic colonies in the lungs by using
an orthotopic kidney cancer model and a tail vein injection model, respectively.
Mechanistic studies revealed that, miR-106b-5p has an activating effect on
Wnt/beta-catenin signalling. miR-106p-5p overexpression simultaneously targets
multiple negative regulators of the Wnt/beta-catenin pathway, namely, LZTFL1,
SFRP1 and DKK2. In addition, we also confirmed that miR-106b-5p and its targets
expression correlates with the overall-survival of ccRCC patients from TCGA.
CONCLUSIONS: These findings suggest that miR-106b-5p mediates the constitutive
activation of Wnt/beta-catenin signalling, likely serving as a potential
therapeutic target for ccRCC.
PMID- 28423524
TI - Critically short telomeres and toxicity of chemotherapy in early breast cancer.
AB - Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy,
fatigue) compromises long-term administration. Preclinical data suggest that the
burden of critically short telomeres (< 3 kilobases, CSTs), but not average
telomere length by itself, accounts for limited tissue renewal and turnover
capacity. The impact of this parameter (which can be modified with different
therapies) in chemotherapy-derived toxicity has not been studied.Blood from 115
treatment-naive patients from a clinical trial in early HER2-negative breast
cancer that received weekly paclitaxel (80 mg/m2 for 12 weeks) either alone or in
combination with nintedanib and from 85 healthy controls was prospectively
obtained and individual CSTs and average telomere lenght were determined by HT Q
FISH (high-throughput quantitative FISH). Toxicity was graded according to NCI
common toxicity criteria for adverse events (NCI CTCAE V.4.0). The variable under
study was "number of toxic episodes" during the 12 weeks of therapy.The
percentage of CSTs ranged from 6.5%-49.4% and was directly associated with the
number of toxic events (R2 = 0.333; P < 0.001). According to a linear regression
model, each 18% increase in the percentage of CSTs was associated to one
additional toxic episode during the paclitaxel cycles; this effect was
independent of the age or treatment arm. Patients in the upper quartile (> 21.9%
CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019)
episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average
telomere length was unrelated to the incidence of side effects.The percentage of
CSTs, but not the average telomere size, is associated with weekly paclitaxel
derived toxicity.
PMID- 28423525
TI - The combination of circulating long noncoding RNAs AK001058, INHBA-AS1, MIR4435
2HG, and CEBPA-AS1 fragments in plasma serve as diagnostic markers for gastric
cancer.
AB - BACKGROUND: Suitable diagnostic markers for cancers are urgently required in
clinical practice. Long non-coding RNAs, which have been reported in many cancer
types, are a potential new class of biomarkers for tumor diagnosis. RESULTS: Five
lncRNAs, including AK001058, INHBA-AS1, MIR4435-2HG, UCA1 and CEBPA-AS1 were
validated to be increased in gastric cancer tissues. Furthermore, we found that
plasma level of these five lncRNAs were significantly higher in gastric cancer
patients compared with normal controls. By receiver operating characteristic
analysis, we found that the combination of plasma lncRNAs with the area under the
curve up to 0.921, including AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, is
a better indicator of gastric cancer than their individual levels or other lncRNA
combinations. Simultaneously, we found that the expression levels of a series of
MIR4435-2HG fragments are different in gastric cancer plasma samples, but most of
them higher than that in healthy control plasma samples. MATERIALS AND METHODS:
LncRNA gene expression profiles were analyzed in two pairs of human gastric
cancer and adjacent non-tumor tissues by microarray analysis. Nine gastric cancer
associated lncRNAs were selected and assessed by quantitative real-time
polymerase chain reaction in gastric tissues, and 5 of them were further analyzed
in gastric cancer patients' plasma. CONCLUSIONS: Our results demonstrate that
certain lncRNAs, such as AK001058, INHBA-AS1, MIR4435-2HG, and CEBPA-AS1, are
enriched in human gastric cancer tissues and significantly elevated in the plasma
of patients with gastric cancer. These findings indicate that the combination of
these four lncRNAs might be used as diagnostic or prognostic markers for gastric
cancer patients.
PMID- 28423526
TI - CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and
prognosis of Kazakh esophageal squamous cell carcinoma.
AB - M2 macrophages was domesticated by tumor microenvironment to produce some
angiogenic molecules and protease, facilitating angiogenesis and matrix
breakdown, promoting tumor invasive and metastasis. However, The function of M2
macrophages to progression of eophageal carcinoma, especially Kazakh esophageal
carcinoma is still dimness. This study aims to investigate M2 macrophages
correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and
the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163
and CD34 as the marker of M2 macrophages and endothelial cells, were used to
identify the M2 macrophages density and microvessel density, respectively.
Immunohistochemistry staining was evaluated the expression of MMP9. The number of
infiltrated CD163-positive M2 macrophages in tumor islets and stroma was
significantly higher than in cancer adjacent normal tissues. The increased of M2
macrophages and microvessel density were significantly correlated with more
malignant phenotypes including lymph node metastasis and clinical stage
progression. Meanwhile, the expression of MMP9 showed much higher level in
esophageal squamous cell carcinoma than that in cancer adjacent normal tissues,
and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was
significantly associated with age, depth of tumor invasion, lymph node
metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor
stroma was positively associated with microvessel density and the expression of
MMP9, and as an independent poorly prognostic factor for overall survival time of
Kazakh esophageal squamous cell carcinoma. These findings suggest the increased
number of M2 macrophages correlated with high expression of MMP9 and high
microvessel density may contribute to the tumor aggressiveness and angiogenesis,
promoting the progression of Kazakh esophageal squamous cell carcinoma.
PMID- 28423527
TI - HES1 promotes extracellular matrix protein expression and inhibits proliferation
and migration in human trabecular meshwork cells under oxidative stress.
AB - Glaucoma is the leading cause of irreversible blindness. The most prevalent form
of glaucoma is primary open-angle glaucoma (POAG). Oxidative stress is one of the
major pathogenic factors of the POAG, and can elicit molecular and functional
changes in trabecular meshwork cells, causing increased aqueous humor outflow
resistance and elevated intraocular pressure. However, the regulatory mechanisms
underlying oxidative stress-induced cell phenotypic changes remain elusive.
Herein, we exposed primary human trabecular meshwork cells to the oxidative
stress induced by 300 MUM H2O2 for 2 h, and found significantly up-regulated
expression of extracellular matrix proteins and a transcription factor, hairy and
enhancer of split-1 (HES1). The cell functions, including migration and
proliferation, were impaired by the oxidative stress. Furthermore, HES1 shRNA
abrogated the extracellular matrix protein up-regulation and rescued the
functional defects caused by the oxidative stress; conversely, HES1
overexpression resulted in the molecular and functional changes similar to those
induced by H2O2. These results suggest that HES1 promotes extracellular matrix
protein expression and inhibits proliferative and migratory functions in the
trabecular meshwork cells under oxidative stress, thereby providing a novel
pathogenic mechanism underlying and a potential therapeutic target to the POAG.
PMID- 28423528
TI - Level of FACT defines the transcriptional landscape and aggressive phenotype of
breast cancer cells.
AB - Although breast cancer (BrCa) may be detected at an early stage, there is a
shortage of markers that predict tumor aggressiveness and a lack of targeted
therapies. Histone chaperone FACT, expressed in a limited number of normal cells,
is overexpressed in different types of cancer, including BrCa. Recently, we found
that FACT expression in BrCa correlates with markers of aggressive BrCa, which
prompted us to explore the consequences of FACT inhibition in BrCa cells with
varying levels of FACT.FACT inhibition using a small molecule or shRNA caused
reduced growth and viability of all BrCa cells tested. Phenotypic changes were
more severe in "high- FACT" cells (death or growth arrest) than in "low-FACT"
cells (decreased proliferation). Though inhibition had no effect on the rate of
general transcription, expression of individual genes was changed in a cell
specific manner. Initially distinct transcriptional profiles of BrCa cells became
similar upon equalizing FACT expression. In "high-FACT" cells, FACT supports
expression of genes involved in the regulation of cell cycle, DNA replication,
maintenance of an undifferentiated cell state and regulated by the activity of
several proto-oncogenes. In "low-FACT" cells, the presence of FACT reduces
expression of genes encoding enzymes of steroid metabolism that are
characteristic of differentiated mammary epithelia.Thus, we propose that FACT is
both a marker and a target of aggressive BrCa cells, whose inhibition results in
the death of BrCa or convertion of them to a less aggressive subtype.
PMID- 28423529
TI - PIF* promotes brain re-myelination locally while regulating systemic inflammation
clinically relevant multiple sclerosis M.smegmatis model.
AB - Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis
(MS) is a demyelinating autoimmune disease with few clinical forms and uncertain
etiology. Current studies suggest that it is likely caused by infection(s)
triggering a systemic immune response resulting in antigen/non-antigen-related
autoimmune response in central nervous system (CNS). New therapeutic approaches
are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a
local and systemic immunity regulatory role. Synthetic PIF (PIF) duplicates
endogenous peptide's protective effect in pre-clinical autoimmune and
transplantation models. PIF protects against brain hypoxia-ischemia by directly
targeting microglia and neurons. In chronic experimental autoimmune encephalitis
(EAE) model PIF reverses paralysis while promoting neural repair. Herein we
report that PIF directly promotes brain re-myelination and reverses paralysis in
relapsing remitting EAE MS model. PIF crosses the blood-brain barrier targeting
microglia. Systemically, PIF decreases pro-inflammatory IL23/IL17 cytokines,
while preserving CNS-specific T-cell repertoire. Global brain gene analysis
revealed that PIF regulates critical Na+/K+/Ca++ ions, amino acid and glucose
transport genes expression. Further, PIF modulates oxidative stress, DNA
methylation, cell cycle regulation, and protein ubiquitination while regulating
multiple genes. In cultured astrocytes, PIF promotes BDNF-myelin synthesis
promoter and SLC2A1 (glucose transport) while reducing deleterious E2F5, and
HSP90ab1 (oxidative stress) genes expression. In cultured microglia, PIF
increases anti-inflammatory IL10 while reducing pro-inflammatory IFNgamma
expression. Collectively, PIF promotes brain re-myelination and neuroprotection
in relapsing remitting EAE MS model. Coupled with ongoing, Fast-Track FDA
approved clinical trial, NCT#02239562 (immune disorder), current data supports
PIF's translation for neurodegenerative disorders therapy.
PMID- 28423530
TI - Patterns of failure and clinical outcomes of definitive radiotherapy for cervical
esophageal cancer.
AB - PURPOSE: Because of the scarcity of cervical esophageal cancer (CEC), data for
this disease entity is limited. We aim to evaluate the outcomes, prognostic
factors and failure patterns of CEC treated by contemporary radiotherapy (RT).
METHODS: We retrospectively analyzed 86 CEC patients consecutively treated
between 2007 and 2015 by definitive RT with or without concurrent chemotherapy.
RT was mainly delivered with Intensity Modulated Irradiation Therapy (IMRT) or
Volumetric-Modulated Arc Therapy (VMAT). Statistical analyses were performed on
survival, prognostic factors and failure patterns. RESULTS: The median follow-up
time was 19.4 months. The 3-year overall survival (OS), local regional failure
free survival (LRFFS), distant metastatic free survival (DMFS), and progression
free survival (PFS) were 53.6%, 57.9%, 81.5% and 41.5%, respectively. Independent
predictors for poorer OS were N stage, hoarseness and recurrent laryngeal nerve
lymph node (RLN) involvement, and predictors for LRFFS were N stage and EQD2
(equivalent dose in 2 Gy fraction) to gross tumor volume (GTV), with >= 66Gy
achieving local control of 94.7%. Patients receiving elective nodal irradiation
(ENI) had better nodal regional control than those receiving involved field
irradiation (IFI). 31 (36%) patients had treatment failure and 15 (17.4%), 8
(9.3%) and 14 (16.2%) patients had local, regional, and distant failure,
respectively. 86.7% (13/15) local failures were within GTV, and supraclavicular
region (62.5%, 5/8) was the most common regional failure site. No severe
toxicities were observed. CONCLUSIONS: Our results seem to indicate that good
locoregional control might be achieved for CEC with adequate radiation dose and
treatment planning approaches.
PMID- 28423531
TI - Epigenetic inactivation of HOXA11, a novel functional tumor suppressor for renal
cell carcinoma, is associated with RCC TNM classification.
AB - Epigenetic inactivation of HOXA11, a putative tumor suppressor, is frequently
observed in a number of solid tumors, but has not been described in RCC (renal
cell carcinoma). In this study, we investigated the expression, epigenetic
changes and the function of HOXA11 in human renal cell carcinoma (RCC). HOXA11
was silenced or down-regulated in RCC cell lines and tissues. Methylation
specific PCR (MSP) and bisulfite genomic sequencing (BGS) revealed that the
HOXA11 promoter was hypermethylated in 5/6 RCC cell lines. Demethylation
treatment resulted in demethylation of the promoter and increased HOXA11
expression in these cell lines. HOXA11 methylation was also detected in 68/95
(70.5%) primary RCC tumors, but only rare adjacent non-malignant renal tissues
(13%, 3/23) showed hypermethylation of promoter. We also found that the
methylation of HOXA11 was associated with higher TNM classification of RCC
(p<0.05). Ectopic expression of HOXA11 led to significant inhibition of
proliferation, colony formation, migration and invasion abilities and induced RCC
cells apoptosis. Moreover, HOXA11 was found to inhibit Wnt signaling. Thus, our
study demonstrated that HOXA11 function as a tumor suppressor in RCC, while it is
frequently silenced by promoter methylation in RCC.
PMID- 28423532
TI - Implication of vascular endothelial growth factor A and C in revealing diagnostic
lymphangiogenic markers in node-positive bladder cancer.
AB - Several lymphangiogenic factors, such as vascular endothelial growth factors
(VEGFs), have been found to drive the development of lymphatic metastasis in
bladder cancer (BCa).Here, we have analyzed the gene expression of
lymphangiogenic factors in tissue specimens from 12 non-muscle invasive bladder
cancers (NMIBC) and 11 muscle invasive bladder cancers (MIBC), considering tumor
and tumor-adjacent normal bladder areas obtained from the same organs. We then
compared the results observed in patients with those obtained after treating
human primary bladder microvascular endothelial cells (MEC) with either direct
stimulation with VEGF-A or VEGF-C or by co-culturing (trans-well assay) MEC with
bladder cancer cell lines varying in VEGF-A and VEGF-C production based on tumor
grade.The genes of three markers of lymphatic endothelial commitment and
development (PDPN, LYVE-1 and SLP-76) were significantly overexpressed in tissues
of MIBC patients showing positive lymphovascular invasion (LVI+), lymph node
metastasis (Ln+) and tumor progression. Their expression was also significantly
enhanced either after direct stimulation of MEC by VEGF-A and VEGF-C or in the
trans-well assay with each bladder cancer cell line.SLP-76 showed the highest
gene expression. Both VEGF-A and VEGF-C also enhanced the expression of SLP-76
protein in MEC. However, a correlation between increase of SLP-76 gene expression
and the ability of MEC to migrate could only be seen after induction by VEGF
C.The significant expression of SLP-76 in LVI+/Ln+ progressive MIBC and its
overexpression in MEC after VEGF-A and VEGF-C stimulation suggest the need to
develop this regulator of developmental lymphangiogenesis as a diagnostic tool in
BCa.
PMID- 28423533
TI - SPC24 is critical for anaplastic thyroid cancer progression.
AB - In the past 2 decades, the incidence of thyroid cancer has been rapidly
increasing worldwide. Anaplastic thyroid cancer (ATC) is the most lethal of all
thyroid cancers and one of the most aggressive human carcinomas. SPC24 is an
important component of the mitotic checkpoint machinery in the tumorigenesis and
high levels of SPC24 have been found in colorectal and hepatocellular carcinomas,
but its role in anaplastic thyroid cancer is still unclear. Our results showed
that SPC24 was high expressed in human thyroid cancer samples. In addition,
knockingdown endogenous SPC24 could repress cell growth, inhibit cell invasive
ability and promote apoptosis in different ATC cells. Next, in vivo xenograft
studies indicated that the SPC24 knockdown cells has decreased tumor size
compared to the controls. This conclusion is also endorsed by our studies using
human thyroid cancer samples. Taken together, our data demonstrates that SPC24
can serve as a promising prognostic biomarker of ATC cells and it is a novel
strategy which could be developed by targeting SPC24 in future.
PMID- 28423534
TI - Estrogen deficiency is associated with hippocampal morphological remodeling of
early postmenopausal mice.
AB - Estrogen (E2) deficiency is reported to involve in the impairment of cognition in
postmenopausal women. However, the morphological basis is still unclear. In the
present study, using transmission electron microscopy (TEM), we observed the
ultrastructure of hippocampus in female C57BL/6 mice at the age of 18 months (18
M) which is considered as the early stage of postmenopause (n = 8). Compared with
control mice aged 6 M (n = 8), we identified that the morphological changes in
the hippocampus of these menopausal mice were mitochondrial damage, lipofuscin
deposition and microtubule degradation. Notably, after E2 was subcutaneously
injected into mice aged 16 M with a dosage of 3.5 MUg/kg every three days for two
months in the 18 M + E2 group (n = 8), mitochondrial damage and lipofuscin
deposition in the DG region of hippocampus were prevented, but the degraded
microtubules in the hippocampus of postmenopausal mice were failed to restore.
These data suggest that hippocampal ultrastructure remodeling in mice can be
initiated at the early stage of postmenopause, E2 supplementation could only have
an effect on mitochondrial damage and lipofuscin increase.
PMID- 28423535
TI - Overall survival with crizotinib and next-generation ALK inhibitors in ALK
positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide
cohort retrospective study.
AB - Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi)
crizotinib in a large population of unselected patients with ALK-positive non
small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with
crizotinib in unselected ALK-positive NSCLC patients and whether post-progression
systemic treatments affect survival outcomes.ALK-positive NSCLC patients
receiving crizotinib in French expanded access programs or as approved drug were
enrolled. We collected clinical and survival data, RECIST-defined progressive
disease (PD) and post-PD systemic treatment efficacy. We performed multivariable
analysis of OS from crizotinib initiation and PD under crizotinib.At time of
analysis, 209 (65.7%) of the 318 included patients had died. Median OS with
crizotinib was 16.6 months. The line of crizotinib therapy did not impact
survival outcomes. Of the 263 patients with PD, 105 received best supportive
care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation
ALKi. Next-generation ALKi treatment correlated with better survival outcomes in
multivariate analysis. These patients had a median post-PD survival of 25.0
months and median OS from metastatic disease diagnosis of 89.6 months.Unselected
ALK-positive NSCLC patients achieve good survival outcomes with crizotinib
therapy. Next-generation ALKi may provide survival improvement after PD under
crizotinib.
PMID- 28423536
TI - JMJD3 suppresses stem cell-like characteristics in breast cancer cells by
downregulation of Oct4 independently of its demethylase activity.
AB - Epigenetic regulator JMJD3 plays an important role in both tumor progression and
somatic cell reprogramming. Here, we explored the effect of JMJD3 on the stem
cell-like characteristics of breast cancer and its underlying mechanism involving
stemness-related transcription factor Oct4. Our data revealed that, in breast
cancer cells lines and an orthotopic xenograph mouse model of breast cancer,
ectopic overexpression of JMJD3 suppressed stem cell-like characteristics of
breast cancer cells, whereas knockdown of JMJD3 promoted these characteristics.
Oct4 mediated the suppressive effects of JMJD3 on the stemness of breast cancer
cells. The inhibitory effect of JMJD3 on Oct4 was independent of demethylase
activity, but mediated via degradation of PHF20. Furthermore, we applied an
agonist of the vitamin D receptor, paricalcitol, and found that it induced JMJD3
in breast cancer cells. Our data showed that administration of paricalcitol
suppressed stem cell-like characteristics and Oct4 expression. Taken together,
JMJD3 inhibits the stem cell-like characteristics in breast cancer by suppression
of stemness factor Oct4 in a PHF20-dependent manner. Administration of
paricalcitol leads to upregulation of JMJD3 that suppresses Oct4 expression and
the stem cell-like characteristics in breast cancer.
PMID- 28423537
TI - Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with
Ki67 in estrogen receptor-positive HER2-negative breast cancer.
AB - PAM50/Prosigna gene expression-based assay identifies three categorical risk of
relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal
patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative
(HER2-) early breast cancer. Low risk patients might not need adjuvant
chemotherapy since their risk of distant relapse at 10-years is below 10% with
endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2-
and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A
tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however,
the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0
10% group was 42.7% (with tumor sizes <=2 cm) and 33.9% (with tumor sizes > 2
cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or
ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low
risk outcome patients or Luminal A disease in the clinical setting is unreliable.
In the absence of a well-validated prognostic gene expression-based assay, the
optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A
disease remains at 14%.
PMID- 28423538
TI - Gene regulatory pattern analysis reveals essential role of core transcriptional
factors' activation in triple-negative breast cancer.
AB - BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer
subtype. Genome-scale molecular characteristics and regulatory mechanisms that
distinguish TNBC from other subtypes remain incompletely characterized. RESULTS:
By combining gene expression analysis and PANDA network, we defined three
different TF regulatory patterns. A core TNBC-Specific TF Activation Driven
Pattern (TNBCac) was specifically identified in TNBC by computational analysis.
The essentialness of core TFs (ZEB1, MZF1, SOX10) in TNBC was highlighted and
validated by cell proliferation analysis. Furthermore, 13 out of 35 co-targeted
genes were also validated to be targeted by ZEB1, MZF1 and SOX10 in TNBC cell
lines by real-time quantitative PCR. In three breast cancer cohorts, non-TNBC
patients could be stratified into two subgroups by the 35 co-targeted genes along
with 5 TFs, and the subgroup that more resembled TNBC had a worse prognosis.
METHODS: We constructed gene regulatory networks in breast cancer by Passing
Attributes between Networks for Data Assimilation (PANDA). Co-regulatory modules
were specifically identified in TNBC by computational analysis, while the
essentialness of core translational factors (TF) in TNBC was highlighted and
validated by in vitro experiments. Prognostic effects of different factors were
measured by Log-rank test and displayed by Kaplan-Meier plots. CONCLUSIONS: We
identified a core co-regulatory module specifically existing in TNBC, which
enabled subtype re-classification and provided a biologically feasible view of
breast cancer.
PMID- 28423539
TI - Interplay between DeltaNp63 and miR-138-5p regulates growth, metastasis and
stemness of oral squamous cell carcinoma.
AB - TP63 acts as a master regulator in epithelia development and in the progression
of various cancers, but its role in oral cancer pathogenesis remains unknown.
This study aimed to explore the role of TP63 in the progression of oral squamous
cell carcinoma (OSCC). This study shows that DeltaNp63, the predominant isoform
of TP63, is significantly upregulated in OSCC tissues and cell lines compared
with their normal counterparts, and its expression is closely correlated with
pathological differentiation, lymph node metastasis and clinical stage in
patients with OSCC. The overexpression of DeltaNp63 promotes growth, metastasis
and stem-like properties in OSCC cells, and DeltaNp63 depletion significantly
represses OSCC cellular phenotypes in vitro and in vivo. The DeltaNp63 isoform
transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p
expression partially abolishes the effect of upregulating DeltaNp63. This study
also demonstrates that miR-138-5p directly targets DeltaNp63, resulting in
crosstalk with DeltaNp63. The correlation between DeltaNp63 and miR-138-5p was
further validated in OSCC tissues and was found to be significantly associated
with the prognosis of patients with OSCC. Therefore, our data reveal that the
interplay between DeltaNp63 and miR-138-5p promotes OSCC progression by
regulating cell growth, metastasis and stemness.
PMID- 28423540
TI - Correlations between intravoxel incoherent motion (IVIM) parameters and
histological findings in rectal cancer: preliminary results.
AB - Our purpose was to correlate different intravoxel incoherent motion (IVIM),
histopathological and clinical parameters in rectal cancer. 17 patients with
histologically proven rectal cancer investigated on a 3.T device were included
into the study. DWI was performed using a multi-slice single-shot echo-planar
imaging sequence with b values of 0, 50, 200, 500 and 1000 s/mm.2 A polygonal
region of interest was drawn within the tumors on every b image. The following
parameters were retrieved from IVIM: apparent diffusion coefficient (ADC), true
diffusion (D), pseudo diffusion coefficient (D*), perfusion factor (f), and
relative perfusion f.D*. In every case, cell count, nucleic areas, proliferation
index KI 67, and microvessel density were estimated on histopathological
specimens. Pearson's correlation coefficient was used to analyze the association
between the parameters. ADC correlated well with KI 67 index and D tended to
correlate with cell count and KI 67. ADC and D tended to correlate with total
nucleic area. The perfusion factor f correlated well with stained vessel area,
total vessel area, and vessel count. D* and fD* correlated with mean vessel
diameter. Distant metastasized tumors had higher D* and fD* values. IVIM
parameter reflected different clinical and histopathological features in rectal
cancer.
PMID- 28423541
TI - RNA sequencing analysis reveals protective role of kruppel-like factor 3 in
colorectal cancer.
AB - The Kruppel-like factor (KLF) family of transcription factors plays an important
role in embryonic formation and cancer progression. This study was performed to
determine the clinical importance of the KLF family in colorectal cancer (CRC).
In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were
used to comprehensively study the role of the KLF family in CRC. The results were
then further validated using an in-house cohort (n=194). Univariate and
multivariate Cox proportional hazards models were used to assess the risk factors
for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence
interval [CI], 0.272-0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059-1.995;
P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030-1.494, P=0.023) were identified as
potential biomarkers in the univariate analysis, but after Cox proportional
hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230-0.831; P=0.012) was shown
to be independently predictive of overall survival in patients with CRC. This
finding was validated in our in-house cohort, which demonstrated that KLF3
expression was an independent predictor of both overall survival (HR, 0.628; 95%
CI, 0.342-0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317
0.697, P=0.016). KLF3 expression was inversely correlated with the N stage
(P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was
correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a
potential new predictor and therapeutic target for CRC. Further study is needed
for a more detailed understanding of the role of KLF3 in CRC.
PMID- 28423542
TI - DNA methylation intratumor heterogeneity in localized lung adenocarcinomas.
AB - Cancers are composed of cells with distinct molecular and phenotypic features
within a given tumor, a phenomenon termed intratumor heterogeneity (ITH).
Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas;
however, the nature of methylation ITH in lung cancers has not been well
investigated. In this study, we generated methylation profiles of 48 spatially
separated tumor regions from 11 localized lung adenocarcinomas and their matched
normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip
array. We observed methylation ITH within the same tumors, but to a much less
extent compared to inter-individual heterogeneity. On average, 25% of all
differentially methylated probes compared to matched normal lung tissues were
shared by all regions from the same tumors. This is in contrast to somatic
mutations, of which approximately 77% were shared events amongst all regions of
individual tumors, suggesting that while the majority of somatic mutations were
early clonal events, the tumor-specific DNA methylation might be associated with
later branched evolution of these 11 tumors. Furthermore, our data showed that a
higher extent of DNA methylation ITH was associated with larger tumor size
(average Euclidean distance of 35.64 (> 3cm, median size) versus 27.24 (<= 3cm),
p = 0.014), advanced age (average Euclidean distance of 34.95 (above 65) verse
28.06 (below 65), p = 0.046) and increased risk of postsurgical recurrence
(average Euclidean distance of 35.65 (relapsed patients) versus 29.03 (patients
without relapsed), p = 0.039).
PMID- 28423543
TI - MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down
regulating the expression of MCL-1.
AB - Cancer stem cells are considered as the cell population which is responsible for
chemoresistance and treatment failure in breast cancer patients. Therefore, it is
urgent to explore the mechanism by which cancer stem cells survive under the
treatment of chemotherapeutic drugs such as cisplatin. In this paper, we
demonstrated significant decrease of miR-519d in breast cancer stem cells by
quantitative RT-PCR analysis. Furthermore, we found the enforced expression of
miR-519d in T-47D-cancer stem cells significantly increased their sensitivity to
cisplatin through the apoptosis pathway. In addition, the gene of MCL-1, which is
a member of pro-apoptotic Bcl-2 family, was found to be the target of miR-519d in
T-47D-cancer stem cells. Our date demonstrated that enforced miR-519d expression
enhanced the cisplatin-induced apoptosis through the MCL-1 dependent mitochondria
pathway in breast cancer stem cells. Taken together, the present study suggests
that miR-519d reduces chemoresistance in breast cancer stem cells, and
understanding of miR-519d may be helpful for increasing the efficacy of
chemotherapy.
PMID- 28423544
TI - Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx
assay: better prognostic indicator than Hans algorithm.
AB - Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a
biomarker that can predict the outcome of treatments accurately. To assess the
prognostic significance of the cell-of-origin type for DLBCLs, we applied the
Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed
paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo
DLBCL, not otherwise specified. All patients were treated with rituximab plus
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first
line of chemotherapy. Based on the expression levels of Bcl-6, CD10, and MUM-1
measured by immunohistochemistry, cases were subdivided into germinal center B
cell (GCB) and non-GCB types according to the Hans algorithm. NanoString assay
was performed on 82 cases. The Lymph2Cx assay successfully classified 82 cases
into three categories: activated B-cell (ABC), GCB, and unclassified types. The
concordance rate between the Lymph2Cx assay and the Hans algorithm was 73.6%. The
Lymph2Cx-defined ABC type had significantly poorer outcomes compared with the GCB
type (5-year overall survival, GCB vs. ABC, 96.6% vs. 77.1%, P = 0.020; 5-year
disease-free survival, GCB vs. ABC, 96.6% vs. 79.2%, P = 0.018). In contrast, no
significant differences were observed in survival between the two patient
subgroups with DLBCL types classified by the Hans algorithm. The Lymph2Cx assay
is a robust, reliable method for predicting the outcome of patients with DLBCL
treated with R-CHOP chemotherapy.
PMID- 28423545
TI - Hobnail variant of papillary thyroid carcinoma: molecular profiling and
comparison to classical papillary thyroid carcinoma, poorly differentiated
thyroid carcinoma and anaplastic thyroid carcinoma.
AB - BACKGROUND: As a rare but aggressive papillary thyroid carcinoma (PTC) variant,
the genetic changes of hobnail variant of PTC (HVPTC) are still unclear. RESULTS:
The prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort.
73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were
successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven
mutation variant types were identified among 11 genes. BRAF V600E mutation was
the most common mutation, which is present in almost all HVPTC samples (16/17,
94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT
promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and
TP53 mutation are almost exclusively present among ATC and PDTC samples although
TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations
were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The
only patient who died of disease progression harbored concomitant TERT C228T
mutation, BRAF V600E mutation and TP53 mutation. METHODS: HVPTC cases were
identified from a group of 1062 consecutive surgical specimens diagnosed as PTC
between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to
investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC),
poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma
(ATC). CONCLUSION: As an aggressive variant of PTC, HVPTC has relatively specific
molecular features, which is somewhat different from both CPTC and ATC/PDTC and
may underlie its relatively aggressive behavior.
PMID- 28423546
TI - Tetraspanin 8 (TSPAN 8) as a potential target for radio-immunotherapy of
colorectal cancer.
AB - Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human
colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided
significant efficiency for immunotherapy in CRC pre-clinical models. We therefore
evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2.
Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was
restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with
111In or 177Lu with radiochemical purities >95%, specific activity ranging from
300 to 600 MBq/mg, and radioimmunoreactive fractions >80%. The biodistribution of
[111In]DOTA-Ts29.2 in nude mice bearing HT29 or SW480 CRC xenografts showed a
high specificity of tumor localization with high tumor/blood ratios (HT29: 4.3;
SW480-TSPAN8: 3.9 at 72h and 120h post injection respectively). Tumor-specific
absorbed dose calculations for [177Lu]DOTA-Ts29.2 was 1.89 Gy/MBq, establishing
the feasibility of using radioimmunotherapy of CRC with this radiolabeled
antibody. A significant inhibition of tumor growth in HT29 tumor-bearing mice
treated with [177Lu]DOTA-Ts29.2 was observed compared to control groups. Ex vivo
experiments revealed specific DNA double strand breaks associated with cell
apoptosis in [177Lu]DOTA-Ts29.2 treated tumors compared to controls. Overall, we
provide a proof-of-concept for the use of [111In/177Lu]DOTA-Ts29.2 that
specifically target in vivo aggressive TSPAN8-positive cells in CRC.
PMID- 28423547
TI - Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian
tumors: implications for HMGA2 expression.
AB - The High-mobility group AT-hook 2 protein (HMGA2) is involved in different
processes during tumorigenesis. High expression levels of HMGA2 are found in
various types of cancer, with recent studies highlighting the important role of
miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian
tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas)
analyzed for HMGA2 expression as well as the expression of two miRNAs targeting
this gene, let-7a and miR-30c. We also evaluated the expression of the fragile
histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to
be an enhancer of miR-30c expression and a repressor of let-7a, respectively.
HMGA2 was found expressed at high levels in most samples analyzed, with clear
cell carcinomas as the only exception. let-7a and miR-30c were highly deregulated
in all tumor types. LIN28A and FHIT were found overexpressed in all examined
tumor types. The chromosomal imbalances that might lead to loss of the genes
expressing let-7a and miR-30c could be evaluated on the basis of previously
generated karyotypic and high resolution comparative genomic hybridization (CGH)
data on 103 tumors. 76% of the samples with an imbalanced genome had at least one
chromosomal aberration leading to a deletion of a miRNA cluster for let-7a and
miR-30c. FISH using locus specific probes for these clusters validate the
aberrations at the gene level. Our study shows that genomic imbalances are
involved in miR-30c and let-7a deregulation. One can reasonably assume that
dysregulation of these miRNAs is a cause leading to HMGA2 upregulation in ovarian
tumors.
PMID- 28423548
TI - Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma.
AB - Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers.
LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D
binding to herpesvirus entry mediator on T cells) is a ligand that induces robust
anti-tumor immunity by enhancing the recruitment and activation of effector
immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T
lymphoma cells that stably overexpressed Axl also showed high expression of
LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT
expression was upregulated through activation of the PI3K/AKT signaling pathway
and transcriptional induction by Sp1. The lytic activity of cytotoxic T
lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition,
tumor volume and growth were markedly reduced due to enhanced apoptotic cell
death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed
upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral
infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl
bearing mice as compared to mock controls. These data strongly suggested that Axl
exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the
tumor microenvironment of T lymphoma.
PMID- 28423549
TI - HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde
trafficking route and forces cells to enter apoptosis.
AB - Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody
as a targeting module and fragment of Pseudomonas exotoxin A as an effector
(toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer
cells overexpressing HER2 receptor in vitro and on HER2-positive experimental
tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of
particular importance in the case of targeted therapeutic agent aimed at
personalizing treatment of disease in relation to molecular genetic
characteristics of each patient. After specific binding to HER2 on the cell
surface and clathrin-mediated endocytosis the immunotoxin passes through
retrograde trafficking route. During this route the immunotoxin molecule is
supposed to undergo enzymatic processing that ends in separation of C-terminal
and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally
active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed
by cell death via apoptosis.
PMID- 28423550
TI - Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins
in platelet-derived growth factor b signaling pathway.
AB - Gastric cancer is one of the most common cancers in Asian countries. Searching
for reliable biomarkers involving the development of gastric cancer is important
for clinical practice. Quantitative proteomics has become an important method
contributed to the discovery of novel diagnostic or therapeutic targets for the
management of cancer. Here, we identified differently expressed proteins in
gastric cancer and normal gastric tissues by using the high resolution mass
spectrometer. Among the total of 2280 identified proteins, 87 were differentially
expressed between gastric cancer and normal gastric tissues. Notably, several
significant proteins are in the PDGF-B signaling pathway, including
peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which
were validated by western blot. Furthermore, upstream regulators including PDGF
B, PDGFR-beta, Akt, eIF4E and p70s6K were found significantly increased in the
gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the
proliferation of gastric cancer cells in vitro. The administration of exogenous
PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B
knockdown cells. Taken together, our findings suggested that PDGF-B signaling
pathway plays an important role in the regulation of gastric cancer proliferation
and the inhibition of this pathway may be a potential approach for treatment of
gastric cancer.
PMID- 28423551
TI - Metabolic reprogramming of the premalignant colonic mucosa is an early event in
carcinogenesis.
AB - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related
mortality in the United States. There is an increasing need for the
identification of biomarkers of pre-malignant and early stage CRC to improve risk
stratification and screening recommendations. In this study, we investigated the
possibility of metabolic and mitochondrial reprogramming early in the pre
malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients
undergoing screening colonoscopy, and gene expression of metabolic and
mitochondrial markers were assessed using real time quantitative PCR. Validation
studies were performed in two different animal models of colon carcinogenesis:
Pirc rats and AOM-treated rats. RESULTS: We found evidence of a Warburg effect in
the normal-appearing rectal mucosa of patients harboring precancerous lesions
elsewhere in the colon compared to control patients, with a significant increase
in HIF1alpha, SLC2A1 (referred to as GLUT1), PKM2, and LDHA. We also found
evidence of early mitochondrial changes in the colorectal field of patients
harboring pre-cancerous lesions, with significantly increased mitochondrial gene
expression of DRP1 (fission), OPA1 (fusion), PGC1-alpha (biogenesis), UCP2
(uncoupling) and mtND1 (copy number). Similar results were observed in the two
different animal models. CONCLUSIONS: These results demonstrate for the first
time evidence of early Warburg-like metabolic changes as well as changes in
mitochondrial function, dynamics and mtDNA copy number in endoscopically normal
premalignant colorectal mucosal field. These findings provide an opportunity for
the development of metabolic biomarkers that could be used for improving
screening recommendations and risk-stratification. This also provides a potential
target for novel chemopreventive strategies in the pre-malignant colorectal
field.
PMID- 28423552
TI - Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with
avelumab, an anti-PD-L1 antibody.
AB - The combined therapeutic potential of an immunocytokine designed to deliver IL-12
to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts
the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple
murine tumor models. The murine version of the immunocytokine, NHS-muIL12,
consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with
two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA,
NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer
plasma half-life and better antitumor efficacy against murine tumors than
recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN
gammaa??dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which
could be construed as an immunosuppressive action. Yet concurrent therapy with
NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor
effects in PD-L1a??expressing subcutaneously transplanted tumors (MC38, MB49) and
in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with
(a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and
(b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations.
These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody
enhances T cell activation and T cell effector functions within the tumor
microenvironment, significantly improving overall tumor regression. These results
should provide the rationale to examine the combination of these agents in
clinical studies.
PMID- 28423554
TI - uPAR directed-imaging of head-and-neck cancer.
PMID- 28423553
TI - Low vitamin D status is associated with inflammation in patients with prostate
cancer.
AB - Vitamin D deficiency has been associated with increased risks of prostate cancer.
Nevertheless, the mechanisms remain unclear. The aim of this study was to analyze
the association among prostate cancer, vitamin D status and inflammation. Sixty
patients with newly diagnosed prostate cancer and 120 age-matched controls were
recruited for this study. Vitamin D status was evaluated and serum inflammatory
molecules were measured. Serum 25-(OH)D was lower in patients with prostate
cancer. Moreover, serum 25(OH)D was lower in patients with severe prostate cancer
than patients with mild and moderate prostate cancer. By contrast, serum C
reactive protein (CRP) and interleukin (IL)-8, two inflammatory molecules, were
elevated in patients with prostate cancer. Serum 25-(OH)D was negatively
correlated with serum CRP and IL-8 in patients with prostate cancer. Additional
analysis showed that the percentage of vitamin D receptor positive nucleus in the
prostate was reduced in patients with prostate cancer. By contrast, the
percentage of nuclear factor kappa B p65-positive nucleus was elevated in
patients with prostate cancer. Our results provide evidence that there is an
association among prostate cancer, vitamin D deficiency and inflammatory
signaling. Inflammation may be an important mediator for prostate cancer
progression in patients with low vitamin D status.
PMID- 28423555
TI - HSP90 proteins in the scenario of tumor complexity.
PMID- 28423556
TI - Unwanted acquired mutations in Ba/F3 transformation assays.
PMID- 28423557
TI - Correction: Protective role of p53 in skin cancer: Carcinogenesis studies in mice
lacking epidermal p53.
PMID- 28423558
TI - Biological basis and clinical study of glycogen synthase kinase- 3beta-targeted
therapy by drug repositioning for glioblastoma.
AB - BACKGROUND: Glycogen synthase kinase (GSK)-3beta has emerged as an appealing
therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic
effect of the current approved drugs against GBM via inhibition of GSK3beta
activity both, in experimental setting and in a clinical study for recurrent GBM
patients by repositioning existent drugs in combination with temozolomide (TMZ).
MATERIALS AND METHODS: Progression-free and overall survival rates were compared
between patients with low or high expression of active GSK3beta in the primary
tumor. GBM cells and a mouse model were examined for the effects of GSK3beta
inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and
efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ
were tested in the mouse model and in a clinical study for recurrent GBM
patients. RESULTS: Activation of GSK3beta in the tumor inversely correlated with
patient survival as an independent prognostic factor. CLOVA cocktail
significantly inhibited cell invasion and proliferation. The patients treated
with CLOVA cocktail in combination with TMZ showed increased survival compared to
the control group treated with TMZ alone. CONCLUSIONS: Repositioning of the
GSK3beta-inhibitory drugs improved the prognosis of refractory GBM patients with
active GSK3beta in tumors. Combination of CLOVA cocktail and TMZ is a promising
approach for recurrent GBM.
PMID- 28423559
TI - Rottlerin as a novel chemotherapy agent for adrenocortical carcinoma.
AB - Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy
with a generally poor clinical outcome. There is no effective therapy for
advanced and metastatic ACC. In our study, we found that an existing drug
(rottlerin) exerted its tumour-suppressive function in ACC. Specifically,
rottlerin inhibited cellular proliferation of ACC cell lines (NCI-H295R and SW
13) in a dose- and time-dependent manner. We also found that rottlerin induced
cell apoptosis and promoted G0/G1 cell cycle arrest in ACC cell lines. The
cellular migration and invasion of ACC cell lines were decreased after treatment
with rottlerin. Further, the molecular expression of lipoprotein receptor related
protein 6 (LRP6) and beta-catenin were down-regulated in rottlerin-treated ACC
cells, which indicated that Wnt/beta-catenin signaling was involved in the tumour
suppressive function of rottlerin. To further confirm the anti-tumour function of
rottlerin, a nude mouse ACC xenograft model was used. The xenograft growth curves
and TUNEL assays demonstrated that rottlerin inhibited proliferation and induced
apoptosis in the ACC xenograft model. Furthmore, we verified that rottlerin down
regulated the expression of LRP6 and beta-catenin in vivo. The ACC cell line and
xenograft mouse model data indicated that rottlerin significantly inhibited
proliferation and induced apoptosis of ACC cells, likely via suppression of the
Wnt/beta-catenin signaling pathway. Our study indicated the potential therapeutic
utility of rottlerin as a novel and potential chemotherapeutic agent for ACC.
PMID- 28423560
TI - Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-kappaB and
activating Nrf2 signaling pathways.
AB - Geraniin, a typical ellagitannin isolated from Phyllanthusurinaria Linn, has been
reported to have anti-inflammatory effect. The aim of the study is to investigate
the therapeutic effects of geraniin on LPS-induced acute lung injury (ALI) in
mice. The mice were intranasal adminisration of LPS for 12 h. Geraniin was intra
peritoneal injection 1 h after LPS treatment. The results showed that geraniin
significantly attenuated LPS-induced pathological changes in the lung. Geraniin
also inhibited LPS-induced macrophages and neutrophils infiltration in the lung.
Geraniin significantly attenuated LPS-induced elevation of MPO level. LPS-induced
TNF-alpha, IL-6 and IL-1beta production were markedly suppressed by treatment of
geraniin. Furthermore, geraniin inhibited NF-kappaB activation in LPS-induced
ALI. In addition, geraniin was found to up-regulate the expression of Nrf2 and HO
1. In conclusion, these data suggested that geraniin had therapeutic effects in
LPS-induced ALI by inhibiting NF-kappaB and activating Nrf2 signaling pathways.
PMID- 28423561
TI - Dermis, acellular dermal matrix, and fibroblasts from different layers of pig
skin exhibit different profibrotic characteristics: evidence from in vivo study.
AB - To explore the profibrotic characteristics of the autografted dermis, acellular
dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin,
93 wounds were established on the dorsa of 7 pigs. 72 wounds autografted with the
superficial/deep dermis and acellular dermal matrix served as the
superficial/deep dermis and acellular dermal matrix group, respectively, and were
sampled at 2, 4, and 8 weeks post-wounding. 21 wounds autografted with/without
superficial/deep dermal fibroblasts served as the superficial/deep dermal
fibroblast group and the control group, respectively, and were sampled at 2 weeks
post-wounding. The hematoxylin and eosin staining showed that the wounded skin
thicknesses in the deep dermis group (superficial acellular dermal matrix group)
were significantly greater than those in the superficial dermis group (deep
acellular dermal matrix group) at each time point, the thickness of the cutting
plane in the deep dermal fibroblast group was significantly greater than that in
the superficial dermal fibroblast group and the control group. The western blots
showed that the alpha-smooth muscle actin expression in the deep dermis group
(superficial acellular dermal matrix group) was significantly greater than that
in the superficial dermis group (deep acellular dermal matrix group) at each time
point. In summary, the deep dermis and dermal fibroblasts exhibited more
profibrotic characteristics than the superficial ones, on the contrary, the deep
acellular dermal matrix exhibited less profibrotic characteristics than the
superficial one.
PMID- 28423562
TI - Circulating tumor cells in early stage lung adenocarcinoma: a case series report
and literature review.
AB - PURPOSE: The study aimed to monitor circulating tumor cells (CTCs) in early stage
lung adenocarcinoma patients. RESULTS: CTCs were characterized and classified to
epithelial (E-) CTCs, mesenchymal (M-) CTCs and epithelial- mesenchymal (E&M-)
CTCs, as per epithelial-mesenchymal transition(EMT) biomarkers. CTCs could not be
found in healthy controls. However, in cohort A, CTCs were found in 17 (17/18)
cases. Detection rate of E-CTCs was lower (5/18) compared with M-CTC (10/18) or
E&M-CTC (14/18). Highly abundant M-CTCs were prone to being in the tumors > 2 cm.
In cohorts A and B, CTCs count increased significantly in all patients with tumor
progression (7/7). Higher CTCs level or change range could be found
postoperatively in the patients with tumor progression, as compared with patients
with disease free survival (P < 0.01). Additionally, CTCs detected by CanPatrolTM
could be validated by CytoploRare or Pep@MNPs. MATERIALS AND METHODS: We included
four cohorts of patients and 20 healthy controls. In cohort A, CTCs were detected
by a newly established approach, i.e., CanPatrolTM, prior to anesthesia and
monitored after operation longitudinally. In cohort B, CTCs were not assessed
prior to operation, but were longitudinally detected after operation. For
validation, we detected FOLR(+)-CTCs by using CytoploRare and EPCAM(+)-CTCs by
using Pep@MNPs prior to operation, in cohorts C and D, respectively. CONCLUSION:
CTCs can be detected in early stage lung adenocarcinoma, even in adenocarcinoma
in situ, and CTCs detection can effectively monitor tumor progression. The
distinguishing of biomarkers of highly invasive and aggressive CTCs warrants
further robust study.
PMID- 28423563
TI - Regulation of p53wt glioma cell proliferation by androgen receptor-mediated
inhibition of small VCP/p97-interacting protein expression.
AB - The incidence of glioma in men is higher than that in women; however, little is
known about the expression and basic function of the androgen receptor (AR) in
gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the
transcriptional level was previously reported. The present study shows that the
protein level of AR is highly expressed in cell lines of the nervous system.
Moreover, the AR expression is increased while SVIP expression is decreased in
tumor tissue of glioma patients, which is in agreement with the progressing WHO
grades. A statistically significant increase in serum testosterone level of
glioma patients compared with that of non-cancer patients was also detected.
Furthermore, it has been proved that SVIP is down-regulated as well as AR is up
regulated in glioma cell lines with R1881 treatment. Interestingly, the depletion
of SVIP using siRNA facilitated cell proliferation and decreased p53 expression.
In addition, overexpression of SVIP increased cell death only in p53wt cell
lines. Moreover, U87MG cells, p53wt cell line was susceptible to AR antagonists
in vitro and in vivo. The current study provides insight into the biological role
of AR in suppressing SVIP and p53 and promoting the progression of glioma as well
as the clinical treatment of glioma patients.
PMID- 28423564
TI - Hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by
activating Akt and Erk in gastric cancer.
AB - CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone
morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II
(BMPR II), which mediates extracellular to intracellular signal transmission and
is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1
expression was significantly down-regulated in gastric cancer tissues and
associated with poor survival. Clinic-pathological parameters demonstrated a
close relationship between low CHRDL1 expression and metastasis. In vitro, CHRDL1
knockdown promoted tumor cell proliferation and migration through BMPR II by
activating Akt, Erk and beta-catenin. Furthermore, we observed the
hypermethylation of the CHRDL1 promoter in gastric cancer, which induced low
expression of CHRDL1 and decreased its secretion to the supernatant. Finally, in
vivo experiments confirmed that CHRDL1 acted as a tumor suppressor gene in
suppressing tumor growth and metastasis.
PMID- 28423565
TI - Identification and characterization of L1-specific endo-siRNAs essential for
early embryonic development in pig.
AB - Small noncoding RNAs (sncRNAs) play important roles in RNA interference (RNAi).
In addition to microRNA (miRNA) and Piwi-interacting RNA (piRNA), one key member
of sncRNAs group is endogenous small interfering RNA (endo-siRNA). Some studies
do show the role of endo-siRNAs in Dicer and/or Ago mutants, however, the
biological functions of specific endo-siRNAs remains mostly unanswered. In the
study, we have performed a comparative analysis of endo-siRNAs present in porcine
sperms, oocytes and zygotes, identified by deep sequencing and bioinformatics
analysis. Further, we observe a large amount of endo-siRNAs specific binding on
ORF2 and 3' UTR of porcine L1 (L1-siRNAs). And, 9 L1-siRNAs generated from a
dsRNA formed between L1 transcript and a newly identified an antisense noncoding
RNA was characterized. We show the L1-siRNAs regulate early embryonic development
by inhibiting the activity of L1 retrotransposition. This work can contribute to
understanding the functional role of abundant endo-siRNAs in embryonic
development.
PMID- 28423566
TI - The diagnostic role of microRNA-34a in breast cancer: a systematic review and
meta-analysis.
AB - BACKGROUND: MicroRNA-34a (miR-34a) is a master regulator of tumor suppression in
breast cancer (BC). This systematic review aims to analyze the diagnostic
accuracy of miR-34a in the detection of BC as a biomarker. RESULTS: A total of
1858 BC cases and 494 controls from thirteen eligible studies reported in 9
publications were included. The overall pooled sensitivity, specificity, negative
likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds
ratio (DOR) were 85.50% (95% CI: 83.80-87.00%), 70.00% (95% CI: 65.80-74.10%),
0.29 (95% CI: 0.19-0.43), 2.58 (95% CI: 1.91-3.43), and 9.39 (95% CI: 5.47
16.12), respectively. Similarly, the overall area under the curve (AUC) of the
summary receiver operating characteristic (SROC) was 0.80, indicating the high
conservation of miR-34a as a biomarker. Furthermore, subgroup analysis suggested
that the use of miR-34a as a biomarker is more accurate in tissue-based sample of
invasive BC. We also indicated that miR-34a is a capable biomarker in diagnosing
BC in people of Caucasian descent. MATERIALS AND METHODS: A systematic search was
conducted for eligible publications that address miR-34a expression level in BC
cases and noncancerous controls. Diagnostic capacity of miR-34a for BC was
assessed using pooled sensitivity and specificity, DOR, and AUC of SROC. PLR and
NLR were verified to estimate the miR-34a diagnostic accuracy in clinical level.
The quality of the included studies was assessed by QUADAS-2. CONCLUSIONS: These
findings suggest miR-34a is a promising non-invasive biomarker in diagnosing BC.
Well-designed cohort studies should be implemented to warrant the diagnostic
value of miR-34a in clinical purposes.
PMID- 28423567
TI - CXCR1/2 pathways in paclitaxel-induced neuropathic pain.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a type of neuropathic pain
that represents a frequent and serious consequence of chemotherapy agents. Over
the last years, significant progress has been achieved in elucidating the
underlying pathogenesis of CIPN. The interference of taxanes with microtubule has
been proposed as a mechanism that leads to altered axonal transport and to
permanent neurological damages. The inflammatory process activated by
chemotherapeutic agents has been considered as a potential trigger of nociceptive
process in CIPN.In this study we investigated the effect of reparixin, an
inhibitor of CXCR1/CXCR2, in suppressing the development of paclitaxel-induced
nociception in rats. Moreover, reparixin activity in reversing the neurotoxic
effects induced by paclitaxel or GRO/KC in F11 cells was also analyzed.Reparixin
administered by continuous infusion ameliorated paclitaxel-induced mechanical and
cold allodynia in rats. In F11 cells, reparixin was able to inhibit the increase
of acetyladed alpha-tubulin induced both by paclitaxel and GRO/KC. The subsequent
experiments were performed in order to dissect the signal transduction pathways
under GRO/KC control, eventually modulated by paclitaxel and/or reparixin. To
this aim we found that reparixin significantly counteracted p-FAK, p-JAK2/p
STAT3, and PI3K-p-cortactin activation induced either by paclitaxel or
GRO/KC.Overall the present results have identified IL-8/CXCR1/2 pathway as a
mechanism involved in paclitaxel-induced peripheral neuropathy. In particular,
the obtained data suggest that the inhibition of CXCR1/2 combined with standard
taxane therapy, in addition to potentiating the taxane anti-tumor activity can
reduce chemotherapy-induced neurotoxicity, thus giving some insight for the
development of novel treatments.
PMID- 28423568
TI - Sepia ink oligopeptide induces apoptosis and growth inhibition in human lung
cancer cells.
AB - Sepia ink oligopeptide (SIO), as a tripeptide extracted from Sepia ink, could be
used as an inducer of apoptosis in human prostate cancer cells. We designed a
cyclo-mimetic peptide of SIO by introducing a disulfide bond to stabilize the
native peptide into beta turn structure, and produced a peptide with higher cell
permeability and stability. Through labeling an FITC to the N-terminus of the
peptide, the cell permeability was examined. Stabilized peptide showed enhanced
cellular uptake than linear tripeptide as indicated by flow cytometry and cell
fluorescent imaging. The high intracellular delivery of stable SIO could more
efficiently inhibit cell proliferation and induce apoptosis. Furthermore, the
expression of the anti-apoptotic protein Bcl-2 was down-regulated, whereas pro
apoptotic proteins P53 and caspase-3 were up-regulated by stable SIO. In
conclusion, our study is the first to use stable SIO to induce apoptosis in two
lung cancer cells A549 and H1299.
PMID- 28423569
TI - Accurate prediction of protein-protein interactions by integrating potential
evolutionary information embedded in PSSM profile and discriminative vector
machine classifier.
AB - Identification of protein-protein interactions (PPIs) is of critical importance
for deciphering the underlying mechanisms of almost all biological processes of
cell and providing great insight into the study of human disease. Although much
effort has been devoted to identifying PPIs from various organisms, existing high
throughput biological techniques are time-consuming, expensive, and have high
false positive and negative results. Thus it is highly urgent to develop in
silico methods to predict PPIs efficiently and accurately in this post genomic
era. In this article, we report a novel computational model combining our newly
developed discriminative vector machine classifier (DVM) and an improved Weber
local descriptor (IWLD) for the prediction of PPIs. Two components, differential
excitation and orientation, are exploited to build evolutionary features for each
protein sequence. The main characteristics of the proposed method lies in
introducing an effective feature descriptor IWLD which can capture highly
discriminative evolutionary information from position-specific scoring matrixes
(PSSM) of protein data, and employing the powerful and robust DVM classifier.
When applying the proposed method to Yeast and H. pylori data sets, we obtained
excellent prediction accuracies as high as 96.52% and 91.80%, respectively, which
are significantly better than the previous methods. Extensive experiments were
then performed for predicting cross-species PPIs and the predictive results were
also pretty promising. To further validate the performance of the proposed
method, we compared it with the state-of-the-art support vector machine (SVM)
classifier on Human data set. The experimental results obtained indicate that our
method is highly effective for PPIs prediction and can be taken as a
supplementary tool for future proteomics research.
PMID- 28423570
TI - Identification of long non-coding RNAs GAS5, linc0597 and lnc-DC in plasma as
novel biomarkers for systemic lupus erythematosus.
AB - Despite increasing evidence that long non-coding RNAs (lncRNAs) widely take part
in human diseases, the role of lncRNAs in systemic lupus erythematosus (SLE) is
largely unknown. In this study, we performed a two-stage study to explore the
plasma levels of five lncRNAs (GAS5, linc0949, linc0597, HOTAIRM1 and lnc-DC) and
their potential as SLE biomarkers. Compared with healthy controls, plasma levels
of GAS5 and lnc-DC were significantly decreased (P < 0.001 and P = 0.002,
respectively) while linc0597 were overexpressed in SLE patients (P < 0.001). When
SLE patients were divided into SLE without nephritis and lupus nephritis (LN),
the levels of lnc-DC were significantly higher in LN compared with SLE without
nephritis (P = 0.018), but no significant difference in levels of GAS5 and
linc0597 were found between LN and SLE without nephritis; plasma linc0949 level
showed no significant difference in all comparisons. Further evaluation on
potential biomarkers showed that GAS5, linc0597 and lnc-DC may specifically
identify patients with SLE, the combination of GAS5 and linc0597 provided better
diagnostic accuracy; lnc-DC may discriminate LN from SLE without nephritis. In
summary, GAS5, linc0597 and lnc-DC in plasma could be potential biomarkers for
SLE.
PMID- 28423571
TI - Predictive analysis of long non-coding RNA expression profiles in diffuse large B
cell lymphoma.
AB - Long non-coding RNAs (lncRNAs) are implicated in many tumors. To find novel
targets for study of diffuse large B-cell lymphoma (DLBCL), our team performed
genome-wide analyses of lncRNA expression in 5 DLBCL cell lines using the 4*180K
Agilent lncRNA Chip system, and in normal B cells. Five lncRNAs were validated by
quantitative reverse transcription polymerase chain reaction. The differentially
expressed lncRNAs and mRNAs were identified via false discovery rate and fold
change filtering. Potential targets correlated with DLBCL were recognized via
gene ontology and pathway analysis. Establishment of the co-expression network
was done using Cytoscape. In total, 1053 lncRNAs and 4391 mRNAs were dysregulated
in DLBCL cells, being comparing with normal B cells. The results suggested that
the expressions of the 5 lncRNAs were consistent with the chip results. Several
terms including the cell cycle, apoptosis, B cell receptor and NF-kappaB
signaling pathways were important in the progression of DLBCL. The chromosome
locations of a few lncRNAs and the associated coexpressed genes were demonstrated
by cis-regulatory gene analyses. The results of trans-analyses showed that
multiple transcription factors regulated lncRNA and gene expression. Those
outstanding lncRNAs in each group were implicated in the regulation of the TF
lncRNA-target gene network. Our study identified a set of lncRNAs differentially
expressed in DLBCL cells.
PMID- 28423572
TI - Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific
marker of breast and colorectal cancer.
AB - Changes in blood epigenetic age have been associated with several pathological
conditions and have recently been described to anticipate cancer development. In
this work, we analyze a publicly available leukocytes methylation dataset to
evaluate the relation between DNA methylation age and the prospective development
of specific types of cancer. We calculated DNA methylation age acceleration using
five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and
two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the
EPIC-Italy project and we compared 424 samples that remained cancer-free over the
approximately ten years of follow-up with 235 and 166 subjects who developed
breast and colorectal cancer, respectively. We show that the epigenetic age
estimated from blood DNA methylation data is statistically significantly
associated to future breast and male colorectal cancer development. These results
are corroborated by survival analysis that shows significant association between
age acceleration and cancer incidence suggesting that the chance of developing
age-related diseases may be predicted by circulating epigenetic markers, with a
dependence upon tumor type, sex and age estimator. These are encouraging results
towards the non-invasive and perspective usage of epigenetic biomarkers.
PMID- 28423573
TI - Involvement of AF1q/MLLT11 in the progression of ovarian cancer.
AB - The functional role of AF1q/MLLT11, an oncogenic factor involved in a
translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been
investigated in hematological and solid malignancies and its expression was found
to be linked to tumor progression and poor clinical outcome. In addition to its
oncogenic function, AF1q has been shown to play a role in the onset of basal and
drug-induced apoptosis in cancer cells of different histotypes, including ovarian
cancer. Through in vitro, ex vivo, and in silico approaches, we demonstrated here
that AF1q is also endowed with protumorigenic potential in ovarian cancer. In
ovarian cancer cell lines, stable AF1q overexpression caused activation of
epithelial-to-mesenchymal transition and increased motility/migratory/invasive
abilities accompanied by gene expression changes mainly related to Wnt signaling
and to signaling pathways involving in ERK/p38 activation. The potential role of
AF1q in ovarian cancer progression was confirmed by immunohistochemical and in
silico analyses performed in ovarian tumor specimens which revealed that the
protein was absent in normal ovarian epithelium and became detectable when
atypical proliferation was present. Moreover, AF1q was significantly lower in
borderline ovarian tumors (i.e., tumors of low malignant potential without
stromal invasion) than in invasive tumors, thus corroborating the association
between high AF1q expression and increased migratory/invasive cell behavior and
confirming its potential role in ovarian cancer progression. Our findings
demonstrated, for the first time, that AF1q is endowed with protumorigenic
activity in ovarian cancer, thus highlighting a dual behavior (i.e.,
protumorigenic and proapoptotic functions) of the protein in the malignancy.
PMID- 28423574
TI - Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular
carcinoma.
AB - Drug resistance to sorafenib is common in patients with hepatocellular
carcinoma(HCC). We examined the effects of a combination of sorafenib and
fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced
apoptosis and reduced cellular viability in HCC more effectively than either drug
alone. The combination treatment also inhibited activation of hepatic stellate
cells, whereas single drug treatments did not. On a molecular level, combined
treatment inhibited activation of the MAPK and NF-kappaB pathways via Toll-like
receptor 4 in HCC cells. Combined treatment also inhibited expression of stromal
cell-derived factor 1alpha in HCC cells, which further inhibited the MAPK pathway
in hepatic stellate cells. These results suggest that a combination of sorafenib
and fluvastatin may be a promising therapeutic strategy for patients with
advanced HCC.
PMID- 28423575
TI - Activated Notch signaling augments cell growth in hepatocellular carcinoma via up
regulating the nuclear receptor NR4A2.
AB - Hepatocellular carcinoma (HCC) is one of the most malignant cancers. Conventional
therapies are limited due to the human liver being such a unique organ and easily
showing side-effects. The unclear molecular mechanisms are tough challenges for
scientists searching for new and effective anti-HCC targeting drugs. We
identified that the nuclear receptor NR4A2 is a novel oncogene in HCC
progression. In this study, we show that NR4A2 and the notch recceptor Notch1
were expressed highly in primary HCC tissues and immortal HCC cells by using
qPCR, western blot and immuno-histochemistry assays. Both genes were observed to
stimulate HCC cell proliferation, anti-apoptosis and cell cycle arrest by using
cell proliferation assays and FACS assays. We also observed that the four notch
receptor subtypes (Notch1-4) displayed different effects on HCC cell growth. The
over-expression of Notch1 by transiently transfecting the intracellular domain of
Notch1 (ICN1, Notch1 active form) increased the expression of NR4A2, with the
knockdown of Notch1 decreasing NR4A2. This indicates that NR4A2 is one of the
Notch-mediated downstream genes. Moreover, both NR4A2 and Notch1 suppressed the
expression of tumor suppressors p21 and p63. These findings support that
Notch1/NR4A2 co-regulate HCC cell functions by playing oncogenic roles and
regulating the associated downstream signaling pathways. Novel Notch1/NR4A2
mediated oncogenic signaling may provide us a great opportunity for anti-HCC drug
development.
PMID- 28423576
TI - Solitary ground-glass opacity nodules of stage IA pulmonary adenocarcinoma:
combination of 18F-FDG PET/CT and high-resolution computed tomography features to
predict invasive adenocarcinoma.
AB - To investigate the performance of combined 18F-FDG Positron Emission
Tomography/Computed Tomography with high-resolution CT for differentiating
invasive adenocarcinoma from adenocarcinoma in situ (pre-invasive lesion) or
minimally invasive adenocarcinoma in stage IA lung cancer patients with solitary
ground-glass opacity nodules. This retrospective study enrolled 58 consecutive
stage IA pulmonary adenocarcinoma patients with solitary ground-glass opacity
nodules. The characteristics and measurements of the ground-glass opacity nodules
as pure ground-glass opacity nodules and mixed ground-glass opacity nodules in
the pre-invasive or minimally invasive adenocarcinoma and invasive adenocarcinoma
groups on Positron Emission Tomography/Computed Tomography and high-resolution CT
were compared and analyzed. Ground-glass opacity nodules in the pre-invasive or
minimally invasive adenocarcinoma group preferentially manifested as pure ground
glass opacity nodule (p < 0.01) compared to the invasive adenocarcinoma group.
While cystic appearance was more common in the invasive adenocarcinoma group (p <
0.05). Significant differences were found in the diameter of the ground-glass
opacity nodule itself and its solid component, and consolidation/tumor ratio
between the two groups. The sensitivity in predicting invasive adenocarcinoma was
higher with a combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46 in
mixed ground-glass opacity nodule when compared to those of SUVmax > 0.95 alone
or consolidation/tumor ratio> 0.39 alone (both p > 0.05). For a mixed ground
glass opacity nodule combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46
appears to better predict invasive adenocarcinoma in stage IA lung cancer
patients with solitary ground-glass opacity nodules.
PMID- 28423577
TI - The cyclin-like protein, SPY1, regulates the ERalpha and ERK1/2 pathways
promoting tamoxifen resistance.
AB - The Ras/Raf/MEK/ERK pathway conveys growth factor and mitogen signalling to
control the phosphorylation of a plethora of substrates regulating proliferation,
survival, and migration. The Ras signalling pathway is frequently associated with
poor prognosis and drug resistance in various cancers including those of the
blood, breast and prostate. Activation of the downstream effector ERK does not
always occur via a linear cascade of events; complicating the targeting of this
pathway therapeutically. This work describes a novel positive feedback loop where
the cell cycle regulatory factor Spy1 (RINGO; gene SPDYA) activates ERK1/2 in a
MEK-independent fashion. Spy1 was originally isolated for the ability to
stimulate Xenopus oocyte maturation via a MAPK-signalling pathway and is known to
override apoptosis triggered by the DNA damage response. We demonstrate that
mammalian Spy1-mediated ERK activation increases ligand-independent
phosphorylation and activation of estrogen receptor alpha, correlating with a
decrease in tamoxifen sensitivity. This could define a novel druggable mechanism
driving proliferation and resistance in select cancers.
PMID- 28423578
TI - Endothelial microparticles delivering microRNA-155 into T lymphocytes are
involved in the initiation of acute graft-versus-host disease following
allogeneic hematopoietic stem cell transplantation.
AB - Endothelial microparticles (EMPs) upregulation has been observed in acute graft
versus-host disease (aGVHD) after allogeneic hematopoietic stem cell
transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found
that EMPs derived from TNF-alpha-stimulated human umbilical vein endothelial
cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal
cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice
were remarkably elevated and significantly higher than the levels in plasma.
Moreover, the rising peak of miR-155 in MPs occurred significantly prior to the
peak in T lymphocytes. Additionally, we observed fluorescently-labeled miR-155 in
EMPs actively transported into recipient T lymphocytes. Inhibition of miR-155 in
EMPs by antagomir-155 did not influence the proliferation and apoptosis of T
lymphocytes, but induced defective differentiation toward Th1, Th9 and Th17 cells
and skewed differentiation toward Th2 and Treg cells. Furthermore, intravenous
injection of miR-155-deficient-EMPs into aGVHD mice significantly attenuated the
exacerbation of aGVHD manifestations and abnormal T lymphocytes differentiation
induced by high concentration EMPs. Taken together, these data provide a
mechanistic framework in which miR-155 delivered by EMPs is involved in aGVHD
pathogenesis by activating specific T lymphocytes functions. The results may
provide new therapeutic approaches for aGVHD while preserving graft-versus
leukemia (GVL) effect.
PMID- 28423579
TI - Systematic review with network meta-analysis: comparative efficacy of different
enteral immunonutrition formulas in patients underwent gastrectomy.
AB - OBJECTIVES: Optimal enteral immunonutrition (EIN) regime for gastric cancer (GC)
patients underwent gastrectomy remains uncertainty. To assess comparative
efficacy of different EIN formulas in GC patients underwent gastrectomy, we
performed network meta-analysis. RESULTS: We included 11 RCTs enrolling 840
patients. Pairwise meta-analysis indicated that EIN (RR 0.56, 95% CI 0.36-0.86;
MD -0.42, 95% CI -0.74-0.10), Arg+RNA+omega-3-FAs (RR 0.37, 95% CI 0.22-0.63; MD
0.42, 95% CI -0.75-0.07), Arg+Gln+omega-3-FAs (RR 0.22, 95% CI 0.05-0.94; MD
0.69, 95% CI -1.22-1.07) reduced ICs and LOS. Network meta-analysis confirmed the
potential of Arg+RNA+omega-3-FAs for ICs (OR 0.27, 95% Crl 0.12-0.49) and
Arg+Gln+omega-3-FAs for CIs (OR 0.22, 95% Crl 0.02-0.84) and LOS (SMD -0.63, 95%
Crl -1.07-0.13), and indicated that Arg+RNA+omega-3-FAs was superior to Arg+RNA
and Arg+Gln for ICs as well. MATERIALS AND METHODS: We performed direct and
network meta-analyses for randomized controlled trials comparing EIN formulas
with each other or standard enteral nutrition (SEN) in reducing infectious
complications (ICs), noninfectious complications (NICs) and length of hospital
stay (LOS), through January 2016. The surface under the cumulative ranking curve
(SCURA) and Grading of Recommendations Assessment, Development and Evaluation
(GRADE) were used to rank regimes and rate qualities of evidences respectively.
CONCLUSIONS: As for GC patients underwent gastrectomy, Arg+RNA+omega-3-FAs and
Arg+Gln+omega-3-FAs are the optimal regimes of reducing ICs and LOS.
PMID- 28423580
TI - Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes hypoxia-induced glioma
migration and invasion.
AB - Poor prognosis of glioblastoma multiforme is strongly associated with the ability
of tumor cells to invade the brain parenchyma, which is believed to be the major
factor responsible for glioblastoma recurrence. Therefore, identifying the
molecular mechanisms driving invasion may lead to the development of improved
therapies for glioblastoma patients. Here, we investigated the role of
procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing
collagen cross-linking, in the biology of glioblastoma invasion. PLOD2 mRNA was
significantly overexpressed in glioblastoma compared to low-grade tumors based on
the Oncomine datasets and REMBRANDT database for human gliomas. Kaplan-Meier
estimates based on the TCGA dataset demonstrated that high PLOD2 expression was
associated with poor prognosis. In vitro, hypoxia upregulated PLOD2 protein in
U87 and U251 human glioma cell lines. siRNA knockdown of endogenous HIF-1alpha or
treatment of cells with the HIF-1alpha inhibitor PX-478 largely abolished the
hypoxia-mediated PLOD2 upregulation. Knockdown of PLOD2 in glioma cell lines led
to decreases in migration and invasion under normoxia and hypoxia. In addition,
levels of phosphorylated FAK (Tyr 397), an important kinase mediating cell
adhesion, were reduced in U87-shPLOD2 and U251-shPLOD2 cells, particularly under
hypoxic conditions. Finally, orthotopic U251-shPLOD2 xenografts were
circumscribed rather than locally invasive. In conclusion, the results indicated
that PLOD2 was a gene of clinical relevance with implications in glioblastoma
invasion and treatment strategies.
PMID- 28423581
TI - DEK associates with tumor stage and outcome in HPV16 positive oropharyngeal
squamous cell carcinoma.
AB - Oropharyngeal squamous cell carcinomas (OPSCC) are common, have poor outcomes,
and comprise two biologically and clinically distinct diseases. While OPSCC that
arise from human papillomavirus infections (HPV+) have better overall survival
than their HPV- counterparts, the incidence of HPV+ OPSCC is increasing
dramatically, affecting younger individuals which are often left with life-long
co-morbidities from aggressive treatment. To identify patients which do poorly
versus those who might benefit from milder regimens, risk-stratifying biomarkers
are now needed within this population. One potential marker is the DEK
oncoprotein, whose transcriptional upregulation in most malignancies is
associated with chemotherapy resistance, advanced tumor stage, and worse
outcomes. Herein, a retrospective case study was performed on DEK protein
expression in therapy-naive surgical resections from 194 OPSCC patients. We found
that DEK was associated with advanced tumor stage, increased hazard of death, and
interleukin IL6 expression in HPV16+ disease. Surprisingly, DEK levels in HPV16-
OPSCC were not associated with advanced tumor stage or increased hazard of death.
Overall, these findings mark HPV16- OPSCC as an exceptional malignancy were DEK
expression does not correlate with outcome, and support the potential prognostic
utility of DEK to identify aggressive HPV16+ disease.
PMID- 28423582
TI - Parthenolide suppresses non-small cell lung cancer GLC-82 cells growth via B
Raf/MAPK/Erk pathway.
AB - Non-small cell lung cancer (NSCLC), one type of lung cancer, owns high rates of
morbidity and mortality. B-Raf is one of the promising oncogenic drivers of
NSCLC. Parthenolide, a natural product, is mainly extracted from the herbal plant
Tanacetum parthenium. The effect of parthenolide on NSCLC cells and its potential
as B-Raf inhibitor were studied in this study. It's shown that parthenolide
exhibited the strong cytotoxicity against NSCLC cells with IC50 ranging from 6.07
+/- 0.45 to 15.38 +/- 1.13 MUM. Parthenolide was also able to induce apoptosis,
suppress proliferation and invasion in NSCLC cells. In terms of the involved
mechanism, parthenolide suppressed GLC-82 cell response via targeting on B-Raf
and inhibiting MAPK/Erk pathway signaling. The effect of parthenolide on B-Raf
and MAPK/Erk pathway was further confirmed by RNA interference of B-Raf.
Decreased expression of c-Myc in protein and mRNA level was also discovered,
which is considered as the further downstream of the MAPK/Erk pathway. In
addition, STAT3 activity inhibition by parthenolide contributed to its effect on
GLC-82 cells, which is independent of PI3K pathway signaling and GSK3. All above
provide an insight to understand the action of parthenolide as a potential B-Raf
inhibitor in treatment of NSCLC.
PMID- 28423583
TI - The protection of meloxicam against chronic aluminium overload-induced liver
injury in rats.
AB - The present study was designed to observe the protective effect and mechanisms of
meloxicam on liver injury caused by chronic aluminium exposure in rats. The
histopathology was detected by hematoxylin-eosin staining. The levels of
prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were
detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases
2, prostaglandin E2 receptors and protein kinase A were measured by western
blotting and immunohistochemistry. Our experimental results showed that aluminium
overload significantly damaged the liver. Aluminium also significantly increased
the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine
monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and
the levels of inflammation and oxidative stress, while significantly decreased
the EP3 expression in liver. The administration of meloxicam significantly
improved the impairment of liver. The contents of prostaglandin E2 and cyclic
adenosine monophosphate were significantly decreased by administration of
meloxicam. The administration of meloxicam also significantly decreased the
expressions of cyclooxygenases-2 and protein kinase A and the levels of
inflammation and oxidative stress, while significantly increased the EP1,2,3,4
expressions in rat liver. Our results suggested that the imbalance of
cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved
in the injury of chronic aluminium-overload rat liver. The protective mechanism
of meloxicam on aluminium-overload liver injury is attributed to reconstruct the
balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.
PMID- 28423584
TI - Hepatocyte growth factor is a prognostic marker in patients with colorectal
cancer: a meta-analysis.
AB - Hepatocyte growth factor (HGF) is a crucial factor associated with development,
progression and metastasis of colorectal cancer (CRC). However, its prognostic
value remains unclear. Thus studies referring to the correlation between HGF and
CRC patients' prognosis were included to explore the role of HGF in CRC. At last
nine articles were included. The results showed that the over-expression of HGF
was associated with a poor prognosis, presented through overall survival (OS,
Hazard ratio (HR) = 2.50, 95% confidence interval (CI): 2.12-2.96) and disease
free survival (DFS, HR = 1.99, 95% CI: 1.59-2.50). Subgroup analysis indicated
that no significant difference was found between the Asian countries (OS: HR =
2.37; DFS: HR = 2.02) and the non-Asian countries (OS: HR = 3.15; DFS: HR =
1.87), between the studies that used univariate analyses (OS: HR = 2.51; DFS: HR
= 2.07) and those that used multivariate analyses (OS: HR = 2.65; DFS: HR =
1.78), and between metastatic CRC (OS: HR = 2.26; DFS: HR = 2.06) and stage I-IV
CRC (OS: HR = 3.08; DFS: HR = 0.70). Our meta-analysis has shown that the over
expression of HGF is valuable in CRC prognosis evaluation. This conclusion should
be further confirmed by large-sample cohort studies.
PMID- 28423585
TI - The rs1550117 A>G variant in DNMT3A gene promoter significantly increases non
small cell lung cancer susceptibility in a Han Chinese population.
AB - In this study, we conducted a case-control study to explore the association
between rs1550117 A>G variant of DNMT3A gene promoter and non-small cell lung
cancer (NSCLC) susceptibility in a Han Chinese population. The genotyping of
rs1550117 A>G variant was performed by polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Allele G of
rs1550117 was associated with an increased risk of NSCLC. Moreover, individuals
carrying the GG genotypes had a higher risk to develop NSCLC than the AA and GA
genotype carriers. Further stratified analysis showed that rs1550117 A>G was
significantly related to age (> 60 years), male, smoking and drinking. In vivo
detection of DNMT3A mRNA levels in NSCLC tissues and in vitro luciferase assays
consistently showed that the allele G significantly decreased DNMT3A
transcription. Additional functional analysis revealed that the increased binding
affinity of transcription repressor SP1, which was associated with allele G of
rs1550117, led to the significant decreased expression of DNMT3A. Collectively,
our results propose a suppression role of DNMT3A in NSCLC development and
emphasize the dual roles of DNMT3A in tumorigenesis.
PMID- 28423586
TI - The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of
ovarian cancer cells.
AB - PUMA is a member of the "BH3-only" branch of the BCL-2 family. Our previous study
suggests a therapeutic potential of PUMA in treating ovarian cancer, however, the
action mechanism of PUMA remains elusive. In this work, we found that in PUMA
adenovirus-infected A2780s ovarian cancer cells, exogenous PUMA was partially
accumulated in the cytosol and mainly located to the mitochondria. We further
showed that PUMA induces mitochondrial dysfunction-mediated apoptosis and ROS
generation through functional BAX in a ROS generating enzyme- and caspase
independent manner irrespective of their p53 status, and results in activation of
Nrf2/HO-1 pathway. Furthermore, PUMA induces DNA breaks in gamma-H2AX staining,
and causes activation of DNA damage-related kinases including ATM, ATR, DNA-PKcs,
Chk1 and Chk2, which are correlated with the apoptosis. PUMA also results in ROS
triggered JNK activation. Intriguingly, JNK plays a dual role in both DNA damage
response and apoptosis, and has an additional contribution to apoptosis. Taken
together, we have provided new insight into the action mechanism by which
elevated PUMA first induces ROS generation then results in DNA damage response
and JNK activation, ultimately contributing to apoptosis in ovarian cancer cells.
PMID- 28423587
TI - The correlation between programmed death-ligand 1 expression and driver gene
mutations in NSCLC.
AB - OBJECTIVES: This study aimed to evaluate the correlation between positive PD-L1
expression and driver gene mutations in NSCLC and to seek preliminary evidence in
favor of the strategy of PD-L1 inhibitors plus targeted agents. RESULTS: The
overall analyses revealed that positive PD-L1 expression had a significant
relationship with KRAS status (RR = 1.26; 95% CI, 1.06-1.50, P = 0.010), but no
correlation with clinical characteristics (gender, smoking status, histological
types), driver gene status (EGFR, ALK) and overall survival (OS): male versus
female (RR = 1.16; 95% CI, 0.95-1.42; P = 0.15), never smoking versus
former/current smoking (RR = 0.79; 95% CI, 0.56-1.11; P = 0.17), adenocarcinoma
versus non-adenocarcinoma (RR = 0.94; 95% CI, 0.63-1.41; P = 0.77), EGFR mutation
versus EGFR wild type (RR = 0.74; 95% CI, 0.52-1.06; P = 0.10), ALK positive
versus ALK negative (RR = 1.02; 95% CI, 0.75-1.38; P = 0.91), OS of positive PD
L1 expression versus that of negative PD-L1 expression (HR = 1.31, 95% CI, 0.90
1.90; P = 0.15), respectively. Noteworthily, subgroup analyses exhibited that in
Chinese cohort studies, positive PD-L1 expression was significantly correlated
with OS (HR = 1.75, 95% CI, 1.36-2.24, P < 0.0001); and in the studies using PD
L1 monoclonal antibodies (McAbs), positive PD-L1 expression was significantly
correlated with KRAS mutation (RR = 1.32, 95% CI, 1.06-1.65, P = 0.01) and EGFR
mutation (RR = 0.51, 95% CI, 0.28-0.93, P = 0.03). MATERIALS AND METHODS: After
thoroughly searching PubMed, EMBASE and Cochrane Library databases, 11 relevant
studies incorporating 3128 cases were identified. The pooled data were analyzed
via Review manager 5.3 software. CONCLUSIONS: PD-L1 inhibitors probably was a
potential promising option to manage advanced NSCLC harboring KRAS mutation.
PMID- 28423588
TI - Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated
increase in CA916798.
AB - The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung
cancer (SCLC). However, the relationship between Shp2 and resistance to
chemotherapy remains unclear. Here, we show that Shp2 plays an important role in
inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798
pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin
resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798.
Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA
interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and
CA916798 expression levels. Activation of AKT stimulated CA916798 expression and
altered the level of Shp2. A mouse xenograft model verified the results obtained
from the in vitro experiments. In addition, we collected and analyzed clinical
SCLC specimens and found that Shp2 levels correlated with CA916798 expression in
tumor tissues. Importantly, higher levels of Shp2 or CA916798 were associated
with a poorer prognosis in SCLC patients who received chemotherapy. Together, our
findings indicate that Shp2 induces cisplatin resistance in SCLC patients via the
SHP2-AKT-CA916798 pathway. Therefore, Shp2 and CA916798 may be promising
biomarkers for predicting resistance to chemotherapy and may function as targets
for enhancing treatments.
PMID- 28423589
TI - Role of microRNA-21 in radiosensitivity in non-small cell lung cancer cells by
targeting PDCD4 gene.
AB - This study aims to explore the effects of microRNA-21 (miR-21) on
radiosensitivity in non-small cell lung cancer (NSCLC) by targeting programmed
cell deanth 4 (PDCD4) and regulating PI3K/AKT/mTOR signaling pathway. Cancer
tissues and adjacent normal tissues were collected from 97 NSCLC patients who
received a standard radiotherapy regimen. TUNEL assay was applied to determine
cell apoptosis in tissues. The qRT-PCR assay was used to detect the expressions
of miR-21 expression and PDCD4 mRNA. The protein expressions of PDCD4 and
PI3K/AKT/mTOR signaling pathway-related proteins were determined by Western
blotting. Colony formation assay was used to observe the sensitivity to
radiotherapy of NSCLC cells. Flow cytometry was adopted to testify cell
apoptosis. Compared with adjacent normal tissues, miR-21 expression was
significantly increased and the mRNA and protein expressions of PDCD4 were
decreased in NSCLC tissues. Higher miR-21 expression was associated with
attenuated radiation efficacy and shorter median survival time. PDCD4 was the
target gene of miR-21. The miR-21 mimics and siRNA-PDCD4 decreased the
sensitivity to radiotherapy and cell apoptosis of A549 and H1299 cells and
activated PI3K/AKT/mTOR pathway. The sensitivity of A549 and H1299 cells was
strengthened in the miR-21 inhibitors group and the PI3K/AKT/mTOR inhibitors
group. The siRNA-PDCD4 could reverse the effects of miR-21 inhibitors on
sensitivity to radiotherapy and cell apoptosis of NSCLC cells. Our findings
provide strong evidence that miR-21 could inhibit PDCD4 expression and activate
PI3K/AKT/mTOR signaling pathway, thereby affecting the radiation sensitivity of
NSCLC cells.
PMID- 28423590
TI - Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by
downregulating Th2 and Th17 responses and upregulating the Treg response.
AB - Allergic rhinitis (AR) has long been considered to predominantly involve the
actions of Th2 cells, with relatively small contributions from Th1 cells. In
recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered
the Th1/Th2 balance paradigm more complex and expanded our understanding of the
pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to
induce allergen-specific Th2 cell activation, eosinophil and neutrophil
accumulation, and serum IgE production in asthma; all of these features may play
important roles in AR. To the best of our knowledge, only a few studies have
assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the
principal objectives of the present study were, first, to determine the status of
Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to
investigate the effects of IL-17 on such cells and the therapeutic efficacy of
anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given
intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced
AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and
neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti
IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes,
decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses,
and increased the Treg response. Anti-IL-17 Ab treatment protects against AR.
These results will improve our understanding of AR pathogenesis and may lead to
the development of novel therapeutic approaches for management of the condition.
PMID- 28423591
TI - PIK3CA mutation and colorectal cancer precision medicine.
PMID- 28423592
TI - Protective effect of hydrogen sulphide against myocardial hypertrophy in mice.
AB - Cardiac hypertrophy is a critical component of phenotype in the failing heart.
Recently, increasing evidence has demonstrated that oxidative stress plays an
important role in the pathogenesis of myocardial hypertrophy. In the present
study, we generated a mouse model of transverse aortic constriction (TAC) to
investigate whether hydrogen sulfide (H2S) has protective effects against cardiac
hypertrophy. Left ventricular structure was analyzed by two-dimensional
echocardiography. Oxidative stress was evaluated by measuring malondialdehyde,
superoxide dismutase, glutathione peroxidase and reactive oxygen specie in the
myocardium. Angiotensin II (Ang-II) was used to induce cardiomyocyte hypertrophy.
Neonatal rat cardiomyocytes pretreated with H2S donor sodium hydrosulfide prior
to Ang-II exposure were used to determine the involvement of Nrf2 and PI3K/Akt
pathway in the antioxidant effects of H2S. Our findings showed that H2S could
protect against cardiac hypertrophy by attenuating oxidative stress. The
antioxidant roles of H2S in myocardial hypertrophy probably depend on the
activation of PI3K/Akt signaling, which consequently increases Nrf2 activity and
HO-1 and GCLM expression. In summary, H2S may exert antioxidant effect on cardiac
hypertrophy via PI3K/Akt-dependent activation of Nrf2 pathway.
PMID- 28423593
TI - Anti-cancer effect of novel PAK1 inhibitor via induction of PUMA-mediated cell
death and p21-mediated cell cycle arrest.
AB - Hyper-activation of PAK1 (p21-activated kinase 1) is frequently observed in human
cancer and speculated as a target of novel anti-tumor drug. In previous, we also
showed that PAK1 is highly activated in the Smad4-deficient condition and
suppresses PUMA (p53 upregulated modulator of apoptosis) through direct binding
and phosphorylation. On the basis of this result, we have tried to find novel
PAK1-PUMA binding inhibitors. Through ELISA-based blind chemical library
screening, we isolated single compound, IPP-14 (IPP; Inhibitor of PAK1-PUMA),
which selectively blocks the PAK1-PUMA binding and also suppresses cell
proliferation via PUMA-dependent manner. Indeed, in PUMA-deficient cells, this
chemical did not show anti-proliferating effect. This chemical possessed very
strong PAK1 inhibition activity that it suppressed BAD (Bcl-2-asoociated death
promoter) phosphorylation and meta-phase arrest via Aurora kinase inactivation in
lower concentration than that of previous PAK1 kinase, FRAX486 and AG879.
Moreover, our chemical obviously induced p21/WAF1/CIP1 (Cyclin-dependent kinase
inhibitor 1A) expression by releasing from Bcl-2 (B-cell lymphoma-2) and by
inhibition of AKT-mediated p21 suppression. Considering our result, IPP-14 and
its derivatives would be possible candidates for PAK1 and p21 induction targeted
anti-cancer drug.
PMID- 28423594
TI - The hypoxia-activated prodrug evofosfamide in combination with multiple regimens
of radiotherapy.
AB - The promising treatment combination of ionizing radiation (IR) with a hypoxia
activated prodrug (HAP) is based on biological cooperation. Here we investigated
the hypoxia-activated prodrug evofosfamide in combination with different
treatment regimens of IR against lung A549- and head&neck UT-SCC-14-derived tumor
xenografts. DNA damage-related endpoints and clonogenic cell survival of A549 and
UT-SCC-14 carcinoma cells were probed under normoxia and hypoxia.Evofosfamide (TH
302) induced DNA-damage and a dose-dependent antiproliferative response in A549
cells on cellular pretreatment under hypoxia, and supra-additively reduced
clonogenic survival in combination with IR. Concomitant treatment of A549-derived
tumor xenografts with evofosfamide and fractionated irradiation induced the
strongest treatment response in comparison to the corresponding neoadjuvant and
adjuvant regimens. Adjuvant evofosfamide was more potent than concomitant and
neoadjuvant evofosfamide when combined with a single high dose of IR. Hypoxic UT
SCC-14 cells and tumor xenografts thereof were resistant to evofosfamide alone
and in combination with IR, most probably due to reduced P450 oxidoreductase
expression, which might act as major predictive determinant of sensitivity to
HAPs.In conclusion, evofosfamide with IR is a potent combined treatment modality
against hypoxic tumors. However, the efficacy and the therapeutic outcome of this
combined treatment modality is, as indicated here in preclinical tumor models,
dependent on scheduling parameters and tumor type, which is most probably related
to the status of respective HAP-activating oxidoreductases. Further biomarker
development is necessary for the launch of successful clinical trials.
PMID- 28423595
TI - dUTPase inhibition augments replication defects of 5-Fluorouracil.
AB - The antimetabolite 5-Fluorouracil (5-FU) is used in the treatment of various
forms of cancer and has a complex mode of action. Despite 6 decades in clinical
application the contribution of 5-FdUTP and dUTP [(5-F)dUTP] and 5-FUTP
misincorporation into DNA and RNA respectively, for 5-FU-induced toxicity is
still under debate.This study investigates DNA replication defects induced by 5
FU treatment and how (5-F)dUTP accumulation contributes to this effect. We reveal
that 5-FU treatment leads to extensive problems in DNA replication fork
progression, causing accumulation of cells in S-phase, DNA damage and ultimately
cell death. Interestingly, these effects can be reinforced by either depletion or
inhibition of the deoxyuridine triphosphatase (dUTPase, also known as DUT),
highlighting the importance of (5-F)dUTP accumulation for cytotoxicity.With this
study, we not only extend the current understanding of the mechanism of action of
5-FU, but also contribute to the characterization of dUTPase inhibitors. We
demonstrate that pharmacological inhibition of dUTPase is a promising approach
that may improve the efficacy of 5-FU treatment in the clinic.
PMID- 28423596
TI - Transient activation of the PI3K/Akt pathway promotes Newcastle disease virus
replication and enhances anti-apoptotic signaling responses.
AB - Viral infection activates a host's cellular phosphatidylinositol 3-kinase
(PI3K)/Akt signaling pathway, which is involved in cell differentiation, growth,
survival, and apoptosis. To elucidate molecular mechanisms in the pathogenesis of
Newcastle disease virus (NDV), we demonstrated that NDV transiently activates the
PI3K/Akt pathway in chicken cells at an early phase of infection. Its activation
was observed as early as 15 min post-infection and gradually weakened after 24 h.
Incubating cells with a PI3K inhibitor, LY294002 or wortmannin, prior to NDV
infection decreased NDV progeny yields and suppressed Akt phosphorylation at
early times post-infection. Akt activation is triggered by NDV-GM or NDV-F48E9
and is abolished by methyl beta-cyclodextrin and chlorpromazine. Treatment
following NDV-La Sota infection had no obvious effect. However, inhibiting PI3K
activation promoted apoptotic responses during an early stage of NDV infection.
The pan caspase inhibitor ZVAD-FMK mitigated the reduction in Akt phosphorylation
by inhibiting PI3K activation, which indicates the signaling pathway promotes
cell survival and, in turn, facilitates viral replication. By suppressing
premature apoptosis upon NDV infection, the PI3K/Akt pathway enhances the anti
apoptotic response.
PMID- 28423597
TI - HRD1 sensitizes breast cancer cells to Tamoxifen by promoting S100A8 degradation.
AB - Estrogen receptor alpha positive (ER+) of breast cancer could develop resistance
to antiestrogens including Tamoxifen. Our previous study showed that the E3
ubiquitin ligase HRD1 played an important role in anti-breast cancer. However,
its role in chemotherapy resistance hasn't been reported. In this study, we found
that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell
line MCF7/Tam compared to the Tamoxifen sensitive cell line MCF7. Moreover,
S100A8 is the direct target of HRD1 by proteome analysis. Our data showed that
HRD1 decreased the protein level of S100A8 through ubiquitination while HRD1 was
regulated by acetylation of histone. More importantly, HRD1 knockdown
significantly increased the cell survival of MCF7 cells to the Tamoxifen
treatment. HRD1 overexpression sensitized MCF7/Tam cells to the Tamoxifen
treatment in vitro and in vivo. In conclusion, the decrease of HRD1 expression
contributed to Tamoxifen resistance in breast cancer.
PMID- 28423598
TI - Next generation mapping reveals novel large genomic rearrangements in prostate
cancer.
AB - Complex genomic rearrangements are common molecular events driving prostate
carcinogenesis. Clinical significance, however, has yet to be fully elucidated.
Detecting the full range and subtypes of large structural variants (SVs), greater
than one kilobase in length, is challenging using clinically feasible next
generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new
technology that allows for the interrogation of megabase length DNA molecules
outside the detection range of single-base resolution NGS. In this study, we
sought to determine the feasibility of using the Irys (Bionano Genomics Inc.)
nanochannel NGM technology to generate whole genome maps of a primary prostate
tumor and matched blood from a Gleason score 7 (4 + 3), ETS-fusion negative
prostate cancer patient. With an effective mapped coverage of 35X and sequence
coverage of 60X, and an estimated 43% tumor purity, we identified 85 large
somatic structural rearrangements and 6,172 smaller somatic variants,
respectively. The vast majority of the large SVs (89%), of which 73% are
insertions, were not detectable ab initio using high-coverage short-read NGS.
However, guided manual inspection of single NGS reads and de novo assembled
scaffolds of NGM-derived candidate regions allowed for confirmation of 94% of
these large SVs, with over a third impacting genes with oncogenic potential. From
this single-patient study, the first cancer study to integrate NGS and NGM data,
we hypothesise that there exists a novel spectrum of large genomic rearrangements
in prostate cancer, that these large genomic rearrangements are likely early
events in tumorigenesis, and they have potential to enhance taxonomy.
PMID- 28423599
TI - Re-expression of miR-200c suppresses proliferation, colony formation and in vivo
tumor growth of murine claudin-low mammary tumor cells.
AB - Claudin-low breast cancer is a relatively rare breast cancer subtype. These
cancers are typically ER-/PR-/HER2- and express high levels of mesenchymal genes
as well as genes associated with inflammation, angiogenesis and stem cell
function. In addition to alterations in gene expression, it was recently
demonstrated that claudin-low breast cancers express very low levels of the miR
200 family of miRNAs. Given that each miRNA can regulate tens, hundreds or even
thousands of genes, miRNAs are being evaluated as therapeutic targets. In this
study we show that mammary tumors from MTB-IGFIR transgenic mice and cell lines
derived from these tumors represent a model of human claudin-low breast cancer
and murine claudin-low mammary tumors and cell lines express only very low levels
of all five members of the miR-200 family. Reduced miR-200 family expression
appears to be regulated via methylation as cells and tumors expressing low levels
of miR-200 family members had higher levels of CpG methylation in a putative
promoter region than tumors and cells expressing high levels of miR-200 family
members. Re-expression of miR-200c in murine claudin-low mammary tumor cells
inhibited tumor cell proliferation and colony formation in vitro and tumor growth
in vivo. With respect to tumor growth in vivo, re-expression of miR-200c was
associated with a reduction in tumor vasculature and expression of Flt1 and
Vegfc. Therefore, miR-200c is an important regulator of mesenchymal tumor cell
growth.
PMID- 28423600
TI - Systematic screening of isogenic cancer cells identifies DUSP6 as context
specific synthetic lethal target in melanoma.
AB - Next-generation sequencing has dramatically increased genome-wide profiling
options and conceptually initiates the possibility for personalized cancer
therapy. State-of-the-art sequencing studies yield large candidate gene sets
comprising dozens or hundreds of mutated genes. However, few technologies are
available for the systematic downstream evaluation of these results to identify
novel starting points of future cancer therapies.We improved and extended a site
specific recombination-based system for systematic analysis of the individual
functions of a large number of candidate genes. This was facilitated by a novel
system for the construction of isogenic constitutive and inducible gain- and loss
of-function cell lines. Additionally, we demonstrate the construction of isogenic
cell lines with combinations of the traits for advanced functional in vitro
analyses. In a proof-of-concept experiment, a library of 108 isogenic melanoma
cell lines was constructed and 8 genes were identified that significantly reduced
viability in a discovery screen and in an independent validation screen. Here, we
demonstrate the broad applicability of this recombination-based method and we
proved its potential to identify new drug targets via the identification of the
tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell
lines with BRAF V600E mutations and high DUSP6 expression.
PMID- 28423601
TI - A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity.
AB - The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many
of which are emerging as critical regulators of cell fate. However, their
functions as well as their transcriptional regulation are only partially
understood. The E2F1 transcription factor induces both proliferation and
apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here,
we provide evidence that a novel lncRNA named GASL1 is transcriptionally
regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or
endogenous E2Fs. Inhibition of GASL1 expression induced cell cycle progression,
and in particular, G1 exit. Moreover, GASL1 silencing enhanced cell
proliferation, while, conversely, its ectopic expression inhibited proliferation.
Knockdown of GASL1 also enhanced E2F1-induced apoptosis, suggesting the existence
of an E2F/GASL1 negative feedback loop. In agreement with this notion, silencing
of GASL1 led to increased levels of phosphorylated pRB and loss of Rb impaired
the effect of GASL1 silencing on G1 exit. Importantly, xenograft experiments
demonstrated that GASL1 deletion enhances tumor growth. Moreover, low levels of
GASL1 are associated with decreased survival of liver cancer patients. Taken
together, our data identify GASL1 as a novel lncRNA regulator of cell cycle
progression and cell proliferation with a potential role in cancer.
PMID- 28423602
TI - Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients
with urothelial carcinoma.
AB - Galectine-4 (gal-4), encoded by the LGALS4 gene, was recently shown to exhibit a
tumor suppressive effect in colorectal carcinoma and pancreatic adenocarcinoma,
although how the expression of this gene is regulated remains unknown. No reports
describe the significance of gal-4 in the malignant potential of urothelial
tumors. Thus, we analyzed LGALS4 methylation and gene expression and their
clinical relevance and biological function in urothelial carcinoma (UC). LGALS4
methylation was initially identified as a progression biomarker for UC patients
through genome-wide DNA methylation profiling of 16 tumor samples. Bisulfite
sequencing PCR and immunohistochemistry were performed to validate the promoter
methylation and expression of LGALS4. We used quantitative methylation-specific
PCR to determine the methylation levels of LGALS4 normalized to ACTB in the tumor
samples of 79 UC patients and compared the levels between patients with different
clinicopathological characteristics. The association with survival probability
was analyzed with the Kaplan-Meier method and Cox regression analysis. The
ectopic expression of gal-4 in cancer cell lines was used to address its
biological function in UC in vitro. The promoter hypermethylation of LGALS4
(>2.51, log10 scale) revealed a positive correlation with high levels of both
histological grade and tumor T category and with lymph node metastasis (all
P<=0.001). In addition, LGALS4 hypermethylation was an independent predictor of
inferior survival in UC patients (P<0.05). The ectopic expression studies
demonstrated that gal-4 suppressed urothelial cancer cell growth, migration, and
invasion. Thus, LGALS4 may function as a tumor suppressor gene in UC progression.
Our findings provide evidence that methylation-mediated LGALS4 gene repression
may be involved in urothelial tumor progression.
PMID- 28423603
TI - Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and
metastasis by activating the STAT3 pathway.
AB - Osteosarcoma is the most common primary bone malignancy in children and young
adults, but the role of adipose-derived mesenchymal stem cells (ADSCs) in the
rapid progression of osteosarcoma is still unclear. Here, we found that ADSCs
promoted tumour growth and invasion by increasing matrix metalloproteinase 2/9
(MMP2/9) expression in tumour cells. The persistent activation of signal
transducer and activator of transcription 3 (STAT3) has been shown to directly
promote tumour growth by mediating a wide spectrum of cellular responses, and
STAT3 activation was detected in osteosarcoma cells co-cultured with ADSCs or
treated with ADSC-conditioned medium. Furthermore, siRNA-mediated STAT3
inhibition in osteosarcoma cells decreased cell proliferation and invasion and
down-regulated MMP2/9 expression. In addition, a nude mouse model of osteosarcoma
was established by injecting luciferase-labelled MG63 cells into the tibia. As
shown in in vivo bioluminescence images, ADSCs promoted tumour cell
proliferation, invasion progression and metastasis. STAT3 inhibition attenuated
tumour growth and metastasis and prolonged the survival of these mice. After the
siRNA treatment, the MMP2, MMP9 and Ki67 levels decreased. Based on these data,
stromal ADSCs promote osteosarcoma progression by increasing STAT3 signalling
mediated MMP2/9 expression.
PMID- 28423604
TI - Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing
gastric cancer.
AB - Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all
gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more
aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor
prognosis. To improve understanding of AFPGC we reviewed a consecutive series of
82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC
among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed
with metastasis at the time of presentation, mainly liver metastasis. The serum
AFP level of patients with AFPGC was significantly associated with tumor
differentiation. Histologically, these AFPGC patients were composed of 34.55%
hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like
type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren
classification, and number of metastatic lymph nodes showed significant
differences among these four subtypes. The overall survival time was 42.02 months
and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee
on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and
surgery were prognostic factors for overall survival; however, TNM stage was the
only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare,
unique, and heterogeneous entity, and its proper identification and treatment
remain a challenge. More attention should be paid to AFPGC to improve patient
care and the dismal prognosis.
PMID- 28423605
TI - Pregnancy at early age is associated with a reduction of progesterone-responsive
cells and epithelial Wnt signaling in human breast tissue.
AB - BACKGROUND: Pregnancy at early age is the most significant modifiable factor
which consistently decreases lifetime breast cancer risk. However, the underlying
mechanisms haven't been conclusively identified. Studies in mice suggest a
reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a
downregulation of the Wnt signaling pathway as being one of the main mechanisms
for the protective effect of early pregnancy. The aim of our study was to
validate these findings in humans. METHODS: We collected benign breast tissue of
125 women who had been stratified according to age at first pregnancy and the
occurrence of subsequent breast cancer, and performed immunohistochemistry for
PR, Wnt4 and the Wnt-target Versican. RESULTS: The number of PR positive
epithelial cells was significantly lower in the group of women with early
pregnancy and no subsequent breast cancer compared to the group of nulliparous
women with subsequent invasive breast cancer (p = 0.0135). In women with early
pregnancy, expression of Versican and Wnt4 was significantly lower compared to
nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican
expression was also significant lower compared to women with late pregnancy (p <
0.0001). DISCUSSION: Our results confirm prior observations in mice and suggest a
role of downregulation of epithelial Wnt signaling in the protective effect of
early pregnancy in humans. This results in a decreased proliferation of
stem/progenitor cells; therefore, the Wnt signaling pathway may represent a
potential target for breast cancer prevention in humans.
PMID- 28423607
TI - Cancer and neurodegeneration: two sides, same coin?
PMID- 28423606
TI - Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the
dependence receptor EphA4.
AB - EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR)
by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as
conditional tumor suppressors, engaging cell death based on ligand availability;
this mechanism is bypassed by overexpression of DRs ligands in some aggressive
cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the
brain subventricular zone, an area where glioblastoma multiform (GBM) are thought
to originate. Here, we report that Ephrin-B3 is highly expressed in human
biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells.
Angiogenesis is directly correlated with GBM aggressiveness and we demonstrate
that Ephrin-B3 also supports the survival of endothelial cells in vitro and in
vivo. Lastly, silencing of Ephrin-B3 decreases tumor vascularization and growth
in a xenograft mice model. Interference with EphA4/Ephrin-B3 interaction could
then be envisaged as a relevant strategy to slow GBM growth by enhancing EphA4
induced cell death.
PMID- 28423609
TI - Glial phenotype modulators.
PMID- 28423608
TI - Anthracyclines suppress pheochromocytoma cell characteristics, including
metastasis, through inhibition of the hypoxia signaling pathway.
AB - Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine
tumors derived from adrenal or extra-adrenal chromaffin cells, respectively.
Metastases are discovered in 3-36% of patients at the time of diagnosis.
Currently, only suboptimal treatment options exist. Therefore, new therapeutic
compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we
investigated if anthracyclines were able to suppress the progression of
metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells
using in vitro and in vivo models, and demonstrated that anthracyclines,
particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the
binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia
response element (HRE) sites on DNA. This resulted in reduced transcriptional
activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate
kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate
dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which
consequently inhibited the growth of metastatic PHEO. Additionally, IDA
downregulated hypoxia signaling by interfering with the transcriptional
activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the
dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our
results indicate that anthracyclines are prospective candidates for inclusion in
metastatic PHEO/PGL therapy, especially in patients with gene mutations involved
in the hypoxia signaling pathway.
PMID- 28423610
TI - Targeting glutamate transporter-1 in neurological diseases.
PMID- 28423612
TI - Correction: Nebivolol, a beta1-adrenergic blocker, protects from peritoneal
membrane damage induced during peritoneal dialysis.
PMID- 28423611
TI - The stem cell/cancer stem cell marker ALDH1A3 regulates the expression of the
survival factor tissue transglutaminase, in mesenchymal glioma stem cells.
AB - Tissue transglutaminase (tTG), a dual-function enzyme with GTP-binding and
acyltransferase activities, has been implicated in the survival and chemotherapy
resistance of aggressive cancer cells and cancer stem cells, including glioma
stem cells (GSCs). Using a model system comprising two distinct subtypes of GSCs
referred to as proneural (PN) and mesenchymal (MES), we find that the
phenotypically aggressive and radiation therapy-resistant MES GSCs exclusively
express tTG relative to PN GSCs. As such, the self-renewal, proliferation, and
survival of these cells was sensitive to treatment with tTG inhibitors, with a
benefit being observed when combined with the standard of care for high grade
gliomas (i.e. radiation or temozolomide). Efforts to understand the molecular
drivers of tTG expression in MES GSCs revealed an unexpected link between tTG and
a common marker for stem cells and cancer stem cells, Aldehyde dehydrogenase 1A3
(ALDH1A3). ALDH1A3, as well as other members of the ALDH1 subfamily, can function
in cells as a retinaldehyde dehydrogenase to generate retinoic acid (RA) from
retinal. We show that the enzymatic activity of ALDH1A3 and its product, RA, are
necessary for the observed expression of tTG in MES GSCs. Additionally, the
ectopic expression of ALDH1A3 in PN GSCs is sufficient to induce the expression
of tTG in these cells, further demonstrating a causal link between ALDH1A3 and
tTG. Together, these findings ascribe a novel function for ALDH1A3 in an
aggressive GSC phenotype via the up-regulation of tTG, and suggest the potential
for a similar role by ALDH1 family members across cancer types.
PMID- 28423613
TI - Secreted GRP78 activates EGFR-SRC-STAT3 signaling and confers the resistance to
sorafeinib in HCC cells.
AB - Acquired resistance is a common phenomenon for HCC patients who undergone
sorafenib treatment, however the mechanism by which acquired resistance develops
remains elusive. In this study, we found that GRP78 could be detected in the
serum samples of HCC patients and the conditional medium of multiple HCC cell
lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed
that secreted GRP78 facilitated the proliferation and inhibited the apoptosis
induced by sorafenib both in HCC cell lines and in tumor xenografts. We further
found that secreted GRP78 could interact physically with EGFR, therefore
activates EGFR signaling pathway. knockdown of EGFR decreased secreted GRP78
induced phosphorylation of SRC and STAT3. By contrast, overexpression of EGFR
further enhanced the phosphorylation of SRC and STAT3 induced by secreted GRP78,
suggesting the critical role of EGFR in secreted GRP78 conferred resistance to
sorafeinib. Moreover, inhibition of SRC by PP2 antagonized the resistance to
sorafenib and inhibited the activation of STAT3 conferred by secreted GRP78.
Taken together, our results showed that secreted GRP78 could interact with EGFR,
activate EGFR-SRC-STAT3 signaling, conferring the resistance to sorafenib.
PMID- 28423614
TI - Marriage is a dependent risk factor for mortality of colon adenocarcinoma without
a time-varying effect.
AB - BACKGROUND: It has been well recognized that the effects of many prognostic
factors could change during long-term follow-up. Although marriage has been
proven to be a significant prognostic factor for the survival of colon cancer,
whether the effect of marriage is constant with time remain unknown. This study
analyzed the impact of marital status on the mortality of colon cancer patients
with an extended Cox model that allowed for time-varying effects. METHODS: We
identified 71,955 patients who underwent colectomy between 2004 and 2009 to treat
colon adenocarcinoma from the Surveilance, Epidemiology and End Results Database.
The multivariate extended Cox model was used to evaluate the effect of marital
status on all-cause mortality, while the Fine-Gray competing risks model was used
for colon cancer-specific mortality, with death from other causes as the
competing risk. RESULTS: The unmarried patients carried a 1.37-fold increased
risk of all-cause mortality compared with the married patients (95%CI: 1.33-1.40;
p<0.001), and the hazard ratio remained constant over time. Being unmarried was
at a higher risk of death from colon adenocarcinoma as well as death from other
causes. Four variables including tumor site, tumor grade, sex and TNM stage were
proved to have time-varying effects on survival. CONCLUSIONS: Marriage is a
dependent prognosis factor for survival of surgically treated colon
adenocarcinoma patients. Psychological interventions are suggested to improve
receipt of treatment among unmarried patients, as their poor survival may be due
to the inefficient treatment.
PMID- 28423615
TI - EXOC3L2 rs597668 variant contributes to Alzheimer's disease susceptibility in
Asian population.
AB - Recent genome-wide association studies have established the association between
EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population.
However, recent studies reported inconsistent results in Asian population. Here,
we performed a systematic review and meta-analysis to evaluate the impact of
rs597668 on AD risk in Asian population using a total of 8686 samples including
2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154
controls in European population to evaluate the potential heterogeneity between
East Asian and European populations. In East Asian population, we identified no
potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we
identified positive association between rs597668 and AD risk with P=0.023,
OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled
Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis
indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In
summary, all these findings indicate that rs597668 C allele is a risk factor for
AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C
allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian
population.
PMID- 28423616
TI - Suppression of microRNA-16 protects against acute myocardial infarction by
reversing beta2-adrenergic receptor down-regulation in rats.
AB - microRNA-16 (miR-16) has been shown to be up-regulated in ischemic heart. Beta2
adrenoreceptor (beta2-AR) exerts cardioprotective property in ischemic injury.
This study aims to determine the effect of miR-16 in cardiac injury in rats and
the possible involvement of beta2-AR in this process. Acute myocardial infarction
(AMI) model in rats was induced by ligation of left coronary artery. Neonatal rat
ventricular cells (NRVCs) were cultured in vitro tests. The cardiomyocyte model
of oxidative injury was mimicked by hydrogen peroxide. The expression of miR-16
was obviously up-regulated and beta2-AR was remarkably down-regulated in both AMI
rats and NRVCs under oxidative stress. miR-16 over-expression in NRVCs reduced
cell viability and increased apoptosis. Conversely, inhibition of endogenous miR
16 with its specific inhibitor reversed these changes. Over-expression of miR-16
using an miR-16 lentivirus in AMI rats markedly increased cardiac infarct area,
lactate dehydrogenase and creatine kinase activity, and exacerbated cardiac
dysfunction. Lentivirus-mediated knockdown of miR-16 alleviated acute cardiac
injury. Moreover, miR-16 over-expression significantly suppressed beta2-AR
protein expression in both cultured NRVCs and AMI rats, while inhibition of miR
16 displayed opposite effect on beta2-AR protein expression. Luciferase assay
confirmed that miR-16 could directly target the 3'untranslated region of beta2-AR
mRNA. miR-16 is detrimental to the infarct heart and suppression of miR-16
protects rat hearts from ischemic injury via up-regulating of beta2-AR by binding
to the 3'untranslated region of beta2-AR gene. This study indicates that
targeting miR-16/beta2-AR axis may be a promising strategy for ischemic heart
disease.
PMID- 28423617
TI - The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates
pancreatic cancer.
AB - AIM: To determine the regulation and function of the neural precursor cell
expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to
determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT
signaling. METHODS: We investigated the expression of NEDD4 and the tumor
suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line
and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether
RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and
migration. We subsequently determined the crosstalk between NEDD4 expression and
the PTEN/PI3K/AKT signaling pathway. Finally, we determined the mechanism behind
differential NEDD4 protein expression in pancreatic cancer. RESULTS: The
expression of NEDD4 was heterogeneous in PDAC cells, but was significantly higher
compared to normal pancreatic ductal epithelial cells. Analogically, PTEN was
decreased in the PDAC cells. A combination of MTT assay, wound healing migration
assay, and transwell invasion assays confirmed that depletion of NEDD4 decreased
the proliferation and migration ability of PDAC cells. Western blot and
immunofluorescence results revealed that NEDD4 could affect PTEN/PI3K/AKT
signaling pathway in PDAC cells. Polysomal profiling revealed that higher NEDD4
protein expression in PDAC cells was due to undefined mechanism involving
translational activation. CONCLUSIONS: Our results reveal a novel mechanism of
upregulation of NEDD4 expression in PDAC. Our findings indicate that NEDD4
potentially plays a critical role in activating the PI3K/AKT signaling pathway by
negatively regulating PTEN levels in PDAC cells, which promotes pancreatic cancer
cell proliferation and metastasis. Therefore, NEDD4 may be a potential
therapeutic target in PDAC.
PMID- 28423618
TI - miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma.
AB - Increasing evidence suggests that microRNAs play key roles in lung cancer. Our
previous study demonstrated that microRNA 363-3p (miR-363-3p) is downregulated in
lung cancer tissues. In this study, we demonstrated that overexpression of miR
363-3p inhibits the proliferation and colony formation of A549 and H441 cells,
while silencing of miR-363-3p has the converse effects. The anti-oncogenic
function of miR-363-3p was verified in a mouse tumor xenograft model.
Furthermore, cell cycle analysis showed miR-363-3p can induce S phase arrest by
downregulating Cyclin-D1 and upregulating Cyclin-dependent kinase-2 in lung
adenocarcinoma cells. Additionally, miR-363-3p enhances cell apoptosis, whereas
miR-363-3p inhibitor prevents apoptosis and leads to downregulation of Bax and
Bak expression. The anti-proliferative function of miR-363-3p toward lung cancer
cells may be explained by its ability to inhibit the activation of the mTOR and
ERK signaling pathways. Using target prediction software and luciferase reporter
assays, we identified PCNA as a specific target of miR-363-3p. miR-363-3p can
decreased the accumulation of endogenous PCNA in lung adenocarcinoma cells.
Moreover, exogenous expression of PCNA relieve the inhibition of miR-363-3p on
cell proliferation, colony formation and mTOR and ERK signaling pathways. Taken
together, our data indicate that miR-363-3p suppresses tumor growth by targeting
PCNA in lung adenocarcinoma.
PMID- 28423619
TI - CDCA2 promotes lung adenocarcinoma cell proliferation and predicts poor survival
in lung adenocarcinoma patients.
AB - Cell division cycle associated 2(CDCA2) is overexpressed in neuroblastoma and
oral squamous cell carcinoma, and its overexpression positively correlates to
tumor progression. However, the biological and clinical significance of CDCA2 in
lung adenocarcinoma(LAC) has never been investigated. We determined the
expression profile and clinical significance of CDCA2 using The Cancer Genome
Atlas(TCGA) and tissue microarray(TMA). Furthermore, we explored the biological
function of CDCA2 both in vitro and in vivo. A great upregulation of CDCA2 was
observed in LAC tissues compared with adjacent normal tissues. Importantly, Cox
regression analysis indicated that high level of CDCA2 was an independent risk
factor for overall survival(OS) in LAC patients (TCGA: HR = 1.720, p = 0.004;
TMA: HR = 1.971, p = 0.023). Inhibition of CDCA2 suppressed the proliferation of
LAC cells via G1 phase arrest by downregulating cyclin E1(CCNE1), while
overexpression of CDCA2 promoted LAC cells proliferation by upregulating CCNE1.
Moreover, the oncogenic activity of CDCA2 was also confirmed in vivo. In
conclusion, CDCA2 promotes proliferation of LAC cells and predicts poor prognosis
in LAC patients. CDCA2 might play a significant role in LAC progression.
PMID- 28423620
TI - Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a
possible role for exosomal disposal of tumor suppressor miRNAs.
AB - Exosomes have emerged as important mediators of diverse biological functions
including tumor suppression, tumor progression, invasion, immune escape and cell
to-cell communication, through the release of molecules such as mRNAs, miRNAs,
and proteins. Here, we identified differentially expressed exosomal miRNAs
between normal epithelial ovarian cell line and both resistant and sensitive
ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from
SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is
associated with better survival in patients with ovarian serous
cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony
formation, invasion, and migration and triggered G0/G1 cell cycle arrest and
apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth
in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly
targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein
levels. Following this inhibition, the expression of proteins downstream of SRC,
such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest
that OC cells secrete the tumor-suppressive miR-940 into the extracellular
environment via exosomes, to maintain their invasiveness and tumorigenic
phenotype.
PMID- 28423621
TI - Epstein-Barr virus encoded microRNA BART7 regulates radiation sensitivity of
nasopharyngeal carcinoma.
AB - Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very
sensitive to radiotherapy. To date, the underlying mechanism remains poorly
understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7
(ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by
targeting GFPT1/TGFbeta1 signaling. GFPT1 is the the key rate-limiting enzyme of
the hexosamine signaling pathway and governs TGFbeta1 production. TGFbeta1, a
pleotropic cytokine with the potency to trigger self-renewal and damage-repair
machinery in somatic cells. TGFbeta1 can protect zebrafish embryo from the lethal
effects of radiation treatment. In silico analysis showed that ebv-miR-BART7
could target GFPT1 transcript. Correlation analysis on primary NPC tissues
suggested that ebv-miR-BART7 and GFPT1 have negative expression correlation.
Expression of GFPT1 and TGFbeta1 were inducible by radiation in NPC cell with ebv
miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited
TGFbeta1 which subsequently increased the responsiveness of NPC to radiation
treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls
TGFbeta1 production by targeting GFPT1. Detection of ebv-miR-BART7 may provide
useful indicator for monitoring NPC progression and predict therapeutic outcomes.
PMID- 28423622
TI - HnRNPK/miR-223/FBXW7 feedback cascade promotes pancreatic cancer cell growth and
invasion.
AB - Several studies have identified miR-223 critically involved in various types of
cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action
and regulatory mechanisms in PDAC remains largely unclear. In this study, we
found that the expression levels of miR-223 were increased in clinical samples
with PDAC (81.6%). The upregulation of miR-223 increases the proliferation,
migration, and invasive abilities of PDAC cells in vitro and in vivo.
Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7
reverted miR-223- induced drastic proliferation in PDAC cells. Interestingly, miR
223 promoter was found to form a coprecipitable complex with hnRNPK, and siRNA
knockdown of hnRNPK in PDAC cells reduced the levels of miR-223. These results
show that hnRNPK is a cellular protein that binds and affects the accumulation of
miR-223 in PDAC. Furthermore, FBXW7 interacts with hnRNPK and promotes its
degradation, which requires phosphorylation of hnRNPK at threonine 1695 by GSK3.
Consistently, we observed an inverse expression pattern between FBXW7 and miR
223, whereas a positive expression pattern between miR-223 and hnRNPK was found
in human PDAC tissues. These data unveiled an important new miR-223/FBXW7/HnRNPK
feedback cascade in human PDAC.
PMID- 28423623
TI - Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell
mediated killing through matrix-metalloproteinases secretion.
AB - Cancer-associated fibroblasts (CAFs) play a central role in the complex process
of tumor-stroma interaction and promote tumor growth. Emerging evidences also
suggest that these fibroblasts are involved in the alteration of the anti-tumor
immune response by impacting several immune cell populations, especially through
their secretion of pro-inflammatory and immunosuppressive factors in the tumor
microenvironment. However, the underlying immuno-modulating mechanisms triggered
by these fibroblasts are still only partially defined. In this study, we provide
evidence that melanoma-associated fibroblasts decrease the susceptibility of
melanoma tumor cells to NK-mediated lysis through the secretion of active matrix
metalloproteinases. This secretion reduces the expression of the two NKG2D
ligands, MICA/B, at the surface of tumor cells and consequently decreases the
NKG2D-dependent cytotoxic activity of NK cells against melanoma tumor cells.
Together, our data demonstrate that the modification of tumor cell susceptibility
to killer cells is an important determinant of the anti-tumor immune response
alteration triggered by CAFs.
PMID- 28423624
TI - Assessment of female breast dose for thoracic cone-beam CT using MOSFET
dosimeters.
AB - OBJECTIVE: To assess the breast dose during a routine thoracic cone-beam CT
(CBCT) check with the efforts to explore the possible dose reduction strategy.
MATERIALS AND METHODS: Metal oxide semiconductor field-effect transistor (MOSFET)
dosimeters were used to measure breast surface doses during a thorax kV CBCT scan
in an anthropomorphic phantom. Breast doses for different scanning protocols and
breast sizes were compared. Dose reduction was attempted by using partial arc
CBCT scan with bowtie filter. The impact of this dose reduction strategy on image
registration accuracy was investigated. RESULTS: The average breast surface doses
were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with
filtration, respectively. This indicates a dose reduction of 41.8% by use of
bowtie filter. It was found 220 degrees partial arc scanning significantly
reduced the dose to contralateral breast (44.4% lower than ipsilateral breast),
while the image registration accuracy was not compromised. CONCLUSIONS: Breast
dose reduction can be achieved by using ipsilateral 220 degrees partial arc scan
with bowtie filter. This strategy also provides sufficient image quality for
thorax image registration in daily patient positioning verification.
PMID- 28423625
TI - Inhibition activity of a disulfide-stabilized diabody against basic fibroblast
growth factor in lung cancer.
AB - The over-expression of basic fibroblast growth factor (bFGF) plays a crucial role
in the development, invasion and metastasis of lung cancer. Therefore,
neutralizing antibodies against bFGF may inhibit the growth of lung cancer. In
this study, a Disulfide-stabilized diabody (ds-Diabody) against bFGF was
constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the
position of VH44 and VL100 in the scFv. The ds-Diabody was constructed and
expressed in Pichia pastoris. We found that the ds-Diabody against bFGF could
efficiently suppress the proliferation, migration and invasion of human lung
cancer A549 cells in vitro. Moreover, in A549 cells, the ds-Diabody against bFGF
could inhibit bFGF-induced activation of downstream signaling regulators, such as
phospho-Akt and phospho-MAPK. In the nude mouse xenograft model of lung cancer,
the ds-Diabody against bFGF could significantly inhibit tumor growth and decrease
the densities of micro-vessels and lymphatic vessels in tumor tissue. Our data
indicate that the ds-Diabody against bFGF could effectively suppress the lung
cancer growth through blockade of bFGF signaling pathway and inhibition of tumor
angiogenesis, which may make it a potential therapeutic candidate antibody drug
for human lung cancer therapy.
PMID- 28423627
TI - Platelet distribution width correlates with prognosis of gastric cancer.
AB - BACKGROUND: Activated platelets promote tumor cell growth, aberrant angiogenesis,
and invasion. However, the value of platelet indices for predicting survival in
gastric cancer remains unknown. The goal of this study was to investigate the
predictive significance of platelet indices in gastric cancer. RESULT: Reduced
platelet distribution width (PDW) was significantly correlated with age,
carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases
stage. Moreover, decreased PDW correlated with a shorter overall survival in
gastric cancer. Multivariate analysis identified PDW as an independent prognostic
factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319
0.761, p = 0.001). METHOD: A total of 294 patients with gastric cancer were
retrospectively analyzed between January 2009 and December 2009. The association
between platelet indices and overall survival were evaluated. The prognostic
analysis was carried out with Cox regression model. CONCLUSION: PDW is easily
available with routine blood counts. Our data revealed that reduced PDW is
unfavorable prognostic factor in gastric cancer. Further studies are warranted.
PMID- 28423626
TI - Prognostic value of loss of heterozygosity and sub-cellular localization of SMAD4
varies with tumor stage in colorectal cancer.
AB - BACKGROUND: Although loss of heterozygosity (LOH) at chromosome location 18q21
and decreased expression of SMAD4 in invasive colorectal cancers (CRCs) correlate
with poor patient survival, the prognostic value of LOH at 18q21 and sub-cellular
localization of SMAD4 have not been evaluated in relation to tumor stage.
METHODS: Genomic DNA samples from 209 formalin-fixed, paraffin-embedded sporadic
CRC tissues and their matching controls were analyzed for 18q21 LOH, and
corresponding tissue sections were evaluated by immunohistochemistry for
expression of SMAD4 and assessed for its sub-cellular localization (nuclear vs.
cytoplasmic). In addition, 53 frozen CRCs and their matching control tissues were
analyzed for their mutational status and mRNA expression of SMAD4. The phenotypic
expression pattern and LOH status were evaluated for correlation with patient
survival by the use of Kaplan-Meier and Cox regression models. RESULTS: LOH of
18q21 was detected in 61% of the informative cases. In 8% of the cases, missense
point mutations were detected in Smad4. In CRCs, relative to controls, there was
increased SMAD4 staining in the cytoplasm (74%) and decreased staining in the
nuclei (37%). LOH of 18q21 and high cytoplasmic localization of SMAD4 were
associated with shortened overall survival of Stage II patients, whereas low
nuclear expression of SMAD4 was associated with worse survival, but only for
patients with Stage III CRCs. CONCLUSIONS: LOH of 18q21 and high cytoplasmic
localization of SMAD4 in Stage II CRCs and low nuclear SMAD4 in Stage III CRCs
are predictors of shortened patient survival.
PMID- 28423628
TI - Benzyl isothiocyanate induces reactive oxygen species-initiated autophagy and
apoptosis in human prostate cancer cells.
AB - Benzyl isothiocyanate (BITC) in cruciferous plants, which are part of the human
diet, has been shown to induce apoptosis in various types of cancer. In this
study, we show that BITC effectively suppresses the growth of cultured human
prostate cancer cells (CRW-22Rv1 and PC3) by causing mitochondrial membrane
potential loss, caspase 3/7 activation and DNA fragmentation. Furthermore, BITC
induces ROS generation in these cells. The induction of apoptosis by BITC was
significantly attenuated in the presence of N-acetylcysteine (NAC) and catalase
(CAT), well-studied ROS scavengers. The induction of autophagy in BITC-treated
cells were also diminished by the application of NAC or CAT. In addition, BITC
induced apoptosis and autophagy were both enhanced by the pretreatment of
catalase inhibitor, 3-Amino-1,2,4-triazole (3-AT). Pretreatment with specific
inhibitors of autophagy (3-methyladenine or bafilomycin A1) or apoptosis (Z-VAD
FMK) reduced BITC-induced autophagy and apoptosis, respectively, but did not
abolish BITC-induced ROS generation. In conclusion, the present study provides
evidences that BITC caused prostate cancer cell death was dependent on the ROS
status, and clarified the mechanism underlying BITC-induced cell death, which
involves the induction of ROS production, autophagy and apoptosis, and the
relationship between these three important processes.
PMID- 28423629
TI - Polymorphisms in human telomerase reverse transcriptase (hTERT) gene, gene- gene
and gene-smoking interaction with susceptibility to gastric cancer in Chinese Han
population.
AB - AIMS: To investigate the association of telomerase reverse transcriptase (TERT)
gene polymorphisms and additional gene-gene and gene- environment interaction
with gastric cancer (GC) risk. RESULTS: GC risk was significantly higher in
carriers of G allele of rs2736100 than those with TT genotype (TG+ GG versus TT),
adjusted OR (95%CI) =1.68 (1.26-2.17), and higher in carriers of G allele of
rs2853669 than those with AA genotype (AG+ GG versus AA), adjusted OR (95%CI) =
1.72 (1.19-2.33). We also found that interaction between rs2736100 and smoking
was associated with higher GC risk. Smokers with TG or GG of rs2736100 genotype
have elevated GC risk, compared to never- smokers with TT of rs2736100 genotype,
OR (95%CI) = 3.12 (1.82 -4.61). Pairwise linkage equilibrium (LD) analysis
between SNPs was measured and the D' value between rs2736100 and rs2736109 was
more than 0.8. A haplotype containing the rs2736100- G and rs2736109- A alleles
was associated with a statistically increased GC risk (OR= 2.66, 95%CI= 1.28 -
4.12, p<0.0001). MATERIALS AND METHODS: A total of 1088 participants (686 males,
402 females) were selected, including 360 GC patients and 728 normal
participants. Logistic regression was performed to investigate association
between single nucleotide polymorphisms (SNPs) within TERT gene and GC
susceptibility. Generalized multifactor dimensionality reduction (GMDR) model was
used to screen gene- gene and gene- environment interaction combinations.
CONCLUSIONS: We found that G allele of rs2736100 and G allele of rs2853669 in
TERT gene, interaction between rs2736100 and smoking, and haplotype containing
the rs2736100- G and rs2736109- A alleles were all associated with increased GC
risk.
PMID- 28423631
TI - Why isn't the angiotensin type 1 receptor a target in cancer?
PMID- 28423630
TI - Insufficient hypothalamic angiotensin-converting enzyme 2 is associated with
hypertension in SHR rats.
AB - Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin-angiotensin
system (RAS), which is implicated in the pathogenesis of hypertension and other
cardiovascular diseases. In this study we investigated the expression of ACE2 in
the hypothalamus and pituitary tissues and its relationship to hypertension by
comparing them in male WKY and SHR rats. We observed that the plasma levels of
corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and
aldosterone (ALD) were all lower in SHR than WKY rats (P<0.05), whereas plasma
angiotensin II (AngII) levels were higher in SHR rats (P<0.05). Levels of ACE
mRNA and protein were higher in the hypothalamus of SHR than WKY rats (P<0.05).
By contrast, hypothalamic expression of ACE2 protein was lower in SHR rats
(P<0.05), despite comparable mRNA levels in SHR and WKY rats. There were no
differences in the expression levels of ACE, ACE2, AT1 or Mas mRNA in the
pituitaries of SHR and WKY rats (P>0.05). These results suggest that
insufficiency of hypothalamic ACE2 is associated with hypertension in SHR rats.
PMID- 28423632
TI - The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and
CE(A)F chemotherapy response to breast cancer and clinical outcomes.
AB - The PI3K/PTEN/AKT pathway play a critical role in balancing cell growth and
death. Epidemiologic studies suggested that mutations of the PI3K/PTEN/AKT
pathway genes are associated with cancer risk, yet no data are available for PTEN
rs701848, PIK3CA rs2699887, and AKT1 rs2494752 polymorphism and breast cancer(BC)
risk. A case-control study was performed in 920 BC patients and 908 healthy
controls using the TaqMan assay method. Overall, individuals with PTEN rs701848
TC, CC and TC/CC genotypes showed significant increased BC risk (P=0.043,
P=0.002, P=0.008, respectively), and the C allele carriers had a 1.224-fold
significantly increased risk of developing BC (P= 0.003). Moreover, a higher
frequency of AKT rs2494752 AG genotype was observed among cases (P=0.045).
Individuals harboring rs2494752 AG/AA genotype had a vital increased
susceptibility to BC in the dominant model (P=0.039). More importantly, AKT1
rs2494752 GG genotype showed significantly rates of response to NCT chemotherapy
(P=0.048). Furthermore, AKT1 rs2494752 AG genotype carriers showed significantly
shorter DFS time, and GG genotype as the independent prognostic factor (DFS:
adjusted HR=1.523, 95% CI=1.012-2.293, P=0.044; OS: adjusted HR=2.321, 95%
CI=1.281-4.204, P=0.005). Moreover, MDR analysis consistently revealed that the
combination of 3 selected SNPs and 7 known risk factors represented the best
model to predicting BC prognosis. The luciferase assay showed that the G allele
of rs2494752 significantly increased AKT1 promoter activity. These results
suggest that PTEN rs701848 and AKT1 rs2494752 polymorphisms might be a candidate
pharmacogenomic factor to assess the susceptibility of BC and response and
prognosis prediction for interindividualized CE(A)F chemotherapy in BC patients.
PMID- 28423633
TI - Novel lincRNA SLINKY is a prognostic biomarker in kidney cancer.
AB - Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior,
and prognostic biomarkers are needed to stratify patients for appropriate
management. We sought to determine whether long intergenic non-coding RNAs
(lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were
identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data
on 466 ccRCC cases (randomized into discovery and validation sets) annotated for
~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival
predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and
validated in an independent University of Tokyo cohort (P=0.004). In
multivariable analysis, SLINKY expression predicted overall survival independent
of tumor stage and grade [TCGA HR=3.5 (CI, 2.2-5.7), P < 0.001; Tokyo HR=8.4 (CI,
1.8-40.2), P = 0.007], and by decision tree, ROC and decision curve analysis,
added independent prognostic value. In ccRCC cell lines, SLINKY knockdown reduced
cancer cell proliferation (with cell-cycle G1 arrest) and induced transcriptome
changes enriched for cell proliferation and survival processes. Notably, the
genes affected by SLINKY knockdown in cell lines were themselves prognostic and
correlated with SLINKY expression in the ccRCC patient samples. From a screen for
binding partners, we identified direct binding of SLINKY to Heterogeneous Nuclear
Ribonucleoprotein K (HNRNPK), whose knockdown recapitulated SLINKY knockdown
phenotypes. Thus, SLINKY is a robust prognostic biomarker in ccRCC, where it
functions possibly together with HNRNPK in cancer cell proliferation.
PMID- 28423634
TI - Early assessment of tumor response to photodynamic therapy using combined diffuse
optical and diffuse correlation spectroscopy to predict treatment outcome.
AB - Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that
can be light-activated to eradicate tumors via direct cytotoxicity, damage to
tumor vasculature and stimulating the body's immune system. Treatment outcome may
vary between individuals even under the same regime; therefore a non-invasive
tumor response monitoring system will be useful for personalization of the
treatment protocol. We present the combined use of diffuse optical spectroscopy
(DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of
tumor response. The relative tissue oxygen saturation (rStO2) and relative blood
flow (rBF) in tumors were measured using DOS and DCS respectively before and
after PDT with reference to baseline values in a mouse model. In complete
responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3
h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these
parameters to baseline values was observed around 2 weeks after PDT. In partial
responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the
rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast,
the rStO2 and rBF readings in control tumors showed fluctuations above the
baseline values within the first 48 h. Therefore tumor response can be predicted
at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post
PDT corresponded to long-term tumor control. Diffuse optical measurements can
thus facilitate early assessment of tumor response. This approach can enable
physicians to personalize PDT treatment regimens for best outcomes.
PMID- 28423636
TI - Traumatic brain injury and hyperglycemia.
PMID- 28423635
TI - Quantification of HER2 and estrogen receptor heterogeneity in breast cancer by
single-molecule RNA fluorescence in situ hybridization.
AB - Intra-tumor heterogeneity is a pervasive property of human cancers that poses a
major clinical challenge. Here, we describe the characterization, at the
transcriptional level, of the intra-tumor topography of two prominent breast
cancer biomarkers and drug targets, epidermal growth factor receptor 2 (HER2) and
estrogen receptor 1 (ER) in 49 archival breast cancer samples. We developed a
protocol for single-molecule RNA FISH in formalin-fixed, paraffin-embedded tissue
sections (FFPE-smFISH), which enabled us to simultaneously detect and perform
absolute quantification of HER2 and ER mature transcripts in single cells and
multiple tumor regions. We benchmarked our method with standard diagnostic
techniques, demonstrating that FFPE-smFISH is able to correctly classify breast
cancers into well-established molecular subgroups. By counting transcripts in
thousands of single cells, we identified different expression modes and levels of
inter-cellular variability. In samples expressing both HER2 and ER, many cells co
expressed both genes, although expression levels were typically uncorrelated.
Finally, we applied diversity metrics from the field of ecology to assess the
intra-tumor topography of HER2 and ER gene expression, revealing that the spatial
distribution of these key biomarkers can vary substantially even among breast
cancers of the same subtype. Our results demonstrate that FFPE-smFISH is a
reliable diagnostic assay and a powerful method for quantification of intra-tumor
transcriptional heterogeneity of selected biomarkers in clinical samples.
PMID- 28423637
TI - Apigenin inhibits renal cell carcinoma cell proliferation.
AB - Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor
activity in several cancer types. The present study evaluated the effects and
mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found
that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose
and time-dependent manner. A comet assay suggested that apigenin caused DNA
damage in ACHN cells, especially at higher doses, and induced G2/M phase cell
cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)
mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53
dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell
xenograft mouse model. Apigenin treatment reduced tumor growth and volume in
vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors
derived from apigenin-treated mice. These findings suggest that apigenin exposure
induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis,
which collectively suppress ACHN RCC cell proliferation in vitro and in vivo.
Given its antitumor effects and low in vivo toxicity, apigenin is a highly
promising agent for treatment of RCC.
PMID- 28423638
TI - HER inhibitor promotes BRAF/MEK inhibitor-induced redifferentiation in papillary
thyroid cancer harboring BRAFV600E.
AB - Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with
radioiodine represents a good choice for radioiodine-refractory differentiated
thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound
caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance
mechanism, and combination with HER inhibitor to prevent MAPK rebound may
sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To
evaluate if inhibiting both BRAF/MEK and HER can produce stronger
redifferetiation effect, we tested the effects of BRAF/MEK inhibitor
dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on
the expression and function of iodine- and glucose-handling genes in BRAFV600E
positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement
as control. Herein, we showed that lapatinib prevented MAPK rebound and
sensitized BRAFV600E-positive papillary thyroid cancer cells to BRAF/MEK
inhibitors. Dabrafenib/selumetinib alone increased iodine-uptake and toxicity and
suppressed glucose-metablism in BRAFV600E-positive papillary thyroid cancer
cells. When lapatinib was added, more significant effects on iodine- and glucose
handling gene expression, cell membrane location of sodium/iodine symporter as
well as radioiodine uptake and toxicity were observed. Thus, combined therapy
using HER inhibitor and BRAF/MEK inhibitor presented more significant
redifferentiation effect on papillary thyroid cancer cells harboring BRAFV600E
than BRAF/MEK inhibitor alone. In vivo and clinical studies assessing such
combined targeted redifferentiation strategy were warranted.
PMID- 28423639
TI - M2 microglia promotes neurogenesis and oligodendrogenesis from neural
stem/progenitor cells via the PPARgamma signaling pathway.
AB - Neural stem/progenitor cells (NSPCs) are an important source of cells for cell
replacement therapy after nerve injury. How to induce NSPCs differentiation
towards neurons and oligodendrocytes is a challenging issue in neuroscience
research. In the present study, we polarized microglia into M1 and M2 phenotype,
used their supernatants to induce NSPCs differentiation, and investigated the
effects of different microglia phenotypes on NSPCs differentiation and their
mechanisms. We discovered that, after exposure to M1 phenotype supernatant, NSPCs
differentiated into fewer Tuj-1+ and Olig2+ cells, but more GFAP+ cells.
Meanwhile, a significantly increased number of Tuj-1+ and Olig2+ cells and
smaller number of GFAP+ cells were generated by M2 microglia supernatant-induced
NSPCs differentiation. We also observed that 15d-PGJ2, an endogenous ligand of
PPARgamma, was elevated in M2 phenotype supernatant and could activate PPARgamma
expression in NSPCs, whereas use of the PPARgamma inhibitor GW9662, could reduce
the percentage of differentiated neurons and oligodendrocytes. Our study results
confirm that M2 microglia supernatant can activate the PPARgamma signaling
pathway and promote neurogenesis and oligodendrogenesis from NSPCs
differentiation. The present study provides a further theoretical basis for
induction of NSPCs oriented differentiation.
PMID- 28423641
TI - The autophagy process.
PMID- 28423640
TI - The rostromedial tegmental nucleus and alcohol addiction.
PMID- 28423642
TI - Correction: Estrogen-dependent downregulation of hypoxia-inducible factor (HIF)
2alpha in invasive breast cancer cells.
PMID- 28423643
TI - POLE and POLD1 screening in 155 patients with multiple polyps and early-onset
colorectal cancer.
AB - Germline mutations in POLE and POLD1 have been shown to cause predisposition to
colorectal multiple polyposis and a wide range of neoplasms, early-onset
colorectal cancer being the most prevalent. In order to find additional mutations
affecting the proofreading activity of these polymerases, we sequenced its
exonuclease domain in 155 patients with multiple polyps or an early-onset
colorectal cancer phenotype without alterations in the known hereditary
colorectal cancer genes. Interestingly, none of the previously reported mutations
in POLE and POLD1 were found. On the other hand, among the genetic variants
detected, only two of them stood out as putative pathogenic in the POLE gene,
c.1359 + 46del71 and c.1420G > A (p.Val474Ile). The first variant, detected in
two families, was not proven to alter correct RNA splicing. Contrarily, c.1420G >
A (p.Val474Ile) was detected in one early-onset colorectal cancer patient and
located right next to the exonuclease domain. The pathogenicity of this change
was suggested by its rarity and bioinformatics predictions, and it was further
indicated by functional assays in Schizosaccharomyces pombe. This is the first
study to functionally analyze a POLE genetic variant outside the exonuclease
domain and widens the spectrum of genetic changes in this DNA polymerase that
could lead to colorectal cancer predisposition.
PMID- 28423644
TI - Disulfide bond disrupting agents activate the unfolded protein response in EGFR-
and HER2-positive breast tumor cells.
AB - Many breast cancer deaths result from tumors acquiring resistance to available
therapies. Thus, new therapeutic agents are needed for targeting drug-resistant
breast cancers. Drug-refractory breast cancers include HER2+ tumors that have
acquired resistance to HER2-targeted antibodies and kinase inhibitors, and
"Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets
Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of
TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR).
Thus agents that selectively kill EGFR+ and HER2+ tumors would provide new
options for breast cancer therapy. We previously identified a class of compounds
we termed Disulfide bond Disrupting Agents (DDAs) that selectively kill EGFR+ and
HER2+ breast cancer cells in vitro and blocked the growth of HER2+ breast tumors
in an animal model. DDA-dependent cytotoxicity was found to correlate with
downregulation of HER1-3 and Akt dephosphorylation. Here we demonstrate that DDAs
activate the Unfolded Protein Response (UPR) and that this plays a role in their
ability to kill EGFR+ and HER2+ cancer cells. The use of breast cancer cell lines
ectopically expressing EGFR or HER2 and pharmacological probes of UPR revealed
all three DDA responses: HER1-3 downregulation, Akt dephosphorylation, and UPR
activation, contribute to DDA-mediated cytotoxicity. Significantly, EGFR
overexpression potentiates each of these responses. Combination studies with DDAs
suggest that they may be complementary with EGFR/HER2-specific receptor tyrosine
kinase inhibitors and mTORC1 inhibitors to overcome drug resistance.
PMID- 28423645
TI - Low forced vital capacity predicts poor prognosis in gastric cancer patients.
AB - Preoperative pulmonary function assessment is used to select surgical candidates
and predict the occurrence of postoperative complications. The present study
enrolled 1210 gastric cancer patients (949 males and 261 females). Forced vital
capacity (FVC) and maximal voluntary ventilation (MVV) were measured as a percent
of predicted values. We then analyzed associations between patient pulmonary
function and both prognosis and postoperative complications. Patient 1-, 3- and 5
year overall survival rates were 88.8%, 65.7% and 53.0%, respectively. FVC and
MVV optimal cutoff values were 87.0 (P=0.003) and 83.6 (P=0.026), respectively.
Low FVC and low MVV were associated with higher rates of postoperative fever
(23.8% vs. 13.9%, P<0.001; 17.8% vs. 13.3%, P=0.049, respectively) and poor
patient prognosis (5-year overall survival: 43.5% vs. 57.6%, P=0.003; 51.8% vs.
54.3%, P=0.026, respectively). Only low FVC was an independent prognostic
predictor for gastric cancer (P=0.012). In subgroup analyses, FVC was not
associated with stage I or II gastric cancer patient prognoses (P>0.05), but low
FVC was an independent risk factor for poor prognosis in stage III gastric cancer
cases (P=0.004). These findings indicate that low FVC is predictive of poorer
prognosis and higher risk of postoperative fever in gastric cancer patients.
PMID- 28423646
TI - TIM-3 is a potential prognostic marker for patients with solid tumors: A
systematic review and meta-analysis.
AB - Accumulated studies have demonstrated the important role of T cell immunoglobulin
and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and
indicated its correlation with patients' survival. To further verify the
prognostic significance of TIM-3 in cancer patients and its correlation with
tumor, we performed this meta-analysis including seven studies searched from
PubMed, Web of Science, and Embase till July 2016. A total of 869 patients were
used to analyze the association between TIM-3 expression and patients' overall
survival (OS). The pooled results showed that higher expression of TIM-3 was
significantly correlated to shorter OS (7 studies, HR=1.89; 95% CI: 1.38-2.57; P<
0.001). In addition, higher TIM-3 expression was associated with advanced tumor
stage (3 studies, III/IV vs. I/II, RR=2.02; 95% CI: 1.45-2.81; P< 0.001). In
conclusion, our study highlights the role of TIM-3 as a potential prognostic
marker and a promising therapeutic target in solid tumors.
PMID- 28423647
TI - Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and
progression of epithelial ovarian carcinoma by regulating activity of ATG3.
AB - Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to
be associated with the pathogenesis of multiple malignancies. However, little is
known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this
study, we found that the expression of Meg3 was lower in epithelial ovarian
carcinoma, and has potential to be considered as a biomarker for ovarian cancer.
After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3,
phenotypic changes and autophagy-related molecules were examined. Upregulation of
Meg3 inhibited cell proliferation, plate colony formation, induced cell cycle
arrest in G2 phases, and promoted apoptosis. Observation of autophagosomes was
performed by transmission electron microscopy. The expression levels of LC3-II,
ATG3, LAMP1 were elevated, while SQSTM1/p62 expression declined. Upregulated
expression of Meg3 also suppressed tumorigenesis in vivo in a xenograft mouse
model through upregulating ATG3 expression. RIP (ribonucleoprotein
immunoprecipitation) and RNA pull-down assays showed that Meg3 was co
immunoprecipitated with ATG3. In addition, Meg3 protected ATG3 mRNA from
degradation following treatment with actinomycin D. Overall, our results suggest
that the lncRNA Meg3 acts as a tumor suppressor in EOC by regulating ATG3
activity and inducing autophagy.
PMID- 28423648
TI - Polyisoprenylated cysteinyl amide inhibitors disrupt actin cytoskeleton
organization, induce cell rounding and block migration of non-small cell lung
cancer.
AB - The malignant potential of Non-Small Cell Lung Cancer (NSCLC) is dependent on
cellular processes that promote metastasis. F-actin organization is central to
cell migration, invasion, adhesion and angiogenesis, processes involved in
metastasis. F-actin remodeling is enhanced by the overexpression and/or hyper
activation of some members of the Rho family of small GTPases. Therefore, agents
that mitigate hyperactive Rho proteins may be relevant for controlling
metastasis. We previously reported the role of polyisoprenylated cysteinyl amide
inhibitors (PCAIs) as potential inhibitors of cancers with hyperactive small
GTPases. In this report, we investigate the potential role of PCAIs against NSCLC
cells and show that as low as 0.5 MUM PCAIs significantly inhibit 2D and 3D NCI
H1299 cell migration by 48% and 45%, respectively. PCAIs at 1 MUM inhibited 2D
and 3D NCI-H1299 cell invasion through Matrigel by 50% and 85%, respectively.
Additionally, exposure to 5 MUM of the PCAIs for 24 h caused at least a 66% drop
in the levels of Rac1, Cdc42, and RhoA and a 38% drop in F-actin intensity at the
cell membrane. This drop in F-actin was accompanied by a 73% reduction in the
number of filopodia per cell. Interestingly, the polyisoprenyl group of the PCAIs
is essential for these effects, as NSL-100, a non-farnesylated analog, does not
elicit similar effects on F-actin assembly and organization. Our findings
indicate that PCAIs disrupt F-actin assembly and organization to suppress cell
motility and invasion. The PCAIs may be an effective therapy option for NSCLC
metastasis and invasion control.
PMID- 28423649
TI - Stellettin B induces apoptosis in human chronic myeloid leukemia cells via
targeting PI3K and Stat5.
AB - Novel agents are still urgently expected for therapy of chronic myeloid leukemia
(CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a
triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562
and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell
proliferation with IC50 as 0.035 MUM and 0.95 MUM respectively. While no obvious
cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B
treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with
increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9. In
addition, dose-dependent increase of reactive oxygen species (ROS) and loss of
mitochondrial membrane potential (MMP) occurred. Meanwhile, Stel B inhibited
phosphorylation of Stat5, expression of 4 PI3K catalytic isoforms, and
phosphorylation of the downstream effectors including PDK1 and Akt, suggesting
that inhibition against Stat5 and PI3K might be involved in the apoptosis
inducing effect. Combination of Stel B with Imatinib with ratio as IC50 Stel B :
5*IC50 Imatinib led to synergistic effect. Stel B might become a promising
candidate for CML therapy alone or together with Imatinib.
PMID- 28423650
TI - MiR-425-5p promotes invasion and metastasis of hepatocellular carcinoma cells
through SCAI-mediated dysregulation of multiple signaling pathways.
AB - MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC)
progression and are key determinants of prognosis. In this study, we found that
miR-425-5p was elevated in HCC and correlated with poor prognostic
clinicopathological features and low post-operative long-term survival.
Multivariate survival analysis indicated that miR-425-5p expression was an
independent risk factor for overall and disease-free survival. Interestingly, miR
425-5p promoted invasion and metastasis by HCC cells, but not HCC cell
proliferation or apoptosis in vitro. SCAI and PTEN were determined to be
downstream targets of miR-425-5p. miR-425-5p-mediated effects were inhibited by
ectopic expression of SCAI, and PTEN exhibited a smaller inhibitory effect. SCAI
also suppressed PTEN expression. In addition, miR-425-5p promoted epithelial-to
mesenchymal transition (EMT), which was antagonized by SCAI. miR-425-5p also
promoted HCC cell invasion and metastasis via SCAI-mediated dysregulation of
integrin beta1-Fak/Src-RhoA/CDC42, PTEN-AKT, and TIMP2-MMP2/MMP9 signaling.
Finally, miR-425-5p promoted metastasis in a xenograft mouse model of HCC. These
results indicate that miR-425-5p facilitates EMT and extracellular matrix
degradation and promotes HCC metastasis through SCAI-mediated dysregulation of
multiple signaling pathways. MiR-425-5p is therefore a potential prognostic
biomarker and novel therapeutic target in HCC.
PMID- 28423651
TI - Succinate dehydrogenase B-deficient cancer cells are highly sensitive to
bromodomain and extra-terminal inhibitors.
AB - Mutations in succinate dehydrogenase B (SDHB) gene are frequently observed in
several tumors and associated with poor prognosis in these tumors. Therefore,
drugs effective for SDHB-deficient tumors could fulfill an unmet medical need. In
addition, such drugs would have an advantage in that selection of patients with
SDHB-mutant cancer could increase the probability of success in clinical trials.
Currently, however, the characteristics of SDHB-deficient cancers are not
completely understood. Here, we established SDHB knockout cancer cell lines from
human colon cancer HCT116 cells using the clustered regularly interspaced short
palindromic repeat (CRISPR)/Cas9 knockout system, and clarified its metabolic
characteristics.In the SDHB knockout cells, succinate was accumulated and
fumarate was decreased. The oxygen consumption rate was decreased while the
extracellular acidification rate was increased in the SDHB knockout cells.
Accordingly, an enhanced glycolysis pathway in the SDHB knockout cells was
demonstrated by metabolomics analysis. Tracer experiments showed bidirectional
metabolic flow in the tricarboxylic acid (TCA) cycle, possibly to maintain the
necessary amounts of metabolites in the SDHB knockout cells. The proliferation of
SDHB knockout cells was suppressed by a glycolysis inhibitor but not by a
mitochondrial inhibitor. Additionally, partial dependence on glutaminolysis was
observed in the SDHB knockout cells. Compound screening revealed that a
bromodomain and extra-terminal (BET) inhibitor, which downregulated c-Myc,
suppressed the growth of the SDHB knockout cells more potently than that of
control cells. These findings provide an understanding of the metabolic
characteristics of SDHB-deficient cancer and its vulnerabilities, which may lead
to new therapeutic options.
PMID- 28423652
TI - Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer
through SPIN1 regulation.
AB - MiR-29 family dysregulation occurs in various cancers including breast cancers.
We investigated miR-29b-1 functional role in human triple negative breast cancer
(TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was
downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1
5p correlated with TNBC regenerative potential, we evaluated cancer stem cell
enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20
produced primary, secondary and tertiary mammospheres, which were progressively
enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression
inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic
overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness
and paclitaxel resistance repressing WNT/betacatenin and AKT signaling pathways
and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b
1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell
lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed
that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1
mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue
by SPIN1miScript protector, determined the reversal of the molecular effects
produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation
impacts on multiple oncogenic features of TNBC cells and their renewal potential,
acting, at least partly, through SPIN1, and suggest that both these factors
should be evaluated as new possible therapeutic targets against TNBC.
PMID- 28423653
TI - A novel microRNA signature predicts survival in stomach adenocarcinoma.
AB - Recent microRNA (miRNA) expression profiling studies suggest the clinical use of
miRNAs as potential prognostic biomarkers in various malignancies. In this study,
aiming to identify microRNAs with prognostic value for overall survival (OS) in
stomach adenocarcinoma (STAD) patients, we analyzed the miRNA expression profiles
and the associated clinical characteristics in 380 STAD samples from The Cancer
Genome Atlas (TCGA) dataset. An eight-miRNA signature for predicting OS in STAD
patients was identified and self-validated by survival analysis and semi
supervised principal components method. We developed a linear prognostic model
composed of these miRNAs to divide patients into high- and low-risk groups
according to the calculated prognostic scores. Kaplan-Meier analysis demonstrated
that patients in the high-risk group had worse OS compared with patients in the
low-risk group. Notably, this miRNA prognostic model showed prognostic
significance to the STAD patients in early stages and the chemo-resistant
patients, who would potentially benefit from additional medical interventions.
Finally, this eight-miRNA signature is an independent prognostic biomarker and
demonstrates a good predictive performance for 5-year survival. Thus, this
signature may serve as a novel biomarker for predicting survival as well as
chemotherapy response in STAD patients.
PMID- 28423654
TI - Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced
senescence.
AB - Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers
and is believed to enhance tumorigenic potential and chemotherapy resistance
through the inhibition of apoptosis and senescence. We previously reported that
Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its
ability to prevent reactive oxygen species (ROS) generation. In this report, we
demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically
mitochondrial ROS, and that these events are upstream of activation of the DNA
damage response, another necessary step toward senescence. Mcl-1's anti
senescence activity also involves the unique ability to inhibit ROS formation by
preventing the upregulation of pro-oxidants. Specifically, we found that NADPH
oxidases (NOXs) are regulated by Mcl-1 and that NOX4 expression in particular is
a required step for CIS induction that is blocked by Mcl-1. Lastly, we illustrate
that by preventing expression of NOX4, Mcl-1 limits its availability in the
mitochondria, thereby lowering the production of mitochondrial ROS during CIS.
Our studies not only define the essential role of Mcl-1 in chemoresistance, but
also for the first time link a key pro-survival Bcl-2 family member with the NOX
protein family, both of which have significant ramifications in cancer
progression.
PMID- 28423655
TI - Sequence-based predictive modeling to identify cancerlectins.
AB - Lectins are a diverse type of glycoproteins or carbohydrate-binding proteins that
have a wide distribution to various species. They can specially identify and
exclusively bind to a certain kind of saccharide groups. Cancerlectins are a
group of lectins that are closely related to cancer and play a major role in the
initiation, survival, growth, metastasis and spread of tumor. Several
computational methods have emerged to discriminate cancerlectins from non
cancerlectins, which promote the study on pathogenic mechanisms and clinical
treatment of cancer. However, the predictive accuracies of most of these
techniques are very limited. In this work, by constructing a benchmark dataset
based on the CancerLectinDB database, a new amino acid sequence-based strategy
for feature description was developed, and then the binomial distribution was
applied to screen the optimal feature set. Ultimately, an SVM-based predictor was
performed to distinguish cancerlectins from non-cancerlectins, and achieved an
accuracy of 77.48% with AUC of 85.52% in jackknife cross-validation. The results
revealed that our prediction model could perform better comparing with published
predictive tools.
PMID- 28423657
TI - Identification and characterization of RASSF1C piRNA target genes in lung cancer
cells.
AB - RASSF1C up-regulates important genes involved in lung cancer cell growth,
including a stem cell self-renewal gene, piwil1. In this article, we report the
identification of small noncoding PIWI-interacting RNAs (piRNAs) in lung cancer
cells over-expressing RASSF1C. A piRNA microarray screen was performed using RNA
isolated from the lung cancer cell line H1299 stably over-expressing RASSF1C and
corresponding control. The piRNA microarray screen identified several piRNAs that
are regulated by RASSF1C and we have validated the expression of two up-regulated
piRNAs (piR-34871 and piR-52200) and two down-regulated piRNAs (piR-35127 and piR
46545) in lung cancer cells with silenced and over-expressed RASSF1C using RT
PCR. We also assessed the expression of these four piRNAs in lung tumor and
matched normal tissues (n = 12). We found that piR-34871 and piR-52200 were up
regulated in 58% and 50%, respectively; while piR-35127 and piR-46545 were down
regulated in 50% in lung tumor tissues tested. The expression of piR-35127 was
inversely correlated with RASSF1C expression in 10/12 tumor tissues. Over
expression of piR-35127 and piR-46545 and knock-down of piR-34871 and piR-52200
significantly reduced normal lung and breast epithelial cell proliferation and
cell colony formation as well as proliferation of lung cancer cell lines (A549
and H1299) and breast cancer cell lines (Hs578T and MDA-MB-231). This suggests
that these novel piRNAs may potentially be involved in regulating lung cell
transformation and tumorigenesis. RASSF1C may potentially modulate the expression
of its piRNA target genes through attenuation of the AMPK pathway, as over
expression of RASSF1C resulted in reduction of p-AMPK, p21, and p27 protein
levels.
PMID- 28423656
TI - Effect of Y6, an epigallocatechin gallate derivative, on reversing doxorubicin
drug resistance in human hepatocellular carcinoma cells.
AB - Cancer cells can acquire resistance to a wide variety of diverse and unrelated
drugs, this phenomenon is termed multidrug resistance (MDR). Multidrug resistance
has been an obstacle to the success of cancer chemotherapy. The present study
investigated the reversal effect of Y6, a new compound obtained by chemically
modifying the structure of epigallocatechin-3-gallate (EGCG) extracted from green
tea. Y6 was proven to be effective in inhibiting cell proliferation and reversing
drug resistance in doxorubicin (DOX) resistant human hepatocellular carcinoma
cells (BEL-7404/DOX). BEL-7404/DOX cells were treated with either doxorubicin
combination regimen (doxorubicin plus Y6 or epigallocatechin-3-gallate or
verapamil separately) or doxorubicin alone. The results showed that cell
proliferation was inhibited and late cell apoptosis increased in the combination
treatment group, especially in the group treated with doxorubicin plus Y6.
Further analysis revealed that the expressions of hypoxia-inducible factor-1alpha
and multidrug resistance 1/P-glycoprotein decreased at both messenger RNA and
protein levels by treatments with combined drugs compared to doxorubicin alone.
Our results indicated that Y6, as a drug resistance reversal agent, increased the
sensitivity of drug resistant cells to doxorubicin. The mechanisms of actions of
Y6 in reversal effect were associated with the decreased expression of hypoxia
inducible factor-1alpha and multidrug resistance 1/P-glycoprotein.
PMID- 28423658
TI - Correlation between polymorphisms in microRNA-regulated genes and cervical cancer
susceptibility in a Xinjiang Uygur population.
AB - We explored the correlation between single nucleotide polymorphisms (SNPs) and
susceptibility to cervical cancer (CC) in a Xinjiang Uygur population. Ten SNPs
in eight miRNA-regulated genes were selected for analysis. Odds ratios (ORs) and
95% confidence intervals (95% CIs) were calculated using unconditional logistic
regression analysis. Multivariate logistic regression analysis was used to detect
correlations between SNPs and CC. We found that minor allele "C" of rs512715 in
NEAT1 was associated with an increased risk of CC in the allele, codominant,
dominant, overdominant and log-additive models. Minor allele "C" of rs4777498 in
CELF6 was associated with an increased risk of CC in the recessive model. Minor
allele "C" of rs3094 in RNASE4 was associated with increased risk of CC in the
allele, dominant and log-additive models. In clinical stage III/IV CC patients,
minor allele "C" of rs3094 in RNASE4 and minor allele "C" of rs8004334 in JDP2
were associated with increased risk. In subtype squamous carcinoma CC patients,
minor allele "C" of rs512715 in NEAT1 and minor allele "C" of rs3094 in RNASE4
were associated with increased risk. In subtype adenocarcinoma CC patients, minor
allele "C" of rs3094 in RNASE was associated with increased risk.
PMID- 28423659
TI - Targeting HOX/PBX dimers in cancer.
AB - The HOX and PBX gene families encode transcription factors that have key roles in
establishing the identity of cells and tissues in early development. Over the
last 20 years it has become apparent that they are also dysregulated in a wide
range of solid and haematological malignancies and have a predominantly pro
oncogenic function. A key mode of transcriptional regulation by HOX and PBX
proteins is through their interaction as a heterodimer or larger complex that
enhances their binding affinity and specificity for DNA, and there is growing
evidence that this interaction is a potential therapeutic target in malignancies
that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma,
and acute myeloid leukaemia. This review summarizes the roles of HOX and PBX
genes in cancer and assesses the therapeutic potential of HOX/PBX dimer
inhibition, including the availability of biomarkers for its application in
precision medicine.
PMID- 28423660
TI - Progerin impairs vascular smooth muscle cell growth via the DNA damage response
pathway.
AB - Mutations of the lamin A gene cause various premature aging syndromes, including
Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner syndrome. In HGPS
(but not atypical Werner syndrome), extensive loss of vascular smooth muscle
cells leads to myocardial infarction with premature death. The underlying
mechanisms how single gene mutations can cause various phenotypes are largely
unknown. We performed an interactome analysis using mutant forms of lamin A
involved in progeroid syndromes. We found that the mutant lamin A responsible for
HGPS, known as progerin, could not bind to proteins related to the DNA damage
response, including DNA-dependent protein kinase (DNA-PK). In contrast, wild-type
lamin A and lamin A mutants causing atypical Werner syndrome were able to bind to
these molecules. We also found that forced expression of progerin in vascular
smooth muscle cells led to activation of DNA-PK and cellular growth arrest, while
knockdown of DNA-PK attenuated this. Deletion of p53 also improved the inhibition
of cell growth due to forced expression of progerin. These findings suggested
that progerin activates the DNA damage response pathway and that dysregulation of
this pathway may be responsible for the development of cardiovascular pathology
in patients with HGPS.
PMID- 28423661
TI - Examining the association between anthropometric parameters and telomere length
and mortality risk.
AB - A shorter telomere length is associated with several systemic disorders. Telomere
length may be an informative biomarker for the maintenance of the overall health
status and mortality. There are a limited number of empirical studies concerning
the effect of anthropometric parameters on telomere length. The data are derived
from the National Health and Nutrition Examination Survey from 1999 to 2002. The
primary outcomes of this study were to examine the potential relationships
between the anthropometric indices and the telomere length, while secondary
outcomes of this study was to investigate the association between different
anthropometric indices and mortality risk. A significant positive correlation was
noted between the mean telomere length and the thigh circumference (TC) and calf
circumference (CC) in all designed models. Participants in the highest TC and CC
quartiles tended to have a longer telomere length and lowered the hazards for all
cause mortality to 43% and 57%, respectively. Notably, the anthropometric indices
involving the CC with higher values seemed to be surrogate markers for the
reduction of the risk of all-cause, cardiovascular and malignancy-related
mortality (all P < 0.05). The CCmay be a valuable tool to guide public health
policy and a clinical prognostic indicator for the risk of mortality.
PMID- 28423662
TI - Comparative analysis of HPV16 gene expression profiles in cervical and in
oropharyngeal squamous cell carcinoma.
AB - Human papillomavirus type 16 (HPV16) is the major cause of cervical cancer and of
a fraction of oropharyngeal carcinoma. Few studies compared the viral expression
profiles in the two types of tumor. We analyzed HPV genotypes and viral load as
well as early (E2/E4, E5, E6, E6*I, E6*II, E7) and late (L1 and L2) gene
expression of HPV16 in cervical and oropharyngeal cancer biopsies. The study
included 28 cervical squamous cell carcinoma (SCC) and ten oropharyngeal SCC,
along with pair-matched non-tumor tissues, as well as four oropharynx dysplastic
tissues and 112 cervical intraepithelial neoplasia biopsies. Viral load was found
higher in cervical SCC (<1 to 694 copies/cell) and CIN (<1 to 43 copies/cell)
compared to oropharyngeal SCC (<1 to 4 copies/cell). HPV16 E2/E4 and E5 as well
as L1 and L2 mRNA levels were low in cervical SCC and CIN and undetectable in
oropharynx cases. The HPV16 E6 and E7 mRNAs were consistently high in cervical
SCC and low in oropharyngeal SCC. The analysis of HPV16 E6 mRNA expression
pattern showed statistically significant higher levels of E6*I versus E6*II
isoform in cervical SCC (p = 0.002) and a slightly higher expression of E6*I
versus E6*II in oropharyngeal cases. In conclusion, the HPV16 E5, E6, E6*I, E6*II
and E7 mRNA levels were more abundant in cervical SCC compared to oropharyngeal
SCC suggesting different carcinogenic mechanisms in the two types of HPV-related
cancers.
PMID- 28423665
TI - IL-33-induced alternatively activated macrophage attenuates the development of
TNBS-induced colitis.
AB - Accumulated data have shown that alternatively activated macrophage exerts a
modulatory role in many diseases, including colitis. Interleukin-33 (IL-33), a
critical modulator in adaptive and innate immune, has been implicated in
autoimmunity and inflammation. Previously, we have reported that IL-33 functions
as a protective modulator in TNBS-induced colitis, which is closely related to a
Th1-to-Th2/Treg switch. Here, we present novel evidence suggesting that IL-33
primes macrophage into alternatively activated macrophages (AAM) in TNBS-induced
colitis. The strong polarized effect of IL-33 was tightly associated with the
markedly increased induction of Th2-type cytokines. To confirm the beneficial
effects of AAM induced by IL-33, peritoneal AAMs isolated from IL-33-treated mice
were transferred to recipient mice with TNBS colitis. The adoptive transfer
resulted in prominent inhibition of disease activity and inflammatory cytokines
in the TNBS-treated mice. In conclusion, our data provide clear evidence that IL
33 plays a protective role in TNBS-induced colitis, which is closely related to
AAM polarization.
PMID- 28423666
TI - Negative LC3b immunoreactivity in cancer cells is an independent prognostic
predictor of prostate cancer specific death.
AB - BACKGROUND: Autophagy is a catabolic cellular process used for degradation of
cytoplasmic organelles and preservation of cell viability. In this study we aimed
to analyse the level of autophagy markers in benign and malignant prostate tissue
and to evaluate the prognostic properties for patients with prostate cancer
(PCa). RESULTS: LC3b expression was significantly upregulated in PCa, especially
in metastatic and castration-resistant PCa samples compared to benign prostate
tissue (p<0.001). Evaluation of expression in malignant radical prostatectomy
specimens revealed an inverse association with preoperative serum PSA levels
(p=0.02) and Gleason Score (p=0.07). LC3b immunoreactivity was identified as a
novel predictor of PCa specific death after radical prostatectomy, independent of
Gleason score, tumour stage, and surgical margin status in a multivariable cox
regression analysis (hazard ratio 0.09, 95% confidence interval 0.01-0.69,
p=0.021). A significant association of ATG-5 and Beclin 1 with LC3b expression
could be noticed (p<0.001), but no link with other clincopathologic parameters
was observed. METHODS: A Tissue microarray containing 468 formalin-fixed,
paraffin-embedded prostate tissue cores was stained immunohistochemically for
major autophagy proteins LC3b, ATG5 and Beclin 1. Immunoreactivity was
semiquantitatively scored and correlated with pathologic and clinical parameters,
including tumour stage, Gleason score, preoperative PSA level, biochemical
recurrence rate and survival. The median clinical follow-up was 132 months.
CONCLUSION: LC3b was significantly overexpressed in malignant compared to benign
prostate tissue. However, positive LC3b immunoreactivity in PCa, as a marker of
increased autophagy, was independently associated with a reduced disease-specific
mortality.
PMID- 28423667
TI - Saline is a more appropriate solution for microvesicles for flow cytometric
analyses.
AB - Microvesicles (MVs) are carriers of molecular and oncogenic signatures present in
subsets of tumor cells and tumor-associated stroma, and a focus of cancer
research. Although methods to detect MVs are mature, we were concerned that the
buffer used could lead to false results when quantitating MVs by flow cytometry.
In this work,we detected MVs by flow cytometry withthree different solutions:
water, saline, and phosphate-buffered saline (PBS). The results demonstrated that
PBS, when reacted with annexin V binding buffer, produced nano-sized vesicles
even when there were no MVs in the sample. No similar events occurred in the
saline and water groups (P < 0.01). Annexin V positive rate increased
significantly when PBS was used as the buffer, compared to saline and water.
These false negative results were also observed when we quantified some markers
of MVs such as CD3 and CD19. A probable explanation for these findings is the
production of insoluble Ca(H2PO4)2 or Ca3PO4 from calcium in the binding buffer
and phosphate in PBS. Thus, considering the osmotic pressure of water, we suggest
that saline is a more suitable buffer when counting MVs by flow cytometry.
PMID- 28423668
TI - AHNAK2 is a potential prognostic biomarker in patients with PDAC.
AB - BACKGROUND: AHNAK nucleoprotein 2 (AHNAK2) belongs to the AHNAK protein family.
The studies of AHNAK2 are limited. A recent study reported that AHNAK2 might be a
biomarker for pancreatic ductal adenocarcinoma (PDAC); however, tissue-based
experiments have not been conducted. The aim of this study was to determine the
tissue expression of AHNAK2 and to find the correlation between AHNAK2 and
overall survival rate in PDAC. RESULTS: AHNAK2 is highly expressed in PDAC (n=79)
compared with adjacent normal tissues (n=64, P<0.001). Overexpression of AHNAK2
showed a significant relationship with a lower overall survival rate (P=0.033) in
PDAC patients. The predictive value of increased expression of AHNAK2 remains
relevant in patients with AJCC grade above II (n=43, P=0.006) or lymph node
metastasis (n=32, P=0.004). Cox regression analysis showed that AHNAK2 expression
(P=0.003) and pathology grade (P<0.001) are independent prognostic factors for
PDAC. The nomogram model was performed to predict the 1- and 3-year survival
rates based on Cox regression. The C-index was 0.61. The calibration curves were
also made to show the association between the observed and predicted probability
of the overall survival rates. MATERIALS AND METHODS: AHNAK2 expression was
performed in tissue microarrays by immunohistochemistry. The overall survival
rate analysis was performed using the Kaplan-Meier method, Cox proportional
hazards regression, and a nomogram model. CONCLUSIONS: AHNAK2 is overexpressed in
PDAC tissues and is an independent prognostic factor in patients with PDAC.
PMID- 28423669
TI - The novel long non-coding RNA TALNEC2, regulates tumor cell growth and the
stemness and radiation response of glioma stem cells.
AB - Despite advances in novel therapeutic approaches for the treatment of
glioblastoma (GBM), the median survival of 12-14 months has not changed
significantly. Therefore, there is an imperative need to identify molecular
mechanisms that play a role in patient survival. Here, we analyzed the expression
and functions of a novel lncRNA, TALNEC2 that was identified using RNA seq of
E2F1-regulated lncRNAs. TALNEC2 was localized to the cytosol and its expression
was E2F1-regulated and cell-cycle dependent. TALNEC2 was highly expressed in GBM
with poor prognosis, in GBM specimens derived from short-term survivors and in
glioma cells and glioma stem cells (GSCs). Silencing of TALNEC2 inhibited cell
proliferation and arrested the cells in the G1?S phase of the cell cycle in
various cancer cell lines. In addition, silencing of TALNEC2 decreased the self
renewal and mesenchymal transformation of GSCs, increased sensitivity of these
cells to radiation and prolonged survival of mice bearing GSC-derived xenografts.
Using miRNA array analysis, we identified specific miRNAs that were altered in
the silenced cells that were associated with cell-cycle progression,
proliferation and mesenchymal transformation. Two of the downregulated miRNAs,
miR-21 and miR-191, mediated some of TALNEC2 effects on the stemness and
mesenchymal transformation of GSCs. In conclusion, we identified a novel E2F1
regulated lncRNA that is highly expressed in GBM and in tumors from patients of
short-term survival. The expression of TALNEC2 is associated with the increased
tumorigenic potential of GSCs and their resistance to radiation. We conclude that
TALNEC2 is an attractive therapeutic target for the treatment of GBM.
PMID- 28423670
TI - Invasive Fusobacterium nucleatum activates beta-catenin signaling in colorectal
cancer via a TLR4/P-PAK1 cascade.
AB - The underlying mechanism of Fusobacterium nucleatum (Fn) in the carcinogenesis of
colorectal cancer (CRC) is poorly understood. Here, we examined Fn abundance in
CRC tissues, as well as beta-catenin, TLR4 and PAK1 protein abundance in Fn
positive and Fn negative CRCs. Furthermore, we isolated a strain of Fn (F01) from
a CRC tissue and examined whether Fn (F01) infection of colon cancer cells
activated beta-catenin signaling via the TLR4/P-PAK1/P-beta-catenin S675 cascade.
Invasive Fn was abundant in 62.2% of CRC tissues. TLR4, PAK1 and nuclear beta
catenin proteins were more abundant within Fn-positive over Fn-negative CRCs (P <
0.05). Fn and its lipopolysaccharide induced a significant increase in TLR4/P
PAK1/P-beta-catenin S675/C-myc/CyclinD1 protein abundance, as well as in the
nuclear translocation of beta-catenin. Furthermore, inhibition of TLR4 or PAK1
prior to challenge with Fn significantly decreased protein abundance of P-beta
catenin S675, C-myc and Cyclin D1, as well as nuclear beta-catenin accumulation.
Inhibition of TLR4 significantly decreased P-PAK1 protein abundance, and for the
first time, we observed an interaction between TLR4 and P-PAK1 using
immunoprecipitation. Our data suggest that invasive Fn activates beta-catenin
signaling via a TLR4/P-PAK1/P-beta-catenin S675 cascade in CRC. Furthermore, TLR4
and PAK1 could be potential pharmaceutical targets for the treatment of Fn
related CRCs.
PMID- 28423671
TI - Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic
cancer.
AB - Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United
States with a five-year patient survival rate of only 6%. Early detection and
treatment of this disease is hampered due to lack of reliable diagnostic and
prognostic markers. Recent studies have shown that dynamic changes in the global
DNA methylation and gene expression patterns play key roles in the PC
development; hence, provide valuable insights for better understanding the
initiation and progression of PC. In the current study, we used DNA methylation,
gene expression, copy number, mutational and clinical data from pancreatic
patients. We independently investigated the DNA methylation and differential gene
expression profiles between normal and tumor samples and correlated methylation
levels with gene expression patterns. We observed a total of ~23-thousand
differentially methylated CpG sites (Deltabeta>=0.1) between normal and tumor
samples, where majority of the CpG sites are hypermethylated in PC, and this
phenomenon is more prominent in the 5'UTRs and promoter regions compared to the
gene bodies. Differential methylation is observed in genes associated with the
homeobox domain, cell division and differentiation, cytoskeleton, epigenetic
regulation and development, pancreatic development and pancreatic signaling and
pancreatic cancer core signaling pathways. Correlation analysis suggests that
methylation in the promoter region and 5'UTR has mostly negative correlations
with gene expression while gene body and 3'UTR associated methylation has
positive correlations. Regulatory element analysis suggests that HOX cluster and
histone core proteins are upstream regulators of hypomethylation, while SMAD4,
STAT4, STAT5B and zinc finger proteins (ZNF) are upstream regulators of
hypermethylation. Non-negative matrix factorization (NMF) clustering of
differentially methylated sites generated three clusters in PCs suggesting the
existence of distinct molecular subtypes. Cluster 1 and cluster 2 showed samples
enriched with clinical phenotypes like neoplasm histological grade and pathologic
T-stage T3, respectively, while cluster 3 showed the enrichment of samples with
neoplasm histological grade G1. To the best of our knowledge, this is the first
genome-scale methylome analysis of PC data from TCGA. Our clustering analysis
provides a strong basis for future work on the molecular subtyping of epigenetic
regulation in pancreatic cancer.
PMID- 28423672
TI - alpha2,3-sialyltransferase type I regulates migration and peritoneal
dissemination of ovarian cancer cells.
AB - Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic
cancers due to advanced stage presentation, peritoneal dissemination, and
refractory ascites at diagnosis. We investigated the role of alpha2,3
sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and
human EOC tissue arrays. We found that high expression of ST3GalI was associated
with advanced stage EOC. Transwell migration and cell invasion assays showed that
high ST3GalI expression enhanced migration of EOC cells. We also observed that
there was a linear relation between ST3GalI expression and epidermal growth
factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI
expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation
experiments demonstrated that ST3GalI and EGFR were present in the same protein
complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I
(SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse
model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the
anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that
ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via
EGFR signaling. This suggests alpha2,3-linked sialylation inhibitors in
combination with EGFR inhibitors could be effective agents for the treatment of
EOC.
PMID- 28423673
TI - Ceruloplasmin as a prognostic marker in patients with bile duct cancer.
AB - BACKGROUND AND AIMS: Bile duct cancer is one of the lethal cancers, presenting
difficulties in early diagnosis and limited treatment modalities. Despite current
advances in biomarker research, most studies have been performed in Western
populations. Therefore, the purpose of this study was to determine a prognostic
marker for bile duct cancer, especially in Korean patients, whose incidence of
bile duct cancer is high. RESULTS: Comparing cancer and normal bile duct tissue,
we identified 29091 differentially expressed genes. CP, SCEL, and MUC16 had
positive coefficients with a log2 ratio >1 for advanced T, N stage and perineural
invasion cancer tissue. Strong immunohistochemical expression of ceruloplasmin
was dominant in tumors with advanced T stage (p>0.999) and perineural invasion
(p=0.316). PATIENTS AND METHODS: We performed tissue microarray experiment with
79 bile duct cancer tissue samples and 21 normal bile duct tissue samples.
Candidate genes that has positive correlation with T, N stage and perineural
invasion were drawn with multivariate analysis. Tissue expression of the genes
was evaluated with an immunohistochemical study. CONCLUSIONS: Ceruloplasmin is
supposed to be related with advanced T stage and perineural invasion, having a
possibility as a candidate prognostic marker for bile duct cancer.
PMID- 28423674
TI - A single center clinical analysis of children with high-risk neuroblastoma.
AB - : The current multidisciplinary treatment for patients with high-risk
neuroblastoma (NB) is the common census. However, protocols and opinions are
different in different regions and institutions. We aimed to assess the protocol
formulated by Chinese Children's Cancer Group study in 2009, and the impact of
surgery extent was highlightly evaluated. METHODS: This study enrolled patients
with high-risk neuroblastoma between 2009 and 2014 in Department of Pediatric
Oncology of Tianjin Medical University Cancer Institute and Hospital. The
clinical characteristics of patients were illustrated and surgery extent was
evaluated by the impact on survival rate. RESULTS: The 3-year overall survival
(OS) and progression-free survival (PFS) were 56.2% and 50.5%, respectively. LDH
(P<0.001), bone marrow metastasis at time of diagnosis (P=0.001), bone marrow
negative after neoadjuvant chemotherapy (P<0.001), radiotherapy (P<0.001) were
significant predictors of OS and PFS. And surgery extent had no impact on the
enhancement of high-risk neuroblastoma patients in short time. CONCLUSIONS: This
study showed no substantial survival benefit in patients with high-risk NB
undergoing gross total tumor resection. Multidisciplinary intensive treatment was
essential, especially for patients received subtotal tumor resection. Longer term
follow-up is needed to survey complications in surviving patients who received
intensive chemotherapy and radiotherapy.
PMID- 28423675
TI - miR-219-5p targets CaMKIIgamma to attenuate morphine tolerance in rats.
AB - Morphine tolerance is a clinical challenge in pain management. Emerging evidence
suggests that microRNA (miRNA) plays a regulatory role in the development of
morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein
kinase II gamma (CaMKIIgamma) to activate central pain sensitization via N-methyl
D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p
attenuates morphine tolerance by targeting CaMKIIgamma. We found that the
expression of miR-219-5p was decreased significantly after chronic morphine
treatment. Overexpression of miR-219-5p by lentivirus injection prevents the
development of morphine tolerance. CaMKIIgamma, the target gene of miR-219-5p was
downregulated by overexpression of miR-219-5p both in vivo and in vitro.
Furthermore, we found that lentiviral-mediated miR-219-5p decreased the
expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine
tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in
alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway.
Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine
tolerance.
PMID- 28423676
TI - Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial
mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation.
AB - Tumor-associated macrophages (TAMs) are key components of tumor microenvironment
(TME) during tumorigenesis and progression. However, the role of TAMs in lung
adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism
underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT)
of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer
sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it
plays critical role in the invasion and metastasis. Here, we found that in lung
adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and
LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through
the transforming growth factor-beta1(TGF-beta1)/Smad2/3 signaling pathway.
FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and
EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the
phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages
induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through
the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed
that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma
through FUT4/LeY- mediated fucosylation. Targeting this newly identified
signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.
PMID- 28423677
TI - Identifying the structure-activity relationship of leelamine necessary for
inhibiting intracellular cholesterol transport.
AB - Leelamine is an anticancer chemotherapeutic agent inhibiting intracellular
cholesterol transport. Cell death mediated by leelamine occurs due to the
lysosomotropic property of the compound, its accumulation in the lysosome, and
inhibition of cholesterol transport leading to lack of availability for key
processes required for functioning of cancer cells. The present study dissects
the structure-activity-relationship of leelamine using synthesized derivatives of
leelamine and abietic acid, a structurally similar compound, to identify the
moiety responsible for anti-cancer activity. Similar to leelamine, all active
derivatives had an amino group or a similar moiety that confers a lysosomotropic
property to the compound enabling its accumulation in the lysosome. Active
derivatives inhibited intracellular cholesterol transport and hindered
xenografted melanoma tumor development without obvious systemic toxicity. In
silico studies suggested that active derivatives accumulating in lysosomes bound
to NPC1, a protein responsible for cholesterol export from the lysosome, to
inhibit its activity that then caused accumulation, and lack of cholesterol
availability for other key cellular activities. Thus, active derivatives of
leelamine or abietic acid maintained lysosomotropic properties, bound to NPC1,
and disrupted cellular cholesterol transport as well as availability to retard
tumor development.
PMID- 28423678
TI - Influence of ipilimumab on expanded tumour derived T cells from patients with
metastatic melanoma.
AB - INTRODUCTION: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy
(ACT) is a promising treatment for patients with advanced melanoma. Retrospective
studies suggested an association between previous treatment with anti-CTLA-4
antibodies and long term survival after subsequent ACT. Thus, we hypothesized
that treatment with anti-CTLA-4 antibodies can induce favourable changes to be
detected in TILs. RESULTS: Expanded T cells from Ipilimumab treated patients had
a higher proportion of cells expressing CD27, intracellular CTLA-4, TIM-3 and LAG
3. In addition, broader and more frequent T cell responses against common tumour
antigens were detected in patients treated with Ipilimumab as compared to anti
CTLA-4 naive patients. MATERIALS AND METHODS: Expanded TILs were obtained from
patients with advanced melanoma who had received Ipilimumab in the previous six
months, or had not received any type of anti-CTLA-4 antibody. T cell specificity
and expression of phenotypic and exhaustion markers were scrutinized as well as
functional properties. CONCLUSIONS: Ipilimumab may induce tumor-infiltration of T
cells of a more naive phenotype expressing markers related to activation or
exhaustion. Additionally, Ipilimumab may increase the frequency of T cells
recognizing common tumour associated antigens.
PMID- 28423679
TI - Association of IL-1A and IL-1B polymorphisms with ankylosing spondylitis among
the Chinese Han population: a case-control study.
AB - Ankylosing spondylitis (AS) is a complex and chronic inflammatory disease with a
high heritage. Previous study has shown that IL-1A and IL-1B involved in
inflammatory reaction. But little is known about single nucleotide polymorphisms
(SNPs) of IL-1A and IL-1B associated with AS. We conducted a case-control study
among 267 AS cases and 297 healthy controls from China. In the genetic model
analysis, we found the "T" genotype of rs3783550 was associated with decreased AS
risk in the dominant model (p = 0.044) and log-additive model (p = 0.023); the
"C" genotype of rs3783546 was significantly associated with decreased AS risk
based in the dominant model (p = 0.044) and log-additive model (p = 0.023).
Additionally, the minor allele "A" of rs2853550 may also reduce the risk of AS in
dominant (p = 0.025) and log-additive model (p = 0.024). Our results suggested
that the polymorphisms of IL-1A and IL-1B are associated with the AS
susceptibility in the Chinese Han population. Further studies are needed to
characterize the functional sequences that cause AS.
PMID- 28423680
TI - A bioartificial dermal regeneration template promotes skin cell proliferation in
vitro and enhances large skin wound healing in vivo.
AB - A novel bioartificial dermal regeneration template has been developed using
platelet-rich plasma and acellular animal skin collagen sponge for the treatment
of larger area and full thickness skin wounds. This platelet-rich plasma-collagen
sponge keeps native skin structure and contains huge amounts of growth factors.
The effect of this bioartificial dermal regeneration template was tested in vitro
and in vivo via a mimic poor wound healing process by adding collagenase I into
cell culture medium or the wound area. The in vitro experimental results
indicated that the rat skin cells grew faster and produced more collagen in
platelet-rich plasma-collagen sponge with collagenase than those treated either
with collagen sponge plus collagenase, or collagenase, or control group without
treatment. The in vivo experiments were performed by large rat skin wounds, 1.5
cm diameter, treated either with collagenase, or collagenase plus collagen
sponge, or collagenase plus platelet-rich plasma-collagen sponge. The wound
without treatment was used as a control. The wounds treated with collagenase
containing platelet-rich plasma-collagen sponge healed 4 times faster than the
untreated wounds, 6 times faster than the collagenase treated wounds, 2.4 times
faster than collagenase-containing collagen sponge treated wounds. The
immunostaining indicated that the healed tissues in the wound areas treated with
collagenase-containing platelet-rich plasma-collagen sponge were composed of
collagen type I and collagen III with blood vessels and hair follicles. The
results demonstrated that this collagenase-containing platelet-rich plasma
collagen sponge works as a bioartificial dermal regeneration template. The
application of this collagenase-containing platelet-rich plasma-collagen sponge
promotes the traumatic skin wound healing and permits the reconstitution of the
inherent barrier functions of the skin.
PMID- 28423681
TI - Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism
targeted approach.
AB - The clinical course for both early and late stage Bladder Cancer (BC) continues
to be characterized by significant patient burden due to numerous occurrences and
recurrences requiring frequent surveillance strategies, intravesical drug
therapies, and even more aggressive treatments in patients with locally advanced
or metastatic disease. For these reasons, BC is also the most expensive cancer to
treat. Fortunately, BC offers an excellent platform for chemoprevention
interventions with potential to optimize the systemic and local exposure of
promising agents to the bladder mucosa. However, other than smoking cessation,
there is a paucity of research that systematically examines agents for
chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism
based approach, the goal of this review is to summarize epidemiological, in
vitro, and preclinical studies, including data regarding the safety,
bioavailability, and efficacy of agents evaluated for bladder cancer
chemoprevention. Based on the available studies, phytochemicals, specifically
isothiocyanates such as sulforaphane, present in Brassicaceae or "cruciferous"
vegetables in the precursor form of glucoraphanin are: (a) available in
standardized formulations; (b) bioavailable- both systemically and in the
bladder; (c) observed to be potent inhibitors of BC carcinogenesis through
multiple mechanisms; and (d) without toxicities at these doses. Based on
available evidence from epidemiological, in vitro, preclinical, and early phase
trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane
(SFN) represent a promising potential chemopreventitive agent in bladder cancer.
PMID- 28423682
TI - RIP3 deficiency ameliorates inflammatory response in mice infected with influenza
H7N9 virus infection.
AB - Influenza H7N9 virus infection causes an acute, highly contagious respiratory
illness that triggers cell death of infected cells and airway epithelial
destruction. RIP3 is a key regulator of cell death responses to a growing number
of viral and microbial agents. This study aimed to investigate the role of RIP3
in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-)
mice and littermate wild type mice were infected intranasally with influenza H7N9
virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the
inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/
mice infected with H7N9 virus showed higher survival and less weight loss,
compared with wild type littermate mice. In addition, RIP3-/- mice had fewer
regions of edema, infiltration with inflammatory cells, and alvelolar collapses,
and the secretions of IL-1beta, IL-6, RANTES and MIP-1 in BALF were significantly
decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase
1/IL1beta signaling was found to be invovled in RIP3 associated imflammation of
influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion,
our results indicated that RIP3 deficiency can protect mice from the infection of
influenza H7N9 virus by downregulating caspase 1/IL1beta signaling, which
provided edivence of the RIP3 invovled necroptosis independent manner.
PMID- 28423683
TI - The potential roles of aquaporin 4 in malignant gliomas.
AB - Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous
system and is primarily expressed in astrocytes. Recently, accumulated evidence
has pointed to AQP4 as a key molecule that could play a critical role in glioma
development. Discoveries of the role of AQP4 in cell migration suggest that AQP4
could be a significant factor regarding glioma malignancies. However, the AQP4
expression levels in glioma have not been fully elucidated; furthermore, the
correlation of AQP4 expression with glioma malignancy remains controversial.
Here, we review the expression pattern and predictive significance of AQP4 in
malignant glioma. The molecular mechanism of AQP4 as it pertains to the migration
and invasion of human glioma cells has been summarized. In addition, the
important roles of AQP4 in combating drug resistance as well as potential
pharmacological blockers of AQP4 have been systematically discussed. More
research should be conducted to elucidate the potential roles of AQP4 in
malignant glioma for identifying the tumor type, progression stages and optimal
treatment strategies. The observed experimental results strongly emphasize the
importance of this topic for future investigations.
PMID- 28423685
TI - Tumor-fibroblast interactions stimulate tumor vascularization by enhancing
cytokine-driven production of MMP9 by tumor cells.
AB - Advance-stage breast carcinomas include significant amounts of fibroblasts and
infiltrating immune cells which have been implicated in tumor growth, recurrence,
and response to therapy. The present study investigated the contribution of
fibroblasts to tumor growth using direct tumor-fibroblast co-cultures and tumor
xenograft models. Our findings revealed that fibroblasts enhance breast carcinoma
growth by promoting the tumor vasculature via the MMP9-dependent mechanism. In
tumor-fibroblast co-cultures, fibroblasts increased expression of TGF-beta, TNF,
and IL-1beta cytokines in tumor cells. These cytokines cooperatively induced
expression of matrix metalloproteinase MMP9 in tumor cells. Knockdown of MMP9 by
shRNA significantly reduced tumor vascularization induced by fibroblasts.
Mechanistically, our findings argue that expression of MMP9 in tumor cellsis
regulated by crosstalk of TGF-beta with TNF and/or IL-1beta cytokines. The
mechanism of this cooperative response did not involve cross-activation of the
canonical signaling pathways as TGF-beta did not activate RELA/p65 signaling,
while TNF did not affect SMAD signaling. Instead, TGF-beta and TNF cytokines co
stimulated MAP kinases and expression of JUN and JUNB, AP1 transcription factor
subunits, which together with RELA/p65 were essential for the regulation of MMP9.
Depletion of JUN and JUNB or RELA in tumor cells blocked the cooperative
induction of MMP9 by the cytokines. Thus, our studies uncovered a previously
unappreciated role of tumor-fibroblast interactions in the stimulation of tumor
angiogenesis, and an essential role of the MAPK-AP1 axis in the cooperative up
regulation of the angiogenic driver MMP9 by cytokine crosstalk.
PMID- 28423688
TI - MicroRNAs in biofluids are novel tools for bladder cancer screening.
AB - MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in basic
cellular processes, including differentiation, proliferation, apoptosis and
autophagy. They are also involved in various stages of tumorigenesis and play key
roles in bladder cancer initiation and progression. Notably, the altered
expression of miRNAs in the tumors is reflected in body fluids, including blood
and urine, which opens avenues for non-invasive diagnosis and prognosis. Many
studies have demonstrated that epigenetic changes extensively alter tumoral
microRNA expression. The high reproducibility, specificity and sensitivity of
miRNA levels in body fluids suggest their potential use as biomarkers for cancer
screening and diagnosis. For example, recent technological advances have made it
possible to detect miRNAs in urine for bladder cancer screening. In this review,
we focus mainly on the current knowledge and future challenges for incorporating
miRNAs in body fluids, like urine and blood, for making clinical diagnoses and
assessing prognoses in bladder cancer.
PMID- 28423690
TI - PreImplantation factor (PIF) protects cultured embryos against oxidative stress:
relevance for recurrent pregnancy loss (RPL) therapy.
AB - Recurrent pregnancy loss (RPL) affects 2-3% of couples. Despite a detailed work
up, the etiology is frequently undefined, leading to non-targeted therapy. Viable
embryos and placentae express PreImplantation Factor (PIF). Maternal circulating
PIF regulates systemic immunity and reduces circulating natural killer cells
cytotoxicity in RPL patients. PIF promotes singly cultured embryos' development
while anti-PIF antibody abrogates it. RPL serum induced embryo toxicity is
negated by PIF. We report that PIF rescues delayed embryo development caused by
<3 kDa RPL serum fraction likely by reducing reactive oxygen species (ROS). We
reveal that protein disulfide isomerase/thioredoxin (PDI/TRX) is a prime PIF
target in the embryo, rendering it an important ROS scavenger. The 16F16-PDI/TRX
inhibitor drastically reduced blastocyst development while exogenous PIF
increased >2 fold the number of embryos reaching the blastocyst stage.
Mechanistically, PDI-inhibitor preferentially binds covalently to oxidized PDI
over its reduced form where PIF avidly binds. PIF by targeting PDI/TRX at a
distinct site limits the inhibitor's pro-oxidative effects. The >3kDa RPL serum
increased embryo demise by three-fold, an effect negated by PIF. However, embryo
toxicity was not associated with the presence of putative anti-PIF antibodies.
Collectively, PIF protects cultured embryos both against ROS, and higher
molecular weight toxins. Using PIF for optimizing in vitro fertilization embryos
development and reducing RPL is warranted.
PMID- 28423692
TI - The relationship between members of the canonical NF-kappaB pathway, components
of tumour microenvironment and survival in patients with invasive ductal breast
cancer.
AB - The aim of the present study was to examine the relationship between tumour NF
kappaB activation, tumour microenvironment including local inflammatory response
(LIR) and cancer-specific survival in patients with operable ductal breast
cancer.Immunohistochemistry (tissue microarray of 376 patients) and western
blotting (MCF7 and MDA-MB-231 breast cancer cells) was performed to assess
expression of key members of the canonical NF-kappaB pathway (inhibitory kappa B
kinase (IKKbeta) and phosphorylated p65 Ser-536 (p-p65)). Following silencing of
IKKbeta, cell viability and apoptosis was assessed in both MCF7 and MDA-MB-231
cell lines.P-p65 was associated with cancer-specific survival (CSS) (nuclear
P=0.042 and total P=0.025). High total p-p65 was associated with increase grade
tumour grade (P=0.010), ER positivity (P=0.023), molecular subtype (P=0.005),
lower Klintrup-Makinen grade (P=0.013) and decreased CD138 count (P=0.032). On
multivariate analysis, total p-p65 expression independently associated with
poorer CSS (P=0.020). In vitro work demonstrated that the canonical NF-kappaB
pathway was inducible by exposure to TNFalpha in ER-positive MCF7 cells and to a
lesser extent in ER-negative MDA-MB-231 cells. Reduction of IKKbeta expression by
siRNA transfection increased levels of apoptosis and reduced cell viability in
both MCF7 (P=<0.001, P=<0.001, respectively) and MDA-MB-231 cells (P=>0.001,
P=0.002, respectively). This is consistent with the hypothesis that canonical
IKKbeta-NF-kappaB signalling drives tumour survival.These results suggest that
activation of the canonical NF-kappaB pathway is an important determinant of poor
outcome in patients with invasive ductal breast cancer.
PMID- 28423693
TI - Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to
BAFF in treating human papillomavirus-associated cancer.
AB - B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that
not only stimulates B and T cells but also counteracts immune tolerance. BAFF is
also a type II membrane protein, which is secreted through the endoplasmic
reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance
the presentation of major histocompatibility complex class I molecules. These
characteristics represent an opportunity to enhance the antitumor effects of DNA
vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA
vaccine and evaluated its antitumor effects. We found that this vaccine increased
E7-specific CD8+ T-cell immune responses, engendered major antitumor effects
against E7-expressing tumors, and prolonged the survival of the immunized mice.
Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed
considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do
not contribute to this immune response. Image analysis through confocal
fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to
the ER, but not BAFF lacking 128 N-terminal residues that generated a lower
number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated
that the ER-targeting characteristic of BAFF is the main factor improving the
potency of DNA vaccines.
PMID- 28423694
TI - Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor
prognosis of head and neck carcinomas.
AB - BACKGROUND: Epstein-Barr virus (EBV) is the main cause of nasopharyngeal
carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its
role remains controversial. RESULTS: EBV was found in 80% and 21% of the samples
with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples
were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse
prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections
associated with a shorter survival. LMP-1 expression, positive in 51% of samples
did not correlate with the disease outcome. MATERIALS AND METHODS: We analyzed
EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ
hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts
(EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based
method. The results were correlated with HPV-status and disease outcome.
CONCLUSIONS: EBV is transcriptionally active in NPC cells but also in a subgroup
of other HNSCCs.
PMID- 28423695
TI - NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the
mitochondria in breast cancer.
AB - Chemo-resistance presents a difficult challenge for the treatment of breast
cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2)
is involved in p53-mediated apoptosis induced by chemotherapy, through a
mechanism that has so far remained obscure. Here, we explored the role of NDRG2
in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2
expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2
can promote ADR sensitivity by inhibiting proliferation, enhancing cellular
damage responses, and promoting apoptosis in a p53-dependent manner. We also
found that NDRG2 could upregulate Bad expression by increasing its half-life,
which is associated with p53 to mitochondria. Hence, our collective data provided
the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent
on p53 by preventing p53 from entering the nucleus rather than changing its
expression.
PMID- 28423696
TI - Improvement of dexamethasone sensitivity by chelation of intracellular Ca2+ in
pediatric acute lymphoblastic leukemia cells through the prosurvival kinase
ERK1/2 deactivation.
AB - Previous studies have demonstrated that glucocorticoid hormones, including
dexamethasone, induced alterations in intracellular calcium homeostasis in acute
lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular
calcium homeostasis participates in dexamethasone sensitivity and resistance on
ALL cells remains elusive. Here, we found that treatment of cells with
dexamethasone resulted in increased intracellular calcium concentrations through
store-operated calcium entry stimulation, which was curtailed by store-operated
calcium channel blockers. We show that BAPTA-AM, an intracellular Ca2+ chelator,
synergistically enhances dexamethasone lethality in two human ALL cell lines and
in three primary specimens. This effect correlated with the inhibition of the
prosurvival kinase ERK1/2 signaling pathway. Chelating intracellular calcium with
Bapta-AM or inhibiting ERK1/2 with PD98059 significantly potentiated
dexamethasone-induced mitochondrial membrane potential collapse, reactive oxygen
species production, cytochrome c release, caspase-3 activity, and cell death.
Moreover, we show that thapsigargin elevates intracellular free calcium ion
level, and activates ERK1/2 signaling, resulting in the inhibition of
dexamethasone-induced ALL cells apoptosis. Together, these results indicate that
calcium-related ERK1/2 signaling pathway contributes to protect cells from
dexamethasone sensitivity by limiting mitochondrial apoptotic pathway. This
report provides a novel resistance pathway underlying the regulatory effect of
dexamethasone on ALL cells.
PMID- 28423697
TI - Essential role of endogenous prolactin and CDK7 in estrogen-induced upregulation
of the prolactin receptor in breast cancer cells.
AB - Our early studies have shown that Estradiol (E2)/Estrogen Receptor alpha (ER) in
a non-DNA dependent manner through complex formation with C/EBPbeta/SP1 induced
transcriptional activation of the generic hPIII promoter and expression of the
Prolactin Receptor (PRLR) receptor in MCF-7 cells. Subsequent studies
demonstrated effects of unliganded ERalpha with requisite participation of
endogenous PRL on the activation of PRLR transcription. Also, EGF/ERBB1 in the
absence of PRL and E2 effectively induced upregulation of the PRLR. In this study
we have delineated the transcriptional mechanism of upregulation of PRLR receptor
induced by E2 incorporating knowledge of the various transcriptional upregulation
modalities from our previous studies. Here, we demonstrate an essential
requirement of STAT5a induced by PRL via PRLR receptor which associates at the
promoter and its interaction with phoshoERalpha S118. Knock-down of PRL by siRNA
significantly reduced E2-induced PRLR promoter activity, mRNA and protein
expression, recruitment of ERalpha to the complex at promoter, C/EBPbeta
association to its DNA site and productive complex formation at hPIII promoter.
The specific CDK7 inhibitor (THZ1) that attenuates E2-induced ERalpha
phosphorylation at S118 abrogated E2-induced PRLR promoter activation. Further
studies demonstrated that E2 induced cell migration was inhibited by PRL siRNA
and THZ1 indicating its dependence on PRL/PRLR and CDK7, respectively. Our
studies have demonstrated the essential role of endogenous PRL and CDK7 in the
upregulation of PRLR by E2 and provide insights for therapeutic approaches that
will mitigate the transcription/expression of PRLR and its participation in
breast cancer progression fueled by E2 and PRL via their cognate receptors.
PMID- 28423698
TI - Parameters of simultaneous 18F-FDG-PET/MRI predict tumor stage and several
histopathological features in uterine cervical cancer.
AB - The purpose of this study was to analyze associations between apparent diffusion
coefficient (ADC) and standardized uptake values (SUV) values and different
histopathological parameters in uterine cervical cancer. 21 patients with primary
uterine cervical cancer were involved into the study. All patients underwent a
whole body simultaneous18F-FDG PET/MRI. Mean and maximum SUV were noted (SUVmean
and SUVmax). In all tumors minimal, mean, and maximal ADC values (ADCmin,
ADCmean, and ADCmax) were estimated. Combined parameters were calculated:
SUVmax/SUVmean, ADCmin/ ADCmean, SUVmax/ADCmin and SUVmax/ADCmean. In all cases
the diagnosis was confirmed histopathologically by tumor biopsy. Histological
slices were stained by hematoxilin and eosin, MIB 1 monoclonal antibody, and p16.
All histopathological images were digitalized and analyzed by using a ImageJ
software 1.48v. The following parameters were estimated: cell count,
proliferation index KI 67, total and average nucleic areas, epithelial and
stromal areas. Spearman's correlation coefficient was used to analyze
associations between ADC and SUV values and histological parameters. P values <=
0.05 were considered as statistically significant. ADCmin and ADCmin/ ADCmean
were statistically significant lower in N positive tumors. KI 67 correlated
statistically significant with SUVmax (r = 0.59, p = 0.005), SUVmean (0.45, p =
0.04), ADCmin (r = -0.48, p = 0.03), SUVmax/ADCmin (r = 0.71, p = 0.001),
SUVmax/ADCmean (0.75, p = 0.001). SUVmax correlated well with epithelial area (r
= 0.71, p = 0.001) and stromal areas (r = -0.71, p = 0.001). SUV values, ADCmin,
SUVmax/ADCmin and SUVmax/ADCmean correlated statistically significant with KI 67
and can be used to estimate the proliferation potential of tumors. SUV values
correlated strong with epithelial area of tumor reflected metabolic active areas.
PMID- 28423699
TI - Long non-coding RNA LUCAT1 is associated with poor prognosis in human non-small
lung cancer and regulates cell proliferation via epigenetically repressing p21
and p57 expression.
AB - Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key
roles in regulating cellular processes, such as proliferation, invasion, and
metastasis. These lncRNAs have been shown to be abnormally expressed in
tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non
small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the
expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to
non-tumor tissues, and its expression was associated with tumor size, tumor-node
metastasis (TNM) stage and overall survival (OS). Further experiments showed that
LUCAT1 knockdown inhibited cell proliferation both in vitro and in vivo.
Mechanistic investigations showed that LUCAT1 plays a key role in G0/G1 arrest.
We further demonstrated that LUCAT1 was associated with polycomb repressor
complexes (PRC2) and that this association was required for epigenetically
repression of p21 and p57, thus contributing to the regulation of NSCLC cell
cycle and proliferation. In summary, our results show that LUCAT1 could regulate
tumorigenesis of NSCLC and be biomarker for poor prognosis in NSCLC.
PMID- 28423700
TI - HLA class I loss in metachronous metastases prevents continuous T cell
recognition of mutated neoantigens in a human melanoma model.
AB - T lymphocytes against tumor-specific mutated neoantigens can induce tumor
regression. Also, the size of the immunogenic cancer mutanome is supposed to
correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied
the susceptibility of tumor cell lines from lymph node metastases occurring in a
melanoma patient over several years towards blood-derived, neoantigen-specific
CD8+ T cells. In contrast to a cell line established during early stage III
disease, all cell lines generated at later time points from stage IV metastases
exhibited partial or complete loss of HLA class I expression. Whole exome and
transcriptome sequencing of the four tumor lines and a germline control were
applied to identify expressed somatic single nucleotide substitutions (SNS),
insertions and deletions (indels). Candidate peptides encoded by these variants
and predicted to bind to the patient's HLA class I alleles were synthesized and
tested for recognition by autologous mixed lymphocyte-tumor cell cultures
(MLTCs). Peptides from four mutated proteins, HERPUD1G161S, INSIG1S238F,
MMS22LS437F and PRDM10S1050F, were recognized by MLTC responders and MLTC-derived
T cell clones restricted by HLA-A*24:02 or HLA-B*15:01. Intracellular peptide
processing was verified with transfectants. All four neoantigens could only be
targeted on the cell line generated during early stage III disease. HLA loss
variants of any kind were uniformly resistant. These findings corroborate that,
although neoantigens represent attractive therapeutic targets, they also
contribute to the process of cancer immunoediting as a serious limitation to
specific T cell immunotherapy.
PMID- 28423701
TI - Identification of protein clusters predictive of tumor response in rectal cancer
patients receiving neoadjuvant chemo-radiotherapy.
AB - Preoperative neoadjuvant chemoradiotherapy (nCRT) is the gold standard in locally
advanced rectal cancer, only 10-30% of patients achieving benefits. Currently,
there is a need of a reliable selection of markers for the identification of poor
or non-responders prior to therapy. In this work, we compared protein profiles
before therapy of patients differing in their responses to nCRT to find novel
predictive markers of response to therapy. Patients were grouped into 3 groups
according to their tumor regression grading (TRG) after surgery: 'TRG 1-2', good
responders, 'TRG 3' and 'TRG 4', poor responders. Paired surgical specimens of
rectal cancer and healthy (histologically confirmed) rectal tissues from 15
patients were analysed before nCRT by two dimensional difference in gel
electrophoresis followed by mass spectrometry. Thirty spots were found as
differentially expressed (p < 0.05). Among them, 3 spots (spots 471, 683 and 684)
showed an increased amount of protein in poor responders compared with good
responders, and they were more tumor associated compared with healthy tissues.
Proteins of these spots were identified as fibrinogen beta chain fragment D,
actin isoforms, B9 and B5 serpins, cathepsin D isoforms and peroxiredoxin-4. In
an independent validation set of 20 rectal carcinomas we validated the increased
fibrinogen beta chain abundance before nCRT in poor responders by immunoblotting.
In conclusion, we propose a risk-stratification tool in predicting the response
to nCRT treatment in rectal cancer based on the quantity of these proteins.
PMID- 28423702
TI - Experience with precision genomics and tumor board, indicates frequent target
identification, but barriers to delivery.
AB - BACKGROUND: The ability to analyze the genomics of malignancies has opened up new
possibilities for off-label targeted therapy in cancers that are refractory to
standard therapy. At Mayo Clinic these efforts are organized through the Center
for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed
and integrated by a team of bioinformaticians and cancer biologists.
Therapeutically actionable mutations were identified in 65% (92/141) of the
patients tested with 32% (29/92) receiving genomically targeted therapy with FDA
approved drugs or in an independent clinical trial with 45% (13/29) responding.
Standard of care (SOC) options were continued by 15% (14/92) of patients tested
before exhausting SOC options, with 71% (10/14) responding to treatment. Over 35%
(34/92) of patients with actionable targets were not treated with 65% (22/34)
choosing comfort measures or passing away. MATERIALS AND METHODS: Patients (N =
165) were referred to the CIM Clinic between October 2012 and December 2015. All
patients received clinical genomic panel testing with selected subsets receiving
array comparative genomic hybridization and clinical whole exome sequencing to
complement and validate panel findings. A genomic tumor board (GTB) reviewed
results and, when possible, developed treatment recommendations. CONCLUSIONS:
Treatment decisions driven by tumor genomic analysis can lead to significant
clinical benefit in a minority of patients. The success of genomically driven
therapy depends both on access to drugs and robustness of bioinformatics
analysis. While novel clinical trial designs are increasing the utility of
genomic testing, robust data sharing of outcomes is needed to optimize clinical
benefit for all patients.
PMID- 28423703
TI - Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent
apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer
cells.
AB - Artocarpin has been shown to exhibit cytotoxic effects on different cancer cells,
including non-small cell lung carcinoma (NSCLC, A549). However, the underlying
mechanisms remain unclear. Here, we explore both p53-dependent and independent
apoptosis pathways in artocarpin-treated NSCLC cells. Our results showed that
artocarpin rapidly induced activation of cellular protein kinases including
Erk1/2, p38 and AktS473. Inhibition of these protein kinases prevented artocarpin
induced cell death. Moreover, artocarpin-induced phosphorylation of these protein
kinases and apoptosis were mediated by induction of reactive oxygen species
(ROS), as pretreatment with NAC (a ROS scavenger) and Apocynin (a Nox-2
inhibitor) blocked these events. Similarly, transient transfection of p47Phox or
p91Phox siRNA attenuated artocarpin-induced NADPH oxidase activity and cell
death. In addition, p53 dependent apoptotic proteins including PUMA, cytochrome
c, Apaf-1 and caspase 3 were activated by artocarpin, and these effects can be
abolished by antioxidants, MAPK inhibitors (U0126 and SB202190), but not by PI3K
inhibitor (LY294002). Furthermore, we found that artocarpin-induced Akt
phosphorylation led to increased NF-kappaB activity, which may act as an upstream
regulator in the c-Myc and Noxa pathway. Therefore, we propose that enhancement
of both ERK/ p38/ p53-dependent or independent AktS473/NF-kappaB/c-Myc/Noxa
cascade by Nox-derived ROS generation plays an important role in artocarpin
induced apoptosis in NSCLC cells.
PMID- 28423704
TI - Prognostic and clinicopathological role of long non-coding RNA UCA1 in various
carcinomas.
AB - Urothelial cancer associated 1 (UCA1) as an oncogenic long non-coding RNA
(LncRNA) was aberrantly upregulated in various solid tumors. Numerous studies
have demonstrated overexpression of UCA1 is an unfavorable prognostic indicator
in cancer patients. This study aimed to further explore the prognosis role and
clinical significance of UCA1 in cancer. Eligible studies were recruited by a
systematic search in PubMed, Embase, Cochrane Library and Web of Science
databases. A total of 19/16 studies with 1587/1291 cancer patients were included
to evaluate the association between UCA1 expression and overall survival (OS) and
clinicopathological factors of malignancies by computing hazard ratio (HR), odds
ratios (OR) and confidence interval (CI). The meta-analysis indicated
overexpression of UCA1 was significantly correlated with unexpected OS in
patients with cancer (pooled HR = 1.85, 95% CI 1.62-2.10, p < 0.001). There was
also a significantly negative association between high level of UCA1 and poor
grade cancer (pooled OR = 2.74, 95% CI 2.04-3.70, p < 0.001) and positive
lymphatic metastasis (pooled OR = 2.43, 95% CI 1.72-3.41, p < 0.001). In
conclusion, our study suggested that UCA1 was correlated with more advanced
clinicopathological features and poor prognosis as a novel predictive biomarker
of patients with various tumors.
PMID- 28423706
TI - Identification of Ras suppressor-1 (RSU-1) as a potential breast cancer
metastasis biomarker using a three-dimensional in vitro approach.
AB - Breast cancer (BC) is the most common malignant disease in women, with most
patients dying from metastasis to distant organs, making discovery of novel
metastasis biomarkers and therapeutic targets imperative. Extracellular matrix
(ECM)-related adhesion proteins as well as tumor matrix stiffness are important
determinants for metastasis. As traditional two-dimensional culture does not take
into account ECM stiffness, we employed 3-dimensional collagen I gels of
increasing concentration and stiffness to embed BC cells of different
invasiveness (MCF-7, MDA-MB-231 and MDA-MB-231-LM2) or tumor spheroids. We tested
the expression of cell-ECM adhesion proteins and found that Ras Suppressor-1 (RSU
1) is significantly upregulated in increased stiffness conditions. Interestingly,
RSU-1 siRNA-mediated silencing inhibited Urokinase Plasminogen Activator, and
metalloproteinase-13, whereas tumor spheroids formed from RSU-1-depleted cells
lost their invasive capacity in all cell lines and stiffness conditions. Kaplan
Meier survival plot analysis corroborated our findings showing that high RSU-1
expression is associated with poor prognosis for distant metastasis-free and
remission-free survival in BC patients. Taken together, our results indicate the
important role of RSU-1 in BC metastasis and set the foundations for its
validation as potential BC metastasis marker.
PMID- 28423707
TI - Tropomyosin-related kinase B mediated signaling contributes to the induction of
malignant phenotype of gallbladder cancer.
AB - This study aims to demonstrate the clinical and biological significance of Brain
derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) signaling
in gallbladder cancer (GBC) through a series of in vitro and in vivo experiments.
TrkB expression was detected in 63 (91.3%) out of 69 surgically resected primary
GBC specimens by immunohistochemistry. TrkB expression in the invasive front
correlated with T factor (p=0.0391) and clinical staging (p=0.0391). Overall
survival was lower in patients with high TrkB expression in the invasive front
than in those with low TrkB expression (p=0.0363). In vitro experiment, we used
five TrkB-expressing GBC cell lines with or without K-ras mutation. TrkB-mediated
signaling increased proliferation and the invasiveness by inducing epithelial
mesenchymal transition, and activating matrix metalloproteinases-2 (MMP-2) and
MMP-9. Inhibition of TrkB-mediated signaling also decreased hypoxia-inducible
factor-1alpha, vascular endothelial growth factor A (VEGF-A), VEGF-C, and VEGF-D
expression. In vivo experiment, inhibition of TrkB-mediated signaling suppressed
tumorigenicity and tumor growth in GBC. These findings demonstrate that TrkB
mediated signaling contributes to the induction of malignant phenotypes
(proliferation, invasiveness, angiogenesis, lymphangiogenesis, and tumorigenesis)
in GBC, and could be a promising therapeutic target regardless of K-ras mutation
status.
PMID- 28423709
TI - Prognostic values of clinicopathological characteristics and survival outcomes in
prostate infiltrating ductal carcinoma: a population-based study.
AB - Infiltrating ductal carcinoma (IDC) is a rare histologic subtype of prostate
cancer. We investigated the clinicopathological features and prognosis of IDC
compared with acinar cell carcinoma (ACC). We identified 3814 men diagnosed with
prostate cancer between 2004 to and 2013 in the Surveillance, Epidemiology, and
End Results database, including 511 IDC and 3303 ACC cases. Prostate cancer
specific survival (PCSS) was compared using univariate and multivariate Cox
proportional hazards models. Generally, IDC occurred in older men (>= 65 years
old) and presented with larger sizes, and higher grades, American Joint Committee
on Cancer (AJCC) stages, AJCC T stages, lymph node positive rates and metastasis
rates. Men with IDC were less likely to undergo radical prostatectomy, but more
likely to be treated with adjuvant radiation than men with ACC. Five-year PCSS
rates were significantly worse in IDC. In the multivariate analysis, patients
with ACC had a better PCSS than patients with IDC. In conclusion, IDC has unique
clinicopathological characteristics and has worse prognosis than ACC.
Multivariable Cox regression analysis showed that age over 85 years, higher grade
and T stage, and metastasis at diagnosis were independent prognostic factors of
worse survival outcomes, whereas radical prostatectomy was an independent
prognostic factor of better survival outcomes.
PMID- 28423708
TI - Targeting the centriolar replication factor STIL synergizes with DNA damaging
agents for treatment of ovarian cancer.
AB - Advanced ovarian cancer is an incurable disease. Thus, novel therapies are
required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA
screen performed in 42 ovarian cancer cell lines identified the centriolar
replication factor STIL as an essential gene for ovarian cancer cells. This was
verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion
by administration of siRNA in neutral liposomes resulted in robust anti-tumor
effect that was further enhanced in combination with cisplatin. Consistent with
this finding, STIL depletion enhanced the extent of DNA double strand breaks
caused by DNA damaging agents. This was associated with centrosomal depletion,
ongoing genomic instability and enhanced formation of micronuclei. Interestingly,
the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we
observed that depletion of STIL enhanced canonical homologous recombination
repair and increased BRCA1 and RAD51 foci in response to DNA double strand
breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA
damaging chemotherapeutic drugs in treatment of ovarian cancer.
PMID- 28423710
TI - Phospholipase Cdelta1 suppresses cell migration and invasion of breast cancer
cells by modulating KIF3A-mediated ERK1/2/beta- catenin/MMP7 signalling.
AB - Phospholipase C delta1 (PLCD1) encodes an enzyme involved in energy metabolism,
calcium homeostasis and intracellular movement. It is located at 3p22 in a region
that is frequently deleted in multiple cancers, and the PLCD1 enzyme is a
potential tumour suppressor in breast cancer that inhibits matrix metalloprotease
(MMP) 7, but the detailed mechanism remains elusive. In this study, we found that
PLCD1 was downregulated in breast cancers, and the gain-or-loss functional assay
revealed that PLCD1 inhibited cell migration and invasion in vitro via the
ERK1/2/beta-catenin/MMP7 signalling pathway. Furthermore, KIF3A was identified as
a downstream mediator of PLCD1, and there was an inverse correlation between the
expression of PLCD1 and KIF3A. Knockdown of KIF3A expression alone suppressed
cell migration and invasion, and attenuated ERK1/2/beta-catenin/MMP7 signalling
that was reactivated by knocking down PLCD1 in vitro. Collectively, our findings
suggest that PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of
ERK1/2/beta-catenin/MMP7 signalling, at least in part, in breast cancer.
PMID- 28423711
TI - The antitumor activity and preliminary modeling on the potential mechanism of
action of human peroxiredoxin-5.
AB - Goat peroxiredoxin-5 (gPRDX5) was verified as a good anti-cancer bioactive
peptide (ACBP) against different tumor cell lines. Considering the immunogenicity
between species for further therapeutic application, it is necessary to similarly
investigate the antitumor activity of human peroxiredoxin-5 (hPRDX5) with 89%
similarity in sequence to gPRDX5. In order to evaluate its antitumor activity,
the potential anti-neoplastic effect of hPRDX5 on a mouse model was observed
directly. The results of its in vivo antitumor activity suggested that hPRDX5
could resist immunosuppression by promoting lymphocyte proliferation and up
regulating the levels of serum cytokines. Meanwhile, PD-L1 was speculated as one
of the targets of hPRDX5 to inhibit tumor by enhancing the immune activity
according to a preliminary molecular docking study on the interactions between
hPRDX5 and PD-L1. The modeling provides a basis for structural modification on
hPRDX5/PD-L1 for further biological and biochemical study on the pathway blocking
mechanism of hPRDX5. In this work, the results demonstrate that hPRDX5 displays
efficient antitumor and immunoregulatory properties in the colon cancer
C26/BALB/c and melanoma B16/C57Bl/6 mice tumor models, and suggest the potential
of developing peptides from hPRDX5 as low molecular weight drug candidates for
corresponding cancer immunotherapy.
PMID- 28423712
TI - Model-based unsupervised learning informs metformin-induced cell-migration
inhibition through an AMPK-independent mechanism in breast cancer.
AB - We demonstrate that model-based unsupervised learning can uniquely discriminate
single-cell subpopulations by their gene expression distributions, which in turn
allow us to identify specific genes for focused functional studies. This method
was applied to MDA-MB-231 breast cancer cells treated with the antidiabetic drug
metformin, which is being repurposed for treatment of triple-negative breast
cancer. Unsupervised learning identified a cluster of metformin-treated cells
characterized by a significant suppression of 230 genes (p-value < 2E-16). This
analysis corroborates known studies of metformin action: a) pathway analysis
indicated known mechanisms related to metformin action, including the citric acid
(TCA) cycle, oxidative phosphorylation, and mitochondrial dysfunction (p-value <
1E-9); b) 70% of these 230 genes were functionally implicated in metformin
response; c) among remaining lesser functionally-studied genes for metformin
response was CDC42, down-regulated in breast cancer treated with metformin.
However, CDC42's mechanisms in metformin response remained unclear. Our
functional studies showed that CDC42 was involved in metformin-induced inhibition
of cell proliferation and cell migration mediated through an AMPK-independent
mechanism. Our results points to 230 genes that might serve as metformin response
signatures, which needs to be tested in patients treated with metformin and,
further investigation of CDC42 and AMPK-independence's role in metformin's
anticancer mechanisms.
PMID- 28423713
TI - Systematic analysis of gene expression alterations and clinical outcomes of
adenylate cyclase-associated protein in cancer.
AB - Adenylate Cyclase-associated protein (CAP) is an evolutionarily conserved protein
that regulates actin dynamics. Our previous study indicates that CAP1 is
overexpressed in NSCLC tissues and correlated with poor clinical outcomes, but
CAP1 in HeLa cells actually inhibited migration and invasion, the role of CAP was
discrepancy in different cancer types. The present study aims to determine
whether CAP can serve as a prognostic marker in human cancers. The CAP expression
was assessed using Oncomine database to determine the gene alteration during
carcinogenesis, the copy number alteration, or mutations of CAP using cBioPortal,
International Cancer Genome Consortium, and Tumorscape database investigated, and
the association between CAP expression and the survival of cancer patient using
Kaplan-Meier plotter and PrognoScan database evaluated. Therefore, the functional
correlation between CAP expression and cancer phenotypes can be established;
wherein CAP might serve as a diagnostic marker or therapeutic target for certain
types of cancers.
PMID- 28423714
TI - Usefulness of the MRP2 promoter to overcome the chemoresistance of
gastrointestinal and liver tumors by enhancing the expression of the drug
transporter OATP1B1.
AB - Tumor response to chemotherapy is often limited by drug export through ABC
proteins. To overcome this problem, here we have investigated the usefulness of
inducing the expression of the multidrug uptake transporter OATP1B1 under the
control of the MRP2 promoter (MRP2pr). Human hepatoma cells (Alexander) were
transfected with MRP2pr fragments of different length fused to the firefly
luciferase ORF in order to select the shortest fragment with the highest response
to dexamethasone, which was subsequently used to generate the chimeric construct
MRP2pr-OATP1B1-V5. Hepatoma cells transduced with MRP2pr-OATP1B1-V5 resulted in
dexamethasone-sensitive inducible OATP1B1 expression and enhanced selective
antitumor response to OATP1B1 substrates (paclitaxel, Bamet-R2 and Bamet-UD2). In
human colon cancer cells LS174T/R, used as a model of endogenous chemoresistance
due to MRP2 overexpression, MRP2pr-OATP1B1 induced OATP1B1 expression together
with chemosensitivity to OATP1B1 substrates. In nude mice, xenografted tumors
formed by LS174T/R cells transduced with MRP2pr-OATP1B1 plus treatment with
dexamethasone were markedly sensitized to Bamet-UD2. In conclusion, the induced
expression of anticancer drug uptake transporters, under the control of promoters
of ABC proteins involved in chemoresistance, constitutes an interesting approach
to overcome the poor response of cancer to chemotherapy due to reduced drug
uptake and/or enhanced drug export.
PMID- 28423715
TI - A functional variant at the miRNA binding site in HMGB1 gene is associated with
risk of oral squamous cell carcinoma.
AB - Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally
associated with both hereditary and acquired factors. The high mobility group box
1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain
nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide
range of pathological processes, including inflammation and cancer. The present
study explores the impact of HMGB1 gene polymorphisms, combined with
environmental risks regarding susceptibility to oral tumorigenesis. Four single
nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825,
rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772
patients with OSCC. We found an association between the wild-type allele of
rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and
AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics
analysis was used to characterize the functional relevance of these variants for
the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3'-UTR
and promoter regions. Moreover, in considering behavioral exposure to
environmental carcinogens, the presence of the four HMGB1 SNPs, combined
with/without betel quid chewing and smoking showed, profoundly synergistic
effects on the risk of OSCC. In conclusion, we present a potential clinical
relevance for HMGB1 variants in OSCC, as well as associations between HMGB1
polymorphisms, haplotypes and environmental risk factors. The finding may help in
development of optimal therapeutic approaches for OSCC patients.
PMID- 28423716
TI - Oncogenic features of neuromedin U in breast cancer are associated with NMUR2
expression involving crosstalk with members of the WNT signaling pathway.
AB - Neuromedin U (NMU) has been shown driving the progression of various tumor
entities, including breast cancer. However, the expression pattern of NMU and its
receptors in breast cancer tissues as well as systematic insight into mechanisms
and downstream targets of the NMU-driven signaling pathways are still elusive.
Here, NMU expression was found up-regulated in all breast cancer subtypes when
compared to healthy breast tissue. Using an in silico dataset comprising 1,195
samples, high NMU expression was identified as an indicator of poor outcome in
breast tumors showing strong NMUR2 expression. Next, the biological impact of NMU
on breast cancer cells in relation to NMUR2 expression was analyzed. Ectopic NMU
expression reduced colony growth while promoting a motile phenotype in NMUR2
positive SKBR3 but not NMUR2-negative Hs578T cells. To uncover signaling pathways
and key molecules affected by NMU in SKBR3 cells, Affymetrix microarray analysis
was applied. Forced NMU expression affected molecules involved in WNT receptor
signaling among others. As such we demonstrated enhanced activation of the
WNT/planar cell polarity (PCP) effector RAC1 and down-regulation of canonical WNT
targets such as MYC. In summary, NMU might contribute to progression of NMUR2
positive breast cancer representing a potential druggable target for future
personalized strategies.
PMID- 28423717
TI - Non-homologous end joining induced alterations in DNA methylation: A source of
permanent epigenetic change.
AB - In addition to genetic mutations, epigenetic revision plays a major role in the
development and progression of cancer; specifically, inappropriate DNA
methylation or demethylation of CpG residues may alter the expression of genes
that promote tumorigenesis. We hypothesize that DNA repair, specifically the
repair of DNA double strand breaks (DSB) by Non-Homologous End Joining (NHEJ) may
play a role in this process. Using a GFP reporter system inserted into the genome
of HeLa cells, we are able to induce targeted DNA damage that enables the cells,
after successfully undergoing NHEJ repair, to express WT GFP. These GFP+ cells
were segregated into two expression classes, one with robust expression (Bright)
and the other with reduced expression (Dim). Using a DNA hypomethylating drug
(AzadC) we demonstrated that the different GFP expression levels was due to
differential methylation statuses of CpGs in regions on either side of the break
site. Deep sequencing analysis of this area in sorted Bright and Dim populations
revealed a collection of different epi-alleles that display patterns of DNA
methylation following repair by NHEJ. These patterns differ between Bright and
Dim cells which are hypo- and hypermethylated, respectively, and between the post
repair populations and the original, uncut cells. These data suggest that NHEJ
repair facilitates a rewrite of the methylation landscape in repaired genes,
elucidating a potential source for the altered methylation patterns seen in
cancer cells, and understanding the mechanism by which this occurs could provide
new therapeutic targets for preventing this process from contributing to
tumorigenesis.
PMID- 28423718
TI - iTRAQ-based quantitative proteomic analysis of Yamanaka factors reprogrammed
breast cancer cells.
AB - Cancer cells had been developed to be reprogrammed into embryonic stem like cells
by induced pluripotent stem cells (iPSCs) technology, however, the tumor
differentiation/dedifferentiation mechanisms had not yet been analyzed on a
genome-wide scale. Here, we inserted the four stem cell transcription factor
genes OCT4, SOX2, C-MYC and KLF4 into MCF cells (MCFs), represented a female
breast cancer cell type, and obtained iPSCs (Mcfips) in about 3 weeks. By using
the LC MS/MS iTRAQ technology, we analyzed the proteomic changes between MCFs and
Mcfips. Of identified 4,616 proteins totally, 247 and 142 differentially
expressed (DE) proteins were found in Mcfips compared with human induce
pluripotent stem cells (Hips) and MCFs, respectively. 35 co-up and 10 co-down
regulated proteins were recognized in DE proteins. Above DE proteins were
categorized with GO functional classification annotation and KEGG metabolic
pathway analysis into biological processes. In the protein interaction network,
we found 37 and 39 hubs interacted with more than one protein in Mcfips comparing
to Hips, in addition, 25 and 9 hubs were identified in Mcfips comparing to MCFs.
Importantly, the mitochondria, ribosome and tumor suppressor proteins were found
to be core regulators of tumor reprogramming, which might contribute to
understand the mechanisms in relation to the occurrences and progression of a
tumor. Thus, our study provided a valuable data for exploring the possibility to
normalize the malignant phenotype.
PMID- 28423719
TI - AMPKalpha phosphatase Ppm1E upregulation in human gastric cancer is required for
cell proliferation.
AB - Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer
strategy. In the current study, we tested expression and potential function of
Ca2+/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKalpha
phosphatase, in human gastric cancers. Ppm1E expression was elevated in human
gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p
AMPKalpha, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation.
Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in
human gastric cancer cell lines (AGS, HGC-27, and SNU601). Intriguingly, Ppm1E
knockdown by shRNA induced AMPK activation, mTORC1 inactivation, and
proliferation inhibition in AGS cells. On the other hand, forced over-expression
of Ppm1E induced further AMPK inhibition and mTORC1 activation to enhance AGS
cell proliferation. Remarkably, microRNA-135b-5p ("miR-135b-5p"), an anti-Ppm1E
microRNA, was downregulated in both human gastric cancer tissues and cells.
Reversely, miR-135b-5p exogenous expression caused Ppm1E depletion, AMPK
activation, and AGC cell proliferation inhibition. Together, Ppm1E upregulation
in human gastric cancer is important for cell proliferation, possible via
regulating AMPK-mTOR signaling.
PMID- 28423720
TI - Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant
chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer.
AB - A meta-analysis was conducted to compare oxaliplatin-based with fluorouracil
based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally
advanced rectal cancer. MEDLINE, EMBASE and CENTRAL were systematically searched
for relevant randomized controlled trials (RCTs) until January 31 2017. Review
Manager (version 5.3) was used to analyze the data. Dichotomous data were
calculated by odds ratio (OR) with 95% confidence intervals (CI). A total of 8
RCTs with 6103 stage II or III rectal cancer patients were analyzed, including
2887 patients with oxaliplatin+fluorouracil regimen and 3216 patients with
fluorouracil alone regimen. Compared with fluorouracil-based regimen group,
oxaliplatin-based regimen group attained higher pathologic complete response (OR
= 1.29, 95% CI: 1.12-1.49, P = 0.0005) and 3-year disease-free survival (OR =
1.15, 95% CI: 0.93-1.42, P = 0.21), but suffered greater toxicity (OR = 2.07, 95%
CI: 1.52-2.83, P < 0.00001). Also, there were no significant differences between
two regimens in sphincter-sparing surgery rates (OR = 0.94, 95% CI: 0.83-1.06, P
= 0.33), 5-year disease-free survival (OR = 1.15, 95% CI: 0.93-1.42, P = 0.21)
and overall survival (3-year, OR = 1.14, 95% CI: 0.98-1.34, P = 0.09; 5-year, OR
= 1.06, 95% CI: 0.78-1.44, P = 0.70). In conclusion, the benefits of adding
oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant
chemotherapy for locally advanced rectal cancer remains controversial, and cannot
be considered a standard approach.
PMID- 28423721
TI - Downregulation of phosphorylated MKK4 is associated with a poor prognosis in
colorectal cancer patients.
AB - Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N
terminal kinase signaling and influences malignant metastasis. Here, we used
immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine
their association with the clinicopathological features of a pilot set of patient
samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and
colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation
set of CRC cases with accompanying follow-up data to confirm their
clinicopathological and prognostic significance. pMKK4 levels, which were high in
79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC
samples. pMKK4 downregulation was associated with metastasis, especially to the
liver. In the validation set, pMKK4 downregulation was associated with increases
in invasive depth, lymph node metastasis, distant metastasis, and TNM stage.
Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM
stage were correlated with disease-free survival and overall survival.
Multivariate analysis indicated that decreased pMKK4 expression was an
independent risk factor for disease-free survival in CRC patients. These results
suggest that CRC patients with low pMKK4 immunochemistry scores should be
monitored carefully for early detection of possible recurrences, especially liver
metastasis.
PMID- 28423722
TI - The importance of the genomic landscape in Waldenstrom's Macroglobulinemia for
targeted therapeutical interventions.
AB - The Literature has recently reported on the importance of genomics in the field
of hematologic malignancies, including B-cell lymphoproliferative disorders such
as Waldenstrom's Macrolgobulinemia (WM). Particularly, whole exome sequencing has
led to the identification of the MYD88L265P and CXCR4C1013G somatic variants in
WM, occurring in about 90% and 30% of the patients, respectively. Subsequently,
functional studies have demonstrated their functional role in supporting WM
pathogenesis and disease progression, both in vitro and in vivo, thus providing
the pre-clinical evidences for extremely attractive targets for novel therapeutic
interventions in WM. Of note, recent evidences have also approached and defined
the transcriptome profiling of WM cells, revealing a signature that mirrors the
somatic aberrations demonstrated within the tumor clone. A parallel research
field has also reported on microRNAs (miRNAs), highlighting the oncogenic role of
miRNA-155 in WM. In the present review, we focus on the latest reports on
genomics and miRNAs in WM, providing an overview of the clinical relevance of the
latest acquired knowledge about genomics and miRNA aberrations in WM.
PMID- 28423723
TI - Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects
the heart from doxorubicin-induced cardiomyopathy in mice.
AB - Doxorubicin is the chemotherapeutic drug of choice for a wide variety of cancers,
and cardiotoxicity is one of the major side effects of doxorubicin treatment. One
of the main cellular targets of doxorubicin in the heart is mitochondria.
Mitochondrial sirtuin, SIRT3 has been shown to protect against doxorubicin
induced cardiotoxicity. We have recently identified honokiol (HKL) as an
activator of SIRT3, which protects the heart from developing pressure overload
hypertrophy. Here, we show that HKL-mediated activation of SIRT3 also protects
the heart from doxorubicin-induced cardiac damage without compromising the tumor
killing potential of doxorubicin. Doxorubicin-induced cardiotoxicity is
associated with increased ROS production and consequent fragmentation of
mitochondria and cell death. HKL-mediated activation of SIRT3 prevented
Doxorubicin induced ROS production, mitochondrial damage and cell death in rat
neonatal cardiomyocytes. HKL also promoted mitochondrial fusion. We also show
that treatment with HKL blocked doxorubicin-induced cardiac toxicity in mice.
This was associated with reduced mitochondrial DNA damage and improved
mitochondrial function. Furthermore, treatments of mice, bearing prostrate tumor
xenografts, with HKL and doxorubicin showed inhibition of tumor growth with
significantly reduced cardiac toxicity. Our results suggest that HKL-mediated
activation of SIRT3 protects the heart from doxorubicin-induced cardiotoxicity
and represents a potentially novel adjunct for chemotherapy treatments.
PMID- 28423727
TI - Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins
against B-cell malignancies.
AB - CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or
acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL)
patients. The goal was to enhance rIT efficacy in vivo and to define a strong
combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined
with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or
continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or
paclitaxel alone was active, but all mice died from leukemia; when combined, 60%
of the mice achieved a sustained complete remission. Against MCL cells in vitro,
LR was more active than Moxe and the cells had to be exposed to rIT for more than
24 hours for them to die. To maintain high blood levels in vivo, LR was
administered continuously by 7-day pumps achieving a well-tolerated steady plasma
concentration of 45 ng/ml. In JeKo-1 xenografts, continuously administered LR was
14-fold more active than bolus doses and the combination with paclitaxel
additionally improved responses by 135-fold. Maintaining high rIT-plasma levels
greatly improves responses in the JeKo-1 model and paclitaxel substantially
enhances bolus and continuously infused rIT, supporting a clinical evaluation
against B-cell malignancies.
PMID- 28423728
TI - MiR-590-3p suppresses epithelial-mesenchymal transition in intrahepatic
cholangiocarcinoma by inhibiting SIP1 expression.
AB - The functional roles and clinical significances of miR-590-3p in ICC remain
unclear. In the current study, we investigated the expression of miR-590-3p in
tissues and sera of ICC by real-time quantitative polymerase chain reaction. We
found miR-590-3p was significantly down-regulated in the sera and tissues of ICC
patients, especially in those patients with lymph node metastasis or distant
metastasis. AUC curves and Cox proportional hazards mode revealed serum miR-590
3p could be novel diagnostic and prognostic biomarker for ICC patients. MiR-590
3p dramatically suppressed epithelial-mesenchymal transition, cell migration, and
invasion of ICC cells. SIP1 was identified as direct and functional target of miR
590-3p in ICC cells by luciferase assays. Finally, we found SIP1 expression was
inversely correlated with miR-590-3p and closely related to diminished survival
in ICC patients. These findings reveal functional and mechanistic roles of miR
590-3p and EMT activator SIP1 in the pathogenesis of ICC.
PMID- 28423729
TI - Digitalis use and risk of gastrointestinal cancers: A nationwide population-based
cohort study.
AB - BACKGROUND: Gastrointestinal cancers are characterized by a male predominance,
suggesting a role of sex hormones. We hypothesized that digitalis medication, due
to its estrogenic properties, decreases the risk of male-predominated
gastrointestinal cancers. RESULTS: Long -term digitalis use (>=2 years) was
followed by decreased risk for several gastrointestinal cancers, but associations
were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95%
confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with
an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01
3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer
(HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76),
but no such increase was found among long-term users. METHODS: We performed a
nationwide population-based cohort study in Sweden. Participants included 156,385
individuals using digitalis and a reference group of 551,933 users of organic
nitrates between 2005 and 2013, who were identified in the Swedish Prescribed
Drug Register. New diagnoses of gastrointestinal cancers were identified from the
Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis
users compared to users of organic nitrates were calculated from Cox proportional
hazards regression with adjustment for sex, age, municipality of residence and
comorbidity. CONCLUSIONS: This study suggests a decreased risk of male
predominated gastrointestinal cancers, particularly of liver cancer, in long-term
users of digitalis. Short-term use may be associated with an increased risk of
esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and
pancreatic cancer.The use of digitalis as preventive or therapeutic agents
remains to be fully evaluated.
PMID- 28423730
TI - The SCLtTAxBCR-ABL transgenic mouse model closely reflects the differential
effects of dasatinib on normal and malignant hematopoiesis in chronic phase-CML
patients.
AB - The second generation tyrosine kinase inhibitor (TKI) dasatinib is a clinically
approved drug for chronic myeloid leukemia (CML) as well as Ph+ acute
lymphoblastic leukemia. In addition to its antileukemic effects, dasatinib was
shown to impact on normal hematopoiesis and cells of the immune system.Due to the
fact that the murine in vivo studies so far have not been performed in a chronic
phase CML model under steady-state conditions, our aim was to study the
hematopoietic effects of dasatinib (20 mg/kg p.o.) in BCR-ABL expressing
SCLtTAxBCR-ABL double transgenic (dtg) mice. Dasatinib robustly antagonized the
CML phenotype in vivo in our transgenic mouse model, and this effect included
both mature and immature cell populations. However, similar to patients with CML,
the fraction of LinnegSca-1+KIT+CD48negCD150+ hematopoietic stem cells was not
reduced by dasatinib treatment, suggesting that these cells are not oncogene
addicted. Moreover, we observed differential effects of dasatinib in these
animals as compared to wild-type (wt) animals: while granulocytes were
significantly reduced in dtg animals, they were increased in wt mice. And Ter119+
erythrocytic and B220+ B cells were increased in dtg mice but decreased in wt
mice. Finally, while dasatinib induced a shift from CD49b/NK1.1 positive NK cells
from the bone marrow to the spleen in wt animals, there was no change in dtg
mice. In conclusion, the present mouse model provides a useful tool to study
mechanisms of TKI resistance and dasatinib-associated beneficial effects and
adverse events.
PMID- 28423731
TI - A multifunctional lipid nanoparticle for co-delivery of paclitaxel and curcumin
for targeted delivery and enhanced cytotoxicity in multidrug resistant breast
cancer cells.
AB - The objective of the work was to develop a multifunctional nanomedicine based on
a folate-conjugated lipid nanoparticles loaded with paclitaxel and curcumin. The
novel system combines therapeutic advantageous of efficient targeted delivery via
folate and timed-release of curcumin and paclitaxel via 2-hydroxypropyl-beta
cyclodextrin, thereby overcoming multidrug resistance in breast cancer cells (MCF
7/ADR). The faster release of curcumin from the folate-conjugated curcumin and
paclitaxel-loaded lipid nanoparticles enables sufficient p-glycoprotein
inhibition, which allows increased cellular uptake and cytotoxicity of
paclitaxel. In western blot assay, curcumin can efficiently inhibit the
expression of p-glycoprotein, conformed the enhancement of cytotoxicity by
paclitaxel. Furthermore, folate-conjugated curcumin and paclitaxel-loaded lipid
nanoparticles exhibited increased uptake of paclitaxel and curcumin into MCF
7/ADR cells through the folate receptor-mediated internalization. Taken together,
these results indicate that folate-conjugated curcumin and paclitaxel-loaded
lipid nanoparticles enables the enhanced, folate-targeted delivery of multiple
anticancer drugs by inhibiting the multi-drug resistance efficiently, which may
also serve as a useful nano-system for co-delivery of other anticancer drugs.
PMID- 28423733
TI - Nanocrystals of a new camptothecin derivative WCN-21 enhance its solubility and
efficacy.
AB - WCN-21 is a new camptothecin derivative we synthesized and has desirable anti
tumor efficacy, but its aqueous solubility is very low and hurdles the further
evaluation and development. In this study, we prepared nanocrystals of WCN-21
through a bottom-up approach to enhance its solubility and obtained WCN-21
nanorods (WND) and nanospheres (WNP). We investigated the crystallization of WND
and WNP in different temperature and solvents and found that both temperature and
solvents affect the crystal shapes and sizes. We prepared WND at 50 degrees C and
DMSO : H2O 1: 50 and WNP at 25 degrees C and DMSO : H2O 1: 100 and found they
were dispersed evenly in water with average hydrodynamic diameters 337 and 231
nm, respectively. WND and WNP increased the solubility of WCN-21 from extreme
insolubility to more than 9 and 11 mM in H2O or PBS, respectively. In vitro
studies showed that WND and WNP enhanced the uptake of WCN-21 in tumor cells by 3
and 9 folds, and increased cytotoxicity of WCN-21 in comparison with free WCN-21
by 5 and 6 folds, respectively. In xenograft tumor mice, intravenous injection of
WND and WNP enhanced the accumulation of WCN-21 in tumor tissues and improved the
anti-tumor efficacy. In addition, WND and WNP did not increase the toxicity of
WCN-21 in mice. Therefore, nanocrystal is a robust tool to improve the solubility
of insoluble drugs and holds a great potential in the application of drug
development.
PMID- 28423732
TI - Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer
metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.
AB - Metastasis of cancer cells is a key impediment to favorable outcomes of cancer
treatment. Functional roles of long noncoding RNAs in several biological
processes, including metastasis, have recently been discovered. In our previous
work, we reported a positive correlation of increased expression of linc00673 in
NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased
proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we
demonstrate that ectopic expression of linc00673 promotes migration and invasion
of NSCLC cells. Furthermore, our results indicate that linc00673 could silence
HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter
regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC
cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the
first time identified the role of lin00673 in promoting invasion and migration of
NSCLC cells. Insights from this study may help to identify novel therapeutic
targets for NSCLC.
PMID- 28423734
TI - GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer:
database mining for GATA family members in malignancies.
AB - GATA transcription factors are zinc finger DNA binding proteins that activate
transcription during development and cell differentiation. To date, 7 members of
GATA family have been reported. However, the expression patterns and the exact
roles of distinct GATA family members contributing to tumorigenesis and
progression of breast cancer (BC) remain to be elucidated. Here, we studied the
expression of GATA transcripts in a variety of tumor types compared with the
normal controls using the ONCOMINE and GOBO databases, along with their
corresponding expression profiles in an array of cancer cell lines through CCLE
analysis. Based on Kaplan-Meier plotter, we further investigated the prognostic
values of GATA members specifically high expressed in BC patients. It was found
that, when compared with normal tissues, GATA3 and TRPS1 were distinctly high
expressed in BC patients among all GATA members. GATA3 expression was
significantly associated with ESR1, while TRPS1 was correlated with ERBB2. In
survival analysis, GATA3 and TRPS1 mRNA high expressions were correlated to
better survival in BC patients, and TRPS1 high expression was significantly
associated with longer RFS in patients who have received chemotherapy. These
results suggest that GATA3 and TRPS1 are distinct biomarkers and essential
prognostic factors for breast cancer.
PMID- 28423736
TI - Laminarin promotes anti-cancer immunity by the maturation of dendritic cells.
AB - This research evaluates the effects of laminarin on the maturation of dendritic
cells and on the in vivo activation of anti-cancer immunity. In vivo treatment of
C56BL/6 mice with laminarin increased the expression levels of co-stimulatory
molecules and the production of pro-inflammatory cytokines in spleen dendritic
cells. Laminarin enhanced ovalbumin antigen presentation in spleen dendritic
cells and promoted the proliferation of OT-I and OT-II T cells. Laminarin also
induced the maturation of dendritic cells in tumor-draining lymph nodes and
protected interferon-gamma and tumor necrosis factor-alpha and proliferation of
OT-I and OT-II T cells in tumors. The combination treatment of laminarin and
ovalbumin inhibited B16-ovallbumin melanoma tumor growth and its liver metastasis
by antigen-specific immune activation, including cytotoxic T lymphocyte
activation and interferon-gamma production. Thus, these data demonstrated the
potential of laminarin as a new and useful immune stimulatory molecule for use in
cancer immunotherapy.
PMID- 28423735
TI - The long non-coding RNA NONHSAG026900 predicts prognosis as a favorable biomarker
in patients with diffuse large B-cell lymphoma.
AB - Long non-coding RNAs are known to be involved in cancer progression, but their
biological functions and prognostic values are still largely unexplored in
diffuse large B-cell lymphoma. In this study, long non-coding RNAs expression was
characterized in 1,403 samples including normal and diffuse large B-cell lymphoma
by repurposing 7 microarray datasets. Compared with any stage of normal B cells,
NONHSAG026900 expression was significantly decreased in tumor samples. And in
germinal center B-cell subtype, the significantly higher expression of
NONHSAG026900 indicated it was a favorable prognosis biomarker. Then the
prognostic power of NONHSAG026900 was validated with another independent dataset
and NONHSAG026900 improved the predictive power of International Prognostic Index
as an independent factor. Moreover, functional prediction and validation
demonstrated that NONHSAG026900 could inhibit cell cycle activity to restrain
tumor proliferation. These findings identified NONHSAG026900 as a novel
prognostic biomarker and offered a new therapeutic target for diffuse large B
cell lymphoma patients.
PMID- 28423737
TI - RMP promotes epithelial-mesenchymal transition through NF-kappaB/CSN2/Snail
pathway in hepatocellular carcinoma.
AB - Epithelial-mesenchymal transition (EMT) is a significant risk factor for
metastasis in hepatocellular carcinoma (HCC) patients and with poor prognosis. In
this study, we demonstrate the key role of RPB5-mediating protein (RMP) in EMT of
HCC cells and the mechanism by which RMP promote EMT. RMP increases migration,
invasion, and the progress of EMT of HCC cells, which facilitates the
accumulation of Snail, a transcriptional repressor involved in EMT initiation. NF
kappaB is activated by RMP, which directly promotes the expression of COP9
signalosome 2 (CSN2) to repress the degradation of Snail. Pulmonary metastases
mouse model demonstrates that RMP induces metastasis in vivo. Immunohistochemical
analysis of human HCC tissues confirms the correlation of RMP with the expression
of E-cadherin, p65, CSN2 and Snail in vivo. Collectively, these findings indicate
that RMP promotes EMT and HCC metastasis through NF-kappaB/CSN2/Snail pathway.
These results suggest that RMP and p65 may serve as potential candidates of the
targets in the treatment of metastatic HCC.
PMID- 28423738
TI - LncRNA Snhg1, a non-degradable sponge for miR-338, promotes expression of proto
oncogene CST3 in primary esophageal cancer cells.
AB - Competing endogenous RNA (ceRNA) is a newly proposed mechanism that describes a
crosstalk among lncRNAs, mRNAs and their shared miRNAs. In this study, the role
of miR-338-3p (miR-338) in the progression of esophageal cancer and its involve
in the ceRNA regulatory circuit lncRNA-Snhg1/CST3 were explored. MiR-338
displayed a 30% decreased expression in esophageal squamous cell carcinoma
tissues compared with the adjacent. Then, proto-oncogene CST3 was predicted and
validated as a target gene of miR-338. Gain-and-loss-function experiments
indicated that miR-338 suppressed expression of CST3 protein (also Cystatin C,
CysC), promoted expression of apoptotic proteins caspase-8/3, attenuated
esophageal carcinoma cell growth and induced its apoptosis. In addition, lncRNA
Snhg1 was significantly upregulated in esophageal carcinoma tissues and promoted
esophageal carcinoma cell growth. Furthermore, our results from bioinformatics,
luciferase reporter gene and RNA pull-down assays indicated that Snhg1 could be
directly bound by miR-338. Snhg1 acted as a non-degradable sponge to relieve the
suppression on CST3 caused by miR-338. In conclusion, lncRNA-Snhg1 promoted cell
proliferation by acting as a non-degradable sponge for the tumor suppressor miR
338 in esophageal cancer cells.
PMID- 28423740
TI - Prognosis of surgery combined with different adjuvant therapies in esophageal
cancer treatment: a network meta-analysis.
AB - : This network meta-analysis was conducted to assess whether the efficacy of
surgery with adjuvant therapies, including radiotherapy (RT+S), chemotherapy
(CT+S), and chemoradiotherapy (CRT+S) have better performance in esophageal
cancer treatment and management. PubMed and EMBASE were used to search for
relevant trials. Both conventional pair-wise and network meta-analyses were
carried out. The surface under the cumulative ranking curve (SUCRA) was used to
rank interventions based on the efficacy of the treatment method. As for 3-year
overall survival (OS), CRT+S showed the highest efficacy (CRT+S vs. SURGERY:
HR=0.81, 95% CrI =0.73-0.90; CRT+S vs. CT+S: HR=0.82, 95% CrI =0.70-0.95; CRT+S
vs. RT+S: HR=0.77, 95% CrI =0.62-0.95). For disease-free survival, CRT+S showed
efficacy over CT+S ((HR =0.70, 95% CrI =0. 59-0.83). In conclusion, CRT+S showed
a better performance for survival outcomes and ranks best among all therapies.
The results of our study can provide guidance for medical decisions and treatment
options that may help clinical practitioners improve the efficacy of EC
treatment.
PMID- 28423741
TI - Lenalidomide and the risk of serious infection in patients with multiple myeloma:
a systematic review and meta-analysis.
AB - The immunomodulatory drug lenalidomide is highly effective against newly
diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even
fatal infections have been associated with its use. In this meta-analysis, we
assessed the overall risk of infection to MM patients treated with lenalidomide.
Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected
from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial
Registration website, and from meeting abstracts and virtual presentations at the
American Society of Clinical Oncology. Main outcome measures were overall
incidence, relative risk (RR), and 95% confidence intervals (CIs) of reported
infection events. Fixed-effect or random-effect models were used in the
statistical analyses, depending on the between-study heterogeneity. The overall
incidence of high-grade infection was 14.32% (95% CI: 12.08%-16.90%) and high
grade infection's pooled RR was 2.23 (95% CI: 1.71-2.91, P < 0.0001) for all 11
studies evaluated. No evidence of publication bias for the incidence of high
grade infection was detected using Begg's funnel plot and Egger's test (P = 0.2;
95% CI: -1.70, 1.23). From this meta-analysis, it appears lenalidomide use is
associated with an increased risk of high-grade infection. Moreover, fatal
infection events occurred only in patients treated with lenalidomide; no
infection-related deaths were observed among controls. These data indicate that
accurate diagnosis and optimal management of infection in MM patients treated
with lenalidomide could be critical for treatment efficacy.
PMID- 28423743
TI - 1. Connected and Digital Health.
PMID- 28423744
TI - Design and Validation of a Platform to Evaluate mHealth Apps.
AB - Emerging technologies show great potential in the field of patient care. One such
technology is mobile heath applications (mhealth apps), which have exploded in
number and variety in recent years, and offer great promise in the ability to
collect and monitor patient health data. Despite their apparent success in
proliferation and user adoption, these applications struggle to integrate into
the primary care system and there is scant information regarding their efficacy
to effect patient behavior and consequently health outcomes. In this paper we
investigate the potential of a promising clinical evaluation methodology,
response adaptive randomized clinical trials, to rapidly and effectively evaluate
the efficacy and effectiveness of mhealth apps and to personalize mhealth app
selection to individualize patient benefit. Diabetes prevention provides the use
case for evaluating the case for and against response-adaptive randomized trials.
PMID- 28423745
TI - Reasoning and Data Representation in a Health and Lifestyle Support System.
AB - Case-based reasoning and data interpretation is an artificial intelligence
approach that capitalizes on past experience to solve current problems and this
can be used as a method for practical intelligent systems. Case-based data
reasoning is able to provide decision support for experts and clinicians in
health systems as well as lifestyle systems. In this project we were focusing on
developing a solution for healthy ageing considering daily activities, nutrition
as well as cognitive activities. The data analysis of the reasoner followed state
of the art guidelines from clinical practice. Guidelines provide a general
framework to guide clinicians, and require consequent background knowledge to
become operational, which is precisely the kind of information recorded in
practice cases; cases complement guidelines very well and helps to interpret
them. It is expected that the interest in case-based reasoning systems in the
health.
PMID- 28423742
TI - Novel potential predictive markers of sunitinib outcomes in long-term responders
versus primary refractory patients with metastatic clear-cell renal cell
carcinoma.
AB - BACKGROUND: Several potential predictive markers of efficacy of targeted agents
in patients with metastatic renal cell carcinoma (mRCC) have been identified.
Interindividual heterogeneity warrants further investigation. PATIENTS AND
METHODS: Multicenter, observational, retrospective study in patients with clear
cell mRCC treated with sunitinib. Patients were classified in two groups: long
term responders (LR) (progression-free survival (PFS)>=22 months and at least
stable disease), and primary refractory (PR) (progressive disease within 3-months
of sunitinib onset). Objectives were to compare baseline clinical factors in both
populations and to correlate tumor expression of selected signaling pathways
components with sunitinib PFS. RESULTS: 123 patients were analyzed (97 LR, 26
PR). In the LR cohort, overall response rate was 79% and median duration of best
response was 30 months. Median PFS and overall survival were 43.2 (95% confidence
intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At
baseline PR patients had a significantly lower proportion of nephrectomies,
higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time
to and higher presence of metastases, and increased Fuhrman grade. Higher levels
of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated
populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of
hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged
survival. No statistical significant associations between hsa-miR-23b or hsa-miR
27b and the expression of c-Met were found. CONCLUSIONS: Certain mRCC patients
treated with sunitinib achieve extremely long-term responses. Favorable baseline
hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa
miR-27b, hsa-miR-23b and hsa-miR-628-5p could be potentially used as biomarkers
of sunitinib response.
PMID- 28423746
TI - Feasibility of Representing a Danish Microbiology Model Using FHIR.
AB - Achieving interoperability in health is a challenge and requires standardization.
The newly developed HL7 standard: Fast Healthcare Interoperability Resources
(FHIR) promises both flexibility and interoperability. This study investigates
the feasibility of expressing a Danish microbiology message model content in FHIR
to explore whether complex in-use legacy models can be migrated and what
challenges this may pose. The Danish microbiology message model (the DMM) is used
as a case to illustrate challenges and opportunities accosted with applying the
FHIR standard. Mapping of content from DMM to FHIR was done as close as possible
to the DMM to minimize migration costs except when the structure of the content
did not fit into FHIR. From the DMM a total of 183 elements were mapped to FHIR.
75 (40.9%) elements were modeled as existing FHIR elements and 96 (52.5%)
elements were modeled as extensions and 12 (6.6%) elements were deemed
unnecessary because of build-in FHIR characteristics. In this study, it was
possible to represent the content of a Danish message model using HL7 FHIR.
PMID- 28423747
TI - Establishment of Requirements and Methodology for the Development and
Implementation of GreyMatters, a Memory Clinic Information System.
AB - INTRODUCTION: The aim of the paper is to establish the requirements and
methodology for the development process of GreyMatters, a memory clinic system,
outlining the conceptual, practical, technical and ethical challenges, and the
experiences of capturing clinical and research oriented data along with the
implementation of the system. METHODS: The methodology for development of the
information system involved phases of requirements gathering, modeling and
prototype creation, and 'bench testing' the prototype with experts. The standard
Institute of Electrical and Electronics Engineers (IEEE) recommended approach for
the specifications of software requirements was adopted. An electronic health
record (EHR) standard, EN13606 was used, and clinical modelling was done through
archetypes and the project complied with data protection and privacy legislation.
RESULTS: The requirements for GreyMatters were established. Though the initial
development was complex, the requirements, methodology and standards adopted made
the construction, deployment, adoption and population of a memory clinic and
research database feasible. The electronic patient data including the assessment
scales provides a rich source of objective data for audits and research and to
establish study feasibility and identify potential participants for the clinical
trials. CONCLUSION: The establishment of requirements and methodology, addressing
issues of data security and confidentiality, future data compatibility and
interoperability and medico-legal aspects such as access controls and audit
trails, led to a robust and useful system. The evaluation supports that the
system is an acceptable tool for clinical, administrative, and research use and
forms a useful part of the wider information architecture.
PMID- 28423748
TI - Nurses' Perspectives on In-Home Monitoring of Elderlies's Motion Pattern.
AB - In-home monitoring systems have been proposed to support aging in place and
facilitate home care service. Through a qualitative approach the study explores
nurses' existing challenges and perspectives of an in-home monitoring system.
Results indicate that nurses base care decisions on multiple, and sometimes,
unreliable information sources. However, access to information about elderlies'
physical motion could support the care planning process by reducing ambiguity and
raising attention. Hence, a simple and affordable system that largely relies on
nurses to interpret the sensed data could bring additional value.
PMID- 28423749
TI - Monitoring Activities Related to Medication Adherence in Ambient Assisted Living
Environments.
AB - A recent trend in healthcare is to motivate patients to self-manage their health
conditions in home-based settings. Medication adherence is an important aspect in
disease self-management since sub-optimal medication adherence by the patient can
lead to serious healthcare costs and discomfort for the patient. In order to
alleviate the limitations of self-reported medication adherence, we can use
ambient assistive living (AAL) technologies in smart environments. Activity
recognition services allow to retrieve self-management information related to
medication adherence in a less intrusive way. By remotely monitor compliance with
medication adherence, self-management program's interventions can be tailored and
adapted based on the observed patient's behaviour. To address this challenge, we
present an AAL framework that monitor activities related to medication adherence.
PMID- 28423750
TI - Design, Implementation and Operation of a Reading Center Platform for Clinical
Studies.
AB - Clinical reading centers provide expertise for consistent, centralized analysis
of medical data gathered in a distributed context. Accordingly, appropriate
software solutions are required for the involved communication and data
management processes. In this work, an analysis of general requirements and
essential architectural and software design considerations for reading center
information systems is provided. The identified patterns have been applied to the
implementation of the reading center platform which is currently operated at the
Center of Ophthalmology of the University Hospital of Tubingen.
PMID- 28423751
TI - Web Validation Service for Ensuring Adherence to the DICOM Standard.
AB - The DICOM Standard has been fundamental for ensuring the interoperability of
Picture Archive and Communications Systems (PACS). By compiling rigorously to the
standard, medical imaging equipment and applications from different vendors can
share their data, and create integrated workflows which contributes to better
quality healthcare services. However, DICOM is a complex, flexible and very
extensive standard. Thus, it is difficult to attest the conformity of data
structures produced by DICOM applications resulting in unexpected behaviors,
errors and malfunctions. Those situations may be critical for regular PACS
operation, resulting in serious losses to the healthcare enterprise. Therefore,
it is of paramount importance that application vendors and PACS administrators
are confident that their applications follow the standard correctly. In this
regard, we propose a method for validating the compliance of PACS application
with the DICOM Standard. It can capture the intricate dependency structure of
DICOM modules and data elements using a relatively simple description language.
The modular nature of our method allows describing each DICOM module, their
attributes, and dependencies on a re-usable basis. As a result, our validator is
able to encompass the numerous modules present in DICOM, as well as keep up with
the emergence of new ones.
PMID- 28423752
TI - A Decision Support System for Cardiac Disease Diagnosis Based on Machine Learning
Methods.
AB - This paper proposes a decision support system for screening pediatric cardiac
disease in primary healthcare centres relying on the heart sound time series
analysis. The proposed system employs our processing method which is based on the
hidden Markov model for extracting appropriate information from the time series.
The binary output resulting from the method is discriminative for the two classes
of time series existing in our databank, corresponding to the children with heart
disease and the healthy ones. A total 90 children referrals to a university
hospital, constituting of 55 healthy and 35 children with congenital heart
disease, were enrolled into the study after obtaining the informed consent.
Accuracy and sensitivity of the method was estimated to be 86.4% and 85.6%,
respectively, showing a superior performance than what a paediatric cardiologist
could achieve performing auscultation. The method can be easily implemented using
mobile and web technology to develop an easy-to-use tool for paediatric cardiac
disease diagnosis.
PMID- 28423753
TI - Severity Summarization and Just in Time Alert Computation in mHealth Monitoring.
AB - Mobile health is fast evolving into a practical solution to remotely monitor high
risk patients and deliver timely intervention in case of emergencies. Building
upon our previous work on a fast and power efficient summarization framework for
remote health monitoring applications, called RASPRO (Rapid Alerts Summarization
for Effective Prognosis), we have developed a real-time criticality detection
technique, which ensures meeting physician defined interventional time. We also
present the results from initial testing of this technique.
PMID- 28423754
TI - Towards Safe and Efficient Child Primary Care - Gaps in the Use of Unique
Identifiers in Europe.
AB - In order to provide for best possible child health care, timely access to all
relevant medical data is of vital importance. The aim of this study is to
investigate the use of unique identifiers, a key instrument in this regard, in
the countries of Europe. A survey was carried out in all 28 European Member
States plus 2 European Economic Area countries in 2015, and refreshed in 2016. In
23 countries unique identifiers are used to link children's health records. Five
countries indicated they currently do not link child health records, and two have
no such plans. There is variety as regards the type of number and the issuing
process.
PMID- 28423755
TI - Why Are Children's Interests Invisible in European National E-Health Strategies?
AB - Harnessing the power of IT solutions in child primary care requires strategic
thought at national level, and good health care delivery needs this support. The
aim of this study was to investigate whether children's needs are considered in
national e-health strategies in Europe. In 2016, a survey was carried out in all
28 European Member States plus 2 European Economic Area countries. Sixteen
countries fail to mention children's needs at all. Only eleven of 27 countries
mention children and adolescents in their national e-health strategy documents
ranging from mere data protection concerns to comprehensive IT approaches for the
improvement of child primary care.
PMID- 28423756
TI - Shared Decision Making via Personal Health Record Technology for Routine Use of
Diabetic Youth: A Study Protocol.
AB - Engaging patients in the self-management decision-making provides opportunities
for positive health outcomes. The process of shared decision making (SDM) is
touted as the pinnacle of patient-centred care, yet it has been difficult to
implement in practice. Access to tools resulting from the integration of all
health data and clinical evidence, and an ease of communications with care
providers are needed to engage patients in decision making. Personal health
record (PHR) technology is a promising approach for overcoming such barriers. Yet
there is a scarcity of studies on system design for SDM via PHR. This paper
describes a study protocol to identify functional requirements of PHR for
facilitating SDM and factors that would influence the embedding of the proposed
system in clinical practice.
PMID- 28423757
TI - A Medication Reminder Mobile App: Does It Work for Different Age Ranges.
AB - Successful medication adherence particularly in elderly with chronic diseases
will improve their self-management. Medication reminder systems could be useful
to improve this adherence. This study consists of two phases, designing a mobile
medical app based on Android platform and then its evaluation. To develop this
application, first, the use case scenarios have been hypothesized in partnership
with health professionals and patients used to take medications daily. Unified
Modeling Language was used to model the use cases. The evaluation was performed
with usability testing and efficacy testing. The results show that the app was
well accepted both in young people and older adults. Engaging target users and
health professionals in the conception and development of a health-related app
could have better results in the usability and the efficacy of the app.
PMID- 28423758
TI - Internet of Things in Health Trends Through Bibliometrics and Text Mining.
AB - Recently a new buzzword has slowly but surely emerged, namely the Internet of
Things (IoT). The importance of IoT is identified worldwide both by organisations
and governments and the scientific community with an incremental number of
publications during the last few years. IoT in Health is one of the main pillars
of this evolution, but limited research has been performed on future visions and
trends. Thus, in this study we investigate the longitudinal trends of Internet of
Things in Health through bibliometrics and use of text mining. Seven hundred
seventy eight (778) articles were retrieved form The Web of Science database from
1998 to 2016. The publications are grouped into thirty (30) clusters based on
abstract text analysis resulting into some eight (8) trends of IoT in Health.
Research in this field is obviously obtaining a worldwide character with specific
trends, which are worth delineating to be in favour of some areas.
PMID- 28423759
TI - Developing the Safety Case for MediPi: An Open-Source Platform for Self
Management.
AB - mHealth and Telehealth technologies are increasingly used to provide
personalised, interactive and timely access to health data, thereby helping
patients take a more active role in their care process. However, similar to any
intervention, the use of these technologies has to be assured to justify that
they do not compromise patient safety. In this paper, we discuss the development
of a safety case for MediPi; a research prototype for a low-cost open-source
digital platform that collects physiological data from patients, at home, and
makes it available to decision-support systems used by clinicians. We identify
potential hazardous failures associated with the use of MediPi and examine
current risk controls. We also explore the modular structure of the overall
safety case of the platform. We conclude with a discussion of patient safety
challenges related to the unsupervised nature of the care setting and the use of
commercial off-the-shelf personal devices.
PMID- 28423760
TI - UK Health and Social Care Case Studies: Iterative Technology Development.
AB - As a result of increasing demand in the face of reducing resources, technology
has been implemented in many social and health care services to improve service
efficiency. This paper outlines the experiences of deploying a 'Software as a
Service' application in the UK social and health care sectors. The case studies
demonstrate that every implementation is different, and unique to each
organisation. Technology design and integration can be facilitated by ongoing
engagement and collaboration with all stakeholders, flexible design, and
attention to interoperability to suit services and their workflows.
PMID- 28423762
TI - Predicting the Pathogenic Impact of Sequence Variation in the Human Genome.
AB - Sequencing data will become widely available in clinical practice within the near
future. Uptake of sequence data is currently being stimulated within the UK
through the government-funded 100,000 genomes project (Genomics England), with
many similar initiatives being planned and supported internationally. The
analysis of the large volumes of data derived from sequencing programmes poses a
major challenge for data analysis. In this paper we outline progress we have made
in the development of predictors for estimating the pathogenic impact of single
nucleotide variants, indels and haploinsufficiency in the human genome. The
accuracy of these methods is enhanced through the development of disease-specific
predictors, trained on appropriate data, and used within a specific disease
context. We outline current research on the development of disease-specific
predictors, specifically in the context of cancer research.
PMID- 28423763
TI - Learning Healthcare System for the Prescription of Genetic Testing in the
Gynecological Cancer Risk.
AB - Clinical evidence demonstrates that BRCA 1 and BRCA2 mutations can develop a
gynecological cancer but genetic testing has a high cost to the healthcare
system. Besides, several studies in the literature indicate that performing these
genetic tests to the population is not cost-efficient. Currently, our physicians
do not have a system to provide them the support for prescribing genetic tests. A
Decision Support System for prescribing these genetic tests in BRCA1 and BRCA2
and preventing gynecological cancer risks has been designed, developed and
deployed in the Virgen del Rocio University Hospital (VRUH). The technological
architecture integrates a set of open source tools like Mirth Connect,
OpenClinica, OpenCDS, and tranSMART in addition to several interoperability
standards. The system allows general practitioners and gynecologists to classify
patients as low risk (they do not require a specific treatment) or high risk
(they should be attended by the Genetic Council). On the other hand, by means of
this system we are also able to standardize criteria among professionals to
prescribe these genetic tests. Finally, this system will also contribute to
improve the assistance for this kind of patients.
PMID- 28423764
TI - An Automatic Approach for Analyzing Treatment Effectiveness Based on Medication
Hierarchy - The Myocardial Infarction Case Study.
AB - Treatment effectiveness plays a fundamental role in patient therapies. In most
observational studies, researchers often design an analysis pipeline for a
specific treatment based on the study cohort. To evaluate other treatments in the
data set, much repeated and multifarious work including cohort construction,
statistical analysis need to be done. In addition, as treatments are often with
an intrinsic hierarchical relationship, many rational comparable treatment pairs
can be derived as new treatment variables besides the original single treatment
one from the original cohort data set. In this paper, we propose an automatic
treatment effectiveness analysis approach to solve this problem. With our
approach, clinicians can assess the effect of treatments not only more
conveniently but also more thoroughly and comprehensively. We applied this method
to a real world case of estimating the drug effectiveness on Chinese Acute
Myocardial Infarction (CAMI) data set and some meaningful results are obtained
for potential improvement of patient treatments.
PMID- 28423765
TI - Evaluation of Machine Learning Methods to Predict Coronary Artery Disease Using
Metabolomic Data.
AB - Metabolomic data can potentially enable accurate, non-invasive and low-cost
prediction of coronary artery disease. Regression-based analytical approaches
however might fail to fully account for interactions between metabolites, rely on
a priori selected input features and thus might suffer from poorer accuracy.
Supervised machine learning methods can potentially be used in order to fully
exploit the dimensionality and richness of the data. In this paper, we
systematically implement and evaluate a set of supervised learning methods (L1
regression, random forest classifier) and compare them to traditional regression
based approaches for disease prediction using metabolomic data.
PMID- 28423766
TI - Dermatology Disease Prediction Based on Two Step Cascade Genetic Algorithm
Optimization of ANFIS Parameters.
AB - The aim of this study is to present novel algorithms for prediction of
dermatological disease using only dermatological clinical features and diagnoses
collected in real conditions. A combination of the Adaptive Neuro-Fuzzy Inference
Systems (ANFIS) and Genetic algorithm (GA) for ANFIS subtractive clustering
parameter optimization has been suggested for the first level of fuzzy model
optimization. After that, a genetic optimized ANFIS fuzzy structure is used as
input in GA for the second level of fuzzy model optimization. We used double 2
fold Cross validation for generating different validation sets for model
improvements. Our approach is performed in the MATLAB environment. We compared
results with the other studies. The results confirm that the proposed model
achieves accuracy rates which are higher than the one with the previous model.
PMID- 28423767
TI - Querying EHRs with a Semantic and Entity-Oriented Query Language.
AB - While the digitization of medical documents has greatly expanded during the past
decade, health information retrieval has become a great challenge to address many
issues in medical research. Information retrieval in electronic health records
(EHR) should also reduce the difficult tasks of manual information retrieval from
records in paper format or computer. The aim of this article was to present the
features of a semantic search engine implemented in EHRs. A flexible, scalable
and entity-oriented query language tool is proposed. The program is designed to
retrieve and visualize data which can support any Conceptual Data Model. The
search engine deals with structured and unstructured data, for a sole patient
from a caregiver perspective, and for a number of patients (e.g. epidemiology).
Several types of queries on a test database containing 2,000 anonymized patients
EHRs (i.e. approximately 200,000 records) were tested. These queries were able to
accurately treat symbolic, textual, numerical and chronological data.
PMID- 28423768
TI - Evaluation of the Terminology Coverage in the French Corpus LiSSa.
AB - Extracting concepts from medical texts is a key to support many advanced
applications in medical information retrieval. Entity recognition in French texts
is moreover challenged by the availability of many resources originally developed
for English texts. This paper proposes an evaluation of the terminology coverage
in a corpus of 50,000 French articles extracted from the bibliographic database
LiSSa. This corpus was automatically indexed with 32 health terminologies,
published in French or translated. Then, the terminologies providing the best
coverage of these documents were determined. The results show that major
resources such as the NCI and SNOMED CT thesauri achieve the largest annotation
of the corpus while specific French resources prove to be valuable assets.
PMID- 28423769
TI - Linked Data Applications Through Ontology Based Data Access in Clinical Research.
AB - Clinical care and research data are widely dispersed in isolated systems based on
heterogeneous data models. Biomedicine predominantly makes use of connected
datasets based on the Semantic Web paradigm. Initiatives like Bio2RDF created
Resource Description Framework (RDF) versions of Omics resources, enabling
sophisticated Linked Data applications. In contrast, electronic healthcare
records (EHR) data are generated and processed in diverse clinical subsystems
within hospital information systems (HIS). Usually, each of them utilizes a
relational database system with a different proprietary schema. Semantic
integration and access to the data is hardly possible. This paper describes ways
of using Ontology Based Data Access (OBDA) for bridging the semantic gap between
existing raw data and user-oriented views supported by ontology-based queries.
Based on mappings between entities of data schemas and ontologies data can be
made available as materialized or virtualized RDF triples ready for querying and
processing. Our experiments based on CentraXX for biobank and study management
demonstrate the advantages of abstracting away from low level details and
semantic mediation. Furthermore, it becomes clear that using a professional
platform for Linked Data applications is recommended due to the inherent
complexity, the inconvenience to confront end users with SPARQL, and scalability
and performance issues.
PMID- 28423770
TI - Epidemiological Models Lacking Process Noise Can Be Overconfident.
AB - Mathematic models of epidemics are the key tool for predicting future course of
disease in a population and analyzing the effects of possible intervention
policies. Typically, models that produce deterministic are applied for making
predictions and reaching decisions. Stochastic modeling methods present an
alternative. Here, we demonstrate by example why it is important that stochastic
modeling be used in population health decision support systems.
PMID- 28423771
TI - Disentangling Prognostic and Predictive Biomarkers Through Mutual Information.
AB - We study information theoretic methods for ranking biomarkers. In clinical
trials, there are two, closely related, types of biomarkers: predictive and
prognostic, and disentangling them is a key challenge. Our first step is to
phrase biomarker ranking in terms of optimizing an information theoretic
quantity. This formalization of the problem will enable us to derive rankings of
predictive/prognostic biomarkers, by estimating different, high dimensional,
conditional mutual information terms. To estimate these terms, we suggest
efficient low dimensional approximations. Finally, we introduce a new
visualisation tool that captures the prognostic and the predictive strength of a
set of biomarkers. We believe this representation will prove to be a powerful
tool in biomarker discovery.
PMID- 28423772
TI - IntegrIT - Towards Utilizing the Swedish National Health Information Exchange
Platform for Clinical Research.
AB - This paper describes how the Swedish national Health Information Exchange
platform can be used to facilitate clinical research in the future. Different e
services for different user groups are being developed using a user-centered
design approach. The main user groups are study participants, clinical
researchers and healthcare professionals. The different e-services are based on
an in-depth analysis of the clinical research process, and the main identified
needs relate to recruitment of study participants, access to clinical data from
different sources as well as improved tools for patients' self-reporting. The
national Swedish HIE platform has the potential to enable a seamless connection
between patients/citizens as study participants, health care professionals and
everyday clinical work and clinical researchers in both academia and industry.
PMID- 28423773
TI - Introducing a Method for Transformation of Paper-Based Research Data into Concept
Based Representation with openEHR.
AB - Combining research data and clinical routine data is a chance for medical
research. We present our method for the transformation of paper-based research
data into a concept-based representation. With this representation the study data
from research projects can be combined with data from clinical tools with less
integration effort. We applied and verified our method using data from a current
research study. In this paper we also show our main challenges and lessons
learned. Clinical assessment data and study diaries from a long term study (n=24,
3 months observation time each, 17 different clinical assessments) stored on
paper were used as the data set. An openEHR-based electronical health record
platform was adapted for acquisition and representation of the research data. To
avoid transcription errors, the data was entered twice by different student
assistants. A third compared and corrected both data sets. Content models (17
archetypes and five templates from openEHR concept) based on clinical assessments
were created manually. Web forms for data entry were created automatically on the
basis of this concept-based content models. Additionally, form functionalities to
support data entry and comparison were implemented. In total, 829 compositions
were entered by the student assistants. With our developed method, we are able to
represent the study data in a clinical concept-based platform, which means less
integration effort for access and processing of research and clinical data. Some
minor difficulties occurred during the process. All in all, adapting routine
tools, like the EHR platform, seems to be convenient to deal with research data.
PMID- 28423774
TI - The 'PEARL' Data Warehouse: Initial Challenges Faced with Semantic and Syntactic
Interoperability.
AB - Data about patients are available from diverse sources, including those routinely
collected as individuals interact with service providers, and those provided
directly by individuals through surveys. Linking these data can lead to a more
complete picture about the individual, to inform either care decision making or
research investigations. However, post-linkage, differences in data recording
systems and formats present barriers to achieving these aims. This paper
describes an approach to combine linked GP records with study observations, and
reports initial challenges related to semantic and syntactic interoperability
issues.
PMID- 28423775
TI - Combining Different Privacy-Preserving Record Linkage Methods for Hospital
Admission Data.
AB - Record linkage (RL) is the process of identifying pairs of records that
correspond to the same entity, for example the same patient. The basic approach
assigns to each pair of records a similarity weight, and then determines a
certain threshold, above which the two records are considered to be a match.
Three different RL methods were applied under privacy-preserving conditions on
hospital admission data: deterministic RL (DRL), probabilistic RL (PRL), and
Bloom filters. The patient characteristics like names were one-way encrypted
(DRL, PRL) or transformed to a cryptographic longterm key (Bloom filters). Based
on one year of hospital admissions, the data set was split randomly in 30
thousand new and 1,5 million known patients. With the combination of the three RL
methods, a positive predictive value of 83 % (95 %-confidence interval 65 %-94 %)
was attained. Thus, the application of the presented combination of RL-methods
seem to be suited for other applications of population-based research.
PMID- 28423776
TI - Application of Correspondence Analysis to Graphically Investigate Associations
Between Foods and Eating Locations.
AB - This paper presents the application of correspondence analysis (CA) for
investigating associations using confidence regions (CRs) with a focus on
facilitating mining the data and hypothesis generation. We study the relationship
between locations and "less-healthy" food consumption by UK teenagers. CA allows
for a quick visual inspection of the various association structures that exist
between the categories of cross-classified variables in large datasets derived
with varying study designs. The hypotheses generated by the visual display can
then be independently tested using suitable regression models. CA makes use of
readily available software tools and of robust statistical tests amenable to
interpretation.
PMID- 28423777
TI - Data Driven Quality Improvement of Health Professions Education: Design and
Development of CLUE - An Interactive Curriculum Data Visualization Tool.
AB - Curriculum Mapping and dynamic visualization is quickly becoming an integral
aspect of quality improvement in support of innovations which drive curriculum
quality assurance processes in medical education. CLUE (Curriculum Explorer) a
highly interactive, engaging and independent platform was developed to support
curriculum transparency, enhance student engagement, and enable granular search
and display. Reflecting a design based approach to meet the needs of the school's
varied stakeholders, CLUE employs an iterative and reflective approach to drive
the evolution of its platform, as it seeks to accommodate the ever-changing needs
of our stakeholders in the fast pace world of medicine and medical education
today. CLUE exists independent of institutional systems and in this way, is
uniquely positioned to deliver a data driven quality improvement resource, easily
adaptable for use by any member of our health care professions.
PMID- 28423778
TI - Developing Healthcare Data Analytics APPs with Open Data Science Tools.
AB - Recent advances in big data analytics provide more flexible, efficient, and open
tools for researchers to gain insight from healthcare data. Whilst many tools
require researchers to develop programs with programming languages like Python, R
and so on, which is not a skill set grasped by many researchers in the healthcare
data analytics area. To make data science more approachable, we explored existing
tools and developed a practice that can help data scientists convert existing
analytics pipelines to user-friendly analytics APPs with rich interactions and
features of real-time analysis. With this practice, data scientists can develop
customized analytics pipelines as APPs in Jupyter Notebook and disseminate them
to other researchers easily, and researchers can benefit from the shared notebook
to perform analysis tasks or reproduce research results much more easily.
PMID- 28423779
TI - Fast and Efficient Feature Engineering for Multi-Cohort Analysis of EHR Data.
AB - We present a framework for feature engineering, tailored for longitudinal
structured data, such as electronic health records (EHRs). To fast-track feature
engineering and extraction, the framework combines general-use plug-in
extractors, a multi-cohort management mechanism, and modular memoization. Using
this framework, we rapidly extracted thousands of features from diverse and large
healthcare data sources in multiple projects.
PMID- 28423780
TI - Development and Evaluation of a Case-Based Retrieval Service.
AB - Identifying similar patients might greatly facilitate the treatment of a given
patient, enabling to observe the response and outcome to a particular treatment.
Case-based retrieval services dealing with natural language processing are of
major importance to deal with the significant amount of unstructured clinical
data. In this paper, we present the development and evaluation of a case-based
retrieval (CBR) service tested on a collection of Italian pediatric cardiology
cases. Cases are indexed and a search engine is proposed. Search functionalities,
such as interactive MeSH normalization and relevance feedback, are proposed.
While the qualitative evaluation aims to provide feedback and recommendations,
the quantitative evaluation enables to estimate the precision of the system. In
more than half of the cases and for up to two thirds of them, the system is able
to suggest a similar episode of care at first rank. With an improvement of the
feedback relevance strategy, we can expect an improvement of the precision. The
CBR can be expanded to multilingual EHR and other fields.
PMID- 28423781
TI - Learning Differentially Expressed Gene Pairs in Microarray Data.
AB - To identify differentially expressed genes (DEGs) in analysis of microarray data,
a majority of existing filter methods rank gene individually. Such a paradigm
could overlook the genes with trivial individual discriminant powers but
significant powers of discrimination in their combinations. This paper proposed
an impurity metric in which the number of split intervals for each feature is
considered as a parameter to be optimized for gaining maximal discrimination. The
proposed method was first evaluated by applying to a synthesized noisy
rectangular grid dataset, in which the significant feature pair which forms a
rectangular grid pattern was successfully recognized. Furthermore, applying to
the identification of DEGs on colon microarray data, the proposed method
demonstrated that it could become an alternative to Fisher's test for the
prescreening of genes which led to better performance of the SVM-RFE method.
PMID- 28423782
TI - Developing a Manually Annotated Corpus of Clinical Letters for Breast Cancer
Patients on Routine Follow-Up.
AB - This paper introduces the annotation schema and annotation process for a corpus
of clinical letters describing the disease course and treatment of oestrogen
receptor positive breast cancer patients, after completion of primary surgery and
radiotherapy treatment. Concepts related to therapy, clinical signs, and
recurrence, as well as relationships linking these, are identified and annotated
in 200 letters. This corpus will provide the basis for development of natural
language processing tools for automatic extraction of key clinical factors from
such letters.
PMID- 28423783
TI - Automated Diagnosis Coding with Combined Text Representations.
AB - Automated diagnosis coding can be provided efficiently by learning predictive
models from historical data; however, discriminating between thousands of codes
while allowing a variable number of codes to be assigned is extremely difficult.
Here, we explore various text representations and classification models for
assigning ICD-9 codes to discharge summaries in MIMIC-III. It is shown that the
relative effectiveness of the investigated representations depends on the
frequency of the diagnosis code under consideration and that the best performance
is obtained by combining models built using different representations.
PMID- 28423784
TI - Using Statistics and Data Mining Approaches to Analyze Male Sexual Behaviors and
Use of Erectile Dysfunction Drugs Based on Large Questionnaire Data.
AB - The prevalence of erectile dysfunction (ED) has been extensively studied
worldwide. Erectile dysfunction drugs has shown great efficacy in preventing male
erectile dysfunction. In order to help doctors know drug taken preference of
patients and better prescribe, it is crucial to analyze who actually take
erectile dysfunction drugs and the relation between sexual behaviors and drug
use. Existing clinical studies usually used descriptive statistics and regression
analysis based on small volume of data. In this paper, based on big volume of
data (48,630 questionnaires), we use data mining approaches besides statistics
and regression analysis to comprehensively analyze the relation between male
sexual behaviors and use of erectile dysfunction drugs for unravelling the
characteristic of patients who take erectile dysfunction drugs. We firstly
analyze the impact of multiple sexual behavior factors on whether to use the
erectile dysfunction drugs. Then, we explore to mine the Decision Rules for
Stratification to discover patients who are more likely to take drugs. Based on
the decision rules, the patients can be partitioned into four potential groups
for use of erectile dysfunction: high potential group, intermediate potential-1
group, intermediate potential-2 group and low potential group. Experimental
results show 1) the sexual behavior factors, erectile hardness and time length to
prepare (how long to prepares for sexual behaviors ahead of time), have bigger
impacts both in correlation analysis and potential drug taking patients
discovering; 2) odds ratio between patients identified as low potential and high
potential was 6.098 (95% confidence interval, 5.159-7.209) with statistically
significant differences in taking drug potential detected between all potential
groups.
PMID- 28423785
TI - Automated Identification of National Health Survey Research Topics in the
Academic Literature.
AB - National health surveys are routinely conducted to provide value data about a
country's health status and the health services being consumed by the population.
This information is used for surveillance, research, and the planning of
healthcare services at local and national levels. Although these national health
surveys are viewed as important resources for public and population health, there
is limited information as to the type of research being conducted with these
surveys. This study investigates, through the use of automated text data mining,
an approach to identify and collate the type of academic literature being
published using national health surveys.
PMID- 28423786
TI - Prevalence Estimation of Protected Health Information in Swedish Clinical Text.
AB - Obscuring protected health information (PHI) in the clinical text of health
records facilitates the secondary use of healthcare data in a privacy-preserving
manner. Although automatic de-identification of clinical text using machine
learning holds much promise, little is known about the relative prevalence of PHI
in different types of clinical text and whether there is a need for domain
adaptation when learning predictive models from one particular domain and
applying it to another. In this study, we address these questions by training a
predictive model and using it to estimate the prevalence of PHI in clinical text
written (1) in different clinical specialties, (2) in different types of notes
(i.e., under different headings), and (3) by persons in different professional
roles. It is demonstrated that the overall PHI density is 1.57%; however,
substantial differences exist across domains.
PMID- 28423787
TI - IT Infrastructure of an Oncological Trial Where Xenografts Inform Individual
Second Line Treatment Decision.
AB - Translational clinical research is often characterized by a unidirectional
information flow from clinical to molecular data by using phenotypes to elucidate
molecular disease processes. Here we present the RESIST study which uses
xenograft information for individual treatment decisions after resistance to a
specific anticancer treatment establishing a bidirectional information flow
between patient and molecular biology. The paper discusses the specific
challenges related to the IT infrastructure for such bidirectional translational
projects and proposes solutions. A specific focus is the safeguarding genomic
privacy.
PMID- 28423788
TI - Medical and Healthcare Curriculum Exploratory Analysis.
AB - In the recent years, medical and healthcare higher education institutions compile
their curricula in different ways in order to cover all necessary topics and
sections that the students will need to go through to success in their future
clinical practice. A medical and healthcare curriculum consists of many
descriptive parameters, which define statements of what, when, and how students
will learn in the course of their studies. For the purpose of understanding a
complicated medical and healthcare curriculum structure, we have developed a web
oriented platform for curriculum management covering in detail formal metadata
specifications in accordance with the approved pedagogical background, namely
outcome-based approach. Our platform provides a rich database that can be used
for innovative detailed educational data analysis. In this contribution we would
like to present how we used a proven process model as a way of increasing
accuracy in solving individual analytical tasks with the available data.
Moreover, we introduce an innovative approach on how to explore a dataset in
accordance with the selected methodology. The achieved results from the selected
analytical issues are presented here in clear visual interpretations in an
attempt to visually describe the entire medical and healthcare curriculum.
PMID- 28423789
TI - Using Electronic Health Records to Assess Depression and Cancer Comorbidities.
AB - Comorbid diseases are an important concern in oncology since they can affect the
choice and effectiveness of treatment. What is particularly relevant is the fact
that the diagnosis of depression in cancer patients has an important impact on
the quality of life of these patients. Although there is no consensus about a
specific relationship of depression with certain cancer types, some authors have
proposed that depression constitutes a risk factor for cancer. The objective of
this study is to identify the presence of comorbidities in a massive EHR system,
between depression and the 10 most common cancers in women and men and to
determine if there is a preferred temporal ordering in the co-occurrence of these
diseases. All the cancers studied showed a significant co-occurrence with
depression, more specifically, twice more frequent than what could be expected by
chance. A preferred directionality was identified between some of the comorbid
diseases, such as breast cancer followed by depression, and depression followed
by either stomach cancer, colorectal cancer or lung cancer. Future work will
address other potential factors that have an influence on the likelihood of
suffering from depression in patients with cancer, such as drug therapies
received, exposure to substance of abuse or other comorbidities.
PMID- 28423790
TI - Improving Terminology Mapping in Clinical Text with Context-Sensitive Spelling
Correction.
AB - The mapping of unstructured clinical text to an ontology facilitates meaningful
secondary use of health records but is non-trivial due to lexical variation and
the abundance of misspellings in hurriedly produced notes. Here, we apply several
spelling correction methods to Swedish medical text and evaluate their impact on
SNOMED CT mapping; first in a controlled evaluation using medical literature text
with induced errors, followed by a partial evaluation on clinical notes. It is
shown that the best-performing method is context-sensitive, taking into account
trigram frequencies and utilizing a corpus-based dictionary.
PMID- 28423791
TI - Medical Text Classification Using Convolutional Neural Networks.
AB - We present an approach to automatically classify clinical text at a sentence
level. We are using deep convolutional neural networks to represent complex
features. We train the network on a dataset providing a broad categorization of
health information. Through a detailed evaluation, we demonstrate that our method
outperforms several approaches widely used in natural language processing tasks
by about 15%.
PMID- 28423792
TI - Acronym Disambiguation in Spanish Electronic Health Narratives Using Machine
Learning Techniques.
AB - Electronic Health Records (EHRs) are now being massively used in hospitals what
has motivated current developments of new methods to process clinical narratives
(unstructured data) making it possible to perform context-based searches. Current
approaches to process the unstructured texts in EHRs are based in applying text
mining or natural language processing (NLP) techniques over the data. In
particular Named Entity Recognition (NER) is of paramount importance to retrieve
specific biomedical concepts from the text providing the semantic type of the
concept retrieved. However, it is very common that clinical notes contain lots of
acronyms that cannot be identified by NER processes and even if they are
identified, an acronym may correspond to several meanings, so disambiguation of
the found term is needed. In this work we provide an approach to perform acronym
disambiguation in Spanish EHR using machine learning techniques.
PMID- 28423793
TI - Automated Classification of Semi-Structured Pathology Reports into ICD-O Using
SVM in Portuguese.
AB - Pathology reports are a main source of information regarding cancer diagnosis and
are commonly written following semi-structured templates that include tumour
localisation and behaviour. In this work, we evaluated the efficiency of support
vector machines (SVMs) to classify pathology reports written in Portuguese into
the International Classification of Diseases for Oncology (ICD-O), a biaxial
classification of cancer topography and morphology. A partnership program with
the Brazilian hospital A.C. Camargo Cancer Center provided anonymised pathology
reports and structured data from 94,980 patients used for training and
validation. We employed SVMs with tf-idf weighting scheme in a bag-of-words
approach and report F1 score of 0.82 for 18 sites and 0.73 for 49 morphology
classes. With the largest dataset ever used in such a task, our work provides
reliable estimates for the classification of pathology reports in Portuguese and
agrees with a few similar studies published in the same kind of data in other
languages.
PMID- 28423794
TI - Informative Observation in Health Data: Association of Past Level and Trend with
Time to Next Measurement.
AB - In routine health data, risk factors and biomarkers are typically measured
irregularly in time, with the frequency of their measurement depending on a range
of factors - for example, sicker patients are measured more often. This is termed
informative observation. Failure to account for this in subsequent modelling can
lead to bias. Here, we illustrate this issue using body mass index measurements
taken on patients with type 2 diabetes in Salford, UK. We modelled the
observation process (time to next measurement) as a recurrent event Cox model,
and studied whether previous measurements in BMI, and trends in the BMI, were
associated with changes in the frequency of measurement. Interestingly, we found
that increasing BMI led to a lower propensity for future measurements. More
broadly, this illustrates the need and opportunity to develop and apply models
that account for, and exploit, informative observation.
PMID- 28423795
TI - Multivariate and Longitudinal Health System Indicators.
AB - Within population health information systems, indicators are commonly presented
as independent, cross-sectional measures, neglecting the multivariate,
longitudinal nature of disease progression, health care use, and profiles of
performance. We use administrative claims data of Montreal, Canada to identify
patterns across indicators and over time in chronic obstructive pulmonary disease
patients. We first cluster regions based on four health service indicators. Our
second approach discovers individual-level trajectories based on a hidden Markov
model using the same four indicators. Both approaches offer additional insights
by facilitating the discovery and interpretation of indicators, such as a dual
interpretation of low use of general practitioner services. These approaches to
the analysis and visualization of health indicators can provide a foundation for
information displays that will help decision makers identify areas of concern,
predict future disease burden, and implement appropriate policies.
PMID- 28423796
TI - Personalized Guideline-Based Treatment Recommendations Using Natural Language
Processing Techniques.
AB - Clinical guidelines and clinical pathways are accepted and proven instruments for
quality assurance and process optimization. Today, electronic representation of
clinical guidelines exists as unstructured text, but is not well-integrated with
patient-specific information from electronic health records. Consequently,
generic content of the clinical guidelines is accessible, but it is not possible
to visualize the position of the patient on the clinical pathway, decision
support cannot be provided by personalized guidelines for the next treatment
step. The Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT)
provides common reference terminology as well as the semantic link for combining
the pathways and the patient-specific information. This paper proposes a model
based approach to support the development of guideline-compliant pathways
combined with patient-specific structured and unstructured information using
SNOMED CT. To identify SNOMED CT concepts, a software was developed to extract
SNOMED CT codes out of structured and unstructured German data to map these with
clinical pathways annotated in accordance with the systematized nomenclature.
PMID- 28423797
TI - HTP-NLP: A New NLP System for High Throughput Phenotyping.
AB - Secondary use of clinical data for research requires a method to quickly process
the data so that researchers can quickly extract cohorts. We present two advances
in the High Throughput Phenotyping NLP system which support the aim of truly high
throughput processing of clinical data, inspired by a characterization of the
linguistic properties of such data. Semantic indexing to store and generalize
partially-processed results and the use of compositional expressions for
ungrammatical text are discussed, along with a set of initial timing results for
the system.
PMID- 28423799
TI - Global eHealth, Social Business and Citizen Engagement.
AB - The UNSW WHO Collaborating Centre (WHOCC) in eHealth was established in 2013. Its
designated activities are: mHealth and evidence-based evaluation, including use
case analyses. The UNSW Yunus Social Business Health Hub (YSBHH), established in
2015 to build on the Yunus Centre/Grameen Bank eHealth initiatives, added social
business and community participation dimensions to the UNSW global eHealth
program. The Grameen Bank is a social business built around microcredit, which
are small loans to poor people to enable them to "produce something, sell
something, earn something to develop self-reliance and a life of dignity". The
vision revolves around global partnerships for development, Millennium
Development Goals (MDGs) and Sustainable Development Goals (SDGs). The scope
includes mHealth implementation and evaluation in the context of the Internet of
Things (IoT), with a growing focus on social business and citizen engagement
approaches. This paper summarises a critical case study of the UNSW WHOCC
(eHealth) designated activities in collaboration with Bangladesh institutions
(International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDRB) and
Yunus Centre). Issues and challenges are highlighted.
PMID- 28423800
TI - Project PEACH at UCLH: Student Projects in Healthcare Computing.
AB - A collaboration between clinicians at UCLH and the Dept of Computer Science at
UCL is giving students of computer science the opportunity to undertake real
healthcare computing projects as part of their education. This is enabling the
creation of a significant research computing platform within the Trust, based on
open source components and hosted in the cloud, while providing a large group of
students with experience of the specific challenges of health IT.
PMID- 28423801
TI - Monitoring of Students' Interaction in Online Learning Settings by Structural
Network Analysis and Indicators.
AB - Learning as a constructive process works best in interaction with other learners.
Support of social interaction processes is a particular challenge within online
learning settings due to the spatial and temporal distribution of participants.
It should thus be carefully monitored. We present structural network analysis and
related indicators to analyse and visualize interaction patterns of participants
in online learning settings. We validate this approach in two online courses and
show how the visualization helps to monitor interaction and to identify activity
profiles of learners. Structural network analysis is a feasible approach for an
analysis of the intensity and direction of interaction in online learning
settings.
PMID- 28423802
TI - A Lens for Evaluating Genetic Information Governance Models: Balancing Equity,
Efficiency and Sustainability.
AB - This paper draws from the literature on collective action and the governance of
the commons to address the governance of genetic data on variants of specific
genes. Specifically, the data arrangements under study relate to the BRCA genes
(BRCA1 and BRCA2) which are linked to breast and ovarian cancer. These data are
stored in global genetic data repositories and accessed by researchers and
clinicians, from both public and private institutions. The current BRCA data
arrangements are fragmented and politicized as there are multiple tensions around
data ownership and sharing. Three key principles are proposed for forming and
evaluating data governance arrangements in the field. These principles are:
equity, efficiency and sustainability.
PMID- 28423803
TI - Business Rules to Improve Secondary Data Use of Electronic Healthcare Systems.
AB - The 'fit for purpose' paradigm used for data quality assessment in electronic
healthcare record (EHR) systems is not so fit when assessed in the light of
secondary data use. An analysis of the difficulties encountered in trying to use
existing EHR data for cohort identification for prospective clinical trials and
retrograde data analytics, revealed the root causes to fall in three categories:
(1) issues in workflow and data registration, (2) preventable inadequacies in
software configuration and personalization and (3) software development issues on
the side of the vendor. By reviewing secondary data use requirements and
formulating value adding business rules, development and data collection
practices can be steered towards greater value in secondary data consumption.
PMID- 28423804
TI - Facilitators and Barriers of Electronic Health Record Patient Portal Adoption by
Older Adults: A Literature Study.
AB - Patient portal usage by older adults, patients aged 50 years old and above, is
intended to improve their access and quality of care. Acceptance of patient
portals by this target group is low. This paper discusses the results of a
literature review to determine the facilitators and barriers that drive or
inhibit older patients to adopt patient portals. Articles were included when they
described an acceptance, adoption or usability evaluation study of a patient
portal. From a total of 245 potentially relevant articles, 8 articles were
finally included. We used the Unified Theory of Acceptance and Use of Technology
(UTAUT) as a classification model to analyze factors influencing older adults'
acceptance of patient portals. Main facilitators for acceptance were 'performance
expectancy' and 'voluntariness of use' related to a higher level of education and
experienced health. Main barriers were limited health literacy and motivation
related to involuntariness to use a patient portal. Poor facilitation conditions
(limited technology access and no prior knowledge on existence of a patient
portal) hampered access to a portal. More thorough insight into the latter is
needed to improve the reach and effectiveness of patient portals among older
patients.
PMID- 28423805
TI - Preventing Unintended Disclosure of Personally Identifiable Data Following
Anonymisation.
AB - Errors and anomalies during the capture and processing of health data have the
potential to place personally identifiable values into attributes of a dataset
that are expected to contain non-identifiable values. Anonymisation focuses on
those attributes that have been judged to enable identification of individuals.
Attributes that are judged to contain non-identifiable values are not considered,
but may be included in datasets that are shared by organisations. Consequently,
organisations are at risk of sharing datasets that unintendedly disclose
personally identifiable values through these attributes. This would have ethical
and legal implications for organisations and privacy implications for individuals
whose personally identifiable values are disclosed. In this paper, we formulate
the problem of unintended disclosure following anonymisation, describe the
necessary steps to address this problem, and discuss some key challenges to
applying these steps in practice.
PMID- 28423806
TI - Protecting Privacy of Genomic Information.
AB - The ISO/IEC committee in charge of standardizing the well-known MPEG audiovisual
standards has launched, in cooperation with the ISO committee on Biotechnology, a
new activity for efficient compressed storage and transmission of genomic
information. The paper presents proposals for adding privacy and security to such
in-progress standards.
PMID- 28423807
TI - Clinical Data Warehouse Watermarking: Impact on Syndromic Measure.
AB - Watermarking appears as a promising tool for the traceability of shared medical
databases as it allows hiding the traceability information into the database
itself. However, it is necessary to ensure that the distortion resulting from
this process does not hinder subsequent data analysis. In this paper, we present
the preliminary results of a study on the impact of watermarking in the
estimation of flu activities. These results show that flu epidemics periods can
be estimated without significant perturbation even when considering a moderate
watermark distortion.
PMID- 28423808
TI - Security Policy and Infrastructure in the Context of a Multi-Centeric Information
System Dedicated to Autism Spectrum Disorder.
AB - Autism spectrum disorders (ASD) are complex neuro-developmental disorders
affecting children in their early age. The diagnosis of ASD relies on
multidisciplinary investigations, in psychiatry, neurology, genetics,
electrophysiology, neuro-imagery, audiology and ophthalmology. In order to
support clinicians, researchers and public health decision makers, we designed an
information system dedicated to ASD, called TEDIS. TEDIS was designed to manage
systematic, exhaustive and continuous multi-centric patient data collection via
secured Internet connections. In this paper, we present the security policy and
security infrastructure we developed to protect ASD' patients' clinical data and
patients' privacy. We tested our system on 359 ASD patient records in a local
secured intranet environment and showed that the security system is functional,
with a consistent, transparent and safe encrypting-decrypting behavior. It is
ready for deployment in the nine ASD expert assessment centers in the Ile de
France district.
PMID- 28423809
TI - Use of a Nationwide Personally Controlled Electronic Health Record by Healthcare
Professionals and Patients: A Case Study with the French DMP.
AB - If the wide adoption of electronic health records (EHRs) is necessary to address
health information sharing and care coordination issues, it is not sufficient. In
order to address health information sharing, some countries, among which, France,
have implemented a centralized framework with "new" nationwide care records. The
French DMP is a centralized, nationally shared, electronic medical record,
created according to the opt-in model. More than five years after the launching
of the DMP project, DMPs have been created for 1.5% of the target population,
which demonstrates the poor adoption of the tool by healthcare professionals.
Among the 583,997 existing DMPs in June 2016, 41% were empty, and 24% of non
empty DMPs were actually accessed. If these "active" DMPs were equally accessed
by both healthcare professionals and patients, patients accessed DMP documents
four times more than healthcare professionals.
PMID- 28423810
TI - Use and Adaptation of Open Source Software for Capacity Building to Strengthen
Health Research in Low- and Middle-Income Countries.
AB - Health research capacity strengthening is of importance to reach health goals.
The ARCADE projects' aim was to strengthen health research across Africa and Asia
using innovative educational technologies. In the four years of the EU funded
projects, challenges also of technical nature were identified. This article
reports on a study conducted within the ARCADE projects. The study focused on
addressing challenges of video conferencing in resource constrained settings and
was conducted using action research. As a result, a plugin for the open source
video conferencing system minisip was implemented and evaluated. The study showed
that both the audio and video streams could be improved by the introduced plugin,
which addressed one technical challenge.
PMID- 28423811
TI - Connecting the Links: Narratives, Simulations and Serious Games in Prehospital
Training.
AB - Due to rapid and substantial changes in the health sector, collaboration and
supporting technologies get more into focus. Changes in education and training
are also required. Simulations and serious games (SSG) are often advocated as
promising technologies supporting training of many and in the same manner, or
increasing the skills necessary to deal with new, dangerous, complex or
unexpected situations. The aim of this paper is to illustrate and discuss
resources needed for planning and performing collaborative contextual training
scenarios. Based on a practical study involving prehospital nurses and different
simulator technologies the often-recurring activity chains in prehospital
training were trained. This paper exemplifies the benefit of using narratives and
SSGs for contextual training contributing to higher user experiences. The
benefits of using simulation technologies aligned by processes can be easier
defined by narratives from practitioners. While processes help to define more
efficient and effective training, narratives and SSGs are beneficial to design
scenarios with clues for higher user experiences. By discussing illustrative
examples, the paper contributes to better understanding of how to plan simulation
technology rich training scenarios.
PMID- 28423812
TI - Designing an E-Learning Platform for Postoperative Arthroplasty Adverse Events.
AB - This paper presents a mobile software application development for e-learning
based on the adverse events data within the field of arthroplasty. The
application aims at providing a learning platform for physicians, patients, and
medical students. Design of user interface aims to meet requirements of several
user groups concerned with the adverse events of the knee and hip implants.
Besides the clinical patient data, the platform wants to include even electronic
patient data as a result of self-monitoring. Two different modules were created,
one for medical staff and one for patients, both divided into the knee and hip
areas. Knowledge is represented in forms of statistics, treatment options, and
detailed, actual adverse event reports. Patients are given a choice of
recommendation for two main situations: 'about your diagnosis', and 'what if you
get a problem' as advice and guidance during the postoperative rehabilitation.
Expert evaluation resulted in acceptance of the concept and provided feedback
ideas. The patient evaluation has also been positive. Implementation will mean
that a high-fidelity prototype will be developed and tested in larger user groups
(medical staff, patients).
PMID- 28423813
TI - Understanding the Context of Learning in an Online Social Network for Health
Professionals' Informal Learning.
AB - Online social networks (OSN) enable health professionals to learn informally, for
example by sharing medical knowledge, or discussing practice management
challenges and clinical issues. Understanding the learning context in OSN is
necessary to get a complete picture of the learning process, in order to better
support this type of learning. This study proposes critical contextual factors
for understanding the learning context in OSN for health professionals, and
demonstrates how these contextual factors can be used to analyse the learning
context in a designated online learning environment for health professionals.
PMID- 28423814
TI - Ubiquitous Adoption of Innovative and Supportive Information and Communications
Technology Across Health and Social Care Needs Education for Clinicians.
AB - The paper presents the development, use and evaluation of an on-line
undergraduate module delivering an academic-led programme of eHealth learning
within nursing, midwifery, allied health professional and social work courses.
The health information technology competency frameworks are explored along with
an overview of the resulting module. The need for an academically led module will
be made along with a description of the management required to maintain validity
of content materials. A review of student evaluations will be presented. In
conclusion the positive change in attitude and understanding of academic staff
members towards health information technology through the inclusion of the module
across all of the undergraduate courses will be explored.
PMID- 28423815
TI - Mobile Medical Apps and mHealth Devices: A Framework to Build Medical Apps and
mHealth Devices in an Ethical Manner to Promote Safer Use - A Literature Review.
AB - This paper presents a preliminary literature review in the area of ethics in the
development of Mobile Medical Apps and mHealth. The review included both direct
health apps and also apps marketed under the area of well-being in addition to
mHealth devices. The following words and combinations of them were used to carry
out the search for publications, mHealth, Apps, Ethics. The search engines used
were Google Scholar, and PubMed. The paper is restricted to publications since
2012. The total number of papers found was 1,920 of which 84 were reviewed. The
reason for so few being reviewed was that the majority only considered security.
The search revealed many papers dealing with security for all types of apps and
mHealth devices but there are very few papers dealing with the ethical issues
related to Apps or mHealth devices in the area. It is noted however that the
number of apps is increasing in number exponentially and therefore it is argued
that it is necessary to pay attention to the ethical aspects. There are now
estimated to be 165,000 apps available in this area. How ethics are addressed in
health and well-being apps is important as they can have an effect on the health
of the individual using them. In a similar way, the need for addressing ethical
issues for development of well-being apps is evident. In a study [1] it was noted
that even though Electronic Health Record (EHR) was the highest ranked tablet
related task only one third of clinicians said that EHR was optimized for
smartphones. When apps are integrated with the EHR they fully optimize
productivity. In the same study the significant challenges identified included
the method of evaluation and selection of mobile health solutions in order to
ensure that clinical outcomes, care and efficiency are included. Security is
mentioned but again wider ethical issues were not a consideration. From the
literature review it is clear that there is a need for guidelines for how
developers of medical ad well-being apps and mHealth devices should address
ethical issues during development, and the generation of these guidelines is the
subject of ongoing research by the authors.
PMID- 28423816
TI - A Method for Co-Designing Theory-Based Behaviour Change Systems for Health
Promotion.
AB - A methodology was defined and developed for designing theory-based behaviour
change systems for health promotion that can be tailored to the individual.
Theories from two research fields were combined with a participatory action
research methodology. Two case studies applying the methodology were conducted.
During and between group sessions the participants created material and designs
following the behaviour change strategy themes, which were discussed, analysed
and transformed into a design of a behaviour change system. Theories in
behavioural change and persuasive technology guided the data collection, data
analyses, and the design of a behaviour change system. The methodology has strong
emphasis on the target group's participation in the design process. The different
aspects brought forward related to behaviour change strategies defined in
literature on persuasive technology, and the dynamics of these are associated to
needs and motivation defined in literature on behaviour change. It was concluded
that the methodology aids the integration of theories into a participatory action
research design process, and aids the analyses and motivations of design choices.
PMID- 28423817
TI - Persona Development and Educational Needs to Support Informal Caregivers.
AB - Informal caregivers are playing an increasing role in community based care
delivery. Research is needed that looks at the educational needs of informal
caregivers as a precursor to HIT design to support community care delivery. A
challenge is informal caregivers have very diverse educational needs. Personas
are an approach to describe user characteristics as part of systems design and
this approach could be used to understand and categorize the various educational
needs of informal caregivers. This paper addresses this research need and
provides a method for persona development and the identification of educational
needs for informal caregivers.
PMID- 28423818
TI - An Approach for Enhancing Adoption, Use and Utility of Shared Digital Health
Records in Rural Australian Communities.
AB - Internationally, shared digital health records are considered an important
addition to improving modern health care provision. Australia launched its
version, My Health Record (MyHR), in 2012 but has experienced low adoption and
challenges in practical implementation and evaluation. Individuals living with
complex and chronic conditions in rural and remote communities often experience
challenges in obtaining equitable access to health care provision. They are also
supposed to face additional barriers to adopting and using eHealth services. This
paper reports on research investigating adoption, use and utility of MyHR, in
rural remote Australian community settings. Based on this research an approach
for improving national roll out of MyHR is presented. The approach highlights a
means to understand and engage communities with complex care needs, to support
their adoption and use of digital tools. It also draws attention to holistic
methods for evaluating and assessing impact at individual, community and health
care provision levels.
PMID- 28423819
TI - Exploring Innovation Capabilities of Hospital CIOs: An Empirical Assessment.
AB - Hospital CIOs play a central role in the adoption of innovative health IT. Until
now, it remained unclear which particular conditions constitute their capability
to innovate in terms of intrapersonal as well as organisational factors. An
inventory of 20 items was developed to capture these conditions and examined by
analysing data obtained from 164 German hospital CIOs. Principal component
analysis resulted in three internally consistent components that constitute large
portions of the CIOs innovation capability: organisational innovation culture,
entrepreneurship personality and openness towards users. Results were used to
build composite indicators that allow further evaluations.
PMID- 28423820
TI - The Invisibility of Disadvantage: Why Do We Not Notice?
AB - Personal health records (PHRs) offer tantalising benefits for patients and
healthcare providers, including improvements in patient-provider communication,
patient empowerment, and access to data and information. A suspicion that
disadvantaged patients are less likely to use or benefit from PHRs stimulated a
research agenda that included: (a) a literature review; and (b) empirical
analysis of eight years' hospital admission and discharge data linked to measures
of patient social disadvantage. The results demonstrated an association between
disadvantage, increased use of public hospital services and barriers to PHR use.
These findings may appear self-evident, but dramatically highlight how
disadvantaged patients continue to be overlooked in many e-health design
processes, and are rarely a focus of user centred design. The paper concludes by
briefly considering the implications of this invisibility.
PMID- 28423821
TI - Using Healthcare Work Process Modelling in Hospitals to Increase the Fit Between
the Healthcare Workflow and the Electronic Medical Record.
AB - As with other organizations, hospitals tend to promote unrealistic expectations
related to software implementaton. Quite often the real issue is a misfit between
the software and organizational factors. Our paper shows how work process
modelling within the hospital can reduce this misfit according to the vision
developped by the ergonomics and the management of information systems. This idea
is supported by two cases in two different University Hospitals in France, in
which using work process modelling lead to identification of problems and their
causes, and solutions. Modelling requires time, which may be considered costly by
senior hospital managers, but also should be considered as an investment in order
to achieve expected goals.
PMID- 28423823
TI - Reference Architecture Model Enabling Standards Interoperability.
AB - Advanced health and social services paradigms are supported by a comprehensive
set of domains managed by different scientific disciplines. Interoperability has
to evolve beyond information and communication technology (ICT) concerns,
including the real world business domains and their processes, but also the
individual context of all actors involved. So, the system must properly reflect
the environment in front and around the computer as essential and even defining
part of the health system. This paper introduces an ICT-independent system
theoretical, ontology-driven reference architecture model allowing the
representation and harmonization of all domains involved including the
transformation into an appropriate ICT design and implementation. The entire
process is completely formalized and can therefore be fully automated.
PMID- 28423824
TI - Querying Archetype-Based Electronic Health Records Using Hadoop and Dewey
Encoding of openEHR Models.
AB - Archetype-based Electronic Health Record (EHR) systems using generic reference
models from e.g. openEHR, ISO 13606 or CIMI should be easy to update and
reconfigure with new types (or versions) of data models or entries, ideally with
very limited programming or manual database tweaking. Exploratory research (e.g.
epidemiology) leading to ad-hoc querying on a population-wide scale can be a
challenge in such environments. This publication describes implementation and
test of an archetype-aware Dewey encoding optimization that can be used to
produce such systems in environments supporting relational operations, e.g. RDBMs
and distributed map-reduce frameworks like Hadoop. Initial testing was done using
a nine-node 2.2 GHz quad-core Hadoop cluster querying a dataset consisting of
targeted extracts from 4+ million real patient EHRs, query results with sub
minute response time were obtained.
PMID- 28423825
TI - HEMIC Project: Design of a Clinical Information Modelling Tool Based on ISO13972
Technical Specification.
AB - The Andalusian Health Service is the public healthcare provider for 8.302.923
inhabitants in the South Spain. This organization coordinates primary and
specialized care with an IT infrastructure composed by multiple Electronic Health
Record Systems. According to the large volume of healthcare professionals
involved, there is a need for providing a consistent management of information
through multiple locations and systems. The HEMIC project aims to address this
need developing and validating a methodology based on a software tool for
standardizing information contained within EHR systems. The developed tool has
been designed for supporting the participation of healthcare professionals the
establishment of mechanisms for information governance. This research presents
the requirements and designs for of a software tool focused on the adoption of
recognized best practice in clinical information modeling. The designed tool has
a Service Oriented Architecture that will be able to integrate terminology
servers and repositories of clinical information models as part of the modeling
process. Moreover, the defined tool organizes clinicians, IT developers and
terminology experts involved in the modeling process in three levels to promote
their coordination in the definition, specialization and validation of clinical
information models. In order to ensure the quality of the developed clinical
information models, the defined tool is based on the requirements defined in the
ISO13972 Technical Specification.
PMID- 28423826
TI - Combining Archetypes, Ontologies and Formalization Enables Automated Computation
of Quality Indicators.
AB - ArchMS is a framework that represents clinical information and knowledge using
ontologies in OWL, which facilitates semantic interoperability and thereby the
exploitation and secondary use of clinical data. However, it does not yet support
the automated assessment of quality of care. CLIF is a stepwise method to
formalize quality indicators. The method has been implemented in the CLIF tool
which supports its users in generating computable queries based on a patient data
model which can be based on archetypes. To enable the automated computation of
quality indicators using ontologies and archetypes, we tested whether ArchMS and
the CLIF tool can be integrated. We successfully automated the process of
generating SPARQL queries from quality indicators that have been formalized with
CLIF and integrated them into ArchMS. Hence, ontologies and archetypes can be
combined for the execution of formalized quality indicators.
PMID- 28423827
TI - Parallel Design of Browsing Scheme and Data Model for Multi-Level Hierarchical
Application Devoted to Management of Patient with Infectious Disease in Primary
Care.
AB - Many decision systems are based on a hierarchical approach, enriching the known
context used to finally choose the right potential action. Designing the scheme
for browsing the clinical guidelines is a task devoted to expert in infectious
diseases. Designing the data model is a task devoted to the expert in data
modeling. As a consequence, browsing scheme and data model generally differ in
terms of abstraction levels. While the browsing scheme proposes to navigate into
depth, the data model stays flat. We propose here a novel method to design in
parallel the browsing scheme and the data model so that both of them reflect the
different abstraction levels in decision process.
PMID- 28423828
TI - Preliminary Analysis of the OBO Foundry Ontologies and Their Evolution Using
OQuaRE.
AB - The biomedical community has now developed a significant number of ontologies.
The curation of biomedical ontologies is a complex task as they evolve rapidly,
being new versions regularly published. Therefore, methods to support ontology
developers in analysing and tracking the evolution of their ontologies are
needed. OQuaRE is an ontology evaluation framework based on quantitative metrics
that permits to obtain normalised scores for different ontologies. In this work,
OQuaRE has been applied to 408 versions of the eight OBO Foundry member
ontologies. The OBO Foundry member ontologies are supposed to have been built by
applying the OBO Foundry principles. Our results show that this set of ontologies
is actually following principles such as the naming convention, and that the
evolution of the OBO Foundry member ontologies is generating ontologies with
higher OQuaRE quality scores.
PMID- 28423829
TI - Ontological Realism for the Research Domain Criteria for Mental Disorders.
AB - At the heart of the Research Domain Criteria for Mental Disorders is a matrix in
which functional aspects of behavior are related to genotypic and (endo
)phenotypic research findings, and the various techniques through which they can
been observed. The matrix is work in progress. As such it currently suffers from
several shortcomings, the resolution of which, we contend, are essential to
success of NIMH's goal of fostering translational science on mental disorders.
Using well-established criteria for assessing the terminological and ontological
quality of biomedical representations we identified the major problems to be (1)
the abundant presence of terms that lack face value, (2) the absence of what the
exact nature of the represented relationships are, and (3) referential
imprecision with respect to the intended granularity of what the terms denote. We
propose to eliminate these shortcomings by resorting to definitions and formal
representations under the umbrella of Ontological Realism as they already have
been developed in the areas of mental health, anatomy and biological functions.
PMID- 28423830
TI - Bridging the Semantic Gap Between Diagnostic Histopathology and Image Analysis.
AB - With the wider acceptance of Whole Slide Images (WSI) in histopathology domain,
automatic image analysis algorithms represent a very promising solution to
support pathologist's laborious tasks during the diagnosis process, to create a
quantification-based second opinion and to enhance inter-observer agreement. In
this context, reference vocabularies and formalization of the associated
knowledge are especially needed to annotate histopathology images with labels
complying with semantic standards. In this work, we elaborate a sustainable
triptych able to bridge the gap between pathologists and image analysis
scientists. The proposed paradigm is structured along three components: i)
extracting a relevant semantic repository from the College of American
Pathologists (CAP) organ-specific Cancer Checklists and associated Protocols
(CC&P); ii) identifying imaging formalized knowledge issued from effective
histopathology imaging methods highlighted by recent Digital Pathology (DP)
contests and iii) proposing a formal representation of the imaging concepts and
functionalities issued from major biomedical imaging software (MATLAB, ITK,
ImageJ). Since the first step i) has been the object of a recent publication of
our team, this study focuses on the steps ii) and iii). Our hypothesis is that
the management of available semantic resources concerning the histopathology
imaging tasks associated with effective methods highlighted by the recent DP
challenges will facilitate the integration of WSI in clinical routine and support
new generation of DP protocols.
PMID- 28423831
TI - The BioTop Family of Upper Level Ontological Resources for Biomedicine.
AB - BioTop is a domain upper level ontology for the life sciences, based on OWL DL,
introduced ten years ago. This paper provides an update of the current state of
this resource, with a special focus on BioTop's top level, BioTopLite, which
currently contains 55 classes, 37 object properties and 247 description logics
axioms. A bridging file allows harmonising BioTopLite with the classes of Basic
Formal Ontology BFO2. The updated OWL resources are available at
http://purl.org/biotop. They build the core of several upper level ontological
artefacts including bridging ontologies to other upper level resources.
PMID- 28423832
TI - Building SNOMED CT Post-Coordinated Expressions from Annotation Groups.
AB - SNOMED CT supports post-coordination, a technique to combine clinical concepts to
ontologically define more complex concepts. This technique follows the validity
restrictions defined in the SNOMED CT Concept Model. Pre-coordinated expressions
are compositional expressions already in SNOMED CT, whereas post-coordinated
expressions extend its content. In this project we aim to evaluate the
suitability of existing pre-coordinated expressions to provide the patterns for
composing typical clinical information based on a defined list of sets of
interrelated SNOMED CT concepts. The method produces a 9.3% precision and a 95.9%
recall. As a consequence, further investigations are needed to develop heuristics
for the selection of the most meaningful matched patterns to improve the
precision.
PMID- 28423833
TI - HL7 FHIR: Ontological Reinterpretation of Medication Resources.
AB - "A solid ontology-based analysis with a rigorous formal mapping for correctness"
is one of the ten reasons why the HL7 standard Fast Healthcare Interoperability
Resources (FHIR) is advertised to be better than other standards for EHR
interoperability. In this paper, we aim at contributing to this formal analysis
by proposing an RDF representation of a subset of FHIR resources based on a
highly constrained top-level ontology and guided by the use of a set of Content
Ontology Design Patterns (Content ODPs) for representing clinical information. We
exemplify this by reinterpreting FHIR medication resources. Although a manual
task now, we foresee a possible automatic translation by using RDF shapes.
PMID- 28423834
TI - Communication of Children Symptoms in Emergency: Classification of the
Terminology.
AB - The significant part of non-urgent visits to the emergency highlight the
necessity to advise people on the actions to take according to their symptoms.
Although information sources are accessible through different channels their
content often employs medical terminologies that are difficult to understand by
laypersons. Our goal is to provide a terminology of the most common symptoms in
pediatric emergency adapted to laypersons. This terminology is organized in a
hierarchy by the mean of a card-sorting study. The resulting classification
separates the symptoms into two main categories: "accident" and "illness" that
are subdivided in 9 and 10 sub-categories. The study also revealed that some
symptoms were not understood by the participants and had to be reformulated,
confirming the importance of user-centered method. The classification resulting
from this study will be evaluated through a tree-test.
PMID- 28423835
TI - SNOMED CT as Reference Terminology in the Danish National Home Care Documentation
Standard.
AB - In Danish home care, multiple professions deliver services to citizens. FSIII is
a national home care documentation standard, where one of the goals is to share
documentation to improve coordination between these professional groups and avoid
double documentation. The aim of this study was to develop a SNOMED-CT based
navigation hierarchy to ensure that professions could preserve their
documentation practice, to help avoid double documentation, and to ensure that
the technical implementation did not require sophisticated semantic tools. The
method involved mapping of non-SNOMED-CT content to SNOMED CT, visualization of
merged graphs, identification of reference concepts, relating reference concepts
to the documentation models of each profession, and representation of the
navigation hierarchy in a reference set. The navigation hierarchy ensures that
citizen conditions appear in a relevant context, regardless of which profession
entered the data. Our approach paves the way for incremental standardization
projects, where an implementation artefact, such as the navigation hierarchy,
highlights the semantic features of SNOMED CT that can be used to reach specific
business goals; in this case, sharing data across professional groups.
PMID- 28423836
TI - Piloting a Collaborative Web-Based System for Testing ICD-11.
AB - BACKGROUND: The 11th revision of the International Classification of
Diseases (ICD-11), for the first time in ICD history, deployed web-based
collaboration of experts and ICT tools. To ensure that ICD-11 is working well, it
needs to be systematically field tested in different settings, across the world.
This will be done by means of a number of experiments. In order to support its
implementation, a web-based system (ICDfit) has been designed and developed. The
present paper illustrates the current prototype of the system and its technical
testing. METHODS: the system has been designed according to WHO requirements, and
implemented using PHP and MySQL. Then, a preliminary technical test has been
designed and run in January 2016, involving 8 users. They had to carry out double
coding, that is, coding case summaries with both ICD-10 and ICD-11, and answering
quick questions on the coding difficulty. RESULTS: the 8 users coded 632 cases
each, spending an average of 163 seconds per case. While we found an issue in the
mechanism used to record coding times, no further issues were found. CONCLUSION:
the proposed system seems to be technically adequate for supporting future ICD-11
testing.
PMID- 28423838
TI - Computable Information Governance Contracts.
AB - The risks of relinquishing control of electronic healthcare data for re-use in
research are mitigated by the use of data sharing agreements and information
governance procedures. These exist as legal, or quasi-legal, textual documents
exchanged between data owners. Their existence outside of the digital realm leads
to a situation where breaches of an agreement can only be detected and acted on
post-hoc. We introduce the design of a system of computable contracts, specified
formally, that can enforce the rules of data sharing agreements within the bounds
of electronic health care systems.
PMID- 28423837
TI - A Terminology in General Practice/Family Medicine to Represent Non-Clinical
Aspects for Various Usages: The Q-Codes.
AB - The hereby proposed terminology called "Q-Codes" can be defined as an extension
of the International Classification of Primary Care (ICPC-2). It deals with non
clinical concepts that are relevant in General Practice/Family Medicine (GP/FM).
This terminology is a good way to put an emphasis on underestimated topics such
as Teaching, Patient issues or Ethics. It aims at indexing GP/FM documents such
as congress abstracts and theses to get a more comprehensive view about the GP/FM
domain. The 182 identified Q-Codes have been very precisely defined by a college
of experts (physicians and terminologists) from twelve countries. The result is
available on the Health Terminology/Ontology Portal (http://www.hetop.org/Q) and
formatted in OWL-2 for further semantic considerations and will be used to index
the 2016 WONCA World congress communications.
PMID- 28423839
TI - A Semantic Framework for Logical Cross-Validation, Evaluation and Impact Analyses
of Population Health Interventions.
AB - Most chronic diseases are a result of a complex web of causative and correlated
factors. As a result, effective public health or clinical interventions that
intend to generate a sustainable change in these diseases most often use a
combination of strategies or programs. To optimize comparative effectiveness
evaluations and select the most efficient intervention(s), stakeholders (i.e.
public health institutions, policy-makers and advocacy groups, practitioners,
insurers, clinicians, and researchers) need access to reliable assessment
methods. Building on the theory of Evidence-Based Public Health (EBPH) we
introduce a knowledge-based framework for evaluating the consistency and
effectiveness of public health programs, interventions, and policies. We use a
semantic inference model that assists decision-makers in finding inconsistencies,
identifying selection and information biases, and with identifying confounding
and hidden dependencies in different public health programs and interventions.
The use of formal ontologies for automatic evaluation and assessment of public
health programs improves program transparency to stakeholders and decision
makers, which in turn increases buy-in and acceptance of methods, connects
multiple evaluation activities, and strengthens cost analysis.
PMID- 28423840
TI - Discovering Central Practitioners in a Medical Discussion Forum Using Semantic
Web Analytics.
AB - The aim of this paper is to investigate semantic web based methods to enrich and
transform a medical discussion forum in order to perform semantics-driven social
network analysis. We use the centrality measures as well as semantic similarity
metrics to identify the most influential practitioners within a discussion forum.
The centrality results of our approach are in line with centrality measures
produced by traditional SNA methods, thus validating the applicability of
semantic web based methods for SNA, particularly for analyzing social networks
for specialized discussion forums.
PMID- 28423841
TI - Towards an Open Infrastructure for Relating Scholarly Assets.
AB - Discovery of useful relationships between scholarly assets on the web is
challenging, both in terms generating the right metadata around the assets, and
in connecting all relevant digital entities in chain of provenance accessible to
the whole community. This paper reports the development of a framework and tools
enabling scholarly asset relationships to be expressed in a standard and open
way, illustrated with use-cases of discovering new knowledge across cohort
studies. The framework uses Research Objects for aggregation, distributed
databases for storage, and distributed ledgers for provenance. Our proposal
avoids management by a single central platform or organization, instead
leveraging the use of existing resources and platforms across natural
partnerships. Our proposed infrastructure will support a wide range of users from
system administrators to researchers.
PMID- 28423842
TI - Architecture and Initial Development of a Digital Library Platform for Computable
Knowledge Objects for Health.
AB - Throughout the world, biomedical knowledge is routinely generated and shared
through primary and secondary scientific publications. However, there is too much
latency between publication of knowledge and its routine use in practice. To
address this latency, what is actionable in scientific publications can be
encoded to make it computable. We have created a purpose-built digital library
platform to hold, manage, and share actionable, computable knowledge for health
called the Knowledge Grid Library. Here we present it with its system
architecture.
PMID- 28423843
TI - An Approach for the Support of Semantic Workflows in Electronic Health Records.
AB - With the unprecedented increase of healthcare data, technologies need to be both,
highly efficient for the meaningful utilization of accessible data and flexible
to adapt to future challenges and individual preferences. The OntoHealth system
makes use of semantic technologies to enable flexible and individual interaction
with Electronic Health Records (EHR) for physicians. This is achieved by the
execution of formally modelled clinical workflows and the composition of Semantic
Web Services (SWS). Several seamless components provide a service-oriented
structure defined by individual designed EHR-workflows. This work gives an
overview of the planned architecture and its main components. The architecture
constitutes the basis for the prototype implementation of all components. With
its highly dynamic structure based on SWS, the architecture will be able to cope
with both, the individual users' needs as well as the quick evolving healthcare
domain.
PMID- 28423844
TI - Identifying Emerging Trends in Medical Informatics: A Synthesis Approach.
AB - Medical informatics is a young and rapidly evolving field, influenced by and
impacting on many different knowledge domains. Recent contributions on scoping
the associated body of knowledge are confounded both by variations in popular use
of terminology for established areas, and by the advent of new areas without yet
established terminology. Determining the scope of a topic through online
bibliographic search filters is a well-established approach in scientific
research and has been developed as a human-directed task. Establishing the best
approach and automating the process has proved a difficult problem. This paper
explores the use of text analysis of bibliographic information using available
search engines and NVIVO text analysis tools to test the potential for dynamic
word based filters based on data mining. Results show that word searches of
abstracts are more effective than topic searches for identifying health
informatics papers, however more work is required to refine search terms to
improve generalisability. Using data mining to track changes in word use in
medical informatics journals, may make it possible to establish a more dynamic
search filter to match the evolving nature of the field of health informatics.
PMID- 28423845
TI - Appraising Healthcare Delivery Provision: A Framework to Model Business
Processes.
AB - Children are dependent on a reliable healthcare system, especially for the
delivery of care which crosses the primary/secondary care boundary. A methodology
based on UML has been developed to capture and single out meaningful parts of the
child healthcare pathways in order to facilitate comparison among 30 EU countries
within the MOCHA project. A first application of this methodology has been
reported considering asthma management as an example.
PMID- 28423846
TI - A Case Study on Sepsis Using PubMed and Deep Learning for Ontology Learning.
AB - We investigate the application of distributional semantics models for
facilitating unsupervised extraction of biomedical terms from unannotated
corpora. Term extraction is used as the first step of an ontology learning
process that aims to (semi-)automatic annotation of biomedical concepts and
relations from more than 300K PubMed titles and abstracts. We experimented with
both traditional distributional semantics methods such as Latent Semantic
Analysis (LSA) and Latent Dirichlet Allocation (LDA) as well as the neural
language models CBOW and Skip-gram from Deep Learning. The evaluation conducted
concentrates on sepsis, a major life-threatening condition, and shows that Deep
Learning models outperform LSA and LDA with much higher precision.
PMID- 28423847
TI - Acquisition of Expert/Non-Expert Vocabulary from Reformulations.
AB - Technical medical terms are complicated to be correctly understood by non
experts. Vocabulary, associating technical terms with layman expressions, can
help in increasing the readability of technical texts and their understanding.
The purpose of our work is to build this kind of vocabulary. We propose to
exploit the notion of reformulation following two methods: extraction of
abbreviations and of reformulations with specific markers. The segments
associated thanks to these methods are aligned with medical terminologies. Our
results allow to cover over 9,000 medical terms and show precision of extractions
between 0.24 and 0.98. The results and analyzed and compared with the existing
work.
PMID- 28423849
TI - Design of a Visual Interface for Comparing Antibiotics Using Rainbow Boxes.
AB - Non-optimal prescriptions of antibiotics have a negative impact on patients and
population. Clinical practice guidelines are not always followed by doctors
because the rationale of the recommendations is not always clear and can be
difficult to understand. In this paper, we propose a new approach consisting in
presenting the properties of antibiotics for allowing doctors to compare them and
choose the most appropriate one. For that, we used and extended rainbow boxes, a
new technique for overlapping set visualization. We tested our approach on 11
clinical situations related to urinary infections, and assessed the simplicity,
the interest and utility with 11 doctors. 10 of them found that this approach was
interesting and useful in clinical practice. Further studies are needed to
confirm this preliminary work.
PMID- 28423850
TI - A Method for Estimating the Risk Associated with Delaying Initial Treatment in
Breast Cancer.
AB - Over the past twenty-five years the time from diagnosis of breast cancer to the
initiation of therapy has steadily grown. In this note we present a mechanism to
give a ballpark estimate of the risk associated with delaying therapy given a
specific set of presenting patient data.
PMID- 28423851
TI - A Standardized and Data Quality Assessed Maternal-Child Care Integrated Data
Repository for Research and Monitoring of Best Practices: A Pilot Project in
Spain.
AB - We present the results of a pilot project of the Spanish Ministry of Health,
Social Services and Equality, envisaged to the development of a national
integrated data repository of maternal-child care information. Based on health
information standards and data quality assessment procedures, the developed
repository is aimed to a reliable data reuse for (1) population research and (2)
the monitoring of healthcare best practices. Data standardization was provided by
means of two main ISO 13606 archetypes (composed of 43 sub-archetypes), the first
dedicated to the delivery and birth information and the second about the infant
feeding information from delivery up to two years. Data quality was assessed by
means of a dedicated procedure on seven dimensions including completeness,
consistency, uniqueness, multi-source variability, temporal variability,
correctness and predictive value. A set of 127 best practice indicators was
defined according to international recommendations and mapped to the archetypes,
allowing their calculus using XQuery programs. As a result, a standardized and
data quality assessed integrated data respository was generated, including 7857
records from two Spanish hospitals: Hospital Virgen del Castillo, Yecla, and
Hospital 12 de Octubre, Madrid. This pilot project establishes the basis for a
reliable maternal-child care data reuse and standardized monitoring of best
practices based on the developed information and data quality standards.
PMID- 28423852
TI - Using the MRC Framework for Complex Interventions to Develop Clinical Decision
Support: A Case Study.
AB - The Medical Research Council (MRC) framework for complex interventions provides
useful guidance to assist with the development and evaluation of health
technology interventions such as decision support. In this paper we briefly
summarise a project that focused on designing a decision support intervention to
assist with the recognition, assessment and management of pain in patients with
dementia in an acute hospital setting. We reflect on our experience of using the
MRC framework to guide our study design, and highlight the importance of
considering decision support interventions as complex interventions.
PMID- 28423853
TI - Square2 - A Web Application for Data Monitoring in Epidemiological and Clinical
Studies
AB - Valid scientific inferences from epidemiological and clinical studies require
high data quality. Data generating departments therefore aim to detect data
irregularities as early as possible in order to guide quality management
processes. In addition, after the completion of data collections the obtained
data quality must be evaluated. This can be challenging in complex studies due to
a wide scope of examinations, numerous study variables, multiple examiners,
devices, and examination centers. This paper describes a Java EE web application
used to monitor and evaluate data quality in institutions with complex and
multiple studies, named Square2. It uses the Java libraries Apache MyFaces 2,
extended by BootsFaces for layout and style. RServe and REngine manage calls to R
server processes. All study data and metadata are stored in PostgreSQL. R is the
statistics backend and LaTeX is used for the generation of print ready PDF
reports. A GUI manages the entire workflow. Square2 covers all steps in the data
monitoring workflow, including the setup of studies and their structure, the
handling of metadata for data monitoring purposes, selection of variables, upload
of data, statistical analyses, and the generation as well as inspection of
quality reports. To take into account data protection issues, Square2 comprises
an extensive user rights and roles concept.
PMID- 28423854
TI - Exploring the Notion of Hazards for Health IT.
AB - Safety analysis is centred on identifying a set of hazards that form the basis of
risk assessment. In healthcare, hazards are potential sources of harm to patients
and as such the risk of these has to be assessed and managed. With the increased
reliance on Health IT systems in health and social care settings, some of these
hazards are associated with the development and use of these systems. In this
paper we examine current practices in hazard identification, focusing on how
clinicians and engineers approach this task within the Health IT safety assurance
process. We highlight certain technical and organisational challenges and discuss
approaches to improving current practices and promoting learning initiatives.
PMID- 28423855
TI - EHR Improvement Using Incident Reports.
AB - This paper discusses reactive improvement of clinical software using methods for
incident analysis. We used the "Five Whys" method because we had only descriptive
data and depended on a domain expert for the analysis. The analysis showed that
there are two major root causes for EHR software failure, and that they are
related to human and organizational errors. A main identified improvement is
allocating more resources to system maintenance and user training.
PMID- 28423856
TI - Improving Handovers Between Hospitals and Primary Care: Implementation of E
Messages and the Importance of Training.
AB - The transfer of information and responsibility for care of a patient from one
healthcare provider to another is referred to as a handover. While some handovers
are effective and achieve high quality communication, others represent a barrier
to continuity of care. To increase the patient safety, Norway decided to replace
handovers with an electronic e-message system (EMS). This paper refers to a
quantitative study of this implementation and examines the opinions of first-line
leaders and nurses (N = 108) on how organisational factors were taken into
account and how the implementation might be improved. The findings indicate that
such factors generally did not receive very much attention in the implementation
of the EMS, and less for the nurses than for the first-line leaders.
Particularly, the factor most prominently identified by both groups as warranted
improvement, was the training.
PMID- 28423857
TI - The Association Between the STOPP/START Criteria and Gastro-Intestinal Track
Bleedings in Elderly Patients.
AB - Potentially inappropriate prescribing is a common problem, especially in elderly
care. To tackle this problem, Irish medical experts have developed a list of
criteria when medication should be added or omitted based upon the patient's
physical condition and medication use, known as the STOPP and START criteria. The
STOPP and START criteria have been formulated to identify the prescribing of
potentially inappropriate medicines (PIMs) and potential prescribing omissions
(PPOs). One of the most common problems of inappropriate prescribing is gastro
intestinal track bleedings. For this purpose, nine of the 87 STOPP and START
criteria are designed to prevent this. However, the prevalence of gastro
intestinal track bleedings has not been established when these nine STOPP and
START criteria are violated. The database contained 182,000 patients belonging to
49 general practitioners in the region of Amsterdam, The Netherlands. We
estimated both the incidence of PIMs and PPOs and whether harm, in this case a
gastro-intestinal track bleeding, occurred. We found that although violation of
the nine STOPP or START criteria were possibly associated with harm (OR = 1.30),
this association was not statistically significant (p = 0.323). Searching for
evidence for harm informs decision support design aimed at improving quality of
medication prescription as it prioritizes the many suggested criteria based on
their relevance.
PMID- 28423858
TI - Needles in a Haystack: Screening and Healthcare System Evidence for Homelessness.
AB - Effectiveness of screening for homelessness in a large healthcare system was
evaluated in terms of successfully referring and connecting patients with
appropriate prevention or intervention services. Screening and healthcare
services data from nearly 6 million U.S. military veterans were analyzed.
Veterans either screened positive for current or risk of housing instability, or
negative for both. Current living situation was used to validate results of
screening. Administrative evidence for homelessness-related services was
significantly higher among positive-screen veterans who accepted a referral for
services compared to those who declined. Screening for current or risk of
homelessness led to earlier identification, which led to earlier and more
extensive service engagement.
PMID- 28423859
TI - Evidence for Busines Intelligence in Health Care: A Literature Review.
AB - This paper outlines a systematic literature review undertaken to establish
current evidence regarding the impact of Business Intelligence (BI) on health
system decision making and organizational performance. The review also examined
BI implementation factors contributing to these constructs. Following the
systematic review, inductive content analysis was used to categorize themes
within the eight articles identified. This study demonstrated there is little
evidence based literature focused on BI impact on organizational decision making
and performance within health care. There was evidence found that BI does improve
decision making. Implementation success was found to be dependent on several
factors, many of which relate to broader organizational culture and readiness.
PMID- 28423860
TI - Development of a Web-Based Quality Dashboard Including a Toolbox to Improve Pain
Management in Dutch Intensive Care.
AB - Audit and feedback (A&F) is a common strategy to improve quality of care. Meta
analyses have indicated that A&F may be more effective in realizing desired
change when baseline performance is low, it is delivered by a supervisor or
colleague, it is provided frequently and in a timely manner, it is delivered in
both verbal and written formats, and it includes specific targets and an action
plan. However, there is little information to guide operationalization of these
factors. Researchers have consequently called for A&F interventions featuring
well-described and carefully justified components, with their theoretical
rationale made explicit. This paper describes the rationale and development of a
quality dashboard including an improvement toolbox for four previous developed
pain indicators, guided by Control Theory.
PMID- 28423861
TI - A Digital Framework to Support Providers and Patients in Diabetes Related
Behavior Modification.
AB - We present Diabetes Web-Centric Information and Support Environment (D-WISE) that
features: (a) Decision support tool to assist family physicians to administer
Behavior Modification (BM) strategies to patients; and (b) Patient BM application
that offers BM strategies and motivational interventions to engage patients. We
take a knowledge management approach, using semantic web technologies, to model
the social cognition theory constructs, Canadian diabetes guidelines and BM
protocols used locally, in terms of a BM ontology that drives the BM decision
support to physicians and BM strategy adherence monitoring and messaging to
patients. We present the qualitative analysis of D-WISE usability by both
physicians and patients.
PMID- 28423864
TI - Adsorption of Uranyl Ions at the Nano-hydroxyapatite and Its Modification.
AB - Nano-hydroxyapatite and its modification, hydroxyapatite with the excess of
phosphorus (P-HAP) and hydroxyapatite with the carbon ions built into the
structure (C-HAP), were prepared by the wet method. They were studied by means of
XRD, accelerated surface area and porosimetry (ASAP), and SEM. The size of
crystallites computed using the Scherrer method was nano-hydroxyapatite (HAP) =
20 nm; P-HAP-impossible to determine; C-HAP = 22 nm; nano-HAP/U(VI) = 13.7 nm; P
HAP/U(VI)-impossible to determine, C-HAP/U(VI) = 11 nm. There were determined
basic parameters characterizing the double electrical layer at the nano
HAP/electrolyte and P-HAP/electrolyte, C-HAP/electrolyte inter faces: density of
the surface charge and zeta potential. The adsorption properties of nano-HAP
sorbent in relation to U(VI) ions were studied by the batch technique. The
adsorption processes were rapid in the first 60 min and reached the equilibrium
within approximately 120 min (for P-HAP) and 300 min (for C-HAP and nano-HAP).
The adsorption process fitted well with the pseudo-second-order kinetics. The
Freundlich, Langmuir-Freundlich, and Dubinin-Radushkevich models of isotherms
were examined for their ability to the equilibrium sorption data. The maximum
adsorption capabilities (q m ) were 7.75 g/g for P-HAP, 1.77 g/g for C-HAP, and
0.8 g/g for HAP at 293 K.
PMID- 28423865
TI - PEALD-Grown Crystalline AlN Films on Si (100) with Sharp Interface and Good
Uniformity.
AB - Aluminum nitride (AlN) thin films were deposited on Si (100) substrates by using
plasma-enhanced atomic layer deposition method (PEALD). Optimal PEALD parameters
for AlN deposition were investigated. Under saturated deposition conditions, the
clearly resolved fringes are observed from X-ray reflectivity (XRR) measurements,
showing the perfectly smooth interface between the AlN film and Si (100). It is
consistent with high-resolution image of the sharp interface analyzed by
transmission electron microscope (TEM). The highly uniform thickness throughout
the 2-inch size AlN film with blue covered surface was determined by
spectroscopic ellipsometry (SE). Grazing incident X-ray diffraction (GIXRD)
patterns indicate that the AlN films are polycrystalline with wurtzite structure
and have a tendency to form (002) preferential orientation with increasing of the
thickness. The obtained AlN films could open up a new approach of research in the
use of AlN as the template to support gallium nitride (GaN) growth on silicon
substrates.
PMID- 28423866
TI - Relaxation behavior of polyethylene welded joints.
AB - The paper presents results of the investigation of structure relaxation and
thermal properties of PE-80 and PE-100 polyethylene hot-tool butt welds. It was
found that a weld with the re-crystallized crystalline structure is formed during
the welding of dissimilar types of polyethylene. It is shown that within a long
period (1 year) the relaxation occurs not only in amorphous but also in the
crystalline phase (crystalline alpha-form transforms into mixed alphabeta-form),
with respective changes in polyethylene properties.
PMID- 28423867
TI - High Efficiency, Low Power-Consumption DFB Quantum Cascade Lasers Without Lateral
Regrowth.
AB - Very low power-consumption distributed feedback (DFB) quantum cascade lasers
(QCLs) at the wavelength around 4.9 MUm were fabricated by conventional process
without lateral regrowth of InP:Fe or using sidewall grating. Benefitted from the
optimized materials and low waveguide loss, very low threshold current density of
0.5 kA/cm2 was obtained for a device with cavity length of 2 mm. Combined with
the partial-high-reflection coating, the 1-mm-long DFB QCL achieved low power
consumption continuous wave (CW) operation up to 105 degrees C. The CW threshold
power-consumptions were 0.72 and 0.78 W at 15 and 25 degrees C, respectively.
The maximum CW output power was over 110 mW at 15 degrees C and still more than
35 mW at 105 degrees C. At 15 degrees C, wall-plug efficiency of 5.5% and slope
efficiency of 1.8 W/A were deduced, which were very high for low power
consumption DFB QCLs.
PMID- 28423868
TI - Genetic parameters of calving ease using sire-maternal grandsire model in Korean
Holsteins.
AB - OBJECTIVE: Calving ease (CE) is a complex reproductive trait of economic
importance in dairy cattle. This study was aimed to investigate the genetic
merits of CE for Holsteins in Korea. METHODS: A total of 297,614 field records of
CE, from 2000 to 2015, from first parity Holstein heifers were recorded
initially. After necessary data pruning such as age at first calving (18 to 42
mo), gestation length, and presence of sire information, final datasets for CE
consisted of 147,526 and 132,080 records for service sire calving ease (SCE) and
daughter calving ease (DCE) evaluations, respectively. The CE categories were
ordered and scores ranged from CE1 to CE5 (CE1, easy; CE2, slight assistance;
CE3, moderate assistance; CE4, difficult calving; CE5, extreme difficulty
calving). A linear transformation of CE score was obtained on each category using
Snell procedure, and a scaling factor was applied to attain the spread between 0
(CE5) and 100% (CE1). A sire-maternal grandsire model analysis was performed
using ASREML 3.0 software package. RESULTS: The estimated direct heritability
(h2) from SCE and DCE evaluations were 0.11+/-0.01 and 0.08+/-0.01, respectively.
Maternal h2 estimates were 0.05+/-0.02 and 0.04+/-0.01 from SCE and DCE
approaches, respectively. Estimates of genetic correlations between direct and
maternal genetic components were -0.68+/-0.09 (SCE) and -0.71+/-0.09 (DCE). The
average direct genetic effect increased over time, whereas average maternal
effect was low and consistent. The estimated direct predicted transmitting
ability (PTA) was desirable and increasing over time, but the maternal PTA was
undesirable and decreasing. CONCLUSION: The evidence on sufficient genetic
variances in this study could reflect a possible selection improvement over time
regarding ease of calving. It is expected that the estimated genetic parameters
could be a valuable resource to formulate sire selection and breeding plans which
would be directed towards the reduction of calving difficulty in Korean
Holsteins.
PMID- 28423869
TI - Protective effects of Bacillus subtilis against Salmonella infection in the
microbiome of Hy-Line Brown layers.
AB - OBJECTIVE: This study investigated the effects of Bacillus subtilis CSL2 (B.
subtilis CSL2) administration before Salmonella challenge on the fecal microbiota
and microbial functionality of Hy-line Brown (HLB) laying hens. METHODS: Fecal
samples were collected from control (CON), Salmonella-infected (SAL) and
Salmonella-infected, probiotic-treated (PRO) groups before and after Salmonella
challenge for microbiome analysis using 16S rRNA gene pyrosequencing. RESULTS:
Infection with Salmonella led to decreased microbial diversity in hen feces;
diversity was recovered with Bacillus administration. In addition, Salmonella
infection triggered significant alterations in the composition of the fecal
microbiota. The abundance of the phylum Firmicutes decreased while that of
Proteobacteria, which includes a wide variety of pathogens, increased
significantly. Bacillus administration resulted in normal levels of abundance of
Firmicutes and Proteobacteria. Analysis of bacterial genera showed that
Salmonella challenge decreased the population of Lactobacillus, the most abundant
genus, and increased populations of Pseudomonas and Flavobacterium genera by a
factor of 3 to 5. On the other hand, Bacillus administration caused the abundance
of the Lactobacillus genus to recover to control levels and decreased the
population of Pseudomonas significantly. Further analysis of operational
taxonomic units revealed a high abundance of genes associated with two-component
systems and secretion systems in the SAL group, whereas the PRO group had more
genes associated with ribosomes. CONCLUSION: The results of this study indicate
that B. subtilis CSL2 administration can modulate the microbiota in HLB laying
hens, potentially acting as a probiotic to protect against Salmonella Gallinarum
infection.
PMID- 28423870
TI - Effects of physically effective neutral detergent fiber content on dry matter
intake, digestibility, and chewing activity in Korean native goats (Capra hircus
coreanae) fed with total mixed ration.
AB - OBJECTIVE: This experiment was to determine proper physical traits in the diet
for goats by investigating the effects of physically effective neutral detergent
fiber (peNDF) content on dry matter intake (DMI), digestibility, and chewing
activity in black goats fed with total mixed ration (TMR). METHODS: Six growing
wethers of Korean native black goats (Capra hircus coreanae) aged 8 months and
weighing between 26.9 kg and 27.1 kg (27.03+/-5.05 kg) were used in this
experiment. Three diets of varying peNDF content were obtained by original TMR
(T1), 12,000 rpm grinding (T2), and 15,500 rpm grinding (T3) of the same TMR
diet. The peNDF1.18 content of the experimental diets was 23.85%, 21.71%, and
16.22% for T1, T2, and T3, respectively. RESULTS: Average daily gain (ADG) was
higher in T2 group compared to those of the control and T3 groups, but ADG and
DMI were not affected by the dietary particle size and peNDF content. Also, there
was no difference between apparent nutrient digestibility of dry matter, crude
fiber, ether extract, neutral detergent fiber, and acid detergent fiber. Although
there was no significant difference, rumination and total chewing time were
associated with decreased peNDF content. CONCLUSION: The feeding of peNDF-based
TMR showed no impact on apparent nutrient digestibility and nitrogen balance.
Further studies are required with a wider range of dietary peNDF level and
particle size to better identify the effect of dietary peNDF and particle size on
chewing activity and performance in goats.
PMID- 28423871
TI - Behavioral characteristics of Hanwoo (Bos taurus coreanae) steers at different
growth stages and seasons.
AB - OBJECTIVE: This research analyzed behavioral characteristics of Hanwoo (Bos
taurus coreanae) steers during each season and growth stage to enable measurement
of the animals' welfare level for precision livestock farming. METHODS: A hundred
eight beef steers were divided into three equal groups at a Hanwoo farm according
to their growth stage: growing stage (GS), 8 months; early-fattening stage (EFS),
19 months; and late-fattening stage (LFS), 30 months. Twelve behavioral
categories were continuously recorded for 13 day-time hours in each four seasons
with three replications. RESULTS: Time spent standing was found to be
significantly longer in summer at all growth stages (p<0.05). Hanwoos at the GS
spent significantly longer standing time in spring and summer than those at the
EFS and LFS (p<0.05). Lying time in summer was the shortest for all growth stages
(p<0.05). Steers at the LFS spent significantly longer lying time than that at
the GS (p<0.05) in summer. For GS and EFS, time spent eating in spring and autumn
were longer than in summer and winter (p<0.05). Eating time was the longest for
the GS in spring, autumn, and winter, excluding for the LFS in winter (p<0.05).
Regarding ruminating, steers at the LFS spent significantly shorter time than
those at other stages in all seasons (p<0.05). GS and EFS steers showed the
longest walking time in summer compared with other seasons (p<0.05). At GS and
LFS, drinking time in summer was the longest of all seasons (p<0.05). Sleeping
time was significantly shorter in summer compared with the other seasons
(p<0.05). Self-grooming time was the longest in winter for all growth stages
(p<0.05). CONCLUSION: Steers were found to have more variable behavioral patterns
during summer and the GS and less active behaviors during the LFS, thus extra
care seems necessary during the GS, LFS, and summer period.
PMID- 28423872
TI - Potential antioxidant and lipid peroxidation inhibition of Phyllanthus acidus
leaf extract in minced pork.
AB - OBJECTIVE: This study investigated the effect of extraction solvents on
antioxidant bio-active compounds as well as potential antioxidant and lipid
peroxidation inhibition of Phyllanthus acidus (P. acidus) leaf extract in minced
pork. METHODS: The effect of various solvent systems of water, 25%, 50%, 75%
(v/v) ethanol in water and absolute ethanol on the extraction crude yield, total
phenolic content, total flavonoid content and in vitro antioxidant activities of
P. acidus leaves was determined. In addition, antioxidant activities of the
addition of crude extract from P. aciuds leaves at 2.5 and 5 g/kg in minced pork
on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2'-Azino-bis(3
ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation
decolorization, reducing power and inhibition of lipid peroxidation
(thiobarbituric acid reactive substances; TBARS) were determined. Moreover,
sensory evaluation of the samples was undertaken by using a 7-point hedonic
scale. RESULTS: The results showed that the highest crude yield (2.8 g/100 g dry
weight) was obtained from water which also had the highest recovery yield for
total phenolic content, total flavonoid content and the strongest antioxidant
activity. The addition of crude water extract from P. acidus leaves was more
effective in retarding lipid peroxidation and higher antioxidant activity than
control and butylated hydroxytoluene in minced pork. In particular, the samples
containing P. acidus extract had no significant effect on the sensory scores of
overall appearance, color, odor, texture, flavor, and overall acceptability
compared to the control. CONCLUSION: Water solvent was an optimally appropriate
solvent for P. acidus leaf extraction because of its ability to yield the highest
amount of bio-active compounds and in vitro antioxidant property. Particularly,
P. acidus crude water extract also strongly expressed the capacity to retard
lipid oxidation, radical scavenging, radical cation decolorization and reducing
power in minced pork. The results of this study indicated that P. acidus leaf
extract could be used as natural antioxidant in the pork industry.
PMID- 28423873
TI - Replacing groundnut cake with gluten meals of rice and maize in diets for growing
Sahiwal cattle.
AB - OBJECTIVE: This experiment investigated the effect of isonitrogenous replacement
of groundnut cake (GNC) by rice gluten meal (RGM) and maize gluten meal (MGM) at
75% level on nutrient intake, apparent digestibility, growth performance and
related blood constituents in growing Sahiwal cattle. METHODS: Eighteen Sahiwal
calves were divided into three groups, based on average body weight (87.24 kg)
and age (6 to 12 mo), and treatments were assigned to the different groups
randomly. The first group (GP-I) was kept as control and received GNC-based
concentrate mixture. In second (GP-II) and third (GP-III) groups, 750 g/kg
nitrogen (N) of GNC was substituted by RGM and MGM respectively, with similar
forage:concentrate ratio (56:44). RESULTS: The 90 days of experimental feeding
revealed that intake of dry matter, crude protein and digestibility coefficients
for all nutrients did not differ among groups. Furthermore, although N balance
was greater (p<=0.05) for GP-III than GP-I and GP-II, average daily gain was
similar between GP-I and GP-II but greater (p<=0.05) for GP-III. In addition,
feed efficiency and related haematological variables did not differ due to
treatments. CONCLUSION: Nutritional worth of GNC and RGM was highly comparable in
terms of intake, digestibility and growth in growing calves. However, MGM was
found to be more efficacious in improving growth rate than RGM at 75% replacement
level of GNC protein.
PMID- 28423874
TI - The relationship between the variants in the 5'-untranslated regions of equine
chorionic gonadotropin genes and serum equine chorionic gonadotropin levels.
AB - OBJECTIVE: An experiment was conducted to study the association between the
single nucleotide polymorphisms (SNPs) in 5'-untranslated regions (5'-UTR) of
equine chorionic gonadotropin (eCG) genes and the serum eCG levels. METHODS: SNPs
in 5'-UTR of eCG genes were screened across 10 horse breeds, including 7 Chinese
indigenous breeds and 3 imported breeds using iPLEX chemistry, and the
association between the serum eCG levels of 174 pregnant Da'an mares and their
serum eCG levels (determined with ELISA) was analyzed. RESULTS: Four SNPs were
identified in the 5'-UTR of the eCGalpha gene, and one of them was unique in the
indigenous breeds. There were 2 SNPs detected at the 5' end of the eCGbeta
subunit gene, and one of them was only found in the Chinese breeds. The SNP
g.39948246T>C at the 5'-UTR of eCGalpha was associated significantly with eCG
levels of 75-day pregnant mare serum (p<0.05) in Da'an mares. Prediction analysis
on binding sites of transcription factors showed that the g.39948246T>C mutation
causes appearance of the specific binding site of hepatocyte nuclear factor 3
forkhead homolog 2 (HFH-2), which is a transcriptional repressor belonging to the
forkhead protein family of transcription factors. CONCLUSION: The SNP
g.39948246T>C at the 5'-UTR of eCGalpha is associated with eCG levels of 75-day
pregnant mare serum (p<0.05).
PMID- 28423875
TI - Adaptive selection at agouti gene inferred breed specific selection signature
within the indigenous goat populations.
AB - Objective: The aim of this study was to calculate selection signatures at
possible loci leading to population differentiation, as well as pattern of
selection of agouti gene within the local goat breeds and its correlation among
other animal species to reveal molecular evolution. Methods: The high Fst outlier
method corresponding to Fst distribution was used to identify the loci subject to
positive selection. According to the empirical distribution of Fst estimates, we
selected the SNPs having high Fst outlier corresponded to the upper 1% of the
distribution as the loci under selection. In five goat populations 14 SNPs were
determined from 14 genes to be subjected to natural or artificial selection. The
selective pressures were measured with the non-synonymous to synonymous
substitution rate ratio omega (dN/dS), where omega=1, omega<1 and omega>1
correspond to neutral, purifying and positive selection, respectively. Results:
The loci were analyzed for positive selection and the most locus undergone
positive selection was Agouti-2. Positive selection of agouti gene was analyzed
with FDIST analysis using outlier approach, agouti gene showed a significant
positive selection in the outlier area as there was a strong evidence of positive
selection for this locus because of its low heterozygosity. Analysis showed that
previously agouti gene was initially under purified selection, but now is under
adaptive positive selection. The data was explored by two sets of nested models
(M1-M2; M7-M8) and LRT was concluded by using likelihood estimates. The
nucleotide sequence of goat agouti gene showed closer coding sequence similarity
to agouti gene of sheep (99.3%), buffalo (98.3%) cattle (98%), and wild yak
(95.3%) and human (85.5%). Conclusion: This study provides strong evidence of
breed specific selection of the agouti gene within the indigenous goat breeds. We
also demonstrate comprehensive approaches formulating systemic searches for
genes; that have undergone positive selection in lineages.
PMID- 28423876
TI - Effects of confinement on physiological and psychological responses and
expression of interleukin 6 and brain derived neurotrophic factor mRNA in
primiparous and multiparous weaning sows.
AB - OBJECTIVE: The present study aimed to investigate whether the long-lasting,
recurrent restricting of sows leads to the physiological and psychological
reaction of discomfort. METHODS: Sows (Large White) that had experienced
restricting for about 0.5 or 3 years and age-matched sows kept in a group housing
system (loose sows) were compared. Pupillary light reflex parameters were
measured at the weaning stage. Immediately after slaughter, blood samples were
taken to measure serum cortisol levels, and the brain was dissected, gene
expression in the hippocampus, frontal cortex and hypothalamus was analyzed.
RESULTS: The serum cortisol levels were higher in the confined sows than in the
loose sows. The full maturity, but not the young adolescent, confined sows had
longer latency time in the onset of pupil constriction than their loose
counterparts. Real-time polymerase chain reaction analyses revealed an increased
expression of interleukin 6 mRNA in the hippocampus and decreased expression of
brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a
lesser extent in the frontal cortex of the full maturity confined sows, compared
with the full maturity loose sows. CONCLUSION: Taken together, these data
indicated that recurrent restricting stress in full maturity sows leads to the
physiological and psychological reaction of discomfort.
PMID- 28423877
TI - Identification of Polymorphisms and Association of Five KAP Genes with Sheep Wool
Traits.
AB - Objective: The objective of this study was to detect and evaluate the
associations of possible polymorphisms of six exon regions within five KAP genes
(KAP6.1, KAP8.1, KAP8.2, KRTAP9-2 and KAP16.4 [KAP16.4-1 and KAP16.4-2]) with
wool traits in 418 Chinese Merino (Xinjiang type) (CMXT) sheep. Methods: The PCR
SSCP (polymerase chain reaction-based single-strand conformation polymorphism),
DNA sequencing, and the gene pyramiding effect methods were used to detect the
polymorthisms and the association analysis. Results: We detected 21 mutation loci
(single-nucleotide polymorphisms) within the five KAP genes. Of these loci, three
(EX_33-35insA, EX_45-47insA, and EX_61-63insT) were indel mutations, four
mutation loci (EX_54-56delA, EX_52-54delC, EX_45-47delA, and EX_34-36delA) were
deletion mutations, and 14 (EX_C35A, EX_G132C, EX_C54T, EX_G162A, EX_C166A,
EX_A167T, EX_C85A, EX_A133C, EX_G89A, EX_G137A, EX_G188A, EX_A190C, EX_A196T, and
EX_G78C) were silent mutations. Association analysis indicated that different
genotypes of six primer (P1-P6) fragments were significantly associated with
traits, (P < 0.05) in CMXT sheep. Analysis of the gene pyramiding effect between
the different genotypes of the gene sites KAP6.1 and KRTAP9-2, KAP8.1 and KAP8.2,
and KAP16.4-1 and KAP16.4-2, each genotype in a gene site was combined with all
the genotypes of another gene site and formed the different combined genotypes in
each pair of combined site, indicated a total of 36 types of possible combined
genotypes in the analyzed population. Compared with the other combined genotypes,
the combinations AAEE, GGII, and KKNN at gene sites KAP6.1-KRTAP9-2, KAP8.1
KAP8.2, and KAP16.4-1-KAP16.4-2, respectively, had a greater effect on wool
traits (P < 0.05). Conclusion: Our results indicate that the single-nucleotide
polymorphisms and combined genotypes have a significant effect on the wool traits
of CMXT individuals, and could be used as candidate markers for sheep wool traits
in sheep breeding programs.
PMID- 28423878
TI - Effects of alfalfa flavonoids on the production performance, immune system, and
ruminal fermentation of dairy cows.
AB - OBJECTIVE: The objective of this study was to examine the effects of alfalfa
flavonoids on the production performance, immunity, and ruminal fermentation of
dairy cows. METHODS: The experiments employed four primiparous Holstein cows
fitted with ruminal cannulas, and used a 4*4 Latin square design. Cattle were fed
total mixed ration supplemented with 0 (control group, Con), 20, 60, or 100 mg of
alfalfa flavonoids extract (AFE) per kg of dairy cow body weight (BW). RESULTS:
The feed intake of the group receiving 60 mg/kg BW of AFE were significantly
higher (p<0.05) than that of the group receiving 100 mg/kg BW. Milk yields and
the fat, protein and lactose of milk were unaffected by AFE, while the total
solids content of milk reduced (p = 0.05) linearly as AFE supplementation was
increased. The somatic cell count of milk in group receiving 60 mg/kg BW of AFE
was significantly lower (p<0.05) than that of the control group. Apparent total
tract digestibility of neutral detergent fiber and crude protein showed a
tendency to increase (0.050.05), but changes in bacterial composition were
found. CONCLUSION: From the present study, it is inferred that EW is beneficial
for rumen fermentation, and weaning when the feed intake of the starter reached
750 g showed much better results.
PMID- 28423880
TI - Effects of vertebral number variations on carcass traits and genotyping of
Vertnin candidate gene in Kazakh sheep.
AB - OBJECTIVE: The vertebral number is associated with body length and carcass
traits, which represents an economically important trait in farm animals. The
variation of vertebral number has been observed in a few mammalian species.
However, the variation of vertebral number and quantitative trait loci in sheep
breeds have not been well addressed. METHODS: In our investigation, the
information including gender, age, carcass weight, carcass length and the number
of thoracic and lumbar vertebrae from 624 China Kazakh sheep was collected. The
effect of vertebral number variation on carcass weight and carcass length was
estimated by general linear model. Further, the polymorphic sites of Vertnin
(VRTN) gene were identified by sequencing, and the association of the genotype
and vertebral number variation was analyzed by the one-way analysis of variance
model. RESULTS: The variation of thoracolumbar vertebrae number in Kazakh sheep
(18 to 20) was smaller than that in Texel sheep (17 to 21). The individuals with
19 thoracolumbar vertebrae (T13L6) were dominant in Kazakh sheep (79.2%). The
association study showed that the numbers of thoracolumbar vertebrae were
positively correlated with the carcass length and carcass weight, statistically
significant with carcass length. To investigate the association of thoracolumbar
vertebrae number with VRTN gene, we genotyped the VRTN gene. A total of 9
polymorphic sites were detected and only a single nucleotide polymorphism (SNP)
(rs426367238) was suggested to associate with thoracic vertebral number
statistically. CONCLUSION: The variation of thoracolumbar vertebrae number
positively associated with the carcass length and carcass weight, especially with
the carcass length. VRTN gene polymorphism of the SNP (rs426367238) with
significant effect on thoracic vertebral number could be as a candidate marker to
further evaluate its role in influence of thoracolumbar vertebral number.
PMID- 28423881
TI - Effects of calcium propionate on the fermentation quality and aerobic stability
of alfalfa silage.
AB - OBJECTIVE: To assess the potency of calcium propionate (CAP) used as silage
additive, an experiment was carried out to evaluate the effect of CAP on the
nitrogen transformation, fermentation quality and aerobic stability of alfalfa
silages. METHODS: Alfalfa was ensiled with four levels of CAP (5, 10, 15, and 20
g/kg of fresh weight [FW]) in laboratory silos for 30 days. After opening, the
silages were analyzed for the chemical and microbiological characteristics, and
subjected to an aerobic stability test. RESULTS: The increasing proportion of CAP
did not affect pH, lactic acid (LA) concentrations and yeast counts, while
linearly decreased counts of enterobacteria (p = 0.029), molds (p<0.001) and
clostridia (p<0.001), and concentrations of acetic acid (p<0.001), propionic acid
(p<0.001), butyric acid (p<0.001), and ethanol (p = 0.007), and quadratically (p
= 0.001) increased lactic acid bacteria counts. With increasing the proportion of
CAP, the dry matter (DM) loss (p<0.001), free amino acid N (p<0.001), ammonia N
(p = 0.004), and non-protein N (p<0.001) contents were linearly reduced, whereas
DM (p = 0.048), water soluble carbohydrate (p<0.001) and peptide N (p<0.001)
contents were linearly increased. The highest Flieg's point was found in CAP10
(75.9), represented the best fermentation quality. All silages treated with CAP
improved aerobic stability as indicated by increased stable hours compared with
control. CONCLUSION: The addition of CAP can suppress the undesirable
microorganisms during ensiling and exposure to air, thereby improving the
fermentation quality and aerobic stability as well as retarding the proteolysis
of alfalfa silage. It is suggested that CAP used as an additive is recommended at
a level of 10 g/kg FW.
PMID- 28423882
TI - Various levels of rapeseed meal in weaning pig diets from weaning to finishing
periods.
AB - OBJECTIVE: This experiment was conducted to investigate the influence of rapeseed
meal (RSM) supplementation in weaning pig diet on growth performance, blood
profile, carcass characteristics and economic analysis on weaning to finishing
pigs. METHODS: A total of 120 cross bred ([Yorkshire*Landrace]*Duroc) weaning
pigs were allotted to 5 treatments in a randomized complete block design. Each
treatment had 4 replications with 6 pigs per pen. Five different levels of RSM
(0%, 2%, 4%, 6%, and 8%) were used as dietary treatments. RESULTS: Overall, no
treatment showed significant differences in growth performance with increased
dietary RSM levels. The concentration of blood urea nitrogen (BUN) decreased as
dietary RSM levels increased in 6 weeks (linear response, p<0.01). Total
cholesterol, high density lipoprotein cholesterol, low density lipoprotein
cholesterol, triiodothyronine, and thyroxine showed no significant differences,
neither were there any significant differences in the immune response (IgG and
IgA). As the dietary RSM levels of weaning pig diet were increased, no
differences were found among dietary treatments upon performing proximate
analyses of the pork after finishing. The influence of RSM supplementation on
nutrient digestibility and nitrogen retention were not affected by dietary RSM
levels either. With increased dietary RSM levels in the weaning pig diet, no
differences among dietary treatments were found after performing proximate
analyses of the pork's physiochemical properties. In addition, there were no
significant differences observed in pork colors, pH levels, and economic
benefits. CONCLUSION: Consequently, this experiment demonstrated that weaning
pig's diet containing RSM influenced BUN concentration, but there were no
detrimental effects on the growth performance of weaning pigs with up to 8% RSM
in the diet.
PMID- 28423883
TI - Comparison of growth performance of Berkshire purebreds and crossbreds sired by
Hereford and Tamworth breeds raised in alternative production system.
AB - OBJECTIVE: The objective of the present study was to compare growth performance
of Berkshire purebred pigs (BB), Hereford (HB) and/or Tamworth (TB) sired
Berkshire crossbred pigs reared in a hoop structure in two experiments. METHODS:
In the first experiment, BB was compared to TB while HB and TB were compared in
the second. Body weights (BW) were recorded at 3 days of age and every 28 days
from birth until 140 days of age. There was no significant difference between the
BW of BB and TB, but HB was heavier than TB by 84 days of age. Least square means
of average daily gain (ADG) were evaluated using one-way analysis of variance.
RESULTS: The mean parity (+/-standard deviation) of the sows was 3.42+/-2.14 and
a total of 45 farrowing occurred from year 2012 to 2014. The mean number of total
born, number born alive, number of mummies, and number weaned were 9.23+/-2.52,
7.87+/-2.53, 0.04+/-0.21, and 5.94+/-2.74, respectively. Parity did not have a
significant effect on the growth performance of the pigs. For BB and TB, there
was only one time frame in which there was a significant difference in the ADG:
between 28 and 56 days of age. For HB and TB, the overall ADG of HB was
significantly greater than the total ADG of TB. CONCLUSION: The breed of the sire
did not affect the growth performance of the progeny between Berkshire purebreds
and Tamworth*Berkshire crossbreds. The breed of the sire did have an effect
between Hereford and Tamworth sired Berkshire crossbreds (p<0.05). The Hereford
sired pigs were found to have increased growth performance compared to Tamworth
sired.
PMID- 28423884
TI - Integrating market chain assessments with zoonoses risk analysis in two cross
border pig value chains in Lao PDR.
AB - OBJECTIVE: Lao PDR's recent accession to the World Trade Organization
necessitates a greater understanding of the patterns and risk of livestock
production in order to better align national policy with the Agreement on the
Application of Sanitary and Phytosanitary Measures. This eco-health study was
conducted to improve understanding of the interrelations between market chains
and zoonotic infection risks at two strategic cross border points between Lao
PDR, Thailand and Viet Nam. METHODS: Information gained from smallholder
farmer/trader interviews was integrated with serological surveys for pig
associated zoonoses-including hepatitis E virus (HEV), Taenia solium (T. solium)
and trichinella-to identify potential linkages between disease risk and pig
production and slaughter in low input systems common across the country. RESULTS:
Trichinella and HEV exposure was high in both humans and pigs in both study
areas, significantly associated with pig slaughter and the subsequent consumption
and handling of raw pork products. T. solium demonstrated a strong geographical
and ethnic association with the northern study area bordering Vietnam. With the
right knowledge and accessible, affordable inputs, the majority of smallholder
farmers indicated a willingness to invest more in pig production, which could
simultaneously improve livelihoods and decrease exposure to HEV, Trichinella, and
T. solium through increased access to formal markets and an improved slaughter
processes. CONCLUSION: The linkages identified when assessing disease risk in the
context of potential economic and cultural drivers of transmission highlight the
importance of a systems-based approach for the detection and control of zoonotic
disease, and contributes to an improved understanding of the Lao PDR livestock
sector.
PMID- 28423885
TI - Effect of fermented biogas residue on growth performance, serum biochemical
parameters, and meat quality in pigs.
AB - OBJECTIVE: This study investigated the effect of fermented biogas residue (FBR)
of wheat on the performance, serum biochemical parameters, and meat quality in
pigs. METHODS: We selected 128 pigs (the mean initial body weight was 40.24+/
3.08 kg) and randomly allocated them to 4 groups (1 control group and 3 treatment
groups) with 4 replicates per group and 8 pigs per pen in a randomized complete
block design based on initial body weight and sex. The control group received a
corn-soybean meal-based diet, the treatment group fed diets containing 5%, 10%,
and 15% FBR, respectively (abbreviated as FBR5, FBR10, and FBR15, respectively).
Every group received equivalent-energy and nitrogen diets. The test lasted 60
days and was divided into early and late stages. Blood and carcass samples were
obtained on 60 d. Meat quality was collected from two pigs per pen. RESULTS:
During the late stage, the average daily feed intake and average daily gain of
the treatment groups was greater than that of the control group (p<0.05). During
the entire experiment, the average daily gain of the treatment groups was higher
than that of the control group (p<0.05). Fermented biomass residue did not
significantly affect serum biochemical parameters or meat quality, but did affect
amino acid profiles in pork. The contents of Asp, Arg, Tyr, Phe, Leu, Thr, Ser,
Lys, Pro, Ala, essential amino acids, non-essential amino acids, and total amino
acids in pork of FBR5 and FBR10 were greater than those of the control group
(p<0.05). CONCLUSION: These combined results suggest that feeding FBR could
increase the average daily gain and average daily feed intake in pigs and the
content of several flavor-promoting amino acids.
PMID- 28423886
TI - Adiponectin induced AMP-activated protein kinase impairment mediates insulin
resistance in Bama mini-pig fed high-fat and high-sucrose diet.
AB - OBJECTIVE: Adipose tissue is no longer considered as an inert storage organ for
lipid, but instead is thought to play an active role in regulating insulin
effects via secretion adipokines. However, conflicting reports have emerged
regarding the effects of adipokines. In this study, we investigated the role of
adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs.
METHODS: An obesity model was established in Bama mini-pigs, by feeding with high
fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry
levels were measured, and intravenous glucose tolerance test was performed.
Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor
necrosis factor alpha (TNF-alpha), and glucose-induced insulin secretion were
also examined by radioimmunoassay. AMP-activated protein kinase (AMPK)
phosphorylation in skeletal muscle, which is a useful insulin resistance marker,
was examined by immunoblotting. Additionally, associations of AMPK
phosphorylation with plasma adipokines and homeostasis model assessment of
insulin resistance (HOMA-IR) index were assessed by Pearce's correlation
analysis. RESULTS: Obese pigs showed hyperglycemia, high triglycerides, and
insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and
IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and
adipose tissue, corroborating data from obese mice and humans. However,
circulating resistin and TNF-alpha showed no difference, while the values of TNF
alpha in adipose tissue were significantly higher in obese pigs, also in
agreement with data from obese humans but not rodent models. Moreover, strong
associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and
HOMA-IR index were obtained. CONCLUSION: AMPK impairment induced by adiponectin
decrease mediates insulin resistance in high-fat and high-sucrose diet induction.
In addition, Bama mini-pig has the possibility of a conformable model for human
metabolic diseases.
PMID- 28423887
TI - The effect of lactation number, stage, length, and milking frequency on milk
yield in Korean Holstein dairy cows using automatic milking system.
AB - OBJECTIVE: The aim of the current study was to describe the relationship between
milk yield and lactation number, stage, length and milking frequency in Korean
Holstein dairy cows using an automatic milking system (AMS). METHODS: The
original data set consisted of observations from April to October 2016 of 780
Holstein cows, with a total of 10,751 milkings. Each time a cow was milked by an
AMS during the 24 h, the AMS management system recorded identification numbers of
the AMS unit, the cow being milking, date and time of the milking, and milk yield
(kg) as measured by the milk meters installed on each AMS unit, date and time of
the lactation, lactation stage, milking frequency (NoM). Lactation stage is
defined as the number of days milking per cows per lactation. Milk yield was
calculated per udder quarter in the AMS and was added to 1 record per cow and
trait for each milking. Milking frequency was measured the number of milkings per
cow per 24 hour. RESULTS: From the study results, a significant relationship was
found between the milk yield and lactation number (p<0.001), with the maximum
milk yield occurring in the third lactation cows. We recorded the highest milk
yield, in a greater lactation length period of early stage (55 to 90 days) at a
4* milking frequency/d, and the lowest milk yield was observed in the later stage
(>201 days) of cows. Also, milking frequency had a significant influence on milk
yield (p<0.001) in Korean Holstein cows using AMS. CONCLUSION: Detailed knowledge
of these factors such as lactation number, stage, length, and milking frequency
associated with increasing milk yield using AMS will help guide future
recommendations to producers for maximizing milk yield in Korean Dairy
industries.
PMID- 28423888
TI - Effects of two litter amendments on air NH3 levels in broiler closed-houses.
AB - OBJECTIVE: High NH3 emissions from poultry houses are reported to have negative
impacts on health, welfare and safety of birds and humans, and on the
environment. Objective of the present study was to determine the effects of two
litter amendments on the NH3 levels in broiler closed houses under hot-humid
conditions. METHODS: Giving a completely randomize design, nine closed houses,
each housed 32,500 birds on paddy husk litter, were randomly allocated into two
treatment (Mizuho; a bacterial culture mix and Rydall OE; an enzymatic
biocatalyst) and control groups. NH3 levels were determined thrice a day (0600,
1200, and 1800 h), at three heights from the litter surface (30, 90, and 150 cm),
at 20 predetermined locations of a house, from day 1 to 41. RESULTS: Rydall
significantly reduced the NH3 level compared to control and Mizuho. NH3 levels at
30 cm were significantly higher than that of 90 and 150 cm. The NH3 levels at 30
cm height were higher than 25 ppm level from day 9, 11, and 13 in Mizuho,
control, and Rydall groups, respectively to day 41. NH3 levels at 150 cm height
were higher than maximum threshold limit of 50 ppm for human exposure from day
12, 14, and 15 in Mizuho, control, and Rydall groups, respectively to day 33.
Being significantly different among each other, the NH3 level was highest and
lowest at 0600 and 1800 h. Litter amendments had no significant effects on growth
performance. Rydall significantly increased the litter N content on day 24.
CONCLUSION: It was concluded that the NH3 levels of closed house broiler
production facilities under tropical condition are so high that both birds and
workers are exposed to above recommended levels during many days of the growing
period. Compared to microbial culture, the enzymatic biocatalyst was found to be
more effective in reducing NH3 level.
PMID- 28423889
TI - WITHDRAWN:Polymorphism Of Bola-DRB3 gene and its association with embryo
development after in vitro fertilization in Slovak spotted x Holstein-Fresian
crossbred cattle.
AB - Ahead of Print article withdrawn by publisher.
PMID- 28423890
TI - Physicochemical characteristics and fatty acid profiles of muscle tissues from
Hanwoo steers fed a total mixed ration supplied with medicinal plant by-products.
AB - OBJECTIVE: Using medicinal plant by-products (MPBP) as feed additives may be an
eco-friendly option as substitutes for feedstuffs and may assist in reducing the
improper disposal of MPBP. Therefore, this study was conducted to evaluate the
influences of MPBP on the meat quality of Hanwoo steers fed a total mixed ration
(TMR). METHODS: Twenty seven steers (body weight = 573+/-57 kg) were randomly
divided into three treatments with a control group and two tested groups as
follows: control, 1,000 g/kg TMR; treatment 1 (MPBP30), 970 g/kg TMR and 30 g/kg
MPBP; treatment 2 (MPBP50), 950 g/kg TMR and 50 g/kg MPBP. RESULTS: Average daily
gain, feed conversion ratio and the Commission Internationale de l'Eclairage L*
of muscle were improved (p<0.05, respectively) by MPBP30. Stearic acid (C18:0)
was decreased (linear effect, p = 0.012), while oleic acid (C18:1) was increased
(linear effect, p = 0.055) by MPBP level. Saturated fatty acid (SFA) and
polyunsaturated fatty acid (PUFA) were decreased for MPBP50 while unsaturated
fatty acid (USFA) and monounsaturated fatty acid (MUFA) were increased for MPBP
50. USFA and SFA ratio was increased for MPBP50 as well. CONCLUSION: These
results indicated that MPBP supplementation in Hanwoo steers fed a TMR increased
feed efficiency and meat color (lightness) with altering fatty acid proportions.
Therefore, MPBP may be successfully used in ruminant feeding.
PMID- 28423891
TI - Effective Thermal Inactivation of the Spores of Bacillus cereus Biofilms Using
Microwave.
AB - Microwave sterilization was performed to inactivate the spores of biofilms of
Bacillus cereus involved in foodborne illness. The sterilization conditions, such
as the amount of water and the operating temperature and treatment time, were
optimized using statistical analysis based on 15 runs of experimental results
designed by the Box-Behnken method. Statistical analysis showed that the optimal
conditions for the inactivation of B. cereus biofilms were 14 ml of water, 108
degrees C of temperature, and 15 min of treatment time. Interestingly, response
surface plots showed that the amount of water is the most important factor for
microwave sterilization under the present conditions. Complete inactivation by
microwaves was achieved in 5 min, and the inactivation efficiency by microwave
was obviously higher than that by conventional steam autoclave. Finally, confocal
laser scanning microscopy images showed that the principal effect of microwave
treatment was cell membrane disruption. Thus, this study can contribute to the
development of a process to control food-associated pathogens.
PMID- 28423892
TI - O2 Plasma Etching and Antistatic Gun Surface Modifications for CNT Yarn
Microelectrode Improve Sensitivity and Antifouling Properties.
AB - Carbon nanotube (CNT) based microelectrodes exhibit rapid and selective detection
of neurotransmitters. While different fabrication strategies and geometries of
CNT microelectrodes have been characterized, relatively little research has
investigated ways to selectively enhance their electrochemical properties. In
this work, we introduce two simple, reproducible, low-cost, and efficient surface
modification methods for carbon nanotube yarn microelectrodes (CNTYMEs): O2
plasma etching and antistatic gun treatment. O2 plasma etching was performed by a
microwave plasma system with oxygen gas flow and the optimized time for treatment
was 1 min. The antistatic gun treatment flows ions by the electrode surface; two
triggers of the antistatic gun was the optimized number on the CNTYME surface.
Current for dopamine at CNTYMEs increased 3-fold after O2 plasma etching and 4
fold after antistatic gun treatment. When the two treatments were combined, the
current increased 12-fold, showing the two effects are due to independent
mechanisms that tune the surface properties. O2 plasma etching increased the
sensitivity due to increased surface oxygen content but did not affect surface
roughness while the antistatic gun treatment increased surface roughness but not
oxygen content. The effect of tissue fouling on CNT yarns was studied for the
first time, and the relatively hydrophilic surface after O2 plasma etching
provided better resistance to fouling than unmodified or antistatic gun treated
CNTYMEs. Overall, O2 plasma etching and antistatic gun treatment improve the
sensitivity of CNTYMEs by different mechanisms, providing the possibility to tune
the CNTYME surface and enhance sensitivity.
PMID- 28423893
TI - The Least Stable Isomer of BN Naphthalene: Toward Predictive Trends for the
Optoelectronic Properties of BN Acenes.
AB - The least stable isomer of the parental BN naphthalene series has been
synthesized in a simple four-step sequence. Its experimental electronic structure
characterization via UV-PES, cyclic voltammetry, and UV-vis spectroscopy in
direct comparison with three other known BN naphthalene isomers has established
two guiding principles for predicting the electronic structures of BN acene
compounds: (1) Orientational BN isomers have similar HOMO-LUMO gaps. (2) For each
pair of orientational BN isomers, the more thermodynamically stable compound has
the lower HOMO energy. Furthermore, we demonstrate that BN/CC isosterism in the
context of BN-9,1-Naph can impact crystal packing to favor a cofacial pi-stack
motif.
PMID- 28423894
TI - Stratification and Size Segregation of Ternary and Polydisperse Colloidal
Suspensions during Drying.
AB - We investigate the drying process of three-component and polydisperse colloidal
suspensions using Brownian dynamics simulations. We have previously reported
(Phys. Rev. Lett. 2016, 116, 118301) on the drying of binary mixtures. For binary
mixtures, we found that a gradient of colloidal osmotic pressure develops during
drying and that this leads to the final film being stratified with a layer of
smaller particles on top of a layer of larger particles. Here, we find that
stratification by size is very general and also occurs in ternary and
polydisperse mixtures. We name the segregation effect colloidal diffusiophoresis.
In particular, we show that by changing the composition of a ternary mixture,
different stratification morphologies can be achieved and hence the film
properties can be tuned. In polydisperse spheres, colloidal diffusiophoresis
leads to enrichment in the large particles at the bottom part of the film,
whereas the top part is enriched with smaller particles. This segregation means
that in the final film, the particle size distribution depends on height. Thus,
the properties of the film will then depend on height. We propose a model that
predicts a power-law dependence of the phoretic velocity on particle size.
Results from the model and simulation show a good agreement.
PMID- 28423895
TI - Supramolecularly Engineered pi-Amphiphile.
AB - This article describes self-assembly of supramolecularly engineered naphthalene
diimide (NDI)-derived amphiphiles NDI-1 and NDI-2. They have the same
hydrophobic/hydrophilic balance but merely differ by a single functional group,
amide or ester. They exhibit distinct self-assembly in water; NDI-1 forms
hydrogel, which upon aging forms crystals, whereas NDI-2 forms micelles as
revealed by in-depth structural analysis using cryo-TEM, dynamic light
scattering, and small-angle X-ray scattering studies. These results suggest that
the H-bonding among the amide groups fully regulates the self-assembly by
overruling the packing parameters. Further, the present study elucidates sharp
lower critical solution temperature exhibited by these pi-amphiphiles, which has
been extensively studied for many important applications of water-soluble
polymers but hardly known in the literature of small-molecule surfactants.
Control experiments with the same water-soluble hydrophilic wedge did not show
such a property, confirming this to be a consequence of the supramolecular
polymerization by extended amide-amide H-bonding and not inherent to the
structure of the hydrophilic wedge containing oligo-oxyethylene chains.
PMID- 28423896
TI - Synthesis, Structure, and Catalysis of Palladium Complexes Bearing a Group 13
Metalloligand: Remarkable Effect of an Aluminum-Metalloligand in Hydrosilylation
of CO2.
AB - Efficient synthesis and catalysis of a series of palladium complexes having a
group 13 metalloligand (Al, Ga, In) are reported utilizing 6,6"
bis(phosphino)terpyridine as a new scaffold for Pd-E bonds (E = Al, Ga, In).
Systematic investigation revealed unique characteristics of the Al-metalloligand
in both structure and reactivity, which exhibited the highest catalytic activity
for hydrosilylation of CO2 ever reported (TOF = 19 300 h-1). This study
demonstrated fine-tuning of catalyst activity by the precisely designed
metalloligand is a promising approach for new catalyst development in synthetic
organometallic chemistry.
PMID- 28423897
TI - Orders of Magnitude Reduction of Rapid Coagulation Rate with Decreasing Size of
Silica Nanoparticles.
AB - The modification of the classical Smoluchowski theory for the rapid coagulation
rate of colloidal particles, which takes account of the effect of the squeezing
flow between colliding particles, has been widely accepted because it predicts
experimental results adequately. However, it is not clear whether the modified
theory, in which the coagulation rate is independent of the particle size, is
applicable even to nanoparticles in solutions. In the present study, the rapid
coagulation rates of silica particles in various 2 M chloride and 1 M potassium
solutions were measured by using a low-angle light-scattering apparatus, and the
dependence of rapid coagulation rate on the particle diameter, Dp, was
investigated extensively. It was clearly shown that the rapid coagulation rate of
spherical silica particles reduces by the orders of magnitude with decreasing
particle size at Dp <= 300 nm, whereas it coincides with the value predicted by
the modified theory at Dp >= 300 nm. A possible mechanism is proposed, and an
analytical equation, which predicts the dramatic reduction in the rapid
coagulation rate with decreasing particle size, is derived.
PMID- 28423898
TI - Spotlights: Volume 8, Issue 8.
PMID- 28423899
TI - Viewpoints on the 2017 Pacific Conference on Spectroscopy and Dynamics.
PMID- 28423901
TI - Estimation of Nanodiamond Surface Charge Density from Zeta Potential and
Molecular Dynamics Simulations.
AB - Molecular dynamics simulations of nanoparticles (NPs) are increasingly used to
study their interactions with various biological macromolecules. Such simulations
generally require detailed knowledge of the surface composition of the NP under
investigation. Even for some well-characterized nanoparticles, however, this
knowledge is not always available. An example is nanodiamond, a nanoscale diamond
particle with surface dominated by oxygen-containing functional groups. In this
work, we explore using the harmonic restraint method developed by Venable et al.,
to estimate the surface charge density (sigma) of nanodiamonds. Based on the Gouy
Chapman theory, we convert the experimentally determined zeta potential of a
nanodiamond to an effective charge density (sigmaeff), and then use the latter to
estimate sigma via molecular dynamics simulations. Through scanning a series of
nanodiamond models, we show that the above method provides a straightforward
protocol to determine the surface charge density of relatively large (> ~100 nm)
NPs. Overall, our results suggest that despite certain limitation, the above
protocol can be readily employed to guide the model construction for MD
simulations, which is particularly useful when only limited experimental
information on the NP surface composition is available to a modeler.
PMID- 28423902
TI - Tribute to Klaus Schulten.
PMID- 28423900
TI - Methodology for the Simulation of Molecular Motors at Different Scales.
AB - Millisecond-scale conformational transitions represent a seminal challenge for
traditional molecular dynamics simulations, even with the help of high-end
supercomputer architectures. Such events are particularly relevant to the study
of molecular motors-proteins or abiological constructs that convert chemical
energy into mechanical work. Here, we present a hybrid-simulation scheme
combining an array of methods including elastic network models, transition path
sampling, and advanced free-energy methods, possibly in conjunction with
generalized-ensemble schemes to deliver a viable option for capturing the
millisecond-scale motor steps of biological motors. The methodology is already
implemented in large measure in popular molecular dynamics programs, and it can
leverage the massively parallel capabilities of petascale computers. The
applicability of the hybrid method is demonstrated with two examples, namely
cyclodextrin-based motors and V-type ATPases.
PMID- 28423903
TI - Biography of Klaus Schulten.
PMID- 28423904
TI - Colleagues of Klaus Schulten.
PMID- 28423905
TI - Abbreviated Curriculum Vitae of Klaus Schulten.
PMID- 28423906
TI - Selected Publications of Klaus Schulten.
PMID- 28423907
TI - Effects of Active Site Mutations on Specificity of Nucleobase Binding in Human
DNA Polymerase eta.
AB - Human DNA polymerase eta (Pol eta) plays a vital role in protection against skin
cancer caused by damage from ultraviolet light. This enzyme rescues stalled
replication forks at cyclobutane thymine-thymine dimers (TTDs) by inserting
nucleotides opposite these DNA lesions. Residue R61 is conserved in the Pol eta
enzymes across species, but the corresponding residue, as well as its neighbor
S62, is different in other Y-family polymerases, Pol iota and Pol kappa. Herein,
R61 and S62 are mutated to their Pol iota and Pol kappa counterparts. Relative
binding free energies of dATP to mutant Pol eta*DNA complexes with and without a
TTD were calculated using thermodynamic integration. The binding free energies of
dATP to the Pol eta*DNA complex with and without a TTD are more similar for all
of these mutants than for wild-type Pol eta, suggesting that these mutations
decrease the ability of this enzyme to distinguish between a TTD lesion and
undamaged DNA. Molecular dynamics simulations of the mutant systems provide
insights into the molecular level basis for the changes in relative binding free
energies. The simulations identified differences in hydrogen-bonding, cation-pi,
and pi-pi interactions of the side chains with the dATP and the TTD or thymine
thymine (TT) motif. The simulations also revealed that R61 and Q38 act as a clamp
to position the dATP and the TTD or TT and that the mutations impact the balance
among the interactions related to this clamp. Overall, these calculations suggest
that R61 and S62 play key roles in the specificity and effectiveness of Pol eta
for bypassing TTD lesions during DNA replication. Understanding the basis for
this specificity is important for designing drugs aimed at cancer treatment.
PMID- 28423909
TI - Ripping RNA by Force Using Gaussian Network Models.
AB - Using force as a probe to map the folding landscapes of RNA molecules has become
a reality thanks to major advances in single molecule pulling experiments.
Although the unfolding pathways under tension are complicated to predict, studies
in the context of proteins have shown that topology is the major determinant of
the unfolding landscapes. By building on this finding we study the responses of
RNA molecules to force by adapting Gaussian network model (GNM) that represents
RNAs using a bead-spring network with isotropic interactions. Cross-correlation
matrices of residue fluctuations, which are analytically calculated using GNM
even upon application of mechanical force, show distinct allosteric communication
as RNAs rupture. The model is used to calculate the force-extension curves at
full thermodynamic equilibrium, and the corresponding unfolding pathways of four
RNA molecules subject to a quasi-statically increased force. Our study finds that
the analysis using GNM captures qualitatively the unfolding pathway of T.
ribozyme elucidated by the optical tweezers measurement. However, the simple
model cannot capture features, such as bifurcation in the unfolding pathways or
the ion effects, in the forced-unfolding of RNAs.
PMID- 28423908
TI - Dependence of the Enzymatic Velocity on the Substrate Dissociation Rate.
AB - Enzymes are biological catalysts that play a fundamental role in all living
systems by supporting the selectivity and the speed for almost all cellular
processes. While the general principles of enzyme functioning are known, the
specific details of how they work at the microscopic level are not always
available. Simple Michaelis-Menten kinetics assumes that the enzyme-substrate
complex has only one conformation that decays as a single exponential. As a
consequence, the enzymatic velocity decreases as the dissociation (off) rate
constant of the complex increases. Recently, Reuveni et al. [ Proc. Natl. Acad.
Sci. USA 2014 , 111 , 4391 - 4396 ] showed that it is possible for the enzymatic
velocity to increase when the off rate becomes higher, if the enzyme-substrate
complex has many conformations which dissociate with the same off rate constant.
This was done using formal mathematical arguments, without specifying the nature
of the dynamics of the enzyme-substrate complex. In order to provide a physical
basis for this unexpected result, we derive an analytical expression for the
enzymatic velocity assuming that the enzyme-substrate complex has multiple states
and its conformational dynamics is described by rate equations with arbitrary
rate constants. By applying our formalism to a complex with two conformations, we
show that the unexpected off rate dependence of the velocity can be readily
understood: If one of the conformations is unproductive, the system can escape
from this "trap" by dissociating, thereby giving the enzyme another chance to
form the productive enzyme-substrate complex. We also demonstrate that the
nonmonotonic off rate dependence of the enzymatic velocity is possible not only
when all off rate constants are identical, but even when they are different. We
show that for typical experimentally determined rate constants, the nonmonotonic
off rate dependence can occur for micromolar substrate concentrations. Finally,
we discuss the relation of this work to the problem of optimizing the flux
through singly occupied membrane channels and transporters.
PMID- 28423910
TI - Conformational Preference of Serogroup B Salmonella O Polysaccharide in Presence
and Absence of the Monoclonal Antibody Se155-4.
AB - Salmonella infection is a major public health problem worldwide. Antibodies
directed toward the O polysaccharide (OPS) of S. Typhimurium, a serogroup B
nontyphoidal Salmonella serovar, have protected against fatal infection in animal
models. The OPS is known to undergo O-acetylation, though the impact of these
modifications on antibody binding is poorly understood. Using molecular
simulations, we assessed the conformational properties and antigen-antibody
interactions of deacetylated and O-acetylated S. Typhimurium OPS when bound by
monoclonal anti-OPS IgG Se155-4. Our findings indicate that (i) the alpha-d
abequose (8) monosaccharide makes important interactions with Se155-4, (ii) the
deacetylated form binds to the antibody in two conformations, (iii) the acetyl
group at alpha-l-rhamnose (5) traps the acetylated O-antigenic saccharide in one
of those two conformations when bound to the antibody; (iv) the dominant
conformation sampled by both unbound saccharides only occurs in the deacetylated
antibody complex; and (v) both unbound saccharides sample the second bound
conformation to a small extent (2-4%). These observations provide insights into
the conformational preference of an antigenic saccharide when bound to a well
characterized specific monoclonal antibody, and suggest possible important
properties of vaccine induced antibodies following immunization with live
attenuated and OPS-based subunit vaccines.
PMID- 28423911
TI - Token Economy: A Systematic Review of Procedural Descriptions.
AB - The token economy is a well-established and widely used behavioral intervention.
A token economy is comprised of six procedural components: the target
response(s), a token that functions as a conditioned reinforcer, backup
reinforcers, and three interconnected schedules of reinforcement. Despite decades
of applied research, the extent to which the procedures of a token economy are
described in complete and replicable detail has not been evaluated. Given the
inherent complexity of a token economy, an analysis of the procedural
descriptions may benefit future token economy research and practice. Articles
published between 2000 and 2015 that included implementation of a token economy
within an applied setting were identified and reviewed with a focus on evaluating
the thoroughness of procedural descriptions. The results show that token economy
components are regularly omitted or described in vague terms. Of the articles
included in this analysis, only 19% (18 of 96 articles reviewed) included
replicable and complete descriptions of all primary components. Missing or vague
component descriptions could negatively affect future research or applied
practice. Recommendations are provided to improve component descriptions.
PMID- 28423912
TI - Antifungal activity of cinnamic acid and benzoic acid esters against Candida
albicans strains.
AB - Candida albicans is an important opportunistic fungal pathogen capable of
provoking infection in humans. In the present study, we evaluated the antifungal
effect of 23 ester derivatives of the cinnamic and benzoic acids against 3 C.
albicans strains (ATCC-76645, LM-106 and LM-23), as well as discuss their
Structure-Activity Relationship (SAR). The antifungal assay results revealed that
the screened compounds exhibited different levels of activity depending on
structural variation. Among the ester analogues, methyl caffeate (5) and methyl 2
nitrocinnamate (10) were the analogues that presented the best antifungal effect
against all C. albicans strains, presenting the same MIC values (MIC = 128
MUg/mL), followed by methyl biphenyl-2-carboxylate (21) (MIC = 128, 128 and 256
MUg/mL for C. albicans LM-106, LM-23, and ATCC-76645, respectively). Our results
suggest that certain molecular characteristics are important for the antifungal
action.
PMID- 28423913
TI - Application of IATA - A case study in evaluating the global and local performance
of a Bayesian network model for skin sensitization.
AB - The information characterizing key events in an Adverse Outcome Pathway (AOP) can
be generated from in silico, in chemico, in vitro and in vivo approaches.
Integration of this information and interpretation for decision making are known
as integrated approaches to testing and assessment (IATA). One such IATA was
published by Jaworska et al., which describes a Bayesian network model known as
ITS-2. The current work evaluated the performance of ITS-2 using a stratified
cross-validation approach. We also characterized the impact of replacing the most
significant component of the network, output from the expert system TIMES-SS,
with structural alert information from the OECD Toolbox and Toxtree. Lack of
structural alerts or TIMES-SS predictions yielded a sensitization potential
prediction of 79%. If the TIMES-SS prediction was replaced by a structural alert
indicator, the network predictivity increased up to 87%. The original network's
predictivity was 89%. The local applicability domain of the original ITS-2
network was also evaluated using reaction mechanistic domains to understand what
types of chemicals ITS-2 was able to make the best predictions for. We found that
the original network was successful at predicting which chemicals would be
sensitizers, but not at predicting their potency.
PMID- 28423914
TI - Current views on neuropeptide Y and diabetes-related atherosclerosis.
AB - Diabetes-induced atherosclerotic cardiovascular disease is the leading cause of
death of diabetic patients. Neuronal regulation plays a critical role in glucose
metabolism and cardiovascular function under physiological and pathological
conditions, among which, neurotransmitter neuropeptide Y has been shown to be
closely involved in these two processes. Elevated central neuropeptide Y level
promotes food intake and reduces energy expenditure, thereby increasing
adiposity. Neuropeptide Y is co-localized with noradrenaline in central and
sympathetic nervous systems. As a major peripheral vascular contractive
neurotransmitter, through interactions with its receptors, neuropeptide Y has
been implicated in the pathology and progression of diabetes, by promoting the
proliferation of endothelial cells and vascular fibrosis, which may contribute to
diabetes-induced cardiovascular disease. Neuropeptide Y also participates in the
pathogenesis of atherosclerosis, the major form of cardiovascular disease, via
aggravating endothelial dysfunction, growth of vascular smooth muscle cells,
formation of foam cells and platelets aggregation. This review highlights the
causal role of neuropeptide Y and its receptor system in the development of
diabetes mellitus and one of its complications: atherosclerotic cardiovascular
disease. The information from this review provides both critical insights onto
the mechanisms underlying the pathogenesis of atherosclerosis and evidence for
the development of therapeutic strategies.
PMID- 28423915
TI - Isolation of flavonoids from apple peel using novel graphene oxide cotton fiber.
AB - A novel graphene oxide cotton fibre (GOF) was used to adsorb flavonoids from
crude ethanol extracts derived from apple peels. Ultra-high pressure liquid
chromatography-mass spectrometry was used to analyse polyphenol content, and the
resulting data demonstrated that GOF-based flash chromatography can be used to
efficiently separate polyphenols from sugars and can facilitate the removal of
95% of the sugar content. Flavonoids can be easily separated from phenolic acids.
Chalcones and flavonols were eluted with 100% methanol and subsequently flavan-3
ols can be eluted with 0.04 M sodium hydroxide. The novel GOF has the potential
to be used in the isolation of flavonoids.
PMID- 28423916
TI - Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and
Evidence-Based Management.
AB - OBJECTIVE: To review the incidence, risk factors, and management of pegfilgrastim
induced bone pain (PIBP). DATA SOURCES: PubMed was searched from 1980 to March
31, 2017, using the terms pegfilgrastim and bone pain. STUDY SELECTION AND DATA
EXTRACTION: English-language, human studies and reviews assessing the incidence,
risk factors, and management of PIBP were incorporated. DATA SYNTHESIS: A total
of 3 randomized, prospective studies and 2 retrospective studies evaluated
pharmacological management of PIBP. Naproxen compared with placebo demonstrated a
reduction in the degree, incidence, and duration of bone pain secondary to
pegfilgrastim. Loratadine was not effective in reducing the incidence of bone
pain prophylactically, but a retrospective study evaluating dual antihistamine
blockade with loratadine and famotidine demonstrated a decreased incidence in
bone pain when administered before pegfilgrastim. CONCLUSION: Naproxen is
effective at managing PIBP. Although commonly used, antihistamines have a paucity
of data supporting their use. Dose reductions of pegfilgrastim and opioids may
also be potential management options; however, data supporting these treatment
modalities are scarce.
PMID- 28423917
TI - Management of Opioid-Induced Constipation in Hospice Patients.
AB - BACKGROUND: Constipation is a common symptom in patients with advanced disease
taking opioids. Opioid-induced constipation (OIC) is commonly treated with
laxatives and stool softeners. Recently, newer agents have come to market which
broaden options for patients in whom first-line therapies are not effective.
OBJECTIVE: To determine what pharmacologic regimens are currently used in hospice
programs to prevent and treat OIC, whether those regimens have changed with the
introduction of newer agents and evidence discouraging the use of docusate, and
whether hospice programs are standardizing the management of OIC. METHODS: An
online 10-item questionnaire was disseminated by the National Hospice and
Palliative Care Organization. Questions addressed demographics; first-, second-
and third-line pharmacologic treatments included in bowel protocols; whether
prescribing practices have changed in the last 5 years; and percentage of
patients receiving specific constipation therapies. RESULTS: The majority of
organizations (68.8%) responded that at least 90% of patients were prescribed a
bowel regimen on admission to hospice and 84.4% stated that they have a guideline
or protocol for managing OIC. The most commonly used preparations for the
treatment of OIC for patients during their length of stay in hospice were senna
plus docusate, senna alone, docusate alone, bisacodyl, polyethylene glycol 3350,
and lactulose. Over 75% of hospice organizations claimed they never used
methylnaltrexone, linaclotide, lubiprostone, or naloxegol. CONCLUSION: This
survey provides insight into recent practices of hospice organizations in the
treatment of OIC. As more agents come to market, it is likely that management of
OIC will continue to evolve.
PMID- 28423919
TI - Joint attention difficulties in autistic adults: An interactive eye-tracking
study.
AB - Joint attention - the ability to coordinate attention with a social partner - is
critical for social communication, learning and the regulation of interpersonal
relationships. Infants and young children with autism demonstrate impairments in
both initiating and responding to joint attention bids in naturalistic settings.
However, little is known about joint attention abilities in adults with autism.
Here, we tested 17 autistic adults and 17 age- and nonverbal intelligence
quotient-matched controls using an interactive eye-tracking paradigm in which
participants initiated and responded to joint attention bids with an on-screen
avatar. Compared to control participants, autistic adults completed fewer trials
successfully. They were also slower to respond to joint attention bids in the
first block of testing but performed as well as controls in the second block.
There were no group differences in responding to spatial cues on a non-social
task with similar attention and oculomotor demands. These experimental results
were mirrored in the subjective reports given by participants, with some
commenting that they initially found it challenging to communicate using eye
gaze, but were able to develop strategies that allowed them to achieve joint
attention. Our study indicates that for many autistic individuals, subtle
difficulties using eye-gaze information persist well into adulthood.
PMID- 28423918
TI - Expanding the Palliative Care Domains to Meet the Needs of a Community-Based
Supportive Care Model.
AB - BACKGROUND: Whole person care is appropriate for seriously ill persons. The
current framework of palliative care domains in the National Consensus Project
(NCP) Guidelines for Quality Palliative Care offers an opportunity to reassess
the domains of care delivered at home, earlier in the course of illness.
OBJECTIVE: This qualitative study was used to test the applicability of a
proposed, expanded set of domains. The results were used to inform a home-based,
upstream model of supportive care for serious illness. METHODS: Quotes relating
to the experience of late-life serious illness were derived from transcripts of
12 semi-structured group interviews conducted with patients, family, and
professionals. Quotes originally coded to the NCP domains of palliative care were
then coded to the proposed domain set, which included new categories of
family/caregiver, legal/financial, and legacy/bereavement domains. RESULTS: A
total of 489 quotes were assigned to the proposed expanded set of domains. One
hundred one (19%) coded to the family/caregiver domain, 28 (5%) to the
legacy/bereavement domain, and 27 (5%) to the legal/financial domain. Ninety
seven (87%) of the 111 quotes coded to family/caregiver had been initially coded
to the NCP social aspects of care. Family/caregiver themes included challenges,
rewards, insights, and family growth. CONCLUSION: The preponderance of family
related issues suggests that including the family domain may promote recognition
and support of family caregivers and the services they provide. Although this
study provides some support for including the legacy/bereavement and
legal/financial domains, additional research is needed to determine whether there
is a basis for including them in the domain structure.
PMID- 28423920
TI - 'Medical' marijuana is incompatible with mental health promotion.
PMID- 28423921
TI - Phytochemical investigations and evaluation of antimutagenic activity of the
alcoholic extract of Glycosmis pentaphylla and Tabernaemontana coronaria by Ames
test.
AB - Chemical investigation of root bark of Glycosmis pentaphylla and stem bark of
Tabernaemontana coronaria led to the isolation of three carbazole alkaloids
glycozoline, glycozolidine and methyl carbazole 3-carboxylate, two furoquinoline
alkaloids skimmianine and dictamine, an acridone alkaloid arborinine, three
monomeric indole alkaloids coronaridine, 10-methoxy coronaridine and
tabernaemontanine, and two dimeric indole alkaloids voacamine and
tabernaelegantine B. Their structures were established by detailed spectral
analysis. Mutagenic and antimutagenic potential of methanol extract of both plant
materials were evaluated by Ames test against known positive mutagens 2
aminofluorine, 4-nitro-O-phenylenediamine and sodium azide using Salmonella
typhimurium TA 98 and TA 100 bacterial strains both in the presence and absence
of S9. Both the extracts were non-mutagenic in nature. Both the extracts of G.
pentaphylla and T. coronaria exhibited significant antimutagenic activity against
NPD and sodium azide for S. typhimurium TA98 and TA100 strains. The results
indicated that the extracts could counteract the mutagenicity induced by
different genotoxic compounds.
PMID- 28423922
TI - Activation of GPR15 and its involvement in the biological effects of smoking.
AB - Smoking is one of the most significant modifiable environmental risk factors for
many diseases. Smoking causes excessive mortality worldwide. Despite decades of
long research, there has not been a clear understanding regarding the molecular
mechanism that makes smoking harmful to health. Some recent studies have found
that smoking influences most significantly the expression and methylation of
GPR15. GPR15 is an orphan receptor that is involved in the regulation of the
innate immunity and the T-cell trafficking in the intestinal epithelium. Further
studies have confirmed that GPR15 is very strongly involved in smoking and
smoking-induced molecular changes. Therefore, the altered expression and
epigenetic regulation of GPR15 could have a significant role in the health impact
of smoking. Impact statement The review describes an orphan receptor GPR15 that
has recently been found to be influenced by smoking. This makes GPR15 very
sensitive and adequate biomarker for smoking and smoking studies. Also,
activation of GPR15 by smoking could help to explain its effects on health.
PMID- 28423923
TI - A new wortmannine derivative from a Tripterygium wilfordii endophytic fungus
Talaromyces wortmannii LGT-4.
AB - A new wortmannine derivative named wortmannine E (1) was isolated from
Talaromyces wortmannii LGT-4, an endophytic fungus of Tripterygium wilfordii. Its
structure was established by 1D and 2D NMR spectra.
PMID- 28423924
TI - Advances in siRNA delivery in cancer therapy.
AB - RNA interference (RNAi)-based therapeutic approaches are under vibrant
scrutinisation to seek cancer cure. siRNA suppress expression of the carcinogenic
genes by targeting the mRNA expression. However, in vivo systemic siRNA therapy
is hampered by the barriers such as poor cellular uptake, instability under
physiological conditions, off-target effects and possible immunogenicity. To
overcome these challenges, systemic siRNA therapy warrants the development of
clinically suitable, safe, and effective drug delivery systems. Herein, we review
the barriers, potential siRNA drug delivery systems, and application of siRNA in
clinical trials for cancer therapy. Further research is required to harness the
full potential of siRNA as a cancer therapeutic.
PMID- 28423925
TI - Antioxidant and alpha-glucosidase inhibitory activities of isoflavonoids from the
rhizomes of Ficus tikoua Bur.
AB - A new unique isoflavone derivatives with a cyclic-monoterpene-substituent,
ficusin C (1), together with five known compounds (2-6), were isolated from the
rhizomes of Ficus tikoua. Their structures were elucidated on the basis of
spectroscopic data interpretation, mass spectrometric analysis and comparison
with literature data of related compounds. Antioxidant and alpha-glucosidase
inhibitory activities of these compounds were evaluated by 1,1-diphenyl-2
picryhydrazyl (DPPH) radical-scavenging assay and alpha-glucosidase inhibitory
experiment, respectively.
PMID- 28423926
TI - Antibacterial activity of a triterpenoid saponin from the stems of Caesalpinia
pulcherrima Linn.
AB - A new compound 1 was isolated from the methanolic extract of the stems of the
Caesalpinia pulcherrima Linn. along with a reported compound (2) 3-O-beta-D
glucopyranosyl-(1->4)-beta-D-xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)
alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D
glucopyranosyl ester. The new compound 1 has m.p. 272-274 degrees C, m.f.
C46H74O17, [M]+ m/z 898. It was characterised as 3-O-beta-D-glucopyranosyl-(1->4)
alpha-L-arabinopyranosyl hederagenin 28-O-beta-D- xylopyranosyl ester by various
colour reactions, chemical degradations and spectral analyses. Antibacterial
activity of compound 1 was screened against various Gram-positive and Gram
negative bacteria and showed significant results.
PMID- 28423927
TI - The Nation's Disaffected and Workplace Health Promotion.
PMID- 28423928
TI - Engaging Parents to Promote Children's Nutrition and Health.
AB - PURPOSE: Using the Academy of Nutrition and Dietetics benchmarks as a framework,
this study examined childcare providers' (Head Start [HS], Child and Adult Care
Food Program [CACFP] funded, and non-CACFP) perspectives regarding communicating
with parents about nutrition to promote children's health. DESIGN: Qualitative.
SETTING: State-licensed center-based childcare programs. PARTICIPANTS: Full-time
childcare providers (n = 18) caring for children 2 to 5 years old from varying
childcare contexts (HS, CACFP funded, and non-CACFP), race, education, and years
of experience. METHODS: In-person interviews using semi-structured interview
protocol until saturation were achieved. Thematic analysis was conducted.
RESULTS: Two overarching themes were barriers and strategies to communicate with
parents about children's nutrition. Barriers to communication included-(a)
parents are too busy to talk with providers, (b) parents offer unhealthy foods,
(c) parents prioritize talking about child food issues over nutrition, (d)
providers are unsure of how to communicate about nutrition without offending
parents, and (e) providers are concerned if parents are receptive to nutrition
education materials. Strategies for communication included-(a) recognize the
benefits of communicating with parents about nutrition to support child health,
(b) build a partnership with parents through education, (c) leverage policy
(federal and state) to communicate positively and avoid conflict, (d) implement
center-level practices to reinforce policy, and (e) foster a respectful
relationship between providers and parents. CONCLUSION: Policy and environmental
changes were recommended for fostering a respectful relationship and building a
bridge between providers and parents to improve communication about children's
nutrition and health.
PMID- 28423930
TI - The Art of Health Promotion ideas for improving health outcomes.
PMID- 28423931
TI - Comparative Effectiveness of Two Walking Interventions on Participation, Step
Counts, and Health.
AB - PURPOSE: To (1) compare the effects of two worksite-based walking interventions
on employee participation rates; (2) compare average daily step counts between
conditions, and; (3) examine the effects of increases in average daily step
counts on biometric and psychologic outcomes. DESIGN: We conducted a cluster
randomized trial in which six employer groups were randomly selected and randomly
assigned to condition. SETTING: Four manufacturing worksites and two office-based
worksite served as the setting. SUBJECTS: A total of 474 employees from six
employer groups were included. INTERVENTION: A standard walking program was
compared to an enhanced program that included incentives, feedback, competitive
challenges, and monthly wellness workshops. MEASURES: Walking was measured by
self-reported daily step counts. Survey measures and biometric screenings were
administered at baseline and 3, 6, and 9 months after baseline. ANALYSIS:
Analysis used linear mixed models with repeated measures. RESULTS: During 9
months, participants in the enhanced condition averaged 726 more steps per day
compared with those in the standard condition (p < .001). A 1000-step increase in
average daily steps was associated with significant weight loss for both men (
3.8 lbs.) and women (-2.1 lbs.), and reductions in body mass index (-0.41 men,
0.31 women). Higher step counts were also associated with improvements in mood,
having more energy, and higher ratings of overall health. CONCLUSIONS: An
enhanced walking program significantly increases participation rates and daily
step counts, which were associated with weight loss and reductions in body mass
index.
PMID- 28423932
TI - Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor
Tendon Repairs.
AB - BACKGROUND: The aim of the study was to compare biomechanical strength, repair
times, and repair values for zone II core flexor tendon repairs. METHODS: A total
of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index
through small finger and randomized into one of 5 repair groups: 4-stranded cross
stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double
Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double
stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided
suture). Repairs were measured in situ and their repair times were measured.
Tendons were linearly loaded to failure and multiple biomechanical values were
measured. The repair value was calculated based on operating room costs, repair
times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc
statistical analysis were used to compare repair data. RESULTS: The braided
cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the
4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to
perform. The total repair value was the highest for braided cruciate ( P > .05)
compared with all other repairs. Barbed suture did not outperform any repairs in
any categories. CONCLUSIONS: The braided cruciate was the strongest of the tested
flexor tendon repairs. The 2-mm gapping and maximum load to failure for this
repair approached similar historical strength of other 6- and 8-stranded repairs.
In this study, suture cost was negligible in the overall repair cost and should
be not a determining factor in choosing a repair.
PMID- 28423933
TI - Phytochemical composition and biological activities of Artemisia quettensis
Podlech ethanolic extract.
AB - The present study aim to investigate the phytochemical composition,
antibacterial, antioxidant and anticancer activities of the ethanolic extract
from aerial parts of Artemisia quettensis Podlech. The aerial part of A.
quettensis Podlech extract was used for Gas chromatography-mass spectrometry (GC
MS) analysis, antioxidant, antibacterial and anticancer activities. GC/MS
analysis of extract from this plant showed 23 major components and the most
dominant components were acetic acid, [4-(1-hydroxy-1-methylethyl) cyclohex-1
enyl] methyl ester (13.88%), trans-Phytol (10.06%) and 2,6-Dimethyl-2,6-octadiene
1,8-diol diacetate (6.8%). The extract had significant antibacterial and
anticancer effects. The highest percentage of antioxidant activity was 78.46% at
2 mg/mL concentration of extract. Moreover, the highest antibacterial effects of
extract were against to gram-positive bacteria and the IC50 cell cytotoxicity
value on HT29 cell line in 24 h, 48 h and 72 h were 31.54, 6.08 and 2.96 mg/mL,
respectively. From this study, A. quettensis Podlech could be considered as a
promising source for novel drug compounds.
PMID- 28423934
TI - Estimating Dementia and Receipt of Informal Care Using Behavioral Risk Factor
Surveillance System Data.
AB - INTRODUCTION: Estimates of US adults with dementia differ widely and don't
distinguish adults living in the community. METHODS: Behavioral Risk Factor
Surveillance System data from 120 485 households in 21 states that used a
cognitive decline module in 2011 were used. Data for both respondents and other
adults with subjective cognitive decline (SCD) were included through proxy
responses. Using responses to questions about the receipt of informal care for
their SCD and diagnosed dementia, estimates were made for each state. RESULTS:
Overall, 2.9% (range: 1.5% in Tennessee to 5.3% in Arkansas) of all
noninstitutionalized adults in these states received informal care for their SCD
and 0.9% (range: 0.5% in Tennessee to 2.0% in Arkansas) were estimated to have
dementia. Limiting results to respondents reduced estimates significantly.
DISCUSSION: Combined results for respondents and nonrespondents from a
representative telephone survey provide varying estimates of SCD-related measures
across states, highlighting the need for state-specific estimates.
PMID- 28423935
TI - Supporting Simple Activity Engagement in Persons With Moderate to Severe
Alzheimer's Disease Through a Technology-Aided Program.
AB - OBJECTIVES: These 2 studies assessed a technology-aided program to support mild
physical exercise or simple occupational activity in participants with moderate
to severe Alzheimer's disease. METHODS: Study 1 included 11 participants who were
to perform a leg-raising response. Study 2 included 10 participants who were to
sort objects into different containers. The program ensured that they received
positive stimulation contingent on the responses and reminders/prompts after
periods of nonresponding. Each study was carried out according to a nonconcurrent
multiple baseline design across participants. RESULTS: The program was successful
in supporting mild physical exercise and activity with objects in the 2 groups of
participants, respectively. The participants also showed signs of positive
involvement (eg, smiles and verbalizations) during the sessions. Moreover, staff
personnel rated the program and its impact positively. CONCLUSION: The program
may be considered a practical resource for supporting positive engagement in
persons with moderate to severe Alzheimer's disease.
PMID- 28423936
TI - Relationship Quality and Distress in Caregivers of Persons With Dementia: A Cross
Sectional Study.
AB - This cross-sectional study aimed to investigate the relationship between
caregivers and care receivers, defined as home-dwelling family members with
dementia. We used a self-rating questionnaire, the Felt Expressed Emotion Rating
Scale (FEERS; 6 simple questions), to measure caregiver perceptions of the care
receiver's criticisms (CCs) and emotional overinvolvement (EOI) toward the
caregiver. We performed factor analyses to rank single items on the FEERS
pertaining to CC and EOI. We included 208 caregiver/care receiver pairs. Logistic
regression analyses tested associations between FEERS items and caregiver and
care receiver variables. The main contributors to caregiver perceptions of CC
were the caregiver's own distress and the amount of time spent with the care
receiver. Socially distressed caregivers perceived the care receiver as
emotionally overinvolved. When offering a psychosocial intervention, a tailored
program should target the caregiver's perceived relationship with the family
member and the caregiver's distress. The program should also endeavor to give the
caretaker more opportunities for leisure time.
PMID- 28423937
TI - Concordance of Several Subcellular Interactions Initiates Alzheimer's Dementia:
Their Reversal Requires Combination Treatment.
AB - The pathogenesis of Alzheimer's disease involves multiple pathways that, at the
macrolevel, include decreased proliferation plus increased loss affecting
neurons, astrocytes, and capillaries and, at the subcellular level, involve
several elements: amyloid/amyloid precursor protein, presenilins, the unfolded
protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the
Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented
show the intimate, anatomical interactions between neurons, astrocytes, and
capillaries; the interactions between the several subcellular factors affecting
those cells; and the treatments that are currently available and that might
correct dysfunctions in the subcellular factors. Available treatments include
lithium, valproate, pioglitazone, erythropoietin, and prazosin. Since the
subcellular pathogenesis involves multiple interacting elements, combination
treatment would be more effective than administration of a single drug directed
at only 1 element. The overall purpose of this presentation is to describe the
pathogenesis in detail and to explain the proposed treatments.
PMID- 28423938
TI - Validation of the Turkish Version of the Quick Mild Cognitive Impairment Screen.
AB - BACKGROUND: The objective of this study was to validate the Turkish version of
the Quick Mild Cognitive Impairment (Q mci-TR) screen. METHODS: In total, 100
patients aged >=65 years referred to a geriatric outpatient clinic with memory
loss were included. The Q mci was compared to the Turkish versions of the
standardized Mini-Mental State Examination and the Montreal Cognitive Assessment
(MoCA). RESULTS: The Q mci-TR had higher accuracy than the MoCA in discriminating
subjective memory complaints (SMCs) from cognitive impairment (mild cognitive
impairment [MCI] or dementia), of borderline significance after adjusting for age
and education ( P = .06). The Q mci-TR also had higher accuracy than the MoCA in
differentiating MCI from SMC, which became nonsignificant after adjustment ( P =
.15). A similar pattern was shown for distinguishing MCI from dementia. Test
reliability for the Q mci-TR was strong. CONCLUSION: The Q mci-TR is a reliable
and useful screening tool for discriminating MCI from SMC and dementia in a
Turkish population.
PMID- 28423939
TI - Erratum: "The Inhibitory Effect of Abietic Acid on Melanoma Cancer Metastasis and
Invasiveness In Vitro and In Vivo".
PMID- 28423940
TI - Preoperative Risk Factors for Complications in Elective Ankle and Hindfoot
Reconstruction.
AB - BACKGROUND: The purpose of this study was to examine medical, social, and
psychological factors associated with complications and reoperation after foot
and ankle reconstruction. METHODS: A retrospective chart review was conducted of
132 patients (135 feet; 139 operative cases) who had elective foot and ankle
reconstruction. Medical, social, and psychological variables were documented.
Primary outcomes included complications and reoperations. RESULTS: The overall
complication rate was 28% (39/139), and the reoperation rate was 17% (24/139).
Alcohol use (P = .03) and preoperative narcotic use (P = .02) were risk factors
for complications, with delayed wound healing more frequent in alcohol users (P =
.03) and deep infection (P = .045) and nonunion (P = .046) more frequent
preoperative narcotic use. Deep infection also was more frequent in tobacco users
(P < .01). Older patients were less likely to undergo reoperation (risk of
reoperation increased with age). Other variables were not associated with
increased complications. CONCLUSION: Patients who consumed alcohol or had been
prescribed any amount of narcotic within 3 months preoperatively were at
increased risk for complications. Patients who smoked were more likely to have a
wound infection. Surgeons should be aware of these factors and counsel patients
before surgery. LEVELS OF EVIDENCE: Level III: Retrospective comparative study.
PMID- 28423941
TI - Guide Pin Placement Technique for Total Ankle Replacement in Patients Who Had
Ipsilateral Total Knee Arthroplasty.
AB - : We describe a simple technique for guide pin placement for total ankle
replacement in patients who underwent previous ipsilateral total knee
arthroplasty. LEVELS OF EVIDENCE: Level V.
PMID- 28423942
TI - Natural gums of plant origin as edible coatings for food industry applications.
AB - Natural plant-based gums and their derivatives are widely utilized in food
industries, however, their applications as edible coatings to extend fresh fruits
and vegetable shelf-life has been explored recently. These natural polymeric
polysaccharides have many advantages as compared to synthetic polymers, because
they are biodegradable, nontoxic, economical and easily available in the
environment. Natural gums can also be semi synthetically modified to produce
derivatives, which can easily compete with the synthetic preservatives available
on the food market. In this review, the recent developments in the use of natural
gums and their derivatives as edible coatings have been explored and discussed.
PMID- 28423943
TI - High value added lipids produced by microorganisms: a potential use of sugarcane
vinasse.
AB - This review aims to present an innovative concept of high value added lipids
produced by heterotrophic microorganisms, bacteria and fungi, using carbon
sources, such as sugars, acids and alcohols that could come from sugarcane
vinasse, which is the main byproduct from ethanol production that is released in
the distillation step. Vinasse is a rich carbon source and low-cost feedstock
produced in large amounts from ethanol production. In 2019, the Brazilian
Ministry of Agriculture, Livestock and Food Supply estimates that growth of
ethanol domestic consumption will be 58.8 billion liters, more than double the
amount in 2008. This represents the annual production of more than 588 billion
liters of vinasse, which is currently used as a fertilizer in the sugarcane crop,
due to its high concentration of minerals, mainly potassium. However, studies
indicate some disadvantages such as the generation of Greenhouse Gas emission
during vinasse distribution in the crop, as well as the possibility of
contaminating the groundwater and soil. Therefore, the development of programs
for sustainable use of vinasse is a priority. One profitable alternative is the
fermentation of vinasse, followed by an anaerobic digester, in order to obtain
biomaterials such as lipids, other byproducts, and methane. Promising high value
added lipids, for instance carotenoids and polyunsaturated fatty acids (PUFAS),
with a predicted market of millions of US$, could be produced using vinasse as
carbon source, to guide an innovative concept for sustainable production. Example
of lipids obtained from the fermentation of compounds present in vinasse are
vitamin D, which comes from yeast sucrose fermentation and Omega 3, which can be
obtained by bacteria and fungi fermentation. Additionally, several other
compounds present in vinasse can be used for this purpose, including sucrose,
ethanol, lactate, pyruvate, acetate and other carbon sources. Finally, this paper
illustrates the potential market and microbial processes, using microorganisms,
for lipid production.
PMID- 28423944
TI - Emerging roles of long non-coding RNAs in plant response to biotic and abiotic
stresses.
AB - Spectacular progress in high-throughput transcriptome sequencing and expression
profiling using next-generation sequencing technologies have recently
revolutionized molecular biology and allowed massive advances in identifying the
genomic regions and molecular mechanisms underlying transcriptional regulation of
growth, development, and stress response. Through recent research, non-coding
RNAs, in particular long non-coding RNAs, have emerged as key regulators of
transcription in eukaryotes. Long non-coding RNAs are vastly heterogeneous groups
of RNAs that execute a broad range of essential roles in various biological
processes at the epigenetic, transcriptional, and post-transcriptional levels.
They modulate transcription through diverse mechanisms. Recently, numerous
lncRNAs have been identified to be associated with defense responses to biotic
and abiotic stresses. These have been suggested to perform indispensable roles in
plant immunity and adaptation to environmental conditions. However, only a few
lncRNAs have been functionally characterized in plants. In this paper, we
summarize the present knowledge of lncRNAs, review the recent advances in
understanding regulatory functions of lncRNAs, and highlight the emerging roles
of lncRNAs in regulating immune responses in plants.
PMID- 28423945
TI - On-line soft sensing in upstream bioprocessing.
AB - This review provides an overview and a critical discussion of novel possibilities
of applying soft sensors for on-line monitoring and control of industrial
bioprocesses. Focus is on bio-product formation in the upstream process but also
the integration with other parts of the process is addressed. The term soft
sensor is used for the combination of analytical hardware data (from sensors,
analytical devices, instruments and actuators) with mathematical models that
create new real-time information about the process. In particular, the review
assesses these possibilities from an industrial perspective, including sensor
performance, information value and production economy. The capabilities of
existing analytical on-line techniques are scrutinized in view of their
usefulness in soft sensor setups and in relation to typical needs in
bioprocessing in general. The review concludes with specific recommendations for
further development of soft sensors for the monitoring and control of upstream
bioprocessing.
PMID- 28423946
TI - Tween 80 surfactant-enhanced bioremediation: toward a solution to the soil
contamination by hydrophobic organic compounds.
AB - The occurrence of hydrophobic organic compounds (HOCs) in the soil has become a
highly significant environmental issue. This problem has been exacerbated by the
strong sorption of HOCs to the soils, which makes them unavailable for most
remediation processes. More and more works show that surfactant-enhanced
biological technologies offer a great potential to clear up HOCs-contaminated
soils. This article is a critical review of HOCs removal from soils using Tween
80 (one of the mostly used nonionic surfactants) aided biological remediation
technologies. The review begins with a discussion of the fundamentals of Tween 80
enhanced desorption of HOCs from contaminated soils, with special emphasis on the
biotoxicity of Tween 80. Successful results obtained by Tween 80-enhanced
microbial degradation and phytoremediation are documented and discussed in
section 3 and section 4, respectively. Results show Tween 80-enhanced
biotechnologies are promising for treating HOCs-contaminated soils. However,
considering the fact that most of these scientific studies have only been
conducted at the laboratory-scale, many improvements are required before these
technologies can be scaled up to the full-scale level. Moreover, further research
on mechanisms related to the interaction of Tween 80 with degrading
microorganisms and the plants is in high demand.
PMID- 28423947
TI - Metabolic engineering strategies for acetoin and 2,3-butanediol production:
advances and prospects.
AB - Acetoin and 2,3-butanediol (2,3-BD) have a large number of industrial
applications. The production of acetoin and 2,3-BD has traditionally relied on
oil supplies. Microbial production of acetoin and 2,3-BD will alleviate the
dependence on oil. Acetoin and 2,3-BD are neighboring metabolites in the 2,3-BD
metabolic pathway of bacteria. This review summarizes metabolic engineering
strategies for improvement of microbial acetoin and 2,3-BD production. We also
propose enhancements to current acetoin and 2,3-BD production strategies, by
offering a metabolic engineering approach that is guided by systems biology and
synthetic biology.
PMID- 28423948
TI - Fermentation at non-conventional conditions in food- and bio-sciences by the
application of advanced processing technologies.
AB - The interest in improving the yield and productivity values of relevant microbial
fermentations is an increasingly important issue for the scientific community.
Therefore, several strategies have been tested for the stimulation of microbial
growth and manipulation of their metabolic behavior. One promising approach
involves the performance of fermentative processes during non-conventional
conditions, which includes high pressure (HP), electric fields (EF) and
ultrasound (US). These advanced technologies are usually applied for microbial
inactivation in the context of food processing. However, the approach described
in this study focuses on the use of these technologies at sub-lethal levels,
since the aim is microbial growth and fermentation under these stress conditions.
During these sub-lethal conditions, microbial strains develop specific genetic,
physiologic and metabolic stress responses, possibly leading to fermentation
products and processes with novel characteristics. In some cases, these
modifications can represent considerable improvements, such as increased yields,
productivities and fermentation rates, lower accumulation of by-products and/or
production of different compounds. Although several studies report the successful
application of these technologies during the fermentation processes, information
on this subject is still scarce and poorly understood. For that reason, the
present review paper intends to assemble and discuss the main findings reported
in the literature to date, and aims to stimulate interest and encourage further
developments in this field.
PMID- 28423949
TI - Intranasal chitosan-g-HPbetaCD nanoparticles of efavirenz for the CNS targeting.
AB - Incompetence of antiretrovirals (ARV) in complete eradication of HIV from the CNS
is the biggest issue in neuro-AIDS treatment. The ineffectiveness is largely due
to the poor penetration of ARV. Hence, the present study is attempted to enhance
the CNS uptake of efavirenz (EFV) by designing intranasal EFV nanoparticles (EFV
NPs). EFV-NPs were fabricated using chitosan-g-HPbetaCD by ionic gelation method
and optimized using quadratic response surface methodology (RSM) employing two
factor, five-level circumscribed central composite design. NPs containing drug:
polymer ratio (1.25:0.79) were spherical with 198 +/- 4.4 nm size, 23.28 +/- 1.5%
drug loading and 38 +/- 1.43% entrapment efficiency. NPs showed sustained drug
release (99.03 +/- 0.30% in 8 h) and followed Fickian diffusion mechanism. It
gave 4.76 times greater permeability than plain drug solution through porcine
nasal mucosa. Enhanced CNS bioavailability (12.40-fold that of i.v solution) of
EFV, high drug-targeting percentage (99.24%) and drug-targeting index (141.3)
post-intranasal administration of NPs was observed. These results are
corroborated by gamma scintigraphy images, which revealed high CNS uptake. NPs
appeared histocompatible with porcine nasal mucosa and non-toxic to L929 cell
line. Thus, CS-g-HPbetaCD served as a potential carrier in developing intranasal
mucoadhesive EFV-NPs for the CNS targeting.
PMID- 28423951
TI - Preparation, characterization and dynamical mechanical properties of dextran
coated iron oxide nanoparticles (DIONPs).
AB - Dextran-coated iron oxide nanoparticles (DIONPs) with appropriate surface
chemistry exhibit many interesting properties that can be exploited in a variety
of biomedical applications such as magnetic resonance imaging (MRI) contrast
enhancement, tissue repair, hyperthermia, drug delivery and in cell separation.
This paper reports the experimental detail for preparation, characterization and
investigation of thermal and dynamical mechanical characteristics of the dextran
coated Fe3O4 magnetic nanoparticles. In our work, DIONPs were prepared in a 1:2
ratio of Fe(II) and Fe(III) salt in the HCl solution with NaOH at given
temperature. The obtained dextran-coated iron-oxide nanoparticles structure
property correlation was characterized by spectroscopic methods; attenuated total
reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and XRD. Coating
dextran on the iron-oxide proof of important peaks can be seen from the ATR-FTIR.
Dramatic crystallinity increment can be observed from the XRD pattern of the iron
oxide dextran nanoparticles. The thermal analysis was examined by differential
scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and differential
thermal analysis (DTA). Dynamical mechanical properties of dextran nanoparticles
were analysed by dynamic mechanical analysis (DMA). Thermal stability of the iron
oxide dextran nanoparticles is higher than that of the dextran.
PMID- 28423950
TI - Hepatoprotective and free radical scavenging actions of quercetin nanoparticles
on aflatoxin B1-induced liver damage: in vitro/in vivo studies.
AB - The objective of present study was in vitro and in vivo evaluation of
hepatoprotective and antioxidant activity of Quercetin nanoparticles (Q NPs)
against toxicity induced by aflatoxin B1. The Q NPs were prepared using
precipitation method. Hepatocytes were prepared by the method of collagenase
enzyme perfusion via portal vein. The NPs were characterized in terms of size and
morphology using dynamic light scattering (DLS) and transmission electron
microscopy (TEM), respectively. The level of parameters, such as cell death, ROS
formation, lipid peroxidation, mitochondrial membrane potential and cellular
glutathione (GSH) content, in the aflatoxin B1-treated and non-treated
hepatocytes were determined and the mentioned markers were assessed in the
presence of Q NPs. The prepared NPs showed particle size of 52.70 nm with
polydispersity index (PDI) of 0.18. In contrast to free Q, the administration of
Q NPs more efficiently decreased the rate of ROS formation, lipid peroxidation
and improved cell viability, mitochondrial membrane potential and glutathione
level and showed a significant hepatoprotective efiect by reducing levels of
aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. It
is suggested that the Q NPs is a promising candidate for drug delivery, which
enhances the hepatoprotective effect of Q against the cytotoxic effects of
aflatoxin B1.
PMID- 28423952
TI - Advances in the research of celery, an important Apiaceae vegetable crop.
AB - Celery (Apium graveolens L.), one of the most important vegetables in Apiaceae
family, is cultivated worldwide and utilized in food and cosmetic industries
because it is an excellent source of vitamins, phenolic compounds, volatile oils
and other nutrients. Celery extracts possess various medicinal properties, such
as antibacterial, anti-inflammatory and lowering blood glucose and serum lipid
levels. With the rapid advancements in molecular biology and sequencing
technology, studies on celery have been performed. Numerous molecular markers and
regulatory genes have been discovered and applied to improve celery. Research
advances, including genetic breeding, genomics research, function genes and
chemical composition, regarding celery are reviewed in this paper. Further
exploration and application trends are briefly described. This review provides a
reference for basic and applied research on celery, an important Apiaceae
vegetable crop.
PMID- 28423953
TI - Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal
tablets prepared by direct compression.
AB - The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a
mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct
compression. Various polymerization degree and particle diameter PVAs were
investigated for their usability. The tensile strength, in vitro adhesive force,
and water absorption properties of the tablets were determined to compare the
various PVAs. The highest values of the tensile strength and the in vitro
adhesive force were observed for PVAs with a medium viscosity and small particle
size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive
tablets containing the optimal PVA were compared with carboxyvinyl polymer and
hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive
force, has a low viscosity, and resulted in relatively rapid drug release.
Formulations containing carboxyvinyl polymer had high tensile strengths but short
disintegration times. Higher hydroxypropyl cellulose concentration formulations
had good adhesion forces and very long disintegration times. We identified the
optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets
containing this PVA was suggested from their formulation properties.
PMID- 28423954
TI - The design and scale-up of spray dried particle delivery systems.
AB - INTRODUCTION: The rising demand for pharmaceutical particles with tailored
physicochemical properties has opened new markets for spray drying especially for
solubility enhancement, improving inhalation medicines and stabilization of
biopharmaceuticals. Despite this, the spray drying literature is scattered and
often does not address the principles underpinning robust development of
pharmaceuticals. It is therefore necessary to present clearer picture of the
field and highlight the factors influencing particle design and scale-up. Areas
covered: The review presents a systematic analysis of the trends in development
of particle delivery systems using spray drying. This is followed by exploring
the mechanisms governing particle formation in the process stages. Particle
design factors including those of equipment configurations and feed/process
attributes were highlighted. Finally, the review summarises the current
industrial approaches for upscaling pharmaceutical spray drying. Expert opinion:
Spray drying provides the ability to design particles of the desired
functionality. This greatly benefits the pharmaceutical sector especially as
product specifications are becoming more encompassing and exacting. One of the
biggest barriers to product translation remains one of scale-up/scale-down. A
shift from trial and error approaches to model-based particle design helps to
enhance control over product properties. To this end, process innovations and
advanced manufacturing technologies are particularly welcomed.
PMID- 28423955
TI - Double ovarian stimulation (DuoStim) protocol for fertility preservation in
female oncology patients.
AB - This article describes a revised ovarian stimulation protocol (DuoStim) for
fertility preservation in female oncology patients which aims to maximise the
number of gametes obtained with subsequent improvement in cumulative birth rate,
without delaying cancer treatment. Ten patients diagnosed with malignancy between
September 2014 and October 2015 were included. The patients were treated with the
DuoStim protocol, undergoing two consecutive ovarian stimulation cycles and two
oocyte retrievals. The primary outcome was the number of oocytes collected and
vitrified during each oocyte retrieval and in total. The protocol was evaluated
regarding medical risk and patients' feedback. During the first oocyte collection
81 oocytes (61 metaphase II) were retrieved (mean = 8.1; range = 1-13) and during
the second oocyte collection 82 oocytes (67 metaphase II) were retrieved (mean=
8.2; range = 1-19). A total of 163 oocytes (128 metaphase II) were collected
(mean = 16.3; range = 6-32) and cancer treatment was not delayed for any of these
patients. There were no cases of ovarian hyperstimulation syndrome recorded. More
patients and long-term follow-up is needed to assess the efficacy and safety of
the DuoStim protocol. However, these early results are encouraging, demonstrating
an increase in number of mature oocytes retrieved during ovarian stimulation for
oncology patients, without delaying cancer treatment.
PMID- 28423956
TI - Statement of Retraction.
PMID- 28423957
TI - Trends in culprit drugs and clinical entities in cutaneous adverse drug
reactions: a retrospective study.
AB - PURPOSE: Morbidity due to cutaneous adverse drug reactions (CADRs) is quite
common. The specific culprit drugs change over time and clinicians must be kept
informed with updated knowledge, thus preventing potential CADRs. This
retrospective study is a survey of CADRs encountered in a hospital-based
population in Southern China during three time intervals, from 1984 to 2015.
MATERIALS AND METHODS: The clinical records were review of 306 patients with
CADRs who were admitted to our hospital from 2011 to 2015. These data were
compared with patients visiting our hospital during 1984-1994 and 2003-2010.
RESULTS: From 2011 to 2015, the most common CADRs were exanthematous reactions
(40.8%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; 17.0%).
There were eight cases (2.6%) of CADRs related to targeted therapy in oncology.
In the 205 CADR cases that were due to single medications, the most common
offending drugs were allopurinol (21.5%), cephalosporins (10.7%) and
carbamazepine (10.2%). The percentages of CADR cases due to allopurinol,
carbamazepine, or epidermal growth factor receptor inhibitors were significantly
higher from 2011 to 2015 compared with 1984-1994 or 2003-2010. The rate of
SJS/TEN occurrence was significantly higher in the two recent periods compared
with 1984-1994. CONCLUSIONS: Changes in drug prescriptions are a major factor
that affects the CADRs seen in clinical records. Newer drugs can be culpable for
CADRs, and more CADRs are now documented with increased severity at clinical
presentation. Reliable screening tests for specific drugs are urgently required
to eliminate possible fatalities.
PMID- 28423958
TI - Strategies and perspectives of assembling multi-enzyme systems.
AB - Multi-enzyme complexes have the potential to achieve high catalytic efficiency
for sequence reactions due to their advantages in eliminating product inhibition,
facilitating intermediate transfer and in situ regenerating cofactors.
Constructing functional multi-enzyme systems to mimic natural multi-enzyme
complexes is of great interest for multi-enzymatic biosynthesis and cell-free
synthetic biotransformation, but with many challenges. Currently, various
assembly strategies have been developed based on the interaction of
biomacromolecules such as DNA, peptide and scaffolding protein. On the other
hand, chemical-induced assembly is based on the affinity of enzymes with small
molecules including inhibitors, cofactors and metal ions has the advantage of
simplicity, site-to-site oriented structure control and economy. This review
summarizes advances and progresses employing these strategies. Furthermore,
challenges and perspectives in designing multi-enzyme systems are highlighted.
PMID- 28423959
TI - Diabetic pregnancy, maternal and fetal docosahexaenoic acid: a review of existing
evidence.
AB - OBJECTIVE: Docosahexaenoic acid (DHA) is vital for fetal development especially
during the third trimester of gestation when the speed of fetal brain growth is
at its peak. Diabetes modifies the maternal fatty acid profile, which may in turn
change the quantity and/or quality of lipids transferred to the fetus. Neonates
born to diabetic mothers might be more vulnerable to DHA deficiency leading to
lower cognitive scores together with lower overall intellectual quotients when
compared to control. We reviewed the influence of type 1 or type 2 pre
gestational (PGD) and gestational diabetes mellitus (GDM) on maternal and fetal
DHA levels. METHOD: We searched MEDLINE articles about PGD and/or GDM and DHA
published before October 2016. RESULTS: Maternal blood DHA level seems higher in
those with diabetes than those without diabetes. However, DHA in cord plasma of
neonates born to PGD and/or GDM mothers seem lower compared to neonates born to
nondiabetic mothers. CONCLUSIONS: Altogether, these results suggest that the
transfer of DHA from the mother to the fetus may be deficient or dysregulated in
diabetic pregnancies. What remains to be understood is how placental lipid
transport is regulated and whether there is a link with clinical
neurodevelopmental phenotypes in the newborns.
PMID- 28423960
TI - The role of molecular diagnostic testing in the management of thyroid nodules.
AB - INTRODUCTION: Fine needle aspiration (FNA) with cytologic examination remains the
standard of care for investigation of thyroid nodules. However, as many as 30% of
FNA samples are cytologically indeterminate for malignancy, which confounds
clinical management. To reduce the burden of repeat diagnostic testing and
unnecessary surgery, there has been extensive investigation into molecular
markers that can be detected on FNA specimens to more accurately stratify a
patient's risk of malignancy. Areas covered: In this review, the authors discuss
recent evidence and progress in molecular markers used in the diagnosis of
thyroid cancer highlighting somatic gene alterations, molecular technologies and
microRNA analysis. Expert commentary: The goal of molecular markers is to improve
diagnostic accuracy and aid clinicians in the preoperative management of thyroid
lesions. Modalities such as direct mutation analysis, mRNA gene expression
profiling, next-generation sequencing, and miRNA expression profiling have been
explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no
perfect test has been discovered, molecular diagnostic testing has revolutionized
the management of thyroid nodules.
PMID- 28423962
TI - The utility of fecal calprotectin in predicting the need for escalation of
therapy in inflammatory bowel disease.
AB - BACKGROUND AND AIMS: Fecal calprotectin is an important biomarker used in the
evaluation of inflammatory bowel disease. It has proven to be an effective tool
in initial screening as well monitoring response to therapy. The aim of this
study is to examine the utility of fecal calprotectin both as a predictor for the
escalation of therapy in established inflammatory bowel disease and as a
predictor of de novo diagnosis. METHODS: Patients with signs and symptoms
concerning for inflammatory bowel disease presenting to outpatient clinics were
recruited to provide fecal calprotectin stool samples prior to endoscopic
evaluation. Patients were followed up for at least one year and monitored
clinically for any change in symptomatology, escalation of therapy or development
of IBD, confirmed endoscopically. RESULTS: A total of 126 patients, of whom 72
were known to have underlying inflammatory bowel disease, were included in the
final analysis. Among the patients with elevated fecal calprotectin levels and
known inflammatory bowel disease, 66% (33/50) went on to have escalation of
therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels
were in the normal range (p < .0001). For the remaining patients who at baseline
did not have inflammatory bowel disease and a normal endoscopic evaluation,
elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the
next 12 months. CONCLUSIONS: Fecal calprotectin is a useful test for predicting
escalation of therapy in established inflammatory bowel disease.
PMID- 28423964
TI - Corrigendum.
PMID- 28423963
TI - Patient perceptions of environmental control units: experiences of Veterans with
spinal cord injuries and disorders receiving inpatient VA healthcare.
AB - PURPOSE: To assess patients' perceptions of environmental control units (ECUs) at
Veterans Affairs Spinal Cord Injury Centers. MATERIALS AND METHODS: A brief
questionnaire was conducted with patients in real-time while they were
hospitalised ("on-the-spot questionnaire"); a survey was mailed to patients who
had recently been discharged from a hospital stay ("discharge survey"). Data were
analysed using descriptive statistics. RESULTS: Seventy on-the-spot
questionnaires and 80 discharge surveys were collected. ECU features used most
frequently were comparable in responses from both surveys: watching TV/movies
(81%, 85%), calling the nurse (68%, 61%), turning lights on/off (63%, 52%),
adjusting the bed (53%, 33%), and playing games (39%, 24%). Many on-the-spot
questionnaire respondents felt the ECU met their need for independence a great
deal (42%). Most respondents to both surveys were satisfied with the ECU (71%,
57%). Areas for improvement included user training, improved functionality of the
device and its features, and device design. CONCLUSIONS: ECUs were well-accepted
by persons with spinal cord injuries/disorders (SCI/D) in the inpatient setting,
and increased patients' perceptions of independence. To maximise usability and
satisfaction, facilities should ensure that comprehensive training on ECU use and
features available is offered to all patients, and resources are available for
timely troubleshooting and maintenance. Implications for rehabilitation An
environmental control unit (ECU) is a form of assistive technology that allows
individuals with disabilities (such as spinal cord injuries and disorders
[SCI/D]) to control functional and entertainment-related aspects of their
environment. ECU use can increase functioning, independence and psychosocial well
being among individuals with SCI/D, by allowing users to reclaim control over day
to-day activities that are otherwise limited by their disability. Our study
results indicate that, among persons with SCI/D, ECUs are well-accepted and
increase perceptions of independence. To maximise usability and patient
satisfaction, facilities should ensure that comprehensive training on how to use
ECUs and what features are available is offered to all patients, and resources
are available for timely troubleshooting and maintenance.
PMID- 28423965
TI - Historical mitochondrial diversity in African leopards (Panthera pardus) revealed
by archival museum specimens.
AB - Once found throughout Africa and Eurasia, the leopard (Panthera pardus) was
recently uplisted from Near Threatened to Vulnerable by the International Union
for the Conservation of Nature (IUCN). Historically, more than 50% of the
leopard's global range occurred in continental Africa, yet sampling from this
part of the species' distribution is only sparsely represented in prior studies
examining patterns of genetic variation at the continental or global level. Broad
sampling to determine baseline patterns of genetic variation throughout the
leopard's historical distribution is important, as these measures are currently
used by the IUCN to direct conservation priorities and management plans. By
including data from 182 historical museum specimens, faecal samples from ongoing
field surveys, and published sequences representing sub-Saharan Africa, we
identify previously unrecognized genetic diversity in African leopards. Our mtDNA
data indicates high levels of divergence among regional populations and strongly
differentiated lineages in West Africa on par with recent studies of other large
vertebrates. We provide a reference benchmark of genetic diversity in African
leopards against which future monitoring can be compared. These findings
emphasize the utility of historical museum collections in understanding the
processes that shape present biodiversity. Additionally, we suggest future
research to clarify African leopard taxonomy and to differentiate between
delineated units requiring monitoring or conservation action.
PMID- 28423966
TI - Linear energy transfer distributions in the brainstem depending on tumour
location in intensity-modulated proton therapy of paediatric cancer.
AB - BACKGROUND: For tumours near organs at risk, there is concern about unintended
increase in biological dose from elevated linear energy transfer (LET) at the
distal end of treatment fields. The objective of this study was therefore to
investigate how different paediatric posterior fossa tumour locations impact LET
and biological dose to the brainstem during intensity-modulated proton therapy
(IMPT). MATERIAL AND METHODS: Multiple IMPT plans were generated for four
different simulated tumour locations relative to the brainstem for a five-year
old male patient. A prescribed dose of 59.4 Gy(RBE) was applied to the planning
target volumes (PTVs). Plans with two lateral and one posterior non-coplanar
fields were created, along with plans with modified field arrangements. The dose
averaged LET (LETd) and the physical dose * RBELET (D * RBELET), where RBELET=1+c
* LETd, were calculated using the FLUKA Monte Carlo code. A scaling parameter c
was applied to make the RBELET represent variations in the biological effect due
to LET. RESULTS: High LETd values surrounded parts of the PTV and encompassed
portions of the brainstem. Mean LETd values in the brainstem were 3.2-6.6
keV/MUm. The highest absolute brainstem LETd values were seen with the tumour
located most distant from the brainstem, whereas lower and more homogeneous LETd
values were seen when the tumour invaded the brainstem. In contrast, the highest
mean D * RBELET values were found in the latter case (54.0 Gy(RBE)), while the
case with largest distance between tumour and brainstem had a mean D * RBELET of
1.8 Gy(RBE). CONCLUSIONS: Using IMPT to treat posterior fossa tumours may result
in high LETd values within the brainstem, particularly if the tumour volume is
separated from the brainstem. However, the D * RBELET was greater for tumours
that approached or invaded the brainstem. Changing field angles showed a
reduction of LETd and D * RBELET in the brainstem.
PMID- 28423967
TI - Identifying selectively important amino acid positions associated with
alternative habitat environments in fish mitochondrial genomes.
AB - Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to
develop genetic adaptations to alternative environment factors, especially
salinity. Functional consequences of the protein variations associated with
habitat environments in fish mitochondrial genomes have not yet received much
attention. We analyzed 829 complete fish mitochondrial genomes and compared the
amino acid differences of 13 mitochondrial protein families between FW and SW
fish groups. We identified 47 specificity determining sites (SDS) that associated
with FW or SW environments from 12 mitochondrial protein families. Thirty-two
(68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining
sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored
as probably damaging to the protein structures. Furthermore, phylogenetic tree
based Bayes Empirical Bayes analysis also detected 63 positive sites associated
with alternative habitat environments across ten mtDNA proteins. These signatures
could be important for studying mitochondrial genetic variation relevant to fish
physiology and ecology.
PMID- 28423968
TI - Penetrating brain injury with a metal bar and a knife: Report of two interesting
cases.
AB - Introduction Penetrating brain injury (PBI) is uncommon among the civilian
population. Here, we report two interesting cases of PBI. Case presentation The
first patient was a 20-year-old male who sustained a penetrating head injury with
a metal bar during an accident at work. The patient underwent early surgical
intervention, and related meningitis was treated with antibiotics. The patient
was discharged 45 days later with no deficit. The second patient was a 34-year
old male who was the victim of a violence attack and was admitted to hospital. He
was struck by a knife to his right temporal bone. A brain computed tomography
scan and magnetic resonance imaging (MRI) demonstrated the tract of the knife
within the brain parenchyma. The patient underwent conservative treatment. After
several weeks, the patient was discharged in good health. Conclusion Although
severe PBI has a poorer prognosis than a blunt brain injury, in treating of these
patients, aggressive and timely surgical intervention, proper wide-spectrum
antibiotic administration, stringent and diligent care in the intensive-care unit
and careful management of the associated complications are mandated.
PMID- 28423970
TI - Recent advances on topical antimicrobials for skin and soft tissue infections and
their safety concerns.
AB - Antimicrobial resistance of disease-related microorganisms is considered a
worldwide prevalent and serious issue which increases the failure of treatment
outcomes and leads to high mortality. Considering that the increased resistance
to systemic antimicrobial therapy often needs of the use of more toxic agents,
topical antimicrobial therapy emerges as an attractive route for the treatment of
infectious diseases. The topical antimicrobial therapy is based on the absorption
of high drug doses in a readily accessible skin surface, resulting in a reduction
of microbial proliferation at infected skin sites. Topical antimicrobials retain
the following features: (a) they are able to escape the enzymatic degradation and
rapid clearance in the gastrointestinal tract or the first-pass metabolism during
oral administration; (b) alleviate the physical discomfort related to intravenous
injection; (c) reduce possible adverse effects and drug interactions of systemic
administrations; (d) increase patient compliance and convenience; and (e) reduce
the treatment costs. Novel antimicrobials for topical application have been
widely exploited to control the emergence of drug-resistant microorganisms. This
review provides a description of antimicrobial resistance, common microorganisms
causing skin and soft tissue infections, topical delivery route of
antimicrobials, safety concerns of topical antimicrobials, recent advances,
challenges and future prospective in topical antimicrobial development.
PMID- 28423969
TI - Process Evaluation of the Type 2 Diabetes Mellitus PULSE Program Randomized
Controlled Trial: Recruitment, Engagement, and Overall Satisfaction.
AB - BACKGROUND: Men are underrepresented in weight loss and type 2 diabetes mellitus
(T2DM) prevention studies. PURPOSE: To determine the effectiveness of
recruitment, and acceptability of the T2DM Prevention Using LifeStyle Education
(PULSE) Program-a gender-targeted, self-administered intervention for men.
METHODS: Men (18-65 years, high risk for T2DM) were randomized to intervention (
n = 53) or wait-list control groups ( n = 48). The 6-month PULSE Program
intervention focused on weight loss, diet, and exercise for T2DM prevention. A
process evaluation questionnaire was administered at 6 months to examine
recruitment and selection processes, and acceptability of the intervention's
delivery and content. Associations between self-monitoring and selected outcomes
were assessed using Spearman's rank correlation. RESULTS: A pragmatic recruitment
and online screening process was effective in identifying men at high risk of
T2DM (prediabetes prevalence 70%). Men reported the trial was appealing because
it targeted weight loss, T2DM prevention, and getting fit, and because it was
perceived as "doable" and tailored for men. The intervention was considered
acceptable, with men reporting high overall satisfaction (83%) and engagement
with the various components. Adherence to self-monitoring was poor, with only 13%
meeting requisite criteria. However, significant associations were observed
between weekly self-monitoring of weight and change in weight ( rs = -.47, p =
.004) and waist circumference ( rs = -.38, p = .026). Men reported they would
have preferred more intervention contact, for example, by phone or email.
CONCLUSIONS: Gender-targeted, self-administered lifestyle interventions are
feasible, appealing, and satisfying for men. Future studies should explore the
effects of additional non-face-to-face contact on motivation, accountability,
self-monitoring adherence, and program efficacy.
PMID- 28423971
TI - Intrauterine infection, immune system and premature birth.
AB - Preterm birth accounts for nearly one million deaths among children under five
years of age, and although its etiopathogenesis is not fully elucidated,
ascending intrauterine infection and fetal inflammatory response seem to be the
main triggers. The intense inflammatory response mediated by IL-1beta, TNF-alpha,
PAF, IFN-gamma and IL-6, PGE2 and MMP-1 and MMP-9 causes fetal membrane damage
and rupture, increased uterine contractions and biochemical and structural
changes in the cervix. Furthermore, preterm neonates have deficient innate and
adaptive immune responses characterized by reduced levels of IgG, opsonization
and phagocytosis, as well as increased activation of Th1 cells in relation to Th2
cells. Therefore, this triad is favors the occurrence of neonatal complications,
such as respiratory distress syndrome, necrotizing enterocolitis, retinopathy of
prematurity and bronchopulmonary dysplasia. Due to serious maternal and child
health complications of intrauterine infection, several studies have tried to
identify biomarkers for the early diagnosis of this entity. This literature
review aims to discuss the main scientific findings regarding the association
between ascending intrauterine infection, immune system and preterm birth.
PMID- 28423972
TI - Sexual Function and Testosterone Level in Men With Conservatively Treated Chronic
Kidney Disease.
AB - Sexual dysfunctions are common, but underrecognized, in patients with chronic
kidney disease (CKD) and are inversely associated with the glomerular filtration
rate (GFR). Sexual dysfunctions may affect quality of life in males with CKD. The
aim of this study was to analyze the relationship among sex hormones, sexual
function, and sexual satisfaction in a group of men between 18 and 50 years of
age with CKD Stages 1 to 5 not treated with hemodialysis or peritoneal dialysis.
Fasting blood samples for hemoglobin, testosterone, prolactin, and luteinizing
hormone and questionnaire surveys (Sexual Complaints Screener for Men,
International Index of Erectile Function, and Aging Male Symptom scale) were
evaluated in 100consecutive men. Higher CKD stage (i.e., lower renal function)
had a statistically significant ( p < .01) correlation with lower total
testosterone, free testosterone, and hemoglobin levels, and higher luteinizing
hormone and prolactin levels. Sexual function/dysfunctions were not significantly
associated with CKD stage, even after adjustment for age and serum testosterone.
The results indicate that CKD stage is a factor affecting testosterone levels in
combination with age in men between 18 and 50 years of age at different stages of
CKD but not treated with hemodialysis or peritoneal dialysis. Sexual dysfunctions
are common but not strongly correlated to testosterone levels, prolactin levels,
and survey (Sexual Complaints Screener for Men, International Index of Erectile
Function, and Aging Male Symptom scale) responses in patients with CKD.
PMID- 28423973
TI - Neurological involvement of IgG4-related disease: description of a case and
review of the literature.
AB - IgG4-related disease is a recently discovered pathological entity, histologically
characterised by fibrosis and IgG4-positive plasma cell infiltration. This
condition may virtually involve every site of the organism, with a various range
of clinical presentations. The most commonly affected organ is the pancreatic
gland, but it can also involve the biliary tract, salivary and lacrimal glands,
kidneys, orbital tissues, lymph nodes, lungs and many others. More recently, IgG4
related disease has been demonstrated to involve, in rare cases, also the central
nervous system, with a pattern mainly characterised by hypertrophic
pachymeningitis. In this paper we evaluated the clinical and magnetic resonance
imaging features of the IgG4-related disease in the central nervous system,
reporting a case of brain and spinal cord involvement. In our case, in fact, a 62
year-old man complaining of paresthesia, burning dysesthesia and severe
hyposthenia in the lower limbs presented with inflammatory pseudotumour with
orbital involvement and focal dural and spinal root thickening.
PMID- 28423974
TI - Competitive bass anglers: a new concern in sports medicine.
AB - OBJECTIVE: Competitive bass angling involves sport fishing against other anglers
while targeting a species of fish known as the black basses. Due to the rapidly
growing popularity of high school competitive bass angling in Alabama and the
nature of the casting motion similar to that of overhead athletes, we sought to
examine the prevalence of sports type injuries in this population. METHODS: In
spring 2016, an anonymous survey was distributed across two large scale
competitive high school fishing tournaments, allowing for a broad sampling of
anglers throughout the state of Alabama. Survey items included demographic
information, relevant past medical history, and various pains associated with the
shoulder, elbow and wrist. Results were recorded and analyzed electronically
using Microsoft Excel and IBM SPSS statistical software. RESULTS: A total of 257
surveys were recorded. The response rate was 61%. The mean age of participating
anglers was 15 +/- 1.61 years. The majority (42%) of anglers fished year round.
On average, anglers casted nearly 1,000 more times while competing versus fishing
recreationally. Approximately 15% of anglers experienced shoulder, elbow, and
wrist pain. The most common factors associated with pain included higher
tournament cast counts, number of competitive years, number of tournaments/year,
number of tournaments, and use of light weight lures. CONCLUSION: A large portion
of high school competitive anglers experience upper extremity pain. Knowledge of
angling factors associated with pain allow for the creation of a modifiable
routine to help reduce pain in affected anglers and prevent pain in healthy
anglers.
PMID- 28423976
TI - Screening for Dyslexia in French-Speaking University Students: An Evaluation of
the Detection Accuracy of the Alouette Test.
AB - Developmental dyslexia is a lifelong impairment affecting 5% to 10% of the
population. In French-speaking countries, although a number of standardized tests
for dyslexia in children are available, tools suitable to screen for dyslexia in
adults are lacking. In this study, we administered the Alouette reading test to a
normative sample of 164 French university students without dyslexia and a
validation sample of 83 students with dyslexia. The Alouette reading test is
designed to screen for dyslexia in children, since it taps skills that are
typically deficient in dyslexia (i.e., phonological skills). However, the test's
psychometric properties have not previously been available, and it is not
standardized for adults. The results showed that, on the Alouette test, dyslexic
readers were impaired on measures of accuracy, speed, and efficiency
(accuracy/reading time). We also found significant correlations between the
Alouette reading efficiency and phonological efficiency scores. Finally, in terms
of the Alouette test, speed-accuracy trade-offs were found in both groups, and
optimal cutoff scores were determined with receiver operator characteristic
curves analysis, yielding excellent discriminatory power, with 83.1% sensitivity
and 100% specificity for reading efficiency. Thus, this study supports the
Alouette test as a sensitive and specific screening tool for adults with
dyslexia.
PMID- 28423975
TI - Turning Points in the Lives of Youth of With/Without ADHD: Are They Linked to
Changes in Substance Use?
AB - OBJECTIVE: This study examines the behavior beliefs, social supports, and turning
points in individuals with/without ADHD related to their substance use/abuse
(SU/A) decisions. METHOD: The coded interviews from 60 participants with/without
ADHD were compared for their SU/A decisions and precipitants with these decisions
among abstainers, persisters, and desisters. RESULTS: ADHD participants reported
fewer social advantages to avoid SU/A than non-ADHD participants. Desisters and
persisters reported more social advantages of using drugs than abstainers.
Persisters reported both more negative and positive psychological/physiological
effects of SU/A. ADHD participants reported fewer positive role models in their
lives. Non-ADHD patients reported more positive turning points than ADHD
participants, regardless of SU/A status. CONCLUSION: ADHD individuals face
challenges in making healthy decisions about SU/A due to lack of positive role
models. Reinforcing accurate behavioral beliefs may be important to change
behaviors in individuals with SU/A or to prevent SU/A initiation in ADHD
individuals.
PMID- 28423977
TI - Age-associated differences in motor output variability and coordination during
the simultaneous dorsiflexion of both feet.
AB - Older adults are more variable than young adults on tasks that demand the
simultaneous control of more than one effector, and the difference between age
groups may be related to their different capacity of coordinating the force
output of the involved effectors. The goal of this study was to determine whether
age-associated differences in motor output variability during tasks involving the
simultaneous dorsiflexion of two feet can be partially explained by differences
in coordination and possibly attenuated by physical training. Ten young and 22
old adults (10 trained and 12 untrained old adults) volunteered to participate in
the study. Trained older adults had experience in a high-intensity mixed modality
training (MMT) regime for a minimum of 1 year. Volunteers performed successive
trials of a constant force task and a goal-directed task, with and without visual
feedback. Within- and between-trial variability were calculated and coordination
was quantified using the uncontrolled manifold (UCM) approach (i.e., co-variation
of the force outputs of both feet were used to quantify a motor synergy index).
Older adults exhibited greater variability and lower synergy (p < .05),
independently of physical training status, than young adults. Removal of visual
feedback caused greater variability and lower synergy for all groups (p < .05).
Our results suggest that older adults exhibit greater motor output variability in
tasks involving the simultaneous dorsiflexion of both feet possibly due to a lack
of coordination between the feet.
PMID- 28423978
TI - Reward Processing Deficits During a Spatial Attention Task in Patients With ADHD:
An fMRI Study.
AB - OBJECTIVE: In this study, we aimed to explore how cues signaling rewards and
feedbacks about rewards are processed in ADHD. METHOD: Inside the scanner, 16
healthy children and 19 children with ADHD completed a spatial attention paradigm
where cues informed about the availability of reward and feedbacks were provided
about the earned reward. RESULTS: In ventral anterior thalamus (VA), the controls
exhibited greater activation in response to reward-predicting cues, as compared
with no-reward cues, whereby in the ADHD group, the reverse pattern was observed
(nonreward > reward). For feedbacks; absence of rewards produced greater
activation than presence in the left caudate and frontal eye field for the
control group, whereas for the ADHD group, the reverse pattern was again observed
(reward > nonreward). DISCUSSION: The present findings indicate that ADHD is
associated with difficulty integrating reward contingency information with the
orienting and regulatory phases of attention.
PMID- 28423979
TI - Pregnancy-associated plasma protein-A truncation limits in antenatal screening
for trisomy 18.
AB - Upper and lower truncation limits are commonly applied to quantitative markers
used in medical screening tests. We here examine data on 375 trisomy 18 and
522,081 unaffected singleton pregnancies, to determine if the lower truncation
limit should be set below the previously specified 0.2 multiples of the median. A
lower truncation limit of 0.15 would reduce the underestimation of the risk of
having a trisomy 18 pregnancy in about 50% of affected pregnancies and would lead
to an estimated 10 percentage point increase in the detection rate, with only a
very small increase in the false-positive rate.
PMID- 28423980
TI - Multiple myeloma of the spine.
AB - Radiology provides a crucial clinical adjunct in patients with plasma cell
disorders, in particular multiple myeloma, and its uses are evolving and
expanding. This pictorial review illustrates the role of imaging throughout the
patient's clinical course, with specific reference to recently updated
international diagnostic criteria. At presentation, imaging optimises
characterisation and staging of the plasma-cell disorder, while later in the
course of the disease, its roles include the monitoring of disease progression,
assessment of post-treatment response and the investigation of clinical
deterioration.
PMID- 28423981
TI - Post-partum follow-up of women with gestational diabetes mellitus: effectiveness,
determinants, and barriers.
AB - BACKGROUND: Despite the recommendations for postpartum blood glucose monitoring
post gestational diabetes mellitus (GDM); scientific evidence reveals that these
recommendations may not be fully complied to. This study aimed to follow-up women
up to 2 years post-delivery with pregnancies complicated by GDM and healthy
controls to assess this fact. METHODS: Women with GDM (n = 78) and normal glucose
tolerant (n = 89) delivered in 2014 were followed up for 2 years. They were
informed and enquired via telephone about their blood glucose screening, physical
activity, postpartum complications, and current weight status of mother and baby.
RESULTS: Women with previous GDM were older and reported higher body weight 2
years post-delivery. At the 2 year follow-up, n = 11 (14.1%) participants had
developed diabetes, all with previous GDM. Both weight at birth (3.8 +/- 0.5 kg)
and at 2-year (10.7 +/- 2.3 kg) for the babies born to GDM mothers was
significantly higher than the NGT group babies (2.6 +/- 0.63 and 7.1 +/- 1.4 kg;
p < .05). Only 27 women regularly opted for T2DM screening via monitoring blood
glucose or HbA1c levels postpartum. The top reason for failed screening included:
believing that GDM would disappear after delivery, and being occupied with the
baby. CONCLUSIONS: The high incidence of T2DM in women with previous GDM is an
alarming finding. Given this trend, systematic follow-up programs are needed to
reduce obesity and diabetes risk.
PMID- 28423982
TI - From Data to Improved Decisions: Operations Research in Healthcare Delivery.
AB - BACKGROUND: The Operations Research Interest Group (ORIG) within the Society of
Medical Decision Making (SMDM) is a multidisciplinary interest group of
professionals that specializes in taking an analytical approach to medical
decision making and healthcare delivery. ORIG is interested in leveraging
mathematical methods associated with the field of Operations Research (OR) to
obtain data-driven solutions to complex healthcare problems and encourage
collaborations across disciplines. This paper introduces OR for the non-expert
and draws attention to opportunities where OR can be utilized to facilitate
solutions to healthcare problems. METHODS: Decision making is the process of
choosing between possible solutions to a problem with respect to certain metrics.
OR concepts can help systematically improve decision making through efficient
modeling techniques while accounting for relevant constraints. Depending on the
problem, methods that are part of OR (e.g., linear programming, Markov Decision
Processes) or methods that are derived from related fields (e.g., regression from
statistics) can be incorporated into the solution approach. This paper highlights
the characteristics of different OR methods that have been applied to healthcare
decision making and provides examples of emerging research opportunities.
EXAMPLES: We illustrate OR applications in healthcare using previous studies,
including diagnosis and treatment of diseases, organ transplants, and patient
flow decisions. Further, we provide a selection of emerging areas for utilizing
OR. CONCLUSIONS: There is a timely need to inform practitioners and policy makers
of the benefits of using OR techniques in solving healthcare problems. OR methods
can support the development of sustainable long-term solutions across disease
management, service delivery, and health policies by optimizing the performance
of system elements and analyzing their interaction while considering relevant
constraints.
PMID- 28423984
TI - Congenital amelanotic melanoma in a crossbred heifer calf.
AB - A large, pedunculated cutaneous mass protruding from the left flank fold and an
enlarged left prefemoral lymph node were found on examination of a 3-d-old
crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral
lymphadenopathy, and the mass, along with the left prefemoral lymph node, was
surgically excised. Histologic examination of the mass and the lymph node
revealed a homogeneous population of neoplastic cells that stained positively
with immunohistochemical stains S100 and melan A, supporting a diagnosis of
congenital amelanotic melanoma with nodal metastasis. Two months later, the calf
became acutely recumbent and was euthanized after clinical examination revealed
widespread metastasis. Gross autopsy revealed widely disseminated metastases that
involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa,
multiple lymph nodes, and the marrow cavity of several long bones. Our case
serves as a reminder that, although rare, congenital neoplasms occur in bovids
and have the potential for aggressive, metastatic behavior.
PMID- 28423985
TI - Anesthetic Approach for Endoscopic Repair of Acquired Tracheoesophageal Fistula.
AB - Tracheoesophageal fistula develops in 5 % to 15 % of patients with esophageal
cancer. Metal stent placement can be used for treatment. Stent placement can
result in aspiration, hemorrhage, perforation, migration, and pneumonia. Patients
may present for medical attention with unanticipated worsening of the fistula and
stent displacement requiring special anesthetic care. We discuss the
perianesthetic management of a patient with malignant tracheoesophageal fistula
and stent migration who presented for endoscopic esophageal stent replacement.
PMID- 28423986
TI - Global longitudinal strain from resting echocardiogram is associated with long
term adverse cardiac outcomes in patients with suspected coronary artery disease.
AB - PURPOSE: Measuring myocardial strain using two-dimensional speckle tracking
echocardiography has emerged as a new tool to identify subclinical ventricular
dysfunction. Abnormal strain has been shown to have superior sensitivity compared
with dobutamine stress echocardiography for viability assessment; however, there
is a paucity of data regarding the prediction of long-term major adverse cardiac
events. We compared the prognostic ability of both global longitudinal strain
(GLS) from resting echocardiograms to regional wall motion score index (WMSI)
from stress echocardiograms in their ability to predict long-term major adverse
cardiac events. METHODS: Patients referred for stress echocardiography, who also
underwent coronary angiography within 3 months of stress echo (n=122), were
enrolled. Patients with reduced ejection fractions (<40%) were excluded. Patients
were followed for a median of 3.4 years for major adverse cardiac events,
readmissions and repeat cardiac testing. RESULTS: Patients with abnormal GLS (GLS
<16.8%) from the resting echocardiogram obtained as part of the exercise
echocardiogram experienced a significantly shorter time to major adverse cardiac
events (p=0.026), first cardiovascular hospitalization and repeat cardiac testing
(p=0.0011) compared to those with normal GLS. Abnormal GLS appears to be a better
predictor than abnormal WMSI in predicting major adverse cardiac events (p=0.174)
and time to first cardiovascular hospitalization or repeat cardiac testing
(p=0.0093). CONCLUSION: GLS may be a better predictor of long-term major adverse
cardiac events, readmissions and repeat cardiac testing than WMSI in patients
undergoing stress echocardiography.
PMID- 28423987
TI - Reproducibility of upper leg EMG frequency content during cycling.
AB - Reproducibility of frequency content from surface electromyography (sEMG) signals
has not been assessed and it is unknown if incremental load testing design could
affect sEMG in cycling. The goals of this study were to assess the
reproducibility of measures from sEMG frequency content between sessions and to
compare these frequency components between a ramp and a step incremental cycling
test. Eighteen cyclists performed four incremental load cycling tests to
exhaustion. Two tests were performed using a step increment (load started at 100
W for 3 min followed by increments of 30 W every 3 min) and two were performed
using a ramp increment (load started at 100 W for 1 min followed by increments of
30 W.min-1). sEMG was monitored bilaterally for the rectus femoris and vastus
lateralis throughout the tests and converted into overall activation (whole
signal bandwidth), high- and low-frequency contents. The reproducibility of the
frequency content ranged from none to strong (ICC = 0.07-0.90). Vastus lateralis
activation was larger at the step compared to the ramp test (P < 0.01), without
differences for rectus femoris (P = 0.22-0.91) and for the high-frequency (P =
0.28-0.95) and low-frequency contents (P = 0.13-0.94). sEMG from vastus lateralis
and rectus femoris presented none to strong reproducibility. Vastus lateralis is
more activated in step test design.
PMID- 28423988
TI - Tumor collision of uterine adenocarcinoma and leiomyosarcoma in a goat.
AB - An aged mixed-breed goat doe was presented with a 9-mo history of serosanguineous
vaginal discharge. Vaginal speculum examination revealed serosanguineous
discharge but otherwise no abnormalities. Transrectal ultrasonography showed
normal ovaries and multifocal cystic lesions within the uterus.
Ovariohysterectomy was recommended because of a strong suspicion of neoplasia.
Multiple, non-resectable masses were noted in and around the uterus
intraoperatively, and euthanasia was elected. Autopsy revealed multiple masses
within the uterus, cervix, and lung parenchyma. Histologically, the masses within
the uterus represented a likely collision tumor of primary adenocarcinoma and
leiomyosarcoma. Our report highlights the importance of obtaining biopsy samples
of all masses because the lesions described showed significantly different
biological behavior. This information is vital to guide treatment and prognosis.
PMID- 28423989
TI - Outbreaks of bovine herpesvirus 2 infections in calves causing ear and facial
skin lesions.
AB - We describe 3 outbreaks of superficial dermatitis caused by bovine herpesvirus 2
(BoHV-2) in dairy breed calves. Clinically, all of the affected calves were 12-26
d of age, had alopecia and crusts on the face and ears, and were non-pruritic and
afebrile. Affected animals recovered spontaneously without any treatment within 2
4 wk after onset of clinical signs based on 1 herd with follow up. Histologic
examination of all skin crust or tissue samples identified neutrophilic
inflammation, mild hyperkeratosis, multinucleate syncytial cells, and
intranuclear inclusion bodies in the syncytial cells. Real-time PCR testing on
affected surface crusts or tissue provided evidence of BoHV-2, and testing, where
performed, was negative for parapoxvirus including bovine papular stomatitis
virus and the ovine form of malignant catarrhal fever tested in EDTA blood
samples. Bovine viral diarrhea virus also was negative by ELISA, as well as
bovine herpesvirus 1 by immunohistochemistry. Direct electron microscopy of
infected tissues in the first outbreak revealed herpesvirus-like particles.
PMID- 28423990
TI - Self-assembled nanogel of cholesterol-bearing xyloglucan as a drug delivery
nanocarrier.
AB - Xyloglucan (XG) is a multibranched polysaccharide consisting of a main chain beta
1,4-glucan with xylose and galactose side chains. In this study, cholesterol
bearing XG (CHXG) was synthesized by the reaction of XG with cholesteryl N-(6
isocyanatohexyl) carbamate. The CHXG molecules self-assembled in water to form
nanogels consisting of about 100 molecules of XG, and were characterized using
light scattering and transmission electron microscopy. The number of cholesteryl
groups per physical cross-linking site was estimated using a fluorescence
quenching method. The resulting CHXG nanogels could be complexed with molecules
of low molecular weight, such as iodine and paclitaxel, making the nanogels
useful as drug carriers. The CHXG nanogels could also be specifically
internalized by hepatocytes via the galactose receptors on their cell surface.
CHXG self-assembled nanogels may be suitable as novel drug nanocarriers with
galactose-specific targetability.
PMID- 28423991
TI - Changes in body mass, stature and BMI in South African elite U18 Rugby players
from different racial groups from 2002-2012.
AB - The purpose of this study was to determine whether there are differences between
racial groups for body mass, stature and body mass index (BMI) in South African
elite U18 rugby players and whether there were significant changes in these
measurements between 2002 and 2012. Self-reported body mass and stature were
obtained from U18 players (n = 4007) who attended the national tournament during
this period. BMI was calculated for each player.White players were 9.8 kg heavier
than black players, who were 2.3 kg heavier than coloured players (P < 0.0001).
The body mass of all groups increased from 2002 to 2012 (P < 0.0001). White
players were 7.0 cm taller than black players who were 0.5 cm taller than
coloured players (P < 0.0001). Players' stature measurements did not change
significantly during the study period. The average BMI of white players was 0.9
kg.m-2 greater than black players who were on average 0.7 kg.m-2 greater than
coloured players (P < 0.0001). The BMI of all groups changed similarly over the
study period. The body mass, stature and BMI of elite under-18 rugby players in
South Africa were significantly different between racial groups. This has
implications for transforming the game to make it representative of the South
African population.
PMID- 28423992
TI - Secrecy, empowerment and protection: positioning PrEP in KwaZulu-Natal, South
Africa.
AB - The release of World Health Organisation guidelines recommending the prophylactic
use of daily Truvada(r) for all populations at high risk of acquiring HIV opens
the way for implementation of oral pre-exposure prophylaxis (PrEP). The impact of
new prevention technologies is, however, dependent on demand creation strategies
such as user awareness, acceptability and access, which in turn are influenced by
sociocultural and gender norms. This study was conducted in three locations in
KwaZulu-Natal, urban, rural and peri-urban, with six participatory workshops.
Knowledge, desirable features of a product and demand positioning for PrEP were
assessed using a participatory action media research process which included art
based activities and group discussion using a semi-structured interview schedule.
The data were analysed using thematic analysis. The key themes that emerged in
relation to product adoption were: ability to maintain secrecy of product use;
the need for agency with personal choices around HIV prevention; and an increased
desire for HIV protection. Findings reaffirm the influence of user engagement in
understanding the sociocultural dynamics that influence demand creation for PrEP
adoption.
PMID- 28423993
TI - Lateralization of motor reactions and formation of behavioural tactics during
learning in the eight-arm radial maze in adolescent and adult rats.
AB - The problem of motor lateralization in ontogenesis is important for understanding
adaptation development. In our experiment adolescent (P28-P30) and adult (P120)
rats were trained in an eight-arm radial maze and their motor behaviour compared
during training. During learning, the adult rats typically started by moving
either left or right direction in the central arena in choosing the way in the
maze. The adult rats also developed behavioural tactics to enter maze arms at 45
degrees or 90 degrees relative to the previously visited arm. The adolescent
rats showed no directional preference and no clear behavioural tactics when
entering maze arms. Based on our findings, we propose that motor lateralization
increases the efficacy of food search and leads to the elaboration of behavioural
tactics. Data obtained may reflect the fact that motor behaviour specialization
develops gradually during ontogenesis and is helpful for adaptation to the
environment.
PMID- 28423994
TI - Seasonal variation in sports participation.
AB - This study explores indicators describing socio-demographics, sports
participation characteristics and motives which are associated with variation in
sports participation across seasons. Data were drawn from the German Socio
Economic Panel which contains detailed information on the sports behaviour of
adults in Germany. Overall, two different measures of seasonal variation are
developed and used as dependent variables in our regression models. The first
variable measures the coefficient of (seasonal) variation in sport-related energy
expenditure per week. The second variable measures whether activity drops below
the threshold as defined by the World Health Organization (WHO). Results suggest
that the organisational setting, the intensity and number of sports practised,
and the motive for participation are strongly correlated with the variation
measures used. For example, both, participation in a sports club and a commercial
facility, are associated with reduced seasonal variation and a significantly
higher probability of participating at a volume above the WHO threshold across
all seasons. These findings give some impetus for policymaking and the planning
of sports programmes as well as future research directions.
PMID- 28423995
TI - Harvesting nutrients from source-separated urine using powdered rice straw.
AB - As a principle of resource-oriented sanitation practice, urine should be
separated from the source and utilized for other purposes such as producing
fertilizer. This is because urine is rich in nutrients; therefore, sending it
directly to wastewater treatment plants causes problems in the regular treatment
process. The addition of solid additives such as powdered rice straw can help
with harvesting nutrients from urine. In this study, the procedure and efficiency
of using powdered rice straw for nutrient harvesting were investigated by
tracking the reductions in ammonia, phosphate, magnesium, and calcium ions, and
the harvested nutrients were identified using crystallography methods. Results
show that the ammonia, phosphate, and magnesium ions showed similar reduction
trends. However, the reduction process was limited by the magnesium and phosphate
availability, which reduced the nutrient harvesting efficiency. The nutrients
harvested with the rice straw were identified to be mostly struvite. Balancing
the phosphate and magnesium ions with ammonia is recommended to improve the
efficiency of nutrient harvesting. The treated powdered rice straw can serve as a
good solid fertilizer, while the remaining urine, which includes fewer nutrients,
can be utilized for irrigation or sent to wastewater treatment plants.
PMID- 28423996
TI - Assessing user acceptance towards automated and conventional sink use for hand
decontamination using the technology acceptance model.
AB - Hand hygiene (HH) prevents harmful contaminants spreading in settings including
domestic, health care and food handling. Strategies to improve HH range from
behavioural techniques through to automated sinks that ensure hand surface
cleaning. This study aimed to assess user experience and acceptance towards a new
automated sink, compared to a normal sink. An adapted version of the technology
acceptance model (TAM) assessed each mode of handwashing. A within-subjects
design enabled N = 46 participants to evaluate both sinks. Perceived Ease of Use
and Satisfaction of Use were significantly lower for the automated sink, compared
to the conventional sink (p < 0.005). Across the remaining TAM factors, there was
no significant difference. Participants suggested design features including jet
strength, water temperature and device affordance may improve HH technology. We
provide recommendations for future HH technology development to contribute a
positive user experience, relevant to technology developers, ergonomists and
those involved in HH across all sectors. Practitioner Summary: The need to
facilitate timely, effective hand hygiene to prevent illness has led to a rise in
automated handwashing systems across different contexts. User acceptance is a key
factor in system uptake. This paper applies the technology acceptance model as a
means to explore and optimise the design of such systems.
PMID- 28423997
TI - Do lipid microemboli induce acute kidney injury during cardiopulmonary bypass?
AB - BACKGROUND: Acute kidney injury (AKI) following cardiopulmonary bypass affects 5%
of patients, representing significant postoperative morbidity and mortality.
Animal models have shown an increased uptake of lipid microemboli (LME) into the
renal vasculature, potentially indicating ischaemic causation. This study tested
a new lipid filtration system (RemoweLL) against a conventional system with no
lipid-depleting capacity to determine the efficacy of the filtration system and
its effects on renal function. METHODS: Thirty consecutive patients underwent
coronary artery bypass graft surgery using either the RemoweLL filtration system
(15 patients) or a conventional cardiopulmonary bypass circuit (15 patients).
Renal function was assessed using cystatin C concentrations as a surrogate marker
of glomerular injury, as well as perioperative glomerular filtration rate (GFR)
and serum creatinine concentrations. Patients were defined as having acute renal
injury if there was an increase in absolute serum creatinine ?3 mg/dL (26.4
umol/L) or 1.5-fold increase from baseline as categorised using the AKIN
criteria. RESULTS: Postoperative differences in LME count between the two groups
were highly significant [p<0.001]. Analysis of peak cystatin C concentrations
showed significantly lower levels in the LME filtration group on the 2nd
postoperative morning [p=0.04]. Two-factor ANOVA revealed a trend towards
interaction, but this failed to reach significance [p=0.06]. There were no
differences throughout the study period in serum creatinine or GFR [p>0.05].
There were no differences in any of the serum or urinary electrolytes.
CONCLUSIONS: This study has shown a trend towards improved cystatin C removal
with LME filtration; with significantly lower peak concentrations, although no
further evidence of renoprotection could be demonstrated. Further research is
warranted to establish possible renal benefits of LME filtration in patients
undergoing cardiac surgery.
PMID- 28423998
TI - Preexisting lesions associated with complete diaphyseal fractures of the third
metacarpal bone in 12 Thoroughbred racehorses.
AB - We characterized features of complete diaphyseal fractures of third metacarpal
bones in Thoroughbred racehorses. Given that stress fractures are known to occur
in the third metacarpal bone, an additional aim was to determine if complete
fractures are associated with signs of a preexisting incomplete stress fracture.
Bilateral metacarpi from 12 Thoroughbred racehorses euthanized because of
complete unilateral metacarpal diaphyseal fracture were examined visually and
radiographically. Open, comminuted, transverse or short oblique fractures
occurred in the middle of the diaphysis or supracondylar region. Periosteal
surface discoloration and bone callus formation contiguous with the fracture line
were present in fractured bones. All contralateral intact metacarpi had gross
anatomic lesions, and 10 had radiographic abnormalities similar to those observed
on fractured metacarpi. Catastrophic metacarpal fractures occurred in racehorses
with bilateral evidence of preexisting bone injury.
PMID- 28423999
TI - Toe brachial index measured by automated device compared to duplex
ultrasonography for detecting peripheral arterial disease in older people.
AB - Introduction To investigate the diagnostic accuracy of an automated toe blood
pressure device for detecting peripheral arterial disease in older people.
Methods Ninety participants underwent toe and brachial blood pressure
measurements and colour duplex ultrasonography of the right lower limb.
Peripheral arterial disease was diagnosed if > 50% arterial obstruction was
identified in any lower limb vessel using colour duplex ultrasonography. A
receiver operating characteristic curve was analysed and the sensitivity and
specificity of commonly used toe brachial index and toe blood pressure values
were determined. Results The optimum toe brachial index threshold value for
diagnosing peripheral arterial disease was 0.72 (sensitivity 76.2%, specificity
75%). The area under the curve was 0.829 (95% CI 0.743 to 0.915, p < 0.0001)
suggesting fair diagnostic accuracy. A toe blood pressure of 70 mmHg was found to
have excellent specificity (97.92%) for detecting PAD but poor sensitivity
(42.86%). Conclusions The accuracy of automated toe blood pressure and TBI
measurements was determined to be good when using colour duplex ultrasound as the
reference standard for the non-invasive diagnosis of peripheral arterial disease.
Results should be interpreted in the context of all clinical signs and symptoms.
PMID- 28424000
TI - Heavy metals and PAHs in canned fish supplies on the Serbian market.
AB - The aim of this study was to determine the level of heavy metals and polycyclic
aromatic hydrocarbons (PAHs) in 57 samples of canned tuna, 25 samples of canned
sardines, and 16 samples of canned smoked sprouts, collected from supermarkets in
Serbia. Heavy metal levels (lead, cadmium, mercury, arsenic, iron, copper, and
zinc) were determined using an inductive coupled plasma mass spectrometry method.
Sixteen analysed PAHs were determined using a gas chromatography-mass
spectrometry method. The trace elements in canned fish were in the range (mg kg
1) of 0.01-0.28 for lead, 0.003-0.08 for cadmium, 0.007-0.64 for mercury, 0.17
3.73 for arsenic, 3.88-52.2 for iron, 0.2-5.95 for copper, and 1.35-44.5 for
zinc. Total PAH levels reached 17.67 ug kg-1 in canned tuna and 15.12 ug kg-1 in
sardines, whereas in smoked sprouts it amounted to 57.19 ug kg-1. Some of the
samples contained cadmium, arsenic, copper, and benzo(a)pyrene above the limits
as set by the European and Serbian legislation.
PMID- 28424001
TI - Corrigendum.
PMID- 28424002
TI - Enzyme-linked immunosorbent assays for coproantigen detection of Ancylostoma
caninum and Toxocara canis in dogs and Toxocara cati in cats.
AB - We report the development and field validation of 2 ELISAs for the detection of
Ancylostoma caninum or Toxocara canis coproantigens in the feces of dogs with
experimental and natural infections, and evidence of cross-reactivity with
respective feline counterparts. A. caninum-specific coproantigens were detected
in feces of experimentally infected dogs starting at 9 d post-infection (dpi),
whereas eggs were not seen until 23 dpi. T. canis-specific coproantigens were
detected in 3 of 5 experimentally infected dogs by 31 dpi, and 4 of the 5 animals
by 38 dpi. T. canis eggs were seen in feces of 4 of the 5 animals by 38 dpi. One
dog had delayed coproantigen detection and low egg output. Additionally, 817
canine and 183 feline fecal samples from naturally infected animals tested by
flotation were subjected to coproantigen ELISA testing. Of these 1,000 canine and
feline samples, 13 and 23 samples, respectively, were positive for "hookworm" or
"roundworm" eggs; 19 and 26 samples were ELISA positive, respectively. The T.
canis ELISA detected T. cati coproantigen in cat fecal samples. Discrepant ELISA
and flotation results were obtained for 16 hookworm- and 13 roundworm-positive
samples. Re-examination of the egg-positive, ELISA-negative samples indicated
several instances of possible misidentification or coprophagy, whereas detection
of antigen in samples without egg observations is likely a reflection of true
infection status with egg shedding below detection levels. There is good
indication, based on accumulated field data, that these antigen tests also detect
other hookworm and ascarid species.
PMID- 28424003
TI - Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by
Mutations in STT3A.
AB - STT3A encodes the catalytic subunit of the oligosaccharyltransferase complex. A
congenital disorder of glycosylation caused by mutations in STT3A has only been
reported in one family to date, associated with a Type I congenital disorder of
glycosylation pattern of transferrin glycoforms. The authors describe a further 5
related individuals with a likely pathogenic variant in STT3A, 2 of whom also had
variants in TUSC3. Common phenotypic features in all symptomatic individuals
include developmental delay, intellectual disability, with absent speech and
seizures. Two individuals also developed episodic hypothermia and altered
consciousness. The family were investigated by autozygosity mapping, which
revealed both a homozygous region containing STT3A and, in addition, a homozygous
deletion of TUSC3 in one child. A likely pathogenic variant in STT3A was
confirmed on Sanger sequencing of all affected individuals: the authors discuss
the molecular findings in detail and further delineate the clinical phenotype of
this rare disorder.
PMID- 28424004
TI - Segmental Diffusion Properties of the Corticospinal Tract and Motor Outcome in
Hemiparetic Children With Perinatal Stroke.
AB - Perinatal stroke injures developing motor systems, resulting in hemiparetic
cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We
used diffusion tensor imaging to assess corticospinal tract diffusion in
hemiparetic children with perinatal stroke. Twenty-eight children (6-18 years)
with unilateral stroke underwent diffusion tensor imaging. Four corticospinal
tract assessments included full tract, partial tract, minitract and region of
interest. Diffusion characteristics (fractional anisotropy, mean, axial, and
radial diffusivity) were calculated. Ratios (lesioned/nonlesioned) were compared
across segments and to validated long-term motor outcomes (Pediatric Stroke
Outcome Measure, Assisting Hand Assessment, Melbourne Assessment). Fractional
anisotropy and radial diffusivity ratios decreased as tract size decreased, while
mean diffusivity showed consistent symmetry. Poor motor outcomes were associated
with lower fractional anisotropy in all segments and radial diffusivity
correlated with both Assisting Hand Assessment and Melbourne Assessment.
Diffusion imaging of segmented corticospinal tracts is feasible in hemiparetic
children with perinatal stroke. Correlations with disability support clinical
relevance and utility in model development for personalized rehabilitation.
PMID- 28424007
TI - Anesthetic-Related Neurotoxicity and Neuroimaging in Children: A Call for
Conversation.
AB - Each year millions of young children undergo procedures requiring sedation or
general anesthesia. An increasing proportion of the anesthetics used are provided
to optimize diagnostic imaging studies such as magnetic resonance imaging.
Concern regarding the neurotoxicity of sedatives and anesthetics has prompted the
US Food and Drug Administration to change labeling of anesthetics and sedative
agents warning against repeated or prolonged exposure in young children. This
review aims to summarize the risk of anesthesia in children with an emphasis on
anesthetic-related neurotoxicity, acknowledge the value of pediatric
neuroimaging, and address this call for conversation.
PMID- 28424008
TI - Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses.
AB - Olfactory axons project from nasal epithelium to the primitive telencephalon
before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ
but arrive via the rostral migratory stream. Synaptic glomeruli and concentric
laminar architecture are unlike other cortices. Fetal olfactory maturation of
neuronal differentiation, synaptogenesis, and myelination remains incomplete at
term and have a protracted course of postnatal development. The olfactory
ventricular recess involutes postnatally but dilates in congenital hydrocephalus.
Olfactory bulb, tract and epithelium are repositories of progenitor stem cells in
fetal and adult life. Diverse malformations of the olfactory bulb can be
diagnosed by clinical examination, imaging, and neuropathologically. Cellular
markers of neuronal differentiation and synaptogenesis demonstrate immaturity of
the olfactory system at birth, previously believed by histology alone to occur
early in fetal life. Immaturity does not preclude function.
PMID- 28424010
TI - Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine
Tasting.
AB - Discrimination of odorous molecules in amniotic fluid occur after 30 weeks'
gestation; fetuses exhibit differential responses to maternal diet. Olfactory
reflexes enable reliable neonatal testing. Olfactory bulbs can be demonstrated
reliably by MRI after 30 weeks' gestation, and their hypoplasia or aplasia also
documented by late prenatal and postnatal MRI. Olfactory axons project from nasal
epithelium to telencephalon before olfactory bulbs form. Fetal olfactory
maturation remains incomplete at term for neuronal differentiation,
synaptogenesis, myelination, and persistence of the transitory fetal ventricular
recess. Immaturity does not signify nonfunction. Olfaction is the only sensory
system without thalamic projection because of its own intrinsic thalamic
equivalent. Diverse malformations of the olfactory bulb can be diagnosed by
clinical examination, imaging, and neuropathology. Some epileptic auras might be
primarily generated in the olfactory bulb. Cranial nerve 1 should be tested in
all neonates and especially in patients with brain malformations,
endocrinopathies, chromosomopathies, and genetic/metabolic diseases.
PMID- 28424011
TI - Endovascular treatment evolution for pure intraorbital arteriovenous fistula:
Three case reports and literature review.
AB - Background and importance Intraorbital arteriovenous fistulas (IOAVFs) are rare
and cause eye redness, exophthalmos, blurry vision and bruit. Whereas in the past
they were treated conservatively, surgically or transarterially, recent
developments in transvenous embolization have improved their treatment. In this
paper the authors report three cases of IOAVFs treated endovascularly and review
the evolution of treatment options. Methods Three cases of purely IOAVF enrolled
in our center were reported and a PubMed literature search was performed using
"pure intraorbital arteriovenous fistula" and "arteriovenous fistula of the optic
nerve sheath." A total of 21 papers were reviewed in full, focusing primarily on
the treatment and outcomes. Results A total of 26 patients were obtained,
including our three patients and 23 patients reported in the literature. In nine
patients treated conservatively, four spontaneous occlusions, one visual
deterioration and four cases with unknown outcome were reported. In another 18
patients, 29 therapies (including five surgical treatment, 11 transarterial
embolizations and 13 transvenous embolizations) were attempted and resulted in 12
cures, five visual deteriorations and one without reported outcome. More
recently, transvenous embolization has become the mainstay of IOAVF treatment. Of
the 21 patients assessed between 2000 and 2013, a transvenous approach was
attempted in 13 patients; nine patients were cured without any adverse events.
Conclusion Development and improvement of transvenous techniques are found to be
safe and effective for patients with IOAVF.
PMID- 28424012
TI - Internal carotid artery agenesis: A case report and review of literature.
AB - Congenital agenesis of the internal carotid artery is a very rare anomaly.
Intracranial circulation in the involved internal carotid artery territory is
maintained by collateral circulation from the contralateral internal carotid
artery through the anterior communicating artery and from the vertebrobasilar
system through the posterior communicating artery. Usually, patients with
internal carotid artery agenesis are asymptomatic due to collateral circulation,
but they may present with headache, seizures, or transient ischemic attack.
Aneurysms have also been reported to be associated with this entity. Computed
tomography angiography, magnetic resonance angiography, and digital subtraction
angiography are commonly used modalities to make the diagnosis. Unenhanced skull
base computed tomography will show the absence of carotid canal, thus
differentiating from carotid hypoplasia. We report on a case of right internal
carotid artery agenesis with discussion of embryogenesis, clinical presentation,
and imaging findings.
PMID- 28424013
TI - Anterior spinal artery aneurysm in aortic stenosis of different etiology: Report
of three cases.
AB - Isolated aneurysms of spinal arteries are rare. Spinal artery aneurysms are
commonly found in association with spinal cord arteriovenous malformation and
coarctation of aorta and rarely with aortic arch interruption and Klippel
Trenaunay syndrome. Spinal angiograms are the gold standard for diagnosing these
spinal artery aneurysms but with the advances in computed tomography technology
these aneurysms can also be very well demonstrated in computed tomography
angiograms. We describe three cases of anterior spinal artery aneurysm, those are
flow related aneurysms, associated with coarctation of aorta and with Takayasu
arteritis.
PMID- 28424014
TI - Semi-quantitative analysis of cerebral FDG-PET reveals striatal hypermetabolism
and normal cortical metabolism in a case of VGKCC limbic encephalitis.
AB - In the context of delayed autoimmune encephalitis antibody results, functional
imaging can support the diagnosis of limbic encephalitis associated with anti
voltage-gated potassium channel complex (VGKCC) antibodies. Here we present a
typical case of VGKCC encephalitis in a 69-year-old woman whose symptoms
responded to plasmapheresis. A cerebral 18F-fluoro-2-deoxy-d-glucose positron
emission tomography (FDG-PET) scan performed prior to commencing treatment
revealed striatal hypermetabolism assessed qualitatively and semi-quantitatively,
with normal uptake in the cortex and cerebellum when analysed semi
quantitatively. Repeat FDG-PET imaging performed three months later revealed
normalisation of striatal hypermetabolism. Previous case reports have described
striatal hypermetabolism and/or cortical hypometabolism in patients with VGKCC
encephalitis. However, most of these descriptions were based on qualitative
analyses only and may represent the relative change in cortical metabolism
compared with striatal metabolism. We recommend semi-quantitative analysis of
cerebral FDG-PET, in addition to reporting the qualitative FDG-PET images.
PMID- 28424015
TI - Susceptibility weighted imaging in acute cerebral ischemia: review of emerging
technical concepts and clinical applications.
AB - Susceptibility weighted imaging (SWI) is an essential magnetic resonance imaging
sequence in the assessment of acute ischemic stroke. In this article, we discuss
the physics principals and clinical application of conventional SWI and multi
echo SWI sequences. We review the research evidence and practical approach of SWI
in acute ischemic stroke by focusing on the detection and characterization of
thromboembolism in the cerebral circulation. In addition, we discuss the role of
SWI in the assessment of neuroparenchyma by depiction of asymmetric hypointense
cortical veins in the ischemic territory (surrogate tissue perfusion), detection
of existing microbleeds before stroke treatment and monitoring for hemorrhagic
transformation post-treatment. In conclusion, the SWI sequence complements other
parameters in the stroke magnetic resonance imaging protocol and understanding of
the research evidence is vital for practising stroke neurologists and
neuroradiologists.
PMID- 28424016
TI - Acute brain injury following illicit drug abuse in adolescent and young adult
patients: spectrum of neuroimaging findings.
AB - The use of illicit drugs is currently a major medical problem among adolescents.
Several illicit drugs have a high abuse potential and can be neurotoxic causing
high morbidity and mortality. The clinical manifestation of adolescents with
acute drug-induced neurotoxicity is often characterized by non-specific symptoms
and findings. Early diagnosis is important to prevent death and permanent long
term neurological impairments. We report on clinical and neuroimaging findings in
five adolescents with acute brain imaging following illicit drug intoxication to
highlight the role of neuroimaging findings in the diagnostic work-up of
pediatric acute drug-induced neurotoxicity. Our patients reveal two main
neuroimaging patterns of brain injury: diffuse symmetric subcortical white matter
injury with preferential cerebellar involvement (leukoencephalopathy pattern) or
multiple foci of ischemic infarctions in a non-arterial territory distribution
(ischemic pattern). Familiarity with these two neuroimaging patterns of findings
in the evaluation of magnetic resonance imaging studies in adolescents with
acutely altered mental status may suggest the correct diagnosis, narrow the
differential diagnosis, and consequently allow early initiation of targeted
laboratory investigations and treatment, potentially improving outcome.
PMID- 28424017
TI - Computed tomography perfusion-based selection of endovascularly treated acute
ischaemic stroke patients - Are there lessons to be learned from the pre-evidence
era?
AB - Introduction Some of the latest groundbreaking trials suggest that noncontrast
cranial computed tomography and computed tomography-angiography are sufficient
tools for patient selection within six hours of symptom onset. Before
endovascular stroke therapy became the standard of care, patient selection was
one of the most useful tools to avoid futile reperfusions. We report the outcomes
of endovascularly treated stroke patients selected with a perfusion-based
paradigm and discuss the implications in the current era of endovascular
treatment. Material and methods After an interdisciplinary meeting in September
2012 we agreed to select thrombectomy candidates primarily based on computed
tomography perfusion with a cerebral blood volume Alberta Stroke Program Early
Computed Tomography Scale (CBV-ASPECTS) of <7 being a strong indicator of futile
reperfusion. In this study, we retrospectively screened all patients with an M1
thrombosis in our neurointerventional database between September 2012 and
December 2014. Results In 39 patients with a mean age of 69 years and a median
admission National Institute of Health Stroke Scale of 17 the successful
reperfusion rate was 74% and the favourable outcome rate at 90 days was 56%.
Compared to previously published data from our database 2007-2011, we found that
a two-point increase in median CBV-ASPECTS was associated with a significant
increase in favourable outcomes. Conclusion Computed tomography perfusion imaging
as an additional selection criterion significantly increased the rate of
favourable clinical outcome in patients treated with mechanical thrombectomy.
Although computed tomography perfusion has lost impact within the six-hour
period, we still use it in cases beyond six hours as a means to broaden the
therapeutic window.
PMID- 28424018
TI - Correction to: Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI)
in rats: identification of urinary metabolites.
PMID- 28424019
TI - Primary trauma care: a 20-year review.
AB - This year marks the 20th anniversary of the Primary Trauma Care Foundation (PTC),
which provides a course aimed at providing a systematic approach to trauma and
the unwell patient in low- and middle-income countries. The course is based on
the original 36-page PTC manual and a key ethos of being appropriate to the
target audience, affordable to those who need it, adaptable to the needs of each
local area and sustainable to perpetuate itself. The concept is simple: a two-day
course for candidates, followed by a one-day instructor course, and finally a
first course delivered to local healthcare staff by the first cohort. Now in its
20th year, its reach spans 76 countries, is ingrained in the syllabus of many
healthcare systems and continues to reach new territories with a programme shown
to produce a measurable improvement in the care delivered.
PMID- 28424020
TI - The utility of an obesity-specific small for gestational age standard for
pregnancies complicated by maternal obesity.
AB - INTRODUCTION: An obesity-specific standard for small for gestational age (SGA)
pregnancies may help identify additional at risk pregnancies. METHODS: This was a
retrospective cohort study of all non-anomalous singleton neonates born in Texas
from 2006-2011. Analysis was limited to births between 34 and 42 weeks gestation.
Two SGA birth weight standards (birth weight <=10th centile) were generated, one
using the entire population (SGApop) and another using obese pregnancies
(SGAcust). The outcomes of interest included: risks of stillbirth, neonatal
death, 5-minute Apgar score below 7, NICU admission, and assisted ventilation >6
h. RESULTS: Using the population standard, the prevalence of SGA complicated by
obesity was 8.1%, compared with 10.3% using the obesity-specific standard. 10,457
additional pregnancies were identified as SGA. Compared to obese AGA pregnancies,
the aHR for stillbirth was 5.45 [4.28, 6.94] for SGApop, and 1.21 [0.54, 2.74]
for SGAcust-pop. The risks for the following neonatal complications were slightly
higher for SGAcust-pop group compared to AGA group: neonatal death aOR 1.40
[1.05, 1.87], low 5-minute Apgar 1.31 [1.09, 1.57], and NICU admission 1.13
[1.03, 1.25]. These risks were lower than SGApop. CONCLUSIONS: Using an obesity
specific SGA standard, a subgroup of pregnancies with marginally increased risk
for neonatal complications was identified.
PMID- 28424021
TI - Air in intravenous lines: a need to review old opinions.
PMID- 28424022
TI - Analytical validation of an automated assay for ferric-reducing ability of plasma
in dog serum.
AB - We performed analytical validation of an automated ferric-reducing ability of
plasma (FRAP) assay in the serum of dogs. Intra- and interassay precision,
accuracy, detection limit, and effects of hemolysis and lipemia were evaluated.
Intra- and interassay coefficients of variation were <1% and <13%, respectively.
The assay showed a high correlation with a FRAP assay described previously, and
results were linear when serial sample dilutions were tested. The detection limit
was lower than the values observed in sera from healthy dogs; decreased serum
FRAP was found in dogs with leishmaniosis. Lipemia and hemolysis caused a
significant increase in the results of the assay.
PMID- 28424023
TI - Erratum.
PMID- 28424024
TI - Molecular profiling and bioactive potential of an endophytic fungus Aspergillus
sulphureus isolated from Sida acuta: a medicinal plant.
AB - CONTEXT: Sida acuta Burm.f. (Malvaceae) extracts are reported to have
applications against malaria, diuretic, antipyretic, nervous and urinary
diseases. No fungal endophytes of S. acuta are reported. OBJECTIVE: Isolation,
identification and evaluation of antibacterial, antioxidant, anticancer and
haemolytic potential of fungal endophytes from the ethnomedcinal plant S. acuta.
MATERIALS AND METHODS: Sida acuta stem segments were placed on PDA medium to
isolate endophytic fungi. The fungus was identified by genomic DNA analysis and
phylogenetic tree was constructed using ITS sequences (GenBank) to confirm
species. The antibacterial efficacy of Aspergillus sulphureus MME12 ethyl acetate
extract was tested against Gram-positive and Gram-negative pathogenic bacteria.
DPPH free radical scavenging activity, anticancer and DNA fragmentation against
EAC cells, and direct haemolytic activity (100-500 MUg/mL) using human
erythrocytes were determined. RESULTS AND DISCUSSION: The ethyl acetate extract
of A. sulphureus (Fresen.) Wehmer (Trichocomaceae) demonstrated significant
antibacterial potential against Staphylococcus aureus, Bacillus subtilis,
Escherichia coli and Salmonella typhi compared to streptomycin. MIC against test
pathogens was in the range of 15.6-62.5 MUg/mL. The antioxidant results revealed
significant RSA from 12.43% to 62.02% (IC50 = 350.4 MUg/mL, p <= 0.05). MME12
offered considerable inhibition of EAC proliferation (23% to 84%, IC50 = 216.7
MUg/mL, p <= 0.05) supported by DNA fragmentation studies. The extract also
offered insignificant haemolysis (5.6%) compared to Triton X-100. CONCLUSIONS: A
single endophytic fungus, A. sulphureus MME12 was isolated and identified using
molecular profiling. The above-mentioned findings support the pharmacological
application of A. sulphureus MME12 extract and demand for purification of the
active principle(s).
PMID- 28424025
TI - Selective reminding of prospective memory in Multiple Sclerosis.
AB - OBJECTIVE: Multiple sclerosis (MS) is associated with prospective memory (PM)
deficits, which may increase the risk of poor functional/health outcomes such as
medication non-adherence. This study examined the potential benefits of selective
reminding to enhance PM functioning in persons with MS. METHOD: Twenty-one
participants with MS and 22 healthy adults (HA) underwent a neuropsychological
battery including a Selective Reminding PM (SRPM) experimental procedure.
Participants were randomly assigned to either: (1) a selective reminding
condition in which participants learn (to criterion) eight prospective memory
tasks in a Selective Reminding format; or (2) a single trial encoding condition
(1T). RESULTS: A significant interaction was demonstrated, with MS participants
receiving greater benefit than HAs from the SR procedure in terms of PM
performance. Across diagnostic groups, participants in the SR conditions (vs. 1T
conditions) demonstrated significantly better PM performance. Individuals with MS
were impaired relative to HAs in the 1T condition, but performance was
statistically comparable in the SR condition. CONCLUSIONS: This preliminary study
suggests that selective reminding can be used to enhance PM cue detection and
retrieval in MS. The extent to which selective reminding of PM is effective in
naturalistic settings and for health-related behaviours in MS remains to be
determined.
PMID- 28424026
TI - Walking ability following Hybrid Assistive Limb treatment for a patient with
chronic myelopathy after surgery for cervical ossification of the posterior
longitudinal ligament.
AB - CONTEXT: The hybrid assistive limb (HAL) (the wearable robot) can assist kinesis
during voluntary control of hip and knee joint motion by detecting the wearer's
bioelectric signals on the surface of their skin. The purpose of this study was
to report on walking ability following the wearable robot treatment in a patient
with chronic myelopathy after surgery for cervical ossification of the posterior
longitudinal ligament (OPLL). FINDINGS: The patient was a 66-year-old woman with
cervical OPLL who was able to ambulate independently with the aid of bilateral
crutches. The wearable robot treatment was received once every 2 weeks for ten
sessions beginning approximately 14 years after surgery. Improvements were
observed in gait speed (BL 22.5; post 46.7 m/min), step length (BL 0.36; post
0.57 m), and cadence (BL 61.9; post 81.6 m/min) based on a 10-m walk test and a 2
minute walk test (BL 63.4; post 103.7 m) assessing total walking distance. The
improvements in walking ability were maintained after the wearable robot
treatment for 6 months. CONCLUSION: We report the functional recovery in the
walking ability of a patient with chronic cervical myelopathy following the
wearable robot treatment, suggesting that as a rehabilitation tool, the wearable
robot has the potential to effectively improve functional ambulation in chronic
cervical myelopathy patients whose walking ability has plateaued, even many years
after surgery.
PMID- 28424027
TI - The value of European exchange programs for early career family doctors.
AB - The Hippokrates Exchange programme (HEP) is designed to give early career General
Practitioners (Associates in Training (AITs)/First5s) first-hand experience into
concepts of a primary healthcare system outside of their host country. The aim is
to improve GP knowledge and skills, inspire professional development and promote
a global approach to primary care. Although an increasing number are taking up
this opportunity, their views and experiences of international exchanges are not
well described. The aim of the study was to explore the experiences of
AITs/First5s following their HEP exchanges. This qualitative study analysed 16
post-exchange reports of UK participants visiting 10 European countries via the
HEP, using a thematic approach. Participants were unanimously positive about
their exchange experiences. The themes that emerged were (1) Comparison of
primary care practice (2) Infrastructure of host primary care (3) Motivation and
experience of exchanges and (4) Learning and reflection. Participants displayed
considerable benefits from these exchanges by broadening their experience in
different primary care systems and identifying improvements to be incorporated
into their UK practice.
PMID- 28424028
TI - Church-Based Recruitment to Reach Korean Immigrants: An Integrative Review.
AB - Although the Korean church has been frequently used to recruit Korean immigrants
in research, little is known about the specific strategies and process. The
purpose of this integrative review was to describe recruitment strategies in
studies of Korean immigrants and to identify the process of Korean church-based
recruitment. Thirty-three studies met inclusion criteria. Four stages of church
based recruitment were identified: initiation, endorsement, advertisement, and
implementation. This review identified aspects of the church-based recruitment
process in Korean immigrants, which are different from the Black and Hispanic
literature, due to their hierarchical culture and language barriers. Getting
permission from pastors and announcing the study by pastors at Sunday services
were identified as the key components of the process. Using the church newsletter
to advertise the study was the most effective strategy for the advertisement
stage. Despite several limitations, church-based recruitment is a very feasible
and effective way to recruit Korean immigrants.
PMID- 28424029
TI - Baseline executive control ability and its relationship to language therapy
improvements in post-stroke aphasia: a systematic review.
AB - PURPOSE: To review current evidence on the relationship between executive control
(EC) and post-treatment language gains in adults with post-stroke aphasia.
METHOD: Electronic databases (CINAHL, Cochrane Trials, Embase, MEDLINE, MEDLINE
in-Process and PsycINFO) were systematically searched (year 2000 - present).
Abstracts and full-text articles were reviewed by two independent raters against
pre-specified criteria: original research with N > 2; at least 90% adults with
stroke, all undergoing treatment for acquired aphasia; pre-treatment EC abilities
were compared to language gains post-treatment across studies. Critical appraisal
was conducted using the Cochrane group and Single-Case Experimental Design (SCED)
methods. Data were extracted and summarised descriptively. RESULTS: Search
results yielded 2272 unique citations; ultimately 15 studies were accepted for
review. Both pre-treatment EC and language abilities appear to be important
indicators of treatment success, especially in moderate-severe aphasia. This
relationship emerged when EC was measured using specific (e.g., divided
attention), as opposed to broad (e.g., reasoning) tasks, and primarily when
naming therapy was administered; intensive constraint-induced therapy did not
correlate with treatment success. CONCLUSIONS: EC is a promising prognostic
variable regarding language recovery, but further research is required using a
priori declared theoretical EC models, along with properly powered samples,
standardised EC tasks and treatment protocols.
PMID- 28424030
TI - Expanded dengue syndrome: three concomitant uncommon presentations in the same
patient.
AB - We report a case of expanded dengue syndrome, where three uncommon presentations
occurred concomitantly. A patient with dengue haemorrhagic fever presented
initially with acute acalculous cholecystitis along with acute pancreatitis, but
later on, during resolution of pancreatitis and cholecystitis, developed
pancytopenia, most likely due to haemophagocytic syndrome. Such presentations,
besides being rare themselves, have not been reported to occur concomitantly, in
the same patient, during the same disease process.
PMID- 28424032
TI - The onslaught of infectious disease.
PMID- 28424031
TI - Yellow fever from Angola and Congo: a storm gathers.
AB - In common with Zika, Chikungunya and Dengue, Yellow Fever (YF) is an arthropod
borne flavivirus. It is transmitted between humans and from monkeys by mosquitoes
of the Aedes aegypti (its principal vector), haemogogus and albopictus varieties.
Three cycles of transmission may occur: urban; sylvatic; and intermediate.
Recently, sub-Saharan Africa has seen the resurgence of this neglected disease.
The current YF outbreak in Angola began in December 2015 in the capital Luanda
and by October 2016 there had been > 4300 suspected cases, with 376 deaths (case
fatality rate = 8.8%). A total of 884 were laboratory confirmed but it is likely
that case numbers may be seriously underestimated. YF has subsequently quickly
spread to neighbouring Congo and further afield to Kenya and also China, this
being of grave concern as this was a first introduction of YF to Asia. YF has
recently hit Brazil, with 555 suspected cases and 107 deaths reported by the end
of January 2017. Extremely rapid unplanned urban migration in Africa by non
immune rural populations to already densely populated cities, where high
densities of mosquitoes co-exist with city dwellers in makeshift flimsy
accommodation, poses a ready recipe for an epidemic of massive proportion. In
such conditions, with enormously strained public services existing among the most
needy and vulnerable populations, mosquito control programmes are nearly
impossible. YF in Congo is a tempest barely restrained. However, it is one that
can be controlled by focused and committed international collaboration, by
intense and united political will and by the marriage of old and trusted
techniques: a vaccine almost a century old and some of the most modern
technologies available to man.
PMID- 28424033
TI - A MELAS phenotype is not necessarily MELAS.
PMID- 28424034
TI - Clinical and laboratory factors associated with mortality in dengue.
AB - Dengue is endemic in more than 100 countries, giving rise to an increased number
of deaths in the last five years in the South-East Asian region. We report our
findings from a retrospective study of adults admitted with confirmed dengue at
our institution. We studied the clinical and laboratory parameters associated
with mortality in these patients. Of the 172 hospitalised patients studied, 156
(90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered
sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum
creatinine, higher serum transaminase and lower serum albumin levels to be
significantly associated with mortality in dengue. Further, using stepwise
multivariate logistic regression, altered sensorium ( P = 0.006) and
hypoalbuminemia ( P = 0.013) were identified as independent predictors of
mortality in dengue. Identification of these parameters early in the course of
disease should prompt intensification of treatment in dengue cases.
PMID- 28424035
TI - Coexistence of tuberculosis and malignancy: a mere coincidence or a causal
association.
AB - Tuberculosis (TB) and malignancy are among the most important current global
health problems. Many authors suggest that their coexistence is a chance
association owing to their high prevalence. There is, however, enough evidence
that one condition may predispose the other. In our retrospective report of two
cases, TB in draining lymph nodes was discovered incidentally on histopathology,
following surgical resection for malignancy. The possibility of coexistent
lesions, especially in regions endemic for TB, mandate a detailed
histopathological examination to prevent the chances of diagnostic failure and
thus therapeutic error.
PMID- 28424037
TI - Aortic Customized Stent-Graft Treatment of Postnephrectomy Renal Pedicle
Arteriovenous Fistula.
AB - A postnephrectomy renal acquired arteriovenous fistula (AVF) is a rare clinical
entity that may cause high-output heart failure. Most of the cases are identified
time along after surgery. We present a case of a postnephrectomy renal AVF
treated with aortic customized stent-graft.
PMID- 28424038
TI - A Novel Method for the Treatment of Bilateral Hypogastric Aneurysms Using Hybrid
Polytetrafluoroethylene Graft.
AB - Open aortic aneurysm repair in the setting of bilateral hypogastric aneurysms is
technically challenging. We present a novel technique for open surgical repair
for bilateral hypogastric aneurysms using the Gore hybrid vascular graft (GVHG;
W. L. Gore and Associates Inc, Flagstaff, Arizona). The GVHG is an expanded
polytetrafluoroethylene graft with a nitinol stent at 1 end designed for
hemodialysis access. The GVHG has been also been used for aortic debranching and
treatment of occlusive disease. We describe the first report using GVHG to repair
hypogastric aneurysms.
PMID- 28424039
TI - Endovascular Treatment of Ischemic Stroke: An Updated Meta-Analysis of Efficacy
and Safety.
AB - BACKGROUND: Recent randomized trials demonstrated the superiority of the
mechanical thrombectomy over the best medical treatment in patients with acute
ischemic stroke due to an occlusion of arteries of proximal anterior circulation.
In this updated meta-analysis, we aimed to summarize the total clinical effects
of the treatment, including the last trials. METHODS: We performed literature
search of Randomized Crontrolled Trials (RCTs) published between 2010 and October
2016, comparing endovenous thrombolysis plus mechanical thrombectomy
(intervention group) with best medical care alone (control group). We identified
8 trials. Primary outcomes were reduced disability at 90 days from the event and
symptomatic intracranial hemorrhage. Statistical analysis was performed pooling
data into the 2 groups, evaluating outcome heterogeneity. The Mantel-Haenszel
method was used to calculate odds ratios (ORs). RESULTS: We analyzed data for
1845 patients (interventional group: 911; control group: 934). Mechanical
thrombectomy contributed to a significant reduction in disability rate compared
to the best medical treatment alone (OR: 2.087; 95% confidence interval [CI]:
1.718-2.535; P < .001). We calculated that for every 100 treated patients, 16
more participants have a good outcome as a result of mechanical treatment. No
significant differences between groups were observed concerning the occurrence of
symptomatic hemorrhage (OR: 1.021; 95% CI: 0.641-1.629; P = .739). CONCLUSION:
Mechanical thrombectomy contributes to significantly increase the functional
benefit of endovenous thrombolysis in patients with acute ischemic stroke caused
by arterial occlusion of proximal anterior circulation, without reduction in
safety. These findings are relevant for the optimization of the acute stroke
management, including the implementation of networks between stroke centers.
PMID- 28424040
TI - Challenges of Takayasu Arteritis in Pregnancy: A Case Report.
AB - Takayasu arteritis is a rare, chronic vasculitis of unknown etiology
characterized by inflammation of the aorta and its main branches. Although
Takayasu arteritis mostly affects women of childbearing age, there is a paucity
in the literature on pregnancy associated with Takayasu arteritis. Pregnant
patients are at increased risk of cardiovascular complications, including
hypertension and congestive heart failure, which may jeopardize both maternal and
fetal outcomes. Furthermore, optimal management has not yet been established for
pregnant patients with Takayasu arteritis, posing a clinical challenge. We
present a case of a young woman with Takayasu arteritis whose symptoms and
disease activity improved during 2 pregnancies. Although her first pregnancy was
complicated with preeclampsia, gestational diabetes, and preterm vaginal
delivery, her second pregnancy was uneventful. This case provides a rare glimpse
of Takayasu arteritis in pregnancy and highlights the challenges of medical
management in gravid patients.
PMID- 28424041
TI - Endovascular Treatment of Massive Axillary Artery Aneurysm for Palliation.
AB - Atherosclerotic axillary artery aneurysms are rare. We report a case of a ninety
six year old female who presented with a pulsatile left breast mass causing her
intractable pain. She was diagnosed with a massive axillary artery aneurysm which
was treated with and endovascular aneurysm repair for palliation of her symptoms.
PMID- 28424042
TI - The Effect of a New Angiographic Imaging Technology on Radiation Dose in Visceral
Embolization Procedures.
AB - PURPOSE: To evaluate the impact of a new angiographic imaging technology on
radiation dose during visceral embolization procedures involving both fluoroscopy
and digital subtraction angiography. MATERIAL AND METHODS: A retrospective
analysis from a single-center consecutive series of patients was performed
comparing 2 angiographic imaging systems. The AlluraClarity (CIQ; Philips
Healthcare, Best, the Netherlands) was used in 100 patients (n = 59 male, mean
age: 70.6 years) from July 2013 to April 2014 and compared to the former
AlluraXper (AX) technology used in 139 patients (n = 71 male, mean age: 70.1
years) from May 2011 to June 2013. Patients were categorized according to body
mass index (BMI [kg/m2])-group 1: BMI <25, group 2: BMI >=25 and <30, and group
3: BMI >=30. Fluoroscopy time, the total dose of iodinated contrast administered,
and procedural AirKerma (Ka, r [mGy]) were obtained. RESULTS: Mean BMI was 26.4
+/- 5.0 kg/m2 in the CIQ and 26.4 +/- 7.1 kg/m2 in the AX group ( P = .93).
Fluoroscopy time and the amount of contrast media were equally distributed. Ka, r
was 1342.9 mGy versus 2214.8 mGy ( P < .001, t test) when comparing CIQ to AX.
Comparing CIQ to AX, BMI subgroup analysis revealed a mean Ka, r of 970.1 to
1586.1 mGy ( P = .003, t test), 1484.7 to 2170.1 mGy ( P = .02, t test), and
1848.8 to 3348.9 mGy ( P = .001, t test) in BMI groups 1, 2, and 3, respectively.
CONCLUSION: The CIQ technology significantly reduced mean radiation dose by 39.4%
for visceral embolization procedures when compared to fluoroscopy time and
contrast media dose. This dose relationship was consistent across all BMI groups.
PMID- 28424043
TI - Nutcracker Syndrome: Case Report on the Management of Recurrent Stenosis After
Stenting.
AB - Nutcracker syndrome is a clinical entity leading to renal venous hypertension due
to extrinsic compression of the left renal vein by the superior mesenteric
artery. Current surgical therapy involves placement of an oversized renal vein
stent with partial protrusion into the inferior vena cava (IVC) to relieve
stenosis and prevent stent migration. Here, we present a patient with intractable
pain and hematuria secondary to nutcracker syndrome who underwent left renal vein
stent placement and developed recurrent symptoms due to flow-limiting kinking at
the left renal hilum, with partial obstruction of the IVC from pseudointimal
hyperplasia. This was treated with stent excision and construction of a left
neorenal vein bypass. Thus, given these complications, we should perhaps revisit
the recommendations for oversizing of the stent.
PMID- 28424044
TI - Emergent Carotid Thromboendarterectomy for Acute Symptomatic Occlusion of the
Extracranial Internal Carotid Artery.
AB - BACKGROUND: Strokes secondary to acute internal carotid artery (ICA) occlusion
are associated with an extremely poor prognosis. The best treatment approach in
this setting is still unknown. The aim of our study was to evaluate the efficacy,
safety, and outcomes of emergent surgical revascularization of acute extracranial
ICA occlusion in patients with minor to severe ischemic stroke. METHODS: A
retrospective analysis was performed using prospectively collected data of
consecutive patients who underwent carotid thromboendarterectomy for symptomatic
acute ICA occlusion during the period from January 2013 to December 2015. Primary
outcomes were disability at 90 days assessed by the modified Rankin Scale (mRS)
and neurological deficit at discharge assessed using the National Institute of
Health Stroke Scale (NIHSS). Secondary outcomes were the recanalization rate, 30
day overall mortality, and any intracerebral bleeding. RESULTS: During the study
period, a total of 6 patients (5 men and 1 woman) with a median age of 64 years
(range: 58-84 years) underwent emergent reconstruction for acute symptomatic ICA
occlusion within a median of 5.4 hours (range: 2.9-12.0 hours) after symptoms
onset. The median presenting NIHSS score was 10.5 points (range: 4-21). Before
surgery, 4 patients (66.7%) had been treated by systemic recombinant tissue
plasminogen activator lysis. The median time interval between initiation of
intravenous thrombolysis and carotid thromboendarterectomy was 117.5 minutes
(range: 65-140 minutes). Patency of the ICA was achieved in all patients. On
discharge, the median NIHSS score was 2 points (range: 0-11 points). There was no
postoperative intracerebral hemorrhage and zero 30-day mortality rate. At 3
months, 5 patients (83.3%) had a good clinical outcome (mRS <= 2). CONCLUSION:
Patients presenting with minor to severe ischemic stroke syndromes due to
isolated extracranial ICA occlusion may benefit from emergent carotid
revascularization. Thorough preoperative neuroimaging is essential to aid in
selecting eligible candidates for acute surgical intervention.
PMID- 28424045
TI - A modified Mediterranean dietary intervention for adults with major depression:
Dietary protocol and feasibility data from the SMILES trial.
AB - BACKGROUND: The SMILES trial was the first randomized controlled trial (RCT)
explicitly designed to evaluate a dietary intervention, conducted by qualified
dietitians, for reducing depressive symptomatology in adults with clinical
depression. OBJECTIVES: Here we detail the development of the prescribed diet
(modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive
disorders (MDDs) that was designed specifically for the SMILES trial. We also
present data demonstrating the extent to which this intervention achieved
improvements in diet quality. METHODS: The ModiMedDiet was designed using a
combination of existing dietary guidelines and scientific evidence from the
emerging field of nutritional psychiatric epidemiology. Sixty-seven community
dwelling individuals (Melbourne, Australia) aged 18 years or over, with current
poor quality diets, and MDDs were enrolled into the SMILES trial. A retention
rate of 93.9 and 73.5% was observed for the dietary intervention and social
support control group, respectively. The dietary intervention (ModiMedDiet)
consisted of seven individual nutrition counselling sessions delivered by a
qualified dietitian. The control condition comprised a social support protocol
matched to the same visit schedule and length. RESULTS: This manuscript details
the first prescriptive individualized dietary intervention delivered by
dietitians for adults with major depression. Significant improvements in dietary
quality were observed among individuals randomized to the ModiMedDiet group.
These dietary improvements were also found to be associated with changes in
depressive symptoms. DISCUSSION/CONCLUSION: The ModiMedDiet, a novel and
individually tailored intervention designed specifically for adults with major
depression, can be effectively implemented in clinical practice to manage this
highly prevalent and debilitating condition. TRIAL REGISTRATION: Australia and
New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29
February 2012.
PMID- 28424046
TI - Perspectives of policy-makers and stakeholders about health care waste management
in community-based care in South Africa: a qualitative study.
AB - BACKGROUND: In South Africa, a new primary health care (PHC) re-engineering
initiative aims to scale up the provision of community-based care (CBC). A
central element in this initiative is the use of outreach teams comprising nurses
and community health workers to provide care to the largely poor and marginalised
communities across the country. The provision of care will inevitably lead to an
increase in the amount of health care waste (HCW) generated in homes and suggests
the need to pay more attention to the HCW that emanates from homes where there is
care of a patient. CBC in South Africa is guided by the home-based care policy.
However, this policy does not deal with issues about how HCW should be managed in
CBC. This study sought to explore health care waste management (HCWM) in CBC in
South Africa from the policy-makers' and stakeholders' perspective. METHODS: Semi
structured interviews were conducted with 9 policy-makers and 21 stakeholders
working in 29 communities in Durban, South Africa. Interviews were conducted in
English; were guided by an interview guide with open-ended questions. Data was
analysed thematically. RESULTS: The Durban Solid waste (DSW) unit of the
eThekwini municipality is responsible for overseeing all waste management
programmes in communities. Lack of segregation of waste and illegal dumping of
waste were the main barriers to proper management practices of HCW at household
level while at the municipal level, corrupt tender processes and inadequate
funding for waste management programmes were identified as the main barriers. In
order to address these issues, all the policy-makers and stakeholders have taken
steps to collaborate and develop education awareness programmes. They also liaise
with various government offices to provide resources aimed at waste management
programmes. CONCLUSIONS: HCW is generated in CBC and it is poorly managed and
treated as domestic waste. With the rollout of the new primary health care model,
there is a greater need to consider HCWM in CBC. There is need for the Department
of Health to work together with the municipality to ensure that they devise
measures that will help to deal with improper HCWM in the communities.
PMID- 28424047
TI - Deciphering mechanisms underlying the genetic variation of general production and
liver quality traits in the overfed mule duck by pQTL analyses.
AB - BACKGROUND: The aim of this study was to analyse the mechanisms that underlie
phenotypic quantitative trait loci (QTL) in overfed mule ducks by identifying co
localized proteomic QTL (pQTL). The QTL design consisted of three families of
common ducks that were progeny-tested by using 294 male mule ducks. This
population of common ducks was genotyped using a genetic map that included 334
genetic markers located across 28 APL chromosomes (APL for Anas platyrhynchos).
Mule ducks were phenotyped for 49 traits related to growth, metabolism,
overfeeding ability and meat and fatty liver quality, and 326 soluble fatty liver
proteins were quantified. RESULTS: One hundred and seventy-six pQTL and 80
phenotypic QTL were detected at the 5% chromosome-wide significance threshold.
The great majority of the identified pQTL were trans-acting and localized on a
chromosome other than that carrying the coding gene. The most significant pQTL
(1% genome-wide significance) were found for alpha-enolase on APL18 and fatty
acid synthase on APL24. Some proteins were associated with numerous pQTL (for
example, 17 and 14 pQTL were detected for alpha-enolase and apolipoprotein A1,
respectively) and pQTL hotspots were observed on some chromosomes (APL18, 24, 25
and 29). We detected 66 co-localized phenotypic QTL and pQTL for which the
significance of the two-trait QTL (2t-QTL) analysis was higher than that of the
strongest QTL using a single-trait approach. Among these, 16 2t-QTL were
pleiotropic. For example, on APL15, melting rate and abundance of two alpha
enolase spots appeared to be impacted by a single locus that is involved in the
glycolytic process. On APLZ, we identified a pleiotropic QTL that modified both
the blood level of glucose at the beginning of the force-feeding period and the
concentration of glutamate dehydrogenase, which, in humans, is involved in
increased glucose absorption by the liver when the glutamate dehydrogenase 1 gene
is mutated. CONCLUSIONS: We identified pleiotropic loci that affect metabolic
pathways linked to glycolysis or lipogenesis, and in the end to fatty liver
quality. Further investigation, via transcriptomics and metabolomics approaches,
is required to confirm the biomarkers that were found to impact the genetic
variability of these phenotypic traits.
PMID- 28424048
TI - Phylogeny, divergence time and historical biogeography of Laetiporus
(Basidiomycota, Polyporales).
AB - BACKGROUND: The aim of this study was to characterize the molecular relationship,
origin and historical biogeography of the species in important brown rot fungal
genus Laetiporus from East Asia, Europe, Pan-America, Hawaii and South Africa. We
used six genetic markers to estimate a genus-level phylogeny including (1) the
internal transcribed spacer (ITS), (2) nuclear large subunit rDNA (nrLSU), (3)
nuclear small subunit rDNA (nrSSU), (4) translation elongation factor 1-alpha (EF
1alpha), (5) DNA-directed RNA polymerase II subunit 2 (RPB2), and (6)
mitochondrial small subunit rDNA (mtSSU). RESULTS: Results of multi-locus
phylogenetic analyses show clade support for at least seventeen species-level
lineages including two new Laetiporus in China. Molecular dating using BEAST
estimated the present crown group diverged approximately 20.16 million years ago
(Mya) in the early Miocene. Biogeographic analyses using RASP indicated that
Laetiporus most likely originated in temperate zones with East Asia and North
America having the highest probability (48%) of being the ancestral area.
CONCLUSIONS: Four intercontinental dispersal routes and a possible concealed
dispersal route were established for the first time.
PMID- 28424049
TI - Findings in young adults at colonoscopy from a hospital service database audit.
AB - BACKGROUND: Colorectal cancer (CRC) diagnosed at <50 years is predominantly
located in the distal colon and rectum. Little is known about which lesion
subtypes may serve as CRC precursors in young adults. The aim of this work was to
document the prevalence and histological subtype of lesions seen in patients aged
<50 years, and any associated clinical features. METHODS: An audit of the
colonoscopy database at The Queen Elizabeth Hospital in Adelaide, South Australia
over a 12-month period was undertaken. Findings were recorded from both
colonoscopy reports and corresponding histological examination of excised
lesions. RESULTS: Data were extracted from colonoscopies in 2064 patients. Those
aged <50 comprised 485 (24%) of the total. CRC precursor lesions (including
sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas, tubular
adenomas >=10 mm or with high-grade dysplasia, and conventional adenomas with
villous histology) were seen in 4.3% of patients aged <50 and 12.9% of patients
aged >=50 (P <0.001). Among colonoscopies yielding CRC precursor lesions in
patients under 50 years, SSA/P occurred in 52% of procedures (11/21), compared
with 27% (55/204) of procedures in patients aged 50 and older (P = 0.02). SSA/P
were proximally located in (10/11) 90% of patients aged under 50, and 80% (43/54)
of those aged 50 and older (P = 0.46). CONCLUSIONS: SSA/P were the most
frequently observed CRC precursor lesions in patients aged <50. Most CRCs in this
age group are known to arise in the distal colon and rectum suggesting that
lesions other than SSA/P may serve as the precursor for the majority of early
onset CRC.
PMID- 28424050
TI - In the quest for degenerative lumbar spinal stenosis etiology: the Schmorl's
nodes model.
AB - BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) is a common health problem
in the elderly and usually associated with three-joint complex degeneration.
Schmorl's nodes (SNs) are described as vertical herniation of the disc into the
vertebral body through a weakened part of the end plate that can lead to disc
degeneration. Since SNs can harm the spine unit stability, the association
between DLSS and SNs is expected. The aim of this study is to shed light on the
relationship between degenerative lumbar spinal stenosis and SNs. METHODS: Two
groups of individuals were studied: the first included 165 individuals with DLSS
(age range: 40-88, sex ratio: 80 M/85 F) and the second 180 individuals without
spinal stenosis related symptoms (age range: 40-99, sex ratio: 90 M/90 F). The
presence or absence of SNs on the cranial and caudal end plate surfaces at the
lumbosacral region (from L1 to S1 vertebra) was recorded, using CT images
(Brilliance 64 Philips Medical System, Cleveland Ohio, thickness of the sections
was 1-3 mm and MAS, 80-250). Chi-Square test was taken to compare the prevalence
of SNs between the study groups (control and stenosis) by lumbar disc level, for
each gender separately. Multivariable logistic regression analysis was also used
to determine the association between DLSS and SNs. RESULTS: The prevalence rate
of SNs was significantly greater in the stenosis males (L1-2 to L5-S1) and
females (L4-5 and L4-S1) compared to their counterparts in the control (P <
0.001). In addition, the presence of SNs in both males and females was found to
increase the likelihood for DLSS. CONCLUSIONS: Our results indicate that SNs
prevalence is significantly greater in the DLSS group compared to the control.
Furthermore, SNs are strongly associated with DLSS.
PMID- 28424051
TI - Erratum to: Population seroprevalence of antibody to influenza A(H7N9) virus,
Guangzhou, China.
PMID- 28424052
TI - Using implementation facilitation to foster clinical practice quality and
adherence to evidence in challenged settings: a qualitative study.
AB - BACKGROUND: We evaluated a facilitation strategy to help clinical sites likely to
experience challenges implement evidence-based Primary Care-Mental Health
Integration (PC-MHI) care models within the context of a Department of Veterans
Affairs (VA) initiative. This article describes our assessment of whether
implementation facilitation (IF) can foster development of high quality PC-MHI
programs that adhere to evidence, are sustainable and likely to improve clinical
practices and outcomes. METHODS: Utilizing a matched pair design, we conducted a
qualitative descriptive evaluation of the IF strategy in sixteen VA primary care
clinics. To assess program quality and adherence to evidence, we conducted one
hour structured telephone interviews, at two time points, with clinicians and
leaders who knew the most about the clinics' programs. We then created structured
summaries of the interviews that VA national PC-MHI experts utilized to rate the
programs on four dimensions (overall quality, adherence to evidence,
sustainability and level of improvement). RESULTS: At first assessment, seven of
eight IF sites and four of eight comparison sites had implemented a PC-MHI
program. Our qualitative assessment suggested that experts rated IF sites'
programs higher than comparison sites' programs with one exception. At final
assessment, all eight IF but only five comparison sites had implemented a PC-MHI
program. Again, experts rated IF sites' programs higher than their matched
comparison sites with one exception. Over time, all ratings improved in five of
seven IF sites and two of three comparison sites. CONCLUSIONS: Implementing
complex evidence-based programs, particularly in settings that lack
infrastructure, resources and support for such efforts, is challenging. Findings
suggest that a blend of external expert and internal regional facilitation
strategies that implementation scientists have developed and tested can improve
PC-MHI program uptake, quality and adherence to evidence in primary care clinics
with these challenges. However, not all sites showed these improvements. To be
successful, facilitators likely need at least a moderate level of leaders'
support, including provision of basic resources. Additionally, we found that IF
and strength of leadership structure may have a synergistic effect on ability to
implement higher quality and evidence-based programs.
PMID- 28424053
TI - Stress induced nuclear granules form in response to accumulation of misfolded
proteins in Caenorhabditis elegans.
AB - BACKGROUND: Environmental stress can affect the viability or fecundity of an
organism. Environmental stressors may affect the genome or the proteome and can
cause cellular distress by contributing to protein damage or misfolding. This
study examines the cellular response to environmental stress in the germline of
the nematode, C. elegans. RESULTS: Salt stress, oxidative stress, and starvation,
but not heat shock, induce the relocalization of ubiquitin, proteasome, and the
TIAR-2 protein into distinct subnuclear regions referred to as stress induced
nuclear granules (SINGs). The SINGs form within 1 h of stress initiation and do
not require intertissue signaling. K48-linked polyubiquitin chains but not K63
chains are enriched in SINGs. Worms with a mutation in the conjugating enzyme,
ubc-18, do not form SINGs. Additionally, knockdown of ubc-20 and ubc-22 reduces
the level of SING formation as does knockdown of the ubiquitin ligase chn-1, a
CHIP homolog. The nuclear import machinery is required for SING formation.
Stressed embryos containing SINGs fail to hatch and cell division in these
embryos is halted. The formation of SINGs can be prevented by pre-exposure to a
brief period of heat shock before stress exposure. Heat shock inhibition of SINGs
is dependent upon the HSF-1 transcription factor. CONCLUSIONS: The heat shock
results suggest that chaperone expression can prevent SING formation and that the
accumulation of damaged or misfolded proteins is a necessary precursor to SING
formation. Thus, SINGs may be part of a novel protein quality control system. The
data suggest an interesting model where SINGs represent sites of localized
protein degradation for nuclear or cytosolic proteins. Thus, the physiological
impacts of environmental stress may begin at the cellular level with the
formation of stress induced nuclear granules.
PMID- 28424054
TI - An unusual delusion of duplication in a patient affected by Dementia with Lewy
bodies.
AB - BACKGROUND: Dementia with Lewy bodies (DLB) is the second most frequent diagnosis
of progressive degenerative dementia in older people. Delusions are common
features in DLB and, among them, Capgras syndrome represents the most frequent
disturbance, characterized by the recurrent and transient belief that a familiar
person, often a close family member or caregiver, has been replaced by an
identical-looking imposter. However, other delusional conditions near to
misidentification syndromes can occur in DLB patients and may represent a major
psychiatric disorder, although rarely studied systematically. CASE PRESENTATION:
We reported on a female patient affected by DLB who presented with an unusual
delusion of duplication. Referring to the female professional caregiver engaged
by her relatives for her care, the patient constantly described the presence of
two different female persons, with a disorder framed in the context of a delusion
of duplication. A brain 99Tc-hexamethylpropyleneamineoxime SPECT was performed
showing moderate hypoperfusion in both occipital lobes, and associated with
marked decreased perfusion in parieto-fronto-temporal lobes bilaterally.
CONCLUSIONS: An occipital hypoperfusion was identified, although in association
with a marked global decrease of perfusion in the remaining lobes. The role of
posterior lobes is certainly important in all misidentification syndromes where a
natural dissociation between recognition and identification is present. Moreover,
the concomitant presence of severe attentional and executive deficits evocative
for a frontal syndrome and the marked global decrease of perfusion in the
remaining lobes at the SPECT scan also suggest a possible dysfunction in an
abnormal connectivity between anterior and posterior areas.
PMID- 28424055
TI - How participation in surgical mortality audit impacts surgical practice.
AB - BACKGROUND: Surgical mortality audit is an important tool for quality assurance
and professional development but little is known about the impact of such
activity on professional practice at the individual surgeon level. This paper
reports the findings of a survey conducted with a self-selected cohort of
surgeons in Queensland, Australia, on their experience of participating in the
audit and its impact on their professional practice, as well as implications for
hospital systems. METHODS: The study used a descriptive cross-sectional survey
design. All surgeons registered in Queensland in 2015 (n = 919) were invited to
complete an anonymous online questionnaire between September and October 2015.
184 surgeons completed and returned the questionnaire at a response rate of 20%.
RESULTS: Thirty-nine percent of the participants reported that involvement in the
audit process affected their clinical practice. This was particularly the case
for surgeons whose participation included being an assessor. Thirteen percent of
the participants had perceived improvement to hospital practices or advancement
in patient care and safety as a result of audit recommendations. Analysis of the
open-ended responses suggested the audit experience had led surgeons to become
more cautious, reflective in action and with increased confidence in best
practice, and recognise the importance of effective communication and clear
documentation. CONCLUSIONS: This is the first study to examine the impact of
participation in a mortality audit process on the professional practice of
surgeons. The findings offer evidence for surgical mortality audit as an
effective strategy for continuous professional development and for improving
patient safety initiatives.
PMID- 28424056
TI - Use of multi-trait and random regression models to identify genetic variation in
tolerance to porcine reproductive and respiratory syndrome virus.
AB - BACKGROUND: A host can adopt two response strategies to infection: resistance
(reduce pathogen load) and tolerance (minimize impact of infection on
performance). Both strategies may be under genetic control and could thus be
targeted for genetic improvement. Although there is evidence that supports a
genetic basis for resistance to porcine reproductive and respiratory syndrome
(PRRS), it is not known whether pigs also differ genetically in tolerance. We
determined to what extent pigs that have been shown to vary genetically in
resistance to PRRS also exhibit genetic variation in tolerance. Multi-trait
linear mixed models and random regression sire models were fitted to PRRS Host
Genetics Consortium data from 1320 weaned pigs (offspring of 54 sires) that were
experimentally infected with a virulent strain of PRRS virus to obtain genetic
parameter estimates for resistance and tolerance. Resistance was defined as the
inverse of within-host viral load (VL) from 0 to 21 (VL21) or 0 to 42 (VL42) days
post-infection and tolerance as the slope of the reaction-norm of average daily
gain (ADG21, ADG42) on VL21 or VL42. RESULTS: Multi-trait analysis of ADG
associated with either low or high VL was not indicative of genetic variation in
tolerance. Similarly, random regression models for ADG21 and ADG42 with a
tolerance slope fitted for each sire did not result in a better fit to the data
than a model without genetic variation in tolerance. However, the distribution of
data around average VL suggested possible confounding between level and slope
estimates of the regression lines. Augmenting the data with simulated growth
rates of non-infected half-sibs (ADG0) helped resolve this statistical
confounding and indicated that genetic variation in tolerance to PRRS may exist
if genetic correlations between ADG0 and ADG21 or ADG42 are low to moderate.
CONCLUSIONS: Evidence for genetic variation in tolerance of pigs to PRRS was weak
when based on data from infected piglets only. However, simulations indicated
that genetic variance in tolerance may exist and could be detected if comparable
data on uninfected relatives were available. In conclusion, of the two defense
strategies, genetics of tolerance is more difficult to elucidate than genetics of
resistance.
PMID- 28424057
TI - Personalized medicine in Europe: not yet personal enough?
AB - BACKGROUND: Personalized medicine has the potential to allow patients to receive
drugs specific to their individual disease, and to increase the efficiency of the
healthcare system. There is currently no comprehensive overview of personalized
medicine, and this research aims to provide an overview of the concept and
definition of personalized medicine in nine European countries. METHODS: A
targeted literature review of selected health databases and grey literature was
conducted to collate information regarding the definition, process, use, funding,
impact and challenges associated with personalized medicine. In-depth qualitative
interviews were carried out with experts with health technology assessment,
clinical provisioning, payer, academic, economic and industry experience, and
with patient organizations. RESULTS: We identified a wide range of definitions of
personalized medicine, with most studies referring to the use of diagnostics and
individual biological information such as genetics and biomarkers. Few studies
mentioned patients' needs, beliefs, behaviour, values, wishes, utilities,
environment and circumstances, and there was little evidence in the literature
for formal incorporation of patient preferences into the evaluation of new
medicines. Most interviewees described approaches to stratification and
segmentation of patients based on genetic markers or diagnostics, and few
mentioned health-related quality of life. CONCLUSIONS: The published literature
on personalized medicine is predominantly focused on patient stratification
according to individual biological information. Although these approaches are
important, incorporation of environmental factors and patients' preferences in
decision making is also needed. In future, personalized medicine should move from
treating diseases to managing patients, taking into account all individual
factors.
PMID- 28424058
TI - Family members of deceased palliative care patients receiving bereavement
anniversary cards: a survey on the recipient's reactions and opinions.
AB - BACKGROUND: Bereavement support is part of palliative care. Sending out
bereavement anniversary cards is one intervention of follow-up support for the
bereaved. This study evaluated the suitability of bereavement anniversary cards
as an appropriate method in bereavement care. METHODS: A questionnaire was sent
to each card recipient since the starting point of this practice (October 2014
June 2015). Data was analyzed descriptively. RESULTS: 24 of 68 deliverable
questionnaires were returned (response rate 35%). 22 out of 24 recipients felt
pleased receiving the card. No participant felt annoyed on receiving the
bereavement anniversary card; every participant agreed to at least one positive
reaction (i.e. pleased, grateful or consoled). CONCLUSIONS: The participants'
reactions and opinions about receiving the anniversary card were decidedly
positive and indicate the continuation of this practice. Those few less pleased
reactions may be related to timing and the first anniversary of the patients'
death and therefore an expression of grief rather than a dissatisfaction with
bereavement anniversary cards, as such.
PMID- 28424059
TI - Insight into human pubertal growth by applying the QEPS growth model.
AB - BACKGROUND: Computerized mathematical models describing absolute and relative
individual growth during puberty in both cm and standard deviation (SD)-scores
are lacking. The present study aimed to fill this gap, by applying the QEPS-model
that delineates mathematically the specific pubertal functions of the total
growth curve. METHODS: Study population used was the individual growth curves of
the longitudinally followed cohort GrowUp1974 Gothenburg (n = 2280). The QEPS
model describes total height as (T)otal-function: a combination of four shape
invariant growth functions, modified by time-scale and height-scale parameters: a
(Q)uadratic-function for the continuous growth from fetal life to adulthood; a
negative (E)xponential-function adds the rapid, declining fetal/infancy growth; a
(P)ubertal-function the specific pubertal growth spurt; a (S)top-function the
declining growth until adult height. A constructed variable, MathSelect, was
developed for assessing data-quality. CIs and SD-scores for growth estimates were
calculated for each individual. QEPS-model estimates used for pubertal growth;
from the T-function: onset of puberty as minimal height velocity (AgeT ONSET );
mid-puberty as peak height velocity (AgeT PHV ); end of puberty as height
velocity decreased to 1 cm/year (AgeT END ); duration of different intervals and
gain (AgeT ONSET-END and Tpubgain); from the P-function: onset of puberty,
estimated as growth at 1% or 5% (AgeP1 , AgeP5); mid-puberty as 50% (AgeP50) and
PHV (AgeP PHV ); end of pubertal growth at 95 or 99% (AgeP95, AgeP99); duration
of different intervals and pubertal gain (Ppubgain; P max ); from the QES
function: gain (QESpubgain) . RESULTS: Application of these mathematical
estimates for onset, middle and end of puberty of P-function, QES-function, and T
function during puberty showed: the later the onset of puberty, the greater the
adult height; pubertal gain due to the P-function growth was independent of age
at onset of puberty; boys had higher total gain during puberty due to P-function
growth than to QES-function growth; for girls it was reversed. CONCLUSIONS: QEPS
is the first growth model to provide individualized estimates of both the
specific pubertal growth function and the total growth during puberty, with
accompanying SD-scores and Cis for each individual. These QEPS-derived estimates
enable more in-depth analysis of different aspects of pubertal growth than
previously possible.
PMID- 28424060
TI - Effects of a combination treatment of KD5040 and L-dopa in a mouse model of
Parkinson's disease.
AB - BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l
dopa) remains the gold standard pharmacological therapy for patients with
Parkinson's disease (PD), long-term treatment with this drug has been known to
result in several adverse effects, including l -dopa-induced dyskinesia (LID).
Recently, our group reported that KD5040, a modified herbal remedy, had
neuroprotective effects in both in vitro and in vivo models of PD. Thus, the
present study investigated whether KD5040 would have synergistic effects with l
dopa and antidyskinetic effects caused by l -dopa as well. METHODS: The effects
of KD5040 and l -dopa on motor function, expression levels of substance P (SP)
and enkephalin (ENK) in the basal ganglia, and glutamate content in the motor
cortex were assessed using behavioral assays, immunohistochemistry, Western blot
analyses, and liquid chromatography tandem mass spectrometry in a mouse model of
PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In addition,
the antidyskinetic effects of KD5040 on pathological movements triggered by l
dopa were investigated by testing abnormal involuntary movements (AIMs) and
measuring the activations of FosB, cAMP-dependent phosphor protein of 32 kDa
(DARPP-32), extracellular signal-regulated kinases (ERK), and cAMP response
element-binding (CREB) protein in the striatum. RESULTS: KD5040 synergistically
improved the motor function when low-dose l -dopa (LL) was co-administered. In
addition, it significantly reversed MPTP-induced lowering of SP, improved ENK
levels in the basal ganglia, and ameliorated abnormal reduction in glutamate
content in the motor cortex. Furthermore, KD5040 significantly lowered AIMs and
controlled abnormal levels of striatal FosB, pDARPP-32, pERK, and pCREB induced
by high-dose l -dopa. CONCLUSIONS: KD5040 lowered the effective dose of l -dopa
and alleviated LID. These findings suggest that KD5040 may be used as an adjunct
therapy to enhance the efficacy of l -dopa and alleviate its adverse effects in
patients with PD.
PMID- 28424061
TI - Young people, mental health practitioners and researchers co-produce a Transition
Preparation Programme to improve outcomes and experience for young people leaving
Child and Adolescent Mental Health Services (CAMHS).
AB - BACKGROUND: In the UK young people attending child and adolescent mental health
services (CAMHS) are required to move on, either through discharge or referral to
an adult service, at age 17/18, a period of increased risk for onset of mental
health problems and other complex psychosocial and physical changes. CAMHS
transitions are often poorly managed with negative outcomes for young people.
Better preparation may improve outcomes and experience. This study aimed to co
produce, with young people who had transitioned or were facing transition from
CAMHS, a CAMHS Transition Preparation Programme (TPP), deliverable in routine NHS
settings. METHODS: Eighteen young people, aged 17-22, from three UK National
Health Service (NHS) mental health foundation trusts participated in creative,
participatory research workshops. Seven parents completed short questionnaires.
Thirty clinical staff from two trusts took part in workshops to ensure
deliverability of young people's ideas. Young people were offered co-research
opportunities. RESULTS: Most young people felt anxious, fearful and uncertain on
leaving CAMHS and perceived mental health services as uncaring. Participants
outlined transition procedures and drafted a range of preparation activities,
centred around dedicated Transition Peer Support and a transition booklet, which
should be offered to all CAMHS leavers, irrespective of discharge or transfer to
an adult service. Preparation should aim to build confidence to help young people
take responsibility for themselves and flourish in the adult world: coping or
getting through it was not enough. Some clinicians also felt anxious at
transition and recognised the potential impact on young people of poor
communication and lack of understanding between services. Parents would
appreciate help to support their offspring during the transition period.
Clinicians cited lack of funding and inflexible NHS procedures and policies as
potential barriers to the implementation of young people's ideas. Nine young
people took up co-research opportunities. CONCLUSIONS: Mental health services
underestimate the anxiety of CAMHS leavers. Young people have clear ideas about
the preparation they require to leave CAMHS with the confidence to take
responsibility for their own health care. Close collaboration of NHS staff and
researchers facilitates the implementation of research findings.
PMID- 28424062
TI - Health system factors influencing management of multidrug-resistant tuberculosis
in four European Union countries - learning from country experiences.
AB - BACKGROUND: In the European Union and European Economic Area only 38% of
multidrug-resistant tuberculosis patients notified in 2011 completed treatment
successfully at 24 months' evaluation. Socio-economic factors and patient factors
such as demographic characteristics, behaviour and attitudes are associated with
treatment outcomes. Characteristics of healthcare systems also affect health
outcomes. This study was conducted to identify and better understand the
contribution of health system components to successful treatment of multidrug
resistant tuberculosis. METHODS: We selected four European Union countries to
provide for a broad range of geographical locations and levels of treatment
success rates of the multidrug-resistant tuberculosis cohort in 2009. We
conducted semi-structured interviews following a conceptual framework with
representatives from policy and planning authorities, healthcare providers and
civil society organisations. Responses were organised according to the six
building blocks of the World Health Organization health systems framework.
RESULTS: In the four included countries, Austria, Bulgaria, Spain, and the United
Kingdom, the following healthcare system factors were perceived as key to
achieving good treatment results for patients with multidrug-resistant
tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems
that ensure access to a full course of treatment and support for multidrug
resistant tuberculosis patients; patient-centred approaches with strong
intersectoral collaboration that address patients' emotional and social needs;
motivated and dedicated healthcare workers with sufficient mandate and means to
support patients; and cross-border management of multidrug-resistant tuberculosis
to secure continuum of care between countries. CONCLUSION: We suggest that the
following actions may improve the success of treatment for multidrug-resistant
tuberculosis patients: deployment of rapid molecular diagnostic tests;
development of context-specific treatment guidance and criteria for hospital
admission and discharge in the European context; strengthening patient-centred
approaches; development of collaborative mechanisms to ensure cross-border care,
and development of long-term sustainable financing strategies.
PMID- 28424063
TI - Clinical and cost-effectiveness analysis of early detection of patients at
nutrition risk during their hospital stay through the new screening method CIPA:
a study protocol.
AB - BACKGROUND: Malnutrition is highly prevalent in hospitalized patients and results
in a worsened clinical course as well as an increased length of stay, mortality,
and costs. Therefore, simple nutrition screening systems, such as CIPA (control
of food intake, protein, anthropometry), may be implemented to facilitate the
patient's recovery process. The aim of this study is to evaluate the
effectiveness and cost-effectiveness of implementing such screening tool in a
tertiary hospital, consistent with the lack of similar, published studies on any
hospital nutrition screening system. METHODS: The present study is carried out as
an open, controlled, randomized study on patients that were admitted to the
Internal Medicine and the General and Digestive Surgery ward; the patients were
randomized to either a control or an intervention group (n = 824, thereof 412
patients in each of the two study arms). The control group underwent usual
inpatient clinical care, while the intervention group was evaluated with the CIPA
screening tool for early detection of malnutrition and treated accordingly. CIPA
nutrition screening was performed upon hospital admission and classified positive
when at least one of the following parameters was met: 72 h food intake control <
50%, serum albumin < 3 g/dL, body mass index < 18.5 kg/m2 (or mid-upper arm
circumference <= 22.5 cm). In this case, the doctor decided on whether or not
providing nutrition support. The following variables will be evaluated: hospital
length of stay (primary endpoint), mortality, 3-month readmission, and in
hospital complications. Likewise, the quality of life questionnaires EQ-5D-5 L
are being collected for all patients at hospital admission, discharge, and 3
months post-discharge. Analysis of cost-effectiveness will be performed by
measuring effectiveness in terms of quality-adjusted life years (QALYs). The cost
per patient will be established by identifying health care resource utilization;
cost-effectiveness will be determined through the incremental cost-effectiveness
ratio (ICER). We will calculate the incremental cost per QALY gained with respect
to the intervention. DISCUSSION: This ongoing trial aims to evaluate the cost
effectiveness of implementing the malnutrition screening tool CIPA in a tertiary
hospital. TRIAL REGISTRATION: Clinical Trial.gov ( NCT02721706 ). First
receivevd: March 1, 2016 Last updated: April 8, 2017 Last verified: April 2017.
PMID- 28424064
TI - Effectiveness of triple therapy with direct-acting antivirals for hepatitis C
genotype 1 infection: application of propensity score matching in a national HCV
treatment registry.
AB - BACKGROUND: Observational studies are used to measure the effectiveness of an
intervention in non-experimental, real world scenarios at the population level
and are recognised as an important component of the evidence pyramid. Such data
can be accrued through prospective cohort studies and a patient registry is a
proven method for this type of study. The national hepatitis C (HCV) registry was
established in Ireland in 2012 with the aim of monitoring the clinical and
economic outcomes from new, high cost regimens for the treatment of HCV
infection. A sustained virological response (SVR) 24 weeks following completion
of therapy with interferon-containing regimens is considered a cure. Non
randomisation in these studies can result in confounding or selection bias.
Propensity score (PS) matching is one of a number of statistical tools that can
be used to mitigate the effects of confounding in observational studies. METHODS:
We analysed the data of 309 patients who underwent triple therapy treatment with
telaprevir (TPV) in combination with pegylated-interferon and ribavirin (PR) or
boceprevir (BOC)/PR between June 2012 and December 2014. The decision to initiate
treatment and the selection of the treatment regimen was at the discretion of the
physician. To adjust for confounding, three approaches to propensity score
matching were assessed Adjusted sustained-virological response rates (SVR), odds
ratios, p-values and 95% confidence intervals were calculated from the three PS
matched dataset. RESULTS: Prior to matching, the unadjusted sustained virological
response rates 24 weeks after treatment complete (SVR24) were 74% (n = 158/215)
and 61% (n = 57/94) for telaprevir/PR and boceprevir/PR, respectively. After
matching, adjusted SVR24 rates were between 73-74% and 60-61% for telaprevir/PR
and boceprevir/PR, respectively. CONCLUSION: Efficacy rates were comparable with
those reported in pivotal clinical trials and real world studies. After adjusting
for confounding, we conclude that there was no difference in treatment effect
after PS matching. The small sample size limits the conclusions that can be made
about the effect of PS matching. Propensity score adjustment remains a tool that
can be applied to future analysis, however, we suggest, where possible, using a
larger sample size in order to reduce the uncertainty around the outcomes.
PMID- 28424065
TI - Efficacy of irreversible EGFR-TKIs for the uncommon secondary resistant EGFR
mutations L747S, D761Y, and T854A.
PMID- 28424066
TI - Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA
methylation and lung function decrements among urban children.
AB - BACKGROUND: Both short and long-term exposure to traffic-related air pollutants
have been associated with asthma and reduced lung function. We hypothesized that
short-term indoor exposure to fine particulate matter <2.5 MUm (PM2.5) and
vanadium (V) would be associated with altered buccal cell DNA methylation of
targeted asthma genes and decreased lung function among urban children in a
nested subcohort of African American and Dominican children. METHODS: Six day
integrated levels of air pollutants were measured from children's homes (age 9
14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected
repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4
(IL4), interferon gamma (IFNgamma), inducible nitric oxide synthase (NOS2A),
arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. RESULTS:
Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4
and IFNgamma. In exploratory analyses, V levels were associated with lower
methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or
obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V,
appeared associated with lower lung function (i.e., reduced z-scores for forced
expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and
forced expiratory flow at 25-75% of FVC [FEF25-75]). CONCLUSIONS: Exposure to V
was associated with altered DNA methylation of allergic and proinflammatory
asthma genes implicated in air pollution related asthma. However, short-term
exposure to PM2.5, but not V, appeared associated with decrements in lung
function among urban children.
PMID- 28424067
TI - Preventing parastomal hernias with systematic intraperitoneal specifically
designed mesh.
AB - BACKGROUND: Parastomal hernia is a very common complication after stoma
formation. Current surgical techniques for repairing parastomal hernia have
unsatisfactory results. We aim to assess our preliminary experience with
prophylactic mesh placement at the time of stoma formation. METHODS: Data were
prospectively recorded. A specifically designed mesh made of polyvinyl fluoride
with central conduit (Dynamesh IPST(r)) was fixed using an intra-peritoneal onlay
technique. Safety was evaluated by means of surgical data and frequency of mesh
related complications, efficacy by the rate of parastomal hernias. RESULTS:
Thirty-four patients were included in the study. Three of them died before a year
of follow up (not related to the stoma), so they were excluded. The other 31
patients (11 women and 20 men) were prospectively followed up after different
pathologies resulting in a permanent colostomy. Twelve months after surgery CT
Scan imaging revealed two (6.4%) parastomal hernias, one of them already
clinically suspected. During the follow up, 29% of the patients (n = 9) developed
another type of hernia (incisional, inguinal or both). In five patients (16.1%) a
light stomal retraction of the otherwise slightly prominent ostomy was observed.
Median clinical follow-up was 17.5 months (range 12-34). CONCLUSION: Prophylactic
parastomal mesh placement might be a safe and effective procedure with a
potential to reduce the risk of parastomal hernia. Routine use of this technique
should be further analysed.
PMID- 28424068
TI - Efficacy of a Transdiagnostic internet-based treatment for emotional disorders
with a specific component to address positive affect: Study protocol for a
randomized controlled trial.
AB - BACKGROUND: Emotional disorders (ED) are among the most prevalent mental
disorders. However, less than 50% of people suffering from ED receive the
appropriate treatment. This situation has led to the development of new
intervention proposals based on the transdiagnostic perspective, which tries to
address the underlying processes common to ED. Most of these programs focus
primarily on down-regulating negative affectivity, rather than increasing
strengths and up-regulating positive affectivity. The data suggest the existence
of disturbances in positive affectivity in these disorders, and so new
interventions focusing on these problems are greatly needed. It is also essential
to provide assistance to all the people in need. Information and Communication
Technologies can be very useful. This study aims to evaluate the efficacy of a
transdiagnostic Internet-based treatment for ED in a community sample. The
protocol includes traditional CBT components, as well as a specific component to
address positive affect. We intend to test this protocol, including this specific
component or not, versus a waiting list control group. Moreover, we aim to test
the differential effect of this specific component, and study the effectiveness
(in terms of patients' acceptance) of using a self-applied Internet-based
program. This paper presents the study protocol. METHODS: The study is a
randomized controlled trial. 207 participants will be randomly assigned to:
a)Transdiagnostic Internet-based protocol (TIBP), b)Transdiagnostic Internet
based protocol + positive affect component (TIBP + PA), or c)a Waiting List
control group (WL). Primary outcomes measures will be the BDI-II, the BAI, and
the PANAS. Secondary outcomes will include diagnosis-specific measures of the
principal disorder. Participants' treatment acceptance will also be measured.
Participants will be assessed at pre-, post-treatment, and 3- and 12- month
follow-ups. The data will be analyzed based on the Intention-to-treat principle.
Per protocol analyses will also be performed. DISCUSSION: To the best of our
knowledge, this is the first study of a transdiagnostic Internet-based treatment
for ED with a specific component to up-regulate positive affectivity. This
intervention could contribute to improve the efficiency and effectiveness of
current treatment programs for ED, promote the dissemination of EBTs, and help to
decrease the high prevalence of ED. TRIAL REGISTRATION: ClinicalTrial.gov:
NCT02578758 . Registered 15 October 2015.
PMID- 28424069
TI - AnkPlex: algorithmic structure for refinement of near-native ankyrin-protein
docking.
AB - BACKGROUND: Computational analysis of protein-protein interaction provided the
crucial information to increase the binding affinity without a change in basic
conformation. Several docking programs were used to predict the near-native poses
of the protein-protein complex in 10 top-rankings. The universal criteria for
discriminating the near-native pose are not available since there are several
classes of recognition protein. Currently, the explicit criteria for identifying
the near-native pose of ankyrin-protein complexes (APKs) have not been reported
yet. RESULTS: In this study, we established an ensemble computational model for
discriminating the near-native docking pose of APKs named "AnkPlex". A dataset of
APKs was generated from seven X-ray APKs, which consisted of 3 internal domains,
using the reliable docking tool ZDOCK. The dataset was composed of 669 and 44,334
near-native and non-near-native poses, respectively, and it was used to generate
eleven informative features. Subsequently, a re-scoring rank was generated by
AnkPlex using a combination of a decision tree algorithm and logistic regression.
AnkPlex achieved superior efficiency with >=1 near-native complexes in the 10 top
rankings for nine X-ray complexes compared to ZDOCK, which only obtained six X
ray complexes. In addition, feature analysis demonstrated that the van der Waals
feature was the dominant near-native pose out of the potential ankyrin-protein
docking poses. CONCLUSION: The AnkPlex model achieved a success at predicting
near-native docking poses and led to the discovery of informative characteristics
that could further improve our understanding of the ankyrin-protein complex. Our
computational study could be useful for predicting the near-native poses of
binding proteins and desired targets, especially for ankyrin-protein complexes.
The AnkPlex web server is freely accessible at http://ankplex.ams.cmu.ac.th .
PMID- 28424070
TI - Antidepressant use and cognitive decline in community-dwelling elderly people -
The Three-City Cohort.
AB - BACKGROUND: Cognitive impairment is very common in late-life depression,
principally affecting executive skills and information processing speed. The aim
of the study was to examine the effect of antidepressant treatment on cognitive
performances over a 10-year period. METHODS: The community-based cohort included
7381 participants aged 65 years and above. Five cognitive domains (verbal
fluency, psychomotor speed, executive function, visuospatial skills and global
cognition) were assessed up to five times over 10 years of follow-up. Treatment
groups included participants under a specific antidepressant class at both
baseline and the first follow-up and their follow-up cognitive data were
considered until the last consecutive follow-up with a report of antidepressant
use of the same class. Linear mixed models were used to compare baseline
cognitive performance and cognitive decline over time according to antidepressant
treatment. The models were adjusted for multiple confounders including residual
depressive symptoms assessed by the Center for Epidemiologic Studies-Depression
scale. RESULTS: At baseline, 4.0% of participants were taking antidepressants.
Compared to non-users, tricyclic antidepressant users had lower baseline
performances in verbal fluency, visual memory and psychomotor speed, and
selective serotonin reuptake inhibitor users in verbal fluency and psychomotor
speed. For the two other cognitive abilities, executive function and global
cognition, no significant differences were found at baseline irrespective of the
antidepressant class. Regarding changes over time, no significant differences
were observed in comparison with non-users whatever the cognitive domain, except
for a slight additional improvement over the follow-up in verbal fluency skills
for tricyclic antidepressant users. CONCLUSIONS: In this large elderly general
population cohort, we found no evidence for an association between antidepressant
use and post-treatment cognitive decline over 10 years of follow-up in various
cognitive domains.
PMID- 28424071
TI - Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a
proof-of-concept study in the preoperative window period (ImPACCT).
AB - BACKGROUND: The identification of four Consensus Molecular Subtypes (CMS1-4) of
colorectal cancer forms a new paradigm for the design and evaluation of subtype
directed therapeutic strategies. The most aggressive subtype - CMS4 - has the
highest chance of disease recurrence. Novel adjuvant therapies for patients with
CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by
expression of mesenchymal and stem-like genes. Previous pre-clinical work has
shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the
related KIT receptor with imatinib is potentially effective against mesenchymal
type colon cancer. In the present study we aim to provide proof for the concept
that imatinib can reduce the aggressive phenotype of primary CMS4 colon cancer.
METHODS: Tumour biopsies from patients with newly diagnosed stage I-III colon
cancer will be analysed with a novel RT-qPCR test to pre-select patients with
CMS4 tumours. Selected patients (n = 27) will receive treatment with imatinib
(400 mg per day) starting two weeks prior to planned tumour resection. To assess
treatment-induced changes in the aggressive CMS4 phenotype, RNA sequencing will
be performed on pre- and post-treatment tissue samples. DISCUSSION: The
development of effective adjuvant therapy for primary colon cancer is hindered by
multiple factors. First, new drugs that may have value in the prevention of
(early) distant recurrence are almost always first tested in patients with
heavily pre-treated metastatic disease. Second, measuring on-target drug effects
and biological consequences in tumour tissue is not commonly a part of the study
design. Third, due to the lack of patient selection tools, clinical trials in the
adjuvant setting require large patient populations. Finally, the evaluation of
recurrence-prevention requires a long-term follow-up. In the ImPACCT trial these
issues are addressed by including newly diagnosed pre-selected patients with CMS4
tumours prior to primary tumour resection, rather than non-selected patients with
late-stage disease. By making use of the pre-operative window period, the
biological effect of imatinib treatment on CMS4 tumours can be rapidly assessed.
Delivering proof-of-concept for drug action in early stage disease should form
the basis for the design of future trials with subtype-targeted therapies in
colon cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02685046 .
Registration date: February 9, 2016.
PMID- 28424072
TI - Prevalence of intimate partner violence and its association with symptoms of
depression; a cross-sectional study based on a female population sample in
Sweden.
AB - BACKGROUND: Intimate Partner Violence (IPV) is the most common type of violence
targeting women. IPV includes acts of physical aggression, sexual coercion,
psychological abuse and controlling behaviors and these forms of violence often
coexist in the same relationship. Living with IPV is associated with serious
mental health outcomes such as depression and depressive symptoms. Few population
based studies from Sweden have investigated the relationship between different
forms of IPV and women's depressive symptoms and even fewer used controlling
behavior as an independent variable in such studies. The aim of this study was
therefore to assess the prevalence of exposure to IPV in terms of controlling
behavior, sexual, and physical violence and their association with self-reported
symptoms of depression in a female population based sample. METHODS: The cross
sectional, population based sample contained 573 women aged 18-65 years randomly
selected in Sweden. Five self-reported symptoms that define depression in the
Diagnostic and Statistical Manual of Mental Disorders were assessed. Physical and
sexual violence were inquired about using the World Health Organization's (WHO)
Violence Against Women Instrument (VAWI), while controlling behavior was assessed
with the Controlling Behavior Scale (CBS). Associations between different forms
of IPV and symptoms of depression were estimated by crude and adjusted odds ratio
(OR) with 95% confidence intervals (CI). RESULTS: Bivariable associations
revealed that women exposed to controlling behavior, had higher OR of depressive
symptoms compared to unexposed women (OR 2.43; 95% CI 1.63-3.63). Women exposed
to physical and sexual violence had also a higher OR of depressive symptoms (OR
3.78; 95% CI 1.99-7.17 and OR 5.10; 95% CI 1.74-14.91 respectively). After
adjusting for socio-demographic and psychosocial covariates, all three forms of
IPV showed statistically significant associations with self-reported symptoms of
depression. CONCLUSIONS: A strength with this study is the analysis of
controlling behavior and its association with self-reported symptoms of
depression in a female population based sample. Exposure to controlling behavior,
physical and sexual violence by an intimate partner were clearly associated with
women's self-reported symptoms of depression.
PMID- 28424073
TI - Systematic review with network meta-analysis: dual therapy for high-risk bleeding
peptic ulcers.
AB - BACKGROUND: Adding a second endoscopic therapy to epinephrine injection might
improve hemostatic efficacy in patients with high-risk bleeding ulcers but the
optimum modality remains unknown. We aimed to estimate the comparative efficacy
of different dual endoscopic therapies for the management of bleeding peptic
ulcers through random-effects Bayesian network meta-analysis. METHODS: Different
databases were searched for controlled trials comparing dual therapy versus
epinephrine monotherapy or epinephrine combined with another second modality
until September, 30 2016. We estimated the ORs for rebleeding, surgery and
mortality among different treatments. Adverse events were also evaluated.
RESULTS: Seventeen eligible articles were included in the network meta-analysis.
The addition of mechanical therapy (OR 0.19, 95% CrI 0.07-0.52 and OR 0.10, 95%
CrI 0.01-0.50, respectively) after epinephrine injection significantly reduced
the probability of rebleeding and surgery. Similarly, patients who received
epinephrine plus thermal therapy showed a significantly decreased rebleeding rate
(OR 0.30, 95% CrI 0.10-0.91), as well as a non-significant reduction in surgery
(OR 0.47, 95% CrI 0.16-1.20). Although differing, epinephrine plus mechanical
therapy did not provide a significant reduction in rebleeding (OR 0.62, 95% CrI
0.19-2.22) and surgery (OR 0.21, 95% CrI 0.03-1.73) compared to epinephrine plus
thermal therapy. Sclerosant failed to confer further benefits and was ranked
highest among the 5 treatments in relation to adverse events. CONCLUSIONS:
Mechanical therapy was the most appropriate modality to add to epinephrine
injection. Epinephrine plus thermal coagulation was effective for controlling
high risk bleeding ulcers. There was no further benefit with sclerosants with
regard to rebleeding or surgery, and sclerosants were also associated with more
adverse events than any other modality.
PMID- 28424074
TI - Implementation and adaptation of the Re-Engineered Discharge (RED) in five
California hospitals: a qualitative research study.
AB - BACKGROUND: Project Re-Engineered Discharge (RED) is an evidence-based strategy
to reduce readmissions disseminated and adapted by various health systems across
the country. To date, little is known about how adapting Project RED from its
original protocol impacts RED implementation and/or sustainability. The goal of
this study was to identify and characterize contextual factors influencing how
five California hospitals adapted and implemented RED and the subsequent impact
on RED program sustainability. METHODS: Participant observation and key informant
and focus group interviews with 64 individuals at five California hospitals
implementing RED in 2012 and 2013 were conducted. These involved hospital
leadership, personnel responsible for Project RED implementation, hospital staff,
and clinicians. Interview transcripts were coded and analyzed using a modified
grounded theory approach and constant comparative analysis. RESULTS: Both
internal and external contextual factors were identified that influenced
hospitals' decisions on RED adaptation and implementation. These also impacted
RED sustainability. External factors included: impending federal penalties for
hospitals with high readmission rates targeting specific diagnoses, and access to
external funding and technical support to help hospitals implement RED. Internal
or organizational level contextual factors included: committed leadership
prioritizing Project RED; RED adaptations; depth, accountability and influence of
the implementation team; sustainability planning; and hospital culture. Only
three of the five hospitals continued Project RED beyond the implementation
period. CONCLUSIONS: The sustainability of RED in participating hospitals was
only possible when hospitals approached RED implementation as a transformational
process rather than a patient safety project, maintained a high level of fidelity
to the RED protocol, and had leadership and an implementation team who embraced
change and failure in the pursuit of better patient care and outcomes. Hospitals
who were unsuccessful in implementing a sustainable RED process lacked all or
most of these components in their approach.
PMID- 28424075
TI - Computational modeling of airway instability and collapse in tracheomalacia.
AB - BACKGROUND: Tracheomalacia (TM) is a condition of excessive tracheal collapse
during exhalation. Both acquired and congenital forms of TM are believed to
result from morphological changes in cartilaginous, fibrous and/or smooth muscle
tissues reducing airway mechanical properties to a degree that precipitates
collapse. However, neither the specific amount of mechanical property reduction
nor the malacic segment lengths leading to life threatening airway collapse in TM
are known. Furthermore, the specific mechanism of collapse is still debated.
METHODS: Computational nonlinear finite element models were developed to
determine the effect of malacic segment length, tracheal diameter, and reduction
in tissue nonlinear elastic properties on the risk for and mechanism of airway
collapse. Cartilage, fibrous tissue, and smooth muscle nonlinear elastic
properties were fit to experimental data from preterm lambs from the literature.
These elastic properties were systematically reduced in the model to simulate TM.
RESULTS: An intriguing finding was that sudden mechanical instability leading to
complete airway collapse occurred in airways when even a 1 cm segment of
cartilage and fibrous tissue properties had a critical reduction in material
properties. In general, increased tracheal diameter, increased malacic segment
length coupled with decreased nonlinear anterior cartilage/fibrous tissue
nonlinear mechanical properties increased the risk of sudden airway collapse from
snap through instability. CONCLUSION: Modeling results support snap through
instability as the mechanism for life threatening tracheomalacia specifically
when cartilage ring nonlinear properties are reduced to a range between fibrous
tissue nonlinear elastic properties (for larger diameter airways > 10 mm) to
mucosa properties (for smaller diameter airways < 6 mm). Although reducing
posterior tracheal smooth muscle properties to mucosa properties decreased
exhalation area, no sudden instability leading to collapse was seen in these
models.
PMID- 28424076
TI - Caregiver's quality of life and its positive impact on symptomatology and quality
of life of patients with schizophrenia.
AB - BACKGROUND: Although the quality of life (QoL) experienced by patients with
schizophrenia has been recognized, few studies have assessed the relationship
between the caregivers' QoL and patients' QoL. METHODS: The study included 253
stabilized outpatients with schizophrenia and their caregivers from 3 Mental
Health Services in Bolivia (N = 83), Chile (N = 85) and Peru (N = 85).
Caregivers' and patients' QoL were respectively assessed using two specific QoL
questionnaires (S-CGQoL and S-QoL 18). We collected socio-demographic information
and clinical data. Multiple linear regressions were performed to determine which
variables were associated with patient's QoL. We tested the following hypothesis
using structural equation modeling (SEM): caregivers' QoL may have an indirect
effect on patients' QoL mediated by their influence of the severity of psychotic
symptoms. RESULTS: In the multivariate analysis, the caregivers' QoL was not
significantly associated with the patients' QoL, except for one QoL dimension
about relationship with family (Beta = 0.23). Among patients' characteristics,
being a woman and Aymara, having lower educational level, unemployment and
severity of symptoms was significantly associated to a lower QoL. The SEM
revealed a moderate significant association between caregivers' QoL and psychotic
symptoms severity (path coefficient = -0.32) and a significant association
between psychotic symptoms severity and patients QoL (path coefficient = -0.40).
The indirect effect of caregivers' QoL on patients' QoL was significant (mediated
effect coefficient = 0.13). CONCLUSION: Improvement of caregiver's QoL may have a
direct impact on the psychotic symptoms of patients and indirectly on patient's
QoL, confirming the need for ongoing family interventions in these regions.
PMID- 28424077
TI - Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia.
AB - BACKGROUND: Metabolomics is a tool that has been used for the diagnosis and
prognosis of specific diseases. The purpose of this study was to examine if
metabolomics could be used as a potential diagnostic and prognostic tool for H1N1
pneumonia. Our hypothesis was that metabolomics can potentially be used early for
the diagnosis and prognosis of H1N1 influenza pneumonia. METHODS: 1H nuclear
magnetic resonance spectroscopy and gas chromatography-mass spectrometry were
used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated
control subjects in the intensive care unit (ICU), and 30 culture-positive plasma
samples from patients with bacterial community-acquired pneumonia drawn within
the first 24 h of hospital admission for diagnosis and prognosis of disease.
RESULTS: We found that plasma-based metabolomics from samples taken within 24 h
of hospital admission can be used to discriminate H1N1 pneumonia from bacterial
pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover,
metabolomics is a highly sensitive and specific tool for the 90-day prognosis of
mortality in H1N1 pneumonia. CONCLUSIONS: This study demonstrates that H1N1
pneumonia can create a quite different plasma metabolic profile from bacterial
culture-positive pneumonia and ventilated control subjects in the ICU on the
basis of plasma samples taken within 24 h of hospital/ICU admission, early in the
course of disease.
PMID- 28424079
TI - Erratum to: Rhodococcus erythropolis as a host for expression, secretion and
glycosylation of Mycobacterium tuberculosis proteins.
PMID- 28424078
TI - Interleukin-6 displays lung anti-inflammatory properties and exerts protective
hemodynamic effects in a double-hit murine acute lung injury.
AB - BACKGROUND: Interleukin 6 (IL-6) is a predictive factor of poor prognosis in
patients with acute respiratory distress syndrome (ARDS). However, its acute
pulmonary hemodynamic effects and role in lung injury have not been investigated
in a clinically relevant murine model of ARDS. METHODS: We used adult C57Bl6 wild
type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous
recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal
lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical
ventilation (MV) for 5 h. Before sacrifice, right ventricular systolic pressure
and cardiac output were measured and total pulmonary resistance was calculated.
After sacrifice, lung inflammation, edema and injury were assessed with
bronchoalveolar lavage (BAL) and histology. In other experiments, right
ventricular systolic pressure was recorded during hypoxic challenges in uninjured
WT mice pretreated with rHuIL-6 or rHuIL-6 + non-selective nitric oxide synthase
inhibitor L-NAME or vehicle. RESULTS: IL-6KO(LPS+MV) mice showed a faster
deterioration of lung elastic properties and more severe bronchoalveolar cellular
inflammation as compared to WT(LPS+MV). Treatment with rHuIL-6 partially
prevented this lung deterioration. Total pulmonary resistance was higher in IL
6KO(LPS+MV) mice and this increase was abolished in rHuIL-6-treated IL-6KO mice.
Finally, rHuIL-6 reduced hypoxic pulmonary vasoconstriction in uninjured WT mice,
an effect that was abolished by co-treatment with L-NAME. CONCLUSIONS: In a
double-hit murine model of ARDS, IL-6 deficient mice experienced more severe
bronchoalveolar cellular inflammation as compared to wild-type littermates.
Furthermore, IL-6 deficiency caused marked acute pulmonary hypertension, which
may be, at least partially, due to vasoactive mechanisms. A dysregulation of
nitric oxide synthase may account for this observation, a hypothesis that will
need to be investigated in future studies.
PMID- 28424080
TI - Erratum to: HDAC6 activity is a non-oncogene addiction hub for inflammatory
breast cancers.
PMID- 28424081
TI - Menu-engineering in restaurants - adapting portion sizes on plates to enhance
vegetable consumption: a real-life experiment.
AB - BACKGROUND: The aim of this research was to investigate whether increased portion
sizes of vegetables and decreased portion sizes of meat on main dishes increased
the amount of vegetables consumed in a real-life restaurant setting without
affecting customer satisfaction. The participants were unaware of the experiment.
METHODS: A cross-over design was used in which three restaurants were randomly
assigned to a sequence of an intervention and control condition. In the
intervention period, the vegetable portion sizes on the plates of main dishes
were doubled (150 g of vegetables instead of 75 g) and the portion sizes of meat
on the plates were reduced by an average of 12.5%. In the control period, the
portion sizes of the main dishes were maintained as usual. In total, 1006
observations and questionnaires were included. RESULTS: Vegetable consumption
from plates was significantly higher during the intervention period (M = 115.5 g)
than during the control period (M = 61.7 g). Similarly, total vegetable
consumption (including side dishes) was significantly higher during the
intervention period (M = 178.0 g) than during the control period (M = 137.0 g).
Conversely, meat consumption was significantly lower during the intervention
period (M = 183.1 g) than during the control period (M = 211.1 g). Satisfaction
with the restaurant visit did not differ between the intervention period (M =
1.27) and control period (M = 1.35). Satisfaction with the main dish was
significantly lower during the intervention period (M = 1.25) than during the
control period (M = 1.38), although in both cases, the scores indicated that
participants remained (very) satisfied with their main dish. CONCLUSIONS: This
study showed that increasing vegetable portions in combination with decreasing
meat portions (unknowingly to the consumer) increased the amount of vegetables
consumed and decreased the amount of meat consumed. Furthermore, despite the
changes in portion sizes, participants remained satisfied with their restaurant
visit and main dish. The findings of this study suggest that modifying portion
size in restaurants is an effective tool for stimulating vegetable consumption
and consequently healthy and sustainable diets.
PMID- 28424083
TI - Erratum to: The impact of co-infections on fish: a review.
PMID- 28424082
TI - Subventricular zones: new key targets for glioblastoma treatment.
AB - BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic
factors of survival and patterns of recurrence among patients with glioblastoma.
METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our
Cancer Center between 2006 and 2010 were identified. All patients received
surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral
(iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively
segmented and radiation dose-volume histograms were generated. Multivariate
analysis using the Cox proportional hazards model was assessed to examine the
relationship between prognostic factors and time to progression (TTP) or overall
survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up,
OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5
26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate
analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs
41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose
bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a
significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation
dose coverage was compatible with an hippocampal sparing. On multivariate
analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor
prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047,
respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as
insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor
prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest
for optimizing glioblastoma treatment.
PMID- 28424084
TI - Durable complete remission with aromatase inhibitor therapy in a patient with
metastatic uterine carcinosarcoma with poor performance status and coagulation
disorders: a case report.
AB - BACKGROUND: Chemotherapy is considered the most appropriate treatment for
metastatic uterine sarcoma, despite its limited efficacy. No other treatment has
been conclusively proved to be a real alternative, but some reports suggest that
anti-hormonal therapy could be active in a small subset of patients. We report
the case of a patient with metastatic uterine carcinosarcoma with positive
hormonal receptors and a complete pathological response. CASE PRESENTATION: A 54
year-old white woman presented to our emergency room with hypovolemic shock and
serious vaginal bleeding. After stabilization, she was diagnosed as having a
locally advanced uterine carcinosarcoma with lymph nodes and bone metastatic
disease. In order to control the bleeding, palliative radiotherapy was
administered. Based on the fact that positive hormone receptors were found in the
biopsy, non-steroidal aromatase inhibitor therapy with letrozole was started. In
the following weeks, her general status improved and restaging imaging tests
demonstrated a partial response of the primary tumor. Ten months after initiating
aromatase inhibitor therapy, she underwent a radical hysterectomy and the
pathological report showed a complete response. After completing 5 years of
treatment, aromatase inhibitor therapy was stopped. She currently continues free
of disease, without further therapy, and maintains a normal and active life.
CONCLUSIONS: This case shows that patients with uterine carcinosarcoma and
positive hormone receptors may benefit from aromatase inhibitor therapy. A
multidisciplinary strategy that includes local therapies such as radiation and/or
surgery should be considered the mainstay of treatment. Systemic therapies such
as hormone inhibitors should be taken into consideration and deserve further
clinical research in the era of precision medicine.
PMID- 28424086
TI - Questioning the application of risk of bias tools in appraising evidence from
natural experimental studies: critical reflections on Benton et al., IJBNPA 2016.
AB - We recently read the article by Benton et al. which reviewed risk of bias in
natural experimental studies investigating the impact of the built environment on
physical activity (Benton et al., 2016; Int J Behav Nutr Phys Act 13:107). As a
technical exercise in assessing risk of bias to understand study quality, we
found the results of this study both interesting and potentially useful. However,
it prompted a number of concerns with the use of risk of bias tools for assessing
the quality of evidence from studies exploiting natural experiments. As we
discuss in this commentary, the rigid application of such tools could have
adverse effects on the uptake and use of natural experiments in population health
research and practice.
PMID- 28424085
TI - The within-host population dynamics of Mycobacterium tuberculosis vary with
treatment efficacy.
AB - BACKGROUND: Combination therapy is one of the most effective tools for limiting
the emergence of drug resistance in pathogens. Despite the widespread adoption of
combination therapy across diseases, drug resistance rates continue to rise,
leading to failing treatment regimens. The mechanisms underlying treatment
failure are well studied, but the processes governing successful combination
therapy are poorly understood. We address this question by studying the
population dynamics of Mycobacterium tuberculosis within tuberculosis patients
undergoing treatment with different combinations of antibiotics. RESULTS: By
combining very deep whole genome sequencing (~1000-fold genome-wide coverage)
with sequential sputum sampling, we were able to detect transient genetic
diversity driven by the apparently continuous turnover of minor alleles, which
could serve as the source of drug-resistant bacteria. However, we report that
treatment efficacy has a clear impact on the population dynamics: sufficient drug
pressure bears a clear signature of purifying selection leading to apparent
genetic stability. In contrast, M. tuberculosis populations subject to less drug
pressure show markedly different dynamics, including cases of acquisition of
additional drug resistance. CONCLUSIONS: Our findings show that for a pathogen
like M. tuberculosis, which is well adapted to the human host, purifying
selection constrains the evolutionary trajectory to resistance in effectively
treated individuals. Nonetheless, we also report a continuous turnover of minor
variants, which could give rise to the emergence of drug resistance in cases of
drug pressure weakening. Monitoring bacterial population dynamics could therefore
provide an informative metric for assessing the efficacy of novel drug
combinations.
PMID- 28424087
TI - Heroes of peer review: Robert Lowe.
AB - In the second of our series of articles celebrating peer reviewers, we talk to
Robert Lowe, who is a Lecturer in computational biology at Queen Mary University
of London, UK, and a valued reviewer for Genome Biology.
PMID- 28424088
TI - Research Exploring Physical Activity in Care Homes (REACH): study protocol for a
randomised controlled trial.
AB - BACKGROUND: As life expectancy increases and the number of older people,
particularly those aged 85 years and over, expands there is an increase in demand
for long-term care. A large proportion of people in a care home setting spend
most of their time sedentary, and this is one of the leading preventable causes
of death. Encouraging residents to engage in more physical activity could deliver
benefits in terms of physical and psychological health, and quality of life. This
study is the final stage of a programme of research to develop and preliminarily
test an evidence-based intervention designed to enhance opportunities for
movement amongst care home residents, thereby increasing levels of physical
activity. METHODS/DESIGN: This is a cluster randomised feasibility trial, aiming
to recruit at least 8-12 residents at each of 12 residential care homes across
Yorkshire, UK. Care homes will be randomly allocated on a 1:1 basis to receive
either the intervention alongside usual care, or to continue to provide usual
care alone. Assessment will be undertaken with participating residents at
baseline (prior to care home randomisation) and at 3, 6, and 9 months post
randomisation. Data relating to changes in physical activity, physical function,
level of cognitive impairment, mood, perceived health and wellbeing, and quality
of life will be collected. Data at the level of the home will also be collected
and will include staff experience of care, and changes in the numbers and types
of adverse events residents experience (for example, hospital admissions, falls).
Details of National Health Service (NHS) usage will be collected to inform the
economic analysis. An embedded process evaluation will obtain information to test
out the theory of change underpinning the intervention and its acceptability to
staff and residents. DISCUSSION: This feasibility trial with embedded process
evaluation and collection of health economic data will allow us to undertake
detailed feasibility work to inform a future large-scale trial. It will provide
valuable information to inform research procedures in this important but
challenging area. TRIAL REGISTRATION: ISRCTN registry, ISRCTN16076575 .
Registered on 25 June 2015.
PMID- 28424089
TI - Feasibility of uterine preservation in the management of early-stage uterine
adenosarcomas: a single institute experience.
AB - BACKGROUND: We aimed to evaluate the efficacy and the safety of uterine
preservation in patients with early-stage uterine adenosarcoma who want to
preserve future fertility. METHODS: We performed a retrospective review of
patients with stage I uterine adenosarcoma diagnosed and treated at a single
institute from 1998 through 2014. RESULTS: Among the total of 31 patients,
uterine preservation surgery was performed in 7 of the nulliparas. Of the 7
patients receiving uterine preservation surgery, 3 showed no evidence of disease
(NED), 2 had persistent disease confined to the uterus, and 2 were alive with
disease (AWD) after recurrence. One patient with an NED status had a vaginal
delivery at term. In the uterine preservation group, 1 patient had sarcomatous
overgrowth at the time of diagnosis and experienced disease recurrence. In the
hysterectomy group, 3 of 24 patients had tumor recurrence. Of the five patients
with tumor recurrence, four (80%) had sarcomatous overgrowth at diagnosis and it
was significantly associated with recurrence by univariate analysis (OR 13.3, p =
0.027). CONCLUSIONS: Uterine preservation represents a possible treatment option
for young female patients who want to maintain fertility. However, a detailed
explanation of the risk of recurrence is necessary, especially in patients with
sarcomatous overgrowth, which seems to be associated with a higher risk of
recurrence. TRIAL REGISTRATION: Retrospectively registered.
PMID- 28424090
TI - Targeted endomyocardial biopsy guided by real-time cardiovascular magnetic
resonance.
AB - BACKGROUND: Endomyocardial biopsies (EMB) are an important diagnostic tool for
myocarditis and other infiltrative cardiac diseases. Routinely, biopsies are
obtained under fluoroscopic guidance with a substantial radiation burden. Despite
procedural success, there is a large sampling error caused by missing the
affected myocardium. Therefore, multiple (>6) biopsies are taken in the clinical
setting. In cardiovascular magnetic resonance (CMR), late gadolinium enhancement
(LGE) depicts areas of affected myocardium in myocarditis or in other
infiltrative cardiomyopathies. Thus, targeted biopsy under real-time CMR image
guidance might reduce the problem of sampling error. METHODS: Seven minipigs of
the Goettingen strain underwent radiofrequency ablation in the left ventricle. At
least two focal lesions were induced on the lateral wall in five and the apex in
two animals. Each ablation lesion was created by two consecutive 30 sec ablations
(max. 30 W, temperature 60-64 degrees C). Biopsies were taken immediately after
lesion induction using a commercially available 7 F conventional bioptome under
fluoroscopic guidance at the ablation site. Afterwards the animals underwent CMR
and lesion visualization by LGE at 3T. The lesions were then targeted and
biopsied under CMR-guidance using a MR-conditional bioptome guided by a steerable
catheter. Interactive real-time (RT) visualization of the intervention on an in
room monitor was based on radial FLASH with nonlinear inverse reconstruction
(NLINV) at a temporal resolution of 42 ms. All samples underwent a standard
histological evaluation. RESULTS: Radiofrequency ablation was successful in all
animals. Fluoroscopy-guided biopsies were performed with a success rate of 6/6
minipigs - resulting in a nonlethal pericardial effusion in one animal.
Visualization of radiofrequency lesions by CMR was successful in 7/7 minipig,
i.e. at least one lesion was clearly visible. Localization and tracking of the
catheters and the bioptome using interactive control of the imaging plane was
achieved in 6/6 MP; however in the animal with a large pericardial effusion after
EMB under fluoroscopy no further EMB was attempted for safety reasons. Biopsies
under interactive RT-CMR guidance were successfully performed in 5/6 animals, in
one animal the bioptome reached the lesion, however the forceps did not cut out a
sample. Specimens obtained under CMR guidance contained part of the lesion in
6/15 (40%) myocardial specimens and in 4/5 (80%) animals in which samples were
achieved. Conventional biopsies revealed ablation lesions in 4/17 (23.5%)
specimens in 3/6 minipigs (50%). CONCLUSION: Focal lesions induced by
radiofrequency ablation in a minipig model are a useful tool for CMR-guided
biopsy studies. In contrast to fluoroscopy, CMR provides excellent visualization
of lesions. Interactive real-time CMR allows excellent passive tracking of the
instruments and EMB provides significantly superior sampling accuracy compared to
fluoroscopy-guided biopsies. Nonetheless, further improvements of MR-compatible
bioptomes and guiding catheters are essential before applying this method in a
clinical setting.
PMID- 28424091
TI - Investigations into the association between soil-transmitted helminth infections,
haemoglobin and child development indices in Manufahi District, Timor-Leste.
AB - BACKGROUND: Timor-Leste has a high prevalence of soil-transmitted helminth (STH)
infections. High proportions of the population have been reported as being
anaemic, and extremely high proportions of children as stunted or wasted. There
have been no published analyses of the contributions of STH to these morbidity
outcomes in Timor-Leste. METHODS: Using baseline cross-sectional data from 24
communities (18 communities enrolled in a cluster randomised controlled trial,
and identically-collected data from six additional communities), analyses of the
association between STH infections and community haemoglobin and child
development indices were undertaken. Stool samples were assessed for STH using
qPCR and participant haemoglobin, heights and weights were measured.
Questionnaires were administered to collect demographic and socioeconomic data.
Intensity of infection was categorised using correlational analysis between qPCR
quantification cycle values and eggs per gram of faeces equivalents, with
algorithms generated from seeding experiments. Mixed-effects logistic and
multinomial regression were used to assess the association between STH infection
intensity classes and anaemia, and child stunting, wasting and underweight.
RESULTS: Very high stunting (60%), underweight (60%), and wasting (20%) in
children, but low anaemia prevalence (15%), were found in the study communities.
STH were not significantly associated with morbidity outcomes. Male children and
those in the poorest socioeconomic quintile were significantly more likely to be
moderately and severely stunted. Male children were significantly more likely
than female children to be severely underweight. Increasing age was also a risk
factor for being underweight. Few risk factors emerged for wasting in these
analyses. CONCLUSIONS: According to World Health Organization international
reference standards, levels of child morbidity in this population constitute a
public health emergency, although the international reference standards need to
be critically evaluated for their applicability in Timor-Leste. Strategies to
improve child development and morbidity outcomes, for example via nutrition and
iron supplementation programmes, are recommended for these communities. Despite
the apparent lack of an association from STH in driving anaemia, stunting,
wasting and underweight, high endemicity suggests a need for STH control
strategies. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Registry ACTRN12614000680662 ; retrospectively registered.
PMID- 28424092
TI - Analyzing the association between fish consumption and osteoporosis in a sample
of Chinese men.
AB - BACKGROUND: The main purpose of this study was to estimate the associations
between frequency of fish food consumption and osteoporosis (OP) in general
Chinese men. METHODS: We conducted a large-scale, community-based, cross
sectional study to investigate the associations by using self-report
questionnaire to access frequency of fish food intake. A total of 1092 men were
available for data analysis in this study. Multiple regression models controlling
for confounding factors to include frequency of fish food consumption variable
were performed to investigate the relationships for OP. RESULTS: Positive
correlations between frequency of fish food consumption and T score were reported
(beta = 0.084, P value = 0.025). Multiple regression analysis indicated that the
frequency of fish food consumption was significantly associated with OP (P < 0.05
for model 1 and model 2). The men with high frequency of fish food consumption
had a lower prevalence of OP. CONCLUSIONS: The findings indicated that frequency
of fish food consumption was independently and significantly associated with OP.
The prevalence of OP was less frequent in Chinese men preferring fish food
habits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02451397
retrospectively registered 28 May 2015.
PMID- 28424093
TI - A survey of national and multi-national registries and cohort studies in juvenile
idiopathic arthritis: challenges and opportunities.
AB - BACKGROUND: To characterize the existing national and multi-national registries
and cohort studies in juvenile idiopathic arthritis (JIA) and identify
differences as well as areas of potential future collaboration. METHODS: We
surveyed investigators from North America, Europe, and Australia about existing
JIA cohort studies and registries. We excluded cross-sectional studies. We
captured information about study design, duration, location, inclusion criteria,
data elements and collection methods. RESULTS: We received survey results from 18
studies, including 11 national and 7 multi-national studies representing 37
countries in total. Study designs included inception cohorts, prevalent disease
cohorts, and new treatment cohorts (several of which contribute to
pharmacosurveillance activities). Despite numerous differences, the data elements
collected across the studies was quite similar, with most studies collecting at
least 5 of the 6 American College of Rheumatology core set variables and the data
needed to calculate the 3-variable clinical juvenile disease activity score. Most
studies were collecting medication initiation and discontinuation dates and were
attempting to capture serious adverse events. CONCLUSION: There is a wide-range
of large, ongoing JIA registries and cohort studies around the world. Our survey
results indicate significant potential for future collaborative work using data
from different studies and both combined and comparative analyses.
PMID- 28424094
TI - Electrical control of calcium oscillations in mesenchymal stem cells using
microsecond pulsed electric fields.
AB - BACKGROUND: Human mesenchymal stem cells are promising tools for regenerative
medicine due to their ability to differentiate into many cellular types such as
osteocytes, chondrocytes and adipocytes amongst many other cell types. These
cells present spontaneous calcium oscillations implicating calcium channels and
pumps of the plasma membrane and the endoplasmic reticulum. These oscillations
regulate many basic functions in the cell such as proliferation and
differentiation. Therefore, the possibility to mimic or regulate these
oscillations might be useful to regulate mesenchymal stem cells biological
functions. METHODS: One or several electric pulses of 100 MUs were used to induce
Ca2+ spikes caused by the penetration of Ca2+ from the extracellular medium,
through the transiently electropermeabilized plasma membrane, in human adipose
mesenchymal stem cells from several donors. Attached cells were preloaded with
Fluo-4 AM and exposed to the electric pulse(s) under the fluorescence microscope.
Viability was also checked. RESULTS: According to the pulse(s) electric field
amplitude, it is possible to generate a supplementary calcium spike with
properties close to those of calcium spontaneous oscillations, or, on the
contrary, to inhibit the spontaneous calcium oscillations for a very long time
compared to the pulse duration. Through that inhibition of the oscillations, Ca2+
oscillations of desired amplitude and frequency could then be imposed on the
cells using subsequent electric pulses. None of the pulses used here, even those
with the highest amplitude, caused a loss of cell viability. CONCLUSIONS: An easy
way to control Ca2+ oscillations in mesenchymal stem cells, through their
cancellation or the addition of supplementary Ca2+ spikes, is reported here.
Indeed, the direct link between the microsecond electric pulse(s) delivery and
the occurrence/cancellation of cytosolic Ca2+ spikes allowed us to mimic and
regulate the Ca2+ oscillations in these cells. Since microsecond electric pulse
delivery constitutes a simple technology available in many laboratories, this new
tool might be useful to further investigate the role of Ca2+ in human mesenchymal
stem cells biological processes such as proliferation and differentiation.
PMID- 28424095
TI - Safety and effectiveness of oral propranolol for infantile hemangiomas started
before 5 weeks and after 5 months of age: an Italian multicenter experience.
AB - BACKGROUND: Despite not being licensed for the treatment of infantile hemangiomas
(IH) in infants younger than 5 weeks or older than 5 months, propranolol is often
used in these age groups to prevent or to treat potentially severe complications.
The objective of the present study was to review the experience of 8 Italian
pediatric and dermatologic centers regarding propranolol treatment for IH started
before 5 weeks or after 5 months of age. METHODS: We retrospectively reviewed the
records of patients followed up for IH, on propranolol treatment started before 5
weeks or after 5 months of age, and collected information on sociodemographic
data, treatment indications, IH involution, IH relapse, and treatment side
effects. RESULTS: A total of 343 patients were enrolled; 15 were started on
propranolol before 5 weeks (group 1), 328 were started after 5 months of age
(group 2). The most frequent indications were permanent aesthetical disfigurement
(91.8%) and function threatening complications (42.6%). In most cases, the
treatment was effective. The involution was partial in 67.7% of patients. In
11.8% of cases a relapse was observed. No relapse was observed in group 1.
Treatment complications were reported in 15.8% of children, most frequently sleep
disorders (6.6%), followed by irritability (5.1%) and diarrhea (2.2%). Only a
case of mild constipation was observed in group 1. CONCLUSION: The safety and
effectiveness profile of propranolol in infants younger than 5 weeks or older
than 5 months may be acceptable. Taking in account propranolol's potential in
preventing severe complications, further studies should assess the acceptability
of propranolol treatment, especially in the <5-week age group .
PMID- 28424096
TI - Metabolic and proteomic analyses of product selectivity and redox regulation in
Clostridium pasteurianum grown on glycerol under varied iron availability.
AB - BACKGROUND: Clostridium pasteurianum as an emerging new microbial cell factory
can produce both n-butanol (BuOH) and 1,3-propanediol (1,3-PDO), and the pattern
of product formation changes significantly with the composition of the culture
medium. Among others iron content in the medium was shown to strongly affect the
products selectivity. However, the mechanism behind this metabolic regulation is
still unclear. For a better understanding of such metabolic regulation and for
process optimization, we carried out fermentation experiments under either iron
excess or iron limitation conditions, and performed metabolic, stoichiometric and
proteomic analyses. RESULTS: 1,3-PDO is most effectively produced under iron
limited condition (Fe-), whereas 1,3-PDO and BuOH were both produced under iron
rich condition (Fe+). With increased iron availability the BuOH/1,3-PDO ratio
increased significantly from 0.27 mol/mol (at Fe-) to 1.4 mol/mol (at Fe+).
Additionally, hydrogen production was enhanced significantly under Fe+ condition.
Proteomic analysis revealed differentiated expression of many proteins including
several ones of the central carbon metabolic pathway. Among others, pyruvate:
ferredoxin oxidoreductase, hydrogenases, and several electron transfer
flavoproteins was found to be strongly up-regulated under Fe+ condition, pointing
to their strong involvement in the regeneration of the oxidized form of
ferredoxin, and consequently their influences on the product selectivity in C.
pasteurianum. Of particular significance is the finding that H2 formation in C.
pasteurianum is coupled to the ferredoxin-dependent butyryl-CoA dehydrogenase
catalyzed reaction, which significantly affects the redox balance and thus the
product selectivity. CONCLUSIONS: The metabolic, stoichiometric and proteomic
results clearly show the key roles of hydrogenases and ferredoxins dependent
reactions in determining the internal redox balance and hence product
selectivity. Not only the NADH pool but also the regulation of the ferredoxin
pool could explain such product variation under different iron conditions.
PMID- 28424097
TI - Unusual course of generalized lymph node primary plasmacytoma in a patient with
Sjogren's syndrome: a case report.
AB - BACKGROUND: Primary lymph node plasmacytoma is a rare disease that typically
involves lymph nodes of the neck. In only 15% of cases is the disease
generalized. Here, we present a case of generalized lymph node plasmacytoma in a
patient with Sjogren's syndrome with an unusual course. CASE PRESENTATION: A 48
year-old white woman presented to our hospital with enlargement of groups of
lymph nodes, liver, and spleen. Her medical history was consistent with a 12-year
course of Sjogren's syndrome. Blood and urine immunochemistry showed a massive
(72 g/l) M-gradient formed from immunoglobulin Akappa in the serum and monoclonal
free kappa-type light chains in her urine. A skeletal X-ray revealed no bone
destruction. Cytological and histological bone marrow assays showed no signs of
plasma cell infiltration. The microarchitecture of her neck and inguinal lymph
nodes was destroyed. Only small remnants of B cell follicles were found, while
the interfollicular areas were expanded and infiltrated by CD138, MuM1, CD43, and
IgAkappa-positive plasma cells. After nine cycles of doxorubicin,
cyclophosphamide, vincristine, and prednisolone chemotherapy, complete remission
was achieved. However, the lymphoma relapsed 3 months later, with histological
verification in her femoral lymph node. Despite the absence of subsequent
adequate therapy, she gradually achieved complete remission of plasmacytoma with
the disappearance of paraproteins. CONCLUSIONS: Currently, primary lymph node
plasmacytoma is generally considered a nodal marginal zone lymphoma with an
extensive plasmacytic differentiation. In our case, despite the critical
histological and immunohistochemical evaluation of three lymph node biopsies from
different anatomical areas at different times, no signs of nodal marginal zone
lymphoma were found. An 18-year follow-up of our patient with primary lymph node
plasmacytoma demonstrated an extremely unusual clinical course. Initially,
primary lymph node plasmacytoma was refractory to chemotherapy. However,
subsequently, she underwent a complete spontaneous remission of plasmacytoma.
PMID- 28424098
TI - Identification of odorant-binding protein genes in Galeruca daurica (Coleoptera:
Chrysomelidae) and analysis of their expression profiles.
AB - Odorant-binding proteins (OBPs) play a fundamental role in insect olfaction. In
recent years, Galeruca daurica (Joannis) (Coleoptera: Chrysomelidae) has become
one of the most important insect pests in the Inner Mongolian grasslands of
China. This pest only feeds on the species of Allium plants, implying the central
role of olfaction in its search for specific host plants. However, the olfaction
related proteins have not been investigated in this beetle. In this study, we
identified 29 putative OBP genes, namely GdauOBP1-29, from the transcriptome
database of G. daurica assembled in our laboratory by using RNA-Seq. All 29 genes
had the full-length open reading frames except GdauOBP29, encoding proteins in
length from 119 to 202 amino acids with their predicted molecular weights from 12
to 22 kDa with isoelectric points from 3.88 to 8.84. Predicted signal peptides
consisting of 15-22 amino acid residues were found in all except GdauOBP6,
GdauOBP13 and GdauOBP29. The amino acid sequence identity between the 29 OBPs
ranged 8.33-71.83%. GdauOBP1-12 belongs to the Classic OBPs, while the others
belong with the Minus-C OBPs. Phylogenetic analysis indicated that GdauOBPs are
the closest to CbowOBPs from Colaphellus bowringi. RT-PCR and qRT-PCR analyses
showed that all GdauOBPs were expressed in adult antennae, 11 of which with
significant differences in their expression levels between males and females.
Most GdauOBPs were also expressed in adult heads (without antennae), thoraxes,
abdomens, legs and wings. Moreover, the expression levels of the GdauOBPs varied
during the different development stages of G. daurica with most GdauOBPs
expressed highly in the adult antennae but scarcely in eggs and pupae. These
results provide insights for further research on the molecular mechanisms of
chemical communications in G. daurica.
PMID- 28424099
TI - Influence of opacification in the frontal recess on frontal sinusitis.
AB - OBJECTIVES: This study aimed to radiologically evaluate the influence of
inflammatory changes in frontal recess cells on frontal sinusitis. METHODS: A
total of 93 patients (186 sides) who underwent primary sinonasal surgery at Hyogo
College of Medicine were enrolled in 2015 and 2016. Opacification of agger nasi,
fronto-ethmoidal, ethmoid bulla, suprabullar and frontal bulla cells was
determined by pre-operative computed tomography and its influence on frontal
sinusitis was investigated. RESULTS: In all, 42 per cent of 186 sides were
affected by frontal sinusitis. Agger nasi, ethmoid bulla, fronto-ethmoidal,
suprabullar and frontal bulla cells were identified in 99 per cent, 100 per cent,
38 per cent, 69 per cent, and 16 per cent of sides, respectively. The presence of
frontal recess cells and frontal ostium size did not significantly influence
frontal sinusitis development. However, opacification of agger nasi, type 1
fronto-ethmoidal and suprabullar cells significantly influenced frontal sinusitis
development. CONCLUSION: Frontal sinusitis is caused by inflammatory changes in
frontal recess cells.
PMID- 28424100
TI - Out-patient flexible carbon dioxide laser surgery for benign laryngopharyngeal
pathologies via transnasal flexible laryngo-oesophagoscopy.
AB - OBJECTIVE: To assess the feasibility and outcomes of flexible carbon dioxide
laser surgery in a clinic-based setting. METHODS: A prospective study was
conducted in a tertiary centre. Clinical indications, clinical outcomes and
patient satisfaction were assessed in patients treated with flexible carbon
dioxide laser surgery via transnasal endoscopy and followed up over a period of
up to nine months. Patients who were not fit for general anaesthesia or those
with lesions that cannot be accessed by micro-laryngoscopy were included.
RESULTS: A total of 13 patients (14 procedures) were included. Clinical
indications for surgery were small-to-medium sized benign pathologies in the
upper aero-digestive tract. Patient satisfaction was assessed using a validated
questionnaire. CONCLUSION: Early data suggest that flexible carbon dioxide laser
is a versatile and feasible instrument with potential applications for a range of
benign pathologies in the upper aero-digestive tract.
PMID- 28424101
TI - Limited impacts of truck-based ultra-low-volume applications of mosquito
adulticides on mortality in honey bees (Apis mellifera).
AB - Adulticides applied against mosquitoes can reduce vector populations during times
of high arbovirus transmission. However, impacts of these insecticides on
pollinators and other non-target organisms are of concern to mosquito control
professionals, beekeepers and others. We evaluated mortality of Culex
quinquefasciatus and Apis mellifera when caged insects were exposed to low and
high label rates of four common adulticides (Aqua-PursuitTM [permethrin], Duet(r)
[prallethrin + sumithrin], Fyfanon(r) [malathion] and Scourge(r) [resmethrin]) at
six distances up to 91.4 m from a truck-mounted ultra-low-volume sprayer. Honey
bee mortality was both absolutely low (61 m had limited impacts on honey bee
mortality while providing effective mosquito control.
PMID- 28424102
TI - Gaining insights into the ecological role of the New Zealand sole (Peltorhamphus
novaezeelandiae) through parasites.
AB - Despite the fact that tapeworms comprise the bulk of parasite communities of
sharks in marine ecosystems, little is known about their life cycles and, more
specifically, about the potential intermediate hosts they utilize as transmission
routes. In the absence of morphological features required for specific
identification of larval tapeworms from potential intermediate hosts, recent
molecular advances have contributed to linking larval and adult parasites and, in
some instances, uncovering unknown trophic links. Host-parasite checklists are
often the first source of information consulted to assess the diversity and host
specificity of parasites, and provide insights into parasite identification.
However, these host-parasite checklists are only useful if they encompass the
full spectrum of associations between hosts and parasites. A checklist of New
Zealand fishes and their parasites has been published, but recent parasitological
examinations of commercial fish species reveal that the checklist appears to be
far from complete. We focused our current study on a comprehensive survey of
macroparasites of a commercial species, the New Zealand sole (Peltorhamphus
novaezeelandiae) off the coast of Otago, New Zealand. Specifically, we were
expecting to recover marine tapeworms using sharks as their definitive hosts that
are generally underreported in parasite surveys. The parasites recovered included
tapeworms, flukes, round worms and thorny-headed worms. Surprisingly, a large
proportion of the non-tapeworm parasites we recovered were not previously
reported from this fish species. A discussion on the potential ecological roles
played by this fish species in the transmission of parasites is included.
PMID- 28424103
TI - Olfactory disturbances in ageing with and without dementia: towards new
diagnostic tools.
AB - BACKGROUND: Olfactory disorders increase with age and often affect elderly people
who have pre-dementia or dementia. Despite the frequent occurrence of olfactory
changes at the early stages of neurodegenerative disorders such as Alzheimer's
disease, olfactory disorders are rarely assessed in daily clinical practice,
mainly due to a lack of standardised assessment tools. The aims of this review
were to (1) summarise the existing literature on olfactory disorders in ageing
populations and patients with neurodegenerative disorders; (2) present the
strengths and weaknesses of current olfactory disorder assessment tools; and (3)
discuss the benefits of developing specific olfactory tests for neurodegenerative
diseases. METHODS: A systematic review was performed of literature published
between 2000 and 2015 addressing olfactory disorders in elderly people with or
without Alzheimer's disease or other related disorders to identify the main tools
currently used for olfactory disorder assessment. RESULTS: Olfactory disorder
assessment is a promising method for improving both the early and differential
diagnosis of Alzheimer's disease. However, the current lack of consensus on which
tests should be used does not permit the consistent integration of olfactory
disorder assessment into clinical settings. CONCLUSION: Otolaryngologists are
encouraged to use olfactory tests in older adults to help predict the development
of neurodegenerative diseases. Olfactory tests should be specifically adapted to
assess olfactory disorders in Alzheimer's disease patients.
PMID- 28424104
TI - Assessing the impact of conversational overlap in content on child language
growth.
AB - When engaged in conversation, both parents and children tend to re-use words that
their partner has just said. This study explored whether proportions of maternal
and/or child utterances that overlapped in content with what their partner had
just said contributed to growth in mean length of utterance (MLU), developmental
sentence score, and vocabulary diversity over time. We analyzed the New England
longitudinal corpus from the CHILDES database, comprising transcripts of mother
child conversations at 14, 20, and 32 months, using the CHIP command to compute
proportions of utterances with overlapping content. Rates of maternal overlap,
but not child overlap, at earlier time-points predicted child language outcomes
at later time-points, after controlling for earlier child MLU. We suggest that
maternal overlap plays a formative role in child language development by
providing content that is immediately relevant to what the child has in mind.
PMID- 28424105
TI - Specific impact of stimulant, alcohol and cannabis use disorders on first-episode
psychosis: 2-year functional and symptomatic outcomes.
AB - BACKGROUND: Many studies have concluded that cannabis use disorder (CUD)
negatively influences outcomes in first-episode psychosis (FEP). However, few
have taken into account the impact of concurrent misuse of other substances.
METHODS: This 2-year, prospective, longitudinal study of FEP patients, aged
between 18 and 30 years, admitted to early intervention programs in Montreal,
Quebec, Canada, examined the specific influence of different substance use
disorders (SUD) (alcohol, cannabis, cocaine, amphetamines) on service
utilization, symptomatic and functional outcomes in FEP. RESULTS: Drugs and
alcohol were associated with lower functioning, but drugs had a greater negative
impact on most measures at 2-year follow-up. Half of CUD patients and more than
65% of cocaine or amphetamine abusers presented polysubstance use disorder (poly
SUD). The only group that deteriorated from years 1 to 2 (symptoms and
functioning) were patients with persistent CUD alone. Outcome was worse in CUD
than in the no-SUD group at 2 years. Cocaine, amphetamines and poly-SUD were
associated with worse symptomatic and functional outcomes from the 1st year of
treatment, persisting over time with higher service utilization
(hospitalization). CONCLUSION: The negative impact attributed to CUD in previous
studies could be partly attributed to methodological flaws, like including
polysubstance abusers among cannabis misusers. However, our investigation
confirmed the negative effect of CUD on outcome. Attention should be paid to
persistent cannabis misusers, since their condition seems to worsen over time,
and to cocaine and amphetamine misusers, in view of their poorer outcome early
during follow-up and high service utilization.
PMID- 28424106
TI - Early developmental influences on self-esteem trajectories from adolescence
through adulthood: Impact of birth weight and motor skills.
AB - While the trajectory of self-esteem from adolescence to adulthood varies from
person to person, little research has examined how differences in early
developmental processes might affect these pathways. This study examined how
early motor skill development interacted with preterm birth status to predict
self-esteem from adolescence through the early 30s. We addressed this using the
oldest known, prospectively followed cohort of extremely low birth weight (<1000
g) survivors (N = 179) and normal birth weight controls (N = 145) in the world,
born between 1977 and 1982. Motor skills were measured using a performance-based
assessment at age 8 and a retrospective self-report, and self-esteem was reported
during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found
that birth weight status moderated the association between early motor skills and
self-esteem. Stable over three decades, the self-esteem of normal birth weight
participants was sensitive to early motor skills such that those with poorer
motor functioning manifested lower self-esteem, while those with better motor
skills manifested higher self-esteem. Conversely, differences in motor skill
development did not affect the self-esteem from adolescence to adulthood in
individuals born at extremely low birth weight. Early motor skill development may
exert differential effects on self-esteem, depending on whether one is born at
term or prematurely.
PMID- 28424108
TI - A systematic review of early modelling studies of Ebola virus disease in West
Africa - CORRIGENDUM.
PMID- 28424109
TI - The Impact of Gender on Complications and Outcomes of Pelvic Fracture.
PMID- 28424107
TI - Early maturation and substance use across adolescence and young adulthood: A
longitudinal study of Finnish twins.
AB - Early maturation, indexed by pubertal development (PD), has been associated with
earlier initiation and greater frequency of adolescent substance use, but this
relationship may be biased by confounding factors and effects that change across
development. Using a population-based Finnish twin sample (N = 3,632
individuals), we conducted twin modeling and multilevel structural equation
modeling of the relationship between PD and substance use at ages 12-22. Shared
environmental factors contributed to early PD and heavier substance use for
females. Biological father absence was associated with early PD for boys but not
girls, and did not account for the relationship between PD and substance use. The
association between early PD and heavier substance use was partially due to
between-family confounds, although early PD appeared to qualitatively alter long
term trajectories for some substances (nicotine), but not others (alcohol).
Mediation by peer and parental factors did not explain this relationship within
families. However, higher peer substance use and lower parental monitoring were
themselves associated with heavier substance use, strengthening the existing
evidence for these factors as targets for prevention/intervention efforts. Early
maturation was not supported as a robust determinant of alcohol use trajectories
in adolescence and young adulthood, but may require longer term follow-up. Subtle
effects of early PD on nicotine and illicit drug use trajectories throughout
adolescence and adulthood merit further investigation.
PMID- 28424110
TI - Native Americans Have an Increased Risk of Major Bile Duct Injury during
Laparoscopic Cholecystectomy: Results from a Statewide Analysis.
PMID- 28424111
TI - Management of Recurrent Invasive Ductal Carcinoma in Transrectus Abdominis
Myocutaneous Flap and Lymphatic Remodeling to the Contralateral Axilla.
PMID- 28424112
TI - Upregulation of CA 19-9 in Complicated Cholecystitis.
PMID- 28424113
TI - Vicarious Contrast Excretion with Prolonged Retention Causing Biliary Colic.
PMID- 28424114
TI - Retroversus Implantation of a Situs Solitus Deceased Donor Liver into a Situs
Inversus Totalis Recipient.
PMID- 28424115
TI - Continuous Abdominal Irrigation for Treatment of Tertiary Peritonitis in the
Immunosuppressed Patient after Solid Organ Transplant: A Novel Approach.
PMID- 28424116
TI - Hyponatremia on Initial Presentation Correlates with Suboptimal Outcomes after
Traumatic Brain Injury.
PMID- 28424117
TI - Damage Control Surgery and the Management of a Cholecystocolic Fistula.
PMID- 28424118
TI - Intussusception in the Adult Population: A Challenge to Surgeons.
PMID- 28424119
TI - The Changing Epidemiology of Diverticulitis in the United States.
PMID- 28424121
TI - Gallbladder Polyps in Children: A Painful Inflammatory Process.
PMID- 28424122
TI - Vascular Complications in Pediatric Port Removal.
PMID- 28424123
TI - A Case of Ingested Dental Prosthesis with Sharp Clasps Successfully Removed
Through Anus Using Part of a Plastic Glove.
PMID- 28424124
TI - Acute Respiratory Distress Syndrome Incidence, But Not Mortality, Has Decreased
Nationwide: A National Trauma Data Bank Study.
AB - Acute respiratory distress syndrome (ARDS) incidence is reported to have
decreased in recent years. However, no large-scale study to date has exclusively
examined ARDS in the critically injured. We sought to examine the national
incidence of ARDS and its associated outcomes exclusively in adult trauma
patients. The National Trauma Data Bank (NTDB) was queried to evaluate the
incidence of ARDS and associated outcomes over a 6-year study period (2007-2012).
Included patients were >=18 years old, with at least one ventilator day, and
complications recorded. ARDS-associated outcomes and complications were also
analyzed. Mean age increased over the study period (48.1-51.4 years, P < 0.003).
ARDS incidence decreased from 21.5 to 8.5 per cent (P < 0.001). Length of stay
(LOS), intensive care unit LOS (ICU LOS), and ventilator days decreased over
time. Mortality increased from 21.3 to 24.9 per cent (P < 0.002). Incidence of
pneumonia and acute kidney injury increased marginally (39.5-40.9% and 11.4
12.3%, respectively). Sepsis trended down from 2007 to 2010, after which
comparable NTDB data were not available. ARDS incidence in mechanically
ventilated adult trauma patients has decreased significantly in recent years. We
theorize this is likely attributable to improved critical care strategies. Unlike
ARDS incidence, mortality in this patient population has not improved despite
these advancements.
PMID- 28424125
TI - Thromboelastography Utilization in Delayed Recurrent Coagulopathy after Severe
Eastern Diamondback Rattlesnake Envenomation.
AB - Venomous snakebites are fairly common in the United States and can present with a
wide range of symptoms. A 48-year-old man presented after Eastern Diamondback
rattlesnake envenomation. His hospital course was complicated by right leg
compartment syndrome and delayed recurrent coagulopathy, requiring multiple doses
of Crotalidae Polyvalent Immune Fab (CroFab) antivenom and transfusions.
Thromboelastography was used as an adjunct to standard coagulation studies in
monitoring his delayed recurrent coagulopathy.
PMID- 28424126
TI - The Novel Use of Resuscitative Endovascular Balloon Occlusion of the Aorta to
Explore a Retroperitoneal Hematoma in a Hemodynamically Unstable Patient.
AB - Balloon occlusion of the aorta was first described by C.W. Hughes in 1954, when
it was used as a tamponade device for three wounded soldiers during the Korean
War suffering from intra-abdominal hemorrhage. Currently, the device is indicated
in trauma patients as a surrogate for resuscitative thoracotomy. Brenner et al.
reported a case series describing the use of resuscitative endovascular balloon
occlusion of the aorta (REBOA) in advanced hemorrhagic shock. Their conclusion
was that "it is a feasible method for proximal aortic control." We describe the
novel use of REBOA before retroperitoneal hematoma exploration in a
hemodynamically unstable patient. Reported is a 19-year-old blunt trauma victim
where REBOA was successfully deployed as a means for proximal arterial control
before a Zone 1 retroperitoneal hematoma exploration. The source of the patient's
hemorrhagic shock was multifactorial: grade V hepatic injury, retrohepatic
inferior vena cava laceration, and right renal vein avulsion with Zone 1
retroperitoneal hematoma. Immediate return of perfusion pressure, as systolic
pressures increased from 50 to 150 mm Hg. Hemodynamic improvements were
accompanied by decreased transfusion and vasopressor requirements. In addition,
the surgeons were able to enter the retroperitoneal hematoma under controlled
conditions. REBOA is an attractive new tool to gain proximal aortic control in
select patients with hemorrhagic shock. It is less morbid, possibly more
efficient, and appears to be more effective than resuscitative thoracotomy. REBOA
is certainly feasible for proximal aortic control before retroperitoneal
exploration, and should be considered in select patients.
PMID- 28424127
TI - Analysis of Mortality in Traumatically Injured Patients Based on Body Mass Index
and Mechanism Reveals Highest Mortality among the Underweight in Comparison with
the Ideal Weight Patients.
AB - The purpose of this study was to evaluate the effect of body mass index (BMI) on
mortality after traumatic injury. The records of patients from 2012 to 2015 were
retrospectively reviewed. The patients were stratified into the following groups
based on admission BMI (kg/m2): underweight (UW) (BMI <19), ideal weight (IW)
(BMI = 19-24.9), overweight (OW) (BMI = 25-29.9), obese (OB) (BMI = 30-39.9), and
morbid obese (MO) (BMI >40). The groups were well matched with no significant
differences in demographics and Injury Severity Score. Morality for the IW group
was compared with the remaining BMI groups. A total of 6049 patients were
identified. In comparison with IW group, the UW mortality was significantly
higher (IW vs UW, 4.1% vs 8.8%, P = 0.001); however, the there was no significant
difference with remaining groups. There was also no significant difference in
mortality between IW and the remaining groups for patients that went directly to
the operating room or for patients that had penetrating trauma (stab wounds and
gunshot wounds). However, for blunt trauma, the mortality was significantly
higher for UW (IW vs UW, 4.3% vs 9.4%, P = 0.001), no different for IW vs OW
(4.3% vs 3.7%, P = 0.3), and significantly lower for IW vs OB (4.3% vs 2.8%, P =
0.04) and for IW vs MO (4.3% vs 1.0%, P = 0.03). After traumatic injuries, it is
the underweight patients (BMI <19) and not the obese, that are at a significantly
higher risk for overall mortality; this difference is especially evident after
blunt trauma where obesity may actually confer a protective role.
PMID- 28424128
TI - Analysis of All-Terrain Vehicle Trauma Data: Implications for Increased
Regulation and Injury Prevention.
AB - To determine the incidence and severity of all-terrain vehicle crashes (ATVCs)
compared with motorcycle crashes (MCCs) in all critically injured patients.
Prospective data were retrospectively reviewed on 1840 patients involved in ATVCs
and MCCs admitted to a rural level one trauma center over 16 years. ATVC patients
(n = 655) were younger (25 vs 38, P < 0.0001), more likely female (20% vs 11%, P
< 0.001), less severely injured (13.5 vs 16, P < 0.0001), had similar Glasgow
Coma Score (13.3 vs 13.4, p = NS), less helmet use (6% vs 69%, P < 0.0001), more
closed head injuries (59.7% vs 54.3%, P < 0.05), more facial injuries (16.9%vs
12.5%, P < 0.05), and lower mortality rate (2.8% vs 5.9%, P < 0.01) compared with
MCC patients (n = 1172). Pediatric patients involved in ATVC were more common
(29.8% vs 4.8%, P < 0.001), had decreased helmet use (12% vs 59%, P < 0.001) and
decreased mortality (3.5% vs 14.3%, P < 0.01). Further injury prevention efforts
regarding helmet use and increased regulations regarding ATVCs are needed to
decrease the morbidity associated with these recreational vehicles.
PMID- 28424129
TI - Hospital Characteristics Affect Consent and Conversion Rates for Potential Organ
Donors.
AB - Consent and conversion rates of potential organ donors in the United States need
to be maximized to match the number of individuals awaiting organ donation.
Studies to date have not focused on characteristics of centers with better
outcomes. We performed an 8-year (2006-2014) retrospective study of our local
organ procurement organization database. We categorized hospitals in our region
as academic centers versus nonacademic centers, trauma centers versus nontrauma
centers, and large (>=400 beds) centers versus small (<400 beds) centers. We also
compared trauma centers with Level I designation to all other centers. Primary
outcomes included consent and conversion rates for potential organ donors. There
were 22,732 referrals to our organ procurement organization that resulted in
1,057 eligible deaths. When comparing academic to nonacademic hospitals, academic
hospitals had higher consent (71% vs 59%, P < 0.0001) and conversion (73% vs 64%,
P = 0.008) rates. Level I trauma centers had better consent and conversion rates
when compared to all other hospitals, 73 versus 55 per cent and 76 versus 61 per
cent respectively, P < 0.0001 for both. The small, academic, trauma centers had
the highest consent and conversion rates, 77 and 78 per cent, respectively, P <
0.0001 for both. Hospital characteristics such as academic involvement, Level I
trauma designation, and size impact consent and conversion rates for potential
organ donors. Small (<400 bed), academic, trauma centers have the highest consent
rates and conversion rates. Factors for success in these institutions should be
examined and applied to assist in improving donor rates across all types of
hospitals.
PMID- 28424130
TI - Invasive Pleomorphic Lobular Histology Is an Adverse Prognostic Factor on
Survival in Patients with Breast Cancer.
AB - Invasive pleomorphic lobular carcinoma (IPLC) is defined to be an uncommon and
different subtype of classical invasive lobular carcinoma (ILC). This special
variant is characterized by significant cytological atypia and pleomorphism which
differs from the cytological uniformity of ILC. IPLC has been shown to have some
poor prognostic factors such as axillary node metastasis and higher histological
grade which may lead to poor clinical courses including a short relapse time,
increased risk of recurrence and a decreased survival. The aim of this study is
to investigate the clinicopathological characteristics and prognosis of IPLC in
comparison with ILC and also to evaluate if IPLC is a different clinical entity
compared to ILC. A total number of 4418 breast cancer patients treated between
1996 and 2015 in Hacettepe University Cancer Institute, were retrospectively
analyzed. Among 4418 patients, 210 were diagnosed with ILC and 23 patients
diagnosed with pure IPLC. In this present study, clinicopathological
characteristics, disease free survival (DFS) and overall survival (OS) of
patients with ILC and IPLC were compared. This study design is one of the rare
face to face comparison of pure IPLC and ILC. Patients with IPLC had an increased
rate of higher histologic grade, extracapsular extension, lymphovascular invasion
and lower percentage of hormone positivity than those of patients with ILC.
During the follow-up time, IPLC group experienced 4 cases (17.3%) of recurrence,
5 cases (21.7%) of death and 2 cases (8.7%) of progression in 3 metastatic
patients compared to that of 27 cases (12.9%) of recurrence, 29 cases (13,8%) of
death and 14 cases (6.7%) of progression in 19 metastatic patients in the ILC
group. Patients with IPLC had a worse DFS and OS duration than patients with ILC
(P = 0.02 for OS, P = 0.04 for DFS). In conclusion, IPLC is a different and a
special breast cancer subtype. This study suggests that IPLC is a distinct
clinical entity with an advanced stage and more aggressive clinical course.
Patients with IPLC reveal poorer prognostic factors such as higher histological
grade, relative lower percentages of hormone positivity, and increased rate of
recurrences resulting in poor clinical outcomes and worse survival. Nowadays, it
is observed that current treatment methods for IPLC do not seem as successful as
in ILC and failed to be effective. Thence, individual therapies including more
aggressive surgery and adjuvant or neoadjuvant chemotherapy even in the earlier
stages of breast cancer should be performed for this distinct variant.
PMID- 28424131
TI - Postoperative Complications Predict 30-Day Readmission in Geriatric General
Surgery Patients.
AB - The Affordable Care Act has placed unplanned patient readmissions under more
scrutiny than ever. Geriatric patients, in particular, suffer a disproportionate
amount of complications from any kind of hospitalization, including readmissions.
This study seeks to identify risk factors in this population that predispose them
to an unplanned readmission within 30 days after index surgery. The National
Surgical Quality Improvement Program database was used to select patients 65
years and older, who underwent general surgery procedures in 2012. Patient
demographics, comorbidities, complications, and readmissions were analyzed. A Cox
regression survivorship model was used for multivariate analysis. A total of 7712
patients were reviewed; 617 patients (8.0%) had an unplanned readmission within
30 days of their operation. Cox regression revealed five different independent
predictors of unplanned readmission within 30 days. They are age [P = 0.009,
hazard ratio (HR) = 1.016, 95% confidence interval (CI) = 1.01-1.03], American
Society of Anesthesiologists Class >2 (P = 0.037, HR = 1.22, CI = 1.024-1.475),
operation time (minutes) (P = 0.001, HR = 1.001, CI = 1.00-1.002), any
complication (P = 0.03, HR = 1.449, CI = 1.33-1.852), and deep vein thrombosis (P
= 0.03, HR = 1.87, CI = 1.31-3.85). Using Cox regression to adjust for patient
length of stay, age, American Society of Anesthesiologists class, any
complication, operation time, and venous thromboembolism all independently
increased the rate of unplanned readmissions. Patients who suffer any
complication or a venous thromboembolism postoperatively are at a particularly
high risk of readmission. These patients should be targeted for increased
inpatient monitoring and included in preventable readmission programs after
discharge.
PMID- 28424132
TI - Outcomes of Recreational Activity-Associated Trauma in Elderly Persons on Blood
Thinning Medications.
AB - With increasing life expectancy, the elderly are participating in recreational
activities traditionally pursued by younger persons. Elderly patients have many
reasons for worse outcomes after trauma, one of which may be the rising use of
anticoagulant and/or antiplatelet medications. This study aimed to determine
whether preinjury use of these agents yielded worse outcomes in geriatric
patients injured during high-impact recreational activities. The National Trauma
Data Bank was reviewed from 2007 to 2010 for patients >=65 years admitted to
Level I or II trauma centers with ICD-9 E-codes for specific mechanisms of
injury. These included motorcycles, bicycles, snowmobiles, all-terrain vehicles,
equestrian, water and alpine skiing, snowboarding, and others. Patients with
preinjury bleeding disorder (BD), including warfarin and clopidogrel use, were
compared with controls via a coarsened exact matching analysis. BD patients (294)
were compared with 3929 controls. Although increased in BD patients, no
significant mortality differences were observed in unmatched or matched analyses.
BD patients yielded greater hospital length of stay (5 vs 4 days, P = 0.020) with
increased odds of receiving five units or more of blood (7.0% vs 2.1%, odds ratio
= 4.7, P < 0.001) and of deep vein thrombosis (7.6% vs 3.8%, odds ratio = 2.1, P
= 0.018). Elderly patients with BD, including warfarin or clopidogrel use, do not
seem to have significantly increased mortality after injury during specified
recreational activities. BD patients had greater hospital length of stay,
transfusion requirements, and deep vein thrombosis rates. These findings may
inform counseling for those taking such medications as to the potential for
adverse outcomes.
PMID- 28424133
TI - Carotid Duplex Ultrasonography: Additional Imaging Is Rarely Necessary for
Appropriate Treatment Planning for Carotid Artery Disease.
AB - This study was conducted to determine the utility of multiple imaging studies (CT
angiography, magnetic resonance angiography, and/or conventional angiography), in
addition to duplex ultrasonography (DU), in evaluating patients with carotid
stenosis. A retrospective case series was conducted of patients with carotid
stenosis who underwent DU alone or DU plus additional imaging. Concordance
between DU and additional imaging and the effect on treatment plan was evaluated.
Two hundred patients with carotid stenosis were evaluated. Sixty-four had DU plus
additional imaging. Sixty-two of the patients (96.9%) had no change in treatment
due to additional imaging. Only 2 of the 64 patients (3.1%) with additional
imaging had a change in treatment plan. In conclusion, additional imaging, beyond
DU, is rarely necessary for treatment planning in patients with carotid disease.
PMID- 28424134
TI - Six-Year Experience of Outpatient Total and Completion Thyroidectomy at a Single
Academic Institution.
AB - Outpatient thyroidectomy has become slowly accepted with various published
reports predominantly examining partial or subtotal thyroidectomy. Concerns
regarding the safety of outpatient total and completion thyroidectomy remain,
especially with regard to vocal fold paralysis, hypocalcemia, and catastrophic
hematoma. We aimed to evaluate the safety of outpatient thyroid surgery in a
large cohort by retrospectively comparing outcomes in those who underwent
outpatient (n = 251) versus inpatient (n = 291) completion or total thyroidectomy
between February 2009 and February 2015. Outpatient completion and total
thyroidectomy had lower rates of temporary hypocalcemia (6% vs 24.4%; P < 0.001)
and no significant difference in rates of return to emergency department (1.2% vs
1.4%), hematoma formation (0.8% vs 0.7%), temporary (2% vs 4.1%) or permanent
(0.4% vs 0.7%) vocal fold paralysis, or permanent hypocalcemia (0.4% vs 0%)
compared with the inpatient group. Outpatients requiring calcium replacement had
shorter duration of postoperative calcium supplementation (44.4 +/- 59.3 days vs
63.3 +/- 94.4 days; P < 0.001). Our data demonstrate similar safety in outpatient
and inpatient total and completion thyroidectomy.
PMID- 28424135
TI - Bladder Fill after Laparoscopic Inguinal Hernia Repair Reduces Time to Discharge.
AB - Laparoscopic inguinal herniorrhaphy (LIH) has a relatively high risk of urinary
retention. Bladder dysfunction may delay discharge after LIH. We hypothesized
that filling the bladder before Foley catheter removal decreases time to
discharge (TTD) after LIH. A secondary aim was to determine incidence of
postoperative urinary retention (POUR) after bladder fill (BF). We reviewed a
consecutive series of total extraperitoneal and transabdominal preperitoneal LIH
procedures performed by a single surgeon at our institution from 2010 to 2013.
All patients were catheterized during LIH, and selected patients received a 200
mL saline BF before Foley catheter removal. Patients were required to void >250
mL before discharge. TTD and incidence of POUR were compared between the BF and
no-BF groups. A total of 161 LIH cases were reviewed. BF was performed in 89/161
(55%) of cases. TTD was significantly shorter in the BF versus the no-BF group
(222 vs 286 minutes, respectively; P < 0.01). Patient and operative
characteristics were similar between the BF and no-BF groups (P > 0.05).
Incidence of POUR in the BF and the no-BF group was 10.1 and 16.7 per cent,
respectively; however, this difference was not significant (P = 0.22). No
postoperative urinary tract infection occurred in either group. In conclusions,
postoperative BF significantly reduces TTD after LIH. Further studies may help to
determine whether shorter postanesthesia care unit time and lower POUR rates
associated with BF can lower LIH procedural costs and increase patient
satisfaction.
PMID- 28424136
TI - The Role of Doctors and Patients in Appendicitis Perforation.
AB - In this study, we aimed to determine factors that cause appendix perforations and
to identify the role of physicians and patients in contributing to the cause of
these perforations. This study was conducted between April 2010 and May 2015 and
included 64 patients with perforated appendicitis. Patients' medical records were
examined for factors that might have contributed to perforation, and the roles of
patients and physicians in perforation appendicitis were evaluated. The
perforation rate of patients with appendicitis was 16.0 per cent. The average
duration from symptom onset to hospital admission was 4.4 days (29 patients were
admitted to hospital within two days, 35 were admitted later). In total, 38
patients had visited a different hospital before admission. Furthermore, six out
of 26 patients who had not visited any other hospital had consumed analgesics.
Factors contributing to appendix perforation included misdiagnosis at the
patient's initial visit (56.0%), delayed admission to hospital (11.0%), and use
of analgesics (9.0%). The cause of perforation was mostly physician-related in
children and adults, and patient-related in older adults.
PMID- 28424137
TI - Improvement of Treatment Outcomes after Implementation of a Massive Transfusion
Protocol: A Level I Trauma Center Experience.
AB - We assessed the effectiveness of the implementation of an institutional massive
transfusion protocol (MTP) for resuscitation with a 1:1:1 transfusion ratio of
packed red blood cell (PRBC), fresh frozen plasma, and platelet units. In a Level
I trauma center database, all trauma admissions (2004-2012) that received massive
transfusions (>=10 units PRBCs in the first 24 hours) were reviewed
retrospectively. Demographic data, transfusion ratios, and outcomes were compared
before (PRE) and after (POST) MTP implementation in May 2008. Age, sex, and
mechanism of injury were similar between 239 PRE and 208 POST trauma patients
requiring massive transfusion. Transfusion ratios of fresh frozen plasma:PRBC and
platelet:PRBC increased after MTP implementation. Among survivors, MTP
implementation shortened hospital length of stay from 31 to 26 days (P = 0.04)
and intensive care unit length of stay from 31 to 26 days (P = 0.02). Linear
regression identified treatment after (versus before) implementation of MTP as an
independent predictor of decreased ventilator days after adjusting for age,
Glasgow Coma Scale, and chest Abbreviated Injury Score (P < 0.0001). Modest
improvement in ratios likely does not account for all significant improvements in
outcomes. Implementing a standardized protocol likely impacts automation,
efficiency, and/or timeliness of product delivery.
PMID- 28424138
TI - Comparative Analysis of the Paravertebral Analgesic Pump Catheter with the
Epidural Catheter in Elderly Trauma Patients with Multiple Rib Fractures.
AB - Presently, trauma guidelines recommend epidural analgesia as the optimal modality
of pain relief from rib fractures. They are not ideally suited for elderly trauma
patients and have disadvantages including bleeding risk. The paravertebral
analgesic pump (PVP) eliminates such disadvantages and includes ease of placement
in the trauma setting. This study compares pain control in patients treated by
EPI versus PVP. This is a retrospective, historical cohort study comparing two
methods of pain management in the trauma setting. Before 2010, patients who had
epidural catheters (EPI) placed for pain control were compared with patients
after 2010 in which the PVP was used. All patients had multiple rib fractures as
diagnosed by CT scan. Analysis was adjusted for age, number of fractures, and
comorbid conditions. Multiple linear regression analysis was conducted to compare
average reported pain. A total of 110 patients, 31 PVP and 79 epidural catheters,
were included in the study. Overall mean age was 65 years. The mean Injury
Severity Score was 12.0 (EPI) and 11.1 (PVP). Mean number rib fractures was 4.29
(EPI) and 4.71 (PVP). PVP was associated with a 30 per cent greater decrease in
pain than that seen with EPI (6.0-1.9 vs 6.4-3.4). After controlling for age,
Injury Severity Score, and number of rib fractures, there were no differences in
intensive care unit or total length of stay (P = 0.35) or in pain score (3.76 vs
3.56, P = 0.64). In conclusion, the PVP compares well with epidural analgesia in
older trauma patients yet is safe, well tolerated, and easily inserted.
PMID- 28424139
TI - Lethal Trauma Pulmonary Embolism Is a Black Swan Event in Patients at Risk for
Deep Vein Thrombosis: An Evidence-Based Review.
AB - We delineated the incidence of trauma patient pulmonary embolism (PE) and risk
conditions by performing a systematic literature review of those at risk for deep
vein thrombosis (DVT). The PE proportion was 1.4 per cent (95% confidence
interval = 1.2-1.6) in at-risk patients. Of 10 conditions, PE was only associated
with increased age (P < 0.01) or leg injury (P < 0.01; risk ratio = 1.6). As
lower extremity DVT (LEDVT) proportions increased, mortality proportions (P =
0.02) and hospital stay (P = 0.0002) increased, but PE proportions did not (P =
0.13). LEDVT was lower with chemoprophylaxis (CP) (4.9%) than without CP (19.1%;
P < 0.01). PE was lower with CP (1.0%) than without CP (2.2%; P = 0.0004).
Mortality was lower with CP (6.6%) than without CP (11.6%; P = 0.002). PE was
similar with (1.2%) and without (1.9%; P = 0.19) mechanical prophylaxis (MP).
LEDVT was lower with MP (8.5%) than without MP (12.2%; P = 0.0005). PE
proportions were similar with (1.3%) and without (1.5%; P = 0.24) LEDVT
surveillance. Mortality was higher with LEDVT surveillance (7.9%) than without
(4.8%; P < 0.01). A PE mortality of 19.7 per cent (95% confidence interval = 18
22) * a 1.4 per cent PE proportion yielded a 0.28 per cent lethal PE proportion.
As PE proportions increased, mortality (P = 0.52) and hospital stay (P = 0.13)
did not. Of 176 patients with PE, 76 per cent had no LEDVT. In trauma patients at
risk for DVT, PE is infrequent, has a minimal impact on outcomes, and death is a
black swan event. LEDVT surveillance did not improve outcomes. Because PE was not
associated with LEDVT and most patients with PE had no LEDVT, preventing,
diagnosing, and treating LEDVT may be ineffective PE prophylaxis.
PMID- 28424140
TI - Impact of Multimodality Pain Regimens on Elective Colorectal Surgery Outcomes.
AB - Trials of enhanced recovery programs suggest that multimodality pain regimens
improve outcomes after colorectal surgery. We sought to determine whether
patients receiving postoperative multimodality pain regimens would have shorter
lengths of stay without an associated increase in readmission rate as compared to
those receiving opioid-based pain regimens. Retrospective cohort study of adults
who underwent elective colorectal surgery between January 1, 2006, and December
31, 2012, in a national hospital network participating in the Premier Perspective
database. Patients were grouped into multimodality or opioid-based using
postoperative medication charges. Primary outcome measures included length of
stay and 30-day readmission rate. Among 91,936 patients, 38 per cent received
multimodality pain regimens and 61 per cent received opioid-based regimens. After
adjustment for patient and surgical characteristics, there was no difference in
length of stay or cost, odds of readmission were 1.2 (95% confidence interval =
1.2-1.3, P < 0.001), and odds of mortality were 0.8 (95% confidence interval =
0.6-0.9, P < 0.001) in the multimodality group compared to nonopioid sparing. Our
results were consistent in secondary analyses using propensity matching. Fewer
than half of patients undergoing elective colorectal surgery in our cohort
received multimodality pain regimens, and receipt of these medications was
associated with mixed benefits in terms of length of stay, readmission, and
mortality.
PMID- 28424141
TI - Can Parathormon Levels after Ipsilateral Lobectomy Predict Postoperative
Hypocalcemia in Patients Undergoing Total Thyroidectomy?
AB - The purpose of this study was to investigate the relationship between the serum
parathormone (PTH) levels measured after completion of hemithyroidectomy on the
first side during total thyroidectomy and the postoperative hypocalcemia. The
patients were divided into two groups, as those who demonstrated a decrease in
PTH levels measured after completion of hemithyroidectomy of the first side
(Group 1, n = 43) and those who did not demonstrate a decrease in PTH levels
(Group 2, n = 24). The serum PTH levels were measured just before the incision
(PTHi), when the hemithyroidectomy stage had been completed (PTHht), at the end
of the operation (PTHtt), and at the postoperative 24th hour (PTH24hr). The serum
total calcium (Ca2+) levels were also measured. The median percentage differences
in PTHtt levels based on basal PTHi levels of Groups 1 and 2 were -60.6 and -15.7
per cent, respectively, P = 0.001. The frequency of postoperative biochemical
hypocalcemia was higher in Group 1, P < 0.05. It was determined that a 10 per
cent or higher decrease in PTHht levels in Group 1 could predict biochemical
hypocalcemia at the postoperative 24th hour. In conclusions, postoperative
hypocalcemia is seen more frequent in patients with a decrease of PTHht during
total thyroidectomy. A decrease of 10 per cent in PTHht levels measured after
ipsilateral lobectomy and a 62 per cent or higher decrease in PTHtt levels
measured in the end of the total thyroidectomy could be helpful for prediction of
postoperative hypocalcemia in these patients.
PMID- 28424142
TI - Advance care planning, culture and religion: an environmental scan of Australian
based online resources.
AB - Objectives Culture and religion are important in advance care planning (ACP), yet
it is not well understood how this is represented in ACP online resources. The
aim of the present study was to identify the availability of Australian-based ACP
websites and online informational booklets containing cultural and religious
information. Methods An environmental scanning framework was used with a Google
search conducted from 30 June 2015 to 5 July 2015. Eligible Australian-based ACP
websites and online informational booklets were reviewed by two analysts (APS &
PM) for information pertaining to at least one culture or religion. Common
characteristics were agreed upon and tabulated with narrative description.
Results Seven Australian-based ACP websites were identified with varying degrees
of cultural and religious information. Seven Australian-based ACP informational
booklets were identified addressing culture or religion, namely of Aboriginal and
Torres Strait Islander (n=5), Sikh (n=1) and Italian (n=1) communities. Twenty
one other online resources with cultural and religious information were
identified, developed within the context of health and palliative care.
Conclusions There is no comprehensive Australian-based ACP website or
informational booklet supporting ACP across several cultural and religious
contexts. Considering Australia's multicultural and multifaith population, such a
resource may be beneficial in increasing awareness and uptake of ACP. What is
known about the topic? Health professionals and consumers frequently use the
Internet to find information. Non-regulation has resulted in the proliferation of
ACP online resources (i.e. ACP websites and online informational booklets).
Although this has contributed to raising awareness of ACP, the availability of
Australian-based ACP online resources with cultural and religious information is
not well known. What does this paper add? This paper is the first to use an
environmental scanning methodology to identify Australian-based ACP websites and
online informational booklets with cultural and religious information. What are
the implications for practitioners? The results of this environmental scan
present the availability of Australian-based ACP websites and online
informational booklets containing cultural and religious information. A thorough
understanding may assist in identifying gaps for future ACP project planning and
policy objectives, consistent with meeting cultural and religious needs. This may
be beneficial for health professionals, consumers, health associations,
organisations and government policy makers concerned with ACP.
PMID- 28424143
TI - Correlates of sexually transmissible infection testing among a sample of at-risk
young Australians.
AB - Annual chlamydia testing is recommended for all sexually active Australians aged
15-29 years; however, the testing rate is below recommended levels. Three surveys
at a Melbourne music festival were conducted over 2012-14 to identify correlates
of sexually transmissible infection (STI) testing among young people at risk of
STIs. In total, 3588 participants were recruited; 72% reported having sex in the
past year. Based on sexual behaviours, 38% of sexually active participants were
classified as at risk of contracting STIs. In the past year, at-risk participants
had significantly higher odds of reporting a STI test (37%) than participants
classified as not at risk (24%) (OR=1.9; CI=1.6-2.3). Among at-risk participants,
correlates of STI testing in the past year included being aged 20-24 years,
visiting a GP, higher knowledge levels, earlier sexual debut and reporting more
than five lifetime partners. Testing rates in our sample did not meet levels
required to reduce chlamydia prevalence. However, the testing rate was higher in
at-risk participants than participants who were not at risk. Future programs
aiming to increase chlamydia testing should improve knowledge and promote the
importance of testing after risk exposure, particularly among 16- to 19-year
olds.
PMID- 28424144
TI - Expertise and infrastructure capacity impacts acute coronary syndrome outcomes.
AB - Objective Effective translation of evidence to practice may depend on systems of
care characteristics within the health service. The present study evaluated
associations between hospital expertise and infrastructure capacity and acute
coronary syndrome (ACS) care as part of the SNAPSHOT ACS registry. Methods A
survey collected hospital systems and process data and our analysis developed a
score to assess hospital infrastructure and expertise capacity. Patient-level
data from a registry of 4387 suspected ACS patients enrolled over a 2-week period
were used and associations with guideline care and in-hospital and 6-, 12- and 18
month outcomes were measured. Results Of 375 participating hospitals, 348 (92.8%)
were included in the analysis. Higher expertise was associated with increased
coronary angiograms (440/1329; 33.1%), 580/1656 (35.0%) and 609/1402 (43.4%) for
low, intermediate and high expertise capacity respectively; P<0.001) and the
prescription of guideline therapies observed a tendency for an association with
(531/1329 (40.0%), 733/1656 (44.3%) and 603/1402 (43.0%) for low, intermediate
and high expertise capacity respectively; P=0.056), but not rehabilitation
(474/1329 (35.7%), 603/1656 (36.4%) and 535/1402 (38.2%) for low, intermediate
and high expertise capacity respectively; P=0.377). Higher expertise capacity was
associated with a lower incidence of major adverse events (152/1329 (11.4%),
142/1656 (8.6%) and 149/149 (10.6%) for low, intermediate and high expertise
capacity respectively; P=0.026), as well as adjusted mortality within 18 months
(low vs intermediate expertise capacity: odds ratio (OR) 0.79, 95% confidence
interval (CI) 0.58-1.08, P=0.153; intermediate vs high expertise capacity: OR
0.64, 95% CI 0.48-0.86, P=0.003). Conclusions Both higher-level expertise in
decision making and infrastructure capacity are associated with improved evidence
translation and survival over 18 months of an ACS event and have clear healthcare
design and policy implications. What is known about the topic? There are
comprehensive guidelines for treating ACS patients, but Australia and New Zealand
registry data reveal substantial gaps in delivery of best practice care across
metropolitan, regional, rural and remote health services, raising questions of
equity of access and outcome. Greater mortality and morbidity gains can be
achieved by increasing the application of current evidence-based therapies than
by developing new therapy innovations. Health service system characteristics may
be barriers or enablers to the delivery of best practice care and need to be
identified and evaluated for correlations with performance indicators and
outcomes in order to improve health service design. What does this paper add?
This study measures two system characteristics, namely expertise and
infrastructure, evaluating the relationship with ACS guideline application and
clinical outcomes in a large and diverse cohort of Australian and New Zealand
hospitals. The study identifies decision-making expertise and infrastructure
capacity, to a lesser degree, as enabling characteristics to help improve patient
outcomes. What are the implications for practitioners? In the design of health
services to improve access and equity, expertise must be preserved. However, it
is difficult to have experienced personnel at the bedside no matter where the
health service, and engineering innovative systems and processes of care to
facilitate delivery of expertise should be considered.
PMID- 28424145
TI - 'We didn't have to dance around it': opt-out HIV testing among homeless and
marginalised patients.
AB - This study explored opt-out HIV testing in an Australian general practice. The
aims were to: (1) determine the effect of the opt-out approach on the number of
HIV tests performed; and (2) explore the acceptability of opt-out HIV testing
from the healthcare providers' perspective. A prospective mixed-methods study of
opt-out HIV testing over a 2-year period (March 2014-March 2016) was conducted.
Implementation was based on a theoretical framework that was developed
specifically for this study. The setting was Homeless Healthcare, a health
service in Perth, Western Australia. The number of HIV tests conducted during the
control year (usual practice) was compared with the intervention year (opt-out
testing). After the intervention, the healthcare providers (n=8) were interviewed
about their experiences with opt-out HIV testing. Directed content analysis was
used to explore the qualitative data. HIV testing rates were low during both the
control year and the intervention year (315 HIV tests (12% of the patient cohort)
and 344 HIV tests (10%) respectively). Opt-out HIV testing was feasible and
acceptable to the participating healthcare providers. Other health services could
consider opt-out HIV testing for their patients to identify people with
undiagnosed infections and sustain Australia's low HIV prevalence.
PMID- 28424146
TI - Excess all-cause and influenza-attributable mortality in Europe, December 2016 to
February 2017.
AB - Since December 2016, excess all-cause mortality was observed in many European
countries, especially among people aged >= 65 years. We estimated all-cause and
influenza-attributable mortality in 19 European countries/regions. Excess
mortality was primarily explained by circulation of influenza virus A(H3N2). Cold
weather snaps contributed in some countries. The pattern was similar to the last
major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in
line with the early influenza season start.
PMID- 28424147
TI - Treatment of Leukoencephalopathy With Calcifications and Cysts With Bevacizumab.
AB - BACKGROUND: Leukoencephalopathy with calcifications and cysts is a rare,
autosomal recessive cerebral microangiopathy that causes progressive white matter
disease, calcifications, and cysts within the brain. It is typically associated
with slowly progressive psychomotor regression, seizures, and movement disorders.
Although leukoencephalopathy with calcifications and cysts affects only the
central nervous system, it demonstrates remarkable neuropathologic and radiologic
overlap with Coats plus, a disorder of small vessels of the brain, eyes,
gastrointestinal tract, and bone. Coats disease without extraocular involvement,
a genetically distinct disorder from Coats plus, is characterized by retinal
telangiectasias and exudative retinopathy, accompanied by neovascularization.
Inhibition of vascular endothelial growth factor (VEGF) signaling with the
monoclonal anti-VEGF antibody bevacizumab can improve retinal edema and exudates
in Coats disease. Given these observations, we reasoned that VEGF inhibition
might also be effective in treating leukoencephalopathy with calcifications and
cysts and Coats plus, neither of which has any known therapy. METHODS: We treated
an 18-year-old man with leukoencephalopathy with calcifications and cysts using
biweekly infusions of the VEGF inhibitor bevacizumab for more than one year and
performed clinical examinations and brain imaging at three month intervals.
RESULTS: After treatment for more than one year, the patient showed improved
bradykinesia and range of motion, and brain magnetic resonance imaging
demonstrated a marked reduction in cyst volume and white matter lesions.
CONCLUSIONS: Further studies in a cohort of patients are warranted to investigate
the efficacy of VEGF inhibition as a treatment for leukoencephalopathy with
calcifications and cysts.
PMID- 28424148
TI - Evidence-based deprescribing of proton pump inhibitors in long-term care.
PMID- 28424151
TI - Parents against prohibition: campaigning for drug law reform.
PMID- 28424149
TI - Comparative Safety of Sulfonylurea and Metformin Monotherapy on the Risk of Heart
Failure: A Cohort Study.
AB - BACKGROUND: Medications that impact insulin sensitivity or cause weight gain may
increase heart failure risk. Our aim was to compare heart failure and
cardiovascular death outcomes among patients initiating sulfonylureas for
diabetes mellitus treatment versus metformin. METHODS AND RESULTS: National
Veterans Health Administration databases were linked to Medicare, Medicaid, and
National Death Index data. Veterans aged >=18 years who initiated metformin or
sulfonylureas between 2001 and 2011 and whose creatinine was <1.4 (females) or
1.5 mg/dL (males) were included. Each metformin patient was propensity score
matched to a sulfonylurea initiator. The outcome was hospitalization for acute
decompensated heart failure as the primary reason for admission or a
cardiovascular death. There were 126 867 and 79 192 new users of metformin and
sulfonylurea, respectively. Propensity score matching yielded 65 986 per group.
Median age was 66 years, and 97% of patients were male; hemoglobin A1c 6.9% (6.3,
7.7); body mass index 30.7 kg/m2 (27.4, 34.6); and 6% had heart failure history.
There were 1236 events (1184 heart failure hospitalizations and 52 cardiovascular
deaths) among sulfonylurea initiators and 1078 events (1043 heart failure
hospitalizations and 35 cardiovascular deaths) among metformin initiators. There
were 12.4 versus 8.9 events per 1000 person-years of use (adjusted hazard ratio
1.32, 95%CI 1.21, 1.43). The rate difference was 4 heart failure hospitalizations
or cardiovascular deaths per 1000 users of sulfonylureas versus metformin
annually. CONCLUSIONS: Predominantly male patients initiating treatment for
diabetes mellitus with sulfonylurea had a higher risk of heart failure and
cardiovascular death compared to similar patients initiating metformin.
PMID- 28424152
TI - Acute appendicitis.
PMID- 28424155
TI - Active commuting is beneficial for health.
PMID- 28424154
TI - Association between active commuting and incident cardiovascular disease, cancer,
and mortality: prospective cohort study.
AB - Objective To investigate the association between active commuting and incident
cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective
population based study. Setting UK Biobank.Participants 263 450 participants (106
674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The
exposure variable was the mode of transport used (walking, cycling, mixed mode v
non-active (car or public transport)) to commute to and from work on a typical
day.Main outcome measures Incident (fatal and non-fatal) CVD and cancer, and
deaths from CVD, cancer, or any causes.Results 2430 participants died (496 were
related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile
range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In
maximally adjusted models, commuting by cycle and by mixed mode including cycling
were associated with lower risk of all cause mortality (cycling hazard ratio
0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76,
0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001;
mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling
0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001).
Commuting by cycling and walking were associated with a lower risk of CVD
incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99,
P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45
to 0.91, P=0.01). No statistically significant associations were observed for
walking commuting and all cause mortality or cancer outcomes. Mixed mode
commuting including walking was not noticeably associated with any of the
measured outcomes.Conclusions Cycle commuting was associated with a lower risk of
CVD, cancer, and all cause mortality. Walking commuting was associated with a
lower risk of CVD independent of major measured confounding factors. Initiatives
to encourage and support active commuting could reduce risk of death and the
burden of important chronic conditions.
PMID- 28424156
TI - Kiran Patel: Eyes on the front line.
PMID- 28424157
TI - Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and
young adults in Sweden.
AB - Objective To examine the relation between childhood adversity, the role of school
performance, and childhood psychopathology and the risk of suicide.Design Cohort
study of register based indicators of childhood adversity (at ages 0-14)
including death in the family (suicide analysed separately), parental substance
abuse, parental psychiatric disorder, substantial parental criminality, parental
separation/single parent household, receipt of public assistance, and residential
instability.Setting Swedish medical birth register and various Swedish population
based registers.Participants 548 721 individuals born 1987-91.Main outcome
measures Estimates of suicide risk at ages 15-24 calculated as incidence rate
ratios adjusted for time at risk and confounders.Results Adjusted incidence rate
ratios for the relation between childhood adversity and suicide during
adolescence and young adulthood ranged from 1.6 (95% confidence interval 1.1 to
2.4) for residential instability to 2.9 (1.4 to 5.9) for suicide in the family.
There was a dose-response relation between accumulating childhood adversity and
risk: 1.1 (0.9 to 1.4) for those exposed to one adversity and 1.9 (1.4 to 2.5)
and 2.6 (1.9 to 3.4) for those exposed to two and three or more adversities,
respectively. The association with increased risk of suicide remained even after
adjustment for school performance and childhood psychopathology.Conclusion
Childhood adversity is a risk factor for suicide in adolescence and young
adulthood, particularly accumulated adversity. These results emphasise the
importance of understanding the social mechanisms of suicide and the need for
effective interventions early in life, aiming to alleviate the risk in
disadvantaged children.
PMID- 28424158
TI - Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping.
AB - Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in
mice and other model organisms. Modifications of traditional gene trap cassettes,
including addition of conditional features in the form of Flip-excision (FlEx)
arrays to enable directional gene trap cassette inversions by Cre and Flpe site
specific recombinases, greatly enhanced their experimental potential. By taking
advantage of these conditional gene trap cassettes, we developed a generic
strategy for generating conditional mutations and validated this strategy in mice
carrying a multipurpose allele of the Prdm16 transcription factor gene. We
demonstrate that the gene trap insertion creates a null mutation replicating the
Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice.
Consecutive breeding to Flpe and Emx1IREScre deleter mice spatially restricted
Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1,
demonstrating the utility of the technology for the analysis of tissue-specific
gene functions.
PMID- 28424159
TI - Prolonged Elimination of Negative Feedback Control Mechanisms Along the Insulin
Signaling Pathway Impairs beta-Cell Function In Vivo.
AB - Cellular stress and proinflammatory cytokines induce phosphorylation of insulin
receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-I
signaling. We therefore examined the effects of mutation of five "inhibitory" Ser
phosphorylation sites on IRS2 function in transgenic mice that overexpress,
selectively in pancreatic beta-cells, either wild-type (WT) or a mutated IRS2
protein (IRS25A). Islets size, number, and mRNA levels of catalase and superoxide
dismutase were increased, whereas those of nitric oxide synthase were decreased,
in 7- to 10-week-old IRS25A-beta mice compared with IRS2WT-beta mice. However,
glucose homeostasis and insulin secretion in IRS25A-beta mice were impaired when
compared with IRS2WT-beta mice or to nontransgenic mice. This was associated with
reduced mRNA levels of Glut2 and islet beta-cell transcription factors such as
Nkx6.1 and MafA Similarly, components mediating the unfolded protein response
were decreased in islets of IRS25A-beta mice in accordance with their decreased
insulin secretion. The beneficial effects of IRS25A on beta-cell proliferation
and beta-cell transcription factors were evident only in 5- to 8-day-old mice.
These findings suggest that elimination of inhibitory Ser phosphorylation sites
of IRS2 exerts short-term beneficial effects in vivo; however, their sustained
elimination leads to impaired beta-cell function.
PMID- 28424160
TI - Heterogeneous Nuclear Ribonucleoprotein F Stimulates Sirtuin-1 Gene Expression
and Attenuates Nephropathy Progression in Diabetic Mice.
AB - We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP
F) renoprotective action in a type 2 diabetes (T2D) mouse model (db/db).
Immortalized rat renal proximal tubular cells (IRPTCs) and kidneys from humans
with T2D were also studied. The db/db mice developed hyperglycemia, oxidative
stress, and nephropathy at age 20 weeks compared with their db/m littermates.
These abnormalities, with the exception of hyperglycemia, were attenuated in
db/dbhnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their
RPTCs. Sirtuin-1, Foxo3alpha, and catalase expression were significantly
decreased in RPTCs from db/db mice and normalized in db/dbhnRNP F-Tg mice. In
vitro, hnRNP F overexpression stimulated Sirtuin-1 and Foxo3alpha with
downregulation of acetylated p53 expression and prevented downregulation of
Sirtuin-1 and Foxo3alpha expression in IRPTCs by high glucose plus palmitate.
Transfection of Sirtuin-1 small interfering RNA prevented hnRNP F stimulation of
Foxo3alpha and downregulation of acetylated p53 expression. hnRNP F stimulated
Sirtuin-1 transcription via hnRNP F-responsive element in the Sirtuin-1 promoter.
Human T2D kidneys exhibited more RPTC apoptosis and lower expression of hnRNP F,
SIRTUIN-1, and FOXO3alpha than nondiabetic kidneys. Our results demonstrate that
hnRNP F protects kidneys against oxidative stress and nephropathy via stimulation
of Sirtuin-1 expression and signaling in diabetes.
PMID- 28424161
TI - Response and progression on midostaurin in advanced systemic mastocytosis: KIT
D816V and other molecular markers.
AB - In advanced systemic mastocytosis (advSM), disease evolution is often triggered
by KIT mutations (D816V in >80% of cases) and by additional mutations (eg, in
SRSF2, ASXL1, and/or RUNX1 [S/A/Rpos in >60% of cases]). In a recently reported
phase 2 study, midostaurin, a multikinase/KIT inhibitor, demonstrated an overall
response rate (ORR) of 60% in advSM but biomarkers predictive of response are
lacking. We evaluated the impact of molecular markers at baseline and during
follow-up in 38 midostaurin-treated advSM patients. The median overall survival
(OS) was 30 months (95% confidence interval, 6-54) from start of midostaurin. ORR
and OS were significantly different between S/A/Rneg (n = 12) and S/A/Rpos (n =
23) patients (ORR: 75% vs 39%, P = .04; OS: P = .01, HR 4.5 [1.3-16.2]).
Depending on the relative reduction of the KIT D816V expressed allele burden
(EAB) at month 6, patients were classified as KIT responders (>=25%, n = 17) or
KIT nonresponders (<25%, n = 11). In univariate analyses at month 6, reduction of
KIT D816V EAB >=25%, tryptase >=50%, and alkaline phosphatase >=50% were
significantly associated with improved OS. In multivariate analysis, only KIT
D816V EAB reduction >=25% remained an independent on-treatment marker for
improved OS (P = .004, HR 6.8 [1.8-25.3]). Serial next-generation sequencing
analysis of 28 genes in 16 patients revealed acquisition of additional mutations
or increasing variant allele frequency in K/NRAS, RUNX1, IDH2, or NPM1 associated
with progression in 7 patients. In midostaurin-treated advSM patients, the
complexity and dynamics of mutational profiles significantly affect response,
progression, and prognosis.
PMID- 28424162
TI - Pembrolizumab in patients with CLL and Richter transformation or with relapsed
CLL.
AB - Chronic lymphocytic leukemia (CLL) patients progressed early on ibrutinib often
develop Richter transformation (RT) with a short survival of about 4 months.
Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to
inhibit immune surveillance in CLL. This phase 2 study was designed to test the
efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a
dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five
patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell
lymphoma) patients were enrolled, and 60% received prior ibrutinib. Objective
responses were observed in 4 out of 9 RT patients (44%) and in 0 out of 16 CLL
patients (0%). All responses were observed in RT patients who had progression
after prior therapy with ibrutinib. After a median follow-up time of 11 months,
the median overall survival in the RT cohort was 10.7 months, but was not reached
in RT patients who progressed after prior ibrutinib. Treatment-related grade 3 or
above adverse events were reported in 15 (60%) patients and were manageable.
Analyses of pretreatment tumor specimens from available patients revealed
increased expression of PD-ligand 1 (PD-L1) and a trend of increased expression
in PD-1 in the tumor microenvironment in patients who had confirmed responses.
Overall, pembrolizumab exhibited selective efficacy in CLL patients with RT. The
results of this study are the first to demonstrate the benefit of PD-1 blockade
in CLL patients with RT, and could change the landscape of therapy for RT
patients if further validated. This trial was registered at
www.clinicaltrials.gov as #NCT02332980.
PMID- 28424163
TI - Clinical significance of somatic mutation in unexplained blood cytopenia.
AB - Unexplained blood cytopenias, in particular anemia, are often found in older
persons. The relationship between these cytopenias and myeloid neoplasms like
myelodysplastic syndromes is currently poorly defined. We studied a prospective
cohort of patients with unexplained cytopenia with the aim to estimate the
predictive value of somatic mutations for identifying subjects with, or at risk
of, developing a myeloid neoplasm. The study included a learning cohort of 683
consecutive patients investigated for unexplained cytopenia, and a validation
cohort of 190 patients referred for suspected myeloid neoplasm. Using granulocyte
DNA, we looked for somatic mutations in 40 genes that are recurrently mutated in
myeloid malignancies. Overall, 435/683 patients carried a somatic mutation in at
least 1 of these genes. Carrying a somatic mutation with a variant allele
frequency >=0.10, or carrying 2 or more mutations, had a positive predictive
value for diagnosis of myeloid neoplasm equal to 0.86 and 0.88, respectively.
Spliceosome gene mutations and comutation patterns involving TET2, DNMT3A, or
ASXL1 had positive predictive values for myeloid neoplasm ranging from 0.86 to
1.0. Within subjects with inconclusive diagnostic findings, carrying 1 or more
somatic mutations was associated with a high probability of developing a myeloid
neoplasm during follow-up (hazard ratio = 13.9, P < .001). The predictive values
of mutation analysis were confirmed in the independent validation cohort. The
findings of this study indicate that mutation analysis on peripheral blood
granulocytes may significantly improve the current diagnostic approach to
unexplained cytopenia and more generally the diagnostic accuracy of myeloid
neoplasms.
PMID- 28424164
TI - Hypoxic adaptation of leukemic cells infiltrating the CNS affords a therapeutic
strategy targeting VEGFA.
PMID- 28424167
TI - Rethinking the regulation of l-carnitine transport in skeletal muscle cells.
Focus on "Multiple AMPK activators inhibit l-carnitine uptake in C2C12 skeletal
muscle myotubes".
PMID- 28424165
TI - Suppression of B-cell development genes is key to glucocorticoid efficacy in
treatment of acute lymphoblastic leukemia.
AB - Glucocorticoids (GCs), including dexamethasone (dex), are a central component of
combination chemotherapy for childhood B-cell precursor acute lymphoblastic
leukemia (B-ALL). GCs work by activating the GC receptor (GR), a ligand-induced
transcription factor, which in turn regulates genes that induce leukemic cell
death. Which GR-regulated genes are required for GC cytotoxicity, which pathways
affect their regulation, and how resistance arises are not well understood. Here,
we systematically integrate the transcriptional response of B-ALL to GCs with a
next-generation short hairpin RNA screen to identify GC-regulated "effector"
genes that contribute to cell death, as well as genes that affect the sensitivity
of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in
suppression of B-cell development genes that is linked to therapeutic response.
Inhibition of phosphatidylinositol 3-kinase delta (PI3Kdelta), a linchpin in the
pre-B-cell receptor and interleukin 7 receptor signaling pathways critical to B
cell development (with CAL-101 [idelalisib]), interrupts a double-negative
feedback loop, enhancing GC-regulated transcription to synergistically kill even
highly resistant B-ALL with diverse genetic backgrounds. This work not only
identifies numerous opportunities for enhanced lymphoid-specific combination
chemotherapies that have the potential to overcome treatment resistance, but is
also a valuable resource for understanding GC biology and the mechanistic details
of GR-regulated transcription.
PMID- 28424166
TI - Applying fluid biomarkers to Alzheimer's disease.
AB - Alzheimer's disease (AD) is a common neurodegenerative disease that starts with a
clinically silent phase of a decade or more during which brain pathologies
accumulate predominantly in the medial temporal lobe but also elsewhere in the
brain. Network dysfunction and clinical symptoms typically appear when senile
plaque (amyloid-beta) and neurofibrillary tangle (tau) pathologies meet in the
brain parenchyma, producing synapse and neuronal loss. For plaque and tangle
pathologies, reliable fluid biomarkers have been developed. These require
sampling of cerebrospinal fluid. Reliable blood tests for plaque and tangle
pathologies are currently lacking, but blood tests for general neurodegeneration
have recently been developed. In AD, plaques and tangles often coexist with other
pathologies, including Lewy bodies, and to what extent these contribute to
symptoms is currently unknown. There are also important differential diagnoses
that may be possible to distinguish from AD with the aid of biomarkers. The scope
of this review is fluid biomarkers for AD and related pathologies. The purpose is
to provide the reader with an updated account of currently available fluid
biomarkers for AD and clinically relevant differential diagnoses.
PMID- 28424168
TI - MiR-9-5p promotes MSC migration by activating beta-catenin signaling pathway.
AB - Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages,
but the very limited number of cells that migrate to the damaged region strongly
restricts their therapeutic applications. Full understanding of mechanisms
regulating MSC migration will help to improve their migration ability and
therapeutic effects. Increasing evidence shows that microRNAs play important
roles in the regulation of MSC migration. In the present study, we reported that
miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs
with high migration ability. Overexpression of miR-9-5p promoted MSC migration,
whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate
the underlying mechanism, we screened the target genes of miR-9-5p and report for
the first time that CK1alpha and GSK3beta, two inhibitors of beta-catenin
signaling pathway, were direct targets of miR-9-5p in MSCs and that
overexpression of miR-9-5p upregulated beta-catenin signaling pathway. In line
with these data, inhibition of beta-catenin signaling pathway by FH535 decreased
the miR-9-5p-promoted migration of MSCs, while activation of beta-catenin
signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR
9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as
well as the reorganization of F-actin were affected by the expression of miR-9
5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration
by upregulating beta-catenin signaling pathway, shedding light on the
optimization of MSCs for cell replacement therapy through manipulating the
expression level of miR-9-5p.
PMID- 28424169
TI - Identification of the fatty acid activation site on human ClC-2.
AB - Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl
channel activators. Molecular and cellular mechanisms underlying this activation
were examined. Role of a four-amino acid PKA activation site, RGET691, of hClC-2
was investigated using wild-type (WT) and mutant (AGET, RGEA, and AGAA) hClC-2
expressed in 293EBNA cells as well as involvement of PKA, intracellular cAMP
concentration ([cAMP]i), EP2, or EP4 receptor agonist activity. All fatty acids
[lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid, and
elaidic acid] caused significant rightward shifts in concentration-dependent Cl-
current activation (increasing EC50s) with mutant compared with WT hClC-2
channels, without changing time and voltage dependence, current-voltage
rectification, or methadone inhibition of the channel. As with lubiprostone,
cobiprostone activation of hClC-2 occurred with PKA inhibitor (myristoylated
protein kinase inhibitor) present or when using double PKA activation site
(RRAA655/RGEA691) mutant. Cobiprostone did not activate human CFTR. Fatty acids
did not increase [cAMP]i in hClC-2/293EBNA or T84 cells. Using T84 CFTR knockdown
cells, cobiprostone increased hClC-2 Cl- currents without increasing [cAMP]i,
while PGE2 and forskolin-IBMX increased both. Fatty acids were not agonists of
EP2 or EP4 receptors. L-161,982, a supposed EP4-selective inhibitor, had no
effect on lubiprostone-activated hClC-2 Cl- currents but significantly decreased
T84 cell barrier function measured by transepithelial resistance and fluorescent
dextran transepithelial movement. The present findings show that RGET691 of hClC
2 (possible binding site) plays an important functional role in fatty acid
activation of hClC-2. PKA, [cAMP]i, and EP2 or EP4 receptors are not involved.
These studies provide the molecular basis for fatty acid regulation of hClC-2.
PMID- 28424170
TI - ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF
signaling and angiogenesis.
AB - Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria
play a critical role in growth factor-induced switch from a quiescent to an
angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible
ROS produced from different sources can coordinate to stimulate VEGF signaling
and drive the angiogenic process remains unknown. Using the cytosol- and
mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging,
here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP
oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min,
which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression
of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine
phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and
proliferation at the similar extent. Exogenous hydrogen peroxide (H2O2) or
overexpression of Nox4, which produces H2O2, increases mitochondrial ROS (mtROS),
which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H2O2
to promote mtROS production. Mechanistically, H2O2 increases S36 phosphorylation
of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by
siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation
defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC
migration, and proliferation. In summary, Nox4-derived H2O2 in part activates
Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and
angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS
induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which
drives sustained activation of angiogenesis signaling program.
PMID- 28424173
TI - Association between estimated glomerular filtration rate and outcomes in patients
with diabetic foot ulcers: a 3-year follow-up study.
AB - OBJECTIVE: End-stage renal disease and dialysis have been proven to be associated
with poor prognoses in diabetic foot ulcers (DFUs). However, it has rarely been
reported whether and to what extent milder renal insufficiency affects the
prognosis. The purpose of this study was to investigate the categorized impact of
estimated glomerular filtration (eGFR) on the outcomes of patients with DFU.
DESIGN AND METHODS: Three hundred and sixty-six DFU patients hospitalized in a
Chinese tertiary hospital were recruited and classified into 4 groups according
to the eGFRs as follows: normal (>=90), mildly reduced (60-89), moderately
reduced (30-59), and severely reduced (<30). These patients were followed-up for
an average of 37 months to observe the outcomes, including ulcer healing,
amputation, ulcer recurrence, cardiac or cerebrovascular events and death. The
associations between eGFR and the outcomes were analysed by Cox proportional
hazards models. RESULTS: Compared to patients with normal eGFR, patients with
moderately reduced eGFR had higher risk of healing failure (hazard ratio (HR) =
2.08, 95% confidence interval (CI): 1.13-3.82), cardiac events (HR = 5.25, 95%
CI: 2.17-12.89) and death (HR = 3.54, 95% CI: 1.36-9.20). Severely reduced eGFR
was associated with higher incidence of healing failure (HR = 2.84, 95% CI: 1.25
6.49) and death (HR = 4.45, 95% CI: 1.23-16.07). The impact of eGFR on ulcer
recurrence and cerebrovascular events was not observed in all groups.
CONCLUSIONS: Moderately and severely reduced eGFR in patients with DFU were
independent predictors for poor prognoses of both the limbs and the patients.
PMID- 28424174
TI - The clinical value of regular thyroid function tests during amiodarone treatment.
AB - OBJECTIVE: Amiodarone is used for the maintenance of sinus rhythm in patients
with arrhythmias, but thyroid dysfunction (amiodarone-induced thyrotoxicosis
(AIT) or amiodarone-induced hypothyroidism (AIH)) is a common adverse effect. As
the onset of AIT and AIH may be unpredictable, the value of long-term regular
monitoring of amiodarone treated patients for thyroid dysfunction is still
uncertain. DESIGN: We retrospectively documented the frequency at which overt
thyroid dysfunction was preceded by subclinical thyroid dysfunction. METHODS: We
included 303 patients treated with amiodarone between 1984 and 2007. AIT was
defined as a lowered TSH level with an elevated free thyroxine (FT4) and AIH was
defined as an elevated TSH level with a decreased or subnormal FT4. Subclinical
AIT was defined as a lowered TSH level with a normal FT4 and subclinical AIH as
an elevated TSH level with a normal FT4. RESULTS: 200 men and 103 women, aged 62
+/- 12.0 years, suffering from atrial (260) or ventricular (43) arrhythmias, were
evaluated. During a median follow-up of 2.8 (1.0-25) years, 44 patients developed
AIT and 33 AIH. In 42 (55%) patients who developed AIT/AIH, earlier thyroid
function tests showed no subclinical AIT or subclinical AIH. In 35 (45%)
patients, AIT/AIH was preceded by subclinical AIT or subclinical AIH (16/44 for
AIT and 19/33 for AIH). CONCLUSIONS: In a considerable proportion of patients who
developed AIT/AIH, earlier thyroid function tests showed no subclinical AIT/AIH.
Less than half of the patients with a subclinical event subsequently developed
overt AIT/AIH. This study provides data to reconsider the yield of regular
testing of thyroid function to predict overt thyroid dysfunction in amiodarone
treated patients.
PMID- 28424171
TI - European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition -
Chapter 2: Classification and terminologySupported by the EGS Foundation: Part 1:
Foreword; Introduction; Glossary; Chapter 2 Classification and Terminology.
PMID- 28424175
TI - Correction.
PMID- 28424176
TI - Archivist: Is appendicectomy really necessary?
PMID- 28424178
TI - Archivist: Joint injections and methotrexate in JIA: better together?
PMID- 28424177
TI - Developmental and behavioural associations of burns and scalds in children: a
prospective population-based study.
AB - OBJECTIVE: To investigate child developmental and behavioural characteristics and
risk of burns and scalds. DESIGN: Data on burns in children up to 11 years from
12 966 participants in the Avon Longitudinal Study of Parents and Children were
linked to developmental profiles measured before the burn injury. MEASURES:
Preinjury profiles of the children derived from maternal questionnaires completed
in pregnancy, and at 6, 18, 42, 47 and 54 months. Injury data collected by
questionnaire at 6, 15 and 24 months and 3.5, 4.5, 5.5, 6.5, 8.5 and 11 years of
age. RESULTS: Incidence: Burn rates were as follows: birth-2 years
71.9/1000/year; 2-4.5 years 42.2/1000/year; 5-11 years 14.3/1000/year. Boys <2
years were more likely to sustain burns, and girls had more burns between age 5
and 11 years. Medical attention was sought for 11% of burn injuries. Development:
Up to age 2 years, burns were more likely in children with the most advanced
gross motor developmental scores and the slowest fine motor development. Children
with coordination problems at 4.5 years of age had increased risk of burns
between 5 and 11 years. No associations were observed with cognitive skills.
Behaviour: At 3.5 years, the Strengths and Difficulties Questionnaire scores and
reported frequent temper tantrums predicted subsequent burns in primary school
age. After adjustment for confounders, burns in the preschool period were related
to gender and motor development, and in school-aged children, to frequent temper
tantrums, hyperactivity and coordination difficulties. CONCLUSION: Child factors
associated with increased risk of burns were male gender in infancy and female
gender at school age, advanced gross motor development, coordination
difficulties, hyperactivity and problems with emotional regulation.
PMID- 28424181
TI - Variability in the cardiometabolic effects of omega-3 long-chain PUFAs:
background diet, timing, and genetics.
PMID- 28424182
TI - Human milk oligosaccharides vary among populations.
PMID- 28424183
TI - Biomarker-calibrated nutrient intake and healthy diet index associations with
mortality risks among older and frail women from the Women's Health Initiative.
AB - Background: Although studies to date have confirmed the association between
nutrition and frailty, the impact of dietary intake and dietary patterns on
survivorship in those with frailty is yet to be examined in a well-powered cohort
with validated frailty status. Moreover, previous studies were limited by
measurement error from dietary self-reports.Objective: We derived biomarker
calibrated dietary energy and protein intakes to address dietary self-report
error. Using these data, we then evaluated the association of mortality in older
women with frailty and dietary intake and healthy diet indexes, such as the
alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension
(DASH) score, and the Dietary Inflammatory Index (DII).Design: The analytic
sample included 10,034 women aged 65-84 y with frailty and complete dietary data
from the Women's Health Initiative Observational Study. Frailty was assessed with
modified Fried's criteria. Dietary data were collected by food-frequency
questionnaire.Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths
occurred. The HRs showed progressively decreased rates of mortality in women with
higher calibrated dietary energy intakes (P-trend = 0.003), higher calibrated
dietary protein intakes (P-trend = 0.03), higher aMED scores (P-trend = 0.006),
and higher DASH scores (P-trend = 0.02). Although the adjusted point estimates of
HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles
on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38),
respectively, compared with women in the first quartile, no overall effect was
observed across quartiles (P-trend = 0.35). Subgroup analyses by chronic
morbidity or smoking status or by excluding women with early death did not
substantially change these findings.Conclusions: The current study highlights the
importance of nutrition in older, frail women. Diet quality and quantity should
be considered in managing persons with frailty.
PMID- 28424184
TI - Demographic, lifestyle, and genetic determinants of circulating concentrations of
25-hydroxyvitamin D and vitamin D-binding protein in African American and
European American women.
AB - Background: Vitamin D may have anticancer activities. The high prevalence of
vitamin D deficiency in African Americans (AAs) may be a contributing factor to
the cancer health disparities between AAs and European Americans
(EAs).Objectives: We compared concentrations of 25(OH)D and vitamin D-binding
protein (VDBP) in AA and EA women and investigated determinants of the vitamin D
biomarker concentrations in both populations.Design: We used data and
biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina
Breast Cancer Study (CBCS) and the Women's Circle of Health Study (WCHS) in the
African American Breast Cancer Epidemiology and Risk Consortium. We measured
plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67
vitamin D-related genes in AA women only.Results: AA women had lower 25(OH)D
concentrations than did EA women (mean +/- SD: 14.2 +/- 8.1 compared with 21.1 +/
11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean
+/- SD: 344 +/- 133 compared with 336 +/- 124 MUg/mL, respectively; P = 0.25).
With VDBP and other factors controlled for, the observed racial difference in
25(OH)D concentrations did not diminish. Relations of demographic and lifestyle
factors with 25(OH)D were similar between AA and EA women. Although none of the
genetic variants that have been identified in previous genome-wide association
studies of 25(OH)D concentrations in EAs were significant (P > 0.05) in AAs, AA
women who carried the allele of a functional single nucleotide polymorphism
rs4988235, which has been previously associated with lactase expression and
lactose tolerance, had higher dietary vitamin D intake and higher measured
25(OH)D concentrations.Conclusions: AA women have lower concentrations of total
25(OH)D than EA women do, but both groups have similar VDBP concentrations,
suggesting that there are lower concentrations of free 25(OH)D in AAs. Although
demographic and lifestyle determinants of 25(OH)D concentrations are similar
between the 2 groups, genetic determinants may be ethnicity specific. Larger
studies in AAs will be needed to fully elucidate the underlying determinants of
low vitamin D concentrations in AA populations.
PMID- 28424185
TI - Very-long-chain omega-3 fatty acid supplements and adipose tissue functions: a
randomized controlled trial.
AB - Background: Increased omega-3 (n-3) fatty acid consumption is reported to benefit
patients with metabolic syndrome, possibly due to improved adipose tissue
function.Objective: We tested the effects of high-dose, very-long-chain omega-3
fatty acids on adipose tissue inflammation and insulin regulation of
lipolysis.Design: A double-blind, placebo-controlled study compared 6 mo of 3.9 g
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/d (4.2 g total omega
3/d; n = 12) with a placebo (4.2 g oleate/d; n = 9) in insulin-resistant adults.
Before and after treatment, the volunteers underwent adipose tissue biopsies to
measure the total (CD68+), pro- (CD14+ = M1), and anti- (CD206+ = M2)
inflammatory macrophages, crown-like structures, and senescent cells, as well as
a 2-step pancreatic clamping with a [U-13C]palmitate infusion to determine the
insulin concentration needed to suppress palmitate flux by 50%
(IC50(palmitate)f).Results: In the omega-3 group, the EPA and DHA contributions
to plasma free fatty acids increased (P = 0.0003 and P = 0.003, respectively), as
did the EPA and DHA content in adipose tissue (P < 0.0001 and P < 0.0001,
respectively). Despite increases in adipose and plasma EPA and DHA in the omega-3
group, there were no significant changes in the IC50(palmitate)f (19 +/- 2
compared with 24 +/- 3 MUIU/mL), adipose macrophages (total: 31 +/- 2/100
adipocytes compared with 33 +/- 2/100 adipocytes; CD14+: 13 +/- 2/100 adipocytes
compared with 14 +/- 2/100 adipocytes; CD206+: 28 +/- 2/100 adipocytes compared
with 29 +/- 3/100 adipocytes), crown-like structures (1 +/- 0/10 images compared
with 1 +/- 0/10 images), or senescent cells (4% +/- 1% compared with 4% +/- 1%).
There were no changes in these outcomes in the placebo group.Conclusions: Six
months of high-dose omega-3 supplementation raised plasma and adipose omega-3
fatty acid concentrations but had no beneficial effects on adipose tissue
lipolysis or inflammation in insulin-resistant adults. This trial was registered
at clinicaltrials.gov as NCT01686568.
PMID- 28424187
TI - A Mediterranean diet lowers blood pressure and improves endothelial function:
results from the MedLey randomized intervention trial.
AB - Background: The consumption of a Mediterranean diet (MedDiet) is associated with
a lower risk of cardiovascular disease. However, its impact on blood pressure and
endothelial function is not clear.Objective: We sought to determine the effects
of adhering to the consumption of a MedDiet for 6 mo on blood pressure and
endothelial function in older, healthy Australians.Design: A total of 166 men and
women aged >64 y were allocated via minimization to consume either a MedDiet (n =
85) or their habitual diet (HabDiet; control: n = 81) for 6 mo. The MedDiet
comprised mainly plant foods, abundant extra-virgin olive oil, and minimal red
meat and processed foods. A total of 152 participants commenced the study, and
137 subjects completed the study. Home blood pressure was measured on 5
consecutive days at baseline (n = 149) and at 3 and 6 mo. Endothelial function (n
= 82) was assessed by flow-meditated dilatation (FMD) at baseline and 6 mo.
Dietary intake was monitored with the use of 3-d weighed food records. Data were
analyzed with the use of linear mixed-effects models to determine adjusted
between-group differences.Results: The MedDiet adherence score increased
significantly in the MedDiet group but not in the HabDiet group (P < 0.001). The
MedDiet, compared with the HabDiet, resulted in lower systolic blood pressure (P
diet * time interaction = 0.02) [mean: -1.3 mm Hg (95% CI: -2.2, -0.3 mm Hg; P =
0.008) at 3 mo and -1.1 mm Hg (95% CI: -2.0, -0.1 mm Hg; P = 0.03) at 6 mo]. At 6
mo, the percentage of FMD was higher by 1.3% (95% CI: 0.2%, 2.4%; P = 0.026) in
the MedDiet group.Conclusion: Australian men and women who consumed a MedDiet for
6 mo had small but significantly lower systolic blood pressure and improved
endothelial function. This trial was registered at www.anzctr.org.au as
ACTRN12613000602729.
PMID- 28424186
TI - Circulating concentrations of biomarkers and metabolites related to vitamin
status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and
Australian populations.
AB - Background: Circulating concentrations of biomarkers that are related to vitamin
status vary by factors such as diet, fortification, and supplement use. Published
biomarker concentrations have also been influenced by the variation across
laboratories, which complicates a comparison of results from different
studies.Objective: We robustly and comprehensively assessed differences in
biomarkers that are related to vitamin status across geographic regions.Design:
The trial was a cross-sectional study in which we investigated 38 biomarkers that
are related to vitamin status and one-carbon and tryptophan metabolism in serum
and plasma from 5314 healthy control subjects representing 20 cohorts recruited
from the United States, Nordic countries, Asia, and Australia, participating in
the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized
laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'
phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and
alpha-tocopherol as well as combined vitamin scores that were based on these
nutrients showed that the general B-vitamin concentration was highest in the
United States and that the B vitamins and lipid soluble vitamins were low in
Asians. Conversely, circulating concentrations of metabolites that are inversely
related to B vitamins involved in the one-carbon and kynurenine pathways were
high in Asians. The high B-vitamin concentration in the United States appears to
be driven mainly by multivitamin-supplement users.Conclusions: The observed
differences likely reflect the variation in intake of vitamins and, in
particular, the widespread multivitamin-supplement use in the United States. The
results provide valuable information about the differences in biomarker
concentrations in populations across continents.
PMID- 28424188
TI - Nutritional profile of Supplemental Nutrition Assistance Program household food
and beverage purchases.
AB - Background: The Supplemental Nutrition Assistance Program (SNAP), which is the
largest federal nutrition assistance program in the United States, serves nearly
1 of 7 Americans. To date, few studies have examined food and beverage purchase
behaviors in SNAP participants with the use of electronic purchase
data.Objective: In this cross-sectional study, we examined household store
purchases of key food, beverage, and nutrient groups in SNAP participants and
nonparticipants.Design: Using a data set of US households' (n = 98,256 household
by-quarter observations) packaged food and beverage purchases and SNAP status
[current participant, income-eligible nonparticipant (income <=130% of the
Federal Poverty Level [FPL]), and higher-income nonparticipants (income >130% of
the FPL)] from 3 quarters during 2012-2013, we estimated pooled ordinary least
squares models, clustered at the household level, to examine the association
between SNAP status and purchases while controlling for sociodemographic
characteristics. We examined purchases of health- and policy-relevant food and
beverage groups [e.g., fruit and sugar-sweetened beverages (SSBs)] and nutrients
(e.g., total calories and sodium).Results: Regardless of SNAP status, households
had low mean purchases of fruit, vegetables, and fiber and high mean purchases of
junk foods, saturated fat, and sodium. After adjustment for multiple comparisons
and demographic characteristics, we found significant differences by SNAP status
of purchases of fruit, processed meat, salty snacks, sweeteners and toppings,
SSBs, and total calories, fiber, sugar, and sodium. Several of these differences
were clinically important. For example, compared with income-eligible and higher
income nonparticipants, SNAP participants purchased an additional ~15-20 kcal .
person-1 . d-1 from SSBs (P < 0.0001) and ~174-195 mg total Na . person-1 . d-1
(P <0.0001). Results were robust to corrections for sample-selection bias and to
the exclusion of observations with potentially misreported SNAP
status.Conclusions: American households, including SNAP households, show room for
improvement in the nutritional quality of store purchases. New interventions and
policies may be needed to improve food and beverage purchases in both SNAP and
non-SNAP households.
PMID- 28424189
TI - Diagnostic criteria for severe acute malnutrition among infants aged under 6 mo.
AB - Background: There is an increasing recognition of malnutrition among infants
under 6 mo of age (U6M). Current diagnosis criteria use weight-for-length z
scores (WLZs), but the 2006 WHO standards exclude infants shorter than 45 cm. In
older children, midupper arm circumference (MUAC) predicts mortality better than
does WLZ. Outcomes may also be influenced by exposure to HIV and size or
gestational age at birth. Diagnostic thresholds for WLZ, MUAC, and other indexes
have not been fully evaluated against mortality risk among U6M infants.Objective:
The aim was to determine the association of anthropometric indexes with risks of
inpatient and postdischarge mortality among U6M infants recruited at the time of
hospitalization.Design: We analyzed data from a cohort of U6M infants admitted to
Kilifi County Hospital (2007-2013), Kenya. The primary outcomes were inpatient
death and death during follow-up over 1 y after discharge. We calculated adjusted
RRs for inpatient mortality and HRs for postdischarge mortality for different
anthropometric measures and thresholds. Discriminatory value was assessed by
using receiver operating characteristic curves.Results: A total of 2882 infants
were admitted: 140 (4.9%) died in the hospital and 1405 infants were followed up
after discharge. Of these, 75 (5.3%) died within 1 y during 1318 child-years of
observation. MUAC and weight-for-age z score (WAZ) predicted inpatient and
postdischarge mortality better than did WLZ (P < 0.0001). A single MUAC threshold
of <11.0 cm performed similarly to MUAC thresholds that varied with age (all P >
0.05) and performed better than WLZ <-3 for both inpatient and postdischarge
mortality (both P < 0.001). Reported small size at birth did not reduce the risk
of death associated with anthropometric indexes.Conclusions: U6M infants at the
highest risk of death are best targeted by using MUAC or WAZ. Further research
into the effectiveness of potential interventions is required.
PMID- 28424191
TI - The D-lemma: narrow-band UV type B radiation versus vitamin D supplementation
versus sunlight for cardiovascular and immune health.
PMID- 28424190
TI - Odd-chain fatty acids as a biomarker for dietary fiber intake: a novel pathway
for endogenous production from propionate.
AB - Background: The risk of type 2 diabetes is inversely correlated with plasma
concentrations of odd-chain fatty acids [OCFAs; pentadecanoic acid (15:0) and
heptadecanoic acid (17:0)], which are considered as biomarkers for dairy fat
intake in humans. However, rodent studies suggest that OCFAs are synthesized
endogenously from gut-derived propionate. Propionate increases with dietary fiber
consumption and has been shown to improve insulin sensitivity.Objective: We
hypothesized that OCFAs are produced in humans from dietary fibers by a novel
endogenous pathway.Design: In a randomized, double-blind crossover study, 16
healthy individuals were supplemented with cellulose (30 g/d), inulin (30 g/d),
or propionate (6 g/d) for 7 d. In addition, human hepatoma cells were incubated
with different propionate concentrations. OCFAs were determined in plasma
phospholipids and hepatoma cells by gas chromatography.Results: Cellulose did not
affect plasma OCFA levels, whereas inulin and propionate increased pentadecanoic
acid by ~17% (P < 0.05) and 13% (P = 0.05), respectively. The effect on
heptadecanoic acid was even more pronounced, because it was elevated in almost
all participants by inulin (11%; P < 0.01) and propionate (13%; P < 0.001).
Furthermore, cell culture experiments showed a positive association between
propionate and OCFA levels (R2 = 0.99, P < 0.0001), whereas palmitate (16:0) was
negatively correlated (R2 = 0.83, P = 0.004).Conclusions: Our data show that gut
derived propionate is used for the hepatic synthesis of OCFAs in humans. The
association of OCFAs with a decreased risk of type 2 diabetes may therefore also
relate to dietary fiber intake and not only dairy fat. This trial was registered
at www.germanctr.de as DRKS00010121.
PMID- 28424192
TI - Sodium, sugar, and fat content of complementary infant and toddler foods sold in
the United States, 2015.
AB - Background: As part of a healthy diet, limiting intakes of excess sodium, added
sugars, saturated fat, and trans fat has been recommended. The American Heart
Association recommends that children aged <2 y should avoid added
sugars.Objective: We sought to determine commercial complementary infant-toddler
food categories that were of potential concern because of the sodium, added
sugar, saturated fat, or trans fat content.Design: Nutrition label information
(e.g., serving size, sodium, saturated fat, trans fat) for 1032 infant and
toddler foods was collected from manufacturers' websites and stores from May to
July 2015 for 24 brands, which accounted for >95% of infant-toddler food sales.
The presence of added sugars was determined from the ingredient list. Reference
amount customarily consumed (RACC) categories were used to group foods and
standardize serving sizes. A high sodium content was evaluated on the basis of
the Upper Intake Level for children aged 1-3 y and the number of potential
servings per day ([i.e., 1500 mg/7 servings (>210 mg/RACC)], a sodium amount >200
mg/100 g, or a mean sodium density >1000 mg/1000 kcal.Results: In 2015, most
commercial infant-only vegetables, fruit, dinners, and cereals were low in
sodium, contained no saturated fat, and did not contain added sugars. On average,
toddler meals contained 2233 mg Na/1000 kcal, and 84% of the meals had >210 mg
Na/RACC (170 g), whereas 69% of infant-toddler savory snacks had >200 mg Na/100
g. More than 70% of toddler meals, cereal bars and breakfast pastries, and infant
toddler grain- or dairy-based desserts contained >=1 sources of added sugar.
Approximately 70% of toddler meals contained saturated fat (mean: 1.9 g/RACC),
and no commercial infant-toddler foods contained trans fats.Conclusion: Most
commercial toddler meals, cereal bars and breakfast pastries, and infant-toddler
snacks and desserts have high sodium contents or contain added sugars, suggesting
a need for continued public health efforts to support parents in choosing
complementary foods for their infants and toddlers.
PMID- 28424193
TI - Study Suggests Treatment Approaches for Cholangiocarcinomas.
AB - A comprehensive genome profile of cholangiocarcinoma reveals that the tumors fall
into four molecular classes. The study suggests that patients with IDH1/2
mutations could benefit from drugs that inhibit oxidative phosphorylation or that
target mutations in chromatin remodeling genes. The work also shows that some
liver cancers are closely related to cholangiocarcinomas.
PMID- 28424194
TI - Common care practices among effective community-based specialist palliative care
teams: a qualitative study.
AB - OBJECTIVE: Evidence has shown that, despite wide variation in models of care,
community-based specialist palliative care teams can improve outcomes and reduce
acute care use at end of life. The goal of this study was to explore similarities
in care practices among effective and diverse specialist teams to inform the
development of other community-based teams. METHODS: Interviews with 78 providers
and administrators from 11 distinct community-based specialist palliative care
teams from Ontario, Canada were conducted. Interviews were audio-recorded,
transcribed and analysed using an inductive approach to identify common themes.
RESULTS: 3 key themes across all teams emerged. First, the distinct models of
care were generally summarised into 3 models: primary care and specialist
providers either collaborated by transferring, sharing or consulting in care.
Second, teams explicitly or implicitly followed 7 common care practices related
to: specialised expertise 24/7; intrateam communication; timeliness; physical
symptom and psychosocial-spiritual management; education; peace and fulfilment;
and advocacy for patient preferences. Third, all teams emphasised the importance
of team building, even more than using clinical tools and processes. CONCLUSIONS:
Despite wide variation in models of care among community-based specialist
palliative care teams, this large qualitative study identified several common
themes in care practices that can guide the development of other teams.
PMID- 28424195
TI - Thyroid skeletal metastasis: pain management with verteblation.
AB - The combination of percutaneous vertebroplasty with radiofrequency ablation
(verteblation) has not shown to be an effective measure of pain management in
patients with metastatic lesions of the spine. The use of this novel technique
has not been previously described in metastatic disease from thyroid cancer. We
would like to report our experience after treating a patient affected by a
thyroid carcinoma and an osteolytic spine metastasis. The patient suffered from
life-limiting pain and was successfully treated with a combination of
vertebroplasty and radiofrequency ablation. This case shows that the indications
of verteblation may be expanded in the palliative treatment of metastatic disease
from thyroid carcinoma.
PMID- 28424199
TI - Further research supports association between antidepressant use and elevated
risk of postpartum haemorrhage.
PMID- 28424198
TI - Pneumococcal Capsular Polysaccharide Immunity in the Elderly.
AB - Immunity to pneumococcal infections is impaired in older people, and current
vaccines are poorly protective against pneumococcal disease in this population.
Naturally acquired immunity to pneumococcal capsular polysaccharides develops
during childhood and is robust in young adults but deteriorates with advanced
age. In particular, antibody levels and function are reduced in older people.
Pneumococcal vaccines are recommended for people >65 years old. However, the
benefits of polysaccharide and protein-conjugated vaccines in this population are
small, because of both serotype replacement and incomplete protection against
vaccine serotype pneumococcal disease. In this review, we overview the immune
mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular
polysaccharide immunity declines with age, including altered colonization
dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired
mucosal immunity.
PMID- 28424200
TI - Whole-Exome Sequencing of Metaplastic Breast Carcinoma Indicates Monoclonality
with Associated Ductal Carcinoma Component.
AB - Purpose: Although most human cancers display a single histology, there are
unusual cases where two or more distinct tissue types present within a primary
tumor. One such example is metaplastic breast carcinoma, a rare but aggressive
cancer with a heterogeneous histology, including squamous, chondroid, and spindle
cells. Metaplastic carcinomas often contain an admixed conventional ductal
invasive or in situ mammary carcinoma component, and are typically triple
negative for estrogen receptor, progesterone receptor, and HER-2
amplification/overexpression. An unanswered question is the origin of metaplastic
breast cancers. While they may arise independently from their ductal components,
their close juxtaposition favors a model that postulates a shared origin, either
as two derivatives from the same primary cancer or one histology as an outgrowth
of the other. Understanding the mechanism of development of these tumors may
inform clinical decisions.Experimental Design: We performed exome sequencing for
paired metaplastic and adjacent conventional invasive ductal carcinomas in 8
patients and created a pipeline to identify somatic variants and predict their
functional impact, without having normal tissue. We then determined the genetic
relationships between the histologically distinct compartments.Results: In each
case, the tumor components have nearly identical landscapes of somatic mutation,
implying that the differing histologies do not derive from genetic clonal
divergence.Conclusions: A shared origin for tumors with differing histologies
suggests that epigenetic or noncoding changes may mediate the metaplastic
phenotype and that alternative therapeutic approaches, including epigenetic
therapies, may be required for metaplastic breast cancers. Clin Cancer Res;
23(16); 4875-84. (c)2017 AACR.
PMID- 28424201
TI - PIK3CA Mutations Contribute to Acquired Cetuximab Resistance in Patients with
Metastatic Colorectal Cancer.
AB - Purpose: Mutations in KRAS are considered to be the main drivers of acquired
resistance to epidermal growth factor receptor (EGFR) blockade in patients with
metastatic colorectal cancer (mCRC). However, the potential role of other genes
downstream of the EGFR signaling pathway in conferring acquired resistance has
not been extensively investigated.Experimental Design: Using circulating tumor
DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we
developed a targeted amplicon ultra-deep sequencing method to screen for low
abundance somatic mutations in a panel of genes that encode components of the
EGFR signaling pathway. Mutations with significantly increased variant
frequencies upon disease progression were selected by using quartile analysis.
The functional consequences of the identified mutations were validated in
cultured cells.Results: We analyzed 32 patients with acquired cetuximab
resistance in a development cohort. Of them, seven (22%) carried five novel
PIK3CA mutations, whereas eight (25%) carried previously reported KRAS mutations.
Functional studies showed that novel PIK3CA mutations (all in exon 19; p.K944N,
p.F930S, p.V955G, p.V955I, and p.K966E) promote cell viability in the presence of
cetuximab. Only one novel PIK3CA mutation (p.K944N) was verified in one of the 27
patients with acquired resistance in a validation cohort, simultaneous KRAS and
PIK3CA hotspot mutations were detected in two patients. Among the above 59
acquired resistance patients, those with PIK3CA or RAS mutations detected in
ctDNA showed a pronounced decrease in progression-free survival than patients
with no mutation.Conclusions: The PIK3CA mutations may potentially contribute to
acquired cetuximab resistance in patients with mCRC. Clin Cancer Res; 23(16);
4602-16. (c)2017 AACR.
PMID- 28424203
TI - Relationships between the timing of budburst, plant traits, and distribution of
24 coexisting woody species in a warm-temperate forest in Japan.
AB - PREMISE OF THE STUDY: Timing of budburst (DBB) may be related to the functional
traits and distributions of woody species in temperate regions. Although many
previous studies have investigated DBB in a number of temperate species, it has
seldom been linked to multiple plant trait relationships. METHODS: DBB and plant
traits were investigated for 24 woody species for 2 years in a warm-temperate
secondary forest in Japan. Particular attention was paid to differences in trait
relationships between coexisting deciduous and evergreen broad-leaved species.
KEY RESULTS: DBB was correlated with plant traits in deciduous but not evergreen
broad-leaved species; DBB was later for deciduous species with greater leaf mass,
leaf area, vessel diameter, and leaf nitrogen content per unit mass. In addition,
DBB was later for species with more northern distributions in deciduous and
evergreen species. CONCLUSIONS: Clear differences in the trait relationships
between deciduous and evergreen broad-leaved species might be caused by different
selection pressures on DBB; selection is expected to be more severe in deciduous
species. Overall, the continuous variable of vessel diameter might be used as a
simple and effective trait to predict DBB of deciduous species regardless of wood
anatomy; however, no such traits were detected as effective predictors of DBB in
evergreen species at this study site. In addition, DBB was earlier for the
species of more southern distributions, suggesting that such species benefit more
from warming.
PMID- 28424202
TI - Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic
Cysts.
AB - Purpose: Pancreatic cysts are estimated to be present in 2%-3% of the adult
population. Unfortunately, current diagnostics do not accurately distinguish
benign cysts from those that can progress into invasive cancer. Misregulated
pericellular proteolysis is a hallmark of malignancy, and therefore, we used a
global approach to discover protease activities that differentiate benign
nonmucinous cysts from premalignant mucinous cysts.Experimental Design: We
employed an unbiased and global protease profiling approach to discover protease
activities in 23 cyst fluid samples. The distinguishing activities of select
proteases was confirmed in 110 samples using specific fluorogenic substrates and
required less than 5 MUL of cyst fluid.Results: We determined that the activities
of the aspartyl proteases gastricsin and cathepsin E are highly increased in
fluid from mucinous cysts. IHC analysis revealed that gastricsin expression was
associated with regions of low-grade dysplasia, whereas cathepsin E expression
was independent of dysplasia grade. Gastricsin activity differentiated mucinous
from nonmucinous cysts with a specificity of 100% and a sensitivity of 93%,
whereas cathepsin E activity was 92% specific and 70% sensitive. Gastricsin
significantly outperformed the most widely used molecular biomarker,
carcinoembryonic antigen (CEA), which demonstrated 94% specificity and 65%
sensitivity. Combined analysis of gastricsin and CEA resulted in a near perfect
classifier with 100% specificity and 98% sensitivity.Conclusions: Quantitation of
gastricsin and cathepsin E activities accurately distinguished mucinous from
nonmucinous pancreatic cysts and has the potential to replace current diagnostics
for analysis of these highly prevalent lesions. Clin Cancer Res; 23(16); 4865-74.
(c)2017 AACR.
PMID- 28424204
TI - A species on a tightrope: Establishment limitations of an endangered lichen in a
fragmented Mediterranean landscape.
AB - PREMISE OF THE STUDY: Habitat loss and forest fragmentation affect the dispersal
and establishment of species. Furthermore, populations growing far from the
species' optimal climate might be less viable because good-quality habitat can be
scarce and easily altered by smaller changes. The lichen Pectenia plumbea has
oceanic climatic requirements, so in the Mediterranean region it needs the
humidity provided by well-preserved forests to thrive, but most of this habitat
has disappeared and the remnants are fragmented. In central Spain, this species
occupies only a small proportion of the existing forests, so we aimed to
determine whether this scattered distribution is due to limitations on dispersal
or establishment. METHODS: We selected a Mediterranean fragmented forest surface
in central Spain and extracted environmental variables from 371 plots. We modeled
the presence and abundance of P. plumbea and developed species distribution
models (SDMs) to detect all the suitable habitats inside the Cabaneros National
Park area. KEY RESULTS: Pectenia plumbea was present in most of the habitats
predicted as good-quality and was generally absent from the poor-quality zones
(85.9% overall success). The abundance correlated fairly well with that predicted
by the SDM (67%). Both models show that P. plumbea is linked to high temperature
and precipitation. CONCLUSIONS: Good-quality habitat requirements for P. plumbea
that are similar to oceanic conditions are found only in specific forested, stony
slopes derived from historical land management. This habitat is scarce, but P.
plumbea has successfully tracked all of these scattered areas via its high
dispersal capacity.
PMID- 28424205
TI - The use of soil pollen to determine the sex of overhead individuals of a
temperate dioecious shrub.
AB - PREMISE OF THE STUDY: In dioecious species, determining the sex of individual
plants from one-time phenological observations is rarely feasible when some
individuals capable of reproducing are not flowering or fruiting at the time of
observation. Currently, sexing those individuals requires long-term phenological
data on individuals and populations, but such data are rarely available or
feasible to collect. We tested the hypothesis that differences in soil pollen
concentrations beneath the crowns of female and male plants would exist and be
sufficient to reliably determine the sex of the individual plant overhead in a
dioecious species. We predicted that soil pollen concentrations beneath male
plants would be significantly higher than beneath female plants because only
males produce pollen and pollen should accumulate in the soil underneath the male
plants over repeated flowering events. METHODS: We collected samples from surface
soil under both sexes of the insect-pollinated dioecious shrub, Aucuba japonica
(Garryaceae). KEY RESULTS: Pollen grains were present in surface soil in both Oe
and A horizons, and mean pollen concentration under males was significantly
higher than under females. Pollen concentrations beneath males were positively
correlated with male plant height, potentially reflecting greater pollen
production by larger individuals. CONCLUSIONS: Considering the small plant size
and relatively low pollen production of A. japonica, this method may hold promise
for sexing other dioecious species in the absence of direct phenological data.
Our phenology-free and relatively low-cost method for sexing dioecious plants may
be especially useful in tropical forests where many species are dioecious.
PMID- 28424206
TI - Extending the fossil record of Polytrichaceae: Early Cretaceous Meantoinea
alophosioides gen. et sp. nov., permineralized gametophytes with gemma cups from
Vancouver Island.
AB - PREMISE OF THE STUDY: Diverse in modern ecosystems, mosses are dramatically
underrepresented in the fossil record. Furthermore, most pre-Cenozoic mosses are
known only from compression fossils, lacking detailed anatomical information.
When preserved, anatomy vastly improves resolution in the systematic placement of
fossils. Lower Cretaceous deposits at Apple Bay (Vancouver Island, British
Columbia, Canada) contain a diverse anatomically preserved flora that includes
numerous bryophytes, many of which have yet to be characterized. Among them is a
polytrichaceous moss that is described here. METHODS: Fossil moss gametophytes
preserved in four carbonate concretions were studied in serial sections prepared
using the cellulose acetate peel technique. KEY RESULTS: We describe Meantoinea
alophosioides gen. et sp. nov., a polytrichaceous moss with terminal gemma cups
containing stalked, lenticular gemmae. Leaves with characteristic costal anatomy,
differentiated into sheathing base and free lamina and bearing photosynthetic
lamellae, along with a conducting strand in the stem, place Meantoinea in family
Polytrichaceae. The bistratose leaf lamina with an adaxial layer of mamillose
cells, short photosynthetic lamellae restricted to the costa, and presence of
gemma cups indicate affinities with basal members of the Polytrichaceae, such as
Lyellia, Bartramiopsis, and Alophosia. CONCLUSIONS: Meantoinea alophosioides
enriches the documented moss diversity of an already-diverse Early Cretaceous
plant fossil assemblage. This is the third moss described from the Apple Bay
plant fossil assemblage and represents the first occurrence of gemma cups in a
fossil moss. It is also the oldest unequivocal record of Polytrichaceae,
providing a hard minimum age for the group of 136 million years.
PMID- 28424207
TI - A distributed solute model: an extended two-pore model with application to the
glomerular sieving of Ficoll.
AB - One of the many unresolved questions regarding the permeability of the glomerular
filtration barrier is the reason behind the marked difference in permeability
between albumin and polysaccharide probe molecules such as Ficoll and dextran of
the same molecular size. Although the differences in permeability have been
mainly attributed to charge effects, we have previously shown that this would
require a highly charged filtration barrier, having a charge density that is ~10
times more than that on the albumin molecule. In this article, the classic two
pore model was extended by introducing size distributions on the solute
molecules, making them conformationally flexible. Experimental sieving data for
Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes
were analyzed using the model. For the rat glomerulus a small-pore radius of 36.2
A and a geometric standard deviation (gSD) for the Ficoll size-distribution of
1.16 were obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore
radius of 43 A were found. Interestingly, a variation of only ~16% in the size of
the polysaccharide molecule is sufficient to explain the difference in
permeability between albumin and Ficoll. Also, in line with previous data, the
effects of applying a size distribution on the solute molecule are only evident
when the molecular size is close to the pore size. Surely there is at least some
variation in the pore radii, and, likely, the gSD obtained in the current study
is an overestimation of the "true" variation in the size of the Ficoll molecule.
PMID- 28424208
TI - Architecture of the rat nephron-arterial network: analysis with micro-computed
tomography.
AB - Among solid organs, the kidney's vascular network stands out, because each
nephron has two distinct capillary structures in series and because
tubuloglomerular feedback, one of the mechanisms responsible for blood flow
autoregulation, is specific to renal tubules. Tubuloglomerular feedback and the
myogenic mechanism, acting jointly, autoregulate single-nephron blood flow. Each
generates a self-sustained periodic oscillation and an oscillating electrical
signal that propagates upstream along arterioles. Similar electrical signals from
other nephrons interact, allowing nephron synchronization. Experimental
measurements show synchronization over fields of a few nephrons; simulations
based on a simplified network structure that could obscure complex interactions
predict more widespread synchronization. To permit more realistic simulations, we
made a cast of blood vessels in a rat kidney, performed micro-computed tomography
at 2.5-MUm resolution, and recorded three-dimensional coordinates of arteries,
afferent arterioles, and glomeruli. Nonterminal branches of arcuate arteries form
treelike structures requiring two to six bifurcations to reach terminal branches
at the tree tops. Terminal arterial structures were either paired branches at the
tops of the arterial trees, from which 52.6% of all afferent arterioles
originated, or unpaired arteries not at the tree tops, yielding the other 22.9%;
the other 24.5% originated directly from nonterminal arteries. Afferent
arterioles near the corticomedullary boundary were longer than those farther
away, suggesting that juxtamedullary nephrons have longer afferent arterioles.
The distance separating origins of pairs of afferent arterioles varied randomly.
The results suggest an irregular-network tree structure with vascular nodes,
where arteriolar activity and local blood pressure interact.
PMID- 28424209
TI - The sulfilimine cross-link of collagen IV contributes to kidney tubular basement
membrane stiffness.
AB - Basement membranes (BMs), a specialized form of extracellular matrix, underlie
nearly all cell layers and provide structural support for tissues and interact
with cell surface receptors to determine cell behavior. Both macromolecular
composition and stiffness of the BM influence cell-BM interactions. Collagen IV
is a major constituent of the BM that forms an extensively cross-linked
oligomeric network. Its deficiency leads to BM mechanical instability, as
observed with glomerular BM in Alport syndrome. These findings have led to the
hypothesis that collagen IV and its cross-links determine BM stiffness. A
sulfilimine bond (S = N) between a methionine sulfur and a lysine nitrogen cross
links collagen IV and is formed by the matrix enzyme peroxidasin. In peroxidasin
knockout mice with reduced collagen IV sulfilimine cross-links, we find a
reduction in renal tubular BM stiffness. Thus this work provides the first direct
experimental evidence that collagen IV sulfilimine cross-links contribute to BM
mechanical properties and provides a foundation for future work on the
relationship of BM mechanics to cell function in renal disease.
PMID- 28424210
TI - UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia
reperfusion injury.
AB - Uncoupling protein-2 (UCP2) plays critical roles in energy metabolism and cell
survival. Previous investigations showed that UCP2 regulated the production of
extracellular matrix and renal fibrosis. However, little is known about UCP2 in
acute kidney injury (AKI). Here, we used Ucp2 knockout mice to investigate the
role of UCP2 in an AKI model generated by renal ischemia-reperfusion (I/R)
injury. The Ucp2 global knockout mice were born and grew normally without kidney
histological abnormality or renal dysfunction. Compared with littermates,
deletion of Ucp2 exacerbated I/R-induced AKI whereas increase of UCP2 by
conjugated linoleic acid (CLA) attenuated I/R injury. Tubular cell apoptosis and
autophagy were induced by I/R. After injury, more tubular cell apoptosis and less
autophagy were identified in the kidneys of knockout mice compared with their
littermates, and less apoptosis and more autophagy were observed in mice fed with
CLA. In vitro rotenone, an inhibitor of electron transport chain complex I, was
applied to induce energy depletion in cultured tubular epithelial cells. As
expected, rotenone-recovery (R/R) treatment induced tubular cell apoptosis and
autophagy. UCP2 plasmid transfection reduced cell apoptosis and facilitated
autophagy after R/R treatment, whereas UCP2 small interfering RNA (siRNA)
transfection sensitized cell apoptosis but reduced autophagy induced by R/R
treatment. Interference of autophagy by treatment with autophagy inhibitor 3
methyladenine or autophagy initiation protein Beclin-1 siRNA transfection
resulted in tubular cell apoptosis. Thus UCP2 attenuates I/R-induced AKI,
probably by reducing cell apoptosis through protection of autophagy.
PMID- 28424211
TI - Connecting tubule glomerular feedback mediates tubuloglomerular feedback
resetting after unilateral nephrectomy.
AB - Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure
(PGC) that can cause significant glomerular injury in the remnant kidney. PGC is
controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance.
Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1)
tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to
increased NaCl in the macula densa; and 2) connecting tubule glomerular feedback
(CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport
in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of
TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and
cause renal damage, but the mechanism behind this resetting is unclear. Since
CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased
after UNx and contributes to TGF resetting. To test this hypothesis, we performed
UNx in Sprague-Dawley (8) rats. Twenty-four hours after surgery, we performed
micropuncture of individual nephrons and measured stop-flow pressure (PSF). PSF
is an indirect measurement of PGC. Maximal TGF response at 40 nl/min was 8.9 +/-
1.24 mmHg in sham-UNx rats and 1.39 +/- 1.02 mmHg in UNx rats, indicating TGF
resetting after UNx. When CTGF was inhibited with the ENaC blocker benzamil (1
MUM/l), the TGF response was 12.29 +/- 2.01 mmHg in UNx rats and 13.03 +/- 1.25
mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We
conclude that enhanced CTGF contributes to TGF resetting after UNx.
PMID- 28424213
TI - Magnesium improves cisplatin-mediated tumor killing while protecting against
cisplatin-induced nephrotoxicity.
AB - Approximately 30% of all cancer patients treated with cisplatin, a widely used
broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI).
Almost all patients receiving cisplatin have magnesium (Mg) losses, which are
proposed to aggravate AKI. Currently, there are no methods to successfully treat
or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI
in experimental models and several small clinical trials, the effects of Mg
status on tumor outcomes in immunocompetent tumor-bearing mice and humans have
not been investigated. The purpose of this study was to further examine the
effects of Mg deficiency (+/-Mg supplementation) on cisplatin-mediated AKI and
tumor killing in immunocompetent mice bearing CT26 colon tumors. Using a model
where cisplatin alone (20 mg/kg cumulative dose) produced minimal kidney injury,
Mg deficiency significantly worsened cisplatin-mediated AKI, as determined by
biochemical markers (blood urea nitrogen and plasma creatinine) and histological
renal changes, as well as markers of renal oxidative stress, inflammation, and
apoptosis. By contrast, Mg supplementation blocked cisplatin-induced kidney
injury. Using LLC-PK1 renal epithelial cells, we observed that Mg deficiency or
inhibition of Mg uptake significantly enhanced cisplatin-induced cytotoxicity,
whereas Mg supplementation protected against cytotoxicity. However, neither Mg
deficiency nor inhibition of Mg uptake impaired cisplatin-mediated killing of
CT26 tumor cells in vitro. Mg deficiency was associated with significantly larger
CT26 tumors in BALB/c mice when compared with normal-fed control mice, and Mg
deficiency significantly reduced cisplatin-mediated tumor killing in vivo.
Finally, Mg supplementation did not compromise cisplatin's anti-tumor efficacy in
vivo.
PMID- 28424212
TI - PDGF receptor-beta uses Akt/mTORC1 signaling node to promote high glucose-induced
renal proximal tubular cell collagen I (alpha2) expression.
AB - Increased expression of PDGF receptor-beta (PDGFRbeta) has been shown in renal
proximal tubules in mice with diabetes. The core molecular network used by high
glucose to induce proximal tubular epithelial cell collagen I (alpha2) expression
is poorly understood. We hypothesized that activation of PDGFRbeta by high
glucose increases collagen I (alpha2) production via the Akt/mTORC1 signaling
pathway in proximal tubular epithelial cells. Using biochemical and molecular
biological techniques, we investigated this hypothesis. We show that high glucose
increases activating phosphorylation of the PDGFRbeta, resulting in
phosphorylation of phosphatidylinositol 3-kinase. A specific inhibitor, JNJ
10198409, and small interfering RNAs targeting PDGFRbeta blocked this
phosphorylation without having any effect on MEK/Erk1/2 activation. We also found
that PDGFRbeta regulates high glucose-induced Akt activation, its targets tuberin
and PRAS40 phosphorylation, and finally, mTORC1 activation. Furthermore,
inhibition of PDGFRbeta suppressed high glucose-induced expression of collagen I
(alpha2) in proximal tubular cells. Importantly, expression of constitutively
active Akt or mTORC1 reversed these processes. As a mechanism, we found that JNJ
and PDGFRbeta knockdown inhibited high glucose-stimulated Hif1alpha expression.
Furthermore, overexpression of Hif1alpha restored expression of collagen I
(alpha2) that was inhibited by PDGFRbeta knockdown in high glucose-stimulated
cells. Finally, we show increased phosphorylation of PDGFRbeta and its
association with Akt/mTORC1 activation, Hif1alpha expression, and elevated
collagen I (alpha2) levels in the renal cortex of mice with diabetes. Our results
identify PDGFRbeta as a driver in activating Akt/mTORC1 nexus for high glucose
mediated expression of collagen I (alpha2) in proximal tubular epithelial cells,
which contributes to tubulointerstitial fibrosis in diabetic nephropathy.
PMID- 28424215
TI - Medical Marijuana Laws May Be Associated With A Decline In The Number Of
Prescriptions For Medicaid Enrollees.
AB - In the past twenty years, twenty-eight states and the District of Columbia have
passed some form of medical marijuana law. Using quarterly data on all fee-for
service Medicaid prescriptions in the period 2007-14, we tested the association
between those laws and the average number of prescriptions filled by Medicaid
beneficiaries. We found that the use of prescription drugs in fee-for-service
Medicaid was lower in states with medical marijuana laws than in states without
such laws in five of the nine broad clinical areas we studied. If all states had
had a medical marijuana law in 2014, we estimated that total savings for fee-for
service Medicaid could have been $1.01 billion. These results are similar to
those in a previous study we conducted, regarding the effects of medical
marijuana laws on the number of prescriptions within the Medicare population.
Together, the studies suggest that in states with such laws, Medicaid and
Medicare beneficiaries will fill fewer prescriptions.
PMID- 28424214
TI - Functional Conservation and Divergence among Homoeologs of TaSPL20 and TaSPL21,
Two SBP-Box Genes Governing Yield-Related Traits in Hexaploid Wheat.
AB - Maintaining high and stable yields has become an increasing challenge in wheat
breeding due to climate change. Although Squamosa-promoter binding protein (SBP)
box genes have important roles in plant development, very little is known about
the actual biological functions of wheat SBP-box family members. Here, we dissect
the functional conservation, divergence, and exploitation of homoeologs of two
paralogous TaSPL wheat loci during domestication and breeding. TaSPL20 and
TaSPL21 were highly expressed in the lemma and palea. Ectopic expressions of
TaSPL20/21 in rice exhibited similar functions in terms of promoting panicle
branching but had different functions during seed development. We characterized
all six TaSPL20/21 genes located across the three homoeologous (A, B, and D)
genomes. According to the functional analysis of naturally occurring variants in
20 environments, four favorable haplotypes were identified. Together, they
reduced plant height by up to 27.5%, and TaSPL21-6D-HapII increased 1000-grain
weight by 9.73%. Our study suggests that TaSPL20 and TaSPL21 homoeologs underwent
diversification in function with each evolving its own distinctive
characteristics. During domestication and breeding of wheat in China, favorable
haplotypes of each set were selected and exploited to varying degrees due to
their large effects on plant height and 1000-grain weight.
PMID- 28424216
TI - White coat.
PMID- 28424217
TI - Use of life jackets and other types of flotation for in-water recreation in
designated swim areas in Washington State.
AB - : Most fatal drownings worldwide occur in open water. Flotation devices may
protect swimmers. Their use by those recreating in water has not been described.
METHODS: Observational survey of swimmers and waders at designated swim sites at
lakes and rivers evaluated them by age group, sex, type of flotation used (life
jacket vs substandard flotation, eg, water wings, noodles, inflatables) and, for
children <6 years, being within arm's reach of an adult. RESULTS: Of 1967
swimmers/waders observed, 37% used some type of flotation device. Use rates,
especially of life jackets, decreased with increasing age. Children <6 years had
the highest use of some type of flotation (140/212, 66%) and the highest use of
life jackets (50.5%). Children <13 years were more likely to use flotation
devices and life jackets than teens (RR 6.78, 3.62 to 12.71); boys were more
likely than girls to wear life jackets (RR 1.47, 1.18 to 1.83). While teenagers
and adults used flotation (29.5% and 23.5%), they rarely used life jackets (2
3%). Boys <6 years who were further than arm's length of an adult were more
likely to wear life jackets than girls. Substandard flotation use did not differ
among age groups (15.5-26.5%) but their use was greater among females in most age
groups. CONCLUSIONS: Flotation devices were frequently used for recreational
wading and swimming in open water by all age groups. Life jacket use was limited
to children. Promoting use of flotation devices with safety standards that
provide protection as well as fun could potentially decrease open water drowning
rates.
PMID- 28424218
TI - GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in
C. elegans.
AB - Apoptotic cells generated by programmed cell death are engulfed by phagocytes and
enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes
involves a series of membrane-remodeling events that are governed by the
sequential actions of Rab GTPases and lead to formation of phagolysosomes, where
cell corpses are degraded. Here we identified gop-1 as a novel regulator of
apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects
phagosome maturation through the RAB-5-positive stage, causing defects in
phagosome acidification and phagolysosome formation, phenotypes identical to and
unaffected by loss of unc-108, the C. elegans Rab2 GOP-1 transiently associates
with cell corpse-containing phagosomes, and loss of its function abrogates
phagosomal association of UNC-108. GOP-1 interacts with GDP-bound and nucleotide
free UNC-108/Rab2, disrupts GDI-UNC-108 complexes, and promotes activation and
membrane recruitment of UNC-108/Rab2 in vitro. Loss of gop-1 also abolishes
association of UNC-108 with endosomes, causing defects in endosome and dense core
vesicle maturation. Thus, GOP-1 is an activator of UNC-108/Rab2 in multiple
processes.
PMID- 28424219
TI - Downregulation of RBO-PI4KIIIalpha Facilitates Abeta42 Secretion and Ameliorates
Neural Deficits in Abeta42-Expressing Drosophila.
AB - Phosphoinositides and their metabolizing enzymes are involved in Abeta42
metabolism and Alzheimer's disease pathogenesis. In yeast and mammals, Eighty
five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO),
forms a plasma membrane-localized protein complex with phosphatidylinositol-4
kinase Type IIIalpha (PI4KIIIalpha) and a scaffold protein to tightly control the
level of plasmalemmal phosphatidylinositol-4-phosphate (PI4P). Here, we report
that RBO binds to Drosophila PI4KIIIalpha, and that in an Abeta42-expressing
Drosophila model, separate genetic reduction of PI4KIIIalpha and RBO, or
pharmacological inhibition of PI4KIIIalpha ameliorated synaptic transmission
deficit, climbing ability decline, premature death, and reduced neuronal
accumulation of Abeta42 Moreover, we found that RBO-PI4KIIIa downregulation
increased neuronal Abeta42 release and that PI4P facilitated the assembly or
oligomerization of Abeta42 in/on liposomes. These results indicate that RBO
PI4KIIIa downregulation facilitates neuronal Abeta42 release and consequently
reduces neuronal Abeta42 accumulation likely via decreasing Abeta42 assembly
in/on plasma membrane. This study suggests the RBO-PI4KIIIalpha complex as a
potential therapeutic target and PI4KIIIalpha inhibitors as drug candidates for
Alzheimer's disease treatment.SIGNIFICANCE STATEMENT Phosphoinositides and their
metabolizing enzymes are involved in Abeta42 metabolism and Alzheimer's disease
pathogenesis. Here, in an Abeta42-expressing Drosophila model, we discovered and
studied the beneficial role of downregulating RBO or its interacting protein
PI4KIIIalpha-a protein that tightly controls the plasmalemmal level of PI4P
against the defects caused by Abeta42 expression. Mechanistically, RBO
PI4KIIIalpha downregulation reduced neuronal Abeta42 accumulation, and
interestingly increased neuronal Abeta42 release. This study suggests the RBO
PI4KIIIalpha complex as a novel therapeutic target, and PI4KIIIalpha inhibitors
as new drug candidates.
PMID- 28424220
TI - GABABR-Induced EGFR Transactivation Promotes Migration of Human Prostate Cancer
Cells.
AB - G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) act in
concert to regulate cell growth, proliferation, survival, and migration.
Metabotropic GABAB receptor (GABABR) is the GPCR for the main inhibitory
neurotransmitter GABA in the central nervous system. Increased expression of
GABABR has been detected in human cancer tissues and cancer cell lines, but the
role of GABABR in these cells is controversial and the underlying mechanism
remains poorly understood. Here, we investigated whether GABABR hijacks RTK
signaling to modulate the fates of human prostate cancer cells. RTK array
analysis revealed that the GABABR-specific agonist baclofen selectively induced
the transactivation of EGFR in PC-3 cells. EGFR transactivation resulted in the
activation of ERK1/2 by a mechanism that is dependent on Gi/o protein and that
requires matrix metalloproteinase-mediated proligand shedding. Positive
allosteric modulators (PAMs) of GABABR, such as CGP7930, rac-BHFF, and GS39783,
can function as PAM agonists to induce EGFR transactivation and subsequent ERK1/2
activation. Moreover, both baclofen and CGP7930 promoted cell migration and
invasion through EGFR signaling. In summary, our observations demonstrated that
GABABR transactivated EGFR in a ligand-dependent mechanism to promote prostate
cancer cell migration and invasion, thus providing new insights into developing a
novel strategy for prostate cancer treatment by targeting neurotransmitter
signaling.
PMID- 28424221
TI - Association Between Fetal Congenital Heart Defects and Maternal Risk of
Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies.
AB - BACKGROUND: Both pregnant women carrying fetuses with heart defects and women
with hypertensive disorders of pregnancy often exhibit angiogenic imbalances,
suggesting that the same mechanisms are involved in the pathogenesis of the
former and the pathophysiology of the latter. We conducted a register-based
cohort study to determine whether offspring congenital heart defects are
associated with an increased risk of hypertensive disorders of pregnancy and
whether the mechanisms driving any association are primarily maternal or fetal.
METHODS: Among singleton pregnancies without chromosomal abnormalities lasting
>=20 weeks in Denmark from 1978 to 2011 (n= 1 972 857), we identified pregnancies
complicated by offspring congenital heart defects or early preterm preeclampsia,
late preterm preeclampsia, term preeclampsia, and gestational hypertension. We
used polytomous logistic regression to estimate odds ratios (ORs) for
associations between offspring congenital heart defects and maternal hypertensive
disorders of pregnancy overall and for specific heart defects. RESULTS: Offspring
congenital heart defects were strongly associated with early preterm preeclampsia
(OR, 7.00; 95% confidence interval [CI], 6.11-8.03) and late preterm preeclampsia
(OR, 2.82; 95% CI, 2.38-3.34) in the same pregnancy and weakly associated with
term preeclampsia (OR, 1.16; 95% CI, 1.06-1.27), but they were not associated
with gestational hypertension (OR, 1.07; 95% CI, 0.92-1.25). Association
strengths were consistent across heart defect types. Offspring congenital heart
defects in a previous pregnancy were also strongly associated with preterm
preeclampsia in subsequent pregnancies (early preterm preeclampsia: OR, 2.37; 95%
CI, 1.68-3.34; late preterm preeclampsia: OR, 2.04; 95% CI, 1.52-2.75) but were
only modestly associated with term preeclampsia and not associated with
gestational hypertension. Similarly, preterm preeclampsia in a previous
pregnancy, but not term preeclampsia or gestational hypertension, was associated
with offspring congenital heart defects in later pregnancies (early preterm
preeclampsia: OR, 7.91; 95% CI, 6.06-10.3; late preterm preeclampsia: OR, 2.83;
95% CI, 2.11-3.79; term preeclampsia: OR, 0.98; 95% CI, 0.88-1.10; gestational
hypertension: OR, 1.13; 95% CI, 0.92-1.38). CONCLUSIONS: Linked
pathophysiological mechanisms may be involved in some congenital heart defects
and preterm preeclampsia. The strong associations across pregnancies support a
predominantly maternal origin of effect.
PMID- 28424222
TI - Randomized Comparison of Paclitaxel-Eluting Balloon and Stenting Versus Plain
Balloon Plus Stenting Versus Directional Atherectomy for Femoral Artery Disease
(ISAR-STATH).
AB - BACKGROUND: Atherosclerosis in the superficial femoral artery is common in
patients suffering from peripheral artery disease. Paclitaxel-eluting balloon
(PEB) angioplasty, stenting, and directional atherectomy (DA) have provided new
options for the treatment of superficial femoral artery disease; however, the
comparative efficacy of these interventional strategies remains uncertain.
METHODS: One hundred and fifty-five patients with symptomatic peripheral artery
disease due to de novo superficial femoral artery stenotic or occlusive lesions
were randomized to treatment with plain balloon angioplasty (BA) followed by PEB
angioplasty and stenting (n=48), BA and stenting (n=52), or DA with distal
protection and bailout stenting (n=55). The primary end point of the study was
percentage diameter stenosis after 6 months measured by angiography. Other end
points included target lesion revascularization, thrombosis, ipsilateral
amputation, binary restenosis, and all-cause mortality at 6 and 24 months.
RESULTS: Baseline and lesion characteristics were comparable in all groups with a
mean lesion length of 65.9+/-46.8 mm and 56% total occlusions. At 6 months
angiography, the percent diameter stenosis was significantly lower in patients
treated by PEB angioplasty and stenting (34+/-31%) as compared with BA
angioplasty and stenting (56+/-29%, P=0.009) or DA (55+/-29%, P=0.007).
Similarly, binary restenosis was significantly lower after treatment with PEB and
stenting as compared with BA and stenting or DA. Clinical follow-up at 24 months
revealed a lower risk for target lesion revascularization after PEB angioplasty
and stenting as compared with BA and stenting or DA. We found no difference in
terms of target lesion thrombosis and mortality among groups, and no patient
underwent amputation. CONCLUSIONS: Treatment of de novo superficial femoral
artery lesions with PEB angioplasty and stenting is superior to BA angioplasty
and stenting or DA in terms of angiographic diameter stenosis at 6 months and
target lesion revascularization at 24 months. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00986752.
PMID- 28424224
TI - Novel Strategies to Reduce Femoropopliteal Restenosis: Low-Dose Paclitaxel-Coated
Balloons and Paclitaxel-Coated Balloons Plus Stenting.
PMID- 28424223
TI - Low-Dose Paclitaxel-Coated Versus Uncoated Percutaneous Transluminal Balloon
Angioplasty for Femoropopliteal Peripheral Artery Disease: One-Year Results of
the ILLUMENATE European Randomized Clinical Trial (Randomized Trial of a Novel
Paclitaxel-Coated Percutaneous Angioplasty Balloon).
AB - BACKGROUND: Numerous studies have reported favorable outcomes using drug-coated
balloons (DCBs) for treatment of symptomatic peripheral artery disease of the
superficial femoral and popliteal arteries. However, the treatment effect
compared with an uncoated balloon has differed greatly among the randomized
trials, with better outcomes observed with higher-dose DCBs. This European trial
was designed to assess the safety and effectiveness of a next-generation low-dose
(2-ug/mm2 surface dose of paclitaxel) DCB. METHODS: This was a prospective,
randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to
treatment with a low-dose DCB or an uncoated percutaneous transluminal
angioplasty (PTA) balloon. The primary safety end point was a composite of
freedom from device- and procedure-related death through 30 days after the
procedure and freedom from target limb major amputation and clinically driven
target lesion revascularization through 12 months after the procedure. The
primary effectiveness end point was primary patency at 12 months. RESULTS:
Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or
uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation.
Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented
total occlusions, respectively. The primary safety end point was met, and
superiority was demonstrated; freedom from a primary safety event was 94.1% (193
of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95%
confidence interval, 0.9%-23.0%). The primary effectiveness end point was met,
and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40
of 66]; P<0.001). Outcomes with DCB were also superior to PTA per the Kaplan
Meier estimate for primary patency (89.0% versus 65.0% at 365 days; log-rank
P<0.001) and for rates of clinically driven target lesion revascularization (5.9%
versus 16.7%; P=0.014). CONCLUSIONS: Superiority with a low-dose DCB for
femoropopliteal interventions was demonstrated over PTA for both the safety and
effectiveness end points. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01858363.
PMID- 28424225
TI - Quantitative Assessment of Airway Pathology in Subjects With COPD Using Low-Dose
High-Resolution Computed Tomography.
AB - BACKGROUND: The purpose of this study was to correlate airway parameters of COPD
determined by low-dose high-resolution computed tomography (HRCT) with pulmonary
function testing (PFT) results. METHODS: PFT data were collected for subjects
with COPD and healthy controls. All subjects received inspiratory and expiratory
phase low-dose HRCT. Bronchi in the apical segment of the right upper lobe (RB1),
posterior segment of the right lower lobe (RB6), and lower lingual segment of the
left upper lobe (LB5) were the target bronchi. Software automatically calculated
airway wall area, inner area, and airway wall area percentage (percentage wall
area for bronchial external area). RESULTS: A total of 75 COPD and 20 control
subjects were included. The subjects with COPD were classified according to COPD
stage, with 20 grade I, II, and III subjects, respectively, and 15 grade IV
subjects. In COPD grade II, residual volume/total lung capacity was negatively
correlated with airway wall area in LB5 (r = -0.51). In COPD grade III, FVC was
negatively correlated with airway wall area percentage in LB5 (r = -0.49) but
positively correlated with airway wall area in RB6 (r = 0.52); percent-of
predicted FEV1 was negatively correlated with airway wall area percentage in RB1
(r = -0.49); residual volume was negatively correlated with airway wall area (r =
-0.47), and total lung capacity was negatively correlated with airway wall area
in RB1 (r = -0.52) (all, P < .001). CONCLUSIONS: The results of this study
suggest that airway parameters in different COPD grades have no uniform tendency
of correlation with PFT, but some HRCT parameters are correlated to some PFT
parameters.
PMID- 28424226
TI - Objective Measurement of Adherence to Out-Patient Airway Clearance Therapy by
High-Frequency Chest Wall Compression in Cystic Fibrosis.
AB - BACKGROUND: Objective measures of adherence to high-frequency chest wall
compression (HFCWC), a form of airway clearance therapy for patients with cystic
fibrosis, are lacking. We used a novel electronic monitoring device integrated
into an HFCWC vest to measure adherence compared with self-reported adherence. We
determined factors that influenced adherence and how adherence correlated with
baseline pulmonary function and pulmonary exacerbations. METHODS: Data were
collected by direct measurement of date, time of day, and duration of HFCWC use
to determine the number of daily treatments and daily duration of treatments.
Chart review provided prescribed airway clearance therapy treatment and
demographic and clinical information. Subject and caregiver report of the daily
number of airway clearance therapy treatments was obtained by telephone
interviews. Analysis used 2-sample and paired t test, analysis of variance, and
linear regression. RESULTS: Average adherence was 69%. Adherence was highest in
children (82%, P = .02) and those receiving assistance with treatment (82%, P <
.001). Subjects overestimated therapy duration from a mean +/- SD of 127 +/- 169%
by adults to 19.2 +/- 26.3% by parents or guardians of children. Average
adherence decreased with increasing prescribed therapy time (P = .02). Average
daily therapy time and adherence had significant positive associations with
baseline FEV1 percent of predicted (P = .02 and P = .02, respectively) and
negative associations with pulmonary exacerbations during the pre-study period
and at baseline (P = .044 and P = .02, respectively). CONCLUSIONS: Greater
adherence to HFCWC measured directly by a novel recorder was associated with
better baseline pulmonary function and fewer exacerbations in the pre-study and
baseline period. Adherence decreased with age and prescribed therapy time and
increased with therapy assistance. Self-report overestimation is large and thus
not an accurate measure of adherence.
PMID- 28424227
TI - ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple
Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.
AB - Breast cancer is a major cause of cancer-related death. TNF-related apoptosis
inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a
subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small
molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has
entered clinical trials in advanced cancers. Here, we show that ONC201 is
efficacious against both TNBC and non-TNBC cells (n = 13). A subset of TNBC and
non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines,
ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by
TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to
in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested
(6/8), ONC201 has an antiproliferative effect but does not induce apoptosis.
ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the
G1 phase of the cell cycle. pRb expression is associated with sensitivity to the
antiproliferative effects of ONC201, and the compound synergizes with taxanes in
less sensitive cells. All non-TNBC cells (n = 5) are growth inhibited following
ONC201 treatment, and unlike what has been observed with TRAIL, a subset (n = 2)
shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL
independent. Our data demonstrate that ONC201 has potent antiproliferative and
proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL
dependent and TRAIL-independent mechanisms. These findings develop a preclinical
rationale for developing ONC201 as a single agent and/or in combination with
approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. (c)2017
AACR.
PMID- 28424228
TI - Pseudomonas doesn't mind a dunking.
AB - A new study explains Pseudomonas aeruginosa's strong resistance to osmotic down
shock.
PMID- 28424230
TI - A quiet revolution in organ transplant ethics.
AB - A quiet revolution is occurring in the field of transplantation. Traditionally,
transplants have involved solid organs such as the kidney, heart and liver which
are transplanted to prevent recipients from dying. Now transplants are being done
of the face, hand, uterus, penis and larynx that aim at improving a recipient's
quality of life. The shift away from saving lives to seeking to make them better
requires a shift in the ethical thinking that has long formed the foundation of
organ transplantation. The addition of new forms of transplants requires doctors,
patients, regulators and the public to rethink the risk and benefit ratio
represented by trade-offs between saving life, extending life and risking the
loss of life to achieve improvements in the quality of life.
PMID- 28424229
TI - Tension-activated channels in the mechanism of osmotic fitness in Pseudomonas
aeruginosa.
AB - Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional
ability to adapt to a range of environments. Part of its adaptive potential is
the ability to survive drastic osmolarity changes. Upon a sudden dilution of
external medium, such as during exposure to rain, bacteria evade mechanical
rupture by engaging tension-activated channels that act as osmolyte release
valves. In this study, we compare fast osmotic permeability responses in
suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow
experiments and provide electrophysiological descriptions of osmotic-release
channels in PA. Using osmotic dilution experiments, we first show that PA
tolerates a broader range of shocks than EC. We record the kinetics of cell
equilibration reported by light scattering responses to osmotic up- and down
shocks. PA exhibits a lower water permeability and faster osmolyte release rates
during large osmotic dilutions than EC, which correlates with better survival. To
directly characterize the PA tension-activated channels, we generate giant
spheroplasts from this microorganism and record current responses in excised
patches. Unlike EC, which relies primarily on two types of channels, EcMscS and
EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a
more gradual response that is dominated by MscL-type channels. Genome analysis,
cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two
MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels
exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary
currents reveal that PaMscS-2 has a smaller conductance, higher anionic
preference, stronger inactivation, and slower recovery compared with PaMscS-1. We
conclude that PA relies on MscL as the major valve defining a high rate of
osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it
still requires MscS-type channels with a strong propensity to inactivation to
properly terminate massive permeability response.
PMID- 28424231
TI - Mroh1, a lysosomal regulator localized by WASH-generated actin.
AB - The steps leading to constitutive exocytosis are poorly understood. In
Dictyostelium WASH complex mutants, exocytosis is blocked, so cells that take up
fluorescent dextran from the medium retain it and remain fluorescent. Here, we
establish a FACS-based method to select cells that retain fluorescent dextran,
allowing identification of mutants with disrupted exocytosis. Screening a pool of
random mutants identified members of the WASH complex, as expected, and multiple
mutants in the conserved HEAT-repeat-containing protein Mroh1. In mroh1 mutants,
endosomes develop normally until the stage where lysosomes neutralize to
postlysosomes, but thereafter the WASH complex is recycled inefficiently, and
subsequent exocytosis is substantially delayed. Mroh1 protein localizes to
lysosomes in mammalian and Dictyostelium cells. In Dictyostelium, it accumulates
on lysosomes as they mature and is removed, together with the WASH complex,
shortly before the postlysosomes are exocytosed. WASH-generated F-actin is
required for correct subcellular localization; in WASH complex mutants, and
immediately after latrunculin treatment, Mroh1 relocalizes from the cytoplasm to
small vesicles. Thus, Mroh1 is involved in a late and hitherto undefined actin
dependent step in exocytosis.
PMID- 28424232
TI - Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during
Drosophila wound healing.
AB - Cell-cell fusion is widely observed during development and disease, and imposes a
dramatic change on participating cells. Cell fusion should be tightly controlled,
but the underlying mechanism is poorly understood. Here, we found that the
JAK/STAT pathway suppressed cell fusion during wound healing in the Drosophila
larval epidermis, restricting cell fusion to the vicinity of the wound. In the
absence of JAK/STAT signaling, a large syncytium containing a 3-fold higher
number of nuclei than observed in wild-type tissue formed in wounded epidermis.
The JAK/STAT ligand-encoding genes upd2 and upd3 were transcriptionally induced
by wounding, and were required for suppressing excess cell fusion. JNK (also
known as Basket in flies) was activated in the wound vicinity and activity peaked
at ~8 h after injury, whereas JAK/STAT signaling was activated in an adjoining
concentric ring and activity peaked at a later stage. Cell fusion occurred
primarily in the wound vicinity, where JAK/STAT activation was suppressed by
fusion-inducing JNK signaling. JAK/STAT signaling was both necessary and
sufficient for the induction of betaPS integrin (also known as Myospheroid)
expression, suggesting that the suppression of cell fusion was mediated at least
in part by integrin protein.
PMID- 28424233
TI - CLUH couples mitochondrial distribution to the energetic and metabolic status.
AB - Mitochondrial dynamics and distribution are critical for supplying ATP in
response to energy demand. CLUH is a protein involved in mitochondrial
distribution whose dysfunction leads to mitochondrial clustering, the metabolic
consequences of which remain unknown. To gain insight into the role of CLUH on
mitochondrial energy production and cellular metabolism, we have generated CLUH
knockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a
smaller cell size and with decreased abundance of respiratory complexes,
resulting in oxidative phosphorylation (OXPHOS) defects. This energetic
impairment was found to be due to the alteration of mitochondrial translation and
to a metabolic shift towards glucose dependency. Metabolomic profiling by mass
spectroscopy revealed an increase in the concentration of some amino acids,
indicating a dysfunctional Krebs cycle, and increased palmitoylcarnitine
concentration, indicating an alteration of fatty acid oxidation, and a dramatic
decrease in the concentrations of phosphatidylcholine and sphingomyeline,
consistent with the decreased cell size. Taken together, our study establishes a
clear function for CLUH in coupling mitochondrial distribution to the control of
cell energetic and metabolic status.
PMID- 28424234
TI - BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing
methods.
AB - AIMS: The assessment of B-raf proto-oncogene, serine/threonine kinase (BRAF) gene
status is now standard practice in patients diagnosed with metastatic melanoma
with its presence predicting a clinical response to treatment with BRAF
inhibitors. The gold standard in determining BRAF status is currently by DNA
based methods. More recently, a BRAF V600E antibody has been developed. We aim to
investigate whether immunohistochemical detection of BRAF mutation is a suitable
alternative to molecular testing by polymerase chain reaction (PCR). METHODS: We
assessed the incidence of BRAF mutation in our cohort of 132 patients, as
determined by PCR, as well as examining clinical and histopathological features.
We investigated the sensitivity and specificity of the anti-BRAF V600E VE1 clone
antibody in detecting the presence of the BRAF V600E mutation in 122 cases deemed
suitable for testing. RESULTS: The incidence of BRAF mutation in our cohort was
28.8% (38/132). Patients with the BRAF mutation were found to be significantly
younger at age of diagnosis. BRAF-mutated melanomas tended to be thinner and more
mitotically active. The antibody showed a sensitivity of 86.1% with a specificity
of 96.9%. The positive predictive value was 96.9%; the negative predictive value
was 94.4%. The concordance rate between PCR and immunohistochemical BRAF status
was 95.1% (116/122). CONCLUSIONS: The rate of BRAF mutation in our cohort (28.8%)
was lower than international published rates of 40%-60%. This may reflect ethnic
or geographic differences within population cohorts. The high concordance rate of
PCR and immunohistochemical methods in determining BRAF status suggests that
immunohistochemistry is potentially a viable, cost-effective alternative to PCR
testing and suitable as a screening test for the BRAF mutation.
PMID- 28424235
TI - Increased alloimmunisation and transfusion reaction reporting in patients with
solid-phase panreactivity.
AB - BACKGROUND: Automated solid-phase antibody screening uses red blood cell (RBC)
membranes immobilised on polystyrene test wells to detect RBC specific
antibodies. Despite its time-saving and labour-saving benefits, this method
produces a higher rate of nonspecific reactivity compared with manual screening.
Solid-phase panreactivity (SPP) is characterised by panreactivity (ie, all test
cells reacting) in solid-phase testing accompanied by a negative autocontrol and
a lack of reactivity when the same screening cells are tested in tube. The
mechanisms underlying SPP and its clinical significance remain unclear. The goals
of this study were to describe the prevalence of SPP at our institution and
determine the alloimmunisation and transfusion reaction rates within this
population. METHODS: Data were collected on all patients undergoing type and
screen testing over a 6-year period. Study patients undergoing subsequent
transfusion were evaluated for reported transfusion reactions and development of
new alloantibodies. RESULTS: Of the 76 051 patients studied, 0.7% demonstrated
SPP of which 11% developed new alloantibodies. The transfusion reaction reporting
rate among patients with SPP was 2%. CONCLUSIONS: Our data suggest that patients
with SPP have higher rates of reported transfusion reactions and alloantibody
development compared with those without SPP.
PMID- 28424236
TI - Hyalinizing trabecular tumour of the thyroid: fine-needle aspiration cytological
diagnosis and correlation with histology.
AB - Hyalinizing trabecular tumour (HTT) is a rare thyroid neoplasm of follicular cell
origin characterised by a trabecular growth pattern and prominent intratrabecular
and intertrabecular hyalinisation. These peculiar histological features allow the
prompt recognition of this neoplasm in surgical specimens. However, cytological
diagnosis of HTT remains elusive and misleading because of overlapping
characteristics with other thyroid tumours, particularly papillary thyroid
carcinoma (PTC), medullary thyroid carcinoma (MTC) and the newly described non
invasive follicular thyroid neoplasm with papillary-like nuclear features
(NIFTP). Nevertheless, the proper recognition of this neoplasm on preoperative
cytological preparations is important to avoid unnecessary overtreatment of this
indolent lesion. A thorough review of the literature has revealed that the
correct diagnosis of HTT in cytological smears is achieved in only 8% of cases.
In a further 6% of cases, diagnostic doubt has been indicated. Sixty percent of
published cases of HTT have been misdiagnosed as suggestive, suspicious or
positive for PTC. These findings underline the difficulties of a cytological
based diagnosis of such entity. In this article we review the cytomorphological
features of HTT and their correlation to histological features to provide the
reader with the tools to improve diagnostic performance in the identification of
HTT on preoperative cytology.
PMID- 28424237
TI - Absence of SMAD9v90m mutation in juvenile polyposis syndrome.
PMID- 28424238
TI - IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and
Function.
AB - Neutrophils possess multiple antimicrobial mechanisms that are critical for
protection of the host against infection with extracellular microbes, such as the
bacterial pathogen Staphylococcus aureus Recruitment and activation of
neutrophils at sites of infection are driven by cytokine and chemokine signals
that directly target neutrophils via specific cell surface receptors. The IL-20
subfamily of cytokines has been reported to act at epithelial sites and
contribute to psoriasis, wound healing, and anti-inflammatory effects during S.
aureus infection. However, the ability of these cytokines to directly affect
neutrophil function remains incompletely understood. In this article, we show
that human neutrophils altered their expression of IL-20R chains upon migration
and activation in vivo and in vitro. Such activation of neutrophils under
conditions mimicking infection with S. aureus conferred responsiveness to IL-20
that manifested as modification of actin polymerization and inhibition of a broad
range of actin-dependent functions, including phagocytosis, granule exocytosis,
and migration. Consistent with the previously described homeostatic and anti
inflammatory properties of IL-20 on epithelial cells, the current study provides
evidence that IL-20 directly targets and inhibits key inflammatory functions of
neutrophils during infection with S. aureus.
PMID- 28424239
TI - AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality.
AB - The absent in melanoma 2 (AIM2) inflammasome plays an important role in many
viral and bacterial infections, but very little is known about its role in RNA
virus infection, including influenza A virus (IAV). In this study, we have
designed in vivo and in vitro studies to determine the role of AIM2 in infections
with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV
infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase
1 activation and release of cleaved IL-1beta in the lung, which was significantly
reduced in AIM2-deficient mice. Interestingly, AIM2 deficiency did not affect the
transcription of caspase-1 and IL-1beta. In addition, AIM2-deficient mice
exhibited attenuated lung injury and significantly improved survival against IAV
challenges, but did not alter viral burden in the lung. However, AIM2 deficiency
did not seem to affect adaptive immune response against IAV infections.
Furthermore, experiments with AIM2-specific small interfering RNA-treated and
AIM2-deficient human and mouse lung alveolar macrophages and type II cells
indicated a macrophage-specific function of AIM2 in regulation of IAV-stimulated
proinflammatory response. Collectively, our results demonstrate that influenza
infection activates the AIM2 inflammasome, which plays a critical role in IAV
induced lung injury and mortality. AIM2 might serve as a therapeutic target for
combating influenza-associated morbidity and mortality without compromising the
host antiviral responses.
PMID- 28424240
TI - The Histone Acetyltransferase Gcn5 Positively Regulates T Cell Activation.
AB - Histone acetyltransferases (HATs) regulate inducible transcription in multiple
cellular processes and during inflammatory and immune response. However, the
functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily
conserved HAT from yeast to human, in immune regulation remain unappreciated. In
this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene)
specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and
demonstrated that Gcn5 plays important roles in multiple stages of T cell
functions including development, clonal expansion, and differentiation. Loss of
Gcn5 functions impaired T cell proliferation, IL-2 production, and Th1/Th17, but
not Th2 and regulatory T cell differentiation. Gcn5 is recruited onto the il-2
promoter by interacting with the NFAT in T cells upon TCR stimulation.
Interestingly, instead of directly acetylating NFAT, Gcn5 catalyzes histone H3
lysine H9 acetylation to promote IL-2 production. T cell-specific suppression of
Gcn5 partially protected mice from myelin oligodendrocyte glycoprotein-induced
experimental autoimmune encephalomyelitis, an experimental model for human
multiple sclerosis. Our study reveals previously unknown physiological functions
for Gcn5 and a molecular mechanism underlying these functions in regulating T
cell immunity. Hence Gcn5 may be an important new target for autoimmune disease
therapy.
PMID- 28424241
TI - Microbiota-Induced Antibodies Are Essential for Host Inflammatory Responsiveness
to Sterile and Infectious Stimuli.
AB - The indigenous intestinal microbiota is frequently considered an additional major
organ of the human body and exerts profound immunomodulating activities. Germ
free (GF) mice display a significantly different inflammatory responsiveness
pattern compared with conventional (CV) mice, and this was dubbed a
"hyporesponsive phenotype." Taking into account that the deposition of immune
complexes is a major event in acute inflammation and that GF mice have a distinct
Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig
repertoire interferes with the inflammatory responsiveness of GF mice. We found
that serum transfer from CV naive mice was capable of reversing the inflammatory
hyporesponsiveness of GF mice in sterile inflammatory injury induced by
intestinal ischemia and reperfusion, as well as in a model of lung infection by
Klebsiella pneumoniae Transferring serum from Ig-deficient mice to GF animals did
not alter their response to inflammatory insult; however, injecting purified Abs
from CV animals restored inflammatory responsiveness in GF mice, suggesting that
natural Abs present in serum were responsible for altering GF responsiveness.
Mechanistically, injection of serum and Ig from CV mice into GF animals restored
IgG deposition, leukocyte influx, NF-kappaB activation, and proinflammatory gene
expression in inflamed tissues and concomitantly downregulated annexin-1 and IL
10 production. Thus, our data show that microbiota-induced natural Abs are
pivotal for host inflammatory responsiveness to sterile and infectious insults.
PMID- 28424242
TI - mTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation.
AB - CD4+ T cells lacking the mTORC1 activator Rheb fail to secrete IFN-gamma under
Th1 polarizing conditions. We hypothesized that this phenotype is due to defects
in regulation of the canonical Th1 transcription factor T-bet at the level of
protein phosphorylation downstream of mTORC1. To test this hypothesis, we
employed targeted mass-spectrometry proteomic analysis-multiple reaction
monitoring mass spectrometry. We used this method to detect and quantify
predicted phosphopeptides derived from T-bet. By analyzing activated murine wild
type and Rheb-deficient CD4+ T cells, as well as murine CD4+ T cells activated in
the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to
identify six T-bet phosphorylation sites. Five of these are novel, and four sites
are consistently dephosphorylated in both Rheb-deficient CD4+ T cells and T cells
treated with rapamycin, suggesting mTORC1 signaling controls their
phosphorylation. Alanine mutagenesis of each of the six phosphorylation sites was
tested for the ability to impair IFN-gamma expression. Single phosphorylation
site mutants still support induction of IFN-gamma expression; however,
simultaneous mutation of three of the mTORC1-dependent sites results in
significantly reduced IFN-gamma expression. The reduced activity of the triple
mutant T-bet is associated with its failure to recruit chromatin remodeling
complexes to the Ifng gene promoter. These results establish a novel mechanism by
which mTORC1 regulates Th1 differentiation, through control of T-bet
phosphorylation.
PMID- 28424243
TI - Nutrition and High-Flow Nasal Cannula Respiratory Support in Children With
Bronchiolitis.
AB - OBJECTIVES: No guidelines are available regarding initiation of enteral nutrition
in children with bronchiolitis on high-flow nasal cannula (HFNC) support. We
hypothesized that the incidence of feeding-related adverse events (AEs) would not
be associated with HFNC support. METHODS: This retrospective study included
children <=24 months old with bronchiolitis receiving HFNC in a PICU from
September 2013 through April 2014. Data included demographics, respiratory
support during feeding, and feeding-related AEs. Feeding-related AEs were
extracted from nursing documentation and defined as respiratory distress or
emesis. Feed route and maximum HFNC delivery were recorded in 8-hour shifts (6 am
2 pm, 2 pm-10 pm, and 10 pm-6 am). RESULTS: 70 children were included, with a
median age of 5 (interquartile range [IQR] 2-10) months. HFNC delivery at feed
initiation varied widely, and AEs related to feeding occurred rarely. Children
were fed in 501 of 794 (63%) of nursing shifts, with AEs documented in only 29 of
501 (5.8%) of those shifts. The incidence of AEs at varying levels of respiratory
support did not differ (P = .092). Children in the "early feeding" (fed within
first 2 shifts) group (n = 22) had a shorter PICU length of stay (2.2 days [IQR
1.4-3.9] vs 3.2 [IQR 2.5-5.3], P = .006) and shorter duration of HFNC use (26.0
hours [IQR 15.8-57.0] vs 53.5 [IQR 37.0-84.8], P = .002), compared with children
in the "late feeding" group (n = 48). CONCLUSIONS: In this small, single
institution patient cohort, feeding-related AEs were rare and not related to the
delivered level of respiratory support.
PMID- 28424244
TI - Children With Bronchiolitis on High-Flow Nasal Cannula: To Feed or Not Feed, That
Is Not the Only Question.
PMID- 28424245
TI - Oral Nutrition in Children With Bronchiolitis on High-Flow Nasal Cannula Is Well
Tolerated.
AB - OBJECTIVES: To determine the incidence of aspiration-related respiratory failure
and nutrition interruptions in children with bronchiolitis on high-flow nasal
cannula (HFNC) receiving enteral nutrition. METHODS: We performed a single
center, prospective, observational cohort study within a 313-bed tertiary medical
center from January through December 2015. We included term children 1 month to 2
years of age without comorbid bacterial pneumonia or chronic medical conditions
who were diagnosed with bronchiolitis while receiving HFNC and enteral nutrition.
Primary outcomes were incidence of aspiration-related respiratory failure and
nutrition interruptions. Secondary outcomes were duration of HFNC therapy, length
of stay, and nutrition characteristics. RESULTS: Of the 344 children admitted
with bronchiolitis, 132 met the inclusion criteria. Ninety-seven percent received
enteral nutrition by mouth and 3% by nasogastric tube. HFNC flow rates at the
time of nutrition initiation ranged between 4 and 13 L per minute (0.3-1.9 L/kg
per minute) and respiratory rates from 18 to 69 breaths per minute. One (0.8%)
subject had aspiration-related respiratory failure and 12 (9.1%) experienced
nutrition interruptions. Children with interruptions in nutrition had a longer
length of stay by 2.5 days (P < .01) and received an additional day of HFNC
therapy (P < .01). By discharge, 55 (42%) children achieved all nutritional
goals: caloric, volume, and protein. Children admitted overnight had an increased
incidence of delay to nutrition initiation (30% vs 11%; P < .01). CONCLUSIONS: We
observed a low incidence of aspiration-related respiratory failure in term
children with bronchiolitis on HFNC receiving enteral nutrition. Oral nutrition
was tolerated across a range of HFNC flow and respiratory rates, suggesting the
practice of withholding nutrition in this population is unsupported.
PMID- 28424247
TI - Location in the spleen dictates the function of murine neutrophils.
AB - In this issue of JEM, Deniset et al. (https://doi.org/10.1084/jem.20161621)
provide new data that extend our knowledge on the mechanisms whereby
Streptococcus pneumoniae is cleared by the spleen. The authors identify novel
populations of murine splenic neutrophils that localize in the red pulp and the
marginal zone. During the acute phases of S. pneumoniae infection, these
populations of splenic neutrophils act in concert with specialized macrophage and
B cell populations to provide very rapid innate immune protection.
PMID- 28424246
TI - Enteropathy-associated T cell lymphoma subtypes are characterized by loss of
function of SETD2.
AB - Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common,
neoplastic complication of celiac disease. Here, we defined the genetic landscape
of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most
frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the
most frequently mutated pathway, with frequent mutations in STAT5B as well as
JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT
Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell
lymphoma) had highly overlapping genetic alterations indicating shared mechanisms
underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by
developing a T cell-specific knockout mouse. These mice manifested an expansion
of gammadelta T cells, indicating novel roles for SETD2 in T cell development and
lymphomagenesis. Our data render the most comprehensive genetic portrait yet of
this uncommon but lethal disease and may inform future classification schemes.
PMID- 28424248
TI - Splenic Ly6Ghigh mature and Ly6Gint immature neutrophils contribute to
eradication of S. pneumoniae.
AB - The spleen plays an integral protective role against encapsulated bacterial
infections. Our understanding of the associated mechanisms is limited to thymus
independent (TI) antibody production by the marginal zone (MZ) B cells, leaving
the contribution of other splenic compartments such as the red pulp (RP) largely
unexplored despite asplenic patients succumbing to the infection in the first 24
h, suggesting important antibody-independent mechanisms. In this study, using
time-lapse intravital imaging of the spleen, we identify a tropism for
Streptococcus pneumoniae in this organ mediated by tissue-resident MZ and RP
macrophages and a protective role for two distinct splenic neutrophil populations
(Ly6Ghi and Ly6Gintermediate) residing in the splenic RP. Splenic mature
neutrophils mediated pneumococcal clearance in the spleen by plucking bacteria
off the surface of RP macrophages that caught the majority of bacteria in a
complement-dependent manner. This neutrophil phagocytic capacity was further
enhanced after TI antibody production. Resident immature neutrophils
(Ly6Gintermediate) in the spleen undergo emergency proliferation and mobilization
from their splenic niche after pneumococcal stimulation to increase the effector
mature neutrophil pool. We demonstrate that splenic neutrophils together with two
macrophage populations and MZ B cells regulate systemic S. pneumoniae clearance
through complementary mechanisms.
PMID- 28424249
TI - Lignocellulose pretreatment in a fungus-cultivating termite.
AB - Depolymerizing lignin, the complex phenolic polymer fortifying plant cell walls,
is an essential but challenging starting point for the lignocellulosics
industries. The variety of ether- and carbon-carbon interunit linkages produced
via radical coupling during lignification limit chemical and biological
depolymerization efficiency. In an ancient fungus-cultivating termite system, we
reveal unprecedentedly rapid lignin depolymerization and degradation by combining
laboratory feeding experiments, lignocellulosic compositional measurements,
electron microscopy, 2D-NMR, and thermochemolysis. In a gut transit time of under
3.5 h, in young worker termites, poplar lignin sidechains are extensively cleaved
and the polymer is significantly depleted, leaving a residue almost completely
devoid of various condensed units that are traditionally recognized to be the
most recalcitrant. Subsequently, the fungus-comb microbiome preferentially uses
xylose and cleaves polysaccharides, thus facilitating final utilization of easily
digestible oligosaccharides by old worker termites. This complementary symbiotic
pretreatment process in the fungus-growing termite symbiosis reveals a previously
unappreciated natural system for efficient lignocellulose degradation.
PMID- 28424250
TI - Unifying mechanism for different fibrotic diseases.
AB - Fibrotic diseases are not well-understood. They represent a number of different
diseases that are characterized by the development of severe organ fibrosis
without any obvious cause, such as the devastating diseases idiopathic pulmonary
fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable
with endstage cancer and are uncurable. Given the phenotypic differences, it was
assumed that the different fibrotic diseases also have different pathomechanisms.
Here, we demonstrate that many endstage fibrotic diseases, including IPF;
scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and
nonalcoholic steatohepatosis converge in the activation of the AP1 transcription
factor c-JUN in the pathologic fibroblasts. Expression of the related AP1
transcription factor FRA2 was restricted to pulmonary artery hypertension.
Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple
organs and steatohepatosis, which was dependent on sustained c-Jun expression.
Single cell mass cytometry revealed that c-Jun activates multiple signaling
pathways in mice, including pAkt and CD47, which were also induced in human
disease. alphaCD47 antibody treatment and VEGF or PI3K inhibition reversed
various organ c-Jun-mediated fibroses in vivo. These data suggest that c-JUN is a
central molecular mediator of most fibrotic conditions.
PMID- 28424251
TI - Nuclear Shp2 directs normal embryo implantation via facilitating the ERalpha
tyrosine phosphorylation by the Src kinase.
AB - Estrogen and progesterone coupled with locally produced signaling molecules are
essential for embryo implantation. However, the hierarchical landscape of the
molecular pathways that governs this process remains largely unexplored. Here we
show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK
signaling, is predominately localized in the nuclei in the periimplantation mouse
uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor
(PR) expression and progesterone resistance, which derails normal uterine
receptivity, leading to complete implantation failure in mice. Notably, the PR
expression defects are attributed to the limited estrogen receptor alpha
(ERalpha) activation in uterine stroma. Further analysis reveals that nuclear
Shp2, rather than cytosolic Shp2, promotes the ERalpha transcription activity.
This function is achieved by enhancing the Src kinase-mediated ERalpha tyrosine
phosphorylation, which facilitates ERalpha binding to Pgr promoter in an ERK
independent manner in periimplantation uteri. Besides uncovering a regulatory
mechanism, this study could be clinically relevant to dysfunctional ERalpha
caused endometrial disorders in women.
PMID- 28424252
TI - Comparison of Saramis 4.12 and IVD 3.0 Vitek MS Matrix-Assisted Laser Desorption
Ionization-Time of Flight Mass Spectrometry for Identification of Mycobacteria
from Solid and Liquid Culture Media.
AB - During the last decade, many investigators have studied matrix-assisted laser
desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for
identification of mycobacteria. Diverse and contradictory results indicated that
optimal level for routine testing has not been reached yet. This work aimed to
assess Vitek MS through two distinct versions, Saramis v4.12 RUO and the IVD
v3.0, under conditions close to routine laboratory practice. Overall, 111
mycobacterial isolates were subjected to protein extraction and same spectra were
matched against both databases. The IVD v3.0 database proved to be superior to
Saramis v4.12 and its identification rates remarkably increased, from 67% to 94%
for isolates grown on Middlebrook 7H10 solid medium and from 62% to 91% for
isolates grown on mycobacterial growth indicator tube (MGIT) liquid medium. With
this new version, IVD v3.0, MALDI-TOF MS might be integrated into routine
clinical diagnostics, although molecular techniques remain mandatory in some
cases.
PMID- 28424253
TI - Identification of Acute HIV-1 Infection by Hologic Aptima HIV-1 RNA Qualitative
Assay.
AB - The Hologic Aptima HIV-1 Qualitative RNA assay was used in a rigorous screening
approach designed to identify individuals at the earliest stage of HIV-1
infection for enrollment into subsequent studies of cellular and viral events in
early infection (RV 217/Early Capture HIV Cohort [ECHO] study). Volunteers at
high risk for HIV-1 infection were recruited from study sites in Thailand,
Tanzania, Uganda, and Kenya with high HIV-1 prevalence rates among the
populations examined. Small-volume blood samples were collected by finger stick
at twice-weekly intervals and tested with the Aptima assay. Participants with
reactive Aptima test results were contacted immediately for entry into a more
comprehensive follow-up schedule with frequent blood draws. Evaluation of the
Aptima test prior to use in this study showed a detection sensitivity of 5.5
copies/ml (50%), with all major HIV-1 subtypes detected. A total of 54,306
specimens from 1,112 volunteers were examined during the initial study period
(August 2009 to November 2010); 27 individuals were identified as converting from
uninfected to infected status. A sporadic reactive Aptima signal was observed in
HIV-1-infected individuals under antiretroviral therapy. Occasional false
reactive Aptima results in uninfected individuals, or nonreactive results in HIV
1-infected individuals not on therapy, were observed and used to calculate assay
sensitivity and specificity. The sensitivity and specificity of the Aptima assay
were 99.03% and 99.23%, respectively; positive and negative predictive values
were 92.01% and 99.91%, respectively. Conversion from HIV-1-uninfected to
infected status was rapid, with no evidence of a prolonged period of intermittent
low-level viremia.
PMID- 28424254
TI - European Multicenter Study on Analytical Performance of Veris HIV-1 Assay.
AB - The analytical performance of the Veris HIV-1 assay for use on the new, fully
automated Beckman Coulter DxN Veris molecular diagnostics system was evaluated at
10 European virology laboratories. The precision, analytical sensitivity,
performance with negative samples, linearity, and performance with HIV-1
groups/subtypes were evaluated. The precision for the 1-ml assay showed a
standard deviation (SD) of 0.14 log10 copies/ml or less and a coefficient of
variation (CV) of <=6.1% for each level tested. The 0.175-ml assay showed an SD
of 0.17 log10 copies/ml or less and a CV of <=5.2% for each level tested. The
analytical sensitivities determined by probit analysis were 19.3 copies/ml for
the 1-ml assay and 126 copies/ml for the 0.175-ml assay. The performance with
1,357 negative samples demonstrated 99.2% with not detected results. Linearity
using patient samples was shown from 1.54 to 6.93 log10 copies/ml. The assay
performed well, detecting and showing linearity with all HIV-1 genotypes tested.
The Veris HIV-1 assay demonstrated analytical performance comparable to that of
currently marketed HIV-1 assays. (DxN Veris products are Conformite Europeenne
[CE]-marked in vitro diagnostic products. The DxN Veris product line has not been
submitted to the U.S. FDA and is not available in the U.S. market. The DxN Veris
molecular diagnostics system is also known as the Veris MDx molecular diagnostics
system and the Veris MDx system.).
PMID- 28424255
TI - Analysis of Milk from Mothers Who Delivered Prematurely Reveals Few Changes in
Proteases and Protease Inhibitors across Gestational Age at Birth and Infant
Postnatal Age.
AB - Background: Peptidomics research has demonstrated that protease activity is
higher in breast milk from preterm-delivering mothers than from term-delivering
mothers. However, to our knowledge, the effect of the degree of prematurity and
postnatal age on proteases and protease inhibitors in human milk remains
unknown.Objective: We aimed to determine the change of proteases and protease
inhibitors in milk from mothers who delivered prematurely across gestational age
(GA) and postnatal age.Methods: Milk samples were collected from 18 mothers aged
26-40 y who delivered preterm infants and who lacked mastitis. For analysis,
samples were separated into 2 groups: 9 from early GA (EGA) (24-26 wk GA)
delivering mothers and 9 from late GA (LGA) (27-32 wk GA)-delivering mothers.
Within the 9 samples in each group, the collection time ranged from postnatal
days 2 to 47. The activity and predicted activity of proteases in preterm milk
were determined with the use of fluorometric and spectrophotometric assays and
peptidomics, respectively. Protease and protease inhibitor concentrations were
determined with the use of ELISA. Linear mixed models were applied to compare
enzymes across GA and postnatal age.Results: Carboxypeptidase B2, kallikrein,
plasmin, elastase, thrombin, and cytosol aminopeptidase were present and active
in the milk of preterm-delivering mothers. Most milk protease and antiprotease
concentrations did not change with GA or postnatal age. However, the
concentration and activity of kallikrein, the most abundant and active protease
in preterm milk, increased by 25.4 ng . mL-1 . d-1 and 0.454 MUg . mL-1 . d-1
postnatally, respectively, in EGA milk samples while remaining stable in LGA milk
samples.Conclusions: This research demonstrates that proteases are active in
human milk and begin to degrade milk protein within the mammary gland before
consumption by infants. Proteases and protease inhibitors in milk from mothers of
premature infants mostly did not vary substantially across GA and postnatal age.
PMID- 28424256
TI - Dietary Patterns and Type 2 Diabetes: A Systematic Literature Review and Meta
Analysis of Prospective Studies.
AB - Background: Different methodologic approaches for constructing dietary patterns
and differences in their composition limit conclusions on healthful patterns for
diabetes prevention.Objective: We summarized evidence from prospective studies
that examined associations of dietary patterns with type 2 diabetes by
considering different methodologic approaches.Methods: The literature search
(MEDLINE and Web of Science) identified prospective studies (cohorts or trials)
that associated dietary patterns with diabetes incidence in nondiabetic and
apparently healthy participants. We summarized evidence by meta-analyses and
distinguished different methodologic approaches.Results: The search resulted in
48 articles comprising 16 cohorts. Adherence to the Mediterranean diet (RR for
comparing extreme quantiles: 0.87; 95% CI: 0.82, 0.93), Dietary Approaches to
Stop Hypertension (DASH) (RR: 0.81; 95% CI: 0.72, 0.92), and Alternative Healthy
Eating Index (AHEI) (RR: 0.79; 95% CI: 0.69, 0.90) was associated with
significant risk reductions of incident diabetes. Patterns from exploratory
factor and principal component analyses characterized by red and processed meat,
refined grains, high-fat dairy, eggs, and fried products ("mainly unhealthy")
were positively associated with diabetes (RR: 1.44; 95% CI: 1.27, 1.62), whereas
patterns characterized by vegetables, legumes, fruits, poultry, and fish ("mainly
healthy") were inversely associated with diabetes (RR: 0.84; 95% CI: 0.77, 0.91).
Reduced rank regression (RRR) used diabetes-related biomarkers to identify
patterns. These patterns were characterized by high intakes of refined grains,
sugar-sweetened soft drinks, and processed meat and were all significantly
associated with diabetes risk.Conclusions: Our meta-analysis suggests that diets
according to the Mediterranean diet, DASH, and AHEI have a strong potential for
preventing diabetes, although they differ in some particular components.
Exploratory dietary patterns were grouped based on concordant food groups and
were significantly associated with diabetes risk despite single-component foods
having limited evidence for an association. Still, they remain population
specific observations. Consistent positive associations with diabetes risk were
observed for 3 RRR patterns.
PMID- 28424257
TI - An Animal-Source Food Supplement Increases Micronutrient Intakes and Iron Status
among Reproductive-Age Women in Rural Vietnam.
AB - Background: Few studies have examined the impact of local animal-source foods
(ASFs) on the nutritional status of reproductive-age women in developing
countries.Objective: We hypothesized that a midmorning snack of local ASF for 6
mo would reduce dietary micronutrient deficiencies [usual intake less than the
estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc,
and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural
Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned
to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 MUg retinoic
acid equivalent vitamin A, and 5.5 MUg vitamin B-12) or a control snack (mean:
150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 MUg retinoic acid equivalent vitamin A, and 0
MUg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by
repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and
6 mo. Because of the relation between nutritional status and inflammation, serum
C-reactive protein, alpha-1-acid-glycoprotein, and urinary tract infections
(UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42
controls) completed the study. In the ASF group, intakes of iron and vitamins A
and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake
was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a
modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF
group compared with the control group, but plasma zinc, retinol, and serum
vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05)
among women assigned to the ASF group who had a low whole-body iron status at
baseline.Conclusions: Adding a small amount of locally produced ASF to the diets
of reproductive-age Vietnamese women improved micronutrient intakes and iron
status. However, the increased UTI incidence in women in the ASF group with
initially lower iron stores warrants further investigation.
PMID- 28424258
TI - Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron
Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.
AB - Background: Antenatal anemia is a risk factor for adverse maternal and fetal
outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal
anemia is considered responsive to iron; identifying women in need of iron may
help target interventions. Iron absorption is governed by the iron-regulatory
hormone hepcidin.Objective: We sought to characterize changes in hepcidin and its
associations with indexes of iron stores, erythropoiesis, and inflammation at
weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential
as an index of iron deficiency.Methods: We measured hemoglobin and serum
hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein
(CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women
recruited to a randomized controlled trial. Associations with hepcidin were
measured by using linear regression, and hepcidin's diagnostic test accuracy
[area under the receiver operating characteristic curve (AUCROC), sensitivity,
specificity, cutoffs] for iron deficiency at each time point was
analyzed.Results: The prevalence of anemia increased from 34.6% at 14 wk of
gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study
enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of
gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP
declined over pregnancy. The AUCROC values for hepcidin to detect iron deficiency
(defined as ferritin <15 MUg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk,
respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of
iron deficiency.Conclusions: In Gambian pregnant women, hepcidin appears to be a
useful diagnostic test for iron deficiency and may enable the identification of
cases for whom iron would be beneficial. Hepcidin suppression in the second
trimester suggests a window for optimal timing for antenatal iron interventions.
Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial
was registered at www.isrctn.com as ISRCTN49285450.
PMID- 28424259
TI - Maternal Vitamin D Insufficiency Early in Pregnancy Is Associated with Increased
Risk of Preterm Birth in Ethnic Minority Women in Canada.
AB - Background: Maternal vitamin D insufficiency (plasma 25-hydroxyvitamin D
[25(OH)D] <75 nmol/L) may play a role in ethnic disparities in rates of preterm
and spontaneous preterm births.Objective: We explored the relation between
maternal plasma 25(OH)D concentration in the first trimester (8-14 wk of
gestation) and the risk of preterm and spontaneous preterm births (<37 wk of
gestation) by ethnicity.Methods: We designed a case-control study that included
120 cases of preterm birth (<37 wk of gestation) and 360 term controls (>=37 wk
of gestation) of singleton pregnancies from the 3D cohort, a multicenter study in
2456 pregnant women in Quebec, Canada. Plasma 25(OH)D was measured by LC-mass
spectrometry. We compared the distribution of vitamin D status between cases and
controls for 8 ethnic minority subgroups. We explored the association between
maternal plasma 25(OH)D concentration and preterm and spontaneous preterm births
with the use of splines in logistic regression by ethnicity.Results: The
distributions of maternal vitamin D status (<50, 50-75, and >75 nmol/L) were
different in preterm and spontaneous preterm birth cases compared with controls
but only in women of ethnic minority (P-trend = 0.003 and 0.024, respectively).
Among ethnic subgroups, sub-Saharan Africans (P-trend = 0.030) and Arab-West
Asians (P-trend = 0.045) showed an inverse relation between maternal vitamin D
status and the risk of preterm birth. Maternal plasma 25(OH)D concentrations of
30 nmol/L were associated with 4.05 times the risk of preterm birth in the total
ethnic minority population (95% CI: 1.16, 14.12; P = 0.028) relative to
participants with a concentration of 75 nmol/L. In contrast, there was no such
association among nonethnic women (OR: 0.94; 95% CI: 0.48, 1.82; P = 0.85). There
was no association when we considered only spontaneous preterm births in the
total ethnic minority population (OR: 1.75; 95% CI: 0.39, 7.79; P =
0.46).Conclusion: Vitamin D insufficiency is associated with an increased risk of
preterm birth in ethnic minority women in Canada.
PMID- 28424260
TI - Upregulation of Zinc Absorption Matches Increases in Physiologic Requirements for
Zinc in Women Consuming High- or Moderate-Phytate Diets during Late Pregnancy and
Early Lactation.
AB - Background: Estimated physiologic requirements (PRs) for zinc increase in late
pregnancy and early lactation, but the effect on dietary zinc requirements is
uncertain.Objective: The aim of this study was to determine changes in daily
fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of
differing phytate contents in relation to physiologic zinc requirements during
pregnancy and lactation.Methods: This was a prospective observational study of
zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3)
and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of
childbearing age whose major food staple was maize and who had been randomly
assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate
maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary
zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined
from duplicate diets and fractional absorption (FAZ) by dual isotope ratio
technique (TAZ = TDZ * FAZ). All variables were examined longitudinally and by
group and compared with PRs. TAZ values at later phases were compared with phase
1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating
(NPNL) women.Results: TAZ was greater in the LP group than in the C group at all
phases. All variables increased from phase 1 to phases 2 and 3 and declined at
phase 4. TAZ increased by 1.25 mg/d (P = 0.045) in the C group and by 0.81 mg/d
(P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d
(P = 0.002) in the C group and 2.28 mg/d (P = 0.0004) in the LP group, compared
with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values
in phases 2-4.Conclusions: Upregulation of zinc absorption in late pregnancy and
early lactation matches increases in PRs of pregnant and lactating women,
regardless of dietary phytate, which has implications for dietary zinc
requirements of pregnant and lactating women.
PMID- 28424261
TI - Zinc Absorption from Milk Is Affected by Dilution but Not by Thermal Processing,
and Milk Enhances Absorption of Zinc from High-Phytate Rice in Young Dutch Women.
AB - Background: Milk has been suggested to increase zinc absorption. The effect of
processing and the ability of milk to enhance zinc absorption from other foods
has not been measured directly in humans.Objective: We aimed to assess zinc
absorption from 1) milk undergoing various processing and preparatory steps and
2) from intrinsically labeled high-phytate rice consumed with milk or
water.Methods: Two randomized crossover studies were conducted in healthy young
women [age:18-25 y; body mass index (in kg/m2): 20-25]: 1) a milk study (n = 19)
comparing the consumption of 800 mL full-fat ultra-high temperature (UHT) milk
[heat-treated milk (HTM)], full-fat UHT milk diluted 1:1 with water [heat-treated
milk and water (MW)], water, or unprocessed (raw) milk (UM), each extrinsically
labeled with 67Zn, and 2) a rice study (n = 18) comparing the consumption of 90 g
intrinsically 67Zn-labeled rice with 600 mL of water [rice and water (RW)] or
full-fat UHT milk [rice and milk (RM)]. The fractional absorption of zinc (FAZ)
was measured with the double-isotope tracer ratio method. In vitro, we assessed
zinc extraction from rice blended into water, UM, or HTM with or without
phytate.Results: FAZ from HTM was 25.5% (95% CI: 21.6%, 29.4%) and was not
different from UM (27.8%; 95% CI: 24.2%, 31.4%). FAZ from water was higher
(72.3%; 95% CI: 68.7%, 75.9%), whereas FAZ from MW was lower (19.7%; 95% CI:
17.5%, 21.9%) than HTM and UM (both P < 0.01). FAZ from RM (20.7%; 95% CI: 18.8%,
22.7%) was significantly higher than from RW (12.8%; 95% CI: 10.8%, 14.6%; P <
0.01). In vitro, HTM and UM showed several orders of magnitude higher extraction
of zinc from rice with HTM than from rice with water at various phytate
concentrations.Conclusions: Milk enhanced human FAZ from high-phytate rice by 62%
compared with water. Diluting milk with water decreases its absorption-enhancing
proprieties, whereas UHT processing does not. This trial was registered at the
Dutch trial registry as NTR4267
(http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4267).
PMID- 28424262
TI - Magnesium Reduces Hepatic Lipid Accumulation in Yellow Catfish (Pelteobagrus
fulvidraco) and Modulates Lipogenesis and Lipolysis via PPARA, JAK-STAT, and AMPK
Pathways in Hepatocytes.
AB - Background: Magnesium influences hepatic lipid deposition in vertebrates, but the
underlying mechanism is unknown.Objective: We used yellow catfish and their
isolated hepatocytes to test the hypothesis that magnesium influences lipid
deposition by modulating lipogenesis and lipolysis.Methods: Juvenile yellow
catfish (mean +/- SEM weight: 3.43 +/- 0.02 g, 3 mo old, mixed sex) were fed a
0.14- (low), 0.87- (intermediate) or 2.11- (high) g Mg/kg diet for 56 d. Primary
hepatocytes were incubated for 48 h in control or MgSO4-containing medium with or
without 2-h pretreatment with an inhibitor (AG490, GW6471, or Compound C). Growth
performance, cell viability, triglyceride (TG) concentrations, and expression of
enzymes and genes involved in lipid metabolism were measured. Results: Compared
with fish fed low magnesium, those fed intermediate or high magnesium had lower
hepatic lipids (18%, 22%) and 6-phosphogluconate dehydrogenase (6PGD; 3.7%, 3.8%)
and malic enzyme (ME; 35%, 48%) activities and greater mRNA levels of the
lipolytic genes adipose triacylglyceride lipase (atgl; 82% and 1.7-fold) and
peroxisome proliferator-activated receptor (ppara; 18% and 1.0-fold),
respectively (P < 0.05). Relative mRNA levels of AMP-activated protein kinase
(ampk) a1, ampka2, ampkb1, ampkb2, ampkg1a, ampkg1b, Janus kinase (jak) 2a,
jak2b, and signal transducers and activators of transcription (stat) 3 in fish
fed high magnesium were higher (24% to 3.1-fold, P < 0.05) than in those fed low
or intermediate magnesium. Compared with cells incubated with MgSO4 alone, those
incubated with MgSO4 and pretreated with AG490, GW6471, or Compound C had greater
TG concentrations (42%, 31%, or 56%), g6pd (98%, 59%, or 51%), 6pgd (68%, 73%, or
32%) mRNA expression, and activities of G6PD (35%, 45%, or 16%) and ME (1.5-fold,
1.3-fold, or 13%), and reduced upregulation (61%, 25%, or 45%) of the lipolytic
gene, atgl (P < 0.05).Conclusions: Magnesium reduced hepatic lipid accumulation
in yellow catfish and the variation might be attributed to inhibited lipogenesis
and increased lipolysis. PPARA, JAK-STAT, and AMPK pathways mediated the
magnesium-induced changes in lipid deposition and metabolism. These results offer
new insight into magnesium nutrition in vertebrates.
PMID- 28424263
TI - The kielin/chordin-like protein (KCP) attenuates high-fat diet-induced obesity
and metabolic syndrome in mice.
AB - Obesity and its associated complications such as insulin resistance and non
alcoholic fatty liver disease are reaching epidemic proportions. In mice, the TGF
beta superfamily is implicated in the regulation of white and brown adipose
tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted
regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and
activin signals while enhancing bone morphogenetic protein (BMP) signaling.
However, KCP's effects on metabolism and obesity have not been studied in animal
models. Therefore, we examined the effects of KCP loss or gain of function in
mice that were maintained on either a regular or a high-fat diet. KCP loss
sensitized the mice to obesity and associated complications such as glucose
intolerance and adipose tissue inflammation and fibrosis. In contrast, transgenic
mice that expressed KCP in the kidney, liver, and adipose tissues were resistant
to developing high-fat diet-induced obesity and had significantly reduced white
adipose tissue. Moreover, KCP overexpression shifted the pattern of SMAD
signaling in vivo, increasing the levels of phospho (P)-SMAD1 and decreasing P
SMAD3. Adipocytes in culture showed a cell-autonomous effect in response to added
TGF-beta1 or BMP7. Metabolic profiling indicated increased energy expenditure in
KCP-overexpressing mice and reduced expenditure in the KCP mutants with no effect
on food intake or activity. These findings demonstrate that shifting the TGF-beta
superfamily signaling with a secreted protein can alter the physiology and
thermogenic properties of adipose tissue to reduce obesity even when mice are fed
a high-fat diet.
PMID- 28424264
TI - Identification of a multienzyme complex for glucose metabolism in living cells.
AB - Sequential metabolic enzymes in glucose metabolism have long been hypothesized to
form multienzyme complexes that regulate glucose flux in living cells. However,
it has been challenging to directly observe these complexes and their functional
roles in living systems. In this work, we have used wide-field and confocal
fluorescence microscopy to investigate the spatial organization of metabolic
enzymes participating in glucose metabolism in human cells. We provide compelling
evidence that human liver-type phosphofructokinase 1 (PFKL), which catalyzes a
bottleneck step of glycolysis, forms various sizes of cytoplasmic clusters in
human cancer cells, independent of protein expression levels and of the choice of
fluorescent tags. We also report that these PFKL clusters colocalize with other
rate-limiting enzymes in both glycolysis and gluconeogenesis, supporting the
formation of multienzyme complexes. Subsequent biophysical characterizations with
fluorescence recovery after photobleaching and FRET corroborate the formation of
multienzyme metabolic complexes in living cells, which appears to be controlled
by post-translational acetylation on PFKL. Importantly, quantitative high-content
imaging assays indicated that the direction of glucose flux between glycolysis,
the pentose phosphate pathway, and serine biosynthesis seems to be spatially
regulated by the multienzyme complexes in a cluster-size-dependent manner.
Collectively, our results reveal a functionally relevant, multienzyme metabolic
complex for glucose metabolism in living human cells.
PMID- 28424265
TI - Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell
surface interactions.
AB - GNE (UDP-GlcNAc 2-epimerase/ManNAc kinase) myopathy is a rare muscle disorder
associated with aging and is related to sporadic inclusion body myositis, the
most common acquired muscle disease of aging. Although the cause of sporadic
inclusion body myositis is unknown, GNE myopathy is associated with mutations in
GNE. GNE harbors two enzymatic activities required for biosynthesis of sialic
acid in mammalian cells. Mutations to both GNE domains are linked to GNE
myopathy. However, correlation between mutation-associated reductions in sialic
acid production and disease severity is imperfect. To investigate other potential
effects of GNE mutations, we compared sialic acid production in cell lines
expressing wild type or mutant forms of GNE. Although we did not detect any
differences attributable to disease-associated mutations, lectin binding and mass
spectrometry analysis revealed that GNE deficiency is associated with
unanticipated effects on the structure of cell-surface glycans. In addition to
exhibiting low levels of sialylation, GNE-deficient cells produced distinct N
linked glycan structures with increased branching and extended poly-N
acetyllactosamine. GNE deficiency may affect levels of UDP-GlcNAc, a key
metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this
modest effect did not fully account for the change in N-linked glycan structure.
Furthermore, GNE deficiency and glucose supplementation acted independently and
additively to increase N-linked glycan branching. Notably, N-linked glycans
produced by GNE-deficient cells displayed enhanced binding to galectin-1,
indicating that changes in GNE activity can alter affinity of cell-surface
glycoproteins for the galectin lattice. These findings suggest an unanticipated
mechanism by which GNE activity might affect signaling through cell-surface
receptors.
PMID- 28424266
TI - Disease-associated extracellular loop mutations in the adhesion G protein-coupled
receptor G1 (ADGRG1; GPR56) differentially regulate downstream signaling.
AB - Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as
GPR56) underlie the neurological disorder bilateral frontoparietal
polymicrogyria. Disease-associated mutations in G1 studied to date are believed
to induce complete loss of receptor function through disruption of either
receptor trafficking or signaling activity. Given that N-terminal truncation of
G1 and other adhesion G protein-coupled receptors has been shown to significantly
increase the receptors' constitutive signaling, we examined two different
bilateral frontoparietal polymicrogyria-inducing extracellular loop mutations
(R565W and L640R) in the context of both full-length and N-terminally truncated
(DeltaNT) G1. Interestingly, we found that these mutations reduced surface
expression of full-length G1 but not G1-DeltaNT in HEK-293 cells. Moreover, the
mutations ablated receptor-mediated activation of serum response factor
luciferase, a classic measure of Galpha12/13-mediated signaling, but had no
effect on G1-mediated signaling to nuclear factor of activated T cells (NFAT)
luciferase. Given these differential signaling results, we sought to further
elucidate the pathway by which G1 can activate NFAT luciferase. We found no
evidence that DeltaNT activation of NFAT is dependent on Galphaq/11-mediated or
beta-arrestin-mediated signaling but rather involves liberation of Gbetagamma
subunits and activation of calcium channels. These findings reveal that disease
associated mutations to the extracellular loops of G1 differentially alter
receptor trafficking, depending on the presence of the N terminus, and
differentially alter signaling to distinct downstream pathways.
PMID- 28424267
TI - Using a novel data resource to explore heart rate during mountain and road
running.
AB - Online, accessible performance and heart rate data from running competitions are
posted publicly or semi-publicly to social media. We tested the efficacy of one
such data resource- Strava- as a tool in exercise physiology investigations by
exploring heart rate differences in mountain racing and road racing running
events. Heart rate and GPS pace data were gathered from Strava activities posted
by 111 males aged 21-49, from two mountain races (Mt. Washington Road Race and
Pike's Peak Ascent) and two road race distances (half marathon and marathon).
Variables of interest included race finish time, average heart rate, time to
complete the first half (by distance) of the race, time to complete the second
half, average heart rate for both the first and second half, estimated maximal
heart rate, and competitiveness (finish time as percentage of winning time).
Mountain runners on average showed no change in heart rate in the second versus
first half of the event, while road racers at the half marathon and marathon
distances showed increased second-half heart rate. Mountain runners slowed
considerably more in the second half than road runners. Heart rate increases in
road races were likely reflective of cardiac drift. Altitude and other demands
specific to mountain racing may explain why this was not observed in mountain
races. Strava presents enormous untapped opportunity for exercise physiology
research, enabling initial inquiry into physiological questions that may then be
followed by targeted laboratory studies.
PMID- 28424268
TI - Favorable outcome in patients with intracranial hemorrhage due to ruptured brain
AVM.
PMID- 28424269
TI - Risks and benefits of clopidogrel-aspirin in minor stroke or TIA: Time course
analysis of CHANCE.
AB - OBJECTIVE: To investigate the short-term time course risks and benefits of
clopidogrel with aspirin in minor ischemic stroke or TIA. METHODS: Data were
derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling
Cerebrovascular Events (CHANCE) trial. The primary outcome was a new ischemic
stroke. Safety outcomes included any bleeding and moderate to severe bleeding.
Time course analyses were performed for the outcomes of both stroke and bleeding.
RESULTS: A total of 145 (71.1%), 13 (6.4%), and 12 (5.9%) of 204 new ischemic
strokes in the clopidogrel-aspirin group vs 223 (75.6%), 19 (6.4%), and 8 (2.7%)
of 295 in the aspirin alone group occurred at the first, second, and third week,
respectively. A total of 23 (38.3%), 15 (25.0%), and 9 (15.0%) of 60 bleeding
cases in the clopidogrel-aspirin group vs 15 (36.6%), 8 (19.5%), and 3 (7.3%) of
41 in the aspirin alone group occurred at the first, second, and third week,
respectively. Clopidogrel-aspirin treatment numerically reduced the risk of
ischemic stroke within the first 2 weeks. From the 10th day, the number of any
bleeding cases caused by dual antiplatelets outweighed that of new stroke reduced
by dual antiplatelets. CONCLUSIONS: Clopidogrel-aspirin treatment may have a
benefit of reducing stroke risk outweighing the potential risk of increased
bleeding especially within the first 2 weeks compared with aspirin alone in
patients with minor stroke or TIA. CLINICALTRIALSGOV IDENTIFIER: NCT00979589.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for
patients with minor stroke or TIA, the reduction of stroke risk from clopidogrel
plus aspirin within the first 2 weeks outweighs the risk of bleeding compared
with aspirin alone.
PMID- 28424271
TI - Nrf2, cellular redox regulation, and neurologic implications.
PMID- 28424270
TI - Significance of circadian rhythms in severely brain-injured patients: A clue to
consciousness?
AB - OBJECTIVE: To investigate the relationship between the presence of a circadian
body temperature rhythm and behaviorally assessed consciousness levels in
patients with disorders of consciousness (DOC; i.e., vegetative
state/unresponsive wakefulness syndrome or minimally conscious state). METHODS:
In a cross-sectional study, we investigated the presence of circadian temperature
rhythms across 6 to 7 days using external skin temperature sensors in 18 patients
with DOC. Beyond this, we examined the relationship between behaviorally assessed
consciousness levels and circadian rhythmicity. RESULTS: Analyses with Lomb
Scargle periodograms revealed significant circadian rhythmicity in all patients
(range 23.5-26.3 hours). We found that especially scores on the arousal subscale
of the Coma Recovery Scale-Revised were closely linked to the integrity of
circadian variations in body temperature. Finally, we piloted whether bright
light stimulation could boost circadian rhythmicity and found positive evidence
in 2 out of 8 patients. CONCLUSION: The study provides evidence for an
association between circadian body temperature rhythms and arousal as a necessary
precondition for consciousness. Our findings also make a case for circadian
rhythms as a target for treatment as well as the application of diagnostic and
therapeutic means at times when cognitive performance is expected to peak.
PMID- 28424272
TI - Trends in dementia prevalence, incidence, and survival rate in a Japanese
community.
AB - OBJECTIVE: To investigate secular trends in the prevalence, incidence, and
survival rate of dementia in a Japanese elderly population in a comprehensive
manner. METHODS: Five cross-sectional surveys of dementia were conducted among
residents of a Japanese community, aged >=65 years, in 1985, 1992, 1998, 2005,
and 2012. We also established 2 cohorts consisting of the residents of this age
group without dementia in 1988 (n = 803) and 2002 (n = 1,231), and each was
followed for 10 years. RESULTS: The age-standardized prevalence of all-cause
dementia and Alzheimer disease (AD) increased with time (for all-cause dementia:
6.8% in 1985, 4.6% in 1992, 5.3% in 1998, 8.4% in 2005, and 11.3% in 2012, p for
trend <0.01; for AD: 1.5%, 1.4%, 2.4%, 3.9%, and 7.2%, respectively, p for trend
<0.01), while no secular change was observed for vascular dementia (VaD) (2.4%,
1.6%, 1.5%, 2.4%, and 2.4%, respectively, p for trend = 0.59). The age- and sex
adjusted incidence of all-cause dementia and AD, but not VaD, increased from the
1988 cohort to the 2002 cohort (for all-cause dementia: adjusted hazard ratio
[aHR] 1.68, 95% confidence interval [CI] 1.38-2.06; for AD: aHR 2.07, 95% CI 1.59
2.70; for VaD: aHR 1.18, 95% CI 0.83-1.69). The 5-year survival rate of all-cause
dementia and AD improved from the 1988 cohort to the 2002 cohort (for all-cause
dementia: 47.3% to 65.2%; for AD: 50.7% to 75.1%; all p < 0.01). CONCLUSIONS: The
increased incidence and improved survival rate of AD could have resulted in the
steep increase in AD prevalence in the Japanese elderly.
PMID- 28424273
TI - Certainty of genuine treatment increases drug responses among intellectually
disabled patients.
AB - OBJECTIVE: To determine the placebo component of treatment responses in patients
with intellectual disability (ID). METHODS: A statistical meta-analysis comparing
bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo
controlled clinical trials was performed, as these trial types represent
different certainty of receiving genuine treatment (100% vs 50%). Studies in
fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015
were considered. RESULTS: Seventeen open-label trials (n = 261, 65% male; mean
age 23.6 years; mean trial duration 38 weeks) and 22 placebo-controlled trials (n
= 721, 62% male; mean age 17.1 years; mean trial duration 35 weeks) were
included. The overall effect size from pre to post treatment in open-label
studies was g = 0.602 (p = 0.001). The effect of trial type was statistically
significant (p = 0.001), and revealed higher effect sizes in studies with 100%
likelihood of getting active drug, compared to both the drug and placebo arm of
placebo-controlled trials. We thus provide evidence for genuine placebo effects,
not explainable by natural history or regression toward the mean, among patients
with ID. CONCLUSIONS: Our data suggest that clinical trials in patients with
severe cognitive deficits are influenced by the certainty of receiving genuine
medication, and open-label design should thus not be used to evaluate the effect
of pharmacologic treatments in ID, as the results will be biased by an enhanced
placebo component.
PMID- 28424274
TI - Copeptin and NT-proBNP for prediction of all-cause and cardiovascular death in
ischemic stroke.
AB - OBJECTIVE: To evaluate long-term mortality in patients with acute ischemic stroke
(AIS) by exploring the correlation between death and plasma concentrations of
copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort
study. METHODS: In a prospective, multicenter observational study of 4,215
patients with AIS, copeptin and NT-proBNP levels were measured with a
standardized method when patients were admitted to hospital. The primary endpoint
was all-cause mortality or cardiovascular disease (CVD) mortality within 1 year.
RESULTS: During a follow-up period, 906 patients (20.1%, 95% confidence interval
[CI] 18.9-21.2) died, including 589 cases of CVD mortality (13.1%, 95% CI 12.1
14.0). With the use of a multivariate analysis, both markers were found to have
prognostic value in the same model (CVD mortality: odds ratio [OR] for fourth
quartile of copeptin and NT-proBNP 1.68 and 2.58, 95% CI 1.22-2.49 and 1.76-4.05,
respectively; all-cause mortality: OR for fourth quartile of copeptin and NT
proBNP 1.48 and 2.47, 95% CI 1.22-2.03 and 1.68-3.95, respectively). In a
receiver operating characteristics analysis of CVD mortality, the area under the
curve varied from 0.80 to 0.83 (95% CI 0.79-0.87) when the index of NT-proBNP was
added and increased to 0.86 (95% CI 0.83-0.90) when both markers were added.
CONCLUSIONS: Copeptin and NT-proBNP may be useful independent prognostic markers
of all-cause or CVD mortality in Chinese patients with AIS.
PMID- 28424275
TI - Outcomes after intracerebral hemorrhage from arteriovenous malformations.
AB - OBJECTIVE: To compare outcomes after intracerebral hemorrhage (ICH) from cerebral
arteriovenous malformation (AVM) rupture and other causes of ICH. METHODS: We
performed a retrospective population-based study using data from the Nationwide
Inpatient Sample. We used standard diagnosis codes to identify ICH cases from
2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were
inpatient mortality and home discharge. We used logistic regression to compare
outcomes between patients with ICH with and without AVM while adjusting for
demographics, comorbidities, and hospital characteristics. In a confirmatory
analysis using a prospective cohort of patients hospitalized with ICH at our
institution, we additionally adjusted for hematoma characteristics and the
Glasgow Coma Scale score. RESULTS: Among 619,167 ICH hospitalizations, the 4,485
patients (0.7%, 95% confidence interval [CI] 0.6-0.8) with an AVM were younger
and had fewer medical comorbidities than patients without AVM. After adjustment
for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5,
95% CI 0.4-0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4-3.0) than
patients without AVM. In a confirmatory analysis of 342 patients with ICH at our
institution, the 34 patients (9.9%, 95% CI 7.2-13.6) with a ruptured AVM had
higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4-13.1)
compared to patients without AVM. CONCLUSIONS: Patients with ICH due to ruptured
AVM have more favorable outcomes than patients with ICH from other causes.
PMID- 28424276
TI - Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor Dependent.
AB - Nephrotic syndrome is characterized by massive proteinuria and injury of
specialized glomerular epithelial cells called podocytes. Studies have shown
that, whereas low-concentration thrombin may be cytoprotective, higher thrombin
concentrations may contribute to podocyte injury. We and others have demonstrated
that ex vivo plasma thrombin generation is enhanced during nephrosis, suggesting
that thrombin may contribute to nephrotic progression. Moreover, nonspecific
thrombin inhibition has been shown to decrease proteinuria in nephrotic animal
models. We thus hypothesized that thrombin contributes to podocyte injury in a
protease-activated receptor-specific manner during nephrosis. Here, we show that
specific inhibition of thrombin with hirudin reduced proteinuria in two rat
nephrosis models, and thrombin colocalized with a podocyte-specific marker in rat
glomeruli. Furthermore, flow cytometry immunophenotyping revealed that rat
podocytes express the protease-activated receptor family of coagulation receptors
in vivo High-concentration thrombin directly injured conditionally immortalized
human and rat podocytes. Using receptor-blocking antibodies and activation
peptides, we determined that thrombin-mediated injury depended upon interactions
between protease-activated receptor 3 and protease-activated receptor 4 in human
podocytes, and between protease-activated receptor 1 and protease-activated
receptor 4 in rat podocytes. Proximity ligation and coimmunoprecipitation assays
confirmed thrombin-dependent interactions between human protease-activated
receptor 3 and protease-activated receptor 4, and between rat protease-activated
receptor 1 and protease-activated receptor 4 in cultured podocytes. Collectively,
these data implicate thrombinuria as a contributor to podocyte injury during
nephrosis, and suggest that thrombin and/or podocyte-expressed thrombin receptors
may be novel therapeutic targets for nephrotic syndrome.
PMID- 28424278
TI - Detection of HPV subtypes by mass spectrometry in FFPE tissue specimens: a
reliable tool for routine diagnostics.
AB - AIMS: Human papilloma virus (HPV) infection is a causative agent for
approximately 5% of all new cancer cases in humans. The virus is detected in
cervical, anal, vaginal, penile, vulvar and head and neck cancers and has
prognostic implications. Thus, test systems are required to detect high-risk but
also low-risk HPV subtypes with high specificity and sensitivity in a time
effective and cost-effective manner. In the present study we developed a new mass
spectrometry (MS)-based test system for the detection of HPV infections in
formalin-fixed paraffin-embedded (FFPE) tissue samples. METHODS: A high
throughput matrix-assisted laser desorption ionisation time of flight MS-based
assay was applied to genotype 19 HPV types in FFPE tissue specimens (n=46). The
results from the MS assay were compared with the results obtained from two
hybridisation-based test systems: the HPV 3.5 LCD-array kit and the EuroArrayHPV
system. RESULTS: In 36 out of 46 (78%) tissue samples, a HPV infection could be
detected by the MS-based HPV assay. In 16 samples (44%) only one and in 20
samples (56%) two to six HPV subtypes were identified. The overall agreement of
all three assays was almost perfect (Cohen's k value: 0.83). CONCLUSIONS: The MS
based assay is highly sensitive, reliable as well as cost-effective and
represents a suitable technology for the detection of HPV infections in FFPE
tissue material.
PMID- 28424277
TI - Janus Kinase 2 Regulates Transcription Factor EB Expression and Autophagy
Completion in Glomerular Podocytes.
AB - The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a
promising therapeutic target for the treatment of CKD. However, being
ubiquitously expressed in the adult, JAK2 is also likely to be necessary for
normal organ function. Here, we investigated the phenotypic effects of JAK2
deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an
elevation in urine albumin excretion that was accompanied by increased podocyte
autophagosome fractional volume and p62 aggregation, which are indicative of
impaired autophagy completion. In cultured podocytes, knockdown of JAK2 similarly
impaired autophagy and led to downregulation in the expression of lysosomal genes
and decreased activity of the lysosomal enzyme, cathepsin D. Because
transcription factor EB (TFEB) has recently emerged as a master regulator of
autophagosome-lysosome function, controlling the expression of several of the
genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated by
JAK2. In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter
activity, expression, and nuclear localization. In silico analysis and chromatin
immunoprecipitation assays revealed that the downstream mediator of JAK2
signaling STAT1 binds to the TFEB promoter. Finally, overexpression of TFEB in
JAK2-deficient podocytes reversed lysosomal dysfunction and restored albumin
permselectivity. Collectively, these observations highlight the homeostatic
actions of JAK2 in podocytes and the importance of TFEB to autophagosome-lysosome
function in these cells. These results also raise the possibility that
therapeutically modulating TFEB activity may improve podocyte health in
glomerular disease.
PMID- 28424279
TI - Phosphorylation Induces Structural Changes in the Autographa californica
Nucleopolyhedrovirus P10 Protein.
AB - Baculoviruses encode a variety of auxiliary proteins that are not essential for
viral replication but provide them with a selective advantage in nature. P10 is a
10-kDa auxiliary protein produced in the very late phase of gene transcription by
Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The P10 protein
forms cytoskeleton-like structures in the host cell that associate with
microtubules varying from filamentous forms in the cytoplasm to aggregated
perinuclear tubules that form a cage-like structure around the nucleus. These P10
structures may have a role in the release of occlusion bodies (OBs) and thus
mediate the horizontal transmission of the virus between insect hosts. Here,
using mass spectrometric analysis, it is demonstrated that the C terminus of P10
is phosphorylated during virus infection of cells in culture. Analysis of P10
mutants encoded by recombinant baculoviruses in which putative phosphorylation
residues were mutated to alanine showed that serine 93 is a site of
phosphorylation. Confocal microscopy examination of the serine 93 mutant
structures revealed aberrant formation of the perinuclear tubules. Thus, the
phosphorylation of serine 93 may induce the aggregation of filaments to form
tubules. Together, these data suggest that the phosphorylation of serine 93
affects the structural conformation of P10.IMPORTANCE The baculovirus P10 protein
has been researched intensively since it was first observed in 1969, but its role
during viral infection remains unclear. It is conserved in the alphabaculoviruses
and expressed at high levels during virus infection. Producing large amounts of a
protein is wasteful for the virus unless it is advantageous for the survival of
its progeny, and therefore, P10 presents an enigma. As P10 polymerizes to form
organized cytoskeletal structures that colocalize with host cell microtubules,
the structural relationship of the protein with the host cell may present a key
to help understand the function and importance of this protein. This study
addresses the importance of the structural changes in P10 during infection and
how they may be governed by phosphorylation. The P10 structures affected by
phosphorylation are closely associated with the viral progeny and thus may
potentially be responsible for its dissemination and survival.
PMID- 28424280
TI - The Major Envelope Glycoprotein of Murid Herpesvirus 4 Promotes Sexual
Transmission.
AB - Gammaherpesviruses are important human and animal pathogens. Infection control
has proven difficult because the key process of transmission is ill understood.
Murid herpesvirus 4 (MuHV-4), a gammaherpesvirus of mice, is transmitted
sexually. We show that this depends on the major virion envelope glycoprotein
gp150. gp150 is redundant for host entry, and in vitro, it regulates rather than
promotes cell binding. We show that gp150-deficient MuHV-4 reaches and replicates
normally in the female genital tract after nasal infection but is poorly released
from vaginal epithelial cells and fails to pass from the female to the male
genital tract during sexual contact. Thus, we show that the regulation of virion
binding is a key component of spontaneous gammaherpesvirus
transmission.IMPORTANCE Gammaherpesviruses are responsible for many important
diseases in both animals and humans. Some important aspects of their life cycle
are still poorly understood. Key among these is viral transmission. Here we show
that the major envelope glycoprotein of murid herpesvirus 4 functions not in
entry or dissemination but in virion release to allow sexual transmission to new
hosts.
PMID- 28424281
TI - Distinct Roles of Vaccinia Virus NF-kappaB Inhibitor Proteins A52, B15, and K7 in
the Immune Response.
AB - Poxviruses use a complex strategy to escape immune control, by expressing
immunomodulatory proteins that could limit their use as vaccine vectors. To test
the role of poxvirus NF-kappaB pathway inhibitors A52, B15, and K7 in immunity,
we deleted their genes in an NYVAC (New York vaccinia virus) strain that
expresses HIV-1 clade C antigens. After infection of mice, ablation of the A52R,
B15R, and K7R genes increased dendritic cell, natural killer cell, and neutrophil
migration as well as chemokine/cytokine expression. Revertant viruses with these
genes confirmed their role in inhibiting the innate immune system. To different
extents, enhanced innate immune responses correlated with increased HIV Pol- and
Gag-specific polyfunctional CD8 T cell and HIV Env-specific IgG responses induced
by single-, double-, and triple-deletion mutants. These poxvirus proteins thus
influence innate and adaptive cell-mediated and humoral immunity, and their
ablation offers alternatives for design of vaccine vectors that regulate immune
responses distinctly.IMPORTANCE Poxvirus vectors are used in clinical trials as
candidate vaccines for several pathogens, yet how these vectors influence the
immune system is unknown. We developed distinct poxvirus vectors that express
heterologous antigens but lack different inhibitors of the central host-cell
signaling pathway. Using mice, we studied the capacity of these viruses to induce
innate and adaptive immune responses and showed that these vectors can distinctly
regulate the magnitude and quality of these responses. These findings provide
important insights into the mechanism of poxvirus-induced immune response and
alternative strategies for vaccine vector design.
PMID- 28424282
TI - Formation of a Viral Replication Focus in Sulfolobus Cells Infected by the
Rudivirus Sulfolobus islandicus Rod-Shaped Virus 2.
AB - Viral factories are compartmentalized centers for viral replication and assembly
in infected eukaryotic cells. Here, we report the formation of a replication
focus by prototypical archaeal Sulfolobus islandicus rod-shaped virus 2 (SIRV2)
in the model archaeon Sulfolobus This rod-shaped virus belongs to the viral
family Rudiviridae, carrying linear double-stranded DNA (dsDNA) genomes, which
are very common in geothermal environments. We demonstrate that SIRV2 DNA
synthesis is confined to a focus near the periphery of infected cells. Moreover,
viral and cellular replication proteins are recruited to, and concentrated in,
the viral replication focus. Furthermore, we show that of the four host DNA
polymerases (DNA polymerase I [Dpo1] to Dpo4), only Dpo1 participates in viral
DNA synthesis. This constitutes the first report of the formation of a viral
replication focus in archaeal cells, suggesting that organization of viral
replication in foci is a widespread strategy employed by viruses of the three
domains of life.IMPORTANCE The organization of viral replication in foci or viral
factories has been mostly described for different eukaryotic viruses and for
several bacteriophages. This work constitutes the first report of the formation
of a viral replication center by a virus infecting members of the Archaea domain.
PMID- 28424283
TI - Simian Immunodeficiency Virus Targeting of CXCR3+ CD4+ T Cells in Secondary
Lymphoid Organs Is Associated with Robust CXCL10 Expression in
Monocyte/Macrophage Subsets.
AB - Glycosylation of Env defines pathogenic properties of simian immunodeficiency
virus (SIV). We previously demonstrated that pathogenic SIVmac239 and a live
attenuated, quintuple deglycosylated Env mutant (Delta5G) virus target CD4+ T
cells residing in different tissues during acute infection. SIVmac239 and Delta5G
preferentially infected distinct CD4+ T cells in secondary lymphoid organs (SLOs)
and within the lamina propria of the small intestine, respectively (C. Sugimoto
et al., J Virol 86:9323-9336, 2012, https://doi.org/10.1128/JVI.00948-12). Here,
we studied the host responses relevant to SIV targeting of CXCR3+ CCR5+ CD4+ T
cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized
inflammatory responses, defined by expression of CXCR3 chemokines, were
distinctly induced in the SIVmac239-infected animals. Consistent with robust
expression of CXCL10, CXCR3+ T cells were depleted from blood in the SIVmac239
infected animals. We also discovered that elevation of CXCL10 expression in blood
and SLOs was secondary to the induction of CD14+ CD16+ monocytes and MAC387+
macrophages, respectively. Since the significantly higher levels of SIV infection
in SLOs occurred with a massive accumulation of infiltrated MAC387+ macrophages,
T cells, dendritic cells (DCs), and residential macrophages near high endothelial
venules, the results highlight critical roles of innate/inflammatory responses in
SIVmac239 infection. Restricted infection in SLOs by Delta5G also suggests that
glycosylation of Env modulates innate/inflammatory responses elicited by cells of
monocyte/macrophage/DC lineages.IMPORTANCE We previously demonstrated that a
pathogenic SIVmac239 virus and a live-attenuated, deglycosylated mutant Delta5G
virus infected distinct CD4+ T cell subsets in SLOs and the small intestine,
respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012,
https://doi.org/10.1128/JVI.00948-12). Accordingly, infections with SIVmac239,
but not with Delta5G, deplete CXCR3+ CCR5+ CD4+ T (Th1) cells during the primary
infection, thereby compromising the cellular immune response. Thus, we
hypothesized that distinct host responses are elicited by the infections with two
different viruses. We found that SIVmac239 induced distinctly higher levels of
inflammatory Th1 responses than Delta5G. In particular, SIVmac239 infection
elicited robust expression of CXCL10, a chemokine for CXCR3+ cells, in CD14+
CD16+ monocytes and MAC387+ macrophages recently infiltrated in SLOs. In
contrast, Delta5G infection elicited only modest inflammatory responses. These
results suggest that the glycosylation of Env modulates the inflammatory/Th1
responses through the monocyte/macrophage subsets and elicits marked differences
in SIV infection and clinical outcomes.
PMID- 28424284
TI - A Novel Type of Polyhedral Viruses Infecting Hyperthermophilic Archaea.
AB - Encapsidation of genetic material into polyhedral particles is one of the most
common structural solutions employed by viruses infecting hosts in all three
domains of life. Here, we describe a new virus of hyperthermophilic archaea,
Sulfolobus polyhedral virus 1 (SPV1), which condenses its circular double
stranded DNA genome in a manner not previously observed for other known viruses.
The genome complexed with virion proteins is wound up sinusoidally into a
spherical coil which is surrounded by an envelope and further encased by an outer
polyhedral capsid apparently composed of the 20-kDa virion protein. Lipids
selectively acquired from the pool of host lipids are integral constituents of
the virion. None of the major virion proteins of SPV1 show similarity to
structural proteins of known viruses. However, minor structural proteins, which
are predicted to mediate host recognition, are shared with other
hyperthermophilic archaeal viruses infecting members of the order Sulfolobales
The SPV1 genome consists of 20,222 bp and contains 45 open reading frames, only
one-fifth of which could be functionally annotated.IMPORTANCE Viruses infecting
hyperthermophilic archaea display a remarkable morphological diversity, often
presenting architectural solutions not employed by known viruses of bacteria and
eukaryotes. Here we present the isolation and characterization of Sulfolobus
polyhedral virus 1, which condenses its genome into a unique spherical coil. Due
to the original genomic and architectural features of SPV1, the virus should be
considered a representative of a new viral family, "Portogloboviridae."
PMID- 28424285
TI - Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8+ T and
CD21+ B Lymphocytes but Not for Glandular Epithelium at the Primary Site of
Persistent Infection in the Stallion Reproductive Tract.
AB - Equine arteritis virus (EAV) has a global impact on the equine industry as the
causative agent of equine viral arteritis (EVA), a respiratory, systemic, and
reproductive disease of equids. A distinctive feature of EAV infection is that it
establishes long-term persistent infection in 10 to 70% of infected stallions
(carriers). In these stallions, EAV is detectable only in the reproductive tract,
and viral persistence occurs despite the presence of high serum neutralizing
antibody titers. Carrier stallions constitute the natural reservoir of the virus
as they continuously shed EAV in their semen. Although the accessory sex glands
have been implicated as the primary sites of EAV persistence, the viral host cell
tropism and whether viral replication in carrier stallions occurs in the presence
or absence of host inflammatory responses remain unknown. In this study, dual
immunohistochemical and immunofluorescence techniques were employed to
unequivocally demonstrate that the ampulla is the main EAV tissue reservoir
rather than immunologically privileged tissues (i.e., testes). Furthermore, we
demonstrate that EAV has specific tropism for stromal cells (fibrocytes and
possibly tissue macrophages) and CD8+ T and CD21+ B lymphocytes but not glandular
epithelium. Persistent EAV infection is associated with moderate, multifocal
lymphoplasmacytic ampullitis comprising clusters of B (CD21+) lymphocytes and
significant infiltration of T (CD3+, CD4+, CD8+, and CD25+) lymphocytes, tissue
macrophages, and dendritic cells (Iba-1+ and CD83+), with a small number of
tissue macrophages expressing CD163 and CD204 scavenger receptors. This study
suggests that EAV employs complex immune evasion mechanisms that warrant further
investigation.IMPORTANCE The major challenge for the worldwide control of EAV is
that this virus has the distinctive ability to establish persistent infection in
the stallion's reproductive tract as a mechanism to ensure its maintenance in
equid populations. Therefore, the precise identification of tissue and cellular
tropism of EAV is critical for understanding the molecular basis of viral
persistence and for development of improved prophylactic or treatment strategies.
This study significantly enhances our understanding of the EAV carrier state in
stallions by unequivocally identifying the ampullae as the primary sites of viral
persistence, combined with the fact that persistence involves continuous viral
replication in fibrocytes (possibly including tissue macrophages) and T and B
lymphocytes in the presence of detectable inflammatory responses, suggesting the
involvement of complex viral mechanisms of immune evasion. Therefore, EAV
persistence provides a powerful new natural animal model to study RNA virus
persistence in the male reproductive tract.
PMID- 28424286
TI - Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are
Consistent with Intersubtype Differences in HIV-1 Disease Progression.
AB - There are marked differences in the spread and prevalence of HIV-1 subtypes
worldwide, and differences in clinical progression have been reported. However,
the biological reasons underlying these differences are unknown. Gag-protease is
essential for HIV-1 replication, and Gag-protease-driven replication capacity has
previously been correlated with disease progression. We show that Gag-protease
replication capacity correlates significantly with that of whole isolates (r =
0.51; P = 0.04), indicating that Gag-protease is a significant contributor to
viral replication capacity. Furthermore, we investigated subtype-specific
differences in Gag-protease-driven replication capacity using large well
characterized cohorts in Africa and the Americas. Patient-derived Gag-protease
sequences were inserted into an HIV-1 NL4-3 backbone, and the replication
capacities of the resulting recombinant viruses were measured in an HIV-1
inducible reporter T cell line by flow cytometry. Recombinant viruses expressing
subtype C Gag-proteases exhibited substantially lower replication capacities than
those expressing subtype B Gag-proteases (P < 0.0001); this observation remained
consistent when representative Gag-protease sequences were engineered into an HIV
1 subtype C backbone. We identified Gag residues 483 and 484, located within the
Alix-binding motif involved in virus budding, as major contributors to subtype
specific replicative differences. In East African cohorts, we observed a
hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C < D <
intersubtype recombinants (P < 0.0029), which is consistent with reported
intersubtype differences in disease progression. We thus hypothesize that the
lower Gag-protease-driven replication capacity of subtypes A and C slows disease
progression in individuals infected with these subtypes, which in turn leads to
greater opportunity for transmission and thus increased prevalence of these
subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there
are reported differences in their rates of disease progression and epidemic
spread. The biological determinants underlying these differences have not been
fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication
capacity correlates with the replication capacity of whole virus isolates. We
further show that subtype B displays a significantly higher Gag-protease-mediated
replication capacity than does subtype C, and we identify a major genetic
determinant of these differences. Moreover, in two independent East African
cohorts we demonstrate a reproducible hierarchy of Gag-protease-driven
replicative capacity, whereby recombinants exhibit the greatest replication,
followed by subtype D, followed by subtypes A and C. Our data identify Gag
protease as a major determinant of subtype differences in disease progression
among HIV-1 subtypes; furthermore, we propose that the poorer viral replicative
capacity of subtypes A and C may paradoxically contribute to their more efficient
spread in sub-Saharan Africa.
PMID- 28424287
TI - Protective Efficacies of Formaldehyde-Inactivated Whole-Virus Vaccine and
Antivirals in a Murine Model of Coxsackievirus A10 Infection.
AB - Coxsackievirus A10 (CVA10) is one of the major pathogens associated with hand,
foot, and mouth disease (HFMD). CVA10 infection can cause herpangina and viral
pneumonia, which can be complicated by severe neurological sequelae. The
morbidity and mortality of CVA10-associated HFMD have been increasing in recent
years, particularly in the pan-Pacific region. There are limited studies,
however, on the pathogenesis and immunology of CVA10-associated HFMD infections,
and few antiviral drugs or vaccines have been reported. In the present study, a
cell-adapted CVA10 strain was employed to inoculate intramuscularly 5-day-old ICR
mice, which developed significant clinical signs, including reduced mobility,
lower weight gain, and quadriplegia, with significant pathology in the brain,
hind limb skeletal muscles, and lungs of infected mice in the moribund state. The
severity of illness was associated with abnormally high expression of the
proinflammatory cytokine interleukin 6 (IL-6). Antiviral assays demonstrated that
ribavirin and gamma interferon administration could significantly inhibit CVA10
replication both in vitro and in vivo In addition, formaldehyde-inactivated CVA10
whole-virus vaccines induced immune responses in adult mice, and maternal
neutralizing antibodies could be transmitted to neonatal mice, providing
protection against CVA10 clinical strains. Furthermore, high-titer antisera were
effective against CVA10 and could relieve early clinical symptoms and improve the
survival rates of CVA10-challenged neonatal mice. In summary, we present a novel
murine model to study CVA10 pathology that will be extremely useful in developing
effective antivirals and vaccines to diminish the burden of HFMD-associated
disease.IMPORTANCE Hand, foot, and mouth disease cases in infancy, arising from
coxsackievirus A10 (CVA10) infections, are typically benign, resolving without
any significant adverse events. Severe disease and fatalities, however, can occur
in some children, necessitating the development of vaccines and antiviral
therapies. The present study has established a newborn-mouse model of CVA10 that,
importantly, recapitulates many aspects of human disease with respect to the
neuropathology and skeletal muscle pathology. We found that high levels of the
proinflammatory cytokine interleukin 6 correlated with disease severity and that
ribavirin and gamma interferon could decrease viral titers in vitro and in vivo
Whole-virus vaccines produced immune responses in adult mice, and immunized
mothers conferred protection on neonates against challenge from CVA10 clinical
strains. Passive immunization with high-titer antisera could also improve
survival rates in newborn animals.
PMID- 28424288
TI - Virion-Associated Vpr Alleviates a Postintegration Block to HIV-1 Infection of
Dendritic Cells.
AB - Viral protein R (Vpr) is an HIV-1 accessory protein whose function remains poorly
understood. In this report, we sought to determine the requirement of Vpr for
facilitating HIV-1 infection of monocyte-derived dendritic cells (MDDCs), one of
the first cell types to encounter virus in the peripheral mucosal tissues. In
this report, we characterize a significant restriction of Vpr-deficient virus
replication and spread in MDDCs alone and in cell-to-cell spread in MDDC-CD4+ T
cell cocultures. This restriction of HIV-1 replication in MDDCs was observed in a
single round of virus replication and was rescued by the expression of Vpr in
trans in the incoming virion. Interestingly, infections of MDDCs with viruses
that encode Vpr mutants unable to interact with either the DCAF1/DDB1 E3
ubiquitin ligase complex or a host factor hypothesized to be targeted for
degradation by Vpr also displayed a significant replication defect. While the
extent of proviral integration in HIV-1-infected MDDCs was unaffected by the
absence of Vpr, the transcriptional activity of the viral long terminal repeat
(LTR) from Vpr-deficient proviruses was significantly reduced. Together, these
results characterize a novel postintegration restriction of HIV-1 replication in
MDDCs and show that the interaction of Vpr with the DCAF1/DDB1 E3 ubiquitin
ligase complex and the yet-to-be-identified host factor might alleviate this
restriction by inducing transcription from the viral LTR. Taken together, these
findings identify a robust in vitro cell culture system that is amenable to
addressing mechanisms underlying Vpr-mediated enhancement of HIV-1
replication.IMPORTANCE Despite decades of work, the function of the HIV-1 protein
Vpr remains poorly understood, primarily due to the lack of an in vitro cell
culture system that demonstrates a deficit in replication upon infection with
viruses in the absence of Vpr. In this report, we describe a novel cell infection
system that utilizes primary human dendritic cells, which display a robust
decrease in viral replication upon infection with Vpr-deficient HIV-1. We show
that this replication difference occurs in a single round of infection and is due
to decreased transcriptional output from the integrated viral genome. Viral
transcription could be rescued by virion-associated Vpr. Using mutational
analysis, we show that domains of Vpr involved in binding to the DCAF1/DDB1/E3
ubiquitin ligase complex and prevention of cell cycle progression into mitosis
are required for LTR-mediated viral expression, suggesting that the
evolutionarily conserved G2 cell cycle arrest function of Vpr is essential for
HIV-1 replication.
PMID- 28424290
TI - Skin-derived precursors from human subjects with Type 2 diabetes yield
dysfunctional vascular smooth muscle cells.
AB - : Objective: Few methods enable molecular and cellular studies of vascular aging
or Type 2 diabetes (T2D). Here, we report a new approach to studying human
vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs
differentiated from progenitors found in skin. Approach and results: Skin-derived
precursors (SKPs) were cultured from biopsies (N=164, ~1 cm2) taken from the
edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7 +/-
13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at
high efficiency (>80% yield). The number of SKPs isolated from subjects with T2D
was ~50% lower than those without T2D (cells/g: 0.18 +/- 0.03, N=58 versus 0.40
+/- 0.05, N=100, P<0.05). Importantly, SKP-derived VSMCs from subjects with T2D
had higher Fluo-5F-determined baseline cytosolic Ca2+ concentrations (AU: 1,968
+/- 160, N=7 versus 1,386 +/- 170, N=13, P<0.05), and a trend toward greater Ca2+
cycling responses to norepinephrine (NE) (AUC: 177,207 +/- 24,669, N=7 versus
101,537 +/- 15,881, N=20, P<0.08) despite a reduced frequency of Ca2+ cycling
(events s-1 cell-1: 0.011 +/- 0.004, N=8 versus 0.021 +/- 0.003, N=19, P<0.05)
than those without T2D. SKP-derived VSMCs from subjects with T2D also manifest
enhanced sensitivity to phenylephrine (PE) in an impedance-based assay (EC50 nM:
72.3 +/- 63.6, N=5 versus 3,684 +/- 3,122, N=9, P<0.05), and impaired wound
closure in vitro (% closure: 21.9 +/- 3.6, N=4 versus 67.0 +/- 10.3, N=4,
P<0.05). Compared with aortic- and saphenous vein-derived primary VSMCs, SKP
derived VSMCs are functionally distinct, but mirror defects of T2D also exhibited
by primary VSMCs. CONCLUSION: Skin biopsies from older adults yield sufficient
SKPs to differentiate VSMCs, which reveal abnormal phenotypes of T2D that survive
differentiation and persist even after long-term normoglycemic culture.
PMID- 28424289
TI - Disruption of MDA5-Mediated Innate Immune Responses by the 3C Proteins of
Coxsackievirus A16, Coxsackievirus A6, and Enterovirus D68.
AB - Coxsackievirus A16 (CV-A16), CV-A6, and enterovirus D68 (EV-D68) belong to the
Picornaviridae family and are major causes of hand, foot, and mouth disease
(HFMD) and pediatric respiratory disease worldwide. The biological
characteristics of these viruses, especially their interplay with the host innate
immune system, have not been well investigated. In this study, we discovered that
the 3Cpro proteins from CV-A16, CV-A6, and EV-D68 bind melanoma differentiation
associated gene 5 (MDA5) and inhibit its interaction with MAVS. Consequently,
MDA5-triggered type I interferon (IFN) signaling in the retinoic acid-inducible
gene I-like receptor (RLR) pathway was blocked by the CV-A16, CV-A6, and EV-D68
3Cpro proteins. Furthermore, the CV-A16, CV-A6, and EV-D68 3Cpro proteins all
cleave transforming growth factor beta-activated kinase 1 (TAK1), resulting in
the inhibition of NF-kappaB activation, a host response also critical for Toll
like receptor (TLR)-mediated signaling. Thus, our data demonstrate that
circulating HFMD-associated CV-A16 and CV-A6, as well as severe respiratory
disease-associated EV-D68, have developed novel mechanisms to subvert host innate
immune responses by targeting key factors in the RLR and TLR pathways. Blocking
the ability of 3Cpro proteins from diverse enteroviruses and coxsackieviruses to
interfere with type I IFN induction should restore IFN antiviral function,
offering a potential novel antiviral strategy.IMPORTANCE CV-A16, CV-A6, and EV
D68 are emerging pathogens associated with hand, foot, and mouth disease and
pediatric respiratory disease worldwide. The pathogenic mechanisms of these
viruses are largely unknown. Here we demonstrate that the CV-A16, CV-A6, and EV
D68 3Cpro proteins block MDA5-triggered type I IFN induction. The 3Cpro proteins
of these viruses bind MDA5 and inhibit its interaction with MAVS. In addition,
the CV-A16, CV-A6, and EV-D68 3Cpro proteins cleave TAK1 to inhibit the NF-kappaB
response. Thus, our data demonstrate that circulating HFMD-associated CV-A16 and
CV-A6, as well as severe respiratory disease-associated EV-D68, have developed a
mechanism to subvert host innate immune responses by simultaneously targeting key
factors in the RLR and TLR pathways. These findings indicate the potential merit
of targeting the CV-A16, CV-A6, and EV-D68 3Cpro proteins as an antiviral
strategy.
PMID- 28424291
TI - Comparison of optomotor and optokinetic reflexes in mice.
AB - During animal locomotion or position adjustments, the visual system uses image
stabilization reflexes to compensate for global shifts in the visual scene. These
reflexes elicit compensatory head movements (optomotor response, OMR) in
unrestrained animals or compensatory eye movements (optokinetic response, OKR) in
head-fixed or unrestrained animals exposed to globally rotating striped patterns.
In mice, OMR are relatively easy to observe and find broad use in the rapid
evaluation of visual function. OKR determinations are more involved
experimentally but yield more stereotypical, easily quantifiable results. The
relative contributions of head and eye movements to image stabilization in mice
have not been investigated. We are using newly developed software and apparatus
to accurately quantitate mouse head movements during OMR, quantitate eye
movements during OKR, and determine eye movements in freely behaving mice. We
provide the first direct comparison of OMR and OKR gains (head or eye
velocity/stimulus velocity) and find that the two reflexes have comparable
dependencies on stimulus luminance, contrast, spatial frequency, and velocity.
OMR and OKR are similarly affected in genetically modified mice with defects in
retinal ganglion cells (RGC) compared with wild-type, suggesting they are driven
by the same sensory input (RGC type). OKR eye movements have much higher gains
than the OMR head movements, but neither can fully compensate global visual
shifts. However, combined eye and head movements can be detected in unrestrained
mice performing OMR, suggesting they can cooperate to achieve image
stabilization, as previously described for other species.NEW & NOTEWORTHY We
provide the first quantitation of head gain during optomotor response in mice and
show that optomotor and optokinetic responses have similar psychometric curves.
Head gains are far smaller than eye gains. Unrestrained mice combine head and eye
movements to respond to visual stimuli, and both monocular and binocular fields
are used during optokinetic responses. Mouse OMR and OKR movements are
heterogeneous under optimal and suboptimal stimulation and are affected in mice
lacking ON direction-selective retinal ganglion cells.
PMID- 28424292
TI - Loss and recovery of functional connectivity in cultured cortical networks
exposed to hypoxia.
AB - In the core of a brain infarct, loss of neuronal function is followed by neuronal
death within minutes. In an area surrounding the core (penumbra), some perfusion
remains. Here, neurons initially remain structurally intact, but massive synaptic
failure strongly reduces neural activity. Activity in the penumbra may eventually
recover or further deteriorate toward massive cell death. Besides activity
recovery, return of brain functioning requires restoration of connectivity.
However, low activity has been shown to initiate compensatory mechanisms that
affect network connectivity. We investigated the effect of transient hypoxia and
compensatory mechanisms on activity and functional connectivity using cultured
cortical networks on multielectrode arrays. Networks were exposed to hypoxia of
controlled depth (10-90% of normoxia) and duration (6-48 h). First, we determined
how hypoxic depth and duration govern activity recovery. Then, we investigated
connectivity changes during and after hypoxic incidents, mild enough for activity
to recover. Shortly after hypoxia onset, activity and connectivity decreased.
Following 4-6 h of ongoing hypoxia, we observed partial recovery. Only if the
hypoxic burden was limited did connectivity show further recovery upon return to
normoxia. Partial recovery during hypoxia was dominated by restored baseline
connections, rather than newly formed ones. Baseline strengths of surviving
(persisting or recovered) and lost connections did not differ nor did baseline
activity at their "presynaptic" electrodes. However, "postsynaptic" electrodes of
surviving connections were significantly more active during baseline than those
of lost connections. This implies that recovery during hypoxia reflects an
effective mechanism to restore network activity, which does not necessarily
conserve prehypoxia connectivity.NEW & NOTEWORTHY Hypoxia reduced the firing
rates of cultured neurons. Depending on hypoxic depth and duration, activity
recovered during hypoxia and upon return to normoxia. Recovery (partial) during
hypoxia was associated with restored baseline connections rather than newly
formed ones. Predominantly, baseline connections with most active postsynaptic
electrodes recovered, supporting the notion of effective activity homeostasis.
This compensatory mechanism remained effective during ~20 h of hypoxia. Beyond 20
h of compensation, loss of activity and connectivity became irreversible.
PMID- 28424293
TI - Prediction suppression and surprise enhancement in monkey inferotemporal cortex.
AB - Exposing monkeys, over the course of days and weeks, to pairs of images presented
in fixed sequence, so that each leading image becomes a predictor for the
corresponding trailing image, affects neuronal visual responsiveness in area TE.
At the end of the training period, neurons respond relatively weakly to a
trailing image when it appears in a trained sequence and, thus, confirms
prediction, whereas they respond relatively strongly to the same image when it
appears in an untrained sequence and, thus, violates prediction. This effect
could arise from prediction suppression (reduced firing in response to the
occurrence of a probable event) or surprise enhancement (elevated firing in
response to the omission of a probable event). To identify its cause, we compared
firing under the prediction-confirming and prediction-violating conditions to
firing under a prediction-neutral condition. The results provide strong evidence
for prediction suppression and limited evidence for surprise enhancement.NEW &
NOTEWORTHY In predictive coding models of the visual system, neurons carry signed
prediction error signals. We show here that monkey inferotemporal neurons exhibit
prediction-modulated firing, as posited by these models, but that the signal is
unsigned. The response to a prediction-confirming image is suppressed, and the
response to a prediction-violating image may be enhanced. These results are
better explained by a model in which the visual system emphasizes unpredicted
events than by a predictive coding model.
PMID- 28424294
TI - GABA and primary motor cortex inhibition in young and older adults: a multimodal
reliability study.
AB - The effects of healthy aging on gamma-aminobutyric acid (GABA) within primary
motor cortex (M1) remain poorly understood. Studies have reported contrasting
results, potentially due to limitations with the common assessment technique. The
aim of the present study was to investigate the effect of healthy aging on M1
GABA concentration and neurotransmission using a multimodal approach. Fifteen
young and sixteen older adults participated in this study. Magnetic resonance
spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and
threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols
were used to examine cortical silent period duration, short- and long-interval
intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD).
The reliability of TMS measures was examined with intraclass correlation
coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 +/- 2.59%)
compared with young (25.66 +/- 1.44%; P = 0.002). However, there was no age
related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD
(all P > 0.66). The intersession reliability of threshold-tracking measures was
good to excellent for both young (range 0.75-0.96) and older adults (range 0.88
0.93). Our findings indicate that extrasynaptic inhibition may be reduced with
advancing age, whereas GABA concentration and synaptic inhibition are maintained.
Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment
of M1 GABA concentration and neurotransmission, respectively, in young and older
adults.NEW & NOTEWORTHY gamma-Aminobutyric acid (GABA) in primary motor cortex
was assessed in young and older adults using magnetic resonance spectroscopy and
threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults
exhibited reduced extrasynaptic inhibition (short-interval intracortical
inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic
inhibition were similar between age groups. We demonstrate that magnetic
resonance spectroscopy and threshold-tracking provide valid and reliable
assessments of primary motor cortex GABA concentration and neurotransmission,
respectively.
PMID- 28424295
TI - The sensorimotor system minimizes prediction error for object lifting when the
object's weight is uncertain.
AB - A reliable mechanism to predict the heaviness of an object is important for
manipulating an object under environmental uncertainty. Recently, Cashaback et
al. (Cashaback JGA, McGregor HR, Pun HCH, Buckingham G, Gribble PL. J
Neurophysiol 117: 260-274, 2017) showed that for object lifting the sensorimotor
system uses a strategy that minimizes prediction error when the object's weight
is uncertain. Previous research demonstrates that visually guided reaching is
similarly optimized. Although this suggests a unified strategy of the
sensorimotor system for object manipulation, the selected strategy appears to be
task dependent and subject to change in response to the degree of environmental
uncertainty.
PMID- 28424298
TI - Stress-Related Memory Impairments Are Modulated by the Synergistic Action of
Stress Hormones: Implications for PTSD.
PMID- 28424297
TI - Magnitude and behavior of cross-talk effects in multichannel electrophysiology
experiments.
AB - Modern neurophysiological experiments frequently involve multiple channels
separated by very small distances. A unique methodological concern for multiple
electrode experiments is that of capacitive coupling (cross-talk) between
channels. Yet the nature of the cross-talk recording circuit is not well known in
the field, and the extent to which it practically affects neurophysiology
experiments has never been fully investigated. Here we describe a simple
electrical circuit model of simultaneous recording and stimulation with two or
more channels and experimentally verify the model using ex vivo brain slice and
in vivo whole-brain preparations. In agreement with the model, we find that cross
talk amplitudes increase nearly linearly with the impedance of a recording
electrode and are larger for higher frequencies. We demonstrate cross-talk
contamination of action potential waveforms from intracellular to extracellular
channels, which is observable in part because of the different orders of
magnitude between the channels. This contamination is electrode impedance
dependent and matches predictions from the model. We use recently published
parameters to simulate cross-talk in high-density multichannel extracellular
recordings. Cross-talk effectively spatially smooths current source density (CSD)
estimates in these recordings and induces artefactual phase shifts where
underlying voltage gradients occur; however, these effects are modest. We show
that the effects of cross-talk are unlikely to affect most conclusions inferred
from neurophysiology experiments when both originating and receiving electrode
record signals of similar magnitudes. We discuss other types of experiments and
analyses that may be susceptible to cross-talk, techniques for detecting and
experimentally reducing cross-talk, and implications for high-density probe
design.NEW & NOTEWORTHY We develop and experimentally verify an electrical
circuit model describing cross-talk that necessarily occurs between two channels.
Recorded cross-talk increased with electrode impedance and signal frequency. We
recorded cross-talk contamination of spike waveforms from intracellular to
extracellular channels. We simulated high-density multichannel extracellular
recordings and demonstrate spatial smoothing and phase shifts that cross-talk
enacts on CSD measurements. However, when channels record similar-magnitude
signals, effects are modest and unlikely to affect most conclusions.
PMID- 28424299
TI - Adult Neural Stem Cell Multipotency and Differentiation Are Directed by the
Methyl-CpG-Binding Protein MBD1.
PMID- 28424296
TI - Cell type-specific changes in retinal ganglion cell function induced by rod death
and cone reorganization in rats.
AB - We have determined the impact of rod death and cone reorganization on the
spatiotemporal receptive fields (RFs) and spontaneous activity of distinct
retinal ganglion cell (RGC) types. We compared RGC function between healthy and
retinitis pigmentosa (RP) model rats (S334ter-3) at a time when nearly all rods
were lost but cones remained. This allowed us to determine the impact of rod
death on cone-mediated visual signaling, a relevant time point because the
diagnosis of RP frequently occurs when patients are nightblind but daytime vision
persists. Following rod death, functionally distinct RGC types persisted; this
indicates that parallel processing of visual input remained largely intact.
However, some properties of cone-mediated responses were altered ubiquitously
across RGC types, such as prolonged temporal integration and reduced spatial RF
area. Other properties changed in a cell type-specific manner, such as temporal
RF shape (dynamics), spontaneous activity, and direction selectivity. These
observations identify the extent of functional remodeling in the retina following
rod death but before cone loss. They also indicate new potential challenges to
restoring normal vision by replacing lost rod photoreceptors.NEW & NOTEWORTHY
This study provides novel and therapeutically relevant insights to retinal
function following rod death but before cone death. To determine changes in
retinal output, we used a large-scale multielectrode array to simultaneously
record from hundreds of retinal ganglion cells (RGCs). These recordings of large
scale neural activity revealed that following the death of all rods, functionally
distinct RGCs remain. However, the receptive field properties and spontaneous
activity of these RGCs are altered in a cell type-specific manner.
PMID- 28424301
TI - Patient confidentiality and autonomy: how do we account for coercive control?
PMID- 28424302
TI - Assessing the safety culture of care homes: a multimethod evaluation of the
adaptation, face validity and feasibility of the Manchester Patient Safety
Framework.
AB - BACKGROUND: Understanding the cultural characteristics of healthcare
organisations is widely recognised to be an important component of patient
safety. A growing number of vulnerable older people are living in care homes but
little attention has been paid to safety culture in this sector. In this study,
we aimed to adapt the Manchester Patient Safety Framework (MaPSaF), a commonly
used tool in the health sector, for use in care homes and then to test its face
validity and preliminary feasibility as a tool for developing a better
understanding of safety culture in the sector. METHODS: As part of a wider
improvement programme to reduce the prevalence of common safety incidents among
residents in 90 care homes in England, we adapted MaPSaF and carried out a
multimethod participatory evaluation of its face validity and feasibility for
care home staff. Data were collected using participant observation, interviews,
documentary analysis and a survey, and were analysed thematically. RESULTS:
MaPSaF required considerable adaptation in terms of its length, language and
content in order for it to be perceived to be acceptable and useful to care home
staff. The changes made reflected differences between the health and care home
sectors in terms of the local context and wider policy environment, and the
expectations, capacity and capabilities of the staff. Based on this preliminary
study, the adapted tool, renamed 'Culture is Key', appears to have reasonable
face validity and, with adequate facilitation, it is usable by front-line staff
and useful in raising their awareness about safety issues. CONCLUSIONS: 'Culture
is Key' is a new tool which appears to have acceptable face validity and
feasibility to be used by care home staff to deepen their understanding of the
safety culture of their organisations and therefore has potential to contribute
to improving care for vulnerable older people.
PMID- 28424303
TI - Distribution of genotype network sizes in sequence-to-structure genotype
phenotype maps.
AB - An essential quantity to ensure evolvability of populations is the navigability
of the genotype space. Navigability, understood as the ease with which
alternative phenotypes are reached, relies on the existence of sufficiently large
and mutually attainable genotype networks. The size of genotype networks (e.g.
the number of RNA sequences folding into a particular secondary structure or the
number of DNA sequences coding for the same protein structure) is astronomically
large in all functional molecules investigated: an exhaustive experimental or
computational study of all RNA folds or all protein structures becomes impossible
even for moderately long sequences. Here, we analytically derive the distribution
of genotype network sizes for a hierarchy of models which successively
incorporate features of increasingly realistic sequence-to-structure genotype
phenotype maps. The main feature of these models relies on the characterization
of each phenotype through a prototypical sequence whose sites admit a variable
fraction of letters of the alphabet. Our models interpolate between two limit
distributions: a power-law distribution, when the ordering of sites in the
prototypical sequence is strongly constrained, and a lognormal distribution, as
suggested for RNA, when different orderings of the same set of sites yield
different phenotypes. Our main result is the qualitative and quantitative
identification of those features of sequence-to-structure maps that lead to
different distributions of genotype network sizes.
PMID- 28424304
TI - Giant axonal neuropathy alters the structure of keratin intermediate filaments in
human hair.
AB - Giant axonal neuropathy (GAN) follows an autosomal recessive genetic inheritance
and impedes the peripheral and central nervous system due to axonal swellings
that are packed with neurofilaments. The patients display a number of phenotypes,
including hypotonia, muscle weakness, decreased reflexes, ataxia, seizures,
intellectual disability, pale skin and often curled hair. We used X-ray
diffraction and tensile testing to determine potential changes to the structure
of keratin intermediate filaments (IFs) in the hair of patients with GAN. A
statistically significant decrease in the 47 and the 27 A diffraction signals
were observed. Tensile tests determined that the hair was slightly stiffer,
stronger and more extensible in GAN patients. These results suggest that the
structure of keratin IFs in hair is altered in GAN, and the findings are
compatible with an increased positional disorder of the keratin tetramers within
the hair fibres.
PMID- 28424306
TI - Sociable crayfish get drunk more easily than loners.
PMID- 28424305
TI - Numerical simulation of haemodynamics and low-density lipoprotein transport in
the rabbit aorta and their correlation with atherosclerotic plaque thickness.
AB - Two mechanisms of shear stress and mass transport have been recognized to play an
important role in the development of localized atherosclerosis. However, their
relationship and roles in atherogenesis are still obscure. It is necessary to
investigate quantitatively the correlation among low-density lipoproteins (LDL)
transport, haemodynamic parameters and plaque thickness. We simulated blood flow
and LDL transport in rabbit aorta using computational fluid dynamics and
evaluated plaque thickness in the aorta of a high-fat-diet rabbit. The numerical
results show that regions with high luminal LDL concentration tend to have
severely negative haemodynamic environments (HEs). However, for regions with
moderately and slightly high luminal LDL concentration, the relationship between
LDL concentration and the above haemodynamic indicators is not clear cut. Point
by-point correlation with experimental results indicates that severe
atherosclerotic plaque corresponds to high LDL concentration and seriously
negative HEs, less severe atherosclerotic plaque is related to either moderately
high LDL concentration or moderately negative HEs, and there is almost no
atherosclerotic plaque in regions with both low LDL concentration and positive
HEs. In conclusion, LDL distribution is closely linked to blood flow transport,
and the synergetic effects of luminal surface LDL concentration and wall shear
stress-based haemodynamic indicators may determine plaque thickness.
PMID- 28424308
TI - Spinner dolphin SCUBA tanks develop no faster.
PMID- 28424307
TI - Archer fish jump as well as shoot.
PMID- 28424309
TI - Painkillers relieve zebrafish larvae discomfort.
PMID- 28424310
TI - Heart rate regulation in diving sea lions: the vagus nerve rules.
AB - Recent publications have emphasized the potential generation of morbid cardiac
arrhythmias secondary to autonomic conflict in diving marine mammals. Such
conflict, as typified by cardiovascular responses to cold water immersion in
humans, has been proposed to result from exercise-related activation of cardiac
sympathetic fibers to increase heart rate, combined with depth-related changes in
parasympathetic tone to decrease heart rate. After reviewing the marine mammal
literature and evaluating heart rate profiles of diving California sea lions
(Zalophus californianus), we present an alternative interpretation of heart rate
regulation that de-emphasizes the concept of autonomic conflict and the risk of
morbid arrhythmias in marine mammals. We hypothesize that: (1) both the
sympathetic cardiac accelerator fibers and the peripheral sympathetic vasomotor
fibers are activated during dives even without exercise, and their activities are
elevated at the lowest heart rates in a dive when vasoconstriction is maximal,
(2) in diving animals, parasympathetic cardiac tone via the vagus nerve dominates
over sympathetic cardiac tone during all phases of the dive, thus producing the
bradycardia, (3) adjustment in vagal activity, which may be affected by many
inputs, including exercise, is the primary regulator of heart rate and heart rate
fluctuations during diving, and (4) heart beat fluctuations (benign arrhythmias)
are common in marine mammals. Consistent with the literature and with these
hypotheses, we believe that the generation of morbid arrhythmias because of
exercise or stress during dives is unlikely in marine mammals.
PMID- 28424311
TI - Mechanics of the thorax in flies.
AB - Insects represent more than 60% of all multicellular life forms, and are easily
among the most diverse and abundant organisms on earth. They evolved functional
wings and the ability to fly, which enabled them to occupy diverse niches.
Insects of the hyper-diverse orders show extreme miniaturization of their body
size. The reduced body size, however, imposes steep constraints on flight
ability, as their wings must flap faster to generate sufficient forces to stay
aloft. Here, we discuss the various physiological and biomechanical adaptations
of the thorax in flies which enabled them to overcome the myriad constraints of
small body size, while ensuring very precise control of their wing motion. One
such adaptation is the evolution of specialized myogenic or asynchronous muscles
that power the high-frequency wing motion, in combination with neurogenic or
synchronous steering muscles that control higher-order wing kinematic patterns.
Additionally, passive cuticular linkages within the thorax coordinate fast and
yet precise bilateral wing movement, in combination with an actively controlled
clutch and gear system that enables flexible flight patterns. Thus, the study of
thoracic biomechanics, along with the underlying sensory-motor processing, is
central in understanding how the insect body form is adapted for flight.
PMID- 28424312
TI - Archer fish jumping prey capture: kinematics and hydrodynamics.
AB - Smallscale archer fish, Toxotes microlepis, are best known for spitting jets of
water to capture prey, but also hunt by jumping out of the water to heights of up
to 2.5 body lengths. In this study, high-speed imaging and particle image
velocimetry were used to characterize the kinematics and hydrodynamics of this
jumping behavior. Jumping used a set of kinematics distinct from those of in
water feeding strikes and was segmented into three phases: (1) hovering to sight
prey at the surface, (2) rapid upward thrust production and (3) gliding to the
prey once out of the water. The number of propulsive tail strokes positively
correlated with the height of the bait, as did the peak body velocity observed
during a jump. During the gliding stage, the fish traveled ballistically; the
kinetic energy when the fish left the water balanced with the change in potential
energy from water exit to the maximum jump height. The ballistic estimate of the
mechanical energy required to jump was comparable with the estimated mechanical
energy requirements of spitting a jet with sufficient momentum to down prey and
subsequently pursuing the prey in water. Particle image velocimetry showed that,
in addition to the caudal fin, the wakes of the anal, pectoral and dorsal fins
were of nontrivial strength, especially at the onset of thrust production. During
jump initiation, these fins were used to produce as much vertical acceleration as
possible given the spatial constraint of starting directly at the water's surface
to aim.
PMID- 28424313
TI - Reduction in activity by noxious chemical stimulation is ameliorated by immersion
in analgesic drugs in zebrafish.
AB - Research has recently demonstrated that larval zebrafish show similar molecular
responses to nociception to those of adults. Our study explored whether
unprotected larval zebrafish exhibited altered behaviour after exposure to
noxious chemicals and screened a range of analgesic drugs to determine their
efficacy to reduce these responses. This approach aimed to validate larval
zebrafish as a reliable replacement for adults as well as providing a high
throughput means of analysing behavioural responses. Zebrafish at 5 days post
fertilization were exposed to known noxious stimuli: acetic acid (0.01%, 0.1% and
0.25%) and citric acid (0.1%, 1% and 5%). The behavioural response of each was
recorded and analysed using novel tracking software that measures time spent
active in 25 larvae at one time. Subsequently, the efficacy of aspirin,
lidocaine, morphine and flunixin as analgesics after exposure to 0.1% acetic acid
was tested. Larvae exposed to 0.1% and 0.25% acetic acid spent less time active,
whereas those exposed to 0.01% acetic acid and 0.1-5% citric acid showed an
increase in swimming activity. Administration of 2.5 mg l-1 aspirin, 5 mg l-1
lidocaine and 48 mg l-1 morphine prevented the behavioural changes induced by
acetic acid. These results suggest that larvae respond to a noxious challenge in
a similar way to adult zebrafish and other vertebrates and that the effect of
nociception on activity can be ameliorated by using analgesics. Therefore,
adopting larval zebrafish could represent a direct replacement of a protected
adult fish with a non-protected form in pain- and nociception-related research.
PMID- 28424314
TI - Muscle biochemistry of a pelagic delphinid (Stenella longirostris longirostris):
insight into fishery-induced separation of mothers and calves.
AB - The length of time required for postnatal maturation of the locomotor muscle
(longissimus dorsi) biochemistry [myoglobin (Mb) content and buffering capacity]
in marine mammals typically varies with nursing duration, but it can be
accelerated by species-specific behavioral demands, such as deep-diving and sub
ice transit. We examined how the swimming demands of a pelagic lifestyle
influence postnatal maturation of Mb and buffering capacity in spinner dolphins
(Stenella longirostris longirostris). Mb content of newborn (1.16+/-0.07 g Mb per
100 g wet muscle mass, n=6) and juvenile (2.77+/-0.22 g per 100 g, n=4) spinner
dolphins were only 19% and 46% of adult levels (6.00+/-0.74 g per 100 g, n=6),
respectively. At birth, buffering capacity was 52.70+/-4.48 slykes (n=6) and
increased to 78.53+/-1.91 slykes (n=6) once a body length of 141 cm was achieved,
representing 1.6- to 2.0-year-old dolphins. Based on the age of weaning (1.3-1.6
years post-partum), muscle maturation occurred just after weaning as described
for coastal bottlenose dolphins (Tursiops truncatus). Thus, a pelagic lifestyle
does not promote rapid maturation of muscle biochemistry. Rather, it promotes
enhanced muscle biochemistry: newborn and adult spinner dolphins had four- and
two-times greater Mb contents than newborn and adult bottlenose dolphins,
respectively. Indeed, adult levels rivaled those of deep-diving cetaceans.
Nonetheless, the relatively underdeveloped muscle biochemistry of calves likely
contributes to documented mother-calf separations for spinner dolphins chased by
the tuna purse-seine fishery.
PMID- 28424315
TI - Prior social experience affects the behavioral and neural responses to acute
alcohol in juvenile crayfish.
AB - The effects of alcohol on society can be devastating, both as an immediate
consequence of acute intoxication and as a powerful drug of abuse. However, the
neurocellular mechanisms of alcohol intoxication are still elusive, partly
because of the complex interactions between alcohol and nervous system function.
We found that juvenile crayfish are behaviorally sensitive to acute alcohol
exposure and progress through stages that are strikingly similar to those of most
other intoxicated organisms. Most surprisingly, we found that the social history
of the animals significantly modified the acute effects of alcohol. Crayfish
taken from a rich social environment became intoxicated more rapidly than animals
that were socially isolated before alcohol exposure. In addition, we found that
the modulation of intoxicated behaviors by prior social experience was paralleled
on the level of individual neurons. These results significantly improve our
understanding of the mechanisms underlying the interplay between social
experience, alcohol intoxication and nervous system function.
PMID- 28424316
TI - Correction: Lombard effect onset times reveal the speed of vocal plasticity in a
songbird.
PMID- 28424317
TI - The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and
social anxiety in a healthy population.
AB - The neurohormone oxytocin plays a central role in human social behaviour and
cognition, and oxytocin dysregulation may contribute to psychiatric disorders.
However, genetic factors influencing individual variation in the oxytocinergic
system remain poorly understood. We genotyped 169 healthy adults for a functional
polymorphism in GTF2I (general transcription factor II-I), a gene associated with
high prosociality and reduced social anxiety in Williams syndrome, a condition
reported to involve high oxytocin levels and reactivity. Participants' salivary
oxytocin levels were measured before and after watching a validated empathy
inducing video. Oxytocin reactivity, defined as pre- to post-video percentage
change in salivary oxytocin, varied substantially and significantly between
individuals with different GTF2I genotypes, with, additionally, a trend towards
an interaction between genotype and sex. Individuals with more oxytocin-reactive
genotypes also reported significantly lower social anxiety. These findings
suggest a model whereby GTF2I has a continuum of effects on human sociality, from
the extreme social phenotypes and oxytocin dysregulation associated with gene
deletion in Williams syndrome, to individual differences in oxytocin reactivity
and sociality associated with common polymorphisms in healthy populations.
PMID- 28424318
TI - Infection dynamics of Mycoplasma hyorhinis in three commercial pig populations.
AB - Mycoplasma hyorhinis is one of the causative agents of polyserositis and
arthritis inpostweaning pigs. Knowledge regarding colonisation frequency and age
distribution inmodern pig production is lacking. The objective of this study was
to estimate the prevalenceof M hyorhinis colonisation in different age groups
across three commercial pig populations.Nasal swabs were collected from sows,
piglets and nursery pigs of different ages. Oral fluidswere collected from
nursery pigs. Necropsies were performed to assess the presence ofM hyorhinis
associated disease. M hyorhinis was detected in 5/60 sows in herd A, 3/60 inherd
B and none in herd C. In herd A and B, the prevalence was low in preweaning
piglets(~8 per cent) and high in postweaning pigs (~98 per cent). A total of 7/8
oral fluids testedPCR positive in herds A and B, while 1/8 tested positive in
herd C. In herd C, the preweaningand postweaning prevalence was low. In herds A
and B, necropsied pigs had polyserositislesions where M hyorhinis was detected by
PCR. This study showed that prevalence ofM hyorhinis colonisation varies with pig
age and across farms. Information generated will aidin the design and
implementation of control and prevention strategies.
PMID- 28424319
TI - A survey on antimicrobial resistant Escherichia coli isolated from unpasteurised
cows' milk in Northern Ireland.
PMID- 28424321
TI - The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch
activity to modulate germline stem cell niche formation.
AB - The developmental signalling protein Notch can be proteolytically activated
following ligand-interaction at the cell surface, or can be activated
independently of its ligands, following Deltex (Dx)-induced Notch endocytosis and
trafficking to the lysosomal membrane. The means by which different pools of
Notch are directed towards these alternative outcomes remains poorly understood.
We found that the Drosophila ZO-1 protein Polychaetoid (Pyd) suppresses
specifically the Dx-induced form of Notch activation both in vivo and in cell
culture assays. In vivo we confirmed the physiological relevance and direction of
the Pyd/Dx interaction by showing that the expanded ovary stem cell niche
phenotypes of pyd mutants require the presence of functional Dx and other
components that are specific to the Dx-induced Notch activation mechanism. In S2
cells we found that Pyd can form a complex with Dx and Notch at the cell surface
and reduce Dx-induced Notch endocytosis. Similar to other known activities of ZO
1 family proteins, the action of Pyd on Dx-induced endocytosis and signalling was
found to be cell density dependent. Thus, together, our results suggest an
alternative means by which external cues can tune Notch signalling through Pyd
regulation of Dx-induced Notch trafficking.
PMID- 28424322
TI - Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS): A Rare but Potentially
Treatable Condition.
AB - Kaposi sarcoma inflammatory cytokine syndrome (KICS) is a newly-described
condition affecting individuals who are HIV-positive and are infected with human
herpesvirus 8 (HHV-8). This is a syndrome that in some ways mimics severe sepsis
with associated acute respiratory distress syndrome, possibly requiring a
ventilator and vasopressor support. However, unlike severe sepsis, antibiotics
provide no benefit. Management of KICS has not been fully elucidated because of
its high mortality rate. However, the syndrome has been successfully treated in
some cases with immunomodulatory therapy. It is crucial for oncologists to be
able to recognize this syndrome and to institute the appropriate therapy. The
Oncologist 2017;22:623-625.
PMID- 28424320
TI - TRPA1 expression and its functional activation in rodent cortex.
AB - TRPA1 is a non-selective cation channel involved in pain sensation and neurogenic
inflammation. Although TRPA1 is well established in a number of organs including
the nervous system, its presence and function in the mammalian cortex remains
unclear. Here, we demonstrate the expression of TRPA1 in rodent somatosensory
cortex through immunostaining and investigate its functional activation by whole
cell electrophysiology, Ca2+ imaging and two-photon photoswitching. Application
of TRPA1 agonist (AITC) and antagonist (HC-030031) produced significant
modulation of activity in layer 5 (L5) pyramidal neurons in both rats and mice;
AITC increased intracellular Ca2+ concentrations and depolarized neurons, and
both effects were blocked by HC-030031. These modulations were absent in the
TRPA1 knockout mice. Next, we used optovin, a reversible photoactive molecule, to
activate TRPA1 in individual L5 neurons of rat cortex. Optical control of
activity was established by applying a tightly focused femtosecond-pulsed laser
to optovin-loaded neurons. Light application depolarized neurons (n = 17) with
the maximal effect observed at lambda = 720 nm. Involvement of TRPA1 was further
confirmed by repeating the experiment in the presence of HC-030031, which
diminished the light modulation. These results demonstrate the presence of TRPA1
in L5 pyramidal neurons and introduce a highly specific approach to further
understand its functional significance.
PMID- 28424323
TI - Dosing Three-Drug Combinations That Include Targeted Anti-Cancer Agents: Analysis
of 37,763 Patients.
AB - BACKGROUND: Combining targeted and cytotoxic agents has the potential to improve
efficacy and attenuate resistance for metastatic cancer. Information regarding
safe starting doses for clinical trials of novel three-drug combinations is
lacking. MATERIALS AND METHODS: Published phase I-III adult oncology clinical
trials of three-drug combinations involving a targeted agent were identified by
PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was
calculated to compare the dose used in combination to the single agent
recommended dose: (U.S. Food and Drug Administration-approved/recommended phase
II dose/maximum tolerated dose). The additive dose percentage was the sum of the
dose percentages for each drug in the combination. RESULTS: A total of 37,763
subjects and 243 drug combinations were included. Only 28% of studies could give
each of the three agents at 100%. For combinations involving two targeted agents
and a cytotoxic agent, the lowest starting additive dose percentage was 133%,
which increased to 250% if two antibodies were included. For combinations of one
targeted agent and two cytotoxic agents, the lowest additive safe dose percentage
was 137%. When both cytotoxic agents were held at 100%, as occurred in 56% of
studies (which generally used cytotoxic doublets with known combination safety
dosing), the lowest safe dose percentage was 225% (providing that a histone
deacetylase inhibitor was not the targeted agent). CONCLUSION: These findings
serve as a safe starting point for dosing novel three-drug combinations involving
a targeted agent in clinical trials and practice. The Oncologist 2017;22:576-584
IMPLICATIONS FOR PRACTICE: Targeted and cytotoxic drug combinations can improve
efficacy and overcome resistance. More knowledge of safe starting doses would
facilitate use of combinations in clinical trials and practice. Analysis of
37,763 subjects (243 combinations) showed three drugs could be safely
administered, but less than 30% of combinations could include all three drugs at
full dose. Dose reductions to 45% of the dose of each single agent may be
required. Combinations involving two antibodies required fewer dose reductions,
and the use of established cytotoxic doublets made initial dose assignment
easier.
PMID- 28424324
TI - Preventing Venous Thromboembolism in Ambulatory Cancer Patients: The ONKOTEV
Study.
AB - BACKGROUND: The efficacy of risk model scores to predict venous thromboembolism
(VTE) in ambulatory cancer patients is under investigation, aiming to stratify on
an individual risk basis the subset of the cancer population that could mostly
benefit from primary thromboprophylaxis. MATERIALS AND METHODS: We prospectively
assessed 843 patients with active cancers, collecting clinical and laboratory
data. We screened all the patients with a duplex ultrasound (B-mode imaging and
Doppler waveform analysis) of the upper and lower limbs to evaluate the right
incidence of VTE (both asymptomatic and symptomatic). The efficacy of the
existing Khorana risk model in preventing VTE was also explored in our
population. Several risk factors associated with VTE were analyzed, leading to
the construction of a risk model. The Fine and Gray model was used to account for
death as a competing risk in the derivation of the new model. RESULTS: The risk
factors significantly associated with VTE at univariate analysis and further
confirmed in the multivariate analysis, after bootstrap validation, were the
presence of metastatic disease, the compression of vascular/lymphatic structures
by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent
receiving operating characteristic (ROC) curve analysis showed a significant
improvement in the area under the curve of the new score over the Khorana model
at 3 months (71.9% vs. 57.9%, p = .001), 6 months (75.4% vs. 58.6%, p < .001),
and 12 months (69.8% vs. 58.3%, p = .014). CONCLUSION: ONKOTEV score steps into
history of cancer-related-VTE as a promising tool to drive the decision about
primary prophylaxis in cancer outpatients. The validation represents the goal of
the prospective ONKOTEV-2 study, endorsed and approved by the European
Organization for Research and Treatment of Cancer Young Investigators Program.
The Oncologist 2017;22:601-608 IMPLICATIONS FOR PRACTICE: Preventing venous
thromboembolism in cancer outpatients with a risk model score will drive
physicians' decision of starting thromboprophylaxis in high-risk patients.
PMID- 28424325
TI - FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive
Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.
AB - : Until recently in the United States, no products were approved for second-line
treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and
Drug Administration approved atezolizumab for the treatment of patients with
locally advanced or metastatic urothelial carcinoma whose disease progressed
during or following platinum-containing chemotherapy or within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and
represents the first approved product directed against PD-L1. This accelerated
approval was based on results of a single-arm trial in 310 patients with locally
advanced or metastatic urothelial carcinoma who had disease progression after
prior platinum-containing chemotherapy. Patients received atezolizumab 1,200 mg
intravenously every 3 weeks until disease progression or unacceptable toxicity.
Key efficacy measures were objective response rate (ORR), as assessed by
Independent Review per RECIST 1.1, and duration of response (DoR). With a median
follow-up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all
treated patients. Median DoR was not reached and response durations ranged from
2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response
for >= 6 months. The most common adverse reactions (>=20%) were fatigue,
decreased appetite, nausea, urinary tract infection, pyrexia, and constipation.
Infection and immune-related adverse events also occurred, including pneumonitis,
hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit-risk
assessment was favorable to support accelerated approval. The observed clinical
benefits need to be verified in confirmatory trial(s). IMPLICATIONS FOR PRACTICE:
This accelerated approval of atezolizumab for second-line use in advanced
urothelial carcinoma provides patients with an effective, novel treatment option
for the management of their disease. This represents the first immunotherapy
approved in this disease setting.
PMID- 28424326
TI - Anti-tau antibody administration increases plasma tau in transgenic mice and
patients with tauopathy.
AB - Tauopathies are a group of disorders in which the cytosolic protein tau
aggregates and accumulates in cells within the brain, resulting in
neurodegeneration. A promising treatment being explored for tauopathies is
passive immunization with anti-tau antibodies. We previously found that
administration of an anti-tau antibody to human tau transgenic mice increased the
concentration of plasma tau. We further explored the effects of administering an
anti-tau antibody on plasma tau. After peripheral administration of an anti-tau
antibody to human patients with tauopathy and to mice expressing human tau in the
central nervous system, there was a dose-dependent increase in plasma tau. In
mouse plasma, we found that tau had a short half-life of 8 min that increased to
more than 3 hours after administration of anti-tau antibody. As tau transgenic
mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid
tau decreased. Administration of anti-tau antibody to tau transgenic mice that
had decreased brain soluble tau and interstitial fluid tau resulted in an
increase in plasma tau, but this increase was less than that observed in tau
transgenic mice without these brain changes. Tau transgenic mice subjected to
acute neuronal injury using 3-nitropropionic acid showed increased interstitial
fluid tau and plasma tau. These data suggest that peripheral administration of an
anti-tau antibody results in increased plasma tau, which correlates with the
concentration of extracellular and soluble tau in the brain.
PMID- 28424328
TI - Toward off-the-shelf adoptive T cell therapies.
AB - Artificial thymic organoids may enable more efficient engineered T cell
production for immunotherapy.
PMID- 28424327
TI - RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and
immune-mediated tissue injury.
AB - The molecular pathways that regulate the tissue repair function of type I
interferon (IFN-I) during acute tissue damage are poorly understood. We describe
a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute
tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein
(MAVS) were more sensitive to total body irradiation- and chemotherapy-induced
intestinal barrier damage. These mice developed worse graft-versus-host disease
(GVHD) in a preclinical model of allogeneic hematopoietic stem cell
transplantation (allo-HSCT) than did wild-type mice. This phenotype was not
associated with changes in the intestinal microbiota but was associated with
reduced gut epithelial integrity. Conversely, targeted activation of the RIG-I
pathway during tissue injury promoted gut barrier integrity and reduced GVHD.
Recombinant IFN-I or IFN-I expression induced by RIG-I promoted growth of
intestinal organoids in vitro and production of the antimicrobial peptide
regenerating islet-derived protein 3 gamma (RegIIIgamma). Our findings were not
confined to RIG-I/MAVS signaling because targeted engagement of the STING
(stimulator of interferon genes) pathway also protected gut barrier function and
reduced GVHD. Consistent with this, STING-deficient mice suffered worse GVHD
after allo-HSCT than did wild-type mice. Overall, our data suggest that
activation of either RIG-I/MAVS or STING pathways during acute intestinal tissue
injury in mice resulted in IFN-I signaling that maintained gut epithelial barrier
integrity and reduced GVHD severity. Targeting these pathways may help to prevent
acute intestinal injury and GVHD during allogeneic transplantation.
PMID- 28424329
TI - A paternal diet for offspring success?
AB - Supplementation of the diet of male mice with methyl donors, such as methionine
and folic acid, prior to mating impaired learning, memory, and metabolic
functions in the offspring.
PMID- 28424330
TI - Combination of an oncolytic virus with PD-L1 blockade keeps cancer in check.
AB - An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade
significantly reduces tumor burden and improves survival in murine cancer models.
PMID- 28424331
TI - Filtering more than light in the developing retina.
AB - Restricting transcytosis is essential for blood-retinal barrier formation.
PMID- 28424333
TI - Clinical chemoproteomics-Opportunities and obstacles.
AB - Chemoproteomics is the large-scale study of proteins using chemical methods.
Although chemoproteomic techniques are becoming commonplace in preclinical
research, few examples have found clinical utility. We explore the prospects for
advancing chemoproteomics into the clinical setting to understand drug-target
interactions and to identify new therapeutically relevant targets.
PMID- 28424335
TI - A Conversation with Raghu Kalluri.
PMID- 28424332
TI - Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.
AB - Exome and whole-genome sequencing are becoming increasingly routine approaches in
Mendelian disease diagnosis. Despite their success, the current diagnostic rate
for genomic analyses across a variety of rare diseases is approximately 25 to
50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA
seq)] as a complementary diagnostic tool in a cohort of 50 patients with
genetically undiagnosed rare muscle disorders. We describe an integrated approach
to analyze patient muscle RNA-seq, leveraging an analysis framework focused on
the detection of transcript-level changes that are unique to the patient compared
to more than 180 control skeletal muscle samples. We demonstrate the power of RNA
seq to validate candidate splice-disrupting mutations and to identify splice
altering variants in both exonic and deep intronic regions, yielding an overall
diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo
intronic mutation in COL6A1 that results in a dominantly acting splice-gain
event, disrupting the critical glycine repeat motif of the triple helical domain.
We identify this pathogenic variant in a total of 27 genetically unsolved
patients in an external collagen VI-like dystrophy cohort, thus explaining
approximately 25% of patients clinically suggestive of having collagen VI
dystrophy in whom prior genetic analysis is negative. Overall, this study
represents a large systematic application of transcriptome sequencing to rare
disease diagnosis and highlights its utility for the detection and interpretation
of variants missed by current standard diagnostic approaches.
PMID- 28424334
TI - Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue
defective wound healing in mice.
AB - Excessive production of inflammatory chemokines can cause chronic inflammation
and thus impair cutaneous wound healing. Capturing chemokine signals using wound
dressing materials may offer powerful new treatment modalities for chronic
wounds. Here, a modular hydrogel based on end-functionalized star-shaped
polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG)
heparin was customized for maximal chemokine sequestration. The material is shown
to effectively scavenge the inflammatory chemokines MCP-1 (monocyte
chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1alpha (macrophage
inflammatory protein-1alpha) and MIP-1beta (macrophage inflammatory protein
1beta) in wound fluids from patients suffering from chronic venous leg ulcers and
to reduce the migratory activity of human monocytes and polymorphonuclear
neutrophils. In an in vivo model of delayed wound healing (db/db mice), starPEG
GAG hydrogels outperformed the standard-of-care product Promogran with respect to
reduction of inflammation, as well as increased granulation tissue formation,
vascularization, and wound closure.
PMID- 28424336
TI - A Conversation with Karen Cichowski.
PMID- 28424337
TI - Physical and Chemical Gradients in the Tumor Microenvironment Regulate Tumor Cell
Invasion, Migration, and Metastasis.
AB - Cancer metastasis requires the invasion of tumor cells into the stroma and the
directed migration of tumor cells through the stroma toward the vasculature and
lymphatics where they can disseminate and colonize secondary organs. Physical and
biochemical gradients that form within the primary tumor tissue promote tumor
cell invasion and drive persistent migration toward blood vessels and the
lymphatics to facilitate tumor cell dissemination. These microenvironment cues
include hypoxia and pH gradients, gradients of soluble cues that induce
chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to
the concentration, organization, and stiffness of the extracellular matrix that
produce haptotactic, alignotactic, and durotactic gradients. These gradients form
through dynamic interactions between the tumor cells and the resident
fibroblasts, adipocytes, nerves, endothelial cells, infiltrating immune cells,
and mesenchymal stem cells. Malignant progression results from the integrated
response of the tumor to these extrinsic physical and chemical cues. Here, we
first describe how these physical and chemical gradients develop, and we discuss
their role in tumor progression. We then review assays to study these gradients.
We conclude with a discussion of clinical strategies used to detect and inhibit
these gradients in tumors and of new intervention opportunities. Clarifying the
role of these gradients in tumor evolution offers a unique approach to target
metastasis.
PMID- 28424338
TI - A Conversation with David Lyden.
PMID- 28424339
TI - Discovery of Double-Stranded Genomic DNA in Circulating Exosomes.
AB - It is becoming increasingly clear that small vesicles released from cells
(extracellular vesicles [EVs]) represent a heterogeneous population implicated in
cell-to-cell communication. The classifications and nomenclature of EVs are
evolving as enrichment strategies and specific characteristics are being
unraveled. At present, physical properties of EVs-namely, size, shape, and
density-are often used to identify subpopulations of EVs. A distinct group of
EVs, termed exosomes, largely defined by their small size (~40-150 nm) and
proposed subcellular origin, has been extensively studied in several aspects of
cancer biology. Exosomes are implicated in modulating behavior of cancer cells as
well as the immune and angiogenic responses in tumors, possibly contributing to
cancer progression locally and systemically. Most intriguingly, the nucleic acid
content of exosomes has been proposed to play a role in oncogenic transformation
and transfer of cancer-specific genome to promote cancer pathogenesis. Here, we
specifically focus on the discovery of exosomal DNA, studies related to the
origin of genomic DNA in exosomes, and its utility in cancer diagnosis and
disease monitoring.
PMID- 28424340
TI - A Conversation with Valerie Weaver.
PMID- 28424341
TI - Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome.
AB - The structural and functional basis of the genome is provided by the three
dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer
elements and promoter regions are brought into close spatial proximity to ensure
proper, cell type-specific gene expression. In cancer, genetic and epigenetic
processes can deregulate the transcriptional program. To investigate whether the
3D chromatin state is also disrupted in cancer we performed Hi-C chromosome
conformation sequencing in normal and prostate cancer cells and compared the
chromatin interaction maps with changes to the genome and epigenome. Notably, we
find that additional topologically associated domain (TAD) boundaries are formed
in cancer cells resulting in smaller TADs and altered gene expression profiles.
The new TAD boundaries are commonly associated with copy-number changes observed
in the cancer genome. We also identified new cancer-specific chromatin loops
within TADs that are enriched for enhancers and promoters. Finally, we find that
many of the long-range epigenetically silenced (LRES) and long-range
epigenetically active (LREA) regions in cancer are characterized by differential
chromatin interactions. Together our data provide a new insight into charting
alterations in higher-order structure and the relationship with genetic,
epigenetic, and transcriptional changes across the cancer genome.
PMID- 28424342
TI - Individual variation in local interaction rules can explain emergent patterns of
spatial organization in wild baboons.
AB - Researchers have long noted that individuals occupy consistent spatial positions
within animal groups. However, an individual's position depends not only on its
own behaviour, but also on the behaviour of others. Theoretical models of
collective motion suggest that global patterns of spatial assortment can arise
from individual variation in local interaction rules. However, this prediction
remains untested. Using high-resolution GPS tracking of members of a wild baboon
troop, we identify consistent inter-individual differences in within-group
spatial positioning. We then apply an algorithm that identifies what number of
conspecific group members best predicts the future location of each individual
(we call this the individual's neighbourhood size) while the troop is moving. We
find clear variation in the most predictive neighbourhood size, and this
variation relates to individuals' propensity to be found near the centre of their
group. Using simulations, we show that having different neighbourhood sizes is a
simple candidate mechanism capable of linking variation in local individual
interaction rules-in this case how many conspecifics an individual interacts with
to global patterns of spatial organization, consistent with the patterns we
observe in wild primates and a range of other organisms.
PMID- 28424343
TI - Interactive effects of temperature, food and skeletal mineralogy mediate
biological responses to ocean acidification in a widely distributed bryozoan.
AB - Marine invertebrates with skeletons made of high-magnesium calcite may be
especially susceptible to ocean acidification (OA) due to the elevated solubility
of this form of calcium carbonate. However, skeletal composition can vary
plastically within some species, and it is largely unknown how concurrent changes
in multiple oceanographic parameters will interact to affect skeletal mineralogy,
growth and vulnerability to future OA. We explored these interactive effects by
culturing genetic clones of the bryozoan Jellyella tuberculata (formerly
Membranipora tuberculata) under factorial combinations of dissolved carbon
dioxide (CO2), temperature and food concentrations. High CO2 and cold temperature
induced degeneration of zooids in colonies. However, colonies still maintained
high growth efficiencies under these adverse conditions, indicating a
compensatory trade-off whereby colonies degenerate more zooids under stress,
redirecting energy to the growth and maintenance of new zooids. Low-food
concentration and elevated temperatures also had interactive effects on skeletal
mineralogy, resulting in skeletal calcite with higher concentrations of
magnesium, which readily dissolved under high CO2 For taxa that weakly regulate
skeletal magnesium concentration, skeletal dissolution may be a more widespread
phenomenon than is currently documented and is a growing concern as oceans
continue to warm and acidify.
PMID- 28424344
TI - Mutualistic cleaner fish maintains high escape performance despite privileged
relationship with predators.
AB - Predatory reef fishes regularly visit mutualistic cleaner fish (Labroides
dimidiatus) to get their ectoparasites removed but show no interest in eating
them. The concept of compensated trait loss posits that characters can be lost if
a mutualistic relationship reduces the need for a given trait. Thus, selective
pressures on escape performance might have relaxed in L. dimidiatus due to its
privileged relationship with predators. However, the cost of failing to escape a
predatory strike is extreme even if predation events on cleaners are
exceptionally rare. Additionally, cleaners must escape from non-predatory clients
that regularly punish them for eating mucus instead of parasites. Therefore,
strong escape capabilities might instead be maintained in cleaner fish because
they must be able to flee when in close proximity to predators or dissatisfied
clients. We compared the fast-start escape performance of L. dimidiatus with that
of five closely related wrasse species and found that the mutualistic
relationship that cleaners entertain with predators has not led to reduced escape
performance. Instead, conflicts in cleaning interactions appear to have
maintained selective pressures on this trait, suggesting that compensated trait
loss might only evolve in cases of high interdependence between mutualistic
partners that are not tempted to cheat.
PMID- 28424345
TI - Floaters may buffer the extinction risk of small populations: an empirical
assessment.
AB - The high extinction risk of small populations is commonly explained by reductions
in fecundity and breeder survival associated with demographic and environmental
stochasticity. However, ecological theory suggests that population extinctions
may also arise from reductions in the number of floaters able to replace the lost
breeders. This can be particularly plausible under harsh fragmentation scenarios,
where species must survive as small populations subjected to severe effects of
stochasticity. Using a woodpecker study in fragmented habitats (2004-2016), we
provide here empirical support for the largely neglected hypothesis that floaters
buffer population extirpation risks. After controlling for population size, patch
size and the intrinsic quality of habitat, populations in patches with floaters
had a lower extinction probability than populations in patches without floaters
(0.013 versus 0.131). Floaters, which often replace the lost breeders, were less
likely to occur in small and low-quality patches, showing that population
extirpations may arise from unnoticed reductions in floater numbers in poor
quality habitats. We argue that adequate pools of the typically overlooked
floaters may buffer extirpation risks by reducing the detrimental impacts of
demographic and environmental stochasticity. However, unravelling the influence
of floaters in buffering stochastic effects and promoting population stability
require additional studies in an ample array of species and stochastic scenarios.
PMID- 28424346
TI - The 'male escape hypothesis': sex-biased metamorphosis in response to climatic
drivers in a facultatively paedomorphic amphibian.
AB - Paedomorphosis is a major evolutionary process that bypasses metamorphosis and
allows reproduction in larvae. In newts and salamanders, it can be facultative
with paedomorphs retaining gills and metamorphs dispersing. The evolution of
these developmental processes is thought to have been driven by the costs and
benefits of inhabiting aquatic versus terrestrial habitats. In this context, we
aimed at testing the hypothesis that climatic drivers affect phenotypic
transition and the difference across sexes because sex-ratio is biased in natural
populations. Through a replicated laboratory experiment, we showed that
paedomorphic palmate newts (Lissotriton helveticus) metamorphosed at a higher
frequency when water availability decreased and metamorphosed earlier when
temperature increased in these conditions. All responses were sex-biased, and
males were more prone to change phenotype than females. Our work shows how
climatic variables can affect facultative paedomorphosis and support theoretical
models predicting life on land instead of in water. Moreover, because males
metamorphose and leave water more often and earlier than females, these results,
for the first time, give an experimental explanation for the rarity of male
paedomorphosis (the 'male escape hypothesis') and suggest the importance of sex
in the evolution of paedomorphosis versus metamorphosis.
PMID- 28424347
TI - Long-term fitness consequences of early environment in a long-lived ungulate.
AB - Cohort effects can be a major source of heterogeneity and play an important role
in population dynamics. Silver-spoon effects, when environmental quality at birth
improves future performance regardless of the adult environment, can induce
strong lagged responses on population growth. Alternatively, the external
predictive adaptive response (PAR) hypothesis predicts that organisms will adjust
their developmental trajectory and physiology during early life in anticipation
of expected adult conditions but has rarely been assessed in wild species. We
used over 40 years of detailed individual monitoring of bighorn ewes (Ovis
canadensis) to quantify long-term cohort effects on survival and reproduction. We
then tested both the silver-spoon and the PAR hypotheses. Cohort effects involved
a strong interaction between birth and current environments: reproduction and
survival were lowest for ewes that were born and lived at high population
densities. This interaction, however, does not support the PAR hypothesis because
individuals with matching high-density birth and adult environments had reduced
fitness. Instead, individuals born at high density had overall lower lifetime
fitness suggesting a silver-spoon effect. Early-life conditions can induce long
term changes in fitness components, and their effects on cohort fitness vary
according to adult environment.
PMID- 28424348
TI - Tobacco: a threat to development?
PMID- 28424349
TI - Worldwide news and comment.
PMID- 28424350
TI - Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the
ventral tegmental area and reduction of transcription factor orthodenticle
homeobox 2 expression.
AB - Homozygous tau knockout (Mapt-/-) mice develop age-dependent dopaminergic (DA)
neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA),
supporting an important function of tau in maintaining the survival of midbrain
dopaminergic neurons (mDANs) during aging. However, it remains to be determined
whether the microtubule-associated protein tau regulates the differentiation and
survival of mDANs during embryonic developmental stages. Here, we show that tau
haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/-) pups, but not a
complete loss of tau in the Mapt-/- littermates, led to a significant reduction
of DA neurons in the VTA. This selective loss of DA neurons correlated with a
similar reduction in orthodenticle homeobox 2 (Otx2), which is restricted to VTA
neurons at the postmitotic stage and selectively controls the neurogenesis and
survival of specific neuronal subtypes of VTA. Moreover, the prenatal
developmental cell death in the Mapt+/- VTA specifically increased, and the
expression of microtubule-associated protein (MAP)-1A was significantly up
regulated in the P0 Mapt-/- , but not the Mapt+/- , pups. These results suggest
that tau haploinsufficiency, without the compensation effect of MAP1A, induces
reduction of Otx2 expression, increases prenatal cell death, and accordingly
leads to selective loss of VTA DA neurons in the early postnatal stage. Our
findings highlight the impact of tau haploinsufficiency on the survival of mDANs
and indicate that tau may participate in midbrain development in a dose-dependent
way.-Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang,
G., Li, Y., Jiang, B., Cai, H., Lin, X. Tau haploinsufficiency causes prenatal
loss of dopaminergic neurons in the ventral tegmental area and reduction of
transcription factor orthodenticle homeobox 2 expression.
PMID- 28424351
TI - miR-191 suppresses angiogenesis by activation of NF-kappaB signaling.
AB - MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes.
However, the function of most miRNAs in angiogenesis remains elusive. In this
study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel
development. Transfection of human dermal microvascular endothelial cells with
miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube
formation. Moreover, vascular sprouting of miR-191m-transfected mouse aortic
rings was significantly reduced when compared with controls. Transfection with
miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti- and
proangiogenic activities of miR-191m and -191i were further demonstrated in vivo
Additional molecular biologic analyses revealed that miR-191m activates NF-kappaB
signaling by up-regulating the mRNA expression of p65. miR-191 also increased the
mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of
metalloproteinase-1 and reduced the expression of the proangiogenic factors eNOS
and matrix metalloproteinase-1 and -9. Blockade of NF-kappaB activation with Bay
11-7082 reversed the antiangiogenic effects of miR-191m. These findings indicate
that miR-191 effectively suppresses angiogenesis by activation of the NF-kappaB
signaling pathway.-Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. miR-191
suppresses angiogenesis by activation of NF-kappaB signaling.
PMID- 28424352
TI - Chromatin module inference on cellular trajectories identifies key transition
points and poised epigenetic states in diverse developmental processes.
AB - Changes in chromatin state play important roles in cell fate transitions. Current
computational approaches to analyze chromatin modifications across multiple cell
types do not model how the cell types are related on a lineage or over time. To
overcome this limitation, we developed a method called Chromatin Module INference
on Trees (CMINT), a probabilistic clustering approach to systematically capture
chromatin state dynamics across multiple cell types. Compared to existing
approaches, CMINT can handle complex lineage topologies, capture higher quality
clusters, and reliably detect chromatin transitions between cell types. We
applied CMINT to gain novel insights in two complex processes: reprogramming to
induced pluripotent stem cells (iPSCs) and hematopoiesis. In reprogramming,
chromatin changes could occur without large gene expression changes, different
combinations of activating marks were associated with specific reprogramming
factors, there was an order of acquisition of chromatin marks at pluripotency
loci, and multivalent states (comprising previously undetermined combinations of
activating and repressive histone modifications) were enriched for CTCF. In the
hematopoietic system, we defined critical decision points in the lineage tree,
identified regulatory elements that were enriched in cell-type-specific regions,
and found that the underlying chromatin state was achieved by specific erasure of
preexisting chromatin marks in the precursor cell or by de novo assembly. Our
method provides a systematic approach to model the dynamics of chromatin state to
provide novel insights into the relationships among cell types in diverse cell
fate specification processes.
PMID- 28424353
TI - Constrained release of lamina-associated enhancers and genes from the nuclear
envelope during T-cell activation facilitates their association in chromosome
compartments.
AB - The 3D organization of the genome changes concomitantly with expression changes
during hematopoiesis and immune activation. Studies have focused either on lamina
associated domains (LADs) or on topologically associated domains (TADs), defined
by preferential local chromatin interactions, and chromosome compartments,
defined as higher-order interactions between TADs sharing functionally similar
states. However, few studies have investigated how these affect one another. To
address this, we mapped LADs using Lamin B1-DamID during Jurkat T-cell
activation, finding significant genome reorganization at the nuclear periphery
dominated by release of loci frequently important for T-cell function. To assess
how these changes at the nuclear periphery influence wider genome organization,
our DamID data sets were contrasted with TADs and compartments. Features of
specific repositioning events were then tested by fluorescence in situ
hybridization during T-cell activation. First, considerable overlap between TADs
and LADs was observed with the TAD repositioning as a unit. Second, A1 and A2
subcompartments are segregated in 3D space through differences in proximity to
LADs along chromosomes. Third, genes and a putative enhancer in LADs that were
released from the periphery during T-cell activation became preferentially
associated with A2 subcompartments and were constrained to the relative proximity
of the lamina. Thus, lamina associations influence internal nuclear organization,
and changes in LADs during T-cell activation may provide an important additional
mode of gene regulation.
PMID- 28424356
TI - The direct and indirect influence of own mother's milk on bronchopulmonary
dysplasia and costs.
PMID- 28424354
TI - Less effective selection leads to larger genomes.
AB - The evolutionary origin of the striking genome size variations found in
eukaryotes remains enigmatic. The effective size of populations, by controlling
selection efficacy, is expected to be a key parameter underlying genome size
evolution. However, this hypothesis has proved difficult to investigate using
empirical data sets. Here, we tested this hypothesis using 22 de novo
transcriptomes and low-coverage genomes of asellid isopods, which represent 11
independent habitat shifts from surface water to resource-poor groundwater. We
show that these habitat shifts are associated with higher transcriptome-wide
[Formula: see text] After ruling out the role of positive selection and
pseudogenization, we show that these transcriptome-wide [Formula: see text]
increases are the consequence of a reduction in selection efficacy imposed by the
smaller effective population size of subterranean species. This reduction is
paralleled by an important increase in genome size (25% increase on average), an
increase also confirmed in subterranean decapods and mollusks. We also control
for an adaptive impact of genome size on life history traits but find no
correlation between body size, or growth rate, and genome size. We show instead
that the independent increases in genome size measured in subterranean isopods
are the direct consequence of increasing invasion rates by repeat elements, which
are less efficiently purged out by purifying selection. Contrary to selection
efficacy, polymorphism is not correlated to genome size. We propose that recent
demographic fluctuations and the difficulty of observing polymorphism variation
in polymorphism-poor species can obfuscate the link between effective population
size and genome size when polymorphism data are used alone.
PMID- 28424357
TI - Thin-for-gestational age infants are at increased risk of neurodevelopmental
delay at 2 years.
AB - BACKGROUND: Infants born small-for-gestational age (SGA) are at increased risk of
developmental difficulties. Identifying those most at risk is challenging. We
examined the effect of neonatal body composition and customised birthweight
centiles on neurocognitive and behavioural outcomes at age 2. STUDY DESIGN:
Prospective cohort study of term infants from the Cork BASELINE Birth Cohort
Study classified into the following exposure groups: a birth weight <10th
customised centile (SGA, n=51); body fat percentage at birth <10th centile (thin
for-gestational age (TGA, n=51)) or both SGA and TGA infants (small- and thin-for
gestational age (STGA), n=13). The SGA, TGA and STGA groups were compared with a
reference (unexposed) group of appropriate-for-gestational age (AGA, n=189)
infants. Outcome was assessed at 24 months using the Bayley Scales of Infant
Development Version III and the Child Behaviour Checklist. RESULTS: Outcomes in
the SGA infants did not differ significantly from the AGA group. TGA infants had
significantly lower scores across all three domains, with a 0.35, 0.38 and 0.41
SD reduction in language, cognitive and motor scale scores, respectively. STGA
infants had poorer cognitive outcome with a median cognitive scale score of 90
(IQR 85-95) compared with 95 (IQR 90-100) in the AGA reference group, p=0.005.
The adjusted OR of developmental delay at 2 years was 5.00 (95% CI 1.46 to 17.13,
p=0.010) in the STGA group. CONCLUSION: TGA infants, in particular those born
STGA, are at increased risk of developmental delay at 2 years compared with the
AGA infants.
PMID- 28424358
TI - Ultrasound assessment of umbilical venous catheter migration in preterm infants:
a prospective study.
AB - OBJECTIVES: To evaluate the umbilical venous catheter (UVC) tip position by
ultrasound and compare it with standard radiograph findings and to examine the
catheter tip migration rates during the first week of life. DESIGN: Prospective
observational study of inborn preterm infants who had an UVC placed and its
position radiographically confirmed. The first ultrasound was done on UVC
placement at median (IQR) age of 2 hours (1-4) and follow-up scans at a median
(IQR) age of 34 hours (27-44 hours), 77 hours (70-94 hours) and 6 days (5-7 days)
after insertion. Catheter tip was considered in optimum position if tip was lying
in the inferior vena cava up to the right atrium opening. RESULTS: We studied 65
infants at a mean (+/-SD) gestational age and birth weight of 26.4 (+/-2.1) weeks
and 808 (+/-289) g, respectively. Ultrasound confirmed optimum position of UVC
tip in 25/65 (38.5%) infants. Majority (38/40) of the malpositioned catheters
were located inside the heart with 15 reaching the left atrium. Catheter tip
migration occurred in 29 of 58 infants (50%) at any time during the first week.
The proportions of UVC migration were found to be 17%, 31% and 29% on subsequent
ultrasound with a trend to outward movement over time. CONCLUSION: UVC tip
localisation by standard radiography is very imprecise, and catheter tip
migration occurs in a significant proportion of infants during first weeks of
age. We suggest ultrasound as the best modality to assist localisation and follow
up of UVC tip in preterm infants.
PMID- 28424359
TI - Effects of combined tiotropium/olodaterol on inspiratory capacity and exercise
endurance in COPD.
AB - Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and
2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and
exercise endurance time in patients with moderate to severe chronic obstructive
pulmonary disease.For each patient, four of five treatments were administered
once daily for 6 weeks, with a 21-day washout between treatments:
tiotropium/olodaterol 2.5/5 ug or 5/5 ug, tiotropium 5 ug, olodaterol 5 ug or
placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity
prior to exercise and exercise endurance time during constant work-rate cycle
ergometry to symptom limitation at 75% of peak incremental work rate after 6
weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2,
respectively. Tiotropium/olodaterol 2.5/5 and 5/5 ug provided significant
improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001),
and significant improvements in exercise endurance time versus placebo
(p<0.0001). Intensity of breathing discomfort was reduced following both doses of
tiotropium/olodaterol versus placebo (p<0.0001).Once-daily tiotropium/olodaterol
yielded improvements in lung hyperinflation versus placebo and statistically
significant improvements versus monotherapies. Tiotropium/olodaterol also showed
improvements in dyspnoea and exercise tolerance versus placebo but not
consistently versus monotherapies.
PMID- 28424360
TI - Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance
through adipose tissue inflammation.
AB - Obstructive sleep apnoea (OSA) is increasingly associated with insulin
resistance. The underlying pathophysiology remains unclear but intermittent
hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose
tissue has been hypothesised to play a key role.We tested this hypothesis
employing a comprehensive translational approach using a murine IH model of lean
and diet-induced obese mice, an innovative IH system for cell cultures and a
tightly controlled patient cohort.IH led to the development of insulin resistance
in mice, corrected for the degree of obesity, and reduced insulin-mediated
glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin
signalling pathway and downregulation of insulin-receptor substrate-1 mRNA.
Providing mechanistic insight, IH induced a pro-inflammatory phenotype of
visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation
correlating with the severity of insulin resistance. Complimentary in vitro
analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages.
In subjects without comorbidities (n=186), OSA was independently associated with
insulin resistance. Furthermore, we found an independent correlation of OSA
severity with the M1 macrophage inflammatory marker sCD163.This study provides
evidence that IH induces a pro-inflammatory phenotype of the adipose tissue,
which may be a crucial link between OSA and the development of insulin
resistance.
PMID- 28424361
TI - Computed tomographic findings in subjects who died from respiratory disease in
the National Lung Screening Trial.
AB - We evaluated the prevalence of significant lung abnormalities on computed
tomography (CT) in patients who died from a respiratory illness other than lung
cancer in the National Lung Screening Trial (NLST).In this retrospective case
control study, NLST participants in the CT arm who died of respiratory illness
other than lung cancer were matched for age, sex, pack-years and smoking status
to a surviving control. A chest radiologist and a radiology resident blinded to
the outcome independently scored baseline CT scans visually and qualitatively for
the presence of emphysema, airway wall thickening and fibrotic lung disease. The
prevalence of CT abnormalities was compared between cases and controls by using
chi-squared tests.In total, 167 participants died from a respiratory cause other
than lung cancer. The prevalence of severe emphysema, airway wall thickening and
fibrotic lung disease were 28.7% versus 4.8%, 26.9% versus 13.2% and 18.6% versus
0.5% in cases and controls, respectively. Radiological findings were
significantly more prevalent in deaths compared with controls (all p<0.001).CT
diagnosed severe emphysema, airway wall thickening and fibrosis were much more
common in NLST participants who died from respiratory disease, and CT may provide
an additional means of identifying these diseases.
PMID- 28424362
TI - Effect of the cooling sensation induced by olfactory stimulation by L-menthol on
dyspnoea: a pilot study.
PMID- 28424363
TI - Yield of tuberculosis screening in asylum-seekers by country of origin: analysis
of screening data in a German federal state (2002-2015).
PMID- 28424364
TI - Time to take CT screening to the next level?
PMID- 28424365
TI - Language discordance between tuberculosis patients and healthcare providers
challenging universal access.
PMID- 28424366
TI - Sleep apnoea, insulin resistance and diabetes: the first step is in the fat.
PMID- 28424367
TI - Chronic obstructive pulmonary disease: inhale deeply and start to exercise.
PMID- 28424368
TI - Spatial intensity distribution analysis quantifies the extent and regulation of
homodimerization of the secretin receptor.
AB - Previous studies have indicated that the G-protein-coupled secretin receptor is
present as a homodimer, organized through symmetrical contacts in transmembrane
domain IV, and that receptor dimerization is critical for high-potency signalling
by secretin. However, whether all of the receptor exists in the dimeric form or
if this is regulated is unclear. We used measures of quantal brightness of the
secretin receptor tagged with monomeric enhanced green fluorescent protein
(mEGFP) and spatial intensity distribution analysis to assess this. Calibration
using cells expressing plasma membrane-anchored forms of mEGFP initially allowed
us to demonstrate that the epidermal growth factor receptor is predominantly
monomeric in the absence of ligand and while wild-type receptor was rapidly
converted into a dimeric form by ligand, a mutated form of this receptor remained
monomeric. Equivalent studies showed that, at moderate expression levels, the
secretin receptor exists as a mixture of monomeric and dimeric forms, with little
evidence of higher-order complexity. However, sodium butyrate-induced up
regulation of the receptor resulted in a shift from monomeric towards oligomeric
organization. In contrast, a form of the secretin receptor containing a pair of
mutations on the lipid-facing side of transmembrane domain IV was almost entirely
monomeric. Down-regulation of the secretin receptor-interacting G-protein Galphas
did not alter receptor organization, indicating that dimerization is defined
specifically by direct protein-protein interactions between copies of the
receptor polypeptide, while short-term treatment with secretin had no effect on
organization of the wild-type receptor but increased the dimeric proportion of
the mutated receptor variant.
PMID- 28424369
TI - Dietary capsaicin and its anti-obesity potency: from mechanism to clinical
implications.
AB - Obesity is a growing public health problem, which has now been considered as a
pandemic non-communicable disease. However, the efficacy of several approaches
for weight loss is limited and variable. Thus, alternative anti-obesity
treatments are urgently warranted, which should be effective, safe, and widely
available. Active compounds isolated from herbs are similar with the practice of
Traditional Chinese Medicine, which has a holistic approach that can target to
several organs and tissues in the whole body. Capsaicin, a major active compound
from chili peppers, has been clearly demonstrated for its numerous beneficial
roles in health. In this review, we will focus on the less highlighted aspect, in
particular how dietary chili peppers and capsaicin consumption reduce body weight
and its potential mechanisms of its anti-obesity effects. With the widespread
pandemic of overweight and obesity, the development of more strategies for the
treatment of obesity is urgent. Therefore, a better understanding of the role and
mechanism of dietary capsaicin consumption and metabolic health can provide
critical implications for the early prevention and treatment of obesity.
PMID- 28424370
TI - Multi-site binding of epigallocatechin gallate to human serum albumin measured by
NMR and isothermal titration calorimetry.
AB - The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was
measured in physiological conditions using NMR and isothermal titration
calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as
50 mM. NMR showed two binding events: strong (n1=1.8 +/- 0.2; Kd1 =19 +/- 12 MUM)
and weak (n2~20; Kd2 =40 +/- 20 mM). ITC also showed two binding events: strong
(n1=2.5 +/- 0.03; Kd1 =21.6 +/- 4.0 MUM) and weak (n2=9 +/- 1; Kd2 =22 +/- 4 mM).
The two techniques are consistent, with an unexpectedly high number of bound
EGCG. The strong binding is consistent with binding in the two Sudlow pockets.
These results imply that almost all EGCG is transported in the blood bound to
albumin and explains the wide tissue distribution and chemical stability of EGCG
in vivo.
PMID- 28424371
TI - Comprehensive assessment of cavernosography with 320-row dynamic volume CT versus
conventional cavernosography in erectile dysfunction patients caused by venous
leakage.
AB - The present study aims to investigate and compare the diagnostic and prognostic
value of cavernosography with 320-row dynamic volume computed tomography (DVCT)
versus conventional cavernosography in men with erectile dysfunction (ED) caused
by venous leakage. A total of 174 patients diagnosed with ED were enrolled and
received cavernosography with 320-row DVCT (DVCT group) and conventional
cavernosography scans (control group) respectively. The diagnosis, complications,
and prognosis of patients were evaluated. The DVCT group provided high-resolution
images with less processing and testing time, as well as lowered radiological
agent and contrast agent compared with the control group. In the DVCT group, 89
patients who were diagnosed with venous ED had six various venous leakage, namely
superficial venous leakage, profundus venous leakage, the mixed type, cavernosal
venous leakage, crural venous leakage, and also venous leakage between the penis
and urethra cavernosum (9, 21, 32, 6, 18, and 3 cases respectively). Similarly,
74 patients out of the 81 who suffered from venous ED were classified to have
superficial venous leakage (11), profundus venous leakage (14), the mixed type
venous leakage (26), and middle venous leakage (23). Six out of 25 patients in
the DVCT group, had improvements in ED while the remaining 19 achieved full
erectile function recovery with no penile fibrosis and erectile pain.
Cavernosography with 320-row DVCT is a reliable system that can be used to
diagnose ED caused by venous leakage. This is especially useful in accurately
determining the type of venous and allows for a better prognosis and direction of
treatment.
PMID- 28424372
TI - Effects of drought stress on global gene expression profile in leaf and root
samples of Dongxiang wild rice (Oryza rufipogon).
AB - Drought is a serious constraint to rice production throughout the world, and
although Dongxiang wild rice (Oryza rufipogon, DXWR) possesses a high degree of
drought resistance, the underlying mechanisms of this trait remains unclear. In
the present study, cDNA libraries were constructed from the leaf and root tissues
of drought-stressed and untreated DXWR seedlings, and transcriptome sequencing
was performed with the goal of elucidating the molecular mechanisms involved in
drought-stress response. The results indicated that 11231 transcripts were
differentially expressed in the leaves (4040 up-regulated and 7191 down
regulated) and 7025 transcripts were differentially expressed in the roots (3097
up-regulated and 3928 down-regulated). Among these differentially expressed genes
(DEGs), the detection of many transcriptional factors and functional genes
demonstrated that multiple regulatory pathways were involved in drought
resistance. Meanwhile, the DEGs were also annotated with gene ontology (GO) terms
and key pathways via functional classification and Kyoto Encyclopedia of Gene and
Genomes (KEGG) pathway mapping, respectively. A set of the most interesting
candidate genes was then identified by combining the DEGs with previously
identified drought-resistant quantitative trait loci (QTL). The present work
provides abundant genomic information for functional dissection of the drought
resistance of DXWR, and findings will further help the current understanding of
the biological regulatory mechanisms of drought resistance in plants and
facilitate the breeding of new drought-resistant rice cultivars.
PMID- 28424373
TI - Statins, PCSK9 inhibitors and cholesterol homeostasis: a view from within the
hepatocyte.
AB - Statins and PCSK9 inhibitors dramatically lower plasma LDL levels and
dramatically increase LDL receptor number within hepatocyte cell membranes. It
seems self-evident that total clearance of LDL particles from plasma and total
delivery of cholesterol to the liver must increase in consequence. However, based
on the results of stable isotope tracer studies, this analysis demonstrates the
contrary to be the case. Statins do not change the production rate of LDL
particles. Accordingly, at steady state, the clearance rate cannot change.
Because LDL particles contain less cholesterol on statin therapy, the delivery of
cholesterol to the liver must, therefore, be reduced. PCSK9 inhibitors reduce the
production of LDL particles and this further reduces cholesterol delivery to the
liver. With both agents, a larger fraction of a smaller pool is removed per unit
time. These findings are inconsistent with the conventional model of cholesterol
homeostasis within the liver, but are consistent with a new model of regulation,
the multi-channel model, which postulates that different lipoprotein particles
enter the hepatocyte by different routes and have different metabolic fates
within the hepatocyte. The multi-channel model, but not the conventional model,
may explain how statins and PCSK9 inhibitors can produce sustained increases in
LDL receptor number.
PMID- 28424374
TI - Mechanisms of vascular disease in dementia: what does industry want to know?
AB - Despite recent advances in basic and clinical science, dementia remains an area
of high unmet medical need. The role of cerebrovascular mechanisms in the
pathogenesis and progression of cognitive and functional impairment in dementia
is being revived. In order to facilitate the development of therapeutic
approaches, it is critical that a number of fundamental elements are integrated
into research strategies investigating cerebrovascular pathologies as these will
maximize the opportunity of bringing medicines to patients in a timely manner.
PMID- 28424375
TI - Mitochondria: a central target for sex differences in pathologies.
AB - It is increasingly acknowledged that a sex and gender specificity affects the
occurrence, development, and consequence of a plethora of pathologies.
Mitochondria are considered as the powerhouse of the cell because they produce
the majority of energy-rich phosphate bonds in the form of adenosine tri
phosphate (ATP) but they also participate in many other functions like steroid
hormone synthesis, reactive oxygen species (ROS) production, ionic regulation,
and cell death. Adequate cellular energy supply and survival depend on
mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics,
and quality control via mitophagy. It appears that mitochondria are the place of
marked sexual dimorphism involving mainly oxidative capacities, calcium handling,
and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial
function and biogenesis. Mutations in genes encoding mitochondrial proteins are
the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction
is also an important parameter for a large panel of pathologies including
neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs),
metabolic disorders, neuropathies, renal dysfunction etc. Many of these
pathologies present sex/gender specificity. Here we review the sexual dimorphism
of mitochondria from different tissues and how this dimorphism takes part in the
sex specificity of important pathologies mainly CVDs and neurological disorders.
PMID- 28424377
TI - Sex differences in micro- and macro-vascular complications of diabetes mellitus.
AB - Vascular complications are a leading cause of morbidity and mortality in both men
and women with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus, however the
prevalence, progression and pathophysiology of both microvascular (nephropathy,
neuropathy and retinopathy) and macrovascular [coronary heart disease (CHD),
myocardial infarction, peripheral arterial disease (PAD) and stroke] disease are
different in the two sexes. In general, men appear to be at a higher risk for
diabetic microvascular complications, while the consequences of macrovascular
complications may be greater in women. Interestingly, in the absence of diabetes,
women have a far lower risk of either micro- or macro-vascular disease compared
with men for much of their lifespan. Thus, the presence of diabetes confers
greater risk for vascular complications in women compared with men and some of
the potential reasons, including contribution of sex hormones and sex-specific
risk factors are discussed in this review. There is a growing body of evidence
that sex hormones play an important role in the regulation of cardiovascular
function. While estrogens are generally considered to be cardioprotective and
androgens detrimental to cardiovascular health, recent findings challenge these
assumptions and demonstrate diversity and complexity of sex hormone action on
target tissues, especially in the setting of diabetes. While some progress has
been made toward understanding the underlying mechanisms of sex differences in
the pathophysiology of diabetic vascular complications, many questions and
controversies remain. Future research leading to understanding of these
mechanisms may contribute to personalized- and sex-specific treatment for
diabetic micro- and macro-vascular disease.
PMID- 28424376
TI - SerpinC1/Antithrombin III in kidney-related diseases.
AB - The gene SerpinC1 encodes a serine protease inhibitor named antithrombin III
(ATIII). This protease demonstrates both anticoagulant and anti-inflammatory
action. ATIII is the most important coagulation factor inhibitor, and even minor
changes in ATIII can significantly alter the risk of thromboembolism. ATIII can
also suppress inflammation via a coagulation-dependent or -independent effect.
Moreover, apart from ATIII deficiency, ATIII and its gene SerpinC1 may also be
related to many diseases (e.g. hypertension, kidney diseases). The present review
summarizes how ATIII affects the progress of kidney disease and its mechanism.
Further studies are required to investigate how ATIII affects renal function and
the treatment.
PMID- 28424378
TI - [Recognition, care and prevention of suicidal behaviour in adults].
AB - : Suicide is a major public health problem everywhere in the world and in the WHO
European Region suicide accounts for over 120,000 deaths per year. 1. Recognition
and diagnosis: An underlying psychiatric disorder is present in up to 90% of
people who completed suicide. Comorbidity with depression, anxiety, substance
abuse and personality disorders is high. In order to achieve successful
prevention of suicidality, adequate diagnostic procedures and appropriate
treatment for the underlying disorder are essential. 2. Treatment and care: Acute
intervention should start immediately in order to keep the patient alive.
Existing evidence supports the efficacy of pharmacological treatment and
cognitive behavioural therapy (including dialectical behavior therapy and problem
solving therapy) in preventing suicidal behaviour. Some other psychological
treatments are promising, but the supporting evidence is currently insufficient.
Studies show that antidepressant and mood stabilizer treatments decrease the risk
for suicidality among responders in mood disorder patients. However, the risk of
suicidal behaviour in depressed patients treated with antidepressants exists
during the first 10-14 days of treatment, which requires careful monitoring.
Short-term supplementary medication with anxiolytics and hypnotics in the case of
anxiety and insomnia is recommended. Treatment with antidepressants of children
and adolescents should only be given under supervision of a specialist. Long-term
treatment with lithium has been shown to be very effective in preventing both
suicide and attempted suicide in patients with unipolar and bipolar depression.
Treatment with clozapine is effective in reducing suicidal behaviour in patients
with schizophrenia. Other atypical antipsychotics are promising but more evidence
is required. 3. Family and social support: The suicidal person should always be
motivated to involve family in the treatment. Psychosocial treatment and support
is recommended, as the majority of suicidal patients have problems with
relationships, work, school and lack functioning social networks. 4. SAFETY: A
secure home, public and hospital environment, without access to suicidal means is
a necessary strategy in suicide prevention. Each treatment option, prescription
of medication and discharge of the patient from hospital should be carefully
evaluated against the involved risks. 5. Education of treatment team: Training of
general practitioners is effective in the prevention of suicide. It improves
treatment of depression and anxiety, quality of the provided care and attitudes
towards suicide. Continuous training including discussions about ethical and
legal issues is necessary for psychiatrists and other mental health
professionals. Multidisciplinary treatment teams including psychiatrist and other
professionals such as psychologist, social worker, and occupational therapist are
always preferable, as integration of pharmacological, psychological and social
rehabilitation is recommended especially for patients with chronic suicidality.
6. Public aspects: Not only the health care workers are responsible for suicide
prevention. All members of our society (including community/political leaders as
well as religious and civil organizations) have their own task with more or less
competence and responsibility.
PMID- 28424379
TI - [Risk factors of eating disorders in the narratives of fashion models].
AB - INTRODUCTION: The risk of eating disorders is high in populations who are exposed
to slimness ideal, so among fashion models. The present qualitative study
evaluates the risk factors of eating disorders in a group of fashion models with
semistructured interview. Moreover, the aim of the study was to examine the
impact of professional requirements on the health of models. METHODS: The study
group was internationally heterogeneous. The models were involved by personal
professional relationship. A semistructured questionnaire was used by e-mail
containing anthropometric data and different aspects of the model profession.
RESULTS: 29 female and three male models, three agents, two designers, three
fotographers, one personal trainer and one stylist answered the questionnaire.
Transient bulimic symptoms were reported by six female models (21%). Moreover,
five female models fulfilled the DSM-5 criteria of anorexia nervosa or bulimia
nervosa. Four of them were anorexic (body mass index: 13.9-15.3), one was
bulimic. The symptoms of three persons began before the model career, those of
two models after it. 17 models reported that the model profession intensively
increased the bodily preoccupations. CONCLUSION: The study corroborates the
effect of the model profession on the increase of the risk for eating disorders.
In the case of the models, whose eating disorder began after stepping into the
model profession, the role of the representants of the fashion industry can be
suggested as a form of psychological abuse. As the models or in the case of
underages their parents accepted the strong requirement of slimness, an
unconscious collusion is probable. Our date highlight the health impact of
cultural ideals, and call the attention to prevention strategies.
PMID- 28424380
TI - [Schizotypy: detachment or magical fusion].
AB - Nowadays, both in the clinical population, and in general communities, we tend to
encounter an increasing number of personality disorder patients, whose social
adjustment, partnerships and efficient life management is made difficult by the
disorder. The ideas of borderline personality disorder patients, who fluctuate
between farfetched expectations and fears of their selves being demolished,
schizoid patients, who close their selves in their own alienating prison,
avoidant patients, who try to escape difficulties, which would enhance their self
esteem, OCD patients, who build their own mythic superstitious world, and
antisocial patients who tend to ignore and aggressively override others'
interests are all important in the development of cultures with insecure
identities. Taking into consideration the symptoms enlisted in the diagnostic
system of DSM-5, it is the task of experts of cultural anthropology, psychology,
psychopathology and cognitive neuroscience to explore the referring ways of
personality development, relationships and of conflict management.
Notwithstanding, avoiding the psychopathological terminology, rather pointing at
population characteristics, we need to identify personal functionings of the
general features of perception, cognition and world views, which in the long run,
may modify personal developmental possibilities, individual approaches to
information technology, and emotional, family or professional motivations. Based
on the respective literature and clinical experience, below we intend to explore
the different aspects of schizotypy, which contribute to the formation of
schizoid personality disorder. We analyze the interrelations of avoiding
relationships and empathy toward relationship building.
PMID- 28424381
TI - [The relationship between physical activity and executive functions among
children with attention-deficit hyperactivity disorder].
AB - The connection between physical activity and executive functions has recently
started to emerge as a new focus of research within the field of attention
deficit-hyperactivity-disorder (ADHD). In the present paper we summarise the
major findings of these studies concentrating specifically on paediatric
population. We present the results of six studies that focus on the connection
between acute physical activity and executive functions and seven others that
examine the relationship between chronic physical activity and executive
functions in children with ADHD. The forms of physical activity as well as the
executive functions measured show great variability within the studies reviewed.
Four out of the six studies using acute physical activity, and all of the studies
using chronic physical activity have found evidence of improvement in at least
some areas of executive functioning. Further studies are needed to confirm the
applicability of acute as well as chronic physical activity as a potential
additional treatment in ADHD. Also, clarifying the optimal parameters (i.e. type,
intensity, duration, frequency) of physical activity while also taking into
consideration the individual characteristics (i.e. gender, age, physical
fittness, type of ADHD, comorbidity) of children with ADHD could be important
aims of future studies.
PMID- 28424382
TI - [Near miss outcomes in gambling games].
AB - BACKGROUND: Games of chance operate with an intermittent reinforcement schedule
in which the number of games takes the player to win differ in each turn thus
they can not predict when the next positive reinforcement arrives. The near miss
outcome (close to winning but actually a losing outcome) can be interpreted as a
secondary (built in) reinforcement within variable ratio reinforcement schedule
that presumably contribute to the development and maintanance of gambling
addiction. METHODS: The aim of this publication would be to introduce near miss
outcomes and to summarize and critically analyze literature connected to this
issue.We searched internet datebases using word "near miss" and analyse articles
focusing on gambling games. RESULTS: Based on numerous authors' results a near
miss rate set at around 30% increases the desire to continue playing among
gamblers and players who have no former gambling experience as well. CONCLUSIONS:
Some studies have demonstrated that this effect might be related to the extent
the player has the situation under control during the gambling session. The
hypothetical inhibiting effect of a 45% near miss ratio has not yet been proven.
Neurobiological researches show middle-cerebral activity during near miss
outcomes furthermore similar physiological patterns have been discovered
following a near miss and winning outcomes. Regarding the connection between
intrapsychic variables (cognitive and personality factors) and near misses there
are very few studies. The fact that different authors interpret near miss
outcomes differently even when studying the same game leads to problems in
interpreting their results. It follows from the foregoing empirical results that
near miss outcomes contribute to the development and maintanance of pathological
gambling but we have little information on the factors implementing this effect.
PMID- 28424383
TI - [Long-acting injection - four-times-a-year. Review of the 3-monthly paliperidone
palmitate injection].
AB - Continuous maintenance antipsychotic treatment is one of the most important
factor in the long-term course of schizophrenia. Among the therapeutic options
available today, the long-acting injectable antipsychotics are those that are
able to efficiently provide an optimal treatment strategy required for continuous
maintenance treatment. Three-monthly paliperidone palmitate (TREVICTA) is an
important milestone in this therapeutic approach, since it is the first and only
antipsychotic treatment for patients with schizophrenia, which provides the
yearly maintenance therapeutic dose by four injections. Clinical studies have
shown that compared to the placebo, TREVICTA significantly delays time to
relapse, reduces relapse rate, and its effect is equivalent to the well-known
monthly paliperidone palmitate. Data on safety have revealed that TREVICTA was
well tolerated and safe, and the rare side effects were consistent with that of
paliperidone previously described. In conclusion, TREVICTA is a new and unique
treatment option for patients who respond well to paliperidone treatment.
PMID- 28424384
TI - Minor physical anomalies and dermatoglyphic signs in affective disorders: A
systematic review.
AB - The increased prevalence of minor physical anomalies (MPAs) and the abnormalities
of dermatoglyphic patterns may be physical manifestations of neurodevelopmental
disruption in affective disorders. This paper aims to review the current state of
knowledge on the frequency of MPAs and dermatoglyphic abnormalities in mood
disorders. A MEDLINE, PsychInfo and Web of Science search was carried out to
collect all publications on the frequency of MPAs and on dermatoglyphic traits in
bipolar disorder and unipolar depression. 24 studies on MPAs, 19 on
dermatoglyphics, and 5 dealing with both were found with discrepant findings. The
relative contribution of neurodevelopmental retardation to the aetiology of
affective disorders remains undetermined, the field is open for further research.
Increased recognition of neurodevelopmental processes in the origin of affective
disorders may allow for earlier and more effective intervention and prevention.
PMID- 28424385
TI - [Korbinian Brodmann's Scientific Profile, and Academic Works].
AB - Brodmann's map is one of the best known maps of the human cerebral cortex.
However, Korbinian Brodmann's 1909 monograph, containing the first map, has not
been widely read by neurologists. Following the publication of the first map,
Brodmann reproduced the map in 1910, and again in 1914, with several important
differences. The latter map is also characterized by the exclusion of Brodmann
area numbers, "12-16, and 48-51;" contrastingry numbers "1-52" have been
described in the animal brain. Here, we provide a detailed explanation of the
versions of Brodmann's maps, and review his academic profile and works.
PMID- 28424386
TI - [Touch: Brodmann Areas 3, 1, and 2].
AB - A brief history of cytoarchitectonic studies of Brodmann areas 3, 1, and 2 is
presented here. Results of neurophysiological studies, i.e., recordings of single
neuronal activities in these three cytoarchitectonic areas of the monkey brain
are described and interpreted on the basis of a hierarchial schema model of
information processing. Finally, recent studies on the human postcentral gyrus
are reviewed and compared with the results of the aforementioned monkey studies.
PMID- 28424387
TI - [Cortical Areas for Controlling Voluntary Movements].
AB - The primary motor cortex is located in Brodmann area 4 at the most posterior part
of the frontal lobe. The primary motor cortex corresponds to an output stage of
motor signals, sending motor commands to the brain stem and spinal cord. Brodmann
area 6 is rostral to Brodmann area 4, where multiple higher-order motor areas are
located. The premotor area, which is located in the lateral part, is involved in
planning and executing action based on sensory signals. The premotor area
contributes to the reaching for and grasping of an object to achieve a behavioral
goal. The supplementary motor area, which occupies the mesial aspect, is involved
in planning and executing actions based on internalized or memorized signals. The
supplementary motor area plays a central role in bimanual movements, organizing
multiple movements, and switching from a routine to a controlled behavior. Thus,
Brodmann areas 4 and 6 are considered as central motor areas in the cerebral
cortex, in which the idea of an action is transformed to an actual movement in a
variety of contexts.
PMID- 28424388
TI - [Interface Between Brain and Outside].
AB - Areas 5 and 7 are the association cortices which are located in the parietal lobe
and process somatosensory and visual information, respectively. The location of
area 7 differ in the Brodmann's human and monkey brain map, in the human brain
map area 7 is located in the superior parietal lobe, while it is in the inferior
parietal lobe in the monkey brain map. Thus, it is difficult to discuss the
function of these areas.
PMID- 28424389
TI - [Brodmann Areas 8 and 9 Including the Frontal Eye Field].
AB - Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain
areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys.
Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey
PFCs, and proposed slightly different brain maps for both species. They assigned
numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9.
Areas 8 and 9 have both lateral and medial regions respectively. The lateral area
8 is important for conditional discrimination learning. The frontal eye field
which occupies the most caudal region of area 8, is responsible for visual
attention and control of eye movements. The lateral area 9 and area 9/46 are
functionally similar to area 46 and play important roles in executive control.
The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8
and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also
known to show "default mode of brain activity" (i.e., more activity during rest
than during cognitive task).
PMID- 28424390
TI - [Area 10, 38: Prospective Functions in BA10 and Semantic Hub in BA38].
AB - This paper reviews the structural specificities and functional roles in Brodmann
areas 10 and 38. A number of studies have focused on both areas through various
approaches including neuropsychology, neuroimaging, psychiatry, neurology, and
neurosurgery. Both areas 10 and 38 may have a substantially very complex higher
order cognitive functions, which are quite hard to disentangle. Here, I picked up
some fundamental perspectives for reviewing previous studies, to provide
efficient research orientations for the elucidation of functions in both areas.
PMID- 28424391
TI - [Brodmann Areas 11, 46, and 47: Emotion, Memory, and Empathy].
AB - Brodmann area 11 is one of the main constituent of the orbitofrontal cortex, and
area 46 is that of the dorsolateral prefrontal cortex. The main function of
Brodmann area 11 is the processing of emotion and value, whereas the main
function of Brodmann area 46 is the processing of cognitive information,
including working memory. In comparison, the function of area 47 is more complex.
This area is related to the feeling of empathy towards the story contents of
others, which is thought to be the emotional aspect of this area, while this area
is also activated during automated action. This is in contrast with the function
of area 46, which is involved in willed action. In addition, area 47 in the left
hemisphere plays an important role in syntax processing.
PMID- 28424392
TI - [The Role of Brodmann Area 12: Taste, Social Cognition, and Mental Time].
AB - Broadman area 12, together with area 11, is located in the orbitofrontal area. A
voxel-based morphometric (VBM) study revealed the association between bilateral
brodmann areas 12/47 and taste disturbance in individuals with frontotemporal
lobar degeneration (FTLD). In our VBM study in patients with Parkinson's disease,
decision-making impairments were associated with atrophy of the bilateral
Brodmann area 12, indicating that this area may play an important role in social
cognitive function. Our recent study also demonstrated that this area may serve
as time order judgement or mental time travel.
PMID- 28424393
TI - [Regulation of Behavior Based on Interoception].
AB - It is well known that the insular cortex (Brodmann areas 13, 14, 15, and 16)
located deep inside the Sylvian fissure is associated with mental functions such
as perception, language, cognition, affect, and movement. In particular, the
insular cortex has been linked to interoception, which is the representation of
bodily physiological states that is used to regulate bodily states and mental
functions. Recently, a common principle to explain such functions of the insular
cortex has been proposed. The principle posits that the anterior insula generates
predictions of future bodily states, computes the error by comparing the
prediction with the actual sensory signals, and integrates the body with the mind
by minimizing the prediction error. This article describes the functions of the
insular cortex, and discusses the possibility that an error-minimizing function
can affect decision-making to regulate behaviors.
PMID- 28424394
TI - [Brodmann Areas 17, 18, and 19 in the Human Brain: An Overview].
AB - Brodmann areas 17, 18, and 19 in the human brain are visual cortices of the
occipital lobe. Each area has its own retinotopic representations, particulary
area 19, which has many small retinotopic areas representing half or all of the
contralateral visual field, several functional areas, and nine cytoarchitectonic
areas. Several fasciculi are known as occipital fiber connections, but their
precise endpoints are not clear. Lesions in the visual cortices cause several
visual disorders including visual field defect, visual hallucinations,
metamorphopsia, and different kinds of visual agnosia.
PMID- 28424395
TI - [Brodmann Areas 20, 21, and 22 in the Cerebral Cortex].
AB - The 20, 21, and 22 areas in the temporal lobe as classified by Brodmann are
almost identical with Economo and Koskinas's TA, TE1, and TE2, and, generally,
with the gyrus, middle temporal gyrus, and inferior temporal gyrus according to
brain anatomy. Before Brodmann's classification, Flechsig published his book
"Soul and Brain" in 1897, in which primary, secondary, and association areas in
the brain were classified. More recently, results from research using magnetic
resonance imaging (MRI) and fMRI support the parcellation of the cerebral cortex
proposed by Flechsig, Brodmann, and Economo more than one century ago.
PMID- 28424396
TI - [The Center of Sadness, Pain, and Recognition].
AB - The posterior cingulate cortex (Brodmann area, BA 23) is the hub of the default
mode network (DMN). Moreover, its network connectivity decreases early in
Alzheimer disease. The anterior cingulate cortex (BA 24) is connected to networks
such as the DMN, working memory network (WMN), and salience network (SN) and
plays a role in network coordination. The subgenual anterior cingulate cortex
(sgACC) on the rostral region of the anterior cingulated cortex is suggested to
be associated with depression.
PMID- 28424397
TI - [Spatial Cognition and Episodic Memory Formation in the Limbic Cortex].
AB - The limbic lobe defined by Broca is a cortical region with highly diverse
structure and functions, and comprises the paleo-, archi-, and neocortices as
well as their transitional zones. In the limbic lobe, Brodmann designated areas
27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29,
30, 31, 32, and 33 around the corpus callosum. In the current literature, areas
27 and 28 correspond to the presubiculum and entorhinal cortex, respectively.
Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35
and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25,
32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30,
and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior
portion of area 24 are deeply involved in emotional responses, particularly in
their autonomic functions, through reciprocal connections with the amygdaloid
complex, anterior thalamus and projections to the brainstem and spinal visceral
centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31,
the dorsolateral prefrontal areas, and the regions related to the hippocampus.
They play pivotal roles in mediating spatial cognition, working memory
processing, and episodic memory formation.
PMID- 28424398
TI - [Brodmann Areas 27, 28, 36 and 37: The Parahippocampal and the Fusiform Gyri].
AB - First, Brodmann areas 27, 28, 36 and 37, were anatomically defined in the
beginning of this review. These areas exist in the parahippocampal or fusiform
gyrus of the ventral temporal lobe in humans. Subsequently, the current
understanding of their functions was summarized on the basis of recent findings
mainly through human functional neuroimaging studies and animal studies. Rodent
studies have shown the existence of neuronal activities for representing space,
such as those involving head-direction cells or grid cells, in areas 27 (the
parasubicular cortex) and 28 (the ventral entorhinal cortex). Recent human
neuroimaging studies have provided support for the idea that grid cells may also
exist in the human entorhinal cortex. Many previous animal studies have shown
that area 36 (the lateral perirhinal cortex) is crucial for various types of
associative learning. Earlier human neuroimaging studies have also indicated that
faces, bodies and visual word forms are represented in different regions of area
37 in the posterior fusiform gyrus. Recent neuroimaging studies in humans have
shown substantial functional differentiation between face-related regions in
areas 37 and 36, which is similar to that seen in macaque monkeys, as shown
through their face patches. This implies the crucial involvement of both areas in
face processing.
PMID- 28424399
TI - [Recent Advancements in Understanding Hippocampal Functions].
AB - The hippocampal formation located in the medial temporal lobe of the brain has
been studied extensively for several decades, both in in vitro slice preparations
and in vivo living animals. Recent advancements in large-scale recording
techniques, such as multisite silicon probes and tetrodes, enable us to examine
the detailed characteristics of temporal spiking patterns of tens or hundreds of
neurons in the hippocampal circuit. Here, we introduce how such tools contribute
to our understanding of the hippocampal network dynamics and review several
hippocampal functions for information processing in the brain, including pattern
separation and completion, spatial representation, and encoding of positive and
negative valence.
PMID- 28424400
TI - [Brodmann Areas 39 and 40: Human Parietal Association Area and Higher Cortical
Function].
AB - The anatomy and function of the angular gyrus (Brodmann Area 39) and
supramarginal gyrus (Brodmann Area 40) are described here. Both gyri constitute
the inferior part of the parietal lobe. Association fibers from the angular gyrus
project to the dorsolateral prefrontal cortex via the superior longitudinal
fasciculus (SLF) II/arcuate fasciculus (AF), whereas those from the supramarginal
gyrus project to the ventrolateral prefrontal cortex via SLF III/AF. Damage to
the left angular gyrus causes kanji agraphia (lexical agraphia) and mild anomia,
whereas damage to the left supramarginal gyrus causes kana alexia (phonological
dyslexia) and kana agraphia (phonological agraphia). Damage to either gyrus
causes Gerstmann's syndrome (finger agnosia, left-right disorientation, agraphia
and acalculia) and verbal short-term memory impairment. "Angular alexia with
agraphia" results from damage to the middle occipital gyrus posterior to the
angular gyrus. Alexia and agraphia, with lesions in the angular or supramarginal
gyrus, are characterized by kana transposition errors in reading words, which
suggests the impairment of sequential phonological processing.
PMID- 28424401
TI - [The Map of Auditory Function].
AB - Brodmann areas 41 and 42 are located in the superior temporal gyrus and regarded
as auditory cortices. The fundamental function in audition is frequency analysis;
however, the findings on tonotopy maps of the human auditory cortex were not
unified until recently when they were compared to the findings on inputs and
outputs of the monkey auditory cortex. The auditory cortex shows plasticity after
conditioned learning and surgery of cochlear implant. It is also involved in
speech perception, music appreciation, and auditory hallucination in
schizophrenia through interactions with other brain areas, such as the thalamus,
frontal cortex, and limbic systems.
PMID- 28424402
TI - [Syntactic Processing in Broca's Area: Brodmann Areas 44 and 45].
AB - Brodmann areas 44 and 45 are known as Broca's area; however, their true
functional roles are still unknown. Recent developments in neuroimaging
techniques revealed the structures and functions of Broca's area in detail. More
specifically regarding language functions, sufficient evidence has been
accumulated that this region subserves the center of syntactic processing, not
necessarily motor functions. Here, we review a role of Broca's area as the
grammar center, including other roles in nonlinguistic functions.
PMID- 28424403
TI - [Non-Convulsive Status Epilepticus Caused by Hyponatremia in an Elderly Woman: A
Case Report].
AB - We report the case of a 67-year-old woman with non-convulsive status epilepticus
(NCSE) due to hyponatremia. She had a history of psychogenic polydipsia but not
epilepsy. She was admitted to our hospital with dysbulia. On admission, she was
confused and disoriented (Glasgow Coma Scale: 6, E1V1M4). Magnetic resonance
imaging of the brain showed no abnormalities. Laboratory test showed hyponatremia
(Na+ level: 115 mEq/L). The electroencephalography (EEG) showed a
generalized slow wave of 5 Hz during recording. The slow wave was promptly
suppressed by diazepam and levetiracetam administered intravenously and orally,
respectively. After the hyponatremia was treated the seizures stopped and did not
reoccur, even after cessation of the anticonvulsant drugs. The patient was
discharged with no neurological deficits. Few reports have described this
condition. Here we discuss the diagnosis and treatment of NCSE due to
hyponatremia. (Received May 31, 2016; Accepted December 12, 2016; Published April
1, 2017).
PMID- 28424404
TI - Upregulation of minichromosome maintenance complex component 3 during epithelial
to-mesenchymal transition in human prostate cancer.
AB - Metastasis is often associated with epithelial-to-mesenchymal transition (EMT).
To understand the molecular mechanisms of this process, we conducted proteomic
analysis of androgen-repressed cancer of the prostate (ARCaP), an experimental
model of metastatic human prostate cancer. The protein signatures of epithelial
(ARCaPE) and mesenchymal (ARCaPM) cells were consistent with their phenotypes.
Importantly, the expression of mini-chromosome maintenance 3 (MCM3) protein, a
crucial subunit of DNA helicase, was significantly higher in ARCaPM cells than
that of ARCaPE cells. This increased MCM3 protein expression level was verified
using Western blot analysis of the ARCaP cell lineages. Furthermore,
immunohistochemical analysis of MCM3 protein levels in human prostate tissue
specimens showed elevated expression in bone metastasis and advanced human
prostate cancer tissue samples. Subcutaneous injection experiments using ARCaPE
and ARCaPM cells in a mouse model also revealed increased MCM3 protein levels in
mesenchymal-derived tumors. This study identifies MCM3 as an upregulated molecule
in mesenchymal phenotype of human prostate cancer cells and advanced human
prostate cancer specimens, suggesting MCM3 may be a new potential drug target for
prostate cancer treatment.
PMID- 28424405
TI - The Bruton's tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects
through regulation of tumor-infiltrating macrophages.
AB - The Bruton's tyrosine kinase (Btk) inhibitor ibrutinib has demonstrated promising
efficacy in a variety of hematologic malignancies. However, the precise mechanism
of action of the drug remains to be fully elucidated. Tumor-infiltrating
macrophages presented in the tumor microenvironment have been shown to promote
development and progression of B-cell lymphomas through crosstalk mediated by
secreted cytokines and chemokines. Because Btk has been implicated in Toll-like
receptor (TLR) signaling pathways that regulate macrophage activation and
production of proinflammatory cytokines, we investigated the immunomodulatory
effects of Btk inhibitor on macrophages. Our results demonstrate that Btk
inhibition efficiently suppresses production of CXCL12, CXCL13, CCL19, and VEGF
by macrophages. Furthermore, attenuated secretion of homeostatic chemokines from
Btk inhibitor-treated macrophages significantly compromise adhesion, invasion,
and migration of lymphoid malignant cells and even those not driven by Btk
expression. The supernatants from Btk inhibitor-treated macrophages also impair
the ability of endothelial cells to undergo angiogenic tube formation.
Mechanistic analysis revealed that Btk inhibitors treatment downregulates
secretion of homeostatic chemokines and cytokines through inactivation of Btk
signaling and the downstream transcription factors, NF-kappaB, STAT3, and AP-1.
Taken together, these results suggest that the encouraging therapeutic efficacy
of Btk inhibitor may be due to both direct cytotoxic effects on malignant B cells
and immunomodulatory effects on macrophages present in the tumor
microenvironment. This novel mechanism of action suggests that, in addition to B
cell lymphomas, Btk inhibitor may also have therapeutic value in lymphatic
malignancies and solid tumors lacking Btk expression.
PMID- 28424406
TI - Targeting CCR2 with its antagonist suppresses viability, motility and invasion by
downregulating MMP-9 expression in non-small cell lung cancer cells.
AB - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which
is the leading cancer killer in the world. Despite the recent advances in its
diagnosis and therapy, the prognosis of NSCLC patients remains very poor, mainly
due to the development of drug resistance and metastasis. Both the chemokine
network and the matrix metalloproteinase (MMP) system play important roles in
cancer cell metastasis. The disruption of CCL2/CCR2 chemokine signaling has been
shown to suppress cancer cellviability and metastasis. CCL2-neutralizing
antibodies, which have shown promising therapeutic efficacy in several cancer
models, are not widely used due to technical issues. CCR2 antagonism has thus
become an alternative method for cancer treatment. However, the effect of CCR2
antagonists on NSCLC progression remains poorly understood. Here, we investigated
the effect of CCR2 antagonist (CAS445479-97-0) on the proliferation, migration
and invasion of human lung adenocarcinoma A549 cells by using WST-1 cell
viability assay, transwell migration assay, wound healing scratch assay and
Matrigel invasion assay. We demonstrated that CCL2 treatment promoted A549 cell
viability, motility and invasion by upregulating MMP-9 expression and that this
induction was significantly suppressed by CAS 445479-97-0. Taken together, our
data suggested that the CCR2 antagonist would be a potential drug for treating
CCR2-positive NSCLC patients.
PMID- 28424407
TI - The expression of histone deacetylase HDAC1 correlates with the progression and
prognosis of gastrointestinal malignancy.
AB - Gastrointestinal malignancy is a severe public health threat worldwide, and
survival for most types of gastrointestinal cancer is very poor. Therefore,
finding better cancer biomarkers to diagnose gastrointestinal malignancy and
predict patient survival is essential. HDAC1 has been reported to be closely
associated with several types of cancer, but the precise role of HDAC1 in
gastrointestinal cancer is not clear. Recently, quite a few studies have
investigated the correlation between HDAC1 expression and clinical features or
prognosis in multiple types of gastrointestinal malignancies, but the results
were inconsistent. In this study, we systematically reviewed the association
between HDAC1 and gastrointestinal malignancy using meta-analysis methods, and 28
eligible studies were analyzed. We found that the expression level of HDAC1 in
gastrointestinal malignancies, especially in colorectal cancer (OR = 10.84, 95%
CI = 5.33-22.07, P< 0.00001), was higher than that in noncancerous tissue, and
HDAC1 expression was closely associated with some clinical features of
gastrointestinal cancer patients, such as tumor stage (OR = 1.62, 95% CI = 1.28
2.05, P < 0.0001) and tumor grade (OR = 1.75, 95% CI = 1.03-2.95, P = 0.04). In
addition, we also found that patients with low HDAC1 expression showed better
overall survival than those with high HDAC1 expression in gastrointestinal
malignancy, especially in gastric cancer (HR = 1.88, 95% CI = 1.14-3.12, P =
0.01). Our results strongly suggest that HDAC1 may serve as a good diagnostic and
prognostic marker for gastrointestinal malignancy.
PMID- 28424408
TI - Synthetic lethality of glutaminolysis inhibition, autophagy inactivation and
asparagine depletion in colon cancer.
AB - Cancer cells reprogram metabolism to coordinate their rapid growth. They addict
on glutamine metabolism for adenosine triphosphate generation and macromolecule
biosynthesis. In this study, we report that glutamine deprivation retarded cell
growth and induced prosurvival autophagy. Autophagy inhibition by chloroquine
significantly enhanced glutamine starvation induced growth inhibition and
apoptosis activation. Asparagine deprivation by L-asparaginase exacerbated growth
inhibition induced by glutamine starvation and autophagy blockage. Similar to
glutamine starvation, inhibition of glutamine metabolism with a chemical
inhibitor currently under clinical evaluation was synthetically lethal with
chloroquine and L-asparaginase, drugs approved for the treatment of malaria and
leukemia, respectively. In conclusion, inhibiting glutaminolysis was
synthetically lethal with autophagy inhibition and asparagine depletion.
Therefore, targeting glutaminolysis could be a promising approach for colorectal
cancer treatment.
PMID- 28424409
TI - Clinical genomic profiling to identify actionable alterations for investigational
therapies in patients with diverse sarcomas.
AB - BACKGROUND: There are currently no United States Food and Drug Administration
approved molecularly matched therapies for sarcomas except gastrointestinal
stromal tumors. Complicating this is the extreme diversity, heterogeneity, and
rarity of these neoplasms. Few therapeutic options exist for relapsed and
refractory sarcomas. In clinical practice many oncologists refer patients for
genomic profiling hoping for guidance on treatment options after standard
therapy. However, a systematic analysis of actionable mutations has yet to be
completed. We analyzed genomic profiling results in patients referred to MD
Anderson Cancer Center with advanced sarcomas to elucidate the frequency of
potentially actionable genomic alterations in this population. METHODS: We
reviewed charts of patients with advanced sarcoma who were referred to
investigational cancer therapeutics department and had CLIA certified
comprehensive genomic profiling (CGP) of 236 or 315 cancer genes in at least 50ng
of DNA. Actionable alterations were defined as those identifying anti-cancer
drugs on the market, in registered clinical trials, or in the Drug-Gene
Interaction Database. RESULTS: Among the 102 patients analyzed median age was
45.5 years (range 8-76), M: F ratio 48:54. The most common subtypes seen in our
study were leiomyosarcoma (18.6%), dedifferentiated liposarcoma (11%),
osteosarcoma (11%), well-differentiated liposarcoma (7%), carcinosarcoma (6%),
and rhabdomyosarcoma (6%). Ninety-five out of 102 patients (93%) had at least one
genomic alteration identified with a mean of six mutations per patient. Of the 95
biopsy samples with identifiable genomic alterations, the most commonly affected
genes were TP53 (31.4%), CDK4 (23.5%), MDM2 (21.6%), RB1 (18.6%), and CDKN2A/B
(13.7%). Notable co-segregating amplifications included MDM2-CDK4 and FRS2-FGF.
Sixteen percent of patients received targeted therapy based on CGP of which 50%
had at least stable disease. CONCLUSIONS: Incorporating CGP into sarcoma
management may allow for more precise diagnosis and sub-classification of this
diverse and rare disease, as well as personalized matching of patients to
targeted therapies such as those available in basket clinical trials.
PMID- 28424411
TI - Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-,
and Hsp90-inhibition of glioblastoma cells with different invasive capacities.
AB - High invasiveness and resistance to chemo- and radiotherapy of glioblastoma
multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment
strategies for preventing migration and invasion of GBM cells are needed. Using
two different migration assays, Western blotting, conventional and super
resolution (dSTORM) fluorescence microscopy we examine the effects of the dual
PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP
AUY922 and/or irradiation on the migration, expression of marker proteins, focal
adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19)
markedly differing in their invasive capacity. Both lines were found to be
strikingly different in morphology and migration behavior. The less invasive DK
MG cells maintained a polarized morphology and migrated in a directionally
persistent manner, whereas the highly invasive SNB19 cells showed a multipolar
morphology and migrated randomly. Interestingly, a single dose of 2 Gy
accelerated wound closure in both cell lines without affecting their migration
measured by single-cell tracking. PI-103 inhibited migration of DK-MG (p53 wt,
PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells probably due to aberrant
reactivation of the PI3K pathway in SNB19 cells treated with PI-103. In contrast,
NVP-AUY922 exerted strong anti-migratory effects in both cell lines. Inhibition
of cell migration was associated with massive morphological changes and
reorganization of the actin cytoskeleton. Our results showed a cell line-specific
response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude that
anti-migratory agents warrant further preclinical investigation as potential
therapeutics for treatment of GBM.
PMID- 28424412
TI - FBXW7 missense mutation: a novel negative prognostic factor in metastatic
colorectal adenocarcinoma.
AB - BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant
oncogenic proteins and commonly mutates in colorectal cancer. Data suggest
missense mutations lead to greater loss of FBXW7 function than other gene
aberrations do. However, the clinicopathologic factors and outcomes associated
with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not
been described. METHODS: Data were obtained from mCRC patients whose tumors were
evaluated by next-generation sequencing for hotspot mutations at The University
of Texas MD Anderson Cancer Center. Alterations in FBXW7 were identified, and
their associations with clinicopathologic features and overall survival (OS) were
evaluated. RESULTS: Of 855 mCRC patients, 571 had data on FBXW7 status; 43 (7.5%)
had FBXW7 mutations, including 37 with missense mutations. R465C mutations in
exon 9 were the most common missense mutations (18.6%). PIK3CA mutations were
associated with FBXW7 missense mutations (p=0.012). On univariate analysis,
patients with FBXW7 missense mutations had significantly worse OS (median 28.7
mo) than those with wild-type FBXW7 (median 46.6 mo; p=0.003). On multivariate
analysis including other known prognostic factors such as BRAF mutations, FBXW7
missense mutations were the strongest negative prognostic factor for OS (hazard
ratio 2.0; p=0.003). CONCLUSIONS: In the largest clinical dataset of mCRC to
date, FBXW7 missense mutations showed a strong negative prognostic association.
PMID- 28424413
TI - The SNAIL/miR-128 axis regulated growth, invasion, metastasis, and epithelial-to
mesenchymal transition of gastric cancer.
AB - miR-128 is expressed in various tumors, but its expression and function in
gastric cancer have not been defined. Thus, the goal of this study was to
characterize miR-128 in gastric cancer. We found first that miR-128 is down
regulated in gastric cancer cell lines and tissues, and this dysregulation is
correlated with DNA methylation and the transcription factor SNAIL. Using
prediction tools, western blotting, and luciferase reporter assays, we found that
Bmi-1 was the direct target of miR-128. Additionally, overexpression of miR-128
inhibited gastric cancer cell migration, invasion, and proliferation by targeting
Bmi-1 in vitro and in vivo. We also documented, with receiver operating
characteristic curves and Kaplan-Meier survival analysis, that miR-128 and Bmi-1
may be useful markers for diagnosing and estimating the prognosis of gastric
cancer patients. As the epithelial-to-mesenchymal transition is an important
mechanism associated with cancer invasion and metastasis, we inferred that miR
128 could regulate this mechanism in gastric cancer. In fact, we found that miR
128 could reverse epithelial-to-mesenchymal transition induced by Bmi-1 via the
PI3K/AKT pathway. Because SNAIL also acts as a mesenchymal marker, our findings
identified a novel positive feedback loop in which the transcription factor SNAIL
curbs the expression of miR-128, and then down-regulated miR-128 promotes the
expression of Bmi-1; finally, overexpression of Bmi-1 drives the epithelial-to
mesenchymal transition process via the PI3K/AKT pathway, and the expression of
SNAIL is up-regulated.
PMID- 28424414
TI - Integrated analysis of promoter methylation and expression of telomere related
genes in breast cancer.
AB - Telomeres at the ends of eukaryotic chromosomes play a critical role in
tumorgenesis. Using microfluidic PCR and next-generation bisulfite sequencing
technology, we investigated the promoter methylation of 29 telomere related genes
in paired tumor and normal tissues from 184 breast cancer patients. The
expression of significantly differentially methylated genes was quantified using
qPCR method.We observed that the average methylation level of the 29 telomere
related genes was significant higher in tumor than that in normal tissues (P =
4.30E-21). A total of 4 genes (RAD50, RTEL, TERC and TRF1) showed significant
hyper-methylation in breast tumor tissues. RAD51D showed significant methylation
difference among the four breast cancer subtypes. The methylation of TERC showed
significant association with ER status of breast cancer. The expression profiles
of the 4 hyper-methylated genes showed significantly reduced expression in tumor
tissues. The integration analysis of methylation and expression of these 4 genes
showed a good performance in breast cancer prediction (AUC = 0.947).Our results
revealed the methylation pattern of telomere related genes in breast cancer and
suggested a novel 4-gene panel might be a valuable biomarker for breast cancer
diagnosis.
PMID- 28424415
TI - Clinicopathological features and outcome of chronic lymphocytic leukaemia in
Chinese patients.
AB - Chronic lymphocytic leukaemia (CLL) is uncommon in Chinese population and its
biology, genetics and treatment outcome in Chinese patients have not been
comprehensively investigated. In this study, we studied the clinicopathological
features and outcome of 212 Chinese patients with newly diagnosed CLL in Hong
Kong and Singapore. The median age at diagnosis was 64 years. The majority of
patients presented with early-stage disease (Binet stage A, 56.1%). Del(13)(q14)
was the most frequent abnormality (41.7%) detected by fluorescence in situ
hybridization (FISH) analysis. Del(17p) and TP53 gene mutations were detected in
7.8% and 8.2% of patients, respectively. MYD88 mutations were found at a higher
frequency (11.5%) than expected. CLL with unmutated variable region of the
immunoglobulin heavy chain genes (IGHV) occurred in only 31.2% of cases, and was
associated with advanced-stage disease (p <0.01) and adverse FISH abnormalities
(p<0.01). With a median follow-up of 39 months, the median overall survival (OS)
was 108 months. The presence of del(17p) or TP53 mutations was associated with a
significantly shorter time to first treatment and an inferior OS (p <0.01).
Unmutated IGHV was also associated with a significantly shorter time to treatment
(p <0.01). Among patients who required treatment, the median OS and progression
free survival (PFS) were 107 and 23 months, respectively. The presence of
del(17p) was associated with a significantly inferior OS and PFS (p <0.01). In
summary, Chinese CLL patients had similar genetic aberrations at diagnosis
compared with those of Western populations. FISH abnormalities are major factors
affecting outcome.
PMID- 28424416
TI - Loss of thyroid hormone receptor interactor 13 inhibits cell proliferation and
survival in human chronic lymphocytic leukemia.
AB - BACKGROUND: The genetic regulation of apoptosis and cell proliferation plays a
role in the growth of chronic lymphocytic leukemia (CLL), the most common form of
leukemia in the Western hemisphere. Although thyroid hormone receptor interactors
(TRIPs) are known to play roles in cell cycle, the potential involvement of the
novel family member TRIP13 in CLL has not yet been investigated. METHODS:
Quantitative PCR (qPCR) was used to detect expression of TRIP13 in 36 CLL
patients and 33 healthy donors CD19+ B cells. Loss-of-function (siRNA) assays
were used to alter TRIP13 expression levels. The effect of TRIP13 on cell
proliferation and apoptosis was measured by MTT, Annexin V-based flow cytometry
and Caspase 3/7 activity assay. Affymetrix GeneChip and Ingenuity Pathway
Analysis (IPA) were used to describe an overview of TRIP13 potential biological
function and downstream pathways. Dual-luciferase reporter assay was performed to
assess the promoting effect of c-MYC on TRIP13 transcription. RESULTS: The qPCR
data showed that TRIP13 is significantly over-expressed in CLL patients.
Microarray analyses indicated that the biological function of TRIP13 in CLL is
majorly cell apoptosis and cell proliferation associated. TRIP13 siRNA expressing
cells exhibited a slower cell proliferation rate and underwent apoptosis compared
with control cells. TRIP13 knockdown induced CLL cells apoptosis through PUMA
independent of p53. TRIP13 up-regulation is induced by c-MYC dependent
transcriptional activation. CONCLUSION: Overall, our data suggest the bio
function of TRIP13 in CLL cell for the first time, and that this gene might be a
therapeutic target for CLL.
PMID- 28424417
TI - Mesenchymal stem cells differentially affect the invasion of distinct
glioblastoma cell lines.
AB - Glioblastoma multiforme are an aggressive form of brain tumors that are
characterized by distinct invasion of single glioblastoma cells, which infiltrate
the brain parenchyma. This appears to be stimulated by the communication between
cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the
glioblastoma microenvironment, and their 'cross-talk' with glioblastoma cells is
still poorly understood. Here, we examined the effects of bone marrow-derived
MSCs on two different established glioblastoma cell lines U87 and U373. We
focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion
in three-dimensional invasion assays in vitro and in a zebrafish embryo model in
vivo. This is the first demonstration of glioblastoma cell-type-specific
responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the
invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross
talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC
enhanced invasion of U373 cells was assisted by overexpression of proteases
cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of
some of these proteases, as determined by the effects of their selective
inhibitors on invasion. In contrast, these proteases had no effect on U87 cell
invasion under MSC co-culturing. Finally, we identified differentially expressed
genes, in U87 and U373 cells that could explain different response of these cell
lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is
different in the two glioblastoma cell phenotypes, which contributes to tumor
heterogeneity.
PMID- 28424418
TI - The aryl hydrocarbon receptor is required for induction of p21cip1/waf1
expression and growth inhibition by SU5416 in hepatoma cells.
AB - The aryl hydrocarbon receptor (AhR) is a potential clinical target for cancer and
autoimmune dysfunction. Identifying selective AhR modulators that produce
desirable clinical outcomes represents an opportunity for developing new anti
cancer agents. Repurposing clinically-used drugs with established safety profiles
that activate the AhR represents a good starting place to pursue this goal. In
this study, we characterized the AhR-dependent effects of SU5416 (Semaxanib)
following its identification in a small-molecule library screen. SU5416 potently
activated AhR-dependent reporter genes, induced AhR nuclear localization,
facilitated AhR-DNA binding, and increased, expression of its endogenous target
genes. SU5416 significantly inhibited proliferation of Hepa1 hepatoma cells in an
AhR-dependent manner, but did not induce apoptosis. SU5416 also inhibited the
growth of human HepG2 liver cancer cells. The effects of SU5416 correlated with
an increased G1 population and increased expression of cell cycle inhibitor
p21cip1/waf1 at both the mRNA and protein level. Increased expression of
p21cip1/waf1 by SU5416 required expression of both AhR and Arnt. In addition,
evidence for long-term activation of the AhR in vivo by a single dose of SU5416
was identified by analyzing published microarray data. Our results provide
support for continued investigation of the AhR as therapeutic for cancers such as
hepatocellular carcinoma. In addition, our findings raise the possibility that
some of the previously observed anti-proliferative effects of SU5416 may be due
to activation of the AhR.
PMID- 28424419
TI - Integrated analysis of genes associated with poor prognosis of patients with
colorectal cancer liver metastasis.
AB - Colorectal cancer (CRC) is one of the most common malignances in the gut. Liver
is the most common metastasis site of CRC. This study focuses on the primary CRC
and its liver metastasis, aiming to discover several liver metastasis related
genes and provide therapeutic candidates. We compared gene expression patterns
among the groups of normal colorectal mucosa, primary tumor and the liver
metastasis using a CRC gene expression dataset. 84 genes were found to be
upregulated in both primary tumor and liver metastases. Function enrichment
analysis indicated that these genes are enriched in pathways such as chemotaxis,
coagulation and lipid metabolism which are crucial in multi-step cancer
metastasis. Gene network analysis identified several important hub genes that may
be involved in carcinogenesis and liver metastasis. Then we used a validation
dataset containing 562 CRC samples with detailed clinical information, to screen
prognostic biomarkers for overall survival (OS) and relapse free survival (RFS).
Finally, overexpression of THBS2 (thrombospondin 2), INHBB (inhibin, beta B) and
BGN (biglycan) were proved to be correlated with poor OS and RFS. In conclusion,
this study indicated that chemotaxis, coagulation and lipid metabolism might play
critical roles in the processes of carcinogenesis and liver metastasis. THBS2,
INHBB and BGN are prognostic markers and potential therapeutic targets for CRC.
PMID- 28424420
TI - Vitexin protects against hypoxic-ischemic injury via inhibiting Ca2+/Calmodulin
dependent protein kinase II and apoptosis signaling in the neonatal mouse brain.
AB - Neonatal hypoxic-ischemic is a major cause of death and disability in neonates.
In this study, we suggest for the first time that pretreatment with vitexin may
suppress a pro-apoptotic signaling pathway in hypoxic-ischemic neuronal injury in
neonates by inhibition of the phosphorylation of Ca2+/Calmodulin-dependent
protein kinase II. Here we found that vitexin pretreatment reduced brain infarct
volume in a dose-dependent manner. In addition, vitexin decreased the number of
TUNEL-positive cells and brain atrophy. Furthermore, vitexin improved
neurobehavioral outcomes. Vitexin also reduced oxygen glucose deprivation-induced
neuronal injury and calcium entry. Vitexin pretreatment increased the Bcl-2/Bax
protein ratio and decreased phosphorylation of Ca2+/Calmodulin-dependent protein
kinase II and NF-kappaB, cleaved caspase-3 protein expression 24 hours after
injury. Our data indicate that pretreatment with vitexin protects against
neonatal hypoxic-ischemic brain injury and thus has potential as a treatment for
hypoxic-ischemic brain injury.
PMID- 28424421
TI - The soy-derived peptide Lunasin inhibits invasive potential of melanoma
initiating cells.
AB - Lunasin is a 44 amino acid peptide with multiple functional domains including an
aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We
recently showed that Lunasin induced a phenotype switch of cancer initiating
cells (CIC) out of the stem compartment by inducing melanocyte-associated
differentiation markers while simultaneously reducing stem-cell-associated
transcription factors. In the present study, we advance the hypothesis that
Lunasin can reduce pools of melanoma cells with stem cell-like properties, and
demonstrate that Lunasin treatment effectively inhibits the invasive potential of
CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice
receiving Lunasin treatment had significantly reduced pulmonary colonization
after injection of highly metastatic B16-F10 melanoma cells compared to mice in
the control group. Mechanistic studies demonstrate that Lunasin reduced
activating phosphorylations of the intracellular kinases FAK and AKT as well as
reduced histone acetylation of lysine residues in H3 and H4 histones. Using
peptides with mutated activity domains, we functionally demonstrated that the RGD
domain is necessary for Lunasin uptake and its ability to inhibit oncosphere
formation by CICs, thus confirming that Lunasin's ability to affect CICs is at
least in part due to the suppression of integrin signaling. Our studies suggest
that Lunasin represents a unique anticancer agent that could be developed to help
prevent metastasis and patient relapse by reducing the activity of CICs which are
known to be resistant to current chemotherapies.
PMID- 28424422
TI - Limited impact of intratumour heterogeneity on molecular risk assignment in
endometrial cancer.
AB - INTRODUCTION: Individual prediction of tumour behaviour based on molecular
markers may refine adjuvant treatment strategies in endometrial cancer (EC). As
these molecular alterations are determined in a small tumour fraction, high
intratumour heterogeneity may interfere with correct risk prediction. This study
aimed to investigate to which extent intratumour heterogeneity exists for
molecular markers and whether it affects the molecular risk assignment in EC.
METHODS: Forty-nine ECs (three tumour blocks/case) were selected with alterations
in POLE (n=10), CTNNB1 (n=8), p53 (n=10), mismatch repair (n=11), L1CAM (n=10),
and ECs without any of these markers (n=9). Nine ECs carried more than one
molecular marker. All 147 blocks were analysed for POLE exonuclease domain and
CTNNB1 exon 3 mutations, and for p53, mismatch repair and L1CAM protein
expression. All blocks were assigned to a favourable, intermediate or
unfavourable risk group, based on a molecular risk assignment. RESULTS:
Concordance between the three tumour blocks for POLE and CTNNB1 mutational
status, and p53, mismatch repair and L1CAM protein expression was found in 100%
(48/48), 95.9% (47/49), 93.9% (46/49), 98.0% (48/49), and 91.8% (45/49) of
tumours, respectively. These discordances were found in a total of nine cases
(18.4%). The intratumour heterogeneity impacted the risk assignment in five cases
(10.2%). CONCLUSION: Intratumour heterogeneity of prognostic molecular markers in
EC without morphologic heterogeneity is uncommon among three tumour fractions,
affecting the molecular risk allocation in a limited number of cases. This low
intratumour heterogeneity facilitates the implementation of the molecular risk
assignment, advocating its use in clinical decision making.
PMID- 28424423
TI - The antidepressant-like effect of trans-astaxanthin involves the serotonergic
system.
AB - The antidepressant-like effect of trans-astaxanthin, a compound present rich in
algae, was evaluated through behavioral and neurochemical methods. Results showed
that trans-astaxanthin treatment significantly decreased the immobility time in
force swim test and tail suspension test, but did not influence locomotor
activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia
and ptosis induced by reserpine. However, pre-treatment with para
chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in
force swim and tail suspension test. These results suggested that the mechanism
of antidepressant-like effect of trans-astaxanthin may involve the serotonergic
system, but not noradrenaline system. This hypothesis was confirmed by
neurochemical assays which showed that trans-astaxanthin increased serotonin
levels in the hippocampus, frontal cortex, striatum and hypothalamus.
Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3
dioxygenase activity in the hippocampus, frontal cortex and hypothalamus.
Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the
kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these
brain regions. Taken together, these findings indicate that the antidepressant
like effect of trans-astaxanthin involves the serotonergic system.
PMID- 28424424
TI - Leukocyte telomere length-related genetic variants in ACYP2 contribute to the
risk of esophageal carcinoma in Chinese Han population.
AB - BACKGROUND: Short leukocyte telomere length has been associated with
significantly increased risk of esophageal carcinoma. A previous genome-wide
association study demonstrated that ACYP2 was associated with leukocyte telomere
length. However, the role of ACYP2 genetic variants on esophageal carcinoma
susceptibility is still unknown. Therefore, we investigated whether ACYP2
polymorphisms have impact on the risk of esophageal carcinoma in Chinese.
MATERIALS AND METHODS: We conducted a case-control study among 386 cases and 495
healthy controls from northwest China. 14 SNPs in ACYP2 were selected and
genotyped using Sequenom MassARRAY technology. Odds ratios (OR) and 95%
confidence intervals (CIs) were calculated by unconditional logistic regression
adjusting for age and gender. RESULTS: We found that 1.34-fold increased risk of
esophageal carcinoma is associated with the rs11125529 A allele compared with the
rs11125529 C allele (OR=1.29, 95%CI: 1.02-1.62, p=0.030) under the additive
model, after adjusted by age and gender. We also found rs11896604 and rs17045754
loci increased the esophageal carcinoma risk under the additive model
(rs11896604: OR=1.34, 95%CI: 1.03-1.76, p=0.032; rs17045754: OR=1.36, 95%CI: 1.03
1.80, p=0.028). One main linkage block was observed across the locus. This block
was comprised of seven closely linked SNPs: rs1682111, rs843752, rs10439478,
rs843645, rs11125529, rs843711 and rs11896604. The haplotype analysis detected
that haplotype "TTCTATG" increased the risk of esophageal carcinoma (OR=1.38,
95%CI: 1.04-1.82, p=0.025). CONCLUSION: In conclusion, ACYP2 gene may be
associated with an increased risk of esophageal carcinoma in Chinese Han
populations. Future studies to address the biological function of this
polymorphism in the development of esophageal carcinoma are warranted.
PMID- 28424426
TI - Circular RNA hsa-circ-0016347 promotes proliferation, invasion and metastasis of
osteosarcoma cells.
AB - Circular RNAs (circRNAs) are a novel class of non-coding RNA which have recently
shown huge capabilities in the regulation of gene expression at the post
transcriptional level. Growing evidence has indicated that circRNAs could serve
as competing endogenous RNAs (ceRNAs) to bind with microRNAs (miRNAs) and to
inhibit the activity and function of the targeted miRNAs. Here, we demonstrated
that circ-0016347 acted as a positive regulator in osteosarcoma cells
proliferation and invasion. Moreover, circ-0016347 was identified as a sponge of
miR-214 that upregulated the expression of caspase-1, which is the functional
target of miR-214. Our study provides novel insight into the regulatory mechanism
of circ-0016347 and its downstream targets in proliferation, invasion and
metastasis of osteosarcoma cells, which will facilitate further development in
the therapy of osteosarcoma.
PMID- 28424427
TI - NOS2 expression in glioma cell lines and glioma primary cell cultures:
correlation with neurosphere generation and SOX-2 expression.
AB - Nitric oxide has been implicated in biology and progression of glioblastoma (GBM)
being able to influence the cellular signal depending on the concentration and
duration of cell exposure. NOS2 (inducible nitric oxide synthase) have been
proposed as a component of molecular profile of several tumors, including glioma,
one of the most aggressive primary brain tumor featuring local cancer stem cells
responsible for enhanced resistance to therapies and for tumor recurrence. Here,
we investigated the NOS2 mRNA expression by reverse transcription-PCR in human
glioma primary cultures at several grade of malignancy and glioma stem cell (GSC)
derived neurospheres. Glioma cell lines were used as positive controls both in
terms of stemness marker expression that of capacity of generating neurospheres.
NOS2 expression was detected at basal levels in cell lines and primary cultures
and appeared significantly up-regulated in cultures kept in the specific medium
for neurospheres. The immunofluorescence analysis of all cell cultures to
evaluate the levels of SOX-2, a stemness marker aberrantly up-regulated in GBM,
was also performed. The potential correlation between NOS2 expression and ability
to generate neurospheres and between NOS2 and SOX-2 levels was also verified. The
results show that the higher NOS2 expression is detected in all primary cultures
able to arise neurosphere. A high and significant correlation between NOS2
expression and SOX-2 positive cells (%) in all cell cultures maintained in
standard conditions has been observed. The results shed light on the potential
relevance of NOS2 as a prognostic factor for glioma malignancy and recurrence.
PMID- 28424429
TI - The volatile molecule signature of four mycobacteria species.
AB - Mycobacteria are the leading cause of death from infectious disease worldwide and
limitations in current diagnostics are hampering control efforts. In recent
years, the use of small volatile molecules as diagnostic biomarkers for
mycobacteria has shown promise for use in the rapid analysis of in vitro cultures
as well as ex vivo diagnosis using breath or sputum. In this study, 18 strains
from four mycobacteria species (Mycobacterium avium, M. bovis BCG, M.
intracellulare and M. xenopi) were analyzed for the first time using two
dimensional gas chromatography time-of-flight mass spectrometry (GC * GC-TOFMS).
This study represents the first time volatile molecules associated with M.
intracellulare and M. xenopi have ever been reported. A total of 217
chromatographic features were identified and 58 features were selected that
discriminate between these four species. Putative identifications are provided
for 17 of the 58 discriminatory features, three of which have been reported
previously in mycobacteria. The identification of mycobacteria-associated
volatile biomarker suites could reduce the time-to-diagnosis for mycobacterial
infections, either from in vitro cultures prior to the visualization of colonies
or directly from ex vivo specimens, thereby shortening the empiric treatment
window and potentially improving outcomes.
PMID- 28424428
TI - Global miRNA expression profiling of domestic cat livers following acute
Toxoplasma gondii infection.
AB - Although microRNAs (miRNAs) play an important role in liver homeostasis, the
extent to which they can be altered by Toxoplasma gondii infection is unknown.
Here, we utilized small RNA sequencing and bioinformatic analyses to characterize
miRNA expression profiles in the liver of domestic cats at 7 days after oral
infection with T. gondii (Type II) strain. A total of 384 miRNAs were identified
and 82 were differentially expressed, of which 33 were up-regulated and 49 down
regulated. Also, 5690 predicted host gene targets for the differentially
expressed miRNAs were identified using the bioinformatic algorithm miRanda. Gene
ontology analysis revealed that the predicted gene targets of the dysregulated
miRNAs were significantly enriched in apoptosis. Kyoto Encyclopedia of Genes and
Genomes analysis showed that the predicted gene targets were involved in several
pathways, including acute myeloid leukemia, central carbon metabolism in cancer,
choline metabolism in cancer, estrogen signaling pathway, fatty acid degradation,
lysosome, nucleotide excision repair, progesterone-mediated oocyte maturation,
and VEGF signaling pathway. The expression level of 6 upregulated miRNAs (mmu-miR
21a-5p, mmu-miR-20a-5p, mmu-miR-17-5p, mmu-miR-30e-3p, mmu-miR-142a-3p, and mmu
miR-106b-3p) was confirmed by stem-loop quantitative reverse transcription PCR,
which yielded results consistent with the sequencing data. These findings expand
our understanding of the regulatory mechanisms of miRNAs underlying T. gondii
pathogenesis and contribute new database information on cat miRNAs, opening a new
perspective on the prevention and treatment of T. gondii infection.
PMID- 28424430
TI - Exploring non-stationarity patterns in schizophrenia: neural reorganization
abnormalities in the alpha band.
AB - OBJECTIVE: The aim of this paper was to characterize brain non-stationarity
during an auditory oddball task in schizophrenia (SCH). The level of non
stationarity was measured in the baseline and response windows of relevant tones
in SCH patients and healthy controls. APPROACH: Event-related potentials were
recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in
the conventional electroencephalography frequency bands by means of Kullback
Leibler divergence (KLD). Relative power (RP) was also computed to assess a
possible complementarity with KLD. MAIN RESULTS: Results showed a widespread
statistically significant increase in the level of non-stationarity from baseline
to response in all frequency bands for both groups. Statistically significant
differences in non-stationarity were found between SCH patients and controls in
beta-2 and in the alpha band. SCH patients showed more non-stationarity in the
left parieto-occipital region during the baseline window in the beta-2 band. A
leave-one-out cross validation classification study with feature selection based
on binary stepwise logistic regression to discriminate between SCH patients and
controls provided a positive predictive value of 72.73% and negative predictive
value of 78.95%. SIGNIFICANCE: KLD can characterize transient neural
reorganization during an attentional task in response to novelty and relevance.
Our findings suggest anomalous reorganization of neural dynamics in SCH during an
oddball task. The abnormal frequency-dependent modulation found in SCH patients
during relevant tones is in agreement with the hypothesis of aberrant salience
detection in SCH. The increase in non-stationarity in the alpha band during the
active task supports the notion that this band is involved in top-down
processing. The baseline differences in the beta-2 band suggest that
hyperactivation of the default mode network during attention tasks may be related
to SCH symptoms. Furthermore, the classification improved when features from both
KLD and RP were used, supporting the idea that these measures can be
complementary.
PMID- 28424431
TI - [2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: What is new?]
PMID- 28424432
TI - [Prevalence of HIV infection in Turkey and importance of cardiovascular disease].
PMID- 28424433
TI - [Investigating the role of ceramide metabolism-associated CERS5 (LASS5) gene in
atherosclerosis pathogenesis in endothelial cells].
AB - OBJECTIVE: Ceramide, the backbone of sphingolipids, is the key component
affecting atherosclerotic changes through its important second-messenger role.
Previous studies have demonstrated protective role of AMP-activated protein
kinase (AMPK) genes in regulating atherosclerosis and hypertension. Ceramide
synthase 5 (LASS5 or CERS5) gene has function in de novo synthesis of ceramide,
and has indirect effect on AMPK gene. Aim of the present study was to identify
role of LASS5 gene in atherosclerosis. METHODS: LASS5 gene-specific small
interfering RNA (siRNA)-mediated gene silencing was performed in human umbilical
vein endothelial cells (HUVEC) and differential expression of LASS5, AMPK-alpha
and AMPK-alpha target genes were analyzed. HUVEC cells were then treated with
AMPK activator in order to examine relationship of change in gene expression
levels to AMPK activity. RESULTS: Novel physiological function of LASS5 was
identified. Downregulation of LASS5 was found to attenuate ceramide production
and increase expression of some AMPK target genes in HUVEC. CONCLUSION: This is
the first study to demonstrate that LASS5 was involved in negative regulation of
atherosclerosis-related genes, such as AMPK-alpha. These preliminary findings
provide insight into molecular mechanism of atherosclerosis and are important for
development of potential therapeutic agents in the treatment of atherosclerosis.
PMID- 28424434
TI - High-dose bolus tirofiban versus low-dose bolus in patients with acute coronary
syndrome undergoing percutaneous coronary intervention.
AB - OBJECTIVE: Aim of the present study was to determine effects of high-dose versus
low-dose intravenous (IV) bolus tirofiban on angiographic measures, ST
resolution, enzymatic infarct size, and clinical outcomes in patients with acute
coronary syndrome (ACS) who were undergoing percutaneous coronary intervention
(PCI) and received current pharmacoinvasive therapy. METHODS: Acute coronary
syndrome patients (n=271, 85.6% male; mean age: 57.9+/-12.6 years) from between
2009 and 2015 who received IV tirofiban therapy following PCI were
retrospectively analyzed. All patients had received maintenance tirofiban
infusion (0.15 ug/kg/min) after bolus dose and 600 mg clopidogrel. Percentage of
patients undergoing drug eluting stent implantation procedure was 33.5%.
Tirofiban was administered to all patients in bailout situation or for thrombotic
complication after PCI. RESULTS: High-dose IV bolus group (25 ug/kg; n=140) was
associated with greater ST segment resolution (66% vs. 50%, p=0.013) and reduced
peak troponin release [12.4 ng/dL (range: 6.5-21.5 ng/dL) vs. 16.4 ng/dL (range:
10.1-27.4 ng/dL), p=0.001] compared with low-dose bolus group (10 ug/kg, n=131).
Cardiovascular event rates were similar between groups at in-hospital, 1-month,
and 6-month follow-up (p=1.000, 1.000, and 0.287, respectively). Percentage of
patients with post-procedural Thrombolysis in Myocardial Infarction (TIMI) grade
III flow, major, and minor bleeding were similar (p=0.085, 1.000, and 0.965,
respectively). CONCLUSION: Use of high-dose IV bolus tirofiban in addition to
aspirin and high-dose clopidogrel improves ST segment resolution, reduces infarct
size, and does not increase bleeding events in patients with ACS undergoing PCI
compared with low-dose bolus. Angiographic measures and clinical endpoints were
similar between groups.
PMID- 28424435
TI - [EUROASPIRE-IV: European Society of Cardiology study of lifestyle, risk factors,
and treatment approaches in patients with coronary artery disease: Data from
Turkey].
AB - OBJECTIVE: Data from EUROASPIRE-IV Turkey report investigating risk factors and
adherence to guidelines in patients hospitalized for coronary artery disease are
presented and results are compared with those of EUROASPIRE-III Turkey and
EUROASPIRE-IV Europe. METHODS: Study was performed in 24 European countries,
including Turkey (17 centers). Patients (18-80 years old) hospitalized for
coronary (index) event during preceding 3 years were identified from hospital
records and interviewed >=6 months later. Patient information regarding index
event was acquired from hospital records. Anamnesis was obtained during the
interview, and physical examination and laboratory analyses were performed.
RESULTS: Median age at the index coronary event was 58.8 years, and it was
significantly decreased compared with last EUROASPIRE-III study (60.5 years),
which was conducted at the same centers 6 years earlier (p=0.017). Of all
patients, 19.3% were under 50 years of age and mean age was lower than that of
EUROASPIRE-IV Europe (62.5 years). Comparing EUROASPIRE-IV Turkey with EUROASPIRE
III Turkey, rate of smokers increased to 25.5% from 23.1% (p=0.499), obesity
increased to 40.7% from 35.5% (p=0.211), total cholesterol level increased to
49.6% from 48.3% (p=0.767), and diabetes rate increased to 39.7% from 33.6%
(p=0.139), however none of the differences reached a level of statistical
significance. Only 11.7% of the smokers quit after coronary event. Rates for
these factors were lower in EUROASPIRE-IV Europe (16% for smoking, 37.6% for
obesity, and 26.8% for diabetes). CONCLUSION: EUROASPIRE-IV Turkey data revealed
that secondary prevention was unsatisfactory and had progressed unfavorably
compared with last EUROASPIRE study, some risk factors were more uncontrolled
than overall European average, and coronary artery events at young age remain an
important problem.
PMID- 28424436
TI - [Dyslipidemia and cardiovascular risk assessment in HIV-positive patients].
AB - OBJECTIVE: Dyslipidemia is a major complication of antiretroviral treatment. Aim
of the present study was to screen baseline lipid levels and cardiovascular
disease risk in HIV-positive patients and analyze change in those parameters
after initiation of antiretroviral treatment (ART). METHODS: HIV-positive
patients who presented at our clinic between April 2011 and August 2012 were
included. Study included 19 female (22.1%) and 67 male (77.9%) patients (mean age
39.5+/-10.3 years). Blood pressure, smoking habit, alcohol consumption, serum
total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low
density lipoprotein (LDL), glucose level, and antiretroviral treatment status
data were reviewed retrospectively. Changes in lipid profile and lifetime risk
for atherosclerotic cardiovascular disease (ASCVD) according to the American
College of Cardiology guidelines were compared with baseline data and analyzed.
RESULTS: At baseline, 13 (15.1%) patients were already receiving ART and 73
(84.9%) patients were treatment-naive or had stopped therapy >=3 months prior to
enrollment. At last visit, 73 (84.9%) patients were taking ART. Results of
baseline and final visit TC levels were 175.5 mg/dL (range: 90-346 mg/dL) and
196.5 mg/dL (range: 104-317 mg/dL), respectively (p=0.001). HDL levels were 40
mg/dL (range: 21-81 mg/dL) and 35 mg/dL (range: 10-75 mg/dL; p=0.001), and LDL
levels were 101.5 mg/dL (range: 32-191 mg/dL) and 120.5 mg/dL (range: 32-250
mg/dL; p<0.001). TG levels were 145.5 mg/dL (range: 43-2580 mg/dL and 152.5 mg/dL
(range: 67-884 mg/dL; p=0.102). Baseline ASCVD risk score was 46% (range: 5-69%)
while last visit ASCVD risk score was 50% (range: 5-69%; p<0.001). CONCLUSION:
HIV infection has adverse effects on lipid profiles and cardiovascular risk of
HIV-positive patients. Therefore, patients should be closely monitored for
lifestyle interventions and lipid-lowering agents.
PMID- 28424437
TI - [The effects of coronary artery disease severity on left atrial deformation
parameters in patients with stable coronary artery disease].
AB - OBJECTIVES: Aim of the present study was to investigate correlation between left
atrial (LA) deformation parameters assessed using 2-dimensional (2D) speckle
tracking echocardiography (STE) and complexity of coronary artery disease
according to SYNTAX score (SXscore) in patients with stable coronary artery
disease (SCAD). STUDY DESIGN: Total of 60 moderate-risk SCAD patients (40 men, 20
women) who underwent coronary angiography and 30 healthy controls were included.
Measurements of conventional echocardiographic parameters as well as peak LA
strain during ventricular systole (LA-RES), peak LA strain during atrial systole
(LA-PUMP), peak LA strain rate during ventricular systole (LA-SRS), peak LA
strain rate during early diastole (LA-SRE), and peak LA strain rate during atrial
systole (LA-SRA) were obtained. RESULTS: Patients were categorized into 2 groups:
low SXscore of <20 (Group I) and high SXscore of >=20 (Group II). Left
ventricular (LV) diastolic functions were significantly impaired and LV filling
pressure was significantly higher in high SXscore group. LA-RES (Control Group:
42.3+/-7.9, Group I: 36.4+/-8.2, Group II: 27.5+/-8.1; p<0.001) and LA-PUMP
(Control Group: 17.6+/-3.4, Group I: 15.7+/-2.5, Group II: 13.1+/-3.2; p<0.001)
were significantly lower in high SXscore group compared with low SXscore group.
There was no statistical difference in LA-SRS, LA-SRE, or LA-SRA between the 3
groups. Correlation analysis indicated negative correlation between SXscore level
and LA-RES function (r=-0.49; p<0.001). CONCLUSION: 2D-STE-based LA deformation
parameters are significantly impaired in patients with SCAD who have high
SXscore. In addition, evaluation of LA-RES and LA-PUMP functions might be useful
in estimating severity of disease in patients with SCAD.
PMID- 28424438
TI - Using cardiovascular imaging modalities to determine cardiac disorders before
starting sports activities.
AB - OBJECTIVE: We re-examined children who had previously been declared eligible to
participate in competitive sports activities for cardiac disorders, using cardiac
investigation protocol. METHODS: Total of 250 children (224 males [89.6%], and 26
females [10.4%]) between the ages of 8 and 17 years who had just started or were
already engaged in sports activities were included in the study. Participants had
detailed physical examination evaluated by a pediatric cardiologist. Those with
findings suggesting cardiac disorder in their history and/or physical
examinations, and/or 12-channel electrocardiography (ECG) were examined with
echocardiography (ECHO), 24-hour Holter monitoring, and exercise test. RESULTS:
Mean duration of participation in sports activities was 13 months. Among all,
10.4% of the children had abnormalities on ECG. ECHO demonstrated cardiomyopathy
in 1, mitral valve prolapse in 2, tricuspid insufficiency in 2, and mitral
insufficiency in 1 participant. Holter monitoring revealed non-sustained
ventricular tachycardia attacks in 1, and supraventricular tachycardia in another
child. Three were ultimately disqualified from partaking in competitive sports.
CONCLUSION: Sports and medical communities must work together to establish study
protocols to prevent sudden death related to sports and to make these activities
safer for athletes. Pediatric cardiology consultation for young athletes before
they start sports activities is needed.
PMID- 28424439
TI - Management of immediate partial bioresorbable vascular scaffold stent thrombosis.
AB - Bioresorbable vascular scaffold (BVS) stents have been proposed recently as an
elegant technique for treatment of coronary artery disease. However, perspective
that these "dissolvable" stents will replace conventional metallic stents in
broad spectrum of clinical conditions and patient categories in the near future
has been moderated by non-negligible incidence of stent thrombosis (ST).
Mechanical factors, such as strut thickness and malapposition have been
implicated in increased risk of BVS ST. Presently described is case of immediate
partial BVS ST in a young male related to technical procedural problem, rather
than mechanical problem. Glycoprotein IIb/IIIa inhibitors associated with
anticoagulation resulted in complete resolution of thrombus and facilitated
successful patient outcome.
PMID- 28424440
TI - Gemcitabine-induced coronary vasospasm: A case report.
AB - Gemcitabine is a chemotherapy drug. It is a nucleoside analogue that is usually
well tolerated by patients, with myelosuppression (especially thrombocytopenia)
as dose-limiting side effect. Other mild to moderate side effects include
alopecia, vomiting, nausea, rash, and fever. Coronary ischemia is the most common
cardiotoxic effect of gemcitabine, which is due to its antimetabolites. While
underlying cause of coronary ischemia following use of gemcitabine is uncertain,
endothelial dysfunction and coronary thrombosis are potential explanations. To
our knowledge, there are few published case reports of adverse cardiovascular
side effects associated with gemcitabine. Presently described is case of acute
inferior myocardial infarction in a female patient caused by gemcitabine.
PMID- 28424441
TI - Spontaneous echocardiographic contrast due to ductus venosus.
AB - Spontaneous echocardiographic contrast is defined as a phenomenon of discrete
reflections appearing in the cardiac chambers or great vessels. It has been
associated with several conditions leading to microbubble formation or low blood
flow. This is a report of a neonate with spontaneous echocardiographic contrast
related to patent ductus venosus.
PMID- 28424442
TI - Clinical improvement and no further need of transplant after closure of PDA with
transcatheter approach in an end-stage heart failure patient with
hypertrabeculation.
AB - Although heart failure is managed medically most of the time, heart
transplantation is still last resort for selected end-stage heart failure
patients with noncompaction cardiomyopathy. Presently described for the first
time is case of pediatric patient with noncompaction cardiomyopathy who was
initially referred to our hospital for heart transplant but underwent PDA repair
and improved clinically without need for heart transplant.
PMID- 28424443
TI - Case report of a rarely seen long-segment middle aortic syndrome.
AB - Middle aortic syndrome (MAS) follows a course with distal thoracic and abdominal
aorta stenosis. It is a rare disease that is usually diagnosed after the first
decade of life. Clinical reflection of MAS is often in the form of hypertension
and claudication in the lower extremities. Its etiology is unclear, but is known
to be associated with congenital or acquired diseases. This pathology, which is
accompanied by malignant hypertension, often does not respond to medical
treatment. In patients with MAS, surgical treatment is first line recommendation
to prevent complications such as hypertension, heart failure, intracranial
bleeding, or aortic rupture. In order to draw attention to this disease,
presently described is case of high blood pressure detected during routine
examination of a child who had no complaint, and discovery of long-segment
stenosis in the abdominal aorta identified with echocardiography and conventional
angiography.
PMID- 28424444
TI - A successful cesarean delivery without fetal or maternal morbidity in an
Eisenmenger patient with cor triatriatum sinistrum, double-orifice mitral valve,
large ventricular septal defect, and single ventricle who was under long-term
bosentan treatment.
AB - Presently described is successful cesarean delivery in a pregnancy superimposed
on long-term bosentan treatment in an Eisenmenger syndrome patient with cor
triatriatum sinistrum, double-orifice mitral valve, and large ventricular septal
defect resulting in single functioning ventricle with double outlets. Cesarean
delivery was performed at 27th week of gestation without maternal or fetal
morbidity. The infant had no congenital cardiovascular abnormality or any
probable teratogenic effect of bosentan treatment during pregnancy.
PMID- 28424445
TI - Management of tachyarrhythmia during pregnancy.
AB - Maternal tachyarrhythmia is a common complication during pregnancy due to
hormonal changes that enhance pre-existing arrhythmias or induce new arrhythmias
in the presence of congenital heart defects in pregnant females. Presence of
tachyarrhythmia during pregnancy poses risk to the mother and fetus, calling for
proper treatment with medications. Use of antiarrhythmic drugs in cases of
maternal tachyarrhythmia must give due consideration of potential teratogenic
side effects. Utilization of antiarrhythmic drugs during pregnancy has been well
studied; some result in minimal fetal harm or none at all. New techniques, such
as cardiac ablation, have also been implemented with minimal or no radiation
exposure to the fetus or mother. Pregnant women with tachyarrhythmia have been
successfully treated with little to no impact on the developing fetus as result
of increasing experience with antiarrhythmic drugs and progress of new procedural
techniques.
PMID- 28424446
TI - Speckle tracking strain imaging: Practical approach for application.
PMID- 28424447
TI - Case images: Detection and management of ICD lead implanted in middle cardiac
vein.
PMID- 28424448
TI - Case images: Treatment of thrombotic subclavian artery stenosis involving
vertebral artery ostium with maximum protection.
PMID- 28424449
TI - Case images: Electrical isolation of superior vena cava as well as pulmonary vein
isolation with cryoballoon technique in a young patient with persistent atrial
fibrillation.
PMID- 28424450
TI - Case images: A rare complication of infective endocarditis: Ruptured
pseudoaneurysm of mitral-aortic interventricular fibrosa.
PMID- 28424451
TI - Prognostic impact of NOTCH1, MYD88, and SF3B1 mutations in Polish patients with
chronic lymphocytic leukemia.
AB - INTRODUCTION Currently available prognostic factors determining the course of
chronic lymphocytic leukemia (CLL) are not fully efficient, especially for newly
diagnosed patients. Investigation of molecular changes may help clarify the
reasons for the heterogeneity of the disease. Apart from already confirmed TP53
mutations, the novel candidates: NOTCH1, SF3B1, and MYD88 might represent
clinically relevant biomarkers. OBJECTIVES The aim of this study was to
evaluate the mutational status of NOTCH1, MYD88, and SF3B1 and to compare the
results with confirmed prognostic factors: ZAP-70, CD38, and immunoglobulin heavy
chain variable region (IGHV) mutation in CLL. The study assessed also prognostic
significance in terms of the time to first treatment (TTFT) and subset analysis.
PATIENTS AND METHODS The study was conducted on samples of 370 newly diagnosed
patients with CLL. The analysis was performed using high-resolution melting,
Sanger sequencing, and polymerase chain reaction methods. RESULTS Patients
harboring the NOTCH1 mutation were significantly more often found among patients
with an unmutated IGHV gene status and high expression of CD38 and ZAP-70. The
MYD88 mutation was equally distributed in patients with mutated and unmutated
IGHV status (5 vs 7 patients). For MYD88 and SF3B1, there were no significant
differences in the levels of CD38 and ZAP-70 expression. The tendency for lower
median TTFT was revealed in patients with mutated SF3B1 (P = 0.08). The analysis
showed the presence of 14 different types of the subsets of IGHV in 50 of 345
patients (14.5%). The most frequent were subsets #1 and #2. CONCLUSIONS The
NOTCH1 and SF3B1 mutations accompany biological markers of unfavorable prognosis
in patients with CLL. The mutations may contribute to the identification of
patients with high-risk CLL.
PMID- 28424452
TI - Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C
Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined
Signaling Route Would Induce Alternative Consideration to Previous Conceptions.
AB - BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent,
after binding to its receptor PTHR1, several signaling pathways, including
cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are
initiated through G proteins; with the cAMP/PKA pathway as the major pathway.
Earlier studies have reported that PTHR1 might also activate PKC via a PLC
independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In
HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with
fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In
MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then
assays for cell apoptosis, cell differentiation, alkaline phosphatase activity,
and mineralization were performed. RESULTS The FRET analysis found that PTH(1
34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all
activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP
inhibitor (Rp-cAMP) and rescued with the addition of active PKA-alpha and PKA
beta. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP.
In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was
regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983.
After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG
were differentially regulated by GR(1-28) or GR(1-34), and the difference was
blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased
early apoptosis and augmented osteoblastic differentiation in accordance with the
activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by
PTH could be divided into two potential mechanisms: one was PKA-dependent and
associated with PTH(1-28); the other was PKA-independent and associated with
PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA
dependent mechanisms.
PMID- 28424453
TI - Comorbid Human Immunodeficiency Virus (HIV) and Muscle-Specific Kinase (MuSK)
Myasthenia Gravis: A Case Report and Literature Review.
AB - BACKGROUND HIV infections with concomitant immunologically-mediated disorders
have been frequently described but there has been little research on the
association between HIV and myasthenia gravis. MuSK myasthenia gravis coexisting
with HIV is an even a rarer entity and can occur as a part of immune restoration
disease. We report the case of a patient with asymptomatic HIV infection who
presented with new-onset MuSK myasthenia gravis. CASE REPORT A 44-year-old
African-American woman with HIV since 2004 and on highly active antiretroviral
therapy (HAART) presented to the ED with complains of double vision and
difficulty swallowing for 2 weeks. The patient was intermittently on HAART
therapy. On examination, she had bilateral ptosis, weak orbicularis oris and
orbicularis oculi, along with mild lateral gaze palsy of the left eye. Her CD4
count was 383 and the viral load was undetectable. An MRI of the brain produced
normal results and a CT chest did not show thymus enlargement. Due to worsening
symptoms and high suspicion for myasthenia gravis, she was started on IVIG at 0.4
mg/kg/day for 5 days, and her symptoms markedly improved. She was found to have
strongly positive MuSK antibody and negative Ach receptor antibody. Repetitive
nerve stimulation showed a 13% decrease in the right median nerve, which
confirmed the diagnosis. She was subsequently discharged to home on
pyridostigmine. Azathioprine was added at clinic follow-up. The patient continues
to improve. CONCLUSIONS As the use of antiretroviral therapy increases, immune
reconstitution syndromes have become more common. Rare associations like HIV and
MuSK myasthenia gravis are being increasingly reported. The use of
immunosuppressants in the treatment of these conditions should be carefully
evaluated.
PMID- 28424454
TI - Inference of the infection status of individuals using longitudinal testing data
from cryptic populations: Towards a probabilistic approach to diagnosis.
AB - Effective control of many diseases requires the accurate detection of infected
individuals. Confidently ascertaining whether an individual is infected can be
challenging when diagnostic tests are imperfect and when some individuals go for
long periods of time without being observed or sampled. Here, we use a multi
event capture-recapture approach to model imperfect observations of true
epidemiological states. We describe a method for interpreting potentially
disparate results from individuals sampled multiple times over an extended
period, using empirical data from a wild badger population naturally infected
with Mycobacterium bovis as an example. We examine the effect of sex, capture
history and current and historical diagnostic test results on the probability of
being truly infected, given any combination of diagnostic test results. In doing
so, we move diagnosis away from the traditional binary classification of
apparently infected versus uninfected to a probability-based interpretation which
is updated each time an individual is re-sampled. Our findings identified
temporal variation in infection status and suggest that capture probability is
influenced by year, season and infection status. This novel approach to combining
ecological and epidemiological data may aid disease management decision-making by
providing a framework for the integration of multiple diagnostic test data with
other information.
PMID- 28424455
TI - Flow virometry analysis of envelope glycoprotein conformations on individual HIV
virions.
AB - HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a
correct trimeric conformation, Env mediates virus-cell binding and fusion.
Malfunctioning of this machinery renders virions incapable of infecting cells.
Each HIV-1 virion carries 10-14 Envs, and therefore a defective Env may not
necessarily render a HIV virion non-infectious, since other Env on the same
virion may still be functional. Alternatively, it is possible that on a given
virion either all the spikes are defective or all are functional. Here, we
investigate Env conformations on individual virions using our new nanotechnology,
"flow virometry", and a panel of antibodies that discriminate between various Env
conformations. We found that the majority of HIV-1 virions carry either only
trimeric ("functional") or only defective spikes. The relatively small
subfraction of virions that carry both functional and nonfunctional Envs
contributes little to HIV infection of human lymphoid tissue ex vivo. The
observation that the majority of virions exclusively express either functional or
nonfunctional forms of Env has important implications for understanding the role
of neutralizing and non-neutralizing antibodies in the immune control of HIV
infection as well as for the development of effective prophylactic strategies.
PMID- 28424456
TI - Paraquat poisoning induced pulmonary epithelial mesenchymal transition through
Notch1 pathway.
AB - Progressive pulmonary fibrosis is the most characteristic feature of subacute PQ
poisoning. Epithelial-to-mesenchymal transition (EMT) is reported to be involved
in the pulmonary fibrosis after PQ exposure. Recent evidence suggested Notch
signaling is required for EMT. In this study, we investigated whether Notch1 and
TGF-beta1/Smad3 signaling was involved in EMT caused by PQ. It is demonstrated
that A549 cells underwent EMT after treated with PQ at dose of 300 MUmol/L for 6
days, charactered by increasing expression of mesenchymal marker alpha-SMA and
decreasing expression of epithelial marker E-cadherin. We found that there was an
apparent increased expression of Notch1 and jagged-1 in PQ induced EMT process.
EMT could be enhanced by Jagged-1 ligand of Notch1, and be blocked by DAPT, a
gamma-secretase inhibitor. Our data also showed that the expression of TGF
beta1/Smad3 increased after Notch1 is elevated in EMT caused by PQ. Jagged-1
significantly induced SMA expression, and this induction was completely inhibited
by SB431542 in A549 cells. In conclusion, we demonstrated that Notch1 pathway was
important in EMT induced by PQ, and TGF-beta1/Smad3 signaling partly plays a role
as the downstream of Notch1.
PMID- 28424457
TI - Vertex coloring of graphs via phase dynamics of coupled oscillatory networks.
AB - While Boolean logic has been the backbone of digital information processing,
there exist classes of computationally hard problems wherein this paradigm is
fundamentally inefficient. Vertex coloring of graphs, belonging to the class of
combinatorial optimization, represents one such problem. It is well studied for
its applications in data sciences, life sciences, social sciences and technology,
and hence, motivates alternate, more efficient non-Boolean pathways towards its
solution. Here we demonstrate a coupled relaxation oscillator based dynamical
system that exploits insulator-metal transition in Vanadium Dioxide (VO2) to
efficiently solve vertex coloring of graphs. Pairwise coupled VO2 oscillator
circuits have been analyzed before for basic computing operations, but using
complex networks of VO2 oscillators, or any other oscillators, for more complex
tasks have been challenging in theory as well as in experiments. The proposed VO2
oscillator network harnesses the natural analogue between optimization problems
and energy minimization processes in highly parallel, interconnected dynamical
systems to approximate optimal coloring of graphs. We further indicate a
fundamental connection between spectral properties of linear dynamical systems
and spectral algorithms for graph coloring. Our work not only elucidates a
physics-based computing approach but also presents tantalizing opportunities for
building customized analog co-processors for solving hard problems efficiently.
PMID- 28424458
TI - Light penetration-coupled photoisomerization modeling for photodeformation of
diarylethene single crystal: upscaling isomerization to macroscopic deformation.
AB - Diarylethene is one of the photo-responsive materials that show rapid and
reversible changes in their color/electrochemical properties and macroscopic
deformations in the crystalline phase by light irradiation. Photoisomerization is
the main cause of the photo reactivity of diarylethene, and we established a
statistical model based on the density matrix formalism, which predicts
quantitative isomerization progress as a population term. The model reflects
photo-switching properties of the target molecule, which were characterized by
first principle calculations, and external stimulus factors (light irradiation
conditions and temperature). By merging light penetration physics with the model,
we derived light penetration depth dependent isomerization progress to
theoretically investigate photodeformation of single crystal. The model well
reproduced in-plane shear deformation under ultraviolet light irradiation which
would provide guideline for photoactuator design. In addition, the statistical
model addressed crucial findings (primary stimuli and molecular design parameter
for increasing the isomerization rate, external stimuli enhancing fluorescence
performance) itself.
PMID- 28424459
TI - Development and outcomes of a primary care-based sleep assessment service in
Canterbury, New Zealand.
AB - : Prior to 2007, increasing demand for sleep services, plus inability to
adequately triage severity, led to long delays in sleep assessment and accessing
continuous positive airway pressure. We established a community sleep assessment
service carried out by trained general practices using a standardised tool and
overnight oximetry. All cases were discussed at a multi-disciplinary meeting,
with four outcomes: severe obstructive sleep apnoea treated with continuous
positive airway pressure; investigation with more complex studies; sleep
physician appointment; no or non-severe sleep disorder for general practitioner
management. Assessment numbers increased steadily (~400 in 2007 vs. 1400 in
2015). Median time from referral to assessment and multi-disciplinary meeting was
28 and 48 days, respectively. After the first multi-disciplinary meeting, 23% of
cases were assessed as having severe obstructive sleep apnoea. More complex
studies (mostly flow based) were required in 49% of patients, identifying severe
obstructive sleep apnoea in a further 13%. Thirty-seven percent of patients had
obstructive sleep apnoea severe enough to qualify for funded treatment. Forty
eight percent of patients received a definitive answer from the first multi
disciplinary meeting. Median time from referral to continuous positive airway
pressure for 'at risk' patients with severe obstructive sleep apnoea, e.g.,
commercial drivers, was 49 days, while patients with severe obstructive sleep
apnoea but not 'at risk' waited 261 days for continuous positive airway pressure.
Ten percent of patients required polysomnography, and 4% saw a sleep specialist.
In conclusion, establishment of a community sleep assessment service and sleep
multi-disciplinary meeting led to significantly more assessments, with short
waiting times for treatment, especially in high-risk patients with severe
obstructive sleep apnoea. Most patients can be assessed without more complex
studies or face-to-face review by a sleep specialist. SLEEP DISORDERS: MORE
ASSESSMENTS, SHORTER WAITS WITH COMMUNITY SLEEP SERVICE: A community-based
service for common sleep disorders can provide rapid and easily accessed sleep
assessment and treatment. A team led by Michael Hlavac and Michael Epton from
Christchurch Hospital describe the creation of a sleep assessment service within
the Canterbury district of New Zealand, in which initial assessments are
conducted throughout the community by general practice teams under guidance and
advice from sleep specialists at the region's largest hospital. Before the
service, there were around 300 sleep assessments per year in all of Canterbury, a
region with a population of around 510,000. Now, that number has more than
tripled, with shorter waiting times for treatment, especially for people with
severe sleep apnoea. The authors conclude that most patients can be assessed for
a suspected sleep disorder without needing to visit a hospital's sleep unit.
PMID- 28424460
TI - Generation of heritable germline mutations in the jewel wasp Nasonia vitripennis
using CRISPR/Cas9.
AB - The revolutionary RNA-guided endonuclease CRISPR/Cas9 system has proven to be a
powerful tool for gene editing in a plethora of organisms. Here, utilizing this
system we developed an efficient protocol for the generation of heritable
germline mutations in the parasitoid jewel wasp, Nasonia vitripennis, a rising
insect model organism for the study of evolution, development of axis pattern
formation, venom production, haplo-diploid sex determination, and host-symbiont
interactions. To establish CRISPR-directed gene editing in N. vitripennis, we
targeted a conserved eye pigmentation gene cinnabar, generating several
independent heritable germline mutations in this gene. Briefly, to generate these
mutants, we developed a protocol to efficiently collect N. vitripennis eggs from
a parasitized flesh fly pupa, Sarcophaga bullata, inject these eggs with
Cas9/guide RNA mixtures, and transfer injected eggs back into the host to
continue development. We also describe a flow for screening mutants and
establishing stable mutant strains through genetic crosses. Overall, our results
demonstrate that the CRISPR/Cas9 system is a powerful tool for genome
manipulation in N. vitripennis, with strong potential for expansion to target
critical genes, thus allowing for the investigation of several important
biological phenomena in this organism.
PMID- 28424461
TI - A lack of coordination between sister-chromatids segregation and cytokinesis in
the oocytes of B6.YTIR (XY) sex-reversed female mice.
AB - The B6.YTIR (XY) mouse develops bilateral ovaries despite the expression of the
testis-determining gene Sry during gonadal differentiation. We reported that the
oocytes of the XY female are defective in their cytoplasm, resulting in a failure
in the second meiotic division after activation or fertilization in vitro.
However, the mechanism of meiotic failure or the cause of infertility remained to
be clarified. In the present study, we obtained mature oocytes from XY females by
superovulation and confirmed that these oocytes also fail in zygotic development.
By using confocal microscopy 3D-analysis, we demonstrated that meiotic spindles
were properly positioned and oriented in the MII-oocytes from XY females. After
parthenogenic activation, fewer oocytes from XY females extruded the second polar
body, and in those oocytes, sister-chromatids were often separated but neither
set entered the second polar body. ARP2, F-actin, and ORC4, known to play roles
in asymmetric meiotic division, were initially localized along the ooplasmic
membrane and concentrated over the MII-spindle but lost their cortical polarity
after activation while the sister-chromatids moved away from the oolemma in the
oocytes from XY females. Our results indicate that the second polar body
extrusion is uncoupled from the sister-chromatids separation in the oocytes from
XY female mouse.
PMID- 28424462
TI - Dietary behaviour of man-eating lions as revealed by dental microwear textures.
AB - Lions (Panthera leo) feed on diverse prey species, a range that is broadened by
their cooperative hunting. Although humans are not typical prey, habitual man
eating by lions is well documented. Fathoming the motivations of the Tsavo and
Mfuwe man-eaters (killed in 1898 in Kenya and 1991 in Zambia, respectively) may
be elusive, but we can clarify aspects of their behaviour using dental microwear
texture analysis. Specifically, we analysed the surface textures of lion teeth to
assess whether these notorious man-eating lions scavenged carcasses during their
depredations. Compared to wild-caught lions elsewhere in Africa and other large
feliforms, including cheetahs and hyenas, dental microwear textures of the man
eaters do not suggest extreme durophagy (e.g. bone processing) shortly before
death. Dental injuries to two of the three man-eaters examined may have induced
shifts in feeding onto softer foods. Further, prompt carcass reclamation by
humans likely limited the man-eaters' access to bones. Man-eating was likely a
viable alternative to hunting and/or scavenging ungulates due to dental disease
and/or limited prey availability.
PMID- 28424463
TI - Luciferase-Specific Coelenterazine Analogues for Optical Contamination-Free
Bioassays.
AB - Spectral overlaps among the multiple optical readouts commonly cause optical
contamination in fluorescence and bioluminescence. To tackle this issue, we
created five-different lineages of coelenterazine (CTZ) analogues designed to
selectively illuminate a specific luciferase with unique luciferase selectivity.
In the attempt, we found that CTZ analogues with ethynyl or styryl groups display
dramatically biased bioluminescence to specific luciferases and pHs by modifying
the functional groups at the C-2 and C-6 positions of the imidazopyradinone
backbone of CTZ. The optical contamination-free feature was exemplified with the
luciferase-specific CTZ analogues, which illuminated anti-estrogenic and
rapamycin activities in a mixture of optical probes. This unique bioluminescence
platform has great potential for specific and high throughput imaging of multiple
optical readouts in bioassays without optical contamination.
PMID- 28424464
TI - [18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo
imaging in a sodium iodide symporter-expressing tumor model.
AB - Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in
vivo cancer cell tracking in spontaneously metastasizing tumor models still poses
a challenge requiring highest sensitivity and excellent contrast. The goal of
this study was to evaluate if the recently introduced PET radiotracer
[18F]tetrafluoroborate ([18F]BF4-) is useful for sensitive and specific
metastasis detection in an orthotopic xenograft breast cancer model expressing
the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was
complemented by ex vivo fluorescence microscopy and gamma-counting of harvested
tissues. Radionuclide imaging with [18F]BF4- (PET/CT) was compared to the
conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4-
was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster
and more complete clearance from circulation. [18F]BF4--PET was also highly
specific as in all detected tissues cancer cell presence was confirmed
microscopically. Undetected comparable tissues were similarly found to be free of
metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET
failed due to low standard uptake values and low contrast caused by adjacent
metabolically active organs in this model. [18F]BF4--PET combined with NIS
expressing disease models is particularly useful whenever preclinical in vivo
cell tracking is of interest.
PMID- 28424465
TI - Predicting the potential distribution in China of Euwallacea fornicates
(Eichhoff) under current and future climate conditions.
AB - Euwallacea fornicatus (Eichhoff) is an important forest pest that has caused
serious damage in America and Vietnam. In 2014, it attacked forests of Acer
trialatum in the Yunnan province of China, creating concern in China's Forestry
Bureau. We used the CLIMEX model to predict and compare the potential
distribution for E. fornicates in China under current (1981-2010) and projected
climate conditions (2011-2040) using one scenario (RCP8.5) and one global climate
model (GCM), CSIRO-Mk3-6-0. Under both current and future climate conditions, the
model predicted E. fornicates to be mainly distributed in the south of China.
Comparing distributions under both climate conditions showed that the area of
potential distribution was projected to increase (mainly because of an increase
in favourable habitat) and shift to the north. Our results help clarify the
potential effect of climate change on the range of this forest pest and provide a
reference and guide to facilitate its control in China.
PMID- 28424466
TI - The role of the brown adipose tissue in beta3-adrenergic receptor activation
induced sleep, metabolic and feeding responses.
AB - Brown adipose tissue (BAT) is regulated by the sympathetic nervous system via
beta3-adrenergic receptors (beta3-AR). Here we tested the hypothesis that
pharmacological stimulation of beta3-ARs leads to increased sleep in mice and if
this change is BAT dependent. In wild-type (WT) animals, administration of CL
316,243, a selective beta3-AR agonist, induced significant increases in non-rapid
eye movement sleep (NREMS) lasting for 4-10 h. Simultaneously,
electroencephalographic slow-wave activity (SWA) was significantly decreased and
body temperature was increased with a delay of 5-6 h. In uncoupling protein 1
(UCP-1) knockout mice, the middle and highest doses of the beta3-AR agonist
increased sleep and suppressed SWA, however, these effects were significantly
attenuated and shorter-lasting as compared to WT animals. To determine if
somnogenic signals arising from BAT in response to beta3-AR stimulation are
mediated by the sensory afferents of BAT, we tested the effects of CL-316,243 in
mice with the chemical deafferentation of the intra-scapular BAT pads. Sleep
responses to CL-316,243 were attenuated by ~50% in intra-BAT capsaicin-treated
mice. Present findings indicate that the activation of BAT via beta3-AR leads to
increased sleep in mice and that this effect is dependent on the presence of UCP
1 protein and sleep responses require the intact sensory innervation of BAT.
PMID- 28424467
TI - The Time Course of Spatial Attention Shifts in Elementary Arithmetic.
AB - It has been proposed that elementary arithmetic induces spatial shifts of
attention. However, the timing of this arithmetic-space association remains
unknown. Here we investigate this issue with a target detection paradigm.
Detecting targets in the right visual field was faster than in the left visual
field when preceded by an addition operation, while detecting targets in the left
visual field was faster than in the right visual field when preceded by a
subtraction operation. The arithmetic-space association was found both at the end
of the arithmetic operation and during calculation. In contrast, the processing
of operators themselves did not induce spatial biases. Our results suggest that
the arithmetic-space association resides in the mental arithmetic operation
rather than in the individual numbers or the operators. Moreover, the temporal
course of this effect was different in addition and subtraction.
PMID- 28424468
TI - Effect of handgrip on coronary artery disease and myocardial infarction: a
Mendelian randomization study.
AB - Observational studies have reported an association of handgrip strength with risk
of cardiovascular disease. However, residual confounding and reverse causation
may have influenced these findings. A Mendelian randomization (MR) study was
conducted to examine whether handgrip is causally associated with cardiovascular
disease. Two single nucleotide polymorphisms (SNPs), rs3121278 and rs752045, were
used as the genetic instruments for handgrip. The effect of each SNP on coronary
artery disease/myocardial infarction (CAD/MI) was weighted by its effect on
handgrip strength, and estimates were pooled to provide a summary measure for the
effect of increased handgrip on risk of CAD/MI. MR analysis showed that higher
grip strength reduces risk for CAD/MI, with 1-kilogram increase in genetically
determined handgrip reduced odds of CAD by 6% (odds ratio (OR) = 0.94, 95%
confidence interval (CI) 0.91-0.99, P = 0.01), and reduced odds of MI by 7% (OR =
0.93, 95% CI 0.89-0.98, P = 0.003). No association of grip strength with type 2
diabetes, body mass index, LDL- and HDL-cholesterol, triglycerides and fasting
glucose was found. The inverse causal relationship between handgrip and the risk
of CAD or MI suggests that promoting physical activity and resistance training to
improve muscle strength may be important for cardiovascular health.
PMID- 28424469
TI - Thermally Triggered Mechanically Destructive Electronics Based On Electrospun
Poly(epsilon-caprolactone) Nanofibrous Polymer Films.
AB - Electronics, which functions for a designed time period and then degrades or
destructs, holds promise in medical implants, reconfigurable electronic devices
and/or temporary functional systems. Here we report a thermally triggered
mechanically destructive device, which is constructed with an ultra-thin
electronic components supported by an electrospun poly(epsilon-caprolactone)
nanofibrous polymer substrate. Upon heated over the melting temperature of the
polymer, the pores of the nanofibers collapse due to the nanofibers' microscopic
polymer chain relaxing and packing. As a result, the polymer substrate exhibits
approximately 97.5% area reduction. Ultra-thin electronic components can
therefore be destructed concurrently. Furthermore, by integrating a thin
resistive heater as the thermal trigger of Joule heating, the device is able to
on-demand destruct. The experiment and analytical results illustrate the
essential aspects and theoretical understanding for the thermally triggered
mechanical destructive devices. The strategy suggests a viable route for
designing destructive electronics.
PMID- 28424470
TI - Atom size electron vortex beams with selectable orbital angular momentum.
AB - The decreasing size of modern functional magnetic materials and devices cause a
steadily increasing demand for high resolution quantitative magnetic
characterization. Transmission electron microscopy (TEM) based measurements of
the electron energy-loss magnetic chiral dichroism (EMCD) may serve as the needed
experimental tool. To this end, we present a reliable and robust electron-optical
setup that generates and controls user-selectable single state electron vortex
beams with defined orbital angular momenta. Our set-up is based on a standard
high-resolution scanning TEM with probe aberration corrector, to which we added a
vortex generating fork aperture and a miniaturized aperture for vortex selection.
We demonstrate that atom size probes can be formed from these electron vortices
and that they can be used for atomic resolution structural and spectroscopic
imaging - both of which are prerequisites for future atomic EMCD investigations.
PMID- 28424471
TI - Human Luteinizing Hormone and Chorionic Gonadotropin Display Biased Agonism at
the LH and LH/CG Receptors.
AB - Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) have been
considered biologically equivalent because of their structural similarities and
their binding to the same receptor; the LH/CGR. However, accumulating evidence
suggest that LH/CGR differentially responds to the two hormones triggering
differential intracellular signaling and steroidogenesis. The mechanistic basis
of such differential responses remains mostly unknown. Here, we compared the
abilities of recombinant rhLH and rhCG to elicit cAMP, beta-arrestin 2
activation, and steroidogenesis in HEK293 cells and mouse Leydig tumor cells
(mLTC-1). For this, BRET and FRET technologies were used allowing quantitative
analyses of hormone activities in real-time and in living cells. Our data
indicate that rhLH and rhCG differentially promote cell responses mediated by
LH/CGR revealing interesting divergences in their potencies, efficacies and
kinetics: rhCG was more potent than rhLH in both HEK293 and mLTC-1 cells.
Interestingly, partial effects of rhLH were found on beta-arrestin recruitment
and on progesterone production compared to rhCG. Such a link was further
supported by knockdown experiments. These pharmacological differences demonstrate
that rhLH and rhCG act as natural biased agonists. The discovery of novel
mechanisms associated with gonadotropin-specific action may ultimately help
improve and personalize assisted reproduction technologies.
PMID- 28424472
TI - Temperature-dependent folding allows stable dimerization of secretory and virus
associated E proteins of Dengue and Zika viruses in mammalian cells.
AB - Dengue and Zika are two of the most important human viral pathogens worldwide. In
both cases, the envelope glycoprotein E is the main target of the antibody
response. Recently, new complex quaternary epitopes were identified which are the
consequence of the arrangement of the antiparallel E dimers on the viral surface.
Such epitopes can be exploited to develop more efficient cross-neutralizing
vaccines. Here we describe a successful covalent stabilization of E dimers from
Dengue and Zika viruses in mammalian cells. Folding and dimerization of secretory
E was found to be strongly dependent on temperature but independent of PrM co
expression. In addition, we found that, due to the close relationship between
flaviviruses, Dengue and Zika viruses E proteins can form heterodimers and
assemble into mosaic viral particles. Finally, we present new virus-free
analytical platforms to study and screen antibody responses against Dengue and
Zika, which allow for differentiation of epitopes restricted to specific domains,
dimers and higher order arrangements of E.
PMID- 28424473
TI - Highly gate-tuneable Rashba spin-orbit interaction in a gate-all-around InAs
nanowire metal-oxide-semiconductor field-effect transistor.
AB - III-V semiconductors have been intensively studied with the goal of realizing
metal-oxide-semiconductor field-effect transistors (MOSFETs) with high mobility,
a high on-off ratio, and low power consumption as next-generation transistors
designed to replace current Si technology. Of these semiconductors, a narrow band
gap semiconductor InAs has strong Rashba spin-orbit interaction, thus making it
advantageous in terms of both high field-effect transistor (FET) performance and
efficient spin control. Here we report a high-performance InAs nanowire MOSFET
with a gate-all-around (GAA) structure, where we simultaneously control the spin
precession using the Rashba interaction. Our FET has a high on-off ratio
(104~106) and a high field-effect mobility (1200 cm2/Vs) and both values are
comparable to those of previously reported nanowire FETs. Simultaneously, GAA
geometry combined with high- kappa dielectric enables the creation of a large and
uniform coaxial electric field (>107 V/m), thereby achieving highly controllable
Rashba coupling (1 * 10-11 eVm within a gate-voltage swing of 1 V), i.e. an
operation voltage one order of magnitude smaller than those of back-gated
nanowire MOSFETs. Our demonstration of high FET performance and spin
controllability offers a new way of realizing low-power consumption nanoscale
spin MOSFETs.
PMID- 28424474
TI - Molecular epidemiology and azole resistance mechanism study of Candida
guilliermondii from a Chinese surveillance system.
AB - We studied the molecular epidemiology and mechanism of azole resistance of 164 C.
guilliermondii isolates from a nationwide multi-center surveillance program. The
isolates were identified by ITS gene sequencing, and the in vitro susceptibility
to fluconazole and voriconazole was determined by broth microdilution method. The
14-alpha-demethylase gene ERG11 was amplified and sequenced, and microsatellite
analysis was performed to study the genetic relatedness of the isolates. Amongst
the 164 C. guilliermondii isolates, 15 (9.1%) and 17 (10.4%) isolates were
assigned to be non-wild type (non-WT) to fluconazole and voriconazole,
respectively. Sixteen sequence types (STs) were detected by comparing the amino
acid sequence polymorphisms of the ERG11 gene. Fifteen isolates of STs 9, 10, 12,
13, 14, 15 and 16, were all assigned to be non-WT to fluconazole and
voriconazole. By microsatellite analysis, 40 different genotypes were identified.
Thirty-seven isolates from one hospital (Z1) shared the same ERG11 sequence type
(ST 2), microsatellite genotype (PU40) and drug resistance pattern. In
conclusion, this is the first molecular epidemiology study of C. guilliermondii
in China. The rate of non-WT isolates to azoles was high and the accurate
contribution of ERG11 gene mutations to azole resistance need be confirmed by
further studies.
PMID- 28424475
TI - Achieving unlimited recording length in interference lithography via broad-beam
scanning exposure with self-referencing alignment.
AB - Large-area holographic gratings are of great importance in diverse fields
including long-range interference metrology, high-resolution astronomical
telescopes, and chirped-pulse-amplification systems. However, in conventional
interference lithography, the recording length is limited by the aperture of the
collimating lenses. Here we propose broad-beam scanning exposure which employs
the latent grating generated continuously during scanning for real-time dynamic
fringe locking and thus achieves unlimited recording length. This method is
experimentally proved to make high-quality gratings, and is expected to be a new
type of interference lithography.
PMID- 28424477
TI - Warming impact on herbivore population composition affects top-down control by
predators.
AB - Understanding warming impact on herbivores facilitates predicting plant/crop
dynamics in natural/agricultural systems. However, it remains unclear how warming
will affect herbivore population size and population composition, consequently
altering herbivore colonization in a tri-trophic system (plant-herbivore-predator
or crop-pest-biocontrol agent). We studied a soybean-aphid-lady beetle system, by
conducting (1) a laboratory warming experiment to examine warming impact (+2
degrees C or +4 degrees C) on the aphid population size and composition (alate
proportion), and (2) a field colonization experiment to examine whether the
warming-induced effect subsequently interacts with predators (lady beetles) in
affecting aphid colonization. The results showed that warming affected the
initial aphid population composition (reduced alate proportion) but not
population size; this warming-induced effect strengthened the top-down control by
lady beetles and slowing aphid colonization. In other words, biocontrol on crop
pests by predators could improve under 2-4 degrees C warming. Furthermore, aphid
colonization was affected by an interaction between the alate proportion and
predator (lady beetle) presence. This study suggests that warming affects
herbivore population composition and likely mediates top-down control on
herbivore colonization by predators. This mechanism may be crucial but
underappreciated in climate change ecology because population composition (wing
form, sex ratio, age/body size structure) shifts in many species under
environmental change.
PMID- 28424476
TI - Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and
Misfolded Protein Cargo.
AB - The fidelity of synaptic transmission depends on the integrity of the protein
machinery at the synapse. Unfolded synaptic proteins undergo refolding or
degradation in order to maintain synaptic proteostasis and preserve synaptic
function, and buildup of unfolded/toxic proteins leads to neuronal dysfunction.
Many molecular chaperones contribute to proteostasis, but one in particular,
cysteine string protein (CSPalpha), is critical for proteostasis at the synapse.
In this study we report that exported vesicles from neurons contain CSPalpha.
Extracellular vesicles (EV's) have been implicated in a wide range of functions.
However, the functional significance of neural EV's remains to be established.
Here we demonstrate that co-expression of CSPalpha with the disease-associated
proteins, polyglutamine expanded protein 72Q huntingtinex degrees n1 or
superoxide dismutase-1 (SOD-1G93A) leads to the cellular export of both 72Q
huntingtinex degrees n1 and SOD-1G93A via EV's. In contrast, the inactive
CSPalphaHPD-AAA mutant does not facilitate elimination of misfolded proteins.
Furthermore, CSPalpha-mediated export of 72Q huntingtinex degrees n1 is reduced
by the polyphenol, resveratrol. Our results indicate that by assisting local
lysosome/proteasome processes, CSPalpha-mediated removal of toxic proteins via
EVs plays a central role in synaptic proteostasis and CSPalpha thus represents a
potential therapeutic target for neurodegenerative diseases.
PMID- 28424478
TI - The prevalence of thalassemia in mainland China: evidence from epidemiological
surveys.
AB - Comprehensive data regarding the epidemiology and prevalence of thalassemia in
mainland China are lacking. To assess the prevalence of thalassemia, we performed
a meta-analysis including 16 articles published from 1981 to 2015. The overall
prevalence of alpha-thalassemia, beta-thalassemia and alpha + beta-thalassemia
was 7.88%, 2.21% and 0.48%, respectively. Trends in thalassemia prevalence in
mainland China were not steady; a prevalence map based on a geographic
information system (GIS) showed that the geographic distribution of thalassemia
was highest in the south of China and decreased from south to north.
Additionally, the most common alpha- and beta-globin gene mutation was --SEA and
CD41/42, respectively. The current study provides valuable information regarding
epidemiology and intervention and supports the planning, implementation and
management of prevention programmes for public health.
PMID- 28424479
TI - Wnt-beta Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis
and Dysfunction of the External Anal Sphincter.
AB - Wnt-beta catenin is an important signaling pathway in the genesis of fibrosis in
many organ systems. Our goal was to examine the role of Wnt pathway in the
external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New
Zealand White female rabbits were subjected to surgical EAS myotomy and
administered local injections of either a Wnt antagonist (sFRP-2; daily for 7
days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured
for 15 weeks after which the animals were sacrificed. Anal canal was harvested
and processed for histochemical studies (Masson trichrome stain), molecular
markers of fibrosis (collagen and transforming growth factor-beta) and
immunostaining for beta catenin. Surgical myotomy of the EAS resulted in
significant impairment in anal canal pressure and EAS muscle L-T function.
Following myotomy, the EAS muscle was replaced with fibrous tissue.
Immunostaining revealed beta catenin activation and molecular studies revealed
1.5-2 fold increase in the levels of markers of fibrosis. Local injection of sFRP
2 attenuated the beta catenin activation and fibrosis. EAS muscle content and
function was significantly improved following sFRP-2 treatment. Our studies
suggest that upregulation of Wnt signaling is an important molecular mechanism of
injury related EAS muscle fibrosis and sphincter dysfunction.
PMID- 28424480
TI - Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex
III deficiency caused by a Bcs1l mutation.
AB - Mitochondrial disorders are among the most prevalent inborn errors of metabolism
but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate
ketogenic diets (KDs) have shown beneficial effects in mouse models of
mitochondrial myopathies, with induction of mitochondrial biogenesis as the
suggested main mechanism. We fed KD to mice with respiratory chain complex III
(CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII
assembly factor. The mutant mice became persistently ketotic and tolerated the KD
for up to 11 weeks. Liver disease progression was attenuated by KD as shown by
delayed fibrosis, reduced cell death, inhibition of hepatic progenitor cell
response and stellate cell activation, and normalization of liver enzyme
activities. Despite no clear signs of increased mitochondrial biogenesis in the
liver, CIII assembly and activity were improved and mitochondrial morphology in
hepatocytes normalized. Induction of hepatic glutathione transferase genes and
elevated total glutathione level were normalized by KD. Histological findings and
transcriptome changes indicated modulation of liver macrophage populations by the
mutation and the diet. These results reveal a striking beneficial hepatic
response to KD in mice with mitochondrial hepatopathy and warrant further
investigations of dietary modification in the management of these conditions in
patients.
PMID- 28424481
TI - The first genome-wide association study identifying new susceptibility loci for
obstetric antiphospholipid syndrome.
AB - Antiphospholipid syndrome (APS) is the most important treatable cause of
recurrent pregnancy loss. The live birth rate is limited to only 70-80% in
patients with APS undergoing established anticoagulant therapy. Lupus
anticoagulant (LA), but not anticardiolipin antibody (aCL), was found to predict
adverse pregnancy outcome. Recent genome-wide association studies (GWAS) of APS
focusing on aCL have shown that several molecules may be involved. This is the
first GWAS for obstetric APS focusing on LA. A GWAS was performed to compare 115
Japanese patients with obstetric APS, diagnosed according to criteria of the
International Congress on APS, and 419 healthy individuals. Allele or genotype
frequencies were compared in a total of 426 344 single-nucleotide polymorphisms
(SNPs). Imputation analyses were also performed for the candidate regions
detected by the GWAS. One SNP (rs2288493) located on the 3'-UTR of TSHR showed an
experiment-wide significant APS association (P=7.85E-08, OR=6.18) under a
recessive model after Bonferroni correction considering the number of analyzed
SNPs. Another SNP (rs79154414) located around the C1D showed a genome-wide
significant APS association (P=4.84E-08, OR=6.20) under an allelic model after
applying the SNP imputation. Our findings demonstrate that a specific genotype of
TSHR and C1D genes can be a risk factor for obstetric APS.
PMID- 28424482
TI - Logistic Bayesian LASSO for genetic association analysis of data from complex
sampling designs.
AB - Detecting gene-environment interactions with rare variants is critical in
dissecting the etiology of common diseases. Interactions with rare haplotype
variants (rHTVs) are of particular interest. At the same time, complex sampling
designs, such as stratified random sampling, are becoming increasingly popular
for designing case-control studies, especially for recruiting controls. The US
Kidney Cancer Study (KCS) is an example, wherein all available cases were
included while the controls at each site were randomly selected from the
population by frequency matching with cases based on age, sex and race. There is
currently no rHTV association method that can account for such a complex sampling
design. To fill this gap, we consider logistic Bayesian LASSO (LBL), an existing
rHTV approach for case-control data, and show that its model can easily
accommodate the complex sampling design. We study two extensions that include
stratifying variables either as main effects only or with additional modeling of
their interactions with haplotypes. We conduct extensive simulation studies to
compare the complex sampling methods with the original LBL methods. We find that,
when there is no interaction between haplotype and stratifying variables, both
extensions perform well while the original LBL methods lead to inflated type I
error rates. However, when such an interaction exists, it is necessary to include
the interaction effect in the model to control the type I error rate. Finally, we
analyze the KCS data and find a significant interaction between (current) smoking
and a specific rHTV in the N-acetyltransferase 2 gene.
PMID- 28424483
TI - Magnetic moment of inertia within the torque-torque correlation model.
AB - An essential property of magnetic devices is the relaxation rate in magnetic
switching which strongly depends on the energy dissipation. This is described by
the Landau-Lifshitz-Gilbert equation and the well known damping parameter, which
has been shown to be reproduced from quantum mechanical calculations. Recently
the importance of inertia phenomena have been discussed for magnetisation
dynamics. This magnetic counterpart to the well-known inertia of Newtonian
mechanics, represents a research field that so far has received only limited
attention. We present and elaborate here on a theoretical model for calculating
the magnetic moment of inertia based on the torque-torque correlation model.
Particularly, the method has been applied to bulk itinerant magnets and we show
that numerical values are comparable with recent experimental measurements. The
theoretical analysis shows that even though the moment of inertia and damping are
produced by the spin-orbit coupling, and the expression for them have common
features, they are caused by very different electronic structure mechanisms. We
propose ways to utilise this in order to tune the inertia experimentally, and to
find materials with significant inertia dynamics.
PMID- 28424484
TI - The tandem Agenet domain of fragile X mental retardation protein interacts with
FUS.
AB - The tandem Agenet domain (TAD) of fragile X mental retardation protein (FMRP)
protein is considered to be a member of the methyl-lysine-binding Tudor domain
"Royal family". Several groups have reported that the TAD binds with methylated
histones and plays a role in DNA damage responses. FMRP is a RNA-binding protein
predominantly resident in cytoplasm. Therefore, in this study, we identified
DDX5, FUS, EWSR1 and LSM14A as TAD-interacting proteins sensitive to F32L and/or
Y96L mutation by pull-down assays and mass spectrometry. We also showed that the
interaction is potentially mediated by RGG/RG motifs. Furthermore, when FMRP was
knocked-down, translocation of exogenously expressed wild-type FUS and disease
related mutant R514G was observed. This study may provide a novel insight into
FMRP involvement in the intracellular localization of FUS and pathology of FUS
related amyotrophic lateral sclerosis.
PMID- 28424485
TI - In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the
trigeminal ganglia.
AB - The ability to genetically manipulate trigeminal ganglion (TG) neurons would be
useful in the study of the craniofacial nervous system and latent
alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors
for gene delivery to the TG after intradermal whiskerpad delivery in mice. We
demonstrated that AAV vectors of serotypes 1, 7, 8, and 9 trafficked from the
whiskerpad into TG neurons and expressed transgenes within cell bodies and axons
of sensory neurons in all three branches of the TG. Gene expression was highest
with AAV1, and steadily increased over time up to day 28. Both constitutive and
neuronal-specific promoters were able to drive transgene expression in TG
neurons. Levels of vector genomes in the TG increased with input dose, and
multiple transgenes could be co-delivered to TG neurons by separate AAV vectors.
In conclusion, AAV1 vectors are suitable for gene delivery to TG sensory neurons
following intradermal whiskerpad injection.
PMID- 28424486
TI - Meta-analysis Reveals the Prognostic Value of Circulating Tumour Cells Detected
in the Peripheral Blood in Patients with Non-Metastatic Colorectal Cancer.
AB - Detecting circulating tumour cells (CTCs) is considered as effective and
minimally invasive technique to predict the prognosis of patients with metastatic
colorectal cancer (CRC), but its clinical validity is still conflicting in
patients without metastasis. We performed this meta-analysis to evaluate whether
detection of CTCs in the peripheral blood can be used as a prognostic marker for
patients with non-metastatic CRC. We performed a comprehensive search of the
EMBASE, PubMed, and Web of Science databases (up to September 2016). Meta
analyses were conducted using a random-effects model with the hazard ratio (HR)
and 95% confidence interval (95% CI) as the effect measures. Twenty studies
including 3,687 patients were eligible for inclusion. Overall analyses
demonstrated that the presence of CTCs was significantly associated with
aggressive disease progression (HR = 2.57, 95% CI = 1.64-4.02, P heterogeneity <
0.001, I 2 = 81.0%) and reduced disease survival (HR = 2.41, 95% CI = 1.66-3.51,
P heterogeneity = 0.002, I 2 = 59.7%). Subgroup analyses further supported the
prognostic effect of CTCs based on different subsets, including sampling time,
detection method and cancer type. Our findings suggest that detection of CTCs in
the peripheral blood has the clinical utility to indicate poor prognosis in
patients with non-metastatic CRC.
PMID- 28424487
TI - Power Flow in a Large-Core Multimode Fiber under External Perturbation and its
Applications.
AB - Large core optical multimode fiber provides benefits such as a large light
coupling tolerance, easy handling, and delivery of higher light power without
undesirable nonlinear effects. In this research, we exploit the effects of
external perturbation on the power flow within the large core fiber and present
two relevant applications, namely a perturbation sensor and a doughnut beam
tuner. Since conventional multimode fiber power flow model does not take into
consideration the perturbation effect, we modify the power flow model so that the
influence of time varying perturbation can be theoretically analyzed. Based on
our theory, we further conduct the numerical simulation and experiments on these
two applications. For the fiber vibration sensor, the proposed numerical model
shows that the sensor sensitivity depends on the intensity profile of the
launched beam and also the higher-order harmonics that were not reported
previously can become interferences to affect the signal. For the beam tuner
application, we prove both theoretically and experimentally that the doughnut
intensity profile at the fiber output can be tuned in real-time by applying
external perturbations to the fiber. We expect that the results can be useful to
further exploit the external perturbation on large core fiber in various
applications.
PMID- 28424488
TI - Improving superconductivity in BaFe2As2-based crystals by cobalt clustering and
electronic uniformity.
AB - Quantum materials such as antiferromagnets or superconductors are complex in that
chemical, electronic, and spin phenomena at atomic scales can manifest in their
collective properties. Although there are some clues for designing such
materials, they remain mainly unpredictable. In this work, we find that
enhancement of transition temperatures in BaFe2As2-based crystals are caused by
removing local-lattice strain and electronic-structure disorder by thermal
annealing. While annealing improves Neel-ordering temperature in BaFe2As2 crystal
(T N = 132 K to 136 K) by improving in-plane electronic defects and reducing
overall a-lattice parameter, it increases superconducting-ordering temperature in
optimally cobalt-doped BaFe2As2 crystal (T c = 23 to 25 K) by precipitating-out
the cobalt dopants and giving larger overall a-lattice parameter. While annealing
improves local chemical and electronic uniformity resulting in higher T N in the
parent, it promotes nanoscale phase separation in the superconductor resulting in
lower disparity and strong superconducting band gaps in the dominant crystal
regions, which lead to both higher overall T c and critical-current-density, J c
.
PMID- 28424489
TI - Porous Graphene Sponge Additives for Lithium Ion Batteries with Excellent Rate
Capability.
AB - Rate capability as well as power performance of lithium ion batteries (LiBs) is
becoming more and more important, especially as the application targets of LiBs
move from mobile devices to transportation, such as EVs and HEVs. In this
research, we report porous graphene sponge additives for both anode and cathode
materials for better rate performance. The charge capacity retention improved
from 56% to 77% at 6C and from 7% to 45% at 10C with 0.5 wt% added to the anode,
while the discharge capacity retention at the 6C rate improved from 43% to 76%
and the 10C rate discharge improved from 16% to 40% with the same amount of MG
added to the cathode. The cyclability at high rate was also improved with the MG
additive. Moreover, preparation of the MG was facile, cost-effective, and
compatible with commercially available active materials. These results
demonstrate the suitability of MG for use with LiB additives to ensure better
rate capability and high rate cyclability.
PMID- 28424490
TI - Direct recognition of LPS drive TLR4 expressing CD8+ T cell activation in
patients with rheumatoid arthritis.
AB - Aberrant immune responses characterize autoimmune disorders like Rheumatoid
Arthritis (RA) wherein lymphocytes are recognized as key players. Role of CD8+ T
cells in RA has been less defined however we found that these cells are activated
in RA patients with increased expression of cytolytic granules and inflammatory
mediators thereby modulating immune responses contributing to disease severity.
Though unconventional expression of different Toll Like Receptors (TLRs) on CD8+
T cells has been proposed but their expression and role in T cell activation and
differentiation in RA still remains obscure. Herein we report, for the first
time, an increased expression of TLR4 on peripheral CD8+ T cells of RA patients
and its role in skewing CD8+ T cells towards activated and inflammatory phenotype
thereby playing a significant role in pathogenesis and progression of RA. We
found that the surface expression of TLR4 on CD8+ T cells directly correlates
with disease severity. Moreover, these CD8+ T cells respond to the TLR4 ligand
LPS and express robust amounts of cytotolytic and inflammatory molecules
including TNFalpha and IFNgamma. Our study hence identifies an important role for
CD8+ T cells in orchestrating RA through TLR4 mediated activation and
differentiation.
PMID- 28424491
TI - Understanding the ion-induced elongation of silver nanoparticles embedded in
silica.
AB - In this work we have studied the elongation of silver nanoparticles irradiated
with 40 MeV Bromine ions by means of in situ optical measurements, transmission
electron microscopy and molecular dynamics simulations. The localized surface
plasmon resonance of silver nanoparticles has a strong dependence on the particle
shape and size, which allowed us to obtain the geometrical parameters with
remarkable accuracy by means of a fit of the optical spectra. Optical results
have been compared with transmission electron microscopy images and molecular
dynamics simulations and the agreement is excellent in both cases. An important
advantage of in situ measurements is that they yield an extremely detailed
information of the full elongation kinetics. Final nanoparticle elongation
depends on a complex competition between single-ion deformation, Ostwald ripening
and dissolution. Building and validating theoretical models with the data
reported in this work should be easier than with the information previously
available, due to the unprecedented level of kinetic details obtained from the in
situ measurements.
PMID- 28424492
TI - TestSTORM: Versatile simulator software for multimodal super-resolution
localization fluorescence microscopy.
AB - Optimization of sample, imaging and data processing parameters is an essential
task in localization based super-resolution microscopy, where the final image
quality strongly depends on the imaging of single isolated fluorescent molecules.
A computational solution that uses a simulator software for the generation of
test data stacks was proposed, developed and tested. The implemented advanced
physical models such as scalar and vector based point spread functions,
polarization sensitive detection, drift, spectral crosstalk, structured
background etc., made the simulation results more realistic and helped us
interpret the final super-resolved images and distinguish between real structures
and imaging artefacts.
PMID- 28424493
TI - Regulation of intraocular pressure by microRNA cluster miR-143/145.
AB - Glaucoma is a major cause of irreversible blindness worldwide. Elevated
intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion
cell death, is the primary risk factor for blindness in glaucoma patients. IOP is
controlled by the balance between aqueous humor secretion from the ciliary body
(CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs)
regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143
and miR-145 expression is enriched in the smooth muscle and trabecular meshwork
in the eye. Targeted deletion of miR-143/145 in mice results in significantly
reduced IOP, consistent with an ~2-fold increase in outflow facilities. However,
aqueous humor production in the same mice appears to be normal based on a
microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145
regulates actin dynamics and the contractility of TM cells, consistent with its
regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well
as myosin light chain kinase (MLCK) in these cells. Our data establish miR
143/145 as important regulators of IOP, which may have important therapeutic
implications in glaucoma.
PMID- 28424494
TI - Predictable phenotypic, but not karyotypic, evolution of populations with
contrasting initial history.
AB - The relative impact of selection, chance and history will determine the
predictability of evolution. There is a lack of empirical research on this
subject, particularly in sexual organisms. Here we use experimental evolution to
test the predictability of evolution. We analyse the real-time evolution of
Drosophila subobscura populations derived from contrasting European latitudes
placed in a novel laboratory environment. Each natural population was sampled
twice within a three-year interval. We study evolutionary responses at both
phenotypic (life-history, morphological and physiological traits) and karyotypic
levels for around 30 generations of laboratory culture. Our results show (1)
repeatable historical effects between years in the initial state, at both
phenotypic and karyotypic levels; (2) predictable phenotypic evolution with
general convergence except for body size; and (3) unpredictable karyotypic
evolution. We conclude that the predictability of evolution is contingent on the
trait and level of organization, highlighting the importance of studying multiple
biological levels with respect to evolutionary patterns.
PMID- 28424495
TI - Significance of genetic polymorphisms in long non-coding RNA AC079767.4 in
tuberculosis susceptibility and clinical phenotype in Western Chinese Han
population.
AB - Recent studies have implicated long non-coding RNA, AC079767.4, as a highly
susceptible gene in tuberculosis. The aim of the study was to preliminarily
explore the possible association of single nucleotide polymorphisms (SNPs) in
AC079767.4 gene with clinical phenotypes and TB susceptibility in Western Chinese
Han population. The improved multiplex ligation detection reaction (iMLDR) method
was employed to genotype 4 SNPs in AC079767.4 in 554 tuberculosis patients and
561 healthy individuals. In subgroup analysis, only the C allele for rs12477677
was associated with the decreased susceptibility to pulmonary TB with a p-value
of 0.026, but p-value was 0.103 after Bonferroni correction. In total samples,
haplotype [ACAC], representing four AC079767.4 variants, was found to slightly
decrease TB risk (p = 0.045). Furthermore, patients with the CC genotype of
rs12477677 were correlated with fewer occurrences of fever (p = 0.016), while
patients carrying the T allele were associated with lower levels of ESR in the
dominant model of rs1055229 (p = 0.021). For the first time, we reported the
potential susceptibility and clinical traits of tuberculosis with lncRNA variants
in the Western Han Chinese population. Our data indicate AC079767.4 polymorphisms
may potentially act as novel biomarkers for tuberculosis diagnostic and
therapeutic purposes.
PMID- 28424496
TI - The Chemical Characterization of Nigerian Propolis samples and Their Activity
Against Trypanosoma brucei.
AB - Profiling of extracts from twelve propolis samples collected from eight regions
in Nigeria was carried out using high performance liquid chromatography (LC)
coupled with evaporative light scattering (ELSD), ultraviolet detection (UV) and
mass spectrometry (MS), gas chromatography mass spectrometry (GC-MS) and nuclear
magnetic resonance spectroscopy (NMR). Principal component analysis (PCA) of the
processed LC-MS data demonstrated the varying chemical composition of the
samples. Most of the samples were active against Trypanosoma b. brucei with the
highest activity being in the samples from Southern Nigeria. The more active
samples were fractionated in order to isolate the component(s) responsible for
their activity using medium pressure liquid chromatography (MPLC). Three
xanthones, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, 1,3,7-trihydroxy
4,8-di-(3-methylbut-2-enyl)xanthone a previously undescribed xanthone and three
triterpenes: ambonic acid, mangiferonic acid and a mixture of alpha-amyrin with
mangiferonic acid (1:3) were isolated and characterised by NMR and LC-MS. These
compounds all displayed strong inhibitory activity against T.b. brucei but none
of them had higher activity than the crude extracts. Partial least squares (PLS)
modelling of the anti-trypanosomal activity of the sample extracts using the LC
MS data indicated that high activity in the extracts, as judged from LCMS2 data,
could be correlated to denticulatain isomers in the extracts.
PMID- 28424497
TI - The glycogen synthase kinase MoGsk1, regulated by Mps1 MAP kinase, is required
for fungal development and pathogenicity in Magnaporthe oryzae.
AB - Magnaporthe oryzae, the causal agent of blast disease, is one of the most
destructive plant pathogens, causing significant yield losses on staple crops
such as rice and wheat. The fungus infects plants with a specialized cell called
an appressorium, whose development is tightly regulated by MAPK signaling
pathways following the activation of upstream sensors in response to
environmental stimuli. Here, we show the expression of the Glycogen synthase
kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly
under the stressed conditions. Thus, MoGSK1 is functionally characterized in this
study. MoGsk1 is functionally homologues to the Saccharomyces cerevisiae GSK3
homolog MCK1. Gene replacement of MoGSK1 caused significant delay in mycelial
growth, complete loss of conidiation and inability to penetrate the host surface
by mycelia-formed appressorium-like structures, consequently resulting in loss of
pathogenicity. However, the developmental and pathogenic defects of Deltamogsk1
are recovered via the heterologous expression of Fusarium graminearum GSK3
homolog gene FGK3, whose coding products also shows the similar cytoplasmic
localization as MoGsk1 does in M. oryzae. By contrast, overexpression of MoGSK1
produced deformed appressoria in M. oryzae. In summary, our results suggest that
MoGsk1, as a highly conservative signal modulator, dictates growth, conidiation
and pathogenicity of M. oryzae.
PMID- 28424498
TI - Efficacy and safety of a newly developed polylactic acid microsphere as an
injectable bulking agent for penile augmentation: 18-months follow-up.
AB - Polylactic acid (PLA) fillers are widely used for cosmetic volume augmentation.
But, no study has evaluated the use of PLA filler in penile augmentation (PA No.
4). We evaluated the efficacy and safety of a newly developed PLA filler for PA
during a 18-month follow-up period. A total of 23 healthy adult men were
prospectively enrolled between June and November 2012. Penile girth was measured
at proximal-, mid- and distal-shaft at baseline, 3, 6, 12 and 18 months following
injection. Subjects' satisfaction was assessed with visual analogue scale (VAS).
Adverse events (AEs) were also reported. Mean injected volume was 20 ml. The
circumference of proximal-, mid-, and distal-shaft increased by a mean of 2.2+/
0.2, 2.7+/-1.0 and 2.7+/-1.0 cm at 3 months, respectively (each P<0.001). No
significant differences were noted in girth circumference between 3 and 18 months
post-injection (each P>0.05). VAS score increased from 51.6+/-14.7 at baseline to
64.8+/-19.3 and 74.3+/-14.6 at 3 and 6 months, respectively (each P<0.05). Six
cases of mild, transient treatment-emergent AEs were reported in 5 subjects.
Serious AEs were not reported. In conclusion, penile injection of a newly
developed PLA filler led to significant penile augmentative effects for up to 18
months and was well tolerated without serious AEs.
PMID- 28424499
TI - Tamsulosin for treatment of lower urinary tract symptoms in women: a systematic
review and meta-analysis.
AB - Tamsulosin has been used for the off-label treatment of lower urinary tract
symptoms (LUTS) in women. Over the past few years, several randomized controlled
trials (RCTs) have reported the clinical effectiveness and safety of tamsulosin
for LUTS in women. Therefore, the aim of the present study was to perform a meta
analysis to evaluate the safety and efficacy of tamsulosin in treating LUTS in
women, which may resolve some of the current controversies over use of the drug
and provide more reliable evidence for the use of tamsulosin. A literature review
was performed to identify all published RCTs of tamsulosin for the treatment of
LUTS in women. The search included the following databases: PUBMED, EMBASE, the
Cochrane Controlled Trail Register of Controlled Trials, Chinese Biomedical
Literature Database, China National Knowledge Infrastructure, Chinese Science and
Technique Journals Database (VIP) and Wanfang Database. A systematic review and
meta-analysis were conducted. Six RCTs studies involving 764 female participants
were included in the analysis. Four out of the six RCTs compared tamsulosin with
placebo, one RCT compared tamsulosin with prazosin and the other study compared
tamsulosin with tamsulosin combined with tolterodine. Two RCTs evaluated total
International Prostate Symptom Score (IPSS) and improved total IPSS compared with
the placebo (standardized mean difference=-4.08, 95% confidence interval=-5.93 to
-2.23, P<0.00001). IPSS (storage symptom score), IPSS (voiding symptom score) and
quality-of-life score also showed the similar effects. In addition, tamsulosin
improved the Overactive Bladder Questionnaire score when compared with placebo in
only one RCT. For urodynamic parameters, tamsulosin improved the average flow
rate and the post-void residual volume when compared with prazosin and
tolterodine combined with tamsulosin, respectively. Beyond that, the other
parameters showed no significant difference between the treatment and control
groups. On the basis of the present evidence, tamsulosin is an effective
treatment for the relief of LUTS in women when compared with placebo. However,
the safety of the tamsulosin remains unknown. Further, well-conducted trials that
examine long-term outcomes are required.
PMID- 28424500
TI - Percutaneous transluminal coronary angioplasty for acute myocardial infarction:
the impact on sexual function in men.
AB - The aim of this study was to evaluate changes in men's sexual function after
percutaneous transluminal coronary angioplasty (PTCA) treatment for acute
myocardial infarction (MI). Sixty men aged 18-70 years old were included in the
study. All patients had acute MI and underwent PTCA. They underwent two post PCTA
visits: 3 days and between 4 and 6 months after PTCA. During the first and second
visit a standard medical interview was carried out and sexual function data
collected using Changes in Sexual Functioning Questionnaire and International
Index of Erectile Function (IIEF-15). The results showed no statistical
differences in IIEF and CSQF scores before and after PTCA. However, when cutoff
points were used, a significant decrease in severe erectile dysfunction (ED)
prevalence according to IIEF (25.0% vs 16.7%; P=0.02) was observed. Based on the
results, we concluded that sexual function significantly improved in the subset
of men with severe ED who underwent PTCA as a treatment for acute MI, 4-6 months
after the procedure.
PMID- 28424501
TI - Translation and validation of the Greek version of the female sexual function
index questionnaire.
AB - The clinical evaluation of female sexual dysfunctions should be supplemented by
validated questionnaires; however, there is no specific instrument available in
Greek language. The study was designed to linguistically validate the Greek
version of Female Sexual Function Index (FSFI). Ninety-nine healthy women and
eighteen women with a sexual dysfunction were recruited through a survey and were
asked to voluntarily complete the FSFI questionnaire in Greek (FSFI-Gr) at
baseline and after 2 weeks. We assessed validity, internal consistency
reliability and test-retest reliability of the FSFI greek version. Subscales of
the FSFI showed good internal consistency reliability (Cronbach's=0.92, P<0.01).
Test-retest reliability median 14 days apart was excellent with intraclass
coefficient 0.91 (P<0.01). The FSFI-Gr discriminated between women with and
without sexual dysfunction with an optimal cutoff score 26 (sensitivity 71.4%,
specificity 92.2%). The Greek version of the FSFI is a reliable tool for the
assessment of female sexual dysfunction. The results show that it is comparable
to the outcome of studies in English-speaking countries.
PMID- 28424502
TI - Significance of serum endothelial cell specific molecule-1 (Endocan) level in
patients with erectile dysfunction: a pilot study.
AB - This study aimed to measure the serum endocan level of patients with erectile
dysfunction (ED) and to investigate the possible association between the
Endothelial-specific molecule-1 (Endocan) level and ED. Twenty healthy and sixty
four male patients included in the study were divided into four groups: severe ED
(19 patients), moderate ED (24 patients), mild ED (21 patients) and control group
(20 healthy men). The erectile function of all the patients was evaluated using
the International Index of Erectile Function-5 (IIEF-5) questionnaire. The body
mass index (BMI) of each participant was determined, together with levels of
fasting blood glucose, total testosterone, low- and high-density lipoprotein
cholesterol, triglyceride and endocan in serum samples. No significant difference
was found between the three ED groups and the control group in terms of the mean
age, BMI and the levels of cholesterol and fasting blood glucose (P>0.05). The
mean serum endocan level was found to 1.076+/-0.5, 0.674+/-0.40 and 0.671+/-0.3
ng ml-1 in the severe, moderate and mild ED groups, respectively. This indicated
that the highest value was obtained from the severe ED group, and the difference
between the severe ED group and the other groups was statistically significant.
In the control group, the serum endocan level was 0.73+/-0.46 ng ml-1, which was
significantly higher compared to the moderate and mild ED groups (P<0.05). The
significant difference between the control and ED groups in terms of the serum
endocan level can assist in the evaluation of endothelial pathologies in the
etiology ED.
PMID- 28424503
TI - Sexuality education in Japanese medical schools.
AB - The present study aimed to investigate current sexuality education in Japanese
medical schools and the impact of position title in the Japanese Society for
Sexual Medicine (JSSM). Questionnaires were mailed to urology departments in all
Japanese medical schools. The responses were evaluated according to four factors:
the number of lecture components, curriculum hours, degree of satisfaction with
the components and degree of satisfaction with the curriculum hours. We also
investigated differences in these four factors among three groups: Directors,
Council members and non-members of the JSSM. The medians of curriculum hours and
the number of the lecture components were 90.0 min and 7.0, respectively. The
curriculum hours of the Directors (140.0 min) were significantly longer than
those of the non-members (90.0 min; P<0.05). The number of lecture components
taught by Directors (9.5) was significantly higher than that of the Council (4.0;
P<0.01) and non-members (7.0; P<0.05). More than half of the faculties were not
satisfied with the lecture components and curriculum hours. This is the first
study on sexuality education in Japanese medical schools. It showed the
inadequacy of both curriculum hours and lecture components, and that the position
title of department chair affects sexuality education in medical schools.
PMID- 28424504
TI - Prevalence and factors associated with erectile dysfunction in patients with
chronic kidney disease on conservative treatment.
AB - Population with chronic kidney disease (CKD) has had many problems, and some of
these have arisen from sexual disorders. The present study intends to determine
the prevalence and the associated factors with erectile dysfunction (ED) among
patients with CKD on conservative treatment (CKDCT). This transversal study was
conducted from May 2013 to December 2015. The tools used were: medical records
and the International Index of Erectile Function. Data were analyzed by
univariate and multivariate logistic regression analysis. Among 245 patients that
have participated of this study, ED was present in 71.02% and it was severe in
36.73%. Age greater than 50 years, body mass index lower than 25, diabetes
mellitus, stages IV/V of CKD, cardiac conduction disturbances, benign prostatic
hyperplasia, smoking, alcohol use, albumin <3.5 g per 100 ml and creatinine
clearance between 15 and 29 ml min-1 per 1.73 m2 were associated with ED. Time
of CKD was the only variable associated with ED independent of the presence of
other factors. ED prevalence in patients with CKDCT is high and it is severe in
more than half of them. Several factors are associated with ED in this population
but the principal one is the time of CKD.
PMID- 28424505
TI - Usefulness of serum fetuin-A level as a marker of erectile dysfunction.
AB - This study aimed to evaluate the correlation between serum levels of fetuin-A and
the presence and severity of erectile dysfunction (ED) in Egyptian population.
The study was performed on 60 ED patients and 20 age-matched healthy controls. A
comprehensive medical history and complete physical examination were obtained and
performed in all participants. ED and its severity were assessed via
International Index of Erectile Function (IIEF-5). Doppler ultrasound, fasting
blood glucose level, complete lipid profile, serum total testosterone (TT) and
serum fetuin-A were performed. Our results revealed that there were no
statistically significant differences between the ED group and the controls
regarding body mass index, fetal bovine serum, cholesterol, low-density
lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG). However,
IIEF-5 and serum TT levels were significantly lower in ED patients than controls.
Regarding serum fetuin-A, our data demonstrated that ED patients had
significantly lower serum fetuin-A levels than controls. In addition, patients
with severe ED had lower fetuin-A levels than moderate and mild ED (P<0.001).
Serum fetuin-A levels are positively correlated with cholesterol, LDL, TG and
IIEF-5 and negatively correlated with HDL. In conclusion, serum fetuin-A level
could be a potentially useful and sensitive biomarker for ED diagnosis.
PMID- 28424506
TI - Long-term outcomes of AMS Spectra(r) penile prosthesis implantation and
satisfaction rates.
AB - The aim of this study was to evaluate the surgical implantation techniques of AMS
Spectra malleable penile prosthesis, its intraoperative and postoperative
complications, and the rates of patient and partner satisfaction. Forty-six
patients on whom AMS Spectra malleable penile prosthesis implantation was
performed between 2009 and 2014 were retrospectively examined. Any complications
seen intraoperatively and postoperatively were determined. International Index of
Erectile Function (IIEF)-5, total IIEF erectile function domain scores were
calculated preoperatively. IIEF-5, total IIEF erectile function domain and
Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were
calculated in the postoperative third, sixth and twelfth months. The mean age of
the patients was 63.6+/-7.28 (38-80) years. The mean erectile dysfunction period
was 4.29+/-2.51 years, and the mean follow-up period was 3.19+/-1.6 years. The
mean IIEF-5 score was 5.86+/-0.92 before surgery, and it was 22.5+/-0.62 at the
end of the follow-up. The mean total IIEF erectile function domain score was
6.02+/-1.09 before surgery, and it was 26.02+/-0.21 at the end of the follow-up.
The mean EDITS score was 71.06+/-3.16 at the end of the follow-up. The mean EDITS
score of the patients partners was 65.08+/-4.34 at the end of the follow-up. The
overall satisfaction rates were 96.2% for the patients and 84.6% for the
partners. As a result of this study, the AMS Spectra penile prosthesis
implantation is an effective, reliable and economic method. It can be used in the
treatment of erectile dysfunction in selected patient groups offering high
patient and partner satisfaction rates.
PMID- 28424507
TI - Heat Stress in Dairy Cattle Alters Lipid Composition of Milk.
AB - Heat stress, potentially affecting both the health of animals and the yield and
composition of milk, occurs frequently in tropical, sub-tropical and temperate
regions. A simulated acute heat stress experiment was conducted in controlled
climate chambers and milk samples collected before, during and after the heat
challenge. Milk lipid composition, surveyed using LC-MS, showed significant
changes in triacylglycerol (TAG) and polar lipid profiles. Heat stress
(temperature-humidity index up to 84) was associated with a reduction in TAG
groups containing short- and medium-chain fatty acids and a concomitant increase
in those containing long-chain fatty acids. The abundance of five polar lipid
classes including phosphatidylethanolamine, phosphatidylserine,
phosphatidylcholine, lysophosphatidylcholine and glucosylceramide, was found to
be significantly reduced during heat stress. Lysophosphatidylcholine, showing the
greatest reduction in concentration, also displayed a differential response
between heat tolerant and heat susceptible cows during heat stress. This
phospholipid could be used as a heat stress biomarker for dairy cattle. Changes
in TAG profile caused by heat stress are expected to modify the physical
properties of milk fat, whereas the reduction of phospholipids may affect the
nutritional value of milk. The results are discussed in relation to animal
metabolism adaptation in the event of acute heat stress.
PMID- 28424508
TI - Temperature warming strengthens the mutualism between ghost ants and invasive
mealybugs.
AB - Although the exogenous forces that directly affect the mutualisms between ants
and honeydew-producing hemipterans have been well documented, few studies have
been focused on the impacts of environmental warming on ant-hemipteran
interactions. Here, we investigated how temperature warming affects the mutualism
between ghost ant Tapinoma melanocephalum and invasive mealybug Phenacoccus
solenopsis by experimental manipulation of temperature. We found that higher
temperatures have significant direct effects on the growth rate of mealybug
colony, and the positive effect of ant tending on mealybug colony growth is
temperature-dependent. Honeydew excretion by mealybugs was affected by ant
tending and temperature warming, and was significantly increased under higher
temperature. The effect of ant tending on percentage parasitism was also
influenced by temperature warming. Ant performance including tending level,
aggression, activity, and honeydew consumption was enhanced by temperature
warming, which may provide superior protection to the mealybugs. Our results show
that ghost ant-mealybug mutualism is strengthened in a warmer environment. These
findings may facilitate the prediction of how each partner in the ant-hemipteran
enemy interactions responds to increasing temperature.
PMID- 28424509
TI - Evolution of crystal structures in GeTe during phase transition.
AB - We investigated changes in the crystal structure of GeTe during its phase
transition. Using density functional theory (DFT) calculations, four possible
crystal structures were identified: R3m, P1, Cm, and Fm3m. Among these, P1 and Cm
were examined here for the first time. By calculating the internal energy of the
crystal volume change, we verified that P1, R3m, and Cm can coexist in
crystalline GeTe. The X-ray diffraction spectra of annealed and laser-irradiated
GeTe films revealed coexisting P1 or R3m and Cm. In addition, we confirmed that
Cm transforms into P1 or R3m after laser irradiation. The presence of these new
structures was revealed in the crystal Raman spectra. Many of the Raman peaks in
the crystalized GeTe could be explained by the coexistence of various structures.
By calculating the band gaps of these structures, we also found that a structural
transformation induces a change in the crystal resistance, owing to differences
in the band gaps of individual structures. The generation of new crystal
structures suggests a facile phase change and instability during the structural
transformation.
PMID- 28424510
TI - The effect of slow-loaded breathing training on the blood pressure response to
handgrip exercise in patients with isolated systolic hypertension.
AB - Isolated systolic hypertension (ISH) is the most common form of hypertension in
older people. It is characterized by increased resting systolic blood pressure
(sBP) and increased sBP in response to exercise. It has previously been shown
that slow breathing training reduces resting sBP, and the objective of the
present study was to determine whether it also reduced the blood pressure
response to static handgrip exercise. ISH patients aged between 60 and 74 years
were randomly divided into a control group (10 subjects, 4 of which were male)
that breathed normally and a trained group (10 subjects, 4 of which were male)
that trained daily for 8 weeks by slow breathing against an inspiratory
resistance of 18 cmH2O. Before and immediately after training, subjects underwent
a 2-min handgrip test (30% max) followed by 2 min of post-exercise circulatory
occlusion (PECO) to assess metaboreflex activity. Training reduced sBP by 10.6 mm
Hg (95% confidence interval (CI), -16 to -5 mm Hg, P=0.004), but changes were not
observed in the control group. The peak exercise sBP was reduced by 23 mm Hg (95%
CI, -16 to -31 mm Hg, P<0.001), while the increase in the sBP above resting was
reduced by 12.6 mm Hg (95% CI, -6.9 to -18.2 mm Hg, P=0.002). The sBP during PECO
was reduced by 8.9 mm Hg (95% CI, -4 to -14 mm Hg, P=0.008), which is indicative
of reduced metaboreflex activity; no such change was observed in the control
group. The results demonstrate that conventional treatment of older patients with
ISH may be improved in two ways by slow breathing training: resting sBP may be
reduced by 10 mm Hg, more than can be achieved by conventional pharmacological
therapies, while the response to static exercise may be reduced by approximately
twice this value.
PMID- 28424511
TI - Response of peanut Arachis hypogaea roots to the presence of beneficial and
pathogenic fungi by transcriptome analysis.
AB - Entomopathogenic fungus Metarhizium anisopliae obtain survival benefit meanwhile
promote the nutrient absorption of root as an endophyte. However, little is known
concerning molecular mechanisms in the process. We performed the transcriptome
sequencing of A. hypogaea roots inoculated M. anisopliae and pathogenic Fusarium
axysporum, respectively. There were 81323 unigenes from 132023 transcripts. Total
203 differentially expressed genes (DEGs) respond to the two fungi, including
specific 76 and 34 DEGs distributed respectively in M. anisopliae and F.
axysporum treatment. KEGG pathway enrichment for DEGs showed the two top2 were
signal transductions of plant-pathogen interaction and plant hormone. By qRT-PCR,
the mRNA level of 26 genes involved in plant-fungus interaction confirmed the
reliability of the RNA-Seq data. The expression pattern of the key DEGs on
jasmonic acid (JA) or salicylic acid (SA) signaling pathway presented regulating
consistency with JA or SA concentration detected by HPLC-MS. Those significantly
stronger down-regulated DEGs by M. anisopliae thanby F. axysporum linking to
hypersensitive response and negative regulation of defense, and those specific up
regulated genes in M. anisopliae treatment may predict that the less immunity is
conducive to symbiosis F. axysporum may trigger JA-mediated defense regulated by
ERF branch of JA signaling pathway, whereas M. anisopliae does not.
PMID- 28424512
TI - Human umbilical cord plasma proteins revitalize hippocampal function in aged
mice.
AB - Ageing drives changes in neuronal and cognitive function, the decline of which is
a major feature of many neurological disorders. The hippocampus, a brain region
subserving roles of spatial and episodic memory and learning, is sensitive to the
detrimental effects of ageing at morphological and molecular levels. With
advancing age, synapses in various hippocampal subfields exhibit impaired long
term potentiation, an electrophysiological correlate of learning and memory. At
the molecular level, immediate early genes are among the synaptic plasticity
genes that are both induced by long-term potentiation and downregulated in the
aged brain. In addition to revitalizing other aged tissues, exposure to factors
in young blood counteracts age-related changes in these central nervous system
parameters, although the identities of specific cognition-promoting factors or
whether such activity exists in human plasma remains unknown. We hypothesized
that plasma of an early developmental stage, namely umbilical cord plasma,
provides a reservoir of such plasticity-promoting proteins. Here we show that
human cord plasma treatment revitalizes the hippocampus and improves cognitive
function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood
borne factor enriched in human cord plasma, young mouse plasma, and young mouse
hippocampi, appears in the brain after systemic administration and increases
synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion
experiments in aged mice revealed TIMP2 to be necessary for the cognitive
benefits conferred by cord plasma. We find that systemic pools of TIMP2 are
necessary for spatial memory in young mice, while treatment of brain slices with
TIMP2 antibody prevents long-term potentiation, arguing for previously unknown
roles for TIMP2 in normal hippocampal function. Our findings reveal that human
cord plasma contains plasticity-enhancing proteins of high translational value
for targeting ageing- or disease-associated hippocampal dysfunction.
PMID- 28424513
TI - Super-multiplex vibrational imaging.
AB - The ability to visualize directly a large number of distinct molecular species
inside cells is increasingly essential for understanding complex systems and
processes. Even though existing methods have successfully been used to explore
structure-function relationships in nervous systems, to profile RNA in situ, to
reveal the heterogeneity of tumour microenvironments and to study dynamic
macromolecular assembly, it remains challenging to image many species with high
selectivity and sensitivity under biological conditions. For instance,
fluorescence microscopy faces a 'colour barrier', owing to the intrinsically
broad (about 1,500 inverse centimetres) and featureless nature of fluorescence
spectra that limits the number of resolvable colours to two to five (or seven to
nine if using complicated instrumentation and analysis). Spontaneous Raman
microscopy probes vibrational transitions with much narrower resonances (peak
width of about 10 inverse centimetres) and so does not suffer from this problem,
but weak signals make many bio-imaging applications impossible. Although surface
enhanced Raman scattering offers high sensitivity and multiplicity, it cannot be
readily used to image specific molecular targets quantitatively inside live
cells. Here we use stimulated Raman scattering under electronic pre-resonance
conditions to image target molecules inside living cells with very high
vibrational selectivity and sensitivity (down to 250 nanomolar with a time
constant of 1 millisecond). We create a palette of triple-bond-conjugated near
infrared dyes that each displays a single peak in the cell-silent Raman spectral
window; when combined with available fluorescent probes, this palette provides 24
resolvable colours, with the potential for further expansion. Proof-of-principle
experiments on neuronal co-cultures and brain tissues reveal cell-type-dependent
heterogeneities in DNA and protein metabolism under physiological and
pathological conditions, underscoring the potential of this 24-colour (super
multiplex) optical imaging approach for elucidating intricate interactions in
complex biological systems.
PMID- 28424514
TI - Observed quantization of anyonic heat flow.
AB - The quantum of thermal conductance of ballistic (collisionless) one-dimensional
channels is a unique fundamental constant. Although the quantization of the
electrical conductance of one-dimensional ballistic conductors has long been
experimentally established, demonstrating the quantization of thermal conductance
has been challenging as it necessitated an accurate measurement of very small
temperature increase. It has been accomplished for weakly interacting systems of
phonons, photons and electronic Fermi liquids; however, it should theoretically
also hold in strongly interacting systems, such as those in which the fractional
quantum Hall effect is observed. This effect describes the fractionalization of
electrons into anyons and chargeless quasiparticles, which in some cases can be
Majorana fermions. Because the bulk is incompressible in the fractional quantum
Hall regime, it is not expected to contribute substantially to the thermal
conductance, which is instead determined by chiral, one-dimensional edge modes.
The thermal conductance thus reflects the topological properties of the
fractional quantum Hall electronic system, to which measurements of the
electrical conductance give no access. Here we report measurements of thermal
conductance in particle-like (Laughlin-Jain series) states and the more complex
(and less studied) hole-like states in a high-mobility two-dimensional electron
gas in GaAs-AlGaAs heterostructures. Hole-like states, which have fractional
Landau-level fillings of 1/2 to 1, support downstream charged modes as well as
upstream neutral modes, and are expected to have a thermal conductance that is
determined by the net chirality of all of their downstream and upstream edge
modes. Our results establish the universality of the quantization of thermal
conductance for fractionally charged and neutral modes. Measurements of anyonic
heat flow provide access to information that is not easily accessible from
measurements of conductance.
PMID- 28424515
TI - Structure and allosteric inhibition of excitatory amino acid transporter 1.
AB - Human members of the solute carrier 1 (SLC1) family of transporters take up
excitatory neurotransmitters in the brain and amino acids in peripheral organs.
Dysregulation of the function of SLC1 transporters is associated with
neurodegenerative disorders and cancer. Here we present crystal structures of a
thermostabilized human SLC1 transporter, the excitatory amino acid transporter 1
(EAAT1), with and without allosteric and competitive inhibitors bound. The
structures reveal architectural features of the human transporters, such as intra
and extracellular domains that have potential roles in transport function,
regulation by lipids and post-translational modifications. The coordination of
the allosteric inhibitor in the structures and the change in the transporter
dynamics measured by hydrogen-deuterium exchange mass spectrometry reveal a
mechanism of inhibition, in which the transporter is locked in the outward-facing
states of the transport cycle. Our results provide insights into the molecular
mechanisms underlying the function and pharmacology of human SLC1 transporters.
PMID- 28424517
TI - Molecular genetics: Chaperone protein gets personal.
PMID- 28424516
TI - SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1
integrin.
AB - Cancer cells elude anti-tumour immunity through multiple mechanisms, including
upregulated expression of ligands for inhibitory immune checkpoint receptors.
Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic
blockade of signal regulatory protein (SIRP)-alpha, an inhibitory receptor on
macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour
cell elimination in vitro and in vivo, suggesting that blockade of the SIRPalpha
CD47 checkpoint could be useful in treating human cancer. However, the pro
phagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely
unknown. Here we find that macrophages are much more efficient at phagocytosis of
haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in
response to SIRPalpha-CD47 blockade. Using a mouse lacking the signalling
lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell
specific receptors, we determined that phagocytosis of haematopoietic tumour
cells during SIRPalpha-CD47 blockade was strictly dependent on SLAM family
receptors in vitro and in vivo. In both mouse and human cells, this function
required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319),
expressed on macrophages and tumour cell targets. In contrast to most SLAM
receptor functions, SLAMF7-mediated phagocytosis was independent of signalling
lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it
depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18, 19,
20) and utilize signals involving immunoreceptor tyrosine-based activation
motifs. These findings elucidate the mechanism by which macrophages engulf and
destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor
independent function for a SLAM receptor. Lastly, they suggest that patients with
tumours expressing SLAMF7 are more likely to respond to SIRPalpha-CD47 blockade
therapy.
PMID- 28424518
TI - The genetic basis of parental care evolution in monogamous mice.
AB - Parental care is essential for the survival of mammals, yet the mechanisms
underlying its evolution remain largely unknown. Here we show that two sister
species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and
heritable differences in parental behaviour. Using quantitative genetics, we
identify 12 genomic regions that affect parental care, 8 of which have sex
specific effects, suggesting that parental care can evolve independently in males
and females. Furthermore, some regions affect parental care broadly, whereas
others affect specific behaviours, such as nest building. Of the genes linked to
differences in nest-building behaviour, vasopressin is differentially expressed
in the hypothalamus of the two species, with increased levels associated with
less nest building. Using pharmacology in Peromyscus and chemogenetics in Mus, we
show that vasopressin inhibits nest building but not other parental behaviours.
Together, our results indicate that variation in an ancient neuropeptide
contributes to interspecific differences in parental care.
PMID- 28424519
TI - Mechanism of chromatin remodelling revealed by the Snf2-nucleosome structure.
AB - Chromatin remodellers are helicase-like, ATP-dependent enzymes that alter
chromatin structure and nucleosome positions to allow regulatory proteins access
to DNA. Here we report the cryo-electron microscopy structure of chromatin
remodeller Switch/sucrose non-fermentable (SWI2/SNF2) from Saccharomyces
cerevisiae bound to the nucleosome. The structure shows that the two core domains
of Snf2 are realigned upon nucleosome binding, suggesting activation of the
enzyme. The core domains contact each other through two induced Brace helices,
which are crucial for coupling ATP hydrolysis to chromatin remodelling. Snf2
binds to the phosphate backbones of one DNA gyre of the nucleosome mainly through
its helicase motifs within the major domain cleft, suggesting a conserved
mechanism of substrate engagement across different remodellers. Snf2 contacts the
second DNA gyre via a positively charged surface, providing a mechanism to anchor
the remodeller at a fixed position of the nucleosome. Snf2 locally deforms
nucleosomal DNA at the site of binding, priming the substrate for the remodelling
reaction. Together, these findings provide mechanistic insights into chromatin
remodelling.
PMID- 28424520
TI - Decarboxylative alkenylation.
AB - Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or
reductions, has an essential role in the manipulation of organic matter. Despite
its importance, olefin synthesis still relies largely on chemistry introduced
more than three decades ago, with metathesis being the most recent addition. Here
we describe a simple method of accessing olefins with any substitution pattern or
geometry from one of the most ubiquitous and variegated building blocks of
chemistry: alkyl carboxylic acids. The activating principles used in amide-bond
synthesis can therefore be used, with nickel- or iron-based catalysis, to extract
carbon dioxide from a carboxylic acid and economically replace it with an
organozinc-derived olefin on a molar scale. We prepare more than 60 olefins
across a range of substrate classes, and the ability to simplify retrosynthetic
analysis is exemplified with the preparation of 16 different natural products
across 10 different families.
PMID- 28424522
TI - Animal behaviour: How to build a better dad.
PMID- 28424521
TI - Visualizing multistep elevator-like transitions of a nucleoside transporter.
AB - Membrane transporters move substrates across the membrane by alternating access
of their binding sites between the opposite sides of the membrane. An emerging
model of this process is the elevator mechanism, in which a substrate-binding
transport domain moves a large distance across the membrane. This mechanism has
been characterized by a transition between two states, but the conformational
path that leads to the transition is not yet known, largely because the available
structural information has been limited to the two end states. Here we present
crystal structures of the inward-facing, intermediate, and outward-facing states
of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we
determined the structures of multiple intermediate conformations, in which the
transport domain is captured halfway through its elevator motion. Our structures
present a trajectory of the conformational transition in the elevator model,
revealing multiple intermediate steps and state-dependent conformational changes
within the transport domain that are associated with the elevator-like motion.
PMID- 28424523
TI - Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl.
AB - Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and
cohesin into chromatin loops and topologically associated domains, which have
important roles in gene regulation and recombination. By binding to specific
sequences, CTCF defines contact points for cohesin-mediated long-range
chromosomal cis-interactions. Cohesin is also present at these sites, but has
been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops
until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites,
according to this or other models, is unknown. Here we show that the distribution
of cohesin in the mouse genome depends on transcription, CTCF and the cohesin
release factor Wings apart-like (Wapl). In CTCF-depleted fibroblasts, cohesin
cannot be properly recruited to CTCF sites but instead accumulates at
transcription start sites of active genes, where the cohesin-loading complex is
located. In the absence of both CTCF and Wapl, cohesin accumulates in up to 70
kilobase-long regions at 3'-ends of active genes, in particular if these converge
on each other. Changing gene expression modulates the position of these 'cohesin
islands'. These findings indicate that transcription can relocate mammalian
cohesin over long distances on DNA, as previously reported for yeast cohesin,
that this translocation contributes to positioning cohesin at CTCF sites, and
that active genes can be freed from cohesin either by transcription-mediated
translocation or by Wapl-mediated release.
PMID- 28424524
TI - HqiA, a novel quorum-quenching enzyme which expands the AHL lactonase family.
AB - The screening of a metagenomic library of 250,000 clones generated from a
hypersaline soil (Spain) allowed us to identify a single positive clone which
confers the ability to degrade N-acyl homoserine lactones (AHLs). The sequencing
of the fosmid revealed a 42,318 bp environmental insert characterized by 46 ORFs.
The subcloning of these ORFs demonstrated that a single gene (hqiA) allowed AHL
degradation. Enzymatic analysis using purified HqiA and HPLC/MS revealed that
this protein has lactonase activity on a broad range of AHLs. The introduction of
hqiA in the plant pathogen Pectobacterium carotovorum efficiently interfered with
both the synthesis of AHLs and quorum-sensing regulated functions, such as
swarming motility and the production of maceration enzymes. Bioinformatic
analyses highlighted that HqiA showed no sequence homology with the known
prototypic AHL lactonases or acylases, thus expanding the AHL-degrading enzymes
with a new family related to the cysteine hydrolase (CHase) group. The complete
sequence analysis of the fosmid showed that 31 ORFs out of the 46 identified were
related to Deltaproteobacteria, whilst many intercalated ORFs presented high
homology with other taxa. In this sense, hqiA appeared to be assigned to the
Hyphomonas genus (Alphaproteobacteria), suggesting that horizontal gene transfer
had occurred.
PMID- 28424525
TI - Genome-wide detection of copy number variation in Chinese indigenous sheep using
an ovine high-density 600 K SNP array.
AB - Copy number variants (CNVs) represent a form of genomic structural variation
underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP
600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A
total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were
detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1).
We combined our findings with five existing CNVR reports to generate a composite
genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs.
Subsequently, ten novel CNVRs were randomly chosen for further quantitative real
time PCR (qPCR) confirmation, and eight were successfully validated. Gene
functional enrichment revealed that these CNVRs cluster into Gene Ontology (GO)
categories of homeobox and embryonic skeletal system morphogenesis. One CNVR
overlapping with the homeobox transcription factor DLX3 and previously shown to
be associated with curly hair in sheep was identified as the candidate CNV for
the special curly fleece phenotype in Tan sheep. We constructed a Chinese
indigenous sheep genomic CNV map based on the Illumina Ovine SNP 600 K BeadChip
array, providing an important addition to published sheep CNVs, which will be
helpful for future investigations of the genomic structural variations underlying
traits of interest in sheep.
PMID- 28424526
TI - The impact of host sex on the outcome of co-infection.
AB - Males and females vary in many characteristics that typically underlie how well a
host is able to fight infection, such as body-size, immune capacity, or energy
availability. Although well studied in the context of sexual signalling, there is
now growing recognition that these differences can influence aspects of pathogen
evolution as well. Here we consider how co-infection between multiple pathogen
strains is shaped by male-female differences. In natural populations, infections
by more than one pathogen strain or species are believed to be a widespread
occurrence. Using the water flea, Daphnia magna, we exposed genetically identical
males and females to replicated bacterial co-infections. We found that pathogen
transmission and virulence were much higher in females. However, males did not
simply lower average pathogen fitness, but rather the influence of co-infection
was more varied and less defined than in females. We discuss how pathogens may
have more fitness benefits to gain, and consequently to lose, when infecting one
sex over the other.
PMID- 28424527
TI - Unified Alignment of Protein-Protein Interaction Networks.
AB - Paralleling the increasing availability of protein-protein interaction (PPI)
network data, several network alignment methods have been proposed. Network
alignments have been used to uncover functionally conserved network parts and to
transfer annotations. However, due to the computational intractability of the
network alignment problem, aligners are heuristics providing divergent solutions
and no consensus exists on a gold standard, or which scoring scheme should be
used to evaluate them. We comprehensively evaluate the alignment scoring schemes
and global network aligners on large scale PPI data and observe that three
methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically
and biologically coherent alignments. We study the collective behaviour of
network aligners and observe that PPI networks are almost entirely aligned with a
handful of aligners that we unify into a new tool, Ulign. Ulign enables complete
alignment of two networks, which traditional global and local aligners fail to
do. Also, multiple mappings of Ulign define biologically relevant soft
clusterings of proteins in PPI networks, which may be used for refining the
transfer of annotations across networks. Hence, PPI networks are already well
investigated by current aligners, so to gain additional biological insights, a
paradigm shift is needed. We propose such a shift come from aligning all
available data types collectively rather than any particular data type in
isolation from others.
PMID- 28424528
TI - Elucidation of quantitative structural diversity of remarkable rearrangement
regions, shufflons, in IncI2 plasmids.
AB - A multiple DNA inversion system, the shufflon, exists in incompatibility (Inc) I1
and I2 plasmids. The shufflon generates variants of the PilV protein, a minor
component of the thin pilus. The shufflon is one of the most difficult regions
for de novo genome assembly because of its structural diversity even in an
isolated bacterial clone. We determined complete genome sequences, including
those of IncI2 plasmids carrying mcr-1, of three Escherichia coli strains using
single-molecule, real-time (SMRT) sequencing and Illumina sequencing. The
sequences assembled using only SMRT sequencing contained misassembled regions in
the shufflon. A hybrid analysis using SMRT and Illumina sequencing resolved the
misassembled region and revealed that the three IncI2 plasmids, excluding the
shufflon region, were highly conserved. Moreover, the abundance ratio of whole
shufflon structures could be determined by quantitative structural variation
analysis of the SMRT data, suggesting that a remarkable heterogeneity of whole
shufflon structural variations exists in IncI2 plasmids. These findings indicate
that remarkable rearrangement regions should be validated using both long-read
and short-read sequencing data and that the structural variation of PilV in the
shufflon might be closely related to phenotypic heterogeneity of plasmid-mediated
transconjugation involved in horizontal gene transfer even in bacterial clonal
populations.
PMID- 28424529
TI - Surface-dependent scenarios for dissolution-driven motion of growing droplets.
AB - Nano-droplets on a foreign substrate have received increasing attention because
of their technological possible applications, for instance to catalyse the growth
of nanowires. In some cases the droplets can move as a result of a reaction with
the substrate. In this work we show that the substrate orientation, the surface
morphology and the shape of the pits etched in the substrate by the droplets
affect the droplet motion, so that a single mechanism (droplet-induced substrate
dissolution) may lead to several unexpected droplet dynamics. The experiments are
carried out by low energy electron microscopy on Au-Si and Au-Ge, which are model
systems for studying liquid droplet alloys. Studying in-situ the behaviour of Au
droplets on various Si and Ge surfaces, we describe a subtle interplay between
the substrate orientation, the surface defects, and the droplet motion. Our
observations allow a deep understanding of the interfacial mechanisms at the
origin of the alloy formation and the associated droplet motion. These mechanisms
are based on events of substrate dissolution/recrystallization. The outcomes of
this work highlight the importance of the etching anisotropy on the droplet
substrate behaviours, and are essential in the perspective of positioning liquid
alloy droplets used for instance as nanowire catalysts.
PMID- 28424530
TI - Molecular diagnostic assays based on cpn60 UT sequences reveal the geographic
distribution of subgroup 16SrXIII-(A/I)I phytoplasma in Mexico.
AB - Geographically diverse samples from strawberry exhibiting symptoms of Strawberry
Green Petal (SbGP), periwinkle plants with virescence, and blackberry, blueberry,
and raspberry plants displaying yellowing and inedible fruits, were assayed for
the presence of phytoplasma DNA. PCR targeting the 16S rRNA-encoding gene and
chaperonin-60 (cpn60) showed that the plants were infected with phytoplasma
subgroup16SrXIII-(A/I)I (SbGP/MPV). To examine the geographic distribution of
this pathogen in Mexico, we designed an array of cpn60-targeted molecular
diagnostic assays for SbGP/MPV phytoplasma. A fluorescent microsphere
hybridization assay was designed that was capable of detecting SbGP/MPV
phytoplasma in infected plant tissues, successfully differentiating it from other
known phytoplasma cpn60 UT sequences, while identifying a double infection with
SbGP/MPV and aster yellows (16SrI) phytoplasma. Two quantitative assays,
quantitative real-time PCR (qRT-PCR) and droplet digital PCR (ddPCR), gave
similar results in infected samples. Finally, a loop-mediated isothermal
amplification (LAMP) assay provided rapid detection of SbGP/MPV phytoplasma DNA.
Application of these assays revealed that SbGP/MPV phytoplasma is widely
distributed in Central Mexico, with positive samples identified from eleven
localities within three states separated by hundreds of kilometres. These results
also provide tools for determining the presence and geographic distribution of
this pathogen in plant and insect samples in other localities.
PMID- 28424531
TI - Silicon Derived from Glass Bottles as Anode Materials for Lithium Ion Full Cell
Batteries.
AB - Every year many tons of waste glass end up in landfills without proper recycling,
which aggravates the burden of waste disposal in landfill. The conversion from un
recycled glass to favorable materials is of great significance for sustainable
strategies. Recently, silicon has been an exceptional anode material towards
large-scale energy storage applications, due to its extraordinary lithiation
capacity of 3579 mAh g-1 at ambient temperature. Compared with other quartz
sources obtained from pre-leaching processes which apply toxic acids and high
energy-consuming annealing, an interconnected silicon network is directly derived
from glass bottles via magnesiothermic reduction. Carbon-coated glass derived
silicon (gSi@C) electrodes demonstrate excellent electrochemical performance with
a capacity of ~1420 mAh g-1 at C/2 after 400 cycles. Full cells consisting of
gSi@C anodes and LiCoO2 cathodes are assembled and achieve good initial cycling
stability with high energy density.
PMID- 28424533
TI - The Radical Flank Effect and Cross-occupational Collaboration for Technology
Development during a Power Shift.
AB - This 12-month ethnographic study of an early entrant into the U.S. car-sharing
industry demonstrates that when an organization shifts its focus from developing
radical new technology to incrementally improving this technology, the shift may
spark an internal power struggle between the dominant engineering group and a
challenger occupational group such as the marketing group. Analyzing 42 projects
in two time periods that required collaboration between engineering and marketing
during such a shift, we show how cross-occupational collaboration under these
conditions can be facilitated by a radical flank threat, through which the
bargaining power of moderates is strengthened by the presence of a more-radical
group. In the face of a strong threat by radical members of a challenger
occupational group, moderate members of the dominant engineering group may change
their perceptions of their power to resist challengers' demands and begin to
distinguish between the goals of radical versus more-moderate challengers. To
maintain as much power as possible and prevent the more-dramatic change in
engineering occupational goals demanded by radical challengers, moderate
engineers may build a coalition with moderate challengers and collaborate for
incremental technology development.
PMID- 28424532
TI - Stemness and differentiation potential-recovery effects of sinapic acid against
ultraviolet-A-induced damage through the regulation of p38 MAPK and NF-kappaB.
AB - Ultraviolet A (UVA) irradiation exerts negative effects on stemness and
differentiation potential of stem cells. This study aimed to explore the effect
of sinapic acid on UVA-irradiation-induced damages to stemness and
differentiation potential of human-adipose-tissue-derived mesenchymal stem cells
(hAMSCs) and its UVA-antagonist mechanisms. Sinapic acid attenuated UVA-induced
reduction in the proliferative potential and stemness by upregulating OCT4, SOX2,
and NANOG. In addition, sinapic acid significantly recovered UVA-induced
reduction in expression level of hypoxia-inducible factor (HIF)-1alpha. The
antagonist effect of sinapic acid against stemness damage was mediated by
reduceing PGE2 production through inhibition of p38 MAPK and NF-kappaB. Moreover,
sinapic acid attenuated UVA-induced reduction in differentiation potential by
downregulating the expression of macrophage migration inhibitory factor (MIF) and
Kruppel-like factor (KLF) 2 gene while activating AMP-activated protein kinase
(AMPK). UVA-induced inhibition of adipogenic differentiation was mediated by
reducing MIF production through suppression of NF-kappaB. Taken together, these
findings suggest that sinapic acid may ameliorate UVA-irradiation-induced reduced
stemness and differentiation potential of hAMSCs. Therefore, sinapic acid might
have potential as an antagonist agent to attenuate damages caused by UVA.
PMID- 28424534
TI - Corneal flap thickness with the Moria M2 single-use head 90 microkeratome in 72
consecutive LASIK procedures.
AB - PURPOSE: This study aimed to evaluate the accuracy and consistency of corneal
flap thickness in laser-assisted in situ keratomileusis (LASIK) with the Moria M2
single-use head 90 microkeratome. METHODS: The central corneal thickness of 72
(37 right, 35 left) eyes of 37 patients was measured by ultrasonic pachymetry
preoperatively and intraoperatively after flap cut. The Moria M2 single-use head
90 microkeratome was used to create a superior hinged flap in all eyes. The right
eyes were always operated on before the left eyes in each patient, using the same
blade in all bilateral cases. All patients underwent LASIK for myopia and/or
myopic astigmatism using VISX Star S4 platform. RESULTS: The mean preoperative
spherical equivalent refraction was -3.55+/-2.30 D (range: -0.625 to -11.00 D),
preoperative central corneal thickness by ultrasonic pachymetry was 541+/-26.82
um (490-600 um) and steepest K was 44.08+/-1.49 D (40-46.75 D) in all eyes. The
mean flap thickness was 136.97+/-20.07 um (106-192 um), 131.2+/-19.5 um (91-192
um), and 134.16+/-19.85 um (91-192 um) in the right, left, and both eyes,
respectively. A positive significant relationship was found between flap
thickness and preoperative ultrasonic pachymetry thickness. No significant
relationship was found between flap thickness and the age, preoperative spherical
equivalent, and preoperative steepest K. The difference between the first and
second eyes was not significant. There were no major intraoperative and
postoperative complications in all eyes. CONCLUSION: The Moria M2 single-use head
90 microkeratome cut relatively thicker flaps than were intended. The flap
thickness range was quite wide. This was a disadvantage for the accuracy and
consistency of corneal flap thickness.
PMID- 28424535
TI - Human papillomavirus (HPV): systemic treatment with Gene-Eden-VIR/Novirin safely
and effectively clears virus.
AB - PURPOSE: This paper reports the results of a clinical study that tested the
effect of systemic treatment with the botanical product Gene-Eden-VIR/Novirin on
the clearance rate (also called time to clearance) of the human papillomavirus
(HPV). The study compared the clearance rate in treated and untreated individuals
suffering from a symptomatic HPV infection. The data on the untreated individuals
were obtained by reverse engineering of the Kaplan-Meier figures in five
published papers. MATERIALS AND METHODS: The study included 59 treated
participants. All participants were suffering from a symptomatic HPV infection
prior to the commencement of treatment. The treatment was one to four capsules of
Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-12 months. The
study included five groups of external controls with diverse characteristics.
RESULTS: The mean time to clearance in Gene-Eden-VIR/Novirin-treated individuals
was 5.1 months or 151.5 days (95% CI: 4.2-5.9 months or 95% CI: 125.7-177.3 days,
respectively). The median time to clearance was 3.5 months. The mean time to
clearance in the five untreated groups ranged from 6.9 to 20.0 months (P<0.0001
for the difference between treatment group and each untreated group). Also, 100%
of the participants in the treatment group were HPV free at the end of 12 months
vs 53%, 52%, 65%, 20%, and 77% in the untreated control groups. The treated
participants reported no adverse experiences. CONCLUSION: This clinical study has
two major contributions. First, it showed that systemic treatment with the
natural Gene-Eden-VIR/Novirin decreased the time to HPV clearance, increased the
percentage of HPV-free individuals, and caused no adverse experiences in
individuals suffering from a symptomatic HPV infection. Since there are no other
systemic treatments for symptomatic HPV infections, this study presents highly
valuable information on the clinical effects of the first treatment in this
category. Second, the study presents a new method for conducting clinical studies
that addresses one of the major deficiencies associated with the practice of the
randomized controlled trial method.
PMID- 28424536
TI - Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of
cavitary pulmonary tuberculosis: preparation and in vitro characterization.
AB - In this study, we aimed to design controlled-release microspheres for the
treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor
drug delivery and short duration maintained at effective drug concentration
during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid
loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in
water emulsion solvent evaporation method and assessed their in vitro release as
well as the bronchial mucosal retention characteristics. The microspheres are
spherical in shape with a circular concave on the surface. The particle size of
RLPMs was 27.38+/-1.28 MUm. The drug loading of rifapentine and linezolid was
18.51+/-0.26 and 8.42%+/-0.24%, respectively, while the encapsulation
efficiencies were 55.53+/-0.78 and 16.87%+/-0.47%, respectively (n=3). During the
burst release phase of the in vitro release test, 21.37%+/-0.68% rifapentine was
released in 3 days and 43.56%+/-2.54% linezolid was released in 1 day. Then, both
the drugs entered the sustained release phase. Finally, the cumulative percentage
release of rifapentine and linezolid in 14 days was 27.61+/-1.52 and 51.01%+/
3.31%, respectively (n=3). Bronchoscopic observation revealed that the controlled
release microspheres could slowly release the drugs and retain them on the
surface of bronchial mucosa of canines for 20 days. These results indicated that
the fabricated microspheres exhibited a significant sustained release effect and
could effectively retain the drugs on the surface of bronchial mucosa. Therefore,
this study provides a theoretical and practical foundation for the development of
fabricated microspheres loaded with multiple anti-TB drugs in the bronchoscopic
interventional therapy of cavity pulmonary TB.
PMID- 28424537
TI - Awake craniotomy anesthetic management using dexmedetomidine, propofol, and
remifentanil.
AB - INTRODUCTION: Awake craniotomy allows continuous monitoring of patients'
neurological functions during open surgery. Anesthesiologists have to sedate
patients in a way so that they are compliant throughout the whole surgical
procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently,
the use of alpha2-receptor agonist dexmedetomidine as the primary hypnotic
sedative medication is increasing. METHODS: Nine patients undergoing awake
craniotomy were treated with refined monitored anesthesia care (MAC) protocol
consisting of a combination of local anesthesia without scalp block, low-dose
infusion of dexmedetomidine, propofol, and remifentanil, without the need of
airways management. RESULTS: The anesthetic protocol applied in our study has the
advantage of decreasing the dose of each drug and thus reducing the occurrence of
side effects. All patients had smooth and rapid awakenings. The brain remained
relaxed during the entire procedure. CONCLUSION: In our experience, this protocol
is safe and effective during awake brain surgery. Nevertheless, prospective
randomized trials are necessary to confirm the optimal anesthetic technique to be
used.
PMID- 28424538
TI - Metal complexes in cancer therapy - an update from drug design perspective.
AB - In the past, metal-based compounds were widely used in the treatment of disease
conditions, but the lack of clear distinction between the therapeutic and toxic
doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg
in 1960, a milestone in the history of metal-based compounds used in the
treatment of cancers was witnessed. This forms the foundation for the modern era
of the metal-based anticancer drugs. Platinum drugs, such as cisplatin,
carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the
treatment of cancer, but the delay in the therapeutic accomplishment of other
metal-based compounds hampered the progress of research in this field. Recently,
however, there has been an upsurge of activities relying on the structural
information, aimed at improving and developing other forms of metal-based
compounds and nonclassical platinum complexes whose mechanism of action is
distinct from known drugs such as cisplatin. In line with this, many more metal
based compounds have been synthesized by redesigning the existing chemical
structure through ligand substitution or building the entire new compound with
enhanced safety and cytotoxic profile. However, because of increased emphasis on
the clinical relevance of metal-based complexes, a few of these drugs are
currently on clinical trial and many more are awaiting ethical approval to join
the trial. In this review, we seek to give an overview of previous reviews on the
cytotoxic effect of metal-based complexes while focusing more on newly designed
metal-based complexes and their cytotoxic effect on the cancer cell lines, as
well as on new approach to metal-based drug design and molecular target in cancer
therapy. We are optimistic that the concept of selective targeting remains the
hope of the future in developing therapeutics that would selectively target
cancer cells and leave healthy cells unharmed.
PMID- 28424539
TI - beta3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2
cells, which might further promote cholesterol efflux from macrophage foam cells.
AB - OBJECTIVE: The aim of this study was to explore the effects of beta3-adrenoceptor
(beta3-AR) activation on HepG2 cells and its influence on cholesterol efflux from
macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and
treated with the beta3-AR agonist, BRL37344, and antagonist, SR52390A, and the
expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and beta3-AR in the
supernatants and cells was determined. The expression of peroxisome proliferator
activated receptor (PPAR) gamma and PPARalpha in the HepG2 cells was also
assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed
the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol
content of the foam cells was also measured, and the cholesterol efflux from the
macrophages was examined by determining 3H-labeled cholesterol levels. Expression
of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam
cells was also assessed. RESULTS: beta3-AR activation increased ApoA-I expression
in both the HepG2 cells and the supernatants; PPARgamma expression was
upregulated, but PPARalpha expression was not. Treatment with GW9662 abolished
the increased expression of ApoA-I induced by the beta3-AR agonist. The HepG2
cell supernatants decreased the lipid accumulation and increased the cholesterol
efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1
expression, increased in the macrophage foam cells treated with BRL37344-treated
HepG2 cell supernatants. CONCLUSION: Activation of beta3-AR in HepG2 cells
upregulates ApoA-I expression, which might further promote cholesterol efflux
from macrophage foam cells. PPARgamma might be required for the induction of ApoA
I expression.
PMID- 28424540
TI - MC-PPEA as a new and more potent inhibitor of CLP-induced sepsis and pulmonary
inflammation than FK866.
AB - Our previous study indicated that overexpression of nicotinamide
phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown
of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found
that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which
the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed
a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the
effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced
sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP
induced mortality, serum tumor necrosis factor alpha (TNFalpha) levels, pulmonary
myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1beta
messenger RNA levels. In vitro cell permeability and electric cell-substrate
impedance sensing assays demonstrated that MC4 inhibited TNFalpha- and thrombin
mediated pulmonary endothelial cell permeability better than FK866. MC4 also
exerted more potent effects than FK866, at concentrations as low as 0.3 nM, to
attenuate TNFalpha-mediated intracellular cytokine expression, nicotinamide
adenine dinucleotide (NAD+) and its reduced form NADH levels, and nuclear factor
kappa B p65 phosphorylation and nuclear translocation in A549 cells. Our results
strongly suggest that the newly developed MC4 is a more potent suppressor of CLP
induced pulmonary inflammation and sepsis than FK866, with potential clinical
application as a new treatment agent for sepsis and inflammation.
PMID- 28424541
TI - Physician's recommendation and explanation is important in the initiation and
maintenance of allergen immunotherapy.
AB - BACKGROUND: Allergen immunotherapy (AIT) is currently the only immune-modifying
treatment for allergic disease. The clinical efficacy of AIT for the treatment of
allergic rhinitis and bronchial asthma is well documented. However, many factors
including inconvenience, cost, side effects, and adherence influence the
initiation and persistence of AIT, and patients lack knowledge and have
misconceptions about the treatment. OBJECTIVE: We evaluated the knowledge,
attitude, and satisfaction of patients who received AIT. METHODS: We conducted a
retrospective analysis of medical records of 167 patients who received AIT, and
compared the clinical characteristics between conventional immunotherapy (CIT)
and rush immunotherapy (RIT). Ninety-nine patients completed a questionnaire
survey. RESULTS: Of the total 167 patients, 65.9% (n=110) were treated with CIT
and 34.1% (n=57) with RIT. More than half of the patients (68.7%) initiated AIT
according to their physician's recommendation. Frequent hospital visits were the
main barrier for persistence of AIT. RIT patients were younger and started AIT
earlier than CIT patients. The majority (77%) of patients who received AIT were
satisfied, with no significant difference between CIT and RIT groups. RIT and
fewer allergens used in AIT were related with preference for AIT to
pharmacotherapy. The longer duration of AIT was associated with higher treatment
satisfaction. CONCLUSION: A majority of patients initiated AIT by the physician's
recommendation and were satisfied with treatment regardless of CIT or RIT
schedule. Adequate patient education and a strict patient-physician relationship
in early AIT period could improve the effectiveness and compliance of AIT.
PMID- 28424542
TI - Why do psychiatric patients stop antipsychotic medication? A systematic review of
reasons for nonadherence to medication in patients with serious mental illness.
AB - BACKGROUND: Antipsychotic medication reduces the severity of serious mental
illness (SMI) and improves patient outcomes only when medicines were taken as
prescribed. Nonadherence to the treatment of SMI increases the risk of relapse
and hospitalization and reduces the quality of life. It is necessary to
understand the factors influencing nonadherence to medication in order to
identify appropriate interventions. This systematic review assessed the published
evidence on modifiable reasons for nonadherence to antipsychotic medication in
patients with SMI. METHODS: Articles published between January 1, 2005, and
September 10, 2015, were searched on MEDLINE through PubMed. Abstracts were
independently screened by 2 randomly assigned authors for inclusion, and
disagreement was resolved by another author. Selected full-text articles were
divided among all authors for review. RESULTS: A qualitative analysis of data
from 36 articles identified 11 categories of reasons for nonadherence. Poor
insight was identified as a reason for nonadherence in 55.6% (20/36) of studies,
followed by substance abuse (36.1%, 13/36), a negative attitude toward medication
(30.5%, 11/36), medication side effects (27.8%, 10/36), and cognitive impairments
(13.4%, 7/36). A key reason directly associated with intentional nonadherence was
a negative attitude toward medication, a mediator of effects of insight and
therapeutic alliance. Substance abuse was the only reason consistently associated
with unintentional nonadherence, regardless of type and stage of SMI. DISCUSSION:
Although adherence research is inherently biased because of numerous
methodological limitations and specific reasons under investigation, reasons for
nonadherence consistently identified as significant across studies likely reflect
valid existing associations with important clinical implications. CONCLUSION:
This systematic review suggests that a negative attitude toward medication and
substance abuse are consistent reasons for nonadherence to antipsychotic
medication among people with SMI. Adherence enhancement approaches that
specifically target these reasons may improve adherence in a high-risk group.
However, it is also important to identify drivers of poor adherence specific to
each patient in selecting and implementing intervention strategies.
PMID- 28424543
TI - Patient perceptions of a comprehensive telemedicine intervention to address
persistent poorly controlled diabetes.
AB - OBJECTIVE: We studied a telemedicine intervention for persistent poorly
controlled diabetes mellitus (PPDM) that combined telemonitoring, self-management
support, and medication management. The intervention was designed for practical
delivery using existing Veterans Affairs (VA) telemedicine infrastructure. To
refine the intervention and inform the delivery of the intervention in other
settings, we examined participants' experiences. METHODS: We conducted
semistructured interviews with 18 Veterans who completed the intervention. We
analyzed interview text using directed content analysis and categorized themes by
hemoglobin A1c (HbA1c) improvement (<1% or >=1%). RESULTS: Participants generally
reported greater awareness of their blood glucose levels; however, they described
dissatisfaction with the telemonitoring interface and competing demands during
the intervention. Participants with <1% HbA1c improvement reported that these
challenges interfered with their engagement. Participants with >=1% HbA1c
improvement reported new self-management routines despite challenges. CONCLUSION:
Despite competing demands and frustration with the telemonitoring interface, many
participants demonstrated intervention engagement and substantial improvement in
HbA1c ($1%). Differences in engagement may reflect differing capacity to manage
treatment burden. Because it relies on existing infrastructure, this intervention
is a promising model for addressing PPDM within VA. Future work should focus on
optimizing systems' telemedicine infrastructure; while reliance on existing
infrastructure may facilitate practical delivery, and it may also limit
intervention engagement by excessively contributing to treatment burden.
PMID- 28424544
TI - Association of genetic variations in the mitochondrial DNA control region with
presbycusis.
AB - BACKGROUND: The prominent role of mitochondria in the generation of reactive
oxygen species, cell death, and energy production contributes to the importance
of this organelle in the intracellular mechanism underlying the progression of
the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial
DNA (mtDNA) gene expression and coding region variation have frequently been
reported as being associated with the development of presbycusis. The mtDNA
control region regulates gene expression and replication of the genome of this
organelle. To comprehensively understand of the role of mitochondria in the
progression of presbycusis, we compared variations in the mtDNA control region
between subjects with presbycusis and controls. METHODS: A total of 58
presbycusis patients and 220 control subjects were enrolled in the study after
examination by the otolaryngologist and audiology tests. Variations in the mtDNA
control region were investigated by polymerase chain reaction and Sanger
sequencing. RESULTS: A total of 113 sequence variants were observed in mtDNA, and
variants were detected in 100% of patients, with 84% located in hypervariable
regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and
15,954 A>C, were significantly different between presbycusis and control
subjects. CONCLUSION: The statistically significant difference in the frequencies
of four nucleotide variants in the mtDNA control region of presbycusis patients
and controls is in agreement with previous experimental evidence and supports the
role of mitochondria in the intracellular mechanism underlying presbycusis
development. Moreover, these variants have potential as diagnostic markers for
individuals at a high risk of developing presbycusis. The data also suggest the
possible presence of changes in the mtDNA control region in presbycusis, which
could alter regulatory factor binding sites and influence mtDNA gene expression
and copy number.
PMID- 28424545
TI - Efficacy and safety of alcohol septal ablation in patients over 65 years old with
obstructive hypertrophic cardiomyopathy.
AB - BACKGROUND: The performance of alcohol septal ablation (ASA) in elderly
symptomatic patients with drug-refractory obstructive hypertrophic cardiomyopathy
is still to be confirmed. The objective of this study was to compare the efficacy
and safety of ASA in patients under and over 65 years old. METHODS AND RESULTS:
Fifty-one consecutive patients with obstructive hypertrophic cardio-myopathy who
underwent ASA were retrospectively included and reviewed for in-hospital major
acute cardiac events and follow-up. Twenty-eight patients were over 65 years old.
Left ventricular outflow tract obstruction at rest, use of diuretic and average
dose of diuretic were higher in patients over 65 years old. There was no
difference in hospital stay between patients under and over 65 years old. Among
patients over 65 years old, 2 (7%) died before being discharged. Major acute
cardiac events were more frequent in patients over 65 years old in comparison
with younger patients (43% versus 9%, respectively, P=0.007). The average follow
up duration was 16+/-15 months. There was no difference between patients under
and over 65 years old regarding the efficacy of the procedure with a decrease of
the New York Heart Association class of 1.3+/-0.6 and 1.4+/-0.7 (P=0.510) and the
maximum left ventricular outflow tract gradient of 86+/-57 and 81+/-36 mmHg
(P=0.733), respectively. CONCLUSION: Elderly patients have the same benefits as
younger patients after ASA but have more complications including mortality
events.
PMID- 28424546
TI - Perspectives of older people living in long-term care facilities and of their
family members toward advance care planning discussions: a systematic review and
thematic synthesis.
AB - OBJECTIVE: We aimed to search and synthesize qualitative studies exploring the
perspectives of older people living in long-term care facilities and of their
family members about advance care planning (ACP) discussions. METHODS: The
enhancing transparency in reporting the synthesis of qualitative research
(ENTREQ) framework was used to guide the review and report its results. PubMed,
CINAHL, and PsycINFO were searched for studies published between January 2000 and
November 2015. All included studies were assessed for comprehensiveness of
reporting, and a thematic synthesis of their results was performed. RESULTS: The
nine included studies differed in terms of qualitative method used,
comprehensiveness of reporting, and geographical origin. The thematic synthesis
led to the identification of four main themes: 1) plans already made; 2) end-of
life care and decision-making; 3) opinions and attitudes toward ACP; and 4) how,
when, about what, and with whom to do ACP. CONCLUSION: Despite their willingness
to be involved in a shared decision-making process, older residents and their
families still have little experience with ACP. PRACTICAL IMPLICATIONS: In view
of implementing ACP for elders living in long-term care facilities, it would be
important to rethink ACP and also to incorporate their nonmedical preferences,
according to their own priorities.
PMID- 28424547
TI - Omega-3 fatty acid supplementation can improve both symptoms and signs of dry eye
disease.
PMID- 28424548
TI - Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related
to emphysema associated with chronic obstructive pulmonary disease.
AB - BACKGROUND: Cigarette smoking-induced oxidant-antioxidant imbalance is a factor
that contributes to the pathogenesis of COPD through epithelial cell apoptosis.
Irisin is a skeletal muscle cell-derived myokine associated with physical
activity. Irisin is also known to decrease oxidant-induced apoptosis in patients
with diabetes mellitus. However, the correlation between irisin and emphysema in
COPD and its role in epithelial cell apoptosis remains unknown. SUBJECTS AND
METHODS: Forty patients with COPD were enrolled in this study. Pulmonary function
tests and measurements of the percentage of low-attenuation area on high
resolution computed tomography images were performed, and the results were
evaluated for correlation with serum irisin levels. The effect of irisin on
cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a
transcription factor for antioxidants, was also examined in vitro. RESULTS: Serum
irisin levels were significantly correlated with lung diffusing capacity for
carbon monoxide divided by alveolar volume (r=0.56, P<0.01) and percentage of low
attenuation area (r=-0.79, P<0.01). Moreover, irisin significantly enhanced Nrf2
expression (P<0.05) and reduced cigarette-smoke extract-induced A549 cell
apoptosis (P<0.05). CONCLUSION: Decreased serum irisin levels are related to
emphysema in patients with COPD and involved in epithelial apoptosis, resulting
in emphysema. Irisin could be a novel treatment for emphysema in patients with
COPD.
PMID- 28424549
TI - Seasonal variability in clinical care of COPD outpatients: results from the
Andalusian COPD audit.
AB - OBJECTIVES: Clinical practice in chronic obstructive pulmonary disease (COPD) can
be influenced by weather variability throughout the year. To explore the
hypothesis of seasonal variability in clinical practice, the present study
analyzes the results of the 2013-2014 Andalusian COPD audit with regard to
changes in clinical practice according to the different seasons. METHODS: The
Andalusian COPD audit was a pilot clinical project conducted from October 2013 to
September 2014 in outpatient respiratory clinics of hospitals in Andalusia, Spain
(8 provinces with more than 8 million inhabitants) with retrospective data
gathering. For the present analysis, astronomical seasons in the Northern
Hemisphere were used as reference. Bivariate associations between the different
COPD guidelines and the clinical practice changes over the seasons were explored
by using binomial multivariate logistic regression analysis with age, sex,
Charlson comorbidity index, type of hospital, and COPD severity by forced
expiratory volume in 1 second as covariates, and were expressed as odds ratio
(OR) with 95% confidence intervals (CIs). RESULTS: The Andalusian COPD audit
included 621 clinical records from 9 hospitals. After adjusting for covariates,
only inhaler device satisfaction evaluation was found to significantly differ
according to the seasons with an increase in winter (OR, 3.460; 95% CI, 1.469
8.151), spring (OR, 4.215; 95% CI, 1.814-9.793), and summer (OR, 3.371; 95% CI,
1.391-8.169) compared to that in autumn. The rest of the observed differences
were not significant after adjusting for covariates. However, compliance with
evaluating inhaler satisfaction was low. CONCLUSION: The various aspects of
clinical practice for COPD care were found to be quite homogeneous throughout the
year for the variables evaluated. Inhaler satisfaction evaluation, however,
presented some significant variation during the year. Inhaler device satisfaction
should be evaluated during all clinical visits throughout the year for improved
COPD management.
PMID- 28424551
TI - Interprofessional education for internationally educated health professionals: an
environmental scan.
AB - OBJECTIVE: The objective of this environmental scan was to identify Western
Canadian interprofessional education (IPE) resources that currently exist for
internationally educated health professionals (IEHPs). METHODOLOGY: A web-based
search was conducted to identify learning resources meeting defined inclusion
criteria with a particular focus on the resources available in the Western
Canadian provinces. Information was extracted using a standardized template, and
we contacted IEHP programs for additional information if necessary. Members of
the research team reviewed preliminary findings, identified missing information
from their respective provinces, and contacted organizations to fill in any gaps.
RESULTS: The scan identified 26 learning resources for IEHPs in Western Canadian
provinces and 15 in other provinces focused on support for IEHPs to meet their
profession-specific licensing requirements and to acquire knowledge and
competencies relevant to working in the Canadian health care system. Most
learning resources, such as those found in bridging programs for IEHPs, included
an orientation to the Canadian health care system, components of cultural
competence, and at least one aspect of interprofessional competence (eg,
communication skills). None of the 41 learning resources provided comprehensive
training for IEHPs to cover the six interprofessional competency domains defined
in the Canadian Interprofessional Health Collaborative (CIHC) National
Interprofessional Competency Framework. CONCLUSION: The IEHPs learning resources
in Western Canada do not cover all of the interprofessional competencies. This
review points to the value of developing a comprehensive IPE curriculum, based on
the six domains identified in the CIHC National Interprofessional Competency
Framework.
PMID- 28424550
TI - Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with
chitosan/alginate by layer by layer technology for antitumor applications.
AB - Natural polyelectrolyte multilayers of chitosan (CHI) and alginate (ALG) were
alternately deposited on doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid)
(PLGA) nanoparticles (NPs) with layer by layer self-assembly to control drug
release for antitumor activity. Numerous factors which influenced the multilayer
growth on nano-colloidal particles were studied: polyelectrolyte concentration,
NaCl concentration and temperature. Then the growth regime of the CHI/ALG
multilayers was elucidated. The coated NPs were characterized by transmission
electron microscopy, atomic force microscopy, X-ray diffraction and a zeta
potential analyzer. In vitro studies demonstrated an undesirable initial burst
release of DOX-loaded PLGA NPs (DOX-PLGA NPs), which was relieved from 55.12% to
5.78% through the use of the layer by layer technique. The release of DOX
increased more than 40% as the pH of media decreased from 7.4 to 5.0. More
importantly, DOX-PLGA (CHI/ALG)3 NPs had superior in vivo tumor inhibition rates
at 83.17% and decreased toxicity, compared with DOX-PLGA NPs and DOX in solution.
Thus, the presently formulated PLGA-polyelectrolyte NPs have strong potential
applications for numerous controlled anticancer drug release applications.
PMID- 28424552
TI - Prognostic value of circulating tumor cells in the peripheral blood of patients
with esophageal squamous cell carcinoma.
AB - OBJECTIVE: Circulating tumor cells (CTCs) of patients with malignant tumors can
be used as a prognostic marker. However, there are few relevant reports to date
on esophageal squamous cell carcinoma (ESCC). Our study assesses the clinical
significance of CTCs in ESCC patients. PATIENTS AND METHODS: CTCs were detected
in 103 peripheral blood (PB) samples from 59 ESCC patients. Correlation between
CTCs and clinical parameters was analyzed using the chi2 test or Fisher's exact
test. Overall survival (OS) and progression-free survival (PFS) were analyzed
using Kaplan-Meier analysis and univariate and multivariate methods. RESULTS: The
CTC detection rate was 79.7% (47/59) at baseline. The frequency of CTC-positive
patients increased as the disease stage advanced (88.0% in stages III-IV, 58.9%
in stages I-II). CTC counts >=0/7.5 mL of PB were correlated with the degree of
tumor differentiation, tumor infiltration, and lymph node and distant metastases.
Overall, the OS and PFS of patients with CTC counts >=3 or >=5/7.5 mL of PB
before surgery were significantly shorter than those of patients with CTC counts
<3 or <5/7.5 mL. Multivariate analysis showed CTC counts >=5/7.5 mL of PB to be a
strong prognostic indicator of OS (hazard ratio [HR] 12.478; 95% confidence
interval [CI], 8.2-34.3; P<0.05) and PFS (HR 6.524; 95% CI, 1.2-34.3; P<0.05) in
ESCC patients. Patients in whom CTCs changed from positive at baseline to a
negative value after surgery had an excellent prognosis. CONCLUSION: CTCs might
serve as a reference indicator for the prognosis and monitoring of disease
progression and treatment effects in ESCC.
PMID- 28424553
TI - The world of targeted therapies in kidney cancers: pitfalls, tips and tricks.
AB - In the past few years, metastatic renal cell carcinoma prognosis was improved by
the development of molecular targeted therapies (TTs). At the metastatic stage,
the tolerance to treatment is a major concern, not only because of the challenge
of the efficacy/toxicity ratio improvement but also because of the importance of
an optimal adherence to oral treatments. The present case series relates the
issues of dealing with uncommon and sometimes never described side effects of
sunitinib and sorafenib. The first case report deals with grade 3 vomiting during
hemodialysis with concurrent administration of sunitinib. The second case is an
iterative gout attack induced by sunitinib. The third case presents a grade 3
scalp dysesthesia with sorafenib. The fourth case includes an astonishing
efficacy of metronomic (ie, low doses during a long period of time) bevacizumab
in monotherapy. Multidisciplinary management and systematic reporting of
unexpected efficacies and toxicities are needed to better understand TTs real
therapeutic index. Although TTs revolutionized metastatic renal cell cancer
prognosis, they also brought about previously unknown side effects.
Identification and management of these off-target effects may be tricky, and
therefore, comedication must be wisely chosen. As the physiopathology of these
side effects is still unclear, multidisciplinary management and systematic
reporting of toxicities are essential.
PMID- 28424554
TI - Arterial stiffness in hematologic malignancies.
AB - Malignant and cardiovascular disorders are the top causes of mortality worldwide.
This article reviews the main literature data and mechanisms linking hematologic
malignancies and arterial stiffness, focusing on recent experimental and clinical
results. Several links were found in hematologic malignancies between complete
blood count and arterial stiffness. Chemotherapy, especially anthracyclines,
cyclophosphamide and tyrosine kinase inhibitors, as well as radiotherapy and
hematopoietic stem cell transplantation are the main known causes of arterial
stiffness increase in hematologic malignancies. The mechanisms of arterial
stiffness elevation in hematologic malignancies include an increased oxidative
stress, impaired vascular wall homeostasis, endothelial dysfunction and apoptosis
of endothelial cells, overexpression of inflammatory cytokines, accelerated
atherosclerosis, increased blood viscosity and unstable platelet aggregates.
Guidelines regarding cardiovascular health screening and cardiovascular risk
scores are necessary for hematologic cancer survivors in order to improve
prognosis and quality of life of the patients.
PMID- 28424555
TI - HMGB1 is negatively correlated with the development of endometrial carcinoma and
prevents cancer cell invasion and metastasis by inhibiting the process of
epithelial-to-mesenchymal transition.
AB - High-mobility group box protein 1 (HMGB1), a nuclear protein that plays a
significant role in DNA architecture and transcription, was correlated with the
progression of some types of cancer. However, the role of HMGB1 in endometrial
cancer cell invasion and metastasis remains unexplored. HMGB1 expression was
initially assessed by immunohistochemistry and reverse transcription-quantitative
polymerase chain reaction (RT-qPCR) in normal endometrial tissue and endometrial
carcinoma tissue. High expressions of HMGB1 protein were detected in normal
endometrial tissues; however, in endometrial cancer tissues, the expressions of
HMGB1 were found to be very weak. Furthermore, HMGB1 expressions were negatively
correlated with advanced stage and lymph node metastasis in endometrial cancer.
Then by RT-qPCR, Western blot and immunocytochemistry, HMGB1 was also detected in
primary cultured endometrial cells and four kinds of endometrial cancer cell
lines (Ishikawa, HEC-1A, HEC-1B and KLE). We found that the expression of HMGB1
was much higher in normal endometrial cells than in endometrial cancer cells, and
reduced expression levels of HMGB1 were observed especially in the highly
metastatic cell lines. Using lentivirus transfection, HMGB1 small hairpin RNA was
constructed, and this infected the lowly invasive endometrial cancer cell lines,
Ishikawa and HEC-1B. HMGB1 knockdown significantly enhanced the proliferation,
invasion and metastasis of endometrial cancer cells and induced the process of
epithelial-to-mesenchymal transition. These results can contribute to the
development of a new potential therapeutic target for endometrial cancer.
PMID- 28424556
TI - Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role
for the androgen receptor pathway?
AB - The epidemic of insulin resistance, obesity, and metabolic syndrome has led to
the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of
liver disease in the US. Patients with NASH are at an increased risk for hepatic
disease-related morbidity and death, and chronic inflammation in NASH patients
can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in
males than in females, and genetic studies have identified androgen and androgen
receptors (ARs) as partially responsible for the gender disparity in the
development of liver disease and HCC. Although many factors are known to play
important roles in the progression of inflammation in NASH patients, the role of
androgen and AR in the progression of NASH to HCC has been understudied. This
review summarizes the evidence for a potential role of androgen and the AR
pathway in the development of NASH-related HCC and in the treatment of HCC. It
has been proposed that AR plays a role in the progression of HCC: inhibitory
roles in early stages of hepatocarcinogenesis and tumor-promoting roles in
advanced stages. AR can be activated by several pathways, even in the absence of
androgen. While AR has been explored as a potential therapeutic target in HCC,
several clinical trials have failed to demonstrate a clinical benefit of
antiandrogen drugs in HCC. This review discusses the potential reason for these
observations and discuss the potential future trials design in this important
setting.
PMID- 28424557
TI - Vedolizumab: toward a personalized therapy paradigm for people with ulcerative
colitis.
AB - Ulcerative colitis (UC) is a chronic relapsing and remitting inflammatory bowel
disease, with a characteristic leukocytic infiltration of the mucosa.
Immunosuppression including anti-TNF-alpha therapy is a mainstay of treatment for
many; however, systemic immunosuppression is not universally effective and is
associated with potential side effects. The gut-tropic integrin alpha4beta7,
which is expressed on leukocytes, mediates migration from the circulation to the
intestinal mucosa. Vedolizumab is a monoclonal antibody which blocks the egress
of leukocytes via alpha4beta7, preventing accumulation in the mucosa, and
attenuating inflammation without systemic immunosuppression. Vedolizumab has been
evaluated in UC in a phase III trial, demonstrating efficacy as both an induction
and a maintenance agent. In this article, we review the clinical trial data and
also explore the growing body of "real-world" effectiveness data, investigating
response and remission rates of vedolizumab in clinical practice. In addition, we
review the increasing volume of data supporting the reassuring safety profile
associated with vedolizumab.
PMID- 28424558
TI - Parents' relationship to pain during children's cancer treatment - a preliminary
validation of the Pain Flexibility Scale for Parents.
AB - OBJECTIVES: Pain is one of the most frequent and burdensome symptoms for children
with cancer. Psychological acceptance has been shown to be beneficial in chronic
pain. Acceptance-based interventions for experimentally induced pain have been
shown to predict increased pain tolerance and decreased pain intensity. An
acceptance-based pilot study for children with cancer experiencing pain has shown
promising results. Further, parental acceptance has been shown to predict
decreased child distress. To date, no instruments measuring acceptance in the
context of acute pain in children are available. The aim of this study was to
develop and evaluate an instrument to measure acceptance in parents of children
experiencing pain during cancer treatment. METHODS: A test version of the Pain
Flexibility Scale for Parents (PFS-P) was sent to parents of all children
undergoing cancer treatment in Sweden at the time of the study. Exploratory
factor analysis (n=243) examined numerous solutions. Internal consistency, test
retest reliability and convergent validity were calculated. RESULTS: A three
factor Promax solution best represented the data. The subscales were pain
resistance, valued action and pain fusion. Internal consistency was good
(alpha=0.81-0.93), and the total scale and the subscales demonstrated temporal
stability (r=0.76-0.87) and good convergent validity (-0.40 to -0.84).
DISCUSSION: The PFS-P measuring acceptance in parents of children experiencing
pain during cancer treatment is now available, enabling evaluation of acceptance
in the context of acute pain in children. The scale shows good psychometric
properties but needs further validation.
PMID- 28424559
TI - Evidence of both systemic inflammation and neuroinflammation in fibromyalgia
patients, as assessed by a multiplex protein panel applied to the cerebrospinal
fluid and to plasma.
AB - In addition to central hyperexcitability and impaired top-down modulation,
chronic inflammation probably plays a role in the pathophysiology of fibromyalgia
(FM). Indeed, on the basis of both animal experiments and human studies involving
the analysis of cytokines and other inflammation-related proteins in different
body fluids, neuroinflammatory mechanisms are considered to be central to the
pathophysiology of many chronic pain conditions. However, concerning FM, previous
human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked
only at a few predetermined cytokine candidates. Instead of analyzing only a few
substances at a time, we used a new multiplex protein panel enabling simultaneous
analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and
plasma inflammatory profiles of 40 FM patients compared with CSF from healthy
controls (n=10) and plasma from blood donor controls (n=46). Using multivariate
data analysis by projection, we found evidence of both neuroinflammation (as
assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two
groups of proteins (one for CSF and one for plasma) highly discriminating between
patients and controls are presented. Notably, we found high levels of CSF
chemokine CX3CL1 (also known as fractalkine). In addition, previous findings
concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first
time that such an extensive inflammatory profile has been described for FM
patients. Hence, FM seems to be characterized by objective biochemical
alterations, and the lingering characterization of its mechanisms as essentially
idiopathic or even psychogenic should be seen as definitively outdated.
PMID- 28424561
TI - Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine
plus atazanavir, with or without ritonavir, for 144 weeks.
AB - PURPOSE: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir
Induction with Epzicom Study (ARIES) were stratified by gender to compare
treatment responses. METHODS: A total of 369 HIV-infected, antiretroviral-naive
subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r)
whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to
maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within
treatment gender-related efficacy and safety differences were analyzed. RESULTS:
Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline
median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198
cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25
females/155 males) and most other demographics were similar between groups; more
females than males were black (65% vs 25%) and fewer females had baseline HIV-1
RNA >=100,000 copies/mL (41% vs 58%). At week 144, no significant differences
between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL
(ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r,
68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response
analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r,
+344 vs +301 cells/mm3); proportion with treatment-related grade 2-4 adverse
events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to
144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid
changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and
proportions completing the study were similar during the extension phase. Primary
withdrawal reasons were loss to follow-up and pregnancy for females and loss to
follow-up and other for males. CONCLUSION: Over 144 weeks, no significant gender
differences were observed in efficacy, safety, or fasting lipid changes with
abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.
PMID- 28424560
TI - An exploratory study of host polymorphisms in genes that clinically characterize
breast cancer tumors and pretreatment cognitive performance in breast cancer
survivors.
AB - PURPOSE: Inspired by the hypothesis that heterogeneity in the biology of breast
cancers at the cellular level may account for cognitive dysfunction symptom
variability in survivors, the current study explored relationships between host
single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate
genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2,
ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4,
RRM2, and SCUBE2), identified from clinically relevant prognostic multigene
expression profiles for breast cancer, and pretreatment cognitive performance.
PATIENTS AND METHODS: The sample (n=220) was comprised of 138 postmenopausal
women newly diagnosed with early stage breast cancer and 82 postmenopausal age-
and education-matched healthy controls without breast cancer. Cognitive
performance was assessed after primary surgery but prior to initiation of
adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of
neuropsychological tests encompassing eight cognitive function composite domains:
attention, concentration, executive function, mental flexibility, psychomotor
speed, verbal memory, visual memory, and visual working memory. In total, 131
SNPs were included in the analysis. Standard and robust multiple linear
regression modeling was used to examine relationships between each domain and the
presence or absence of one or more minor alleles for each SNP. Genetic
risk/protection scores (GRSs) were calculated for each domain to evaluate the
collective effect of possession of multiple risk/protective alleles. RESULTS:
With the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main
effect and/or SNP by future prescribed treatment group interactions were observed
for every gene between at least one domain and one or more SNPs. All GRSs were
found to be significantly (P<0.001) associated with each respective domain score.
CONCLUSION: Associations between host SNPs and computed GRSs and variability in
pretreatment cognitive function performance support the study hypothesis, and
warrant further investigations to identify biomarkers for breast cancer-related
cognitive dysfunction.
PMID- 28424562
TI - Immunological and hematological reference intervals among HIV-seronegative
pregnant women in northwest Ethiopia.
AB - BACKGROUND: Pregnancy is a state characterized by profound physiological
hematological changes. However, hematological reference intervals being used in
clinical practice in Ethiopia are derived from nonlocal general populations,
despite the significant variations reported previously. The aim of this study was
to determine the immunological and hematological reference intervals in healthy
pregnancy among HIV-seronegative pregnant women in northwest Ethiopia. MATERIALS
AND METHODS: A total of 200 healthy, HIV-seronegative pregnant women were
enrolled from February 2015 to June 2015 in a cross-sectional study setting at
Gondar University Hospital. Sociodemographic and obstetric data were collected
using a structured questionnaire. Blood samples collected from each participant
were used to define the immunological and hematological parameters. The mean,
median, and 95% interval values were calculated for the immunological and
hematological parameters. P-value <0.05 was considered statistically significant
for all variables. RESULTS: This study found that there were changes in CD4+ T
cell count, platelet count, and hematocrit (HCT) values as pregnancy advances.
The calculated combined reference intervals for the absolute CD4+ T-cell count
and platelet count were 712.47-760.67 and 221.25-240.14, respectively. A
progressive decline in the platelet count was observed as pregnancy advanced,
with 95% intervals of 224.53-253.21, 209.50-237.38, and 213.70-247.86 in the
first, second, and third trimesters, respectively (P=0.27). There was a
statistically significant increase in mean (+/-standard deviation [SD]) HCT with
gestational age, being 39.18+/-6.70, 41.96+/-3.70, and 40.53+/-3.77 in the first,
second, and third trimesters, respectively (P=0.03). The overall 95% interval for
hemoglobin (HB) concentration was 12.99-13.36 g/dL, HCT 40.19%-41.49%, mean
corpuscular volume (MCV) 93.33-94.63 fL, and mean corpuscular hemoglobin (MCH)
28.88-34.81 pg. Compared with the reference ranges derived from other studies, we
found considerable variations in CD4+T-cell count, HB, HCT, and MCV values.
CONCLUSION: The findings of this study highlight the differences in
immunohematological profile among pregnant women and nonpregnant women from
Ethiopia and other countries, in addition to suggesting the need for such
establishment of local reference values for different populations.
PMID- 28424563
TI - Traumatic reopening of macular hole following successful surgical repair.
AB - A 75-year-old Caucasian female with a full-thickness macular hole underwent a
successful surgical repair. Vision improved from 20/400 to 20/30 after surgery.
Two years later, the patient presented with a decreased vision after a fall onto
her face with a reopened full-thickness macular hole. Vision decreased to 20/400
and then she underwent a second surgery with an internal limiting membrane
peeling, which resulted in a second successful closure of her macular hole.
Vision following the second surgery was 20/100. Reopening of a surgically
repaired macular hole commonly follows cataract surgery, epiretinal membrane
formation, and development of cystoid macular edema. This case demonstrates that
surgically repaired macular holes may reopen after trauma as well.
PMID- 28424564
TI - New developments in the management of narcolepsy.
AB - Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%
0.18% of the US and Western European populations. Genetic predisposition is
suspected because of narcolepsy's strong association with HLA DQB1*06-02, and
genome-wide association studies have identified polymorphisms in T-cell receptor
loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin
producing neurons; an autoimmune etiology possibly triggered by some
environmental agent may precipitate hypocretin neuronal loss. Current treatment
modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and
cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic
hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of gamma
hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help
sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various
antidepressant medications including norepinephrine serotonin reuptake
inhibitors, selective serotonin reuptake inhibitors, and tricyclic
antidepressants are second-line agents for treating cataplexy. In addition to
SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line
agents for EDS are stimulants such as methylphenidate and extended-release
amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin
based treatments, and immunotherapy to prevent hypocretin neuronal death. Non
hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649,
tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP
386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release
formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical
trials are investigating efficacy and safety of SXB, modafinil, and armodafinil
in children. gamma-amino butyric acid (GABA) modulation with GABAA receptor
agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs
investigated include GABAB agonists (baclofen), melanin-concentrating hormone
antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based
therapies include hypocretin peptide replacement administered either through an
intracerebroventricular route or intranasal route. Hypocretin neuronal transplant
and transforming stem cells into hypothalamic neurons are also discussed in this
article. Immunotherapy to prevent hypocretin neuronal death is reviewed.
PMID- 28424565
TI - Invasive Pneumococcal Disease: Still Lots to Learn and a Need for Standardized
Data Collection Instruments.
AB - Background. Large studies of invasive pneumococcal disease (IPD) are frequently
lacking detailed clinical information. Methods. A population-based 15-year study
of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years
formed the study group. Males outnumbered females and Aboriginal and homeless
persons were overrepresented. High rates of smoking, excessive alcohol use, and
illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had
functional limitations prior to admission. Bacteremia, pneumonia, and meningitis
were the most common major manifestations of IPD. Almost half of the patients had
alteration of mental status at the time of admission and 22% required mechanical
ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke
occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had
echocardiograms, 35% had impaired ventricular function. The overall in-hospital
mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In
addition to immunization, preventative measures need to consider the
sociodemographic features more carefully. A standard set of data need to be
collected so that comparisons can be made from study to study. Future
investigations should target cardiac function and pulmonary embolism prevention
in this population.
PMID- 28424566
TI - Influence of organic molecules on the aggregation of TiO2 nanoparticles in acidic
conditions.
AB - Engineered nanoparticles released into the environment may interact with natural
organic matter (NOM). Surface complexation affects the surface potential, which
in turn may lead to aggregation of the particles. Aggregation of synthetic TiO2
(anatase) nanoparticles in aqueous suspension was investigated at pH 2.8 as a
function of time in the presence of various organic molecules and Suwannee River
fulvic acid (SRFA), using dynamic light scattering (DLS) and high-resolution
transmission electron microscopy (TEM). Results showed that the average
hydrodynamic diameter and zeta-potential were dependent on both concentration and
molecular structure of the organic molecule. Results were also compared with
those of quantitative batch adsorption experiments. Further, a time study of the
aggregation of TiO2 nanoparticles in the presence of 2,3-dihydroxybenzoic acid
(2,3-DHBA) and SRFA, respectively, was performed in order to observe changes in
zeta-potential and particle size over a time period of 9 months. In the 2,3-DHBA
TiO2 system, zeta-potentials decreased with time resulting in charge
neutralization and/or inversion depending on ligand concentration. Aggregate
sizes increased initially to the micrometer size range, followed by
disaggregation after several months. No or very little interaction between SRFA
and TiO2 occurred at the lowest concentrations tested. However, at the higher
concentrations of SRFA, there was an increase in both aggregate size and the
amount of SRFA adsorbed to the TiO2 surface. This was in correlation with the
zeta-potential that decreased with increased SRFA concentration, leading to
destabilization of the system. These results stress the importance of performing
studies over both short and long time periods to better understand and predict
the long-term effects of nanoparticles in the environment.
PMID- 28424567
TI - Access Barriers to Services by Immigrant Mothers of Children with Autism in
Canada.
AB - Equal access for autism services remains suboptimal for diverse groups. In
Canada, little is known about the barriers immigrant mothers face accessing
services and support for their children with developmental disabilities. In this
qualitative study, 21 immigrant mothers of children with Autism, from a diverse
ethno cultural background, were interviewed in Toronto, Canada. We apply House's
(1981) four domains of social support to analyze findings. Structural support
challenges, such as delays in diagnosis, fragmented and dispersed services were
common, followed by instrumental challenges due to loss of social ties and
stigma. Lack of expected support from partners, and negative perceptions of
services, were identified as emotional and perceptive challenges. Focused
attention is required to address inequalities within the context of current
access pathways for autism.
PMID- 28424568
TI - Teacher Awareness and Attitudes Regarding Adolescent Risk Behaviours: a Sample of
Finnish Middle and High School Teachers.
AB - Empirical evidence has shown that youth gamble on both regulated and unregulated
games, despite legislative prohibitions. This study assesses middle and high
school teachers' awareness and attitudes regarding adolescent gambling and other
potentially high-risk behaviours in Finland. A convenience sample of teachers (N
= 157) from 13 provinces participated in the survey. The results suggest that
teachers in Finland were more knowledgeable of the age limits of other adolescent
high-risk behaviours than the legal age for gambling. Teachers were somewhat
familiar with the behaviours and consequences associated with adolescent
gambling. All other risk behaviours were perceived as being more important than
gambling. Teachers' awareness about gambling prevention material in Finnish
schools was limited. Results suggest that initiatives are required to enhance
teachers' knowledge of adolescent problem gambling and its harmful short- and
long-term consequences. School policies and guidelines including gambling
behavior should be implemented in middle and high schools globally.
PMID- 28424570
TI - NANOTECHNOLOGY, NANOMEDICINE; ETHICAL ASPECTS.
AB - Nanotechnology is a field that we often hear of its name nowadays. Altough what
we know about it is soo poor, we admire this field of technlogy, moreover some
societies even argues that nanotechnology will cause second endustrial
revolution. In addition, nanotechnology makes our basic scientific knowledge
upside down and is soo powerfull that it is potent in nearly every scientific
field. Thereby, it is imposible to say that nanotechnology; which is soo
effective on human and human life; will not cause social and ethical outcomes. In
general, the definition of nanotechnology is the reconfiguration of nanomaterials
by human; there also are different definitions according to the history of
nanotechnology and different point of views. First of all, in comparison to the
other tehnology fields, what is the cause of excellence of nanotechnology, what
human can do is to foresee the advantages and disadvantages of it, what are the
roles of developed and developping countries for the progression of
nanotechnology, what is the attitude of nanoethics and what is view of global
politics to nanotechological research according to international regulations are
all the focus of interests of this study. Last but not least, our apprehension
capacity of nanotechnology, our style of adoption and evaluation of it and the
way that how we locate nanotechnology in our lifes and ethical values are the
other focus of interests.
PMID- 28424569
TI - Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine)
as a medicinal plant species: a review on the bioactive components,
pharmacological properties, analytical and biotechnological studies.
AB - Schisandra chinensis Turcz. (Baill.) is a plant species whose fruits have been
well known in Far Eastern medicine for a long time. However, schisandra seems to
be a plant still underestimated in contemporary therapy still in the countries of
East Asia. The article presents latest available information on the chemical
composition of this plant species. Special attention is given to dibenzo
cyclooctadiene lignans. In addition, recent studies of the biological activity of
dibenzocyclooctadiene lignans and schisandra fruit extracts are recapitulated.
The paper gives a short resume of their beneficial effects in biological systems
in vitro, in animals, and in humans, thus underlining their medicinal potential.
The cosmetic properties are depicted, too. The analytical methods used for
assaying schisandra lignans in the scientific studies and also in industry are
also presented. Moreover, special attention is given to the information on the
latest biotechnological studies of this plant species. The intention of this
review is to contribute to a better understanding of the huge potential of the
pharmacological relevance of S. chinensis.
PMID- 28424572
TI - Functional Sensitivity of 2D Simultaneous Multi-Slice Echo-Planar Imaging:
Effects of Acceleration on g-factor and Physiological Noise.
AB - Accelerated data acquisition with simultaneous multi-slice (SMS) imaging for
functional MRI studies leads to interacting and opposing effects that influence
the sensitivity to blood oxygen level-dependent (BOLD) signal changes. Image
signal to noise ratio (SNR) is decreased with higher SMS acceleration factors and
shorter repetition times (TR) due to g-factor noise penalties and saturation of
longitudinal magnetization. However, the lower image SNR is counteracted by
greater statistical power from more samples per unit time and a higher temporal
Nyquist frequency that allows for better removal of spurious non-BOLD high
frequency signal content. This study investigated the dependence of the BOLD
sensitivity on these main driving factors and their interaction, and provides a
framework for evaluating optimal acceleration of SMS-EPI sequences. functional
magnetic resonance imaging (fMRI) data from a scenes/objects visualization task
was acquired in 10 healthy volunteers at a standard neuroscience resolution of 3
mm on a 3T MRI scanner. SMS factors 1, 2, 4, and 8 were used, spanning TRs of
2800 ms to 350 ms. Two data processing methods were used to equalize the number
of samples over the SMS factors. BOLD sensitivity was assessed using g-factors
maps, temporal SNR (tSNR), and t-score metrics. tSNR results show a dependence on
SMS factor that is highly non-uniform over the brain, with outcomes driven by g
factor noise amplification and the presence of high frequency noise. The t-score
metrics also show a high degree of spatial dependence: the lower g-factor noise
area of V1 shows significant improvements at higher SMS factors; the moderate
level g-factor noise area of the parahippocampal place area shows only a trend of
improvement; and the high g-factor noise area of the ventral-medial pre-frontal
cortex shows a trend of declining t-scores at higher SMS factors. This spatial
variability suggests that the optimal SMS factor for fMRI studies is region
dependent. For task fMRI studies done with similar parameters as were used here
(3T scanner, 32-channel RF head coil, whole brain coverage at 3 mm isotropic
resolution), we recommend SMS accelerations of 4x (conservative) to 8x
(aggressive) for most studies and a more conservative acceleration of 2x for
studies interested in anterior midline regions.
PMID- 28424573
TI - Global Sensory Qualities and Aesthetic Experience in Music.
AB - A well-known tradition in the study of visual aesthetics holds that the
experience of visual beauty is grounded in global computational or statistical
properties of the stimulus, for example, scale-invariant Fourier spectrum or self
similarity. Some approaches rely on neural mechanisms, such as efficient
computation, processing fluency, or the responsiveness of the cells in the
primary visual cortex. These proposals are united by the fact that the
contributing factors are hypothesized to be global (i.e., they concern the
percept as a whole), formal or non-conceptual (i.e., they concern form instead of
content), computational and/or statistical, and based on relatively low-level
sensory properties. Here we consider that the study of aesthetic responses to
music could benefit from the same approach. Thus, along with local features such
as pitch, tuning, consonance/dissonance, harmony, timbre, or beat, also global
sonic properties could be viewed as contributing toward creating an aesthetic
musical experience. Several such properties are discussed and their neural
implementation is reviewed in the light of recent advances in neuroaesthetics.
PMID- 28424574
TI - Present Molecular Limitations of ON-Bipolar Cell Targeted Gene Therapy.
AB - Recent studies have demonstrated the safety and efficacy of ocular gene therapy
based on adeno-associated viral vectors (AAVs). Accordingly, a surge in promising
new gene therapies is entering clinical trials, including the first optogenetic
therapy for vision restoration. To date, optogenetic therapies for vision
restoration target either the retinal ganglion cells (GCs) or presynaptic ON
bipolar cells (OBCs). Initiating light responses at the level of the OBCs has
significant advantages over optogenetic activation of GCs. For example, important
neural circuitries in the inner retina, which shape the receptive fields of GCs,
remain intact when activating the OBCs. Current drawbacks of AAV-mediated gene
therapies targeting OBCs include (1) a low transduction efficiency, (2) off
target expression in unwanted cell populations, and (3) a poor performance in
human tissue compared to the murine retina. Here, we examined side-by-side the
performance of three state-of-the art AAV capsid variants, AAV7m8, AAVBP2, and
AAV7m8(Y444F) in combination with the 4xGRM6-SV40 promoter construct in the
healthy and degenerated mouse retina and in human post-mortem retinal explants.
We find that (1) the 4xGRM6-SV40 promoter is not OBC specific, (2) that all AAV
variants possess broad cellular transduction patterns, with differences between
the transduction patterns of capsid variants AAVBP2 and AAV7m8 and, most
importantly, (3) that all vectors target OBCs in healthy tissue but not in the
degenerated rd1 mouse model, potentially limiting the possibilities for an OBC
targeted optogenetic therapy for vision restoration in the blind.
PMID- 28424571
TI - Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma.
AB - Axons can be several orders of magnitude longer than neural somas, presenting
logistical difficulties in cargo trafficking and structural maintenance. Keeping
the axon compartment well supplied with energy also presents a considerable
challenge; even seemingly subtle modifications of metabolism can result in
functional deficits and degeneration. Axons require a great deal of energy, up to
70% of all energy used by a neuron, just to maintain the resting membrane
potential. Axonal energy, in the form of ATP, is generated primarily through
oxidative phosphorylation in the mitochondria. In addition, glial cells
contribute metabolic intermediates to axons at moments of high activity or
according to need. Recent evidence suggests energy disruption is an early
contributor to pathology in a wide variety of neurodegenerative disorders
characterized by axonopathy. However, the degree to which the energy disruption
is intrinsic to the axon vs. associated glia is not clear. This paper will review
the role of energy availability and utilization in axon degeneration in glaucoma,
a chronic axonopathy of the retinal projection.
PMID- 28424575
TI - Contribution of Autonomic Reflexes to the Hyperadrenergic State in Heart Failure.
AB - Heart failure (HF) is a complex syndrome representing the clinical endpoint of
many cardiovascular diseases of different etiology. Given its prevalence,
incidence and social impact, a better understanding of HF pathophysiology is
paramount to implement more effective anti-HF therapies. Based on left ventricle
(LV) performance, HF is currently classified as follows: (1) with reduced
ejection fraction (HFrEF); (2) with mid-range EF (HFmrEF); and (3) with preserved
EF (HFpEF). A central tenet of HFrEF pathophysiology is adrenergic hyperactivity,
featuring increased sympathetic nerve discharge and a progressive loss of
rhythmical sympathetic oscillations. The role of reflex mechanisms in sustaining
adrenergic abnormalities during HFrEF is increasingly well appreciated and
delineated. However, the same cannot be said for patients affected by HFpEF or
HFmrEF, whom also present with autonomic dysfunction. Neural mechanisms of
cardiovascular regulation act as "controller units," detecting and adjusting for
changes in arterial blood pressure, blood volume, and arterial concentrations of
oxygen, carbon dioxide and pH, as well as for humoral factors eventually released
after myocardial (or other tissue) ischemia. They do so on a beat-to-beat basis.
The central dynamic integration of all these afferent signals ensures
homeostasis, at rest and during states of physiological or pathophysiological
stress. Thus, the net result of information gathered by each controller unit is
transmitted by the autonomic branch using two different codes: intensity and
rhythm of sympathetic discharges. The main scope of the present article is to (i)
review the key neural mechanisms involved in cardiovascular regulation; (ii)
discuss how their dysfunction accounts for the hyperadrenergic state present in
certain forms of HF; and (iii) summarize how sympathetic efferent traffic reveal
central integration among autonomic mechanisms under physiological and
pathological conditions, with a special emphasis on pathophysiological
characteristics of HF.
PMID- 28424576
TI - Defensive Vocalizations and Motor Asymmetry Triggered by Disinhibition of the
Periaqueductal Gray in Non-human Primates.
AB - Rapid and reflexive responses to threats are present across phylogeny. The neural
circuitry mediating reflexive defense reactions has been well-characterized in a
variety of species, for example, in rodents and cats, the detection of and
species-typical response to threats is mediated by a network of structures
including the midbrain tectum (deep and intermediate layers of the superior
colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as
the amygdala and hypothalamus. However, relatively little is known about the
functional architecture of defense circuitry in primates. We have previously
reported that pharmacological activation of the DLSC evokes locomotor asymmetry,
defense-associated vocalizations, cowering behavior, escape responses, and attack
of inanimate objects (Holmes et al., 2012; DesJardin et al., 2013; Forcelli et
al., 2016). Here, we sought to determine if pharmacological activation of the PAG
would induce a similar profile of responses. We activated the PAG in three awake,
behaving macaques by microinfusion of GABA-A receptor antagonist, bicuculline
methiodide. Activation of PAG evoked defense-associated vocalizations and
postural/locomotor asymmetry, but not motor defense responses (e.g., cowering,
escape behavior). These data suggest a partial dissociation between the role of
the PAG and the DLSC in the defense network of macaques, but a general
conservation of the role of PAG in defense responses across species.
PMID- 28424577
TI - Investigation of Endocytic Pathways for the Internalization of Exosome-Associated
Oligomeric Alpha-Synuclein.
AB - Misfolding and aggregation of alpha-synuclein (alphasyn) resulting in
cytotoxicity is a hallmark of Parkinson's disease (PD) and related
synucleinopathies. The recent body of evidence indicates that alphasyn can be
released from neuronal cells by nonconventional exocytosis involving
extracellular vesicles (EVs) such as exosomes. The transfer of alphasyn between
cells has been proposed to be an important mechanism of disease propagation in
PD. To date, exosome trafficking mechanisms, including release and cell-cell
transmission, have not been fully described. To gain insight into the mechanisms
involved, exosomes were purified from conditioned media of stable cells secreting
alphasyn oligomers. A novel bimolecular protein complementation assay was used to
detect exosomes containing alphasyn oligomers. Recipient cells were treated with
exosomes containing alphasyn oligomers or "free" non-exosome-associated alphasyn
oligomers and internalization was monitored. We demonstrate that cell-derived
exosome-associated alphasyn oligomers can be efficiently internalized by
recipient cells. Interestingly exosome-free alphasyn oligomers isolated from
conditioned medium were not internalized but remained bound to the extracellular
surface. To investigate the endocytic pathway(s) required for the exosome uptake
different pharmacological inhibitors of caveolin-dependent, clathrin-dependent,
and macropinocytosis pathways were utilized. Surprisingly, none of these pathways
appear to play a significant role in the internalization of exosome-associated
alphasyn oligomers. Finally, the role of heparin sulfate proteoglycans (HSPGs) in
exosome-associated alphasyn internalization was investigated using genetic
approach. Despite previous studies showing HSPGs can modulate internalization of
fibrillar alphasyn, genetic manipulations did not attenuate internalization of
exosome-associated alphasyn oligomers in our hands, suggesting that exosome
associated alphasyn is internalized via an alternative endocytic pathway(s) that
has yet to be elucidated.
PMID- 28424578
TI - The CRB1 Complex: Following the Trail of Crumbs to a Feasible Gene Therapy
Strategy.
AB - Once considered science fiction, gene therapy is rapidly becoming scientific
reality, targeting a growing number of the approximately 250 genes linked to
hereditary retinal disorders such as retinitis pigmentosa and Leber's congenital
amaurosis. Powerful new technologies have emerged, leading to the development of
humanized models for testing and screening these therapies, bringing us closer to
the goal of personalized medicine. These tools include the ability to
differentiate human induced pluripotent stem cells (iPSCs) to create a "retina-in
a-dish" model and the self-formed ectodermal autonomous multi-zone, which can
mimic whole eye development. In addition, highly specific gene-editing tools are
now available, including the CRISPR/Cas9 system and the recently developed
homology-independent targeted integration approach, which allows gene editing in
non-dividing cells. Variants in the CRB1 gene have long been associated with
retinopathies, and more recently the CRB2 gene has also been shown to have
possible clinical relevance with respect to retinopathies. In this review, we
discuss the role of the CRB protein complex in patients with retinopathy. In
addition, we discuss new opportunities provided by stem cells and gene-editing
tools, and we provide insight into how the retinal therapeutic pipeline can be
improved. Finally, we discuss the current state of adeno-associated virus
mediated gene therapy and how it can be applied to treat retinopathies associated
with mutations in CRB1.
PMID- 28424580
TI - The Role of MicroRNA in the Modulation of the Melanocortinergic System.
AB - The central control of energy balance involves a highly regulated neuronal
network within the hypothalamus and the dorsal vagal complex. In these
structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and
to increase energy expenditure. In addition, leptin, a peripheral signal that
relays information regarding body fat content, modulates the activity of
melanocortin pathway neurons including POMC-, Agouti-related peptide
(AgRP)/Neuropeptide Y (NPY)-, melanocortin receptors (MC3R and MC4R)-expressing
neurons. MicroRNAs (miRNAs) are short non-coding RNAs of 22-26 nucleotides that
post-transcriptionally interfere with target gene expression by binding to their
mRNAs. Evidence has demonstrated that miRNAs play important roles in the central
regulation of energy balance. In this context, different studies identified
miRNAs including miR-200 family, miR-103, or miR-488 that could target the genes
of melanocortin pathway. More precisely, these different miRNAs can modulate
energy homeostasis by affecting leptin transduction pathway in the POMC, or
AgRP/NPY neurons. This article reviews the role of identified miRNAs in the
modulation of melanocortin pathway in the context of energy homeostasis.
PMID- 28424579
TI - GRP78 at the Centre of the Stage in Cancer and Neuroprotection.
AB - The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a
multifunctional protein with activities far beyond its well-known role in the
unfolded protein response (UPR) which is activated after endoplasmic reticulum
(ER) stress in the cells. Most of these newly discovered activities depend on its
position within the cell. GRP78 is located mainly in the ER, but it has also been
observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane,
and secreted, although it is dedicated mostly to engage endogenous cytoprotective
processes. Hence, GRP78 may control either UPR and macroautophagy or may
activated phosphatidylinositol 3-kinase (PI3K)/AKT pro-survival pathways. GRP78
influences how tumor cells survive, proliferate, and develop chemoresistance. In
neurodegeneration, endogenous mechanisms of neuroprotection are frequently
insufficient or dysregulated. Lessons from tumor biology may give us clues about
how boosting endogenous neuroprotective mechanisms in age-related
neurodegeneration. Herein, the functions of GRP78 are revealed at the center of
the stage of apparently opposite sites of the same coin regarding cytoprotection:
neurodegeneration and cancer. The goal is to give a comprehensive and critical
review that may serve to guide future experiments to identify interventions that
will enhance neuroprotection.
PMID- 28424582
TI - Hypothalamic Neurogenesis as an Adaptive Metabolic Mechanism.
AB - In the adult brain, well-characterized neurogenic niches are located in the
subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone
(SGZ) of the hippocampus. In both regions, neural precursor cells (NPCs) share
markers of embryonic radial glia and astroglial cells, and in vitro clonal
expansion of these cells leads to neurosphere formation. It has also been more
recently demonstrated that neurogenesis occurs in the adult hypothalamus, a brain
structure that integrates peripheral signals to control energy balance and
dietary intake. The NPCs of this region, termed tanycytes, are ependymal-glial
cells, which comprise the walls of the infundibular recess of the third ventricle
and contact the median eminence. Thus, tanycytes are in a privileged position to
detect hormonal, nutritional and mitogenic signals. Recent studies reveal that in
response to nutritional signals, tanycytes are capable of differentiating into
orexigenic or anorexigenic neurons, suggesting that these cells are crucial for
control of feeding behavior. In this review, we discuss evidence, which suggests
that hypothalamic neurogenesis may act as an additional adaptive mechanism in
order to respond to changes in diet.
PMID- 28424581
TI - Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric
Neuroimaging.
AB - Type 2 diabetes mellitus is associated with accelerated cognitive decline and
various cerebral abnormalities visible on MRI. The exact pathophysiological
mechanisms underlying cognitive decline in diabetes still remain to be
elucidated. In addition to conventional images, MRI offers a versatile set of
novel contrasts, including blood perfusion, neuronal function, white matter
microstructure, and metabolic function. These more-advanced multiparametric MRI
contrasts and the pertaining parameters are able to reveal abnormalities in type
2 diabetes, which may be related to cognitive decline. To further elucidate the
nature of the link between diabetes, cognitive decline, and brain abnormalities,
and changes over time thereof, biomarkers are needed which can be provided by
advanced MRI techniques. This review summarizes to what extent MRI, especially
advanced multiparametric techniques, can elucidate the underlying neuronal
substrate that reflects the cognitive decline in type 2 diabetes.
PMID- 28424583
TI - A Rodent Model of Dynamic Facial Reanimation Using Functional Electrical
Stimulation.
AB - Facial paralysis can be a devastating condition, causing disfiguring facial
droop, slurred speech, eye dryness, scarring and blindness. This study
investigated the utility of closed-loop functional electric stimulation (FES) for
reanimating paralyzed facial muscles in a quantitative rodent model. The right
buccal and marginal mandibular branches of the rat facial nerve were transected
for selective, unilateral paralysis of whisker muscles. Microwire electrodes were
implanted bilaterally into the facial musculature for FES and electromyographic
(EMG) recording. With the rats awake and head-fixed, whisker trajectories were
tracked bilaterally with optical micrometers. First, the relationship between EMG
and volitional whisker movement was quantified on the intact side of the face.
Second, the effect of FES on whisker trajectories was quantified on the paralyzed
side. Third, closed-loop experiments were performed in which the EMG signal on
the intact side triggered FES on the paralyzed side to restore symmetric
whisking. The results demonstrate a novel in vivo platform for developing control
strategies for neuromuscular facial prostheses.
PMID- 28424584
TI - Hif-1alpha Overexpression Improves Transplanted Bone Mesenchymal Stem Cells
Survival in Rat MCAO Stroke Model.
AB - Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious
obstacle impacting on the outcome of cell therapy for cerebral infarction. This
study was aimed to investigate whether modification of BMSCs with hypoxia
inducible factor 1alpha (Hif-1alpha) could enhance the survival of the implanted
BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1alpha
GFP lentiviral vector or Hif-1alpha siRNA. The modified BMSCs were exposed to
oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were
then assessed. An inhibitor of AMPK (compound C) was used to detect whether AMPK
and mTOR were implicated in the functions of Hif-1alpha on BMSCs survival.
Besides, ultrastructure of BMSCs was observed and the expression of autophagy
markers was measured. The modified BMSCs were transplanted into middle cerebral
artery occlusion (MCAO) model of rats, and the cerebral infarction volume and
neurological function was assessed. The results indicated that Hif-1alpha
overexpression protected OGD induced injury by promoting cellular viability and
inhibiting apoptosis. AMPK was activated while mTOR was inactivated by Hif-1alpha
overexpression, and that might be through which Hif-1alpha functioned BMSCs
survival. Hif-1alpha overexpression promoted autophagy; more important, compound
C abolished the induction of Hif-1alpha on autophagy. Transplantation of the
overexpressed Hif-1alpha of BMSCs into the MCAO rats reduced brain infarct volume
and improved neurobehavioral outcome; besides, it inhibited pro-inflammatory
cytokines generation while promoted neurotrophin secretion. In conclusion, Hif
1alpha might be contributed in the survival of BMSCs by regulating the activation
of AMPK and mTOR, as well as by promoting autophagy.
PMID- 28424585
TI - Efr3a Insufficiency Attenuates the Degeneration of Spiral Ganglion Neurons after
Hair Cell Loss.
AB - Sensorineural hearing loss (SNHL) is caused by an irreversible impairment of
cochlear hair cells and subsequent progressive degeneration of spiral ganglion
neurons (SGNs). Eighty-five requiring 3 (Efr3) is a plasma membrane protein
conserved from yeast to human, and knockout of Efr3a was reported to facilitate
the survival of hippocampal newborn neurons in adult mice. Previously, we found
Efr3a expression in the auditory neural pathway is upregulated soon after the
destruction of hair cells. Here we conducted a time-course analysis of drug
caused damage to hearing ability, hair cells and SGNs in Efr3a knocking down mice
(Efr3a-/+, Efr3a KD) and their wild type littermates. Functional examination
showed that both groups of mice suffered from serious hearing loss with a higher
level of severity in wild type (WT) mice. Morphologic observation following drugs
administration showed that both WT and Efr3a KD mice went through progressive
loss of hair cells and SGNs, in association with degenerative changes in the
perikarya, intracellular organelles, cell body conformation in SGNs, and the
changes of SGNs in WT mice were more severe than in Efr3a KD mice. These
beneficial effects of Efr3a KD could be ascribed to an increase in the expression
of some neurotrophic factors and their receptors in Efr3a KD mice. Our results
indicate that Efr3a insufficiency suppresses drug-caused SNHL neurodegeneration
in association with an increase in the expression of some neurotrophic factors
and their receptors, which may be targeted in the treatment of neurodegeneration.
PMID- 28424587
TI - Interactions of the Mechanosensitive Channels with Extracellular Matrix,
Integrins, and Cytoskeletal Network in Osmosensation.
AB - Life is maintained in a sea water-like internal environment. The homeostasis of
this environment is dependent on osmosensory system translation of hydromineral
information into osmotic regulatory machinery at system, tissue and cell levels.
In the osmosensation, hydromineral information can be converted into cellular
reactions through osmoreceptors, which changes thirst and drinking, secretion of
antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at
systemic level as well as cellular metabolic activity and survival status at
tissue level. The key feature of osmosensation is the activation of
mechanoreceptors or mechanosensors, particularly transient receptor potential
vallinoid (TRPV) and canonical (TRPC) family channels, which increases cytosolic
Ca2+ levels, activates osmosensory cells including VP neurons and triggers a
series of secondary reactions. TRPV channels are sensitive to both hyperosmotic
and hyposmotic stimuli while TRPC channels are more sensitive to hyposmotic
challenge in neurons. The activation of TRP channels relies on changes in cell
volume, membrane stretch and cytoskeletal reorganization as well as hydration
status of extracellular matrix (ECM) and activity of integrins. Different
families of TRP channels could be activated differently in response to
hyperosmotic and hyposmotic stimuli in different spatiotemporal orders, leading
to differential reactions of osmosensory cells. Together, they constitute the
osmosensory machinery. The activation of this osmoreceptor complex is also
associated with the activity of other osmolarity-regulating organelles, such as
water channel protein aquaporins, Na-K-2Cl cotransporters, volume-sensitive anion
channels, sodium pump and purinergic receptors in addition to intercellular
interactions, typically astrocytic neuronal interactions. In this article, we
review our current understandings of the composition of osmoreceptors and the
processes of osmosensation.
PMID- 28424586
TI - APP Protein Family Signaling at the Synapse: Insights from Intracellular APP
Binding Proteins.
AB - Understanding the molecular mechanisms underlying amyloid precursor protein
family (APP/APP-like proteins, APLP) function in the nervous system can be
achieved by studying the APP/APLP interactome. In this review article, we focused
on intracellular APP interacting proteins that bind the YENPTY internalization
motif located in the last 15 amino acids of the C-terminal region. These
proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls,
represent APP cytosolic binding partners exhibiting different neuronal functions.
A comparison of FE65 and APP family member mutant mice revealed a shared function
for APP/FE65 protein family members in neurogenesis and neuronal positioning.
Accumulating evidence also supports a role for membrane-associated APP/APLP
proteins in synapse formation and function. Therefore, it is tempting to
speculate that APP/APLP C-terminal interacting proteins transmit APP/APLP
dependent signals at the synapse. Herein, we compare our current knowledge of the
synaptic phenotypes of APP/APLP mutant mice with those of mice lacking different
APP/APLP interaction partners and discuss the possible downstream effects of APP
dependent FE65/FE65L or X11/Mint signaling on synaptic vesicle release, synaptic
morphology and function. Given that the role of X11/Mint proteins at the synapse
is well-established, we propose a model highlighting the role of FE65 protein
family members for transduction of APP/APLP physiological function at the
synapse.
PMID- 28424588
TI - Chaperones as Suppressors of Protein Misfolded Oligomer Toxicity.
AB - Chaperones have long been recognized to play well defined functions such as to:
(i) assist protein folding and promote formation and maintenance of multisubunit
complexes; (ii) mediate protein degradation; (iii) inhibit protein aggregation;
and (iv) promote disassembly of undesired aberrant protein aggregates. In
addition to these well-established functions, it is increasingly clear that
chaperones can also interact with aberrant protein aggregates, such as pre
fibrillar oligomers and fibrils, and inhibit their toxicity commonly associated
with neurodegenerative diseases without promoting their disassembly. In
particular, the evidence collected so far in different labs, exploiting different
experimental approaches and using different chaperones and client aggregated
proteins, indicates the existence of two distinct mechanisms of action mediated
by the chaperones to neutralize the toxicity of aberrant proteins oligomers: (i)
direct binding of the chaperones to the hydrophobic patches exposed on the
oligomer/fibril surface, with resulting shielding or masking of the moieties
responsible for the aberrant interactions with cellular targets; (ii) chaperone
mediated conversion of aberrant protein aggregates into large and more innocuous
species, resulting in a decrease of their surface-to-volume ratio and
diffusibility and in deposits more easily manageable by clearance mechanisms,
such as autophagy. In this review article we will describe the in vitro and in
vivo evidence supporting both mechanisms and how this results in a suppression of
the detrimental effects caused by protein misfolded aggregates.
PMID- 28424589
TI - The Calcium Channel C-Terminal and Synaptic Vesicle Tethering: Analysis by Immuno
Nanogold Localization.
AB - At chemical synapses the incoming action potential triggers the influx of Ca2+
through voltage-sensitive calcium channels (CaVs, typically CaV2.1 and 2.2) and
the ions binds to sensors associated with docked, transmitter filled synaptic
vesicles (SVs), triggering their fusion and discharge. The CaVs and docked SVs
are located within the active zone (AZ) region of the synapse which faces a
corresponding neurotransmitter receptor-rich region on the post-synaptic cell.
Evidence that the fusion of a SV can be gated by Ca2+ influx through a single CaV
suggests that the channel and docked vesicle are linked by one or more molecular
tethers (Stanley, 1993). Short and long fibrous SV-AZ linkers have been
identified in presynaptic terminals by electron microscopy and we recently imaged
these in cytosol-vacated synaptosome 'ghosts.' Using CaV fusion proteins combined
with blocking peptides we previously identified a SV binding site near the tip of
the CaV2.2 C-terminal suggesting that this intracellular channel domain
participates in SV tethering. In this study, we combined the synaptosome ghost
imaging method with immunogold labeling to localize CaV intracellular domains.
L45, raised against the C-terminal tip, tagged tethered SVs often as far as 100
nm from the AZ membrane whereas NmidC2, raised against a C-terminal mid-region
peptide, and C2Nt, raised against a peptide nearer the C-terminal origin,
resulted in gold particles that were proportionally closer to the AZ.
Interestingly, the observation of gold-tagged SVs with NmidC2 suggests a novel SV
binding site in the C-terminal mid region. Our results implicate the CaV C
terminal in SV tethering at the AZ with two possible functions: first, capturing
SVs from the nearby cytoplasm and second, contributing to the localization of the
SV close to the channel to permit single domain gating.
PMID- 28424590
TI - Geometrical Determinants of Neuronal Actin Waves.
AB - Hippocampal neurons produce in their early stages of growth propagative, actin
rich dynamical structures called actin waves. The directional motion of actin
waves from the soma to the tip of neuronal extensions has been associated with
net forward growth, and ultimately with the specification of neurites into axon
and dendrites. Here, geometrical cues are used to control actin wave dynamics by
constraining neurons on adhesive stripes of various widths. A key observable, the
average time between the production of consecutive actin waves, or mean inter
wave interval (IWI), was identified. It scales with the neurite width, and more
precisely with the width of the proximal segment close to the soma. In addition,
the IWI is independent of the total number of neurites. These two results suggest
a mechanistic model of actin wave production, by which the material conveyed by
actin waves is assembled in the soma until it reaches the threshold leading to
the initiation and propagation of a new actin wave. Based on these observations,
we formulate a predictive theoretical description of actin wave-driven neuronal
growth and polarization, which consistently accounts for different sets of
experiments.
PMID- 28424591
TI - Bcl11b-A Critical Neurodevelopmental Transcription Factor-Roles in Health and
Disease.
AB - B cell leukemia 11b (Bcl11b) is a zinc finger protein transcription factor with a
multiplicity of functions. It works as both a genetic suppressor and activator,
acting directly, attaching to promoter regions, as well as indirectly, attaching
to promoter-bound transcription factors. Bcl11b is a fundamental transcription
factor in fetal development, with important roles for the differentiation and
development of various neuronal subtypes in the central nervous system (CNS). It
has been used as a specific marker of layer V subcerebral projection neurons as
well as striatal interneurons. Bcl11b also has critical developmental functions
in the immune, integumentary and cardiac systems, to the extent that Bcl11b
knockout mice are incompatible with extra-uterine life. Bcl11b has been
implicated in a number of disease states including Huntington's disease,
Alzheimer's disease, HIV and T-Cell malignancy, amongst others. Bcl11b is a
fascinating protein whose critical roles in the CNS and other parts of the body
are yet to be fully explicated. This review summarizes the current literature on
Bcl11b and its functions in development, health, and disease as well as future
directions for research.
PMID- 28424593
TI - Phospholipase A2 of Peroxiredoxin 6 Plays a Critical Role in Cerebral
Ischemia/Reperfusion Inflammatory Injury.
AB - Microglia-mediated inflammation is an important step in the progression of
cerebral ischemia/reperfusion injury and the associated production of receptors
of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6
(Prdx6) has been demonstrated as the endogenous antioxidant protein for its
peroxidase properties. However, the role of the independent phospholipase A2
(iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we
evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and
inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33)
would have a critical effect on inflammatory brain damage. We conducted oxygen
glucose deprivation (OGD)/recovery (R) in vitro and middle cerebral artery
occlusion (MCAO) in vivo in a microglia/neuron co-culture system and in rats. In
vitro, we found that Prdx6-iPLA2 activity was associated with the secretion of
neurotoxic inflammatory mediators interleukin1beta (IL-1beta), interleukin-17 (IL
17) and interleukin-23 (IL-23) and elevated expression of Toll-like receptor 2/4
(TLR2/4), leading to the formation of nuclear factor-kappa B (NF-kappaB),
inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglial
cells. In vivo, combined treatment with Prdx6-iPLA2 activity inhibitor MJ33
showed a greater diminution in neurologic deficits, cerebral infarction, brain
water content and inflammatory molecules than Prdx6-siRNA treatment alone. Our
findings provide new insight into Prdx6-iPLA2 function in the brain. Inhibition
of Prdx6-iPLA2 activity by gene therapy and/or pharmacology may constitute a
promising new therapeutic approach to the treatment of stroke.
PMID- 28424594
TI - Overexpression of Human SOD1 Leads to Discrete Defects in the Cerebellar
Architecture in the Mouse.
AB - The human superoxide dismutase 1 (SOD1) gene is responsible for neutralizing
supercharged oxygen radicals within the cell. Mutation in SOD1 gene causes
amyotrophic lateral sclerosis (ALS). Recent studies have shown involvement of the
cerebellum in ALS, although the cerebellar contribution in SOD1 transgenic mice
remains unclear. Using immunohistopathology, we investigated the Purkinje cell
phenotype in the vermis of the SOD1 transgenic mice cerebellum. Calbindin 1
(Calb1) and three well-known zone and stripe markers, zebrin II, HSP25, and
PLCbeta4 have been used to explore possible alteration in zone and stripe. Here
we show that Calb1 expression is significantly reduced in a subset of the
Purkinje cells that is almost aligned with the cerebellar zones and stripes
pattern. The Purkinje cells of SOD1 transgenic mice display a pattern of Calb1
down-regulation, which seems to proceed to Purkinje cell degeneration as the mice
age. The onset of Calb1 down-regulation in Purkinje cells begins from the central
zone and continues into the nodular zone, however it has not been observed in the
anterior and posterior zones. In a subgroup of SOD1 transgenic mice in which gait
unsteadiness was apparent, down-regulation of Calb1 is seen in a subset of
PLCbeta4+ Purkinje cells in the anterior zone. These observations suggest that
the Calb1- subset of Purkinje cells in the anterior zone, which receives
somatosensory input, causes unsteady gait. Our data suggest that human SOD1
overexpression leads to Calb1 down-regulation in the zone and strip pattern and
raise the question of whether SOD1 overexpression leads to Purkinje cells
degeneration.
PMID- 28424595
TI - Gray Matter Atrophy Is Primarily Related to Demyelination of Lesions in Multiple
Sclerosis: A Diffusion Tensor Imaging MRI Study.
AB - Objective: Cortical pathology, periventricular demyelination, and lesion
formation in multiple sclerosis (MS) are related (Hypothesis 1). Factors in the
cerebrospinal fluid close to these compartments could possibly drive the parallel
processes. Alternatively, the cortical atrophy could be caused by remote axonal
transection (Hypothesis 2). Since MRI can differentiate between demyelination and
axon loss, we used this imaging modality to investigate the correlation between
the pattern of diffusion parameter changes in the periventricular- and deep white
matter and the gray matter atrophy. Methods: High-resolution T1-weighted, FLAIR,
and diffusion MRI images were acquired in 52 RRMS patients and 50 healthy, age
matched controls. We used EDSS to estimate the clinical disability. We used Tract
Based Spatial Statistics to compare diffusion parameters (fractional anisotropy,
mean, axial, and radial diffusivity) between groups. We evaluated global brain,
white, and gray matter atrophy with SIENAX. Averaged, standard diffusion
parameters were calculated in four compartment: periventricular lesioned and
normal appearing white matter, non-periventricular lesioned and normal appearing
white matter. PLS regression was used to identify which diffusion parameter and
in which compartment best predicts the brain atrophy and clinical disability.
Results: In our diffusion tensor imaging study compared to controls we found
extensive alterations of fractional anisotropy, mean and radial diffusivity and
smaller changes of axial diffusivity (maximal p > 0.0002) in patients that
suggested demyelination in the lesioned and in the normal appearing white matter.
We found significant reduction in total brain, total white, and gray matter
(patients: 718.764 +/- 14.968, 323.237 +/- 7.246, 395.527 +/- 8.050 cm3,
controls: 791.772 +/- 22.692, 355.350 +/- 10.929, 436.422 +/- 12.011 cm3; mean +/
SE), (p < 0.015; p < 0.0001; p < 0.009; respectively) of patients compared to
controls. The PLS analysis revealed a combination of demyelination-like diffusion
parameters (higher mean and radial diffusivity in patients) in the lesions and in
the non-lesioned periventricular white matter, which best predicted the gray
matter atrophy (p < 0.001). Similarly, EDSS was best predicted by the radial
diffusivity of the lesions and the non-lesioned periventricular white matter, but
axial diffusivity of the periventricular lesions also contributed significantly
(p < 0.0001). Interpretation: Our investigation showed that gray matter atrophy
and white matter demyelination are related in MS but white matter axonal loss
does not significantly contribute to the gray matter pathology.
PMID- 28424592
TI - New Implications for the Melanocortin System in Alcohol Drinking Behavior in
Adolescents: The Glial Dysfunction Hypothesis.
AB - Alcohol dependence causes physical, social, and moral harms and currently
represents an important public health concern. According to the World Health
Organization (WHO), alcoholism is the third leading cause of death worldwide,
after tobacco consumption and hypertension. Recent epidemiologic studies have
shown a growing trend in alcohol abuse among adolescents, characterized by the
consumption of large doses of alcohol over a short time period. Since brain
development is an ongoing process during adolescence, short- and long-term brain
damage associated with drinking behavior could lead to serious consequences for
health and wellbeing. Accumulating evidence indicates that alcohol impairs the
function of different components of the melanocortin system, a major player
involved in the consolidation of addictive behaviors during adolescence and
adulthood. Here, we hypothesize the possible implications of melanocortins and
glial cells in the onset and progression of alcohol addiction. In particular, we
propose that alcohol-induced decrease in alpha-MSH levels may trigger a cascade
of glial inflammatory pathways that culminate in altered gliotransmission in the
ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate
dopaminergic drive in the NAc, contributing to increase the vulnerability to
alcohol dependence and addiction in the adolescence and adulthood.
PMID- 28424596
TI - Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory
Consolidation in Humans.
AB - So far, studies that investigated interference effects of post-learning processes
on episodic memory consolidation in humans have used tasks involving only complex
and meaningful information. Such tasks require reallocation of general or
encoding-specific resources away from consolidation-relevant activities. The
possibility that interference can be elicited using a task that heavily taxes our
limited brain resources, but has low semantic and hippocampal related long-term
memory processing demands, has never been tested. We address this question by
investigating whether consolidation could persist in parallel with an active,
encoding-irrelevant, minimally semantic task, regardless of its high resource
demands for cognitive processing. We distinguish the impact of such a task on
consolidation based on whether it engages resources that are: (1)
general/executive, or (2) specific/overlapping with the encoding modality. Our
experiments compared subsequent memory performance across two post-encoding
consolidation periods: quiet wakeful rest and a cognitively demanding n-Back
task. Across six different experiments (total N = 176), we carefully manipulated
the design of the n-Back task to target general or specific resources engaged in
the ongoing consolidation process. In contrast to previous studies that employed
interference tasks involving conceptual stimuli and complex processing demands,
we did not find any differences between n-Back and rest conditions on memory
performance at delayed test, using both recall and recognition tests. Our results
indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for
episodic memory consolidation; and (2) post-encoding cognitive engagement does
not interfere with memory consolidation when task-performance has minimal
semantic and hippocampally-based episodic memory processing demands. We discuss
our findings with reference to resource and reactivation-led interference
theories.
PMID- 28424598
TI - Editorial: Bridging the Theories of Affordances and Limb Apraxia.
PMID- 28424597
TI - Working Memory after Traumatic Brain Injury: The Neural Basis of Improved
Performance with Methylphenidate.
AB - Traumatic brain injury (TBI) often results in cognitive impairments for patients.
The aim of this proof of concept study was to establish the nature of
abnormalities, in terms of activity and connectivity, in the working memory
network of TBI patients and how these relate to compromised behavioral outcomes.
Further, this study examined the neural correlates of working memory improvement
following the administration of methylphenidate. We report behavioral, functional
and structural MRI data from a group of 15 Healthy Controls (HC) and a group of
15 TBI patients, acquired during the execution of the N-back task. The patients
were studied on two occasions after the administration of either placebo or 30 mg
of methylphenidate. Between group tests revealed a significant difference in
performance when HCs were compared to TBI patients on placebo [F(1, 28) = 4.426,
p < 0.05, eta p2 = 0.136]. This difference disappeared when the patients took
methylphenidate [F(1, 28) = 3.665, p = 0.66]. Patients in the middle range of
baseline performance demonstrated the most benefit from methylphenidate. Changes
in the TBI patient activation levels in the Left Cerebellum significantly and
positively correlated with changes in performance (r = 0.509, df = 13, p = 0.05).
Whole-brain connectivity analysis using the Left Cerebellum as a seed revealed
widespread negative interactions between the Left Cerebellum and parietal and
frontal cortices as well as subcortical areas. Neither the TBI group on
methylphenidate nor the HC group demonstrated any significant negative
interactions. Our findings indicate that (a) TBI significantly reduces the levels
of activation and connectivity strength between key areas of the working memory
network and (b) Methylphenidate improves the cognitive outcomes on a working
memory task. Therefore, we conclude that methylphenidate may render the working
memory network in a TBI group more consistent with that of an intact working
memory network.
PMID- 28424599
TI - Electrophysiological Sequelae of Hemispherotomy in Ipsilateral Human Cortex.
AB - Objectives: Hemispheric disconnection has been used as a treatment of medically
refractory epilepsy and evolved from anatomic hemispherectomy to functional
hemispherectomies to hemispherotomies. The hemispherotomy procedure involves
disconnection of an entire hemisphere with limited tissue resection and is
reserved for medically-refractory epilepsy due to diffuse hemispheric disease.
Although it is thought to be effective by preventing seizures from spreading to
the contralateral hemisphere, the electrophysiological effects of a
hemispherotomy on the ipsilateral hemisphere remain poorly defined. The objective
of this study was to evaluate the effects of hemispherotomy on the
electrophysiologic dynamics in peri-stroke and dysplastic cortex. Methods:
Intraoperative electrocorticography (ECoG) was recorded from ipsilateral cortex
in 5 human subjects with refractory epilepsy before and after hemispherotomy.
Power spectral density, mutual information, and phase-amplitude coupling were
measured from the ECoG signals. Results: Epilepsy was a result of remote
perinatal stroke in three of the subjects. In two of the subjects, seizures were
a consequence of dysplastic tissue: one with hemimegalencephaly and the second
with Rasmussen's encephalitis. Hemispherotomy reduced broad-band power spectral
density in peri-stroke cortex. Meanwhile, hemispherotomy increased power in the
low and high frequency bands for dysplastic cortex. Functional connectivity was
increased in lower frequency bands in peri-stroke tissue but not affected in
dysplastic tissue after hemispherotomy. Finally, hemispherotomy reduced band
specific phase-amplitude coupling in peristroke cortex but not dysplastic cortex.
Significance: Disconnecting deep subcortical connections to peri-stroke cortex
via a hemispherotomy attenuates power of oscillations and impairs the transfer of
information from large-scale distributed brain networks to the local cortex.
Hence, hemispherotomy reduces heterogeneity between neighboring cortex while
impairing phase-amplitude coupling. In contrast, dysfunctional networks in
dysplastic cortex lack the normal connectivity with distant networks. Therefore
hemispherotomy does not produce the same effects.
PMID- 28424601
TI - Editorial: Trends in Neuroergonomics.
PMID- 28424600
TI - Systems, Subjects, Sessions: To What Extent Do These Factors Influence EEG Data?
AB - Lab-based electroencephalography (EEG) techniques have matured over decades of
research and can produce high-quality scientific data. It is often assumed that
the specific choice of EEG system has limited impact on the data and does not add
variance to the results. However, many low cost and mobile EEG systems are now
available, and there is some doubt as to the how EEG data vary across these newer
systems. We sought to determine how variance across systems compares to variance
across subjects or repeated sessions. We tested four EEG systems: two standard
research-grade systems, one system designed for mobile use with dry electrodes,
and an affordable mobile system with a lower channel count. We recorded four
subjects three times with each of the four EEG systems. This setup allowed us to
assess the influence of all three factors on the variance of data. Subjects
performed a battery of six short standard EEG paradigms based on event-related
potentials (ERPs) and steady-state visually evoked potential (SSVEP). Results
demonstrated that subjects account for 32% of the variance, systems for 9% of the
variance, and repeated sessions for each subject-system combination for 1% of the
variance. In most lab-based EEG research, the number of subjects per study
typically ranges from 10 to 20, and error of uncertainty in estimates of the mean
(like ERP) will improve by the square root of the number of subjects. As a
result, the variance due to EEG system (9%) is of the same order of magnitude as
variance due to subjects (32%/sqrt(16) = 8%) with a pool of 16 subjects. The two
standard research-grade EEG systems had no significantly different means from
each other across all paradigms. However, the two other EEG systems demonstrated
different mean values from one or both of the two standard research-grade EEG
systems in at least half of the paradigms. In addition to providing specific
estimates of the variability across EEG systems, subjects, and repeated sessions,
we also propose a benchmark to evaluate new mobile EEG systems by means of ERP
responses.
PMID- 28424602
TI - Assessing the Driver's Current Level of Working Memory Load with High Density
Functional Near-infrared Spectroscopy: A Realistic Driving Simulator Study.
AB - Cognitive overload or underload results in a decrease in human performance which
may result in fatal incidents while driving. We envision that driver assistive
systems which adapt their functionality to the driver's cognitive state could be
a promising approach to reduce road accidents due to human errors. This research
attempts to predict variations of cognitive working memory load levels in a
natural driving scenario with multiple parallel tasks and to reveal predictive
brain areas. We used a modified version of the n-back task to induce five
different working memory load levels (from 0-back up to 4-back) forcing the
participants to continuously update, memorize, and recall the previous 'n' speed
sequences and adjust their speed accordingly while they drove for approximately
60 min on a highway with concurrent traffic in a virtual reality driving
simulator. We measured brain activation using multichannel whole head, high
density functional near-infrared spectroscopy (fNIRS) and predicted working
memory load level from the fNIRS data by combining multivariate lasso regression
and cross-validation. This allowed us to predict variations in working memory
load in a continuous time-resolved manner with mean Pearson correlations between
induced and predicted working memory load over 15 participants of 0.61 [standard
error (SE) 0.04] and a maximum of 0.8. Restricting the analysis to prefrontal
sensors placed over the forehead reduced the mean correlation to 0.38 (SE 0.04),
indicating additional information gained through whole head coverage. Moreover,
working memory load predictions derived from peripheral heart rate parameters
achieved much lower correlations (mean 0.21, SE 0.1). Importantly, whole head
fNIRS sampling revealed increasing brain activation in bilateral inferior frontal
and bilateral temporo-occipital brain areas with increasing working memory load
levels suggesting that these areas are specifically involved in workload-related
processing.
PMID- 28424603
TI - Commentary: Predictions and the brain: how musical sounds become rewarding.
PMID- 28424604
TI - Mapping Critical Language Sites in Children Performing Verb Generation: Whole
Brain Connectivity and Graph Theoretical Analysis in MEG.
AB - A classic left frontal-temporal brain network is known to support language
processes. However, the level of participation of constituent regions, and the
contribution of extra-canonical areas, is not fully understood; this is
particularly true in children, and in individuals who have experienced early
neurological insult. In the present work, we propose whole-brain connectivity and
graph-theoretical analysis of magnetoencephalography (MEG) source estimates to
provide robust maps of the pediatric expressive language network. We examined
neuromagnetic data from a group of typically-developing young children (n = 15,
ages 4-6 years) and adolescents (n = 14, 16-18 years) completing an auditory verb
generation task in MEG. All source analyses were carried out using a linearly
constrained minimum-variance (LCMV) beamformer. Conventional differential
analyses revealed significant (p < 0.05, corrected) low-beta (13-23 Hz) event
related desynchrony (ERD) focused in the left inferior frontal region (Broca's
area) in both groups, consistent with previous studies. Connectivity analyses
were carried out in broadband (3-30 Hz) on time-course estimates obtained at the
voxel level. Patterns of connectivity were characterized by phase locking value
(PLV), and network hubs identified through eigenvector centrality (EVC). Hub
analysis revealed the importance of left perisylvian sites, i.e., Broca's and
Wernicke's areas, across groups. The hemispheric distribution of frontal and
temporal lobe EVC values was asymmetrical in most subjects; left dominant EVC was
observed in 20% of young children, and 71% of adolescents. Interestingly, the
adolescent group demonstrated increased critical sites in the right cerebellum,
left inferior frontal gyrus (IFG) and left putamen. Here, we show that whole
brain connectivity and network analysis can be used to map critical language
sites in typical development; these methods may be useful for defining the
margins of eloquent tissue in neurosurgical candidates.
PMID- 28424605
TI - White Matter Integrity and Treatment-Based Change in Speech Performance in
Minimally Verbal Children with Autism Spectrum Disorder.
AB - We investigated the relationship between imaging variables for two
language/speech-motor tracts and speech fluency variables in 10 minimally verbal
(MV) children with autism. Specifically, we tested whether measures of white
matter integrity-fractional anisotropy (FA) of the arcuate fasciculus (AF) and
frontal aslant tract (FAT)-were related to change in percent syllable-initial
consonants correct, percent items responded to, and percent syllable insertion
errors (from best baseline to post 25 treatment sessions). Twenty-three MV
children with autism spectrum disorder (ASD) received Auditory-Motor Mapping
Training (AMMT), an intonation-based treatment to improve fluency in spoken
output, and we report on seven who received a matched control treatment. Ten of
the AMMT participants were able to undergo a magnetic resonance imaging study at
baseline; their performance on baseline speech production measures is compared to
that of the other two groups. No baseline differences were found between groups.
A canonical correlation analysis (CCA) relating FA values for left- and right
hemisphere AF and FAT to speech production measures showed that FA of the left AF
and right FAT were the largest contributors to the synthetic independent imaging
related variable. Change in percent syllable-initial consonants correct and
percent syllable-insertion errors were the largest contributors to the synthetic
dependent fluency-related variable. Regression analyses showed that FA values in
left AF significantly predicted change in percent syllable-initial consonants
correct, no FA variables significantly predicted change in percent items
responded to, and FA of right FAT significantly predicted change in percent
syllable-insertion errors. Results are consistent with previously identified
roles for the AF in mediating bidirectional mapping between articulation and
acoustics, and the FAT in its relationship to speech initiation and fluency. They
further suggest a division of labor between the hemispheres, implicating the left
hemisphere in accuracy of speech production and the right hemisphere in fluency
in this population. Changes in response rate are interpreted as stemming from
factors other than the integrity of these two fiber tracts. This study is the
first to document the existence of a subgroup of MV children who experience
increases in syllable- insertion errors as their speech develops in response to
therapy.
PMID- 28424606
TI - Bifurcation Analysis on Phase-Amplitude Cross-Frequency Coupling in Neural
Networks with Dynamic Synapses.
AB - We investigate a discrete-time network model composed of excitatory and
inhibitory neurons and dynamic synapses with the aim at revealing dynamical
properties behind oscillatory phenomena possibly related to brain functions. We
use a stochastic neural network model to derive the corresponding macroscopic
mean field dynamics, and subsequently analyze the dynamical properties of the
network. In addition to slow and fast oscillations arising from excitatory and
inhibitory networks, respectively, we show that the interaction between these two
networks generates phase-amplitude cross-frequency coupling (CFC), in which
multiple different frequency components coexist and the amplitude of the fast
oscillation is modulated by the phase of the slow oscillation. Furthermore, we
clarify the detailed properties of the oscillatory phenomena by applying the
bifurcation analysis to the mean field model, and accordingly show that the
intermittent and the continuous CFCs can be characterized by an aperiodic orbit
on a closed curve and one on a torus, respectively. These two CFC modes switch
depending on the coupling strength from the excitatory to inhibitory networks,
via the saddle-node cycle bifurcation of a one-dimensional torus in map (MT1SNC),
and may be associated with the function of multi-item representation. We believe
that the present model might have potential for studying possible functional
roles of phase-amplitude CFC in the cerebral cortex.
PMID- 28424607
TI - Multivariate Analysis of 18F-DMFP PET Data to Assist the Diagnosis of
Parkinsonism.
AB - An early and differential diagnosis of parkinsonian syndromes still remains a
challenge mainly due to the similarity of their symptoms during the onset of the
disease. Recently, 18F-Desmethoxyfallypride (DMFP) has been suggested to increase
the diagnostic precision as it is an effective radioligand that allows us to
analyze post-synaptic dopamine D2/3 receptors. Nevertheless, the analysis of
these data is still poorly covered and its use limited. In order to address this
challenge, this paper shows a novel model to automatically distinguish idiopathic
parkinsonism from non-idiopathic variants using DMFP data. The proposed method is
based on a multiple kernel support vector machine and uses the linear version of
this classifier to identify some regions of interest: the olfactory bulb,
thalamus, and supplementary motor area. We evaluated the proposed model for both,
the binary separation of idiopathic and non-idiopathic parkinsonism and the
multigroup separation of parkinsonian variants. These systems achieved accuracy
rates higher than 70%, outperforming DaTSCAN neuroimages for this purpose. In
addition, a system that combined DaTSCAN and DMFP data was assessed.
PMID- 28424608
TI - Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and
Iron Metabolism in Parkinson' Disease.
AB - Disrupted iron metabolism has been implicated in the pathogenesis of Parkinson's
disease (PD), a progressive neurodegenerative disorder that severely affects
movement and coordination, yet the molecular mechanisms underlying this
association remain unknown. To this end, we performed a transcriptomic meta
analysis of four blood microarrays in PD. We observed a significant
downregulation of genes related to hemoglobin including, hemoglobin delta (HBD),
alpha hemoglobin stabilizing protein (ASHP), genes implicated in iron metabolism
including, solute carrier family 11 member 2 (SLC11A2), ferrochelatase (FECH),
and erythrocyte-specific genes including erythrocyte membrane protein (EPB42),
and 5'-aminolevulinate synthase 2 (ALAS2). Pathway and network analysis
identified enrichment in processes related to mitochondrial membrane, oxygen
transport, oxygen and heme binding, hemoglobin complex, erythrocyte development,
tetrapyrrole metabolism and the spliceosome. Collectively, we identified a
subnetwork of genes in blood that may provide a molecular explanation for the
disrupted hemoglobin and iron metabolism in the pathogenesis of PD.
PMID- 28424609
TI - A Neurochemical Basis for Phenotypic Differentiation in Alzheimer's Disease?
Turing's Morphogens Revisited.
PMID- 28424610
TI - Characterizing Brain Iron Deposition in Patients with Subcortical Vascular Mild
Cognitive Impairment Using Quantitative Susceptibility Mapping: A Potential
Biomarker.
AB - The presence and pattern of iron accumulation in subcortical vascular mild
cognitive impairment (svMCI) and their effects on cognition have rarely been
investigated. We aimed to examine brain iron deposition in svMCI subjects using
quantitative susceptibility mapping (QSM). Moreover, we aimed to investigate the
correlation between brain iron deposition and the severity of cognitive
impairment as indicated by z-scores. We recruited 20 subcortical ischemic
vascular disease (SIVD) patients who fulfilled the criteria for svMCI. The
control group comprised 19 SIVD patients without cognitive impairment. The SIVD
and control groups were matched based on age, gender, and years of education.
Both groups underwent QSM using a 3.0T MRI system. Susceptibility maps were
reconstructed from in vivo data, which were acquired with a three-dimensional
spoiled gradient recalled sequence. Then, regions of interest were drawn manually
on the map of each subject. The inter-group differences of susceptibility values
were explored in deep gray matter nuclei, including the bilateral pulvinar
nucleus of the thalamus, head of caudate nucleus, globus pallidus, putamen,
hippocampus, substantia nigra, and red nucleus. The correlations between regional
iron deposition and composite z-score, memory z-score, language z-score,
attention-executive z-score and visuospatial z-score were assessed using partial
correlation analysis, with patient age and gender as covariates. Compared with
the control, the svMCI group had elevated susceptibility values within the
bilateral hippocampus and right putamen. Furthermore, the susceptibility value in
the right hippocampus was negatively correlated with memory z-score and
positively correlated with language z-score. The susceptibility value in the
right putamen was negatively correlated with attention-executive z-score in the
svMCI group. However, composite z-score were unrelated to susceptibility values.
Our results suggest that brain iron deposition has clinical relevance as a
biomarker for cognition. In addition, our results highlight the importance of
iron deposition in understanding svMCI-associated cognitive deficits in addition
to conventional MRI markers.
PMID- 28424611
TI - Modafinil-Induced Changes in Functional Connectivity in the Cortex and Cerebellum
of Healthy Elderly Subjects.
AB - In the past few years, cognitive enhancing drugs (CEDs) have gained growing
interest and the focus of investigations aimed at exploring their use to
potentiate the cognitive performances of healthy individuals. Most of this
exploratory CED-related research has been performed on young adults. However,
CEDs may also help to maintain optimal brain functioning or compensate for subtle
and or subclinical deficits associated with brain aging or early-stage dementia.
In this study, we assessed effects on resting state brain activity in a group of
healthy elderly subjects undergoing acute administration of modafinil, a
wakefulness-promoting agent. To that aim, participants (n = 24) were investigated
with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and
after the administration of a single dose (100 mg) of modafinil. Effects were
compared to age and size-matched placebo group. Rs-fMRI effects were assessed,
employing a graph-based approach and Eigenvector Centrality (EC) analysis, by
taking in account topological changes occurring in functional brain networks. The
main finding of the study is that modafinil promotes enhanced centrality, a
measure of the importance of nodes within functional networks, of the bilateral
primary visual (V1) cortex. EC analysis also revealed that modafinil-treated
subjects show increased functional connectivity between the V1 and specific
cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal
sulcus and left middle frontal gyrus) regions. Present findings provide
functional data supporting the hypothesis that modafinil can modulate the cortico
cerebellar connectivity of the aging brain.
PMID- 28424612
TI - An Examination of Brain Abnormalities and Mobility in Individuals with Mild
Cognitive Impairment and Alzheimer's Disease.
AB - Background: Mobility changes are concerning for elderly patients with cognitive
decline. Given frail older individuals' vulnerability to injury, it is critical
to identify contributors to limited mobility. Objective: To examine whether
structural brain abnormalities, including reduced gray matter volume and white
matter hyperintensities, would be associated with limited mobility among
individuals with cognitive impairment, and to determine whether cognitive
impairment would mediate this relationship. Methods: Thirty-four elderly
individuals with mild cognitive impairment (MCI) and Alzheimer's disease
underwent neuropsychological evaluation, mobility assessment, and structural
brain neuroimaging. Linear regression was conducted with predictors including
gray matter volume in six regions of interest (ROI) and white matter
hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower
gray matter volume in caudate nucleus was associated with slower speed on a
functional mobility task. Higher cerebellar volume was also associated with
slower functional mobility. White matter hyperintensity burden was not
significantly associated with mobility. Conclusion: Our findings provide evidence
for associations between subcortical gray matter volume and speed on a functional
mobility task among cognitively impaired individuals.
PMID- 28424613
TI - The Relationship between Cerebral Small Vessel Disease, Hippocampal Volume and
Cognitive Functioning in Patients with COPD: An MRI Study.
AB - The neural correlates of cognitive impairment in chronic obstructive pulmonary
disease (COPD) are not yet understood. Structural brain abnormalities could
possibly be associated with the presence of cognitive impairment through
cigarette smoke, inflammation, vascular disease, or hypoxemia in these patients.
This study aimed to investigate whether macrostructural brain magnetic resonance
imaging (MRI) features of cerebral small vessel disease (SVD) and hippocampal
volume (HCV) are related to cognitive performance in patients with COPD. A
subgroup of cognitively high and low-performing COPD patients of the COgnitive-PD
study, underwent a brain 3T MRI. SVD as a marker of vascular damage was assessed
using qualitative visual rating scales. HCV as a marker of neurodegeneration was
assessed using the learning embedding for atlas propagation (LEAP) method.
Features of SVD and HCV were compared between cognitively high and low-performing
individuals using Mann Whitney U tests and independent samples t-tests,
respectively. No group differences were reported between 25 high-performing (mean
age 60.3 (standard deviation [SD] 9.7) years; 40.0% men; forced expiratory volume
in first second [FEV1] 50.1% predicted) and 30 low-performing patients with COPD
(mean age 60.6 (SD 6.8) years; 53.3% men; FEV1 55.6% predicted) regarding
demographics, clinical characteristics, comorbidities and the presence of the SVD
features and HCV. To conclude, the current study does not provide evidence for a
relationship between cerebral SVD and HCV and cognitive functioning in patients
with COPD. Additional studies will be needed to determine other possible
mechanisms of cognitive impairment in patients with COPD, including
microstructural brain changes and inflammatory-, hormonal-, metabolic- and
(epi)genetic factors.
PMID- 28424614
TI - Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring
of Patients with Late-onset Alzheimer's Disease.
AB - Early neuropathological changes characteristic of late-onset Alzheimer's disease
(LOAD) involve brain stem and limbic structures that regulate neurovegetative
functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging
biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized
that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O
LOAD) would display a series of circadian rhythm abnormalities prior to the onset
of objective cognitive alterations. We tested 31 children of patients with LOAD
(O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease
(control subjects, CS) with basic tests of cognitive function, as well as
actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily
temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in
verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 +/-
0.4 vs. 8.6 +/- 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's
vocabulary 51.4 +/- 1.3 vs. 44.3 +/- 1.5, t = 2.49, df = 49, p < 0.001) compared
to CS, even though all participants had results within the clinically normal
range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 +/- 0.47 h
vs. 3.8 +/- 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O
LOAD was associated with a series of cardiac autonomic sleep-wake variables;
specifically indicators of greater sympathetic activity at night were related to
poorer cognition. The present results suggest sleep pattern deserves further
study as a potential neurobiological signature in LOAD, even in middle-aged, at
risk individuals.
PMID- 28424615
TI - HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by
Regulating Bile Acids Metabolism Homeostasis.
AB - Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical
usage is often limited by the induction of severe gastrointestinal (GI) toxicity,
especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the
treatment of GI ailments, has been proved could significantly ameliorate the
intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced
toxicity and the modulation effects of HQD, a previous untargeted metabolomics
study was performed and the results indicated that HQD may protect the GI tract
by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted
assays are often less sensitive and/or efficient. In order to further confirm our
previous findings, here in this paper, serum and tissues metabolic profiles of 17
BAs were analyzed using liquid chromatography-tandem mass spectrometry based
targeted metabolomics. The results indicated that serum and tissues levels of
most BAs were significantly decreased after CPT-11 administration, except some
hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI
toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that
the BAs pool size remained unchanged, the balance of BAs had shifted leading to
decreased toxicity after HQD treatment. The present study demonstrated for the
first time that the precise interaction between HQD, CPT-11-induced intestinal
toxicity and BAs' homeostasis.
PMID- 28424616
TI - Whole Blood Cytokine Response to Local Traffic-Related Particulate Matter in
Peruvian Children With and Without Asthma.
AB - This study sought to investigate if acute phase immune responses of whole blood
from Peruvian children with controlled and uncontrolled asthma differed from
children without asthma, following exposure to traffic-related particulate matter
(TRPM). TRPM, including particulate matter from diesel combustion, has been shown
to stimulate acute airway inflammation in individuals with and without asthma.
For this study, a whole blood assay (WBA) was used to test peripheral whole blood
samples from 27 children with asthma, and 12 without asthma. Participant blood
samples were stimulated, ex vivo, for 24-h with an aqueous extract of TRPM that
was collected near study area highways in Lima, Peru. All participant blood
samples were tested against the same TRPM extract, in addition to purified
bacterial endotoxin and pyrogen-free water, which served as positive and negative
WBA controls, respectively. The innate and adaptive cytokine responses were
evaluated in cell-free supernatants of the whole blood incubations. Comparatively
similar levels were recorded for nine out of the 10 cytokines measured [e.g., -
Interleukin (IL)-1beta, IL-6, IL-10], regardless of study participant asthma
status. However, IL-8 levels in TRPM-stimulated blood from children with
uncontrolled asthma were diminished, compared to subjects without asthma (633
pg/ml vs. 1,023 pg/ml, respectively; p < 0.01); IL-8 responses for subjects with
controlled asthma were also reduced, but to a lesser degree (799 pg/ml vs. 1,023
pg/ml, respectively; p = 0.10). These relationships were present before, and
after, adjusting for age, sex, obesity/overweight status, C-reactive protein
levels, and residential proximity to the study area's major roadway. For tests
conducted with endotoxin, there were no discernible differences in cytokine
response between groups, for all cytokines measured. The WBA testing conducted
for this study highlighted the capacity of the TRPM extract to potently elicit
the release of IL-8 from the human whole blood system. Although the small sample
size of the study limits the capacity to draw definitive conclusions, the IL-8
responses suggest that that asthma control may be associated with the regulation
of a key mediator in neutrophil chemotaxis, at a systemic level, following
exposure to PM derived from traffic-related sources.
PMID- 28424617
TI - Targeting Bile Acid Receptors: Discovery of a Potent and Selective Farnesoid X
Receptor Agonist as a New Lead in the Pharmacological Approach to Liver Diseases.
AB - Bile acid (BA) receptors represent well-defined targets for the development of
novel therapeutic approaches to metabolic and inflammatory diseases. In the
present study, we report the generation of novel C-3 modified 6-ethylcholane
derivatives. The pharmacological characterization and molecular docking studies
for the structure-activity rationalization, allowed the identification of 3beta
azido-6alpha-ethyl-7alpha-hydroxy-5beta-cholan-24-oic acid (compound 2), a potent
and selective FXR agonist with a nanomolar potency in transactivation assay and
high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen
assay. In vitro, compound 2 was completely inactive towards common off-targets
such as the nuclear receptors PPARalpha, PPARgamma, LXRalpha, and LXRbeta and the
membrane G-coupled BA receptor, GPBAR1. This compound when administered in vivo
exerts a robust FXR agonistic activity increasing the liver expression of FXR
target genes including SHP, BSEP, OSTalpha, and FGF21, while represses the
expression of CYP7A1 gene that is negatively regulated by FXR. Collectively these
effects result in a significant reshaping of BA pool in mouse. In summary,
compound 2 represents a promising candidate for drug development in liver and
metabolic disorders.
PMID- 28424618
TI - Pharmacological and Biochemical Characterization of TLQP-21 Activation of a
Binding Site on CHO Cells.
AB - VGF is a propeptide of 617 amino acids expressed throughout the central and the
peripheral nervous system. VGF and peptides derived from its processing have been
found in dense core vesicles and are released from neuronal and neuroendocrine
cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP
21 (VGF556-576) has raised a huge interest and is one of most studied. TLQP-21 is
a multifunctional neuropeptide involved in the control of several physiological
functions, potentially including energy homeostasis, pain modulation, stress
responsiveness and reproduction. Although little information is available about
its receptor and the intracellular mechanisms mediating its biological effects,
recent reports suggest that TLQP-21 may bind to the complement receptors C3aR1
and/or gC1qR. The first aim of this study was to ascertain the existence and
nature of TLQP-21 binding sites in CHO cells. Secondly, we endeavored to
characterize the ligand binding to these sites by using a small panel of VGF
derived peptides. And finally, we investigated the influence of TLQP-21 on
selected intracellular signaling pathways. We report that CHO cells express a
single class of saturable and specific binding sites for TLQP-21 with an affinity
and capacity of Kd = 0.55 +/- 0.05 * 10-9 M and Bmax = 81.7 +/- 3.9 fmol/mg
protein, respectively. Among the many bioactive products derived from the C
terminal region of VGF that we tested, TLQP-21 was the most potent in stimulating
intracellular calcium mobilization in CHO cells; this effect is primarily due to
its C-terminal fragment (HFHH-10). TLQP-21 induced rapid and transient
dephosphorylation of phospholipase Cgamma1 and phospholipase A2. Generation of
IP3 and diacylglycerol was crucial for TLQP-21 bioactivity. In conclusion, our
results suggest that the receptor stimulated by TLQP-21 belongs to the family of
the Gq-coupled receptors, and its activation first increases membrane-lipid
derived second messengers which thereby induce the mobilization of Ca2+ from the
endoplasmic reticulum followed by a slower store-operated Ca2+ entry from outside
the cell.
PMID- 28424620
TI - Relations between Effects and Structure of Small Bicyclic Molecules on the
Complex Model System Saccharomyces cerevisiae.
AB - The development of compounds able to modify biological functions largely took
advantage of parallel synthesis to generate a broad chemical variance of
compounds to be tested for the desired effect(s). The budding yeast Saccharomyces
cerevisiae is a model for pharmacological studies since a long time as it
represents a relatively simple system to explore the relations among chemical
variance and bioactivity. To identify relations between the chemical features of
the molecules and their activity, we delved into the effects of a library of
small compounds on the viability of a set of S. cerevisiae strains. Thanks to the
high degree of chemical diversity of the tested compounds and to the measured
effect on the yeast growth rate, we were able to scale-down the chemical library
and to gain information on the most effective structures at the substituent
level. Our results represent a valuable source for the selection, rational
design, and optimization of bioactive compounds.
PMID- 28424619
TI - Retinal and Circulating miRNAs in Age-Related Macular Degeneration: An In vivo
Animal and Human Study.
AB - Age related macular degeneration (AMD) is the leading cause of blindness among
people aged 50 and over. Retinal deposition of amyloid-beta (Abeta) aggregates in
AMD patients has suggested a potential link between AMD and Alzheimer's disease
(AD). We have evaluated the differential retinal expression profile of miRNAs in
a rat model of AMD elicited by Abeta. A serum profile of miRNAs in AMD patients
has been also assessed using single TaqMan assay. Analysis of retina from rats
intravitreally injected with Abeta revealed that miR-27a, miR-146a, and miR-155
were up-regulated in comparison to control rats. Seven miRNA (miR-9, miR-23a, miR
27a, miR-34a, miR-126, miR-146a, and miR-155) have been found to be dysregulated
in serum of AMD patients in comparison to control group. Analysis of pathways has
revealed that dysregulated miRNAs, both in the AMD animal model and in AMD
patients, can target genes regulating pathways linked to neurodegeneration and
inflammation, reinforcing the hypothesis that AMD is a protein misfolding disease
similar to AD. In fact, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have
been found to be dysregulated both in AMD and AD. In conclusion, we suggest that
miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 represent potential
biomarkers and new pharmacological targets for AMD.
PMID- 28424621
TI - Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in
Cisplatin-induced Acute Kidney Injury.
AB - Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle
(Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and
antitumor properties. Here, we showed that silybin protected against cisplatin
induced acute kidney injury (AKI) by improving mitochondrial function through the
regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO)
mice were administered a single intraperitoneal (i.p.) injection of cisplatin
with or without treatment with silybin. Moreover, cultured HK2 cells were used to
evaluate mitochondrial morphology and function. Our data suggested that silybin
enhanced SIRT3 expression after cisplatin administration both in vivo and in
vitro. Silybin treatment improved mitochondrial function and bioenergetics in
wild-type, but not SIRT3-defective, cells and mice. Moreover, we demonstrated
that silybin markedly attenuated cisplatin-induced AKI and tubular cell apoptosis
and improved cell regeneration in a SIRT3-dependent manner. Collectively, these
results suggest that silybin is a pharmacological activator of SIRT3 capable of
protecting against cisplatin-induced tubular cell apoptosis and AKI by improving
mitochondrial function. Thus, silybin could serve as a potential clinical
renoprotective adjuvant treatment in cisplatin chemotherapy.
PMID- 28424622
TI - Pravastatin Chronic Treatment Sensitizes Hypercholesterolemic Mice Muscle to
Mitochondrial Permeability Transition: Protection by Creatine or Coenzyme Q10.
AB - Statins are efficient cholesterol-lowering medicines utilized worldwide. However,
10% of patients suffer from adverse effects specially related to skeletal muscle
function. Pro- or anti-oxidant effects of statins have been reported. Here we
hypothesized that statins induce muscle mitochondrial oxidative stress leading to
mitochondrial permeability transition (MPT) which may explain statin muscle
toxicity. Thus, our aims were to investigate the effects of statin chronic
treatment on muscle mitochondrial respiration rates, MPT and redox state
indicators in the context of hypercholesterolemia. For this purpose, we studied
muscle biopsies of the hypercholesterolemic LDL receptor knockout mice (LDLr-/-)
treated with pravastatin during 3 months. Plantaris, but not soleus muscle of
treated mice showed significant inhibition of respiration rates induced by ADP (
14%), oligomycin (-20%) or FCCP (-40%). Inhibitions of respiratory rates were
sensitive to EGTA (Ca2+ chelator), cyclosporin A (MPT inhibitor), ruthenium red
(inhibitor of mitochondria Ca2+ uptake) and coenzyme Q10 (antioxidant),
indicating that pravastatin treatment favors Ca2+ induced MPT. Diet
supplementation with creatine (antioxidant) also protected treated mice against
pravastatin sensitization to Ca2+ induced MPT. Among several antioxidant enzymes
analyzed, only catalase activity was increased by 30% in plantaris muscle of
pravastatin treated mice. Oxidized lipids, but not proteins biomarkers were
identified in treated LDLr-/- plantaris muscle. Taken together, the present
results suggest that chronic pravastatin administration to a model of familial
hypercholesterolemia promotes mitochondrial dysfunctions in plantaris muscle that
can be counteracted by antioxidants administered either in vitro (CoQ10) or in
vivo (creatine). Therefore, we propose that inhibition of muscle mitochondrial
respiration by pravastatin leads to an oxidative stress that, in the presence of
calcium, opens the permeability transition pore. This mitochondrial oxidative
stress caused by statin treatment also signals for cellular antioxidant system
responses such as catalase upregulation. These results suggest that the
detrimental effects of statins on muscle mitochondria could be prevented by co
administration of a safe antioxidant such as creatine or CoQ10.
PMID- 28424623
TI - Notch Signaling in Ischemic Damage and Fibrosis: Evidence and Clues from the
Heart.
AB - Notch signaling is a major intercellular coordination mechanism highly conserved
throughout evolution. In vertebrates, Notch signaling is physiologically involved
in embryo development, including mesenchymal cell commitment, formation of heart
tissues and angiogenesis. In post-natal life, Notch signaling is maintained as a
key mechanism of cell-cell communication and its dysregulations have been found
in pathological conditions such as ischemic and fibrotic diseases. In the heart,
Notch takes part in the protective response to ischemia, being involved in pre-
and post-conditioning, reduction of reperfusion-induced oxidative stress and
myocardial damage, and cardiomyogenesis. Conceivably, the cardioprotective
effects of Notch may depend on neo-angiogenesis, thus blunting lethal myocardial
ischemia, as well as on direct stimulation of cardiac cells to increase their
resistance to injury. Another post-developmental adaptation of Notch signaling is
fibrosis: being involved in the orientation of mesenchymal cell fate, Notch can
modulate the differentiation of pro-fibrotic myofibroblasts, e.g., by reducing
the effects of the profibrotic cytokine TGF-beta. In conclusion, Notch can
regulate the interactions between heart muscle and stromal cells and switch
cardiac repair from a pro-fibrotic default pathway to a pro-cardiogenic one.
These features make Notch signaling a suitable target for new cardiotropic
therapies.
PMID- 28424624
TI - Commentary: A BK (Slo1) channel journey from molecule to physiology.
PMID- 28424626
TI - A Rat Immobilization Model Based on Cage Volume Reduction: A Physiological Model
for Bed Rest?
AB - Bed rest has been an established treatment in the past prescribed for critically
illness or convalescing patients, in order to preserve their body metabolic
resource, to prevent serious complications and to support their rapid path to
recovery. However, it has been reported that prolonged bed rest can have
detrimental consequences that may delay or prevent the recovery from clinical
illness. In order to study disuse-induced changes in muscle and bone, as observed
during prolonged bed rest in humans, an innovative new model of muscle disuse for
rodents is presented. Basically, the animals are confined to a reduced space
designed to restrict their locomotion movements and allow them to drink and eat
easily, without generating physical stress. The animals were immobilized for
either 7, 14, or 28 days. The immobilization procedure induced a significant
decrease of food intake, both at 14 and 28 days of immobilization. The reduced
food intake was not a consequence of a stress condition induced by the model
since plasma corticosterone levels -an indicator of a stress response- were not
altered following the immobilization period. The animals showed a significant
decrease in soleus muscle mass, grip force and cross-sectional area (a measure of
fiber size), together with a decrease in bone mineral density. The present model
may potentially serve to investigate the effects of bed-rest in pathological
states characterized by a catabolic condition, such as diabetes or cancer.
PMID- 28424627
TI - Blood Pressure Increase during Oxygen Supplementation in Chronic Kidney Disease
Patients Is Mediated by Vasoconstriction Independent of Baroreflex Function.
AB - Renal hypoxia is thought to be an important pathophysiological factor in the
progression of chronic kidney disease (CKD) and the associated hypertension. In a
previous study among CKD patients, supplementation with 100% oxygen reduced
sympathetic nerve activity (SNA) and lowered blood pressure (BP). We aimed to
assess the underlying haemodynamic modulation and hypothesized a decreased
systemic vascular resistance (SVR). To that end, 19 CKD patients were studied
during 15-min intervals of increasing partial oxygen pressure (ppO2) from room
air (0.21 ATA) to 1.0 ATA and further up to 2.4 ATA, while continuously measuring
finger arterial blood pressure (Finapres). Off-line, we derived indexes of SVR,
cardiac output (CO) and baroreflex sensitivity from the continuous BP recordings
(Modelflow). During oxygen supplementation, systolic, and diastolic BP both
increased dose-dependently from 128 +/- 24 and 72 +/- 19 mmHg respectively at
baseline to 141 +/- 23 (p < 0.001) and 80 +/- 21 mmHg (p < 0.001) at 1.0 ATA
oxygen. Comparing baseline and 1.0 ATA oxygen, SVR increased from 1440 +/- 546 to
1745 +/- 710 dyn.s/cm5 (p = 0.009), heart rate decreased from 60 +/- 8 to 58 +/-
6 bpm (p < 0.001) and CO from 5.0 +/- 1.3 to 4.6 +/- 1.1 L/min (p = 0.02).
Baroreflex sensitivity remained unchanged (13 +/- 13 to 15 +/- 12 ms/mmHg). These
blood pressure effects were absent in a negative control group of eight young
healthy subjects. We conclude that oxygen supplementation in CKD patients causes
a non-baroreflex mediated increased in SVR and blood pressure.
PMID- 28424625
TI - Role of Mitochondrial Retrograde Pathway in Regulating Ethanol-Inducible
Filamentous Growth in Yeast.
AB - In yeast, ethanol is produced as a by-product of fermentation through glycolysis.
Ethanol also stimulates a developmental foraging response called filamentous
growth and is thought to act as a quorum-sensing molecule. Ethanol-inducible
filamentous growth was examined in a small collection of wine/European strains,
which validated ethanol as an inducer of filamentous growth. Wine strains also
showed variability in their filamentation responses, which illustrates the
striking phenotypic differences that can occur among individuals. Ethanol
inducible filamentous growth in Sigma1278b strains was independent of several of
the major filamentation regulatory pathways [including fMAPK, RAS-cAMP, Snf1,
Rpd3(L), and Rim101] but required the mitochondrial retrograde (RTG) pathway, an
inter-organellar signaling pathway that controls the nuclear response to defects
in mitochondrial function. The RTG pathway regulated ethanol-dependent
filamentous growth by maintaining flux through the TCA cycle. The ethanol
dependent invasive growth response required the polarisome and transcriptional
induction of the cell adhesion molecule Flo11p. Our results validate established
stimuli that trigger filamentous growth and show how stimuli can trigger highly
specific responses among individuals. Our results also connect an inter
organellar pathway to a quorum sensing response in fungi.
PMID- 28424628
TI - Branchial Pathomorphology of Southern Bluefin Tuna Thunnus maccoyii (Castelnau,
1872) Infected by Helminth and Copepodan Parasites.
AB - Three metazoan parasites, a monogenean Hexostoma thynni and two species of
copepods Pseudocycnus appendiculatus and Euryphorus brachypterus are known to
parasitize the gills of ranched southern bluefin tuna (SBT) and other tuna
species. However, there is no detailed information describing the pathological
response to infection by these parasites in this species. Wild southern bluefin
tuna Thunnus maccoyii (approximately 3 years of age), captured and towed to a
grow-out site in the waters immediately south of Port Lincoln, South Australia
were subsequently sampled (n = 10) monthly from March until August 2004 during
commercial harvest operations. Longitudinal sections of gill hemibranchs with
attached parasites were excised and fixed for routine histology and
immunohistochemistry. Reference samples were also collected from fish displaying
no signs of parasitism or other grossly observable anomalies. Two morphologically
distinct granulocytes were observed and putatively identified as eosinophils and
mast cells. Pathology was localized to filaments upon and immediately adjacent to
parasite attachment sites. Branchial cellular responses, adjunct to the
attachment of H. thynni by its opisthaptoral clamps, included hyperplasia and
inflammation resulting in structural remodeling of branchial tissues.
Inflammatory infiltrates were often dominated by putative eosinophils and
lymphocytes when parasitized by H. thynni and P. appendiculatus. Gill associated
lymphoid tissue infiltrated the lamellar regions particularly in response to
helminth infection. A variable response ranging from hemorrhage with minor
hyperplasia or fibroplasia and eosinophilic inflammation to a barely discernible
change was seen for gill sections harboring P. appendiculatus and E.
brachypterus. The magnitude of the host response to attachment by the latter was
congruent with attachment proximity and parasite load. On the basis of the host
responses reported here and the low intensity of infection observed in other
associated studies these gill ectoparasites are currently considered a low risk
for wild and ranched adult SBT.
PMID- 28424630
TI - Hippo Pathway and Skeletal Muscle Mass Regulation in Mammals: A Controversial
Relationship.
AB - Skeletal muscle mass reflects a dynamic turnover between net protein synthesis
and degradation. In addition, satellite cell inclusion may contribute to increase
muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a
few studies looked at the involvement of the newly discovered Hippo pathway in
the regulation of muscle mass. In line with its roles in other organs, it has
been hypothesized that the Hippo pathway could play a role in different
regulatory mechanisms in skeletal muscle as well, namely proliferation and
renewal of satellite cells, differentiation, death, and growth of myogenic cells.
While the Hippo components have been identified in skeletal muscle, their role in
muscle mass regulation has been less investigated and conflicting results have
been reported. Indeed, the first studies described both atrophic and hypertrophic
roles of the Hippo pathway and its effectors Yap/Taz using different biochemical
approaches. Further, investigation is therefore warranted to determine the role
of the Hippo pathway in the regulation of skeletal muscle mass. New components of
the pathway will probably emerge and unsuspected roles will likely be discovered
due to its numerous interactions with different cellular processes. This mini
review aims to summarize the current literature concerning the roles of the Hippo
pathway in the regulation of muscle mass and to develop the hypothesis that this
pathway could contribute to muscle mass adaptation after exercise.
PMID- 28424629
TI - Molecular and Cellular Mechanisms of Apoptosis during Dissociated
Spermatogenesis.
AB - Apoptosis is a tightly controlled process by which tissues eliminate unwanted
cells. Spontaneous germ cell apoptosis in testis has been broadly investigated in
mammals that have an associated spermatogenesis pattern. However, the mechanism
of germ cell apoptosis in seasonally breeding reptiles following a dissociated
spermatogenesis has remained enigmatic. In the present study, morphological
evidence has clearly confirmed the dissociated spermatogenesis pattern in
Pelodiscus sinensis. TUNEL and TEM analyses presented dynamic changes and
ultrastructural characteristics of apoptotic germ cells during seasonal
spermatogenesis, implying that apoptosis might be one of the key mechanisms to
clear degraded germ cells. Furthermore, using RNA-Seq and digital gene expression
(DGE) profiling, a large number of apoptosis-related differentially expressed
genes (DEGs) at different phases of spermatogenesis were identified and
characterized in the testis. DGE and RT-qPCR analysis revealed that the critical
anti-apoptosis genes, such as Bcl-2, BAG1, and BAG5, showed up-regulated patterns
during intermediate and late spermatogenesis. Moreover, the increases in
mitochondrial transmembrane potential in July and October were detected by JC-1
staining. Notably, the low protein levels of pro-apoptotic cleaved caspase-3 and
CytC in cytoplasm were detected by immunohistochemistry and western blot
analyses, indicating that the CytC-Caspase model might be responsible for the
effects of germ cell apoptosis on seasonal spermatogenesis. These results
facilitate understanding the regulatory mechanisms of apoptosis during
spermatogenesis and uncovering the biological process of the dissociated
spermatogenesis system in reptiles.
PMID- 28424631
TI - Mechanisms Underlying the Emergence of Post-acidosis Arrhythmia at the Tissue
Level: A Theoretical Study.
AB - Acidosis has complex electrophysiological effects, which are associated with a
high recurrence of ventricular arrhythmias. Through multi-scale cardiac computer
modeling, this study investigated the mechanisms underlying the emergence of post
acidosis arrhythmia at the tissue level. In simulations, ten Tusscher-Panfilov
ventricular model was modified to incorporate various data on acidosis-induced
alterations of cellular electrophysiology and intercellular electrical coupling.
The single cell models were incorporated into multicellular one-dimensional (1D)
fiber and 2D sheet tissue models. Electrophysiological effects were quantified as
changes of action potential profile, sink-source interactions of fiber tissue,
and the vulnerability of tissue to the genesis of unidirectional conduction that
led to initiation of re-entry. It was shown that acidosis-induced sarcoplasmic
reticulum (SR) calcium load contributed to delayed afterdepolarizations (DADs) in
single cells. These DADs may be synchronized to overcome the source-sink mismatch
arising from intercellular electrotonic coupling, and produce a premature
ventricular complex (PVC) at the tissue level. The PVC conduction can be
unidirectionally blocked in the transmural ventricular wall with altered
electrical heterogeneity, resulting in the genesis of re-entry. In conclusion,
altered source-sink interactions and electrical heterogeneity due to acidosis
induced cellular electrophysiological alterations may increase susceptibility to
post-acidosis ventricular arrhythmias.
PMID- 28424632
TI - Pro-angiogenic Role of Insulin: From Physiology to Pathology.
AB - The underlying molecular mechanisms involve in the regulation of the angiogenic
process by insulin are not well understood. In this review article, we aim to
describe the role of insulin and insulin receptor activation on the control of
angiogenesis and how these mechanisms can be deregulated in human diseases.
Functional expression of insulin receptors and their signaling pathways has been
described on endothelial cells and pericytes, both of the main cells involved in
vessel formation and maturation. Consequently, insulin has been shown to regulate
endothelial cell migration, proliferation, and in vitro tubular structure
formation through binding to its receptors and activation of intracellular
phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is
potentiated by generation of vascular growth factors, such as the vascular
endothelial growth factor, produced by endothelial cells. Additionally, diseases
such as insulin resistance, obesity, diabetes, and cancer may be associated with
the deregulation of insulin-mediated angiogenesis. Despite this knowledge, the
underlying molecular mechanisms need to be elucidated in order to provide new
insights into the role of insulin on angiogenesis.
PMID- 28424633
TI - Psychopathological Aspects in Childhood Hematopoietic Stem Cell Transplantation
(HSCT): The Perception of Parents and Adolescents.
AB - Background: Data about psychosocial sequelae of childhood Hematopoietic Stem Cell
Transplantation (HSCT) are limited and the association with a specific donor type
or other medical factors is largely unknown (Chang et al., 2012). The aim of the
present study was to compare the psychological aspects of pediatric HSCT
survivors with healthy peers. A secondary aim was to detect whether parents and
children differed in the perception of mental health status. The influence of
medical factors on psychological status was also examined. Method: Thirty seven
HSCT survivors (23 males) with a mean age of 14.4 years (SD = 3.03; range 8.16
18.33) were recruited. Twenty-six patients underwent an allogenic HSCT (matched
unrelated donor, n = 20; matched sibling donor, n = 6) and 11 patients received
an autologous HSCT. The children psychological aspects were assessed using the
Youth Self Report (YSR) (Achenbach and Rescorla, 2001) and compared to a group of
matched healthy peers. At the same time, parents were requested to complete the
Child Behavior Checklist 6-18 (Achenbach and Rescorla, 2001). Medical and socio
demographic data were also collected. Results: HSCT survivors reported
significantly higher levels of somatic complains (t27 = 3.14; p = 0.004; mean =
3.1) when compared to healthy peers (mean = 1.5). The parent CBCL scores on
"child total competence" exceeded the normative clinical cutoff in 48.6% cases.
Inter-rater agreement between parent and patient reports was present only in
three scales: total competence score (K = 0.06, p = 0.002), somatic complaints (K
= 0.21, p = 0.003) and attention problems (k = 0.13; p = 0.02). According to
Ancova models, internalizing problems were more frequent in HSCT from family
donors (F2 = 3.13; p = 0.06) or in the presence of acute complications (F1 =
11.95; p = 0.003). Conclusion: In contrast to the perception of parents,
pediatric HSCT survivors reported good psychological health. However, they
complained about more somatic problems as compared with healthy peers. Medical
aspects such as donor source and the presence of acute complications should be
taken into consideration for the psychological approach in order to improve
pediatric HSCT survivor care.
PMID- 28424634
TI - When the Second Language Takes the Lead: Neurocognitive Processing Changes in the
First Language of Adult Attriters.
AB - Although research on multilingualism has revealed continued neuroplasticity for
language-learning beyond what was previously expected, it remains controversial
whether and to what extent a second language (L2) acquired in adulthood may
induce changes in the neurocognitive processing of a first language (L1). First
language (L1) attrition in adulthood offers new insight on neuroplasticity and
the factors that modulate neurocognitive responses to language. To date,
investigations of the neurocognitive correlates of L1 attrition and of factors
influencing these mechanisms are still scarce. Moreover, most event-related
potential (ERP) studies of second language processing have focused on L1
influence on the L2, while cross-linguistic influence in the reverse direction
has been underexplored. Using ERPs, we examined the real-time processing of
Italian relative-clauses in 24 Italian-English adult migrants with predominant
use of English since immigration and reporting attrition of their native-Italian
(Attriters), compared to 30 non-attriting monolinguals in Italy (Controls). Our
results showed that Attriters differed from Controls in their acceptability
judgment ratings and ERP responses when relative clause constructions were
ungrammatical in English, though grammatical in Italian. Controls' ERP responses
to unpreferred sentence constructions were consistent with garden path effects
typically observed in the literature for these complex sentences. In contrast,
due to L2-English influence, Attriters were less sensitive to semantic cues than
to word-order preferences, and processed permissible Italian sentences as
outright morphosyntactic violations. Key factors modulating processing
differences within Attriters were the degree of maintained L1 exposure, length of
residence in the L2 environment and L2 proficiency - with higher levels of L2
immersion and proficiency associated with increased L2 influence on the L1. To
our knowledge, this is the first demonstration that high levels of L2 proficiency
and exposure may render a grammatical sentence in one's native language
ungrammatical. These group differences strongly point to distinct processing
strategies and provide evidence that even a "stabilized" L1 grammar is subject to
change after a prolonged period of L2 immersion and reduced L1 use, especially in
linguistic areas promoting cross-linguistic influence.
PMID- 28424635
TI - Preferential Processing of Social Features and Their Interplay with Physical
Saliency in Complex Naturalistic Scenes.
AB - According to so-called saliency-based attention models, attention during free
viewing of visual scenes is particularly allocated to physically salient image
regions. In the present study, we assumed that social features in complex
naturalistic scenes would be processed preferentially irrespective of their
physical saliency. Therefore, we expected worse prediction of gazing behavior by
saliency-based attention models when social information is present in the visual
field. To test this hypothesis, participants freely viewed color photographs of
complex naturalistic social (e.g., including heads, bodies) and non-social (e.g.,
including landscapes, objects) scenes while their eye movements were recorded. In
agreement with our hypothesis, we found that social features (especially heads)
were heavily prioritized during visual exploration. Correspondingly, the presence
of social information weakened the influence of low-level saliency on gazing
behavior. Importantly, this pattern was most pronounced for the earliest
fixations indicating automatic attentional processes. These findings were further
corroborated by a linear mixed model approach showing that social features
(especially heads) add substantially to the prediction of fixations beyond
physical saliency. Taken together, the current study indicates gazing behavior
for naturalistic scenes to be better predicted by the interplay of social and
physically salient features than by low-level saliency alone. These findings
strongly challenge the generalizability of saliency-based attention models and
demonstrate the importance of considering social influences when investigating
the driving factors of human visual attention.
PMID- 28424637
TI - Listening Niches across a Century of Popular Music.
AB - This article investigates the contexts, or "listening niches", in which people
hear popular music. The study spanned a century of popular music, divided into 10
decades, with participants born between 1940 and 1999. It asks about whether they
know and like the music in each decade, and their emotional reactions. It also
asks whether the music is associated with personal memories and, if so, with whom
they were listening, or whether they were listening alone. Finally, it asks what
styles of music they were listening to, and the music media they were listening
with, in different periods of their lives. The results show a regular progression
through the life span of listening with different individuals (from parents to
children) and with different media (from records to streaming services). A number
of effects found in previous studies were replicated, but the study also showed
differences across the birth cohorts. Overall, there was a song specific age
effect with preferences for music of late adolescence and early adulthood;
however, this effect was stronger for the older participants. In general, music
of the 1940s, 1960s, and 1980s was preferred, particularly among younger
participants. Music of these decades also produced the strongest emotional
responses, and the most frequent and specific personal memories. When growing up,
the participants tended to listen to the older music on the older media, but
rapidly shifted to the new music technologies in their late teens and early 20s.
Younger listeners are currently listening less to music alone than older
listeners, suggesting an important role of socially sharing music, but they also
report feeling sadder when listening to music. Finally, the oldest listeners had
the broadest taste, liking music that they had been exposed to during their
lifetimes in different listening niches.
PMID- 28424636
TI - The Neural Basis of Speech Perception through Lipreading and Manual Cues:
Evidence from Deaf Native Users of Cued Speech.
AB - We present here the first neuroimaging data for perception of Cued Speech (CS) by
deaf adults who are native users of CS. CS is a visual mode of communicating a
spoken language through a set of manual cues which accompany lipreading and
disambiguate it. With CS, sublexical units of the oral language are conveyed
clearly and completely through the visual modality without requiring hearing. The
comparison of neural processing of CS in deaf individuals with processing of
audiovisual (AV) speech in normally hearing individuals represents a unique
opportunity to explore the similarities and differences in neural processing of
an oral language delivered in a visuo-manual vs. an AV modality. The study
included deaf adult participants who were early CS users and native hearing users
of French who process speech audiovisually. Words were presented in an event
related fMRI design. Three conditions were presented to each group of
participants. The deaf participants saw CS words (manual + lipread), words
presented as manual cues alone, and words presented to be lipread without manual
cues. The hearing group saw AV spoken words, audio-alone and lipread-alone. Three
findings are highlighted. First, the middle and superior temporal gyrus
(excluding Heschl's gyrus) and left inferior frontal gyrus pars triangularis
constituted a common, amodal neural basis for AV and CS perception. Second,
integration was inferred in posterior parts of superior temporal sulcus for audio
and lipread information in AV speech, but in the occipito-temporal junction,
including MT/V5, for the manual cues and lipreading in CS. Third, the perception
of manual cues showed a much greater overlap with the regions activated by CS
(manual + lipreading) than lipreading alone did. This supports the notion that
manual cues play a larger role than lipreading for CS processing. The present
study contributes to a better understanding of the role of manual cues as support
of visual speech perception in the framework of the multimodal nature of human
communication.
PMID- 28424638
TI - The Acquisition of Orthographic Knowledge: Evidence from the Lexicality Effects
on N400.
AB - This study aimed to understand how reading ability shapes the lexicality effects
on N400. Fifty-three typical developing children from the second to the sixth
grades were asked to perform the pronounceability judgment task on a set of
Chinese real characters (RC), pseudocharacters (PC) and non-characters (NC), as
ERPs were recorded. The cluster-based permutation analysis revealed that children
with low- to medium-reading ability showed greater negativity to NCs than to RCs
and PCs in frontal sites from 300 to 450 ms, while children with high ability
group showed a greater positivity to NCs than both RCs and PCs at central to
posterior sites. Furthermore, the linear mixed model (LMM) analysis was applied
to investigate the relationship between lexicality effects on N400 and reading
related behavioral assessments on a set of standardized tests (including
character recognition, vocabulary size, phonological awareness, and working
memory). The results found that in children with lower reading ability, the N400
elicited by NCs becomes more negative in the frontal sites. For children with
higher reading ability, the N400 elicited by NCs became more positive than that
elicited by RCs or PCs in the posterior sites. These findings demonstrate the
developmental changes in the lexicality effects on N400 as children become more
advanced readers and suggested that the lexicality effects on N400 can serve as
neural markers for the evaluation of orthographic proficiency in reading
development.
PMID- 28424640
TI - Redefining Critical Thinking: Teaching Students to Think like Scientists.
PMID- 28424639
TI - Inconsistent Effect of Arousal on Early Auditory Perception.
AB - Mood has been shown to influence cognitive performance. However, little is known
about the influence of mood on sensory processing, specifically in the auditory
domain. With the current study, we sought to investigate how auditory processing
of neutral sounds is affected by the mood state of the listener. This was tested
in two experiments by measuring masked-auditory detection thresholds before and
after a standard mood-induction procedure. In the first experiment (N = 76), mood
was induced by imagining a mood-appropriate event combined with listening to mood
inducing music. In the second experiment (N = 80), imagining was combined with
affective picture viewing to exclude any possibility of confounding the results
by acoustic properties of the music. In both experiments, the thresholds were
determined by means of an adaptive staircase tracking method in a two-interval
forced-choice task. Masked detection thresholds were compared between
participants in four different moods (calm, happy, sad, and anxious), which
enabled differentiation of mood effects along the dimensions arousal and
pleasure. Results of the two experiments were analyzed both in separate analyses
and in a combined analysis. The first experiment showed that, while there was no
impact of pleasure level on the masked threshold, lower arousal was associated
with lower threshold (higher masked sensitivity). However, as indicated by an
interaction effect between experiment and arousal, arousal did have a different
effect on the threshold in Experiment 2. Experiment 2 showed a trend of arousal
in opposite direction. These results show that the effect of arousal on auditory
masked sensitivity may depend on the modality of the mood-inducing stimuli. As
clear conclusions regarding the genuineness of the arousal effect on the masked
threshold cannot be drawn, suggestions for further research that could clarify
this issue are provided.
PMID- 28424641
TI - Are Individuals Luck Egalitarians? - An Experiment on the Influence of Brute and
Option Luck on Social Preferences.
AB - According to luck egalitarianism, inequalities should be deemed fair as long as
they follow from individuals' deliberate and fully informed choices (i.e., option
luck) while inequalities should be deemed unfair if they follow from choices over
which the individual has no control (i.e., brute luck). This study investigates
if individuals' fairness preferences correspond with the luck egalitarian
fairness position. More specifically, in a laboratory experiment we test how
individuals choose to redistribute gains and losses that stem from option luck
compared to brute luck. A two-stage experimental design with real incentives was
employed. We show that individuals (n = 226) change their action associated with
re-allocation depending on the underlying conception of luck. Subjects in the
brute luck treatment equalized outcomes to larger extent (p = 0.0069). Thus,
subjects redistributed a larger amount to unlucky losers and a smaller amount to
lucky winners compared to equivalent choices made in the option luck treatment.
The effect is less pronounced when conducting the experiment with third-party
dictators, indicating that there is some self-serving bias at play. We conclude
that people have fairness preference not just for outcomes, but also for how
those outcomes are reached. Our findings are potentially important for
understanding the role citizens assign individual responsibility for life
outcomes, i.e., health and wealth.
PMID- 28424642
TI - Response: Commentary: Incubation and Intuition in Creative Problem Solving.
PMID- 28424643
TI - Oral Storytelling as Evidence of Pedagogy in Forager Societies.
AB - Teaching is reportedly rare in hunter-gatherer societies, raising the question of
whether it is a species-typical trait in humans. A problem with past studies is
that they tend to conceptualize teaching in terms of Western pedagogical
practices. In contrast, this study proceeds from the premise that teaching
requires the ostensive manifestation of generalizable knowledge: the teacher must
signal intent to share information, indicate the intended recipient, and transmit
knowledge that is applicable beyond the present context. Certain features of
human communication appear to be ostensive in function (e.g., eye contact,
pointing, contingency, prosodic variation), and collectively serve as "natural
pedagogy." Tellingly, oral storytelling in forager societies typically employs
these and other ostensive behaviors, and is widely reported to be an important
source of generalizable ecological and social knowledge. Despite this, oral
storytelling has been conspicuously overlooked in studies of teaching in
preliterate societies. Accordingly, this study presents evidence that oral
storytelling involves the use of ostension and the transmission of generic
knowledge, thereby meeting the criteria of pedagogy.
PMID- 28424644
TI - The Association between Parenting Behavior and Executive Functioning in Children
and Young Adolescents.
AB - Executive functioning (EF) is associated with various aspects of school
achievement and cognitive development in children and adolescents. There has been
substantial research investigating associations between EF and other factors in
young children, such as support processes and parenting, but less research has
been conducted about external factors relating to EF in older children and
adolescents. Therefore, the present study investigates one possible factor that
could correlate with EF in school-age children and adolescents: parenting
behavior. The cross-sectional study design gathered data from 169 children in
primary schools, middle-schools, and Gymnasien, and their corresponding parents.
All children underwent a standardized task to measure EF, the computer-based
Erikson Flanker task, which evaluates EF as a function of error rates and
response time. A self-report questionnaire was used to assess parenting behavior.
Multilevel analysis was implemented to test the effects of parenting behavior on
EF in school-age children. The results show significant associations between
various parenting behaviors and children's EF: High scores on parental
involvement or parental responsibility are associated with low error rates on the
Erikson Flanker task, whereas high parental scores on inconsistent discipline are
associated with high error rates. These correlations between parenting behavior
and EF remained significant despite controlling for child age, maternal
education, family income, and baseline performance (i.e., congruent trials on the
Erikson Flanker task). No associations were found between parental behavior and
reaction time on the Erikson Flanker task. These results indicate the important
association between parenting behaviors and EF skills in school-age children, and
foster the necessity to inform parents about ways in which they can optimally
support their children's cognitive development.
PMID- 28424645
TI - Cerebellar tDCS Does Not Enhance Performance in an Implicit Categorization
Learning Task.
AB - Background: Transcranial Direct Current Stimulation (tDCS) is a form of non
invasive electrical stimulation that changes neuronal excitability in a polarity
and site-specific manner. In cognitive tasks related to prefrontal and cerebellar
learning, cortical tDCS arguably facilitates learning, but the few studies
investigating cerebellar tDCS, however, are inconsistent. Objective: We
investigate the effect of cerebellar tDCS on performance of an implicit
categorization learning task. Methods: Forty participants performed a
computerized version of an implicit categorization learning task where squares
had to be sorted into two categories, according to an unknown but fixed rule that
integrated both the size and luminance of the square. Participants did one round
of categorization to familiarize themselves with the task and to provide a
baseline of performance. After that, 20 participants received anodal tDCS (20
min, 1.5 mA) over the right cerebellum, and 19 participants received sham
stimulation and simultaneously started a second session of the categorization
task using a new rule. Results: As expected, subjects performed better in the
second session than in the first, baseline session, showing increased accuracy
scores and reduced reaction times. Over trials, participants learned the
categorization rule, improving their accuracy and reaction times. However, we
observed no effect of anodal tDCS stimulation on overall performance or on
learning, compared to sham stimulation. Conclusion: These results suggest that
cerebellar tDCS does not modulate performance and learning on an implicit
categorization task.
PMID- 28424646
TI - Duration Aftereffect Depends on the Duration of Adaptation.
AB - It has been widely demonstrated that a prolonged adaptation to a relatively long
or short stimulus leads to a robust repulsive duration aftereffect. However,
little is known about the rapid adaptation to stimulus duration. In this study,
we investigated whether the duration aftereffect could also be induced by short
term adaptation to stimuli of both sub- and supra-second durations. To control
for the internal reference for duration judgment, participants were adapted to a
stimulus of medium duration, and then tested with both longer and shorter
stimuli. We found that the duration aftereffect was only observed after long-term
adaptation to stimuli of both sub- and supra-second durations, which suggests
that the exposure time to the adaptor is a fundamental factor in determining the
duration aftereffect. Our findings offer further evidence of the duration
aftereffect, which in this study was dissociated from the anchor effect and high
level aftereffects.
PMID- 28424648
TI - Effects of Outcome Predictability on Human Learning.
PMID- 28424647
TI - Bringing Back the Balance: Domain-General Processes Are Also Important in
Numerical Cognition.
PMID- 28424649
TI - Connections of Grasping and Horizontal Hand Movements with Articulation in Czech
Speakers.
AB - We have recently shown in Finnish speakers that articulation of certain vowels
and consonants has a systematic influence on simultaneous grasp actions as well
as on forward and backward hand movements. Here we studied whether these effects
generalize to another language, namely Czech. We reasoned that if the results
generalized to another language environment, it would suggest that the effects
arise through other processes than language-dependent semantic associations.
Rather, the effects would be likely to arise through language-independent
interactions between processes that plan articulatory gestures and hand
movements. Participants were presented with visual stimuli specifying
articulations to be uttered (e.g., A or I), and they were required to produce a
manual response concurrently with the articulation. In Experiment 1 they
responded with a precision or a power grip, whereas in Experiment 2 they
responded with a forward or a backward hand movement. The grip congruency effect
was fully replicated: the consonant [k] and the vowel [alpha] were associated
with power grip responses, while the consonant [t] and the vowel [i] were
associated with precision grip responses. The forward/backward congruency effect
was replicated with vowels [alpha], [o], which were associated with backward
movement and with [i], which was associated with forward movement, but not with
consonants [k] and [t]. These findings suggest that the congruency effects mostly
reflect interaction between processes that plan articulatory gestures and hand
movements with an exception that the forward/backward congruency effect might
only work with vowel articulation.
PMID- 28424651
TI - Racial Assumptions Color the Mental Representation of Social Class.
AB - We investigated the racial content of perceivers' mental images of different
socioeconomic categories. We selected participants who were either high or low in
prejudice toward the poor. These participants saw 400 pairs of visually noisy
face images. Depending on condition, participants chose the face that looked like
a poor person, a middle income person, or a rich person. We averaged the faces
selected to create composite images of each social class. A second group of
participants rated the stereotypical Blackness of these images. They also rated
the face images on a variety of psychological traits. Participants high in
economic prejudice produced strongly class-differentiated mental images. They
imagined the poor to be Blacker than middle income and wealthy people. They also
imagined them to have less positive psychological characteristics. Participants
low in economic prejudice also possessed images of the wealthy that were
relatively White, but they represented poor and middle class people in a less
racially differentiated way. We discuss implications for understanding the
intersections of race and class in social perception.
PMID- 28424650
TI - The Role of the Left Anterior Temporal Lobe for Unpredictable and Complex
Mappings in Word Reading.
AB - The anterior temporal lobes (ATLs) have been consistently associated with
semantic processing which, in turn, has a key role in reading aloud single words.
This study aimed to investigate (1) the reading abilities in patients with the
semantic variant of primary progressive aphasia (svPPA), and (2) the relationship
between gray matter (GM) volume of the left ATL and word reading performance
using voxel-based morphometry (VBM). Three groups of participants (svPPA,
Alzheimer's Disease, AD and healthy elderly adults) performed a reading task with
exception words, regular words and pseudowords, along with a structural magnetic
resonance imaging scan. For exception words, the svPPA group had a lower accuracy
and a greater number of regularization errors as compared to the control groups
of healthy participants and AD patients. Similarly, for regular words, svPPA
patients had a lower accuracy in comparison with AD patients, and a greater
number of errors related to complex orthography-to-phonology mappings (OPM) in
comparison to both control groups. VBM analyses revealed that GM volume of the
left ATL was associated with the number of regularization errors. Also, GM volume
of the left lateral ATL was associated with the number of errors with complex OPM
during regular word reading. Our results suggest that the left ATL might play a
role in the reading of exception words, in accordance with its role in semantic
processing. Results further support the involvement of the left lateral ATL in
combinatorial processes, including the integration of semantic and phonological
information, for both exception and regular words.
PMID- 28424652
TI - Quantitative Electroencephalographic Biomarkers in Preclinical and Human Studies
of Huntington's Disease: Are They Fit-for-Purpose for Treatment Development?
AB - A major focus in development of novel therapies for Huntington's disease (HD) is
identification of treatments that reduce the burden of mutant huntingtin (mHTT)
protein in the brain. In order to identify and test the efficacy of such
therapies, it is essential to have biomarkers that are sensitive to the effects
of mHTT on brain function to determine whether the intervention has been
effective at preventing toxicity in target brain systems before onset of clinical
symptoms. Ideally, such biomarkers should have a plausible physiologic basis for
detecting the effects of mHTT, be measureable both in preclinical models and
human studies, be practical to measure serially in clinical trials, and be
reliably measurable in HD gene expansion carriers (HDGECs), among other features.
Quantitative electroencephalography (qEEG) fulfills many of these basic criteria
of a "fit-for-purpose" biomarker. qEEG measures brain oscillatory activity that
is regulated by the brain structures that are affected by mHTT in premanifest and
early symptom individuals. The technology is practical to implement in the
laboratory and is well tolerated by humans in clinical trials. The biomarkers are
measureable across animal models and humans, with findings that appear to be
detectable in HDGECs and translate across species. We review here the literature
on recent developments in both preclinical and human studies of the use of qEEG
biomarkers in HD, and the evidence for their usefulness as biomarkers to help
guide development of novel mHTT lowering treatments.
PMID- 28424653
TI - Disentangling Stigma from Functional Neurological Disorders: Conference Report
and Roadmap for the Future.
AB - A multidisciplinary expert review of key issues and future directions from the
conference "Controversial labels and clinical uncertainties: psychogenic
disorders, conversion disorder, and functional symptoms." On October 9 and 10,
2015, a conference entitled "Controversial labels and clinical uncertainties:
psychogenic disorders, conversion disorder, and functional symptoms" was held at
the Center for Ethics, Emory University, Atlanta, GA, USA. This conference
brought together a select group of 30 distinguished thought leaders and
practitioners, including ethicists, researchers, clinicians, humanities scholars,
and advocates to discuss the unique challenges and controversies related to the
diagnosis, treatment, and stigma for patients with what is currently recognized
as functional ("psychogenic") neurological disorders. Our group of experts
explored the conflicts and ethical tensions within health care that must be
addressed in order to advance care for these disorders. What follows is a
reflection on the conversations between conference attendees outlining key
challenges and value conflicts in the diagnosis and treatment of patients with
functional disorders. With this report, we aim to provide a roadmap for reducing
stigma and improving care for functional neurological disorders (FND). A path
forward would involve (1) setting a multifactorial research agenda that equally
prioritized access to effective psychotherapy as well as identification of novel
biomarkers; (2) empowering patients with FND to be heard and to drive changes in
care; and (3) reducing isolation for clinicians by providing formal training and
setting up multidisciplinary care teams and support networks.
PMID- 28424654
TI - Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse.
AB - The autoimmune disease multiple sclerosis (MS) is characterized by relapses in
the majority of patients. A definitive clinical diagnosis of relapse in MS can be
complicated by the presence of an infection or comorbid disorder. In this mini
review, we describe efforts to develop enhanced imaging techniques and biomarker
detection as future tools for relapse validation. There is emerging evidence of
roles for meningeal inflammation, sex hormones, comorbid metabolic or mood
disorders, and a dysregulated immune profile in the manifestation and severity of
relapse. Specific subsets of immune cells likely drive the pathophysiology of
relapse, and identification of a patient's unique immunological signature of
relapse may help guide future diagnosis and treatment. Finally, these studies
highlight the diversity in terms of relapse presentation, immunological
signature, and response in patients with MS, indicating that going forward the
best approach to assessment and treatment of relapse will be multifactorial and
highly personalized.
PMID- 28424656
TI - Empirical Comparison of Diffusion Kurtosis Imaging and Diffusion Basis Spectrum
Imaging Using the Same Acquisition in Healthy Young Adults.
AB - As diffusion tensor imaging gains widespread use, many researchers have been
motivated to go beyond the tensor model and fit more complex diffusion models, to
gain a more complete description of white matter microstructure and associated
pathology. Two such models are diffusion kurtosis imaging (DKI) and diffusion
basis spectrum imaging (DBSI). It is not clear which DKI parameters are most
closely related to DBSI parameters, so in the interest of enabling comparisons
between DKI and DBSI studies, we conducted an empirical survey of the
interrelation of these models in 12 healthy volunteers using the same diffusion
acquisition. We found that mean kurtosis is positively associated with the DBSI
fiber ratio and negatively associated with the hindered ratio. This was primarily
driven by the radial component of kurtosis. The axial component of kurtosis was
strongly and specifically correlated with the restricted ratio. The joint spatial
distributions of DBSI and DKI parameters are tissue-dependent and stable across
healthy individuals. Our contribution is a better understanding of the biological
interpretability of the parameters generated by the two models in healthy
individuals.
PMID- 28424655
TI - Sustained and Transient Vestibular Systems: A Physiological Basis for
Interpreting Vestibular Function.
AB - Otolithic afferents with regular resting discharge respond to gravity or low
frequency linear accelerations, and we term these the static or sustained
otolithic system. However, in the otolithic sense organs, there is anatomical
differentiation across the maculae and corresponding physiological
differentiation. A specialized band of receptors called the striola consists of
mainly type I receptors whose hair bundles are weakly tethered to the overlying
otolithic membrane. The afferent neurons, which form calyx synapses on type I
striolar receptors, have irregular resting discharge and have low thresholds to
high frequency (e.g., 500 Hz) bone-conducted vibration and air-conducted sound.
High-frequency sound and vibration likely causes fluid displacement which
deflects the weakly tethered hair bundles of the very fast type I receptors.
Irregular vestibular afferents show phase locking, similar to cochlear afferents,
up to stimulus frequencies of kilohertz. We term these irregular afferents the
transient system signaling dynamic otolithic stimulation. A 500-Hz vibration
preferentially activates the otolith irregular afferents, since regular afferents
are not activated at intensities used in clinical testing, whereas irregular
afferents have low thresholds. We show how this sustained and transient
distinction applies at the vestibular nuclei. The two systems have differential
responses to vibration and sound, to ototoxic antibiotics, to galvanic
stimulation, and to natural linear acceleration, and such differential
sensitivity allows probing of the two systems. A 500-Hz vibration that
selectively activates irregular otolithic afferents results in stimulus-locked
eye movements in animals and humans. The preparatory myogenic potentials for
these eye movements are measured in the new clinical test of otolith function
ocular vestibular-evoked myogenic potentials. We suggest 500-Hz vibration may
identify the contribution of the transient system to vestibular controlled
responses, such as vestibulo-ocular, vestibulo-spinal, and vestibulo-sympathetic
responses. The prospect of particular treatments targeting one or the other of
the transient or sustained systems is now being realized in the clinic by the use
of intratympanic gentamicin which preferentially attacks type I receptors. We
suggest that it is valuable to view vestibular responses by this sustained
transient distinction.
PMID- 28424657
TI - Magnetic Vestibular Stimulation (MVS) As a Technique for Understanding the Normal
and Diseased Labyrinth.
AB - Humans often experience dizziness and vertigo around strong static magnetic
fields such as those present in an MRI scanner. Recent evidence supports the idea
that this effect is the result of inner ear vestibular stimulation and that the
mechanism is a magnetohydrodynamic force (Lorentz force) that is generated by the
interactions between normal ionic currents in the inner ear endolymph and the
strong static magnetic field of MRI machines. While in the MRI, the Lorentz force
displaces the cupula of the lateral and anterior semicircular canals, as if the
head was rotating with a constant acceleration. If a human subject's eye
movements are recorded when they are in darkness in an MRI machine (i.e., without
fixation), there is a persistent nystagmus that diminishes but does not
completely disappear over time. When the person exits the magnetic field, there
is a transient aftereffect (nystagmus beating in the opposite direction) that
reflects adaptation that occurred in the MRI. This magnetic vestibular
stimulation (MVS) is a useful technique for exploring set-point adaptation, the
process by which the brain adapts to a change in its environment, which in this
case is vestibular imbalance. Here, we review the mechanism of MVS, how MVS
produces a unique stimulus to the labyrinth that allows us to explore set-point
adaptation, and how this technique might apply to the understanding and treatment
of vestibular and other neurological disorders.
PMID- 28424658
TI - beta- and alpha2-Adrenoceptor Control of Vascular Tension and Catecholamine
Release in Female Normotensive and Spontaneously Hypertensive Rats.
AB - As in humans, young, female, spontaneously hypertensive rats (SHR) have a lower
blood pressure than male SHR. In male, normotensive rats (WKY), alpha2- and
beta1+2-adrenoceptors (AR) reciprocally controlled catecholamine release and
vascular smooth muscle tension. This interaction was malfunctioning in male SHR.
The present study analyzed if a favorable shift in the alpha2/beta1+2AR
interaction may represent an antihypertensive protection in females. Female SHR
(early hypertension, 12-14 weeks) and age-matched WKY were infused with tyramine
(15 min) to stimulate norepinephrine (NE) release through the reuptake
transporter, consequently preventing reuptake. Presynaptic control of vesicular
release was therefore reflected as differences in overflow to plasma. The
released NE increased total peripheral vascular resistance (TPR). The results
showed that beta1>2AR facilitated tyramine-stimulated NE release in both strains,
also in the presence of alpha2AR-antagonist (L-659,066). betaAR-antagonist
(atenolol-beta1, ICI-118551-beta2, nadolol-beta1+2) had no effect on the
increased secretion of epinephrine after L-659,066 in WKY, but beta1>2AR
antagonist augmented the L-659,066-induced increase in the secretion of
epinephrine in SHR. Nadolol increased the TPR response to tyramine with a greater
effect in WKY than SHR, whereas beta1or2-selective antagonists did not. One
betaAR-subtype may therefore substitute for the other. When both beta1+2AR were
blocked, alpha2AR-antagonist still reduced the TPR response in WKY but not SHR.
Thus, alpha2/beta1+2AR reciprocally controlled catecholamine release, with a
particular negative beta1AR-influence on alpha2AR-auto-inhibition of epinephrine
secretion in SHR. Moreover, in these female rats, beta1/2AR-independent alpha2AR
mediated vasoconstriction was seen in WKY but not SHR, but beta1/2AR-mediated
vasodilation downregulated adrenergic vasoconstriction, not only in WKY but also
in SHR.
PMID- 28424659
TI - Online Measurement of Microembolic Signal Burden by Transcranial Doppler during
Catheter Ablation for Atrial Fibrillation-Results of a Multicenter Trial.
AB - INTRODUCTION: Left atrial pulmonary vein isolation (PVI) is an accepted treatment
option for patients with symptomatic atrial fibrillation (AF). This procedure can
be complicated by stroke or silent cerebral embolism. Online measurement of
microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for
characterizing thromboembolic burden during PVI. In this prospective multicenter
trial, we investigated the burden, characteristics, and composition of MES during
left atrial catheter ablation using a variety of catheter technologies. MATERIALS
AND METHODS: PVI was performed in a total of 42 patients using the circular
shaped multielectrode pulmonary vein ablation catheter (PVAC) technology in 23,
an irrigated radiofrequency (IRF) in 14, and the cryoballoon (CB) technology in 5
patients. TCD was used to detect the total MES burden and sustained
thromboembolic showers (TESs) of >30 s. During TES, the site of ablation within
the left atrium was registered. MES composition was classified manually into
"solid," "gaseous," or "equivocal" by off-line expert assessment. RESULTS: The
total MES burden was higher when using IRF compared to CB (2,336 +/- 1,654 vs.
593 +/- 231; p = 0.007) and showed a tendency toward a higher burden when using
IRF compared to PVAC (2,336 +/- 1,654 vs. 1,685 +/- 2,255; p = 0.08). TES
occurred more often when using PVAC compared to IRF (1.5 +/- 2 vs. 0.4 +/- 1.3; p
= 0.04) and most frequently when ablation was performed close to the left
superior pulmonary vein (LSPV). Of the MES, 17.004 (23%) were characterized as
definitely solid, 13.204 (18%) as clearly gaseous, and 44.366 (59%) as equivocal.
DISCUSSION: We investigated the burden and characteristics of MES during left
atrial catheter ablation for AF. All ablation techniques applied in this study
generated a relevant number of MES. There was a significant difference in total
MES burden using IRF compared to CB and a tendency toward a higher burden using
IRF compared to PVAC. The highest TES burden was found in the PVAC group,
particularly during ablation close to the LSPV. The composition of thromboembolic
particles was balanced. The impact of MES, TES, and composition of thromboembolic
particles on neurological outcome needs to be evaluated further. (Clinical Trial
Registration: Deutsches Register Klinischer Studien, https://drks-neu.uniklinik
freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003465.
DRKS00003465.).
PMID- 28424660
TI - CCL2/Monocyte Chemoattractant Protein 1 and Parathyroid Hormone Action on Bone.
AB - Chemokines are small molecules that play a crucial role as chemoattractants for
several cell types, and their components are associated with host immune
responses and repair mechanisms. Chemokines selectively recruit monocytes,
neutrophils, and lymphocytes and induce chemotaxis through the activation of G
protein-coupled receptors. Two well-described chemokine families (CXC and CC) are
known to regulate the localization and trafficking of immune cells in cases of
injury, infection, and tumors. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is
one of the important chemokines from the CC family that controls migration and
infiltration of monocytes/macrophages during inflammation. CCL2 is profoundly
expressed in osteoporotic bone and prostate cancer-induced bone resorption. CCL2
also regulates physiological bone remodeling in response to hormonal and
mechanical stimuli. Parathyroid hormone (PTH) has multifaceted effects on bone,
depending on the mode of administration. Intermittent PTH increases bone in vivo
by increasing the number and activity of osteoblasts, whereas a continuous
infusion of PTH decreases bone mass by stimulating a net increase in bone
resorption. CCL2 is essential for both anabolic and catabolic effects of PTH. In
this review, we will discuss the pharmacological role of PTH and involvement of
CCL2 in the processes of PTH-mediated bone remodeling.
PMID- 28424661
TI - Gonadotropin-Inhibitory Hormone Plays Roles in Stress-Induced Reproductive
Dysfunction.
AB - Physical and psychological stressors suppress hypothalamic-pituitary-gonadal axis
activity and sexual behavior and consequently induce reproductive dysfunction.
Recently, it has been shown that gonadotropin-inhibitory hormone (GnIH), also
called RFamide-related peptide 3 (RFRP) in mammals, which is a potent inhibitory
regulator of gonadotropin-releasing hormone (GnRH) and gonadotropin, is involved
in stress-induced reproductive dysfunction. GnIH/Rfrp (the gene coding RFRP-3)
expression and activity are increased by psychological and immune stress, and
this alteration suppresses GnRH and gonadotropin secretion. Glucocorticoid acts
as a mediator that interacts between stress and hypothalamic GnIH/RFRP-3.
GnIH/RFRP-3 also plays important roles in stress-induced suppression of sexual
behavior and infertility, and genetic silencing of GnIH/Rfrp completely recovers
sexual behavior and fertility. This review summarizes what is currently known
about the roles of GnIH in stress-induced reproductive dysfunction.
PMID- 28424662
TI - Untangling Genomes of Novel Planctomycetal and Verrucomicrobial Species from
Monterey Bay Kelp Forest Metagenomes by Refined Binning.
AB - The kelp forest of the Pacific temperate rocky marine coastline of Monterey Bay
in California is a dominant habitat for large brown macro-algae in the order of
Laminariales. It is probably one of the most species-rich, structurally complex
and productive ecosystems in temperate waters and well-studied in terms of
trophic ecology. However, still little is known about the microorganisms thriving
in this habitat. A growing body of evidence suggests that bacteria associated
with macro-algae represent a huge and largely untapped resource of natural
products with chemical structures that have been optimized by evolution for
biological and ecological purposes. Those microorganisms are most likely
attracted by algae through secretion of specific carbohydrates and proteins that
trigger them to attach to the algal surface and to form biofilms. The algae might
then employ those bacteria as biofouling control, using their antimicrobial
secondary metabolites to defeat other bacteria or eukaryotes. We here analyzed
biofilm samples from the brown macro-algae Macrocystis pyrifera sampled in
November 2014 in the kelp forest of Monterey Bay by a metagenomic shotgun and
amplicon sequencing approach, focusing on Planctomycetes and Verrucomicrobia from
the PVC superphylum. Although not very abundant, we were able to find novel
Planctomycetal and Verrucomicrobial species by an innovative binning approach.
All identified species harbor secondary metabolite related gene clusters,
contributing to our hypothesis that through inter-species interaction,
microorganisms might have a substantial effect on kelp forest wellbeing and/or
disease-development.
PMID- 28424663
TI - Antimicrobial Photodynamic Therapy against Endodontic Enterococcus faecalis and
Candida albicans Mono and Mixed Biofilms in the Presence of Photosensitizers: A
Comparative Study with Classical Endodontic Irrigants.
AB - Endodontic biofilms eradication from the infected root canal system remains as
the primary focus in endodontic field. In this study, it was assessed the
efficacy of antimicrobial Photodynamic Therapy (aPDT) with the Zn(II)chlorin e6
methyl ester (Zn(II)e6Me) activated by red light against monospecies and mixed
biofilms of Enterococcus faecalis and Candida albicans. The results were compared
with the ones obtained with Rose Bengal (RB), Toluidine Blue-O (TBO), the
synthetic tetracationic porphyrin (TMPyP) as well as classical endodontic
irrigants (3% NaOCl, 17% EDTA and 2% CHX). The antimicrobial efficacy of aPDT
toward monospecies and mixed biofilms was quantified resorting to safranin red
method. The changes of biofilm organization and of cellular ultrastructure were
evaluated through several microscopy techniques (light, laser confocal and
transmission electron microscopy). Zn(II)e6Me once activated with light for 60 or
90 s was able to remove around 60% of the biofilm's biomass. It was more
efficient than TBO and RB and showed similar efficiency to TMPyP and classical
irrigants, CHX and EDTA. As desirable in a PS, Zn(II)e6Me in the dark showed
smaller activity than TMPyP. Only NaOCl revealed higher efficiency, with 70-90%
of the biofilm's biomass removal. The organization of biofilms and the normal
microbial cell ultrastructure were extensively damaged by the presence of
Zn(II)e6Me. aPDT with Zn(II)e6Me showed to be an efficient antimicrobial strategy
deserving further studies leading to a future clinical usage in endodontic
disinfection.
PMID- 28424664
TI - Spotted Fever: Epidemiology and Vector-Rickettsia-Host Relationship in Rio de
Janeiro State.
AB - The eco-epidemiological scenario of spotted fever (SF), a tick-borne disease that
affects humans and other animals in several countries around the world, was
analyzed in Rio de Janeiro (RJ) State, Brazil. During the last 34 years, 990 SF
cases were reported in RJ (the Brazilian state with the highest population
density), including 116 cases confirmed by serology (RIFI) or PCR, among 42.39%
of the municipalities with reported cases of SF. The epidemiologic dynamics of SF
in RJ State are very heterogeneous in time and space, with outbreaks, high
mortality rates and periods of epidemiological silence (no SF cases reported).
Furthermore, it exhibited a changing epidemiological profile from being rural to
becoming an urban disease. This study identified arthropods infected with
Rickettsia felis, R. bellii and R. rickettsii, and found that the abundance of
ectoparasites was associated with specific hosts. The R. rickettsii-vector-host
relationship was most evident in species-specific parasitism. This suggests that
the association between dogs, cattle, horses, capybaras and their main
ectoparasites, Rhipicephalus sanguineus and Ctenocephalides felis, Rhipicephalus
microplus, Dermacentor nitens, and Amblyomma dubitatum, respectively, has a key
role in the dynamics of R. rickettsii transmission in enzootic cycles and the
maintenance of carrier ectoparasites, thus facilitating the existence of endemic
areas with the ability to produce epidemic outbreaks of SF in RJ. This study
found confirmed human infections for only the R. rickettsii carrier Amblyomma
sculptum, which reinforces the importance of this species as a vector of the
pathogen in Brazil. This study can be adapted to different eco-epidemiological
scenarios of spotted fever throughout the Americas.
PMID- 28424665
TI - Ca. Similichlamydia in Epitheliocystis Co-infection of Gilthead Seabream Gills:
Unique Morphological Features of a Deep Branching Chlamydial Family.
AB - The Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum
constitutes a broad range of organisms with an intriguing array of
ultrastructural morphologies, including intracellular membranes and compartments
and their corresponding complex genomes encoding these forms. The phylum
Chlamydiae are all obligate intracellular bacteria and, although much is already
known of their genomes from various families and how these regulate the various
morphological forms, we know remarkably little about what is likely the deepest
rooting clade of this phylum, which has only been found to contain pathogens of
marine and fresh water vertebrates. The disease they are associated with is
called epitheliocystis; however, analyses of the causative agents is hindered by
an inability to cultivate them for refined in vitro experimentation. For this
reason, we have developed tools to analyse both the genomes and the
ultrastructures of bacteria causing this disease, directly from infected tissues.
Here we present structural data for a member of the family Ca.
Similichlamydiaceae from this deep-rooted clade, which we have identified using
molecular tools, in epitheliocystis lesions of gilthead seabream (Sparus aurata)
in Greece. We present evidence that the chlamydial inclusions appear to develop
in a perinuclear location, similar to other members of the phylum and that a
chlamydial developmental cycle is present, with chlamydial forms similar to
reticular bodies (RBs) and elementary bodies (EBs) detected. Division of the RBs
appeared to follow a budding process, and larger RBs with multiple condensed
nucleoids were detected using both transmission electron microscopy (TEM) and by
focused-ion beam, scanning electron microscopy (FIB-SEM). As model hosts, fish
offer many advantages for investigation, and we hope by these efforts to
encourage others to explore the biology of fish pathogens from the PVC.
PMID- 28424667
TI - Editorial: Plant Immunity against Viruses.
PMID- 28424666
TI - NapA Mediates a Redox Regulation of the Antioxidant Response, Carbon Utilization
and Development in Aspergillus nidulans.
AB - The redox-regulated transcription factors (TFs) of the bZIP AP1 family, such as
yeast Yap1 and fission yeast Pap1, are activated by peroxiredoxin proteins (Prxs)
to regulate the antioxidant response. Previously, Aspergillus nidulans mutants
lacking the Yap1 ortholog NapA have been characterized as sensitive to H2O2 and
menadione. Here we study NapA roles in relation to TFs SrrA and AtfA, also
involved in oxidant detoxification, showing that these TFs play different roles
in oxidative stress resistance, catalase gene regulation and development, during
A. nidulans life cycle. We also uncover novel NapA roles in repression of sexual
development, normal conidiation, conidial mRNA accumulation, and carbon
utilization. The phenotypic characterization of DeltagpxA, DeltatpxA, and
DeltatpxB single, double and triple peroxiredoxin mutants in wild type or
DeltanapA backgrounds shows that none of these Prxs is required for NapA function
in H2O2 and menadione resistance. However, these Prxs participate in a minor NapA
independent H2O2 resistance pathway and NapA and TpxA appear to regulate
conidiation along the same route. Using transcriptomic analysis we show that
during conidial development NapA-dependent gene expression pattern is different
from canonical oxidative stress patterns. In the course of conidiation, NapA is
required for regulation of at least 214 genes, including ethanol utilization
genes alcR, alcA and aldA, and large sets of genes encoding proteins involved in
transcriptional regulation, drug detoxification, carbohydrate utilization and
secondary metabolism, comprising multiple oxidoreductases, membrane transporters
and hydrolases. In agreement with this, DeltanapA mutants fail to grow or grow
very poorly in ethanol, arabinose or fructose as sole carbon sources. Moreover,
we show that NapA nuclear localization is induced not only by oxidative stress
but also by growth in ethanol and by carbon starvation. Together with our
previous work, these results show that SakA-AtfA, SrrA and NapA oxidative stress
sensing pathways regulate essential aspects of spore physiology (i.e., cell cycle
arrest, dormancy, drug production and detoxification, and carbohydrate
utilization).
PMID- 28424668
TI - Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its
Breakdown in Early Resuscitation Phase.
AB - Under gradual acidification of growth medium resulting in the formation of
dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in
dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64%
of total organic substances in the dormant cell extract was represented by
trehalose whilst the trehalose content in an extract of active cells taken from
early stationary phase was not more than 15%. Trehalose biosynthesis during
transition to the dormant state is provided by activation of genes involved in
the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the
concentration of free trehalose in dormant cells by expression of MSMEG_4535
coding for trehalase we found that cell viability depends on trehalose level:
cells with a high amount of trehalose survive much better than cells with a low
amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose
and an increase in glucose concentration occurred in the early period of
resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes
place at this time as a transient increase in trehalase activity was observed
between 1 and 3 h of resuscitation. Activation of trehalase was not due to de
novo biosynthesis but because of self-activation of the enzyme from the inactive
state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents
self-activation of trehalase in vitro and after activation the enzyme is still
sensitive to ATP we suggest that the transient character of trehalase activation
in cells is due to variation in intracellular ATP concentration found in the
early resuscitation period. The negative influence of the trehalase inhibitor
validamycin A on the resuscitation of dormant cells proves the importance of
trehalase for resuscitation. These experiments demonstrate the significance of
free trehalose accumulation for the maintenance of dormant mycobacterial
viability and the involvement of trehalose breakdown in early events leading to
cell reactivation similar to yeast and fungal spores.
PMID- 28424669
TI - Inferring Microbial Interactions in the Gut of the Hong Kong Whipping Frog
(Polypedates megacephalus) and a Validation Using Probiotics.
AB - The concerted activity of intestinal microbes is crucial to the health and
development of their host organisms. Investigation of microbial interactions in
the gut should deepen our understanding of how these micro-ecosystems function.
Due to advances in Next Generation Sequencing (NGS) technologies, various
bioinformatic strategies have been proposed to investigate these microbial
interactions. However, due to the complexity of the intestinal microbial
community and difficulties in monitoring their interactions, at present there is
a gap between the theory and biological application. In order to construct and
validate microbial relationships, we first induce a community shift from simple
to complex by manipulating artificial hibernation (AH) in the treefrog
Polypedates megacephalus. To monitor community growth and microbial interactions,
we further performed a time-course screen using a 16S rRNA amplicon approach and
a Lotka-Volterra model. Lotka-Volterra models, also known as predator-prey
equations, predict the dynamics of microbial communities and how communities are
structured and sustained. An interaction network of gut microbiota at the genus
level in the treefrog was constructed using Metagenomic Microbial Interaction
Simulator (MetaMIS) package. The interaction network obtained had 1,568
commensal, 1,737 amensal, 3,777 mutual, and 3,232 competitive relationships,
e.g., Lactococcus garvieae has a commensal relationship with Corynebacterium
variabile. To validate the interacting relationships, the gut microbe composition
was analyzed after probiotic trials using single strain (L. garvieae, C.
variabile, and Bacillus coagulans, respectively) and a combination of L.
garvieae, C. variabile, and B. coagulans, because of the cooperative relationship
among their respective genera identified in the interaction network. After a 2
week trial, we found via 16S rRNA amplicon analysis that the combination of
cooperative microbes yielded significantly higher probiotic concentrations than
single strains, and the immune response (interleukin-10 expression) also
significantly changed in a manner consistent with improved probiotic effects. By
taking advantage of microbial community shift from simple to complex, we thus
constructed a reliable microbial interaction network, and validated it using
probiotic strains as a test system.
PMID- 28424670
TI - Azathioprine, Mercaptopurine, and 5-Aminosalicylic Acid Affect the Growth of IBD
Associated Campylobacter Species and Other Enteric Microbes.
AB - Campylobacter concisus is a bacterium that is associated with inflammatory bowel
disease (IBD). Immunosuppressive drugs including azathioprine (AZA) and
mercaptopurine (MP), and anti-inflammatory drug such as 5-aminosalicylic acid (5
ASA) are commonly used to treat patients with IBD. This study aimed to examine
the effects of AZA, MP, and 5-ASA on the growth of IBD-associated bacterial
species and to identify bacterial enzymes involved in immunosuppressive drug
metabolism. A total of 15 bacterial strains of five species including 11 C.
concisus strains, Bacteroides fragilis, Bacteroides vulgatus, Enterococcus
faecalis, and Escherichia coli were examined. The impact of AZA, MP, and 5-ASA on
the growth of these bacterial species was examined quantitatively using a plate
counting method. The presence of enzymes involved in AZA and MP metabolism in
these bacterial species was identified using bioinformatics tools. AZA and MP
significantly inhibited the growth of all 11 C. concisus strains. C. concisus
strains were more sensitive to AZA than MP. 5-ASA showed inhibitory effects to
some C. concisus strains, while it promoted the growth of other C. concisus
strains. AZA and MP also significantly inhibited the growth of B. fragilis and B.
vulgatus. The growth of E. coli was significantly inhibited by 200 MUg/ml of AZA
as well as 100 and 200 MUg/ml of 5-ASA. Bacterial enzymes related to AZA and MP
metabolism were found, which varied in different bacterial species. In
conclusion, AZA and MP have inhibitory effects to IBD-associated C. concisus and
other enteric microbes, suggesting an additional therapeutic mechanism of these
drugs in the treatment of IBD. The strain dependent differential impact of 5-ASA
on the growth of C. concisus may also have clinical implication given that in
some cases 5-ASA medications were found to cause exacerbations of colitis.
PMID- 28424671
TI - Functional Characterization and Conditional Regulation of the Type VI Secretion
System in Vibrio fluvialis.
AB - Vibrio fluvialis is an emerging foodborne pathogen of increasing public health
concern. The mechanism(s) that contribute to the bacterial survival and disease
are still poorly understood. In other bacterial species, type VI secretion
systems (T6SSs) are known to contribute to bacterial pathogenicity by exerting
toxic effects on host cells or competing bacterial species. In this study, we
characterized the genetic organization and prevalence of two T6SS gene clusters
(VflT6SS1 and VflT6SS2) in V. fluvialis. VflT6SS2 harbors three "orphan" hcp-vgrG
modules and was more prevalent than VflT6SS1 in our isolates. We showed that
VflT6SS2 is functionally active under low (25 degrees C) and warm (30 degrees C)
temperatures by detecting the secretion of a T6SS substrate, Hcp. This finding
suggests that VflT6SS2 may play an important role in the survival of the
bacterium in the aquatic environment. The secretion of Hcp is growth phase
dependent and occurs in a narrow range of the growth phase (OD600 from 1.0 to
2.0). Osmolarity also regulates the function of VflT6SS2, as evidenced by our
finding that increasing salinity (from 170 to 855 mM of NaCl) and exposure to
high osmolarity KCl, sucrose, trehalose, or mannitol (equivalent to 340 mM of
NaCl) induced significant secretion of Hcp under growth at 30 degrees C.
Furthermore, we found that although VflT6SS2 was inactive at a higher temperature
(37 degrees C), it became activated at this temperature if higher salinity
conditions were present (from 513 to 855 mM of NaCl), indicating that it may be
able to function under certain conditions in the infected host. Finally, we
showed that the functional expression of VflT6SS2 is associated with anti
bacterial activity. This activity is Hcp-dependent and requires vasH, a
transcriptional regulator of T6SS. In sum, our study demonstrates that VflT6SS2
provides V. fluvialis with an enhanced competitive fitness in the marine
environment, and its activity is regulated by environmental signals, such as
temperature and osmolarity.
PMID- 28424672
TI - Isolation and Identification of the Indigenous Yeast Population during
Spontaneous Fermentation of Isabella (Vitis labrusca L.) Grape Must.
AB - Grape must harbors a complex community of yeast species responsible for
spontaneous alcoholic fermentation. Although there are detailed studies on the
microbiota of Vitis vinifera L. grapes, less is known about the diversity and
behavior of yeast communities present on fermenting grape must from other species
of Vitis. In this work, we used a culture-dependent method to study the identity
and dynamics of the indigenous yeast population present during the spontaneous
fermentation of Isabella (Vitis labrusca L.) grape must. Alcoholic fermentation
was conducted using standard enological practices, and the associated non
Saccharomyces and S. cerevisiae yeast community was analyzed using selective
growth media and 5.8-ITS DNA sequencing. Candida californica, Candida hellenica,
Starmerella bacillaris (synonym Candida zemplinina), Hanseniaspora uvarum, and
Hanseniaspora vineae were the main non-Saccharomyces species identified on
Isabella fermenting must. Issatchenkia hanoiensis, a yeast species rarely found
on Vitis vinifera L. grapes, was also recognized on Isabella grape must. Candida
azymoides, Candida californica and Pichia cecembensis, identified in this work on
Isabella fermenting must, have not previously been found on Vitis vinifera L.
grape must. Interestingly, C. azymoides, I. hanoiensis and P. cecembensis have
recently been isolated from the surface of Vitis labrusca L. grapes from
vineyards in the Azores archipelago, suggesting that specific Vitis-yeast species
associations are formed independently of geographic origin. We suggest that C.
azymoides, C. californica, and P. cecembensis are yeast species preferentially
associated with Vitis labrusca L. grapes. Specific biological interactions
between grapevines and yeast species may underlie the assembly of differential
Vitis-microbial communities.
PMID- 28424673
TI - Genome-Scale Reconstruction of the Metabolic Network in Oenococcus oeni to Assess
Wine Malolactic Fermentation.
AB - Oenococcus oeni is the main responsible agent for malolactic fermentation in
wine, an unpredictable and erratic process in winemaking. To address this, we
have constructed and exhaustively curated the first genome-scale metabolic model
of Oenococcus oeni, comprising 660 reactions, 536 metabolites and 454 genes. In
silico experiments revealed that nutritional requirements are predicted with an
accuracy of 93%, while 14 amino acids were found to be essential for the growth
of this bacterial species. When the model was applied to determine the non-growth
associated maintenance, results showed that O. oeni grown at 12% ethanol
concentration spent 30 times more ATP to stay alive than in the absence of
ethanol. Most of this ATP is employed for extruding protons outside of the cell.
A positive relationship was also found between specific consumption rates of
fructose, amino acids, oxygen, and malic acid and the specific production rates
of erythritol, lactate, and acetate, according to the ethanol content of the
medium. The metabolic model reconstructed here represents a unique tool to
predict the successful completion of wine malolactic fermentation carried out
either by different strains of Oenococcus oeni, as well as at any particular
physico-chemical composition of wine. It will also allow the development of
consortium metabolic models that could be applied to winemaking to simulate and
understand the interactions between O. oeni and other microorganisms that share
this ecological niche.
PMID- 28424675
TI - Safety, Protective Immunity, and DIVA Capability of a Rough Mutant Salmonella
Pullorum Vaccine Candidate in Broilers.
AB - Salmonella enterica subsp. enterica serovar Gallinarum biovar Pullorum
(Salmonella Pullorum) is highly adapted to chickens causing an acute systemic
disease that results in high mortality. Vaccination represents one approach for
promoting animal health, food safety and reducing environmental persistence in
Salmonella control. An important consideration is that Salmonella vaccination in
poultry should not interfere with the salmonellosis monitoring program. This is
the basis of the DIVA (Differentiation of Infected and Vaccinated Animals)
program. In order to achieve this goal, waaL mutant was developed on a spiC
mutant that was developed previously. The safety, efficacy, and DIVA features of
this vaccine candidate (Salmonella Pullorum DeltaspiCDeltawaaL) were evaluated in
broilers. Our results show that the truncated LPS in the vaccine strain has a
differentiating use as both a bacteriological marker (rough phenotype) and also
as a serological marker facilitating the differentiation between infected and
vaccinated chickens. The rough mutant showed adequate safety being avirulent in
the host chicks and showed increased sensitivity to environmental stresses.
Single intramuscular immunization of day-old broiler chicks with the mutant
confers ideal protection against lethal wild type challenge by significantly
stimulating both humoral and cellular immune responses as well as reducing the
colonization of the challenge strain. Significantly lower mean pathology scores
were observed in the vaccination group compared to the control group.
Additionally, the mutant strain generated cross-protection against challenge with
the wild type Salmonella Gallinarum thereby improving survival and with the wild
type Salmonella Enteritidis thereby reducing colonization. These results suggest
that the double-mutant strain may be a safe, effective, and cross-protective
vaccine against Salmonella infection in chicks while conforming to the
requirements of the DIVA program.
PMID- 28424674
TI - Global Fecal and Plasma Metabolic Dynamics Related to Helicobacter pylori
Eradication.
AB - Background:Helicobacter pylori colonizes the gastric mucosa of more than half of
the world's population. There is increasing evidence H. pylori protects against
the development of obesity and childhood asthma/allergies in which the
development of these diseases coincide with transient dysbiosis. However, the
mechanism underlying the association of H. pylori eradication with human
metabolic and immunological disorders is not well-established. In this study, we
aimed to investigate the local and systemic effects of H. pylori eradication
through untargeted fecal lipidomics and plasma metabolomics approaches by liquid
chromatography mass spectrometry (LC-MS). Results: Our study revealed that
eradication of H. pylori eradication (i.e., loss of H. pylori and/or H. pylori
eradication therapy) changed many global metabolite/lipid features, with the
majority being down-regulated. Our findings primarily show that H. pylori
eradication affects the host energy and lipid metabolism which may eventually
lead to the development of metabolic disorders. Conclusion: These predictive
metabolic signatures of metabolic and immunological disorders following H. pylori
eradication can provide insights into dynamic local and systemic metabolism
related to H. pylori eradication in modulating human health.
PMID- 28424676
TI - Seasonal Fluctuations of Microbial Aerosol in Live Poultry Markets and the
Detection of Endotoxin.
AB - Microbial aerosol whose species and concentrations are closely related to human
health is ubiquitous. The effect of microbes on human and animal health and
production performance is, in many cases, caused by the spreading of air. Samples
in this experiment were from a live poultry market (LPM) in Tai'an, China,
collected three times a day (8 am, 14 pm, and 20 pm) over three consecutive days
each month for 11 months (Original sampling plan was a year, the government due
to the environmental protection, the was LPM closed). The main indicators of the
test were concentrations of cultural airborne bacteria, airborne fungi, and Gram
negative bacteria. At the same time the species of Gram-negative bacteria and the
concentration of endotoxin were tested. Temperature and humidity were recorded in
the process of each sampling. The results showed that the diurnal variation of
the concentration of bacteria, fungi, and Gram-negative bacteria is higher in the
morning and evening, but lower at noon. The concentrations of airborne bacteria
and Gram-negative bacteria increased in earlier months and decreased in later
months, with the peak appearing in the autumn. The concentration of fungi showed
a decrease first and then tended to stabilize, with the peak occurring in the
spring. The concentration peak of endotoxin occurred in the summer. Endotoxin
levels were significantly correlated with humidity (r = 0.90, p < 0.01). Most
bacteria were distributed at the third and fourth stages (2.1-4.7 MUm) in the
ANDERSEN-6 sampler. The dominant species of Gram-negative bacteria during the
four seasons were Pseudomonas aeruginosa, Acinetobacter, Klebsiella pneumoniae,
and Salmonella. In China, people have a habit of eating fresh poultry, LPM
distribution is widespread, stream of people and traffic flow are large, easily
caused the spread of bacteria and viruses, so the LPM microbial aerosol research
have significant public health implications.
PMID- 28424677
TI - Responses of the Housefly, Musca domestica, to the Hytrosavirus Replication:
Impacts on Host's Vitellogenesis and Immunity.
AB - Hytrosaviridae family members replicate in the salivary glands (SGs) of their
adult dipteran hosts and are transmitted to uninfected hosts via saliva during
feeding. Despite inducing similar gross symptoms (SG hypertrophy; SGH),
hytrosaviruses (SGHVs) have distinct pathobiologies, including sex-ratio
distortions in tsetse flies and refusal of infected housefly females to copulate.
Via unknown mechanism(s), SGHV replication in other tissues results in reduced
fecundity in tsetse flies and total shutdown of vitellogenesis and sterility in
housefly females. We hypothesized that vitellogenesis shutdown was caused by
virus-induced modulation of hormonal titers. Here, we used RNA-Seq to investigate
virus-induced modulation of host genes/pathways in healthy and virus-infected
houseflies, and we validated expression of modulated genes (n = 23) by RT-qPCR.
We also evaluated the levels and activities of hemolymph AMPs, levels of
endogenous sesquiterpenoids, and impacts of exogenous hormones on ovarian
development in viremic females. Of the 973 housefly unigenes that were
significantly modulated (padj <= 0.01, log2FC <= -2.0 or >= 2.0), 446 and 527
genes were downregulated and upregulated, respectively. While the most
downregulated genes were related to reproduction (embryogenesis/oogenesis), the
repertoire of upregulated genes was overrepresented by genes related to non-self
recognition, ubiquitin-protease system, cytoskeletal traffic, cellular
proliferation, development and movement, and snRNA processing. Overall, the
virus, Musca domestica salivary gland hytrosavirus (MdSGHV), induced the
upregulation of various components of the siRNA, innate antimicrobial immune, and
autophagy pathways. We show that MdSGHV undergo limited morphogenesis in the
corpora allata/corpora cardiaca (CA/CC) complex of M. domestica. MdSGHV
replication in CA/CC potentially explains the significant reduction of hemolymph
sesquiterpenoids levels, the refusal to mate, and the complete shutdown of egg
development in viremic females. Notably, hormonal rescue of vitellogenesis did
not result in egg production. The mechanism underlying MdSGHV-induced sterility
has yet to be resolved.
PMID- 28424678
TI - Microbial and Isotopic Evidence for Methane Cycling in Hydrocarbon-Containing
Groundwater from the Pennsylvania Region.
AB - The Pennsylvania region hosts numerous oil and gas reservoirs and the presence of
hydrocarbons in groundwater has been locally observed. However, these methane
containing freshwater ecosystems remain poorly explored despite their potential
importance in the carbon cycle. Methane isotope analysis and analysis of low
molecular weight hydrocarbon gases from 18 water wells indicated that active
methane cycling may be occurring in methane-containing groundwater from the
Pennsylvania region. Consistent with this observation, multigenic qPCR and gene
sequencing (16S rRNA genes, mcrA, and pmoA genes) indicated abundant populations
of methanogens, ANME-2d (average of 1.54 * 104mcrA gene per milliliter of water)
and bacteria associated with methane oxidation (NC10, aerobic methanotrophs,
methylotrophs; average of 2.52 * 103pmoA gene per milliliter of water). Methane
cycling therefore likely represents an important process in these hydrocarbon
containing aquifers. The microbial taxa and functional genes identified and
geochemical data suggested that (i) methane present is at least in part due to
methanogens identified in situ; (ii) Potential for aerobic and anaerobic methane
oxidation is important in groundwater with the presence of lineages associated
with both anaerobic an aerobic methanotrophy; (iii) the dominant methane
oxidation process (aerobic or anaerobic) can vary according to prevailing
conditions (oxic or anoxic) in the aquifers; (iv) the methane cycle is closely
associated with the nitrogen cycle in groundwater methane seeps with methane
and/or methanol oxidation coupled to denitrification or nitrate and nitrite
reduction.
PMID- 28424679
TI - Linking Diet to Colorectal Cancer: The Emerging Role of MicroRNA in the
Communication between Plant and Animal Kingdoms.
AB - Environmental and lifestyle factors, including diet and nutritional habits have
been strongly linked to colorectal cancer (CRC). Of note, unhealthy dietary
habits leading to adiposity represent a main risk factor for CRC and are
associated with a chronic low-grade inflammatory status. Inflammation is a
hallmark of almost every type of cancer and can be modulated by several food
compounds exhibiting either protective or promoting effects. However, in spite of
an extensive research, the underlying mechanisms by which dietary patterns or
bioactive food components may influence tumor onset and outcome have not been
fully clarified yet. Growing evidence indicates that diet, combining beneficial
substances and potentially harmful ingredients, has an impact on the expression
of key regulators of gene expression such as the non-coding RNA (ncRNA). Since
the expression of these molecules is deranged in chronic inflammation and cancer,
modulating their expression may strongly influence the cancer phenotype and
outcomes. In addition, the recently acquired knowledge on the existence of
intricate inter-kingdom communication networks, is opening new avenues for a
deeper understanding of the intimate relationships linking diet to CRC. In this
novel scenario, diet-modulated ncRNA may represent key actors in the interaction
between plant and animal kingdoms, capable of influencing disease onset and
outcome. In this review, we will summarize the studies demonstrating a link
between bioactive food components, including food-derived, microbiota-processed,
secondary metabolites, and host ncRNA. We will focus on microRNA, highlighting
how this plant/animal inter-kingdom cross-talk may have an impact on CRC
establishment and progression.
PMID- 28424680
TI - Induction of Protective Immunity against Toxoplasma gondii in Mice by Nucleoside
Triphosphate Hydrolase-II (NTPase-II) Self-amplifying RNA Vaccine Encapsulated in
Lipid Nanoparticle (LNP).
AB - RNA-based vaccine represents an irresistible and safe immunization strategy with
decreasing theoretical risks of genomic integration and malignant cell
transformation. To our knowledge, however, there is no report about development
of RNA vaccine against Toxoplasma gondii infection. We have previously
demonstrated that the recombinant T. gondii nucleoside triphosphate hydrolase-II
(NTPase-II) protein is able to provide protective Th1 cell-mediated immunity
against T. gondii. Herein, we evaluated the immunogenic potential of a self
amplifying RNA vaccine-encoding T. gondii NTPase-II gene, RREP-NTPase-II,
delivered by a synthetic lipid nanoparticle (LNP). Immunization of mice with
naked RREP-NTPase-II induced a strong cellular and humoral immune response with
high-IgG antibody titers and IFN-gamma production. The immunized mice displayed
significantly prolonged survival time and reduction in brain parasite load
(46.4%) compared with control group. Furthermore, mice vaccinated with RREP
NTPase-II-encapsulated LNP displayed significantly enhanced protection against
acute infection as well as chronic infection with PRU cyst, which shows 62.1%
reduction in brain cyst burden in comparison to control group. These results
suggest that the combination of self-amplifying RNA and LNP ion would be
beneficial to the development of a safe and long-acting vaccine against
toxoplasmosis.
PMID- 28424681
TI - The Spontaneous Autoimmune Neuromyopathy in ICOSL-/- NOD Mice Is CD4+ T-Cell and
Interferon-gamma Dependent.
AB - Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of
diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the
development of a spontaneous autoimmune neuromyopathy. At the pathological level,
ICOSL-/- NOD mice show stronger protection from insulitis than their ICOS-/-
counterparts. Also, the ICOSL-/- NOD model carries a limited C57BL/6 region
containing the Icosl nul mutation, but, in contrast to ICOS-/- NOD mice, no gene
variant previously reported as associated to NOD diabetes. Therefore, we aimed at
providing a detailed characterization of the ICOSL-/- NOD model. The phenotype
observed in ICOSL-/- NOD mice is globally similar to that observed in ICOS-/- and
ICOS-/-ICOSL-/- double-knockout NOD mice, manifested by a progressive locomotor
disability first affecting the front paws as observed by catwalk analysis and a
decrease in grip test performance. The pathology remains limited to peripheral
nerve and striated muscle. The muscle disease is characterized by myofiber
necrosis/regeneration and an inflammatory infiltrate composed of CD4+ T-cells,
CD8+ T-cells, and myeloid cells, resembling human myositis. Autoimmune
neuromyopathy can be transferred to NOD.scid recipients by CD4+ but not by CD8+ T
cells isolated from 40-week-old female ICOSL-/- NOD mice. The predominant role of
CD4+ T-cells is further demonstrated by the observation that neuromyopathy does
not develop in CIITA-/-ICOSL-/- NOD in contrast to beta2microglobulin-/-ICOSL-/-
NOD mice. Also, the cytokine profile of CD4+ T-cells infiltrating muscle and
nerve of ICOSL-/- NOD mice is biased toward a Th1 pattern. Finally, adoptive
transfer experiments show that diabetes development requires expression of ICOSL,
in contrast to neuromyopathy. Altogether, the deviation of autoimmunity from the
pancreas to skeletal muscles in the absence of ICOS/ICOSL signaling in NOD mice
is strictly dependent on CD4+ T-cells, leads to myofiber necrosis and
regeneration. It provides the first mouse model of spontaneous autoimmune
myopathy akin to human myositis.
PMID- 28424683
TI - Novel Strategy to Expand Super-Charged NK Cells with Significant Potential to
Lyse and Differentiate Cancer Stem Cells: Differences in NK Expansion and
Function between Healthy and Cancer Patients.
AB - Natural killer (NK) cells are known to target cancer stem cells and
undifferentiated tumors. In this paper, we provide a novel strategy for expanding
large numbers of super-charged NK cells with significant potential to lyse and
differentiate cancer stem cells and demonstrate the differences in the dynamics
of NK cell expansion between healthy donors and cancer patients. Decline in
cytotoxicity and lower interferon (IFN)-gamma secretion by osteoclast (OC)
expanded NK cells from cancer patients correlates with faster expansion of
residual contaminating T cells within purified NK cells, whereas healthy donors'
OCs continue expanding super-charged NK cells while limiting T cell expansion for
up to 60 days. Similar to patient NK cells, NK cells from tumor-bearing BLT
humanized mice promote faster expansion of residual T cells resulting in
decreased numbers and function of NK cells, whereas NK cells from mice with no
tumor continue expanding NK cells and retain their cytotoxicity. In addition,
dendritic cells (DCs) in contrast to OCs are found to promote faster expansion of
residual T cells within purified NK cells resulting in the decline in NK cell
numbers from healthy individuals. Addition of anti-CD3 mAb inhibits T cell
proliferation while enhancing NK cell expansion; however, expanding NK cells have
lower cytotoxicity but higher secretion of IFN-gamma. Expansion and functional
activation of super-charged NK cells by OCs is dependent on interleukin (IL)-12
and IL-15. Thus, in this report, we not only provide a novel strategy to expand
super-charged NK cells, but also demonstrate that rapid and sustained expansion
of residual T cells within the purified NK cells during expansion with DCs or OCs
could be a potential mechanism by which the numbers and function of NK cells
decline in cancer patients and in BLT-humanized mice.
PMID- 28424684
TI - Modulation of Human Leukocyte Antigen-C by Human Cytomegalovirus Stimulates
KIR2DS1 Recognition by Natural Killer Cells.
AB - The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human
leukocyte antigen (HLA) class I molecules has been characterized in detail. By
contrast, activating members of the KIR family, although closely related to
inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1
is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA
C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell
reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a
modified DAP12 adaptor protein. KIR2DS1 reporter cells were not activated upon
coculture with 721.221 cells transfected with different HLA-C molecules, or with
interferon-gamma stimulated primary dermal fibroblasts. However, KIR2DS1 reporter
cells and KIR2DS1+ primary natural killer (NK) cells were activated by C2-HLA-C
homozygous human fetal foreskin fibroblasts (HFFFs) but only after infection with
specific clones of a clinical strain of human cytomegalovirus (HCMV). Active
viral gene expression was required for activation of both cell types. Primary
NKG2A-KIR2DS1+ NK cell subsets degranulated after coculture with HCMV-infected
HFFFs. The W6/32 antibody to HLA class I blocked the KIR2DS1 reporter cell
interaction with its ligand on HCMV-infected HFFFs but did not block interaction
with KIR2DL1. This implies a differential recognition of HLA-C by KIR2DL1 and
KIR2DS1. The data suggest that modulation of HLA-C by HCMV is required for a
potent KIR2DS1-mediated NK cell activation.
PMID- 28424685
TI - Analysis of Linear Antibody Epitopes on Factor H and CFHR1 Using Sera of Patients
with Autoimmune Atypical Hemolytic Uremic Syndrome.
AB - INTRODUCTION: In autoimmune atypical hemolytic uremic syndrome (aHUS), the
complement regulator factor H (FH) is blocked by FH autoantibodies, while 90% of
the patients carry a homozygous deletion of its homolog complement FH-related
protein 1 (CFHR1). The functional consequence of FH-blockade is widely
established; however, the molecular basis of autoantibody binding and the role of
CFHR1 deficiency in disease pathogenesis are still unknown. We performed epitope
mapping of FH to provide structural insight in the autoantibody recruitment on FH
and potentially CFHR1. METHODS: Eight anti-FH positive aHUS patients were
enrolled in this study. With overlapping synthetic FH and CFHR1 peptides, we
located the amino acids (aa) involved in binding of acute and convalescence stage
autoantibodies. We confirmed the location of the mapped epitopes using
recombinant FH domains 19-20 that carried single-aa substitutions at the
suspected antibody binding sites in three of our patients. Location of the linear
epitopes and the introduced point mutations was visualized using crystal
structures of the corresponding domains of FH and CFHR1. RESULTS: We identified
three linear epitopes on FH (aa1157-1171; aa1177-1191; and aa1207-1226) and one
on CFHR1 (aa276-290) that are recognized both in the acute and convalescence
stages of aHUS. We observed a similar extent of autoantibody binding to the aHUS
specific epitope aa1177-1191 on FH and aa276-290 on CFHR1, despite seven of our
patients being deficient for CFHR1. Epitope mapping with the domain constructs
validated the location of the linear epitopes on FH with a distinct autoantibody
binding motif within aa1183-1198 in line with published observations. SUMMARY:
According to the results, the linear epitopes we identified are located close to
each other on the crystal structure of FH domains 19-20. This tertiary
configuration contains the amino acids reported to be involved in C3b and sialic
acid binding on the regulator, which may explain the functional deficiency of FH
in the presence of autoantibodies. The data we provide identify the exact
structures involved in autoantibody recruitment on FH and confirm the presence of
an autoantibody binding epitope on CFHR1.
PMID- 28424682
TI - Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis:
Lessons Learned from Autoimmune Diseases.
AB - The classical paradigm of tuberculosis (TB) immunity, with a central protective
role for Th1 responses and IFN-gamma-stimulated cellular responses, has been
challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1
immunity. Moreover, preclinical TB models have shown that increasing IFN-gamma
responses in the lungs is more damaging to the host than to the pathogen. Type 1
interferon signaling and altered Th17 responses have also been associated with
active TB, but their functional roles in TB pathogenesis remain to be
established. These two host responses have been studied in more detail in
autoimmune diseases (AID) and show functional interactions that are of potential
interest in TB immunity. In this review, we first identify the role of type 1
interferons and Th17 immunity in TB, followed by an overview of interactions
between these responses observed in systemic AID. We discuss (i) the effects of
GM-CSF-secreting Th17.1 cells and type 1 interferons on CCR2+ monocytes; (ii)
convergence of IL-17 and type 1 interferon signaling on stimulating B-cell
activating factor production and the central role of neutrophils in this process;
and (iii) synergy between IL-17 and type 1 interferons in the generation and
function of tertiary lymphoid structures and the associated follicular helper T
cell responses. Evaluation of these autoimmune-related pathways in TB
pathogenesis provides a new perspective on recent developments in TB research.
PMID- 28424686
TI - Mucosal and Systemic Immune Responses to Influenza H7N9 Antigen HA1-2 Co
Delivered Intranasally with Flagellin or Polyethyleneimine in Mice and Chickens.
AB - Consecutive cases of human infection with H7N9 influenza viruses since 2013 in
China have prompted efforts to develop an effective treatment. Subunit vaccines
introduced by intranasal administration can block an infection at its primary
site; flagellin (fliC) and polyethyleneimine (PEI) have been shown to be potent
adjuvants. We previously generated the hemagglutinin (HA)1-2-fliC fusion protein
consisting of the globular head domain (HA1-2; amino acids 62-284) of HA fused
with Salmonella typhimurium fliC. In the present study, we investigated its
effectiveness of both flagellin and PEI as mucosal adjuvants for the H7N9
influenza subunit vaccine. Mice immunized intranasally with HA1-2-fliC and HA1-2
PEI showed higher HA1-2-specific immunoglobulin (Ig)G and IgA titers in serum,
nasal wash, and bronchial alveolar lavage fluid. Moreover, splenocyte activation
and proliferation and the number of HA1-2-specific interferon (IFN)-gamma- and
interleukin (IL)-4-producing splenocytes were markedly increased in the fliC and
PEI groups; in the latter, there were more cells secreting IL-4 than IFN-gamma,
suggesting that fliC induced T helper type (Th)1 and Th2 immune responses, and
PEI induced Th2-biased responses, consistent with the serum antibody isotype
pattern (IgG1/IgG2a ratio). Furthermore, virus challenge was performed in a
chicken model. The results showed that chickens receiving fliC and PEI adjuvant
vaccine exhibited robust immune responses leading to a significant reduction in
viral loads of throat and cloaca compared to chickens receiving only HA1-2. These
findings provide a basis for the development of H7N9 influenza HA1-2 mucosal
subunit vaccines.
PMID- 28424687
TI - CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident
Memory Transcriptional Profile.
AB - During chronic infection, memory T cells acquire a unique phenotype and become
dependent on different survival signals than those needed for memory T cells
generated during an acute infection. The distinction between the role of effector
and memory T cells in an environment of persistent antigen remains unclear. Here,
in the context of chronic Toxoplasma gondii infection, we demonstrate that a
population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype
accumulates within the brain. We show that this population is distributed
throughout the brain in both parenchymal and extraparenchymal spaces.
Furthermore, this population is transcriptionally distinct and exhibits a
transcriptional signature consistent with the TRM observed in acute viral
infections. Finally, we establish that the CD103+ TRM population has an intrinsic
capacity to produce both IFN-gamma and TNF-alpha, cytokines critical for parasite
control within the central nervous system (CNS). The contribution of this
population to pro-inflammatory cytokine production suggests an important role for
TRM in protective and ongoing immune responses in the infected CNS. Accession
number: GSE95105.
PMID- 28424689
TI - Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during
Inflammatory Gum Disease.
AB - Periodontal inflammation is one of the most common chronic inflammatory
conditions in humans. Despite recent advances in identifying and characterizing
oral microbiota dysbiosis in the pathogenesis of gum disease, just how host
factors maintain a healthy homeostatic oral microbial community or prevent the
development of a pathogenic oral microbiota remains poorly understood. An
important determinant of microbiota fate is local antimicrobial proteins. Here,
we report that chemoattractant protein chemerin, which we recently identified as
a potent endogenous antimicrobial agent in body barriers such as the skin, is
present in the oral cavity under homeostatic and inflammatory conditions.
Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against
select bacteria strategically positioned in dental biofilm. Gingival crevicular
samples from patients with gingivitis but not periodontitis contain abundant
bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration.
Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin.
Together, these data suggest that as an antimicrobial agent and leukocyte
chemoattractant, chemerin likely contributes to antimicrobial immune defense in
the oral cavity.
PMID- 28424688
TI - Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New
Perspectives of Antimicrobial Peptide-Based Therapies.
AB - While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there
are concerns regarding possible side effects related to the unwanted suppression
of antimicrobial immunity leading to an increased risk of infection. Conversely,
recent data show that MSCs exert strong antimicrobial effects through indirect
and direct mechanisms, partially mediated by the secretion of antimicrobial
peptides and proteins (AMPs). In fact, MSCs have been reported to increase
bacterial clearance in preclinical models of sepsis, acute respiratory distress
syndrome, and cystic fibrosis-related infections. This article reviews the
current evidence regarding the direct antimicrobial effector function of MSCs,
focusing mainly on the role of MSCs-derived AMPs. The strategies that might
modulate the expression and secretion of these AMPs, leading to enhanced
antimicrobial effect, are highlighted. Furthermore, studies evaluating the
presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as
perspective opportunities to develop new drug delivery tools. The antimicrobial
potential of MSCs-derived EVs can also be heightened through cell conditioning
and/or drug loading. Finally, improving the pharmacokinetics and delivery, in
addition to deciphering the multi-target drug status of AMPs, should
synergistically lead to key advances against infections caused by drug-resistant
strains.
PMID- 28424690
TI - Bacillus subtilis Improves Immunity and Disease Resistance in Rabbits.
AB - Probiotics such as Lactobacillus and Bifidobacterium have been successfully used
to promote growth and prevent diseases. Previous reports have demonstrated that
Bacillus subtilis (B. subtilis) was a potential probiotic for animals. In this
research, 180 B. subtilis were isolated from the soil, identified, and
investigated in vitro. Furthermore, five B. subtilis were selected and mixed to
investigate their effect on growth performance, immune response, intestine
microbiota, and disease resistance in rabbits. Rabbits with a diet of 106 CFU g-1
mixed B. subtilis exhibited the best growth performance and higher serum IgG and
IgA than controls (P < 0.05). Moreover, dairy with B. subtilis can promote the
balance of intestinal flora. The major proinflammatory factor and beta-defensin
were upregulated compared with the controls. After 7 weeks of feeding, the
survival rate of the rabbits fed with B. subtilis was significantly higher than
those in the control groups postinfected with Escherichia coli. At the same time,
this study detected higher expression of beta-defensin and reduced bacteria
contents of the heart and cecal contents from the diet mixed with B. subtilis
compared with the control groups. In conclusion, dietary supplementation with B.
subtilis for rabbits could improve growth performance, intestinal homeostasis,
and immune organ index and enhance innate immune response as well as disease
resistance. These findings showed that the induction of beta-defensin by B.
subtilis might be an interesting new therapeutic strategy to strengthen innate
defense mechanisms.
PMID- 28424691
TI - Increased Autophagy-Related 5 Gene Expression Is Associated with Collagen
Expression in the Airways of Refractory Asthmatics.
AB - BACKGROUND: Fibrosis, particularly excessive collagen deposition, presents a
challenge for treating asthmatic individuals. At present, no drugs can remove or
reduce excessive collagen in asthmatic airways. Hence, the identification of
pathways involved in collagen deposition would help to generate therapeutic
targets to interfere with the airway remodeling process. Autophagy, a cellular
degradation process, has been shown to be dysregulated in various fibrotic
diseases, and genetic association studies in independent human populations have
identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis.
Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic
airways. OBJECTIVE: This study aimed to determine if (1) collagen deposition in
asthmatic airways is associated with ATG5 expression and (2) ATG5 protein
expression is associated with asthma per se and severity. METHODS: Gene
expression of transforming growth factor beta 1, various asthma-related collagen
types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III,
alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and
ATG5 were measured using mRNA isolated from bronchial biopsies of refractory
asthmatic subjects and assessed for pairwise associations. Protein expression of
ATG5 in the airways was measured and associations were assessed for asthma per
se, severity, and lung function. MAIN RESULTS: In refractory asthmatic
individuals, gene expression of ATG5 was positively associated with COL5A1 in the
airways. No association was detected between ATG5 protein expression and asthma
per se, severity, and lung function. CONCLUSION AND CLINICAL RELEVANCE: Positive
correlation between the gene expression patterns of ATG5 and COL5A1 suggests that
dysregulated autophagy may contribute to subepithelial fibrosis in the airways of
refractory asthmatic individuals. This finding highlights the therapeutic
potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat
refractory asthmatic individuals.
PMID- 28424693
TI - Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation.
AB - Evolution of melanoma from a primary tumor to widespread metastasis is crucially
dependent on lymphatic spread. The mechanisms regulating the initial step in
metastatic dissemination via regional lymph nodes remain largely unknown;
however, evidence supporting the establishment of a pre-metastatic niche is
evolving. We have previously described a dysfunctional immune profile including
reduced expression of dendritic cell (DC) maturation markers in the first node
draining from the primary tumor, the sentinel lymph node (SLN). Importantly, this
phenotype is present prior to evidence of nodal metastasis. Herein, we evaluate
melanoma-derived extracellular vesicles (EVs) as potential mediators of the
premetastatic niche through cargo-specific polarization of DCs. DCs matured in
vitro in the presence of melanoma EVs demonstrated significantly impaired
expression of CD83 and CD86 as well as decreased expression of Th1 polarizing
chemokines Flt3L and IL15 and migration chemokines MIP-1alpha and MIP-1beta
compared to liposome-treated DCs. Profiling of melanoma EV cargo identified
shared proteomic and RNA signatures including S100A8 and S100A9 protein cargo,
which in vitro compromised DC maturation similar to melanoma EVs. Early evidence
demonstrates that similar EVs can be isolated from human afferent lymphatic fluid
ex vivo. Taken together, here, we propose melanoma EV cargo as a mechanism by
which DC maturation is compromised warranting further study to consider this as a
potential mechanism enabled by the primary tumor to establish the premetastatic
niche in tumor-draining SLNs of patients.
PMID- 28424692
TI - T Cells in Osteoarthritis: Alterations and Beyond.
AB - Although osteoarthritis (OA) has been traditionally regarded as a non
inflammatory disease, reports increasingly suggest that it is inflammatory, at
least in certain patients. OA patients often exhibit inflammatory infiltration of
synovial membranes by macrophages, T cells, mast cells, B cells, plasma cells,
natural killer cells, dendritic cells, granulocytes, etc. Although previous
reviews have summarized the knowledge of inflammation in the pathogenesis of OA,
as far as we know, no report review our current understanding about T cells,
especially, each T cell subtype, in the biology of OA. This review highlights the
current understanding of the role of T cells in the pathogenesis of OA, with
attention to Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, regulatory
T cells, follicular helper T cells, cytotoxic T cells, T memory cells, and even
unconventional T cells (e.g., gammadelta T cells and cluster of differentiation 1
restricted T cells). The findings highlight the importance of T cells to the
development and progression of OA and suggest new therapeutic approaches for OA
patients based on the manipulation of T-cell responses.
PMID- 28424694
TI - Immune Responses in the Central Nervous System Are Anatomically Segregated in a
Non-Human Primate Model of Human Immunodeficiency Virus Infection.
AB - The human immunodeficiency virus (HIV) accesses the central nervous system (CNS)
early during infection, leading to HIV-associated cognitive impairment and
establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory
responses in different CNS regions in simian immunodeficiency virus (SIV)
infected macaques, a model for HIV infection. We found increased expression of
inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV
infected macaques. Conversely, the frontal lobe showed downregulation of
inflammatory genes associated with interferon-gamma and interleukin-6 pathways,
and absence of perivascular cuffing. These immunologic alterations were not
accompanied by differences in SIV transcriptional activity within the tissue.
Altered expression of genes associated with neurotoxicity was observed in both
midbrain and frontal lobe. The segregation of inflammatory responses to specific
regions of the CNS may both account for HIV-associated neurological symptoms and
constitute a critical hurdle for HIV eradication by shielding the CNS viral
reservoir from antiviral immunity.
PMID- 28424695
TI - B Cell Tolerance to Deiminated Histones in BALB/c, C57BL/6, and Autoimmune-Prone
Mouse Strains.
AB - Deimination, a posttranslational modification of arginine to citrulline carried
out by peptidylarginine deiminases, may compromise tolerance of self-antigens.
Patients with connective tissue autoimmunity, particularly rheumatoid arthritis
(RA), systemic lupus erythematosus (SLE), or Felty's syndrome, present with
autoantibodies to deiminated histones (dH), which thus form a category of
antibodies to citrullinated protein antigens (ACPA). In general, ACPA are a
sensitive diagnostic for RA and may form in response to the release of nuclear
chromatin (DNA plus dH) from granulocytes, usually referred to as neutrophil
extracellular traps. The aim of this study was to examine spontaneously
autoimmune mice for autoantibodies and T cell responses to dH. We compared IgG
binding to deiminated and non-deiminated histones (nH) by ELISA and Western
blotting in spontaneously autoimmune strains of (NZB * NZW) F1 and NZM2410
together with their derivative congenic strains, C57BL/6.Sle1 and
C57BL/6.Sle1.Sle3, which display profound autoreactivity against nuclear self
antigens. The splenocyte proliferation against the two antigens was determined in
the spontaneously autoimmune (NZB * NZW) F1 strain from which other autoimmune
strains used in the study were derived. Immunizations with dH and nH were
attempted in BALB/c mice to assess their splenocyte response. Splenocytes from
BALB/c mice and from autoimmune mice at the time of conversion to autoimmunity
proliferated strongly in response to dH, yet serum IgG from autoimmune (NZB *
NZW) F1, NZM2410, and C57BL/6.Sle1.Sle3 mice displayed a remarkable bias against
binding to dH. At the time of seroconversion, the antibodies already exhibited
preference for nH, and only nH were recovered from circulating immune complexes.
Analysis of histone deimination showed constitutive deimination in thymic
extracts from C57BL/6 and C57BL/6.Sle1.Sle2.Sle3 triply congenic mice and in
spleens of autoimmune triply congenic mice. Our study demonstrates that tolerance
mechanisms against dH are intact in BALB/c and C57BL/6 mice and continue to be
effective in mice with overt autoimmunity to nH. We conclude that, in contrast to
human RA and SLE patients, where we frequently observe autoantibodies against dH,
autoimmune mice maintain strong tolerance mechanisms to prevent the development
of autoantibodies to dH.
PMID- 28424698
TI - Editorial: Immuno-Metabolism in Tumor Microenvironment.
PMID- 28424696
TI - Spirochetal Lipoproteins and Immune Evasion.
AB - Spirochetes are a major threat to public health. However, the exact pathogenesis
of spirochetal diseases remains unclear. Spirochetes express lipoproteins that
often determine the cross talk between the host and spirochetes. Lipoproteins are
pro-inflammatory, modulatory of immune responses, and enable the spirochetes to
evade the immune system. In this article, we review the modulatory effects of
spirochetal lipoproteins related to immune evasion. Understanding lipoprotein
induced immunomodulation will aid in elucidating innate pathogenesis processes
and subsequent adaptive mechanisms potentially relevant to spirochetal disease
vaccine development and treatment.
PMID- 28424697
TI - Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions
with Diverse Ligands and Alterations in Splice Variant Expression.
AB - The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44,
and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and
are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have
classically been defined as activating receptors that trigger cytotoxicity and
cytokine responses by NK cells upon engaging with ligands on tumor cells. Several
new findings, however, have challenged this model and identified alternative
mechanisms regulating the function of NCRs. Recent reports indicate that ligand
matters, since the interaction of NKp44 with distinct ligands on target cells can
either activate or inhibit NK cells. Also, the NCRs have been found to interact
with distinct specificities to various heparan sulfate glycosaminoglycans, which
are complex polysaccharides found in extracellular matrix or on cell surface
heparan sulfate proteoglycans (HSPGs). The NCRs can engage with HSPGs in trans as
a co-ligand on the target cells or in cis on the NK cell surface to regulate
receptor-ligand interactions and NK cell activation. A number of splice variants
of ncr2 and ncr3 have also been identified, and a predominant expression of
certain variants results in inhibitory signaling through NKp44 and NKp30. Several
recent studies have found that the selective expression of some of these
inhibitory splice variants can significantly influence outcome in the contexts of
cancer, infection, and pregnancy. These findings establish that NCR functions are
more diverse than originally thought, and better understanding of their splice
variant expression profiles and ligand interactions are needed to establish their
functional regulation in the context of human health.
PMID- 28424699
TI - Patient's Experience in Pediatric Primary Immunodeficiency Disorders:
Computerized Classification of Questionnaires.
AB - INTRODUCTION: Primary immunodeficiency disorders (PIDs) are a heterogeneous group
of more than 200 rare diseases. Timely diagnosis is of uttermost importance.
Therefore, we aimed to develop a diagnostic questionnaire with computerized
pattern-recognition in order to support physicians to identify suspicious patient
histories. MATERIALS AND METHODS: Standardized interviews were conducted with
guardians of children with PID. The questionnaire based on parental observations
was developed using Colaizzis' framework for content analysis. Answers from 64
PID patients and 62 controls were analyzed by data mining methods in order to
make a diagnostic prediction. Performance was evaluated by k-fold stratified
cross-validation. RESULTS: The diagnostic support tool achieved a diagnostic
sensitivity of up to 98%. The analysis of 12 interviews revealed 26 main
phenomena observed by parents in the pre-diagnostic period. The questions were
systematically phrased and selected resulting in a 36-item questionnaire. This
was answered by 126 patients with or without PID to evaluate prediction. Item
analysis revealed significant questions. DISCUSSION: Our approach proved suitable
for recognizing patterns and thus differentiates between observations of PID
patients and control groups. These findings provide the basis for developing a
tool supporting physicians to consider a PID with a questionnaire. These data
support the notion that patient's experience is a cornerstone in the diagnostic
process.
PMID- 28424700
TI - Grand Challenges in Immunological Memory.
PMID- 28424701
TI - Clinical Overlapping in Autoinflammatory Diseases: The Role of Gene Duplication.
PMID- 28424704
TI - DRACO-STEM: An Automatic Tool to Generate High-Quality 3D Meshes of Shoot Apical
Meristem Tissue at Cell Resolution.
AB - Context: The shoot apical meristem (SAM), origin of all aerial organs of the
plant, is a restricted niche of stem cells whose growth is regulated by a complex
network of genetic, hormonal and mechanical interactions. Studying the
development of this area at cell level using 3D microscopy time-lapse imaging is
a newly emerging key to understand the processes controlling plant morphogenesis.
Computational models have been proposed to simulate those mechanisms, however
their validation on real-life data is an essential step that requires an adequate
representation of the growing tissue to be carried out. Achievements: The tool we
introduce is a two-stage computational pipeline that generates a complete 3D
triangular mesh of the tissue volume based on a segmented tissue image stack.
DRACO (Dual Reconstruction by Adjacency Complex Optimization) is designed to
retrieve the underlying 3D topological structure of the tissue and compute its
dual geometry, while STEM (SAM Tissue Enhanced Mesh) returns a faithful
triangular mesh optimized along several quality criteria (intrinsic quality,
tissue reconstruction, visual adequacy). Quantitative evaluation tools measuring
the performance of the method along those different dimensions are also provided.
The resulting meshes can be used as input and validation for biomechanical
simulations. Availability: DRACO-STEM is supplied as a package of the open-source
multi-platform plant modeling library OpenAlea (http://openalea.github.io/)
implemented in Python, and is freely distributed on GitHub
(https://github.com/VirtualPlants/draco-stem) along with guidelines for
installation and use.
PMID- 28424702
TI - Dual Role of Fas/FasL-Mediated Signal in Peripheral Immune Tolerance.
AB - Fas-mediated apoptosis contributes to physiological and pathological cellular
processes, such as differentiation and survival. In particular, the roles of Fas
in immune cells are complex and critical for the maintenance of immune tolerance.
The precise pathways and unique functions associated with Fas/FasL-mediated
signaling in the immune system are known. The dual character of Fas/FasL-mediated
immune regulation that induces beneficial or harmful effects is associated with
the onset or development of immune disorders. Studies on mutations in genes
encoding Fas and FasL gene of humans and mice contributed to our understanding of
the pathogenesis of autoimmune diseases. Here, we review the opposing functions
of Fas/FasL-mediated signaling, bilateral effects of Fas/FasL on in immune cells,
and complex pathogenesis of autoimmunity mediated by Fas/FasL.
PMID- 28424705
TI - Contemporary Understanding of miRNA-Based Regulation of Secondary Metabolites
Biosynthesis in Plants.
AB - Plant's secondary metabolites such as flavonoids, terpenoids, and alkaloids etc.
are known for their role in the defense against various insects-pests of plants
and for medicinal benefits in human. Due to the immense biological importance of
these phytochemicals, understanding the regulation of their biosynthetic pathway
is crucial. In the recent past, advancement in the molecular technologies has
enabled us to better understand the proteins, enzymes, genes, etc. involved in
the biosynthetic pathway of the secondary metabolites. miRNAs are magical, tiny,
non-coding ribonucleotides that function as critical regulators of gene
expression in eukaryotes. Despite the accumulated knowledge of the miRNA-mediated
regulation of several processes, the involvement of miRNAs in regulating
secondary plant product biosynthesis is still poorly understood. Here, we
summarize the recent progress made in the area of identification and
characterizations of miRNAs involved in regulating the biosynthesis of secondary
metabolites in plants and discuss the future perspectives for designing the
viable strategies for their targeted manipulation.
PMID- 28424703
TI - Immune Responses to Bacillus Calmette-Guerin Vaccination: Why Do They Fail to
Protect against Mycobacterium tuberculosis?
AB - Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is
the current leading cause of death due to a single infectious organism. Although
curable, the broad emergence of multi-, extensive-, extreme-, and total-drug
resistant strains of M.tb has hindered eradication efforts of this pathogen.
Furthermore, computational models predict a quarter of the world's population is
infected with M.tb in a latent state, effectively serving as the largest
reservoir for any human pathogen with the ability to cause significant morbidity
and mortality. The World Health Organization has prioritized new strategies for
improved vaccination programs; however, the lack of understanding of
mycobacterial immunity has made it difficult to develop new successful vaccines.
Currently, Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only vaccine
approved for use to prevent TB. BCG is highly efficacious at preventing meningeal
and miliary TB, but is at best 60% effective against the development of pulmonary
TB in adults and wanes as we age. In this review, we provide a detailed summary
on the innate immune response of macrophages, dendritic cells, and neutrophils in
response to BCG vaccination. Additionally, we discuss adaptive immune responses
generated by BCG vaccination, emphasizing their specific contributions to
mycobacterial immunity. The success of future vaccines against TB will directly
depend on our understanding of mycobacterial immunity.
PMID- 28424706
TI - Evaluation of Yield and Drought Using Active and Passive Spectral Sensing Systems
at the Reproductive Stage in Wheat.
AB - Active and passive sensors are available for ground-based, high-throughput
phenotyping in the field. However, these sensor systems have seldom been compared
with respect to their determination of plant water status and water use
efficiency related parameters under drought conditions. In this study, five
passive and active reflectance sensors, including a hyperspectral passive sensor,
an active flash sensor (AFS), the Crop Circle, and the GreenSeeker, were
evaluated to assess drought-related destructive and non-destructive
morphophysiological parameters (ground cover, relative leaf water content, leaf
temperature, and carbon isotope discrimination of leaves and grain) and grain
yield of twenty wheat (Triticum aestivum L.) cultivars. Measurements were
conducted in a 2-year study, including a drought stress and a control environment
under field conditions. A comparison of the active sensors at the heading,
anthesis and grain-filling stages indicated that the Crop Circle provided the
most significant and robust relationships with drought-related parameters
(relative leaf water content and leaf and grain carbon isotope discrimination).
In comparison with the passive sensor, the five water and normalized water
indices (WI and NWI-1 to 4), which are only provided by the passive sensor,
showed the strongest relationships with the drought stress-related parameters (r
= -0.49 to -0.86) and grain yield (r = -0.88) at anthesis. This paper indicates
that precision phenotyping allows the integration of water indices in breeding
programs to rapidly and cost-effectively identify drought-tolerant genotypes.
This is supported by the fact that grain yield and the water indices showed the
same heritability under drought conditions.
PMID- 28424708
TI - Quantitative Trait Locus Mapping for Verticillium wilt Resistance in an Upland
Cotton Recombinant Inbred Line Using SNP-Based High Density Genetic Map.
AB - Verticillium wilt (VW) caused by Verticillium dahlia Kleb is one of the most
destructive diseases of cotton. Numerous efforts have been made to improve the
resistance of upland cotton against VW, with little progress achieved due to the
paucity of upland cotton breeding germplasms with high level of resistance to VW.
Gossypium barbadense was regarded as more resistant compared to upland cotton;
however, it is difficult to apply the resistance from G. barbadense to upland
cotton improvement because of the hybrid breakdown and the difficulty to fix
resistant phenotype in their interspecific filial. Here we reported QTLs related
to VW resistance identified in upland cotton based on 1 year experiment in
greenhouse with six replications and 4 years investigations in field with two
replications each year. In total, 119 QTLs of disease index (DI) and of disease
incidence (DInc) were identified on 25 chromosome of cotton genome except
chromosome 13 (c13). For DI, 62 QTLs explaining 3.7-12.2% of the observed
phenotypic variations were detected on 24 chromosomes except c11 and c13. For
DInc, 59 QTLs explaining 2.3-21.30% of the observed PV were identified on 19
chromosomes except c5, c8, c12-c13, c18-c19, and c26. Seven DI QTLs were detected
to be stable in at least environments, among which six have sGK9708 alleles,
while 28 DInc QTLs were detected to be stable in at least environments. Eighteen
QTL clusters containing 40 QTLs were identified on 13 chromosomes (c1-c4, c6-c7,
c10, c14, c17 c20-c22, and c24-c25). Most of the stable QTLs aggregated into
these clusters. These QTLs and clusters identification can be an important step
toward Verticillium wilt resistant gene cloning in upland cotton and provide
useful information to understand the complex genetic bases of Verticillium wilt
resistance.
PMID- 28424709
TI - Evolutionary Analysis of Snf1-Related Protein Kinase2 (SnRK2) and Calcium Sensor
(SCS) Gene Lineages, and Dimerization of Rice Homologs, Suggest Deep Biochemical
Conservation across Angiosperms.
AB - Members of the sucrose non-fermenting related kinase Group2 (SnRK2) subclasses
are implicated in both direct and indirect abscisic acid (ABA) response pathways.
We have used phylogenetic, biochemical, and transient in vivo approaches to
examine interactions between Triticum tauschii protein kinase 1 (TtPK1) and an
interacting protein, Oryza sativa SnRK2-calcium sensor (OsSCS1). Given that TtPK1
has 100% identity with its rice ortholog, osmotic stress/ABA-activated protein
kinase (OsSAPK2), we hypothesized that the SCS and TtPK1 interactions are present
in both wheat and rice. Here, we show that SnRK2s are clearly divided into four
pan-angiosperm clades with those in the traditionally defined Subclass II
encompassing two distinct clades (OsSAPK1/2 and OsSAPK3), although OsSAPK3 lacks
an Arabidopsis ortholog. We also show that SCSs are distinct from a second
lineage, that we term SCSsister, and while both clades pre-date land plants, the
SCSsister clade lacks Poales representatives. Our Y2H assays revealed that the
removal of the OsSCS1 C-terminal region along with its N-terminal EF-hand
abolished its interaction with the kinase. Using transient in planta bimolecular
fluorescence complementation experiments, we demonstrate that TtPK1/OsSCS1
dimerization co-localizes with DAPI-stained nuclei and with FM4-64-stained
membranes. Finally, OsSCS1- and OsSAPK2-hybridizing transcripts co-accumulate in
shoots/coleoptile of drying seedlings, consistent with up-regulated kinase
transcripts of PKABA1 and TtPK1. Our studies suggest that interactions between
homologs of the SnRK2 and SCS lineages are broadly conserved across angiosperms
and offer new directions for investigations of related proteins.
PMID- 28424707
TI - New Insights on Leucine-Rich Repeats Receptor-Like Kinase Orthologous
Relationships in Angiosperms.
AB - Leucine-Rich Repeats Receptor-Like Kinase (LRR-RLK) genes represent a large and
complex gene family in plants, mainly involved in development and stress
responses. These receptors are composed of an LRR-containing extracellular domain
(ECD), a transmembrane domain (TM) and an intracellular kinase domain (KD). To
provide new perspectives on functional analyses of these genes in model and non
model plant species, we performed a phylogenetic analysis on 8,360 LRR-RLK
receptors in 31 angiosperm genomes (8 monocots and 23 dicots). We identified 101
orthologous groups (OGs) of genes being conserved among almost all monocot and
dicot species analyzed. We observed that more than 10% of these OGs are absent in
the Brassicaceae species studied. We show that the ECD structural features are
not always conserved among orthologs, suggesting that functions may have diverged
in some OG sets. Moreover, we looked at targets of positive selection footprints
in 12 pairs of OGs and noticed that depending on the subgroups, positive
selection occurred more frequently either in the ECDs or in the KDs.
PMID- 28424710
TI - Identification and Characterization of microRNA319a and Its Putative Target Gene,
PvPCF5, in the Bioenergy Grass Switchgrass (Panicum virgatum).
AB - Due to its high biomass yield, low environmental impact, and widespread
adaptability to poor soils and harsh conditions, switchgrass (Panicum virgatum
L.), a warm-region perennial herbaceous plant, has attracted much attention in
recent years. However, little is known about microRNAs (miRNAs) and their
functions in this bioenergy grass. Here, we identified and characterized a miRNA
gene, Pvi-MIR319a, encoding microRNA319a in switchgrass. Transgenic rice lines
generated by overexpressing the Pvi-MIR319a precursor gene exhibited broader
leaves and delayed flowering compared with the control. Gene expression analysis
indicated at least four putative target genes were downregulated. Additionally,
we cloned a putative target gene (PvPCF5) of Pvi-MIR319a from switchgrass.
PvPCF5, a TCP transcription factor, is a nuclear-localized protein with
transactivation activity and control the development of leaf. Our results suggest
that Pvi-MIR319a and its target genes may be used as potential genetic regulators
for future switchgrass genetic improvement.
PMID- 28424711
TI - Genomic, Molecular Evolution, and Expression Analysis of Genes Encoding Putative
Classical AGPs, Lysine-Rich AGPs, and AG Peptides in Brassica rapa.
AB - Arabinogalactan proteins (AGPs) belong to a class of Pro/Hyp-rich glycoproteins
and are some of the most complex types of macromolecules found in plants. In the
economically important plant species, Brassica rapa, only chimeric AGPs have been
identified to date. This has significantly limited our understanding of the
functional roles of AGPs in this plant. In this study, 64 AGPs were identified in
the genome of B. rapa, including 33 classical AGPs, 28 AG peptides and three lys
rich AGPs. Syntenic gene analysis between B. rapa and A. thaliana suggested that
the whole genome triplication event dominated the expansion of the AGP gene
family in B. rapa. This resulted in a high retained proportion of the AGP family
in the B. rapa genome, especially in the least fractionated subgenome.
Phylogenetic and motif analysis classified the classical AGPs into six clades and
three orphan genes, and the AG peptides into three clades and five orphan genes.
Classical AGPs has a faster rate of molecular evolution than AG peptides revealed
by estimation of molecular evolution rates. However, no significant differences
were observed between classical AGPs and lys-rich AGPs. Under control conditions
and in response to phytohormones treatment, a complete expression profiling
experiment has identified five anther-specific AGPs and quite a number of AGPs
responding to abscisic acid, methyl jasmonate and/or gibberellin. In this study,
we presented a bioinformatics approach to identify important types of AGPs.
Moreover, the association between their function and their protein structure, as
well as the evolution and the expression of AGP genes were investigated, which
might provide fundamental information for revealing the roles of AGPs in B. rapa.
PMID- 28424713
TI - Comprehensive Genomic Identification and Expression Analysis of the Phosphate
Transporter (PHT) Gene Family in Apple.
AB - Elemental phosphorus (Pi) is essential to plant growth and development. The
family of phosphate transporters (PHTs) mediates the uptake and translocation of
Pi inside the plants. Members include five sub-cellular phosphate transporters
that play different roles in Pi uptake and transport. We searched the Genome
Database for Rosaceae and identified five clusters of phosphate transporters in
apple (Malus domestica), including 37 putative genes. The MdPHT1 family contains
14 genes while MdPHT2 has two, MdPHT3 has seven, MdPHT4 has 11, and MdPHT5 has
three. Our overview of this gene family focused on structure, chromosomal
distribution and localization, phylogenies, and motifs. These genes displayed
differential expression patterns in various tissues. For example, expression was
high for MdPHT1;12, MdPHT3;6, and MdPHT3;7 in the roots, and was also increased
in response to low-phosphorus conditions. In contrast, MdPHT4;1, MdPHT4;4, and
MdPHT4;10 were expressed only in the leaves while transcript levels of MdPHT1;4,
MdPHT1;12, and MdPHT5;3 were highest in flowers. In general, these 37 genes were
regulated significantly in either roots or leaves in response to the imposition
of phosphorus and/or drought stress. The results suggest that members of the PHT
family function in plant adaptations to adverse growing environments. Our study
will lay a foundation for better understanding the PHT family evolution and
exploring genes of interest for genetic improvement in apple.
PMID- 28424712
TI - A Functional Approach towards Understanding the Role of the Mitochondrial
Respiratory Chain in an Endomycorrhizal Symbiosis.
AB - Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able
to provide several ecosystem services for crop production. Current economic,
social and legislative contexts should drive the so-called "second green
revolution" by better exploiting these beneficial microorganisms. Many challenges
still need to be overcome to better understand the mycorrhizal symbiosis, among
which (i) the biotrophic nature of AMF, constraining their production, while (ii)
phosphate acts as a limiting factor for the optimal mycorrhizal inoculum
application and effectiveness. Organism fitness and adaptation to the changing
environment can be driven by the modulation of mitochondrial respiratory chain,
strongly connected to the phosphorus processing. Nevertheless, the role of the
respiratory function in mycorrhiza remains largely unexplored. We hypothesized
that the two mitochondrial respiratory chain components, alternative oxidase
(AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal
behavior. For this, a complex approach was developed. At the pre-symbiotic phase
(axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare
spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid
(SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid -
ABA and gibberellic acid - Ga3). At the symbiotic phase, we analyzed phenotypic
and transcriptomic (genes involved in respiration, transport, and fermentation)
responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse
conditions): we monitored the effects driven by ABA, and explored the modulations
induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM
inhibited in vitro spore germination while ABA and Ga3 induced differential spore
germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong
arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA
treated plants, R. irregulare induced down-regulation of StAOX gene isoforms and
up-regulation of genes involved in plant COX pathway. In all phosphorus (P)
concentrations, blocking AOX or COX induced opposite mycorrhizal patterns in
planta: KCN induced higher Arum-type arbuscule density, positive MGD but lower
root colonization compared to SHAM, which favored Paris-type formation and
negative MGD. Following our results and current state-of-the-art knowledge, we
discuss metabolic functions linked to respiration that may occur within
mycorrhizal behavior. We highlight potential connections between AOX pathways and
fermentation, and we propose new research and mycorrhizal application
perspectives.
PMID- 28424714
TI - Relationships between Root Pathogen Resistance, Abundance and Expression of
Pseudomonas Antimicrobial Genes, and Soil Properties in Representative Swiss
Agricultural Soils.
AB - Strains of Pseudomonas that produce antimicrobial metabolites and control
soilborne plant diseases have often been isolated from soils defined as disease
suppressive, i.e., soils, in which specific plant pathogens are present, but
plants show no or reduced disease symptoms. Moreover, it is assumed that
pseudomonads producing antimicrobial compounds such as 2,4-diacetylphloroglucinol
(DAPG) or phenazines (PHZ) contribute to the specific disease resistance of
suppressive soils. However, pseudomonads producing antimicrobial metabolites are
also present in soils that are conducive to disease. Currently, it is still
unknown whether and to which extent the abundance of antimicrobials-producing
pseudomonads is related to the general disease resistance of common agricultural
soils. Moreover, virtually nothing is known about the conditions under which
pseudomonads express antimicrobial genes in agricultural field soils. We present
here results of the first side-by-side comparison of 10 representative Swiss
agricultural soils with a cereal-oriented cropping history for (i) the resistance
against two soilborne pathogens, (ii) the abundance of Pseudomonas bacteria
harboring genes involved in the biosynthesis of the antimicrobials DAPG, PHZ, and
pyrrolnitrin on roots of wheat, and (iii) the ability to support the expression
of these genes on the roots. Our study revealed that the level of soil disease
resistance strongly depends on the type of pathogen, e.g., soils that are highly
resistant to Gaeumannomyces tritici often are highly susceptible to Pythium
ultimum and vice versa. There was no significant correlation between the disease
resistance of the soils, the abundance of Pseudomonas bacteria carrying DAPG,
PHZ, and pyrrolnitrin biosynthetic genes, and the ability of the soils to support
the expression of the antimicrobial genes. Correlation analyses indicated that
certain soil factors such as silt, clay, and some macro- and micronutrients
influence both the abundance and the expression of the antimicrobial genes. Taken
together, the results of this study suggests that pseudomonads producing DAPG,
PHZ, or pyrrolnitrin are present and abundant in Swiss agricultural soils and
that the soils support the expression of the respective biosynthetic genes in
these bacteria to various degrees. The precise role that these pseudomonads play
in the general disease resistance of the investigated agricultural soils remains
elusive.
PMID- 28424715
TI - Temporal Petal Closure Benefits Reproductive Development of Magnolia denudata
(Magnoliaceae) in Early Spring.
AB - The Magnoliaceae shows strong phylogenetic niche conservatism, in which temporal
petal closure has been extensively reported. However, it is yet elusive whether
temporal petal closure is an idle floral character inherited from their ancestors
or an adaptive trait to their habitats. Here, we monitored the process of
temporal floral closure and re-opening in a thermogenic plant, Magnolia denudata
(Magnoliaceae). Furthermore, we artificially interrupted temporal petal closure
and investigated its effects on development of female and male gametophytes.
Intriguingly, we found considerable anatomical changes in the anthers shortly
after temporal closure of petals: disintegration of tapeta, crack of anther
walls, and release of matured pollens. In comparison with normal flowers,
artificially interrupted flowers (no petal closure) showed delayed anther
development and slower pollen germination on stigmas, while little difference in
embryo morphology was observed during the early stage of embryo development.
Moreover, seed set and quality were significantly decreased when petal closure
was prevented. In addition, we found pollination accelerated floral closure in M.
denudata. Taken together, temporal floral closure benefits reproduction of M.
denudata in early spring by promoting anther development and pollen function,
which suggests that it is an adaptive floral trait to its specific habitat.
PMID- 28424716
TI - Growth Stimulatory Effects and Genome-Wide Transcriptional Changes Produced by
Protein Hydrolysates in Maize Seedlings.
AB - Protein hydrolysates are an emerging class of crop management products utilized
for improving nutrient assimilation and mitigating crop stress. They generally
consist of a mixture of peptides and free amino acids derived from the hydrolysis
of plant or animal sources. The present work was aimed at studying the effects
and the action mechanisms of a protein hydrolysate derived from animal residues
on maize root growth and physiology in comparison with the effects induced by
either free amino acids or inorganic N supply. The application of the protein
hydrolysate caused a remarkable enhancement of root growth. In particular, in the
protein hydrolysate-treated plants the length and surface area of lateral roots
were about 7 and 1.5 times higher than in plants treated with inorganic N or free
amino acids, respectively. The root growth promoting effect of the protein
hydrolysate was associated with an increased root accumulation of K, Zn, Cu, and
Mn when compared with inorganic N and amino acids treatments. A microarray
analysis allowed to dissect the transcriptional changes induced by the different
treatments demonstrating treatment-specific effects principally on cell wall
organization, transport processes, stress responses and hormone metabolism.
PMID- 28424717
TI - Expression of the Maize Dof1 Transcription Factor in Wheat and Sorghum.
AB - Nitrogen is essential for plant growth and development. Improving the ability of
plants to acquire and assimilate nitrogen more efficiently is a key agronomic
parameter that will augment sustainability in agriculture. A transcription factor
approach was pursued to address improvement of nitrogen use efficiency in two
major commodity crops. To this end, the Zea mays Dof1 (ZmDof1) transcription
factor was expressed in both wheat (Triticum aestivum) and sorghum (Sorghum
bicolor) either constitutively, UBI4 promoter from sugarcane, or in a tissue
specific fashion via the maize rbcS1 promoter. The primary transcription
activation target of ZmDof1, phosphoenolpyruvate carboxylase (PEPC), is observed
in transgenic wheat events. Expression ZmDof1 under control of the rbcs1 promoter
translates to increase in biomass and yield components in wheat. However,
constitutive expression of ZmDof1 led to the down-regulation of genes involved in
photosynthesis and the functional apparatus of chloroplasts, and an outcome that
negatively impacts photosynthesis, height, and biomass in wheat. Similar patterns
were also observed in sorghum transgenic events harboring the constitutive
expression cassette of ZmDof1. These results indicate that transcription factor
strategies to boost agronomic phenotypic outcomes in crops need to consider
expression patterns of the genetic elements to be introduced.
PMID- 28424718
TI - Comparative Performance of Multivariable Agro-Physiological Parameters for
Detecting Salt Tolerance of Wheat Cultivars under Simulated Saline Field Growing
Conditions.
AB - Field-based trials are crucial for successfully achieving the goals of plant
breeding programs aiming to screen and improve the salt tolerance of crop
genotypes. In this study, simulated saline field growing conditions were designed
using the subsurface water retention technique (SWRT) and three saline irrigation
levels (control, 60, and 120 mM NaCl) to accurately appraise the suitability of a
set of agro-physiological parameters including shoot biomass, grain yield, leaf
water relations, gas exchange, chlorophyll fluorescence, and ion accumulation as
screening criteria to establish the salt tolerance of the salt-tolerant (Sakha
93) and salt-sensitive (Sakha 61) wheat cultivars. Shoot dry weight and grain
yield per hectare were substantially reduced by salinity, but the reduction was
more pronounced in Sakha 61 than in Sakha 93. Increasing salinity stress caused a
significant decrease in the net photosynthesis rate and stomatal conductance of
both cultivars, although their leaf turgor pressure increased. The accumulation
of toxic ions (Na+ and Cl-) was higher in Sakha 61, but the accumulation of
essential cations (K+ and Ca2+) was higher in Sakha 93, which could be the reason
for the observed maintenance of the higher leaf turgor of both cultivars in the
salt treatments. The maximum quantum PSII photochemical efficiency (Fv/Fm) and
the PSII quantum yield (PhiPSII) decreased with increasing salinity levels in
Sakha 61, but they only started to decline at the moderate salinity condition in
Sakha 93. The principle component analysis successfully identified the
interrelationships between all parameters. The parameters of leaf water relations
and toxic ion concentrations were significantly related to each other and could
identify Sakha 61 at mild and moderate salinity levels, and, to a lesser extent,
Sakha 93 at the moderate salinity level. Both cultivars under the control
treatment and Sakha 93 at the mild salinity level were identified by most of the
other parameters. The variability in the angle between the vectors of parameters
explained which parameters could be used as individual, interchangeable, or
supplementary screening criteria for evaluating wheat salt tolerance under
simulated field conditions.
PMID- 28424719
TI - Comparative Analysis of Root Traits and the Associated QTLs for Maize Seedlings
Grown in Paper Roll, Hydroponics and Vermiculite Culture System.
AB - Root system architecture (RSA) plays an important role in the acquisition of both
nitrogen (N) and phosphorus (P) from the environment. Currently RSA is rarely
considered as criteria for selection to improve nutrient uptake efficiency in
crop breeding. Under field conditions roots can be greatly influenced by
uncontrolled environment factors. Therefore, it is necessary to develop fast
selection methods for evaluating root traits of young seedlings in the lab which
can then be related to high nutrient efficiency of adult plants in the field.
Here, a maize recombination inbred line (RILs) population was used to compare the
genetic relationship between RSA and nitrogen and phosphorous efficiency traits.
The phenotypes of eight RSA-related traits were evaluated in young seedlings
using three different growth systems (i.e., paper roll, hydroponics and
vermiculite), and then subjected to correlation analysis with N efficiency and P
efficiency related traits measured under field conditions. Quantitative trait
loci (QTL) of RSA were determined and QTL co-localizations across different
growth systems were further analyzed. Phenotypic associations were observed for
most of RSA traits among all three culture systems. RSA-related traits in
hydroponics and vermiculite weakly correlated with Nitrogen (NupE) uptake
efficiency (r = 0.17-0.31) and Phosphorus (PupE) uptake efficiency (r = 0.22
0.34). This correlation was not found in the paper roll growth system. A total of
14 QTLs for RSA were identified in paper rolls, 18 in hydroponics, and 14 in
vermiculite. Co-localization of QTLs for RSA traits were identified in six
chromosome regions of bin 1.04/1.05, 1.06, 2.04/2.05, 3.04, 4.05, and 5.04/5.05.
The results suggest the problem of using the phenotype from one growth system to
predict those in another growth system. Assessing RSA traits at the seedling
stage using either hydroponics or a vermiculite system appears better suited than
the paper roll system as an important index to accelerate the selection of high N
and P efficient genotypes for maize breeding programs.
PMID- 28424720
TI - Arbuscular Mycorrhizal Fungus Rhizophagus irregularis Increased Potassium Content
and Expression of Genes Encoding Potassium Channels in Lycium barbarum.
AB - Potassium in plants accounts for up to 10% dry weight, and participates in
different physiological processes. Under drought stress, plant requires more
potassium but potassium availability in soil solutes is lowered by decreased soil
water content. Forming symbiosis with arbuscular mycorrhizal (AM) fungi not only
enlarges exploration range of plant for mineral nutrients and water in soil, but
also improves plant drought tolerance. However, the regulation of AM fungi on
plant root potassium uptake and translocation from root to shoot was less
reported. In current study, the effect of an AM fungus (Rhizophagus irregularis),
potassium application (0, 2, and 8 mM), and drought stress (30% field capacity)
on Lycium barbarum growth and potassium status was analyzed. Ten weeks after
inoculation, R. irregularis colonized more than 58% roots of L. barbarum
seedlings, and increased plant growth as well as potassium content. Potassium
application increased colonization rate of R. irregularis, plant growth,
potassium content, and decreased root/shoot ratio. Drought stress increased
colonization rate of R. irregularis and potassium content. Expression of two
putative potassium channel genes in root, LbKT1 and LbSKOR, was positively
correlated with potassium content in root and leaves, as well as the colonization
rate of R. irregularis. The increased L. barbarum growth, potassium content and
genes expression, especially under drought stress, suggested that R. irregularis
could improve potassium uptake of L. barbarum root and translocation from root to
shoot. Whether AM fungi could form a specific mycorrhizal pathway for plant
potassium uptake deserves further studies.
PMID- 28424721
TI - miRNA and Degradome Sequencing Reveal miRNA and Their Target Genes That May
Mediate Shoot Growth in Spur Type Mutant "Yanfu 6".
AB - The spur-type growth habit in apple trees is characterized by short internodes,
increased number of fruiting spurs, and compact growth that promotes flowering
and facilitates management practices, such as pruning. The molecular mechanisms
responsible for regulating spur-type growth have not been elucidated. In the
present study, miRNAs and the expression of their potential target genes were
evaluated in shoot tips of "Nagafu 2" (CF) and spur-type bud mutation "Yanfu 6"
(YF). A total of 700 mature miRNAs were identified, including 202 known apple
miRNAs and 498 potential novel miRNA candidates. A comparison of miRNA expression
in CF and YF revealed 135 differentially expressed genes, most of which were
downregulated in YF. YF also had lower levels of GA, ZR, IAA, and ABA hormones,
relative to CF. Exogenous applications of GA promoted YF shoot growth. Based on
the obtained results, a regulatory network involving plant hormones, miRNA, and
their potential target genes is proposed for the molecular mechanism regulating
the growth of YF. miRNA164, miRNA166, miRNA171, and their potential targets, and
associated plant hormones, appear to regulate shoot apical meristem (SAM) growth.
miRNA159, miRNA167, miRNA396, and their potential targets, and associated plant
hormones appear to regulate cell division and internode length. This study
provides a foundation for further studies designed to elucidate the mechanism
underlying spur-type apple architecture.
PMID- 28424722
TI - The Role of Auxin-Ethylene Crosstalk in Orchestrating Primary Root Elongation in
Sugar Beet.
AB - It is well-established in Arabidopsis and other species that ethylene inhibits
root elongation through the action of auxin. In sugar beet (Beta vulgaris L.)
ethylene promotes root elongation in a concentration dependent manner. However,
the crosstalk between ethylene and auxin remains unknown during sugar beet
seedling development. Our experiments have shown that exogenously applied auxin
(indole-3-acetic acid; IAA) also stimulates root elongation. We also show that
auxin promotes ethylene biosynthesis leading to longer roots. We have further
demonstrated that the auxin treatment stimulates ethylene production by
redirecting the pool of available 1-aminocyclopropane-1-carboxylic acid (ACC)
toward ethylene instead of malonyl-ACC (MACC) resulting in a prolonged period of
high rates of ethylene production and subsequently a longer root. On the other
hand we have also shown that endogenous IAA levels were not affected by an ACC
treatment during germination. All together our findings suggest that the general
model for auxin-ethylene crosstalk during early root development, where ethylene
controls auxin biosynthesis and transport, does not occur in sugar beet. On the
contrary, we have shown that the opposite, where auxin stimulates ethylene
biosynthesis, is true for sugar beet root development.
PMID- 28424723
TI - Evidence, Mechanism and Alternative Chemical Seedbank-Level Control of Glyphosate
Resistance of a Rigid Ryegrass (Lolium rigidum) Biotype from Southern Spain.
AB - Rigid ryegrass (Lolium rigidum) is one of the most troublesome weeds in different
crops in the Mediterranean region. A rigid ryegrass biotype from an olive grove
in Jaen province (Andalusia, southern Spain), potentially resistant to glyphosate
(RG), was tested for its resistance level through dose-response assays using a
susceptible biotype (SG). To test the hypothesis of a non-target-site-based
resistance, as point mutations are far less common mechanisms of glyphosate
resistance, studies were also conducted to elucidate whether resistance was
associated with biochemical, metabolism, molecular and/or physiological
mechanisms. Alternative herbicide-based control options, including single
herbicide or herbicide mixtures with glyphosate, applied at seedling, tillering
or full heading stages, were tested in field experiments for 2 years for their
efficacy against rigid ryegrass plants and their effects on the soil seed bank.
Resistance levels of the RG biotype were 23- (LD50) and 7-fold (GR50) higher
compared to the SG biotype. The SG biotype exhibited a significantly greater
shikimic acid accumulation than the RG one. At 96 HAT, 58 and 89% of applied 14C
glyphosate was up taken by leaves of RG and SG biotype plants, respectively, and,
at this time, a significantly higher proportion of the glyphosate taken up by the
treated leaf remained in its tissue in RG plants compared to the SG ones. The RG
biotype did not reveal any point mutation in the glyphosate target site EPSP
synthase. Overall, results confirmed reduced glyphosate uptake and translocation
as being the mechanism involved in glyphosate resistance in the RG biotype. RG
biotype responses to the alternative treatments tested in situ indicated that
herbicide applications at the later growth stage tended to be less effective in
terms of immediate effects on population size than earlier applications, and that
only in some cases, the removal of at least 85% of the RG biotype was achieved.
However, with few exceptions, the alternative treatments tested appeared to be
highly effective in reducing the seed bank irrespective of the growth stage. The
frequency of the resistant phenotype in the progeny of surviving plants of the RG
biotype was dependent on treatment. Results suggest that a potential exists for
effective management of glyphosate-resistant rigid ryegrass in olive groves in
southern Spain.
PMID- 28424724
TI - Soluble Starch Synthase III-1 in Amylopectin Metabolism of Banana Fruit:
Characterization, Expression, Enzyme Activity, and Functional Analyses.
AB - Soluble starch synthase (SS) is one of the key enzymes involved in amylopectin
biosynthesis in plants. However, no information is currently available about this
gene family in the important fruit crop banana. Herein, we characterized the
function of MaSSIII-1 in amylopectin metabolism of banana fruit and described the
putative role of the other MaSS family members. Firstly, starch granules, starch
and amylopectin content were found to increase during banana fruit development,
but decline during storage. The SS activity started to increase later than
amylopectin and starch content. Secondly, four putative SS genes were cloned and
characterized from banana fruit. Among them, MaSSIII-1 showed the highest
expression in banana pulp during fruit development at transcriptional levels.
Further Western blot analysis suggested that the protein was gradually increased
during banana fruit development, but drastically reduced during storage. This
expression pattern was highly consistent with changes in starch granules,
amylopectin content, and SS activity at the late phase of banana fruit
development. Lastly, overexpression of MaSSIII-1 in tomato plants distinctly
changed the morphology of starch granules and significantly increased the total
starch accumulation, amylopectin content, and SS activity at mature-green stage
in comparison to wild-type. The findings demonstrated that MaSSIII-1 is a key
gene expressed in banana fruit and responsible for the active amylopectin
biosynthesis, this is the first report in a fresh fruit species. Such a finding
may enable the development of molecular markers for banana breeding and genetic
improvement of nutritional value and functional properties of banana fruit.
PMID- 28424726
TI - Size-Mediated Interaction between a Cushion Species and Other Non-cushion Species
at High Elevations of the Hengduan Mountains, SW China.
AB - Arenaria polytrichoides (Caryophyllaceae) is a common cushion plant occurring at
high elevations in the Himalaya-Hengduan Mountains, SW China. It frequently has
other non-cushion species growing within its canopy, forming a contrast with the
surrounding areas because it creates patches of higher diversity and greater
biomass. In this study, we examined the relationship between the cushions and
associated non-cushion species along a gradient of cushion size. A total of 200
A. polytrichoides individuals were selected to fit four size classes. Field
measurements were carried out to assess canopy structure, functional traits
relevant to growth and reproduction, and soil quality below cushions along the
size gradient. Furthermore, the size effect of cushions on the richness and
abundance of species and biomass production was also examined. All the
morphological variables examined exhibited a positive correlation with cushion
size, as did the nutrients under cushions. Large and compact cushions were
associated with higher soil nutrient contents compared with small and loose
cushions. As a result of these biogenic environmental changes, there was a
stronger facilitation effect performed by large cushions. Data pertaining to
functional traits revealed that large cushions benefit from the enhanced
resources within their compact structure and exhibit greater fitness and a higher
reproductive output than small cushions. Our data indicated that interactions
occur between cushion species and other plants depending on the size of the
cushions, probably because of the greater heterogeneity of conditions beneath
larger cushions. These findings provide a clear demonstration of the generally
overlooked importance of the traits of nurse plants, such as size and age, in
terms of their facilitative effects.
PMID- 28424725
TI - A Genome-Scale Analysis of the PIN Gene Family Reveals Its Functions in Cotton
Fiber Development.
AB - The PIN-FORMED (PIN) protein, the most important polar auxin transporter, plays a
critical role in the distribution of auxin and controls multiple biological
processes. However, characterizations and functions of this gene family have not
been identified in cotton. Here, we identified the PIN family in Gossypium
hirsutum, Gossypium arboreum, and Gossypium raimondii. This gene family was
divided into seven subgroups. A chromosomal distribution analysis showed that
GhPIN genes were evenly distributed in eight chromosomes and that the whole
genome and dispersed duplications were the main duplication events for GhPIN
expansion. qRT-PCR analysis showed a tissue-specific expression pattern for
GhPIN. Likely due to the cis-element variations in their promoters, transcripts
of PIN6 and PIN8 genes from the At (tetraploid genome orginated from G. arboreum)
subgenome and PIN1a from the Dt (tetraploid genome orginated from G. raimondii)
subgenome in G. hirsutum was significantly increased compared to the transcripts
in the diploids. The differential regulation of these PIN genes after the
polyploidization may be conducive to fiber initiation and elongation. Exogenously
applied auxin polar transport inhibitor significantly suppressed fiber growth,
which is consistent with the essential function of these PIN genes for regulating
cotton fiber development. Furthermore, the overexpression of GhPIN1a_Dt,
GhPIN6_At, and GhPIN8_At in Arabidopsis promoted the density and length of
trichomes in leaves.
PMID- 28424727
TI - Host-Induced Silencing of Two Pharyngeal Gland Genes Conferred Transcriptional
Alteration of Cell Wall-Modifying Enzymes of Meloidogyne incognita vis-a-vis
Perturbed Nematode Infectivity in Eggplant.
AB - The complex parasitic strategy of Meloidogyne incognita appears to involve
simultaneous expression of its pharyngeal gland-specific effector genes in order
to colonize the host plants. Research reports related to effector crosstalk in
phytonematodes for successful parasitism of the host tissue is yet underexplored.
In view of this, we have used in planta effector screening approach to understand
the possible interaction of pioneer genes (msp-18 and msp-20, putatively involved
in late and early stage of M. incognita parasitism, respectively) with other
unrelated effectors such as cell-wall modifying enzymes (CWMEs) in M. incognita.
Host-induced gene silencing (HIGS) strategy was used to generate the transgenic
eggplants expressing msp-18 and msp-20, independently. Putative transformants
were characterized via qRT-PCR and Southern hybridization assay. SiRNAs specific
to msp-18 and msp-20 were also detected in the transformants via Northern
hybridization assay. Transgenic expression of the RNAi constructs of msp-18 and
msp-20 genes resulted in 43.64-69.68% and 41.74-67.30% reduction in M. incognita
multiplication encompassing 6 and 10 events, respectively. Additionally,
transcriptional oscillation of CWMEs documented in the penetrating and developing
nematodes suggested the possible interaction among CWMEs and pioneer genes. The
rapid assimilation of plant-derived carbon by invading nematodes was also
demonstrated using 14C isotope probing approach. Our data suggests that HIGS of
msp-18 and msp-20, improves nematode resistance in eggplant by affecting the
steady-state transcription level of CWME genes in invading nematodes, and
safeguard the plant against nematode invasion at very early stage because
nematodes may become the recipient of bioactive RNA species during the process of
penetration into the plant root.
PMID- 28424728
TI - Landscape Population Genomics of Forsythia (Forsythia suspensa) Reveal That
Ecological Habitats Determine the Adaptive Evolution of Species.
AB - Understanding the genetic mechanisms of adaptation to environmental variables is
a key concern in molecular ecology and evolutionary biology. Determining the
adaptive evolutionary direction and evaluating the adaptation status of species
can improve our understanding of these mechanisms. In this study, we sampled 20
populations of Forsythia suspensa to infer the relationship between environmental
variables and adaptive genetic variations. Population structure analysis revealed
that four genetic groups of F. suspensa exist resulting from divergent selection
driven by seven environmental variables. A total of 26 outlier loci were
identified by both BayeScan and FDIST2, 23 of which were environment-associated
loci (EAL). Environmental association analysis revealed that the environmental
variables related to the ecological habitats of F. suspensa are associated with
high numbers of EAL. Results of EAL characterization in F. suspensa are
consistent with the hypothesis that ecological habitats determine the adaptive
evolution of this species. Moreover, a model of species adaptation to
environmental variables was proposed in this study. The adaptation model was used
to further evaluate the adaptation status of F. suspensa to environmental
variables. This study will be useful to help us in understanding the adaptive
evolution of species in regions lacking strong selection pressure.
PMID- 28424729
TI - Genome-Wide Identification and Analyses of Calmodulins and Calmodulin-like
Proteins in Lotus japonicas.
AB - L. japonicus, a model plant of legumes plants, is widely used in symbiotic
nitrogen fixation. A large number of studies on it have been published based on
the genetic, biochemical, structural studies. These results are secondhand
reports that CaM is a key regulator during Rhizobial infection. In plants, there
are multiple CaM genes encoding several CaM isoforms with only minor amino acid
differences. Moreover, the regulation mechanism of this family of proteins during
rhizobia infection is still unclear. In the current study, a family of genes
encoding CaMs and CMLs that possess only the Ca2+-binding EF-hand motifs were
analyzed. Using ML and BI tree based on amino acid sequence similarity, seven
loci defined as CaMs and 19 CMLs, with at least 23% identity to CaM, were
identified. The phylogenetics, gene structures, EF hand motif organization, and
expression characteristics were evaluated. Seven CaM genes, encoding only 4
isoforms, were found in L. japonicus. According to qRT-PCR, four LjCaM isoforms
are involved in different rhizobia infection stages. LjCaM1 might be involved in
the early rhizobia infection epidermal cells stage. Furthermore, additional
structural differences and expression behaviors indicated that LjCMLs may have
different potential functions from LjCaMs.
PMID- 28424730
TI - Melatonin Improves Waterlogging Tolerance of Malus baccata (Linn.) Borkh.
Seedlings by Maintaining Aerobic Respiration, Photosynthesis and ROS Migration.
AB - Waterlogging, one of the notorious abiotic stressors, retards the growth of apple
plants and reduces their production. Thus, it is an urgent agenda for scientists
to identify the suitable remedies for this problem. In the current study, we
found that melatonin significantly improved the tolerance of apple seedlings
against waterlogging stress. This was indicated by the reduced chlorosis and
wilting of the seedlings after melatonin applications either by leaf spray or
root irrigation. The mechanisms involve in that melatonin functions to maintain
aerobic respiration, preserves photosynthesis and reduces oxidative damage of the
plants which are under waterlogging stress. Melatonin application also enhances
the gene expression of its synthetic enzymes (MbT5H1, MbAANAT3, MbASMT9) and
increases melatonin production. This is the first report of a positive feedback
that exogenous melatonin application promotes the melatonin synthesis in plants.
A post-transcriptional regulation apparently participated in this regulation.
When exogenous melatonin meets the requirement of the plants it is found that the
protein synthesis of MbASMT9 was suppressed. Taken together, the results showed
that melatonin was an effective molecule to protect plant, particularly apple
plant, against waterlogging stress.
PMID- 28424731
TI - Identification of TIFY Family Genes and Analysis of Their Expression Profiles in
Response to Phytohormone Treatments and Melampsora larici-populina Infection in
Poplar.
AB - The TIFY domain contains approximately 36 conserved amino acids that form the
core motif TIF[F/Y]XG, and they were reported to play important roles in plant
growth, tissue development and defense regulation. Moreover, more and more
evidence has shown that some members of the TIFY gene family perform their
functions by modulating plant hormone signaling pathways. Poplar trees are found
worldwide, and they comprise approximately 30 species. Benefit from the
importance of poplar and its advanced platform, this tree is considered to be the
model perennial plant. Here, we conducted a genome-wide identification of TIFY
genes in poplar, and 24 TIFY genes were found. These 24 TIFY genes were assigned
to different subfamilies according to the presence or absence of domains and
motifs that they harbored. Careful analyses of their locations, structures,
evolution and duplication patterns revealed an overview of this gene family in
poplar. The expression profiles of these 24 TIFY genes were then analyzed in
different tissues using publicly available expression data; their expression
profiles following different JA/SA treatments and infection with leaf rust
pathogen were also carefully examined by qRT-PCR assays. Based on their
expression profiles, the functions of a number of TIFY genes could be predicted.
By performing this study, we have provided valuable information for further
functional characterisation of TIFY genes in poplar and candidate genes for the
improvement of poplar disease resistance.
PMID- 28424732
TI - Evidence for Loss in Identity, De-Differentiation, and Trans-Differentiation of
Islet beta-Cells in Type 2 Diabetes.
AB - The two main types of diabetes mellitus have distinct etiologies, yet a similar
outcome: loss of islet beta-cell function that is solely responsible for the
secretion of the insulin hormone to reduce elevated plasma glucose toward
euglycemic levels. Type 1 diabetes (T1D) has traditionally been characterized by
autoimmune-mediated beta-cell death leading to insulin-dependence, whereas type 2
diabetes (T2D) has hallmarks of peripheral insulin resistance, beta-cell
dysfunction, and cell death. However, a growing body of evidence suggests that,
especially during T2D, key components of beta-cell failure involves: (1) loss of
cell identity, specifically proteins associated with mature cell function (e.g.,
insulin and transcription factors like MAFA, PDX1, and NKX6.1), as well as (2) de
differentiation, defined by regression to a progenitor or stem cell-like state.
New technologies have allowed the field to compare islet cell characteristics
from normal human donors to those under pathophysiological conditions by single
cell RNA-Sequencing and through epigenetic analysis. This has revealed a
remarkable level of heterogeneity among histologically defined "insulin-positive"
beta-cells. These results not only suggest that these beta-cell subsets have
different responses to insulin secretagogues, but that defining their unique gene
expression and epigenetic modification profiles will offer opportunities to
develop cellular therapeutics to enrich/maintain certain subsets for correcting
pathological glucose levels. In this review, we will summarize the recent
literature describing how beta-cell heterogeneity and plasticity may be
influenced in T2D, and various possible avenues of therapeutic intervention.
PMID- 28424734
TI - Influence of Teeth Preparation Finishing on the Adaptation of Lithium Disilicate
Crowns.
AB - The polishing step of teeth preparations for crowns is a step often performed, so
that there is an increased time during the clinical procedure. The aim of this
study is to evaluate the marginal and internal adaptation of all-ceramic CAD/CAM
lithium disilicate crowns in polished preparations for crown and nonpolished
preparations for crowns. For this purpose, 20 first molars were selected, which
were divided into two groups (n = 10) G1, teeth that received surface roughening
similar to preparation without polishing, and G2 (control), polished
preparations. After the preparations were completed the teeth were scanned (Cerec
Bluecam, Sirona, Bensheim, Germany), and the crowns were designed and machined
using CAD/CAM technology (Sirona, Bensheim, Germany). The adaptation of the
pieces was evaluated using polyvinyl siloxane replicas and stereomicroscope
photographs with 70x magnifications. The normality test indicated a nonnormal
result, so a Man-Whitney nonparametric test was performed. One out of the 24
measured regions showed a statistically significant difference (p = 0.0494). With
this study it can be concluded that crowns fabricated by CAD/CAM technology
performed on unpolished preparations are not influenced by the internal marginal
adaptation and the ceramic part and are different from polished preparations.
PMID- 28424733
TI - Combined Implant and Tooth Support: An Up-to-Date Comprehensive Overview.
AB - Objectives. This article presents a review on the concerned topics and some
considerations related to the concept of splinting teeth and implants in the
rehabilitation of partial edentulism. Study Selection. An electronic
PubMed/MEDLINE and manual search of identified articles and reviews as well as
clinical, laboratory, and finite element studies was performed in this project.
Due to the shortage in within-subject, long term, randomized, controlled clinical
trials regarding the subject a meta-analysis was not possible. Results. Although
surrounded with some controversy, joining teeth and implants during the
rehabilitation of partial edentulism provides the clinicians with more treatment
options where proprioception and bone volume are maintained and distal
cantilevers and free end saddles are eliminated. It makes the treatment less
complex, of less cost, and more acceptable for the patient. Conclusions. Whenever
suitable and justified, combining implant and tooth support might be recommended
as an alternative during rehabilitation of partial edentulism. Based on the
literature, clinical tips and suggestions were recommended to increase the
success of this treatment.
PMID- 28424735
TI - Tongue Necrosis Secondary to Giant Cell Arteritis: A Case Report and Literature
Review.
AB - Giant cell arteritis is a form of vasculitis involving the medium- and large
sized arteries that chiefly affects older people. Clinical findings are headache,
jaw claudication, fever, pain, and thickening of the temporal artery. The most
feared complication is visual loss due to impairment of the ophthalmic artery and
posterior ciliary arteries. This a case report of an 85-year-old male presenting
with headache and jaw pain, who was admitted with tongue necrosis as an initial
manifestation of giant cell arteritis. The necrotic area detached spontaneously
after two weeks of therapy with corticosteroids and methotrexate. Reviewing the
literature, our patient presented with clinical symptoms consistent with most
reports, except for the fact of being male. Although unusual as an initial
manifestation, tongue necrosis is an important alert for diagnosing giant cell
arteritis. Early diagnosis and treatment of this atypical manifestation may
reduce morbidity.
PMID- 28424736
TI - A Case of Xanthogranulomatous Pyelonephritis Associated with Renoduodenal
Fistula.
AB - Xanthogranulomatous pyelonephritis (XGP) is a rare form of pyelonephritis
associated with repeated infection, chronic inflammation, and obstruction.
Various fistulas, including those to the intestine, are a known association with
XGP. Here, a 55-year-old woman with a history of multiple previous renal calculi
presented with dysuria and back pain. Contrast-enhanced computed tomography (CT)
revealed a soft tissue density in her renal pelvis and perirenal space consistent
with XGP along with a tract connecting the upper pole of her right kidney to the
second portion of the duodenum. This finding was subsequently confirmed during
percutaneous nephrostomy placement, stent placement, a small bowel follow-through
study, and upper endoscopy. She was diagnosed with XGP with associated
renoduodenal fistula, eventually treated by open nephrectomy with fistula
takedown. Histopathologic analysis was consistent with the diagnosis of XGP with
no malignant or infectious cause of the fistula. XGP should be considered in the
diagnosis of patients with dysuria and back pain, especially when a history of
obstruction or chronic inflammation. Associated fistulas should also be
considered prior to surgical management to prevent complications.
PMID- 28424737
TI - GC-MS Based Metabolite Profiling, Antioxidant and Antimicrobial Properties of
Different Solvent Extracts of Malaysian Plectranthus amboinicus Leaves.
AB - This study evaluates the phytochemistry, antioxidant, and antimicrobial effects
of Plectranthus amboinicus leaves extracted in different solvents. The methanol
extract contained the highest total phenolic (94.37 +/- 1.24 mg GAE/g) and
flavonoid contents (26.90 +/- 1.35 mg RE/g) and exhibited the highest DPPH
scavenging activity (90.13 +/- 3.32%) followed by the acetone extract (80.23 +/-
3.26%) at 500 MUg/mL concentration. Similarly, the highest ferric ion reduction
potential (849.63 +/- 30.95 MUM of Fe (II)/g dry weight) was exhibited by the
methanol extract followed by the acetone extract (695.92 +/- 25.44 MUM of Fe
(II)/g dry weight). The methanol extract showed greater antimicrobial activity
against all the tested pathogens (Bacillus subtilis, Methicillin-resistant
Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida
albicans). However, both hexane and acetone extracts failed to inhibit E. coli.
S. aureus and C. albicans were more susceptible to all the extracts. Further, GC
MS analysis confirmed the occurrence of a total 46 phytocompounds in different
solvent extracts. Some of the major compounds included carvacrol (37.7%),
tetracontane (16.6%), squalene (15.6%), tetrapentacontane (13.7%), and Phytol
(12.9%). In conclusion, extraction solvents influenced the recovery of
phytocompounds and the highest pharmacological activities of the methanol extract
could be correlated to the presence of additional bioactive compounds.
PMID- 28424738
TI - Protective Effects of Li-Fei-Xiao-Yan Prescription on Lipopolysaccharide-Induced
Acute Lung Injury via Inhibition of Oxidative Stress and the TLR4/NF-kappaB
Pathway.
AB - Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat
inflammatory and infectious diseases including inflammatory lung diseases. The
present study was aimed at evaluating the potential therapeutic effects and
potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-)
induced acute lung injury (ALI). In this study, the mice were orally pretreated
with LFXY or dexamethasone (positive drug) before the intratracheal instillation
of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate
of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung
histopathology impairment, suppressed the excessive inflammatory responses via
decreasing the expression of proinflammatory cytokines (TNF-alpha, IL-1beta, and
IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and
repressed oxidative stress through the inhibition of MPO and MDA contents and the
upregulation of antioxidants (SOD and GSH) activities. Mechanistically, treatment
with LFXY significantly prevented LPS-induced TLR4 expression and NF-kappaB (p65)
phosphorylation. Overall, the present study suggests that LFXY protected mice
from acute lung injury induced by LPS via inhibition of TLR4/NF-kappaB p65
activation and upregulation of antioxidative enzymes and it may be a potential
preventive and therapeutic agent for ALI in the clinical setting.
PMID- 28424739
TI - Rapid Screening of Potential Phosphodiesterase Inhibitors from the Roots of Ilex
pubescens Hook. et Arn. Using a Combination of Ultrafiltration and LC-MS.
AB - The cyclic nucleotide phosphodiesterase (PDE) plays an important role in
regulating the levels of second messenger molecules cAMP and cGMP. Various PDE
inhibitors have been successfully developed into drugs for targeted diseases. In
addition, PDE inhibitors can also be found in different foods and natural
medicines. In this study, ultrafiltration liquid chromatography-diode-array
detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry
(ultrafiltration LC-DAD-ESI-IT-TOF-MS) was applied to screen PDE inhibitors from
the roots of Ilex pubescens Hook. et Arn. As a result, 11 major compounds were
identified in I. pubescens roots, with nine compounds as potential PDE
inhibitors, among which five were further confirmed to be active against PDEI and
PDE5A dose-dependently in vitro, with ilexsaponin A1 and ilexsaponin B2 being the
strongest. HPLC quantification of these bioactive compounds suggested that they
are major components in the plant. The results demonstrate that ultrafiltration
LC-DAD-ESI-IT-TOF-MS is an efficient method for rapid screening of PDE inhibitors
from natural medicines.
PMID- 28424740
TI - Essential role of long non-coding RNAs in de novo chromatin modifications: the
genomic address code hypothesis.
AB - The epigenome, i.e., the whole of chromatin modifications, is transferred from
mother to daughter cells during cell differentiation. When de novo chromatin
modifications (establishment or erasure of, respectively, new or pre-existing DNA
methylations and/or histone modifications) are made in a daughter cell, however,
it has a different epigenome than its mother cell. Although de novo chromatin
modification is an important event that comprises elementary processes of cell
differentiation, its molecular mechanism remains poorly understood. We argue, in
this letter, that a key to solving this problem lies in understanding the role of
long non-coding RNAs (lncRNAs), a type of RNA that is becoming increasingly
prominent in epigenetic studies. Many studies show that lncRNAs form
ribonucleoprotein complexes in the nucleus and are involved in chromatin
modifications. However, chromatin-modifying enzymes lack the information about
genomic positions on which they act. It is known, on the other hand, that a
single-stranded RNA in general can bind to a double-stranded DNA to form a triple
helix. If each lncRNA forms a ribonucleoprotein complex with chromatin-modifying
enzymes on one hand and, at the same time, a triple helix with a genomic region
based on its specific nucleotide sequence on the other hand, it can induce de
novo chromatin modifications at specific sites. Thus, the great variety of
lncRNAs can be explained by the requirement for the diversity of "genomic address
codes" specific to their cognate genomic regions where de novo chromatin
modifications take place.
PMID- 28424742
TI - FRET from single to multiplexed signaling events.
AB - Forster resonance energy transfer (FRET) is a powerful tool for the visualization
of molecular signaling events such as protein activities and interactions in
cells. In its different implementations, FRET microscopy has been mainly used for
monitoring single events. Recently, there has been a trend of extending FRET
imaging towards the simultaneous detection of multiple events and interactions.
The concomitant increase in experimental complexity requires a deeper
understanding of the biophysical background of FRET. The presence of multiple
acceptors for one donor affects the well-known formalism for FRET between two
molecules, increasing distance sensitivity through mechanisms that have become
known as the 'antenna' and 'surplus' effect. We will discuss the nature of these
effects and present the imaging methods that have been used to unravel the
combined transfer rates in the multi-protein interactions of multiplexed FRET
experiments. Multiplexing strategies are becoming invaluable analytical tools for
the elucidation of biological complexes and for the visualization of decision
points in cellular signaling networks in physiological and pathological
conditions.
PMID- 28424741
TI - Catalytic robustness and torque generation of the F1-ATPase.
AB - The F1-ATPase is the catalytic portion of the FoF1 ATP synthase and acts as a
rotary molecular motor when it hydrolyzes ATP. Two decades have passed since the
single-molecule rotation assay of F1-ATPase was established. Although several
fundamental issues remain elusive, basic properties of F-type ATPases as motor
proteins have been well characterized, and a large part of the reaction scheme
has been revealed by the combination of extensive structural, biochemical,
biophysical, and theoretical studies. This review is intended to provide a
concise summary of the fundamental features of F1-ATPases, by use of the well
described model F1 from the thermophilic Bacillus PS3 (TF1). In the last part of
this review, we focus on the robustness of the rotary catalysis of F1-ATPase to
provide a perspective on the re-designing of novel molecular machines.
PMID- 28424743
TI - Towards Bi-Inclusive Policies: Suggestions Based on Research on Dutch Same-Sex
Attracted Young People.
AB - Dutch national LGBT policies are not bi-inclusive and this study provides
suggestions for improvement, based on empirical research. Attention for
bisexuality in policy appears simply to pay lip service and to endorse the
construction of sexual orientation as a hetero/homo binary. The outcomes of our
survey (n = 1449) and in-depth interviews (n = 38) of Dutch same-sex attracted
young people suggest that special attention for bisexual people is warranted.
Compared to exclusively same-sex attracted participants, the equally both-sex
attracted participants scored worse on openness about their sexual attraction,
visibility discomfort, perceived acceptance, and suicide attempts. Unique issues
for bisexual-identified young people were identified as follows: marginalization
of bisexuality; difficulty expressing bisexuality, particularly in relationships;
and a lack of bisexual or bi-inclusive communities. These issues were all related
to the hetero/homo binary and mononormativity. Suggested implications for more bi
inclusive policies focus on awareness of marginalization and invisibility of
bisexuality, biphobia, community and capacity building, and comprehensive
sexuality and gender education. Furthermore, rather than policies focusing on
sameness, a comprehensive diversity perspective on sexuality and gender offers
more space for bisexuality. This may be particularly relevant for young people
who are exploring their sexuality and developing a sense of their sexual self.
PMID- 28424744
TI - Oxidative Stress in Retinal Diseases.
PMID- 28417000
TI - hackseq: Catalyzing collaboration between biological and computational scientists
via hackathon.
AB - hackseq ( http://www.hackseq.com) was a genomics hackathon with the aim of
bringing together a diverse set of biological and computational scientists to
work on collaborative bioinformatics projects. In October 2016, 66 participants
from nine nations came together for three days for hackseq and collaborated on
nine projects ranging from data visualization to algorithm development. The
response from participants was overwhelmingly positive with 100% (n = 54) of
survey respondents saying they would like to participate in future hackathons. We
detail key steps for others interested in organizing a successful hackathon and
report excerpts from each project.
PMID- 28424745
TI - Distinguishing the Unique Neuropathological Profile of Blast Polytrauma.
AB - Traumatic brain injury sustained after blast exposure (blast-induced TBI) has
recently been documented as a growing issue for military personnel. Incidence of
injury to organs such as the lungs has decreased, though current epidemiology
still causes a great public health burden. In addition, unprotected civilians
sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to
moderate cases of PBLI are survivable with medical intervention, which creates a
growing population of survivors of blast-induced polytrauma (BPT) with symptoms
from blast-induced mild TBI (mTBI). Currently, there is a lack of preclinical
models simulating BPT, which is crucial to identifying unique injury mechanisms
of BPT and its management. To meet this need, our group characterized a rodent
model of BPT and compared results to a blast-induced mTBI model. Open field (OF)
performance trials were performed on rodents at 7 days after injury.
Immunohistochemistry was performed to evaluate cellular outcome at day seven
following BPT. Levels of reactive astrocytes (GFAP), apoptosis (cleaved caspase-3
expression), and vascular damage (SMI-71) were significantly elevated in BPT
compared to blast-induced mTBI. Downstream markers of hypoxia (HIF-1alpha and
VEGF) were higher only after BPT. This study highlights the need for unique
therapeutics and prehospital management when handling BPT.
PMID- 28424747
TI - Association between Optic Nerve Head Microcirculation and Macular Ganglion Cell
Complex Thickness in Eyes with Untreated Normal Tension Glaucoma and a Hemifield
Defect.
AB - Purpose. We evaluated the association between optic nerve head (ONH)
microcirculation and macular ganglion cell complex (mGCC) thickness in patients
with untreated normal tension glaucoma (NTG) and a hemifield defect. Methods. The
medical records of 47 patients with untreated NTG were retrospectively reviewed.
Laser speckle flowgraphy was used to obtain mean blur rate (MBR), a relative
measure of blood flow. Average total deviation (TD), mGCC, and the
circumpapillary retinal nerve fiber layer (cpRNFL) thickness were also analyzed.
Results. All parameters corresponding to the defective hemifield were
significantly lower than those corresponding to the normal hemifield. In the
defective hemifield, MBR was correlated with TD, mGCC, and cpRNFL thickness. In
the normal hemifield, MBR was only correlated with mGCC thickness, and multiple
regression analysis showed that mGCC thickness was a significant contributing
factor of the MBR. Conclusion. MBR was well correlated with mGCC thickness in
eyes with untreated NTG and a hemifield defect. In the normal hemifield, mGCC
thickness was a contributing factor of the MBR indicating that ONH circulatory
dysfunction may be associated with retinal structural changes in the early stages
of glaucoma. A reduction in ONH microcirculation may be an early indicator of the
presence and progression of glaucoma.
PMID- 28424748
TI - Immigrant Arrival and Tuberculosis among Large Immigrant- and Refugee-Receiving
Countries, 2005-2009.
AB - Objective. Tuberculosis control in foreign-born populations is a major public
health concern for Australia, Canada, New Zealand, United Kingdom, and the United
States, large immigrant- and refugee-receiving countries that comprise the
Immigration and Refugee Health Working Group (IRHWG). Identifying and comparing
immigration and distribution of foreign-born tuberculosis cases are important for
developing targeted and collaborative interventions. Methods. Data stratified by
year and country of birth from 2005 to 2009 were received from these five
countries. Immigration totals, tuberculosis case totals, and multidrug-resistant
tuberculosis (MDR TB) case totals from source countries were analyzed and
compared to reveal similarities and differences for each member of the group.
Results. Between 2005 and 2009, there were a combined 31,785,002 arrivals, 77,905
tuberculosis cases, and 888 MDR TB cases notified at the federal level in the
IRHWG countries. India, China, Vietnam, and the Philippines accounted for 41.4%
of the total foreign-born tuberculosis cases and 42.7% of the foreign-born MDR
tuberculosis cases to IRHWG. Interpretation. Collaborative efforts across a small
number of countries have the potential to yield sizeable gains in tuberculosis
control for these large immigrant- and refugee-receiving countries.
PMID- 28424749
TI - Development of Asymmetric Facial Depigmentation in a Patient Treated with
Dasatinib with New-Onset Hypovitaminosis D: Case Report and Review of the
Literature.
AB - Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used to treat
imatinib-resistant chronic myelogenous leukemia (CML), as well as other
Philadelphia chromosome-positive lymphoproliferative disorders. While the most
commonly reported cutaneous side effects with this therapy include a morbilliform
eruption, skin exfoliation, and skin irritation, pigmentary abnormalities have
also been observed, albeit much more rarely. We present the case of a 72-year-old
South Asian male with CML who presented with new-onset hypopigmentation of his
face and scalp three years after a dose increase of dasatinib therapy, in the
setting of newly discovered borderline hypovitaminosis D. Dasatinib and the other
TKIs are believed to induce dyschromias via modulation of the c-kit receptor and
its associated signaling pathway, which is involved in melanocyte survival,
proliferation, and migration.
PMID- 28424750
TI - Celiac Disease Presenting with Immune Thrombocytopenic Purpura.
AB - Celiac disease (CD) is an immunological disorder. Clinical manifestations occur
as a result of intestinal mucosa damage and malabsorption. CD is also associated
with extraintestinal manifestations and autoimmune disorders. The coexistence of
CD and autoimmune diseases has been described before. In this article, a patient
with CD presenting with thrombocytopenia is discussed.
PMID- 28424751
TI - Levodopa Responsive Parkinsonism in Patients with Hemochromatosis: Case
Presentation and Literature Review.
AB - Hemochromatosis is an autosomal recessive disorder which leads to abnormal iron
deposition in the parenchyma of multiple organs causing tissue damage.
Accumulation of iron in the brain has been postulated to be associated with
several neurodegenerative diseases including Parkinson's disease. The excess iron
promotes Parkin and alpha-synuclein aggregation in the neurons. Excess iron has
also been noted in substantia nigra on MRI especially using susceptibility
weighted imaging in patients with Parkinson's disease. We present a case of a
young male with alleles for both C282Y and H63D who presented with signs of
Parkinsonism and demonstrated significant improvement with levodopa treatment.
PMID- 28424752
TI - Cocaine-Like Discriminative Stimulus Effects of Mephedrone and Naphyrone in Mice.
AB - BACKGROUND: In recent years, commercial bath salts products containing synthetic
cathinone analogues have emerged as illicit drugs of abuse. These cathinones are
structurally similar to the psychostimulants 3,4-methylenedioxymethamphetamine
(MDMA) and methamphetamine (METH), and produce their effects via interactions
with monoamine transporters, where smaller compounds (e.g., mephedrone) are
amphetamine-like monoamine releasers, while the structurally larger compounds
(e.g., naphyrone) are cocaine-like monoamine reuptake inhibitors. Individual
cathinones also differ from one another with respect to selectivity among the
three monoamine transporters. STATEMENT OF PURPOSE OF STUDY: This study was
designed to assess the cocaine-like interoceptive effects of synthetic cathinone
analogues functioning as passive monoamine reuptake inhibitors (naphyrone) or as
releasers (mephedrone) in mice in order to compare effectiveness (degree of
substitution) and potency with positive control psychostimulants cocaine, METH,
and MDMA. PROCEDURES: In the present study, mice were trained to discriminate 10
mg/kg cocaine from saline, and substitutions with METH, MDMA, mephedrone,
naphyrone, and morphine were performed. MAIN FINDINGS: Mice reliably
discriminated the cocaine training dose from saline, and METH, MDMA, mephedrone,
and naphyrone all elicited full cocaine-like responding, while morphine did not.
Potency differences were observed such that METH was most potent, while
mephedrone, cocaine, MDMA, and naphyrone exhibited roughly equivalent potency.
PRINCIPAL CONCLUSIONS: These data confirm that interaction with DAT is an
important component of cocaine-like discriminative stimulus effects, and suggest
that synthetic cathinones likely elicit psychostimulant-like abuse-related
effects.
PMID- 28424753
TI - Image-Guided High Intensity Focused Ultrasound System for Large Animal Nerve
Ablation Studies.
AB - High intensity focused ultrasound (HIFU) is a form of thermal ablation technique,
which can treat a variety of medical afflictions. One promising therapeutic use
is the permanent destruction of nerves non-invasively in patients with severe
spasticity or certain types of pain (e.g., phantom limb pain). To this end, HIFU
requires ultrasound guidance, which allows the non-invasive, target-specific
deposition of thermal energy to the targeted nerve, thereby blocking axonal
conduction. In this paper, a composite system comprising both ultrasound-imaging
and HIFU therapy was developed and used to induce localized non-invasive nerve
blockage in an in vivo large animal study. Five pigs were used with the femoral
nerve as the target. Calibrated needle thermocouples inserted at the target site
were employed to monitor the target tissue temperature. The degree of nerve
blockage was assessed by measuring compound action potential (CAP) signal with a
clinical nerve electrophysiology system before and after HIFU exposures. An
average CAP signal amplitude reduction of 49% of baseline with a standard
deviation of 9% was observed after 20-30 min post exposure. These results
demonstrate the feasibility of the proposed ultrasound-guided HIFU modality as a
potential non-invasive nerve ablation method.
PMID- 28424754
TI - Considerations of temperature in the context of the persistence classification in
the EU.
AB - Simulation degradation studies for industrial chemicals, biocidal products and
plant protection products are required in the EU to estimate half-lives in soil,
water and sediment for the comparison to persistence criteria for hazard (P/vP)
assessment, and for use in exposure assessments. There is a discrepancy between
European regulatory approaches regarding the temperature at which degradation
half-lives should be (1) measured in simulation degradation testing of
environmental compartments, and (2) compared to the P/vP criteria. In this paper,
an opinion is provided on the options for the experimental temperature and
extrapolation to other conditions. A review of the historical development of
persistence criteria did not give conclusive evidence of the temperature at which
the half-lives that underpin the P-criteria were measured, but room temperature
is likely. Half-lives measured at 20 degrees C are in line with the intentions
of some international agreements, but in the EU there is a continued political
debate regarding the relevant temperature for comparison with persistence
criteria. Measuring degradation at 20 degrees C has the advantage that
metabolites/transformation products can be identified with greater accuracy, and
that kinetic fits to determine half-lives for parent compounds and metabolites
carry less uncertainty. Extrapolation of half-lives to lower temperatures is
possible for assessing environmental exposure, but the uncertainty of the
persistence classification is smaller when measured half-lives are used for
direct comparison with P/vP criteria, without extrapolation. Model simulations
demonstrate the pattern of concentrations that can be expected for realistic
worst case climate scenarios in the EU based on the half-life of 120 days in soil
at 20 degrees C and of 40 days in water at 20 degrees C, and their temporal and
spatial variability.
PMID- 28424755
TI - Rapid, low cost prototyping of transdermal devices for personal healthcare
monitoring.
AB - The next generation of devices for personal healthcare monitoring will comprise
molecular sensors to monitor analytes of interest in the skin compartment.
Transdermal devices based on microneedles offer an excellent opportunity to
explore the dynamics of molecular markers in the interstitial fluid, however good
acceptability of these next generation devices will require several technical
problems associated with current commercially available wearable sensors to be
overcome. These particularly include reliability, comfort and cost. An essential
pre-requisite for transdermal molecular sensing devices is that they can be
fabricated using scalable technologies which are cost effective. We present here
a minimally invasive microneedle array as a continuous monitoring platform
technology. Method for scalable fabrication of these structures is presented. The
microneedle arrays were characterised mechanically and were shown to penetrate
human skin under moderate thumb pressure. They were then functionalised and
evaluated as glucose, lactate and theophylline biosensors. The results suggest
that this technology can be employed in the measurement of metabolites,
therapeutic drugs and biomarkers and could have an important role to play in the
management of chronic diseases.
PMID- 28424756
TI - Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.
AB - Retroviral vector gene therapy is a promising approach to treating HIV-1.
However, integrated vectors are mutagens with the potential to dysregulate nearby
genes and cause severe adverse side effects. Leukemia has already been a
documented severe adverse event in gene therapy clinical trials for the treatment
of primary immunodeficiencies. These side effects will need to be reduced or
avoided if retroviral vectors are to be used clinically for HIV-1 treatment. The
addition of chromatin insulators to retroviral vectors is a potential strategy
for reducing adverse side effects. Insulators have already been effectively used
in retroviral vectors to reduce genotoxicity in pre-clinical studies. Here, we
will review how insulators function, genotoxicity in gene therapy clinical
trials, the design of insulated retroviral vectors, promising results from
insulated retroviral vector studies, and considerations for the development of
insulated retroviral treatment vectors for HIV-1 gene therapy.
PMID- 28424757
TI - The Emerging Role of Targeted Therapy and Immunotherapy in the Management of
Brain Metastases in Non-Small Cell Lung Cancer.
AB - Lung cancer is the worldwide leading cause of cancer-related mortality in men and
second leading in women. Brain metastases (BM) account for 10% of non-small cell
lung cancer (NSCLC) patients at initial presentation, with another 25-40%
developing BM during the course of their disease. In the last decade, the field
of precision oncology has led to the discovery of a multitude of heterogenous
molecular abnormalities within NSCLC as well as the development of tyrosine
kinase inhibitors that target them. In this review, the focus will be on targeted
therapy and immunotherapy that show efficacy in BM rather than conventional
treatment for multiple BM (such as surgical resection, WBRT, or stereotactic
radiosurgery).
PMID- 28424758
TI - Redox-Related Epigenetic Mechanisms in Glioblastoma: Nuclear Factor (Erythroid
Derived 2)-Like 2, Cobalamin, and Dopamine Receptor Subtype 4.
AB - Glioblastoma is an exceptionally difficult cancer to treat. Cancer is universally
marked by epigenetic changes, which play key roles in sustaining a malignant
phenotype, in addition to disease progression and patient survival. Studies have
shown strong links between the cellular redox state and epigenetics. Nuclear
factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription
factor that upregulates endogenous antioxidant production, and is aberrantly
expressed in many cancers, including glioblastoma. Methylation of DNA and
histones provides a mode of epigenetic regulation, and cobalamin-dependent
reactions link the redox state to methylation. Antagonists of dopamine receptor
subtype 4 (D4 receptor) were recently shown to restrict glioblastoma stem cell
growth by downregulating trophic signaling, resulting in inhibition of functional
autophagy. In addition to stimulating glioblastoma stem cell growth, D4 receptors
have the unique ability to catalyze cobalamin-dependent phospholipid methylation.
Therefore, D4 receptors represent an important node in a molecular reflex pathway
involving Nrf2 and cobalamin, operating in conjunction with redox status and
methyl group donor availability. In this article, we describe the redox-related
effects of Nrf2, cobalamin metabolism, and the D4 receptor on the regulation of
the epigenetic state in glioblastoma.
PMID- 28424759
TI - Antiangiogenesis for Advanced Non-Small-Cell Lung Cancer in the Era of
Immunotherapy and Personalized Medicine.
AB - Over the past decade, patients with advanced non-small-cell lung cancer (NSCLC)
have witnessed substantial advances in regards to therapeutic alternatives. Among
newly developed agents, angiogenesis inhibitors were extensively tested in
different settings and have produced some favorable outcomes despite several
shortcomings. Bevacizumab is the most examined agent in this context and has
demonstrated significant survival benefits when combined with standard
chemotherapy in eligible patients. Preliminary results on the addition of
bevacizumab to erlotinib in patients with EGFR-mutated NSCLC seem promising.
Other antiangiogenic agents were also tested, but ramucirumab and nintedanib are
the only agents with a positive impact on survival. More recently, immune
checkpoint inhibitors (ICIs) have had considerable success due to their prolonged
durations of response, yet response rates are still deemed suboptimal, and
various combination therapies are being tested in an effort to improve efficacy.
Preclinical evidence suggests an immunosuppressive effect of pro-angiogenic
factors, which sets up a plausible rationale for combining ICIs and
antiangiogenic agents. Herein, we review the landmark data supporting the success
of angiogenesis inhibitors, and we discuss the potential for combination with
immunotherapy and targeted agents.
PMID- 28424760
TI - Insights into Local Tumor Microenvironment Immune Factors Associated with
Regression of Cutaneous Melanoma Metastases by Mycobacterium bovis Bacille
Calmette-Guerin.
AB - Mycobacterium bovis bacille Calmette-Guerin (BCG) is listed as an intralesional
(IL) therapeutic option for inoperable stage III in-transit melanoma in the
National Comprehensive Cancer Network Guidelines. Although the mechanism is
unknown, others have reported up to 50% regression of injected lesions, and 17%
regression of uninjected lesions in immunocompetent patients after direct
injection of BCG into metastatic melanoma lesions in the skin. BCG and other
mycobacteria express ligands capable of stimulating the gamma9delta2 T cells.
Therefore, we hypothesized that gamma9delta2 T cells play a role in promoting BCG
mediated antitumor immunity in patients treated with IL-BCG for in-transit
cutaneous melanoma metastases. Indeed, we found gamma9delta2 T cell infiltration
in melanoma skin lesions during the course of IL-BCG treatment. Gene expression
analysis revealed that BCG injection elicits the expression of a vast array of
chemokines in tumor lesions, including strong expression of CXCL9, 10, and 11, a
set of chemokines that attract T cells expressing the CXCR3 chemokine receptor.
In corroboration with our hypothesis, approximately 85% of gammadelta T cells
express high levels of CXCR3 on their surface. Importantly, the injected tumor
lesions also express genes whose protein products are the antigenic ligands for
gammadelta T cells (BTN3A1 and MICB), and the cytokines that are the typical
products of activated gammadelta T cells. Interestingly, we also found that
gammadelta T cells infiltrate the regressed lesions that did not receive BCG
injections. Our study suggests that gamma9delta2 T cells may contribute to
melanoma regression induced by IL-BCG treatment.
PMID- 28424761
TI - Sequencing of blaIMP-Carrying IncN2 Plasmids, and Comparative Genomics of IncN2
Plasmids Harboring Class 1 Integrons.
AB - This work presents the complete nucleotide sequences of p0801-IMP from Klebsiella
pneumoniae, p7121-IMP from K. oxytoca, and p17285-IMP from Citrobacter freundii,
which are recovered from three different cases of nosocomial infection. These
three plasmids represent the first fully sequenced blaIMP-carrying IncN2
plasmids. Further comparative genomics analysis of all the five integron-carrying
IncN2 plasmids p0801-IMP, p7121-IMP, p17285-IMP, pJIE137, and p34983-59.134kb
indicates that they possess conserved IncN2 backbones with limited genetic
variations with respect to gene content and organization. Four class 1 integrons
(blaIMP-1-carrying In1223 in p0801-IMP/p7121-IMP, blaIMP-8-carrying In655 in
p17285-IMP, In27 in pJIE137, and In1130 in p34983-59.134kb), two insertion
sequence-based transposition units (ISEcp1-orfRA1-14 in p17285-IMP, and ISEcp1
blaCTX-M-62-Deltaorf477-orfRA1-14 in pJIE137), and a novel Tn1696-related
transposon Tn6325 carrying In1130 in p34983-59.134kb are indentified in the
plasmid accessory regions. In1223 and In655 represent ancestral Tn402-associated
integrons, while In27 and In1130 belong to complex class 1 integrons. The
relatively small IncN2 backbones are able to integrate different mobile elements
which carry various resistance markers, promoting the accumulation and spread of
antimicrobial resistance genes among enterobacterial species.
PMID- 28424762
TI - Assessment of Sensory Processing Characteristics in Children between 3 and 11
Years Old: A Systematic Review.
AB - The assessment of sensory perception, discrimination, integration, modulation,
praxis, and other motor skills, such as posture, balance, and bilateral motor
coordination, is necessary to identify the sensory and motor factors influencing
the development of personal autonomy. The aim of this work is to study the
assessment tools currently available for identifying different patterns of
sensory processing. There are 15 tests available that have psychometric
properties, primarily for the US population. Nine of them apply to children in
preschool and up to grade 12. The assessment of sensory processing is a process
that includes the use of standardized tests, administration of caregiver
questionnaires, and clinical observations. The review of different studies using
PRISMA criteria or Osteba Critical Appraisal Cards reveals that the most commonly
used tools are the Sensory Integration and Praxis Test, the Sensory Processing
Measure, and the Sensory Profile.
PMID- 28424763
TI - Airway Problems in Neonates-A Review of the Current Investigation and Management
Strategies.
AB - Airway problems in the neonatal population are often life threatening and raise
challenging issues in diagnosis and management. The airway problems can result
from congenital or acquired lesions and can be broadly classified into those
causing obstruction or those due to an abnormal "communication" in the airway.
Many different investigations are now available to identify the diagnosis and
quantify the severity of the problem, and these tests can be simple or invasive.
Bronchography and bronchoscopy are essential to determine the extent and severity
of the airway problem and to plan treatment strategy. Further imaging techniques
help to delineate other commonly associated abnormalities. Echocardiography is
also important to confirm any associated cardiac abnormality. In this review, the
merits and disadvantages of the various investigations now available to the
clinician will be discussed. The current therapeutic strategies are discussed,
and the review will focus on the most challenging conditions that cause the
biggest management conundrums, specifically laryngotracheal cleft, congenital
tracheal stenosis, and tracheobronchomalacia. Management of acquired stenosis
secondary to airway injury from endotracheal intubation will also be discussed as
this is a common problem. Slide tracheoplasty is the preferred surgical option
for long-segment tracheal stenosis, and results have improved significantly.
Stents are occasionally required for residual or recurrent stenosis following
surgical repair. There is sufficient evidence that a multidisciplinary team
approach for managing complex airway issues provides the best results for the
patient. There is ongoing progress in the field with newer diagnostic tools as
well as development of innovative management techniques, such as biodegradable
stents and stem cell-based tracheal transplants, leading to a much better
prognosis for these children in the future.
PMID- 28424766
TI - The Need for Hematology Nurse Education in Low- and Middle-Income Countries: A
Community Case Study in Tanzania.
AB - Hematology-related diseases, such as anemia, malaria, sickle cell disease (SCD),
and blood cancers, have differing rates of survival between high-income and low-
and middle-income countries (LMICs). Nurses in LMICs have an unmet need for
specialty training and education to address hematology and hemato-oncology
disorders. A gap in the literature exists about hematology nurse education and
clinical service demands in LMICs. This community case study documents a
collaborative hematology and basic hemato-oncology education program to
sustainably strengthen nurse capacity at a national referral hospital and
university in Tanzania. The goal of the intervention was to provide culturally
competent nurse training in pediatric and adult hematology. A certified pediatric
nurse practitioner with hematology and oncology experience provided culturally
competent training and staff development to nurses over two weeks to meet this
goal. Prior to development of a training schedule, nurses confidentially
identified five of their top learning needs. Main hematology and basic oncology
educational needs identified by nurses were the management of anemia, safe
handling of cytotoxic agents, and treatment of SCD. The format of the education
varied from bedside teaching to formal presentations to one-on-one individual
discussions. Overall, nurses expressed satisfaction with the education and
verbalized appreciation for teaching and training activities tailored to meet
their needs. Specialized training in hematology and hemato-oncology has the
potential to increase nurses' confidence, respect, and participation in
interprofessional team decision-making. Lessons learned from the impact of
collaborative nurse education and partnership in Tanzania can be generalized to
other LMICs. This community case study highlights the importance of specialty
nurse education, interprofessional development, and global partnerships needed to
improve patient outcomes.
PMID- 28424765
TI - Community Health Volunteers in Primary Healthcare in Rural Uganda: Factors
Influencing Performance.
AB - INTRODUCTION: Community health volunteers (CHVs) play an integral role in primary
healthcare. Several countries rely on CHV programs as a major element in
improving access to care and attaining universal health coverage. However, their
performance has been heterogeneous and at times context-specific, and influenced
by multiple factors. We describe the socio-demographic and workplace
characteristics affecting CHVs' performance in a public health program in rural
western Uganda. METHODS: This was a cross-sectional study based on routine
program data of CHVs serving the catchment of Bwindi Community Hospital, Kanungu
District, South Western Uganda, in 2014 and 2015. Information was collected on
individual socio-demographic and workplace characteristics of the CHVs. To assess
their work output, we defined study-specific targets in terms of attendance at
monthly CHVs' meetings with community health nurses, households followed-up and
reported, children screened for malnutrition, immunization coverage, and health
facility deliveries. Frequencies and proportions are reported for characteristics
and outputs and odds ratios for study-specific factors associated with overall
performance. RESULTS: Of the 508 CHVs, 65% were women, 48% were aged 35 years and
below, and 37% took care of more than the recommended 20-30 households. Seventy
eight percent of the CHVs had >=80% of pregnant women under their care delivering
in health units, 71% had >=95% of the children on schedule for routine
immunization, while 27% screened >=75% of the children under 5 years for
malnutrition. More refresher trainings was associated with better overall
performance [adjusted odds ratio (aOR): 12.2, 95% confidence interval (CI): 1.6
93.6, P = 0.02] while overseeing more than the recommended 20-30 households
reduced overall performance (aOR: 0.6, 95% CI: 0.4-0.9, P = 0.02). CONCLUSION:
Being in-charge of more than the recommended households was associated with
reduced performance of CHVs, while more refresher trainings were associated with
improved performance. If the CHVs are to remain a strategic pillar in universal
health coverage, it is imperative to address those factors known to impact on
their performance.
PMID- 28424764
TI - Diffusion Tensor Imaging Colour Mapping Threshold for Identification of
Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm
Lambs.
AB - PURPOSE: The aim of this study is to examine whether advanced magnetic resonance
imaging (MRI) techniques can detect early brain injury caused by intrauterine
inflammation and inappropriate initial respiratory support in preterm lambs.
HYPOTHESIS: Neuropathology caused by intrauterine inflammation is exacerbated by
mechanical ventilation at birth and is detectable with advanced MRI techniques.
METHODS: Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days
prior to delivery at ~125 days of gestation (85% of gestation), whereupon lambs
were delivered and randomised to receive an injurious (LPS + INJ, n = 6) or
protective (LPS + PROT, n = 6) ventilation strategy. MRI of the brain was
conducted 90 min after preterm delivery, using structural, diffusion tensor
imaging (DTI), and magnetic resonance spectroscopy (MRS) techniques. A colour map
threshold technique was utilised to compare distributions of low diffusivity
voxels in the brains of LPS-exposed lambs with those not exposed to LPS (PROT, n
= 7 PROT and INJ, n = 10). RESULTS: No overt cerebral injury was identified on
structural MRI images of any lamb. However, on DTI, axial diffusivity, radial
diffusivity, and mean diffusivity values were lower and significantly more
heterogeneous in specific brain regions of lambs in the LPS + INJ group compared
to the LPS + PROT group. Colour mapping revealed lower diffusivity in the
thalamus, periventricular white matter, internal capsule, and frontal white
matter in the LPS + INJ group compared to LPS + PROT group. The MRS peak area
ratios of lactate, relative to those for the metabolites creatine, choline, and N
acetylaspartate, were not different between LPS-exposed groups. Lambs exposed to
LPS had lower diffusivity within the white matter regions assessed than non-LPS
treated control lambs. CONCLUSION: DTI colour map threshold techniques detected
early brain injury in preterm lambs exposed to intrauterine inflammation and
detected differences between injurious and protective ventilation strategies. DTI
mapping approaches are potentially useful for early detection of subtle brain
injury in premature infants.
PMID- 28424767
TI - Direct and Indirect Costs of Asthma Management in Greece: An Expert Panel
Approach.
AB - OBJECTIVE: Asthma is a major cause of morbidity and mortality and is associated
with significant economic burden worldwide. The objectives of this study were to
map current resource use associated with the disease management and to estimate
the annual direct and indirect costs per adult patient with asthma. METHODS: A
Delphi panel with seven leading pulmonologists was conducted. A semistructured
questionnaire was developed to elicit data on resource use and treatment
patterns. Unit costs from official, published sources were subsequently assigned
to resource use to estimate direct medical costs. Indirect costs were estimated
as number of work loss days. Cost base year was 2015, and the perspective adopted
was that of the National Organization of Health Care Services Provision, as well
as the societal. RESULTS: Patients with asthma are mainly managed by
pulmonologists (71.4%) and secondarily by general practitioners and internists
(28.6%). The annual cost of managing exacerbations was estimated at ?273.1, while
maintenance costs were estimated at ?1,100.2 per year. Total costs of managing
asthma per patient per year were estimated at ?2,281.8, 64.4% of which
represented direct medical costs. Of the direct costs, pharmaceutical treatment
was the key driver, accounting for 63.9 and 41.2% of direct and total costs,
respectively. Direct non-medical costs (patient travel and waiting time) were
estimated at ?152.3. Indirect costs accounted for 28.9% of total costs.
CONCLUSION: Asthma is a chronic condition, the management of which constrains the
already limited Greek health care resources. The increasing prevalence of the
disease raises concerns as it could translate per patient costs into a
significant burden for the Greek health care system. Thus, the prevention, self
management, and improved quality of care for asthma should find a place in the
health policy agenda in Greece.
PMID- 28424768
TI - Model-Based Policymaking: A Framework to Promote Ethical "Good Practice" in
Mathematical Modeling for Public Health Policymaking.
AB - Mathematical models are increasingly relied upon as decision support tools, which
estimate risks and generate recommendations to underpin public health policies.
However, there are no formal agreements about what constitutes professional
competencies or duties in mathematical modeling for public health. In this
article, we propose a framework to evaluate whether mathematical models that
assess human and animal disease risks and control strategies meet standards
consistent with ethical "good practice" and are thus "fit for purpose" as
evidence in support of policy. This framework is derived from principles of
biomedical ethics: independence, transparency (autonomy), beneficence/non
maleficence, and justice. We identify ethical risks associated with model
development and implementation and consider the extent to which scientists are
accountable for the translation and communication of model results to
policymakers so that the strengths and weaknesses of the scientific evidence base
and any socioeconomic and ethical impacts of biased or uncertain predictions are
clearly understood. We propose principles to operationalize a framework for
ethically sound model development and risk communication between scientists and
policymakers. These include the creation of science-policy partnerships to
mutually define policy questions and communicate results; development of
harmonized international standards for model development; and data stewardship
and improvement of the traceability and transparency of models via a searchable
archive of policy-relevant models. Finally, we suggest that bespoke ethical
advisory groups, with relevant expertise and access to these resources, would be
beneficial as a bridge between science and policy, advising modelers of potential
ethical risks and providing overview of the translation of modeling advice into
policy.
PMID- 28424770
TI - Recent Advances in Bioink Design for 3D Bioprinting of Tissues and Organs.
AB - There is a growing demand for alternative fabrication approaches to develop
tissues and organs as conventional techniques are not capable of fabricating
constructs with required structural, mechanical, and biological complexity. 3D
bioprinting offers great potential to fabricate highly complex constructs with
precise control of structure, mechanics, and biological matter [i.e., cells and
extracellular matrix (ECM) components]. 3D bioprinting is an additive
manufacturing approach that utilizes a "bioink" to fabricate devices and
scaffolds in a layer-by-layer manner. 3D bioprinting allows printing of a cell
suspension into a tissue construct with or without a scaffold support. The most
common bioinks are cell-laden hydrogels, decellulerized ECM-based solutions, and
cell suspensions. In this mini review, a brief description and comparison of the
bioprinting methods, including extrusion-based, droplet-based, and laser-based
bioprinting, with particular focus on bioink design requirements are presented.
We also present the current state of the art in bioink design including the
challenges and future directions.
PMID- 28424769
TI - Folates in Plants: Research Advances and Progress in Crop Biofortification.
AB - Folates, also known as B9 vitamins, serve as donors and acceptors in one-carbon
(C1) transfer reactions. The latter are involved in synthesis of many important
biomolecules, such as amino acids, nucleic acids and vitamin B5. Folates also
play a central role in the methyl cycle that provides one-carbon groups for
methylation reactions. The important functions fulfilled by folates make them
essential in all living organisms. Plants, being able to synthesize folates de
novo, serve as an excellent dietary source of folates for animals that lack the
respective biosynthetic pathway. Unfortunately, the most important staple crops
such as rice, potato and maize are rather poor sources of folates. Insufficient
folate consumption is known to cause severe developmental disorders in humans.
Two approaches are employed to fight folate deficiency: pharmacological
supplementation in the form of folate pills and biofortification of staple crops.
As the former approach is considered rather costly for the major part of the
world population, biofortification of staple crops is viewed as a decent
alternative in the struggle against folate deficiency. Therefore, strategies,
challenges and recent progress of folate enhancement in plants will be addressed
in this review. Apart from the ever-growing need for the enhancement of
nutritional quality of crops, the world population faces climate change
catastrophes or environmental stresses, such as elevated temperatures, drought,
salinity that severely affect growth and productivity of crops. Due to immense
diversity of their biochemical functions, folates take part in virtually every
aspect of plant physiology. Any disturbance to the plant folate metabolism leads
to severe growth inhibition and, as a consequence, to a lower productivity.
Whereas today's knowledge of folate biochemistry can be considered very profound,
evidence on the physiological roles of folates in plants only starts to emerge.
In the current review we will discuss the implication of folates in various
aspects of plant physiology and development.
PMID- 28424772
TI - Putting Cells into Context.
PMID- 28424771
TI - PTK7 Faces the Wnt in Development and Disease.
AB - PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane
receptor regulating various processes in embryonic development and tissue
homeostasis. On a cellular level PTK7 affects the establishment of cell polarity,
the regulation of cell movement and migration as well as cell invasion. The PTK7
receptor has been shown to interact with ligands, co-receptors, and intracellular
transducers of Wnt signaling pathways, pointing to a function in the fine-tuning
of the Wnt signaling network. Here we will review recent findings implicating
PTK7 at the crossroads of Wnt signaling pathways in development and disease.
PMID- 28424773
TI - Septins Focus Cellular Growth for Host Infection by Pathogenic Fungi.
AB - One of the key challenges faced by microbial pathogens is invasion of host
tissue. Fungal pathogens adopt a number of distinct strategies to overcome host
cell defenses, including the development of specialized infection structures, the
secretion of proteins that manipulate host responses or cellular organization,
and the ability to facilitate their own uptake by phagocytic mechanisms. Key to
many of these adaptations is the considerable morphogenetic plasticity displayed
by pathogenic species. Fungal pathogens can, for example, shift their growth
habit between non-polarized spores, or yeast-like cells, and highly polarized
hyphal filaments. These polarized filaments can then elaborate differentiated
cells, specialized to breach host barriers. Septins play fundamental roles in the
ability of diverse fungi to undergo shape changes and organize the F-actin
cytoskeleton to facilitate invasive growth. As a consequence, septins are
increasingly implicated in fungal pathogenesis, with many septin mutants
displaying impairment in their ability to cause diseases of both plants and
animals. In this mini-review, we show that a common feature of septin mutants is
the emergence of extra polar outgrowths during morphological transitions, such as
emergence of germ tubes from conidia or branches from hyphae. We propose that
because septins detect and stabilize membrane curvature, they prevent extra polar
outgrowths and thereby focus fungal invasive force, allowing substrate invasion.
PMID- 28424774
TI - Cardiac Radionuclide Imaging in Rodents: A Review of Methods, Results, and
Factors at Play.
AB - The interest around small-animal cardiac radionuclide imaging is growing as
rodent models can be manipulated to allow the simulation of human diseases. In
addition to new radiopharmaceuticals testing, often researchers apply well
established probes to animal models, to follow the evolution of the target
disease. This reverse translation of standard radiopharmaceuticals to rodent
models is complicated by technical shortcomings and by obvious differences
between human and rodent cardiac physiology. In addition, radionuclide studies
involving small animals are affected by several extrinsic variables, such as the
choice of anesthetic. In this paper, we review the major cardiac features that
can be studied with classical single-photon and positron-emitting
radiopharmaceuticals, namely, cardiac function, perfusion and metabolism, as well
as the results and pitfalls of small-animal radionuclide imaging techniques. In
addition, we provide a concise guide to the understanding of the most frequently
used anesthetics such as ketamine/xylazine, isoflurane, and pentobarbital. We
address in particular their mechanisms of action and the potential effects on
radionuclide imaging. Indeed, cardiac function, perfusion, and metabolism can all
be significantly affected by varying anesthetics and animal handling conditions.
PMID- 28424775
TI - Second-line Treatment of Non-Small Cell Lung Cancer: Focus on the Clinical
Development of Dacomitinib.
AB - Dacomitinib is a second-generation, irreversible, covalent pan-HER tyrosine
kinase inhibitor (TKI). It showed potent EGFR signaling inhibition in
experimental models, including first-generation TKI-resistant non-small cell lung
cancer (NSCLC) cell lines. This preclinical efficacy did not translate into
clinically meaningful treatment benefits for advanced, pretreated, molecularly
unselected NSCLC patients enrolled in two parallel phase III trials. Dacomitinib
and erlotinib showed overlapping efficacy data in chemotherapy-pretreated EGFR
wild-type (WT) patients in the ARCHER 1009 trial. Similarly, it failed to
demonstrate any survival benefits as compared to placebo in EGFR WT subsets
progressing on chemotherapy and at least one previous first-generation TKI
(erlotinib or gefitinib) in the BR.26 trial. In the case of EGFR-mutant NSCLCs, a
pooled analysis of the ARCHER 1009 and ARCHER 1028 trials comparing the efficacy
of dacomitinib vs. erlotinib in chemotherapy-pretreated, EGFR TKI-naive patients
showed a trend to a longer progression-free survival (PFS) and overall survival
in favor of dacomitinib that did not reach statistical significance, with a
higher rate of treatment related adverse events (mainly skin rash, paronychia,
and gastrointestinal toxicities). On the other hand, the clinical activity in
patients with EGFR-mutant NSCLCs with acquired TKI resistance that were included
in phase II/III trials was equally poor (response rate <10%; PFS 3-4 months).
Therefore, with the results of the ARCHER 1050 trial (NCT01774721) still pending,
the current clinical development of dacomitinib is largely focused on EGFR
mutant, TKI-naive patients. Here, we review the most relevant clinical data of
dacomitinib in advanced NSCLC. We discuss the potential role of dacomitinib in
pretreated EGFR WT and EGFR-mutant (TKI-naive and TKI-resistant) patients.
Finally, we briefly comment the available clinical data of dacomitinib in HER2
mutant NSCLC patients.
PMID- 28424776
TI - Socially Responsible Surgery: Building Recognition and Coalition.
AB - IMPORTANCE: Socially responsible surgery (SRS) integrates surgery and public
health, providing a framework for research, advocacy, education, and clinical
practice to address the social barriers of health that decrease surgical access
and worsen surgical outcomes in underserved patient populations. These patients
face disparities in both health and in health care, which can be effectively
addressed by surgeons in collaboration with allied health professionals.
OBJECTIVE: We reviewed the current state of surgical access and outcomes of
underserved populations in American rural communities, American urban
communities, and in low- and middle-income countries. EVIDENCE REVIEW: We
searched PubMed using standardized search terms and reviewed the reference lists
of highly relevant articles. We reviewed the reports of two recent global surgery
commissions. CONCLUSION: There is an opportunity for scholarship in rural
surgery, urban surgery, and global surgery to be unified under the concept of
SRS. The burden of surgical disease and the challenges to management demonstrate
that achieving optimal health outcomes requires more than excellent perioperative
care. Surgeons can and should regularly address the social determinants of health
experienced by their patients. Formalized research and training opportunities are
needed to meet the growing enthusiasm among surgeons and trainees to develop
their practice as socially responsible surgeons.
PMID- 28424777
TI - Influence of Cellular Composition and Exogenous Activation on Growth Factor and
Cytokine Concentrations in Canine Platelet-Rich Plasmas.
AB - OBJECTIVE: The purposes of this study were to (1) evaluate correlations among
platelet, leukocyte, growth factor, and cytokine concentrations in canine
platelet-rich plasmas (PRPs) produced from five different canine PRP
concentrating systems and (2) compare the effects of different activation
protocols on platelet activation and growth factor release from one of these
PRPs. METHODS: PRP was made using blood from 15 dogs and each of 5 different PRP
systems in a cross-over design. Complete blood counts were performed to quantify
platelet and leukocyte concentrations. PRPs were activated, or not, according to
manufacturer instructions, and transforming growth factor-beta1 (TGF-beta1),
platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor,
and tumor necrosis factor-alpha (TNF-alpha) were quantified. Differences among
platelet, leukocyte, and growth factor concentration were compared among the
different systems. Correlations between platelet and anabolic growth factor
concentrations were assessed. Subsequently, PRP was made from 12 additional dogs
using one of the devices. Each PRP was divided into three aliquots that were
activated with calcium chloride (CaCl2), human gamma-thrombin (HGT), or not
activated. Expression of CD62P and platelet-bound fibrinogen (CAP1) was
quantified for each activation group. Concentrations of TGF-beta1, PDGF-BB, and
TNF-alpha were also quantified for each activation group and a fourth group that
was frozen/thawed. Differences among activation groups were assessed by a
Friedman test. RESULTS: There were statistically significant differences among
the PRPs made with difference devices with regard to platelet, leukocyte, TGF
beta1, and PDGF-BB concentrations (p < 0.0001). There were weak to moderate
correlations (R2 = 0.07-0.58) between platelet and anabolic growth factor
concentrations but it appeared that activation had a greater effect on growth
factor concentration than did cellular composition. Intentional platelet
activation significantly increased CD62P and CAP1 expression as well as TGF-beta1
and PDGF-BB concentrations in the one PRP in which all activation methods were
assessed. Activation with HGT resulted in the greatest platelet activation, and
CaCl2 and freeze/thaw elicited moderate increases in either growth factor release
or CD62P and CAP1 expression. CONCLUSION: There are positive correlations between
platelet and anabolic growth factor concentrations in canine PRPs. However,
intentional platelet activation has a greater effect on growth factor delivery
than platelet concentration. Thrombin provides more robust activation than CaCl2.
PMID- 28424778
TI - Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and
Respiratory Syndrome across Different Regions and Production Systems of the US.
AB - Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most
impactful disease for the North American swine industry, due to its known
considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors
and reports weekly new PRRS cases in 766 sow herds across the US. The time
dependent reproduction number (TD-R) is a measure of a pathogen's
transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at
the regional and system levels. The primary objective of the study here was to
estimate the TD-R values for PRRSV using regional and system-level PRRS data, and
to contrast it with commonly used metrics of disease, such as incidence estimates
and space-time clusters. The second objective was to test whether the estimated
TD-Rs were homogenous across four US regions. Retrospective monthly incidence
data (2009-2016) were available from the SHMP. The dataset was divided into four
regions based on location of participants, and demographic and environmental
features, namely, South East (North Carolina), Upper Midwest East (UME,
Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma
panhandle). Generation time distributions were fit to incidence data for each
region, and used to calculate the TD-Rs. The Kruskal-Wallis test was used to
determine whether the median TD-Rs differed across the four areas. Furthermore,
we used a space-time permutation model to assess spatial-temporal patterns for
the four regions. Results showed TD-Rs were right skewed with median values close
to "1" across all regions, confirming that PRRS has an overall endemic nature.
Variation in the TD-R patterns was noted across regions and production systems.
Statistically significant periods of PRRSV spread (TD-R > 1) were identified for
all regions except UME. A minimum of three space-time clusters were detected for
all regions considering the time period examined herein; and their overlap with
"spreader events" identified by the TD-R method varied according to region. TD-Rs
may help to measure PRRS spread to understand, in quantitative terms, disease
spread, and, ultimately, support the design, implementation, and monitoring of
interventions aimed at mitigating the impact of PRRSV spread in the US.
PMID- 28424779
TI - The Effectiveness of Various Salacca Vinegars as Therapeutic Agent for Management
of Hyperglycemia and Dyslipidemia on Diabetic Rats.
AB - The aim of this study was to explore the potency of salacca vinegar made from
various Indonesian salacca fruit extracts as therapeutic agent for hyperglycemia
and dyslipidemia for STZ-induced diabetic rats. The rats were grouped into
untreated rats, STZ-induced diabetic rats without treatment, and STZ-induced
diabetic rats treated with Pondoh salacca vinegar, Swaru salacca vinegar, Gula
Pasir salacca vinegar, Madu salacca vinegar, or Madura salacca vinegar. Parameter
observed included blood glucose, total cholesterol (TC), high density lipoprotein
(HDL), low density lipoprotein (LDL), triglyceride (TG), malondialdehyde (MDA),
superoxide dismutase (SOD), and pancreas histopathology of the samples. The
results demonstrated that all salacca vinegars were capable of reducing blood
sugar (from 25.1 to 62%) and reducing LDL (from 9.5 to 14.8 mg/dL), TG (from 58.3
to 69.5 mg/dL), MDA (from 1.1 to 2.2 mg/dL), and TC (from 56.3 to 70.5 mg/dL) as
well as increasing HDL blood sugar of STZ-induced diabetic Wistar rats (from 52.3
to 60 mg/dL). Various salacca vinegars were also capable of regenerating
pancreatic cells. Nevertheless, the ability of Swaru salacca vinegar to manage
hyperglycemia and dyslipidemia appeared to be superior to other salacca vinegars.
Swaru salacca vinegar is a potential therapeutic agent to manage hyperglycemia
and dyslipidemia of STZ-induced diabetic rats.
PMID- 28424780
TI - Corrigendum to "Influence of a 10-Day Mimic of Our Ancient Lifestyle on
Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of
Origin"".
AB - [This corrects the article DOI: 10.1155/2016/6935123.].
PMID- 28424781
TI - Postembedding Decalcification of Mineralized Tissue Sections Preserves the
Integrity of Implanted Biomaterials and Minimizes Number of Experimental Animals.
AB - Bone histology of decalcified or undecalcified samples depends on the
investigation. However, in research each method provides different information to
answer the scientific question. Decalcification is the first step after sample
fixation and governs what analysis is later feasible on the sections. Besides,
decalcification is favored for immunostaining and in situ hybridization.
Otherwise, sample decalcification can be damaging to bone biomaterials implants
that contains calcium or strontium. On the other hand, after decalcification
mineralization cannot be assessed using histology or imaging mass spectrometry.
The current study provides a solution to the hardship caused by material presence
within the bone tissue. The protocol presents a possibility of gaining sequential
and alternating decalcified and undecalcified sections from the same bone sample.
In this manner, investigations using histology, protein signaling, in situ
hybridization, and mass spectrometry on the same sample can better answer the
intended research question. Indeed, decalcification of sections and grindings
resulted in well-preserved sample and biomaterials integrity. Immunostaining was
comparable to that of classically decalcified samples. The study offers a novel
approach that incites correlative analysis on the same sample and reduces the
number of processed samples whether clinical biopsies or experimental animals.
PMID- 28424782
TI - Clinical Significance of Preoperative Albumin and Globulin Ratio in Patients with
Gastric Cancer Undergoing Treatment.
AB - Background. The pretreatment albumin and globulin ratio (AGR) was an inflammation
associated factor which was related to the overall survival in various
malignancies. The aim of this study was to evaluate the prognostic value of AGR
in patients with gastric cancer. Method. This retrospective study included 862
cases pathologically diagnosed with gastric cancer. All patients were randomly
divided into the testing group (431 cases) and validation group (431 cases). The
relationships of AGR with clinicopathologic characteristics and prognosis were
analyzed by Kaplan-Meier and Cox regression methods. Results. In the testing
group, the median overall survival was 26.90 months and the cutoff value of AGR
was 1.50 based on R language. Kaplan-Meier analysis showed that lower AGR was
correlated with poorer overall survival. Multivariate analysis demonstrated that
AGR was an independent prognostic factor for overall survival (HR: 0.584, 95% CI
= 0.351-0.973, and p = 0.039). In the validation group, the median overall
survival was 24.10 months. Lower AGR (<=1.50) also had a significantly poorer
overall survival by Kaplan-Meier analysis. According to multivariate analysis,
the AGR was also confirmed to be an independent prognostic factor for overall
survival (HR: 0.578, 95% CI = 0.373-0.897, and p = 0.015). Conclusions. Our study
suggested that the pretreatment AGR could be a prognostic biomarker for overall
survival in patients with gastric cancer.
PMID- 28424783
TI - Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP
alpha and PPAR-gamma Expression in 3T3-L1 Adipocytes.
AB - Many studies have comprehensively examined the venom of Ophiophagus hannah snake.
Its venom comprises different compounds exhibiting a wide range of
pharmacological activities. In this investigation, four peptide fractions (PFs),
ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O.
hannah were separated by HPLC and investigated for their inhibitory activity on
adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further
purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two
peptides on 3T3-L1 adipocytes, it was revealed that, at 10 MUg/mL, pOh2 was able
to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without
affecting cell viability. Furthermore, the pOh2 downregulated the gene expression
of important transcription factors C/EBP-alpha and PPAR-gamma. In addition, aP2
and GPDH adipocyte-specific markers were also significantly reduced compared to
untreated differentiated cells. Taken together, pOh2 inhibited the expression of
key transcription factors C/EBP-alpha and PPAR-gamma and their target genes, aP2
and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this
novel class of peptide might have potential for in vivo antiobesity effects.
PMID- 28424784
TI - Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected
to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation.
AB - Connexin 43 (Cx43) is the major component protein in astrocytic gap junction
communication. Recent studies have shown the cellular processes of gap junction
internalization and degradation, but many details remain unknown. This study
investigated the distribution of Cx43 and its mechanism after ischemic insult.
Astrocyte culture system and a model of ischemia/reperfusion (IR) or oxygen
glucose deprivation and reoxygenation (OGDR) were established. Cx43 distribution
was observed by laser scanning confocal microscopy under different cultivation
conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and
MAPRE1 (microtubule-associated protein RP/EB family member 1) expression at
different time points. The total number of Cx43 was unchanged in the normal and
IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were
significantly greater than that of the normal group. Particles in the cytoplasm
were significantly fewer after endocytosis was blocked by dynasore. There was no
difference among the groups at each time point regarding protein or gene
expression of MAPRE1. We concluded that internalization of Cx43 into the
cytoplasm occurred during ischemia, which was partially mediated through
endocytosis, not by the change of Cx43 quantity. Moreover, internalization was
not related to microtubule transport.
PMID- 28424785
TI - The Impact of Homocysteine, Vitamin B12, and Vitamin D Levels on Functional
Outcome after First-Ever Ischaemic Stroke.
AB - We explored the relationship between acute ischaemic stroke (IS) early functional
outcome and serum levels of homocysteine, vitamin B12, and D in a
noninterventional prospective clinical study. We enrolled 50 patients with first
ever IS and performed laboratory tests and functional assessment at three time
points: on admission and three and six months after stroke. Modified Rankin Scale
(mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all
participants by trained examiner blinded to laboratory data. Patients did not
receive treatment that might alter laboratory data. Admission NIHSS correlated
with homocysteine levels (r = 0.304, p < 0.05), B12 level (r = -0.410, p < 0.01),
and vitamin D levels (r = -0.465, p < 0.01). Functional outcome measures (BI and
mRS) did not significantly correlate with homocysteine and vitamin D3 levels at 3
and 6 months. However, a positive correlation with vitamin B12 levels was
detected for BI both at 3 and 6 months and mRS at 6 months. Higher serum vitamin
B12 levels were associated with better functional outcome at follow-up.
PMID- 28424786
TI - Immunocytochemistry Improving the Diagnosis of Trichomonas vaginalis Infections.
AB - The aim of this study was to evaluate the immunocytochemistry (ICC) to diagnose
trichomoniasis, particularly asymptomatic infections. By culture serial
dilutions, ICC was able to detect 1 trophozoite/mL, while the culture was
positive up to 100 trophozoites/mL. The ICC in vivo detection capability was
assessed in vaginal secretions of mice experimentally infected and in vaginal
swabs from asymptomatic HIV-positive pregnant women compared with culture. All
vaginal secretion samples from mice were positive according to both methods.
Swabs from fifty-five asymptomatic women were positive in four (7.27%) of them by
culture. Beyond these four, another ten (25.45%) women were positive by
immunocytochemistry, proving their higher sensitivity (p = 0.002), noticing 3.5
times more positives. ICC had better performance in both successive dilutions as
in asymptomatic women, showing higher sensitivity and specificity. In this way,
its facility of execution and cost-effectiveness support its practicality, as a
routine procedure to diagnose trichomoniasis not only when the parasite load is
lower but probably in all clinical scenarios.
PMID- 28424787
TI - Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System
Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei
Jianpi Formula in Treating COPD.
AB - In previous work, we identified 145 active compounds from Bufei Jianpi formula
(BJF) by system pharmacology and found that BJF showed short-term effect on
chronic obstructive pulmonary disease (COPD) rats. Here, we applied the
transcriptomic, proteomic, and metabolomics approaches to illustrate the long
term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD
effect through decreasing inflammatory cytokines level, preventing protease
antiprotease imbalance and collagen deposition on week 32 by continuous oral
administration to rats from weeks 9 to 20. Subsequently, applying the
transcriptomic, proteomic, and metabolomics techniques, we detected a number of
regulated genes, proteins, and metabolites, mainly related to antioxidant
activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF
treated rats. Afterwards, we integrated system pharmacology target, transcript,
protein, and metabolite data sets and found that many genes, proteins, and
metabolites in rats BJF-treated group and the target proteins of BJF were mainly
attributed to lipid metabolism, inflammatory response, oxidative stress, and
focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably
by system regulation of the lipid metabolism, inflammatory response pathways
oxidative stress, and focal adhesion.
PMID- 28424788
TI - Fully Automated Robust System to Detect Retinal Edema, Central Serous
Chorioretinopathy, and Age Related Macular Degeneration from Optical Coherence
Tomography Images.
AB - Maculopathy is the excessive damage to macula that leads to blindness. It mostly
occurs due to retinal edema (RE), central serous chorioretinopathy (CSCR), or age
related macular degeneration (ARMD). Optical coherence tomography (OCT) imaging
is the latest eye testing technique that can detect these syndromes in early
stages. Many researchers have used OCT images to detect retinal abnormalities.
However, to the best of our knowledge, no research that presents a fully
automated system to detect all of these macular syndromes is reported. This paper
presents the world's first ever decision support system to automatically detect
RE, CSCR, and ARMD retinal pathologies and healthy retina from OCT images. The
automated disease diagnosis in our proposed system is based on multilayered
support vector machines (SVM) classifier trained on 40 labeled OCT scans (10
healthy, 10 RE, 10 CSCR, and 10 ARMD). After training, SVM forms an accurate
decision about the type of retinal pathology using 9 extracted features. We have
tested our proposed system on 2819 OCT scans (1437 healthy, 640 RE, and 742 CSCR)
of 502 patients from two different datasets and our proposed system correctly
diagnosed 2817/2819 subjects with the accuracy, sensitivity, and specificity
ratings of 99.92%, 100%, and 99.86%, respectively.
PMID- 28424789
TI - Cognitive-Behavioral Coping, Illness Perception, and Family Adaptability in
Oncological Patients with a Family History of Cancer.
AB - Aim. The study investigated the differences between patients with and without a
family history of cancer regarding coping strategies, illness perception, and
family adaptability to the disease. Material and Methods. A total of 124 patients
diagnosed with cancer were included in the research (55 of them with a family
history of cancer). The Cognitive Emotion Regulation Questionnaire, the Strategic
Approach to Coping Scale, the Family Adaptability and Cohesion Scale, and the
Illness Perception Questionnaire were applied. The data were processed using the
SPSS 21 software. Results. Patients with previous records of cancer in the family
get significantly higher scores for the illness coherence factor. Family
satisfaction is significantly higher for patients with a genetic risk, compared
to the one reported by patients who suffer from the disease but have no genetic
risk. Cognitive-behavioral coping strategies and family cohesion are factors that
correlate with an adaptive perception of the illness in the case of patients with
a family history of cancer. Conclusion. Results are important for the
construction of strategies used for patients with a family history of cancer.
PMID- 28424790
TI - Development of Isothermal Recombinase Polymerase Amplification Assay for Rapid
Detection of Porcine Circovirus Type 2.
AB - Porcine circovirus virus type II (PCV2) is the etiology of postweaning
multisystemic wasting syndrome (PMWS), porcine dermatitis, nephropathy syndrome
(PDNS), and necrotizing pneumonia. Rapid diagnosis tool for detection of PCV2
plays an important role in the disease control and eradication program.
Recombinase polymerase amplification (RPA) assays using a real-time fluorescent
detection (PCV2 real-time RPA assay) and RPA combined with lateral flow dipstick
(PCV2 RPA LFD assay) were developed targeting the PCV2 ORF2 gene. The results
showed that the sensitivity of the PCV2 real-time RPA assay was 102 copies per
reaction within 20 min at 37 degrees C and the PCV2 RPA LFD assay had a detection
limit of 102 copies per reaction in less than 20 min at 37 degrees C. Both assays
were highly specific for PCV2, with no cross-reactions with porcine circovirus
virus type 1, foot-and-mouth disease virus, pseudorabies virus, porcine
parvovirus, porcine reproductive and respiratory syndrome virus, and classical
swine fever virus. Therefore, the RPA assays provide a novel alternative for
simple, sensitive, and specific identification of PCV2.
PMID- 28424791
TI - Antifatigue Effects of Antrodia cinnamomea Cultured Mycelium via Modulation of
Oxidative Stress Signaling in a Mouse Model.
AB - Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects.
In this study, we aim to assess whether the antifatigue effects of A. cinnamomea
mycelia (AC) and its underlying mechanisms are related to oxidative stress
signaling using behavioral mouse models and biochemical indices detection. Mice
were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks.
AC had no effect on the spontaneous activities of mice indicating its safety on
central nervous system. Furthermore, results obtained from weight-loaded forced
swimming test, rotary rod test, and exhausted running test confirmed that AC
significantly enhanced exercise tolerance of mice. Biochemical indices levels
showed that these effects were closely correlated with inhibiting the depletion
of glycogen and adenosine triphosphate stores, regulating oxidative stress
related parameters (superoxide dismutase, glutathione peroxidase, reactive oxygen
species, and malondialdehyde) in serum, skeletal muscle, and liver of mice.
Moreover, the effects of AC may be related with its regulation on the activations
of AMP-activated protein kinase, protein kinase B, and mammalian target of
rapamycin in liver and skeletal muscle of mice. Altogether, our data suggest that
the antifatigue properties of AC may be one such modulation mechanism via
oxidative stress-related signaling in mice.
PMID- 28424793
TI - A Model-Based Meta-Analysis Evaluating Gender Differences on Blood Flow Responses
to Brachial Artery Infusions of Acetylcholine, Albuterol, ATP, Bradykinin,
Estradiol, Glyceryl Trinitrate, L-NMMA, Nevibolol, Norepinephrine, Sodium
Nitroprusside, Substance P, and Verapamil.
AB - INTRODUCTION: Numerous studies have emerged over the course of several decades
describing the properties of drugs eliciting vasodilatory or vasoconstrictor
responses in the human vasculature. During drug development, decisions to move
forward with testing with a new chemical entity are very costly. To fund or not
to fund development, go or no-go, decisions are often limited by efficacy
comparisons with the current products on the market. The primary aim of this
paper is to use dose-response modeling and simulations to quantify differences in
blood flow to Acetylcholine, Albuterol, ATP, Bradykinin, 17beta-Estradiol,
Glyceryl Trinitrate, L-NMMA, Nevibolol, Norepinephrine, Sodium Nitroprusside,
Substance P, and Verapamil. METHODS: Five studies were identified in the
literature that included a total of 12 compounds. Infusion doses were normalized
to nmol/min and forearm blood flow values were normalized and scaled to the
percent increase or decrease in forearm blood flow from baseline resting values.
The original published studies were mathematically modeled using the Emax model
or Sigmoid Emax model equation parameters. Lastly, dose-response simulations of
higher doses using a virtual population were produced to account for population
variability. RESULTS: The gender difference between the Emax estimates,
interpreted as the %Change from Baseline resting forearm blood flow, were found
to be: Albuterol 253%, Acetylcholine 231%, Substance P 159%, Verapamil 145%,
Bradykinin 42%, Sodium Nitroprusside 41%, and Glyceryl Trinitrate 26%.
Contrastingly, Norepinephrine and L-NMMA Emax gender difference resulted in a 6%
and 7% difference, respectively. CONCLUSION: These results provide insight into
the differences in men and women seen in anti-hypertensive patient management.
Further, the modeling estimates provide pharmacometricians evaluating new
compounds with mathematical parameters for comparative efficacy studies through
the various phases of drug development.
PMID- 28424792
TI - Sustained High Levels of Both Total and High Molecular Weight Adiponectin in
Plasma during the Convalescent Phase of Haemorrhagic Fever with Renal Syndrome
Are Associated with Disease Severity.
AB - Haemorrhagic fever with renal syndrome (HFRS) is characterised by an uncontrolled
immune response that causes vascular leakage. Adiponectin (APN) is an
adipocytokine involved in prorevascularisation and immunomodulation. To
investigate the possible effects of APN in the pathogenesis of HFRS, total and
high molecular weight (HMW) APN levels in the plasma of patients with HFRS were
quantified using enzyme-linked immunosorbent assay (ELISA). Compared with those
in healthy controls, the plasma total and HMW APN levels in patients were
elevated to different degrees from the fever onset and remained high at the
convalescent phase. Consistent with these results, western blot analysis
additionally showed that low molecular weight (LMW), middle molecular weight
(MMW), and HMW APN levels were all elevated and contributed to the elevation of
the total APN level. Importantly, sustained high levels of total and HMW APN at
the convalescent phase were significantly higher in patients with critical
disease than those in patients with mild or moderate disease. Moreover, total and
HMW APN levels negatively correlated with white blood cell count and positively
correlated with platelet count and serum albumin level. These results may provide
insights into understanding the roles of total and HMW APN in the pathogenesis of
HFRS.
PMID- 28424794
TI - Study design and baseline results of an open-label cluster randomized community
intervention trial to assess the effectiveness of a modified mass deworming
program in reducing hookworm infection in a tribal population in southern India.
AB - INTRODUCTION: Hookworm infection is a leading cause of iron deficiency anemia and
malnutrition in resource-poor settings. Periodic mass deworming with
anthelminthic drugs remains the cornerstone of hookworm control efforts
worldwide. Reinfection following treatment occurs, reflecting the human host's
inability to acquire immunity following exposure to an untreated reservoir of
infection. This cluster randomized trial will evaluate the effectiveness of a
modified, population-based, mass deworming strategy in reducing hookworm
infection in an endemic southern Indian population. METHODS: Forty five tribal
villages were randomized into three groups: one received annual treatment; the
second received two rounds of treatment at 1-month intervals; and the third
received four rounds of treatment - two rounds 1 month apart at the beginning,
followed by another two after 6 months. Stool samples collected through cross
sectional parasitological surveys pre- and post-intervention, and at 3-monthly
intervals for a period of 1 year were tested for presence of hookworm ova. Long
term effectiveness of treatment will be assessed through another survey conducted
2 years after the last treatment cycle. RESULTS: From a population of 11,857
individuals, 8681 (73.2%) were found to be eligible and consented to participate,
out-migration being the primary reason for non-participation. Baseline stool
samples were obtained from 2082 participants, with 18.5% having hookworm
infection, although majority were low intensity infections (<2000 eggs per gram
of feces). DISCUSSION: This study will help identify the optimal mass deworming
strategy that can achieve the greatest impact in the shortest period of time,
particularly in settings where long-term program sustainability is a challenge.
PMID- 28424795
TI - An open-label cluster randomised trial to evaluate the effectiveness of a
counselling intervention on linkage to care among HIV-infected patients in
Uganda: Study design.
AB - INTRODUCTION: Home-based HIV counselling & testing (HBHCT) is highly acceptable
and has the potential to increase HIV testing uptake in sub-Saharan Africa.
However, data are lacking on strategies that can effectively link HIV-positive
individuals identified through HBHCT to care. This trial was designed to assess
the effectiveness of two brief home-based counselling sessions on linkage to
care, provided subsequent to referral for care among HIV-positive patients
identified through HBHCT in a rural community in Masaka district, Uganda.
METHODS: 28 communities (clusters) were randomly allocated to control (referral
only) and intervention (referral and follow-up counselling) arms (n = 14
clusters/arm). Randomisation was stratified on distance from the district capital
(<=10 km vs > 10 km) and cluster size (larger single village vs combined small
villages), and restricted to ensure balance on selected cluster characteristics.
A list of possible allocations was generated and one randomly selected at a
public ceremony. HBHCT is being offered to all adults (>=18 years), and HIV
positive individuals not yet in care are eligible for enrolment. The intervention
is provided at one and two months post-enrolment. Primary outcomes, assessed 6
months after enrolment, are: the proportion of individuals linking to HIV care
within 6 months of HIV diagnosis and time to linkage. The primary analysis will
be based on individual-level data. DISCUSSION: This study will provide evidence
on the impact of a counselling intervention on linkage to care among adults
identified with HIV infection through HBHCT. Interpretation of the trial outcomes
will be aided by results from an on-going qualitative sub-study.
PMID- 28424796
TI - External data required timely response by the Trial Steering-Data Monitoring
Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial.
AB - The prison-based N-ALIVE pilot trial had undertaken to notify the Research Ethics
Committee and participants if we had reason to believe that the N-ALIVE pilot
trial would not proceed to the main trial. In this paper, we describe how
external data for the third year of before/after evaluation from Scotland's
National Naloxone Programme, a related public health policy, were anticipated by
eliciting prior opinion about the Scottish results in the month prior to their
release as official statistics. We summarise how deliberations by the N-ALIVE
Trial Steering-Data Monitoring Committee (TS-DMC) on N-ALIVE's own interim data,
together with those on naloxone-on-release (NOR) from Scotland, led to the
decision to cease randomization in the N-ALIVE pilot trial and recommend to local
Principal Investigators that NOR be offered to already-randomized prisoners who
had not yet been released.
PMID- 28424798
TI - Hospital Readmissions - Independent Predictors of 30-day Readmissions derived
from a 10 year Database.
AB - Unplanned medical 30 day readmissions place a burden on the provision of acute
hospital services and are increasingly used as quality indicators to assess
quality of care in hospitals. Multivariable logistic regression of a 10 year
database showed that four factors were most strongly associated with early
readmission: Charlson comorbidity index >=1, respiratory disease as a principal
diagnosis, liver disease and alcohol-related illness as an additional diagnosis,
and the number of previous readmissions. Disease and patient-related factors
beyond control of the hospital are the factors most strongly associated with 30
day readmission to hospital, suggesting that this may not be an appropriate
quality indicator.
PMID- 28424799
TI - Role of Psychological Resilience on Health-Outcomes in Hospitalized Patients with
Acute Illness: A Scoping Review.
AB - Recovery from Acute Illness is dependent on severity of illness. We aimed to
investigate whether resilience as the 'ability to bounce back' might also affect
recovery. We conducted a scoping review to identify gaps in the existing
literature. We used emergency care, intensive care, critical care and trauma as
surrogates for acute illness. We mapped synonyms for resilience and selected
'resilience' and 'robustness'. The search was limited to adult patients admitted
to hospitals. We found strong evidence for psychological sequelae of acute
illness but no research focusing specifically on the concepts of resilience or
robustness and no interventional studies in the acute hospital setting. The
concept of resilience might be applicable to unscheduled admissions to hospital.
Measurements and potential interventions require further research.
PMID- 28424800
TI - Progressing care in the Medical High Dependency Unit: unit configurations,
staffing, standards, and daily routine.
AB - There are currently various models of care for provision of high dependency care
for acutely ill medical patients across the UK. Acute Physicians are integral to
the development and progression of this both challenging and rewarding area of
medicine. This article outlines current standards, best evidence, and our own
experience of both setting up and developing a medical high dependency unit
(MHDU).
PMID- 28424797
TI - Magnetoencephalography as a Tool in Psychiatric Research: Current Status and
Perspective.
AB - The application of neuroimaging to provide mechanistic insights into circuit
dysfunctions in major psychiatric conditions and the development of biomarkers
are core challenges in current psychiatric research. We propose that recent
technological and analytic advances in magnetoencephalography (MEG), a technique
that allows measurement of neuronal events directly and noninvasively with
millisecond resolution, provides novel opportunities to address these fundamental
questions. Because of its potential in delineating normal and abnormal brain
dynamics, we propose that MEG provides a crucial tool to advance our
understanding of pathophysiological mechanisms of major neuropsychiatric
conditions, such as schizophrenia, autism spectrum disorders, and the dementias.
We summarize the mechanisms underlying the generation of MEG signals and the
tools available to reconstruct generators and underlying networks using advanced
source-reconstruction techniques. We then surveyed recent studies that have used
MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This was
followed by links with preclinical research that has highlighted possible
neurobiological mechanisms, such as disturbances in excitation/inhibition
parameters, that could account for measured changes in neural oscillations.
Finally, we discuss challenges as well as novel methodological developments that
could pave the way for widespread application of MEG in translational research
with the aim of developing biomarkers for early detection and diagnosis.
PMID- 28424801
TI - Problem-based review: Immune-mediated complications of 'Checkpoint Inhibitors'
for the Acute Physician.
AB - Immunotherapy with 'checkpoint-inhibitors' has significantly improved outcomes
for patients with a range of malignancies. However, significant immune-mediated
toxicities of these therapies are well-described. These immune-mediated
toxicities can affect virtually all organ systems and are potentially fatal. The
timing of onset of the adverse effects is dependent on the organ system affected
and can occur after completion of the treatment. The increasing utilisation of
'checkpoint-inhibitors' means that Acute Physicians are likely to see a number of
immune-mediated complications presenting to the AMU. The fundamental principles
of management of immune-mediated toxicities are early recognition, supportive
treatment, escalating steroid therapy (dependent on the severity of the
toxicity), close liaison with Oncology and specialist organ team input. Research
into the optimal strategies and pathways for the management of immune-mediated
toxicity, as well as increased collaboration between Acute Physicians and
Oncologists, will be necessary.
PMID- 28424802
TI - Evolving sepsis definitions and their impact on Acute Medical Units.
AB - BACKGROUND: There are currently several different definitions for sepsis. This
study looked at what proportion of acute medical admissions were identified by
the different definitions, what correlation they have, and how many patients
would require a review with results in 1 hour. METHODS: Data on 212 admissions
was collected, on time of admission and review, and number of patients with
sepsis by each diagnostic criteria calculated. RESULTS: The NICE criteria
identified 69% of admissions as requiring review within one hour, compared to 6%
with qSOFA and 18% with previous sepsis definitions. The mean time to review was
1hr 18min, and only 50% of patients meeting the NICE criteria were reviewed
within one hour. CONCLUSIONS: The proposed NICE guidance will be challenging to
implement with current resources.
PMID- 28424803
TI - Use of a flumazenil infusion to treat chlordiazepoxide toxicity.
AB - "Alcohol detox" is a common presentation to acute medical services and is usually
managed via standardised guidelines and protocols. We present a case of
chlordiazepoxide toxicity, requiring repeated bolus doses and subsequently 24
hours of an intravenous infusion of flumazenil in response to guideline directed
management of an alcohol withdrawal state. The use of prolonged flumazenil
infusions to treat benzodiazepine toxicity is infrequently described.
Chlordiazepoxide is metabolised in the hepatic microsomal pathway and hepatic
impairment can lead to accumulation of toxic metabolites, which may have been the
explanation for toxicity in this case. In patients at risk of liver dysfunction
we advise the use of benzodiazepines not requiring phase 1 oxidative metabolism,
such as lorazepam or oxazepam.
PMID- 28424804
TI - Acute Medicine Finishing School: Preparing for the next step.
AB - The transition from registrar to consultant in medicine is one that trainees feel
ill prepared for and can be extremely stressful. We devised the concept of an
Acute Medicine "Finishing School" for senior trainees in London training
programmes and ran sessions on CV writing, a simulated consultant interview,
consultant job planning, responding to complaints and an out of hospital
emergency scenario. Our feedback survey indicated that our delegates' confidence
levels in all of the above aspects increased following the sessions. Both formal
and informal feedback highlighted the need and appetite for such a course. By
ensuring trainees are trained and supported through this transition process, we
can ensure the process is a less stressful one.
PMID- 28424805
TI - Cruising through the journey without getting drowned: The saga of a PhD student
in the Netherlands.
AB - Young medical trainees all over the world are encouraged to investigate unknown
areas of medicine that need clarification. This often leads them to undertake a
PhD (Doctor of Philosophy). Being curious, critical, and creative are necessary
competences which enable us to engender scientific research within acute
(internal) medicine. Worldwide, huge numbers of professionals are pursuing a PhD,
with the aim of receiving a 'Doctor'-title. These PhD trajectories vary
distinctly between countries. Since the distances in the scientific world are
getting smaller and it is becoming more easy to work with each other across
borders, it might be interesting to know what it requires to become an academic
'doctor' overseas. Hereby, we provide a concise insight in to the differences
between doing PhD in (acute) medicine in the Netherlands and in the UK.
PMID- 28424818
TI - Dose requirements for idarucizumab reversal of dabigatran in a lethal porcine
trauma model with continuous bleeding.
AB - Idarucizumab is licensed for emergency reversal of dabigatran. A single 5 g dose
is usually sufficient, but higher doses may sometimes be required and optimum
dosing has not been defined. It was the aim of this study to investigate the
effect of idarucizumab, given once or as a split dose, after double trauma in
pigs anticoagulated with dabigatran. Dabigatran etexilate (30 mg/kg bid) was
given to 18 male pigs orally for 3 days. On day 4, animals were randomised 1:1:1
to receive idarucizumab 60+0, 60+60 or 120+0 mg/kg. Doses were administered 15
and 75 minutes after initial liver trauma. At 60 minutes, a second liver injury
was undertaken. Animals were monitored for 5 hours after initial trauma or until
death. Blood loss during the first hour was 990 +/- 109 ml, 988 +/- 84 ml and 964
+/- 75 ml in the 60+0, 60+60 and 120+0 groups, respectively. In the 120+0 and
60+60 groups, total blood loss was 1659 +/- 346 and 1426 +/- 106 ml,
respectively, and survival at 5 hours was 100 %. However, in the 60+0 group,
total blood loss was 3561 +/- 770 ml and survival was 50 %. Analysis of
dabigatran plasma concentrations showed that equimolar concentrations of
idarucizumab are necessary to bind all dabigatran and achieve sufficient thrombin
generation. At sufficient doses, idarucizumab rapidly reduced blood loss and
improved survival in this lethal porcine model of double trauma with dabigatran
anticoagulation. In clinical practice, should bleeding continue after initial
treatment with the approved 5 g dose of idarucizumab, a second dose may
potentially be effective to control bleeding caused by redistribution of unbound
dabigatran.
PMID- 28424819
TI - Plasma microRNAs characterising patients with immune thrombocytopenic purpura.
AB - Altered microRNA (miRNA) expression has been reported in patients with immune
thrombocytopenic purpura (ITP). However, the detailed expression profiling of
cell-free circulating miRNAs in ITP patients has not been fully investigated. In
this study, we aimed to examine plasma miRNAs in ITP patients and evaluate their
diagnostic values. Plasma samples from 74 ITP patients and 58 healthy controls
were obtained and allocated into discovery, validation, and therapy-response
sets. Initial screen with a miRNA microarray assay identified 23 miRNAs with
different levels between ITP patients and healthy controls (>1.5-fold changes;
p<0.01). Subsequent quantitative real-time PCR confirmed eight up-regulated
miRNAs (miR-320c, miR-642b-3p, miR-1275, miR-3141, miR-4270, miR-4499, miR-4739
and miR-6126) and three down-regulated miRNAs (miR-144-3p, miR-1281 and miR-3162
3p) in ITP patients. The levels of these circulating miRNAs varied, depending on
ITP subtypes, i.e. newly-diagnosed, persistent and chronic ITP, and between
treatment responders and non-responders. In receiver operator characteristic
analysis, 10 miRNAs had positive diagnostic values (p<0.05) when tested
individually. The diagnostic value improved when the miRNAs were analysed as a
panel or together with the analysis of anti-platelet autoantibodies. Plasma miR
3162-3p levels were also found to positively correlate with platelet counts in
ITP patients (r=0.338, p=0.01). Our results indicate that plasma miRNA profiles
are altered in ITP patients and that the differentially expressed miRNAs may be
used as biomarkers to improve the diagnosis of ITP.
PMID- 28424820
TI - Microparticles during long-term follow-up after acute myocardial infarction.
Association to atherosclerotic burden and risk of cardiovascular events.
AB - Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs)
and monocytes (MMPs), and in acute myocardial infarction (MI), there is an
increase of MPs in the culprit artery. In this study MPs were evaluated in whole
blood in 105 patients with MI at five time-points during a two-year follow-up
(FU). Patients with non-ST-elevated MI had higher concentrations of CD41+MPs
compared to ST-elevated MI patients (p=0.024). The concentrations of PMPs in
whole blood increased during the time period (p<0.001), but no significant change
over time was found for EMPs and MMPs. CD62P+MP counts were higher in MI patients
with diabetes (p=0.020), and patients with hypertension had increased levels of
CD14+MPs (p=0.004). The amount of CD62P+TF+MPs increased significantly during FU
(p<0.001). Patients with atherosclerosis in three arterial beds, i. e. coronary,
carotid and peripheral arteries, had lower concentrations of CD62P+TF+MPs
(p=0.035) and CD144+TF+MPs (p=0.004) compared to patients with atherosclerosis in
one or two arterial beds. Higher concentrations of CD62P+MPs early after MI were
associated with an increased risk of cardiovascular events during FU, hazard
ratio 3.32 (95 %CI1.20-9.31). Only small variations in PMP, EMP and MMP
concentrations were found during long-term FU after MI and their levels seem to
reflect the underlying cardiovascular disease rather than the acute MI. PMPs
expressing P-selectin might be a promising biomarker for predicting future
cardiovascular events, but further studies are needed to confirm these results.
PMID- 28424821
TI - NOACs for treatment of venous thromboembolism in clinical practice.
AB - Randomised controlled trials have provided important information on the efficacy
and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) for
treatment of venous thromboembolism (VTE), leading to registration and increasing
use in clinical practice. Many questions remain to be answered, and observational
studies are often more suitable for answering "real-world" questions than
randomised controlled trials. Patient satisfaction, quality of life, and
adherence and persistence in clinical practice with the drug regimen can only be
assessed with an open-label design. Evaluation of risk for long-term sequelae of
the disease requires much longer follow-up than is possible in registration
trials. Treatment patterns and utilisation of health care resources can be
assessed from observations in the clinical practice setting. We will review
published as well as currently active observational studies with NOACs in VTE,
with or without a comparator anticoagulant. These studies are based on cohorts of
different sizes, registries, or administrative health care databases. We will
also discuss some limitations in analysis and interpretation of observational
studies.
PMID- 28424822
TI - Rapid non-contrast magnetic resonance imaging for post appendectomy intra
abdominal abscess in children.
AB - BACKGROUND: Acute appendicitis, especially if perforated at presentation, is
often complicated by postoperative abscess formation. The detection of a
postoperative abscess relies primarily on imaging. This has traditionally been
done with contrast-enhanced computed tomography. Non-contrast magnetic resonance
imaging (MRI) has the potential to accurately detect intra-abdominal abscesses,
especially with the use of diffusion-weighted imaging (DWI). OBJECTIVE: To
evaluate our single-center experience with a rapid non-contrast MRI protocol
evaluating post-appendectomy abscesses in children with persistent postsurgical
symptoms. MATERIALS AND METHODS: In this retrospective, institutional review
board-approved study, all patients underwent a clinically indicated non-contrast
1.5- or 3-Tesla abdomen/pelvis MRI consisting of single-shot fast spin echo,
inversion recovery and DWI sequences. All MRI studies were reviewed by two
blinded pediatric radiologists to identify the presence of a drainable fluid
collection. Each fluid collection was further characterized as accessible or not
accessible for percutaneous or transrectal drainage. Imaging findings were
compared to clinical outcome. RESULTS: Seven of the 15 patients had a clinically
significant fluid collection, and 5 of these patients were treated with
percutaneous drain placement or exploratory laparotomy. The other patients had a
phlegmon or a clinically insignificant fluid collection and were discharged home
within 48 h. CONCLUSION: Rapid non-contrast MRI utilizing fluid-sensitive and DWI
sequences can be used to identify drainable fluid collections in post
appendectomy patients. This protocol can be used to triage patients between
conservative management vs. abscess drainage without oral/intravenous contrast or
exposure to ionizing radiation.
PMID- 28424823
TI - [Coma in the emergency room].
AB - Coma of unknown origin (CUO) is a frequent unspecific emergency symptom
associated with a high mortality. A fast diagnostic work-up is essential given
the wide spectrum of underlying diagnoses that are made up of approximately 50%
primary central nervous system (CNS) pathologies and approximately 50%
extracerebral, almost exclusively internal medical causes. Despite the high
mortality associated with this symptom, there are currently no generally accepted
management guidelines for adult patients presenting with CUO. We propose an
interdisciplinary standard operating procedure (SOP) for patients with acute CUO
as has been established in our maximum care hospital. The SOP is triggered by
simple triage criteria that are sufficient to identify CUO patients before
arrival in hospital. The in-hospital response team is led by a neurologist.
Collaboration with nursing staff, internal medicine, anesthesiology, neurosurgery
and trauma surgery is organized along structured pathways that include
standardized laboratory tests, including cerebrospinal fluid (CSF), toxicology,
computed tomography (CT) and CT angiography imaging (CTA). Our data suggest that
neurologists and internists need to be placed at the beginning of the diagnostic
work-up. Imaging should not just be carried out depending on the clinical
syndrome because sensitivity, specificity and inter-rater reliability of the
latter are not sufficient and because in many cases, multiple pathologies can be
detected that could each explain CUO alone. Clinical examination, imaging and
laboratory testing should be regarded as components of an integrative diagnostic
approach and the final aetiological classification should only be made after the
diagnostic work-up is complete.
PMID- 28424824
TI - Resistin and NGAL are associated with inflammatory response, endothelial
activation and clinical outcomes in sepsis.
AB - OBJECTIVE AND DESIGN: Resistin and neutrophil gelatinase-associated lipocalin
(NGAL) are upregulated in circulating leucocytes in sepsis, but the significance
of this is uncertain. We evaluated associations between Resistin and NGAL with
endothelial cell activation and clinical outcomes in a prospective observational
study in the Emergency Department (ED). METHODS: Serum levels of Resistin, NGAL,
inflammatory cytokines (IL-6, IL-10) and soluble endothelial adhesion molecules
(VCAM-1, ICAM-1) were measured at defined time points up to 24 h. Patterns and
relationships between markers were investigated using linear mixed regression
models. Predictive values for clinical outcomes for markers at enrollment were
assessed by logistic regression and receiver operator characteristic (ROC)
curves. RESULTS: 186 participants (89 septic-shock, 69 sepsis, 28 uncomplicated
infection) were compared with 29 healthy controls. Median Resistin and NGAL were
higher in uncomplicated infection compared to controls, and in septic shock
compared to non-shock sepsis. Resistin and NGAL correlated with IL-6 and IL-10,
with VCAM-1 and ICAM-1, and with organ failure. Resistin and NGAL were associated
with septic shock but had limited predictive utility for mortality. CONCLUSION:
Resistin and NGAL correlate with expression of endothelial cell adhesion
molecules in sepsis. Further evaluation of the role of Resistin and NGAL in
sepsis pathogenesis is warranted.
PMID- 28424825
TI - A Magnetized Nanoparticle Based Solid-Phase Extraction Procedure Followed by
Inductively Coupled Plasma Atomic Emission Spectrometry to Determine Arsenic,
Lead and Cadmium in Water, Milk, Indian Rice and Red Tea.
AB - A sensitive and simple method using magnetic multi-walled carbon nanotube (MWCNTs
Fe3O4 MNP), as the adsorbent, has been successfully developed for extraction and
pre-concentration of arsenic, lead and cadmium with detection by inductively
coupled plasma-atomic emission spectroscopy (ICP-AES). The nanosorbent was
characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray
diffraction pattern (XRD), vibrating sample magnetometer (VSM) and transmission
electron microscopy (TEM). The key factors affecting the signal intensity such as
pH, adsorbent amount, etc. were investigated. Under optimal conditions, the
limits of detection (three-time of signal to noise ratio, S/N 3) were 0.3, 0.6,
0.3 ng/mL for arsenic, lead and cadmium, respectively. Application of the
adsorbent was investigated by the analysis of water, milk, Indian rice and red
tea. The experimental data was analyzed and obeyed Langmuir and Freundlich
adsorption models. The kinetic data was fitted to the pseudo-second-order model.
Thermodynamic studies revealed the feasibility and exothermic nature of the
system.
PMID- 28424826
TI - Synergizing 13C Metabolic Flux Analysis and Metabolic Engineering for Biochemical
Production.
AB - Metabolic engineering of industrial microorganisms to produce chemicals, fuels,
and drugs has attracted increasing interest as it provides an environment
friendly and renewable route that does not depend on depleting petroleum sources.
However, the microbial metabolism is so complex that metabolic engineering
efforts often have difficulty in achieving a satisfactory yield, titer, or
productivity of the target chemical. To overcome this challenge, 13C Metabolic
Flux Analysis (13C-MFA) has been developed to investigate rigorously the cell
metabolism and quantify the carbon flux distribution in central metabolic
pathways. In the past decade, 13C-MFA has been widely used in academic labs and
the biotechnology industry to pinpoint the key issues related to microbial-based
chemical production and to guide the development of the appropriate metabolic
engineering strategies for improving the biochemical production. In this chapter
we introduce the basics of 13C-MFA and illustrate how 13C-MFA has been applied to
synergize with metabolic engineering to identify and tackle the rate-limiting
steps in biochemical production.
PMID- 28424828
TI - [On the treatment of candiduria and nitroxoline sensitivity of Candida isolates].
PMID- 28424827
TI - Fluorescence Spectroscopy for the Monitoring of Food Processes.
AB - Different analytical techniques have been used to examine the complexity of food
samples. Among them, fluorescence spectroscopy cannot be ignored in developing
rapid and non-invasive analytical methodologies. It is one of the most sensitive
spectroscopic approaches employed in identification, classification,
authentication, quantification, and optimization of different parameters during
food handling, processing, and storage and uses different chemometric tools.
Chemometrics helps to retrieve useful information from spectral data utilized in
the characterization of food samples. This contribution discusses in detail the
potential of fluorescence spectroscopy of different foods, such as dairy, meat,
fish, eggs, edible oil, cereals, fruit, vegetables, etc., for qualitative and
quantitative analysis with different chemometric approaches.
PMID- 28424829
TI - [MRI of the prostate].
AB - New clinical and technological advances in the field of magnetic resonance
imaging (MRI) and targeted image-guided biopsy techniques have significantly
improved the detection, localization and staging as well as active surveillance
of prostate cancer in recent years. Multiparametric MRI (mpMRI) is currently the
main imaging technique for the detection, characterization and diagnostics of
metastasizing prostate cancer and is of high diagnostic importance for local
staging within the framework of the detection of prostate cancer.
PMID- 28424830
TI - [When is a nonsurgical approach possible for metastatic primary tumors and lymph
node metastases of the urinary bladder and prostate?]
AB - For metastatic carcinomas of the urinary bladder and prostate, systemic therapy
is of primary importance. Due to technological advances in radiation oncology
such as stereotactic radiotherapy, intensity-modulated radiotherapy, interstitial
radiotherapy, and the combination of radiotherapy and chemotherapy, pelvic
irradiation can nowadays be carried out effectively and without the risk of major
side effects. New data from other tumor entities and retrospective analyses
suggest that the use of these technologies can lead to a clinical benefit in
terms of improvement in quality of life, local control, and overall survival. For
the time being, the decision to administer radiotherapy to the pelvic region
should be made on an individual basis. Retrospective analyses of data from
prostate carcinomas in particular are currently being planned. This review
article introduces potential indications which are supported with real patient
examples and discusses future developments giving an overview of the literature
and referring to data from prospective randomized trials.
PMID- 28424831
TI - [Recurrent and catheter-associated urinary tract infections : Prophylaxis and
prevention].
AB - Urinay tract infection (UTI) as one of the most frequent bacterial infections in
humans is of utmost relevance. Because of the rising prevalence of antimicrobial
resistance, urinalysis should always include urine culture and a resistogram in
order to avoid an unspecific selection and overuse of antibiotics. Prevention of
recurrent UTI must first of all rule out predisposing uropathogenic conditions.
Nowadays, a great variety of drugs, behavioral, and supportive treatment options
can effectively minimize UTI recurrence. The growing importance of vaccines
(immunotherapy), probiotics (lactobacilli), and standardized herbal preparations
meets the need of reducing antibiotic use and the development of antimicrobial
resistance. Around 80% of all nosocomial UTIs (nUTIs) are associated with
indwelling urinary catheters. It is estimated that up to 70% of all nUTIs
occurring in Germany may be avoided by using appropriate preventative measures.
Therefore, profound knowledge about the basics of catheter-associated nUTIs and
the correct management of urinary catheters are of utmost individual and
socioeconomic importance.
PMID- 28424832
TI - Setting up a community-based cervical screening service in a low-income country:
a pilot study from north-western Tanzania.
AB - OBJECTIVES: To report the results of a pilot study for a service for cervical
cancer screening and diagnosis in north-western Tanzania. METHODS: The pilot
study was launched in 2012 after a community-level information campaign. Women
aged 15-64 years were encouraged to attend the district health centres. Attendees
were offered a conventional Pap smear and a visual inspection of the cervix with
acetic acid (VIA). RESULTS: The first 2500 women were evaluated. A total of 164
women (detection rate 70.0/1000) were diagnosed with high-grade cervical
intraepithelial neoplasia and invasive cervical cancer. The performance of VIA
was comparable to that of Pap smear. The district of residence, a history of
untreated sexually transmitted disease, an HIV-negative status (inverse
association), and parity were independently associated with the detected
prevalence of disease. The probability of invasive versus preinvasive disease was
lower in HIV-positive women and in women practicing breast self-examination.
CONCLUSIONS: The diagnostic procedure had an acceptable level of quality. Factors
associated with the detected prevalence of disease will allow for a more targeted
promotion of the service. Cervical screening should be coordinated with sexually
transmitted disease and HIV infection control activities.
PMID- 28424833
TI - Cannabis-related hippocampal volumetric abnormalities specific to subregions in
dependent users.
AB - RATIONALE: Cannabis use is associated with neuroanatomical alterations in the
hippocampus. While the hippocampus is composed of multiple subregions, their
differential vulnerability to cannabis dependence remains unknown. OBJECTIVES:
The objective of the study is to investigate gray matter alteration in each of
the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields
CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence.
METHODS: A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and
39 dependent (CB-dep) cannabis users were recruited. We investigated group
differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep
users. We further explored the association between CB use variables (age of onset
of regular use, monthly use, lifetime use) and hippocampal subregions in CB
nondep and CB-dep users separately. RESULTS: The CA1, CA2/3, CA4/DG, as well as
total hippocampal gray matter were reduced in volume in CB-dep but not in CB
nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also
negatively associated with lifetime cannabis use in CB-dep users. CONCLUSIONS:
Our results suggest a regionally and dependence-specific influence of cannabis
use on the hippocampus. Hippocampal alteration in cannabis users was specific to
the CA and DG regions and confined to dependent users.
PMID- 28424834
TI - Effect of prior foot shock stress and Delta9-tetrahydrocannabinol, cannabidiolic
acid, and cannabidiol on anxiety-like responding in the light-dark emergence test
in rats.
AB - RATIONALE: Cannabis is commonly used by humans to relieve stress. OBJECTIVES AND
METHODS: Here, we evaluate the potential of intraperitoneally (i.p.) administered
Delta9-tetrahydrocannabiol (THC) and cannabidiolic acid (CBDA, the precursor of
cannabidiol [CBD]) to produce dose-dependent effects on anxiety-like responding
in the light-dark (LD) emergence test of anxiety-like responding in rats, when
administered acutely or chronically (21 days). As well, we evaluate the potential
of THC, CBDA, and CBD to reduce anxiogenic responding produced by foot shock (FS)
stress 24 h prior to the LD test. RESULTS: In the absence of the explicit FS
stressor, THC (1 and 10 mg/kg) produced anxiogenic-like responding when
administered acutely or chronically, but CBDA produced neither anxiogenic- nor
anxiolytic-like responding. Administration of FS stress 24 h prior to the LD test
enhanced anxiogenic-like responding (reduced time spent and increased latency to
enter the light compartment) in rats pretreated with either vehicle (VEH) or THC
(1 mg/kg); however, administration of CBDA (0.1-100 MUg/kg) or CBD (5 mg/kg)
prevented the FS-induced anxiogenic-like responding (an anxiolytic-like effect).
The 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist, WAY100635, reversed
CBDA's anxiolytic effect (1 MUg/kg). Combining an anxiolytic dose of CBDA (1
MUg/kg) or CBD (5 mg/kg) with an anxiogenic dose of THC (1 mg/kg) did not modify
THC's anxiogenic effect. CONCLUSION: These results suggest the anxiolytic effects
of CBDA and CBD may require the presence of a specific stressor.
PMID- 28424835
TI - [Future of emergency medicine in Germany 2.0].
AB - In 2003 an article on the future of prehospital emergency medicine in Germany was
published in the journal Der Anaesthesist. Emergency medicine in Germany, which
at that time was almost exclusively defined as prehospital emergency rescue, has
evolved and now in-hospital domains have increasingly moved into the focus. At
that time, the primary goal was to connect prehospital management with a smooth
transition to hospital admission and further care in the hospital and to further
optimize the rescue chain from the actual emergency through to causative
treatment. Now after 15 years, the authors have critically assessed the
development postulated in 2003 and reevaluated it. Which aspects could be
developed further and become firmly established, what is still open and which
questions in preclinical and clinical emergency treatment of the population will
occupy us in the coming 15 years? With a critical eye to the past, the present
contribution aims to capture the essential and new topics and open questions and
provide a fresh perspective for the future of emergency medicine. Regulation at
the state level or even lower levels of government often stand in contrast to
more sweeping and economically effective approaches at the federal level.
Prehospital emergency medicine in Germany is on the whole well-positioned with
respect to facilities and personnel; however, as far as the economic situation
and the utilization of available systems are concerned, there is still
substantial room for improvement.
PMID- 28424836
TI - [On the occasion of Swen Malte John's 60th birthday].
PMID- 28424837
TI - Arsenic, Cadmium, Chromium, Lead, Mercury and Selenium Concentrations in Pine
Snakes (Pituophis melanoleucus) from the New Jersey Pine Barrens.
AB - Top trophic level predators are at risk from bioaccumulation of heavy metals from
their prey. Using nondestructively collected tissues as a method of assessing
metal concentrations in snakes is useful for populations that are threatened or
declining. This paper reports concentrations of arsenic (As), cadmium (Cd),
chromium (Cr), lead (Pb), mercury (Hg), and selenium (Se) in tissues of Northern
pine snakes (Pituophis melanoleucus) from the New Jersey Pine Barrens, a
relatively pristine, undisturbed habitat. We also determined if skin is an
appropriate indicator of internal concentrations and identified the factors
(tissue, year of collection, length, sex) that might explain variations in metal
concentrations. Because they can grow to 2-m long and live for 25 years, we
suggest that these snakes might accumulate heavy metals. Multiple regression
models were significant, explaining 16% (lead) to 61% (mercury) of variation by
tissue type. For mercury and chromium, size also was significant. The highest
concentrations were in liver and kidney for all metals, except chromium and lead.
Mercury concentrations in tissues were within the range reported for other snakes
and were below effects concentrations in reptiles. The concentrations in skin
were correlated with all internal tissues for mercury and for all internal
tissues except heart for cadmium. These data show that shed skin can be used as
an indicator of metals in pine snakes and that, at present, concentrations of
heavy metals in this population are within the range of those found in other
snake species from uncontaminated sites.
PMID- 28424838
TI - Improved oncologic outcome with chemoradiotherapy followed by surgery in
unresectable intrahepatic cholangiocarcinoma.
AB - PURPOSE: To investigate the ability of chemoradiotherapy (CRT) to down-stage
unresectable intrahepatic cholangiocarcinoma (IHCC) to resectable lesions, as
well as the factors associated with achieving such down-staging. METHODS: The
study cohort comprised 120 patients diagnosed with stage I-IVA IHCC between 2001
and 2012. Of these patients, 56 underwent surgery and 64 received CRT as their
initial treatment. The rate of curative resections for patients who received CRT
was assessed, and the locoregional failure-free survival (LRFFS) and overall
survival (OS) rates of these patients were compared to those of patients who
underwent CRT alone. RESULTS: Median follow-up was 36 months. A partial response
after CRT was observed in 25% of patients, whereas a biologic response (a >70%
decrease of CA19-9) was observed in 35%. Eight patients (12.5%) received curative
resection after CRT and showed significantly improved LRFFS and OS compared to
those treated with CRT alone (3-year LRFFS: 50 vs. 15.7%, respectively, p = 0.03;
3-year OS: 50 vs. 11.2%, respectively, p = 0.012); these rates were comparable to
those of patients who received initial surgery. Factors associated with curative
surgery after CRT were gemcitabine administration, higher radiotherapy dose
(biological effective dose >=55 Gy with alpha/beta = 10), and a >70% reduction of
CA19-9. CONCLUSION: Upfront CRT could produce favorable outcomes by converting
unresectable lesions to resectable tumors in selected patients. Higher
radiotherapy doses and gemcitabine-based chemotherapy yielded a significant
reduction of CA19-9 after CRT; patients with these characteristics had a greater
chance of curative resection and improved OS.
PMID- 28424839
TI - Reirradiation of recurrent node-positive non-small cell lung cancer after
previous stereotactic radiotherapy for stage I disease : A multi-institutional
treatment recommendation.
AB - BACKGROUND: Practice guidelines have been developed for early-stage and locally
advanced non-small cell lung cancer (NSCLC). However, many common clinical
scenarios still require individualized decision making. This is true for
locoregional relapse after initial stereotactic radiotherapy (stereotactic body
radiation therapy or stereotactic ablative radiotherapy; SBRT or SABR), an
increasingly utilized curative treatment option for stage I NSCLC. METHODS: A
consortium of expert radiation oncologists was established with the aim of
providing treatment recommendations. In this scenario, a case was distributed to
six radiation oncologists who provided their institutions' treatment
recommendations. In this case, a patient developed local and mediastinal relapse
after SABR (45 Gy, 3 fractions), comparable to the tumor burden in de novo stage
IIIA NSCLC. Treatment recommendations were tabulated and a consensus conclusion
was developed. RESULTS: Three institutions recommended evaluation for surgery. If
the patient was not a surgical candidate, and/or refused surgery, definitive
chemoradiation was recommended, including retreating the primary to full dose.
European participants were more in favor of a non-surgical approach. None of the
participants were reluctant to prescribe reirradiation, but two institutions
prescribed doses lower than 60 Gy. Platinum-based doublets together with
intensity-modulated radiotherapy were preferred. CONCLUSION: The institutional
recommendations reflect the questions and uncertainties discussed in current
stage III guidelines. All institutions agreed that previous SABR is not a
contraindication for salvage chemoradiation. In the absence of high-quality
prospective trials for recurrent NSCLC, all treatment options recommended in
current guidelines for stage III disease can be considered in clinical scenarios
such as this.
PMID- 28424840
TI - Reirradiation for recurrent head and neck cancers using charged particle or
photon radiotherapy.
AB - OBJECTIVE: To examine the outcomes of reirradiation for recurrent head and neck
cancers using different modalities. METHODS: This retrospective study included 26
patients who received charged particle radiotherapy (CP) and 150 who received
photon radiotherapy (117 CyberKnife radiotherapy [CK] and 36 intensity-modulated
radiotherapy [IMRT]). Inverse probability of treatment weighting (IPTW) involving
propensity scores was used to reduce background selection bias. RESULTS: Higher
prescribed doses were used in CP than photon radiotherapy. The 1-year overall
survival (OS) rates were 67.9% for CP and 54.1% for photon radiotherapy (p =
0.15; 55% for CK and 51% for IMRT). In multivariate Cox regression, the
significant prognostic factors for better survival were nasopharyngeal cancer,
higher prescribed dose, and lower tumor volume. IPTW showed a statistically
significant difference between CP and photon radiotherapy (p = 0.04). The local
control rates for patients treated with CP and photon radiotherapy at 1 year were
66.9% (range 46.3-87.5%) and 67.1% (range 58.3-75.9%), respectively. A total of
48 patients (27%) experienced toxicity grade >=3 (24% in the photon radiotherapy
group and 46% in the CP group), including 17 patients with grade 5 toxicity.
Multivariate analysis revealed that younger age and a larger planning target
volume (PTV) were significant risk factors for grade 3 or worse toxicity.
CONCLUSION: CP provided superior survival outcome compared to photon
radiotherapy. Tumor volume, primary site (nasopharyngeal), and prescribed dose
were identified as survival factors. Younger patients with a larger PTV
experienced toxicity grade >=3.
PMID- 28424841
TI - Dosimetric predictors of radiation-induced pericardial effusion in esophageal
cancer.
AB - PURPOSE: To evaluate the dose-volume parameters of the pericardium and heart in
order to reduce the risk of radiation-induced pericardial effusion (PE) and
symptomatic PE (SPE) in esophageal cancer patients treated with concurrent
chemoradiotherapy. METHODS: In 86 of 303 esophageal cancer patients, follow-up CT
was obtained at least 24 months after concurrent chemoradiotherapy. Correlations
between clinical factors, including risk factors for cardiac disease, dosimetric
factors, and the incidence of PE and SPE after radiotherapy were analyzed using
Cox proportional hazard regression analysis. Significant dosimetric factors with
the highest hazard ratios were investigated using zones separated according to
their distance from esophagus. RESULTS: PE developed in 49 patients. Univariate
analysis showed the mean heart dose, heart V5-V55, mean pericardium dose, and
pericardium V5-V50 to all significantly affect the incidence of PE. Additionally,
body surface area was correlated with the incidence of PE in multivariate
analysis. Grade 3 and 4 SPE developed in 5 patients. The pericardium V50 and
pericardium D10 significantly affected the incidence of SPE. The pericardium V50
in patients with SPE ranged from 17.1 to 21.7%. Factors affecting the incidence
of SPE were the V50 of the pericardium zones within 3 cm and 4 cm of the
esophagus. CONCLUSION: A wide range of radiation doses to the heart and
pericardium were related to the incidence of PE. A pericardium V50 <= 17% is
important to avoid symptomatic PE in esophageal cancer patients treated with
concurrent chemoradiotherapy.
PMID- 28424842
TI - WY-14643 and 9-cis-retinoic acid induce IRS-2/PI 3-kinase signalling pathway and
increase glucose transport in human skeletal muscle cells: differential effect in
myotubes from healthy subjects and Type 2 diabetic patients.
AB - AIMS/HYPOTHESIS: To determine the effects of peroxisome proliferator-activated
receptor alpha (PPARalpha) and retinoid X receptor (RXR) agonists on insulin
action, we investigated the effects of Wy-14643 and 9-cis-retinoic acid (9-cis
RA) on insulin signalling and glucose uptake in human myotubes. METHODS: Primary
cultures of differentiated human skeletal muscle cells, established from healthy
subjects and Type 2 diabetic patients, were used to study the effects of Wy-14643
and 9-cis-RA on the expression and activity of proteins involved in the insulin
signalling cascade. Glucose transport was assessed by measuring the rate of [3H]2
deoxyglucose uptake. RESULTS: Wy-14643 and 9-cis-RA increased IRS-2 and p85alpha
phosphatidylinositol 3-kinase (PI 3-kinase) mRNA and protein expression in
myotubes from non-diabetic and Type 2 diabetic subjects. This resulted in
increased insulin stimulation of protein kinase B phosphorylation and increased
glucose uptake in cells from control subjects. Myotubes from diabetic patients
displayed marked alterations in the stimulation by insulin of the IRS-1/PI 3
kinase pathway. These alterations were associated with blunted stimulation of
glucose transport. Treatment with Wy-14643 and 9-cis-RA did not restore these
defects but increased the basal rate of glucose uptake.
CONCLUSIONS/INTERPRETATION: These results demonstrate that PPARalpha and RXR
agonists can directly affect insulin signalling in human muscle cells. They also
indicate that an increase in the IRS-2/PI 3-kinase pathway does not overcome the
impaired stimulation of the IRS-1-dependent pathway and does not restore insulin
stimulated glucose uptake in myotubes from Type 2 diabetic patients.
PMID- 28424843
TI - EASD News Section July 2004.
PMID- 28424844
TI - Microbial reductive dehalogenation of trihalomethanes by a Dehalobacter
containing co-culture.
AB - Trihalomethanes such as chloroform and bromoform, although well-known as a
prominent class of disinfection by-products, are ubiquitously distributed in the
environment due to widespread industrial usage in the past decades. Chloroform
and bromoform are particularly concerning, of high concentrations detected and
with long half-lives up to several hundred days in soils and groundwater. In this
study, we report a Dehalobacter- and Desulfovibrio-containing co-culture that
exhibits dehalogenation of chloroform (~0.61 mM) to dichloromethane and bromoform
(~0.67 mM) to dibromomethane within 10-15 days. This co-culture was further found
to dechlorinate 1,1,1-trichloroethane (1,1,1-TCA) (~0.65 mM) to 1,1
dichloroethane within 12 days. The Dehalobacter species present in this co
culture, designated Dehalobacter sp. THM1, was found to couple growth with
dehalogenation of chloroform, bromoform, and 1,1,1-TCA. Strain THM1 harbors a
newly identified reductive dehalogenase (RDase), ThmA, which catalyzes
chloroform, bromoform, and 1,1,1-TCA dehalogenation. Additionally, based on the
sequences of thmA and other identified chloroform RDase genes, ctrA, cfrA, and
tmrA, a pair of chloroform RDase gene-specific primers were designed and
successfully applied to investigate the chloroform dechlorinating potential of
microbial communities. The comparative analysis of chloroform RDases with
tetrachloroethene RDases suggests a possible approach in predicting the substrate
specificity of uncharacterized RDases in the future.
PMID- 28424845
TI - The regulatory role of the transcription factor Crz1 in stress tolerance,
pathogenicity, and its target gene expression in Metarhizium acridum.
AB - In fungi, the Ca2+/calcineurin signaling pathway is critical in mediating growth,
morphology, stress responses, and pathogenicity. Crz1 is a calcineurin-responsive
zinc finger transcription factor. Here, MaCrz1 was identified and functionally
characterized in the entomopathogenic fungus Metarhizium acridum by
characterization of a targeted gene knockout strain. Conidia of the DeltaMacrz1
mutant were aberrant in cell surface features and lacked the characteristic
hydrophobic rodlet layer, and the mutant displayed increased sensitivity to
oxidative stress, cell wall perturbing agents, heat stress, and ultraviolet
irradiation as compared to the wild-type and complemented strains. Insect
bioassay using locusts revealed decreased virulence for the DeltaMaCrz1 mutant,
with defects in the ability of the mutant to penetrate the host cuticle. The
DeltaMaCrz1 mutant also showed greatly reduced chitin and beta-1,3-glucan level
in the cell wall. Transcriptomic profiling revealed genes involved in cell wall
synthesis, conidiation, stress tolerance, and calcium transport that were
downregulated in the DeltaMaCrz1 mutant. Our results demonstrate that MaCrz1
plays important roles in stress susceptibility and pathogenicity, and provides
clues as to the genes and pathways targeted by the transcription factor.
PMID- 28424846
TI - Summary of the preservation techniques and the evolution of the anammox bacteria
characteristics during preservation.
AB - The anaerobic ammonium oxidation (anammox) process is a promising wastewater
treatment method for biological nitrogen removal. A sufficient amount of active
anammox sludge as a seed is crucial to the fast establishment and stability of
the anammox process. Anammox bacteria is a kind of microorganism which is
sensitive to the environmental conditions, e.g., oxygen, temperature. The optimum
temperature and pH for the growth of the anammox bacteria are 30-40 degrees C
and 6.7-8.3. A proper preservation technique allows fast start-up of the anammox
process, overcoming the long doubling time of anammox biomass. The preservation
of the anammox sludge is influenced by various factors, e.g., preservation
techniques, duration, temperature, substrates, and protective agents. During
preservation, the characteristics of the anammox biomass, including the
bioactivity, heme c content, extracellular polymeric substances (EPS), and sludge
morphology, change with time. The optimum preservation technique is not
invariable and it depends on the purpose of preservation (precedence of
bioactivity or quantity), the bacterial community, and other parameters. It is
important for the preserved anammox biomass to achieve reactivation so that
stable anammox reactors can be established as soon as possible. However, because
the preservation process is complicated, the knowledge regarding preservation is
far from complete, and much future work will be required to increase the
understanding of preservation.
PMID- 28424847
TI - Characterization of microtubule buckling in living cells.
AB - Microtubules are filamentous biopolymers involved in essential biological
processes. They form key structures in eukaryotic cells, and thus it is very
important to determine the mechanisms involved in the formation and maintenance
of the microtubule network. Microtubule bucklings are transient and localized
events commonly observed in living cells and characterized by a fast bending and
its posterior relaxation. Active forces provided by molecular motors have been
indicated as responsible for most of these rapid deformations. However, the
factors that control the shape amplitude and the time scales of the rising and
release stages remain unexplored. In this work, we study microtubule buckling in
living cells using Xenopus laevis melanophores as a model system. We tracked
single fluorescent microtubules from high temporal resolution (0.3-2 s) confocal
movies. We recovered the center coordinates of the filaments with 10-nm precision
and analyzed the amplitude of the deformation as a function of time. Using
numerical simulations, we explored different force mechanisms resulting in
microtubule bending. The simulated events reproduce many features observed for
microtubules, suggesting that a mechanistic model captures the essential
processes underlying microtubule buckling. Also, we studied the interplay between
actively transported vesicles and the microtubule network using a two-color
technique. Our results suggest that microtubules may affect transport indirectly
besides serving as tracks of motor-driven organelles. For example, they could
obstruct organelles at microtubule intersections or push them during filament
mechanical relaxation.
PMID- 28424848
TI - Glycemic control, mortality, secondary infection, and hypoglycemia in critically
ill pediatric patients: a systematic review and network meta-analysis of
randomized controlled trials.
PMID- 28424849
TI - Ultrasound evaluation of the ulnar collateral ligament of the elbow: Which method
is most reproducible?
AB - INTRODUCTION: The ulnar collateral ligament (UCL) is an important medial
stabilizer of the elbow, particularly in overhead-throwing athletes. However,
there is no universally accepted method for evaluating UCL thickness with
ultrasound (US). OBJECTIVE: To assess reproducibility of previously published
methods, as well as a modified technique, for evaluating the UCL via US. We
hypothesize that a modified technique would show greater reproducibility.
MATERIAL AND METHODS: Using US, the thickness of the UCL in 50 volunteers was
measured by two musculoskeletal trained radiologists using two different
measurement techniques. The techniques utilized were as described by Nazarian and
Jacobson/Ward (JW). Technique measurements were evaluated using interclass
correlation coefficients (ICC) to determine the reproducibility of each method.
Twenty-eight of the subjects also underwent measurement via a modified JW
technique, measured perpendicular to the ligament rather than the frame of
imaging. This technique was also evaluated with ICC values. RESULTS: The ICC
value for the Nazarian technique was 0.82 (very good) and 0.51 (moderate) for the
JW technique. When using the modified JW technique, we found an ICC value of 0.84
(very good). Mean ligament thickness was greatest with the Nazarian technique,
6.41 mm, with the JW technique measuring 1.86 mm and the modified technique
measuring 1.38 mm. CONCLUSION: US assessment of UCL thickness by all three
measurement techniques are reproducible. The JW technique had less interobserver
agreement when compared to the Nazarian method, whereas the modified JW technique
had greater reproducibility compared to the JW technique and similar to the
Nazarian technique.
PMID- 28424850
TI - Incidence and MRI characterization of the spectrum of posterolateral corner
injuries occurring in association with ACL rupture.
AB - OBJECTIVE: To determine the incidence and MRI characteristics of the spectrum of
posterolateral corner (PLC) injuries occurring in association with anterior
cruciate ligament (ACL) rupture. MATERIALS AND METHODS: We carried out a level
IV, retrospective case series study. All patients clinically diagnosed with an
ACL rupture between July 2015 and June 2016 who underwent MRI of the knee were
included in the study. In addition to standard MRI knee reporting, emphasis was
placed on identifying injury to the PLC and a description of involvement of these
structures by two musculoskeletal radiologists. Association with PLC involvement
was sought with concomitant injuries using correlation analysis and logistic
regression. RESULTS: One hundred sixty-two patients with MRI following ACL
rupture were evaluated. Thirty-two patients (19.7%) had an injury to at least one
structure of the PLC, including the inferior popliteomeniscal fascicle (n = 28),
arcuate ligament (n = 20), popliteus tendon (n = 20), superior popliteomeniscal
fascicle (n = 18), lateral collateral ligament (n = 8), popliteofibular ligament
(n = 7), biceps tendon (n = 4), iliotibial band (n = 3), and fabellofibular
ligament (n = 1). Seventy-five percent of all patients with combined ACL and PLC
injuries had bone contusions involving the lateral compartment of the knee. The
presence of these contusions strongly correlated with superior popliteomeniscal
fascicle lesions (p < 0.05). There was no correlation between injuries to other
structures of the PLC and other intra-articular lesions. CONCLUSION: Missed
injuries of the PLC lead to considerable morbidity. The relevance of this study
is to highlight that these injuries occur more frequently than previously
described and that an appropriate index of suspicion, clinical examination, and
MRI are all required to reduce the risk of missed diagnoses. The results of this
study support previous suggestions that the rate of concomitant PLC injury in the
ACL-deficient knee is under-reported. The rate of combined injuries in this
series was 19.7%. The key message of this paper is that PLC injury is common in
the presence of ACL injury and should be sought both clinically and
radiologically.
PMID- 28424851
TI - Vascularized fibular medialization for reconstruction of the tibial defects
following tumour excision.
AB - PURPOSE: The purpose of this study was to evaluate the functional and oncologic
results of fibular medialization when used alone as a single-stage reconstructive
technique after wide excision of malignant tumours of the proximal, middle, or
distal tibia. METHODS: Between December 2010 and May 2015, 14 patients (six males
and eight females) with primary malignant tumours of the tibia (eight proximal,
four diaphyseal, two distal) were treated by wide excision. The mean age of the
patients at the time of surgery was 23.2 years (11-38). The fibula was mobilized
medially with its vascular pedicle to fill the defect and was fixed by a long
plate and screws bypassing the graft. The average size of the defects
reconstructed was 19.5 cm (18-22). Patients were evaluated functionally using the
Musculoskeletal Tumour Society (MSTS) scoring system. RESULTS: The mean follow-up
period was 31.3 months (range, 17-54). The average time for complete union was
7.6 months (range, 6-9). At final follow-up all patients had fully united grafts;
11 walked without aids. Chest metastases developed in one patient, superficial
wound infection in two patients and leg length discrepancy in four patients; one
case had LLD of more than 3 cm. The mean MSTS score was 23/30 points (76.5%). The
minimum score was 40% (12/30) and the maximum was 90% (27/30). CONCLUSIONS:
Ipsilateral pedicled vascularized fibular centralisation or medialization is a
durable reconstruction for tibial defects after wide excision of bone tumours
with an acceptable functional outcome. Stable osteosynthesis is the key to union.
PMID- 28424852
TI - Clinical application of bone morphogenetic proteins for bone healing: a
systematic review.
AB - PURPOSE: This paper documents the existing evidence on bone morphogenetic
proteins (BMPs) use for the treatment of bone fractures, non-union, and
osteonecrosis, through a review of the clinical literature, underlying potential
and limitations in terms of cost effectiveness and risk of complications.
METHODS: A systematic review was performed on the PubMed database using the
following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone
regeneration) including papers from 2000 to 2016. The search focused on clinical
trials dealing with BMPs application to favor bone regeneration in bone
fractures, non-union, and osteonecrosis, in English language, with level of
evidence I, II, III, and IV. Relevant data (type of study, number of patients,
BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were
extracted and analyzed. RESULTS: Forty-four articles met the inclusion criteria:
10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series,
and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures,
and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found
among RCTs and comparative papers: 11 reported positive results for BMPs
augmentation, 3 obtained no significant effects, and 2 showed negative results.
The only study comparing the two BMPs showed a better outcome with rhBMP-2 for
non-union treatment. CONCLUSION: Clinical evidence on BMPs use for the treatment
of fractures, non-union, and osteonecrosis is still controversial, with the few
available reports being mainly of low quality. While positive findings have been
described in many studies, mixed results are still present in the literature in
terms of efficacy and adverse events. The difficulties in drawing clear
conclusions are also due to the studies heterogeneity, mainly in terms of
different BMPs applied, with different concomitant treatments for each bone
pathology. Therefore, further research with well-designed studies is needed in
order to understand the real potential of this biological approach to favour bone
healing.
PMID- 28424853
TI - Long-term results of ankle arthrodesis in children and adolescents with
haemophilia.
AB - INTRODUCTION: Ankle arthrodesis in patients with haemophilia is a joint-non
preserving treatment option often resulting in substantial pain relief and
termination of haemarthrosis by osseous consolidating of the joint. However,
limited data are available regarding ankle arthrodesis in young patients. AIM:
The aim of this study was to evaluate the long-term clinical and radiographic
results with a minimum follow-up of ten years in children with haemophilia who
underwent ankle arthrodesis. METHODS: We retrospectively reviewed the results of
ankle fusions performed in young haemophiliacs in our department between 1980 and
2006. The Meary procedure was used for arthrodesis, performed on patients with
closed growth plates. Only one patient had no fixation, due to being only six
years old. The modified American Orthopaedic Foot & Ankle Society (AOFAS)
hindfoot score was calculated at last follow-up, and standard radiographic
evaluations were performed. RESULTS: A total of 22 ankles were analysed from 17
patients. The mean follow-up was 19.7 +/- 8 years. The mean age of the patients
was 15.5 (6-23) years at the time of index surgery. There were no intra-operative
or peri-operative complications related to ankle arthrodesis. The mean modified
AOFAS score at last follow-up was 83 +/- 10.5. Radiographic assessment
demonstrated solid osseous fusion at the arthrodesis site, with no axis
deformities. Two patients developed secondary subtalar arthrosis, treated by
subtalar arthrodesis six years after initial ankle arthrodesis in one case.
CONCLUSION: In our study, tibiotalar arthrodesis in young patients with
haemophilia resulted in good long-term functional outcome with a low surgery
related complication rate.
PMID- 28424854
TI - The effectiveness of narrative enhancement and cognitive therapy: a randomized
controlled study of a self-stigma intervention.
AB - PURPOSE: Stigma has been proposed to be one of the most serious obstacles to
successful treatment, rehabilitation and inclusion in society of people with
severe mental illness. An aspect of stigma which has been increasingly discussed
is self-stigma, which refers to the internalization of negative stereotypes among
people with severe mental illness. The aim of the present study was to
investigate the effectiveness of a group-based anti self-stigma intervention,
narrative enhancement and cognitive therapy (NECT) as an add-on to treatment as
usual, with regard to changes in self-stigma, self-esteem, and subjective quality
of life. METHOD: After screening for eligibility 106 participants were included
in a randomized controlled trial using a wait-list control group, of which 87
completed the study. Assessments were made at baseline, at termination of the
intervention, and at a 6-month follow-up (intervention group only). RESULTS: The
results showed that NECT was effective in reducing self-stigma and improving self
esteem compared to treatment as usual only. No differences were shown regarding
subjective quality of life. Changes shown in the intervention group at
termination of intervention were stable at the 6-month follow-up. A regression
analysis showed that there was a positive relationship between exposure to the
intervention and reduction of self-stigma. CONCLUSIONS: The conclusion of the
present study is that, using a sample size with adequate power, NECT seems to be
an effective intervention with regard to diminishing self-stigma and improving
self-esteem, and that these improvements were stable at a 6-month follow-up.
There was a distinct relationship between number of sessions attended and
improvements in self-stigma and self-esteem controlling for confounding factors.
This puts attention to the importance of creating a group climate which
facilitate and encourage participation through the various phases of the
intervention.
PMID- 28424855
TI - Analysis of multiple soybean phytonutrients by near-infrared reflectance
spectroscopy.
AB - Improvement of the nutritional quality of soybean is usually facilitated by a
vast range of soybean germplasm with enough information about their multiple
phytonutrients. In order to acquire this essential information from a huge number
of soybean samples, a rapid analytic method is urgently required. Here, a
nondestructive near-infrared reflectance spectroscopy (NIRS) method was developed
for rapid and accurate measurement of 25 nutritional components in soybean
simultaneously, including fatty acids palmitic acid, stearic acid, oleic acid,
linoleic acid, and linolenic acid, vitamin E (VE), alpha-VE, gamma-VE, delta-VE,
saponins, isoflavonoids, and flavonoids. Modified partial least squares
regression and first, second, third, and fourth derivative transformation was
applied for the model development. The 1 minus variance ratio (1-VR) value of the
optimal model can reach between the highest 0.95 and lowest 0.64. The predicted
values of phytonutrients in soybean using NIRS technology are comparable to those
obtained from using the traditional spectrum or chemical methods. A robust NIRS
can be adopted as a reliable method to evaluate complex plant constituents for
screening large-scale samples of soybean germplasm resources or genetic
populations for improvement of nutritional qualities. Graphical Abstract ?.
PMID- 28424856
TI - Homogenous assay for protein detection based on proximity DNA hybridization and
isothermal circular strand displacement amplification reaction.
AB - This work proposed a homogenous fluorescence assay for proteins, based on the
target-triggered proximity DNA hybridization in combination with strand
displacement amplification (SDA). It benefited from target-triggered proximity
DNA hybridization to specifically recognize the target and SDA making recycling
signal amplification. The system included a molecular beacon (MB), an extended
probe (EP), and an assistant probe (AP), which were not self-assembly in the
absence of target proteins, due to the short length of the designed complementary
sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP
are bound to the target proteins, which induced the occurrence of proximity
hybridization between MB, EP, and AP and followed by strand displacement
amplification. Through the primer extension, a tripartite complex of probes and
target was displaced and recycled to hybridize with another MB, and the more
opened MB enabled the detection signal to amplify. Under optimum conditions, it
was used for the detection of streptavidin and thrombin. Fluorescence intensity
was proportional to the concentration of streptavidin and thrombin in the range
of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method
has a good selectivity, in which the fluorescence intensity of thrombin was ~37
fold or even larger than that of the other proteins at the same concentration. It
is a new and simple method for SDA-involved target protein detection and
possesses a great potential for other protein detection in the future. Graphical
abstract A homogenous assay for protein detection is based on proximity DNA
hybridization and strand displacement amplification reaction.
PMID- 28424857
TI - Extraction of cell-free DNA from urine, using polylysine-coated silica particles.
AB - DNA analysis is used for a variety of purposes, including disease diagnosis and
DNA profiling; this involves extracting DNA from living organisms. In this study,
we prepared polycationic silica particles to extract DNA that has the negatively
charged phosphate backbone from solution. The coated particles were prepared by
mixing conventional silica gel particles and poly-Lys; these particles could
efficiently extract 1.3 MUg of cell-free DNA from 50 mL of (male) urine. It is
expected that these easily prepared particles (just a mixture of two commercially
available chemicals) can be used as a noninvasive diagnostic tool for genetic
disorders such as cancer, diabetes, and hypertension. Graphical abstract
Effective extraction method of cfDNA from urine was developed that used
commercially available silica gel particles and poly-Lys.
PMID- 28424858
TI - Electrochemical simulation of biotransformation reactions of citrinin and
dihydroergocristine compared to UV irradiation and Fenton-like reaction.
AB - Mycotoxins occur widely in foodstuffs and cause a variety of mold-related health
risks to humans and animals. Elucidation of the metabolic fate of mycotoxins and
the growing number of newly discovered mycotoxins have enhanced the demand for
fast and reliable simulation methods. The viability of electrochemistry coupled
with mass spectrometry (EC/ESI-MS), Fenton-like oxidation, and UV irradiation for
the simulation of oxidative phase I metabolism of the mycotoxins citrinin (CIT)
and dihydroergocristine (DHEC) was investigated. The specific reaction products
are compared with metabolites produced by human and rat liver microsomes in
vitro. Depending on the applied potential between 0 and 2000 mV vs. Pd/H2 by
using a flow-through cell, CIT and DHEC are oxidized to various products. Besides
dehydrogenation and dealkylation reactions, several hydroxylated DHEC and CIT
species are produced by EC and Fenton-like reaction, separated and analyzed by LC
MS/MS and ESI-HRMS. Compared to reaction products from performed microsomal
incubations, several mono- and dihydroxylated DHEC species were found to be
similar to the reaction products of EC, Fenton-like reaction, and UV-induced
oxidation. Consequentially, nonmicrosomal efficient and economic simulation
techniques can be useful in early-stage metabolic studies, even if one-to-one
simulation is not always feasible.
PMID- 28424859
TI - Investigation of carbon-based nanomaterials as sorbents for headspace in-tube
extraction of polycyclic aromatic hydrocarbons.
AB - Carbon-based nanomaterials (CNM) represent promising materials for the
application as sorbents in micro- and other extraction devices. In this work, we
investigate the applicability of five different CNM (multi-walled carbon
nanotubes (MWCNTs), fullerenes, carboxylic acid functionalized multi-walled
carbon nanotubes (MWCNTs-COOH), graphene platelets, and carbon nanohorns) for
their performance on PAH extraction from the aqueous phase by headspace in-tube
extraction (HS-ITEX). Optimal extraction parameters for HS-ITEX were determined
using a Box-Behnken experimental design. From the extraction yield response,
central point analysis, fullerenes showed the best extraction properties for the
eight selected headspace compatible PAHs (naphthalene, acenaphthylene,
acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, and pyrene).
Fullerenes were used for a further method validation including the linear range,
limit of detection, precision, as well as recovery. Finally, extraction yields
were compared to a commercial material (Tenax GR), demonstrating that fullerene
represents a better option as sorbent in ITEX for PAH analysis. Method detection
limits for the PAH on fullerene ranged from 10 to 300 ng L-1, with recoveries
between 45 and 103%.
PMID- 28424860
TI - Influence of tibial hybrid fixation on graft tension and stability in ACL double
bundle reconstruction.
AB - PURPOSE: Initial graft tension in anterior cruciate ligament (ACL) reconstruction
affects stability and tension loss at follow-up. This study investigated the
influence of hybrid tibial fixation in 3-tunnel double-bundle ACL reconstruction
on initial graft tension and tension change and stability under anterior and
combined rotatory loads. METHODS: Eleven fresh-frozen cadaveric knees were
reconstructed with an ACL double bundle using a 3-tunnel technique. Grafts were
tightened to 80 N in 60 degrees (AM bundle) and 15 degrees (PL bundle) of
flexion. Anterior tibial translation under 134 N of anterior shear load and
translation under combined rotatory and valgus loads (10 Nm valgus stress, 4 Nm
internal tibial torque) were determined at 0 degrees , 30 degrees , 60 degrees ,
and 90 degrees flexion. In addition, graft tension under continuous passive
motion was determined. Intact, ACL-resected and ACL-reconstructed joints with
either tibial extracortical graft fixation or extracortical plus supplemental
aperture graft fixation (hybrid fixation) were tested. RESULTS: Hybrid fixation
did not increase graft tension in either bundle during fixation or in motion
without additional load. AM-bundle tension increased (p < 0.05) at 0 degrees
under combined rotatory and valgus loads and at 30 degrees and 60 degrees under
both loading conditions without decreasing the anterior tibial translation. PL
bundle tension increased (p < 0.05) only at 90 degrees under combined rotatory
and valgus loads. CONCLUSIONS: Tibial hybrid fixation in 3-tunnel double-bundle
ACL reconstruction increases time-zero AM- and PL-bundle tensions under loading
conditions, generating greater construct stiffness. This could lead to a longer
preservation of ACL-graft stability in clinical follow-up before bony
incorporation.
PMID- 28424861
TI - S -ketamine compared to etomidate during electroconvulsive therapy in major
depression.
AB - Objective of the study was to compare two commonly used anesthetic drugs, S
ketamine and etomidate, regarding their influence on seizure characteristics,
safety aspects, and outcome of electroconvulsive therapy (ECT) in major
depression. Treatment data of 60 patients who underwent a total number of 13 ECTs
(median) because of the severe or treatment-resistant major depressive disorder
(DSM-IV) were analyzed. Etomidate, mean dosage (SD) = 0.25 (0.04) mg/kg, was used
for anesthesia in 29 participants; 31 patients received S-ketamine, mean dosage
(SD) = 0.96 (0.26) mg/kg. Right unilateral brief pulse ECTs were performed. The
number of ECTs was individually adjusted to clinical needs, mean (SD) = 13.0
(4.3). Seizure characteristics, adverse events, and the clinical global
impression (CGI) scores were compared between the both groups during ECT series.
In the S-ketamine group, a lower initial seizure threshold (p = 0.014),
stimulation charge (p < 0.001), higher postictal suppression (p < 0.001), EEG
ictal amplitude (p = 0.04), EEG coherence (p < 0.001) and maximum heart rate (p =
0.015) were measured. Etomidate was associated with more frequent abortive
seizures (p = 0.02) and restimulations (p = 0.01). The CGI scores, the number of
sessions within an ECT series, and the incidence of adverse events did not differ
between groups. Due to its lower initial seizure threshold, S-ketamine might hold
a potential to become a clinically favorable anesthetic agent during ECT.
However, the current findings should be interpreted with caution, and further
prospective randomized clinical trials are required. Also, specific adverse
effects profile of S-ketamine, especially with regard to the cardiovascular risk,
needs to be taken into account.
PMID- 28424862
TI - Laparoscopic management of choledochal cysts: is a keyhole view missing the big
picture?
AB - In recent years, numerous articles have promoted laparoscopic surgical treatment
of choledochal cysts in children. Most of these reports assert that laparoscopic
excision and biliary reconstruction are as safe as open surgery and achieve
equivalent or better results. However, these conclusions are based on
retrospective analyses with median follow-up periods that rarely exceed 5 years.
Closer scrutiny of the laparoscopic literature indicates that the optimum
procedure for treating type I and most type IVa choledochal cysts, namely radical
excision of the extrahepatic bile ducts and reconstruction by wide hilar
hepaticoenterostomy, preferably hepaticojejunostomy, is not being carried out in
most cases. Performing a less radical excision exposes patients to a greater long
term risk of a bilioenteric stricture and its complications and malignant change
in residual extrahepatic bile ducts. Currently, the long-term outcomes of surgery
for choledochal cysts are being eclipsed by the short-term gains of laparoscopic
techniques. The prime objective in the surgical management of choledochal cysts
is the long-term health of the patient; laparoscopic techniques are simply
another method of performing the surgery and they should not become the standard
of care unless long-term outcomes are similar to best practice open surgery.
PMID- 28424863
TI - Current practice regarding timing of patent processus vaginalis ligation for
idiopathic hydrocele in young boys: a survey of UK surgeons.
AB - PURPOSE: The aim of this study was to determine the current UK practice regarding
timing of surgical repair of hydroceles in young boys. METHODS: Through a
validated, online survey, participants were asked their preferred management
option in five different clinical scenarios across five age ranges. RESULTS: 71
responses were included in the analysis. The most common age to offer surgical
intervention for a congenital hydrocele that is stable or increasing in size, or
a hydrocele of the cord is 24-36 months. For a stable hydrocele presenting after
12 months of age, the most common age to offer repair is between 36 and 48
months. Approximately 1/4 of respondents defer surgery until 4 years of age for
any stable hydrocele. For a congenital hydrocele that is decreasing in size, the
majority of respondents (57%) do not offer surgical intervention even over 4
years of age. The majority of respondents (61%) do not differentiate between
communicating and non-communicating hydroceles when considering age for repair.
CONCLUSION: These results suggest that there is uncertainty regarding the optimum
age for PPV ligation and adequate underlying variability in practice to support a
prospective study of the optimum age for hydrocele repair and the natural history
of PPV closure.
PMID- 28424864
TI - Loss of chromosome Y (LOY) in blood cells is associated with increased risk for
disease and mortality in aging men.
AB - Recent discoveries have shown that harboring cells without the Y chromosome in
the peripheral blood is associated with increased risk for all-cause mortality
and disease such as different forms of cancer, Alzheimer's disease, as well as
other conditions in aging men. In the entire world, the life expectancy of men is
shorter compared to women, a sex difference that has been known for centuries,
but the underlying mechanism(s) are not well understood. As a male-specific
genetic risk factor, an increased risk for pathology and mortality associated
with mosaic loss of chromosome Y (LOY) in blood cells could help to explain that
men on average live shorter lives compared to women. This review primarily
focuses on observed associations between LOY in blood and various diseases in
aging men. Other topics covered are known risk factors for LOY, methods to detect
LOY, and a discussion regarding mechanisms such as immunosurveillance, that could
possibly explain how an acquired mutation in blood cells can be associated with
disease processes in other organs.
PMID- 28424865
TI - Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological
diagnosis of congenital and acquired isolated hypoganglionosis.
AB - Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two
subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the
rarity of the disease and the lack of defining histological criteria, the concept
of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens
from 79 patients diagnosed with Hirschsprung's disease (HD) (n = 49), CIHG (n =
25), and AIHG (n = 5) collected between January 1996 and December 2015.
Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin
and eosin staining and immunohistochemical staining using Hu C/D and CD56. We
evaluated (immuno)histopathological findings, counted the number of ganglion
cells, and measured the size of Auerbach's plexus. Hu C/D labeled neuronal cell
bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion
cells in Auerbach's plexus in the normoganglionic segment (NGS) were
immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were
replaced by CD56-positive extrinsic nerve fibers and bundles. The number of
ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p
< 0.05). Auerbach's plexus was significantly smaller in CIHG (p < 0.05) but in
AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56
is useful for definitive histopathological diagnosis of IHG.
PMID- 28424866
TI - Histopathological findings of extra-ileal manifestations at initial diagnosis of
Crohn's disease-related ileitis.
PMID- 28424867
TI - J-shaped relationship between habitual coffee consumption and 10-year (2002-2012)
cardiovascular disease incidence: the ATTICA study.
AB - PURPOSE: The purpose of this work was to evaluate the association between coffee
consumption and 10-year cardiovascular disease (CVD) incidence in the ATTICA
study, and whether this is modified by the presence or absence of metabolic
syndrome (MetS) at baseline. METHODS: During 2001-2002, 3042 healthy adults (1514
men and 1528 women) living in the greater area of Athens were voluntarily
recruited to the ATTICA study. In 2011-2012, the 10-year follow-up was performed
in 2583 participants (15% of the participants were lost to follow-up). Coffee
consumption was assessed by a validated food-frequency questionnaire at baseline
(abstention, low, moderate, heavy). Incidence of fatal or non-fatal CVD event was
recorded using WHO-ICD-10 criteria and MetS was defined by the National
Cholesterol Education Program Adult Treatment panel III (revised) criteria.
RESULTS: Overall, after controlling for potential CVD risk factors, the
multivariate analysis revealed a J-shaped association between daily coffee
drinking and the risk for a first CVD event in a 10-year period. Particularly,
the odds ratio for low (<150 ml/day), moderate (150-250 ml/day) and heavy coffee
consumption (>250 ml/day), compared to abstention, were 0.44 (95% CI 0.29-0.68),
0.49 (95% CI 0.27-0.92) and 2.48 (95% CI 1.56-1.93), respectively. This inverse
association was also verified among participants without MetS at baseline, but
not among participants with the MetS. CONCLUSIONS: These data support the
protective effect of drinking moderate quantities of coffee (equivalent to
approximately 1-2 cups daily) against CVD incidents. This protective effect was
only significant for participants without MetS at baseline.
PMID- 28424868
TI - Non-invasive measurements of the dynamic changes in the ciliary muscle,
crystalline lens morphology, and anterior chamber during accommodation with a
high-resolution OCT.
AB - PURPOSE: The purpose of the study was to assess non-invasively the changes in the
anterior chamber eye, crystalline lens morphology, and ciliary muscle during
accommodation by means of an anterior chamber optical coherence tomographer
(OCT), and correlate them with vergence. METHODS: Twenty-five eyes of twenty-five
healthy subjects, whose mean age was 29.9+/-7.1 years, were included and measured
with an anterior chamber OCT. The central corneal thickness (CCT), anterior
chamber depth (ACD), anterior crystalline lens radius of curvature (ALRC),
crystalline lens thickness (CLT), and ciliary muscle area (CMA) were measured for
each participant at 0, -1, -2, and -3 D of target vergence. A linear model was
used to assess the correlation of each eye parameter with the vergence demand.
RESULTS: The mean CCT showed no change for all the accommodative stimuli. The
mean ACD and ALRC decreased with the vergence, about 4.5 and 30 % at -3 D,
respectively. On the contrary, the CLT and CMA showed an opposite tendency, where
the mean CLT was increased by 4.0 % and the mean CMA was done by 26% at -3 D.
Statistical significant differences (p < 0.001) were obtained among all vergences
for each eye metric, except for the CCT (p = 0.76). CONCLUSION: The ACD and ALRC
decreased about 2 and 10 % per dioptre of accommodation, respectively; whereas
the CLT and CMA increased about 2 and 9 %, respectively. These results add
knowledge regarding the understanding of accommodation and give new perspectives
for biomechanics and biometry.
PMID- 28424869
TI - Review on diagnosis and management of urolithiasis in pregnancy: an ESUT
practical guide for urologists.
AB - PURPOSE: Management of urolithiasis in pregnancy can be challenging for most
urologists with diagnostic and treatment dilemma to ensure the best outcome for
both mother and fetus. We wanted to review the literature for urolithiasis in
pregnancy with a practical management guide for urologists. METHODS: A non
systematic review of literature was carried out for all English language
literature using Medline. To ensure a more comprehensive search, the review of
diagnosis and management of pregnant patients with urolithiasis was carried out
separately, by two authors independently. Due to diagnostic complexity,
investigations (US, CT, MRI) carried out were assessed separately. RESULTS: Our
search included diagnostic studies such as US, CT and MRI (73, 20 and 27
articles, respectively) and management studies (55 articles in total). Details on
etiology, radiation risk, safety of various diagnostic modalities, medications
and treatment options are covered through an evidence-based approach. We provide
a practical guide for urologists in what is clearly a stressful situation for
patient and physician alike. CONCLUSIONS: Urolithiasis in pregnancy needs a
careful multidisciplinary management to achieve good outcomes for both mother and
baby. Our review shows that a balanced approach for diagnosis and treatment seems
to achieve the best outcomes in pregnancy.
PMID- 28424870
TI - High intensity interval training does not impair strength gains in response to
resistance training in premenopausal women.
AB - PURPOSE: To compare the increases in upper- and lower-body muscle strength in
premenopausal women performing resistance training (RT) alone or alongside
concurrent high-intensity interval training (CT). METHODS: Sixteen women (26-40
years) were randomly assigned into two groups that performed either RT or CT.
Both groups performed the same RT program; however, CT performed additional high
intensity interval training (HIIT) on a bicycle ergometer before RT. The study
lasted 8 weeks and the participants were tested for ten repetition maximum (10RM)
load in elbow flexion (barbell biceps curl) and knee extension exercises pre- and
post-intervention. RT was performed with 10-12 repetitions to self-determined
repetition maximum in the first four weeks and then progressed to 8-10. During
CT, HIIT was performed before RT with six 1-min bouts at 7-8 of perceived
subjective exertion (RPE) and then progressed to eight bouts at 9-10 RPE.
RESULTS: Analysis of variance revealed significant increases in upper and lower
body strength for both the RT and CT groups. Biceps barbell curl 10RM load
increased from 12.9 +/- 3.2 kg to 14 +/- 1.5 kg in CT (p < 0.05) and from 13 +/-
1.8 kg to 15.9 +/- 2.5 kg in RT (p < 0.05), with no significant between-groups
differences. Knee extension 10RM increase from 31.9 +/- 11.6 kg to 37.5 +/- 8.5
kg for CT (p < 0.05) and from 30.6 +/- 8.6 kg to 41.2 +/- 7.4 kg for RT (p <
0.05). CONCLUSION: In conclusion, performing HIIT on a cycle ergometer before
resistance training does not seem to impair muscle strength increases in the knee
extensors or elbow flexors of pre-menopausal women. This information should be
considered when prescribing exercise sessions, since both activities may be
combined without negative effects in muscle strength.
PMID- 28424872
TI - Percutaneous endoscopic sigmoidopexy using T-fasteners for management of sigmoid
volvulus.
AB - BACKGROUND: Sigmoid volvulus (SV) is the third leading cause of large bowel
obstruction after colonic neoplasms and diverticular disease. SV has
traditionally been managed via endoscopic detorsion and decompression followed by
non-emergent surgical resection owing to the high risk of recurrence. Most cases
of SV occur in elderly debilitated patients with multiple comorbidities and may
not be candidates for surgical resection. Endoscopic sigmoidopexy has been
described as an alternative to surgical resection. Here, we describe our
experience with endoscopic sigmoidopexy using T-fasteners. METHODS: Three
patients with recurrent SV that were identified as poor surgical candidates by
our colorectal surgery team underwent endoscopic sigmoidopexy. The patients
received preoperative bowel preparation. A colonoscope was inserted and the site
of the volvulus was visualized and assessed for adequate decompression.
Subsequently, four points of fixation were identified and T-fasteners were
deployed. RESULTS: Two patients underwent successful sigmoidopexy without any
complications or recurrence on follow-up. One patient developed post procedure
pneumoperitoneum that was successfully treated conservatively; however, he passed
away from their underlying comorbidities. CONCLUSION: Overall, preliminary
results for sigmoidopexy using T-fasteners have been promising, offering a
potential option to prevent recurrence in high risk patients unsuitable for
surgical intervention.
PMID- 28424871
TI - Final analysis of the randomised PEAK trial: overall survival and tumour
responses during first-line treatment with mFOLFOX6 plus either panitumumab or
bevacizumab in patients with metastatic colorectal carcinoma.
AB - PURPOSE: To report planned final overall (OS) and progression-free survival (PFS)
analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with
previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer
(mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary
endpoint was PFS; secondary endpoints included OS, objective response rate,
duration of response (DoR), time to response, resection and safety. Treatment
effect by tumour RAS status was a prespecified objective. Exploratory analyses
included early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: One
hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS
was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months;
hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029)
and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p =
0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab
was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3
versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and
RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR =
0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were
improved in the panitumumab group. More panitumumab patients experienced >=30%
ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No
new safety signals occurred. CONCLUSIONS: First-line panitumumab + mFOLFOX6
increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.
PMID- 28424873
TI - The changes in the reproductive barrier between hexaploid wheat (Triticum
aestivum L.) and rye (Secale cereale L.): different states lead to different
fates.
AB - MAIN CONCLUSION: The changes in the reproductive barrier between hexaploid wheat
( Triticum aestivum L.) and rye ( Secale cereale L.) can be induced using in situ
embryo rescue of abnormal embryos, yielding stable fertile amphidiploid plants.
In intergeneric crosses between hexaploid wheat (Triticum aestivum L.) and rye
(Secale cereale L.), postzygotic barriers may occur at different stages of hybrid
development. One such mechanism is embryo lethality, which is genetically
determined by the interaction and expression of two incompatible genes in wheat
(Eml-A1) and rye (Eml-R1). Using in vitro culture methods as stressors, we
overcame this hybrid lethality. Normal and abnormal embryos were observed to
build embryogenic calli and produce regenerated plantlets in a similar manner.
The high regenerative capacity of the abnormal embryos led us to conclude that
the reproductive barrier in these intergeneric hybrids may have an epigenetic
origin that can be easily overcome by culturing immature embryos via callus
induction. After colchicine treatment during callus culture, amphidiploid plants
were obtained. However, most of these plants did not produce seeds, due mainly to
sterility of the pollen but also of the embryo sacs. These findings demonstrate
that hybrid sterility affects both male and female gametophytes in plants
obtained from abnormal embryos. The key roles of double fertilization and stress
factors in the implementation of the apical meristem formation program in embryos
from incompatible intergeneric crosses between hexaploid wheat and rye during in
vitro culture are discussed. We also propose a hypothetical model for a wheat-rye
lethality system involving differential expression of incompatible wheat Eml-A1
and rye Eml-R1b alleles in an identical genetic background.
PMID- 28424875
TI - Erratum to: Neuropsychological improvement after posterior fossa arachnoid cyst
drainage.
PMID- 28424874
TI - Identification of OsMYC2-regulated senescence-associated genes in rice.
AB - MAIN CONCLUSION: The jasmonic acid (JA)-responsive transcription factor OsMYC2
acts as a positive regulator of leaf senescence by direct regulation of some
senescence-associated genes in rice. OsMYC2, a transcription factor (TF), acts as
a positive regulator of jasmonic acid (JA) signaling involved in development and
defense in rice. Here, we report that OsMYC2 plays an important role in leaf
senescence under dark-induced senescence (DIS) conditions. Overexpression of
OsMYC2 significantly promoted leaf senescence, indicated by reduction of
chlorophyll content under DIS conditions in rice. Leaf senescence under the DIS
conditions was negatively regulated by OsJAZ8, a rice jasmonate ZIM-domain
protein involved in the JA signaling pathway. OsMYC2 upregulated the expression
of some senescence-associated genes (SAGs) and selectively bound to the G-box/G
box-like motifs in the promoters of some SAGs in vivo. These results suggest that
OsMYC2 acts as a positive regulator of leaf senescence by direct- or indirect
regulation of SAGs in rice.
PMID- 28424876
TI - Extent of surgical resection and adjuvant temozolomide improves survival in
pediatric GBM: a single center experience.
AB - BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance
of concurrent and adjuvant temozolomide is not known in this subset of patients.
METHODS: We retrospectively analyzed our database between 2000 and 2015. All
patients were treated with maximally safe surgical resection. This was followed
by a uniform treatment schedule of post-operative radiation with concurrent daily
temozolomide at 75 mg/m2. Radiation dose was 60 Gy in 30 fractions planned by 3
dimensional conformal radiotherapy. Concurrent and adjuvant temozolomide was used
in all patients treated after 2007. Four weeks later, adjuvant temozolomide was
started at 150 mg/m2, day 1 to 5 every 28 days and escalated to 200 mg/m2 from
the second cycle onwards if well tolerated. Log-rank test was used to compare
survival distribution. The data was analyzed using SPSS (version 16). RESULTS:
Fifty-one patients were analyzed. Median age was 14 years (range: 5 to 21 years).
Thirty-five males and 16 females were noted. Median symptom duration was 4
months. Twenty-eight patients underwent a gross total resection (GTR) while 17
underwent a subtotal resection; six patients underwent decompression. Thirty
three patients received concurrent chemotherapy while 27 received adjuvant
chemotherapy. Median progression-free survival (PFS) was 15.1 months. One- and 3
year PFS was 54.4% and 3-year PFS was 24.6.7%. The median overall survival was
17.4 months. In univariate analysis survival was better for gross total resection
(17.4 months vs. 11.5 months; p = 0.037), and significance maintained after
multivariate analysis p = 0.026, HR 3.069, 95% CI 1.14-8.23. In univariate
analysis, survival was better for patients receiving temozolomide but did not
achieve significance. However, in multivariate analysis, use of temozolomide was
associated with significantly improved survival p = 0.036, HR 3.315, 95% CI 1.07
10.19. CONCLUSIONS: GTR improves survival significantly in pGBM. Adjuvant
temozolomide may improve survival in pGBM.
PMID- 28424877
TI - [Fuchs uveitis].
AB - Fuchs uveitis (FU) is a frequent, chronic course of intraocular inflammation,
which is associated with a gradual onset of decreased visual acuity. The clinical
manifestation of the triad of heterochromia, cataract and glaucoma varies
considerably. This explains the often delayed diagnosis. Although the aetiology
and pathogenesis of the changes are still unclear, there is no doubt that
infections play a significant role. Intraocular antibodies directed against
rubella viruses show a high association with the disease pattern, and their
detection can even be used to support the diagnosis. The treatment of FU is
limited to symptomatic measures. Corticosteroids are usually only moderately
effective and should be used with caution due to adverse effects, with
progression of cataract and secondary glaucoma. The prognosis of the disease can
be regarded as favourable and depends essentially on the secondary changes.
PMID- 28424878
TI - Oral health in patients with renal disease: a longitudinal study from predialysis
to kidney transplantation.
AB - OBJECTIVES: The aim of this longitudinal study was to compare the oral health of
chronic kidney disease patients at the predialysis (baseline) and post
transplantation (follow-up) stages and to investigate differences in oral health
between diabetic nephropathy and other kidney disease patients at follow-up.
MATERIALS AND METHODS: Fifty-three kidney disease patients (34 men) aged 31-86
years were followed up to 157 months. Clinical and radiological oral
examinations, salivary and laboratory analyses, and oral health behavior
questionnaires were conducted at the predialysis and follow-up stages at Helsinki
University Hospital, Finland. Oral inflammatory burden was estimated by
calculating deep periodontal pockets, periodontal inflammatory burden (PIBI),
decayed, missing, and filled teeth (DMFT), and total dental indices (TDI).
Results were analyzed using cross-tabulation Pearson chi-square or Fisher's exact
test and the Mann-Whitney U test, and the McNemar and Wilcoxon signed-rank test.
RESULTS: At the predialysis stage, patients more often had calculus and deep
periodontal pockets; TDI, PIBI, number of teeth, and salivary flow rates were
also statistically significantly higher compared to follow-up. At follow-up,
diabetic nephropathy patients more often had Candida growth, more plaque, and
used more drugs and had lower stimulated salivary flow than patients with other
kidney diseases. CONCLUSION: Oral health was better at follow-up than at the
predialysis stage; however, attention should be given to the lower salivary flow
rate and higher number of drugs used at that stage. CLINICAL RELEVANCE: This
study confirms the importance of treating oral infectious foci at the predialysis
stage in order to prevent adverse outcomes after kidney transplantation.
PMID- 28424879
TI - Drinking Water Management and Governance in Canada: An Innovative Plan-Do-Check
Act (PDCA) Framework for a Safe Drinking Water Supply.
AB - Drinking water management in Canada is complex, with a decentralized, three
tiered governance structure responsible for safe drinking water throughout the
country. The current approach has been described as fragmented, leading to
governance gaps, duplication of efforts, and an absence of accountability and
enforcement. Although there have been no major waterborne disease outbreaks in
Canada since 2001, a lack of performance improvement, especially in small
drinking water systems, is evident. The World Health Organization water safety
plan approach for drinking water management represents an alternative
preventative management framework to the current conventional, reactive drinking
water management strategies. This approach has seen successful implementation
throughout the world and has the potential to address many of the issues with
drinking water management in Canada. This paper presents a review and strengths
weaknesses-opportunities-threats analysis of drinking water management and
governance in Canada at the federal, provincial/territorial, and municipal
levels. Based on this analysis, a modified water safety plan (defined as the plan
do-check-act (PDCA)-WSP framework) is proposed, established from water safety
plan recommendations and the principles of PDCA for continuous performance
improvement. This proposed framework is designed to strengthen current drinking
water management in Canada and is designed to fit within and incorporate the
existing governance structure.
PMID- 28424880
TI - Herbicide Toxicity Testing with Non-Target Boreal Plants: The Sensitivity of
Achillea millefolium L. and Chamerion angustifolium L. to Triclopyr and Imazapyr.
AB - Terrestrial plant toxicity tests were conducted to determine the sensitivity of
two boreal plants, yarrow (Achillea millefolium L.) and fireweed (Chamerion
angustifolium L.), to the herbicides imazapyr and triclopyr. Both plants are
common non-target species on northern powerline rights-of-way where the impacts
of proposed herbicide applications are of concern. In the vegetative vigour test,
triclopyr foliar spray caused extensive damage to A. millefolium at <50% of the
maximum field application rate (inhibition concentration (IC)50 = 1443.8 g a.i.
ha-1) and was lethal to C. angustifolium at the lowest dose tested (1210.9 g a.i.
ha-1). Both species demonstrated extremely high sensitivity to imazapyr foliar
spray: IC50s = 8.29 g a.i. ha-1 and 4.82 g a.i. ha-1 (<1.5% of the maximum field
rate). The seedling emergence and seedling growth tests were conducted in the
organic horizon of five boreal soils. Few differences in herbicide
bioavailability between soils were detected. Triclopyr limited growth of A.
millefolium, C. angustifolium and standard test species Calamagrostis canadensis
at low levels (most IC50 estimates between 2-20 ug g-1). For imazapyr, IC50
estimates could not be calculated as there was >75% inhibition of endpoints at
the lowest doses of ~2 ug g-1. A foliar application of triclopyr or imazapyr for
woody species control would likely cause significant damage to boreal non-target
plants. The high sensitivity of both species to herbicide residues in soil
indicates long term impacts are dependent on herbicide degradation rates in
northern conditions. A. millefolium performed well and is recommended for use in
toxicity testing relevant to boreal regions.
PMID- 28424881
TI - Screening of commercial enzymes for poly(ethylene terephthalate) (PET) hydrolysis
and synergy studies on different substrate sources.
AB - Poly(ethylene terephthalate) (PET) is one of the most consumed plastics in the
world. The development of efficient technologies for its depolymerization for
monomers reuse is highly encouraged, since current recycling rates are still very
low. In this study, 16 commercial lipases and cutinases were evaluated for their
abilities to catalyze the hydrolysis of two PET samples. Humicola insolens
cutinase showed the best performance and was then used in reactions on other PET
sources, solely or in combination with the efficient mono(hydroxyethyl
terephthalate)-converting lipase from Candida antarctica. Synergy degrees of the
final titers of up to 2.2 (i.e., more than double of the concentration when both
enzymes were used, as compared to their use alone) were found, with increased
terephthalic acid formation rates, reaching a maximum of 59,989 umol/L (9.36
g/L). These findings open up new possibilities for the conversion of post
consumer PET packages into their minimal monomers, which can be used as drop in
at existing industrial facilities.
PMID- 28424882
TI - Effectiveness of dry needling and high-volume image-guided injection in the
management of chronic mid-portion Achilles tendinopathy in adult population: a
literature review.
AB - Achilles tendinopathy is a common overuse condition affecting the adult
population. The incidence is on the rise because of greater participation of
people in recreational or competitive sporting activities. There are several
treatment options available both non-operative and operative. Ultrasound-guided
dry needling and high-volume image-guided injection is relatively a new
procedure. The aim of this study was to find out the effectiveness of dry
needling and HVIGI in the management of mid-portion chronic Achilles tendinopathy
by performing a literature review. Search strategy was devised to find the
suitable articles for critical appraisal using the electronic databases. Four
articles were selected for critical appraisal, and these papers showed good short
to long-term results of image-guided high-volume injection in the management of
Achilles tendinopathy. We conclude that high-volume image-guided injection is
effective in the management of Achilles tendinopathy. It provides good short- and
medium-term relief of symptoms. It should be considered as one of the many
options available for this condition.
PMID- 28424883
TI - Acute basophilic leukemia with add(3)(q12) accompanied by histamine excess
symptoms.
PMID- 28424884
TI - Principle and basic property of the sequential flow pump.
AB - In the emergency care field, early treatment of acute heart or respiratory
failure has been a global concern. In severe cases, patients are frequently
required to be on an extracorporeal membrane oxygenator (ECMO) life support. To
make the ECMO system more compact and portable, we proposed a sequential flow
type centrifugal pump named the sequential flow pump (SFP). In this study,
principle and basic properties of this novel blood pump were examined by
computational fluid dynamic (CFD) analysis and an experimental model. In the SFP,
fluid is given centrifugal force sequentially twice with a single closed
impeller. This sequential pressurization mechanism enables high-pressure output
without high impeller speed. To realize easy integration of a blood pump with an
artificial lung, the inlet and outlet ports are located at lateral side and
center of the pump, respectively, which is the reverse configuration of
conventional centrifugal pumps. The computational model was composed for CFD
analysis and the experimental model was developed for the experiment of the
actual pump. For both models, dimension of the impeller and volute was designed
to be equal. In the CFD analysis, the SFP could generate higher performance than
the single pressurization model with the same rotational speed of the impeller.
Basic property of the experimental model was very similar to that of the
computational model. The results showed the possibility that the SFP would be
more suitable for the compact ECMO system than conventional centrifugal pumps.
PMID- 28424885
TI - Bedside repositioning of a dislocated Avalon-cannula in a running veno-venous
ECMO.
AB - We report a repositioning maneuver of a dislocated Avalon Elite dual lumen
catheter during ongoing veno-venous ECMO support. The inferior tip of the
catheter dislocated into a liver vein, which was accompanied by a dramatic
decrease in pump flow. After standard repositioning maneuvers under transthoracic
echocardiographic guidance had failed, a special guiding sheath was inserted into
the main lumen through a Y-connector with a valve. Over this valve, a stiff wire
could be placed into the inferior vena cava to help guiding the catheter back
into the correct position.
PMID- 28424886
TI - Detection of koi herpesvirus (KHV) using a monoclonal antibody against Cyprinus
carpio IgM.
AB - Koi herpesvirus disease (KHVD) is associated with high mortality in both common
carp and koi carp (Cyprinus carpio L.) worldwide. The indirect detection of fish
viruses based on the identification of antibodies has emerged as a practical and
reliable means of diagnosis. Thus, it is important to create monoclonal
antibodies (MAbs) against carp IgM. By using hybridoma-monoclonal antibody
technology, one hybridoma cell line secreting MAbs against IgM from carp was
established. In western blot analysis, the secreted MAb from cell line A5-E10
recognized the heavy chain of IgM from common carp or koi but did not react with
immunoglobulins from three different fish species: grass carp (Ctenopharyngodon
idella), tilapia (Oreochromis mossambicus) and Mandarin fish (Siniperca chuatsi).
These results demonstrated that this MAb is highly specific for the IgM of carp
and suggested that it can be used for monitoring the immunity level of carp, for
example for indirect KHV diagnosis by antibody ELISA. We therefore established an
indirect ELISA, which was tested using 200 serum samples from koi from three
farms. The final results showed that 147 (73.5%) samples were confirmed to be KHV
antibody negative and 53 (26.5%) were definitely positive, containing antibodies
against KHV.
PMID- 28424887
TI - A metagenomics study for the identification of respiratory viruses in mixed
clinical specimens: an application of the iterative mapping approach.
AB - Metagenomic approaches to detect viral genomes and variants in clinical samples
have various challenges, including low viral titers and bacterial and human
genome contamination. To address these limitations, we examined a next-generation
sequencing (NGS) and iterative mapping approach for virus detection in clinical
samples. We analyzed 40 clinical specimens from hospitalized children diagnosed
with acute bronchiolitis, croup, or respiratory tract infections in which virus
identification by viral culture or polymerase chain reaction (PCR) was
unsuccessful. For our NGS data analysis pipeline, clinical samples were pooled
into two NGS groups to reduce sequencing costs, and the depth and coverage of
assembled contigs were effectively increased using an iterative mapping approach.
PCR was individually performed for each specimen according to the NGS-predicted
viral type. We successfully detected previously unidentified respiratory viruses
in 26 of 40 specimens using our proposed NGS pipeline. Two dominant populations
within the detected viruses were human rhinoviruses (HRVs; n = 14) and human
coronavirus NL63 (n = 8), followed by human parainfluenza virus (HPIV), human
parechovirus, influenza A virus, respiratory syncytial virus (RSV), and human
metapneumovirus. This is the first study reporting the complete genome sequences
of HRV-A101, HRV-C3, HPIV-4a, and RSV, as well as an analysis of their genetic
variants, in Taiwan. These results demonstrate that this NGS pipeline allows to
detect viruses which were not identified by routine diagnostic assays, directly
from clinical samples.
PMID- 28424888
TI - Posttraumatic growth and well-being among adolescents and young adults (AYAs)
with cancer: a longitudinal study.
AB - PURPOSE: This study examines posttraumatic growth (PTG) among adolescents and
young adults (AYAs) with cancer, as well as its correlates and trajectories over
time. The study also explores the buffering role of PTG on the associations
between posttraumatic stress (PTS), health-related quality of life (HRQoL), and
psychological distress. METHODS: A multicenter, longitudinal, prospective study
was conducted among AYA cancer patients aged 14-39 years. One hundred sixty-nine
patients completed a self-report measure of PTG (PTGI) and PTS (PDS) 6, 12, and
24 months after baseline (within the first 4 months of diagnosis). At 24-month
follow-up, HRQoL (SF-36) and psychological distress (BSI-18) were also assessed.
RESULTS: Among participants, 14% showed increasing PTG, 45% remained at a stable
high PTG level, 14% showed decreasing PTG, and 27% remained at a stable low PTG
level. AYAs who remained high on PTG were more often younger, female, and
received chemotherapy. PTG level at 6-month follow-up was predictive of mental
HRQoL (beta = 0.19; p = 0.026) and psychological distress (beta = -0.14; p =
0.043) at 24-month follow-up when corrected for PTS and sociodemographic and
clinical covariates. No relationship between PTG and physical HRQoL was found.
The interactive effects of PTS and PTG on outcomes were not significant,
indicating that buffering did not take place. CONCLUSION: This study indicates
that PTG is dynamic and predicts mental well-being outcomes but does not buffer
the effects of PTS. Psychosocial interventions should focus on promoting PTG and
reducing PTS in order to promote the adjustment of AYAs diagnosed with cancer.
PMID- 28424889
TI - Quality of life with biweekly docetaxel and capecitabine in advanced gastro
oesophageal cancer.
AB - PURPOSE: This study aimed to evaluate the feasibility and tolerability of
biweekly docetaxel with capecitabine as first-line treatment in advanced gastro
oesophageal cancer. METHODS: Fifty-three patients at median age of 61 years with
advanced gastric cancer were included in this prospective, non-randomized,
multicentre phase II trial to receive intravenous docetaxel 50 mg/m2 on days 1
and 15, and oral capecitabine 1250 mg/m2 every 12 h, on days 1-7 and 15-21 of
each 28-day cycle. QOL was assessed using EORTC QLQ-C30, together with the
gastric module (QLQ-STO 22). RESULTS: Forty-six patients were evaluable for QOL
analyses. No deterioration in global health status was found. Social functioning
scores improved, and eating difficulties and pain were alleviated during
treatment. The most common grade 3 or 4 toxicity was neutropenia (47%), whereas
neutropenic fever was uncommon (6%). The clinical benefit rate was 60%, including
complete and partial responses as well as stabilized disease. Median overall
survival was 8.8 months (95% CI 5.8-11.9 months), and median time to progression
was 6.2 months (95% CI 4.9-7.5 months). CONCLUSIONS: Biweekly docetaxel with
capecitabine is a feasible treatment in AGC, delivered on an outpatient basis,
with no need for central venous access device. No deterioration of global health
status was reported. In addition, pain and eating difficulties were alleviated
during study treatment. This trial is registered at ClinicalTrials.gov , number
NCT00669370.
PMID- 28424890
TI - Left atrial electromechanical conduction time predicts atrial fibrillation in
patients with mitral stenosis: a 5-year follow-up speckle-tracking
echocardiography study.
AB - Prolonged left atrial electromechanical conduction time is related with atrial
electrical remodeling, and is predictive of the development of atrial
fibrillation. The aim of our study was to examine whether left atrial
electromechanical conduction time (EMT) and left atrial strain as measured by
speckle tracking echocardiography (STE) are predictors for the development of
atrial fibrillation (AF) in patients with mitral stenosis (MS) at 5-year follow
up. A total of 81 patients (61% females; mean age 38.1 +/- 12.1 years) with mild
or moderate MS of rheumatic origin according to ACC/AHA guidelines who were in
sinus rhythm, and were asymptomatic or have NYHA class 1 symptom were included in
the study. AF was searched by 12-lead electrocardiograms or 24-h Holter
recordings during follow-up period. Atrial electromechanical conduction time
(EMT), peak atrial longitudinal strain (PALS) and peak atrial contraction strain
(PACS) were measured by STE. EMTs was defined as the interval between the onset
of P-wave to the peak late diastolic longitudinal strain in the basal lateral and
septal wall. During the follow-up period of 5 years (mean follow-up duration,
48.2 +/- 13.3 months), 30 patients (37%) developed AF on standard 12-lead ECG or
at their 24-h Holter recording. At follow-up, patients who developed AF were
older than patients without AF (42.4 +/- 11.3 vs. 35.6 +/- 11.9, p = 0.014).
Mitral valve area (MVA) (1.39 +/- 0.14 vs. 1.48 +/- 0.18, p = 0.03), PALS (13.4
+/- 4.6 vs. 19 +/- 5.2, p < 0.001) and PACS (6 +/- 2.7 vs. 8.4 +/- 3.8, p =
0.004), were lower in patients who developed AF than in patients who did not
develop. However, EMTs-Septal (208.2 +/- 28.4 vs. 180.2 +/- 38, p = 0.001), and
EMTs-Lateral (247.1 +/- 27.6 vs. 213.3 +/- 43.5, p < 0.001) were longer in
patients with AF than in patients without. In multivariate Cox regression
analysis, PALS and left atrial EMTs-Lateral were independent predictors for
development of AF at follow-up. In patients with mitral stenosis, left atrial
strain and electromechanical conduction time in the lateral wall during the long
term follow-up period are predictive for the development of atrial fibrillation.
Speckle tracking echocardiography is a basic and easily-implemented method based
on left atrial parameters which may be helpful for early detection of atrial
fibrillation in patients with mitral stenosis.
PMID- 28424892
TI - Bayesian characterization of uncertainty in species interaction strengths.
AB - Considerable effort has been devoted to the estimation of species interaction
strengths. This effort has focused primarily on statistical significance testing
and obtaining point estimates of parameters that contribute to interaction
strength magnitudes, leaving the characterization of uncertainty associated with
those estimates unconsidered. We consider a means of characterizing the
uncertainty of a generalist predator's interaction strengths by formulating an
observational method for estimating a predator's prey-specific per capita attack
rates as a Bayesian statistical model. This formulation permits the explicit
incorporation of multiple sources of uncertainty. A key insight is the
informative nature of several so-called non-informative priors that have been
used in modeling the sparse data typical of predator feeding surveys. We
introduce to ecology a new neutral prior and provide evidence for its superior
performance. We use a case study to consider the attack rates in a New Zealand
intertidal whelk predator, and we illustrate not only that Bayesian point
estimates can be made to correspond with those obtained by frequentist
approaches, but also that estimation uncertainty as described by 95% intervals is
more useful and biologically realistic using the Bayesian method. In particular,
unlike in bootstrap confidence intervals, the lower bounds of the Bayesian
posterior intervals for attack rates do not include zero when a predator-prey
interaction is in fact observed. We conclude that the Bayesian framework provides
a straightforward, probabilistic characterization of interaction strength
uncertainty, enabling future considerations of both the deterministic and
stochastic drivers of interaction strength and their impact on food webs.
PMID- 28424891
TI - A phase I dose-escalation study of Selumetinib in combination with Erlotinib or
Temsirolimus in patients with advanced solid tumors.
AB - : Background Combinations of molecularly targeted agents may provide optimal anti
tumor activity and improve clinical outcomes for patients with advanced cancers.
Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective,
allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which
is constitutively activated in many cancers. We investigated the safety,
tolerability, and pharmacokinetics (PK) of selumetinib in combination with
molecularly targeted drugs erlotinib or temsirolimus in patients with advanced
solid tumors. Methods Two-part study: dose escalation, to determine the maximum
tolerated dose (MTD) of selumetinib in combination with erlotinib 100 mg once
daily (QD) or temsirolimus 25 mg once weekly, followed by dose expansion at the
respective combination MTDs to further investigate safety and anti-tumor effects.
Results 48 patients received selumetinib plus erlotinib and 32 patients received
selumetinib plus temsirolimus. The MTD with erlotinib 100 mg QD was selumetinib
100 mg QD, with diarrhea being dose limiting. The most common all grade adverse
events (AEs): diarrhea, rash, nausea, and fatigue. Four (8.3%) patients had >=12
weeks stable disease. The MTD with temsirolimus 25 mg once weekly was selumetinib
50 mg twice daily (BID), with mucositis and neutropenia being dose limiting. The
most commonly reported AEs: nausea, fatigue, diarrhea, and mucositis. Ten (31.3%)
patients had >=12 weeks stable disease. The combination PK profiles were
comparable to previously observed monotherapy profiles. Conclusions MTDs were
established for selumetinib in combination with erlotinib or temsirolimus.
Overlapping toxicities prevented the escalation of selumetinib to its recommended
phase II monotherapy dose of 75 mg BID. TRIAL REGISTRATION: ClinicalTrials.gov
NCT00600496; registered 8 July 2009.
PMID- 28424893
TI - Diversity in growth patterns among strains of the lethal fungal pathogen
Batrachochytrium dendrobatidis across extended thermal optima.
AB - The thermal sensitivities of organisms regulate a wide range of ecological
interactions, including host-parasite dynamics. The effect of temperature on
disease ecology can be remarkably complex in disease systems where the hosts are
ectothermic and where thermal conditions constrain pathogen reproductive rates.
Amphibian chytridiomycosis, caused by the pathogen Batrachochytrium dendrobatidis
(Bd), is a lethal fungal disease that is influenced by temperature. However,
recent temperature studies have produced contradictory findings, suggesting that
our current understanding of thermal effects on Bd may be incomplete. We
investigated how temperature affects three different Bd strains to evaluate
diversity in thermal responses. We quantified growth across the entire thermal
range of Bd, and beyond the known thermal limits (T max and T min). Our results
show that all Bd strains remained viable and grew following 24 h freeze (-12
degrees C) and heat shock (28 degrees C) treatments. Additionally, we found that
two Bd strains had higher logistic growth rates (r) and carrying capacities (K)
at the upper and lower extremities of the temperature range, and especially in
low temperature conditions (2-3 degrees C). In contrast, a third strain
exhibited relatively lower growth rates and carrying capacities at these same
thermal extremes. Overall, our results suggest that there is considerable
variation among Bd strains in thermal tolerance, and they establish a new thermal
sensitivity profile for Bd. More generally, our findings point toward important
questions concerning the mechanisms that dictate fungal thermal tolerances and
temperature-dependent pathogenesis in other fungal disease systems.
PMID- 28424894
TI - The integrity of the nucleus of the lateral olfactory tract is essential for the
normal functioning of the olfactory system.
AB - The nucleus of the lateral olfactory tract (nLOT) is a relatively small component
of the cortical pallial amygdala, with peculiar neurogenic, neurochemical and
connectivity patterns. Although it has been suggested that it might be involved
in non-pheromonal olfactory-guided behaviors, particularly feeding, the
functional implications of the nLOT have never been investigated. In view of this
fact, we have tackled this subject by performing a series of behavioral tests and
by quantifying biological and biochemical parameters in sexually naive adult male
rats that were submitted to bilateral excitotoxic lesions of the nLOT. nLOT
lesioned rats had severe olfactory deficits with inability to detect and
discriminate between odors. Additionally, they did not display innate behavioral
responses to biologically relevant chemosignals. Specifically, nLOT-lesioned rats
did not show avoidance towards predator odors or aggressive behaviors towards
intruders, and had severely impaired sexual behavior. In fact, nLOT lesions
abolished preference for odors of receptive females, reduced chemoinvestigatory
behavior and eliminated mounting behavior. nLOT-lesioned rats had normal
circulating levels of testosterone, did not display anxiety- or depressive-like
behaviors, and had unimpaired cognitive functions and fear acquisition and
memory. Altogether, our results suggest that the nLOT integrity is required for
the normal functioning of the olfactory system.
PMID- 28424895
TI - Risk and protective factors for structural brain ageing in the eighth decade of
life.
AB - Individuals differ markedly in brain structure, and in how this structure
degenerates during ageing. In a large sample of human participants (baseline n =
731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the
magnitude of mean change and variability in changes in MRI measures of brain
macrostructure (grey matter, white matter, and white matter hyperintensity
volumes) and microstructure (fractional anisotropy and mean diffusivity from
diffusion tensor MRI). All indices showed significant average change with age,
with considerable heterogeneity in those changes. We then tested eleven
socioeconomic, physical, health, cognitive, allostatic (inflammatory and
metabolic), and genetic variables for their value in predicting these differences
in changes. Many of these variables were significantly correlated with baseline
brain structure, but few could account for significant portions of the
heterogeneity in subsequent brain change. Physical fitness was an exception,
being correlated both with brain level and changes. The results suggest that only
a subset of correlates of brain structure are also predictive of differences in
brain ageing.
PMID- 28424896
TI - Maximum Tongue Pressure is Associated with Swallowing Dysfunction in ALS
Patients.
AB - Maximum tongue pressure (MTP) measurement is a convenient, less invasive
assessment that has been developed to quantify tongue strength; however, it is
unclear whether MTP is useful for the detection of swallowing disorders in
amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to
clarify the relationship between MTP and the characteristics of swallowing
disorders on videofluorography and to determine the usefulness of tongue pressure
measurement for the assessment of swallowing function in ALS patients. Twenty
five ALS patients were evaluated according to the ALS functional rating scale
revised (ALSFRS-R), and their ability to swallow yogurt was observed via
videofluorography. MTP was measured using a device (TPM-01, JMS, Hiroshima)
equipped with a balloon probe. Then, the relationships between the ALSFRS-R
score, swallowing function, and MTP were analyzed. MTP was significantly lower in
the subjects with reduced tongue function (p = 0.002) or with pharyngeal residue
(p = 0.006) than in the subjects with normal characteristics. Bolus formation and
oral transit time and pharyngeal transit time were significantly prolonged among
those with reduced MTP. MTP at a cut-off value of 21.0 kPa was associated with a
full score on the bulbar-related items of the ALSFRS-R. MTP may serve as a new
diagnostic tool for the early detection of swallowing dysfunction in ALS
patients, because of its good relationship with their swallowing characteristics.
PMID- 28424897
TI - First Step in Telehealth Assessment: A Randomized Controlled Trial to Investigate
the Effectiveness of an Electronic Case History Form for Dysphagia.
AB - The need for developing effective telehealth tools for dysphagia management is
high not only for people who live in rural areas, but also for individuals with
mobility/access limitations. We aimed to develop an electronic case History
Tool/form (thereafter, e-HiT) for dysphagia, and compare its effectiveness with
its paper-based version (PBV) on completion time, completeness, independence, and
patient perceptions/satisfaction. Secondarily, we examined associations between
the aforementioned variables and predictor variables, such as age, cognition, and
computer/internet use. Forty adults who expressed concerns with eating/swallowing
participated. To compare both versions, a randomized, controlled two-period
crossover design was used. In Visit 1, Group A completed the e-HiT and Group B
completed the PBV. In Visit 2, Group A completed the PBV and Group B completed
the e-HiT. A satisfaction survey was completed post visits. There were no
statistically significant differences for completion time (p = 0.743),
completeness (p = 0.486), and independence (p = 0.738). Patient
perception/satisfaction was significantly higher with the e-HiT (p = 0.004). In
addition, a significant association was found between completion time and age (p
= 0.0063). Our results indicate that completing the e-HiT is as time efficient as
completing the PBV and that both forms elicit the same amount of information with
no or minimal support. Also, completion of the e-HiT yielded significantly higher
satisfaction responses. This is the first study documenting the effectiveness of
the e-HiT for outpatients with dysphagia, providing evidence that the first step
of a swallowing assessment-case history completion-can be effectively completed
via telehealth by individuals with reliable internet connection and basic
computer literacy skills.
PMID- 28424898
TI - Patient Experiences of Swallowing Exercises After Head and Neck Cancer: A
Qualitative Study Examining Barriers and Facilitators Using Behaviour Change
Theory.
AB - Poor patient adherence to swallowing exercises is commonly reported in the
dysphagia literature on patients treated for head and neck cancer. Establishing
the effectiveness of exercise interventions for this population may be undermined
by patient non-adherence. The purpose of this study was to explore the barriers
and facilitators to exercise adherence from a patient perspective, and to
determine the best strategies to reduce the barriers and enhance the
facilitators. In-depth interviews were conducted on thirteen patients. We used a
behaviour change framework and model [Theoretical domains framework and COM-B
(Capability-opportunity-motivation-behaviour) model] to inform our interview
schedule and structure our results, using a content analysis approach. The most
frequent barrier identified was psychological capability. This was highlighted by
patient reports of not clearly understanding reasons for the exercises,
forgetting to do the exercises and not having a system to keep track. Other
barriers included feeling overwhelmed by information at a difficult time (lack of
automatic motivation) and pain and fatigue (lack of physical capability). Main
facilitators included having social support from family and friends, the desire
to prevent negative consequences such as long-term tube feeding (reflective
motivation), having the skills to do the exercises (physical capability), having
a routine or trigger and receiving feedback on the outcome of doing exercises
(automatic motivation). Linking these findings back to the theoretical model
allows for a more systematic selection of theory-based strategies that may
enhance the design of future swallowing exercise interventions for patients with
head and neck cancer.
PMID- 28424899
TI - A polysomnographic study in parkinsonian patients treated with intestinal
levodopa infusion.
AB - Sleep disorders are very common in advanced Parkinson's disease (PD) and have a
significant negative impact on the quality of life of patients. Questionnaire
based studies suggest that sleep quality might improve following levodopa
carbidopa intestinal gel (LCIG) infusion. The objective of this study was to
evaluate the impact of LCIG infusion and subsequent oral medication changes on
polysomnography (PSG) and sleep symptoms in advanced PD patients. Eleven PD
patients underwent PSG at baseline and after 3.8 +/- 1.2 months of LCIG
treatment. LCIG infusion therapy was halted during PSG. Patients were assessed
with the Unified-PD-rating-Scale and completed the PD-Sleep-Scale-version-2 (PDSS
2), the Epworth Sleepiness Scale and the RBD single question. Subjective sleep
quality improved in all patients. PSG showed a reduction of the number of
awakenings in sleep, a trend towards a lower apnea-hypopnea index and no change
in sleep latency, total sleep time and sleep efficiency. There was a positive
correlation between the number of awakenings and PDSS-2 scores for "difficulty
staying asleep", "muscle cramps of arms or legs" and "urge to move arms or legs".
Motor complications and activities of daily living improved with LCIG. Subjective
sleep quality improved significantly and the PSG study showed a less fragmented
sleep pattern in advanced PD patients treated with LCIG infusion.
PMID- 28424900
TI - Seasonal variation in multiple sclerosis relapse.
AB - Relapses are a characteristic clinical feature of multiple sclerosis (MS), but an
appreciation of factors that cause them remains elusive. In this study, we have
examined seasonal variation of relapse in a large population-based MS cohort and
correlated observed patterns with age, sex, disease course, and climatic factors.
Relapse data were recorded prospectively in 2076 patients between 2005 and 2014.
3902 events were recorded in 1158 patients (range 0-24). There was significant
seasonal variation in relapse rates (p < 0.0001) and this was associated with
monthly hours of sunshine (odds ratio OR 1.08, p = 0.02). Relapse rates were
highest in patients under the age of 30 (OR 1.42, p = 0.0005) and decreased with
age. There was no evidence of different relapse rates for males compared to
females (OR 0.90, p = 0.19). Identification of potentially modifiable
environmental factors associated with temporal variation in relapse rates may
allow alteration of risk on a population basis and alteration of outcome of
established disease once established. Future epidemiological studies should
examine dynamic environmental factors with serial prospective measurements and
biological sampling. Significant seasonal differences in relapse rates highlight
the importance of environmental factors in disease expression and should be taken
into account when planning clinical trials in which relapse frequency is an
outcome. In addition, identification of potentially modifiable factors associated
with this variation may offer unique opportunities for alteration of risk of
relapse and long-term outcome on a population level, and suggest putative
biological mechanisms for relapse initiation.
PMID- 28424901
TI - Driving with a neurodegenerative disorder: an overview of the current literature.
AB - Driving is important for employment, social activities, and for the feeling of
independence. The decision to cease driving affects the quality of life and has
been associated with reduced mobility, social isolation, and sadness. Patients
with neurodegenerative disorders can experience difficulties while driving due to
their cognitive, motor, and behavioral impairments. The aim of this review is to
summarize the available literature on changes in driving competence and behavior
in patients with neurodegenerative disorders, with a particular focus on
Huntington's (HD), Parkinson's (PD), and Alzheimer's disease (AD). A systematic
literature search was conducted in the PubMed/Medline database. Studies using on
road or simulated driving assessments were examined in this review. In addition,
studies investigating the association between cognitive functioning and driving
were included. The review identified 70 studies. Only a few publications were
available on HD (n = 7) compared to PD (n = 32) and AD (n = 31). This review
revealed that driving is impaired in patients with neurodegenerative disorders on
all levels of driving competence. The errors most commonly committed were on the
tactical level including lane maintenance and lane changing. Deficits in
executive functioning, attention, and visuospatial abilities can partially
predict driving competence, and the performance on neuropsychological tests might
be useful when discussing potential driving cessation. Currently, there is no
gold standard to assess driving ability using clinical measures such as
neuropsychological assessments, so more studies are necessary to detect valid
screening tools and develop useful and reliable evidence-based guidelines.
PMID- 28424902
TI - Physical and psychosocial aspects of adolescent and young adults after allogeneic
hematopoietic stem-cell transplantation: results from a prospective multicenter
trial.
AB - PURPOSE: Allogeneic hematopoietic stem-cell transplantation (alloHSCT) is
physically and psychosocially demanding. Among transplant recipients, adolescent
and young adults (AYA) represent a special group, as disease occurs early in
life, resulting in the prospect of long survival time and high burden of alloHSCT
sequelae. However, data focusing on AYA undergoing alloHSCT are rare. METHODS:
Data resulting from a prospective multicenter trial initially focusing on graft
versus-host disease (GvHD) after alloHSCT were reused to analyse the differences
between AYA and elderly patients. In total, data of 205 alloHSCT recipients were
evaluated. Patients completed the FACT-BMT, HAP, SF-36, 24-AM, LOT-R, BSSS, HADS,
and GvHD questionnaires. RESULTS: Median age of AYA and non-AYA patients was 29
and 52 years. Using 24-AM-Test, evaluating personality traits, non-AYA reported
to be more conscientious (p = 0.033). However, AYA described higher quality of
life regarding physical role functioning (p = 0.001), physical functioning (p =
0.002), bodily pain (p = 0.023), and emotional role function (p = 0.027) in the
SF-36. General health perception, vitality, social role functioning, and mental
health were comparable among both groups. On HAP scale, AYA reported higher
maximum (p = 0.003) and adjusted activity scores (p = 0.002), but showed similar
restrictions regarding activity, self-supply, and self-determination. CONCLUSION:
AYA represent a particular group characterized by higher physical well-being and
activity scores, and significantly vary from non-AYA patients in psychosocial
aspects. Studies covering distinctive features of AYA undergoing alloHSCT are
warranted to improve awareness of the special needs of this group.
PMID- 28424903
TI - ZCCHC12, a novel oncogene in papillary thyroid cancer.
AB - PURPOSE: Thyroid cancer is the most common endocrine malignancy worldwide. The
molecular mechanisms underlying thyroid tumorigenesis remain unclear. Some
studies suggested that the ZCCHC12 gene correlates with certain diseases.
However, the function of ZCCHC12 in thyroid cancer has yet to be determined. This
study investigated the role of the ZCCHC12 gene in papillary thyroid cancer
(PTC). METHODS: We conducted a comprehensive analysis of massively parallel whole
transcriptome resequencing of matched PTC tumors and normal tissues in 19
patients. Results showed that the expression of ZCCHC12 was significantly
upregulated in thyroid cancer. qRT-PCR was performed to confirm previous results.
The functions of the ZCCHC12 gene in PTC cell lines (TPC1 and BCPAP) transfected
with small interfering RNA were determined through cell colony formation assay,
migration assay, and invasion assay. RESULTS: The ZCCHC12 gene was remarkably
upregulated in primary PTC tumors in both validated cohort (T:N = 1.80 +/-
2.58:0.23 +/- 0.50, P < 0.01) and TCGA cohort (T:N = 7.63 +/- 3.25:1.55 +/- 1.71,
P < 0.01). We also achieved area under the curve (AUC of ROC) of 87.9% for the
validated cohort while 91.4% for the TCGA cohort to classify PTC tumors and
normal tissues. ZCCHC12 overexpression correlated with lymph node metastasis in
both cohorts (P < 0.05). In in vitro experiments, ZCCHC12 downregulation
significantly inhibited the colony formation, migration, and invasion of PTC
cells. CONCLUSION: Our study indicated that ZCCHC12 gene has important biological
functions and acts as a metastasis-related oncogene in PTC.
PMID- 28424904
TI - Nanoindentation response of cortical bone: dependency of subsurface voids.
AB - Nanoindentation test results in the axial direction of mouse femurs were the
basis for the current study. Although the majority of the nanoindentation curves
showed a reasonable consistency, some curves showed a significantly softer
response. Detailed investigation, using focused ion beam-scanning electron
microscopy, provided that the softer response is due to subsurface cavities such
as lacunae. Finite element models were developed to simulate the nanoindentation
of mice femur cortical bone samples with and without the incorporation of a
single lacuna underneath the bone surface. Based on the material parameters
determined for the cavity-free tissue, numerical simulations were run for
different cases of cavity size, shape, and location. Spherical cavities with
different size were considered at different distances from the surface. The
results showed that subsurface cavities can lead to 50% higher indentation
compared to an indentation in cavity-free material. Continuing with ellipsoidal
cavities with the center located on the load axis, the results showed a nonlinear
dependency of ellipsoid shape. Hence, the shape of the cavity is important for
the nanoindentation response. The influence of horizontal and vertical offsets of
spherical cavities was studied, thereby the results showed that an increasing
horizontal offset caused a decreasing influence of the vertical distance from the
surface. In perspective, the present study provides information that may help to
get deeper knowledge of nanoindentation load-displacement mechanism taking place
in samples with subsurface cavities.
PMID- 28424905
TI - Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid
arthritis and non-systemically reacting antibodies in Egyptian patients.
AB - The aim of this study was to investigate association of protein tyrosine
phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and
activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid
arthritis (RA) susceptibility and to assess potential association with the status
of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)
antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and
neopterin were assayed in serum of 100 unrelated RA patients and 114 controls.
STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the
TaqMan allelic discrimination method. The frequency of STAT4 variant allele was
significantly higher in RA patients than in controls (p = 0.01), while the
variant allele of PTPN22 was identified in only two RA patients, in a
heterozygous form and in none of control subjects. The frequency of STAT4 variant
allele carrier genotypes (GT+TT) was significantly higher among RA patients than
in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and
dominant models. The frequency of RF and anti-CCP positivity was significantly
higher among RA patients carrying T allele genotypes compared to patients
carrying wild genotype (P = 0.02 and 0.04, respectively). No significant
associations between STAT4 variant and serum neopterin or disease activity
parameters were identified. Our study confirmed the association of STAT4
rs7574865 polymorphism with RA and was the first to indicate an association with
RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role
in susceptibility to RA in Egyptian patients.
PMID- 28424906
TI - Prevalence and features of metabolic syndrome in childhood-onset systemic lupus
erythematosus.
AB - To estimate the prevalence and features of metabolic syndrome (MetS) in childhood
onset systemic lupus erythematosus (cSLE), we performed a cross-sectional study
of 76 consecutive cSLE patients and 54 healthy controls, age and sex matched. All
individuals were assessed for anthropometric and MetS features according to World
Health Organization (WHO), NCEP Adult Treatment Panel III (NCEP-ATP III), and
International Diabetes Federation (IDF) criteria. The cSLE patients were further
assessed for clinical and laboratory manifestations, disease activity (Systemic
Lupus Erythematosus Disease Activity Index), cumulative damage (Systemic Lupus
International Collaborating Clinics (SLICC)), and current and cumulative drug
exposures. Sixty-nine (90.8%) patients were female with mean age of 16.8 years
[standard deviation (SD) +/-4.0 years]. Mean disease duration was 4.8 years (SD
+/- 4.1). Based on the WHO MetS criteria, MetS was observed in two (2.6%) cSLE
patients. We observed high prevalence of the MetS in cSLE patients according to
NCEP-ATP III MetS criteria (18.4%) (p = 0.002) and according to IDF MetS criteria
(17.1%) (p = 0.003). We did not observe MetS in the control group. No difference
in cSLE patients <18 and >=18 years was observed. We observed an association
between the presence of MetS and SLICC scores in cSLE <18 years and cumulative
corticosteroid dose adjusted by weight in cSLE >=18 years. This study showed that
MetS is frequently observed in cSLE using NCEP-ATP III MetS criteria and IDF MetS
criteria. The identification of MetS is important to indicate cardiovascular
morbidity and mortality in cSLE.
PMID- 28424907
TI - The added value of synovial fluid centrifugation for monosodium urate and calcium
pyrophosphate crystal detection.
AB - The aim of the study was to assess the added value of synovial fluid (SF)
centrifugation for microscopic monosodium urate (MSU) and calcium pyrophosphate
(CPP) crystal detection in patients with arthritis. This is a prospective
observational study using SF samples from joints of patients undergoing joint
arthrocentesis. Two blinded observers assessed the SF smears by polarized light
microscopy for the presence of crystals before as well as after centrifugation.
SF samples were collected from 98 patients with arthritis. After exclusion, 87
samples were eligible for inclusion. Of each sample, 2 smears before and after
centrifugation were prepared and microscopically examined, resulting in 348
smears per observer. Observer 1 identified MSU crystals in 18.4% and CPP in 9.2%
of the smears before as well as after centrifugation. No extra MSU crystal
positive smears were identified after centrifugation. However, centrifugation
yielded 4 additional CPP crystal-positive smears. Observer 2 identified MSU
crystals in 15.5% and CPP crystals in 6.3% of the smears before as well as after
centrifugation. Centrifugation yielded 2 additional MSU crystal-positive smears
and 4 CPP crystal-positive smears. Monosodium urate crystals were well recognized
without centrifugation. Centrifugation of SF had limited additional value for
increasing the amount of MSU-positive smears. However, CPP crystals were
identified in a higher number of smears after centrifugation than before.
Therefore, centrifugation may be of additional value in selected patients with
suspected calcium pyrophosphate deposition disease and to a lesser extent for
gout.
PMID- 28424908
TI - Delayed closure of open abdomen in septic patients treated with negative pressure
wound therapy and dynamic fascial suture: the long-term follow-up study.
AB - INTRODUCTION: Negative pressure wound therapy (NPWT) is widely used in the
treatment of open abdomen (OA). The use of dynamic fascial sutures (DFS)
increases the rate of successful delayed closure by reducing fascial
lateralization. We recently published a prospective controlled trial including 87
patients undergoing abdominal surgery for secondary peritonitis between 2007 and
2012. Patients were treated with NPWT and DFS for approximation of fascial edges.
The present study represents a follow-up assessment of these patients 5-9 years
after OA treatment with NPWT and DFS. METHODS: The 39 patients still alive were
included in the recent study according to the protocol of our last study in 2013.
All patients received a questionnaire regarding long-term complications after OA
treatment between 2007 and 2012. Mean follow-up was 5-9 years. Analyzed
parameters included pain, the presence of incisional hernia, and subsequent
surgical interventions. Results were analyzed quantitatively. RESULTS: One
patient had deceased since the last publication in 2013, and hence 38 patients
were included in the current study. The median age was 60.9 (25.2-86.1) years,
and 17 (44.7%) were females. Overall 56.3% of the original 87 patients had died
during the long-term follow-up period. 21 patients (55.3%) answered the
questionnaire. Six (28.6%) declared that they suffered from pain in the previous
operating field, five (23.8%) at rest, and three (14.3%) during exercise. In five
patients (23.8%), pain lasted for more than 3 months. One patient (4.8%) still
requires analgesic treatment. Among the 21 patients, seven (33.3%) were found to
have incisional hernias. Three hernias (42.9%) were treated by surgery.
CONCLUSION: Incisional hernia rates after OA treatment remain high, but are
accompanied by little pain. The ideal technique of fascial closure after NPWT
should be investigated in further research.
PMID- 28424909
TI - Comparison of clinical outcomes and quality of life between laparoscopic and open
central pancreatectomy with pancreaticojejunostomy.
AB - BACKGROUND: The studies comparing laparoscopic and open central pancreatectomy
with pancreaticojejunostomy are limited. This study aimed to compare clinical
outcomes and quality of life of patients undergoing laparoscopic and open central
pancreatectomy with pancreaticojejunostomy. METHODS: Between December 1997 and
December 2015, patients who underwent central pancreatectomy with
pancreaticojejunostomy were reviewed. Patients were divided into 2 groups as
laparoscopic central pancreatectomy (LCP) and open central pancreatectomy (OCP).
Data considered for comparison analysis were patient demographics, intraoperative
variables, morbidity, postoperative hospital stay, mortality, pathologic
findings, and quality of life (SF-36 questionnaire). RESULTS: Thirty-six patients
(17 LCP and 19 OCP) were included in the final analysis. Baseline characteristics
were similar in the 2 groups. The operating time (280.4 +/- 33.6 vs. 290.5 +/-
62.5 min, p = 0.455) were similar between two groups. LCP group showed
significantly lower estimated blood loss (76.4 +/- 70.3 vs. 390.3 +/- 279.0 ml, p
= 0.001), shorter first flatus time (2.4 +/- 0.9 vs. 3.9 +/- 1.3 days, p =
0.001), and shorter diet start time (4.1 +/- 2.2 vs. 6.1 +/- 2.4 days, p =
0.030). However, the postoperative hospital stay was not significantly different
between two groups (15.6 +/- 12.1 vs. 24.0 +/- 27.5 days, p = 0.347).
Postoperative outcomes, including morbidity (58.8 vs. 52.6%, p = 0.749),
pancreatic fistula rates (>=grade B: 17.6 vs. 36.8%, p = 0.106), and mortality,
were similar in the 2 groups. The median follow-up period was 45 months (range 4
216 months). No local recurrence or distant metastasis was detected in either
group. On the follow-up survey, the total quality of life score (702.9 +/- 47.9
vs. 671.8 +/- 94.1), physical health score (353.9 +/- 24.8 vs. 326.6 +/- 67.6)
and mental health score (349.0 +/- 26.5 vs. 345.2 +/- 34.6) were higher in the
LCP group compared with the OCP group. However, these differences were not
statistically significant (p > 0.05). The score in role physical (100 vs. 73.1 +/
4.8, p = 0.042) was significantly higher in LCP group, and not statistically
significant in other areas (p > 0.05). CONCLUSIONS: LCP with
pancreaticojejunostomy is safe and feasible for benign or borderline malignant
lesions in the pancreatic neck and proximal body. Compared to OCP, LCP is
associated with lower estimated blood loss, faster recovery, and better quality
of life.
PMID- 28424910
TI - Erratum to: Laparoscopic image-based navigation for microwave ablation of liver
tumors: A multi-center study.
PMID- 28424911
TI - Long-term outcomes of endoscopic resection of gastric GISTs.
AB - OBJECTIVE: Although the endoscopic treatment of gastric stromal tumors is a
recently accepted therapy, the long-term outcomes of this approach remain
unknown. The aims of this study were to assess the long-term effectiveness and
safety of endoscopic resection for gastric GISTs. METHODS: A total of 60
consecutive patients undergoing endoscopic resection of gastric GISTs were
enrolled in a retrospective single-center study. Clinical data, perioperative
complications, histopathologic characteristics of the tumors, and long-term
outcomes were recorded. RESULTS: Sixty patients successfully underwent complete
resection of lesions, including 25 cases of endoscopic submucosal dissection
(ESD) and 35 cases of endoscopic full-thickness resection (EFTR), with an average
tumor size of 1.76 +/- 1.55 cm (range 0.5-7.6 cm). The average operation time was
43.97 +/- 26.95 min (range 11.7-138.9 min). Two cases were observed with an
intraoperative hemorrhage of 200 mL, which were successfully managed by
hemostatic forceps. Perforations of 2-11 mm of ESD occurred in four cases (4/25)
and were well closed with endoclips, with no conversions to surgical operation.
Mucosal laceration of esophagus occurred in 1 case, when a large tumor was
removed. The average length of hospitalization was 6.50 +/- 3.06 days (range 3-21
days). Out of a total of 60 patients, 44 (73.3%) were at very low risk, 10
(16.7%) were at low risk, 5 (8.3%) were at intermediate risk, and 1 (1.7%) was at
high risk. All patients were followed-up for 36.15 +/- 12.92 months (range 14-73
months). Primary tumor recurrence occurred in 1 patient who underwent a second
operation after 32 months, and no other cases were observed to have either tumor
recurrence or metastasis. CONCLUSIONS: For long-term outcomes, endoscopic
resection of ESD or EFTR is a safe and effective approach for removing gastric
stromal tumors (<5 cm), and it can be a resection technique for them with no
metastasis.
PMID- 28424912
TI - Rescue EUS-guided intrahepatic biliary drainage for malignant hilar biliary
stricture after failed transpapillary re-intervention.
AB - BACKGROUND: Treatment of unresectable malignant hilar biliary stricture (UMHBS)
is challenging, especially after failure of repeated transpapillary endoscopic
stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS
IBD) is a recent technique for intrahepatic biliary decompression, but
indications for its use for complex hilar strictures have not been well studied.
The aim of this study was to assess the feasibility and safety of EUS-IBD for
UMHBS after failed transpapillary re-intervention. METHODS: Retrospective
analysis of all consecutive patients with UMHBS of Bismuth II grade or higher
who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated
transpapillary interventions. The technical success, clinical success, and
complication rates were evaluated. Factors associated with clinical
ineffectiveness of EUS-IBD were explored. RESULTS: A total of 30 patients (19
women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the
study period. Hilar biliary stricture morphology was classified as Bismuth II,
III, or IV in 5, 13, and 12 patients, respectively. The median number of
preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required
because the following procedures failed: duodenal scope insertion (n = 4),
accessing the papilla after duodenal stent insertion (n = 5), or achieving
desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD
was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22
of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was
managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no
procedure-related mortality. On multivariable analysis, Bismuth IV stricture
predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P =
0.035). CONCLUSIONS: EUS-IBD may be a feasible and effective rescue alternative
with few major complications after failed transpapillary endoscopic re
intervention in patients with UMHBS, particularly for Bismuth II or III
strictures.
PMID- 28424913
TI - Can further gastrectomy be avoided in patients with incomplete endoscopic
resection?
AB - BACKGROUND: Endoscopic resection (ER) is a widely accepted treatment for patients
with early gastric cancer (EGC) with no lymph node metastasis. Occasionally,
however, additional surgery is needed due to an incomplete resection. The purpose
of this study was to detect clinical factors which might identify patients at
greater risk of additional surgery after ER and to suggest an alternative
treatment strategy for these patients. METHODS: This study retrospectively
analyzed 350 patients with gastric cancer who underwent radical gastrectomy and
lymphadenectomy after ER in a single institution between July 2004 and July 2014.
Risk factors for incomplete resection were identified using binary logistic
multiple regression tests and a classification and regression tree analysis.
RESULTS: Residual cancer cells were found in the remnant stomach or lymph node in
96 patients (27.4%). In multivariate analysis, lymphovascular invasion (p <
0.001, odds ratio [OR] 5.619) and depth of invasion greater than the second
submucosal layer (SM2) (p < 0.01, OR 3.224) were independent risk factors for
lymph node metastasis. Positive resection margin (p < 0.001, OR 7.565), depth of
invasion to mucosa (M) and the first submucosal layer (SM1) (p < 0.001, OR
4.219), and size over 3 cm (p < 0.029, OR 2.306) were significant risk factors
for residual tumor in the remnant stomach. Of 106 patients who had invasion of
the M or SM1 without lymphatic invasion at the time of ER, residual cancer was
found in 53 patients. Of these 53 patients, 50 (94.3%) had residual cancer in the
mucosal layer and only one had lymph node metastasis. CONCLUSION: In patients
with EGC with M or SM1 invasion without lymphovascular invasion at the time of
ER, who had an incomplete resection, additional endoscopic treatment or close
monitoring can be performed instead of additional surgery, especially in patients
who are unable to tolerate gastrectomy, for example elderly patients or those
with comorbidities.
PMID- 28424914
TI - Association of femoral head and acetabular fractures on computerized tomography:
correlation with the Judet-Letournel classification.
AB - PURPOSE: Tha aims of this study were to identify the incidence of femoral head
fractures in the setting of acetabular fractures and to determine the
relationship between acetabular fracture pattern, the degree of acetabular
fracture displacement, and the incidence of femoral head fractures. MATERIALS AND
METHODS: This is a retrospective cross-sectional study of 274 patients with 300
acetabular fractures diagnosed on pelvic CT. Acetabular fractures were
categorized using the Judet-Letournel classification system. RESULTS: Femoral
head fractures were present in 18.0% of acetabular fractures. Fracture patterns
with a posterior wall component had a very high (56.3%) incidence of femoral head
fracture. Anterior column and anterior column with posterior hemitransverse
fractures have a very low (3.4%) incidence of femoral head fracture. Anterior hip
dislocation had a 66.7% incidence of femoral head fracture, while posterior
dislocation had a 71.9% incidence. Acetabular fractures displaced by more than 5
mm had a 26.9% incidence of femoral head fracture, while acetabular fracture
displaced less than 5 mm had only 4.2% incidence of femoral head fracture.
CONCLUSION: Femoral head fractures are a very common associated finding in
patients presenting with acetabular fractures. In patients with a posterior wall
component of the fracture or associated hip dislocation, a femoral head fracture
is more likely than not present. Conversely, in acetabular fractures with less
than 5 mm displacement or anterior column fractures without posterior acetabular
involvement, femoral head fractures are very unlikely in the absence of a
dislocation event.
PMID- 28424915
TI - Optimal eye movement strategies: a comparison of neurosurgeons gaze patterns when
using a surgical microscope.
AB - BACKGROUND: Previous studies have consistently demonstrated gaze behaviour
differences related to expertise during various surgical procedures. In micro
neurosurgery, however, there is a lack of evidence of empirically demonstrated
individual differences associated with visual attention. It is unknown exactly
how neurosurgeons see a stereoscopic magnified view in the context of micro
neurosurgery and what this implies for medical training. METHOD: We report on an
investigation of the eye movement patterns in micro-neurosurgery using a state-of
the-art eye tracker. We studied the eye movements of nine neurosurgeons while
performing cutting and suturing tasks under a surgical microscope. Eye-movement
characteristics, such as fixation (focus level) and saccade (visual search
pattern), were analysed. RESULTS: The results show a strong relationship between
the level of microsurgical skill and the gaze pattern, whereas more expertise is
associated with greater eye control, stability, and focusing in eye behaviour.
For example, in the cutting task, well-trained surgeons increased their fixation
durations on the operating field twice as much as the novices (expert, 848 ms;
novice, 402 ms). CONCLUSIONS: Maintaining steady visual attention on the target
(fixation), as well as being able to quickly make eye jumps from one target to
another (saccades) are two important elements for the success of neurosurgery.
The captured gaze patterns can be used to improve medical education, as part of
an assessment system or in a gaze-training application.
PMID- 28424916
TI - Bilateral pallidotomy for Meige syndrome.
AB - Meige syndrome (MS) is usually described as a combination of blepharospasm with
oromandibular dystonia. There are a large number of case reports of deep brain
stimulation (DBS) of the globus pallidus internus (GPI) for MS and only one
report of unilateral pallidotomy (PT). We report the first case of staged
bilateral PT for treatment of a patient with MS using intraoperative high
frequency stimulation in order to predict and prevent postoperative deficit.
There was a significant improvement of the Burk-Fahn-Marsden dystonia rating
scale from 26 to 3. There were no adverse postoperative neurological and
neuropsychological events.
PMID- 28424917
TI - Cubital tunnel syndrome caused by ganglion cysts: a review of 59 cases.
AB - BACKGROUND: Cubital tunnel syndrome caused by ganglion cysts is rare and reports
are few. This study aimed to review a patient cohort with ganglion cysts in the
cubital tunnel and identify prognostic factors. METHODS: Fifty-seven patients (59
extremities; McGowan grade I, 4; IIa, 4; IIb, 3; III, 48) were evaluated
retrospectively with a minimum follow-up of 2 years. Extraneural cysts were
excised completely, while intraneural cysts were incised and drained. All cases
underwent subcutaneous transposition. Spearman's rank correlation and the ordinal
logistic regression model were used to assess the effect of independent variables
on the postoperative McGowan grade. RESULTS: VAS pain and weakness, 2-PD, key
pinch strength, grip strength, first dorsal interosseous muscle strength,
Wartenberg sign, and claw hand all improved significantly. DASH scores improved
from an average of 43.8 points preoperatively to 10.7 points postoperatively.
According to the modified Bishop scoring system, 55 extremities (93.2%) were
graded good or excellent. At the last follow-up, 29 hands (49.2%) returned to
normal, and improvement by at least one McGowan grade was reached in 51 cases
(86.4%). Older age, smoking, and shorter postoperative follow-up were associated
with a higher postoperative McGowan grade. CONCLUSIONS: Satisfactory surgical
outcomes could be expected in these patients following subcutaneous transposition
with excision of extraneural cysts and draining of intraneural cysts. Older age,
smoking, and shorter postoperative follow-up were found to be independent risk
factors for poor outcomes.
PMID- 28424918
TI - Risk factors for surgical site infections among 1,772 patients operated on for
lumbar disc herniation: a multicentre observational registry-based study.
AB - BACKGROUND: There are no previous studies evaluating risk factors for surgical
site infections (SSIs) and the effectiveness of prophylactic antibiotic treatment
(PAT), specifically for patients operated on for lumbar disc herniation. METHOD:
This observational multicentre study comprises a cohort of 1,772 consecutive
patients operated on for lumbar disc herniation without laminectomy or fusion at
23 different surgical units in Norway. The patients were interviewed about SSIs
according to a standardised questionnaire at 3 months' follow-up. RESULTS: Three
months after surgery, 2.3% of the patients had an SSI. Only no PAT (OR = 5.3, 95%
CI = 2.2-12.7, p< 0.001) and longer duration of surgery than the mean time (68
min) (OR = 2.8, 95% CI = 1.2-6.6, p = 0.02) were identified as independent risk
factors for SSI. Numbers needed to have PAT to avoid one SSI was 43. CONCLUSIONS:
In summary, this study clearly lends support to the use of PAT in surgery for
lumbar disc herniation. Senior surgeons assisting inexperienced colleagues to
avoid prolonged duration of surgery could also reduce the occurrence of SSI.
PMID- 28424919
TI - Nerve enlargement in an unusual case of inflammatory neuropathy and new gene
mutation-morphology is the key.
PMID- 28424920
TI - Epidemiological information of dementia with Lewy bodies.
PMID- 28424921
TI - Evolution of psychological condition in caregivers of patients with disorders of
consciousness: a longitudinal study.
AB - The aim of this study is to evaluate mood disorders and needs in caregivers of
disorders of consciousness (DOC) patients during the admission to
Neurorehabilitation Unit. A total of 80 caregivers was enrolled and divided in
two groups (caregivers of vegetative state-VS patients and caregivers of
minimally conscious state-MCS patients). Paired sample t tests were carried out
to test differences between baseline observation (T0) and after 6 months (T1).
Caregivers of VS patients showed an improvement between T0 and T1 especially, in
vitality, mean health, Beck Depression Inventory (BDI-II), Spielberger State
Trait Anxiety Inventory-Y (STAI-Y), Prolonged Grief Disorder (PG 12) and
Caregiver Needs Assessment (CNA). On the other hand, caregivers of MCS patients
showed a significant improvement in: BDI II, STAI Y and CNA. These data confirmed
that the presence of psychological problems, the quality of life and the
psychological wellbeing of caregivers of DOC patients improved over the time.
PMID- 28424922
TI - Assistive technology for ultrasound-guided central venous catheter placement.
AB - This study evaluated the existing technology used to improve the safety and ease
of ultrasound-guided central venous catheterization. Electronic database searches
were conducted in Scopus, IEEE, Google Patents, and relevant conference databases
(SPIE, MICCAI, and IEEE conferences) for related articles on assistive technology
for ultrasound-guided central venous catheterization. A total of 89 articles were
examined and pointed to several fields that are currently the focus of
improvements to ultrasound-guided procedures. These include improving needle
visualization, needle guides and localization technology, image processing
algorithms to enhance and segment important features within the ultrasound image,
robotic assistance using probe-mounted manipulators, and improving procedure
ergonomics through in situ projections of important information. Probe-mounted
robotic manipulators provide a promising avenue for assistive technology
developed for freehand ultrasound-guided percutaneous procedures. However, there
is currently a lack of clinical trials to validate the effectiveness of these
devices.
PMID- 28424923
TI - Shear wave velocity of the healthy thyroid gland in children with acoustic
radiation force impulse elastography.
AB - PURPOSE: Acoustic radiation force impulse imaging is a kind of shear wave
elastography that can be used in children for differentiating thyroid
pathologies. Possible changes in the healthy thyroid gland in children may create
difficulties in the use of shear wave velocities (SWV) in thyroid pathologies.
The aim of this study was to define the normal values of SWV for the healthy
thyroid gland in children, elucidate the correlation of the SWV values with
potential influencing factors, and evaluate intra-operator reproducibility of the
SWV. METHODS: Between January 2015 and December 2015, a total of 145 healthy
children (81 girls, 64 boys; mean age, 10.5 +/- 3.14 years; range 6-17 years)
were enrolled in the study. The SWV and volume of the thyroid gland were
determined. RESULTS: The mean shear wave velocity of the thyroid gland was 1.22
+/- 0.20 m/s. There was no correlation between age and the mean SWV of the
thyroid gland (Spearman Rho = 0.049, p = 0.556). There was also no correlation
between the thyroid gland volume or BSA and the mean SWV. The only correlation
detected was between BSA and total thyroid gland volume (p < 0.001). CONCLUSION:
In the present study, the SWV of the healthy thyroid gland in children was
determined. There was no correlation between the SWV of the thyroid gland and
age, BSA, or thyroid gland volume.
PMID- 28424924
TI - Effects of GW002, a novel recombinant human glucagon-like peptide-1 (GLP-1)
analog fusion protein, on CHO recombinant cells and BKS-db mice.
AB - AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes
mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which
limits its clinical application. The purpose of this study was to evaluate the
effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by
linking the human GLP-1 analog C-terminus to the N-terminus of human serum
albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether
GW002 can activate the GLP-1 receptor in cells, the level of luciferase
expression was evaluated in vitro. In vivo, body weight, food intake, non-fasting
and fasting blood glucose, oral glucose tolerance test, blood glucose and insulin
levels, liver histology, liver function parameters and antibody levels in BKS-db
mice were investigated to evaluate the effects of GW002. Albiglutide was chosen
as a positive comparator. RESULTS: Cyclic adenosine monophosphate levels were
increased in a dose-dependent manner in cells. In vivo studies demonstrated that
GW002 lowers non-fasting and fasting blood glucose levels and improves glucose
tolerance and insulin secretion in BKS-db mice. The degree of hepatic steatosis
and hepatic biochemical indexes was also decreased. In this study, the mice body
weight was not reduced significantly. CONCLUSIONS: The above results showed that
the efficacy of GW002 in BKS-db mice displayed a significant hypoglycemic effect,
which indicated that GW002 might be a potential candidate for the treatment of
T2DM.
PMID- 28424925
TI - Cross Vertical Mattress Suturing with Basilar Tightening During the Correction of
Inverted Nipple in 30 Cases.
AB - OBJECTIVE: To investigate the efficacy of cross vertical mattress suturing with
basilar tightening during the correction of inverted nipple. METHODS: Thirty
patients with inverted nipples underwent cross vertical mattress suturing with
basilar tightening. The postoperative results were recorded. RESULTS: All the
patients were followed up for 6 months to 2 years. The results of 28 cases were
satisfactory, and there was no recurrence. Two patients relapsed, and a mild
depression was formed. They were satisfied with the results after the second
correction. CONCLUSION: The method of cross vertical mattress suturing with
basilar tightening has been applied to treat inverted nipple, with minimal
trauma, which provides a reliable guarantee for a long-term effect. It is worthy
to be widely used in clinical practice. LEVEL OF EVIDENCE IV: This journal
requires that authors assign a level of evidence to each article. For a full
description of these Evidence-Based Medicine ratings, please refer to the Table
of Contents or the online Instructions to Authors www.springer.com/00266 .
PMID- 28424926
TI - Erratum to: Co2/Erbium:YAG/Dye Laser Combination: An Effective and Successful
Treatment for Angiofibromas in Tuberous Sclerosis.
PMID- 28424927
TI - Development of new extra-glandular manifestations or associated auto-immune
diseases after establishing the diagnosis of primary Sjogren's syndrome : A long
term study of the Antonius Nieuwegein Sjogren (ANS) cohort.
AB - To investigate in a long-term study, the development of new extra-glandular
manifestations (EGM) or associated auto-immune diseases (AID) from 1 year after
establishing the diagnosis of primary Sjogren's syndrome (pSS). The primary goal
was to examine the frequency and type of these manifestations and to find out
which demographic, clinical and serological profile was most at risk. All
outpatients diagnosed with primary Sjogren's syndrome were included in a
retrospective study, with at least one check-up per year, from June 1991 until
August 2015. Patients also fulfilling the criteria for concomitant connective
tissue disorders were excluded. Data were collected with respect to the
cumulative prevalence of a new EGM or associated AID. 140 patients were included
in the final analysis. After 10 years of follow-up, the cumulative incidence of a
new EGM or associated AID was 30.7%. The most frequent events were
polyneuropathy, interstitial lung disease, (poly)arthritis, discoid lupus
erythematosus (LE)/subacute cutaneous LE and Hashimoto's disease. Non-Hodgkin
lymphoma was not diagnosed during the follow-up. Patients without chronic benign
pain syndrome (CBP) (HR 2.13; 95% CI [0.94-4.76]; p = 0.061), but in particular
those with cryoglobulins (HR 2.87; 95% CI [1.20-6.86]; p = 0.013), developed more
events. Age at diagnosis, gender, the presence of ANA, anti-Ro/SSA, anti-La/SSB,
IgM-RF, decreased levels of C3 or C4, or hypergammaglobulinaemia did not show any
statistically significant differences. The burden of disease in pSS is higher
than expected due to the development of EGM or associated AID. Therefore, we
recommend long-term follow-up of all pSS patients, particularly those with
cryoglobulinaemia.
PMID- 28424928
TI - Metal-metal bonding in 1st, 2nd and 3rd row transition metal complexes: a
topological analysis.
AB - A topological analysis based on density functional electronic and spin densities
of the bonding characteristics in a series of Fe, Ru, Os, Tc and Rh dimers and
trimers bridged, respectively, by MU-1,8-naphthyridine (nap) and MU-2,2'
dipyridylamine (dpa) is presented. By this simple qualitative analysis, we were
able to determine the electronic ground state and correlated bonding order for a
number of complexes potentially involved in extended metal atom chains (EMAC).
Furthermore, we showed in the Ru dimer that it was possible to control the spin
state simply by changing the bonded counter-anion. Graphical Abstract Electron
localization analysis of the bonding properties in [M2(nap)4Cl2]2+ and
[M3(dpa)4(Cl2] complexes.
PMID- 28424929
TI - Assessment of TDDFT- and CIS-based methods for calculating fluorescence spectra
of (dibenzoylmethanato)boron difluoride exciplexes with aromatic hydrocarbons.
AB - The applicabilities of various CIS- and TDDFT-based procedures to the calculation
of the fluorescence spectra of DBMBF2 exciplexes with aromatic hydrocarbons are
analyzed. It is shown that a reasonable agreement between the calculated and
experimental fluorescence spectra is obtained when a combined procedure is used.
In this combined procedure, the geometries of the exciplexes are optimized
beforehand using the CIS method with an empirical dispersion correction, while
the exciplex transition energies are calculated at the optimized geometries using
the CIS(D) method or the TDDFT approach with double-hybrid B2PLYP and mPW2PLYP
functionals.
PMID- 28424930
TI - Comparison of laparoscopic hernia repair and open herniotomy in children: a
retrospective cohort study.
AB - BACKGROUND: Laparoscopic hernia repair in infancy and childhood is still
debatable. The objective of this study is to compare laparoscopic-assisted hernia
repair (LH) versus open herniotomy (OH) as regards operative time, postoperative
complications, recurrence rate, and contralateral metachronous hernia rate.
METHODS: We analyzed all the patients with inguinal hernia who underwent surgery
in our hospital from January 1, 2015 to December 31, 2015. There were 1125
patients, of which 202 patients received laparoscopic inguinal hernia repair
(group A) and 923 patients received open herniotomy (group B). We recalled all
the patients' records to identify operative time, postoperative hydrocele
formation, and contralateral patent processus vaginalis (CPP) detection; we
recalled all the patients' parents to identify the ipsilateral and contralateral
recurrence and the testis position. RESULTS: During the study period, the lost to
follow-up rate is 9.9% in group A and 14.1% in group B. The mean follow-up period
was about 10.1 months. The mean operative time for females with bilateral hernia
in group A was much shorter than that for those in group B (P = 0.001). The
postoperative hydrocele formation rate in group A was 1.5%, compared with 8.2% in
group B (P = 0.001). The recurrence rate was 0.64% in group A, whereas in group B
the recurrence rate was 0.46%. Of patients with unilateral hernia, none in group
A experienced a contralateral metachronous hernia (MH) compared with 10.1% in
group B (P < 0.001) and 65% MH appeared in 3 months after the first hernia
repair. Females and patients with initial left-sided hernia tended to have a
contralateral MH after the first open hernia repair. CONCLUSION: Laparoscopic
hernia repair in children is safe and effective, especially for female patients
and patients with initial left-sided hernia. We recommend repairing the CPP
simultaneously when performing laparoscopic procedures.
PMID- 28424931
TI - Contemporary engagement with social media amongst hernia surgery specialists.
AB - PURPOSE: Healthcare professional engagement is increasing. This study aims to
identify levels of adoption and engagement of several social media platforms by a
large international cohort of hernia surgery specialists. METHODS: Hernia
specialists attending the 38th International Congress of the European Hernia
Society were identified. A manual search was then performed on Twitter,
ResearchGate, and LinkedIn to identify those who had named accounts. Where
accounts were identified, data on markers of utilisation were assessed. RESULTS:
759 surgeons (88.5% male) from 57 countries were identified. 334 surgeons (44%)
engaged with a social media platform. 39 (5.1%) had Twitter accounts, 189 (24.9%)
had ResearchGate accounts and 265 (34.9%) had LinkedIn accounts. 137 surgeons
(18.1%) had accounts on 2 or more social media platforms. There was no gender
association with social media account ownership (p > 0.05). Engagement in one
social media platform was associated with increased engagement and utilisation on
other platforms; LinkedIn users were more likely to have Twitter accounts (p <
0.001) and ResearchGate profiles (p < 0.001). Surgeons on all three SM platforms
were more likely to have high markers of engagement across all SM platforms
(multiple outcomes, p < 0.05). Geographical variation was noted with UK and South
American Surgeons being more likely to be present on Twitter than their
counterparts (p = 0.031). CONCLUSIONS: The level of engagement with social media
amongst Hernia surgeons is similar to other surgical specialities. Geographical
variation in SM engagement is seen. Engagement with one SM platform is associated
with presence on multiple platforms.
PMID- 28424932
TI - Inverse relationship of Ca2+-dependent flagellar response between animal sperm
and prasinophyte algae.
AB - Symmetry/asymmetry conversion of eukaryotic flagellar waveform is caused by the
changes in intracellular Ca2+. Animal sperm flagella show symmetric or asymmetric
waveform at lower or higher concentration of intracellular Ca2+, respectively. In
Chlamydomonas, high Ca2+ induces conversion of flagellar waveform from asymmetric
to symmetry, resulting in the backward movement. This mirror image relationship
between animal sperm and Chlamydomonas could be explained by the distinct calcium
sensors used to regulate the outer arm dyneins (Inaba 2015). Here we analyze the
flagellar Ca2+-response of the prasinophyte Pterosperma cristatum, which shows
backward movement by undulating four flagella, the appearance similar to animal
sperm. The moving path of Pterosperma shows relatively straight in artificial
seawater (ASW) or ASW in the presence of a Ca2+ ionophore A23187, whereas it
becomes circular in a low Ca2+ solution. Analysis of flagellar waveform reveals
symmetric or asymmetric waveform propagation in ASW or a low Ca2+ solution,
respectively. These patterns of flagellar responses are completely opposite to
those in sperm flagella of the sea urchin Anthocidaris crassispina, supporting
the idea previously proposed that the difference in flagellar response to Ca2+
attributes to the evolutional innovation of calcium sensors of outer arm dynein
in opisthokont or bikont lineage.
PMID- 28424933
TI - Fact and controversies when assessing fluid responsiveness.
PMID- 28424934
TI - Synthesis, antioxidant and antimicrobial activities of novel thiopyrano[2,3
d]thiazoles based on aroylacrylic acids.
AB - Here it is described the synthesis, antioxidant and antimicrobial activity
determination of novel rel-([Formula: see text])-6-benzoyl-7-phenyl-2-oxo-3,5,6,7
tetrahydro-2H-thiopyrano[2,3-d]thiazole-5-carboxylic acids. The target compounds
were obtained in good yields from 5-arylidene-4-thioxo-2-thiazolidinones and
[Formula: see text]-aroylacrylic acids via regio- and diastereoselective hetero
Diels-Alder reaction. The stereochemistry of the cycloaddition was confirmed by
NMR spectra. The antioxidant and antimicrobial activity screening identified 7
compounds (3c, 3e, 3f, 3g, 3k, 3l, 3p) with a high level of free radical
scavenging (43-77% DPPH assay), and compounds with significant influence on
Staphylococcus aureus, Bacillus subtilis and Candida albicans (MIC 3.13-6.25
[Formula: see text]), but slight effect on Escherichia coli.
PMID- 28424935
TI - A Ratiometric and near-Infrared Fluorescent Probe for Imaging Cu2+ in Living
Cells and Animals.
AB - We have rationally constructed a novel ratiometric and near-infrared Cu2+
fluorescent probe based on a tricarbocyanine chromophore. The new probe NIR-Cu
showed a ratiometric fluorescent response to Cu2+ with a large emission
wavelength shift (up to 142 nm) in the far-red to near-infrared region. The probe
also displayed a large variation in the fluorescence ratio (I636/I778) to Cu2+
species with high sensitivity and selectivity. Additionally, the developed probe
NIR-Cu was suitable for fluorescence imaging of Cu2+ in living cells and mice.
PMID- 28424936
TI - Preoperative Chemoradiotherapy Versus Perioperative Chemotherapy for Patients
With Resectable Esophageal or Gastroesophageal Junction Adenocarcinoma.
AB - BACKGROUND: This study compares neoadjuvant chemoradiotherapy (nCRT) with
perioperative chemotherapy (pCT) for patients with resectable esophageal or
gastroesophageal junction (GEJ) adenocarcinoma in terms of toxicity,
postoperative complications, pathologic response, and survival. METHODS: This
study retrospectively analyzed and compared 313 patients with resectable
esophageal or GEJ adenocarcinoma treated with either nCRT (carboplatin/paclitaxel
41.4 Gy, n = 176) or pCT (epirubicin, cisplatin and capecitabine, n = 137).
RESULTS: The baseline and tumor characteristics were similar in both groups. The
ability to deliver all planned preoperative cycles was greater in the nCRT group
(92.0 vs. 76.6%). Whereas nCRT was associated with a higher rate of grades 3 and
4 esophagitis, pCT was associated with a higher rate of grades 3 and 4
thromboembolic events, febrile neutropenia, nausea, vomiting, diarrhea, hand-foot
syndrome, mucositis, cardiac complications, and electrolyte imbalances. Two
patients in the pCT group died during neoadjuvant treatment due to febrile
neutropenia. More postoperative cardiac complications occurred in the nCRT group.
All other postoperative complications and the in-hospital mortality rate (nCRT,
4.7%; pCT, 2.3%) were comparable. The pathologic complete response (pCR) rate was
15.1% after nCRT and 6.9% after pCT. Radicality of surgery was comparable (R0:
93.0 vs. 91.6%). The median overall survival was 35 months after nCRT versus 36
months after pCT. CONCLUSION: For patients with esophageal or GEJ adenocarcinoma,
chemoradiotherapy with paclitaxel, carboplatin and concurrent radiotherapy, and
perioperative chemotherapy with epirubicin, cisplatin, and capecitabin lead to
equal oncologic outcomes in terms of radical resection rates, lymphadenectomy,
patterns of recurrent disease, and (disease-free) survival. However, neoadjuvant
chemoradiotherapy is associated with a considerably lower level of severe adverse
events and should therefore be the preferred protocol until a well-powered
randomized controlled trial provides different insights.
PMID- 28424937
TI - Model to Predict Cause-Specific Mortality in Patients with Head and Neck Adenoid
Cystic Carcinoma: A Competing Risk Analysis.
AB - PURPOSE: The main objective of this study was to evaluate the cumulative
incidence of cause-specific death and other causes of death for patients with
head and neck adenoid cystic carcinoma (ACC). The secondary aim was to model the
probability of cause-specific death and build a competing risk nomogram to
predict cause-specific mortality for this disease. METHODS: Data were extracted
from the US National Cancer Institute's Surveillance Epidemiology, and End
Results (SEER)-18 dataset. The study cohort included patients with a diagnosis of
primary head and neck ACC during the period 2004-2013. We calculated the
cumulative incidence function (CIF) for cause-specific death and other causes of
death, and constructed the Fine and Gray's proportional subdistribution hazard
model, as well as a competing-risk nomogram based on Fine and Gray's model, to
predict the probability of cause-specific death for patients with head and neck
ACC. RESULTS: After data selection, 1435 cases were included for analysis. Five
year cumulative incidence of cause-specific death was 17.4% (95% confidence
interval [CI] 15.1-19.8%) and cumulative incidence of other causes of death was
5.8% (95% CI 4.4-7.4%). Predictors of cause-specific death for head and neck ACC
included age, tumor size, advanced T stage, positive lymph node, distant
metastasis, and surgery. The nomogram was well-calibrated, and had good
discriminative ability. CONCLUSION: The large sample allowed us to construct a
reliable predictive model for rare malignancy. The model performance was good,
with a concordance index of 0.79, and the nomogram can provide useful
individualized predictive information for patients with head and neck ACC.
PMID- 28424938
TI - Characterization and Genome Sequence of Marine Alteromonas gracilis Phage PB15
Isolated from the Yellow Sea, China.
AB - A novel marine Alteromonas gracilis siphovirus, phage PB15, was isolated from the
surface water of the Yellow Sea in August 2015. It has a head diameter of 58 +/-
5 nm head and a contractile tail approximately 105 +/- 10 nm in length, and
overall, the morphology suggests that PB15 belongs to the family Siphoviridae.
PB15 phage is stable at over the temperature range 0-60 degrees C. The best MOI
of these phage was 0.1, and infectivity decreased above 60 degrees C. The
results suggest that phage is stable at pH value ranging between 3.0 and 11.0.
Chloroform test shows that PB15 is not a lipid-containing phage. A one-step
growth curve with a strain of A. gracilis gave a latent period of 16 min and rise
period of 24 min and burst size of 60 PFU/cell. Genomic analysis of PB15 reveals
a genome size of 37,333 bp with 45.52% G+C content, and 61 ORFs. ORF sequences
accounted for 30.36% of the genome sequence. There is no obvious similarity
between PB15 and other known phages by genomic comparison using the BLASTN tool
in the NCBI database.
PMID- 28424939
TI - Characterization and Complete Genome Sequence of a Novel Siphoviridae
Bacteriophage BS5.
AB - A novel Siphoviridae family Phage BS5, which infects Pseudoalteromonas atlantica,
was isolated from the surface waters of the Yellow Sea. Morphological study by
transmission electron microscopy revealed that the novel phage belongs to
Siphoviridae. The complete genome sequence of PBS5 contained a linear, double
strand 39949-bp DNA molecule with a G + C content of 40.6% and 65 putative open
reading frames. Twelve conserved domains were detected by BLASTP in NCBI, and of
these the functions of 5 were known. The genome was grouped into four modules as
follows: phage structure, phage packaging, DNA replication and regulation, and
some additional functions.16 S rDNA sequence analysis was also applied to
identify the host bacteria. After initial characterization of bacteriophage PBS5,
it was found that the optimal pH was 7.0, the optimal temperature was 30 degrees
C, and the burst size was about 95 virions per cell. This information will
provide an important benchmark for further research on the interaction between
bacteriophages and their hosts.
PMID- 28424940
TI - Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of
Escherichia coli Mutants.
AB - Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has
become of great concern. The effect of some widely used food additives such as
sucralose on bacteria in the gut and the environment has also drawn increasing
attention. In this study, we investigated the interaction between antimicrobials
and sucralose impacting antimicrobial resistance and mutation of Escherichia coli
(E. coli). To examine antimicrobial resistance and mutation frequency, different
subinhibitory concentrations of sucralose were added to cultures of E.coli
BW25113 that were then treated with antimicrobials, oxolinic acid, or
moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of
mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of
E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose
increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of
sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72
h, while rifampicin-resistant mutation rate was increased when co-treated with
1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can
increase the antimicrobial resistance and mutation frequency of E.coli to some
antimicrobials.
PMID- 28424941
TI - Isolation and Complete Genome Sequence of a Novel Pseudoalteromonas Phage PH357
from the Yangtze River Estuary.
AB - Phage PH357, a novel lytic Pseudoalteromonas lipolytica phage belonging to the
Myoviridae family was isolated from the Yangtze River estuary. The
microbiological characterization demonstrated that phage PH357 is stable from -20
to 60 degrees C and the optimal pH 7. The one-step growth curve showed a latent
period of 20 min, a rise period of 20 min, and the average burst size was about
85 virions per cell. Complete genome of phage PH357 was determined. Genome of
phage PH357 consisted of a linear, double-stranded 136,203 bp DNA molecule with
34.58% G + C content, and 242 putative open reading frames (ORFs) without tRNA.
All the predicted ORFs were classified into eight functional groups, including
DNA replication, regulation and nucleotide metabolism, transcription,
translation, phage packaging, phage structure, lysis, host or phage interactions,
and hypothetical protein. A phylogenetic analysis showed that phage PH357 had
similarity to the previously published Pseudoalteromonas phage PH101 and Vibrio
phages. Furthermore, the study of phage PH357 genome will provide useful
information for further research on the interaction between phages and their
hosts.
PMID- 28424942
TI - Serratia bozhouensis sp. nov., Isolated from Sewage Samples of a Dairy Farm.
AB - A Gram-negative, rod-shaped, salt-tolerant, non-pigmented, and non-spore-forming
bacterium, designated strain W1T (type strain CICC 23797 = CGMCC1.14949), was
isolated from sewage samples of a dairy farm in Bozhou, Anhui, China. Strain W1
was resistant to lincomycin, troleandomycin, rifamycin, and vancomycin. Sequence
analysis of the 16S rDNA gene revealed that the strain showed sequence similarity
of 98.2% with the closest related species Serratia quinivorans CP6aT. The genomic
DNA G+C content of the isolate was 52.8 mol%. The biochemical characteristics of
strain W1T assessed by the API 20E and Biolog GEN III analysis were different
from those of the members of the genus Serratia. On the basis of the phenotypic
and genotypic differences, strain W1 was proposed to be a novel Serratia species,
Serratia bozhouensis sp. nov W1T.
PMID- 28424944
TI - Indirect interactions between arbuscular mycorrhizal fungi and Spodoptera exigua
alter photosynthesis and plant endogenous hormones.
AB - Peanut (Arachis hypogaea Linn. cv: Luhua 11) and tomato (Lycopersicon esculentum
Mill. cv: Zhongshu 4) were inoculated with arbuscular mycorrhizal fungi (AMF)
Funneliformis mosseae BEG167 (Fm), Rhizophagus intraradices BEG141 (Ri), and
Glomus versiforme Berch (Gv), and/or Spodoptera exigua (S. exigua) under
greenhouse conditions. Results indicated that feeding by S. exigua had little
influence on colonization of peanut plants by AMF, but improved colonization of
tomato by Fm and Gv. Feeding by S. exigua had little influence on leaf net
photosynthetic rate, transpiration rate, and stomatal conductance of
nonmycorrhizal peanut plants but significantly improved net photosynthetic rate
and transpiration rate of mycorrhizal plants of both hosts. AMF with or without
S. exigua inoculation improved host plant photosynthetic characteristics, growth,
and hormone status. Fm showed maximum beneficial effects, followed by Gv. The
concentrations and ratios of phytohormones abscisic acid (ABA), indole-3-acetic
acid (IAA), gibberellin (GA), zeatin riboside (ZR), and jasmonic acid (JA) in the
leaves of the host plants were changed due to the interaction between AMF and S.
exigua. Generally, AMF with or without S. exigua inoculation increased the
concentrations of GA, ZR, and JA and the ratios of IAA/ABA, GA/ABA, ZR/ABA, and
IAA + GA + ZR/ABA, while feeding by S. exigua on nonmycorrhizal plants showed the
opposite effect. The concentration of JA in the leaves of peanut and tomato
inoculated with Fm or Fm + S. exigua was 1.9 and 1.9 times and 2.5 and 2.7 times,
respectively, greater than that of the controls inoculated with neither. There
was a negative correlation between the JA concentration and the survival
percentage of S. exigua larva. We conclude that indirect interactions between AMF
and insect herbivores changed the photosynthetic and hormone characteristics, and
ratios of phytohormones, thereby revealing mechanisms of belowground-aboveground
interactions.
PMID- 28424943
TI - Intestinal Alkaline Phosphatase Attenuates Alcohol-Induced Hepatosteatosis in
Mice.
AB - BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role
in the activation of inflammatory pathways in the liver and in the pathogenesis
of alcoholic liver disease. The intestinal brush-border enzyme intestinal
alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory
factors and also functions to preserve gut barrier function. The aim of this
study was to investigate whether oral IAP supplementation could protect against
alcohol-induced liver disease. METHODS: Mice underwent acute binge or chronic
ethanol exposure to induce alcoholic liver injury and steatosis +/- IAP
supplementation. Liver tissue was assessed for biochemical, inflammatory, and
histopathological changes. An ex vivo co-culture system was used to examine the
effects of alcohol and IAP treatment in regard to the activation of hepatic
stellate cells and their role in the development of alcoholic liver disease.
RESULTS: Pretreatment with IAP resulted in significantly lower serum alanine
aminotransferase compared to the ethanol alone group in the acute binge model.
IAP treatment attenuated the development of alcohol-induced fatty liver, lowered
hepatic pro-inflammatory cytokine and serum LPS levels, and prevented alcohol
induced gut barrier dysfunction. Finally, IAP ameliorated the activation of
hepatic stellate cells and prevented their lipogenic effect on hepatocytes.
CONCLUSIONS: IAP treatment protected mice from alcohol-induced hepatotoxicity and
steatosis. Oral IAP supplementation could represent a novel therapy to prevent
alcoholic-related liver disease in humans.
PMID- 28424945
TI - Date palm waste biochars alter a soil respiration, microbial biomass carbon, and
heavy metal mobility in contaminated mined soil.
AB - A 30-day incubation experiment was conducted using a heavy metal-contaminated
mined soil amended with date palm feedstock (FS) and its derivative biochars
(BCs) at three pyrolysis temperatures of 300 (BC-300), 500 (BC-500), and 700
degrees C (BC-700) with different application rates (0.0, 5, 15, and 30 g kg-1)
to investigate their short-term effects on soil respiration (CO2-C efflux),
microbial biomass carbon (MBC), soil organic carbon (SOC), mobile fraction of
heavy metals (Cd, Cu, Pb, Zn, Mn, and Fe), pH, and electrical conductivity (EC).
The results showed that FS and BC-300 with increasing addition rate significantly
reduced soil pH, whereas SOC, CO2-C efflux, and soil MBC were increased compared
to the control. On the contrary, BC-500 and BC-700 increased soil pH at early
stage of incubation and have small or no effects on SOC, CO2-C efflux, and MBC.
Based on the results, the date palm biochars exhibited much lower cumulative CO2
C efflux than feedstock, even with low-temperature biochar, indicating that BCs
have C sequestration potential. Applying BC-700 at 15 and 30 g kg-1 significantly
reduced cumulative CO2-C efflux by 21.8 and 45.4% compared to the control,
respectively. The incorporation of FS into contaminated soil significantly
increased the mobile content of Cd and Mn, but decreased the mobile content of
Cu. However, BC-300 significantly reduced the mobile content of Cd, Cu, Pb, and
Zn. It could be concluded that low-temperature biochar could be used as a soil
amendment for reducing heavy metal mobility in mining contaminated soil in
addition to minimize soil CO2-C efflux.
PMID- 28424946
TI - Preparation and corrosion resistance of magnesium phytic acid/hydroxyapatite
composite coatings on biodegradable AZ31 magnesium alloy.
AB - In this work, a magnesium phytic acid/hydroxyapatite composite coating was
successfully prepared on AZ31 magnesium alloy substrate by chemical conversion
deposition technology with the aim of improving its corrosion resistance and
bioactivity. The influence of hydroxyapatite (HA) content on the microstructure
and corrosion resistance of the coatings was investigated. The results showed
that with the increase of HA content in phytic acid solution, the cracks on the
surface of the coatings gradually reduced, which subsequently improved the
corrosion resistance of these coated magnesium alloy. Electrochemical
measurements in simulated body fluid (SBF) revealed that the composite coating
with 45 wt.% HA addition exhibited superior surface integrity and significantly
improved corrosion resistance compared with the single phytic acid conversion
coating. The results of the immersion test in SBF showed that the composite
coating could provide more effective protection for magnesium alloy substrate
than that of the single phytic acid coating and showed good bioactivity.
Magnesium phytic acid/hydroxyapatite composite, with the desired bioactivity, can
be synthesized through chemical conversion deposition technology as protective
coatings for surface modification of the biodegradable magnesium alloy implants.
The design idea of the new type of biomaterial is belong to the concept of "third
generation biomaterial". Corrosion behavior and bioactivity of coated magnesium
alloy are the key issues during implantation. In this study, preparation and
corrosion behavior of magnesium phytic acid/hydroxyapatite composite coatings on
magnesium alloy were studied. The basic findings and significance of this paper
are as follows: 1. A novel environmentally friendly, homogenous and crack-free
magnesium phytic acid/hydroxyapatite composite coating was fabricated on AZ31
magnesium alloy via chemical conversion deposition technology with the aim of
enhancing its corrosion resistance and bioactivity. The chemical conversion
coatings, which are formed through the reaction between the substrate and the
environment, have attracted increasing attention owing to the relative low
treatment temperature, favorable bonding to substrate and simple implementation
process. 2. With the increasing of hydroxyapatite (HA) content, the crack width
in the composite coatings and the thickness of the coatings exhibit obviously
decreased. The reason is probably that when adding HA into the phytic acid
solution, the amount of active hydroxyl groups in the phytic acid are reduced via
forming the coordination bond between P-OH groups from phytic acid and P-OH
groups from the surface of HA, thus decreasing the coating thickness and hydrogen
formation, as well as avoiding coating cracking. 3. By adjusting the HA content
to 45 wt.%, a dense and relatively smooth composite coating with ~1.4 MUm
thickness is obtained on magnesium alloy, and exhibits high corrosion resistance
and good bioactivity when compared with the single phytic acid conversion
coating.
PMID- 28424947
TI - Neurodevelopmental Effects of Antiepileptic Drugs.
AB - Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs)
during critical periods of development may induce transient or long-lasting
neurodevelopmental deficits across cognitive, motor and behavioral domains. The
developing nervous system may endure prolonged chronic exposure to AEDs during
pregnancy (in utero) or during childhood, which can lead to neurodevelopmental
defects such as congenital neural tube defects, lower IQ, language deficits,
autism and ADHD. To date, valproate is the most widely recognized AED to
significantly negatively affect neurodevelopment, and demonstrates greater
adverse effects than any other AEDs that have been assessed. Although some AEDs
appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been
implicated in a variety of studies detailed below, and many AEDs have not been
adequately assessed. The purpose of this review article is to summarize our
current understanding of the neurodevelopmental effects of AEDs.
PMID- 28424948
TI - 14-3-3 Isoforms Differentially Regulate NFkappaB Signaling in the Brain After
Ischemia-Reperfusion.
AB - Mammalian 14-3-3 isoforms exist predominantly in the brain and are heavily
involved in neurological diseases. However, the isoform-specific role of 14-3-3
proteins in the brain remains largely unclear. Here, we investigated the role of
14-3-3 isoforms in rat brains after transient middle cerebral artery occlusion
and reperfusion. 14-3-3beta, eta, gamma and zeta but not epsilon or tau were
selectively upregulated in cerebral cortical neurons after ischemia-reperfusion
(I/R). Selectively, 14-3-3beta, gamma and zeta were translocated from cytoplasm
into the nuclei of neurons after I/R. 14-3-3 bound to p65 and suppressed p65
expression in N2a cells. In the brain, 14-3-3 could either colocalize with p65 in
the nuclei of neurons or segregate from p65 expression in cortical neurons after
I/R. All evidence together suggests that 14-3-3 isoforms are differentially
induced to enter into the nuclei of neurons after I/R, which might regulate
NFkappaB signaling directly or indirectly. Since 14-3-3 proteins are essential
for cell survival and NFkappaB is a key transcriptional factor, our data suggest
that the 14-3-3/p65 signaling pathway might be a potential therapeutic target for
stroke.
PMID- 28424950
TI - Estimated work ability in warm outdoor environments depends on the chosen heat
stress assessment metric.
AB - With a view to occupational effects of climate change, we performed a simulation
study on the influence of different heat stress assessment metrics on estimated
workability (WA) of labour in warm outdoor environments. Whole-day shifts with
varying workloads were simulated using as input meteorological records for the
hottest month from four cities with prevailing hot (Dallas, New Delhi) or warm
humid conditions (Managua, Osaka), respectively. In addition, we considered the
effects of adaptive strategies like shielding against solar radiation and
different work-rest schedules assuming an acclimated person wearing light work
clothes (0.6 clo). We assessed WA according to Wet Bulb Globe Temperature (WBGT)
by means of an empirical relation of worker performance from field studies
(Hothaps), and as allowed work hours using safety threshold limits proposed by
the corresponding standards. Using the physiological models Predicted Heat Strain
(PHS) and Universal Thermal Climate Index (UTCI)-Fiala, we calculated WA as the
percentage of working hours with body core temperature and cumulated sweat loss
below standard limits (38 degrees C and 7.5% of body weight, respectively)
recommended by ISO 7933 and below conservative (38 degrees C; 3%) and liberal
(38.2 degrees C; 7.5%) limits in comparison. ANOVA results showed that the
different metrics, workload, time of day and climate type determined the largest
part of WA variance. WBGT-based metrics were highly correlated and indicated
slightly more constrained WA for moderate workload, but were less restrictive
with high workload and for afternoon work hours compared to PHS and UTCI-Fiala.
Though PHS showed unrealistic dynamic responses to rest from work compared to
UTCI-Fiala, differences in WA assessed by the physiological models largely
depended on the applied limit criteria. In conclusion, our study showed that the
choice of the heat stress assessment metric impacts notably on the estimated WA.
Whereas PHS and UTCI-Fiala can account for cumulative physiological strain
imposed by extended work hours when working heavily under high heat stress, the
current WBGT standards do not include this. Advanced thermophysiological models
might help developing alternatives, where not only modelling details but also the
choice of physiological limit criteria will require attention. There is also an
urgent need for suitable empirical data relating workplace heat exposure to
workability.
PMID- 28424949
TI - Aggressive Crosstalk Between Fatty Acids and Inflammation in Macrophages and
Their Influence on Metabolic Homeostasis.
AB - From the immunological point of view, macrophages are required to maintain
metabolic homeostasis. Recently, there has been an increased focus on the
influence of macrophage phenotypes in adipose tissue on the maintenance of
metabolic homeostasis in healthy conditions because dysregulated metabolic
homeostasis causes metabolic syndrome. This review notes several types of
inflammatory and anti-inflammatory mediators in metabolic homeostasis. M1
macrophage polarization mediates inflammation, whereas M2 macrophage polarization
mediates anti-inflammation. Fatty acids and their related factors mediate both
inflammatory and anti-inflammatory responses. Saturated fatty acids and
polyunsaturated fatty acids mediate inflammation, whereas marine-derived n-3
fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, mediate anti
inflammation. In this review, we discuss the current understanding of the
crosstalk between fatty acids and inflammation in macrophages and their influence
on metabolic homeostasis.
PMID- 28424951
TI - Influence of Genetic Counseling Graduate Program Websites on Student Application
Decisions.
AB - This study investigated how genetic counseling educational program websites
affect application decisions via an online survey sent to current students and
recent graduates. Program leadership: directors, assistant directors, associate
directors, were also surveyed to determine where their opinions coincided or
differed from those reported by students and recent graduates. Chi square
analysis and t-tests were used to determine significance of results. A two-sample
t-test was used to compare factors students identified as important on a 5-point
Likert scale with those identified by directors. Thematic analysis revealed three
major themes students consider important for program websites: easy navigation,
website content, and website impression. Directors were interested in how
prospective students use their program website and what information they found
most useful. Students indicated there were specific programs they chose not to
apply to due to the difficulty of using the website for that program. Directors
significantly underestimated how important information about application
requirements was to students in making application decisions. The information
reported herein will help individual genetic counseling graduate programs improve
website functionality and retain interested applicants.
PMID- 28424952
TI - Preadolescents' Emotional and Prosocial Responses to Negative TV News:
Investigating the Beneficial Effects of Constructive Reporting and Peer
Discussion.
AB - Watching news is important for preadolescents, but it may also harm their well
being. This study examined whether applying insights from positive psychology to
news production can reduce this potential harm, by reducing negative emotional
responses and enhancing positive emotional responses to negative news, and by
encouraging prosocial intentions. Moreover, we explored whether peer discussion
strengthened these effects. Preadolescents (n = 336; 9-13 years old; 48.5%
female) were exposed to either constructive (solution-based news including
positive emotions) or nonconstructive news. Subsequently, half of the children
assigned to the constructive and the nonconstructive condition participated in a
peer discussion. The findings showed that exposure to constructive news resulted
in more positive emotional responses and less negative emotional responses as
compared to nonconstructive news. Moreover, discussing the news with peers led to
more positive and less negative emotional responses among preadolescents who
watched the nonconstructive newscast, and to more prosocial intentions among
preadolescents who watched constructive news. In all, constructive news reporting
and peer discussion could function as tools to make negative news less harmful
for preadolescents.
PMID- 28424954
TI - Trendiness in human ARTs as technology transits from the macro to nano.
PMID- 28424955
TI - Erratum to: Study of plasma off-gas treatment from spent ion exchange resin
pyrolysis.
PMID- 28424953
TI - Treatment Update of Chronic Migraine.
AB - PURPOSE OF REVIEW: Although chronic migraine (CM) is a common disorder that
severely impacts patient functioning and quality of life, it is usually
underdiagnosed, and treatment responses often remain poor even after diagnosis.
In addition, effective treatment options are limited due to the rarity of
randomized controlled trials (RCTs) involving patients with CM. In the present
review, we discuss updated pharmacological, non-pharmacological, and
neurostimulation treatment options for CM. RECENT FINDINGS: Pharmacological
treatments include both acute and preventive measures. While acute treatment
options are similar between CM and episodic migraine (EM), preventive treatment
with topiramate and botulinum toxin A exhibited efficacy in more than two RCTs.
In addition, several studies have revealed that behavioral interventions such as
cognitive behavioral therapy, biofeedback, and relaxation techniques are
associated with significant improvements in symptoms. Thus, these treatment
options are recommended for patients with CM, especially for refractory cases.
Neurostimulation procedures, such as occipital stimulation, supraorbital
transcutaneous stimulation, non-invasive vagal nerve stimulation, and
transcranial direct current stimulation, have shown promising results in the
treatment of CM. However, current studies on neurostimulation suffer from small
sample size, no replication, or negative results. Although CM is less responsive
to treatment compared to EM, recent advance in pharmacological, non
pharmacological, and neurostimulation treatments may provide more chance for
successful treatment of CM.
PMID- 28424956
TI - Removal of selected pesticides from groundwater by membrane distillation.
AB - The removal of five selected pesticide compounds in a brackish model groundwater
solution was examined using a bench scale direct contact membrane distillation
(DCMD) system. It was found that the rejection rate of the pesticides in DCMD is
mainly influenced by its properties. Compounds with low hydrophobic
characteristics and low vapour pressure showed a high rejection rate (70-99%),
whereas compounds with a high vapour pressure or high hydrophobicity (LogD)
showed a reduced rejection (30-50%) at a water recovery of 75%. The influence of
groundwater feed solution contents such as the presence of organics (humic acid)
and inorganic ions (Na+, Ca2+, Mg2+, Cl- and SO42-) as well as feed temperature
(40, 55 and 70 degrees C) on the rejection of the pesticides in DCMD operation
was also evaluated. The results showed that the presence of inorganic ions and
organics in the feed solution influences the pesticides rejection in DCMD
operation to a minor degree. In contrast, reduced rejection of pesticides with
high vapour pressure was observed. A rapid small-scale column test (RSSCT) was
carried out to study the removal of any remaining substances in the permeate by
adsorption onto granular activated carbon (GAC). RSSCT showed promising
performance of GAC as a post-treatment option.
PMID- 28424957
TI - Assessing PAHs pollution in Shandong coastal area (China) by combination of
chemical analysis and responses of reproductive toxicity in crab Portunus
trituberculatus.
AB - The concentrations of PAHs in seawater and sediments were measured at three
selected sites (S1, S2, and S3) along the coastal area of Shandong (China) in
April, May, and June, 2015, which ranged from 29.72 to 123.88 ng/L and 82.62 to
232.63 ng/g, respectively. Meanwhile, the reproductive toxicity responses in crab
Portunus trituberculatus were also evaluated to assess the pollution of PAHs
during the sampling period. Chemical analysis showed that S3 was the most PAH
contaminated area while S1 was the least, and the biochemical parameters
concerned with reproduction were efficiently responded to the three sites,
especially in S3 (p < 0.05). Moreover, the principal component analyses (PCA)
showed that parameters for DNA alkaline unwinding, protein carbonyl content, and
lipid peroxidation levels in two genders, 17beta-estradiol in female,
testosterone and TESK2 gene expression in male crabs, were closely correlated
with the concentrations of PAHs (2 + 3 rings, 4 rings, and 5 + 6 rings), which
were considered to be good candidate indicators to assess the environmental
pollutions resulting from PAHs in the coastal area of Shandong, China.
PMID- 28424958
TI - Effectiveness of waste prevention program in primary students' schools.
AB - Even though reducing waste is at the top of the waste hierarchy, no real
decoupling between waste generation and consumption has been demonstrated.
Several waste directives had been published from EU, but they have only brought
minor changes within the key objective of reducing waste generation. Most efforts
have been targeted towards greater amounts of recycling and better management of
waste disposal. While these are necessary and socially beneficial goals, they are
not adequate for the achievement of long-term sustainability goals. The purpose
of this study is to understand students' knowledge, attitudes and behavioural
changes in relation to the water plastic bottle of 500 ml. Understanding waste
prevention behaviour (WPB) could enable schools' principals, local authorities
and committees as well as decision makers to design and implement more effective
policies for reducing the amount of specific waste streams that is generated.
Students in a daily base bring their own water containers of 500 ml or buy water
from the school as they do not feel safe to use other sources of water. Nine
hundred ninety-eight refilling stainless steel water refilling bottles (SSWRB-of
600 ml) were shared to the students in four primary schools. The results
indicated that the students are presented with different behaviours from class to
class for many reasons; most of them are related with what their parents believe,
and how themselves or the synergies between them reacts and affected.
PMID- 28424959
TI - Non-essential element concentrations in brown grain rice: Assessment by advanced
data mining techniques.
AB - The concentrations of 17 non-essential elements (Al, As, Ba, Be, Cd, Ce, Cr, Hg,
La, Li, Pb, Sb, Sn, Sr, Th, Ti, and Tl) were determined in brown grain rice
samples of two varieties: Fortuna and Largo Fino. The samples were collected from
the four main producing regions of Corrientes province (Argentina). Quantitative
determinations were performed by inductively coupled plasma mass spectrometry
(ICP-MS), using a validated method. The contents of As, Be, Cd, Ce, Cr, Hg, Pb,
Sb, Sn, Th, and Tl were very low or not detected in most samples. The non
essential element levels detected were in line with studies conducted in rice
from different parts of the world. In order to characterize the influence of
geographical origin in the samples, the following classification methods were
carried out: linear discriminant analysis (LDA), k-nearest neighbors (k-NN),
partial least squares discriminant analysis (PLS-DA), support vector machine
(SVM) and random forests (RF). The best performance was obtained by using RF
(96%) and SVM (96%). The results reported here showed the variation in the non
essential element profiles in rice grain depending on the geographical origin.
PMID- 28424960
TI - Selenium for the mitigation of toxicity induced by lead in chicken testes through
regulating mRNA expressions of HSPs and selenoproteins.
AB - Lead (Pb) is a toxic element and environmental pollutant. Pb toxicity and
antagonistic effect of selenium (Se) on Pb have been deeply studied in mammals.
The testis is one of the target organs of Pb in birds. The aim of this study was
to investigate the mitigating effect of Se on Pb toxicity in chicken testes by
determining messenger RNA (mRNA) expressions of 5 heat shock proteins (HSPs) and
25 selenoproteins. Sixty male chickens (7-day-old) were randomly divided into the
control group, the Se group, the Pb group, and the Pb + Se group, and were fed
for 90 days. The feeding methods of chickens were as follows: The control group
was fed drinking water and commercial diet (0.49 mg/kg Se). Lead acetate was
added into the drinking water (350 mg/L Pb). Sodium selenite was added into the
commercial diet (1 mg/kg Se). Multivariate correlation analysis and principal
component analysis (PCA) were used to define the relationships among all the
measured factors and the most important parameters that could be used as key
factors, respectively. The results indicated that Se decreased the increase of
mRNA expressions of all the HSPs and increased the decrease of mRNA expressions
of all the selenoproteins induced by Pb in the chicken testes. HSP70 may be a
biomarker of Pb poisoning in the chicken testes. Se alleviated Pb-induced
toxicity in the chicken testes through regulating mRNA expressions of HSPs and
selenoproteins.
PMID- 28424961
TI - Tillandsia usneoides: A successful alternative for biomonitoring changes in air
quality due to a new highway in Sao Paulo, Brazil.
AB - Tillandsia usneoides is an aerial epiphytic bromeliad that absorbs water and
nutrients directly from the atmosphere by scales covering its surface. We
expanded the use of this species as a broader biomonitor based on chemical and
structural markers to detect changes in air quality. The usefulness of such
comprehensive approach was tested during the construction and opening of a
highway (SP-21) in Sao Paulo State, Brazil. The biomonitoring study was performed
from 2009 to 2012, thus comprising the period during construction and after the
highway inauguration. Metal accumulation and structural alterations were
assessed, in addition to microscopy analyses to understand the metal chelation in
plant tissues and to assess the causes of alterations in the number and shape of
scale cells. Altogether, our analyses support the use of this species as a wide
biomonitor of air quality in urbanized areas.
PMID- 28424962
TI - Phase I dose-escalation study of milciclib in combination with gemcitabine in
patients with refractory solid tumors.
AB - BACKGROUND: This phase I trial evaluated the safety and tolerability of
milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin
receptor kinase A, in combination with gemcitabine in patients with refractory
solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib
at three dose levels (45 mg/m2/day, n = 3; 60 mg/m2/day, n = 3; and 80 mg/m2/day,
n = 10) with a fixed dose of gemcitabine (1000 mg/m2/day). Milciclib was
administered orally once daily for 7 days on/7 days off in a 4-week cycle, and
gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle.
RESULTS: All 16 enrolled patients were evaluable for safety and toxicity. Dose
limiting toxicities, which occurred in only one out of nine patients treated at
the maximum dose tested (milciclib 80 mg/m2/day and gemcitabine 1000 mg/m2/day),
consisted of Grade 4 thrombocytopenia, Grade 3 ataxia and Grade 2 tremors in the
same patient. Most frequent treatment-related AEs were neutropenia and
thrombocytopenia. Among 14 evaluable patients, one NSCLC patient showed partial
response and 4 patients (one each with thyroid, prostatic, pancreatic carcinoma
and peritoneal mesothelioma) showed long-term disease stabilization (>6-14
months). Pharmacokinetics of the orally administered milciclib (~t1/2 33 h) was
not altered by concomitant treatment with gemcitabine. CONCLUSION: The
combination treatment was well tolerated with manageable toxicities. The
recommended phase II dose was 80 mg/m2/day for milciclib and 1000 mg/m2/day for
gemcitabine. This combination treatment regimen showed encouraging clinical
benefit in ~36% patients, including gemcitabine refractory patients. These
results support further development of combination therapies with milciclib in
advanced cancer patients.
PMID- 28424963
TI - Pharmacokinetics and safety of carfilzomib in patients with relapsed multiple
myeloma and end-stage renal disease (ESRD): an open-label, single-arm, phase I
study.
AB - PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in
multiple myeloma patients with varying degrees of renal impairment (normal, mild,
moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20
mg/m2. This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m2 in
normal renal function and ESRD patients. METHODS: Patients received carfilzomib
on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m2 (cycle 1
day 1-2), escalated to 27 mg/m2 on cycle 1 day 8; if tolerated, 56 mg/m2 starting
cycle 2 day 1. The primary objective was PK assessment with safety/tolerability
and response rate as secondary and exploratory objectives, respectively. RESULTS:
26 patients were enrolled (15 normal, 11 ESRD). There was a trend toward higher
area under the concentration time curve (AUC) and maximum concentration in ESRD
versus normal renal function patients; however, high interpatient PK variability
was discerned. Relative to patients with normal renal function, ESRD patients
showed 33% higher AUC. Overall response rate was 43% for the normal renal
function and 60% for the ESRD groups. Safety findings were generally similar
between the two groups and consistent with the known safety profile of
carfilzomib in multiple myeloma patients. CONCLUSION: There were no meaningful
differences in PK between patients with normal renal function and ESRD in light
of carfilzomib exposure-response relationships. These results continue to support
dosing recommendation that no starting dose adjustment of carfilzomib appears
warranted in patients with baseline renal impairment.
PMID- 28424964
TI - Pharmacodynamic effects in the cerebrospinal fluid of rats after intravenous
administration of different asparaginase formulations.
AB - PURPOSE: Asparaginase (ASNase) is used to treat various hematological
malignancies for its capacity to deplete asparagine (ASN) in serum and
cerebrospinal fluid (CSF). Since the biological mechanisms underlying CSF
asparagine depletion in humans are not yet fully elucidated, this study compared,
for the first time, the pharmacological properties of three clinically used
ASNase formulations in a rodent model. METHODS: Male Wistar rats were treated
with E.coli-ASNase, PEG-ASNase, or ERW-ASNase at different doses. Serum and CSF
amino-acid levels and ASNase activities were evaluated at 1 and 24 h after the
intravenous administration of different ASNase doses. RESULTS: All the ASNase
formulations showed higher activities in serum after 1 h than 24 h and completely
deplete ASN. Mean ASNase activity in the CSF at 1 h was higher with ERW-ASNase
compared to PEG-ASNase (36 +/- 29 vs 8 +/- 7 U/L, p < 0.037) and similar to
E.coli-ASNase (21 +/- 9 U/L, ns). ERW-ASNase and E.coli-ASNase at the highest
doses were able to deplete ASN in the CSF after 1 h. This effect was transient
and not evident at 24 h after treatment. CONCLUSIONS: Together with the ASN
depletion in serum and CSF, a never before demonstrated transient penetration of
ASNases into the CSF, more evident for non-pegylated formulations, was detected
when the ASNases were administered at high dose.
PMID- 28424965
TI - Assessment of drug-drug interaction potential between ceritinib and proton pump
inhibitors in healthy subjects and in patients with ALK-positive non-small cell
lung cancer.
AB - PURPOSE: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK)
and efficacy of ceritinib was evaluated. METHODS: A healthy subject drug-drug
interaction (DDI) study was conducted to assess the effect of esomeprazole on the
PK of a single 750 mg dose of ceritinib. To further investigate the impact of
PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two
subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state
trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant
use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2
evaluated ceritinib single-dose and steady-state AUC0-24h and C max by
concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage
similar to that used in the healthy subject study. RESULTS: In the healthy
subject study, co-administration of a single 750 mg dose of ceritinib with
esomeprazole 40 mg for 6 days decreased ceritinib AUC0-infinity by 76% and C max
by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss
and ORR regardless of concomitant PPI usage. Based on analysis 2, co
administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients
suggested less effect on ceritinib exposure than that observed in healthy
subjects as AUC0-24h decreased by 30% and C max decreased by 25%. No clinically
meaningful effect on steady-state exposure was observed after daily dosing.
CONCLUSIONS: Long-term administration of ceritinib with PPIs does not adversely
affect the PK and efficacy of ceritinib in ALK-positive cancer patients.
PMID- 28424966
TI - Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots
affected by apple replant disease.
AB - KEY MESSAGE: Gene expression studies in roots of apple replant disease affected
plants suggested defense reactions towards biotic stress to occur which did not
lead to adequate responses to the biotic stressors. Apple replant disease (ARD)
leads to growth inhibition and fruit yield reduction in replanted populations and
results in economic losses for tree nurseries and fruit producers. The etiology
is not well understood on a molecular level and causal agents show a great
diversity indicating that no definitive cause, which applies to the majority of
cases, has been found out yet. Hence, it is pivotal to gain a better
understanding of the molecular and physiological reactions of the plant when
affected by ARD and later to overcome the disease, for example by developing
tolerant rootstocks. For the first time, gene expression was investigated in
roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and
RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as
plant defense, regulatory and signaling genes were upregulated whereas for
several genes involved in primary metabolism lower expression was detected. For
internal verification of MACE data, candidate genes were tested via RT-qPCR and a
strong positive correlation between both datasets was observed. Comparison of
apple 'M26' roots cultivated in ARD soil or gamma-irradiated ARD soil suggests
that typical defense reactions towards biotic stress take place in ARD affected
plants but they did not allow responding to the biotic stressors attack
adequately, leading to the observed growth depressions in ARD variants.
PMID- 28424967
TI - Disparities of Selected Metal Levels in the Blood and Scalp Hair of Ischemia
Heart Disease Patients and Healthy Subjects.
AB - Imbalances in the concentrations of trace metals have become an increasingly
recognized source of infirmity worldwide particularly in the development of
ischemia heart disease (IHD). Present study is intended to analyze the
concentrations of Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Pb, Sr, and Zn in
the blood and scalp hair of the patients and counterpart controls by flame atomic
absorption spectrometry after wet-acid digestion. On the average, Cd, Co, Cr, Fe,
K, Li, Mn, Na, and Pb revealed significantly elevated concentrations in the blood
of the patients compared with the controls (p < 0.05), whereas mean levels of Ca,
Cd, Fe, K, Li, Pb, and Sr in the scalp hair were significantly higher in the
patients than the controls (p < 0.05). Most of the metals exhibited noticeable
disparities in their concentrations based on gender, abode, dietary/smoking
habits, and occupations of both donor groups. The correlation study and
multivariate statistical analyses revealed some significantly divergent
associations and apportionment of the metals in both donor groups. Overall,
comparative variations of the metal contents in blood/scalp hair of the patients
were significantly different than the controls; thus, evaluation of trace metals
status may be indicative of pathological disorders, such as IHD.
PMID- 28424968
TI - Visualization of reticulophagy in living cells using an endoplasmic reticulum
targeted p62 mutant.
AB - Reticulophagy is a type of selective autophagy in which protein aggregate
containing and/or damaged endoplasmic reticulum (ER) fragments are engulfed for
lysosomal degradation, which is important for ER homeostasis. Several chemical
drugs and mutant proteins that promote protein aggregate formation within the ER
lumen can efficiently induce reticulophagy in mammalian cells. However, the exact
mechanism and cellular localization of reticulophagy remain unclear. In this
report, we took advantage of the self-oligomerization property of p62/SQSTM1, an
adaptor for selective autophagy, and developed a novel reticulophagy system based
on an ER-targeted p62 mutant to investigate the process of reticulophagy in
living cells. LC3 conversion analysis via western blot suggested that p62 mutant
aggregate-induced ER stress triggered a cellular autophagic response. Confocal
imaging showed that in cells with moderate aggregation conditions, the aggregates
of ER-targeted p62 mutants were efficiently sequestered by autophagosomes, which
was characterized by colocalization with the autophagosome precursor marker
ATG16L1, the omegasome marker DFCP1, and the late autophagosomal marker LC3/GATE
16. Moreover, time-lapse imaging data demonstrated that the LC3- or DFCP1
positive protein aggregates are tightly associated with the reticular structures
of the ER, thereby suggesting that reticulophagy occurs at the ER and that
omegasomes may be involved in this process.
PMID- 28424969
TI - Values and limitations of the comparing thyroid radiofrequency and microwave
ablation using propensity score.
PMID- 28424970
TI - Neighborhood Environments and Sexual Risk Behaviors for HIV Infection Among U.S.
Women: A Systematic Review.
AB - Empirical evidence indicates that aspects of the neighborhood environment may
affect HIV prevention efforts. Therefore, the neighborhood environment should be
considered when implementing prevention interventions. However, much of the
empirical evidence is derived from studies conducted among drug users, men, or
adolescents. Such evidence may not be as applicable to adult women whose primary
risk for HIV infection is via heterosexual sexual behavior. Therefore, a
systematic review examining the relationship between neighborhood environments
and HIV sexual risk behaviors among adult U.S. women was conducted. Three
databases were searched for articles published in English in peer-reviewed
journals between 1/1/1980 and 12/31/2016 meeting relevant criteria. Seven
articles identified from the three databases or additional hand searches met
inclusion criteria and were summarized. Findings were mixed with several studies
indicating associations between neighborhood environments and HIV sexual risk
behaviors. However, all summarized studies were cross-sectional. Longitudinal
studies conducted among women are needed.
PMID- 28424971
TI - High Frequency of Illegal Drug Use Influences Condom Use Among Female Transgender
Sex Workers in Argentina: Impact on HIV and Syphilis Infections.
AB - The high prevalence of HIV and syphilis found among female transgender sex
workers (FTSWs) in Argentina calls for the study of factors leading to negative
health consequences. Given the particular characteristics observed in this
population (high marginalization, school dropout, and low adherence to healthcare
services), we explored the association of several socio-demographic
characteristics with syphilis and HIV infections, and the determinants of condom
use. This study revealed that FTSWs from Argentina were exposed to several risk
factors decreasing thus their ability to negotiate condom use and leading to
increased risk for transmission of HIV and other sexually transmitted infections
(STIs). Strategies to reduce HIV and syphilis in this population should consider
interventions aimed at decreasing violence and substance use which appear to be
the most important determinants. Results of this study will contribute to the
global information among FTSWs.
PMID- 28424972
TI - Biosimilars in the United States: Emerging Issues in Litigation.
AB - Many first-generation biologics will lose their patent protection by 2020. The
biosimilars market is not only attractive but also competitive and tough. The
United States (US) is the world's largest pharmaceutical market and is critical
to the success of most drugs. However, unclear regulatory requirements and
confusing patent resolution procedures create hurdles to market entry of
biosimilars. Trade secret exposure and scant exclusivity and adoption also limit
the market access of biosimilars. Both biologics and biosimilar developers should
closely follow the regulatory and litigation landscape to successfully navigate
through the challenges. Focusing on the US landscape, this article provides a
brief review of the regulatory framework for biosimilar products, market
exclusivities, and patent issues under the Biologics Price Control and Innovation
Act (BPCIA), analyzes emerging issues in the biosimilar litigation landscape, and
provides recommendations for companies entering the biosimilars market.
PMID- 28424973
TI - PCSK9 Inhibitors in Hyperlipidemia: Current Status and Clinical Outlook.
AB - The clinical reality of residual risk despite statin (HMG-CoA reductase
inhibitor) therapy and emergence of statin intolerance support the need to
develop additional lipid-lowering strategies. Proprotein convertase subtilisin
kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and
clinical studies that have revealed its pivotal role in the regulation of
cholesterol homeostasis. Monoclonal antibodies have been developed targeting
PCSK9, which have been demonstrated to produce profound low-density lipoprotein
cholesterol (LDL-C) lowering when provided as monotherapy or in combination with
statins. With the reports that the PCSK9 inhibitor evolocumab has a favorable
impact on both plaque progression and cardiovascular outcomes, these findings
begin to translate the benefits of PCSK9 inhibition from lipids to the vessel
wall and ultimately to clinical outcomes. The clinical implications for the use
of these agents are reviewed in this article.
PMID- 28424974
TI - Transposable elements in the Anopheles funestus transcriptome.
AB - Transposable elements (TEs) are present in most of the eukaryotic genomes and
their impact on genome evolution is increasingly recognized. Although there is
extensive information on the TEs present in several eukaryotic genomes, less is
known about the expression of these elements at the transcriptome level. Here we
present a detailed analysis regarding the expression of TEs in Anopheles
funestus, the second most important vector of human malaria in Africa. Several
transcriptionally active TE families belonging both to Class I and II were
identified and characterized. Interestingly, we have identified a full-length
putative active element (including the presence of full length TIRs in the
genomic sequence) belonging to the hAT superfamily, which presents active members
in other insect genomes. This work contributes to a comprehensive understanding
of the landscape of transposable elements in A. funestus transcriptome. Our
results reveal that TEs are abundant and diverse in the mosquito and that most of
the TE families found in the genome are represented in the mosquito
transcriptome, a fact that could indicate activity of these elements.The vast
diversity of TEs expressed in A. funestus suggests that there is ongoing
amplification of several families in this organism.
PMID- 28424975
TI - ETV-2 activated proliferation of endothelial cells and attenuated acute hindlimb
ischemia in mice.
AB - Ischemia is the reduction of blood flow to tissues by injury of blood vessels.
Depending on the sites of tissues and grade of ischemia, ischemia can cause many
serious complications. This study aimed to evaluate the effects of the E-twenty
six (ETS) factor Ets variant 2 (ETV2) gene expression in angiogenesis and the
effect of ETV2 gene therapy in a mouse model of hindlimb ischemia. The role of
ETV2 on endothelial cell proliferation was evaluated in vitro. Knockdown of ETV2
expression was done using short hairpin RNA (shRNA) lentiviral viral particles.
The ETV2 viral vector was injected into the skeletal muscles at the ligated and
burned sites of the hindlimb and evaluated for its efficacy as a gene therapy
modality for ischemia. Vascular regeneration in mice was indirectly evaluated by
changes in mouse survival, necrotic grades of the leg, normal blood oxygen
saturation level (SpO2), and blood flow by trypan blue injection assay.
Preliminary data showed that ETV2 expression played a role in angiogenesis of
endothelial cells. ETV2 overexpression could trigger and stimulate proliferation
of skeletal endothelial cells. In vivo knockdown of ETV2 expression inhibited the
auto-recovery of ischemic hindlimb, while overexpression of ETV2 helped to rescue
leg loss and reduce necrosis, significantly improving angiogenesis in hindlimb
ischemia. Our findings demonstrate that ETV2 gene therapy is a potentially
effective modality for vascular regeneration.
PMID- 28424976
TI - The Involvement of NR2B and tau Protein in MG132-Induced CREB Dephosphorylation.
AB - Transcription factor cAMP response element-binding protein (CREB) plays a
critical role in memory formation. Ubiquitin-proteasome system-dependent protein
degradation affects the upstream signaling pathways which regulate CREB activity.
However, the molecular mechanisms of proteasome inhibition on reductive CREB
activity are still unclear. The current study demonstrated that MG132-inhibited
proteasome activity resulted in a dose dependence of CREB dephosphorylation at
Ser133 as well as decreased phosphorylation of N-methyl-D-aspartate (NMDA)
receptor subunit NR2B (Tyr1472) and its tyrosine protein kinase Fyn (Tyr416).
These dephosphorylations are probably caused by disturbance of expression and
post-translational modifications of tau protein since tau siRNA decreased the
activity of Fyn, NR2B, and CREB. To further confirm this perspective, HEK293
cells stably expressing human tau441 protein were treated with MG132 and
dephosphorylations of CREB and NR2B were observed. The current research provides
an alternative pathway, tau/Fyn/NR2B signaling, regulating CREB activity.
PMID- 28424977
TI - Restless legs syndrome and tension-type headache: a population-based study.
AB - BACKGROUND: Recent studies have shown a significant association between restless
legs syndrome (RLS) and primary headache disorders. Nevertheless, information
regarding the association between tension-type headache (TTH) and RLS is limited.
This study aimed to investigate the association between RLS and TTH in a
population-based sample. METHODS: We selected a stratified random population
sample of Koreans aged 19-69 years and assessed them using a semi-structured
interview designed to identify RLS, headache type, and clinical characteristics
of TTH. We determined the prevalence and clinical impact of RLS in participants
with TTH. RESULTS: Of the 2695 participants, 570 (21.2%) and 142 (5.3%) were
classified as having TTH and RLS, respectively. Among the 570 individuals with
TTH, 113 (19.8%) also met the criteria for probable migraine (PM). The prevalence
of RLS was significantly higher among individuals with TTH than among those with
non-headache (6.0% vs 3.6%, p = 0.018). The prevalence of RLS was significantly
higher in subjects with TTH who fulfilled PM criteria than in those with non
headache participants (8.0% vs. 3.6%, p = 0.018). However, RLS prevalence in
individuals with TTH who did not fulfil PM criteria did not differ from that of
participants with non-headache (5.5% vs. 3.6%, p = 0.063). TTH participants with
RLS had higher visual analogue scale scores for headache intensity (5.1 +/- 2.0
vs. 4.3 +/- 1.8, p = 0.038), and higher prevalence of anxiety (20.6% vs. 8.8%, p
= 0.022) and depression (14.7% vs. 3.5%, p = 0.002) than TTH participants without
RLS. Multivariable analyses revealed that headache aggravation by movement (odds
ratio [OR] = 2.4, 95% confidence interval [CI] = 1.1-5.2) and depression (OR =
3.5, 95% CI = 1.1-11.4) were significant indicators of RLS among individuals with
TTH. CONCLUSIONS: The prevalence of RLS was higher among individuals with TTH
than among those with non-headache. Some clinical presentations varied in
accordance with the presence of RLS among participants with TTH.
PMID- 28424978
TI - The Physicochemical Investigation of 17beta-Estradiol Crystalline Prepared by In
Situ pH-Dependent Solubility Technique with Polyvinylpyrrolidone.
AB - Micro-particles of 17beta-estradiol (ED) were prepared with polyvinylpyrrolidone
(PVP) by in situ pH-dependent solubility technique. Products were characterized
using multiple instruments, and molecular interactions between ED and PVP were
explored. Powder X-ray diffraction and thermal analysis revealed crystalline ED
in the micro-particles is hemihydrated. PVP was also present in the micro
particles. Laser particle size analysis and scanning electron microscopy revealed
thin slice morphology, which might have resulted from the influence of PVP.
Moreover, the results of contact angle, specific surface area, and dynamic vapor
sorption showed that the surface properties of products were improved. These
physicochemical properties of the micro-particles resulted in an obvious
improvement in dissolution rate. Fourier transform infrared spectroscopy and 1H
nuclear magnetic resonance revealed hydrogen bonding between ED and PVP. A method
was established for the preparation of micro-particles through the addition of
PVP during the reaction process.
PMID- 28424979
TI - Studies on Core-Shell Nanocapsules of Felodipine: In Vitro-In Vivo Evaluations.
AB - The present study aimed for in vitro-in vivo-in silico simulation studies of
experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F
127 nanocapsules to ferry felodipine using GastroPlusTM. The in silico parameter
sensitivity analysis for pharmacokinetic parameters was initially assessed to
justify the preparation of felodipine-loaded nanocapsules (FLNs) with enhanced
solubility to overcome the bioavailability issues of felodipine. The overall
integrated desirability ranged between 0.8187 and 0.9488 for three optimized FLNs
when analyzed for mean particle size, zeta potential, encapsulation efficiency,
and in vitro dissolution parameters. The morphological evaluation (SEM, TEM, and
AFM) demonstrated spherical nanoparticles (200-300 nm). Validated LC-MS/MS
analysis demonstrated enhanced relative bioavailability (13.37-fold) of optimized
FLN as compared to suspension. The simulated regional absorption of the FLN
presented significant absorption from the cecum (26.3%) and ascending colon
(20.1%) with overall absorption of 67.4% from the GIT tract. Furthermore, in
vitro-in vivo correlation demonstrated the Wagner-Nelson method as the preferred
model as compared to mechanistic and numerical deconvolution on the basis of
least mean absolute prediction error, least standard error of prediction, least
mean absolute error, and maximum correlation coefficient (r 2 = 0.920). The study
demonstrated enhanced oral absorption of felodipine-loaded nanocapsules, and
GastroPlusTM was found to be an efficient simulation tool for in vitro-in vivo-in
silico simulations.
PMID- 28424980
TI - Capsule Commentary on Patel el al., Using Active Choice Within the Electronic
Health Record to Increase Influenza Vaccination Rates.
PMID- 28424981
TI - Capsule Commentary on Pololi et al., Assessing the Culture of Residency Using the
C-Change Resident Survey: Validity Evidence in 34 US Residency Programs.
PMID- 28424982
TI - Finding Common Ground: Educating General Psychiatry Residents About Forensic
Psychiatry.
PMID- 28424983
TI - The Effect of Gastrostomy Placement on Gastric Function in Children: a
Prospective Cohort Study.
AB - BACKGROUND: A gastrostomy placement is frequently performed in pediatric patients
who require long-term enteral tube feeding. Unfortunately, postoperative
complications such as leakage, feeding intolerance, and gastroesophageal reflux
frequently occur. These complications may be due to postoperative gastric
dysmotility. Our aim was to evaluate the effect of gastrostomy placement on
gastric emptying in children. METHODS: A prospective study was performed
including 50 children undergoing laparoscopic gastrostomy. Before and 3 months
after gastrostomy, assessment was performed using the 13C-octanoic acid breath
test, 24-h pH monitoring, and reflux symptom questionnaires. RESULTS: Gastric
half-emptying time significantly increased from the 57th to the 79th percentile
(p < 0.001) after gastrostomy (p < 0.001). Fifty percent of patients with normal
preoperative gastric emptying develop delayed gastric emptying (DGE, P > 95)
after gastrostomy (p = 0.01). Most patients (>=75%) with leakage and/or feeding
intolerance after gastrostomy had DGE after operation. A decrease in gastric
emptying was associated with an increase in esophageal acid exposure time (r =
0.375, p < 0.001). CONCLUSION: Gastrostomy placement in children causes a
significant delay in gastric emptying. Postoperative DGE was associated with
gastroesophageal reflux and was found in most patients with postoperative leakage
and feeding intolerance. These negative physiologic effects should be taken into
account when considering gastrostomy placement in children.
PMID- 28424984
TI - Management of Ingested Hijab-Pin.
AB - BACKGROUND AND STUDY AIMS: Accidental swallowing of hijab (or turban) pin was
reported mainly among adolescent girls. Current guidelines indicate emergent
intervention endoscopy in case a long sharp object is found in the
gastrointestinal tract. The aims of the current study are to present the results
of an observational approach and to assess the need for intervention. PATIENTS
AND METHODS: A retrospective cohort study was conducted including all 5-18-year
old patients who presented with hijab-pin ingestion between 2003 and 2014. The
need for intervention was assessed using both univariable and multivariable
statistical analyses. RESULTS: Two hundred three cases of hijab-pin ingestion
were documented. In the majority of cases, the pin was observed in the stomach
(137/203, 67.4%) upon arrival. Most pins that were located at the upper
gastrointestinal tract (proximal to the ligament of Treitz) ejected spontaneously
(120/169, 71%, Pv = 0.005). The absence of pin progression in an X-ray performed
12 h following presentation was significantly more frequent in the intervention
group (46/51, 90%, Pv = 0.001). CONCLUSIONS: In most cases, the outcome is
spontaneous ejection from the digestive tract. However, if needle location
remains unchanged on two consecutive X-rays, an endoscopic intervention is
recommended.
PMID- 28424985
TI - Postoperative Complications and Functional Outcome after Esophageal Atresia
Repair: Results from Longitudinal Single-Center Follow-Up.
AB - BACKGROUND: Esophageal atresia (EA) and tracheoesophageal fistula (TEF) represent
major therapeutic challenges, frequently associated with serious morbidities
following surgical repair. The aim of this longitudinal study was to assess
temporal changes in morbidity and mortality of patients with EA/TEF treated in a
tertiary-level center, focusing on postoperative complications and their impact
on long-term gastroesophageal function. METHODS: One hundred nine consecutive
patients with EA/TEF born between 1975 and 2011 were followed for a median of 9.6
years (range, 3-27 years). Comparative statistics were used to evaluate temporal
changes between an early (1975-1989) and late (1990-2011) study period. RESULTS:
Gross types of EA were A (n = 6), B (n = 5), C (n = 89), D (n = 7), and E (n =
2). Seventy (64.2%) patients had coexisting anomalies, 13 (11.9%) of whom died
before EA correction was completed. In the remaining 96 infants, surgical repair
was primary (n = 66) or delayed (n = 25) anastomosis, closure of TEF in EA type E
(n = 2), and esophageal replacement with colon interposition (n=2) or gastric
transposition (n=1). Long-gap EA was diagnosed in 23 (24.0%) cases. Postoperative
mortality was 4/96 (4.2%). Overall survival increased significantly between the
two study periods (42/55 vs. 50/54; P = 0.03). Sixty-nine (71.9%) patients
presented postoperatively with anastomotic strictures requiring a median of 3
(range, 1-15) dilatations. Revisional surgery was required for anastomotic
leakage (n = 5), recurrent TEF with (n = 1) or without (n=9) anastomotic
stricture, undetected proximal TEF (n = 4), and refractory anastomotic strictures
with (n = 1) or without (n = 2) fistula. Normal dietary intake was achieved in 89
(96.7%) patients, while 3 (3.3%) remained dependent on gastrostomy feedings.
Manometry showed esophageal dysmotility in 78 (84.8%) infants at 1 year of age,
increasing to 100% at 10-year follow-up. Fifty-six (60.9%) patients suffered from
dysphagia with need for endoscopic foreign body removal in 12 (13.0%) cases. Anti
reflux medication was required in 43 (46.7%) children and 30 (32.6%) underwent
fundoplication. The rate of gastroesophageal reflux increased significantly
between the two study periods (29/42 vs. 44/50; P = 0.04). Twenty-two (23.9%)
cases of endoscopic esophagitis and one Barrett's esophagus were identified.
CONCLUSIONS: Postoperative complications after EA/TEF repair are common and
should be expertly managed to reduce the risk of long-term morbidity. Regular
multidisciplinary surveillance with transitional care into adulthood is
recommended in all patients with EA/TEF.
PMID- 28424986
TI - Extremely Giant Liver Hemangioma (50 cm) with Kasabach-Merritt Syndrome.
AB - A 33-year-old male has been found with a giant liver hemangioma of initial size
29 cm for 5 years. He received arterial embolization twice in order to shrink the
tumor; however, no effect was obtained. The tumor had rapidly grown to 50 cm and
caused abnormalities in the hematological and coagulative systems. Preoperative
computed tomography revealed that the right hepatic vein, right hepatic artery,
and right portal vein were not involved by the hemangioma. Resection of the giant
liver hemangioma was successfully performed after intraoperative intentional
bloodletting with concurrent blood salvage. All hematological and coagulative
abnormalities had returned to normal after the procedure.
PMID- 28424987
TI - Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for
Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System.
AB - INTRODUCTION: The role of routine lymphadenectomy for intrahepatic
cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition
recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal
staging. We sought to define outcome and risk of death among patients who were
staged with >=6 HLNs versus <6 HLNs. MATERIALS AND METHODS: Patients undergoing
hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary
centers were identified. RESULTS: Among 1154 patients undergoing hepatectomy for
ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients
had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN).
Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did
not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was
associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged
according the AJCC eighth edition staging system, N1 patients had a 3-fold
increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001).
CONCLUSION: Only one fourth of patients undergoing hepatectomy for ICC had
adequate nodal staging according to the AJCC eighth edition. While the six HLN
cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN
was associated with long-term survival of N1 patients.
PMID- 28424989
TI - T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in
mice.
AB - BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators
of pain. In inflammatory conditions, the local release of opioids by leukocytes
at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia.
Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins
released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral
pain. The present study aims to investigate whether mucosal T-cell-derived
enkephalins also exhibit a potent anti-inflammatory activity as described for
exogenous opioid drugs in Th1/Th17-associated colitis. METHODS: The anti
inflammatory effects of endogenous opioids were investigated in both Th1/Th17
associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated
(oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+
T cell subsets were compared in mice treated or not treated with naloxone
methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory
activity of T-cell-derived enkephalins was further estimated by comparison of
colitis severity in immunodeficient mice into which naive CD4+CD45RBhigh T
lymphocytes originating from wild-type or enkephalin-knockout mice had been
transferred. RESULTS: Peripheral opioid receptor blockade increases the severity
of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite
effects of naloxone methiodide treatment in these two models of intestinal
inflammation are dependent on the potency of endogenous opioids to promote a Th2
type immune response. Accordingly, the transfer of enkephalin-deficient
CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation
induced colonic injury. CONCLUSIONS: Endogenous opioids, including T-cell-derived
enkephalins, promote a Th2-type immune response, which, depending on the context,
may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated)
intestinal inflammation.
PMID- 28424988
TI - Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis
proteins (IAPs).
AB - Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant
role in the control of programmed cell death (PCD). PCD is essential to maintain
healthy cell turnover within tissue but also to fight disease or infection.
Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression.
Therefore, it is unsurprising that cancer cells demonstrate significantly
elevated expression levels of IAPs, resulting in improved cell survival, enhanced
tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has
garnered substantial scientific interest and as resistance to anti-cancer agents
becomes more prevalent, targeting IAPs has become an increasingly attractive
strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies
and TRAIL therapy. Antagonism strategies to modulate the actions of XIAP, cIAP1/2
and survivin are the central focus of current research and this review highlights
advances within this field with particular emphasis upon the development and
specificity of second mitochondria-derived activator of caspase (SMAC) mimetics
(synthetic analogs of endogenously expressed inhibitors of IAPs SMAC/DIABLO).
While we highlight the potential of SMAC mimetics as effective single agent or
combinatory therapies to treat cancer we also discuss the likely clinical
implications of resistance to SMAC mimetic therapy, occasionally observed in
cancer cell lines.
PMID- 28424990
TI - Proteomic Analysis of the Hippocampus in Mouse Models of Trigeminal Neuralgia and
Inescapable Shock-Induced Depression.
AB - To investigate the behavioral and biomolecular similarity between neuralgia and
depression, a trigeminal neuralgia (TN) mouse model was established by
constriction of the infraorbital nerve (CION) to mimic clinical trigeminal
neuropathic pain. A mouse learned helplessness (LH) model was developed to
investigate inescapable foot-shock-induced psychiatric disorders like depression
in humans. Mass spectrometry was used to assess changes in the biomolecules and
signaling pathways in the hippocampus from TN or LH mice. TN mice developed not
only significant mechanical allodynia but also depressive-like behaviors (mainly
behavioral despair) at 2 weeks after CION, similar to LH mice. MS analysis
demonstrated common and distinctive protein changes in the hippocampus between
groups. Many protein function families (such as cell-to-cell signaling and
interaction, and cell assembly and organization,) and signaling pathways (e.g.,
the Huntington's disease pathway) were involved in chronic neuralgia and
depression. Together, these results demonstrated that the LH and TN models both
develop depressive-like behaviors, and revealed the involvement of many
psychiatric disorder-related biomolecules/pathways in the pathogenesis of TN and
LH.
PMID- 28424991
TI - Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root
Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and
Regulation by Paclitaxel.
AB - Voltage-gated sodium channels (Navs) play an important role in human pain
sensation. However, the expression and role of Nav subtypes in native human
sensory neurons are unclear. To address this issue, we obtained human dorsal root
ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed
Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of
total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse
DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1.7 (~18%).
To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary
cultures with paclitaxel (0.1-1 MUmol/L) for 24 h. Paclitaxel increased the
Nav1.7 but not Nav1.8 expression and also increased the transient Na+ currents
and action potential firing frequency in small-diameter (<50 MUm) hDRG neurons.
Thus, the hDRG provides a translational model in which to study "human pain in a
dish" and test new pain therapeutics.
PMID- 28424993
TI - Performing corneal crosslinking under local anaesthesia in patients with Down
syndrome.
AB - PURPOSE: To report on the ability to perform corneal crosslinking (CXL) under
local anaesthesia for the treatment of keratoconus in patients with Down
syndrome. METHODS: Nine eyes of seven patients with both keratoconus and Down
syndrome were scheduled for an epithelium-off CXL procedure under local
anaesthesia. Exclusion criteria were a corneal thickness under 400 um and the
presence of corneal scars. A standardized clinical decision tool was used to
estimate patient cooperation and the likelihood for a successful procedure under
local rather than general anaesthesia. RESULTS: In seven eyes, the CXL was
completed successfully. The treatment was aborted in two eyes due to insufficient
corneal thickness (<400 um) prior to ultraviolet-A irradiation, even after
employing hypoosmolar riboflavin. No adverse events occurred post-operatively,
except for one case of delayed epithelial healing (23 days). CONCLUSIONS: With a
proper patient selection, CXL under local anaesthesia can be achieved in patients
with Down syndrome.
PMID- 28424992
TI - Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to
punctate inner choroidopathy.
AB - PURPOSE: To assess the outcome of patients with choroidal neovascularization
(CNV) secondary to punctate inner choroidopathy (PIC) receiving intravitreal anti
VEGF (vascular endothelial growth factor) injections. METHODS: Sixteen eyes of 16
patients diagnosed with CNV secondary to PIC were retrospectively assessed.
RESULTS: Eleven women and five men with a mean age of 35 years (SD 11, range 16
56 years) received intravitreal anti-VEGF for PIC-related CNV. On average, 3.5
injections (SD 2.7, range 1-9) were given per eye. Thirteen eyes were treated
with bevacizumab, two eyes with ranibizumab and one eye received both substances.
The mean follow-up was 15 months (SD 11, range 6-40 months). BCVA improved in
eight eyes (mean Delta +2.8 lines), remained stable in four eyes and decreased in
four eyes (mean Delta -4.3 lines). CONCLUSIONS: CNV development is a frequent
complication of PIC. Intravitreal anti-VEGF therapy seems to be safe and
effective for PIC-related CNV.
PMID- 28424994
TI - Modulation of gastrointestinal motility beyond metoclopramide and domperidone :
Pharmacological and clinical evidence for phytotherapy in functional
gastrointestinal disorders.
AB - The prokinetic cisapride, an important therapeutic option in functional
gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due
to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP)
and domperidone in functional GI disorders (FGID) was restricted, consequently
leaving a therapeutic gap in clinical practice. A systematic review revealed that
the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent
to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in
randomized controlled clinical trials (RCTs) in functional dyspepsia and
irritable bowel syndrome, based on its multitarget effect on numerous etiological
factors. Due to an outstanding favorable safety profile, STW 5 allows an
effective and safe use in FGID without a limitation of the duration of the
treatment.
PMID- 28424995
TI - The emergence of vancomycin-resistant Staphylococcus aureus in an intensive care
unit in Kerman, Iran.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a global threat to public
health. This study is the first report of the emergence of vancomycin-resistant
MRSA in Kerman, Iran. During a period of 15 months, a total of 205 clinical
isolates of S. aureus were collected from three university hospitals affiliated
with the Kerman University of Medical Science, Kerman, Iran. Screening of
methicillin and vancomycin resistance was carried out by phenotypic methods. The
resistance and virulence genes of vancomycin-resistant isolates were detected by
polymerase chain reaction (PCR). Staphylococcal cassette chromosome mec (SCCmec)
and spa typing were used for molecular typing of vancomycin-resistant isolates.
Two S. aureus isolates were considered vancomycin-resistant by phenotypic and
genotypic methods. Both isolates showed a minimum inhibitory concentration (MIC)
>= 64 ug/ml and belonged to SCCmec III and spa type t030. Finding vancomycin
resistant S. aureus (VRSA) isolates represents a serious problem. More stringent
infection control policies are recommended to prevent transmission of such life
threatening isolates in the hospital setting.
PMID- 28424996
TI - [Quality assurance of pain care in Austria : Classification of management
facilities].
AB - In Austria there is no nationwide coverage of pain management, which meets even
approximately international criteria. At present there are about 30
interdisciplinary pain management offices and clinics providing care according to
a concept of the Austrian Pain Society (OSG), about 10 other outpatient pain
clinics are located in district and country hospitals. A few years ago, there
still were about 50 pain clinics. Yet closure of outpatient clinics and cost
cutting measures in the health sector jeopardize adequate pain relief for
patients with chronic pain conditions.Hence, the supply of care for approx. 1.8
mio. Austrians with chronic pain is not guaranteed due to lack of a comprehensive
demand planning of pain care facilities. Furthermore, existing structures such as
specialized clinics or emergency services in hospitals are primarily based on the
personal commitment of individuals. At present, the various centres for pain
management in Austria are run with very different operating times, so that for
74% of the chronic pain patients the desired requirements for outpatient pain
management are not met and about 50 full-time pain clinics are missing.Under the
patronage of the Austrian Pain Society, various national specialist societies
have defined the structure and quality criteria for pain management centres in
Austria, include, among others, proof of training, cooperation in
interdisciplinary teams or minimum number of new patients per year, depending on
the classification of the institution.This stepwise concept of care provision for
pain patients is intended as first step to help improve the care of pain patients
in Austria!
PMID- 28424997
TI - Changing Places, Changing Plates? A Binational Comparison of Barriers and
Facilitators to Healthful Eating Among Central American Communities.
AB - To understand the process by which immigrants adopt dietary practices, this study
offers a binational comparison of factors that predispose, enable, and reinforce
healthful eating in the sending and receiving countries. Data are from two
qualitative studies that examined barriers and facilitators to healthful eating
in El Salvador (four focus groups, n = 28 adults) and in the US (30 in-depth
interviews n = 15 mothers recently migrated from Central America). There was a
strong emphasis on hygiene and vitamin-content of foods among participants in El
Salvador. In both settings, participants perceived that their respective
community food environments (schools, food stores) exposed their families to
highly processed, unhealthful foods. In both settings, they described similar
struggles to encourage their families to eat foods healthfully (traditional, home
made foods). These results underscore the importance of acknowledging the
changing food environment in sending countries where people may already be
exposed to processed foods.
PMID- 28424998
TI - Correlates and Predictors of Mobility Limitation in Community-Dwelling Hispanic
Older Adults in the United States: A Systematic Review.
AB - This article presents a systematic review of the literature on
correlates/predictors of mobility limitation among community-dwelling U.S.
Hispanic older adults. A search of scientific databases (PubMed, CINAHL, and
PsycINFO) was conducted. After abstract and full text review, 20 epidemiologic
studies that met all eligibility criteria were included. The theoretical
framework of mobility was used to categorize factors related to mobility
limitation. The majority of the studies reviewed (n = 17) examined some aspect of
physical factors in relation to mobility limitation. Several factors emerged as
important influences on mobility outcomes: diabetes mellitus, stroke, obesity,
arthritis, and depression. None examined the influence of built environment. This
review suggests that multilevel factors can impact both mobility limitations and
disability among U.S. Hispanic older adults. However, the study findings were
inconsistent, with some studies showing significant relationships or effects and
others demonstrating no associations or mixed findings.
PMID- 28424999
TI - Alcohol use Exacerbates Acculturative Stress Among Recently Immigrated, Young
Adult Latinas.
AB - Associations between theorized sociocultural factors and acculturative stress
were examined among Latina immigrants (aged 18-23 years) during their initial
months in the US. Participants' quantity of alcohol use was hypothesized to be
linked with more acculturative stress. Using respondent-driven sampling, 530
Latinas who recently immigrated to Miami-Dade County, Florida, were recruited
from community activities, Latino health fairs, advertisements at community
agencies, and online postings. A path analysis revealed associations between
acculturative stress and more time in the US and greater commitment to ethnic
identity. Marianismo gender role beliefs differentially related with
acculturative stress. Quantity of alcohol use moderated the positive association
between time in US and acculturative stress, such that women in the US for less
time who drank more alcohol experienced higher levels of acculturative stress
than their peers. Findings suggest quantity of alcohol use may exacerbate
acculturative stress during some Latina young adult immigrants' initial months in
the US.
PMID- 28425000
TI - Medical Care, Screening and Regularization of Sub-Saharan Irregular Migrants
Affected by Hepatitis B in France and Italy.
AB - Both in France and in Italy hepatitis B is present mostly among the migrant
population coming from sub-Saharan Africa and mainly among those migrants having
a poor socio-economic background. This article is aimed at assaying the impact of
public policies adopted by France and Italy for migrants' health on the treatment
of migrants with HBV. The article is based on semi-structured interviews
conducted with 30 immigrant adults taken into care by two associations dealing
with medical, psychological and social issues of immigrants applying for a
residence permit, mainly asylum seekers. The results of this study bring to light
specific difficulties relating to national contexts, to the type of HBV (inactive
or active) and to the administrative situation of the migrants. In France
irregular migrants are screened in humanitarian associations. In Italy the
screening is done in public hospitals. In both countries, only migrants suffering
from chronic hepatitis B obtain a residence permit for medical reasons. More
migrants in Italy than in France abandon HBV treatment. This study describes how
specific national immigration and health policies impact in a different way the
therapeutic and social path of migrants suffering from hepatitis B. The analysis
provides useful material for the development of strategies to prevent and control
hepatitis B among the migrant population. It also shows how social determinants
affect migrants' health more than values or cultural factors do.
PMID- 28425002
TI - Beyond study participants: a framework for engaging patients in the selection or
development of clinical outcome assessments for evaluating the benefits of
treatment in medical product development.
AB - BACKGROUND: Patients are participating more actively in health care decision
making with regard to their health, as well as in the broader realm of assessing
the value of medical products and influencing decisions about their registration
and reimbursement. There is an increasing trend to include patients' perspectives
throughout the stages of medical product development by broadening the
traditional study-participant role to that of an active partner throughout the
process. Including patients in the selection and development of clinical outcome
assessments (COAs) to evaluate the benefit of treatment is particularly
important. Still, despite widespread enthusiasm, there is substantial uncertainty
regarding how and when to engage patients in this process. PURPOSE: This
manuscript proposes a methodological framework for engaging patients at varying
levels in the selection and development of COAs for medical product development.
FRAMEWORK: The framework builds on the Food and Drug Administration's roadmap for
patient-focused COA. Methods for engaging patients across each stage in this
roadmap are summarized by levels of engagement. Opportunities and examples of
patient engagement (PE) in the selection and/or development of COAs are
summarized, together with best practices and practical considerations.
CONCLUSION: This paper offers a framework for understanding, planning, and
implementing methods to advance PE in the selection and/or development of COAs
for evaluating the benefit of medical products. The intent is to further this
important discussion and enhance the process and outcome of PE in this context.
PMID- 28425003
TI - Validation of the Persian version of the Daily Spiritual Experiences Scale (DSES)
in Pregnant Women: A Proper Tool to Assess Spirituality Related to Mental Health.
AB - Assessing spirituality in healthy pregnant women may lead to supportive
interventions that will improve their care. A psychometrically valid measure such
as the Daily Spiritual Experiences Scale (DSES) may be helpful in this regard.
The current study sought to adapt a Persian version of DSES for use in pregnancy.
A total of 377 pregnant women were recruited from three general hospitals located
in Tehran, Iran. Administered scales were the DSES, Duke University Religion
Index, Santa Clara Strength of Religious Faith scale, and Depression Anxiety
Stress Scale, as well as demographic measures. Reliability of the DSES was tested
using Cronbach's alpha for internal consistency and the intraclass correlation
coefficient (ICC) for test-retest stability. Scale validity was assessed by
criterion-related tests, known-groups comparison, and exploratory factor
analysis. Participant's mean age was 27.7 (4.1), and most were nulliparous (70%).
The correlation coefficient between individual items on the scale and the total
score was greater than 0.30 in most cases. Cronbach's alpha for the scale was
0.90. The ICC for 2-week test-retest reliability was high (0.86). Relationships
between similar and dissimilar scales indicated acceptable convergent and
divergent validity. The factor structure of the scale indicated a single factor
that explained 59% of the variance. The DSES was found to be a reliable and valid
measure of spirituality in pregnant Iranian women. This scale may be used to
examine the relationship between spirituality and health outcomes, research that
may lead to supportive interventions in this population.
PMID- 28425004
TI - On the Inner Life of Physicians: Analysis of Family Medicine Residents' Written
Reflections.
AB - This qualitative study introduces the broad and inclusive concept of the "inner
life of physicians" and analyzes the written reflections (N = 756) of family
medicine residents (N = 33) during their residency as indicative of the
physicians' inner lives. Residents completed reflective entries without specific
prompts. Researchers describe unsolicited emergent categorical themes indicative
of a robust inner life of the physician. Nurturing physicians' inner life through
reflection allows physicians to recognize, identify, and respond to daily
emotional events. Reflections about the state of physicians' inner lives can
formulate and express fundamental human questions that concern: (a) troubling
human experiences (e.g., suffering, death, luck, destiny, and death); (b)
questions that surface in practicing their profession; (c) spiritually explicit
questions on their beliefs and practices. Physicians' inner lives can become a
"place" where physicians look for answers and explore options for dealing with
their human and professional challenges, thus enhancing the humanistic aspects of
medical practice.
PMID- 28425005
TI - Is Spiritual Well-Being Among Adolescents Associated with a Lower Level of
Bullying Behaviour? The Mediating Effect of Perceived Bullying Behaviour of
Peers.
AB - The aim of this study was to explore the association between spiritual well-being
and bullying among Slovak adolescents, and whether perceived bullying behaviour
of peers mediated this relationship. Data from the Health Behaviour in School
aged Children study conducted in 2014 in Slovakia were used. Data were obtained
from 9250 adolescents with a mean age of 13.48 years. The final sample consisted
of 762 adolescents aged 15 years old (52.2% boys). We used logistic regression
models and the Sobel test. Adolescents who reported a higher level of spiritual
well-being were at lower risk of reporting that some or more schoolmates bully
others or that they themselves bully others. These relationships were partially
mediated by perceived norms about the bullying behaviour of schoolmates.
Spiritual well-being was found to be negatively associated with bullying; in
addition, a mediating role of perceived bullying behaviour of peers in this
relationship was confirmed.
PMID- 28425006
TI - Religiosity, Gender, and Natural Disasters: A Qualitative Study of Disaster
Stricken Regions in Iran.
AB - While religiosity is emerging as one of the more important subjects in disaster
management, identifying gender differences in using religion as a coping method
has attracted very little attention. The aim of this study was to explore the
effects of religiosity on disaster-affected women and men in the setting of Iran.
A field-based investigation using a qualitative approach was carried out to
achieve the study's purpose. Data were collected using in-depth unstructured
interviews with 25 participants who had been damaged by recent disasters. Two
themes, negative and positive effects of religiosity, and five categories were
extracted from the data. Women may be influenced by religion more than men, and
thus, they can play key roles in strengthening the positive effects of
religiosity.
PMID- 28425007
TI - "No More Buzz": A Qualitative Study of the Current Response to HIV in the
Anglican Church in the Western Cape, South Africa.
AB - Using a triangulation design combining participant observation, survey results,
and interviews, this paper studies the current form of the response to HIV in the
local Anglican Church in the Western Cape, South Africa. The results show that
people are generally aware of HIV. The "buzz" around HIV has, however, subsided.
The local church does not directly engage HIV anymore, and HIV is more mentioned
than talked about. HIV stigma continues to pose a challenge. To work towards the
prevention of HIV, the local church needs to put HIV back on the agenda and
continue to speak about the virus.
PMID- 28425008
TI - Reversible Activation of Halophilic beta-lactamase from Methanol-Induced Inactive
Form: Contrast to Irreversible Inactivation of Non-Halophilic Counterpart.
AB - Effects of a water-miscible organic solvent, methanol, on the structure and
activity of halophilic beta-lactamase derived from Chromohalobacter sp.560
(HaBla), were investigated by means of circular dichroism (CD) measurement and
enzymatic activity determination. Beta-lactamase activity was enhanced about 1.2
fold in the presence of 10-20% methanol. CD measurement of HaBla revealed
different structures depending on the methanol concentration: native-like active
form (Form I) in 10-20% methanol and methanol-induced inactive form at higher
concentration (Form II in 40-60% and Form III in 75-80% methanol). Incubation of
HaBla with 40% methanol led to the complete loss of activity within ~80 min
accompanied by the formation of Form II, whose activity was recovered promptly up
to ~80% of full activity upon dilution of the methanol concentration to 10%. In
addition, when the protein concentration was sufficiently high (e.g., 0.7 mg/ml),
HaBla activity of Form III in 75% methanol could be recovered in the same way
(with slightly slower recovery rate), upon dilution of the methanol
concentration. In contrast, non-halophilic beta-lactamase from Escherichia coli
K12 strain MG1655 (EcBla) was irreversibly denatured in the presence of 40%
methanol. HaBla showed remarkable ability to renature from the methanol-induced
inactive states.
PMID- 28425009
TI - The Molecular Genetic Expression as a Novel Biomarker in the Evaluation and
Monitoring of Patients With Osteosarcoma-Subtype Bone Cancer Disease.
AB - One of the leading causes of death among patients with malignancies is
represented by bone cancer. According to current studies, the leading cause of
death among these patients is represented by late diagnosis, poor response to
therapy, and the lack of accuracy in terms of clinical evaluation. In this
regard, there have been developed a series of methods of diagnosis and
evaluation, the most investigated being represented by miRNA expression. In this
updated work, we want to present a series of changes in the expression of miRNAs
in bone cancer. Moreover, we want to present the implications of miRNAs in
targeted therapy in such patients. Studies available in scientific databases such
as PubMed and Scopus were examined. The studies were searched using the keywords
"miRNAs expression", "bone cancer", "genetic therapy" and "genetic biomarkers."
For the evaluation and monitoring of bone cancer, the expression of miRNAs can be
successfully used due to increased specificity. Using miRNAs as gene therapy can
be also considered a therapeutic method of the future, mainly due to selective
and targeted response of the body.
PMID- 28425010
TI - A novel fibrinogen variant: dysfibrinogenemia associated with gammaAsp185Asn
substitution.
AB - To identify the pathogenesis of a Chinese woman diagnosed with dysfibrinogenemia.
A patient from Nanjing presented with a low plasma concentration of fibrinogen
and a normal level of antigen of fibrinogen. This abnormality was also detected
in her son. To detect whether the genetic mutation was responsible for the
dysfibrinogenemia, genomic DNA was extracted and amplified by polymerase chain
reaction, and DNA sequencing was performed on the purified PCR products.
Restriction fragment length polymorphism (RFLP), molecular modeling and
homologous sequences alignment were performed. Two heterozygous missense
variants, AalphaArg16His and gammaAsp185Asn, were discovered in the proband. Only
the former was detected in her son. AalphaArg16His had been reported by other
teams, and gammaAsp185Asn was identified first in our study as a novel variant.
RFLP was performed and indicated that the novel failed to be found in normal
subjects. Furthermore, it was suggested to be responsible for dysfibrinogenemia
depending on the molecular modeling and homologous sequence alignment. The
heterozygous AalphaArg16His and gammaAsp185Asn identified in the study probably
underlie the dysfibrinogenemia in this pedigree, with the latter being identified
for the first time.
PMID- 28425011
TI - Pregnancy-related myocardial infarction.
AB - INTRODUCTION: The risk of acute myocardial infarction in young women is low, but
increases during pregnancy due to the physiological changes in pregnancy,
including hypercoagulability. Ischaemic heart disease during pregnancy is not
only associated with increased maternal morbidity and mortality, but also with
high neonatal complications. Advancing maternal age and other risk factors for
cardiovascular diseases may further increase the risk of ischaemic heart disease
in young women. METHODS: We searched the coronary angiography database of a Dutch
teaching hospital to identify women with acute myocardial infarction who
presented during pregnancy or postpartum between 2011 and 2013. RESULTS: We found
two cases. Both women were in their early thirties and both suffered from
myocardial infarction in the postpartum period. Acute myocardial infarction was
due to coronary stenotic occlusion in one patient and due to coronary artery
dissection in the other patient. Coronary artery dissection is a relatively
frequent cause of myocardial infarction during pregnancy. Both women were treated
by percutaneous coronary intervention and survived. CONCLUSION: Physicians should
be aware of the increased risk of myocardial infarction when encountering
pregnant or postpartum women presenting with chest pain.
PMID- 28425013
TI - Cannabinoids as Modulators of Cell Death: Clinical Applications and Future
Directions.
AB - Endocannabinoids are bioactive lipids that modulate various physiological
processes through G-protein-coupled receptors (CB1 and CB2) and other putative
targets. By sharing the activation of the same receptors, some phytocannabinoids
and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids.
In recent years, a growing interest has been dedicated to the study of
cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and
neuroprotective effects. In addition to these well-recognized effects, various
studies suggest that cannabinoids may affect cell survival, cell proliferation or
cell death. These observations indicate that cannabinoids may play an important
role in the regulation of cellular homeostasis and, thus, may contribute to
tissue remodelling and cancer treatment. For a long time, the study of
cannabinoid receptor signalling has been focused on the classical adenylyl
cyclase/cyclic AMP/protein kinase A (PKA) pathway. However, this pathway does not
totally explain the wide array of biological responses to cannabinoids. In
addition, the diversity of receptors and signalling pathways that
endocannabinoids modulate offers an interesting opportunity for the development
of specific molecules to disturb selectively the endogenous system. Moreover,
emerging evidences suggest that cannabinoids ability to limit cell proliferation
and to induce tumour-selective cell death may offer a novel strategy in cancer
treatment. This review describes the main properties of cannabinoids in cell
death and attempts to clarify the different pathways triggered by these compounds
that may help to understand the complexity of respective molecular mechanisms and
explore the potential clinical benefit of cannabinoids use in cancer therapies.
PMID- 28425012
TI - A study of the damage of the intestinal mucosa barrier structure and function of
Ctenopharyngodon idella with Aeromonas hydrophila.
AB - The aim of this study is to explore the effect of Aeromonas hydrophila on the
intestinal mucosal barrier structure and intestinal permeability in grass carp
(Ctenopharyngodon idella). Histopathological examinations showed that A.
hydrophila induced severe intestinal lesions, including inflammatory cell
infiltration and intestinal villus fusion and swelling. Messenger RNA (mRNA)
expression of the inflammatory cytokines TNF-alpha, IL-1beta, IL-8, IL-10 and
MyD88 was significantly increased after infection with A. hydrophila. The
permeability of intestinal mucosa was determined using Evans blue (EB) and D
lactic acid. The results indicated that the levels of EB and serum D-lactic acid
were significantly increased after infection with A. hydrophila (p < 0.05). Our
results also indicated that the intestinal mucosal barrier injury induced by A.
hydrophila infection was closely associated with the expression of the tight
junction (TJ) protein zonula occludens-1 (ZO-1), occludin, claudin b and claudin
c as well as the activity of Na+, K+-ATPase and Ca2+, Mg2+-ATPase. Lower mRNA
levels of occludin and lower Na+, K+-ATPase and Ca2+, Mg2+-ATPase activity in the
intestines were observed after challenge. ZO-1 and claudin c were significantly
increased 24 h after infection with A. hydrophila. The most interesting finding
was that claudin b also significantly increased 24 h after challenge and then
decreased to lower levels at 72, 120 and 168 h post-infection compared to the PBS
treated control group. The results demonstrated that grass carp infection with A.
hydrophila induced intestinal inflammation and impaired the structure and
function of the intestinal mucosal barrier.
PMID- 28425014
TI - Clinicopathological and prognostic significance of Ki-67 immunohistochemical
expression of distant metastatic lesions in patients with metastatic breast
cancer.
AB - BACKGROUND: Surgical biopsy of metastatic lesions followed by pathological
confirmation for the investigation of biomarkers is occasionally proposed as an
effective strategy in the treatment of metastatic breast cancer. However, few
reports have examined Ki-67 immunohistochemical expression in distant metastatic
lesions of breast cancer patients. This study aimed to investigate the
clinicopathological significance of subtypes and Ki-67 immunohistochemical
expression in metastatic breast cancer lesions. METHODS: We retrospectively
studied surgical specimens of primary breast cancer tumors and their
corresponding metastatic lesions from patients (n = 68) who underwent surgery for
primary breast cancer tumors between December 1977 and March 2013. Tissue
microarrays were constructed using primary and metastatic lesions, and were
stained with antibodies against estrogen receptor, progesterone receptor, human
epidermal growth factor receptor 2, and Ki-67. We also examined the
clinicopathological characteristics and outcome measures of patients with
metastatic breast cancer using primary and paired metastatic lesions. RESULTS:
Compared with the primary lesions, there was no significant difference in
subtypes in the metastatic lesions according to metastatic sites. Metastatic
lesions of the brain, viscera, and bone exhibited slightly higher levels of Ki-67
immunohistochemical expression compared with primary lesions. A Cox proportional
hazards model using multivariate analysis demonstrated that high Ki-67
immunohistochemical expression in distant metastatic lesions was associated with
poorer overall survival outcomes after biopsy of recurrence lesion (hazard ratio
2.307; 95% confidence interval 1.207-4.407, P = 0.011). CONCLUSIONS: High Ki-67
immunohistochemical expression levels in distant metastatic lesions were
independently associated with poorer overall survival outcomes after biopsy of
recurrence lesion in breast cancer patients.
PMID- 28425015
TI - The New Classification of Seizures by the International League Against Epilepsy
2017.
AB - PURPOSE OF REVIEW: This review presents the newly developed International League
Against Epilepsy (ILAE) 2017 classification of seizure types. RECENT FINDINGS:
The fundamental distinction is between seizures that begin focally in one
hemisphere of the brain, generalized onset seizures that apparently originate in
both hemispheres, and seizures of unknown onset. Focal seizures optionally can be
subclassified according to whether awareness (a surrogate marker for
consciousness) is intact or impaired. The next level of classification for focal
seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms,
hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior
arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic.
Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic,
myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms)
and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The
classification allows new types of focal seizures and a few new generalized
seizures, and clarifies terms used to name seizures.
PMID- 28425016
TI - A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the
differentiation between non-significant and significant fibrosis in patients with
chronic hepatitis C.
AB - INTRODUCTION: A simple non-invasive score (Fibrofast, FIB-5) was developed using
five routine laboratory tests (ALT, AST, alkaline phosphatase, albumin and
platelets count) for the detection of significant hepatic fibrosis in patients
with chronic hepatitis C. The FIB-4 index is a non-invasive test for the
assessment of liver fibrosis, and a score of <=1.45 enables the correct
identification of patients who have non-significant (F0-1) from significant
fibrosis (F2-4), and could avoid liver biopsy. The aim of this study was to
compare the performance characteristics of FIB-5 and FIB-4 to differentiate
between non-significant and significant fibrosis. METHOD: A cross-sectional study
included 604 chronic HCV patients. All liver biopsies were scored using the
METAVIR system. Both FIB-5 and FIB-4 scores were measured and the performance
characteristics were calculated using the ROC curve. RESULTS: The performance
characteristics of FIB-5 at >=7.5 and FIB-4 at <=1.45 for the differentiation
between non-significant fibrosis and significant fibrosis were: specificity
94.4%, PPV 85.7%, and specificity 54.9%, PPV 55.7% respectively. CONCLUSION: FIB
5 score at the new cutoff is superior to FIB-4 index for the differentiation
between non-significant and significant fibrosis.
PMID- 28425017
TI - Spineless cactus associated with Tifton hay or sugarcane bagasse may replace corn
silage in sheep diets.
AB - The effect of the replacement of corn silage with spineless cactus associated
with Tifton 85 hay or sugarcane bagasse was evaluated on the performance, body
weight components and sheep meat quality. Twenty-one Santa Ines male sheep with
initial body weight of 22.9 +/- 2.9 kg were used. They were confined in
individual stalls for 74 days receiving the following diets: corn silage +
concentrate (CS); spineless cactus + Tifton 85 hay + concentrate (TH); spineless
cactus + sugarcane bagasse + concentrate (SB). After the feedlot period, the
animals were slaughtered and their body components were weighed and sampled. Data
were submitted to Tukey's test at 5% probability. The average daily gain (0.25 vs
0.14 kg), cold carcass weight (13.3 vs 13.7 kg), loin muscularity (0.6 vs 0.4 kg)
and liver weight (0.7 vs. 0.5 kg) were higher (P < 0.05) for the TH diet when
compared to that for the CS. The physical-chemical parameters of meat were not
influenced (P > 0.05) by the treatments and presented about 20.1% of crude
protein, 6.1% of crude fat and shear force of 2.0 kgf/cm2. In complete diets for
sheep, Tifton 85 hay associated with spineless cactus provides greater weight
gain, cold carcass muscularity and organ weight when compared to those for
animals fed with corn silage as exclusive roughage. Sugarcane bagasse associated
with spineless cactus may replace corn silage in complete diets for sheep.
PMID- 28425018
TI - Hepatocellular Carcinoma and Liver Transplantation: Changing Patterns and
Practices.
AB - OPINION STATEMENT: Benefits of liver transplantation (LT) for patients with
hepatocellular carcinoma (HCC) are well established. However, there is debate
regarding optimal and equitable selection of patients best served by LT,
particularly in the face of limited organ availability. Herein, we discuss topics
regarding LT selection criteria for patients with HCC. Recent change in UNOS
policy currently mandates a 6-month observation period prior to priority listing
and institutes a cap of 34 MELD exception points for patients with HCC.
Additionally, two further proposed changes to UNOS policy include (1) requiring
locoregional therapy for those with small (2-3 cm) unifocal HCC prior to applying
for exception points and (2) allowing downstaging in select patients with UNOS T3
lesions. These policies move beyond simply using tumor burden to using markers of
tumor biology for selecting patients who have the lowest risk of post-transplant
recurrence and best chance at long-term post-transplant survival. Given
increasing time on transplant waiting lists and shortage of donor grafts, LT
should be reserved for patients who may achieve significant benefit compared to
non-transplant therapies. Potential benefit to HCC patients must be weighed
against the harm from delaying or precluding LT for non-HCC patients on the
waiting list, particularly in regions with limited donor availability. The
relative benefit of LT in patients with small (<3 cm) HCC is likely limited;
surgical resection (in absence of portal hypertension) and local ablative therapy
(if portal hypertension present) are both efficacious and more cost-effective and
should likely be regarded as first line therapies for these patients. Salvage LT
can be considered as a rescue option for those with recurrent disease.
Downstaging for selected patients with UNOS T3 lesions may identify those with
good tumor biology and acceptable post-transplant outcomes; however, current
studies have had a wide variation in reported outcomes. While awaiting more data,
a standardized downstaging protocol including a priori inclusion criteria and a
mandatory waiting time prior to LT to observe tumor biology likely yields the
best outcomes.
PMID- 28425019
TI - Posttraumatic Stress Disorder Symptoms and Problematic Overeating Behaviors in
Young Men and Women.
AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is a risk factor for obesity,
but the range of behaviors that contribute to this association are not known.
PURPOSE: The purpose of this study was to examine associations between self
reported PTSD symptoms in 2007, with and without comorbid depression symptoms,
and three problematic overeating behaviors in 2010, and to estimate the
associations of PTSD-related overeating behaviors with obesity. METHODS: Cross
sectional and longitudinal analyses included 7438 male (n = 2478) and female (n =
4960) participants from the Growing Up Today Study (mean age 22-29 years in
2010). Three eating behavior outcomes were assessed: binge eating (eating a large
amount of food in a short period of time with loss of control), top quartile of
coping-motivated eating (from the Motivations to Eat scale), and top quartile of
disinhibited eating (from the Three-Factor Eating Questionnaire). RESULTS: PTSD
symptoms were associated with two- to threefold increases in binge eating and top
quartile coping-motivated eating; having >=4 PTSD symptoms, relative to no PTSD
symptoms, was associated with covariate-adjusted RRs of 2.7 (95% CI 2.1, 3.4) for
binge eating, 2.1 (95% CI 1.9, 2.4) for the top quartile of coping-motivated
eating, and 1.5 (95% CI 1.3, 1.7) for the top quartile of disinhibited eating.
There was a trend toward PTSD symptoms in 2007 predicting new onset binge eating
in 2010. Having depression symptoms comorbid with PTSD symptoms further increased
risk of binge eating and coping-motivated eating. All eating behaviors were
associated with obesity. CONCLUSION: Clinicians treating patients with PTSD
should know of potential comorbid problematic eating behaviors that may
contribute to obesity.
PMID- 28425020
TI - Acoustic Properties of Cries in 12-Month Old Infants at High-Risk of Autism
Spectrum Disorder.
AB - There is preliminary evidence that infant siblings of children with Autism
Spectrum Disorder (ASD) have an atypical pattern of cry, characterized by higher
fundamental frequency and increased dysphonation. This prospective study
collected multiple cry samples of 12-month old siblings of children with ASD (n =
22, 'high-risk' group) and 12-month olds with no family history of ASD (n = 27,
'low risk' group). While there was no difference between groups in the
fundamental frequency or degree of phonation of the cry samples, the duration of
each cry unit was significantly shorter in the high-risk siblings (p < .05). The
six infant siblings who received a diagnosis of ASD at age two had amongst the
shortest recorded cry durations.
PMID- 28425021
TI - Is the Autism-Spectrum Quotient a Valid Measure of Traits Associated with the
Autism Spectrum? A Rasch Validation in Adults with and Without Autism Spectrum
Disorders.
AB - The Autism-Spectrum Quotient (AQ) is among the most widely used scales assessing
autistic traits in the general population. However, some aspects of the AQ are
questionable. To test its scale properties, the AQ was translated into Swedish,
and data were collected from 349 adults, 130 with autism spectrum disorder (ASD)
and 219 without ASD, and analysed with Rasch. Several scale properties of the AQ
were satisfactory but it did not meet the criterion of a unidimensional measure
of autistic traits. The Rasch analysis showed that the 50-item AQ could be
reduced to a 12-item subset with little loss of explanatory power, with the
potential to efficiently measure the degree to which adults with and without ASD
show autistic traits.
PMID- 28425022
TI - Social Motor Synchronization: Insights for Understanding Social Behavior in
Autism.
AB - Impairments in social interaction and communication are critical features of ASD
but the underlying processes are poorly understood. An under-explored area is the
social motor synchronization that happens when we coordinate our bodies with
others. Here, we explored the relationships between dynamical measures of social
motor synchronization and assessments of ASD traits. We found (a) spontaneous
social motor synchronization was associated with responding to joint attention,
cooperation, and theory of mind while intentional social motor synchronization
was associated with initiating joint attention and theory of mind; and (b) social
motor synchronization was associated with ASD severity but not fully explained by
motor problems. Findings suggest that objective measures of social motor
synchronization may provide insights into understanding ASD traits.
PMID- 28425023
TI - Challenges and Opportunities in Global Mental Health: a Research-to-Practice
Perspective.
AB - PURPOSE OF REVIEW: Globally, the majority of those who need mental health care
worldwide lack access to high-quality mental health services. Stigma, human
resource shortages, fragmented service delivery models, and lack of research
capacity for implementation and policy change contribute to the current mental
health treatment gap. In this review, we describe how health systems in low- and
middle-income countries (LMICs) are addressing the mental health gap and further
identify challenges and priority areas for future research. RECENT FINDINGS:
Common mental disorders are responsible for the largest proportion of the global
burden of disease; yet, there is sound evidence that these disorders, as well as
severe mental disorders, can be successfully treated using evidence-based
interventions delivered by trained lay health workers in low-resource community
or primary care settings. Stigma is a barrier to service uptake. Prevention,
though necessary to address the mental health gap, has not solidified as a
research or programmatic focus. Research-to-practice implementation studies are
required to inform policies and scale-up services. Four priority areas are
identified for focused attention to diminish the mental health treatment gap and
to improve access to high-quality mental health services globally: diminishing
pervasive stigma, building mental health system treatment and research capacity,
implementing prevention programs to decrease the incidence of mental disorders,
and establishing sustainable scale up of public health systems to improve access
to mental health treatment using evidence-based interventions.
PMID- 28425024
TI - Lesinurad: A Review in Hyperuricaemia of Gout.
AB - Lesinurad (Zurampic(r)) is an oral selective inhibitor of the URAT1 and OAT4 uric
acid (UA) transporters of the kidney, via which it inhibits UA reabsorption and
thus increases renal UA excretion and lowers serum UA (sUA) levels. Lesinurad 200
mg once daily is indicated for use in combination with a xanthine oxidase
inhibitor (XOI) to treat hyperuricaemia in adults with gout who have not achieved
target sUA levels with an XOI alone. Approval was based on three 12-month phase 3
trials that evaluated lesinurad in combination with allopurinol in adults with
gout inadequately responsive to allopurinol (CLEAR 1 and 2) and in combination
with febuxostat in adults with tophaceous gout (CRYSTAL). The target sUA level of
<6 mg/dL at 6 months (primary endpoint) was achieved by significantly more
lesinurad plus allopurinol than placebo plus allopurinol recipients in the CLEAR
trials. In CRYSTAL (which enrolled patients regardless of prior XOI experience,
and included 3 weeks of febuxostat before randomization), the proportion of
patients who achieved an sUA target of <5 mg/dL did not reach statistical
significance between lesinurad plus febuxostat and placebo plus febuxostat at 6
months (primary endpoint), although significantly favoured the lesinurad plus
febuxostat group at 12 months. Notably, the sUA target of <5 mg/dL at 6 months
was met with lesinurad plus febuxostat in the CRYSTAL subgroup that had
uncontrolled hyperuricaemia at baseline, despite having received febuxostat pre
randomization. Lesinurad plus XOI regimens were generally not associated with
improvements in flares and tophi in these trials, although clinical benefit
became more apparent in 12-month extension studies; the regimens were also
generally well tolerated. Thus, lesinurad, in combination with an XOI, is an
emerging option for the treatment of hyperuricaemia in adults with gout who have
not achieved target sUA levels with an XOI alone.
PMID- 28425025
TI - Light-induced formation of dimeric LHCII.
AB - It emerges from numerous experiments that LHCII, the major photosynthetic antenna
complex of plants, can appear not only in the trimeric or monomeric states but
also as a dimer. We address the problem whether the dimeric form of the complex
is just a simple intermediate element of the trimer-monomer transformation or if
it can also be a physiologically relevant molecular organization form? Dimers of
LHCII were analyzed with application of native electrophoresis, time-resolved
fluorescence spectroscopy, and fluorescence correlation spectroscopy. The results
reveal the appearance of two types of LHCII dimers: one formed by the
dissociation of one monomer from the trimeric structure and the other formed by
association of monomers into a distinctively different molecular organizational
form, characterized by a high rate of chlorophyll excitation quenching. The
hypothetical structure of such an energy quencher is proposed. The high light
induced LHCII dimerization is discussed as a potential element of the
photoprotective response in plants.
PMID- 28425026
TI - Photosynthetic responses to temperature across leaf-canopy-ecosystem scales: a 15
year study in a Californian oak-grass savanna.
AB - Ecosystem CO2 fluxes measured with eddy-covariance techniques provide a new
opportunity to retest functional responses of photosynthesis to abiotic factors
at the ecosystem level, but examining the effects of one factor (e.g.,
temperature) on photosynthesis remains a challenge as other factors may confound
under circumstances of natural experiments. In this study, we developed a data
mining framework to analyze a set of ecosystem CO2 fluxes measured from three
eddy-covariance towers, plus a suite of abiotic variables (e.g., temperature,
solar radiation, air, and soil moisture) measured simultaneously, in a
Californian oak-grass savanna from 2000 to 2015. Natural covariations of
temperature and other factors caused remarkable confounding effects in two
particular conditions: lower light intensity at lower temperatures and drier air
and soil at higher temperatures. But such confounding effects may cancel out. At
the ecosystem level, photosynthetic responses to temperature did follow a
quadratic function on average. The optimum value of photosynthesis occurred
within a narrow temperature range (i.e., optimum temperature, T opt): 20.6 +/-
0.6, 18.5 +/- 0.7, 19.2 +/- 0.5, and 19.0 +/- 0.6 degrees C for the oak canopy,
understory grassland, entire savanna, and open grassland, respectively. This
paradigm confirms that photosynthesis response to ambient temperature changes is
a functional relationship consistent across leaf-canopy-ecosystem scales.
Nevertheless, T opt can shift with variations in light intensity, air dryness, or
soil moisture. These findings will pave the way to a direct determination of
thermal optima and limits of ecosystem photosynthesis, which can in turn provide
a rich resource for baseline thresholds and dynamic response functions required
for predicting global carbon balance and geographic shifts of vegetative
communities in response to climate change.
PMID- 28425027
TI - 10-year results of On-X bileaflet mechanical heart valve in the aortic position:
low target INR regimen in Japanese.
AB - OBJECTIVES: This study was designed to establish clinical outcomes after aortic
valve replacement (AVR) with On-X bileaflet mechanical heart valve. METHODS:
Between 2006 and 2014, AVR was performed to 686 patients. Of them, 78 patients
using On-X valve were enrolled. The mean age was 65 +/- 11 years (ranged 33-85);
65% were men; and 81% were in sinus rhythm preoperatively. Calcific or
degenerative tricuspid aortic valve was present in 73%. Concomitant procedures
included coronary artery bypass grafting (22%), Bentall (8%), mitral valve
procedure (3%) and other (9%). They postoperatively received lower dose warfarin
[international normalized ratio (INR), 1.5-2.0] and 100 mg aspirin daily. The
follow-up duration averaged 5 years (386.6 patient-years). The follow-up rate was
97.3%. RESULTS: In-hospital mortality rates were 3.8% (n = 3). Late mortality
rates were 2.6% per patient-years (n = 10). Five-year Kaplan-Meier survival rates
were 84%. Freedom from major adverse valve-related stroke and cerebral bleeding
events was 93.3% (n = 5, 1.29% per patient-years) and 98.6% (n = 1, 0.26% per
patient-years, mild subdural hematoma). The incidence of stroke was two patients
of transient ischemic attack, two patients of paralytic event, one patient of
asymptomatic stroke (self-interruption of anticoagulation). The median INR was
1.92 +/- 0.53, ranged from 1.00 to 8.98 (n = 1181) and 51% of all measured INR
values were in the therapeutic range of 1.5-2.0. CONCLUSIONS: AVR using On-X
valve with low target INR regimen and low-dose aspirin resulted in a
significantly low risk of bleeding.
PMID- 28425028
TI - Energy harvesting from cerebrospinal fluid pressure fluctuations for self-powered
neural implants.
AB - In this paper, a novel method to generate electrical energy by converting
available mechanical energy from pressure fluctuations of the cerebrospinal fluid
within lateral ventricles of the brain is presented. The generated electrical
power can be supplied to the neural implants and either eliminate their battery
need or extend the battery lifespan. A diaphragm type harvester comprised of
piezoelectric material is utilized to convert the pressure fluctuations to
electrical energy. The pressure fluctuations cause the diaphragm to bend, and the
strained piezoelectric materials generate electricity. In the framework of this
study, an energy harvesting structure having a diameter of 2.5 mm was designed
and fabricated using microfabrication techniques. A 1:1 model of lateral
ventricles was 3D-printed from raw MRI images to characterize the harvester.
Experimental results show that a maximum power of 0.62 nW can be generated from
the harvester under similar physical conditions in lateral ventricles which
corresponds to energy density of 12.6 nW/cm2. Considering the available area
within the lateral ventricles and the size of harvesters that can be built using
microfabrication techniques it is possible to amplify to power up to 26 nW. As
such, the idea of generating electrical energy by making use of pressure
fluctuations within brain is demonstrated in this work via the 3D-printed model
system.
PMID- 28425029
TI - Comparison of a Novel Formulation of Abiraterone Acetate vs. the Originator
Formulation in Healthy Male Subjects: Two Randomized, Open-Label, Crossover
Studies.
AB - BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of
metastatic castration-resistant prostate cancer. The originator abiraterone
acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic
variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is
a proprietary formulation (using SoluMatrix Fine Particle TechnologyTM) designed
to increase the oral bioavailability of abiraterone acetate. Here, we report on
two phase I studies in healthy male subjects aged 18-50 years. METHODS: In Study
101, 20 subjects were randomized in a crossover design to single doses of AAFP
100, 200, or 400 mg or OAA 1000 mg taken orally under fasting conditions. Results
suggested that AAFP 500 mg would be bioequivalent to OAA 1000 mg in the fasted
state. To confirm the bioequivalence hypothesis and to further expand the AAFP
dose range, in Study 102, 36 subjects were randomized in a crossover design to
single doses of AAFP 125, 500, or 625 mg or OAA 1000 mg. Both studies included a
7-day washout period between administrations. RESULTS: Dose-dependent increases
in the area under the plasma concentration-time curve and maximum plasma
concentration with AAFP were observed in both studies. The AAFP 500-mg
bioavailability relative to OAA 1000 mg measured by the geometric mean ratio for
area under the plasma concentration-time curve from time zero to the time of the
last quantifiable concentration was 93.4% (90% confidence interval 85.3-102.4),
area under the plasma concentration-time curve from time zero to infinity was
91.0% (90% confidence interval 83.3-99.4), and maximum plasma concentration was
99.8% (90% confidence interval 86.3-115.5). Dose proportionality was seen across
all AAFP dose levels (100-625 mg). Abiraterone acetate fine particle was found to
be safe and well tolerated in this study. CONCLUSION: Abiraterone acetate fine
particle 500 mg was demonstrated to be bioequivalent to OAA 1000 mg in healthy
volunteers under fasted conditions.
PMID- 28425030
TI - Hand-eye calibration for surgical cameras: a Procrustean Perspective-n-Point
solution.
AB - PURPOSE: Surgical cameras are prevalent in modern operating theatres often used
as surrogates for direct vision. A surgical navigational system is a useful
adjunct, but requires an accurate "hand-eye" calibration to determine the
geometrical relationship between the surgical camera and tracking markers.
METHODS: Using a tracked ball-tip stylus, we formulated hand-eye calibration as a
Perspective-n-Point problem, which can be solved efficiently and accurately using
as few as 15 measurements. RESULTS: The proposed hand-eye calibration algorithm
was applied to three types of camera and validated against five other widely used
methods. Using projection error as the accuracy metric, our proposed algorithm
compared favourably with existing methods. CONCLUSION: We present a fully
automated hand-eye calibration technique, based on Procrustean point-to-line
registration, which provides superior results for calibrating surgical cameras
when compared to existing methods.
PMID- 28425031
TI - The cytokine expression in synovial membrane and the relationship with pain and
pathological findings at hip arthroscopy.
AB - BACKGROUND: Synovial membrane inflammation is the most common finding presenting
during hip arthroscopy, and may play a role in hip pain. We sought to determine
the relationships between synovial cytokine levels, hip pain, and arthroscopic
findings of the hip joint. METHODS: We prospectively included 33 patients who
underwent arthroscopic hip surgery (34 hips). For all patients, radiographs and
severity of pain were evaluated preoperatively. During arthroscopy, we classified
the chondral injury and synovitis, noted the incidence of labral tear and its
instability, and a sample of the synovial membrane was harvested for quantitative
PCR to determine levels of TNFalpha, IL1beta, IL6, ADAMTS4, MMP1, and MMP3. The
relationships between the levels of these cytokines, severity of hip pain, and
the pathological findings during arthroscopy were examined. RESULTS: Pain
intensity and cytokine levels were not significantly different between patients
with labral tear or instability and those without. By contrast, the expression of
TNFalpha, IL1beta, IL6, and MMP1 mRNA was significantly higher in patients with
diffuse synovitis than in patients with focal synovitis. VAS score during rest
showed significant positive correlation with IL6 (r = 0.45, p < 0.01), while VAS
score on walking showed a positive correlation with TNFalpha (r = 0.47, p <
0.01), and ADAMTS4 (r = 0.51, p < 0.01). The modified Harris Hip pain score
showed a negative correlation with TNFalpha (r = -0.38, p = 0.04) and IL6 (r =
0.58, p < 0.01). CONCLUSIONS: The severity of synovitis and chondral injury are
considered to be more important in the pathology of hip pain than labral tear or
instability. Inflammatory cytokines, especially TNFalpha and IL6 might play an
important role in the pathogenesis of pain in patients indicated for hip
arthroscopy, possibly depending on the severity of synovitis.
PMID- 28425032
TI - Parenting in On/Off Relationships: The Link Between Relationship Churning and
Father Involvement.
AB - Family systems theory points to the interconnected nature of dyadic relationships
within the family unit, arguing for attention to how the parental relationship
shapes their ties to and interactions with their children. Grounded in family
systems theory, we consider how relationship churning-defined as being in an on
again/off-again relationship with the same partner-is associated with father
involvement. We use data from the Fragile Families and Child Wellbeing Study to
examine how father involvement among relationship churners compares with father
involvement among those in three other relationship types (measured during the
first five years of the focal child's life): stably together relationships,
stably broken-up relationships, and repartnered relationships. First, we find
that churning fathers remain more involved with their 9-year-old children than do
parents who stably break up or repartner, but they are less involved than those
who are stably together. Second, lower relationship quality among churners-and,
to a lesser extent, repartnering and childbearing with a new partner-explains
some of the differences in father involvement between churners and the stably
together. Third, these differences are most apparent among parents not living
together when father involvement is measured. Taken together, the focus on
relationship churning extends prior research on the association between
relationship transitions and father involvement by separating relationship
instability from partner change.
PMID- 28425033
TI - Strengths and Limitations of Using the Polypill in Cardiovascular Prevention.
AB - PURPOSE OF REVIEW: Polypill and its role in cardiovascular disease (CVD)
prevention has been extensively discussed and debated since the inception of the
concept in 2003. This article reviews the subsequent accumulated research in this
area. RECENT FINDINGS: Several short and intermediate to long-term studies with
different brands of polypills have analysed the impact of polypill in phase II
and III trials. The strengths of polypill that have emerged include better
adherence, equivalent or better risk factor control and quality of life among
polypill users as compared to usual care. The lurking limitations include
difficulty with dose adjustment to targets, fear of mass medicalisation and low
acceptability among physicians. The current literature supports polypill use in
reducing blood pressure and cholesterol levels for CVD prevention with
improvement in adherence to medication. However, the long-term outcome of
polypill on CVD events and mortality are unavailable and are currently being
studied in clinical trials.
PMID- 28425035
TI - A new ascaridid nematode, Mammalakis zambiensis n. sp. (Heterakoidea:
Kiwinematidae), from the mole rat Fukomys anselli (Burda, Zima, Scharff, Macholan
& Kawalika) (Rodentia: Bathyergidae) in Zambia.
AB - Mammalakis zambiensis n. sp. is described from the large intestine and caecum of
Fukomys anselli (Burda, Zima, Scharff, Macholan & Kawalika), a bathyergid rodent
endemic to Zambia. Morphological data for comparison with its three congeners, M.
macrospiculum (Ortlepp, 1939), M. spalacis (Marcu, 1930) and M. spalaxi (Kozlov &
Jangolenko, 1962) are provided. Based on studies of the type-material,
observations of hitherto undescribed morphological characters of M.
macrospiculum, a parasite of Bathyergus suillus (Schreber) (Hystricomorpha:
Bathyergidae) in South Africa, are presented. To date, the generic diagnosis of
Mammalakis Inglis, 1991 is based largely on characters of its type-species, M.
macrospiculum. In having three rounded lips, not set-off from the body, a stout
oesophagus with a flask-shaped posterior bulb, lateral alae that broaden on the
level of the precloacal sucker and cloaca, and mature eggs with a smooth shell,
M. zambienis n. sp. corresponds to the characters of the genus. However, the
presence of lips with anterior flanges that were observed in M. zambiensis n.
sp., and also for the first time in M. macrospiculum, are in contrast with the
current diagnosis of Mammalakis. Further studies will be needed to determine if
an amendment of the generic diagnosis is indicated.
PMID- 28425034
TI - The molluscum contagiosum virus death effector domain containing protein MC160
RxDL motifs are not required for its known viral immune evasion functions.
AB - The molluscum contagiosum virus (MCV) uses a variety of immune evasion strategies
to antagonize host immune responses. Two MCV proteins, MC159 and MC160, contain
tandem death effector domains (DEDs). They are reported to inhibit innate immune
signaling events such as NF-kappaB and IRF3 activation, and apoptosis. The RxDL
motif of MC159 is required for inhibition of both apoptosis and NF-kappaB
activation. However, the role of the conserved RxDL motif in the MC160 DEDs
remained unknown. To answer this question, we performed alanine mutations to
neutralize the arginine and aspartate residues present in the MC160 RxDL in both
DED1 and DED2. These mutations were further modeled against the structure of the
MC159 protein. Surprisingly, the RxDL motif was not required for MC160's ability
to inhibit MAVS-induced IFNbeta activation. Further, unlike previous results with
the MC159 protein, mutations within the RxDL motif of MC160 had no effect on the
ability of MC160 to dampen TNF-alpha-induced NF-kappaB activation. Molecular
modeling predictions revealed no overall changes to the structure in the MC160
protein when the amino acids of both RxDL motifs were mutated to alanine (DED1 =
R67A D69A; DED2 = R160A D162A). Taken together, our results demonstrate that the
RxDL motifs present in the MC160 DEDs are not required for known functions of the
viral protein.
PMID- 28425036
TI - Lobocapillaria austropacifica n. g., n. sp. (Nematoda: Capillariidae) from the
obtuse barracuda Sphyraena obtusata Cuvier (Sphyraenidae, Perciformes) off
eastern Australia.
AB - Based on light and scanning electron microscopical studies, a new nematode
parasite, Lobocapillaria austropacifica n. sp. (Capillariidae), is described from
the gall-bladder of the marine fish (obtuse barracuda) Sphyraena obtusata Cuvier
(Perciformes: Sphyraenidae) from off the eastern Pacific coast of Australia, for
which a new genus Lobocapillaria n. g. is established. This new genus is mainly
characterised by a single row of stichocytes, the presence of two large,
conspicuously elongated lateral caudal lobes and a pair of subventral papillae at
their base in males, a flat spicule distended laterally towards its proximal end
and provided with superficial rough transverse grooves, a spicular canal and a
very long, aspinose spicular sheath with a conspicuous expansion near its
proximal end when evaginated. Capillaria sphyraeni Parukhin, 1971 is transferred
to Lobocapillaria as L. sphyreni (Parukhin, 1971) n. comb. A key to capillariid
genera containing species parasitic in fishes is provided.
PMID- 28425037
TI - A new species of Caryospora Leger, 1904 (Apicomplexa: Eimeriidae) from the
Guanabara spotted night snake Siphlophis pulcher (Raddi) (Reptilia: Dipsadidae)
in the Atlantic Forest, Brazil.
AB - A new coccidian species of the genus Caryospora Leger, 1904 (Apicomplexa,
Eimeriidae) is described based on material from the Guanabara spotted night snake
Siphlophis pulcher (Raddi) (Reptilia: Dipsadidae) in a coastal area of the
Atlantic Forest in Ilha Grande Island, state of Rio de Janeiro, southeastern
Brazil. Caryospora ceadsensis n. sp. possesses spheroidal to slightly
subspheroidal oocysts measuring 17-24 * 17-24 (22.1 * 22.0) um, with a c.1.3 um
thick bi-layered wall (inner layer smooth, outer layer slightly striated),
length/width (L/W) ratio of 1.0-1.1 (1.0) and a highly refractive polar granule.
Sporocysts are ellipsoidal, 11-17 * 10-13 (14.7 * 11.2) um, with a L/W ratio of
1.0-1.5 (1.3), with a nipple-like Stieda body (1.1 um high and 2.9 um wide) and a
large, bubble-shaped sub-Stieda body 1.7 um high and 3.8 um wide (1.0-2.0 * 3.0
4.5 um). Sporocyst residuum composed of granules of differing sizes. Sporozoites
with striations. This is the sixth record of a species of Caryospora in snakes of
the family Dipsadidae in Brazil.
PMID- 28425038
TI - A new species Selenonycha insperata n. sp. (Acariformes: Syringophilidae) from
the bare-faced ibis Phimosus infuscatus (Lichtenstein) (Pelecaniformes:
Threskiornithidae) as an example of host-switching event.
AB - A new quill mite species of the family Syringophilidae (Acariformes: Prostigmata:
Cheyletoidea) is described from Phimosus infuscatus (Lichtenstein)
(Pelecaniformes: Threskiornithidae) in Argentina. Selenonycha insperata n. sp.
differs from other species of the genus Selenonycha Kethley, 1970 by the presence
of wing-like cuticular projections of coxal fields III-IV situated in front of
trochanters (vs absence). An unexpected finding of this species on a bird of the
family Threskiornithidae (Pelecaniformes) is discussed as an example of host
shift. Additionally, a key to the species of the genus is provided.
PMID- 28425039
TI - Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual
Antiplatelet Therapy.
AB - Disaggregation as the difference between maximal and final platelet aggregation
by light transmission aggregometry indicates the stability of platelet
aggregates. We evaluated the extent of disaggregation after platelet stimulation
with adenosine diphosphate (ADP), arachidonic acid (AA), collagen, epinephrine,
and thrombin receptor-activating peptide (TRAP)-6 in 323 patients on dual
antiplatelet therapy with daily aspirin and clopidogrel (group 1), prasugrel
(group 2), or ticagrelor (group 3) therapy. All patients in group 1 underwent
elective angioplasty and stenting, whereas all patients included in groups 2 and
3 suffered from acute coronary syndromes (STEMI or NSTEMI) and underwent urgent
PCI. Significant differences between maximal and final platelet aggregation were
observed with all agonists throughout the groups (all p<0.001). Disaggregation
was highest using AA (clopidogrel 36.5%; prasugrel/ticagrelor 100%) and ADP
(clopidogrel 21.7%; prasugrel/ticagrelor 100%). In contrast, low disaggregation
was observed after platelet stimulation with collagen and TRAP-6 in clopidogrel
treated patients, and after platelet stimulation with collagen and epinephrine in
prasugrel- and ticagrelor-treated patients. In conclusion, pathways of platelet
activation that are not inhibited by standard antiplatelet therapy allow
persisting platelet aggregation and may at least in part be responsible for
adverse ischemic events.
PMID- 28425040
TI - Schiff base complexes of copper and zinc as potential anti-colitic compounds.
AB - The design, synthesis and activity of polymodal compounds for the treatment of
inflammatory bowel disease are reported. The compounds, being based on a metal
Schiff base motif, are designed to degrade during intestinal transit to release
the bioactive components in the gut. The compounds have been developed sequential
with the biomodal compounds combining copper or zinc with a salicylaldehyde
adduct. These compounds were tested in a formalin induced colonic inflammation
model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff
base analogue of sulfasalazine was designed. This was tested against a
trinitrobenzenesulfonic acid (TNB) induced colitic model in Wistar rats. The use
of two models allows us to test our compounds in both an acute and a chronic
model. The trimodal compound reported is observed to provide anticolitic
properties in the chronic TNB induced colitis model commensurate with that of
SASP. However, the design of trimodal compound still has the capacity for further
development. This the platform reported may offer a route into compounds which
can markedly outperform the anti-colitic properties of SASP.
PMID- 28425041
TI - Familial amyloid cardiomyopathy masquerading as chronic Guillain-Barre syndrome:
things are not always what they seem.
AB - Familial amyloid cardiomyopathy is a challenging condition that mimics many other
diseases, particularly in patients with pronounced neurological presentations and
unexplained or equivocal cardiac abnormalities. In this case, a 57-year-old man
was admitted for outpatient cardiological evaluation of progressive right heart
failure and limb paraesthesias. The patient presented with hypertension, chronic
Guillain-Barre syndrome, and sick sinus syndrome. Transthoracic echocardiograms
showed a thickened ventricular wall and enlarged atrium. Tissue Doppler showed a
restrictive filling pattern. Transthyretin (TTR)-associated amyloidosis, which
was revealed by abdominal fat-pad biopsy and DNA analysis, explained the
concurrence of independent pathological features, including neuropathy and
cardiac involvement. Genetic testing identified a G > T mutation in exon 4 of the
transthyretin (TTR) gene. This mutation resulted in the alanine-to-serine
substitution at amino acid position 117. Moreover, genetic testing confirmed that
the patient's asymptomatic son carried the same amyloidogenic TTR mutation. Given
these findings, the diagnosis of familial amyloid cardiomyopathy, which was
misdiagnosed as chronic Guillain-Barre syndrome, was proposed.
PMID- 28425042
TI - Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL
patient: a case report.
AB - Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic
sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined
with all-trans-retinotic acid (ATRA), ATO has become the first-line induction
therapy in treating acute promyelocytic leukemia (APL). The most common side
effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium
retention, and nervous system damage. In this report, we present a rare side
effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with
ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath,
myodynia, elevated creatine kinase, and acute renal insufficiency. This report
describes the first case of ATO-induced rhabdomyolysis.
PMID- 28425043
TI - Innovative development path of ethnomedicines: a case study.
AB - Innovative development extends the vitality of ethnomedicines. Developing
ethnomedicines is not only beneficial to the public but also to the related
industry and transforms economic growth, driving local social and economic
development further. Its economic benefit can be used to optimize and promote the
hardware and software of the platform, as well as support the sustainable
development of ethnomedicines. Apart from research and discussion on the
innovative development of ethnomedicines on the basis of theory and regulations,
this series of articles also summarizes cases that are conducive to the overall
understanding of the necessity and feasibility of the innovative development. In
terms of industrial development, large enterprises and products, such as Yunnan
Baiyao, Guizhou Miao ethnomedicines, Cheezheng Tibetan Medicine, products
developed from Dengzhanhua (Erigeron breviscapus), the Gold series of Yi
ethnomedicines, and products developed from Sanqi (Panax notoginseng), in China
are introduced and summarized, focusing on resource superiority, sustainable
innovation, standard research and development, and production, as well as
intellectual property protection.
PMID- 28425044
TI - Systematic review for geo-authentic Lonicerae Japonicae Flos.
AB - In traditional Chinese medicine, Lonicerae Japonicae Flos is commonly used as
anti-inflammatory, antiviral, and antipyretic herbal medicine, and geo-authentic
herbs are believed to present the highest quality among all samples from
different regions. To discuss the current situation and trend of geo-authentic
Lonicerae Japonicae Flos, we searched Chinese Biomedicine Literature Database,
Chinese Journal Full-text Database, Chinese Scientific Journal Full-text
Database, Cochrane Central Register of Controlled Trials, Wanfang, and PubMed. We
investigated all studies up to November 2015 pertaining to quality assessment,
discrimination, pharmacological effects, planting or processing, or ecological
system of geo-authentic Lonicerae Japonicae Flos. Sixty-five studies mainly
discussing about chemical fingerprint, component analysis, planting and
processing, discrimination between varieties, ecological system, pharmacological
effects, and safety were systematically reviewed. By analyzing these studies, we
found that the key points of geo-authentic Lonicerae Japonicae Flos research were
quality and application. Further studies should focus on improving the quality by
selecting the more superior of all varieties and evaluating clinical
effectiveness.
PMID- 28425045
TI - Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential
biomarker for the diagnosis of infectious diseases.
AB - Sensitive and useful biomarkers for the diagnosis and prognosis of infectious
diseases have been widely developed. An example of these biomarkers is triggering
receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor
expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation
by activating the TREM-1/DAP12 pathway. This pathway is triggered by the
interaction of TREM-1 with ligands or stimulation by bacterial
lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are
secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be
directly tested in human body fluids and well-known biomarker for infectious
diseases. sTREM-1 level can be potentially used for the early diagnosis and
prognosis prediction of some infectious diseases, including infectious pleural
effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g.,
Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g.,
Aspergillus infection), and burn-related infections. sTREM-1 is a more sensitive
and specific biomarker than traditional indices, such as C-reactive protein and
procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a
feasible biomarker for the targeted therapy and rapid and early diagnosis of
infectious diseases.
PMID- 28425046
TI - MiR-198 enhances temozolomide sensitivity in glioblastoma by targeting MGMT.
AB - Glioblastoma is one of the most frequent and aggressive brain tumors.
Accumulating evidence indicates that microRNAs are involved in glioma
proliferation, invasion and drug resistance. Previous studies showed that miR-198
is downregulated in glioblastoma. However, the function of miR-198 in
glioblastoma is still unclear. In this study, we report that miR-198 levels were
greatly downregulated in glioblastoma specimens and decreased expression of miR
198 was associated with poor prognosis in patients with glioblastoma. And
overexpression of miR-198 increased chemosensitivity to temozolomide in vitro and
in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct
target of miR-198, and miR-198 overexpression prevented the protein translation
of MGMT. Furthermore, overexpression of MGMT restored miR-198-induced
chemosensitivity to temozolomide. Moreover, the protein levels of MGMT were
upregulated in clinical glioblastoma specimens and inversely correlated with miR
198 levels. In conclusion, our studies revealed that MiR-198 induces
chemosensitivity in glioblastoma by targeting MGMT and that miR-198 may be used
as a new diagnostic marker and therapeutic target for glioblastoma in the future.
PMID- 28425047
TI - Can anti-vascular endothelial growth factor antibody reverse radiation necrosis?
A preclinical investigation.
AB - Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising
new treatment for late time-to-onset radiation-induced necrosis (RN). We sought
to evaluate and validate the response to anti-VEGF antibody in a mouse model of
RN. Mice were irradiated with the Leksell Gamma Knife PerfexionTM and then
treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN
progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR.
Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry
staining were used to validate the response to treatment. After treatment, both
post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased
(P < 0.001), while the lesion volumes for the control group increased. The
abnormally high apparent diffusion coefficient (ADC) for RN also returned to the
ADC range for normal brain following treatment (P < 0.001). However, typical RN
pathology was still present histologically. Large areas of focal calcification
were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia
inducible factor 1-alpha (HIF-1alpha) were continually upregulated in both the
anti-VEGF and control groups. Despite improvements observed radiographically
following anti-VEGF treatment, lesions were not completely resolved
histologically. The subsequent calcification and the continued upregulation of
VEGF and HIF-1alpha merit further preclinical/clinical investigation.
PMID- 28425049
TI - Erratum to: Successful Management of Zoon's Balanitis with Topical Mupirocin
Ointment: A Case Report and Literature Review of Mupirocin-Responsive Balanitis
Circumscripta Plasmacellularis.
PMID- 28425048
TI - Biopsy targeting with dynamic contrast-enhanced versus standard neuronavigation
MRI in glioma: a prospective double-blinded evaluation of selection benefits.
AB - Current biopsy planning based on contrast-enhanced T1W (CET1W) or FLAIR sequences
frequently delivers biopsy samples that are not in concordance with the gross
tumor diagnosis. This study investigates whether the quantitative information of
transfer constant Ktrans maps derived from T1W dynamic contrast-enhanced MRI (DCE
MRI) can help enhance the quality of biopsy target selection in glioma. 28
patients with suspected glioma received MRI including DCE-MRI and a standard
neuronavigation protocol of 3D FLAIR- and CET1W data sets (0.1 mmol/kg
gadobutrol) at 3.0 T. After exclusion of five cases with no Ktrans-elevation, 2-6
biopsy targets were independently selected by a neurosurgeon (samples based on
standard imaging) and a neuroradiologist (samples based on kinetic parameter
Ktrans) per case and tissue samples corresponding to these targets were collected
by a separate independent neurosurgeon. Standard technique and Ktrans-based
samples were rated for diagnostic concordance with the gross tumor resection
reference diagnosis (67 WHO IV; 24 WHO III and II) by a neuropathologist blinded
for selection mode. Ktrans-based sample targets differed from standard technique
sample targets in 90/91 cases. More Ktrans-based than standard imaging-based
samples could be extracted. Diagnoses from Ktrans-based samples were more
frequently concordant with the reference gross tumor diagnoses than those from
standard imaging-based samples (WHO IV: 30/39 vs. 11/20; p = 0.08; WHO III/II:
12/13 vs. 6/11; p = 0.06). In 4/5 non-contrast-enhancing gliomas, Ktrans-based
selection revealed significantly more accurate samples than standard technique
sample-selection (10/12 vs. 2/8 samples; p = 0.02). If Ktrans elevation is
present, Ktrans-based biopsy targeting provides significantly more diagnostic
tissue samples in non-contrast-enhancing glioma than selection based on CET1W and
FLAIR-weighted images alone.
PMID- 28425050
TI - Oxidative protein modification alters proteostasis under acute hypobaric hypoxia
in skeletal muscles: a comprehensive in vivo study.
AB - While numerous maladies are associated with hypobaric hypoxia, muscle protein
loss is an important under studied topic. Hence, the present study was designed
to investigate the mechanism of muscle protein loss at HH. SD rats were divided
into normoxic rats, while remaining rats were exposed to simulated hypoxia
equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at
25 degrees C for 6, 12, and 24 h. Post-exposure rats were sacrificed and
analysis was performed. Ergo, muscle loss-related changes were observed at 12 and
24 h post-HH exposure. An increased reactive oxygen species production and
decreased thiol content was observed in HH-exposed rats. This disturbance caused
substantial protein oxidative modification in the form of protein carbonyl
content and advanced oxidation protein products. The analysis showed increase
levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate
with MDA, protein hydroperoxide, and protein-MDA product. These changes were also
in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and
HSP-60 were upregulated significantly, and this finding is corroborated with
increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded
proteins further activated degradative machinery. Consequently, pro-apoptotic
signaling cascade, caspase-3, and C/EBP homologous protein were also activated in
24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h
HH exposure, indicated protein degradation. Elevation in resting intracellular
calcium ion, [Ca2+]i, was also observed at 12- and 24-h HH exposure. The present
study provides a detailed mechanistic representation of muscle protein loss
during HH exposure.
PMID- 28425051
TI - Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/alphaB-crystallin after
transient middle cerebral artery occlusion in rats.
AB - Ischemic stroke leads to cellular dysfunction, cell death, and devastating
clinical outcomes. The cells of the brain react to such a cellular stress by a
stress response with an upregulation of heat shock proteins resulting in
activation of endogenous neuroprotective capacities. Several members of the
family of small heat shock proteins (HspBs) have been shown to be
neuroprotective. However, yet no systematic study examined all HspBs during
cerebral ischemia. Here, we performed a comprehensive comparative study
comprising all HspBs in an animal model of stroke, i.e., 1 h transient middle
cerebral artery occlusion followed by 23 h of reperfusion. On the mRNA level out
of the 11 HspBs investigated, HspB1/Hsp25, HspB3, HspB4/alphaA-crystallin,
HspB5/alphaB-crystallin, HspB7/cvHsp, and HspB8/Hsp22 were significantly
upregulated in the peri-infarct region of the cerebral cortex of infarcted
hemispheres. HspB1 and HspB5 reached the highest mRNA levels and were also
upregulated at the protein level, suggesting that these HspBs might be
functionally most relevant. Interestingly, in the infarcted cortex, both HspB1
and HspB5 were mainly allocated to neurons and to a lesser extent to glial cells.
Additionally, both proteins were found to be phosphorylated in response to
ischemia. Our data suggest that among all HspBs, HspB1 and HspB5 might be most
important in the neuronal stress response to ischemia/reperfusion injury in the
brain and might be involved in neuroprotection.
PMID- 28425052
TI - DMSO Assisted Electrospray Ionization for the Detection of Small Peptide Hormones
in Urine by Dilute-and-Shoot-Liquid-Chromatography-High Resolution Mass
Spectrometry.
AB - The mobile phase additive (DMSO) has been described as a useful tool to enhance
electrospray ionization (ESI) of peptides and proteins. So far, this technique
has mainly been used in proteomic/peptide research, and its applicability in a
routine clinical laboratory setting (i.e., doping control analysis) has not been
described yet. This work provides a simple, easy to implement screening method
for the detection of doping relevant small peptides (GHRPs, GnRHs, GHS, and
vasopressin-analogues) with molecular weight less than 2 kDa applying DMSO in the
mobile phase. The gain in sensitivity was sufficient to inject the urine samples
after a 2-fold dilution step omitting a time consuming sample preparation. The
employed analytical procedure was validated for the qualitative determination of
36 compounds, including 13 metabolites. The detection limits (LODs) ranged
between 50 and 1000 pg/mL and were compliant with the 2 ng/mL minimum detection
level required by the World Anti-Doping Agency (WADA) for all the target
peptides. To demonstrate the feasibility of the work, urine samples obtained from
patients who have been treated with desmopressin or leuprolide and urine samples
that have been declared as adverse analytical findings were analyzed. Graphical
Abstract ?.
PMID- 28425053
TI - What Demographic and Clinical Characteristics Correlate With Expectations With
Trapeziometacarpal Arthritis?
AB - BACKGROUND: Pretreatment variables have been shown to be associated with the
fulfillment of patient expectations, yet in treating thumb trapeziometacarpal
osteoarthritis (OA) it remains unclear how patient expectations correlate with
the effectiveness of treatment. An increased understanding of the variables that
affect patient expectations enables tailored patient education and patient
provider communication. QUESTIONS/PURPOSES: (1) Is there a correlation between
patient demographics and clinical characteristics, and the expectations the
patients have when seeking treatment for trapeziometacarpal OA? (2) What factors
are independently associated with the total expectations score and frequency of
expecting "back to normal" among patients treated for trapeziometacarpal OA?
METHODS: Between March 2011 and October 2013, 89 patients of all 96 eligible
patients seeking treatment for trapeziometacarpal OA were approached and agreed
to participate in this study. Participants completed a validated expectations
survey measuring the number of expectations and the degree of improvement
expected. Comparative analysis of demographic and clinical characteristics and
multivariate regression analysis against patients' expectations were performed to
assess and identify factors that correlate with the number and degree of
expectations. Sample size was determined with an a priori power analysis (with
80% power and statistical significance set at p < 0.05), which showed that 88
patients were needed to detect the minimal clinical difference of 12 points in
the Michigan Hand Questionnaire; we then increased this by 10% to allow for
potential dropouts. RESULTS: After controlling for potential confounding
variables such as age, hand dominance, and work status, the following factors
were associated with a higher expectations score: choice of surgery (beta = 11.5;
95% CI, 0.7-23.8; p = 0.044), female gender (beta = 19.0; 95% CI, 5.3-32.7; p =
0.007), and dominant side affected (beta = -41.6; 95% CI, -63.7 to -19.5; p <
0.001). For the frequency of "back to normal" responses, surgical treatment (beta
= 7.4; 95% CI, 2.3-12.4; p = 0.005) and history of previous injury (beta = 8.2;
95% CI, 0.1-16.3; p = 0.047) were independently associated factors after
controlling for confounding variables. There were no independent associations
with age, marital status, work status, depression or anxiety, or prior
contralateral surgery. CONCLUSIONS: Patients whose dominant side was affected,
were female, and chose surgical treatment, had higher total expectations.
Patients who reported an antecedent injury and chose surgical treatment more
frequently expected a return to normal. With identification of these factors,
orthopaedic surgeons can recognize patients who are prone to higher expectations,
and, thus, have the opportunity to implement efficient pretreatment education. In
addition, identification of specific factors enables a focused measure of the
effect of these factors on the fulfillment of expectations. LEVEL OF EVIDENCE:
Level II, prognostic study.
PMID- 28425054
TI - Can a Three-Component Prosthesis be Used for Conversion of Painful Ankle
Arthrodesis to Total Ankle Replacement?
AB - BACKGROUND: In patients with painful ankle arthrodesis, the surgical treatment is
challenging, and may include takedown of ankle arthrodesis and conversion to a
total ankle replacement (TAR). This procedure is technically demanding given the
altered anatomy after arthrodesis. Few studies have evaluated TAR in the setting
of prior arthrodesis. QUESTIONS/PURPOSES: (1) What intraoperative and
perioperative complications were observed in patients who underwent conversion of
an ankle arthrodesis to a TAR? (2) Was durable fixation achieved at short term,
and what was the alignment of the components? (3) What subsequent surgical
procedures were performed, including revisions? (4) What improvements were
observed in pain, tibiotalar range of motion (ROM), and quality of life? METHODS:
Between January 2007 and December 2014, 18 patients with a painful ankle
arthrodesis underwent conversion to TAR at our tertiary referral center. During
this period, the indications for conversion of ankle arthrodesis to TAR were
tibiotalar nonunion or malunion after attempted arthrodesis in patients who
declined revision ankle arthrodesis. The goal of revision surgery was to help
patients regain hindfoot mobility and to decrease pain. During the study period,
all patients who met indications were treated with a conversion procedure. Of the
18 patients included, 14 were men and four were women. The mean age of the
patients was 51 +/- 7 years. The mean followup was 54 +/- 27 months, with no loss
to follow up observed. The initial ankle arthrodesis was performed 6 +/- 3.5
years before conversion to TAR. In all patients, the conversion to TAR was
performed using a nonconstrained cementless three-component prosthesis.
Intraoperative and postoperative complications, revision procedures, and
prosthesis component loosening were evaluated. Weightbearing radiographs were
used to determine the angular alignment of the tibial and talar components using
alpha/beta/gamma angles and to analyze the bone-implant interface.
Osseointegration was defined as visible trabecular structures at the bone-implant
interface without radiolucent lines. The criteria for radiographic loosening was
defined as subsidence or migration of prosthesis components and/or a cystic
lesion with a diameter at least 2 mm. Clinical assessment included pain
evaluation, measurement of ankle ROM, and quality of life. RESULTS: Two of the 18
patients sustained an intraoperative medial malleolar fracture. In three
patients, delayed wound healing was observed. At latest followup, four patients
had incomplete osseointegration (posterior quarter of the bone-prosthesis
interface on the tibial side). None of the 18 patients had prosthesis loosening.
In all patients, both components were neutrally aligned. Two patients had painful
arthrofibrosis with reduced ROM, which we treated with an open arthrolysis and
exchange of mobile-bearing inlay; one other patient is considering a revision for
substantial tibial component medial tilt with collapse of the medial arch. At the
latest followup, the mean dorsiflexion and plantar flexion were 8.5 degrees +/-
3 degrees and 15 degrees +/- 5 degrees , respectively. The mean visual analog
scale (VAS) score decreased from 9 +/- 0.8 to 1.7 +/- 1.6 (p < 0.001). The Short
Form Health Survey questionnaire (SF-36) physical and mental outcome scores
improved from 34 +/- 5 to 74 +/- 11 (p < 0.001) and from 49 +/- 4 to 75.5 +/- 7
(p < 0.001). CONCLUSIONS: Conversion of an ankle arthrodesis to a TAR is a
technically challenging procedure. In this small series, it was associated with
frequent complications including arthrofibrosis, and functional outcomes
including postoperative ROM were lower than reported for primary TAR. However,
pain and function did improve. Further studies are necessary to address long-term
clinical and radiographic outcomes in this patient cohort. LEVEL OF EVIDENCE:
Level IV, therapeutic study.
PMID- 28425055
TI - What are the Oncologic and Functional Outcomes After Joint Salvage Resections for
Juxtaarticular Osteosarcoma About the Knee?
AB - BACKGROUND: Joint salvage surgery for patients with juxtaarticular osteosarcoma
remains challenging, especially when the tumor invades the epiphysis. Because
patients are surviving longer with current chemotherapy regimens, it is
advantageous to retain native joints if possible, especially in young patients.
However, the results using joint-preserving tumor resections in this context have
not been well characterized. QUESTIONS/PURPOSES: (1) What are the functional
outcomes after limb salvage surgery at a minimum of 3 years? (2) What are the
oncologic outcomes? (3) Is joint salvage surgery for epiphyseal tumors associated
with an increased risk of local recurrence compared with metaphyseal tumors not
invading the epiphysis? (4) What are the complications associated with joint
salvage surgery? METHODS: Between 2004 and 2013, we treated 117 patients with
juxtaarticular osteosarcoma; of those, 43 (38%) were treated with joint salvage
surgery, and 41 (95%) of the 43 patients are included in our study. The other two
(5%) were lost to followup before 3 years (mean, 4.4 years; range, 3-11 years,).
During the period in question, we generally performed joint salvage surgery in
these patients when they had a favorable response to chemotherapy, did not have a
pathologic fracture or extrusion of the tumor into the joint, and did not have a
whole-epiphyseal osteolytic lesion, a large mass, or obvious neurovascular
involvement. This report is a followup of an earlier study; the current study
includes an additional nine patients, and additional followup of a mean of 19
months for the patients included in the earlier report. We ascertained overall
survival and survival free from local recurrence which was estimated using the
Kaplan-Meier method, functional status of the limb which was evaluated using the
Musculoskeletal Tumor Society (MSTS)-93 scoring system, and recorded
reconstructive complications including infection, fracture, skin necrosis, and
nonunion. We compared oncologic and functional outcomes between patients with (n
= 28) and without tumor extension to epiphysis (n =13). We also compared
oncologic and functional outcomes among patients with different adjuvant
treatments including microwave ablation (n = 11), cryoablation (n = 12), and
navigation-assisted osteotomy (n = 5). Complications were tallied using records
from our institutional database. RESULTS: The overall Kaplan-Mayer survival rate
was 82% (95% CI, 104-128 months) at 5 years. The overall Kaplan-Meier
survivorship from local recurrence was 91% at 5 years (95% CI, 115-133 months).
Three patients had a local recurrence, but none had local recurrence in or close
to the remaining epiphysis. The MSTS scores ranged from 22 to 30 points, with a
median of 28. There were no differences in survival rate, local recurrence, or
MSTS scores between patients with a tumor that did not invade the epiphysis and
those in whom the tumor did invade the epiphysis. There were differences in MSTS
scores among patients with epiphyseal tumor extension in which different adjuvant
techniques, including microwave ablation, cryoablation, and navigation-assisted
osteotomy, were used. Additional surgical procedures were recorded for 10
patients (24%). Osteonecrosis of the residual epiphysis was detected 13 patients
(31%). CONCLUSIONS: Our findings suggest it is possible to salvage joints in
selected patients with juxtaarticular osteosarcoma around the knee. The patients
who have a favorable response to chemotherapy are the best candidates for this
approach. Future studies might explore the role of adjuvant techniques of
microwave ablation and cryoablation, particularly when the tumor invades the
epiphysis, and whether resections can be facilitated with navigation. LEVEL OF
EVIDENCE: Level IV, therapeutic study.
PMID- 28425057
TI - Quantifying synergies in two-versus-one situations in team sports: An example
from Rugby Union.
AB - Collective behaviors in team sports result in players forming interpersonal
synergies that contribute to performance goals. Because of the huge amount of
variables that continuously constrain players' behavior during a game, the way
that these synergies are formed remain unclear. Our aim was to quantify
interpersonal synergies in the team sport of Rugby Union. For that purpose we
used the Uncontrolled Manifold Hypothesis (UCM) to identify interpersonal
synergies that are formed between ball carrier and support player in two-versus
one situations in Rugby Union. The inter-player angle close to the moment of the
pass was used as a performance variable and players running lines velocities as
task-relevant elements. Interpersonal synergies (UCM values above 1) were found
in 19 out of 55 trials under analysis, which means that on 34% of the trials, the
players' running line velocities contribute to stabilizing the inter-player angle
close the moment of the pass. The strength of the synergy fluctuates over time
indicating the existence of a location effect during attack phases in Rugby
Union. UCM analysis shows considerable promise as a performance analysis tool in
team sports to discriminate between skilled sub-groups of players.
PMID- 28425056
TI - Ischemic Heart Disease: Special Considerations in Cardio-Oncology.
AB - OPINION STATEMENT: The interplay and balance between the competing morbidity and
mortality of cardiovascular diseases and cancer have a significant impact on both
short- and long-term health outcomes of patients who survived cancer or are being
treated for cancer. Ischemic heart disease in patients with cancer or caused by
cancer therapy is a clinical problem of emerging importance. Prompt recognition
and optimum management of ischemic heart disease mean that patients with cancer
can successfully receive therapies to treat their malignancy and reduce morbidity
and mortality due to cardiovascular disease. In this sense, the presence of
cancer and cancer-related comorbidities (e.g., thrombocytopenia, propensity to
bleed, thrombotic status) substantially complicates the management of
cardiovascular diseases in cancer patients. In this review, we will summarize the
current state of knowledge on the management strategies for ischemic disease in
patients with cancer, focusing on the challenges encountered when addressing
these complexities.
PMID- 28425058
TI - Finding the traces of behavioral and cognitive processes in big data and
naturally occurring datasets.
AB - Today, people generate and store more data than ever before as they interact with
both real and virtual environments. These digital traces of behavior and
cognition offer cognitive scientists and psychologists an unprecedented
opportunity to test theories outside the laboratory. Despite general excitement
about big data and naturally occurring datasets among researchers, three "gaps"
stand in the way of their wider adoption in theory-driven research: the
imagination gap, the skills gap, and the culture gap. We outline an approach to
bridging these three gaps while respecting our responsibilities to the public as
participants in and consumers of the resulting research. To that end, we
introduce Data on the Mind ( http://www.dataonthemind.org ), a community-focused
initiative aimed at meeting the unprecedented challenges and opportunities of
theory-driven research with big data and naturally occurring datasets. We argue
that big data and naturally occurring datasets are most powerfully used to
supplement-not supplant-traditional experimental paradigms in order to understand
human behavior and cognition, and we highlight emerging ethical issues related to
the collection, sharing, and use of these powerful datasets.
PMID- 28425059
TI - GraphCom: A multidimensional measure of graphic complexity applied to 131 written
languages.
AB - We report a new multidimensional measure of visual complexity (GraphCom) that
captures variability in the complexity of graphs within and across writing
systems. We applied the measure to 131 written languages, allowing comparisons of
complexity and providing a basis for empirical testing of GraphCom. The measure
includes four dimensions whose value in capturing the different visual properties
of graphs had been demonstrated in prior reading research-(1) perimetric
complexity, sensitive to the ratio of a written form to its surrounding white
space (Pelli, Burns, Farell, & Moore-Page, 2006); (2) number of disconnected
components, sensitive to discontinuity (Gibson, 1969); (3) number of connected
points, sensitive to continuity (Lanthier, Risko, Stolz, & Besner, 2009); and (4)
number of simple features, sensitive to the strokes that compose graphs (Wu,
Zhou, & Shu, 1999). In our analysis of the complexity of 21,550 graphs, we (a)
determined the complexity variation across writing systems along each dimension,
(b) examined the relationships among complexity patterns within and across
writing systems, and (c) compared the dimensions in their abilities to
differentiate the graphs from different writing systems, in order to predict
human perceptual judgments (n = 180) of graphs with varying complexity. The
results from the computational and experimental comparisons showed that GraphCom
provides a measure of graphic complexity that exceeds previous measures in its
empirical validation. The measure can be universally applied across writing
systems, providing a research tool for studies of reading and writing.
PMID- 28425061
TI - Gray matter and white matter changes in non-demented amyotrophic lateral
sclerosis patients with or without cognitive impairment: A combined voxel-based
morphometry and tract-based spatial statistics whole-brain analysis.
AB - The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that
patients show structural changes within but also beyond the motor cortex and
corticospinal tract and furthermore outside the frontal lobes, even if frank
dementia is not detected. The aim of the present study was to investigate both
gray matter (GM) and white matter (WM) changes in non-demented amyotrophic
lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor
and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy
controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted
imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial
statistics analysis were performed to examine GM volume (GMV) changes and WM
differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD,
respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal
and cerebellar areas and increased GMV in right supplementary motor area, while
ALS-plus patients showed diffuse GMV reduction in primary motor cortex
bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor
patients had increased GMV in left precuneus compared to ALS-plus patients. We
also found decreased FA and increased RD in the corticospinal tract bilaterally,
the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased
FA and increased AD and RD in motor and several WM tracts in ALS-plus patients,
compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM
abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and
identifies early extra-motor brain pathology in ALS patients without cognitive
impairment (ALS-motor).
PMID- 28425060
TI - Positron emission tomography assessment of cerebral glucose metabolic rates in
autism spectrum disorder and schizophrenia.
AB - Several models have been proposed to account for observed overlaps in clinical
features and genetic predisposition between schizophrenia and autism spectrum
disorder. This study assessed similarities and differences in topological
patterns and vectors of glucose metabolism in both disorders in reference to
these models. Co-registered 18fluorodeoxyglucose PET and MRI scans were obtained
in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to
map cortical and subcortical regions of interest. Metabolic rates were compared
between three diagnostic groups using univariate and multivariate repeated
measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects
were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus,
amygdala and medial thalamic nuclei; rates were increased in the occipital
cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects
metabolic rates were decreased in the parietal lobe, frontal premotor and eye
fields areas, and amygdala; rates were increased in the posterior cingulate,
occipital cortex, hippocampus and basal ganglia. In relation to controls,
subjects with ASD and schizophrenia showed opposite changes in metabolic rates in
the primary motor and somatosensory cortex, anterior cingulate and hypothalamus;
similar changes were found in prefrontal and occipital cortices, inferior
parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD
appear to be associated with a similar pattern of metabolic abnormalities in the
social brain. Divergent maladaptive trade-offs, as postulated by the diametrical
hypothesis of their evolutionary relationship, may involve a more circumscribed
set of anterior cingulate, motor and somatosensory regions and the specific
cognitive functions they subserve.
PMID- 28425062
TI - Patients' Lived Experiences of Nocturia: A Qualitative Study of the Evening, the
Night, and the Next Day.
AB - BACKGROUND: Nocturia, waking to urinate two or more times during the night, is a
chronic condition associated with significant patient burden due to sleep
disruption. This study aimed to explore the lived experiences of patients with
nocturia in terms of the disruption to their lives during the night and day.
METHODS: Adult patients in the US diagnosed with nocturia were recruited for face
to-face qualitative interviews. Thematic analysis of patients' narratives, taking
a phenomenological interpretative approach, summarised their experiences
throughout the night and day, including any apparent contrasts between patients.
RESULTS: Twenty patients (10 male, 10 female) aged between 39 and 80 years,
averaging three night-time voids, were interviewed. Analysis revealed that
nocturia has a substantial impact on sleep quality and quantity, with the
frequency of night-time voids a key driver of this. In addition to night-time
phenomena, patients faced various difficulties the next day, including day-time
tiredness, lack of energy and concerns related to emotional wellbeing, social
functioning and cognitive functioning. All of these limited patients' capacity to
work, perform daily activities or fulfil role responsibilities. Patients'
lifestyles influenced experience, where younger patients in employment more
readily emphasised the day-time physical and psychosocial burdens. Patients
employed coping behaviours in an attempt to lessen the severity of nocturia and
its impact, which were both physician-led and self-taught. CONCLUSIONS: While the
symptom of nocturia only occurs during the night, the impact is longer lasting,
affecting functioning and wellbeing throughout the following day. Patients'
circumstances can affect the extent of their burden; recognising this can improve
effective delivery of patient-centred care.
PMID- 28425063
TI - Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and
Metabolism on Stem Cell Potency Loss and Miscarriage.
AB - Data from in vitro and in vivo models suggest that malnutrition and stress
trigger adaptive responses, leading to small for gestational age (SGA)
blastocysts with fewer cell numbers. These stress responses are initially
adaptive, but become maladaptive with increasing stress exposures. The common
stress responses of the blastocyst-derived stem cells, pluripotent embryonic and
multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased
growth and potency, and increased, imbalanced and irreversible differentiation.
SGA embryos may fail to produce sufficient antiluteolytic placental hormone to
maintain corpus luteum progesterone secretion that provides nutrition at the
implantation site. Myriad stress inputs for the stem cells in the embryo can
occur in vitro during in vitro fertilization/assisted reproductive technology
(IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead
to a higher level of differentiation simultaneously which further decreases ESC
or TSC numbers in an attempt to functionally compensate for fewer cells. In
addition, prolonged or strong stress can cause irreversible differentiation.
Resultant stem cell depletion is proposed as a cause of miscarriage via a "quiet"
death of an ostensibly adaptive response of stem cells instead of a reactive,
violent loss of stem cells or their differentiated progenies.
PMID- 28425065
TI - Changes in perfusion and diffusion in the endplate regions of degenerating
intervertebral discs: a DCE-MRI study.
PMID- 28425066
TI - Maverick total disc replacement in a real-world patient population: a
prospective, multicentre, observational study.
PMID- 28425067
TI - Answer to the Letter to the Editor of A. Agarwal et al. concerning "Rod fracture
lengthening intervals in traditional growing rods: is there a relationship?" by
P. Hosseini et al. Eur Spine J (2016); doi:10.1007/s00586-016-4786-8.
PMID- 28425064
TI - A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip
Platforms.
AB - Metastasis accounts for most cancer-related deaths. The majority of solid
cancers, including those of the breast, colorectum, prostate and skin,
metastasize at significant levels to the liver due to its hemodynamic as well as
tumor permissive microenvironmental properties. As this occurs prior to detection
and treatment of the primary tumor, we need to target liver metastases to improve
patients' outcomes. Animal models, while proven to be useful in mechanistic
studies, do not represent the heterogeneity of human population especially in
drug metabolism lack proper human cell-cell interactions, and this gap between
animals and humans results in costly and inefficient drug discovery. This
underscores the need to accurately model the human liver for disease studies and
drug development. Further, the occurrence of liver metastases is influenced by
the primary tumor type, sex and race; thus, modeling these specific settings will
facilitate the development of personalized/targeted medicine for each specific
group. We have adapted such all-human 3D ex vivo hepatic microphysiological
system (MPS) (a.k.a. liver-on-a-chip) to investigate human micrometastases. This
review focuses on the sources of liver resident cells, especially the iPS cell
derived hepatocytes, and examines some of the advantages and disadvantages of
these sources. In addition, this review also examines other potential challenges
and limitations in modeling human liver.
PMID- 28425068
TI - Analysis of cervical sagittal alignment change following correction of thoracic
and thoracolumbar Scheuermann's kyphosis.
AB - PURPOSE: To analyse pre-operative and post-operative changes of cervical sagittal
alignment (CSA) in Scheuermann's kyphosis (SK) patients. METHODS: 64 SK and 33
control patients were retrospectively reviewed. Whole spine X-rays obtained at
pre-op, 3 months post-op and at latest follow-up were reviewed and ten separate
CSA radiological parameters were measured. Patients were divided in three groups:
thoracic SK (TK group, apex T6-T9, n = 40), thoracolumbar SK (TLK group, apex T10
T12, n = 24), and controls. RESULTS: Pre-operative C2-C7 lordosis was 21.1
degrees +/- 8.1 degrees (TK), 6.1 degrees +/- 5.0 degrees (TLK), and 11.4
degrees +/- 8.3 degrees in control group and correlated significantly with T1
slope in both SK groups (r = 0.640, r = 0.772). Pre-operative T1 slope was
dependent on deformity type, thoracic kyphosis (TK, beta = 0.445), and lumbar
lordosis (LL, beta = -0.354). At final follow-up C2-C7 lordosis decreased to 15.7
degrees +/- 5.5 degrees in TK, and increased to 12.1 degrees +/- 4.1 degrees
in TLK group. C2-C7 lordosis changes linearly correlated with T1 slope changes
post-operatively (r = 0.721). Post-operative T1 slope showed linear correlation
with post-operative changes in TK (beta = 0.728) and pelvic tilt (PT, beta =
0.539) in TK, and LL (beta = -0.669), thoracolumbar kyphosis (TLK, beta =
0.434), and PT (beta = 0.760) in TLK group. CONCLUSIONS: Our study suggests that
SK is not a homogenous group of patients. Two patterns of pre- and post-operative
CSA are demonstrated in TK and TLK groups. T1 slope is the most important
parameter in determining pre-operative CSA and correlates with other regional
anatomical parameters (TK and LL). Post-operative CSA adaptations also correlate
with T1 slope post-operative changes. However, post-surgical T1 slope correlates
with different parameters in the two SK groups (TK and PT in TK group; TLK, LL,
and PT in TLK group).
PMID- 28425069
TI - A prospective serial MRI study following acute traumatic cervical spinal cord
injury.
AB - PURPOSE: In acute traumatic cervical spinal cord injury (SCI) patients, we sought
to characterize how objective MRI measures of injury change during the first 3
week post-injury. METHODS: Six MRI scans each were planned in 19 cervical SCI
patients within the first 3 week post-injury. Length of cord edema, maximum
spinal cord compression, maximum canal compromise, and presence and length of
hematoma were measured. RESULTS: Length of spinal cord edema increased in the
first 48 h after SCI, followed by a gradual decrease in the 3 weeks after injury.
This was predominantly seen in the more severe grades of SCI. Hematoma in the
spinal cord was seen in all AIS-A and B patients. CONCLUSION: This study
demonstrates the dynamic nature of imaging changes on MRI in the first weeks
after injury and highlights the importance of taking into account the timing of
imaging when interpreting objective measures of damage.
PMID- 28425070
TI - H emibagrus sp. as a potential bioindicator of hazardous metal pollution in
Selangor River.
AB - The spatial distributions of Na, Mg, K, Ca, Cr, Fe, Ni, Cu, Zn, As, Se and Pb in
Hemibagrus sp. from Selangor River and a reference site were determined with
inductively coupled plasma-mass spectrometer, in comparison to the levels in
their surrounding water body and sediments. The results demonstrated significant
differences in elemental accumulation pattern in different fish tissues
originated from both sites. The variations observed were mainly subjected to
their metabolic activities, and also the influence of the surrounding medium. In
general, the liver tends to accumulate higher concentration of metals followed by
the gills, and muscle tissues. The data also indicate associations between the
concentrations of metal contaminants measured in the fish and the levels observed
at the sites. The concentrations of hazardous metals As, Se and Pb in all the
studied tissues reflect the influence of anthropogenic inputs. This suggests the
potential utility of widely available Hemibagrus sp. as a valuable bioindicator
of metal pollution in environmental monitoring and assessment.
PMID- 28425071
TI - Micro-spatial variation of elemental distribution in estuarine sediment and their
accumulation in mangroves of Indian Sundarban.
AB - This work describes the micro-spatial variation of elemental distribution in
estuarine sediment and bioaccumulation of those elements in different mangrove
species of the Indian Sundarbans. The potential ecological risk due to such
elemental load on this mangrove-dominated habitat is also discussed. The
concentrations of elements in mangrove leaves and sediments were determined using
energy-dispersive X-ray fluorescence spectroscopy. Sediment quality and potential
ecological risks were assessed from the calculated indices. Our data reflects
higher concentration of elements, e.g., Al, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn,
and Pb, in the sediment, as compared to that reported by earlier workers.
Biological concentration factors for K, Ca, Mn, Fe, Cu, and Zn in different
mangroves indicated gradual elemental bioaccumulation in leaf tissues (0.002
1.442). Significant variation was observed for elements, e.g., Ni, Mn, and Ca, in
the sediments of all the sites, whereas in the plants, significant variation was
found for P, S, Cl, K, Ca, Mn, Fe, Cu, and Zn. This was mostly due to the
differences in uptake and accumulation potential of the plants. Various sediment
quality indices suggested the surface sediments to be moderately contaminated and
suffering from progressive deterioration. Cu, Cr, Zn, Mn, and Ni showed higher
enrichment factors (0.658-1.469), contamination factors (1.02-2.7), and geo
accumulation index (0.043-0.846) values. The potential ecological risk index
values considering Cu, Cr, Pb, and Zn were found to be within "low ecological
risk" category (20.04-24.01). However, Cr and Ni in the Sundarban mangroves
exceeded the effect range low and probable effect level limits. Strong
correlation of Zn with Fe and K was observed, reflecting their similar
transportation and accumulation process in both sediment and plant systems. The
plant-sediment elemental correlation was found to be highly non-linear,
suggesting role of some physiological and edaphic factors in the accumulation
process. Overall, the study of micro-spatial distribution of elements can act as
a useful tool for determining health of estuarine ecosystem.
PMID- 28425072
TI - Comment on: "Evaluation of Facebook and Twitter Monitoring to Detect Safety
Signals for Medical Products: An Analysis of Recent FDA Safety Alerts".
PMID- 28425073
TI - Molecular therapy of primary hyperoxaluria.
AB - During the last few decades, the molecular understanding of the mechanisms
involved in primary hyperoxalurias (PHs) has set the stage for novel therapeutic
approaches. The availability of PH mouse models has facilitated preclinical
studies testing innovative treatments. PHs are autosomal recessive diseases where
the enzymatic deficit plays a central pathogenic role. Thus, molecular therapies
aimed at restoring such deficit or limiting the consequences of the metabolic
derangement could be envisioned, keeping in mind the specific challenges posed by
the cell-autonomous nature of the deficiency. Various molecular approaches like
enzyme replacement, substrate reduction, pharmacologic chaperones, and gene and
cell therapies have been explored in cells and mouse models of disease. Some of
these proof-of-concept studies have paved the way to current clinical trials on
PH type 1, raising hopes that much needed treatments will become available for
this severe inborn error of metabolism.
PMID- 28425074
TI - LincRNa-p21: function and mechanism in cancer.
AB - In view of the rapid development of gene chips and high-throughput sequencing
technology, noncoding RNAs (ncRNas) form a high percentage of the mammalian
genome. Two major subgroups of ncRNAs that have been identified are the long
ncRNAs (lncRNas) and the microRNAs. A number of studies in the past few years
have showed crucial functions for lncRNas in cancer. LincRNa-p21 as a p53
dependent transcriptional target gene and a potential diagnostic marker is
involved in proliferation, cell cycle, metabolism and reprogramming. In addition,
more researches revealed that lincRNa-p21 is associated with cancer progression
and contributed to the treatment and prognosis of cancer. In this review, we
briefly summarize the function and molecular mechanisms of lincRNa-p21 in cancer
and its regulation for the genes expression .
PMID- 28425075
TI - Technical note: real-time web-based wireless visual guidance system for
radiotherapy.
AB - Describe a Web-based wireless visual guidance system that mitigates issues
associated with hard-wired audio-visual aided patient interactive motion
management systems that are cumbersome to use in routine clinical practice. Web
based wireless visual display duplicates an existing visual display of a
respiratory-motion management system for visual guidance. The visual display of
the existing system is sent to legacy Web clients over a private wireless
network, thereby allowing a wireless setting for real-time visual guidance. In
this study, active breathing coordinator (ABC) trace was used as an input for
visual display, which captured and transmitted to Web clients. Virtual reality
goggles require two (left and right eye view) images for visual display. We
investigated the performance of Web-based wireless visual guidance by quantifying
(1) the network latency of visual displays between an ABC computer display and
Web clients of a laptop, an iPad mini 2 and an iPhone 6, and (2) the frame rate
of visual display on the Web clients in frames per second (fps). The network
latency of visual display between the ABC computer and Web clients was about 100
ms and the frame rate was 14.0 fps (laptop), 9.2 fps (iPad mini 2) and 11.2 fps
(iPhone 6). In addition, visual display for virtual reality goggles was
successfully shown on the iPhone 6 with 100 ms and 11.2 fps. A high network
security was maintained by utilizing the private network configuration. This
study demonstrated that a Web-based wireless visual guidance can be a promising
technique for clinical motion management systems, which require real-time visual
display of their outputs. Based on the results of this study, our approach has
the potential to reduce clutter associated with wired-systems, reduce space
requirements, and extend the use of medical devices from static usage to
interactive and dynamic usage in a radiotherapy treatment vault.
PMID- 28425076
TI - Monoclonal gammopathy of renal significance (MGRS): the characteristics and
significance of a new meta-entity.
AB - Monoclonal gammopathy of renal significance (MGRS) is a new nosological group of
entities (meta-entity) defined in 2012, whose pathogenesis depends on monoclonal
immunoglobulins (Ig) secreted by low-grade lymphoproliferative disorders, which
belong to M-protein-related diseases. Renal damage is the result of monoclonal Ig
deposit or its activity as autoantibodies, which can compromise any nephronal
area. MGRS does not include kidney diseases produced by high-grade
lymphoproliferative disorders as well as those whose pathogenesis are independent
of monoclonal Ig (such as drug toxicity or metabolic disorders). The importance
of this hemato-nephrological meta-entity is based on two aspects: First, it is
associated with increased morbidity and mortality, including recurrence in post
renal transplant or its appearance as "de novo" after it; and second, it usually
improves after treating the plasmocyte or lymphocyte clone responsible, leading
to the elimination of M-protein. Between low-grade lymphoproliferative disorders,
monoclonal gammopathy of undetermined significance (MGUS) requires special
consideration for two reasons: First, it is the disorder most related to MGRS;
second, when MGUS progresses to MGRS, effective treatment against toxic underline
clone should be performed taking into account the nephrological perspective.
PMID- 28425077
TI - Unexpected and striking effect of heparin-free dialysis on cytokine release.
AB - Heparin (both unfractionated and low molecular weight) is not only a potent
anticoagulant but also has many pleiotropic effects, some of which are mediated
by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin
as an anticoagulant and without systemic anticoagulation (heparin-grafted
membrane-Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1),
endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed
with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured
after such a dialysis. During HD with Evodial, the intradialytic levels of all
three cytokines were 2-3 folds lower. The between-anticoagulant differences were
significant over time for all three cytokines: MCP-1 (P < 0.001), ES (P < 0.001)
and Act-A (P < 0.001). This striking effect of heparin-free dialysis with Evodial
membrane may be beneficial not only because it reduces the possibility of
bleeding complications but also because it might reduce proinflammatory cytokine
concentration and therefore contribute to the improvement in endothelial
function. Further studies are needed to determine whether it has a positive
effect on morbidity and mortality of maintenance HD patients.
PMID- 28425079
TI - Outcome of patients with septic shock and high-dose vasopressor therapy.
AB - BACKGROUND: Despite the dissemination of international guidelines, mortality from
septic shock remains high. Norepinephrine is recommended as first-line
vasopressor therapy with a target mean arterial pressure of 65 mmHg. High-dose
vasopressor (HDV) may also be required. This study aimed to assess survival in
patients with septic shock requiring HDV. We conducted a retrospective study of
patients admitted between January 2008 and December 2013 to a 13-bed ICU for
septic shock and receiving high-dose vasopressor therapy (defined by a dose >1
ug/kg/min). Primary outcome was 28-day mortality (D28). Secondary outcomes were
90-day mortality (D90), organ failure score (SOFA), duration of organ failure,
duration and dosage of vasopressor agent and ischemic complications. RESULTS: In
our cohort of 106 patients, mortality reached 60.4% at D28 and 66.3% at D90. One
in two patients died before D10. The weight-based mean dose of vasopressor (WMD)
represented the best prognostic factor. Using a cutoff of 0.75 ug/kg/min, WMD was
associated with mortality with a sensitivity of 73% and specificity of 74%. The
mortality rate reached 86.4% when WMD was above the cutoff value and associated
with a SOFA score >10. Digital or limb necrosis was documented in 6 patients
(5.7%). CONCLUSIONS: In total, 40% of septic shock patients receiving high-dose
vasopressor therapy survived at day 28 after admission. A WMD cutoff value of
0.75 ug/kg/min, associated with a >10 SOFA score, was a strong predictor of
death. These results provide insights into outcome of refractory septic shock,
showing that administration of high-dose vasopressor may indeed be useful in
these patients.
PMID- 28425080
TI - Monitoring of Paternal Mitochondrial Degradation in Caenorhabditis elegans.
AB - In Caenorhabditis elegans embryos, paternally inherited mitochondria and their
mitochondrial DNA are degraded via selective autophagy called allophagy
(allogeneic organelle autophagy). This is a developmentally programmed autophagy
and combined with C. elegans genetics and in vivo imaging provides a unique
opportunity to analyze selective autophagy under physiological conditions.
PMID- 28425078
TI - Involvement of interstitial cells of Cajal in bladder dysfunction in mice with
experimental autoimmune encephalomyelitis.
AB - BACKGROUND: Bladder dysfunction is an important symptom of experimental
autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced
upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4
(EP4) in the bladder was accompanied by bladder dysfunction. Although many other
studies have evaluated the lower urinary tract symptoms in multiple sclerosis,
the mechanism remains unclear. OBJECTIVES: To investigate the effects of
interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic
bladder model induced by experimental autoimmune encephalomyelitis. MATERIALS AND
METHODS: The EAE model was induced by a previously established method, and
bladder functions in mice were evaluated. Bladders were harvested for the
analysis of ICCs and the genes associated with bladder mechanosensation including
pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and
western blotting. The stem cell factor cytokine (SCF) was intraperitoneally
injected at the beginning of EAE onset. RESULTS: EAE mice developed profound
bladder dysfunction characterized by significant urine retention, increased
micturition and decreased urine output per micturition. EAE induced a significant
decrease in c-Kit expression and ICCs number. EAE also induced a significant
increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of
these pathological changes. CONCLUSIONS: ICCs and stem cell factor play an
important role in EAE-induced bladder dysfunction, which may be used as
therapeutic options in treating patients with multiple sclerosis-related bladder
dysfunction.
PMID- 28425081
TI - Perisinusoidal bone marrow involvement by lymphoma.
PMID- 28425082
TI - Discriminating between positional and non-positional obstructive sleep apnea
using some clinical characteristics.
AB - PURPOSE: The primary objective of this paper was to identify significant factors
associated with positional Obstructive Sleep Apnea (POSA) and to provide a
clinical tool for discriminating non positional from POSA. Secondary objectives
were about estimating the prevalence of POSA, comparing the polysomnographic
variables across POSA and non-POSA patients. METHODS: This was a cross sectional
study on 278 patients who completed an overnight sleep study for OSA assessment.
Patients were aged over 18 years, without central sleep apnea or narcolepsy and
slept no less than 20 min in a non-supine position. POSA was defined as a total
apnea/hypopnea index (AHI) >=5 and a ratio supine AHI/non-supine AHI >=2. The
binary logistic regression was used for modeling the likelihood for OSA patient
to be positional, and the LASSO method was used for selecting the optimal set of
clinical characteristics associated with POSA. RESULTS: Overall, 53% of patients
had POSA. These patients were younger (p = 0.005), had lower BMI (p < 0.0001),
lower prevalence of hypertension (p = 0.006), lower Berlin (p = 0.01), and lower
STOP (p = 0.001) scores compared to non-POSA patients. Neck and waist
circumference were higher in non-POSA (p = 0.005, p = 0.009, respectively)
patients. Age, BMI, DBP, Mallampati, and Berlin scores were found to be the best
clinical characteristics associated with POSA with an area under the ROC curve
(AUC) of 0.71 (95% CI [0.63, 0.78]). CONCLUSIONS: Half of patients referred for
the sleep study had POSA. Age, BMI, DBP, Mallampati, and Berlin scores, put
together, were shown to act as good clinical characteristics to discriminate
between POSA and non-POSA patients.
PMID- 28425083
TI - Restless legs syndrome/Willis-Ekbom disease prevalence in beta thalassemia
patients.
AB - PURPOSE: Both beta thalassemia and restless legs syndrome (RLS) patients share
some common pathophysiological characteristics related to iron handling. In the
present study, the aim was to explore the prevalence of RLS as well as to explore
potential association between the syndrome and various quality of life-related
parameters in a sample of beta thalassemia patients. METHODS: One hundred
fourteen (age 40 +/- 11 yr, 59 M/55F) beta thalassemia patients participated in
this cross-sectional descriptive study. Patients were screened for RLS based on
the international RLS study group diagnostic criteria as well as a battery of
validated questionnaires. RESULTS: The prevalence of RLS in this sample of beta
thalassemia patients was zero. The quality of life score was low (78 +/- 18).
Iron levels were within normal range (191 +/- 66 mcg/dL) while ferritin levels
were high as expected (1836 +/- 225 ng/dL). CONCLUSIONS: Our sample of patients
comes from central Greece where the prevalence of RLS in the general population
is 4% while in renal failure patients is 27%. To our surprise, there was no
presence of RLS among this sample of beta thalassemia patients. The adequate
levels of iron and ferritin often seen in these patients could be the reason of
the absence of RLS symptoms.
PMID- 28425084
TI - Independent dose verification for brain stereotactic radiotherapy using different
add-on micro multi-leaf collimators.
AB - An add-on micro multi-leaf collimator (mMLC) is used for stereotactic
radiosurgery (SRS) and brain stereotactic radiotherapy (SRT), in which rotational
radiotherapy may make more complex and time-consuming. We performed a
retrospective study of an independent dose calculation verification for brain SRS
and SRT in two institutions to show the accuracy of the verification system and
propose a tolerance value for the verification. Several comparisons of static
plans and patients' plans were conducted using a phantom measurement, and
patients' plans using the patients' own computed tomography image. We evaluated
the accuracy of the Clarkson-based dose calculation based on either the
equivalent square field formed by the mMLC or by the collimator jaws to determine
the collimator scatter factor (S c). The results for the static plans showed good
agreement (<1%), except when we used a 1 cm2 field size (<4%). The phantom
measurements for the patients' plans showed deviations of 0.1 +/- 2.3 and 1.2 +/-
1.6% (2 SD) for the treatment planning system and the verification system,
respectively. The patients' plans showed a deviation of 2.0 +/- 2.1% (2 SD).
Depending on the mMLC system, the S c was calculated using the equivalent field
size formed by the mMLC. In this study, we suggest a tolerance level for the
brain SRS and SRT of 2-3.5%. However, beam modeling in the treatment planning
system would affect the deviation. The S c should be computed according to the
size of the collimator fitted to the MLC.
PMID- 28425086
TI - The clinical benefits of denosumab for prophylaxis of steroid-induced
osteoporosis in patients with pulmonary disease.
AB - : Previous reports demonstrated that bone density decreased rapidly during the
initial few months of steroid therapy and continued decreasing at a rate of 2 to
4% annually. Our data indicates that denosumab can also play a role in the
treatment of osteoporosis in the steroid-taking population. INTRODUCTION:
Respiratory physicians are often faced with the dilemma that long-term steroid
use will deteriorate bone mineral density and quality. Previous reports
demonstrated that bone density decreased 8 to 12% during the initial few months
of steroid therapy then continued decreasing at a rate of 2 to 4% annually.
Several prospective trials revealed that denosumab increased bone density in
patients with osteoporosis [2-4] and decreased the rate of occurrence of
fractures. The long-term efficacy of denosumab for glucocorticoid-induced
osteoporosis, however, has not yet been proven. MATERIALS: This has been an
ongoing prospective study since 2014. In our respiratory centre, the first
preventative measure used to combat glucocorticoid-induced osteoporosis (GIO) is
oral bisphosphonates. Thirty-six patients were enlisted, and their treatment
courses were changed from oral bisphosphonate, if administered, to the
subcutaneous injection of denosumab 60 mg every 6 months, combined with a daily
oral intake of DENOTAS(r) chewable combination tablets. The primary efficacy
measures were changes in lumbar spine (LS) bone mineral density (BMD) and femoral
BMD from baseline at 4, 8, 12 and 28 months. RESULTS: At the 12-month follow-up,
bone mineral density in the lumbar spine area of these patients increased by
3.2%, while bone mineral density in the hip area showed no significant increase.
At the 28-month follow-up, 25 patients were still included in this study. Femoral
BMD at 28 months increased significantly from the 12-month follow-up (P =
0.0259), though the first 12 months showed no significant increase. LS BMD
continued to increase through the 28-month period. CONCLUSIONS: Very little is
known regarding the active prevention of GIO. Our data indicates that denosumab
can play a promising role in the treatment of GIO.
PMID- 28425088
TI - Commentary on: Zhou C, Byard RW. Septic ketoacidosis-a potentially lethal entity
with renal tubular epithelial vacuolization. J Forensic Sci 2017;62(1):122-5.
PMID- 28425087
TI - Peer Connect for African American breast cancer survivors and caregivers: a train
the-trainer approach for peer support.
AB - Racial disparities in breast cancer survivorship are a major concern nationally.
How survivors cope with cancer and re-frame their lives is a critical part of
survivorship. Community-academic research partnerships may facilitate access to
much-needed psychosocial support for African American survivors and caregivers in
rural areas, but drivers of successful intervention implementation are not well
understood. The purpose of this study was to describe the training and evaluation
of Community Coaches and Guides (i.e., peer supporters) using the Peer Connect
program for African American breast cancer survivors and caregivers. Community
engagement strategies were used to implement the training component of Peer
Connect, an evidence-based program grounded in the Diffusion of Innovation Theory
utilizing motivational interviewing techniques (MI) and a "train-the-trainer"
model. Quantitative and qualitative methods examined implementation outcomes of
feasibility, MI fidelity, and acceptability-precursor outcomes that must be
achieved before examining intervention impact vis-a-vis changes in support care.
Training was feasible to implement and replicable by the trained Community
Coaches. Beyond feasibility and replicability, success was modest regarding MI
fidelity. Benefits (e.g., serving as role models and having safe sources of
support) and lessons learned (e.g., need for additional quality control) were
identified as both facilitators and barriers to implementation and as factors
that could impact the effectiveness of community-engaged programs to improve
survivorship outcomes. Peer Connect, like other programs that employ community
engagement strategies, holds promise to meet the psychosocial support needs of
diverse rural cancer survivor populations.
PMID- 28425085
TI - UK clinical guideline for the prevention and treatment of osteoporosis.
AB - INTRODUCTION: In 2008, the UK National Osteoporosis Guideline Group (NOGG)
produced a guideline on the prevention and treatment of osteoporosis, with an
update in 2013. This paper presents a major update of the guideline, the scope of
which is to review the assessment and management of osteoporosis and the
prevention of fragility fractures in postmenopausal women and men age 50 years or
over. METHODS: Where available, systematic reviews, meta-analyses and randomised
controlled trials were used to provide the evidence base. Conclusions and
recommendations were systematically graded according to the strength of the
available evidence. RESULTS: Review of the evidence and recommendations are
provided for the diagnosis of osteoporosis, fracture-risk assessment, lifestyle
measures and pharmacological interventions, duration and monitoring of
bisphosphonate therapy, glucocorticoid-induced osteoporosis, osteoporosis in men,
postfracture care and intervention thresholds. CONCLUSION: The guideline, which
has received accreditation from the National Institute of Health and Care
Excellence (NICE), provides a comprehensive overview of the assessment and
management of osteoporosis for all healthcare professionals who are involved in
its management.
PMID- 28425089
TI - High diagnostic yield of clinically unidentifiable syndromic growth disorders by
targeted exome sequencing.
AB - BACKGROUND: As syndromic short stature and overgrowth are heterogeneous and the
list of causative genes is rapidly expanding, there is an unmet need for
identifying genetic causes based on conventional gene testing or karyotyping.
Early diagnosis leads to the proper management of the patient and providing
genetic counseling for family members at risk in a timely manner. MATERIALS AND
METHODS: We conducted targeted exome sequencing to identify the genetic causes of
undiagnosed syndromic short stature or overgrowth in 15 pediatric patients from
13 families in Korea. We applied targeted exome sequencing using the Next Seq
platform and a TruSight One panel. RESULTS: Among the 13 families, 6 different
disorders in 8 patients with short stature or overgrowth were identified, and the
diagnostic yield was 46.2%. One boy with overgrowth had a TGFB3 gene mutation. In
the short stature group, Coffin-Lowry syndrome (CLS), trichorhinophalangeal
syndrome, DYRK1A haploinsufficiency syndrome, short stature with optic atrophy
and Pelger-Huet anomaly syndrome with recurrent hepatitis, and type 4 Meier
Gorlin syndrome were identified. One CLS patient had a co-existing monogenic
disease, congenital glaucoma, caused by the compound heterozygote mutations of
the CYP1B1 gene. CONCLUSION: Targeted exome sequencing is a powerful method for
diagnosing syndromic growth disorders. It enables us to understand molecular
pathophysiology and investigate new treatments for growth disorders.
PMID- 28425090
TI - Determinants of the postpericardiotomy syndrome: a systematic review.
AB - BACKGROUND: Postpericardiotomy syndrome (PPS) is a common complication following
cardiac surgery; however, the exact pathogenesis remains uncertain. Identifying
risk factors of PPS might help to better understand the syndrome. The aim of this
study was to provide an overview of existing literature around determinants of
PPS in adult cardiac surgery patients. MATERIAL AND METHODS: Two independent
investigators performed a systematic search in MEDLINE, EMBASE and the Cochrane
Central Register. The search aimed to identify studies published between January
1950 and December 2015, in which determinants of PPS were reported. RESULTS: A
total of 19 studies met the selection criteria. In these studies, 14 different
definitions of PPS were used. The median incidence of PPS was 16%. After quality
assessment, seven studies were considered eligible for this review. Lower
preoperative interleukin-8 levels and higher postoperative complement conversion
products were associated with a higher risk of PPS. Among other clinical factors,
a lower age, transfusion of red blood cells and lower preoperative platelet and
haemoglobin levels were associated with a higher risk of PPS. Colchicine use
decreased the risk of PPS. CONCLUSION: We found that both the inflammatory
response and perioperative bleeding and coagulation may play a role in the
development of PPS, suggesting a multifactorial aetiology of the syndrome. Due to
a lack of a uniform definition of PPS in the past, study comparability was poor
across the studies.
PMID- 28425091
TI - Marine Bioluminescence: Measurement by a Classical Light Sensor and Related
Foraging Behavior of a Deep Diving Predator.
AB - Bioluminescence is produced by a broad range of organisms for defense, predation
or communication purposes. Southern elephant seal (SES) vision is adapted to low
intensity light with a peak sensitivity, matching the wavelength emitted by
myctophid species, one of the main preys of female SES. A total of 11 satellite
tracked female SESs were equipped with a time-depth-light 3D accelerometer (TDR10
X) to assess whether bioluminescence could be used by SESs to locate their prey.
Firstly, we demonstrated experimentally that the TDR10-X light sensor was
sensitive enough to detect natural bioluminescence; however, we highlighted a low
distance detection of the sensor. Then, we linked the number of prey capture
attempts (PCAs), assessed from accelerometer data, with the number of detected
bioluminescence events. PCA was positively related to bioluminescence, which
provides strong support that bioluminescence is involved in predator-prey
interactions for these species. However, the limitations of the sensor did not
allow us to discern whether bioluminescence (i) provided remote indication of the
biological richness of the area to SES, (ii) was emitted as a mechanic reaction
or (iii) was emitted as a defense mechanism in response to SES behavior.
PMID- 28425092
TI - Coffee consumption and the risk of colorectal cancer by anatomical subsite in
Japan: Results from the HERPACC studies.
AB - Consumption of coffee, a popular beverage worldwide, has been associated with
lower colorectal cancer (CRC) risk. Although CRC exhibits different biological
characteristics by anatomical subsite, the possibly heterogeneous impact of
coffee on CRC by anatomical subsite has remained unclear. Here, we conducted two
case-control studies to examine the association between coffee consumption and
CRC risk as well as risk by anatomic subsite among Japanese using data from the
Hospital-based Epidemiological Research Program at Aichi Cancer Center I and II
(HERPACC-I and II). Subjects were enrolled in HERPACC-I between 1988 and 2000 and
in HERPACC-II between 2001 and 2005. Coffee consumption was measured with a self
administered questionnaire. A conditional logistic regression model was used to
calculate odds ratios (ORs) of CRC with coffee consumption, adjusted for
potential confounders of age, smoking, alcohol drinking, red meat intake, BMI,
exercise, family history of CRC, and diabetes mellitus history. We estimated
summary ORs by pooling study-specific ORs with a fixed effects model. In total,
2,696 CRC cases and 13,480 non-cancer outpatients as controls were included.
Overall, compared to non-drinkers, ORs of less than 1 cup/day, 1-2 cups/day and 3
or more cups/day for CRC were 0.88 (95% CI: 0.77-1.00), 0.90 (95% CI: 0.80-1.01)
and 0.78 (95% CI: 0.65-0.92), respectively (trend-p = 0.009). Subsite-specific
analysis revealed a significant inverse linear trend between coffee consumption
and distal colon cancer (p-trend = 0.048), and a tendency toward a lower risk of
rectal cancer (p-trend = 0.068). These findings suggest that coffee consumption
might impact the prevention of CRC, especially distal colon cancer.
PMID- 28425093
TI - Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and
Meta-analysis.
AB - OBJECTIVES: To investigate whether low-dose aspirin (<300 mg/d) can influence the
onset of cognitive impairment or dementia in observational studies and improve
cognitive test scores in randomized controlled trials (RCTs) in participants
without dementia. DESIGN: Systematic review and meta-analysis. SETTING:
Observational and interventional studies. PARTICIPANTS: Individuals with no
dementia or cognitive impairment initially. MEASUREMENTS: Odds ratios (ORs) and
95% confidence intervals (CIs), adjusted for the maximum number of covariates
from each study, were used to summarize data on the incidence of dementia and
cognitive impairment in observational studies. Standardized mean differences
(SMDs) were used for cognitive test scores in RCTs. RESULTS: Of 2,341 potentially
eligible articles, eight studies were included and provided data for 36,196
participants without dementia or cognitive impairment at baseline (mean age 66,
63% female). After adjusting for a median of three potential confounders over a
median follow-up period of 6 years, chronic use of low-dose aspirin was not
associated with onset of dementia or cognitive impairment (5 studies, N = 26,159;
OR = 0.82, 95% CI = 0.55-1.22, P = .33, I2 = 67%). In three RCTs (N = 10,037;
median follow-up 5 years), the use of low-dose aspirin was not associated with
significantly better global cognition (SMD=0.005, 95% CI=-0.04-0.05, P = .84, I2
= 0%) in individuals without dementia. Adherence was lower in participants taking
aspirin than in controls, and the incidence of adverse events was higher.
CONCLUSION: This review found no evidence that low-dose aspirin buffers against
cognitive decline or dementia or improves cognitive test scores in RCTs.
PMID- 28425094
TI - Fatal Acute Hemorrhagic Bowel Infarction Caused by Mesenteric Venous Thrombosis.
AB - Acute mesenteric venous thrombosis (MVT) is a rare, but life-threatening medical
phenomenon. MVT is normally characterized by insidious onset, with nonspecific
signs and symptoms. A high index of clinical suspicion is required for diagnosis,
and emergency surgery is necessary to optimize the chances of patient survival,
especially in the people aged more than 70 years. Surprisingly, based on my
review of the literature, no fatal acute MVT case has been reported in the
forensic literature. All reported such cases have been documented in medical
literature, and most of them have been associated with underlying risk factors
for venous thrombosis, such as hypercoagulable state, certain cancers, and stasis
of the blood flow. Here, I report the case of a sudden unexpected death due to
extensive intestinal ischemia and infarction with massive abdominal hemorrhage
caused by acute MVT in a 72-year-old man without known underlying risk factors.
PMID- 28425095
TI - Psychomotor Tremor and Proprioceptive Control Problems in Current and Former
Stimulant Drug Users: An Accelerometer Study of Heavy Users of Amphetamine, MDMA,
and Other Recreational Stimulants.
AB - The recreational use of various stimulant drugs has been implicated in the
development of movement disorders through dysregulation of the dopaminergic and
serotoninergic neurotransmitter systems. The present study investigated
psychomotor differences in current and former recreational stimulant drug users
compared with nonusing controls. Sixty participants comprised 3 groups: 20
current stimulant drug users (CSUs; 11 men, aged 31.4 +/- 9.1 years), 20 former
stimulant drug users (FSUs; 5 men, aged 39.1 +/- 8.5 years), and 20 nonuser
controls (NUCs; 5 men, aged 35.7 +/- 6.4 years). Psychomotor arm steadiness for
each participant was assessed with a wrist-attached accelerometer during 5 arm
positions with eyes open and then eyes closed. Arm-drop of arm position was
indicated by the arm longitudinal rotation axis (ALoRA), and tremor was indicated
by the overall vector of dynamic body acceleration (VeDBA). Overall, CSUs
performed the most poorly on ALoRA (P < .05) and VeDBA indices (P < .05), and
FSUs perform almost as poorly on VeDBA indices (P < .05) compared with NUCs. It
was concluded that stimulant drug use, primarily MDMA and amphetamines, may
result in acute stimulant-induced tremor as well as long-term proprioceptive
deficits in terms of arm-droop.
PMID- 28425096
TI - Influence of coral cover and structural complexity on the accuracy of visual
surveys of coral-reef fish communities.
AB - Using manipulated patch reefs with combinations of varying live-coral cover (low,
medium and high) and structural complexity (low and high), common community
metrics (abundance, diversity, richness and community composition) collected
through standard underwater visual census techniques were compared with
exhaustive collections using a fish anaesthetic (clove oil). This study showed
that reef condition did not influence underwater visual census estimates at a
community level, but reef condition can influence the detectability of some small
and cryptic species and this may be exacerbated if surveys are conducted on a
larger scale.
PMID- 28425098
TI - Authors' Response.
PMID- 28425099
TI - Network analysis of adhesion/growth-regulatory galectins and their binding sites
in adult chicken retina and choroid.
AB - The highly ordered multilayered organization of the adult chicken retina is a
suitable test model for examining zonal distribution of the members of a
bioeffector family. Based on the concept of the sugar code, the functional
pairing of glycan epitopes with cognate receptors (lectins) is emerging as a
means to explain the control of diverse physiological activities. Having recently
completed the biochemical characterization of all seven adhesion/growth
regulatory galectins present in chicken, it was possible to establish how the
individual characteristics of their expression profiles add up to shape the
galectin network, which until now has not been defined at this level of
complexity. This information will also have relevance in explaining the region
specific presence of glycan determinants in the retina, as illustrated in the
first part of this study using a panel of nine plant/fungal agglutinins. The
following systematic monitoring of the galectins yielded patterns for which
quantitative and qualitative differences were detected. Obviously, positivity in
distinct layers is not confined to a single protein of this family, e.g. CG-1A,
CG-3 or CG-8. These results underline the requirement for network analysis for
these proteins that can functionally interact in additive or antagonistic modes.
Labeling of the tissue galectins facilitated profiling of their accessible
binding sites. It also revealed differences among the galectin family members,
highlighting the ability of this method to define binding properties on the level
of tissue sections. Methodologically, the detection of endogenous lectins
intimates that cognate glycans can become inaccessible, a notable caveat for
lectin histochemical studies.
PMID- 28425097
TI - Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a
mouse model of temporal lobe epilepsy.
AB - Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be
difficult to treat effectively. It can develop after brain injuries that damage
the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal
dentate gyrus have been proposed. This study evaluated a mouse model of temporal
lobe epilepsy to test which pathological changes in the dentate gyrus correlate
with seizure frequency and help prioritize potential mechanisms for further
study. FVB mice (n = 127) that had experienced status epilepticus after systemic
treatment with pilocarpine 31-61 days earlier were video-monitored for
spontaneous, convulsive seizures 9 hr/day every day for 24-36 days. Over 4,060
seizures were observed. Seizure frequency ranged from an average of one every 3.6
days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain,
Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial
fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in
situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods
were used to measure hilar ectopic granule cells, mossy cells, mossy fiber
sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not
significantly correlated with the generation of hilar ectopic granule cells, the
number of mossy cells, the extent of mossy fiber sprouting, the extent of
astrogliosis, or the number of GABAergic interneurons in the molecular layer or
hilus. Seizure frequency significantly correlated with the loss of GABAergic
interneurons in or adjacent to the granule cell layer, but not with the loss of
parvalbumin-positive interneurons. These findings prioritize the loss of granule
cell layer interneurons for further testing as a potential cause of temporal lobe
epilepsy.
PMID- 28425100
TI - Mass spectrometry analysis and in silico prediction of allergenicity of peptides
in tryptic hydrolysates of the proteins from Ruditapes philippinarum.
AB - BACKGROUND: Ruditapes philippinarum is nutrient-rich and widely-distributed, but
little attention has been paid to the identification and characterization of the
bioactive peptides in the bivalve. In the present study, we evaluated the
peptides of the R. philippinarum that were enzymolysised by trypsin using a
combination of ultra-performance liquid chromatography separation and
electrospray ionization quadrupole time-of-flight tandem mass spectrometry,
followed by data processing and sequence-similarity database searching. The
potential allergenicity of the peptides was assessed in silico. RESULTS: The
enzymolysis was performed under the conditions: E:S 3:100 (w/w), pH 9.0, 45
degrees C for 4 h. After separation and detection, the Swiss-Prot database and a
Ruditapes philippinarum sequence database were used: 966 unique peptides were
identified by non-error tolerant database searching; 173 peptides matching 55
precursor proteins comprised highly conserved cytoskeleton proteins. The
remaining 793 peptides were identified from the R. philippinarum sequence
database. The results showed that 510 peptides were labeled as allergens and 31
peptides were potential allergens; 425 peptides were predicted to be
nonallergenic. CONCLUSION: The abundant peptide information contributes to
further investigations of the structure and potential function of R.
philippinarum. Additional in vitro studies are required to demonstrate and ensure
the correct production of the hydrolysates for use in the food industry with
respect to R. philippinarum. (c) 2017 Society of Chemical Industry.
PMID- 28425102
TI - Fatal Overdose of Gamma-hydroxybutyrate Acid After Ingestion of 1,4-Butanediol.
AB - We report a case of fatal intoxication from 1,4-butanediol (1,4-BD), which was
ingested by a young and "naive" gamma-hydroxybutyrate (GHB) consumer during a
party with the co-ingestion of alcohol, cannabis, and methylene-dioxy
methamphetamine. The following drug concentrations were found using gas
chromatography coupled with mass spectrometry on autopsy samples and on a cup and
a glass found at the scene: 20,350 mg/L (bottle) for 1,4-BD; 1020 mg/L (femoral
blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L
(vitreous humor) for GHB. The concentration of GHB is difficult to interpret in
forensic cases due to the possibility of an endogenous production of GHB. The
variable tolerance of the user may also modify the peri- and postmortem GHB
concentrations. This case underscores the need to have many different sources of
toxicology samples analyzed to avoid the hypothesis of endogenous production of
GHB.
PMID- 28425103
TI - Remains of care: opioid substitution treatment in the post-welfare state.
AB - This article examines how the amplified role of pharmaceutical substances in
addiction treatment affects the everyday realisation of care, particularly the
relationship between workers and patients, in so called austere environments.
Theoretically the article draws firstly on the literature that links
pharmaceuticalisation to the neoliberal undoing of central public structures and
institutions of care, and secondly on Anne-Marie Mol's concept of the logic of
care. Based on an ethnographic analysis of the everyday life at a Finnish opioid
substitution treatment clinic we show the mechanisms through which the
realisation of pharmacotherapy can, in the current political climate, result in a
very narrow understanding of drug problems and minimal human contact between
patients and professionals. Our analysis manifests an important shift in the
logic of addiction treatment and health-care policy more broadly; namely, a
growing tendency to emphasise the need for patients to care for themselves and
make good choices with limited help from formal care institutions and
professionals. We call this new ethos the logic of austerity.
PMID- 28425104
TI - Inactivation kinetics and residual activity of CYP3A4 after treatment with
erythromycin.
AB - This study aimed to characterize the inactivation kinetics of cytochrome P450 3A4
(CYP3A4) by erythromycin, which involves mechanism-based inhibition (MBI), in
detail. In addition to an MBI assay based on the conventional method in which
erythromycin and recombinant CYP3A4 were pre-incubated for 15 min, the study also
evaluated the long-term MBI kinetics of this reaction by pre-incubation for 120
min. Mechanism-based inhibition profiles were obtained using three typical
substrates, testosterone, midazolam and nifedipine. In the long-term assay,
erythromycin evoked a time-dependent biphasic reduction in enzyme activity, but
some residual activity (alpha) was detected in the terminal phase. The
inactivation rate constant obtained in the presence of 30 MUm erythromycin using
nifedipine as a substrate was 1.44-fold higher than that acquired using
testosterone, while there was no difference among the alpha values obtained with
the three substrates. In the short-term assay, time-dependent monophasic
inactivation was observed. To extrapolate these data to in vivo, the extent of
the increase in the area under the curve (AUC ratio) induced by erythromycin was
estimated from the results of the conventional short-term experiment and the long
term experiment examining residual activity. The AUC ratio estimated from the
long-term kinetics (2.92) was closer to the clinically reported values (3.3
4.42). In conclusion, the relatively long-term evaluation of the kinetics of
CYP3A4 inactivation revealed that the enzyme was not fully inactivated by
erythromycin. To improve the estimation of the extent of the drug-drug
interactions induced by MBI from in vitro data, longer-term investigations of the
target enzyme's inactivation profile might be necessary.
PMID- 28425105
TI - The incidence of anterior pituitary hormone deficiencies in patients with
microprolactinoma and idiopathic hyperprolactinaemia.
AB - INTRODUCTION: Patients with microprolactinoma and idiopathic hyperprolactinaemia
are not generally considered to be at risk of hypopituitarism and are therefore
not routinely screened for this abnormality. In our clinical practice, we have
observed a number of patients with nonmacroadenomatous hyperprolactinaemia to
have anterior pituitary hormone deficits. AIMS: We aimed to establish the
frequency and clinical significance of anterior pituitary hormone deficiencies,
comparing patients with radiologically proven microprolactinomas and patients
with idiopathic hyperprolactinaemia. STUDY DESIGN: We retrospectively examined
the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients
who did not fit the profile of surgically naive microprolactinoma or idiopathic
hyperprolactinaemia or who had incomplete data were excluded, resulting in a
study group of 56 patients. RESULTS: A total of 35 patients with MRI evidence of
microprolactinoma were identified, three (8.57%) of whom had one or more anterior
pituitary hormone deficiencies. A total of 21 patients with MRI-negative
idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or
more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI
positive group had deficiency that required hormone replacement, in contrast six
patients in the MRI-negative group had deficiencies that were of clinical
significance and which required hormone replacement. SUMMARY: This study shows a
clinically significant incidence of anterior pituitary hormone deficiency in
patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic
pituitary assessment should be considered routinely in this patient group. A
prospective study would be required to assess the underlying cause for these
abnormalities, as they suggest a nontumour pan-pituitary process.
PMID- 28425106
TI - The concept of medicalisation reassessed: a response to Joan Busfield.
PMID- 28425107
TI - Metastatic Urothelial Carcinoma Presenting as Carcinoma Erysipeloides.
PMID- 28425108
TI - Coexistence of psoriasis and epidermolysis bullosa acquisita: Evaluation of the
integrity of the basement membrane.
PMID- 28425109
TI - Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte
Contractility.
AB - Alcoholic cardiomyopathy (ACM) can develop after consumption of relatively large
amounts of alcohol over time or from acute binge drinking. Of the many factors
implicated in the etiology of ACM, chronic perturbation in protein balance has
been strongly implicated. This review focused on recent contributions (since
2010) in the area of protein metabolism and cardiac function related to ACM. Data
reviewed include that from in vitro and preclinical in vivo animal studies where
alcohol or an oxidative metabolite was studied and outcome measures in either
cardiomyocytes or whole heart pertaining to protein synthesis or degradation were
reported. Additionally, studies on the contractile properties of cardiomyocytes
were also included to link signal transduction with function. Methodological
differences including the potential impact of sex, dosing, and duration/timing of
alcohol administration are addressed. Acute and chronic alcohol consumption
decreases cardiac protein synthesis and/or activation of proteins within the
regulatory mammalian/mechanistic target of rapamycin complex pathway. Albeit
limited, evidence suggests that myocardial protein degradation via the ubiquitin
pathway is not altered, while autophagy may be enhanced in ACM. Alcohol impairs
ex vivo cardiomyocyte contractility in relation to its metabolism and expression
of proteins within the growth factor pathway. Dysregulation of protein
metabolism, including the rate of protein synthesis and autophagy, may contribute
to contractile deficits and is a hallmark feature of ACM meriting additional sex
inclusive, methodologically consistent studies.
PMID- 28425110
TI - Neural tube defects: Risk factors and preventive measures.
AB - For the last 25 years, it has been proven that the occurrence or recurrence of
neural tube defects can be prevented with the administration of folic acid before
and early pregnancy. At present, over 80 countries in the world, except Japan,
have mandated the fortification of wheat flour and/or rice with folic acid, which
has resulted in a significant reduction in the prevalence of neural tube defects.
In 2000, the Japanese government recommended folic acid 400 MUg daily for young
women of childbearing age and women who are planning to conceive. In 2002, the
government started to present information about the importance of folic acid in
the development of fetuses in the Mother-Child Health Booklet annually. Despite
these endeavors, the prevalence of neural tube defects has remained unchanged. We
discuss the risk factors of neural tube defects and propose preventive measures
to decrease the number of neonates with neural tube defects. We believe that the
government should implement the fortification of staple food with folic acid very
soon, which will eventually decrease not only the neonatal mortality and
morbidity, but also the economic burden on our health care system.
PMID- 28425111
TI - "Nails Only" Phenotype and Partial Dominance of p.Glu170Lys Mutation in a Family
with Epidermolysis Bullosa Simplex.
AB - Epidermolysis bullosa (EB) is a heterogeneous group of rare, chronic, inherited
skin disorders characterized by marked mechanical fragility of epithelial
tissues, with blistering and erosions after minor trauma. We present the first
report of a nails-only phenotype in two patients with epidermolysis bullosa
simplex (EBS) and a heterozygous pGlu170Lys mutation and the second reported case
of EBS associated with a homozygous p.Glu170Lys mutation in the KRT5 gene. Our
findings may be relevant for genetic counseling and for understanding the
inheritance pattern of EBS.
PMID- 28425112
TI - Beyond guidelines: discretionary practice in face-to-face triage nursing.
AB - This article draws on ethnographic data from a Norwegian emergency primary care
clinic (EPCC) to explore nurses' discretionary application of guidelines.
Specifically, it analyses nurses' discretionary use of the Manchester Triage
System (MTS) when performing face-to-face triage, that is, assessing the urgency
of patients' complaints. The analysis shows how nurses assessed patients at odds
with MTS prescriptions by collecting supplementary data, engaging in differential
diagnostic and holistic reasoning, relying on emotion and intuition, and allowing
colleagues and patients to influence their reasoning. The findings also show how
nurses' reasoning led them to override guidelines both overtly and covertly.
Based on this evidence, it is argued that nurses' assessments relied more on
internalised 'triage mindlines' than on codified triage guidelines, although the
MTS did function as a support system, checklist and system for supervisory
control. The study complements existing research on standardisation in nursing by
providing an in-depth analysis of nurses' methods for navigating guidelines and
by detailing how deviations from those guidelines spring from their clinical
reasoning. The challenges of imposing a managerial logic on professional labour
are also highlighted, which is of particular relevance in light of the drive
towards standardisation in modern healthcare.
PMID- 28425113
TI - Environmental perfluorooctane sulfonate exposure drives T cell activation in
bottlenose dolphins.
AB - Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been
associated with immunotoxicity in epidemiologic studies and experimental rodent
models. Lengthy half-lives and resistance to environmental degradation result in
bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate
(PFOS), the most prevalent PFAA detected within the environment, is found at high
levels in occupationally exposed humans. We have monitored the environmental
exposure of dolphins in the Charleston, SC region for over 10 years and levels of
PFAAs, and PFOS in particular, were significantly elevated. As dolphins may serve
as large mammal sentinels to identify the impact of environmental chemical
exposure on human disease, we sought to assess the effect of environmental PFAAs
on the cellular immune system in highly exposed dolphins. Herein, we utilized a
novel flow cytometry-based assay to examine T cell-specific responses to
environmental PFAA exposure ex vivo and to exogenous PFOS exposure in vitro.
Baseline PFOS concentrations were associated with significantly increased CD4+
and CD8+ T cell proliferation from a heterogeneous resident dolphin population.
Further analysis demonstrated that in vitro exposure to environmentally relevant
levels of PFOS promoted proinflammatory cytokine production and proliferation in
a dose-dependent manner. Collectively, these findings indicate that PFOS is
capable of inducing proinflammatory interferon-gamma, but not immunoregulatory
interleukin-4 production in T cells, which may establish a state of chronic
immune activation known to be associated with susceptibility to disease. These
findings suggest that PFOS directly dysregulates the dolphin cellular immune
system and has implications for health hazards. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28425114
TI - A multi-institutional joint study of contact dermatitis related to hair colouring
and perming agents in Japan.
AB - BACKGROUND: In Japan, allergic contact dermatitis caused by hair colouring agents
is a considerable problem for those occupationally exposed and also for
consumers. Over the last 20 years, p-phenylenediamine (PPD) has been a common
allergen, with ~7% positive patch test reactions. OBJECTIVES: To investigate
which ingredients caused allergic contact dermatitis related to hair dye and
perming solutions in Japan, to assess whether PPD is suitable for screening for
hair dye allergy, and to propose allergens for a Japanese hairdresser series.
METHODS: We selected 19 hair cosmetic allergens, including PPD, Bandrowski's
base, cysteamine HCl, and ammonium thioglycolate. Altogether 203 patients (26
males and 177 females) with suspected contact allergy to hair colouring or
perming solutions at 14 hospitals in Japan were included. RESULTS: The highest
prevalence of positive reactions (35.1%) was for PPD. p-Methylaminophenol and o
aminophenol were often positive, both in the PPD-positive and in the PPD-negative
patients. Moreover, cysteamine HCl often yielded positive test reactions.
CONCLUSIONS: PPD is insufficient to diagnose contact allergy caused by to hair
dyes. We recommend 13 allergens to be included in a Japanese hairdresser series.
PMID- 28425115
TI - 'It seems like you're going around in circles': recurrent biographical disruption
constructed through the past, present and anticipated future in the narratives of
young adults with inflammatory bowel disease.
AB - Biographical disruption and related concepts continue to be widely drawn upon in
explaining how individuals experience chronic illness. Through in-depth
examination of the narrative experiences of two young adults with inflammatory
bowel disease (IBD), this article aims to contribute to the continuing
theoretical elaboration of biographical disruption, and in turn offer new
insights into how young adults experience this condition. The cases are analysed
from an interaction-based, constructionist perspective, through which it is
argued that the relapse-remission nature of IBD can give rise to a particular
form of recurrent biographical disruption, constructed in narrative through a
complex configuration of past, present and anticipated future experiences. The
two young adults are found to give different meaning to this recurrent disruption
in terms of its significance and consequences - whilst Samuel represents an
ongoing cycle of profound disruption and biographical reinstatement, Edith
normalises the cycle of disruption and its role in her ongoing biography.
Therefore, moving beyond the notion of 'normal illness' observed in previous
research literature, the concept of 'normal recurrent disruption' is proposed.
Finally, it is argued that this recurrent biographical disruption may be
experienced particularly severely in young adulthood owing to the unique
pressures and expectations of this lifestage.
PMID- 28425116
TI - Dynamic probability control limits for risk-adjusted CUSUM charts based on
multiresponses.
AB - For a patient who has survived a surgery, there could be several levels of
recovery. Thus, it is reasonable to consider more than two outcomes when
monitoring surgical outcome quality. The risk-adjusted cumulative sum (CUSUM)
chart based on multiresponses has been developed for monitoring a surgical
process with three or more outcomes. However, there is a significant effect of
varying risk distributions on the in-control performance of the chart when
constant control limits are applied. To overcome this disadvantage, we apply the
dynamic probability control limits to the risk-adjusted CUSUM charts for
multiresponses. The simulation results demonstrate that the in-control
performance of the charts with dynamic probability control limits can be
controlled for different patient populations because these limits are determined
for each specific sequence of patients. Thus, the use of dynamic probability
control limits for risk-adjusted CUSUM charts based on multiresponses allows each
chart to be designed for the corresponding patient sequence of a surgeon or a
hospital and therefore does not require estimating or monitoring the patients'
risk distribution. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425118
TI - Engaging conceptions of identity in a context of medical pluralism: explaining
treatment choices for everyday illness in Niger.
AB - This article uses ethnographic research to reflect upon how the treatment of
'everyday' illnesses in Niger engages concepts of social identity. Inspired by
Bourdieu's concept of social distinction, as well as Appadurai's edited volume on
the 'social lives' of 'things', I present an analysis of how medications are
understood by their users in terms of social and ideological meaning in one rural
Hausa village. Decisions about medication choice were framed by three main
themes: belonging to the 'modern' world, 'traditional' Hausa culture, and
religious identity. This article does not argue that these notions of identity
fully explain medication use, nor necessarily predict treatment choices. The
purpose of this paper is to reflect on the dynamic meanings given to treatment
decisions after they have been made, attributed to the medications themselves and
negotiated through their circulation in a context where multiple medical systems
are drawn from to manage illness. Producers and sellers of medication also engage
these meaning-centred concepts, which have theoretical and practical interest for
the social sciences and public health. A virtual abstract for this paper can be
viewed at: https://www.youtube.com/channel/UC_979cmCmR9rLrKuD7z0ycA.
PMID- 28425117
TI - Dream homes and dead ends in the city: a photo essay experiment.
AB - Research focused on the relationship between place and health demonstrates that
it is complex and shifting, as overlapping social, historical, institutional and
political and economic processes continually transform the landscapes in which
lived experiences are embedded. Understanding this relationship requires
knowledge of the situated meanings and local worlds that ethnographic methods are
well suited to investigate. However, even conventional ethnographic methods can
be inadequate to capture the embodied, lived experience of place - experiences in
which the sensory and inner processes of memory and imagination are often
privileged. Accessing these experiences and processes can require more
experimental methodological approaches. In this article, I present work from a
series of photo essays created between 2011 and 2016 by 15 young people who
inhabit the social, spatial and economic margins of Vancouver, Canada, and
discuss some of the challenges and opportunities presented by this methodology.
Created over 5 years, and broadly focused on how they understood, experienced and
navigated their 'place' in the city in the midst of poverty, addiction, violence
and physical and mental health crises, the photo essays young people produced are
embedded with personal biographies and trajectories, as well as shared
experiences of geography, precarity and possibility in Vancouver.
PMID- 28425119
TI - Mean-intercept anisotropy analysis of porous media. I. Analytic formulae for
anisotropic Boolean models.
AB - PURPOSE: Structure-property relations, which relate the shape of the
microstructure to physical properties such as transport or mechanical properties,
need sensitive measures of structure. What are suitable fabric tensors that
quantify the shape of anisotropic heterogeneous materials? The mean intercept
length is among the most commonly used characteristics of anisotropy in porous
media, for example, of trabecular bone in medical physics. METHODS: We analyze
the orientation-biased Boolean model, a versatile stochastic model that
represents microstructures as overlapping grains with an orientation bias towards
a preferred direction. This model is an extension of the isotropic Boolean model,
which has been shown to truthfully reproduce multi-functional properties of
isotropic porous media. We explain the close relationship between the concept of
intersections with test lines to the elaborate mathematical theory of queues, and
how explicit results from the latter can be directly applied to characterize
microstructures. RESULTS: In this series of two papers, we provide analytic
formulas for the anisotropic Boolean model and demonstrate often overlooked
conceptual shortcomings of this approach. Queuing theory is used to derive simple
and illustrative formulas for the mean intercept length. It separates into an
intensity-dependent and an orientation-dependent factor. The global average of
the mean intercept length can be expressed by local characteristics of a single
grain alone. CONCLUSIONS: We thus identify which shape information about the
random process the mean intercept length contains. The connection between global
and local quantities helps to interpret observations and provides insights into
the possibilities and limitations of the analysis. In the second paper of this
series, we discuss, based on the findings in this paper, short-comings of the
mean intercept analysis for (bone-)microstructure characterization. We will
suggest alternative and better defined sensitive anisotropy measures from
integral geometry.
PMID- 28425120
TI - Unravelling Swedish informal caregivers' Generalised Resistance Deficits.
AB - In salutogenic theory, individual/contextual, immaterial/material characteristics
enabling movements towards health are labelled Specific and Generalised
Resistance Resources, SRRs/GRRs, and characteristics counteracting such movements
Specific and Generalised Resistance Deficits, SRDs/GRDs. The aim of this paper
was to present SRDs and GRDs described by caregivers as stemming from themselves
and their care recipient. Guided by salutogenic theory, an explorative design was
used to collect data through interviews with 32 Swedish informal caregivers.
During the theory-driven analysis, SRDs were unravelled using within-case
approaches. To be able to unite them as GRDs across cases, a serviceable GRD
definition was developed from the existing theoretical GRR definition. In
findings, SRDs are visualised in citations and GRDs described in detail.
Caregivers' experiences of SRDs/GRDs are presented as themes: 'Experiencing
personal deficiencies', when stemming from themselves; and 'Struggling with an
uncooperative co-worker', when stemming from their care recipients. Findings
indicate that if these themes dominate a caregiver's view of life, she/he seems
to have reached the 'breaking point' when caregiving ends due to lack of usable
SRRs/GRRs. To prolong the time until this occurs, support, making otherwise
unusable SRRs/GRRs usable, is needed. When designing this type of 'salutogenic'
support, it seems essential to involve the target group (e.g. caregivers, care
recipients), to ascertain what their SRRs/GRRs and SRDs/GRDs may consist of. Such
knowledge regarding SRRs/SRDs could be used to design individualised support, and
regarding GRRs/GRDs to design generalised support at group level. This study
suggests how such new knowledge regarding resistance resources and deficits could
be acquired.
PMID- 28425122
TI - Mean-intercept anisotropy analysis of porous media. II. Conceptual shortcomings
of the MIL tensor definition and Minkowski tensors as an alternative.
AB - PURPOSE: Structure-property relations, which relate the shape of the
microstructure to physical properties such as transport or mechanical properties,
need sensitive measures of structure. What are suitable fabric tensors to
quantify the shape of anisotropic heterogeneous materials? The mean intercept
length is among the most commonly used characteristics of anisotropy in porous
media, e.g., of trabecular bone in medical physics. Yet, in this series of two
papers we demonstrate that it has conceptual shortcomings that limit the validity
of its results. METHODS: We test the validity of general assumptions regarding
the properties of the mean-intercept length tensor using analytical formulas for
the mean-intercept lengths in anisotropic Boolean models (derived in part I of
this series), augmented by numerical simulations. We discuss in detail the
functional form of the mean intercept length as a function of the test line
orientations. RESULTS: As the most prominent result, we find that, at least for
the example of overlapping grains modeling porous media, the polar plot of the
mean intercept length is in general not an ellipse and hence not represented by a
second-rank tensor. This is in stark contrast to the common understanding that
for a large collection of grains the mean intercept length figure averages to an
ellipse. The standard mean intercept length tensor defined by a least-square fit
of an ellipse is based on a model mismatch, which causes an intrinsic lack of
accuracy. CONCLUSIONS: Our analysis reveals several shortcomings of the mean
intercept length tensor analysis that pose conceptual problems and limitations on
the information content of this commonly used analysis method. We suggest the
Minkowski tensors from integral geometry as alternative sensitive measures of
anisotropy. The Minkowski tensors allow for a robust, comprehensive, and
systematic approach to quantify various aspects of structural anisotropy. We show
the Minkowski tensors to be more sensitive, in the sense, that they can quantify
the remnant anisotropy of structures not captured by the mean intercept length
analysis. If applied to porous tissue and microstructures, this improved
structure characterization can yield new insights into the relationships between
geometry and material properties.
PMID- 28425123
TI - A 5-Year Follow-Up of a Cohort of Italian Alcoholics: Hospital Admissions and
Overall Survival.
AB - BACKGROUND: Alcohol use disorders (AUDs), including alcohol dependence and
alcohol abuse defined according to specific DSM-IV and ICD-10 criteria, can be
potentially lethal, because they are associated with several medical and
psychiatric conditions. This study aimed to describe the causes of
hospitalization of a large cohort of subjects with alcohol dependence
(alcoholics) enrolled in Florence (Italy) over a 5-year follow-up period and to
evaluate the effect of hospitalization on overall survival. METHODS: One thousand
one hundred and thirty alcoholics, newly diagnosed from 1997 to 2001, were linked
to the Regional Mortality Registry for update of vital status as of December 31,
2006, and to the Hospital Discharge electronic archives of the Regional Health
System of Tuscany to verify hospital admissions (HAs) during the 5-year
postcohort enrollment follow-up. Kaplan-Meier survival and Cox regression
analyses were performed to evaluate any association of HA with overall survival.
RESULTS: A total of 3,916 new hospitalizations occurred during the 5-year follow
up. Most alcoholics (70.6%) reported at least 1 new hospitalization, with a first
hospitalization rate of 61.7 per 100 person-years in the first year of follow-up.
The mean number of hospitalizations per admitted subject was 4.87 (SD 7.4), and
mean length of hospital stay was 8.5 days (SD 11.3). The main causes of
hospitalization were mental disorders and diseases of the digestive system, as
well as accidents or violence. Among those alcoholics alive after 1 year of
follow-up, a significantly increased risk of dying in the following years could
be predicted by early hospitalization in the 12 months preceding (hazard ratio
[HR] 1.73; 95% confidence interval [CI] 1.15 to 2.60) or following (HR 3.59; 95%
CI 2.31 to 5.61) enrollment in the cohort. CONCLUSIONS: Our results confirm the
association of AUDs with several serious medical conditions. This fact may be
responsible for a high impact on health resource utilization and high social
costs. Early hospitalization significantly predicts vital status at 5 years.
PMID- 28425121
TI - Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational Effects of
Ethanol.
AB - Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor
(KOR) system contribute to various psychiatric disorders, including anxiety,
depression, and addiction. More recently, this endogenous opioid system has
received increased attention as a potential therapeutic target for treating
alcohol use disorders. In this review, we provide an overview and synthesis of
preclinical studies examining the influence of alcohol (ethanol [EtOH]) exposure
on DYN/KOR expression and function, as well as studies examining the effects of
DYN/KOR manipulation on EtOH's rewarding and aversive properties. We then
describe work that has characterized effects of KOR activation and blockade on
EtOH self-administration and EtOH dependence/withdrawal-related behaviors.
Finally, we address how the DYN/KOR system may contribute to stress-EtOH
interactions. Despite an apparent role for the DYN/KOR system in motivational
effects of EtOH, support comes from relatively few studies. Nevertheless, review
of this literature reveals several common themes: (i) rodent strains genetically
predisposed to consume more EtOH generally appear to have reduced DYN/KOR tone in
brain reward circuitry; (ii) acute and chronic EtOH exposure typically up
regulate the DYN/KOR system; (iii) KOR antagonists reduce behavioral indices of
negative affect associated with stress and chronic EtOH exposure/withdrawal; and
(iv) KOR antagonists are effective in reducing EtOH consumption, but are often
more efficacious under conditions that engender high levels of consumption, such
as dependence or stress exposure. These results support the contention that the
DYN/KOR system plays a significant role in contributing to dependence- and stress
induced elevation in EtOH consumption. Overall, more comprehensive analyses (on
both behavioral and mechanistic levels) are needed to provide additional insight
into how the DYN/KOR system is engaged and adapts to influence the motivation
effects of EtOH. This information will be critical for the development of new
pharmacological agents targeting KORs as promising novel therapeutics for alcohol
use disorders and comorbid affective disorders.
PMID- 28425124
TI - Is pyridoxine effective and safe for post-partum lactation inhibition? A
systematic review.
AB - WHAT IS KNOWN AND OBJECTIVE: It has been suggested that pyridoxine has an
antilactogenic effect. Studies of the efficacy of pyridoxine in suppressing
lactation have reported conflicting results. The aim of this review was to
evaluate the effectiveness and safety of high-dose pyridoxine in post-partum
lactation inhibition. METHODS: This systematic review included published trials
that compared the efficacy and/or safety of pyridoxine to placebo or to other
pharmacological agents for the inhibition of post-partum lactation. We searched
PubMed, Embase, ScienceDirect, CINAHL, AMED, the Cochrane library and the
clinical trials registry to identify relevant literature. No limit was imposed on
the year of publication of the studies, and the review included studies published
until 15 January 2016. Two reviewers independently extracted data and assessed
the risk of bias. RESULTS AND DISCUSSION: Seven studies were included, with a
total of 1155 women, of which 471 women received pyridoxine. Three studies were
randomized controlled trials, whereas the remaining four studies were non
randomized controlled trials. All of the included studies were relatively small
(n=18-482). The studies compared pyridoxine with placebo, bromocriptine and/or
stilboestrol. Pyridoxine was given orally, with a total daily dose of 450-600 mg
for 5-7 days. Two trials (n=349 participants) indicated that pyridoxine was
effective in inhibiting lactation in approximately 95% of the enrolled patients.
All other studies failed to demonstrate pyridoxine efficacy through either
clinical assessment or prolactin level measurements. Pyridoxine safety was
assessed by two trials in which no serious untoward side effects were reported.
Overall, the risk of bias for most of the studies was low to moderate. WHAT IS
NEW AND CONCLUSION: Current evidence supporting the effectiveness of high-dose
pyridoxine in the inhibition of post-partum lactation is inconsistent and
insufficient. Larger randomized trials are needed to confirm the efficacy of
pyridoxine in post-partum lactation inhibition.
PMID- 28425125
TI - N-Methyl-4-pyridinium Tetrazolate Zwitterion-Based Photochromic Materials.
AB - N,N'-Disubstituted bipyridinium (viologen) and N-monosubstituted bipyridinium
compounds are well known for their electron-transfer (ET) photochromic behavior.
Their modification has exclusively focused on the N-substituents to date. For the
first time, we have studied the photochromic behavior when one pyridyl ring of
the bipyridinium is substituted with a multifunctional azole group, and have
found that two new coordination compounds based on N-methyl-4-pyridinium
tetrazolate (mptz) zwitterion, [Zn(mptz)2 Br2 ] (1) and [Cd3 (mptz)2 Cl6 ]n ?4n
H2 O (2), exhibit typical ET photochromic behavior owing to photoinduced ET from
halogen anion to the mptz ligand. This work demonstrates a new simple, neutral
photoactive molecule with electron-accepting ability, which may act as a
photoactive component for materials with potential photoswitching and
photocatalysis applications.
PMID- 28425127
TI - Manipulation of glyoxalase pathway confers tolerance to multiple stresses in
rice.
AB - Crop plants face a multitude of diverse abiotic and biotic stresses in the
farmers' fields. Although there now exists a considerable knowledge of the
underlying mechanisms of response to individual stresses, the crosstalk between
response pathways to various abiotic and biotic stresses remains enigmatic. Here,
we investigated if the cytotoxic metabolite methylglyoxal (MG), excess of which
is generated as a common consequence of many abiotic and biotic stresses, may
serve as a key molecule linking responses to diverse stresses. For this, we
generated transgenic rice plants overexpressing the entire two-step glyoxalase
pathway for MG detoxification. Through assessment of various morphological,
physiological and agronomic parameters, we found that glyoxalase-overexpression
imparts tolerance towards abiotic stresses like salinity, drought and heat and
also provides resistance towards damage caused by the sheath blight fungus
(Rhizoctonia solani) toxin phenylacetic acid. We show that the mechanism of
observed tolerance of the glyoxalase-overexpressing plants towards these diverse
abiotic and biotic stresses involves improved MG detoxification and reduced
oxidative damage leading to better protection of chloroplast and mitochondrial
ultrastructure and maintained photosynthetic efficiency under stress conditions.
Together, our findings indicate that MG may serve as a key link between abiotic
and biotic stress response in plants.
PMID- 28425126
TI - Novel sequence variants in the LIPH and LPAR6 genes underlies autosomal recessive
woolly hair/hypotrichosis in consanguineous families.
AB - Autosomal-recessive woolly hair/hypotrichosis (ARWH/H) is a rare genetic disorder
of hair caused by variants in the LIPH and LPAR6 genes. The disease is
characterized by congenital tightly curled hair leading to sparse hair later in
life. In the present report genetic characterization of three consanguineous
families of Pakistani origin, displaying clinical features of ARWH/H, was
performed. Haplotype and DNA sequence analysis of the LIPH gene revealed a novel
homozygous nonsense variant (c.688C > T; p.Gln230*) in family A. In two other
families, B and C, sequence analysis of the LPAR6 gene revealed a novel
homozygous frameshift variant (c.68_69dupGCAT; p.Phe24Hisfs*29) and a previously
reported missense variant (c.188A > T; p.Asp63Val), respectively. Taken together,
our findings will expand the spectrum of variants reported in the LIPH and LPAR6
genes.
PMID- 28425128
TI - Understanding the effects of different social data on selecting priority
conservation areas.
AB - Conservation success is contingent on assessing social and environmental factors
so that cost-effective implementation of strategies and actions can be placed in
a broad social-ecological context. Until now, the focus has been on how to
include spatially explicit social data in conservation planning, whereas the
value of different kinds of social data has received limited attention. In a
regional systematic conservation planning case study in Australia, we examined
the spatial concurrence of a range of spatially explicit social values and land
use preferences collected using a public participation geographic information
system and biological data. We used Zonation to integrate the social data with
the biological data in a series of spatial-prioritization scenarios to determine
the effect of the different types of social data on spatial prioritization
compared with biological data alone. The type of social data (i.e., conservation
opportunities or constraints) significantly affected spatial prioritization
outcomes. The integration of social values and land-use preferences under
different scenarios was highly variable and generated spatial prioritizations 1.2
51% different from those based on biological data alone. The inclusion of
conservation-compatible values and preferences added relatively few new areas to
conservation priorities, whereas including noncompatible economic values and
development preferences as costs significantly changed conservation priority
areas (48.2% and 47.4%, respectively). Based on our results, a multifaceted
conservation prioritization approach that combines spatially explicit social data
with biological data can help conservation planners identify the type of social
data to collect for more effective and feasible conservation actions.
PMID- 28425129
TI - Role of sialyl 6-sulfo Lewis X in antitumor immunity against oral squamous cell
carcinoma.
AB - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) reportedly play a pivotal role
in antitumor immunity against oral squamous cell carcinoma (OSCC); however,
mechanisms governing TIL recruitment to OSCC tissues remain to be clarified. This
study was undertaken to assess a potential association between TILs and high
endothelial venule (HEV)-like vessels that express sialyl 6-sulfo Lewis X (LeX).
METHODS: OSCC tissue sections (n=41) were subjected to immunohistochemistry for
sialyl 6-sulfo LeX and CD34 to allow quantitation of HEV-like vessels. Triple
immunohistochemistry for sialyl 6-sulfo LeX and either CD3 and CD20 or CD4 and
CD8 was conducted to determine which lymphocyte subset is more closely associated
with HEV-like vessels. RESULTS: HEV-like vessels expressing sialyl 6-sulfo LeX
were detected in 27 of 41 (65.9%) OSCC cases, and these vessels were more
frequently found in early disease (T1/T2 stages) compared with advanced (T3/T4)
stages. The number of T cells attached to the inner surface of these HEV-like
vessels was significantly greater than that of B cells, while the number of CD4+
helper T cells and CD8+ cytotoxic T cells did not differ significantly.
Interestingly, sialyl 6-sulfo LeX was also expressed on the membrane of a
fraction of OSCC cells, and CD8+ cytotoxic T cells were almost exclusively found
attached to these carcinoma cells. CONCLUSIONS: Sialyl 6-sulfo LeX is displayed
not only on HEV-like vessels but also on OSCC cells and may potentially function
in antitumor immunity against OSCC.
PMID- 28425131
TI - Garlic Dermatitis on the Neck of an Infant Treated for Nasal Congestion.
AB - The health benefits of garlic (Allium sativum) as a naturopathic remedy have been
well documented, but topical application of garlic has been linked to allergic
and irritant contact dermatitis. We present a case of severe irritant contact
dermatitis due to application of a fresh garlic necklace to the neck of infant
for treatment of nasal congestion.
PMID- 28425130
TI - Histological grading based on poorly differentiated clusters is predictive of
tumour response and clinical outcome in rectal carcinoma treated with neoadjuvant
chemoradiotherapy.
AB - AIMS: The clinical outcome of patients with locally advanced rectal cancer who
undergo neoadjuvant chemoradiotherapy (CRT) is influenced by the tumour response
to treatment, which is reflected by tumour regression grade and post-treatment
(y) TNM stage. Little is known about the prognostic value of pretreatment
histopathological features of the tumour that may be useful to discriminate
potential non-responders and to design tailored therapeutic strategies. In this
study, we aimed to investigate the prognostic role of poorly differentiated
clusters (PDCs) of neoplastic cells in pretreatment biopsies of patients with
rectal cancer treated with neoadjuvant CRT. METHODS AND RESULTS: Grading based on
PDC counting was retrospectively applied to 204 pretreatment endoscopic biopsies
of rectal carcinomas from patients treated with neoadjuvant CRT and surgery.
Interobserver agreement in the assessment of PDC grade was good. High PDC grade
was significantly associated with high yT stage (P = 0.044), yM+ status (P =
0.0004), and unchanged TNM stage or TNM upstaging (P = 0.032). In addition, high
PDC grade was a significant and independent prognostic factor for cancer-specific
survival. CONCLUSIONS: PDC grade may be assessed in preoperative biopsies of
rectal cancer with good reproducibility. High PDC grade in a pretreatment tumour
is significantly associated with a poor response to therapy. Hence, we suggest
that PDC grading might be used as a significant predictive and prognostic factor
in patients with locally advanced rectal cancer who are treated with neoadjuvant
CRT, and to identify high-risk patients who need surgery and adjuvant
chemotherapy.
PMID- 28425132
TI - Early postoperative management after lung transplantation: Results of an
international survey.
AB - INTRODUCTION: Little data exist regarding optimal therapeutic strategies
postoperatively after lung transplant (LTx). Current practice patterns rely on
expert opinion and institutional experience resulting in nonuniform postoperative
care. To better define current practice patterns, an international survey of LTx
clinicians was conducted. METHODS: A 30-question survey was sent to transplant
clinicians via email to the International Society of Heart and Lung
Transplantation open forum mailing list and directly to the chief transplant
surgeon and pulmonologist of all LTx centers in the United States. RESULTS: Fifty
two clinicians representing 10 countries responded to the survey. Sedatives use
patterns included: opiates + propofol (57.2%), opiates + dexmedetomidine (18.4%),
opiates + intermittent benzodiazepines (14.3%), opiates + continuous
benzodiazepines (8.2%), and opiates alone (2%). About 40.4% reported no formal
sedation scale was followed and 13.5% of programs had no formal policy on
sedation and analgesia. A lung protective strategy was commonly employed, with
13.8%, 51.3%, and 35.9% of respondents using tidal volumes of <6 mL/kg ideal body
weight (IBW), 6 mL/kg IBW, and 8 mL/kg IBW, respectively. CONCLUSION: Practice
patterns in the early postoperative care of lung transplant recipients differ
considerably among centers. Many of the reported practices do not conform to
consensus guidelines on management of critically ill patients.
PMID- 28425133
TI - Fecal microbiota signatures of adult patients with different types of short bowel
syndrome.
AB - BACKGROUND AND AIM: Short bowel syndrome (SBS) is a common cause of intestinal
failure and can be divided into three types depending on intestinal anatomy. Gut
dysbiosis has been observed in pediatric SBS patients and is associated with
impaired outcome. Little is known about the changes in gut microbiota of adult
SBS patients. Therefore, we aim to characterize the fecal microbiota of adult
patients with different types of SBS. METHODS: Fifteen fecal samples from healthy
controls and adult patients with type II or type III SBS were collected (five in
each group). Fecal microbial compositions were determined by high-throughput
sequencing, and functional potential was predicted by Phylogenetic Investigation
of Communities by Reconstruction of Unobserved States. RESULTS: Bacterial alpha
diversity significantly decreased in SBS patients and positively correlated to
the remaining small bowel length. SBS II patients were enriched with
Proteobacteria but deficient in Firmicutes and Bacteroidetes. Whereas
Lactobacillus and Prevotella dominated the microbiomes of SBS III patients,
commensal bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae
declined in SBS patients. The parenteral nutrition duration of SBS patients was
positively related to the proportion of Enterobacteriaceae but negatively related
to Lactobacillus. Functional pathways of citrate cycle and branched-chain and
aromatic amino acid biosynthesis were abundant in SBS II patients, while
functional profiles of pyrimidine and purine metabolism were dominant in SBS III
patients. CONCLUSIONS: Short bowel syndrome patients have a marked intestinal
dysbiosis with type II SBS characterized by Proteobacteria and type III SBS
featured by Lactobacillus, resulting in altered functional profiles of fecal
microbiomes.
PMID- 28425134
TI - Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster
Hydroxylation Catalysis.
AB - Tyrosinase model systems pinpoint pathways to translating Nature's synthetic
abilities for useful synthetic catalysts. Mostly, they use N-donor ligands which
mimic the histidine residues coordinating the two copper centres. Copper
complexes with bis(pyrazolyl)methanes with pyridinyl or imidazolyl moieties are
already reported as excellent tyrosinase models. Substitution of the pyridinyl
donor results in the new ligand HC(3-tBuPz)2 (4-CO2 MePy) which stabilises a room
temperature stable MU-eta2 :eta2 -peroxide dicopper(II) species upon oxygenation.
It reveals highly efficient catalytic activity as it hydroxylates 8
hydroxyquinoline in high yields (TONs of up to 20) and much faster than all other
model systems (max. conversion within 7.5 min). Stoichiometric reactions with
para-substituted sodium phenolates show saturation kinetics which are nearly
linear for electron-rich substrates. The resulting Hammett correlation proves the
electrophilic aromatic substitution mechanism. Furthermore, density functional
theory (DFT) calculations elucidate the influence of the substituent at the
pyridinyl donor: the carboxymethyl group adjusts the basicity and nucleophilicity
without additional steric demand. This substitution opens up new pathways in
reactivity tuning.
PMID- 28425135
TI - Image editing for pathologists.
PMID- 28425136
TI - Molecularisation and metaphor.
AB - This article explores the molecularisation of medicine thesis by investigating
reports on genetics and molecular medicine in the New England Journal of
Medicine. While there has indeed been a large increase in the number of
references to molecules in the context of genetics over the last few decades
these are mostly embedded in a framework of explanatory metaphors, namely (gene)
expressivity, penetrance, regulation and pathways. As most of these metaphors are
drawn from the social world it would appear that the molecularisation thesis -
that social life is becoming dominated by the molecular - needs to be tempered by
the ways in which understanding of that molecular world is itself a reflection of
social life.
PMID- 28425137
TI - Three-Dimensional Printing: An Aid to Epidural Access for Neuromodulation.
AB - OBJECTIVE: The case report details to use of three-dimensional (3D) printing as
an aid to neuromodulation. METHODS: A patient is described in whom previous
attempts at spinal neuromodulation had failed due to lack of epidural or
intrathecal access, and the use of a 3D printed model allowed for improved
planning and ultimately, success. RESULTS: Successful spinal cord stimulation was
achieved with the plan developed by access to a 3D model of the patient's spine.
CONCLUSION: Neuromodulation techniques can provide the optimal analgesic
techniques for individual patients. At times these can fail due to lack of access
to the site for intervention, in this case epidural access. 3D printing may
provide additional information to improve the likelihood of access when anatomy
is distorted and standard approaches prove difficult.
PMID- 28425138
TI - Delivering dignified care: A realist synthesis of evidence that promotes
effective listening to and learning from older people's feedback in acute care
settings.
AB - AIMS AND OBJECTIVES: To explore effective mechanisms for listening to and
learning from feedback from older people in the context of acute care.
BACKGROUND: Maintaining the dignity of older people in acute care has become an
issue of international concern. In the United Kingdom, recommendations for care
improvement have led to the formation of an implementation group, the "Listening
and Learning Hospitals Pilot Project." This literature review forms phase 1 of
the project. DESIGN: Realist synthesis was used to explore and synthesise wide
ranging evidence. METHODS: Using 12 databases, literature was scoped to propose
four principles that underpin the context, mechanism and outcomes (CMO) of
effective relation-based interventions with older people and their care partners
in the acute care setting. A search was carried out in order to synthesise data
to refute or support each principle. A total of 137 studies and 11 sources of
grey literature were appraised and included. A final synthesis of evidence across
all principles identified key mechanisms for effective relation-based
interventions. RESULTS: Eight essential mechanisms support effective care
interventions. CONCLUSIONS: This review adds depth and breadth to current nursing
knowledge in this field through the process of realist synthesis. Acute care
organisations need to make a commitment to supporting relational care at
organisation and unit levels. Additionally, they need to value and support the
well-being of the nurses delivering it so that interventions to improve care for
older people can succeed. RELEVANCE TO CLINICAL PRACTICE: Essential mechanisms
synthesised from the review, together with other suggested interventions for
improving dignified care of older people in acute care by listening to them and
learning from their feedback, may contribute towards practice development in
acute care.
PMID- 28425139
TI - Dissecting Cellulitis of the Scalp with Excellent Response to Isotretinoin.
AB - An 18-year-old man presented for evaluation of a 1-year history of painful
nodules on the scalp with associated hair loss. Physical examination revealed
multiple confluent, fluctuant, boggy nodules on the scalp with overlying alopecic
patches. Based on these findings, a diagnosis of dissecting cellulitis of the
scalp was made and the patient was successfully treated with oral isotretinoin
therapy.
PMID- 28425140
TI - Response of parasitoid egg load to host dynamics and implications for egg load
evolution.
AB - A theoretical debate about whether parasitoids should be time or egg limited now
recognizes both as feasible, and interest has turned to determining the
circumstances under which each might arise in the field, and their implications
for parasitoid behaviour and evolution. Egg loads of parasitoids sampled from the
field are predicted to show a negative response to host availability, but
empirical support for this relationship is scarce. We measured how a parasitoid's
egg load responded to seasonal fluctuations in host population density and
recorded the predicted correlation. In early summer, parasitoids were at high
risk of time limitation due to low host availability, and in late summer, their
offspring were at greater risk of egg limitation due to high host availability.
Despite clear seasonal changes in selection pressures on egg load and lifespan,
the parasitoid showed no evidence of seasonal variation in its reproductive
strategy. We made minor modifications to a previously published model to explore
the effects of seasonal variation in host availability on optimal investments in
eggs and lifespan and obtained several new results. In particular, under
circumstances analogous to some of those observed in our field study, temporal
stochasticity in reproductive opportunities can cause investments in eggs to
increase, rather than decrease as previously predicted. Our model results helped
to explain the parasitoid's lack of a seasonally varying reproductive strategy.
Understanding the evolution of parasitoid egg load would benefit from a shift of
research emphasis from purely stochastic variation in parasitoid reproductive
opportunities to greater consideration of host dynamics.
PMID- 28425141
TI - Efficacy of Helicobacter pylori eradication therapies in Korea: A systematic
review and network meta-analysis.
AB - BACKGROUND: The efficacy of Helicobacter pylori eradication regimens may depend
on the country where the studies were performed because of the difference in
antibiotic resistance. We aimed to analyze the efficacy of H. pylori eradication
regimens in Korea where clarithromycin resistance rate is high. METHODS: We
searched for all relevant randomized controlled trials published until November
2016 that investigated the efficacy of H. pylori eradication therapies in Korea.
A network meta-analysis was performed to calculate the direct and indirect
estimates of efficacy among the eradication regimens. RESULTS: Forty-three
studies were identified through a systematic review, of which 34 studies,
published since 2005, were included in the meta-analysis. Among 21 included
regimens, quinolone-containing sequential therapy for 14 days (ST-Q-14) showed
the highest eradication rate (91.4% [95% confidence interval [CI], 86.9%-94.4%]
in the intention-to-treat [ITT] analysis). The eradication rate of the
conventional triple therapy for 7 days, standard sequential therapy for 10 days,
hybrid therapy for 10-14 days, and concomitant therapy for 10-14 days was 71.1%
(95% CI, 68.3%-73.7%), 76.2% (95% CI, 72.8%-79.3%), 79.4% (95% CI, 75.5%-82.8%),
and 78.3% (95% CI, 75.3%-80.9%), respectively, in the ITT analysis. In the
network meta-analysis, ST-Q-14 showed a better comparative efficacy than the
conventional triple therapy, standard sequential therapy, hybrid therapy, and
concomitant therapy. In addition, tolerability of ST-Q-14 was comparable to those
regimens. CONCLUSION: In Korea, ST-Q-14 showed the highest efficacy in terms of
eradication and a comparable tolerability, compared to the results reported for
the conventional triple therapy, standard sequential therapy, hybrid therapy, and
concomitant therapy.
PMID- 28425143
TI - What would Dr. James Parkinson think today? parcelling out the circuitry of
levodopa-induced dyskinesias.
PMID- 28425142
TI - Signaling complexes control the chemotaxis kinase by altering its apparent rate
constant of autophosphorylation.
AB - Autophosphorylating histidine kinase CheA is central to signaling in bacterial
chemotaxis. The kinase donates its phosphoryl group to two response regulators,
CheY that controls flagellar rotation and thus motility and CheB, crucial for
sensory adaptation. As measured by coupled CheY phosphorylation, incorporation
into signaling complexes activates the kinase ~1000-fold and places it under
control of chemoreceptors. By the same assay, receptors modulate kinase activity
~100-fold as a function of receptor ligand occupancy and adaptational
modification. These changes are the essence of chemotactic signaling. Yet, the
enzymatic properties affected by incorporation into signaling complexes, by
chemoreceptor ligand binding or by receptor adaptational modification are largely
undefined. To investigate, we performed steady-state kinetic analysis of
autophosphorylation using a liberated kinase phosphoryl-accepting domain,
characterizing kinase alone, in isolated core signaling complexes and in small
arrays of core complexes assembled in vitro with receptors contained in isolated
native membranes. Autophosphorylation in signaling complexes was measured as a
function of ligand occupancy and adaptational modification. Activation by
incorporation into signaling complexes and modulation in complexes by ligand
occupancy and adaptational modification occurred largely via changes in the
apparent catalytic rate constant (kcat ). Changes in the autophosphorylation kcat
accounted for most of the ~1000-fold kinase activation in signaling complexes
observed for coupled CheY phosphorylation, and the ~100-fold inhibition by ligand
occupancy or modulation by adaptational modification. Our results indicate no
more than a minor role in kinase control for simple sequestration of the
autophosphorylation substrate. Instead they indicate direct effects on the active
site.
PMID- 28425144
TI - Association between endoscopic findings related to colonic diverticula and bowel
habits: A multicenter study in Japan.
AB - BACKGROUND AND AIM: Few studies have shown the associations between colonic
diverticula and endoscopic findings such as location, inflammation, number of
diverticula, sigmoid colon rigidity, and bowel habits. METHODS: Japanese subjects
who underwent total colonoscopies at six centers in Japan from November 2015 to
October 2016 were analyzed. Bowel habits were evaluated using the
Gastrointestinal Symptom Rating Scale. Location and number of diverticula,
inflammation, and sigmoid colon rigidity were evaluated from endoscopy results.
RESULTS: A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose
mean age was 65.5 +/- 11.4 years were evaluated. In multivariate analysis,
presence of constipation was associated with a significantly lower likelihood of
left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20
0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula,
multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity
were not related to bowel habits. CONCLUSIONS: Among endoscopic findings related
to colonic diverticula and bowel habits, only left-sided colonic diverticula were
inversely associated with constipation, whereas inflammation findings, multiple
diverticula, and sigmoid colon rigidity were not related to bowel habits.
However, the association of inflammation findings with colonic diverticula and
bowel habits should be further studied. Investigation of changes in left-sided
colonic diverticula may lead to new treatments for constipation.
PMID- 28425145
TI - Prevalence of Gastroesophageal Reflux in Cats During Anesthesia and Effect of
Omeprazole on Gastric pH.
AB - BACKGROUND: Gastroesophageal reflux (GER) is poorly characterized in anesthetized
cats, but can cause aspiration pneumonia, esophagitis, and esophageal stricture
formation. OBJECTIVE: To determine whether pre-anesthetic orally administered
omeprazole increases gastric and esophageal pH and increases serum gastrin
concentrations in anesthetized cats, and to determine the prevalence of GER using
combined multichannel impedance and pH monitoring. ANIMALS: Twenty-seven healthy
cats undergoing elective dental procedures. METHODS: Prospective, double-masked,
placebo-controlled, randomized clinical trial. Cats were randomized to receive 2
PO doses of omeprazole (1.45-2.20 mg/kg) or an empty gelatin capsule placebo 18
24 hours and 4 hours before anesthetic induction. Blood for measurement of serum
gastrin concentration was collected during anesthetic induction. An esophageal
pH/impedance catheter was utilized to continuously measure esophageal pH and
detect GER throughout anesthesia. RESULTS: Mean gastric pH in the cats that
received omeprazole was 7.2 +/- 0.4 (range, 6.6-7.8) and was significantly higher
than the pH in cats that received the placebo 2.8 +/- 1.0 (range, 1.3-4.1; P <
.001). Omeprazole administration was not associated with a significant increase
in serum gastrin concentration (P = .616). Nine of 27 cats (33.3%) had >=1
episode of GER during anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Pre
anesthetic administration of 2 PO doses of omeprazole at a dosage of 1.45-2.20
mg/kg in cats was associated with a significant increase in gastric and
esophageal pH within 24 hours, but was not associated with a significant increase
in serum gastrin concentration. Prevalence of reflux events in cats during
anesthesia was similar to that of dogs during anesthesia.
PMID- 28425147
TI - Liver retransplantation: Recurrent primary sclerosing cholangitis may provide
better outcomes.
PMID- 28425146
TI - A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for
Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease.
AB - BACKGROUND: Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative
for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of
calves in a short period of time. The extent of commensal overgrowth and
agreement of BAL with DNS culture results in preweaned calves are unknown.
OBJECTIVES: To compare commensal overgrowth and bacterial culture results between
DNS and BAL samples. ANIMALS: A total of 183 preweaned calves (144 with bovine
respiratory disease and 39 healthy animals). METHODS: Cross-sectional study. Deep
nasopharyngeal swab and BAL samples were taken from each calf and cultured to
detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between
culture results of DNS and BAL samples were determined by kappa statistics and
logistic regression. RESULTS: Bronchoalveolar lavage samples were less often
polymicrobial, more frequently negative and yielded more pure cultures compared
to DNS, leading to a clinically interpretable culture result in 79.2% of the
cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in
healthy animals, but not different between DNS and BAL samples. Only Histophilus
somni was more likely to be isolated from BAL samples. In clinical cases, a
polymicrobial DNS culture result did not increase the probability of a
polymicrobial BAL result by >=30%, nor did it influence the probability of a
negative culture. A significant herd effect was noted for all observed
relationships. CONCLUSIONS AND CLINICAL RELEVANCE: Nonendoscopic BAL samples are
far less overgrown by bacteria compared to DNS samples under the conditions of
this study, facilitating clinical interpretation and resulting in a higher return
on investment in bacteriologic culturing.
PMID- 28425148
TI - Counting the publications that count.
PMID- 28425149
TI - Bayes' theorem and the rule of 100: a commentary on 'Validity of administrative
data for identification of obstructive sleep apnea'.
PMID- 28425151
TI - Split liver grafts can benefit both pediatric and adult liver transplant
recipients and programs.
PMID- 28425150
TI - Genetic basis for soma is present in undifferentiated volvocine green algae.
AB - Somatic cellular differentiation plays a critical role in the transition from
unicellular to multicellular life, but the evolution of its genetic basis remains
poorly understood. By definition, somatic cells do not reproduce to pass on genes
and so constitute an extreme form of altruistic behaviour. The volvocine green
algae provide an excellent model system to study the evolution of
multicellularity and somatic differentiation. In Volvox carteri, somatic cell
differentiation is controlled by the regA gene, which is part of a tandem
duplication of genes known as the reg cluster. Although previous work found the
reg cluster in divergent Volvox species, its origin and distribution in the
broader group of volvocine algae has not been known. Here, we show that the reg
cluster is present in many species without somatic cells and determine that the
genetic basis for soma arose before the phenotype at the origin of the family
Volvocaceae approximately 200 million years ago. We hypothesize that the
ancestral function was involved in regulating reproduction in response to stress
and that this function was later co-opted to produce soma. Determining that the
reg cluster was co-opted to control somatic cell development provides insight
into how cellular differentiation, and with it greater levels of complexity and
individuality, evolves.
PMID- 28425152
TI - NMR structures and molecular dynamics simulation of hylin-a1 peptide analogs
interacting with micelles.
AB - Antimicrobial peptides are recognized candidates with pharmaceutical potential
against epidemic emerging multi-drug resistant bacteria. In this study, we use
nuclear magnetic resonance spectroscopy and molecular dynamics simulations to
determine the unknown structure and evaluate the interaction with
dodecylphosphatidylcholine (DPC) and sodium dodecylsulphate (SDS) micelles with
three W6 -Hylin-a1 analogs antimicrobial peptides (HyAc, HyK, and HyD). The HyAc,
HyK, and HyD bound to DPC micelles are all formed by a unique alpha-helix
structure. Moreover, all peptides reach the DPC micelles' core, which thus
suggests that the N-terminal modifications do not influence the interaction with
zwiterionic surfaces. On the other hand, only HyAc and HyK peptides are able to
penetrate the SDS micelle core while HyD remains always at its surface. The
stability of the alpha-helical structure, after peptide-membrane interaction, can
also be important to the second step of peptide insertion into the membrane
hydrophobic core during permeabilization. Copyright (c) 2017 European Peptide
Society and John Wiley & Sons, Ltd.
PMID- 28425153
TI - Nursing students' preferences for clinical placements in the residential aged
care setting.
AB - AIMS AND OBJECTIVES: To examine nursing student placement preferences submitted
as online comments to a university's placement management system, to inform
strategies for positive residential aged care experiences. BACKGROUND: There are
predicted shortages of nurses to service an ageing population. Clinical
placements undertaken by undergraduate nursing students help shape their
attitudes and are a key determinant of career decision-making, yet there is
little research about why students prefer particular placement areas. DESIGN:
Analysis of qualitative data from a placement management system. METHODS: Of
6,610 comments received between 2007-2014, 607 related to aged care and were
coded according to preferences for being placed in a residential aged care
facility, with reasons for this preference thematically coded and quantified.
RESULTS: Four hundred and one comments (66.1%) related to students requesting not
to be allocated residential aged care for the upcoming placement, primarily due
to previous experience in the sector; 104 (17.1%) referred to aged care in a
neutral manner, focusing on conflict of interest; 102 (16.8%) related to a
request for an aged care placement. CONCLUSIONS: The student nurse comments
characterise students as being focused on maximising their learning, while
considering prior experience. In some cases, increased exposure to aged care is
considered to offer limited learning opportunities, which is concerning and
suggests that both the tertiary and aged care sectors have a joint responsibility
to pursue recognition of aged care nursing as a specialised, highly skilled role.
RELEVANCE TO CLINICAL PRACTICE: Nursing programme providers should ensure
curriculum content and exposure to aged care placement clearly identify the
complexities of care and provide genuine opportunities for knowledge acquisition
and skill development based on multifaceted resident care needs. This will
support both those interested in a future aged care career and those undecided.
PMID- 28425154
TI - Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study.
AB - AIM: Gut microbial dysbiosis is implicated in the pathogenesis of non-alcoholic
steatohepatitis (NASH). We investigated downstream effects of gut microbiota
modulation on markers of hepatic inflammation, steatosis, and hepatic and
peripheral insulin sensitivity in patients with NASH using rifaximin therapy.
METHODS: Patients with biopsy-proven NASH and elevated aminotransferase values
were included in this open-label pilot study, all receiving 6 weeks rifaximin 400
mg twice daily, followed by a 6-week observation period. The primary endpoint was
change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary
endpoints were change in hepatic lipid content and insulin sensitivity measured
with a hyperinsulinemic-euglycemic clamp. RESULTS: Fifteen patients (13 men and 2
women) with a median (range) age of 46 (32-63) years were included. Seven had
diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of
therapy, no differences were seen in ALT (55 [33-191] vs. 63 [41-218] IU/L, P =
0.41), peripheral glucose uptake (28.9 [19.4-48.3] to 25.5 [17.7-47.9]
MUmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3-51.7]% vs. 30.0
[10.8-50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2-46.2]% vs. 24.8 [1.7
59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from
baseline, serum ALT increased to 83 (30-217) IU/L, P = 0.02. There was a
significant increase in the homeostasis model assessment-estimated insulin
resistance index (P = 0.05). The urinary metabolic profile indicated a
significant reduction in urinary hippurate with treatment, which reverted to
baseline after cessation of rifaximin, although there was no consistent
difference in relative abundance of fecal microbiota with treatment. CONCLUSION:
These data do not indicate a beneficial effect of rifaximin in patients with
NASH.
PMID- 28425155
TI - Effect of platinum on sintering morphology of porous YSZ ceramics.
AB - Platinum/yttria-stabilized zirconia (Pt/YSZ) porous ceramics were prepared by
sintering of the Pt/PMMA/YSZ stripe-like membrane with a porogen of spherical
polymethyl methacrylate (PMMA) and a precursor of platinum (Pt) of chloroplatinic
acid. The microstructure of raw and processed material and Pt/ZrO2 calcination
process at different sintering temperatures were investigated. The results showed
that the spherically porous structure of Pt/YSZ was observed at a sintering
temperature below 400 degrees C due to the thermal decomposition of PMMA.
However, the pores were shrunk about 35% in diameter when YSZ compacts were
sintered at the temperature of 1,450 degrees C. In addition, the spherical pores
can be retained in the compacts when the content of Pt <5% and then gradually
merged into changing when the content of Pt increased to 50%. The relative
density was increased from 42% to 90% and the open porosity was decreased from
60% to 10% when Pt was added with content from 5% to 80%. The change of
microstructure for Pt/YSZ is due to the migration of Pt and YSZ in the
composites. The preferential migration and coalescence proceeded for Pt in Pt/YSZ
is about 500 degrees C and YSZ clusters can keep stable until up to 900 degrees
C. However, the growth of YSZ particle in the sintering process was hindered by
the scattering of Pt phase.
PMID- 28425156
TI - Universal vs selective ultrasonography to screen for large-for-gestational-age
infants and associated morbidity.
AB - OBJECTIVES: To compare the diagnostic effectiveness of selective vs universal
ultrasonography as a screening test for large-for-gestational-age (LGA) infants,
and to determine whether previously described ultrasound markers of excessive
fetal growth could identify suspected LGA fetuses that are at increased risk of
adverse neonatal outcome. METHODS: Data from the Pregnancy Outcome Prediction
study, a prospective cohort study of nulliparous women with a viable singleton
pregnancy at the time of the dating ultrasound scan, were analyzed. Women were
selected for clinically indicated ultrasound assessment in the third trimester as
per routine clinical care, and the results of these scans were reported
('selective ultrasonography'). In addition, all participants underwent research
ultrasound scans, including estimated fetal weight (EFW) assessment, at around 36
weeks' gestation, in which both the women and their clinicians were blinded to
the results ('universal ultrasonography'). Participants who attended the 36-week
research scan and had a live birth at the Rosie Hospital were included in the
study. Screen positive for LGA was defined as EFW > 90th percentile at >= 34
weeks. RESULTS: The current analysis included 3866 eligible women, of whom 1354
(35%) had a clinically indicated ultrasound scan at or after 34 weeks' gestation.
A total of 177 (4.6%) infants had a birth weight > 90th percentile. The
sensitivity for detection of LGA infants was 27% for selective ultrasonography
and 38% for universal ultrasonography. The specificity of both approaches was
high (99% and 97%, respectively). Using universal ultrasonography, neonatal
outcome differed (P for interaction) by abdominal circumference growth velocity
(ACGV) for both any neonatal morbidity (P = 0.08) and severe adverse neonatal
outcome (P = 0.03). LGA fetuses with increased ACGV had a relative risk of any
neonatal morbidity of 2.0 (95% CI, 1.1-3.6; P = 0.04) and of severe adverse
neonatal outcome of 6.5 (95% CI, 2.0-21.1; P = 0.01), whereas LGA fetuses with
normal ACGV were not at increased risk. CONCLUSIONS: Third-trimester screening of
nulliparous women by universal ultrasound fetal biometry increases the detection
rate of LGA infants and, combined with ACGV, identifies those at increased risk
of adverse neonatal outcome. Copyright (c) 2017 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 28425157
TI - Geographic variation in mimetic precision among different species of coral snake
mimics.
AB - Batesian mimicry is widespread, but whether and why different species of mimics
vary geographically in resemblance to their model is unclear. We characterized
geographic variation in mimetic precision among four Batesian mimics of coral
snakes. Each mimic occurs where its model is abundant (i.e. in 'deep sympatry'),
rare (i.e. at the sympatry/allopatry boundary or 'edge sympatry') and absent
(i.e. in allopatry). Geographic variation in mimetic precision was qualitatively
different among these mimics. In one mimic, the most precise individuals occurred
in edge sympatry; in another, they occurred in deep sympatry; in the third, they
occurred in allopatry; and in the fourth, precise mimics were not concentrated
anywhere throughout their range. Mimicry was less precise in allopatry than in
sympatry in only two mimics. We present several nonmutually exclusive hypotheses
for these patterns. Generally, examining geographic variation in mimetic
precision - within and among different mimics - offers novel insights into the
causes and consequences of mimicry.
PMID- 28425158
TI - Sexual coloration and sperm performance in the Australian painted dragon lizard,
Ctenophorus pictus.
AB - Theory predicts trade-offs between pre- and post-copulatory sexually selected
traits. This relationship may be mediated by the degree to which males are able
to monopolize access to females, as this will place an upper limit on the
strength of post-copulatory selection. Furthermore, traits that aid in mate
monopolization may be costly to maintain and may limit investment in post
copulatory traits, such as sperm performance. Australian painted dragons are
polymorphic for the presence or absence of a yellow gular patch ('bibs'), which
may aid them to monopolize access to females. Previous work has shown that there
are physiological costs of carrying this bib (greater loss of body condition in
the wild). Here, we show that male painted dragons use this bright yellow bib as
both an inter- and intrasexual signal, and we assess whether this signal is
traded off against sperm performance within the same individuals. We found no
relationship between aspects of bib colour and sperm swimming velocity or
percentage of motile sperm and suggest that the bib polymorphism may be
maintained by complex interactions between physiological or life-history traits
including other sperm or ejaculate traits and environmental influences.
PMID- 28425159
TI - N-terminal diproline and charge group effects on the stabilization of helical
conformation in alanine-based short peptides: CD studies with water and methanol
as solvent.
AB - Protein folding problem remains a formidable challenge as main chain, side chain
and solvent interactions remain entangled and have been difficult to resolve.
Alanine-based short peptides are promising models to dissect protein folding
initiation and propagation structurally as well as energetically. The effect of N
terminal diproline and charged side chains is assessed on the stabilization of
helical conformation in alanine-based short peptides using circular dichroism
(CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys
Ala-NH2 ) is designed to assess the effect of N-terminal homochiral diproline and
lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala
Lys-Lys-Ala-NH2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH2 ) with N
terminal homochiral and heterochiral diproline, respectively, are designed to
assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the
stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water
manifest different amplitudes of the observed polyproline II (PPII) signals,
which indicate different conformational distributions of the polypeptide
structure. The strong effect of solvent substitution from water to methanol is
observed for the peptides, and CD spectra in methanol evidence A2 and A3 as
helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an
isodichroic point reflecting coexistence of two conformations, PPII and beta
strand conformation, which is consistent with the previous studies. The results
illuminate the effect of N-terminal diproline and charged side chains in
dictating the preferences for extended-beta, semi-extended PPII and helical
conformation in alanine-based short peptides. The results of the present study
will enhance our understanding on stabilization of helical conformation in short
peptides and hence aid in the design of novel peptides with helical structures.
Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
PMID- 28425160
TI - Causes of nephrotic syndrome and nephrotic-range proteinuria are different in
adult Chinese patients: A single centre study over 33 years.
AB - AIM: The reported causes of nephrotic syndrome (NS) varies between different
countries. Less is known about the causes of nephrotic-range proteinuria (NPU).
We aimed to evaluate the underlying causes of NS and NPU. METHODS: This was a
single-centre, retrospective study of adult patients who underwent renal biopsy
between 1983 and 2015 in a tertiary referral hospital in Hong Kong. We determined
the distribution of histopathological diagnoses with regard to the age subgroups
and time periods. RESULTS: Among 7456 patients who underwent renal biopsy, 982
and 838 patients had NS and NPU, respectively. The most common diagnosis in NS
was minimal change disease (MCD) (33.3%), followed by membranous nephropathy (MN)
(23.6%) and lupus nephritis (LN) (12.8%); whereas the most common diagnosis in
NPU was LN (27.4%), followed by immunoglobulin A nephropathy (IgAN) (21.4%) and
diabetic nephropathy (DN) (9.3%). In the NS group, MCD was the most common
diagnosis in young adults while MN was the leading cause in the elderly. On the
other hand, LN was the most common pathology in the NPU group until the age of
60. Over the past three decades, there was a trend of decrease in the proportion
of IgAN in both NS and NPU group, while a combined pathology of hypertensive
nephrosclerosis and diabetic nephropathy (HTNS and DN) increased significantly.
CONCLUSIONS: The causes of NS and NPU in Chinese adults were different and may
represent two distinct pathological identities. The spectrum of renal
histopathology among these two groups changed significantly over time.
PMID- 28425161
TI - Atorvastatin treatment modulates p16 promoter methylation to regulate p16
expression.
AB - Intimal hyperplasia, the key event of arterial restenosis, is a result of cell
proliferation and cell migration. Atorvastatin exerts an inhibitory effect on
cell proliferation and migration, but the mechanism remains largely unknown. p16,
as a well-known tumor suppressor, was also reported to suppress cell growth and
migration, but with an unclear mechanism. In this study, we demonstrated that
atorvastatin represses cell proliferation and migration in vascular smooth muscle
cells (VSMCs) and that this process is mediated by p16. Furthermore, we found
that DNA methylation in the p16 promoter was reduced and p16 expression was
restored in VSMCs treated with 5-aza-2'-deoxycytidine or atorvastatin. However,
the effect was absent when DNA methyltransferase 1 (DNMT1) was knocked down with
RNA interference. These observations demonstrated that atorvastatin regulates p16
expression via DNMT1-induced DNA methylation in the p16 promoter. In addition, we
found that the mitogen-activated protein kinase (MAPK) pathway was involved in
the regulation of p16 by DNMT1, and MAPK inhibitors partially released the
effects of atorvastatin on p16 and DNMT1. Finally, we illustrated that
atorvastatin inhibits neointima formation and modulates p16 expression in balloon
catheter-injured rat carotid artery. Taken together, we demonstrated that
atorvastatin inhibits neointima formation through inducing p16 expression by
affecting DNA methylation in the p16 promoter region.
PMID- 28425162
TI - A small 'lick' will sink a great ship: fulminant septicaemia after dog saliva
wound treatment in an asplenic patient.
AB - Capnocytophaga canimorsus is a bacterium transmitted through the saliva of dogs.
An infection can cause severe sepsis with acral necrosis and is potentially
fatal. Here, we report the case of a 41-year-old man who was infected through a
wound that was licked by his dog. He went into septic shock with disseminated
intravascular coagulation and subsequently lost both lower legs, his nose and all
the fingers on both hands.
PMID- 28425163
TI - Abstracts of the UROFAIR 2017, Individualised Urological Treatment, 20-22 April
2017, Singapore.
PMID- 28425164
TI - The fallacy of resting echocardiographic parameters of cardiac function in heart
failure with preserved ejection fraction: add global longitudinal strain to the
list.
PMID- 28425165
TI - Melanogenesis-Inhibitory and Cytotoxic Activities of Limonoids, Alkaloids, and
Phenolic Compounds from Phellodendron amurense Bark.
AB - Four limonoids, 1 - 4, five alkaloids, 5 - 9, and four phenolic compounds, 10 -
13, were isolated from a MeOH extract of the bark of Phellodendron amurense
(Rutaceae). Among these, compound 13 was new, and its structure was established
as rel-(1R,2R,3R)-5-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-1
(methoxycarbonylmethyl)indane-2-carboxylic acid methyl ester (gamma-di(methyl
ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1 -
13 against the melanogenesis in the B16 melanoma cells induced with alpha
melanocyte-stimulating hormone (alpha-MSH), four compounds, limonin (1),
noroxyhydrastinine (6), haplopine (7), and 4-methoxy-1-methylquinolin-2(1H)-one
(8), exhibited potent melanogenesis-inhibitory activities with almost no toxicity
to the cells. Western blot analysis revealed that compound 6 inhibited
melanogenesis, at least in part, by inhibiting the expression of protein levels
of tyrosinase, TRP-1, and TRP-2 in alpha-MSH-stimulated B16 melanoma cells. In
addition, when compounds 1 - 13 were evaluated for their cytotoxic activities
against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK-BR-3)
cancer cell lines, five compounds, berberine (5), 8, canthin-6-one (9), alpha-di
(methyl ferulate) (12), and 13, exhibited cytotoxicities against one or more
cancer cell lines with IC50 values in the range of 2.6 - 90.0 MUm. In particular,
compound 5 exhibited strong cytotoxicity against AZ521 (IC50 2.6 MUm) which was
superior to that of the reference cisplatin (IC50 9.5 MUm).
PMID- 28425166
TI - Uranyl Photocleavage of Phosphopeptides Yields Truncated C-Terminally Amidated
Peptide Products.
AB - The uranyl ion (UO22+ ) binds phosphopeptides with high affinity, and when
irradiated with UV-light, it can cleave the peptide backbone. In this study, high
accuracy tandem mass spectrometry and enzymatic assays were used to characterise
the photocleavage products resulting from the uranyl photocleavage reaction of a
tetraphosphorylated beta-casein model peptide. We show that the primary
photocleavage products of the uranyl-catalysed reaction are C-terminally
amidated. This could be of great interest to the pharmaceutical industry, as
efficient peptide amidation reactions are one of the top challenges in green
pharmaceutical chemistry.
PMID- 28425167
TI - Continuous subcutaneous insulin infusion: Special needs for children.
AB - Continuous subcutaneous insulin infusion (CSII) is a very common therapy for
children with type 1 diabetes. Due to physiological differences they have other
requirements for their insulin pump than adults. The main difference is the need
for very low basal rates. Even though most available insulin pumps reach a high
accuracy at usual basal rates, accuracy decreases for lower rates. In addition,
the lowest delivered amount at 1 time is limiting the fine tuning of the basal
rate as well as the option for temporary basal rates. Alarms in case of
occlusions depend on accumulation of a certain amount of insulin in the catheter,
and therefore the time until such an alarm is triggered is much longer with lower
basal rates. Accordingly, the risk for hyperglycemia developing into diabetic
ketoacidosis increases. The availability of bolus advisors facilitates the
calculation of meal and correction boluses for children and their parents.
However, there are some differences between the calculators, and the settings
that the calculation is based on are very important. Better connectivity, for
example with a system for continuous glucose monitoring, might help to further
increase safety in the use of CSII in children. When selecting an insulin pump
for a child, the features and characteristics of available pumps should be
properly compared to ensure an effective and safe therapy.
PMID- 28425168
TI - Right ventricular failure after left ventricular assist device implant: 'towards
finding common ground'.
PMID- 28425169
TI - A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester
Hydrogenation.
AB - A new hydrogenation catalyst based on a manganese complex of a chiral P,N,N
ligand has been found to be especially active for the hydrogenation of esters
down to 0.1 mol % catalyst loading, and gives up to 97 % ee in the hydrogenation
of pro-chiral deactivated ketones at 30-50 degrees C.
PMID- 28425170
TI - Brief Report: Rheumatoid Arthritis as the Underlying Cause of Death in Thirty-One
Countries, 1987-2011: Trend Analysis of World Health Organization Mortality
Database.
AB - OBJECTIVE: To examine trends in rheumatoid arthritis (RA) as an underlying cause
of death (UCD) in 31 countries across the world from 1987 to 2011. METHODS: Data
on mortality and population were collected from the World Health Organization
mortality database and from the United Nations Population Prospects database. Age
standardized mortality rates (ASMRs) were calculated by means of direct
standardization. We applied joinpoint regression analysis to identify trends.
Between-country disparities were examined using between-country variance and the
Gini coefficient. Due to low numbers of deaths, we smoothed the ASMRs using a 3
year moving average. Changes in the number of RA deaths between 1987 and 2011
were decomposed using 2 counterfactual scenarios. RESULTS: The absolute number of
deaths with RA registered as the UCD decreased from 9,281 (0.12% of all-cause
deaths) in 1987 to 8,428 (0.09% of all-cause deaths) in 2011. The mean ASMR
decreased from 7.1 million person-years in 1987-1989 to 3.7 million person-years
in 2009-2011 (48.2% reduction). A reduction of >=25% in the ASMR occurred in 21
countries, while a corresponding increase was observed in 3 countries. There was
a persistent reduction in RA mortality, and on average, the ASMR declined by 3.0%
per year. The absolute and relative between-country disparities decreased during
the study period. CONCLUSION: The rates of mortality attributable to RA have
declined globally. However, we observed substantial between-country disparities
in RA mortality, although these disparities decreased over time. Population aging
combined with a decline in RA mortality may lead to an increase in the economic
burden of disease that should be taken into consideration in policy-making.
PMID- 28425171
TI - How is continuity of care experienced by people living with chronic kidney
disease?
AB - AIMS AND OBJECTIVES: To explore patients' perceptions of continuity of care
within a hospital-based specialist service. BACKGROUND: Patient journeys through
health care are becoming increasingly complex. For patients with chronic
conditions, the longevity of their illness and common multiple co-morbidities
make this complexity more pronounced. Continuity of care is most challenging to
provide for these patients. A multifaceted model of continuity is widely
accepted, but despite this, much literature focuses exclusively on relational
aspects. In addition, the majority of the literature has focused on primary and
family care settings whilst continuity within specialist and hospital care has
not been widely researched. DESIGN: A qualitative descriptive design was used.
METHODS: Thirteen semi-structured interviews with patients accessing services as
at a Renal and Transplant Unit at a UK hospital were conducted in 2014. Data were
analysed thematically to identify commonality as well as diversity amongst
participants. RESULTS: Five themes of time, being known, knowledge, knowing the
system and responsibility were identified within patient experiences of
continuity. The multidisciplinary team was more important in relational
continuity than literature has previously suggested. Patients' expectations in
relation to continuity were notably different in their interactions with hospital
based services in comparison with community and family-based care. CONCLUSIONS:
Patients accessing specialist care services may perceive continuity differently
to those receiving care in the community. Generic guidance concerned with patient
experience outcomes may be difficult to implement in practice. RELEVANCE TO
CLINICAL PRACTICE: Nurses and the wider healthcare team play a fundamental role
within the provision of continuity, even in predominantly medically led
specialist services. The differences between primary and secondary care in terms
of patient expectation and experience should be recognised to ensure effective
models of care are implemented which both meet patient expectations and improve
their experience of care.
PMID- 28425172
TI - The homeostatic and circadian sleep recovery responses after total sleep
deprivation in mice.
AB - Many studies on sleep deprivation effects lack data regarding the recovery
period. We investigated the 2-day homeostatic and circadian sleep recovery
response to 24 h of total sleep deprivation (TSD) induced by brief rotation of an
activity wheel. Eight mice were implanted with telemetry transmitters (DSI F40
EET) that recorded simultaneously their electroencephalography (EEG), locomotor
activity and temperature during 24 h of baseline (BSL), TSD and 2 days of
recovery (D1 and D2). In a second experiment, two groups of five non-implanted
mice underwent TSD or ad libitum sleep, after which they were killed, adrenal
glands were weighed and blood was collected for analysis of corticosterone
concentration. During TSD mice were awake at least 97% of the time, with a
consecutive sleep rebound during D1 that persisted during D2. This was
characterized by increases of non-rapid eye movement (NREM) sleep (44.2 +/- 6.9%
for D1 and 43.0 +/- 7.7% for D2 versus 33.8 +/- 9.2% for BSL) and the relative
delta band power (179.2 +/- 34.4% for D1 and 81.9 +/- 11.2% for D2). Greater NREM
and REM sleep amounts were observed during the 'light' periods. Temperature and
locomotor activity characteristics were unchanged during D1 and D2 versus BSL. In
non-implanted mice, corticosterone levels as well as adrenal gland and overall
body weights did not differ between TSD and ad libitum sleep groups. In
conclusion, 24 h of TSD in an activity wheel without stress responses influence
homeostatic sleep regulation with no effect on the circadian regulation over at
least 2 days of recovery in mice.
PMID- 28425173
TI - Twenty-Year Outcome and Association Between Early Treatment and Mortality and
Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results
From the Norfolk Arthritis Register.
AB - OBJECTIVE: To describe the outcome in patients with rheumatoid arthritis (RA)
over 20 years from symptom onset, and to assess the association between early
treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and
disability during follow-up. METHODS: Patients recruited to the Norfolk Arthritis
Register (NOAR) between 1990 and 1994 who met the 2010 American College of
Rheumatology/European League Against Rheumatism RA criteria at baseline were
included in this analysis. Demographic and clinical variables were collected at
baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint
count [SJC]/tender joint count [TJC]), disability (Health Assessment
Questionnaire disability index [HAQ DI]), and mortality over 20 years were
determined. Associations between treatment group (early treatment [ET], treatment
<=6 months after symptom onset; late treatment [LT], treatment >6 months after
symptom onset; never treatment [NT], no treatment) and mortality and disability
were assessed using weighted pooled logistic regression and weighted multilevel
mixed-effects linear regression, respectively. Inverse weights were used to
account for confounding by indication and censoring. RESULTS: This study included
602 patients with RA (median age 56 years [interquartile range 44-68 years];
65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3
swollen joints and 3-6 tender joints). The median HAQ DI score increased after
year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk
of mortality was reduced in the ET and LT groups compared with that in the NT
group. The ET group and the NT group had comparable HAQ DI scores during the
follow-up period (beta = 0.03, 95% confidence interval [95% CI] -0.06, 0.12),
while the HAQ DI score was increased in the LT group (for LT versus NT, beta =
0.10 [95% CI 0.02, 0.17]). CONCLUSION: The results of this study indicate the
importance of early treatment with regard to the long-term outcomes in patients
with RA.
PMID- 28425174
TI - Costs and benefits of sublethal Drosophila C virus infection.
AB - Viruses are major evolutionary drivers of insect immune systems. Much of our
knowledge of insect immune responses derives from experimental infections using
the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal
pathogen doses through septic injury, frequently overwhelming host physiology.
While this approach has revealed several immune mechanisms, it is less
informative about the fitness costs hosts may experience during infection in the
wild. Using both systemic and oral infection routes, we find that even apparently
benign, sublethal infections with the horizontally transmitted Drosophila C virus
(DCV) can cause significant physiological and behavioural morbidity that is
relevant for host fitness. We describe DCV-induced effects on fly reproductive
output, digestive health and locomotor activity, and we find that viral morbidity
varies according to the concentration of pathogen inoculum, host genetic
background and sex. Notably, sublethal DCV infection resulted in a significant
increase in fly reproduction, but this effect depended on host genotype. We
discuss the relevance of sublethal morbidity for Drosophila ecology and
evolution, and more broadly, we remark on the implications of deleterious and
beneficial infections for the evolution of insect immunity.
PMID- 28425175
TI - Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which
disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo.
AB - Snake venom metalloproteases (SVMPs) are members of the a disintegrin and
metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs
are known to elicit snake venom-induced haemorrhage; however, the target proteins
and cleavage sites are not known. In this work, we identified a target protein of
vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to
induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin
and gamma-catenin from the cell-cell junction to the cytosol, without inducing
proteolysis of VE-cadherin. The Wnt receptors low-density lipoprotein receptor
related proteins 5 and 6 (LRP5/6) are known to promote catenin relocation, and
are rendered constitutively active in Wnt signalling by truncation. Thus, we
examined whether VAP1 cleaves LRP5/6 to induce catenin relocation. Indeed, we
found that VAP1 cleaved the extracellular region of LRP6 and LRP5. This cleavage
removes four inhibitory beta-propeller structures, resulting in activation of
LRP5/6. Recombinant human ADAM8 and ADAM12 also cleaved LRP6 at the same site. An
antibody against a peptide including the LRP6-cleavage site inhibited VAP1
induced VE-cadherin relocation and disruption of cell-cell adhesions in cultured
cells, and blocked haemorrhage in mice in vivo. Intriguingly, animals resistant
to the effects of haemorrhagic snake venom express variants of LRP5/6 that lack
the VAP1-cleavage site, or low-density lipoprotein receptor domain class A
domains involved in formation of the constitutively active form. The results
validate LRP5/6 as physiological targets of ADAMs. Furthermore, they indicate
that SVMP-induced cleavage of LRP5/6 causes disruption of cell-cell adhesion and
haemorrhage, potentially opening new avenues for the treatment of snake bites.
PMID- 28425176
TI - Polyhydroxyalkanoate-associated phasins as phylogenetically heterogeneous,
multipurpose proteins.
AB - Polyhydroxyalkanoates (PHAs) are natural polyesters of increasing
biotechnological importance that are synthesized by many prokaryotic organisms as
carbon and energy storage compounds in limiting growth conditions. PHAs
accumulate intracellularly in form of inclusion bodies that are covered with a
proteinaceous surface layer (granule-associated proteins or GAPs) conforming a
network-like surface of structural, metabolic and regulatory polypeptides, and
configuring the PHA granules as complex and well-organized subcellular structures
that have been designated as 'carbonosomes'. GAPs include several enzymes related
to PHA metabolism (synthases, depolymerases and hydroxylases) together with the
so-called phasins, an heterogeneous group of small-size proteins that cover most
of the PHA granule and that are devoid of catalytic functions but nevertheless
play an essential role in granule structure and PHA metabolism. Structurally,
phasins are amphiphilic proteins that shield the hydrophobic polymer from the
cytoplasm. Here, we summarize the characteristics of the different phasins
identified so far from PHA producer organisms and highlight the diverse
opportunities that they offer in the Biotechnology field.
PMID- 28425177
TI - Design and Synthesis of C3-Substituted beta-Carboline-Based Histone Deacetylase
Inhibitors with Potent Antitumor Activities.
AB - A series of hydroxamic acid histone deacetylase (HDAC) inhibitors in which the
beta-carboline motif has been incorporated were designed and synthesized. The
effect of substitution at the C3 amide on HDAC inhibition and antiproliferative
activities was investigated. Most of these compounds were found to display
significant HDAC inhibitory effects and good antiproliferative activity, with
IC50 values in the low-micromolar range. In particular, the HDAC inhibition IC50
value of N-(2-(dimethylamino)ethyl)-N-(4-(hydroxylcarbamoyl)benzyl)-1-(4
methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (9 h) is five-fold lower than
that of suberoylanilide hydroxamic acid (SAHA, vorinostat). Furthermore, 9 h was
found to increase the acetylation of histone H3 and alpha-tubulin, and to induce
DNA damage as evidenced by hypochromism and enhanced phosphorylation of histone
H2AX. Compound 9 h inhibits Stat3, Akt, and ERK signaling, important cell-growth
promoting pathways that are aberrantly activated in most cancers. Finally, 9 h
showed reasonable solubility and permeability in Caco-2 cells. Our findings
suggest that these novel beta-carboline-based HDAC inhibitors may hold great
promise as therapeutic agents for the treatment of human cancers.
PMID- 28425178
TI - Sleep quality, clinical and psychological manifestations in women with systemic
lupus erythematosus.
AB - AIM: Sleep problems are a common complaint in systemic lupus erythematosus (SLE)
patients. We analyzed sleep quality with subjective and objective measures in a
sample with SLE and its possible relationships with the main manifestations of
the disease. METHODS: Twenty-one women with SLE and 20 healthy women participated
in the study. All participants were evaluated with actigraphy for a week and they
completed self-report instruments of sleep quality, quality of life, fatigue,
anxiety, depression and perceived stress. Comparison analyses between the two
groups were done using Chi-square and Student's t-tests. The association between
sleep quality and the remaining variables was explored using Pearson correlation
coefficients. RESULTS: SLE patients had higher fragmentation index in the
actigraphic analysis and a perception of poorer sleep quality, more fatigue,
anxiety and depression than the control group. Bivariate analyses showed that the
perception of more sleep disturbance and daytime dysfunction was associated with
a lower health-related quality of life, more fatigue, emotional discomfort and
more perceived stress. Also, the fragmentation index in the actigraphy was
significantly related to the perception of poorer quality of sleep. CONCLUSION:
SLE women had a poorer sleep quality (objective and subjective). These
alterations could play a modulatory role in clinical and psychological
manifestations of the disease and affect the quality of life in this population.
More research is needed to clarify these relations and to determine the potential
benefits of interventions directed to improve sleep in the clinical managing of
the patients with SLE.
PMID- 28425180
TI - American College of Cardiology 2017.
PMID- 28425179
TI - Resilience of the prokaryotic microbial community of Acropora digitifera to
elevated temperature.
AB - The coral is a holobiont formed by the close interaction between the coral animal
and a diverse community of microorganisms, including dinoflagellates, bacteria,
archaea, fungi, and viruses. The prokaryotic symbionts of corals are important
for host fitness but are also highly sensitive to changes in the environment. In
this study, we used 16S ribosomal RNA (rRNA) sequencing to examine the response
of the microbial community associated with the coral, Acropora digitifera, to
elevated temperature. The A. digitifera microbial community is dominated by
operational taxonomic unit (OTUs) affiliated with classes Alphaproteobacteria and
Gammaproteobacteria. The prokaryotic community in the coral tissue is distinct
from that of the mucus and the surrounding seawater. Remarkably, the overall
microbial community structure of A. digitifera remained stable for 10 days of
continuous exptosure at 32 degrees C compared to corals maintained at 27 degrees
C. However, the elevated temperature regime resulted in a decrease in the
abundance of OTUs affiliated with certain groups of bacteria, such as order
Rhodobacterales. On the other hand, some OTUs affiliated with the orders
Alteromonadales, Vibrionales, and Flavobacteriales, which are often associated
with diseased and stressed corals, increased in abundance. Thus, while the A.
digitifera bacterial community structure appears resilient to higher temperature,
prolonged exposure and intensified stress results in changes in the abundance of
specific microbial community members that may affect the overall metabolic state
and health of the coral holobiont.
PMID- 28425181
TI - Effects of different aerobic exercise frequencies on streptozotocin-nicotinamide
induced type 2 diabetic rats: Continuous versus short bouts and weekend warrior
exercises.
AB - BACKGROUND: Exercise training is known to have multiple beneficial effects on
type 2 diabetes mellitus (T2DM). The aim of this study was to explore the effects
of aerobic exercise frequency on diabetic parameters, the histopathological
structure of skeletal muscle, diabetic myopathy, and mitochondrial enzyme
activity in an experimental model of T2DM. METHODS: Sprague-Dawley rats (n = 35)
were rendered diabetic by injection of nicotinamide (110 mg/kg) and
streptozotocin (65 mg/kg). Rats with blood glucose concentrations between 7 and
17 mmol/L were used. Diabetic rats were randomly allocated to one of the
following groups: (i) control sedentary; (ii) diabetic sedentary; (iii) diabetic
with continuous exercise (30 min/day, 5 days/week); (iv) diabetic with short
bouts of exercise (3 * 10 min/day, 5 days/week); and (v) diabetic rats as
"weekend warriors" (35 + 40 min/day, 2 days/week). After 6 weeks swimming
exercise (total duration 150 min/week), biochemical tests were performed to
measure insulin, glucose, cytokines, serum and muscle myeloperoxidase (MPO), and
malondialdehyde (MDA) levels. Histologic analysis (histomorphometric and
mitochondrial enzyme analysis) was also performed. RESULTS: Compared with
diabetic sedentary rats, significant improvements were observed in all exercise
groups in terms of glucose levels, weight loss, tissue MPO and MDA levels,
muscular connective tissue, muscle atrophy, mitochondrial enzyme, and all
histomorphometric analyses. CONCLUSIONS: The results of the study emphasize the
effects of training on inflammation, increased oxidative stress, myopathy, and
mitochondrial damage in a rat model of T2DM, and demonstrate that there is no
major difference between exercise modalities provided that the total duration of
exercise remains the same.
PMID- 28425182
TI - Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a
systematic review.
AB - The aim of this review was to understand the landscape of serum ferritin in
diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron
deficiency in pregnancy is a major public health problem leading to the
development of anaemia. Reducing the global prevalence of anaemia in women of
reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the
gold standard test for iron deficiency but requires an invasive procedure;
therefore, serum ferritin is the most clinically useful test. We undertook a
systematic search of electronic databases and trial registers from inception to
January 2016. Studies of iron or micronutrient supplementation in pregnancy with
pre-defined serum ferritin thresholds were included. Two independent reviewers
selected studies, extracted data and assessed quality. There were 76 relevant
studies mainly of observational study design (57%). The most commonly used
thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and
<15 ng mL-1 (68%). Most primary studies provided no justification for the choice
of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by
expert consensus in a guideline development process. There were five studies (7%)
using a serum ferritin threshold defining iron deficiency derived from primary
studies of bone marrow aspiration. Unified international thresholds of iron
deficiency for women throughout pregnancy are required for accurate assessments
of the global disease burden and for evaluating effectiveness of interventions
addressing this problem.
PMID- 28425184
TI - Enantioselective Synthesis of (+)-Mitomycin K by a Palladium-Catalyzed Oxidative
Tandem Cyclization.
AB - The mitomycins, a family of bioactive natural products, feature a compact 6/5/5
fused polycyclic ring structure densely decorated with highly reactive and/or
fragile quinone, amino ketal, and aziridine as well as carbamate moieties. It is
this striking feature that has defeated numerous synthetic attempts towards these
apparently small molecules, rendering them one of the most formidable targets for
total synthesis. We herein report the first enantioselective synthesis of (+)
mitomycin K, a representative of G series mitomycins. The key step of this
synthesis is an enantioselective oxidative cyclization catalyzed by a
palladium/(+)-sparteine system that had previously been developed by our group.
The robustness of this method bodes well for further applications in the
asymmetric total synthesis of natural products, particularly those with
characteristic 6/5/5-fused pyrroloindole skeletons.
PMID- 28425183
TI - Associations between major life events and adherence, glycemic control, and
psychosocial characteristics in teens with type 1 diabetes.
AB - AIMS: This cross-sectional study assessed the type of major life events occurring
in a contemporary sample of teens with type 1 diabetes and the association
between event frequency and demographic, diabetes management, and psychosocial
characteristics. METHODS: Parents of 178 teens completed the Life Events
Checklist to report major events teens had experienced in the last year: 42%
experienced 0 to 1 event (n = 75), 32% experienced 2 to 3 events (n = 57), and
26% experienced 4+ events (n = 46). Teens and parents completed validated
measures of treatment adherence, diabetes-specific self-efficacy, quality of
life, and diabetes-specific family conflict. Parent-youth interview and chart
review provided demographics and diabetes management data. RESULTS: Mean number
of events/teen was 2.6 +/- 2.7 (range = 0-15). The most common events were
"Hospitalization of a family member" (24%), "Getting a bad report card" (20%),
"Serious arguments between parents" (19%), and "Serious illness/injury in a
family member" (19%). Compared with teens experiencing 0 to 1 event, teens
experiencing 4+ events were less likely to have married parents (P = .01) and a
parent with a college degree (P = .006). Teens with 4+ events had significantly
poorer adherence (P = .002 teen, P = .02 parent), lower self-efficacy (P = .03
teen, P < .0001 parent), poorer quality of life (P < .0001 teen, P < .0001
parent), and more conflict (P = .006 teen, P = .02 parent) than teens with fewer
events. In a multivariate model (R 2 = 0.21, P < .0001) controlling for
demographic and diabetes management characteristics, fewer events was associated
with lower A1c (P = .0009). CONCLUSIONS: Occurrence of more major life events was
associated with poorer diabetes care and A1c and more negative psychosocial
qualities in teens with type 1 diabetes.
PMID- 28425185
TI - The influence of hippocampal atrophy on the cognitive phenotype of dementia with
Lewy bodies.
AB - OBJECTIVE: The level of hippocampal atrophy in dementia with Lewy bodies (DLB) is
typically less than that observed in Alzheimer's disease (AD). However, it is not
known how the cognitive phenotype of DLB is influenced by hippocampal atrophy or
the atrophy of adjacent medial temporal lobe structures. METHODS: Dementia with
Lewy bodies (n = 65), AD (n = 76) and control (n = 63) participants underwent 3T
magnetic resonance imaging and cognitive Cambridge Cognitive Examination and Mini
Mental State Examination (CAMCOG and MMSE) assessments. Hippocampal volume, and
parahippocampal, entorhinal and temporal pole cortical thickness, was compared
between groups. Regression models were used to investigate whether hippocampal
volume and cortical thickness associated with global cognition and cognitive
subdomains. RESULTS: Dementia with Lewy bodies, AD and control participants
showed significantly different hippocampal, parahippocampal and entorhinal
cortical thinning, where atrophy was greatest in AD and intermediate in DLB.
Temporal pole thickness was reduced in DLB and AD compared with control
participants. In DLB, but not AD, hippocampal volume associated with total
CAMCOG, CAMCOG memory and MMSE scores. In DLB, parahippocampal, entorhinal and
temporal pole thickness associated with total CAMCOG and CAMCOG memory scores,
parahippocampal thickness associated with MMSE scores, and entorhinal thickness
associated with CAMCOG executive function scores. CONCLUSIONS: In this large
sample, these results are in agreement with other studies indicating that
hippocampal atrophy is less severe in DLB than AD. Hippocampal atrophy and medial
temporal lobe cortical thickness were associated with the severity of cognitive
symptoms, suggesting that atrophy in these structures, as a potential proxy of AD
pathology, may partly mediate specific DLB cognitive symptoms. (c) 2017 The
Authors. International Journal of Geriatric Psychiatry Published by John Wiley &
Sons Ltd.
PMID- 28425188
TI - Effects of age and viscosity on food transport and breathing-swallowing
coordination during eating of two-phase food in nursing home residents.
AB - AIM: When eating food that contains both liquid and solid phases, the liquid
component frequently enters the hypopharynx before swallowing and can increase
the risk of aspiration. Thus, we examined whether the initial viscosity of mixed
consistency food could alter pre-swallow food transport and breathing-swallowing
coordination in older adults. METHODS: Fiberoptic endoscopy was recorded while 18
healthy young adults and 19 older adults ate 5 g of steamed rice combined with 3
mL of blue-dye water. Liquid viscosity was set at three levels by the addition of
a thickening agent (0 wt%, thin; 2 wt%, thicker; 4 wt%, higher-viscosity,
respectively). We measured the timing of swallow initiation and its corresponding
respiratory phase for each participant. RESULTS: For thin mixed consistency food,
whereas the timing of swallow initiation was comparable between young and older
participants, swallowing was initiated during inspiration significantly more
often in older participants (31.6 %) than in young participants (5.6 %). In
contrast, the timing of swallow initiation was delayed in older participants for
thicker and higher-viscosity foods, although swallowing was commonly initiated
during expiration in both groups. CONCLUSIONS: In older adults, we observed that
swallow initiation function was preserved for thin mixed consistency samples, but
breathing-swallowing coupling was diminished. For higher-viscosity foods, swallow
initiation was delayed in this group, but breathing-swallowing coordination was
not disturbed, probably as a result of the slow bolus flow into the hypopharynx.
Thus, it appears the initial viscosity of mixed consistency food profoundly
affects food transport before swallowing as well as breathing-swallowing
coordination in nursing home residents. Geriatr Gerontol Int 2017; 17: 2171-2177.
PMID- 28425187
TI - Significance of measured intraoperative portal vein flows after
thrombendvenectomy in deceased donor liver transplantations with portal vein
thrombosis.
AB - Adequate portal vein (PV) flow in liver transplantation is essential for a good
outcome, and it may be compromised in patients with portal vein thrombosis (PVT).
This study evaluated the impact of intraoperatively measured PV flow after PV
thrombendvenectomy on outcomes after deceased donor liver transplantation (DDLT).
The study included 77 patients over a 16-year period who underwent PV
thrombendvenectomy with complete flow data. Patients were classified into 2
groups: high PV flow (>1300 mL/minute; n = 55) and low PV flow (<=1300 mL/minute;
n = 22). Postoperative complications and graft survival were analyzed according
to the PV flow. The 2 groups were similar in demographic characteristics. Low PV
flow was associated with higher cumulative rates of biliary strictures (P = 0.02)
and lower 1-, 2-, and 5-year graft survival (89%, 85%, and 68% versus 64%, 55%,
and 38%, respectively; P = 0.002). There was no difference in the incidence of
postoperative PVT between the groups (1.8% versus 9.1%; P = 0.19). No biliary
leaks or hepatic artery thromboses were reported in either group. By multivariate
analyses, age >60 years (hazard ratio [HR], 3.04, 95% confidence interval [CI],
1.36-6.82; P = 0.007) and low portal flow (HR, 2.31; 95% CI, 1.15-4.65; P = 0.02)
were associated with worse survival. In conclusion, PV flow <1300 mL/minute after
PV thrombendvenectomy for PVT during DDLT was associated with higher rates of
biliary strictures and worse graft survival. Consideration should be given to
identifying reasons for low flow and performing maneuvers to increase PV flow
when intraoperative PV flows are <1300 mL/minute. Liver Transplantation 23 1032
1039 2017 AASLD.
PMID- 28425186
TI - Association studies of low-frequency coding variants in nonsyndromic cleft lip
with or without cleft palate.
AB - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common
human birth defects with complex etiology. Although genome-wide association
studies have successfully identified a number of risk loci, these loci only
account for about 20% of the heritability of orofacial clefts. The "missing"
heritability may be found in rare variants, copy number variants, or
interactions. In this study, we investigated the role of low-frequency variants
genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip.
We performed two statistical tests, Sequence Kernel Association Test (SKAT) and
Combined Multivariate and Collapsing (CMC) method using two minor allele
frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding
variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of
NSCL/P. Low-frequency variants in other genes were associated with decreased risk
of NSCL/P. These results demonstrate that low-frequency variants contribute to
the genetic etiology of NSCL/P.
PMID- 28425189
TI - The Global Ethics Corner: foundations, beliefs, and the teaching of biomedical
and scientific ethics around the world.
AB - The profound advances in the biomolecular sciences over the last decades have
enabled similar advances in biomedicine. These advances have increasingly
challenged our abilities to deploy them in an equitable and ethically acceptable
manner. As such, it has become necessary and important to teach biomedical and
scientific ethics to our students who will become the researchers, medical
professionals, and global citizens of the future. As advances in the biosciences
and medicine are made, developed, and used across the globe, our survival on an
endangered planet requires global dialog and consensual action. To that end, a
group of us from around the world have come together to describe the differing
foundations of our ethical beliefs, and how ethical issues in biomedicine and in
science are described and confronted in our countries. We hope to show the
commonality in our beliefs and practices and to encourage readers from around the
world to contribute to a continuing discussion through a new section of the
journal, The Global Ethics Corner. (c) 2017 by The International Union of
Biochemistry and Molecular Biology, 45(5):385-395, 2017.
PMID- 28425190
TI - Identification of the novel HLA-B*27:147 allele by polymerase chain reaction
sequence-based typing.
AB - HLA-B*27:147 differs from HLA-B*27:04:01 by a single nucleotide substitution at
position 523 C>G.
PMID- 28425191
TI - Thank god it's Friday - sleep improved.
AB - The weekend is usually seen as a window of recovery. Thus, sleep before a day off
may be less impaired than that before a workday. However, very few
polysomnographical studies have investigated this hypothesis. Therefore, the aim
of the present study was to compare sleep before a workday with that before a
weekend. Seventeen teachers participated. Sleep was recorded with polysomnography
on one weekday night during the workweek, and on a workday (Friday) followed by a
day off. Sleep diaries and actigraphs were also used. Weekend sleep showed
delayed bedtime and time of rising, a longer total sleep time (45 min), increased
N3 and N1, and decreased N2 and REM. Sleep spindles were reduced. The results
remained after truncation to the shortest common sleep duration (5 h). The
increase in N3 from weekday sleep to Friday night sleep was positively correlated
with N1 change (r = 0.853, P <= 0.001), and negatively correlated with N2 change
(r = -0.614, P <= 0.001). Subjective ratings showed that weekend sleep was
associated with less awakening problems and lower subjective arousal during the
day. The authors concluded that weekend sleep was longer, and showed increased N3
and N1. The authors suggest that the N3 increase before the day off is a result
of lower stress, while the N1 increase may be an effect of sleep spindle
suppression via the increase of N3 (which would suppress sleep spindles), thus
reducing N2 and enhancing N1.
PMID- 28425192
TI - Soluble-HLA-E: A follow up biomarker in Takayasu arteritis, independent of HLA-E
genotype.
AB - AIM: Disease activity assessment in Takayasu arteritis (TA) is challenging. Human
leukocyte antigen E (HLA-E) is shed from endothelium into serum as a soluble
molecule (sHLA-E) in response to inflammation. We aimed to study: (i) utility of
sHLA-E as a biomarker of disease activity; and (ii) association of HLA-E
polymorphism rs1264457 with clinical disease in Asian-Indian TA patients.
MATERIALS AND METHODS: In phase-1, sHLA-E levels were estimated in sera of 50
consecutive TA patients at baseline visit and 27 healthy controls. Serial
estimations were performed in 27 of them. In phase-2, DNA of 150 TA patients and
264 healthy controls were genotyped for rs1264457 polymorphism. RESULTS: At
baseline visit, disease was classified as active, stable and grumbling in 23, 18
and nine patients, respectively. sHLA-E levels were higher in active TA (43;
interquartile range [IQR]: 25.3-64.6) pg/mL) than stable disease (12.9; IQR: 7.6
21.6 pg/mL) (P = 0.001). At first follow-up visit, sHLA-E levels were numerically
higher in active disease than stable disease (P = 0.06) but this trend was
blunted at second follow-up. sHLA-E levels increased in 54% versus 25% of
patients with persistently active/relapsing and persistent stable course,
respectively. rs1264457 polymorphism was not associated with susceptibility to TA
and did not affect sHLA-E levels. CONCLUSION: sHLA-E level is useful as a
biomarker of disease activity and course in TA patients. rs1264457 polymorphism
is neither associated with susceptibility nor did it influence sHLA-E levels in
TA.
PMID- 28425193
TI - Health-related quality of life outcomes from a contemporary prostate cancer
registry in a large diverse population.
AB - OBJECTIVE: To assess the health-related quality of life (HRQoL) of patients with
prostate cancer up to 24 months after treatment in a contemporary large diverse
population. PATIENTS AND METHODS: Patients with newly diagnosed prostate cancer
from March 2011 to January 2014 in our healthcare system were included. The
Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was administered
before treatment, and at 1, 3, 6, 12, 18, and 24 months after treatment up to
November 2014 for all methods of treatment. The Kruskall-Wallis test was used to
compare the distribution of each EPIC-26 domain score at each time point, and
mixed models were used to assess the overall scores over the period after
treatment. RESULTS: In all, 5 727 patients were included. There were data for 3
422, 2 329, 2 017, 1 922, 1 772, 1 260, and 837 patients before treatment, and at
1, 3, 6, 12, 18, and 24 months after treatment, respectively. At 1 month, bowel
scores were the lowest for patients that had had radiation therapy, and urinary
irritative symptoms were the lowest for those who had had brachytherapy. There
were sexual function declines for all the treatment methods, with surgery having
the steepest decline; open radical prostatectomy (ORP) had a greater decline than
robot-assisted laparoscopic prostatectomy (RALP). Patients who underwent RALP had
a better return of sexual function, approaching that of brachytherapy and
radiation therapy at 24 months. Urinary incontinence (UI) also declined the most
in surgical patients, with RALP patients improving slightly more than ORP
patients at 12-24 months. CONCLUSIONS: Patients' HRQoL after prostate cancer
treatment varies by treatment method. Notably, sexual function recovers most for
RALP patients. UI remains worse at 24 months after surgery, compared to other
methods of prostate cancer treatment.
PMID- 28425195
TI - Revolutionary reform in psychiatric care in Italy: The abolition of forensic
mental hospitals.
PMID- 28425194
TI - Unlocking the limitations: Living with chronic obstructive pulmonary disease and
receiving care through telemedicine-A phenomenological study.
AB - AIMS AND OBJECTIVES: To describe the lived experiences of quality of life among a
group of patients living with chronic obstructive pulmonary disease who were
included in a telemedical intervention after hospitalisation for disease
exacerbation. BACKGROUND: Patients with chronic obstructive pulmonary disease
have high symptom burden, poor control of symptoms and a need for greater
requirements in care. Telemedicine can provide benefits for patients with chronic
obstructive pulmonary disease by improving self-management. DESIGN: Descriptive
phenomenological approach. METHODS: Ten in-depth interviews were conducted with
chronic obstructive pulmonary disease patients participating in a telemedical
intervention. The collected data were analysed using a descriptive
phenomenological research method. RESULTS: Living with chronic obstructive
pulmonary disease was experienced as creating physical and mental limitations of
the diseased body and an increasing identity as a patient, which led to impaired
quality of life. Being included in the telemedicine intervention increased
accessibility to healthcare services and support from telemedicine nurses. Self
measurement of health data increased participants' clinical insight and created a
mutual clinical language in dialogue with telemedicine nurses, which led to
increased quality of life. However, receiving care through telemedicine was also
experienced as a dual chore. CONCLUSIONS: Telemedicine can reduce the perceived
limitations imposed by chronic obstructive pulmonary disease through four key
elements: (i) improving accessibility to healthcare services, (ii) increasing
support from health professionals, (iii) strengthening clinical insight and (iv)
developing a mutual clinical language, thus increasing quality of life. The
transparency facilitated through telemedicine in this healthcare context
encourages open decision-making, where the participants can increase their
knowledge and improve acknowledgement of and collaboration with telemedicine
nurses. RELEVANCE TO CLINICAL PRACTICE: Telemedicine can be beneficial when
rethinking care for chronic obstructive pulmonary disease by providing knowledge
on how living with chronic obstructive pulmonary disease can affect the
experience of receiving care through telemedicine and further determine for whom
telemedicine is useful.
PMID- 28425196
TI - Bad blood contaminating germline databases?
PMID- 28425197
TI - Once doesn't count: Phenotype-driven gene hunting in cohorts.
PMID- 28425198
TI - The cell adhesion molecule EphA4 is involved in circadian clock functions.
AB - Circadian (~24 h) rhythms of cellular network plasticity in the central circadian
clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal
network in the SCN regulates photic resetting of the circadian clock as well as
stability of the circadian system during both entrained and constant conditions.
EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling
connections of neurons and astrocytes, is expressed in the SCN. To address
whether EphA4 plays a role in circadian photoreception and influences the
neuronal network of the SCN, we have analyzed circadian wheel-running behavior of
EphA4 knockout (EphA4-/- ) mice under different light conditions and upon photic
resetting, as well as their light-induced protein response in the SCN. EphA4-/-
mice exhibited reduced wheel-running activity, longer endogenous periods under
constant darkness and shorter periods under constant light conditions, suggesting
an effect of EphA4 on SCN function. Moreover, EphA4-/- mice exhibited suppressed
phase delays of their wheel-running activity following a light pulse during the
beginning of the subjective night (CT15). Accordingly, light-induced c-FOS (FBJ
murine osteosarcoma viral oncogene homolog) expression was diminished. Our
results suggest a circadian role for EphA4 in the SCN neuronal network, affecting
the circadian system and contributing to the circadian response to light.
PMID- 28425199
TI - Asymmetric Total Synthesis of Hispidanin A.
AB - Asymmetric total synthesis of the dimeric diterpenoid hispidanin A was
accomplished by non-catalytic Diels-Alder cycloaddition at room temperature. The
synthesis relies on iron-catalyzed coupling to construct a Z-configured
trisubstituted alkene, an iron-catalyzed radical cascade to generate a labdane
type diene, and both Yamamoto cationic polyene cyclization and palladium
catalyzed Stille coupling to generate a totarane-type dienophile.
PMID- 28425200
TI - High-dose calcineurin inhibitor-free everolimus as a maintenance regimen for
heart transplantation may be a risk factor for Pneumocystis pneumonia.
AB - BACKGROUND: Everolimus reduces the incidence of cardiac-allograft vasculopathy
(CAV) and is less renally toxic than are calcineurin inhibitors (CNIs). We
evaluated the safety of CNI-free everolimus for post-heart transplant (HTx)
patients. METHODS: We retrospectively reviewed the records of 36 consecutive
patients who had undergone an HTx between January 2006 and December 2013 in
National Cheng Kung University Hospital. All patients initially had been treated
with the standard tacrolimus regimen. The Study group-12 patients with CAV, renal
impairment, or a history of malignancy-were switched from tacrolimus to
everolimus. The Control group consisted of 19 patients who remained on the
standard regimen. The target everolimus trough concentration was 8-14 ng/mL. The
primary outcome was survival, and the secondary outcomes were bacterial, viral,
fungal, and other infections; Pneumocystis jirovecii pneumonia (PJP); and
rejection (>=2R). RESULTS: During a 53.3+/-25.6-month follow-up, the survival
rate, rejection rate, and number of infections, except for PJP, were not
significantly different between the two groups. In the Study group, 6 patients
were diagnosed with PJP 33+/-18.2 months after switching. None of the Control
group patients were diagnosed with PJP during follow-up. CONCLUSIONS: A high-dose
CNI-free everolimus maintenance regimen might yield a higher incidence of post
transplantation PJP.
PMID- 28425201
TI - Numerical analysis of crimping and inflation process of balloon-expandable
coronary stent using implicit solution.
AB - The paper presents an applied methodology for numerical finite element analysis
of coronary stent crimping and the free inflation process with the use of a
folded noncompliant angioplasty balloon. The use of an implicit scheme is
considered as the most original part of the work, as an explicit finite element
procedure is very often preferred. Hitherto, when the implicit solution was used
for the finite element solution, the simulated issue was largely simplified.
Therefore, the authors focused on the modelling methodology with minimum possible
simplification, ie, a full load path (compression and inflation in single
analysis), solid element discretization, and sophisticated contact models (bodies
with highly different stiffness). The obtained results are partially compared
with experimental data (radial force during the crimping procedure) and present
satisfactory compliance. The authors believe that presented methodology allow for
significant improvement of the obtained results, as well as potential extension
of the research scope, compared to previous efforts performed using the explicit
integration scheme. Moreover, the presented methodology is believed to be
suitable for sensitivity and optimization studies.
PMID- 28425202
TI - Examining solutions to missing data in longitudinal nursing research.
AB - PURPOSE: Longitudinal studies are highly valuable in pediatrics because they
provide useful data about developmental patterns of child health and behavior
over time. When data are missing, the value of the research is impacted. The
study's purpose was to (1) introduce a three-step approach to assess and address
missing data and (2) illustrate this approach using categorical and continuous
level variables from a longitudinal study of premature infants. METHODS: A three
step approach with simulations was followed to assess the amount and pattern of
missing data and to determine the most appropriate imputation method for the
missing data. Patterns of missingness were Missing Completely at Random, Missing
at Random, and Not Missing at Random. Missing continuous-level data were imputed
using mean replacement, stochastic regression, multiple imputation, and fully
conditional specification (FCS). Missing categorical-level data were imputed
using last value carried forward, hot-decking, stochastic regression, and FCS.
Simulations were used to evaluate these imputation methods under different
patterns of missingness at different levels of missing data. RESULTS: The rate of
missingness was 16-23% for continuous variables and 1-28% for categorical
variables. FCS imputation provided the least difference in mean and standard
deviation estimates for continuous measures. FCS imputation was acceptable for
categorical measures. Results obtained through simulation reinforced and
confirmed these findings. PRACTICE IMPLICATIONS: Significant investments are made
in the collection of longitudinal data. The prudent handling of missing data can
protect these investments and potentially improve the scientific information
contained in pediatric longitudinal studies.
PMID- 28425203
TI - Educational and career goal attainments in young adult childhood cancer
survivors.
AB - PURPOSE: Examine the educational and career outcomes of young adult childhood
cancer survivors. DESIGN AND METHODS: Descriptive study design using a survey
sent to 336 survivors. Quantitative and qualitative data were analyzed
separately. RESULTS: Only 50 completed surveys were returned. Having a central
nervous system tumor and radiation were associated with physical impairments.
Four themes also emerged: future as medical professionals, dreams fallen short,
peer relationships, and positive outlook on life. PRACTICE IMPLICATIONS:
Pediatric nurses caring for survivors should partner with oncology professionals
to support survivors to enrich their educational and career opportunities.
PMID- 28425204
TI - Ten tips to improve the likelihood of manuscript acceptance for publication in
JSPN.
PMID- 28425205
TI - Engineering the xylose-catabolizing Dahms pathway for production of poly(d
lactate-co-glycolate) and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) in
Escherichia coli.
AB - Poly(lactate-co-glycolate), PLGA, is a representative synthetic biopolymer widely
used in medical applications. Recently, we reported one-step direct fermentative
production of PLGA and its copolymers by metabolically engineered Escherichia
coli from xylose and glucose. In this study, we report development of
metabolically engineered E. coli strains for the production of PLGA and poly(d
lactate-co-glycolate-co-d-2-hydroxybutyrate) having various monomer compositions
from xylose as a sole carbon source. To achieve this, the metabolic flux towards
Dahms pathway was modulated using five different synthetic promoters for the
expression of Caulobacter crescentus XylBC. Further metabolic engineering to
concentrate the metabolic flux towards d-lactate and glycolate resulted in
production of PLGA and poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) with
various monomer fractions from xylose. The engineered E. coli strains produced
polymers containing 8.8-60.9 mol% of glycolate up to 6.93 g l-1 by fed-batch
cultivation in a chemically defined medium containing xylose. Finally, the
biocompatibility of poly(d-lactate-co-glycolate-co-d-2-hydroxybutyrate) was
confirmed by live/dead assay using human mesenchymal stem cells.
PMID- 28425206
TI - Considering Tangible Benefit for Interdependent Donors: Extending a Risk-Benefit
Framework in Donor Selection.
AB - From its infancy, live donor transplantation has operated within a framework of
acceptable risk to donors. Such a framework presumes that risks of living
donation are experienced by the donor while all benefits are realized by the
recipient, creating an inequitable distribution that demands minimization of
donor risk. We suggest that this risk-tolerance framework ignores tangible
benefits to the donor. A previously proposed framework more fully considers
potential benefits to the donor and argues that risks and benefits must be
balanced. We expand on this approach, and posit that donors sharing a household
with and/or caring for a potential transplant patient may realize tangible
benefits that are absent in a more distantly related donation (e.g. cousin,
nondirected). We term these donors, whose well-being is closely tied to their
recipient, "interdependent donors." A flexible risk-benefit model that combines
risk assessment with benefits to interdependent donors will contribute to donor
evaluation and selection that more accurately reflects what is at stake for
donors. In so doing, a risk-benefit framework may allow some donors to accept
greater risk in donation decisions.
PMID- 28425207
TI - BCG vaccination-induced suppurative lymphadenitis: four signs to pay attention
to.
AB - Suppurative lymphadenitis is one of the severe complication after BCG
vaccination, but its diagnostic criteria and treatment guidelines have not yet
been established. In this article, we describe a case of suppurative
lymphadenitis caused by BCG vaccination and propose diagnostic criteria and
treatment guidelines of the disease. The lymphadenitis was presented as skin
involving mass and was completely extirpated. Pathological evaluation revealed a
necrotising lymphadenitis, consistent with the diagnosis of BCG lymphadenitis.
The patient was administered adjuvant medical treatment with anti-TB medications
(Isoniazid and Rifampicin) for 3 months. At 6 months follow-up, the disease was
in complete remission without complications. We recommend focus on the following
four signs when diagnosing BCG lymphadenitis: (i) previous history of vaccination
on the ipsilateral side of the lesion, (ii) absence of any other infection signs,
(iii) absence of fever and (iv) isolated axillary or supraclavicular/cervical
lymph node enlargement proven by ultrasonography or computed tomography scan. BCG
vaccination-induced suppurative lymphadenitis can easily be overlooked, but
prompt, accurate diagnosis followed by appropriate surgical resection should
result in complete healing as in this case.
PMID- 28425208
TI - Nitrogenase Cofactor: Inspiration for Model Chemistry.
AB - The cofactor of nitrogenase is the largest and most intricate metal cluster known
in nature. Its reactivity, mode of action and even the precise binding site of
substrate remain a matter of debate. For decades, synthetic chemists have taken
inspiration from the exceptional structural, electronic and catalytic features of
the cofactor and have tried to either mimic the unique topology of the entire
site, or to extract its functional principles and build them into novel catalysts
that achieve the same-or very similar-astounding transformations. We review some
of the available model chemistry as it represents the various approaches that
have been taken from studying the cofactor, to eventually summarize the current
state of knowledge on catalysis by nitrogenase and highlight the mutually
beneficial role of model chemistry and enzymology in bioinorganic chemistry.
PMID- 28425209
TI - Identification of dynamic load for prosthetic structures.
AB - Dynamic load exists in numerous biomechanical systems, and its identification
signifies a critical issue for characterizing dynamic behaviors and studying
biomechanical consequence of the systems. This study aims to identify dynamic
load in the dental prosthetic structures, namely, 3-unit implant-supported fixed
partial denture (I-FPD) and teeth-supported fixed partial denture. The 3
dimensional finite element models were constructed through specific patient's
computerized tomography images. A forward algorithm and regularization technique
were developed for identifying dynamic load. To verify the effectiveness of the
identification method proposed, the I-FPD and teeth-supported fixed partial
denture structures were investigated to determine the dynamic loads. For
validating the results of inverse identification, an experimental force-measuring
system was developed by using a 3-dimensional piezoelectric transducer to measure
the dynamic load in the I-FPD structure in vivo. The computationally identified
loads were presented with different noise levels to determine their influence on
the identification accuracy. The errors between the measured load and identified
counterpart were calculated for evaluating the practical applicability of the
proposed procedure in biomechanical engineering. This study is expected to serve
as a demonstrative role in identifying dynamic loading in biomedical systems,
where a direct in vivo measurement may be rather demanding in some areas of
interest clinically.
PMID- 28425210
TI - CORRIGENDUM: Commentary on Pharmacometrics for Immunotherapy.
PMID- 28425211
TI - Importance of cytological subclassification of thyroid nodules with Bethesda
category III cytology (AUS/FLUS) into architectural atypia only and nuclear
atypia: A prospective study.
AB - BACKGROUND: The objective of this study was to compare two cytological
subcategories of thyroid nodules with Bethesda category III initial cytology.
METHODS: This was a prospective study. All patients with thyroid nodules > 1 cm
were eligible and 98 patients with category III cytology were selected. Cytology
was subcategorized into architectural atypia only (AA, n = 45) and nuclear atypia
(NA, n = 53). All patients underwent a second fine-needle aspiration (FNA). Only
patients whose second cytology was benign and ultrasonography was non-suspicious
were not referred for surgery. In these patients, the nodules were considered
benign. RESULTS: The second FNA more frequently revealed "benign cytology" in the
AA subcategory (44.4% vs. 24.5% in the NA subcategory). The second cytology
suggested "follicular neoplasm" or was "suspicious for follicular neoplasm"
(category IV) in 5 patients (11.1%) of subcategory AA and was "suspicious for
malignancy" (category V) in 13 (24.5%) of subcategory NA. Finally, malignancy was
diagnosed in 15.5% of cases of subcategory AA and in 41.5% of subcategory NA.
Follicular carcinoma was more frequent in subcategory AA, while classical
papillary carcinoma was more frequent in subcategory NA. Excluding cases of the
noninvasive encapsulated follicular variant of papillary carcinoma, malignancy
was diagnosed in 11.1% of patients of subcategory AA and in 35.8% of subcategory
NA. CONCLUSIONS: The results showed that subclassification of the Bethesda
category III improves cancer risk prediction, with potential repercussions for
clinical practice. Diagn. Cytopathol. 2017;45:604-607. (c) 2017 Wiley
Periodicals, Inc.
PMID- 28425212
TI - Enantioselective Cascade Reaction for Synthesis of Quinolinones through
Synergistic Catalysis Using Cu-Pybox and Chiral Benzotetramisole as Catalysts.
AB - In contrast to the well-studied asymmetric catalyzed synthesis of
tetrahydroquinolines, the asymmetric methodologies toward 3,4-dihydroquinolin-2
ones are quite rare. Herein, the first asymmetric cascade reaction is reported
between ethynyl benzoxazinanones and mixed-anhydrides generated from aryl acetic
acids and pivaloyl chloride, based on synergistic catalysis. This allowed the
formation of attractive 3,4-dihydroquinolin-2-ones bearing two vicinal chiral
centers at C3 and C4 in high yields with excellent diastereo- and
enantioselectivities. A plausible chiral induction model for this reaction was
proposed. The utility of this methodology was exemplified by further elaboration
of the cyclization products by removal of the N-protecting groups.
PMID- 28425213
TI - Genotype-phenotype correlations in Cornelia de Lange syndrome: Behavioral
characteristics and changes with age.
AB - Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated
with unusual facial features, limb abnormalities, a wide range of health
conditions, and intellectual disability. Mutations in five genes that encode
(SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been
identified in up to 70% of individuals. Genetic cause remains unknown for a
proportion of individuals. There is substantial heterogeneity in all aspects of
CdLS but very little is known about what predicts phenotypic heterogeneity. In
this study, we evaluated genotype-phenotype associations in 34 individuals with
CdLS. Participants with NIPBL mutations had significantly lower self help skills
and were less likely to have verbal skills relative to those who were negative
for the NIPBL mutation. No significant differences were identified between the
groups in relation to repetitive behavior, mood, interest and pleasure,
challenging behavior, activity, impulsivity, and characteristics of autism
spectrum disorder whilst controlling differences in self help skills. Significant
correlations indicating lower mood, interest and pleasure, and increased
insistence on sameness with older age were identified for those who were NIPBL
mutation positive. The findings suggest similarities in the behavioral phenotype
between those with and without the NIPBL mutation once differences in self help
skills are controlled for. However, there may be subtle differences in the
developmental trajectory of these behaviors according to genetic mutation status
in CdLS.
PMID- 28425214
TI - Hypoglycemic and Antihyperglycemic Activities of Nine Medicinal Herbs Used as
Antidiabetic in the Region of Lubumbashi (DR Congo).
AB - The aim of this study was to assess the hypoglycemic and antihyperglycemic
activities of nine plants used as antidiabetic treatments in Lubumbashi and its
surroundings. Those are Albizia adianthifolia, Azanza garckeana, Cassia
occidentalis, Cassia sieberiana, Erythrina abyssinica, Gladiolus klattianus,
Rauvolfia caffra, Strychnos spinosa, and Vitex madiensis. Aqueous extracts,
obtained by decoction and maceration, were administered (500 mg/kg) per os to
guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral
glucose tolerance test (OGTT) conditions (glucose, 2 g/kg; follow-up over 210
min). For OGTT experiments, area under the curve of blood glucose levels, maximum
glucose concentration (Cmax), and time to reach Cmax (Tmax) were used to compare
test groups with the control conditions (glucose group). In hypoglycemic tests,
only three species induced significant (p < 0.001) lowering of normal glycemia:
A. adianthifolia (33% reduction), C. occidentalis (32%), and V. madiensis (43%);
in the same conditions, the positive control glibenclamide (6 mg/kg) induced a
blood glucose lowering of 55%. In OGTT conditions, all tested herbs were active,
with the highest inhibition of glycemia increases for V. madiensis (62%) and A.
adianthifolia (57%), compared with the hyperglycemic inhibition rate of
glibenclamide (50%). Oral glucose tolerance test conditions appear as essential
to detect the extracts most interesting for clinical use. These data support the
use of studied plants for diabetes treatment in traditional Congolese medicine
and indicate a good knowledge of tradipraticians in the field. Copyright (c) 2017
John Wiley & Sons, Ltd.
PMID- 28425215
TI - Lipid raft dynamics linked to sperm competency for fertilization in mice.
AB - It is well known that mammalian sperm acquires fertilization ability after
several maturation processes, particularly within the female reproductive tract.
In a previous study, we found that both glycosylphosphatidylinositol (GPI)
anchored protein (GPI-AP) release and lipid raft movement occur during the sperm
maturation process. In several genetic studies, release of GPI-AP is a crucial
step for sperm fertilization ability in the mouse. Here, we show that lipid raft
movement is also fundamental for sperm to be competent for fertilization by
comparing the sperm maturation process of two mouse inbred strains, C57BL/6 and
BALB/c. We found that ganglioside GM1 movement was exclusively reduced in BALB/c
compared with C57BL/6 among other examined sperm maturation parameters, such as
GPI-AP release, sperm migration to the oviduct, cholesterol efflux, protein
tyrosine phosphorylation and acrosome reaction, and was strongly linked to sperm
fertility phenotype. The relationship between GM1 movement and in vitro
fertilization ability was confirmed in other mouse strains, suggesting that lipid
raft movement is one of the important steps for completing the sperm maturation
process.
PMID- 28425216
TI - Pneumonia risk in asthma patients using inhaled corticosteroids: a quasi-cohort
study.
AB - AIM: Studies have linked the use of inhaled corticosteroids (ICSs) to excess
pneumonia risk in chronic obstructive pulmonary disease patients. The risk in
asthma patients remains unclear. The objective of the present study was to
examine the risk of pneumonia with ICSs in asthma patients aged 12-35 years.
METHODS: We formed a cohort of asthma patients treated from 1990 to 2007 using
Quebec health insurance databases. Subjects were considered currently exposed if
they had had an ICS dispensed within the 60 days prior to their pneumonia index
event or matched person-moment. Secondary analyses investigated the risk of
pneumonia according to ICS dose and type. Rate ratios (RRs) and rate differences
(RDs) were both estimated through a quasi-cohort approach. RESULTS: The cohort
included 152 412 subjects, of whom 1928 had a pneumonia event during follow-up.
There was an increased risk of pneumonia associated with current use of ICSs [RR
1.83; 95% confidence interval (CI) 1.57, 2.14] or an excess risk of 1.44 cases
per 1000 person-years (RD 1.44; 95% CI 1.03, 1.85). There was an excess pneumonia
risk with low doses (RR 1.60; 95% CI 1.06, 2.45), moderate doses (RR 1.53; 95% CI
1.12, 2.08) and high doses (RR 1.96; 95% CI 1.64, 2.34) of ICSs, and with
budesonide (RR 2.67; 95% CI 2.05, 3.49) and fluticasone (RR 1.93; 95% CI 1.58,
2.36), specifically relative to no use. When accounting for potential protopathic
bias, the risk with current use of ICSs was attenuated (RR 1.48; 95% CI 1.22,
1.78). CONCLUSION: ICS use in asthma patients appears to be associated with an
increased risk of pneumonia and is present for both budesonide and fluticasone.
PMID- 28425217
TI - The release of pro-inflammatory cytokines is mediated via mitogen-activated
protein kinases rather than by the inflammasome signalling pathway in
keratinocytes.
AB - Toll-like receptors (TLRs) are expressed in the skin and airway epithelial
tissues, which are the most important sites of host-pathogen interactions. TLRs
recognize the 3-D structures of pathogen-associated molecules and are therefore
useful markers of the innate immune response. Here, we investigated the role of
lipopolysaccharides and monosodium urate (MSU) crystals in the activation of the
TLR and NOD-like receptor (NLR) pathways in human keratinocytes. Analysis of the
inflammasome compounds revealed that NOD-like receptor P3 and TLR4, both of which
are components of inflammasome complexes involved in the activation of
interleukin (IL)-1beta, were not expressed in keratinocytes. Transcriptomic
analysis showed that the combination of MSU and lipopolysaccharide priming did
not elicit significant results compared to MSU treatment, which induced the
expression of TLR2, IL-6 and IL-8/chemokine (C-X-C motif) ligand 8 CXCL8 in the
keratinocyte cell line HaCaT. Furthermore, MSU promoted the phosphorylation of
extracellular signal-regulated kinase 1/2 and MAPK14/p38alpha mitogen-activated
protein kinases. We concluded that MSU stimulates a pro-inflammatory response in
keratinocytes via mitogen-activated protein kinase pathway to induce production
of IL-8/CXCL8 chemokine (C-X-C motif) ligand 8 and TLR2.
PMID- 28425218
TI - Recurrence of congenital heart defects among siblings-a nationwide study.
AB - Congenital heart defects (CHD) constitute the largest group of congenital
malformations. In most families, only one person has CHD; however, the risk of
CHD increases for children born into families already affected. In this study,
all births from 1994 through 2009 were identified in the Medical Birth Registry
of Norway, including supplemental information on CHD from clinical and
administrative registers, as part of the CVDNOR project. By using the unique
personal identification number of each parent we were able to link 16,078 pairs
of twins, 445,584 pairs of full siblings, and 106,840 pairs of half-siblings.
Sibling recurrence risk ratio (RRR) was calculated using CHD status in the oldest
sibling as exposure and CHD status in the younger sibling as outcome, adjusted
for year of birth, maternal age, and maternal diabetes. Among full sibling pairs
with CHD in the older sibling, the younger sibling had CHD in 4.1% compared to
1.1% of the pairs without CHD in the older sibling (adjusted RRR 3.6; 95%
confidence interval (CI) 3.1-4.1). In same-sex twins the RRR was 14.0 (95% CI
10.6-18.6), and in opposite-sex twins the RRR was 11.9 (95% CI 7.1-19.9). For
half-siblings the RRR was 1.5 (95% CI 0.8-2.8). When restricting to severe types
of CHD, the RRR was 6.9 (95% CI 4.9-9.8) for full siblings. In 50% of the pairs
with recurrent CHD, the siblings had similar types of CHD. The high relative risk
of recurrence indicates that familial risk factors are important in the etiology
of CHD.
PMID- 28425219
TI - Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer Cells
by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia hispanica).
AB - The multidrug resistance (MDR) phenotype is considered as a major cause of the
failure in cancer chemotherapy. The acquisition of MDR is usually mediated by the
overexpression of drug efflux pumps of a P-glycoprotein. The development of
compounds that mitigate the MDR phenotype by modulating the activity of these
transport proteins is an important yet elusive target. Here, we screened the
saponification and enzymatic degradation products from Salvia hispanica seed's
mucilage to discover modulating compounds of the acquired resistance to
chemotherapeutic in breast cancer cells. Preparative-scale recycling HPLC was
used to purify the hydrolysis degradation products. All compounds were tested in
eight different cancer cell lines and Vero cells. All compounds were noncytotoxic
at the concentration tested against the drug-sensitive and multidrug-resistant
cells (IC50 > 29.2 MUM). For the all products, a moderate vinblastine-enhancing
activity from 4.55-fold to 6.82-fold was observed. That could be significant from
a therapeutic perspective. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425220
TI - Associations between the Transsexual Voice Questionnaire (TVQMtF ) and self
report of voice femininity and acoustic voice measures.
AB - BACKGROUND: The Transsexual Voice Questionnaire (TVQMtF ) was designed to capture
the voice-related perceptions of individuals whose gender identity as female is
the opposite of their birth-assigned gender (MtF women). Evaluation of the
psychometric properties of the TVQMtF is ongoing. AIMS: To investigate
associations between TVQMtF scores and (1) self-perceptions of voice femininity
and (2) acoustic parameters of voice pitch and voice quality in order to evaluate
further the validity of the TVQMtF . A strong correlation between TVQMtF scores
and self-ratings of voice femininity was predicted, but no association between
TVQMtF scores and acoustic measures of voice pitch and quality was proposed.
METHODS & PROCEDURES: Participants were 148 MtF women (mean age 48.14 years)
recruited from the La Trobe Communication Clinic and the clinics of three doctors
specializing in transgender health. All participants completed the TVQMtF and 34
of these participants also provided a voice sample for acoustic analysis. Pearson
product-moment correlation analysis was conducted to examine the associations
between TVQMtF scores and (1) self-perceptions of voice femininity and (2)
acoustic measures of F0, jitter (%), shimmer (dB) and harmonic-to-noise ratio
(HNR). OUTCOMES & RESULTS: Strong negative correlations between the participants'
perceptions of their voice femininity and the TVQMtF scores demonstrated that for
this group of MtF women a low self-rating of voice femininity was associated with
more frequent negative voice-related experiences. This association was strongest
with the vocal-functioning component of the TVQMtF . These strong correlations
and high levels of shared variance between the TVQMtF and a measure of a related
construct provides evidence for the convergent validity of the TVQMtF . The
absence of significant correlations between the TVQMtF and the acoustic data is
consistent with the equivocal findings of earlier research. This finding
indicates that these two measures assess different aspects of the voice-related
experience. CONCLUSIONS & IMPLICATIONS: Evidence supporting the validity of the
TVQMtF is strong and indicates that it is a sound measure for capturing the MtF
woman's self-perceptions of her vocal functioning and how her voice impacts on
her everyday life.
PMID- 28425221
TI - Conceptualizing movement by expert Bobath instructors in neurological
rehabilitation.
AB - RATIONALE, AIMS, AND OBJECTIVES: Movement, a core aspect of physiotherapy
practice, and integral to the clinical reasoning process has undergone limited
theoretical development. Instead, research has focused on intervention
effectiveness embedded within the positivist paradigm. The purpose of this study
was to explore how expert neurorehabilitation therapists conceptualize movement
as part of their clinical reasoning. METHOD: A qualitative interpretive
descriptive approach consisting of stimulated recall using video-recorded
treatment sessions and in-depth interviews was used. Theoretical sampling was
used to recruit members of the International Bobath Instructors Training
Association (IBITA) who are recognized experts in neurorehabilitation. Interview
transcripts were transcribed verbatim. Data analysis was progressive, iterative,
and inductive. RESULTS: Twenty-two IBITA instructors from 7 different countries
volunteered to participate. They ranged in clinical experience from 12 to 40
years and instructor experience from 1 to 35 years. The conceptualization of
movement by the IBITA instructors involves the following elements: (1) movement
comprises the whole person and the whole body, not just individual body segments;
(2) active alignment of body segments is integral to movement performance; and
(3) efficient movement requires the relative integration of postural
control/stability and selective movement/mobility. CONCLUSIONS: The IBITA
instructors conceptualize movement from a person-centred perspective. The
integration of postural control and selective movement, with alignment and
variability as key components, forms the foundation of their understanding of
movement. Further investigation into the role of postural control in movement
recovery post central nervous system lesion is required. Likewise, the dimensions
of movement critical to the conceptualization of movement are not well understood
from the perspective of the physiotherapist or persons with neurological
impairments.
PMID- 28425222
TI - Class III antiarrhythmic drugs amiodarone and dronedarone impair KIR 2.1 backward
trafficking.
AB - Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias.
The subcellular level at which drugs interfere in trafficking pathways is largely
unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac
inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and
dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a
lesser extent dronedarone, causes serious adverse effects to several organs and
tissue types, including the heart. Both drugs have been described to interfere in
the late-endosome/lysosome system. Here we defined the potential interference in
KIR 2.1 backward trafficking by amiodarone and dronedarone. Both drugs inhibited
IK1 in isolated rabbit ventricular cardiomyocytes at supraclinical doses only. In
HK-KWGF cells, both drugs dose- and time-dependently increased KIR 2.1 expression
(2.0 +/- 0.2-fold with amiodarone: 10 MUM, 24 hrs; 2.3 +/- 0.3-fold with
dronedarone: 5 MUM, 24 hrs) and late-endosomal/lysosomal KIR 2.1 accumulation.
Increased KIR 2.1 expression level was also observed in the presence of Nav 1.5
co-expression. Augmented KIR 2.1 protein levels and intracellular accumulation
were also observed in COS-7, END-2, MES-1 and EPI-7 cells. Both drugs had no
effect on Kv 11.1 ion channel protein expression levels. Finally, amiodarone
(73.3 +/- 10.3% P < 0.05 at -120 mV, 5 MUM) enhanced IKIR2.1 upon 24-hrs
treatment, whereas dronedarone tended to increase IKIR2.1 and it did not reach
significance (43.8 +/- 5.5%, P = 0.26 at -120 mV; 2 MUM). We conclude that
chronic amiodarone, and potentially also dronedarone, treatment can result in
enhanced IK1 by inhibiting KIR 2.1 degradation.
PMID- 28425223
TI - Three families with mild PMM2-CDG and normal cognitive development.
AB - Congenital disorders of glycosylation (CDG) are caused by defective glycosylation
of proteins and lipids. PMM2-CDG is the most common subtype among the CDG. The
severity of PMM2-CDG is variable. Patients often have a recognizable phenotype
with neurological and multisystem symptoms that might cause early death. We
report six patients from three families who are diagnosed with a clinically mild
PMM2-CDG and have normal cognitive development. All these patients had delayed
gross motor skills with mild-to-moderate neurological findings. Cerebellar
hypoplasia was detected in all siblings for whom brain MRI was performed. In 5/6
children the Wechsler Intelligence Scale for Children (WISC) showed normal
cognitive development with full scale IQ scores ranging from borderline to
average. Four patients were diagnosed with PMM2-CDG at the age of 8 years or
later as their neurological symptoms were quite mild and they had been able to
participate in regular school programs. We report patients with
p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys genotypes which may cause
milder variants of PMM2-CDG.
PMID- 28425224
TI - Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat
posterior eye diseases.
AB - Effective drug delivery to the retina still remains a challenge due to ocular
elimination mechanisms and complex barriers that selectively limit the entry of
drugs into the eye. To overcome these barriers, frequent intravitreal injections
are currently used to achieve high drug concentrations in vitreous and retina.
However, these repetitive injections may result in several side effects. Recent
advancements in the field of nanoparticle-based drug delivery could overcome some
of these unmet needs and various preclinical studies conducted to date have
demonstrated promising results of nanotherapies in the treatment of retinal
diseases. Compared to the majority of commercially available ocular implants, the
biodegradable nature of most nanoparticles (NPs) avoids the need for surgical
implantation and removal after the release of the payload. In addition, the
sustained drug release from NPs over an extended period of time reduces the need
for frequent intravitreal injections and the risk of associated side effects. The
nanometer size and highly modifiable surface properties make NPs excellent
candidates for targeted ocular drug delivery. Studies have shown that
nanocarriers enhance the intravitreal half-life and thus bioavailability of a
number of drugs including proteins and peptides. In addition, they have shown
promising results in delivering genetic material to the retinal tissues by
protecting it from possible intravitreal degradation. This review covers the
various challenges associated with drug delivery to the posterior segment of the
eye, particularly the retina, and highlights the application of nanocarriers to
overcome these challenges in context with recent advances in preclinical studies.
WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article
is categorized under: Therapeutic Approaches and Drug Discovery > Emerging
Technologies Implantable Materials and Surgical Technologies > Nanomaterials and
Implants.
PMID- 28425225
TI - Green Processing of Lignocellulosic Biomass and Its Derivatives in Deep Eutectic
Solvents.
AB - The scientific community has been seeking cost-competitive and green solvents
with good dissolving capacity for the valorization of lignocellulosic biomass. At
this point, deep eutectic solvents (DESs) are currently emerging as a new class
of promising solvents that are generally liquid eutectic mixtures formed by self
association (or hydrogen-bonding interaction) of two or three components. DESs
are attractive solvents for the fractionation (or pretreatment) of lignocellulose
and the valorization of lignin, owing to the high solubility of lignin in DESs.
DESs are also employed as effective media for the modification of cellulose to
afford functionalized cellulosic materials, such as cellulose nanocrystals. More
interestingly, biomassderived carbohydrates, such as fructose, can be used as one
of the constituents of DESs and then dehydrated to 5-hydroxymethylfurfural in
high yield. In this review, a comprehensive summary of recent contribution of
DESs to the processing of lignocellulosic biomass and its derivatives is
provided. Moreover, further discussion about the challenges of the application of
DESs in biomass processing is presented.
PMID- 28425226
TI - A review of pediatric pulmonary hypertension with new guidelines.
AB - This study aims to review pediatric pulmonary hypertension (PH) by comparing the
guidelines of the European Society of Cardiology (ESC)/European Respiratory
Society (ERS), the American Heart Association (AHA)/American Thoracic Society
(ATS), and the European Pediatric Pulmonary Vascular Disease Network (EPPVDN).
All three sets of guidelines define PH as having a mean pulmonary artery pressure
of >=25 mmHg and accept the validity of the World Health Organization (WHO)
classification system. Every child with a high index of suspicion for PH should
undergo an initial work-up of chest X-rays, electrocardiography, and
echocardiography. The AHA/ATS guidelines emphasize the necessity of cardiac
catheterization and hemodynamic studies. As mentioned in the AHA/ATS guidelines,
the symptoms and tests that can detect PH include right ventricle failure, WHO
functional class, syncope, echocardiography findings, hemodynamic data, brain
natriuretic peptide (BNP)/N-terminal pro-BNP, the 6-min walk test, and
cardiopulmonary exercise tests. The EPPVDN guidelines refer to positive acute
vasoreactivity test results and growth as risk factors. All three guidelines
highlight the importance of treating and following affected children in
specialized centers and recommend calcium channel blockers as a first-line
treatment in children (aged >12 months) who have a positive acute vasoreactivity
test. Children with PH have distinct clinical features. In order to overcome the
controversies related to the optimal management of pediatric PH, well-designed
clinical studies should be carried out on a large cohort of affected children.
PMID- 28425227
TI - Primary Sjogren's syndrome in patients with celiac disease.
AB - BACKGROUND/AIM: Many autoimmune diseases occur concomitantly with celiac disease
(CD). We aimed to determine the frequency of Sjogren's syndrome (SS) in CD
patients based on SS-specific serology verified by minor labial salivary biopsy.
MATERIALS AND METHODS: Eight-two patients with CD were included in the study.
After examination for objective evidence of sicca complex, all patients were
tested for serological presence of rheumatoid factor (RF) and antinuclear
antibodies (ANAs) and for ANA profile. Minor labial salivary biopsy was performed
for patients with positive serology and/or clinical signs of SS. RESULTS: Of the
patients included, 24 (29.3%) had dry eye symptoms while 20 (24.4%) had dry mouth
symptoms. Dry eye was detected by Schirmer test in 10 patients (12.2%) and by
ocular staining score in only 2 patients (2.4%). All samples were negative for RF
while 12 (14.6%) samples were positive for ANAs. Of 82 patients with CD, the
diagnosis of SS was established in only one patient (1.2%), while one patient
(1.2%) was diagnosed with morphea and 4 patients (4.9%) were classified as having
undifferentiated connective tissue disease. CONCLUSION: The prevalence of SS in
CD is low, so there is no need for serologic screening of all patients with CD
for SS.
PMID- 28425228
TI - The effects of the chloride:sodium ratio on acid-base statusand mortality in
septic patients.
AB - BACKGROUND/AIM: Calculation of the chloride:sodium (Cl-:Na+) ratio is proposed to
enable a quick evaluation of the effect of Cl- and Na+ on the acid-base balance
in critically ill patients. In the present study, the relationship of the Cl-:Na+
ratio of septic patients with acid-base status and ICU mortality were
investigated. MATERIALS AND METHODS: In our two-center study, 434 patients who
were diagnosed with sepsis were included. The patients were divided into three
groups: low (<0.75), normal (>=0.75, <0.80), and high (>=0.80) Cl-:Na+ ratio
groups. Patients' demographic data, blood gas values, length of ICU stay, and ICU
mortality were recorded. RESULTS: In the low and high groups, ICU mortality was
significantly higher than in the normal group (29.3%, 37.1%) (P = 0.005). There
was a negative correlation between the Cl:Na+ ratio and each of HCO3-, standard
base excess, and PaCO2 (r2 = 0.21, r2 = 0.19, and r2 = 0.17) (P < 0.001 for
each). In the multivariate analysis, the ICU mortality was increased 2.6-fold
(1.2-5.8) by low Cl-:Na+ ratio (P = 0.019). CONCLUSION: The Cl-:Na+ ratio is a
useful parameter for showing the relationship between Cl- and Na+ and their
impact on acid-base status. Low Cl-:Na+ ratio at ICU admission can be used as a
prognostic indicator for increased ICU mortality in septic patients.
PMID- 28425229
TI - Association of B7-H4 gene polymorphisms in urothelial bladder cancer.
AB - BACKGROUND/AIM: We aimed to study polymorphisms of the B7-H4 gene in order to
evaluate a possible association in urothelial carcinoma, as it is highly
expressed in cancer tissues. MATERIALS AND METHODS: In this study B7-H4 gene
rs10754339, rs10801935, and rs3738414 SNPs were studied by PCR-RFLP method in
paraffin-embedded tumor specimens from 62 urothelial carcinoma patients and in a
control group including 30 patients without bladder cancer. RESULTS: We detected
that the rs10754339 polymorphism was more frequent in the cancer patients when
compared with the control group (P < 0.05). Only the rs3738414 polymorphism
showed a statistically significant difference in frequency between pathologic
diagnostic groups. CONCLUSION: The rs10754339 AA genotype distribution was found
to have a higher frequency whereas the rs3738414 AG genotype distribution was
lower in the bladder cancer group (P < 0.05). None of the genotype distributions
showed a significant difference from the control group for the rs10801935
polymorphism. We conclude that B7-H4 has the potential to be a useful prognostic
marker in urothelial carcinoma.
PMID- 28425230
TI - Attitudes, wishes, and needs of diabetes patients and their relatives: Turkish
data from the DAWN2 study.
AB - BACKGROUND/AIM: The DAWN2 (Diabetes Attitudes, Wishes, and Needs) study was
conducted in order to ascertain the wishes, needs, and attitudes of diabetes
patients, their relatives, and healthcare professionals. The study was conducted
across 17 countries, including Turkey, and its objective was to introduce
policies that could successfully meet these requirements. In this article, the
needs, wishes, and attitudes of diabetes patients and their relatives in Turkey
are compared with those from other countries. MATERIALS AND METHODS: Eighty
patients with type 1 diabetes, 426 patients with type 2 diabetes, and 126
relatives of patients with diabetes were included in the study. RESULTS:
Depression was common in individuals suffering from diabetes and the quality of
life was negatively affected. The primary concerns of diabetic individuals were
general hypoglycemic attacks, nocturnal hypoglycemia, and gaining weight.
Analysis of self-care activities showed that physical activity, foot care, and
frequency of blood glucose measurement were below average in Turkey as compared
to other countries. CONCLUSION: DAWN2 is the first study of its kind. The
problems and shortcomings related to diabetes care and management in Turkey are
once again revealed with this study, and important data and opportunities to
improve them are presented.
PMID- 28425231
TI - The relationship between physical fitness and falling risk and fear of falling in
community-dwelling elderly people with different physical activity levels.
AB - BACKGROUND/AIM: The aim of this research was to determine the effects of physical
activity level (PAL) and physical fitness on falling parameters in community
dwelling elderly people. MATERIALS AND METHODS: Seventy-six elderly people were
grouped as low PAL group (group 1, n: 38) and high PAL (group 2, n: 38) according
to their PAL scores. PAL was measured by the Physical Activity Scale for the
Elderly and muscle strength, muscle endurance, aerobic endurance, and flexibility
tests were applied; body mass index (BMI) was calculated for physical fitness
measurement. Fall assessment included falling risk (Berg Balance Scale), dynamic
balance (Time Up and Go Test), and fear of falling (FOF) (Falls Efficacy Scale)
evaluation. RESULTS: While physical fitness parameters except flexibility in
group 2 were significantly better than they were in group 1 (P < 0.05), no
significant difference was found between the groups with regard to fall
assessments (P ? 0.05). In both groups, while physical fitness parameters except
BMI showed a positive and low or medium significant correlation with falling risk
and FOF, the same fitness parameters showed a negative and low or medium
significant correlation with dynamic balance. CONCLUSION: The results show that
PAL may have an indirect effect on fall parameters by increasing physical
fitness.
PMID- 28425232
TI - Effect of familial Mediterranean fever on sexual and reproductive health in
women.
AB - BACKGROUND/AIM: The aim of this study was to investigate the relationship between
familial Mediterranean fever and female sexual dysfunction and premenstrual
syndrome. MATERIALS AND METHODS: This study included 36 patients with familial
Mediterranean fever and 33 healthy volunteers. Familial Mediterranean fever was
diagnosed according to the Tel Hashomer criteria and familial Mediterranean fever
mutations were identified in all of the patients. The patients and healthy
volunteers were compared in terms of anxiety, depression, sexual dysfunction, and
premenstrual syndrome, and a model was created that describes the relationships
among these variables. RESULTS: We found statistically significant differences
between the groups in terms of anxiety, premenstrual syndrome, and Golombok Rust
Inventory of Sexual Satisfaction frequency and vaginismus subscale scores. There
was no difference in depression scores between the groups. CONCLUSION: Familial
Mediterranean fever is a rheumatic disease that predisposes patients to sexual
dysfunction and premenstrual syndrome, which emerges as direct and indirect
psychological factors.
PMID- 28425233
TI - Comparison of the standard GnRH antagonist protocol and the luteal phase
estradiol/GnRH antagonist priming protocol in poor ovarian responders.
AB - BACKGROUND/AIM: The aim of the study was to compare the luteal estradiol
patch/GnRH antagonists priming protocol (LPP) with the standard GnRH antagonist
protocol in poor ovarian responders (PORs) in terms of the outcomes of in vitro
fertilization (IVF) treatment. MATERIALS AND METHODS: IVF outcomes of 265 cycles
in 265 patients (106 in the LPP group, 159 in the standard GnRH antagonist group)
were evaluated retrospectively. RESULTS: Mean length of stimulation (11.4 +/- 2.7
vs. 10.0 +/- 2.7 days; P < 0.05) and the total gonadotropin dose (3403 +/- 1060
vs. 2984 +/- 1112) used were significantly greater in the LPP group than in the
standard GnRH antagonist protocol group. The mean number of oocytes retrieved
(3.5 +/- 2.6 vs. 3.7 +/- 2.8), the number of mature oocytes (2.8 +/- 2.2 vs. 2.6
+/- 2.2), fertilization rates (65% vs. 62%), the number of embryos transferred
(1.6 +/- 0.6 vs. 1.7 +/- 0.6), and implantation rates (16% vs. 13%) were similar.
The cancellation rate did not significantly differ between the groups (9.4% vs.
13.2%). There were no significant differences in the clinical pregnancy (11.3%
vs. 13.2%) or live birth rates per patient (3.8% vs. 9.4%) and clinical pregnancy
(18.8% vs. 22.6%) or live birth rates per embryo transfer (6.3% vs. 12.9%)
between the groups. CONCLUSION: LPP does not improve IVF outcomes when compared
with the standard GnRH antagonist protocol in PORs.
PMID- 28425234
TI - Alpha-1 Antitrypsin Levels and Polymorphisms in Interstitial Lung Diseases.
AB - BACKGROUND/AIM: Alpha-1 antitrypsin deficiency may be a potential predisposing
factor for interstitial lung fibrosis. We investigated alpha-1 antitrypsin levels
and its polymorphisms in patients with interstitial lung disease. MATERIALS AND
METHODS: A total of 103 interstitial lung disease patients were compared.
RESULTS: The mean alpha-1 antitrypsin level in idiopathic interstitial pneumonia
patients was 1.67 +/- 0.33 g/L, and it was 1.54 +/- 0.37 g/L in patients with
nonidiopathic interstitial pneumonia (P = 0.13). Low alpha-1 antitrypsin levels
were more frequently observed in nonidiopathic interstitial pneumonia patients
compared with idiopathic interstitial pneumonia, but the difference was not
statistically significant (8.9% vs. 0%, respectively, P = 0.4). In 100 patients,
the normal PiMM genotype was detected, while abnormal ones (PiMZ, n = 2, 1.9%;
PiMS, n = 1, 0.97%) were determined in three cases. When the frequency of alpha-1
antitrypsin polymorphism in interstitial lung disease patients was compared with
the data of the healthy population, no significant difference was detected for
the PiMZ and PiMS variants (P = 0.15 and P = 0.44, respectively). CONCLUSION:
Lower levels of serum alpha-1 antitrypsin were more frequent in nonidiopathic
interstitial pneumonia patients than idiopathic interstitial pneumonia without an
increase in genetic polymorphism. The difference was not statistically
significant.
PMID- 28425235
TI - A study on the validity and reliability of the Amblyopia andStrabismus
Questionnaire (A&SQ) in Turkish.
AB - BACKGROUND/AIM: This study aims to evaluate the reliability and validity of the
Amblyopia and Strabismus Questionnaire (AandSQ) that is translated into Turkish.
MATERIALS AND METHODS: This is a methodological study. A total of 149 patients
took part in the survey research between December 2012 and June 2014 in an
university hospital, and 37 were retested. Cronbach's alpha coefficient was used
for the questionnaire's reliability analysis. RESULTS: Cronbach's alpha
coefficients for the subscales of fear of losing the better eye, distance
estimation, visual disorientation, double vision, and social contact and
appearance were found to be 0.80, 0.88, 0.95, 0.80, and 0.81, respectively. Five
factors determined by the exploratory factor analysis explained 69.87% of the
total variance. CONCLUSION: The Turkish version of the AandSQ is found as a
reliable and valid scale for analyzing Turkish society. The AandSQ might be
helpful for measuring quality of life in patients with strabismus.
PMID- 28425236
TI - Predictors of health related quality of life in childhood epilepsy and comparison
with healthy children: findings from an Indian study.
AB - BACKGROUND/AIM: Children with epilepsy have reduced health-related quality of
life (HRQOL) due to disease and medications. We aimed to assess child-reported
HRQOL in Indian children with epilepsy and compare it with that in healthy
children. MATERIALS AND METHODS: A cross-sectional study of 256 children with
epilepsy aged between 5 and 18 years on antiepileptic drug (AED) treatment for at
least 3 months was performed and 125 age and sex matched healthy children were
included. A generic version of the Pediatric Quality of Life (PedsQL version 4)
scale was used to assess HRQOL. RESULTS: Children with epilepsy had diminished
scores in total score and all subdomains of PedsQL as compared to healthy
children. Children with epilepsy on polytherapy had diminished HRQOL compared
with those on monotherapy. Children with generalized seizures or with symptomatic
epilepsy had diminished HRQOL. Significant predictors of poor HRQOL were adverse
drug reactions (ADRs) to AED, polytherapy, longer duration of epilepsy, shorter
seizure-free interval, and seizure frequency. CONCLUSION: Children with epilepsy
have diminished HRQOL than healthy children in all subdomains of PedsQL.
Significant predictors are ADRs to AED, polytherapy, longer duration of epilepsy,
shorter seizure-free interval, and seizure frequency. Comprehensive management of
children with epilepsy must go beyond seizure control.
PMID- 28425237
TI - The efficacy of narrowband UVB treatment in pediatric vitiligo: a retrospective
analysis of 26 cases.
AB - BACKGROUND/AIM: Narrowband UVB (Nb UVB) treatment is commonly used for the
management of psoriasis and atopic dermatitis, and is less often used for
vitiligo in children. The aim of this study was to evaluate the efficacy and
short-term safety of Nb UVB phototherapy in children diagnosed with vitiligo
retrospectively. MATERIALS AND METHODS: A total of 26 patients younger than 18
years with the diagnosis of vitiligo and managed with Nb UVB phototherapy as
documented in archive records were evaluated. Clinical response was assessed
according to repigmentation of the lesions: good response when there was more
than 75% repigmentation, moderate response when there was 25%-74% repigmentation,
poor response when repigmentation was less than 24%, and unresponsive when there
was no pigmentation and new lesions occurred. RESULTS: A total of 26 patients
received Nb UVB treatment; 14 were girls and 12 were boys. The age at onset of
the disease varied between 2 and 18 years, with a mean age of onset of 10.07 +/-
4.53 years. Repigmentation rate of >75% was detected in 45.4% of cases.
CONCLUSION: Nb UVB phototherapy seems to be a well-tolerated effective and safe
treatment option in children, especially those unresponsive to topical treatment
and those with widespread lesions. However, long-term risks such as
photocarcinogenesis and photoaging should kept in mind.
PMID- 28425238
TI - Depression and Parkinson disease: prevalence, temporal relationship, and
determinants.
AB - BACKGROUND/AIM: Comorbidity of depression in Parkinson disease (PD) is a major
factor that changes patients' quality of life. However, the neurobiological and
sociodemographic risk factors for this comorbidity are not well studied. In this
study, we aimed to define the prevalence, temporal relationship, and psychosocial
and clinical determinants of depression comorbid with PD. MATERIALS AND METHODS:
Fifty-five PD patients were evaluated with SCID, a data form that assessed
sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the
Apathy Evaluation Scale. RESULTS: Depression (lifetime: 45.5%, last month: 25.5%,
before PD: 20%) was the most frequent psychiatric diagnosis. The major
determinants of depression in the last month and depression before PD were early
onset of PD and young age. Patients on pramipexole treatment were less likely to
be diagnosed with depression in the last month. Other sociodemographic and PD
related variables were not significantly different for lifetime, last month, and
pre-PD depression diagnosis compared to their counterparts. CONCLUSION:
Depression is prevalent both before and after patient gets a PD diagnosis.
Depression is not only the result of PD-related life changes but it is also a
preceding factor that may decrease the age of PD onset.
PMID- 28425239
TI - An 8-week thoracic spine stabilization exercise program improves postural back
pain, spine alignment, postural sway, and core endurance in university students:a
randomized controlled study.
AB - BACKGROUND/AIM: To investigate the effects of an 8-week thoracic stabilization
exercise program on back pain, spinal alignment, postural sway, and core
endurance in university students. MATERIALS AND METHODS: University students were
randomly allocated into exercise (n: 28) and control (n: 25) groups. The exercise
program was carried out 3 days a week for 8 weeks. Postural pain, spinal
alignment, postural sway, and core endurance were assessed via visual analogue
scale, Spinal Mouse, Biodex Balance System, and McGill's trunk muscle endurance
tests at the baseline and after 8 weeks of training. RESULTS: Differences were
observed for postural pain, thoracic and lumbar curvature, dynamic stability
index (eyes closed), and core endurance scores in the exercise group between
baseline and week 8 (P < 0.05) and all the parameters were significantly
different when compared to those of the control group (P < 0.05). CONCLUSION: The
program decreased postural pain, spinal curvatures, and postural sway, and
increased core endurance in university students. The program can be effective in
postural pain and misalignment of spine problems related to core weakness and
balance disorders.
PMID- 28425240
TI - Oral lichen planus: a 4-year clinical follow-up study.
AB - BACKGROUND/AIM: This study aimed to examine oral lichen planus (OLP) cases
histopathologically and cytologically, describe different clinical aspects of OLP
manifestations, and associate different OLP clinical forms with self-reported
oral health and with local and systemic risk factors. MATERIALS AND METHODS: All
patients with a referral diagnosis of OLP received biopsies. The histological
evaluation assessed infiltration with lymphocytes, epithelial hyperplasia, and
hyperkeratosis. Histology was used to validate the OLP diagnosis and to evaluate
the malignant transformation of OLP lesions. Clinical manifestations of OLP and
potential local oral environment-related risks were clinically assessed. Systemic
risks were evaluated by a structured questionnaire. RESULTS: A total of 133
patients with a histologically confirmed OLP diagnosis were followed. There were
more females (N = 109) than males (N = 24) and the majority of patients were
older than 50 years. The reticular form (45.1%) was the most prevalent clinical
form followed by the erosive-ulcerative form (33.8%). The histological
characteristics were most pronounced in the erosive-ulcerative form. Of the OLP
cases, 2.3% had a malignant transformation. CONCLUSION: Reticular and erosive
ulcerative were the most prevalent OLP forms. There were more female than male
OLP patients. Except for medication use, there were no statistically significant
differences among different clinical OLP forms in either local or systemic risk
factor distributions.
PMID- 28425241
TI - Incidence of cancer in the Turkish Republic of Northern Cyprus.
AB - BACKGROUND/AIM: This study analyzed the incidence, trends, and common types of
cancer in the Turkish Republic of Northern Cyprus (TRNC). MATERIALS AND METHODS:
This study is based on data collected from the office of the North Cyprus Cancer
Registry, Ministry of Health, for 2007-2012. Data were arranged on the basis of
age group, sex, and cancer site. Age standardized incidence rates (ASRs) were
estimated with the world standard population. EVIEWS (version 9) software was
used for statistical analysis. RESULTS: Of 1395 registered cases, 52.33% (730)
were reported in men and 47.67% (665) in women. The crude incidence rate was
96.41 in men and 101.74 in women. The average annual ASR was 88.88 in men and
87.76 in women with the cumulative rate of 21.47% and 14.69% in men and women,
respectively. The most common cancers in men were skin (ASR 15.62), prostate (ASR
11.23), bladder (ASR 11.71), lung (ASR 8.01), and colorectal cancer (ASR 7.61),
while in women these were breast (ASR 24.07), thyroid (ASR 14.93), skin (ASR
10.75), colorectal (ASR 6.05), and lymphoma (ASR 4.79). Linear regression
analysis confirmed rising trends for both men's (10.79, P <= 0.03) and women's
(14.67, P <= 0.04) cancers. CONCLUSION: Our findings revealed an increasing trend
of cancer incidence in the TRNC. For control and prevention, public awareness of
the risk factors and proper screening programs should be recommended.
PMID- 28425242
TI - Evaluation of serum uric acid levels in psoriasis vulgaris.
AB - BACKGROUND/AIM: Psoriasis has been accepted as a systemic disease and it is known
to be associated with various disorders including metabolic syndrome. High serum
uric acid levels are also associated with the components of metabolic syndrome.
In this study, we aimed to determine serum uric acid levels in patients with
psoriasis and the association of uric acid levels with disease activity by taking
the presence of metabolic syndrome criteria into account, since it is one of the
most important factors that affect serum uric acid levels. MATERIALS AND METHODS:
In this cross-sectional study, we evaluated 70 psoriasis patients and 70 healthy
individuals who were matched with the patients according to the presence of
metabolic syndrome. We evaluated the demographic features, levels of serum uric
acid, Psoriasis Area Severity Index (PASI) scores, presence of psoriatic
arthritis, nail involvement, and metabolic syndrome criteria of the patients.
RESULTS: Serum uric acid levels of psoriasis patients were significantly higher
than those of controls. There was a positive correlation between PASI scores and
serum uric acid levels of the patients. CONCLUSION: As hyperuricemia had a close
relationship with psoriasis and PASI scores, we suggest monitoring patients with
psoriasis for serum uric acid levels during treatment and follow-up.
PMID- 28425243
TI - The assessment of work productivity and activity impairment in Behcet's disease.
AB - BACKGROUND/AIM: The aim of this study was to assess the relationships between the
course of Behcet's disease (BD), disease-specific fears, and work productivity
and activity impairment. MATERIALS AND METHODS: In this cross-sectional study,
110 consecutive BD patients were included. The Work Productivity and Activity
Impairment questionnaire was used. RESULTS: In the group of employed patients,
30.41% had missed work during the previous week. The mean percentages of daily
activity impairment were higher in patients with musculoskeletal involvement
(39.81 +/- 33.61%) compared to those without (23.48 +/- 32.45%) (P = 0.008). A
greater decrease in working hours was observed in patients with eye involvement
(45.52 +/- 15.29 h) compared to those without (54.15 +/- 15.29 h) (P = 0.007).
More of the male patients (67.8%) were afraid of losing their jobs compared to
females (30%) (P = 0.000). CONCLUSION: The highest levels of lost productivity
and the most severe effects on daily life are consequences of eye and
musculoskeletal involvement in the study population. More effective therapeutic
approaches are required to improve the working lives of patients with BD.
Moreover, male patients had a higher fear of losing their jobs, suggesting a
match between the expected clinical course and the predictions of BD patients.
PMID- 28425244
TI - Genetic association analysis of ERBB4 polymorphisms with the risk ofschizophrenia
susceptibility in a Jordanian population of Arab descent.
AB - BACKGROUND/AIM: The ERBB4 gene encodes a transmembrane tyrosine kinase and is
considered to be one of the risk genes of schizophrenia. Although there is
evidence of the roles of genes and the environment in the etiology of
schizophrenia, a comprehensive biological and genetic background of the disease
is still lacking. The aim of this study is to assess whether genetic variation in
the human ERBB4 gene is associated with vulnerability to schizophrenia in the
Jordanian Arab population. MATERIALS AND METHODS: A total of 185 inpatients with
schizophrenia participated in this study and 195 healthy genetically homogeneous
individuals were also used as controls. Two genetic variants, rs839523 (G/A,
intron 2) and rs3748962 (A/G, exon 27), encompassing the ERBB4 gene were
genotyped using DNA sequencing. RESULTS: The results revealed a strong and
statistically significant genetic association of rs839523 with schizophrenia (P =
0.002 for allele and P = 0.006 for genotype). CONCLUSION: This study provides
strong statistical evidence that there is an association between the ERBB4 gene
and schizophrenia in a Jordanian population of Arab descent.
PMID- 28425245
TI - Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome
in advanced nonsmall cell lung cancer patients.
AB - BACKGROUND/AIM: The association between polymorphisms of xenobiotic/drug
metabolizing enzymes and TP53 and response to chemotherapy and survival of
patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In
this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro)
polymorphisms and response to platinum-based chemotherapy and survival in 137
advanced stage NSCLC patients were investigated. MATERIALS AND METHODS: Genetic
polymorphism analyses were determined by polymerase chain reaction (PCR) coupled
with restriction fragment length polymorphism (RFLP). RESULTS: The patients with
TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those
with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed
these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser),
GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1
polymorphic genes that we have previously genotyped in the same patients (Ada et
al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that
adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53
(Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as
compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016).
CONCLUSION: These results show that combined variant genotypes of TP53 (Arg72Pro,
Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival
in NSCLC patients.
PMID- 28425246
TI - Repeated prevalence studies of nosocomial infections in one university hospital
in Serbia.
AB - BACKGROUND/AIM: Nosocomial infections occur worldwide and affect both developed
and resource-poor countries. The aim of this paper was to determine the
prevalence and risk factors for nosocomial infections in one Serbian hospital.
MATERIALS AND METHODS: Three-point prevalence surveys were conducted in the
Clinical Center of Kragujevac (1240 beds). The standard definitions for
nosocomial infections of the Centers for Diseases Control and Prevention were
used. The authors conducted surveys according to the same protocol. RESULTS: The
prevalence of infected patients and the overall prevalence of nosocomial
infections was 6.2% and 7.1% in 2003, 4.6% and 4.6% in 2005, and 7.6% and 8.7% in
2009, respectively. In all three studies, the risk factors for nosocomial
infections were older age, intravascular catheters, urinary catheters, longer
hospital stays, hospitalization in an intensive care unit, and surgeries.
According to the multivariate regression analysis, a prolonged hospitalization
and use of a urinary catheter were independent risk factors for nosocomial
infections in the first and second study. CONCLUSION: The overall healthcare
associated infection prevalence in our hospital increased from 2003 to 2009, and
this was an incentive for a better definition of infection control priorities in
high-risk departments.
PMID- 28425247
TI - Meloxicam and diclofenac do not change VEGF and PDGF-ABserum levels of platelet
rich plasma.
AB - BACKGROUND/AIM: Platelet-rich plasma (PRP) application has gained widespread
interest for musculoskeletal injuries. Nonsteroidal antiinflammatory drugs are
frequently used in sports medicine before and/or after PRP application. Our study
seeks to determine whether serum levels of platelet-derived growth factor-AB
(PDGF-AB) and vascular endothelial growth factor (VEGF) levels of PRP would be
affected by nonsteroidal antiinflammatory drugs. MATERIALS AND METHODS: Two
different final concentrations of diclofenac (0.5 MUg mL-1 and 2.5 MUg mL-1),
meloxicam (0.8 MUg mL-1 and 2.0 MUg mL-1), and acetylsalicylic acid (final
concentration 450 MUm) were obtained in separate tubes with PRPs prepared from 20
healthy male volunteers. Medicine-free PRP was the control group. Growth factors
were measured using ELISA. RESULTS: PDGF-AB and VEGF serum levels did not change
with diclofenac, meloxicam, or acetylsalicylic acid addition. PDGF-AB and VEGF
serum levels correlated with each other. CONCLUSION: Diclofenac, meloxicam, and
acetylsalicylic acid did not affect PDGF-AB and VEGF serum levels.
PMID- 28425248
TI - The effect of transcatheter aortic valve implantation on mean platelet volume.
AB - BACKGROUND/AIM: Transcatheter aortic valve implantation (TAVI) is an innovative
approach to the treatment of aortic stenosis (AS) as an alternative to surgery in
high-risk patients. Mean platelet volume (MPV) is considered an indicator of
endothelial dysfunction, platelet function, and activation. In this study, we
aimed to investigate MPV changes in patients undergoing TAVI. MATERIALS AND
METHODS: This study included 100 patients diagnosed with symptomatic severe AS
and treated with TAVI between July 2011 and August 2013. Hematological parameters
of the patients were examined prior to the procedure and 24 h, 1 month, and 6
months after TAVI. RESULTS: A statistically significant change in patients' MPV
was detected after TAVI compared to the baseline situation (P: 0.001). While no
statistically significant change was observed on the first day after TAVI, at
discharge, compared to the baseline situation, a statistically significant
decrease was seen 1 month and 6 months after discharge. CONCLUSION: We have
demonstrated a decrease in MPV after surgery compared to the value before
surgery. We have sought to propound the change in MPV as an indication of
endothelial function after TAVI.
PMID- 28425249
TI - Prediction of atopy via total immunoglobulin E levels andskin prick tests in
patients with psoriasis.
AB - BACKGROUND/AIM: Although the etiopathogeneses of psoriasis and atopy appear to be
different, psoriasis has been found to be associated with atopy and atopic
dermatitis. In this study, we aimed to determine the role of atopy by examining
the medical history and clinical and laboratory findings of patients with
psoriasis. MATERIALS AND METHODS: Patients with psoriasis, asthma patients, and
healthy volunteers were included in the study. Serum total immunoglobulin E (IgE)
levels were obtained, and prick tests were administered to all groups. RESULTS:
Psoriatic patients demonstrated percentages of atopy history (21.3%) that were
higher than those of the healthy subjects (15.7%). The median total IgE level in
psoriatic patients was found to be statistically higher than that in the healthy
control group (P > 0.05). With respect to mite positivity, there were
statistically significant differences in the psoriatic (P < 0.05) and asthmatic
groups (P < 0.001) when compared to the healthy control group. CONCLUSION: Our
study is the first to use skin prick tests with psoriatic patients. Skin prick
test sensitivity to mites increased in psoriatic patients, and we believe that
this finding may be useful in protecting psoriatic patients from activation of
psoriasis and in determining the appropriate treatment approach.
PMID- 28425250
TI - Retrospective analysis of maternal, fetal, and neonatal outcomesof intrahepatic
cholestasis of pregnancy at Gazi University.
AB - BACKGROUND/AIM: Maternal, fetal, and neonatal outcomes in parturients with
intrahepatic cholestasis of pregnancy (ICP) have been retrospectively documented.
We aimed to present pregnancy outcomes of parturients with ICP who underwent
delivery. The study was conducted during a 1-year period. MATERIALS AND METHODS:
After ethics committee approval, data from 1 January to 31 December 2015 were
collected to identify parturients with ICP. RESULTS: Ten out of 37 patients
underwent normal spontaneous vaginal delivery (NSVD), and the remaining 27
parturients underwent cesarean section (CS). Five of 27 parturients underwent
nonelective cesarean section, while 22 had elective cesarean delivery. As for
NSVD deliveries, only one parturient received combined spinal and epidural
anesthesia (CSE) for labor. Neuraxial (n = 22 for spinal and n = 1 for CSE) and
general anesthesia (n = 4) rates for CSs were 85% and 15%, respectively.
Approximately 96% of neuraxial anesthesia choices were spinal anesthesia. Nearly
18.5% of CSs were not elective. Adverse outcomes included 2 preterm births, 2
preterm labors, 2 newborns with hepatitis, and one perinatal fetal death.
CONCLUSION: Parturients with ICP who had normal coagulation parameters despite
increased liver enzymes preoperatively underwent cesarean delivery under spinal
anesthesia without complication. Although maternal outcomes were generally
positive, adverse fetal and neonatal outcomes are more likely to occur,
particularly in cases with severe ICP.
PMID- 28425251
TI - Evaluation of plantar pressure distributions in patients with anteriorcruciate
ligament deficiency: preoperative and postoperative changes.
AB - BACKGROUND/AIM: Anterior cruciate ligament (ACL) deficiency results in several
kinematic changes in the lower extremities. The aim of this study is to define
the plantar pressure parameters in ACL-deficient patients and to show the effect
of ACL reconstruction on dynamic plantar pressure. MATERIALS AND METHODS: Forty
patients with unilateral ACL rupture and 40 healthy controls were included in
this study. Dynamic plantar pressures of both groups were recorded by the EMED SF
2 system during level walking. Thirteen of the patients who had ACL
reconstructions with hamstring autografts (HS group) were reevaluated at an
average of 14.5 months following the ACL reconstructions. RESULTS: ACL-deficient
patients had significantly lower hindfoot (P = 0.007) but higher midfoot pressure
values (P = 0.03) on their ipsilateral foot compared to control group subjects.
Ipsilateral hindfoot pressures were also found to be significantly lower than
those of the contralateral foot (P = 0.001). Hindfoot pressure values of the HS
group were increased in postoperative measurements (P = 0.01). CONCLUSION: ACL
deficient patients have altered plantar pressure distributions and ACL
reconstructions restore these changes to normal. Pedobarography might be used as
a practical method for dynamic functional assessment of ACL-deficient patients.
PMID- 28425252
TI - Allergic and autoimmune disorders in families with selective IgA deficiency.
AB - BACKGROUND/AIM: IgA deficiency is the most common human primary immunodeficiency.
The prevalence of allergic disorders and autoimmunity is thought to be increased
in selective IgA deficiency (sIgAD). However, it is currently unclear if these
disorders coincide within these families. We aimed to evaluate the frequency of
allergic and autoimmune disorders in children with sIgAD and their first-degree
relatives (FDRs). MATERIALS AND METHODS: The study included 81 children diagnosed
with sIgAD and 274 of their FDRs. The presence of allergic and autoimmune
disorders was evaluated and serum antithyroglobulin and antithyroid peroxidase
levels were measured in both patients and their first-degree relatives. RESULTS:
The mean age of the patients was 9.9 +/- 3.9 years. Among the patients with
sIgAD, 45.7% of them had at least one allergic disorder and 17.3% of them had at
least one autoimmune disorder. The frequencies of asthma, allergic rhinitis, and
eczema in the FDRs of sIgAD patients were 10.9%, 9.1%, and 7.7%, respectively.
Among their FDRs, 14.6% had autoimmunity, compared to an estimate of 5% in the
general population. CONCLUSION: Increased frequency of allergic and autoimmune
disorders in patients with sIgAD and their FDRs suggests a possible common
predisposing genetic component for sIgAD and autoimmunity in these families.
PMID- 28425253
TI - Association of the CETP gene TaqIB and D442G polymorphisms with essential
hypertension in the Chinese Mongolian population.
AB - BACKGROUND/AIM: This study aimed to explore the associations of the cholesteryl
ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential
hypertension (EH). MATERIALS AND METHODS: In this case-control study, 883
hypertensive patients and 1044 normal controls were randomly selected from the
Mongolian population of China. Polymerase chain reaction (PCR) and direct
sequencing of PCR products were used to identify the genotypes. Haplotype
analysis was performed by estimating the haplotype frequencies using the online
SHEsis package. RESULTS: The distribution frequency of the B2-G haplotype was
significantly lower in the EH group than in the control group (0.7% vs. 1.9%, P =
0.001, OR = 0.359 [0.188-0.689]). Subjects with the B2B2 genotype showed
significantly lower levels of total cholesterol (TC) (P < 0.05). When subgrouped
by sex, male subjects with the B2B2 genotype showed significantly increased high
density lipoprotein cholesterol and decreased TC levels (P < 0.05), and those
with the B2 allele showed significantly lower triglyceride levels as compared to
the subjects with the B1B1 homozygote (P < 0.05). CONCLUSION: TaqIB and D442G
polymorphisms of the CETP gene did not independently affect the risk of
developing EH in the Chinese Mongolian population, while the B2-G haplotype
obviously decreased the susceptibility to EH. The B2 allele could alter the blood
lipid level and reduce the risk of developing cardiovascular diseases.
PMID- 28425254
TI - Wheezing, asthma, and atopy in premature infants at 2 years of age.
AB - BACKGROUND/AIM: We aimed to evaluate wheezing, bronchial asthma (BA), and atopy
in premature infants at 2 years of age via a cross-sectional study. MATERIALS AND
METHODS: Premature infants at <37 weeks of gestational age (GA) were assessed for
atopy by skin-prick test and serum immunoglobulin E level at 2 years of age. The
family's and infant's histories of allergy, BA, atopy, and wheezing were obtained
by questionnaire and from hospital records. RESULTS: There were 98 infants, with
mean birth weight (BW) 1517.4 +/- 486.5 g and GA 30.8 +/- 2.9 weeks. The
frequencies of wheezing, asthma, and bronchopulmonary dysplasia (BPD) were 32.7%,
16.3%, and 14.3%, respectively. Skin-prick tests were positive for 11 subjects,
with allergy to cereals for 7 infants, egg for 3, and peanut for 1. Wheezing was
related to GA, BW, respiratory distress syndrome, mechanical ventilation, sepsis,
asphyxia, smoking, antenatal steroid, BA, palivizumab prophylaxis, number of
people in the household, and duration of hospitalization (P < 0.05). Wheezing was
negatively correlated to GA. Family history of BA, smoking, and number of people
in the household were linked to BA (P < 0.05). CONCLUSION: Wheezing was related
to degree of premature birth, but BA was linked to BA in the family and smoking.
Increased gestation should improve the infant's respiratory health up to 2 years
of age.
PMID- 28425255
TI - Aortic valve sclerosis is associated with the extent of coronaryartery disease in
stable coronary artery disease.
AB - BACKGROUND/AIM: Aortic valve sclerosis (AVS) is characterized by lipid deposition
and calcific infiltration on the edge of aortic leaflets without significant
restriction of motion. The SYNTAX Score (SS) is an important method for
evaluating coronary artery disease (CAD). Many studies showed that there is an
important relation between the SS and undesired cardiac outcomes. In our study,
we investigated the correlation between the SS and AVS by including both ACS and
stable CAD cases. MATERIALS AND METHODS: We enrolled 543 patients with CAD who
underwent coronary angiography into this cross-sectional study between September
2013 and September 2014. RESULTS: The study population was divided into two
groups according to SS values above and below 22. Diabetes mellitus (DM)
incidence was greater in the group with high SS values (26.3% vs. 19.2%, P =
0.052.). Left ventricular ejection fraction (LVEF) and glomerular filtration rate
were lower. Low-density lipoprotein cholesterol and triglyceride levels were
lower while platelet counts were higher. In multivariate analysis, for the stable
coronary artery group AVS existence, platelet count, LVEF value, and chronic
obstructive pulmonary disease were found as independent predictors. CONCLUSION:
Our study results demonstrated that AVS is significantly associated with the
complexity of CAD, especially in patients with stable CAD. This study provides
new information regarding the role of AVS in CAD complexity.
PMID- 28425256
TI - Predictive values of plasma KL-6 in bronchopulmonary dysplasia in preterm
infants.
AB - BACKGROUND/AIM: It has been suggested that plasma KL-6 increases in premature
infants with bronchopulmonary dysplasia (BPD). We aimed to evaluate the
predictive values of KL-6 in BPD. MATERIALS AND METHODS: The study was performed
in preterm neonates with birthweight <=1500 g and gestational age <=32 weeks.
Plasma KL-6 levels were measured on postnatal days 1, 7, and 14. RESULTS: BPD was
identified in eight of the 28 study infants. On postnatal days 1 and 7, plasma KL
6 levels were similar in infants with BPD [on day 1: 8.9 (7.5-17.8) U/mL and on
day 7: 16.8 (10.5-47.7) U/mL] and without BPD [on day 1: 10.8 (9.4-17.2) U/mL and
on day 7: 12.9 (5.8-19.3) U/mL] (P = 0.38 and P = 0.13, respectively). On day 14,
KL-6 levels were significantly higher in infants with BPD [155.2 (15.3-545.6)
U/mL] than they were in infants without BPD [7.9 (7.7-15.6) U/mL] (P = 0.001).
The best predictor was KL-6 levels on postnatal day 14 (area under the ROC curve
= 0.88; range 0.75-1.0; P = 0.002). At this point, KL-6 level of 59.7 U/mL showed
a specificity of 90.0% and negative predictive value of 85.7% for BPD.
CONCLUSION: High plasma KL-6 levels on postnatal day 14 in premature infants may
predict the development of BPD.
PMID- 28425257
TI - Role of hygienic factors in the etiology of allergic disorders in children.
AB - BACKGROUND/AIM: We investigated the role of body flora and chronic inflammatory
infections in the etiology of allergic disorders in Turkish children. MATERIALS
AND METHODS: Forty pediatric asthma patients with positive skin prick tests and
40 age-matched healthy subjects with negative skin prick tests were enrolled in
this cross-sectional study. Serum H. pylori IgG, viral hepatitis serology, IL-10,
and TGF-beta levels were measured. Stool and throat cultures were taken and
tested for occurrence of microorganisms. RESULTS: A significantly higher
percentage of nonatopic subjects tested positive for anti-H. pylori antibodies
compared to atopic subjects (60% vs. 20%). Serum IL-10 levels were also
significantly higher in nonatopic subjects. No significant differences in direct
microscopy and culture specimens of stools were observed. Examination of throat
flora showed significantly higher occurrences of Neisseria and beta-hemolytic
Streptococcus in nonatopic subjects, but higher occurrences of gram-positive
bacilli in atopic subjects. CONCLUSION: Higher prevalence of anti-H. pylori
antibody and higher serum levels of IL-10 in nonatopic subjects suggest that
chronic infection and inflammation may protect against atopic disease. Higher
occurrences of Neisseria and beta-hemolytic Streptococcus in throat cultures from
nonatopic subjects are novel findings that lend further support to the hygiene
hypothesis.
PMID- 28425258
TI - Assessment of developmental and radiological long-term outcomeof children with
surgically treated midgut volvulus.
AB - BACKGROUND/AIM: The aim is to evaluate the long-term outcome of asymptomatic
patients who underwent surgical correction for midgut volvulus. MATERIALS AND
METHODS: Seven patients managed surgically for midgut volvulus in the last 3
years were included. Demographic features, symptoms at presentation, diagnoses,
surgical procedures, and complications were recorded. Patients were then
contacted for follow-up and evaluation of long-term outcomes. General physical
conditions, anthropometric parameters, feeding habits, and defecation histories
were evaluated. Laboratory examinations were performed. Color Doppler
ultrasonography (CDUS) was performed to evaluate blood flow in the superior
mesenteric artery (SMA). RESULTS: In total, seven patients were identified. The
median age at admission was 3 days (0-90 days). Mean age at follow-up was 17 +/-
2 months. Growth parameters were normal in all cases. Four patients had low
levels of ferritin and transferrin saturation. One patient had microcytic anemia.
Another patient had low serum zinc level. One patient who had ileal resection had
a high level of steatorrhea in stool examination. In CDUS, SMA blood flow volume
was low in all cases. Peak-systolic velocity and resistance index were low in all
but one case. CONCLUSION: Despite uneventful postoperative courses, all patients
operated on for midgut volvulus showed mild laboratory changes and decreased
blood flow in the SMA in long-term follow-up.
PMID- 28425260
TI - The efficacy of microphototherapy with a MedLight CupCUBEGrimed device in
psoriatic patients with localized lesions.
AB - BACKGROUND/AIM: Psoriasis is a chronic skin disease. To reduce side effects
associated with current treatment modalities, new treatment methods are required.
Some clinicians have begun to use microphototherapy to treat psoriatic patients
with a limited number of lesions (lesions affecting <10% of the body surface
area). MATERIALS AND METHODS: Microphototherapy is indicated in patients whose
lesions persist despite systemic and topical treatment or when such treatment is
contraindicated. Our study aimed to evaluate the efficacy of microphototherapy in
psoriasis patients with localized lesions. Patients in this unblinded and
prospective study were treated three times a week for 50 sessions using a
MedLight CupCUBE Grimed microphototherapy device that emits an ultraviolet B
(UVB) spectrum. RESULTS: Forty-five lesions in 23 psoriatic patients were
treated. Treatment outcome was evaluated based on the Psoriasis Severity Index
(PSI). PSI scores decreased significantly during the treatment. CONCLUSION: The
MedLight CupCUBE Grimed microphototherapy device was effective for the treatment
of psoriasis patients with localized lesions. The device can administer UVB
radiation to involved regions while protecting uninvolved regions and minimizing
radiation dose. However, having to be administered by experienced technicians and
the long time required for each treatment session are disadvantages of the
technique.
PMID- 28425259
TI - Analysis of FANCC gene mutations (IVS4+4A>T, del322G, and R548X)in patients with
Fanconi anemia in Pakistan.
AB - BACKGROUND/AIM: Fanconi anemia (FA) is an autosomal recessive disease determined
by mutations in at least 16 genes, with distinct distributions in different
populations. To the best of our knowledge, there are no reports regarding the
molecular basis of the disease in FA patients in Pakistan. The current study
aimed to determine the frequency of FANCC gene mutations, i.e. IVS4+4A>T,
del322G, and R548X, in FA patients. MATERIALS AND METHODS: Genomic DNA was
obtained from 36 FA patients. All samples were analyzed by polymerase chain
reaction and restriction fragment length polymorphism techniques. RESULTS:
Mutation IVS4+4A>T was identified in 26 (72.2%) patients. It was homozygous in 6
and heterozygous in 20 patients. Del322G and R548X were found with the following
prevalences: del322G, 5.6%, and R548X, 5.6%. Patients with these two mutations
were compound heterozygotes having concomitant IVS4+4A>T mutation. CONCLUSION:
These results suggest that mutation IVS4+4A>T is the most prevalent mutation in
our group of patients. This analysis of Pakistani patients also suggests that
there is no significant difference between IVS4+4A>T homozygotes and the rest of
the patients with regard to severity of clinical phenotype.
PMID- 28425261
TI - Central line-associated blood stream infections: characteristics and risk factors
for mortality over a 5.5-year period.
AB - BACKGROUND/AIM: Central line-associated bloodstream infections (CLABSIs) are
associated with substantial morbidity and mortality and the infection rates vary
in a wide range1397645907(high: 62.5%; low: 20%) in developing countries. We
aimed to investigate the characteristics and the risk factors for mortality in
patients with CLABSIs in intensive care units (ICUs) and provide the relevant
data. MATERIALS AND METHODS: The electronic medical records database and file
records obtained through active surveillance by an infection control committee of
a hospital were screened to identify patients with CLABSIs hospitalized from
January 2008 through July 2013. RESULTS: A total of 166 CLABSI episodes in 158
patients out of 17,553 on 38,562 catheter and 94,512 hospitalization days were
evaluated. The infection developed in catheterized patients at a median of 14
days (range 2-88), and the highest infection rate with 13.4% (n = 20) was the
femoral region among the places where the catheter was inserted. Of the patients
catheterized, 54.4% survived whereas 45.6% died. In patients having Candida
infection, the mortality was significantly higher. High APACHE II scores and
Candida infections were found to be significant risk factors associated with
mortality. CONCLUSION: APACHE II scores and bloodstream infection with Candida
species were the most powerful predictors of mortality. In ICU practice, health
care givers must consider the emerging role of Candida for both invasiveness and
mortality.
PMID- 28425262
TI - Copeptin levels in carbon monoxide poisoning.
AB - BACKGROUND/AIM: The aim of this study is to identify the copeptin levels in
patients presenting with carbon monoxide (CO) poisoning to the emergency
department and to investigate its correlation with the neurological effects.
MATERIALS AND METHODS: The study group consisted of patients presenting with CO
poisoning and carboxyhemoglobin levels >10%. Blood samples for copeptin levels
were obtained twice, first at presentation then at the fourth hour of
observation. The data were analyzed using SPSS 16 for Windows. RESULTS: The
median copeptin levels of the patient group were identified as 0.63 (0.39-1.06)
ng/mL at hour 0 and 0.41 (0.31-0.49) at hour 4. The copeptin levels of the
control group were 0.34 (0.25-0.42) ng/mL and were significantly lower than those
of the patient group (P < 0.000). According to our results, 0.345 ng/mL for
plasma copeptin level as the best cut-off level may be used with sensitivity of
94.0% and specificity of 60%. The copeptin levels at hour 0 were statistically
significantly higher in the neurologically affected patients than those not
affected (P < 0.001). CONCLUSION: In this study it was shown that blood copeptin
levels increase in patients presenting to the emergency department with CO
poisoning.
PMID- 28425263
TI - Combination therapy with dendritic cell-based vaccine and anti-CD69 antibody
enhances antitumor efficacy in renal cell carcinoma-bearing mice.
AB - BACKGROUND/AIM: Dendritic cell-based vaccine therapy for renal cell carcinoma is
effective but requires improvement. Here we explored whether combination therapy
with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor
efficacy in renal cell carcinoma-bearing mice. MATERIALS AND METHODS: Balb/c mice
were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On
day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated
or were treated with Renca tumor lysate-pulsed dendritic cells (i.e. dendritic
cell-based vaccine), anti-CD69 antibody, or a combination of Renca tumor lysate
pulsed dendritic cells with anti-CD69 antibody. The mice were sacrificed on day
28. Tumor volume was measured for analysis of antitumor efficacy. Spleens were
excised to evaluate antitumor immunological responses by measuring the
proliferation and activation of T cells, which have the capacity to recognize and
destroy tumor cells. RESULTS: Combination treatment with Renca tumor lysate
pulsed dendritic cells and anti-CD69 antibody resulted in significant decreases
in tumor volume and significant increases in T-cell proliferation and activity,
compared with no treatment or either treatment alone. CONCLUSION: These findings
indicate that anti-CD69 antibody can potentiate antitumor efficacy of dendritic
cell-based vaccine. The augmented therapeutic efficacy conferred by the
combination therapy may be associated with increased T-cell proliferation and
activity.
PMID- 28425264
TI - Rho/rho-kinase signalling in chronically alcohol-fed mice.
AB - BACKGROUND/AIM: The effects of chronic ethanol consumption on male sexual
function are debateable, and its effects on the Rho/Rho-kinase pathway are
unknown. Therefore, we investigated smooth muscle reactivity and Rho/Rho-kinase
signalling in the corpus cavernosum of ethanol-fed mice. MATERIALS AND METHODS:
Ethanol was added to drinking water at 5% concentration in the first 2 days with
5% increment every subsequent 2 days, up to a final concentration of 20% for 45
days. Corpora cavernosa were isolated and a cumulative dose-response curve to
phenylephrine was obtained. Acetylcholine (10-6 M), electrical field stimulation
(EFS, 40 V, 8-16 Hz) and Y-27632 (10-6-10-5 M)-induced relaxations were compared
in the control and ethanol groups. RESULTS: Blood ethanol levels in the control
and ethanol-treated mice were 1.5 +/- 0.3 mg/dL and 37.4 +/- 4.1 mg/dL (P <
0.001), respectively. Phenylephrine-induced contractile responses were
potentiated in the ethanol group, with pD2 values of 4.92 +/- 0.18 and 5.71 +/-
0.21 (P < 0.01) in the corpus cavernosum obtained from control and alcohol-fed
mice, respectively. The relaxant responses to acetylcholine and EFS, but not Y
27632, were significantly augmented in the corpus cavernosum obtained from
ethanol-treated mice. However, expression and activation of Rho-kinase remained
unchanged in the alcohol group. CONCLUSION: Ethanol drinking may increase
sensitivity to both vasoconstrictors and vasodilators in the mouse corpus
cavernosum without any alteration in Rho/Rho-kinase signalling.
PMID- 28425265
TI - Effects of Ankaferd BloodStopper on dermal healing in diabetic rats.
AB - BACKGROUND/AIM: Diabetes mellitus inhibits wound-induced angiogenesis, impairs
the wound healing process, and leads to the development of chronic wounds.
Ankaferd BloodStopper (ABS) is a new and promising local haemostatic agent.
Although the mechanism of ABS-mediated haemostasis is well established, little is
known about the associated histological and biochemical tissue reactions. The aim
of this study was to evaluate the effects of this new-generation local
haemostatic agent on short-term soft-tissue healing in streptozotocin (STZ)
treated rats. MATERIALS AND METHODS: The 24 Wistar albino rats used in this study
were divided into STZ-treated (STZ, n = 12) and nontreated groups (control, n =
12). Four days prior to surgery, rats in the STZ group were subcutaneously
administered 60 mg/kg STZ intraperitoneally, while rats in the control group were
administered 1 mL saline/kg. An incision was made in the dorsal dermal tissue of
all rats, and either ABS or no haemostatic agent (NHAA) was applied to the wound
before suturing. All of the rats were euthanised on postoperative day 4. Blood
and skin samples were evaluated biochemically and histologically. RESULTS: The
results showed that STZ treatment impaired soft-tissue healing, assessed by
measuring glutathione and lipid peroxidation levels. Moreover, while good
histological results were obtained in the control group treated with ABS, there
were fewer benefits in the STZ-treated group. CONCLUSION: ABS's benefits in the
control group seemed to lose their effectiveness under STZ medication.
PMID- 28425266
TI - Nitroglycerin challenge induces lateralized headache in nasociliarynerve-ligated
rats: implications for chronic migraine.
AB - BACKGROUND/AIM: Chronic migraine is a common debilitating disease with limited
treatment options. We aimed to develop a novel model for chronic migraine by
ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to
exacerbate acute headache attacks. MATERIALS AND METHODS: Exacerbation of the
headache was induced by NTG (10 mg/kg, subcutaneously) administered to male
Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold
allodynia was tested using Von Frey (VF) filaments and acetone, respectively.
Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were
investigated. RESULTS: NTG administration significantly decreased VF threshold
values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw
(P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P
= 0.013). The number/rate of entrance to open arms in the EPM was significantly
decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry
disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem
TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 +/- 4.7,
contralateral 11.8 +/- 1.9, P < 0.05) in chronic NCN-ligated rats exposed to
acute NTG. CONCLUSION: The presented model provides a valid chronic migraine
model relevant to humans, as NTG challenge in chronic NCL rats generated
lateralized headache with cephalic and extracephalic allodynia, altered cold
sensitivity, anxiety, and neuronal activation in the nociceptive laminae of
brainstem trigeminal pain nuclei.
PMID- 28425267
TI - Modifications of mice gut microflora following oral consumption ofLactobacillus
acidophilus and Bifidobacterium bifidum probiotics.
AB - BACKGROUND/AIM: Thirty male BALB/c mice were equally divided into three groups:
control, L. acidophilus, and B. bifidum for the assessment of the probiotics'
stability in the gut microflora. MATERIALS AND METHODS: First, the gut microflora
of the mice was checked every 3 days (days 3, 6, 9, and 12) without probiotic
consumption, and then the mice were daily given orally 1.5 g of probiotics in 30
cc of drinking water. The consumption of probiotics was then stopped for recovery
and then the consumption continued for 5 months. RESULTS: On day 9 after the
consumption of the probiotics, L. acidophilus and B. bifidum were significantly
increased from 4% to 83% and from 1% to 61%, respectively. L. acidophilus count
showed no significant decrease at the end of 5 months compared to day 9 of
probiotic consumption (74%), but B. bifidum count was dramatically decreased to
45% and 36% at the end of 1 and 5 months, respectively. CONCLUSION: Our results
revealed that, unlike B. bifidum, the amount of L. acidophilus remained almost
unchanged in the long term, indicating more stability of L. acidophilus than B.
bifidum in the gut microflora.
PMID- 28425268
TI - Efficient production of nanobodies against urease activity ofHelicobacter pylori
in Pichia pastoris.
AB - BACKGROUND/AIM: Helicobacter pylori is a major health problem. One of the
therapeutic approaches is administration of antibody against H. pylori. The
methylotrophic Pichia pastoris is a suitable host for expression of recombinant
antibody fragments. The aims of this study were the expression and the evaluation
of camelid nanobody in the yeast Pichia pastoris. MATERIALS AND METHODS: The
camelid-derived heavy-chain antibody (nanobody) against the UreC subunit of
urease from H. pylori was subcloned in the pPink-HC shuttle vector and
transferred into Escherichia coli TOP10. After digestion and purification, the
shuttle vector was transformed in the PichiaPink expression system. The
expression was evaluated in an in vitro system. RESULTS: The yield of the
nanobody expressed in P. pastoris was estimated to be 5 mg/L as compared to 2
mg/L expressed by E. coli. The nanobody was purified and binding affinity to the
UreC antigen was evaluated using ELISA. Neutralization abilities of the two
nanobodies expressed in yeast and E. coli were compared. The yeast-expressed
nanobody specifically detected recombinant UreC and inhibited urease activity
with high efficiency. CONCLUSION: The results suggest attribution of the enhanced
quality and quantity of the nanobody produced in P. pastoris to better
posttranslational modification and folding in the yeast cell.
PMID- 28425269
TI - Evaluation of cytotoxic, membrane, and DNA damaging effects of Thymus revolutus
Celak essential oil on different cancer cells.
AB - BACKGROUND/AIM: In this study, we evaluated Thymus revolutus Celak essential oil
and its two main constituents, gamma-terpinene and p-cymene, as potential
oxidative agents against lung cancer and epidermoid carcinoma cells. MATERIALS
AND METHODS: Cell viability assessment was made by CellTiter-Blue1397904493 cell
viability and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay after treatment with 5-600 MUg/mL concentrations of essential oil, gamma
terpinene, and p-cymene. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels
in parental H1299, epirubicin-resistant (drug-resistant) H1299, A549, and A431
cells were also assayed after essential oil, gamma-terpinene, and p-cymene had
been administered for 24 h. Glutathione S-transferase (GST), glutathione
peroxidase (GPx), glutathione reductase (GRx), and glucose 6-phosphate
dehydrogenase (G6PD) activities were determined. RESULTS: Parental H1299 cells
were found to be more sensitive to the cytotoxic effects of all compounds. While
A431 cells had the highest membrane damage, which was caused by essential oil
(IC50 and IC70), A549 cells had the highest DNA damage at IC50 and IC70 p-cymene
concentrations. G6PD, GST, GRx, and GPx enzyme activities of cells, which
increased against these compounds, depended on concentrations, incubation times,
and antioxidant capacities of the cells. CONCLUSION: This study suggests that
different cancer cells showed different cellular responses against potential
antitumor and prooxidative effects of the essential oil and its two main
constituents.
PMID- 28425270
TI - A new angiogenesis prognostic index with VEGFA, PlGF, and angiopoietin1 predicts
survival in patients with advanced gastric cancer.
AB - BACKGROUND/AIM: The role of angiogenic factors in gastric cancer is not clear. We
aimed to assess the role of vascular endothelial growth factor A (VEGFA),
angiopoietin 1 (Ang-1), and placental growth factor (PlGF) in the prognosis of
patients with advanced gastric cancer. MATERIALS AND METHODS: Thirty consecutive
patients treated with a modified DCF (docetaxel, cisplatin, and fluorouracil)
regimen were included in the study. The plasma VEGFA, Ang-1, and PlGF levels of
the patients before treatment and following two cycles of chemotherapy were
measured and evaluated as prognostic factors. RESULTS: Poor performance status
and lower Ang-1 levels were correlated with poor overall survival (OS). No
significant correlation between VEGFA or PlGF and OS was found. An angiogenesis
prognostic index (API) based on the levels of VEGFA, Ang-1, and PlGF was found to
be highly correlated with OS. Performance status and API were found as
independent prognostic factors for OS. Furthermore, a decrease in VEGFA by 25%
from the pretreatment level was also found as a prognostic factor for OS
independent of response to DCF regimen. CONCLUSION: Our results support the use
of the new API including VEGFA, Ang-1, and PlGF levels in patients with advanced
gastric cancer as a predictor of survival.
PMID- 28425271
TI - Molecular characteristics and antibiotic resistance of Acinetobacter
baumanniibeta-lactamase-producing isolates, a predominance of intrinsic blaOXA
51, and detection of TEM and CTX-M genes.
AB - BACKGROUND/AIM: The aim of this study was to determine the molecular
characteristics and antibiotic resistance of 13 (10 inpatient and three
outpatient) Acinetobacter baumannii beta-lactamase-producing isolates collected
in Bosnia and Herzegovina between December 2009 and May 2010. MATERIALS AND
METHODS: Susceptibility testing was performed by disk diffusion and broth
microdilution methods. The modified Hodge and combined disk test with
EDTA/phenylboronic acid was used to screen for carbapenemase production.
Production of extended spectrum beta-lactamases (ESBLs) was determined by double
disk synergy test. PCR was used to detect blaESBL/blacarb genes. RESULTS: Ten
(22.2%) inpatient and three (13.6%) outpatient isolates produced beta-lactamases,
ESBLs, or oxacillinases. More than 50% of the isolates showed multidrug
resistance. Resistance rates to gentamicin and ciprofloxacin of the inpatients
and outpatients were 80.0%, 60.0%, 75.0%, and 25.0%, respectively. MICs of
carbapenems for resistant isolates ranged from 32 to >256 MUg/mL. All imipenem
resistant Acinetobacter baumannii strains contained blaOXA-51. Three of the 10
inpatient isolates and one outpatient isolate containing blaOXA-51 additionally
produced other beta-lactamases (TEM/CTX-M/OXA-1). None of the inpatient or
outpatient isolates were positive for other carbapenemases, especially acquired
oxacillinases (blaOXA-23/blaOXA-24/blaOXA-58/blaOXA-143). CONCLUSION: Production
of blaOXA-51 presents an emerging threat in imipenem-resistant Acinetobacter spp.
from Bosnia and Herzegovina.
PMID- 28425272
TI - Effect of transfusion of washed red blood cells on serumpotassium level in
hemodialysis patients.
AB - BACKGROUND/AIM: This study aimed to compare washed red blood cell (WRBC)
transfusion versus nonwashed RBC (NWRBC) transfusion in terms of posttransfusion
potassium levels in dialysis patients on a day when the patient did not receive
dialysis. MATERIALS AND METHODS: The patients were randomly assigned into two
groups, i.e. those receiving WRBCs (n = 21) and those receiving NWRBCs (n = 17).
Both groups received one unit of RBCs. Serum potassium and sodium levels were
measured before and at the 1st, 2nd, 3rd, 4th, and 6th hours after transfusion.
RESULTS: In the WRBC group, the changes in the serum potassium levels at the 3rd,
4th, and 6th hours after transfusion were significant compared with
pretransfusion levels. In the serum potassium levels mean decreases by 0.38 +/-
0.57 mEq/L at the 3rd hour (P = 0.006), by 0.32 +/- 0.47 mEq/L at the 4th hour (P
= 0.005), and by 0.32 +/- 0.51 mEq/L at the 6th hour (P = 0.009) after
transfusion were significant compared with the pretransfusion levels. CONCLUSION:
Although nonwashed RBC transfusion does not change serum potassium levels, washed
RBC transfusion significantly reduces serum potassium levels. Washed RBC
transfusion is considered to be safer in hemodialysis patients with hyperkalemia
and anemia.
PMID- 28425273
TI - Radiation therapy for biliary tract tumors: the joint experience of three
centers.
AB - BACKGROUND/AIM: This study presents the joint experience of three centers in the
treatment of patients with biliary tract tumors with radiation therapy (RT).
MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed.
All of the patients who had undergone surgical resection received postoperative
adjuvant RT, whereas all of the patients who had not undergone a surgical
resection received RT with palliative intent. Twenty patients with adequate
performance status were treated with RT and chemotherapy, while the remaining
seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44
months. Local control was not achieved in 10 out of 11 patients who had received
RT with palliative intent. Systemic failure was observed in eight patients at 5
to 16 months. Fifteen patients died due to disease-related causes at 1 to 22
months. At 2 years, overall survival was 33% and disease-free survival was 19%. A
surgical resection with curative intent predicted improved local failure-free
survival and improved disease-free survival. CONCLUSION: Since local recurrence
is still the leading cause of failure following postoperative RT and the outcome
following palliative RT is far from satisfactory, the indications, the target
volume, and the doses for RT should be reconsidered.
PMID- 28425274
TI - Profile of POT1 as telomerase shelterin component discriminatesbetween cervical
cancer and normal cervical cells.
AB - BACKGROUND/AIM: Telomerase activity is influenced by hTERT transcriptional
regulation, shelterin, and posttranscriptional alternative splicing. Telomerase
shelterin such as POT1 is highly correlated with various cancers. However, the
profile of POT1 in cervical cancer has not been clearly identified. Therefore, it
is important to identify its profile in cervical cancer biopsy tissue and normal
cervical smears. MATERIALS AND METHODS: Biopsy tissue of cervical cancer patients
and normal cervical smears were characterized using SDS-PAGE and western blot.
Sixteen biopsy tissues of cervical cancer patients and 15 normal cervical smears
were measured for POT1 level using ELISA. RESULTS: The inline band at 70 kDa
indicated that all samples had protein that was identified as POT1. Western blot
showed that telomerase antibody only recognized POT1 in biopsy tissue of cervical
cancer patients. There was a significant difference (P = 0.01) in POT1 level
between biopsy tissue of cervical cancer patients and normal cervical smears.
CONCLUSION: POT1 was identified at 70 kDa in biopsy tissue of cervical cancer
patients and its level was higher than that in normal cervical smears. The high
level of POT1 in the biopsy tissue of cervical cancer patients showed the
influence of this shelterin component in cervical carcinogenesis and also cell
immortalization.
PMID- 28425275
TI - Associations between obesity and the radiographic phenotype in knee
osteoarthritis.
AB - BACKGROUND/AIM: Investigation of the association between obesity and the
distinction of radiographic patterns in knee osteoarthritis. MATERIALS AND
METHODS: Seven hundred and thirty-four women underwent weight-bearing antero
posterior knee radiography. Osteophytes and joint space narrowing (JSN) were
graded according to the OARSI atlas. Each subject was assigned to one of the
following groups with respect to the maximum score: osteophyte-dominant,
indeterminate, JSN-dominant, and radiographically normal. RESULTS: Obese patients
had a significantly more frequent osteophyte-dominant pattern compared to
nonobese subjects (74.5% and 38%, respectively, P < 0.001). Logistic regression
analysis demonstrated that obesity had a stronger association with an osteophyte
dominant pattern compared to a JSN-dominant pattern (OR and 95% CI = 7.16 (3.15
16.26) and 1.63 (0.96-2.78), respectively). Age had a very weak effect on the
distinction to an osteophyte-dominant pattern and no effect on JSN dominance (OR
and 95% CI = 1.1 (1.06-1.15) and 1.02 (0.99-1.05), respectively). CONCLUSION:
There might be an association between obesity and the radiographic phenotype in
patients with knee osteoarthritis. The findings suggest that the association
between obesity and the osteophyte formation is stronger than that of JSN.
PMID- 28425276
TI - Bezlotoxumab and Recurrent Clostridium difficile Infection.
PMID- 28425277
TI - "Zombie" Outbreak Caused by Synthetic Cannabinoid.
PMID- 28425278
TI - Screening for Colorectal Neoplasia.
PMID- 28425279
TI - Screening for Colorectal Neoplasia.
PMID- 28425280
TI - Large-Scale Synthesis of Monodisperse UiO-66 Crystals with Tunable Sizes and
Missing Linker Defects via Acid/Base Co-Modulation.
AB - Beyond their pore structures and surface chemistry, precise controls over other
attributes of metal-organic frameworks (MOFs) such as shapes, sizes, and defects
are also favorable to their fundamental studies and applications but still remain
challenging. Herein, we reported an acid/base co-modulation strategy to the large
scale synthesis of monodisperse UiO-66 crystals with acetic acid for modulating
crystal shape and with triethylamine (TEA) as a base for controlling the
nucleation of crystallization and tuning the formation of missing linker defects
via promoting presumably the singe deprotonation of terephthalic acid linkers.
The obtained monodisperse MOF crystals have a well-defined octahedral shape,
tunable sizes ranging from ~500 nm to ~2 MUm, and high thermal stability. Their
assembled-monolayers are responsive to methanol vapor with the crystal size
dependent and defect-relevant sensing performances.
PMID- 28425281
TI - Hybridized C-O-Si Interface States at the Origin of Efficiency Improvement in
CNT/Si Solar Cells.
AB - Despite the astonishing values of the power conversion efficiency reached, in
just less than a decade, by the carbon nanotube/silicon (CNT/Si) solar cells,
many doubts remain on the underlying transport mechanisms across the CNT/Si
heterojunction. Here, by combining transient optical spectroscopy in the
femtosecond timescale, X-ray photoemission, and a systematic tracking of I-V
curves across all phases of the interlayer SiOx growth at the interface, we grasp
the mechanism that adequately preserves charge separation at the junction,
hindering the photoexcited carrier recombination. Moreover, supported by ab
initio calculations aimed to model the complex CNT-Si heterointerface, we show
that oxygen-related states at the interface act as entrapping centers for the
photoexcited electrons, thus preventing recombination with holes that can flow
from Si to CNT across the SiOx layer.
PMID- 28425282
TI - Mechanical Force Sensitive Acrylic Latex Coating.
AB - We prepared force sensitive acrylic latex coatings by covalently incorporating
spiropyran mechanophore. The acrylic latexes were obtained through emulsion
copolymerization of butyl acrylate (BA), methyl methacrylate (MMA) with
vinyltriethoxysilane (VTES) as interparticle cross-linker, and (1'-(2
(methacryloyloxy)ethyl)-3',3'-dimethylspiro[chromene-2,2'-indolin]-6-yl)methyl
methacrylate) (SP) as intraparticle cross-linker. The latexes of P(BA-co-MMA-co
SP-co-VTES) were subsequently cast onto Teflon-coated surface to form latex
coatings. The condensation of hydrolyzed VTES provided interparticle cross
linking and improved mechanical properties of the formed thin films.
Intraparticle cross-linker SP endowed the coatings with mechanoreponsiveness. The
mechanoactivation of SP-containing latex films was demonstrated. Increasing the
content of intra-cross-linker SP resulted in higher stress sensitivity and lower
critical stress required for mechanoactivation. Increasing the content of
interparticle cross-linker VTES resulted in higher critical stress for SP
mechanoactivation but had little effect on the stress sensitivity. Tg and
operation temperature also showed significant effect on mechanoactivation. Slower
strain rate allowed for higher SP-to-MC conversion. This work represents the
first example of mechanochromic acrylic latexes and provides insight into the
design of force sensitive and self-reporting polymer coatings.
PMID- 28425283
TI - Total Synthesis of (-)-Angiopterlactone B.
AB - An enantioselective total synthesis of (-)-angiopterlactone B has been
accomplished in four steps. The synthesis features a proposed biomimetic domino
ring-contraction/oxa-Michael/Michael dimerization sequence, forming three new
bonds, two new rings, and three new contiguous stereogenic centers in a single
step. It has been determined that the originally proposed absolute configuration
of natural (+)-angiopterlactone B needs revision. This reveals that
angiopteroside, a known glycoside natural product, is the likely biosynthetic
precursor to (+)-angiopterlactone B.
PMID- 28425284
TI - pH Triggered Size Increasing Gene Carrier for Efficient Tumor Accumulation and
Excellent Antitumor Effect.
AB - High efficiency and serum resistant capacity are important for gene carrier in
vivo usage. In this study, transfection efficiency and cell toxicity of
polyethylenimine (PEI) (branched, Mw = 25K) was remarkably improved, when mixed
with polyanion (polyethylene glycol-polyglutamic acid (PEG-PLG) or polyglutamic
acid (PLG)). Different composite orders of PEI, polyanion, and gene, for example,
PEI is first complexed with DNA, and then with polyanion, or PEI is first
complexed with polyanion, and then with DNA, were studied. Results showed that
only the polyanion/PEI complexes exhibited additional properties, such as
decreased pH, resulting in increased particle size, as well as enhanced serum
resistance capability and improved tumor accumulation. The prepared gene carrier
showed excellent antitumor effect, with no damage on major organs, which is
suitable for in vivo gene antitumor therapy.
PMID- 28425285
TI - Directed Evolution of Carbonyl Reductase from Rhodosporidium toruloides and Its
Application in Stereoselective Synthesis of tert-Butyl (3R,5S)-6-Chloro-3,5
dihydroxyhexanoate.
AB - tert-Butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate ((3R,5S)-CDHH) is a key
intermediate of atorvastatin and rosuvastatin synthesis. Carbonyl reductase
RtSCR9 from Rhodosporidium toruloides exhibited excellent activity toward tert
butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH). For the activity of
RtSCR9 to be improved, random mutagenesis and site-saturation mutagenesis were
performed. Three positive mutants were obtained (mut-Gln95Asp, mut-Ile144Lys, and
mut-Phe156Gln). These mutants exhibited 1.94-, 3.03-, and 1.61-fold and 1.93-,
3.15-, and 1.97-fold improvement in the specific activity and kcat/Km,
respectively. Asymmetric reduction of (S)-CHOH by mut-Ile144Lys coupled with
glucose dehydrogenase was conducted. The yield and enantiomeric excess of (3R,5S)
CDHH reached 98 and 99%, respectively, after 8 h bioconversion in a single batch
reaction with 1 M (S)-CHOH, and the space-time yield reached 542.83 mmol L-1 h-1
g-1 wet cell weight. This study presents a new carbonyl reductase for efficient
synthesis of (3R,5S)-CDHH.
PMID- 28425286
TI - Enantioselective Spirocyclopropanation of para-Quinone Methides Using Ammonium
Ylides.
AB - The use of Cinchona alkaloid-based chiral ammonium ylides allows for the first
highly enantioselective and broadly applicable spirocyclopropanation reactions of
para-quinone methides. This strategy provides a straightforward protocol toward
the chiral spiro[2.5]octa-4,7-dien-6-one skeleton, which is a frequently found
structural motif in important biologically active molecules.
PMID- 28425287
TI - Vertical Charge Transfer and Lateral Transport in Graphene/Germanium
Heterostructures.
AB - Heterostructures consisting of two-dimensional (2D) materials and conventional
semiconductors have attracted a lot of attention due to their application in
novel device concepts. In this work, we investigated the lateral transport
characteristics of graphene/germanium heterostructures and compared them with the
transport properties of graphene on SiO2. The heterostructures were fabricated by
transferring a single layer of graphene (Gr) onto a lightly doped germanium (Ge)
(100) substrate. The field-effect measurements revealed a shift in the Dirac
voltage of Gr on the Ge substrates compared to that of the Gr on SiO2. Transfer
length model measurements show a significant difference in the sheet resistance
of Gr on Ge compared to that of the Gr on SiO2. The results from the electrical
and structural characterization suggest that a charge transfer in the order of
1012 cm-2 occurs between Gr and Ge resulting in a doping effect in the graphene
sheet. A compact electrostatic model extracted the key electronic properties of
the Gr/Ge interface. This study provides valuable insights into the electronic
properties of Gr on Ge, which are vital to the development of novel devices based
on mixed 2D and 3D structures.
PMID- 28425288
TI - Tracking Nitrogen Sources, Transformation, and Transport at a Basin Scale with
Complex Plain River Networks.
AB - This research developed an innovative approach to reveal nitrogen sources,
transformation, and transport in large and complex river networks in the Taihu
Lake basin using measurement of dual stable isotopes of nitrate. The spatial
patterns of delta15N corresponded to the urbanization level, and the nitrogen
cycle was associated with the hydrological regime at the basin level. During the
high flow season of summer, nonpoint sources from fertilizer/soils and
atmospheric deposition constituted the highest proportion of the total nitrogen
load. The point sources from sewage/manure, with high ammonium concentrations and
high delta15N and delta18O contents in the form of nitrate, accounted for the
largest inputs among all sources during the low flow season of winter. Hot spot
areas with heavy point source pollution were identified, and the pollutant
transport routes were revealed. Nitrification occurred widely during the warm
seasons, with decreased delta18O values; whereas great potential for
denitrification existed during the low flow seasons of autumn and spring. The
study showed that point source reduction could have effects over the short-term;
however, long-term efforts to substantially control agriculture nonpoint sources
are essential to eutrophication alleviation for the receiving lake, which
clarifies the relationship between point and nonpoint source control.
PMID- 28425289
TI - Imaging Metastable States and Transitions in Proteins by Trajectory Map.
AB - It has been a long-standing and intriguing issue to develop robust methods to
identify metastable states and interstate transitions from simulations or
experimental data to understand the functional conformational changes of
proteins. It is usually hard to define the complicated boundaries of the states
in the conformational space using most of the existing methods, and they often
lead to parameter-sensitive results. Here, we present a new approach, visualized
Trajectory Map (vTM), to identify the metastable states and the rare interstate
transitions, by considering both the conformational similarity and the temporal
successiveness of conformations. The vTM is able to give a nonambiguous
description of slow dynamics. The case study of a beta-hairpin peptide shows that
the vTM can reveal the states and transitions from all-atom MD trajectory data
even when a single observable (i.e, one-dimensional reaction coordinate) is used.
We also use the vTM to refine the folding/unfolding mechanism of HP35 in explicit
water by analyzing a 125 MUs all-atom MD trajectory and obtain folding/unfolding
rates of about 1/MUs, which are in good agreement with the experimental values.
PMID- 28425290
TI - Bandgap Narrowing of Lead-Free Perovskite-Type Hybrids for Visible-Light
Absorbing Ferroelectric Semiconductors.
AB - Perovskite-type hybrids (e.g., CH3NH3PbI3) hold great promise in photovoltaics
and optoelectronics due to their remarkable semiconducting properties and
potential ferroelectricity. However, to date, conclusive evidence for the bulk
ferroelectricity of CH3NH3PbI3 is still lacking. In this context, it is highly
desirable to assemble concrete perovskite ferroelectric hybrids with the
semiconducting feature. Here we report, for the first time, a class of lead-free
perovskite halides, (N-methylpyrrolidinium)3Sb2Cl9-9xBr9x (x = 0-1), showing
large ferroelectric polarizations (5.2-7.6 MUC/cm2) and pronounced semiconducting
performances. In particular, a wide tunability of their optical bandgaps (3.31
2.76 eV) enables superior visible-light-induced photocurrents (~10 nA/cm2), which
allow for assembling of the crystal-based photodetectors. Our work paves a new
way to build environmentally benign optoelectronic devices based on low-bandgap
ferroelectric hybrids.
PMID- 28425291
TI - Dispersed Vanadium in Three-Dimensional Dendritic Mesoporous Silica Nanospheres:
Active and Stable Catalysts for the Oxidative Dehydrogenation of Propane in the
Presence of CO2.
AB - The uniform monodispersed vanadium-doped three-dimensional dendritic mesoporous
silica nanospheres (nV-MSNSs) were successfully synthesized in a heterogeneous
oil-water biphase stratification reaction system and characterized by several
state-of-the-art methods. The synthesized nV-MSNSs were applied to the oxidative
dehydrogenation of the propane (ODHP) reaction with the presence of CO2 and
exhibited excellent catalytic performances. The results show that the vanadium
loading (1.3-8.0 wt %) evidently influences the textural properties, oxidation
state, and polymerization degree of vanadium species of nV-MSNSs. The specific
surface area (SBET), pore diameter (Dp), and pore volume (Vp) of nV-MSNSs
decrease with the loading of vanadium species. The excessively high vanadium
loading leads to the slight connection of nanospheres, but does not affect the
assembly and growth of the three-dimensional (3D) dendritic channels. The
percentage of highly dispersed vanadium VV species gradually increases and
attains the maximum value for 5.2V-MSNSs with the loading of vanadium and then
decreases with further vanadium addition. The higher-polymerized VOx species
gradually generates above 5.2 wt % vanadium content for nV-MSNSs. The lower
polymerized VOx species appear to be more active than the higher-polymerized VOx
species. Markedly, the 5.2V-MSNSs exhibit the highest catalytic activity with the
initial propane conversion of 58% for the ODHP. The excellent catalytic
performance can be maintained after eight reaction-regeneration cycles. The
silica mesoporous frameworks can be well preserved in the reaction-regeneration
cycles; meanwhile, the highly dispersed vanadium oxide also can be fully
recovered after in situ regeneration. Hence, nV-MSNS catalysts exhibit
outstanding activity and stability, and it would have a promising application in
the DH of alkanes.
PMID- 28425292
TI - Lactone Derivatives Produced by a Phaeoacremonium sp., an Endophytic Fungus from
Senna spectabilis.
AB - Three new isoaigialones, A, B, and C (1-3), along with aigialone (4), were
isolated from the crude EtOAc extract of a Phaeoacremonium sp., an endophytic
fungus obtained from the leaves of Senna spectabilis. The structures of these
compounds were elucidated based on the analysis of spectroscopic data. Compounds
2 and 4 were active against the phytopathogenic fungi Cladosporium
cladosporioides and C. sphaerospermum. This is the first report of metabolites
produced by an Phaeoacremonium sp., associated with S. spectabilis.
PMID- 28425293
TI - Cosensitized Porphyrin System for High-Performance Solar Cells with TOF-SIMS
Analysis.
AB - To date, development of organic sensitizers has been predominately focused on
light harvesting, highest occupied molecular orbital and lowest unoccupied
molecular orbital energy levels, and the electron transferring process. In
contrast, their adsorption mode as well as the dynamic loading behavior onto
nanoporous TiO2 is rarely considered. Herein, we have employed the time-of-flight
secondary ion mass spectrometry (TOF-SIMS) to gain insight into the competitive
dye adsorption mode and kinetics in the cosensitized porphyrin system. Using
novel porphyrin dye FW-1 and D-A-pi-A featured dye WS-5, the different bond
breaking mode in TOF-SIMS and dynamic dye-loading amount during the coadsorption
process are well-compared with two different anchoring groups, such as benzoic
acid and cyanoacrylic acid. With the bombardment mode in TOF-SIMS spectra, we
have speculated that the cyano group grafts onto nanoporous TiO2 as tridentate
binding for the common anchoring unit of cyanoacrylic acid and confirmed it
through extensive first-principles density functional theory calculation by
anchoring either the carboxyl or cyano group, which shows that the cyano group
can efficiently participate in the adsorption of the WS-5 molecule onto the TiO2
nanocrystal. The grafting reinforcement interaction between the cyano group and
TiO2 in WS-5 can well-explain the rapid adsorption characteristics. A strong
coordinate bond between the lone pair of electrons on the nitrogen or oxygen atom
and the Lewis acid sites of TiO2 can increase electron injection efficiencies
with respect to those from the bond between the benzoic acid group and the
Bronsted acid sites of the TiO2 surface. Upon optimization of the coadsorption
process with dye WS-5, the photoelectric conversion efficiency based on porphyrin
dye FW-1 is increased from 6.14 to 9.72%. The study on the adsorption dynamics of
organic sensitizers with TOF-SIMS analysis might provide a new venue for
improvement of cosensitized solar cells.
PMID- 28425294
TI - Reactivity of a Base-Stabilized Germanium(I) Dimer toward Group 9 Metal(I)
Chloride and Dimanganese Decacarbonyl.
AB - The reactivity of the 2-imino-5,6-methylenedioxylphenylgermanium(I) dimer toward
group 9 metal(I) chloride and dimanganese decacarbonyl is described. [LGe:]2 (1,
L = 2-imino-5,6-methylenedioxylphenyl) underwent a disproportionation reaction
with 1.5 equiv of group 9 metal(I) chloride [MCl(cod)]2 (M = Rh, Ir) in toluene
to afford a mixture of the group 9 metallogermylene-chlorometal(I) complexes
[LGeMU-{M(cod)}2Cl] (M = Rh (2), Ir (4)) and chlorogermylene-chlorometal(I)
complexes [L(Cl)GeM(cod)Cl] (M = Rh (3), Ir (5)), respectively. The
disproportionation property of 1 is further evidenced by its reaction with 0.5
equiv of Mn2(CO)10 in refluxing toluene to form a mixture of the manganogermylene
dimer [(LGe)MU-{Mn(CO)4}]2 (7) and free ligand [LH] (8). Compounds 2-5, 7, and 8
were elucidated by NMR spectroscopy, X-ray crystallography, and DFT calculations,
respectively.
PMID- 28425295
TI - Provider and Patient Determinants of Generic Levothyroxine Prescribing: An
Electronic Health Records-Based Study.
AB - BACKGROUND: Despite the availability of generic levothyroxine products for more
than a decade, uptake of these products is poor. OBJECTIVE: We sought to evaluate
determinants of generic prescribing of levothyroxine. METHODS: In a cross
sectional analysis of electronic health records data between 2010 and 2013, we
identified adult patients with a levothyroxine prescription from a primary-care
physician (PCP) or endocrinologist. We used mixed-effect logistic regression
models with random intercepts for prescribing provider to examine predictors of
generic levothyroxine prescribing. Models include patient, prescription, and
provider fixed-effect covariates. Odds ratios (ORs) and 95% CIs were generated.
Between-provider random variation was quantified by the intraclass correlation
coefficient (ICC). RESULTS: Study patients (n = 63 838) were clustered among 941
prescribing providers within 25 ambulatory care clinics. The overall prevalence
of generic prescribing of levothyroxine was 73%. In the multivariable mixed
effect model, patients were significantly less likely to receive generic
levothyroxine from an endocrinologist than a PCP (OR = 0.43; 95% CI = 0.33-0.55;
P < 0.001). Women were less likely to receive generic levothyroxine than men from
endocrinologists (OR = 0.68; 95% CI = 0.59-0.78; P < 0.001) but not from PCPs.
Between-provider variation in generic prescribing was 18.3% in the absence of
fixed-effect covariates and could be explained marginally by patient,
prescription, and provider factors (ICC = 15.9%). CONCLUSIONS: Generic
levothyroxine prescribing differed by PCPs and endocrinologists. Residual
variation in generic prescribing, after accounting for measurable factors,
indicates the need for provider interventions or patient education aimed at
improving levothyroxine generic uptake.
PMID- 28425296
TI - Medium- to long-term persistence with non-vitamin-K oral anticoagulants in
patients with atrial fibrillation: Australian experience.
AB - OBJECTIVE: Long-term anticoagulant therapy with non-valvular atrial fibrillation
(AF) is essential to prevent thromboembolic complications, especially ischemic
stroke. This study examines medium-term persistence in AF patients using a non
vitamin-K antagonist oral anticoagulant drug (NOAC). RESEARCH DESIGN AND METHODS:
We assessed national Pharmaceutical Benefit Scheme records December 2013 through
September 2016 for initial prescription of a NOAC in a 10% random sample of
concessional patients. Key outcome measures were: (a) proportions filling first
repeat prescription, (b) proportions persisting with NOAC over 12 and 30 months
and (c) proportions switching to another NOAC or warfarin. RESULTS: A total of
8656 patients with AF initiated a NOAC (3352 apixaban, 1340 dabigatran, 3964
rivaroxaban). Mean age was 77 years, 53% male; 91% collected the first repeat
prescription for any NOAC, 70% and 57% collected any NOAC or subsequent warfarin
prescription over 12 months and 30 months respectively; 8.9% had switched to
warfarin. The proportions switching from apixaban, dabigatran and rivaroxaban to
a different NOAC were 14%, 31% and 17% respectively. In a regression model
adjusting for age, gender and comorbidity, apixaban-initiated patients over 30
months were 28% more likely to persist with any anticoagulant therapy compared
with dabigatran-initiated patients (hazard ratio [95% CI] 1.28 [1.16-1.42]) and
15% more likely to persist compared with rivaroxaban-initiated (1.15 [1.06
1.24]). Rivaroxaban-initiated patients were 12% more likely to persist compared
with dabigatran-initiated patients (1.12 [1.02-1.24]). CONCLUSIONS: Long-term
persistence with anticoagulation in patients with AF remains a concern, even with
NOACs. Patients initiated to apixaban appear to experience better medium-term
persistence compared with rivaroxaban or dabigatran.
PMID- 28425297
TI - New approaches for itaconic acid production: bottlenecks and possible remedies.
AB - Currently, growing attention is being devoted to the conversion of biomass into
value-added products, such as itaconic acid (IA), which is considered as the
cleanest alternative to petroleum-based acrylic acid. IA is an unsaturated
dicarboxylic acid that is used as a building block chemical for the production of
several value-added products such as poly-itaconic acid. IA and its derivatives
have a wide range of potential applications in textile, paint, pharmaceutical and
chemical industries. Presently, industries are producing IA on the large scale by
fermentation from glucose. However, due to the primary utility of glucose as a
food, it cannot meet the global demand for IA production in an economical way.
The main challenge, so far, has been the production technology, which does not
support cost-effective and competitive production of IA. This review discusses
the various bottlenecks faced during each step of IA production, along with
possible remedies to deal with these problems. Furthermore, it reviews the recent
progress in fermentative IA production and sheds light on different
microorganisms used, potential substrates and fermentation conditions. The review
also covers market potential for IA, which indicates that IA can be produced cost
effectively from sustainable substrates, and it has the potential to replace
petrochemicals in the near future.
PMID- 28425298
TI - Understanding self-reported difficulties in decision-making by people with autism
spectrum disorders.
AB - Autobiographical accounts and a limited research literature suggest that adults
with autism spectrum disorders can experience difficulties with decision-making.
We examined whether some of the difficulties they describe correspond to
quantifiable differences in decision-making when compared to adults in the
general population. The participants (38 intellectually able adults with autism
spectrum disorders and 40 neurotypical adults) were assessed on three tasks of
decision-making (Iowa Gambling Task, Cambridge Gamble Task and Information
Sampling Task), which quantified, respectively, decision-making performance and
relative attention to negative and positive outcomes, speed and flexibility, and
information sampling. As a caution, all analyses were repeated with a subset of
participants ( nASD = 29 and nneurotypical = 39) who were not taking
antidepressant or anxiolytic medication. Compared to the neurotypical
participants, participants with autism spectrum disorders demonstrated slower
decision-making on the Cambridge Gamble Task, and superior performance on the
Iowa Gambling Task. When those taking the medications were excluded, participants
with autism spectrum disorders also sampled more information. There were no other
differences between the groups. These processing tendencies may contribute to the
difficulties self-reported in some contexts; however, the results also highlight
strengths in autism spectrum disorders, such as a more logical approach to, and
care in, decision-making. The findings lead to recommendations for how adults
with autism spectrum disorders may be better supported with decision-making.
PMID- 28425299
TI - Posture of Patients with Sleep Apnea During Sleep.
AB - The relationship between sleep apnea syndrome (SAS) and posture during sleep has
been noted and the beneficial effect of an optimal posture on sleep apnea has
been empirically indicated. We investigated this effect in a group of subjects
that included obese patients and found that the apnea-hypopnea index (AHI) may be
normalized in the lateral position, even among patients severely affected with
apnea. Among those with intermediate or lower AHI values, sleeping in a lateral
position markedly improved the symptoms, with AHI even approaching the normal
range in many patients. A tendency was noted for AHI to rise regardless of
posture but in proportion to the increase in body mass index (BMI). In other
words, the improvement due to changes in posture became increasingly
insignificant with increase in BMI.
PMID- 28425300
TI - State of the Art.
PMID- 28425301
TI - Development of a novel rationally designed antibiotic to inhibit a nontraditional
bacterial target.
AB - The search for new nontraditional targets is a high priority in antibiotic design
today. Bacterial membrane energetics based on sodium ion circulation offers
potential alternative targets. The present work identifies the Na+-translocating
NADH:ubiquinone oxidoreductase (Na+-NQR), a key respiratory enzyme in many
microbial pathogens, as indispensible for the Chlamydia trachomatis infectious
process. Infection by Chlamydia trachomatis significantly increased first H+ and
then Na+ levels within the host mammalian cell. A newly designed furanone Na+-NQR
inhibitor, PEG-2S, blocked the changes in both H+ and Na+ levels induced by
Chlamydia trachomatis infection. It also inhibited intracellular proliferation of
Chlamydia trachomatis with a half-minimal inhibitory concentration in the
submicromolar range but did not affect the viability of mammalian cells or
bacterial species representing benign intestinal microflora. At low nanomolar
concentrations (IC50 value = 1.76 nmol/L), PEG-2S inhibited the Na+-NQR activity
in sub-bacterial membrane vesicles isolated from Vibrio cholerae. Taken together,
these results show, for the first time, that Na+-NQR is critical for the
bacterial infectious process and is susceptible to a precisely targeted
bactericidal compound in situ. The obtained data have immediate relevance for
many different diseases caused by pathogenic bacteria that rely on Na+-NQR
activity for growth, including sexually transmitted, pulmonary, oral, gum, and
ocular infections.
PMID- 28425302
TI - Probing morphological, syntactic and pragmatic knowledge through answers to wh
questions in children with SLI.
AB - PURPOSE: This study investigated aspects of morphology, syntax and pragmatics in
children with Specific Language Impairment (SLI). These areas of language were
investigated by evaluating children's answers to wh-questions. METHOD: Elicited
production methodology was used to evoke answers to three types of wh-questions.
There were 54 participants: 18 children with SLI (mean age = 5;3); 18 language
matched children matched on mean length of utterance (mean age = 3;4) and 18 age
matched children (mean age = 5;3). RESULT: The SLI group demonstrated
comprehension of the wh-questions, as revealed by their answers using the
appropriate syntactic category. Children with SLI also demonstrated knowledge of
pragmatics by using a pronoun to refer to a discourse referent that was
previously introduced as a full noun phrase. Unlike the control children,
children with SLI did not show sensitivity to one measure of the Maxim of
Quantity; they gave more full sentence answers to wh-questions in contexts when
most speakers would give a shorter, fragment answer. The tense-related morphology
was also frequently omitted from children's answers. CONCLUSION: The experiment
revealed that children with SLI did well on syntactic and pragmatic measures. The
greatest challenge was in providing tense-related morphemes in their answers to
questions.
PMID- 28425303
TI - A Retrospective Study Assessing Safety and Efficacy of Bipolar Radiofrequency
Ablation for Knee Chondral Lesions.
AB - OBJECTIVE: Bipolar radiofrequency (bRF) ablation is gaining popularity as a
treatment modality for unstable knee chondral lesions of the knee. Limited
reports of osteonecrosis and chondrolysis have been published; however, there is
little data examining the safety of this treatment in larger series. This study
aims to evaluate the safety and efficacy of bRF in the treatment of chondral
lesions encountered during knee arthroscopy. DESIGN: A retrospective evaluation
of adverse outcomes in patients that underwent treatment of chondral lesions
using bRF was undertaken. Secondary outcome measures included change in patient
reported outcome scores and its correlation to patient demographics and quality
of chondral and meniscal lesions using Chondropenia Severity Score. RESULTS: Only
2.2% and 2.7% of the patients had a postoperative complication or required a
reoperation, respectively. None of the complications were directly related to the
use of bRF. A statistically significant difference was observed when comparing
pre- and postoperative scores in all normalized categories ( P < 0.0001). No
statistically significant correlation was found between change in self-reported
scores and Chondropenia Severity Score. CONCLUSION: Bipolar radiofrequency
ablation is a safe modality in treatment of chondral lesions.
PMID- 28425304
TI - Preparation and evaluation of 1-deoxynojirimycin sustained-release pellets vs
conventional immediate-release tablets.
AB - 1-Deoxynojirimycin sustained-release pellets, which exhibit known release and
absorption profiles, are used for the treatment of diabetes mellitus. In this
study, a fluidised bed coater was employed to prepare new, drug-loaded pellets.
In the dissolution test, it was found that 1-DNJ pellets exhibited a sustained
release effect after being coated with hydroxypropyl methyl cellulose phthalate
55 S. For sustained-release pellets and immediate-release pellets, there was
significant difference in the mean cumulative drug concentration profile in
different media evaluation. In the bioavailability study, the ratio of mean
relative bioavailability of the SR pellets to the IR tablets was calculated by
the DAS from the AUC0-24 h of 1-DNJ and was found to be 117.3%. This suggested
that the behaviour in vivo of the 1-DNJ SR pellets was superior to the IR
tablets, which indicated the designed preparation method of the 1-DNJ SR pellets
was acceptable for achieving sustained release of 1-DNJ with enhanced
bioavailability.
PMID- 28425305
TI - Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery.
AB - OBJECTIVE: The aim of this work was to develop an amorphous solid
dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a
novel polymer Soluplus(r) (BASF, Germany) using a freeze-drying technique, in
order to improve dissolution and absorption through the nasal route.
SIGNIFICANCE: The small volume of fluid present in the nasal cavity limits the
absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically
insoluble and normally administered as a suspension-based nasal spray. METHODS:
The formulation was prepared through freeze-drying of polymer-drug solution. The
formulation was assessed for its physicochemical (specific surface area,
calorimetric analysis and X-ray powder diffraction), release properties and
aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells,
in order to elucidate the efficacy of the Soluplus-BUD formulation. RESULTS: The
freeze-dried Soluplus-BUD formulation (LYO) showed a porous structure with a
specific surface area of 1.4334 +/- 0.0178 m2/g. The calorimetric analysis
confirmed an interaction between BUD and Soluplus and X-ray powder diffraction
the amorphous status of the drug. The freeze-dried formulation (LYO) showed
faster release compared to both water-based suspension and dry powder commercial
products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca),
showed suitable aerodynamic characteristics for nasal drug delivery. The
permeation across RPMI 2650 nasal cell model was higher compared to a commercial
water-based BUD suspension. CONCLUSIONS: Soluplus has been shown to be a
promising polymer for the formulation of BUD amorphous solid suspension/solution.
This opens up opportunities to develop new formulations of poorly soluble drug
for nasal delivery.
PMID- 28425306
TI - Therapeutic targeting and patient selection for cancers with homologous
recombination defects.
AB - INTRODUCTION: DNA double-strand breaks (DSBs) are toxic DNA lesions that can be
repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR).
Mutations in HR genes elicit a predisposition to cancer; yet, they also result in
increased sensitivity to certain DNA damaging agents and poly (ADP-ribose)
polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it
is important that patients with HR-deficient tumors are adequately selected.
Areas covered: Herein, the authors describe the HR pathway mechanistically and
review the treatment of HR-deficient cancers, with a specific focus on PARP
inhibition for BRCA1/2-mutated breast and ovarian cancer. In addition, mechanisms
of acquired PARP inhibitor resistance are discussed. Furthermore, combination
therapies with PARP inhibitors are reviewed, in the context of both HR-deficient
and HR-proficient tumors and methods for proper patient selection are also
discussed. Expert opinion: Currently, only patients with germline or somatic
BRCA1/2 mutations are eligible for PARP inhibitor treatment and only a proportion
of patients respond. Patients with HR-deficient tumors caused by other
(epi)genetic events may also benefit from PARP inhibitor treatment. Ideally,
selection of eligible patients for PARP inhibitor treatment include a functional
HR read-out, in which cancer cells are interrogated for their ability to perform
HR repair and maintain replication fork stability.
PMID- 28425307
TI - Epidural fentanyl does not affect cervical dilation and progress of first stage
of vaginal delivery: a randomized, double-blind study.
AB - OBJECTIVE: Local anesthetics combined with opioids are commonly used in labor
epidural analgesic schemes. This study investigated if the addition of fentanyl
to epidural ropivacaine can affect cervical dilation and progress of vaginal
delivery. METHODS: Sixty-two nulliparous parturients were randomized to receive
epidurally 8 ml ropivacaine 0.2% combined with fentanyl 20 MUg (F/R-group, n =
31) or with normal saline 0.4 ml (R-group, n = 31), every hour. Rescue doses of 5
ml ropivacaine 0.2% were also administered. Measurements were performed every 60
min until full cervical dilation. The primary end-point was the time to reach 10
cm cervical dilation. Secondary outcomes were Bishop scores, mode of delivery,
total ropivacaine dose, pain, and satisfaction scores (numerical scale, 0-10).
RESULTS: Data from 60 parturients (29 in the F/R and 31 in the R-group) were
analyzed. The F/R-group had 26 vaginal deliveries (four instrumentally assisted),
and three cesarean deliveries. The R-group had 27 vaginal deliveries (six
instrumentally assisted) and 4 cesarean deliveries. Time to 10-cm cervical
dilation did not differ between the groups (4 +/- 2.4 h in the F/R-group vs 4.4
+/- 2.1 h in the R-group, p = .341). The number of women remaining in the study
every hour until full cervical dilation and Bishop scores for a 4-h period did
not differ between the groups (p = .617). Total ropivacaine dose was comparable
between the groups, but the F/R-group reported significantly lower pain (p = .01)
and higher satisfaction scores (p = .001). CONCLUSIONS: The addition of fentanyl
to ropivacaine 0.2% solution did not affect cervical dilation and progress of the
first stage of labor, but improved both analgesia and satisfaction.
PMID- 28425308
TI - The effect of molecular weights of microencapsulating polymers on viability of
mouse-cloned pancreatic beta-cells: biomaterials, osmotic forces and potential
applications in diabetes treatment.
AB - INTRODUCTION: Ideal cell-containing microcapsules should be capable of
maintaining cell viability and exhibit significant structural stability to
support cellular functionality. To date, such microcapsules remain unavailable;
thus, this study used our well-established microencapsulating methods to examine
a total of 32 different microencapsulating formulations and correlate polymers'
molecular weights (Mwt) and UDCA addition, with cell viability and microcapsules'
stability, postmicroencapsulation. METHODS: MIN6 mouse-cloned pancreatic beta
cells were microencapsulated using control (n = 16; without UDCA) and test (n =
16; with UDCA) different polymers. Confocal microscopic imaging, cell viability,
and microcapsules' stability were assessed. RESULTS: Best cell viability (>50%)
was obtained at average Mwt of 50,000 g/mol (poly-l-ornithine), followed by
110,000 g/mol (poly-l-lysine). There was no linear correlation between Mwt and
viability. Confocal imagining showed similar microcapsules' shape and cell
distribution among all different polymers' molecular weights, which suggests that
the microencapsulating method was efficient and maintained microcapsules'
uniformity. UDCA addition resulted in enhanced osmotic stability of the
microcapsules and improved cell viability, when the formulation contained 1%
polylornithine, 1% polyethylene glycol, 20% Eudragit(r) NM30D, 1%
polytetrafluoroethylene, or 5% pentamethylcyclopentasiloxane. CONCLUSIONS: UDCA
addition improved microenvironmental conditions within the microcapsules but this
effect was largely dependent on the polymer systems used.
PMID- 28425309
TI - Laboratory tests on heat treatment of ballast water using engine waste heat.
AB - Waste heat recovery from shipboard machineries could be a potential source for
heat treatment of ballast water. Similar to a shipboard schematic arrangement, a
laboratory-scale engine-heat exchanger set-up harvesting waste heat from jacket
water and exhaust gases was erected to test the level of species' mortalities.
Mortalities were also assessed under experimental conditions for cultured and
natural plankton communities at laboratory level. Effect of pump impellers on
species' mortalities were also tested. Exposures between 60 degrees C and 70
degrees C for 60 sec resulted in 80-100% mortalities. Mortalities due to pump
impeller effects were observed in the range of 70-100% for zooplankton. On the
laboratory-scale arrangement, >95% mortalities of phytoplankton, zooplankton and
bacteria were recorded. It was demonstrated that the temperature of tropical sea
waters used as secondary coolant can be raised to cause species' mortalities,
employing engine exhaust gases. The results also indicated that pump impeller
effects will enhance species' mortalities. The limitations of the shipboard
application of this method would be the large ballast volumes, flow rates and
time for treatment.
PMID- 28425310
TI - Comments on prediction of the aqueous solubility using the general solubility
equation (GSE) versus a genetic algorithm and a support vector machine model.
AB - The general solubility equation (GSE) is the state-of-the-art method for
estimating the aqueous solubilities of organic compounds. It is an extremely
simple equation that expresses aqueous solubility as a function of only two
inputs: the octanol-water partition coefficient calculated by readily available
softwares like clogP and ACD/logP, and the commonly known melting point of the
solute. Recently, Bahadori et al. proposed that their genetic algorithm support
vector machine is a "better" predictor. This paper compares the use of the of
Bahadori et al. model for the prediction of aqueous solubility to the existing
GSE model.
PMID- 28425311
TI - Later adults' cultural life scripts of middle and later adulthood.
AB - The cultural life script (CLS) refers to expected prototypical life events, often
including life transitions overwhelmingly occurring at ages 11-30. This study
outlined CLS events at ages after the majority of these events typically occur.
Participants, age 38-76, nominated events they expected a person of their age to
experience in the future. Participants rated each event's valence, importance,
prevalence, and expected age of occurrence. Events were coded into three
categories: the normative CLS for events listed by previous CLS studies,
offspring's CLS for experiencing CLS events of offspring, and later adulthood CLS
for other events nominated by at least 4% of participants. Results suggest
scripted events highlighting positivity and change. Offspring's CLS was more
positive and occurred earlier than others. Correlations emerged between event
characteristics and well-being. Results affirm the prominence of transitions in
memory, and suggest ways that older adults maintain well-being despite a cultural
narrative that emphasizes decline.
PMID- 28425312
TI - Activation of spinal alpha-7 nicotinic acetylcholine receptor shortens the
duration of remifentanil-induced postoperative hyperalgesia by upregulating KCC2
in the spinal dorsal horn in rats.
AB - Background Accumulating evidence has shown that the signal from spinal brain
derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl- cotransporter-2
plays a critical role in the process of pain hypersensitivity. The activation of
alpha-7 nicotinic acetylcholine receptors could have an analgesic effect on
remifentanil-induced postoperative hyperalgesia. Nevertheless, whether
intrathecal administration of PNU-120596, an alpha-7 nicotinic acetylcholine
receptors selective type II positive allosteric modulator, before surgery could
affect the duration of remifentanil-induced postoperative hyperalgesia remains
unknown, and the effects of alpha-7 nicotinic acetylcholine receptors activation
on the brain-derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl-
cotransporter-2 signal in the spinal dorsal horn of rats with remifentanil
induced postoperative hyperalgesia is still enigmatic. Results We demonstrated
that the brain-derived neurotrophic factor/tyrosine receptor kinase B-K+-Cl-
cotransporter-2 signal played a critical role in the development of remifentanil
induced postoperative hyperalgesia. Intrathecal administration of PNU-120596 (8
ug/kg, 15 min before surgery) was associated with earlier signs of recovery from
remifentanil-induced postoperative hyperalgesia. Simultaneously, remifentanil
induced postoperative hyperalgesia-induced K+-Cl- cotransporter-2 downregulation
was partly reversed and coincided with a decreased expression of brain-derived
neurotrophic factor/tyrosine receptor kinase B in the spinal dorsal horn,
approximately correlating with the time course of the nociceptive behavior.
Moreover, intrathecal administration of the K+-Cl- cotransporter-2 inhibitor
VU0240551 significantly reduced the analgesic effect of PNU-120596 on
remifentanil-induced postoperative hyperalgesia. Conclusions The activation of
alpha-7 nicotinic acetylcholine receptors induced a shorter duration of
remifentanil-induced postoperative hyperalgesia by restoring the brain-derived
neurotrophic factor/tyrosine receptor kinase B-K+-Cl- cotransporter-2 signal in
the spinal dorsal horn of rats, which provides new insight into treatment in
clinical postoperative pain management.
PMID- 28425313
TI - Moral Distress Among School Nurses.
AB - School nurses are well positioned to provide care to a diverse population of
school-age children, but their role and work environment can present a variety of
moral dilemmas leading to moral distress. The purpose of this study is to
identify the moral distress level that exists in school nurses and to describe
its relationship to common moral dilemmas and school nurse characteristics. Data
were collected through face-to-face attendance at school nurse meetings in North
Carolina where 307 school nurses participated in the survey. Moral distress was
measured using the moral distress thermometer, and common moral dilemmas were
identified using a researcher developed questionnaire. Almost all of the school
nurses (97.3%) experienced some degree of moral distress. Each of the common
moral dilemmas was positively correlated with moral distress levels. The findings
suggest that many of the common moral dilemmas experienced by school nurses are
strongly related to moral distress.
PMID- 28425314
TI - Effect of transmucosal corn syrup application on postoperative blood glucose
concentrations in kittens.
AB - Objectives The aim of the study was to determine the effect of a common clinical
practice, the transmucosal (TM) application of corn syrup, on postoperative blood
glucose concentrations in kittens. Methods This study was designed as a
randomized controlled trial. Seventy-five kittens between the age of 8 and 16
weeks scheduled for surgical sterilization by gonadectomy at an animal shelter
were enrolled. Kittens were randomly assigned to either a routine treatment group
that received the shelter's typical postoperative application of corn syrup
immediately following gonadectomy or to a control group that did not receive
typical treatment. Three blood glucose measurements were obtained per kitten:
baseline reading prior to preoperative examination, immediately postoperatively
and 20 mins postoperatively. The median values of the 20 min postoperative blood
glucose reading for the control and treatment groups were compared using the
Wilcoxon rank-sum test. Results Postoperative application of corn syrup to the
oral mucosa of kittens did not result in significant elevations in blood glucose
compared with controls. No kitten was hypoglycemic (?60 mg/dl) at any point
during the study. Conclusions and relevance TM application of corn syrup did not
affect postoperative blood glucose concentrations in kittens. Protocols that use
routine TM administration of corn syrup in kittens should be re-evaluated.
PMID- 28425315
TI - Caring in nursing homes to promote autonomy and participation.
AB - BACKGROUND: Autonomy and participation are threatened within the group of older
people living in nursing homes. Evidence suggests that healthcare personnel act
on behalf of older people but are still excluding them from decision-making in
everyday care. OBJECTIVE: The purpose was to describe registered nurses'
experience of caring for older people in nursing homes to promote autonomy and
participation. RESEARCH DESIGN: A descriptive design with a phenomenological
approach was used. Data were collected by semi-structured individual interviews.
Analysis was inspired by Giorgi's method. Participants and research context: A
total of 13 registered nurses from 10 nursing homes participated. Ethical
considerations: Ethical approval was obtained from the Regional Research Ethics
Committee. Informed consent was achieved and confidentiality guaranteed.
FINDINGS: The essence of caring for older people in nursing homes to promote
autonomy and participation consisted of registered nurses' awareness of older
people's frailty and the impact of illness to support health and well-being, and
awareness of acknowledgement in everyday life and trusting relationships. Paying
attention to older people by being open to the persons' wishes were aspects that
relied on registered nurses' trusting relationships with older people, their
relatives and surrounding healthcare personnel. The awareness reflected
challenges in caring to promote older people's right to autonomy and
participation in nursing homes. Registered nurses' strategies, hopes for and/or
concerns about development of everyday life in nursing homes were revealed and
mirrored their engagement in caring for older people. DISCUSSION AND CONCLUSION:
Awareness of older people's frailty in nursing homes and the importance of
maintained health and well-being were described as the main source for promoting
autonomy and participation. Everyday life and care in nursing homes needs to be
addressed from both older people's and healthcare personnel's perspectives, to
promote autonomy and participation for residents in nursing homes.
PMID- 28425316
TI - Carbon-covered mesoporous silica and its application in Rhodamine B adsorption.
AB - Modified versions of MCM-41 and SBA-15 were obtained from sucrose by carbon
deposition. The ability of the resulting materials, MCM-41 CC and SBA-15 CC, to
remove Rhodamine B from aqueous solutions was evaluated. TG/DTG, XRD, Nitrogen
Adsorption (BET), and SEM were used to characterize the materials. Adsorption was
investigated by finite bath studies. To characterize the adsorption behavior and
mechanism, kinetics and equilibrium were assessed. MCM-41 CC provided the best
adsorption results: adsorptive capacity of 11.91 mg of dye/g of material and
91.95% w/v dye removal (C0 = 50 mg L-1). The sucrose particles interacted well,
to result in improved area and micropore volume. Hence, carbon deposition can
afford materials with increased adsorptive capacity depending on the sieve
employed during their preparation.
PMID- 28425317
TI - Mortality risk factors from converting off-pump coronary artery bypass to on-pump
coronary artery bypass.
AB - INTRODUCTION: A number of large-scale retrospective studies revealed that off
pump coronary artery bypass (OPCAB) was superior to on-pump coronary artery
bypass (ONCAB). The aim of the study was to investigate risk factors for
mortality when OPCAB is converted to ONCAB. METHODS: Patients who underwent OPCAB
conversion to ONCAB at the Beijing Anzhen Hospital between January 2003 and
January 2013 were assigned to the non-survivor and survivor groups. Background
demographics, illness history and preoperative, intraoperative and postoperative
variables were compared. RESULTS: Of the 247 cases, 15.4% of the patients died.
Patients in the non-survivor group were older and more frequently had diabetes
mellitus (DM), arrhythmia, myocardial infarction (MI) in the past 30 days (all
p<0.05) and MI combined with mitral regurgitation (p<0.0001); they more
frequently had bigger left ventricular end-diastolic dimension (p=0.0019),
greater fall in blood pressure, ventricular fibrillation for longer periods,
longer conversion time and bypass graft occlusion. All patients in the non
survivor group received intra-aortic balloon pump compared to 89.5% in the
survivor group and extracorporeal membrane oxygenation was more common. Left main
coronary artery disease (OR=4.431, 95%CI: 2.440-8.048, p<0.0001), blood pressure
decline ?40 mmHg (OR=0.509, 95%CI: 0.447-0.580, p<0.0001) and time for conversion
to ONCAB ?20 min were independently associated with mortality. Rates of
postoperative complications, such as renal failure, cerebral infarction or
hemorrhage, MI and redo sternotomy, were higher in the non-survivor group.
CONCLUSIONS: Conversion from OPCAB to ONCAB is associated with high mortality.
Risk factors include left main artery disease and duration of blood pressure
decline >40 min.
PMID- 28425318
TI - Exploring families' experiences of health: contributions to a model of family
health.
AB - Child health and developmental outcomes are influenced by the health of the
family and the context created. Research suggests symptoms of poor family health
(e.g. suboptimal family interactions, parenting stress) yet there is limited
understanding of the factors which contribute to robust family health which may
unveil opportunities for targeted intervention and family health promotion. The
present study examined families' experiences of family health and factors
contributing to family health. We performed a qualitative study using
constructivist grounded theory methods to guide our understanding of family
health for families with typically developing children aged 5-18. Interviews were
conducted in family homes and all members were invited to participate. Data from
interviews were transcribed, coded, thematically analyzed, and verified with
select families. Ten families, including 10 mothers, 8 fathers, and 15 children
participated in the study. Participants described family health as a process of
balance, living purposefully, and sharing experiences together in alignment with
family identity. Mediating family health were processes of awareness and
reflection, and adapting, adjusting, and changing in response to family life
including external stress factors. Results highlight the possibility for
healthcare practitioners to facilitate families' self-reflection and awareness
about their health in order to mediate family health development.
PMID- 28425319
TI - Abandoned Luncheonettes: Can Health Promotion Stem the Loss of Social Capital?
PMID- 28425320
TI - The Art of Health Promotion.
PMID- 28425322
TI - Determinants of Health-Related Quality of Life Among Elderly: Evidence From Chi
Linh Town, Vietnam.
AB - As Vietnam confronts with the challenge of an aging population, the importance of
quality of life for elderly people becomes apparent. This article aims to assess
health-related quality of life (HRQoL) and its correlates for the elderly, using
a cross-sectional study design. A total of 1599 adults, aged 60 years and older,
were drawn from the 2016 baseline survey of Chi Linh Health and Demographic
Surveillance System (CHILILAB HDSS), which incorporated the EQ-5D, to measure
HRQoL. Data were analyzed using multivariate linear regression analyses. The EQ
5D index of the elderly was found to be 0.871 (95% confidence interval = 0.862
0.880). After controlling for covariates, there were statistically significant
associations between lower HRQoL and older age (>=80 years), lower education, no
pension, chronic disease(s), and health insurance schemes targeting poor/near
poor/priority groups. Current and future policies for improving HRQoL in old age
should be extended to cover the most vulnerable groups.
PMID- 28425323
TI - Enhanced solubility of piperine using hydrophilic carrier-based potent solid
dispersion systems.
AB - CONTEXT: Piperine alkaloid, an important constituent of black pepper, exhibits
numerous therapeutic properties, whereas its usage as a drug is limited due to
its poor solubility in aqueous medium, which leads to poor bioavailability.
OBJECTIVE: Herein, a new method has been developed to improve the solubility of
this drug based on the development of solid dispersions with improved dissolution
rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG)
and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of
piperine and carriers were also prepared for comparison. METHODS: The
physicochemical properties of the prepared solid dispersions were examined using
SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid
dispersions was recorded and compared with that of the pure piperine and physical
mixtures. The effect of these carriers on the aqueous solubility of piperine has
been investigated. RESULTS: The solid dispersions of piperine with Sor, PEG and
PVP exhibited superior performance for the dissolution of piperine with a drug
release of 70%, 76% and 89%, respectively after 2 h compared to physical mixtures
and pure piperine, which could be due to its transformation from crystalline to
amorphous form as well as the attachment of hydrophilic carriers to the surface
of poorly water-soluble piperine. CONCLUSION: Results suggest that the piperine
solid dispersions prepared with improved in vitro release exhibit potential
advantage in delivering poorly water-soluble piperine as an oral supplement.
PMID- 28425324
TI - Persistent idiopathic facial pain.
AB - Background Persistent idiopathic facial pain (PIFP) is a chronic disorder
recurring daily for more than two hours per day over more than three months, in
the absence of clinical neurological deficit. PIFP is the current terminology for
Atypical Facial Pain and is characterized by daily or near daily pain that is
initially confined but may subsequently spread. Pain cannot be attributed to any
pathological process, although traumatic neuropathic mechanisms are suspected.
When present intraorally, PIFP has been termed 'Atypical Odontalgia', and this
entity is discussed in a separate article in this special issue. PIFP is often a
difficult but important differential diagnosis among chronic facial pain
syndromes. Aim To summarize current knowledge on diagnostic criteria,
differential diagnosis, pathophysiology and management of PIFP. Methods We
present a narrative review reporting current literature and personal experience.
Additionally, we discuss and differentiate the common differential diagnoses
associated with PIFP including traumatic trigeminal neuropathies, regional
myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic
pains. Results and conclusion The underlying pathophysiology in PIFP is still
enigmatic, however neuropathic mechanisms may be relevant. PIFP needs
interdisciplinary collaboration to rule out and manage secondary causes,
psychiatric comorbidities and other facial pain syndromes, particularly
trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is
recommended at an early stage of disease, and should be addressed in the
management plan. Future research is needed to establish clear diagnostic criteria
and treatment strategies based on clinical findings and individual
pathophysiology.
PMID- 28425325
TI - Macro- and microstructural alterations of the subcortical structures in episodic
cluster headache.
AB - Background Previous functional and structural imaging studies have revealed that
subcortical structures play a key a role in pain processing. The recurring
painful episodes might trigger maladaptive plasticity or alternatively
degenerative processes that might be detected by MRI as changes in size or
microstructure. In the current investigation, we aimed to identify the macro- and
microstructural alterations of the subcortical structures in episodic cluster
headache. Methods High-resolution T1-weighted and diffusion-weighted MRI images
with 60 gradient directions were acquired from 22 patients with cluster headache
and 94 healthy controls. Surface-based segmentation analysis was used to measure
the volume of the subcortical nuclei, and mean diffusion parameters (fractional
anisotropy, mean, radial and axial diffusivity) were determined for these
structures. In order to understand whether the size and diffusion parameters
could be investigated in a headache lateralised manner, first the asymmetry of
the size and diffusion parameters of the subcortical structures was analysed.
Volumes and diffusion parameters were compared between groups and correlated with
the cumulative number of headache days. To account for the different size of the
patient and control group, a bootstrap approach was used to investigate the
stability of the findings. Results A significant lateralisation of the size
(caudate, putamen and thalamus) and the diffusion parameters of the subcortical
structures were found in normal controls. In cluster headache patients, the mean
fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity
of the right caudate nucleus and the radial diffusivity of the right pallidum
were higher. The mean anisotropy of the right pallidum was lower in patients.
Conclusion The analysis of the pathology in the subcortical structures in
episodic cluster headache reveals important features of the disease, which might
allow a deeper insight into the pathomechanism of the pain processing in this
headache condition.
PMID- 28425326
TI - Validity, reliability and sensitivity of the NORLA-6: Naming and oral reading for
language in aphasia 6-point scale.
AB - PURPOSE: Evaluation of the Naming and Oral Reading for Language in Aphasia 6
point scale (NORLA-6), a scoring system of oral reading and naming performance in
aphasia. METHOD: Data were drawn from 91 participants with non-fluent aphasia
secondary to left-hemisphere stroke across four treatment studies. To assess
validity, Spearman's correlations were calculated between the NORLA-6 and the
Gray Oral Reading Test-Fourth Edition (GORT-4) Accuracy score, GORT-4 Rate score
and the Boston Naming Test (BNT). Inter-rater and test-retest reliability were
evaluated using correlations. Sensitivity to change following oral reading
intervention was analysed using Wilcoxon Signed Rank tests between pre- and post
treatment NORLA-6 scores. RESULT: NORLA-6 performance was significantly
correlated (p < 0.001) with all reference tests (GORT-4 Accuracy, rs=0.84; GORT-4
Rate, rs= 0.61; and BNT, rs= 0.92). Inter-rater (ICC >=0.90) and test-retest (r >
0.92) reliability were both excellent. Sensitivity following oral reading
intervention was demonstrated in both oral reading accuracy and rate (p < 0.004).
CONCLUSION: The NORLA-6 is a valid and reliable measure of oral reading and
naming performance. It also demonstrates sensitivity to change in treatment
targeted behaviours. Therefore, the NORLA-6 scale may enhance outcome measurement
in both clinical practice and aphasia research.
PMID- 28425327
TI - Cross-sectional quantitative RT-PCR study of feline coronavirus viremia and
replication in peripheral blood of healthy shelter cats in Southern California.
AB - Objectives The objectives of this study were to determine the prevalence of
feline coronavirus (FCoV) viremia, and its replication in peripheral blood using
quantitative RT-PCR (qRT-PCR) methodology in a population of 205 healthy shelter
cats in Southern California, as well as to assess any possible connection to
longitudinal development of feline infectious peritonitis (FIP). Methods The
study was performed on buffy-coat samples from EDTA-anticoagulated whole blood
samples of 205 healthy shelter cats. From 50 of these cats, fecal samples were
also examined. FCoV genomic and subgenomic RNA in the buffy coats was amplified
by a total FCoV RNA qRT-PCR. Evidence for FCoV replication in peripheral blood
and feces was obtained by M gene mRNA qRT-PCR. Results Nine of 205 cats (4.4%)
were viremic by the total FCoV RNA qRT-PCR, and one of these cats had evidence of
peripheral FCoV blood replication by an FCoV mRNA qRT-PCR. The single cat with
peripheral blood replication had a unique partial M gene sequence distinct from
positive controls and previously published FCoV sequences. Neither seven of the
nine viremic cats with follow-up nor the single cat with replicating FCoV with
positive qRT-PCR results developed signs compatible with FIP within 6 months of
sample collection. Conclusions and relevance FCoV viremia and peripheral blood
replication in healthy shelter cats have a low prevalence and do not correlate
with later development of FIP in this study population, but larger case-control
studies evaluating the prognostic accuracy of the qRT-PCR assays are needed.
PMID- 28425328
TI - The use of a smartwatch as a prompting device for people with acquired brain
injury: a single case experimental design study.
AB - Prompting-based memory compensation is a potential application for smartwatches.
This study investigated the usability and efficacy of a Moto360 smartwatch as a
memory aid. Four community dwelling adults with memory difficulties following
acquired brain injury (ABI) were included in an A-B-A single case experimental
design study. Performance of everyday memory tasks was tested over six weeks with
the smartwatch and software provided during weeks three and four. Participants
were asked to use their usual memory aids and strategies during the control
phases (weeks 1-2, 5-6). Three participants successfully used the smartwatch
throughout the intervention weeks and gave positive usability ratings. A fourth
participant experienced a seizure and subsequently left the study before the
intervention phase. Three participants showed improved memory performance when
using the smartwatch. Nonoverlap of all pairs (NAP) analysis showed a non
significant small increase in memory performance between baseline and
intervention phases (mean NAP = 0.1, p = .84). There was a larger, significant
decline between the intervention and return to baseline (mean NAP = 0.58, p <
.01). The use of an off-the-shelf smartwatch device and software was feasible for
people with ABI in the community. It was effective compared to practice as usual,
although this was only apparent on withdrawal of the device.
PMID- 28425329
TI - Effects of ERK1/2 signal pathway on cardiomyocyte during glucose lowering.
AB - OBJECTIVE: This study investigated whether the extracellular signal-regulated
kinase 1/2 (ERK1/2) signal pathway affects cardiomyocyte apoptosis and the
expression of tumor necrosis factor (TNF-alpha) at different glucose-lowering
rates. METHODS: Cardiomyocytes of Wistar neonate rats were maintained in a medium
supplemented with 25 mmol/L glucosamine for 72 h. Then the medium was changed to
different concentrations of glucosamine, and all cells were divided into five
groups. The survival rate of cardiomyocyte was measured using the Cell Counting
Kit-8; cardiomyocyte apoptosis was measured using the flow cytometry instrument
and laser confocal microscope; TNF-alpha was measured using the enzyme-linked
immunosorbent assay; and ERK1/2 protein and phosphorylation were measured using
the Western blot. Cardiomyocyte apoptosis and TNF-alpha were measured again after
adding U0126. RESULTS: As the glucose-lowering rate increased, the survival rate
of cardiomyocytes increased in group B and decreased in groups C, D, and E. The
TNF-alpha concentration increased in groups B, C, and D and decreased in group E.
After 24 h, the apoptosis rate decreased in group B and increased in groups C, D,
and E. The expression of p-ERK1/2 increased in groups B, D, and E, and was the
lowest in group C. After adding U0126, the survival rate of cardiomyocyte in all
groups increased and TNF-alpha concentration decreased. CONCLUSIONS: The
influence of glucose-lowering rate on cardiomyocyte apoptosis and TNF-alpha was
caused by the p-ERK1/2 pathway. During the glucose-lowering course, the p-ERK1/2
pathway promoted cardiomyocyte apoptosis, and TNF-alpha secretion was related to
not only osmotic pressure but also ERK1/2 signal pathway activation.
PMID- 28425334
TI - Remifentanil for Sedation of Children With Traumatic Brain Injury.
AB - OBJECTIVE: To determine whether remifentanil would provide adequate sedation
while allowing frequent and reproducible neurologic assessments in children
admitted to the pediatric intensive care unit (PICU) with traumatic brain injury
(TBI) during mechanical ventilation. DESIGN: Retrospective review. SETTING:
Tertiary care PICU. PATIENTS: Thirty-eight patients over a 30-month period.
MEASUREMENTS AND MAIN RESULTS: Median age was 9 years (interquartile range [IQR]
2.25-12 years). The median Glasgow Coma Scale (GCS) was 9 (IQR: 8-10). All
patients were tracheally intubated and receiving mechanical ventilation. A
continuous infusion of remifentanil was started at 0.1 MUg/kg/min, and bolus
doses of 0.25 to 1 MUg/kg were administered every 3 to 5 minutes as needed to
reach the desired sedation level. Infusions were stopped at least hourly to
perform neurologic examinations. The median remifentanil dose was 0.25 MUg/kg/min
with an IQR of 0.1 and 0.6 MUg/kg/min. The maximum dose for any patient in the
cohort was 2 MUg/kg/min. Median duration of therapy with remifentanil was 20
hours (IQR: 8-44 hours). Adequate sedation was achieved with sedation scores
(State Behavioral Scale) meeting target levels with a median value of 100% of the
time (IQR: 79%-100%). Neurologic examinations were able to be performed within a
median of 9 minutes (IQR: 5-14 minutes) of pausing the infusion. No serious
safety events occurred. In 68% of the patients, neurologic examinations remained
reassuring during remifentanil infusion, and patients were extubated. The
remaining patients were transitioned to traditional sedative agents for long-term
management of their traumatic injuries once the neurologic status was deemed
stable. CONCLUSION: This data suggest that remifentanil is a suitable sedative
agent for use in children with TBI. It provides a rapid onset of sedation with
recovery that permits reliable and reproducible clinical examination.
PMID- 28425335
TI - The Incidence of and Risk Factors for Postintubation Hypotension in the
Immunocompromised Critically Ill Adult.
AB - OBJECTIVES: Our primary aim was to ascertain the frequency of postintubation
hypotension in immunocompromised critically ill adults with secondary aims of
arriving at potential risk factors for the development of postintubation
hypotension and its impact on patient-related outcomes. METHODS: Critically ill
adult patients (>=18 years) were included from January 1, 2010, to December 31,
2014. We defined immunocompromised as patients with any solid organ or nonsolid
organ malignancy or transplant, whether solid organ or not, requiring current
chemotherapy. Postintubation hypotension was defined as a decrease in systolic
blood pressure to less than 90 mm Hg or a decrease in mean arterial pressure to
less than 65 mm Hg or the initiation of any vasopressor medication. Patients were
then stratified based on development of postintubation hypotension. Potential
risk factors and intensive care unit (ICU) outcome metrics were electronically
captured by a validated data mart system. RESULTS: The final cohort included 269
patients. Postintubation hypotension occurred in 141 (52%; 95% confidence
interval: 46-58) patients. Several risk factors predicted postintubation
hypotension on univariate analysis; however, only Acute Physiology and Chronic
Health Evaluation III score in the first 24 hours, preintubation shock status,
and preintubation hemodynamic instability remained significant on all 4
multivariate analyses. Patients developing postintubation hypotension had higher
ICU and hospital mortality (54 [38%] vs 31 [24%], P = .01; 69 [49%] vs 47 [37%],
P = .04). CONCLUSION: Based on previous literature, we found a higher frequency
of postintubation hypotension in the immunocompromised than in the
nonimmunocompromised critically ill adult patients. Acute Physiology and Chronic
Health Evaluation III score in the first 24 hours, preintubation shock status,
and preintubation hemodynamic instability were significant predictors on
multivariate analyses. Postintubation hypotension led to higher ICU and hospital
mortality in those experiencing this complication.
PMID- 28425338
TI - Editorial.
PMID- 28425336
TI - Protective Efect of Brain-derived Neurotrophic Factor Against the Ototoxicity of
Pseudomonas aeruginosa Exotoxin A.
AB - Objective--The protective effect of brain-derived neurotrophic factor (BDNF)
against the ototoxicity resulting from exposure of Pseudomonas aeruginosa
exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF
and NG-nitro-L-arginine methyl ester (L-NAME) was also investigated. Material and
methods--Six groups of albino rats were instilled through the tympanic membrane
into the round window niche with the following solutions: saline; PaExoA; BDNF; L
NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME. Frequency-specific (2-31.5 kHz)
auditory brainstem responses were used to obtain the hearing thresholds before
and 2, 5 and 15 days after instillation. Results--PaExoA penetrated from the
middle ear into the cochlea, causing initially mixed hearing loss, followed by
persistent sensorineural hearing loss. This impairment was blocked by BDNF at 6,
8 and 10 kHz on Day 2 and at 8 kHz on Day 5. L-NAME given in combination with
BDNF did not show any additional protective effect. There were no significant
differences in the thickness of the round window membrane between control ears
and those in each instillation group. Conclusion--Our results suggest that BDNF
may protect against cochlear damage caused by PaExoA in the middle turns of the
ear.
PMID- 28425344
TI - 20 Years of fish immunotoxicology - what we know and where we are.
AB - Despite frequent field observations of impaired immune response and increased
disease incidence in contaminant-exposed wildlife populations, immunotoxic
effects are rarely considered in ecotoxicological risk assessment. The aim of
this study was to review the literature on immunotoxic effects of chemicals in
fish to quantitatively evaluate (i) which experimental approaches were used to
assess immunotoxic effects, (ii) whether immune markers exist to screen for
potential immunotoxic activities of chemicals, and (iii) how predictive those
parameters are for adverse alterations of fish immunocompetence and disease
resistance. A total of 241 publications on fish immunotoxicity were
quantitatively analyzed. The main conclusions included: (i) To date, fish
immunotoxicology focused mainly on innate immune responses and immunosuppressive
effects. (ii) In numerous studies, the experimental conditions are poorly
documented, as for instance age or sex of the fish or the rationale for the
selected exposure conditions is often missing. (iii) Although a broad variety of
parameters were used to assess immunotoxicity, the rationale for the choice of
measured parameters was often not given, remaining unclear how they link to the
suspected immunotoxic mode of action of the chemicals. (iv) At the current state
of knowledge, it is impossible to identify a set of immune parameters that could
reliably screen for immunotoxic potentials of chemicals. (v) Similarly, in fish
immunotoxicology there is insufficient understanding of how and when chemical
induced modulations of molecular/cellular immune changes relate to adverse
alterations of fish immunocompetence, although this would be crucial to include
immunotoxicity in ecotoxicological risk assessment.
PMID- 28425345
TI - Surrogate marker analysis in cancer clinical trials through time-to-event
mediation techniques.
AB - The meta-analytic approach is the gold standard for validation of surrogate
markers, but has the drawback of requiring data from several trials. We refine
modern mediation analysis techniques for time-to-event endpoints and apply them
to investigate whether pathological complete response can be used as a surrogate
marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3
trial in which locally advanced breast cancer patients were randomised to either
taxane or anthracycline based neoadjuvant chemotherapy. In the mediation
analysis, the treatment effect is decomposed into an indirect effect via
pathological complete response and the remaining direct effect. It shows that
only 4.2% of the treatment effect on disease-free survival after five years is
mediated by the treatment effect on pathological complete response. There is thus
no evidence from our analysis that pathological complete response is a valuable
surrogate marker to evaluate the effect of taxane versus anthracycline based
chemotherapies on progression free survival of locally advanced breast cancer
patients. The proposed analysis strategy is broadly applicable to mediation
analyses of time-to-event endpoints, is easy to apply and outperforms existing
strategies in terms of precision as well as robustness against model
misspecification.
PMID- 28425346
TI - Ambrisentan: a review of its use in pulmonary arterial hypertension.
AB - Pulmonary arterial hypertension (PAH) is a progressive disease defined by an
elevation in pulmonary arterial pressure that can lead to right heart failure and
death. Ambrisentan is a selective endothelin receptor antagonist approved for the
treatment of idiopathic, heritable PAH and connective tissue disease-associated
PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics
with an acceptable side-effect profile. It has also proven to be safely used in
combination with other PAH-specific medications, especially with
phosphodiesterase-5 inhibitors. In the recent randomized trial, AMBITION, it was
shown that upfront combination therapy of ambrisentan and tadalafil significantly
decreased the risk of clinical failure compared with monotherapy. This review
describes the drug profile of ambrisentan and its safety and efficacy in the
treatment of PAH.
PMID- 28425347
TI - Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal
Squamous Cell Carcinoma.
AB - The Polycomb group genes are a general class of regulators that are responsible
for maintaining homeotic gene expression throughout cell division. Polycomb group
expression plays an important role in oncogenesis of several types of human
cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus
insert site 1 are key Polycomb group proteins. Studies have shown that melanoma
nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney
leukemia virus insert site 1 is overexpressed in several human malignancies.
However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney
leukemia virus insert site 1 in esophageal squamous cell carcinoma are still
unclear. In this study, we analyzed the expression levels of melanoma nuclear
protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89
esophageal cancer tissues and paired normal mucosal tissues using
immunohistochemistry, Western blotting, and quantitative real-time polymerase
chain reaction analyses. We found that the expression of melanoma nuclear protein
18 in the carcinoma tissues was significantly lower than that in the noncancerous
mucosal tissues ( P < .05), and B-cell-specific Moloney leukemia virus insert
site 1 expression in the carcinoma tissues was significantly higher than that in
the noncancerous mucosal tissues ( P < .05). In addition, the expression of
melanoma nuclear protein 18 was correlated with clinical stage, depth of
invasion, and lymph node metastasis ( P < .05) but was not correlated with
gender, age, degree of differentiation, or disease-free survival ( P > .05). B
cell-specific Moloney leukemia virus insert site 1 expression was strongly
correlated with the degree of differentiation, clinical stage, and lymph node
metastasis ( P <.05) but was not correlated with the gender, age, depth of
invasion or disease-free survival ( P > .05). Moreover, there was a negative
correlation between melanoma nuclear protein 18 and B-cell-specific Moloney
leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma (
P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific
Moloney leukemia virus insert site 1 may play a crucial role in esophageal
squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney
leukemia virus insert site 1 may be a potential biomarker for diagnosis and
prognosis of esophageal squamous cell carcinoma.
PMID- 28425348
TI - Integration of Functional MRI and White Matter Tractography in CyberKnife
Radiosurgery.
AB - PURPOSE: To investigate the efficacy of the integration of functional magnetic
resonance imaging and diffusion-tensor imaging tractography data into CyberKnife
radiosurgery for intracranial tumor management. MATERIALS AND METHODS: Functional
neuroimaging, anatomical magnetic resonance imaging, and computed tomography
images of patients with brain lesions in critical areas were acquired before
radiosurgery. The acquired data sets were coregistered using the MIM image fusion
software module and then were imported into the CyberKnife Robotic Radiosurgery
System (Multiplan 4.0.2) for delineating the target, organs at risk, and possible
nearby functionally relevant cortical and subcortical areas. Radiation dose
distributions with and without the functionally relevant cortical and subcortical
areas into the optimization process were developed and compared. RESULTS: There
were significant differences between the treatment plans with and without the
functionally relevant cortical and subcortical areas into the optimization
process. An average 22.71% reduction in the maximum dose to functional areas was
observed. No neurological complication due to radiation damage was observed in
the follow-up period. CONCLUSION: The functional neuroimaging could be easily and
reliably integrated into the CyberKnife treatment planning. Consideration of
functional structures and fiber tracts during treatment planning could clinically
reduce the radiation doses to these critical structures, thereby preserving its
unique function of brain.
PMID- 28425349
TI - Clinical characteristics of unknown symptom onset stroke patients with and
without diffusion-weighted imaging and fluid-attenuated inversion recovery
mismatch.
AB - Background Diffusion-weighted imaging (DWI) and fluid-attenuated inversion
recovery (FLAIR) mismatch was suggested to identify stroke patients with unknown
time of symptom onset likely to be within the time window for thrombolysis. Aims
We aimed to study clinical characteristics associated with DWI-FLAIR mismatch in
patients with unknown onset stroke. Methods We analyzed baseline MRI and clinical
data from patients with acute ischemic stroke proven by DWI from WAKE-UP, an
investigator-initiated, randomized, placebo-controlled trial of MRI-based
thrombolysis in stroke patients with unknown time of symptom onset. Clinical
characteristics were compared between patients with and without DWI-FLAIR
mismatch. Results Of 699 patients included, 418 (59.8%) presented with DWI-FLAIR
mismatch. A shorter delay between last seen well and symptom recognition (p =
0.0063), a shorter delay between symptom recognition and arrival at hospital (p =
0.0025), and history of atrial fibrillation (p = 0.19) were predictors of DWI
FLAIR mismatch in multivariate analysis. All other characteristics were
comparable between groups. Conclusions There are only minor differences in
measured clinical characteristics between unknown symptom onset stroke patients
with and without DWI-FLAIR mismatch. DWI-FLAIR mismatch as an indicator of stroke
onset within 4.5 h shows no relevant association with commonly collected clinical
characteristics of stroke patients. Clinical Trial Registration URL:
http://www.clinicaltrials.gov . Unique identifier: NCT01525290; URL:
https://www.clinicaltrialsregister.eu . Unique identifier: 2011-005906-32.
PMID- 28425351
TI - Metabolic changes in methomyl poisoned rats treated by vitamin E.
AB - In this study, we developed a serum and urine metabolomic method based on gas
chromatography-mass spectrometry (GC-MS) combination with biomedical results to
evaluate the effect of vitamin E treatment on methomyl poisoning rats. The rats
were divided into three groups: the control group, methomyl poisoning group, and
vitamin E treatment group. Partial least squares discriminate analysis (PLS-DA)
showed that methomyl poisoning induced metabolic perturbations. Compared to the
control group, based on the urinary metabolomics data, the level of ribitol, l
proline, xylitol, hydrocinnamic acid, 11-cis-octadecenoic acid, octadecanoic
acid, and hexadecanoic acid of methomyl poisoning group increased, while the
level of 2,3,4-trihydroxybutyric acid, ethanimidic acid, pantothenic acid, and
retinoic acid decreased. Vitamin E pretreatment effectively normalized the levels
of metabolites in rat urine in vitamin E treatment group. There was no
significant difference in rat plasma metabolomic data after acute methomyl
poisoning. The results indicate that metabolomic method based on GC-MS may be
useful to elucidate the vitamin E treatment for methomyl poisoning.
PMID- 28425350
TI - Metabolomics approach discriminates toxicity index of pyrazinamide and its
metabolic products, pyrazinoic acid and 5-hydroxy pyrazinoic acid.
AB - Pyrazinamide (PYZ)-an essential component of primary drug regimen used for the
treatment and management of multidrug resistant or latent tuberculosis-is well
known for its hepatoxicity. However, the mechanism of PYZ-induced hepatotoxicity
is still unknown to researchers. Studies have shown that the drug is metabolized
in the liver to pyrazinoic acid (PA) and 5-hydroxy pyrazinoic acid (5-OHPA) which
individually may cause different degrees of hepatotoxicity. To evaluate this
hypothesis, PYZ, PA, and 5-OHPA were administered to albino Wistar rats orally
(respectively, at 250, 125, and 125 mg kg-1 for 28 days). Compared to normal
rats, PYZ and its metabolic products decreased the weights of dosed rats and
induced liver injury and a status of oxidative stress as assessed by combined
histopathological and biochemical analysis. Compared to normal controls, the
biochemical and morphological changes were more aberrant in PA- and 5-OHPA-dosed
rats with respect to those dosed with PYZ. Finally, the serum metabolic profiles
of rats dosed with PYZ, PA, and 5-OHPA were measured and compared with those of
normal control rats. With respect to normal control rats, the rats dosed with PYZ
and 5-OHPA showed most aberrant metabolic perturbations in their sera as compared
to those dosed with PA. Altogether, the study suggests that PYZ-induced
hepatotoxicity might be associated with its metabolized products, where 5-OHPA
contributes to a higher degree in its overall toxicity than PA.
PMID- 28425352
TI - Overdose in young children treated with anti-reflux medications: Poisons enquiry
evidence of excess 10-fold dosing errors with ranitidine.
AB - BACKGROUND: Accidental drug overdose is a common problem in young children. We
examined the influence of formulation and dose in enquiries for different gastro
oesophageal reflux disease treatments in children under 5 years to the UK's
National Poisons Information Service. METHODS: Overdose characteristics with
ranitidine, omeprazole or domperidone were compared with those of metoclopramide
and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June
2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193
omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of
these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole
cases occurred in children <5 years. In comparison, 17% (34/424) of
metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517)
of ranitidine overdose enquiries in children <5 years were under 6 months of age,
higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%),
chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In
children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine.
CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of
ranitidine enquiries, likely due to the high concentration of the syrup. This has
relevance to other liquid formulations used for non-licenced indications in young
children. Such therapeutic errors cause significant carer anxiety and healthcare
utilization. Assistance is needed from manufacturers and legislators in modifying
formulation so that drugs can be safely used in young children. Education of
prescribers and carers is also needed to reduce the incidence of such errors that
cause significant carer anxiety and healthcare utilization.
PMID- 28425361
TI - Assessment of real-time PCR cycle threshold values in Microsporum canis culture
positive and culture-negative cats in an animal shelter: a field study.
AB - Objectives Real-time PCR provides quantitative information, recorded as the cycle
threshold (Ct) value, about the number of organisms detected in a diagnostic
sample. The Ct value correlates with the number of copies of the target organism
in an inversely proportional and exponential relationship. The aim of the study
was to determine whether Ct values could be used to distinguish between culture
positive and culture-negative samples. Methods This was a retrospective analysis
of Ct values from dermatophyte PCR results in cats with suspicious skin lesions
or suspected exposure to dermatophytosis. Results One hundred and thirty-two
samples were included. Using culture as the gold standard, 28 were true
positives, 12 were false positives and 92 were true negatives. The area under the
curve for the pretreatment time point was 96.8% (95% confidence interval [CI]
94.2-99.5) compared with 74.3% (95% CI 52.6-96.0) for pooled data during
treatment. Before treatment, a Ct cut-off of <35.7 (approximate DNA count 300)
provided a sensitivity of 92.3% and specificity of 95.2%. There was no reliable
cut-off Ct value between culture-positive and culture-negative samples during
treatment. Ct values prior to treatment differed significantly between the true
positive and false-positive groups ( P = 0.0056). There was a significant
difference between the pretreatment and first and second negative culture time
points ( P = 0.0002 and P <0.0001, respectively). However, there was substantial
overlap between Ct values for true positives and true negatives, and for pre- and
intra-treatment time points. Conclusions and relevance Ct values had limited
usefulness for distinguishing between culture-positive and culture-negative cases
when field study samples were analyzed. In addition, Ct values were less reliable
than fungal culture for determining mycological cure.
PMID- 28425362
TI - To be or not to be: Stuttering and the human costs of being "un-disabled".
AB - PURPOSE: The centrality of communicating in human life means that communication
difficulties are experienced at a deeply personal level and have significant
implications for identity. Intervention methods may interact positively or
negatively with these experiences. METHOD: This paper explores this intersection
in the case of stuttering, suggesting that some intervention styles may dovetail
unhelpfully with the "mainstream" prizing of normalcy. In particular, most
"western" societies offer a performance-oriented milieu which prizes efficiency,
immediacy and competitiveness, diverting energy from the equally important work
of understanding and integrating difference. RESULT: Given that a person who
stutters speaks fluently and with a stutter, stuttering can lean toward a complex
view of disability identity-being both able and disabled. This split repertoire
invites psychologically costly efforts at being "un-disabled". CONCLUSION:
Interventions which amplify this tendency can contribute to an alienation from
self amid strivings for normalcy.
PMID- 28425363
TI - Language functioning, mental health and alexithymia in incarcerated young
offenders.
AB - PURPOSE: Previous studies describe high rates of language impairment in young
offenders; however, important correlates such as mental health status and
alexithymia have received little attention. METHOD: This study describes a cross
sectional study of the language, emotion recognition and mental health of 100
young people completing custodial sentences in New South Wales (Australia). The
sample comprised 70 young people from non-indigenous backgrounds (n = 60 male)
and 30 from indigenous backgrounds (n = 25 male). The mean age of the sample was
17.1 years. It was hypothesized that, in addition to elevated rates of language
impairment, alexithymia would be over-represented in this group. It was further
predicted that impoverished language skills would contribute to alexithymia
scores. RESULT: Only a quarter of the sample overall achieved Clinical Evaluation
of Language Fundamentals (CELF-4) Core Language Scores in the expected range;
rates of language impairment were higher in indigenous males than in non
indigenous males and in the females. Alexithymia was present in 59% of the
sample, but appeared to be associated with poor mental health, rather than with
language impairment. CONCLUSION: Interventions for young offenders (e.g.
psychological counselling, restorative justice conferencing) should be framed
around these difficulties. Validated language measures for use with young
indigenous offenders are needed.
PMID- 28425365
TI - Parental directiveness and responsivity toward young children with complex
communication needs.
AB - PURPOSE: The aim of the present study was to determine if parent responsiveness
to their children with complex communication needs (CCN) during naturalistic play
changed over an 18-month period and determine if any such changes were influenced
by the child's overall level of receptive and expressive language development,
motor development or differing play contexts. This longitudinal information is
important for early intervention speech-language pathologists and parents of
children with developmental disabilities for whom the use of parent-directed
responsivity interventions may be encouraged. METHOD: Over an 18-month period, 37
parents of young children who had physical and/or neurological disabilities
participated in three home-based parent-child play episodes. Videotapes of each
play episode were extracted and coded. RESULT: Results indicated parents who were
initially responsive showed a significant tendency to continue to be so. Early
on, parents were significantly more likely to be directive during object play
than social play and significantly more likely to interact responsively during
social play than object play. CONCLUSION: Parents of children with developmental
disabilities were not consistently less responsive to their children based on
motor or language capabilities. Previous reports of higher parental directiveness
with children who have developmental disabilities may be attributable to object
based play interactions.
PMID- 28425364
TI - Long-term effects of an intensive voice treatment for vocal fold nodules.
AB - PURPOSE: The purpose of the current study was to examine the long-term effects of
intensive voice treatment for vocal fold nodules, compared to outcomes for
patients treated with traditional voice therapy. It was hypothesised that
intensive treatment would provide comparable maintenance of vocal function, voice
quality, and patients' perception of quality-of-life when compared with
traditional treatment at 6 month follow-up. METHOD: Thirty-six women diagnosed
with bilateral vocal fold nodules who were treated with either traditional (n =
20; once a week for 8 weeks) or intensive (n = 16; eight sessions within 3 weeks)
therapy. Each participant completed voice, stroboscopic, and acoustic assessments
and the Voice Handicap Index before, immediately post and 6 months post
treatment. RESULT: Results revealed most improved perceptual, stroboscopic and
acoustic parameters were maintained in both groups at 6 months post-treatment,
with no significant differences between the two groups. In addition, both groups
maintained satisfaction on their perception of vocal function, with no
significant difference between the two groups. CONCLUSION: The investigation
provided further evidence that individuals with vocal fold nodules are able to
maintain improved voice quality and vocal health following intensive voice
treatment to a similar degree to traditional voice treatment.
PMID- 28425366
TI - Expressive and receptive language skills in preschool children from a socially
disadvantaged area.
AB - PURPOSE: Evidence suggests that children present with receptive language skills
that are equivalent to or more advanced than expressive language skills. This
profile holds true for typical and delayed language development. This study aimed
to determine if such a profile existed for preschool children from an area of
social deprivation and to investigate if particular language skills influence any
differences found between expressive and receptive skills. METHOD: Data from 187
CELF P2 UK assessments conducted on preschool children from two socially
disadvantaged areas in a city in southern Ireland. RESULT: A significant
difference was found between Receptive Language Index (RLI) and Expressive
Language Index (ELI) scores with Receptive scores found to be lower than
Expressive scores. The majority (78.6%) of participants had a lower Receptive
Language than Expressive score (RLI < ELI), 18.2% of participants had a higher
Receptive score than score (RLI > ELI), with very few (3.2%) having the same
Receptive and Expressive scores (RLI = ELI). Scores for the Concepts and
Following Directions (receptive) sub-test were significantly lower than for the
other receptive sub tests, while scores for the Expressive Vocabulary sub-test
were significantly higher than for the other expressive sub tests. CONCLUSION:
The finding of more advanced expressive than receptive language skills in
socially deprived preschool children is previously unreported and clinically
relevant for speech-language pathologists in identifying the needs of this
population.
PMID- 28425367
TI - Comparing alternate learning pathways within a problem-based learning speech
language pathology curriculum.
AB - PURPOSE: This qualitative study investigated the learning process for speech
language pathology (SLP) students engaging in a problem-based learning (PBL)
curriculum and compared the perspectives of students from two pathways. METHOD:
Sixteen final-year SLP students participated in one of four focus groups. Half
the participants entered the course directly via an undergraduate pathway and the
other half entered via a graduate entry pathway. Each focus group comprised two
students from each pathway. Data were generated via a semi-structured interview
and analysed thematically. RESULT: Regardless of participants' pathway, many
similar themes about factors that influenced their expectations prior to PBL
commencing as well as their actual PBL experiences were raised. Participants
believed that PBL was a productive way to learn and to develop clinical
competencies. Many were critical of variations in PBL facilitation styles and
were sensitive to changes in facilitators. The majority of participants viewed
experiential opportunities to engage in PBL prior to commencement of semester as
advantageous. CONCLUSION: Combining students with different backgrounds has many
advantages to the PBL learning process. Regardless of prior experiences, all
students must be sufficiently prepared. Furthermore, the facilitator has a
crucial role with the potential to optimise or detract from the learning
experience.
PMID- 28425368
TI - The relationship between labial vibrotactile detection and pure-tone hearing
thresholds in healthy, ageing adults.
AB - PURPOSE: Orofacial anatomy is unique from other body systems in that oral
musculature inserts directly into the underlying cutaneous skin, allowing for
tight temporal synchronicity between somatosensory and auditory performance
feedback to maintain correct orofacial behaviours across the lifespan.
Unfortunately, little is currently known regarding the changes in orofacial
sensory capacities associated with ageing and how these somatosensory and
auditory changes may impact feedback during functional behaviours such as speech
or swallowing. The purpose of this descriptive study was to begin assessing the
relationship between the auditory and labial somatosensory system in healthy
ageing adults. METHOD: Pure-tone hearing thresholds were determined for 500,
1000, 2000 and 4000 Hz. Using a 2-alternative forced choice paradigm, 60 adults
(19-84 years) completed vibrotactile detection thresholds (VDT) at the 5 and 10
Hz test frequencies. RESULT: A significant difference for age by group was
identified at the 5 Hz test frequency. Spearman Correlations identified a
significant correlation between age and pure tone hearing thresholds and the 5 Hz
test frequency threshold. CONCLUSION: A relationship between pure tone hearing
thresholds and labial somatosensory was identified. Future studies will begin the
processing of modelling the complex multivariate sensorimotor relationship in
healthy individuals before moving to a disordered population.
PMID- 28425373
TI - Calm child programme: Parental programme for anxiety in children and young people
with autism spectrum disorder and intellectual disabilities.
AB - Children with autism spectrum disorder (ASD) and intellectual disabilities (IDs)
are more vulnerable to experiencing anxiety disorders. Parental involvement in
intervention is crucial for successful management of the interventions in the
population of people with ASDs. This article describes the design and evaluation
of parenting programme for anxiety disorders in children and young people with
ASD and ID. In phase 1 semi-structured interviews were conducted to explore
management strategies for anxiety at home and in school settings. A total of 34
participants (14 parents, 20 teachers) participated in the interviews. A Delphi
process was conducted with health professionals to develop consensus on
appropriate anxiety interventions. In phase 2 the intervention programme was
implemented by seven parents who also participated in focus group to evaluate the
developed programme. A parental programme, calm child programme (CCP), was
developed, implemented and evaluated. The evaluations show significant decrease
in children's anxiety as a result of implementing the programme. This study
contributes further evidence to parental involvement in interventions for
children and young people with ASD and IDs. The CCP is a useful and cost
effective approach in enabling parents to provide anxiety interventions in a home
setting.
PMID- 28425386
TI - 22nd Annual RIMS Conference 2017.
PMID- 28425387
TI - Zebra-borne neurotropic equid herpesvirus 1 meningoencephalitis in a Thomson's
gazelle ( Eudorcas thomsonii).
AB - We describe the histopathologic, immunohistochemical, and molecular features of a
case of meningoencephalitis in a Thomson's gazelle ( Eudorcas thomsonii)
naturally infected with zebra-borne equid herpesvirus 1 (EHV-1) and the
implications for the molecular detection of zebra-borne EHV-1. A 4-y-old female
Thomson's gazelle was submitted for postmortem examination; no gross
abnormalities were noted except for meningeal congestion. Microscopic evaluation
demonstrated multifocal nonsuppurative meningoencephalitis with intranuclear
eosinophilic and amphophilic inclusion bodies and EHV-9 antigen in neurons. PCR
demonstrated the presence of a herpesvirus with a nucleotide sequence 99-100%
identical to the corresponding sequences of zebra-borne EHV-1 and of EHV-9
strains. To determine whether EHV-1 or EHV-9 was involved, a PCR with a specific
primer set for EHV-9 ORF59/60 was used. The sequence was identical to that of 3
recognized zebra-borne EHV-1 strains and 91% similar to that of EHV-9. This
isolate was designated as strain LM2014. The partial glycoprotein G ( gG) gene
sequence of LM2014 was also identical to the sequence of 2 zebra-borne EHV-1
strains (T-529 isolated from an onager, 94-137 from a Thomson's gazelle). The
histologic lesions of encephalitis and antigen localization in this gazelle
indicate prominent viral neurotropism, and lesions were very similar to those
seen in EHV-1- and EHV-9-infected non-equid species. Histologic lesions caused by
EHV-9 and zebra-borne EHV-1 are therefore indistinguishable.
PMID- 28425388
TI - Lower Bound on Estimation Variance of the Ultrasonic Attenuation Coefficient
Using the Spectral-Difference Reference-phantom Method.
AB - Ultrasonic attenuation is one of the primary parameters of interest in
Quantitative Ultrasound (QUS). Non-invasive monitoring of tissue attenuation can
provide valuable diagnostic and prognostic information to the physician. The
Reference Phantom Method (RPM) was introduced as a way of mitigating some of the
system-related effects and biases to facilitate clinical QUS applications. In
this paper, under the assumption of diffuse scattering, a probabilistic model of
the backscattered signal spectrum is used to derive a theoretical lower bound on
the estimation variance of the attenuation coefficient using the Spectral
Difference RPM. The theoretical lower bound is compared to simulated and
experimental attenuation estimation statistics in tissue-mimicking (TM) phantoms.
Estimation standard deviation (STD) of the sample attenuation in a region of
interest (ROI) of the TM phantom is measured for various combinations of
processing parameters, including Radio-Frequency (RF) data block length (i.e.,
window length) from 3 to 17 mm, RF data block width from 10 to 100 A-lines, and
number of RF data blocks per attenuation estimation ROI from 3 to 10. In addition
to the Spectral-Difference RPM, local attenuation estimation for simulated and
experimental data sets was also performed using a modified implementation of the
Spectral Fit Method (SFM). Estimation statistics of the SFM are compared to
theoretical variance predictions from the literature.1 Measured STD curves are
observed to lie above the theoretical lower bound curves, thus experimentally
verifying the validity of the derived bounds. This theoretical framework benefits
tissue characterization efforts by isolating processing parameter ranges that
could provide required precision levels in estimation of the ultrasonic
attenuation coefficient using Spectral Difference methods.
PMID- 28425389
TI - Simultaneous Analysis of Simple Coumarins and Furocoumarines in Cigarettes by
Solid-Phase Extraction with Gas Chromatography-Mass Spectrometry.
AB - A sensitive, high-throughput analytical method based on a GC-MS method was
established for the simultaneous quantitative determination of two categories of
harmful coumarins: simple coumarins (coumarin, 6-methylcoumarin, 7
methoxycoumarin, 3,4-dihydrocoumarin, and 7-ethoxy-4-methylcoumarin) and
furocoumarines (psoralen, 8-methoxypsoralen, 5-methoxypsoralen, and trioxysalen).
The nine analytes were extracted with ethyl acetate, purified with Oasis HLB
solid-phase extraction (SPE) cartridges, and identified and quantitatively
determined by GC-MS in selected-ion monitoring mode. The LODs and LOQs of these
compounds were in the ranges of 12.5-21.2 and 41.6-70.0 MUg/kg, respectively.
Average recoveries for the nine analytes ranged from 72.7 to 86.6% at LOQ, 1.5*
LOQ, and 2* LOQ spike levels, with RSDs that were typically lower than 5.1%. The
SPE-GC-MS method developed in this study was initially applied to research
coumarins in cigarette samples; it proved to be accurate, sensitive, convenient,
and practical.
PMID- 28425391
TI - New Analytical Applications for Food Antigens.
PMID- 28425392
TI - An Improved Method for the Quantification of Thiamine (Vitamin B1) in Cocoa
Containing Beverage Powders.
AB - The purpose of this work was to understand low recoveries of thiamine (vitamin
B1) when extracted from cocoa-containing beverage powders fortified with water
soluble vitamin B1, and to develop and validate a new procedure to improve these
results. Based on the literature, previous trials have focused on two main
factors: pH value prior to paper filtration and the need for solid-phase
extraction (SPE) clean up. We demonstrate that by following European Standard EN
14122, recovery of thiamine in cocoa-containing beverage powders is low and
dependent on the test portion (86 and 72% for 0.5 and 1.5 g test portions,
respectively). Our improved method resolved this problem by keeping the pH low
(around 1) prior to paper filtration, leading to a 96.3% recovery and high
precision (RSDr of 3.5%). The use of strong cation-exchange SPE cartridges for
cleanup prior to the thiamine oxidation reaction proved to be essential. A
comparison between our improved method and EN 14122 on nine cocoa-containing
beverage samples available on local market from different manufacturers showed a
systematic increase in thiamine content (up to 70%) when the improved method was
applied. The highest difference was observed for the sample that contained the
highest amount of cocoa. However, for beverage powders that contained both cocoa
and milk, no difference was observed.
PMID- 28425393
TI - Magnetic Graphene Oxide as an Efficient Adsorbent for the Separation and
Preconcentration of Cu(II), Pb(II), and Cd(II) from Environmental Samples.
AB - The separation and preconcentration of copper(II), lead(II), and cadmium(II) ions
on magnetic graphene oxide (MGO) by solid-phase extraction was carried out.
Quantitative recovery was obtained by adsorption of analytes on MGO at pH 6 and
elution of 3 M HNO3 in 10% acetone. To optimize the presented method, the effects
of various parameters-including pH, eluent conditions, and vortex time-were
examined. Matrix effects were also investigated. Mean recoveries of the analytes
were between 95 and 105%. The proposed method was validated by applying it to
certified reference materials. Addition and recovery tests were also performed.
The method was applied to verify the analyte content of several water and food
samples.
PMID- 28425394
TI - Near-Infrared Spectrum Detection of Wheat Gluten Protein Content Based on a
Combined Filtering Method.
AB - To eliminate the random error of the derivative near-IR (NIR) spectrum and to
improve model stability and the prediction accuracy of the gluten protein
content, a combined method is proposed for pretreatment of the NIR spectrum based
on both empirical mode decomposition and the wavelet soft-threshold method. The
principle and the steps of the method are introduced and the denoising effect is
evaluated. The wheat gluten protein content is calculated based on the denoised
spectrum, and the results are compared with those of the nine-point smoothing
method and the wavelet soft-threshold method. Experimental results show that the
proposed combined method is effective in completing pretreatment of the NIR
spectrum, and the proposed method improves the accuracy of detection of wheat
gluten protein content from the NIR spectrum.
PMID- 28425396
TI - Development and Single-Laboratory Validation of a Liquid Chromatography Tandem
Mass Spectrometry Method for Quantitation of Tetrodotoxin in Mussels and Oysters.
AB - In recent years, evidence has grown for the presence of tetrodotoxin (TTX) in
bivalve mollusks, leading to the potential for consumers of contaminated products
to be affected by Tetrodotoxin Shellfish Poisoning (TSP). A single-laboratory
validation was conducted for the hydrophilic interaction LC (HILIC) tandem MS
(MS/MS) analysis of TTX in common mussels and Pacific oysters-the bivalve species
that have been found to contain TTXs in the United Kingdom in recent years. The
method consists of a single-step dispersive extraction in 1% acetic acid,
followed by a carbon SPE cleanup step before dilution and instrumental analysis.
The full method was developed as a rapid tool for the quantitation of TTX, as
well as for the associated analogs 4-epi-TTX; 5,6,11-trideoxy TTX; 11-nor TTX-6
ol; 5-deoxy TTX; and 4,9-anhydro TTX. The method can also be run as the
acquisition of TTX together with paralytic shellfish toxins. Results demonstrated
acceptable method performance characteristics for specificity, linearity,
recovery, ruggedness, repeatability, matrix variability, and within-laboratory
reproducibility for the analysis of TTX. The LOD and LOQ were fit-for-purpose in
comparison to the current action limit for TTX enforced in The Netherlands. In
addition, aspects of method performance (LOD, LOQ, and within-laboratory
reproducibility) were found to be satisfactory for three other TTX analogs (11
nor TTX-6-ol, 5-deoxy TTX, and 4,9-anhydro TTX). The method was found to be
practical and suitable for use in regulatory testing, providing rapid turnaround
of sample analysis. Plans currently underway on a full collaborative study to
validate a HILIC-MS/MS method for paralytic shellfish poisoning toxins will be
extended to include TTX in order to generate international acceptance, ultimately
for use as an alternative official control testing method should regulatory
controls be adopted.
PMID- 28425397
TI - Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients
Treated with Ledipasvir/Sofosbuvir Plus Ribavirin Pretransplant.
PMID- 28425398
TI - Prospective Indian Study of DILI with Confirmed Causality Using the Roussel Uclaf
Causality Assessment Method (RUCAM): A report of Excellence.
PMID- 28425399
TI - Liver Transplantation as Cure of Hepatocellular Carcinoma: It is not a Matter of
Time, it is a Matter of Tumor Biology.
PMID- 28425400
TI - The Direct-Acting Antivirals for Hepatitis C Virus and the Risk for
Hepatocellular Carcinoma.
AB - The increase of incidences of Hepatocellular Carcinoma (HCC) will continue in the
next decades. The therapies about hepatitis C infection has been questioned as a
risk factor. Some authors emphasized that sustained virologic response (SVR) with
interferon-based therapy reduced the risk of developing HCC. In contrast, some
publications that to suggest an increasing risk of HCC in patients treated with
Direct-Acting Antivirals (DAA). Whether these therapies are associated with an
increased risk of HCC remains to be studied and continued long-term observational
studies will be needed. The goal in HCV care needs to go beyond merely achieving
an SVR.
PMID- 28425401
TI - MRE in NAFLD: Promising but Further Validation is Required.
AB - MR elastography is a novel method for non-invasive fibrosis assessment, not yet
sufficiently validated. In a recent study in 104 patients Park, Gastroenterology
2017; 152: 598-602), MRE was compared to transient elastography for the diagnosis
of fibrosis is nonalcoholic fatty liver disease. The current viewpoint critically
appraises this study.
PMID- 28425402
TI - What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the
Liver. Is There Any Place for Surgery?
AB - Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in
the vast majority of the cases in young women. FNH represents a polyclonal lesion
characterized by local vascular abnormalities and is a truly benign lesion
without any potential for malignant transformation. A retrospective single
institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review
of studies reporting surgical therapy of overall 293 patients with FNH was
performed. Indications for resection with a focus on diagnostic workup, patient
selection, surgical mode and operative mortality and morbidity have been
analysed. Ninety three patients underwent elective hepatectomy and 134 patients
observation alone, where median follow-up was 107 months. Postoperative
complications were recorded in 14 patients, 92% of patients reported an
improvement with respect to their symptoms. Overall among 293 patients underwent
surgery in the series, included to this review, there was a morbidity of 13%,
where median follow-up was 53 months. Systematic follow-up remains the gold
standard in asymptomatic patients with FNH. However elective surgery should be
considered in symptomatic patients, in those with marked enlargement and in case
of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low
morbidity and very good long term results as far as quality of life after surgery
is concerned and surely an integral part of the modern management of FNH.
PMID- 28425403
TI - The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.
AB - INTRODUCTION: HCV has been suspected to potentially cause degenerations in the
central nervous system. Parkinson's disease is the second most common
neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's
disease among patients with HCV infection. MATERIAL AND METHODS: For this study,
we used Medicare database from 2005-2010. Medicare database contains information
on enrollment, coverage, diagnosis recorded with International Classification of
Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files,
Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0.
Other study variables were; age, gender, race (White and No White), and Medicare
eligibility status. Simple distribution comparison by HCV status examined with t
test for numerical variables and ?2 test for categorical variables in the main
analytical cohort as well as in the propensity score matched cohort. RESULTS: A
total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was
identified among over 47 million claims. Of these, 6040 patients (0.5%) were
infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004)
of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups
matched for age, gender and race, the prevalence of Parkinson's disease was
similar between HCV and Non-HCV groups (P > 0.05). DISCUSSION: This study
revealed that, among Medicare population, HCV was not associated with Parkinson
disease.
PMID- 28425404
TI - Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in
Hepatitis C: A Meta-Analysis.
AB - BACKGROUND AND RATIONALE: Many different non-invasive methods have been studied
with the purpose of staging liver fibrosis. The objective of this study was
verifying if transient elastography is superior to aspartate aminotransferase to
platelet ratio index for staging fibrosis in patients with chronic hepatitis C.
MATERIAL AND METHODS: A systematic review with meta-analysis of studies which
evaluated both non-invasive tests and used biopsy as the reference standard was
performed. A random-effects model was used, anticipating heterogeneity among
studies. Diagnostic odds ratio was the main effect measure, and summary receiver
operating characteristic curves were created. A sensitivity analysis was planned,
in which the meta-analysis would be repeated excluding each study at a time.
RESULTS: Eight studies were included in the meta-analysis. Regarding the
prediction of significant fibrosis, transient elastography and aspartate
aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95%
confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94)
respectively. Concerning the prediction of cirrhosis, transient elastography and
aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of
66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval
= 4.88-11.43) respectively. CONCLUSION: In conclusion, there was no evidence of
significant superiority of transient elastography over aspartate aminotransferase
to platelet ratio index regarding the prediction of significant fibrosis, but the
former proved to be better than the latter concerning prediction of cirrhosis.
PMID- 28425405
TI - Cost-Effectiveness and Clinical Impact of Antiviral Strategies of HBeAg-Positive
and -Negative Chronic Hepatitis B.
AB - INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and
healthcare costs. Virologic response achieved with antivirals is associated with
progression avoidance. This study aimed to estimate the efficiency and clinical
impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov
model estimated lifetime complications and direct costs in both, HBeAg-positive
and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2
(100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir
or entecavir, were compared to no treatment. Progression was based on HBV-DNA
levels. Rescue therapy with oral antivirals was applied for peg-IFN failure.
Disease costs (C, 2014) and utilities were obtained from literature. RESULTS:
Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive,
2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg
positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128
and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and
up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost
increased up to C102,841 (strategy 1) and C105,408 (strategy 2) in HBeAg
positive, and C85,858 and C93,754 in HBeAg-negative. A C1,581/QALY gained ratio
was estimated versus the natural history for both strategies. In conclusion,
increasing antiviral coverage would be efficient, reducing complications.
PMID- 28425406
TI - Curing Chronic Hepatitis C: A Cost Comparison of the Combination Simeprevir Plus
Sofosbuvir vs. Protease-Inhibitor-Based Triple Therapy.
AB - INTRODUCTION: Interferon-free, multi-direct acting antiviral (DAA) therapy for
chronic hepatitis C virus (HCV) infection is highly effective and well tolerated,
but costly. To gain perspective on the evolving economics of HCV therapy, we
compared the cost per cure of a multi-DAA regimen with the prior standard of
triple therapy. MATERIAL AND METHODS: Patients infected with HCV genotype 1 who
were treated through the University of Colorado Hepatology Clinic between May
2011 and December 2014 comprised the study population. The multi-DAA regimen of
simeprevir plus sofosbuvir (SMV/SOF) was compared to the triple therapy regimen
consisting of peginterferon and ribavirin, with either boceprevir or telaprevir
(TT). Sustained-virologic response (SVR) rates, total costs per treatment and
adverse events were recorded. Total cost per SVR were compared for the two
treatments, controlling for patient demographics and clinical characteristics.
RESULTS: One hundred eighty-three patients received SMV/SOF (n = 70) or TT (n =
113). Patients receiving SMV/SOF were older, more treatment experienced, and had
a higher stage of fibrosis. SVRs were 86% and 59%, average total costs per
patient were $152,775 and $95,943, and average total costs per SVR were $178,237
vs. $161,813.49 for SMV/SOF and TT groups, respectively. Medication costs
accounted for 98% of SMV/SOF and 85% of TT treatment costs. CONCLUSION: The high
cure rate of multi-DAA treatment of HCV is offset by the high costs of the DAAs,
such that the cost per cure from TT to multi-DAA therapy has been relatively
constant. In order to cure more patients, either additional financial resources
will need to be allocated to the treatment of HCV or drug costs will need to be
reduced.
PMID- 28425407
TI - Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients
Treated with Ledipasvir / Sofosbuvir Plus Ribavirin Pretransplant.
AB - INTRODUCTION: Recurrence of HCV infection in patients with chronic hepatitis C
virus (HCV) at the time of liver transplantation is nearly universal and reduces
the likelihood of graft and patient survival. MATERIALS AND METHODS: We evaluated
outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who
received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or
up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all
patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients
were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients
underwent transplant prior to completing assigned treatment, with 4 treated for <
12 weeks. The primary endpoint was posttransplant virologic response 12 weeks
after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last
measurement prior to transplant. RESULTS: Overall, 94% (16/17) achieved pTVR12.
All who achieved pTVR12 received at least 11 weeks of treatment. The single
patient who did not achieve pTVR12 discontinued study drug on day 21 and
underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL
at post-transplant week 2 but died 15 days post-transplant because of multi-organ
failure and septic shock. CONCLUSION: Among a small population of HCV patients
with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus
ribavirin prior to liver transplantation was maintained after transplantation,
even if treatment was stopped early. Administration of ledipasvir / sofosbuvir
plus ribavirin before liver transplant can prevent post-transplant HCV
recurrence.
PMID- 28425408
TI - Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease:
a Systematic Review and Meta-Analysis.
AB - INTRODUCTION AND AIM: Endogenous sex hormones are associated with the risk of
diabetes and metabolic syndrome. Recent studies suggested the role of these
hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic
review and meta-analysis of observational studies investigating the association
between sex hormones and NAFLD. MATERIAL AND METHODS: A comprehensive search of
the databases of the MEDLINE and EMBASE was performed from inception through
April 2016. The inclusion criterion was the observational studies that assessed
the association of serum total testosterone (TT) and sex-hormone binding globulin
(SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95%
confidence intervals (CI) comparing between subjects with and without NAFLD by
using random-effects model. RESULTS: Sixteen trials comprising 13,721 men and
5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD
(MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men
with higher TT levels had lower odds of NAFLD whereas higher TT levels increased
the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients
with NAFLD than controls and this inverse association was stronger in women than
men and higher SHBG levels were associated with reduced odds of NAFLD.
CONCLUSION: Our meta-analysis demonstrated a sex-dependent association between TT
and NAFLD. Lower TT levels are associated with men with NAFLD and inversely
associated with women with NAFLD, whereas higher SHBG levels are associated with
lower NAFLD odds in both men and women.
PMID- 28425409
TI - The Utilization of Palliative Care Services in Patients with Cirrhosis who have
been Denied Liver Transplantation: A Single Center Retrospective Review.
AB - INTRODUCTION AND AIM: Utilization of palliative care services in patients dying
of end-stage liver disease (ESLD) is understudied. We performed a retrospective
review of palliative care services among patients with ESLD unsuitable for liver
transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased
ESLD patients considered unsuitable for LT from 2007-2012 were identified.
Patients were excluded if they received a transplant, had an incomplete workup,
were lost to follow up or whose condition improved so LT was not needed. Of the
1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients
(34.4%) received an inpatient palliative care (PC) consultation and forty-one
patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%)
transitioned to comfort measures without PC consultation (median survival < 1
day). The median interval between LT denial and PC consultation or hospice was 28
days. Median survival after PC consult or hospice referral was 15 days. In
conclusion, in a single center retrospective review of ESLD patients, palliative
care services, when utilized, were for care at the very end of life. Without
consultation, aggressive interventions continued until hours before death. We
propose that ESLD patients could benefit from PC consultation at time of LT
evaluation or based on MELD scores.
PMID- 28425410
TI - Liver Transplantation for Hepatocellular Carcinoma: Impact of Wait Time at a
Single Center.
AB - INTRODUCTION AND AIM: Liver transplantation (LT) provides durable survival for
hepatocellular carcinoma (HCC). However, there is continuing debate concerning
the impact of wait time and acceptable tumor burden on outcomes after LT. We
sought to review outcomes of LT for HCC at a single, large U.S. center, examining
the influence of wait time on post-LT outcomes. MATERIAL AND METHODS: We reviewed
LT for HCC at Mayo Clinic in Florida from 1/1/2003 until 6/30/2014. Follow up was
updated through 8/1/ 2015. RESULTS: From 2003-2014, 978 patients were referred
for management of HCC. 376 patients were transplanted for presumed HCC within
Milan criteria, and the results of these 376 cases were analyzed. The median
diagnosis to LT time was 183 days (8 - 4,337), and median transplant list wait
time was 62 days (0 - 1815). There was no statistical difference in recurrence
free or overall survival for those with wait time of less than or greater than
180 days from diagnosis of HCC to LT. The most important predictor of long term
survival after LT was HCC recurrence (HR: 18.61, p < 0.001). Recurrences of HCC
as well as survival were predicted by factors related to tumor biology, including
histopathological grade, vascular invasion, and pre-LT serum alpha-fetoprotein
levels. Disease recurrence occurred in 13%. The overall 5-year patient survival
was 65.8%, while the probability of 5-year recurrence-free survival was 62.2%.
CONCLUSIONS: In this large, single-center experience with long-term data, factors
of tumor biology, but not a longer wait time, were associated with recurrence
free and overall survival.
PMID- 28425411
TI - Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection
In Patients with Low Hepatitis B Viral Load.
AB - BACKGROUND: A retrospective cohort study was conducted to investigate the effect
of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (<
2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC)
after curative resection. MATERIAL AND METHODS: A total of 192 patients with low
viral load who had received curative resection of pathologically confirmed HCC
were analyzed to determine the factors affecting prognosis. The risk factors for
survival, early and late recurrence (2 years as a cut-off) were studied. RESULTS:
The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-,
and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively.
The cumulative recurrence rates at 1-, 3, and 5-year after curative resection
were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels
(> 250 IU/mL) had significantly lower survival rates than those with low HBsAg
levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed
that patients with high HBsAg levels had a significantly higher late recurrence
incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P =
0.026), but did not have a significantly higher risk of early recurrence
postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate
analysis revealed that HBsAg > 250 IU/mL was an independent risk factor
associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032).
CONCLUSIONS: HBsAg > 250 IU/mL at the time of tumor resection was an independent
risk factor for late recurrence in low viral load HCC patients.
PMID- 28425412
TI - Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse
Probability of Treatment Weighted Analysis.
AB - BACKGROUND: Evidence supporting benefit of hepatocellular carcinoma (HCC)
surveillance in reducing mortality is not well-established. The effect of HCC
surveillance in reducing mortality was assessed by an inverse probability of
treatment weighting (IPTW)-based analysis controlled for inherent bias and
confounders in observational studies. MATERIAL AND METHODS: This retrospective
cohort study was conducted on 446 patients diagnosed with HCC between 2007 and
2013 at a major referral center. Surveillance was defined as having at least 1
ultrasound test within a year before HCC diagnosis. Primary outcome was survival
estimated using the Kaplan-Meier method with lead-time bias adjustment and
compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval
(CI) were computed using conventional Cox and weighted Cox proportional hazards
analysis with IPTW adjustment. RESULTS: Of the 446 patients, 103 (23.1%) were
diagnosed with HCC through surveillance. The surveillance group had more patients
with the Barcelona-Clinic Liver Cancer stage A (80.6% vs. 33.8%, P < 0.0001),
more patients eligible for potentially curative treatment (73.8% vs. 44.9%, P <
0.0001), and longer median survival (49.6 vs. 15.9 months, P < 0.0001). By
conventional multivariate Cox analysis, HR (95% CI) of surveillance was 0.63
(0.45-0.87), P = 0.005. The estimated effect of surveillance remained similar in
the IPTW-adjusted Cox analysis (HR: 0.57; 95% CI: 0.43-0.76, P < 0.001).
CONCLUSIONS: HCC surveillance by ultrasound is associated with a 37% reduction in
mortality. Even though surveillance is recommended in all guidelines, but in
practice, it is underutilized. Interventions are needed to increase surveillance
rate for improving HCC outcome.
PMID- 28425413
TI - Ursodeoxycholic Acid Therapy in Patients with Primary Biliary Cholangitis with
Limited Liver Transplantation Availability.
AB - INTRODUCTION: There is little information on survival rates of patients with
primary biliary cholangtis (PBC) in developing countries. This is particularly
true in Latin America, where the number of liver transplants performed remains
extremely low for patients with advanced liver disease who fulfill criteria for
liver transplantation. The goal of this study was to compare survival rate of
patients with PBC in developing countries who were treated with ursodeoxycholic
acid (UDCA) versus survival of patients who received other treatments (OT)
without UDCA, prescribed before the UDCA era. MATERIAL AND METHODS: A
retrospective study was performed, including records of 78 patients with PBC in
the liver unit in a third level referral hospital in Mexico City. Patients were
followed for five years from initial diagnosis until death related to liver
disease or to the end of the study. Patients received UDCA (15 mg/kg/per day) (n
= 41) or OT (n = 37) before introduction of UDCA in Mexico. RESULTS: Response to
treatment was higher in the group that received UDCA. In the five years of follow
up, survival rates were significantly higher in the UDCA group than in the OT
group. The hazard ratio of death was higher in the OT group vs. UDCA group, HR
8.78 (95% CI, 2.52-30.61); Mayo Risk Score and gender were independently
associated with the risk of death. CONCLUSIONS: The study confirms that the use
of UDCA in countries with a limited liver transplant program increases survival
in comparison to other treatments used before the introduction of UDCA.
PMID- 28425414
TI - Cholangiohydatidosis: an Infrequent Cause of Obstructive Jaundice and Acute
Cholangitis.
AB - BACKGROUND: One of the evolutionary complications of hepatic echinococcosis (HE)
is cholangiohydatidosis, a rare cause of obstructive jaundice and cholangitis.
The aim of this study was to describe the results of surgical treatment on a
group of patients with cholangiohydatidosis and secondary cholangitis in terms of
post-operative morbidity (POM). MATERIAL AND METHOD: Case series of patients
operated on for cholangiohydatidosis and cholangitis in the Department at Surgery
of the Universidad de La Frontera and the Clinica Mayor in Temuco, Chile between
2004 and 2014. The minimum follow-up time was six months. The principal outcome
variable was the development of POM. Other variables of interest were age, sex,
cyst diameter, hematocrit, leukocytes, total bilirubin, alkaline phosphatase and
transaminases, type of surgery, existence of concomitant evolutionary
complications in the cyst, length of hospital stay, need for surgical re
intervention and mortality. Descriptive statistics were calculated. RESULTS: A
total of 20 patients were studied characterized by a median age of 53 years,
50.0% female and 20.0% having two or more cysts with a mean diameter of 13.3 +/-
6.3 cm. A median hospital stay of six days and follow-up of 34 months was
recorded. POM was 30.0%, re-intervention rate was 10.0% and mortality rate was
5.0%. CONCLUSION: Cholangiohydatidosis is a rare cause of obstructive jaundice
and cholangitis associated with significant rates of POM and mortality.
PMID- 28425415
TI - Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical
Features and Predictors of Mortality.
AB - INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is
one of the important causes of acute liver failure which results in significant
morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were
enrolled based on predefined criteria and followed up for at least 6 months or
until normalization of liver tests. Causality assessment was done by applying the
Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from
82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41
men; median age, 38 years). The most commonly implicated drugs were
antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and
alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal
anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver
related mortality was significantly higher for ATT DILI (17.5%) vs. those without
(2.4%) (P = 0.02). There was no significant difference in overall as well as
liver related mortality in hepatocellular, cholestatic or mixed pattern of
injury. Laboratory parameters at one week after discontinuation of drug predicted
mortality better than those at the time of DILI recognition. On multivariate
logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage
liver disease) score and alkaline phosphatase at one week, independently
predicted mortality. CONCLUSION: DILI results in significant overall mortality
(15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading
causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and
alkaline phosphatase at one week are independent predictors of mortality.
PMID- 28425416
TI - GNPAT rs11558492 is not a Major Modifier of Iron Status: Study of Italian
Hemochromatosis Patients and Blood Donors.
AB - BACKGROUND AND AIM: HFE-related Hemochromatosis (HH) is characterized by marked
phenotype heterogeneity, probably due to the combined action of acquired and
genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of
iron status, but results are still controversial. To shed light on these
discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy
controls. MATERIAL AND METHODS: Allele and genotype frequencies were analysed and
compared with those reported in Exome Variant Server (EVS). To explore the role
of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver
iron concentration (LIC) and iron removed (IR) were studied according to allele
and genotype frequencies. In addition, the effect of the SNP on liver fibrosis
was examined comparing patients with absent/mild-moderate fibrosis to those with
severe fibrosis-cirrhosis. RESULTS: GNPAT rs11558492 minor allele (G) frequency
(MAF) was 20.3% in HFE-HH, 17.2% in controls and 20.6% in EVS database. Genotype
frequencies were 64% and 69.2% (AA), 31.2% and 27.2% (AG), 4.8% and 3.6% (GG) in
HFE-HH and controls, respectively. No significant differences were found
comparing genotype and allele frequencies even selecting subgroups of only-males
with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not
significantly differ according to rs11558492 genotypes. Also, MAF did not differ
between patients with absent/mild fibrosis and severe fibrosis/cirrhosis.
CONCLUSIONS: Our findings indicate that GNPAT rs11558492 is not a major modifier
of iron status and is not associated with liver fibrosis in HFE-HH patients.
PMID- 28425417
TI - Spontaneous Resolution of Multiple Hepatic Masses: Hepatic Inflammatory
Pseuduotumor.
PMID- 28425418
TI - Recurrent Hyperammonemia After Abernethy Malformation Type 2 Closure: a Case
Report.
AB - The Abernethy malformation is a rare congenital malformation defined by the
presence of an extrahepatic portosystemic shunt. Although most patients are
asymptomatic, clinical encephalopathy is present in 15% of cases. We present a
patient with type 2 Abernethy malformation, hyperammonemia, and encephalopathy.
Shunt closure was performed successfully using interventional angiography;
however, hyperammonemia recurred 3 months later. The diagnosis of Abernethy
malformation can be made easily, but the ideal patient management strategy has
not yet been established. This is the first reported patient with recurrence of
hyperammonemia after interventional treatment; we discuss the therapeutic options
for Abernethy malformation.
PMID- 28425419
TI - A Rare BSEP Mutation Associated with a Mild Form of Progressive Familial
Intrahepatic Cholestasis Type 2.
AB - Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2) is a rare
cholestatic disorder diagnosed in infancy or childhood that can lead to severe
hepatic fibrosis and liver failure. Mutations in the ABCB11 gene result in a
deficiency of the bile salt export protein (BSEP) and accumulation of bile inside
the hepatocytes. Hepatocellular carcinoma is another condition associated with
severe forms of deletion mutations in the ABCB11 gene. Treatment options
including ursodeoxycholic acid biliary diversion have mixed outcomes and some
patients require liver transplantation. Here, we describe two siblings with an
extremely mild form of PFIC2 inherited from heterozygous parents. The elder
sibling had acute liver failure at the age of six months and both siblings had
pruritus, cholestasis, coagulopathy and fat-soluble-vitamin deficiencies in
infancy but have been asymptomatic past infancy. Genetic testing of the siblings
revealed that each were compound heterozygotes for two missense mutations of the
ABCB11 gene: p.C68Y and p.R832H. Medical treatment typical for PFIC2 has not been
necessary for either patient. This is the first report of these variants
following a mild course in two affected patients.
PMID- 28425420
TI - HbA1c Levels as a Parameter of Glycemic Control in Patients with Liver Diseases.
PMID- 28425421
TI - Reply to "HbA1c levels as a parameter of glycemic control in patients with liver
cirrhosis".
PMID- 28425422
TI - Mass mortality of eastern box turtles with upper respiratory disease following
atypical cold weather.
AB - Emerging infectious diseases cause population declines in many ectotherms, with
outbreaks frequently punctuated by periods of mass mortality. It remains unclear,
however, whether thermoregulation by ectotherms and variation in environmental
temperature is associated with mortality risk and disease progression, especially
in wild populations. Here, we examined environmental and body temperatures of
free-ranging eastern box turtles Terrapene carolina during a mass die-off
coincident with upper respiratory disease. We recorded deaths of 17 turtles that
showed clinical signs of upper respiratory disease among 76 adult turtles
encountered in Berea, Kentucky (USA), in 2014. Of the 17 mortalities, 11 occurred
approximately 14 d after mean environmental temperature dropped 2.5 SD below the
3 mo mean. Partial genomic sequencing of the major capsid protein from 1 sick
turtle identified a ranavirus isolate similar to frog virus 3. Turtles that
lacked clinical signs of disease had significantly higher body temperatures (23
degrees C) than sick turtles (21 degrees C) during the mass mortality, but sick
turtles that survived and recovered eventually warmed (measured by temperature
loggers). Finally, there was a significant negative effect of daily environmental
temperature deviation from the 3 mo mean on survival, suggesting that rapid
decreases in environmental temperature were correlated with mortality. Our
results point to a potential role for environmental temperature variation and
body temperature in disease progression and mortality risk of eastern box turtles
affected by upper respiratory disease. Given our findings, it is possible that
colder or more variable environmental temperatures and an inability to
effectively thermoregulate are associated with poorer disease outcomes in eastern
box turtles.
PMID- 28425423
TI - Pathology and molecular analysis of Hapalotrema mistroides (Digenea:
Spirorchiidae) infecting a Mediterranean loggerhead turtle Caretta caretta.
AB - Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a
major threat for sea turtle health and are considered the most important
parasitic cause of turtle stranding and mortality worldwide. Despite the large
diversity of spirorchiid species found globally, there are only 2 records for
free-ranging Mediterranean sea turtles that date back to the late 1800s involving
just Hapalotrema mistroides Monticelli, 1896. This study describes the first
fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean
loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of
taxonomic identification of these parasites, provides the first molecular
characterization and phylogenetic analysis of H. mistroides from the
Mediterranean Sea. The loggerhead turtle showed cachexia and digestive disorders
associated with severe damage to the pancreas and intestinal ganglia, caused by
deposition of Hapalotrema eggs forming granulomas. Massive Hapalotrema egg emboli
in several tissues and organs and encephalitis were the most probable
contributions to the death of the turtle. The congruence between the phylogenetic
analysis of both the ITS2 and 28S rDNA resolved the Italian and USA H. mistroides
as the same species, confirming the parasite identification. The case here
described clearly indicates that the blood flukes should be considered in the
differential diagnosis of Mediterranean sea turtle diseases.
PMID- 28425424
TI - Spatial distribution of Batrachochytrium dendrobatidis in South American
caecilians.
AB - The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) is linked to
population declines in anurans and salamanders globally. To date, however, few
studies have attempted to screen Bd in live caecilians; Bd-positive caecilians
have only been reported in Africa and French Guiana. Here, we performed a
retrospective survey of museum preserved specimens to (1) describe spatial
patterns of Bd infection in Gymnophiona across South America and (2) test whether
areas of low climatic suitability for Bd in anurans predict Bd spatial
epidemiology in caecilians. We used quantitative PCR to detect Bd in preserved
caecilians collected over a 109 yr period, and performed autologistic regressions
to test the effect of bioclimatic metrics of temperature and precipitation,
vegetation density, and elevation on the likelihood of Bd occurrence. We detected
an overall Bd prevalence of 12.4%, with positive samples spanning the Uruguayan
savanna, Brazil's Atlantic Forest, and the Amazon basin. Our autologistic models
detected a strong effect of macroclimate, a weaker effect of vegetation density,
and no effect of elevation on the likelihood of Bd occurrence. Although most of
our Bd-positive records overlapped with reported areas of high climatic
suitability for the fungus in the Neotropics, many of our new Bd-positive samples
extend far into areas of poor suitability for Bd in anurans. Our results
highlight an important gap in the study of amphibian chytridiomycosis: the
potential negative impact of Bd on Neotropical caecilians and the hypothetical
role of caecilians as Bd reservoirs.
PMID- 28425425
TI - Skeletal anomalies in reared Senegalese sole Solea senegalensis juveniles: a
radiographic approach.
AB - Reared Senegalese sole Solea senegalensis Kaup show a high incidence of vertebral
anomalies; however, little is known about its skeletal anomaly profile in the
later farming phases. The purpose of this study was to provide a detailed
description and quantification of the most common skeletal anomalies in reared
Senegalese sole in the juvenile stage by means of computed radiography. A total
of 374 Senegalese sole were classified according to the external morphology of
the fish as normal or altered and then radiographed in latero-lateral and in
dorso-ventral projections. Radiographic evaluation of anomalies focused
especially on vertebral body anomalies (VBA) and vertebral column deviations
(VCD). The 2 orthogonal projections provided a more complete visualization of the
skeleton. Approximately 75% of the individuals showed at least 1 anomaly, while
VBA and/or VCD were detected in 48.9% of the specimens. Regarding external
morphology, 88% of the fish were categorized as normal, although about 72% of
these normal fish displayed abnormalities in radiographies. The most frequent
anomalies consisted of deformations of the caudal complex plates (hypurals,
parhypural and epural), preurals and caudal vertebrae. Scoliosis was the most
prevalent among VCD, affecting the caudal area in almost 15% of the individuals.
The anomaly profile at the juvenile stages showed some differences compared to
what has been reported previously in earlier stages of development. In light of
these results, further investigation into the progression of skeletal anomalies
over time and the causative factors at later stages is required.
PMID- 28425426
TI - Production of red tilapia (Oreochromis spp.) in floating cages in the Mekong
Delta, Vietnam: mortality and health management.
AB - The Mekong Delta in Vietnam is one of the most productive aquaculture regions in
the world, in which the red tilapia (Oreochromis spp.) industry is a small-scale
industry that mainly supplies local markets in the delta region. Little is known
about the frequency of mortality events and health management in this sector. We
describe red tilapia floating cage production systems in the Mekong Delta,
Vietnam, for the purposes of quantifying mortality and associated production
factors, and describing practices that may influence pathogen introduction and
spread to and from farms. In July 2014, approximately 50 red tilapia farmers from
4 provinces (201 farmers in total) were randomly selected and interviewed. Median
overall perceived mortality (PM) within a production cycle was 35%. Overall PM
was found to be affected by province (p < 0.01), age of farmers (p = 0.01),
anticipated main reason for PM in the first 2 wk (p = 0.03), most common market
for the fish (p = 0.02), and whether farmers recorded stocking information (p =
0.01). Based on the interviews, we describe and discuss processes that
potentially affect pathogen introduction and spread on these farms, such as
movements of live and dead fish, distances between farms, mechanical
transmission, and biosecurity practices such as treating fish before stocking,
using disinfectants, and sharing equipment, and harvesters' movements. This study
provides fundamental understanding of red tilapia aquaculture management in the
Mekong Delta, and describes management factors that could become important in the
event of disease outbreaks.
PMID- 28425427
TI - Tetracapsuloides bryosalmonae abundance in river water.
AB - Tetracapsuloides bryosalmonae is a myxozoan parasite of freshwater bryozoans and
salmonids, causing proliferative kidney disease in the latter. To date, detection
of the parasite has required collection of hosts and subsequent molecular or
histological examination. The release of infectious spores from both hosts offers
an opportunity to detect the parasite in water samples. We developed a novel
SYBR(r) Green quantitative real-time PCR (qPCR) assay for T. bryosalmonae in
water samples which provides an estimation of bryozoan malacospore numbers and
tested the assay in 3 rivers in southern England (UK) over a period of 5 wk. The
assay proved to be both highly sensitive and specific to the parasite, detecting
low levels of spores throughout the study period. Larger-volume samples afforded
greater detection likelihood, but did not increase the number of spores detected,
possibly as a result of low and patchy spore distributions and lack of within
site replication of large-volume samples. Based on point-measurements,
temperature was positively associated with the likelihood of detecting spores,
possibly reflecting the temperature dependence of spore shedding from bryozoan
hosts. The presence of T. bryosalmonae in water samples was predominantly
influenced by spatial (sites within rivers, amongst rivers) and temporal
(sampling dates) factors, while the latter also influenced quantification cycle
(Cq) values and spore abundance. Environmental monitoring for infectious stages
can complement traditional methods, providing faster and easier detection and
avoiding potentially prolonged searching, collecting and destructive sampling of
invertebrate and vertebrate hosts.
PMID- 28425428
TI - Innate immune response of channel catfish Ictalurus punctatus mannose-binding
lectin to channel catfish virus (CCV).
AB - The channel catfish virus (CCV) is a pathogenic herpesvirus that infects channel
catfish Ictalurus punctatus in pond aquaculture in the southeastern USA. Mannose
binding lectin (MBL), an innate immune protein, could play an important role in
the innate response of channel catfish by binding to CCV. Cell cultures of CCV
were grown in channel catfish ovary cells (CCOC). A dot-immunoblot enzyme-linked
immunosorbent assay was done to determine the binding ability of 5 mo old channel
catfish serum MBL (26.2 ug ml-1) to CCOC infected with CCV. Two separate
nitrocellulose membrane blotting techniques were done using uninfected and
infected CCOC. The uninfected CCOC decreased by 29.3 and 33.4% in their binding
of channel catfish MBL when compared with infected CCOC using the 2 membrane
procedures. The combined average binding ability of channel catfish MBL towards
infected CCOC was therefore 31.4% greater when comparing the infected and
uninfected CCOC. Normalization equation values of MBL for the 5 mo old catfish
were compared for the 2 membrane binding procedures. The 2 normalization values
were very close (142 and 150) in binding ability of MBL to the infected CCOC. The
5 mo catfish serum had twice the concentration of MBL (26.2 ug ml-1) compared to
7 mo catfish serum (13.2 ug ml-1), and the binding percentage of 5 mo serum was
2.4 times greater in infected than in uninfected cells. This demonstrates that
the binding of channel catfish serum MBL to CCV is concentration dependent and is
related to serum concentrations of MBL.
PMID- 28425429
TI - Evidence of horizontal transmission of the cancer-associated Steamer
retrotransposon among ecological cohort bivalve species.
AB - Bivalve specimens from legacy frozen tissue collections, and others freshly
obtained, were surveyed for the presence of the Steamer long terminal repeat
(LTR)-retrotransposon associated with disseminated hemic neoplasia of the soft
shelled clam Mya areneria. Of 22 species investigated using primers for the pol
region, only Atlantic M. arenaria, Atlantic and North Sea razor clams Ensis
directus, and Baltic clams Macoma balthica from the North Sea were found to
possess copies of Steamer in their genomes. Notably, close relatives like Mya
truncata and Siliqua patula did not exhibit evidence of Steamer. Amplified
Steamer sequences were uniformly identical in all M. areneria specimens, and were
highly variable across specimens of E. directus. Variation in the latter included
nucleotide polymorphisms among and within individuals as well as length variation
in 2 specimens corresponding to the deletion of a predicted stable hairpin
structure. Results implicate Atlantic razor clams as the proximal source for
horizontal transmission of Steamer among ecologically similar yet markedly
distantly related bivalves. The consequences of cross-species transmission of the
Steamer retrotransposon are unknown, and the finding of Steamer in 3 bivalve
species suggests that further spread is possible.
PMID- 28425430
TI - Dose assessment from chronic exposure to industrial NORM in iron ore processing.
AB - Radiological exposures due to naturally occurring radioactive material (NORM) can
occur during a wide range of work-related activities in the mineral processing
and chemical industries. However, evaluation of such exposures in industrial
settings remains a difficult exercise owing inter alia to the large number of
personnel, operations and plants affected; assumptions that often have to be made
concerning the actual duration and frequency of exposures; the complex chemistry
and radioactive disequilibria involved and typically, the paucity of historical
data. In our study, the challenges associated with assessing chronic exposure to
fugitive dust enriched in 210Pb and 210Po and the determination of the associated
internal dose by inhalation and ingestion are described by reference to a case
study undertaken at an iron ore sintering plant between June 2013 and July 2015.
The applicability of default dose coefficients and biokinetic models provided by
the International Commission for Radiological Protection was verified by
combining air and dust monitoring with information on the characteristics of the
aerosols and in-vitro solubility experiments. The disparity between particulate
matter 100 microns or less in diameter (PM100), particulate matter 10 microns or
less in diameter (PM10) and 210Pb/210Po activity concentrations observed over the
different monitoring campaigns and sampling locations confirmed that use
positional short-term monitoring surveys to extrapolate intake over a year was
not appropriate and could lead to unrealistic intake and dose figures. Personal
air sampling is more appropriate for estimating the dose in such situations,
though it is not always practical and may collect insufficient quantities of
material for radiochemical analysis; this is an important constraint when dealing
with low specific activity materials.
PMID- 28425431
TI - Characterization of spatial distortion in a 0.35 T MRI-guided radiotherapy
system.
AB - Spatial distortion results in image deformation that can degrade accurate
targeting and dose calculations in MRI-guided adaptive radiotherapy. The authors
present a comprehensive assessment of a 0.35 T MRI-guided radiotherapy system's
spatial distortion using two commercially-available phantoms with regularly
spaced markers. Images of the spatial integrity phantoms were acquired using five
clinical protocols on the MRI-guided radiotherapy machine with the radiotherapy
gantry positioned at various angles. Software was developed to identify and
localize all phantom markers using a template matching approach. Rotational and
translational corrections were implemented to account for imperfect phantom
alignment. Measurements were made to assess uncertainties arising from
susceptibility artifacts, image noise, and phantom construction accuracy. For a
clinical 3D imaging protocol with a 1.5 mm reconstructed slice thickness, 100% of
spheres within a 50 mm radius of isocenter had a 3D deviation of 1 mm or less. Of
the spheres within 100 mm of isocenter, 99.9% had a 3D deviation less than 1 mm.
94.8% and 100% of the spheres within 175 mm were found to be within 1 mm and 2 mm
of the expected positions in 3D respectively. Maximum 3D distortions within 50
mm, 100 mm and 175 mm of isocenter were 0.76 mm, 1.15 mm and 1.88 mm
respectively. Distortions present in images acquired using the real-time imaging
sequence were less than 1 mm for 98.1% and 95.0% of the cylinders within 50 mm
and 100 mm of isocenter. The corresponding maximum distortion in these regions
was 1.10 mm and 1.67 mm. These results may be used to inform appropriate planning
target volume (PTV) margins for 0.35 T MRI-guided radiotherapy. Observed levels
of spatial distortion should be explicitly considered when using PTV margins of 3
mm or less or in the case of targets displaced from isocenter by more than 50 mm.
PMID- 28425432
TI - Angiogenic and lymphangiogenic profiles in histological variants of papillary
thyroid carcinoma.
AB - INTRODUCTION: Papillary thyroid carcinoma (PTC) is a well-differentiated tumor
that occurs in several histological variants whose biological behaviors remain
unclear. Angiogenesis and lymphangiogenesis are critical processes that enable
tumor progression. OBJECTIVES: The aim of this study was to evaluate the
angiogenic and lymphangiogenic phenotypes of PTC, considering the differences
between histological variants. PATIENTS AND METHODS: Angiogenic and
lymphangiogenic profiles were analyzed by determining microvascular density (MVD)
and lymphatic vessel density (LVD) in 73 cases of PTC, using
immunohistochemistry. To assess the biological markers involved in blood and
lymph vessel formation, the expression of vascular endothelial growth factor
(VEGF), cyclooxygenase 2 (COX-2), and p27kip1 (p27) was determined. RESULTS: MVD
was significantly higher in patients with high-risk PTC and in those with local
extrathyroidal and vascular invasion. Positive VEGF expression was strongly
associated with high MVD and age-related tumor enlargement. The presence of lymph
vessel invasion was associated with the expression of either VEGF or COX-2. The
analysis of angiogenesis and lymphangiogenesis in different histological variants
of PTC revealed elevated LVD rather than MVD in the follicular variant of PTC (FV
PTC).Lower MVD was observed in FV-PTC relative to the classic variant of PTC (CV
PTC). The frequency of VEGF-positive tumors was higher in CV-PTC than in FV-PTC.
A significant association between COX-2 and p27 expression was observed in FV-PTC
but not in CV-PTC. CONCLUSIONS: These results suggest that VEGF, COX-2, and p27
may be important biological markers that determine the angiogenic and
lymphangiogenic potentials of PTC, particularly between the follicular and
classic variants.
PMID- 28425434
TI - Corrigendum: Coherent creation and destruction of orbital wavepackets in Si:P
with electrical and optical read-out.
PMID- 28425433
TI - Prior context in audition informs binding and shapes simple features.
AB - A perceptual phenomenon is reported, whereby prior acoustic context has a large,
rapid and long-lasting effect on a basic auditory judgement. Pairs of tones were
devised to include ambiguous transitions between frequency components, such that
listeners were equally likely to report an upward or downward 'pitch' shift
between tones. We show that presenting context tones before the ambiguous pair
almost fully determines the perceived direction of shift. The context effect
generalizes to a wide range of temporal and spectral scales, encompassing the
characteristics of most realistic auditory scenes. Magnetoencephalographic
recordings show that a relative reduction in neural responsivity is correlated to
the behavioural effect. Finally, a computational model reproduces behavioural
results, by implementing a simple constraint of continuity for binding successive
sounds in a probabilistic manner. Contextual processing, mediated by ubiquitous
neural mechanisms such as adaptation, may be crucial to track complex sound
sources over time.
PMID- 28425436
TI - Corrigendum: MHC-dependent inhibition of uterine NK cells impedes fetal growth
and decidual vascular remodeling.
PMID- 28425435
TI - FRET biosensor uncovers cAMP nano-domains at beta-adrenergic targets that dictate
precise tuning of cardiac contractility.
AB - Compartmentalized cAMP/PKA signalling is now recognized as important for
physiology and pathophysiology, yet a detailed understanding of the properties,
regulation and function of local cAMP/PKA signals is lacking. Here we present a
fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects
compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific
multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and
myofilament sites, reveals differential kinetics and amplitudes of localized cAMP
signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize
cardiac contractility upon adrenergic activation. At low adrenergic levels, and
those mimicking heart failure, differential local cAMP responses are exacerbated,
with near abolition of cAMP signalling at certain locations. This work provides
tools and fundamental mechanistic insights into subcellular adrenergic signalling
in normal and pathological cardiac function.
PMID- 28425437
TI - Are genetic polymorphisms in the renin-angiotensin-aldosterone system associated
with essential hypertension? Evidence from genome-wide association studies.
AB - In candidate gene era, dozens of single-nucleotide polymorphisms (SNPs) within
renin-angiotensin-aldosterone system (RAAS) have been reported to be
significantly associated with hypertension. However, the unbiased genome-wide
association studies (GWAS) rarely identified the SNPs within RAAS were associated
with hypertension or blood pressure (BP) traits. In order to figure out whether
genetic polymorphisms of RAAS are really associated with hypertension, we
systemically searched the GWAS Catalogue and identified all the known RAAS genes
and relevant diseases/traits. After data processing, we found that polymorphisms
within REN, AGT, ACE2, CYP11B2, ATP6AP2 and HSD11B2 were not associated with any
disease or trait. SNPs within ACE, AGTR1, AGTR2, MAS1, RENBP and NR3C2 were
associated with other diseases or traits, but showed no direct connection with
hypertension. The only SNP associated with a BP trait, systolic BP was
rs17367504. However, it is located in the intronic region of MTHFR near many
plausible candidate genes, including CLCN6, NPPA, NPPB and AGTRAP. Therefore, the
effect of RAAS polymorphisms may have been overestimated during the 'candidate
gene era'. In the time of 'precision medicine', the power of RAAS variants needs
to be reconsidered when evaluating one's susceptibility of hypertension.
PMID- 28425438
TI - Mitochondrial DNA copy number in peripheral blood cell and hypertension risk
among mining workers: a case-control study in Chinese coal miners.
AB - Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant
induced cell damage, has been observed in a wide range of human diseases.
However, whether it correlates with hypertension has not been elucidated. We
aimed to explore the association between mtDNA copy number and the risk of
hypertension in Chinese coal miners. A case-control study was performed with 378
hypertension patients and 325 healthy controls in a large coal mining group
located in North China. Face-to-face interviews were conducted by trained staffs
with necessary medical knowledge. The mtDNA copy number was measured by a
quantitative real-time PCR assay using DNA extracted from peripheral blood. No
significant differences in mtDNA copy number were observed between hypertension
patients and healthy controls. However, in both case and control groups, the
mtDNA copy number was statistically significantly lower in the elder population
(>=45 years old) compared with the younger subjects (<45 years old; 7.17 vs 6.64,
P=0.005 and 7.21 vs 6.84, P=0.036). A significantly higher mtDNA copy number
could be found in hypertension patients consuming alcohol regularly compared with
no alcohol consumption patients (7.09 vs 6.69); mtDNA copy number was also
positively correlated with age and alcohol consumption. Hypertension was found
significantly correlated with factors such as age, work duration, monthly family
income and drinking status. Our results suggest that the mtDNA copy number is not
associated with hypertension in coal miners.
PMID- 28425439
TI - Activation of the hypothalamic feeding centre upon visual prey detection.
AB - The visual system plays a major role in food/prey recognition in diurnal animals,
and food intake is regulated by the hypothalamus. However, whether and how visual
information about prey is conveyed to the hypothalamic feeding centre is largely
unknown. Here we perform real-time imaging of neuronal activity in freely
behaving or constrained zebrafish larvae and demonstrate that prey or prey-like
visual stimuli activate the hypothalamic feeding centre. Furthermore, we identify
prey detector neurons in the pretectal area that project to the hypothalamic
feeding centre. Ablation of the pretectum completely abolishes prey capture
behaviour and neurotoxin expression in the hypothalamic area also reduces
feeding. Taken together, these results suggest that the pretecto-hypothalamic
pathway plays a crucial role in conveying visual information to the feeding
centre. Thus, this pathway possibly converts visual food detection into feeding
motivation in zebrafish.
PMID- 28425441
TI - Methyl parathion detection in vegetables and fruits using silver@graphene
nanoribbons nanocomposite modified screen printed electrode.
AB - We have developed a sensitive electrochemical sensor for Organophosphorus
pesticide methyl parathion (MP) using silver particles supported graphene
nanoribbons (Ag@GNRs). The Ag@GNRs nanocomposite was prepared through facile wet
chemical strategy and characterized by TEM, EDX, XRD, Raman, UV-visible,
electrochemical and impedance spectroscopies. The Ag@GNRs film modified screen
printed carbon electrode (SPCE) delivers excellent electrocatalytic ability to
the reduction of MP. The Ag@GNRs/SPCE detects sub-nanomolar concentrations of MP
with excellent selectivity. The synergic effects between special electrocatalytic
ability of Ag and excellent physicochemical properties of GNRs (large surface
area, high conductivity, high area-normalized edge-plane structures and abundant
catalytic sites) make the composite highly suitable for MP sensing. Most
importantly, the method is successfully demonstrated in vegetables and fruits
which revealed its potential real-time applicability in food analysis.
PMID- 28425440
TI - The valosin-containing protein is a novel mediator of mitochondrial respiration
and cell survival in the heart in vivo.
AB - The valosin-containing protein (VCP) participates in signaling pathways essential
for cell homeostasis in multiple tissues, however, its function in the heart in
vivo remains unknown. Here we offer the first description of the expression,
function and mechanism of action of VCP in the mammalian heart in vivo in both
normal and stress conditions. By using a transgenic (TG) mouse with cardiac
specific overexpression (3.5-fold) of VCP, we demonstrate that VCP is a new and
powerful mediator of cardiac protection against cell death in vivo, as evidenced
by a 50% reduction of infarct size after ischemia/reperfusion versus wild type.
We also identify a novel role of VCP in preserving mitochondrial respiration and
in preventing the opening of mitochondrial permeability transition pore in
cardiac myocytes under stress. In particular, by genetic deletion of inducible
isoform of nitric oxide synthase (iNOS) from VCP TG mouse and by pharmacological
inhibition of iNOS in isolated cardiac myocytes, we reveal that an increase of
expression and activity of iNOS in cardiomyocytes by VCP is an essential
mechanistic link of VCP-mediated preservation of mitochondrial function. These
data together demonstrate that VCP may represent a novel therapeutic avenue for
the prevention of myocardial ischemia.
PMID- 28425442
TI - Hierarchical Decomposition for Betweenness Centrality Measure of Complex
Networks.
AB - Betweenness centrality is an indicator of a node's centrality in a network. It is
equal to the number of shortest paths from all vertices to all others that pass
through that node. Most of real-world large networks display a hierarchical
community structure, and their betweenness computation possesses rather high
complexity. Here we propose a new hierarchical decomposition approach to speed up
the betweenness computation of complex networks. The advantage of this new method
is its effective utilization of the local structural information from the
hierarchical community. The presented method can significantly speed up the
betweenness calculation. This improvement is much more evident in those networks
with numerous homogeneous communities. Furthermore, the proposed method features
a parallel structure, which is very suitable for parallel computation. Moreover,
only a small amount of additional computation is required by our method, when
small changes in the network structure are restricted to some local communities.
The effectiveness of the proposed method is validated via the examples of two
real-world power grids and one artificial network, which demonstrates that the
performance of the proposed method is superior to that of the traditional method.
PMID- 28425443
TI - Hybridization of Strength Pareto Multiobjective Optimization with Modified Cuckoo
Search Algorithm for Rectangular Array.
AB - This research proposes the various versions of modified cuckoo search (MCS)
metaheuristic algorithm deploying the strength Pareto evolutionary algorithm
(SPEA) multiobjective (MO) optimization technique in rectangular array geometry
synthesis. Precisely, the MCS algorithm is proposed by incorporating the Roulette
wheel selection operator to choose the initial host nests (individuals) that give
better results, adaptive inertia weight to control the positions exploration of
the potential best host nests (solutions), and dynamic discovery rate to manage
the fraction probability of finding the best host nests in 3-dimensional search
space. In addition, the MCS algorithm is hybridized with the particle swarm
optimization (PSO) and hill climbing (HC) stochastic techniques along with the
standard strength Pareto evolutionary algorithm (SPEA) forming the MCSPSOSPEA and
MCSHCSPEA, respectively. All the proposed MCS-based algorithms are examined to
perform MO optimization on Zitzler-Deb-Thiele's (ZDT's) test functions. Pareto
optimum trade-offs are done to generate a set of three non-dominated solutions,
which are locations, excitation amplitudes, and excitation phases of array
elements, respectively. Overall, simulations demonstrates that the proposed
MCSPSOSPEA outperforms other compatible competitors, in gaining a high antenna
directivity, small half-power beamwidth (HPBW), low average side lobe level (SLL)
suppression, and/or significant predefined nulls mitigation, simultaneously.
PMID- 28425444
TI - Model potential for the description of metal/organic interface states.
AB - We present an analytical one-dimensional model potential for the description of
electronic interface states that form at the interface between a metal surface
and flat-lying adlayers of pi-conjugated organic molecules. The model utilizes
graphene as a universal representation of these organic adlayers. It predicts the
energy position of the interface state as well as the overlap of its wave
function with the bulk metal without free fitting parameters. We show that the
energy of the interface state depends systematically on the bond distance between
the carbon backbone of the adayers and the metal. The general applicability and
robustness of the model is demonstrated by a comparison of the calculated
energies with numerous experimental results for a number of flat-lying organic
molecules on different closed-packed metal surfaces that cover a large range of
bond distances.
PMID- 28425445
TI - Scenario dependence of future changes in climate extremes under 1.5 degrees C
and 2 degrees C global warming.
AB - The 2015 Paris Agreement aims to limit global warming below 2 degrees C and
pursue efforts to even limit it to 1.5 degrees C relative to pre-industrial
levels. Decision makers need reliable information on the impacts caused by these
warming levels for climate mitigation and adaptation measures. We explore the
changes in climate extremes, which are closely tied to economic losses and
casualties, under 1.5 degrees C and 2 degrees C global warming and their
scenario dependence using three sets of ensemble global climate model
simulations. A warming of 0.5 degrees C (from 1.5 degrees C to 2 degrees C)
leads to significant increases in temperature and precipitation extremes in most
regions. However, the projected changes in climate extremes under both warming
levels highly depend on the pathways of emissions scenarios, with different
greenhouse gas (GHG)/aerosol forcing ratio and GHG levels. Moreover, there are
multifold differences in several heavily polluted regions, among the scenarios,
in the changes in precipitation extremes due to an additional 0.5 degrees C
warming from 1.5 degrees C to 2 degrees C. Our results demonstrate that the
chemical compositions of emissions scenarios, not just the total radiative
forcing and resultant warming level, must be considered when assessing the
impacts of global 1.5/2 degrees C warming.
PMID- 28425446
TI - YAP modulates TGF-beta1-induced simultaneous apoptosis and EMT through
upregulation of the EGF receptor.
AB - YAP is a transcriptional co-regulator that plays important roles in various patho
physiological processes, including the survival and death of cells. However, the
effect of YAP on apoptosis and EMT, simultaneously mediated by TGF-beta1, is not
known. In this study, we demonstrate that YAP can modulate cell fate of apoptosis
versus EMT by acting as a surviving factor. Overexpression of YAP in mouse
mammary epithelial (NMuMG) cells suppressed TGF-beta1-induced apoptosis, which
shifted the cellular response predominantly toward EMT. In contrast, knockdown of
YAP induced spontaneous apoptosis and enhanced TGF-beta1-induced apoptosis,
leading to a sharp decrease in the proportion of surviving cells that underwent
EMT. These data suggest that YAP is an essential factor for modulating cellular
responses to TGF-beta1. Further investigation showed that YAP could regulate the
expression level and activation of EGFR. Knockdown or inhibition of EGFR
abolished the suppressive effect of YAP on apoptosis, whereas activation of EGFR
by EGF significantly reduced apoptosis caused by the knockdown of YAP. The
results indicate that EGFR and its activation are critical for YAP-mediated
suppression of TGF-beta1-induced apoptosis. This study provides a new
understanding of the regulatory mechanism underlying the determination of cell
fate in response to TGF-beta1-mediated simultaneous apoptosis and EMT.
PMID- 28425448
TI - Corrigendum: Visualization of Neuregulin 1 ectodomain shedding reveals its local
processing in vitro and in vivo.
PMID- 28425447
TI - Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein
Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal
Model.
AB - : Recombinant human myelin basic protein (rhMBP) was previously produced in the
milk of transgenic cows. Differences in molecular recognition of either hMBP or
rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This
indicated differences in immunological response between rhMBP and hMBP. Here, the
activity of free and controlled release rhMBP poly(epsilon-caprolactone)
nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was
demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model.
Following optimization of nanoformulation, discrete spherical, rough-surfaced
rhMBP NPs with high entrapment efficiency and controlled release pattern were
obtained. Results indicated that rhMBP was loaded into and electrostatically
adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP
NPs before EAE-induction reduced the average behavioral score in EAE mice and
showed only mild histological alterations and preservation of myelin sheath, with
rhMBP NPs showing increased protection. Moreover, analysis of inflammatory
cytokines (IFN-gamma and IL-10) in mice brains revealed that pretreatment with
free or rhMBP NPs significantly protected against induced inflammation. IN
CONCLUSION: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii)
nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine
and iii) clinical investigations are required to demonstrate the activity of
rhMBP NPs as a therapeutic vaccine for MS.
PMID- 28425449
TI - The Impact of Treatments for Depression on the Dynamic Network Structure of
Mental States: Two Randomized Controlled Trials.
AB - Evidence is growing that vulnerability to depression may be characterized by
strong negative feedback loops between mental states. It is unknown whether such
dynamics between mental states can be altered by treatment. This study examined
whether treatment with imipramine or treatment with Mindfulness-Based Cognitive
Therapy (MBCT) reduces the connectivity within dynamic networks of mental states
in individuals with depressive symptoms. In the Imipramine trial, individuals
diagnosed with major depression were randomized to imipramine treatment or
placebo-pill treatment (n = 50). In the Mind-Maastricht trial, individuals with
residual depressive symptoms were randomized to Mindfulness-Based Cognitive
Therapy (MBCT) or to a waiting-list control condition (n = 119). Lagged
associations among mental states, as assessed with the Experience Sampling Method
(ESM), were estimated at baseline and post-intervention. The results show that
few of the dynamic network connections changed significantly over time and few of
the changes after MBCT and imipramine treatment differed significantly from the
control groups. The decrease in average node connectivity after MBCT did not
differ from the decrease observed in the waiting-list control group. Our findings
suggest that imipramine treatment and MBCT do not greatly change the dynamic
network structure of mental states, even though they do reduce depressive
symptomatology.
PMID- 28425450
TI - Toxicological and biochemical basis of synergism between the entomopathogenic
fungus Lecanicillium muscarium and the insecticide matrine against Bemisia tabaci
(Gennadius).
AB - The sweetpotato whitefly Bemisia tabaci (Gennadius) was challenged with different
combinations of matrine (insecticide) and Lecanicillium muscarium
(entomopathogenic fungus). Our results revealed a synergistic relationship
between matrine and L. muscarium on mortality and enzyme activities of B. tabaci.
To illustrate the biochemical mechanisms involved in detoxification and immune
responses of B. tabaci against both control agents, activities of different
detoxifying and antioxidant enzymes were quantified. After combined application
of matrine and L. muscarium, activities of carboxylestrease (CarE), glutathione-s
transferase (GSTs) and chitinase (CHI) decreased during the initial infection
period. Acetylcholinestrase (AChE) activities increased during the entire
experimental period, whereas those of superoxide dismutase (SOD), peroxidase
(POD) and catalase (CAT) decreased during the later infection period. The
increased mortality and suppression of enzymatic response of B. tabaci following
matrine and L. muscarium application suggests a strong synergistic effect between
both agents. The strong synergistic effect is possibly related to the disturbance
of acetylcholine balance and changes in AchE activities of the whitefly as both
matrine and L. muscarium target insect acetylcholine (Ach) receptors which in
turn effects AchE production. Therefore, our results have revealed the complex
biochemical processes involved in the synergistic action of matrine and L.
muscarium against B. tabaci.
PMID- 28425451
TI - IFNbeta Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain
Injury.
AB - Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I
interferons (IFNalpha/beta) are critical mediators of any anti-viral immune
response and IFNbeta has been implicated in the temporary control of lentiviral
infection in the brain. Here we show that transgenic mice expressing HIV-1
envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a
transient IFNbeta response and provide evidence that IFNbeta confers neuronal
protection against HIVgp120 toxicity. In cerebrocortical cell cultures,
neuroprotection by IFNbeta against gp120 toxicity is dependent on IFNalpha
receptor 1 (IFNAR1) and the beta-chemokine CCL4, as IFNAR1 deficiency and
neutralizing antibodies against CCL4, respectively, abolish the neuroprotective
effects. We find in vivo that IFNbeta mRNA is significantly increased in
HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week
intranasal IFNbeta treatment of HIVgp120tg mice starting at 3.5 months of age
increases expression of CCL4 and concomitantly protects neuronal dendrites and
pre-synaptic terminals in cortex and hippocampus from gp120-induced damage.
Moreover, in vivo and in vitro data suggests astrocytes are a major source of
IFNbeta-induced CCL4. Altogether, our results suggest exogenous IFNbeta as a
neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced
brain injury.
PMID- 28425452
TI - Estimating the irreversible pressure drop across a stenosis by quantifying
turbulence production using 4D Flow MRI.
AB - The pressure drop across a stenotic vessel is an important parameter in medicine,
providing a commonly used and intuitive metric for evaluating the severity of the
stenosis. However, non-invasive estimation of the pressure drop under
pathological conditions has remained difficult. This study demonstrates a novel
method to quantify the irreversible pressure drop across a stenosis using 4D Flow
MRI by calculating the total turbulence production of the flow. Simulation MRI
acquisitions showed that the energy lost to turbulence production can be
accurately quantified with 4D Flow MRI within a range of practical spatial
resolutions (1-3 mm; regression slope = 0.91, R2 = 0.96). The quantification of
the turbulence production was not substantially influenced by the signal-to-noise
ratio (SNR), resulting in less than 2% mean bias at SNR > 10. Pressure drop
estimation based on turbulence production robustly predicted the irreversible
pressure drop, regardless of the stenosis severity and post-stenosis dilatation
(regression slope = 0.956, R2 = 0.96). In vitro validation of the technique in a
75% stenosis channel confirmed that pressure drop prediction based on the
turbulence production agreed with the measured pressure drop (regression slope =
1.15, R2 = 0.999, Bland-Altman agreement = 0.75 +/- 3.93 mmHg).
PMID- 28425453
TI - Aptamer-mediated impairment of EGFR-integrin alphavbeta3 complex inhibits
vasculogenic mimicry and growth of triple-negative breast cancers.
AB - Current treatment options for triple-negative breast cancers (TNBCs) is limited
by the absence of well-defined biomarkers, excluding a targeted therapy. Notably,
epidermal growth factor receptor (EGFR) is overexpressed in a great proportion of
TNBCs and is a negative prognostic factor. In clinical trials, however, existing
EGFR inhibitors showed disappointing outcome. Oligonucleotide aptamers are a
valid alternative to antibodies for diagnostic and therapeutic uses. Here, we
prove that, when applied to aggressive TNBC cell lines with unique stem-like
plasticity, the anti-EGFR CL4 aptamer, but not erlotinib or cetuximab, prevents
the vasculogenic mimicry (VM) capability of the cells and destroys previously
formed channels in three-dimensional culture. Notably, we found that CL4 impairs
the matrix-induced integrin alphavbeta3 interaction with EGFR and integrin
alphavbeta3-dependent cell adhesion. Consistently, the aptamer strongly inhibits
VM and tumor growth in a xenograft TNBC model. These data suggest that in TNBC
cells, EGFR may cooperate with integrin alphavbeta3 to regulate integrin binding
to extracellular ligands required for VM, and EGFR-targeting by CL4 aptamer may
counteract this event. Overall, we demonstrate a novel mechanism of action for
CL4 related with integrin alphavbeta3-EGFR interaction, that may help to develop
new oligonucleotide-based strategy addressing unmet need for TNBCs therapy.
PMID- 28425454
TI - Association of Serum Autotaxin Levels with Liver Fibrosis in Patients with
Chronic Hepatitis C.
AB - Metabolized by liver sinusoidal endothelial cells, autotaxin (ATX) is a secreted
enzyme considered to be associated with liver damage. We sought to clarify the
diagnostic ability of ATX for liver fibrosis in 593 biopsy-confirmed hepatitis C
virus (HCV)-infected patients. The diagnostic accuracy of ATX was compared with
clinical parameters and the established fibrosis biomarkers Wisteria floribunda
agglutinin-positive Mac-2-binding protein, FIB-4 index, AST-to-platelet ratio,
and Forn's index. Median ATX levels were consistently higher in female controls
and patients than in their male counterparts (P < 0.01). Serum ATX concentration
increased significantly according to liver fibrosis stage in overall and both
genders (P < 0.001). The cutoff values of ATX for prediction of fibrosis stages
>=F1, >=F2, >=F3, and F4 were 0.8, 1.1, 1.3, and 1.7 mg/L, respectively, in male
patients and 0.9, 1.7, 1.8, and 2.0 mg/L, respectively, in female patients. The
area under the receiver operating characteristic curve for ATX to diagnose
fibrosis of >=F2 (0.861) in male patients was superior to those of FIB-4 index
and Forn's index (P < 0.001), while that in female patients (0.801) was
comparable with those of the other markers. ATX therefore represents a novel non
invasive biomarker for liver fibrosis in HCV-infected patients.
PMID- 28425455
TI - The effect of hydraulic flowback and produced water on gill morphology, oxidative
stress and antioxidant response in rainbow trout (Oncorhynchus mykiss).
AB - Hydraulic fracturing fluid are complex mixtures containing high concentrations of
salts (up to 330,000 ppm), organic, and metal contaminants. However, little data
exist on the potential mechanisms of toxicity of these flowback and produced
wastewaters (FPW) on aquatic biota. Juvenile rainbow trout were exposed to either
control, FPW (2.5 or 7.5%), FPW that had been treated with activated charcoal
(AC), or a custom salt-matched control (SW; replicating only the salt content of
FPW) for 48 hours. Gill histology revealed decreases in interlamellar cell mass
(ILCM) and mean lamellar length in all treatments (FPW, AC and SW) compared to
control, indicative of hyperosmotic stress. Liver CYP1A1 activity was
significantly elevated by 7.5-fold in the FPW 7.5% treatment only, indicative of
Phase I metabolism. Superoxide dismutase activity significantly decreased in the
gills to all treatments with the lowest activity occurring in the 7.5% FPW group.
Catalase activity increased in liver with the highest values noted in fish
exposed to 7.5% FPW. No changes were observed with respect to glutathione-S
transferase, while increased lipid peroxidation was only observed in both FPW
treatments (2.5, 7.5%). These data suggest a characteristic signature of FPW
impact which may help in risk assessment and biomonitoring of FPW spills.
PMID- 28425456
TI - Salt suppresses IFNgamma inducible chemokines through the IFNgamma-JAK1-STAT1
signaling pathway in proximal tubular cells.
AB - The mechanisms of immunoactivation by salt are now becoming clearer. However,
those of immunosuppression remain unknown. Since clinical evidence indicates that
salt protects proximal tubules from injury, we investigated mechanisms
responsible for salt causing immunosuppression in proximal tubules. We focused on
cytokine-related gene expression profiles in kidneys of mice fed a high salt diet
using microarray analysis and found that both an interferon gamma (IFNgamma)
inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor,
CXCR3, were suppressed. We further revealed that a high salt concentration
suppressed IFNgamma inducible chemokines in HK2 proximal tubular cells. Finally,
we demonstrated that a high salt concentration decreased IFNGR1 expression in the
basolateral membrane of HK2 cells, leading to decreased phosphorylation of
activation sites of Janus kinase 1 (JAK1) and Signal Transducers and Activator of
Transcription 1 (STAT1), activators of chemokines. JAK inhibitor canceled the
effect of a high salt concentration on STAT1 and chemokines, indicating that the
JAK1-STAT1 signaling pathway is essential for this mechanism. In conclusion, a
high salt concentration suppresses IFNgamma-JAK1-STAT1 signaling pathways and
chemokine expressions in proximal tubules. This finding may explain how salt
ameliorates proximal tubular injury and offer a new insight into the linkage
between salt and immunity.
PMID- 28425457
TI - Strong Reduction of Thermal Conductivity and Enhanced Thermoelectric Properties
in CoSbS1-xSex Paracostibite.
AB - In order to reduce the thermal conductivity of CoSbS, a newly developed
thermoelectric semiconductor, we have aimed at intentionally induce atomic
disorder in its structure. This endeavor was guided by Density Functional
Theory(DFT) calculations which indicated that substituting sulfur with selenium
might be easily achievable experimentally because of the low formation energy of
this point defect. Thereby, CoSbS1-xSex compounds having 0 <= x <= 1 have been
synthesized by solid state reaction. Besides the expected semiconducting
paracostibite phase, we have observed the appearance of a semimetallic costibite
phase, never reported experimentally before. This cross-fertilized theoretical
and experimental approach allowed us to reduce by 50% the thermal conductivity of
paracostibite and therefore reach a maximum zT of 0.62 at 730 K. This makes this
entirely new CoSbS1-xSex alloy very attractive for further optimizations and
potential usage in thermoelectric applications.
PMID- 28425458
TI - Anatomy of terminal moraine segments and implied lake stability on Ngozumpa
Glacier, Nepal, from electrical resistivity tomography (ERT).
AB - Moraine-dammed lakes at debris-covered glaciers are becoming increasingly common
and pose significant outburst flood hazards if the dam is breached. While moraine
subsurface structure and internal processes are likely to influence dam
stability, only few sites have so far been investigated. We conducted electrical
resistivity tomography (ERT) surveys at two sites on the terminal moraine complex
of the Ngozumpa Glacier, Nepal, to aid assessment of future terminus stability.
The resistivity signature of glacier ice at the site (100-15 kOmega m) is more
consistent with values measured from cold glacier ice and while this may be
feasible, uncertainties in the data inversion introduce ambiguity to this thermal
interpretation. However, the ERT data does provide a significant improvement to
our knowledge of the subsurface characteristics at these sites, clearly showing
the presence (or absence) of glacier ice. Our interpretation is that of a highly
complex latero-terminal moraine, resulting from interaction between previous
glacier advance, recession and outburst flooding. If the base-level Spillway Lake
continues to expand to a fully formed moraine-dammed glacial lake, the
degradation of the ice core could have implications for glacial lake outburst
risk.
PMID- 28425459
TI - Complementary spin transistor using a quantum well channel.
AB - In order to utilize the spin field effect transistor in logic applications, the
development of two types of complementary transistors, which play roles of the n-
and p-type conventional charge transistors, is an essential prerequisite. In this
research, we demonstrate complementary spin transistors consisting of two types
of devices, namely parallel and antiparallel spin transistors using InAs based
quantum well channels and exchange-biased ferromagnetic electrodes. In these spin
transistors, the magnetization directions of the source and drain electrodes are
parallel or antiparallel, respectively, depending on the exchange bias field
direction. Using this scheme, we also realize a complementary logic operation
purely with spin transistors controlled by the gate voltage, without any
additional n- or p-channel transistor.
PMID- 28425460
TI - Modulation Doping of Silicon using Aluminium-induced Acceptor States in Silicon
Dioxide.
AB - All electronic, optoelectronic or photovoltaic applications of silicon depend on
controlling majority charge carriers via doping with impurity atoms. Nanoscale
silicon is omnipresent in fundamental research (quantum dots, nanowires) but also
approached in future technology nodes of the microelectronics industry. In
general, silicon nanovolumes, irrespective of their intended purpose, suffer from
effects that impede conventional doping due to fundamental physical principles
such as out-diffusion, statistics of small numbers, quantum- or dielectric
confinement. In analogy to the concept of modulation doping, originally invented
for III-V semiconductors, we demonstrate a heterostructure modulation doping
method for silicon. Our approach utilizes a specific acceptor state of aluminium
atoms in silicon dioxide to generate holes as majority carriers in adjacent
silicon. By relocating the dopants from silicon to silicon dioxide, Si nanoscale
doping problems are circumvented. In addition, the concept of aluminium-induced
acceptor states for passivating hole selective tunnelling contacts as required
for high-efficiency photovoltaics is presented and corroborated by first carrier
lifetime and tunnelling current measurements.
PMID- 28425461
TI - Real-time Crystal Growth Visualization and Quantification by Energy-Resolved
Neutron Imaging.
AB - Energy-resolved neutron imaging is investigated as a real-time diagnostic tool
for visualization and in-situ measurements of "blind" processes. This technique
is demonstrated for the Bridgman-type crystal growth enabling remote and direct
measurements of growth parameters crucial for process optimization. The location
and shape of the interface between liquid and solid phases are monitored in real
time, concurrently with the measurement of elemental distribution within the
growth volume and with the identification of structural features with a ~100 MUm
spatial resolution. Such diagnostics can substantially reduce the development
time between exploratory small scale growth of new materials and their subsequent
commercial production. This technique is widely applicable and is not limited to
crystal growth processes.
PMID- 28425462
TI - Role of chiral quantum Hall edge states in nuclear spin polarization.
AB - Resistively detected NMR (RDNMR) based on dynamic nuclear polarization (DNP) in a
quantum Hall ferromagnet (QHF) is a highly sensitive method for the discovery of
fascinating quantum Hall phases; however, the mechanism of this DNP and, in
particular, the role of quantum Hall edge states in it are unclear. Here we
demonstrate the important but previously unrecognized effect of chiral edge modes
on the nuclear spin polarization. A side-by-side comparison of the RDNMR signals
from Hall bar and Corbino disk configurations allows us to distinguish the
contributions of bulk and edge states to DNP in QHF. The unidirectional current
flow along chiral edge states makes the polarization robust to thermal
fluctuations at high temperatures and makes it possible to observe a reciprocity
principle of the RDNMR response. These findings help us better understand complex
NMR responses in QHF, which has important implications for the development of
RDNMR techniques.
PMID- 28425463
TI - Trends in the pervasiveness of type 2 diabetes, impaired fasting glucose and co
morbidities during an 8-year-follow-up of nationwide Korean population.
AB - The prevalence and incidence of type 2 diabetes, impaired fasting glucose, and co
morbidities from 2006 to 2013 in the population aged >=30 years were estimated
using the Korean NHIS database. The prevalence of type 2 diabetes increased 0.2
0.5% annually, from 5.6% in 2006 to 8% in 2013. The prevalence of type 2 diabetes
was higher in men than in women and increased with age. The incidence of type 2
diabetes was 0.81% in 2013 and was 1.4 times higher in men than in women and
increased with age. An overall decrease in the incidence rate occurred from 2006
to 2013(from 0.95 to 0.81%), which was mirrored in all age groups except the 30
39-year-old group. The prevalence of IFG was 25% in 2013. The prevalence of
hypertension(62.5 vs 16.9%) and dyslipidemia(49.5 vs 9.7%) were more prevalent in
patients with type 2 diabetes compared to non-diabetic cases. This study shows
that type 2 diabetes is both common and increasing and that one-quarter of the
Korean adult population has IFG. We also confirmed that the prevalence of
hypertension and dyslipidemia are 3.7-fold and 5.1-fold higher, respectively, in
diabetic patients than in non-diabetic adults.
PMID- 28425464
TI - Metabolic labelling of the carbohydrate core in bacterial peptidoglycan and its
applications.
AB - Bacterial cells are surrounded by a polymer known as peptidoglycan (PG), which
protects the cell from changes in osmotic pressure and small molecule insults. A
component of this material, N-acetyl-muramic acid (NAM), serves as a core
structural element for innate immune recognition of PG fragments. We report the
synthesis of modifiable NAM carbohydrate derivatives and the installation of
these building blocks into the backbone of Gram-positive and Gram-negative
bacterial PG utilizing metabolic cell wall recycling and biosynthetic
machineries. Whole cells are labelled via click chemistry and visualized using
super-resolution microscopy, revealing higher resolution PG structural details
and allowing the cell wall biosynthesis, as well as its destruction in immune
cells, to be tracked. This study will assist in the future identification of
mechanisms that the immune system uses to recognize bacteria, glean information
about fundamental cell wall architecture and aid in the design of novel
antibiotics.
PMID- 28425465
TI - Chytrid fungus infection in zebrafish demonstrates that the pathogen can
parasitize non-amphibian vertebrate hosts.
AB - Aquatic chytrid fungi threaten amphibian biodiversity worldwide owing to their
ability to rapidly expand their geographical distributions and to infect a wide
range of hosts. Combating this risk requires an understanding of chytrid host
range to identify potential reservoirs of infection and to safeguard uninfected
regions through enhanced biosecurity. Here we extend our knowledge on the host
range of the chytrid Batrachochytrium dendrobatidis by demonstrating infection of
a non-amphibian vertebrate host, the zebrafish. We observe dose-dependent
mortality and show that chytrid can infect and proliferate on zebrafish tissue.
We also show that infection phenotypes (fin erosion, cell apoptosis and muscle
degeneration) are direct symptoms of infection. Successful infection is dependent
on disrupting the zebrafish microbiome, highlighting that, as is widely found in
amphibians, commensal bacteria confer protection against this pathogen.
Collectively, our findings greatly expand the limited tool kit available to study
pathogenesis and host response to chytrid infection.
PMID- 28425466
TI - Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster
modulates DNA binding.
AB - NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes
through the progressive degradation of its [4Fe-4S] cluster on nitric oxide (NO)
exposure. We report the 1.95 A resolution crystal structure of dimeric holo
ScNsrR and show that the cluster is coordinated by the three invariant Cys
residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map
suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C
variants remain NO sensitive, DNA binding is affected. A structural comparison of
holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe-4S] cluster
stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact
with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97
from this turn, along with Arg12, which forms a salt-bridge with Asp8, are
instrumental in modulating the position of the DNA recognition helix region
relative to its major groove.
PMID- 28425467
TI - Hyperpolarized 13C Spectroscopic Evaluation of Oxidative Stress in a Rodent Model
of Steatohepatitis.
AB - Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now
considered the most common liver disease in the western world. Approximately one
third of patients with NASH develop non-alchoholic steatohepatitis (NASH),
histologically defined by lobular and portal inflammation, and accompanied by
marked oxidative stress. Patients with NASH are at increased risk for cirrhosis
and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy.
In animal models of NASH, particularly the methionine-choline deficient (MCD)
model, profound changes are seen in redox enzymes and key intracellular
antioxidants. To study antioxidant status in NASH non-invasively, we applied the
redox probe hyperpolarized [1-13C] dehydroascorbic acid (HP DHA), which is
reduced to Vitamin C (VitC) rapidly in the normal liver. In MCD mice, we observed
a significant decrease in HP DHA to VitC conversion that accompanied hepatic fat
deposition. When these animals were subsequently placed on a normal diet,
resonance ratios reverted to those seen in control mice. These findings suggest
that HP DHA, a potentially clinically translatable imaging agent, holds special
promise in imaging NASH and other metabolic syndromes, to monitor disease
progression and response to targeted therapies.
PMID- 28425468
TI - Transcriptome Analysis of Mango (Mangifera indica L.) Fruit Epidermal Peel to
Identify Putative Cuticle-Associated Genes.
AB - Mango fruit (Mangifera indica L.) are highly perishable and have a limited shelf
life, due to postharvest desiccation and senescence, which limits their global
distribution. Recent studies of tomato fruit suggest that these traits are
influenced by the expression of genes that are associated with cuticle
metabolism. However, studies of these phenomena in mango fruit are limited by the
lack of genome-scale data. In order to gain insight into the mango cuticle
biogenesis and identify putative cuticle-associated genes, we analyzed the
transcriptomes of peels from ripe and overripe mango fruit using RNA-Seq.
Approximately 400 million reads were generated and de novo assembled into 107,744
unigenes, with a mean length of 1,717 bp and with this information an online
Mango RNA-Seq Database (http://bioinfo.bti.cornell.edu/cgi-bin/mango/index.cgi)
which is a valuable genomic resource for molecular research into the biology of
mango fruit was created. RNA-Seq analysis suggested that the pathway leading to
biosynthesis of the cuticle component, cutin, is up-regulated during
overripening. This data was supported by analysis of the expression of several
putative cuticle-associated genes and by gravimetric and microscopic studies of
cuticle deposition, revealing a complex continuous pattern of cuticle deposition
during fruit development and involving substantial accumulation during
ripening/overripening.
PMID- 28425469
TI - In plastico: laboratory material newness affects growth and reproduction of
Daphnia magna reared in 50-ml polypropylene tubes.
AB - Plastic laboratory materials are found to affect vital parameters of the
waterflea Daphnia magna. The main responsible factor is defined as "newness" of
the materials. Juvenile D. magna were raised individually in; a) new laboratory
standard 50 ml polypropylene tubes, and; b) identical tubes which had been washed
and aerated for several weeks. Newness had significant effects on growth and
fecundity of D. magna. New tubes caused delayed maturation, reduced reproduction
and reduced growth when compared to washed and re-used tubes of the same
commercial brand. The findings indicate that newness of tubes has inhibiting or
toxic effects on D. magna. Often laboratory plastics are intended for single-use
due to sterility demands. Newness might be an important confounding factor in
research results and should not be disregarded. Disposable plastic utensils may
come with a seemingly ignored cost and induce adverse effects in biological test
organisms and systems. The presented findings accentuate continued need for
general awareness concerning confounding factors stemming from material
laboratory environment. Based on the present findings the authors suggest that
plastics intended for use in sensitive research may need to be washed and aerated
prior to use.
PMID- 28425470
TI - Graphene oxide as an interface phase between polyetheretherketone and
hydroxyapatite for tissue engineering scaffolds.
AB - The poor bonding strength between biopolymer and bioceramic has remained an
unsolved issue. In this study, graphene oxide (GO) was introduced as an interface
phase to improve the interfacial bonding between polyetheretherketone (PEEK) and
hydroxyapatite (HAP) for tissue engineering scaffolds. On the one hand, the
conjugated structure of GO could form strong pi-pi stacking interaction with the
benzene rings in PEEK. On the other hand, GO with a negatively charge resulting
from oxygen functional groups could adsorb the positively charged calcium atoms
(C sites) of HAP. Consequently, the dispersibility and compatibility of HAP in
the PEEK matrix increased with increasing GO content up to 1 wt%. At this time,
the compressive strength and modulus of scaffolds increased by 79.45% and 42.07%,
respectively. Furthermore, the PEEK-HAP with GO (PEEK-HAP/GO) scaffolds possessed
the ability to induce formation of bone-like apatite. And they could support
cellular adhesion, proliferation as well as osteogenic differentiation. More
importantly, in vivo bone defect repair experiments showed that new bone formed
throughout the scaffolds at 60 days after implantation. All these results
suggested that the PEEK-HAP/GO scaffolds have a promising potential for bone
tissue engineering application.
PMID- 28425471
TI - Nonspecific synaptic plasticity improves the recognition of sparse patterns
degraded by local noise.
AB - Many forms of synaptic plasticity require the local production of volatile or
rapidly diffusing substances such as nitric oxide. The nonspecific plasticity
these neuromodulators may induce at neighboring non-active synapses is thought to
be detrimental for the specificity of memory storage. We show here that memory
retrieval may benefit from this non-specific plasticity when the applied sparse
binary input patterns are degraded by local noise. Simulations of a biophysically
realistic model of a cerebellar Purkinje cell in a pattern recognition task show
that, in the absence of noise, leakage of plasticity to adjacent synapses
degrades the recognition of sparse static patterns. However, above a local noise
level of 20%, the model with nonspecific plasticity outperforms the standard,
specific model. The gain in performance is greatest when the spatial distribution
of noise in the input matches the range of diffusion-induced plasticity. Hence
non-specific plasticity may offer a benefit in noisy environments or when the
pressure to generalize is strong.
PMID- 28425472
TI - Label-free single-cell separation and imaging of cancer cells using an integrated
microfluidic system.
AB - The incidence of cancer is increasing worldwide and metastatic disease, through
the spread of circulating tumor cells (CTCs), is responsible for the majority of
the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical
information supporting therapeutic decision making, and improved methods for CTC
enumeration are asked for. Microfluidics has been extensively used for this
purpose but most methods require several post-separation processing steps
including concentration of the sample before analysis. This induces a high risk
of sample loss of the collected rare cells. Here, an integrated system is
presented that efficiently eliminates this risk by integrating label-free
separation with single cell arraying of the target cell population, enabling
direct on-chip tumor cell identification and enumeration. Prostate cancer cells
(DU145) spiked into a sample with whole blood concentration of the peripheral
blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at
a recovery of 76.2 +/- 5.9% of the cancer cells and a minute contamination of
0.12 +/- 0.04% PBMCs while simultaneously enabling a 20x volumetric
concentration. This constitutes a first step towards a fully integrated system
for rapid label-free separation and on-chip phenotypic characterization of
circulating tumor cells from peripheral venous blood in clinical practice.
PMID- 28425473
TI - 2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type
2 diabetes with different body mass index.
AB - Obesity and type 2 diabetes(T2D) are the most prevalent and serious metabolic
diseases affecting people worldwide. However racial and ethnic disparities seems
to be a risk factor for their development. Mexico has been named as one of the
largest populations with the highest prevalence of diabetes and obesity. The aim
of this study was to identify novel T2D-associated proteins in Mexican patients.
Blood samples were collected from 62 Mexican patients with T2D and they were
grouped according to their body mass index(BMI). A panel of 10 diabetes and
obesity serum markers was determined using MAGPIX. A comparative proteomics study
was performed using two-dimensional difference in-gel electrophoresis(2D-DIGE)
followed by mass spectrometry(LC-MS/MS). We detected 113 spots differentially
accumulated, in which 64 unique proteins were identified, proteins that were
involved in metabolism pathways, molecular transport, and cellular signalling.
Four proteins(14-3-3, ApoH, ZAG, and OTO3) showing diabetes-related variation and
also changes in relation to obesity were selected for further validation by
western blotting. Our results reveal new diabetes related proteins present in the
Mexican population. These could provide additional insight into the understanding
of diabetes development in Mexican population and may also be useful candidate
biomarkers.
PMID- 28425474
TI - Invasion of Ancestral Mammals into Dim-light Environments Inferred from Adaptive
Evolution of the Phototransduction Genes.
AB - Nocturnality is a key evolutionary innovation of mammals that enables mammals to
occupy relatively empty nocturnal niches. Invasion of ancestral mammals into
nocturnality has long been inferred from the phylogenetic relationships of crown
Mammalia, which is primarily nocturnal, and crown Reptilia, which is primarily
diurnal, although molecular evidence for this is lacking. Here we used
phylogenetic analyses of the vision genes involved in the phototransduction
pathway to predict the diel activity patterns of ancestral mammals and reptiles.
Our results demonstrated that the common ancestor of the extant Mammalia was
dominated by positive selection for dim-light vision, supporting the predominate
nocturnality of the ancestral mammals. Further analyses showed that the
nocturnality of the ancestral mammals was probably derived from the predominate
diurnality of the ancestral amniotes, which featured strong positive selection
for bright-light vision. Like the ancestral amniotes, the common ancestor of the
extant reptiles and various taxa in Squamata, one of the main competitors of the
temporal niches of the ancestral mammals, were found to be predominate diurnality
as well. Despite this relatively apparent temporal niche partitioning between
ancestral mammals and the relevant reptiles, our results suggested partial
overlap of their temporal niches during crepuscular periods.
PMID- 28425475
TI - Insecticidal activity of garlic essential oil and their constituents against the
mealworm beetle, Tenebrio molitor Linnaeus (Coleoptera: Tenebrionidae).
AB - This study evaluated the insecticidal activity of garlic, Allium sativum Linnaeus
(Amaryllidaceae) essential oil and their principal constituents on Tenebrio
molitor. Garlic essential oil, diallyl disulfide, and diallyl sulfide oil were
used to compare the lethal and repellent effects on larvae, pupae and adults of
T. molitor. Six concentrations of garlic essential oil and their principal
constituents were topically applied onto larvae, pupae and adults of this insect.
Repellent effect and respiration rate of each constituent was evaluated. The
chemical composition of garlic essential oil was also determined and primary
compounds were dimethyl trisulfide (19.86%), diallyl disulfide (18.62%), diallyl
sulfide (12.67%), diallyl tetrasulfide (11.34%), and 3-vinyl-[4H]-1,2-dithiin
(10.11%). Garlic essential oil was toxic to T. molitor larva, followed by pupa
and adult. In toxic compounds, diallyl disulfide was the most toxic than diallyl
sulfide for pupa > larva > adult respectively and showing lethal effects at
different time points. Garlic essential oil, diallyl disulfide and diallyl
sulfide induced symptoms of intoxication and necrosis in larva, pupa, and adult
of T. molitor between 20-40 h after exposure. Garlic essential oil and their
compounds caused lethal and sublethal effects on T. molitor and, therefore, have
the potential for pest control.
PMID- 28425476
TI - LncRNAs2Pathways: Identifying the pathways influenced by a set of lncRNAs of
interest based on a global network propagation method.
AB - Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in
diverse cellular processes and biological functions. Exploring the functions
associated with lncRNAs may help provide insight into their underlying biological
mechanisms. The current methods primarily focus on investigating the functions of
individual lncRNAs; however, essential biological functions may be affected by
the combinatorial effects of multiple lncRNAs. Here, we have developed a novel
computational method, LncRNAs2Pathways, to identify the functional pathways
influenced by the combinatorial effects of a set of lncRNAs of interest based on
a global network propagation algorithm. A new Kolmogorov-Smirnov-like statistical
measure weighted by the network propagation score, which considers the expression
correlation among lncRNAs and coding genes, was used to evaluate the biological
pathways influenced by the lncRNAs of interest. We have described the
LncRNAs2Pathways methodology and illustrated its effectiveness by analyzing three
lncRNA sets associated with glioma, prostate and pancreatic cancers. We further
analyzed the reproducibility and robustness and compared our results with those
of two other methods. Based on these analyses, we showed that LncRNAs2Pathways
can effectively identify the functional pathways associated with lncRNA sets.
Finally, we implemented this method as a freely available R-based tool.
PMID- 28425477
TI - MicroRNA-27a-3p Modulates the Wnt/beta-Catenin Signaling Pathway to Promote
Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by
Targeting SFRP1.
AB - This study aimed to elucidate how microRNA27a-3p (miR-27a-3p) modulates the
Wnt/beta-catenin signaling pathway to promote the epithelial-mesenchymal
transition (EMT) in oral squamous carcinoma stem cells (OSCSCs) by targeting
secreted frizzled-related protein 1 (SFRP1). Flow cytometry was used to sort
OSCSCs from the SCC-9 and Tca8113 cell lines. The OSCSCs were randomly assigned
into the miR-27a-3p inhibitors group, the miR-27a-3p inhibitors-NC group, the si
SFRP1 group, the si-SFRP1 + miR-27a-3p inhibitors group and the blank group. A
luciferase reporter, immunofluorescence and Transwell assays were performed to
detect luciferase activity, SFRP1, and cell migration and invasion, respectively.
The mRNA expression of miR-27a-3p, SFRP1 and EMT markers (E-cadherin, N-cadherin,
vimentin and ZEB1) were detected using qRT-PCR. The protein expression of SFRP1,
EMT markers and the proteins of the Wnt/beta-catenin signaling pathway was
detected by Western blotting. OSCSCs showed up-regulated miR-27a-3p, Wnt/beta
catenin signaling pathway-related proteins, vimentin, N-cadherin and ZEB1 and
down-regulated SFRP1 and E-cadherin. MiR-27a-3p targeted SFRP1. Down-regulated
miR-27a-3p resulted in increased E-cadherin and SFRP1 but decreased vimentin, N
cadherin, ZEB1, the Wnt/beta-catenin signaling pathway-related proteins, and
invasive and migratory cells. Silenced SFRP1 reversed this effect. We found that
miR-27a-3p modulated the Wnt/beta-catenin signaling pathway to promote EMT in
OSCSCs by down-regulating SFRP1.
PMID- 28425478
TI - Data Intensive Genome Level Analysis for Identifying Novel, Non-Toxic Drug
Targets for Multi Drug Resistant Mycobacterium tuberculosis.
AB - We report the construction of a novel Systems Biology based virtual drug
discovery model for the prediction of non-toxic metabolic targets in
Mycobacterium tuberculosis (Mtb). This is based on a data-intensive genome level
analysis and the principle of conservation of the evolutionarily important genes.
In the 1623 sequenced Mtb strains, 890 metabolic genes identified through a
systems approach in Mtb were evaluated for non-synonymous mutations. The 33 genes
showed none or one variation in the entire 1623 strains, including 1084 Russian
MDR strains. These invariant targets were further evaluated for their
experimental and in silico essentiality as well as availability of their crystal
structure in Protein Data Bank (PDB). Along with this, targets for the common
existing antibiotics and the new Tb drug candidates were also screened for their
variation across 1623 strains of Mtb for understanding the drug resistance. We
propose that the reduced set of these reported targets could be a more effective
starting point for medicinal chemists in generating new chemical leads. This
approach has the potential of fueling the dried up Tuberculosis (Tb) drug
discovery pipeline.
PMID- 28425479
TI - Perturbed oral motor control due to anesthesia during intraoral manipulation of
food.
AB - Sensory information from periodontal mechanoreceptors (PMRs) surrounding the
roots of natural teeth is important for optimizing the positioning of food and
adjustment of force vectors during precision biting. The present experiment was
designed to test the hypothesis; that reduction of afferent inputs from the PMRs,
by anesthesia, perturbs the oral fine motor control and related jaw movements
during intraoral manipulation of morsels of food. Thirty healthy volunteers with
a natural dentition were equally divided into experimental and control groups.
The participants in both groups were asked to manipulate and split a spherical
candy into two equal halves with the front teeth. An intervention was made by
anesthetizing the upper and lower incisors of the experimental group while the
control group performed the task without intervention. Performance of the split
was evaluated and the jaw movement recorded. The experimental group demonstrated
a significant decrease in measures of performance following local anesthesia.
However, there was no significant changes in the duration or position of the jaw
during movements in the experimental and control group. In conclusion, transient
deprivation of sensory information from PMRs perturbs oral fine motor control
during intraoral manipulation of food, however, no significant alterations in
duration or positions of the jaw during movements can be observed.
PMID- 28425480
TI - Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded
AAV9-GFP for gene therapy of neurological disorders.
AB - Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the
treatment of neurodegenerative diseases. While AAVs are generally administered
systemically to newborns in preclinical studies of neurological disorders, in
adults the maturity of the blood-brain barrier (BBB) must be considered when
selecting the route of administration. Delivery of AAVs into the cerebrospinal
fluid (CSF) represents an attractive approach to target the central nervous
system (CNS) and bypass the BBB. In this study, we investigated the efficacy of
intra-CSF delivery of a single-stranded (ss) AAV9-CAG-GFP vector in adult mice
via intracisternal (iCist) or intralumbar (it-Lumb) administration. It-Lumb
ssAAV9 delivery resulted in greater diffusion throughout the entire spinal cord
and green fluorescent protein (GFP) expression mainly in the cerebellum, cortex
and olfactory bulb. By contrast, iCist delivery led to strong GFP expression
throughout the entire brain. Comparison of the transduction efficiency of ssAAV9
CAG-GFP versus ssAAV9-SYN1-GFP following it-Lumb administration revealed
widespread and specific GFP expression in neurons and motoneurons of the spinal
cord and brain when the neuron-specific synapsin 1 (SYN1) promoter was used. Our
findings demonstrate that it-Lumb ssAAV9 delivery is a safe and highly efficient
means of targeting the CNS in adult mice.
PMID- 28425481
TI - Differences in salicylic acid glucose conjugations by UGT74F1 and UGT74F2 from
Arabidopsis thaliana.
AB - Salicylic acid (SA) is a signaling molecule utilized by plants in response to
various stresses. Through conjugation with small organic molecules such as
glucose, an inactive form of SA is generated which can be transported into and
stored in plant vacuoles. In the model organism Arabidopsis thaliana, SA glucose
conjugates are formed by two homologous enzymes (UGT74F1 and UGT74F2) that
transfer glucose from UDP-glucose to SA. Despite being 77% identical and with
conserved active site residues, these enzymes catalyze the formation of different
products: UGT74F1 forms salicylic acid glucoside (SAG), while UGT74F2 forms
primarily salicylic acid glucose ester (SGE). The position of the glucose on the
aglycone determines how SA is stored, further metabolized, and contributes to a
defense response. We determined the crystal structures of the UGT74F2 wild-type
and T15S mutant enzymes, in different substrate/product complexes. On the basis
of the crystal structures and the effect on enzyme activity of mutations in the
SA binding site, we propose the catalytic mechanism of SGE and SAG formation and
that SA binds to the active site in two conformations, with each enzyme selecting
a certain binding mode of SA. Additionally, we show that two threonines are key
determinants of product specificity.
PMID- 28425482
TI - Molecular differentiation of five Cinnamomum camphora chemotypes using desorption
atmospheric pressure chemical ionization mass spectrometry of raw leaves.
AB - Five chemotypes, the isoborneol-type, camphora-type, cineole-type, linalool-type
and borneol-type of Cinnamomum camphora (L.) Presl have been identified at the
molecular level based on the multivariate analysis of mass spectral fingerprints
recorded from a total of 750 raw leaf samples (i.e., 150 leaves equally collected
for each chemotype) using desorption atmospheric pressure chemical ionization
mass spectrometry (DAPCI-MS). Both volatile and semi-volatile metabolites of the
fresh leaves of C. camphora were simultaneously detected by DAPCI-MS without any
sample pretreatment, reducing the analysis time from half a day using
conventional methods (e.g., GC-MS) down to 30 s. The pattern recognition results
obtained using principal component analysis (PCA) was cross-checked by cluster
analysis (CA), showing that the difference visualized by the DAPCI-MS spectral
fingerprints was validated with 100% accuracy. The study demonstrates that DAPCI
MS meets the challenging requirements for accurate differentiation of all the
five chemotypes of C. camphora leaves, motivating more advanced application of
DAPCI-MS in plant science and forestry studies.
PMID- 28425484
TI - Mycobacterium tuberculosis resistance prediction and lineage classification from
genome sequencing: comparison of automated analysis tools.
AB - Whole-genome sequencing (WGS) has the potential to accelerate drug-susceptibility
testing (DST) to design appropriate regimens for drug-resistant tuberculosis
(TB). Several recently developed automated software tools promise to standardize
the analysis and interpretation of WGS data. We assessed five tools (CASTB,
KvarQ, Mykrobe Predictor TB, PhyResSE, and TBProfiler) with regards to DST and
phylogenetic lineage classification, which we compared with phenotypic DST,
Sanger sequencing, and traditional typing results for a collection of 91 strains.
The lineage classifications by the tools generally only differed in the
resolution of the results. However, some strains could not be classified at all
and one strain was misclassified. The sensitivities and specificities for
isoniazid and rifampicin resistance of the tools were high, whereas the results
for ethambutol, pyrazinamide, and streptomycin resistance were more variable.
False-susceptible DST results were mainly due to missing mutations in the
resistance catalogues that the respective tools employed for data interpretation.
Notably, we also found cases of false-resistance because of the misclassification
of polymorphisms as resistance mutations. In conclusion, the performance of
current WGS analysis tools for DST is highly variable. Sustainable business
models and a shared, high-quality catalogue of resistance mutations are needed to
ensure the clinical utility of these tools.
PMID- 28425485
TI - Red light improves spermatozoa motility and does not induce oxidative DNA damage.
AB - The ability to successfully fertilize ova relies upon the swimming ability of
spermatozoa. Both in humans and in animals, sperm motility has been used as a
metric for the viability of semen samples. Recently, several studies have
examined the efficacy of low dosage red light exposure for cellular repair and
increasing sperm motility. Of prime importance to the practical application of
this technique is the absence of DNA damage caused by radiation exposure. In this
study, we examine the effect of 633 nm coherent, red laser light on sperm
motility using a novel wavelet-based algorithm that allows for direct measurement
of curvilinear velocity under red light illumination. This new algorithm gives
results comparable to the standard computer-assisted sperm analysis (CASA)
system. We then assess the safety of red light treatment of sperm by analyzing,
(1) the levels of double-strand breaks in the DNA, and (2) oxidative damage in
the sperm DNA. The results demonstrate that for the parameters used there are
insignificant differences in oxidative DNA damage as a result of irradiation.
PMID- 28425483
TI - A genome-wide association study identifies six novel risk loci for primary
biliary cholangitis.
AB - Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong
hereditary component. Here, we report a genome-wide association study that
included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with
subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls.
Our results show genome-wide association of 14 PBC risk loci including previously
identified 6p21 (HLA-DRA and DPB1), 17q12 (ORMDL3), 3q13.33 (CD80), 2q32.3
(STAT1/STAT4), 3q25.33 (IL12A), 4q24 (NF-kappaB) and 22q13.1 (RPL3/SYNGR1). We
also identified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16
as novel PBC risk loci. These new findings and histochemical studies showing
enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic
portal tracks) support a disease mechanism in which the deregulation of the IL21
signalling pathway, in addition to CD4 T-cell activation and T-cell co
stimulation are critical components in the development of PBC.
PMID- 28425486
TI - Lamin B1 is required for mature neuron-specific gene expression during olfactory
sensory neuron differentiation.
AB - B-type lamins are major constituents of the nuclear lamina in all metazoan cells,
yet have specific roles in the development of certain cell types. Although they
are speculated to regulate gene expression in developmental contexts, a direct
link between B-type lamins and developmental gene expression in an in vivo system
is currently lacking. Here, we identify lamin B1 as a key regulator of gene
expression required for the formation of functional olfactory sensory neurons. By
using targeted knockout in olfactory epithelial stem cells in adult mice, we show
that lamin B1 deficient neurons exhibit attenuated response to odour stimulation.
This deficit can be explained by decreased expression of genes involved in mature
neuron function, along with increased expression of genes atypical of the
olfactory lineage. These results support that the broadly expressed lamin B1
regulates expression of a subset of genes involved in the differentiation of a
specific cell type.
PMID- 28425487
TI - Persimmon Leaves (Diospyros kaki) Extract Protects Optic Nerve Crush-Induced
Retinal Degeneration.
AB - Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we
report that the ethanol extract of Diospyros kaki (EEDK) exhibits protective
properties against retinal degeneration, both in vitro and in vivo. Upon exposure
to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability
versus the control, while pre-treatment with EEDK markedly increased cell
viability in a concentration-dependent manner. Further studies revealed that cell
survival induced by EEDK was associated with decreased levels of apoptotic
proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In
addition to apoptotic pathways, we demonstrated that expression levels of
antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S
transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In
a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on
retinal degeneration resulting from mechanical damages. Therefore, our results
suggest that EEDK may have therapeutic potential against retinal degenerative
disorders, such as glaucoma.
PMID- 28425488
TI - An Analytic Approach for Optimal Geometrical Design of GaAs Nanowires for Maximal
Light Harvesting in Photovoltaic Cells.
AB - Semiconductor nanowires(NWs) with subwavelength scale diameters have demonstrated
superior light trapping features, which unravel a new pathway for low cost and
high efficiency future generation solar cells. Unlike other published work, a
fully analytic design is for the first time proposed for optimal geometrical
parameters of vertically-aligned GaAs NW arrays for maximal energy harvesting.
Using photocurrent density as the light absorbing evaluation standard, 2 MUm
length NW arrays whose multiple diameters and periodicity are quantitatively
identified achieving the maximal value of 29.88 mA/cm2 under solar illumination.
It also turns out that our method has wide suitability for single, double and
four different diameters of NW arrays for highest photon energy harvesting. To
validate this analytical method, intensive numerical three-dimensional finite
difference time-domain simulations of the NWs' light harvesting are also carried
out. Compared with the simulation results, the predicted maximal photocurrent
densities lie within 1.5% tolerance for all cases. Along with the high accuracy,
through directly disclosing the exact geometrical dimensions of NW arrays, this
method provides an effective and efficient route for high performance
photovoltaic design.
PMID- 28425489
TI - MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome.
AB - Restless Legs Syndrome (RLS) is a genetically complex neurological disorder in
which overlapping genetic risk factors may contribute to the diversity and
heterogeneity of the symptoms. The main goal of the study was to investigate,
through analysis of heart rate variability (HRV), whether in RLS patients the
MEIS1 polymorphism at risk influences the sympathovagal regulation in different
sleep stages. Sixty-four RLS patients with periodic leg movement index above 15
per hour, and 38 controls underwent one night of video-polysomnographic
recording. HRV in the frequency- and time- domains was analyzed during nighttime
sleep. All RLS patients were genotyped, and homozygotes for rs2300478 in the
MEIS1 locus were used for further analysis. Comparison of the sympathovagal
pattern of RLS patients to control subjects did not show significant differences
after adjustments for confounding factors in frequency-domain analyses, but
showed an increased variability during N2 and N3 stages in time-domain analyses
in RLS patients. Sorting of RLS patients according to MEIS1 polymorphism
reconfirmed the association between MEIS1 and PLMS, and showed a significant
increased sympathovagal balance during N3 stage in those homozygotes for the risk
allele. RLS patients should be considered differently depending on MEIS1
genotype, some being potentially at risk for cardiovascular disorders.
PMID- 28425490
TI - Urinary and Fecal Metabonomics Study of the Protective Effect of Chaihu-Shu-Gan
San on Antibiotic-Induced Gut Microbiota Dysbiosis in Rats.
AB - Accumulating evidence suggests that the gut microbiota dysbiosis and their host
metabolic phenotype alteration is an important factor in human disease
development. A traditional Chinese herbal formula, Chaihu-Shu-Gan-San (CSGS), has
been effectively used in the treatment of various gastrointestinal (GI)
disorders. The present study was carried out to investigate whether CSGS
modulates the host metabolic phenotype under the condition of gut microbiota
dysbiosis. The metabonomics studies of biochemical changes in urine and feces of
antibiotic-induced gut microbiota dysbiosis rats after treatment with CSGS were
performed using UPLC-Q-TOF/MS. Partial least squares-discriminate analysis (PLS
DA) indicated that the CSGS treatment reduced the metabolic phenotype
perturbation induced by antibiotic. In addition, there was a strong correlation
between gut microbiota genera and urinary and fecal metabolites. Moreover, the
correlation analysis and the metabolic pathway analysis (MetPA) identified that
three key metabolic pathways including glycine, serine and threonine metabolism,
nicotinate and nicotinamide metabolism, and bile acid metabolism were the most
relevant pathways involved in antibiotic-induced gut microbiota dysbiosis. These
findings provided a comprehensive understanding of the protective effects of CSGS
on the host metabolic phenotype of the gut microbiota dysbiosis rats, and further
as a new source for drug leads in gut microbiota-targeted disease management.
PMID- 28425491
TI - The neural dynamics underlying the interpersonal effects of emotional expression
on decision making.
AB - Although numerous studies explore the effects of emotion on decision-making, the
existing research has mainly focused on the influence of intrapersonal emotions,
leaving the influence of one person's emotions on another's decisions
underestimated. To specify how interpersonal emotions shape decision-making and
delineate the underlying neural dynamics involved, the present study examined
brain responses to utilitarian feedback combined with angry or happy faces in
competitive and cooperative contexts. Behavioral results showed that participants
responded slower following losses than wins when competitors express happiness
but responded faster following losses than wins when cooperators express anger.
Importantly, angry faces in competitive context reversed the differentiation
pattern of feedback-related negativity (FRN) between losses and wins and
diminished the difference between losses and wins on both P300 and theta power,
but only diminished the difference on FRN between losses and wins in cooperative
context. However, when partner displays happiness, losses versus wins elicited
larger FRN and theta power in competitive context but smaller P300 in both
contexts. These results suggest that interpersonal emotions shape decisions
during both automatic motivational salience valuation (FRN) and conscious
cognitive appraisal (P300) stages of processing, in which different emotional
expressions exert interpersonal influence through different routes.
PMID- 28425492
TI - Fluorescence and Bioluminescence Imaging of Angiogenesis in Flk1-Nano-lantern
Transgenic Mice.
AB - Angiogenesis is important for normal development as well as for tumour growth.
However, the molecular and cellular mechanisms underlying angiogenesis are not
fully understood, partly because of the lack of a good animal model for imaging.
Here, we report the generation of a novel transgenic (Tg) mouse that expresses a
bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver
kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1
expression in endothelial cells and lymphatic endothelial cells during
development and tumour growth. Importantly, bioluminescence imaging of
endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled
us to observe endothelial sprouting for 18 hr without any detectable
phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse
luminescence imaging of tumour angiogenesis in freely moving mice with implanted
tumours. Thus, this transgenic mouse line contributes a unique model to study
angiogenesis within both physiological and pathological contexts.
PMID- 28425493
TI - Characterization of Different Microbubbles in Assisting Focused Ultrasound
Induced Blood-Brain Barrier Opening.
AB - Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in
CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open
the blood-brain barrier (BBB). However, limited understanding is available
regarding the effect of different microbubbles to induce BBB opening. The aim of
this study is to characterize different MBs on their effect in FUS-induced BBB
opening. Three MBs, SonoVue, Definity, and USphere, were tested, with 0.4-MHz FUS
exposure at 0.62-1.38 of mechanical index (MI) on rats. Evans blue, dynamic
contrast-enhanced (DCE) MRI and small-animal ultrasound imaging were used as
surrogates to allow molecule-penetrated quantification, BBB-opened observation,
and MBs circulation/persistence. Cavitation activity was measured via the passive
cavitation detection (PCD) setup to correlate with the exposure level and the
histological effect. Under given and identical MB concentrations, the three MBs
induced similar and equivalent BBB-opening effects and persistence. In addition,
a treatment paradigm by adapting exposure time is proposed to compensate MB decay
to retain the persistence of BBB-opening efficiency in multiple FUS exposures.
The results potentially improve understanding of the equivalence among MBs in
focused ultrasound CNS drug delivery, and provide an effective strategy for
securing persistence in this treatment modality.
PMID- 28425494
TI - Individual size but not additional nitrogen regulates tree carbon sequestration
in a subtropical forest.
AB - Recent studies have indicated that tree carbon accumulation in subtropical
forests has been negatively affected by global change phenomena such as warming
and drought. However, the long-term effect of nitrogen addition on plant carbon
storage remains poorly understood in these regions. In this study, we conducted a
10-year field experiment examining the effect of experimental N addition on plant
growth and carbon storage in a subtropical Chinese fir forest. The N levels were
0 (control), 60, 120, and 240 kg ha-1 yr-1, and the N effects on tree carbon were
divided into stand and individual levels. The results indicated that tree carbon
storage at the stand scale was not affected by long-term N addition in the
subtropical forest. By contrast, significant impacts of different tree size
classes on carbon sequestration were found under different N treatments, which
indicated that the amount of plant carbon sequestration was significantly
enhanced with tree size class. Our findings highlight the importance of community
structure and growth characteristics in Chinese fir forests, in which individual
size but not additional N regulates tree carbon sequestration in this subtropical
forest.
PMID- 28425495
TI - The BigLEN-GPR171 Peptide Receptor System Within the Basolateral Amygdala
Regulates Anxiety-Like Behavior and Contextual Fear Conditioning.
AB - Studies show that neuropeptide-receptor systems in the basolateral amygdala (BLA)
play an important role in the pathology of anxiety and other mood disorders.
Since GPR171, a recently deorphanized receptor for the abundant neuropeptide
BigLEN, is expressed in the BLA, we investigated its role in fear and anxiety
like behaviors. To carry out these studies we identified small molecule ligands
using a homology model of GPR171 to virtually screen a library of compounds. One
of the hits, MS0021570_1, was identified as a GPR171 antagonist based on its
ability to block (i) BigLEN-mediated activation of GPR171 in heterologous cells,
(ii) BigLEN-mediated hyperpolarization of BLA pyramidal neurons, and (iii)
feeding induced by DREADD-mediated activation of BigLEN containing AgRP neurons
in the arcuate nucleus. The role of GPR171 in anxiety-like behavior or fear
conditioning was evaluated following systemic or intra-BLA administration of
MS0021570_1, as well as following lentiviral-mediated knockdown of GPR171 in the
BLA. We find that systemic administration of MS0021570_1 attenuates anxiety-like
behavior while intra-BLA administration or knockdown of GPR171 in the BLA reduces
anxiety-like behavior and fear conditioning. These results indicate that the
BigLEN-GPR171 system plays an important role in these behaviors and could be a
novel target to develop therapeutics to treat psychiatric disorders.
PMID- 28425498
TI - A New Phenomenon: Sub-Tg, Solid-State, Plasticity-Induced Bonding in Polymers.
AB - Polymer self-adhesion due to the interdiffusion of macromolecules has been an
active area of research for several decades. Here, we report a new phenomenon of
sub-Tg, solid-state, plasticity-induced bonding; where amorphous polymeric films
were bonded together in a period of time on the order of a second in the solid
state at ambient temperatures, up to 60 K below their glass transition
temperature (Tg), by subjecting them to active plastic deformation. Despite the
glassy regime, the bulk plastic deformation triggered the requisite molecular
mobility of the polymer chains, causing interpenetration across the interfaces
held in contact. Quantitative levels of adhesion and the morphologies of the
fractured interfaces validated the sub-Tg, plasticity-induced, molecular
mobilization causing bonding. No-bonding outcomes (i) during the uniaxial
compressive straining of films (a near-hydrostatic setting which strongly limits
plastic flow) and (ii) between an 'elastic' and a 'plastic' film further
established the explicit role of plastic deformation in this newly reported sub
Tg solid-state bonding.
PMID- 28425496
TI - 3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel
Monkeys in a Serotonin 2A Receptor-Dependent Manner.
AB - 3,4-Methylenedioxymethamphetamine (MDMA) increases sociality in humans and
animals. Release of serotonin (5-HT) is thought to have an important role in the
increase in social behaviors, but the mechanisms underlying these effects are
poorly understood. Despite the advantages of nonhuman primate models, no studies
have examined the mechanisms of the social effects of MDMA in nonhuman primates.
The behavior and vocalizations of four group-housed squirrel monkeys were
examined following administration of MDMA, its enantiomers, and methamphetamine.
5-HT receptor antagonists and agonists were given as drug pretreatments. Data
were analyzed using linear mixed-effects models. MDMA and its enantiomers
increased affiliative social behaviors and vocalizations, whereas methamphetamine
had only modest effects on affiliative behaviors. Pretreatment with a 5-HT2A
receptor antagonist and a 5-HT2C receptor agonist attenuated the MDMA-induced
increase in social behaviors, while a 5-HT1A receptor antagonist did not alter
affiliative vocalizations and increased MDMA-induced social contact. Nonhuman
primates show MDMA-specific increases in affiliative social behaviors following
MDMA administration, in concordance with human and rodent studies. MDMA-induced
increases in social behaviors are 5-HT2A, but not 5-HT1A, receptor dependent.
Understanding the neurochemical mechanisms mediating the prosocial effects of
MDMA could help in the development of novel therapeutics with the unique social
effects of MDMA but fewer of its limitations.
PMID- 28425499
TI - Fake news threatens a climate literate world.
PMID- 28425497
TI - Single-Dose Memantine Improves Cortical Oscillatory Response Dynamics in Patients
with Schizophrenia.
AB - Aberrant gamma-band (30-80 Hz) oscillations may underlie cognitive deficits in
schizophrenia (SZ). Gamma oscillations and their regulation by NMDA receptors can
be studied via their evoked power (gammaEP) and phase locking (gammaPL) in
response to auditory steady-state stimulation; these auditory steady-state
responses (ASSRs) may be biomarkers for target engagement and early therapeutic
effects. We previously reported that memantine, an NMDA receptor antagonist,
enhanced two biomarkers of early auditory information processing: prepulse
inhibition and mismatch negativity (MMN) in SZ patients and healthy subjects
(HS). Here, we describe memantine effects on gammaEP and gammaPL in those
subjects. SZ patients (n=18) and HS (n=14) received memantine 20 mg (p.o.) and
placebo over 2 test days in a double-blind, randomized, counterbalanced, cross
over design. The ASSR paradigm (1 ms, 85 dB clicks in 250-0.5 s trains at a
frequency of 40 Hz; 0.5 s inter-train interval) was used to assess gammaEP and
gammaPL. SZ patients had reduced gammaEP and gammaPL; memantine enhanced gammaEP
and gammaPL (p<0.025 and 0.002, respectively) in both SZ and HS. In patients,
significant correlations between age and memantine effects were detected for
gammaEP and gammaPL: greater memantine sensitivity on gammaEP and gammaPL were
present in younger SZ patients, similar to our reported findings with MMN.
Memantine acutely normalized cortical oscillatory dynamics associated with NMDA
receptor dysfunction in SZ patients. Ongoing studies will clarify whether these
acute changes predict beneficial clinical, neurocognitive and functional
outcomes. These data support the use of gamma-band ASSR as a translational end
point in pro-cognitive drug discovery and early-phase clinical trials.
PMID- 28425500
TI - Structure Shapes Dynamics and Directionality in Diverse Brain Networks:
Mathematical Principles and Empirical Confirmation in Three Species.
AB - Identifying how spatially distributed information becomes integrated in the brain
is essential to understanding higher cognitive functions. Previous computational
and empirical studies suggest a significant influence of brain network structure
on brain network function. However, there have been few analytical approaches to
explain the role of network structure in shaping regional activities and
directionality patterns. In this study, analytical methods are applied to a
coupled oscillator model implemented in inhomogeneous networks. We first derive a
mathematical principle that explains the emergence of directionality from the
underlying brain network structure. We then apply the analytical methods to the
anatomical brain networks of human, macaque, and mouse, successfully predicting
simulation and empirical electroencephalographic data. The results demonstrate
that the global directionality patterns in resting state brain networks can be
predicted solely by their unique network structures. This study forms a
foundation for a more comprehensive understanding of how neural information is
directed and integrated in complex brain networks.
PMID- 28425502
TI - Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue
Scan Simulations.
AB - VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock
system. Upon blue light activation, a covalent bond is formed between VVD residue
Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD
switching from Dark state to Light state with significant conformational
deviation. However, the mechanism of this local environment initiated global
protein conformational change remains elusive. We employed a recently developed
computational approach, rigid residue scan(RRS), to systematically probe the
impact of the internal degrees of freedom in each amino acid residue of VVD on
its overall dynamics by applying rigid body constraint on each residue in
molecular dynamics simulations. Key residues were identified with distinctive
impacts on Dark and Light states, respectively. All the simulations display wide
range of distribution on a two-dimensional(2D) plot upon structural root-mean
square deviations(RMSD) from either Dark or Light state. Clustering analysis of
the 2D RMSD distribution leads to 15 representative structures with drastically
different conformation of N-terminus, which is also a key difference between Dark
and Light states of VVD. Further principle component analyses(PCA) of RRS
simulations agree with the observation of distinctive impact from individual
residues on Dark and Light states.
PMID- 28425501
TI - Plant gum identification in historic artworks.
AB - We describe an integrated and straightforward new analytical protocol that
identifies plant gums from various sample sources including cultural heritage.
Our approach is based on the identification of saccharidic fingerprints using
mass spectrometry following controlled enzymatic hydrolysis. We developed an
enzyme cocktail suitable for plant gums of unknown composition. Distinctive MS
profiles of gums such as arabic, cherry and locust-bean gums were successfully
identified. A wide range of oligosaccharidic combinations of pentose, hexose,
deoxyhexose and hexuronic acid were accurately identified in gum arabic whereas
cherry and locust bean gums showed respectively PentxHexy and Hexn profiles.
Optimized for low sample quantities, the analytical protocol was successfully
applied to contemporary and historic samples including 'Colour Box Charles
Roberson &Co' dating 1870s and drawings from the American painter Arthur Dove
(1880-1946). This is the first time that a gum is accurately identified in a
cultural heritage sample using structural information. Furthermore, this
methodology is applicable to other domains (food, cosmetic, pharmaceutical,
biomedical).
PMID- 28425503
TI - Nerve degeneration and regeneration in the cephalopod mollusc Octopus vulgaris:
the case of the pallial nerve.
AB - Regeneration is a process that restores structure and function of tissues damaged
by injury or disease. In mammals complete regeneration is often unsuccessful,
while most of the low phyla animals can re-grow many parts of their body after
amputation. Cephalopod molluscs, and in particular Octopus vulgaris, are well
known for their capacity to regenerate their arms and other body parts, including
central and peripheral nervous system. To better understand the mechanism of
recovery following nerve injury in this species we investigated the process of
axon regrowth and nerve regeneration after complete transection of the Octopus
pallial nerves. This injury induces scar formation and activates the
proliferation of hemocytes which invade the lesion site. Hemocytes appear
involved in debris removal and seem to produce factors that foster axon re
growth. Connective tissue is involved in driving regenerating fibers in a single
direction, outlining for them a well-defined pathway. Injured axons are able to
quickly re-grow thus to restoring structure and function.
PMID- 28425504
TI - SUV39H1 Reduction Is Implicated in Abnormal Inflammation in COPD.
AB - Chronic obstructive pulmonary disease(COPD) is characterized by enhanced chronic
inflammation in the airways, lung parenchyma, and circulation. We investigated
whether SUV39H1, a histone methyltransferase, is causatively implicated in the
abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were
reduced in peripheral blood mononuclear cells(PBMCs), primary human small airway
epithelial cells(HSAEpCs) and lung tissues from COPD patients, which were
correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific
SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory
cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and
H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked
unstimulated COPD HSAEpCs and led to decreased HP-1alpha levels and increased RNA
polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD
inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3
levels and suppressed inflammation. In COPD mice, chaetocin further repressed the
SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls
a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a
loss of the repressive chromatin mark H3K9me3 and confers an abnormal
inflammatory response to stimulators. SUV39H1 and its regulatory pathways are
potential therapeutic targets for COPD.
PMID- 28425505
TI - Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the
CDKN1 family of cell cycle inhibitors.
AB - Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes
patients to develop different highly vascularized cancers. pVHL targets the
hypoxia-inducible transcription factor (HIF-1alpha) for degradation, modulating
the activation of various genes involved in hypoxia response. Hypoxia plays a
relevant role in regulating cell cycle progression, inducing growth arrest in
cells exposed to prolonged oxygen deprivation. However, the exact molecular
details driving this transition are far from understood. Here, we present novel
interactions between pVHL and the cyclin-dependent kinase inhibitor family CDKN1
(p21, p27 and p57). Bioinformatics analysis, yeast two-hybrid screening and co
immunoprecipitation assays were used to predict, dissect and validate the
interactions. We found that the CDKN1 proteins share a conserved region mimicking
the HIF-1alpha motif responsible for pVHL binding. Intriguingly, a p27 site
specific mutation associated to cancer is shown to modulate this novel
interaction. Our findings suggest a new connection between the pathways
regulating hypoxia and cell cycle progression.
PMID- 28425507
TI - Recent advances in boronic acid-based optical chemosensors.
AB - Reversible covalent binding of boronic acids with polyols and Lewis bases has
facilitated the development of robust chemosensors for many biologically
important species under physiologically or environmentally relevant conditions.
This minireview covers selected examples of advances reported in this area from
2014 to 2016. While the discovery of new boron-containing binding motifs and
identification of new analytical targets have expanded the ultility of boronic
acid-based molecular recognition, unconventional sensing strategies such as
exploitation of nanoscale self-assembly, multicomponent dynamic covalent
assembly, and coupling boronate ester formation with a further chemical reaction
have led to significantly improved sensor performance, enabling real-world
applications in various areas such as cell biology and asymmetric catalysis.
PMID- 28425508
TI - Spin-state modulation of molecular FeIII complexes via inclusion in halogen
bonded supramolecular networks.
AB - The cationic complex [Fe(qsal)2]+ (Hqsal = N-(8-quinolyl)salicylaldimine) is
encapsulated in anionic halogen-bonded 1D and 2D networks derived from sym
triiodotrifluorobenzene, [(C6F3I3)Cl]- and [(C6F3I3)I]-. Structural analysis and
magnetic measurements show that the spin-state of this complex can be modulated
by its inclusion in supramolecular host frameworks.
PMID- 28425506
TI - Oncogenic activity of SOX1 in glioblastoma.
AB - Glioblastoma remains the most common and deadliest type of brain tumor and
contains a population of self-renewing, highly tumorigenic glioma stem cells
(GSCs), which contributes to tumor initiation and treatment resistance.
Developmental programs participating in tissue development and homeostasis re
emerge in GSCs, supporting the development and progression of glioblastoma. SOX1
plays an important role in neural development and neural progenitor pool
maintenance. Its impact on glioblastoma remains largely unknown. In this study,
we have found that high levels of SOX1 observed in a subset of patients correlate
with lower overall survival. At the cellular level, SOX1 expression is elevated
in patient-derived GSCs and it is also higher in oncosphere culture compared to
differentiation conditions in conventional glioblastoma cell lines. Moreover,
genetic inhibition of SOX1 in patient-derived GSCs and conventional cell lines
decreases self-renewal and proliferative capacity in vitro and tumor initiation
and growth in vivo. Contrarily, SOX1 over-expression moderately promotes self
renewal and proliferation in GSCs. These functions seem to be independent of its
activity as Wnt/beta-catenin signaling regulator. In summary, these results
identify a functional role for SOX1 in regulating glioma cell heterogeneity and
plasticity, and suggest SOX1 as a potential target in the GSC population in
glioblastoma.
PMID- 28425509
TI - A macrocyclic 'Co0' complex: the relevance of ligand non-innocence to reactivity.
AB - We present a formally zero-valent compound, [Co(Mabiq)Na(OEt2)]2 (1). The complex
was characterized by crystallographic, spectroscopic and DFT computational
methods. The electronic structure is described as a CoII-(ligand-biradical).
Compound 1 is reactive toward proton sources; CoI or CoII products result,
depending on the source of protons used. The redox non-innocence of the Mabiq
ligand, which accepts both protons and electrons, has important ramifications for
reactivity.
PMID- 28425510
TI - A universal split spinach aptamer (USSA) for nucleic acid analysis and DNA
computation.
AB - We demonstrate how a single universal spinach aptamer (USSA) probe can be used to
detect multiple (potentially any) nucleic acid sequences. USSA can be used for
cost-efficient and highly selective analysis of even folded DNA and RNA analytes,
as well as for the readout of outputs of DNA logic circuits.
PMID- 28425511
TI - Conjunctive functionalization of vinyl boronate complexes with electrophiles: a
diastereoselective three-component coupling.
AB - A method for the conjunctive functionalization of vinyl boronate complexes with
electrophiles is described. The overall process represents a three-component
coupling between a vinyl boronic ester, carbon nucleophile and an electrophile,
thus affording complex multifunctionalized products from simple starting
materials. The diastereoselectivity (syn or anti) of this process is strongly
dependent upon the nature of the electrophile.
PMID- 28425512
TI - "Colored" inorganic dopants for inducing liquid crystal chiral nematic and blue
phases: monitoring of dopant-host interaction by Raman spectroscopy.
AB - A new ruthenium complex that effectively induces chiral nematic and blue phases
upon doping with a nematic liquid crystal was developed. The red-colored dopant
exhibits strong Raman scattering in solution and nematics even at low
concentrations. Further measurements at various concentrations strongly suggested
homogeneous dispersion of the dopant in chiral nematics.
PMID- 28425513
TI - Regioselective copper-catalyzed direct arylation of benzodithiophene-S,S
tetraoxide.
AB - An efficient copper-catalyzed direct arylation reaction for the regioselective
functionalization of benzodithiophene-S,S-tetraoxide has been developed. The
method demonstrates a broad scope with isolated yields ranging from good to
excellent. Furthermore, the reaction specificity for aryl iodides over the
unreactive aryl bromides provide a opportunity to generate a new donor-acceptor
donor triad.
PMID- 28425514
TI - A Fe5C2 nanocatalyst for the preferential synthesis of ethanol via dimethyl
oxalate hydrogenation.
AB - A Fe-based catalyst exhibits extremely high selectivity (89.6%) besides excellent
catalytic activity in gas-phase dimethyl oxalate hydrogenation. The ethanol
formation occurs via hydrogenation of methyl acetate instead of ethylene glycol
over the active species Fe5C2.
PMID- 28425515
TI - The role of thermodynamic stability in the characteristics of the devitrification
front of vapour-deposited glasses of toluene.
AB - Physical vapour deposition (PVD) has settled in as an alternative method to
prepare glasses with significantly enhanced properties, providing new insights
into the understanding of glass transition. One of the striking properties of
some PVD glasses is their transformation into liquid via a heterogeneous
mechanism that initiates at surfaces/interfaces. Here, we use membrane-based fast
scanning nanocalorimetry (104 K s-1) to analyse the variables that govern the
transformation mechanism of vapour-deposited toluene glasses with different
stabilities. Thin films ranging from 20 to 250 nm were prepared at deposition
temperatures between 0.70 and 1.15 times the glass transition temperature. We
show how a propagating growth front is the initial transformation mechanism in
all the vapour deposited samples, revealing a clear tendency to faster front
velocities for less stable samples. Contrary to other glass-formers such as
indomethacin, toluene shows a one-to-one relationship between limiting fictive
temperature and front velocity. We associate this behaviour with the much simpler
molecular geometry of toluene, which would prevent the presence of strong
preferential molecular arrangements in the glass. However, the propagation
distance of the growth front before the homogenous transformation mechanism
dominates the transition is found to be dependent on the preparation conditions
rather than on the thermal stability of the glass. Understanding the link between
the growth variables and the properties of PVD glasses is crucial for finding and
developing potential applications of this type of glass.
PMID- 28425516
TI - Mechanical and vibrational characterization of amyloid-like HET-s nanosheets
based on the skewed plate theory.
AB - Pathological amyloidogenic prion proteins have a toxic effect on functional cells
in the human cerebrum because of poor degradability and the tendency to
accumulate in an uncontrolled manner under physiological conditions. HET-s, a
fungal prion protein, is known to undergo conformational variations from
fibrillar to nanosheet structures during a change from low to high pH conditions.
It has been said that this conformational change can lead to self-propagation by
nucleating on the lateral surface of singlet fibrils. Efforts have been made
toward the mechanical characterization of fibrillar amyloids, but a global
understanding of amyloid-like HET-s nanosheet structures is lacking. In this
study, we analyzed the mechanical and vibrational characteristics of the skewed
HET-s nanosheet structures that developed under neutral pH conditions by
performing various molecular dynamics simulations. By applying the skewed plate
theory to HET-s nanosheets for various length scales with numerous pores inside
the structures, we found that the skewed HET-s nanosheet structure has mechanical
properties comparable to those of previously reported biological film materials
and nanomaterials. Considering the inherent characteristics of structural
stability, our observation provides valuable and detailed structural information
on skewed amyloid-like HET-s nanosheets.
PMID- 28425517
TI - Diels-Alder reactions of graphene oxides: greatly enhanced chemical reactivity by
oxygen-containing groups.
AB - Graphene oxides (GOs) or reduced GOs (rGOs) may offer extraordinary potential for
chemical functionalization of graphene due to their unique electronic and
structural properties. By means of dispersion-corrected density functional theory
computations, we systematically investigated the Diels-Alder (DA) chemistry of
GOs. Our computations showed that the dual nature of GOs as both a diene and a
dienophile is stronger than that of pristine graphene. Interestingly, the
interior bonds of a graphene surface modified by oxygen-containing groups could
be functionalized by maleic anhydride (MA) and 2,3-dimethoxybutadiene (DMBD)
through cycloaddition reactions, and the cycloaddition products of MA and DMBD
are more favorable than the non-covalent complexes between these reagents and the
GO surface. The feasibility of covalent functionalization of GOs as a diene and a
dienophile strongly depends on the local structural environment of the oxygen
groups, including the atomic arrangement and the number of these groups
surrounding the reaction site. The exothermicities for (4+2) adducts of DMBD with
GO are far larger than those of MA, which indicates that the dienophile character
of the GO surface is stronger than its behavior as a diene.
PMID- 28425518
TI - Dynamic manipulation of the local pH within a nanopore triggered by surface
induced phase transition.
AB - Manipulating the local pH within nanoconfinement is essential in nanofluidics
technology and its applications. Since the conventional strategy utilizes the
overlapping of an electric double layer formed for charge compensation by protons
near a negatively charged pore-wall surface, pH variation within a pore is
limited to the acidic side. To achieve the variation at the alkaline side, we
developed a system comprising a hydrophobic pore-wall surface and aqueous
solution containing hydrophobic cations. Beyond a threshold cation concentration,
a nanopore is filled with the second phase where the cations are remarkably
enriched due to surface-induced phase transition (SIFT) originating from the
hydrophobic effect. It is accompanied by the enrichment of coexisting anions. We
experimentally show that pH in the second phase is much higher than in the bulk
solution. Electrochemical measurements strongly suggest that the pH value can be
increased from 4.8 to 10.7 within a 10 nm nanopore in the most significant case.
This is ascribed to the enrichment of hydroxide anions. We argue that the extent
and rate of pH variation are controlled as desired.
PMID- 28425519
TI - Electrolytic conductivity-related radiofrequency heating of aqueous suspensions
of nanoparticles for biomedicine.
AB - The development of suitable contrast agents can significantly enhance the
efficiency of modern imaging and treatment techniques, such as thermoacoustic
(TA) tomography and radio-frequency (RF) hyperthermia of cancer. Here, we examine
the heating of aqueous suspensions of silicon (Si) and gold (Au) nanoparticles
(NPs) under RF irradiation in the MHz frequency range. The heating rate of
aqueous suspensions of Si NPs exhibited non-monotonic dependency on the
electrical conductivity of the suspension. The experimental results were
explained by the mathematical model considering oscillating solvated ions as the
main source of Joule heating. These ions could be the product of the dissolution
of Si NPs or organic coating of Au NPs. Thus, the ions governed the conductivity
of the suspensions, which in turn governs both the heating rate and the near
field RF TA response. The model predicted the contrast in different tissues
taking into account both Joule heating and dielectric losses.
PMID- 28425520
TI - An innovative chemical strategy for PCR-free genetic detection of pathogens by an
integrated electrochemical biosensor.
AB - An innovative chemical strategy integrated in a miniaturized electrochemical
device was developed for sensitive detection of a pathogen genome (HBV virus)
without any amplification step. The results show a limit of detection comparable
to the standard qRT-PCR method (20 copies per reaction), paving the way to future
development of genetic PoC devices addressing automatized and low-cost molecular
diagnostics.
PMID- 28425522
TI - Red luminescence control of Eu(iii) complexes by utilizing the multi-colored
electrochromism of viologen derivatives.
AB - The electroresponsive switching of red photoluminescence based on the
electrochemical coloration of cyan-magenta-green (CMG) viologen components was
achieved by combining a luminescent Eu3+ chelate and viologen derivatives,
resulting in CMG coloration in a single cell. The cell coloration was controlled
by an electrochromic (EC) reaction, which also modulated the photoluminescence of
the Eu3+ chelate with high contrast, by transferring energy from the excited
state of the Eu3+ ion to the colored states of EC molecules. Cyclic
voltammograms, photoluminescence spectra, absorption spectra, luminescence
quantum yields, and luminescence lifetimes were measured to clarify the
differences between the luminescence quenching and energy transfer efficiencies
for each C, M, and G coloration associated with the electrochromism. Thus, the
spectral overlap between the luminescence band of the Eu3+ chelate and the
absorption band of the colored EC molecules was proven to affect the efficiency
of luminescence modulation.
PMID- 28425521
TI - Chemical genomic analysis of GPR35 signaling.
AB - GPR35, a family A orphan G protein-coupled receptor, has been implicated in
inflammatory, neurological, and cardiovascular diseases. However, not much is
known about the signaling and functions of GPR35. We performed a label-free
kinome short hairpin RNA screen and identified a putative signaling network of
GPR35 in HT-29 cells, some of which was validated using gene expression,
biochemical and cellular assays. The results showed that GPR35 induced hypoxia
inducible factor 1alpha, and was involved in synaptic transmission, sensory
perception, the immune system, and morphogenetic processes. Collectively, our
data suggest that GPR35 may play an important role in response to hypoxic stress
and be a potential target for the treatment of inflammatory, cardiovascular, and
neurological disorders.
PMID- 28425523
TI - A synthetic co-crystal prepared by cooperative single-crystal-to-single-crystal
solid-state Diels-Alder reaction.
AB - A single-crystal-to-single-crystal solid-state reaction involving the 2 : 1
charge-transfer complex of 9-bromoanthracene and bis(N-cyclobutylimino)-1,4
dithiin leads to a synthetic co-crystal composed of the Diels-Alder cycloadduct
and unreacted 9-bromoanthracene molecules. Analysis of close contacts in the
product crystal and DFT energy calculations indicate an ordered arrangement of
product and unreacted molecules due to cooperative effects during the reaction.
PMID- 28425524
TI - Excited state relaxation processes of H2-evolving Ru-Pd supramolecular
photocatalysts containing a linear or non-linear bridge: a DFT and TDDFT study.
AB - In this study, the early-time excited state relaxation processes of bimetallic Ru
Pd supramolecular photocatalysts containing a linear 2,2':5',2''-terpyridine or a
nonlinear 2,2':6',2''-terpyridine bridging ligand (BL) were investigated by
density functional theory (DFT) and time-dependent DFT (TDDFT) approaches. The
bridge based metal-to-ligand charge transfer triplet (3MLCT) state of the metal
complex containing a linear bridging ligand was calculated to be the lowest
energy triplet (T1) state which is closely related to the photocatalytic H2
production, while for that having a nonlinear bridging ligand, the T1 state is a
Ru metal-centered (MC) triplet (3MCRu) state that is short-lived and rapidly
decays to the ground electronic state (S0). Our simulation provides an
alternative explanation for the smaller interligand electron transfer (ILET) rate
in the Ru-Pd complex containing a linear bridge compared to the corresponding
monometal Ru complex. Based on the calculation, we also suggest that the
successive 3MLCT -> 3MCRu -> S0 conversion is responsible for the inefficiency of
the Ru-Pd complex containing nonlinear bridge as a photocatalyst for H2
production. This study provides theoretical insights into the key steps of the
photoinduced processes of the bimetallic H2-evolving supramolecular
photocatalyst.
PMID- 28425525
TI - Exploiting hydrogen bonding interactions to probe smaller linear and cyclic
diamines binding to G-quadruplexes: a DFT and molecular dynamics study.
AB - G-quadruplexes are formed by the association of four guanine bases through
Hoogsteen hydrogen bonding in guanine-rich sequences of DNA and exist in the
telomere as well as in promoter regions of certain oncogenes. The sequences of G
quadruplex-DNA are targets for the design of molecules that can bind and can be
developed as anti-cancer drugs. The linear and cyclic protonated diamines have
been explored to bind to G-quadruplex-DNA through hydrogen bonding interactions.
The quadruplex-DNA binders exploit pi-stacking and hydrogen bonding interactions
with the phosphate backbone of loops and grooves. In this study, linear and
cyclic protonated diamines showed remarkable binding affinity for G-tetrads using
hydrogen bonding interactions. The DFT M06-2X/6-31G(d)//B3LYP/6-31+G(d) level of
theory showed that the cyclic ee-1,2-CHDA (equatorial-equatorial form of 1,2
disubstituted cyclohexadiamine di-cation) binds to the G-tetrads very strongly
(~70.0 kcal mol-1), with a much higher binding energy than the linear protonated
diamines. The binding affinity of ligands for G-tetrads with counterions has also
been examined. The binding preference of these small ligands for G-tetrads is
higher than for DNA-duplex. The binding affinity of an intercalated acridine
based ligand (BRACO-19) for G-quadruplexes has been examined and the binding
energy is relatively lower than that for the 1,2 disubstituted cyclohexadiamine
di-cation with G-tetrads. The atoms-in-molecules (AIM) analysis reveals that the
hydrogen bonding interactions between the organic systems with G-tetrads are
primarily electrostatic in nature. The molecular dynamics simulations performed
using a classical force field (GROMACS) also supported the phosphate backbone
sites of G-quadruplex-DNA to bind to these diamines. To mimic the structural
pattern of BRACO-19, the designed inhibitor N,2-bis-2(3,4-aminocyclohexyl)
acetamide (9) examined possesses two 1,2-CHDA moieties linked through an
acetamide group. The molecular dynamics results showed that the designed molecule
9 can efficiently bind to the base-pairs and the phosphate backbone of G
quadruplex-DNA using H-bonding interactions. The binding affinity calculated for
the intercalated acridine-based drug (BRACO-19) with G-quadruplexes is weaker
compared to ee-1,2-CHDA. These ligands deliver a different binding motif
(hydrogen bonding) compared to the reported G-quadruplex binders of pi
delocalized systems and will kindle interest in examining such scaffolds to
stabilize DNA.
PMID- 28425527
TI - Synthesis of SAPO-34 nanoaggregates with the assistance of an inexpensive three
in-one non-surfactant organosilane.
AB - [3-Piperazinepropylmethyldimethoxysilane (PZPMS)] as a low-cost co-template, a
crystal growth inhibitor, and a part of the silica source was used together with
triethylamine to synthesize SAPO-34 nanoaggregates with tunable compositions.
Note that the piperazinyl group of PZPMS prompts the formation of a perfect CHA
structure by eliminating the CHA/AEI intergrowth, which ensures the excellent MTO
catalytic performance of SAPO-34 nanoaggregates.
PMID- 28425528
TI - Chemomechanical oscillations with a non-redox non-oscillatory reaction.
AB - Periodic length changes, over 20%, were sustained in a pH-responsive gel by
associating the methylene glycol-sulphite OH-producing clock-reaction with
variations of the exchange time induced between the core of the gel and a steady
chemical environment. This is the first synergistic actuator that operates beyond
acid-producing redox reactions.
PMID- 28425529
TI - Influence of cations in lithium and magnesium polysulphide solutions: dependence
of the solvent chemistry.
AB - In order to gain a deeper understanding of Li and Mg polysulphides in Li/S and
Mg/S batteries, respectively, this work investigates the impact of the two
different cations as well as the influence of the electrolyte solvents' relative
dielectric permittivity and Gutmann's donor number on the solubility and relative
stability of different Li and Mg polysulphide species. Therefore, the
disproportionation and dissociation equilibria of chemically prepared "Li2S8" and
"MgS8" solutions in DMSO, DMF, ACN, THF, DME, TEGDME, and Pyr14TFSI are
characterized by UV/Vis spectroscopy. Varying the cation and the solvent reveals
their mutual interplay in stabilizing different polysulphide species. To our
knowledge, this is the first time that chemically synthesized Mg polysulphides in
solutions are studied. The results of this work provide essential knowledge for
further development of the economically, ecologically, and also in terms of
energy density and safety, attractive Mg/S batteries.
PMID- 28425530
TI - Interfacial interactions between CoTPP molecules and MgO(100) thin films.
AB - We have investigated the interactions between cobalt(ii)-tetraphenylporphyrin
(CoTPP) molecules and MgO(100) thin films on Ag(100) by means of Synchrotron
Radiation X-Ray and Ultra-Violet Photoelectron Spectroscopy (SR-XPS and SR-UPS).
At room temperature, the CoTPP monolayer consists of two different species. A
minority of molecules exhibits a strong electronic interaction with the
substrate, whereas for the majority a similar spectroscopic signature as for
multilayer molecules is observed. Based on the lateral inhomogeneity of the
surface electronic structure, we tentatively suggest that the strongly
interacting molecules adsorb with their metal center directly above oxygen ions.
Unlike for metal substrates, where a monolayer can be prepared upon heating to
above 500 K, most of the monolayer on MgO desorbs at 550 K together with the
multilayers. This indicates either a weaker molecule-substrate bond than for most
metal surfaces or a higher activation energy barrier for dehydrogenation. The
remaining molecules are presumably MgTPP molecules, originating from a 2HTPP
impurity in CoTPP.
PMID- 28425531
TI - Iridium-catalysed asymmetric allylic alkylation of benzofuran gamma-lactones
followed by heteroaromatic Cope rearrangement: study of an unusual reaction
sequence.
AB - The iridium-catalysed asymmetric allylic alkylation of gamma-lactones produces an
all-carbon quaternary stereocentre substituted by an allyl and a benzofuran. The
resulting 1,5-hexadienes were found to be excellent substrates for an unusual
heteroaromatic Cope rearrangement. We describe here the first insight into the
synthetic outcome of this intriguing reaction sequence.
PMID- 28425532
TI - Emerging tellurium nanostructures: controllable synthesis and their applications.
AB - Tellurium (Te) is a rare element in trace amounts of about one part per billion,
comparable to that of platinum and ranked 75th in the abundance of the elements
in the earth crust. Te nanostructures, as narrow bandgap semiconductors, have
numerous potential applications in the fabrication of many modern devices. The
past decades have witnessed an explosion in new strategies for synthesizing
diverse emerging Te nanostructures with controlled compositions, sizes, shapes,
and structures. Their structure-determined nature makes functional Te
nanomaterials an attractive candidate for modern applications. This review
focuses on the synthesis and morphology control of emerging Te nanostructures and
summarizes the latest developments in the applications of Te nanostructures, such
as their use as chemical transformation templates to access a huge family of
nanowires/nanotubes, batteries, photodetectors, ion detection and removal,
element doping, piezoelectric energy harvesting, gas sensing, thermoelectric
devices and many other device applications. Various Te nanostructures with
different shapes and structures will exploit the beneficial properties associated
with their assembly process and nanofabrication. Finally, the prospects for
future applications of Te nanomaterials are summarized and highlighted.
PMID- 28425534
TI - O vacancy formation in (Pr/Gd)BaCo2O5.5 and the role of antisite defects.
AB - In search for materials for intermediate temperature solid oxide fuel cells,
(Pr/Gd)BaCo2O5.5 is investigated by first principles calculations. Antisite
defects are considered as they may modify the electronic and O diffusion
properties but are rarely studied in double perovskite oxides. Octahedrally
coordinated Co atoms are shown to realize intermediate and high spin states for
PrBaCo2O5.5 and GdBaCo2O5.5, respectively, while pyramidally coordinated Co atoms
always have high spin. It turns out that O vacancy formation is significantly
easier in PrBaCo2O5.5 than in GdBaCo2O5.5, the difference in formation energy
being hardly modified by antisite defects. While pyramidally coordinated Co atoms
are not affected, we show that the presence of antisite defects causes parts of
the octahedrally coordinated Co atoms to switch from intermediate to high spin.
PMID- 28425533
TI - Impact of lipid composition and photosensitizer hydrophobicity on the efficiency
of light-triggered liposomal release.
AB - Photo-triggerable liposomes are considered nowadays as promising drug delivery
devices due to their potential to release encapsulated drugs in a spatial and
temporal manner. In this work, we have investigated the photopermeation
efficiency of three photosensitizers (PSs), namely verteporfin, pheophorbide a
and m-THPP when incorporated into liposomes with well-defined lipid compositions
(SOPC, DOPC or SLPC). By changing the nature of phospholipids and PSs, the
illumination of the studied systems was shown to significantly alter their lipid
bilayer properties via the formation of lipid peroxides. The system efficiency
depends on the PS/phospholipid association, and the ability of the PS to
peroxidize acyl chains. Our results demonstrated the possible use of these three
clinically approved (or under investigation) PSs as potential candidates for
photo-triggerable liposome conception.
PMID- 28425536
TI - Cisplatin resistance in cell models: evaluation of metallomic and biological
predictive biomarkers to address early therapy failure.
AB - Cisplatin, one of the most extensively used metallodrugs in cancer treatment,
presents the important drawback of patient resistance. This resistance is the
consequence of different processes including those preventing the formation of
DNA adducts and/or their quick removal. Thus, a tool for the accurate detection
and quantitation of cisplatin-induced adducts might be valuable for predicting
patient resistance. To prove the validity of such an assumption, highly sensitive
plasma mass spectrometry (ICP-MS) strategies were applied to determine DNA adduct
levels and intracellular Pt concentrations. These two metal-relative parameters
were combined with an evaluation of biological responses in terms of genomic
stability (with the Comet assay) and cell cycle progression (by flow cytometry)
in four human cell lines of different origins and cisplatin sensitivities (A549,
GM04312, A2780 and A2780cis), treated with low cisplatin doses (5, 10 and 20 MUM
for 3 hours). Cell viability and apoptosis were determined as resistance
indicators. Univariate linear regression analyses indicated that quantitation of
cisplatin-induced G-G intra-strand adducts, measured 1 h after treatment, was the
best predictor for viability and apoptosis in all of the cell lines. Multivariate
linear regression analyses revealed that the prediction improved when the
intracellular Pt content or the Comet data were included in the analysis, for all
sensitive cell lines and for the A2780 and A2780cis cell lines, respectively.
Thus, a reliable cisplatin resistance predictive model, which combines the
quantitation of adducts by HPLC-ICP-MS, and their repair, with the intracellular
Pt content and induced genomic instability, might be essential to identify early
therapy failure.
PMID- 28425537
TI - Using fluorescently-labeled magnetic nanocomposites as a dual contrast agent for
optical and magnetic resonance imaging.
AB - Dual-modality imaging probes synergistically combine magnetic resonance (MR) and
fluorescence into a single nanocomposite. This promising technique affords a new
level of flexibility for molecular imaging uses in biomedical research. In this
study, we report a new strategy for the synthesis of a novel attapulgite nanorod
based atta@Fe3O4@[Ru(bpy)2(fmp)]Cl2 nanocomposite (atta@Fe3O4@Ru NC). Our
synthesized NC has both photoluminescent and magnetic properties, bright
fluorescence, as well as significant magnetic resonance. Transmission electron
microscopy, energy dispersive spectroscopy, fluorescence spectrometry, and
magnetization measurements were all used to validate its properties. In vitro
studies showed that our functionalized NC had high cellular biocompatibility and
was successfully used to label living cells through endocytosis of cells.
Moreover, a CCK8 assay showed that even high concentrations of the atta@Fe3O4@Ru
NC had low toxicity. Finally, the intravenous administration of the atta@Fe3O4@Ru
NC to a rabbit model of hepatic carcinoma resulted in a marked and negatively
enhanced T2-weighted MRI in both normal liver and tumor, which can further
enhance the visibility of the liver cancer tissue and normal liver tissue.
Collectively, these results suggest that the atta@Fe3O4@Ru NC can be used for
tumor discovery and diagnosis.
PMID- 28425538
TI - UV-induced hydrogen-atom transfer and hydrogen-atom detachment in monomeric 7
azaindole isolated in Ar and n-H2 matrices.
AB - Photochemical transformations were investigated for monomers of 7-azaindole
isolated in low-temperature Ar and normal-H2 (n-H2) matrices. The most stable N1H
tautomer was the only form of the compound populated in Ar and n-H2 matrices
before any irradiation. Upon exposure of Ar matrices to UV (lambda > 270 nm)
light, two higher-energy tautomers N7H and C3H were photoproduced. Additionally,
spectral signatures of the photogenerated 7-azaindolyl radical were also found.
All of these photoproducts were experimentally observed for the first time. So
far, the N7H tautomer had been known only as a transient species, appearing upon
relaxation of photoexcited hydrogen-bonded dimers or complexes. For 7-azaindole
isolated in an n-H2 matrix and irradiated at lambda > 270 nm, only the C3H
tautomer and the 7-azaindolyl radical were photogenerated, whereas the N7H
tautomer was not photoproduced at all. The drastic dependence of photogeneration
of the N7H form on the matrix environment (solid Ar or solid n-H2) is as a
characteristic feature of a specific class of UV-induced hydrogen-atom-transfer
processes occurring in matrix-isolated heterocycles.
PMID- 28425540
TI - Chemomechanical-force-induced folding-unfolding directly controls distinct
fluorescence dual-color switching.
AB - Folding-unfolding imparts fluorescence dual color switching, thus a novel concept
to switch fluorescence between two distinct colors while avoiding traditional
bond rupturing and bond forming in photoswitching. Because folding and unfolding
minimize the wear and tear on molecular structures, the new systems have
excellent reversibility and fatigue resistance.
PMID- 28425541
TI - Photoisomerisation and light-induced morphological switching of a polyoxometalate
azobenzene hybrid.
AB - The functionalization of a spherical Keplerate-type polyoxometalate {Mo72V30}
with a cationic azobenzene surfactant has been achieved through ionic self
assembly. The photoisomerisation reaction of this complex, which emerges in a
light-triggered aggregation-disaggregation process, has been followed by 1H NMR
spectroscopy, dynamic light scattering, absorption spectroscopy and scanning
electron microscopy analyses.
PMID- 28425542
TI - Acceptor doping in the proton conductor SrZrO3.
AB - Perovskite zirconates such as SrZrO3 exhibit improved proton solubility and
conductivity when doped with trivalent cations substituting at the Zr site. In
this work, we present a detailed study of Sc and Y dopants in SrZrO3 based on
first-principles, hybrid density-functional calculations. When substituting at
the Zr site (ScZr, YZr), both dopants give rise to a single, deep acceptor level,
where the neutral impurity forms a localized hole polaron state. The epsilon(0/-)
charge transition levels are 0.60 eV and 0.58 eV above the valence-band maximum
for ScZr and YZr, respectively. Under certain growth conditions, Sc and Y will
form self-compensating donor species by substituting at the Sr site (ScSr, YSr),
and this is detrimental to proton conductivity. Due to its larger ionic radius, Y
exhibits a greater tendency than Sc to self-compensate at the Sr site. We also
investigated the proton-dopant association. The binding energy of a proton to a
negatively charged acceptor impurity is 0.41 eV for Sc and 0.31 eV for Y,
indicating that proton transport is limited by trapping at impurity sites.
PMID- 28425543
TI - In situ nuclear magnetic resonance microimaging of live biofilms in a
microchannel.
AB - Biofilms are comprised of microbial cells and an extracellular polymeric
substance (EPS) matrix that supports interactions between community members and
with the local environment. The highly hydrated EPS matrix makes the application
of many biofilm visualization techniques difficult. Hence, to better visualize
how biofilms interact with their environment, there is a need for imaging
techniques to monitor hydrated state biofilm dynamics. We employed an in situ
dynamic approach to construct label-free images of biofilms. In situ imaging was
conducted using a vacuum compatible microfluidic reactor, SALVI (System for
Analysis at the Liquid Vacuum Interface), for biofilm growth; real-time confocal
laser scanning microscopy analysis; and nuclear magnetic resonance (NMR)
microimaging and spectroscopy. We integrated SALVI microchannel fluids and live
biofilms to demonstrate in situ measurement capabilities, including velocity
mapping, diffusion coefficient mapping, relaxometry, localized spectroscopy,
relaxation times, porosity, and two- and three-dimensional imaging within the
microchannel at high spatial resolution. We monitored organic acids adjacent to
biofilms, suggesting that kinetic rate and substrate-product yield ratio studies
are possible using the SALVI microfluidic reactor for growth characterizations.
The integration of NMR microimaging studies into the SALVI platform demonstrates
that a multimodal microfluidic platform can serve as an avenue to explore complex
biological phenomena, such as biofilm attachment to surfaces, with detailed
quantitative physical and chemical mapping. The further incorporation of other
SALVI-compatible technologies, such as liquid time-of-flight secondary ion mass
spectrometry imaging, with NMR microimaging will produce a powerful correlative
approach to monitor in situ biofilm chemistry and dynamics at different spatial
scales.
PMID- 28425544
TI - In situ template synthesis of hollow nanospheres assembled from NiCo2S4@C
ultrathin nanosheets with high electrochemical activities for lithium storage and
ORR catalysis.
AB - Transition-metal sulfide hollow nanostructures have received intensive attention
in energy-related applications due to their unique structural features and high
electrochemical activities. Here, a well-designed composite of NiCo2S4@C is
successfully fabricated using a facile in situ template removal method. The
obtained composite shows unique microstructures of hollow nanospheres (~650 nm in
diameter) assembled from ultrathin NiCo2S4@C nanosheets, in which numerous
scattered NiCo2S4 nanoparticles are embedded in ultrathin carbon nanosheets,
exhibiting mesoporous features with a high surface area of 247.25 m2 g-1. When
used as anode materials for LIBs, NiCo2S4@C hollow nanospheres exhibit a high
reversible capacity of 1592 mA h g-1 at a current density of 500 mA g-1, enhanced
cycling performance maintaining a capacity of 1178 mA h g-1 after 200 cycles, and
a remarkable rate capability. Meanwhile, the hollow nanospheres display excellent
catalytic activity as ORR catalysts with a four-electron pathway and superior
durability to that of commercial Pt/C catalysts. Their excellent lithium storage
and ORR catalysis performance can be attributed to the rational incorporation of
high-activity NiCo2S4 and ultrathin carbon nanosheets, as well as unique hollow
microstructures, which offer efficient electron/ion transport, an enhanced
electroactive material/electrolyte contact area, numerous active sites, and
excellent structural stability.
PMID- 28425545
TI - Beware of phosphate: evidence of specific dendrimer-phosphate interactions.
AB - Dendrimers are extensively studied for drug delivery and catalysis, most of which
are pH dependent. Phosphate buffer solutions (PBSs) are often used to adjust the
pH. We have found that phosphate ions become incorporated into poly(amidoamine)
(PAMAM) dendrimer molecules by forming H-bonds with tertiary nitrogens. We show
that this specific interaction between H2PO4- and HPO42- ions and generation five
PAMAM dendrimers causes a decrease in hydrodynamic size, disturbing the outcome
of the size exclusion chromatography analysis. We monitored this interaction by
1H and 31P high resolution NMR, NMR-diffusiometry, pH-potentiometry and infrared
spectroscopy. Failing to take into account this effect may lead to incorrect
conclusions and misinterpreting interactions of PAMAM dendrimers with drug
molecules and subsequently incorrect dosing. The phosphate salts of amino
terminated generation five PAMAM dendrimers are stable for years when stored in
the dark, even in dilute aqueous solutions, which has important implications for
the shelf-life of dendrimer-based drug delivery systems.
PMID- 28425548
TI - Emission behaviours of novel V- and X-shaped fluorophores in response to pH and
force stimuli.
AB - A family of novel fluorophores with V- and X-shaped skeletons is rationally
designed and prepared. Due to the extended cross pi-conjugation in the X-shaped
ones, their emission wavelengths in both solution and the solid state exhibit
considerable bathochromic shifts compared with those of the V-shaped ones. It is
found that a heavy intramolecular charge transfer (ICT) effect is the primary
element for the mechanofluorochromic (MFC) response of this family, and an
appropriate crystallinity of the sample is also indispensible for it to be MFC
active. Additionally, most fluorophores in this family are responsive to pH
stimuli and display diverse and reversible changes of emission features.
Interestingly, a V-shaped fluorophore exhibits a unique size-dependent emission
behaviour, which makes it a distinctive three-color emitter.
PMID- 28425546
TI - Variable coordination of tris(2-pyridyl)phosphine and its oxide toward M(hfac)2:
a metal-specifiable switching between the formation of mono- and bis-scorpionate
complexes.
AB - An unexpected substitution of the anionic chelating ligands at the MII centre by
a neutral tripodal ligand has been observed in the reaction of MnII, CoII, NiII
and CuII hexafluoroacetylacetonates (hfac) with tris(2-pyridyl)phosphine (Py3P)
or its oxide (Py3P = O). The nature of the metal ion in M(hfac)2 and the M/L
ratio determine the degree of substitution of hfac-anions (partial vs. total) and
therefore, the structure of the complex formed (scorpionate vs. bis-scorpionate
ones, respectively). Hence, the reaction of the ligands with [Cu(hfac)2(H2O)2] in
an equimolar ratio affords scorpionate [Cu(N,N',N''-Py3P = X)(O,O'-hfac)(O
hfac)], wherein one hfac-ligand chelates metal, while the other hfac acts as an O
monodentate one. Using the two equivalents of Py3P in this reaction leads to
[Cu(N,N',N''-Py3P)2](hfac)2, which contains a bis-scorpionate cation
[Cu(Py3P)2]2+ and two noncoordinated hfac-anions. [Co(hfac)2(H2O)2] and
[Ni(hfac)2(H2O)2], regardless of the M/L molar ratio, react with Py3P = O to give
cationic scorpionates [M(N,N',N''-Py3P = O)(O,O'-hfac)(H2O)](hfac), in which one
hfac-anion is noncoordinated. In contrast, [Mn(hfac)2(H2O)2], on interaction with
Py3P, results in the cationic complex [Mn(N,N',N''-Py3P)2][Mn(hfac)3]2 bearing a
bis-scorpionate cation [Mn(Py3P)2]2+ and two [Mn(hfac)3]2- counterions. The
synthesized scorpionates have been characterized by X-ray diffractometry, cyclic
voltammetry, SQUID magnetometry, FT-IR and UV-Vis techniques.
PMID- 28425549
TI - Nicotinamide adenine dinucleotide detection based on silver nanoclusters
stabilized by a dumbbell-shaped probe.
AB - We have developed a novel method for detecting nicotinamide adenine dinucleotide
(NAD+) based on fluorescent silver nanoclusters (AgNCs) stabilized by a dumbbell
shaped DNA template containing two cytosine-loops joined in a dsDNA stem. The
design involves two types of components: a dumbbell-shaped DNA template and three
enzymes. In the presence of NAD+ as a cofactor, Escherichia coli DNA ligase
(E.coli DNA ligase) catalyzes template ligation to generate a sealed (no terminal
nucleotides) dumbbell-shaped structure, preventing digestion by exonuclease III
(Exo III) and exonuclease I (Exo I). The loop regions of the intact template
serve as sites for the deposition of highly fluorescent AgNCs. In the absence of
NAD+, the ligation reaction does not occur, and the unsealed dumbbell-shaped
template is digested into mononucleotides via cooperation of Exo III and Exo I.
The destruction of the DNA template results in the agglomeration of AgNCs into
silver nanoparticles with low fluorescence. The fluorescence enhancement depends
on the ligation and digestion of the DNA template, allowing quantitative
detection of NAD+ in the range of 0.5 nM-5000 nM with a detection limit of ~0.25
nM.
PMID- 28425550
TI - Site-selective carbon-carbon bond formation in unprotected monosaccharides using
photoredox catalysis.
AB - Site-selective photoredox reactions with somophiles readily enable branching of
the carbon skeleton of unprotected glucosides, allosides, and xylosides
regioselectively at C3. These reactions open the possibility of selective C-C
bond formation in monosaccharides without multi-step protection-deprotection
strategies.
PMID- 28425551
TI - Synthesis and characterization of a dipyriamethyrin-uranyl complex.
AB - The reaction between non-aqueous uranyl silylamide (UO2[N(SiMe3)2]2.2THF) under
anaerobic conditions or uranyl acetate (UO2(OAc)2.2H2O) under standard laboratory
conditions and dipyriamethryin affords a bench-stable uranyl complex. Competition
studies as well as DFT calculations provide support for the observed selectivity
for the uranyl cation over trivalent lanthanide and multiple transition metal
precursors.
PMID- 28425552
TI - The effect of chemical ordering and lattice mismatch on structural transitions in
phase segregating nanoalloys.
AB - We elucidate the effect of lattice mismatch and chemical ordering on structural
transitions in bimetallic nanoalloys of ~1.5 nm. We show that collective screw
dislocation motions happen in small mismatch shell@core systems while strongly
mismatched ones favour incomplete outer shell rearrangements. Cooperative
transitions can also become hindered when the chemical ordering breaks the
geometrical symmetry. Escaping from an unfavourable morphological basin occurs
first via re-arrangements of the geometry and then changes towards a better
chemical pattern. We observe that the chemical re-ordering mechanisms are
independent of system composition and stoichiometry but hinge on the initial and
final chemical arrangements.
PMID- 28425553
TI - Structural control of side-chain chromophores to achieve highly efficient electro
optic activity.
AB - A series of chromophores J1-J4 have been synthesized based on julolidine donors
modified with different rigid steric hindrance groups. Compared with the
chromophore (J1) without the isolation group, chromophores J2, J3 and J4 show
better stability. Structural analysis and photophysical property measurements
were carried out to compare the molecular mobility and steric hindrance effect of
the different donor-modified chromophores. All of these chromophores with
isolation groups showed superb thermal stabilities with high thermal
decomposition temperatures above 250 degrees C. Furthermore, with rigid steric
hindrance, chromophores J3 and J4 showed more enhanced thermal stabilities with
thermal decomposition temperatures of 269 degrees C and 275 degrees C,
respectively. Density functional theory was used to calculate the
hyperpolarizability (beta), and the high molecular hyperpolarizability of these
chromophores can be effectively translated into large electro-optic coefficients.
The electro-optic coefficients of poled films containing 20 wt% of these new
chromophores doped in amorphous polycarbonate were 127, 266 and 209 pm V-1 at
1310 nm for chromophores J1-J3, respectively, while the film containing
chromophore J4 showed the largest r33 value of only 97 pm V-1 at 25 wt%. These
results indicated that the introduced isolation group can reduce intermolecular
electrostatic interactions, thus enhancing the macroscopic electro-optic
activity, while the size of the isolation group should be suitable.
PMID- 28425554
TI - On the parallelism between the mechanisms behind chromatography and drug
delivery: the role of interactions with a stationary phase.
AB - A huge number of studies and work in the drug delivery literature are focused on
understanding and modeling transport phenomena, the pivotal point for a good
device design. The rationalization of all phenomena involved is fundamental, but
several concerns arise leaving many issues unsolved. In order to change the point
of view we decided to focus our attention on the parallelisms between two fields
that seem to be very far from each other: chromatography and drug release. Taking
advantages of the studies conducted by many researchers using chromatographic
columns we decided to explain all the phenomena involved in drug delivery
considering sodium ibuprofen (IP) molecules as analytes and hydrogel as a
stationary phase. In particular, we considered not only diffusion, but also drug
polymer interactions as adsorption on the stationary phase and drug-drug
interactions as aggregation of analytes. The hydrogel investigated is a promising
formulation made of agarose and carbomer 974p (AC) loaded with IP, a non
steroidal common anti-inflammatory drug. The self-diffusion coefficient of IP in
AC formulations was measured by using an innovative method based on a magic angle
spinning NMR spectroscopic technique to produce high resolution (liquid-like)
spectra. This method (HR-MAS NMR) is used in combination with pulsed field
gradient spin echo (PGSE) liquid-state techniques. The model predictions
satisfactorily match with the experimental data obtained in water and the gel
environment, indicating that the model presented here, despite its simplicity, is
able to describe the key phenomena governing the device behavior and could be
used to rationalize the experimental activity.
PMID- 28425555
TI - Electrochemical reduction of CO2 on graphene supported transition metals -
towards single atom catalysts.
AB - In this study, we have investigated the use of single metal atoms supported on
defective graphene as catalysts for the electrochemical reduction of CO2 using
the first-principles approach and the computational hydrogen electrode model.
Reaction pathways to produce a variety of C1 products CO, HCOOH, HCHO, CH3OH and
CH4 have been studied in detail for five representative transition metals Ag, Cu,
Pd, Pt, and Co. Different pathways were revealed in contrast to those found for
metallic crystalline surfaces and nanoparticles. These single atom catalysts have
demonstrated a general improvement in rate limiting potentials to generate C1
hydrocarbons. They also show distinct differences in terms of their efficiency
and selectivity in CO2 reduction, which can be correlated with their elemental
properties as a function of their group number in the periodic table. Six best
candidates for CH4 production are identified by conducting computational
screening of 28 d-block transition metals. Ag has the lowest overpotential (0.73
V), and is followed by Zn, Ni, Pd, Pt and Ru with overpotentials all below 1 V.
Cu in the supported single atom form shows a strong preference towards producing
CH3OH with an overpotential of 0.68 V well below the value of 1.04 V for
producing CH4.
PMID- 28425557
TI - Dual spectra band emissive Eu2+/Mn2+ co-activated alkaline earth phosphates for
indoor plant growth novel phosphor converted-LEDs.
AB - This paper reports designing a novel single composition blue/red color
illuminating phosphor followed by fabricating "smart" agricultural/horticultural
LED lighting. Color-tunable Eu2+/Mn2+ co-activated alkaline earth phosphates,
Na(Sr,Ba)PO4 and Ca3Mg3(PO4)4, are considered, and the stable doping sites for
the corresponding activators are identified by using first-principle DFT
calculations. We can realize the designated color purity with stable thermal
quenching preserved luminescence behavior is induced by the Eu2+ center
positioned at different coordination states with intermixed Sr2+/Ba2+ sites in
Na(Sr,Ba)PO4 hosts. Moreover, we demonstrate that the resultant LED lighting
adopting the proposed novel phosphor composition stimulates the enhanced
photosynthesis reaction for indoor hydroponics plants, such as oats and onions,
which is superior to the narrow line emission band induced by the mixture of
conventional red/green/blue LEDs. Thus, using the color-tunable single
composition luminescent material may produce an innovative energy-efficient
artificial lighting for indoor plant growth.
PMID- 28425558
TI - Real-time temperature monitoring with fiber Bragg grating sensor during diffuser
assisted laser-induced interstitial thermotherapy.
AB - High-sensitivity temperature sensors have been used to validate real-time thermal
responses in tissue during photothermal treatment. The objective of the current
study was to evaluate the feasible application of a fiber Bragg grating (FBG)
sensor for diffuser-assisted laser-induced interstitial thermotherapy (LITT)
particularly to treat tubular tissue disease. A 600 - ? m core-diameter diffuser
was employed to deliver 980-nm laser light for coagulation treatment. Both a
thermocouple and a FBG were comparatively tested to evaluate temperature
measurements in ex vivo liver tissue. The degree of tissue denaturation was
estimated as a function of irradiation times and quantitatively compared with
light distribution as well as temperature development. At the closer distance to
a heat source, the thermocouple measured up to 41% higher maximum temperature
than the FBG sensor did after 120-s irradiation (i.e., 98.7 degrees C +/- 6.1
degrees C for FBG versus 131.0 degrees C +/- 5.1 degrees C for thermocouple;
p < 0.001 ). Ex vivo porcine urethra tests confirmed the real-time temperature
measurements of the FBG sensor as well as consistently circumferential tissue
denaturation after 72-s irradiation ( coagulation thickness = 2.2 +/- 0.3 ?? mm
). The implementation of FBG can be a feasible sensing technique to
instantaneously monitor the temperature developments during diffuser-assisted
LITT for treatment of tubular tissue structure.
PMID- 28425559
TI - Multimodal optical setup based on spectrometer and cameras combination for
biological tissue characterization with spatially modulated illumination.
AB - The application of optical techniques as tools for biomedical research has
generated substantial interest for the ability of such methodologies to
simultaneously measure biochemical and morphological parameters of tissue.
Ongoing optimization of optical techniques may introduce such tools as
alternative or complementary to conventional methodologies. The common approach
shared by current optical techniques lies in the independent acquisition of
tissue's optical properties (i.e., absorption and reduced scattering
coefficients) from reflected or transmitted light. Such optical parameters, in
turn, provide detailed information regarding both the concentrations of
clinically relevant chromophores and macroscopic structural variations in tissue.
We couple a noncontact optical setup with a simple analysis algorithm to obtain
absorption and scattering coefficients of biological samples under test.
Technically, a portable picoprojector projects serial sinusoidal patterns at low
and high spatial frequencies, while a spectrometer and two independent CCD
cameras simultaneously acquire the reflected diffuse light through a single
spectrometer and two separate CCD cameras having different bandpass filters at
nonisosbestic and isosbestic wavelengths in front of each. This configuration
fills the gaps in each other's capabilities for acquiring optical properties of
tissue at high spectral and spatial resolution. Experiments were performed on
both tissue-mimicking phantoms as well as hands of healthy human volunteers to
quantify their optical properties as proof of concept for the present technique.
In a separate experiment, we derived the optical properties of the hand skin from
the measured diffuse reflectance, based on a recently developed camera model.
Additionally, oxygen saturation levels of tissue measured by the system were
found to agree well with reference values. Taken together, the present results
demonstrate the potential of this integrated setup for diagnostic and research
applications.
PMID- 28425560
TI - Impact of simulated three-dimensional perception on precision of depth
judgements, technical performance and perceived workload in laparoscopy.
AB - BACKGROUND: This study compared precision of depth judgements, technical
performance and workload using two-dimensional (2D) and three-dimensional (3D)
laparoscopic displays across different viewing distances. It also compared the
accuracy of 3D displays with natural viewing, along with the relationship between
stereoacuity and 3D laparoscopic performance. METHODS: A counterbalanced within
subjects design with random assignment to testing sequences was used. The system
could display 2D or 3D images with the same set-up. A Howard-Dolman apparatus
assessed precision of depth judgements, and three laparoscopic tasks (peg
transfer, navigation in space and suturing) assessed performance (time to
completion). Participants completed tasks in all combinations of two viewing
modes (2D, 3D) and two viewing distances (1 m, 3 m). Other measures administered
included the National Aeronautics and Space Administration Task Load Index
(perceived workload) and the Randot(r) Stereotest (stereoacuity). RESULTS: Depth
judgements were 6.2 times as precise at 1 m and 3.0 times as precise at 3 m using
3D versus 2D displays (P < 0.001). Participants performed all laparoscopic tasks
faster in 3D at both 1 and 3 m (P < 0.001), with mean completion times up to 64
per cent shorter for 3D versus 2D displays. Workload was lower for 3D displays
(up to 34 per cent) than for 2D displays at both viewing distances (P < 0.001).
Greater viewing distance inhibited performance for two laparoscopic tasks, and
increased perceived workload for all three (P < 0.001). Higher stereoacuity was
associated with shorter completion times for the navigating in space task
performed in 3D at 1 m (r = - 0.40, P = 0.001). CONCLUSION: 3D displays offer
large improvements over 2D displays in precision of depth judgements, technical
performance and perceived workload.
PMID- 28425561
TI - Creating homogenous strain distribution within 3D cell-encapsulated constructs
using a simple and cost-effective uniaxial tensile bioreactor: Design and
validation study.
AB - Mechanical loading bioreactors capable of applying uniaxial tensile strains are
emerging to be a valuable tool to investigate physiologically relevant cellular
signaling pathways and biochemical expression. In this study, we have introduced
a simple and cost-effective uniaxial tensile strain bioreactor for the
application of precise and homogenous uniaxial strains to 3D cell-encapsulated
collagen constructs at physiological loading strains (0-12%) and frequencies
(0.01-1 Hz). The bioreactor employs silicone-based loading chambers specifically
designed to stretch constructs without direct gripping to minimize stress
concentration at the ends of the construct and preserve its integrity. The
loading chambers are driven by a versatile stepper motor ball-screw actuation
system to produce stretching of the constructs. Mechanical characterization of
the bioreactor performed through Finite Element Analysis demonstrated that the
constructs experienced predominantly uniaxial tensile strain in the longitudinal
direction. The strains produced were found to be homogenous over a 15 * 4 * 2 mm
region of the construct equivalent to around 60% of the effective region of
characterization. The strain values were also shown to be consistent and
reproducible during cyclic loading regimes. Biological characterization confirmed
the ability of the bioreactor to promote cell viability, proliferation, and
matrix organization of cell-encapsulated collagen constructs. This easy-to-use
uniaxial tensile strain bioreactor can be employed for studying morphological,
structural, and functional responses of cell-embedded matrix systems in response
to physiological loading of musculoskeletal tissues. It also holds promise for
tissue-engineered strategies that involve delivery of mechanically stimulated
cells at the site of injury through a biological carrier to develop a clinically
useful therapy for tissue healing. Biotechnol. Bioeng. 2017;114: 1878-1887. (c)
2017 Wiley Periodicals, Inc.
PMID- 28425562
TI - Couples with Intimate Partner Violence Seeking Relationship Help: Associations
and Implications for Self-Help and Online Interventions.
AB - In-person conjoint treatments for relationship distress are effective at
increasing relationship satisfaction, and newly developed online programs are
showing promising results. However, couples reporting even low levels intimate
partner violence (IPV) are traditionally excluded from these interventions. To
improve the availability of couple-based treatment for couples with IPV, the
present study sought to determine whether associations with IPV found in
community samples generalized to couples seeking help for their relationship and
whether web-based interventions for relationship distressed worked equally well
for couples with IPV. In the first aim, in a sample of 2,797 individuals who were
seeking online help for their relationship, the levels and correlates of both low
intensity and clinically significant IPV largely matched what is found in
community samples. In the second aim, in a sample of 300 couples who were
randomly assigned to a web-based intervention or a waitlist control group, low
impact IPV did not moderate the effects of the intervention for relationship
distress. Therefore, web-based interventions may be an effective (and easily
accessible) intervention for relationship distress for couples with low-intensity
IPV.
PMID- 28425563
TI - Differences in interregional brain connectivity in children with unilateral
hearing loss.
AB - OBJECTIVES: To identify functional network architecture differences in the brains
of children with unilateral hearing loss (UHL) using resting-state functional
connectivity magnetic resonance imaging (rs-fcMRI). STUDY DESIGN: Prospective
observational study. METHODS: Children (7 to 17 years of age) with severe to
profound hearing loss in one ear, along with their normal hearing (NH) siblings,
were recruited and imaged using rs-fcMRI. Eleven children had right UHL; nine had
left UHL; and 13 had normal hearing. Forty-one brain regions of interest culled
from established brain networks such as the default mode (DMN); cingulo-opercular
(CON); and frontoparietal networks (FPN); as well as regions for language,
phonological, and visual processing, were analyzed using regionwise correlations
and conjunction analysis to determine differences in functional connectivity
between the UHL and normal hearing children. RESULTS: When compared to the NH
group, children with UHL showed increased connectivity patterns between multiple
networks, such as between the CON and visual processing centers. However, there
were decreased, as well as aberrant connectivity patterns with the coactivation
of the DMN and FPN, a relationship that usually is negatively correlated.
CONCLUSION: Children with UHL demonstrate multiple functional connectivity
differences between brain networks involved with executive function, cognition,
and language comprehension that may represent adaptive as well as maladaptive
changes. These findings suggest that possible interventions or habilitation,
beyond amplification, might be able to affect some children's requirement for
additional help at school. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2636-2645,
2017.
PMID- 28425565
TI - Immunolocalization of Jian Carp (Cyprinus Carpio Var. Jian) Cathepsin B: Cloning,
Expression, Characterization, and Antibody Preparation.
AB - Cathepsin B (CatB) cDNA of 759 bp from Jian carp (Cyprinus carpio var. Jian) with
amino acid similarity of 99.6% to common carp was cloned. The mature CatB was
expressed in Escherichia coli BL21 transferred with vector CatB-pET-30a. It was
purified and identified as a single band (29 kDa) on SDS-PAGE. Optimum CatB
activity was observed at 40 degrees C and pH 5.5. Mouse anti-CatB polyclonal
antibody with a high titer of 1:256000 was prepared successfully and shown to
specifically recognize the antigen both in prokaryotic cells and in the tissues
of Jian carp according to western blotting and immunohistochemistry results.
Immunolocation analysis showed that CatB distribution at protein level varied
among the tested tissues. The results presented in this study may provide a
significant reference for future research on the inherent relationship between
CatB and the quality of fish or fish products at both the gene and protein
levels.
PMID- 28425564
TI - Osteoblast role in osteoarthritis pathogenesis.
AB - Even if osteoarthritis pathogenesis is still poorly understood, numerous
evidences suggest that osteoblasts dysregulation plays a key role in
osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been
described in osteoarthritis osteoblasts, which is responsible for abnormal bone
remodeling and decreased mineralization. Alterations in genes expression are
involved in dysregulation of osteoblast function, bone remodeling, and
mineralization, leading to osteoarthritis development. Moreover, osteoblasts
produce numerous transcription factors, growth factors, and other proteic
molecules which are involved in osteoarthritis pathogenesis.
PMID- 28425566
TI - Gender-specific histopathological response in guppies Poecilia reticulata exposed
to glyphosate or its metabolite aminomethylphosphonic acid.
AB - Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid
(AMPA) was investigated in guppies, Poecilia reticulata. We tested the effects of
these chemicals on the gills and liver of both male and female guppies using
qualitative and quantitative histopathological analyses associated with
histopathological condition indexes. Both genders showed similar median lethal
concentration (LC50 ) at 96 h for GLY (68.78 and 70.87 mg l-1 ) and AMPA (180 and
164.32 mg l-1 ). However, the histopathological assessment of both fish organs
exposed to sublethal concentrations of GLY (35 mg l-1 ) and AMPA (82 mg l-1 ) for
96 h showed a tissue- and gender-specific histopathological response. In both
exposure assays, fish presented mainly progressive changes, such as proliferation
of the interlamellar epithelium, partial and total fusion of secondary lamellae.
The liver showed mainly regressive changes, such as steatosis, pyknotic nuclei
and high distribution of collagen fibers. Unusually large hepatocytes as
degenerated cells were also detected. Histopathological changes in gills were
similar for the males and females, but the liver response was different between
the genders. The hepatic inflammatory changes were more common in males. The
increase in the area of hepatocyte vacuoles is gender dependent with higher
values in the male compared to the female guppies exposed to GLY and AMPA.
Multiparametric analysis indicated that the male guppies are more sensitive than
females, particularly in the presence of AMPA. Our study shows that the
histopathological assessment associated with gender-specific response can be
successfully used in ecotoxicological assessment of GLY and the metabolite AMPA.
Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425567
TI - Effect of NGF From Venom of Chinese Cobra (Naja Atra)on Chondrocytes
Proliferation and Metabolism In Vitro.
AB - Autologous chondrocyte implantation (ACI) is promising strategy for cartilage
repair. However, chondrocyte phenotype is easily lost when expanded in vitro
which defined as "dedifferentiation." To ensure successful therapy, an effective
pro-chondrogenic agent is necessary to overcome the obstacle of limited cell
numbers in the restoration process, and dedifferentiation is a prerequisite. In
the present study, we investigated the chondro-protective effect of NGF from
Chinese cobra venom on human chondrocytes by determination of its specific effect
on cell viability, proliferation, morphology, GAG production, and cartilage
specific gene expression. The results suggested that NGF showed no cytotoxicity
to chondrocytes below the concentration of 16 ug/mL. DNA and glycosaminoglycan
(GAG) content were, respectively, improved in NGF groups comparing to the control
(P < 0.05). NGF up-regulate the gene expression of ACAN, SOX9, and COL2A1 while
down-regulate the expression level of COL1A1 (P < 0.05). Moreover, the results of
viability assay, hematoxylin-eosin, safranin O, and immunohistochemical staining
also suggested better performances in NGF groups. NGF of 6 ug/mL shown lower
cytotoxicity on chondrocytes, more glycosaminoglycans (GAGs) synthesis and up
regulated chondrogenic gene expression. This study may provide a basis for the
development of a novel agent for the treatment of articular cartilage defects. J.
Cell. Biochem. 118: 4308-4316, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425568
TI - libKEDF: An accelerated library of kinetic energy density functionals.
AB - Kinetic energy density functionals (KEDFs) approximate the kinetic energy of a
system of electrons directly from its electron density. They are used in
electronic structure methods that lack direct access to orbitals, for example,
orbital-free density functional theory (OFDFT) and certain embedding schemes. In
this contribution, we introduce libKEDF, an accelerated library of modern KEDF
implementations that emphasizes nonlocal KEDFs. We discuss implementation details
and assess the performance of the KEDF implementations for large numbers of
atoms. We show that using libKEDF, a single computing node or (GPU) accelerator
can provide easy computational access to mesoscale chemical and materials science
phenomena using OFDFT algorithms. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425569
TI - A Comparative Study of Natural Antimicrobial Delivery Systems for Microbial
Safety and Quality of Fresh-Cut Lettuce.
AB - Nanoencapsulation can provide a means to effectively deliver antimicrobial
compounds and enhance the safety of fresh produce. However, to date there are no
studies which directly compares how different nanoencapsulation systems affect
fresh produce safety and quality. This study compared the effects on quality and
safety of fresh-cut lettuce treated with free and nanoencapsulated natural
antimicrobial, cinnamon bark extract (CBE). A challenge study compared
antimicrobial efficacy of 3 different nanoencapsulated CBE systems. The most
effective antimicrobial treatment against Listeria monocytogenes was chitosan-co
poly-N-isopropylacrylamide (chitosan-PNIPAAM) encapsulated CBE, with a reduction
on bacterial load up to 2 log10 CFU/g (P < 0.05) compared to the other
encapsulation systems when fresh-cut lettuce was stored at 5 degrees C and 10
degrees C for 15 d. Subsequently, chitosan-PNIPAAM-CBE nanoparticles (20, 40, and
80 mg/mL) were compared to a control and free CBE (400, 800, and 1600 MUg/mL) for
its effects on fresh-cut lettuce quality over 15 d at 5 degrees C. By the 10th
day, the most effective antimicrobial concentration was 80 mg/mL for chitosan
PNIPAAM-CBE, up to 2 log10 CFU/g reduction (P < 0.05), compared with the other
treatments. There was no significant difference between control and treated
samples up to day 10 for the quality attributes evaluated. Chitosan-PNIPAAM-CBE
nanoparticles effectively inhibited spoilage microorganisms' growth and extended
fresh-cut lettuce shelf-life. Overall, nanoencapsulation provided a method to
effectively deliver essential oil and enhanced produce safety, while creating
little to no detrimental quality changes on the fresh-cut lettuce.
PMID- 28425570
TI - Elongation of barley roots in high-pH nutrient solution is supported by both cell
proliferation and differentiation in the root apex.
AB - Many crops grow well on neutral or weakly acidic soils. The ability of roots to
elongate under high-external pH would be advantageous for the survival of plants
on alkaline soil. We found that root elongation was promoted in some plant
species in alkaline-nutrient solution. Barley, but not tomato, root growth was
maintained in pH 8 nutrient solution. Fe and Mn were absorbed well from the pH 8
nutrient solution by both barley and tomato plants, suggesting that the different
growth responses of these two species may not be caused by insolubilization of
transition metals. The ability of intact barley and tomato plants to acidify
external solution was comparable; in both species, this ability decreased in
plants exposed to pH 8 nutrient solution for 1 w. Conversely, cell proliferation
and elongation in barley root apices were facilitated at pH 8 as shown by
microscopy and cell-cycle-related gene-expression data; this was not observed in
tomato. We propose that barley adapts to alkaline stress by increasing root
development.
PMID- 28425572
TI - Increased propionate concentration in Lactobacillus mucosae fermented wet brewers
grains and during in vitro rumen fermentation.
AB - AIMS: This study was conducted to isolate and identify propionate-producing
bacteria that can be used as an inoculum in improving wet brewers grains and
rumen fermentation via increasing propionate concentration. METHODS AND RESULTS:
A strain of Lactobacillus that exhibits high levels of propionate production was
identified and characterized as Lactobacillus mucosae 521129 by 16S rRNA gene
sequencing and phylogenetic analyses. Wet brewers grains were fermented through
L. mucosae inoculation and resulted in an increase in propionate concentration.
Fermented wet brewers grains were used in in vitro rumen fermentation and
revealed that L. mucosae-fermented wet brewers grains produced more gas and had
higher accumulations propionate, and total VFA than the control. The fewest
methanogen DNA copies were detected in L. mucosae fermented wet brewers grains.
CONCLUSION: Identified L. mucosae improved the fermentation of wet brewers grains
and the in vitro rumen fermentation via increasing propionate and total VFA
concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented research
provided the identification of L. mucosae 521129 as a propionate producer and was
metabolically profiled. Furthermore, data present the putative application of
this organism in improving the fermentation of wet brewers grains and in vitro
rumen fermentation. This article is protected by copyright. All rights reserved.
PMID- 28425571
TI - Clinical factors affecting costs in patients receiving systemic antifungal
therapy in intensive care units in Greece: Results from the ESTIMATOR study.
AB - : Invasive fungal infections are common in intensive care units (ICUs) but there
is a great variability in factors affecting costs of different antifungal
treatment strategies in clinical practice. To determine factors affecting
treatment cost in adult ICU patients with or without documented invasive fungal
infection receiving systemic antifungal therapy (SAT) we have performed a
prospective, multicentre, observational study enrolling patients receiving SAT in
participating ICUs in Greece. During the study period, 155 patients received SAT
at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment
began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre
emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to
have proven infection with Candida spp. (eight while on treatment). The most
frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole
(31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by
SAT strategy was ?20 458 (proven), ?15 054 (prophylaxis), ?23 594 (empiric) and
?22 184 (pre-emptive). Factors associated with significantly increased cost were
initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e.
from admission until treatment start), fever and proven candidaemia (all P<=.05).
CONCLUSION: Early administration of antifungal drugs was not a substantial
component of total hospital costs. However, there was a significant adverse
impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis
of fungaemia was delayed before starting SAT, and with initial treatment failure.
Awareness of potential candidaemia and initiation of pre-emptive or empirical
strategy as early appropriate treatment may improve ICU patient outcomes while
reducing direct medical costs.
PMID- 28425573
TI - Evaluation of Australian dermatological postoperative patient information
leaflets: Should we have a national checklist?
AB - BACKGROUND/OBJECTIVES: Patient information leaflets (PILs) are frequently
provided to patients following dermatological surgery to provide advice and
reassurance in the community. This evaluation reviewed the guidance specified in
postoperative PILs across the 40 Australian dermatology teaching departments and
clinics. METHODS: All 40 departments and clinics were identified and asked to
provide their postoperative information leaflets on sutured wound care
(preferable) or excision biopsy (September-October 2015). For each PIL, 10
preselected parameters were evaluated. RESULTS: In total, 28/40 (70%) of units
responded. From these units, 11/28 (39.3%) stated they do not use a postoperative
PIL. Of the 17 units that provided PILs, the mode minimum dressing duration was
24 (6/17; 35.3%) and 48 h (6/17; 35.3%). For haemostatic advice, 12 PILs
specified the time to press on a bleeding wound, with the most common advice
being 10 (3/12; 25%) and 20 min (3/12; 25%). Of the 14 PILs that provided
analgesic advice, the mode information suggested using paracetamol only and
avoiding aspirin (4/14, 28.6%). Two or more signs of infection were stated in
11/17 (64.7%) PILs; 7/17 (41.2%) advised applying petroleum jelly to the wound,
almost all PILs highlighted the contact for postoperative problems 16/17 (94.1%),
and 5/17 (29.4%) leaflets mentioned scarring. Altogether 8/17 (47.1%) of PILs
advised on the timeframe until active exercise could resume postoperatively.
CONCLUSION: Guidance provided in Australian postoperative dermatological PILs is
heterogeneous. A consensus checklist or template would be beneficial and ensure
that advice provided to patients is more consistent; this could be adapted for
local factors.
PMID- 28425574
TI - Factors associated with sustainability of 2 quality improvement programs after
achieving early implementation success. A qualitative case study.
AB - RATIONALE, AIMS, AND OBJECTIVES: Sustainability of innovations is a relatively
new concept in health care research and has become an issue of growing interest.
The current study explored factors related to the sustainability of 2
multidisciplinary hospital-based programs 3 to 6 years after achieving early
implementation success. METHOD: An exploratory qualitative study was conducted
into 2 implementation cases, an Enhanced Recovery After Surgery program for
colorectal surgery and a short-stay program for breast cancer surgery.
Semistructured interviews were held with key persons involved in the care process
in 14 hospitals from both cases minimally 3 years after the implementation,
between March 2012 and May 2013. The Consolidated Framework for Implementation
Research was used to direct the development of the interview guide, during data
collection and during analysis. A directed content analysis was performed.
RESULTS: A total of 21 interviews with 26 individuals were held, 18 regarding the
Enhanced Recovery After Surgery case and 8 regarding the short-stay program case.
Respondents mentioned the following factors associated with sustainability of the
programs: modification and adaptability of the program, cost-effectiveness,
institutionalization into existing systems, short communication lines within the
multidisciplinary team, an innovative culture, benefits for patients,
cosmopolitanism, the existence of external policies and incentives, trust and
belief in the program, and spread of the program to other settings. Two factors
are not covered by the Consolidated Framework for Implementation Research, ie,
modification of the program over the years and spread of the program to other
contexts. CONCLUSIONS: The factors associated with sustainability put forward in
both cases were largely the same. Leadership and the implementation project were
not mentioned as having influenced the long-term sustainability of the benefits
achieved. Sustainability of the innovations is influenced by determinants
stemming from all ecological levels of the health care system and demands
continuous effort in the postimplementation phase.
PMID- 28425575
TI - High Dose Supplementation of Vitamin D Affects Measures of Systemic Inflammation:
Reductions in High Sensitivity C-Reactive Protein Level and Neutrophil to
Lymphocyte Ratio (NLR) Distribution.
AB - The prevalence of Vitamin D deficiency is increasing worldwide, which has be
shown to be associated with increased risk of cardiovascular disease (CVD),
autoimmune disease, and metabolic syndrome. These conditions are also associated
with a heightened state of inflammation. The aim of the current study was to
evaluate the effect of vitamin D supplementation on serum C-Reactive Protein
(CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large
cohort of adolescent girls. A total of 580 adolescent girls were recruited follow
by evaluation of CRP and hematological parameters before and after
supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol
capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level
was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8
(95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g.,
NLR level was 1.66 +/- 0.72 and 1.53 +/- 0.67, P = 0.002, before and after
therapy with compliance rate of >95.2%). Moreover, we found an association
between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes.
Interestingly we observed a significant reduction in neutrophil count and CRP
level after high dose vitamin D supplementation. Our findings showed that the
high dose supplementation of vitamin D affects measures of systemic inflammation:
reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to
lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. (c)
2017 Wiley Periodicals, Inc.
PMID- 28425576
TI - Bone Marrow, Adipose, and Lung Tissue-Derived Murine Mesenchymal Stromal Cells
Release Different Mediators and Differentially Affect Airway and Lung Parenchyma
in Experimental Asthma.
AB - Mesenchymal stromal cells (MSCs) from different sources have differential effects
on lung injury. To compare the effects of murine MSCs from bone marrow (BM),
adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling
processes in experimental allergic asthma, female C57BL/6 mice were sensitized
and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the
last challenge, mice received either saline (50 ul, SAL), BM-MSCs, AD-MSCs, or
LUNG-MSCs (105 cells per mouse in 50 ul total volume) intratracheally. At 1 week,
BM-MSCs produced significantly greater reductions in resistive and viscoelastic
pressures, bronchoconstriction index, collagen fiber content in lung parenchyma
(but not airways), eosinophil infiltration, and levels of interleukin (IL)-4, IL
13, transforming growth factor (TGF)-beta, and vascular endothelial growth factor
(VEGF) in lung homogenates compared to AD-MSCs and LUNG-MSCs. Only BM-MSCs
increased IL-10 and interferon (IFN)-gamma in lung tissue. In parallel in vitro
experiments, BM-MSCs increased M2 macrophage polarization, whereas AD-MSCs and
LUNG-MSCs had higher baseline levels of IL-4, insulin-like growth factor (IGF),
and VEGF secretion. Exposure of MSCs to serum specimens obtained from asthmatic
mice promoted reductions in secretion of these mediators, particularly in BM
MSCs. Intratracheally administered BM-MSCs, AD-MSCs, and LUNG-MSCs were
differentially effective at reducing airway inflammation and remodeling and
improving lung function in the current model of allergic asthma. In conclusion,
intratracheal administration of MSCs from BM, AD, and LUNG were differentially
effective at reducing airway inflammation and remodeling and improving lung
function comparably reduced inflammation and fibrogenesis in this asthma model.
However, altered lung mechanics and lung remodeling responded better to BM-MSCs
than to AD-MSCs or LUNG-MSCs. Moreover, each type of MSC was differentially
affected in a surrogate in vitro model of the in vivo lung environment. Stem
Cells Translational Medicine 2017;6:1557-1567.
PMID- 28425577
TI - Postoperative hemorrhage and hospital revisit after transoral robotic surgery.
AB - OBJECTIVES/HYPOTHESIS: To investigate the incidence and complications related to
postoperative hemorrhage (POH) after transoral robotic surgery (TORS). STUDY
DESIGN: Retrospective review of the State Inpatient Database (SID), the State
Ambulatory Surgery Database (SASD), and the State Emergency Department Database
(SEDD) from the Healthcare Cost and Utilization Project. METHODS: Patients were
identified from the SID, SASD, and SEDD for the states of Florida, New York, and
California from 2005 to 2013 who had an International Classification of Diseases,
Ninth Edition code for a surgical procedure on the upper aerodigestive tract
associated with a code for robotic-assisted surgery. Univariate logistic
regression was used to explore factors associated with POH. RESULTS: Five hundred
nine patients underwent TORS. Indications for surgery included neoplastic disease
in 376 (74%) and sleep apnea in 74 (15%). Forty-one (8%) had an episode of POH at
a median of 9 days postoperatively (range = 0-21 days). Twenty-four (5%) required
an intervention related to their POH. Sixteen (3%) required return to the
operating room for control of hemorrhage; 11 (2%) had a severe complication that
required embolization or tracheostomy. Charlson Comorbidity Score of >=3 (odds
ratio [OR] = 3.02, 95% confidence interval [CI] = 1.45-6.30) and a tonsillar
neoplasm (OR = 1.96, 95% CI = 1.03-3.74) were significantly associated with POH.
CONCLUSIONS: The incidence of POH after TORS was low, and few of these patients
had a severe complication related to this event. Medical comorbidity and
tonsillar subsite may be independent risk factors for POH. These data provide a
benchmark for informed decision making in TORS and a basis for further study.
LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2287-2292, 2017.
PMID- 28425578
TI - Survival comparisons of intensive vs. conventional hemodialysis: Pitfalls and
lessons.
AB - The optimal dose of hemodialysis (HD) has not yet been established. As a means of
better approximating the physiology of native kidney function, there has been a
growing interest in intensive HD (an increase in dialysis frequency and/or
duration). Although many studies have demonstrated a survival benefit with
intensive dialysis, results have been conflicting. This controversy stems from
the challenges of randomizing patients to conventional vs. intensive HD
modalities and, therefore, the reliance on observational comparisons that have
been limited by varying definitions for intensive dialysis, differences in
dialysis location and prescription, unavoidable treatment selection bias, and a
potential lack of generalizability. This review will discuss the pitfalls and
complexities surrounding survival comparisons with intensive HD, and identify
important directions for future study.
PMID- 28425579
TI - Myringoplasty Outcomes From the Swedish National Quality Registry.
AB - OBJECTIVES/HYPOTHESIS: Data from patients registered for myringoplasty during
2002 to 2012 in the Swedish National Quality Registry for Myringoplasty. STUDY
DESIGN: Both conventional myringoplasty and fat-graft techniques were used aimed
at healing the tympanic membrane in noninfected ears. METHODS: Analysis was
performed on data in a national database collected from 32 ear, nose, and throat
clinics. Surgical procedures and outcomes, and patient satisfaction from a
questionnaire were studied. RESULTS: The database was comprised of 3,775 surgical
procedures, with follow-up available for analysis. One-third were children under
the age of 15 years. The most common indication for surgery was infection
prophylaxis. The overall healing rate of the tympanic membrane after surgery was
88.5%, with a high mean patient satisfaction. Complications registered were
postoperative infection, tinnitus, or taste disturbance that occurred in 5.8% of
patients. CONCLUSIONS: Swedish results for a large number of patients who
completed myringoplasty are presented. The success rate in this study is
comparable to other studies, and good patient-reported outcome measures of
myringoplasty are presented. Databases for surgical procedures and clinical
audits are systematic processes for continuous learning in healthcare. This study
shows that clinical databases can be utilized to analyze national results of
surgical procedures. LEVEL OF EVIDENCE: 2b Laryngoscope, 127:2389-2395, 2017.
PMID- 28425580
TI - The patient safety climate in healthcare organizations (PSCHO) survey: Short-form
development.
AB - RATIONALE, AIMS, AND OBJECTIVES: Measures of safety climate are increasingly used
to guide safety improvement initiatives. However, cost and respondent burden may
limit the use of safety climate surveys. The purpose of this study was to develop
a 15- to 20-item safety climate survey based on the Patient Safety Climate in
Healthcare Organizations survey, a well-validated 38-item measure of safety
climate. METHODS: The Patient Safety Climate in Healthcare Organizations was
administered to all senior managers, all physicians, and a 10% random sample of
all other hospital personnel in 69 private sector hospitals and 30 Veterans
Health Administration hospitals. Both samples were randomly divided into a
derivation sample to identify a short-form subset and a confirmation sample to
assess the psychometric properties of the proposed short form. RESULTS: The short
form consists of 15 items represented 3 overarching domains in the long-form
scale-organization, work unit, and interpersonal. CONCLUSION: The proposed short
form efficiently captures 3 important sources of variance in safety climate:
organizational, work-unit, and interpersonal. The short-form development process
was a practical method that can be applied to other safety climate surveys. This
safety climate short form may increase response rates in studies that involve
busy clinicians or repeated measures.
PMID- 28425581
TI - Clinical, Biochemical, and Genetic Features of 41 Han Chinese Families With
Primary Hypertrophic Osteoarthropathy, and Their Therapeutic Response to
Etoricoxib: Results From a Six-Month Prospective Clinical Intervention.
AB - Primary hypertrophic osteoarthropathy (PHO) is a rare inherited disease caused by
genetic defects in the prostaglandin metabolism pathway; disturbed prostaglandin
E2 (PGE2 ) catabolism resulting in increased PGE2 level is suggested in the
pathogenesis. Forty-three Han Chinese patients with PHO were studied and 41 of
them were treated. Mutations in the HPGD gene, causing hypertrophic
osteoarthropathy, primary, autosomal recessive 1 (PHOAR1; OMIM 259100), were
identified in seven patients, and mutations in the SLCO2A1 gene, causing
hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2; OMIM
614441), were identified in 36 patients. Clinical phenotypes of PHO varied,
ranging from mild isolated finger clubbing to severe pachydermia and disabling
joint swelling, even within families. Circulating PGE2 metabolism features of
PHOAR2 were different from those of PHOAR1. Different frequency and severity of
pachydermia between the subgroups were also indicated. A percentage of PHOAR2
patients suffered from gastrointestinal hemorrhage, but this symptom was not
observed in the PHOAR1 subgroup. Clinical evidence highlighted the essential role
of sex hormones in prostaglandin transporter regulation with respect to PHOAR2
onset, although no significant associations of urinary PGE2 or PGE-M with sex
hormones were identified. Treatment with etoricoxib, a selective cyclooxygenase-2
inhibitor, was proved to be beneficial and safe. We detected its notable efficacy
in decreasing urinary PGE2 levels in the majority of the enrolled patients during
6 months of intervention; clinical phenotypes assessed, including pachydermia,
finger clubbing, and joint swelling, were improved. We found no visible evidence
of a positive effect of etoricoxib on periostosis; however, significant links
between urinary PGE2 and serum bone turnover markers indicated a potential role
of decreased PGE2 in periostosis management. This is the largest reported cohort
of subjects genetically diagnosed with PHO. For the first time, we systematically
investigated the biochemical and clinical differences between PHOAR1 and PHOAR2,
and prospectively showed the positive efficacy and safety of etoricoxib for PHO
patients. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28425582
TI - Personality, immune response and reproductive success: an appraisal of the pace
of-life syndrome hypothesis.
AB - The pace-of-life syndrome (POLS) hypothesis is an extended concept of the life
history theory that includes behavioural traits. The studies challenging the POLS
hypothesis often focus on the relationships between a single personality trait
and a physiological and/or life-history trait. While pathogens represent a major
selective pressure, few studies have been interested in testing relationships
between behavioural syndrome, and several fitness components including immunity.
The aim of this study was to address this question in the mealworm beetle,
Tenebrio molitor, a model species in immunity studies. The personality score was
estimated from a multidimensional syndrome based of four repeatable behavioural
traits. In a first experiment, we investigated its relationship with two measures
of fitness (reproduction and survival) and three components of the innate
immunity (haemocyte concentration, and levels of activity of the phenoloxidase
including the total proenzyme and the naturally activated one) to challenge the
POLS hypothesis in T. molitor. Overall, we found a relationship between
behavioural syndrome and reproductive success in this species, thus supporting
the POLS hypothesis. We also showed a sex-specific relationship between
behavioural syndrome and basal immune parameters. In a second experiment, we
tested whether this observed relationship with innate immunity could be confirmed
in term of differential survival after challenging by entomopathogenic bacteria,
Bacillus thuringiensis. In this case, no significant relationship was evidenced.
We recommend that future researchers on the POLS should control for differences
in evolutionary trajectory between sexes and to pay attention to the choice of
the proxy used, especially when looking at immune traits.
PMID- 28425583
TI - Sleep apnea syndrome, inflammation and oxidative stress in hemodialysis patients.
AB - INTRODUCTION: Sleep apnea syndrome (SAS) is an established cardiovascular risk
factor in the general population related to inflammation and oxidative stress and
is very common among hemodialysis patients. Cardiovascular disease and its
complications is the main cause of death among hemodialysis patients. The aim of
the present study was to investigate the role of SAS in the promotion of
inflammation and oxidative stress and thus in the augmentation of cardiovascular
risk in hemodialysis patients. METHODS: Thirty-seven hemodialysis patients
underwent an overnight full polysomnography study. The following morning blood
samples were obtained and TNF-alpha (tumor necrosis factor-alpha), IL-6
(interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density
lipoprotein) were measured. FINDINGS: We investigated the correlation of
patients' markers of inflammation and oxidative stress with their sleep
parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory
disturbance index; DI, desaturation index, mean and minimum SpO2 and percentage
of sleep time with SpO2 < 90%). TNF-alpha correlated positively with BMI (r =
0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated
positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r =
0.336, P = 0.042) and percentage of sleep time with SpO2 < 90% (r = 0.415, P =
0.012) and negatively with mean SpO2 (r = -0.364, P = 0.027). Myeloperoxidase
correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02)
and percentage of sleep time with SpO2 < 90% (r = 0.388, P = 0.019). Finally,
oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P =
0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO2 <90% (r =
0.389, P = 0.019). CONCLUSIONS: These results indicate that, in hemodialysis
patients, the severity of SAS and nocturnal hypoxia correlated positively with
markers of inflammation and oxidative stress.
PMID- 28425584
TI - Changes in cIAP2, survivin and BimEL expression characterize the switch from
autophagy to apoptosis in prolonged starvation.
AB - BACKGROUND: Autophagy is a catabolic process involving the engulfment of
cytoplasmic content within autophagosomes followed by their delivery to
lysosomes. This process is a survival mechanism, enabling cells to cope with
nutrient deprivation by degradation and recycling of macromolecules. Yet during
continued stress such as prolonged starvation, a switch from autophagy to
apoptosis is often detected. OBJECTIVE: In this work, we characterized the
temporal dynamics of the transition from autophagy towards apoptosis with the aim
of elucidating the molecular mechanism regulating the switch from survival
autophagy to apoptotic cell death. RESULTS AND CONCLUSIONS: We defined an inverse
relationship between apoptosis and autophagy spanning a period of 72 h,
manifested by the sequential reduction in LC3 lipidation and the activation of
caspase-3. The transition to apoptosis correlated with a selective decline in the
mRNA and protein levels of two anti-apoptotic IAP family proteins, survivin and
cIAP2 and a selective increase in the BH3-only protein, BimEL. This 'molecular
signature' was common to several cell lines undergoing the switch from autophagy
to apoptosis during prolonged starvation. Mechanistically, the increased BimEL
protein levels resulted from its reduced binding to its specific E3 ligase,
betaTrCP, leading to protein stabilization. Consistent with this, BimEL showed
decreased phosphorylation at critical sites previously reported to be essential
for binding to the E3 ligase. The decrease in the anti-apoptotic IAPs and the
increase in the pro-apoptotic BimEL may thus constitute a molecular switch from
autophagy to apoptosis during prolonged starvation.
PMID- 28425585
TI - Eosinophilic esophagitis: unclear roles of IgE and eosinophils.
AB - Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the
oesophagus. Recognized as a distinct entity only two decades ago, the emergence
of the disease along with the availability of new technologies has rapidly opened
new research avenues and outlined the main features of the pathogenesis of EoE.
Yet, each advance in our understanding of the disease has raised new questions
about the previous consensus. Currently, new subsets of the disease challenge our
diagnostic criteria. For instance, it was believed that EoE did not respond to
proton pump inhibitor (PPI) therapy; however, it has now been shown that a
substantial proportion of EoE patients indeed respond to PPIs. In addition, a new
subset of patients not even presenting eosinophil infiltrates in the oesophagus
has also been described. Moreover, approaches for better understanding the
heritability of the disease bring into question the dogma of predominant genetic
involvement. Furthermore, the specificity and sensitivity of allergy testing for
targeted food avoidance is highly controversial, and the production of specific
antibodies in EoE now includes IgG4 in addition to IgE. In conclusion, EoE is
perceived as 'a moving target' and the aim of this review was to summarize the
current understanding of EoE pathogenesis.
PMID- 28425586
TI - Introduction to Nobel Conference: 'The Cell Cycle and Cell Death in Disease'.
PMID- 28425587
TI - Hybrid finite difference/finite element immersed boundary method.
AB - The immersed boundary method is an approach to fluid-structure interaction that
uses a Lagrangian description of the structural deformations, stresses, and
forces along with an Eulerian description of the momentum, viscosity, and
incompressibility of the fluid-structure system. The original immersed boundary
methods described immersed elastic structures using systems of flexible fibers,
and even now, most immersed boundary methods still require Lagrangian meshes that
are finer than the Eulerian grid. This work introduces a coupling scheme for the
immersed boundary method to link the Lagrangian and Eulerian variables that
facilitates independent spatial discretizations for the structure and background
grid. This approach uses a finite element discretization of the structure while
retaining a finite difference scheme for the Eulerian variables. We apply this
method to benchmark problems involving elastic, rigid, and actively contracting
structures, including an idealized model of the left ventricle of the heart. Our
tests include cases in which, for a fixed Eulerian grid spacing, coarser
Lagrangian structural meshes yield discretization errors that are as much as
several orders of magnitude smaller than errors obtained using finer structural
meshes. The Lagrangian-Eulerian coupling approach developed in this work enables
the effective use of these coarse structural meshes with the immersed boundary
method. This work also contrasts two different weak forms of the equations, one
of which is demonstrated to be more effective for the coarse structural
discretizations facilitated by our coupling approach.
PMID- 28425588
TI - Drug resistance reversal by combretastatin-A4 phosphate loaded with doxorubicin
in polymersomes independent of angiogenesis effect.
AB - OBJECTIVES: This study aimed to evaluate that the polymersomes (Ps-DOX-CA4P) dual
loaded with combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) overcame
drug resistance and sensitized tumour cells to chemotherapeutic drugs. METHODS:
Ps-DOX-CA4P were prepared by solvent evaporation method using mPEG-b-PLA as
carriers. The potential capability of CA4P to reverse DOX resistance was verified
by cytotoxicity test, apoptosis assay and cellular uptake of DOX. The comparison
between free drugs and drug-loaded polymersomes was also made on a single-layer
cell model and multicellular tumour spheroids to display the superiority of the
drug vehicles. Furthermore, we put the emphasis on the investigation into
underlying mechanisms for CA4P overcoming DOX resistance. KEY FINDINGS: Results
showed Ps-DOX-CA4P achieved increased uptake of DOX, enhanced cytotoxicity and
apoptotic rate in MCF-7/ADR cells as well as MCF-7/ADR tumour spheroids. The
potential molecular mechanisms may be related to inhibiting P-glycoprotein
function by downregulating protein kinase Calpha, stimulating ATPase activity,
depleting ATP and increasing intracellular reactive oxygen species levels.
CONCLUSIONS: The findings validated the sensitization property of CA4P on DOX
independent of its well-known angiogenesis effect, which would provide a novel
and promising strategy for drug-resistant cancer therapy.
PMID- 28425589
TI - National Rates of Uterine Rupture are not Associated with Rates of Previous
Caesarean Delivery: Results from the Nordic Obstetric Surveillance Study.
AB - BACKGROUND: Previous caesarean delivery and intended mode of delivery after
caesarean are well-known individual risk factors for uterine rupture. We examined
if different national rates of uterine rupture are associated with differences in
national rates of previous caesarean delivery and intended mode of delivery after
a previous caesarean delivery. METHODS: This study is an ecological study based
on data from a retrospective cohort in the Nordic countries. Data on uterine
rupture were collected prospectively in each country as part of the Nordic
obstetric surveillance study and included 91% of all Nordic deliveries.
Information on the comparison population was retrieved from the national medical
birth registers. Incidence rate ratios by previous caesarean delivery and
intended mode of delivery after caesarean were modelled using Poisson regression.
RESULTS: The incidence of uterine rupture was 7.8/10 000 in Finland and 4.6/10
000 in Denmark. Rates of caesarean (21.3%) and previous caesarean deliveries
(11.5%) were highest in Denmark, while the rate of intended vaginal delivery
after caesarean was highest in Finland (72%). National rates of uterine rupture
were not associated with the population rates of previous caesarean but increased
by 35% per 1% increase in the population rate of intended vaginal delivery and in
the subpopulation of women with previous caesarean delivery by 4% per 1% increase
in the rate of intended vaginal delivery. CONCLUSION: National rates of uterine
rupture were not associated with national rates of previous caesarean, but
increased with rates of intended vaginal delivery after caesarean.
PMID- 28425590
TI - Role of upper gastrointestinal contrast studies for suspected malrotation in
neonatal population.
AB - AIM: Upper gastrointestinal (UGI) contrast study is the preferred radiological
investigation to diagnose malrotation of intestine. We aimed to review the role
of UGI contrast in neonates (term and preterm) who were clinically suspected to
have malrotation. METHODS: The study included a retrospective review of medical
charts and radiology reports. RESULTS: A total of 164 newborn infants underwent
UGI contrast study to rule out malrotation during the study period (2006-2015).
Median gestational age at the time of presentation was 38 weeks (interquartile
range: 35.5-39.6 weeks). Median age for clinical presentation was day 2 of life
(interquartile range: 2-5 days). Out of the 164 contrast studies, 112 were
normal, whereas 52 were reported to have malrotation. Of those 52 infants, 47
were confirmed to have malrotation on surgery (positive predictive value: 90). Of
the 112 infants with normal UGI contrasts, nine infants underwent laparotomy for
ongoing clinical symptoms out of which four infants were diagnosed to have
malrotation on laparotomy. There were 22 infants born at gestational age <32
weeks, who underwent UGI contrast studies to rule out malrotation. Their clinical
symptoms were similar to necrotising enterocolitis. Of 22 preterm contrast
studies, six were reported to have malrotation; of these, five had surgically
confirmed malrotation. No complications related to the contrast study were noted
in both term and preterm infants. CONCLUSION: Current study reaffirms the role of
UGI contrast study as the investigation of choice for diagnosis of malrotation,
in both term and preterm infants. UGI contrast is safe and well tolerated even in
preterm infants.
PMID- 28425591
TI - REFLECTIVE FUNCTIONING AND PERSONALITY ORGANIZATION: ASSOCIATIONS WITH NEGATIVE
MATERNAL BEHAVIORS.
AB - The aim of this study was to examine whether mothers who manifest insensitive and
disconnected behaviors in interaction with their infants differ in terms of
maternal reflective functioning (RF), personality organization, and histories of
abuse. A total of 86 mother-infant dyads, 28 of them with histories of abuse,
participated in the study. RF was assessed with the Adult Attachment Interview
(C. George, N. Kaplan, & M. Main, 1985), and personality organization was
assessed with the self-report Inventory of Personality Organization (M.F.
Lenzenweger, J.F. Clarkin, O.F. Kernberg, & P.A. Foelsh, 2001; L. Normandin et
al., 2002), before the birth of the baby. Maternal behaviors were assessed using
the Disconnected and Extremely Insensitive Parenting measure when the infants
were 15 to 18 months old. The results of multivariate analyses of covariance
indicate that both RF and personality organization were associated with
disconnected and extremely insensitive maternal behaviors. Mothers classified as
presenting intrusive/aggressive behaviors had significantly lower RF as well as
significantly more difficulties in personality organization, including reality
testing, identity, and defense mechanisms. Withdrawn and disconnected maternal
behaviors were associated with the combination of difficulties in mentalization
and personality organization rather than difficulties in one specific area. In
sum, the study provides new evidence regarding the importance of a mentalizing
stance about early attachment relationships for the modulation of maternal
behaviors, especially intrusive/aggressive behaviors.
PMID- 28425592
TI - Mesoporous titanium oxide with high-specific surface area as a coating for in
tube solid-phase microextraction combined with high-performance liquid
chromatography for the analysis of polycyclic aromatic hydrocarbons.
AB - Stainless-steel wires coated with mesoporous titanium oxide were placed into a
polyether ether ketone tube for in-tube solid-phase microextraction, and the
coating sorbent was characterized by X-ray diffraction and scanning electron
microscopy. It was combined with high-performance liquid chromatography to build
an online system. Using eight polycyclic aromatic hydrocarbons as the analytes,
some conditions including sample flow rate, sample volume, organic solvent
content, and desorption time were investigated. Under optimum conditions, an
online analysis method was established and provided good linearity (0.03-30
MUg/L), low detection limits (0.01-0.10 MUg/L), and high enrichment factors (77.6
678). The method was applied to determine target analytes in river water and
water sample of coal ash, and the recoveries are in the range of 80.6-106.6 and
80.9-103.5%, respectively. Compared with estrogens and plasticizers, extraction
coating shows better extraction efficiency for polycyclic aromatic hydrocarbons.
PMID- 28425593
TI - Medium-sized nevus spilus of the neck treated with pulsed dye laser.
AB - Patients with large benign melanocytic lesions located on the neck represent a
therapeutic challenge since the neck is a high-risk area for hypertrophic
scarring and/or retraction. When treating a benign, extensive and visible
melanocytic lesion, the choice of therapy mainly depends on the likelihood of
improved cosmesis. We report a case of a 33-year-old woman with a medium-sized
Nevus Spilus located on the neck, successfully treated with four sessions of
pulsed dye laser. We achieved an excellent clinical and cosmetic result in such a
challenging area. No scarring, distortion or significant dyscromia were observed
after 24 months.
PMID- 28425594
TI - Trilobed pedicled superior gluteal artery perforator flap for lumbosacral defect
coverage.
AB - BACKGROUND: There are many available options for the coverage of lumbosacral area
defects. Surgeons usually use the superior gluteal artery perforator flap (SGAP)
by rotational fashion, which risks complications, such as wound dehiscence or
skin necrosis at the Y-point on the donor site due to the tension. In this
report, the authors present the experience of using trilobed pedicled SGAP flaps
in coverage of the lumbosacral area defects. METHODS: From 2011 to 2015, 16
trilobed pedicled SGAP flaps were performed for the coverage of sacral defects in
our facility. The average defect sizes were 9.3 cm * 7.4 cm (ranging from 5 cm *
4 cm to 13 cm * 13 cm ). Trilobed flap were designed to include a reliable
perforator vessel and rotated 90 degrees to the defect. All flaps included only
one perforator vessel. RESULTS: The average of flap sizes were 15.9 cm * 9.2 cm
(ranging from 10 cm * 20 to 5 cm * 15 cm). Two cases of minimal distal margin
necrosis (<1 cm) were reported in the flap tip area. The unviable distal area was
completely healed after the excision and primary closure. All flaps survived
completely. Patients were followed for an average of 14.8 months postoperatively
(ranging 6-20 months). There was no recurrence of the pressure sore during the
follow-up period. CONCLUSION: Trilobed pedicled SGAP flap successfully
reconstructed various sized defects and reduced the distortion and tension of the
wound, minimizing wound complications. This flap could reduce the hospital stay
and the recurrence of the pressure sore.
PMID- 28425595
TI - Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry
based study assessing risk of disability pension.
AB - BACKGROUND: Atopic dermatitis and hand eczema often impair the ability of people
to work. Only a few studies have investigated whether individuals with loss-of
function filaggrin gene (FLG) mutations, who often have severe and early onset of
dermatitis, experience occupational consequences. OBJECTIVE: To investigate the
personal consequences of having atopic dermatitis and/or hand eczema and FLG
mutations. METHOD: Adult Danes from the general population (n = 3247) and
patients with atopic dermatitis and/or hand eczema (n = 496) were genotyped for
common FLG mutations, and completed a questionnaire about skin symptoms and hand
eczema. Socioeconomic variables, including disability pension, and information on
work in risk occupations were retrieved from national registries. The reasons for
granting disability pension were unknown. RESULTS: Disability pension was
associated with hand eczema in the general population, especially among
individuals with a history of atopic dermatitis. Moreover, self-reported hand
eczema and atopic dermatitis were associated with particularly high risk of
disability pension among FLG mutation carriers [odds ratio (OR) 4.02 and 95%
confidence interval (CI): 1.15-14.11; and OR 6.01 and 95%CI: 2.37-15.34,
respectively]. Furthermore, 60% of the FLG mutation carriers with atopic
dermatitis who developed hand eczema had experienced symptoms before adulthood.
CONCLUSION: In the general population, self-reported hand eczema and atopic
dermatitis, particularly in individuals with a genetically impaired skin barrier,
were associated with disability pension, suggesting that FLG mutations carriers
with a history of atopic dermatitis and hand eczema could benefit from early
attention with respect to choice of occupation.
PMID- 28425597
TI - Too many instruments for measuring Quality of Life in Atopic Dermatitis.
PMID- 28425596
TI - Histamine intolerance in chronic urticaria.
PMID- 28425598
TI - Quality of life - an essential parameter for dermatology.
PMID- 28425599
TI - The starch-binding domain family CBM41-An in silico analysis of evolutionary
relationships.
AB - Within the CAZy database, there are 81 carbohydrate-binding module (CBM)
families. A CBM represents a non-catalytic domain in a modular arrangement of
glycoside hydrolases (GHs). The present in silico study has been focused on
starch-binding domains from the family CBM41 that are usually part of
pullulanases from the alpha-amylase family GH13. Currently there are more than
1,600 sequences classified in the family CBM41, almost exclusively from Bacteria,
and so a study was undertaken in an effort to divide the members into relevant
groups (subfamilies) and also to contribute to the evolutionary picture of family
CBM41. The CBM41 members adopt a beta-sandwich fold (~100 residues) with one
carbohydrate-binding site formed by the side-chains of three aromatic residues
that interact with carbohydrate. The family CBM41 can be divided into two basic
subdivisions, distinguished from each other by a characteristic sequence pattern
or motif of the three essential aromatics as follows: (i) "W-W-~10aa-W" (the so
called Streptococcus/Klebsiella-type); and (ii) "W-W-~30aa-W" (Thermotoga-type).
Based on our bioinformatics analysis it is clear that the first and second
positions of the motif can be occupied by aromatic residues (Phe, Tyr, His) other
than tryptophan, resulting in the existence of six different carbohydrate-binding
CBM41 groups, that reflect mostly differences in taxonomy, but which should
retain the ability to bind an alpha-glucan. In addition, three more groups have
been proposed that, although lacking the crucial aromatic motif, could possibly
employ other residues from remaining parts of their sequence for binding
carbohydrate. Proteins 2017; 85:1480-1492. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425600
TI - CAR-T cell manufacturing: time to put it in gear.
PMID- 28425601
TI - The confusion continues: evolving nature of massive transfusion protocol practice
may reflect lack of evidence to support a single solution that fits all.
PMID- 28425602
TI - Implementation of pathogen inactivation technology: how to make the best
decisions?
PMID- 28425603
TI - Encouraging single-unit transfusions: a superior patient blood management
strategy?
PMID- 28425604
TI - Assuring hospital supply of fresh red blood cells for critically ill patients.
PMID- 28425606
TI - A novel B allele with c.28 + 5885C>T substitution in the erythroid cell-specific
regulatory element identified in an individual with phenotype B3.
PMID- 28425607
TI - Reducing the risk of septic transfusion reactions from platelets.
PMID- 28425608
TI - Response to Assuring hospital supply of fresh red blood cells for critically ill
patients.
PMID- 28425609
TI - Clostridium perfringens sepsis masquerading as a hemolytic transfusion reaction.
PMID- 28425610
TI - Bacterial screening of platelet components by National Health Service Blood and
Transplant, an effective risk reduction measure.
AB - BACKGROUND: Bacterial contamination of blood components remains a major cause of
sepsis in transfusion medicine. Between 2006 and 2010 in the 5 years before the
introduction of bacterial screening of platelet (PLT) components by National
Health Service Blood and Transplant (NHSBT), seven cases of PLT component
associated transmission of bacterial infection were recorded for 10 patients,
three of which were fatal. STUDY DESIGN AND METHODS: Sampling of individual PLT
components was undertaken at 36 to 48 hours after donation and tested in the
BacT/ALERT system with 8 mL inoculated into each of aerobic and anaerobic culture
bottles. Bottles were incubated until the end of the 7-day shelf life and initial
reactive bottles were examined for contamination. Bacterial screened time-expired
PLTs were tested as in the screen method. RESULTS: From February 2011 to
September 2015, a total of 1,239,029 PLT components were screened. Initial
reactive, confirmed-positive, and false-positive rates were 0.37, 0.03, and
0.19%, respectively. False-negative cultures, all with Staphylococcus aureus,
occurred on four occasions; three were visually detected before transfusion and
one confirmed transmission resulted in patient morbidity. The NHSBT screening
protocol effectively reduced the number of clinically adverse transfusion
transmissions by 90% in this reporting period, compared to a similar time period
before implementation. Delayed testing of 4515 time-expired PLT units after
screening revealed no positives. CONCLUSION: The implementation of bacterial
screening of PLT components with the NHSBT BacT/ALERT protocol was an effective
risk reduction measure and increased the safety of the blood supply.
PMID- 28425611
TI - A simple assessment tool for evaluation of cadaveric temporal bone dissection.
AB - EDUCATIONAL OBJECTIVE: Objective metrics in skilled-based educational courses
allow trainees and instructors to assess performance and monitor progress. The
objective is to validate a concise, easy-to-use instrument for assessment of
resident skill during a timed cadaveric temporal-bone (CTB) dissection. STUDY
DESIGN: Retrospective analysis. METHODS: An instrument was developed to assess
resident performance on a yearly timed microdissection of CTB. Five
neurotologists participated in the assessment. Each reviewer's score was compared
to the score given by the senior neurotologist each year for every resident.
Spearman's correlation analysis was then used to assess the reproducibility of
the instrument in assessing resident performance. The ability of the instrument
to distinguish among experienced and novice trainees and to demonstrate
improvement with experience were also assessed. RESULTS: The instrument was
created and used for 6 years. Thirty residents were assessed. Correlation of
scores between the senior neurotologist and the other neurotologist together was
very high (r = 0.883, P < 0.001). Three specific tasks distinguished novice from
senior dissectors: posterior canal, opening the membranous labyrinth, and
disruption of the ossicular chain. CONCLUSION: A new instrument for assessment of
resident skill on CTB dissection is presented. The instrument is easy to use, and
scores derived from it are consistent across reviewers. The new instrument
distinguishes experienced trainees from novice trainees, is sensitive to
individual experience, and has proved useful in providing trainees with objective
performance measures. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:451-455, 2018.
PMID- 28425612
TI - Oral Health Programmes in Indigenous Communities Worldwide-Lessons learned from
the field: A qualitative systematic review.
AB - OBJECTIVES: This systematic review examines the evidence on the effectiveness of
programmes that aim to improve the oral health of Indigenous populations
worldwide, as well as presents a qualitative analysis to explore the design and
implementation of these initiatives. METHODS: MEDLINE and EMBASE were searched.
Studies were included if they described an oral health programme for an
Indigenous population in any country worldwide. A thematic synthesis of the
qualitative findings was undertaken for each study's results and discussion
sections. RESULTS: Nineteen studies were included. Sixteen studies reported
positive results, twelve of which reported statistically significant findings.
Three themes regarding design and implementation emerged from the qualitative
analysis: (i) elements of successful programmes, (ii) challenges and barriers to
successful interventions and (iii) suggestions for improvements. CONCLUSIONS:
Successful programmes considered cultural appropriateness in their design
including extensive community engagement before, during and after implementation
to enhance ownership of, and thus participation in the programme. Collaborative
approaches were seen as an advantage, not only with Indigenous communities, but
also with local health providers and organizations, with particular emphasis on
incorporation into existing services. Challenges included low community
participation, unstable funding and staffing issues. In addition, future
programmes should also incorporate advocacy and community development, focus on
changes to public policy, utilize evidence-based interventions that include
traditional models of health, attempt to secure a stable funding base, target
strategies to ensure staff retention and develop interventions that target the
multilevel causes of general and oral health. This review provides an evidence
base that can aid in the successful design, implementation and sustainability of
oral health programmes for Indigenous people in the future.
PMID- 28425613
TI - UVA 1 laser in the treatment of patients with vitiligo.
PMID- 28425614
TI - Stigmatization and self-determination of preregistration nurses: A path analysis.
AB - The concept of stigma and the stigmatizing behaviours of health-care
professionals can have a profound influence on people with mental illness. A key
construct that has been identified as influencing our behaviours is self
determination. As such, in the present study, we attempted to examine the
connection and influence of motivational measures on the stigmatization of
preregistration nurses. Data were collected once using three surveys that
measured the motivational responses and stigmatizing behaviours of
preregistration nurses after an approved mental health clinical placement. Using
a path analysis, the results indicated that psychological needs significantly
influenced preregistration nurses' self-determination towards work. In addition,
self-determination was a significant influence on the stigmatization behaviours
of preregistration nurses. The results of the present study provide initial
empirical evidence that supports the importance of professional self
determination and the potential connection of quality care, as illustrated with
the low stigmatizing behaviours of preregistration nurses who are more self
determined towards their work/career. Because of the significant results of the
present study, it is recommended that future research is needed that uses self
determination theory as a lens to understand the application and importance
within the field of nurse education.
PMID- 28425615
TI - The natural history of subjective tinnitus in adults: A systematic review and
meta-analysis of no-intervention periods in controlled trials.
AB - OBJECTIVES: Tinnitus is a prevalent condition, but little has been published
regarding the natural history of the condition. One technique for evaluating the
long-term progression of the disease is to examine what happens to participants
in the no-intervention control arm of a clinical trial. The aim of this study was
to examine no-intervention or waiting-list data reported in trials, in which
participants on the active arm received any form of tinnitus intervention. DATA
SOURCES: CINAHL, PsychINFO, EMBASE, ASSIA, PubMed, Web of Science, Science
Direct, EBSCO Host, and Cochrane. METHODS: Inclusion criteria followed the PICOS
principles: Participants, adults with tinnitus; Intervention, none; Control, any
intervention for alleviating tinnitus; Outcomes, a measure assessing tinnitus
symptoms using a multi-item patient-reported tinnitus questionnaire. Secondary
outcome measures included multi-item patient-reported questionnaires of mood and
health-related quality of life and measures that quantified change in tinnitus
loudness; Study design, randomized controlled trials or observational studies
utilizing a no-intervention or waiting-list control group. Data were extracted
and standardized mean difference was calculated for each study to enable meta
analysis. RESULTS: The evidence strongly favored a statistically significant
decrease in the impact of tinnitus over time, though there was significant
heterogeneity and clinical significance cannot be interpreted. Outcome data
regarding secondary measures did not demonstrate any clinically significant
change. CONCLUSIONS: Participants allocated to the no-intervention or waiting
list control arm of clinical trials for a tinnitus intervention show a small but
significant improvement in self-reported measures of tinnitus with time; the
clinical significance of this finding is unknown. There is, however, considerable
variation across individuals. These findings support previous work and can
cautiously be used when counseling patients. Laryngoscope, 128:217-227, 2018.
PMID- 28425618
TI - Classifying Adults with Binge Eating Disorder Based on Severity Levels.
AB - The clinical utility of the severity criterion for binge eating disorder (BED),
introduced in the DSM-5 as a means of addressing heterogeneity and variability in
the severity of this disorder, was evaluated in 189 treatment-seeking adults with
(DSM-5) BED. Participants classified with mild, moderate, severe and extreme
severity of BED, based on their weekly frequency of binge eating episodes,
differed significantly from each other in body mass index (BMI), eating disorder
features, putative factors involved in the maintenance process of the disorder,
comorbid mood, anxiety and personality disorders, psychological distress, social
maladjustment and illness-specific functional impairment (medium-to-large effect
sizes). They were also statistically distinguishable in metabolic syndrome
prevalence, even after adjusting for BMI (large effect size), suggesting the
possibility of non-BMI-mediated mechanisms. The implications of the findings,
providing support for the utility of the binge frequency as a severity criterion
for BED, and directions for future research are outlined. Copyright (c) 2017 John
Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 28425617
TI - Some posterior branches of extralaryngeal recurrent laryngeal nerves have motor
fibers.
AB - OBJECTIVES/HYPOTHESIS: Anatomical variations of the recurrent laryngeal nerve
(RLN), such as extralaryngeal branching, are a well-known risk factor for RLN
injury during thyroid surgery. This study aimed to analyze the surgical anatomy
and to investigate the existence of posterior branch motor fibers of
extralaryngeal RLNs. STUDY DESIGN: Prospective consecutive observational study.
METHODS: This was a prospective cohort study of 366 patients between January 2014
and February 2016. Operative data included the type of operation, incidence of
nerve bifurcation, the distances among anatomical landmarks. The motor fibers
were evaluated using neurostimulation with laryngeal palpation. RESULTS: A total
of 667 RLNs at risk were analyzed in this study, and of these 103 (14.5%) nerves
were bifurcated or trifurcated before the laryngeal entry point (LEP). More
extralaryngeal branched RLNs were observed on the right side than on the left
(17.5% vs. 13.3%, P = .294). The mean distance of the LEP point of division was
longer on the left side (16.2 +/- 6.7 mm) than on the right (14.7 +/- 5.9 mm, P =
.132). All branched RLNs had a palpable laryngeal twitch when stimulating
anterior branches. When stimulating posterior branches, 28.2%(29/103) of branched
RLNs showed palpable laryngeal twitch. Overall incidence of posterior motor
branch in total RLNs was 4.3% (29/667). CONCLUSIONS: The motor fibers of the RLN
are all located in the anterior branch, whereas some posterior branches have
motor function. Identification of all of the branches of the RLN may be mandatory
to decrease the risk of postoperative nerve injury. LEVEL OF EVIDENCE: 4.
Laryngoscope, 127:2678-2685, 2017.
PMID- 28425616
TI - Statin use and risk of multiple myeloma: An analysis from the cancer research
network.
AB - Animal and human data suggest statins may be protective against developing
multiple myeloma; however, findings may be biased by the interrelationship with
lipid levels. We investigated the association between statin use and risk of
multiple myeloma in a large US population, with an emphasis on accounting for
this potential bias. We conducted a case-control study nested within 6 US
integrated healthcare systems participating in the National Cancer Institute
funded Cancer Research Network. Adults aged >=40 years who were diagnosed with
multiple myeloma from 1998-2008 were identified through cancer registries (N =
2,532). For each case, five controls were matched on age, sex, health plan, and
membership duration prior to diagnosis/index date. Statin prescriptions were
ascertained from electronic pharmacy records. To address potential biases related
to lipid levels and medication prescribing practices, multivariable marginal
structural models were used to model statin use (>=6 cumulative months) and risk
of multiple myeloma, with examination of multiple latency periods. Statin use 48
72 months prior to diagnosis/index date was associated with a suggestive 20-28%
reduced risk of developing multiple myeloma, compared to non-users. Recent
initiation of statins was not associated with myeloma risk (risk ratio range 0.90
0.99 with 0-36 months latency). Older patients had more consistent protective
associations across all latency periods (risk ratio range 0.67-0.87). Our results
suggest that the association between statin use and multiple myeloma risk may
vary by exposure window and age. Future research is warranted to investigate the
timing of statin use in relation to myeloma diagnosis.
PMID- 28425619
TI - Analysis of mutations in the SOS-1 gene in two Polish families with hereditary
gingival fibromatosis.
AB - OBJECTIVES: To establish whether two families from Malopolska and Mazovia
provinces in Poland are affected by hereditary gingival fibromatosis type 1,
caused by a single-cytosine insertion in exon 21 of the Son-of-Sevenless-1 gene.
MATERIAL AND METHODS: Six subjects with hereditary gingival fibromatosis and five
healthy subjects were enrolled in the study. Gingival biopsies were collected
during gingivectomy or tooth extraction and used for histopathological
evaluation. Total RNA and genomic DNA were purified from cultured gingival
fibroblasts followed by cDNA and genomic DNA sequencing and analysis. RESULTS:
Hereditary gingival fibromatosis was confirmed by periodontal examination, X-ray,
and laboratory tests. Histopathological evaluation showed hyperplastic
epithelium, numerous collagen bundles, and abundant-to-moderate fibroblasts in
subepithelial and connective tissue. Sequencing of exons 19-22 of the Son-of
Sevenless-1 gene did not reveal a single-cytosine insertion nor other mutations.
CONCLUSIONS: Patients from two Polish families under study had not been affected
by hereditary gingival fibromatosis type 1, caused by a single-cytosine insertion
in exon 21 of the Son-of-Sevenless-1 gene. Further studies of the remaining
regions of this gene as well as of other genes are needed to identify disease
related mutations in these patients. This will help to unravel the pathogenic
mechanism of gingival overgrowth.
PMID- 28425620
TI - Periarticular Bone Loss in Arthritis Is Induced by Autoantibodies Against
Citrullinated Vimentin.
AB - Periarticular bone loss is a long known but yet insufficiently understood
phenomenon in patients with rheumatoid arthritis. This study investigated whether
autoimmunity against citrullinated proteins is causally involved in triggering
periarticular bone loss. Periarticular bone loss was studied in the standard
antigen-induced arthritis (AIA) mouse model with methylated bovine serum albumin
(mBSA) as well as a modified model with mutated citrullinated vimentin (MCV)
alone or in combination with mBSA. Periarticular bone loss, subchondral
osteoclastogenesis, as well as local expression of cytokines, osteoclast genes,
and peptidyl-arginine deiminase (PAD) enzymes were assessed after arthritis
induction. Immune cell and osteoclast precursor infiltration were detected in the
periarticular bone marrow and local lymph nodes. In addition, periarticular bone
loss was assessed upon challenge of mice with purified anti-MCV antibody. Despite
inducing a milder form of arthritis than mBSA, MCV triggered significant
periarticular bone loss associated with an increased infiltration of osteoclast
precursors and mature osteoclasts in the periarticular bone marrow. MCV enhanced
the expression of the osteoclast inducers RANKL and M-CSF, the cytokines IL-8, IL
1, IL-6, and TNF-alpha, as well as PAD2 and PAD4 enzymes in the periarticular
bone marrow. Furthermore, also anti-MCV antibody challenge induced significant
periarticular bone loss and local osteoclastogenesis in the mice. Autoimmunity
against citrullinated vimentin triggers periarticular bone loss by osteoclast
activation in the bone marrow. These findings may explain why periarticular bone
loss is already found very early in the disease course of patients with
rheumatoid arthritis. (c) 2017 American Society for Bone and Mineral Research.
PMID- 28425621
TI - p53-competent cells and p53-deficient cells display different susceptibility to
oxygen functionalized graphene cytotoxicity and genotoxicity.
AB - Due to the distinctive physical, electrical, and chemical properties of graphene
nanomaterials, numerous efforts pursuing graphene-based biomedical and industrial
applications are underway. Oxidation of pristine graphene surfaces mitigates its
otherwise hydrophobic characteristic thereby improving its biocompatibility and
functionality. Yet, the potential widespread use of oxidized graphene derivatives
raises concern about adverse impacts on human health. The p53 tumor suppressor
protein maintains cellular and genetic stability after toxic exposures. Here, we
show that p53 functional status correlates with oxygen functionalized graphene (f
G) cytotoxicity and genotoxicity in vitro. The f-G exposed p53-competent cells,
but not p53-deficient cells, initiated G0 /G1 phase cell cycle arrest, suppressed
reactive oxygen species, and entered apoptosis. There was p53-dependent f-G
genotoxicity evident as increased structural chromosome damage, but not increased
gene mutation or chromatin loss. In conclusion, the cytotoxic and genotoxic
potential for f-G in exposed cells was dependent on the p53 functional status.
These findings have broad implications for the safe and effective implementation
of oxidized graphene derivatives into biomedical and industrial applications.
Published 2017. This article has been contributed to by US Government employees
and their work is in the public domain in the USA.
PMID- 28425623
TI - Volunteerism, and alignment, are needed for a major paradigm shift in approaches
to hypertension control: 2016 World Hypertension League Excellence Award in
Hypertension Prevention and Control and the Distinguished Service Award.
PMID- 28425622
TI - Targeted Disruption of NF1 in Osteocytes Increases FGF23 and Osteoid With
Osteomalacia-like Bone Phenotype.
AB - Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations,
exhibits multi-system abnormalities, including skeletal deformities in humans.
Osteocytes play critical roles in controlling bone modeling and remodeling.
However, the role of neurofibromin, the protein product of the NF1 gene, in
osteocytes is largely unknown. This study investigated the role of neurofibromin
in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout
(Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an
osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in
cKO mice compared with age-matched controls. In addition, calcium-phosphorus
metabolism was significantly altered (calcium reduced; phosphorus reduced;
parathyroid hormone [PTH] increased; 1,25(OH)2 D decreased). Bone
histomorphometry showed dramatically increased osteoid parameters, including
osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed
reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP
staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and
porous cortical bones in the cKO mice, in which osteocyte dendrites were
disorganized as assessed by electron microscopy. Interestingly, the cKO mice
exhibited spontaneous fractures in long bones, as found in NF1 patients.
Mechanical testing of femora revealed significantly reduced maximum force and
stiffness. Immunohistochemistry showed significantly increased FGF23 protein in
the cKO bones. Moreover, primary osteocytes from cKO femora showed about
eightfold increase in FGF23 mRNA levels compared with control cells. The
upregulation of FGF23 was specifically and significantly inhibited by PI3K
inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1
deficient osteocytes. Taken together, these results indicate that Nf1 deficiency
in osteocytes dramatically increases FGF23 production and causes a mineralization
defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus
metabolism. This study demonstrates critical roles of neurofibromin in osteocytes
for osteoid mineralization. (c) 2017 American Society for Bone and Mineral
Research.
PMID- 28425624
TI - A Statistical Approach to Fine Mapping for the Identification of Potential Causal
Variants Related to Bone Mineral Density.
AB - Although genomewide association studies (GWASs) have been able to successfully
identify dozens of genetic loci associated with bone mineral density (BMD) and
osteoporosis-related traits, very few of these loci have been confirmed to be
causal. This is because in a given genetic region there may exist many trait
associated SNPs that are highly correlated. Although this correlation is useful
for discovering novel associations, the high degree of linkage disequilibrium
that persists throughout the genome presents a major challenge to discern which
among these correlated variants has a direct effect on the trait. In this study
we apply a recently developed Bayesian fine-mapping method, PAINTOR, to determine
the SNPs that have the highest probability of causality for femoral neck (FNK)
BMD and lumbar spine (LS) BMD. The advantage of this method is that it allows for
the incorporation of information about GWAS summary statistics, linkage
disequilibrium, and functional annotations to calculate a posterior probability
of causality for SNPs across all loci of interest. We present a list of the top
10 candidate SNPs for each BMD trait to be followed up in future functional
validation experiments. The SNPs rs2566752 (WLS) and rs436792 (ZNF621 and CTNNB1)
are particularly noteworthy because they have more than 90% probability to be
causal for both FNK and LS BMD. Using this statistical fine-mapping approach we
expect to gain a better understanding of the genetic determinants contributing to
BMD at multiple skeletal sites. (c) 2017 American Society for Bone and Mineral
Research.
PMID- 28425625
TI - A missense mutation in damage-specific DNA binding protein 2 is a genetic risk
factor for limbal squamous cell carcinoma in horses.
AB - Squamous cell carcinoma (SCC) is the most common cancer of the equine eye,
frequently originating at the limbus, with the potential to invade the cornea,
cause visual impairment, and result in loss of the eye. Several breeds of horses
have a high occurrence of limbal SCC implicating a genetic basis for limbal SCC
predisposition. Pedigree analysis in the Haflinger breed supports a simple
recessive mode of inheritance and a genome-wide association study (N = 23)
identified a 1.5 Mb locus on ECA12 significantly associated with limbal SCC
(Pcorrected = 0.04). Sequencing the most physiologically relevant gene from this
locus, damage specific DNA binding protein 2 (DDB2), identified a missense
mutation (c.1013 C > T p.Thr338Met) that was strongly associated with limbal SCC
(P = 3.41 * 10-10 ). Genotyping 42 polymorphisms narrowed the ECA12 candidate
interval to 483 kb but did not identify another variant that was more strongly
associated. DDB2 binds to ultraviolet light damaged DNA and recruits other
proteins to perform global genome nucleotide excision repair. Computational
modeling predicts this mutation to be deleterious by altering conformation of the
beta loop involved in photolesion recognition. This DDB2 variant was also
detected in two other closely related breeds with reported cases of ocular SCC,
the Belgian and the Percheron, suggesting it may also be a SCC risk factor in
these breeds. Furthermore, in humans xeroderma pigmentosum complementation group
E, a disease characterized by sun sensitivity and increased risk of cutaneous SCC
and melanomas, is explained by mutations in DDB2. Cross-species comparison
remains to be further evaluated.
PMID- 28425626
TI - Non-cosmetic dermatological use of botulinum neurotoxin.
PMID- 28425627
TI - Relationship between parent knowledge of child sleep, and child sleep practices
and problems: A pilot study in a children's hospital cohort.
AB - AIM: To describe parent reports of sleep practices, and examine associations with
parent knowledge of child sleep, and whether children's sleep practices differ
between parents who underestimated, overestimated or accurately estimated
children's sleep needs. METHODS: Parents of children aged 2-12 years (n = 115)
attending hospital inpatient or day wards were approached and asked to report
child sleep routines, sleep problems, parent education, household income and
parent knowledge of child sleep via questionnaire. RESULTS: Younger age was
associated with earlier bedtimes and wake times, shorter sleep latencies, longer
sleep durations and greater sleep problems (P < 0.05). Parents from higher income
homes reported earlier bedtimes and wake times, shorter sleep latencies and fewer
sleep problems (P < 0.05). Parents with higher education reported shorter sleep
latencies (P < 0.05). Parents with greater knowledge about child sleep reported
earlier weekday and weekend bedtimes (r s >= 0.26) and wake times (r s >= 0.21)
and greater consistency between their child's weekend and weekday sleep routines
(P < 0.05). In comparison with parents who correctly estimated their child's
sleep needs: parents who underestimated reported later weekday bedtimes (on
average, 46 min), and longer sleep latencies (17 min); parents who overestimated
reported longer sleep latencies (22 min). These findings remained significant
when controlling for child age (P < 0.05). CONCLUSION: Parents with increased
sleep knowledge, higher incomes and higher levels of education were more likely
to report earlier bedtimes, wake times and more consistent sleep routines for
their children.
PMID- 28425628
TI - Validating the proposed ICD-11 domains: A comment on Mulder et al. (2016).
PMID- 28425629
TI - Exploring the concept of "caring cultures": A critical examination of the
conceptual, methodological and validity issues with the "caring cultures"
construct.
AB - AIMS AND OBJECTIVES: To critically examine the conceptual, methodological and
validity issues with the "caring cultures" construct. BACKGROUND: Post the
Francis Report, "caring cultures" and alternative terminology such as "culture/s
of care/caring/compassionate care" have gained prominence in the literature,
especially within a UK policy context. However, in order to understand the value
these "caring cultures" hold in terms of clinical practice, the concept itself
first needs to be understood. DESIGN: A discussion and critical examination of
the concept of "caring cultures" and associated terminology. METHODS: Grey
literature, database, library and reference list searches were conducted.
RESULTS: It is implied that "caring cultures" influence patient care. However,
evidence which verifies this assertion is limited. In this article, the concept
of "caring cultures" is deconstructed and its validity explored. An alternative
to "caring cultures" is proposed in terms of research, whereby the concept of
culture is instead explored in detail, on a microsystem level, using appropriate
methodology. CONCLUSION: The concept of "caring cultures", although attractive in
terms of its apparent simplicity, is not considered the most useful nor
appropriate phrases in terms of advancing research. Instead, research which
examines the established concept of "culture" in relation to outcomes such as
patient care, doing so with an appropriate methodology, is viewed as a more
suitable alternative. RELEVANCE TO CLINICAL PRACTICE: Clarifying concepts and
terminology relating to "caring cultures" is essential for research to progress
and the impact of culture on clinical practice to be better understood.
PMID- 28425630
TI - Earth-Abundant Chalcogenide Photovoltaic Devices with over 5% Efficiency Based on
a Cu2 BaSn(S,Se)4 Absorber.
AB - In recent years, Cu2 ZnSn(S,Se)4 (CZTSSe) materials have enabled important
progress in associated thin-film photovoltaic (PV) technology, while avoiding
scarce and/or toxic metals; however, cationic disorder and associated band
tailing fundamentally limit device performance. Cu2 BaSnS4 (CBTS) has recently
been proposed as a prospective alternative large bandgap (~2 eV), environmentally
friendly PV material, with ~2% power conversion efficiency (PCE) already
demonstrated in corresponding devices. In this study, a two-step process (i.e.,
precursor sputter deposition followed by successive sulfurization/selenization)
yields high-quality nominally pinhole-free films with large (>1 um) grains of
selenium-incorporated (x = 3) Cu2 BaSnS4-x Sex (CBTSSe) for high-efficiency PV
devices. By incorporating Se in the sulfide film, absorber layers with 1.55 eV
bandgap, ideal for single-junction PV, have been achieved within the CBTSSe
trigonal structural family. The abrupt transition in quantum efficiency data for
wavelengths above the absorption edge, coupled with a strong sharp
photoluminescence feature, confirms the relative absence of band tailing in
CBTSSe compared to CZTSSe. For the first time, by combining bandgap tuning with
an air-annealing step, a CBTSSe-based PV device with 5.2% PCE (total area 0.425
cm2 ) is reported, >2.5* better than the previous champion pure sulfide device.
These results suggest substantial promise for the emerging Se-rich Cu2 BaSnS4-x
Sex family for high-efficiency and earth-abundant PV.
PMID- 28425631
TI - Restraint stress increases prolactin-mediated phosphorylation of signal
transducer and activator of transcription 5 in the hypothalamus and adrenal
cortex in the male mouse.
AB - Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the
anterior pituitary. Its rate of secretion is primarily regulated by a negative
feedback mechanism where prolactin stimulates the activity of the
tuberoinfundibular dopaminergic (TIDA) neurones, increasing their release of
dopamine, which accesses the pituitary via the median eminence to suppress
further prolactin secretion. In addition to its well established role in
lactation, circulating prolactin is secreted in response to stress, although the
mechanism by which this is achieved or its cellular targets remains unknown. In
the present study, we show that 15 minutes of restraint stress causes an
approximately seven-fold increase in circulating prolactin concentration in male
mice. Monitoring prolactin receptor activation, using immunohistochemistry to
determine the level and distribution of tyrosine phosphorylated signal transducer
and activator of transcription 5 (pSTAT5), we show that this stress-induced
increase in prolactin interacts with both central and peripheral targets.
Restraint stress for 15 minutes significantly increased pSTAT5 staining in the
arcuate nucleus, median eminence and the zona fasciculata of the adrenal cortex.
In each case, this response was prevented by pretreating the animals with
bromocriptine to block prolactin secretion from the pituitary. Interestingly, in
contrast to many cells in the arcuate nucleus, stress reduced pSTAT5 staining of
the TIDA neurones (identified by dual-labelling for tyrosine hydroxylase). This
suggests that there is reduced prolactin signalling in these cells and thus
potentially a decline in their inhibitory influence on prolactin secretion. These
results provide evidence that prolactin secreted in response to acute stress is
sufficient to activate prolactin receptors in selected target tissues known to be
involved in the physiological adaptation to stress.
PMID- 28425633
TI - Biotechnology and Bioengineering: Volume 114, Number 6, June 2017.
PMID- 28425632
TI - Electrode assisted production of chemicals using Shewanella oneidensis.
PMID- 28425634
TI - CO2 stripping model: Gas saturated with CO2.
PMID- 28425635
TI - Adapting viral safety assurance strategies to continuous processing of biological
products.
PMID- 28425636
TI - Evolving technologies enabling patient-specific bone scaffolds.
PMID- 28425638
TI - De novo design of peptide binding antibodies.
PMID- 28425639
TI - Designing dual inhibitors of Mdm2/MdmX: Unexpected coupling of water with
gatekeeper Y100/99.
AB - Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet
dual inhibitors are challenging to design due to differences in the conformations
of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99.
Analysis of crystal structures and molecular dynamics (MD) simulations of
complexes of Mdm2 and MdmX resulted in the identification of a water molecule
with a long residence time that appears to be modulated by the conformation of
Y100/99. These observations lead us to speculate that dual inhibitors either (i)
stabilize both Mdm2 and MdmX with Y100/99 in the open conformation typically seen
in complexes of Mdm2 with p53, or (ii) the dual inhibitors are agnostic to the
conformation of Y100/99. The recently developed potent dual inhibitory stapled
peptide Atsp7041 appears to be agnostic to the conformation of the gatekeeper
residue. Proteins 2017; 85:1493-1506. (c) 2017 Wiley Periodicals, Inc.
PMID- 28425640
TI - Profiling of the silica-induced molecular events in lung epithelial cells using
the RNA-Seq approach.
AB - Silicosis is a prolonged, irreversible and incurable occupational disease, and
there is a significant number of newly diagnosed cases every year in Hong Kong.
Due to the long latency of the disease, the diagnosis can be missed until
detailed clinical examination at a later stage. For a better control of this
deadly disease, detailing the pro-inflammatory and fibrotic events in the
macrophage would be instrumental in understanding the pathogenesis of the disease
and essential for the significant biomarkers discovery. In this in vitro study,
human cell line model A549 lung epithelial cells were used. The immediate
molecular events underneath the activation of quartz silica polymorphs were
followed in a time course of 0, 0.5, 2, 8, 16 and 24 h. The transcriptome library
was prepared and subjected to RNA-Seq analysis. Data analysis was performed by
pathway analysis tools and verified by real-time PCR. The results showed that
triggered genes were mainly found in the immune response and inflammatory
pathways. An interesting finding was the association of the DNA-binding protein
inhibitor (ID) family in the silica exposure to lung cells. The linkage of ID1,
ID2 and ID3 to cancer may rationalize themselves to be the markers indicating an
early response of silicosis. However, further studies are required to consolidate
the roles of these genes in silicosis. Copyright (c) 2017 John Wiley & Sons, Ltd.
PMID- 28425642
TI - The PRIAMO study: urinary dysfunction as a marker of disease progression in early
Parkinson's disease.
AB - BACKGROUND AND PURPOSE: New venues are currently being explored to predict
disease progression in Parkinson's disease (PD), such as non-motor subtypes and
models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585
patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the
present 24-month longitudinal prospective analysis aimed to demonstrate that
urinary dysfunction is an early marker of higher motor and non-motor burden as
well as lower health-related quality of life. METHODS AND RESULTS: Multivariable
mixed-effect logistic regression models controlling for demographic and clinical
variables showed that the following NMS domains were associated with urinary
dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI)
1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013),
skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P
= 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI
1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and
respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated
that urinary dysfunction was associated with higher motor disability (coefficient
1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life
(coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95%
CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability
(coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the
first prospective longitudinal study involving a large cohort of PD patients
demonstrating the relevance of urinary dysfunction as an early marker of higher
motor and non-motor disability as well as lower health-related quality of life.
These findings support a role for urinary dysfunction as an early marker of more
severe disease progression.
PMID- 28425643
TI - Chemical Activation in Blood Serum and Human Cell Culture: Improved Ruthenium
Complex for Catalytic Uncaging of Alloc-Protected Amines.
AB - Chemical (as opposed to light-induced) activation of caged molecules is a rapidly
advancing approach to trigger biological processes. We previously introduced the
ruthenium-catalyzed release of allyloxycarbonyl (alloc)-protected amines in human
cells. A restriction of this and all other methods is the limited lifetime of the
catalyst, thus hampering meaningful applications. In this study, we addressed
this problem with the development of a new generation of ruthenium complexes for
the uncaging of alloc-protected amines with superior catalytic activity. Under
biologically relevant conditions, we achieved a turnover number >300, a reaction
rate of 580 m-1 s-1 , and we observed high activity in blood serum. Furthermore,
alloc-protected doxorubicin, as an anticancer prodrug, could be activated in
human cell culture and induced apoptosis with a single low dose (1 MUm) of the
new catalyst.
PMID- 28425641
TI - Molecular dynamics simulations of early steps in RNA-mediated conversion of
prions.
AB - The rate-limiting step in prion diseases is the initial transition of a prion
protein from its native form into a mis-folded state in which the protein not
only forms cell-toxic aggregates but also becomes infectious. Recent experiments
implicate polyadenosine RNA as a possible agent for generating the initial seed.
In order to understand the mechanism of RNA-mediated mis-folding and aggregation
of prions, we dock polyadenosine RNA to mouse and human prion models. Changes in
stability and secondary structure of the prions upon binding to polyadenosine RNA
are evaluated by comparing molecular dynamics simulations of these complexes with
that of the unbound prions.
PMID- 28425644
TI - Different effects of rotigotine and ropinirole on cholinergic transmission in the
mouse medial prefrontal cortex.
PMID- 28425645
TI - Precutting endoscopic mucosal resection for colorectal lesions.
PMID- 28425646
TI - Endoscopic detection of superficial esophagogastric junction adenocarcinoma.
PMID- 28425647
TI - Can endoscopic stone retraction be carried out even in cases with severe acute
cholangitis?
PMID- 28425648
TI - Balloon overtube can improve maneuverability of the endoscope during colorectal
endoscopic submucosal dissection.
PMID- 28425649
TI - Efficacy of hybrid endoscopic submucosal dissection (ESD) as a rescue treatment
in difficult colorectal ESD cases.
AB - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD), which provides a
higher en bloc resection rate than conventional endoscopic mucosal resection
(EMR), is considered to be a useful treatment option for large colorectal tumors.
However, colorectal ESD is not widely used because of its technical difficulty,
risk of complications and time required. To overcome these drawbacks, a simpler
modified technique, ESD with snaring (hybrid ESD), has been developed. The aim of
the present study was to retrospectively compare the safety and efficacy of
hybrid ESD and conventional ESD for colorectal tumors. METHODS: Between September
2008 and June 2016, ESD was carried out on 137 lesions and hybrid ESD on 27
lesions. All hybrid ESD cases were carried out as a rescue treatment in difficult
ESD cases. We retrospectively investigated procedure time, and the rates of en
bloc resection, perforation, bleeding, and local recurrence. RESULTS: In the
hybrid ESD group, procedure time was shorter compared with the ESD group (108 +/-
59.5 min vs 122 +/- 72.2 min), but the en bloc resection rate was lower (66.7% vs
94.2%). However, there were no significant differences in procedure time, or in
rates of en bloc resection, perforation and bleeding between the two groups.
Local recurrence did not develop in any of our cases. CONCLUSIONS: Hybrid ESD as
a rescue treatment in difficult ESD cases may be less effective for en bloc
resection of large colorectal tumors. Indication for hybrid ESD may be limited to
scheduled treatment from the outset and emergency cases with patients who present
unstable vital signs during ESD.
PMID- 28425650
TI - Current strategies for endoscopic management of acute cholangitis.
AB - BACKGROUND AND AIM: At the pancreatobiliary session of Endoscopic Forum Japan
(EFJ) 2016, current strategies for the endoscopic management of acute cholangitis
were discussed. The topics consisted of two major parts, namely endoscopic
management of acute cholangitis caused by common bile duct stones (CBDS) and
biliary stent occlusion. METHODS: Endoscopists from nine Japanese high-volume
centers along with two overseas centers participated in the questionnaires and
discussion. RESULTS: Strategies for management of cholangitis due to CBDS were
agreed upon, and the clinical guideline of acute cholangitis (Tokyo guidelines
2013) was accepted. The best timing for drainage in Grade 2 (moderate)
cholangitis urgent or early (<24 h) was inconclusive, and more data is required
on this issue. Another controversy was the feasibility of one step stone
extraction in the patient with cholangitis vs stone removal after the cholangitis
had resolved. There were various opinions with regards to the management of acute
cholangitis due to stent occlusion, and the strategies differed according to the
stricture location (distal or hilar) and stent type initially placed (Covered or
uncovered metal stent). CONCLUSION: Strategies for management of cholangitis
caused by CBD stones are well established according to the TG13. More evidence is
required before further recommendations can be made with regards to cholangitis
due to stent occlusion. We aim to clarify this in the near future with
questionnaires and consensus from experts.
PMID- 28425651
TI - Underwater endoscopic mucosal resection for a superficial polyp located at the
anastomosis after surgical colectomy.
PMID- 28425652
TI - Endoscopic findings of esophagogastric junction in children.
AB - Esophagogastric landmarks are recognizable in the same way both in children and
in adults, and palisade-shaped vessels can be observed at the distal position of
esophageal mucosa, even in infants. Few studies have been done in respect to
Barrett's esophagus (BE) in children. Incidence of endoscopically suspected BE
among all children undergoing esophagogastroduodenoscopy (EGD) is approximately
0.25-1.4%, but can be up to 9.7% in patients with gastroesophageal reflux disease
(GERD). Some data suggest that BE is an acquired disorder and point to the
possibility of a congenital component in combination with severe mucosal injury.
Recent reports noted that multilayered epithelium (ME), which shows morphological
and immunocytochemical characteristics of both squamous and columnar epithelium,
is associated with goblet cell metaplasia in adult patients with columnar-lined
esophagus. The role of ME in the development of intestinal metaplasia in children
is uncertain. Furthermore, detailed mechanisms about how short-segment BE (SSBE)
changes to long-segment BE (LSBE) are not yet well understood. Further studies
are required to understand the pathological esophagogastric junction (EGJ) and BE
in children based on reliable epidemiological data and analysis especially in
children who have reflux symptoms. Better understanding of the pediatric EGJ and
BE may allow improved diagnosis, monitoring, therapy and, therefore, prognosis of
GERD-related disorders in adulthood.
PMID- 28425654
TI - Is addition of endoscopic sphincterotomy before endoscopic biliary drainage
necessary for acute cholangitis as a result of common bile duct stones?
PMID- 28425653
TI - Endoscopic gastric mucosal atrophy distinguishes the characteristics of
superficial esophagogastric junction adenocarcinoma.
AB - BACKGROUND AND AIM: Western studies have suggested two distinct etiologies of
esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic
gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma.
The present study investigated whether endoscopic gastric mucosal atrophy can
distinguish between these two types of EGJ adenocarcinoma. METHODS: Data were
collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent
endoscopic or surgical resection at eight Japanese institutions in 2010-2015.
Clinicopathological characteristics of EGJ cancers with and without endoscopic
gastric mucosal atrophy were compared. EGJ was defined as the lower end of the
palisade vein and/or the top of the gastric folds. RESULTS: Of the 229 patients
identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter
group was younger (64 vs 70 years, P = 0.000); had a higher proportion of
patients negative for H. pylori (90% vs 47%, P < 0.0001); and had higher rates of
gastroesophageal reflux disease symptoms (43% vs 12%, P = 0.017), mucosal breaks
(25% vs 15%, P = 0.009), Barrett's esophagus (BE, 78% vs 42%, P < 0.0001), and
tumors above the EGJ (81% vs 19%, P < 0.0001) and on the upper-right side (74% vs
38%, P < 0.0001) than the former group. Multivariate analysis showed that H.
pylori positivity (odds ratio [OR] = 13.0, P < 0.001), long-segment BE (OR =
0.025, P = 0.033), and longitudinal (OR = 8.6, P = 0.001) and circumferential (OR
= 4.7, P = 0.006) tumor locations were independently associated with gastric
mucosal atrophy. CONCLUSION: Two distinct types of EGJ cancer were identified,
with and without endoscopic gastric mucosal atrophy. These types were associated
with different tumor locations.
PMID- 28425655
TI - Memorial Address for Dr Masatsugu Nakajima.
PMID- 28425656
TI - Considering the esophagogastric junction as a 'zone'.
AB - Siewert's classification of adenocarcinoma of the esophagogastric junction (EGJ)
classifies tumors anatomically for determining the appropriate surgical
technique. According to this classification, a type II tumor, true carcinoma of
the cardia, is defined as a cancer within 1 cm proximal to 2 cm distal of the
EGJ. Histological analysis indicates that the cardiac gland is present with a
high degree of frequency between 1-2 cm to the gastric side and 1-2 cm to the
esophageal side of the EGJ, which means that this zone can be considered as
neither the stomach nor the esophagus but rather as a third zone known as the
'EGJ zone'. It has been suggested that there are multiple causes for development
of adenocarcinoma in the EGJ zone. The TNM Classification of Malignant Tumours
7th Edition considers EGJ adenocarcinoma (EGJAC) occurring in the EGJ zone to be
a part of esophageal adenocarcinoma (EAC). However, recent studies have indicated
that EGJAC behaves differently from EAC and gastric carcinoma. Barrett's
esophagus is now considered an important factor in the etiology of EGJAC, but, as
yet, no studies have elucidated the differences between cancer arising from short
segment Barrett's esophagus and cancer of the gastric cardia. Thus, there is
currently no clinical relevance to subdivision of adenocarcinoma in the EGJ zone
into above or below the EGJ line.
PMID- 28425657
TI - Different time trend and management of esophagogastric junction adenocarcinoma in
three Asian countries.
AB - Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western
countries. However, in Asian countries, data on the incidence of EGJ
adenocarcinoma are evidently lacking. In the present review, we focus on the
current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan,
Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to
be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong
Kong. However, the number of cases in these countries is comparatively low
compared with Western countries. A reason for the reported difference in the
incidence and time trend of EGJ adenocarcinoma among the three countries may be
explained by two distinct etiologies: one arising from chronic gastritis similar
to distal gastric cancer, and the other related to gastroesophageal reflux
disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma.
This review also shows that there are several concerns in clinical practice for
EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been
detected at a stage not amenable to endoscopic resection. In Japan, histological
curability criteria for endoscopic resection cases have not been established. We
suggest that an international collaborative study using the same definition of
EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of
these cancers but also for improving the clinical outcome of these patients.
PMID- 28425658
TI - Endoscopic management of acute cholangitis as a result of common bile duct
stones.
AB - Acute cholangitis is infectious disease of the biliary system and potentially can
cause significant morbidity and mortality. With advances in intensive care,
antibiotic therapy advances and endoscopic and other modalities of biliary
drainage, mortality rates have significantly come down of late. Although most
cases respond to antibiotics alone, definitive therapy is required later in most
of the patients. Increased biliary pressure leads to biliovenous reflux of
bacteria and purulent bile into the circulation leading to systemic inflammation
and sepsis with subsequent organ dysfunction. Biliary decompression increases
antibiotic penetration in bile. Therefore, patients with high-risk factors and
organ dysfunction require early and urgent biliary drainage, respectively, as
they are unlikely to respond with antibiotics alone. Biliary decompression is
best achieved by endoscopic retrograde cholangiopancreatography (ERCP) compared
to percutaneous and surgical decompression. ERCP can be technically difficult and
sometimes unsuccessful especially in patients with altered anatomy and upper
gastrointestinal obstruction. Earlier percutaneous transhepatic biliary drainage
(PTBD) and surgery were the only viable options in those patients. PTBD requires
a dilated biliary system, is more invasive and cannot achieve ductal clearance in
cholangitis as a result of choledocholithiasis, whereas surgery is associated
with high morbidity and mortality. Advances in therapeutic endoscopy such as
balloon enteroscopy-guided biliary drainage or endoscopic ultrasound guided
biliary drainage have added new dimensions to endoscopic management of acute
cholangitis as a result of choledocholithiasis obviating the need for more
invasive procedures.
PMID- 28425660
TI - Endoscopic submucosal dissection for large colorectal neoplasms.
AB - BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) for colorectal
neoplasms (CRN) of >50 mm is considered technically difficult. The ITknife nanoTM
was developed specifically for ESD of CRN and esophageal superficial neoplasms;
however, only limited data are available regarding its use in this procedure.
Here we assessed the safety and efficacy of ESD using the ITknife nanoTM for
large CRN (>50 mm). METHODS: We carried out a retrospective study, including
consecutive patients with CRN larger than 50 mm that were treated by ESD between
September 2002 and August 2016 at our institution. To clarify features of the
ITknife nanoTM and to assess its safety and efficacy, we compared en
bloc/curative resection rates, complications, and resection speed between ESD
done using the Dual knifeTM with and without the ITknife nanoTM. RESULTS: We
analyzed a total of 177 ESD-treated large CRN (median tumor size, 61 mm). Among
the 133 CRN treated by ESD using the ITknife nanoTM, en bloc and curative
resection rates were 96.2% and 80.5%, respectively. Perforation occurred in eight
cases (6.0%) and delayed bleeding in four cases (3.0%). All complications were
endoscopically managed. Resection speed was significantly faster for ESD using
the ITknife nanoTM (25.3 mm2 /min) compared to using the Dual knifeTM only (19.9
mm2 /min; P = 0.02). CONCLUSIONS: Use of the ITknife nanoTM for ESD treatment of
large CRN (>50 mm) is feasible and may contribute to reduced procedure times.
Further controlled studies are needed to confirm these findings.
PMID- 28425661
TI - Preface.
PMID- 28425662
TI - Feasibility of colorectal endoscopic submucosal dissection (ESD) carried out by
endoscopists with no or little experience in gastric ESD.
AB - BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is
recommended to be carried out only by endoscopists with sufficient experience in
gastric ESD. However, early gastric carcinoma is less common in Western countries
than in Japan, and endoscopic maneuverability differs between the stomach and
colorectum. We assessed the feasibility of colorectal ESD carried out by
endoscopists with no or little experience in gastric ESD. METHODS: We analyzed en
bloc resection, R0 resection and perforation rates in 180 consecutive colorectal
ESD carried out by three endoscopists who had no or <5 cases of experience in
gastric ESD. We also identified factors associated with R0 resection failure.
RESULTS: Overall en bloc and R0 resection rates were 93.3% (168/180) and 82.2%
(148/180), respectively. All 11 cases with perforation were treated
endoscopically. Dividing 180 cases into three learning phases (early, middle, or
late phases), the en bloc and R0 resection rates increased from 88.3% and 75.0%
in the early phase to 98.3% and 88.3% in the late phase, respectively.
Perforation rate also improved from 10.0% to 3.3%. Factors associated with R0
resection failure were location at junctions (odds ratio: 6.8, 95% CI: 1.9-27.5),
preoperative factors reflecting fibrosis (5.8, 1.9-19.0), and late phase (0.2,
0.1-0.7). CONCLUSION: Endoscopists without experience in gastric ESD carried out
colorectal ESD safely. In the early and middle phases (<=40 cases), they should
treat mainly rectal lesions but may also resect lesions in the colon avoiding
flexures. Lesions located at junctions and those with preoperative factors
reflecting fibrosis should be resected after completing 40 procedures.
PMID- 28425663
TI - Management of acute cholangitis as a result of occlusion from a self-expandable
metallic stent in patients with malignant distal and hilar biliary obstructions.
AB - Acute cholangitis as a result of common bile duct stones can be managed; however,
cholangitis caused by occlusion with a biliary self-expandable metallic stent
(SEMS) in patients with an unresectable malignant biliary obstruction has not
been fully discussed. The acute cholangitis clinical guidelines (Tokyo Guidelines
2013) recommend following the same procedure as that used for cholangitis;
however, the patient's condition, including performance status, tumor extension
or staging, and prognosis must be considered. Most physicians manage cholangitis
from a SEMS occlusion using a two-step procedure. They insert endoscopic drainage
with a plastic stent or insert a nasobiliary drainage tube, which does not
exacerbate sepsis. Addition or replacement of a biliary SEMS is required in many
cases depending on the cause of the occlusion. Tumor ingrowth through the stent
mesh is common in uncovered SEMS and requires placement of another stent in an in
stent method. However, covered SEMS tends to be occluded by sludge, so it must be
replaced because of the bacterial biofilm that forms on the covering membrane.
The location of the biliary stricture (hilar or distal) should also be
considered. Strategies for managing cholangitis as a result of occlusion by a
biliary SEMS remain controversial, so prospective clinical trials are needed.
PMID- 28425664
TI - Endoscopic diagnosis of subsquamous invasion of adenocarcinoma in short-segment
Barrett's esophagus.
PMID- 28425665
TI - Standardization of endoscopic resection for colorectal tumors larger than 10 mm
in diameter.
AB - Currently, several endoscopic resection (ER) methods for colorectal tumors are
available, including polypectomy, conventional endoscopic mucosal resection
(EMR), endoscopic submucosal dissection (ESD), and modified ER. In the present
review, we mainly focus on the current status of ER for colorectal tumors as well
as the report from the Endoscopic Forum Japan (EFJ) 2016, which was held in Tokyo
in August 2016. The proposed ER methods for colorectal tumors larger than 10 mm
in diameter are as follows. (i) Pedunculated-type tumor is an indication for
polypectomy, regardless of size. (ii) Non-pedunculated-type tumor larger than 20
mm in diameter is an indication for ESD in which en bloc resection using
conventional EMR is difficult or impossible. (iii) Non-pedunculated-type tumor
from 10 mm to 20 mm in diameter is an indication for conventional EMR. However,
ESD or modified ER methods are acceptable according to the procedure and the
condition of the tumor.
PMID- 28425666
TI - Endoscopic management of acute cholangitis according to the TG13.
AB - The Tokyo Guidelines 2013 (TG13) recommend that endoscopic drainage should be the
first-choice treatment for biliary decompression in patients with acute
cholangitis. Timing of biliary drainage for acute cholangitis should be based on
the severity of the disease. For patients with severe acute cholangitis,
appropriate organ support and urgent biliary drainage are needed. For patients
with moderate acute cholangitis, early biliary drainage is needed. For patients
with mild acute cholangitis, biliary drainage is needed when initial treatment
such as antimicrobial therapy is ineffective. There are three methods of biliary
drainage: endoscopic drainage, percutaneous transhepatic drainage, and surgical
drainage. Endoscopic drainage is less invasive than the other two drainage
methods. The drainage method (endoscopic nasobiliary drainage and stenting)
depends on the endoscopist's preference but endoscopic sphincterotomy should be
selected rather than endoscopic papillary balloon dilation from the aspect of
procedure-related complications. In the TG13, balloon enteroscopy-assisted and
endoscopic ultrasound-guided biliary drainages have been newly added as specific
drainage methods. Recent studies have demonstrated their usefulness and safety.
These drainage methods will become more widespread in the future.
PMID- 28425667
TI - Soft Multifunctional Composites and Emulsions with Liquid Metals.
AB - Binary mixtures of liquid metal (LM) or low-melting-point alloy (LMPA) in an
elastomeric or fluidic carrier medium can exhibit unique combinations of
electrical, thermal, and mechanical properties. This emerging class of soft
multifunctional composites have potential applications in wearable computing, bio
inspired robotics, and shape-programmable architectures. The dispersion phase can
range from dilute droplets to connected networks that support electrical
conductivity. In contrast to deterministically patterned LM microfluidics, LMPA-
and LM-embedded elastomer (LMEE) composites are statistically homogenous and
exhibit effective bulk properties. Eutectic Ga-In (EGaIn) and Ga-In-Sn
(Galinstan) alloys are typically used due to their high conductivity, low
viscosity, negligible nontoxicity, and ability to wet to nonmetallic materials.
Because they are liquid-phase, these alloys can alter the electrical and thermal
properties of the composite while preserving the mechanics of the surrounding
medium. For composites with LMPA inclusions (e.g., Field's metal, Pb-based
solder), mechanical rigidity can be actively tuned with external heating or
electrical activation. This progress report, reviews recent experimental and
theoretical studies of this emerging class of soft material architectures and
identifies current technical challenges and opportunities for further
advancement.
PMID- 28425668
TI - Pectin, Hemicellulose, or Lignin? Impact of the Biowaste Source on the
Performance of Hard Carbons for Sodium-Ion Batteries.
AB - Hard carbons are currently the most widely used negative electrode materials in
Na-ion batteries. This is due to their promising electrochemical performance with
capacities of 200-300 mAh g-1 and stable long-term cycling. However, an abundant
and cheap carbon source is necessary in order to comply with the low-cost
philosophy of Na-ion technology. Many biological or waste materials have been
used to synthesize hard carbons but the impact of the precursors on the final
properties of the anode material is not fully understood. In this study the
impact of the biomass source on the structural and electrochemical properties of
hard carbons is unraveled by using different, representative types of biomass as
examples. The systematic structural and electrochemical investigation of hard
carbons derived from different sources-namely corncobs, peanut shells, and waste
apples, which are representative of hemicellulose-, lignin- and pectin-rich
biomass, respectively-enables understanding and interlinking of the structural
and electrochemical properties.
PMID- 28425669
TI - Dissolving Lignin in Water through Enzymatic Sulfation with Aryl
Sulfotransferase.
AB - We introduce the concept of using site-specific sulfation of various lignins for
increasing their aqueous solubility and thereby their processability. Using p
nitrophenylsulfate as a sulfate source and an aryl sulfotransferase enzyme as
catalyst, lignins are easily sulfated at ambient conditions. We demonstrate the
specific sulfation of phenolic hydroxyl groups on five different lignins: Indulin
AT (Kraft softwood), Protobind 1000 (mixed wheat straw/Sarkanda grass soda) and
three organosolv lignins. The reaction proceeds smoothly and the increase in
solubility is visible to the naked eye. We then examine the reaction kinetics,
and show that these are easily monitored qualitatively and quantitatively using
UV/Vis spectroscopy. The UV/Vis results are validated with 31 P NMR spectroscopy
of the lignin phenol groups after derivatization with phosphorylation reagent II.
In general, the results are more significant with organosolv lignins, as Kraft
and soda lignins are produced from aqueous lignocellulose extraction processes.
PMID- 28425670
TI - Electroencephalographic patterns of lithium poisoning: a study of the
effect/concentration relationships in the rat.
AB - OBJECTIVES: Lithium overdose may result in encephalopathy and
electroencephalographic abnormalities. Three poisoning patterns have been
identified based on the ingested dose, previous treatment duration and renal
function. Whether the severity of lithium-induced encephalopathy depends on the
poisoning pattern has not been established. We designed a rat study to
investigate lithium-induced encephalopathy and correlate its severity to plasma,
erythrocyte, cerebrospinal fluid and brain lithium concentrations previously
determined in rat models mimicking human poisoning patterns. METHODS: Lithium
induced encephalopathy was assessed and scored using continuous
electroencephalography. RESULTS: We demonstrated that lithium overdose was
consistently responsible for encephalopathy, the severity of which depended on
the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy
which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post
injection. Acute-on-chronically poisoned rats developed persistent and slightly
fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically
poisoned rats developed rapid-onset but gradually increasing life-threatening
encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of
the acute-on-chronically and 57% of the chronically lithium-poisoned rats
developed seizures. The relationships between encephalopathy severity and lithium
concentrations fitted a sigmoidal Emax model based on cerebrospinal fluid
concentrations in acute poisoning and brain concentrations in acute-on-chronic
poisoning. In chronic poisoning, worsening of encephalopathy paralleled the
increase in plasma lithium concentrations. CONCLUSIONS: The severity of lithium
induced encephalopathy is dependent on the poisoning pattern, which was
previously shown to determine lithium accumulation in the brain. Our data support
the proposition that electroencephalography is a sensitive tool for scoring
lithium-related neurotoxicity.
PMID- 28425672
TI - Evaluating therapeutic effect on WOMAC subscales in osteoarthritis RCTs: When
model choice matters.
AB - RATIONALE, AIMS, AND OBJECTIVES: The study aimed at developing a method for
modelling the Western Ontario and McMaster Universities index (WOMAC), accounting
for correlation between its subscales and for heterogeneity of treatment effect
(HTE), using data from 2 twin trials on knee osteoarthritis. METHOD: Two
randomized, double-blind, placebo-controlled clinical trials (twin trials).
Studies aimed at investigating the effectiveness of a pharmacological treatment
on clinical outcomes of knee osteoarthritis, measured using WOMAC index. To take
into account that the WOMAC subscales are correlated and skewed, we proposed and
compared multivariate gamma and Gaussian approaches with latent variable
capturing correlation between outcomes. Besides the latent term, the interaction
between the latent term and treatment, accounting for HTE, was further estimated.
RESULTS: Modelling the subscales by using a gamma approach accounting for
skewness of data, we found out different results compared with Gaussian models.
The main difference regarded the latent variable interacting with treatment
(accounting for unobserved heterogeneity), which is not significant for the
Gaussian approach (P value = .102) and significant in the gamma model (P value <
.002). Thus, indicating that unobserved covariates affect treatment's
performance. Additionally, plotting the observed and the estimated values of
WOMAC index of the Gaussian and gamma models, we showed that, compared with the
Gaussian, the gamma one best fits the data, especially among poor responders.
CONCLUSION: Multivariate gamma approach accounting for correlation between
outcomes and for HTE has been demonstrated to be more suitable to model WOMAC
subscales and to provide more information on effect of therapy.
PMID- 28425673
TI - Reply.
PMID- 28425671
TI - Activity-Based Probes for HECT E3 Ubiquitin Ligases.
AB - Activity-based probes (ABPs) have been used to dissect the biochemical/structural
properties and cellular functions of deubiquitinases. However, their utility in
studying cysteine-based E3 ubiquitin ligases has been limited. In this study, we
evaluate the use of ubiquitin-ABPs (Ub-VME and Ub-PA) and a novel set of E2-Ub
ABPs on a panel of HECT E3 ubiquitin ligases. Our in vitro data show that
ubiquitin-ABPs can label HECT domains. We also provide the first evidence that,
in addition to the RBR E3 ubiquitin ligase Parkin, E2-Ub-ABPs can also label the
catalytic HECT domains of NEDD4, UBE3C, and HECTD1. Importantly, the endogenous
proteasomal E3 ligase UBE3C was also successfully labelled by Ub-PA and His
UBE2D2-Ub-ABP in lysate of cells grown under basal conditions. Our findings
provide novel insights into the use of ABPs for the study of HECT E3 ubiquitin
ligases.
PMID- 28425674
TI - Comment on "Early Innovative Immersion: A Course for Pre-Medical Professions
Students Using Point-of-Care Ultrasound".
PMID- 28425675
TI - Reply.
PMID- 28425676
TI - Erratum.
PMID- 28425677
TI - Web alert: Microbial dehalogenation: An annotated selection of World Wide Web
sites relevant to the topics in environmental microbiology.
PMID- 28425678
TI - Thinking about quantity: the intertwined development of spatial and numerical
cognition.
PMID- 28425679
TI - Soft interactions and volume exclusion by polymeric crowders can stabilize or
destabilize transient structure in disordered proteins depending on polymer
concentration.
AB - The effects of macromolecular crowding on the transient structure of
intrinsically disordered proteins is not well-understood. Crowding by biological
molecules inside cells could modulate transient structure and alter IDP function.
Volume exclusion theory and observations of structured proteins suggest that IDP
transient structure would be stabilized by macromolecular crowding. Amide
hydrogen exchange (HX) of IDPs in highly concentrated polymer solutions would
provide valuable insights into IDP transient structure under crowded conditions.
Here, we have used mass spectrometry to measure HX by a transiently helical
random coil domain of the activator of thyroid and retinoid receptor (ACTR) in
solutions containing 300 g L-1 and 400 g L-1 of Ficoll, a synthetic
polysaccharide, using a recently-developed strong cation exchange-based cleanup
method [Rusinga, et al., Anal Chem 2017;89:1275-1282]. Transiently helical
regions of ACTR exchanged faster in 300 g L-1 Ficoll than in dilute buffer. In
contrast, one transient helix exchanged more slowly in 400 g L-1 Ficoll.
Nonspecific interactions destabilize ACTR helicity in 300 g L-1 Ficoll because
ACTR engages with the Ficoll polymer mesh. In contrast, 400 g L-1 Ficoll is a
semi-dilute solution where ACTR cannot engage the Ficoll mesh. At this higher
concentration, volume exclusion stabilizes ACTR helicity because ACTR is
compacted in interstitial spaces between Ficoll molecules. Our results suggest
that the interplay between nonspecific interactions and volume exclusion in
different cellular compartments could modulate IDP function by altering the
stability of IDP transient structures. Proteins 2017; 85:1468-1479. (c) 2017
Wiley Periodicals, Inc.
PMID- 28425680
TI - Adaptation to health states: Sick yet better off?
AB - Healthcare funding decisions in the UK rely on health state valuations of the
general public. However, it has been shown that there is disparity between the
valuation of the impact of hypothetical conditions on health and the reported
health by those experiencing them. Patients' adaptation to health states is among
the most common explanations for this discrepancy. Being diagnosed with a disease
appears to affect individual perception of health over time so that better
subjective health may be reported over a disease trajectory. This paper examines
adaptation to health states using a longitudinal dataset. We use four waves of
the British Cohort Study (BCS70), which tracks a sample of British individuals
since birth in 1970 and contains information on self-assessed health (SAH),
morbidity, and socioeconomic characteristics. We implement a dynamic ordered
probit model controlling for health state dependence. Results are supportive of
the existence of adaptation: Time since diagnosis has a positive impact on SAH.
Moreover, adaptation happens over relatively long durations. We do not find
significant results proving different adaptation paths for patients reporting
prior better SAH. The analysis by specific conditions generally supports the
existence of adaptation, but results are statistically significant only for a
subset of conditions.
PMID- 28425681
TI - Schedules of Controlled Substances: Temporary Placement of Six Synthetic
Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB
FUBINACA) into Schedule I. Temporary Scheduling Order.
AB - The Administrator of the Drug Enforcement Administration is issuing this
temporary scheduling order to schedule six synthetic cannabinoids: methyl 2-(1-(5
fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB
PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3
methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3
carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1
(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1
(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA,
MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3
dimethylbutanoate [MDMB-FUBINACA], and their optical, positional, and geometric
isomers, salts, and salts of isomers into schedule I pursuant to the temporary
scheduling provisions of the Controlled Substances Act. This action is based on a
finding by the Administrator that the placement of these synthetic cannabinoids
into schedule I of the Controlled Substances Act is necessary to avoid an
imminent hazard to the public safety. As a result of this order, the regulatory
controls and administrative, civil, and criminal sanctions applicable to schedule
I controlled substances will be imposed on persons who handle (manufacture,
distribute, reverse distribute, import, export, engage in research, conduct
instructional activities or chemical analysis, or possess), or propose to handle,
5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA or MDMB-FUBINACA.
PMID- 28425682
TI - Mild acute biliary pancreatitis: the timing of cholecystectomy should not exceed
index admission.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) to treat mild biliary acute
pancreatitis (MBAP) during index admission is recommended. However, the optimal
surgical timing is controversial, considering that patients are actually often
discharged from hospital and readmitted for elective cholecystectomy. Moreover,
previous studies showed an uneven patients' stratification for pancreatitis
severity. The aim of this study was to determine the outcome of patients
homogenously categorizedfor MBAP according to the newest pancreatitis
classifications, undergoing cholecystectomy with different timing. METHODS: We
retrospectively identified all patients undergoing cholecystectomy from 2008 to
2015 for MBAP, according to the 2012 Revision of the Atlanta Classification and
the Determinant-Based Classification of Acute Pancreatitis, and stratified them
in two groups: index cholecystectomy (IC) and interval-delayed cholecystectomy
(IDC, after at least 4 weeks). RESULTS: One hundred and three patients were
analyzed. IC was performed in 40 patients (38.8%) while IDC in 63 patients
(61.2%). The two groups were similar in comorbidities and pancreatitis severity
at admission. There were no differences for conversion rate, operation length,
total length of hospitalization and overall complication rates. However, IDC
patients had a 33.3% rate of re-hospitalization for recurrent biliary-pancreatic
events while waiting for the elective procedure and showed a higher rate of acute
cholecystitis at histological diagnosis than IC (11.1% vs. 0%, P=0.041).
CONCLUSIONS: Among patients affected by MBAP, homogenously assessed following the
new acute pancreatitis severity scores, the performance of cholecystectomy during
the index admission is the best treatment option in order to avoid further
undesired hospitalizations for recurrent biliary/pancreatic events while waiting
for surgery.
PMID- 28425683
TI - Preservation of duodenal passage as a determinant of short- and long-term quality
of life in gastric cancer patients after total gastrectomy.
AB - BACKGROUND: The aim of this prospective study was to compare subjective and
objective quality of life (QoL) of gastric cancer patients after total
gastrectomy with and without preservation of the duodenal passage during short-
and long-term follow-up. METHODS: The study included 68 patients, among them 37
(54%) persons subjected to total gastrectomy with Roux-Y reconstruction (R-Y
group) and 31 (46%) individuals in whom gastrectomy was followed by formation of
Henley-Longmire loop (H-L group). Subjective and objective QoL was determined 1
and 10 years postsurgery. During each visit, subjective QoL was determined with
EORTC QLQ-C30 questionnaire, along with markers of nutritional status and self
reported incidence of symptoms specific to postgastrectomy syndrome. RESULTS: The
two groups did not differ significantly in terms of their subjective QoL and
markers of nutritional status at 1 and 10 years postsurgery, and none of these
parameters underwent significant changes between the first and second evaluation.
Patients from R-Y group reported subjective weight loss significantly more often
during both visits, and individuals from H-L group significantly more often
complained on postprandial diarrhea during long-term follow-up. Moreover, both
groups showed an increase in the incidence of postprandial vomiting between the
first and second evaluation. CONCLUSIONS: QoL of gastric cancer patients
subjected to total gastrectomy stabilizes at relatively high level within a year
from the surgery. Preservation of the duodenal passage does not exert a
beneficial effect on both objective and subjective QoL after total gastrectomy.
PMID- 28425684
TI - Single versus two-operator endoscopic biliary cannulation technique: a
multicenter matched-case analysis.
AB - BACKGROUND: The aim of this study was to compare the outcomes of physician
controlled, using both long and short endoscopic-retrograde
cholangiopancreatography wire systems, and assistant-controlled guide-wire
biliary cannulation techniques, and to perform a literature review on this topic.
METHODS: The endoscopic databases of three Endoscopic Centers were reviewed to
identify all consecutive patients with an intact papilla who, between July 2013
and December 2014, underwent an endoscopic-retrograde-cholangiopancreatography. A
total of 240 patients (80 for each group) were matched 1:1, by gender, age and
indications for procedure and were included in the analysis. All articles of
physician-controlled vs. assistant-controlled guide-wire biliary cannulation
techniques, were extracted up to December 2016, and included in the review.
RESULTS: There were no statistically significant differences in primary and final
(using rescue technique) cannulation rate between the three groups. The mean
primary cannulation time and overall cannulation time were shorter in the two
groups of physician-controlled guide-wire compared to the assistant-controlled
guide-wire group, but the difference was not statistically significant. The total
procedure time did not differ significantly between the three groups, but the
physician-controlled guide-wire using short wire system was associated with a
trend toward a shorter time compared to the other two techniques. There were no
statistically significant differences in complication rates between the three
groups. Three pertinent articles were included in the review. The mean procedure
success and complication rates were 92% and 7%, respectively. CONCLUSIONS: The
literature review and our results show that all these techniques have equally
efficacy and safety for guide-wire cannulation.
PMID- 28425685
TI - Is T4 colon cancer still an absolute contraindication to laparoscopic surgery?
AB - BACKGROUND: Laparoscopic surgery is widely accepted for colon cancer resection.
However, T4 colon cancers have been considered an absolute contraindication to
laparoscopic resection. The aim of this study is to evaluate if laparoscopy
should still be considered an absolute contraindication to T4 colon cancer, based
on a monocenter series recorded in a prospective database. METHODS: Of 77
patients undergoing elective resection for T4 colon cancer between 2004 and 2015,
39 were performed laparoscopically and were compared to 38 having undergone open
resection. RESULTS: Patient age and American Society of Anesthesiologists score
were comparable. Eleven patients initially treated laparoscopically were
converted to an open approach (28.2%). There were no statistically significant
differences between laparoscopy vs. open concerning tumor stage, R0 resections,
operative time, metastatic rate, local recurrence rate or hospital stay.
Laparoscopic surgery was associated with less postoperative complications than
open surgery (25.6% vs. 52.6%; P=0.020). No statistically significant difference
was found with regards to the 3-year overall, tumor-specific and disease-free
survivals. CONCLUSIONS: As there were less postoperative complications, while
tumor stage, operative time, hospital stay, R0 resection and survival rates after
laparoscopic resection for T4 colonic cancer were not statistically significantly
different compared to open surgery, T4 colon cancers are no longer an absolute
contraindication to laparoscopic resection in our hospital.
PMID- 28425686
TI - If time matters: a multicenter review of minimally-invasive hernia repair in 7176
cases.
AB - BACKGROUND: In endoscopic hernia repair totally extraperitoneal approach (TEP)
and transabdominal preperitoneal approach (TAPP) are seen as equivalent surgical
techniques in quality, but not in procedure-time. METHODS: We compared the two
most common procedures in endoscopic hernia surgery. Focusing on the duration of
the surgical procedure, we analyzed 7176 endoscopic hernia operations in 25
hospitals retrospectively and compared it to the literature. RESULTS: In our
study TEP (N.=2799) took on average 59 minutes, TAPP (N.=4377) took 67.5 minutes,
thus with a significant difference (P=0.043). In high volume centres this
difference was even bigger. As there are few consistent advantages of one of the
procedures in general, the procedure' s duration becomes more important.
CONCLUSIONS: If time is the main reason, the TEP procedure takes on average 8.5
minutes less time, so it can be more cost-effective.
PMID- 28425687
TI - Patient Protection and Affordable Care Act; Market Stabilization. Final rule.
AB - This rule finalizes changes that will help stabilize the individual and small
group markets and affirm the traditional role of State regulators. This final
rule amends standards relating to special enrollment periods, guaranteed
availability, and the timing of the annual open enrollment period in
theindividual market for the 2018 plan year; standards related to network
adequacy and essential community providers for qualified health plans; andthe
rules around actuarial value requirements.
PMID- 28425688
TI - Pediatric epilepsy and psychiatric comorbidity: preliminary observational data
from a prospective study.
AB - BACKGROUND: Several studies have confirmed psychiatric comorbidity and a worse
quality of life in children with epilepsy, but the clinical assessment and
monitoring of these patients often pays insufficient attention to their
psychological aspects alongside their neurological issues. The present study aims
to describe the distribution of psychopathologies and their clinical evolution
over 18 months in a sample of children followed up since the onset of their
epilepsy. METHODS: After being diagnosed with epilepsy, 49 subjects (age 4-18y)
were followed up with psychiatric and psychological assessments based on the use
of dimensional and categorical psychometric tools. RESULTS: Baseline data (T0)
showed a high psychiatric comorbidity in epileptic children, with a prevalence of
anxious-depressive disorders and attention deficit hyperactivity disorder (ADHD).
Specifically, generalized epilepsy, antiepileptic drug intake and more frequent
seizures were associated with externalizing problems, while focal epilepsy was
linked with anxiety disorders. The follow-up at 18 months revealed that about 90%
of patients had achieved a reduction in the frequency and duration of their
seizures, but their psychopathological assessment remained virtually unchanged.
The patients' psychological issues had warranted psychotherapy in 43% of cases.
CONCLUSIONS: When children or adolescents are diagnosed with epilepsy, their
psychopathological profile should be investigated and monitored over time.
Psychotherapy and/or psychopharmacological treatments should be offered to
pediatric patients with epilepsy who suffer from emotional-behavioral disorders.
PMID- 28425689
TI - Normal values of creatine kinase and of MB-creatine kinase at birth in healthy
babies.
AB - BACKGROUND: Today, few studies have been accomplished in order to determine serum
creatine kinase (CK) activity in newborns by considering small groups of babies
and without taking into account gestational age (GA) differences. Some authors
have demonstrated that neonatal CK activity value at birth is higher than the
normal range of CK activity considering for adults or older children. The
objective of this study is to assess normal values of CK and MB-CK in neonatal
blood, according to babies' GA. METHODS: We retrieved the clinical files of 140
babies admitted into Siena Hospital NICU in a 2-years period, when CK was
assessed routinely to all babies at birth. We selected files from 114 newborns
and we divided the cohort into group A (non-stressed; n=41) and group B
(stressed; n=73) on the basis of Apgar score and signs of neurological lesions.
We compared CK and MB-CK values in the two groups according to GA. RESULTS: Mean
CK value of the 41 non-stressed babies' samples: 413 IU/L (232 SD). CK
significantly increases with GA. No differences are present in total CK activity
between stressed vs non-stressed babies; but a significant difference appears in
these two groups for MB-CK (mean values: 456 vs 175 IU/L). CONCLUSIONS: This is
the first study that compares CK and MB-CK values at birth according to the GA of
the babies. CK values increase with GA, and stressed babies have higher MB-CK
values than the non-stressed babies. These reference values are important for
clinical practice.
PMID- 28425690
TI - What's new with common genetic skin disorders?
AB - Familiar genetic disorders such as neurofibromatosis type I (NF1), tuberous
sclerosis complex (TSC), oculocutaneous albinism (OCA), basal cell nevus syndrome
(BCNS), incontinentia pigmenti, ichthyosis, and epidermolysis bullosa (EB) have
prominent, cutaneous manifestations. This review describes recent advances in
knowledge concerning the pathophysiology, diagnosis, and treatment of these skin
features. Specifically, clinical diagnostic criteria for incontinentia pigmenti,
ichthyosis, and tuberous sclerosis have been updated. Additionally, there have
been considerable advancements in the technology used in the molecular diagnoses
of these conditions. In the case of TSC, the discovery that a portion of TSC
mutations are missed due to mosaicism is driving the development of new
diagnostic methods. Also, scientists are also seeking minimally invasive methods
of genetic diagnosis, as in the case of using hair follicles to diagnose
autosomal recessive congenital ichythosis (ARCI). Finally, there are innovative
targeted medical therapies being developed that serve as promising tools in the
care of patients afflicted with conditions including ichthyosis and EB.
PMID- 28425692
TI - Antitrust Law--Hospital Mergers--Third Circuit Clarifies Geographic Market
Definition and Raises Bar for Efficiencies Defense.
PMID- 28425691
TI - Health implications of new-age technologies: a systematic review.
AB - INTRODUCTION: New-age technologies are ubiquitous in the lives of adolescents.
Recent trends in media use suggest that adolescents are spending more time than
ever engaging with technologies, and are able to do so in virtually all settings
at any time. Given that new-age technologies are so heavily integrated within the
daily life of adolescents, the health risks and benefits they offer must be
closely examined. EVIDENCE ACQUISITION: In this systematic review, we present
recent literature related to the implications of new-age technologies on
adolescent health. A total of 94 articles published since 2006 were collected
using PubMed and Google Scholar on the most popular new-age technologies among
adolescents: the internet, television, cell phones, and video games. EVIDENCE
SYNTHESIS: The current body of research highlights several health risks related
to these technologies. Nearly all have the potential for addiction, which can
result in other symptoms and impair one's daily life. Excessive use can affect
several components of health, such as quality of sleep, body composition, and
mental well-being, and certain practices (viewing pornography, sexting) can lead
to risky sexual behaviors. However, the technologies discussed in the present
review also have tremendous potential to promote adolescent health. CONCLUSIONS:
Pediatricians must educate parents and patients on how to safely use technology
to minimize the potentially harmful outcomes.
PMID- 28425693
TI - Supporting Higher Education for People with Disabilities.
PMID- 28425694
TI - State Newborn Health Screening Policies.
PMID- 28425695
TI - Reduced Graphene Oxide-Containing Smart Hydrogels with Excellent Electro-Response
and Mechanical Properties for Soft Actuators.
AB - A novel reduced graphene oxide/poly(2-acrylamido-2-methylpropanesulfonic acid-co
acrylamide) (rGO/poly(AMPS-co-AAm)) nanocomposite hydrogel that possesses
excellent electro-response and mechanical properties has been successfully
developed. The rGO nanosheets that homogeneously dispersed in the hydrogels could
provide prominent conductive platforms for promoting the ion transport inside the
hydrogels to generate significant osmotic pressure between the outside and inside
of such nanocomposite hydrogels. Thus, the electro-responsive rate and degree of
the hydrogel for both deswelling and bending performances become rapid and
remarkable. Moreover, the enhanced mechanical properties including both the
tensile strength and compressive strength of rGO/poly(AMPS-co-AAm) hydrogels are
improved by the hydrogen-bond interactions between the rGO nanosheets and polymer
chains, which could dissipate the strain energy in the polymeric networks of the
hydrogels. The proposed rGO/poly(AMPS-co-AAm) nanocomposite hydrogels with
improved mechanical properties exhibit rapid, significant, and reversible electro
response, which show great potential for developing remotely controlled electro
responsive hydrogel systems, such as smart actuators and soft manipulators.
PMID- 28425696
TI - Granadilla-Inspired Structure Design for Conversion/Alloy-Reaction Electrode with
Integrated Lithium Storage Behaviors.
AB - Conversion/alloy-reaction electrode materials promise much higher energy density
than the commonly used ones based on intercalation chemistries. However, the low
electronic conductivity and, specially, the large volume expansion upon
lithiation hinder their practical applications. Here, for the first time, a
unique granadilla-inspired structure was designed to prepare the conversion/alloy
reaction anode of carbon coated tin/calcium tin oxide (C@void@Sn/CaSnO3) ternary
composite. The granadilla-inspired structure ensures the intimate contact between
the Sn/CaSnO3 nanoparticles and the carbon matrix, providing not only conductive
networks for electron transport and a short distance for Li+ diffusion but also
effective space for the electrode volume expansion toward conversion/alloy
reaction. Moreover, the unique structure possesses abundant solid-solid
interfaces between the three components as well as solid-liquid interfaces
between nanoparticles and electrolyte, contributing to a large percent (58%) of
interfacial charge (thus capacity). The integration of alloy-reaction, conversion
reaction, and interfacial lithium storage endows the hybrid electrode with a high
capacity and long cycling life, holding great promise for next-generation high
capacity lithium-ion batteries.
PMID- 28425698
TI - Dispersion-Assembly Approach to Synthesize Three-Dimensional Graphene/Polymer
Composite Aerogel as a Powerful Organic Cathode for Rechargeable Li and Na
Batteries.
AB - Polymer cathode materials are promising alternatives to inorganic counterparts
for both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) due to
their high theoretical capacity, adjustable molecular structure, and strong
adaptability to different counterions in batteries, etc. However, they suffer
from poor practical capacity and low rate capability because of their
intrinsically poor conductivity. Herein, we report the synthesis of self
assembled graphene/poly(anthraquinonyl sufide) (PAQS) composite aerogel (GPA)
with efficient integration of a three-dimensional (3D) graphene framework with
electroactive PAQS particles via a novel dispersion-assembly strategy which can
be used as a free-standing flexible cathode upon mechanical pressing. The entire
GPA cathode can deliver the highest capacity of 156 mAh g-1 at 0.1 C (1 C = 225
mAh g-1) with an ultrahigh utilization (94.9%) of PAQS and exhibits an excellent
rate performance with 102 mAh g-1 at 20 C in LIBs. Furthermore, the flexible GPA
film was also tested as cathode for SIBs and demonstrated a high-rate capability
with 72 mAh g-1 at 5 C and an ultralong cycling stability (71.4% capacity
retention after 1000 cycles at 0.5 C) which has rarely been achieved before. Such
excellent electrochemical performance of GPA as cathode for both LIBs and SIBs
could be ascribed to the fast redox kinetics and electron transportation within
GPA, resulting from the interconnected conductive framework of graphene and the
intimate interaction between graphene and PAQS through an efficient wrapping
structure. This approach opens a universal way to develop cathode materials for
powerful batteries with different metal-based counter electrodes.
PMID- 28425697
TI - Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered
Protein:Target Affinity by Altering the Lifetime of the Bound Complex.
AB - Appropriate integration of cellular signals requires a delicate balance of ligand
target binding affinities. Increasing the level of residual structure in
intrinsically disordered proteins (IDPs), which are overrepresented in these
cellular processes, has been shown previously to enhance binding affinities and
alter cellular function. Conserved proline residues are commonly found flanking
regions of IDPs that become helical upon interacting with a partner protein.
Here, we mutate these helix-flanking prolines in p53 and MLL and find opposite
effects on binding affinity upon an increase in free IDP helicity. In both cases,
changes in affinity were due to alterations in dissociation, not association,
rate constants, which is inconsistent with conformational selection mechanisms.
We conclude that, contrary to previous suggestions, helix-flanking prolines do
not regulate affinity by modulating the rate of complex formation. Instead, they
influence binding affinities by controlling the lifetime of the bound complex.
PMID- 28425699
TI - Synthesis of NPN-Coordinated Tantalum Alkyl Complexes and Their Hydrogenolysis:
Isolation of a Terminal Tantalum Hydride Incorporating a Doubly Cyclometalated
NPN Scaffold.
AB - The closely related benzylene-linked diaminophosphines PhP(CH2C6H4-o-NHPh)2 (AH2)
and PhP(C6H4-o-CH2NHXyl)2 (BH2 with Xyl = 3,5-Me2C6H3) were employed for the
synthesis of tantalum(V) alkyls, which were then studied with respect to
hydrogenolysis. In the case of AH2, the tantalum trimethyl complex [Ta(A)Me3] (1)
and the tantalum hydrocarbyl complex [Ta(A)(CH2SiMe3)(eta2-EtC=CEt)] (2) were
prepared from the ligand's dilithium salt (A)Li2(diox). Upon hydrogenolysis of 1
and 2, the formation of methane and SiMe4, respectively, was observed, but well
defined tantalum hydrides could not be detected. In the case of BH2, the
cyclometalated species [Ta(B*)(NMe2)2] (3 with B* = kappa4-N,P,N,C-(PhP(C6H4-o
CH2NXyl)(C6H4-o-CHNXyl))3-) was isolated and converted to the corresponding
diiodo species [Ta(B*)I2] (4). Treatment of 4 with LiCH2SiMe3 resulted in the
isolation of the corresponding dialkyl complex [Ta(B*)(CH2SiMe3)2] (5), which was
converted to the doubly cyclometalated monoalkyl complexes
[Ta(B**)(CH2SiMe3)(PMe3)] (6 with B** = kappa5-C,N,P,N,C-(PhP(C6H4-o-CHNXyl)2)4-)
and [Ta(B**)(CH2SiMe3)(dmpe)] (7) via reaction with PMe3 and dmpe, respectively.
In contrast to 5 and 6, 7 was found to react cleanly with dihydrogen to afford
the corresponding terminal tantalum(V) hydride [Ta(B**)(H)(dmpe)] (8). Upon
reaction of 7 with D2, the deuteride [Ta(d2-B**)(D)(dmpe)] (9) was obtained and
found to contain deuterium atoms in the methine positions of both
tantalaaziridine subunits. The partially deuterated derivatives
[Ta(B**)(D)(dmpe)] (10) and [Ta(d2-B**)(H)(dmpe)] (11) were generated via
reaction of 8 and 9 with PhSiD3 and PhSiH3, respectively. Prior to the addition
of gaseous D2 or H2, no H/D scrambling was observed in 10 or 11, indicating that
the exchange of the methine positions proceeds via addition of D2 or H2 across
the tantalaaziridine Ta-C bonds.
PMID- 28425700
TI - Reaction of the Tricyanoborate Dianion [B(CN)3]2- with HgCl2.
AB - The very reactive [B(CN)3]2- dianion has a strongly nucleophilic boron atom and
can be used for the synthesis of tricyanoborates, which otherwise are difficult
to access. Herein the reaction of this anion with HgCl2 is reported. The main
product is the anionic mercury complex [Hg(B(CN)3)2]2-. Heteronuclear NMR
spectroscopic experiments shows that the reaction proceeds via the intermediate
[ClHgB(CN)3]2-. Even though [Hg(B(CN)3)2]2- is the main product, it is difficult
to obtain it in pure form, because it slowly decomposes in the presence of water
and air to [(NC)HgB(CN)3]-. All three anions were fully characterized by
hetereonuclear NMR spectroscopy (11B, 13C, and 199Hg). Single-crystal X-ray
diffraction studies of the salts K[ClHgB(CN)3], [Ph4P]2[Hg(B(CN)3)2],
K[(NC)HgB(CN)3], and [Ph4P][(NC)HgB(CN)3] revealed linear coordination
environments around mercury for all anions. The Hg-B bonds range from 2.219(5) A
in [Hg(B(CN)3)2]2- to 2.148(11) A in [ClHgB(CN)3]-, are in accord with the sum of
the covalent radii of mercury and boron, and can be described as covalent single
bonds. A comparison with related complexes indicates that the [B(CN)3]2- dianion
is a stronger ligand than chloride, cyanide, or carbenes. [Hg(B(CN)3)2]2-
hydrolyses in solution only in the presence of oxygen. It is suggested that cis
[Hg(OH)2(B(CN)3)2]2- is formed as a very unstable intermediate, which decomposes
very fast to [(NC)HgB(CN)3]- and other products. The anion cis
[Hg(OH)2(B(CN)3)2]2- would contain mercury in the unusual oxidation state +IV.
Quantum-chemical calculations were performed to support this assumption.
PMID- 28425702
TI - Oxidatively Induced C-H Activation at High Valent Nickel.
AB - This communication describes a series of oxidatively induced intramolecular arene
C-H activation reactions of NiII model complexes to yield NiIV sigma-aryl
products. These reactions proceed within 10 min at room temperature, which
represents among the mildest conditions reported for C-H cleavage at a Ni center.
A combination of density functional theory and preliminary experimental
mechanistic studies implicate a pathway involving initial 2e- oxidation of the
NiII starting materials by the F+ transfer reagent N-fluoro-2,4,6
trimethylpyridinium triflate followed by triflate-assisted C-H cleavage at NiIV
to yield the products.
PMID- 28425701
TI - Effects of Glutamate Receptor Activation on Local Oxygen Changes.
AB - Glutamate is ubiquitous throughout the brain and serves as the primary excitatory
neurotransmitter. Neurons require energy to fire, and energetic substrates (i.e.,
O2, glucose) are renewed via cerebral blood flow (CBF) to maintain metabolic
homeostasis. Magnetic resonance brain functionality studies rely on the
assumption that CBF and neuronal activity are coupled consistently throughout the
brain; however, the origin of neuronal activity does not always coincide with
signals indicative of energy consumption (e.g., O2 decreases) at high spatial
resolutions. Therefore, relationships between excitatory neurotransmission and
energy use must be evaluated at higher resolutions. In this study, we showed that
both endogenously released and exogenously ejected glutamate decrease local
tissue O2 concentrations, but whether hyperemic O2 restoration followed depended
on the stimulus method. Electrically stimulating the glutamatergic
corticostriatal pathway evoked biphasic O2 responses at striatal terminals: first
O2 decreased, then concentrations increased above baseline. Using iontophoresis
to locally eject ionotropic glutamate receptor antagonists revealed that these
receptors only influenced the O2 decrease. We compared electrical stimulation to
iontophoretic glutamate stimulation, and measured concurrent single-unit activity
and O2 to limit both stimulation and recordings to <50 MUm radius from our
sensor. Similarly, iontophoretic glutamate delivery elicited monophasic O2
decreases without subsequent increases.
PMID- 28425703
TI - Influence of the Oxygen Electrode Open Ratio and Electrolyte Evaporation on the
Performance of Li-O2 Batteries.
AB - This study experimentally investigates and numerically simulates the influence of
the cathode electrode open ratio (ratio of oxygen-opening area to the total
electrode surface area) on the performance of Li-O2 batteries at various
discharge current densities. At the current density of 0.1 mA/cm2, the maximum
discharge capacity is achieved at 25% open ratio among the tested open ratios (0
100%). As the open ratio increases from 25% to 100%, the specific discharge
capacity decreases from 995 to 397 mA h/gcarbon. A similar trend is observed at
0.3 mA/cm2, while the maximum discharge capacity is obtained at 3% open ratio
among the tested open ratios. The model that assumes the electrode is always
fully saturated by the electrolyte does not obtain similar trends with
experimental results, while the model that considers electrolyte loss by
evaporation and the volume change of the solid obtains the same trend with
experimental observations. The open ratio governs not only availability of oxygen
but also the evaporation of the electrolyte and the contact resistance. The
faster evaporation of the electrolyte at a higher open ratio can be the main
reason for the decrease of the discharge capacity, especially when the open ratio
is relatively high (above 25%). Meanwhile, the contact resistance of the battery,
measured by the electrochemical impedance spectroscopy (EIS), increases from 3.97
to 7.02 Omega when the open ratio increased from 3% to 95%. The increase of the
Ohmic overpotential, however, is negligible (on the order of millivolts) because
of the low discharge and charge current rates (on the order of 0.1 mA).
PMID- 28425704
TI - An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while
Remodeling Mature Amyloid Fibrils.
AB - Protein aggregation is a hallmark of several neurodegenerative diseases,
including Alzheimer's and Parkinson's diseases. It has been shown that lysine
residues play a key role in the formation of these aggregates. Thus, the ability
to disrupt aggregate formation by covalently modifying lysine residues could lead
to the discovery of therapeutically relevant antiamyloidogenesis compounds.
Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit
amyloid aggregation. Using alpha-synuclein and Abeta1-40 as model amyloidogenic
proteins, we observed that IQ was able to react with lysine residues and reduce
amyloid aggregation. We also observed that IQ reacted with free amines within the
amyloid fibrils preventing their dissociation and seeding capacity.
PMID- 28425705
TI - Facile Aqueous-Phase Synthesis of the PtAu/Bi2O3 Hybrid Catalyst for Efficient
Electro-Oxidation of Ethanol.
AB - In this work, we present a facile aqueous-phase synthesis of a hybrid catalyst
consisting of PtAu alloy supported on Bi2O3 microspheres. Multistep reduction of
HAuCl4 and K2PtCl4 salts on Bi2O3 and subsequent annealing lead to the formation
of this hybrid catalyst. To the best of our knowledge, this is the first report
of using Bi2O3 as a catalyst support in fuel cell applications. The material was
characterized by powder X-ray diffraction and various microscopic techniques.
This composite showed remarkable activity as well as stability toward the electro
oxidation of ethanol in comparison to commercially available Pt/C. The order of
the reactivity was found to be commercial Pt/C (50.4 mA/m2mgPt-1) < Pt/Bi2O3(10)
(108 mA/m2mgPt-1) < PtAu/Bi2O3(10) (459 mA/m2mgPt-1). The enhancement in the
activity can be explained through cooperative effects, namely, ligand effects of
gold and Bi2O3 support, which helps in removing carbon monoxide molecules to
avoid the poisoning of the Pt active sites.
PMID- 28425706
TI - Allosteric Autoinhibition Pathway in Transcription Factor ERG: Dynamics Network
and Mutant Experimental Evaluations.
AB - Allosteric autoinhibition exists in many transcription factors. The ERG proteins
exhibit autoinhibition on DNA binding by the C-terminal and N-terminal inhibitory
domains (CID and NID). However, the autoinhibition mechanism and allosteric
pathway of ERG are unknown. In this study we intend to elucidate the residue
level allosteric mechanism and pathway via a combined approach of computational
and experimental analyses. Specifically computational residue-level fluctuation
correlation data was analyzed to reveal detailed dynamics signatures in the
allosteric autoinhibition process. A hypothesis of "NID/CID binding induced
allostery" is proposed to link similar structures and different protein
functions, which is subsequently validated by perturbation and mutation analyses
in both computation and experiment. Two possible allosteric autoinhibition
pathways of L286-L382-A379-G377-I360-Y355-R353 and L286-L382-A379-G377-I360-Y355-
A351-K347-R350 were identified computationally and were confirmed by the
computational and experimental mutations. Specifically we identified two mutation
sites on the allosteric inhibition pathways, L286P/Q383P (NID/CID binding site)
and I360G (pathway junction), which completely restore the wild type DNA binding
affinity. These results suggest that the putative protein structure-function
relationship may be augmented with a general relationship of protein
"structure/fluctuation-correlation/function" for more thorough analyses of
protein functions.
PMID- 28425707
TI - Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin
Structural Fold.
AB - Granulins are a family of protein growth factors that are involved in cell
proliferation. An orthologue of granulin from the human parasitic liver fluke
Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates
wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle
for clinical development. To identify the bioactive region(s) of Ov-GRN-1, four
truncated N-terminal analogues were synthesized and characterized structurally
using NMR spectroscopy. Peptides that contained only two native disulfide bonds
lack the characteristic granulin beta-hairpin structure. Remarkably, the
introduction of a non-native disulfide bond was critical for formation of beta
hairpin structure. Despite this structural difference, both two and three
disulfide-bonded peptides drove proliferation of a human cholangiocyte cell line
and demonstrated potent wound healing in mice. Peptides derived from Ov-GRN-1 are
leads for novel wound healing therapeutics, as they are likely less immunogenic
than the full-length protein and more convenient to produce.
PMID- 28425708
TI - Revealing Multiple Pathways in T4 Lysozyme Substep Conformational Motions by
Single-Molecule Enzymology and Modeling.
AB - Enzyme conformational dynamics play crucial roles in catalytic functions.
Obtaining molecular level insights into the conformational transition dynamics of
enzyme-substrate complex from the inactive state to the active state is
fundamental for understanding enzymatic function and dynamics. Here, we report
our progress on the real-time conformational transition dynamics of T4 lysozyme
under enzymatic reactions using single-molecule fluorescence resonance energy
transfer. The time duration in forming the active enzyme-substrate complex state
(ES*) shows distinctive Poisson and non-Poisson statistics, including exponential
and nonexponential, convoluted Poisson distributions, and Gaussian-like
distributions. These complex dynamic behaviors of T4 lysozyme are in excellent
agreement with a Markov dynamic simulation and a transition steps modeling.
Specifically, we are able to obtain mechanistic understandings: (1) Transiting
from enzyme (E) to ES*, T4 lysozyme hinge-bending conformational changes undergo
multiple steps following multiple pathways. In the case of shortest pathway, this
transition only requires one elementary transition or reaction step. (2) Substep
conformational motions, associating with multiple nuclear coordinates and a
common projected FRET-sensitive nuclear coordinate, can give rise to multiple
conformational intermediate states. (3) The consequence of the multiple pathways,
intermediate states, and nuclear coordinates is the time bunching effect; i.e.,
time durations of conformational changes tend to bunch in a narrowly distributed
time window. The physical picture of multiple intermediate states along with
bunching effect suggests that the conformational dynamics of T4 lysozyme shows a
complementary characteristic behavior of convoluted enzyme conformation selection
and induced-fit dynamics driven by substrate-enzyme interactions.
PMID- 28425710
TI - Solvation Structure of 1,3-Butanediol in Aqueous Binary Solvents with
Acetonitrile, 1,4-Dioxane, and Dimethyl Sulfoxide Studied by IR, NMR, and
Molecular Dynamics Simulation.
AB - The solvation structure of 1,3-butanediol (1,3-BD) in aqueous binary solvents of
acetonitrile (AN), 1,4-dioxane (DIO), and dimethyl sulfoxide (DMSO) at various
mole fractions of organic solvent xOS has been clarified by means of infrared
(IR) and 1H and 13C NMR. The change in the wavenumber of O-H stretching vibration
of 1,3-BD in the three systems suggested that water molecules which are initially
hydrogen-bonded with the 1,3-BD hydroxyl groups in the water solvent (xOS = 0)
are more significantly replaced by organic solvent molecules in the order of DMSO
? DIO > AN. This agrees with the order of the electron donicities of the organic
solvents. The 1H and 13C chemical shifts of 1,3-BD also revealed the most
remarkable replacement of water molecules on the hydroxyl groups by DMSO. In
contrast to the DMSO system, the O-H vibration band of 1,3-BD in the AN and DIO
systems suggested the formation of the intramolecular hydrogen bond between the
two hydroxyl groups of 1,3-BD above xOS = ~0.9. To further evaluate the
intramolecular hydrogen bonding of 1,3-BD in AN-water binary solvents, molecular
dynamics (MD) simulations and NMR experiments for spin-lattice relaxation times
T1 and 1H-1H nuclear Overhauser effect (NOE) were conducted on 1,3-BD in the AN
system. These results showed the intramolecular hydrogen bond within 1,3-BD in
the AN-water binary solvents in the high AN mole fraction range of xAN > 0.9.
Especially, the pair correlation functions g(r) of the OH-O interactions of 1,3
BD obtained from the MD simulations indicated that the intramolecular hydrogen
bond remarkably increases in the AN solvent as the xAN rises to the unity.
PMID- 28425711
TI - Influence of Surfactants on Sodium Chloride Crystallization in Confinement.
AB - We study the influence of different surfactants on NaCl crystallization during
evaporation of aqueous salt solutions. We found that at concentrations of sodium
chloride close to saturation, only the cationic surfactant CTAB and the nonionic
surfactant Tween 80 remain stable. For the nonionic surfactant, the high
concentration of salt does not significantly change either the critical micellar
concentration (CMC) or the surface tension at the CMC; for the cationic
surfactant, the CMC is reduced by roughly 2 orders of magnitude upon adding the
salt. The presence of both types of surfactants in the salt solution delays the
crystallization of sodium chloride with evaporation. This, in turn, leads to high
supersaturation which induces the rapid precipitation of a hopper crystal in the
bulk. The crystallization inhibitor role of these surfactants is shown to be
mainly due to the passivation of nucleation sites at both liquid/air and
solid/liquid interfaces rather than a change in the evaporation rate which is
found not to be affected by the presence of the surfactants. The adsorption of
surfactants at the liquid/air interface prevents the crystallization at this
location which is generally the place where the precipitation of sodium chloride
is observed. Moreover, sum frequency generation spectroscopy measurements show
that the surfactants are also present at the solid/liquid interface. The
incorporation of the surfactants into the salt crystals is investigated using a
novel, but simple, method based on surface tension measurements. Our results show
that the nonionic surfactant Tween 80 is incorporated in the NaCl crystals but
the cationic surfactant CTAB is not. Taken together, these results therefore
allow us to establish the effect of the presence of surfactants on sodium
chloride crystallization.
PMID- 28425709
TI - Beyond Structural Biology to Functional Biology: Solid-State NMR Experiments and
Strategies for Understanding the M2 Proton Channel Conductance.
AB - In terms of structural biology, solid-state NMR experiments and strategies have
been well established for resonance assignments, leading to the determination of
three-dimensional structures of insoluble membrane proteins in their native-like
environment. It is also known that NMR has the unique capabilities to
characterize structure-function relationships of membrane-bound biological
systems beyond structural biology. Here, we report on solid-state NMR experiments
and strategies for extracting functional activities on a sub-millisecond time
scale. Specifically, we use the His37-labeled full length M2 (M2FL) protein of
the Influenza A virus embedded in synthetic lipid bilayers as an example to
characterize the proton conduction mechanism and kinetics. The integral membrane
M2 protein assembles as a tetrameric bundle to form a proton-conducting channel
that is activated by low pH and is essential for the viral lifecycle. Our results
present convincing evidence for the formation of imidazolium-imidazole hydrogen
bonds in the His37 tetrad at low pH and that these hydrogen bonds have a low
barrier that facilitates the proton conduction mechanism in the M2FL protein.
Moreover, it has been possible to measure hydronium ion exchange between water
and the protons in the His37 NH bonds based on chemical exchange spectroscopy
with minimized spin diffusion. The results identify an exchange rate constant of
~4000 s-1 for pH 5.8 at -10 degrees C.
PMID- 28425712
TI - Synthesis and Photooxidation of the Trisubstituted Oxazole Fragment of the Marine
Natural Product Salarin C.
AB - The eastern section of the macrocyclic marine natural product salarin C from the
sponge Fascaplysinopsis sp. was synthesized employing a halogen dance reaction to
assemble the trisubstituted oxazole moiety. The synthesis was inspired by
Kashman's hypothesis on the biomimetic oxidation of salarin C to salarin A. Clean
conversion to the triacylamine partial structure of salarin A occurred on
treatment with photochemically generated singlet oxygen. Thus, a Wasserman-type
oxidative rearrangement is chemically possible in this case.
PMID- 28425713
TI - Synthesis of Diverse N-Acryloyl Azetidines and Evaluation of Their Enhanced Thiol
Reactivities.
AB - Acyl azetidines exhibit nonplanar hybridization, leading to lower amide-like
character of the corresponding (O)C-N bonds. This impacts N-acryloyl azetidines
by producing enhanced electrophilicy at appended Michael acceptors. Herein,
reactivity data are reported in the presence of glutathione (GSH) in phosphate
buffer (pH 7.4) at 37 degrees C. Wide reactivity ranges are observed by varying
substitution at the Michael acceptor or by modulating the electron-withdrawing
character of substituents at the C3 position of the azetidine.
PMID- 28425714
TI - Prehydrated One-Electron Attachment to Azido-Modified Pentofuranoses: Aminyl
Radical Formation, Rapid H-Atom Transfer, and Subsequent Ring Opening.
AB - Methyl 2-azido-2-deoxy-alpha-d-lyxofuranoside (1a) and methyl 2-azido-2-deoxy
beta-d-ribofuranoside (2) were prepared from d-xylose or d-arabinose,
respectively. Employing ESR and DFT/B3LYP/6-31G* calculations, we investigated
(i) aminyl radical (RNH.) formation and (ii) reaction pathways of RNH..
Prehydrated electron attachment to 1a and 2 at 77 K produced transient azide
anion radical (RN3.-) which reacts via rapid N2 loss at 77 K, forming nitrene
anion radical (RN.-). Rapid protonation of RN.- at 77 K formed RNH. and -OH. 15N
labeled-1a confirmed this mechanism. Investigations employing in-house
synthesized site-specifically deuterated derivatives of 1a (e.g., CH3 (1b), C4
(1c), and C5 (1d)) established that (a) a facile intramolecular H atom transfer
from C5 to RNH. generated C5. and RNH2. C5. formation had a small deuterium
kinetic isotope effect suggesting that this reaction does not occur via direct H
atom abstraction. (b) Subsequently, C5. underwent a facile unimolecular
conversion to ring-opened C4.. Identification of ring-opened C4. intermediate
confirms the mechanism of C5'. mediated unaltered base release associated with
DNA-strand break. However, for 2, ESR studies established thermally activated
intermolecular H atom abstraction by RNH. from the methyl group at C1. Thus,
sugar ring configuration strongly influences the site and pathway of RNH.
mediated reactions in pentofuranoses.
PMID- 28425715
TI - Five-Fold Ordering in High-Pressure Perovskites RMn3O6 (R = Gd-Tm and Y).
AB - Cation and anion ordering plays an important role in the properties of materials,
in particular, in the properties of perovskite materials. Here we report on
unusual 5-fold cation/charge ordering in high-pressure-synthesized (at 6 GPa and
~1670 K) RMn3O6 perovskites with R = Gd-Tm and Y. R3+, Mn2+, and Mn3+ cations are
ordered at the A site in two separate chains consisting of R3+ and alternating
Mn2+ (in tetrahedral coordination) and Mn3+ (in square-planar coordination),
while Mn3+ and mixed-valent Mn3+/Mn4+ are ordered at the B site in layers. The
ordering can be represented as [R3+Mn2+0.5Mn3+0.5]A[Mn3+Mn3.5+]BO6. The triple
cation ordering observed at the A site is very rare, and the layered double-B
site ordering is also scarce. RMn3O6 compounds crystallize in space group Pmmn
with a = 7.2479(2) A, b = 7.4525(3) A, and c = 7.8022(2) A for DyMn3O6 at 213 K,
and they are structurally related to CaFeTi2O6. They are prone to
nonstoichiometry, R1-deltaMn3O6-1.5delta, where delta = -0.071 to -0.059 for R =
Gd, delta = 0 for R = Dy, delta = 0.05-0.1 for R = Ho and Y, and delta = 0.12 for
R = Er and Tm. They show complex magnetic behaviors with several transition
temperatures, and their magnetic properties are highly sensitive to the delta
values.
PMID- 28425716
TI - Reactions of N2O5 with Salty and Surfactant-Coated Glycerol: Interfacial
Conversion of Br- to Br2 Mediated by Alkylammonium Cations.
AB - Gas-liquid scattering and product-yield experiments are used to investigate
reactions of N2O5 with glycerol containing Br- and surfactant ions. N2O5 oxidizes
Br- to Br2 for every solution tested: 2.7 M NaBr, 0.03 M tetrahexylammonium
bromide (THABr), 0.03 M THABr + 0.5 M NaBr, 0.03 M THABr + 0.5 M NaCl, 0.03 M
THABr + 0.01 M sodium dodecyl sulfate (SDS), and 0.01 M cetyltrimethylammonium
bromide (CTABr). N2O5 also reacts with glycerol itself to produce mono- and
dinitroglycerin. Surface tension measurements indicate that 0.03 M THABr and 2.7
M NaBr have similar interfacial Br- concentrations, though their bulk Br-
concentrations differ by 90-fold. We find that twice as much Br2 is produced in
the presence of THA+, implying that the conversion of Br- to Br2 is initiated at
the interface, perhaps mediated by the charged, hydrophobic pocket within the
surface THA+ cation. The addition of 0.5 M NaBr, 0.5 M NaCl, or 0.01 M SDS to
0.03 M THABr lowers the Br2 production rate by 23%, 63%, and 67% of the THABr
value, respectively. When CTA+ is substituted for THA+, Br2 production drops to
12% of the THABr value. The generation of Br2 under such different conditions
implies that trace amounts of surface-active alkylammonium ions can catalyze
interfacial N2O5 reactions, even when salts and other surfactants are present.
PMID- 28425717
TI - An Experimental and Molecular Dynamics Study of Red Fluorescent Protein mCherry
in Novel Aqueous Amino Acid Ionic Liquids.
AB - The search for biocompatible ionic liquids (ILs) with novel biochemical and
biomedical applications has recently gained greater attention. In this report, we
characterize the effects of two novel amino acid-based aqueous ILs composed of
tetramethylguanidinium (TMG) and amino acids on the structure and stability of a
widely used red fluorescent protein (mCherry). Our experimental data shows that
while the aspartic acid-based IL (TMGAsp) has effects similar to previously
studied conventional ILs (BMIBF4, EMIAc, and TMGAc), the alanine-based IL
(TMGAla) has a much stronger destabilization effect on the protein structure.
Addition of 0.30 M TMGAla to mCherry decreases the unfolding temperature from 83
to 60 degrees C. Even at 25 degrees C, TMGAla results in a blue shift of the
mCherry absorbance and fluorescence peaks and an increased Stokes shift.
Molecular dynamics simulations show that the chromophore conformation and its
interaction with mCherry with TMGAla are changed relative to those with TMGAsp or
in the absence of ILs. Protein-ILs contact analysis indicates that the mCherry
Asp interactions are hydrophilic but the (fewer) mCherry-Ala interactions are
more hydrophobic and may modulate the TMG interaction with the protein. Hence,
the anion hydrophobicity may explain the special TMGAla destabilization of
mCherry.
PMID- 28425718
TI - Testing High Concentrations of Membrane Active Antibiotic Chlorhexidine Via
Computational Titration and Calorimetry.
AB - Coarse-grained strategies for membrane simulations are designed to increase
efficiency for larger and more complex molecular dynamics simulations. For
membrane active antibiotics, the concentration dependence of their action
presents a tremendous challenge in simulation scale. In this study, we examine
the effects of concentration for the popular membrane active antibacterial drug
chlorhexidine. It presents an interesting biophysical modeling test, where from
experimental experience we know that model membranes of 1,2-dimyristoyl-sn
glycero-3-phosphocholine (DMPC) can absorb very high quantities of the drug
without disruption. We construct a coarse-grained model of chlorhexidine in three
different charged states and compare to previous all-atom simulations and new
experiments. Using large, long-time, and unbiased simulations of chlorhexidine
inserting into the lipid bilayer, we find little changes to the functional
structure of a DMPC membrane up through concentrations of 15:100 drug:lipid,
where the slowing rate of continued insertion tests the capabilities of even this
coarse-grained approach. We validate our simulations with computational
calorimetry measurements, and show that they agree with new experimental data
from differential scanning calorimetry.
PMID- 28425719
TI - Adsorption of Nitrate and Bicarbonate on Fe-(Hydr)oxide.
AB - In this work, we used density functional theory calculations to study the
resulting complexes of adsorption and of inner- and outer-sphere adsorption-like
of bicarbonate and nitrate over Fe-(hydr)oxide surfaces using acidic, neutral,
and basic simulated pH conditions. High-spin states that follow the 5N + 1 (N is
the number of Fe atoms, each having five unpaired electrons) rule are preferred.
Monodentate mononuclear (MM1) surface complexes are shown to lead to the most
favorable thermodynamic adsorption for both bicarbonate and nitrate with -63.91
and -28.25 kJ/mol, respectively, under neutral conditions. Our results suggest
that four types of regular and charged-assisted hydrogen bonds are involved in
the adsorption process; all of them can be classified as closed-shell (long-range
or ionic). The formal charges induce unusually short and strong hydrogen bonds.
The ability of high multiplicity states of Fe clusters to adsorb oxyanions in
solvated environments arises from orbital interactions: the 4s virtual orbitals
in Fe have a large affinity for the 2p-type electron pairs of oxygens.
PMID- 28425720
TI - A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos.
AB - The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing
the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to
cause their ubiquitination and degradation. Here we describe CC-220 (compound 6),
a cereblon modulator in clinical development for systemic lupus erythematosis and
relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher
affinity than lenalidomide or pomalidomide. Consistent with this, the cellular
degradation of Ikaros and Aiolos is more potent and the extent of substrate
depletion is greater. The crystal structure of cereblon in complex with DDB1 and
compound 6 reveals that the increase in potency correlates with increased
contacts between compound 6 and cereblon away from the modeled binding site for
Ikaros/Aiolos. These results describe a new cereblon modulator which achieves
greater substrate degradation via tighter binding to the cereblon E3 ligase and
provides an example of the effect of E3 ligase binding affinity with relevance to
other drug discovery efforts in targeted protein degradation.
PMID- 28425721
TI - Co(III)-Catalyzed Enaminone-Directed C-H Amidation for Quinolone Synthesis.
AB - We report herein the development of a Co(III)-catalyzed enaminone-directed C-H
amidation method for synthetic access to quinolones, an important heterocyclic
scaffold for diverse pharmaceutically active structures. The C-H coupling with
dioxazolones and subsequent deacylation of an installed amide group allow
consecutive C-N coupling generation of quinolones with wide-ranging compatible
substituent patterns.
PMID- 28425722
TI - Giant Electrostrictive Response and Piezoresistivity of Emulsion Templated
Nanocomposites.
AB - Using an emulsion road and optimizing the dispersion process, we prepare polymer
carbone nanotubes (CNT) and polymer reduced graphene oxide (rGO) composites. The
introduction of conductive nanoparticles into polymer matrices modifies the
electronic properties of the material. We show that these materials exhibit giant
electrostriction coefficients in the intermediate filler concentration (below 1
wt %). This makes them very promising for applications such as capacitive sensors
and actuators. In addition, the values of the piezoresistivity measured in the
high filler concentration situation are at least an order of magnitude greater
than the one reported in the literature. This opens the way to use these
materials for stress or strain sensor applications considering their giant
responses to mechanical deformations.
PMID- 28425723
TI - Decreases in implicit self-esteem explain the racial impact of microaggressions
among Asian Americans.
AB - Asian Americans are commonly perceived as perpetual foreigners and, therefore,
not "true" Americans. Asian Americans report inquiries about nationality and
English abilities as the most common forms of racial microaggressions perpetrated
by White Americans (Sue, 2015). Race theorists assert that these microaggressions
are race-related and marginalize Asian Americans. Scholars have claimed that
these subtle acts are harmful, yet only a few studies have uncovered the
mechanisms by which racial microaggressions affect mental and physical well-being
(Ong, Burrow, Fuller-Rowell, Ja, & Sue, 2013; Wong, Derthick, David, Saw, &
Okazaki, 2013). The current study conceptualized racial microaggressions as a
stressor to address the major gaps in research. Specifically, this study (a)
experimentally tested the race-related nature of the microaggression event to
determine whether a White American perpetrator would elicit more stress in Asian
Americans compared to an Asian American perpetrator and (b) examined threats to
explicit and implicit self-esteem as possible mediators of microaggression
generated stress. Findings confirmed that the race of the perpetrator did have an
impact on stress among Asian Americans. In the multiple meditation analysis,
experience with a White American perpetrator, compared to an Asian American
perpetrator, lowered implicit self-esteem, which resulted in more stress.
Implications and strategies for counseling Asian American clients are discussed.
(PsycINFO Database Record
PMID- 28425724
TI - Factors impacting sense of community among adults with brain injury.
AB - PURPOSE: Despite increasing interest in examining community outcomes following
disability, sense of community (SOC) has received relatively no attention in the
rehabilitation literature. SOC refers to feelings of belonging and attachment one
has for a community and is of particular relevance for people with brain injury
who are at increased risk of social isolation. The aim of this study was to
investigate factors contributing to SOC for individuals with brain injury.
METHOD: Members from 2 brain injury associations (n = 98) participated in this
survey-based study. Hierarchical regression analysis was used to explore
demographic, disability-related, community and social participation variables'
impact on SOC with regard to one's town or city. Follow-up mediation analyses
were conducted to explore relationships among social self-efficacy, support
network, neighboring behavior, and SOC. RESULTS: Findings indicated that
disability-related and community variables accounted for over 40% of the variance
in SOC. Size of social support network was the only significant independent
contributor to SOC variance. Follow-up analyses provided support for (a) the
partial mediating effect of social support network size on the relationship
between social self-efficacy and SOC, and (b) the mediating effect of neighboring
behavior on the relationship between social self-efficacy and social support
network size. CONCLUSIONS: Findings from this study highlight the particular
importance of self-efficacy, social support, and neighboring behaviors in
promoting SOC for people with brain injury. Recommendations are provided to
advance research efforts and inform intervention approaches to improve the felt
experience of community among people with brain injury. (PsycINFO Database Record
PMID- 28425725
TI - "Defining 'peerness' in peer-delivered health and wellness interventions for
serious mental illness": Correction to Muralidharan et al. (2017).
AB - Reports an error in "Defining "peerness" in peer-delivered health and wellness
interventions for serious mental illness": Response to letter to the editor" by
Jody Silver and Patricia B. Nemec (Psychiatric Rehabilitation Journal, 2017[Mar],
Vol 40[1], 116). The article was mislabeled as Editorial and should be a Comment.
The Response to Letter to the Editor section should be a Reply and now has its
own http://dx.doi.org/10.1037/ h0101580. (The following abstract of the original
article appeared in record 2017-13876-001.) Replies to comments by Muralidharan
et al (see record 2017-13255-009) on the original article by Silver and Nemec
(see record 2016-43088-001). The original authors thank the commentators for
raising additional questions regarding "peerness." They were honored that their
paper prompted this thought and effort to submit comments. (PsycINFO Database
Record
PMID- 28425726
TI - Comparisons between the Minnesota Multiphasic Personality Inventory-Adolescent
Restructured Form (MMPI-A RF) and MMPI-A in adolescent psychiatric inpatients.
AB - This study explored the association between the Minnesota Multiphasic Personality
Inventory (MMPI)-Adolescent-Restructured Form (MMPI-A-RF) and the MMPI-Adolescent
(MMPI-A) form in a sample of 3,516 adolescents receiving inpatient psychiatric
treatment, including 2,798 adolescents meeting validity inclusion cutoffs for
both measures. There was 92.5% agreement rate with respect to global
identification of cases as valid or invalid and some empirical support for
lowering interpretive cutoffs for validity scales on the MMPI-A-RF. The MMPI-A-RF
Demoralization Scale (RCd) was shown to correlate significantly less strongly
with Restructured Clinical (RC) scales than with MMPI-A clinical scales. RC
scales also demonstrated significantly lower mean interscale correlations than
MMPI-A clinical scales. As expected, this greater level of scale independence
resulted in significantly fewer profiles with multiple scale elevations. As was
anticipated, with the exception of RC1 predicting MMPI-A hypochondriasis,
correlational and classification agreement analyses suggested moderate
associations between the RC and MMPI-A clinical scales, but somewhat stronger
agreement between comparable PSY-5 scales. Changes in interpretive cutoff
procedures for the RC scales, including RCd, also resulted in 5.5% fewer "within
normal limits" profiles than the use of MMPI-A with all 10 clinical scales.
Finally, stepwise linear regression analyses indicated that MMPI-A-RF Higher
Order scales were best predicted by those MMPI-A clinical scale combinations that
they are purported to be linked with in the MMPI-A-RF manual. (PsycINFO Database
Record
PMID- 28425727
TI - Longitudinal associations of neighborhood collective efficacy and maternal
corporal punishment with behavior problems in early childhood.
AB - Neighborhood and parenting influences on early behavioral outcomes are strongly
dependent upon a child's stage of development. However, little research has
jointly considered the longitudinal associations of neighborhood and parenting
processes with behavior problems in early childhood. To address this limitation,
this study explores the associations of neighborhood collective efficacy and
maternal corporal punishment with the longitudinal patterns of early
externalizing and internalizing behavior problems. The study sample consisted of
3,705 families from a nationally representative cohort study of urban families.
Longitudinal multilevel models examined the associations of collective efficacy
and corporal punishment with behavior problems at age 3, as well as with patterns
of behavior problems between the ages 3 to 5. Interactions between the main
predictors and child age tested whether neighborhood and parent relationships
with child behavior varied over time. Mediation analysis examined whether
neighborhood influences on child behavior were mediated by parenting. The models
controlled for a comprehensive set of possible confounders at the child, parent,
and neighborhood levels. Results indicate that both maternal corporal punishment
and low neighborhood collective efficacy were significantly associated with
increased behavior problems. The significant interaction between collective
efficacy and child age with internalizing problems suggests that neighborhood
influences on internalizing behavior were stronger for younger children. The
indirect effect of low collective efficacy on behavior problems through corporal
punishment was not significant. These findings highlight the importance of
multilevel interventions that promote both neighborhood collective efficacy and
nonphysical discipline in early childhood. (PsycINFO Database Record
PMID- 28425728
TI - Parent- and teacher-child relationships and engagement at school entry:
Mediating, interactive, and transactional associations across contexts.
AB - Early school engagement patterns set the stage for short- and long-term academic
behaviors and progress, and low engagement at school entry can give rise to
dysfunctional school behavior and underachievement in later years. Relationships
with parents and teachers provide a foundation upon which children develop the
skills and behaviors that are critical for engagement in early elementary school.
However, the cross-contextual and transactional processes by which these
relationships are associated with engagement in early elementary school remain
unclear. This investigation therefore considers how children's relationships with
parents prior to school entry are indirectly and interactively associated with
1st grade engagement through teacher-child relationships. It also considers how
early cognitive, self-regulatory, and behavioral skills and competencies elicit
these relational responses. This investigation drew upon multimethod data from
triangulated sources (parents, teachers, and direct observation) available within
a large longitudinal study, the National Institute of Child Health and Human
Development Study of Early Child Care and Youth Development. Results indicate
that neither 54-month or 1st grade parent-child relationships were directly
associated with children's engagement in early elementary school. However, 1st
grade teacher conflict was problematic for children's developing engagement. In
turn, teacher conflict partially mediated linkages between maternal sensitivity
and conflict prior to school entry and engagement in 1st grade. Parental
closeness and sensitivity also buffered children against negative associations
between teacher conflict and engagement. Finally, children's early skills and
competencies at 36 months elicited relational processes that were indirectly
associated with engagement. Conceptual, theoretical, and methodological
challenges are also discussed. (PsycINFO Database Record
PMID- 28425729
TI - Some properties of p-curves, with an application to gradual publication bias.
AB - p-curves provide a useful window for peeking into the file drawer in a way that
might reveal p-hacking (Simonsohn, Nelson, & Simmons, 2014a). The properties of p
curves are commonly investigated by computer simulations. On the basis of these
simulations, it has been proposed that the skewness of this curve can be used as
a diagnostic tool to decide whether the significant p values within a certain
domain of research suggest the presence of p-hacking or actually demonstrate that
there is a true effect. Here we introduce a rigorous mathematical approach that
allows the properties of p-curves to be examined without simulations. This
approach allows the computation of a p-curve for any statistic whose sampling
distribution is known and thereby allows a thorough evaluation of its properties.
For example, it shows under which conditions p-curves would exhibit the shape of
a monotone decreasing function. In addition, we used weighted distribution
functions to analyze how 2 different types of publication bias (i.e., cliff
effects and gradual publication bias) influence the shapes of p-curves. The
results of 2 survey experiments with more than 1,000 participants support the
existence of a cliff effect at p = .05 and also suggest that researchers tend to
be more likely to recommend submission of an article as the level of statistical
significance increases beyond this p level. This gradual bias produces right
skewed p-curves mimicking the existence of real effects even when no such effects
are actually present. (PsycINFO Database Record
PMID- 28425731
TI - Changes in perception-action tuning over long time scales: How children and
adults perceive and act on dynamic affordances when crossing roads.
AB - This investigation examined developmental change in how children perceive and act
on dynamic affordances when crossing roads on foot. Six- to 14-year-olds and
adults crossed roads with continuous cross-traffic in a large-screen, immersive
pedestrian simulator. We observed change both in children's gap choices and in
their ability to precisely synchronize their movement with the opening of a gap.
Younger children were less discriminating than older children and adults,
choosing fewer large gaps and more small gaps. Interestingly, 12-year-olds' gap
choices were significantly more conservative than those of 6-, 8-, 10-, and 14
year-olds, and adults. Timing of entry behind the lead vehicle in the gap (a key
measure of movement coordination) improved steadily with development, reaching
adultlike levels by age 14. Coupled with their poorer timing of entry, 6-, 8-,
and 10-year-olds' gap choices resulted in significantly less time to spare and
more collisions than 14-year-olds and adults. Time to spare did not differ
between 12-year-olds, 14-year-olds, and adults, indicating that 12-year-olds'
more conservative gap choices compensated for their poorer timing of entry. The
findings show that children's ability to perceive and act on dynamic affordances
undergoes a prolonged period of development, and that older children appear to
compensate for their poorer movement timing skills by adjusting their gap
decisions to match their crossing actions. Implications for the development of
perception-action tuning and road-crossing skills are discussed. (PsycINFO
Database Record
PMID- 28425730
TI - The relation of anxiety and cognition in Parkinson's disease.
AB - OBJECTIVE: Parkinson's disease (PD) has long been conceptualized as a motor
disorder, but nonmotor symptoms also manifest in the disease and significantly
reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor
symptoms, even in early disease stages, but the relation between these symptoms
remains poorly understood. We examined self-reported anxiety and neurocognitive
function, indexed by measures of executive function (set-shifting and phonemic
fluency), categorical fluency, and attention/working memory. We hypothesized that
anxiety would correlate with cognitive performance. METHOD: The Beck Anxiety
Inventory and cognitive tests (Trail Making, Verbal Fluency, Digit Span) were
administered to 77 nondemented adults with mild to moderate idiopathic PD (39
men, 38 women; Mage = 62.9 years). RESULTS: Higher anxiety was associated with
more advanced disease stage and severity and with poorer set-shifting when using
a derived metric to account for motoric slowing. Depression correlated with
greater anxiety and disease severity, but not with cognitive performance.
CONCLUSIONS: Our findings support the association of anxiety with a specific
domain of executive function, set-shifting, in nondemented individuals with mild
to moderate PD, raising the possibility that treatment of anxiety may alleviate
aspects of executive dysfunction in this population. (PsycINFO Database Record
PMID- 28425732
TI - Distractor probability changes the shape of the attentional template.
AB - Theories of attention commonly refer to the "attentional template" as the
collection of features in working memory that represent the target of visual
search. Many models of attention assume that the template contains a veridical
representation of target features, but recent studies have shown that the target
representation is "shifted" away from distractor features in order to optimize
their distinctiveness and facilitate visual search. Here, we manipulated the
probability of target-similar distractors during a visual search task in 2
groups, and separately measured the contents of the attentional template. We
hypothesized that having a high probability of target-similar distractors would
increase pressure to shift and/or sharpen the target representation in order to
increase the distinctiveness of targets from distractors. We found that the high
similarity group experienced less distractor interference during visual search,
but only for highly target-similar distractors. Additionally, while both groups
shifted the target representation away from the actual target color, the high
similarity group also had a sharper representation of the target color. We
conclude that the contents of the attentional template in working memory can be
flexibly adjusted with multiple mechanisms to increase target-to-distractor
distinctiveness and optimize attentional selection. (PsycINFO Database Record
PMID- 28425733
TI - Contingent capture is weakened in search for multiple features from different
dimensions.
AB - Can observers maintain more than 1 attentional set and search for 2 features in
parallel? Previous studies that relied on attentional capture by irrelevant
distractors to answer this question focused on features from the same dimension
and specifically, on color. They showed that 2 separate color templates can guide
attention selectively and simultaneously. Here, the authors investigated
attentional guidance by 2 features from different dimensions. In three spatial
cueing experiments, they compared contingent capture during single-set versus
dual-set search. The results showed that attention was guided less efficiently by
2 features than by just 1. This impairment varied considerably across target
feature dimensions (color, size, shape and orientation). Confronted with previous
studies, our findings suggest avenues for future research to determine whether
impaired attentional guidance by multiple templates occurs only in cross
dimensional disjunctive search or also in within-dimension search. The present
findings also showed that although performance improved when the target feature
repeated on successive trials, a relevant-feature cue did not capture attention
to a larger extent when its feature matched that of the previous target. These
findings suggest that selection history cannot account for contingent capture and
affects processes subsequent to target selection. (PsycINFO Database Record
PMID- 28425734
TI - A within-person approach to risk for suicidal ideation and suicidal behavior:
Examining the roles of depression, stress, and abuse exposure.
AB - OBJECTIVE: This study tests a novel, within-person model that reexamines
depression and stress as risk factors for suicidal ideation and behavior among
adolescent girls with and without sexual/physical abuse histories. METHOD: This
longitudinal study includes data from 220 adolescent girls between 12 and 16
years of age (M = 14.69 years, SD = 1.37; 61% White). At baseline, adolescents
reported the presence or absence of prior abuse as part of a clinical interview.
At baseline and every 3 months for 18 months, adolescents completed measures of
suicidal ideation and behavior, depressive symptoms, and stress. RESULTS:
Multilevel models examined within-person mean, deviations from within-person
mean, depression, and stress and their interactions with abuse as predictors of
suicidal ideation and behavior. In addition to within-person mean depression,
higher-than-usual depression (odds ratio [OR] = 1.99) and higher-than-usual
stress (OR = 1.53) predicted greater risk of suicidal ideation at each follow-up
assessment. Periods of higher-than-usual stress (1 SD increase) and periods of
higher-than-usual depression (1 SD increase) were associated with an 82% and 57%
increase in the odds of suicidal behavior, respectively, but only among those
with abuse histories. CONCLUSION: Depression, stress, and abuse are well-known
risk factors for suicidal ideation and behavior; however, it has been unclear for
whom, and when, these factors have their greatest impact. These results show that
depression and stress are potent risk factors among those with a history of abuse
and that within-person elevations in these risk factors signal increased short
term risk of suicidal ideation and behavior. (PsycINFO Database Record
PMID- 28425735
TI - Clinician-led, peer-led, and internet-delivered dissonance-based eating disorder
prevention programs: Acute effectiveness of these delivery modalities.
AB - OBJECTIVE: Because independent trials have provided evidence for the efficacy and
effectiveness of the dissonance-based Body Project eating disorder prevention
program, the present trial tested whether clinicians produce the largest
intervention effects, or whether delivery can be task-shifted to less expensive
undergraduate peer educators or to Internet delivery without effect size
attenuation, focusing on acute effects. METHOD: In this study, 680 young women
(Mage = 22.2 years, SD = 7.1) recruited at colleges in 2 states were randomized
to clinician-led Body Project groups, peer-led Body Project groups, the Internet
based eBody Project, or an educational video control condition. RESULTS:
Participants in all 3 variants of the Body Project intervention showed
significantly greater reductions in eating disorder risk factors and symptoms
than did educational video controls. Participants in clinician-led and peer-led
Body Project groups showed significantly greater reductions in risk factors than
did eBody Project participants, but effects for the 2 types of groups were
similar. Eating disorder onset over 7-month follow-up was significantly lower for
peer-led Body Project group participants versus eBody Project participants (2.2%
vs. 8.4%) but did not differ significantly between other conditions. CONCLUSIONS:
The evidence that all 3 dissonance-based prevention programs outperformed an
educational video condition, that both group-based interventions outperformed the
Internet-based intervention in risk factor reductions, and that the peer-led
groups showed lower eating disorder onset over follow-up than did the Internet
based intervention is novel. These acute-effects data suggest that both group
based interventions produce superior eating disorder prevention effects than does
the Internet-based intervention and that delivery can be task-shifted to peer
leaders. (PsycINFO Database Record
PMID- 28425736
TI - Implicit approach and avoidance in patients with obsessive-compulsive disorder.
AB - Avoidance is regarded as an important feature for the development and maintenance
of obsessive-compulsive disorder (OCD) and is usually assessed using explicit
measures such as self-report scales. However, some behavioral schemata are
unavailable to introspection, making them partially inaccessible by explicit
measures. We used an approach-avoidance task (AAT) as an implicit measure to
examine behavioral tendencies in patients with OCD, including patients with
checking- and contamination-related symptoms (n = 63), compared with a healthy
control group (n = 30). Participants were asked to respond to the color of a
stimulus or stimulus frame by pulling a joystick toward themselves or by pushing
it away. The stimuli were comprised of checking-related, contamination-related,
and neutral pictures and words. Patients with contamination-related symptoms were
slower when responding to OCD-related stimuli, independent of approach or
avoidance. Unexpectedly, patients with checking-related symptoms were faster at
pulling (approaching) and slower at pushing (avoiding) checking-related material
compared with neutral stimuli. The slower pushing (avoiding) of checking-related
compared with neutral material correlated positively with explicit ratings of
avoidance. These results suggest a biased approach-avoidance tendency in patients
with checking-related symptoms of OCD, but not in those with contamination
related symptoms of OCD. Future studies are necessary to assess whether the AAT
might be useful in the assessment of treatment gains as well as whether it might
be a training tool to enhance psychotherapeutic changes in OCD. (PsycINFO
Database Record
PMID- 28425738
TI - The link between discrimination and telomere length in African American adults.
AB - OBJECTIVE: Prior work shows that discrimination is associated with a wide array
of negative health outcomes. However, the biological mechanisms through which
this link occurs require more study. We evaluated the association between
discrimination and leukocyte telomere length (LTL; a biological marker of
systemic aging). METHOD: Cross-sectional data were from the Health and Retirement
study, a study of people aged 51+ in the United States, and included 595 African
American males and females. Multiple regression analyses were used to evaluate
whether discrimination was independently associated with LTL. We also considered
the role of potential confounders including sociodemographic factors, health
factors, depressive symptoms, and stress. RESULTS: High discrimination was
associated with shorter LTL after controlling for sociodemographic factors (b =
.034, SE = 0.14, p = .017). This association persisted in analyses that further
adjusted for health factors, depressive symptoms, and stress. CONCLUSION: Results
suggest that discrimination experiences accelerate biological aging in older
African American males and females, alike. This finding helps advance our
understanding of how discrimination generates greater disease vulnerability and
premature death in African Americans. (PsycINFO Database Record
PMID- 28425737
TI - Time-varying and time-invariant dimensions of depression in children and
adolescents: Implications for cross-informant agreement.
AB - The longitudinal structure of depression in children and adolescents was examined
by applying a Trait-State-Occasion structural equation model to 4 waves of self,
teacher, peer, and parent reports in 2 age groups (9 to 13 and 13 to 16 years
old). Analyses revealed that the depression latent variable consisted of 2
longitudinal factors: a time-invariant dimension that was completely stable over
time and a time-varying dimension that was not perfectly stable over time.
Different sources of information were differentially sensitive to these 2
dimensions. Among adolescents, self- and parent reports better reflected the time
invariant aspects. For children and adolescents, peer and teacher reports better
reflected the time-varying aspects. Relatively high cross-informant agreement
emerged for the time-invariant dimension in both children and adolescents. Cross
informant agreement for the time-varying dimension was high for adolescents but
very low for children. Implications emerge for theoretical models of depression
and for its measurement, especially when attempting to predict changes in
depression in the context of longitudinal studies. (PsycINFO Database Record
PMID- 28425740
TI - "Healthier than thou? 'Practicing what you preach' backfires by increasing
anticipated devaluation": Correction to Howe and Monin (2017).
AB - Reports an error in "Healthier Than Thou? "Practicing What You Preach" Backfires
by Increasing Anticipated Devaluation" by Lauren C. Howe and Benoit Monin
(Journal of Personality and Social Psychology, Advanced Online Publication, Feb
27, 2017, np). In the article, the beginning phrase of the second paragraph of
the Internal Meta-Analysis of Studies 3 Through 5 section is incorrect. It should
instead begin as follows: Across the three studies. The Monin et al. (2014)
reference in both the References list and in text is included in error. The
correct citation should read as follows: Monin, B., & Oppenheimer, D. M. (2014).
The limits of direct replications and the virtues of stimulus sampling:
Commentary on Klein et al., 2014. Social Psychology, 45, 299-300. (The following
abstract of the original article appeared in record 2017-08697-001.) Should
experts always practice what they preach? When an expert displays exemplary
behavior, individuals who fear negative devaluation sometimes anticipate that
this expert will look down on them. As a result, displays of excellence can
paradoxically turn off the very people they are trying to inspire. Five studies
document this in the medical domain, showing that individuals who are overweight
or obese and concerned about their weight avoid physicians who advertise their
fitness, for fear that these doctors will judge them negatively. People
(erroneously) believe that doctors have healthier habits than other individuals
(Study 1), doctors advertise healthy habits (Study 2), and overweight individuals
anticipate devaluation from, and thus avoid and feel less comfortable with,
doctors who portray themselves as fitness-focused (Study 3). Studies 4 and 5 test
strategies for physicians to emphasize their own fitness without turning off
weight-sensitive patients. This work demonstrates that it is critical to take
into account ego-defensive processes when attempting to lead by example.
(PsycINFO Database Record
PMID- 28425739
TI - Sleep duration partially accounts for race differences in diurnal cortisol
dynamics.
AB - OBJECTIVE: Emerging research demonstrates race differences in diurnal cortisol
slope, an indicator of hypothalamic-pituitary-adrenocortical (HPA)-axis
functioning associated with morbidity and mortality, with African Americans
showing flatter diurnal slopes than their White counterparts. Sleep
characteristics are associated with both race and with HPA-axis functioning. The
present report examines whether sleep duration may account for race differences
in cortisol dynamics. METHOD: Participants were 424 employed African American and
White adults (mean age = 42.8 years, 84.2% White, 53.6% female) with no
cardiovascular disease (Adult Health and Behavior Project-Phase 2 [AHAB-II]
cohort, University of Pittsburgh). Cortisol slope was calculated using 4 salivary
cortisol readings, averaged over each of 4 days. Demographic (age, sex),
psychosocial (socioeconomic status [SES], affect, discrimination), and health
behaviors (smoking, alcohol use, physical activity) variables were used as
covariates, and sleep (self-report and accelerometry) was also assessed. RESULTS:
African Americans had flatter slopes than Whites (F(1, 411) = 10.45, B = .02, p =
.001) in models adjusting for demographic, psychosocial, and health behavior
covariates. Shorter actigraphy-assessed total sleep time was a second significant
predictor of flatter cortisol slopes (F(1, 411) = 25.27, B = -.0002, p < .0001).
Total sleep time partially accounted for the relationship between race and
diurnal slope [confidence interval = .05 (lower = .014, upper .04)]. CONCLUSIONS:
African Americans have flatter diurnal cortisol slopes than their White
counterparts, an effect that may be partially attributable to race differences in
nightly sleep duration. Sleep parameters should be considered in further research
on race and cortisol. (PsycINFO Database Record
PMID- 28425741
TI - Development of identity clarity and content in adulthood.
AB - The current research examines self-concept clarity over 2 assessment points with
the aims of establishing patterns of stability and change in self-concept clarity
across adulthood, modeling corollary changes in traits and health-related role
limitations, and demonstrating the ways in which gender and age moderate these
patterns. Within this sample of 461 adults age 19-86 years of age, self-concept
clarity had robust rank-order stability and no significant mean-level change
during a 3-year assessment window. However, significant interindividual
variability was present in the developmental patterns of self-concept clarity
over time. These individual differences in development of self-concept clarity
corresponded to developmental patterns in Big Five personality traits and health
related role limitations. Results of this 2 wave longitudinal study suggest 3
primary conclusions: (a) self-concept clarity predicts and corresponds to trait
maturation over time, (b) decreasing self-concept clarity corresponds to
increasing role limitations, and (c) these effects are somewhat contingent on
gender and age. Results are discussed in reference to the maturation of identity
content and metacognitive identity evaluation over the life span. (PsycINFO
Database Record
PMID- 28425743
TI - I'm not the person I used to be: The self and autobiographical memories of
immoral actions.
AB - People maintain a positive identity in at least two ways: They evaluate
themselves more favorably than other people, and they judge themselves to be
better now than they were in the past. Both strategies rely on autobiographical
memories. The authors investigate the role of autobiographical memories of lying
and emotional harm in maintaining a positive identity. For memories of lying to
or emotionally harming others, participants judge their own actions as less
morally wrong and less negative than those in which other people lied to or
emotionally harmed them. Furthermore, people judge those actions that happened
further in the past to be more morally wrong than those that happened more
recently. Finally, for periods of the past when they believed that they were very
different people than they are now, participants judge their actions to be more
morally wrong and more negative than those actions from periods of their pasts
when they believed that they were very similar to who they are now. The authors
discuss these findings in relation to theories about the function of
autobiographical memory and moral cognition in constructing and perceiving the
self over time. (PsycINFO Database Record
PMID- 28425742
TI - Comparing and validating methods of reading instruction using behavioural and
neural findings in an artificial orthography.
AB - There is strong scientific consensus that emphasizing print-to-sound
relationships is critical when learning to read alphabetic languages.
Nevertheless, reading instruction varies across English-speaking countries, from
intensive phonic training to multicuing environments that teach sound- and
meaning-based strategies. We sought to understand the behavioral and neural
consequences of these differences in relative emphasis. We taught 24 English
speaking adults to read 2 sets of 24 novel words (e.g., /buv/, /sig/), written in
2 different unfamiliar orthographies. Following pretraining on oral vocabulary,
participants learned to read the novel words over 8 days. Training in 1 language
was biased toward print-to-sound mappings while training in the other language
was biased toward print-to-meaning mappings. Results showed striking benefits of
print-sound training on reading aloud, generalization, and comprehension of
single words. Univariate analyses of fMRI data collected at the end of training
showed that print-meaning relative to print-sound relative training increased
neural effort in dorsal pathway regions involved in reading aloud. Conversely,
activity in ventral pathway brain regions involved in reading comprehension was
no different following print-meaning versus print-sound training. Multivariate
analyses validated our artificial language approach, showing high similarity
between the spatial distribution of fMRI activity during artificial and English
word reading. Our results suggest that early literacy education should focus on
the systematicities present in print-to-sound relationships in alphabetic
languages, rather than teaching meaning-based strategies, in order to enhance
both reading aloud and comprehension of written words. (PsycINFO Database Record
PMID- 28425744
TI - Once a frog-lover, always a frog-lover?: Infants' goal generalization is
influenced by the nature of accompanying speech.
AB - The ability to interpret choices as enduring preferences that generalize beyond
the immediate situation gives adults a powerful means of predicting and
explaining others' behavior. How do infants come to recognize that current
choices can be driven by generalizable preferences? Although infants can encode
others' actions in terms of goals (Woodward, 1998), there is evidence that 10
month-olds still fail to generalize goal information presented in one environment
to an event sequence occurring in a new environment (Sommerville & Crane, 2009).
Are there some circumstances in which infants interpret others' goals as
generalizable across environments? We investigate whether the vocalizations a
person produces while selecting an object in one room influences infants'
generalization of the goal to a new room. Ten-month-olds did not spontaneously
generalize the actor's goal, but did generalize the actor's goal when the actor
initially accompanied her object selection with a statement of preference.
Infants' generalization was not driven by the attention-grabbing features of the
statement or the mere use of language, as they did not generalize when the actor
used matched nonspeech vocalizations or sung speech. Infants interpreted the goal
as person-specific, as they did not generalize the choice to a new actor. We
suggest that the referential specificity of accompanying speech vocalizations
influences infants' tendency to interpret a choice as personal rather than
situational. (PsycINFO Database Record
PMID- 28425745
TI - When good is stickier than bad: Understanding gain/loss asymmetries in sequential
framing effects.
AB - Considerable research has demonstrated the power of the current positive or
negative frame to shape people's current judgments. But humans must often learn
about positive and negative information as they encounter that information
sequentially over time. It is therefore crucial to consider the potential
importance of sequencing when developing an understanding of how humans think
about valenced information. Indeed, recent work looking at sequentially
encountered frames suggests that some frames can linger outside the context in
which they are first encountered, sticking in the mind so that subsequent frames
have a muted effect. The present research builds a comprehensive account of
sequential framing effects in both the loss and the gain domains. After seeing
information about a potential gain or loss framed in positive terms or negative
terms, participants saw the same issue reframed in the opposing way. Across 5
studies and 1566 participants, we find accumulating evidence for the notion that
in the gain domain, positive frames are stickier than negative frames for novel
but not familiar scenarios, whereas in the loss domain, negative frames are
always stickier than positive frames. Integrating regulatory focus theory with
the literatures on negativity dominance and positivity offset, we develop a new
and comprehensive account of sequential framing effects that emphasizes the
adaptive value of positivity and negativity biases in specific contexts. Our
findings highlight the fact that research conducted solely in the loss domain
risks painting an incomplete and oversimplified picture of human bias and suggest
new directions for future research. (PsycINFO Database Record
PMID- 28425746
TI - Look on the bright side: Positivity bias modulates interference effects in the
simon task.
AB - Negative faces are detected more quickly but categorized more slowly than
positive faces. Using a Simon task, we examined stimulus- and response-related
processes of this dissociation: If negative stimuli are both processed and
responded to more quickly than positive ones, they should elicit reduced Simon
effects. Conversely, if negative stimuli are processed more quickly but responded
to more slowly, enlarged Simon effects should occur. Consistent with the first
possibility, negative stimuli showed reduced Simon effects. Unexpectedly, this
reduction transferred to neutral stimuli (arrows and pointing hands) requiring
the same response as negative faces. This pattern suggests that spatial attention
became biased toward the side associated with a positive-face response and away
from the side associated with a negative-face response, demonstrating that,
similar to higher level cognitive decision processes, even early attentional
processes can be subject to a positivity bias ("Pollyanna effect"). (PsycINFO
Database Record
PMID- 28425747
TI - Early change in coping strategies in responsive treatments for borderline
personality disorder: A mediation analysis.
AB - BACKGROUND: Difficulty in emotion regulation is a hallmark feature of patients
with borderline personality disorder (BPD). Therefore, change in the frequency of
certain patients' coping strategies-aiming at emotion regulation-are among the
most promising mechanisms of change in treatments for BPD. In parallel, it was
highlighted that therapist responsiveness significantly contributed to outcome
across treatment approaches (Stiles, 2009). Based on a randomized controlled
trial (Kramer et al., 2014), the present process-outcome mediation analysis aims
at examining the patient's early change in frequency of coping strategies-in
particular the decrease in behavioral forms of coping-as potential mechanism of
change in responsive treatments for BPD. METHOD: A total of 57 patients with BPD
were included in the present analysis, out of whom 27 were randomly assigned to a
10-session psychiatric treatment and 30 to a 10-session psychiatric treatment
augmented with the responsive intervention of the motive-oriented therapeutic
relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were
transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et
al., 2005; 171 sessions analyzed in total), a validated observer-rated method for
assessing coping strategies in the therapy process. Psychological distress was
assessed using the OQ-45 at intake, after Session 5, and after Session 10.
RESULTS: The results confirmed a responsiveness effect associated with the motive
oriented therapeutic relationship and showed a significant decrease in frequency
of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not
different between the 2 conditions. In addition, we demonstrated that the early
decrease in behavioral forms of coping between Sessions 1 and 5 partially
mediated the link between the group assignment and the change in psychological
distress between Sessions 5 and 10. CONCLUSIONS: These results shed light on the
centrality of therapist responsiveness in treatments for BPD and its impact on
very early change in patient's in-session behavioral coping strategies,
contributing to the effectiveness of short-term treatments for BPD. (PsycINFO
Database Record
PMID- 28425748
TI - A field analysis trial comparing the turnaround times of routine and STAT red
blood cell immunohematology testing.
AB - CONCLUSIONS: The turnaround time (TAT) for pre-transfusion testing is important
for prompt clinical decision-making. TAT includes the time between the arrival of
the sample and the initiation of testing, plus the processing time (PT) required
to generate and report a result. The TAT in larger blood banks is mostly
dependent upon the capability of the analyzer used. In smaller blood banks, where
manual work is often performed, the TAT is dependent on availability and
experience of staff, testing resources, and workload. Our site performed a
comparative analysis of the ORTHO VISION(r) (Ortho Clinical Diagnostics, Raritan,
NJ) and the Echo(r) (Immucor, Norcross, GA) blood bank analyzers, using the TAT
and PT of standard blood bank tests as the outcome metrics. Tests were run in
various combinations to reflect the standard workflow of a busy hospital
transfusion service and under routine and immediate or STAT conditions. We also
compared manual versus automated processing TATs for a variety of pre-transfusion
tests and antibody titers. We found that the capacity of the VISION to load and
run new samples, even while several other tests were ongoing, allowed for faster
overall TAT when compared with samples run on the Echo. The PTs of the two
analyzers (from load to result) were also compared, and we found them to be
equivalent. These findings highlight the inherent flaw in considering only PT
when assessing a laboratory's ability to efficiently and consistently make
results available to best meet customer and patient needs. In addition, we
observed a tighter distribution of TATs and PTs when the VISION was compared with
the Echo analyzer, providing a higher level of predictability for availability of
results. Finally, when compared with manual antibody titer testing, the VISION
analyzer showed a faster PT.
PMID- 28425749
TI - Hemolytic transfusion reaction attributable to anti-Dia.
AB - CONCLUSIONS: In situations when a patient's antibody detection test is negative,
many institutions have moved from an indirect antiglobulin test (IAT) crossmatch
to an electronic crossmatch system. Here we report a case of an acute hemolytic
transfusion reaction attributable to anti-Dia in a patient with a negative
antibody detection test. A 22-year-old female patient with a diagnosis of beta
thalassemia and sickle cell anemia commenced a routine exchange transfusion of 5
units of red blood cells (RBCs) in the apheresis unit as part of her regular
treatment. When the patient started receiving the implicated unit, she reported
back pain, chest pain, and a feeling of anxiety, suggestive of an acute
transfusion reaction. The transfusion was ceased and an investigation of an
adverse event was commenced. This case illustrates that the presence of
antibodies to low-prevalence antigens remains a significant issue for transfusion
dependent individuals. To prevent other transfusion reactions by anti-Dia, the
addition of Di(a+) cells to the reagent RBCs used for the antibody detection test
along with IAT-crossmatching of donor units for all patients with sickle cell
disease is recommended.
PMID- 28425750
TI - Modeling alloantibody formation to high-incidence red blood cell antigens in
immune responders using genotypic data.
AB - CONCLUSIONS: Alloimmunization to red blood cell antigens is unpredictable and
poorly understood. Patients who are negative for high-incidence antigens (HIAs)
are at risk for developing the corresponding antibodies. Molecular methods can
easily predict the lack of an antigen and thus, the risk of an individual to
become immunized. We examined the prevalence and risk factors for HIA
alloimmunization in patients at risk based on genotyping results. Genotyping
using a molecular method (HEA BeadChipTM, Immucor, Warren, NJ) was performed on
all patient specimens referred for molecular testing over 45 months; serologic
and clinical data were analyzed. We used simple and multiple logistic regression
to model the risk factors for alloimmunization to an HIA. Of the 2591 patients
genotyped, 32 (1.2%) were homozygous for at least one variant predicting absence
of an HIA. Of these 32 patients, prior transfusion or pregnancy history was
available for 29 (91%). Four susceptible patients made an antibody to an HIA
(12.5% of all, 13.8% of those with a documented exposure). Two of these four
patients (50%) had made an alloantibody to another antigen. The odds of forming
an antibody to an HIA were not related to the total number of transfusions (p =
0.47), the total number of alloantibodies (p = 0.61), or diagnosis of sickle cell
disease (p = 0.77) in simple logistic regression. Adjustment for the other two
variables in a multiple logistic regression was also not significant for each
variable (p = 0.6, p = 0.7, and p = 0.7, respectively). Although they had a known
exposure to alloantigens through transfusion or pregnancy, 86.2 percent of
patients (25 of 29) at risk for alloantibody formation to an HIA in fact did not
mount an immune response to that antigen. Possible risk factors including the
number of transfused units or the total number of alloantibodies made were not
predictors of making an alloantibody to an HIA in our sampling. Our results
suggest that other patient-specific risk factors for alloimmunization exist.
PMID- 28425751
TI - Development of red blood cell autoantibodies following treatment with checkpoint
inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated
with immune dysregulation.
AB - CONCLUSIONS: Ipilimumab, nivolumab, and pembrolizumab represent a new class of
immunotherapeutic drugs for treating patients with advanced cancer. Known as
checkpoint inhibitors, these drugs act to upregulate the cellular and humoral
immune response to tumor antigens by inhibiting T-cell autoregulation. As a
consequence, they can be associated with immune-related adverse events (irAEs)
due to loss of self-tolerance, including rare cases of immune-related cytopenias.
We performed a retrospective clinical chart review, including serologic,
hematology, and chemistry laboratory results, of two patients who developed red
blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor.
Serologic testing of blood samples from these patients during induction therapy
with ipilimumab and nivolumab, respectively, showed their RBCs to be positive by
the direct antiglobulin test (IgG+, C3+) and their plasma to contain panreactive
RBC autoantibodies. Neither patient had evidence of hemolysis. Both patients
developed an additional irAE during treatment. A literature review for patients
who had developed immune-mediated cytopenia following treatment with a checkpoint
inhibitor was performed. Nine other patients were reported with a hematologic
irAE, including six with anemia attributable to autoimmune anemia, aplastic
anemia, or pure RBC aplasia. Hematologic irAEs tend to occur early during
induction therapy, often coincident with irAEs of other organs. In conclusion,
checkpoint inhibitors can be associated with the development of autoantibodies,
immune-mediated cytopenias, pure RBC aplasia, and aplastic anemia.
Immunohematology reference laboratories should be aware of these agents when
evaluating patients with advanced cancer and new-onset autoantibodies, anemia,
and other cytopenias.
PMID- 28425752
TI - Use of standard laboratory methods to obviate routine dithiothreitol treatment of
blood samples with daratumumab interference.
AB - CONCLUSIONS: Daratumumab is an antibody currently used in the treatment of
patients with refractory multiple myeloma. Blood samples from patients being
treated with daratumumab may show panreactivity during pre-transfusion testing.
To facilitate the provision of blood components for such patients, it is
recommended that a baseline phenotype or genotype be established prior to
starting treatment with daratumumab. If patient red blood cells (RBCs) require
phenotyping after the start of daratumumab treatment, dithiothreitol (DTT)
treatment of the patient's RBCs should be performed. The medical charts of four
patients treated with daratumumab were reviewed. The individual number of doses
ranged from 1 to 14; patient age ranged from 55 to 78 years; two men and two
women were included in the review. Type and screen data were obtained from
samples collected over 33 encounters with a range of 1 to 13 encounters per
patient. All samples were tested initially by automated solid-phase testing. Any
reactivity with solid phase led to tube testing with either low-ionic-strength
saline, polyethylene glycol, or both. If incubation failed to eliminate the
reactivity, the sample was sent to a reference laboratory for DTT treatment and
phenotyping. Of the 33 samples tested, 23 (69.7%) samples had reactivity in solid
phase testing. In 8 of the 10 samples that did not react in solid-phase, testing
was conducted more than four half-lives after the last dose of daratumumab. Of
the 23 that had reactivity in solid-phase, 16 (69.6%) samples demonstrated loss
of reactivity using common laboratory methods. For the seven patients whose
sample reactivity was not initially eliminated, six were provided with
phenotypically matched blood based on prior molecular testing. Only one sample
was sent out for DTT treatment. These results suggest that daratumumab
interference with pre-transfusion testing can be addressed using common
laboratory methods. This finding could save time and money for laboratories that
do not have DTT available.
PMID- 28425753
TI - Applications of selected cells in immunohematology in a developing country: case
studies.
AB - CONCLUSIONS: When an antibody is detected, its specificity should be determined
and its likely clinical significance should be assessed. When one antibody has
been identified, it becomes necessary to confirm the presence of additional
significant antibodies to ensure that compatible blood is provided to the
patient. To perform this confirmation, specific reagent red blood cells (RBCs)
are selected; these are called selected cells. Though the most common use of
selected cells is for antibody confirmation, they can also be used for several
other immunohematologic applications. In a developing country like India, the
performance of antibody screening for unexpected antibodies on a routine basis is
a comparatively new phenomenon, and those laboratories performing advanced
immunohematologic testing would need to use selected cells to arrive at an
accurate conclusion. This report defines selected cells and enumerates sources of
these RBCs. Detailed immunohematologic applications are discussed with applicable
case studies.
PMID- 28425755
TI - Thrombus aspiration in acute coronary syndromes: prevalence, procedural success,
change in serial troponin T levels and clinical outcomes in a contemporary Swiss
cohort.
AB - BACKGROUND: Randomised controlled trials have provided conflicting results
regarding procedural and clinical outcomes of thrombus aspiration combined with
percutaneous coronary intervention, when compared with primary percutaneous
coronary intervention alone in patients with acute coronary syndromes. METHODS:
Acute coronary syndrome patients referred for coronary angiography to four Swiss
university hospitals between 2009 and 2012 were enrolled in the SPUM-ACS cohort.
At the discretion of the interventional cardiologist, patients underwent thrombus
aspiration with percutaneous coronary intervention or percutaneous coronary
intervention alone. Procedural success was defined as post-procedural
thrombolysis in myocardial infarction III flow in the infarct-related artery.
Serial changes in high-sensitivity troponin T (DeltahsTnT) and adjudicated 30
days (1 year) clinical events defined as the composite of cardiac death,
recurrent myocardial infarction or clinically indicated coronary
revascularisation were assessed. RESULTS: Among 1641 patients, 777 (47.4%) had
angiographic evidence of coronary thrombus. Patients were categorised into
thrombus aspiration with percutaneous coronary intervention ( n=663) or
percutaneous coronary intervention alone ( n=114). ST-segment elevation
myocardial infarction (STEMI) patients more often received thrombus aspiration
with percutaneous coronary intervention (87.8%) than non-STEMI patients (73.5%),
P<0.001. Procedural success was not different in thrombus aspiration with
percutaneous coronary intervention compared with percutaneous coronary
intervention alone (93.8% vs. 90.7%, P=0.243). DeltahsTnT was similar in STEMI
patients (3.09+/-4.52 vs. 2.19+/-4.92 ug/l, P=0.086) as was clinical outcome in
the entire cohort at 30 days (2.9% vs. 3.6%, P=0.76) and 1 year (7.2% vs. 5.3%,
P=0.55) regardless of whether thrombus aspiration was used during primary
percutaneous coronary intervention or not. CONCLUSIONS: In this real-world acute
coronary syndrome cohort, patients treated by thrombus aspiration with
percutaneous coronary intervention showed no difference in the restoration of
coronary blood flow compared with percutaneous coronary intervention alone
immediately after the procedure. Furthermore, DeltahsTnT and clinical outcomes at
either 30 days or 1 year were similar between thrombus aspiration with
percutaneous coronary intervention or percutaneous coronary intervention alone.
CLINICAL TRIALS REGISTRATION: SPUM-ACS cohort NCT01000701.
PMID- 28425754
TI - Immunotherapy and targeted therapy in brain metastases: emerging options in
precision medicine.
AB - Brain metastases (BM) continue to represent an unmet clinical need in oncology.
Immunotherapy and targeted therapy hold great promise in the treatment of BM.
Emerging data are confirming the activity of these agents in patients with BM.
Genomic studies have confirmed that clinically actionable mutations are present
in BM and they can be used in clinical studies to link targeted therapies with
their genetic targets. Furthermore, as molecular signatures associated with
sensitivity and resistance to immunotherapies are developed, we will better be
able to select BM patients who will most benefit from these therapies.
Understanding the genetic and immune evolution within BM should drive the next
generation of immunotherapy and target therapy, as well as increase the accuracy
of the selection process for these therapies.
PMID- 28425756
TI - CNS hemangioblastomatosis in a patient without von Hippel-Lindau disease.
AB - We report on a case of disseminated CNS hemangioblastoma, also referred to as
hemangioblastomatosis, involving the supratentorial compartment and the entire
spine. The patient presented with new onset headache, gait difficulties and
memory deficits many years following resection of a hemangioblastoma from the
cerebellum. The patient's family history was negative for von Hippel-Lindau (VHL)
disease, and his personal history was negative for any additional VHL-defining
lesions. Imaging revealed extensive dural caking and nodularity both
supratentorially and in the spine, along with scattered parenchymal tumors
showing a more typical appearance for hemangioblastoma. Biopsy of the dural
thickening revealed histologic features compatible with hemangioblastoma. Genetic
testing for VHL was eventually completed, and no evidence of a germline VHL
mutation was detected.
PMID- 28425757
TI - The prevalence and characteristics of a subcortical cystic lesion at the
subspinous region of the knee.
AB - Background Although we observed that subcortical cysts near the attachment of the
meniscus or cruciate ligaments are frequently seen with a tear or degeneration of
the adjacent meniscus and/or cruciate ligament, there is no large study
describing the prevalence, distribution, and associated findings of these cysts.
Purpose To evaluate the prevalence and distribution of subcortical cysts near the
attachments of the meniscus or cruciate ligaments and evaluate pathologies of the
meniscus or cruciate ligaments using magnetic resonance imaging (MRI). Material
and Methods We reviewed 1009 knee MRIs for the presence of subcortical cysts near
the meniscus or cruciate ligament attachments and evaluated their size, location,
edema of the adjacent bone marrow, and integrities of the medial and lateral
meniscus and anterior and posterior cruciate ligaments. Results The 110 cysts
were found in either the middle (n = 56), posterior (n = 52), or anterior (n = 2)
subspinous regions. Sixty-two were at meniscal root insertion, including seven at
the lateral meniscus anterior horn, five at the lateral meniscus posterior horn,
48 at the medial meniscus posterior horn, and two at the medial meniscus anterior
horn. All were associated with an adjacent meniscal pathology. Of the 34 cysts at
the anterior cruciate ligament (ACL) insertion, 28 had ACL pathology. Nine cysts
had surrounding edema in the adjacent bone marrow. Conclusion Subcortical cysts
at the subspinous region of the knee were seen in 9.6% of knee MRI examinations.
Most were in close proximity to the meniscal or cruciate ligaments with
associated pathologies, suggesting that abnormal stress on the bone induces cyst
formation.
PMID- 28425758
TI - Agreement between MRI and pathologic analyses for determination of tumor size and
correlation with immunohistochemical factors of invasive breast carcinoma.
AB - Background There may be discordance between tumor size determined by magnetic
resonance imaging (MRI) and that observed during pathologic analyses. Purpose To
evaluate MRI-pathology concordance of tumor size in patients with invasive breast
carcinoma. Material and Methods Data from 307 invasive breast carcinomas were
analyzed retrospectively. Preoperative breast MRI was reviewed for size, lesion
type, morphology, and dynamic contrast-enhanced tumor kinetics. MRI tumor size
was compared with tumor size measurements from the pathologic analysis.
Concordance was defined as a difference in diameter of <= 0.5 cm. MRI-pathology
concordance was compared according to clinical and histopathologic features.
Results The mean tumor size on MRI was 2.48 +/- 1.41 cm. Tumor measurements
determined by MRI were not significantly different from those recorded in the
pathologic reports (2.56 +/- 1.61 cm, P = 0.199). MRI-pathology concordance was
found in 229/307 (74.6%) cases; the size was overestimated in 36 (11.7%) tumors
and underestimated in 42 (13.7%). On univariate analysis, MRI-pathology
discordance was associated with larger tumor size ( P < 0.001), estrogen receptor
(ER) negativity ( P = 0.006), and lymphovascular invasion ( P = 0.003). Human
epidermal growth factor receptor 2 positive molecular subtype showed worse
correlation between the tumor size measured by MRI and pathology compared with
luminal A and luminal B subtypes ( P = 0.008 and 0.007). On multivariate
analysis, tumor size and ER status significantly influenced MRI-pathology
concordance ( P < 0.05). Conclusion ER negativity and larger tumor size were
strongly associated with MRI-pathology discordance in invasive breast carcinomas.
Awareness of these factors might improve surgical planning.
PMID- 28425759
TI - Speech pathology as the MasterChef: Getting the right ingredients and stirring
the pot.
AB - The purpose of this paper is to consider the many influences that have an impact
on appropriate speech-language pathology service delivery. The competitive
cooking and entertainment television program, MasterChef, is used as an analogy
to consider the ingredients, blend and approach required to improve speech
language pathology services. Speech-language pathologists (SLPs) enter the
profession with the aim of assisting those with communication and swallowing
disorders to have a better quality of life. Thus, we should be restless to
continue to improve our services in order to achieve the best influence and
outcomes by changing our recipes and ingredients. However, having good technical
skills as a SLP is not sufficient in ensuring that the services are the best they
can be. We have to consider available resources, customers and service users, who
it is that judges our services, whether we are as good as we could or should be,
what can help us improve our services, what the appetite is for our services, and
how we incorporate evidence-based practice. This paper considers the value of
understanding and using information on incidence and prevalence, evidence-based
practice and outcome measurement. Blending technical, clinical and academic
abilities with personal skills will result in an award-winning menu.
PMID- 28425760
TI - Polar-phase indices of perioral muscle reciprocity during syllable production in
Parkinson's disease.
AB - PURPOSE: This research characterised perioral muscle reciprocity and amplitude
ratio in lower lip during bilabial syllable production [pa] at three rates to
understand the neuromotor dynamics and scaling of motor speech patterns in
individuals with Parkinson's disease (PD). METHOD: Electromyographic (EMG)
signals of the orbicularis oris superior [OOS], orbicularis oris inferior [OOI]
and depressor labii inferioris [DLI] were recorded during syllable production and
expressed as polar-phase notations. RESULT: PD participants exhibited the general
features of reciprocity between OOS, OOI and DLI muscles as reflected in the EMG
during syllable production. The control group showed significantly higher
integrated EMG amplitude ratio in the DLI:OOS muscle pairs than PD participants.
No speech rate effects were found in EMG muscle reciprocity and amplitude
magnitude across all muscle pairs. CONCLUSION: Similar patterns of muscle
reciprocity in PD and controls suggest that corticomotoneuronal output to the
facial nucleus and respective perioral muscles is relatively well-preserved in
our cohort of mild idiopathic PD participants. Reduction of EMG amplitude ratio
among PD participants is consistent with the putative reduction in the
thalamocortical activation characteristic of this disease which limits motor
cortex drive from generating appropriate commands which contributes to
bradykinesia and hypokinesia of the orofacial mechanism.
PMID- 28425761
TI - Adult pilocytic astrocytoma of conus medullaris: clinical considerations and
review of the literature.
AB - Astrocytomas are responsible for 30% of all primitive intramedullary tumors with
cervicothoracic predominance. However, only about one hundred cases of
intramedullary pilocytic astrocytomas were described. The authors described the
case of a 69 year-old patient presenting with a broad-base gait, bilateral pain
and dysesthesia of inferior limbs with a diagnosis of an intra-axial cystic
lesion centered to the conus medullaris, diagnosed as pilocytic astrocytoma of
conus medullaris (PACM) after surgery. To the best of our knowledge, only two
previous reports concerning PACM were made. As benign lesions associated with
long survivals, function should be the mainstay of treatment of PACM. Surgical
resection should be performed. Adjuvant radiotherapy or chemotherapy has no
establish role in pilocytic astrocytic lesions.
PMID- 28425762
TI - The evaluation of bulbar dysfunction in amyotrophic lateral sclerosis: survey of
clinical practice patterns in the United States.
AB - OBJECTIVE: Speech and swallowing impairments are highly prevalent in individuals
with amyotrophic lateral sclerosis (ALS) and contribute to reduced quality of
life, malnutrition, aspiration, pneumonia and death. Established practice
parameters for bulbar dysfunction in ALS do not currently exist. The aim of this
study was to identify current practice patterns for the evaluation of speech and
swallowing function within participating Northeast ALS clinics in the United
States. METHODS AND RESULTS: A 15-item survey was emailed to all registered NEALS
centres. Thirty-eight sites completed the survey. The majority (92%) offered
Speech-Language Pathology, augmentative and alternative communication (71%), and
dietician (92%) health care services. The ALS Functional Rating Scale-Revised and
body weight represented the only parameters routinely collected in greater then
90% of responding sites. Referral for modified barium swallow study was routinely
utilised in only 27% of sites and the use of percutaneous gastrostomy tubes in
ALS patient care was found to vary considerably. CONCLUSIONS: This survey reveals
significant variability and inconsistency in the management of bulbar dysfunction
in ALS across NEALS sites. We conclude that a great need exists for the
development of bulbar practice guidelines in ALS clinical care to accurately
detect and monitor bulbar dysfunction.
PMID- 28425764
TI - BRAF-V600E mutant papillary craniopharyngioma dramatically responds to
combination BRAF and MEK inhibitors.
AB - We present a patient with BRAF-V600E mutant papillary craniopharyngioma
successfully treated with combination BRAF (dabrafenib 150 mg twice daily) and
MEK (trametinib 2 mg daily) inhibitors after her unresectable tumor proved
refractory to radiation. Serial brain MRIs and PET revealed marked tumor
reduction with gradual neurological improvement and permanent panhypopituitarism.
PMID- 28425765
TI - The prevention and treatment of venous thromboembolism in pregnancy.
AB - INTRODUCTION: Venous thromboembolism (VTE) in pregnancy represents an important
cause of maternal morbidity and mortality in developed countries, with an
incidence of 0.5-2.2 per 1000 pregnancies. In addition to hemostatic changes
occurring during normal pregnancy, several risk factors have been identified.
Thus, a variety of clinical conditions as well as fetal and maternal risks linked
to a possible anticoagulant therapy should be considered for the management of
VTE during pregnancy. Unfortunately, there is a paucity of high-quality evidence
from randomized trials in this field, and current recommendations are based on
observational studies or evidence gathered from studies in the non-pregnant
population. Areas covered: The purpose of this review is to summarize available
evidence on the prevention and treatment of pregnancy-related VTE. Expert
commentary: Although the optimal prophylactic and therapeutic dosage has not yet
been established, low-molecular-weight heparin (LMWH) represents the most
efficacious and safe anticoagulant during pregnancy. Thus, after an accurate risk
stratification of women during pregnancy and puerperium, LMWH should be
recommended to women at risk for VTE and to those ones suffering from an acute
event.
PMID- 28425766
TI - Update in the treatment of non-influenza respiratory virus infection in solid
organ transplant recipients.
AB - INTRODUCTION: Despite the improved outcomes in solid organ transplantation with
regard to prevention of rejection and increased patient and graft survival,
infection remains a common cause of morbidity and mortality. Respiratory viruses
are a frequent and potentially serious cause of infection after solid organ
transplantation. Furthermore, clinical manifestations of respiratory virus
infection (RVI) may be more severe and unusual in solid organ transplant
recipients (SOTRs) compared with the non-immunocompromised population. Areas
covered: This article reviews the non-influenza RVIs that are commonly
encountered in SOTRs. Epidemiologic and clinical characteristics are highlighted
and available treatment options are discussed. Expert opinion: New diagnostic
tools, particularly rapid molecular assays, have expanded the ability to identify
specific RVI pathogens in SOTRs. This is not only useful from a treatment
standpoint but also to guide infection control practices. More data are needed on
RVIs in the solid organ transplant population, particularly regarding their
effect on rejection and graft dysfunction. There is also a need for new antiviral
agents active against these infections as well as markers that can identify which
patients would most benefit from treatment.
PMID- 28425767
TI - Chronic total coronary occlusion: treatment results.
AB - OBJECTIVES: To describe the clinical and procedural coronary chronic total
occlusion (CTO) treatment results in a Nordic PCI centre during the
implementation of a CTO treatment program. DESIGN: In a retrospective registry
study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular
Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart
failure score, (3) lesion complexity and (4) adverse events during hospital stay
and three months following the index procedure. RESULTS: The study cohort
included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were
performed with antegrade wire-escalation technique and 4% performed using
retrograde techniques, from 2013-2016 the corresponding numbers were 83% and
17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p
= .06) after routinely using the retrograde approach. No individual patient
characteristic, lesion variable or score was strongly associated with procedural
success or failure. There were 4% serious procedure related complications. In
patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class
>=2 before the index procedure vs. 22% at follow-up. CONCLUSIONS: Routine use of
retrograde techniques tended to increase the procedural success rate. Clinical
results after three months were acceptable, but the complication rate was higher
than for non-CTO PCI. Individual patient and lesion characteristics had a low
predictability for procedural success. Therefore, clinical symptoms, objective
signs of myocardial ischemia and procedural risk should be focus points in
coronary chronic total occlusion treatment strategies.
PMID- 28425769
TI - Convergent and Divergent Validity Between the KTK and MOT 4-6 Motor Tests in
Early Childhood.
AB - The aim of this study was to investigate the convergent and divergent validity
between the Body Coordination Test for Children (KTK) and the Motor Proficiency
Test for 4- to 6-Year-Old Children (MOT 4-6). A total of 638 children (5-6 yr
old) took part in the study. The results showed a moderately positive association
between the total scores of both tests (rs = .63). Moreover, the KTK total score
correlated more highly with the MOT 4-6 gross motor score than with the MOT 4-6
fine motor score (rs = .62 vs. .32). Levels of agreement were moderate when
identifying children with moderate or severe motor problems and low at best when
detecting children with higher motor-competence levels. This study provides
evidence of convergent and divergent validity between the KTK and MOT 4-6.
However, given the moderate to low levels of agreement, either measurement may
lead to possible categorization errors. Therefore, it is recommended that
children's motor competence not be judged based on the result of a single test.
PMID- 28425770
TI - Measuring Fine Motor Skills in Children with Visual Impairments.
PMID- 28425771
TI - Review of stereotactic radiosurgery for intradural spine tumors.
AB - Stereotactic radiosurgery (SRS) has become an increasingly popular treatment
modality for spinal tumors due to its noninvasive and targeted approach. Whether
SRS has the promise of relieving pretreatment symptoms and providing local tumor
control for patients with intradural spine tumors is still debated. This review
explores the current literature on SRS treatment for both metastatic and benign
intradural tumors, with a focus on differential use for intramedullary and
intradural extramedullary neoplasms. Although mortality rates from underlying
malignant disease remain high, SRS may benefit patients with spinal metastatic
lesions. Benign tumors have shown a promising response to SRS therapy with low
rates of complications. Larger studies are necessary to determine the indications
and outcome profile of SRS for intradural spinal neoplasms.
PMID- 28425772
TI - Prediction of successful dose reduction or discontinuation of adalimumab,
etanercept, or infliximab in rheumatoid arthritis patients using serum drug
levels and antidrug antibody measurement.
AB - BACKGROUND: To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug
antibodies (ADAb) can predict successful dose reduction (in patients with high
DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid
arthritis (RA) patients. RESEARCH DESIGN AND METHODS: RA patients that were using
adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing
well, were tapered until discontinuation or flare (1-1.5 year follow up). Random
timed DL for adalimumab and etanercept and trough DL for infliximab were measured
before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut
off DL were determined. RESULTS: No predictive value of adalimumab and infliximab
DL for all outcomes were found, except for an inverse association of lower
etanercept DL and higher chance for successful dose reduction (Area Under the
Curve (AUC) 0.36, 95% CI 0.23-0.49; cut-off <2.6 mg/l). In sub analyses, higher
adalimumab trough DL predicted successful dose reduction (AUC 0.86, 0.58-1.00;
cut-off >7.8). ADAb were infrequent and not predictive of successful
discontinuation. CONCLUSIONS: No predictive value of baseline adalimumab,
etanercept and infliximab DL or ADAb for successful dose reduction or
discontinuation in RA was found in this context, with the possible exception of
high adalimumab trough levels for successful dose reduction.
PMID- 28425773
TI - Prognostic value of pre- and post-treatment health-related quality of life in
predicting survival of patients with brain metastases.
AB - AIM: The present study aimed to determine the prognostic survival value of
pretreatment health-related quality of life (HRQOL) and changes in HRQOL
following whole-brain radiation treatment in patients with brain metastases.
METHODS: Patients who were treated with whole-brain radiation treatment and
completed HRQOL questionnaires were included. Univariate and multivariate Cox
proportional hazard models of overall survival (OS) were conducted for overall
HRQOL and domain scores. RESULTS & CONCLUSION: Patients with lower HRQOL at
baseline, especially lower physical functioning and motor dysfunction domains,
were more likely to have poorer survival. Changes in overall HRQOL and its
domains were not significantly related to OS. Pretreatment HRQOL, especially
physical functioning and motor dysfunction, has added prognostic value in
patients with brain metastases.
PMID- 28425774
TI - Profile of the triplex assay for detection of chlamydia, gonorrhea and
trichomonas using the BD MAXTM System.
AB - INTRODUCTION: Chlamydia, gonorrhea and trichomonas are the most common curable
STI. improved access to testing could reduce infection rates and prevent
sequelae. nucleic acid amplification tests are the recommend class of diagnostic
assay for these infections which are often asymptomatic. Areas covered: A
description of the BD MAXTM System (MAX) and the BD MAX CT/GC/TV assay is
provided along with data from a large US clinical trial. The capacity of the
system for other tests and for lab developed assays is also described. Expert
commentary: The CT/GC/TV assay on the MAX is a triplex PCR assay suitable for use
with female urine and vaginal or endocervical swab samples. Male urine can be
tested by ordering the CT/GC results but has not yet been evaluated for
trichomonas. The assay performance characteristics are similar to those of assays
run on high-throughput platforms with sensitivity >=91.5% and specificity >=98.6%
for all analytes. Screening with the CT/GC/TV assay can be combined with testing
for vaginitis which would provide a greater depth of coverage for common co
infections. The throughput is moderate (1-48 samples per 8-hour shift) but the
menu includes assays beyond STI pathogens making this a suitable platform for
moderate volume laboratories.
PMID- 28425775
TI - Academic outcomes of multilingual children in Australia.
AB - PURPOSE: The Australian educational system is increasingly challenged to meet the
needs of multilingual students, who comprise a fifth of the student population.
Within the context of a monolingual English curriculum, multilingual children who
enter school not yet English proficient may be at risk of experiencing
inequitable educational outcomes. METHOD: We examined the relationship between
the timing of multilingual children's acquisition of receptive English vocabulary
skills and subsequent reading and numeracy outcomes, as well as factors
associated with earlier versus later timing of acquisition. Data were drawn from
the Kindergarten-cohort (n = 4983) of the Longitudinal Study of Australian
Children - a nationally representative, community sample of Australian children.
RESULT: Linear regression analyses revealed that multilingual children who begin
school with proficient receptive English vocabulary skills, or who acquire
proficiency early in schooling, are indistinguishable from their monolingual
peers in literacy and numeracy outcomes by 10-11 years. However, later
acquisition of receptive English vocabulary skills (i.e. after 6-7 years) was
associated with poorer literacy outcomes. In turn, socioeconomic disadvantage and
broader language or learning problems predicted this later acquisition of
receptive English vocabulary skills. CONCLUSION: All children need to be
supported during the early years of school to reach their full educational
potential.
PMID- 28425776
TI - Development of the Aboriginal Communication Assessment After Brain Injury
(ACAABI): A screening tool for identifying acquired communication disorders in
Aboriginal Australians.
AB - PURPOSE: Acquired communication disorders (ACD), following stroke and traumatic
brain injury, may not be correctly identified in Aboriginal Australians due to a
lack of linguistically and culturally appropriate assessment tools. Within this
paper we explore key issues that were considered in the development of the
Aboriginal Communication Assessment After Brain Injury (ACAABI) - a screening
tool designed to assess the presence of ACD in Aboriginal populations. METHOD: A
literature review and consultation with key stakeholders were undertaken to
explore directions needed to develop a new tool, based on existing tools and
recommendations for future developments. RESULT: The literature searches revealed
no existing screening tool for ACD in these populations, but identified tools in
the areas of cognition and social-emotional wellbeing. Articles retrieved
described details of the content and style of these tools, with recommendations
for the development and administration of a new tool. The findings from the
interview and focus group views were consistent with the approach recommended in
the literature. CONCLUSIONS: There is a need for a screening tool for ACD to be
developed but any tool must be informed by knowledge of Aboriginal language,
culture and community input in order to be acceptable and valid.
PMID- 28425778
TI - Meditation awareness training for the treatment of workaholism: A controlled
trial.
AB - Background and aims Workaholism is a form of behavioral addiction that can lead
to reduced life and job satisfaction, anxiety, depression, burnout, work-family
conflict, and impaired productivity. Given the number of people affected, there
is a need for more targeted workaholism treatments. Findings from previous case
studies successfully utilizing second-generation mindfulness-based interventions
(SG-MBIs) for treating behavioral addiction suggest that SG-MBIs may be suitable
for treating workaholism. This study conducted a controlled trial to investigate
the effects of an SG-MBI known as meditation awareness training (MAT) on
workaholism. Methods Male and female adults suffering from workaholism (n = 73)
were allocated to MAT or a waiting-list control group. Assessments were performed
at pre-, post-, and 3-month follow-up phases. Results MAT participants
demonstrated significant and sustained improvements over control-group
participants in workaholism symptomatology, job satisfaction, work engagement,
work duration, and psychological distress. Furthermore, compared to the control
group, MAT participants demonstrated a significant reduction in hours spent
working but without a decline in job performance. Discussion and conclusions MAT
may be a suitable intervention for treating workaholism. Further controlled
intervention studies investigating the effects of SG-MBIs on workaholism are
warranted.
PMID- 28425777
TI - Self-reported dependence on mobile phones in young adults: A European cross
cultural empirical survey.
AB - Background and aims Despite many positive benefits, mobile phone use can be
associated with harmful and detrimental behaviors. The aim of this study was
twofold: to examine (a) cross-cultural patterns of perceived dependence on mobile
phones in ten European countries, first, grouped in four different regions
(North: Finland and UK; South: Spain and Italy; East: Hungary and Poland; West:
France, Belgium, Germany, and Switzerland), and second by country, and (b) how
socio-demographics, geographic differences, mobile phone usage patterns, and
associated activities predicted this perceived dependence. Methods A sample of
2,775 young adults (aged 18-29 years) were recruited in different European
Universities who participated in an online survey. Measures included socio
demographic variables, patterns of mobile phone use, and the dependence subscale
of a short version of the Problematic Mobile Phone Use Questionnaire (PMPUQ;
Billieux, Van der Linden, & Rochat, 2008). Results The young adults from the
Northern and Southern regions reported the heaviest use of mobile phones, whereas
perceived dependence was less prevalent in the Eastern region. However, the
proportion of highly dependent mobile phone users was more elevated in Belgium,
UK, and France. Regression analysis identified several risk factors for increased
scores on the PMPUQ dependence subscale, namely using mobile phones daily, being
female, engaging in social networking, playing video games, shopping and viewing
TV shows through the Internet, chatting and messaging, and using mobile phones
for downloading-related activities. Discussion and conclusions Self-reported
dependence on mobile phone use is influenced by frequency and specific
application usage.
PMID- 28425779
TI - Prevention paradox logic and problem gambling: Does low-risk gambling impose a
greater burden of harm than high-risk gambling?
AB - Background and aims The aim of this paper is to examine the evidence and
arguments in favor of prevention paradox (PP) logic in the context of problem
gambling. Evidence from recent studies of gambling and the distribution of harm
across lower and higher risk gamblers is reviewed to examine the contention that
the absolute burden of harm is greater in low-risk (LR) gamblers than the problem
gamblers. Methods The review examines a number of methodological and conceptual
concerns about existing evidence in support of the PP. Results The principal
problems identified include the misclassification of LR gamblers; the use of
binary scoring method that understates the frequency of harms in high-risk
populations; a tendency to confuse behavior and harm; and the use of potentially
overly inclusive definitions of harm with low thresholds of severity. Discussion
and conclusions This paper makes a number of recommendations for enhancement of
this area of research, including the use of clear definitions of harm and LR
behavior and a greater focus on harm with material impacts on people's quality of
life.
PMID- 28425780
TI - Endothelium-dependent Vasodilation in Hypertension: A Review.
AB - Using both in vitro and in vivo techniques, it has repeatedly been shown that
endothelium-dependent vasodilation (EDV) is impaired in different forms of
experimental hypertension (SHR, Dahl salt-sensitive rat, DOCA-salt rat and
renovascular hypertension). EDV has also been found to be impaired in primary, as
well as in secondary forms of human hypertension. Although impaired EDV is a
general finding in hypertension, the pathophysiological mechanisms might differ
between different forms of hypertension and between different types of vessels
and vascular beds. Impaired activity of nitric oxide synthase, increased release
of endothelin-1, increased production of a prostanoid-derived contracting factor,
decreased generation of endothelium-derived hyperpolarizing factor/s and
impairment caused by superoxide ions have all been shown to contribute to the
impairment of EDV during different conditions. While most antihypertensive
treatments improve EDV in experimental hypertension, no uniform picture has been
seen in human hypertension, possibly because different antihypertensive drugs
have different direct actions on EDV. This review shows that while impaired EDV
has been found to be a general feature of hypertension, the mechanisms involved
and the therapeutic opportunities have still to be established.
PMID- 28425781
TI - Endothelial Dysfunction - A Challenge for Hypertension Research.
PMID- 28425782
TI - Cerebral Perfusion in Hypertensives with Carotid Artery Stenosis: A Comparative
Study of Lacidipine and Hydrochlorothiazide.
PMID- 28425783
TI - Effects of hormone replacement therapy on ambulatory blood pressure and vascular
responses in normotensive women.
AB - The effects of chronic oestrogen replacement therapy (ERT) (conjugated equine
oestrogen 0.625 mg/day) and combined oestrogen and progestogen replacement
therapy (HRT) (ERT plus continuous medroxyprogesterone acetate 5 mg/day) on 24-h
ambulatory blood pressure recordings, forearm vascular resistance (FVR) and FVR
responses to noradrenaline, angiotensin II, acetylcholine and nitroprusside were
studied in 17 normotensive postmenopausal women in a 3-month randomized, double
blind, placebo-controlled crossover trial with 1 month of therapy in each
treatment arm. During the last few days of each 1-month treatment period, the
subjects underwent 24-h ambulatory blood pressure recordings and measurements of
FVR responses. ERT and HRT reduced mean 24-h diastolic blood pressure by 4 and 5
mmHg, systolic blood pressure by 6 and 9 mmHg and mean 24-h heart rate by 5 and 3
beats/min, respectively for ERT and HRT (p < 0.05). Basal FVR was reduced by
approximately 18% by ERT and HRT, but FVR responses to noradrenaline, angiotensin
II, acetylcholine and nitroprusside were unaffected. ERT and HRT therapy for 1
month lowers blood pressure and basal FVR, but does not appear to influence FVR
responses to acetylcholine, nitroprusside, noradrenaline and angiotensin II.
PMID- 28425784
TI - Vascular Endothelial Cell Activation Associated with Increased Plasma Asymmetric
Dimethyl Arginine in Children and Young Adults with Hypertension: A Basis for
Atheroma?
AB - The mechanism behind the development of vascular complications of hypertension in
the young human remains unclear. To explore the role of vascular endothelium
generated nitric oxide (a known mediator of leucocyte-platelet-endothelial
interactions) in this context, we investigated markers of endothelial activation
(soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion
molecule-1 (ICAM-1), P-selectin, E-selectin), and von Willebrand factor and the
plasma level of the endogenous nitric oxide inhibitor asymmetric dimethyl
arginine (ADMA) in a group of 31 (17 male, mean age 9.4 years) hypertensive and 9
(4 male, mean age 9.1 years) healthy, normotensive children and young adults. We
found raised levels of ADMA (mean (SEM) 235 (32) n mol/l) and VCAM-1 (median
(range) 1237 (675-2700) ng/ml) in the plasma of hypertensive subjects compared
with those of normotensives (ADMA, 103 (7) n mol/l and VCAM-1, 1005 (425-1650)
ng/ml, respectively). Furthermore, in hypertensive subjects, higher VCAM-1
concentrations (r = 0.66, p < 0.001) and vWF concentrations (r = 0.37, p = 0.04)
were significantly associated with a higher plasma ADMA level. Therefore, an
isolated increase in plasma VCAM-1 in hypertensives in association with raised
ADMA may signify a selective ?non-inflammatory? endothelial activation triggered
by endothelial nitric oxide synthase inhibition. Since VCAM-1 is implicated in
the origins of atherosclerosis, ADMA may be an important contributory factor in
increasing the risk of atheroma formation in hypertensive children and young
adults.
PMID- 28425785
TI - Lack of Association of Angiotensin-converting Enzyme and Angiotensinogen Genes
Polymorphisms with Left Ventricular Structure in Young Normotensive Men.
PMID- 28425786
TI - Organ damage in treated middle-aged hypertensives compared to normotensives:
results from a cross-sectional study in general practice.
AB - BACKGROUND: High blood pressure contributes to organ damage. However, during the
past two decades there have been great advances in the medical treatment of
hypertension. Technical progress has also made it easier to visualize organ
damage. Hence we found it of interest to examine heart, brain and retina in a
group of middle-aged treated hypertensives, comparing the results with those from
a group of middle-aged normotensives. METHODS: The subjects were 40 (20 men)
treated hypertensives and 40 (20 men) normotensives, who had previously taken
part in a study in which ambulatory blood pressure monitoring had been performed.
The heart was examined by echocardiography, the retina by photography and the
brain by magnetic resonance imaging. RESULTS: Office blood pressure and 24-h
systolic/diastolic blood pressure (S/D) were 141/86 (13/7) mmHg and 128/81 (11/6)
mmHg in the hypertensives and 125/78 -(10/8) mmHg and 118/74 (8/5) mmHg in the
normotensives, respectively. Left ventricular mass was 101 (27) g/m2 in the
hypertensives and 85 (18) g/m2 in the normotensives (p = 0.0025). The
corresponding figures for the left atrium were 21.1 (3.1) mm/m2 in the
hypertensives and 19.5 (2.2) mm/m2 in the normotensives (p < 0.001). E/A wave
quotient was 1.09 (0.26) in the hypertensives and 1.26 (0.26) in the
normotensives (p = 0.0045), while left ventricular systolic function did not
differ between the groups. Ten hypertensives and one normotensive subject had
left ventricular mass above normal range. Narrow retinal arteries were found in
22 hypertensives and 8 normotensives (p < 0.001). Brain magnetic resonance
changes (deep white matter and/or periventricular) were found in 19 hypertensives
and 9 normotensives (p = 0.0431). CONCLUSIONS: The hypertensives differed
significantly from the normotensives concerning left ventricular mass, left
atrium, left ventricular diastolic function and retinal vessel changes. Deep
white matter and periventricular changes in the brain were also significantly
different in the two groups. We can only speculate as to whether earlier
antihypertensive treatment or further blood pressure reduction could have
affected these differences.
PMID- 28425787
TI - Defining the proteomic landscape of rheumatoid arthritis: progress and
prospective clinical applications.
AB - INTRODUCTION: The heterogeneity of Rheumatoid Arthritis (RA) and the absence of
clinical tests accurate enough to identify the early stages of this disease have
hampered its management. Therefore, proteomics research is increasingly focused
on the discovery of novel biological markers, which would not only be able make
an early diagnosis, but also to gain insight into the different pathological
mechanisms underlying the heterogeneity of RA and also to stratify patients,
which is critical to enabling effective treatments. Areas covered: The proteomic
approaches that have been utilised to provide knowledge about RA pathogenesis,
and to identify biomarkers for RA diagnosis, prognosis, disease monitoring and
prediction of response to therapy, are summarized. Expert commentary: Although
each proteomic study is unique in its design, all of them have contributed to the
understanding of RA pathogenesis and the discovery of promising biomarkers for
patient stratification, which would improve clinical care of RA patients. Still,
efforts need to be made to validate these findings and translate them into
clinical practice.
PMID- 28425788
TI - The Outcome of STOP-Hypertension-2 in Relation to the 1999 WHO/ISH Hypertension
Guidelines.
AB - The 1999 hypertension management guidelines issued by the World Health
Organization and the International Society of Hypertension emphasize the
importance of blood pressure reduction in the prevention of cardiovascular
events. Furthermore, they conclude that the benefits of treatment are due to
blood pressure lowering per se, rather than to any specific antihypertensive
therapy. The results of the second Swedish Trial in Old Patients with
Hypertension (STOP-Hypertension-2) are consistent with these recommendations,
since in this trial angiotensin converting enzyme (ACE) inhibitors and calcium
antagonists reduced blood pressure to the same extent as conventional therapy
with beta-blockers and diuretics in elderly hypertensive patients, and the three
treatments produced similar reductions in the risk of cardiovascular events.
Furthermore, a first subgroup analysis of cardiovascular mortality showed that
the three treatments seemed equally effective in diabetic patients. The STOP
Hypertension-2 data, therefore, are fully consistent with the 1999 hypertension
management guidelines, and underline the advantages offered by both older and
newer antihypertensive therapies.
PMID- 28425789
TI - The Problem of Hypertension in the Elderly.
AB - Since most developed countries have an ageing population, the prevalence of
hypertension is increasing. This age-driven increase in cardiovascular risk is an
important factor contributing to the increasing burden of mortality and morbidity
associated with cardiovascular disease. Today, there is a strong rationale for an
aggressive approach to hypertension since antihypertensive treatment has been
shown to reduce cardiovascular mortality and morbidity in the elderly. It is
likely that increasing emphasis will be placed on control of isolated and
borderline systolic hypertension, which are the predominant forms of hypertension
in elderly patients. The recent second Swedish Trial in Old Patients with
Hypertension (STOP-Hypertension-2) represents an important contribution to the
literature since it shows that newer antihypertensive agents, such as angiotensin
converting enzyme (ACE) inhibitors and calcium antagonists, are as effective as
older agents in reducing cardiovascular mortality and morbidity in elderly
patients.
PMID- 28425790
TI - Results of the STOP-Hypertension-2 Trial.
AB - The second Swedish Trial in Old patients with Hypertension (STOP-Hypertension-2)
was conducted to compare the effects of 'newer( antihypertensive therapies
(angiotensin converting enzyme [ACE] inhibitors and calcium antagonists) and
established therapies (beta-blockers and diuretics) on cardiovascular mortality
and morbidity in elderly hypertensive patients. A total of 6614 patients were
randomized to receive conventional treatment, ACE inhibitors or calcium
antagonists, and followed for a mean of 5 years. The primary endpoint was a
combination of fatal stroke, fatal myocardial infarction and other fatal
cardiovascular disease; secondary endpoints were a combination of fatal or non
fatal stroke or myocardial infarction, and other cardiovascular mortality. The
three treatments produced similar reductions in supine systolic blood pressure.
There were no significant differences in the risk of cardiovascular events
between patients receiving conventional therapy and those receiving newer
therapies. All three treatments were well tolerated. The STOP-Hypertension-2
results thus add to the extensive literature showing the benefits of blood
pressure reduction in elderly hypertensive patients. Moreover, they are
consistent with current management guidelines which emphasise the importance of
the achieved blood pressure reduction in the prevention of cardiovascular events.
PMID- 28425791
TI - Target Blood Pressure in Elderly Hypertensive Patients: How Low Should You Go?
AB - Epidemiological studies have highlighted the increasing prevalence of
hypertension with age, and the associated increase in the risk of cardiovascular
disease. A number of randomized controlled trials have shown that
antihypertensive treatment significantly reduces cardiovascular mortality and
morbidity in elderly patients, and there is evidence that the benefit achieved is
related to the extent to which blood pressure is lowered. Furthermore, a recent
analysis of data from the Hypertension Optimal Treatment (HOT) Study shows that
intensive therapy produces significantly greater reductions in blood pressure in
elderly patients than in younger patients, without increasing the risk of adverse
events. As a result, the latest management guidelines recommend that the goal of
antihypertensive therapy in elderly patients should be to achieve at least high
normal blood pressures (below 140/90 mmHg). Angiotensin II type 1 receptor
antagonists offer a new option for antihypertensive therapy in elderly patients,
and trials such as the Study on Cognition and Prognosis in the Elderly (SCOPE)
are currently investigating the effect of these agents on cardiovascular
mortality and morbidity in elderly hypertensive patients.
PMID- 28425792
TI - The Role of Ambulatory Blood Pressure Monitoring in Elderly Hypertensive
Patients.
AB - There is strong evidence that ambulatory blood pressure measurements show only
limited agreement with blood pressures measured in the clinic ('office( blood
pressures), and are more relevant to the prognosis of hypertension. Several
markers of end-organ damage, for example, have been shown to correlate more
strongly with 24-h blood pressure than with office blood pressure. In addition,
end-organ damage has been shown to be correlated with 24-h blood pressure
variability. Ambulatory blood pressure monitoring (ABPM) has revealed a number of
differences between the blood pressure profiles of elderly and younger patients.
Since 24-h blood pressure control is now widely accepted as an important goal of
antihypertensive therapy, ABPM has a potentially useful role in monitoring
treatment in clinical trials in elderly patients.
PMID- 28425793
TI - Is it Possible to Differentiate between Angiotensin II Type 1 (AT1) Receptor
Blockers in Normotensive Volunteers?
AB - Variability of blood pressure responses to inhibition of the renin-angiotensin
system is influenced by factors inherent in the patient, such as renin status,
and by drug-specific factors, such as pharmacokinetics. The pharmacokinetic
pharmacodynamic interactions of two doses of candesartan cilexetil, which is an
ester prodrug of the insurmountable angiotensin II type 1 (AT 1 ) receptor
blocker candesartan, were compared with those of the standard dose of losartan in
normotensive volunteers whose renin status was controlled by mild sodium
depletion. In a double-blind, placebo-controlled crossover study, the effects of
single oral doses of candesartan cilexetil, 8 mg and 16 mg, and losartan, 50 mg,
were compared for 24 h in 16 healthy individuals pretreated with a single 40-mg
dose of furosemide. Mean blood pressure was recorded by repeated measurements
using the oscillometric method. In addition, measurements were made of plasma
active renin, angiotensin I and angiotensin II, and plasma levels of candesartan
and EXP-3174, the active metabolites of candesartan cilexetil and losartan,
respectively, were determined by high-performance liquid chromatography and
correlated to pharmacodynamic changes. The large interindividual variability of
EXP-3174 levels in subjects who received losartan revealed a significant
correlation between active renin and peak drug levels ( r = 0.77, n = 16, p <
0.01). Such a correlation was not found within either group of individuals who
received candesartan cilexetil, because of lower interindividual pharmacokinetic
variability. A dose-response relationship was found between plasma renin and
candesartan when both doses of candesartan cilexetil were analysed. The
pharmacodynamic effects of a single oral dose of candesartan cilexetil, 16 mg,
were superior to those of candesartan cilexetil, 8 mg, and losartan, 50 mg (see
Table). This conclusion has been confirmed by the results of a parallel-group,
dose-determination study performed in hypertensive patients. The less variable
pharmacokinetic-pharmacodynamic interaction for candesartan cilexetil than for
losartan could account for the smooth 24-h reduction in blood-pressure found in
patients treated with candesartan cilexetil. These results suggest not only that
AT 1 -receptor antagonists can be differentiated, but that they will not be
equally useful in clinical practice where, in contrast to clinical research,
clear evidence is more difficult to obtain because of variability in renin
status.
PMID- 28425794
TI - Differences Among Angiotensin II Type 1 Receptor Blockers: Characteristics of
Candesartan Cilexetil.
AB - Several angiotensin II type 1 (AT 1 ) receptor blockers are now available for the
treatment of hypertension. Although the agents in this class all act by blocking
the AT 1 -receptor, they differ in their pharmacokinetics and binding
characteristics. One of the newest AT 1 -receptor blockers, candesartan
cilexetil, is administered in an inactive form and is rapidly and completely
converted to the active drug, candesartan, during gastrointestinal absorption. In
vitro studies have shown that candesartan has the highest receptor affinity of
all the available AT 1 -receptor blockers and is not displaced from the receptor
by high concentrations of angiotensin II. The tight and long-lasting binding of
candesartan to the AT 1 -receptor provides effective blockade of the negative
cardiovascular effects of angiotensin II.
PMID- 28425795
TI - Angiotensin II Type 1 Receptor Blockade: a Novel Therapeutic Concept.
AB - Angiotensin II type 1 (AT 1 ) receptor blockers, such as candesartan, are
attractive alternatives to ACE inhibitors in the treatment of hypertension and
cardiovascular disease. Although angiotensin-converting enzyme (ACE) inhibitors
are able to suppress the renin-angiotensin system (RAS), their mechanism of
action may limit their clinical utility in the treatment of hypertension. For
example, they act as competitive inhibitors of ACE. This means that their effects
can be overcome by high levels of angiotensin I, which occur after ACE inhibition
due to removal of the negative feedback effect of angiotensin II on renal renin
release. ACE inhibitors are also unable to block the production of angiotensin II
by non-ACE-mediated pathways. Furthermore, ACE is not a specific enzyme. Its
inhibition therefore has effects on other substances, such as bradykinin, leading
to the class-specific side effects associated with ACE inhibitors. Candesartan,
on the other hand, binds insurmountably to the AT 1 -receptor, thereby providing
more complete blockade of the negative cardiovascular effects of angiotensin II
than is possible with ACE inhibitors. The specificity of AT 1 -receptor blockade
also ensures that efficacy is achieved without inducing the side effect of cough
that results from the non-specific consequences of ACE inhibition. Preclinical
and early clinical studies demonstrate that AT 1 -receptor blockers produce at
least the same degree of target-organ protection as has been demonstrated for ACE
inhibitors. Additional benefits of AT 1 -receptor blockers may arise from the
fact that, unlike ACE inhibitors, they do not prevent the activity of angiotensin
II on AT 2 -receptors in the heart, which is thought to reduce cardiac
remodelling. From a mechanistic perspective, therefore, AT 1 -receptor blockers
appear to have advantages over ACE inhibitors, in terms of a more complete
blockade of angiotensin II effects, while also avoiding the specific side effects
associated with ACE inhibition.
PMID- 28425796
TI - Achieving Quality 24-h Blood Pressure Control with Candesartan Cilexetil.
AB - Epidemiological evidence suggests that optimal blood pressure control requires
strategies that lower blood pressure consistently and fully throughout 24 h. In
order to maximize compliance, antihypertensive agents also need to be well
tolerated and effective when administered at a convenient once-daily dose. The
new angiotensin II type 1 (AT 1 ) receptor blocker candesartan binds tightly to,
and dissociates slowly from, the AT1-receptor and thereby provides long-lasting
suppression of the renin-angiotensin system. This is likely to explain its
pronounced antihypertensive efficacy, which is maintained smoothly over 24 h. The
trough-to-peak ratio is a useful measure of the persistence of antihypertensive
efficacy at the end of the dosing interval. This ratio was found to be close to
the ideal of 1.0 for candesartan cilexetil, -8 and 16 mg, whereas it was 0.7 for
the prototype AT 1 -receptor blocker losartan, 50 mg. The antihypertensive effect
of candesartan cilexetil, 16 mg, was also significantly greater than that of
losartan, 100 mg, as demonstrated by ambulatory blood pressure measurements 0-36
h after dosing and by clinic measurements 48 h after dosing. By controlling blood
pressure well beyond the normal dosing interval, candesartan cilexetil provides
cardiovascular protection even in those patients who may occasionally miss doses.
PMID- 28425797
TI - Candesartan Cilexetil, 16 mg, Provides a Greater Antihypertensive Effect than
Losartan, 50 mg, in Patients with Mild to Moderate Hypertension.
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker, which binds
tightly to and dissociates slowly from the AT 1 -receptor. These binding
characteristics underpin the long duration of action and antihypertensive
efficacy of candesartan, and help to differentiate it from losartan, which was
the first AT 1 -receptor blocker to be approved for the treatment of
hypertension. This study compared the antihypertensive effect and tolerability of
candesartan cilexetil, 8 or 16 mg once daily, with that of placebo and of
losartan, 50 mg once daily, in patients with mild to moderate primary
hypertension. The dose of 50 mg for losartan was chosen, as this is the dose
usually recommended; higher doses do not seem to result in further reductions in
blood pressure. Men and women, aged 20-80 years, with primary hypertension and a
sitting diastolic blood pressure (DBP) of 95-114 mmHg at the end of a 4-week
placebo run-in period, were randomized to once-daily, double-blind treatment with
candesartan cilexetil, 8 mg ( n = 82), candesartan cilexetil, 16 mg ( n = 86),
losartan, 50 mg ( n = 84), or placebo ( n = 85) for 8 weeks. Blood pressure was
measured 6 and 24 h after dosing, i.e. at the times of peak and trough effects,
respectively. Differences among treatments in changes in blood pressure from
randomization to the end of the study were assessed by analysis of variance.
Patients were defined as having responded to treatment if sitting DBP was 90 mmHg
or below at week 8 or if sitting DBP had been reduced by more than 10 mmHg from
baseline to week 8. The proportion of responders in each treatment group was 15%
for placebo, 46% for losartan, 50 mg, 50% for candesartan cilexetil, 8 mg, and
57% for candesartan cilexetil, 16 mg. The reduction in sitting DBP at trough (the
primary effect variable) was significantly greater in patients treated with
candesartan cilexetil, 16 mg, than in patients treated with losartan, 50 mg (see
Table). In addition, both doses of candesartan cilexetil had a trough-to-peak
ratio of approximately 1.0, compared with 0.7 for losartan. Both candesartan
cilexetil and losartan were well tolerated, with the incidence of adverse events
similar to placebo in both treatment groups. Overall, the most common new-onset
adverse events reported were headache and respiratory infection, both of which
are common in this type of patient population. In conclusion, candesartan
cilexetil, 8 or 16 mg once daily, is an effective and well-tolerated
antihypertensive treatment, with a trough-to-peak ratio close to 1.0. Candesartan
cilexetil, 16 mg once daily, produces a significantly greater reduction in blood
pressure than losartan, 50 mg once daily.
PMID- 28425798
TI - Improving Antihypertensive Efficacy while Maintaining Placebo-like Tolerability.
AB - Potency and efficacy, duration of action, organ-specific effects and tolerability
are the main considerations when choosing among antihypertensive therapies.
Candesartan has been shown in in vitro animal models to bind insurmountably to
the angiotensin II type 1 (AT 1 ) receptor, thus providing effective blockade of
all the major negative cardiovascular effects of angiotensin II. Its binding
characteristics differentiate candesartan from other AT 1 -receptor blockers.
Candesartan cilexetil has been found to produce a predictable and pronounced dose
dependent decrease in blood pressure, with placebo-like tolerability even at the
highest doses studied. In comparison with the standard 50-mg dose of losartan,
candesartan cilexetil, 16 mg, was significantly more effective in suppressing the
renin-angiotensin system and in reducing trough diastolic blood pressure. Pooled
results from placebo-controlled trials also indicate that candesartan cilexetil
has equivalent efficacy to irbesartan. In addition, the extent of blood pressure
lowering by candesartan cilexetil has been shown to be similar to that of agents
in the other major classes of antihypertensive drugs, and to be effective in
combination therapy with diuretics and calcium channel blockers. Candesartan
cilexetil combines 24-h blood pressure lowering with placebo-like tolerability
and is therefore an important advance in antihypertensive therapy.
PMID- 28425799
TI - Candesartan Cilexetil, a Novel Angiotensin II Antagonist, Provides Dose-dependent
Antihypertensive Effect with Maintained Tolerability.
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker that binds
tightly to and dissociates slowly from the AT 1 -receptor. It is administered as
a prodrug, candesartan cilexetil, which is completely converted to the active
compound, candesartan, during absorption in the gastrointestinal tract. Placebo
controlled studies have shown that candesartan cilexetil is an effective
antihypertensive drug. The individual studies, however, lacked the statistical
power to assess the dose-response relationship with high precision. A more
precise estimate of the effect of different doses may be achieved by pooling
similar studies in a meta-analysis. The primary objective of this meta-analysis
was to determine the dose-response relationship for the antihypertensive effect
of candesartan cilexetil. Six European randomized, double-blind, placebo
controlled, dose-response studies with candesartan cilexetil were reported by 30
September 1996. These studies enrolled similar patients (primary hypertension
with a sitting diastolic blood pressure [DBP] of 95-114 mmHg after a placebo run
in period) and had a similar design (parallel groups and fixed doses). The doses
investigated ranged from 2 to 16 mg once daily. All doses were not given in every
study, but all studies investigated at least two different doses of candesartan
cilexetil. The duration of the double-blind phase varied between studies, but was
at least 4 weeks (range: 4-12 weeks). The variable of primary interest was
sitting DBP measured 24 h after dose (trough effect). Each dose of candesartan
was analysed separately, and compared with placebo data only from those studies
in which that dose was given. The analysis was performed using an analysis of
covariance model. Placebo-corrected estimated mean blood pressure reductions from
baseline (randomization) to the end of the study and the 95% confidence intervals
for the true mean reductions were calculated for each dose. In total, 1498
hypertensive patients were randomized, of whom 1482 provided efficacy data and
were included in the analysis. The vast majority of patients (99%) were of
Caucasian origin. The placebo-corrected reductions in sitting DBP and sitting
systolic blood pressure (SBP) achieved with the different doses of candesartan
cilexetil are shown in the Table. Reductions in blood pressure were dose-related,
and age or gender did not influence the antihypertensive effect of candesartan
cilexetil. Furthermore, blood pressure reductions achieved in the standing
position were similar to those in the sitting position, i.e. there was no
indication of an abnormal orthostatic response during treatment with candesartan
cilexetil. Heart rate was not significantly influenced by candesartan cilexetil.
Adverse events occurred in a similar proportion of patients treated with placebo
or candesartan cilexetil and did not increase with the dose. Candesartan
cilexetil was equally well tolerated in young and elderly patients and in men and
women. Thus, in European patients with mild to moderate hypertension, candesartan
cilexetil provides a clinically significant, dose-dependent, antihypertensive
effect in doses ranging from 4 to 16 mg once daily. The optimal maintenance doses
of candesartan cilexetil appear to be 8 or 16 mg once daily in most patients.
PMID- 28425800
TI - Candesartan Cilexetil is not Associated with Cough in Patients with Enalapril
induced Cough.
AB - Treatment with angiotensin-converting enzyme (ACE) inhibitors is frequently
associated with persistent dry cough. This side effect is thought to be due to
the non-specific action of ACE inhibitors, which, in addition to suppressing the
renin-angiotensin system (RAS), leads to the accumulation of kinins, encephalins
and other biologically active peptides. Candesartan cilexetil is a new, long
acting angiotensin II type 1 (AT 1 ) receptor blocker, which offers a more
specific means of suppressing the RAS than can be achieved with ACE inhibitors.
In this study, we compared the incidence and severity of cough during treatment
with candesartan cilexetil, enalapril and placebo in patients with hypertension
and enalapril-induced cough. Men and women, aged 20-80 years, with a history of
medically treated primary hypertension and ACE-inhibitor-related cough were
enrolled. The presence of cough was confirmed during a 4-week challenge period
with enalapril, 10 mg, which abated during a subsequent 4-week washout period
with placebo. Patients with confirmed ACE-inhibitor-related cough were then
randomized to double-blind treatment with candesartan cilexetil, 8 mg once daily
( n = 62), enalapril, 10 mg once daily ( n = 66), or placebo ( n = 26). Baseline
blood pressure was similar in all groups. Although blood pressure was recorded
during the study, this was for safety monitoring, and the measurements were not
standardized in relation to study drug intake or time of day. The frequency of
dry cough was recorded on a visual analogue scale (VAS). For each assessment,
patients marked a cross on a straight horizontal 100 mm line, rating cough
frequency from 'none of the time( at one end of the line to 'all of the time( at
the other end. The impact of treatment on quality of life was also studied, using
the Symptom Assessment (SA) questionnaire and the Minor Symptom Evaluation (MSE)
profile. The SA questionnaire assessed the severity of nine symptoms, including
dry cough, by means of a five-graded Likert scale (not at all, a little,
moderately, quite a bit, extremely). Changes in the three dimensions of the MSE
profile - contentment, vitality and sleep - were recorded using a VAS.
Candesartan cilexetil was superior to enalapril regarding the change in frequency
( p = 0.001) and severity ( p < 0.001) of dry cough. After 8 weeks of treatment,
the proportions of patients with cough were 26.9% for placebo, 35.5% for
candesartan cilexetil and 68.2% for enalapril ( p < 0.001, candesartan cilexetil
versus enalapril; p > 0.20, candesartan cilexetil versus placebo). Treatment with
candesartan cilexetil did not compromise patients' well-being. Compared with
placebo, candesartan cilexetil was superior in terms of its effect on
contentment; similar trends were noted for vitality and sleep, although the
differences were not significant. When all adverse events were considered,
candesartan cilexetil was very well tolerated. No serious adverse events occurred
in the candesartan cilexetil or placebo groups, while three patients in the
enalapril group reported serious adverse events (chest pain, agranulocytosis,
accidental fracture). No treatment-related changes of clinical relevance could be
found with regard to laboratory variables, ECG or vital signs/physical findings,
except the anticipated blood pressure reduction in the active treatment groups.
In conclusion, candesartan cilexetil is not associated with cough in hypertensive
patients with previous ACE-inhibitor-induced cough. The incidence of dry cough in
patients treated with candesartan cilexetil was similar to that of placebo and
lower than that of enalapril.
PMID- 28425801
TI - Efficacy and Tolerability of Candesartan Cilexetil in Special Patient Groups.
AB - Patients with hypertension do not comprise a homogeneous group, and the majority
present with a variety of concomitant and associated conditions. Antihypertensive
therapies should therefore be effective and well tolerated in a wide range of
patients and should, ideally, ameliorate the negative target-organ effects of
hypertension, such as atherosclerosis, cardiovascular remodelling and renal
impairment. Evidence is accumulating that the new angiotensin II type 1 receptor
blocker, candesartan cilexetil, lowers blood pressure effectively and is well
tolerated in a variety of patient groups, including women and the elderly. In
patients with severe hypertension, a treatment schedule based on candesartan
cilexetil, with the addition of diuretic and calcium antagonist therapy as
needed, has been found to control blood pressure successfully. Candesartan
cilexetil does not affect glucose tolerance or lipid profiles in patients with
diabetes mellitus, and it is not associated with any of the side effects of other
antihypertensive agents that would make it unsuitable for use in patients with
pulmonary disease. Initial clinical studies have indicated that candesartan
cilexetil is well tolerated and effective in patients with heart failure.
Furthermore, the available evidence shows that treatment with candesartan
cilexetil can reverse the negative effects of hypertension on left ventricular
hypertrophy and microalbuminuria. It therefore appears that the pronounced
efficacy and placebo-like tolerability of candesartan cilexetil, as demonstrated
in large clinical trials of patients with mild to moderate hypertension, can be
extended to a wide range of specific patient groups.
PMID- 28425802
TI - Candesartan Cilexetil, a Novel Angiotensin II Type 1 (AT1) Receptor Blocker,
Reduces Microalbuminuria in Patients with Type II Diabetes Mellitus and Mild
Hypertension.
AB - Microalbuminuria is a predictor of nephropathy in patients with type I or type II
diabetes mellitus, and interventions that decrease albuminuria are likely to
postpone the development of severe renal impairment. Suppression of the renin
angiotensin system by angiotensin-converting enzyme (ACE) inhibition has been
effective in this respect. However, direct inhibition of the negative
cardiovascular effects of angiotensin II by means of an angiotensin II type 1 (AT
1 ) receptor blocker would be expected to produce reductions in albuminuria
similar to those produced by ACE inhibition. In this study, we assessed the
effect of candesartan cilexetil on microalbuminuria in patients with type II
diabetes mellitus and mild hypertension. The analysis was performed in a subset
of patients ( n = 35) with microalbuminuria (10-100 mg in an overnight urine
sample) at randomization in a large double-blind, placebo-controlled study. The
subset was part of a study investigating the effect of candesartan cilexetil on
blood glucose homeostasis and the blood lipid profile in patients with stable
type II diabetes mellitus, mild hypertension (diastolic blood pressure 90-100
mmHg) and serum creatinine levels below 150 7 mol/l for men and below 120
w mol/l for women. Patients were randomized, after a 4-week placebo run-in
period, to 12 weeks of double-blind treatment with candesartan cilexetil, 8-16 mg
( n = 83), or placebo ( n = 78) once daily. After 12 weeks of treatment,
candesartan cilexetil did not influence blood glucose homeostasis or the blood
lipid profile compared with placebo. Body weight remained unchanged in both
treatment groups. Median urinary albumin excretion decreased by 57%, from 28.5 to
12.2 mg/12 h, in patients treated with candesartan cilexetil ( n = 15), whereas
it increased by 9%, from 30.2 to 32.8 mg/12 h, in the placebo group ( n = 20; p =
0.03 for the difference between treatments). The mean reduction in diastolic
blood pressure was 6.4 mmHg in the group given candesartan cilexetil and 3.6 mmHg
in the group given placebo. In conclusion, 12 weeks of treatment with the AT 1
receptor antagonist candesartan cilexetil reduced microalbuminuria in patients
with stable type II diabetes mellitus and mild hypertension. Thus, candesartan
cilexetil appears to have the potential for renal protection in this patient
category.
PMID- 28425803
TI - Improving Prognosis in Hypertension: Exploring the Benefits of Angiotensin II
Type 1 Receptor Blockade.
AB - Prognosis can be improved in hypertensive patients not only by reducing blood
pressure, but probably also by effective suppression of adverse neurohormonal
influences. Inhibition of the renin-angiotensin system by angiotensin-converting
enzyme inhibitors effectively reduces left ventricular hypertrophy and decreases
morbidity and mortality due to heart failure, as well as slowing the progression
of renal disease. Initial data from studies of angiotensin II type 1 (AT 1 )
receptor blockers indicate that these agents should also be effective in reducing
cardiac and renal damage. In this class, candesartan, by virtue of its tight and
long-lasting binding to the AT 1 -receptor, provides pronounced 24-h blood
pressure control with effective blockade of all the major negative cardiovascular
effects of angiotensin II. Candesartan cilexetil has also been shown to be
effective and well tolerated in combination with hydrochlorothiazide in those
hypertensive patients who require more than one agent to reach their target blood
pressure.
PMID- 28425804
TI - Reducing Cardiovascular Morbidity and Mortality in the Elderly.
AB - Candesartan cilexetil is highly effective at lowering blood pressure, whilst
maintaining placebo-like tolerability, in a wide range of patient groups.
Although the benefit of lowering blood pressure in elderly patients with moderate
hypertension has been demonstrated in several large-scale clinical trials,
elderly patients with mild hypertension have rarely been studied. The high
incidence of cardiovascular and cerebrovascular mortality and morbidity,
including dementia, in the elderly means that control of blood pressure is
particularly important in this patient group. A major new international clinical
trial - SCOPE (Study on COgnition and Prognosis in the Elderly) - has therefore
been initiated. This is a prospective, randomized, double-blind, parallel
comparison of the effects of candesartan cilexetil, 8 or 16 mg once daily, and
placebo in about 5000 patients who will be followed for a mean of 2.5 years.
SCOPE is the first study designed to assess the effect of antihypertensive
therapy in elderly patients (70-89 years of age) with mild hypertension (sitting
systolic blood pressure of 160-179 mmHg and/or sitting diastolic blood pressure
of 90-99 mmHg). The primary objective of the study is to determine the effect of
candesartan cilexetil on major cardiovascular events (cardiovascular death, non
fatal stroke and myocardial infarction, and silent myocardial infarction), while
an important secondary objective is to determine the effect of such treatment on
the prevention of cognitive impairment. SCOPE should provide definitive evidence
of the cardiovascular and cerebrovascular benefits of treating mildly
hypertensive elderly patients with angiotensin II type 1 receptor blockers, which
not only reduce blood pressure, but may also provide significant protection from
the negative effects of angiotensin II on target organs.
PMID- 28425805
TI - Study on COgnition and Prognosis in the Elderly (SCOPE): Design and Objectives.
AB - Hypertension is a major risk factor for cardiovascular events, including stroke,
as well as for white matter lesions of the brain. There is also evidence to link
cognitive impairment and dementia to hypertension. However, it has not been
established whether antihypertensive treatment of elderly patients with a
diastolic blood pressure (DBP) in the range 90-99 mmHg provides protection
against major cardiovascular events and cognitive impairment. The Study on
COgnition and Prognosis in the Elderly (SCOPE) is the first study designed to
assess the effects of antihypertensive drug treatment on major cardiovascular
events and cognitive function in elderly patients with mild hypertension. SCOPE
is a prospective, randomized, double-blind, parallel comparison of the effects of
the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil and
placebo on major cardiovascular events (myocardial infarction [MI], stroke and
cardiovascular death), cognitive function as measured by the Mini-Mental State
Examination (MMSE), quality of life (QoL) and health economics. The study has
included both men and women, aged 70-89 years of age, with systolic blood
pressure (SBP) of 160-179 mmHg and/or DBP of 90-99 mmHg and an MMSE score of 24
or above. Nearly 5000 patients have been recruited and will be followed for a
mean period of 2.5 years. After a run-in period of 1-3 months, patients were
randomized to receive placebo or candesartan cilexetil, 8 mg once daily, which
has been shown to provide effective and long-lasting blood pressure reductions,
while maintaining placebo-like tolerability, in elderly patients. All previous
antihypertensive treatment was standardized to hydrochlorothiazide (HCTZ), 12.5
mg, at enrolment. At any time during the study, the dose of study drug will be
doubled if SBP rises above 160 mmHg or DBP rises above 85 mmHg. If an SBP above
160 mmHg or a DBP above 90 mmHg is observed despite the increase in study
medication, additional antihypertensive medication with HCTZ is recommended.
Assessments to be made during the study will include blood pressure, heart rate,
ECG, MMSE, health economics and QoL. Data on adverse events and clinical events
will also be collected throughout the study. SCOPE is organized and co-ordinated
by an Executive Committee, a Steering Committee, an Independent Safety Committee,
an Independent Event Committee and a Co-ordinating Centre. Countries
participating in the Study include Belgium, Canada, Finland, France, Germany, UK,
Hungary, Israel, Norway, Poland, Portugal, Spain, Sweden, The Netherlands and the
USA. Inclusion of patients was completed in January 1999 and at that time 4964
patients were randomized. The baseline characteristics of these patients are
shown in the Table.
PMID- 28425806
TI - Preserving Target-organ Function with Candesartan Cilexetil in Patients with
Hypertension.
AB - Epidemiological evidence suggests that reducing blood pressure alone in
hypertensive patients delays the onset of cardiovascular events without
necessarily preventing the progression of chronic target-organ disease, such as
end-stage renal failure and heart failure. Successful clinical management of
hypertensive patients will therefore not be possible unless therapies are aimed
both at the effective control of blood pressure and at the preservation of target
organ function. The new angiotensin II type 1 (AT 1 ) receptor blocker
candesartan cilexetil has been shown to be effective in reducing target-organ
damage in animal models of hypertension, even at doses that do not produce
significant reductions in blood pressure. Protective effects of candesartan
cilexetil towards the heart and kidney have also been demonstrated in the
clinical studies that have been conducted to date. Thus, candesartan cilexetil
has been shown to induce regression of left ventricular hypertrophy within 8-12
weeks of treatment and to improve renal haemodynamics, both acutely and after 6
weeks of treatment in hypertensive patients. Furthermore, in hypertensive
patients with co-existent non-insulin-dependent diabetes mellitus and
microalbuminuria, 12 weeks of treatment with candesartan cilexetil, 8-16 mg,
significantly reduced urinary albumin excretion. Clinical evidence is therefore
accumulating that the antihypertensive efficacy and tolerability profile already
established for candesartan cilexetil is combined with the renal and
cardioprotective effects necessary for optimal management of hypertension.
PMID- 28425807
TI - Antihypertensive Effects and Tolerability of Candesartan Cilexetil in an Elderly
Population.
AB - The pharmacokinetics and pharmacodynamics of antihypertensive drugs are often
influenced by age, and may be different in elderly and younger patients. The
choice of drug and dosage in the elderly therefore merits special consideration.
The aim of this placebo-controlled study was to determine the efficacy and
tolerability of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan
cilexetil with placebo in elderly patients with primary hypertension. Men and
women, aged 65 years or older and with supine diastolic blood pressure (DBP) of
95-114 mmHg, were randomized to double-blind, once-daily treatment with
candesartan cilexetil, 8 mg ( n = 96), or placebo ( n = 97) for 12 weeks. The
dose was increased to 16 mg once daily if DBP was greater than 90 mmHg after 6
weeks of treatment. Forty-nine per cent of the patients remained on the 8 mg
dose. At each visit, systolic blood pressure (SBP) and DBP were measured 24 h
after dosing. After the first dose following randomization, blood pressure was
also measured at 2 and 4 h. Placebo-corrected changes in supine blood pressure
with candesartan cilexetil are shown in the Table. At the end of the study, the
mean reductions in placebo-corrected supine DBP and SBP in patients receiving
candesartan cilexetil were 7.5 mmHg and 13.6 mmHg, respectively ( p < 0.001 vs
placebo). The incidence of adverse events in this treatment group was similar to
that in the placebo group. Only four patients in the candesartan cilexetil group
withdrew due to adverse events, compared with ten in the placebo group. There was
no evidence of an orthostatic effect. In conclusion, in elderly hypertensive
patients, candesartan cilexetil, 8-16 mg once daily, is an effective and well
tolerated antihypertensive treatment, which has a smooth onset of action and no
exaggerated response after the first dose.
PMID- 28425808
TI - The Renin-Angiotensin System and Cardiovascular Disease.
AB - Suppression of the renin-angiotensin system (RAS) with angiotensin-converting
enzyme (ACE) inhibitors is an established method for controlling blood pressure
and reducing the risk of cardiovascular disease. In addition to reducing blood
pressure, suppression of the RAS is able to protect against the target-organ
damage that results from hypertension. Unfortunately, despite the use of ACE
inhibitors and agents from the other classes of conventional antihypertensives,
effective control of blood pressure remains poor. A major contribution to this
failure to control blood pressure appears to be lack of compliance with the
prescribed medication, arising from the presence of unacceptable side effects.
Angiotensin II type 1 (AT 1 ) receptor blockers, such as candesartan, are the
latest class of antihypertensive agent to be developed. They target the AT 1
receptor - the final common pathway for all the known negative cardiovascular
effects of angiotensin II - and provide pronounced antihypertensive efficacy
without the side effects of cough and angioneurotic oedema that are associated
with the use of ACE inhibitors.
PMID- 28425809
TI - A Combination of Candesartan Cilexetil/hydrochlorothiazide (HCTZ), 8/12.5 mg, has
a Similar Antihypertensive Efficacy and is Better Tolerated than Lisinopril/HCTZ,
10/12.5 mg.
AB - Monotherapy with an antihypertensive agent is likely to achieve a desirable
lowering of blood pressure in about 50% of patients. The remaining proportion of
patients are likely to be only partially responsive or unresponsive, even if
appropriate dose adjustments are made. For these patients, combination therapy
usually leads to better control of hypertension. The aim of this study was to
compare the antihypertensive effect and tolerability of a once-daily combination
of the angiotensin II type 1 (AT 1 ) receptor blocker candesartan cilexetil, 8
mg, and the diuretic hydrochlorothiazide (HCTZ), 12.5 mg, with a combination of
the angiotensin-converting enzyme inhibitor, lisinopril, 10 mg, and HCTZ, 12.5
mg, in patients with primary hypertension. The study included men and women, 20
80 years of age, with sitting diastolic blood pressure (DBP) of 95-114 mm Hg.
After a run-in period of 2 weeks on any antihypertensive monotherapy, 355
patients were randomized to double-blind treatment with either a combination of
candesartan cilexetil/HCTZ, 8/12.5 mg, or a combination of lisinopril/HCTZ,
10/12.5 mg, for 26 weeks. Blood pressure was measured 24 h after dose intake, the
primary efficacy variable being the change in sitting DBP at trough between
baseline and 26 weeks of treatment. Reductions in mean sitting DBP after 26 weeks
were similar for both combination treatments. In addition, no differences were
found between the two treatment groups regarding standing DBP, sitting and
standing systolic blood pressure, heart rate, and the proportion of responders
and controlled patients. Significantly fewer patients reported at least one
adverse event with candesartan cilexetil/HCTZ than with lisinopril/HCTZ (68.9% vs
79.5%, p = 0.02; see Table). Furthermore, the proportion of patients
spontaneously reporting cough was markedly higher in the lisinopril/HCTZ group
(23.9%) than in the candesartan cilexetil/HCTZ group (5.0%). Thus, although the
combinations of candesartan cilexetil/HCTZ, 8/12.5 mg once daily, and
lisinopril/HCTZ, 10/12.5 mg once daily, had similar antihypertensive efficacy in
patients with mild to moderate hypertension during the 26-week treatment period,
candesartan cilexetil/HCTZ was significantly better tolerated than
lisinopril/HCTZ.
PMID- 28425810
TI - Candesartan, an Insurmountable Antagonist of Angiotensin II-mediated Contractile
Effects in Isolated Vascular Preparations: Comparison with Irbesartan, Losartan
and its Active Metabolite (EXP-3174).
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker that produces
more effective 24-h blood pressure lowering than losartan in hypertensive
patients. In in vitro tissue preparations, candesartan displays insurmountable
antagonism of the responses to angiotensin II. Both irbesartan and EXP-3174, the
active metabolite of losartan, have also previously been described in some
studies as insurmountable AT 1 -receptor blockers, whereas losartan exhibits
surmountable blockade of the AT 1 -receptor. We compared the properties of
candesartan, irbesartan, losartan and EXP-3174 in isolated vascular preparations
of rat portal vein and rabbit aortic strips. The concentrations of the different
AT 1 -receptor antagonists that were effective in these in vitro preparations
were also correlated to the non-protein bound plasma concentrations obtained in
clinical use. Preparations of the rabbit aorta and the rat portal vein were
dissected, mounted on a force-displacement transducer and submerged in oxygenated
Krebs' buffer at 37 degrees C. The vessel strips were pre-stretched to a passive
force of 5 and 20 mN for portal vein and aorta, respectively. The response to
angiotensin II, measured as the mean force development in response to increasing
concentrations of angiotensin II, was recorded in the absence and presence of
candesartan, 0.003-10 nmol/l, irbesartan, 1-100 nmol/l, losartan, 1-100 nmol/l,
and EXP-3174, 0.01-10 nmol/l, for a period of 90 min. In rabbit aortic strips,
candesartan caused a non-parallel shift and suppression of the angiotensin II
concentration-response curve, with complete suppression of the response to
angiotensin II at a dose of candesartan of 1 nmol/l. In contrast, irbesartan,
losartan and EXP-3174 all caused a parallel shift of the concentration-response
curve. No suppression of the angiotensin II response was seen with losartan,
while its active metabolite caused saturable suppression of the maximal response
at higher concentrations. For irbesartan, some degree of suppression of the
maximal response could not be excluded at the highest concentration studied.
Similar concentration-response curves were obtained in rat portal vein. Data on
protein binding for the different AT 1 -receptor blockers are variable in the
literature. Plasma protein binding for the different AT 1 -receptor blockers was
determined (in triplicate) by liquid chromatography with fluorescence detection
after equilibrium dialysis (6 h) of cold drug at a concentration of 1500 nmol/l.
Protein binding was high (see Table) and, for candesartan, losartan and its
active metabolite EXP-3174, in accordance with previously reported levels. For
irbesartan, a large discrepancy in protein binding between previously reported
and the present experimental data, obtained from two different non-associated
laboratories, was found. The higher plasma protein binding for irbesartan found
in the present study may explain why high doses of irbesartan seem to be needed
for clinical efficacy. It appears unlikely that losartan exerts any significant
inhibitory effect at therapeutic plasma levels, and the main AT 1 -blocking
effect observed after oral losartan is probably exerted by EXP-3174. It is
concluded that AT 1 -receptor blockers differ in their ability to inhibit
angiotensin II-mediated vascular contraction, and that the antagonistic
characteristics are similar in vessel preparations of different origins and with
different degrees of AT 1 -receptor reserve.
PMID- 28425811
TI - Candesartan Causes Long-lasting Antagonism of the Angiotensin II Receptor
mediated Contractile Effects in Isolated Vascular Preparations: a Comparison with
Irbesartan, Losartan and its Active Metabolite (EXP-3174).
AB - Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker. It displays
insurmountable antagonism of angiotensin II responses, binding tightly to and
dissociating slowly from the AT 1 -receptor. The purpose of this study was to
compare the duration of angiotensin II antagonism by the AT 1 -receptor blockers
candesartan, irbesartan, losartan and its active metabolite EXP-3174 in an
isolated tissue preparation. The contractile response to angiotensin II was
studied in the isolated portal vein of the rat, during incubation with AT1
receptor blockers and after an extensive washout period. The portal vein
preparation was pre-stretched to a passive force of 5 mN in an organ bath filled
with oxygenated Krebs' buffer at 37 degrees C. The contractile tension developed
by the vascular smooth muscles was monitored using a force-displacement
transducer. The contractile response to repeated administration of angiotensin II
was recorded before, during and following exposure (for 30-180 min) to
candesartan, 0.1-1 nmol/l, irbesartan, 1-50 nmol/l, losartan, 30-100 nmol/l, and
EXP-3174, 1-10 nmol/l. Drug exposure was followed by washing for up to 2 h.
Candesartan produced a long-lasting blockade of the vascular contractile response
to angiotensin II, as shown by maintenance of inhibition during the washout
period. This effect of candesartan was independent of drug concentration and
exposure time prior to washing. Irbesartan, losartan and EXP-3174 also blocked
the angiotensin II-mediated contraction. However, in contrast to candesartan, the
responses to angiotensin II rapidly returned towards baseline values during the
washout period. The relatively short-lasting blockade by irbesartan, losartan and
EXP-3174 was also independent of drug concentration and exposure time prior to
washout. It is concluded that the AT 1 -receptor blockers differ in their ability
to inhibit angiotensin II-mediated vascular contraction, with candesartan
producing longer-lasting blockade than irbesartan, losartan and EXP-3174. The
mechanism of the persistent inhibitory effect of candesartan is at present
unclear. Possible explanations include tight binding and slow dissociation from
the AT 1 -receptor, tissue accumulation resulting in 'local( dissociation and
reassociation to the AT 1 -receptor, and stimulation of internalization of the AT
1 -receptor.
PMID- 28425812
TI - Exploring New Treatment Strategies in Heart Failure.
AB - Heart failure remains a major and increasing cause of mortality and morbidity,
even when the best available treatments are used. One of its key causes is
neuroendocrine activation via the sympathetic nervous system and the renin
angiotensin system (RAS). Neuroendocrine blockers of the sympathetic nervous
system (beta-blockers) and of the RAS (angiotensin-converting enzyme [ACE]
inhibitors and angiotensin II type 1 [AT 1 ] receptor blockers) therefore have an
important potential therapeutic role in heart failure. The promising results from
clinical trials with beta-blockers suggest that these drugs will become an
established part of the future management of patients with mild to moderate
symptomatic heart failure. Blockade of the RAS with ACE inhibitors has also been
shown to be effective in reducing the risk of morbidity and mortality in patients
with heart failure. Blockade of the AT1-receptor, with agents such as
candesartan, produces more specific and, theoretically, more complete blockade of
the major negative cardiovascular effects of angiotensin II than is possible
using ACE inhibitors, whilst maintaining placebo-like tolerability. Furthermore,
AT 1 -receptor blockade leads to increased stimulation of the angiotensin II type
2 (AT 2 ) receptor, which, according to experimental data, may have favourable
cardiovascular effects. Following encouraging results from two pilot studies, a
major new international study programme - CHARM (Candesartan in Heart failure -
Assessment of Reduction in Mortality and morbidity) - has been initiated to
define the clinical benefits of candesartan cilexetil in a wide variety of
patients with symptomatic heart failure. CHARM is the first study to accept all
relevant heart failure patients who may benefit from RAS blockade, irrespective
of their left ventricular function or tolerance of ACE inhibitors. The 6500
patients to be recruited will be divided among three integrated outcome studies.
Two of these studies will examine the effect of candesartan cilexetil versus
placebo in patients with an ejection fraction of 40% or less who are tolerant or
intolerant of ACE inhibitors. The third study arm will examine the benefits of
candesartan cilexetil in a previously seldom studied group: those with
symptomatic heart failure, but with preserved left-ventricular systolic function.
Recruitment of patients into the study has started.
PMID- 28425813
TI - Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity
(CHARM) Study Programme.
AB - Heart failure is a major cause of death, hospital admissions and poor quality of
life. It affects some 1-2% of the general population, increasing to up to 8% in
people over 75 years of age. Although treatment with angiotensin-converting
enzyme (ACE) inhibitors reduces symptoms and mortality, 50-70% of patients with
heart failure still die within 5 years of diagnosis. There is thus clear scope
for improving the treatment of patients with this condition. The CHARM programme
is designed to define the clinical benefits of the long-acting angiotensin II
type 1 (AT 1 ) receptor blocker, candesartan cilexetil, in a wide variety of
patients with symptomatic heart failure. Candesartan cilexetil will be evaluated
in three double-blind, randomized studies involving patients grouped according to
left ventricular function and ACE inhibitor tolerance/intolerance.
PMID- 28425814
TI - Verbal short-term memory and language impairments in Cantonese speakers after
stroke.
AB - PURPOSE: The study examined the relationship between verbal short-term memory
(STM) and language impairment in Cantonese speakers after stroke. It is
hypothesised that Cantonese speakers with left-hemisphere (LH) stroke would
perform worse than those with right hemisphere (RH) stroke and normal controls.
Specific linguistic factors of Cantonese might affect results in the tasks.
METHOD: Fifteen participants with LH stroke, 10 with RH stroke and 25 healthy
controls were tested with auditory-verbal immediate serial recall (ISR) tasks and
auditory linguistic tasks. All stroke participants were assessed with the
Cantonese version of Western Aphasia Battery (CAB). RESULT: The LH group
performed significantly worse than the RH and healthy control groups in the
auditory verbal ISR and auditory linguistic tasks. There were significant
lexicality, frequency and imageability effects in most tasks. Auditory
discrimination and word comprehension tasks, but not the auditory word
recognition task had correlations with ISR tasks. CONCLUSION: Verbal STM and
language performance of Cantonese-speakers with history of LH stroke were
inferior to RH stroke and healthy controls. The effects of lexicality, word
frequency and imageability on verbal STM memory performance were found. Cantonese
tones have effects on performance in auditory word recognition task, similar to
onset, nucleus and rime.
PMID- 28425818
TI - Immunization with 10-valent pneumococcal non-typeable Haemophilus influenzae
protein D conjugate vaccine (PHiD-CV) according to different schedules in infants
in South Africa: a phase III trial.
AB - BACKGROUND: Limited clinical data exists to assess differences between various
infant pneumococcal conjugate vaccine schedules. In this trial, we evaluated
immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae
protein D conjugate vaccine (PHiD-CV) administered using 3 different immunization
schedules in HIV unexposed-uninfected infants in South Africa. METHODS: In this
phase III, open, single-center, controlled study (clinicaltrials.gov:
NCT00829010), 300 infants were randomized (1:1:1) to 1 of 3 PHiD-CV schedules: 3
dose priming and booster (3 + 1); 3-dose priming without booster (3 + 0); or 2
dose priming and booster (2 + 1). The booster was administered at 9-10 months of
age. immune responses were assessed up to 21 months after primary vaccination.
RESULTS: Post-priming antibody levels tended to be lower in the 2 + 1 group. At 6
months post-priming, antibody concentrations and opsonophagocytic activity titers
were within similar ranges after 2- or 3-dose priming. Robust increases were
observed pre- to post-booster in the 3 + 1 and 2 + 1 groups. CONCLUSIONS: PHiD-CV
was immunogenic when administered in different schedules. Post-booster responses
suggest effective immunological priming with both 2- and 3-dose primary series
and support administration of the booster dose at 9-10 months of age.
PMID- 28425819
TI - Early intervention in multiple sclerosis: how can we maximise patient prospects?
PMID- 28425820
TI - Metastatic soft tissue sarcoma: current treatment landscape and future
perspectives.
AB - INTRODUCTION: The therapeutic armamentarium for advanced soft tissue sarcoma
(STS) has increased over the last few years. Doxorubicin monotherapy or in
combination is now the established first line treatment. Beyond first line
treatment, no standard therapy has been established. Novel drugs have reached the
late-clinical stage development demonstrating to be effective in controlled
studies. While these novel treatments can be beneficial to a subset of patients,
even producing long lasting remissions, a significant fraction of the STS
population derives limited benefit. This is due to the fact that STS is a very
heterogeneous disease with different histopathologic features, biological
characteristics and clinical behaviour. Areas covered: The primary aim of this
review is to summarize data from recent phase III clinical trials in unselected
STS population, and to discuss their impact on the current clinical practice.
Phase I-II trials of special interest are discussed as well. Expert commentary:
Although our efforts in this research task are ongoing, the integration of
biological therapies, the anti-angiogenesis targeted treatments as well as
immunotherapy that may further improve the long term control of advanced STS are
of special clinical interest. Clinical management of advanced STS should be
tailored to each patient in order to optimize therapy.
PMID- 28425821
TI - L-Carnitine supplementation to reverse hyperammonemia in a patient undergoing
chronic valproic acid treatment: A case report.
AB - Valproic acid is a broad-spectrum anticonvulsant that has also gained attention
in the psychiatric setting. With respect to safety, valproic acid may induce a
seemingly rare condition, hyperammonemia, which can induce a wide variety of
symptoms ranging from irritability to coma. The proposed mechanism of
hyperammonemia involves depletion of carnitine and overproduction of a toxic
metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus
ammonia elimination. Carnitine is a commonly used antidote for acute intoxication
of valproic acid, but is not a therapeutic option for management of chronic
adults with adverse effects related to valproic acid. We herein report a case
involving a woman with epilepsy who developed hyperammonemia after a change in
her anticonvulsant therapy. She reported increased seizures and gastrointestinal
disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine
levels were monitored. Her ammonia level was elevated and her carnitine level was
at the inferior limit of the population range. She was supplemented with
carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine
level increased, and her seizures were better controlled. Carnitine
supplementation was useful for reversal of her hyperammonemia, allowing her to
continue valproic acid for seizure control.
PMID- 28425822
TI - Association of hepatic vein Lipiodol tram-track sign during transcatheter
arterial chemoembolization with perioperative death.
AB - Objective To assess the relationship between the hepatic vein Lipiodol tram-track
sign during transcatheter arterial chemoembolization (TACE) and perioperative
death. Methods Patients treated for hepatic carcinoma at the Beijing Shijitan
Hospital, Capital Medical University from January 2010 to December 2015 were
retrospectively evaluated. The patients underwent hepatic TACE with Lipiodol. The
incidence of the hepatic vein Lipiodol tram-track sign, prognosis, and possible
risk factors were analyzed. Results A total of 5372 patients underwent hepatic
TACE and had complete available intraoperative imaging data. Among them, nine
patients showed the hepatic vein Lipiodol tram-track sign, including five who
died intraoperatively. The patients who died had liver metastasis from
hepatocellular carcinoma, cholangiocarcinoma, or breast cancer and had previously
received doxorubicin. The survivors had metastasis from gastric or colorectal
cancer and had not received doxorubicin. Conclusion Occurrence of the hepatic
vein Lipiodol tram-track sign during hepatic TACE is likely to result in
perioperative death.
PMID- 28425823
TI - Association between sleep time and depression: a cross-sectional study from
countries in rural Northeastern China.
AB - Objective To investigate the current situation of sleep status and examine its
association with depression among counties in rural areas of Liaoning Province,
China. Methods This cross-sectional study was conducted from January 2012 to
August 2013 in Northeast China. A total of 11,276 subjects aged >=35 years were
surveyed and completed the Patient Health Questionnaire-9; each participant
answered questions about their sleep duration. Results For individuals with a
sleep time of <=6, 6-7, 7-8, 8-9, and >=9 h, the respective risk of depression
was 10.8%, 3.7%, 2.6%, 2.7%, and 5.7% in subjects younger than 65 years old and
15.2%, 5.4%, 3.2%, 6.5%, and 8.6% in those 65 years old or older. Conclusion In
the rural population of Liaoning Province, sleep duration and depression are
closely related. Both short sleep and long sleep are risk factors for depression.
Optimizing sleep status may contribute to good physical and mental health.
PMID- 28425824
TI - Isolated ACL versus multiple knee ligament injury: associations with patient
characteristics, cartilage status, and meniscal tears identified during ACL
reconstruction.
AB - OBJECTIVES: The objectives of this study were to determine (1) if patients
undergoing reconstruction of an isolated anterior cruciate ligament (ACL) tear
had different characteristics (age, gender, body mass index [BMI]) than patients
undergoing ACL reconstruction (ACLR) with multiple knee ligament (MKL) tears and
(2) whether there was a difference in prevalence of articular cartilage injury
and meniscus tears between these two groups. METHODS: Patients undergoing primary
ACLR between February 2005 and June 2013 were identified through an ACLR
registry. Patients were grouped by whether they had an isolated ACL tear or an
ACL tear associated with another knee ligament tear. The study cohort was
analyzed to identify differences in patient characteristics and
cartilage/meniscus injury patterns between the groups. RESULTS: Of the 21,377
ACLR cases enrolled in the registry during the study period, 2.5% (n = 549) had
MKL tears. The MKL group had more males (73.2% vs. 62.8%, p < 0.001) than the
isolated ACL group. The MKL group also had a higher percentage of patients with a
BMI greater than 30 (31.1% vs. 22.7%, p = 0.0002). When adjusting for these
variables, any articular cartilage injury was equal in the two groups (OR = 1.01,
CI 0.82-1.25, p = 0.922), while medial femoral condyle injury was less common in
the MKL group (OR = 0.73, CI = 0.56-0.07, p = 0.28). The likelihood of any
meniscus tear was lower in the MKL group (OR = 0.56, CI = 0.47-0.67, p < 0.001)
as was the likelihood of medial meniscus tears (OR = 0.53, CI = 0.44-0.65, p <
0.001). CONCLUSIONS: When comparing patients with MKL tears versus isolated ACL
tears at ACLR, there was a higher percentage of males and patients with BMI over
30 in the MKL group. Medial femoral condyle articular cartilage injury, any
meniscus tear, and medial meniscus tears were less common in patients with MKL
injury compared to patients with isolated ACL tears.
PMID- 28425825
TI - Reviewing treatments and outcomes in the evolving landscape of ulcerative
colitis.
AB - Ulcerative colitis (UC) is a chronic inflammatory disease extending proximally
from the rectum to varying lengths of the colon that is characterized by
alternating cycles of relapse and remission. Therapeutic goals for patients with
active UC include induction and maintenance of remission and improvement in
quality of life, as well as mucosal healing, a clinical outcome recently
recognized in treatment guidance as being equally important. Mucosal healing is
associated with favorable long-term patient outcomes related to remission,
surgery, hospitalization, and quality of life. Given the increasing number of
newer therapies available, it is important to properly position the use of each
agent within the landscape of established UC therapies, evolving therapeutic
goals, and established guidelines. Extent of disease is important to consider
when selecting a treatment, as is an understanding of the short- and long-term
outcomes (e.g. corticosteroid-free remission, mucosal healing) associated with
each treatment. The purpose of this narrative review is to provide an overview of
newer therapies for the treatment of UC and how they may best fit in the evolving
landscape of UC.
PMID- 28425826
TI - Lung function and prevalence of respiratory symptoms in Norwegian crab processing
workers.
AB - BACKGROUND: Seafood processing workers have an increased risk of developing
occupational asthma. This has not been studied among Norwegian crab processing
workers, nor has the respiratory health of exposed workers been compared to a
control group. OBJECTIVES: Assessing the impact of working in the crab processing
industry on workers' respiratory health. DESIGN: A cross-sectional study of the
respiratory health in two types of crab processing workers compared to a control
group. METHODS: The study included 148 king crab (Paralithodes camtschaticus)
workers, 70 edible crab (Cancer pagurus) workers and 215 controls. Workers
answered a questionnaire and performed spirometry measurements. chi2 and Fishers
exact tests were performed on self-reported respiratory symptoms. Regression
analyses and t-tests were used to assess lung function values. RESULTS: Self
reported respiratory symptoms were higher among crab processing workers compared
to controls, and higher among king crab workers compared to edible crab workers.
There was no significant difference between crab processing workers and controls
in lung function measurements. Self-reported doctor-diagnosed asthma prevalence
was highest in the control group. CONCLUSIONS: Increased respiratory symptoms
reported by crab processing workers were not reflected in impaired lung function
values or asthma diagnose. We suggest a healthy worker effect among crab
processing workers in Norway.
PMID- 28425827
TI - Efficacy of glycine powder air-polishing combined with scaling and root planing
in the treatment of periodontitis and halitosis: A randomised clinical study.
AB - Introduction This study was performed to evaluate the clinical efficacy of using
the Perio-Flow device (Electro Medical Systems, Nyon, Switzerland) adjunctively
with mechanical instrumentation on periodontal parameters and halitosis.
Materials and Methods Sixty patients who presented with a 4- to 6-mm probing
pocket depth were recruited for the study. Patients were randomly assigned to
scaling and root planing (SRP) or SRP + glycine powder air-polishing (GPAP). For
both groups, the plaque index, gingival index, pocket depth, bleeding on probing,
and clinical attachment level scores were recorded at baseline and 1 month.
Volatile sulphur compounds (VSCs) were measured by a Halimeter (Interscan Corp.,
Chatsworth, CA, USA) at baseline, immediately after treatment, and at 7, 14, and
30 days. Results Both groups showed significantly lower plaque index, gingival
index, pocket depth, bleeding on probing, and clinical attachment level gain
scores at 1 month than at baseline. No significant differences were found between
the groups at any time point. The VSCs were significantly different at 1 month
compared with baseline in both groups. However, the intergroup comparisons of
VSCs were not statistically significant at any time point. Conclusion Within the
limits of this study, SRP is effective for treatment of periodontitis and
halitosis. However, using GPAP adjunctively with mechanical instrumentation has
no beneficial effects on halitosis or periodontal parameters.
PMID- 28425828
TI - Compliance to guidelines for the prescribing of antibiotics in acute infections
at Namibia's national referral hospital: a pilot study and the implications.
AB - BACKGROUND: Sub-optimal antibiotic prescribing remains a public health concern in
Namibia. The objective was to determine the level and predictors of compliance to
guidelines in the prescribing of antibiotics in acute infections at a national
referral hospital in Namibia to improve future prescribing. METHODS: An
analytical cross-sectional survey design. The clinical records of patients
receiving care were reviewed. Prescribing practices were assessed using a self-
administered questionnaire with reference to Namibia Standard Treatment
Guidelines (NSTG). RESULTS: The majority of prescriptions (62%) complied with the
NSTGs; however, lower than national targets (95%). Most prescriptions were
empiric and prescribers typically made reference to the NSTG (58%). Diagnosed
infections were principally respiratory infections (58%) and penicillins were the
most used antibiotics. Good concurrence between signs and symptoms with the
diagnosis indicated on the prescription - OR=5.2 (95% CI: 1.4, 19.2), a diagnosis
of upper respiratory tract (p=0.001), oral-dental OR=0.1(95% CI: 0.03,0.3) and
urogenital infections OR=0.3(95% CI: 0.1,0.95) and the prescribing of penicillins
(p=0.001) or combination antibiotics and amphenicols were independent predictors
of compliance to the NSTGs. The main behaviours associated with antibiotic
prescribing were patient influences, clinical state, and access to guidelines.
CONCLUSIONS: Compliance with NSTGs is suboptimal. Prescribing of combination
antibiotics, penicillins and diagnosis of oral dental, genitourinary and ear,
nose and throat infections were important predictors for NSTG compliance. There
is a need to implement antibiotic indicators and stewardship programmes, and
ensure access to NSTGs, to improve future antibiotic prescribing in Namibia.
PMID- 28425830
TI - Tryptase inhibitors: a patent review.
AB - INTRODUCTION: Tryptase is one of the main serine-proteinases located in the
secretory granules of mast cells, and is released through degranulation, which is
involved in the pathogenesis of allergic inflammatory disease, cardiovascular
diseases, lung fibrosis and tumor. Therefore, inhibitors targeting tryptase may
represent a new direction for the treatment of allergic inflammatory disease and
other diseases. Areas covered: In this article, we discussed the history and
development of tryptase inhibitors and described a variety of tryptase inhibitors
via their structures and biological importance in clinical studies and drug
development for tryptase-related diseases. Expert opinion: Initial tryptase
inhibitors based on indole structure as the hydrophobic substituent on a
benzylamine-piperidine template have low specificity and poor bioavailability.
Therefore, designing new and specific inhibitors targeting tryptase should be
involved in future clinical studies. Modifications toward indoles with varying N
substitution, introducing an amide bond, and growing the chain length contribute
to an increase in the specific selectivity and potency of tryptase inhibitors.
Tryptase has become the research hotspot to explore many related diseases.
Therefore, there has been growing appreciation for the potential importance of
the tryptase inhibitors as a target for treating these diseases.
PMID- 28425829
TI - Effects of dexmedetomidine versus midazolam for premedication in paediatric
anaesthesia with sevoflurane: A meta-analysis.
AB - Background Dexmedetomidine (DEX), an alpha2-adrenergic receptor agonist, produces
ideal sedation and early postoperative recovery for premedication in paediatric
surgery, reducing preoperative anxiety and facilitating smooth induction of
anaesthesia. We performed a meta-analysis to compare the effects of DEX and
midazolam (MDZ) in paediatric anaesthesia with sevoflurane. Methods PubMed, Ovid,
Web of Science, and Public Health Management Corporation were searched through
December 2016 for randomized controlled trials (RCTs) that compared DEX and MDZ
in children undergoing sevoflurane anaesthesia. The risk ratio (RR) with 95%
incidence interval (95%CI) was used for dichotomous variables. Results Twelve
RCTs involving 422 patients in the DEX group and 448 patients in the MDZ group
were included. Patients in the DEX group had a significantly lower incidence of
unsatisfactory sedation (RR [95%CI] = 0.71 [0.57-0.89]), unsatisfactory parental
separation (RR [95%CI] = 0.56 [0.35-0.87]), and rescue analgesia (RR [95%CI] =
0.52 [0.35-0.77]) than patients in the MDZ group. However, both groups had a
similar incidence of unsatisfactory mask acceptance, emergence agitation, and
postoperative nausea and vomiting. Conclusion Compared with MDZ, DEX is
beneficial in paediatric anaesthesia with sevoflurane because of its lower
incidence of unsatisfactory sedation, parental separation, and rescue analgesia.
PMID- 28425832
TI - Use of clear aligners in open bite cases: an unexpected treatment option.
AB - In open bite case treatments, a proper diagnostic differentiation is essential in
determining the appropriate corrective procedures. Dental open bites are
generally more responsive to treatment with orthodontics alone, whereas skeletal
open bites often require a combination of orthodontics and orthognathic surgery.
Patient selection and treatment principles for non-surgical open bite treatment
routinely include fixed appliances both labial or lingual. However, removable
clear aligners have gained a consistent popularity in the treatment of complex
cases including open bite malocclusions. In this article, the authors describe
three different clinical cases in which open bite cases had been satisfactorily
treated by using clear aligners.
PMID- 28425831
TI - Investigating the Phylogenetic Range of Gibberellin Biosynthesis in Bacteria.
AB - Certain plant-associated microbes can produce gibberellin (GA) phytohormones, as
first described for the rice fungal pathogen Gibberella fujikuroi and, more
recently, for bacteria, including several rhizobia and the rice bacterial
pathogen Xanthomonas oryzae pv. oryzicola. The relevant enzymes are encoded by a
biosynthetic operon that exhibits both a greater phylogenetic range and scattered
distribution among plant-associated bacteria. Here, the phylogenetic distribution
of this operon was investigated. To demonstrate conserved functionality, the
enzymes encoded by the disparate operon from X. translucens pv. translucens,
along with those from the most divergent example, found in Erwinia tracheiphila,
were biochemically characterized. In both of these phytopathogens, the operon
leads to production of the bioactive GA4. Based on these results, it seems that
this operon is widely dedicated to GA biosynthesis. However, there is intriguing
variation in the exact product. In particular, although all plant pathogens seem
to produce bioactive GA4, rhizobia generally only produce the penultimate
hormonal precursor GA9. This is suggested to reflect their distinct interactions
with plants, because production of GA4 counteracts the jasmonic-acid-mediated
defense response, reflecting the importance of wounds as the entry point for
these phytopathogens, whereas such suppression presumably is detrimental in the
rhizobial symbiotic relationship.
PMID- 28425833
TI - Management of missing second premolars using miniscrews: an elective solution for
critical anchorage conditions.
AB - Growing patients with congenital missing second premolars should be accurately
evaluated in order to establish an appropriate treatment plan. The decision
whether to close or maintain spaces in dental arches caused by missing teeth
should be based on the consideration of biomechanical factors and the aesthetic
traits of individual patients. Accordingly, the choice of closing spaces requires
an adequate consideration of biomechanical principles in order to avoid
detrimental effects on the occlusion and profile. The effective use of titanium
miniscrews for immediate loading, combined with efficient sliding mechanics,
represents an elective way of successfully treating such cases. The aim of this
article is to describe the procedure and highlight its advantages by giving
details of a clinical case coupled with the results of a long-term follow-up.
PMID- 28425834
TI - Rift Valley fever vaccines: an overview of the safety and efficacy of the live
attenuated MP-12 vaccine candidate.
AB - INTRODUCTION: Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease
endemic to Africa and the Arabian Peninsula. High rates of abortion among
infected ruminants and hemorrhagic fever in infected humans are major public
health concerns. Commercially available veterinary RVF vaccines are important for
preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries;
however, RVFV outbreaks continue to occur frequently in endemic countries in the
21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed
for both animal and human vaccination. This vaccine strain is well attenuated,
and a single dose induces neutralizing antibodies in both ruminants and humans.
Areas covered: This review describes scientific evidences of MP-12 vaccine
efficacy and safety, as well as MP-12 variants recently developed by reverse
genetics, in comparison with other RVF vaccines. Expert commentary: The
containment of active RVF outbreaks and long-term protection from RVF exposure to
infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will
allow immediate vaccination of susceptible animals in case of an unexpected RVF
outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF
control in endemic regions.
PMID- 28425835
TI - Enzymatic synthesis and protein adsorption properties of crystalline nanoribbons
composed of cellulose oligomer derivatives with primary amino groups.
AB - The in vitro enzymatic synthesis of cellulose and its derivatives has attracted
growing interest for fabricating novel cellulose-based supramolecular assemblies
with unique physicochemical and functional properties. However, their potential
biomedical applications have not been sufficiently demonstrated despite their
useful features of designable structures and tailor-made surface functionalities.
Herein, we demonstrated the production of crystalline nanoribbons composed of
cellulose oligomer derivatives with primary amino groups via cellodextrin
phosphorylase-catalyzed single-step reactions using alpha-d-glucose l-phosphate
monomers and 2-aminoethyl-beta-d-glucoside primers. Then, the fundamental
properties of protein adsorption onto the surface-aminated nanoribbons were
systematically investigated. It was found that the primary amino groups on the
nanoribbon surfaces effectively attracted negatively charged proteins but not
positively charged ones. Furthermore, it was demonstrated that the nanoribbons
did not show apparent cytotoxicity against cultured cells. Taken together, our
findings open a new avenue for the facile production of cellulose-based
supramolecular assemblies with tailor-made functionality for future biomedical
applications.
PMID- 28425836
TI - Development and validation of a multi-analyte method for the regulatory control
of carotenoids used as feed additives in fish and poultry feed.
AB - Carotenoids are used in animal nutrition mainly as sensory additives that
favourably affect the colour of fish, birds and food of animal origin. Various
analytical methods exist for their quantification in compound feed, reflecting
the different physico-chemical characteristics of the carotenoid and the
corresponding feed additives. They may be natural products or specific
formulations containing the target carotenoids produced by chemical synthesis. In
this study a multi-analyte method was developed that can be applied to the
determination of all 10 carotenoids currently authorised within the European
Union for compound feedingstuffs. The method functions regardless of whether the
carotenoids have been added to the compound feed via natural products or specific
formulations. It is comprised of three steps: (1) digestion of the feed sample
with an enzyme; (2) pressurised liquid extraction; and (3) quantification of the
analytes by reversed-phase HPLC coupled to a photodiode array detector in the
visible range. The method was single-laboratory validated for poultry and fish
feed covering a mass fraction range of the target analyte from 2.5 to 300 mg kg
1. The following method performance characteristics were obtained: the recovery
rate varied from 82% to 129% and precision expressed as the relative standard
deviation of intermediate precision varied from 1.6% to 15%. Based on the
acceptable performance obtained in the validation study, the multi-analyte method
is considered fit for the intended purpose.
PMID- 28425837
TI - Calprotectin levels in rheumatoid arthritis and their correlation with disease
activity: a meta-analysis.
AB - OBJECTIVE: We evaluated the relationship between calprotectin levels and
rheumatoid arthritis (RA), and the correlation between plasma/serum calprotectin
and RA activity. METHODS: We searched PUBMED, EMBASE, and Cochrane databases and
performed meta-analyses comparing plasma/serum or synovial fluid calprotectin
levels in RA patients and controls, and correlation coefficients between
calprotectin levels and disease activity for 28 joints (DAS28) as well as C
reactive protein (CRP) in RA patients. RESULTS: Sixteen studies including 849 RA
patients and 266 controls were available for meta-analysis. Meta-analysis showed
that calprotectin levels were significantly higher in the RA group than in the
control group (SMD = 2.337, 95% CI = 1.544-3.130, p < 1.0 * 10-8). Stratification
by rheumatoid factor (RF) status revealed significantly elevated calprotectin
levels in the RF-positive RA group compared to that of the RF-negative RA group
(SMD = 0.574, 95% CI = 0.345-0.804, p = 9.2 * 10-7). Meta-analysis of correlation
coefficients identified a significant positive correlation between calprotectin
levels and CRP or DAS28 (correlation coefficient for CRP = 0.566, 95% CI = 0.512
0.615, p < 1.0 * 10-8; correlation coefficient for DAS28 = 0.438, 95% CI = 0.269
0.518, p = 2.5 * 10-6). Calprotectin levels in synovial fluid were significantly
higher in the RA group than in the control group (SMD = 2.891, 95% CI = 1.067
4.715, p = 0.002). CONCLUSIONS: Our meta-analysis demonstrates that circulating
and synovial fluid calprotectin levels are high in patients with RA, and that
circulating calprotectin levels positively correlate with RA activity.
PMID- 28425838
TI - Attending to emotional expressions: no evidence for automatic capture in the dot
probe task.
AB - Research on automatic attention to emotional faces offers mixed results.
Therefore we examined validity effects for facial expressions of different
emotions (compared to neutral faces) with a dot-probe paradigm in seven studies
(total N = 308). Systematic variations of type of emotion, CTI, task, cue size,
and masking allow for a differentiated assessment of attentional capture by
emotions and possible moderating factors. Results indicate a general absence of
emotional validity effects as well as a lack of significant interactions with
either of the manipulated factors, indicating that facial expressions of emotions
do not capture attention in a fully automatic fashion. These findings suggest
that situational and contextual factors have to be taken into account when
investigating attentional capture of emotional faces.
PMID- 28425840
TI - Standardization of Criteria Defining Periodontal Ligament Stem Cells.
PMID- 28425841
TI - Adipocyte hypertrophy-hyperplasia balance contributes to weight loss after
bariatric surgery.
AB - Predictors of weight loss responses are not well-defined. We hypothesized that
adipose tissue phenotypic features related to remodeling would be associated with
bariatric surgery weight loss responses. Visceral and subcutaneous adipose
tissues collected from patients during bariatric surgery were studied with flow
cytometry, immunohistochemistry, and QRTPCR, and results correlated with weight
loss outcomes. Age, male sex, and a diagnosis of type 2 diabetes were associated
with less weight loss. Adipocyte size was increased and preadipocyte frequency
was decreased in visceral adipose tissue from diabetic subjects. Decreased
adipose tissue preadipocyte frequency was associated with less weight loss in
women but not men. These data suggest that phenotypic features of adipose tissue
remodeling may predict responses to weight loss interventions.
PMID- 28425842
TI - Estradiol does not directly regulate adipose lipolysis.
AB - The mechanisms by which estradiol modulates adipose lipolysis are poorly
understood. We sought to measure basal and beta3-stimulated indices of lipoysis
(FFAs, glycerol) in vivo in E2 deficient or supplemented rats, and ex vivo with
direct acute E2 exposure. For 2 weeks, ovariectomized (OVX) and OVX rats treated
with a daily oral dose of E2 (OVX E2) were pairfed to SHAM controls (n = 12 per
group). Adipocyte size was modestly (~40%) increased in OVX rats, but did not
reach significance (p = 0.2). After 2 weeks, half of the animals in each group
received an in vivo injection of saline or 1 mg/kg of the beta3 agonist CL 316,
243. Serum FFA concentrations, but not glycerol, were lower in OVX and OVX E2
rats compared with SHAM controls (p = 0.02). A significant CL response was
present in all groups (p<0.001) and HSL activation was unaffected by OVX or OVX
E2 in retroperitoneal (r.p.) or inguinal (iWAT) adipose depots in vivo. Ex vivo,
CL increased FFA and glycerol accumulation in the media as well as HSL
phosphorylation by several fold in r.p. and iWAT explants, but responses from OVX
and OVX E2 rats were comparable to SHAMs. To assess whether E2 can directly
affect lipolysis, r.p. and iWAT tissue was treated with E2, CL or E2 + CL for 2,
4 or 8 hours using adipose tissue organ culture. CL stimulated FFA release
(p<0.001), but was unaffected by E2. Overall, our results indicate that E2 does
not directly regulate adipose tissue lipolysis.
PMID- 28425843
TI - The dual role of BMP4 in adipogenesis and metabolism.
AB - BMP4 has a well-established role in triggering commitment of mesenchymal stem
cells into the osteogenic and adipogenic linage. We recently described an
additional dual function in adipogenesis: after promoting the formation of both
white and brown pre-adipocytes, Bmp4 drives terminal differentiation into mature
white rather than brown fat cells. Besides this, Bmp4 seems to have a dual role
in metabolism either promoting or repressing oxidative metabolism in a cell
context dependent manner.
PMID- 28425844
TI - The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in
obesity.
AB - Obesity is closely associated with metabolic diseases including type 2 diabetes.
One hallmark characteristics of obesity is chronic inflammation that is
coordinately controlled by complex signaling networks in adipose tissues.
Compelling evidence indicates that reactive oxygen species (ROS) and its related
signaling pathways play crucial roles in the progression of chronic inflammation
in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that
utilizes the glucoses to generate molecular building blocks and reducing
equivalents in the form of NADPH. In particular, NADPH acts as one of the key
modulators in the control of ROS through providing an electron for both ROS
generation and scavenging. Recently, we have reported that glucose-6-phosphate
dehydrogenase (G6PD), a rate-limiting enzyme of the PPP, is implicated in adipose
tissue inflammation and systemic insulin resistance in obesity. Mechanistically,
G6PD potentiates generation of ROS that augments pro-inflammatory responses in
adipose tissue macrophages, leading to systemic insulin resistance. Here, we
provide an overview of cell type- specific roles of G6PD in the regulation of ROS
balance as well as additional details on the significance of G6PD that
contributes to pro-oxidant NADPH generation in obesity-related chronic
inflammation and insulin resistance.
PMID- 28425845
TI - Nck2, an unexpected regulator of adipogenesis.
AB - The regulation of adipose tissue expansion by adipocyte hypertrophy and/or
hyperplasia is the topic of extensive investigations given the potential
differential contribution of the 2 processes to the development of numerous
chronic diseases associated with obesity. We recently discovered that the loss-of
function of the Src homology domain-containing protein Nck2 in mice promotes
adiposity accompanied with adipocyte hypertrophy and impaired function, and
enhanced adipocyte differentiation in vitro. Moreover, in severely-obese human's
adipose tissue, we found that Nck2 expression is markedly downregulated. In this
commentary, our goal is to expand upon additional findings providing further
evidence for a unique Nck2-dependent mechanism regulating adipogenesis. We
propose that Nck2 should be further investigated as a regulator of the reliance
of white adipose tissue on hyperplasia versus hypertrophy during adipose tissue
expansion, and hence, as a potential novel molecular target in obesity.
PMID- 28425846
TI - Alterations to adipose tissue morphology during inflammatory arthritis is
indicative of vasculopathology in DBA/1 mice.
AB - The physiologic function of adipose tissue is altered by the host's inflammatory
response; the implications for maintaining human health and regulating
inflammation-associated disease progression are ill defined. However, this cannot
be investigated in humans, therefore the use of animal models is required. With
the aim to determine morphological and molecular alterations to perivascular and
organ-associated adipose tissues during inflammatory arthritis, collagen-induced
arthritis (CIA) was established in male DBA/1 mice. Emerging evidence from this
study signposts CIA in the DBA/1 mouse as a model that is relevant to study the
development and treatment of early cardiovascular pathology associated with
inflammatory arthritis. Here, we show global morphological changes in adipose
tissue and the thoracic aorta in animals induced with CIA compared with the non
immunized controls. In CIA, we concluded that the increased cell count in PVAT
was, at least in part, caused by an ingress and/or expansion of macrophages that
had a mixed phenotype. A substantial increase of galectin-3 was expressed in PVAT
from mice with CIA. Galectin-3 is elevated in the blood of patients with CVDs,
however, it has never before been measured in PVAT in rodents or humans. Here,
PVAT-associated galectin-3 is identified as a potential biomarker for detecting
early vascular pathology in CIA and a promising candidate for translation to RA.
PMID- 28425847
TI - Form(ul)ation of adipocytes by lipids.
AB - Lipids have the potential to serve as bio-markers, which allow us to analyze and
to identify cells under various experimental settings, and to serve as a clinical
diagnostic tool. For example, diagnosis according to specific lipids that are
associated with diabetes and obesity. The rapid development of mass-spectrometry
techniques enables identification and profiling of multiple types of lipid
species. Together, lipid profiling and data interpretation forge the new field of
lipidomics. Lipidomics can be used to characterize physiologic and
pathophysiological processes in adipocytes, since lipid metabolism is at the core
of adipocyte physiology and energy homeostasis. A significant bulk of lipids are
stored in adipocytes, which can be released and used to produce energy, used to
build membranes, or used as signaling molecules that regulate metabolism. In this
review, we discuss how exhaust of lipidomes can be used to study adipocyte
differentiation, physiology and pathophysiology.
PMID- 28425848
TI - The contribution of bone marrow-derived cells to the human adipocyte pool.
AB - White adipose tissue is a remarkably expandable organ with results in the last
decade showing that human white adipocytes are continuously turned over during
the entire life-span. Data primarily in murine models have demonstrated that
adipocytes are derived from precursors present mainly in the perivascular areas
of adipose tissue but their precise origin remains unclear. Subsets of cells
present in bone marrow display a multipotent differentiation capacity which has
prompted the hypothesis that bone marrow-derived cells (BMDCs) may also
contribute to the adipocyte pool present in peripheral fat depots. This notion
was initially demonstrated in a murine transplantation model, however, subsequent
animal studies have been conflicting resulting in a debate of whether BMDCs
actually differentiate into adipocytes or just fuse with resident fat cells. This
controversy was recently resolved in 2 studies of human subjects undergoing bone
marrow transplantation. Using a combination of different assays these data
suggest that bone marrow contributes to at least 10% of the adipocyte pool. This
proportion is doubled in obesity, suggesting that BMDCs may constitute a reserve
pool for adipogenesis, particularly upon weight gain. This review discusses the
possible mechanisms and relevance of these findings for human pathophysiology.
PMID- 28425849
TI - Age-dependent obesity and mitochondrial dysfunction.
AB - Aging is associated with progressive visceral white adipose tissue (WAT)
expansion both in human and mouse. Importantly, WAT enlargement is initiated
early in life, suggesting that molecular mechanisms underlying age-dependent
obesity are activated at early stages of lifetime. Our recent study found that
age-dependent obesity was associated with a specific decline in mitochondrial
complex IV activity, which leads to reduced fatty acid oxidation and subsequent
adipocyte hypertrophy. At the molecular level, global mitochondrial complex IV
inhibition was driven by hypoxia-inducible factor-1alpha (HIF1alpha)-mediated
repression of some of its key subunits, including cytochrome c oxidase 5b
(Cox5b). In this commentary, we compare age-dependent WAT responses with those
observed in the high fat diet model of extreme obesity. Furthermore, we discuss
the potential scenarios that could initiate age-dependent WAT expansion as well
as the mechanisms by which HIF1alpha could be activated in WAT.
PMID- 28425850
TI - A novel and robust method for testing bimodality and characterizing porcine
adipocytes of adipose tissue of 5 purebred lines of pig.
AB - Adipocyte sizes from adipose tissue of mature animals form a bimodal
distribution, thus reporting mean cell size is misleading. The objectives of this
study were to develop a robust method for testing bimodality of porcine
adipocytes, describe the size distribution with an informative metric, and
statistically test hypertrophy and appearance of new small adipocytes, possibly
resulting from hyperplasia or lipid filling of previously divided fibroblastic
cells. Ninety-three percent of adipose samples measured were bimodal (P <
0.0001); therefore, we describe and propose a method of testing hyperplasia or
lipid filling of previously divided fibroblastic cells based upon the probability
of an adipocyte falling into 2 chosen competing "bins" as adiposity increases. We
also conclude that increased adiposity is correlated positively with an adipocyte
being found in the minor mode (r = 0.46) and correlated negatively with an
adipocyte being found in the major mode (r = -0.22), providing evidence of either
hyperplasia or lipid filling of previously divided fibroblastic cells. We
additionally conclude that as adiposity increases, the mode of the major
distribution of cells occurs at a larger diameter of adipocyte, indicating
hypertrophy.
PMID- 28425852
TI - Discovery of Novel 2-Amino-5-(Substituted)-1,3,4-Thiadiazole Derivatives: New
Utilities for Colon Cancer Treatment.
AB - BACKGROUND: Colon cancer is one of the most widespread disease, the mortality
rate is high due to cancer metastasis and the development of drug resistance. In
this regards, new chemotherapeutic agents with specific mechanisms of action and
significant effect on patient's survival are the new era for the colon cancer
drug development. OBJECTIVE: The main objective of present study was to design,
synthesize of a novel series of 1,3,4-thiadiazole derivatives (VR1 to VR35) and
screen them against HT-29 human colon cancer cell line. METHOD: Newly 1,3,4
thiadiazole scaffold were designed, synthesized and further, characterized by
FTIR, NMR (1H and 13C), MS and elemental analyses. Before the synthesis,
molecular dynamic simulation and ADME studies were performed to find out the most
potent lead compounds. Later, SRB assay using HT-29 cells and ELISA assays were
performed to explore activity and molecular targets of VR24 and VR27 and find out
whether in silico data had a similar pattern in the molecular level. RESULTS: The
results of docking study revealed that both VR24 and VR27 had interaction energy
>-5 kcal/mol with various assigned molecular targets and the ligand-protein
complexes were found to be stable with IL-6. The computational analysis of
molecules showed good ADMET profiling. Later, the in vitro anticancer study was
conducted where VR24 and VR27 were found to be active against HT-29 cells
(GI50<10 uM). Finally, ELISA assays revealed that both the compounds had higher
inhibition properties to various biomarker of colon cancer like IL-6 and COX-2.
CONCLUSION: Collectively, these result suggested that VR24 and VR27 inhibited the
assigned molecular targets, imparting their ameliorative effects against colon
cancer. Due to these encouraging results, we concluded that both VR24 and VR27
may be effective against colon cancer therapy in future.
PMID- 28425851
TI - Altered structure and function of adipose tissue in long-lived mice with growth
hormone-related mutations.
AB - A major focus of biogerontology is elucidating the role(s) of the endocrine
system in aging and the accumulation of age-related diseases. Endocrine control
of mammalian longevity was first reported in Ames dwarf (Prop1df) mice, which are
long-lived due to a recessive Prop1 loss-of-function mutation resulting in
deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin.
Following this report, several other GH-related mutants with altered longevity
have been described including long-lived Snell dwarf and growth hormone receptor
knockout mice, and short-lived GH overexpressing transgenic mice. One of the
emerging areas of interest in these mutant mice is the role of adipose tissue in
their altered healthspan and lifespan. Here, we provide an overview of the
alterations in body composition of GH-related mutants, as well as the altered
thermogenic potential of their brown adipose tissue and the altered cellular
senescence and adipokine production of their white adipose tissue.
PMID- 28425853
TI - Evaluation of the in vitro Chemosensitivity and Correlation with Clinical
Outcomes in Lung Cancer using the ATP-TCA.
AB - BACKGROUND AND OBJECTIVE: Multiple drug resistance (MDR) to chemotherapeutic
agents often leads to a failure to respond to chemotherapy. We utilized an in
vitro chemosensitivity test to identify sensitive and effective chemotherapeutic
drugs and further elucidated the correlation between the in vivo chemosensitivity
and clinical outcomes. METHODS: Here, we evaluated the in vitro chemosensitivity
and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291
lung cancer patients to seven chemotherapy regimens using an ATP-based tumor
chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of
lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma
patients (90 cases) to these single-drug and chemotherapy regimens were compared.
Furthermore, the correlations between the chemosensitivity and clinical outcomes
were investigated in 16 stage III squamous cell carcinoma patients. RESULTS AND
CONCLUSION: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP
(54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates.
Approximately 31.7% of patients developed resistance to all eight single-drug
chemotherapies, and 25.8% of patients displayed resistance to all seven
chemotherapy regimens. In addition, lung squamous cell carcinoma was
significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma
(P<0.05). Further analysis showed that patients with higher drug sensitivity
tended to have longer disease-free survival (18 months vs. 8.5 months) than
patients displaying drug resistance (P<0.05). These results suggest that the
implementation of in vitro drug susceptibility testing before chemotherapy can
effectively prevent the occurrence of primary drug resistance and inappropriate
drug treatment.
PMID- 28425854
TI - Rationale Design, Synthesis, Cytotoxicity Evaluation, and Molecular Docking
Studies of 1,3,4-oxadiazole Analogues.
AB - BACKGROUND: 1,3,4-Oxadiazole heterocycles possess a broad spectrum of biological
activities. They were reported as potent cytotoxic agents and tubulin inhibitors;
hence it is of great interest to explore new oxadiazoles as cytotoxic agents
targeting tubulin polymerization. OBJECTIVE: Two new series of oxadiazoles (5a-h
and 12a-h) were synthesized, structurally related to the heterocyclic linked aryl
core of IMC-038525, NSC 776715, and NSC 776716, with further modification by
incorporating methylene linker. METHOD: The 2,5-disubstituted-1,3,4-oxadiazoles
(5a-h and 12a-h) were synthesized by refluxing an equimolar mixture of the
intermediates [(4) and (8a-d)] and aromatic aldehydes in water-ethanol system
using sodium bisulphite catalyst. The cytotoxicity evaluation was carried out
according to the National Cancer Institute (NCI US) Protocol, while the tubulin
polymerization assay kits from Cytoskeleton TM(bk011p) was used to perform an in
vitro tubulin polymerization assay. RESULTS: 2-(5-{[(4-Chlorophenyl)amino]methyl}
1,3,4-oxadiazol-2-yl)phenol (5f) and 2-[(2,4-dichlorophenoxy) methyl]-5-(3,4
dimethoxyphenyl)-1,3,4-oxadiazole (12c) showed maximum cytotoxicity with the mean
percent growth inhibitions (GIs) of 71.56 and 72.68 respectively at 10 uM drug
concentrations. Both the compounds (5f and 12c) showed superior cytotoxicity than
clinically prevalent anticancer drugs, Imatinib and Gefitinib in one dose assay.
The compound 12c showed promising results in five dose assay, with GI50 values
varies between 1.61 and >100 uM. Furthermore, the compounds, 5f and 12c also
inhibited the polymerization of tubulin with, an IC50 of 2.8 and 2.2 uM,
respectively. CONCLUSION: The oxadiazoles reported herein are tubulin inhibitors
and cytotoxic agents. These findings will be helpful in future drug design of
more potent tubulin inhibitor cytotoxic agents.
PMID- 28425855
TI - Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy.
AB - The aberrant proliferation of tumor cells and abundant vasculature in tumor
tissues are closely correlated with receptors that are specifically dysregulated
in tumor cells. These tumor-associated targets are critical in early diagnosis
and therapy selection. Ligands such as antibodies, proteins, polypeptides and
polysaccharides that specifically bind to these targets can significantly improve
the detection and cure rate when used as tumor imaging probes or anti-tumor
agents. Compared to other targeting ligands, peptides have attracted increasingly
more attention in tumor diagnostics and therapeutics because of their small
sizes, high affinity, stability, ease of modification and low immunogenicity.
Several peptide-based imaging probes and therapeutic agents have already been
used in clinical trials. This review summarizes some of the tumor-associated
targets and their corresponding peptides, as well as the potential of these
peptides in cancer treatment.
PMID- 28425856
TI - Apicidin Inhibited Proliferation and Invasion and Induced Apoptosis via
Mitochondrial Pathway in Non-small Cell Lung Cancer GLC-82 Cells.
AB - BACKGROUND: Apicidin, as an inhibitor of histone deacetylase, showed a wide range
of antiproliferative activity against various cancer cell lines. Apicidin has
also been reported to induce apotosis via Fas/Fas ligand. Yet few studies have
been focused on mitochondrial pathway for its anti-tumor activity. OBJECTIVE: In
this study, we evaluated its involved mitochondrial mechanism against non-small
cell lung cancer GLC-82 cells. METHOD: Apicidin was isolated from the mangrove
endophtic fungi Fusarium sp. by solvent extraction and column chromatography. Its
structure was elucidated by MS and NMR spectroscopic data, and comparison of
those data with published data. Furthermore, anti-tumor activity and
mitochondrial pathway of apicidin against GLC-82 cells were studied. RESULTS:
Apicidin was obtained from secondary metabolites of Fusarium sp., and it showed
potent inhibitory activity against GLC-82 cells with the IC50 value of 6.94 +/-
0.27 uM. Furthermore, apicidin suppressed proliferation and invasion, and induced
apoptosis via mitochondrial pathway in GLC-82 cells, including loss of DeltaPsim,
release of cytochrome c from mitochondria, activation of caspase-9 and -3, and
cleavage of poly-ADP-ribose polymerase. CONCLUSION: Apicidin, an inhibitor of
histone deacetylase obtained from the mangrove endophytic fungi Fusarium sp., not
only inhibited proliferation and invasion of GLC-82 cells, but also induced
apoptosis via the mitochondrial pathway.
PMID- 28425857
TI - Antioxidant Properties of Fractions for Unripe Fruits of Capsicum annuum L. var.
Conoides.
AB - BACKGROUND: Capsicum plant, especially for C. annuum, is an abundant resource for
bioactive antioxidants, but few studies have examined the unripe fruit part of
the Capsicum plant. OBJECTIVE: MeOH extract of unripe fruits of C. annuum L. var.
conoides (UFCA) was chromatographed over a silica gel column using a gradient of
CH2Cl2/MeOH as eluent to produce 9 fractions. Antioxidant activities are
evaluated along with cell viabilities of 9 fractions of UFCA. METHOD: The
antioxidant properties were analyzed in terms of total phenol content (TPC),
total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical
scavenging, 2,2-azinobis (3-ethyl-benzothiazoline-6- sulfonic acid) (ABTS)
radical scavenging, ferric reducing, and ferrous ion-chelating ability. The cell
viability of human oral cancer cells (Ca9-22) was measured by 3-(4,5
dimethylthiazol-2-yl)-(3-carboxymethoxyphenyl)-2- (4-sulphophenyl)-2H-tetrazolium
(MTS) assay. RESULTS: Except for TFC, fractions (Frs.) 1 and 2 showed the lowest
level of these antioxidant properties. Frs. 3 to 9 showed dose-responsive
induction for antioxidant effects. Fr. 8 and Fr. 5 respectively showed the
highest levels of TPC and TFC for 1162 +/- 11 gallic acid equivalents (GAE)
(mg)/UFCA (g) and 1295 +/- 32 quercetin equivalents (QCE) (mg)/UFCA (g). The cell
viability of Fr. 3 was moderately decreased (78.2%) while those of Frs. 4, 5, and
9 were dramatically decreased (55.6, 57.8, and 46.8%, respectively) in oral
cancer Ca9-22 cells. UFCA-derived 14 compounds/mixtures derived from Frs. 1, 2,
3, 4, and 8 displayed differential antioxidant performance for these analyses.
CONCLUSION: Taken together, fractions of UFCA displayed diverse antioxidant and
anticancer effects for oral cancer cells. Some fractions of UFCA may be potent
natural antioxidant supplements for antioral cancer cell treatment.
PMID- 28425858
TI - Nano-encapsulation of Dietary Phytoconstituent Capsaicin on Emulsome: Evaluation
of Anticancer Activity Through the Measurement of Liver Oxidative Stress in Rats.
AB - BACKGROUND: Excessive reactive species derived from oxygen and nitrogen leads to
oxidative damage to tissue and organs. Capsaicin (CAP), a pungent component found
in red pepper can prevent oxidative stress. OBJECTIVE: The aim of the present
work was to evaluate the protective effects of CAP loaded nano-emulsomes (EML)
against the oxidative stress of rat livers induced through sodium fluoride (NaF).
METHOD: EML was prepared by thin film hydration method that is development of
thin lipid film followed by hydration and sonication. EML was characterized by
Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD)
techniques. EML was evaluated for drug entrapment, in vitro drug release, and in
vivo study. RESULTS: In vitro drug release study of optimized formulation showed
that 50% of CAP was released within 50.21 min while 85% CAP was released in 227.4
min. Single oral dose of free CAP and CAP loaded EML were given to rats 2 hour
after NaF administration. Membrane of hepatic cells was damaged by NaF and it was
judged by the estimation of lipid peroxidation, reactive oxygen species (ROS),
and catalase activity. The administration of CAP loaded EML 2 hr after NAF
consumption showed significant decrease in ROS level compared to free CAP. EML
containing CAP was more effective in comparison to free CAP in controlling the
lipid peroxidation that is thiobarbituric acid substance augmentation in liver by
the treatment of NaF. The administration of CAP loaded EML showed significant
increase in catalase activity compared to free CAP administration. CONCLUSION:
The results clearly demonstrated that CAP loaded EML may be accepted as an
effective therapeutic formulation in preventing oxidative damage.
PMID- 28425859
TI - Synthesis, Characterization, and Inducing Tumor Cell Apoptosis of Two Ru(II)
Complexes Containing Guanidinium as Ligands.
AB - DESCRIPTION: Two new ruthenium(II) complexes containing guanidinium as ligands,
[Ru(dip)2 (L1)]3+ (Ru1) and [Ru(dip)2(L2)]3+ (Ru2) (dip=4,7-diphenyl-1,10
phenanthroline; L1=1-(4-(1H-imidazo[4,5- f][1,10]phenanthrolin-2
yl)phenyl)guanidine cation; L2 = 1-(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)
phenyl)guanidine cation) have been synthesized and characterized. Both complexes
display higher cytotoxicity against several cancer cell lines compared to
cisplatin and are less cytotoxic on the nontumorigenic cell line LO2.
Intracellular distribution studies show that these complexes are selectively
localized in the cytoplasm. FINDINGS: Further analysis revealed that Ru1 and Ru2
had no obvious effects on the cell cycle and induced apoptosis in HeLa cells via
the mitochondrial pathway, which involved reactive oxygen species (ROS)
accumulation, mitochondrial dysfunction, and Bcl-2 family member activation.
Taken together, the two complexes have the potential to be utilized as anticancer
agents.
PMID- 28425860
TI - A Novel Recombinant Multi-Epitope Vaccine Could Induce Specific Cytotoxic T
Lymphocyte Response In Vitro and In Vivo.
AB - BACKGROUND: Malignant tumor is still one of the important diseases worldwide,
cytotoxic CD8+ T lymphocytes (CTLs) play an important role in killing tumor
cells. OBJECTIVE: To enhance the immune response of our previously identified HLA
A2-restricted CTL epitopes, we designed a multiepitope YL66. METHOD: The fusion
protein GST-YL66 and DNA vaccine pcDNA3.1(+)-YL66 were used to induce CTLs from
human peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donors and
and in HLA-A2.1/Kb transgenic(Tg) mice. and the activity of induced CTLs were
tested by IFN-gamma relesde ELISPOT assay and LDH cytotoxicity assay. RESULTS:
GST-YL66 induced CTL could lysis tumor cells and release IFN-gamma both in vitro
and in vivo, and pcDNA3.1(+)-YL66 could also induce significant CTL response in
vivo. CONCLUSION: The designed fusion multiepitope YL66 could be used as a
vaccine against patients with tumors expressing COX-2 and/or MAGE-4.
PMID- 28425861
TI - Role of Cysteine Residues in Regulation of Peptidyl-prolyl cis-trans Isomerase
Activity of Wheat Cyclophilin TaCYPA-1.
AB - BACKGROUND: The wheat cyclophilin, TaCYPA-1, shows peptidyl-prolyl cis-trans
isomerase (PPIase) activity. However, the significance of different cysteine
residues in regulation of PPIase activity of this protein has not been
investigated. OBJECTIVES: The main objective of this study was to analyze the
role of different disulphide linkages in redox mechanisms that modulate the
PPIase activity of TaCYPA-1. METHOD: Site-directed mutants of TaCYPA-1 were
generated by substituting cysteine residues at positions -40 and -122 with serine
and -126 with proline. The recombinant proteins were expressed in Escherichia
coli and purified. The effect of Cu2+ and N-ethylmaleimide was studied on PPIase
activity of the purified recombinant cyclophilins for analyzing the role of
different cysteine residues in the modulation of enzyme activity. The changes in
secondary structure of TaCYPA-1 and its mutants were analysed by recording far UV
CD spectra. The effect of different cysteine substitutions on thermotolerance of
E. coli was studied by monitoring the cell growth at 47 degrees C after 2 h, 3 h
and 5 h of heat stress. RESULTS: The catalytic efficiencies (Kcat/Km) of TaCYPA
1C40S (0.37 X 106 M-1 s-1) and TaCYPA- 1C122S (0.31 X 106 M-1 s-1) were
significantly lower as compared to the native TaCYPA-1 (1.33 X 106 M-1 s-1),
whereas Kcat/Km of the double mutant TaCYPA-1C40S/C122S was significantly higher
(2.36 X 106 M-1 s-1). Compared to the wild-type TaCYPA-1, the different mutants
also showed differential sensitivity to Cu2+. Furthermore, the results of this
study also revealed that despite lacking PPIase activity, the mutant TaCYPA
1C126P was able to confer partial protection against heat stress. CONCLUSION:
This study revealed that mutation of different cysteine residues in TaCYPA-1
results in differential effect on PPIase activity. It was also observed that of
the two pairs of cysteine residues i.e. Cys40/Cys168 and Cys122/Cys126, the
latter appears to play major role in redox regulation of TaCYPA-1. The mutant
TaCYPA-1C126P, though lacking PPIase activity, was able to impart partial
tolerance to heat stress in E. coli, suggesting other functions besides cis to
trans isomerisation. This study, therefore, provides new insights into the
regulation of plant cyclophilins.
PMID- 28425862
TI - The Impact of IL-17 in Atherosclerosis.
AB - Atherosclerosis is a chronic vascular disease in which atherosclerotic plaques
develop in the arterial wall. It is believed that inflammation plays a major role
in atherosclerotic formation and progression. Thus, atherosclerosis can be
considered as an inflammatory disease of the arterial vessel. Mouse model
demonstrated that T and B cell deficiency reduces the atherosclerotic burden in
the formation of an atherosclerotic lesion. CD4+ T helper cells (Th), such as Th1
cells known being the major CD4+ T cell subtype found in mouse models of
atherogenesis, increase plaque formation caused by oxLDL. IL-17 (also known as IL
17A) was produced by T cells or by a unique subset of T helper cells. IL-17
producing T cells express interferon- gamma (IFN-gamma), an important regulator
of immune function, which is highly expressed in atherosclerotic lesions, defying
their neat characteristics as Th17 cells. Regulation of Th17 signal pathway may
play a significant role in the pathogenesis of multiple inflammatory and
autoimmune disorders, such as atherosclerosis. In this review, the structural
features of IL-17 family and their roles involved in atherosclerosis are
described.
PMID- 28425863
TI - Targeted Drug Delivery Based on Gold Nanoparticle Derivatives.
AB - Drug delivery systems are effective and attractive methods which allow
therapeutic substances to be introduced into the body more effectively and safe
by having tunable delivery rate and release target site. Gold nanoparticles
(AuNPs) have a myriad of favorable physical, chemical, optical, thermal and
biological properties that make them highly suitable candidates as non-toxic
carriers for drug and gene delivery. The surface modifications of AuNPs
profoundly improve their circulation, minimize aggregation rates, enhance
attachment to therapeutic molecules and target agents due to their nano range
size which further increases their ability to cross cell membranes and reduce
overall cytotoxicity. This comprehensive article reviews the applications of the
AuNPs in drug delivery systems along with their corresponding surface
modifications. The highlighting results obtained from the preclinical trial are
promising and next five years have huge possibility move to the clinical setting.
PMID- 28425864
TI - Editorial: Phytochemicals and their Effects on Human Health.
PMID- 28425865
TI - Editorial: HIV and Antiretroviral Drugs: Current Status and New Challenges.
PMID- 28425866
TI - Recent Development of Oridonin Derivatives with Diverse Pharmacological
Activities.
AB - Oridonin is one of the major components isolated from Isodon rubescens, a
traditional Chinese medicine, and it has been confirmed to exhibit many kinds of
biological activities including anticancer, anti-inflammation, antibacterial and
so on. However, the poor pharmaceutical property limits the clinical applications
of oridonin. So many strategies have been explored in the purpose of improving
the potencies of oridonin, and structure modification is one thus way. This
review outlines the landscape of recent development of oridonin derivatives with
diverse pharmacological activities, mainly focusing on the biological properties,
structure-activity relationships, and mechanism of actions.
PMID- 28425867
TI - Chemokines and Relevant microRNAs in the Atherogenic Process.
AB - Chemokines play a significant role in initial and advanced steps of
atherogenesis. In early steps, chemokines control the adhesion of leukocytes to
endothelial cells (ECs) followed by transmigration of monocytes and their
deposition in the intima where they differentiate to proinflammatory macrophages.
Except for proinflammatory activity, chemokines are responsible for homeostasis
and homing of progenitor cells. Recently, microRNAs (miRs) were found to control
expression and activity of chemokines in ECs, vascular smooth muscle cells
(VSMCs), and macrophages at different steps of atherogenesis. Expression of the
proatherogenic chemokine CXCL1 is suppressed by miR-181 that down-regulates
nuclear transcription factor NF-kB stimulation in ECs therefore weakening the
adhesiveness of the endothelium for monocytes. MiR-126 activates the endothelial
production of a chemokine CXCL12 via self-multiplying feedback loop to promote re
endothelialization and support lesion stability. MiR-155 is proatherogenic by
induction of the inflammatory chemokine CCL2 in macrophages. In fact, chemokines,
their receptors, and relevant miRs form a complex network that exerts pro- and
anti-inflammatory properties in vascular cells during different steps of
atherogenic process. Obtaining new information about complicated relations
between miRs and chemokines may create prerequisites for the development of novel
approaches to treat atherosclerosis.
PMID- 28425868
TI - Pomegranate as a Possible Treatment in Reducing Risk of Developing Wound Healing,
Obesity, Neurodegenerative Disorders, and Diabetes Mellitus.
AB - Four distinguished although overlying stages make up the methodical procedure of
wound healing, which are hemostasis, inflammation, proliferation and remodelling.
Multiple sclerosis (MS) is described as an incessant inflammatory central nervous
system disease, and is linked with neurodegeneration, demyelination, as well as
susceptibility to oxidative pressure. Obesity signifies a swiftly developing
danger to the wellbeing of populations in a rising number of nations. Usually
called diabetes mellitus (DM) by medical practitioners, diabetes details a
collection of metabolic diseases within which the individual has raised blood
glucose, either due to an insufficiency of insulin generation, or the lack of
suitable response by the body to insulin, or both. Conventionally, the
pomegranate, as well as its flowers, leaves, fruit juice and tree bark, has been
applied in the treatment of conditions including acidosis, haemorrhage, diarrhoea
and microbial contagions. Extracts of pomegranate have been established to
contain intense anti-inflammatory, antioxidant as well as antitumor features in
vivo as well as ex vivo. Of late, beneficial consequences of decrease of fat have
been illustrated employing the pomegranate as well as its extracts. Several of
the favourable consequences are associated with the availability of anthocyanins,
tannins, and considerably elevated amounts of antioxidants, as well as flavonoids
and polyphenols. A summary of the endeavours applied to deal with the possible
advantages of the pomegranate towards healing wounds, Alzheimer's disease (AD),
diabetes mellitus (DM) and obesity, as well as an appraisal of the efficiency of
intervention through the pomegranate and its extracts is provided in this
article.
PMID- 28425869
TI - Development of a Chitosan-based Nanoparticle Formulation for Ophthalmic Delivery
of Honokiol.
AB - BACKGROUND: Retinal neovascularization (NV) is the leading cause of blindness in
the majority of ocular diseases. Several treatment approaches have been developed
for retinal NV; of these methods, instillation of nanoparticles into the
conjunctival sac has shown potential for retinal NV treatment because it does not
cause physical damage and is easy to operate. METHODS: In this study, honokiol
loaded chitosan/sulfobutylether-beta-cyclodextrin nanoparticles (HKCS- NPs) were
prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol
and sulfobutylether-beta-cyclodextrin was used to incorporated insoluble honokiol
into chitosan nanoparticles, which were prepared through ionotropic gelation.
RESULTS: HK-CS-NPs featured a spherical surface with a narrow size distribution
of polydispersity index less than 0.250, a mean size range of 373-523 nm, a
positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of
84.92%. In vitro release studies showed an initial burst release phase and a
sustained release phase of nanoparticles. Moreover, in vivo study showed that HK
CS-NPs exhibited good ocular tolerability and could improve ophthalmic
bioavailability of honokiol. In particular, the maximum concentration of honokiol
after administration of HK-CS-NPs was enhanced by 1.65 times compared with that
after instillation of the honokiol suspension alone. CONCLUSION: This study
proposes HK-CS-NPs as a potential ophthalmic delivery system.
PMID- 28425870
TI - iPreny-PseAAC: Identify C-terminal Cysteine Prenylation Sites in Proteins by
Incorporating Two Tiers of Sequence Couplings into PseAAC.
AB - BACKGROUND: Occurring at the cysteine residue in the C-terminal of a protein,
prenylation is a special kind of post-translational modification (PTM), which may
play a key role for statin in altering immune function. Therefore, knowledge of
the prenylation sites in proteins is important for drug development as well as
for in-depth understanding the biological process concerned. OBJECTIVE: Given a
query protein whose C-terminal contains some cysteine residues, which one can be
of prenylation or none of them can be prenylated? METHODS: To address this
problem, we have developed a new predictor, called "iPreny-PseAAC", by
incorporating two tiers of sequence pair coupling effects into the general form
of PseAAC (pseudo amino acid composition). RESULTS: It has been observed by four
different cross-validation approaches that all the important indexes in
reflecting its prediction quality are quite high and fully consistent to each
other. CONCLUSION: It is anticipated that the iPreny-PseAAC predictor holds very
high potential to become a useful high throughput tool in identifying protein C
terminal cysteine prenylation sites and the other relevant areas. To maximize the
convenience for most experimental biologists, the webserver for the new predictor
has been established at http://app.aporc.org/iPreny-PseAAC/, by which users can
easily get their desired results without needing to go through the mathematical
details involved in this paper.
PMID- 28425871
TI - The Journey of the Non-Vascular Relief for Migraine: From 'Triptans' To 'Ditans'.
AB - Migraine is a recurrent, disabling, complex and highly prevalent neurological
disorder. The mystery behind the cause of migraine is continuously evolving,
according to the scientific understanding of the disease. This growing
understanding helps to identify novel therapeutic targets for the management of
migraine to treat the ailing migraineurs. The role of serotonin (5HT) in migraine
is recognized to be the cornerstone for the currently available therapeutic
options namely ergot alkaloids and triptans. The role of mediators such as
Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory
neurotransmitter glutamate, has been realized and ignited the development of
drugs targeting these factors. Lasmiditan, known as a Neurally Active Anti-
Migraine Agent (NAAMA) is a specific 5HT1F agonist, developed as a new group
named as 'ditans'. The drug was designed and developed to meet the unmet needs of
currently available medications to circumvent the vascular adverse effects.
Having a group of drugs with a nonvascular mechanism of action, devoid of
unwanted effects with a different spectrum of indication and contraindications,
is the need of the hour to expand the armamentarium available to tackle acute
migraine attack.
PMID- 28425872
TI - Increase in human immunodeficiency virus 1 diversity and detection of various
subtypes and recombinants in north-eastern Brazil.
AB - PURPOSE: Diverse human immunodeficiency virus 1 (HIV-1) subtypes and circulating
recombinant forms are found in Brazil. The majority of HIV-1 molecular
epidemiological studies in Brazil have been conducted in the southern and south
eastern regions of the country, although several recent studies in the north
eastern region have addressed this issue. The objective of this study was to
molecularly characterize HIV-1 circulating in Pernambuco, north-eastern Brazil.
METHODOLOGY: A total of 64 samples were collected from 2002 to 2003, and another
103 were collected from 2007 to 2009. The protease and partial reverse
transcriptase regions of the HIV-1 polymerase-encoding (pol) gene were sequenced,
and subtyping, recombination and phylogenetic analyses were performed.Results/Key
findings. Subtype B (60.9 %) was found to be predominant, followed by HIV-1 F
(31.4 %). Several BF recombinants (4.2 %), and BC and AG recombinants were also
identified. The intra-subtype genetic diversity was estimated to be 0.065 (sd+/
0.004) for HIV-1 B and 0.055 (sd+/-0.004) for HIV-1 F, reflecting a greater
accumulation of mutations in subtype B (P<0.01). More codons were found to be
under positive selective pressure in samples collected from 2007 to 2009, from
individuals with a T-cell count>=200 cells mm-3 and from women. Coalescence data
indicated that the subtype F population has been continuously expanding.
CONCLUSIONS: HIV-1 shows high genetic diversity in the state of Pernambuco. Thus,
additional molecular evaluations of circulating strains will provide a better
understanding of the epidemic and may lead to more effective preventive
strategies.
PMID- 28425873
TI - Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in
extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using
Xpert MTB/RIF.
AB - BACKGROUND: Tuberculosis (TB) is a serious public health problem in developing
countries such as Pakistan. Rapid diagnosis of TB and detection of drug
resistance are very important for timely and appropriate management of multidrug
resistant TB (MDR-TB). OBJECTIVE: The purpose of this study was to determine the
diagnostic efficacy of the Xpert MTB/RIF assay for rapid diagnosis of TB and
detection of rifampicin (RIF) resistance in extrapulmonary and smear-negative
pulmonary TB suspects. METHODS: A total of 98 bronchoalveolar lavage fluid (BALF)
and 168 extrapulmonary specimens were processed by Xpert MTB/RIF. Culture results
are considered as the gold standard for diagnosis of TB, and drug susceptibility
testing for detection of RIF resistance. Diagnostic efficacy was measured in
terms of sensitivity, specificity and positive and negative predictive values.
RESULTS: The Xpert MTB/RIF assay detected 40 (40.8 %) of 98 BALF of presumptive
pulmonary TB and 60 (35.7 %) of 168 extrapulmonary specimens. Sensitivity and
specificity of the Xpert MTB/RIF assay for detection of TB was 86 and 88.4 %,
respectively. The positive predictive value was 71.5 % while negative predictive
value was 95.1 %. CONCLUSION: The Xpert MTB/RIF assay is a rapid and simple
technique with high sensitivity and specificity for diagnosing TB and detecting
drug resistance in extrapulmonary and smear-negative TB cases.
PMID- 28425874
TI - In vitro and in vivo assessments of Rhodomyrtus tomentosa leaf extract as an
alternative anti-streptococcal agent in Nile tilapia (Oreochromis niloticus L.).
AB - PURPOSE: Rhodomyrtustomentosa is a Thai medicinal plant that has been attracting
attention for its remarkable antibacterial properties against Gram-positive
pathogenic bacteria. The purpose of this study was to evaluate the antibacterial
properties of R. tomentosa leaf extract against Streptococcus agalactiae and
Streptococcus iniae isolated from infected tilapia. METHODOLOGY: The anti
streptococcal activity of R. tomentosa was determined using broth microdilution
assays. RESULTS: The extract demonstrated strong antibacterial activity against
the fish pathogens, with minimum inhibitory concentrations (MICs) ranging from
7.8-62.5 ug ml-1. It was found to possess a dose-dependent bacteriostatic effect
on this organism. Scanning electron microscopy revealed irregular and long chains
of swollen cells, as well as corkscrew shapes andincomplete separation of cell
division of S. agalactiae cells following the treatment at sub-MIC. Moreover, S.
agalactiae cells pre-treated with the extract became more sensitive to oxidative
stress induced by H2O2 than the untreated cells. Based on the mortality of Nile
tilapia after intraperitoneal infection of S. agalactiae at median lethal dose
(LD50), the pre-treated cells caused a significant (P<0.01) reduction in
mortality of S. agalactiae-infected Nile tilapia. CONCLUSION: The results
suggested that R. tomentosa could be further developed as a simple and effective
agent for the treatment of streptococcosis in Nile tilapia.
PMID- 28425875
TI - Occurrence of qnrB1 and qnrB12 genes, mutation in gyrA and ramR, and expression
of efflux pumps in isolates of Klebsiella pneumoniae carriers of blaKPC-2.
AB - PURPOSE: The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the
presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux
pumps (acrB and acrF) and mutations in the gene ramR. METHODOLOGY: Were
investigated in 30 blaKPC-2-positive isolates of Klebsiella pneumoniae taken from
infection and colonization in hospital patients from Recife-PE, Brazil. The
detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR
and the quinolone-resistance-determining regions of gyrA, gyrB and parC were
performed by PCR followed by DNA sequencing. RESULTS: Among the isolates
analysed, 73.3 % (n=22) presented the qnrB gene. For the DNA sequencing, six
isolates (K3-A2, K12-A2, K25-A2, K27-A2, K19-A2 and K3-C2) were selected and the
qnrB1 and qnrB12 variants were detected. This is the first ever report, to the
best of our knowledge, of the presence of qnrB12 in K. pneumoniae. This is also
the first report, to the best of our knowledge, of the presence of qnrB1 or
qnrB12 with blaKPC-2 in K. pneumoniae in Brazil. Mutations were observed in gyrA
S83 and in ramR. All isolates presented genes for the acrB and acrF efflux pumps
and the reverse transcription PCR performed showed that the pumps were being
expressed. CONCLUSION: KPC-2-positive isolates colonizing patients, which also
showed qnrB, mutation in gyrA and efflux pumps, may be important reservoirs for
disseminating these resistance mechanisms in the hospital environment.
PMID- 28425876
TI - Characterization of the translation elongation factor 1-alpha gene in a wide
range of pathogenic Aspergillus species.
AB - PURPOSE: We aimed to evaluate the resolving power of the translation elongation
factor (TEF)-1alpha gene for phylogenetic analysis of Aspergillus species.
METHODOLOGY: Sequences of 526 bp representing the coding region of the TEF-1alpha
gene were used for the assessment of levels of intra- and inter-specific
nucleotide polymorphism in 33 species of Aspergillus, including 57 reference,
clinical and environmental strains. RESULTS: Analysis of TEF-1alpha sequences
indicated a mean similarity of 92.6 % between the species, with inter-species
diversity ranging from 0 to 70 nucleotides. The species with the closest
resemblance were A. candidus/A. carneus, and A. flavus/A. oryzae/A. ochraceus,
with 100 and 99.8 % identification, respectively. These species are
phylogenetically very close and the TEF-1alpha gene appears not to have
sufficient discriminatory power to differentiate them. Meanwhile, intra-species
differences were found within strains of A. clavatus, A. clavatonanicus, A.
candidus, A. fumigatus, A. terreus, A. alliaceus, A. flavus, Eurotium amstelodami
and E. chevalieri. The tree topology with strongly supported clades (>=70 %
bootstrap values) was almost compatible with the phylogeny inferred from analysis
of the DNA sequences of the beta tubulin gene (BT2). However, the backbone of the
tree exhibited low bootstrap values, and inter-species correlations were not
obvious in some clades; for example, tree topologies based on BT2 and TEF-1alpha
genes were incompatible for some species, such as A. deflectus, A. janus and A.
penicillioides. CONCLUSION: The gene was not phylogenetically more informative
than other known molecular markers. It will be necessary to test other genes or
larger genomic regions to better understand the taxonomy of this important group
of fungi.
PMID- 28425877
TI - Me, the Editor-In-Chief and the Puzzle Work.
PMID- 28425878
TI - Medical Education in Portugal.
PMID- 28425879
TI - Continuing Medical Education in Portugal: A New Era?
PMID- 28425880
TI - [Narrative Medicine: An Optative Course at the Faculty of Medicine of Lisbon].
PMID- 28425881
TI - [On the Future of Portuguese Physician-Scientists].
PMID- 28425882
TI - Associations Between the Big Five Personality Traits and a Medical School
Admission Interview.
AB - INTRODUCTION: Personality has became popular in medical student's selection.
However, few research exists about the association between the big five
personality traits and the existent medical school selection tools. Our aim was
to study which personality traits were selected by a medical school admission
interview. MATERIAL AND METHODS: One hundred ninety four graduate applicants that
had applied to the Faculty of Medicine of the University of Porto through the
graduate entry approach, after ranked on previous achievement, were interviewed
between the academic years of 2011 and 2013. From these, 181 (93.3%) answered to
the NEO Five-Factor Inventory that assesses high order personality traits of
openness to experience, conscientiousness, extraversion, agreeableness and
neuroticism. Admission interview corresponded to the second phase of the
seriation process. Every applicant was interviewed and scored by three
interviewers on seven dimensions asesssed by Lickert scale (1-10). Interview
score was the sum of the dimensions. Linear mixed effects model and respective
regression coefficients were used to estimate the association between personality
traits from each interviewer's score. Final models were adjusted for gender,
interviewers and previous achievement. RESULTS: Openness to experience (Beta =
0.18: CI 95%: 0.05; 0.30) had the strongest association with interview score
followed by the interaction effect between the extraversion and conscientiousness
traits (Beta = 0.14; CI 95%: 0.02; 0.25). Also, applicants scored higher when
their gender was opposite to the interviewers. DISCUSSION: Previous achievement
and interview score had no association. CONCLUSION: Our admission interview
selected different personality traits when compared to other selection tools.
Medical schools should be aware of the implications of the adopted selection
tools on the admitted medical student's personality because it can help providing
beneficial interventions.
PMID- 28425883
TI - Transition from Secondary School to Medical School: The Role of Self-Study and
Self-Regulated Learning Skills in Freshman Burnout.
AB - INTRODUCTION: The transition from secondary to higher education is a challenging
and demanding period for medical students. The ability to manage study time
effectively and to be a self-regulated learner is essential to cope with the
exponential growth of knowledge in medical education. Thus, the purpose of our
study was to measure self-regulated learning skills and self-study across
secondary higher education transition and to explore its effect on academic
burnout in the first year of medical school. MATERIAL AND METHODS: We collected
data from 102 (43%) freshman medical students on self-regulated learning,
academic achievement, and hours of self-study/week relative to last year of
secondary school (at the beginning of academic year) and the first year of
medical school (at the end of academic year). Burnout data was collected at the
end of academic year. RESULTS: Among the 102 participants, 12% were at risk of
burnout. Self-directedness at secondary school and higher education, and
strategies for learning and assessment at higher education were protective
factors against academic burnout. However, secondary selfdirectedness has an
indirect effect on academic burnout mediated by self-directedness in the first
year of medical school. In addition, self-study during class period was a risk
factor for burnout. CONCLUSION: Our results support the premise that students
experience mental health problems from an early stage at medical school.
Empowering medical students to develop strategies for learning assessment and
self-direction will help them manage their learning and, consequently, promote
their well-being. Finally, we found that it is not academic performance that
influences burnout but the time dedicated to study.
PMID- 28425884
TI - A Brief Course on Clinical Communication Skills: A Multi- Centered Study.
AB - INTRODUCTION: This paper describes and analyses the results of a multicenter
course on clinical communication skills with the use of the learning in small
groups, patient actors and feedback. The aim of the course was to encourage
participants to develop a more effective clinical communication to recognize the
different manifestations of the same disease in different patients (disease
versus illness). MATERIAL AND METHODS: The course was applied to third and fourth
year medical students in three Brazilian universities and one university in
Portugal. The evaluation was performed using scales regarding the participants'
point of view, multiple choice questionnaire, a self-efficacy and attitudinal
questionnaire. RESULTS: The study was conducted in 69 participants at the four
universities. The overall evaluation of the course (from 1 - 5) was 4.70 (SD
0.494), the self-evaluation on participation was 4.07 (SD 0.671); and the
evaluation about the use of simulated patients 4.51 (SD 0.501). The multiple
choice questionnaire and self-efficacy scale showed significant improvement.
DISCUSSION: The course methods had an excellent evaluation by students regardless
of the context in which the course has been applied. Furthermore, it allowed an
improvement on the knowledge and attitude of students regarding clinical
communication. CONCLUSION: It was possible to develop a multi-centric learning
strategy for clinical communication with a high evaluation by students who came
from a Portuguese university in a cooperation project with teachers from
Brazilian universities.
PMID- 28425885
TI - An Objective Structured Clinical Exam to Assess Semiology Skills of Medical
Students.
AB - INTRODUCTION: Mastery of history taking and physical exam skills is a key
competence of medical students. Objective Structured Clinical Examinations are
the gold standard to assess these competencies, but their implementation in
Portugal is poorly documented. We describe the implementation and our seven years
experience with a high-stakes Objective Structured Clinical Examination to assess
these skills in the School of Medicine, University of Minho. MATERIAL AND
METHODS: Our Objective Structured Clinical Examination is in place since 2010 and
has been subject to continuous improvements, including the adoption of a standard
setting procedure and an increase in the number of stations. RESULTS: Grades in
our exam are well distributed and discriminate among students. History taking
grades are lower and have remained stable throughout the years while physical
examination scores have risen. The exam is reliable, with internal consistency
above 0.45 and a G-coefficient of 0.74. It is also feasible, with a total testing
time of approximately 20 hours for 140 students, and the involvement of 18
standardized patients and 18 faculty assessors. More importantly, it was able to
engage the students, who recognize its importance. DISCUSSION: The most important
validity criterion of our, and any Objective Structured Clinical Examination,
would be predictive validity,the ability to predict the performance of students
in the clinical context. CONCLUSION: Our approach to a high-stakes Objective
Structured Clinical Examination shows that it is feasible, reliable, valid and
fair and can be implemented with success in the Portuguese setting.
PMID- 28425886
TI - An Overview of Teaching Communication of Bad News in Medical School: Should a
Lecture be Adequate to Address the Topic?
AB - INTRODUCTION: Delivering bad news is very common in medical daily practice.
Several studies have shown a lack of effective communication skills amongst
medical students, particularly concerning how to deliver bad news. The SPIKES
protocol allows communicating bad news in a 6-step method. The aim of this study
is to investigate the perspective of students related to this subject. MATERIAL
AND METHODS: A 45 minute lecture "Breaking Bad News" was given to 160 students in
the fifth and sixth years of the Medicine course, using the SPIKES' protocol
training. After the lecture, an online survey was given to all students, and a
cross-sectional and descriptive analysis of data extracted from survey was
undertaken. RESULTS: Fifty-four students (21% of overall) answered the online
survey. Eighty three percent said that theme should have an important role in
their further daily medical practice, and most of students rated the physicians'
role as challenging. Sixty percent of students expressed that communicating bad
news was an integral part of the medical course curriculum. Regarding the SPIKES'
protocol, 48% felt that the first step would be the easiest to put in practice,
and 40% felt that the fifth step related to "Emotions" would be the most
difficult. DISCUSSION: In general, the students would like to gain competencies
in breaking bad news using a practical approach Conclusions: Students highly
valued theoretical and practical approaches in teaching of communication of bad
news. Therefore, we encourage a combination approach in pre-graduate medical
education.
PMID- 28425887
TI - Undergraduate Teaching in Geriatrics and Pediatrics in Portuguese Medical
Schools: An Observational Study.
AB - INTRODUCTION: Motivated by the contracting nature of the Portuguese age pyramid,
and thereby the ever increasing geriatric population, the aim of this study was
to compare the number of European Credit Transfer and Accumulation System Credits
dedicated to Geriatrics with Pediatrics in Portuguese Medical Schools. MATERIAL
AND METHODS: An observational, descriptive and cross-sectional study was
conducted and included six Portuguese Medical Schools that have six years of
training and a total of 360 credits. The study plans were obtained from the
medical schools' websites or requested. Schools were grouped in modular/classic
teaching methodology and the courses were categorized in mandatory/optional and
specific/related. The credits of Geriatrics and Pediatrics were compared.
RESULTS: Four schools had classical methodology and two had a modular one.
Overall, they had more credits dedicated to Pediatrics than Geriatrics. Three
schools offered mandatory courses specifically oriented to Geriatrics (1.5 - 8
credits) compared to all schools mandatory courses courses on Pediatrics (5.7 -
26.5 credits). The ratio of averages of mandatory specific courses
(Pediatrics/Geriatrics) was 12.4 in the classical and 1.5 in the modular group.
DISCUSSION: Pediatrics teaching has revealed to be superior to Geriatrics in all
categories. Based on our results, we consider the Portuguese Geriatrics'
undergraduate teaching sub-optimal. CONCLUSION: Nowadays, geriatric population is
quantitatively similar to pediatric population. Efforts should be made to
adequate Geriatrics teaching to our reality in order to provide a more adequate
health care to this age group.
PMID- 28425888
TI - [Satisfacao com o Internato Medico em Portugal].
AB - INTRODUCTION: In the last years, the global context of medical education and
Medical Residency programs in Portugal suffered substantial changes. The primary
objective of this study was to evaluate and characterize medical residents
satisfaction with medical residency programs in Portugal and to identify features
that could be improved. MATERIAL AND METHODS: We utilized as model the survey
Postgraduate Hospital Educational Environment Measure that has been developed in
the United Kingdom and is speci cally targeted to medical residents. The survey
was translated and adapted to the Portuguese reality. The survey was available
online during April and May of 2016. RESULTS: A total of 3456 responses were
obtained, corresponding to a response rate of 35%. Endocrinology/Nutrition,
Cardiology, Anesthesiology, Family Physician and Gastroenterology were the
specialties in which the degree of satisfaction was higher, while Forensic
Medicine, Medical Oncology, Internal Medicine, General Surgery and Pneumology
showed the lowest level of satisfaction. DISCUSSION: This study presented a high
response rate when compared to previous studies. Portuguese medical residents
presented high levels of satisfaction. Depending on year of medical residency,
region, type of specialty and type of hospital marked asymmetries were noticed.
CONCLUSION: The survey s results should constitute in the future a support tool
for the implementation of local and national measures relating to the medical
residency. It is advisable to regularly conduct satisfaction surveys to medical
residents.
PMID- 28425890
TI - Biomedical Simulation: Evolution, Concepts, Challenges and Future Trends.
AB - Biomedical simulation is an effective educational complement for healthcare
training, both at undergraduate and postgraduate level. It enables knowledge,
skills and attitudes to be acquired in a safe, educationally orientated and
efficient manner. In this context, simulation provides skills and experience that
facilitate the transfer of cognitive, psychomotor and proper communication
competences, thus changing behavior and attitudes, and ultimately improving
patient safety. Beyond the impact on individual and team performance, simulation
provides an opportunity to study organizational failures and improve system
performance. Over the last decades, simulation in healthcare had a slow but
steady growth, with a visible maturation in the last ten years. The simulation
community must continue to provide the core leadership in developing standards.
There is a need for strategies and policy development to ensure its coordinated
and cost-effective implementation, applied to patient safety. This paper reviews
the evolutionary movements of biomedical simulation, including a review of the
Portuguese initiatives and nationwide programs. For leveling knowledge and
standardize terminology, basic but essential concepts in clinical simulation,
together with some considerations on assessment, validation and reliability are
presented. The final sections discuss the current challenges and future
initiatives and strategies, crucial for the integration of simulation programs in
the greater movement toward patient safety.
PMID- 28425889
TI - SOAP Methodology in General Practice/Family Medicine Teaching in Practical
Context.
AB - INTRODUCTION: Medical records in General Practice/Family Medicine are an
essential information support on the health status of the patient and a
communication document between health professionals. The development of
competencies in General Practice/Family Medicine during pre-graduation must
include the ability to make adequate medical records in practical context. As of
2012, medicine students at the University of Beira Interior have been performing
visits using the Subjective, Objective, Assessment and Plan - SOAP methodology,
with a performance evaluation of the visit, with the aim to check on which
Subjective, Objective, Assessment and Plan - SOAP aspects students reveal the
most difficulties in order to define improvement techniques and to correlate
patient grade with tutor evaluation. MATERIAL AND METHODS: Analysing the
evaluation data for the 2015 - 2016 school year at the General Practice/Family
Medicine visit carried out by fourth year students in medicine, comparing the
averages of each item in the Subjective, Objective, Assessment and Plan - SOAP
checklist and the patient evaluation. RESULTS: In the Subjective, Objective,
Assessment and Plan - SOAP, 29.7% of students are on the best grade quartile,
37.1% are on the best competencies quartile and 27.2% on the best patient grade
quartile. 'Evolution was verified/noted' received the worst grades in Subjective,
'Record of physical examination focused on the problem of the visit' received the
worst grades in Objective, 'Notes of Diagnostic reasoning / differential
diagnostic' received de worst grades in Assessment and 'Negotiation of aims to
achieve' received the worst grades in Plan. The best tutor evaluation is found in
'communication'. DISCUSSION: Only one single study evaluated student's
performance under examination during a visit, with similar results to the present
one and none addressed the patient's evaluation. CONCLUSION: Students revealed a
good performance in using the Subjective, Objective, Assessment and Plan - SOAP.
The findings represent the beginning of the introduction of the Subjective,
Objective, Assessment and Plan - SOAP to the students. This evaluation breaks
ground towards better ways to teach the most difficult aspects.
PMID- 28425891
TI - Teaching Psychology in Medicine: The Context, Methodologies and Doctor's
Professional Identity.
AB - INTRODUCTION: Teaching Psychology in medical curriculum has been the subject of
numerous dissertations that focus on the relevance of this knowledge for doctors,
at a general level. METHODS: A non-systematic review of the relevant literature,
particularly from the last decade, as well as national and international
recommendations addressing the need for integration of behavioural and social
sciences in medical training, was performed. RESULTS: The literature supports the
existence of preconceptions and negative attitudes towards the role of psychology
in medical education, demonstrated by research in various european and american
universities. The socio-cultural context, the different methodologies and
barriers experienced by teachers in medical education are listed and provide the
matrix for a more comprehensive discussion of the development of the doctor's
identity. CONCLUSION: Revisiting the experience of many years of teaching Medical
Psychology, it is considered that the process of integration of this curricular
area should occur horizontally and vertically throughout the course, stressing
the need for the pedagogical training of teachers. Concepts that arise from
personal reflection, adjusted to the reality of our education and the basic
principles that guide it, are elaborated in order to integrate the teaching of
Psychology in Medicine, emphasizing its importance and utility in the
competencies and abilities of future doctors.
PMID- 28425892
TI - The weakening of public health: A threat to population health and health care
system sustainability.
PMID- 28425893
TI - An examination of perceived health care availability and unmet health care need
in the City of Toronto, Ontario, Canada.
AB - OBJECTIVES: Although timely access to health care is a top priority, a burgeoning
body of research highlights the important role of neighbourhood environments on
unmet health care needs. This study aimed to examine an association between
perceptions of neighbourhood availability of health care services and experience
of unmet health care needs by gender in an urban city setting. METHODS: A total
of 2338 participants from the Neighbourhood Effects on Health and Well-being
(NEHW) study, between 25 and 64 years of age and dwelling in the City of Toronto,
Ontario, Canada, were included in the analyses. Four different logistic
regression models stratified by gender were used to examine the relationship
between neighbourhood health care availability and unmet health care need as well
as the impact of neighbourhood perception of health care availability on the
three different types of unmet needs. RESULTS: Perceived health care availability
was associated with higher likelihood of experiencing unmet health care needs in
both women and men (women = OR: 1.58, 95% CI: 1.09-2.28; men = OR: 1.92, 95% CI:
1.23-2.99). In addition, perceived health care availability was associated with
barrier- and wait times-related unmet health care need among women (OR: 1.83, 95%
CI: 1.13-2.97; OR: 1.93, 95% CI: 1.10-3.40 respectively), and personal choice-
and wait times-related unmet need among men (OR: 1.99, 95% CI: 1.10-3.58).
CONCLUSION: Individuals' perception of health care availability plays a crucial
role in the experience of unmet health care needs, suggesting the importance of
community-based policy development for improving physical conditions and the
social aspect of health care services.
PMID- 28425894
TI - Trends in smoking initiation in Canada: Does non-inclusion of young adults in
tobacco control strategies represent a missed opportunity?
AB - OBJECTIVES: Young adults face high prevalence rates for smoking. Recent evidence
suggests that many people initiate smoking during young adulthood, but little is
currently known about trends in initiation rates for this age group. METHODS: We
examined rates of initiation to first cigarette (FC) and daily smoking (DS)
during youth (5-17 years) and young adulthood (18-25 years) using nationally
representative data from the 2001, 2003, 2005, 2007, 2009, 2011 and 2013 cycles
of the Canadian Community Health Survey. We included all participants aged 25-26
to obtain seven mutually exclusive retrospective cohorts (n = 16 216). We used
logistic regression to examine four correlates of smoking - sex, education,
poverty status, and immigration status - and whether these factors modify time
trends in smoking. RESULTS: We found that initiation rates decreased during youth
(p < 0.001 for FC, p = 0.02 for DS) but not during young adulthood (p = 0.94 for
FC, p = 0.28 for DS). We found that men and respondents with fewer educational
credentials had relatively higher odds of initiating during young adulthood.
Trends in young adulthood stayed constant across subgroups. Trends in youth were
modified by education: participants who did not complete high school had no
decrease in initiation to FC and DS while those with post-secondary education
experienced a decrease in both outcomes. CONCLUSION: Tobacco control has failed
to address smoking initiation during young adulthood. Given the considerable
amount of initiation that occurs during this period, practitioners and policy
makers should direct more of their planning toward young adults.
PMID- 28425895
TI - Understanding sexual orientation and health in Canada: Who are we capturing and
who are we missing using the Statistics Canada sexual orientation question?
AB - OBJECTIVE: Public health research on inequalities in Canada depends heavily on
population data sets such as the Canadian Community Health Survey. While sexual
orientation has three dimensions - identity, behaviour and attraction -
Statistics Canada and public health agencies assess sexual orientation with a
single questionnaire item on identity, defined behaviourally. This study aims to
evaluate this item, to allow for clearer interpretation of sexual orientation
frequencies and inequalities. METHODS: Through an online convenience sampling of
Canadians >=14 years of age, participants (n = 311) completed the Statistics
Canada question and a second set of sexual orientation questions. RESULTS: The
single-item question had an 85.8% sensitivity in capturing sexual minorities,
broadly defined by their sexual identity, lifetime behaviour and attraction.
Kappa statistic for agreement between the single item and sexual identity was
0.89; with past year, lifetime behaviour and attraction were 0.39, 0.48 and 0.57
respectively. The item captured 99.3% of those with a sexual minority identity,
84.2% of those with any lifetime same-sex partners, 98.4% with a past-year same
sex partner, and 97.8% who indicated at least equal attraction to same-sex
persons. CONCLUSION: Findings from Statistics Canada surveys can be best
interpreted as applying to those who identify as sexual minorities. Analyses
using this measure will underidentify those with same-sex partners or attractions
who do not identify as a sexual minority, and should be interpreted accordingly.
To understand patterns of sexual minority health in Canada, there is a need to
incorporate other dimensions of sexual orientation.
PMID- 28425896
TI - A longitudinal cohort study examining determinants of overweight and obesity in
adulthood.
AB - OBJECTIVES: Adulthood overweight and obesity are multifaceted conditions
influenced by a combination of biological, environmental and socio-cultural
factors across the lifespan. Using a longitudinal study design, we aimed to
identify determinants of adulthood overweight and obesity, in relation to: 1)
childhood and life course factors, 2) geographical differences in air quality,
and 3) gender-specific factors, in a cohort followed from childhood into
adulthood. METHODS: Childhood data were acquired (1978-1986) from children
residing in four distinct Hamilton neighbourhoods (Ontario, Canada), including
air-quality assessments. Adulthood data were obtained (2006-2007) from
successfully retraced participants (n = 315) using comprehensive self
administered questionnaires. Multivariate logistic regressions were used to
evaluate determinants of adulthood overweight (BMI: 25-29.9 kg/m2) and obesity
(BMI: >=30). RESULTS: The prevalence of normal weight decreased drastically at
follow-up in adulthood, while that of overweight and obesity increased. Both
overweight and obesity in adulthood were associated with male gender and
occupational exposures to contaminants. Childhood residence in Hamilton
neighbourhoods with better air quality was associated with lesser odds of
adulthood overweight, whereas adulthood obesity was strongly linked to childhood
weight gain (overweight or obesity). Among females, childhood weight status
predicted overweight and obesity in adulthood, with always living in Hamilton,
lack of additional health insurance, negative self-appraisal and high blood
pressure during adulthood identified as other significant predictors. Among
males, prolonged occupational exposures to contaminants emerged as a unique
determinant of adulthood weight gain. CONCLUSION: Adulthood overweight and
obesity are associated with childhood and life course determinants, including
childhood weight status, residential air quality and occupational contaminant
exposures, in a gender-specific manner.
PMID- 28425897
TI - Diabetes among non-obese Filipino Americans: Findings from a large population
based study.
AB - OBJECTIVES: Filipino Americans form the second-largest Asian American and Pacific
Islanders subgroup. Growing evidence suggests that Filipino Americans have higher
rates of diabetes than non-Hispanic whites. The key objectives of this study are
1) to determine the prevalence of diabetes in non-obese Filipino Americans
compared to non-obese non-Hispanic whites, and 2) to identify risk factors for
diabetes in non-obese Filipino men and women. METHODS: Secondary analysis of
population-based data from combined waves (2007, 2009 and 2011) of the adult
California Health Interview Survey (CHIS). The study sample was restricted to non
obese Filipino Americans (n = 1629) and non-Hispanic whites (n = 72 072).
RESULTS: Non-obese Filipino Americans had more than twice the odds of diabetes
compared to non-Hispanic whites, even after correcting for several known risk
factors (OR = 2.80, p < 0.001). For non-obese Filipino men, older age, poverty,
cigarette smoking, and being overweight are associated with increased odds for
diabetes, while older age was the only factor associated with diabetes among
Filipina women. DISCUSSION: Diabetes prevention approaches need to be targeted
towards non-obese Filipino Americans, due to their high risk of diabetes.
PMID- 28425898
TI - Compliance with school nutrition policies in Ontario and Alberta: An assessment
of secondary school vending machine data from the COMPASS study.
AB - OBJECTIVES: We investigated the extent to which a sample of Ontario and Alberta
secondary schools are being compliant with their respective provincial nutrition
policies, in terms of the food and beverages sold in vending machines. METHODS:
This observational study used objective data on drinks and snacks from vending
machines, collected over three years of the COMPASS study (2012/2013-2014/2015
school years). Drink (e.g., sugar-containing carbonated/non-carbonated soft
drinks, sports drinks, etc.) and snack (e.g., chips, crackers, etc.) data were
coded by number of units available, price, and location of vending machine(s) in
the school. Univariate and bivariate analyses were undertaken using R version
3.2.3. In order to assess policy compliancy over time, nutritional information of
products in vending machines was compared to nutrition standards set out in P/PM
150 in Ontario, and those set out in the Alberta Nutrition Guidelines for
Children and Youth (2012) in Alberta. RESULTS: Results reveal a decline over time
in the proportion of schools selling sugar-containing carbonated soft drinks (9%
in 2012/2013 vs. 3% in 2014/2015), crackers (26% vs. 17%) and cake products (12%
vs. 5%) in vending machines, and inconsistent changes in the proportion selling
chips (53%, 67% and 65% over the three school years). Conversely, results
highlight increases in the proportion of vending machines selling chocolate bars
(7% vs. 13%) and cookies (21% vs. 40%) between the 2012/2013 and 2014/2015 school
years. CONCLUSION: Nutritional standard policies were not adhered to in the
majority of schools with respect to vending machines. There is a need for
investment in formal monitoring and evaluation of school policies, and the
provision of information and tools to support nutrition policy implementation.
PMID- 28425899
TI - Associations between the local food environment and the severity of food
insecurity among new families using community food security interventions in
Montreal.
AB - OBJECTIVES: To examine the association between the local food environment and the
severity of food insecurity among new families using community food security
interventions in Montreal. METHODS: In this cross-sectional study, we analyzed
baseline data from 785 adults aged 18-65 years enrolled in the evaluation of the
effects of organizations delivering community food security interventions in
Montreal. The dependent variable was household food insecurity, while the
independent variable was the local food environment, assessed through: location
of the most frequently used grocery store, distance between the participant's
residence and the community organization used, mode of transportation, walking
time to the most frequently used grocery store, satisfaction with the
acceptability and affordability of food available at the most frequently used
grocery store, and self-reported difficulties in accessing food. We used
polytomous logistic regression to estimate the association between household food
insecurity and the local food environment. In all the models, we coded food
security status in three categories: food security, moderate food insecurity and
severe food insecurity. The last group was used as a reference group. RESULTS:
Our data suggest that compared to households with severe food insecurity, those
with moderate food insecurity (OR = 0.43, 95% CI: 0.28-0.62) and those with food
security (OR = 0.13, 95% CI: 0.06-0.26) were less likely to report difficulties
in accessing food due to food affordability. Food-secure households also had
lower odds of reporting difficulties in accessing food due to transportation
constraints (OR = 0.18, 95% CI: 0.06-0.55) compared with severe food-insecure
households. Living a distance of between 1 and 2 km from the organization used
was significantly correlated with moderate food insecurity (OR = 1.80, 95% CI:
1.12-2.88). CONCLUSION: The local food environment is associated with severity of
household food insecurity among new families using community food security
interventions in Montreal. Future studies should study the relationship between
the local food environment and food insecurity across all dimensions of food
access.
PMID- 28425900
TI - ?
AB - OBJECTIFS: Cette etude vise a decrire la mobilisation des representations
ethnoculturelles par des agents et des gestionnaires de sante pour expliquer
l'echec partiel d'une politique de sante maternelle et discuter des consequences
potentielles de ces representations sur l'acces aux soins de sante des
populations.METHODES : Il s'agit d'une recherche qualitative de type socio
anthropologique mobilisant des entretiens approfondis, des discussions
informelles, des observations non participantes menees dans les centres de sante
et une analyse documentaire. Les entretiens ont ete menes aupres de 16 agents de
sante et de 10 gestionnaires. Les entretiens ont ete enregistres sous support
numerique et transcrits. L'etude s'est deroulee dans le district sanitaire de
Djibo au Burkina Faso.RESULTATS : L'identification ethnique, les coutumes
relatives a l'accouchement (pudeur, discretion, presence feminine), le statut
social des femmes (le faible pouvoir decisionnel), le nomadisme et l'organisation
sociale des populations et leurs resistances au changement sont eriges comme des
obstacles " culturels " a la politique de sante. L'usage largement repandu de ces
representations par les agents et les gestionnaires de sante contribue a
reprimander les populations et a masquer les facteurs structurels qui ont
pourtant une influence plus importante sur l'utilisation des services de sante
maternelle. CONCLUSION: Cette recherche met en lumiere le danger de l'usage
excessif des representations ethnoculturelles teintees de culturalisme dans les
pratiques et les politiques de sante publique en vehiculant des stereotypes a
l'egard de certains groupes de population. Pour comprendre le succes ou l'echec
des politiques sanitaires, il demeure important de considerer la qualite du
contact avec le systeme de sante, les facteurs structurels notamment les
capacites des menages a faire face aux depenses des soins de sante et des
distances entre les villages et les centres de sante. Ces elements permettraient
de mieux comprendre les disparites constatees a l'egard des indicateurs
d'utilisation des services de sante.
PMID- 28425901
TI - A systematic review and meta-analysis for the adverse effects, immunogenicity and
efficacy of Lyme disease vaccines: Guiding novel vaccine development.
AB - BACKGROUND: Lyme borreliosis (LB) is the most prevalent arthropod-borne
infectious disease in North America. Currently, no vaccine is available to
prevent LB in humans, although monovalent and multivalent vaccines have been
developed in the past. OBJECTIVE: The aim of the current study is to conduct a
systematic review and meta-analysis to evaluate and compare the findings from
these two classes of vaccines for their reactogenicity, immunogenicity and
efficacy, in the hope this may assist in the development of future vaccines.
METHODS: A search strategy was developed for online databases (PubMed, Ovid
MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme
disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical
trials were included to compare the results of the monovalent vaccines to those
of the multivalent one. Meta-analyses were conducted to evaluate the
reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for
LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the
monovalent vaccine from three different clinical trials at different dose
schedules. RESULTS: Incidence of redness (local adverse effect) and fever
(systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower
(p < 0.05) in individuals who received multivalent vaccines compared to those
receiving the monovalent one. Incidences of all other local and systemic adverse
effects were non-significantly lower in the multivalent vaccine compared to the
monovalent vaccines. Seroprotection was comparable among individuals who received
the two vaccine classes at the 30 MUg dose level. Efficacy in the prevention of
LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95%
CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for
the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26
0.63, p < 0.001). CONCLUSION: The current study further validates that the
monovalent and multivalent LB vaccines result in mild local side effects and self
limiting systemic adverse effects, with the multivalent vaccine slightly more
tolerable than the monovalent one. Both vaccine classes were similarly highly
immunogenic. A new vaccine with high safety standards, better efficacy, low cost,
and public acceptance is yet to be developed. Meanwhile, personal protection
limiting exposure to ticks is recommended.
PMID- 28425902
TI - Evidence for the benefits of food chain interventions on E. coli 0157:H7/NM
prevalence in retail ground beef and human disease incidence: A success story.
AB - OBJECTIVES: Human infection with Escherichia coli O157:H7/NM has historically
been associated with consumption of undercooked ground beef. The purpose of this
paper is to investigate the correlation of the decline in E. coli O157:H7/NM
infections in Canada with the introduction of control efforts in ground beef by
industry. METHODS: The human incidence of E. coli O157:H7/NM, prevalence in
ground beef and interventions from 1996 to 2014 were analyzed. Pathogen
prevalence data were obtained from federal government and industry surveillance
and inspection/compliance programs. A survey of the largest ground beef producers
in Canada was conducted to identify when interventions were implemented. RESULTS:
The incidence of E. coli O157:H7/NM infections in Canada declined from ~4
cases/100 000 to ~1 case/100 000 from 2000 to 2010. Verotoxigenic Escherichia
coli (VTEC) prevalence in ground beef sold at retail declined from about 30%
around the year 2000 to <2% since 2012. Other measures of the prevalence of E.
coli, VTEC, and E. coli O157:H7/NM in beef and ground beef also declined. The
number and types of interventions implemented in the major beef processing
establishments in Canada increased from 1996 to 2016. CONCLUSION: The observed
decline in human illnesses and pathogen levels in relation to retail meats was
associated with the introduction of control efforts by industry, federal and
provincial/territorial governments, and the general population. Industry-led
changes in beef processing along with the introduction of food safety policies,
regulations, and public education have led to improved food safety in Canada.
PMID- 28425903
TI - Improving linkage to HIV care at low-threshold STI/HIV testing sites: An
evaluation of the Immediate Staging Pilot Project in Vancouver, British Columbia.
AB - OBJECTIVES: The objective of the Immediate Staging Pilot Project (ISPP) was to
improve linkage to human immunodeficiency virus (HIV) care by increasing the
number of referrals made to HIV care, and to decrease the time between diagnosis
and linkage to care for newly diagnosed HIV clients. This pilot had the potential
to decrease HIV transmission at a population level by engaging clients in
treatment earlier. SETTING: The Bute Street Clinic and Health Initiative for Men
Clinic on Davie in Vancouver, British Columbia are low-threshold public health
facilities providing HIV/STI testing primarily to men who have sex with men
(MSM). INTERVENTION: To improve engagement of MSM in the cascade of HIV care, the
BC Centre for Disease Control implemented a 12-month ISPP in 2012 for clients
newly diagnosed with HIV. The pilot offered CD4 and viral load testing at the
time of diagnosis, implemented improved referral procedures and enhanced nursing
support for clients. OUTCOMES: Comparing linkage to care outcomes between a group
that received the standard of care (SOC) and an intervention group that received
immediate staging, the median linkage to care time decreased from 21.5 to 14.0
days respectively (p = 0.053). The referral rates to HIV care were 56.1% in the
SOC group and 94.1% in the intervention group (p < 0.001). CONCLUSION: Creating
best practices that include offering CD4 and viral load testing at the time of
diagnosis, enhanced nursing support and standardized referral processes has
facilitated an improvement in the quality of HIV services provided to MSM clients
attending low-threshold clinics.
PMID- 28425904
TI - "Testing is Healthy" TimePlay campaign: Evaluation of sexual health promotion
gamification intervention targeting young adults.
AB - OBJECTIVES: The objectives of the study were to 1) describe the implementation of
the "Testing is Healthy" campaign in four locations in British Columbia (BC) and
2) report process evaluation indicators for the campaign. PARTICIPANTS: Young
adults ages 20-29 years, the age group with the highest reported rates of
chlamydia and gonorrhea in BC. SETTINGS: Movie theatres located in Langley,
Burnaby, Coquitlam and Surrey, which are communities served by the Fraser Health
Authority (FHA) in BC. INTERVENTION: The FHA launched the campaign in 2014 and
2015 to bring down the prevalence of sexually transmitted infections (STIs) and
HIV in the region. The campaign used the Cineplex TimePlay platform to engage
moviegoers in answering STI/HIV-related questions, and to connect them to a
clinic finder on the BC Centre for Disease Control Sex Smart Resource (SSR)
website. TimePlay includes elements of gaming, is technology-based, and has been
a successful advertisement platform for consumer products and services. However,
this is the first time it has been used for sexual health promotion. The campaign
was evaluated for 1) reach, based on theatre attendance and TimePlay
participation, and 2) the effectiveness of connecting people to sexual health
information using SSR web analytics. OUTCOMES: In total, the campaign received
548 410 views and 77 149 plays. SSR web analytics showed a significant increase
in unique page views of the Clinic Finder page between the first and the second
campaign. IMPLICATIONS: The campaign reached a large population at a low cost and
was correlated with spikes in the unique page views for the Clinic Finder page.
PMID- 28425905
TI - More than words: Using visual graphics for community-based health research.
AB - With increased attention to knowledge translation and community engagement in the
applied health research field, many researchers aim to find effective ways of
engaging health policy and decision makers and community stakeholders. While
visual graphics such as graphs, charts, figures and photographs are common in
scientific research dissemination, they are less common as a communication tool
in research. In this commentary, I illustrate how and why visual graphics were
created and used to facilitate dialogue and communication throughout all phases
of a community-based health research study with a rural Indigenous community,
advancing community engagement and knowledge utilization of a research study. I
suggest that it is essential that researchers consider the use of visual graphics
to accurately communicate and translate important health research concepts and
content in accessible forms for diverse research stakeholders and target
audiences.
PMID- 28425906
TI - The Canadian dementia challenge: Ensuring optimal care and services for those at
risk or with dementia throughout the country.
AB - In the next 15 years, Canada is predicted to face a doubling in its population
affected by dementia. By 2038, an estimated 1.1 million Canadians will be
experiencing dementia, with unprecedented impact on social, economic and health
landscapes. In September 2015, the Canadian Academy of Health Sciences convened a
Forum, with the specific thematic goals of reviewing progress towards effective
dementia treatment and prevention, improved systems of care, advanced living and
built environments, and impactful technology developments. The orientation of the
Forum was to focus on potential solutions and advances in these areas. These
areas are integral to the goal of a national end-to-end program, where all
affected Canadians can be optimally supported in their communities and receive
quality of care - regardless of where they live or who they are.
PMID- 28425907
TI - Plain packaging policy: Preventing industry innovations.
AB - The pack is a marketing tool for the tobacco industry - its shape, colour, fonts,
descriptors and logos attract and mislead smokers. Health warnings on cigarette
packs serve as a knowledge reminder for smokers to quit smoking. Plain packaging
eliminates brand imagery elements from cigarette packs and has many benefits,
including the reduction of intention to smoke and the denormalization of smoking
behaviour. The tobacco industry has devised pack and product marketing
innovations that thwart the effectiveness of health warnings. Plain packaging
policy needs to address these innovations by restricting their use and preventing
them from undermining health warnings.
PMID- 28425908
TI - Rotavirus vaccine, breastfeeding, and other factors that could affect
susceptibility to gastroenteritis in young children.
PMID- 28425909
TI - Examining child sedentary behaviour in the context of children's current
multimedia environment.
PMID- 28425910
TI - Inclusion of a broader range of sexual orientations to strengthen the validity
and generalizability of findings.
PMID- 28425911
TI - A response to the use of respondent-driven sampling in urban Indigenous
populations.
PMID- 28425912
TI - How spatial release from masking may fail to function in a highly directional
auditory system.
AB - Spatial release from masking (SRM) occurs when spatial separation between a
signal and masker decreases masked thresholds. The mechanically-coupled ears of
Ormia ochracea are specialized for hyperacute directional hearing, but the
possible role of SRM, or whether such specializations exhibit limitations for
sound source segregation, is unknown. We recorded phonotaxis to a cricket song
masked by band-limited noise. With a masker, response thresholds increased and
localization was diverted away from the signal and masker. Increased separation
from 6 degrees to 90 degrees did not decrease response thresholds or improve
localization accuracy, thus SRM does not operate in this range of spatial
separations. Tympanal vibrations and auditory nerve responses reveal that
localization errors were consistent with changes in peripheral coding of signal
location and flies localized towards the ear with better signal detection. Our
results demonstrate that, in a mechanically coupled auditory system,
specialization for directional hearing does not contribute to source segregation.
PMID- 28425913
TI - Loss of Dnmt3a and Dnmt3b does not affect epidermal homeostasis but promotes
squamous transformation through PPAR-gamma.
AB - The DNA methyltransferase Dnmt3a suppresses tumorigenesis in models of leukemia
and lung cancer. Conversely, deregulation of Dnmt3b is thought to generally
promote tumorigenesis. However, the role of Dnmt3a and Dnmt3b in many types of
cancer remains undefined. Here, we show that Dnmt3a and Dnmt3b are dispensable
for homeostasis of the murine epidermis. However, loss of Dnmt3a-but not Dnmt3b
increases the number of carcinogen-induced squamous tumors, without affecting
tumor progression. Only upon combined deletion of Dnmt3a and Dnmt3b, squamous
carcinomas become more aggressive and metastatic. Mechanistically, Dnmt3a
promotes the expression of epidermal differentiation genes by interacting with
their enhancers and inhibits the expression of lipid metabolism genes, including
PPAR-gamma, by directly methylating their promoters. Importantly, inhibition of
PPAR-gamma partially prevents the increase in tumorigenesis upon deletion of
Dnmt3a. Altogether, we demonstrate that Dnmt3a and Dnmt3b protect the epidermis
from tumorigenesis and that squamous carcinomas are sensitive to inhibition of
PPAR-gamma.
PMID- 28425914
TI - Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at
early and late times after infection.
AB - Latent Epstein-Barr virus (EBV) infection is causally linked to several human
cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the
apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1
constitutively activates NFkappaB and is critical for survival of EBV
immortalized B cells. However, during early infection EBV induces rapid B cell
proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought
to define the mechanism of survival in the absence of LMP1/NFkappaB early after
infection. We used BH3 profiling to query mitochondrial regulation of apoptosis
and defined a transition from uninfected B cells (BCL-2) to early-infected (MCL
1/BCL-2) and immortalized cells (BFL-1). This dynamic change in B cell survival
mechanisms is unique to virus-infected cells and relies on regulation of MCL-1
mitochondrial localization and BFL-1 transcription by the viral EBNA3A protein.
This study defines a new role for EBNA3A in the suppression of apoptosis with
implications for EBV lymphomagenesis.
PMID- 28425915
TI - Competition between histone and transcription factor binding regulates the onset
of transcription in zebrafish embryos.
AB - Upon fertilization, the genome of animal embryos remains transcriptionally
inactive until the maternal-to-zygotic transition. At this time, the embryo takes
control of its development and transcription begins. How the onset of zygotic
transcription is regulated remains unclear. Here, we show that a dynamic
competition for DNA binding between nucleosome-forming histones and transcription
factors regulates zebrafish genome activation. Taking a quantitative approach, we
found that the concentration of non-DNA-bound core histones sets the time for the
onset of transcription. The reduction in nuclear histone concentration that
coincides with genome activation does not affect nucleosome density on DNA, but
allows transcription factors to compete successfully for DNA binding. In
agreement with this, transcription factor binding is sensitive to histone levels
and the concentration of transcription factors also affects the time of
transcription. Our results demonstrate that the relative levels of histones and
transcription factors regulate the onset of transcription in the embryo.
PMID- 28425916
TI - Combined ALK and MDM2 inhibition increases antitumor activity and overcomes
resistance in human ALK mutant neuroblastoma cell lines and xenograft models.
AB - The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is
limited, highlighting the need to improve their effectiveness in these patients.
To this end, we sought to develop a combination strategy to enhance the antitumor
activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and
xenograft models expressing activated ALK. Herein, we report that combined
inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and
pro-apoptotic proteins. Consequently, this combination treatment synergistically
inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK
amplification or mutations in vitro, and resulted in complete and durable
responses in neuroblastoma xenografts derived from these cells. We further
demonstrate that concurrent inhibition of MDM2 and ALK was able to overcome
ceritinib resistance conferred by MYCN upregulation in vitro and in vivo.
Together, combined inhibition of ALK and MDM2 may provide an effective treatment
for TP53 wild-type neuroblastoma with ALK aberrations.
PMID- 28425918
TI - Rhein and polydimethylsiloxane functionalized carbon/carbon composites as
prosthetic implants for bone repair applications.
AB - A major issue in bone tissue engineering is the selection of biocompatible
materials for implants, to reduce unwanted inflammatory reactions and promote
cell adhesion. Bone tissue growth on suitable biomedical implants can shorten
recovery and hospitalization after surgery. Therefore, a method to improve tissue
implant integration and healing would be of scientific and clinical interest. In
this work, we permeated polydimethylsiloxane (PDMS) into carbon/carbon (C/C)
composites (PDMS-C/C) and then coated it with 4,5-dihydroxyanthraquinone-2
carboxylic acid (rhein) to create rhein-PDMS-C/C to increase its biocompatibility
and reduce the occurrence of inflammatory reactions. We measured in vitro
adhesion and proliferation of MC3T3-E1 cells and bacteria to evaluate the
biocompatibility and antimicrobial properties of C/C, PDMS-C/C, and rhein-PDMS
C/C. In vivo, x-ray and micro-CT evaluation three, six and nine weeks after
surgery revealed that rhein-PDMS-C/C was more effective than PDMS-C/C and C/C
composite in terms of antibacterial activity, cell adhesion and tissue growth.
Compared with C/C and PDMS-C/C, rhein-PDMS-C/C could be suitable for clinical
applications for bone tissue engineering.
PMID- 28425919
TI - Cell behavior of human mesenchymal stromal cells in response to silica/collagen
based xerogels and calcium deficient culture conditions.
AB - Herein, we aim to elucidate osteogenic effects of two silica-based xerogels with
different degrees of bioactivity on human bone-derived mesenchymal stromal cells
by means of scanning electron microscopy, quantitative PCR enhanced osteogenic
effects and the formation of an extracellular matrix which could be ascribed to
the sample with lower bioactivity. Given the high levels of bioactivity, the
cells revealed remarkable sensitivity to extremely low calcium levels of the
media. Therefore, additional experiments were performed to elucidate cell
behavior under calcium deficient conditions. The results refer to capacity of the
bone-derived stromal cells to overcome calcium deficiency even though
proliferation, migration and osteogenic differentiation capabilities were
diminished. One reason for the differences of the cellular response (on tissue
culture plates versus xerogels) to calcium deficiency seems to be the positive
effect of silica. The silica could be detected intracellularly as shown by time
of flight-secondary ion mass spectrometry after cultivation of primary cells for
21 days on the surfaces of the xerogels. Thus, the present findings refer to
different osteogenic differentiation potentials of the xerogels according to the
different degrees of bioactivity, and to the role of silica as a stimulator of
osteogenesis. Finally, the observed pattern of connexin-based hemichannel gating
supports the assumption that connexin 43 is a key factor for calcium-mediated
osteogenesis in bone-derived mesenchymal stromal cells.
PMID- 28425920
TI - Development of a fast Monte Carlo dose calculation system for online adaptive
radiation therapy quality assurance.
AB - Online adaptive radiation therapy (ART) based on real-time magnetic resonance
imaging represents a paradigm-changing treatment scheme. However, conventional
quality assurance (QA) methods based on phantom measurements are not feasible
with the patient on the treatment couch. The purpose of this work is to develop a
fast Monte Carlo system for validating online re-optimized tri-60Co IMRT adaptive
plans with both high accuracy and speed. The Monte Carlo system is based on dose
planning method (DPM) code with further simplification of electron transport and
consideration of external magnetic fields. A vendor-provided head model was
incorporated into the code. Both GPU acceleration and variance reduction were
implemented. Additionally, to facilitate real-time decision support, a C++ GUI
was developed for visualizing 3D dose distributions and performing various
analyses in an online adaptive setting. A thoroughly validated Monte Carlo code
(gPENELOPE) was used to benchmark the new system, named GPU-accelerated DPM with
variance reduction (gDPMvr). The comparison using 15 clinical IMRT plans
demonstrated that gDPMvr typically runs 43 times faster with only 0.5% loss in
accuracy. Moreover, gDPMvr reached 1% local dose uncertainty within 2.3 min on
average, and thus is well-suited for ART QA.
PMID- 28425917
TI - TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to
provide quality control in the antigen presentation pathway.
AB - Recently, we revealed that TAPBPR is a peptide exchange catalyst that is
important for optimal peptide selection by MHC class I molecules. Here, we asked
whether any other co-factors associate with TAPBPR, which would explain its
effect on peptide selection. We identify an interaction between TAPBPR and UDP
glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the
calnexin/calreticulin quality control cycle that is known to regenerate the
Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a
multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR,
in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class
I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities
the reglucosylation of the glycan on MHC class I molecules, promoting their
recognition by calreticulin. Our results suggest that in addition to being a
peptide editor, TAPBPR improves peptide optimisation by promoting peptide
receptive MHC class I molecules to associate with the peptide-loading complex.
PMID- 28425921
TI - Plasma Micro-RNA Alterations Appear Late in Pancreatic Cancer.
AB - OBJECTIVES: The aim of this research was to study whether plasma microRNAs
(miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing
prediagnostic plasma samples collected before a PC diagnosis. BACKGROUND: PC has
a poor prognosis due to late presenting symptoms and early metastasis.
Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in
a prediagnostic setting. METHODS: We first performed an initial screen using a
panel of 372 miRNAs in a retrospective case-control cohort that included early
stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis
were then measured in an early detection case-control cohort wherein plasma
samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19
9 (Ca 19-9) levels were measured in all samples for comparison. RESULTS: Our
initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15
candidate miRNAs that were differentially expressed in plasma samples at PC
diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which
outperformed Ca 19-9 in receiver-operating characteristics analysis. However,
none of the candidate miRNAs, individually or in combination, were significantly
altered in prediagnostic plasma samples from 67 future PC patients compared with
132 matched controls. In comparison, Ca 19-9 levels were significantly higher in
the cases at <5 years before diagnosis. CONCLUSION: Plasma miRNAs are altered in
PC patients at diagnosis, but the candidate miRNAs found in this study appear
late in the course of the disease and cannot be used for early detection of the
disease.
PMID- 28425922
TI - Detailed Follow-up Study of Pediatric Orofacial Granulomatosis Patients.
AB - OBJECTIVES: Orofacial granulomatosis (OFG) is a chronic inflammatory condition
affecting the orofacial area. Its connection to Crohn disease (CD) is debated.
Our aim was to describe a cohort of pediatric patients with OFG in detail, study
the long-term behavior of OFG, and evaluate factors predicting CD in patients
with OFG. METHODS: We invited patients diagnosed with OFG at 2 university
hospitals, Finland for a follow-up appointment. Patients (n = 29) were examined
by a dentist and an otorhinolaryngologist using a structural schema. Orofacial
findings were also recorded using digital photographing. Patients filled in
questionnaires about general health and special diets. Patients' nutrition was
evaluated from food records. The findings were compared between patients with OFG
only and OFG with CD. RESULTS: Patients with CD had more findings in the
orofacial area (total score for orofacial findings median 11) compared to
patients with OFG only (total score median 7.5). There was no statistically
significant difference in the type of lesions between these groups, except the
upper lip was more often affected in patients with CD (n = 11) than in patients
with OFG only (n = 0). Most of the patients had normal otorhinolaryngological
findings. All patients with elevated anti-Saccharomyces cerevisiae antibody A
levels had CD (n = 6) and they presented with more orofacial findings (total
score) than patients with normal levels of anti-S cerevisiae antibody A (P =
0.0311). CONCLUSIONS: Long-term follow-up of pediatric-onset patients with OFG
shows good prognosis. Patients with OFG do not seem to have
otorhinolaryngological comorbidity. Anti-S cerevisiae antibody A may serve as a
factor to indicate the possible presence of underlying CD in patients with OFG,
but further studies are requested.
PMID- 28425923
TI - Connectivity Restoration in Wireless Sensor Networks via Space Network Coding.
AB - The problem of finding the number and optimal positions of relay nodes for
restoring the network connectivity in partitioned Wireless Sensor Networks (WSNs)
is Non-deterministic Polynomial-time hard (NP-hard) and thus heuristic methods
are preferred to solve it. This paper proposes a novel polynomial time heuristic
algorithm, namely, Relay Placement using Space Network Coding (RPSNC), to solve
this problem, where Space Network Coding, also called Space Information Flow
(SIF), is a new research paradigm that studies network coding in Euclidean space,
in which extra relay nodes can be introduced to reduce the cost of communication.
Unlike contemporary schemes that are often based on Minimum Spanning Tree (MST),
Euclidean Steiner Minimal Tree (ESMT) or a combination of MST with ESMT, RPSNC is
a new min-cost multicast space network coding approach that combines Delaunay
triangulation and non-uniform partitioning techniques for generating a number of
candidate relay nodes, and then linear programming is applied for choosing the
optimal relay nodes and computing their connection links with terminals.
Subsequently, an equilibrium method is used to refine the locations of the
optimal relay nodes, by moving them to balanced positions. RPSNC can adapt to any
density distribution of relay nodes and terminals, as well as any density
distribution of terminals. The performance and complexity of RPSNC are analyzed
and its performance is validated through simulation experiments.
PMID- 28425924
TI - Roles of Copper-Binding Proteins in Breast Cancer.
AB - Copper ions are needed in several steps of cancer progression. However, the
underlying mechanisms, and involved copper-binding proteins, are mainly elusive.
Since most copper ions in the body (in and outside cells) are protein-bound, it
is important to investigate what copper-binding proteins participate and, for
these, how they are loaded with copper by copper transport proteins. Mechanistic
information for how some copper-binding proteins, such as extracellular lysyl
oxidase (LOX), play roles in cancer have been elucidated but there is still much
to learn from a biophysical molecular viewpoint. Here we provide a summary of
copper-binding proteins and discuss ones reported to have roles in cancer. We
specifically focus on how copper-binding proteins such as mediator of cell
motility 1 (MEMO1), LOX, LOX-like proteins, and secreted protein acidic and rich
in cysteine (SPARC) modulate breast cancer from molecular and clinical aspects.
Because of the importance of copper for invasion/migration processes, which are
key components of cancer metastasis, further insights into the actions of copper
binding proteins may provide new targets to combat cancer.
PMID- 28425925
TI - Evaluation of the Immunomodulatory Properties of Streptococcus suis and Group B
Streptococcus Capsular Polysaccharides on the Humoral Response.
AB - Streptococcus suis and group B Streptococcus (GBS) are encapsulated streptococci
causing septicemia and meningitis. Antibodies (Abs) against capsular
polysaccharides (CPSs) have a crucial protective role, but the
structure/composition of the CPS, including the presence of sialic acid, may
interfere with the generation of anti-CPS Ab responses. We investigated the
features of the CPS-specific Ab response directed against S. suis serotypes 2 and
14 and GBS serotypes III and V after infection or immunization with purified
native or desialylated CPSs in mice. Whereas S. suis-infected mice developed a
very low/undetectable CPS-specific IgM response, significant anti-CPS IgM titers
were measured in GBS-infected animals (especially for type III GBS). No isotype
switching was detected in S. suis- or GBS-infected mice. While the expression of
sialic acid was essential for the immunogenicity of purified GBS type III CPS,
this sugar was not responsible for the inability of purified S. suis types 2, 14
and GBS type V CPSs to induce a specific Ab response. Thus, other biochemical
criteria unrelated to the presence of sialic acid may be responsible for the
inaptitude of the host immune system to mount an effective response against
certain S. suis and GBS CPS types.
PMID- 28425926
TI - Chemical Source Localization Fusing Concentration Information in the Presence of
Chemical Background Noise.
AB - We present the estimation of a likelihood map for the location of the source of a
chemical plume dispersed under atmospheric turbulence under uniform wind
conditions. The main contribution of this work is to extend previous proposals
based on Bayesian inference with binary detections to the use of concentration
information while at the same time being robust against the presence of
background chemical noise. For that, the algorithm builds a background model with
robust statistics measurements to assess the posterior probability that a given
chemical concentration reading comes from the background or from a source
emitting at a distance with a specific release rate. In addition, our algorithm
allows multiple mobile gas sensors to be used. Ten realistic simulations and ten
real data experiments are used for evaluation purposes. For the simulations, we
have supposed that sensors are mounted on cars which do not have among its main
tasks navigating toward the source. To collect the real dataset, a special arena
with induced wind is built, and an autonomous vehicle equipped with several
sensors, including a photo ionization detector (PID) for sensing chemical
concentration, is used. Simulation results show that our algorithm, provides a
better estimation of the source location even for a low background level that
benefits the performance of binary version. The improvement is clear for the
synthetic data while for real data the estimation is only slightly better,
probably because our exploration arena is not able to provide uniform wind
conditions. Finally, an estimation of the computational cost of the algorithmic
proposal is presented.
PMID- 28425927
TI - Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E
Variants.
AB - Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic
HEV is an important cause of chronic hepatitis in immunocompromised patients. The
rapid identification of novel HEV variants and accumulating sequence information
has prompted significant changes in taxonomy of the family Hepeviridae. This
family includes two genera: Orthohepevirus, which infects terrestrial
vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there
are four species, A-D, with widely differing host range. Orthohepevirus A
contains the HEV variants infecting humans and its significance continues to
expand with new clinical information. We now recognize eight genotypes within
Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates
among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between
humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and
HEV8, which were recently identified in dromedary and Bactrian camels,
respectively. HEV7 is an example of a novel genotype that was found to have
significance to human health shortly after discovery. In this review, we
summarize recent developments in HEV molecular taxonomy, epidemiology and
evolution and describe the discovery of novel camel HEV genotypes as an
illustrative example of the changes in this field.
PMID- 28425929
TI - Contradictions and Promise for End-of-Life Communication among Family and
Friends: Death over Dinner Conversations.
AB - The free, open-access website called "Let's Get Together and Talk about Death",
or Death over Dinner (DoD), provides resources for initiating end-of-life
conversations with family and friends by taking the frightening-talking about
death-and transforming it into the familiar-a conversation over dinner. This
qualitative, descriptive study uses grounded theory and thematic analysis to
answer the following research question: How do friend and family groups
communicate about death and dying in DoD conversations? To answer this question,
52 dinner groups were recruited and conversations were conducted, which consisted
of a facilitator and volunteers. The facilitators were the researchers or
research assistants who allowed dinner participants to control the conversation
and identify topics of interest, and participants were free to share as much or
as little as they wanted. Our analysis revealed that family and friend groups
communicated similarly in that they talked about similar topics and used similar
communication strategies to discuss those topics. Three major themes emerged:
Desire for a good death, which juxtaposed people's perceptions of a "dreaded"
death with those of a "desirable" death; tactics for coping, which consisted of
the subthemes of humour to diffuse tension or deflect discomfort, spiritual
reassurance, and topic avoidance; and topics that elicit fear or uncertainty,
which consisted of the subthemes of organ and whole-body donation, hospice and
palliative care, wills and advance directives. Ultimately, however, participants
felt their experiences were positive and DoD shows promise as a tool for families
to engage in end-of-life conversations.
PMID- 28425928
TI - Porcine Circoviruses and Xenotransplantation.
AB - Allotransplantation and xenotransplantation may be associated with the
transmission of pathogens from the donor to the recipient. Whereas in the case of
allotransplantation the transmitted microorganisms and their pathogenic effect
are well characterized, the possible influence of porcine microorganisms on
humans is mostly unknown. Porcine circoviruses (PCVs) are common in pig breeds
and they belong to porcine microorganisms that still have not been fully
addressed in terms of evaluating the potential risk of xenotransplantation using
pig cells, tissues, and organs. Two types of PCVs are known: porcine circovirus
(PCV) 1 and PCV2. Whereas PCV1 is apathogenic in pigs, PCV2 may induce severe pig
diseases. Although most pigs are subclinically infected, we do not know whether
this infection impairs pig transplant functionality, particularly because PCV2 is
immunosuppressive. In addition, vaccination against PCV2 is able to prevent
diseases, but in most cases not transmission of the virus. Therefore, PCV2 has to
be eliminated to obtain xenotransplants from uninfected healthy animals. Although
there is evidence that PCV2 does not infect-at least immunocompetent-humans,
animals should be screened using sensitive methods to ensure virus elimination by
selection, Cesarean delivery, vaccination, or embryo transfer.
PMID- 28425930
TI - The Peculiar Glycolytic Pathway in Hyperthermophylic Archaea: Understanding Its
Whims by Experimentation In Silico.
AB - Mathematical models are key to systems biology where they typically describe the
topology and dynamics of biological networks, listing biochemical entities and
their relationships with one another. Some (hyper)thermophilic Archaea contain an
enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase
(GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3
phosphoglycerate omitting adenosine 5'-triphosphate (ATP) formation by substrate
level-phosphorylation via phosphoglycerate kinase. In this study we formulate
three hypotheses that could explain functionally why GAPN exists in these
Archaea, and then construct and use mathematical models to test these three
hypotheses. We used kinetic parameters of enzymes of Sulfolobus solfataricus (S.
solfataricus) which is a thermo-acidophilic archaeon that grows optimally between
60 and 90 degrees C and between pH 2 and 4. For comparison, we used a model of
Saccharomyces cerevisiae (S. cerevisiae), an organism that can live at moderate
temperatures. We find that both the first hypothesis, i.e., that the
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plus phosphoglycerate kinase
(PGK) route (the alternative to GAPN) is thermodynamically too much uphill and
the third hypothesis, i.e., that GAPDH plus PGK are required to carry the flux in
the gluconeogenic direction, are correct. The second hypothesis, i.e., that the
GAPDH plus PGK route delivers less than the 1 ATP per pyruvate that is delivered
by the GAPN route, is only correct when GAPDH reaction has a high rate and 1,3
bis-phosphoglycerate (BPG) spontaneously degrades to 3PG at a high rate.
PMID- 28425931
TI - Chocolate Consumption and Risk of Heart Failure: A Meta-Analysis of Prospective
Studies.
AB - Epidemiological studies have shown inconsistent findings on the association
between chocolate consumption and risk of heart failure (HF). We, therefore,
performed a meta-analysis of prospective studies to determine the role of
chocolate intake in the prevention of HF. We searched databases of PubMed, Web of
Science, and Scopus through December 2016 and scrutinized the reference lists of
relevant literatures to identify eligible studies. Study-specific hazard ratios
(HRs) and 95% confidence intervals (CIs) were aggregated using random effect
models. The dose-response relationship between chocolate consumption and incident
HF was also assessed. This meta-analysis is registered with PROSPERO, number
CRD42017054230. Five prospective studies with 106,109 participants were finally
included. Compared to no consumption of chocolate, the pooled HRs (95% CIs) of HF
were 0.86 (0.82-0.91) for low-to-moderate consumption (<7 servings/week) and 0.94
(0.80-1.09) for high consumption (>=7 servings/week). In dose-response meta
analysis, we detected a curve linear relationship between chocolate consumption
and risk of HF (p for nonlinearity = 0.005). Compared with non-consumption, the
HRs (95% CIs) of HF across chocolate consumption levels were 0.92 (0.88-0.97),
0.86 (0.78-0.94), 0.93 (0.85-1.03), and 1.07 (0.92-1.23) for 1, 3, 7, and 10
servings/week, respectively. In conclusion, chocolate consumption in moderation
may be associated with a decreased risk of HF.
PMID- 28425932
TI - Validation of a Novel Technique and Evaluation of the Surface Free Energy of
Food.
AB - Characterizing the physical properties of a surface is largely dependent on
determining the contact angle exhibited by a liquid. Contact angles on the
surfaces of rough and irregularly-shaped food samples are difficult to measure
using a contact angle meter (goniometer). As a consequence, values for the
surface energy and its components can be mismeasured. The aim of this work was to
use a novel contact angle measurement method, namely the snake-based ImageJ
program, to accurately measure the contact angles of rough and irregular shapes,
such as food samples, and so enable more accurate calculation of the surface
energy of food materials. In order to validate the novel technique, the contact
angles of three different test liquids on four different smooth polymer films
were measured using both the ImageJ software with the DropSnake plugin and the
widely used contact angle meter. The distributions of the values obtained by the
two methods were different. Therefore, the contact angles, surface energies, and
polar and dispersive components of plastic films obtained using the ImageJ
program and the Drop Shape Analyzer (DSA) were interpreted with the help of
simple linear regression analysis. As case studies, the superficial
characteristics of strawberry and endive salad epicarp were measured with the
ImageJ program and the results were interpreted with the Drop Shape Analyzer
equivalent according to our regression models. The data indicated that the ImageJ
program can be successfully used for contact angle determination of rough and
strongly hydrophobic surfaces, such as strawberry epicarp. However, for the
special geometry of droplets on slightly hydrophobic surfaces, such as salad
leaves, the program code interpolation part can be altered.
PMID- 28425933
TI - Study on the Rationality for Antiviral Activity of Flos Lonicerae Japonicae
Fructus Forsythiae Herb Chito-Oligosaccharide via Integral Pharmacokinetics.
AB - In the present study, the rationality for the antiviral effect (H1N1 virus) of
Flos Lonicerae Japonicae (FLJ, named JinYinHua)-Fructus forsythiae (FF, named
LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was
investigated. We found that the improvement of antiviral activity for four
preparations attributed to the enhancement of bioavailability for the FLJ-FF herb
couple in vivo, and that caffeic acid derivatives are the most important type of
components for antiviral activity. The anti-Influenza virus activity-half maximal
inhibitory concentration (IC50), not area under concentration (AUC) was
considered as the weighting factor for integrating the pharmacokinetics of
caffeic acid derivatives. It was found that the integral absorption, both in
vitro and in vivo, especially that in Shuang-Huang-Lian, can be improved
significantly by COS, an absorption enhancer based on tight junction. The results
indicated that the antiviral activity in four preparations improved by COS was
mainly attributed to the integral absorption enhancement of caffeic acid
derivatives.
PMID- 28425934
TI - Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow
Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological
Approaches.
AB - Particulate matter (PM) contains heavy metals that affect various cellular
functions and gene expression associated with a range of acute and chronic
diseases in humans. However, the specific effects they exert on the stem cells
remain unclear. Here, we report the effects of PM collected from the city of
Jeddah on proliferation, cell death, related gene expression and systems of
biological analysis in bone marrow mesenchymal stem cells (BM-MSCs), with the aim
of understanding the underlying mechanisms. PM2.5 and PM10 were tested in vitro
at various concentrations (15 to 300 ug/mL) and durations (24 to 72 h). PMs
induced cellular stress including membrane damage, shrinkage and death. Lower
concentrations of PM2.5 increased proliferation of BM-MSCs, while higher
concentrations served to decrease it. PM10 decreased BM-MSCs proliferation in a
concentration-dependent manner. The X-ray fluorescence spectrometric analysis
showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis
(IPA) and hierarchical clustering analyses demonstrated that heavy metals were
associated with signaling pathways involving cell stress/death, cancer and
chronic diseases. qRT-PCR results showed differential expression of the apoptosis
genes (BCL2, BAX); inflammation associated genes (TNF-alpha and IL-6) and the
cell cycle regulation gene (p53). We conclude that PM causes inflammation and
cell death, and thereby predisposes to chronic debilitating diseases.
PMID- 28425935
TI - Water Access, Sanitation, and Hygiene Conditions and Health Outcomes among Two
Settlement Types in Rural Far North Cameroon.
AB - The Far North region in Cameroon has been more heavily impacted by cholera than
any other region over the past decade, but very little has been done to study the
drivers of waterborne diseases in the region. We investigated the relationship
between water, sanitation, and hygiene (WASH) parameters, microbial and
antibiotic resistance (AR) contamination levels in drinking water, and health
outcomes using health survey and molecular analysis during June and July of 2014
in two settlement types (agro-pastoralist villages and transhumant pastoralist
camps). Quantitative polymerase chain reaction was used to determine fecal
contamination sources, enteric pathogens, and antibiotic resistance genes.
Ruminant-associated fecal contamination was widespread in both settlement types
(81.2%), with human-associated contamination detected in 21.7% of the samples.
Salmonella spp. (59.4%) and Shiga toxin-producing E. coli (stx1 44.9% and stx2
31.9%) were detected across all samples. Tetracycline resistance was found only
in village samples. A significant difference in diarrheal incidence within the
past 28 days among young children was found between camps (31.3%) and villages
(0.0%). Our findings suggest that water contamination may play an important role
in contributing to gastrointestinal illness, supporting the need for future
research and public health intervention to reduce gastrointestinal illness in the
area.
PMID- 28425936
TI - Genistein Ameliorates Ischemia/Reperfusion-Induced Renal Injury in a SIRT1
Dependent Manner.
AB - Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation
in clinical practice. Genistein, the main isoflavone found in soy products, is
known to possess a wide spectrum of biochemical and pharmacological activities.
However, the protective effect of genistein on renal I/R injury has not been well
investigated. In the current study, we explore whether genistein exhibits its
renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We
found the treatment of genistein significantly reduced renal I/R-induced cell
death, simultaneously stimulating renal cell proliferation. Meanwhile, SIRT1
expression was up-regulated following the administration of genistein in renal
region. Furthermore, pharmacological inhibition or shRNA-mediated depletion of
SIRT1 significantly reversed the protective effect of genistein on renal
dysfunction, cellular damage, apoptosis, and proliferation following I/R injury,
suggesting an indispensible role of the increased SIRT1 expression and activity
in this process. Meanwhile, the reduced p53 and p21 expression and increased PCNA
(Proliferating Cell Nuclear Antigen) expression were blocked after the depletion
of SIRT1 compared with the genistein treatment group in the renal I/R process.
Hence, our results provided further experimental basis for the potential use of
genistein for the treatment of kidney disease with deficiency of SIRT1 activity.
PMID- 28425937
TI - Gamma-Aminobutyric Acid Increases the Production of Short-Chain Fatty Acids and
Decreases pH Values in Mouse Colon.
AB - Gamma-Aminobutyric acid (GABA) could regulate physiological functions in the
gastrointestinal tract. The present study aimed to investigate the effect of GABA
on colon health in mice. The female Kunming mice were given GABA at doses of 5,
10, 20 and 40 mg/kg/d for 14 days. Afterwards, the short-chain fatty acids
(SCFAs) concentrations, pH values, colon index, colon length and weight of
colonic and cecal contents were determined to evaluate the effects of GABA on
colon health. The results showed that intake of GABA could increase the
concentrations of acetate, propionate, butyrate and total SCFAs in colonic and
cecal contents, as well as the weight of colonic and cecal contents. The colon
index and length of the 40 mg/kg/d GABA-treated group were significantly higher
than those of the control group (p < 0.05). In addition, decrease of pH values in
colonic and cecal contents was also observed. These results suggest that GABA may
improve colon health.
PMID- 28425938
TI - The Sodium Content of Processed Foods in South Africa during the Introduction of
Mandatory Sodium Limits.
AB - BACKGROUND: In June 2016, the Republic of South Africa introduced legislation for
mandatory limits for the upper sodium content permitted in a wide range of
processed foods. We assessed the sodium levels of packaged foods in South Africa
during the one-year period leading up to the mandatory implementation date of the
legislation. METHODS: Data on the nutritional composition of packaged foods was
obtained from nutrition information panels on food labels through both in-store
surveys and crowdsourcing by users of the HealthyFood Switch mobile phone app
between June 2015 and August 2016. Summary sodium levels were calculated for 15
food categories, including the 13 categories covered by the sodium legislation.
The percentage of foods that met the government's 2016 sodium limits was also
calculated. RESULTS: 11,065 processed food items were included in the analyses;
1851 of these were subject to the sodium legislation. Overall, 67% of targeted
foods had a sodium level at or below the legislated limit. Categories with the
lowest percentage of foods that met legislated limits were bread (27%), potato
crisps (41%), salt and vinegar flavoured snacks (42%), and raw processed sausages
(45%). About half (49%) of targeted foods not meeting the legislated limits were
less than 25% above the maximum sodium level. CONCLUSION: Sodium levels in two
thirds of foods covered by the South African sodium legislation were at or below
the permitted upper levels at the mandatory implementation date of the
legislation and many more were close to the limit. The South African food
industry has an excellent opportunity to rapidly meet the legislated
requirements.
PMID- 28425941
TI - Response to Comments by Vuksan V. et al., Nutrients 2017, 9, 398, Regarding an
Article by Solah V.A. et al., Nutrients 2017, 9, 149.
AB - n/a.
PMID- 28425940
TI - Circadian Clock, Cell Division, and Cancer: From Molecules to Organism.
AB - As a response to environmental changes driven by the Earth's axial rotation, most
organisms evolved an internal biological timer-the so called circadian clock
which regulates physiology and behavior in a rhythmic fashion. Emerging evidence
suggests an intimate interplay between the circadian clock and another
fundamental rhythmic process, the cell cycle. However, the precise mechanisms of
this connection are not fully understood. Disruption of circadian rhythms has a
profound impact on cell division and cancer development and, vice versa,
malignant transformation causes disturbances of the circadian clock. Conventional
knowledge attributes tumor suppressor properties to the circadian clock. However,
this implication might be context-dependent, since, under certain conditions, the
clock can also promote tumorigenesis. Therefore, a better understanding of the
molecular links regulating the physiological balance between the two cycles will
have potential significance for the treatment of cancer and associated disorders.
PMID- 28425942
TI - Seasonal Dynamics of Haptophytes and dsDNA Algal Viruses Suggest Complex Virus
Host Relationship.
AB - Viruses influence the ecology and diversity of phytoplankton in the ocean. Most
studies of phytoplankton host-virus interactions have focused on bloom-forming
species like Emiliania huxleyi or Phaeocystis spp. The role of viruses infecting
phytoplankton that do not form conspicuous blooms have received less attention.
Here we explore the dynamics of phytoplankton and algal viruses over several
sequential seasons, with a focus on the ubiquitous and diverse phytoplankton
division Haptophyta, and their double-stranded DNA viruses, potentially with the
capacity to infect the haptophytes. Viral and phytoplankton abundance and
diversity showed recurrent seasonal changes, mainly explained by hydrographic
conditions. By 454 tag-sequencing we revealed 93 unique haptophyte operational
taxonomic units (OTUs), with seasonal changes in abundance. Sixty-one unique
viral OTUs, representing Megaviridae and Phycodnaviridae, showed only distant
relationship with currently isolated algal viruses. Haptophyte and virus
community composition and diversity varied substantially throughout the year, but
in an uncoordinated manner. A minority of the viral OTUs were highly abundant at
specific time-points, indicating a boom-bust relationship with their host. Most
of the viral OTUs were very persistent, which may represent viruses that coexist
with their hosts, or able to exploit several host species.
PMID- 28425939
TI - Fructose Consumption in the Development of Obesity and the Effects of Different
Protocols of Physical Exercise on the Hepatic Metabolism.
AB - Fructose consumption has been growing exponentially and, concomitant with this,
the increase in the incidence of obesity and associated complications has
followed the same behavior. Studies indicate that fructose may be a carbohydrate
with greater obesogenic potential than other sugars. In this context, the liver
seems to be a key organ for understanding the deleterious health effects promoted
by fructose consumption. Fructose promotes complications in glucose metabolism,
accumulation of triacylglycerol in the hepatocytes, and alterations in the lipid
profile, which, associated with an inflammatory response and alterations in the
redox state, will imply a systemic picture of insulin resistance. However,
physical exercise has been indicated for the treatment of several chronic
diseases. In this review, we show how each exercise protocol (aerobic, strength,
or a combination of both) promote improvements in the obesogenic state created by
fructose consumption as an improvement in the serum and liver lipid profile (high
density lipoprotein (HDL) increase and decrease triglyceride (TG) and low-density
lipoprotein (LDL) levels) and a reduction of markers of inflammation caused by an
excess of fructose. Therefore, it is concluded that the practice of aerobic
physical exercise, strength training, or a combination of both is essential for
attenuating the complications developed by the consumption of fructose.
PMID- 28425944
TI - Erratum: Effect of Fibre Supplementation on Body Weight and Composition,
Frequency of Eating and Dietary Choice in Overweight Individuals Nutrients 2017,
9, 149.
AB - n/a.
PMID- 28425943
TI - Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a
High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers.
AB - Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders
exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis.
Although the aetiology of IBD is unknown, several factors coming from the adipose
tissue and skeletal muscles, such as cytokines, adipokines and myokines, were
suggested in the pathogenesis of ulcerative colitis; however, it has not been
extensively studied whether voluntary exercise can ameliorate that disorder. We
explored the effect of moderate exercise (i.e., voluntary wheel running) on the
disease activity index (DAI), colonic blood flow (CBF), plasma irisin and
adiponectin levels and real-time PCR expression of proinflammatory markers in
mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed
a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic
and microscopic colitis in sedentary SD mice was accompanied by a significant
fall in CBF, some increase in colonic tissue weight and a significant increase in
the plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6, monocyte
chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice,
colonic lesions were aggravated, colonic tissue weight increased and the plasma
TNF-alpha, IL-6, MCP-1, IL-1beta and leptin levels significantly increased.
Simultaneously, a significant decrease in the plasma irisin and adiponectin
levels was observed in comparison with SD mice (p < 0.05). Exercise significantly
decreased macroscopic and microscopic colitis, substantially increased CBF and
attenuated the plasma TNF-alpha, IL-6, MCP-1, IL-1beta and leptin levels while
raising the plasma irisin and the plasma and WAT concentrations of adiponectin in
HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in
HFD mice, possibly due to a fall in colonic microcirculation and an increase in
the plasma and mesenteric fat content of proinflammatory biomarkers; and (2)
voluntary physical activity can attenuate the severity of colonic damage in mice
fed a HFD through the release of protective irisin and restoration of plasma
adiponectin.
PMID- 28425945
TI - A Systematic Review: Costing and Financing of Water, Sanitation, and Hygiene
(WASH) in Schools.
AB - Despite the success of recent efforts to increase access to improved water,
sanitation, and hygiene (WASH) globally, approximately one-third of schools
around the world still lack adequate WASH services. A lack of WASH in schools can
lead to the spread of preventable disease and increase school absences,
especially among women. Inadequate financing and budgeting has been named as a
key barrier for integrating successful and sustainable WASH programs into school
settings. For this reason, the purpose of this review is to describe the current
knowledge around the costs of WASH components as well as financing models that
could be applied to WASH in schools. Results show a lack of information around
WASH costing, particularly around software elements as well as a lack of data
overall for WASH in school settings as compared to community WASH. This review
also identifies several key considerations when designing WASH budgets or
selecting financing mechanisms. Findings may be used to advise future WASH in
school programs.
PMID- 28425946
TI - Robot-Beacon Distributed Range-Only SLAM for Resource-Constrained Operation.
AB - This work deals with robot-sensor network cooperation where sensor nodes
(beacons) are used as landmarks for Range-Only (RO) Simultaneous Localization and
Mapping (SLAM). Most existing RO-SLAM techniques consider beacons as passive
devices disregarding the sensing, computational and communication capabilities
with which they are actually endowed. SLAM is a resource-demanding task. Besides
the technological constraints of the robot and beacons, many applications impose
further resource consumption limitations. This paper presents a scalable
distributed RO-SLAM scheme for resource-constrained operation. It is capable of
exploiting robot-beacon cooperation in order to improve SLAM accuracy while
meeting a given resource consumption bound expressed as the maximum number of
measurements that are integrated in SLAM per iteration. The proposed scheme
combines a Sparse Extended Information Filter (SEIF) SLAM method, in which each
beacon gathers and integrates robot-beacon and inter-beacon measurements, and a
distributed information-driven measurement allocation tool that dynamically
selects the measurements that are integrated in SLAM, balancing uncertainty
improvement and resource consumption. The scheme adopts a robot-beacon
distributed approach in which each beacon participates in the selection,
gathering and integration in SLAM of robot-beacon and inter-beacon measurements,
resulting in significant estimation accuracies, resource-consumption efficiency
and scalability. It has been integrated in an octorotor Unmanned Aerial System
(UAS) and evaluated in 3D SLAM outdoor experiments. The experimental results
obtained show its performance and robustness and evidence its advantages over
existing methods.
PMID- 28425947
TI - Deep Count: Fruit Counting Based on Deep Simulated Learning.
AB - Recent years have witnessed significant advancement in computer vision research
based on deep learning. Success of these tasks largely depends on the
availability of a large amount of training samples. Labeling the training samples
is an expensive process. In this paper, we present a simulated deep convolutional
neural network for yield estimation. Knowing the exact number of fruits, flowers,
and trees helps farmers to make better decisions on cultivation practices, plant
disease prevention, and the size of harvest labor force. The current practice of
yield estimation based on the manual counting of fruits or flowers by workers is
a very time consuming and expensive process and it is not practical for big
fields. Automatic yield estimation based on robotic agriculture provides a viable
solution in this regard. Our network is trained entirely on synthetic data and
tested on real data. To capture features on multiple scales, we used a modified
version of the Inception-ResNet architecture. Our algorithm counts efficiently
even if fruits are under shadow, occluded by foliage, branches, or if there is
some degree of overlap amongst fruits. Experimental results show a 91% average
test accuracy on real images and 93% on synthetic images.
PMID- 28425949
TI - An Efficient Distributed Compressed Sensing Algorithm for Decentralized Sensor
Network.
AB - We consider the joint sparsity Model 1 (JSM-1) in a decentralized scenario, where
a number of sensors are connected through a network and there is no fusion
center. A novel algorithm, named distributed compact sensing matrix pursuit
(DCSMP), is proposed to exploit the computational and communication capabilities
of the sensor nodes. In contrast to the conventional distributed compressed
sensing algorithms adopting a random sensing matrix, the proposed algorithm
focuses on the deterministic sensing matrices built directly on the real
acquisition systems. The proposed DCSMP algorithm can be divided into two
independent parts, the common and innovation support set estimation processes.
The goal of the common support set estimation process is to obtain an estimated
common support set by fusing the candidate support set information from an
individual node and its neighboring nodes. In the following innovation support
set estimation process, the measurement vector is projected into a subspace that
is perpendicular to the subspace spanned by the columns indexed by the estimated
common support set, to remove the impact of the estimated common support set. We
can then search the innovation support set using an orthogonal matching pursuit
(OMP) algorithm based on the projected measurement vector and projected sensing
matrix. In the proposed DCSMP algorithm, the process of estimating the common
component/support set is decoupled with that of estimating the innovation
component/support set. Thus, the inaccurately estimated common support set will
have no impact on estimating the innovation support set. It is proven that under
the condition the estimated common support set contains the true common support
set, the proposed algorithm can find the true innovation set correctly. Moreover,
since the innovation support set estimation process is independent of the common
support set estimation process, there is no requirement for the cardinality of
both sets; thus, the proposed DCSMP algorithm is capable of tackling the unknown
sparsity problem successfully.
PMID- 28425948
TI - Characterization of N-Acyl Homoserine Lactones in Vibrio tasmaniensis LGP32 by a
Biosensor-Based UHPLC-HRMS/MS Method.
AB - Since the discovery of quorum sensing (QS) in the 1970s, many studies have
demonstrated that Vibrio species coordinate activities such as biofilm formation,
virulence, pathogenesis, and bioluminescence, through a large group of molecules
called N-acyl homoserine lactones (AHLs). However, despite the extensive
knowledge on the involved molecules and the biological processes controlled by QS
in a few selected Vibrio strains, less is known about the overall diversity of
AHLs produced by a broader range of environmental strains. To investigate the
prevalence of QS capability of Vibrio environmental strains we analyzed 87 Vibrio
spp. strains from the Banyuls Bacterial Culture Collection (WDCM911) for their
ability to produce AHLs. This screening was based on three biosensors, which
cover a large spectrum of AHLs, and revealed that only 9% of the screened
isolates produced AHLs in the defined experimental conditions. Among these AHL
producing strains, Vibrio tasmaniensis LGP32 is a well-known pathogen of
bivalves. We further analyzed the diversity of AHLs produced by this strain using
a sensitive bioguided UHPLC-HRMS/MS approach (Ultra-High-Performance Liquid
Chromatography followed by High-Resolution tandem Mass Spectrometry) and we
identified C10-HSL, OH-C12-HSL, oxo-C12-HSL and C14:1-HSL as QS molecules. This
is the first report that documents the production of AHL by Vibrio tasmaniensis
LGP32.
PMID- 28425950
TI - Diversity Analysis and Bioresource Characterization of Halophilic Bacteria
Isolated from a South African Saltpan.
AB - Though intensive research has been channeled towards the biotechnological
applications of halophiles and other extremophilic microbes, these studies have
not been, by any means, exhaustive. Saline environments still offer a vast
diversity of microbes with potential to produce an array of natural products
which can only be unlocked by concerted research efforts. In this study, a
combination of culture and molecular approaches were employed to characterize
halophilic bacteria from saltpan water samples and profile their potential
biotechnological applications. Physicochemical analysis of the water samples
showed that pH was alkaline (pH 8.8), with a salinity of 12.8%. 16S rRNA gene
targeted amplicon analysis produced 10 bacterial phyla constituting of
Bacteroidetes (30.57%), Proteobacteria (15.27%), Actinobacteria (9.05%),
Planctomycetes (5.52%) and Cyanobacteria (3.18%). Eighteen strains were
identified using sequencing analysis of the culturable bacterial strains. From
these, the strains SP7 and SP9 were positive for cellulase production while the
strains SP4, SP8 and SP22 were positive for lipase production. Quantitative
enzyme assays showed moderate extracellular cellulase activity (1.95 U/mL) and
lipase activity (3.71 U/mL) by the isolate SP9 and SP4 respectively. Further, of
the six isolates, the isolate SP9 exhibited exploitable potential in the
bioremediation of hydrocarbon pollution as demonstrated by its fairly high
activity against benzanthracene (70% DCPIP reduction). Elucidation of the
isolates secondary metabolites showed the production of the molecules 2,3
butanediol, hexahydro-3-(2-methylpropyl)pyrrole[1,2a]pyrazine-1,4-dione,
aziridine, dimethylamine and ethyl acetate (GC-MS) and oxypurinol and 5
hydroxydecanoic acid (LC-MS), particularly by the isolate Salinivibrio sp. SP9.
Overall, the study showed that the isolated halophiles can produce secondary
metabolites with potential industrial and pharmaceutical application.
PMID- 28425951
TI - Modification of Natural Eudesmane Scaffolds via Mizoroki-Heck Reactions.
AB - The Mizoroki-Heck reaction was applied to substrates derived from isocostic and
ilicic acids, important sesquiterpene components of Dittrichia viscosa L. Greuter
that were extracted directly from plant material collected in Morocco. After
optimization of the metallo-catalysis conditions, various aryl-groups were
successfully introduced on the exocyclic double bond with an exclusive E
configuration and without racemization.
PMID- 28425953
TI - Cancer Chemotherapy Specific to Acidic Nests.
AB - The realization of cancer therapeutics specific to cancer cells with less of an
effect on normal tissues is our goal. Many trials have been carried out for this
purpose, but this goal is still far from being realized. It was found more than
80 years ago that solid cancer nests are acidified, but in vitro studies under
acidic conditions have not been extensively studied. Recently, in vitro
experiments under acidic conditions were started and anti-cancer drugs specific
to acidic areas have been identified. Many genes have been reported to be
expressed at a high level under acidic conditions, and such genes may be potent
targets for anti-cancer drugs specific to acidic nests. In this review article,
recent in vitro, in vivo, and clinical achievements in anti-cancer drugs with
marked efficacy under acidic conditions are summarized, and the clinical use of
anti-cancer drugs specific to acidic nests is discussed.
PMID- 28425952
TI - Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory
Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived
Neurotrophic Factor Levels-An Ex Vivo Study.
AB - Metformin, the popular anti-diabetic drug was shown to exert multiple biological
effects. The most recent metformin gained attention as an agent that mobilizes
endogenous progenitor cells and enhances regenerative potential of organisms, for
example by promoting neurogenesis. In the present study, we examined the role of
metformin on mouse olfactory ensheathing cells (mOECs) derived from animals
receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The
mOECs expanded ex vivo were characterized in terms of their cellular phenotype,
morphology, proliferative activity, viability and accumulation of oxidative
stress factors. Moreover, we determined the mRNA and protein levels of brain
derived neurotrophic factor (BDNF), distinguishing the secretion of BDNF by mOECs
in cultures and circulating serum levels of BDNF. The mOECs used in the
experiment were glial fibrillary acidic protein (GFAP) and p75 neurotrophin
receptor (p75NTR) positive and exhibited both astrocyte-like and non-myelin
Schwann cell-like morphologies. Our results revealed that the proliferation of
OECs derived from mice treated with metformin was lowered, when compared to
control group. Simultaneously, we noted increased cell viability, reduced
expression of markers associated with cellular senescence and a decreased amount
of reactive oxygen species. We observed increased mRNA expression of BDNF and its
down-stream genes. Obtained results indicate that metformin may exert
antioxidant, anti-apoptotic and senolytic action on OECs expanded ex vivo.
PMID- 28425955
TI - Homomorphic Filtering for Improving Time Synchronization in Wireless Networks.
AB - Wireless sensor networks are used to sample the environment in a distributed way.
Therefore, it is mandatory for all of the measurements to be tightly synchronized
in order to guarantee that every sensor is sampling the environment at the exact
same instant of time. The synchronization drift gets bigger in environments
suffering from temperature variations. Thus, this work is focused on improving
time synchronization under deployments with temperature variations. The working
hypothesis demonstrated in this work is that the clock skew of two nodes (the
ratio of the real frequencies of the oscillators) is composed of a multiplicative
combination of two main components: the clock skew due to the variations between
the cut of the crystal of each oscillator and the clock skew due to the different
temperatures affecting the nodes. By applying a nonlinear filtering, the
homomorphic filtering, both components are separated in an effective way. A
correction factor based on temperature, which can be applied to any
synchronization protocol, is proposed. For testing it, an improvement of the FTSP
synchronization protocol has been developed and physically tested under
temperature variation scenarios using TelosB motes flashed with the IEEE 802.15.4
implementation supplied by TinyOS.
PMID- 28425954
TI - Inherited Variation in Vitamin D Genes and Type 1 Diabetes Predisposition.
AB - The etiology and pathophysiology of type 1 diabetes remain largely elusive with
no established concepts for a causal therapy. Efforts to clarify genetic
susceptibility and screening for environmental factors have identified the
vitamin D system as a contributory pathway that is potentially correctable. This
review aims at compiling all genetic studies addressing the vitamin D system in
type 1 diabetes. Herein, association studies with case control cohorts are
presented as well as family investigations with transmission tests, meta-analyses
and intervention trials. Additionally, rare examples of inborn errors of vitamin
D metabolism manifesting with type 1 diabetes and their immune status are
discussed. We find a majority of association studies confirming a predisposing
role for vitamin D receptor (VDR) polymorphisms and those of the vitamin D
metabolism, particularly the CYP27B1 gene encoding the main enzyme for vitamin D
activation. Associations, however, are tenuous in relation to the ethnic
background of the studied populations. Intervention trials identify the specific
requirements of adequate vitamin D doses to achieve vitamin D sufficiency.
Preliminary evidence suggests that doses may need to be individualized in order
to achieve target effects due to pharmacogenomic variation.
PMID- 28425956
TI - Acceptable Risk Analysis for Abrupt Environmental Pollution Accidents in
Zhangjiakou City, China.
AB - Abrupt environmental pollution accidents cause considerable damage worldwide to
the ecological environment, human health, and property. The concept of acceptable
risk aims to answer whether or not a given environmental pollution risk exceeds a
societally determined criterion. This paper presents a case study on acceptable
environmental pollution risk conducted through a questionnaire survey carried out
between August and October 2014 in five representative districts and two counties
of Zhangjiakou City, Hebei Province, China. Here, environmental risk primarily
arises from accidental water pollution, accidental air pollution, and tailings
dam failure. Based on 870 valid questionnaires, demographic and regional
differences in public attitudes towards abrupt environmental pollution risks were
analyzed, and risk acceptance impact factors determined. The results showed
females, people between 21-40 years of age, people with higher levels of
education, public servants, and people with higher income had lower risk
tolerance. People with lower perceived risk, low-level risk knowledge, high-level
familiarity and satisfaction with environmental management, and without
experience of environmental accidents had higher risk tolerance. Multiple
logistic regression analysis indicated that public satisfaction with
environmental management was the most significant factor in risk acceptance,
followed by perceived risk of abrupt air pollution, occupation, perceived risk of
tailings dam failure, and sex. These findings should be helpful to local decision
makers concerned with environmental risk management (e.g., selecting target
groups for effective risk communication) in the context of abrupt environmental
accidents.
PMID- 28425957
TI - Investigating Surface and Near-Surface Bushfire Fuel Attributes: A Comparison
between Visual Assessments and Image-Based Point Clouds.
AB - Visual assessment, following guides such as the Overall Fuel Hazard Assessment
Guide (OFHAG), is a common approach for assessing the structure and hazard of
varying bushfire fuel layers. Visual assessments can be vulnerable to imprecision
due to subjectivity between assessors, while emerging techniques such as image
based point clouds can offer land managers potentially more repeatable
descriptions of fuel structure. This study compared the variability of estimates
of surface and near-surface fuel attributes generated by eight assessment teams
using the OFHAG and Fuels3D, a smartphone method utilising image-based point
clouds, within three assessment plots in an Australian lowland forest. Surface
fuel hazard scores derived from underpinning attributes were also assessed.
Overall, this study found considerable variability between teams on most visually
assessed variables, resulting in inconsistent hazard scores. Variability was
observed within point cloud estimates but was, however, on average two to eight
times less than that seen in visual estimates, indicating greater consistency and
repeatability of this method. It is proposed that while variability within the
Fuels3D method may be overcome through improved methods and equipment,
inconsistencies in the OFHAG are likely due to the inherent subjectivity between
assessors, which may be more difficult to overcome. This study demonstrates the
capability of the Fuels3D method to efficiently and consistently collect data on
fuel hazard and structure, and, as such, this method shows potential for use in
fire management practices where accurate and reliable data is essential.
PMID- 28425958
TI - Reactions of 5-Indolizyl Lithium Compounds with Some Bielectrophiles.
AB - Abstract: Indolizyl-5-lithium anions react with succinic and phtalic anhidrides
giving 1,4-keto acids, with oxallyl chloride giving 1,2-diketone, and with ethyl
pyruvate giving 1,2-hydroxyacid. However, with alpha-halocarbonyl compounds, they
react in different ways, forming the products of selective bromination at C-5
(with alpha-bromo ketones and esters of alpha-bromo acids) and 5-chloroacetyl
indolizines.
PMID- 28425959
TI - The Cost of Arbovirus Disease Prevention in Europe: Area-Wide Integrated Control
of Tiger Mosquito, Aedes albopictus, in Emilia-Romagna, Northern Italy.
AB - Aedes albopictus (tiger mosquito) has become the most invasive mosquito species
worldwide, in addition to being a well-known vector of diseases, with a proven
capacity for the transmission of chikungunya and dengue viruses in Europe as well
as the Zika virus in Africa and in laboratory settings. This research quantifies
the cost that needs to be provided by public-health systems for area-wide
prevention of arboviruses in Europe. This cost has been calculated by evaluating
the expenditure of the plan for Aedes albopictus control set up in the Emilia
Romagna region (Northern Italy) after a chikungunya outbreak occurred in 2007.
This plan involves more than 280 municipalities with a total of 4.2 million
inhabitants. Public expenditure for plan implementation in 2008-2011 was examined
through simple descriptive statistics. Annual expenditure was calculated to be
approximately ?1.3 per inhabitant, with a declining trend (from a total of ?7.6
million to ?5.3 million) and a significant variability at the municipality level.
The preventative measures in the plan included antilarval treatments (about 75%
of total expenditure), education for citizens and in schools, entomological
surveillance, and emergency actions for suspected viremias. Ecological factors
and the relevance of tourism showed a correlation with the territorial
variability in expenditure. The median cost of one antilarval treatment in public
areas was approximately ?0.12 per inhabitant. Organizational aspects were also
analyzed to identify possible improvements in resource use.
PMID- 28425961
TI - Rapid Texture Optimization of Three-Dimensional Urban Model Based on Oblique
Images.
AB - Seamless texture mapping is one of the key technologies for photorealistic 3D
texture reconstruction. In this paper, a method of rapid texture optimization of
3D urban reconstruction based on oblique images is proposed aiming at the
existence of texture fragments, seams, and inconsistency of color in urban 3D
texture mapping based on low-altitude oblique images. First, we explore
implementing radiation correction on the experimental images with a radiation
procession algorithm. Then, an efficient occlusion detection algorithm based on
OpenGL is proposed according to the mapping relation between the terrain
triangular mesh surface and the images to implement the occlusion detection of
the visible texture on the triangular facets as well as create a list of visible
images. Finally, a texture clustering algorithm is put forward based on Markov
Random Field utilizing the inherent attributes of the images and solve the energy
function minimization by Graph-Cuts. The experimental results display that the
method is capable of decreasing the existence of texture fragments, seams, and
inconsistency of color in the 3D texture model reconstruction.
PMID- 28425960
TI - Studying Lactoferrin N-Glycosylation.
AB - Lactoferrin is a multifunctional glycoprotein found in the milk of most mammals.
In addition to its well-known role of binding iron, lactoferrin carries many
important biological functions, including the promotion of cell proliferation and
differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic
protein. These functions differ among lactoferrin homologs in mammals. Although
considerable attention has been given to the many functions of lactoferrin, its
primary nutritional contribution is presumed to be related to its iron-binding
characteristics, whereas the role of glycosylation has been neglected. Given the
critical role of glycan binding in many biological processes, the glycan moieties
in lactoferrin are likely to contribute significantly to the biological roles of
lactoferrin. Despite the high amino acid sequence homology in different
lactoferrins (up to 99%), each exhibits a unique glycosylation pattern that may
be responsible for heterogeneity of the biological properties of lactoferrins. An
important task for the production of biotherapeutics and medical foods containing
bioactive glycoproteins is the assessment of the contributions of individual
glycans to the observed bioactivities. This review examines how the study of
lactoferrin glycosylation patterns can increase our understanding of lactoferrin
functionality.
PMID- 28425962
TI - Regulation of Ubiquitin Enzymes in the TGF-beta Pathway.
AB - The transforming growth factor-beta (TGF-beta) pathway has a tumor suppressor
role in normal and premalignant cells but promotes oncogenesis in advanced cancer
cells. Components of the pathway are tightly controlled by ubiquitin modifying
enzymes and aberrations in these enzymes are frequently observed to dysregulate
the pathway causing diseases such as bone disorders, cancer and metastasis. These
enzymes and their counterparts are increasingly being tested as druggable
targets, and thus a deeper understanding of the enzymes is required. This review
summarizes the roles of specific ubiquitin modifying enzymes in the TGF-beta
pathway and how they are regulated.
PMID- 28425963
TI - A Multi-Platform Optical Sensor for In Vivo and In Vitro Algae Classification.
AB - Differentiation among major algal groups is important for the ecological and
biogeochemical characterization of water bodies, and for practical management of
water resources. It helps to discern the taxonomic groups that are beneficial to
aquatic life from the organisms causing harmful algal blooms. An LED-induced
fluorescence (LEDIF) instrument capable of fluorescence, absorbance, and
scattering measurements; is used for in vivo and in vitro identification and
quantification of four algal groups found in freshwater and marine environments.
Aqueous solutions of individual and mixed dissolved biological pigments relevant
to different algal groups were measured to demonstrate the LEDIF's capabilities
in measuring extracted pigments. Different genera of algae were cultivated and
the cell counts of the samples were quantified with a hemacytometer and/or
cellometer. Dry weight of different algae cells was also measured to determine
the cell counts-to-dry weight correlations. Finally, in vivo measurements of
different genus of algae at different cell concentrations and mixed algal group
in the presence of humic acid were performed with the LEDIF. A field sample from
a local reservoir was measured with the LEDIF and the results were verified using
hemacytometer, cellometer, and microscope. The results demonstrated the LEDIF's
capabilities in classifying and quantifying different groups of live algae.
PMID- 28425964
TI - Enhancing the Responsivity of Uncooled Infrared Detectors Using Plasmonics for
High-Performance Infrared Spectroscopy.
AB - A lead zirconate titanate (PZT;Pb(Zr0.52Ti0.48)O3) layer embedded infrared (IR)
detector decorated with wavelength-selective plasmonic crystals has been
investigated for high-performance non-dispersive infrared (NDIR) spectroscopy. A
plasmonic IR detector with an enhanced IR absorption band has been designed based
on numerical simulations, fabricated by conventional microfabrication techniques,
and characterized with a broadly tunable quantum cascade laser. The enhanced
responsivity of the plasmonic IR detector at specific wavelength band has
improved the performance of NDIR spectroscopy and pushed the limit of detection
(LOD) by an order of magnitude. In this paper, a 13-fold enhancement in the LOD
of a methane gas sensing using NDIR spectroscopy is demonstrated with the
plasmonic IR detector.
PMID- 28425965
TI - Comparison of CPAP and HFNC in Management of Bronchiolitis in Infants and Young
Children.
AB - Continuous positive airway pressure (CPAP) has been used in infants with
bronchiolitis for decades. Recently, high flow nasal cannula (HFNC) therapy was
introduced We conducted a retrospective study of treatment with CPAP vs. HFNC
between 2013 and 2015, comparing the development in respiratory rate, fraction of
inspired oxygen (FiO2) and heart rate, treatment failure, duration of treatment,
and length of hospital stay. A sample size of 49 children were included. Median
age was 1.9 months. Median baseline pCO2 was 7.4 kPa in both groups, respiratory
rate per minute was 57 vs. 58 (CPAP vs. HFNC). Respiratory rate decreased faster
in the CPAP group (p < 0.05). FiO2 decreased in the CPAP group and increased in
the HFNC group during the first 12 h, whereafter it decreased in both groups. (p
< 0.01). Heart rate development was similar in both groups. Twelve children (55%)
changed systems from HFNC to CPAP due to disease progression. There was no
difference in length of treatment, hospital stay, or transmission to intensive
care unit between the groups. CPAP was more effective than HFNC in decreasing
respiratory rate (RR) and FiO2. No differences were observed in length of
treatment or complications. Further studies should be conducted to compare the
efficacy of the two treatments of bronchiolitis, preferably through prospective
randomized trials.
PMID- 28425966
TI - Endurance Training with or without Glucose-Fructose Ingestion: Effects on Lactate
Metabolism Assessed in a Randomized Clinical Trial on Sedentary Men.
AB - Glucose-fructose ingestion increases glucose and lactate oxidation during
exercise. We hypothesized that training with glucose-fructose would induce key
adaptations in lactate metabolism. Two groups of eight sedentary males were
endurance-trained for three weeks while ingesting either glucose-fructose (GF) or
water (C). Effects of glucose-fructose on lactate appearance, oxidation, and
clearance were measured at rest and during exercise, pre-training, and post
training. Pre-training, resting lactate appearance was 3.6 +/- 0.5 vs. 3.6 +/-
0.4 mg.kg-1.min-1 in GF and C, and was increased to 11.2 +/- 1.4 vs. 8.8 +/- 0.7
mg.kg-1.min-1 by exercise (Exercise: p < 0.01). Lactate oxidation represented
20.6% +/- 1.0% and 17.5% +/- 1.7% of lactate appearance at rest, and 86.3% +/-
3.8% and 86.8% +/- 6.6% during exercise (Exercise: p < 0.01) in GF and C,
respectively. Training with GF increased resting lactate appearance and oxidation
(Training * Intervention: both p < 0.05), but not during exercise (Training *
Intervention: both p > 0.05). Training with GF and C had similar effects to
increase lactate clearance during exercise (+15.5 +/- 9.2 and +10.1 +/- 5.9 mL.kg
1.min-1; Training: p < 0.01; Training * Intervention: p = 0.97). The findings of
this study show that in sedentary participants, glucose-fructose ingestion leads
to high systemic lactate appearance, most of which is disposed non-oxidatively at
rest and is oxidized during exercise. Training with or without glucose-fructose
increases lactate clearance, without altering lactate appearance and oxidation
during exercise.
PMID- 28425967
TI - A Simple and Specific Noncompetitive ELISA Method for HT-2 Toxin Detection.
AB - We developed an HT-2 toxin-specific simple ELISA format with a positive read-out.
The assay is based on an anti-immune complex (IC) scFv antibody fragment, which
is genetically fused with alkaline phosphatase (AP). The anti-IC antibody
specifically recognizes the IC between a primary anti-HT-2 toxin Fab fragment and
an HT-2 toxin molecule. In the IC ELISA format, the sample is added together with
the scFv-AP antibody to the ELISA plate coated with the primary antibody. After
15 min of incubation and a washing step, the ELISA response is read. A
competitive ELISA including only the primary antibody recognizes both HT-2 and T
2 toxins. The anti-IC antibody makes the assay specific for HT-2 toxin, and the
IC ELISA is over 10 times more sensitive compared to the competitive assay. Three
different naturally contaminated matrices: wheat, barley and oats, were used to
evaluate the assay performance with real samples. The corresponding limits of
detection were 0.3 ng/mL (13 ug/kg), 0.1 ng/mL (4 ug/kg) and 0.3 ng/mL (16
ug/kg), respectively. The IC ELISA can be used for screening HT-2 toxin
specifically and in relevant concentration ranges from all three tested grain
matrices.
PMID- 28425968
TI - Deciphering the Multifactorial Susceptibility of Mucosal Junction Cells to HPV
Infection and Related Carcinogenesis.
AB - Human papillomavirus (HPV)-induced neoplasms have long been considered to
originate from viral infection of the basal cell layer of the squamous mucosa.
However, this paradigm has been recently undermined by accumulating data
supporting the critical role of a discrete population of squamo-columnar (SC)
junction cells in the pathogenesis of cervical (pre)cancers. The present review
summarizes the current knowledge on junctional cells, discusses their high
vulnerability to HPV infection, and stresses the potential clinical/translational
value of the novel dualistic model of HPV-related carcinogenesis.
PMID- 28425970
TI - Aneurysm-Specific miR-221 and miR-146a Participates in Human Thoracic and
Abdominal Aortic Aneurysms.
AB - Altered microRNA expression is implicated in cardiovascular diseases. Our
objective was to determine microRNA signatures in thoracic aortic aneurysms
(TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal
aortic specimens. We evaluated the expression of fifteen selected microRNA in
human TAA and AAA operative specimens compared to controls. We observed
significant upregulation of miR-221 and downregulation of miR-1 and -133 in TAA
specimens. In contrast, upregulation of miR-146a and downregulation of miR-145
and -331-3p were found only for AAA specimens. Upregulation of miR-126 and -486
5p and downregulation of miR-30c-2*, -155, and -204 were observed in specimens of
TAAs and AAAs. The data reveal microRNA expression signatures unique to aneurysm
location and common to both thoracic and abdominal pathologies. Thus, changes in
miR-1, -29a, -133a, and -221 are involved in TAAs and miR-145, -146, and -331-3p
impact AAAs. This work validates prior studies on microRNA expression in
aneurysmal diseases.
PMID- 28425971
TI - rho0 Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and
Fluxes of Amino Acids.
AB - Solute carrier (SLC) transporters are a diverse group of membrane transporter
proteins that regulate the cellular flux and distribution of endogenous and
xenobiotic compounds. Post-translational modifications (PTMs), such as
ubiquitination, have recently emerged as one of the major regulatory mechanisms
in protein function and localization. Previously, we showed that SLC amino acid
transporters were on average 6-fold de-ubiquitinated and increased amino acid
levels were detected in rho0 cells (lacking mitochondrial DNA, mtDNA) compared to
parental cells. Here, we elucidated the altered functionality of SLC transporters
and their dynamic ubiquitination status by measuring the uptake of several
isotopically labeled amino acids in both human osteosarcoma 143B.TK- and rho0
cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid
transporters in rho0 cells were accompanied by an increased transport rate, which
leads to higher levels of amino acids in the cell. Finding SLC transport
enhancers is an aim of the pharmaceutical industry in order to compensate for
loss of function mutations in these genes. Thus, the ubiquitination status of SLC
transporters could be an indicator for their functionality, but evidence for a
direct connection between de-ubiquitination and transporter activity has to be
further elucidated.
PMID- 28425969
TI - The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and
Cognition Diseases.
AB - Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green
leafy vegetables, orange and yellow fruits that form the macular pigment of the
human eyes. It was hypothesized that they protect against visual disorders and
cognition diseases, such as age-related macular degeneration (AMD), age-related
cataract (ARC), cognition diseases, ischemic/hypoxia induced retinopathy, light
damage of the retina, retinitis pigmentosa, retinal detachment, uveitis and
diabetic retinopathy. The mechanism by which they are involved in the prevention
of eye diseases may be due their physical blue light filtration properties and
local antioxidant activity. In addition to their protective roles against light
induced oxidative damage, there are increasing evidences that L and Z may also
improve normal ocular function by enhancing contrast sensitivity and by reducing
glare disability. Surveys about L and Z supplementation have indicated that
moderate intakes of L and Z are associated with decreased AMD risk and less
visual impairment. Furthermore, this review discusses the appropriate consumption
quantities, the consumption safety of L, side effects and future research
directions.
PMID- 28425972
TI - The Impact of Hyposalivation on Quality of Life (QoL) and Oral Health in the
Aging Population of Al Madinah Al Munawarrah.
AB - Hyposalivation (HS) affects aging individuals by causing pain and discomfort in
the oral cavity. The aim here was to determine the impact of hyposalivation and
the saliva pH on the quality of life and caries status of geriatrics population.
A total of 138 male outpatients attending the Taibah University College of
Dentistry (TUCoD) dental clinic were included in the study. The saliva flow, pH,
Quality of Life (QoL), and caries status were recorded. The QoL was measured
using the Arabic version of the Oral Health Impact Profile-14 (OHIP-14), and the
caries status was recorded using the Decayed, Missed, Filled Teeth (DMFT) index.
The mean age was 67.5 years and 64% were classified as having hyposalivation. The
older respondents tended to have a lower saliva flow and pH compared to their
younger counterparts. There was a significant inverse association (p = 0.02)
between the caries status and mean saliva flow rate. There was also a significant
(p < 0.001) positive correlation between caries and the OHIP-14 scores
(Spearman's rho = 0.293). The prevalence of hyposalivation was relatively high
and there was an inverse relationship between the age, the saliva flow, and pH.
Those with more caries reported significantly poor QoL.
PMID- 28425973
TI - EDIM-TKTL1/Apo10 Blood Test: An Innate Immune System Based Liquid Biopsy for the
Early Detection, Characterization and Targeted Treatment of Cancer.
AB - Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the
innate immune system. Activated monocytes (macrophages) phagocytose unwanted
cells/cell fragments from the whole body including solid tissues. As they return
to the blood, macrophages can be used for a non-invasive detection of biomarkers,
thereby providing high sensitivity and specificity, because the intracellular
presence of biomarkers is due to an innate immune response. Flow cytometry
analysis of blood enables the detection of macrophages and phagocytosed
intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for
two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10
protein epitope is a characteristic of tumor cells with abnormal apoptosis and
proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose
metabolism (Warburg effect), which is concomitant with invasive growth/metastasis
and resistant to radical and apoptosis inducing therapies. The detection of Apo10
and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%)
detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1
represents a drugable target, the EDIM based detection of TKTL1 enables a
targeted cancer therapy using the vitamin derivatives oxythiamine or benfo
oxythiamine.
PMID- 28425975
TI - Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin
Thiazole Derivatives as alpha-Glucosidase Inhibitors.
AB - A series of novel isatin-thiazole derivatives were synthesized and screened for
their in vitro alpha-glucosidase inhibitory activity. These compounds displayed a
varying degree of alpha-glucosidase inhibitory activity with IC50 ranging from
5.36 +/- 0.13 to 35.76 +/- 0.31 MUm as compared to the standard drug acarbose
(IC50 = 817.38 +/- 6.27 MUm). Among the series, compound 6p bearing a hydroxyl
group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the
N1-positions of the 5-methylisatin displayed the highest inhibitory activity with
an IC50 value of 5.36 +/- 0.13 MUm. Molecular docking studies revealed the
existence of hydrophobic interaction, CH-pi interaction, arene-anion interaction,
arene-cation interaction, and hydrogen bond between these compounds and alpha
glucosidase enzyme.
PMID- 28425974
TI - On the Edge of Research and Technological Application: A Critical Review of
Electromethanogenesis.
AB - The conversion of electrical current into methane (electromethanogenesis) by
microbes represents one of the most promising applications of bioelectrochemical
systems (BES). Electromethanogenesis provides a novel approach to waste
treatment, carbon dioxide fixation and renewable energy storage into a chemically
stable compound, such as methane. This has become an important area of research
since it was first described, attracting different research groups worldwide.
Basics of the process such as microorganisms involved and main reactions are now
much better understood, and recent advances in BES configuration and electrode
materials in lab-scale enhance the interest in this technology. However, there
are still some gaps that need to be filled to move towards its application. Side
reactions or scaling-up issues are clearly among the main challenges that need to
be overcome to its further development. This review summarizes the recent
advances made in the field of electromethanogenesis to address the main future
challenges and opportunities of this novel process. In addition, the present
fundamental knowledge is critically reviewed and some insights are provided to
identify potential niche applications and help researchers to overcome current
technological boundaries.
PMID- 28425976
TI - Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of
Cardiometabolic Genes in Newborn Rats.
AB - Infants born to women with diabetes or obesity are exposed to excess circulating
fuels during fetal heart development and are at higher risk of cardiac diseases.
We have previously shown that late-gestation diabetes, especially in conjunction
with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring.
This study investigated changes in genome-wide histone modifications in newborn
hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin
immunoprecipitation-sequencing revealed a differential peak distribution on gene
promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to
trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR
< 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the
gene-activating mark trimethylated lysine 4. Many of these genes (1) are
associated with the "metabolic process" in general and particularly with
"positive regulation of cholesterol biosynthesis" (FDR = 0.03); (2) overlap with
455 quantitative trait loci for blood pressure, body weight, serum cholesterol
(all, FDR < 0.1); and (3) are linked to cardiac disease
susceptibility/progression, based on disease ontology analyses and scientific
literature. These results indicate that maternal HF-diet changes the cardiac
histone signature in offspring suggesting a fuel-mediated epigenetic
reprogramming of cardiac tissue in utero.
PMID- 28425977
TI - Prospective Analysis of the Influence of Sport and Educational Factors on the
Prevalence and Initiation of Smoking in Older Adolescents from Croatia.
AB - The prevalence of smoking among Croatian adolescents is alarmingly high, but no
previous study has prospectively examined the sport- and academic-factors
associated with smoking and smoking initiation. This study aimed to prospectively
examine the associations between scholastic (educational) achievement and sport
factors and smoking in 16- to 18-year-old adolescents. This two-year prospective
cohort study included 644 adolescents who were 16 years of age at baseline (46%
females). Baseline testing was implemented at the beginning of the 3rd year of
high school (September 2014) when participants were 16 years old. Follow-up
testing was completed at the end of the fourth year of high school, which
occurred 20 months later. The evaluated predictor variables were educational
achievement- and sport-related-factors. The outcome variables were (i) smoking at
baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course
of the study. We assessed the associations between predictors and outcomes using
logistic regression models adjusted for age, gender, socioeconomic status, and
conflict with parents. The educational variables were consistently associated
with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95%
confidence interval (CI): 1.61-2.55; Follow-up: 1.59, 1.31-1.94), more frequent
absence from school (Baseline: OR: 1.40, 95% CI: 1.19-1.69; Follow-up: 1.30, 1.08
1.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10-2.89; Follow
up: 1.57, 1.03-2.41) in children who smoke. Adolescents who reported quitting
sports were at greater odds of being smokers (Baseline: 2.07, 1.31-3.32; Follow
up: 1.66, 1.09-2.56). Sport competitive achievement at baseline was protective
against smoking initiation during following two-year period (0.45, 0.21-0.91).
While the influence of the educational variables on smoking initiation has been
found to be established earlier; sport achievement was identified as a
significant protective factor against initiating smoking in older adolescents.
Results should be used in development of an anti-smoking preventive campaign in
older adolescents.
PMID- 28425978
TI - Validation of mid-infrared spectroscopy for macronutrient analysis of human milk.
AB - OBJECTIVE: Human milk has considerable variation in its composition. Hence, the
nutrient profile is only an estimate and can result in under- or over-estimation
of the intake of preterm infants. Mid-infrared (MIR) spectroscopy is an evolving
technique for analyzing human milk but needs validation before use in clinical
practice. STUDY DESIGN: Human milk samples from 35 mothers delivering at 35 weeks
to term gestation were analyzed for macronutrients by MIR spectroscopy and by
standard laboratory methods using Kjeldahl assay for protein, Mojonnier assay for
fat and high-pressure liquid chromatography assay for lactose. RESULTS: MIR
analysis of the macronutrients in human milk correlated well with standard
laboratory tests with intraclass correlation coefficients of 0.997 for fat, 0.839
for protein and 0.776 for lactose. Agreement between the two methods was
excellent for fat, and moderate for protein and lactose (P<0.001). CONCLUSIONS:
This methodological paper provides evidence that MIR spectroscopy can be used to
analyze macronutrient composition of human milk. Agreement between the
methodologies varies by macronutrient.
PMID- 28425979
TI - Factors leading to rehospitalization for tracheostomized and ventilator-dependent
infants through 2 years of age.
AB - OBJECTIVE: To identify factors leading to readmission for tracheostomized,
ventilator-dependent infants <2 years of age. STUDY DESIGN: Retrospective cohort
study of 117 tracheostomized, ventilator-dependent infants followed through 2
years of age. RESULTS: Home ventilator use (at hospital discharge, 6 and 12
months of age), inhaled steroid use (at 12 and 24 months of age), oxygen
dependence (at 6 and 12 months of age) and tracheostomy (at discharge, 6 and 12
months of age) were increased risks for rehospitalization. Equipment malfunction
throughout the first 2 years also contributed to readmissions. Viral infection,
with rhinovirus/enterovirus the most commonly identified pathogen, was the most
common etiology for rehospitalization. Diuretic use and initial comorbid
diagnoses were not associated with increased risk of rehospitalization.
CONCLUSION: The risk for rehospitalization for infants requiring tracheostomy and
ventilator support was affected by prolonged oxygen use, prolonged ventilator
dependence, inhaled steroid use and equipment malfunction, and was equally
distributed throughout the first 2 years of life.
PMID- 28425980
TI - Possible barriers for genetic counselors returning actionable genetic research
results across state lines.
PMID- 28425981
TI - Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding
our knowledge of genetic disease during fetal development.
AB - PurposeThe aim of this study was to determine the diagnostic yield of whole-exome
sequencing (WES) in fetuses with ultrasound anomalies that resulted in fetal
demise or pregnancy termination. The results were also utilized to aid in the
identification of candidate genes for fetal development and to expand the
clinical phenotype of known genetic conditions.MethodsWES was performed on
specimens from 84 deceased fetuses. Data were analyzed and final results were
classified into one of four categories: positive, possible, negative, and
candidate gene only. WES analysis was predominantly performed in fetus-parent
trios or quads (61%, n=52).ResultsOverall, 20% (n = 17) of cases were positive,
45% (n=38) were possible, 9% (n=7) had only candidate gene variants and 26% (n =
22) tested negative. The diagnostic yield for definitive findings for trio
analysis was 24% (n = 11) compared to 14% (n = 4) for singletons. The most
frequently reported ultrasound anomalies were central nervous system (37%, n =
31), hydrops/edema (36%, n = 30), and cardiovascular anomalies (31%, n =
26).ConclusionOur experience supports the use of WES to identify the molecular
etiology of fetal ultrasound anomalies, to identify candidate genes involved in
fetal development, and to expand our knowledge of the clinical phenotype of known
genetic conditions.
PMID- 28425982
TI - CDH1 germline mutations: different syndromes, same management?
PMID- 28425983
TI - Addressing a patient-controlled approach for genomic data sharing.
PMID- 28425984
TI - Withaferin-A kills cancer cells with and without telomerase: chemical,
computational and experimental evidences.
AB - Maintenance of telomere length is the most consistent attribute of cancer cells.
Tightly connected to their capacity to overcome replicative mortality, it is
achieved either by activation of telomerase or an Alternative mechanism of
Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been
shown to induce DNA damage signalling leading to senescence or apoptosis.
Telomerase inhibitors are considered as potential anticancer drugs but are
ineffective for ALT cancers (~15% of all cancers). Withaferin-A (Wi-A), a major
constituent of the medicinal plant, Withania somnifera (Ashwagandha), has been
shown to exert anti-tumour activity. However, its effect on either telomerase or
ALT mechanisms has not been investigated. Here, by using isogenic cancer cells
with/without telomerase, we found that Wi-A caused stronger cytotoxicity to ALT
cells. It was associated with inhibition of ALT-associated promyelocytic leukemia
nuclear bodies, an established marker of ALT. Comparative analyses of telomerase
positive and ALT cells revealed that Wi-A caused stronger telomere dysfunction
and upregulation of DNA damage response in ALT cells. Molecular computational and
experimental analyses revealed that Wi-A led to Myc-Mad mediated transcriptional
suppression of NBS-1, an MRN complex protein that is an essential component of
the ALT mechanism. The results suggest that Wi-A could be a new candidate drug
for ALT cancers.
PMID- 28425986
TI - P16INK4a upregulation mediated by TBK1 induces retinal ganglion cell senescence
in ischemic injury.
AB - Glaucoma is a leading cause of irreversible blindness worldwide that is
characterized by progressive retinal ganglion cell (RGC) death. However, RGC
senescence as a phase before RGC death, and the mechanism of RGC senescence
remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is
upregulated in acute IOP elevation-induced ischemic retinas mouse model.
Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16)
expression and RGC senescence. Upregulation of TBK1 via plasmid transfection
increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation. The Akt
inhibitor MK-2206 decreased the expression of p16 and Bmi1 serine
phosphorylation. A Bmi1 Ser316 mutation also attenuated TBK1-induced p16
upregulation. Finally, silencing of TBK1 via shRNA knockdown reduced the
expression of p16 as well as Akt and Bmi1 phosphorylation, reducing RGC
senescence in vivo. These data suggest that acute IOP elevation-induced ischemia
increases TBK1 expression, which then increases p16 expression through the Akt-
Bmi1 phosphorylation pathway. This study therefore elucidates a novel mechanism
whereby TBK1 regulates p16 expression and RGC senescence, suggesting a potential
novel treatment strategy for minimizing RGC senescence in retinal ischemia and
glaucoma.
PMID- 28425987
TI - Biological activity of tumor-treating fields in preclinical glioma models.
AB - Glioblastoma is the most common and aggressive form of intrinsic brain tumor with
a very poor prognosis. Thus, novel therapeutic approaches are urgently needed.
Tumor-treating fields (TTFields) may represent such a novel treatment option. The
aim of this study was to investigate the effects of TTFields on glioma cells, as
well as the functional characterization of the underlying mechanisms. Here, we
assessed the anti-glioma activity of TTFields in several preclinical models.
Applying TTFields resulted in the induction of cell death in a frequency- and
intensity-dependent manner in long-term glioma cell lines, as well as glioma
initiating cells. Cell death occurred in the absence of caspase activation, but
involved autophagy and necroptosis. Severe alterations in cell cycle progression
and aberrant mitotic features, such as poly- and micronucleation, preceded the
induction of cell death. Furthermore, exposure to TTFields led to reduced
migration and invasion, which are both biological hallmarks of glioma cells. The
combination of TTFields with irradiation or the alkylating agent, temozolomide
(TMZ), resulted in additive or synergistic effects, and the O6-methyl-guanine DNA
methyltransferase status did not influence the efficacy of TTFields. Importantly,
TMZ-resistant glioma cells were responsive to TTFields application, highlighting
the clinical potential of this therapeutic approach. In summary, our results
indicate that TTFields induce autophagy, as well as necroptosis and hamper the
migration and invasiveness of glioma cells. These findings may allow for a more
detailed clinical evaluation of TTFields beyond the clinical data available so
far.
PMID- 28425985
TI - The cellular senescence of leukemia-initiating cells from acute lymphoblastic
leukemia is postponed by beta-Arrestin1 binding with P300-Sp1 to regulate hTERT
transcription.
AB - Although we previously reported that the self-renewal of leukemia-initiating
cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by
beta-Arrestin1, a multiple-function protein, the cellular senescence is critical
for LICs fate and leukemia progress, and worthy for further investigation. Here
we found that depletion of beta-Arrestin1 extended the population doubling time
and the percentage of senile cells, the signatures of cellular senescence, of B
ALL LICs. Moreover, lack of beta-Arrestin1 enhanced the expression of proteins
(CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and
B-ALL-LICs-derived leukemic mice. Further results showed that loss of beta
Arrestin1 induced senescence of Reh cells through mediating hTERT-telomerase
telomere axis, which was reversed by BIBR1532, the telomerase activity inhibitor.
Importantly, depletion of beta-Arrestin1 decreased the binding of Sp1 to hTERT
promoter at the region of -28 to -36 bp. The anti-sense oligonucleotide of this
key region downregulated the transcription of hTERT and aggravated the senescence
of Reh cells. Further data demonstrated that the depleted beta-Arrestin1 reduced
the interaction of P300 with Sp1, thus to reduce Sp1 binding to hTERT promoter,
downregulate hTERT transcription, decrease telomerase activity, shorten telomere
length, and promote Reh cell senescence. Interestingly, the percentage of senile
cells in B-ALL LICs was decreased, which was negatively correlated to good
prognosis and beta-Arrestin1 mRNA expression in childhood B-ALL patients. Our
study shed a light on the senescence of B-ALL LICs and is regulated by beta
Arrestin1, providing the potential therapeutic target of leukemia by promoting
cellular senescence with a key region of hTERT promoter.
PMID- 28425989
TI - Marine litter: Sea change for plastic pollution.
PMID- 28425990
TI - Ronald Drever (1931-2017).
PMID- 28425992
TI - Ecology: In peril from a perfect pathogen.
PMID- 28425993
TI - Materials science: How to print glass.
PMID- 28425994
TI - Modulating the therapeutic response of tumours to dietary serine and glycine
starvation.
AB - The non-essential amino acids serine and glycine are used in multiple anabolic
processes that support cancer cell growth and proliferation (reviewed in ref. 1).
While some cancer cells upregulate de novo serine synthesis, many others rely on
exogenous serine for optimal growth. Restriction of dietary serine and glycine
can reduce tumour growth in xenograft and allograft models. Here we show that
this observation translates into more clinically relevant autochthonous tumours
in genetically engineered mouse models of intestinal cancer (driven by Apc
inactivation) or lymphoma (driven by Myc activation). The increased survival
following dietary restriction of serine and glycine in these models was further
improved by antagonizing the anti-oxidant response. Disruption of mitochondrial
oxidative phosphorylation (using biguanides) led to a complex response that could
improve or impede the anti-tumour effect of serine and glycine starvation.
Notably, Kras-driven mouse models of pancreatic and intestinal cancers were less
responsive to depletion of serine and glycine, reflecting an ability of activated
Kras to increase the expression of enzymes that are part of the serine synthesis
pathway and thus promote de novo serine synthesis.
PMID- 28425995
TI - Widespread movement of meltwater onto and across Antarctic ice shelves.
AB - Surface meltwater drains across ice sheets, forming melt ponds that can trigger
ice-shelf collapse, acceleration of grounded ice flow and increased sea-level
rise. Numerical models of the Antarctic Ice Sheet that incorporate meltwater's
impact on ice shelves, but ignore the movement of water across the ice surface,
predict a metre of global sea-level rise this century in response to atmospheric
warming. To understand the impact of water moving across the ice surface a broad
quantification of surface meltwater and its drainage is needed. Yet, despite
extensive research in Greenland and observations of individual drainage systems
in Antarctica, we have little understanding of Antarctic-wide surface hydrology
or how it will evolve. Here we show widespread drainage of meltwater across the
surface of the ice sheet through surface streams and ponds (hereafter 'surface
drainage') as far south as 85 degrees S and as high as 1,300 metres above sea
level. Our findings are based on satellite imagery from 1973 onwards and aerial
photography from 1947 onwards. Surface drainage has persisted for decades,
transporting water up to 120 kilometres from grounded ice onto and across ice
shelves, feeding vast melt ponds up to 80 kilometres long. Large-scale surface
drainage could deliver water to areas of ice shelves vulnerable to collapse, as
melt rates increase this century. While Antarctic surface melt ponds are
relatively well documented on some ice shelves, we have discovered that ponds
often form part of widespread, large-scale surface drainage systems. In a warming
climate, enhanced surface drainage could accelerate future ice-mass loss from
Antarctic, potentially via positive feedbacks between the extent of exposed rock,
melting and thinning of the ice sheet.
PMID- 28425996
TI - Glaciology: Ice-shelf stability questioned.
PMID- 28425998
TI - Drivers of salamander extirpation mediated by Batrachochytrium salamandrivorans.
AB - The recent arrival of Batrachochytrium salamandrivorans in Europe was followed by
rapid expansion of its geographical distribution and host range, confirming the
unprecedented threat that this chytrid fungus poses to western Palaearctic
amphibians. Mitigating this hazard requires a thorough understanding of the
pathogen's disease ecology that is driving the extinction process. Here, we
monitored infection, disease and host population dynamics in a Belgian fire
salamander (Salamandra salamandra) population for two years immediately after the
first signs of infection. We show that arrival of this chytrid is associated with
rapid population collapse without any sign of recovery, largely due to lack of
increased resistance in the surviving salamanders and a demographic shift that
prevents compensation for mortality. The pathogen adopts a dual transmission
strategy, with environmentally resistant non-motile spores in addition to the
motile spores identified in its sister species B. dendrobatidis. The fungus
retains its virulence not only in water and soil, but also in anurans and less
susceptible urodelan species that function as infection reservoirs. The combined
characteristics of the disease ecology suggest that further expansion of this
fungus will behave as a 'perfect storm' that is able to rapidly extirpate highly
susceptible salamander populations across Europe.
PMID- 28425999
TI - Three-dimensional printing of transparent fused silica glass.
AB - Glass is one of the most important high-performance materials used for scientific
research, in industry and in society, mainly owing to its unmatched optical
transparency, outstanding mechanical, chemical and thermal resistance as well as
its thermal and electrical insulating properties. However, glasses and especially
high-purity glasses such as fused silica glass are notoriously difficult to
shape, requiring high-temperature melting and casting processes for macroscopic
objects or hazardous chemicals for microscopic features. These drawbacks have
made glasses inaccessible to modern manufacturing technologies such as three
dimensional printing (3D printing). Using a casting nanocomposite, here we create
transparent fused silica glass components using stereolithography 3D printers at
resolutions of a few tens of micrometres. The process uses a photocurable silica
nanocomposite that is 3D printed and converted to high-quality fused silica glass
via heat treatment. The printed fused silica glass is non-porous, with the
optical transparency of commercial fused silica glass, and has a smooth surface
with a roughness of a few nanometres. By doping with metal salts, coloured
glasses can be created. This work widens the choice of materials for 3D printing,
enabling the creation of arbitrary macro- and microstructures in fused silica
glass for many applications in both industry and academia.
PMID- 28426000
TI - Scientific methods: Teach children to spot fake facts.
PMID- 28426001
TI - Remote epitaxy through graphene enables two-dimensional material-based layer
transfer.
AB - Epitaxy-the growth of a crystalline material on a substrate-is crucial for the
semiconductor industry, but is often limited by the need for lattice matching
between the two material systems. This strict requirement is relaxed for van der
Waals epitaxy, in which epitaxy on layered or two-dimensional (2D) materials is
mediated by weak van der Waals interactions, and which also allows facile layer
release from 2D surfaces. It has been thought that 2D materials are the only seed
layers for van der Waals epitaxy. However, the substrates below 2D materials may
still interact with the layers grown during epitaxy (epilayers), as in the case
of the so-called wetting transparency documented for graphene. Here we show that
the weak van der Waals potential of graphene cannot completely screen the
stronger potential field of many substrates, which enables epitaxial growth to
occur despite its presence. We use density functional theory calculations to
establish that adatoms will experience remote epitaxial registry with a substrate
through a substrate-epilayer gap of up to nine angstroms; this gap can
accommodate a monolayer of graphene. We confirm the predictions with
homoepitaxial growth of GaAs(001) on GaAs(001) substrates through monolayer
graphene, and show that the approach is also applicable to InP and GaP. The grown
single-crystalline films are rapidly released from the graphene-coated substrate
and perform as well as conventionally prepared films when incorporated in light
emitting devices. This technique enables any type of semiconductor film to be
copied from underlying substrates through 2D materials, and then the resultant
epilayer to be rapidly released and transferred to a substrate of interest. This
process is particularly attractive in the context of non-silicon electronics and
photonics, where the ability to re-use the graphene-coated substrates allows
savings on the high cost of non-silicon substrates.
PMID- 28426002
TI - Materials science: Crystals aligned through graphene.
PMID- 28426003
TI - A temperate rocky super-Earth transiting a nearby cool star.
AB - M dwarf stars, which have masses less than 60 per cent that of the Sun, make up
75 per cent of the population of the stars in the Galaxy. The atmospheres of
orbiting Earth-sized planets are observationally accessible via transmission
spectroscopy when the planets pass in front of these stars. Statistical results
suggest that the nearest transiting Earth-sized planet in the liquid-water,
habitable zone of an M dwarf star is probably around 10.5 parsecs away. A
temperate planet has been discovered orbiting Proxima Centauri, the closest M
dwarf, but it probably does not transit and its true mass is unknown. Seven Earth
sized planets transit the very low-mass star TRAPPIST-1, which is 12 parsecs
away, but their masses and, particularly, their densities are poorly constrained.
Here we report observations of LHS 1140b, a planet with a radius of 1.4 Earth
radii transiting a small, cool star (LHS 1140) 12 parsecs away. We measure the
mass of the planet to be 6.6 times that of Earth, consistent with a rocky bulk
composition. LHS 1140b receives an insolation of 0.46 times that of Earth,
placing it within the liquid-water, habitable zone. With 90 per cent confidence,
we place an upper limit on the orbital eccentricity of 0.29. The circular orbit
is unlikely to be the result of tides and therefore was probably present at
formation. Given its large surface gravity and cool insolation, the planet may
have retained its atmosphere despite the greater luminosity (compared to the
present-day) of its host star in its youth. Because LHS 1140 is nearby,
telescopes currently under construction might be able to search for specific
atmospheric gases in the future.
PMID- 28426005
TI - Antarctic ice shelf potentially stabilized by export of meltwater in surface
river.
AB - Meltwater stored in ponds and crevasses can weaken and fracture ice shelves,
triggering their rapid disintegration. This ice-shelf collapse results in an
increased flux of ice from adjacent glaciers and ice streams, thereby raising sea
level globally. However, surface rivers forming on ice shelves could potentially
export stored meltwater and prevent its destructive effects. Here we present
evidence for persistent active drainage networks-interconnected streams, ponds
and rivers-on the Nansen Ice Shelf in Antarctica that export a large fraction of
the ice shelf's meltwater into the ocean. We find that active drainage has
exported water off the ice surface through waterfalls and dolines for more than a
century. The surface river terminates in a 130-metre-wide waterfall that can
export the entire annual surface melt over the course of seven days. During
warmer melt seasons, these drainage networks adapt to changing environmental
conditions by remaining active for longer and exporting more water. Similar
networks are present on the ice shelf in front of Petermann Glacier, Greenland,
but other systems, such as on the Larsen C and Amery Ice Shelves, retain surface
water at present. The underlying reasons for export versus retention remain
unclear. Nonetheless our results suggest that, in a future warming climate,
surface rivers could export melt off the large ice shelves surrounding Antarctica
contrary to present Antarctic ice-sheet models, which assume that meltwater is
stored on the ice surface where it triggers ice-shelf disintegration.
PMID- 28426006
TI - Carbon markets: extend, don't limit.
PMID- 28426007
TI - Carbon markets: link with caution.
PMID- 28426009
TI - Global coalition chips away at neglected tropical diseases.
PMID- 28426010
TI - Doom and gloom won't save the world.
PMID- 28426011
TI - Track how technology is transforming work.
PMID- 28426012
TI - Correction.
PMID- 28426013
TI - Fake-drug crackdown, tackling misconduct and Europa's plumes.
PMID- 28426014
TI - French-election fears unite scientists in defence of liberal democracy.
PMID- 28426015
TI - French scientists focus on the big political picture.
PMID- 28426017
TI - Drivers gear up for world's first nanocar race.
PMID- 28426016
TI - Unravelling why shoelace knots fail.
PMID- 28426018
TI - Five hacks for digital democracy.
PMID- 28426019
TI - DNA's secret weapon against knots and tangles.
PMID- 28426020
TI - Social networks push runners to run further and faster than their friends.
PMID- 28426021
TI - US foreign aid saves money as well as lives.
PMID- 28426022
TI - Republican scientists negotiate the Trump era.
PMID- 28426023
TI - Infection: Brief encounter: UTI triggered by vaginal microbiota.
PMID- 28426024
TI - Prostate cancer: Targeting the core of resistance.
PMID- 28426025
TI - Modular low-light microscope for imaging cellular bioluminescence and
radioluminescence.
AB - Low-light microscopy methods are receiving increased attention as new
applications have emerged. One such application is to allow longitudinal imaging
of light-sensitive cells with no phototoxicity and no photobleaching of
fluorescent biomarkers. Another application is for imaging signals that are
inherently dim and undetectable using standard microscopy techniques, such as
bioluminescence, chemiluminescence or radioluminescence. In this protocol, we
provide instructions on how to build a modular low-light microscope (1-4 d) by
coupling two microscope objective lenses, back to back from each other, using
standard optomechanical components. We also provide directions on how to image
dim signals such as those of radioluminescence (1-1.5 h), bioluminescence (~30
min) and low-excitation fluorescence (~15 min). In particular, radioluminescence
microscopy is explained in detail, as it is a newly developed technique that
enables the study of small-molecule transport (e.g., radiolabeled drugs,
metabolic precursors and nuclear medicine contrast agents) by single cells
without perturbing endogenous biochemical processes. In this imaging technique, a
scintillator crystal (e.g., CdWO4) is placed in close proximity to the
radiolabeled cells, where it converts the radioactive decays into optical flashes
detectable using a sensitive camera. Using the image reconstruction toolkit
provided in this protocol, the flashes can be reconstructed to yield high
resolution images of the radiotracer distribution. With appropriate timing, the
three aforementioned imaging modalities may be performed together on a population
of live cells, allowing the user to perform parallel functional studies of cell
heterogeneity at the single-cell level.
PMID- 28426027
TI - Analysis of the germination proteins in Alicyclobacillus acidoterrestris spores
subjected to external factors.
AB - The presence of Alicyclobacillus acidoterrestris, a thermoacidophilic and spore
forming bacterium, in pasteurized acidic juices poses a serious problem for the
processing industry. Therefore, the use of other more effective techniques, such
as high hydrostatic pressure (HHP) and supercritical carbon dioxide (SCCD), is
considered for preserving juices in order to inactivate these bacteria, while
reducing the loss of nutrients and sensory quality of juices. On the other hand,
HHP and SCCD when combined with a moderately elevated temperature can induce
germination of bacterial spores, making them more vulnerable to inactivation. The
spore germination can be also induced by nutrients, such as L-alanine or a
mixture of asparagine, glucose, fructose and potassium ions (AGFK). The aim of
this work was to determine whether applying activating agents: HHP, SCCD and
nutrient germinants (L-alanine and the AGFK mixture), could influence the number
of spores which start to germinate and how this affects the proteins involved in
the spore germination. SDS-PAGE was used to resolve proteins isolated from the A.
acidoterrestris spores. The results that were obtained indicate that the
germination of A. acidoterrestris spores treated with HHP, SCCD and nutrient
germinants reflect the number of spores which start to germinate. The SDS-PAGE
data indicated changes in the level of selected proteins occurring when subjected
to the germination activating factors as well as noticeable differences in those
proteins' molecular weights.
PMID- 28426026
TI - Generation of multipotent induced cardiac progenitor cells from mouse fibroblasts
and potency testing in ex vivo mouse embryos.
AB - Here we describe a protocol to generate expandable and multipotent induced
cardiac progenitor cells (iCPCs) from mouse adult fibroblasts using forced
expression of Mesp1, Tbx5, Gata4, Nkx2.5 and Baf60c (MTGNB) along with activation
of Wnt and JAK/STAT signaling. This method does not use iPS cell factors and thus
differs from cell activation and signaling-directed (CASD) reprogramming to
cardiac progenitors. Our method is specific to direct CPC reprogramming, whereas
CASD reprogramming can generate various cell types depending on culture
conditions and raises the possibility of transitioning through a pluripotent cell
state. The protocol describes how to isolate and infect primary fibroblasts;
induce reprogramming and observe iCPC colonies; expand and characterize
reprogrammed iCPCs by immunostaining, flow cytometry and gene expression;
differentiate iCPCs in vitro into cardiac-lineage cells; and test the embryonic
potency of iCPCs via injection into the cardiac crescent of mouse embryos. A
scientist experienced in molecular cell biology and embryology can reproduce this
protocol in 12-16 weeks. iCPCs can be used for studying cardiac biology, drug
discovery and regenerative medicine.
PMID- 28426030
TI - 1,3-N,O-Complexes of late transition metals. Ligands with flexible bonding modes
and reaction profiles.
AB - 1,3-N,O-Chelating ligands are ubiquitous in nature owing to their occurrence as
alpha-chiral amino acids in metalloproteins. These structural units also display
diverse coordination modes, which lend themselves to applications in catalysis as
well as novel fundamental stoichiometric reactivity, including the activation of
inert bonds. This review comments on recent developments in N,O-ligated late
transition metal complexes with an emphasis on preparation, characterization, and
reactivity.
PMID- 28426033
TI - Quantification of Lewis acid induced Bronsted acidity of protogenic Lewis bases.
AB - Proton transfer promoted by the coordination of protogenic Lewis bases to a Lewis
acid is a critical step in catalytic transformations. Although the acidification
of water upon coordination to a Lewis acid has been known for decades, no
attempts have been made to correlate the Bronsted acidity of the coordinated
water molecule with Lewis acid strength. To probe this effect, the pKa's
(estimated error of 1.3 pKa units) in acetonitrile of ten protogenic Lewis bases
coordinated to seven Lewis acids containing Lewis acidities varying 70 kcal mol
1, were computed. To quantify Lewis acid strength, the ability to transfer a
hydride (hydride donor ability) from the respective main group hydride was used.
Coordination of a Lewis acid to water increased the acidity of the bound water
molecule between 20 and 50 pKa units. A linear correlation exhibiting a 2.6 pKa
unit change of the Lewis acid-water adduct per ten kcal mol-1 change in hydride
donor ability of the respective main group hydride was obtained. For the ten
protogenic Lewis bases studied, the coordinated protogenic Lewis bases were
acidified between 10 and 50 pKa units. On average, a ten kcal mol-1 change in
hydride donor ability of the respective main group hydride resulted in about a
2.8 pKa unit change in the Bronsted acidity of the Lewis acid-Lewis base adducts.
Since attempts to computationally investigate the pKa of main group dihydrogen
complexes were unsuccessful, experimental determination of the first reported pKa
of a main group dihydrogen complex is described. The pKa of H2-B(C6F5)3 was
determined to be 5.8 +/- 0.2 in acetonitrile.
PMID- 28426035
TI - Hierarchical BiOI nanostructures supported on a metal organic framework as
efficient photocatalysts for degradation of organic pollutants in water.
AB - Semiconductor-based photocatalysis is a green method for the removal of toxic
organic pollutants by decomposition into harmless products. However, traditional
single-component semiconductors are unable to reach high degradation efficiencies
due to excessive photo charge carrier recombination. The use of hybrid
nanocomposite photocatalysts is a promising strategy for overcoming this problem
by reducing recombination as well as ensuring that large amounts of solar energy
are harvested. Herein, a novel visible-light-active hybrid nanocomposite,
BiOI/MIL-88B(Fe), was successfully synthesized through a simple precipitation
method. In the BiOI/MIL-88B(Fe) composite, both BiOI and MIL-88B(Fe) have
improved charge carrier separation and reduced recombination via a simple Z
scheme mechanism. Photocatalytic degradation of the pollutant RhB was carried out
during irradiation of the as-synthesized composites with simulated solar light,
and the BiOI/MIL-88B(Fe) (2 wt%) composite was found to exhibit the highest
photocatalytic activity among the composites. In addition, colorless phenol and
ciprofloxacin (CIP) degradation experiments were also performed to confirm the
visible light photocatalytic performance of the BiOI/MIL-88B(Fe) hybrid
nanocomposite. Scavenger experiments, PL analysis, NBT transformations, and TA-PL
experiments all supported the proposed Z-scheme mechanism of the BiOI/MIL-88B(Fe)
composite photocatalyst. Moreover, simple separation from solution provides this
3D composite with good reusability and long-term stability.
PMID- 28426036
TI - Formation of the intermetalloid cluster [AgSn18]7- - the reactivity of coinage
metal NHC compounds towards [Sn9]4.
AB - In recent years the formation of intermetalloid clusters by reacting homoatomic
tetrel cluster anions with transition metal complexes has become a promising
synthetic route. Nevertheless a better understanding of the processes occurring
in solution is necessary. Here we present a series of novel polyanionic coinage
metal NHC Zintl clusters [NHCDippM(eta4-Sn9)]3- (M: Cu, Ag, Au; Dipp:
diisopropylphenyl) which are obtained at low temperatures from the reaction of
K4Sn9 with NHCDippMCl (M: Cu-Au) in liquid ammonia. For M = Ag a larger
intermetalloid AgI-bridged nonastannide dimer [(eta4-Sn9)Ag(eta1-Sn9)]7- is also
formed. The stepwise formation of the intermetalloid cluster [AgSn18]7- is
discussed and compared with that of previously reported intermetalloid stannides.
PMID- 28426037
TI - Medicinal plant extracts and plant-derived polyphenols with anthelmintic activity
against intestinal nematodes.
AB - Covering: 2001 up to the end of 2016Polyphenols comprise a structurally diverse
class of natural products. As the development of new anthelmintic drugs against
soil-transmitted helminthiases is an urgent need and polyphenols are widely used
in the treatment of nematode infections in traditional medicine and modern
science, we summarize the state of knowledge in the period of mainly 2001 up to
the end of 2016 on plant extracts with known polyphenolic composition and of
defined polyphenols, mainly from the classes of condensed and hydrolysable
tannins, flavonoids, and phenylpropanoids. The diverse biological activity
against different helminths and the underlying mechanisms are reviewed.
PMID- 28426038
TI - Evaluation of the DGT technique for selective measurement of aluminium and trace
metal concentrations in an acid drainage-impacted coastal waterway.
AB - The performance of DGT-Chelex, DGT-Metsorb and DGT-MBL (Chelex-Metsorb mixed
binding layer) with open and restricted diffusive layers for trace metal (Al, Cd,
Co, Cu, Mn, Ni, Pb, Zn) and oxyanion (As, Mo, Sb, V) measurements, was evaluated
in four natural waters with different pH (range 3.29-7.81). In moderately acidic
(pH ~ 5) and circumneutral (pH ~ 6.3) waters, all three binding layers measured
relatively similar concentrations of Al, while in more alkaline waters (pH ~ 8)
DGT-MBL measured higher concentrations than the other two binding layers. The
measurements of DGT-Chelex and DGT-MBL for Co, Cu, Ni, Pb and Zn, and DGT-Metsorb
and DGT-MBL for As, Sb and V were within 82-119% and not statistically different
(p > 0.05) over the pH range 5-8. Mn measurements by DGT-Chelex and DGT-MBL were
quite similar (95%) at pH 6.3, while DGT-MBL measured higher concentrations than
DGT-Chelex at other pHs. The ratios of measured concentrations with different
diffusive layers (Crestricted/Copen) were between 0.78 and 1.12 for all binding
layers and no statistical differences (p > 0.05) were observed, except for Al at
pH 7.81 and Cu at pH 6.28. DGT-MBL was comparable to DGT-Chelex for the
measurement of most trace metals, and to DGT-Metsorb for the measurement of most
oxyanions, over the pH range 5.05-7.81. Overall, DGT-MBL is superior to the other
tested binding layers because it can simultaneously measure cations and anions,
and accurately measure dissolved Al, across the greatest range of environmental
conditions.
PMID- 28426039
TI - Controlled synthesis of lanthanide-doped Gd2O2S nanocrystals with novel
excitation-dependent multicolor emissions.
AB - Developing multicolor-emitting materials has significant value in many research
fields such as displays, bioimaging, and information storage. The widely adopted
strategies to realize multicolor emission are tuning the material composition,
phase, and size. Herein, the emission color was continuously controlled from
yellow to pink by simply changing the excitation wavelength from 254 nm to 365 nm
for Tb3+/Eu3+ co-doped Gd2O2S NCs. The Gd2O2S NCs with different morphologies,
including nanoplate with various sizes and flower-like, were successfully
prepared by seed-mediated, Na+/Y3+ co-doped, and S concentration-tuned methods.
The results indicated that Na+ ions greatly promote the growth of Gd2O2S NCs and
Y3+ ions have an impact on their shape. Moreover, the PL intensity of the 2%Eu
doped flower-like Na/Y:Gd2O2S (F-NYG) NCs decreased by about 24.7%, 6.8%, and
5.1% under 254 nm, 316 nm, and 348 nm excitation, respectively; this is due to
less non-radiative relaxation paths above the excited state of Eu3+:5D0 at longer
excitation wavelength, which result in a decreased degree of the PL intensity
reduction.
PMID- 28426040
TI - Enhancement of the hole conducting effect of NiO by a N2 blow drying method in
printable perovskite solar cells with low-temperature carbon as the counter
electrode.
AB - In this article, we demonstrate for the first time a mesoscopic printable
perovskite solar cell (PSC) using NiO as the hole transporting material and low
temperature processed carbon as the counter electrode. A single deposition method
assisted by N2 blow drying was used for the deposition of MAPbI3 on a
TiO2/ZrO2/NiO screen-printed electrode. As the final step a low-temperature
processing (i.e. 75 degrees C) carbon counter layer was fabricated on MAPbI3 by
a blade coating method. It is found that the capping layer thickness of MAPbI3
has a significant effect on the device efficiency, especially when NiO is
introduced as a hole transporting material into the structure. Electrochemical
impedance spectroscopy demonstrates good charge transport characteristics for the
device with a thin MAPbI3 capping layer obtained by the N2 blow drying method.
Our best performing device demonstrated a remarkable photovoltaic performance
with a short-circuit current density (Jsc) of 22.38 mA cm-2, an open circuit
voltage (Voc) of 0.97 V, and a fill factor (FF) of 0.50 corresponding to a photo
conversion efficiency (PCE) of 10.83%. Moreover, the un-encapsulated device
exhibited advantageous stability over 1000 h in air in the dark.
PMID- 28426041
TI - Hydrocarbon conversion in the production of synthetic fuels: general discussion.
PMID- 28426042
TI - Antibodies to H2a and H2b histones from the sera of HIV-infected patients
catalyze site-specific degradation of these histones.
AB - Histones and their post-translational modifications have key roles in chromatin
remodeling and gene transcription. Besides intranuclear functions, histones act
as damage-associated molecules when they are released into the extracellular
space. Administration of histones to animals leads to systemic inflammatory and
toxic responses. Autoantibodies with enzymatic activities (abzymes) are
distinctive features of some autoimmune and viral diseases. Electrophoretically
homogeneous IgGs containing no canonical enzymes were isolated from the sera of
HIV-infected patients by chromatography on several affinity sorbents including
anti-histone Sepharose. In contrast to canonical proteases (trypsin,
chymotrypsin, proteinase K), IgGs from HIV-infected patients specifically
hydrolyzed only histones but not many other tested globular proteins. Using MALDI
mass spectrometry the sites of H2a and H2b histone cleavage by anti-histone IgGs
were determined for the first time. One cluster of H2a hydrolysis contains two
major (?) and four moderate (?) cleavage sites: 31-H?R?L?L?R?K G?N-38. One major
and two moderate sites of cleavage were revealed in the second cluster: 14
A?KSRS?SRA?G-22. The third cluster corresponding to the H2a C-terminal part
contains only five minor (?) sites of cleavage: 82-H?LQLAIRNDEELN?KLLG?RV?T?I
102. It was shown that two major and four moderate sites of cleavage were present
in the main cluster of H2b hydrolysis: 46-K?QvhpD?TgiS?SkA?M?GiM?N-63. Two
moderate sites of cleavage correspond to a relatively short 6-mer cluster: 12
K?GskK?A-17. The third relatively long 9-mer cluster contains one major and two
minor sites of H2b cleavage: 80-L?AHYN?KRS?T-88. In the nucleosome core particle,
most of the major and moderate cleavage sites are located at the H2a/H2b
interaction interface. Minor cleavage sites of H2a are involved in binding with
H3 in the nucleosome core. Two moderate cleavage sites of H2b and one major
cleavage site of H2a are located in the disordered N-terminal region interacting
with DNA. According to the crystal structure of the nucleosome core particle, all
identified cleavage sites are expected to affect H2a and H2b folding, nucleosome
assembly, and binding of H2a and H2b with DNA. The existence of H2a and H2b
hydrolyzing abzymes may be very important for the further understanding of
unknown possibilities of immune systems and biological functions of antibodies.
PMID- 28426043
TI - Silica-encapsulated gold nanoparticle dimers for organelle-targeted cellular
delivery.
AB - Silica-encapsulated gold nanoparticle dimers were self-assembled through a single
insertion process using capillary force and can be utilized as an advanced drug
delivery and sensing platform for organelle-targeting in cancer cells.
PMID- 28426044
TI - Lanthanide coordination complexes framed by sodium ions: slow relaxation of the
magnetization in the Dy(III) derivative.
AB - Using a new polydentate Schiff-base ligand (H3L) we isolated three new
tetranuclear isostructural lanthanide complexes with the general formula
[LnNa2(L)4(DMF)4(H2O)2(AcO)2].4DMF.2H2O [Ln = Dy (1), Ho (2), or Er (3)]. The
structural characterization of the complexes reveals that the Na+ ions are
coordinated in the structure which gives them a structure-directing role in the
molecule. The magnetic behavior of the systems was investigated by means of SQUID
magnetometry which revealed that complex 1 exhibits single molecule magnet
behavior at low temperatures which is enhanced by the application of a 2000 Oe
static magnetic field. We were able to extract an effective barrier of Ueff =
43(1) K, however, we show that the consideration of an Orbach relaxation
mechanism being the dominant is not always correct for lanthanides. On the
contrary, we elaborate how in this system the relaxation is caused by a
combination of a direct and a Raman process.
PMID- 28426045
TI - Enzyme-coated Janus nanoparticles that selectively bind cell receptors as a
function of the concentration of glucose.
AB - A method is proposed for controlling the number of nanoparticles bound to cell
membranes via RGDS peptide-integrin interactions. It consists of propelling
nanoparticles bearing the peptides with enzymes (glucose oxidase), which disrupts
biomolecular interactions as a function of the concentration of enzyme substrate
(glucose).
PMID- 28426046
TI - Multicomponent reaction through cooperative trio catalysis incorporating enamine,
Bronsted acid and metal Lewis acid catalysis: a concise route to access chromans.
AB - An atom-economical multicomponent cascade reaction of salicylaldehydes,
cyclohexanones and arylamines has been developed for the synthesis of three-ring
fused chromans. This reaction was achieved through cooperative enamine-metal
Lewis acid assisted Bronsted acid catalysis, furnishing the products in excellent
yields with good diastereoselectivity.
PMID- 28426047
TI - Selective construction of quaternary stereocentres in radical cyclisation
cascades triggered by electron-transfer reduction of amide-type carbonyls.
AB - Radical-radical cyclisation cascades, triggered by single-electron-transfer to
amide-type carbonyls using SmI2-H2O-LiBr, result in the selective construction of
quaternary carbon stereocentres. The cascades deliver tricyclic barbiturates with
four stereocentres in good yield and with excellent diastereocontrol.
PMID- 28426048
TI - Flavored black ginseng exhibited antitumor activity via improving immune function
and inducing apoptosis.
AB - The objective of this project was to examine saponin and carbohydrate conversion,
and to evaluate the antitumor activity of a novel ready-to-eat flavored black
ginseng (FBG). The results of chemical experiments showed that common saponins in
ginseng such as ginsenoside Re, Rg1, Rb1, etc., are almost completely converted
to rare saponins and aglycones such as ginsenoside Rg5, protopanaxadiol (PPD),
etc., and non-reducing sugars such as starch are almost completely degraded into
reducing sugars as affected by garlic juice and high temperature processing.
Furthermore, pharmacological experimental results showed that this novel FBG
could inhibit the growth of tumors in H22 tumor-bearing mice dose-dependently at
the dosage of 250, 500 and 1000 mg kg-1; meanwhile, the results of ELISA, H&E
staining, western blotting and qRT-PCR show that FBG could improve immune
function and induce tumor cell apoptosis.
PMID- 28426049
TI - A Pt-Co3O4-CD electrocatalyst with enhanced electrocatalytic performance and
resistance to CO poisoning achieved by carbon dots and Co3O4 for direct methanol
fuel cells.
AB - Highly efficient electrocatalysts remain huge challenges in direct methanol fuel
cells (DMFCs). Here, a Pt-Co3O4-CDs/C composite was fabricated as an anode
electrocatalyst with low Pt content (12 wt%) by using carbon dots (CDs) and Co3O4
nanoparticles as building blocks. The Pt-Co3O4-CDs/C composite catalyst shows a
significantly enhanced electrocatalytic activity (1393.3 mA mg-1 Pt), durability
(over 4000 s) and CO-poisoning tolerance. The superior catalytic activity should
be attributed to the synergistic effect of CDs, Pt and Co3O4. Furthermore, the Pt
Co3O4-CDs/C catalyst was integrated into a single cell, which exhibits a maximum
power density of 45.6 mW cm-2, 1.7 times the cell based on the commercial 20 wt%
Pt/C catalyst.
PMID- 28426050
TI - Expanding the morphology library of block copolymer self-assemblies with clews of
tubules.
AB - The morphology library of block copolymer (BCP) self-assemblies is limited,
especially as far as tubular structures are concerned. Here, the morphology of
clews of tubules is discovered for the first time by self-assembly of P4VP-b-PS
BCPs with both high asymmetry and very high molecular weight, which successfully
expands the morphology library of BCP self-assemblies.
PMID- 28426052
TI - Artificial molecular motors.
AB - Motor proteins are nature's solution for directing movement at the molecular
level. The field of artificial molecular motors takes inspiration from these tiny
but powerful machines. Although directional motion on the nanoscale performed by
synthetic molecular machines is a relatively new development, significant
advances have been made. In this review an overview is given of the principal
designs of artificial molecular motors and their modes of operation. Although
synthetic molecular motors have also found widespread application as (multistate)
switches, we focus on the control of directional movement, both at the molecular
scale and at larger magnitudes. We identify some key challenges remaining in the
field.
PMID- 28426053
TI - Improved spatial resolution for spot sampling in thermal desorption atomic force
microscopy - mass spectrometry via rapid heating functions.
AB - The key to advancing materials is to understand and control their structure and
chemistry. However, thorough chemical characterization is challenging since
existing techniques characterize only a few properties of the specimen, thereby
necessitating multiple measurement platforms to acquire the necessary
information. The multimodal combination of atomic force microscopy (AFM) and mass
spectrometry (MS) transcends existing analytical capabilities for nanometer scale
spatially resolved correlation of the chemical and physical properties of a
sample surface. One such hybrid system employs heated AFM cantilevers for thermal
desorption (TD) sampling of molecules from a surface and subsequent gas phase
ionization and detection of the liberated species by MS. Herein, we report on the
use of voltage pulse trains to tailor cantilever heating such that spot sampling
size was reduced and mass spectral signal was improved compared to constant
voltage, static heating of the cantilever. Desorption efficiency (DE), defined as
the quotient of the mass spectral signal intensity and the volume of the
desorption crater, was used to judge the effectiveness of a particular tailored
heating function. To guide the development and optimization of the heating
functions and aid in interpreting experimental results, a 1D finite element model
was developed that predicted the cantilever response to different heating
functions. Three tailored heating functions that used different combinations,
magnitudes, and durations of rectangular voltage pulses, were used for surface
spot sampling. The resultant sampling spot size and DE were compared to the same
metrics obtained with the conventional method that uses a single voltage pulse.
Using a model system composed of a thin film of ink containing pigment yellow 74
as a model system, desorption craters shrunk from 2 MUm, using the conventional
approach, to 310 nm using the optimum tailored heating function. This same pulsed
heating function produced a 381* improvement in the DE and an 8* improvement in
spatial resolution compared to the conventional heating approach showing that
signal/amount of material sampled was improved significantly by this new
cantilever heating strategy.
PMID- 28426054
TI - Syntheses, structures, and chiroptical and magnetic properties of chiral clusters
built from Schiff bases: a novel [MnIIMnNa] core.
AB - Chiral clusters with MnIIMnNaI and the new MnIIMnNa cores have been synthesised
employing enantiomerically pure Schiff bases and halide ligands. The new
compounds have been characterized by electronic circular dichroism (ECD) and
magnetic susceptibility.
PMID- 28426055
TI - Droplet manipulation on a structured shape memory polymer surface.
AB - While methods for dynamic tuning of surface wettability to manipulate water
droplets have been widely explored for many applications including digital
microfluidics, those based on dynamically changeable surface morphology have
remained challenging to achieve. In this work, we present a structured shape
memory polymer (SMP) surface which shows dynamically tunable surface wettability
through changeable surface morphology in order to manipulate water droplets. The
structured SMP surface involves a SMP pillar array consisting of nanotextured
small and large pillars which can change its morphology between permanent and
temporary shapes upon thermomechanical loading. Specifically, the structured SMP
surface dynamically creates a surface morphological gradient and changes its
surface wettability during thermally induced shape recovery of the SMP pillar
array. Different wetting characteristics of the structured SMP surface between
permanent and temporary shapes are theoretically predicted and experimentally
verified. Based on these measured wetting characteristics, the structured SMP
surface is designed to demonstrate that the morphological difference between two
shapes under a water droplet overcomes contact angle hysteresis, resulting in
driving a water droplet, when combined with the thermal Marangoni effect.
PMID- 28426056
TI - Chemical pathways for poly-anionic isomerisation in the metastable anions of
tetra-deprotonated naphthalene: an intra-molecular inter-ring proton-transfer.
AB - A surprising chemical pathway involving an intra-molecular proton-transfer
between the two different aromatic rings of naphthalene is revealed while
exploring the isomerisation in the metastable tetra-anionic species of tetra
deprotonated naphthalene. The pathways are explored through quantum-mechanical
computations employing a global reaction route mapping (GRRM) strategy. Notably,
several other pathways traced exhibit interesting aspects of poly-anionic
isomerisation in the multiply-charged metastable molecular anions, which can
provide valuable insights into the mechanisms of ring closure and expansion
leading to species like azulenes, cyclodecapentaene, and phenylvinylacetylene.
The metastable poly-anionic species along the pathways were also analysed using a
nuclear charge stabilisation procedure while employing conventional density
functional theory (DFT) with the B3LYP exchange-correlation functional as well as
long-range and dispersion corrected DFT/omegaB97XD and DFT-D3 methods.
Interestingly, the charge stabilisation method using the DFT/B3LYP was found to
be more reliable than the dispersion corrected methods.
PMID- 28426057
TI - In situ synthesis of fluorescent magnetosomes using an organic membrane as a soft
template.
AB - A novel approach was presented for the in situ synthesis of fluorescent
magnetosomes by biological mineralization and carbonization processes for the
first time. The surface structures, magnetism and fluorescence were studied, and
the cytotoxicity tests and fluorescent trace in liposomes were probed. The
fluorescent magnetosomes exhibit not only unique fluorescence and ferromagnetic
properties but also low toxicity and superior imaging capability.
PMID- 28426058
TI - Radical cations of phenyl silatrane.
AB - Electrochemical oxidation of phenylsilatrane (1) in CH3CN/0.1 M Bu4NPF6 has been
studied by voltammetry, UV-Vis and EPR-coupled spectroelectrochemistry supported
by DFT calculations. One-electron withdrawal from the HOMO of 1, formed with a
predominant contribution of the atrane N atom to the 3c-4e system, results in a
short lived radical cation, in which the atrane nitrogen atom is almost planar
and carries most of the spin density showing strong coupling with the protons of
the axially directed C-H bonds of the three adjacent alpha-methylene groups (g =
2.0037, aalphaHax = 37.93 G, aalphaHlat = 0.23 G and abetaH = 1.8 G). EPR
spectroscopy and DFT calculations attest that the unpaired electron in the
radical cation does not reside at the Si atom.
PMID- 28426059
TI - Evolution of dealloying induced strain in nanoporous gold crystals.
AB - We studied the evolution of dealloying-induced strain along the {111} in a Ag-Au
nano-crystal in situ, during formation of nanoporous gold at the initial stage of
dealloying using Bragg coherent X-ray diffractive imaging. The strain magnitude
with maximum probability in the crystal doubled in 10 s of dealloying. Although
formation of nano-pores just began at the surface, the greatest strain is located
60-80 nm deep within the crystal. Dealloying induced a compressive strain in this
region, indicating volume shrinkage occurred during pore formation. The crystal
interior showed a small tensile strain, which can be explained by tensile
stresses induced by the non-dealloyed region upon the dealloyed region during
volume reduction. A surface strain relaxation developed, attributed to atomic
rearrangement during dealloying. This clearer understanding of the role of strain
in the initial stages of formation of nanoporous gold by dealloying can be
exploited for development of new sensors, battery electrodes, and materials for
catalysis.
PMID- 28426060
TI - Hierarchically scaffolded CoP/CoP2 nanoparticles: controllable synthesis and
their application as a well-matched bifunctional electrocatalyst for overall
water splitting.
AB - Transition metal phosphide (TMP) nanostructures have stimulated increasing
interest for use in water splitting owing to their abundant natural sources and
high activity for the hydrogen evolution reaction (HER) and oxygen evolution
reaction (OER). Typically, the preparation of hierarchical TMPs involves the
utilization of expensive or dangerous phosphorus sources, and, in particular, the
understanding of topotactic transformations of the precursors to crystalline
phases-which could be utilized to enhance electrocatalytic performance-remains
very limited. We, herein, report a controllable preparation of CoP/CoP2
nanoparticles well dispersed in flower-like Al2O3 scaffolds (f-CoP/CoP2/Al2O3) as
a bifunctional electrocatalyst for the HER and OER via the phosphorization of a
flower-like CoAl layered double hydroxide precursor. Characterization by in situ
X-ray diffraction (XRD) monitored the topotactic transformation underlying the
controllable formation of CoP/CoP2via tuning the phosphorization time.
Electrocatalytic tests showed that an f-CoP/CoP2/Al2O3 electrode exhibited a
lower onset potential and higher electrocatalytic activity for the HER and OER in
the same alkaline electrolyte than electrodes of flower-like and powdered
CoP/Al2O3. The enhanced electrochemical performance was experimentally supported
by measuring the electrochemically active surface area. The f-CoP/CoP2/Al2O3
composite further generated a current density of 10 mA cm-2 at 1.65 V when used
as a bifunctional catalyst for overall water splitting. Our results demonstrate
that the preparation route based on the LDH precursor may provide an alternative
for investigating diverse TMPs as bifunctional electrocatalysts for water
splitting.
PMID- 28426061
TI - Self-assembly and anion sensing of metal-organic [M6L2] cages from fluorescent
triphenylamine tri-pyrazoles with dipalladium(ii,ii) corners.
AB - Three hexametal-organic cages [(N^N)6Pd6L2]6+ with syn, syn, syn conformation
were synthesized via the coordination of tris(4-(1H-pyrazol-3-yl)phenyl)amine
ligands and [(N^N)2Pd2(NO3)2](NO3)2 dimetallic corners (N^N = 2,2'-bipyridine for
1; 4,4'-dimethylbipyridine for 2; 1,10-phenanthroline for 3). These hexametal
organic cages exhibit anion sensing toward HSO3- in aqueous solution via
fluorescent titration and NMR spectroscopy studies.
PMID- 28426062
TI - A sandwich-shaped M3L2 zinc(ii) complex containing 1,3,5-tris(dimethyl(pyridin-3
yl)silyl)benzene: selective photoluminescence recognition of diiodomethane.
AB - Self-assembly of Zn(ClO4)2 with 1,3,5-tris(dimethyl(pyridin-3-yl)silyl)benzene
(L) as a new C3-symmetric tridentate N-donor gives rise to a discrete sandwich
shaped M3L2 architecture, [Zn3(MU-OH)3L2](ClO4)3.4CH3CN.2H2O. Its blue
photoluminescence is significantly quenched only by CH2I2 among the various small
molecules, CH2Cl2, CH2Br2, CHCl3, 1,2-dichloroethane, EtOH, CH3CN, benzene,
toluene, and phenol.
PMID- 28426063
TI - Hydrophilic 2,9-bis-triazolyl-1,10-phenanthroline ligands enable selective
Am(iii) separation: a step further towards sustainable nuclear energy.
AB - The first hydrophilic, 1,10-phenanthroline derived ligands consisting of only C,
H, O and N atoms for the selective extraction of Am(iii) from spent nuclear fuel
are reported herein. One of these 2,9-bis-triazolyl-1,10-phenanthroline
(BTrzPhen) ligands combined with a non-selective extracting agent, was found to
exhibit process-suitable selectivity for Am(iii) over Eu(iii) and Cm(iii),
providing a clear step forward.
PMID- 28426064
TI - Dual stimuli-triggered dielectric switching and sensing in a host-guest
cyanometallate framework.
AB - The host-guest hybrid cyanometallate framework (MA)(H2O)[Sr(H2O)2Co(CN)6] (1; MA
= methylammonium) shows thermally and chemically triggered dielectric switching
and sensing via a temperature-driven phase transition and a water-driven
reversible structure transformation between 1 and its dehydrated form
(MA)[SrCo(CN)6].
PMID- 28426065
TI - Correction: Elastic strain effects on catalysis of a PdCuSi metallic glass thin
film.
AB - Correction for 'Elastic strain effects on catalysis of a PdCuSi metallic glass
thin film' by Yiyi Yang et al., Phys. Chem. Chem. Phys., 2015, 17, 1746-1754.
PMID- 28426066
TI - Correction: Metal- and additive-free oxygen-atom transfer reaction: an efficient
and chemoselective oxidation of sulfides to sulfoxides with cyclic diacyl
peroxides.
AB - Correction for 'Metal- and additive-free oxygen-atom transfer reaction: an
efficient and chemoselective oxidation of sulfides to sulfoxides with cyclic
diacyl peroxides' by Shaoyan Gan et al., Org. Biomol. Chem., 2017, 15, 2647-2654.
PMID- 28426067
TI - Bioinspired peptosomes with programmed stimuli-responses for sequential drug
release and high-performance anticancer therapy.
AB - Combination therapy with enhanced therapeutic and antimetastatic efficacy has
become promising for cancer treatment. There is an urgent need to design a co
delivery system to sequentially release the drug pair at desired locations that
can increase the intra-tumoral drug concentration and reduce the side effects.
Inspired by virus architecture and function, herein, we developed a peptosome
(PS)-based co-delivery system, PePm/PS/Curcumin (Cur), for the sequential release
of the therapeutic peptide Pe and chemodrug Cur. PS was formed by the self
assembly of amphiphilic alpha-lactalbumin peptides obtained from enzymatic
partial hydrolysis. Then, PS was self-cross-linked with disulfide bonds utilizing
their endogenous thiol groups. The system is responsive to multiple tumor
microenvironments and releases the drugs at specific tumor locations. First,
after PS accumulation in tumor tissue via the EPR effect, the linkage peptide Pm
in PS can be cleaved by matrix metalloproteinases (MMP) enzymatic hydrolysis. Pe
can stay on the cell surface and antagonize the ErbB-2 receptor expression on the
tumor cells. Moreover, the positively charged nature of remaining Mal-PS/Cur
facilitates tumor cell internalization and induces a subsequent proton-sponge
effect for lysosomal escape. Finally, Cur is released in the cytoplasm via a
reduction-induced PS disassembly due to the high level of intracellular GSH. Both
the in vitro and in vivo results exhibited an enhanced antitumor and
antimetastatic efficacy of this system.
PMID- 28426068
TI - Amplification of the molecular chiroptical effect by low-loss dielectric
nanoantennas.
AB - We report here the chiroptical amplification effect occurring in the hybrid
systems consisting of chiral molecules and Si nanostructures. Under resonant
excitation of circularly polarized light, the hybrid systems show strong CD
induction signals at the optical frequency, which arise from both the electric
and magnetic responses of the Si nanostructures. More interestingly, the induced
CD signals from Si-based dielectric nanoantennas are always larger than that from
Au-based plasmonic counterparts. The related physical origin was disclosed.
Furthermore, compared to the Au-based high-loss plasmonic nanoantennas, Si-based
low-loss structures would generate negligible photothermal effect, which makes Si
nanoantennas an optimized candidate to amplify molecular CD signals with ultralow
thermal damage. Our findings may provide a guideline for the design of novel
chiral nanosensors, which are applicable in the fields of biomedicine and
pharmaceutics.
PMID- 28426069
TI - Gradual modification of ITO particle's crystal structure and optical properties
by pulsed UV laser irradiation in a free liquid jet.
AB - Indium tin oxide (ITO) particle coatings are known for high transparency in the
visible, good conductive properties and near-infrared absorption. These
properties depend on ITO particle's stoichiometric composition, defects and size.
Here we present a method to gradually change ITO particle's optical properties by
a simple and controlled laser irradiation process. The defined irradiation
process and controlled energy dose input allows one to engineer the absorption
and transmission of coatings made from these particles. We investigate the role
of the surrounding solvent, influence of laser fluence and the specific energy
dose targeting modification of the ITO particle's morphology and chemistry by
stepwise laser irradiation in a free liquid jet. TEM, SEM, EDX, XPS, XRD and
Raman are used to elucidate the structural, morphological and chemical changes of
the laser-induced ITO particles. On the basis of these results the observed
modification of the optical properties is tentatively attributed to chemical
changes, e.g. laser-induced defects or partial reduction.
PMID- 28426070
TI - Controllable synthesis of ferromagnetic-antiferromagnetic core-shell NWs with
tunable magnetic properties.
AB - Several nanotechnology applications are based on the promising scheme of highly
anisotropic magnetic nanomaterials. Using this idea, we investigated the
structure, magnetic properties, and interfacial exchange anisotropy effects of
the Ni/Cr2O3 and Fe/Cr2O3 core-shell nanowires (NWs) geometry. A template-based
strategy was developed to synthesize Ni (Fe)-Cr2O3 core-shell NWs, which combines
a wet-chemical route and electrodeposition within the nanopores of the membranes.
Structural determination in correlation with magnetic testing shows that the
crystalline Cr2O3-nanoshells (NSs) cause an enhanced exchange bias, providing an
extra source of anisotropy that leads to their magnetic stability. This core
shell NWs geometry, with enhanced anisotropy, should, therefore, motivate further
study related to the applicability of anisotropic nanostructures. Our design
opens a new pathway to obtain optimized heterostructured nanomaterials exhibiting
tunable magnetic properties.
PMID- 28426071
TI - Ca- and Sr-tetrafluoroisophthalates: mechanochemical synthesis, characterization,
and ab initio structure determination.
AB - New fluorinated coordination polymers were prepared mechanochemically by milling
the alkaline earth metal hydroxides MII(OH)2.xH2O (MII: Ca, Sr) with
tetrafluoroisophthalic acid (H2mBDC-F4). The structures of [{Ca(mBDC
F4)(H2O)2}.H2O] (1) and [{Sr(mBDC-F4)(H2O)2}.H2O] (2) were determined based on ab
initio calculations and their powder X-ray diffraction (PXRD) data. The compounds
are isomorphous and crystallize in the orthorhombic space group P212121. The
determined structures were validated by using extended X-ray absorption (EXAFS)
data. The new materials were thoroughly characterized using elemental analysis,
thermal analysis, magic angle spinning NMR, and attenuated total reflection
infrared spectroscopy. Further characterization methods such as BET, dynamic
vapor sorption, and scanning electron microscopy imaging were also used. Our
investigations indicate that mechanochemistry is an efficient method for
preparing such materials.
PMID- 28426072
TI - In situ hybridization of CoOX nanoparticles on N-doped graphene through one step
mineralization of co-responsive hydrogels.
AB - The in situ hydrothermal mineralization for a mixture of graphene oxide (GO) and
Co-responsive supramolecular hydrogels led to a hybrid graphene aerogel, doped
with Co and N elements. The as-prepared aerogels exhibited a competitive half
wave potential (0.840 V, versus RHE) and peak current density (2.35 mA cm-2) to
that of Pt/C (0.836 V, 2.23 mA cm-2, respectively). Furthermore, they
demonstrated a significantly perfect catalytic efficiency (nearly 100% of 4e-
ORR) toward the oxygen reduction reaction (ORR). Insight into the structural
details of the hybrid aerogels indicates that the CoOX active sites anchored on
the graphene matrix play a central role in the upgrading of the catalytic
performance of graphene aerogels.
PMID- 28426073
TI - Ameliorative effects of pepsin-digested chicken liver hydrolysates on development
of alcoholic fatty livers in mice.
AB - With developments in economics and increasing work loads, alcohol abuse becomes
more and more severe, leading to occurrences of alcoholic liver disease (ALD).
Pepsin-digested chicken liver hydrolysates (CLHs) contain high amounts of
glutamic acid, leucine, lysine, and alanine while the contents of taurine,
anserine, and carnosine are also elevated after pepsin hydrolyzation. The
objectives of this study were to evaluate the protective effects of CLHs against
chronic alcohol consumption. The results indicated that the enlarged (p < 0.05)
sizes of liver and spleen, and serum AST, ALT, and ALKP levels of mice fed with
an alcoholic diet were ameliorated by supplementing with CLHs. Moreover,
increased hepatic immunocyte infiltration shown on the H&E staining and higher (p
< 0.05) hepatic triglyceride contents, TBARS values, and proinflammatory cytokine
levels in alcoholic diet fed mice were also reduced (p < 0.05) by supplementing
with CLHs. Those benefits were attributed to up-regulated fatty acid beta
oxidation and down-regulated fatty acid synthesis, as well as increased (p <
0.05) SOD, CAT, and GPx activities, TEAC levels, and elevated alcohol metabolic
enzymatic activities (ALDH).
PMID- 28426074
TI - Probing the local structure of Prussian blue electrodes by 113Cd NMR
spectroscopy.
AB - We demonstrate that 113Cd NMR is a potent technique to monitor the local
electronic and structural states of the Prussian blue electrode during Li+
intercalation, providing an atomic-scale insight into the reaction mechanism.
PMID- 28426075
TI - Functionalized vinylsilanes via highly efficient and recyclable Pt-nanoparticle
catalysed hydrosilylation of alkynes.
AB - A mild, selective and facile synthesis of vinylsilanes via a recyclable platinum
nanoparticle catalysed hydrosilylation of alkynes is reported. Various
functionalized alkynes are selectively hydrosilylated to furnish functional beta
E vinylsilanes in high yields. The catalytic effectiveness, ease of catalyst
recovery and recyclability of the polysiloxane stabilized Pt-nanoparticle
catalyst are the major achievements of this work. Detailed in situ
characterization using Electron Microscopy and controlled poisoning experiments
supports the participation of Pt-nanoparticles as active catalysts.
PMID- 28426076
TI - An amidato divalent ytterbium cluster: synthesis and molecular structure, its
reactivity to carbodiimides and application in the guanylation reaction.
AB - A divalent ytterbium amidate 1 ([Yb3L6].2C7H8 for short) was synthesized via
amine-elimination of Yb[N(SiMe3)2]2(TMEDA) with an amide proligand N-2,6
diisopropylphenylbenzamide HL (L = 2,6-iPr2C6H3NC(O)Ph) and structurally
characterized to be a trinuclear symmetric cluster. Further studies on the
reduction of iPrN[double bond, length as m-dash]C[double bond, length as m
dash]NiPr by complex 1 provide Yb(iii) complex 2 in hexane-THF ([(YbL2)2(MU
NiPrCNiPr)][YbL3(THF)].C7H8), which is composed of two subunits in a unit cell,
one is a bridged Yb(iii) carbene, just the same as complex 4 ([(YbL2)2(MU
NiPrCNiPr)].3C7H8) obtained in the same reaction in toluene, and the other is a
homoleptic monomeric Yb(iii) amidate (YbL3). It is also found that complex 2
decomposed to complex 3 ([YbL3]2.2C7H8) and 4 at 90 degrees C in toluene.
Complexes 1-4 were confirmed by X-ray structure determination. Furthermore,
complex 4 was proved to be a more active species than its precursor 1 in the
catalytic addition of amines to carbodiimides. Finally, complex 1 was found to be
an excellent pre-catalyst for the guanylation reaction with a wide scope of
substrates.
PMID- 28426077
TI - Robust raspberry-like metallo-dielectric nanoclusters of critical sizes as SERS
substrates.
AB - Raspberry-like nano-objects made of large plasmonic satellites (>10 nm) covering
a central dielectric particle have many potential applications as photonic
materials, superlenses and (bio-) sensors, but their synthesis remains
challenging. Herein, we show how to build stable and robust raspberry-like nano
systems with close-packed satellites, by combining monodisperse silica particles
(80 or 100 nm diameter) and oppositely charged noble metal nanoparticles (Au or
Ag) with well-defined sizes (10-50 nm). The spectral characteristics of their
associated plasmonic resonances (wavelength, linewidth, extinction cross-section)
and the electromagnetic coupling between satellites were observed using the
spatial modulation spectroscopy technique and interpreted through a numerical
model. The composite nano-objects exhibit numerous hot spots at satellite
junctions, resulting in excellent surface-enhanced Raman scattering (SERS)
performance. The SERS efficiency of the raspberry-like clusters is highly
dependent on their structure.
PMID- 28426078
TI - An intravascular bioartificial pancreas device (iBAP) with silicon nanopore
membranes (SNM) for islet encapsulation under convective mass transport.
AB - Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet
viability and functionality due to inadequate mass transfer resulting in islet
hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration
based BAP devices possess enhanced glucose-insulin kinetics, the polymer
membranes used in these devices provide inadequate ultrafiltrate flow rates and
result in excessive thrombosis. Here, we report the silicon nanopore membrane
(SNM), which exhibits a greater hydraulic permeability and a superior pore size
selectivity compared to polymer membranes for use in BAP applications.
Specifically, we demonstrate that the SNM-based intravascular BAP with ~10 and
~40 nm pore sized membranes support high islet viability (>60%) and functionality
(<15 minute insulin response to glucose stimulation) at clinically relevant islet
densities (5700 and 11 400 IE per cm2) under convection in vitro. In vivo studies
with ~10 nm pore sized SNM in a porcine model showed high islet viability (>85%)
at clinically relevant islet density (5700 IE per cm2), c-peptide concentration
of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection.
These promising findings offer insights on the development of next generation of
full-scale intravascular devices to treat T1D patients in the future.
PMID- 28426079
TI - Oxidation suppression during hydrothermal phase reversion allows synthesis of
monolayer semiconducting MoS2 in stable aqueous suspension.
AB - This letter demonstrates a simple method to achieve high-yields of 1H
semiconducting MoS2 monolayers in concentrated, colloidally-stable aqueous
suspension. The method is based on oxidation suppression during the hydrothermal
processing step used for metal-to-semiconductor phase reversion. Accompanying DFT
calculations on elementary steps in the MoS2 wet oxidation reaction suggest that
a two-site corrosion mechanism is responsible for the observed high reactivity
and low stability of 1T metallic MoS2.
PMID- 28426080
TI - C-reactive protein and interleukin 6 microfluidic immunoassays with on-chip pre
stored reagents and centrifugo-pneumatic liquid control.
AB - We present a fully automated centrifugal microfluidic method for particle based
protein immunoassays. Stick-pack technology is employed for pre-storage and
release of liquid reagents. Quantitative layout of centrifugo-pneumatic particle
handling, including timed valving, switching and pumping is assisted by network
simulations. The automation is exclusively controlled by the spinning frequency
and does not require any additional means. New centrifugal microfluidic process
chains are developed in order to sequentially supply wash buffer based on
frequency dependent stick-pack opening and pneumatic pumping to perform two
washing steps from one stored wash buffer; pre-store and re-suspend
functionalized microparticles on a disk; and switch between the path of the waste
fluid and the path of the substrate reaction product with 100% efficiency. The
automated immunoassay concept is composed of on demand ligand binding, two
washing steps, the substrate reaction, timed separation of the reaction products,
and termination of the substrate reaction. We demonstrated separation of
particles from three different liquids with particle loss below 4% and residual
liquid remaining within particles below 3%. The automated immunoassay concept was
demonstrated by means of detecting C-reactive protein (CRP) in the range of 1-81
ng ml-1 and interleukin 6 (IL-6) in the range of 64-13 500 pg ml-1. The limit of
detection and quantification were 1.0 ng ml-1 and 2.1 ng ml-1 for CRP and 64 pg
ml-1 and 205 pg ml-1 for IL-6, respectively.
PMID- 28426081
TI - Total substitution of dietary fish oil by vegetable oils stimulates muscle
hypertrophic growth in Senegalese sole and the upregulation of fgf6.
AB - The long term effects of fish oil (FO) substitution by increasing the levels of
vegetable oils (VO), 0% (CTR), 50% (VO50) and 100% (VO100), in diets for
Senegalese sole were evaluated in terms of skeletal muscle cellularity and
expression of related genes. After 140 days of feeding, all fish had similar body
weight and length. The inclusion of 50% VO did not result in differences in
muscle cellularity, but dorsal muscle cross-sectional area and fast-twitch fibre
diameter increased in fish fed total FO substitution, whilst fibre density was
reduced (P < 0.05) in relation to CTR. The total number of fibres was similar in
all treatments. FO substitution did not affect the transcript levels of myogenic
genes (myf5, mrf4, myog, myod1, myod2), but resulted in a two-fold increase of
fgf6 transcript levels compared to CTR (P < 0.05). The relative expression of igf
I was higher in VO100 than in VO50, but was similar to CTR. FO substitution
resulted in cellularity changes related to the stimulation of muscle hypertrophic
growth, but not hyperplastic growth, and associated with a nutritional modulation
of fgf6 by dietary VO. This study indicates that 50% VO does not affect the
muscle phenotype, but total FO substitution stimulates muscle hypertrophy.
PMID- 28426082
TI - Deciphering of interactions between platinated DNA and HMGB1 by
hydrogen/deuterium exchange mass spectrometry.
AB - A high mobility group box 1 (HMGB1) protein has been reported to recognize both
1,2-intrastrand crosslinked DNA by cisplatin (1,2-cis-Pt-DNA) and monofunctional
platinated DNA using trans-[PtCl2(NH3)(thiazole)] (1-trans-PtTz-DNA). However,
the molecular basis of recognition between the trans-PtTz-DNA and HMGB1 remains
unclear. In the present work, we described a hydrogen/deuterium exchange mass
spectrometry (HDX-MS) method in combination with docking simulation to decipher
the interactions of platinated DNA with domain A of HMGB1. The global deuterium
uptake results indicated that 1-trans-PtTz-DNA bound to HMGB1a slightly tighter
than the 1,2-cis-Pt-DNA. The local deuterium uptake at the peptide level revealed
that the helices I and II, and loop 1 of HMGB1a were involved in the interactions
with both platinated DNA adducts. However, docking simulation disclosed different
H-bonding networks and distinct DNA-backbone orientations in the two Pt-DNA
HMGB1a complexes. Moreover, the Phe37 residue of HMGB1a was shown to play a key
role in the recognition between HMGB1a and the platinated DNAs. In the cis-Pt-DNA
HMGB1a complex, the phenyl ring of Phe37 intercalates into a hydrophobic notch
created by the two platinated guanines, while in the trans-PtTz-DNA-HMGB1a
complex the phenyl ring appears to intercalate into a hydrophobic crevice formed
by the platinated guanine and the opposite adenine in the complementary strand,
forming a penta-layer pi-pi stacking associated with the adjacent thymine and the
thiazole ligand. This work demonstrates that HDX-MS associated with docking
simulation is a powerful tool to elucidate the interactions between platinated
DNAs and proteins.
PMID- 28426083
TI - Energetic isomers of 1,2,4,5-tetrazine-bis-1,2,4-triazoles with low toxicity.
AB - A series of nitrogen-rich "green" Energetic Materials (EMs), some with improved
sensitivity, thermostability, and very low toxicity, were synthesized on the
basis of 3,5-diamino-1,2,4-triazole (DAT) and 1,2,4,5-tetrazine building blocks.
Since DAT contains several nucleophilic reactive sites, obtaining selective
reactivity and specific isomeric products with 1,2,4,5-tetrazine precursors is a
challenging task. We developed reaction conditions under which specific isomers
could be prepared. On evaluating these compounds for their energetic properties,
we found that N5,N5'-(1,2,4,5-tetrazine-3,6-diyl)-bis(1H-1,2,4-triazole-3,5
diamine) 1 has very high thermostability (onset of decomposition temperature at
357 degrees C) and it is insensitive to impact (Im > 98 J), friction (>360 N)
and electrostatic discharge (2512 mJ). A detonation velocity (Vod) of 8180 m s-1
was calculated for compound 1 and it was found to have extremely low toxicity in
human cells (normal dermal fibroblasts) and in environmental bacteria (Vibrio
fischeri). In combination with oxidants, compound 1 can generate 1225 L of gases
(per kg of energetic mixture of an oxidant and compound 1), which makes this
material a prospective component in solid propellants and a very good candidate
for the development of solid state gas generators for clean fire-extinguishing
systems and for a broad range of other civil and defense applications that
require the use of "green" and insensitive EMs.
PMID- 28426084
TI - Synthesis of 2-amino- and 2-arylazoazulenes via nucleophilic aromatic
substitution of 2-chloroazulenes with amines and arylhydrazines.
AB - The SNAr reaction of 2-chloroazulene derivative 1 with ethoxycarbonyl groups at
the 1,3-positions of the azulene ring with several amines afforded the
corresponding 2-aminoazulenes 3-9 in excellent yields. 2-Chloroazulene (2)
without the electron-withdrawing groups reacted with highly nucleophilic cyclic
amines (i.e., morpholine, piperidine and pyrrolidine) under the high-temperature
conditions in a sealed tube to produce the corresponding 2-aminoazulenes 10-12 in
good yields. 2-Aminoazulenes 10-14 without the electron-withdrawing groups were
also obtained in good yields by the treatment of compounds 3-7 with 100% H3PO4,
but in the cases of the reaction of 8 and 9 with a secondary amine function, the
decomposition of the products resulted. The synthesis of 2-arylazoazulenes 15-18
was also established via the SNAr reaction of 1 with arylhydrazines. The optical
and electrochemical properties of the 2-arylazoazulene derivatives were examined
by UV/Vis spectroscopy, theoretical calculations and voltammetric experiments.
PMID- 28426085
TI - N-Heterocyclic carbene-catalyzed stereoselective construction of olefinic carbon
sulfur bonds via cross-coupling reaction of gem-difluoroalkenes and thiols.
AB - A novel organocatalytic olefinic carbon-sulfur bond forming reaction was
developed. Under the catalysis of 10 mol% stable N-heterocyclic carbene, thiols
undergo direct nucleophilic substitution reaction with gem-difluoroalkenes to
produce alpha-fluorovinyl thioethers in high yields with excellent Z-selectivity.
In this process, bases are not necessary.
PMID- 28426086
TI - Circularly polarised luminescence of pyrenyl di- and tri-peptides with mixed d-
and l-amino acid residues.
AB - Multiple pyrenes as pendants of enantioimpure di-/tripeptides (abbreviated as N
LD-C, N-DL-C, N-LLD-C and N-DDL-C) showed pyrene-origin CPL and CD signals, which
were associated with conflicting CPL-/CD-signs, compared to the corresponding
enantiopure di-/tri-peptides.
PMID- 28426087
TI - A pH-controlled recyclable indolinooxazolidine tagged N-heterocyclic carbene Ru
catalyst for olefin metathesis.
AB - An indolinooxazolidine tagged N-heterocyclic carbene Ru olefin metathesis
catalyst was synthesized and the molecular structure of this new Ru complex was
determined by single crystal X-ray diffraction. This complex is a homogeneous
catalyst and can be recovered by controlling the polarity of the
indolinooxazolidine tag. Under acidic conditions the indolinooxazolidine tag
exists as an open protonated form and under basic conditions the tag is in a
closed form. The distribution of this catalyst in a two-phase system can be
controlled by simply changing the pH, making the recovery of this catalyst easily
obtainable.
PMID- 28426088
TI - Nanoscale imaging and spectroscopy of band gap and defects in polycrystalline
photovoltaic devices.
AB - Improving the power conversion efficiency of photovoltaic (PV) devices is
challenging because the generation, separation and collection of electron-hole
pairs are strongly dependent on details of the nanoscale chemical composition and
defects which are often poorly known. In this work, two novel scanning probe nano
spectroscopy techniques, direct-transmission near-field scanning optical
microscopy (dt-NSOM) and photothermal induced resonance (PTIR), are implemented
to probe the distribution of defects and the bandgap variation in thin lamellae
extracted from polycrystalline CdTe PV devices. dt-NSOM provides high-contrast
spatially-resolved maps of light transmitted through the sample at selected
wavelengths. PTIR provides absorption maps and spectra over a broad spectral
range, from visible to mid-infrared. Results show variation of the bandgap
through the CdTe thickness and from grain to grain that is spatially uncorrelated
with the distributions of shallow and deep defects.
PMID- 28426089
TI - Ferrogels based on entrapped metallic iron nanoparticles in a polyacrylamide
network: extended Derjaguin-Landau-Verwey-Overbeek consideration, interfacial
interactions and magnetodeformation.
AB - A new kind of ferrogel with entrapped metallic iron nanoparticles causing unusual
magnetodeformation is presented. Crosslinked polyacrylamide (PAAm) based
ferrogels embedded with iron nanoparticles (MNPs) were synthesized by free
radical polymerization in aqueous medium. Spherical iron MNPs with average
diameter 66 nm were synthesized by the electrical explosion of wire and modified
by interfacial adsorption of linear polyacrylamide (LPAAm). Extended Derjaguin
Landau-Verwey-Overbeek (xDLVO) calculations based on the superposing of van der
Waals, electrostatic, steric, and magnetic contributions showed that polymeric
encapsulation of nanoparticles by LPAAm is one of the most suitable pathways for
preparing stable aqueous dispersions of iron nanoparticles. Microcalorimetry
confirmed the presence of strong interfacial adhesion forces between LPAAm chains
and the surface of iron nanoparticles. By keeping the same crosslinking density
of a polymer network (i.e. 100 : 1, monomer to crosslinker ratio) and varying the
initial monomer concentration, an influence of the extent of polymer network
reticulation on the mechanical properties and subsequently, magneto-elastic
properties was demonstrated. It was found that the upper limit of the shear
modulus for the synthesis of a new kind of polyacrylamide based ferrogel to
exhibit any usable magnetodeformation under the application of a uniform external
magnetic field of 420 mT is ca. 1 kPa. Magnetodeformation of cylindrical ferrogel
samples was observed in the form of an overall volume contraction accompanied by
a homogeneous decrease in all dimensions. The deformation was found to be maximum
(around 10%) for the aspect ratio of 1/1 and it was lower and similar for the
samples with 1/2 and 2/1 aspect ratios. Such a type of magnetic response is
significantly different from the behavior observed in the existing reports on
ferroelastomers.
PMID- 28426090
TI - Oleuropein down-regulated IL-1beta-induced inflammation and oxidative stress in
human synovial fibroblast cell line SW982.
AB - Rheumatoid arthritis (RA) is a chronic and systemic inflammatory autoimmune
disease mainly characterized by aggressive hyperproliferation of synovial
fibroblasts (SFs). It is accompained by a massive infiltration of inflammatory
immune cells inducing progressive matrix degradation, destruction of cartilage
and bone erosion through the production of inflammatory mediators. Oleuropein is
the most prevalent phenolic component in olive leaves, seed, pulp and peel of
unripe olives and is responsible for the characteristic bitter taste of
unprocessed olives. This secoiridoid possesses well-documented pharmacological
properties, including antioxidant and anti-inflammatory properties, and is
available as a food supplement in Mediterranean countries. However, to date, anti
arthritic effects of oleuropein on SFs have not been yet elucidated. Thus, the
aim of the present study was to investigate the potential effects of oleuropein,
on IL-1beta-induced production of inflammatory mediators and oxidative stress in
the human synovial sarcoma cell line (SW982). In order to gain a better insight
into mechanisms of action, signaling pathways were also explored. Cell viability
was determined using the sulforhodamine B (SRB) assay. The expression of
inflammatory cytokines IL-6, TNF-alpha, MMP-1 and MMP-3 was evaluated by ELISA.
Moreover, changes in the protein expression of cyclooxygenase (COX)-2, microsomal
prostaglandin E synthase-1 (mPGES-1) as well as mitogen-activated protein kinase
(MAPKs), nuclear factor kappa B (NF-kappaB), and nuclear factor-erythroid 2
related and heme oxygenase-1 (HO-1) signalling pathways were analysed by western
blot. Oleuropein exerted anti-inflammatory and anti-oxidant effects via down
regulation of MAPK and NF-kappaB signaling pathways and induction of Nrf2-linked
HO-1 controlling the production of inflammatory mediators decreasing IL-6 and TNF
alpha cytokines, MMP-1 and MMP-3 levels and mPGES-1 and COX-2 overexpression.
Thus, oleuropein might provide a basis for developing a new dietary strategy for
the prevention and management of RA.
PMID- 28426091
TI - Distinguishing between homogeneous and heterogeneous hydrogen-evolution catalysis
with molecular cobalt complexes.
AB - Molecular proton-reduction catalysts can decompose under the acidic conditions
required for hydrogen evolution, resulting in formation of secondary metal
containing materials. Using an electrochemical quartz crystal microbalance
(EQCM), we report a new method for probing electrodeposition of catalytically
active heterogeneous material from molecular precursors. The data collected
suggest that EQCM can provide a direct measure of the homogeneity of molecular
proton-reduction catalysts over short timescales.
PMID- 28426092
TI - Correction: High precision, localized proton gradients and fluxes generated by a
microelectrode device induce differential growth behaviors of pollen tubes.
AB - Correction for 'High precision, localized proton gradients and fluxes generated
by a microelectrode device induce differential growth behaviors of pollen tubes'
by Chengzhi Hu et al., Lab Chip, 2017, 17, 671-680.
PMID- 28426093
TI - Biophysical properties, thermal stability and functional impact of 8-oxo-7,8
dihydroguanine on oligonucleotides of RNA-a study of duplex, hairpins and the
aptamer for preQ1 as models.
AB - 8-10: A better understanding of the effects that oxidative lesions have on RNA is
of importance to understand their role in the development/progression of disease.
8-oxo-7,8-dihydroguanine was incorporated into RNA to understand its structural
and functional impact on RNA:RNA and RNA:DNA duplexes, hairpins and pseudoknots.
One to three modifications were incorporated into dodecamers of RNA [AAGA GGG
AUGAC] resulting in thermal destabilization (Delta T m - 10 degrees C per
lesion). Hairpins with tetraloops c-UUCG*-g* ( ), a-ACCG-g* ( ), c-UUG*G*-g* ( )
and c-ACG*G*-g* ( ) were modified and used to determine thermal stabilities,
concluding that: (i) modifying the stem leads to destabilization unless adenosine
is the opposing basepair of 8-oxoGua; (ii) modification at the loop is position-
and sequence-dependent and varies from slight stabilization to large
destabilization, in some cases leading to formation of other secondary structures
(hairpin->duplex). Functional effects were established using the aptamer for preQ
1 as model. Modification at G5 disrupted the stem P1 and inhibited recognition of
the target molecule 7-methylamino-7-deazaguanine (preQ 1 ). Modifying G11 results
in increased thermal stability, albeit with a K d 4-fold larger than its
canonical analog. These studies show the capability of 8-oxoG to affect structure
and function of RNA, resulting in distinct outcomes as a function of number and
position of the lesion.
PMID- 28426094
TI - SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription.
AB - SIRT7 is an NAD+-dependent protein deacetylase that regulates cell growth and
proliferation. Previous studies have shown that SIRT7 is required for RNA
polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a
proteomic approach to identify novel molecular targets and characterize the role
of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous
proteins involved in transcriptional regulation and RNA metabolism, the majority
of interactions requiring ongoing transcription. In addition to its role in Pol I
transcription, we found that SIRT7 also regulates transcription of snoRNAs and
mRNAs. Mechanistically, SIRT7 promotes the release of P-TEFb from the inactive
7SK snRNP complex and deacetylates CDK9, a subunit of the elongation factor P
TEFb, which activates transcription by phosphorylating serine 2 within the C
terminal domain (CTD) of Pol II. SIRT7 counteracts GCN5-directed acetylation of
lysine 48 within the catalytic domain of CDK9, deacetylation promoting CTD
phosphorylation and transcription elongation.
PMID- 28426095
TI - Models of global gene expression define major domains of cell type and tissue
identity.
AB - The current classification of cells in an organism is largely based on their
anatomic and developmental origin. Cells types and tissues are traditionally
classified into those that arise from the three embryonic germ layers, the
ectoderm, mesoderm and endoderm, but this model does not take into account the
organization of cell type-specific patterns of gene expression. Here, we present
computational models for cell type and tissue specification derived from a
collection of 921 RNA-sequencing samples from 272 distinct mouse cell types or
tissues. In an unbiased fashion, this analysis accurately predicts the three
known germ layers. Unexpectedly, this analysis also suggests that in total there
are eight major domains of cell type-specification, corresponding to the
neurectoderm, neural crest, surface ectoderm, endoderm, mesoderm, blood mesoderm,
germ cells and the embryonic domain. Further, we identify putative genes
responsible for specifying the domain and the cell type. This model has
implications for understanding trans-lineage differentiation for stem cells,
developmental cell biology and regenerative medicine.
PMID- 28426096
TI - Managing the sequence-specificity of antisense oligonucleotides in drug
discovery.
AB - All drugs perturb the expression of many genes in the cells that are exposed to
them. These gene expression changes can be divided into effects resulting from
engaging the intended target and effects resulting from engaging unintended
targets. For antisense oligonucleotides, developments in bioinformatics
algorithms, and the quality of sequence databases, allow oligonucleotide
sequences to be analyzed computationally, in terms of the predictability of their
interactions with intended and unintended RNA targets. Applying these tools
enables selection of sequence-specific oligonucleotides where no- or only few
unintended RNA targets are expected. To evaluate oligonucleotide sequence
specificity experimentally, we recommend a transcriptomics protocol where two or
more oligonucleotides targeting the same RNA molecule, but with entirely
different sequences, are evaluated together. This helps to clarify which changes
in cellular RNA levels result from downstream processes of engaging the intended
target, and which are likely to be related to engaging unintended targets. As
required for all classes of drugs, the toxic potential of oligonucleotides must
be evaluated in cell- and animal models before clinical testing. Since potential
adverse effects related to unintended targeting are sequence-dependent and
therefore species-specific, in vitro toxicology assays in human cells are
especially relevant in oligonucleotide drug discovery.
PMID- 28426097
TI - Landscape of RNA polyadenylation in E. coli.
AB - Polyadenylation is thought to be involved in the degradation and quality control
of bacterial RNAs but relatively few examples have been investigated. We used a
combination of 5?-tagRACE and RNA-seq to analyze the total RNA content from a
wild-type strain and from a poly(A)polymerase deleted mutant. A total of 178
transcripts were either up- or down-regulated in the mutant when compared to the
wild-type strain. Poly(A)polymerase up-regulates the expression of all genes
related to the FliA regulon and several previously unknown transcripts, including
numerous transporters. Notable down-regulation of genes in the expression of
antigen 43 and components of the type 1 fimbriae was detected. The major
consequence of the absence of poly(A)polymerase was the accumulation of numerous
sRNAs, antisense transcripts, REP sequences and RNA fragments resulting from the
processing of entire transcripts. A new algorithm to analyze the position and
composition of post-transcriptional modifications based on the sequence of
unencoded 3?-ends, was developed to identify polyadenylated molecules. Overall
our results shed new light on the broad spectrum of action of polyadenylation on
gene expression and demonstrate the importance of poly(A) dependent degradation
to remove structured RNA fragments.
PMID- 28426098
TI - Targeting chromatin defects in selected solid tumors based on oncogene addiction,
synthetic lethality and epigenetic antagonism.
AB - Background: Although the role of epigenetic abnormalities has been studied for
several years in cancer genesis and development, epigenetic-targeting drugs have
historically failed to demonstrate efficacy in solid malignancies. However,
successful targeting of chromatin remodeling deficiencies, histone writers and
histone reader alterations has been achieved very recently using biomarker-driven
and mechanism-based approaches. Epigenetic targeting is now one of the most
active areas in drug development and could represent novel therapeutic
opportunity for up to 25% of all solid tumors. Material and methods: We reviewed
preclinical and clinical studies that described epigenetic oncogenic addictions,
synthetic lethal relationships or epigenetic antagonisms in chromatin regulators.
Experimental approaches, their clinical relevance and applicability, as well as
corresponding on-going studies are described. Results: The most successful
approaches that have been clinically validated so far include the targeting of
the BRD4-NUT fusion transcript in NUT-midline carcinoma by BET (Bromodomain Extra
Terminal) inhibitors, and the use of EZH2 (Enhancer of Zest Homolog 2) inhibitors
in SMARCB1-deficient malignant rhabdoid tumors and SMARCA4-deficient ovarian
small cell carcinomas. Clinical validation is still required for other synthetic
lethal relationships or epigenetic antagonisms, including those described between
EZH2 inhibitors and deficiencies in components of the Polycomb or SWI/SNF
chromatin-remodeling complexes (including BAP1, ARID1A and PBRM1 subunits), as
well as between the CREBBP and EP300 histone acetylases. Further, interplays
between epigenetic modifiers and non-epigenetic cellular processes might be
therapeutically exploited, and combinatorial strategies could be envisioned to
overcome resistance or to sensitize cells to already approved drugs. Conclusion:
Epigenetic-targeting drugs have historically failed proving efficacy in solid
malignancies when used broadly, but novel mechanism-based approaches in
molecularly selected patient populations have facilitated recent successes in
proof-of-concept studies in solid tumors. Appropriate clinical trial design and
molecular patient selection will be key for the success of epigenetic modifiers
in solid tumours.
PMID- 28426099
TI - Improving brain penetration of kinase inhibitors in lung cancer patients with
oncogene dependency.
PMID- 28426100
TI - Don't forget the host: a potential role for germinal polymorphisms as markers for
checkpoint inhibitors.
PMID- 28426101
TI - Cancer risk among 21st century blood transfusion recipients.
AB - Background: Some carcinogenic viruses are known to be transmissible by blood
transfusion. Intensive viral screening of transfused blood now exists in most
countries. In the UK, high-sensitivity nucleic acid amplification tests for
hepatitis C virus were introduced in 1999 and it was thought that this would
reduce, and possibly eliminate, transfusion-related liver cancer. We aimed to
investigate cancer risk in recipients of blood transfusion in 2000 or after.
Methods: A total of 1.3 million UK women recruited in 1998 on average were
followed for hospital records of blood transfusion and for cancer registrations.
After excluding women with cancer or precancerous conditions before or at the
time of transfusion, Cox regression yielded adjusted relative risks of 11 site
specific cancers for women with compared to without prior blood transfusion.
Results: During follow up, 11 274 (0.9%) women had a first recorded transfusion
in 2000 or after, and 1648 (14.6%) of them were subsequently diagnosed with
cancer, a mean 6.8 years after the transfusion. In the first 5 years after
transfusion there were significant excesses for most site-specific cancers
examined, presumably because some had preclinical cancer. However, 5 or more
years (mean 8 years) after blood transfusion, there were significant excess risks
only for liver cancer (adjusted relative risk = 2.63, 95%CI 1.45-4.78) and for
non-Hodgkin lymphoma (adjusted relative risk = 1.74, 1.21-2.51). When analyses
were restricted to those undergoing hip or knee replacement surgery, the
commonest procedure associated with transfusion, these relative risks were not
materially altered. Conclusions: In a large cohort of UK women, transfusions in
the 21st century were associated with long-term increased risks of liver cancer
and non-Hodgkin lymphoma. Some of these malignancies may have been caused by
carcinogenic agents that are not currently screened for in transfused blood.
PMID- 28426102
TI - Infection-related complications during treatment for childhood acute
lymphoblastic leukemia.
AB - Background: Comprehensive studies on neutropenia and infection-related
complications in patients with acute lymphoblastic leukemia (ALL) are lacking.
Patients and methods: We evaluated infection-related complications that were
grade >=3 on National Cancer Institute's Common Terminology Criteria for Adverse
Events (version 3.0) and their risk factors in 409 children with newly diagnosed
ALL throughout the treatment period. Results: Of the 2420 infection episodes,
febrile neutropenia and clinically or microbiologically documented infection were
seen in 1107 and 1313 episodes, respectively. Among documented infection
episodes, upper respiratory tract was the most common site (n = 389), followed by
ear (n = 151), bloodstream (n = 147), and gastrointestinal tract (n = 145)
infections. These episodes were more common during intensified therapy phases
such as remission induction and reinduction, but respiratory and ear infections,
presumably viral in origin, also occurred during continuation phases. The 3-year
cumulative incidence of infection-related death was low (1.0+/-0.9%, n = 4),
including 2 from Bacillus cereus bacteremia. There was no fungal infection
related mortality. Age 1-9.9 years at diagnosis was associated with febrile
neutropenia (P = 0.002) during induction and febrile neutropenia and documented
infection (both P < 0.001) during later continuation. White race was associated
with documented infection (P = 0.034) during induction. Compared with low-risk
patients, standard- and high-risk patients received more intensive therapy during
early continuation and had higher incidences of febrile neutropenia (P < 0.001)
and documented infections (P = 0.043). Furthermore, poor neutrophil surge after
dexamethasone pulses during continuation, which can reflect the poor bone marrow
reserve, was associated with infections (P < 0.001). Conclusions: The incidence
of infection-related death was low. However, young age, white race, intensive
chemotherapy, and lack of neutrophil surge after dexamethasone treatment were
associated with infection-related complications. Close monitoring for prompt
administration of antibiotics and modification of chemotherapy should be
considered in these patients.
PMID- 28426103
TI - Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a
single centre experience and review of the literature.
AB - Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly
improved survival for patients with advanced melanoma in recent years. Anti-CTLA
4 and anti-PD1 antibodies have been approved following large Phase III trials.
Immune-related neurological toxicity of varying severity has been reported in the
literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab
and pembrolizumab is reported as <1% in published clinical trials. We aimed to
identify the incidence of neurotoxicity in our institution across anti-CTLA4 and
anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab. We
also review the existing literature and propose an investigation and management
algorithm. Methods: All patients with advanced melanoma treated with ipilimumab,
nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab (ipi +
nivo), managed at the Royal Marsden Hospital between September 2010 and December
2015, including patients on (published) clinical trials were included. Medical
records for each patient were reviewed and information on neurotoxicity recorded.
A systematic search strategy was performed to collate existing reports of
neurological toxicity. Results: In total, 413 immunotherapy treatment episodes in
352 patients were included, with median follow-up of 26.7 months. Ten cases of
neurotoxicity were recorded, affecting 2.8% of patients overall, ranging from
grade 1 to 4, affecting both central and peripheral nervous systems. A rate of
14% was noted with ipi + nivo. Three of five patients commenced on
corticosteroids responded to these. Six patients had made a full recovery at the
time of reporting. A favorable radiological response was found in 7 of the 10
cases. Unusual presentations are described in detail. Conclusions: Neurological
toxicity is not uncommon, and may be more frequent in patients treated with
combination ipi + nivo. Patterns of presentation and response to treatment are
varied. A prompt and considered approach is required to optimize outcomes in this
group of patients.
PMID- 28426104
TI - A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in
patients with previously treated non-small-cell lung cancer.
AB - Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC)
and small-cell lung cancer. However, no direct comparisons between amrubicin and
docetaxel, a standard treatment for NSCLC, have been reported. Patients and
methods: We conducted a randomized phase III trial of Japanese NSCLC patients
after one or two chemotherapy regimens. Patients were randomized to amrubicin (35
mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks).
Outcomes included progression-free survival, overall survival, tumor responses,
and safety. Results: Between October 2010 and June 2012, 202 patients were
enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0
months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were
comparable in the amrubicin and docetaxel groups, respectively. The overall
response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel
groups, respectively (P = 0.45). The disease control rate was 55.7% in both
groups. Adverse events occurred in all patients, and included grade >=3
neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and
docetaxel groups, respectively, grade >=3 leukopenia occurred in 63.3% and 70.7%,
and grade >=3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the
amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in
the amrubicin group, three were considered related to amrubicin and resolved
without treatment discontinuation. Conclusions: This was the first phase III
study to compare amrubicin and docetaxel in patients with pretreated NSCLC.
Amrubicin did not significantly improve the primary endpoint of PFS compared with
docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).
PMID- 28426105
TI - The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in
ductal carcinoma in situ of the breast.
AB - Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct
in invasive breast cancer, but their clinical role in ductal carcinoma in situ
(DCIS) has not been ascertained. Patients and methods: We evaluated the
prevalence and clinical relevance of TILs in a well annotated series of 1488
consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria
for TILs evaluation were pre-defined involving the International Immuno-Oncology
Biomarker Working Group. TILs percentage was considered both as a continuous and
categorical variable. Levels of TILs were examined for their associations with
ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488
patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% >=50% peri
ductal stromal lymphocytes. The interobserver agreement in TILs evaluation,
measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95
0.97). At univariable analysis, clinical factors significantly associated with
TILs (P <=0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2
positive DCIS were more frequently associated with TILs (24% of patients with
TILs >=50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%)
and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association
between TILs as a continuous variable and the risk of IBEs. Likewise, when
patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and
>=50%), no statistically significant association was observed (10-year cumulative
incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion:
TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a
significant association between TILs and the 10-year risk of IBE, our data
suggest that immunotherapies might be considered in subsets of DCIS patients.
PMID- 28426107
TI - Controversies and consensus in the innovation access for cancer therapy in the
European countries: on the subject of metastatic prostate cancer.
AB - Innovative cancer therapies and advances in drug development have created new
hopes for patients and health providers. The purpose of this article was to
evaluate the discrepancies in the assessment of the magnitude of benefit of four
new drugs (abiraterone acetate, enzalutamide, cabazitaxel, radium-223 dichloride)
for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The
comparison was done among three European countries (UK, Germany and France) and
Canada, according to the statement of each country and to the European Society of
Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale. Whereas those drugs
are authorized by the European Medical Agency, one can observed that clear
discrepancies in the magnitude of benefit assessment exist between selected
countries, as well as between national pricing evaluation agencies and ESMO.
However, price setting and reimbursement decisions remain national responsibility
with differences in assessment of the medical value of new treatment across
countries, leading to a heterogeneous accessibility to cancer treatments. In
conclusion, several procedures have to be implemented to overcome the patchwork
of administrative assessments. Among them, the assessment of medical value should
be based on independent statements of learned societies, and the harmonization of
access to cancer therapy in Europe has to be driven by a common European
reimbursement and pricing policy.
PMID- 28426106
TI - Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non
small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7
trial.
AB - Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib,
significantly improved progression-free survival (PFS), time-to-treatment failure
(TTF) and objective response rate (ORR) versus gefitinib in patients with
epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung
cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS)
data. Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus
gefitinib 250 mg/day in treatment-naive patients with stage IIIb/IV NSCLC and a
common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned
after ~213 OS events and >=32-month follow-up. OS was analysed by a Cox
proportional hazards model, stratified by EGFR mutation type and baseline brain
metastases. Results: Two-hundred and twenty-six OS events had occurred at the
data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS
(afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) =
0.86, 95% confidence interval (CI) 0.66-1.12, P = 0.2580]. Prespecified subgroup
analyses showed similar OS trends (afatinib versus gefitinib) in patients with
exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58-1.17, P =
0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62-1.36, P =
0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least
one subsequent systemic anti-cancer treatment following discontinuation of
afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third
generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF
and ORR data were significantly improved with afatinib. Conclusion: In LUX-Lung
7, there was no significant difference in OS with afatinib versus gefitinib.
Updated PFS (independent review), TTF and ORR data were significantly improved
with afatinib. Clinicaltrials.gov identifier: NCT01466660.
PMID- 28426108
TI - MRI assessment and outcomes in patients receiving neoadjuvant chemotherapy only
for primary rectal cancer: long-term results from the GEMCAD 0801 trial.
AB - Background: Primary chemotherapy has been tested as a possible approach for
patients with high risk features but predicted clear mesorectal margins on
preoperative MRI assessment. This study investigates the prognostic relevance of
baseline and post-treatment MRI and pathology staging in rectal cancer patients
undergoing primary chemotherapy. Patients and methods: Forty-six patients with T3
tumour > =2 mm from the mesorectal fascia were prospectively treated with
Neoadjuvant Capecitabine, Oxaliplatin and Bevacizumab prior to surgery between
2009 and 2011. The baseline and post-treatment MRI: T, Nodal and Extra-mural
venous invasion (EMVI) status were recorded as well as post-treatment MRI Tumour
regression grade (TRG) and modified-RECIST assessment of tumour length. The post
treatment pathology (yp) assessments of T3 substage, N, EMVI and TRG status were
also recorded. Three-year disease-free survival (DFS) and cumulative incidence of
recurrence were estimated by using the Kaplan-Meier product-limit method, and Cox
proportional hazards models were used to determine associations between staging
and response on MRI and pathology with survival outcomes. Results: About 46
patients underwent neoadjuvant chemotherapy alone for high risk margin safe
primary rectal cancer. The median follow-up was 41 months, 5 patients died and 11
patients experienced relapse (2 local, 8 distant and 1 both). In total 23/46
patients were identified with MRI features of EMVI at baseline. mrEMVI positive
status carried independent prognostic significance for DFS (P = 0.0097) with a
hazard ratio of 31.33 (95% CI: 2.3-425.4). The histopathologic factor that was of
independent prognostic importance was a final ypT downstage of ypT3a or less,
hazard ratio: 14.0 (95% CI: 1.5-132.5). Conclusions: mrEMVI is an independent
prognostic factor at baseline for poor outcomes in rectal cancer treated with
neoadjuvant chemotherapy while <=ypT3a is associated with an improvement in DFS.
Future preoperative therapy evaluation in rectal cancer patients will need to
stratify treatment according to baseline EMVI status as a crucial risk factor for
recurrence in patients with predicted CRM clear rectal cancer.
PMID- 28426109
TI - Defining research priorities without biases: what is the optimal process?
PMID- 28426110
TI - Closing the gap in travel medicine: reframing research questions for a new era.
AB - Background: Travel medicine needs are changing. New patterns of travel, including
greater travel by individuals from emerging economies with different values in
costs, risks and benefits, must be considered. This review aims to (1) highlight
selected studies that have been published that address previously identified gaps
in knowledge; (2) propose possible ways to consider questions regarding travel
medicine practice for travelers from emerging economies, underscoring priorities
for research focusing on these important populations; (3) highlight potential
deficiencies in relevance of current international guidelines as they pertain to
travelers from emerging economies; (4) frame research questions for travelers
from emerging economies and (5) consider roles for ISTM in closing the gap.
Methods: We reviewed past travel medicine research priorities published in 2010
to identify publications that responded to some research questions posed. We also
reviewed CDC and WHO recommendations and assessed their applicability to
travelers from emerging economies. Results: Recent publications have responded to
some research questions, but gaps remain and new questions have emerged. Re
framing of several key research questions is needed for travelers from emerging
economies. Discussion: A new challenge looms for traditional travel medicine
fields to identify and attend to knowledge and guideline gaps, particularly to
rethink questions regarding travel medicine to make them relevant for travelers
from emerging economies. The International Society of Travel Medicine is well
positioned to assist emerging economies assess their resources and needs,
formulate research priorities and tailor the development of travel medicine into
a framework aligned to their requirements.
PMID- 28426111
TI - Importation of yellow fever into China: assessing travel patterns.
AB - Rapid increase in trade and a growing air passenger market encourages high travel
volume between the regions associated with increasing risks of such importations
including China. Eleven Chinese workers infected during the 2016 yellow fever
(YF) outbreak in Angola imported YF into China highlighting the potential for
spread into Asia. Using outbound and inbound travel data, we assessed travel
patterns from and to YF endemic countries in relation to China. Among YF endemic
countries, Angola has the second highest number of travellers into China and also
receives the second highest number of Chinese visitors. We estimated that China
needs around half a million YF vaccine doses to cover their population travelling
to YF endemic countries. The recent importation cases into China also unmasked
the low YF vaccination coverage among Chinese travellers and workers to Angola,
indicating the need to ensure better adherence to the International Health
Regulations.
PMID- 28426112
TI - Travel medicine perspectives of select travel medicine experts practicing in the
Asia-Pacific region.
PMID- 28426113
TI - Health problems among Thai tourists returning from India.
AB - Background: The number of Thai tourists visiting India is increasing each year.
Most studies investigating health problems among international travellers to
India have focused on travellers from Europe or North America, and the
applicability of these studies to Asian travellers is unknown. Methods: This
cross-sectional study used data collected from Thai tourists who had recently
completed a trip to India. A questionnaire on demographic data, travel
characteristics, pre-travel health preparation, and health problems during the
trip to India was administered. All participants were also invited to answer a
follow-up questionnaire 15 days after their arrival. Results: The study included
1,304 Thai tourists returning from India between October 2014 and March 2015.
Sixty-two percent were female. Overall median age was 49 years, and the median
length of stay was 10.6 days. Most were package tourists, and 52% (675) reported
health problems during their trip. Common health problems were cough, runny nose,
and sore throat (31.1%), followed by musculoskeletal problems (21.7%), fever
(12.7%), diarrhea (9.8%) and skin problems (6.6%). Other reported problems were
related to the eyes/ears (2.1%), animal exposure (1.9%) and accidents (0.8%). We
found that several factors may be associated with the incidence of health
problems among these tourists, including travelling style and travel health
preparation. In the follow-up questionnaire, 16.8% of the participants reported
new or additional symptoms that developed after their return to Thailand.
Respiratory symptoms were still the most common health problems during this 15
day period. Conclusions: Over half (52%) of Thai tourists experienced health
problems during their trip to India. The most common health problem was not
travellers' diarrhoea, as would be expected from published studies. Rather,
respiratory and musculoskeletal problems were common symptoms. This information
will be useful in pre-travel assessment and care. Our findings may indicate that
health risks among travellers vary by nationality.
PMID- 28426114
TI - Infectious diseases and migrant worker health in Singapore: a receiving country's
perspective.
AB - Background: Approximately 1.4 million migrant workers reside in Singapore,
presenting unique infectious disease challenges to both migrants and Singapore.
Methods: A Pubmed, MEDLINE (Ovid), EBSCO Host (Global Health) and Google Scholar
search was performed for both peer, non-peer reviewed articles and reports
relevant to migrant health in Singapore, published between 1 January 1989 and 1
September 2016. Additional studies were identified from citations within searched
articles. We also reviewed published data and policy documents from the
Ministries of Health and Manpower, Singapore. Results: A significant proportion
of malaria, enteric fevers, hepatitis A and E and tuberculosis diagnosed in
Singapore involve migrant workers. From the 1990-2000 through 2009-11, while
malaria and hepatitis A cases have decreased and remain sporadic, enteric fevers
and tuberculosis cases have increased, possibly due to greater influx of migrant
workers. Hepatitis E numbers remain low but migrant workers account for half of
diagnosed cases. In an interplay of immune naivete, work and living conditions,
migrants in the construction industry are at higher risk of arboviral infections
such as dengue, Zika and chikungunya. Infections such as chikungunya were likely
introduced into Singapore by travellers including migrant workers from the Indian
subcontinent but autochthonous transmission continued due to the presence of
competent mosquito vectors. There is less data regarding sexual health, networks
and infections amongst migrant workers, an area which merits further attention.
Conclusions: Migrant workers appear to be at higher risk than Singaporeans for
specific infectious diseases, probably due to a complex interplay of several
factors, including higher disease prevalence in their countries of origin, socio
economic factors, their living conditions in Singapore and financial, language
and cultural barriers to healthcare access. Receiving countries need improved
surveillance, expansion of preventive measures and decreased barriers to
healthcare access for migrant workers.
PMID- 28426115
TI - Health problems of newly arrived migrants and refugees in Europe.
AB - Background: The number of migrants and refugees in Europe in the past few years
has increased dramatically due to war, violence or prosecutions in their
homeland. Migration may affect physical, mental and social health. The objective
of this article is to assess migrants and refugees' health problems, and to
recommend appropriate interventions. Methods: A PubMed search of published
articles on health problems of newly arrived migrants and refugees was conducted
from 2003 through 2016, focusing on the current refugee crisis in Europe.
Results: In addition to communicable diseases, such as respiratory,
gastrointestinal and dermatologic infections, non-communicable diseases,
including chronic conditions, mental and social problems, account for a
significant morbidity burden in newly arrived migrants and refugees. Vaccine
preventable diseases are also of outmost importance. The appropriate management
of newly arrived refugees and migrants' health problems is affected by barriers
to access to health care including legal, communication, cultural and
bureaucratic difficulties. There is diversity and lack of integration regarding
health care provision across Europe due to policy differences between health care
systems and social services. Conclusion: There is a notable burden of
communicable and non-communicable diseases among newly arrived migrants and
refugees. Provision of health care at reception and temporary centres should be
integrated and provided by a multidisciplinary team Appropriate health care of
migrants and refugees could greatly enhance their health and social status which
will benefit also the host countries at large.
PMID- 28426116
TI - Portuguese expatriates' health in Angola and Mozambique-a cross-sectional study:
increasing awareness and need for more surveillance.
AB - Background: Increasing numbers of expatriates are working in sub-Saharan Africa.
There is little published data on the complex population and this survey aimed at
understanding expatriate morbidity by accessing self-reported health problems and
malaria preventive practices. Methods: A cross-sectional web-based survey was
conducted targeting Portuguese expatriates in Angola and Mozambique. Logistic
regression analysis explored factors associated with self-reported health
problems and psychological symptoms in the previous 3 months. Results: A total
sample of 352 adult Portuguese urban civil occupational expatriates was obtained.
Median length of expatriation was 3 years. Considering a 3-month timeframe, one
in five expatriates reported new health problems and need of medical assistance,
5% were hospitalized and 64% reported general psychological symptoms. Less than
2% of subjects were on malaria chemoprophylaxis. Having chronic health conditions
doubled the reporting of new health problems. Increasing length of expatriation
was associated with decreasing reporting of general psychological symptoms.
Directors and executive managers and expatriates living alone tended to report
more general psychological symptoms. Conclusion: Expatriate communities deserve
enhanced surveillance for the health issues that affect them. This will improve
evidence-based preparation and intervention by public and travel health
practitioners.
PMID- 28426117
TI - Identifying the gaps in Nepalese migrant workers' health and well-being: a review
of the literature.
AB - Background: The health and well-being of migrant workers from low-income
countries is often neglected in travel medicine. This article uses Nepal as a
case study to highlight key issues affecting this particular group of
international travellers. Methods: This narrative review used a comprehensive
systematic literature search to identify relevant studies on Nepal. The included
articles were thematically analysed leading to four key themes or risk factors.
Results: The search found 18 articles from which we identified 3 key themes
related directly to migrant workers: (1) sexual risk taking; (2) occupational
health and (3) lifestyles, and a fourth theme related to partners and family of
migrant workers who are left behind in Nepal. Of the 18 included articles, 11
articles discussed sexual risk taking and HIV, whilst considerably fewer focused
on work-related risk factors and lifestyle factors in migrant workers.
Conclusions: Migrant workers who are generally healthy appear to be similar to
tourist travellers in regarding sexual health as a key issue related to being
abroad. Risky sexual behaviour increases in individuals separated from their
usual sexual partners, away from their own communities and families, leading to
the so-called 'situational disinhibition'. Considering the recent media coverage
of deaths and injuries among migrant workers in the Middle East, it is
interesting to see that their sexual health is more prevalent in the research
literature. This article argues that travel medicine should provide more emphasis
to the health and well-being of migrant workers as a highly vulnerable group of
travellers with additional impact on the health of those left behind.
PMID- 28426119
TI - Dual HER2 inhibition and pathological complete response in early breast cancer:
increasing success of treatment by improving patient selection.
PMID- 28426118
TI - Closing the gap in travel medicine.
PMID- 28426120
TI - A phase II study of a human anti-PDGFRalpha monoclonal antibody (olaratumab, IMC
3G3) in previously treated patients with metastatic gastrointestinal stromal
tumors.
AB - Background: This study evaluated tumor response to olaratumab (an anti-PDGFRalpha
monoclonal antibody) in previously treated patients with metastatic
gastrointestinal stromal tumor (GIST) with or without PDGFRalpha mutations
(cohorts 1 and 2, respectively). Patients and methods: Patients received
olaratumab 20 mg/kg intravenously every 14 days until disease progression, death,
or intolerable toxicity occurred. Outcome measures were 12-week tumor response,
progression-free survival (PFS), overall survival (OS), and safety. Results: Of
30 patients enrolled, 21 patients received >=1 dose of olaratumab. In the
evaluable population (cohort 1, n = 6; cohort 2, n = 14), no complete response
(CR) or partial response (PR) was observed. Stable disease (SD) was observed in 3
patients (50.0%) in cohort 1 and 2 patients (14.3%) in cohort 2. Progressive
disease (PD) was observed in 3 patients (50.0%) in cohort 1 and 12 patients
(85.7%) in cohort 2. The 12-week clinical benefit rate (CR + PR + SD) (90% CI)
was 50.0% (15.3-84.7%) in cohort 1 and 14.3% (2.6-38.5%) in cohort 2. SD lasted
beyond 12 weeks in 5 patients (cohort 1, n = 3; cohort 2, n = 2). Median PFS (90%
CI) was 32.1 (5.0-35.9) weeks in cohort 1 and 6.1 (5.7-6.3) weeks in cohort 2.
Median OS was not reached in cohort 1 and was 24.9 (14.4-49.1) weeks in cohort 2.
All patients in cohort 1 and 9 (64.3%) in cohort 2 experienced an olaratumab
related adverse event (AE), most commonly fatigue (38.1%), nausea (19.0%), and
peripheral edema (14.3%). Two grade >=3 olaratumab-related events were reported
(cohort 1, syncope; cohort 2, hypertension). Conclusions: Olaratumab had an
acceptable AE profile in patients with GIST. While there was no apparent effect
on PFS in patients without PDGFRalpha mutations, patients with PDGFRalpha-mutant
GIST (all with D842V mutations) treated with olaratumab had longer disease
control compared with historical data for this genotype. ClinicalTrials.gov
Identifier: NCT01316263.
PMID- 28426121
TI - Phase II study of cabazitaxel with or without abiraterone acetate and prednisone
in patients with metastatic castrate resistant prostate cancer after prior
docetaxel and abiraterone acetate.
PMID- 28426122
TI - Efficacy of androgen deprivation therapy and the role of oxidative stress.
PMID- 28426123
TI - Cabozantinib in hepatocellular carcinoma: results of a phase 2 placebo-controlled
randomized discontinuation study.
AB - Background: Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases
including MET, AXL, and VEGF receptors, was assessed in patients with
hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation
trial with nine tumor-type cohorts. Patients and methods: Eligible patients had
Child-Pugh A liver function and <=1 prior systemic anticancer regimen, completed
>=4 weeks before study entry. The cabozantinib starting dose was 100 mg daily.
After an initial 12-week cabozantinib treatment period, patients with stable
disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) version
1.0 were randomized to cabozantinib or placebo. The primary endpoint of the lead
in stage was objective response rate (ORR) at week 12, and the primary endpoint
of the randomized stage was progression-free survival (PFS). Results: Among the
41 HCC patients enrolled, the week 12 ORR was 5%, with 2 patients achieving a
confirmed partial response (PR). The week 12 disease control rate (PR or SD) was
66% (Asian subgroup: 73%). Of patients with >=1 post-baseline scan, 78% had tumor
regression, with no apparent relationship to prior sorafenib therapy. Alpha
fetoprotein (AFP) response (>50% reduction from baseline) occurred in 9 of the 26
(35%) patients with elevated baseline AFP and >=1 post-baseline measurement.
Twenty-two patients with SD at week 12 were randomized. Median PFS after
randomization was 2.5 months with cabozantinib and 1.4 months with placebo,
although this difference was not statistically significant. Median PFS and
overall survival from Day 1 in all patients were 5.2 and 11.5 months,
respectively. The most common grade 3/4 adverse events, regardless of
attribution, were diarrhea (20%), hand-foot syndrome (15%), and thrombocytopenia
(15%). Dose reductions were utilized in 59% of patients. Conclusions:
Cabozantinib has clinical activity in HCC patients, including objective tumor
responses, disease stabilization, and reductions in AFP. Adverse events were
managed with dose reductions. Trial registration number: NCT00940225.
PMID- 28426124
TI - Propofol suppresses LPS-induced nuclear accumulation of HIF-1alpha and tumor
aggressiveness in non-small cell lung cancer.
AB - Tumor hypoxia has been recognized as a characteristic of the tumor
microenvironment and promotes metastasis in a variety of types of cancer.
However, in lung cancer, the role of hypoxia-inducible factor 1alpha (HIF-1alpha)
in modulating the cellular response to the inflammation-related microenvironment
remains unclear. In the present study, enhanced expression of HIF-1alpha
accompanied by an increased ROS level was observed in lipopolysaccharide (LPS)
stimulated non-small cell lung cancer (NSCLC) cells. In addition, propofol, a
general anesthetic, was found to significantly reduce the LPS-induced
upregulation of HIF-1alpha and ROS in a dose-dependent manner. Further study
showed that propofol may antagonize the role of LPS in activating HIF-1alpha
through attenuating the protein stability and nuclear localization of HIF-1alpha.
Moreover, knockdown of HIF-1alpha attenuated expression of mesenchymal marker,
vimentin, but promoted the expression of epidermal marker, E-cadherin, in the LPS
treated NSCLC cells. Notably, LPS-induced epithelial-to-mesenchymal transition
(EMT) was notably suppressed by propofol treatment. Consistently, a wound healing
assay revealed that propofol abrogated LPS-stimulated migration of NSCLC cells
while overexpression of HIF-1alpha reversed the effects of propofol. Similarly,
we investigated the influence of propofol on the invasive capability of NSCLC
cells. Western blot and RT-PCR analyses indicated that both knockdown of HIF
1alpha and treatment of propofol attenuated the LPS-activated expression of MMP2
and MMP9 which are necessary for tumor invasion. However, results from the
Transwell assay confirmed that propofol also suppressed cell invasion by
decreasing HIF-1alpha expression in the LPS-treated NSCLC cells. Analysis of
clinical specimens demonstrated abnormal expression of HIF-1alpha in NSCLC
tissues and a poor prognosis in patients with elevated HIF-1alpha expression.
Thus, the present study suggests a potential strategy for NSCLC by targeting HIF
1alpha.
PMID- 28426125
TI - Cerclage Use: A Review of 3 National Guidelines.
AB - Importance: Preterm birth is a major contributor to perinatal morbidity and
mortality. The most common intervention performed to improve perinatal outcomes
for a woman experiencing cervical dilation in the second trimester without signs
or symptoms of preterm labor is the cerclage. Objective: We sought to review and
compare available national guidelines on cerclage use. Evidence Acquisition: We
performed a descriptive review of 3 national guidelines on cerclage: The American
Congress of Obstetricians and Gynecologists Practice Bulletin on "Cerclage for
the Management of Cervical Insufficiency," Green-top Guideline from the Royal
College of Obstetricians and Gynaecologists entitled "Cervical Cerclage," and the
Society of Obstetricians and Gynaecologists of Canada Clinical Practice Bulletin
entitled "Cervical Insufficiency and Cervical Cerclage." Guidelines were
compared, and the following aspects of cerclage use for prevention of preterm
delivery were summarized: indications and contraindications, risk factors for
cervical insufficiency, perioperative considerations, and timing of removal.
Recommendations and strength of evidence were reviewed based on each guideline's
method of reporting. The references were compared with regard to the total number
of randomized control trials, Cochrane Reviews, and systematic reviews/meta
analyses cited. Results: The variations highlighted in the guidelines reflect the
heterogeneity of the literature contributing to guidelines and the challenges of
diagnosing and managing cervical insufficiency. Conclusions: A cohesive
international guideline may improve safety and quality and optimize patient
outcomes. Target Audience: Obstetricians and gynecologists, family physicians.
Learning Objectives: After completing this activity, the learner should be better
able to outline variations in indications and contraindications for cervical
cerclage use by international guideline, identify variation in perioperative
considerations for cervical cerclage use by international guideline, and
recognize variation in timing of removal by international guideline.
PMID- 28426126
TI - Actinomyces in Pregnancy: A Review of the Literature.
AB - Importance: Actinomyces is commonly found in many areas of the body where it
derives a benefit without harming the host. When it does infect the host during
pregnancy, is that infection a threat to the obstetric patient and does that
infection cause adverse pregnancy outcomes? Objective: The aim of this study was
to review what is known about Actinomyces infections and the impact of an
Actinomyces infection on pregnancy outcomes. Evidence Acquisition: A PubMed
search was undertaken with the search years unlimited to April 1, 2016, and
restricted to articles in English. The search terms included "actinomyces,"
"pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy,"
"chorioamnionitis," "preterm labor," "premature birth," or "postpartum
actinomyces." Results: Eighteen of the 154 identified articles are the basis of
this review. Actinomyces is a rod-like positive bacterium. The diagnosis of an
Actinomyces infection can be by culture or Gram stain. Actinomyces is commensal
and typically only infects after a mucosal break or lesion. Seventeen cases were
identified in pregnancy. Ten cases were complicated by chorioamnionitis and a
preterm delivery. A nidus leading to infection was identified in 12 of the cases
including women with a cervical cerclage, dental abscesses, appendicitis, renal
actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked
with periodontal disease, but treatment did not prevent preterm delivery in a
randomized, blinded, controlled trial. Conclusions: Actinomyces infections in
pregnancy are rare but, if they occur, have been linked primarily with preterm
deliveries. Target Audience: Obstetricians and gynecologists, family physicians.
Learning Objectives: After completing this activity, the learner should be better
able to identify the areas of the body where Actinomyces infections occur and how
the infections typically occur, identify the pathophysiologic changes that occur
during pregnancy that might lead to an Actinomyces infection and how that
infection may affect pregnancy outcomes, and describe the treatment for mild and
severe Actinomyces infections.
PMID- 28426127
TI - Postpartum Hypertension: Etiology, Diagnosis, and Management.
AB - Importance: Postpartum hypertension complicates approximately 2% of pregnancies
and, similar to antepartum severe hypertension, can have devastating consequences
including maternal death. Objective: This review aims to increase the knowledge
and skills of women's health care providers in understanding, diagnosing, and
managing hypertension in the postpartum period. Results: Hypertension
complicating pregnancy, including postpartum, is defined as systolic blood
pressure 140 mm Hg or greater and/or diastolic blood pressure 90 mm Hg or greater
on 2 or more occasions at least 4 hours apart. Severe hypertension is defined as
systolic blood pressure 160 mm Hg or greater and/or diastolic blood pressure 110
mm Hg or greater on 2 or more occasions repeated at a short interval (minutes).
Workup for secondary causes of hypertension should be pursued, especially in
patients with severe or resistant hypertension, hypokalemia, abnormal creatinine,
or a strong family history of renal disease. Because severe hypertension is known
to cause maternal stroke, women with severe hypertension sustained over 15
minutes during pregnancy or in the postpartum period should be treated with fast
acting antihypertension medication. Labetalol, hydralazine, and nifedipine are
all effective for acute management, although nifedipine may work the fastest. For
persistent postpartum hypertension, a long-acting antihypertensive agent should
be started. Labetalol and nifedipine are also both effective, but labetalol may
achieve control at a lower dose with fewer adverse effects. Conclusions and
Relevance: Providers must be aware of the risks associated with postpartum
hypertension and educate women about the symptoms of postpartum preeclampsia.
Severe acute hypertension should be treated in a timely fashion to avoid
morbidity and mortality. Women with persistent postpartum hypertension should be
administered a long-acting antihypertensive agent. Target Audience: Obstetricians
and gynecologists, family physicians. Learning Objectives: After completing this
activity, the learner should be better able to assist patients and providers in
identifying postpartum hypertension; provide a framework for the evaluation of
new-onset postpartum hypertension; and provide instructions for the management of
acute severe and persistent postpartum hypertension.
PMID- 28426128
TI - Hippocampal electrical stimulation disrupts associative learning when targeted at
dentate spikes.
AB - KEY POINTS: Dentate spikes are fast fluctuations of hilar local-field potentials
that take place during rest and are thought to reflect input arriving from the
entorhinal cortex to the hippocampus. During dentate spikes, neuronal firing in
hippocampal input (dentate gyrus) and output (CA1/CA3) regions is uncoupled. To
date, the behavioural significance of dentate spikes is unknown. Here, we provide
evidence that disrupting the dentate spike-related uncoupling of the dentate
gyrus and the CA1/CA3 subregions for 1 h after training retards associative
learning. We suggest dentate spikes play a significant role in memory
consolidation. ABSTRACT: Hippocampal electrophysiological oscillations, namely
theta and ripples, have been implicated in encoding and consolidation of new
memories, respectively. According to existing literature, hippocampal dentate
spikes are prominent, short-duration (<30 ms), large-amplitude (~2-4 mV)
fluctuations in hilar local-field potentials that take place during awake
immobility and sleep. Interestingly, previous studies indicate that during
dentate spikes dentate gyrus granule cells increase their firing while firing of
CA1 pyramidal cells are suppressed, thus resulting in momentary uncoupling of the
two hippocampal subregions. To date, the behavioural significance of dentate
spikes is unknown. Here, to study the possible role of dentate spikes in
learning, we trained adult male Sprague-Dawley rats in trace eyeblink classical
conditioning. For 1 h immediately following each conditioning session, one group
of animals received hippocampal stimulation via the ventral hippocampal
commissure (vHC) contingent on dentate spikes to disrupt the uncoupling between
the dentate gyrus and the CA1 subregions. A yoked control group was stimulated
during immobility, irrespective of brain state, and another control group was not
stimulated at all. As a result, learning was impaired only in the group where vHC
stimulation was administered contingent on dentate spikes. Our results suggest
dentate spikes and/or the associated uncoupling of the dentate gyrus and the CA1
play a significant role in memory consolidation. Dentate spikes could possibly
reflect reactivation and refinement of a memory trace within the dentate gyrus
triggered by input from the entorhinal cortex.
PMID- 28426129
TI - Case review and outcomes of prenatally diagnosed amniotic sheets.
PMID- 28426130
TI - Length of stay for patients undergoing invasive electrode monitoring with
stereoelectroencephalography and subdural grids correlates positively with
increased institutional profitability.
AB - OBJECTIVE: Lowering the length of stay (LOS) is thought to potentially decrease
hospital costs and is a metric commonly used to manage capacity. Patients with
epilepsy undergoing intracranial electrode monitoring may have longer LOS because
the time to seizure is difficult to predict or control. This study investigates
the effect of economic implications of increased LOS in patients undergoing
invasive electrode monitoring for epilepsy. METHODS: We retrospectively collected
and analyzed patient data for 76 patients who underwent invasive monitoring with
either subdural grid (SDG) implantation or stereoelectroencephalography (SEEG)
over 2 years at our institution. Data points collected included invasive
electrode type, LOS, profit margin, contribution margins, insurance type, and
complication rates. RESULTS: LOS correlated positively with both profit and
contribution margins, meaning that as LOS increased, both the profit and
contribution margins rose, and there was a low rate of complications in this
patient group. This relationship was seen across a variety of insurance
providers. SIGNIFICANCE: These data suggest that LOS may not be the best metric
to assess invasive monitoring patients (i.e., SEEG or SDG), and increased LOS
does not necessarily equate with lower or negative institutional financial gain.
Further research into LOS should focus on specific specialties, as each may
differ in terms of financial implications.
PMID- 28426131
TI - Sonographic appearance of proliferative fasciitis---A case report.
AB - Proliferative fasciitis is a benign entity involving the subcutaneous tissues and
fascias, characterized by the proliferation of fibroblast-like spindle cells and
ganglion-like cells. However, proliferative fasciitis may be easily confused with
sarcoma clinically and pathologically, because it appears as a rapidly growing
painful mass and has histologic features such as high cellularity, bizarre
morphologic patterns, mitotic figures, and diffuse infiltrative proliferation.
Imaging findings of proliferative fasciitis have been very rarely reported. We
report the sonographic findings in a case of proliferative fasciitis in a 43-year
old woman with histopathological correlation. (c) 2017 Wiley Periodicals, Inc. J
Clin Ultrasound 45:445-449, 2017.
PMID- 28426132
TI - A parasitoid wasp's odd pupal vigil.
PMID- 28426133
TI - Quantitative phase microscopy spatial signatures of cancer cells.
AB - We present cytometric classification of live healthy and cancerous cells by using
the spatial morphological and textural information found in the label-free
quantitative phase images of the cells. We compare both healthy cells to primary
tumor cells and primary tumor cells to metastatic cancer cells, where tumor
biopsies and normal tissues were isolated from the same individuals. To mimic
analysis of liquid biopsies by flow cytometry, the cells were imaged while
unattached to the substrate. We used low-coherence off-axis interferometric phase
microscopy setup, which allows a single-exposure acquisition mode, and thus is
suitable for quantitative imaging of dynamic cells during flow. After
acquisition, the optical path delay maps of the cells were extracted and then
used to calculate 15 parameters derived from the cellular 3D morphology and
texture. Upon analyzing tens of cells in each group, we found high statistical
significance in the difference between the groups in most of the parameters
calculated, with the same trends for all statistically significant parameters.
Furthermore, a specially designed machine learning algorithm, implemented on the
phase map extracted features, classified the correct cell type
(healthy/cancer/metastatic) with 81-93% sensitivity and 81-99% specificity. The
quantitative phase imaging approach for liquid biopsies presented in this paper
could be the basis for advanced techniques of staging freshly isolated live
cancer cells in imaging flow cytometers. (c) 2017 International Society for
Advancement of Cytometry.
PMID- 28426134
TI - Metastasis detection from whole slide images using local features and random
forests.
AB - Digital pathology has led to a demand for automated detection of regions of
interest, such as cancerous tissue, from scanned whole slide images. With
accurate methods using image analysis and machine learning, significant speed-up,
and savings in costs through increased throughput in histological assessment
could be achieved. This article describes a machine learning approach for
detection of cancerous tissue from scanned whole slide images. Our method is
based on feature engineering and supervised learning with a random forest model.
The features extracted from the whole slide images include several local
descriptors related to image texture, spatial structure, and distribution of
nuclei. The method was evaluated in breast cancer metastasis detection from lymph
node samples. Our results show that the method detects metastatic areas with high
accuracy (AUC = 0.97-0.98 for tumor detection within whole image area, AUC = 0.84
0.91 for tumor vs. normal tissue detection) and that the method generalizes well
for images from more than one laboratory. Further, the method outputs an
interpretable classification model, enabling the linking of individual features
to differences between tissue types. (c) 2017 International Society for
Advancement of Cytometry.
PMID- 28426135
TI - TLR-Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In
Vivo.
AB - Eosinophils like many myeloid innate immune cells can provide cytokines and
chemokines for the activation of other immune cells upon TLR stimulation. When
TLR-stimulated eosinophils were inoculated i.p. into wild-type mice, and NK cells
were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice
depleted of CD11c+ cells were used, a marked decrease in the number of recruited
NK cells was observed. We postulated that CpG or LPS from the injected
eosinophils could be transferred to host cells, which in turn could recruit NK
cells. However, by inoculating mice deficient in TLR4 or TLR9 with LPS or CpG
stimulated eosinophils respectively, NK cell recruitment was still observed
alongside cytotoxicity and IFNgamma production. CpG stimulation of eosinophils
produced the pro-inflammatory cytokine IL-12 and the chemokine CXCL10, which are
important for NK cell activation and recruitment in vivo. To demonstrate the
importance of CXCL10 in NK cell recruitment, we found that CpG-stimulated
eosinophils pretreated with the gut microbial metabolite butyrate had reduced
expression and production of CXCL10 and IL-12 and concomitantly were poor at
recruitment of NK cells and inducing IFNgamma in NK cells. Therefore, eosinophils
like other innate immune cells of myeloid origin can conceivably stimulate NK
cell activity. In addition, products of the gut microbiota can be potential
inhibitors of NK cell.
PMID- 28426136
TI - Differentiating signals to make biological sense - A guide through databases for
MS-based non-targeted metabolomics.
AB - Metabolite identification is one of the most challenging steps in metabolomics
studies and reflects one of the greatest bottlenecks in the entire workflow. The
success of this step determines the success of the entire research, therefore the
quality at which annotations are given requires special attention. A variety of
tools and resources are available to aid metabolite identification or annotation,
offering different and often complementary functionalities. In preparation for
this article, almost 50 databases were reviewed, from which 17 were selected for
discussion, chosen for their online ESI-MS functionality. The general
characteristics and functions of each database is discussed in turn, considering
the advantages and limitations of each along with recommendations for optimal use
of each tool, as derived from experiences encountered at the Centre for
Metabolomics and Bioanalysis (CEMBIO) in Madrid. These databases were evaluated
considering their utility in non-targeted metabolomics, including aspects such as
identifier assignment, structural assignment and interpretation of results.
PMID- 28426137
TI - Hydroxyurea (hydroxycarbamide) for sickle cell disease.
AB - BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited
diseases worldwide. It is associated with lifelong morbidity and a reduced life
expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug,
ameliorates some of the clinical problems of SCD, in particular that of pain, by
raising fetal haemoglobin. This is an update of a previously published Cochrane
Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with
SCD (all genotypes), of any age, regardless of setting. SEARCH METHODS: We
searched the Cochrane Cystic Fibrosis and Genetic Disorders Group
Haemoglobinopathies Register, comprising of references identified from
comprehensive electronic database searches and handsearches of relevant journals
and abstract books of conference proceedings. We also searched online trial
registries.Date of the most recent search: 16 January 2017. SELECTION CRITERIA:
Randomised and quasi-randomised controlled trials, of one month or longer,
comparing hydroxyurea with placebo, standard therapy or other interventions for
people with SCD. DATA COLLECTION AND ANALYSIS: Authors independently assessed
studies for inclusion, carried out data extraction and assessed the risk of bias.
MAIN RESULTS: Seventeen studies were identified in the searches; eight randomised
controlled trials were included, recruiting 899 adults and children with SCD
(haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sbetaothalassaemia
(HbSbetaothal) genotypes). Studies lasted from six to 30 months.Four studies (577
adults and children with HbSS or HbSbetaothal) compared hydroxyurea to placebo;
three recruited individuals with only severe disease and one recruited
individuals with all disease severities. There were statistically significant
improvements in terms of pain alteration (using measures such as pain crisis
frequency, duration, intensity, hospital admissions and opoid use), measures of
fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest
syndrome and blood transfusions in the hydroxyurea groups. There were no
consistent statistically significant differences in terms of quality of life and
adverse events (including serious or life-threatening events). Seven deaths
occurred during the studies, but the rates by treatment group were not
statistically significantly different.Two studies (254 children with HbSS or
HbSbetaothal also with risk of primary or secondary stroke) compared hydroxyurea
and phlebotomy to transfusion and chelation; there were statistically significant
improvements in terms of measures of fetal haemoglobin and neutrophil counts, but
more occurrences of acute chest syndrome and infections in the hydroxyurea and
phlebotomy group. There were no consistent statistically significant differences
in terms of pain alteration and adverse events (including serious or life
threatening events). Two deaths occurred during the studies (one in a the
hydroxyurea treatment arm and one in the control arm), but the rates by treatment
group were not statistically significantly different. In the primary prevention
study, no strokes occurred in either treatment group but in the secondary
prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group
(none in the transfusion and chelation group) and the study was terminated
early.The quality of the evidence for the above two comparisons was judged as
moderate to low as the studies contributing to these comparisons were mostly
large and well designed (and at low risk of bias); however evidence was limited
and imprecise for some outcomes such as quality of life, deaths during the
studies and adverse events and results are applicable only to individuals with
HbSS and HbSbetaothal genotypes.Of the remaining two studies, one (22 children
with HbSS or HbSbetaothal also at risk of stoke) compared hydroxyurea to
observation; there were statistically significant improvements in terms of
measures of fetal haemoglobin and neutrophil counts but no statistically
significant differences in terms of adverse events (including serious or life
threatening events).The final study (44 adults and children with HbSC) compared
treatment regimens with and without hydroxyurea - there was statistically
significant improvement in terms of measures of fetal haemoglobin, but no
statistically significant differences in terms of adverse events (including
serious or life-threatening events). No participants died in either of these
studies and other outcomes relevant to the review were not reported.The quality
of the evidence for the above two comparisons was judged to be very low due to
the limited number of participants, the lack of statistical power (as both
studies were terminated early with approximately only 20% of their target sample
size recruited) and the lack of applicability to all age groups and genotypes.
AUTHORS' CONCLUSIONS: There is evidence to suggest that hydroxyurea is effective
in decreasing the frequency of pain episodes and other acute complications in
adults and children with sickle cell anaemia of HbSS or HbSbetaothal genotypes
and in preventing life-threatening neurological events in those with sickle cell
anaemia at risk of primary stroke by maintaining transcranial doppler velocities.
However, there is still insufficient evidence on the long-term benefits of
hydroxyurea, particularly in preventing chronic complications of SCD,
recommending a standard dose or dose escalation to maximum tolerated dose. There
is also insufficient evidence about the long-term risks of hydroxyurea, including
its effects on fertility and reproduction. Evidence is also limited on the
effects of hydroxyurea on individuals with HbSC genotype. Future studies should
be designed to address such uncertainties.
PMID- 28426138
TI - Incremental burden of cardiovascular comorbidity and psoriatic arthritis among
adults with moderate-to-severe psoriasis in five European countries.
AB - BACKGROUND: Moderate-to-severe psoriasis is associated with reduced health
related quality of life (HRQoL). Individuals with psoriasis are at increased risk
for other medical conditions, but little information quantifies the incremental
burden of psoriasis-associated comorbidity among European adults, and data have
generally been limited to clinical samples. OBJECTIVE: To quantify the
incremental burden of cardiovascular comorbidity and psoriatic arthritis among
adults with moderate-to-severe psoriasis in the general population of France,
Germany, Italy, Spain and the United Kingdom (EU5). METHODS: All measures were
self-reported and came from the 2010-2013 EU5 National Health and Wellness
Surveys (NHWS). Moderate-to-severe psoriasis was identified by >10% body surface
area affected by psoriasis and/or use of therapies for moderate-severe disease.
Outcomes were SF-12v2/SF-36v2 mental and physical component summary scores (MCS
and PCS, respectively), SF-6D health utility, Work Productivity and Activity
Impairment (WPAI) questionnaire and healthcare use in the past 6 months.
Generalized linear models compared across cardiovascular comorbidity (CV) or
psoriatic arthritis (PsA) groups vs. non-CV or non-PsA groups with appropriate
link functions to adjust for covariates. RESULTS: Among moderate-to-severe
psoriasis respondents (n = 957), 19.8% (n = 190) reported CV comorbidity and
12.3% (n = 118) reported PsA. After adjustment for covariates, CV comorbidity was
associated with 3.0 points lower MCS, 3.4 points lower PCS and 0.05 points lower
SF-6D (all P < 0.01). Likewise, they had greater mean work impairment (48% vs.
33%), more activity impairment (48% vs. 37%), and more healthcare provider visits
(8.8 vs. 6.9), emergency room visits (0.65 vs. 0.31) and hospitalizations (0.61
vs. 0.22) (all P < 0.05). Compared to non-PsA respondents, PsA respondents also
had worse mean MCS (2.6 points), PCS (6.3 points) and SF-6D scores (0.07 points),
and more work impairment (52% vs. 34%), activity impairment (54% vs. 38%) and
healthcare provider visits (10.5 vs. 6.9) (all P < 0.05). CONCLUSION: CV
comorbidity and PsA were associated with significant incremental burden among EU5
adults with moderate-to-severe psoriasis.
PMID- 28426139
TI - Engineering a Promiscuous Tautomerase into a More Efficient Aldolase for Self
Condensations of Linear Aliphatic Aldehydes.
AB - The enzyme 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 takes
part in a catabolic pathway for aromatic hydrocarbons, where it catalyzes the
conversion of 2hydroxyhexa-2,4-dienedioate into 2-oxohexa-3-enedioate. This
tautomerase can also promiscuously catalyze carbon-carbon bond-forming reactions,
including various types of aldol reactions, by using its amino-terminal proline
as a key catalytic residue. Here, we used systematic mutagenesis to identify two
hotspots in 4-OT (Met45 and Phe50) at which single mutations give marked
improvements in aldolase activity for the self-condensation of propanal. Activity
screening of a focused library in which these two hotspots were varied led to the
discovery of a 4-OT variant (M45Y/F50V) with strongly enhanced aldolase activity
in the self-condensation of linear aliphatic aldehydes, such as acetaldehyde,
propanal, and butanal, to yield alpha,beta-unsaturated aldehydes. With both
propanal and benzaldehyde, this double mutant, unlike the previously constructed
single mutant F50A, mainly catalyzes the self-condensation of propanal rather
than the cross-condensation of propanal and benzaldehyde, thus indicating that it
indeed has altered substrate specificity. This variant could serve as a template
to create new biocatalysts that lack dehydration activity and possess further
enhanced aldolase activity, thus enabling the efficient enzymatic self-coupling
of aliphatic aldehydes.
PMID- 28426140
TI - Stomatal kinetics and photosynthetic gas exchange along a continuum of isohydric
to anisohydric regulation of plant water status.
AB - Species' differences in the stringency of stomatal control of plant water
potential represent a continuum of isohydric to anisohydric behaviours. However,
little is known about how quasi-steady-state stomatal regulation of water
potential may relate to dynamic behaviour of stomata and photosynthetic gas
exchange in species operating at different positions along this continuum. Here,
we evaluated kinetics of light-induced stomatal opening, activation of
photosynthesis and features of quasi-steady-state photosynthetic gas exchange in
10 woody species selected to represent different degrees of anisohydry. Based on
a previously developed proxy for the degree of anisohydry, species' leaf water
potentials at turgor loss, we found consistent trends in photosynthetic gas
exchange traits across a spectrum of isohydry to anisohydry. More anisohydric
species had faster kinetics of stomatal opening and activation of photosynthesis,
and these kinetics were closely coordinated within species. Quasi-steady-state
stomatal conductance and measures of photosynthetic capacity and performance were
also greater in more anisohydric species. Intrinsic water-use efficiency
estimated from leaf gas exchange and stable carbon isotope ratios was lowest in
the most anisohydric species. In comparisons between gas exchange traits, species
rankings were highly consistent, leading to species-independent scaling
relationships over the range of isohydry to anisohydry observed.
PMID- 28426141
TI - Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8+ T
Cytotoxic Lymphocytes and CD19+ B Lymphocytes in Rheumatoid Arthritis Responding
to TNF-alpha Inhibition.
AB - Melanocortin signalling in leucocyte subsets elicits anti-inflammatory and immune
tolerance inducing effects in animal experimental inflammation. In man, however,
the effects of melanocortin signalling in inflammatory conditions have scarcely
been examined. We explored the differential reactions of melanocortin 1-5
receptors (MC1-5R) gene expressions in pathogenetic leucocyte subsets in
rheumatoid arthritis (RA) to treatment with TNF-alpha inhibitor adalimumab. Seven
patients with active RA donated blood at start and at 3-month treatment. CD4+ T
helper (h) lymphocytes (ly), CD8+ T cytotoxic (c) ly, CD19+ B ly and CD14+
monocytes were isolated, using immunomagnetic beads, total RNA extracted and
reverse transcription quantitative polymerase chain reaction (RT-qPCR) performed.
Fold changes in MC1-5R, Th1-, inflammatory- and regulatory cytokine gene
expressions were assessed for correlation. Six patients responded to adalimumab
treatment, while one patient was non-responder. In all lymphocyte subtypes, MC1
5R gene expressions decreased in responders and increased in the non-responder.
In responders, decrease in MC2R, MC3R and MC4R gene expressions in CD8+ Tc and
CD19+ B ly was significant. Fold change in MC1-5R and IFNgamma gene expressions
correlated significantly in CD8+ Tc ly, while fold change in MC1R, MC3R and MC5R
and IL-1beta gene expressions correlated significantly in CD4+ Th ly. Our results
show regulation of MC2R, MC3R and MC4R gene expressions in CD8+ Tc ly and CD19+ B
ly. The correlations between fold change in different MCRs and disease driving
cytokine gene expressions in CD8+ Tc ly and CD4+ Th ly point at a central immune
modulating function of the melanocortin system in RA.
PMID- 28426142
TI - Integrated care in cancer: What is it, how is it used and where are the gaps? A
textual narrative literature synthesis.
AB - Integrated care is an underpinning concept of contemporary health care policy
proffered as a strategy to overcome the fragmentations in care encountered by
people with complex care needs (Shaw et al. [2011] What is Integrated Care? An
Overview of Integrated Care in the NHS). Cancer patients have potential to
benefit from such policy, often having needs that extend beyond cancer. This
paper seeks to understand how the concept of integrated care is used in the
cancer literature. A search of leading databases was conducted for original
research relating to integrated care or an integration intervention aiming to
improve outcomes of cancer patients, and analysed using textual narrative
synthesis. 38 papers were included, each with a focus on improving cancer
specific aspects of care enhancing the capabilities of the cancer
multidisciplinary team. Of the eight studies involving integration between the
cancer service and other care providers, all focused on utilising the external
provider to deliver aspects of cancer care or placed them in a passive role, as
survey participant, a recipient of cancer-related clinical information or as the
comparator "usual care" arm. Within the cancer literature, integration is
predominantly used to describe initiatives to improve cancer-related aspects of
care. Less attention is given to integration initiatives that enhance
coordination across levels of the healthcare system or service providers.
PMID- 28426143
TI - Coronal Transcranial Sonography and M-Mode Tremor Frequency Determination in
Parkinson's Disease and Essential Tremor.
AB - BACKGROUND AND PURPOSE: The axial mesencephalic transcranial sonography plane is
an established and sensitive diagnostic tool for the differentiation of
Parkinson's disease and essential tremor. However, the substantia nigra can also
be depicted in a second coronal examination plane, whose diagnostic value has not
yet been evaluated. Furthermore, the M-mode tremor frequency determination
represents another sonographic tool, which might yield additional diagnostic
value. METHODS: We included patients with diagnosed Parkinson's disease (n = 31),
essential tremor (n = 16), and healthy age-matched controls (n = 16). All were
examined by transcranial sonography in the axial and coronal plane. Tremor
frequencies were quantified by an M-mode tremor frequency determination
examination protocol. A clinical assessment was conducted in all participants.
RESULTS: The utilization of a coronal examination plane improved the diagnostic
strength in discriminating of Parkinson's disease from essential tremor and
healthy controls. In combination with the determination of tremor frequency, best
discriminative results were achieved (sensitivity, 90.3%; specificity, 96.9%). In
the Parkinson's disease group, we found a significant positive correlation
between hyposmia and coronal hyperechogenicity. CONCLUSION: The combined usage of
coronal transcranial sonography and M-mode tremor frequency determination should
be considered to improve diagnostic strength of sonographic techniques for the
diagnosis of Parkinson's disease.
PMID- 28426144
TI - A multiplex culture system for the long-term growth of fission yeast cells.
AB - Maintenance of long-term cultures of yeast cells is central to a broad range of
investigations, from metabolic studies to laboratory evolution assays. However,
repeated dilutions of batch cultures lead to variations in medium composition,
with implications for cell physiology. In Saccharomyces cerevisiae, powerful
miniaturized chemostat setups, or ministat arrays, have been shown to allow for
constant dilution of multiple independent cultures. Here we set out to adapt
these arrays for continuous culture of a morphologically and physiologically
distinct yeast, the fission yeast Schizosaccharomyces pombe, with the goal of
maintaining constant population density over time. First, we demonstrated that
the original ministats are incompatible with growing fission yeast for more than
a few generations, prompting us to modify different aspects of the system design.
Next, we identified critical parameters for sustaining unbiased vegetative growth
in these conditions. This requires deletion of the gsf2 flocculin-encoding gene,
along with addition of galactose to the medium and lowering of the culture
temperature. Importantly, we improved the flexibility of the ministats by
developing a piezo-pump module for the independent regulation of the dilution
rate of each culture. This made it possible to easily grow strains that have
different generation times in the same assay. Our system therefore allows for
maintaining multiple fission yeast cultures in exponential growth, adapting the
dilution of each culture over time to keep constant population density for
hundreds of generations. These multiplex culture systems open the door to a new
range of long-term experiments using this model organism. (c) 2017 The Authors.
Yeast published by John Wiley & Sons, Ltd.
PMID- 28426145
TI - Subunit Vaccines Consisting of Antigens from Dormant and Replicating Bacteria
Show Promising Therapeutic Effect against Mycobacterium Bovis BCG Latent
Infection.
AB - To screen effective antigens as therapeutic subunit vaccines against
Mycobacterium latent infection, we did bioinformatics analysis and literature
review to identify effective antigens and evaluated the immunogenicity of five
antigens highly expressed in dormant bacteria, which included Rv2031c (HspX),
Rv2626c (Hrp1), Rv2007c (FdxA), Rv1738 and Rv3130c. Then, several fusion proteins
such as Rv2007c-Rv2626c (F6), Rv2031c-Rv1738-Rv1733c (H83), ESAT6-Rv1738-Rv2626c
(LT40), ESAT6-Ag85B-MPT64<190-198> -Mtb8.4 (EAMM), and EAMM-Rv2626c (LT70) were
constructed and their therapeutic effects were evaluated in pulmonary
Mycobacterium bovis Bacilli Calmette-Guerin (BCG) - latently infected rabbit or
mouse models. The results showed that EAMM and F6 plus H83 had therapeutic effect
against BCG latent infection in the rabbit model, respectively, and that the
combination of EAMM with F6 plus H83 significantly reduced the bacterial load. In
addition, the fusion proteins LT40 and LT70 consisting of multistage antigens
showed promising therapeutic effects in the mouse model. We conclude that subunit
vaccines consisting of both latency and replicating-associated antigens show
promising therapeutic effects in BCG latent infection animal models.
PMID- 28426146
TI - The influence of substance use on depressive symptoms among young adult black
men: The sensitizing effect of early adversity.
AB - BACKGROUND AND OBJECTIVES: Depressive symptoms have been identified as an
important consequence of substance use. Both heavy drinking and marijuana use
have acute and short-term effects on systems that regulate emotion, increasing
the potential for substance use to induce problems with negative affect and
irritability. We investigated the effects of alcohol and marijuana use on
depressive symptoms among a sample of young Black men. We also tested the stress
sensitization hypothesis that exposure to adverse childhood experiences would
amplify the influence of substance use on men's depressive symptoms. METHODS:
Hypotheses were tested with 505 rural Black men who, at ages 19-22 years,
provided data on their substance use, adverse childhood experiences, and
depressive symptoms; they provided data again 18 months later. RESULTS: Substance
use forecasted increases in depressive symptoms; cross-lagged analyses yielded no
evidence for the inverse path, depressive symptoms increasing substance use. The
impact of substance use on depressive symptoms was amplified among young Black
men who were exposed to adverse childhood experiences. Substance use did not
significantly predict depressive symptoms when adversity was low. DISCUSSION AND
CONCLUSIONS: Our findings suggest that, during young adulthood, substance use
increases depressive symptoms among Black men who were exposed to childhood
adversity. Because childhood adversity disproportionately affects Black men,
these findings inform future cross-group research designed to investigate racial
disparities in the consequences of substance use. SCIENTIFIC SIGNIFICANCE:
Depressive symptoms may be understood as an effect as well as a cause of
substance use, particularly among vulnerable young Black men. (Am J Addict
2017;26:400-406).
PMID- 28426147
TI - Propagation of error from parameter constraints in quantitative MRI: Example
application of multiple spin echo T2 mapping.
AB - PURPOSE: Quantitative MRI may require correcting for nuisance parameters which
can or must be constrained to independently measured or assumed values. The noise
and/or bias in these constraints propagate to fitted parameters. For example, the
case of refocusing pulse flip angle constraint in multiple spin echo T2 mapping
is explored. METHODS: An analytical expression for the mean-squared error of a
parameter of interest was derived as a function of the accuracy and precision of
an independent estimate of a nuisance parameter. The expression was validated by
simulations and then used to evaluate the effects of flip angle (theta)
constraint on the accuracy and precision of T?2 for a variety of multi-echo T2
mapping protocols. RESULTS: Constraining theta improved T?2 precision when the
theta-map signal-to-noise ratio was greater than approximately one-half that of
the first spin echo image. For many practical scenarios, constrained fitting was
calculated to reduce not just the variance but the full mean-squared error of
T?2, for bias in theta??6%. CONCLUSION: The analytical expression derived in this
work can be applied to inform experimental design in quantitative MRI. The
example application to T2 mapping provided specific cases, depending on theta?
accuracy and precision, in which theta? measurement and constraint would be
beneficial to T?2 variance or mean-squared error. Magn Reson Med 79:673-682,
2018. (c) 2017 International Society for Magnetic Resonance in Medicine.
PMID- 28426148
TI - Three-dimensional finite-element based deformable image registration for
evaluation of pleural cavity irradiation during photodynamic therapy.
AB - PURPOSE: Photodynamic therapy (PDT) is used after surgical resection to treat the
microscopic disease for malignant pleural mesothelioma and to increase survival
rates. As accurate light delivery is imperative to PDT efficacy, the deformation
of the pleural volume during the surgery is studied on its impact on the
delivered light fluence. In this study, a three-dimensional finite element-based
(3D FEM) deformable image registration is proposed to directly match the volume
of lung to the volume of pleural cavity obtained during PDT to have accurate
representation of the light fluence accumulated in the lung, heart and liver
(organs-at-risk) during treatment. METHODS: A wand, comprised of a modified
endotrachial tube filled with Intralipid and an optical fiber inside the tube, is
used to deliver the treatment light. The position of the treatment is tracked
using an optical tracking system with an attachment comprised of nine reflective
passive markers that are seen by an infrared camera-based navigation system. This
information is used to obtain the surface contours of the plural cavity and the
cumulative light fluence on every point of the cavity surface that is being
treated. The lung, heart, and liver geometry are also reconstructed from a series
of computed tomography (CT) scans of the organs acquired in the same patient
before and after the surgery. The contours obtained with the optical tracking
system and CTs are imported into COMSOL Multiphysics, where the 3D FEM-based
deformable image registration is obtained. The delivered fluence values are
assigned to the respective positions (x, y, and z) on the optical tracking
contour. The optical tracking contour is considered as the reference, and the CT
contours are used as the target, which will be deformed. The data from three
patients formed the basis for this study. RESULTS: The physical correspondence
between the CT and optical tracking geometries, taken at different times, from
different imaging devices was established using the 3D FEM-based image deformable
registration. The volume of lung was matched to the volume of pleural cavity and
the distribution of light fluence on the surface of the heart, liver and deformed
lung volumes was obtained. CONCLUSION: The method used is appropriate for
analyzing problems over complicated domains, such as when the domain changes (as
in a solid-state reaction with a moving boundary), when the desired precision
varies over the entire domain, or when the solution lacks smoothness.
Implementing this method in real-time for clinical applications and in situ
monitoring of the under- or over- exposed regions to light during PDT can
significantly improve the treatment for mesothelioma.
PMID- 28426149
TI - Click-Chemistry-Mediated Rapid Microbubble Capture for Acute Thrombus Ultrasound
Molecular Imaging.
AB - Bioorthogonal coupling chemistry has been studied as a potentially advantageous
approach for molecular imaging because it offers rapid, efficient, and strong
binding, which might also benefit stability, production, and chemical
conjugation. The inverse-electron-demand Diels-Alder reaction between a 1,2,4,5
tetrazine and trans-cyclooctene (TCO) is an example of a highly selective and
rapid bioorthogonal coupling reaction that has been used successfully to prepare
targeted molecular imaging probes. Here we report a fast, reliable, and highly
sensitive approach, based on a two-step pretargeting bioorthogonal approach, to
achieving activated-platelet-specific CD62p-targeted thrombus ultrasound
molecular imaging. Tetrazine-modified microbubbles (tetra-MBs) could be uniquely
and rapidly captured by subsequent click chemistry of thrombus tagged with a
trans-cyclooctene-pretreated CD62p antibody. Moreover, such tetra-MBs showed
great long-term stability under physiological conditions, thus offering the
ability to monitor thrombus changes in real time. We demonstrated for the first
time that a bioorthogonal targeting molecular ultrasound imaging strategy based
on tetra-MBs could be a simple but powerful tool for rapid diagnosis of acute
thrombosis.
PMID- 28426150
TI - Measurements of morphological and biophysical alterations in individual neuron
cells associated with early neurotoxic effects in Parkinson's disease.
AB - Parkinson's disease (PD) is a common neurodegenerative disease. However,
therapeutic methods of PD are still limited due to complex pathophysiology in PD.
Here, optical measurements of individual neurons from in vitro PD model using
optical diffraction tomography (ODT) are presented. By measuring 3D refractive
index distribution of neurons, morphological and biophysical alterations in in
vitro PD model are quantitatively investigated. It was found that neurons show
apoptotic features in early PD progression. The present approach will open up new
opportunities for quantitative investigation of the pathophysiology of various
neurodegenerative diseases. (c) 2017 International Society for Advancement of
Cytometry.
PMID- 28426151
TI - Ammonothermal Synthesis of Earth-Abundant Nitride Semiconductors ZnSiN2 and
ZnGeN2 and Dissolution Monitoring by In Situ X-ray Imaging.
AB - In this contribution, first synthesis of semiconducting ZnSiN2 and ZnGeN2 from
solution is reported with supercritical ammonia as solvent and KNH2 as
ammonobasic mineralizer. The reactions were conducted in custom-built high
pressure autoclaves made of nickel-based superalloy. The nitrides were
characterized by powder X-ray diffraction and their crystal structures were
refined by the Rietveld method. ZnSiN2 (a=5.24637(4), b=6.28025(5), c=5.02228(4)
A, Z=4, Rwp =0.0556) and isotypic ZnGeN2 (a=5.46677(10), b=6.44640(12),
c=5.19080(10) A, Z=4, Rwp =0.0494) crystallize in the orthorhombic space group
Pna21 (no. 33). The morphology and elemental composition of the nitrides were
examined by electron microscopy and energy-dispersive X-ray spectroscopy (EDX).
Well-defined single crystals with a diameter up to 7 MUm were grown by
ammonothermal synthesis at temperatures between 870 and 1070 K and pressures up
to 230 MPa. Optical properties have been analyzed with diffuse reflectance
measurements. The band gaps of ZnSiN2 and ZnGeN2 were determined to be 3.7 and
3.2 eV at room temperature, respectively. In situ X-ray measurements were
performed to exemplarily investigate the crystallization mechanism of ZnGeN2 .
Dissolution in ammonobasic supercritical ammonia between 570 and 670 K was
observed which is quite promising for the crystal growth of ternary nitrides
under ammonothermal conditions.
PMID- 28426152
TI - Donor-specific alloreactive T cells can be quantified from whole blood, and may
predict cellular rejection after renal transplantation.
AB - Preformed cellular alloreactivity can exist prior to transplantation and may
contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay
to characterize the extent of alloreactive T cells among 1491 stimulatory
reactions from 61 renal transplant candidates and 75 controls. The role of
preformed donor-specific alloreactive T cells in cellular rejection was
prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8+ T
cells were more frequent than respective CD4+ T cells, and these levels were
stable over time. CD8+ T cells were effector-memory T cells largely negative for
expression of CD27, CD62L, and CCR7, and were susceptible to steroid and
calcineurin inhibitor inhibition. Alloreactivity was more frequent in samples
with higher number of HLA mismatches. Moreover, the percentage of individuals
with alloreactive T cells was higher in transplant candidates than in controls.
Among transplant candidates, 5/61 exhibited alloreactive CD8+ T cells against
most stimulators, 23/61 toward a limited number of stimulators, and 33/61 did not
show any alloreactivity. Among 21 renal transplant recipients followed
prospectively, one had donor-specific preformed T-cell alloreactivity. She was
the only patient who developed cellular rejection posttransplantation. In
conclusion, donor-specific alloreactive T cells may be rapidly quantified from
whole blood, and may predict cellular rejection after transplantation.
PMID- 28426153
TI - A Non-pathogenic Recombinant Leishmania Expressing Lipophosphoglycan 3 Against
Experimental Infection with Leishmania infantum.
AB - Visceral leishmaniasis (VL) is caused by Leishmania infantum in the Mediterranean
basin and affects primarily children and immunosuppressed individuals. Various
strategies of vaccination have so far been examined by either protein or DNA
without achievable complete protection against the disease. The live non
pathogenic lizard parasite, Leishmania tarentolae, expressing elected Leishmania
antigens has recently provided a promising new approach as a safe and effective
live vaccine candidate to prevent leishmaniasis. Here, we evaluated the
immunoprotective potential of a live recombinant L. tarentolae expressing
Lipophosphoglycan 3 (LPG3) antigen against L. infantum infection in BALB/c mice.
Results indicated that the administration of live recombinant Leishmania produced
a significant high level of IFN-gamma accompanied by reduced levels of IL-10 as
compared to wild-type parasites as live vaccine control, thus suggesting the
induction of a Th1-type immune response in a mouse model of visceral
leishmaniasis. Analysis of the IgG antibody response also showed high levels of
IgG2a relative to IgG1 in sera of mice immunized with recombinant Leishmania
parasites. However, immune responses elicited by this live vaccine conferred
partial protection against infectious challenge. Therefore, further studies are
required to increase its protective efficacy.
PMID- 28426154
TI - Transparent and Gas-Permeable Liquid Marbles for Culturing and Drug Sensitivity
Test of Tumor Spheroids.
AB - Transparent nanoparticle-based liquid marbles with high gas-permeability are
prepared to culture tumor spheroids in 3D without the need of supplementary
growth factor. The culturing process of spheroids from a population of cancer
cells or a single cell in the transparent liquid marbles can be optically
recorded continuously. Compared to monolayer cells and spheroids generated in
multiwell plate, tumor spheroids cultured in the liquid marbles show enhanced
viability under the treatment of chemotherapeutic drugs and small interfering
RNA.
PMID- 28426155
TI - Insect transmission of plant viruses: Multilayered interactions optimize viral
propagation.
AB - By serving as vectors of transmission, insects play a key role in the infection
cycle of many plant viruses. Viruses use sophisticated transmission strategies to
overcome the spatial barrier separating plants and the impediment imposed by the
plant cell wall. Interactions among insect vectors, viruses, and host plants
mediate transmission by integrating all organizational levels, from molecules to
populations. Best-examined on the molecular scale are two basic transmission
modes wherein virus-vector interactions have been well characterized. Whereas
association of virus particles with specific sites in the vector's mouthparts or
in alimentary tract regions immediately posterior to them is required for
noncirculative transmission, the cycle of particles through the vector body is
necessary for circulative transmission. Virus transmission is also determined by
interactions that are associated with changes in vector feeding behaviors and
with alterations in plant host's morphology and/or metabolism that favor the
attraction or deterrence of vectors. A recent concept in virus-host-vector
interactions proposes that when vectors land on infected plants, vector elicitors
and effectors "inform" the plants of the confluence of interacting entities and
trigger signaling pathways and plant defenses. Simultaneously, the plant
responses may also influence virus acquisition and inoculation by vectors.
Overall, a picture is emerging where transmission depends on multilayered virus
vector-host interactions that define the route of a virus through the vector, and
on the manipulation of the host and the vector. These interactions guarantee
virus propagation until one or more of the interactants undergo changes through
evolution or are halted by environmental interventions.
PMID- 28426156
TI - Natural terpene derivatives as new structural task-specific ionic liquids to
enhance the enantiorecognition of acidic enantiomers on teicoplanin-based
stationary phase by high-performance liquid chromatography.
AB - We present the specific cooperative effect of a semisynthetic glycopeptide
antibiotic teicoplanin and chiral ionic liquids containing the (1R,2S,5R)-(-)
menthol moiety on the chiral recognition of enantiomers of mandelic acid,
vanilmandelic acid, and phenyllactic acid. Experiments were performed
chromatographically on an Astec Chirobiotic T chiral stationary phase applying
the mobile phase with the addition of the chiral ionic liquids. The
stereoselective binding of enantiomers to teicoplanin in presence of new chiral
ionic liquids were evaluated applying thermodynamic measurements and the docking
simulations. Both the experimental and theoretical methods revealed that the
chiral recognition of enantiomers in the presence of new chiral ionic liquids was
enthalpy driven. The changes of the teicoplanin conformation occurring upon
binding of the chiral ionic liquids are responsible for the differences in the
standard changes in Gibbs energy (DeltaG0 ) values obtained for complexes formed
by the R and S enantiomers and teicoplanin. Docking simulations revealed the
steric adjustment between the chiral ionic liquids cyclohexane ring (chair
conformation) and the beta-d-glucosamine ring of teicoplanin and additionally
hydrophobic interactions between the decanoic aliphatic chain of teicoplanin and
the alkyl group of the tested salts. The obtained terpene derivatives can be
considered as "structural task-specific ionic liquids" responsible for enhancing
the chiral resolution in synergistic systems with two chiral selectors.
PMID- 28426157
TI - Effects of ambient temperature in association with photoperiod on phenology and
on the expressions of major plant developmental genes in wheat (Triticum aestivum
L.).
AB - In addition to its role in vernalization, temperature is an important
environmental stimulus in determining plant growth and development. We used
factorial combinations of two photoperiods (16H, 12H) and three temperature
levels (11, 18 and 25 degrees C) to study the temperature responses of 19 wheat
cultivars with established genetic relationships. Temperature produced more
significant effects on plant development than photoperiod, with strong genotypic
components. Wheat genotypes with PPD-D1 photoperiod sensitive allele were
sensitive to temperature; their development was delayed by higher temperature,
which intensified under non-inductive conditions. The effect of temperature on
plant development was not proportional; it influenced the stem elongation to the
largest extent, and warmer temperature lengthened the lag phase between the
detection of first node and the beginning of intensive stem elongation. The gene
expression patterns of VRN1, VRN2 and PPD1 were also significantly modified by
temperature, while VRN3 was more chronologically regulated. The associations
between VRN1 and VRN3 gene expression with early apex development were
significant in all treatments but were only significant for later plant
developmental phases under optimal conditions (16H and 18 degrees C). Under 16H,
the magnitude of the transient peak expression of VRN2 observed at 18 and 25
degrees C associated with the later developmental phases.
PMID- 28426158
TI - A novel technique for decellularization of allogenic nerves and in vivo study of
their use for peripheral nerve reconstruction.
AB - Autografts represent the gold standard for peripheral nerve reconstruction but
their limited availability, the discrepancy of nerve caliber, and long surgical
times are drawbacks. Allografts have therefore become a valid alternative option.
In particular, acellular nerve allografts (ANAs) rather than fresh allografts do
not need immunosuppression and appear to be safe and effective based on recent
studies. An innovative method was conceived to obtain ANAs, so as to speed up
nerve decellularization, without compromising nerve architecture, and without
breaking the asepsis chain. Several detergent-based techniques, integrated with
sonication and mechanical stirring, were tested in vitro on rabbit nerves, to
identify, by microscopy and immunohistochemistry, the most effective protocol in
terms of cell lysis and cellular debris clearance, while maintaining nerve
architecture. Furthermore, a pilot in vivo study was performed: ANAs were
implanted into tibial nerve defects of three rabbits, and autografts,
representing the gold standard, in other three animals. Twelve weeks
postoperatively, rabbits were clinically evaluated and euthanasized; grafts were
harvested and microscopically and histomorphometrically analyzed. The method
proved to be effective in vitro: the treatment removed axons, myelin and cells,
without altering nerve architecture. The in vivo study did not reveal any adverse
effect: animals maintained normal weight and function of posterior limb during
the entire experimental time. A mild fibrotic reaction was observed, macrophages
and leukocytes were rare or absent; ANAs regenerated fascicles and bundles were
comparable versus autografts. Based on these results, this decellularization
protocol is encouraging and deserves deeper investigations with further
preclinical and clinical studies. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
Res Part A: 105A: 2228-2240, 2017.
PMID- 28426159
TI - Open microfluidic gel electrophoresis: Rapid and low cost separation and analysis
of DNA at the nanoliter scale.
AB - Gel electrophoresis is one of the most applied and standardized tools for
separation and analysis of macromolecules and their fragments in academic
research and in industry. In this work we present a novel approach for conducting
on-demand electrophoretic separations of DNA molecules in open microfluidic (OM)
systems on planar polymer substrates. The approach combines advantages of slab
gel, capillary- and chip-based methods offering low consumable costs (<0.1$)
circumventing cost-intensive microfluidic chip fabrication, short process times
(5 min per analysis) and high sensitivity (4 ng/MUL dsDNA) combined with
reasonable resolution (17 bases). The open microfluidic separation system
comprises two opposing reservoirs of 2-4 MUL in volume, a semi-contact written
gel line acting as separation channel interconnecting the reservoirs and sample
injected into the line via non-contact droplet dispensing and thus enabling the
precise control of the injection plug and sample concentration. Evaporation is
prevented by covering aqueous structures with PCR-grade mineral oil while
maintaining surface temperature at 15 degrees C. The liquid gel line exhibits a
semi-circular cross section of adaptable width (~200-600 MUm) and height (~30-80
MUm) as well as a typical length of 15-55 mm. Layout of such liquid structures is
adaptable on-demand not requiring time consuming and repetitive fabrication
steps. The approach was successfully demonstrated by the separation of a standard
label-free DNA ladder (100-1000 bp) at 100 V/cm via in-line staining and laser
induced fluorescent end-point detection using an automated prototype.
PMID- 28426160
TI - Assessment and support during early labour for improving birth outcomes.
AB - BACKGROUND: The progress of labour in the early or latent phase is usually slow
and may include painful uterine contractions. Women may feel distressed and lose
their confidence during this phase. Support and assessment interventions have
been assessed in two previous Cochrane Reviews. This review updates and replaces
these two reviews, which have become out of date. OBJECTIVES: To investigate the
effectiveness of assessment and support interventions for women during early
labour.In order to measure the effectiveness of the interventions, we compared
the duration of labour, the rate of obstetrical interventions, and the rate of
other maternal or neonatal outcomes. SEARCH METHODS: We searched the Cochrane
Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World
Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
(31 October 2016) and reference lists of retrieved studies. SELECTION CRITERIA:
Randomised controlled trials of any assessment or support intervention in the
latent phase of labour. We planned to include cluster-randomised trials if they
were eligible. We did not include quasi-randomised trials. DATA COLLECTION AND
ANALYSIS: Two review authors independently assessed trials for inclusion and risk
of bias, extracted data and checked them for accuracy. We resolved any
disagreement by discussion or by involving a third assessor. The quality of the
evidence was assessed using the GRADE approach. MAIN RESULTS: We included five
trials with a total of 10,421 pregnant women in this review update. The trials
were conducted in the UK, Canada and America. The trials compared interventions
in early labour versus usual care. We examined three comparisons: early labour
assessment versus immediate admission to hospital; home visits by midwives versus
usual care (telephone triage); and one-to-one structured midwifery care versus
usual care. These trials were at moderate- risk of bias mainly because blinding
women and staff to these interventions is not generally feasible. For important
outcomes we assessed evidence using GRADE; we downgraded evidence for study
design limitations, imprecision, and where we carried out meta-analysis, for
inconsistency.One trial with 209 women compared early labour assessment with
direct admission to hospital. Duration of labour from the point of hospital
admission was reduced for women in the assessment group (mean difference (MD)
5.20 hours, 95% confidence interval (CI) -7.06 to -3.34; 209 women, low-quality
evidence). There were no clear differences between groups for the number of women
undergoing caesarean section or instrumental vaginal birth (risk ratio (RR) 0.72,
95% CI 0.30 to 1.72, very low quality evidence; and, RR 0.86, 95% CI 0.58 to
1.26, very low quality evidence, respectively). Serious maternal morbidity was
not reported. Women in the early assessment group were slightly less likely to
have epidural anaesthesia (RR 0.87, 95% CI 0.78 to 0.98, low-quality evidence),
and considerably less likely to have oxytocin for labour augmentation (RR 0.57,
95% CI 0.37 to 0.86) and this group also had increased satisfaction with their
care compared with women in the immediate admission group (MD 16.00, 95% CI 7.53
to 24.47). No babies were born before admission to hospital and only one infant
had a low Apgar score at five minutes after the birth (very low quality
evidence). Admission to neonatal special care was not reported.Three studies
examined home assessment and midwifery support versus telephone triage. One trial
reported the duration of labour; home visits did not appear to have any clear
impact compared with usual care (MD 0.29 hours, 95% CI -0.14 to 0.72; 1 trial,
3474 women, low-quality evidence). There was no clear difference for the rate of
caesarean section (RR 1.05, 95% CI 0.95 to 1.17; 3 trials, 5170 women; I2 = 0%;
moderate-quality evidence) or the rate of instrumental vaginal birth (average RR
0.95, 95% CI 0.79 to 1.15; 2 trials, 4933 women; I2 = 69%; low-quality evidence).
One trial reported birth before arrival at hospital or unplanned home birth;
there was no clear difference between the groups (RR 1.33, 95% CI 0.30 to 5.95; 1
trial, 3474 women). No clear differences were identified for serious maternal
morbidity (RR 0.93, 95% CI 0.61 to 1.42; 1 trial, 3474 women; low-quality
evidence), or use of epidural (average RR 0.95, 95% CI 0.87 to 1.05; 3 trials,
5168 women; I2 = 60%; low-quality evidence). There were no clear differences for
neonatal admission to special care (average RR 0.84, 95% CI 0.50 to 1.42; 3
trials, 5170 infants; I2 = 71%; very low quality evidence), or for Apgar score
less than seven at five minutes after birth (RR 1.19, 95% CI 0.71 to 1.99; 3
trials, 5170 infants; I2 = 0%; low-quality evidence).One study, with 5002 women,
examined one-to-one structured care in early labour versus usual care. Length of
labour was not reported. There were no clear differences between groups for the
rate of caesarean section (RR 0.93, 95% CI 0.84 to 1.02; 4996 women, high-quality
evidence), or for instrumental vaginal birth (RR 0.94, 95% CI 0.82 to 1.08; 4996
women, high-quality evidence). No clear differences between groups were reported
for serious maternal morbidity (RR 1.13, 95% CI 0.84 to 1.52; 4996 women,
moderate-quality evidence). Use of epidural was similar in the two groups (RR
1.00, 95% CI 0.99 to 1.01; 4996 women, high-quality evidence). For infant
outcomes, there were no clear differences between groups (admission to neonatal
intensive care unit: RR 0.98, 95% CI 0.80 to 1.21; 4989 infants, high-quality
evidence; Apgar score less than seven at five minutes: RR 1.07, 95% CI 0.64 to
1.79; 4989 infants, moderate-quality evidence). AUTHORS' CONCLUSIONS: Assessment
and support in early labour does not have a clear impact on rate of caesarean
section or instrumental vaginal birth, or whether the baby was born before
arrival at hospital or in an unplanned home birth. However, evidence suggested
that interventions may have an impact on reducing the use of epidural
anaesthesia, labour augmentation and on increasing maternal satisfaction with
giving birth. Evidence about the effectiveness of early labour assessment versus
immediate admission was very limited and more research is needed in this area.
PMID- 28426163
TI - Lipid Flip-Flop and Pore Nucleation on Zwitterionic Bilayers are Asymmetric under
Ionic Imbalance.
AB - Lipid flip-flop and its associated transient pore formation are key thermodynamic
properties of living cell membranes. However, there is a lack of understanding of
whether ionic imbalance that exists ubiquitously across cell membranes affects
lipid flip-flop and its associated functions. Potential of mean force
calculations show that the free-energy barrier of lipid flip-flop on the
extracellular leaflet reduces with the presence of ionic imbalance, whereas the
barrier on the intracellular leaflet is generally not affected. The linear
decrease of the activation energy of lipid flip-flop on the extracellular leaflet
is consistent with the experimentally measured conductance-voltage relationship
of zwitterionic lipid bilayers. This suggests: 1) lipid flip-flop has a
directionality under physiological conditions and phospholipids accumulate at a
rate on the order of 105 um-2 h-1 on the cytoplasmic side of cell membranes; 2)
ion permeation across a lipid membrane is moderated by lipid flip-flop; 3) the
energy barrier of pore formation is aligned with the weaker leaflet that has a
lower energy of lipid flip-flop. The asymmetry of lipid flip-flop and pore
nucleation may have substantial implications for protein translocation,
signaling, enzymatic activities, vesicle fusion, and transportation of
biomolecules on cell membranes.
PMID- 28426162
TI - Motion-corrected simultaneous cardiac positron emission tomography and coronary
MR angiography with high acquisition efficiency.
AB - PURPOSE: Develop a framework for efficient free-breathing simultaneous whole
heart coronary magnetic resonance angiography (CMRA) and cardiac positron
emission tomography (PET) on a 3 Tesla PET-MR system. METHODS: An acquisition
that enables nonrigid motion correction of both CMRA and PET has been developed.
The proposed method estimates translational motion from low-resolution 2D MR
image navigators acquired at each heartbeat and 3D nonrigid respiratory motion
between different respiratory bins from the CMRA data itself. Estimated motion is
used for correcting the CMRA as well as the emission and attenuation PET data
sets to the same respiratory position. The CMRA approach was studied in 10
healthy subjects and compared for both left and right coronary arteries (LCA,
RCA) against a reference scan with diaphragmatic navigator gating and tracking.
The PET-CMRA approach was tested in 5 oncology patients with 18 F-FDG myocardial
uptake. PET images were compared against uncorrected and gated PET
reconstructions. RESULTS: For the healthy subjects, no statistically significant
differences in vessel length and sharpness (P > 0.01) were observed between the
proposed approach and the reference acquisition with navigator gating and
tracking, although data acquisition was significantly shorter. The proposed
approach improved CMRA vessel sharpness by 37.9% and 49.1% (LCA, RCA) and vessel
length by 48.0% and 36.7% (LCA, RCA) in comparison with no motion correction for
all the subjects. Motion-corrected PET images showed improved sharpness of the
myocardium compared to uncorrected reconstructions and reduced noise compared to
gated reconstructions. CONCLUSION: Feasibility of a new respiratory motion
compensated simultaneous cardiac PET-CMRA acquisition has been demonstrated. Magn
Reson Med 79:339-350, 2018. (c) 2017 The Authors Magnetic Resonance in Medicine
published by Wiley Periodicals, Inc. on behalf of International Society for
Magnetic Resonance in Medicine. This is an open access article under the terms of
the Creative Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited.
PMID- 28426164
TI - Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in B
cells via upregulating Bcl2L12 in patients with allergic rhinitis.
AB - BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10
cell) is compromised in patients with allergic diseases. Protease-activated
receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate
the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.
METHODS: Peripheral blood B cells were collected from patients with allergic
rhinitis (AR). A correlation between the expression of Bcl2-like protein 12
(Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.
RESULTS: We observed that the expression of IL-10 was lower in the peripheral B
cells from patients with airway allergy. A negative correlation was identified
between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B
cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10
expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B
cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the
capability of IL-10 expression and the immunosuppressive function. Administration
of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.
CONCLUSIONS: Activation of PAR2 inhibits the expression of IL-10 in B cells,
which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes.
The data suggest that regulation of Bcl2L12 may be a novel approach in the
treatment for AR.
PMID- 28426165
TI - Hydrogen peroxide-dependent antibacterial action of Melilotus albus honey.
AB - : Honey originating from different floral sources exhibits the broad spectrum of
antibacterial activity as a result of the presence of hydrogen peroxide as well
as nonperoxide bioactive compounds. The mechanisms of antibacterial activity of
Polish melilot honey were investigated for the first time. Polish melilot honey
samples (Melilotus albus biennial = 3 and annual = 5, Melilotus officinalis = 1)
were collected directly from beekeepers and analysed for pollen profile, basic
physicochemical parameters, antioxidant capacity, radical scavenging activity,
total phenolic contents as well as antibacterial properties against pathogenic
bacteria Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae,
Salmonella spp. The physicochemical properties of melilot honey were specific for
light-coloured unifloral honey samples and were not dependent on its botanical
and geographical origin (P > 0.05). All tested honey samples exhibited inhibitory
activity (above 90%) against Gram-positive bacteria at the concentration of 12.5
25%. Above 30-50% of antibacterial activity of melilot honey was connected with
glucose oxidase enzyme action and was destroyed in the presence of catalase.
Hydrogen peroxide-dependent antibacterial activity of honey was inversely
correlated with its radical scavenging activity (r = -0.67) and phenolic
compounds (r = -0.61). Antibacterial action of melilot honey depends not only on
hydrogen peroxide produced by glucose oxidase, but also on other nonperoxide
bioactive components of honey. SIGNIFICANCE AND IMPACT OF THE STUDY: Melilot
honey is used in traditional medicine as an anticoagulant agent due to the
possibility of the presence of the coumarin compounds which are specific for
Melilotus plant. Melilotus albus is rarely used to produce honey, and
antibacterial properties of this variety of honey had not been studied yet. Nine
samples of melilot honey produced in different regions of Poland were analysed
according to their antibacterial activity which was correlated with
physiochemical parameters and antioxidant activity. It was shown that
antibacterial activity of melilot honey is created by hydrogen peroxide and other
bioactive compounds.
PMID- 28426166
TI - Acute effects of radiofrequency electromagnetic field emitted by mobile phone on
brain function.
AB - Due to its attributes, characteristics, and technological resources, the mobile
phone (MP) has become one of the most commonly used communication devices.
Historically, ample evidence has ruled out the substantial short-term impact of
radiofrequency electromagnetic field (RF-EMF) emitted by MP on human cognitive
performance. However, more recent evidence suggests potential harmful effects
associated with MP EMF exposure. The aim of this review is to readdress the
question of whether the effect of MP EMF exposure on brain function should be
reopened. We strengthen our argument focusing on recent neuroimaging and
electroencephalography studies, in order to present a more specific analysis of
effects of MP EMF exposure on neurocognitive function. Several studies indicate
an increase in cortical excitability and/or efficiency with EMF exposure, which
appears to be more prominent in fronto-temporal regions and has been associated
with faster reaction time. Cortical excitability might also underpin disruption
to sleep. However, several inconsistent findings exist, and conclusions regarding
adverse effects of EMF exposure are currently limited. It also should be noted
that the crucial scientific question of the effect of longer-term MP EMF exposure
on brain function remains unanswered and essentially unaddressed.
Bioelectromagnetics. 38:329-338, 2017. (c) 2017 Wiley Periodicals, Inc.
PMID- 28426167
TI - Characterization the carotenoid productions and profiles of three Rhodosporidium
toruloides mutants from Agrobacterium tumefaciens-mediated transformation.
AB - The red yeast Rhodosporidium toruloides is a known lipid producer capable of
accumulating large amounts of triacylglycerols and carotenoids. However, it
remains challenging to study its carotenoid production profiles owing to limited
biochemical information and inefficient genetic tools. Here we used an
Agrobacterium tumefaciens-mediated transformation (ATMT) to change its carotenoid
production and profiles. We constructed R. toruloides NP11 mutant libraries with
ATMT, selected three mutants with different colours, characterized their
carotenoid products by high-pressure liquid chromatography-mass spectrometry
(HPLC-MS) analysis and assured differences among those strains in terms of
carotenoid production and its composition profiles. We then located T-DNA
insertion sites using the genome walking technology and provided discussions in
terms of the new phenotypes. This study is the first of its kind to change the
carotenoid production profiles in R. toruloides. Copyright (c) 2017 John Wiley &
Sons, Ltd.
PMID- 28426168
TI - Walking a Fine Line with Sucrose Phosphorylase: Efficient Single-Step
Biocatalytic Production of l-Ascorbic Acid 2-Glucoside from Sucrose.
AB - The 2-O-alpha-d-glucoside of l-ascorbic acid (AA-2G) is a highly stabilized form
of vitamin C, with important industrial applications in cosmetics, food, and
pharmaceuticals. AA-2G is currently produced through biocatalytic glucosylation
of l-ascorbic acid from starch-derived oligosaccharides. Sucrose would be an
ideal substrate for AA-2G synthesis, but it lacks a suitable transglycosidase. We
show here that in a narrow pH window (pH 4.8-6.0, with sharp optimum at pH 5.2),
sucrose phosphorylases catalyzed the 2-O-alpha-glucosylation of l-ascorbic acid
from sucrose with high efficiency and perfect site-selectivity. Optimized
synthesis with the enzyme from Bifidobacterium longum at 40 degrees C gave a
concentrated product (155 g L-1 ; 460 mm), from which pure AA-2G was readily
recovered in ~50 % overall yield, thus providing the basis for advanced
production. The peculiar pH dependence is suggested to arise from a "reverse
protonation" mechanism in which the catalytic base Glu232 on the glucosyl-enzyme
intermediate must be protonated for attack on the anomeric carbon from the 2
hydroxyl of the ionized l-ascorbate substrate.
PMID- 28426169
TI - Microsecond Dynamics in Ubiquitin Probed by Solid-State 15 N NMR Spectroscopy
R1rho Relaxation Experiments under Fast MAS (60-110 kHz).
AB - 15 N R1rho relaxation experiments in solid-state NMR spectroscopy are sensitive
to timescales and amplitudes of internal protein motions in the hundreds of nano-
to microsecond time window, which is difficult to probe by solution-state NMR
spectroscopy. By using 15 N R1rho relaxation experiments, a simplified approach
to detect low microsecond protein dynamics is described and residue-specific
correlation times are determined from the ratio of 15 N R1rho rate constants at
different magic angle spinning frequencies. Microcrystalline ubiquitin exhibits
small-amplitude dynamics on a timescale of about 1 MUs across the entire protein,
and larger amplitude motions, also on the 1 MUs timescale, for several sites,
including the beta1 -beta2 turn and the N terminus of the alpha helix. According
to the analysis, the microsecond protein backbone dynamics are of lower amplitude
than that concluded in previous solid-state NMR spectroscopy studies, but persist
across the entire protein with a rather uniform timescale of 1 MUs.
PMID- 28426170
TI - Detecting cancer in primary care: Where does early diagnosis stop and
overdiagnosis begin?
PMID- 28426171
TI - Sputum basophils are increased in eosinophilic asthma compared with non
eosinophilic asthma phenotypes.
AB - Sputum basophil numbers are increased in allergic asthmatics, but it is unclear
what role airway basophils play in "TH2-low" asthma phenotypes. Using flow
cytometry, we found that basophils were significantly increased in all asthmatics
(n=26) compared with healthy controls (n=8) (P=0.007) with highest levels
observed in eosinophilic asthma (EA); median 0.22%, IQR 0.11%-0.47%; n=14)
compared with non-EA (NEA) (0.06%, 0.00%-0.20%; n=12; P<0.05). In asthmatics,
basophils were positively correlated with sputum eosinophils (r=0.54; P<0.005)
and inversely with sputum neutrophils (r=-0.46: P<0.05), but not with FEV1 (%
predicted), FEV1 /FVC or bronchodilator reversibility. In a subgroup initially
identified as inadequately controlled asthma (n=7), there was a trend (P=0.08)
towards a reduction in sputum basophils following increased inhaled
corticosteroid (ICS) treatment. Our findings suggest that basophils may be
particularly important in eosinophilic asthma and that sputum basophil assessment
could be a useful additional indicator of "TH2-high" asthma.
PMID- 28426172
TI - Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with
the Presentation of Paucibacillary Leprosy and Leprosy Reactions.
AB - It is well established that helper T cell responses influence resistance or
susceptibility to Mycobacterium leprae infection, but the role of more recently
described helper T cell subsets in determining severity is less clear. To
investigate the involvement of Th17 cells in the pathogenesis of leprosy, we
determined the immune profile with variant presentations of leprosy. Firstly, IL
17A, IFN-gamma and IL-10 were evaluated in conjunction with CD4+ T cell staining
by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous
leprosy (LL) patients. Secondly, inflammatory cytokines were measured by
multiplex assay of serum samples from Multibacillary (MB, n = 28) and
Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23).
Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n
= 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed
by flow cytometry used to determine the phenotype of cytokine-producing cells.
Lesions from TT patients were found to have more CD4+ IL-17A+ cells than those
from LL patients. Higher concentrations of IL-17A and IL-1beta were observed in
serum from PB than MB patients. The highest serum IFN-gamma concentrations were,
however, detected in sera from MB patients that developed leprosy reactions (MB
LR+ ). Together, these results indicate that Th1 cells were associated with both
the PB presentation and also with leprosy reactions. In contrast, Th17 cells were
associated with an effective inflammatory response that is present in the PB
forms but were not predictive of leprosy reactions in MB patients.
PMID- 28426173
TI - Spinal Arachnoid Diverticula: Outcome in 96 Medically or Surgically Treated Dogs.
AB - BACKGROUND: Little is reported about the role of medical management in the
treatment of spinal arachnoid diverticula (SAD) in dogs. OBJECTIVES: To describe
the outcome of 96 dogs treated medically or surgically for SAD. ANIMALS: Ninety
six dogs with SAD. METHODS: Retrospective case series. Medical records were
searched for spinal arachnoid diverticula and all dogs with information on
treatment were included. Outcome was assessed with a standardized questionnaire.
RESULTS: Fifty dogs were managed medically and 46 dogs were treated surgically.
Dogs that underwent surgery were significantly younger than dogs that received
medical management. No other variables, related to clinical presentation, were
significantly different between both groups of dogs. The median follow-up time
was 16 months (1-90 months) in the medically treated and 23 months (1-94 months)
in the surgically treated group. Of the 38 dogs treated surgically with available
long-term follow-up, 82% (n = 31) improved, 3% (n = 1) remained stable and 16% (n
= 6) deteriorated after surgery. Of the 37 dogs treated medically with available
long-term follow-up, 30% (n = 11) improved, 30% (n = 11) remained stable, and 40%
(n = 15) deteriorated. Surgical treatment was more often associated with clinical
improvement compared to medical management (P = .0002). CONCLUSIONS AND CLINICAL
IMPORTANCE: The results of this study suggest that surgical treatment might be
superior to medical treatment in the management of SAD in dogs. Further studies
with standardized patient care are warranted.
PMID- 28426174
TI - Solid-Phase Synthesis of a Seventh-Generation Inverse Poly(amidoamine) Dendrimer:
Importance of the Loading Ratio on the Resin.
AB - Here, this study overcomes the current barriers to efficient solid-phase
synthesis of high-generation dendrimers by decreasing the loading ratio on the
resin. G7 inverse poly(amidoamine) dendrimer is now prepared, for the first time,
through a solid-phase synthesis using only 50% of the available reactive sites
and by choosing a large resin. This preparation takes only 15 d to afford highly
pure product in 80% yield with precipitation being the only purification
procedure used. The results clearly show the amount of the initial monomer loaded
on the resin to be a vital factor for the ability to use solid-phase synthesis to
produce large dendrimers. This finding also sets stage for the applications of
solid-phase synthesis for the preparation of other macromolecules.
PMID- 28426175
TI - Differences in xylem and leaf hydraulic traits explain differences in drought
tolerance among mature Amazon rainforest trees.
AB - Considerable uncertainty surrounds the impacts of anthropogenic climate change on
the composition and structure of Amazon forests. Building upon results from two
large-scale ecosystem drought experiments in the eastern Brazilian Amazon that
observed increases in mortality rates among some tree species but not others, in
this study we investigate the physiological traits underpinning these
differential demographic responses. Xylem pressure at 50% conductivity (xylem-P50
), leaf turgor loss point (TLP), cellular osmotic potential (pio ), and cellular
bulk modulus of elasticity (epsilon), all traits mechanistically linked to
drought tolerance, were measured on upper canopy branches and leaves of mature
trees from selected species growing at the two drought experiment sites. Each
species was placed a priori into one of four plant functional type (PFT)
categories: drought-tolerant versus drought-intolerant based on observed
mortality rates, and subdivided into early- versus late-successional based on
wood density. We tested the hypotheses that the measured traits would be
significantly different between the four PFTs and that they would be spatially
conserved across the two experimental sites. Xylem-P50 , TLP, and pio , but not
epsilon, occurred at significantly higher water potentials for the drought
intolerant PFT compared to the drought-tolerant PFT; however, there were no
significant differences between the early- and late-successional PFTs. These
results suggest that these three traits are important for determining drought
tolerance, and are largely independent of wood density-a trait commonly
associated with successional status. Differences in these physiological traits
that occurred between the drought-tolerant and drought-intolerant PFTs were
conserved between the two research sites, even though they had different soil
types and dry-season lengths. This more detailed understanding of how xylem and
leaf hydraulic traits vary between co-occuring drought-tolerant and drought
intolerant tropical tree species promises to facilitate a much-needed improvement
in the representation of plant hydraulics within terrestrial ecosystem and
biosphere models, which will enhance our ability to make robust predictions of
how future changes in climate will affect tropical forests.
PMID- 28426176
TI - UHPLC-MS/MS method for the simultaneous quantitation of five anthraquinones and
gallic acid in rat plasma after oral administration of prepared rhubarb decoction
and its application to a pharmacokinetic study in normal and acute blood stasis
rats.
AB - Prepared rhubarb, as one of the main processed products of rhubarb, has a good
effect on promoting blood circulation. In this paper we describe a rapid,
sensitive, and selective ultra-fast liquid chromatography with tandem mass
spectrometry method for simultaneous quantification of five anthraquinones
(rhein, aloe-emodin, chrysophanol, emodin, and physcion) and gallic acid in
plasma. Chromatographic separation was performed on an Extend C18 column at the
temperature of 30 degrees C using a mobile phase that consisted of 0.1% aqueous
formic acid and acetonitrile. Satisfactory linearity, precision, accuracy,
extraction recovery, and matrix effect have been achieved. Then, the validated
method was successfully applied to a comparative pharmacokinetic study. The
results might be helpful for guiding clinical application of prepared rhubarb in
the future.
PMID- 28426177
TI - An efficient cleanup method coupled with gas chromatography and mass spectrometry
for multi-pesticides residue analysis in complex plant matrices.
AB - We aimed to develop an efficient cleanup method for multi-pesticides residue
analysis in complex plant matrices, shallot, ginger, garlic, onion, leek, and
celery. Column chromatography was used as the cleanup method and fabricated with
florisil and graphitized carbon black as the adsorbents. The amount of the
graphitized carbon black adsorbent and the choice of the elution solvent were
systematically investigated for exploring the best combination. The target
pesticides covered organochlorine, pyrethroid, and organophosphorus pesticides,
and were 38 in total. The method validation and comparison were performed to
verify its feasibility and advantages in operation convenience and purification
efficiency. The method limit of quantitation varied from 0.01 to 0.03 mg/kg,
which depends on the pesticides and the sample matrices. The recoveries of the
pesticides ranged from 60.5 to 128% (RSD <= 19.0%) at the spiked concentration
level of 0.01 (or 0.03) mg/kg and 62.9 to 130% (RSD <= 13.0%) at 0.1 mg/kg.
Compared with the commercial cleanup solid-phase extraction cartridges, the
present adsorbent combination displayed better purification effect and shorter
sample pretreatment time, demonstrating potential application prospect in the
complex matrix sample analysis.
PMID- 28426178
TI - Multiplexing N-glycan analysis by DNA analyzer.
AB - Analysis of N-glycan structures has been gaining attentions over the years due to
their critical importance to biopharma-based applications and growing roles in
biological research. Glycan profiling is also critical to the development of
biosimilar drugs. The detailed characterization of N-glycosylation is mandatory
because it is a nontemplate driven process and that significantly influences
critical properties such as bio-safety and bio-activity. The ability to
comprehensively characterize highly complex mixtures of N-glycans has been
analytically challenging and stimulating because of the difficulties in both the
structure complexity and time-consuming sample pretreatment procedures. CE-LIF is
one of the typical techniques for N-glycan analysis due to its high separation
efficiency. In this paper, a 16-capillary DNA analyzer was coupled with a
magnetic bead glycan purification method to accelerate the sample preparation
procedure and therefore increase N-glycan assay throughput. Routinely, the
labeling dye used for CE-LIF is 8-aminopyrene-1,3,6-trisulfonic acid, while the
typical identification method involves matching migration times with database
entries. Two new fluorescent dyes were used to either cross-validate and increase
the glycan identification precision or simplify sample preparation steps.
Exoglycosidase studies were carried out using neuramididase, galactosidase, and
fucosidase to confirm the results of three dye cross-validation. The optimized
method combines the parallel separation capacity of multiple-capillary separation
with three labeling dyes, magnetic bead assisted preparation, and exoglycosidase
treatment to allow rapid and accurate analysis of N-glycans. These new methods
provided enough useful structural information to permit N-glycan structure
elucidation with only one sample injection.
PMID- 28426179
TI - Novel, Selective, and Developable Dopamine D3 Antagonists with a Modified "Amino"
Region.
AB - This Minireview describes a presentation made at the XXIV National Meeting in
Medicinal Chemistry (NMMC) held in Perugia (Italy), September 11-14, 2016. It
relates to the discovery of novel templates of the so-called "amino" region of
dopamine D3 receptor antagonists. Moving from the early scaffolds, which were
modified in the amine portion, this review discusses the variations that led to
the discovery of new systems published in 2016, which allowed the identification
of compounds endowed with great selectivity over the dopamine D2 receptor and the
human ether-a-go-go-related gene (hERG) ion channel. The main efforts in
characterizing these compounds were devoted not only to determining their potency
and selectivity relative to closely associated targets (e.g., the dopamine D2
receptor), but to ensure a large therapeutic window versus liability points such
as hERG. In particular, we present examples of derivatives with selectivities
greater than 2000-fold. Furthermore, much focus is devoted to the overall
developability of the scaffolds, ensuring that appropriate physicochemical and
pharmacokinetic parameters are present in all compounds progressing through the
screening cascade.
PMID- 28426180
TI - Secondary Sensitivity Control of Silver-Nanowire-Based Resistive-Type Strain
Sensors by Geometric Modulation of the Elastomer Substrate.
AB - A secondary method for modulation of the sensitivity in silver nanowire (AgNW)
resistive-type strain sensors without the need to change the material or coating
process in the sensory layer is demonstrated. Instead of using a planar elastomer
(polydimethylsiloxane is used in this study) substrate, diverse relief structures
are introduced to induce nonuniform and complex strain within the elastic
substrate and thereby different distributions of the crack density of the AgNWs
upon stretching, which plays an important role in the modulation of the gauge
factor (GF). Analysis of the sensory layer and mechanical studies reveal that a
lower height ratio and greater number of trenches enhance the sensor sensitivity,
for example, reaching a GF of 926 at 9.6% in this study. The demonstration of
wrist-motion sensors using the technology illustrates the feasibility of using
relief structures for various types of sensors and sensitivity ranges using an
identical sensor layer.
PMID- 28426181
TI - Prognostic significance of cachexia score assessed by CT in male patients with
small cell lung cancer.
AB - To determine the prognostic significance of CT-determined cachexia scores (CSs)
in 127 consecutive male small cell lung cancer (SCLC) patients, cross-sectional
areas of muscle and fat tissues at the third lumbar vertebra (L3) were
retrospectively measured on baseline CT images. CSs were determined based on the
presence of sarcopenia and/or adipopenia. According to the presence of sarcopenia
(L3 muscle index <55 cm2 /m2 , 86.8%) and adipopenia (L3 fat index <22 cm2 /m2 ,
11.8%), CSs were defined as follows: CS2 (sarcopenia and adipopenia, 11.8%), CS1
(sarcopenia only, 74.8%) and CS0 (13.4%). CS2 was significantly related to lower
body mass index (p < .001) and poor performance status (p = .002), and patients
with CS2 had shorter OS than patients with CS1 or CS0 (median OS, 5.0 months vs.
8.9 months vs. 18.3 months; p = .007). Multivariable analysis revealed that CS
was an independent prognostic factor of poor survival (HR, 1.99 for CS1 and 2.59
for CS2, p = .036 and .023, CS0 as a reference), along with extensive stage (p <
.001), supportive care only (p < .001) and an elevated lactate dehydrogenase (p =
.005). CT-determined CSs, based on the presence of sarcopenia and/or adipopenia,
could be used to predict prognosis in male SCLC.
PMID- 28426182
TI - Usefulness and accuracy of MALDI-TOF mass spectrometry as a supplementary tool to
identify mosquito vector species and to invest in development of international
database.
AB - Arthropod-borne diseases are important causes of morbidity and mortality. The
identification of vector species relies mainly on morphological features and/or
molecular biology tools. The first method requires specific technical skills and
may result in misidentifications, and the second method is time-consuming and
expensive. The aim of the present study is to assess the usefulness and accuracy
of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
(MALDI-TOF MS) as a supplementary tool with which to identify mosquito vector
species and to invest in the creation of an international database. A total of 89
specimens belonging to 10 mosquito species were selected for the extraction of
proteins from legs and for the establishment of a reference database. A blind
test with 123 mosquitoes was performed to validate the MS method. Results showed
that: (a) the spectra obtained in the study with a given species differed from
the spectra of the same species collected in another country, which highlights
the need for an international database; (b) MALDI-TOF MS is an accurate method
for the rapid identification of mosquito species that are referenced in a
database; (c) MALDI-TOF MS allows the separation of groups or complex species,
and (d) laboratory specimens undergo a loss of proteins compared with those
isolated in the field. In conclusion, MALDI-TOF MS is a useful supplementary tool
for mosquito identification and can help inform vector control.
PMID- 28426183
TI - Mass Production of Cell-Laden Calcium Alginate Particles with Centrifugal Force.
AB - This paper describes a centrifuge-based device for oil-free and mass production
of calcium-alginate (Ca-alginate) particles. The device is composed of four
components: a tank with a glass capillary for forming sodium alginate droplets, a
collecting bath with calcium chloride (CaCl2 ) solution, a waste liquid box, and
a bypass channel bridged between the collecting bath and the waste liquid box.
When the device is centrifuged, extra CaCl2 solution in the collecting bath is
delivered to the waste liquid box to maintain the appropriate liquid level of
CaCl2 solution for the production of monodisperse Ca-alginate particles. The
proposed device enables oil-free production of over 45 000 uniformly sized Ca
alginate particles in a single 240 s process, whereas using the conventional
method with only a glass capillary, ~1000 particles are formed within the same
processing time. Because of the high biocompatibility of the oil-free process,
the device is applicable to cell encapsulation in Ca-alginate particles with high
cell viability, as well as the formation of a macroscopic 3D cellular structure
using Ca-alginate particles covered with cells as assembly modules. These results
suggest that the device can be a useful tool for preparing experimental platforms
in biomedical and tissue engineering fields.
PMID- 28426184
TI - Alterations in mandibular morphology associated with glypican 1 and glypican 3
gene mutations.
AB - OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that
act downstream in many of the signalling pathways associated with
craniosynostosis. Morphometric data from GPC-knockout mice were analysed to
determine whether elimination of GPC1 and GPC3 genes would alter mandibular
morphology. SETTING AND SAMPLE POPULATION: The murine model included five male
and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild
type (control) groups. Female GPC3-knockout mice had a very high rate of
perinatal lethality, and therefore, only five males were included in this group.
METHODS: The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5),
GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing
five landmark-based linear dimensions: anterior and posterior lengths, as well as
ascending, descending and posterior heights. Measurements were recorded on three
dimensional micro-CT reconstructions. RESULTS: GPC3-knockout mandibles were
larger than wild-type mandibles for all dimensions (P<.05). Mandibular heights
were more affected than lengths. A decreasing trend of mandibular dimensions
across the mouse groups (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild
type) (P<.05) indicated that an increase in mandibular size was associated with
increased GPC3 expression, but not GPC1. CONCLUSIONS: Alterations in GPC3
expression are likely to mediate changes to mandibular size in craniosynostosis.
These findings have potential future applications in the prevention and treatment
of craniosynostosis and associated craniofacial dysmorphology.
PMID- 28426186
TI - Issue at the Heart of Advancing the De-Adoption of Low-Value Care. Proceedings
from an expert roundtable.
AB - Identifying and paying for value has become a recurrent theme of health care
reforms. Its corollary, reducing the prevalence of, and resources directed to,
ineffective or marginally effective care, has received far less attention. In
July 2016, the University of Pennsylvania's Leonard Davis Institute of Health
Economics (LDI) convened a diverse set of national leaders and stakeholders
representing industry, think-tanks, provider and patient groups, and academic
experts to tackle how health systems, payers, and providers can spur the 'de
adoption' of medical practices and technologies no longer considered
valuable.While the roundtable of experts unanimously supports the need for de
adoption and current efforts to curb the use of low-value practices or
technologies, they identified four specific polarities at the heart of the debate
about how best to build the momentum around deadoption, and move it forward. They
are: 1) value (targeting ineffective, even harmful, care or expanding efforts to
address care of limited value); 2) resource allocation (spending less or
redirecting spending); 3) quality improvement (a subset of QI or a distinct
process); 4) level of intervention (policy, payment, provider, or organization).
In addition to these polarities, several key questions emerged that form
practical next steps for advancing de-adoption activities. With an eye toward
advancing de-adoption, this brief summarizes the polarities and questions that
suggest priorities for a future research agenda and policy-relevant action steps.
PMID- 28426185
TI - Integrated HIV care and service engagement among people living with HIV who use
drugs in a setting with a community-wide treatment as prevention initiative: a
qualitative study in Vancouver, Canada.
AB - INTRODUCTION: Social-structural inequities impede access to, and retention in,
HIV care among structurally vulnerable people living with HIV (PLHIV) who use
drugs. The resulting disparities in HIV-related outcomes among PLHIV who use
drugs pose barriers to the optimization of HIV treatment as prevention (TasP)
initiatives. We undertook this study to examine engagement with, and impacts of,
an integrated HIV care services model tailored to the needs of PLHIV who use
drugs in Vancouver, Canada - a setting with a community-wide TasP initiative.
METHODS: We conducted qualitative interviews with 30 PLHIV who use drugs
recruited from the Dr. Peter Centre, an HIV care facility operating under an
integrated services model and harm reduction approach. We employed novel
analytical techniques to analyse participants' service trajectories within this
facility to understand how this HIV service environment influences access to, and
retention in, HIV care among structurally vulnerable PLHIV who use drugs.
RESULTS: Our findings demonstrate that participants' structural vulnerability
shaped their engagement with the HIV care facility that provided access to
resources that facilitated retention in HIV care and antiretroviral treatment
adherence. Additionally, the integrated service environment helped reduce burdens
associated with living in extreme poverty by meeting participants' subsistence
(e.g. food, shelter) needs. Moreover, access to multiple supports created a
structured environment in which participants could develop routine service use
patterns and have prolonged engagement with supportive care services. Our
findings demonstrate that low-barrier service models can mitigate social and
structural barriers to HIV care and complement TasP initiatives for PLHIV who use
drugs. CONCLUSION: These findings highlight the critical role of integrated
service models in promoting access to health and support services for
structurally vulnerable PLHIV. Complementing structural interventions with
integrated service models that are tailored to the needs of structurally
vulnerable PLHIV who use drugs will be pursuant to the goals of TasP.
PMID- 28426189
TI - Issues Confronting Rural Pharmacies after a Decade of Medicare Part D.
AB - Purpose. The RUPRI Center for Rural Health Policy Analysis has been monitoring
the status of rural independent pharmacies since the implementation of Medicare
Part D in 2005. After a decade of Part D, we reassess in this brief the issues
that concern rural pharmacies and may ultimately challenge their provision of
services. This reassessment is based on survey responses from rural pharmacists.
Key Findings: (1) Rural pharmacists indicated that two challenges--direct and
indirect remuneration (DIR) fees, and delayed maximum allowable cost (MAC)
adjustment--ranked highest on scales of both magnitude and immediacy. Nearly
eighty (79.8) percent of respondents reported DIR fees as a very large magnitude
challenge, with 83.3 percent reporting this as a very immediate challenge.
Seventy-eight percent of respondents reported MACs not being updated quickly
enough to reflect changes in wholesale drug costs as a very large magnitude
challenge, with 79.7 percent indicating it as a very immediate challenge. (2)
Medicare Part D continues to be a concern for rural pharmacies--58.8 percent of
pharmacists said being an out-of-network pharmacy for Part D plans was a very
large magnitude challenge (an additional 29.0 percent said large magnitude) and
60.5 percent said it was a very immediate challenge (an additional 28.1 percent
said moderately immediate). (3) Pharmacy staffing, competition from pharmacy
chains, and contracts for services for Medicaid patients were less likely to be
reported as significant or immediate challenges.
PMID- 28426190
TI - Robust Polymer Electrolyte Membranes with High Ambient-Temperature Lithium-Ion
Conductivity via Polymerization-Induced Microphase Separation.
AB - Mechanically robust polymer electrolyte membranes (PEMs) exhibiting high ionic
conductivity at ambient temperature are a prerequisite for next-generation
electrochemical devices. We utilized a polymerization-induced microphase
separation (PIMS) strategy to prepare nanostructured materials comprising
continuous conducting nanochannels intertwined with a mechanically and thermally
robust cross-linked polymeric framework. Addition of succinonitrile (SN) rendered
the poly(ethylene oxide)/lithium (Li) salt conducting domains completely
amorphous, resulting in outstanding conductivities (~0.35 mS/cm) at 30 degrees
C. Concurrently, a densely cross-linked polystyrene framework provided mechanical
robustness (modulus E' ~ 0.3 GPa at 30 degrees C) to the hybrid material. This
work highlights a facile, single-pot strategy involving a homogeneous liquid
reaction precursor that yields a high-performance ion-conducting membrane
attractive for lithium-battery applications.
PMID- 28426191
TI - Genome-Wide Abolishment of Mobile Genetic Elements Using Genome Shuffling and
CRISPR/Cas-Assisted MAGE Allows the Efficient Stabilization of a Bacterial
Chassis.
AB - The ideal bacterial chassis provides a simplified, stable and predictable host
environment for synthetic biological circuits. Mutability and evolution can,
however, compromise stability, leading to deterioration of artificial genetic
constructs. By eliminating certain sources of instability, these undesired
genetic changes can be mitigated. Specifically, deletion of prophages and
insertion sequences, nonessential constituents of bacterial genomes, has been
shown to be beneficial in cellular and genetic stabilization. Here, we sought to
establish a rapid methodology to improve the stability of microbial hosts. The
novel workflow involves genome shuffling between a mobile genetic element-free
strain and the target cell, and subsequent rounds of CRISPR/Cas-assisted MAGE on
multiplex targets. The power and speed of the procedure was demonstrated on E.
coli BL21(DE3), a host routinely used for plasmid-based heterologous protein
expression. All 9 prophages and 50 insertion elements were efficiently deleted or
inactivated. Together with additional targeted manipulations (e.g., inactivation
of error-prone DNA-polymerases), the changes resulted in an improved bacterial
host with a hybrid (harboring segments of K-12 DNA), 9%-downsized and clean
genome. The combined capacity of phage-mediated generalized transduction and
CRISPR/Cas-selected MAGE offers a way for rapid, large scale editing of bacterial
genomes.
PMID- 28426192
TI - Profiling Cellular Substrates of Lysine Acetyltransferases GCN5 and p300 with
Orthogonal Labeling and Click Chemistry.
AB - p300 and GCN5 are two representative lysine acetyltransferases (KATs) in
mammalian cells. It was recently reported that they possess multiple
acyltransferase activities including acetylation, propionylation, and
butyrylation of the epsilon-amino group of lysine residues of histones and non
histone protein substrates. Although thousands of acetylated substrates and
acetylation sites have been identified by mass spectrometry-based proteomic
screening, our knowledge about the causative connections between individual KAT
members and their corresponding sub-acylomes remain very limited. Herein, we
applied 3-azidopropionyl CoA (3AZ-CoA) as a bioorthogonal surrogate of acetyl-,
propionyl- and butyryl-CoA for KAT substrate identification. We successfully
attached the azide as a chemical warhead to cellular substrates of wild-type p300
and engineered GCN5. The substrates were subsequently labeled with biotin tag
through the copper-catalyzed azide-alkyne cycloaddition (CuAAC). Following
protein enrichment on streptavidin-coated resin, we conducted LC-MS/MS studies
from which more than four hundred proteins were identified as GCN5 or p300
substrate candidates. These proteins are either p300- or GCN5-unique or shared by
the two KATs and are extensively involved in various biological events including
gene expression, cell cycle, and cellular metabolism. We also experimentally
validated two novel substrates of GCN5, that is, IQGAP1 and SMC1. These results
demonstrate extensive engagement of GCN5 and p300 in cellular pathways and
provide new insights into understanding their functions in specific biological
processes.
PMID- 28426193
TI - The Glutathione Conundrum: Stoichiometric Disconnect between Its Formation and
Oxidative Stress.
AB - Glutathione (GSH) is the most abundant antioxidant and is believed to maintain
redox potential in tissues, cells, and individual compartments. However, GSH
concentrations in some tumor cells and tissues have been reported to be as high
as 1-10 mM, a concentration that is up to 10,000-fold higher than that of
reactive oxygen species. Critical quantitative evaluation of glutathione's
proposed functions suggests that glutathione is an amino acid checkpoint. In this
role, glutathione contributes to regulating cell proliferation and apoptosis,
pending amino acid availability.
PMID- 28426194
TI - Development of a Porous Coordination Polymer with a High Gas Capacity Using a
Thiophene-Based Bent Tetracarboxylate Ligand.
AB - A new porous coordination polymer (PCP) based on a ligand with a unique bent
angle bearing a thiophene-bridged bent carboxylate ligand and the Cu2+ ion was
synthesized and structurally characterized. The structure has a pillared-layer
framework based on a kagome-like layer with aromatic partition groups. It
exhibits a high CO2 uptake of 180 mL(STP)/g at 1 bar, and 400 mL(STP)/g at 30 bar
at 273 K. The uptakes of C2H2 and C2H4 reach 164 and 160 mL(STP)/g at 298 K and 1
bar, with good selectivity of C2H2 and C2H4 over CH4, both of which are among the
highest levels of reported PCPs.
PMID- 28426195
TI - One-Step Fabrication of Non-Fluorinated Transparent Super-Repellent Surfaces with
Tunable Wettability Functioning in Both Air and Oil.
AB - In this paper, we have developed a one-step thermal treatment of
polydimethylsiloxane (PDMS) liquid to create transparent super-repellent surface
(TSS) and super-repellent powder. They are super-repellent toward water and
ethylene glycol. During the one-step thermal treatment, PDMS soot is generated
and deposited onto a glass slide (GS) surface to fabricate the TSS without
fluorosilane modification. The facilely obtained TSS presented
superhydrophobicity and self-cleaning property when immersed into very low
surface tension oils such as petroleum ether, hexadecane, peanut oil, and
dodecane. Interestingly, by controlling heating time and temperature, wettability
of the treated GS surface and the remained white powder can be regulated. The
mechanism of tunable wettability was revealed and analyzed by investigating the
variations of surface morphology and chemical composition. More importantly, TSS
was able to repel highly corrosive aqua regia and saturated NaOH solutions. TSS
maintained excellent superhydrophobicity even after chemical and mechanical
damages. This simple thermal deposition method was also applicable for other
thermally stable substrates to achieve super-repellency, which are believed to
find very promising applications.
PMID- 28426196
TI - Chiral Inorganic Nanostructures.
AB - The field of chiral inorganic nanostructures is rapidly expanding. It started
from the observation of strong circular dichroism during the synthesis of
individual nanoparticles (NPs) and their assemblies and expanded to sophisticated
synthetic protocols involving nanostructures from metals, semiconductors,
ceramics, and nanocarbons. Besides the well-established chirality transfer from
bioorganic molecules, other methods to impart handedness to nanoscale matter
specific to inorganic materials were discovered, including three-dimentional
lithography, multiphoton chirality transfer, polarization effects in nanoscale
assemblies, and others. Multiple chiral geometries were observed with
characteristic scales from angstroms to microns. Uniquely high values of chiral
anisotropy factors that spurred the development of the field and differentiate it
from chiral structures studied before, are now well understood; they originate
from strong resonances of incident electromagnetic waves with plasmonic and
excitonic states typical for metals and semiconductors. At the same time,
distinct similarities with chiral supramolecular and biological systems also
emerged. They can be seen in the synthesis and separation methods, chemical
properties of individual NPs, geometries of the nanoparticle assemblies, and
interactions with biological membranes. Their analysis can help us understand in
greater depth the role of chiral asymmetry in nature inclusive of both earth and
space. Consideration of both differences and similarities between chiral
inorganic, organic, and biological nanostructures will also accelerate the
development of technologies based on chiroplasmonic and chiroexcitonic effects.
This review will cover both experiment and theory of chiral nanostructures
starting with the origin and multiple components of mirror asymmetry of
individual NPs and their assemblies. We shall consider four different types of
chirality in nanostructures and related physical, chemical, and biological
effects. Synthetic methods for chiral inorganic nanostructures are systematized
according to chirality types, materials, and scales. We also assess technological
prospects of chiral inorganic materials with current front runners being
biosensing, chiral catalysis, and chiral photonics. Prospective venues for future
fundamental research are discussed in the conclusion of this review.
PMID- 28426197
TI - Photoluminescence Segmentation within Individual Hexagonal Monolayer Tungsten
Disulfide Domains Grown by Chemical Vapor Deposition.
AB - We show that hexagonal domains of monolayer tungsten disulfide (WS2) grown by
chemical vapor deposition (CVD) with powder precursors can have discrete
segmentation in their photoluminescence (PL) emission intensity, forming
symmetric patterns with alternating bright and dark regions. Two-dimensional maps
of the PL reveal significant reduction within the segments associated with the
longest sides of the hexagonal domains. Analysis of the PL spectra shows
differences in the exciton to trion ratio, indicating variations in the exciton
recombination dynamics. Monolayers of WS2 hexagonal islands transferred to new
substrates still exhibit this PL segmentation, ruling out local strain in the
regions as the dominant cause. High-power laser irradiation causes preferential
degradation of the bright segments by sulfur removal, indicating the presence of
a more defective region that is higher in oxidative reactivity. Atomic force
microscopy (AFM) images of topography and amplitude modes show uniform thickness
of the WS2 domains and no signs of segmentation. However, AFM phase maps do show
the same segmentation of the domain as the PL maps and indicate that it is caused
by some kind of structural difference that we could not clearly identify. These
results provide important insights into the spatially varying properties of these
CVD-grown transition metal dichalcogenide materials, which may be important for
their effective implementation in fast photo sensors and optical switches.
PMID- 28426198
TI - Unified Biosynthetic Origin of the Benzodipyrrole Subunits in CC-1065.
AB - CC-1065 is the first characterized member of a family of naturally occurring
antibiotics including yatakemycin and duocarmycins with exceptionally potent
antitumor activity. CC-1065 contains three benzodipyrroles (1a-, 1b-, and 1c-) of
which the 1a-subunit is remarkable by being composed of a cyclopropane ring, and
the mechanism for the biological formation of benzodipyrrole rings remains
elusive. Previously, biosynthetic studies of CC-1065 were limited to
radioactively labeled precursor feeding experiments, which showed that tyrosine
(Tyr) and serine (Ser) were incorporated into the two benzodipyrrole (1b- and 1c
) subunits via the same mode but that this was different from the key
cyclopropabenzodipyrrole (1a-) subunit with N1-C2-C3 derived from Ser. Herein,
the biosynthetic gene cluster of CC-1065 has been cloned, analyzed, and
characterized by a series of gene inactivations. Significantly, a key
intermediate bearing a C7-OH group derived from a Deltac10C mutant exhibited
improved cytotoxicity. Moreover, this data inspired us to suspect that the 1a
subunit might employ the same precursor incorporation mode as the 1b- and 1c
subunits. Subsequently, 13C-labeled Tyr feeding experiments confirmed that the N1
C2-C3 is originated from Tyr via DOPA as an intermediate. Collectively, a
biosynthetic pathway of benzodipyrrole is proposed featuring a revised and
unified precursor incorporation mode, which implicates an oxidative cyclization
strategy for the assembly of benzodipyrrole. This work sets the stage for further
study of enzymatic mechanisms and combinatorial biosynthesis for new DNA
alkylating analogues.
PMID- 28426199
TI - Sequestering Soil Organic Carbon: A Nitrogen Dilemma.
PMID- 28426200
TI - Facile Design and Fabrication of Superwetting Surfaces with Excellent Wear
Resistance.
AB - Preparation of mechanically durable superwetting surfaces is imperative, yet
challenging for the wide range of real applications where high durability is
required. Mechanical wear on superwetting surfaces usually degrades weak
roughness, leading to loss of functions. In this study, wear-resistant
superhydrophilic/underwater superoleophobic and superhydrophobic surfaces are
prepared by anchoring reinforced coatings via adhesive-swelling and adhesive
bonding processes, respectively. The results of the sandpaper abrasion (grit no.
600, 24 kPa) show that superhydrophilic nylon/SiO2 coatings and superhydrophobic
polyurethane/TiO2 coatings retain their functions after suffering the abrasion
distances of 70 cm and more than 1000 cm, respectively. Reinforced coatings
formed by consecutive roughness and improved adhesion between coatings and
substrates are responsible for repeatedly generated superwettability after
exposure to mechanical stresses and demonstrated to be feasible for designing
wear-resistant superwetting surfaces. Furthermore, this novel architecture of
"reinforced coating with consecutive roughness + high adhesion" may demand
desired coating materials and reliable coating-fixing techniques for sustaining
sufficient roughness and is superior to currently existing technologies in
advancing wear-resistance of superwetting surfaces.
PMID- 28426201
TI - Exploiting Solvate Ionic Liquids for Amine Gas Analysis on a Quartz Crystal
Microbalance.
AB - We demonstrated in this work the usefulness of solvate ionic liquids SIL 3 and
SIL 4 for chemoselective detection of amine gases on a quartz crystal
microbalance. This detection of gaseous amines was achieved by nucleophilic
aromatic addition reactions with super electrophilic SIL 3 or SIL 4 thin-coated
on quartz chips. Starting with inexpensive reagents, functional SIL 3 and SIL 4
could be readily synthesized in two short steps with high isolated yield (81 and
77%, respectively). The QCM platform developed in this work is readily applicable
and highly sensitive to low molecular weight amine gases: for propylamine gas at
10 Hz decrease in resonance frequency, the sensitivity of detection using SIL 4
was 5.4 ppb. This simple and convenient assembly of neutral ligands (e.g., 1a and
1b) with Li+ ion to afford room temperature ionic liquids should be of great
importance for a myriad of applications. To the best of our knowledge, no example
to date of reports based on nucleophilic aromatic addition reactions
demonstrating sensitive amine gas detection in solvate ionic liquids on a QCM has
been reported. Furthermore, because of the high color intensity of the
Meisenheimer complexes formed, our preliminary result showed that SIL 4 loaded on
copier paper can be used not only as a portable amine gas sensor but also as a
potential invisible ink that is only revealed by amine vapor.
PMID- 28426202
TI - Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating
Tumor Hypoxia.
AB - Hypoxia development in tumor is closely associated with its increased
aggressiveness and strong resistance to therapy, leading to the poor prognosis in
several cancer types. Clinically, invasive oxygen microelectrode and high dosage
radiotherapy are often utilized to accurately detect and effectively fight
hypoxia. Recently, however, there has been a surge of interdisciplinary research
aiming at developing functional molecules and nanomaterials that can be used to
noninvasively image and efficiently treat hypoxic tumors. In this review, we will
provide an overview of the reports published to date on the imaging and therapy
of hypoxic tumors. First, we will present the design concepts and engineering of
various hypoxia-responsive probes that can be applied to image hypoxia
noninvasively, in an order of fluorescent imaging, positron emission tomography,
magnetic resonance imaging, and photoacoustic imaging. Then, we will summarize
the up-to-date functional nanomaterials which can be used for the effective
treatments of tumor hypoxia. The well-established chemical functions of these
elaborately designed nanostructures will enable clinicians to adopt specific
treatment concepts by overcoming or even utilizing hypoxia. Finally, challenges
and future perspectives facing the researchers in the field will be discussed.
PMID- 28426203
TI - Tyrosine Kinase Activation and Conformational Flexibility: Lessons from Src
Family Tyrosine Kinases.
AB - Protein kinases are enzymes that catalyze the covalent transfer of the gamma
phosphate of an adenosine triphosphate (ATP) molecule onto a tyrosine, serine,
threonine, or histidine residue in the substrate and thus send a chemical signal
to networks of downstream proteins. They are important cellular signaling enzymes
that regulate cell growth, proliferation, metabolism, differentiation, and
migration. Unregulated protein kinase activity is often associated with a wide
range of diseases, therefore making protein kinases major therapeutic targets. A
prototypical system of central interest to understand the regulation of kinase
activity is provided by tyrosine kinase c-Src, which belongs to the family of Src
related non-receptor tyrosine kinases (SFKs). Although the broad picture of
autoinhibition via the regulatory domains and via the phosphorylation of the C
terminal tail is well characterized from a structural point of view, a detailed
mechanistic understanding at the atomic-level is lacking. Advanced computational
methods based on all-atom molecular dynamics (MD) simulations are employed to
advance our understanding of tyrosine kinase activation. The computational
studies suggest that the isolated kinase domain (KD) is energetically most
favorable in the inactive conformation when the activation loop (A-loop) of the
KD is not phosphorylated. The KD makes transient visits to a catalytically
competent active-like conformation. The process of bimolecular trans
autophosphorylation of the A-loop eventually locks the KD in the active state.
Activating point mutations may act by slightly increasing the population of the
active-like conformation, enhancing the availability of the A-loop to be
phosphorylated. The Src-homology 2 (SH2) and Src-homology 3 (SH3) regulatory
domains, depending upon their configuration, either promote the inactive or the
active state of the kinase domain. In addition to the roles played by the SH3,
SH2, and KD, the Src-homology 4-Unique domain (SH4-U) region also serves as a key
moderator of substrate specificity and kinase function. Thus, a fundamental
understanding of the conformational propensity of the SH4-U region and how this
affects the association to the membrane surface are likely to lead to the
discovery of new intermediate states and alternate strategies for inhibition of
kinase activity for drug discovery. The existence of a multitude of KD
conformations poses a great challenge aimed at the design of specific inhibitors.
One promising computational strategy to explore the conformational flexibility of
the KD is to construct Markov state models from aggregated MD data.
PMID- 28426204
TI - Parameter Optimization for Interaction between C-Terminal Domains of HIV-1 Capsid
Protein.
AB - HIV-1 capsid proteins (CAs) assemble into a capsid that encloses the viral RNA.
The binding between a pair of C-terminal domains (CTDs) constitutes a major
interface in both the CA dimers and the large CA assemblies. Here, we attempt to
use a general residue-level coarse-grained model to describe the interaction
between two isolated CTDs in Monte Carlo simulations. With the standard
parameters that depend only on the residue types, the model predicts a much
weaker binding in comparison to the experiments. Detailed analysis reveals that
some Lennard-Jones parameters are not compatible with the experimental CTD dimer
structure, thus resulting in an unfavorable interaction energy. To improve the
model for the CTD binding, we introduce ad hoc modifications to a small number of
Lennard-Jones parameters for some specific pairs of residues at the binding
interface. Through a series of extensive Monte Carlo simulations, we identify the
optimal parameters for the CTD-CTD interactions. With the refined model
parameters, both the binding affinity (with a dissociation constant of 13 +/- 2
MUM) and the binding mode are in good agreement with the experimental data. This
study demonstrates that the general interaction model based on the Lennard-Jones
potential, with some modest adjustment of the parameters for key residues, could
correctly reproduce the reversible protein binding, thus potentially applicable
for simulating the thermodynamics of the CA assemblies.
PMID- 28426205
TI - Euro 6 Unregulated Pollutant Characterization and Statistical Analysis of After
Treatment Device and Driving-Condition Impact on Recent Passenger-Car Emissions.
AB - This study aims to measure and analyze unregulated compound emissions for two
Euro 6 diesel and gasoline vehicles. The vehicles were tested on a chassis
dynamometer under various driving cycles: Artemis driving cycles (urban, road,
and motorway), the New European Driving Cycle (NEDC) and the World Harmonized
Light-Duty Test Cycle (WLTC) for Europe, and world approval cycles. The emissions
of unregulated compounds (such as total particle number (PN) (over 5.6 nm); black
carbon (BC); NO2; benzene, toluene, ethylbenzene, and xylene (BTEX); carbonyl
compounds; and polycyclic aromatic hydrocarbons (PAHs)) were measured with
several online devices, and different samples were collected using cartridges and
quartz filters. Furthermore, a preliminary statistical analysis was performed on
eight Euro 4-6 diesel and gasoline vehicles to study the impacts of driving
conditions and after-treatment and engine technologies on emissions of regulated
and unregulated pollutants. The results indicate that urban conditions with cold
starts induce high emissions of BTEX and carbonyl compounds. Motorway conditions
are characterized by high emissions of particle numbers and CO, which mainly
induced by gasoline vehicles. Compared with gasoline vehicles, diesel vehicles
equipped with catalyzed or additive DPF emit fewer particles but more NOx and
carbonyl compounds.
PMID- 28426206
TI - Resonance Energies and Lifetimes from the Analytic Continuation of the Coupling
Constant Method: Robust Algorithms and a Critical Analysis.
AB - The energy of a metastable state can be computed by adding an artificial
stabilizing potential to the Hamiltonian, increasing the stabilization until the
metastable state is turned into a bound one, and then further increasing the
stabilization until enough bound-state data have been collected so that these can
be extrapolated back to vanishing stabilization. The lifetime of the metastable
state can be obtained from the same data, but only if the extrapolation is
performed by analytic continuation. This extrapolation method is called analytic
continuation of the coupling constant (ACCC). Here we introduce preconditioning
schemes for two of the three established extrapolation algorithms and critically
compare results from all three extrapolation schemes in a variety of situations:
As examples for resonance states serve the pi* temporary anions of ethylene and
formaldehyde as well as a model potential, which provides a case where input data
with full numeric precision are available. In the data collection step, three
different stabilizing potentials are employed, a Coulomb potential, a short-range
Coulomb potential, and a soft-box Voronoi potential. Effects of different orders
of the extrapolating Pade approximant are investigated, and last, the energy
range of input data for the extrapolation is studied. Moreover, all ACCC results
are compared to resonance parameters that have been independently obtained with
the same theoretical method, but with a different continuum approach-complex
scaling for the model and complex absorbing potentials for the temporary anions.
PMID- 28426207
TI - Fe3O4/FeNi Embedded Nanostructure and Its Kinetic Law for Selective Catalytic
Reduction of p-Nitrophenyl Compounds.
AB - To meet the requirement of high catalytic efficiency toward the reduction of p
nitrophenyl compounds, we designed a new one-dimensional Fe3O4/FeNi embedded
nanostructured catalyst synthesized by a one-pot controlling-growth-reduction
process in a solvothermal system, in which Fe3O4 phase was implanted in the base
of FeNi alloy. In the Fe3O4/FeNi catalyst system, the Fe3O4 embedded phase
attracts the nitro group of p-nitrophenyl compounds by its high-density
electrons, which can efficiently promote the activity of amorphous FeNi active
centers for selective catalysis toward the reduction of a range of p-nitrophenyl
compounds. Moreover, for the para-group in the nitrophenyl compounds, an
increasing electron-donating power contributes to a higher catalytic activity,
while electron-withdrawing power obtains the reverse case. Additionally, the
Fe3O4/FeNi composite nanocatalyst exhibited an outstanding cycling performance
over 20 times without obvious performance decay. This work opens an avenue to
design more powerful non-noble metal catalysts for green chemistry.
PMID- 28426208
TI - Global and Local Partitioning of the Charge Transferred in the Parr-Pearson
Model.
AB - Through a simple proposal, the charge transfer obtained from the cornerstone
theory of Parr and Pearson is partitioned, for each reactant, in two channels: an
electrophilic, through which the species accepts electrons, and the other, a
nucleophilic, where the species donates electrons. It is shown that this global
model allows us to determine unambiguously the charge-transfer mechanism
prevailing in a given reaction. The partitioning is extended to include local
effects through the Fukui functions of the reactants. This local model is applied
to several emblematic reactions in organic and inorganic chemistry, and we show
that besides improving the correlations obtained with the global model it
provides valuable information concerning the atoms in the reactants playing the
most important roles in the reaction and thus improving our understanding of the
reaction under study.
PMID- 28426209
TI - Channel-Assisted Proton Conduction Behavior in Hydroxyl-Rich Lanthanide-Based
Magnetic Metal-Organic Frameworks.
AB - Two new lanthanide-based 3D metal-organic frameworks (MOFs),
{[Ln(L)(Ox)(H2O)]n.xH2O} [Ln = Gd3+ and x = 3 (1) and Dy3+ and x = 1.5 (2); H2L =
mucic acid; OxH2 = oxalic acid] showing interesting magnetic properties and
channel-mediated proton conduction behavior, are presented here. Single-crystal X
ray structure analysis shows that, in complex 1, the overall structure originates
from the mucate-bridged gadolinium-based rectangular metallocycles. The packing
view reveals the presence the two types of hydrophilic 1D channels filled with
lattice water molecules, which are strongly hydrogen-bonded with coordinated
water along the a and b axes, whereas for complex 2, the 3D framework originates
from a carboxylate-bridged dysprosium-based criss-cross-type secondary building
block. Magnetic studies reveal that 1 exhibits a significant magnetic entropy
change (-DeltaSM) of 30.6 J kg-1 K-1 for DeltaH= 7 T at 3 K. Our electronic
structure calculations under the framework of density functional theory reveal
that exchange interactions between Gd3+ ions are weak and of the
antiferromagnetic type. Complex 2 shows field-induced single-molecule-magnetic
behavior. Impedance analysis shows that the proton conductivity of both complexes
reaches up to the maximum value of 4.7 * 10-4 S cm-1 for 1 and 9.06 * 10-5 S cm-1
for 2 at high temperature (>75 degrees C) and relative humidity (RH; 95%). The
Monte Carlo simulations confirm the exact location of the adsorbed water
molecules in the framework after humidification (RH = 95%) for 1. Further, the
results from computational simulation also reveal that the presence of a more
dense arrangement of adsorbed water molecules through hydrogen bonding in a
particular type of channel (along the a axis) contributes more to the proton
migration compared to the other channel (along the b axis) in the framework.
PMID- 28426210
TI - Tellurium Distribution and Speciation in Contaminated Soils from Abandoned Mine
Tailings: Comparison with Selenium.
AB - The distribution and chemical species of tellurium (Te) in contaminated soil were
determined by a combination of microfocused X-ray fluorescence (MU-XRF), X-ray
diffraction (MU-XRD), and X-ray absorption fine structure (MU-XAFS) techniques.
Results showed that Te was present as a mixture of Te(VI) and Te(IV) species,
while selenium (Se) was predominantly present in the form of Se(IV) in the soil
contaminated by abandoned mine tailings. In the contaminated soil, Fe(III)
hydroxides were the host phases for Se(IV), Te(IV), and Te(VI), but Te(IV) could
be also retained by illite. The difference in speciation and solubility of Se and
Te in soil can result from different structures of surface complexes for Se and
Te onto Fe(III) hydroxides. Furthermore, our results suggest that the retention
of Te(IV) in soil could be relatively weaker than that of Te(VI) due to
structural incorporation of Te(VI) into Fe(III) hydroxides. These findings are of
geochemical and environmental significance for better understanding the
solubility, mobility, and bioavailability of Te in the surface environment. To
the best of our knowledge, this is the first study reporting the speciation and
host phases of Te in field soil by the MU-XRF-XRD-XAFS techniques.
PMID- 28426211
TI - Dry Particulate Nitrate Deposition in China.
AB - A limited number of ground measurements of dry particulate nitrate deposition
(NO3-) makes it difficult and challenging to fully know the status of the spatial
and temporal variations of dry NO3- depositions over China. This study tries to
expand the ground measurements of NO3- concentrations at monitoring sites to a
national scale, based on the Ozone Monitoring Instrument (OMI) NO2 columns, NO2
profiles from an atmospheric chemistry transport model (Model for Ozone and
Related chemical Tracers, version 4, MOZART-4) and monitor-based sources, and
then estimates the NO3- depositions on a regional scale based on an inferred
model. The ground NO2 concentrations were first derived from NO2 columns and the
NO2 profiles, and then the ground NO3- concentrations were derived from the
ground NO2 concentrations and the relationship between NO2 and NO3- based on
Chinese Nationwide Nitrogen Deposition Monitoring Network (NNDMN). This estimated
dry NO3- depositions over China will be helpful in determining the magnitude and
pollution status in regions without ground measurements, supporting the
construction plan of environmental monitoring in future.
PMID- 28426212
TI - Construction of beta-Trifluoromethyl Enol Ether via Base-Promoted C-O Coupling
and Rearrangement of Hydrogen Atom.
AB - A novel, high-efficiency and high-selectivity construction of beta
trifluoromethyl enol ether via base-induced/promoted C-O coupling of
trifluoromethylated vinyl chloride and phenols is presented with a broad
substrate scope. The reaction mechanism, especially the significantly high
selectivity, was excavated and understood via DFT calculation and is well
supported by the experimental observation.
PMID- 28426213
TI - Role of Mediator and Effects of Temperature on ortho-C-N Bond Fusion Reactions of
Aniline Using Ruthenium Templates: Isolation and Characterization of New
Ruthenium Complexes of the in-Situ-Generated Ligands.
AB - In this work, ortho-C-N bond fusion reactions of aniline are followed by the use
of two different ruthenium mediators. Reaction of aniline with [RuIII(terpy)Cl3]
(terpy = 2,2':6',2"-terpyridine) resulted in a trans bis-aniline ruthenium(II)
complex [1]+ which upon oxidation with H2O2 produced compound [2]+ of a bidentate
ligand, N-phenyl-1,2-benzoquinonediimine, due to an oxidative ortho-C-N bond
fusion reaction. Complex [1]+ and aniline (neat) at 185 degrees C produced a bis
chelated ruthenium complex (3). A previously reported complex [RuII(N-phenyl-1,2
benzoquinonediimine)(aniline)2(Cl)2] (5) undergoes similar oxidation by air at
185 degrees C to produce complex [3]. A separate chemical reaction between
aniline and strongly oxidizing tetra-n-propylammonium perruthenate [(n
pr)4N]+[RuO4]- in air produced a ruthenium complex [4] of a N4
tetraamidophenylmacrocycle ligand via multiple ortho-C-N bond fusion reaction.
Notably, the yield of this product is low (5%) at 100 degrees C but increases to
25% in refluxing aniline. All these complexes are characterized fully by their
physicochemical characterizations and X-ray structure determination. From their
structural parameters and other spectroscopic studies, complex [2]+ is assigned
as [RuII(terpy)(N-phenyl-1,2-benzoquinonediimine)(Cl)]+ whereas complex [4] is
described as a ruthenium(VI) complex comprised of a reduced deprotonated N-phenyl
1,2-diamidobenzene and N4-tetraamidophenylmacrocyclic ligand. Complex [2]+
exhibits one reversible oxidation at 1.32 V and one reversible reduction at -0.75
V vs Ag/AgCl reference electrode. EPR of the electrogenerated complexes has
revealed that the oxidized complex is a ruthenium(III) complex with an axial EPR
spectrum at gav= 2.06. The reduced complex [2], on the other hand, shows a single
line EPR signal at gav= 1.998. In contrast, complex [4] shows two successive one
electron oxidation waves at 0.5 and 0.8 V and an irreversible reduction wave at
0.9 V. EPR studies of the oxidized complexes [4]+ and [4]2+ reveal that
oxidations are ligand centered. DFT calculations were employed to elucidate the
electronic structures as well as the redox processes associated with the above
complexes. Aerial ortho-C-N bond fusion reactions of aniline using two different
mediators, viz. [RuIII(terpy)Cl3] and [(n-pr)4N]+[RuO4]-, have been followed. It
is found that in the case of oxidizable Ru(III) mediator complex, C-N bond fusion
is limited only to dimerization reaction whereas the high-valent Ru(VII) salt
mediates multiple C-N bond fusion reactions leading to the formation of a novel
tetradentate N4-tetraamidophenylmacrocyclic ligand. Valence ambiguity in the
complexes of the resultant redox-active ligands is scrutinized.
PMID- 28426214
TI - Calix[5]arene Through-the-Annulus Threading of Dialkylammonium Guests Weakly
Paired to the TFPB Anion.
AB - Through-the-annulus threading of calix[5]arene penta-O-ethers by dialkylammonium
cations coupled to the loosely coordinating superweak TFPB- anion has been
achieved. 1H NMR titration data show that preorganization of the calix[5]arene
scaffold leads to great thermodynamic stability of the pseudorotaxane complexes
as well as to a favorable threading kinetic. Thus, calix[5]arene 1c, bearing tert
butyl groups at the wide rim, was threaded by all of the cations under study
(with the exception of the dibenzylammonium 2b+) more tightly than the other
derivatives under investigation (Ka's up to 2.02 +/- 0.2 * 105 M-1) because of
its preorganized cone conformation. According to DFT calculations, van der Waals
interactions between the tert-butyl groups of 1c and the alkyl chain of the
cationic axle are likely responsible for the remarkable stability observed. The
threading of the calix[5]arene wheels with the asymmetric pentylbenzylammonium
axle 2c+ led to the toposelective formation of the endo-pentylpseudorotaxane
stereoisomer in agreement with the known "endo-alkyl rule". Owing to the steric
hindrance of the axle phenyl group, the threading of the guest was seen to occur
in a unidirectional fashion through the calixarene narrow rim.
PMID- 28426215
TI - Five- and Six-Coordinated Silver(I) Complexes Derived from 2,6
(Pyridyl)iminodiadamantanes: Sustained Release of Bioactive Silver toward
Bacterial Eradication.
AB - Silver(I) complexes of two designed tridentate ligands, namely, 2,6
(pyridyl)iminoditriazaadamantane (pydTAm) and 2,6-(pyridyl)iminodiadamantane
(pydAm), have been synthesized and structurally characterized.
[Ag(pydTAm)2](CF3SO3) (1), the hitherto unknown mer isomer of a silver(I)
octahedral complex, crystallizes in a highly symmetric body-centered cubic I43m
space group. Quite in contrast, the AgI center in the analogous
[Ag(pydAm)2](CF3SO3) (2) complex resides in a trigonal-bipyramidal geometry and
crystallizes in a triclinic P1 space group with two crystallographically
independent molecules in the asymmetric unit. Complex 1 exhibits exceptional
solubility in aqueous media and leads to the efficient eradication of several
bacterial strains upon sustained release of bioactive silver.
PMID- 28426216
TI - Total Syntheses of Highly Oxidized ent-Kaurenoids Pharicin A, Pharicinin B, 7-O
Acetylpseurata C, and Pseurata C: A [5+2] Cascade Approach.
AB - The unprecedented oxidative dearomatization-induced [5+2] cycloaddition/pinacol
type 1,2-acyl migration cascade efficiently generates a quaternary carbon center
and assembles the highly oxygenated bicyclo[3.2.1]octane framework of ent-kaurene
diterpenoids. By incorporation of the subsequent retro-aldol/aldol process and
singlet oxygen ene reaction, this concise and convergent approach has enabled the
first asymmetric total syntheses of pharicin A, pharicinin B, 7-O-acetylpseurata
C, and pseurata C.
PMID- 28426217
TI - Phosphorus Depletion as a Green Alternative to Biocides for Controlling
Biodegradation of Metalworking Fluids.
AB - Metalworking fluids (MWFs) are used as lubricants and coolants in the
manufacturing operations. Their biodeterioration, while in operation, is a
widespread problem leading to poor performance and worker health issues. Adding
biocides, though effective in reducing microbial growth, leads to the production
of more recalcitrant wastewaters that are difficult to dispose or recycle on
site. Increasing environmental concerns have led to robust legislation for
reducing/eliminating the use of toxic biocides in MWFs, stimulating a growing
interest in the development/application of alternative biological preservation
strategies. In this study, inducing nutrient imbalance was investigated for
controlling microbial growth in MWFs. Phosphorus was immobilized employing
insoluble La2O3 to form LaPO4. Concentrations of La2O3 greater than 0.08%w (%w =
weight percent) completely inhibited microbial growth (from 1.4 * 107 to 0
CFU/mL) and hindered biodegradation. Raman spectroscopy suggested that La2O3
converted intracellular phosphorus into LaPO4. The growth inhibition potentials
of both 0.06%w La(NO3)3 and La2O3 were found to be superior to formaldehyde. The
antimicrobial property of La2O3 (i.e., inhibition) was tenable by adding
sufficient phosphate, acting as an on/off switch for controlling microbial growth
in MWFs. This technology offers the potential to reduce/eliminate the use of
biocides in MWFs, improves the feasibility of end-of-life biological treatment,
and closes the water loop.
PMID- 28426218
TI - The Excited-State Triple Proton Transfer Reaction of 2,6-Diazaindoles and 2,6
Diazatryptophan in Aqueous Solution.
AB - 3-Me-2,6-diazaindole ((2,6-aza)Ind) was strategically designed and synthesized to
probe water molecule catalyzed excited-state proton transfer in aqueous solution.
Upon electronic excitation (lambdamax ~ 300 nm), (2,6-aza)Ind undergoes N(1)-H to
N(6) long-distance proton transfer in neutral H2O, resulting in normal (340 nm)
and proton-transfer tautomer (480 nm) emissions with an overall quantum yield of
0.25. The rate of the water-catalyzed proton transfer shows a prominent H/D
kinetic isotope effect, which is determined to be 8.3 * 108 s-1 and 4.7 * 108 s-1
in H2O and D2O, respectively. Proton inventory experiments indicate the
involvement of two water molecules and three protons, which undergo a relay type
of excited-state triple proton transfer (ESTPT) in a concerted, asynchronous
manner. The results demonstrate for the first time the fundamental of triple
proton transfer in pure water for azaindoles as well as pave a new avenue for 2,6
diazatryptophan, an analogue of tryptophan exhibiting a similar ESTPT property
with (2,6-aza)Ind, to probe biowaters in proteins.
PMID- 28426219
TI - Solution-Processed Cesium Hexabromopalladate(IV), Cs2PdBr6, for Optoelectronic
Applications.
AB - Lead halide perovskites are materials with excellent optoelectronic and
photovoltaic properties. However, some hurdles remain prior to commercialization
of these materials, such as chemical stability, phase stability, sensitivity to
moisture, and potential issues due to the toxicity of lead. Here, we report a new
type of lead-free perovskite related compound, Cs2PdBr6. This compound is
solution processable, exhibits long-lived photoluminescence, and an optical band
gap of 1.6 eV. Density functional theory calculations indicate that this compound
has dispersive electronic bands, with electron and hole effective masses of 0.53
and 0.85 me, respectively. In addition, Cs2PdBr6 is resistant to water, in
contrast to lead-halide perovskites, indicating excellent prospects for long-term
stability. These combined properties demonstrate that Cs2PdBr6 is a promising
novel compound for optoelectronic applications.
PMID- 28426220
TI - Fluorescent Neuraminidase Assay Based on Supramolecular Dye Capture After
Enzymatic Cleavage.
AB - A conceptually new type of enzymatic cleavage assay is reported that utilizes in
situ supramolecular capture of the fluorescent product. A squaraine-derived
substrate with large blocking groups at each end of its structure cannot be
threaded by a tetralactam macrocycle until the blocking groups are removed by
enzyme cleavage. A prototype design responds to viral neuraminidase, an indicator
of influenza infection, and also measures susceptibility of the sample to
neuraminidase inhibitor drugs. The substrate structure incorporates three key
features: (a) a bis(4-amino-3-hydroxyphenyl)squaraine core with bright deep-red
fluorescence and excellent photostability, (b) an N-methyl group at each end of
the squaraine core that ensures fast macrocycle threading kinetics, and (c)
sialic acid blocking groups that prevent macrocycle threading until they are
removed by viral neuraminidase. The enzyme assay can be conducted in aqueous
solution where dramatic colorimetric and fluorescence changes are easily observed
by the naked eye. Alternatively, affinity capture beads coated with macrocycle
can be used to immobilize the liberated squaraine and enable a range of
heterogeneous analysis options. With further optimization, this new type of
neuraminidase assay may be useful in a point of care clinic to rapidly diagnose
influenza infection and also determine which of the approved antiviral inhibitor
drugs is likely to be the most effective treatment for an individual patient. The
assay design is generalizable and can be readily modified to monitor virtually
any type of enzyme-catalyzed cleavage reaction.
PMID- 28426221
TI - Charge Transport in Nanostructured Materials: Implementation and Verification of
Constrained Density Functional Theory.
AB - The in silico design of novel complex materials for energy conversion requires
accurate, ab initio simulation of charge transport. In this work, we present an
implementation of constrained density functional theory (CDFT) for the
calculation of parameters for charge transport in the hopping regime. We verify
our implementation against literature results for molecular systems, and we
discuss the dependence of results on numerical parameters and the choice of
localization potentials. In addition, we compare CDFT results with those of other
commonly used methods for simulating charge transport between nanoscale building
blocks. We show that some of these methods give unphysical results for thermally
disordered configurations, while CDFT proves to be a viable and robust approach.
PMID- 28426222
TI - Structural and Dynamical Properties of Tetraalkylammonium Bromide Aqueous
Solutions: A Molecular Dynamics Simulation Study Using a Polarizable Force Field.
AB - Understanding the behavior of aqueous solutions containing tetraalkylammonium
(TAA) cations is of great significance in a number of applications, including
polymer membranes for fuel cells. In this work, a polarizable force field has
been used to perform atomistic molecular dynamics (MD) simulations of aqueous
solutions containing tetramethylammonium (TMA) or tetrabutylammonium (TBA)
cations and Br counterions. Extensive MD simulations of TMA-Br/water and TBA
Br/water systems were conducted as a function of solution composition (ion
pair:water molar ratios of 1:10, 1:20, 1:30, 1:63, and 1:500) at atmospheric
pressure and 298 K. Our simulations demonstrate excellent agreement with
available experimental data for solution densities and diffusion coefficients of
different species as a function of solution composition, providing us confidence
in analyzed structural and dynamic correlations. Various ion-ion and ion-water
spatial distributions and the extent of cation aggregation are discussed in light
of changes in the structure of cations hydration shells. The delicate balance
between cation ionic core interactions with water and the hydrophobic
interactions of alkyl tails leads to nontrivial self-assembly of TAA cations and
the formation of an interpenetrating cationic network at higher concentrations.
The ions and water dynamics are strongly coupled with the observed structural
correlations and are analyzed in terms of various residence time, diffusion
coefficients, and ionic conductivity.
PMID- 28426223
TI - Over-Destabilization of Protein-Protein Interaction in Generalized Born Model and
Utility of Energy Density Integration Cutoff.
AB - The generalize Born (GB) model is frequently used in MD simulations of
biomolecular systems in aqueous solution. The GB model is usually based on the so
called Coulomb field approximation (CFA) for the energy density integration. In
this study, we report that the GB model with CFA overdestabilizes the long-range
electrostatic attraction between oppositely charged molecules (ionic bond forming
two-helix system and kinesin-tubulin system) when the energy density integration
cutoff, rmax, which is used to calculate the Born energy, is set to a large
value. We show that employing large rmax, which is usually expected to make
simulation results more accurate, worsens the accuracy so that the attraction is
changed into repulsion. It is demonstrated that the overdestabilization is caused
by the overestimation of the desolvation penalty upon binding that originates
from CFA. We point out that the overdestabilization can be corrected by employing
a relatively small cutoff (rmax = 10-15 A), affirming that the GB models, even
with CFA, can be used as a powerful tool to theoretically study the protein
protein interaction, particularly on its dynamical aspect, such as binding and
unbinding.
PMID- 28426225
TI - Quantum Design of pi-Electron Ring Currents in Polycyclic Aromatic Hydrocarbons:
Parallel and Antiparallel Ring Currents in Naphthalene.
AB - Control of pi-electrons in polycyclic aromatic hydrocarbons (PAHs) is one of the
fundamental issues in optoelectronics for ultrafast optical switching devices. We
have proposed an effective scenario for design of the generation of coherent ring
currents in naphthalene (D2h), which is the smallest unit of planar PAHs. It has
been demonstrated by using quantum chemical calculations and quantum optimal
control (QOC) simulations that two types of ring currents, parallel and
antiparallel, can be generated by resonance excitations by two linearly polarized
lasers. A parallel (antiparallel) ring current means that the currents of two
benzene rings run in the same (opposite) directions. The two types of ring
currents may be experimentally identified by magnetic force microscopy. The QOC
simulations indicate that a parallel ring current can be generated by using
continuous wave and Gaussian pulse lasers with their time delay without relying
on a sophisticated experimental apparatus. The present results provide a guiding
principle of coherent pi-electronics in PAHs for next-generation organic optical
switching devices.
PMID- 28426224
TI - Quantitative Analysis of Polymer Brush Formation Kinetics Using Quartz Crystal
Microbalance: Viscoelasticity of Polymer Brush.
AB - Polymer brush formation kinetics was measured by quartz crystal microbalance
(QCM). In the QCM measurement anomalous complex frequency shift as a function of
graft density was observed: dissipation rate shift DeltaGamma first increased,
showed a peak, and then decreased despite the graft density of the polymer brush
was increasing monotonically. We calculated the shear modulus of the brush layer
from the measured complex frequency shift and revealed that the peak of
DeltaGamma described the crossover from a viscous brush layer to elastic brush
layer. The crossover for the poly(ethylene glycol) with a molecular weight of
2000 occurs at around the characteristic graft density of 0.17 chains/nm2 which
was revealed from the structure analysis by surface plasmon resonance (SPR) and
neutron reflectivity (NR).
PMID- 28426226
TI - Brain Uptake of Bioactive Flavones in Scutellariae Radix and Its Relationship to
Anxiolytic Effect in Mice.
AB - Scutellariae Radix (SR) and its bioactive flavones elicit a variety of effects in
the brain. However, the brain uptake of individual SR flavones and its
relationship to the elicited effects after SR administration remain unknown.
Moreover, previous studies seldom measured pharmacokinetic and pharmacodynamic
outcomes simultaneously. In the current study, the brain uptake of six major SR
flavones and the anxiolytic behavior following oral administration of a SR
extract at two clinically relevant doses (600 and 1200 mg/kg twice daily) were
simultaneously investigated in mice (n = 18 per group). Brain and plasma
concentrations of the flavones were measured by LC-MS/MS, while the anxiolytic
effect was evaluated using the elevated plus maze. To further investigate the
mechanism behind the differential brain uptake of the six SR flavones, these
flavones were separately administered to mice at an equivalent molar oral dose (n
= 6). The brain tissue bindings of the SR flavones were also measured with the in
vitro brain slice method. Our results indicated that all six SR flavones
including three aglycons (baicalein, wogonin, and oroxylin A) and three
glucuronides (baicalin, wogonoside, and oroxyloside) could pass through the blood
brain barrier, with brain concentrations ranging from 7.9 to 224.0 pmol/g. It
provided novel evidence that oroxylin A had the highest brain uptake among the
six SR flavones regardless of its limited content in SR extract, in which 3.6
3.9% of the administered oroxylin A dose was present in the brain 6 h postdosing
and with a brain-to-plasma ratio of 0.42-0.46. Although SR extract contains
flavones that are positive modulators of the benzodiazepine binding site of GABAA
receptors (baicalein, wogonin, and baicalin), our behavioral study for the first
time indicated that SR extract (a mixture of six flavones) did not elicit
significant anxiolytic effect at the studied doses. Oroxylin A also demonstrated
the highest brain uptake when the six flavones were separately administered to
mice, and the highest affinity to brain tissues in the in vitro tissue binding
assay. The high brain uptake of oroxylin A, a GABAA antagonist which had been
reported to antagonize diazepam-induced anxiolytic effect, might have suppressed
the anxiolytic effects of the other flavones and account for the lack of overall
anxiolytic effect of SR extract. The current study illustrates the importance of
monitoring pharmacokinetics in a behavioral study, particularly for herbal
medicines which consist of multiple components that might have different or even
opposite pharmacological effects on the same target.
PMID- 28426227
TI - Monovalent versus Divalent Cation Diffusion in Thiospinel Ti2S4.
AB - Diffusion coefficients (D) for both Li+ and Mg2+ in Ti2S4 were measured using the
galvanic intermittent titration technique (GITT) as a function of both ion
concentration (x) and temperature. During discharge at 60 degrees C, DLi
descends gradually from 2 * 10-8 cm2/s at xLi ~ 0 to 2 * 10-9 cm2/s at xLi ~ 1.9.
In contrast, DMg decreases sharply from 2 * 10-8 to 1 * 10-12 cm2/s by xMg ~ 0.8.
This kinetic factor limits the maximum practical discharge capacity of MgxTi2S4.
The difference in behavior vis a vis Li+ implies that either increasing Mg2+
occupation of the tetrahedral site at xMg > 0.6 and/or interactions between
diffusing cations play a larger role in mediating the diffusion of divalent
compared to monovalent cations. Diffusion activation energies (Ea) extracted from
the temperature-dependent data revealed that Ea,Mg (540 +/- 80 meV) is about
twice that of Ea,Li (260 +/- 50 meV), explaining the poorer electrochemical
performance of MgxTi2S4 at room temperature.
PMID- 28426228
TI - Ultrafast Dynamics of a Triazene: Excited-State Pathways and the Impact of
Binding to the Minor Groove of DNA and Further Biomolecular Systems.
AB - Many synthetic DNA minor groove binders exhibit a strong increase in fluorescence
when bound to DNA. The pharmaceutical-relevant berenil (diminazene aceturate) is
an exception with an extremely low fluorescence quantum yield (on the order of 10
4). We investigate the ultrafast excited-state dynamics of this triazene by
femtosecond time-resolved fluorescence experiments in water, ethylene glycol, and
buffer and bound to the enzyme beta-trypsin, the minor groove of AT-rich DNA, and
G-quadruplex DNA. Ab initio calculations provide additional mechanistic insight.
The complementing studies unveil that the excited-state motion initiated by pipi*
excitation occurs in two phases: a subpicosecond phase associated with the
lengthening of the central N?N double bond, followed by a bicycle-pedal-type
motion of the triazene bridge, which is almost volume-conserving and can proceed
efficiently within only a few picoseconds even under spatially confined
conditions. Our results elucidate the excited-state relaxation mechanism of
aromatic triazenes and explain the modest sensitivity of the fluorescence quantum
yield of berenil even when it is bound to various biomolecules.
PMID- 28426229
TI - Nanofabricated Catalyst Particles for the Investigation of Catalytic Carbon
Oxidation by Oxygen Spillover.
AB - The catalytic oxidation of carbon by molecular oxygen was studied using C/Pt,
Pt/C, Pt/Al2O3/C, Pt/CeO2/C, Al2O3/C, and CeO2/C model samples prepared by hole
mask colloidal lithography. By this technique, the degree of contact between
platinum and carbon was controlled with high precision. The oxidation of carbon
was monitored using atomic force microscopy and scanning electron microscopy. The
results show that Pt in direct contact with carbon catalyzes the oxidation of
carbon by spillover of dissociated oxygen from Pt to carbon. By physically
separating Pt and carbon with a 10 nm thin spacer layer of Al2O3, the oxygen
spillover was entirely blocked. However, through a corresponding spacer layer of
CeO2, carbon oxidation was still observed, either by oxygen spillover from Pt to
carbon or directly dissociated on the ceria, although at a slower rate compared
to the case with no spacer layer between Pt and carbon.
PMID- 28426230
TI - Photophysics and Excited-State Properties of Cyclometalated Iridium(III)
Platinum(II) and Iridium(III)-Iridium(III) Bimetallic Complexes Bridged by
Dipyridylpyrazine.
AB - We investigated the electrochemical and excited-state properties of 2,3-bis(2
pyridyl)pyrazine (dpp)-bridged bimetallic complexes, (L)2Ir-dpp-PtCl [1, L = 2
(4',6'-difluorophenyl)pyridinato-N,C2 (dfppy); 2, L = 2-phenylpyridinato-N,C2
(ppy)] and [(L)2Ir]2(dpp) [3, L = dfppy; 4, L = ppy] compared to monometallic
complexes, (L)2Ir-dpp (5, L = dfppy; 6, L = ppy) and dpp-PtCl (dpp-PtIICl2; 7).
The single-crystal X-ray crystallographic structures of 1, 3, 5, and 6 showed
that 1 and 3 have approximately coplanar structures of the dpp unit, while the
noncoordinated pyridine ring of dpp in 5 and 6 is largely twisted with respect to
the pyrazine ring. We found that the properties of the bimetallic complex
significantly depended on the electronic and geometrical modulations of each
fragment: (1) electronic structure of the main L (C^N) ligand in an iridium
chromophore (L = dfppy or ppy) and (2) planarity of the bridging ligand (dpp).
Their electrochemical and photophysical properties revealed that efficient
electron-transfer processes predominated in the bimetallic systems regardless of
the second metal participation. The low efficiencies of photoluminescence of dpp
bridged Ir-Pt and Ir-Ir bimetallic complexes (1-4) could be explained by assuming
the involvement of crossing to platinum- and iridium-based d-d states from the
emissive state. Such stereochemical and electronic situations around dpp allowed
thermally activated crossing to platinum- and iridium-based d-d states from the
emissive triplet metal-to-ligand charge-transfer (3MLCT) state, followed by
cleavage of the dpp-Pt and (L)2Ir-dpp bonds. The transient absorption study
further confirmed that the planarity of the dpp bridging ligand, which was
defined as the magnitude of tilt between the pyridine ring and pyrazine, had a
direct correlation with the degree of nonradiative decay from the emissive
iridium-based 3MLCT to the Ir d-d or Pt d-d state, leading to photoinduced
dissociation of bimetallic complexes. From the dissociation pattern of metal
complexes analyzed after photoirradiation, we found that their dissociation
pathways were directly related to the quenching direction (either Ir d-d or Pt d
d) with a significant dependency on the relative 3MLCT levels of the (L)2Ir-dpp
component.
PMID- 28426231
TI - The Prevalence of Integrons as the Carrier of Antibiotic Resistance Genes in
Natural and Man-Made Environments.
AB - Class 1 integrase intI1 has been considered as a good proxy for anthropogenic
pollution because of being linked to genes conferring resistance to antibiotics.
The gene cassettes of class 1 integrons could carry diverse antibiotic resistance
genes (ARGs) and conduct horizontal gene transfer among microorganisms. The
present study applied high-throughput sequencing technique combined with an intI1
database and genome assembly to quantify the abundance of intI1 in 64
environmental samples from 8 ecosystems, and to investigate the diverse
arrangements of ARG-carrying gene cassettes (ACGCs) carried by class 1 integrons.
The abundance of detected intI1 ranged from 3.83 * 10-4 to 4.26 * 10 degrees
intI1/cell. High correlation (Pearson's r = 0.852) between intI1 and ARG
abundance indicated that intI1 could be considered as an important indicator of
ARGs in environments. Aminoglycoside resistance genes were most frequently
observed on gene cassettes, carried by 57% assembled ACGCs, followed by
trimethoprim and beta-lactam resistance genes. This study established the
pipeline for broad monitoring of intI1 in various environmental samples and
scanning the ARGs carried by integrons. These findings supplemented our knowledge
on the distribution of class 1 integrons and ARGs carried on mobile genetic
elements, benefiting future studies on horizontal gene transfer of ARGs.
PMID- 28426232
TI - Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa
H in Lipid Micelles.
AB - With the rise in antibiotic resistance, antimicrobial peptides (AMPs) show
promise for therapeutic development, but higher specificity is required. PGLa-H
is a naturally occurring decapeptide, reported to have moderate antibacterial
activity and low hemolytic activity, with its sequence being identical to that of
the C-terminal fragment of highly selective AMP, PGLa. DiPGLa-H, a sequential
tandem repeat of PGLa-H, and Kiadin, an analogue with a Val to Gly substitution
at position 15, display improved in vitro bactericidal activity against both Gram
negative and Gram-positive pathogens, with generally low toxicity for human
cells. Despite Gly being a more flexible residue, NMR structural studies showed
little difference in structure and dynamics between the two peptides for the
first 14 residues, with somewhat greater flexibility in the C-terminus of Kiadin
resulting in a tighter structure of the peptide in the presence of sodium dodecyl
sulfate micelles. AMPs found in organisms often exhibit minimal amino acid
mutations, and such small differences in peptide conformation may be utilized to
design more selective AMPs.
PMID- 28426233
TI - Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage
Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human
Dihydrofolate Reductases.
AB - Drug design by methods such as fragment screening requires effective
solubilization of millimolar concentrations of small organic compounds while
maintaining the properties of the biological target. We investigate four organic
solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs)
as cosolvents to establish conditions for screening two structurally unrelated
dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate
concentrations (10%-15%) of cosolvents had little effect on inhibition of the
microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations
of organic cosolvents generally decreased activity of both DHFRs. In contrast, a
specific IL conserved the activity of one DHFR, while severely reducing the
activity of the other, and vice versa, illustrating the differing effect of ILs
on distinct protein folds. Most of the cosolvents investigated preserved the fold
of R67 DHFR and had little effect on binding of the cofactor NADPH, but reduced
the productive affinity for its substrate. In contrast, cosolvents resulted in
modest structural destabilization of hDHFR with little effect on productive
affinity. We conclude that the organic cosolvents, methanol, dimethylformamide,
and dimethylsulfoxide, offer the most balanced conditions for early-stage
compound screening as they maintain sufficient biological activity of both DHFRs
while allowing for compound dissolution in the millimolar range. However, IL
cosolvents showed poor capacity to solubilize organic compounds at millimolar
concentrations, mitigating their utility in early-stage screening. Nonetheless,
ILs could provide an alternative to classical organic cosolvents when low
concentrations of inhibitors are used, as when characterizing higher affinity
inhibitors.
PMID- 28426234
TI - The OTOGL p.Arg925* Variant is Associated with Moderate Hearing Loss in a Syrian
Nonconsanguineous Family.
AB - AIM: To screen for the genetic basis of congenital hearing loss in a Syrian
family. METHODS: A Syrian patient living in Lebanon presented with moderate
congenital hearing loss. The patient's large nonconsanguineous family was
recruited. DNA was extracted from blood samples and sent for whole-exome
sequencing. A detailed clinical examination along with audiograms was obtained
for all subjects. RESULTS: Hearing loss was noted to be mild to moderate in the
low and mid frequencies, sloping to moderate to severe in the high frequencies
for all affected members. Results of DNA analysis showed the presence of a
previously described p.Arg925* mutation in the OTOGL gene on both alleles in
affected family members, whereas nonaffected members either had the wild type or
one copy of the mutated allele. DISCUSSION: Mutations affecting the OTOGL gene
have been recently connected with nonsyndromic sensorineural hearing loss. Seven
such mutations have already been described. The p.Arg925* reported in this study
has been found once in a French family. The current report is the first to
describe this mutation in a Middle Eastern family.
PMID- 28426235
TI - Expressive social support buffers the impact of care-related work interruptions
on caregivers' depressive symptoms.
AB - OBJECTIVE: To assess if expressive and instrumental social support from family
and friends moderate the association of care-related work interruptions (e.g.
leaving work for the older adult's doctor appointment) with depressive symptoms
among working family caregivers of older adults. METHODS: Data were from the
Singapore Survey on Informal Caregiving (SSIC). A subsample of 662 dyads, each
comprising an older care-recipient [home-dwelling Singaporean aged 75 and older
receiving human assistance for at least one activity of daily living (ADL)] and
his/her working family caregiver, was analysed. Caregiver depressive symptoms
were assessed using the Center for Epidemiologic Studies Depression scale. Care
related work interruptions were scaled through the Mokken scaling procedure.
Expressive social support was assessed using a scale by Pearlin and co-workers.
Instrumental social support was based on the hours of ADL help provided to the
care-recipient by any family member or friend, on behalf of the primary
caregiver. A linear regression model, with interaction terms, assessed expressive
and instrumental social support as moderators of the association of care-related
work interruptions with caregiver depressive symptoms. RESULTS: More care-related
work interruptions were associated with more caregiver depressive symptoms. And,
this association was moderated by expressive, but not instrumental, social
support. CONCLUSION: Our findings conform to previous qualitative work suggesting
that caregivers' mental health may not benefit from instrumental support, but
from receiving expressive support instead. Initiatives for improving the care
experience of working caregivers of older adults should focus on promoting
expressive support from their friends and family.
PMID- 28426236
TI - RNA Extracted from Formalin-Fixed, Paraffin-Embedded Renal Biopsy Biospecimens:
An Evaluation of Alternative Extraction Kits and the Effects of Storage Time.
PMID- 28426237
TI - On the Complexity of Item Response Theory Models.
AB - Complexity in item response theory (IRT) has traditionally been quantified by
simply counting the number of freely estimated parameters in the model. However,
complexity is also contingent upon the functional form of the model. We examined
four popular IRT models-exploratory factor analytic, bifactor, DINA, and DINO
with different functional forms but the same number of free parameters. In
comparison, a simpler (unidimensional 3PL) model was specified such that it had 1
more parameter than the previous models. All models were then evaluated according
to the minimum description length principle. Specifically, each model was fit to
1,000 data sets that were randomly and uniformly sampled from the complete data
space and then assessed using global and item-level fit and diagnostic measures.
The findings revealed that the factor analytic and bifactor models possess a
strong tendency to fit any possible data. The unidimensional 3PL model displayed
minimal fitting propensity, despite the fact that it included an additional free
parameter. The DINA and DINO models did not demonstrate a proclivity to fit any
possible data, but they did fit well to distinct data patterns. Applied
researchers and psychometricians should therefore consider functional form-and
not goodness-of-fit alone-when selecting an IRT model.
PMID- 28426238
TI - Predictive Low-Glucose Suspend to Prevent Hypoglycemia.
PMID- 28426239
TI - Performance of an Artificial Pancreas System for Young Children with Type 1
Diabetes.
AB - BACKGROUND: Young children 5-8 years old with type 1 diabetes (T1D) exhibit clear
needs for improved glycemic control but may be limited in their ability to safely
interact with an artificial pancreas system. Our goal was to evaluate the safety
and performance of an artificial pancreas (AP) system among young children with
T1D. RESEARCH DESIGN AND METHODS: In a randomized, crossover trial, children with
T1D age 5-8 years were enrolled to receive on separate study periods (in random
order) either the UVa AP using the DiAs Control Platform software with child
resistant lock-out screens (followed as an out-patient admission) or their usual
insulin pump+continuous glucose monitor (CGM) care at home. Hypoglycemic events
and CGM tracings were compared between the two 68-h study periods. All analyses
were adjusted for level of physical activity as tracked using Fitbit devices.
RESULTS: Twelve participants (median age 7 years, n = 6 males) completed the
trial. Compared to home care, the AP admission resulted in increased time with
blood glucose (BG) 70-180 mg/dL (73% vs. 47%) and lower mean BG (152 mg/dL vs.
190 mg/dL), both P < 0.001 after adjustment for activity. Occurrence of
hypoglycemia was similar between sessions without differences in time <70 mg/dL
(AP 1.1% +/- 1.1%; home 1.6% +/- 1.2%). There were no adverse events during the
AP or home study periods. CONCLUSIONS: Use of an AP in young children was safe
and resulted in improved mean BG without increased hypoglycemia. This suggests
that AP use in young children is safe and improves overall diabetes control.
ClinicalTrials.gov registration number: NCT02750267.
PMID- 28426240
TI - Influence of Glenoid Defect Size and Bone Fragment Size on the Clinical Outcome
After Arthroscopic Bankart Repair in Male Collision/Contact Athletes.
AB - BACKGROUND: The usefulness of arthroscopic Bankart repair for collision/contact
athletes has varied in previous reports. PURPOSE: To investigate the influence of
glenoid rim morphologic characteristics on the clinical outcome after
arthroscopic Bankart repair without additional reinforcement procedures in male
collision/contact athletes, including athletes with a large glenoid defect. STUDY
DESIGN: Case-control study; Level of evidence, 3. METHODS: Eighty-six athletes
(93 shoulders) followed for a minimum of 2 years were retrospectively
investigated. The sports were rugby (36 shoulders), American football (29
shoulders), and other collision/contact sports (28 shoulders). Preoperative
glenoid defect size, bone fragment size, and bone union after bony Bankart repair
were investigated regarding factors influencing postoperative recurrence.
Postoperative changes in glenoid defect size and bone fragment size were
investigated as well as their influence on the clinical outcome. RESULTS:
Postoperative recurrence of instability was noted in 22 shoulders (23.7%). The
recurrence rate was 33.3% in rugby, 17.2% in American football, and 17.9% in
other collision/contact sports. The recurrence rate was only 7.1% in 28 shoulders
without a preoperative glenoid defect, but it increased to 43.8% in 16 shoulders
that did not have a bone fragment even though there was a preoperative glenoid
defect. Additionally, the recurrence rate was 7.7% in 26 shoulders with bone
union after arthroscopic bony Bankart repair but rose to 45% in 20 shoulders
without bone union. In the shoulders with bone union, the mean bone fragment size
increased from 8.2% preoperatively to 15.2% postoperatively, while the mean
glenoid defect size decreased from 18.0% to 2.8%, respectively. The recurrence
rate was 8.3% in shoulders with a final glenoid defect 5% or less versus 38.1% in
shoulders with a defect greater than 5%. While the recurrence rate was low among
athletes other than rugby players with a final defect of 10% or less, it was low
in only the rugby players with a defect of 0%. CONCLUSION: In male
collision/contact athletes, while the overall clinical outcome was
unsatisfactory, a favorable outcome was achieved in athletes without a
preoperative glenoid defect and athletes with bone union. The glenoid defect
decreased in size postoperatively due to remodeling of the united bone fragment,
and the recurrence rate was low when the final glenoid defect size was 5% or
less.
PMID- 28426241
TI - Extracellular Heme Uptake and the Challenge of Bacterial Cell Membranes.
AB - Iron is essential for the survival of most bacteria but presents a significant
challenge given its limited bioavailability. Furthermore, the toxicity of iron
combined with the need to maintain physiological iron levels within a narrow
concentration range requires sophisticated systems to sense, regulate, and
transport iron. Most bacteria have evolved mechanisms to chelate and transport
ferric iron (Fe3+) via siderophore receptor systems, and pathogenic bacteria have
further lowered this barrier by employing mechanisms to utilize the host's
hemoproteins. Once internalized, heme is cleaved by both oxidative and
nonoxidative mechanisms to release iron. Heme, itself a lipophilic and toxic
molecule, presents a significant challenge for transport into the cell. As such,
pathogenic bacteria have evolved sophisticated cell surface signaling and
transport systems to obtain heme from the host. In this review, we summarize the
structure and function of the heme-sensing and transport systems of pathogenic
bacteria and the potential of these systems as antimicrobial targets.
PMID- 28426242
TI - Cellular Electron Cryotomography: Toward Structural Biology In Situ.
AB - Electron cryotomography (ECT) provides three-dimensional views of macromolecular
complexes inside cells in a native frozen-hydrated state. Over the last two
decades, ECT has revealed the ultrastructure of cells in unprecedented detail. It
has also allowed us to visualize the structures of macromolecular machines in
their native context inside intact cells. In many cases, such machines cannot be
purified intact for in vitro study. In other cases, the function of a structure
is lost outside the cell, so that the mechanism can be understood only by
observation in situ. In this review, we describe the technique and its history
and provide examples of its power when applied to cell biology. We also discuss
the integration of ECT with other techniques, including lower-resolution
fluorescence imaging and higher-resolution atomic structure determination, to
cover the full scale of cellular processes.
PMID- 28426243
TI - Analysis of 2019 Patients Undergoing Revision Anterior Cruciate Ligament
Reconstruction From a Community-Based Registry.
AB - BACKGROUND: Knowledge of patient characteristics, surgical fixation, graft
choice, outcomes, and concurrent injuries of revision anterior cruciate ligament
reconstruction (ACLR) is limited. PURPOSE: To describe the current cohort of
revision ACLR captured by a community registry and the outcomes observed in the
registered patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
Patients who underwent revision ACLR registered between February 2005 and June
2014, by 200 surgeons in 46 hospitals, were evaluated. The Kaiser Permanente ACLR
Registry (KPACLRR) collected data intraoperatively and postoperatively using
paper forms, electronic medical records, administrative claims data, and patient
reported outcomes. The KPACLRR cohort was longitudinally followed, and outcomes
were prospectively ascertained. Outcomes (ie, revisions, subsequent operative
procedures, deep surgical site infections, and deep venous thrombosis) were
adjudicated via a chart review. Descriptive statistics were employed. RESULTS: Of
2019 patients who underwent revision ACLR, at a median follow-up of 2.2 years
(interquartile range, 1.0-3.8 years), 212 (10.5%) required subsequent operative
procedures, and 86 (4.3%) were revised a second time. At the time of revision,
55.1% of the patients had at least 1 concurrent meniscal injury, and 26% of those
were repairable. Cartilage injuries were present in 42.0% of patients. Deep
surgical site infections occurred in 12 patients (0.6%), deep venous thrombosis
occurred in 5 patients (0.3%), and 1 patient (0.1%) had a pulmonary embolism.
CONCLUSION: Revision ACLR can be performed with a low short-term revision rate
and relatively few complications. At the time of revision, nearly half of these
patients had an irreparable meniscal injury, and slightly less than half had a
cartilage injury. A large community-based ACLR registry is useful in informing
surgeons of current treatment practices, prevalence of concurrent injuries, and
outcomes associated with the procedures, especially infrequent procedures such as
revision ACLR.
PMID- 28426244
TI - Piperine Triggers Apoptosis of Human Oral Squamous Carcinoma Through Cell Cycle
Arrest and Mitochondrial Oxidative Stress.
AB - Piperine is a nitrogenous pungent substance exhibiting multifunctional
pharmacological properties. However, the mechanism underlying its anticancer
potential is not well elucidated in human oral squamous carcinoma (KB) cell line.
The anticancer potential of piperine was evaluated through potent biomarkers viz.
reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial
membrane potential (MMP). In addition, cell cycle kinetics and caspases-3
activity were also carried out to confirm anticancer activity of piperine.
Results showed that various concentrations (25-300 MUM) of piperine exposure
reduced the cell viability of KB cells significantly (P < 0.01). Piperine induced
significant (P < 0.01) dose-related increment in ROS production and nuclear
condensation. Moreover, piperine stimulated cell death by inducing loss of MMP,
and caspase-3 activation. Cell cycle study revealed that piperine arrested the
cells in G2/M phase and decreased the DNA content. Findings of this study suggest
the efficacy of piperine in inducing cell death via the decrease in MMP and ROS
liberation followed by caspase-3 activation and cell cycle arrest. Further
assessment of the anticancer potency of piperine is needed for anticancer drug
development.
PMID- 28426245
TI - Visualizing Tensions in an Ethnographic Moment: Images and Intersubjectivity.
AB - Images function as sources of data and influence our thinking about fieldwork,
representation, and intersubjectivity. In this article, I show how both the
ethnographic relationships and the working method of photography lead to a more
nuanced understanding of a healing event. I systematically analyze 33 photographs
made over a 15-minute period during the preparation and application of a poultice
(topical cure) in a rural Andean home. The images chronicle the event, revealing
my initial reaction and the decisions I made when tripping the shutter. By
unpacking the relationship between ethnographer and subject, I reveal the
constant negotiation of positions, assumptions, and expectations that make up
intersubjectivity. For transparency, I provide thumbnails of all images,
including metadata, so that readers may consider alternative interpretations of
the images and event.
PMID- 28426246
TI - Biofilm characteristics and evaluation of the sanitation procedures of
thermophilic Aeribacillus pallidus E334 biofilms.
AB - The ability of Aeribacillus pallidus E334 to produce pellicle and form a biofilm
was studied. Optimal biofilm formation occurred at 60 degrees C, pH 7.5 and 1.5%
NaCl. Extra polymeric substances (EPS) were composed of proteins and eDNA (21.4
kb). E334 formed biofilm on many surfaces, but mostly preferred polypropylene and
glass. Using CLSM analysis, the network-like structure of the EPS was observed.
The A. pallidus biofilm had a novel eDNA content. DNaseI susceptibility (86.8%
removal) of eDNA revealed its importance in mature biofilms, but the purified
eDNA was resistant to DNaseI, probably due to its extended folding outside the
matrix. Among 15 cleaning agents, biofilms could be removed with alkaline
protease and sodium dodecyl sulphate (SDS). The removal of cells from
polypropylene and biomass on glass was achieved with combined SDS/alkaline
protease treatment. Strong A. pallidus biofilms could cause risks for industrial
processes and abiotic surfaces must be taken into consideration in terms of
sanitation procedures.
PMID- 28426247
TI - Response to Letter on Immunoassays for Field Screening of Bacillus anthracis and
Ricin.
PMID- 28426248
TI - Variability in neurocognitive performance: Age, gender, and school-related
differences in children and from ages 6 to 12.
AB - Cognitive development in children presents peculiarities according to groups of
age, gender, and type of school. Few studies have been investigating the effects
of all these factors. The aim of this study was to investigate the main effects
and the interactions of age, gender, and type of school in 419 children from ages
6 to 12 years old evaluated by the Child Brief Neuropsychological Assessment
Battery (NEUPSILIN-Inf). Older children, children in private schools and girls
presented better results. Interactions between all three independent variables
were observed in different cognitive domains. The results highlight both the
heterogeneity and the influence of multiple factors in children's
neuropsychological development.
PMID- 28426249
TI - Non-Enzymatic Electrochemistry in Characterization and Analysis of Steroid
Compounds.
AB - This review summarizes achievements in electrochemistry-related research of
steroid-based compounds in clinical, pharmaceutical, and environmental analysis.
Special attention is paid to compounds possessing none or only isolated double
bonds at the steroid core. Their direct redox activity is limited to far
positive/negative potentials under variety of conditions and electrode materials
and relies on the functional groups attached to the steroid skeleton, or as the
case may be its double bond or moieties present at the side chain. The
possibilities of electroanalytical methods in sterol characterization and
analysis are demonstrated in a table with 31 references devoted to direct
voltammetric and amperometric methods of oxidation of cholesterol, phytosterols,
oxysterols, and related compounds at carbon-based and metal-based nanoparticles
modified electrodes, and the reduction of bile acids and their conjugates at
mercury-based electrodes, and modified glassy carbon electrodes. Furthermore,
methods based on the indirect oxidation of cholesterol using bromine species as a
mediator at platinum electrode and non-enzymatic cholesterol biosensors are
reviewed. Their drawbacks and benefits are discussed with respect to the
challenging task of identification and quantitation of these compounds in
biological matrices, otherwise mostly performed using expensive mass
spectrometric techniques preceded by a chromatographic separation step.
PMID- 28426250
TI - Processed Meat and Colorectal Cancer Risk: A Pooled Analysis of Three Italian
Case-Control Studies.
AB - To add evidence to the limited data available from southern Europe, we assessed
the association between processed meat consumption and colorectal cancer risk. We
analyzed data from three case-control studies conducted between 1985 and 2010 in
various Italian areas, including a total of 3745 incident cases and 6804 hospital
based controls. We calculated odds ratios (ORs) and 95% confidence intervals
(CIs) by unconditional multiple logistic regression models. The median
consumption of processed meat was around 20 g/day both in cases and controls. The
OR of colorectal cancer was 1.02 (95% CI 0.99-1.04) for an increase of 10 g/day
of processed meat. The association was statistically significant for colon cancer
(OR 1.03, 95% CI 1.00-1.06), particularly for proximal colon cancer (OR 1.09, 95%
CI 1.04-1.14), while there was no relation with rectal cancer (OR 0.99, 95% CI
0.95-1.03). The OR of proximal colon cancer was 1.38 (95% CI 1.08-1.75) for the
highest sex-specific tertile of consumption (>25 g/day for men, >21.5 for women)
compared with the lowest (<15 g/day), whereas no significant ORs were found for
other anatomical subsites. Our findings indicate that there is no association
with colorectal cancer overall, in the presence, however, of a positive
association with proximal colon cancer.
PMID- 28426251
TI - Current Concepts of the Anterolateral Ligament of the Knee: Anatomy,
Biomechanics, and Reconstruction.
AB - In 1879, Paul Segond described an avulsion fracture (now known as a Segond
fracture) at the anterolateral proximal tibia with the presence of a fibrous band
at the location of this fracture. Although references to this ligament were
occasionally made in the anatomy literature after Segond's discovery, it was not
until 2012 that Vincent et al named this ligament what we know it as today, the
anterolateral ligament (ALL) of the knee. The ALL originates near the lateral
epicondyle of the distal femur and inserts on the proximal tibia near Gerdy's
tubercle. The ALL exists as a ligamentous structure that comes under tension
during internal rotation at 30 degrees . In the majority of specimens, the ALL
can be visualized as a ligamentous structure, whereas in some cases it may only
be palpated as bundles of more tense capsular tissue when internal rotation is
applied. Biomechanical studies have shown that the ALL functions as a secondary
stabilizer to the anterior cruciate ligament (ACL) in resisting anterior tibial
translation and internal tibial rotation. These biomechanical studies indicate
that concurrent reconstruction of the ACL and ALL results in significantly
reduced internal rotation and axial plane tibial translation compared with
isolated ACL reconstruction (ACLR) in the presence of ALL deficiency. Clinically,
a variety of techniques are available for ALL reconstruction (ALLR). Current
graft options include the iliotibial (IT) band, gracilis tendon autograft or
allograft, and semitendinosus tendon autograft or allograft. Fixation angle also
varies between studies from full knee extension to 60 degrees to 90 degrees of
flexion. To date, only 1 modern study has described the clinical outcomes of
concomitant ALLR and ACLR: a case series of 92 patients with a minimum 2-year
follow-up. Further studies are necessary to define the ideal graft type, location
of fixation, and fixation angle for ALLR. Future studies also must be designed in
a prospective comparative manner to compare the clinical outcomes of patients
undergoing ACLR with ALL reconstruction versus without ALL reconstruction. By
discovering the true effect of the ALL, investigators can elucidate the
importance of ALLR in the setting of an ACL tear.
PMID- 28426252
TI - Intervention Effects on Stage of Change Membership and Transitions among
Adolescent Energy Balance Behaviors.
AB - The transition from childhood to adolescence is a crucial period for the
development of healthy behaviors to be sustained later in life. With obesity a
leading public health problem, the promotion of healthy behaviors has the
potential to make a huge impact. The current study evaluated Stage of Change
progression in a large (N = 4158) computer-delivered, Transtheoretical Model
tailored intervention focusing on physical activity and fruit and vegetable
consumption (FV). Markov models were used to explore stage transitions and
patterns of discrete change from sixth to ninth grade. Nested model comparisons
examined the consistency of these patterns across time and intervention
condition. Major findings supported models in which participants were free to
transition forward and backward to any of the stages, but higher probabilities
were observed for remaining in the same stage or for transitioning one or two
stages forward. Participants in the intervention group had higher probabilities
of transitioning toward Maintenance, with more change occurring relative to the
comparison group during transitions from grades six to eight but not for grades
eight to nine.
PMID- 28426253
TI - Using Computerized Mental Health Programs in Alternative Education: Understanding
the Requirements of Students and Staff.
AB - : Computerized cognitive behavioral therapy (cCBT) programs have been shown to be
both acceptable and effective with youth. However, their use with more vulnerable
youth, such as early school leavers, remains relatively unstudied. This study
explored student and staff attitudes toward the use of cCBT in an alternative
education setting. METHODS: Student and staff needs were assessed using the
Requirements development approach (Van Velsen, Wentzel, & Van Gemert-Pijnen,
2013). An online staff survey (n = 16) was conducted to provide information on
the context of delivery, and stakeholder requirements were further explored in
four student workshops (n = 32) and staff group discussions (n = 12). RESULTS:
Students' requirements in relation to program look and feel were reflective of
issues with literacy and concentration. Activity- rather than text-based programs
were considered easier to learn from, whereas attractive design with features
such as connecting with others were thought necessary to keep young people
engaged. Students wanted to learn practical skills on improving their mental
health and well-being, using content that is positive, encouraging, and credible
and that can be tailored to individual needs. Anonymity and voluntary
participation were considered essential when delivering cCBT in the context of
alternative education, as well as additional access from home to ensure
timeliness of support. Staff required both flexibility and careful planning and
timetabling in order to deliver cCBT in the alternative education setting and to
support student engagement. CONCLUSION: The findings provide novel insight into
the needs and preferences of vulnerable youth, with important implications for
the implementation of computerized mental health programs in alternative
education settings. A better understanding of user needs and preferences is
critical for improving the uptake and impact of e-mental health resources.
PMID- 28426254
TI - Naringin protects viscera from ischemia/reperfusion injury by regulating the
nitric oxide level in a rat model.
AB - We investigated the effects of naringin on small intestine, liver, kidney and
lung recovery after ischemia/reperfusion (I/R) injury of the gut. Rats were
divided randomly into four groups of eight. Group A was the sham control; group B
was ischemic for 2 h; group C was ischemic for 2 h and re-perfused for 2 h (I/R);
group D was treated with 50 mg/kg naringin after ischemia, then re-perfused for 2
h. Endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase
(iNOS) expressions were detected by immunolabeling. We also measured arginase
activity, amounts of nitric oxide (NO) and total protein. iNOS was increased
significantly in the small intestine, liver and kidney in group C. iNOS was
decreased significantly only in small intestine and lung in group D. eNOS was
increased significantly in the small intestine, liver and lung in group C. eNOS
was decreased in small intestine, liver and lung in group D; however, eNOS was
decreased in the kidney in group C and increased in the kidney in group D. The
amount of NO was decreased significantly in all tissues in group D, but arginase
activity was decreased in the small intestine and lung, increased in the kidney
and remained unchanged in the liver in group D. The total protein increased in
the small intestine and liver in group D, but decreased significantly in the
kidney and lung in group D. Naringin had significant, salutary effects on the
biochemical parameters of I/R by decreasing the NO level, equilibrating iNOS and
eNOS expressions, and decreasing arginase activity.
PMID- 28426255
TI - Pregabalin for the treatment of neuropathic pain: a narrative review for primary
care providers.
AB - BACKGROUND: Neuropathic pain (NeP) is a distinct type of pain caused by damage to
the nervous system itself. This often severe and chronic type of pain requires
specific treatments that target the underlying pain pathophysiology. AIM: The
purpose of the current narrative review is to provide an overview of pregabalin
(Lyrica 1 ) for the treatment of NeP including its effects on pain, pain-related
sleep interference, and other health-related outcomes, timing of therapeutic
effect, safety and tolerability, and dosing. The information provided here will
help primary care providers develop more effective NeP treatment strategies.
PMID- 28426256
TI - Effects of Foeniculum vulgare essential oil compounds, fenchone and limonene, on
experimental wound healing.
AB - We investigated the wound healing efficacy of the Foeniculum vulgare compounds,
fenchone and limonene, using an excisional cutaneous wound model in rats. An
excision wound was made on the back of the rat and fenchone and limonene were
applied topically to the wounds once daily, separately or together, for 10 days.
Tissue sections from the wounds were evaluated for histopathology. The healing
potential was assessed by comparison to an untreated control group and an olive
oil treated sham group. We scored wound healing based on epidermal regeneration,
granulation tissue thickness and angiogenesis. After day 6, wound contraction
with limonene was significantly better than for the control group. Ten days after
treatment, a significant increase was observed in wound contraction and re
epithelialization in both fenchone and limonene oil treated groups compared to
the sham group. Groups treated with fenchone and with fenchone + limonene scored
significantly higher than the control group, but the difference was not
statistically significant compared to the olive oil treated group. Our findings
support the beneficial effects of fenchone and limonene for augmenting wound
healing. The anti-inflammatory and antimicrobial activities of fenchone and
limonene oil increased collagen synthesis and decreased the number of
inflammatory cells during wound healing and may be useful for treating skin
wounds.
PMID- 28426257
TI - Facial eschar following a single application of black salve.
AB - A previously healthy 86-year-old male was transported by ambulance to the trauma
bay of the emergency department (ED) for profuse bleeding from the left temple.
The ambulance crew raised concern that the volume and force of the bleed may
suggest arterial involvement. The patient reported having applied a natural
topical remedy to a mole two weeks prior at the recommendation of a naturopath.
The patient described progressive blackening and swelling of the area in the days
following the single application of the product. After gaining control of the
bleeding in the ED, the area was found to have a raised, 2 cm eschar.
PMID- 28426258
TI - Improvements in Out-of-Hospital Cardiac Arrest Survival from 1998 to 2013.
AB - OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) remains a major public health
burden. Aggregate OHCA survival to hospital discharge has reportedly remained
unchanged at 7.6% for almost 30 years from 1970 to 2008. We examined the trends
in adult OHCA survival over a 16-year period from 1998 to 2013 within a single
EMS agency. METHODS: Observational cohort study of adult OHCA patients treated by
Tualatin Valley Fire & Rescue (TVF&R) from 1998 to 2013. This is an ALS first
response fire agency that maintains an active Utstein style cardiac arrest
registry and serves a population of approximately 450,000 in 9 incorporated
cities in Oregon. Primary outcomes were survival to hospital discharge in all
patients and in the subgroup with witnessed ventricular fibrillation/pulseless
ventricular tachycardia (VF/VT). The impact of key covariates on survival was
assessed using univariate logistic regression. These included patient factors
(age and sex), event factors (location of arrest, witnessed status, and first
recorded cardiac arrest rhythm), and EMS system factors (response time interval,
bystander CPR, and non-EMS AED shock). We used multivariate logistic regression
to examine the impact of year increment on survival after multiple imputation for
missing data. Sensitivity analysis was performed with complete cases. RESULTS:
During the study period, 2,528 adult OHCA had attempted field resuscitation. The
survival rate for treated cases increased from 6.7% to 18.2%, with witnessed
VF/VT cases increasing from 14.3% to 31.4% from 1998 to 2013. Univariate analysis
showed that younger age, male sex, public location of arrest, bystander or EMS
witnessed event, initial rhythm of pulseless electrical activity (PEA) or VF/VT,
bystander CPR, non-EMS AED shock, and a shorter EMS response time were
independently associated with survival. After adjustment for covariates, the odds
of survival increased by 9% (OR 1.09, 95%CI: 1.05-1.12) per year in all treated
cases, and by 6% (OR 1.06, 95% 1.01-1.10) per year in witnessed VF/VT subgroups.
Findings remained consistent on sensitivity analysis. CONCLUSIONS: Overall
survival from treated OHCA has increased over the last 16 years in this
community. These survival increases demonstrate that OHCA is a treatable
condition that warrants further investigation and investment of resources.
PMID- 28426259
TI - The Sernbo score predicts 1-year mortality after displaced femoral neck fractures
treated with a hip arthroplasty.
AB - Background and purpose - Displaced femoral neck fractures (FNFs) are associated
with high rates of mortality during the first postoperative year. The Sernbo
score (based on age, habitat, mobility, and mental state) can be used to stratify
patients into groups with different 1-year mortality. We assessed this predictive
ability in patients with a displaced FNF treated with a hemiarthroplasty or a
total hip arthroplasty. Patients and methods - 292 patients (median age 83 (65
99) years, 68% female) with a displaced FNF were included in this prospective
cohort study. To predict 1-year mortality, we used a multivariate logistic
regression analysis including comorbidities and perioperative management. A
receiver operating characteristic (ROC) analysis was used to evaluate the
predictive ability of the Sernbo score, which was subsequently divided in a new
manner into a low, intermediate, or high risk of death during the first year.
Results - At 1-year follow-up, the overall mortality rate was 24%, and in
Sernbo's low-, intermediate-, and high-risk groups it was 5%, 22%, and 51%,
respectively. The Sernbo score was the only statistically significant predictor
of 1-year mortality: odds ratio for the intermediate-risk group was 4.2 (95% Cl:
1.5-12) and for the high-risk group it was 15 (95% CI: 5-40). The ROC analysis
showed a fair predictive ability of the Sernbo score, with an area under the
curve (AUC) of 0.79 (95% CI: 0.73-0.83). Using a cutoff of less than 11 points on
the score gave a sensitivity of 61% and a specificity of 83%. Interpretation -
The Sernbo score identifies patients who are at high risk of dying in the first
postoperative year. This scoring system could be used to better tailor
perioperative care and treatment in patients with displaced FNF.
PMID- 28426260
TI - The effects of intermittent use of the SGLT-2 inhibitor, dapagliflozin, in
overweight patients with type 2 diabetes in Japan: a randomized, crossover,
controlled clinical trial.
AB - BACKGROUND: This study examined the effects of short-term administration of the
sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat
area (VFA) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND
METHODS: In this randomized, crossover, controlled clinical trial, overweight
patients with type 2 diabetes were randomized to treatment with 5 mg
dapagliflozin for the first (n = 27) or second 12-week study period (n = 29). The
parameters evaluated at baseline and after 12 and 24 weeks included blood
pressure, hemoglobin A1c (HbA1c), body composition, VFA, and subcutaneous fat
area (SFA). RESULTS: In both groups, dapagliflozin administration improved the
levels of HbA1c, body weight, blood pressure, total fat mass, and VFA. Cessation
of dapagliflozin, however, reversed the improvements in HbA1c, blood pressure,
body weight, and SFA levels, whereas reductions in VFA and total fat mass levels
were somewhat maintained even after 12 weeks without treatment. CONCLUSIONS:
Dapagliflozin led to decreases in VFA and, consequently, body weight after a
short treatment period. However, these effects were largely reversed by the
cessation of dapagliflozin, suggesting that this agent should be administered
continuously to maintain clinical usefulness in overweight patients with type 2
diabetes.
PMID- 28426261
TI - A morphological study of uterine alterations in mice due to exposure to cadmium.
AB - We investigated the morphologic and molecular effects of exposure to cadmium (Cd)
for 30 and 60 days on the uteri of mice. We assessed uterine morphometric
measurements, eosinophilia, mast cell numbers, endometrial apoptosis,
proliferation and estrogen receptor alpha (ERalpha) immunoreactivity. We examined
vaginal smears that reflected the hormonal alterations in the female reproductive
tract. Because the female reproductive tract exhibits different morphology at
each stage of the estrous cycle, we sacrificed all animals at estrus to make
appropriate comparisons. Female BALB/c mice were exposed to 200 ppm Cd in their
drinking water for either 30 or 60 days. Cd exposure caused significant decreases
in endometrial thickness and number of glands in estrus phase uteri. The
endometrial eosinophilia in the groups exposed to Cd also decreased compared to
controls. Cd exposure increased the number of mast cells. Luminal and glandular
epithelia were examined using the terminal deoxynucleotidyl transferase dUTP nick
end labeling (TUNEL) assay and by immunostaining proliferating cell nuclear
antigen (PCNA) and estrogen receptor alpha (ERalpha). Compared to controls, the
apoptotic index increased with time in both Cd exposed groups, while the
proliferation index decreased. ERalpha immunoreactivity was decreased in both Cd
exposed groups compared to controls; the decrease was most apparent in the 30 day
Cd group. We found that 60 day Cd exposure increased apoptosis in the
endometrium, which may affect the receptivity of the uterus for implantation.
PMID- 28426262
TI - Feasibility of outpatient total hip and knee arthroplasty in unselected patients.
AB - Background and purpose - The number of patients who are suitable for outpatient
total hip and knee arthroplasty (THA and TKA) in an unselected patient population
remains unknown. The purpose of this prospective 2-center study was to identify
the number of patients suitable for outpatient THA and TKA in an unselected
patient population, to investigate the proportion of patients who were discharged
on the day of surgery (DOS), and to identify reasons for not being discharged on
the DOS. Patients and methods - All consecutive, unselected patients who were
referred to 2 participating centers and who were scheduled for primary THA and
TKA were screened for eligibility for outpatient surgery with discharge to home
on DOS. If patients did not fulfill the discharge criteria, the reasons
preventing discharge were noted. Odds factors with relative risk intervals for
not being discharged on DOS were identified while adjusting for age, sex, ASA
score, BMI and distance to home. Results - Of the 557 patients who were referred
to the participating surgeons during the study period, 54% were potentially
eligible for outpatient surgery. Actual DOS discharge occurred in 13-15% of the
557 patients. Female sex and surgery late in the day increased the odds of not
being discharged on the DOS. Interpretation - This study shows that even in
unselected THA and TKA patients, same-day discharge is feasible in about 15% of
patients. Future studies should evaluate safety aspects and economic benefits.
PMID- 28426263
TI - Using Contingent Reinforcement to Augment Muscle Activation After Perinatal
Brachial Plexus Injury: A Pilot Study.
AB - AIM: Examine the feasibility of increasing muscle activation with
electromyographically (EMG)-triggered musical-video as reinforcement for children
with perinatal brachial plexus injury (PBPI). METHODS: Six children with PBPI
(9.3 +/- 6.3 months; 5 female, 1 male) and 13 typically developing (TD) controls
(7.8 +/- 3.5 months; 4 female, 9 males) participated. The left arm was affected
in 5/6 children with PBPI. We recorded the integral (Vs) of biceps activation
with surface EMG during two conditions per arm in one session: (1) 100 second (s)
baseline without reinforcement and (2) 300 s reinforcement (musical-video
triggered to play with biceps activation above threshold [V]). We examined the
relation between the mean integral with reinforcement and hand preference.
RESULTS: Mean biceps activation significantly increased from baseline in the
affected arm of the group with PBPI by the 2nd (p < .008) and 3rd (p < .0004) 100
s intervals of reinforcement. Six of 6 children with PBPI and 12/13 TD controls
increased activation in at least one arm. A lower integral was linked with hand
preference for the unaffected right side in the PBPI group. CONCLUSION: This
study supports contingent reinforcement as a feasible method to increase muscle
activation. Future work will examine training dose and intensity to increase arm
function.
PMID- 28426264
TI - Differences between treatment-seeking and non-treatment-seeking participants in
medication studies for alcoholism: do they matter?
AB - BACKGROUND: Medication development for alcoholism typically includes experimental
pharmacology studies with non-treatment-seeking individuals with alcohol use
disorder (AUD) paving the way for randomized controlled trials in treatment
seekers with AUD. OBJECTIVES: The goal of this study is to provide a direct
comparison between AUD treatment-seeking research participants and non-treatment
seeking participants on demographic and clinical variables and to test whether
variables that differentiate the two groups are associated with clinical
outcomes. METHOD: Non-treatment-seeking AUD participants (n = 213; 76.3% male)
who completed behavioral pharmacology studies were compared to treatment-seekers
who completed the COMBINE Study (n = 1383; 69.1% male) on demographic and
clinical variables. Analyses examined whether the variables that differentiated
the two groups predicted treatment outcomes in the COMBINE Study. RESULTS:
Analyses revealed that treatment-seeking participants were older, had more years
of education, higher Alcohol Dependence Scale scores, higher Drinker Inventory of
Consequences scores, higher Obsessive Compulsive Drinking Scale scores, a greater
number of DSM-IV symptoms of AUD, longer duration of AUD, and consumed more
standard drinks and more drinks per drinking day (i.e., in the past 30 days)
compared to non-treatment-seeking participants. Nearly all characteristics that
differed between the groups predicted at least one of the primary clinical
outcomes of the COMBINE Study. CONCLUSIONS: This study highlights a host of
clinical and demographic factors that differ between non-treatment-seeking and
treatment-seeking research participants and the clinical significance of these
variables. Differences between samples should be considered and addressed in
order to promote greater consilience across stages of medication development.
PMID- 28426265
TI - Transdermal iontophoresis patch with reverse electrodialysis.
AB - Reverse electrodialysis (RED) technology generates energy from the salinity
gradient by contacting waters with different salinity. Herein, we develop the
disposable skin patch using this eco-friendly energy. The current density, which
can be controlled easily without special circuit, is enough to iontophoretic drug
delivery. In vitro study, this iontophoretic system enhanced the transdermal
delivery of peptide, which is difficult to penetrate the skin barrier by simple
diffusion. We design the disposable iontophoretic skin patch using RED system and
suggest this patch can be apply on new cosmetic patch or disposable drug patch.
PMID- 28426266
TI - Physicochemical Characteristics of the Seed and Seed Oil of the Potentially
Medicinal Plant Ziziphus oenoplia.
AB - The proximate composition of seeds, physicochemical characteristics, and fatty
acid profiles of Ziziphus oenoplia seed oil were determined in this study. The
seeds possessed low moisture (4.54%) and high carbohydrate (42.96%) and protein
content (40%), making the seed oil suitable for storage and consumption. The
saponification value (197.80) of the seed oil makes it a promising source for the
soap and shampoo industry. The iodine and saponification values are comparable to
those of major edible seed oils such as groundnut and soybean. The high amount of
monounsaturated fatty acids (53.41%), especially oleic acid (53.38%), present in
the oil makes it a better source for a low-fat diet and may reduce the risk of
various heart-related diseases.
PMID- 28426267
TI - A Phase-2 Trial of Single Agent Axitinib as Maintenance Therapy Following First
Line Treatment With Modified FOLFOX/Bevacizumab in Patients With Metastatic
Colorectal Cancer.
AB - This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for
patients with metastatic colorectal cancer (mCRC) following first-line treatment
with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed
by axitinib maintenance after four cycles. The primary endpoint was progression
free survival (PFS). Seventy patients were enrolled. Common treatment-related
toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during
FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral
neuropathy during axitinib treatment. Median PFS was 8.3 months. Treatment with
FOLFOX/bevacizumab followed by maintenance axitinib as first-line treatment for
mCRC produced a median PFS consistent with historical controls of other first
line regimens.
PMID- 28426268
TI - Putative Biomarkers of Response to Treatment in Breast Cancer Patients: A Pilot
Assay.
AB - Identifying tumor biomarkers associated with clinical behavior in breast cancer
patients may allow higher accuracy in the selection of treatment. Different types
of cells were determined in the primary tumors of stage I, II, and III of breast
cancer patients, who were assigned to one of the two groups: (1) disease-free or
(2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor
samples. CD4+ lymphocytes and CD44+CD24-/low cells (cancer stem cells) showed a
significant association with clinical outcome at 5 years of primary treatment,
while CD8+, Foxp3+, CD34+, and myeloid-derived suppressor cells did not show any
association. Coincident with the results of individual analysis, we identified
CD4+ cells and CD44+CD24-/low cells as good predictors of long-term clinical
outcome in a logistic regression.
PMID- 28426269
TI - 2016 International Orthoptic Congress Burian Lecture: Folklore or Evidence?
AB - The theme of the 2016 Burian Lecture is how our understanding of strabismus has
been changed by the research carried out in our laboratory in Reading over the
years. Accommodation and convergence are fundamental to orthoptics, but actual
responses have often been very different compared to what we had expected. This
paper outlines how our laboratory's understanding of common issues such as normal
development of accommodation and convergence, their linkage, intermittent
strabismus, anisometropia, orthoptic exercises, and risk factors for strabismus
have changed. A new model of thinking about convergence and accommodation may
help us to better understand and predict responses in our patients.
PMID- 28426270
TI - The Successful Treatment of Primary Cutaneous Localized Amyloidosis with a
Combined Therapy of Ablative Fractionated CO2 Laser,Topical Retinoid,
Corticosteroids and Levovitamin C: Five Cases with a Two-Year Follow Up.
PMID- 28426271
TI - Factors Associated with the Efficacy of Trigger Point Injection in Advanced
Cancer Patients.
AB - BACKGROUND: Few studies have reported the efficacy of trigger point injection
(TPI) to myofascial trigger points (MTrPs) in advanced cancer patients. Factors
that are associated with TPI efficacy have not yet been elucidated. OBJECTIVE:
The study was aimed at evaluating factors that are associated with TPI efficacy
to MTrPs in advanced cancer patients. DESIGN: Factors that are associated with
TPI efficacy were retrospectively identified based on a comparison between
clinically relevant responders and nonresponders by using multivariate regression
analysis. SETTING/SUBJECTS: One hundred five advanced cancer patients who visited
the Palliative Care Department with a chief complaint of pain and who received
TPI treatment to the MTrP at the pain site. RESULTS: The TPI efficacy rate on the
day after TPI treatment was 0.59 (95% confidence interval [CI]: 0.50-0.68).
Significant factors associated with TPI efficacy were coexistence of cancer pain
with MTrP at the pain site (odds ratio [OR]: 3.87, 95% CI: 1.21-12.4), MTrP at
areas other than lower back or hip (OR: 6.45, 95% CI: 1.98-21.0), and fewer MTrPs
(OR: 0.64, 95% CI: 0.42-0.99). Coexistence of cancer pain at the pain site of the
chief complaint was observed in 64% of study subjects (95% CI: 0.55-0.73).
CONCLUSIONS: The TPI efficacy is likely high when advanced cancer patients have
fewer MTrPs together with cancer pain at areas other than the lower back or hip.
MTrPs in advanced cancer patients are more commonly observed together with cancer
pain rather than independently. Healthcare providers should recognize the
relationship between MTrP and cancer pain and proactively perform physical
examinations to detect MTrPs for potential TPI.
PMID- 28426272
TI - Temperature-dependent regulation of rDNA condensation in Saccharomyces
cerevisiae.
AB - Chromatin condensation during mitosis produces detangled and discrete DNA
entities required for high fidelity sister chromatid segregation during mitosis
and positions DNA away from the cleavage furrow during cytokinesis. Regional
condensation during G1 also establishes a nuclear architecture through which gene
transcription is regulated but remains plastic so that cells can respond to
changes in nutrient levels, temperature and signaling molecules. To date,
however, the potential impact of this plasticity on mitotic chromosome
condensation remains unknown. Here, we report results obtained from a new
condensation assay that wildtype budding yeast cells exhibit dramatic changes in
rDNA conformation in response to temperature. rDNA hypercondenses in wildtype
cells maintained at 37 degrees C, compared with cells maintained at 23 degrees C.
This hypercondensation machinery can be activated during preanaphase but readily
inactivated upon exposure to lower temperatures. Extended mitotic arrest at 23
degrees C does not result in hypercondensation, negating a kinetic-based argument
in which condensation that typically proceeds slowly is accelerated when cells
are placed at 37 degrees C. Neither elevated recombination nor reduced
transcription appear to promote this hypercondensation. This heretofore
undetected temperature-dependent hypercondensation pathway impacts current views
of chromatin structure based on conditional mutant gene analyses and
significantly extends our understanding of physiologic changes in chromatin
architecture in response to hypothermia.
PMID- 28426273
TI - Preclinical development of BCG.HIVA2auxo.int, harboring an integrative expression
vector, for a HIV-TB Pediatric vaccine. Enhancement of stability and specific HIV
1 T-cell immunity.
AB - One of the critical issues that should be addressed in the development of a BCG
based HIV vaccine is genetic plasmid stability. Therefore, to address this issue
we have considered using integrative vectors and the auxotrophic mutant of BCG
complemented with a plasmid carrying a wild-type complementing gene. In this
study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid,
p2auxo.HIVAint, expressing the HIV-1 clade A immunogen HIVA. This shuttle vector
uses an antibiotic resistance-free mechanism for plasmid selection and
maintenance. It was first transformed into a glycine auxotrophic E. coli strain
and subsequently transformed into a lysine auxotrophic Mycobacterium bovis BCG
strain to generate the vaccine BCG.HIVA2auxo.int. Presence of the HIVA gene
sequence and protein expression was confirmed. We demonstrated that the in vitro
stability of the integrative plasmid p2auxo.HIVAint was increased 4-fold, as
compared with the BCG strain harboring the episomal plasmid, and was genetically
and phenotypically characterized. The BCG.HIVA2auxo.int vaccine in combination
with modified vaccinia virus Ankara (MVA).HIVA was found to be safe and induced
HIV-1 and Mycobacterium tuberculosis-specific interferon-gamma-producing T-cell
responses in adult BALB/c mice. We have engineered a more stable and immunogenic
BCG-vectored vaccine using the prototype immunogen HIVA. Thus, the use of
integrative expression vectors and the antibiotic-free plasmid selection system
based on "double" auxotrophic complementation are likely to improve the
mycobacterial vaccine stability in vivo and immunogenicity to develop not only
recombinant BCG-based vaccines expressing second generation of HIV-1 immunogens
but also other major pediatric pathogens to prime protective responses shortly
following birth.
PMID- 28426274
TI - A critical appraisal of 'Shingrix', a novel herpes zoster subunit vaccine (HZ/Su
or GSK1437173A) for varicella zoster virus.
AB - HZ/Su, branded as 'Shingrix', is one of the newest vaccines to be submitted for
multi-national regulatory approval. It is targeted to prevent shingles, a global
concern with aging populations. A live attenuated vaccine for shingles has been
available for over a decade, however it is contraindicated in specific subgroups
of people, and there are added concerns regarding long-term immunogenicity. HZ/Su
is the first subunit vaccine developed to protect against shingles. This paper
provides a critical appraisal of current evidence regarding HZ/Su.
PMID- 28426275
TI - Size does matter!
PMID- 28426276
TI - Integrative epigenetic and genetic pan-cancer somatic alteration portraits.
AB - Genetic and epigenetic alterations are required for carcinogenesis and the
mutation burden across tumor types has been investigated. Here, we investigate
epigenetic alterations with a novel measure of global DNA methylation
dysregulation, the methylation dysregulation index (MDI), across 14 cancer types
in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using
Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the
MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701)
from each tumor site. Copy number alteration, and mutation burden were retrieved
from cBioportal (n = 5,152). We tested the relation of subject MDI across tumors
and with age, gender, tumor stage, estimated tumor purity, and copy number
alterations for both overall MDI and genomic-context-specific MDI. We also
investigated the top most dysregulated loci shared across tumor types. There was
a broad range of extent in methylation dysregulation across tumor types (P < 2.2E
16). However, a consistent pattern of methylation dysregulation stratified by
genomic context was observed across tumor types where the highest dysregulation
occurred at non-CpG island regions. Considering other summary measures of somatic
alteration, MDI was correlated with copy number alterations but not with mutation
burden. Using the top dysregulated CpG sites in common across tumors, 4 classes
of cancer types were observed, and the functional consequences of these
alterations to gene expression were confirmed. This work identified the global
DNA methylation dysregulation patterns across 14 cancer types showing a higher
impact for the non-CpG island areas. The most dysregulated loci across cancer
types identified common clusters across cancer types that may have implications
for future treatment and prevention measures.
PMID- 28426277
TI - Topical Ganciclovir in Cytomegalovirus Anterior Uveitis.
AB - PURPOSE: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus
(CMV) anterior uveitis in a tertiary uveitis referral center in Brussels,
Belgium. METHODS: A retrospective study of patients with a clinical diagnosis of
CMV anterior uveitis/endotheliitis demonstrated by a positive polymerase chain
reaction and/or Goldmann-Witmer coefficient (GWc). RESULTS: We report a series of
15 patients presenting clinical characteristics of CMV anterior uveitis. Patients
had a pretreatment follow-up of 13.00 +/- 12.78 months and a posttreatment follow
up of 42.64 +/- 31.23 months. The 14 non-Asian patients (93.3%) had clinical
characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%)
had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation,
uveitis was unilateral in all patients, visual acuity (VA) was 0.91 +/- 0.25, and
all patients had an increased intraocular pressure (IOP), with a mean IOP of
41.40 +/- 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had
glaucoma, 2 needed glaucoma surgery (13.3%). The mean final VA was 0.93 +/- 0.11;
13 patients (86.5%) reached a final VA of 0.7 to 1. Patients had a significantly
lower number of recurrences/year posttreatment (0.76 +/- 0.57) than in the
pretreatment period (3.76 +/- 2.44) (P = 0.001). The mean time to recurrence
increased from 4.03 months before treatment to 12.58 months after treatment (P =
0.003). CONCLUSION: Our results suggest that patients treated with 0.15% topical
ganciclovir have a decreased frequency of CMV anterior uveitis recurrences, most
preserve a relatively good central vision over time. However, glaucoma is a
frequent and severe complication.
PMID- 28426278
TI - HOP3 a new regulator of the ER stress response in Arabidopsis with possible
implications in plant development and response to biotic and abiotic stresses.
AB - HOPs (heat shock protein 70 (HSP70)-heat shock protein 90 (HSP90) organizing
proteins) are a highly conserved family of cytosolic cochaperones. In a recent
study we showed that HOP3, a member of the HOP family in Arabidopsis, plays an
essential role during endoplasmic reticulum (ER) stress in plants. Interestingly,
we also demonstrated that AtHOP3 interacts with binding immunoglobulin protein
(BiP), a major ER-resident chaperone. All these data suggest that HOP3 could
assist BiP in protein folding in the ER. These findings open the exciting
possibility that HOP3, through its role in the alleviation of ER stress, could
play an important function during different developmental processes and in
response to different biotic and abiotic stresses.
PMID- 28426279
TI - Combination of gemcitabine and docetaxel regresses both gastric leiomyosarcoma
proliferation and invasion in an imageable patient-derived orthotopic xenograft
(iPDOX) model.
AB - Gastric leiomyosarcoma is a recalcitrant cancer and the chemotherapy strategy is
controversial. The present study used a patient-derived orthotopic xenograft
(PDOX) nude mouse model of gastric leiomyosarcoma to identify an effective
therapeutic regimen to develop individualized precision medicine for this
disease. The gastric leiomyosarcoma obtained from a patient was first grown in
transgenic nude mice ubiquitously expressing red fluorescent protein (RFP) to
stably label the tumor stroma. The RFP-expressing tumor was then passaged
orthotopically in the gastric wall of non-transgenic nude mice to establish an
imageable PDOX (iPDOX) model. The bright fluorescent tumor was readily imaged
over time to determine drug efficacy. Four weeks after implantation, 70 PDOX nude
mice were divided into 7 groups: control without treatment (n = 10); doxorubicin
(DOX) (2.4 mg/kg, intraperitoneally (i.p.), once a week for 2 weeks, n = 10);
gemcitabine (GEM)/ docetaxel (DOC) (GEM: 100 mg/kg, DOC: 20 mg/kg, i.p., once a
week for 2 weeks, n = 10); cyclophosphamide (CPA) (140 mg/kg, i.p., once a week
for 2 weeks, n = 10); temozolomide (TEM) (25 mg/kg, orally, daily for 14
consecutive days, n = 10); yondelis (YON) (0.15 mg/kg, i.v., once a week for 2
weeks, n = 10); pazopanib (PAZ) (100 mg/kg, orally, daily for 14 consecutive
days, n = 10). On day 14 from initiation of treatment, all treatments except PAZ
significantly inhibited tumor growth compared with untreated control (DOX: p <
0.01, GEM/DOC: p < 0.01, CPA: p < 0.01, TEM: p < 0.01, YON: p < 0.01) on day 14
after initiation. In addition, only GEM/DOC was more significantly effective than
DOX (p < 0.05). GEM/DOC could regress the leimyosarcoma in the PDOX model and has
important clinical potential for precision individual treatment of leiomyosarcoma
patients.
PMID- 28426280
TI - Alternative plant host defense against transposon activities occurs at the post
translational stage.
AB - The Antirrhinum DNA transposon Tam3 uniquely demonstrates low temperature
dependent transposition (LTDT), so transposition does not occur at high
temperatures. We previously showed that the detainment of Tam3 transposase
(TPase) at the plasma membrane occurs when transposition is inactive, and that
TPase is released at the permissive state of Tam3 transposition. LTDT of Tam3 is
attributed to interactions between Tam3 and its host. In this addendum, we
propose a model to explain the LTDT of Tam3, which is regarded as an equilibrium
state reached between the host and parasite to maximize the fitness of both.
PMID- 28426281
TI - Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in
porcine embryonic fibroblasts.
AB - Previous research has shown that a subpopulation of cells within cultured human
dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse)
cells, are preferentially reprogrammed into induced pluripotent stem cells.
However, controversy exists over whether these cells are the only cells capable
of being reprogrammed from a heterogeneous population of fibroblasts. Similarly,
there is little research to suggest such cells may exist in embryonic tissues or
other species. To address if such a cell population exists in pigs, we
investigated porcine embryonic fibroblast populations (pEFs) and identified
heterogeneous expression of several key cell surface markers. Strikingly, we
discovered a small population of stage-specific embryonic antigen 1 positive
cells (SSEA-1+) in Danish Landrace and Gottingen minipig pEFs, which were absent
in the Yucatan pEFs. Furthermore, reprogramming of SSEA-1+ sorted pEFs led to
higher reprogramming efficiency. Subsequent transcriptome profiling of the SSEA
1+ vs. the SSEA-1neg cell fraction revealed highly comparable gene signatures.
However several genes that were found to be upregulated in the SSEA-1+ cells were
similarly expressed in mesenchymal stem cells (MSCs). We therefore termed these
cells SSEA-1 Expressing Enhanced Reprogramming (SEER) cells. Interestingly, SEER
cells were more effective at differentiating into osteocytes and chondrocytes in
vitro. We conclude that SEER cells are more amenable for reprogramming and that
the expression of mesenchymal stem cell genes is advantageous in the
reprogramming process. This data provides evidence supporting the elite theory
and helps to delineate which cell types and specific genes are important for
reprogramming in the pig.
PMID- 28426284
TI - Participatory Genomic Research: Ethical Issues from the Bottom Up to the Top
Down.
AB - Participatory approaches to genomic research manifest along a continuum from
bottom-up citizen-science initiatives designed to liberate scientific inquiry
from the constraints of traditional research institutional contexts and
professional practices to top-down investigator-initiated studies designed to
expose the public to scientific research processes and build its support and
enthusiasm for genomic research. With foundations as varied as open science,
crowdsourcing, patient advocacy, social media, the digitization of health, and
the neoliberalization of academic research, a range of ethical frameworks inform
the modes of participatory genomic research. Using illustrations from citizen
genomic science, patient advocacy, and investigator-led and government-initiated
genomic research efforts, we argue that as participatory genomic research pushes
the conventional research boundaries toward a more democratizing ethos, it
challenges scientific practices and the ethical conduct of genomic research both
within and outside of the traditional sites of biomedical innovation.
PMID- 28426282
TI - Emerging roles of macrosatellite repeats in genome organization and disease
development.
AB - Abundant repetitive DNA sequences are an enigmatic part of the human genome.
Despite increasing evidence on the functionality of DNA repeats, their biologic
role is still elusive and under frequent debate. Macrosatellites are the largest
of the tandem DNA repeats, located on one or multiple chromosomes. The
contribution of macrosatellites to genome regulation and human health was
demonstrated for the D4Z4 macrosatellite repeat array on chromosome 4q35. Reduced
copy number of D4Z4 repeats is associated with local euchromatinization and the
onset of facioscapulohumeral muscular dystrophy. Although the role other
macrosatellite families may play remains rather obscure, their diverse
functionalities within the genome are being gradually revealed. In this review,
we will outline structural and functional features of coding and noncoding
macrosatellite repeats, and highlight recent findings that bring these sequences
into the spotlight of genome organization and disease development.
PMID- 28426283
TI - Identification of the proteome complement of humanTLK1 reveals it binds and
phosphorylates NEK1 regulating its activity.
AB - The Tousled Like kinases (TLKs) are involved in numerous cellular functions,
including the DNA Damage Response (DDR), but only a handful of substrates have
been identified thus far. Through a novel proteomic screen, we have now
identified 165 human proteins interacting with TLK1, and we have focused this
work on NEK1 because of its known role in the DDR, upstream of ATR and Chk1. TLK1
and NEK1 were found to interact by coIP, and their binding is strengthened
following exposure of cells to H2O2. Following incubation with doxorubicin, TLK1
and NEK1 relocalize with nuclear repair foci along with gammaH2AX. TLK1
phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an
increase in its activity. Following DNA damage, addition of the TLK1 inhibitor,
THD, or overexpression of NEK1-T141A mutant impaired ATR and Chk1 activation,
indicating the existence of a TLK1>NEK1>ATR>Chk1 pathway. Indeed, overexpression
of the NEK1-T141A mutant resulted in an altered cell cycle response after
exposure of cells to oxidative stress, including bypass of G1 arrest and
implementation of an intra S-phase checkpoint.
PMID- 28426285
TI - The Yin and Yang of Autism Genetics: How Rare De Novo and Common Variations
Affect Liability.
AB - The etiology of autism spectrum disorder (ASD) is complex, involving both genetic
and environmental contributions to individual and population-level liability.
Early researchers hypothesized that ASD arises from polygenic inheritance, but
later results, such as the identification of mutations in certain genes that are
responsible for syndromes associated with ASD, led others to propose that de novo
mutations of major effect would account for most cases. This yin and yang of
monogenic causes and polygenic inheritance continues to this day. The development
of genome-wide genotyping and sequencing techniques has resulted in remarkable
advances in our understanding of the genetic architecture of risk for ASD. The
combined research findings provide solid evidence that ASD is a complex polygenic
disorder. Rare de novo and inherited variations act within the context of a
common-variant genetic load, and this load accounts for the largest portion of
ASD liability.
PMID- 28426286
TI - On the Evolution of Lactase Persistence in Humans.
AB - Lactase persistence-the ability of adults to digest the lactose in milk-varies
widely in frequency across human populations. This trait represents an adaptation
to the domestication of dairying animals and the subsequent consumption of their
milk. Five variants are currently known to underlie this phenotype, which is
monogenic in Eurasia but mostly polygenic in Africa. Despite being a textbook
example of regulatory convergent evolution and gene-culture coevolution, the
story of lactase persistence is far from clear: Why are lactase persistence
frequencies low in Central Asian herders but high in some African hunter
gatherers? Why was lactase persistence strongly selected for even though milk
processing can reduce the amount of lactose? Are there other factors, outside of
an advantage of caloric intake, that contributed to the selective pressure for
lactase persistence? It is time to revisit what we know and still do not know
about lactase persistence in humans.
PMID- 28426287
TI - Pregnancy and the Acceptability of Computer-Based Versus Traditional Mental
Health Treatments.
AB - BACKGROUND: Recent recommendations urge increased depression screening in
pregnant and postpartum women, potentially increasing demand for treatment.
Computer-based psychotherapy treatments may address some of perinatal women's
unique mental health treatment needs and barriers. MATERIALS AND METHODS: We
conducted a quantitative survey of pregnant women (>=12 weeks of gestation) on
preferences regarding computer-based therapies compared with traditional
therapies (psychotherapy and medication). Nonpregnant women and men served as
comparison groups. Participants were provided descriptions of three computer
based therapies: video telehealth therapy (VTT), computer-assisted therapy (CAT),
and self-guided online therapy (SGO). Participants were asked to select all
options that they would consider for treatment as well as first choice
preference. The Patient Health Questionnaire-9 (PHQ-9) assessed current
depressive symptomatology, and the Mini International Neuropsychiatric Interview
(MINI) assessed psychiatric history. RESULTS: Participants included pregnant
females (n = 111), nonpregnant females (n = 147), and males (n = 54). Among
pregnant women, 77.5% (n = 86) indicated that they would consider some form of
computer-based therapy for mental health treatment during pregnancy; VTT was the
most commonly considered, followed by CAT and SGO. When asked to select their
preferred intervention, traditional talk therapy was the first choice among all
three groups, controlling for treatment history and PHQ-9 score. About one-third
of pregnant women chose some form of computer-based therapy as their top choice.
CONCLUSIONS: While computer-based therapies were acceptable to most pregnant
women in this sample, traditional talk therapy was the preferred option. Future
research should consider how to tailor computer-based therapies to the unique
needs of perinatal women.
PMID- 28426288
TI - Post translational modifications of Rab GTPases.
AB - Rab GTPases, the highly conserved members of Ras GTPase superfamily are central
players in the vesicular trafficking. They are critically involved in
intracellular trafficking pathway, beginning from formation of vesicles on donor
membranes, defining trafficking specificity to facilitating vesicle docking on
target membranes. Given the dynamic roles of Rabs during different stages of
vesicular trafficking, mechanisms for their spatial and temporal regulation are
crucial for normal cellular function. Regulation of Rab GTPase activity,
localization and function has always been focused in and around the association
of GDP dissociation inhibitor (GDI), Guanine nucleotide Exchange Factor (GEFs)
and GTPase accelerating protein (GAP) to Rabs. However, several recent studies
have highlighted the importance of different post-translational modifications in
regulation of Rab activation and function. This review provides a summary of
various post translational modifications (PTMs) and their significance to
regulate localization and function of different Rabs.
PMID- 28426289
TI - Injuries and exposures among ocean safety providers: A review of workplace
injuries and exposures from 2007-2012.
AB - Research on workplace injuries and exposures in ocean safety personnel remains
limited. Despite increasing beach attendance and reliance on lifeguards for
protection, the most common types of injuries, equipment resulting in injuries,
and environmental exposures remains unknown. This study reviewed OSHA 300 logs
summarizing workers' compensation claims from 2007-2012 to identify common body
parts injured, action at time of injury, equipment causing injury, and
environmental exposures. A secondary phase consisted of a cross-sectional
anonymous survey to determine demographics, body part injured, equipment causing
injury, sun and environmental exposures, action at time of injury, and proportion
of injuries reported to the department. During the 6-year period, 304 claims from
the OSHA logs were reviewed, finding the lower extremity was most commonly
injured with 2921 (31.9%) cumulative lost work days (104 reported injured, 34.2%)
followed by the back with 1679 (18.4%) lost work days (39 reported injuries,
12.8%). Of the 304 occupational injury claims from OSHA logs, 108 incidents
(35.5%) occurred during rescues, 87 (28.6%) during normal duties, and 31 (10.2%)
during training. Of survey participants, 22/52 sustained an injury, with 14
filling a worker's compensation claim. The rescueboard resulted in 7/22 injuries
(31.8%) while 17 (32.7%) of respondents sought care for a sun related concern
with a mean of 9.3 days lost. Occupational injuries in ocean safety personnel are
largely unknown. In this study, lower extremity and back injuries were the most
common musculoskeletal injuries providers encountered. Rescues and moving
equipment were common actions at the time of injury. With this preliminary
information, jurisdictions may develop training directed at rescue techniques and
safer options for moving heavy equipment.
PMID- 28426290
TI - Development of a thoracic personal sampler system for co-sampling of sulfuric
acid mist and sulfur dioxide gas.
AB - A novel personal sampler was designed to measure inorganic acid mists and gases
for determining human exposure levels to these acids in workplaces. This sampler
consists of (1) a parallel impactor for classifying aerosol by size following the
ISO/CEN/ACGIH defined human thoracic fraction, (2) a cellulose filter to collect
the residual acid mist but allowing penetration of sulfur dioxide gas, and (3) an
accordion-shaped porous membrane denuder (aPMD) for adsorbing the penetrating
sulfur dioxide gas. Acid-resistant PTFE was chosen as the housing material to
minimize sampling interference. To test the performance of the parallel impactor,
monodisperse aerosol was created by a vibrating orifice aerosol generator. The
results showed that the penetration curve of the impactor run at 2 LPM flow rate
agreed well with the defined thoracic fraction. Almost all sampling biases were
within 10% for particle size distributions with MMAD between 1-25 um and GSD
between 1.75-4, which meets the criteria of the EN 13205 standard. To evaluate
the performance of the aPMDs, sulfur dioxide gas was sourced directly from a
cylinder. The aPMDs maintained a gas collection efficiency greater than 95% for 4
hr when sampling 8.6 ppm of sulfur dioxide gas. While the aPMD had similar
performance to the commonly adopted annular or honeycomb denuders made of glass,
this shatterproof aPMD is only half of the volume and 1/25th the weight of the
honeycomb denuder. Testing of the entire sampler with a mixture of sulfuric acid
mist and sulfur dioxide gas showed the system could sample both with negligible
interference. All the test results illustrate that the new sampler, which is
flat, lightweight, and portable, is suitable for personal use and is capable of a
more accurate assessment of human exposure to inorganic acid mist and SO2 gas.
PMID- 28426291
TI - The Structure of Policy Networks for Injury and Violence Prevention in 15 US
Cities.
AB - OBJECTIVES: Changes in policy can reduce violence and injury; however, little is
known about how partnerships among organizations influence policy development,
adoption, and implementation. To understand partnerships among organizations
working on injury and violence prevention (IVP) policy, we examined IVP policy
networks in 15 large US cities. METHODS: In summer 2014, we recruited 15 local
health departments (LHDs) to participate in the study. They identified an average
of 28.9 local partners (SD = 10.2) working on IVP policy. In late 2014, we sent
survey questionnaires to 434 organizations, including the 15 LHDs and their local
partners, about their partnerships and the importance of each organization to
local IVP policy efforts; 319 participated. We used network methods to examine
the composition and structure of the policy networks. RESULTS: Each IVP policy
network included the LHD and an average of 21.3 (SD = 6.9) local partners. On
average, nonprofit organizations constituted 50.7% of networks, followed by
government agencies (26.3%), schools and universities (11.8%), coalitions
(11.2%), voluntary organizations (9.6%), hospitals (8.5%), foundations (2.2%),
and for-profit organizations (0.7%). Government agencies were perceived as
important by the highest proportion of partners. Perceived importance was
significantly associated with forming partnerships in most networks; odds ratios
ranged from 1.07 (95% CI, 1.02-1.13) to 2.35 (95% CI, 1.68-3.28). Organization
type was significantly associated with partnership formation in most networks
after controlling for an organization's importance to the network. CONCLUSIONS:
Several strategies could strengthen local IVP policy networks, including (1)
developing connections with partners from sectors that are not well integrated
into the networks and (2) encouraging indirect or less formal connections with
important but missing partners and partner types.
PMID- 28426292
TI - Efficacy of Three Different Lasers on Eradication of Enterococcus faecalis and
Candida albicans Biofilms in Root Canal System.
AB - OBJECTIVE: The objective was to compare the efficacy of three different lasers in
disinfection of root canals inoculated with Enterococcus faecalis and Candida
albicans biofilms. BACKGROUND: Endodontic space disinfection depends on the type
of root canal irrigant used and the way it is delivered and agitated because
irrigants have limited ability to reach all parts of root canal system. MATERIALS
AND METHODS: Thirty single-rooted human teeth were selected. Root canals were
instrumented and root surfaces were sealed using adhesive and the apical openings
with adhesive and composite resin. Roots were fixed in Eppendorf tubes and
sterilized in autoclave. The specimens were randomly divided into three
experimental groups (n = 10) and inoculated with E. faecalis and C. albicans.
After 7 days of incubation period, the number of E. faecalis and C. albicans
colony-forming units (CFUs) was determined for each root canal. In the first
experimental group, Er:YAG laser (0.3 W) with photon-induced photoacoustic
streaming technique was used for root canal disinfection, in the second, Nd:YAG
laser (1.5 W), and in the third, Er,Cr:YSGG (1.25 W) laser was used. After
different root canal disinfection protocols, the number of E. faecalis and C.
albicans CFUs was determined again for each root canal. RESULTS: Er:YAG and
Er,Cr:YSGG lasers eradicated significant number of E. faecalis and C. albicans
CFUs (p < 0.05), while Nd:YAG laser irradiation did not result in statistically
significant reduction (p > 0.05). Er,Cr:YSGG laser eradicated significantly more
microorganisms in comparison with Er:YAG laser (p < 0.05). CONCLUSIONS:
Er,Cr:YSGG laser was the most efficient tool in eradication of E. faecalis and C.
albicans biofilms.
PMID- 28426293
TI - Identifying thermal breakdown products of thermoplastics.
AB - Polymers processed to produce plastic articles are subjected to temperatures
between 150 degrees C and 450 degrees C or more during overheated processing and
breakdowns. Heat-based processing of this nature can lead to emission of volatile
organic compounds (VOCs) into the thermoplastic processing shop. In this study,
laboratory experiments, qualitative and quantitative emissions measurement in
thermoplastic factories were carried out. The first step was to identify the
compounds released depending on the thermoplastic nature, the temperature and the
type of process. Then a thermal degradation protocol that can extrapolate the
laboratory results to industry scenarios was developed. The influence of three
parameters on released thermal breakdown products was studied: the sample
preparation methods-manual cutting, ambient, or cold grinding-the heating rate
during thermal degradation-5, 10 20, and 50 degrees C/min-and the decomposition
method-thermogravimetric analysis and pyrolysis. Laboratory results were compared
to atmospheric measurements taken at 13 companies to validate the protocol and
thereby ensure its representativeness of industrial thermal processing. This
protocol was applied to most commonly used thermoplastics to determine their
thermal breakdown products and their thermal behaviour. Emissions data collected
by personal exposure monitoring and sampling at the process emission area show
airborne concentrations of detected compounds to be in the range of 0-3 mg/m3
under normal operating conditions. Laser cutting or purging operations generate
higher pollution levels in particular formaldehyde which was found in some cases
at a concentration above the workplace exposure limit.
PMID- 28426294
TI - The Interface Among Poverty, Air Mattress Industry Trends, Policy, and Infant
Safety.
AB - Infants can suffocate on air mattresses, even when the mattress is fully
inflated. The interfacing issues of poverty, the bedbug epidemic, and changes in
the design and marketing of air mattresses may be increasing consumer use of air
mattresses as primary sleep environments and thus increasing the potential for
infant death. Despite recent changes to improve air mattress safety labeling, the
National Child Death Review Case Reporting System found that between 2004 and
2015 across 24 states, an air mattress was the incident sleep place for 108
infants whose deaths were either during sleep or in a sleep environment. At the
same time, design components such as inflatable headboards and memory foam pillow
tops potentially increase the hazard to infants, and marketing changes represent
air mattresses as a preferred low-cost primary sleep environment. Analysis of
current data surveillance systems, published position statements, and consumer
materials from national organizations and federal agencies reveal opportunities
for changing policy to better protect infants from this hazard.
PMID- 28426297
TI - Note From the Editor-in-Chief: Who Wants to Exclude Older LGBT Persons From
Public Health Surveillance?
PMID- 28426296
TI - A Typical Day With Mild Cognitive Impairment.
PMID- 28426295
TI - Review of Recent Methodological Developments in Group-Randomized Trials: Part 1
Design.
AB - In 2004, Murray et al. reviewed methodological developments in the design and
analysis of group-randomized trials (GRTs). We have highlighted the developments
of the past 13 years in design with a companion article to focus on developments
in analysis. As a pair, these articles update the 2004 review. We have discussed
developments in the topics of the earlier review (e.g., clustering, matching, and
individually randomized group-treatment trials) and in new topics, including
constrained randomization and a range of randomized designs that are alternatives
to the standard parallel-arm GRT. These include the stepped-wedge GRT, the
pseudocluster randomized trial, and the network-randomized GRT, which, like the
parallel-arm GRT, require clustering to be accounted for in both their design and
analysis.
PMID- 28426298
TI - Mass Media Campaign to Reduce Consumption of Sugar-Sweetened Beverages in a Rural
Area of the United States.
AB - OBJECTIVES: To evaluate a mass media campaign to reduce the consumption of sugar
sweetened beverages (SSBs). METHODS: We disseminated messages emphasizing the
health risks of SSBs through television, digital channels, and local
organizations over 15 weeks in 2015-2016 in the Tri-Cities region of northeast
Tennessee, southwest Virginia, and southeast Kentucky. We evaluated the campaign
with pre- and post-telephone surveys of adults aged 18 to 45 years in the
intervention area and by examining changes in beverage sales in the intervention
and a matched comparison area in western Virginia. RESULTS: Fifty-four percent of
postcampaign respondents recalled seeing a campaign advertisement. After the
campaign, 53% of respondents believed SSBs were a cause of heart disease, and
respondents were more likely postcampaign to consider SSBs a "big cause of
diabetes" (75% vs 60%; P < .001). Compared with 12 months before, after the start
of the campaign, SSB sales decreased 3.4%, including a 4.1% decrease in soda
sales in the intervention area relative to the comparison area (P < .01).
CONCLUSIONS: This brief media campaign on SSBs was followed by intended changes
in beliefs and consumption. Public Health Implications. Additional media
campaigns on SSBs should be attempted and evaluated.
PMID- 28426299
TI - Effect of Legislation on Indoor Tanning Prevalence in Alabama.
AB - OBJECTIVES: To examine changes in indoor tanning prevalence among Alabama high
school students the year before and after its 2014 legal restrictions compared
with Florida, which had more lenient legislation. METHODS: We analyzed the
Alabama and Florida 2015 Youth Risk Behavior Survey (n = 14 389; population = 1
864 241) by gender, age, year (2013, 2015), state (Alabama, Florida), and year-by
state interactions. RESULTS: Prevalence of indoor tanning was higher among
Alabama youths, but the difference did not significantly change after the law was
passed in Alabama (between-state change differences ranged from a 3.3% increase
among 14-year-old Alabama girls to a 9.7% decrease among 14-year-old Alabama
boys). CONCLUSIONS: We found no significant changes in indoor tanning among
adolescents since the enactment of Alabama's tanning restrictions in 2014. More
oversight and monitoring are needed to ensure that indoor tanning facilities are
compliant with emerging laws.
PMID- 28426300
TI - Overview of Asian American Data Collection, Release, and Analysis: National
Health and Nutrition Examination Survey 2011-2018.
AB - Data System. The National Health and Nutrition Examination Survey (NHANES),
conducted by the National Center for Health Statistics, is a cross-sectional
survey on the health and nutritional status of US adults and children. Data
Collection/Processing. A complex, multistage probability design is used to select
a sample representative of the US civilian, noninstitutionalized population.
NHANES includes in-home interviews, physical examinations, and biospecimen
collection. About 5000 persons are examined annually. Since 2011, NHANES has been
oversampling Asian Americans in addition to traditionally oversampled groups,
including Hispanics and non-Hispanic Blacks. Data Analysis/Dissemination. Data
are publicly released online in 2-year cycles. Some data, because of disclosure
risk, are only available through the Research Data Center. Data users should read
documentation, examine sample sizes and response rates, and account for the
complex survey design. With publicly released data, analyses of Asians as a
single group is only possible; some Asian subgroup analyses may be conducted
through the Research Data Center. Public Health Implications. Oversampling Asians
in NHANES 2011-2018 allows national estimates to be computed on health
conditions, nutrition, and risk factors of public health importance on this
growing subpopulation of Asian Americans.
PMID- 28426301
TI - Small-Group Randomized Controlled Trial to Increase Condom Use and HIV Testing
Among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex With Men.
AB - OBJECTIVES: To evaluate the HOLA en Grupos intervention, a Spanish-language small
group behavioral HIV prevention intervention designed to increase condom use and
HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with
men. METHODS: In 2012 to 2015, we recruited and randomized 304 Hispanic/Latino
men who have sex with men, aged 18 to 55 years in North Carolina, to the 4
session HOLA en Grupos intervention or an attention-equivalent general health
education comparison intervention. Participants completed structured assessments
at baseline and 6-month follow-up. Follow-up retention was 100%. RESULTS: At
follow-up, relative to comparison participants, HOLA en Grupos participants
reported increased consistent condom use during the past 3 months (adjusted odds
ratio [AOR] = 4.1; 95% confidence interval [CI] = 2.2, 7.9; P < .001) and HIV
testing during the past 6 months (AOR = 13.8; 95% CI = 7.6, 25.3; P < .001). HOLA
en Grupos participants also reported increased knowledge of HIV (P < .001) and
sexually transmitted infections (P < .001); condom use skills (P < .001), self
efficacy (P < .001), expectancies (P < .001), and intentions (P < .001); sexual
communication skills (P < .01); and decreased fatalism (P < .001). CONCLUSIONS:
The HOLA en Grupos intervention is efficacious for reducing HIV risk behaviors
among Hispanic/Latino men who have sex with men.
PMID- 28426302
TI - Innovations in Population Health Surveillance: Using Electronic Health Records
for Chronic Disease Surveillance.
AB - With 87% of providers using electronic health records (EHRs) in the United
States, EHRs have the potential to contribute to population health surveillance
efforts. However, little is known about using EHR data outside syndromic
surveillance and quality improvement. We created an EHR-based population health
surveillance system called the New York City (NYC) Macroscope and assessed the
validity of diabetes, hyperlipidemia, hypertension, smoking, obesity, depression,
and influenza vaccination indicators. The NYC Macroscope uses aggregate data from
a network of outpatient practices. We compared 2013 NYC Macroscope prevalence
estimates with those from a population-based, in-person examination survey, the
2013-2014 NYC Health and Nutrition Examination Survey. NYC Macroscope diabetes,
hypertension, smoking, and obesity prevalence indicators performed well, but
depression and influenza vaccination estimates were substantially lower than were
survey estimates. Ongoing validation will be important to monitor changes in
validity over time as EHR networks mature and to assess new indicators. We
discuss NYC's experience and how this project fits into the national context.
Sharing lessons learned can help achieve the full potential of EHRs for
population health surveillance.
PMID- 28426303
TI - Measures of Local Segregation for Monitoring Health Inequities by Local Health
Departments.
AB - OBJECTIVES: To assess the use of local measures of segregation for monitoring
health inequities by local health departments. METHODS: We analyzed preterm birth
and premature mortality (death before the age of 65 years) rates for Boston,
Massachusetts, for 2010 to 2012, using the Index of Concentration at the Extremes
(ICE) and the poverty rate at both the census tract and neighborhood level.
RESULTS: For premature mortality at the census tract level, the rate ratios
comparing the worst-off and best-off terciles were 1.58 (95% confidence interval
[CI] = 1.36, 1.83) for the ICE for income, 1.66 (95% CI = 1.43, 1.93) for the ICE
for race/ethnicity, and 1.63 (95% CI = 1.40, 1.90) for the ICE combining income
and race/ethnicity, as compared with 1.47 (95% CI = 1.27, 1.71) for the poverty
measure. Results for the ICE and poverty measures were more similar for preterm
births than for premature mortality. CONCLUSIONS: The ICE, a measure of social
spatial polarization, may be useful for analyzing health inequities at the local
level. Public Health Implications. Local health departments in US cities can
meaningfully use the ICE to monitor health inequities associated with racialized
economic segregation.
PMID- 28426304
TI - State Preemption: A Significant and Quiet Threat to Public Health in the United
States.
AB - State and local governments traditionally protect the health and safety of their
populations more strenuously than does the federal government. Preemption, when a
higher level of government restricts or withdraws the authority of a lower level
of government to act on a particular issue, was historically used as a point of
negotiation in the legislative process. More recently, however, 3 new preemption
related issues have emerged that have direct implications for public health.
First, multiple industries are working on a 50-state strategy to enact state laws
preempting local regulation. Second, legislators supporting preemptive state
legislation often do not support adopting meaningful state health protections and
enact preemptive legislation to weaken protections or halt progress. Third,
states have begun adopting enhanced punishments for localities and individual
local officials for acting outside the confines of preemption. These actions have
direct implications for health and cover such topics as increased minimum wages,
paid family and sick leave, firearm safety, and nutrition policies. Stakeholders
across public health fields and disciplines should join together in advocacy,
action, research, and education to support and maintain local public health
infrastructures and protections.
PMID- 28426305
TI - US Public Opinion on Carrying Firearms in Public Places.
AB - OBJECTIVES: To estimate US public opinion, overall and by gun ownership status,
about the public places where legal gun owners should be allowed to carry
firearms. METHODS: We fielded an online survey among 3949 adults, including an
oversample of gun owners and veterans, in April 2015. We used cross-tabulations
with survey weights to generate nationally representative estimates. RESULTS:
Fewer than 1 in 3 US adults supported gun carrying in any of the specified
venues. Support for carrying in public was consistently higher among gun owners
than among non-gun owners. Overall, support for carrying in public was lowest for
schools (19%; 95% confidence interval [CI] = 16.7, 21.1), bars (18%; 95% CI =
15.9, 20.6), and sports stadiums (17%; 95% CI = 15.0, 19.5). CONCLUSIONS: Most
Americans, including most gun owners, support restricting public places legal gun
owners can carry firearms. These views contrast sharply with the current trend in
state legislatures of expanding where, how, and by whom guns can be carried in
public. Recent state laws and proposed federal legislation that would force
states to honor out-of-state concealed carry permits are out of step with
American public opinion.
PMID- 28426306
TI - Machine Learning for Social Services: A Study of Prenatal Case Management in
Illinois.
AB - OBJECTIVES: To evaluate the positive predictive value of machine learning
algorithms for early assessment of adverse birth risk among pregnant women as a
means of improving the allocation of social services. METHODS: We used
administrative data for 6457 women collected by the Illinois Department of Human
Services from July 2014 to May 2015 to develop a machine learning model for
adverse birth prediction and improve upon the existing paper-based risk
assessment. We compared different models and determined the strongest predictors
of adverse birth outcomes using positive predictive value as the metric for
selection. RESULTS: Machine learning algorithms performed similarly,
outperforming the current paper-based risk assessment by up to 36%; a refined
paper-based assessment outperformed the current assessment by up to 22%. We
estimate that these improvements will allow 100 to 170 additional high-risk
pregnant women screened for program eligibility each year to receive services
that would have otherwise been unobtainable. CONCLUSIONS: Our analysis exhibits
the potential for machine learning to move government agencies toward a more data
informed approach to evaluating risk and providing social services. Overall, such
efforts will improve the efficiency of allocating resource-intensive
interventions.
PMID- 28426307
TI - How California Prepared for Implementation of Physician-Assisted Death: A Primer.
AB - Physician-assisted death is now legal in California, and similar laws are being
considered in many other states. The California law includes safeguards, yet
health care providers will face practical and ethical issues while implementing
physician-assisted death that are not addressed by the law. To help providers and
health care facilities in California prepare to provide optimal care to patients
who inquire about physician-assisted death, we brought together experts from
California, Oregon, and Washington. We convened a conference of 112 stakeholders
in December 2015, and herein present their recommendations. Themes of
recommendations regarding implementation include (1) institutions should develop
and revise physician-assisted death policies; (2) legal physician-assisted death
will have implications for California's culturally and socioeconomically diverse
population, and for patients from vulnerable groups; (3) conscientious objection
and moral distress for health care providers must be considered; and (4)
palliative care is essential to the response to the law. The expert conference
participants' insights are a valuable guide, both for providers and health care
facilities in California planning or revising their response, and for other
jurisdictions where physician-assisted death laws are being considered or
implemented.
PMID- 28426308
TI - Humanitarian Needs Among Displaced and Female-Headed Households in Government
Controlled Areas of Syria.
AB - OBJECTIVES: To identify unmet needs and assistance priorities of displaced and
female-headed households in government-controlled areas of Syria. METHODS: In mid
2016, we undertook a survey of accessible areas, largely urban and government
controlled, to identify unmet needs and assistance priorities. We used a cluster
design with probability sampling to attain a final sample of 2405 households from
10 of 14 governorates; 31 of 65 (47.7%) districts were included that are home to
38.1% of people in need. RESULTS: Displaced and female-headed households were
more vulnerable than nondisplaced and male-headed households in numerous sectors.
Despite approximately half of surveyed households reporting receipt of
humanitarian assistance in the preceding month and apparently effective targeting
of assistance by vulnerability, unmet needs were nearly ubiquitous. CONCLUSIONS:
The humanitarian situation in inaccessible areas of Syria is likely to be
considerably worse; thus, findings presented here likely underestimate
humanitarian needs. Efforts to expand support to Syria's most vulnerable
households are desperately needed as are innovative targeting and modalities that
enable more efficient and effective assistance.
PMID- 28426309
TI - LGBTQ Health Surveillance: Data = Power.
PMID- 28426310
TI - A Public Health Approach to Hepatitis C in an Urban Setting.
AB - The clinical consequences of HCV infection are increasing because the population
with the highest prevalence of the infection, persons born between 1945 and 1965,
is aging. As a result, health care expenditures are expected to increase. Now
that a cure for HCV infection is the norm, a public health approach is necessary
to identify, link to care, and treat infected persons and prevent new infections.
We believe that the success of public health interventions, such as those for
tuberculosis, can be translated to HCV infection. New York City has many HCV
infected residents and has developed a public health approach to controlling the
HCV epidemic. It encompasses surveillance and monitoring, case finding, linkage
to care, care coordination, increasing clinical provider capacity for screening
and treatment, increasing public awareness, and primary prevention.
PMID- 28426311
TI - The Zika Virus Outbreak in Brazil: Knowledge Gaps and Challenges for Risk
Reduction.
AB - We analyzed uncertainties and complexities of the Zika virus outbreak in Brazil,
and we discuss risk reduction for future emergencies. We present the public
health situation in Brazil and concurrent determinants of the epidemic and the
knowledge gaps that persist despite building evidence from research, making
public health decisions difficult. Brazil has adopted active measures, but
producing desired outcomes may be uncertain because of partial or unavailable
information. Reducing population group vulnerabilities and acting on
environmental issues are medium- to long-term measures. Simultaneously dealing
with information gaps, uncontrolled disease spread, and vulnerabilities is a new
risk scenario and must be approached decisively to face emerging biothreats.
PMID- 28426312
TI - Safe Sex in the 1970s: Community Practitioners on the Eve of AIDS.
AB - In the 1970s, groups of gay and gay-allied health professionals began to
formulate guidelines for safer sexual activity, several years before HIV/AIDS.
Through such organizations as the National Coalition of Gay Sexually Transmitted
Disease Services, Bay Area Physicians for Human Rights, and the Sisters of
Perpetual Indulgence, these practitioners developed materials that would define
sexual health education for the next four decades, as well as such concepts as
"bodily fluids" and the "safe sex hanky." To do so, they used their dual
membership in the community and the health professions. Although the dichotomy
between the gay community and the medical establishment helped define the early
history of HIV/AIDS, the creative work of these socially "amphibious" activists
played an equally important part. Amid current debates over preexposure
prophylaxis against HIV and Zika virus transmission, lessons for sexual health
include the importance of messaging, the difficulty of behavioral change, and the
vitality of community-driven strategies to mitigate risk.
PMID- 28426313
TI - Restrictions of Hepatitis C Treatment for Substance-Using Medicaid Patients: Cost
Versus Ethics.
AB - Medicaid programs provide health insurance coverage for many patients with
hepatitis C, a public health problem for which effective but very expensive
treatments are now available. Facing constrained budgets, most states adopted
prior authorization criteria for sofosbuvir, the first of these agents. Using fee
for-service utilization data from 42 Medicaid programs in 2014, we found that
strict behavioral criteria-those that limited coverage on the basis of drug or
alcohol use and included specific abstinence or treatment requirements-were
associated with significantly less spending on sofosbuvir. Despite the potential
cost savings, such criteria raise troubling questions in terms of public health
as well as medical ethics, clinical evidence, and potentially federal law.
Decision-makers should reject these requirements in Medicaid coverage policy and
pursue national and state policy strategies to balance short-term budgetary
realities with long-term public health benefits.
PMID- 28426314
TI - The Influence of College Attendance on Risk for Marijuana Initiation in the
United States: 1977 to 2015.
AB - OBJECTIVES: To examine a potential increase in marijuana initiation among US
college students as compared with their age peers not in college before and after
2013, a watershed year for increasing tolerance of marijuana use in the United
States. METHODS: Data come from the Monitoring the Future study, which has
followed longitudinal panels drawn from annual nationally representative,
baseline samples of 12th-grade students starting with the class of 1976. We
studied panel members aged 19 to 22 years who had never used marijuana by 12th
grade between 1977 and 2015. RESULTS: College as a risk factor for marijuana
initiation has increased significantly since 2013. The increased probability of
past-year marijuana use for those enrolled versus not enrolled in college was 51%
in 2015, 41% in 2014, and 31% in 2013; it averaged 17% to 22% from 1977 to 2012
among youths who had never used marijuana by 12th grade. CONCLUSIONS: College has
grown as a risk factor for marijuana initiation since 2013. Public Health
Implications. College students are in position to usher in new increases in
population marijuana use unless colleges soon address the issue with new or
modified programs for marijuana prevention and intervention.
PMID- 28426315
TI - Medicaid Expansion and ACA Repeal: Evidence From Ohio.
AB - OBJECTIVES: To examine the health insurance coverage options for Medicaid
expansion enrollees if the Affordable Care Act (ACA) is repealed, using evidence
from Ohio, where more than half a million adults have enrolled in the state's
Medicaid program through the ACA expansion. METHODS: The Ohio Medicaid Assessment
Survey interviewed 42 000 households in 2015. We report data from a unique
battery of questions designed to identify insurance coverage immediately prior to
Medicaid enrollment. RESULTS: Ninety-five percent of new Medicaid enrollees in
Ohio did not have a private health insurance option immediately before
enrollment. These new enrollees are predominantly older, low-income Whites with a
high school education or less. Only 5% of new Medicaid enrollees were eligible
for an employer-sponsored insurance plan to which they could potentially return
in the case of repeal of the ACA. CONCLUSIONS: The vast majority of Medicaid
expansion enrollees would have no plausible pathway to obtaining private-sector
insurance if the ACA were repealed. Demographic similarities between the
expansion population and 2016 exit polls suggest that coverage losses would fall
disproportionately on members of the winning Republican coalition.
PMID- 28426316
TI - Framing Mechanisms Linking HIV-Related Stigma, Adherence to Treatment, and Health
Outcomes.
AB - We present a conceptual framework that highlights how unique dimensions of
individual-level HIV-related stigma (perceived community stigma, experienced
stigma, internalized stigma, and anticipated stigma) might differently affect the
health of those living with HIV. HIV-related stigma is recognized as a barrier to
both HIV prevention and engagement in HIV care, but little is known about the
mechanisms through which stigma leads to worse health behaviors or outcomes. Our
conceptual framework posits that, in the context of intersectional and structural
stigmas, individual-level dimensions of HIV-related stigma operate through
interpersonal factors, mental health, psychological resources, and biological
stress pathways. A conceptual framework that encompasses recent advances in
stigma science can inform future research and interventions aiming to address
stigma as a driver of HIV-related health.
PMID- 28426317
TI - Trends in Fighting and Violence Among Adolescents in the United States, 2002
2014.
AB - OBJECTIVES: To examine trends in and correlates of fighting and violence among
youths from the 3 largest racial/ethnic groups in the United States. METHODS: We
derived race/ethnicity-specific prevalence estimates for fighting, group
fighting, and attacks with intent to harm from the National Survey on Drug Use
and Health, a population-based study of youths aged 12 to 17 years. RESULTS: The
prevalence of youth fighting and violence decreased significantly in all
racial/ethnic groups over the study period (2002-2014), dropping from a high of
33.6% in 2003 to a low of 23.7% in 2014, reflecting a 29% decrease in the
relative proportion of young people involved in these behaviors. However, there
was also a clear severity gradient in which year-by-year point estimates for
fighting and violence were consistently highest among non-Hispanic African
American youths, followed by Hispanic and then non-Hispanic White youths.
CONCLUSIONS: Although fighting and violence are on the decline among young people
in general and across racial/ethnic subgroups, there is a stable pattern of
disparities in youth involvement in these behaviors.
PMID- 28426318
TI - US State Statutes Banning Powdered Alcohol: Exceptions and Penalties.
AB - To examine state statutes banning powdered alcohol, we identified relevant
statutes in all 50 states and the District of Columbia through a search (initial
search March 2016; follow-up search November 2016) using the legal research
database LexisNexis. To identify the laws, we used the following search terms:
"concentrated alcohol," "crystalline alcohol," "granulated alcohol," "palcohol,"
and "powdered alcohol." As of November 2016, 31 states had statutory bans on
powdered alcohol. Statutes in 22 states outline penalties for violating the
state's ban on powdered alcohol. Five states include suspension and revocation of
alcohol beverage licenses and permits among the penalties. Thirteen states
provide exceptions to their ban on powdered alcohol for bona fide scientific
research. Twelve states have exceptions for powdered alcohol designed for
commercial use or not intended for human consumption. With concerns expressed
that powdered alcohol may lead to greater alcohol consumption, particularly among
minors, the majority of state legislatures have demonstrated their willingness to
restrict access to novel alcohol products to protect the public's health.
However, the effectiveness of these laws should be evaluated if the product does
become available.
PMID- 28426319
TI - The Monetary Cost of Sexual Assault to Privately Insured US Women in 2013.
AB - OBJECTIVES: To determine whether privately insured female rape victims were
billed for charges associated with a specific rape in the United States. METHODS:
We examined 2013 de-identified patient data from Truven Analytics Health
MarketScan database for an assault that occurred by using International
Classification of Diseases, Ninth Revision, code E960.1. RESULTS: Analysis of
insurance providers' payment patterns for 1355 incident events to female victims
aged between 16 and 61 years revealed that victims remit, on average, 14% or $948
of the rape cost, whereas insurance providers pay 86% or $5789 of the total cost.
CONCLUSIONS: Hospital billing procedures for privately insured victims of rape
across the United States are not separate from billing procedures for privately
insured nonrape patients. This standardized procedure leads hospitals to bill
victims directly for services not paid under the victims' insurance policy.
Public Health Implications. The Violence Against Women Act (passed in 1994,
reauthorized in 2000, 2005, and 2013) must be amended to mandate that all costs
incurred because of rape are not passed on to the victim.
PMID- 28426321
TI - Hansae Vietnam's garment factory: Latest example of how corporate social
responsibility has failed to protect workers.
PMID- 28426320
TI - Transient exposure to androgens induces a remarkable self-sustained quiescent
state in dispersed prostate cancer cells.
AB - Cellular quiescence is a reversible cell growth arrest that is often assumed to
require a persistence of non-permissive external growth conditions for its
maintenance. In this work, we showed that androgen could induce a quiescent state
that is self-sustained in a cell-autonomous manner through a "hit and run"
mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon
required the set-up of a sustained redox imbalance and TGFbeta/BMP signaling that
were dependent on culturing cells at low density. At medium cell density,
androgens failed to induce such a self-sustained quiescent state, which
correlated with a lesser induction of cell redox imbalance and oxidative stress
markers like CDKN1A. These effects of androgens could be mimicked by transient
overexpression of CDKN1A that triggered its own expression and a sustained SMAD
phosphorylation in cells cultured at low cell density. Overall, our data suggest
that self-sustained but fully reversible quiescent states might constitute a
general response of dispersed cancer cells to stress conditions.
PMID- 28426322
TI - Formative Research to Design a Promotional Campaign to Increase Drinking Water
among Central American Latino Youth in an Urban Area.
AB - Latinos consume more sugary drinks and less water than other demographic groups.
Our objective was to understand beverage choice motivations and test promotional
concepts that can encourage Central American Latino urban youth to drink more
water. Two rounds of focus group discussions were conducted (n = 10 focus groups,
61 participants, 6-18 years old). Data were transcribed verbatim and analyzed
using inductive and deductive coding approaches. Youth motivations for drinking
water were shaped by level of thirst, weather, energy, and perceptions of health
benefits. Youth were discouraged from drinking water due to its taste and
perceptions of the safety and cleanliness of tap water. Youth beverage preference
depended on what their friends were drinking. Availability of water versus other
beverages at home and other settings influenced their choice. Promotional
materials that included mixed language, informative messages about the benefits
of drinking water, and celebrities or athletes who were active, energized, and
drinking water were preferred. A promotional campaign to increase water
consumption among these Latino youth should include bicultural messages to
underscore the power of water to quench true thirst, highlight the health
benefits of drinking water, and address the safety of tap water.
PMID- 28426323
TI - Letters From Our Readers.
PMID- 28426324
TI - Letters From Our Readers.
PMID- 28426325
TI - Letters From Our Readers.
PMID- 28426328
TI - Fast Food or Slow Food Orthodontics? Part 2.
PMID- 28426327
TI - Letters From Our Readers.
PMID- 28426329
TI - Mathematical modelling of CRISPR-Cas system effects on biofilm formation.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR), linked with
CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against
bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity
increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas
genes have been implicated in reducing biofilm formation in lysogenized cells.
Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions,
particularly in a biofilm. In this contribution, we develop and analyse a series
of dynamical systems to elucidate and disentangle these interactions. Two
competition models are used to study the effects of lysogens (first model) and
CRISPR-immune bacteria (second model) in the biofilm. In the third model, the
effect of delivering lysogens to a CRISPR-immune biofilm is investigated. Using
standard analyses of equilibria, stability and bifurcations, our models predict
that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and
thus suggest strategies to eliminate phage-resistant biofilms.
PMID- 28426330
TI - The transformation of the meaning of death in complicated grief group therapy for
survivors of suicide: A treatment process analysis using the meaning of loss
codebook.
AB - We examined the therapeutic process of grief change in survivors of suicide
participating in complicated grief group therapy (CGGT) using the meaning of loss
codebook (MLC). Complicated grief group therapy is a multimodal group
psychotherapy designed to restore normal grieving in persons with complicated
grief. Using video data, we evaluated transition points in psychotherapy
associated with meaning reconstruction: retelling the narrative of the death,
having an imaginal conversation with the deceased, and memory integration. The
MLC codes captured most of the voiced statements of participants, provided a
valuable lens for articulating the therapeutic process, and affirmed that CGGT
facilitated effective grief.
PMID- 28426331
TI - Effect of deletion of 2,3-butanediol dehydrogenase gene (bdhA) on acetoin
production of Bacillus subtilis.
AB - The present work aims to block 2,3-butanediol synthesis in acetoin fermentation
of Bacillus subtilis. First, we constructed a recombinant strain BS168D by
deleting the 2,3-butanediol dehydrogenase gene bdhA of the B. subtilis168, and
there was almost no 2,3-butanediol production in 20 g/L of glucose media. The
acetoin yield of BS168D reached 6.61 g/L, which was about 1.5 times higher than
that of the control B. subtilis168 (4.47 g/L). Then, when the glucose
concentration was increased to 100 g/L, the acetoin yield reached 24.6 g/L, but
2.4 g/L of 2,3-butanediol was detected at the end of fermentation. The analysis
of 2,3-butanediol chiral structure indicated that the main 2,3-butanediol
production of BS168D was meso-2,3-butanediol, and the bdhA gene was only
responsible for (2R,3R)-2,3-butanediol synthesis. Therefore, we speculated that
there may exit another pathway relating to the meso-2,3-butanediol synthesis in
the B. subtilis. In addition, the results of low oxygen condition fermentation
showed that deletion of bdhA gene successfully blocked the reversible
transformation between acetoin and 2,3-butanediol and eliminated the effect of
dissolved oxygen on the transformation.
PMID- 28426333
TI - Existence and uniqueness for a coupled PDE model for motor-induced microtubule
organization.
AB - Microtubules (MTs) are protein filaments that provide structure to the
cytoskeleton of cells and a platform for the movement of intracellular
substances. The spatial organization of MTs is crucial for a cell's form and
function. MTs interact with a class of proteins called motor proteins that can
transport and position individual filaments, thus contributing to overall
organization. In this paper, we study the mathematical properties of a coupled
partial differential equation (PDE) model, introduced by White et al. in 2015,
that describes the motor-induced organization of MTs. The model consists of a
nonlinear coupling of a hyperbolic PDE for bound motor proteins, a parabolic PDE
for unbound motor proteins, and a transport equation for MT dynamics. We locally
smooth the motor drift velocity in the equation for bound motor proteins. The
mollification is not only critical for the analysis of the model, but also adds
biological realism. We then use a Banach Fixed Point argument to show local
existence and uniqueness of mild solutions. We highlight the applicability of the
model by showing numerical simulations that are consistent with in vitro
experiments.
PMID- 28426332
TI - Buprenorphine Treatment and Patient Use of Health Services after the Affordable
Care Act in an Integrated Health Care System.
AB - The Affordable Care Act (ACA) was expected to benefit patients with substance use
disorders, including opioid use disorders (OUDs). This study examined
buprenorphine use and health services utilization by patients with OUDs pre- and
post-ACA in a large health care system. Using electronic health record data, we
examined demographic and clinical characteristics (substance use, psychiatric and
medical conditions) of two patient cohorts using buprenorphine: those newly
enrolled in 2012 ("pre-ACA," N = 204) and in 2014 ("post-ACA," N = 258). Logistic
and negative binomial regressions were used to model persistent buprenorphine
use, and to examine whether persistent use was related to health services
utilization. Buprenorphine patients were largely similar pre- and post-ACA,
although more post-ACA patients had a marijuana use disorder (p < .01). Post-ACA
patients were more likely to have high-deductible benefit plans (p < .01). Use of
psychiatry services was lower post-ACA (IRR: 0.56, p < .01), and high-deductible
plans were also related to lower use of psychiatry services (IRR: 0.30, p < .01).
The relationship between marijuana use disorder and prescription opioid use is
complex, and deserves further study, particularly with increasingly widespread
marijuana legalization. Access to psychiatry services may be more challenging for
buprenorphine patients post-ACA, especially for patients with deductible plans.
PMID- 28426334
TI - Myopigenic Activity Change and Its Risk Factors in Urban Students in Beijing:
Three-Year Report of Beijing Myopia Progression Study.
AB - PURPOSE: To investigate the myopigenic activity change and its risk factors in
urban students in Beijing. METHODS: A total of 241 primary or secondary students
aged 6-17 years from the Beijing Myopia Progression Study (BMPS) were re-examined
3 years after their baseline enrollment. A detailed questionnaire was
administered to assess myopigenic activities at both baseline and at the 3-year
follow-up. Altogether, 217 students (90.0%) with completed data were included in
the analysis. RESULTS: Compared to baseline, primary students (n = 123) had
significant increases in outdoor sports time (mean +/- standard deviation: 3.5 +/
4.3 vs. 2.4 +/- 3.0 hours/week, p = 0.02), near work time (32.1 +/- 13.4 vs.
24.8 +/- 9.2 hours/week, p < 0.001), diopter hours (128.8 +/- 53.3 vs. 97.5 +/-
35.9 diopter hours/week, p < 0.001), and indoor time (53.8 +/- 22.8 vs. 41.4 +/-
16.9 hours/week, p < 0.001) at the 3-year follow-up. At both baseline and follow
up, females spent less time than males on outdoor sports (baseline: 2.4 +/- 2.8
vs. 4.0 +/- 5.2 hours/week, p = 0.006; follow-up: 2.3 +/- 3.1 vs. 5.1 +/- 5.0
hours/week, p < 0.001), and total outdoors (baseline: 11.9 +/- 7.9 vs. 14.4 +/-
9.5 hours/week, p = 0.03; follow-up: 10.5 +/- 8.2 vs. 13.9 +/- 9.6 hours/week, p
= 0.005). In the multivariate regression analysis after adjustment by student's
gender, younger students had more increase in both near work time (slope = -0.99
hours/week for age, p = 0.009) and indoor time (slope = -2.04 hours/week for age,
p = 0.001). CONCLUSIONS: During the 3-year follow-up, primary students had more
myopigenic activities. Female students had more myopigenic activities than males
at both baseline and follow-up. Children's age was a significant risk factor for
this myopigenic activity change.
PMID- 28426335
TI - Chaplaincy Encounters Following a Suicide Attempt.
AB - This descriptive study examines the provision of chaplaincy services to veterans
who sought health care at a Department of Veterans Affairs (VA) Medical Center
following a suicide attempt. A system-wide VA database of suicidal behavior was
used to identify a cohort of n = 22,701 veterans who survived a suicide attempt.
Next, an electronic review of VA clinical records found that n = 7,447 (32.8%)
received chaplaincy services in the 30 days following their attempt. Of this
group, the overwhelming majority of first chaplaincy encounters took place in in
patient settings: n = 6890 (92.5%). First chaplaincy encounters most often
occurred 1-7 days following the attempt: n = 5,033 (67.6%). Most chaplaincy
service users had only one chaplaincy encounter: n = 3,514 (47.2%). The findings
suggest that, at VA Medical Centers, a relatively sizeable percentage of suicide
attempt survivors have contact with chaplaincy services. Additional research is
needed to ascertain if chaplaincy services yield any therapeutic benefit for this
group.
PMID- 28426336
TI - Effect of Laser Energy and Tip Insertion Depth on the Pressure Generated Outside
the Apical Foramen During Er:YAG Laser-Activated Root Canal Irrigation.
AB - OBJECTIVE: The risk of extrusion of irritative irrigants into the extraradicular
tissue should be minimized during root canal irrigation. This study aimed to
examine the pressure generated outside the apex during Er:YAG laser-activated
irrigation (LAI) in comparison with passive ultrasonic irrigation (PUI) and
conventional syringe irrigation (SI). BACKGROUND DATA: LAI is reported to be
efficient for root canal debridement, whereas the apical pressure generated
during LAI has not been investigated in detail. METHODS: Plastic root canal
models (apical diameter = 0.40 mm, taper = 6%, and length = 20 mm) were irrigated
with water using either LAI with an Er:YAG laser (Erwin AdvEr; 30, 50, or 70 mJ,
10 pps), PUI, or SI. The tip insertion depth was set at 2, 5, or 10 mm from the
apex. The pressure generated outside the apical foramen was measured with a
pressure sensor connected to the apex of the model. RESULTS: When the tip was
positioned at 2 mm and the power setting was changed, the mean maximum pressure
values were LAI (30 mJ) = PUI < LAI (70 mJ) < SI (p < 0.05). When LAI was
performed at 70 mJ and the tip was positioned at 5 or 10 mm, the pressure values
were PUI < LAI = SI (p < 0.05). CONCLUSIONS: LAI generated similar or lower
pressure outside the apical foramen compared with SI, irrespective of the laser
energy and tip insertion depth examined. However, LAI generated higher pressure
compared with PUI.
PMID- 28426337
TI - The Goal of Better Understanding the Applications of Laser Therapy in Periodontal
Disease Management in the 21st Century.
PMID- 28426338
TI - Causes of death in long-term lung cancer survivors: a SEER database analysis.
AB - BACKGROUND: Long-term (>5 years) lung cancer survivors represent a small but
distinct subgroup of lung cancer patients and information about the causes of
death of this subgroup is scarce. METHODS: The Surveillance, Epidemiology and End
Results (SEER) database (1988-2008) was utilized to determine the causes of death
of long-term survivors of lung cancer. Survival analysis was conducted using
Kaplan-Meier analysis and multivariate analysis was conducted using a Cox
proportional hazard model. Clinicopathological characteristics and survival
outcomes were assessed for the whole cohort. RESULTS: A total of 78,701 lung
cancer patients with >5 years survival were identified. This cohort included
54,488 patients surviving 5-10 years and 24,213 patients surviving >10 years.
Among patients surviving 5-10 years, 21.8% were dead because of primary lung
cancer, 10.2% were dead because of other cancers, 6.8% were dead because of
cardiac disease and 5.3% were dead because of non-malignant pulmonary disease.
Among patients surviving >10 years, 12% were dead because of primary lung cancer,
6% were dead because of other cancers, 6.9% were dead because of cardiac disease
and 5.6% were dead because of non-malignant pulmonary disease. On multivariate
analysis, factors associated with longer cardiac-disease-specific survival in
multivariate analysis include younger age at diagnosis (p < .0001), white race
(vs. African American race) (p = .005), female gender (p < .0001), right-sided
disease (p = .003), adenocarcinoma (vs. large cell or small cell carcinoma),
histology and receiving local treatment by surgery rather than radiotherapy (p <
.0001). CONCLUSION: The probability of death from primary lung cancer is still
significant among other causes of death even 20 years after diagnosis of lung
cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a
considerable proportion of deaths in long-term lung cancer survivors.
PMID- 28426339
TI - Fasting levels of insulin and amylin after acute pancreatitis are associated with
pro-inflammatory cytokines.
AB - BACKGROUND: The prevalence of metabolic diseases continues to rise worldwide,
with a growing recognition of metabolic dysregulation after acute inflammatory
diseases such as acute pancreatitis (AP). Adipokines and cytokines play an
important role in metabolism and the course of AP, but there is a paucity of
research investigating their relationship with pancreatic hormones after AP. This
study aimed to explore associations between pancreatic hormones and adipokines as
well as cytokines to provide insights into the pathophysiology of altered
pancreatic hormone secretion following AP [corrected]. METHODS: A total of 83
patients previously diagnosed with AP and no prior diabetes or pre-diabetes were
recruited into this cross-sectional follow up study. Fasting venous blood samples
were collected to analyse a panel of pancreatic hormones and derivatives (amylin,
C-peptide, glucagon, insulin, pancreatic polypeptide, somatostatin), adipokines
(adiponectin, leptin, retinol binding protein-4, and resistin), and cytokines
(interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumour
necrosis factor-alpha (TNF-alpha)). Linear regression analyses were used, and
potential confounders were adjusted for in multivariate analyses. RESULTS:
Insulin was significantly associated with IL-6 in both unadjusted and adjusted
models (p = .029 and p = .040, respectively). Amylin was significantly associated
with MCP-1 in the unadjusted model (p = .046), and TNF-alpha in unadjusted and
adjusted models (p = .025 and p = .027, respectively). CONCLUSIONS: Insulin and
amylin have a strong positive association with pro-inflammatory cytokines in
patients following an episode of AP. These associations have possible relevance
in the development of diabetes associated with diseases of the exocrine pancreas,
providing the opportunity to develop novel treatment paradigms.
PMID- 28426340
TI - A Novel Recombinant Canine Adenovirus Type 1 Detected from Acute Lethal Cases of
Infectious Canine Hepatitis.
AB - In this study, canine adenoviruses (CAdVs) from two acute fatal cases of
infectious canine hepatitis (ICH) were analyzed using molecular detection and
sequencing of the pVIII, E3, and fiber protein genes. Pathological findings in
affected dogs were typical for CAdV-1 associated disease, characterized by severe
centrilobular to panlobular necrohemorrhagic hepatitis and the development of
disseminated intravascular coagulation in the terminal stages of disease.
Comparison of partial genome sequences revealed that although these newly
detected viruses mainly had CAdV-1 genome characteristics, their pVIII gene was
more similar to that of CAdV-2. This likely suggests that a recombination has
occurred between CAdV-1 and CAdV-2, which possibly explains the cause of vaccine
failure or increased virulence of the virus in the observed ICH cases.
PMID- 28426341
TI - Mydriatics release from solid and semi-solid ophthalmic formulations using
different in vitro methods.
AB - The aim of the present paper was the development of semi-solid (hydrogels) and
solid (film) ophthalmic formulations for the controlled release of two
mydriatics: phenylephrine and tropicamide. The formulations - based on
polyvinylalcohol and hyaluronic acid - were characterized, and release studies
were performed with three different in vitro set-ups, i.e. Franz-type diffusion
cell, vial method and inclined plane; for comparison, a solution and a commercial
insert, both clinically used to induce mydriasis, were evaluated. Both gels and
film allowed for a controlled release of drugs, appearing a useful alternative
for mydriatics administration. However, the release kinetic was significantly
influenced by the method used, highlighting the need for optimization and
standardization of in vitro models for the evaluation of drug release from
ophthalmic dosage forms.
PMID- 28426342
TI - Perceived ideal body size of Ghanaian women: "Not too skinny, but not too fat".
AB - Body size issues are gaining public health attention because of the fast rising
epidemic of overweight and obesity across the globe. This study explored Ghanaian
women's subjective perceptions regarding ideal body size for women. A purposive
sampling strategy was employed in recruiting 36 women across the body weight
spectrum from Tamale (n = 17) and Accra (n = 19) in Ghana. Qualitative data were
obtained from in-depth interviews using a semi-structured interview guide. Data
from the interviews were analyzed deductively. The mean body mass index of
participants was 33.5 +/- 10 kg/m2: sixteen of the participants were obese, eight
were overweight, eleven were normal weight, and one was underweight. The
participants almost unanimously had a preference for an ideal body size slightly
above the normal, but not necessarily obese. Typically described as "not too
skinny, but not too fat," this preferred ideal reflected a fuller, curvier, and
shapelier body, as opposed to the Western ideal of thinner body type. Women often
felt pressured by peers and family members to have a slightly heavier body size.
Health education efforts are needed to focus on messages that seek to challenge
existing body size perceptions that may inhibit women's willingness to maintain a
healthy body weight.
PMID- 28426343
TI - De Novo Mutation of KAT6B Gene Causing Atypical Say-Barber-Biesecker-Young
Simpson Syndrome or Genitopatellar Syndrome.
AB - Mutations in KAT6B gene are responsible for Say-Barber-Biesecker-Young-Simpson
syndrome (SBBYSS) and genitopatellar syndrome (GPS), with most mutations
occurring in exon 18. A 4-year-old Chinese boy presented with short stature but
no other clinical features of SBBYSS or GPS had a de novo novel nonsense
pathogenic mutation in exon 14 of the KAT6B gene at position c.2636T>A
(p.Leu879X). The correlation analysis of genotype-phenotype indicated distinctive
clinical features (short stature, growth hormone deficiency, and delayed bone
age) compared with the classical mutations of KAT6B gene. To the best of our
knowledge, this is the first report of KAT6B gene mutation in any Chinese
individual. This work expands the mutant phenotypic spectrum of the KAT6B gene.
PMID- 28426344
TI - Primary Pediatric Breast Lesions: Comparing the Prevalence of Malignancies in the
Middle East with North America; Review of 1031 Cases.
AB - Benign breast masses are uncommon but are becoming more recognized among the
pediatric population. Malignant breast lesions are very rare. The aim of our
study was to review and compare the demographics, clinical presentation,
treatment, and outcomes of breast lesions, including primary malignancies, and to
discuss theories that may explain why there is an increased rate of breast
cancers diagnosed at a younger age in the Egyptian population. A total of 1031
cases were reviewed. Comparisons were made between the Egyptian (n = 846) and US
(n = 185) cohorts. There were 30 (3.5%) malignant tumors in the Egyptian group
with 17 (2%) deaths versus 3 (1.6%) malignant tumors in the US group with 2 (1%)
deaths (p = 0.247). The relative risk of breast cancer in the Egyptian group was
2.16 (95% confidence interval (CI): 0.67-7.01) compared with the US group. The
trend for increased risk of breast cancer in Egypt may be due to delayed
diagnosis because of decreased awareness.
PMID- 28426345
TI - Economic evaluation of ezetimibe treatment in combination with statin therapy in
the United States.
AB - AIMS: This study assessed the cost-effectiveness of ezetimibe with statin therapy
vs statin monotherapy from a US payer perspective, assuming the impending patent
expiration of ezetimibe. METHODS: A Markov-like economic model consisting of 28
distinct health states was used. Model population data were obtained from US
linked claims and electronic medical records, with inclusion criteria based on
diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses,
and cost-effectiveness analyses. The base-case scenario was used to evaluate the
cost-effectiveness of adding ezetimibe 10 mg to statin in patients aged 35-74
years with a history of coronary heart disease (CHD) and/or stroke, and with low
density lipoprotein cholesterol (LDL-C) levels >=70 mg/dL over a lifetime
horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into
account the impending patent expiration in the second quarter of 2017. Sub-group
analyses included patients with LDL-C levels >=100 mg/dL and patients with
diabetes with LDL-C levels >=70 mg/dL. RESULTS: The lifetime discounted
incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was
$9,149 per quality-adjusted life year (QALY) for the base-case scenario. For
patients with LDL-C levels >=100 mg/dL, the ICER was $839/QALY; for those with
diabetes and LDL-C levels >=70 mg/dL, it was $560/QALY. One-way sensitivity
analyses showed that the model was sensitive to changes in cost of ezetimibe,
rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base
case and sub-group analyses. LIMITATIONS: Indirect costs or treatment
discontinuation estimation were not included. CONCLUSIONS: Compared with statin
monotherapy, ezetimibe with statin therapy was cost-effective for secondary
prevention of CHD and stroke and for primary prevention of these conditions in
patients whose LDL-C levels are >=100 mg/dL and in patients with diabetes, taking
into account a 90% cost reduction for ezetimibe.
PMID- 28426346
TI - Correlates of Current Smoking Among Adults Served by the Public Mental Health
System.
AB - OBJECTIVE: As part of a study of health status among 457 adults with
diagnostically heterogeneous serious mental illnesses served by the public mental
health system in four U.S. states, we assessed predictors of current cigarette
smoking. METHODS: We examined bivariate relationships between smoking status and
risks for drug and alcohol use disorders, residential setting, parental status,
and employment. Finally, we used multivariable logistic regression to predict
current smoking, controlling for significant confounds. RESULTS: Of the total
sample, 44% of participants reported that they currently smoked and most (62%)
were moderately to severely nicotine-dependent. Those at high risk for drug use
disorders were more than three times as likely and those at high risk for alcohol
use disorders were more than twice as likely to smoke, compared to their
counterparts with little or no drug or alcohol use disorder risk. Controlling for
all other model variables including drug and alcohol disorder risk, current
smokers were less likely to be parents and more likely to reside in supervised
settings than nonsmokers. Younger people and those without a college degree were
more likely to smoke, controlling for all other model variables. CONCLUSIONS:
Given the high degree of comorbidity of smoking, alcohol disorders, and drug use
disorders, the authors highlight the need for integrated interventions that
address these issues simultaneously.
PMID- 28426347
TI - Mismatch repair regulates Cdt1 after UV damage.
PMID- 28426348
TI - Traumatic brain injury and lifetime suicidality: Applying the interpersonal
psychological theory perspective.
AB - The present article investigates the traumatic brain injury (TBI)-suicide link,
assessing whether (a) TBI accounts for variance in suicide risk, and (b) the
interpersonal-psychological theory of suicide can be applied to TBI status.
Matched case-control procedures applied to archival college student health data
identified TBI and non-TBI subsamples (84 total). Individuals with a TBI
possessed higher suicide risk than those without. Even accounting for the
relative influence of strong suicide risk factors (i.e., depression, perceived
burdensomeness, thwarted belongingness, and acquired capability), TBI was
robustly associated with suicide risk. TBI history would be valuable to ascertain
in assessing suicide risk.
PMID- 28426349
TI - RNA-binding protein RBM14 regulates dissociation and association of non
homologous end joining proteins.
AB - Defects in the DNA damage response (DDR) are associated with multiple diseases,
including cancers and neurodegenerative disorders. Emerging evidence indicates
involvement of RNA-binding proteins (RBPs) in DDR. However, functions of RBPs in
the DDR pathway remain elusive. We have shown previously that the RNA-binding
protein RBM14 is required for non-homologous end joining (NHEJ). Here we show
that RBM14 is required for efficient recruitment of XRCC4 and XLF to chromatin
and the release of KU proteins from chromatin upon DNA damage. Failure of this
process leads to accumulation of double-strand breaks (DSBs) in cells. Thus RBM14
plays crucial role in regulation of NHEJ upon DNA damage.
PMID- 28426350
TI - Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients
With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus
Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.
AB - Purpose The standard treatment of patients with diffuse large B-cell lymphoma
(DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin,
vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent,
has shown activity in DLBCL. This randomized phase III trial compared
lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL
who achieved a complete response (CR) or partial response (PR) to R-CHOP
induction. Methods Patients with previously untreated DLBCL or other aggressive B
cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of
R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo
for 21 days of every 28-day cycle for 24 months. The primary end point was
progression-free survival (PFS). Results A total of 650 patients were randomly
assigned. At the time of the primary analysis (December 2015), with a median
follow-up of 39 months from random assignment, median PFS was not reached for
lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95%
CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups
(eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3,
age younger than 70 v >= 70 years), response (PR v CR) after R-CHOP, and positron
emission tomography status at assignment (negative v positive). With longer
median follow-up of 52 months (October 2016), overall survival was similar
between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common
grade 3 or 4 adverse events associated with lenalidomide versus placebo
maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%),
respectively. Conclusion Lenalidomide maintenance for 24 months after obtaining a
CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.
PMID- 28426351
TI - The absence of crossovers on chromosome 4 in Drosophila melanogaster:
Imperfection or interesting exception?
AB - Drosophila melanogaster chromosome 4 is an anomaly because of its small size,
chromatin structure, and most notably its lack of crossing over during meiosis.
Earlier ideas about the absence of crossovers on 4 hypothesize that these unique
characteristics function to prevent crossovers. Here, we explore hypotheses about
the absence of crossovers on 4, how these have been addressed, and new insights
into the mechanism behind this suppression. We review recently published results
that indicate that global crossover patterning, in particular the centromere
effect, make a major contribution to the prevention of crossovers on 4.
PMID- 28426352
TI - The "risky" reading strategy revisited: New simulations using E-Z Reader.
AB - Eye-movement studies have demonstrated that, relative to college-aged readers,
older readers of alphabetic languages like English and German tend to read more
slowly, making more frequent and longer fixations and longer saccades, and
skipping more words, but also making more frequent regressions. These findings
have led to suggestions that older readers either adopt a "risky" strategy of
using context to "guess" words as a way of compensating for slower rates of
lexical processing, or have a smaller and more asymmetrical perceptual span.
Unfortunately, neither of these hypotheses seemingly explains more recent
observations that older readers of Chinese seem to adopt a more "conservative"
strategy, making shorter saccades and skipping less often. In this paper, we use
the E-Z Reader model of eye-movement control to examine several possible accounts
of the differences between college-aged and older readers of both alphabetic and
non-alphabetic languages. These simulations re-confirm that the "risky" strategy
may be sufficient to explain age-related differences in reader's eye movements,
with older readers of English versus Chinese being, respectively, more versus
less inclined to guess upcoming words. The implications of these results for
aging, reading, and models of eye-movement control are discussed.
PMID- 28426353
TI - Potential Risks of Ecological Momentary Assessment Among Persons Who Inject
Drugs.
AB - BACKGROUND: Ecological momentary assessment (EMA)-which often involves brief
surveys delivered via mobile technology-has transformed our understanding of the
individual and contextual micro-processes associated with legal and illicit drug
use. However, little empirical research has focused on participant's perspective
on the probability and magnitude of potential risks in EMA studies. OBJECTIVES:
To garner participant perspectives on potential risks common to EMA studies of
illicit drug use. METHODS: We interviewed 38 persons who inject drugs living in
San Diego (CA) and Philadelphia (PA), United States. They completed simulations
of an EMA tool and then underwent a semi-structured interview that systematically
explored domains of risk considered within the proposed revisions to the Federal
Policy for the Protection of Human Subjects or the "Common Rule." Interviews were
transcribed verbatim and coded systematically to explore psychological, physical,
social, legal, and informational risks from participation. RESULTS: Participants
perceived most risks to be minimal. Some indicated that repetitive questioning
about mood or drug use could cause psychological (i.e., anxiety) or behavioral
risks (i.e., drug use relapse). Ironically, the questions that were viewed as
risky were considered motivational to engage in healthy behaviors. The most cited
risks were legal and social risks stemming from participant concerns about data
collection and security. IMPORTANCE: Improving our understanding of these issues
is an essential first step to protect human participants in future EMA research.
We provide a brief set of recommendations that can aid in the design and ethics
review of the future EMA protocol with substance using populations.
PMID- 28426354
TI - "It Goes on Everywhere": Injection Drug Use in Canadian Federal Prisons.
AB - BACKGROUND: International and Canadian research on in-prison injection drug use
has documented the frequency of its occurrence as well as some of the resulting
consequences such as increased prevalence of HIV and hepatitis C virus. Access to
prison-based harm reduction programing is thus important. OBJECTIVES: The aim of
this study was to learn from former prisoner experiences and insights on in
prison injection drug use in order to advance and improve access to harm
reduction options, in particular prison-based needle and syringe programs
(PNSPs). METHODS: The qualitative and community-based study was conducted in
2014/2015 and included former prisoners from Ontario, Canada (N = 30) who had
recent experience of incarceration in a federal prison and knowledge of injection
drug use. Data analysis followed the deductive approach, drawing on the expertise
of the academic and community-based research team members. RESULTS: Interview and
focus group participants disclosed that drugs are readily available in Canadian
federal prisons and that equipment used to inject is accessed in a variety of
ways, sometimes gained through illicit means and sometimes made by prisoners
themselves. Equipment sharing is a frequent occurrence, and disposal of such
supplies is rare. Conclusions/Importance: While not yet available in Canada,
PNSPs have led to positive outcomes in international contexts, including
reductions in needle sharing and transmission of HIV and hepatitis C. Support for
PNSPs among numerous Canadian organizations and associations, along with a recent
change in government, could suggest a renewed opportunity for PNSP
implementation.
PMID- 28426355
TI - Income Levels and Response to Contingency Management for Smoking Cessation.
AB - BACKGROUND: Contingency management (CM) has demonstrated its efficacy in treating
many drug addictions, including nicotine. However, one of the most commonly
perceived limitations with regard to its dissemination into community settings is
whether this protocol could be equally effective for treating patients across
different income levels. OBJECTIVE: This study aimed to examine whether
individuals' income levels affect treatment success in a cognitive behavioral
treatment (CBT) that included a voucher-based CM protocol for smoking cessation.
METHODS: A total of 92 treatment-seeking smokers in a community setting were
randomly assigned to a CBT group (N = 49) or to a CBT plus CM group (N = 43). The
CM procedure included a voucher program through which smoking abstinence was
reinforced on a schedule of escalating magnitude of reinforcement with a reset
contingency. We analyzed the impact of self-reported monthly income, alone and in
combination with treatment condition, on short-term (treatment retention) and
long-term (self-reported number of days of continuous smoking abstinence at 6
month follow-up) results. RESULTS: Income had no effect on treatment retention
and continuous abstinence outcomes at 6-month follow-up in either treatment
condition. Treatment modality emerged as the only significant predictor of
treatment success. CONCLUSIONS: Our findings suggest that treatment-seeking
smokers from the general population respond equally well to CM regardless of
their income levels. The results of this randomized controlled trial support the
generalizability of this evidenced-based program into community settings.
PMID- 28426356
TI - Focus Group Findings of Smoking Onset Among Male Youth in China.
AB - BACKGROUND: Adolescence is associated with smoking initiation among men in China.
The lack of qualitative studies using Chinese adolescent samples can pose
challenges to enacting effective smoking prevention messages that resonate with
male Chinese teenagers' thoughts, needs, and wishes. OBJECTIVE: This focus group
study was designed to obtain in-depth contextual information on early smoking
among male teenagers in China. METHODS: Twenty focus groups of 7-10 male students
from vocational and junior colleges (N = 165) were conducted, approximately half
in Shanxi and half in Guangdong. RESULTS: A large number of early smoking
activities occurred in homes and schools, and teenagers considered school toilets
and dorms safe havens for smoking. Many participants' first cigarettes were
offered to them by peers, others first smoked during social interactions, and
some started smoking of their own volition. Teenagers were curious about the
attributes of cigarette products, smoking techniques, and physical reactions.
More participants disclosed negative first smoking experiences than positive
experiences. Negative first physical experiences motivated some participants to
acquire better smoking techniques. Smoking experimentation was sustained in part
by reciprocated cigarette offers. Heavy experimentation occurred before
graduation from high school. Conclusions/Importance: The current findings provide
an empirical basis for developing intervention strategies that are alternative or
complementary to the current conventional health education. These strategies
include cognitive response methods to enhance antismoking beliefs, smoke-free
social interaction norms, and school-based (e.g., peer education) and home-based
(e.g., involving family members) intervention programs.
PMID- 28426357
TI - A Qualitative Assessment of Alcohol Consumption and Sexual Risk Behaviors Among
Men Who Have Sex With Men and Transgender Women in Peru.
AB - BACKGROUND: Peruvian men who have sex with men (MSM) and transgender women (TGW)
experience the double burden of a highly concentrated HIV epidemic with a high
prevalence of alcohol use disorders (AUDs). Recent research has associated both
with risky sexual behaviors, including unprotected sex, having multiple sexual
partners, engaging in sex work, having recent sexually transmitted infections,
and having HIV-infected partners. AUDs have also been associated in MSM/TGW with
being unaware of HIV+ status. OBJECTIVES: This study aims to further examine
issues associated with alcohol consumption, HIV infection, and risk behaviors in
a qualitative analysis of focus groups conducted with MSM/TGW in Peru. METHODS: A
total of 26 MSM/TGW participants with AUDs participated in three semi-structured
focus groups in Lima, Peru. Content analysis was facilitated by software, and
specific themes were elucidated. RESULTS: Participants described their drinking
patterns, including the types of alcoholic drinks they consumed. They depicted
drinking frequently and over multiple-day sessions. Problematic drinking
behaviors were described, as well as the perceived characteristics of alcohol
dependence. Interestingly, HIV-infected participants who were prescribed
antiretroviral therapy did not believe that their drinking affected their
medication adherence. These insights can aid in the design of future
interventions aiming to reduce problematic drinking as well as HIV-related risk
behaviors and, subsequently, HIV incidence. CONCLUSIONS: Peruvian MSM/TGW exhibit
problematic drinking, which may be associated with risky sexual behaviors and HIV
transmission. Interest in reducing alcohol consumption was high, suggesting the
need for targeted behavioral and pharmacological interventions.
PMID- 28426359
TI - Reductions in Hard Drug Use Among Homeless Youth Receiving a Strength-Based
Outreach Intervention: Comparing the Long-Term Effects of Shelter Linkage Versus
Drop-in Center Linkage.
AB - OBJECTIVES: The current study sought to test hard drug use outcomes for youth
receiving a strengths-based outreach and advocacy intervention that linked youth
to either a shelter or a drop-in center. METHODS: Homeless youth (14-24 years
old) were engaged by research assistants (RAs) at soup kitchens, parks,
libraries, and other locations that homeless youth were known to frequent. Youth
were randomly assigned to receive six months of advocacy that focused on linking
youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). Follow-up
assessments were conducted at 3, 6, and 9 months post-baseline. Hard drug use
over time was the main outcome. Intervention condition and service connection
were used as predictors for the baseline level and the slope of change in hard
drug use over time. Data analysis was conducted with Bernoulli Hierarchical
Generalized Linear Modeling in HLM7. RESULTS: The current study found that those
who were in the drop-in linkage condition exhibited a greater reduction in their
odds of using hard drugs during the follow-up points than their counterparts in
the shelter linkage condition. And finally, those who utilized services more
often during the follow-ups were those who exhibited less hard drug use at
baseline and less reduction in their odds of using hard drugs. CONCLUSIONS: This
study suggests that drop-in centers, which are often characterized by low-demand
programming and few behavioral restrictions, are effective for addressing hard
drug use among homeless youth.
PMID- 28426358
TI - Effects of Workplace Generalized and Sexual Harassment on Abusive Drinking Among
First Year Male and Female College Students: Does Prior Drinking Experience
Matter?
AB - BACKGROUND: Workplace harassment, a known risk factor for adult drinking, is
understudied in college samples, but may help explain observed gender differences
in drinking patterns. OBJECTIVE: We examine effects of sexual and generalized
workplace harassment on changes in drinking behavior over the first semesters of
college, and the extent to which these effects differ based on prematriculation
drinking for men and women students. METHOD: Data derive from two waves of a
longitudinal study of eight Midwestern colleges and universities. Data were
collected from 2080 employed students via a Web-based survey assessing sexual and
generalized workplace harassment, stressful life events, drinking to
intoxication, and binge drinking prior to freshman year (fall 2011) and
approximately one year later (summer to fall 2012). At baseline, lifetime
drinking status, frequency of alcohol consumption, and demographics were also
assessed. RESULTS: Linear-mixed modeling indicated that employed women students
who were frequent drinkers prematriculation were at risk for high levels of
drinking associated with workplace harassment, while men who were nondrinkers
were most at risk of increasing problem drinking over time when exposed to
workplace harassment. CONCLUSIONS: Alcohol use prevention efforts directed
towards employed students are needed both prior to and during college, to
instruct students how to identify workplace harassment and cope in healthier ways
with stressful workplace experiences. These efforts might be particularly useful
in stemming problematic drinking among women who drink frequently prior to
college, and preventing men who are nondrinkers upon college entry from
initiating problematic drinking during subsequent enrollment years.
PMID- 28426360
TI - Pharmaceutical Cognitive Enhancement in Greek University Students: Differences
Between Users and Non-Users in Social Cognitive Variables, Burnout, and
Engagement.
AB - Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of
prescribed medication for the improvement of cognitive functioning and academic
performance. Although there are some studies about PCE prevalence, it is less
clear how users and non-users of PCE substances differ with respect to their
positive and negative student experiences (e.g. academic burnout and engagement
with studies) and in social cognitive variables that relate to decision-making
and self-regulation of PCE use. The present study assessed whether students with
different experiences of PCE substance use displayed differences in academic
burnout, study engagement, and social cognitive variables relevant to PCE use.
Three hundred and forty-seven university students (mean age (M) = 22.15 years, SD
= 1.69; 54% females) completed a battery of anonymous questionnaires on academic
burnout, engagement with studies, social cognitive variables relevant to PCE use,
and self-reported use of PCE substances and non-prescribed nutritional
supplements. Three user groups emerged, namely non-users (51.9%, n = 180), single
users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of
both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate
analysis of variance indicated significant differences among the three user
groups in intentions, attitudes, social norms, and anticipated regret toward PCE
use. No significant differences were observed with respect to academic burnout
and work engagement. The findings show that university students may engage in PCE
use independent of their student experiences. Rather, a chemically assisted
performance enhancement mindset seems to differentiate users from non-users of
PCE substances.
PMID- 28426362
TI - Predicting Change in an Integrated Dual Diagnosis Substance Abuse Intensive
Outpatient Program.
AB - Research on routine outcome monitoring in psychotherapy settings is plentiful but
not without implementation obstacles. In fact, there is a relative dearth of real
time outcome monitoring in substance use treatment settings. Numerous barriers to
the development and implementation of clinical decision support tools and outcome
monitoring of substance use patients, including the need to establish expected
trajectories of change and use of reliable change indices have been identified
(Goodman, McKay, & DePhilippis, 2013 ). The current study was undertaken to
develop expected trajectories of change and to demonstrate the treatment
effectiveness of a dual diagnosis intensive outpatient program. The expected
trajectories of change for days of substance use and depression scores were
developed using predictive equation models from derivation samples and then
applied to cross-validation samples. Predictive equations to monitor substance
use were developed and validated for all patients and for only patients who were
actively using substance at the time of admission, as well as to monitor severity
of their depression symptom on a weekly basis. Validation of the equations was
assessed through the use of Cohen's kappa (kappa), receiver operating
characteristic curves, reliable change index, and percentage improvement. Large
effect sizes for reductions in substance use (Cohen's d = .76) and depressive
symptoms (d = 1.10) are reported. The best predictive models we developed had
absolute accuracy rates ranging from 95 to 100%. The findings from this study
indicate that predictive equations for depressive symptoms and days of substance
use can be derived and validated on dual diagnosis samples.
PMID- 28426361
TI - Sociodemographic and Substance Use Disorder Determinants of HIV Sexual Risk
Behavior in Men and Women in Outpatient Drug Treatment in the NIDA National Drug
Abuse Treatment Clinical Trials Network.
AB - BACKGROUND: Sexual risk behavior is now the primary vector of HIV transmission
among substance users in the United States with gender as a crucial moderator of
risk behavior. OBJECTIVES: The purpose of this study was to examine gender
differences in factors (age, race/ethnicity, education) that predict main-partner
unprotected sexual occasions (USO) using the unique platform of two parallel NIDA
National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex
intervention trials. METHODS: Baseline assessments of male (N = 430) and female
(N = 377) participants included demographic characteristics; past 3-month sexual
activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid
use disorders. Using mixed effects generalized linear modeling of the main
outcome USO, two-way interactions of gender with age, race/ethnicity, and
education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid
use disorder. RESULTS: When adjusted for alcohol use disorder, the interaction of
education and gender was significant. For men, a high school or greater education
was significantly associated with more USO compared to men with less than high
school. For women, greater than high school education was significantly
associated with less USO compared to women with a high school education. None of
the other interactions were significant when adjusted for cocaine/stimulant or
opioid use disorder. Conclusions/Importance: This study demonstrates gender
differences in the relationship of education, alcohol use disorder, and main
partner USO in individuals in substance abuse treatment. This underscores the
importance of considering demographic and substance use factors in HIV sexual
risk behavior and in crafting prevention messages for this population.
PMID- 28426363
TI - Social Risk and Protective Factors in Adolescents' Reduction and Cessation of
Alcohol Use.
AB - BACKGROUND: Adolescents' alcohol use is related to many health problems,
injuries, and violent acts, some with fatal consequences. A gap exists in the
literature discussing risk/protective factors in change from non-heavy drinking
to non-drinking, and also for change from heavy drinking to non-heavy drinking or
non-drinking. OBJECTIVE: This secondary study examined some risk and protective
factors involved when adolescent non-heavy drinkers and adolescent heavy drinkers
curb or terminate their drinking. METHOD: The temporal-ordered analysis evaluated
570 nonheavy drinkers and 374 heavy drinkers (all adolescents), a sample
extracted from Wave 1 and Wave 2 of the National Longitudinal Study of Adolescent
to Adult Health, or Add Health. RESULTS: We observed positive associations
between likelihood of change from heavy/non-heavy drinking to nondrinking and 5
characteristics: neighborhood attachment, maternal receipt of public assistance,
African American ethnicity, maternal involvement, physical maltreatment,
depressive feelings, and substance-abuse treatment. We observed negative
associations between this outcome and peer drinking, delinquent behaviors, drug
use, and emotional maltreatment. Positive associations were found between
likelihood of change from heavy drinking to non-heavy drinking and both maternal
involvement and depressive feelings, while a negative association was found
between this outcome and delinquent behaviors. CONCLUSIONS: Reduction/cessation
interventions should, at the individual level, focus on ending adolescent
drinkers' associations with alcohol-using and delinquent peers. Interventions
require supportive roles for parents, schools, and communities.
PMID- 28426365
TI - Moderators of the Effects of Alcohol Protective Behavioral Strategies: Three
Attempts of Replication and Extension.
AB - BACKGROUND: Protective behavioral strategies (PBS) can be used to reduce alcohol
related harm when drinking. Despite much research demonstrating that use of
protective behavioral strategies (PBS) is associated with decreased alcohol
use/problems, few studies have examined moderators of these associations.
Moderation tests are important as they define the boundary conditions of the
protective effects of PBS use (i.e., identify for whom and in what context PBS
use reduces harm). OBJECTIVES: We aimed to replicate and extend the findings from
three published studies that have examined putative moderators of PBS-alcohol
associations: self-regulation, negative urgency, and drinking refusal self
efficacy. METHOD: Participants were recruited from a psychology department
participant pool at a large, southwestern university in the United States (N =
628). RESULTS: Although we replicated most main effects and bivariate
correlations, we failed to replicate any of the moderation effects (i.e.,
interaction effects). Conclusions/Importance: We urge PBS researchers to attempt
to replicate moderation effects in independent samples to determine these
effects' reproducibility. Limitations and future directions are discussed.
PMID- 28426364
TI - Patterns of Mood and Personality Factors and Associations With STI/HIV-Related
Drug and Sex Risk Among African American Male Inmates.
AB - BACKGROUND: Research on the association between antisocial personality disorder
(ASPD) with comorbid mental disorders and sexually transmitted infection
(STI)/HIV risk among inmates is scant despite the high prevalence of
psychopathology and of STI/HIV in this population. METHODS: We used baseline data
from Project DISRUPT, a cohort study conducted among incarcerated African
American men (n = 207), to measure associations between ASPD and STI/HIV risk. We
also conducted latent class analyses (LCAs) to identify subgroups defined by ASPD
with comorbid stress, depression, and borderline personality disorder symptoms
and measured associations between latent class membership and STI/HIV risk.
RESULTS: Approximately 15% had ASPD and 39% reported depression. Controlling for
sociodemographics, stress, and depression, ASPD was independently associated with
illicit [AOR = 3.23, 95% confidence interval (CI): 1.18-8.87] and injection drug
use (AOR: 5.49, 95% CI: 1.23-24.42) but not with sexual risk. LCAs suggested that
those at high risk of ASPD were likely to experience co-morbid mental disorders.
ASPD comorbid with these disorders was linked to drug and sex risk. CONCLUSIONS:
STI/HIV prevention for inmates should incorporate diagnosis and treatment of ASPD
and comorbid disorders, and interventions to address ASPD-related factors (e.g.,
impulsivity) that drive STI/HIV risk.
PMID- 28426366
TI - Notch1 induces endothelial senescence and promotes tumor progression.
PMID- 28426367
TI - Child and Adolescent Emergency and Urgent Mental Health Delivery Through
Telepsychiatry: 12-Month Prospective Study.
AB - BACKGROUND: The significant gap between children and adolescents presenting for
emergency mental healthcare and the shortage of child and adolescent
psychiatrists constitutes a major barrier to timely access for psychiatric
assessment for rural and remote areas. Unlike remote areas, urban emergency
departments have in-house psychiatric consultation. Telepsychiatry may be a
solution to ensure the same service for remote areas. However, there is a paucity
of studies on the use of telepsychiatry for child and adolescent emergency
consults. Thus, the aim of our study was to (1) assess patient satisfaction with
telepsychiatry and (2) compare clinical characteristics and outcome of
telepsychiatry with face-to-face emergency child and adolescent assessments.
METHODS: This is a prospective study of telepsychiatry emergency assessments of
children and adolescents referred by emergency physicians. The comparison group
was age- and gender-matched patients seen for face-to-face urgent assessments.
Data were gathered on demographic and clinical variables. Telepsychiatry
satisfaction was assessed using a questionnaire. Descriptive statistics and chi
square tests were used to assess group differences for each variable. Logistic
regression was used to assess impact of the variables on outcome after the
consult. A p value <0.05 was used to determine statistical significance. RESULTS:
Sixty (n = 60) assessments were conducted through telepsychiatry in 12 months.
Among the telepsychiatry group, Aboriginal patients were over-represented (50%
vs. 6.7%, p < 0.001), a higher proportion received a diagnosis of adjustment
disorder (22% vs. 8.3%, p = 0.004) or no diagnosis (27% vs. 6.7%, p = 0.004)
compared with controls. There was no statistically significant difference between
groups on other clinical variables. Patients reported a high degree of
satisfaction with telepsychiatry. CONCLUSIONS: Telepsychiatry is acceptable to
patients and families for safe emergency assessment and follow-up, reducing
unnecessary travel to urban centers. Longer time outcomes are needed to establish
validity of telepsychiatry for emergency assessments.
PMID- 28426368
TI - Living in the epilepsy treatment gap in rural South India: A focused ethnography
of women and problems associated with stigma.
AB - In India, women with epilepsy face unique challenges. A focused ethnography of
six women within the epilepsy treatment gap was conducted in rural South India.
Women were asked to describe their day-to-day lives. Data were collected through
open-ended, semistructured interview questions, participant observation, and
field notes. Thematic analysis was done. The disease-related stigma contributed
to the women's physical, psychological, and emotional struggles; the women and
their family members made every effort to conceal the disease. Educational
interventions to create awareness could help women seek effective treatments for
their seizures, thereby reducing the stigma and improving the quality of their
lives.
PMID- 28426370
TI - PIN-formed protein, a door to reveal the mechanism for auxin-triggered initiation
of cotton fiber.
AB - Cotton fibers are differentiated ovule epidermal cells that provide an ideal
model to study cell differentiation and elongation. Establishment of auxin
maximum in fiber cells is crucial for cotton-fiber protrusion from ovule surface.
However, it is unclear where the auxin originates from and how the auxin
accumulates in fiber cells. Our recent results indicate that the auxin is mainly
imported from the outside of ovules, and transported to fiber cells through GhPIN
(homolog of PIN-formed proteins in cotton) -mediated polar auxin transport,
rather than in situ synthesis. Based on our finding in GhPINs, we discuss here
briefly how auxin flow to fiber cells and auxin gradient in ovule epidermis is
established mainly by GhPIN3a protein.
PMID- 28426369
TI - HOS1 acts as a key modulator of hypocotyl photomorphogenesis.
AB - Plants recognize light as an environmental signal to determine the proper timing
of growth and development. In Arabidopsis seedlings, hypocotyl growth is promoted
in the dark but suppressed in the light. It is known that the red/far-red light
sensing receptor phytochrome B (phyB) suppresses the function of PHYTOCHROME
INTERACTING FACTOR (PIF) transcription factors, which act as photomorphogenic
repressors. However, molecular mechanisms underlying the phyB-mediated inhibition
of PIF functioning remain unclear. We recently demonstrated that HIGH EXPRESSION
OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) facilitates the phyB-mediated
suppression of PIF4 during the light period to achieve hypocotyl
photomorphogenesis. HOS1 inhibits the transcriptional activation activity of PIF4
by forming protein complexes. Notably, phyB-mediated light signals induce HOS1
activity, thus promoting hypocotyl photomorphogenesis. While HOS1 is known to act
as an E3 ubiquitin ligase or a chromatin remodeling factor, our data illustrate a
novel role of HOS1: it acts as a component of phyB-mediated light signaling in
hypocotyl photomorphogenesis.
PMID- 28426372
TI - Continuing Education-"The Action Level"(r).
AB - Access "The Action Level"(r) Questions online at:
http://www.acgih.org/products/joeh/alquestions.htm Access "The Action Level"(r)
Answers online at: http://www.acgih.org/products/joeh/alanswers.htm Access "The
Action Level"(r) Registration Form online at:
https://www.acgih.org/products/joeh/alregfrm.htm "The Action Level,"(r) a self
study, continuing education program, provides a convenient and interesting
opportunity for individuals to expand their knowledge in relevant areas of
industrial hygiene, as well as occupational and environmental safety and health.
The program is approved by both the American Board of Industrial Hygiene, and the
Board of Certified Safety Professionals, which award Certification Maintenance
(CM) points and Continuance of Certification (COC) points, respectively, for
successful participation. Participants must read each issue of the Journal,
answer "The Action Level"(r) questions, and return the completed answer sheet at
the end of that issue's "The Action Level"(r) column. To earn the designated CM
or COC credit, a score of 70 percent or better is required within a 12-month
period. Certified Industrial Hygienists and Certified Associate Industrial
Hygienists may earn 2 points per year. Certified Safety Professionals may earn
1.2 points per year. Enrollment is possible each month, but points are awarded
only four times each year-in March, June, September, and December-to participants
who score an average of 70 percent or better within each three-month period. If
you register in September 2009, you will not receive CM points and/or COC points
until the following quarter. In the next quarter, you'll receive 0.5 CM points
and/or 0.3 COC points after satisfactorily completing answer sheets for the
October, November and December 2009 issues, and so on. To enroll, complete the
registration form and the answer sheet at the end of this "The Action Level"(r)
column. The cost is $199 (ACGIH(r)/AIHA members)/$219 (nonmembers) for one year.
Nonmembers are encouraged to become members to take advantage of the member
discount. For more information regarding ACGIH(r) membership, call 513-742-2020,
or apply on-line at http://www.acgih.org/members/memberform.htm . Checks must be
in U.S. currency, drawn on a U.S. bank, and payable to ACGIH(r). We also accept
AmEx, MasterCard, Discover and Visa. This continuing education program fee is
separate from the Journal subscription cost. The fee covers administration costs,
and is nonrefundable. Submissions must be received by the date listed on each
answer sheet.
PMID- 28426371
TI - * Optimization of Preculture Conditions to Maximize the In Vivo Performance of
Cell-Seeded Engineered Intervertebral Discs.
AB - The development of engineered tissues has progressed over the past 20 years from
in vitro characterization to in vivo implementation. For musculoskeletal tissue
engineering in particular, the emphasis of many of these studies was to select
conditions that maximized functional and compositional gains in vitro. However,
the transition from the favorable in vitro culture environment to a less
favorable in vivo environment has proven difficult, and, in many cases,
engineered tissues do not retain their preimplantation phenotype after even short
periods in vivo. Our laboratory recently developed disc-like angle-ply structures
(DAPS), an engineered intervertebral disc for total disc replacement. In this
study, we tested six different preculture media formulations (three serum
containing and three chemically defined, with varying doses of transforming
growth factor beta3 [TGF-beta3] and varying strategies to introduce serum) for
their ability to preserve DAPS composition and metabolic activity during the
transition from in vitro culture to in vivo implantation in a subcutaneous
athymic rat model. We assayed implants before and after implantation to determine
collagen content, glycosaminoglycan (GAG) content, metabolic activity, and
magnetic resonance imaging (MRI) characteristics. A chemically defined media
condition that incorporated TGF-beta3 promoted the deposition of GAG and collagen
in DAPS in vitro, the maintenance of accumulated matrix in vivo, and minimal
changes in the metabolic activity of cells within the construct. Preculture in
serum-containing media (with or without TGF-beta3) was not compatible with DAPS
maturation, particularly in the nucleus pulposus (NP) region. All groups showed
increased collagen production after implantation. These findings define a
favorable preculture strategy for the translation of engineered discs seeded with
disc cells.
PMID- 28426373
TI - Immortal Life of the Common Rule: Ethics, Consent, and the Future of Cancer
Research.
PMID- 28426374
TI - Perioperative Hepatic Arterial Infusion Pump Chemotherapy Is Associated With
Longer Survival After Resection of Colorectal Liver Metastases: A Propensity
Score Analysis.
AB - Purpose To investigate whether perioperative hepatic arterial infusion pump
chemotherapy (HAI) was associated with overall survival (OS) in patients who had
a complete resection of colorectal liver metastases (CLM). Methods Patients who
underwent a complete resection of CLM between 1992 and 2012 were included from a
single-center prospectively maintained database. All patients who received HAI
also received perioperative systemic chemotherapy. Propensity score analysis was
used to match patients for seven known prognostic factors. Results A total of
2,368 consecutive patients underwent a complete resection of CLM, with a median
follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67
months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced
disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For
patients who received modern systemic chemotherapy (n = 1,442), the median OS was
67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio
adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59
to 0.76; P < .001). A pronounced difference in median OS was found for patients
with node-negative colorectal cancer (129 months with HAI v 51 months without; P
< .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53
months without; P < .001). Conclusion Patients who received HAI had a median OS
of approximately 2 years longer than patients without HAI. The strong association
was independent of the use of modern systemic chemotherapy and remained in
propensity score analysis. Patients with node-negative primary tumors or a low
clinical risk score seemed to benefit most from HAI.
PMID- 28426375
TI - United States Population-Based Estimates of Patient-Reported Outcomes Measurement
Information System Symptom and Functional Status Reference Values for Individuals
With Cancer.
AB - Purpose To estimate cancer population-based reference values in the United States
for eight PROMIS (Patient-Reported Outcomes Measurement Information System)
domains by age and stage of disease. Patients and Methods For the Measuring Your
Health (MY-Health) study, persons newly diagnosed with cancer (prostate,
colorectal, non-small-cell lung, non-Hodgkin lymphoma, breast, uterine, or
cervical) from 2010 to 2012 (N = 5,284) were recruited through the National
Cancer Institute's SEER Program. Participants were mailed surveys 6 to 13 months
after diagnosis. Raking by race/ethnicity, age, and stage generated weighted
average PROMIS scores for pain interference, fatigue, anxiety, depression, sleep
disturbance, physical function, ability to participate in social roles, and
cognitive function. PROMIS measures are standardized to a T-score metric, with a
score of 50 representing the general US population mean. Clinically meaningful
differences were defined as a 3-point difference in scores. Results Several
reference values (means) for patients with cancer were worse than the general
United States population norms of 50. These include pain interference (52.4),
fatigue (52.2), and physical function (44.1). Reference values were highest (ie,
showed greatest symptom burden) in lung cancer (pain interference, 55.5; fatigue,
57.3; depression, 51.4) and cervical cancer (anxiety, 53.2; sleep disturbance,
53.4). Reference values for patients age 65 to 84 years reported lower sleep
disturbance, anxiety, and depression, and better cognitive function than younger
patients. Cancer reference values were poorer among those with advanced disease
compared with patients with limited or no evidence of disease, specifically
physical function (41.1 v 46.6, respectively), fatigue (55.8 v 50.2,
respectively), and pain interference (55.2 v 50.9, respectively). Conclusion In a
large, population-based sample of patients with recently diagnosed cancer, we
observed symptom severity and functional deficits by age, stage, and cancer type
consistent with the expected impact of cancer diagnosis and treatment. These
United States cancer reference values can help facilitate interpretation of the
PROMIS domain scores in research studies or in clinical applications that measure
and evaluate the symptom and functional burden patients with cancer experience
after initial treatment.
PMID- 28426376
TI - Evaluation of Different Laser-Supported Surgical Protocols for the Treatment of
Oral Leukoplakia: A Long-Term Follow-Up.
AB - PURPOSE: The aim of this study was to evaluate the long-term success rate of oral
leukoplakia treatments by using different laser-supported surgical protocols.
PATIENTS AND METHODS: Overall, 2347 diagnosed homogeneous oral leukoplakias were
treated with CO2 laser and were included in this study. Different surgical
protocols (P) were used: P1 (SV = superficial scanning) was a complete
superficial vaporization of the leukoplakia by a scanning mode in two passages
respecting an overlapping. Only the visible white area was treated in one
surgical session independently of the lesion size. P2 (CR1x1) was a complete
excision of the lesions until a tissular depth of 1 mm and 1 mm of surrounding
healthy-like tissue were attained. The visible white area was treated in one
surgical session independently of the lesion size. P3 (CR1x3) was a complete
excision of the lesions until a minimum tissue depth of 1 mm and 3 mm of
surrounding healthy-like tissue were obtained. The visible white area was treated
in one surgical session independently of the lesion size. P4 (PR1x3) was similar
to the third one, but for patient comfort, the large lesions of leukoplakias
(lesion size higher than 20 mm), the complete surgical excision of the
leukoplakia was performed in multiple sessions that were spaced by 1 month
(partial surgical removal of 10 mm per session). All patients were recalled at 2
and 8 weeks after surgery, and then every 2 months during the first year, every 4
months during the second year, and once a year for the follow-up period of 6
years. A biopsy was done once a year during the follow-up period in the surgical
site when needed. The control consisted of checking the nature and the aspect of
the healed mucosa to exclude an eventual recurrence of leukoplakia. RESULTS: The
percentage of permanent success after 6 years of follow-up was 5.7%, 69.7%,
97.8%, and 71.9%, respectively, for the first surgical protocol (SV), the second
(CR 1 * 1), the third (CR 1 * 3), and the fourth (PR 1 * 3). The appearance of
malignant transformation after laser treatment (during the follow-up period of 6
years) was 20%, 1%, and 0.2%, respectively, for the groups treated by the
following protocols: 1 (SV), 2 (CR 1 * 1), and 4 (PR 1 * 3). Only in the third
group CR1x3, no dysplasia or malignant transformation was noted. On the contrary,
the appearance of malignant transformation in failed treated cases was 21.21% for
the protocol 1 (SV), 3% for the protocol 2 (CR 1 * 1), and 0.6% for the protocol
4 (PR 1 * 3). CONCLUSIONS: The results of this long-term follow-up of treated
patients with oral homogeneous leukoplakias pointed out that the surgical laser
protocol respecting the complete excision of leukoplakias, in one session, by the
removal of a minimum of 1 mm in lesion depth and 3 mm of surrounding healthy-like
tissues (CR 1 * 3) offers significantly the highest success rate.
PMID- 28426377
TI - Development of the Sports Organization Concussion Risk Assessment Tool (SOCRAT).
AB - OBJECTIVE: In this paper, we describe the development of a novel tool-the Sports
Organization Concussion Risk Assessment Tool (SOCRAT)-to assist sport
organizations in assessing the overall risk of concussion at a team level by
identifying key risk factors. METHODS: We first conducted a literature review to
identify risk factors of concussion using ice hockey as a model. We then
developed an algorithm by combining the severity and the probability of
occurrence of concussions of the identified risk factors by adapting a risk
assessment tool commonly used in engineering applications. RESULTS: The following
risk factors for ice hockey were identified: age, history of previous
concussions, previous body checking experience, allowance of body checking, type
of helmet worn and the game or practice environment. These risk factors were
incorporated into the algorithm, resulting in an individual risk priority number
(RPN) for each risk factor and an overall RPN that provides an estimate of the
risk in the given circumstances. CONCLUSION: The SOCRAT can be used to analyse
how different risk factors contribute to the overall risk of concussion. The tool
may be tailored to organizations to provide: (1) an RPN for each risk factor and
(2) an overall RPN that takes into account all the risk factors. Further work is
needed to validate the tool based on real data.
PMID- 28426378
TI - Ostracism and physiological arousal following traumatic brain injury.
AB - PRIMARY OBJECTIVE: This study aimed to examine the psychological and
physiological effects of ostracism in adults with traumatic brain injury (TBI).
RESEARCH DESIGN: A within-subject, counterbalanced design was used. The two
conditions, inclusion and ostracism, were examined across two groups (between
subjects). METHODS AND PROCEDURES: A group of 21 adults with TBI and 17 matched
controls participated in the Cyberball paradigm. This task is a computerised task
that exposes participants to a game of catch and throw. In the inclusion
condition they are included fairly in the game, while in the ostracism condition
they are excluded from the game following the first few throws. Skin conductance
levels (SCLs) were measured throughout the game as a proxy for social stress.
MAIN OUTCOMES: Results showed that people with TBI were cognitively aware of when
they are being ostracised, but that their self-reported emotional experience to
social exclusion was different to that of the control group. Differences in SCLs
between groups and between conditions did not reach significance nor did they
correlate with behavioural responses. CONCLUSIONS: These findings are discussed
in terms of the consequences of dissociation between psychological and
physiological responses and the implications for motivating behaviours associated
with re-inclusion.
PMID- 28426380
TI - The Henry Stonnington Award for best review paper published in Brain Injury 2016.
PMID- 28426381
TI - Hyperbaric oxygen for experimental intracerebral haemorrhage: Systematic review
and stratified meta-analysis.
AB - OBJECTIVE: Hyperbaric oxygen (HBO) is widely used in treating various
neurological diseases. However, HBO for treatment of intracerebral haemorrhage
(ICH) remains controversial, in either animal or clinical studies. Therefore, we
conducted this systematic review and meta-analysis on studies describing the
efficacy of HBO in animal models of ICH. METHODS: Studies were identified by
searching mainstream databases through November 2015. The efficacy of HBO in
animal models of ICH was assessed by changes in the brain water content (BWC),
neurobehavioural outcome (NO) or both. Subgroup analyses were performed according
to different design characteristics. RESULTS: In total 15 studies met our
inclusion criteria. HBO can reduce the BWC (-0.982, 95% CI, -1.148 to -0.817; P <
0.01; 57 comparisons), and improve NO (-0.767, 95% CI, -1.376 to -0.159; P <
0.01; eight comparisons). HBO was most effective in reducing BWC when given 72 h
after ICH for a 4- to 5-day consecutive treatment at the chamber pressure of 3.0
atmosphere absolute. Efficacy was higher with phenobarbital anaesthesia, the
blood infusion model and in rabbits. CONCLUSION: Although HBO was found to be
effective in experimental ICH, additional confirmation is needed due to possible
publication bias, poor study quality and the limited number of studies conducting
clinical trials.
PMID- 28426382
TI - Effectiveness of hand washing on the removal of iron oxide nanoparticles from
human skin ex vivo.
AB - In this study, the effectiveness of washing with soap and water in removing
nanoparticles from exposed skin was investigated. Dry, nanoscale hematite (alpha
Fe2O3) or maghemite (gamma-Fe2O3) powder, with primary particle diameters between
20-30 nm, were applied to two samples each of fresh and frozen ex vivo human skin
in two independent experiments. The permeation of nanoparticles through skin, and
the removal of nanoparticles after washing with soap and water were investigated.
Bare iron oxide nanoparticles remained primarily on the surface of the skin,
without penetrating beyond the stratum corneum. Skin exposed to iron oxide
nanoparticles for 1 and 20 hr resulted in removal of 85% and 90%, respectively,
of the original dose after washing. In the event of dermal exposure to chemicals,
removal is essential to avoid potential local irritation or permeation across
skin. Although manufactured at an industrial scale and used extensively in
laboratory experiments, limited data are available on the removal of engineered
nanoparticles after skin contact. Our finding raises questions about the
potential consequences of nanoparticles remaining on the skin and whether
alternative washing methods should be proposed. Further studies on skin
decontamination beyond use of soap and water are needed to improve the
understanding of the potential health consequences of dermal exposure to
nanoparticles.
PMID- 28426383
TI - Contribution of sucrose transporters to phloem unloading within Sorghum bicolor
stem internodes.
AB - Sucrose produced in source leaves is loaded into collection phloem, transported
to sinks and unloaded for utilization or storage. In the context of long distance
transport, sucrose transporters (SUTs) can function to load sucrose into
collection phloem, retrieve leaked sucrose during long distance transport, and
load sucrose into sink cells. SUTs have also been proposed to efflux sucrose
under conditions of low proton motive force and low extracellular sucrose. The
involvement of sucrose transporters in phloem unloading in a representative
monocot stem, Sorghum bicolor, was evaluated during different stages of internode
development. Transcript levels and functional properties of selected key
transporters were measured, with both cellular and subcellular localization
determined.
PMID- 28426384
TI - A 2-year-old boy with circulatory failure owing to streptococcal toxic shock
syndrome: case report.
AB - A 2-year-old boy presented with severe hypotension and acute kidney injury after
a prodrome of non-bloody diarrhoea and fever in the preceding 3 days. He had a
mild Ebstein cardiac anomaly but otherwise a normal past history and growth. On
examination, he looked ill, his temperature was 37.5 degrees C, circulation was
poor, and there were several purpuric lesions on the face, hands and scrotum.
Haemoglobin was 7.8 g/dL (11-14), total white cell count 27 * 109/L, platelets 62
* 109/L, blood urea nitrogen 20.7 mmol/L (4.2-17.1), serum creatinine 95.4
MUmol/L (21.2-36.2), CRP 154 mg/L (<5), AST 296 U/L (11-50), ALT 909 U/L (7-40)
and C3 component of complement 0.8 g/L (0.9-1.8). Activated partial
thromboplastin time (APTT) and prothrombin time (PT) were prolonged and
fibrinogen level was 1.0 g/L (2-4). He received immediate fluid resuscitation (IV
0.9% saline solution, 2 * 10 ml/kg boluses, followed by glucose 5/0.45% sodium
chloride solution, 2 * 10 ml/kg) and antibiotics (ciprofloxacin and amikacin) but
circulation continued to deteriorate with development of decreased consciousness.
He was placed on mechanical ventilation and vasopressor agents were added.
Despite improved circulation over the next 2 days, he developed oliguria,
progressive fluid overload, generalised oedema and a right-sided pleural
effusion. Dialysis was commenced on day 3 of admission. Differential diagnosis
included sepsis, atypical haemolytic uraemic syndrome and lupus nephritis. Blood
and urine cultures remained negative but an anti-streptolysin O titre of 1318
(<200) IU/mL led to the diagnosis of streptococcal toxic shock syndrome which is
rare in early childhood and associated with high mortality. Haemodialysis was
commenced and continued for 10 days with successful treatment of fluid overload
and subsequent extubation. Renal function was completely restored over the
following 6 weeks and he was discharged in good clinical condition about 2 months
after intial admission. The clinical course and outcome are discussed, and the
importance of timely initiation of dialysis when there is fluid overload is
emphasised.
PMID- 28426385
TI - Birth in winter can reduce the risk of lung cancer: A retrospective study of the
birth season of patients with lung cancer in Beijing area, China.
AB - The season of birth is an important risk factor for several diseases. We explored
the relationship between birth season and lung cancer. In this population-based
retrospective study, we focused on patients with lung cancer who had registered
at the Beijing Institute for Cancer Research from 2003 to 2012. In total, 33,025
patients were divided into five subgroups based on their histologic
classification, and these five subgroups were compared with the general
population (i.e., the permanent resident population of Beijing in 2013). A binary
logistic regression method with sex and age as control factors was used to
evaluate the relationship between birth season and lung cancer; P < 0.01 was
statistically significant. Taking winter as a reference in our analysis of the
relationship between season of birth and lung cancer, we found that people who
were born in other seasons had a higher probability of developing lung cancer
(spring: odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.03-1.09;
summer: OR = 1.07, 95% CI = 1.04-1.10; autumn: OR = 1.06, 95% CI = 1.03-1.09) (P
< 0.01). Among the five subgroups, persons with squamous cell carcinoma who were
born in summer were more likely to develop lung cancer than those who were born
in winter (OR = 1.09, 95% CI = 1.02-1.15, P = 0.006). The other subgroups showed
no correlation with season of birth (P > 0.01). This study demonstrates that for
people born in winter, the risks of developing lung cancer and squamous cell
carcinoma are comparatively lower than those for people born in other seasons.
Differences in immune function and the maternal nutrition status during pregnancy
of people born in different seasons may explain this finding.
PMID- 28426386
TI - New Zealanders working non-standard hours also have greater exposure to other
workplace hazards.
AB - Exposure to workplace hazards, such as dust, solvents, and fumes, has the
potential to adversely affect the health of people. However, the effects of
workplace hazards on health may differ when exposure occurs at different times in
the circadian cycle, and among people who work longer hours or who do not obtain
adequate sleep. The aim of the present study was to document exposures to
workplace hazards across a national sample of New Zealanders, comparing people
who work a standard 08:00 -17:00 h Monday-to-Friday working week (Std hours) and
those who do not (N-Std hours). New Zealanders (n = 10 000) aged 20-64 yrs were
randomly selected from the Electoral Roll to take part in a nationwide survey of
workplace exposures. Telephone interviews were conducted between 2004 and 2006,
using a six-part questionnaire addressing demographics, detailed information on
the current or most recent job (including exposures to a range of workplace
hazards), sleep, sleepiness, and health status. N-Std hours were categorised on
the basis of: being required to start work prior to 07:00 h or finish work after
21:00 h and/or; having a regular on-call commitment (at least once per week)
and/or; working rotating shifts and/or; working night shift(s) in the last month.
The response rate was 37% (n = 3003), with 22.2% of participants (n = 656)
categorised as working N-Std hours. Industry sectors with the highest numbers of
participants working N-Std hours were manufacturing, health and community
services, and agriculture, fishing, and forestry. Response rate was 37% (n =
3003) with 22.2% (n = 656) categorised as working N-Std hours. Participants
working N-Std hours were more likely to be exposed to all identified hazards,
including multiple hazards (OR = 2.45, 95% CI = 2.01-3.0) compared to those
working Std hours. Participants working N-Std hours were also more likely to
report 'never/rarely' getting enough sleep (OR = 1.38, 95% CI = 1.15-1.65),
'never/rarely' waking refreshed (OR = 1.23, 95% CI = 1.04-1.47), and excessive
sleepiness (OR = 1.77, 95% CI = 1.29-2.42). New Zealanders working N-Std hours
are more likely to be exposed to hazards in the workplace, to be exposed to
multiple hazards, and to report inadequate sleep and excessive sleepiness than
their colleagues working a standard 08:00-17:00 h Monday-to-Friday working week.
More research is needed on the effects of exposure to hazardous substances
outside the usual waking day, on the effects of exposure to multiple hazards, and
on the combination of hazard exposure and sleep restriction as a result of shift
work.
PMID- 28426388
TI - If the Morning-Evening Questionnaire (MEQ) is able to predict the actigraphy
based acrophase, how does its reduced, five-item version (rMEQ) perform?
PMID- 28426387
TI - Characterization of bimodal chronotype and its association with sleep: A
population-based study.
AB - The circadian system coordinates internal events in a daily schedule to make sure
that the body systems are synchronized to environmental time and internal cues.
One important behavioral aspect of the circadian system is the chronotype. It is
usually assessed through subjective questionnaires, being the Horne-Ostberg
Morningness-Eveningness Questionnaire (MEQ) one of the most used. It classifies
individuals into three major categories: morning, evening, and intermediate
types. Recently, it has been hypothesized the existence of a fourth chronotype,
the bimodal type, through an algorithm derived from the MEQ responses. Bimodals
answer as morning-types in some questions, and as evening-types in others,
resulting in an intermediate total score. To better characterize this phenotype,
the present study aimed to detect and characterize the frequency of the bimodal
chronotype in the EPISONO, a large population-based cohort, as well as to verify
the association between bimodality and sleep parameters and genetic variation in
the PER3 gene. Of the 1,042 individuals who participated of the EPISONO, 857 had
MEQ filled correctly. We found that 16% of our sample were bimodal types. We
observed that bimodal individuals were significantly younger and had lower body
mass index. The association between PER3 VNTR genotype and gender with bimodal
chronotype was not significant. However, we found an association between
bimodality and Epworth Sleepiness Scale (EES) and apnea-hypopnea index (AHI). We
did not find a statistically significant difference between bimodals and
intermediate non-bimodals for the studied variables. Lastly, it was observed that
the most significant predictors for bimodal chronotype were female gender, AHI,
and EES. In conclusion, the present work provides more evidence that the bimodal
type might have to be considered when classifying chronotype and its association
with young age and sleepiness may be due to the influence of social and
environmental factors.
PMID- 28426389
TI - Melatonin and circadian rhythms in autism: Case report.
AB - Among the most co-occurring conditions in autism spectrum disorders (ASD), there
are sleep disorders which may exacerbate associated behavioral disorders and lead
to intensification of existing autistic symptoms. Several studies investigating
the use of melatonin in the treatment of sleep disorders in ASD have shown
comparative efficiency in sleep with little or no side effects. Here we report a
case of ASD with non-24-hour rhythm and the effect of melatonin in circadian
parameters by actigraphy. Visual analysis of the first 10 days recorded and the
periodogram suggest that this patient showed a non-24-hour rhythm. This ASD
subject showed before melatonin administration an activity/rest rhythm lower than
24 hours. The results show that melatonin increased approximately 4.7 times the
regularity of circadian activity rhythm and resting staying on average between
00:00 and 06:00 and showed positive effects in improving the quality of sleep and
behavior. So, the actigraphy showed an ASD subject with a non-24-hour
activity/rest rhythm which changed this rhythm to a 24-hour rhythm after
melatonin administration. This result reinforces the prospect of therapy with
melatonin for synchronization (increased regularity) of endogenous rhythms and
improve sleep quality and hence behavior and indicates the actigraphy as a choice
tool to characterize several parameters of the activity/rest rhythm of ASD
individuals.
PMID- 28426393
TI - A Systematic Literature Review of Experiences of Professional Care and Support
Among People Who Self-Harm.
AB - Self-harm is an increasing phenomenon among young people, with potentially fatal
outcomes. Patient's perceptions of treatment and support are poorly documented.
The aim was to synthesise the experiences of those who self-harm, with special
reference to professional care and support by family, friends, and the school
system. A systematic review of the literature was conducted. Following retrieval
of 1,623 abstracts, 14 studies were included in the final analysis, 11 of which
are reported here. Two quantitative studies as well as 1 mixed method study on
self-care could not be reported on here due to word limitations. Adult people who
self-harm described the importance of quality in the caring relationship and a
tailored care designed for each individual. There is a need for more studies into
adolescents who self-harm but of importance is the adolescents' need for support
from the adult world. A positive relationship between patient and healthcare
professional can be crucial in motivating continued treatment of people who self
harm. A major priority is radical improvement in the attitudes of healthcare
personnel.
PMID- 28426392
TI - Design and validation of a new method to detect and quantify residual host cell
DNA in human recombinant erythropoietin (rEPO).
AB - During the purification of human recombinant erythropoietin (rEPO) from host
cells, residual DNA may remain in final products. This contamination is a risk
factor for patients and may result in the inactivation of some tumor suppressor
genes or activation of oncogenes if its concentration is more than the standard
defined by WHO. Based on WHO's criteria, acceptable level of residual DNA in
biopharmaceuticals is less than 10-100 pg/dose. In this study, we have designed a
sensitive and specific quantitative real-time polymerase chain reaction (PCR)
assay for the detection of residual DNA in human rEPO products. All reported
sequences of CHO's GAPDH gene were retrieved from GenBank, and a multiple
alignment was performed using Mega 6 software to find conserved regions of the
gene. Primers and probe were designed by AlleleID7 software for the highly
conserved region. Quantitative real-time PCR showed an R2 value more than 0.99
and the efficiency equal to 101% indicating a highly accurate and efficiency of
the reaction, respectively. Based on the standard curve, the limit of detection
of the assay was determined to be 10 copies/uL (0.00967 fg/uL). In addition, the
inter- and intra-assay of the test were determined to be 1.14% and 0.65%,
respectively, which are in acceptable range according to the WHO's guidelines.
PMID- 28426394
TI - Attending the Wake of a Patient With a "Difficult" Family.
PMID- 28426395
TI - Compassion Fatigue and Compassion Satisfaction in Hospice Social Work.
AB - As part of the interprofessional team of hospice caregivers, social workers are
exposed to multiple stressors, both in their work with dying patients and their
families and in functioning as professionals within rapidly changing health care
organizations. Ongoing exposure to such stressors prompts concern about the
emotional and psychological effect working with people who are dying may have on
those who do it. Further, an understanding is needed regarding how hospice social
workers interpret the costs and benefits of their work and how they cope with the
dying and loss that pervade their everyday work lives. This descriptive, cross
sectional study explored the prevalence of compassion fatigue among hospice
social workers and considered compassion satisfaction as a means to mitigate
compassion fatigue. Fifty-five hospice social workers from 34 hospice
organizations in Michigan completed an online survey. Results suggested that
compassion fatigue is indeed a concern among hospice social workers. In addition,
compassion fatigue and compassion satisfaction were found to be negatively
correlated and suggested that compassion satisfaction may act as a protective
mechanism against compassion fatigue. These results may provide insight regarding
how best to mitigate this professional hazard in end-of-life social work.
PMID- 28426396
TI - Current Status of and Recommendations for Nutrition Education in Gastroenterology
Fellowship Training in Canada.
AB - PURPOSE: Knowledge and skill in the area of nutrition are a key competency for
the gastroenterologist. However, standards for nutrition education for
gastroenterology fellows in Canada do not exist, and gastroenterologists in
training and in practice do not feel confident in their knowledge or skill as it
relates to nutrition. This study was undertaken to identify the current status of
nutrition education in gastroenterology (GI) fellowship training programs in
Canada and to provide insight into the development of nutrition educational
goals, processes, and evaluation. METHODS: Using mixed methods, we did a survey
of current and recent graduates and program directors of GI fellowship programs
in Canada. We undertook a focus group with program directors and fellows to
corroborate findings of the survey and to identify strategies to advance
nutrition education, knowledge, and skill of trainees. RESULTS: In total, 89.3%
of the respondents perceived that the nutrition education was important for GI
training, and 82.1% of the respondents perceived nutrition care would be part of
their practice. However, only 50% of respondents had a formal rotation in their
program, and it was mandatory only 36% of the time. Of the respondents, 95% felt
that nutrition education should be standardized within GI fellowship training.
CONCLUSIONS: Significant gaps in nutrition education exist with GI fellowship
programs in Canada. The creation of standards for nutrition education would be
valued by training programs, and such a nutrition curriculum for GI fellowship
training in Canada is proposed.
PMID- 28426397
TI - A Successful Debrief Program for House Staff.
AB - Challenging end-of-life encounters can be stressful and may lead to burnout.
Monthly debriefing sessions are led by a physician and clinical social worker
(LCSW). Sessions focus on experiences and emotional reactions rather than case
details. Themes identified included; feeling unsupported after difficult deaths,
identifying with patients emotionally, and conceptualizing a "good" versus "bad"
death. Debriefing provides opportunities for residency physicians to reflect on
the affective side of their work and helps promote resiliency.
PMID- 28426398
TI - K-RAS and N-RAS mutations in testicular germ cell tumors.
AB - Testicular cancer is a relatively rare tumor type, accounting for approximately
1% of all cancers in men. However, among men aged between 15 and 40 years,
testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell
tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene
controls several cellular functions, including cell proliferation, apoptosis,
migration, and differentiation. Thus, RAS signaling is important for normal germ
cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over
20% of all cancers. RAS gene mutations have also been reported in TGCTs. We
investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT
patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases
were included in the study. K-RAS and N-RAS analyses were performed in our
molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In
total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5
non-seminoma cases (26%) [p = 0.55]. A K-RAS mutation was present in 4 pure
seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS
mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%)
[p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one
with seminoma tumor and the other with non-seminoma tumor. To date, no approved
targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS
and N-RAS mutations in these tumors may provide more treatment options,
especially in platinum-resistant tumors.
PMID- 28426400
TI - Morphological description of Cosmocerca sp. (Nematoda: Cosmocerdidae) from the
Mascarene grass frog Ptychadena cf. mascareniensis (Amphibia: Ptychadenidae). A
light and scanning electron microscopic studies.
AB - The Mascarene grass frog Ptychadena cf. mascareniensis is a species of frog with
a vast area of distribution in Africa. A total of 300 frog specimens were
collected from different localities at El-Giza province, Egypt; then dissected
and examined for the presence of parasitic infection. Only eighty six (28.66%)
specimens were found to be naturally infected with nematode parasite. Seasonally,
the prevalence of infection was reached its maximum value of 74.66% during summer
and minimum values of 26.66% (20/75), 13.33% (10/75) during spring and autumn,
respectively; while no records were observed during winter season. The morphology
of the recovered parasite was studied by using light and scanning electron
microscopy. The adult worm characterized by anterior extremity with small mouth
opening being surrounded by three lips provided with four sub-median cephalic
papillae and one pair of lateral amphids. Body measurements showed that male
worms were smaller than females measuring 1.22-2.43 (2.21 +/- 0.1) mm in length
and 0.21-0.34 (0.29 +/- 0.01) mm in width. Females measured 1.9-3.7 (2.8 +/- 0.1)
mm in length and 0.24-0.42 (0.38 +/- 0.01) mm in width. Comparing the present
parasite with other species of the same genus described previously, several
similarities were observed. However, peculiar new characteristics such as the
arrangement of plectanes and somatic papillae, the presence of gubernaculum, the
position of nerve ring, excretory pore, and vulval opening make it reasonable
belongs to the family Cosmocercidae and identified as Cosmocerca sp. In addition,
the present study was the first report for occurrence of cosmocercid species from
the Mascarene grass frog in Egypt.
PMID- 28426401
TI - A new species of the quill mite genus Chenophila Kethley, 1970 (Acariformes:
Syringophilidae) from the Marbled Teal Marmaronetta angustirostris (Menetries)
(Anseriformes: Anatidae) in Turkey.
AB - A new species of parasitic mite of the family Syringophilidae (Acariformes:
Cheyletoidea), Chenophila marmaronetta sp. nov. is described from the secondary
quill feathers of Marmaronetta angustirostris (Menetries) (Anseriformes:
Anatidae) from Turkey. This species differs from closely related Ch.
platyrhynchos Tymcio et al., 2013 by the presence of 9 chambers in each medial
branch of the peritremes (vs 5 chambers in Ch. platyrhynchos), length of the
stylophore 220-235 (vs 255-275), and lengths of setae vi, ve, d1 and d2 40-55, 65
70, 90-105 and 170, respectively (vs 65-85, 80-100, 130-170 and 85-150).
PMID- 28426402
TI - Molecular identification of Thelandros scleratus and Thelastoma icemi (Nematoda:
Oxyruida) using mitochondrial cox 1 sequences.
AB - Two species of parasitic nematodes collected from the intestine of Brook's House
Gecko, Hemidactylus brooki and American cockroach, Periplaneta americana L. The
parasites were identified as Thelandros scleratus and Thelastoma icemi by PCR
amplification method. Subsequently, sequence analysis of mt cox1 (504 and 540 bp)
for T. scleratus and T. icemi respectively revealed that these sequences showed
maximum similarity of 90% (in case of T. scleratus), 77% (in case of T. icemi),
to nematode sequences available on GenBank. To our knowledge, no cox1 sequence is
available for both the species of family Pharyngodonidae and Thelastomatidae.
This study represents the first mitochondrial DNA characterization of both
species.
PMID- 28426403
TI - PCR denaturing gradient gel electrophoresis as a useful method to identify of
intestinal bacteria flora in Haemaphysalis flava ticks.
AB - Ticks are blood-sucking ectoparasites of great medical and veterinary
significance that can transmit bacteria, protozoa, fungi and viruses, causing a
variety of human and animal diseases worldwide. In the present study, the
intestinal bacterial flora associated with Haemaphysalis flava ticks in different
developmental stages were analyzed using polymerase chain reaction (PCR) and
denaturing gradient gel electrophoresis (DGGE). Eleven distinct DGGE bands were
found using PCR-DGGE method. Sequences analyses indicated that they belonged to
Bacillus cereus, Candidatus rickettsia, Erwinia sp., Klebsiella pneumoniae,
Pectobacterium carotovorum, Pseudomonas aeruginosa, Rickettsia peacockii,
Rickettsia helvetica, Rickettsia slovaca, Staphylococcus simulans and Uncultured
bacterium clone. Our find that the K. pneumoniae and P. aeruginosa isolates were
presented in all H. flava ticks in different developmental stages. The present
results indicated that zoonotic pathogens are present in H. flava ticks in Henan
province, China. To our knowledge, this is the first report on intestinal
bacterial flora associated with H. flava ticks in China.
PMID- 28426404
TI - The ruby-crowned tanager Tachyphonus coronatus Vieillot, 1822 (Passeriformes:
Thraupidae) as a new host for Isospora ramphoceli Berto, Flausino, Luz, Ferreira,
Lopes, 2010 in Brazil.
AB - Despite 12 coccidian species had been recorded from passerines of the Thraupidae
family, none of them has been reported in the Parque Nacional do Itatiaia, in
Southeastern Brazil. This locality is a protected area with a high degree of
vulnerability, and is considered a "conservation island" of biodiversity. The aim
of the current work was describe Isospora ramphoceli Berto, Flausino, Luz,
Ferreira, Lopes, 2010 from ruby-crowned tanagers Tachyphonus coronatus Vieillot,
1822 in the Parque Nacional do Itatiaia. The oocysts of I. ramphoceli are
subspheroidal, 23.1 * 22.1 MUm, with smooth, bilayered wall. Micropyle, oocyst
residuum and polar granule are absent. Sporocysts are ellipsoidal or ovoidal,
16.2 * 10.8 MUm. Stieda body is knob-like and substieda body is large and
homogeneous. Sporocyst residuum is composed of many scattered granules.
Sporozoites are vermiform with a posterior refractile body and a nucleus. In
addition to new locality, this is the first description of I. ramphoceli from T.
coronatus.
PMID- 28426405
TI - Molecular evidence and additional morphological characters to distinguish
Ornithodoros brodyi and Ornithodoros yumatensis (Ixodida: Argasidae) in their
different developmental stages.
AB - Ornithodoros brodyi and Ornithodoros yumatensis are two species distributed in
the Americas and associated with bats and caves. Both species have similar
morphology, and the diagnostic traits of adults have not been detailed or
illustrated accurately. In this study, the independence of both species is
validated on the basis of molecular evidence (using partial sequences of 16S rDNA
gene), and the morphological differences between them (dentition of the hypostome
and traits of individual mammillae) are confirmed through light and scanning
electron microscopy. In addition to the above characteristics, we observed other
traits that may serve to differentiate both species: dorsal setae are short and
thick in O. yumatensis and are thin and moderate in size in O. brodyi. We also
observed a conspicuous hood in O. brodyi, which was absent in O. yumatensis.
Another characteristic observed is a line of setae, near the end of Tarsi II-IV,
which in O. brodyi is formed by less than five setae and in O. yumatensis by more
than five. The main morphological difference between larvae of the 2 species is
the number of ventral setae [9 (4 circumanal pairs) in O. brodyi and 8 (3
circumanal pairs) in O. yumatensis]. The genetic divergence in 16S rDNA sequences
between these two species ranges from 9.7 to 10.6%.
PMID- 28426406
TI - Infection of the lesser spotted dogfish with Proleptus obtusus Dujardin, 1845
(Nematoda: Spirurida) reflects ontogenetic feeding behaviour and seasonal
differences in prey availability.
AB - Proleptus obtusus Dujardin, 1845 is the most common parasite infecting the gut of
the lesser spotted dogfish (Scyliorhinus canicula, Linnaeus). This nematode is
trophically transmitted from an intermediate crustacean host to the definitive
elasmobranch host. Sexual and age-related differences in habitat occupancy and
feeding behaviour of the lesser spotted dogfish make this parasite-host dyad
ideal for testing which aspects of host biology influence parasite transmission.
Here, the relationship between P. obtusus burden and host condition, sex and age
were investigated in lesser spotted dogfish captured in the Northeast Atlantic.
Prevalence of P. obtusus was of 94.8% with a mean abundance of 23.3 worms per
host. Our results indicate that parasite burden is best explained by the
interaction between ontogenetic differences in foraging behaviour of the lesser
spotted dogfish and seasonal differences in prey availability.
PMID- 28426407
TI - Helminth (Cestoda, Nematoda) and coccidian (Apicomplexa: Eimeriidae) parasites of
the eastern small-footed myotis, Myotis leibii (Chiroptera: Vespertilionidae)
from Arkansas, with a description of a new species of Eimeria.
AB - During May and July 2016, 32 eastern small-footed myotis (Myotis leibii) were
collected from five counties of northwestern Arkansas and their faeces examined
for coccidian parasites. Four of 32 (13%) M. leibii harboured an eimerian that we
describe here as new. Oocysts of Eimeria sassei sp. n. were ovoidal to
ellipsoidal with a bi-layered wall and measured (length * width, L * W) 18.3 *
15.2 um, with an L/W ratio of 1.2. A micropyle and oocyst residuum were absent
but 1-2 polar granules were present. Sporocysts were ovoidal, 9.6 * 6.3 um, with
an L/W ratio of 1.5. A pronounced, button-like Stieda body was present but
substieda and parastieda bodies were absent. A sporocyst residuum was present as
distinct aligned or dispersed granules. One bat that we found dead was examined
for helminth parasites. It harbored the tapeworm, Vampirolepis sp. and a
nematode, Seuratum cancellatum. This is the first coccidian as well as the second
helminths reported from M. leibii. In addition, this is the seventh species of
coccidian parasite documented from Arkansas bats.
PMID- 28426408
TI - Isolation and molecular characterization of a Naegleria strain from a
recreational water fountain in Tenerife, Canary Islands, Spain.
AB - Free-Living Amoebae (FLA) are widely distributed protozoa in the environment and
have been isolated from many sources such as dust, soil and water. Among the
pathogenic genera included in this group Acanthamoeba spp., Naegleria fowleri and
Balamuthia mandrillaris have been reported to be causative agents of lethal
encephalitis, disseminated infections and keratitis. Naegleria fowleri is a
pathogenic FLA species which causes Primary Amoebic Meningoencephalitis (PAM). At
present there are not many available data on the distribution of Naegleria
species in Spain from environmental sources. Therefore, the aim of this study was
to evaluate the presence of this genus in recreational water sources in the
island of Tenerife, Canary Islands, Spain. In this study, ten samples collected
from recreational water fountains were checked for the presence of Naegleria spp.
using morphological and molecular identification tools. From the analysed
samples, only one sample (seawater fountain) was positive for Naegleria spp.
interestingly, not many reports of Naegleria spp. in seawater are available in
the literature and thus awareness should be raised among the environmental and
public health professionals.
PMID- 28426409
TI - A new species of Oochoristica (Cyclophyllidea: Linstowiidae) from non-native
Mediterranean geckos, Hemidactylus turcicus (Sauria: Gekkonidae), from Texas,
USA.
AB - A new species of cyclophyllidean tapeworm, Oochoristica harschi sp. nov. is
described from 2 of 18 (11%) non-native Mediterranean geckos (Hemidactylus
turcicus) collected in June 2016 from Tom Green County, Texas, USA The new
species has few characteristics in common with 17 species of Oochoristica
previously described from Nearctic reptiles. Of this group, O. harschi is most
similar to O. macallisteri Bursey and Goldberg, 1996 from the side-blotched
lizard, Uta stansburiana from Arizona and California, USA, in number of testes,
14-20 vs. 12-20. However, O. harschi has oval suckers and a long neck compared to
the circular suckers and absent neck in O. macallisteri. On comparison with other
species of Oochoristica, it was found O. chinensis Jensen, Schmidt and Kuntz,
1983 from the Sino-Japanese realm, O. iguanae Bursey and Goldberg, 1996 from the
Neotropical realm, and O. maccoyi Bursey and Goldberg, 1966 from the Panamanian
realm were most similar to the new species. However, O. harschi can be
differentiated by possessing a much longer neck and a shorter cirrus pouch. It
can be further differentiated from O. chinensis by possessing an ovoid vs. an
irregular vitellarium, from O. iguanae by having a smaller strobilus (65 vs. 110
mm) as well as an ovoid vs. a triangular vitellarium, and from O. maccoyi by
having significantly more proglottids (145 vs. 89) and a longer strobilus (65 vs.
20 mm). The new species is the fifth species of Oochoristica reported from non
native H. turcicus and the 18th species described from the Nearctic region.
PMID- 28426410
TI - Nematode parasites of the Chilean Flamingo, Phoenicopterus chilensis
(Phoenicopteridae) from Central Argentina, with a description of a new species of
Tetrameres (Tetrameridae).
AB - During the summer of 2013, several specimens of Phoenicopterus chilensis
(Phoenicopteridae) were found dead from unknown causes, in lakes from the
endorheic system "Encadenadas del Oeste", Buenos Aires Province, Argentina. Two
species of Nematoda were recovered from the proventriculus, one of them new for
science. The tetramerid Tetrameres (Tetrameres) salina n. sp. is mainly
characterized by having reduced pseudolabia, lips absent, six bifid teeth, males
with lateral alae, four rows of somatic spines and length ratio of spicules 1:12
32, and large females with eggs lacking polar filaments. The acuariid, Echinuria
skrjabinensis is described and illustrated, this finding represent the second
report of this nematode in Argentina and the first record in flamingos. This is
the first record of helminths parasitizing wild Chilean Flamingos, but it is not
possible to ensure that they accomplish their life cycle in this system of lakes,
because the migratory movements of the population of flamingos studied are
unknown.
PMID- 28426411
TI - Toxoplasma gondii in backyard pigs: seroepidemiology and mouse bioassay.
AB - The aim of this study was to evaluate the occurrence of Toxoplasma gondii in
backyard pigs destined for human consumption in Pernambuco state, Brazil. Blood
and tissue samples (liver, heart, brain, lung and diaphragm) were collected from
224 pigs from legal slaughterhouses and tested for T. gondii infection.
Antibodies to T. gondii were found in the sera of 37.9% (85/224) by using the
immunofluorescence antibody test (cut-off - 1:64). Tissue samples from
seropositive pigs were bioassayed in mice. Tissue samples from seropositive pigs
and from mice of the bioassay were submitted to histopathology,
immunohistochemistry, polymerase chain reaction (PCR) and sequencing; 14.1% of
pig tissue samples and 27.7% of bioassayed mouse samples were positive for T.
gondii DNA, but all pig and mouse tissues were negative in histopathology
analysis and immunochemistry. By using a risk assessment questionnaire, there was
significant difference (p<0.001) in seroprevalence of 21.2% (reproducer) and 3.1%
(finishing pig). These data serve as indicative of the sanitary conditions and
risk of T. gondii infection for backyard pigs. Preventive measures must be
implemented by health services to avoid toxoplasmosis human cases due to
ingestion of pig meat.
PMID- 28426412
TI - Fatal aelurostrongylosis in a kitten in Serbia.
AB - This paper describes a case of aelurostrongylosis in a four-month old female
domestic cat (Felis catus) from South Banat, Serbia. The kitten that had died
suddenly without signs of illness was autopsied in the Veterinary Specialised
Institute "Pancevo". The macroscopic finding was typical of granulomatous
pneumonia and subsequently, histopathology revealed verminous pneumonia. Based on
the parasite morphology, it was confirmed that the lung lesions were caused by
Aelurostrongylus abstrusus. The present finding contributes to the knowledge of
the prevalence of this underestimated parasite in the Balkan Peninsula.
PMID- 28426413
TI - New record of Steinernema arenarium (Artyukhovsky) (Rhabditida: Steinernematidae)
from Ukraine and a note on its distribution.
AB - During a survey of the biodiversity of entomopathogenic nematodes in Ukraine, a
population of Steinernema arenarium, strain Ch, was recovered in the sensitive
Chornobyl Exclusion Zone. In the present work, this strain was morphologically
and molecularly characterised using light microscopy and the sequences of the ITS
and D2-D3 region of the 28S rDNA. In addition, we sequenced the ITS and D2-D3
regions of four populations of S. arenarium from a laboratory collection.
Phylogenetic analyses were performed and the phylogenetic structure and
geographic distribution of S. arenarium are discussed.
PMID- 28426414
TI - Amoebicidal activity of alpha-bisabolol, the main sesquiterpene in chamomile
(Matricaria recutita L.) essential oil against the trophozoite stage of
Acanthamoeba castellani Neff.
AB - Acanthamoeba genus includes opportunistic pathogens which are distributed
worldwide and are causative agents of a fatal encephalitis and severe keratitis
in humans and other animals. Until present there are not fully effective
therapeutic agents against this pathogen and thus the need to search for novel
anti-amoebic compounds is urgent. Recently, essential oils of aromatic and
medicinal plants have shown activity against Acanthamoeba strains. Therefore,
this study was aimed to evaluate the activity of main component of chamomile
essential oil (a sesquiterpene) namely alpha-bisabolol against the Acanthamoeba
castellani Neff strain. After evaluation of the activity and toxicity of this
molecule, IC50 values of 20.839 +/- 2.015 for treated amoebae as well as low
citotoxicty levels in a murine macrophage cell line was observed. Moreover, in
order to elucidate mechanism of action of this molecule, changes in chromatin
condensation levels, permeability of the plasmatic membrane, the mitochondrial
membrane potential and the ATP levels in the treated amoebic strains were
checked. The obtained results revealed that alpha-bisabolol was able to induce
apoptosis, increase the permeability of the plasmatic membrane and decrease both
mitochondrial and ATP levels in the treated amoebae. Therefore, and given the
obtained results, alpha-bisabolol could be used a future therapeutic agent
against Acanthamoeba infections.
PMID- 28426415
TI - Detection of Echinococcus multilocularis DNA in fruit, vegetable, and mushroom
samples collected in the non-endemic territory of the Pomerania province and
comparison of the results with data from rural areas of the neighbouring highly
endemic Warmia-Masuria province, Poland.
AB - Echinococcus multilocularis is a tapeworm that may cause alveolar echinococcosis
(AE), one of the most dangerous parasitic zoonoses. As in the case of some
foodborne diseases, unwashed fruits and vegetables contaminated with eggs of E.
multilocularis may serve as an important transmission route for this parasite.
The aim of this study was to investigate the presence of E. multilocularis DNA in
fruit, vegetables, and mushrooms in rural areas of the Pomerania province, Poland
(non-endemic territory). In total, 104 environmental fruit, vegetable, and
mushroom samples collected in forests, plantations, and kitchen gardens were
analysed using nested PCR based on the mitochondrial 12S rRNA gene. E.
multilocularis DNA was detected in 6.7 % of the samples tested, which indicated
that the environment of the Pomerania province is contaminated with this
parasite, creating a potential risk for humans. Therefore, fresh fruit,
vegetables, and mushrooms should be washed before consumption. Additionally, the
results showed that the level of contamination is significantly lower than in the
highly endemic Warmia-Masuria province. The differences in the occurrence of E.
multilocularis in the environment of these neighbouring provinces appears to be
connected with the general epidemiological situation of these two regions, but
further study is required for an exact explanation.
PMID- 28426416
TI - How does host ecology influence sampling effort in parasite diversity estimates?
A case study using Neotropical freshwater fishes.
AB - Accurately estimating biodiversity is fundamental to ecological understanding and
prediction. Helminthes are often neglected in biodiversity estimates and when
included are often underestimated. Here we examine how sampling effort affects
estimates of parasite diversity in an assemblage of freshwater fish from a
floodplain in Brazil. We also examine how ecological and behavioral factors
influence the sampling effort necessary to accurately estimate the parasite
diversity associated with a fish species. We use our dataset to suggest that host
species with wide geographic distribution (i.e., long migrations), gregarious
behavior (i.e., shoal), larger body size, higher population density, wide diet
breadth (i.e., omnivorous), and autochthonous origin, increase the effort
necessary to estimate the total diversity of parasites. However, estimating this
parasitic fauna has several restrictions and limitations, due to the highly
complex of the floodplain ecosystems, with non-linear and non-random responses.
PMID- 28426417
TI - Neuropathological lesions of clinical and sub clinical Coenurosis (Coenurus
cerebralis) in organized goat farms in India.
AB - Clinical and sub clinical cases of Coenurosis due to Coenurus cerebralis in goats
were documented based on clinical, post mortem examination, identification of
parasitic stages, gross and histopathological lesions in brain of animals died
due to abnormal neurological symptoms. The most prominent site of predilection of
coenuri cysts in brain was cerebral hemispheres and multiple cysts were found in
majority of the cases. Generalized congestion, thinning of brain parenchyma due
to pressure atrophy, gliosis, neuronal degeneration, protoscolices in brain
parenchyma and inflammatory cell reactions predominantly comprised of lymphocytes
and macrophages were prominent neuropathological lesions observed in brain. This
study had significant implications in understanding the neuropathological lesions
to suggest suitable prevention and control measures in organized goat farms in
India.
PMID- 28426418
TI - First report on molecular evidence of Tylodelphys cerebralis (Diplostomulum
cerebralis) Chakrabarti, 1968 (Digenea: Diplostomidae) from snakehead fish Channa
punctata.
AB - Freshwater snakehead fish, Channa punctata (Perciformes: Channidae) from Meerut
(U.P.), India were screened for infection with metacercaria from the eye
(vitreous humor) and brain (cranial cavity) and were analyzed by molecular
methods using PCR and sequencing of the complete internal transcribed spacers
(ITS1-5.8S-ITS2) of the ribosomal RNA gene. Recovered metacercariae from sites,
vitreous humor and cranial cavity were previously diagnosed as Diplostomulum
cerebralis Chakrabarti, 1968 on the basis of morphological characteristics. A
combination of molecular methods in this study depicts that this is a species of
genus Tylodelphys Diesing, 1850 which was misinterpreted as Diplostomulum. Hence,
in this study, we validated the status of T. cerebralis (=D. cerebralis) after 49
years from its original description. The present work might contribute to expand
our knowledge for identification, biodiversity and taxonomy of diplostomids in
Indian fishes.
PMID- 28426419
TI - Ecological implications of floods on the parasite communities of two freshwater
catfishes in a Neotropical floodplain.
AB - The parasite communities of two freshwater catfishes (Auchenipterus osteomystax
and Trachelyopterus galeatus) were analyzed during the dry and rainy seasons in a
Neotropical floodplain. The nature of river-floodplain systems places specific
demands on parasite community structure, due to changes in the host environment.
It was therefore hypothesized that flood conditions lead to an increase in the
richness and abundance of fish parasites in the rainy season at the mouth of
Aguapei River floodplain. The Auchenipterus osteomystax parasite community was
richer (11 vs. eight) in species than T. galeatus, although the latter exhibited
a greater parasite burden (F1,108 = 126.99, P<0.0001). During the rainy season
both host species demonstrated high levels of parasitism (least squared means +/-
SE = 1.69 +/- 0.05 vs. 1.34 +/- 0.05; F1,108 = 21.45, P<0.0001). Differences were
found in the composition of the parasite species and the proportion of parasites
for each host species and between each seasonal period. Flood conditions during
the rainy season caused a change in the composition and structure of the
parasitic communities. The results corroborate the hypothesis that floods are one
of the most significant influences on shaping the parasite communities of fish in
floodplains. Our greatest concern is the reduction these dynamics and effects
bring about on local biota and, consequently, in host-parasite interaction. We
would therefore like to take this opportunity to warn environmental agencies and
hydroelectric companies about the importance of the conservation of the diversity
of this location.
PMID- 28426420
TI - Disruption of egg production by triclabendazole-resistant Fasciola hepatica
following treatment with a commercial preparation of myrrh (Mirazid).
AB - An in vitro study has been carried out to monitor changes to the female
reproductive system in adult triclabendazole (TCBZ)-resistant Fasciola hepatica
following treatment with a commercial preparation of myrrh ("Mirazid"). Flukes
were immersed for 6 h and 24 h in myrrh extract at a concentration of 200 ug/ml,
then processed for histological and transmission electron microscope (TEM)
examination of the uterus, Mehlis' gland, ovary and vitellaria. Egg production
had become abnormal at 6 h post-treatment (pt), with the uterine lumen being
filled with free vitelline cells and masses of shell protein material; few eggs
were present. At 24 h pt, no eggs were present. Distinct changes to the ovary and
Mehlis' gland were only observed after 24 h incubation in Mirazid. The ovary
contained numbers of apoptotic oogonia and oocytes. In the Mehlis' gland, the S1
cells were disorganised and the processes from them were vacuolated, although the
disruption was not significant. More severe changes were observed in the
vitelline cells and follicles. After 6 h incubation in Mirazid, although the
gross organisation of the vitelline follicles appeared to be normal, nuclear
changes indicative of the early stages of apoptosis were observed in the stem
cells and shell protein production by the mature cells had decreased. At 24 h pt,
a distinct shift in cell population was evident, with the follicles containing
mainly mature cells and spaces were present between the cells. The shell globule
clusters in the mature cells were disorganised. In more severely-affected
follicles, cells were seen to be breaking down, with karyolytic nuclei and
disintegrating cytoplasm. Overall, the results have shown that exposure to
Mirazid treatment had a severe impact on egg production by TCBZ-resistant flukes,
an effect that was mediated by disruption of the vitelline cells and of the
mechanism co-ordinating egg formation in the ootype.
PMID- 28426421
TI - Redescription of Philometra margolisi Moravec, Vidal-Martinez et Aguirre-Macedo,
1995 (Nematoda: Philometridae), a gonad-infecting parasite of the red grouper
Epinephelus morio (Serranidae) in the Gulf of Mexico.
AB - The insufficiently known nematode species Philometra margolisi Moravec, Vidal
Martinez et Aguirre-Macedo, 1995 (Philometridae) is redescribed based on light
and scanning electron microscopical (SEM) examinations of specimens collected
from the gonad of the type host, the red grouper Epinephelus morio (Valenciennes)
(Serranidae, Perciformes), in the northern Gulf of Mexico off Florida, USA. Also,
new prevalence data for females of P. margolisi were derived from 188 fish, and a
subset of these (n = 38) were used to determine prevalence and intensity of male
nematodes. The male of this species was studied with SEM for the first time,
which revealed some new, taxonomically important morphological features. The male
posterior end had a V-shaped caudal mound, four pairs of minute adanal papillae,
a pair of large papillae located posterior to the cloacal aperture and a pair of
very small phasmids. The distal end of the gubernaculum is unique among all gonad
infecting species of Philometra parasitizing serranids in that its ventral
surface is flat, smooth, without the usual two longitudinal grooves; the dorsal
lamellate structures on the gubernaculum are also different in this species. In
contrast to data in the original species description, the body length of gravid
females of P. margolisi was 132-280 mm. Overall prevalence for male nematodes
(76.3%) was much higher than for females (15.4%), and female nematode prevalence
was higher in samples collected during host spawing season than out of season
(27.1% and 3.3%, respectively).
PMID- 28426422
TI - Morphological re-description of Electrotaenia malapteruri (Cestoda:
Proteocephalidae) and Dujardinnascaris malapteruri (Nematoda: Heterocheilidae)
infecting the Electric catfish Malapterurus electricus and heavy metal
accumulation in host and parasites in relation to water and sediment analysis in
Lake Manzala, North Delta, Egypt.
AB - Parasites are one of the most serious limiting factors in aquaculture. The
Electric catfish Malapterurus electricus was subjected to study the prevalence
and mean intensity of parasitic infections throughout the whole year of 2015.
Heavy metals accumulation in host fish and parasites were determined in relation
to water quality and sediments of two different sites of Lake Manzala (Manzala
and Bahr El-Baqar), Egypt. A total of 100 specimens of Electric catfish were
collected and examined for the presence of helminth parasites. Two parasite
species were recovered and morphologically identified. These were cestoda
Electrotaenia malapteruri and nematode Dujardinnascaris malapteruri. Heavy metal
analysis in water and sediments showed that measured heavy metals in Bahr El
Baqar were found in risky levels higher than permissible limits and Manzala site.
Sediments were found to contain a higher level of metals than water samples.
Heavy metals accumulation in recovered parasites and their host were also
determined and showed significantly higher concentrations in parasites compared
to their host tissues. According to bioconcentration factors, E. malapteruri
showed that highest accumulation rate for all recorded elements up to 302.
Essential elements like Cu and Fe were found in significantly higher
concentrations in D. malapteruri, whereas E. malapteruri accumulated elements Cd,
Pb, Ni, Mn, Zn and Ca to a significantly higher degree. Accordingly, the ratios
(C[D.malapteruri]/C[E. malapteruri]) for most essential elements were higher than
0.5. Therefore, fish cestodes can be regarded as useful bio-indicators more than
nematodes when evaluating the environmental pollution of aquatic ecosystems by
heavy metals.
PMID- 28426423
TI - The discovery of acanthocephalans parasitizing chaetognaths.
AB - A comprehensive literature review shows that 12 types of pathogens,
micropredators and parasites are reported to interact with chaetognaths, mostly
digenean trematodes, cestodes and nematodes larval stages. Through analysis of
78,152 chaetognaths from a monthly zooplankton time series (Jan 1996-Dec 1998)
collected in the Mexican Central Pacific twelve acanthocephalan larvae
parasitizing chaetognaths were discovered. This is the first record of an
acanthocephalan parasitizing chaetognaths, raising to 13 the types of symbionts
known to interact with them (excluding predators). Cystacanth larval specimens of
Corynosoma sp. (Polymorphidae) were observed parasitizing the head, trunk and
caudal cavities of three of the eight chaetognath species inhabiting this
tropical coastal region (Flaccisagitta enflata, Flaccisagitta hexaptera and
Zonosagitta bedoti). Because Corynosoma sp. parasitized chaetognaths during
different months and years (Jan-Feb 1996, Mar and Jul 1997, Jan, Jun, Aug-Sep
1998) and because the total length of these cystacanths varied between 165-480
um, suggesting growth inside the hosts, we conclude that chaetognaths are
intermediate hosts of Corynosoma sp. The twelve parasitized chaetognaths were
juveniles (without gonads) or immature adults (none in reproductively mature
stage IV); therefore Corynosoma may have a negative influence on host
reproduction. Marine crustaceans (amphipods, decapods, copepods, mysids and
euphausiids) and fishes are common intermediate or paratenic hosts of
acanthocephalans. Fish, sea birds and marine mammals are definitive hosts for
marine Corynosoma species. The present discovery implies that acanthocephalans
are transmitted trophically through different intermediate hosts (crustaceans,
chaetognaths and/or fish); thus chaetognaths can also be part of the marine
acanthocephalan life cycle.
PMID- 28426424
TI - cDNA library construction of two human Demodexspecies.
AB - The research of Demodex, a type of pathogen causing various dermatoses in animals
and human beings, is lacking at RNA level. This study aims at extracting RNA and
constructing cDNA library for Demodex. First, P. cuniculiand D. farinaewere mixed
to establish homogenization method for RNA extraction. Second, D. folliculorumand
D. breviswere collected and preserved in Trizol, which were mixed with D.
farinaerespectively to extract RNA. Finally, cDNA library was constructed and its
quality was assessed. The results indicated that for D. folliculorum& D. farinae,
the recombination rate of cDNA library was 90.67% and the library titer was 7.50
* 104 pfu/ml. 17 of the 59 positive clones were predicted to be of D.
folliculorum; For D. brevis& D. farinae, the recombination rate was 90.96% and
the library titer was 7.85 x104 pfu/ml. 40 of the 59 positive clones were
predicted to be of D. brevis. Further detection by specific primers demonstrated
that mtDNA cox1, cox3and ATP6 detected from cDNA libraries had 96.52%-99.73%
identities with the corresponding sequences in GenBank. In conclusion, the cDNA
libraries constructed for Demodexmixed with D. farinaewere successful and could
satisfy the requirements for functional genes detection.
PMID- 28426425
TI - The role of domestic dogs in the transmission of zoonotic helminthes in a rural
area of Mekong river basin.
AB - Dogs have been bred since ancient times for companionship, hunting, protection,
shepherding and other human activities. Some canine helminth parasites can cause
significant clinical diseases in humans as Opisthorchis viverrini causing
cholangiocarcinoma in Southeast Asian Countries. In this study, socio-cultural
questionnaire, canine parasitological analysis, necropsy, parasite molecular
confirmation and dog roaming data were evaluated in Savannakhet, Lao-PDR, a
typical Mekong Basin area. Dog owners comprised 48.8% of the studied population,
with 61.2% owning one dog, 25.1% 2 dogs, 8.5% 3 dogs and 1.8% owning more than 4
dogs. Data from GPS logger attached to dogs showed they walked from 1.4 to 13.3
km per day, covering an area of 3356.38m2 average, with a routine of accessing
water sources. Thirteen zoonotic helminth species were observed. Causative agents
of visceral and cutaneous larva migrans occurred in 44.1% and 70% of the samples
respectively. Spirometra erinaceieuropaei was detected in 44.1% of samples.
Importantly, O. viverrini was found in 8.8% of samples. Besides the known
importance of dogs in the transmission of Ancylostoma spp., Toxocara spp. and S.
erinaceieuropaei, the observed roaming pattern of dogs confirmed it as an
important host perpetuating O. viverrini in endemic areas; their routine access
to waterbodies may spread O. viverrini eggs in a favorable environment for the
fluke development, facilitating the infection of fishes, and consequently
infecting humans living in the same ecosystem. Therefore, parasitic NTDs control
programs in humans should be done in parallel with parasite control in animals,
especially dogs, in the Mekong River basin area.
PMID- 28426427
TI - Three new species of Pharygodonidae (Nematoda: Oxyuridea) in Laudakia tuberculata
(Squamata: Agamidae) from Dehradun, Uttarakhand, India.
AB - Parapharyngodon tuberculata sp. nov., Thelandros tuberculata sp. nov. and
Thelandros dehradunensis sp. nov. (Nematoda: Pharyngodonidae) from the large
intestine of a rock lizard, Laudakia tuberculata Gray, 1827), are described and
illustrated. Parapharyngodon tuberculata sp. nov. is the 8th Oriental species and
59th species assigned to the genus Parapharyngodon and differs from other species
of the genus by possessing 3 pairs of caudal papillae, an echinate cloacal lip,
112-115 um spicule length and postbulbar ovary. Thelandros tuberculata sp. nov.
is the 5th and Thelandros dehradunensis sp. nov. the 6th Oriental species,
respectively, and they are the 40th and 41st species assigned to the genus
Thelandros. They differ from other species of the genus in caudal papillae
arrangement, length of spicules, and structure of the anterior end of the
esophagus. We transfer Parapharyngodon arequipensis Calisaya and Cordova, 1997 to
Thelandros arequipensis (Calisaya and Cordova, 1997) comb. n. based upon the
presence of a terminal operculum in the egg and large, pendant, caudal papillae.
PMID- 28426426
TI - Pseudopecoelus mccauleyi n. sp. and Podocotyle sp. (Digenea: Opecoelidae) from
the deep waters off Oregon and British Columbia with an updated key to the
species of Pseudopecoelus von Wicklen, 1946 and checklist of parasites from
Lycodes cortezianus (Perciformes: Zoarcidae).
AB - Pseudopecoelus mccauleyi n. sp. (Opecoelidae: Opecoelinae) is described from the
intestine of the bigfin eelpout, Lycodes cortezianus (Gilbert, 1890)
(Perciformes: Zoarcidae), collected at 200-800 m depths in the Northeastern
Pacific Ocean off Oregon and Vancouver Island, British Columbia. The new species
is distinguished by possessing a unique combination of the following diagnostic
characters: vitelline fields that extend to the posterior margin of the ventral
sucker; a slender, tubular and sinuous seminal vesicle that extends some distance
into the hindbody; an unspecialized, protuberant ventral sucker; a genital pore
at pharynx level; lobed to deeply multilobed testes; a lobed ovary; and an egg
size of 68-80 MUm * 30-46 MUm. A single specimen of Podocotyle Dujardin, 1845
(Digenea: Plagioporinae) is also described from the intestine of an individual
Coryphaenoides sp. (Gadiformes: Macrouridae) collected at 2,800 m depth off
Oregon. A listing of parasites from the bigfin eelpout as well as observations of
parasite diversity within relevant hosts are offered, new host and locality
records are noted, and a brief discussion of Pseudopecoelus von Wicklen, 1946 in
the deep sea is presented taking note of the low level of host specificity
recorded (i.e. spp. of Pseudopecoelus are now known to parasitize deep-water fish
from at least 20 piscine families). A new dichotomous key to the 39 recognized
species of Pseudopecoelus is introduced.
PMID- 28426428
TI - Vascular calcification: the role of microRNAs.
AB - Vascular calcification represents the deposition of calcium phosphate salts in
the tunica media of the vascular wall. It occurs during aging but is accelerated
and pronounced in patients with diabetes mellitus, chronic kidney disease (CKD)
and established cardiovascular disease. Due to the loss of elasticity of the
vessel wall, vascular calcification might result in left ventricular hypertrophy
and compromise coronary perfusion. Accordingly, several studies showed that
vascular calcification is associated with increased risk for cardiovascular
morbidity and mortality. Accumulating data suggest that microRNAs (miRs) play an
important role in vascular calcification. A variety of miRs have been implicated
in the development of vascular calcification, whereas others appear to play a
protective role. Accordingly, miRs might represent promising targets for the
prevention of vascular calcification and its adverse cardiovascular sequelae.
However, given the complexity of regulation of this process and the multitude of
miRs involved, more research is needed to identify the optimal candidate miRs for
targeting.
PMID- 28426429
TI - A candidate liquid chromatography mass spectrometry reference method for the
quantification of the cardiac marker 1-32 B-type natriuretic peptide.
AB - BACKGROUND: B-type natriuretic peptide (BNP) is a 32 amino acid cardiac hormone
routinely measured by immunoassays to diagnose heart failure. While it is
reported that immunoassay results can vary up to 45%, no attempt of
standardization and/or harmonization through the development of certified
reference materials (CRMs) or reference measurement procedures (RMPs) has yet
been carried out. METHODS: B-type natriuretic peptide primary calibrator was
quantified traceably to the International System of Units (SI) by both amino acid
analysis and tryptic digestion. A method for the stabilization of BNP in plasma
followed by protein precipitation, solid phase extraction (SPE) and liquid
chromatography (LC) mass spectrometry (MS) was then developed and validated for
the quantification of BNP at clinically relevant concentrations (15-150 fmol/g).
RESULTS: The candidate reference method was applied to the quantification of BNP
in a number of samples from the UK NEQAS Cardiac Markers Scheme to demonstrate
its applicability to generate reference values and to preliminary evaluate the
commutability of a potential CRM. The results from the reference method were
consistently lower than the immunoassay results and discrepancy between the
immunoassays was observed confirming previous data. CONCLUSIONS: The application
of the liquid chromatography-mass spectrometry (LC-MS) method to the UK NEQAS
samples and the correlation of the results with the immunoassay results shows the
potential of the method to support external quality assessment schemes, to
improve understanding of the bias of the assays and to establish RMPs for BNP
measurements. Furthermore, the method has the potential to be multiplexed for
monitoring circulating truncated forms of BNP.
PMID- 28426430
TI - Great need for changes in higher education in Greece.
PMID- 28426431
TI - Automated detection of unstable hemoglobin variants by Sysmex XE-Series
analyzers.
PMID- 28426432
TI - Surface as a motion surrogate for gated re-scanned pencil beam proton therapy.
AB - This simulation study investigated the dosimetric effectiveness and treatment
efficiency of surface motion guided gating of pencil beam scanning (PBS) proton
therapy for liver tumour treatments. Dedicated 4D dose calculations were
performed for simulating gated treatments using 4DCT data for six patients
derived from 4DMRI (4DCT(MRI)). Surface motion as a surrogate for tumour motion
was extracted from the 4DMRI images and a linear internal-external correlation
model applied to derive amplitude-based gating windows (GWs) of 10 and 5 mm. 4D
treatments were simulated using gating and layered/volumetric rescanning (either
alone or combined) and four assumed system latencies (50/100/200/500 ms) for the
response time of the beam gating to the surrogate. Resulting 4D plans were
compared using D5-D95 and V95 in the CTV as the primary metrics, as well as dose
to the healthy liver and total treatment time. With no motion mitigation,
interplay effects deteriorate the dose homogeneity by more than 30% with respect
to the static reference plan, whereas with surface motion guided gating alone,
this could be reduced to 12/20% and 5/10% (mean/max over all cases) for 10 mm and
5 mm GWs, respectively. Furthermore, by combining *5 layered rescans with 5 mm
GW, plan homogeneities to within 1/5% of the static references could be achieved.
Dose inhomogeneities were however still pronounced for latencies ?200 ms but
limited when ?100 ms. ITV volumes could be decreased by 19/25% when 10/5 mm GW
was employed, leading to reductions in mean dose to the healthy liver tissue of
2.6/3.3%. Our results confirm the potential of combining gating and re-scanning
(re-gating) for mitigating large tumor motions, and the potential of surface
motion monitoring as a gating signal.
PMID- 28426433
TI - Specific heat and Hall effect of the ferromagnetic Kondo lattice UCu0.9Sb2.
AB - We have investigated the electrical resistivity rho, specific heat C p and Hall
coefficient R H on a single crystal of a ferromagnetic Kondo lattice UCu0.9Sb2.
The experimental [Formula: see text], C p (T) and [Formula: see text] data
evidence a bulk magnetic phase transition at [Formula: see text] K, and
additionally exhibit an unexpected bump located in the temperature range T C/10-T
C/3. UCu0.9Sb2 has an enhanced electronic specific heat coefficient [Formula: see
text] mJ molK-2, corresponding to Kondo temperature [Formula: see text] K. An
analysis of the Hall effect data for j//(a, b)-plane and H// c-axis reveals that
the low-temperature ordinary Hall coefficient R 0 is positive, suggesting that p
type electrical conductivity is dominant. The density of the carriers at 2 K is
about 0.6 holes f.u.-1, which may categorize the studied compound into class of
low carrier density compounds. Combined gamma and R 0 data divulge an effective
mass of charge carriers [Formula: see text] 27 m e . This finding together with
quite low Hall mobility [Formula: see text] cm2 Vs-1 and Kadowaki-Woods ratio
[Formula: see text] [Formula: see text] cm (mol K2 mJ-1)2, manifest the
development of heavy-fermion state in the ferromagnetic UCu0.9Sb2 compound at low
temperatures.
PMID- 28426434
TI - Neutron scattering by Dirac multipoles.
AB - Scattering by magnetic charge formed by Dirac multipoles that are magnetic and
polar is examined in the context of materials with properties that challenge
conventional concepts. An order parameter composed of Dirac quadrupoles has been
revealed in the pseudo-gap phase of ceramic, high-T c superconductors on the
basis of Kerr effect and magnetic neutron Bragg diffraction measurements.
Construction of Dirac quadrupoles that emerge from centrosymmetric sites used by
Cu ions in the ceramic superconductor Hg1201 is illustrated, together with
selection rules for excitations that will feature in neutron inelastic
scattering, and RIXS experiments. We report magnetic scattering amplitudes for
diffraction by polar multipoles that have universal value, because they are not
specific to ceramic superconductors. To illustrate this attribute, we consider
neutron Bragg diffraction from a magnetically ordered iridate (Sr2IrO4) and
discuss shortcomings in published interpretations of diffraction data.
PMID- 28426435
TI - Surface plasmon resonance in gold nanoparticles: a review.
AB - In the last two decades, plasmon resonance in gold nanoparticles (Au NPs) has
been the subject of intense research efforts. Plasmon physics is intriguing and
its precise modelling proved to be challenging. In fact, plasmons are highly
responsive to a multitude of factors, either intrinsic to the Au NPs or from the
environment, and recently the need emerged for the correction of standard
electromagnetic approaches with quantum effects. Applications related to plasmon
absorption and scattering in Au NPs are impressively numerous, ranging from
sensing to photothermal effects to cell imaging. Also, plasmon-enhanced phenomena
are highly interesting for multiple purposes, including, for instance, Raman
spectroscopy of nearby analytes, catalysis, or sunlight energy conversion. In
addition, plasmon excitation is involved in a series of advanced physical
processes such as non-linear optics, optical trapping, magneto-plasmonics, and
optical activity. Here, we provide the general overview of the field and the
background for appropriate modelling of the physical phenomena. Then, we report
on the current state of the art and most recent applications of plasmon resonance
in Au NPs.
PMID- 28426436
TI - Challenges in computational evaluation of redox and magnetic properties of Fe
based sulfate cathode materials of Li- and Na-ion batteries.
AB - Several Fe-based sulfates have been proposed recently as cathode materials
characterized by a high average operating voltage (i.e. Li2Fe(SO4)2 and
Na2Fe2(SO4)3) or low fabrication temperature (e.g. Na2Fe(SO4)2.2H2O)). In this
work, we apply three methods to evaluate the redox potentials and magnetic
properties of these materials: (1) local density functional theory (DFT) in
Perdew-Burke-Ernzerhof parametrization; (2) rotationally invariant DFT + U; and
(3) DFT + U with magnetic exchange, suggested herein. The U parameters used for
DFT + U calculations have been evaluated by using a linear response method
(this applies to DFT + U as well as DFT + U calculations with a magnetic
exchange term). Moreover, we have performed adjustments of U and, for the case of
magnetic exchange, J parameters, to find better agreement with experimental
measurements of redox and magnetic properties. We find that a self-consistent DFT
+ U/linear response approach yields quite overestimated redox potentials as
compared to experiment. On the other hand, we also show that DFT + U
calculations are not capable of providing a reasonably accurate description of
both redox and magnetic properties for the case of Li2Fe(SO4)2, even when
adjusted U parameters are employed. As a solution, we demonstrate that a DFT +
U methodology augmented by a magnetic exchange term potentially provides more
precise values for both the redox potentials and the magnetic moments of the Fe
ions in the studied materials. Thus our work shows that for a more accurate
description of redox and magnetic properties, further extensions of the DFT + U
method, such as inclusion of the contribution of magnetic exchange, should be
considered.
PMID- 28426438
TI - Perceptions and Attitudes of Romanian People Toward Autopsy Procedures According
to the Level of Knowledge.
AB - In the last decade, Romanian hospitals have been facing a decline in autopsy
rates. This has had a negative impact on medical education and the training of
young doctors. Quite a number of caregivers strongly oppose the carrying out of
autopsies on their deceased loved ones who have died in hospital. Hence, this
study was designed to evaluate how autopsies are perceived by an average person
and whether improved knowledge about autopsies would help reduce people's
reluctance toward them. The study involved 216 willing participants who had
either never had a loved one die in hospital or had never had the power to make a
decision about their dead loved ones' body. The method of data collection used
was a medical inquiry-based questionnaire. Two questionnaires were used, one
before and one after brief information regarding autopsy procedures. Only a small
percentage of subjects really knew the meaning of an autopsy. Initially, they
accepted that it was easier to consent to their own autopsy than to the autopsy
of a loved one. This difference in opinion reduced after they were informed about
autopsies. As for arguments against autopsies, the most frequent were integrity
of the body and religious reasons. It is extremely useful to ensure people have
proper information, in order to help them understand and appreciate the benefits
of postmortem examinations. Religious, social, and cultural arguments might be
put aside if proper information and new educational programs are put in place.
PMID- 28426437
TI - Supersonic transient magnetic resonance elastography for quantitative assessment
of tissue elasticity.
AB - Non-invasive, quantitative methods to assess the properties of biological tissues
are needed for many therapeutic and tissue engineering applications. Magnetic
resonance elastography (MRE) has historically relied on external vibration to
generate periodic shear waves. In order to focally assess a biomaterial or to
monitor the response to ablative therapy, the interrogation of a specific region
of interest by a focused beam is desirable and transient MRE (t-MRE) techniques
have previously been developed to accomplish this goal. Also, strategies
employing a series of discrete ultrasound pulses directed to increasing depths
along a single line-of-sight have been designed to generate a quasi-planar shear
wave. Such 'supersonic' excitations have been applied for ultrasound elasticity
measurements. The resulting shear wave is higher in amplitude than that generated
from a single excitation and the properties of the media are simply visualized
and quantified due to the quasi-planar wave geometry and the opportunity to
generate the wave at the site of interest. Here for the first time, we extend the
application of supersonic methods by developing a protocol for supersonic
transient magnetic resonance elastography (sst-MRE) using an MR-guided focused
ultrasound system capable of therapeutic ablation. We apply the new protocol to
quantify tissue elasticity in vitro using biologically-relevant inclusions and
tissue-mimicking phantoms, compare the results with elasticity maps acquired with
ultrasound shear wave elasticity imaging (US-SWEI), and validate both methods
with mechanical testing. We found that a modified time-of-flight (TOF) method
efficiently quantified shear modulus from sst-MRE data, and both the TOF and
local inversion methods result in similar maps based on US-SWEI. With a three
pulse excitation, the proposed sst-MRE protocol was capable of visualizing quasi
planar shear waves propagating away from the excitation location and detecting
differences in shear modulus of 1 kPa. The techniques demonstrated here have
potential application in real-time in vivo lesion detection and monitoring, with
particular significance for image-guided interventions.
PMID- 28426439
TI - High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare
System.
AB - OBJECTIVES: Elevated mortality has been observed among individuals with opioid
use disorder (OUD) treated in addiction specialty clinics or programs.
Information about OUD patients in general healthcare settings is needed in light
of the current effort to integrate addiction services into primary healthcare
systems. This study examined mortality rates, causes of death, and associated
risk factors among patients with OUD in a large general healthcare system.
METHODS: Mortality data were linked with electronic health records of 2576 OUD
patients cared for in a large university health system from 2006 to 2014.
RESULTS: There were 465 deaths confirmed (18.1% of the study participants),
corresponding to a crude mortality rate of 48.6 per 1000 person-years and
standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4-11.3).
Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer
(16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV])
were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62-2.46)
and alcohol use disorder (HR 1.27, 95% CI 1.05-1.55) were 2 clinically important
indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR]
2.58, 95% CI 1.60-4.17) was associated with increased risk of cardiovascular
death, HCV infection (AHR 2.55, 95% CI 1.52-4.26) with cancer mortality risk, and
HCV (AHR 1.92, 95% CI 1.03-3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95
10.05) with liver-related mortality risk. CONCLUSIONS: Patients with OUD in a
general healthcare system demonstrated alarmingly high morbidity and mortality,
which challenges healthcare systems to find innovative ways to identify and treat
patients with substance use disorder.
PMID- 28426441
TI - Diagnosis of corneal limbal stem cell deficiency.
AB - PURPOSE OF REVIEW: A state of limbal stem cell deficiency (LSCD) can be secondary
to a number of etiologies, resulting in either a reduction in the total number of
limbal stem cells or an abnormality in stem cell function. Initially, the
epithelium becomes irregular and hazy; however, this condition may progress to
persistent corneal epithelial defects, stromal scarring, ulceration, and even
perforation. Since LSCD secondary to a variety of etiologies may be reversible,
and various factors are prognostic of disease progression, timely diagnosis is
important. This review will describe current knowledge of diagnostic techniques
for LSCD and understanding of epithelial stem cell function. RECENT FINDINGS:
Conjunctivalization, regarded as the most reliable clinical finding
diagnostically, can be identified as late staining of epithelium with
fluorescein. While identifying loss of the palisades of Vogt by slit-lamp
examination, can provide a high suspicion of LSCD, but this is not diagnostic.
Impression cytology is a simple, noninvasive technique that aids in the diagnosis
of LSCD, but a negative result also cannot rule out the diagnosis. Recent
findings have also shown that imaging techniques including in-vivo confocal
microscope and optical coherent tomography can also aid in diagnosing LSCD;
however, several challenges remain before these techniques become standard
diagnostic methods in clinical practice. Meanwhile, determination of the absence
of limbal epithelial crypts and focal stromal projections using image
reconstruction techniques may assist in the diagnosis of LSCD. Furthermore,
histologic markers may help not only to improve sensitivity and specificity of
conventional techniques in diagnosis of LSCD, but also to identify human limbal
stem cells and determine their number and function in LSCD. SUMMARY: Efforts to
develop and improve techniques for diagnosing LSCD are ongoing. Increased
knowledge of limbal stem cells and components of their niches may not only help
in understanding the pathogenesis of LSCD but may improve its diagnosis, thereby
ameliorating the prognosis of patients with this devastating disease.
PMID- 28426440
TI - The Impact of Couple HIV Testing and Counseling on Consistent Condom Use Among
Pregnant Women and Their Male Partners: An Observational Study.
AB - BACKGROUND: In sub-Saharan Africa couple HIV testing and counseling (CHTC) has
been associated with substantial increases in safe sex, especially when at least
one partner is HIV infected. However, this relationship has not been
characterized in an Option B+ context. SETTING: The study was conducted at the
antenatal clinic at Bwaila District Hospital in Lilongwe, Malawi in 2016 under an
Option B+ program. METHODS: Ninety heterosexual couples with an HIV-infected
pregnant woman (female-positive couples) and 47 couples with an HIV-uninfected
pregnant woman (female-negative couples) were enrolled in an observational study.
Each couple member was assessed immediately before and 1 month after CHTC for
safe sex (abstinence or consistent condom use in the last month). Generalized
estimating equations were used to model change in safe sex before and after CHTC
and to compare safe sex between female-positive and female-negative couples.
RESULTS: Mean age was 26 years among women and 32 years among men. Before CHTC,
safe sex was comparable among female-positive couples (8%) and female-negative
couples (2%) [risk ratio (RR): 3.7, 95% confidence interval (CI): 0.5 to 29.8].
One month after CHTC, safe sex was higher among female-positive couples (75%)
than among female-negative couples (3%) (RR: 30.0, 95% CI: 4.3 to 207.7). Safe
sex increased substantially after CTHC for female-positive couples (RR 9.6, 95%
CI: 4.6 to 20.0), but not for female-negative couples (RR: 1.2, 95% CI: 0.1 to
18.7). CONCLUSIONS: Engaging pregnant couples in CHTC can have prevention
benefits for couples with an HIV-infected pregnant woman, but additional
prevention approaches may be needed for couples with an HIV-uninfected pregnant
woman.
PMID- 28426442
TI - Amniotic membrane use for management of corneal limbal stem cell deficiency.
AB - PURPOSE OF REVIEW: The current article reviews the most recent surgical
techniques for management of corneal limbal stem cell deficiency (LSCD) using
amniotic membrane tissue. RECENT FINDINGS: Early successes with amniotic membrane
transplantation (AMT) for the treatment of ocular surface disorders have
encouraged clinicians to investigate new applications. The use of AMT as a
temporary patch in emergency cases in which LSCD may develop has considerably
improved the prognosis of these patients. Amniotic membrane does not have stem
cells of its own, but it supports regeneration of limbal epithelial stem cells
(LESCs). Similarly, the combination of AMT with classic surgical techniques has
enhanced the surgical success rates in most case series. Furthermore, based on
its advantageous properties as a cell carrier, new applications to support in
vivo and ex-vivo cell expansion have been reported recently. SUMMARY: LSCD
constitutes a general indication for AMT. Based on the clinical scenario, AMT may
be performed alone to support regeneration of LESCs, in combination with other
surgical techniques, or even supporting the in-vivo or ex-vivo expansion of
LESCs.
PMID- 28426443
TI - Independency of the cardio-ankle vascular index from blood pressure at the time
of measurement.
PMID- 28426444
TI - Fracture Liaison Services.
AB - PURPOSE OF REVIEW: The purpose of this review is to report the evidence of
beneficial effects of Fracture Liaison Service (FLS) including data regarding
their impact on subsequent fracture, mortality risk and cost-effectiveness. This
review also discusses the limitations of these data and the challenges faced
during the implementation of FLS. RECENT FINDINGS: Recent studies showed the
beneficial impact of implementation of FLS on the prevention of subsequent
fracture risk, reduced mortality and cost-effectiveness. However, heterogeneity
of FLS models and small number of studies limited the conclusion about the impact
of FLS on secondary fracture prevention. SUMMARY: Patients with osteoporosis
related fractures are at higher risk of subsequent refractures. These subsequent
fractures are associated with increased morbidity and premature mortality.
However, there is a gap between evidence-based recommendations for postfracture
care and actual clinical practice. FLS care is recommended for the management of
the prevention of secondary fracture. FLS implementation reduces the risk of
subsequent fracture, but the level of evidence is low as the interpretation of
data is limited by the number of studies and their heterogeneity. FLS care
significantly reduces the postfracture mortality, especially in patients with hip
fractures. FLS implementation is cost-effective compared with usual care.
Additional studies (with large sample and long-term follow-up) are needed to
assess the impact of FLS care on subsequent fracture risk.
PMID- 28426445
TI - Small, dense LDL: an update.
AB - PURPOSE OF REVIEW: In this review, we summarize the latest findings on small,
dense LDL (sdLDL) atherogenic particles, including their associations with other
biomarkers. RECENT FINDINGS: Increased sdLDL levels have been reported not only
in different metabolic disorders such as diabetes, obesity and metabolic
syndrome, but also in patients with rheumatoid and psoriatic arthritis as well as
hypothyroidism. A wide range of lipid-lowering, as well as other drug classes,
including novel antidiabetic agents and nutraceuticals, exert favourable effects
on these atherogenic particles. The 'gold standard' methodology for the
assessment of sdLDL has not been established yet. However, the association
between sdLDL and several biomarkers could facilitate their assessment. SUMMARY:
Estimation of sdLDL in daily clinical practice may help with the identification
of patients at high cardiovascular risk and further contribute in directing
specific interventions to prevent and/or decrease such risk.
PMID- 28426446
TI - Providing anesthesia in resource-limited settings.
AB - PURPOSE OF REVIEW: The article reviews the reality of anesthetic resource
constraints in low and middle-income countries (LMICs). Understanding these
limitations is important to volunteers from high-income countries who desire to
teach or safely provide anesthesia services in these countries. RECENT FINDINGS:
Recently published information on the state of anesthetic resources in LMICs is
helping to guide humanitarian outreach efforts from high-income countries. The
importance of using context-appropriate anesthesia standards and equipment is now
emphasized. Global health experts are encouraging equal partnerships between
anesthesia health care providers working together from different countries. The
key roles that ketamine and regional anesthesia play in providing well tolerated
anesthesia for cesarean sections and other common procedures is increasingly
recognized. SUMMARY: Anesthesia can be safely given in LMICs with basic supplies
and equipment, if the anesthesia provider is trained and vigilant. Neuraxial and
regional anesthesia and the use of ketamine as a general anesthetic appear to be
the safest alternatives in low-resource countries. Environmentally appropriate
equipment should be encouraged and pulse oximeters should be in every
anesthetizing location. LMICs will continue to need support from outside sources
until capacity building has made more progress.
PMID- 28426447
TI - Measles Cases in Children Requiring Hospital Access in an Academic Pediatric
Hospital in Italy, 2008-2013.
AB - BACKGROUND: The Lazio region is one of the Italian regions where sustained
measles transmission continues to occur. We investigated measles cases reported
by the emergency department (ED) of the largest pediatric hospital in Italy,
located in Lazio. METHODS: We reviewed clinical records of all measles cases from
0 to 18 years of age evaluated in the ED in 2008-2013. We compared demographic
and clinical characteristics of patients admitted to the inpatient setting with
those of patients discharged home to assess possible determinants of hospital
admission. RESULTS: Of 248 patients with measles evaluated in the ED, 113 (45.6%)
were admitted as inpatients. The number of measles cases peaked in 2011 (N = 122;
49.2%), when epidemics were reported in Lazio. Median age was 2.7 years (range:
21 days to 17.9 years), and 31 patients (13%) had an underlying chronic illness.
The strongest independent predictor of hospitalization was having an underlying
chronic illness [adjusted odd ratio (OR): 9.87; 95% confidence interval: 3.13
31.13]. Other factors independently and significantly associated with higher risk
of hospitalization were taking medications at the time of ED visit, being younger
than 1 year of age and having altered liver enzyme values. Eighty-five percent of
children >15 months of age who were hospitalized were not vaccinated. One hundred
six hospitalized children (94%) had at least 1 measles complication; 1 child
required intensive care for respiratory insufficiency. CONCLUSIONS:
Hospitalizations of children with measles continue to occur in European areas
where elimination has not been achieved. Children with chronic diseases represent
a vulnerable population that is at higher risk of hospitalization.
PMID- 28426448
TI - Clinical and ethical challenges in heart transplantation from donation after
circulatory determined death donors.
AB - PURPOSE OF REVIEW: The aim of this study was to describe the development of a
clinical programme of heart transplantation from nonheart beating (or donation
after circulatory determined death, DCD) donors. DCD is an established practice
in abdominal and lung transplantation. The opportunity for sufferers of advanced
heart failure provided by DCD heart transplantation is described. RECENT
FINDINGS: Work shows that the arrested DCD heart is viable and has a 30-min
tolerance to anoxia at normal body temperature making transplantation possible.
SUMMARY: The demonstration of the possibility of DCD heart transplantation and
its early clinical success is described.
PMID- 28426449
TI - Temperature and oxygenation during organ preservation: friends or foes?
AB - PURPOSE OF REVIEW: The liberalization of donor selection criteria in organ
transplantation, with the increased use of suboptimal grafts, has stimulated
interest in ischemia-reperfusion injury prevention and graft reconditioning.
Organ preservation technologies are changing considerably, mostly through the
reintroduction of dynamic machine preservation. Here, we review the current
evidence on the role of temperature and oxygenation during dynamic machine
preservation. RECENT FINDINGS: A large but complex body of evidence exists and
comparative studies are few. Oxygenation seems to support an advantageous effect
in hypothermic machine preservation and is mandatory in normothermic machine
preservation, although in the latter, supraphysiological oxygen tensions should
be avoided. High-risk grafts, such as suboptimal organs, may optimally benefit
from oxygenated perfusion conditions that support metabolism and activate
mechanisms of repair such as subnormothermic machine preservation, controlled
oxygenated rewarming, and normothermic machine preservation. For lower risk
grafts, oxygenation during hypothermic machine preservation may sufficiently
reduce injuries and recharge the cellular energy to secure functional recovery
after transplantation. SUMMARY: The relationship between temperature and
oxygenation in organ preservation is more complex than physiological laws would
suggest. Rather than one default perfusion temperature/oxygenation standard,
perfusion protocols should be tailored for specific needs of grafts of different
quality.
PMID- 28426450
TI - IBD LIVE Series-Case 7: The Brain-Gut Connection and the Importance of Integrated
Care in IBD.
PMID- 28426451
TI - Quality of Care and Outcomes Among Hospitalized Inflammatory Bowel Disease
Patients: A Multicenter Retrospective Study.
AB - BACKGROUND: Half of patients with inflammatory bowel disease (IBD) require
hospitalization. We sought to characterize inpatient quality indicators of care
and outcomes during IBD-related hospitalizations at 4 major IBD referral centers
in Canada. METHODS: We conducted a multicenter retrospective cohort study of
patients with IBD admitted from 2011 to 2013 to tertiary centers in Toronto,
Montreal, Ottawa, and Vancouver. We assessed the following inpatient indicators
of care: pharmacological venous thromboembolism (VTE) prophylaxis, Clostridium
difficile testing, and medical rescue therapy for steroid-refractory ulcerative
colitis (UC). We also evaluated rates of VTE, C. difficile infection, and IBD
related surgery. RESULTS: There were 837 patients hospitalized for IBD (Crohn's
disease, 59%; UC, 41%). The proportion of patients with IBD who received VTE
prophylaxis and C. difficile testing were 77% and 82%, respectively, although
these indicators varied significantly by center and admitting specialty. Patients
admitted under surgeons were more likely than those admitted under
gastroenterologists to receive VTE prophylaxis (84% versus 74%, P = 0.016) but
less likely to be tested for C. difficile (41% versus 88%, P < 0.0001). The rate
of VTE was the same for those who did and did not receive VTE prophylaxis (2.2
per 1000 hospital-days). Among the 14 VTE events, 79% had received prophylaxis,
but only 36% within 24 hours of admission. Among steroid-refractory UC patients,
70% received rescue therapy within 7 days of steroid initiation. The proportion
of patients with UC and CD who required respective bowel surgery was 18% and 20%,
respectively. CONCLUSIONS: There are opportunities to optimize quality of care
among hospitalized patients with IBD.
PMID- 28426452
TI - Defining the Most Appropriate Delivery Mode in Women with Inflammatory Bowel
Disease: A Systematic Review.
AB - INTRODUCTION: High cesarean section (CS) rates are observed in patients with
inflammatory bowel disease (IBD), but limited data are available to support this
decision. We conducted a comprehensive review to evaluate the most appropriate
mode of delivery in women with IBD according to disease phenotype and activity,
as well as surgical history. MATERIALS AND METHODS: We searched MEDLINE (source
PubMed) and international conference abstracts, and included all studies that
evaluated digestive outcome after delivery in patients with IBD. RESULTS: A total
of 41 articles or abstracts were screened, and 18 studies were considered in this
review, with sample sizes ranging from 4 to 229 patients and follow-up ranging
from 2 months to 7.7 years. Pooled CS rates in patients without Perianal Crohn's
disease (PCD), healed PCD or active PCD, were 27%, 43%, and 46%, respectively.
Regarding the median rate of new PCD (3.0% [IQR, 1.5-11.5] versus 6.5% [0-19.7])
or PCD recurrence (13.5% [3.2-32.7] versus 45% [0-58]), no increase was observed
in patients with vaginal delivery compared to CS, but for patients with an active
disease, worsening of symptoms was noted in two-thirds of cases. Episiotomy,
perianal tears, and instrumental delivery did not influence the incidence of PCD.
In patients with ileal pouch anal anastomosis, uncomplicated vaginal delivery
seemed to moderately influence pouch function, with no significant difference in
terms of overall continence, daytime, or night-time stool frequency, or
incontinence. However, these parameters seemed negatively impacted by a
complicated vaginal delivery. CONCLUSIONS: New long-term data from well-designed
studies are needed, but our review suggests that systematic CS in patients
suffering from IBD should probably be limited to women at risk of perineal tears
and obstetric injuries, with an active PCD, or with ileal pouch anal anastomosis.
PMID- 28426453
TI - Indications for Mode of Delivery in Pregnant Women with Inflammatory Bowel
Disease.
AB - BACKGROUND: Reasons for the increased incidence of cesarean delivery among women
with inflammatory bowel disease remain unclear. We assessed cesarean delivery
incidence and factors influencing mode of delivery in women with inflammatory
bowel disease. METHODS: We performed a 10-year retrospective cohort study of
nulliparous women who delivered a singleton infant at our institution. We
compared the risk of each mode of delivery in women with Crohn's disease and
ulcerative colitis with women without inflammatory bowel disease. We assessed
mode of delivery indications for patients with inflammatory bowel disease and
whether cesarean deliveries were planned. RESULTS: The overall incidence of
cesarean delivery among women with Crohn's disease (24/59; 40.7%) was similar to
that among women without inflammatory bowel disease (7868/21,805; 36.1%) (risk
ratio 1.1 [95% confidence interval, 0.83, 1.5]; P = 0.46), but was increased in
the subgroups with active and inactive perianal disease (risk ratio 2.3; P <
0.01). Women with ulcerative colitis had a 1.8-fold increased relative risk of
cesarean delivery (41/65; 63.1%) (95% confidence interval, 1.5, 2.1; P < 0.01),
with highest incidence in patients with ileal pouch-anal anastomosis. Forty-nine
percent of ulcerative colitis and 66.7% of Crohn's disease cesarean deliveries
were unplanned, with only 1 unplanned delivery performed for active inflammatory
bowel disease. Most unplanned deliveries were for arrest of descent/dilation and
nonreassuring fetal heart tracings. Seventy-five percent of planned cesarean
deliveries were for inflammatory bowel disease-related indications. CONCLUSIONS:
Women with ulcerative colitis and perianal Crohn's disease have an increased
incidence of cesarean delivery. At least half of cesarean deliveries are
unplanned.
PMID- 28426454
TI - Delivery Mode in Pregnant Patients with IBD: Uncertainty Remains.
PMID- 28426455
TI - Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related
Cytokines.
AB - BACKGROUND: Digoxin, a cardiac glycoside used for the treatment of heart failure,
was reported to inhibit the retinoid-related orphan receptor gamma t (RORgammat)
and attenuate the severity of experimental autoimmune encephalomyelitis and
arthritis in mice. However, the effects of digoxin in a mice model of
inflammatory bowel disease have not been elucidated. METHODS: Colitis was induced
in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T
cells. Digoxin or a vehicle was injected into mice with colitis intraperitoneally
every other day and changes in body weight were evaluated. After 6 to 8 weeks,
the treated mice were killed and evaluated for histological score, T-cell subset,
and cytokine messenger RNA (mRNA) expression in the colonic tissue. RESULTS:
Wasting disease and histological damage were significantly attenuated in digoxin
treated mice with colitis compared with those in the vehicle-treated mice. In
addition, the mRNAs of Th17-related cytokines were downregulated, whereas those
of interleukin-10 were upregulated in the colonic mucosa of digoxin-treated mice.
However, unexpectedly, the mRNA expression level of tumor necrosis factor alpha
did not decrease in the colonic mucosa of digoxin-treated mice with colitis. This
observation suggests that digoxin may ameliorate colitis by a tumor necrosis
factor alpha-independent pathway. CONCLUSIONS: This study has shown for the first
time that treatment with digoxin can ameliorate murine experimental colitis. This
finding suggests that the suppression of Th17 using reagents such as digoxin
could be effective in treating Crohn's disease refractory to anti-tumor necrosis
factor alpha therapy.
PMID- 28426456
TI - Expression and Localization of miR-21 and miR-126 in Mucosal Tissue from Patients
with Inflammatory Bowel Disease.
AB - BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that guide degradation of
mRNA and regulate protein expression. miRNA based diagnostic biomarkers for
ulcerative colitis (UC) and Crohn's disease (CD) are emerging but information
about the cellular localization of many miRNAs is limited and more detailed
histologic evaluation of miRNA expression patterns is needed to understand their
immunobiological function. METHODS: Formalin-fixed paraffin-embedded colon
biopsies from 10 patients with UC and 8 patients with CD together with 9 controls
were examined by RT-qPCR and quantitative in situ hybridization (ISH). The
cellular expression of miR-21 positive cells was further characterized using
immunohistochemical cellular markers. RESULTS: Increased levels of miR-21 and miR
126 were found in UC compared with controls and increased levels of miR-21 were
observed in UC compared with CD by both RT-qPCR and quantitative in situ
hybridization. miR-126 was localized to endothelial cells and miR-21 to cells in
the lamina propria. Multiplex immunohistochemical staining showed miR-21
expression in subsets of CD68 macrophages and CD3 T cells in UC, however, far the
majority of the miR-21 positive cells could not be categorized among CD68, CD3,
and CD19 cells. CONCLUSIONS: This study shows that miR-126 levels are increased
in UC and expressed in endothelial cells. miR-21 is expressed in subsets of
monocytes/macrophages and T cells and may work as a potential biomarker to
distinguish UC from CD. Quantitative in situ hybridization may be a powerful tool
for such analysis as it combines overall expression with validation of cellular
origin. Studies in larger cohorts may confirm this for clinical diagnostics.
PMID- 28426457
TI - Race Differences in Initial Presentation, Early Treatment, and 1-year Outcomes of
Pediatric Crohn's Disease: Results from the ImproveCareNow Network.
AB - BACKGROUND: Racially disparate care has been shown to contribute to suboptimal
health care outcomes for minorities. Using the ImproveCareNow network, we
investigated differences in management and outcomes of pediatric patients with
Crohn's disease at diagnosis and 1-year postdiagnosis. METHODS: ImproveCareNow is
a learning health network for pediatric inflammatory bowel disease. It contains
prospective, longitudinal data from outpatient encounters. This retrospective
study included all patients with Crohn's disease <=21 years, September 2006 to
October 2014, with the first recorded encounter <=90 days from date of diagnosis
and an encounter 1 year +/-60 days. We examined the effect of race on remission
rate and treatment at diagnosis and 1 year from diagnosis using t-tests, Wilcoxon
rank-sum tests, chi statistic, and Fisher's exact tests, where appropriate,
followed by univariate regression models. RESULTS: Nine hundred seventy-six
patients (Black = 118 (12%), White = 858 (88%), mean age = 13 years, 63% male)
from 39 sites were included. Black children had a higher percentage of Medicaid
insurance (44% versus 11%, P < 0.001). At diagnosis, Black children had more
active disease according to physician global assessment (P = 0.027), but not by
short Pediatric Crohn's Disease Activity Index (P = 0.67). Race differences in
treatment were not identified. Black children had lower hematocrit (34.8 versus
36.7, P < 0.001) and albumin levels (3.6 versus 3.9, P = 0.001). At 1 year, Black
children had more active disease according to physician global assessment (P =
0.016), but not by short Pediatric Crohn's Disease Activity Index (P = 0.06).
CONCLUSIONS: Black children with Crohn's disease may have more severe disease
than White children based on physician global assessment. Neither disease
phenotype differences at diagnosis nor treatment differences at 1-year follow-up
were identified.
PMID- 28426458
TI - Anti-TNFalpha Treatment After Surgical Resection for Crohn's Disease Is Effective
Despite Previous Pharmacodynamic Failure.
AB - BACKGROUND: The outcome of patients with Crohn's disease who failed anti-tumor
necrosis factor alpha (anti-TNFalpha) therapy despite adequate serum drug levels
(pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients
who underwent intestinal resection and were re-treated with the same anti
TNFalpha agent postoperatively. METHODS: Pediatric patients with Crohn's disease
who underwent intestinal resection and were treated with anti-TNFalpha agents
postoperatively were assessed retrospectively. Patients were stratified to those
with preoperative anti-TNFalpha pharmacodynamic failure and those with no
preoperative anti-TNFalpha treatment. RESULTS: A total of 53 children were
included, 18 with pharmacodynamic failure and 35 controls. Median age at
intestinal resection was 14.8 years with 23 (43%) girls. The median time from
intestinal resection to anti-TNFalpha initiation was 8 months (interquartile
range 4-14 months). At the time of postoperative anti-TNFalpha initiation there
were no differences in clinical, laboratory, and anthropometric measures between
groups. Similar proportions of patients from both groups were in clinical
remission on anti-TNFalpha treatment after 12 months and at the end of follow-up
(1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus
80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No
significant differences were observed at 14 weeks and 12 months of postoperative
anti-TNFalpha treatment including endoscopic remission rate and fecal
calprotectin. Both groups significantly improved all measures during
postoperative anti-TNFalpha treatment. CONCLUSIONS: Pediatric patients with
Crohn's disease who failed anti-TNFalpha therapy despite adequate drug levels and
underwent intestinal resection can be re-treated with the same agent for
postoperative recurrence with high success rate similar to that of anti-TNFalpha
naive patients.
PMID- 28426459
TI - The Association Between CMV Viremia or Endoscopic Features and Histopathological
Characteristics of CMV Colitis in Patients with Underlying Ulcerative Colitis.
AB - BACKGROUND: Cytomegalovirus (CMV) infection has been shown to be related to
severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this
study was to evaluate the endoscopic and pathological characteristics of CMV
colitis in patients with UC and to assess the predictive value of the endoscopic
and pathological features of CMV colitis. METHODS: A total of 50 consecutive UC
patients with CMV infection who were admitted to Peking Union Medical College
Hospital from 2010 to 2015 were enrolled in this study. RESULTS: Twenty-five UC
patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff
value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq
polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%,
respectively. A higher proportion of endoscopic punched-out ulcers, irregular
ulcers, and cobblestone-like appearance were observed among the patients in the
CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%,
60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of
CMV inclusion bodies per high-power field was significantly higher in those with
punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of
pathological inflammation was observed in the CMV colitis group than in the
control group (68.0% versus 44.0%). CONCLUSIONS: Characteristic endoscopic
features with punch-out ulcers and high CMV viremia load may be useful for
predicting the presence of CMV colitis in histology. Punch-out ulcers were found
to be associated with a higher number of inclusion bodies on histology,
suggesting a role of targeted biopsy for endoscopist.
PMID- 28426460
TI - Is Mesalamine Effective for the Induction of Remission in Crohn's Disease?
PMID- 28426461
TI - Reply.
PMID- 28426462
TI - High-resolution esophageal manometry: interpretation in clinical practice.
AB - PURPOSE OF REVIEW: Esophageal high-resolution manometry (HRM) is the current
state-of-the-art diagnostic tool to evaluate esophageal motility patterns and, as
such, is widely adopted in clinical practice. This article will review the
interpretation of esophageal HRM in clinical practice. RECENT FINDINGS: HRM uses
a high-resolution catheter to transmit intraluminal pressure data that are
subsequently converted into dynamic esophageal pressure topography (EPT) plots.
Metric data from EPT plots are synthesized to yield an esophageal motility
diagnosis according to the Chicago Classification, a formal analytic scheme for
esophageal motility disorders, which is currently in version 3.0. The standard
HRM protocol consists of a baseline phase and a series of 10 wet swallows in the
supine or reclined position. In addition, data from swallows in the seated
position and provocative HRM maneuvers provide useful information about motility
properties. Combined high-resolution impedance technology is also clinically
available and enables concurrent assessment of bolus transit and postprandial
responses. Finally, there is ongoing interest to optimize the training and
competency assessment for interpretation of HRM in clinical practice. SUMMARY:
Esophageal HRM is a valuable and sophisticated clinical tool to evaluate
esophageal motility patterns. Emerging clinical applications of esophageal HRM
include combined impedance technology, provocative maneuvers, and postprandial
evaluation.
PMID- 28426463
TI - Treatments for achalasia in 2017: how to choose among them.
AB - PURPOSE OF REVIEW: To review recent advances in achalasia diagnostics and
therapeutics. RECENT FINDINGS: The cardinal feature of achalasia, impaired lower
esophageal sphincter (LES) relaxation, can occur in association with varied
patterns of esophageal contractility. The Chicago Classification distinguishes
among these as follows: without contractility (type I), with panesophageal
pressurization (type II), with premature (spastic) distal esophageal contractions
(type III), or even with preserved peristalsis [esophagogastric junction (EGJ)
outlet obstruction]. Physiological testing also reveals achalasia-like syndromes
that also benefit from achalasia therapies. Coincident with this has been the
development of peroral endoscopic myotomy (POEM), an endoscopic technique for
performing an esophageal myotomy. Hence, the option now exists to either
selectively ablate the LES (pneumatic dilation, laparoscopic Heller myotomy, or
POEM) or to ablate the sphincter and create a myotomy along some or the entire
adjacent smooth muscle esophagus (POEM). Each achalasia syndrome has unique
treatment considerations; type II achalasia responds well to all therapies,
whereas type III responds best to POEM. SUMMARY: Emerging data support the
concept that optimal management of achalasia is phenotype-specific, guided by
high-resolution manometry, and, in some instance, functional luminal imaging
probe studies. This opinion article reviews the varied characteristic and
treatment considerations of achalasia syndromes as currently understood.
PMID- 28426464
TI - Comparative effectiveness in urology: a state of the art review utilizing a
systematic approach.
AB - PURPOSE OF REVIEW: Comparative effectiveness research plays a vital role in
healthcare delivery by guiding evidence-based practices. We performed a state-of
the-art review of comparative effectiveness research in the urology literature
for 2016, utilizing a systematic approach. Seven high-impact papers are reviewed
in detail. RECENT FINDINGS: Across the breadth of urology, there were several
important studies in comparative effectiveness research, of which we will
highlight two randomized controlled trials and five observational trials:
radiotherapy, prostatectomy, and active monitoring have equivalent mortality
outcomes in patients with localized prostate cancer; the ideal modality of
patient education is yet to be determined, and written education has minimal
effect on patient perception of prostate specific antigen screening; robotic
prostatectomy is associated with higher perioperative complication rates on a
population basis; racial disparities exist in incontinence rates after treatment
for localized prostate cancer, but not in irritative, bowel, or sexual function;
androgen deprivation therapy is associated with higher fracture, peripheral
artery disease, and cardiac-related complications than bilateral orchiectomy;
robotic and open cystectomy offer comparable cancer-specific mortality and
perioperative outcomes; and bonuses for low-cost hospitals can inadvertently
reward low-quality hospitals. SUMMARY: There have been major advancements in
comparative effectiveness research in urology in 2016.
PMID- 28426465
TI - Neoadjuvant treatment: a novel standard?
AB - PURPOSE OF REVIEW: The aim of this study was to summarize developments in the
adjuvant/neoadjuvant chemotherapy of high-risk adult-type soft tissue sarcomas
(STS). RECENT FINDINGS: The role of adjuvant/neaodjuvant chemotherapy in these
patients is controversial, with a meta-analysis suggesting a 10% survival
benefit. Recently, a randomized controlled trial in high-risk STS of extremities
and trunk wall showed a 20% improvement in progression-free and overall survival
after three preoperative cycles of epirubicin along with ifosfamide compared with
a histology-tailored chemotherapy. This study has major strengths, including the
selected high-risk population and the full-dose chemotherapy regimen. However,
this was an interim analysis with a short follow-up in a trial originally planned
to test the superiority of a histology-driven chemotherapy. As to high-risk
patient selection, the new AJCC TNM staging system adds primary tumour site as a
stratifying factor, while available prognostic nomograms account for additional
criteria. SUMMARY: A recent trial strengthens perioperative chemotherapy as an
option for high-risk STS patients within a shared decision-making process. If the
final analysis of this trial confirms the currently observed progression-free and
overall survival benefits, perioperative chemotherapy may become a standard.
Also, new staging tools may refine our ability to select patients with a risk
high enough as to deserve chemotherapy.
PMID- 28426467
TI - Neuron-Specific Enolase Predicts Poor Outcome After Cardiac Arrest and Targeted
Temperature Management: A Multicenter Study on 1,053 Patients.
AB - OBJECTIVE: Outcome prediction after cardiac arrest is important to decide on
continuation or withdrawal of intensive care. Neuron-specific enolase is an
easily available, observer-independent prognostic biomarker. Recent studies have
yielded conflicting results on its prognostic value after targeted temperature
management. DESIGN, SETTING, AND PATIENTS: We analyzed neuron-specific enolase
serum concentrations 3 days after nontraumatic in-hospital cardiac arrest and out
of-hospital cardiac arrest and outcome of patients from five hospitals in
Germany, Austria, and Italy. Patients were treated at 33 degrees C for 24 hours.
Cerebral Performance Category was evaluated upon ICU discharge. We performed case
reviews of good outcome patients with neuron-specific enolase greater than 90
MUg/L and poor outcome patients with neuron-specific enolase less than or equal
to 17 MUg/L (upper limit of normal). MEASUREMENTS AND MAIN RESULTS: A neuron
specific enolase serum concentration greater than 90 MUg/L predicted Cerebral
Performance Category 4-5 with a positive predictive value of 99%, false positive
rate of 0.5%, and a sensitivity of 48%. All three patients with neuron-specific
enolase greater than 90 MUg/L and Cerebral Performance Category 1-2 had
confounders for neuron-specific enolase elevation. An neuron-specific enolase
serum concentration less than or equal to 17 MUg/L excluded Cerebral Performance
Category 4-5 with a negative predictive value of 92%. The majority of 14 patients
with neuron-specific enolase less than or equal to 17 MUg/L who died had a cause
of death other than hypoxic-ischemic encephalopathy. Specificity and sensitivity
for prediction of poor outcome were independent of age, sex, and initial rhythm
but higher for out-of-hospital cardiac arrest than for in-hospital cardiac arrest
patients. CONCLUSION: High neuron-specific enolase serum concentrations reliably
predicted poor outcome at ICU discharge. Prediction accuracy differed and was
better for out-of-hospital cardiac arrest than for in-hospital cardiac arrest
patients. Our "in-the-field" data indicate 90 MUg/L as a threshold associated
with almost no false positives at acceptable sensitivity. Confounders of neuron
specific enolase elevation should be actively considered: neuron-specific enolase
producing tumors, acute brain diseases, and hemolysis. We strongly recommend
routine hemolysis quantification. Neuron-specific enolase serum concentrations
less than or equal to 17 MUg/L argue against hypoxic-ischemic encephalopathy
incompatible with reawakening.
PMID- 28426468
TI - Indwelling tunneled pleural catheters for the management of hepatic hydrothorax.
AB - PURPOSE OF REVIEW: Hepatic hydrothorax is a complication of end-stage liver
disease that may have significant associated morbidity. Sodium restriction and
diuretic therapy are the mainstays of treatment, though up to a quarter of
patients will become refractory to this and will require a pleural drainage
procedure. Thoracentesis, transjugular intrahepatic portosystemic shunt, and
chemical pleurodesis all have variable success rates and associated complications
in the management of hepatic hydrothorax. Indwelling tunneled pleural catheters
(ITPC) have been successfully used to manage recurrent symptomatic malignant
pleural effusions, and there is growing interest regarding their use in the
management of hepatic hydrothorax. RECENT FINDINGS: Evidence regarding the use of
ITPC for nonmalignant pleural effusions has been limited to retrospective studies
and small feasibility trials. A recent meta-analysis regarding the use of IPTC
for nonmalignant pleural effusions demonstrated a rate of spontaneous pleurodesis
of 51%, whereas a small, prospective study demonstrated spontaneous pleurodesis
rates of 33% and an infection rate of 16.7% in 24 patients with ITPC placed for
hepatic hydrothorax in patients suitable for liver transplant evaluation.
SUMMARY: ITPC may be an acceptable treatment option for the management of hepatic
hydrothorax which are refractory to conventional medical management. Larger,
randomized controlled trials are needed to further evaluate the safety and
efficacy of these catheters for the management of nonmalignant pleural effusions.
PMID- 28426466
TI - Physician Variation in Time to Antimicrobial Treatment for Septic Patients
Presenting to the Emergency Department.
AB - OBJECTIVES: Delayed initiation of appropriate antimicrobials is linked to higher
sepsis mortality. We investigated interphysician variation in septic patients'
door-to-antimicrobial time. DESIGN: Retrospective cohort study. SETTING:
Emergency department of an academic medical center. SUBJECTS: Adult patients
treated with antimicrobials in the emergency department between 2009 and 2015 for
fluid-refractory severe sepsis or septic shock. Patients who were transferred,
received antimicrobials prior to emergency department arrival, or were treated by
an attending physician who cared for less than five study patients were excluded.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We employed multivariable
linear regression to evaluate the association between treating attending
physician and door-to-antimicrobial time after adjustment for illness severity
(Acute Physiology and Chronic Health Evaluation II score), patient age,
prehospital or arrival hypotension, admission from a long-term care facility,
mode of arrival, weekend or nighttime admission, source of infection, and trainee
involvement in care. Among 421 eligible patients, 74% received antimicrobials
within 3 hours of emergency department arrival. After covariate adjustment,
attending physicians' (n = 40) median door-to-antimicrobial times varied
significantly, ranging from 71 to 359 minutes (p = 0.002). The percentage of each
physician's patients whose antimicrobials began within 3 hours of emergency
department arrival ranged from 0% to 100%. Overall, 12% of variability in
antimicrobial timing was explained by the attending physician compared with 4%
attributable to illness severity as measured by the Acute Physiology and Chronic
Health Evaluation II score (p < 0.001). Some but not all physicians started
antimicrobials later for patients who were normotensive on presentation (p =
0.017) or who had a source of infection other than pneumonia (p = 0.006). The
adjusted odds of in-hospital mortality increased by 20% for each 1 hour increase
in door-to-antimicrobial time (p = 0.046). CONCLUSIONS: Among patients with
severe sepsis or septic shock receiving antimicrobials in the emergency
department, door-to-antimicrobial times varied five-fold among treating
physicians. Given the association between antimicrobial delay and mortality,
interventions to reduce physician variation in antimicrobial initiation are
likely indicated.
PMID- 28426469
TI - Prophylactic radiotherapy for procedure tract metastases in mesothelioma: a
review.
AB - PURPOSE OF REVIEW: Malignant pleural mesothelioma is an aggressive malignancy
with a very poor prognosis. The majority of patients require pleural procedures
for diagnostic or fluid management purposes. Damage to the pleura during these
procedures can lead to procedure tract metastases (PTMs), with increasing risk
from larger interventions. Prophylactic radiotherapy to these sites is a
controversial topic with conflicting results from trial data. In this review, we
summarize the recent evidence. RECENT FINDINGS: Four RCTs have been published on
this topic, with another in follow-up. The earliest, from a cohort of 40
patients, strongly advocated the use of prophylactic radiotherapy. More recent
trials, most notably the Surgical and large bore procedures in Malignant pleural
mesothelioma And Radiotherapy Trial (SMART) (which randomized over 200 patients)
did not demonstrate any benefit, especially when patient report symptoms and cost
effectiveness are considered. Certain subgroups demand further investigation,
such as those not receiving systematic chemotherapy or with surgical intervention
sites. The soon to be published Prophylactic Irradiation of Tracts (PIT) trial
may help to further clarify best practice. SUMMARY: Recent studies have shown
that prophylactic radiotherapy should not be routinely used to prevent PTMs in
mesothelioma. Instead patients should undergo careful clinical follow-up to
ensure PTMs are identified and treated promptly to minimize symptoms.
PMID- 28426470
TI - Identification and management of pleural effusions of multiple aetiologies.
AB - PURPOSE OF REVIEW: Historically, pleural effusions have been attributed to a
single cause. There is growing recognition that a substantial proportion of
pleural effusions may have more than one underlying cause. The purpose of this
review is to summarise recent findings regarding the diagnosis and treatment of
effusions secondary to more than one aetiology. RECENT FINDINGS: A recent
prospective study identified that 30% of pleural effusions had more than one
underlying aetiology. With a rising prevalence of cardiovascular and malignant
disease, the incidence of the complex pleural patient is increasing. The use of
biomarkers, including pro-B-type natriuretic peptide, have been suggested as a
way of identifying contributing disease process. SUMMARY: Understanding that
there are potentially concurrent causes to a pleural effusion is vital in
establishing the diagnoses of multiple underlying aetiologies. New diagnostic
pathways, with increasing use of biomarkers, will be required to identify the
complex pleural effusion. Further studies on whether the targeting of separate
aetiologies improves outcomes will help develop future management strategies.
PMID- 28426471
TI - Advances in the management of malignant pleural effusion.
AB - PURPOSE OF REVIEW: The current review describes the latest evidence in the
management of malignant pleural effusions (MPE). RECENT FINDINGS: Daily drainage
of indwelling pleural catheters achieved auto-pleurodesis at a higher rate
compared with every-other-day drainage [0.47 vs. 0.24; difference in proportion
of 0.23; 95% confidence interval (CI) 0.08-0.38; P = 0.003]. In patients with MPE
undergoing talc pleurodesis, a large multicenter randomized clinical trial found
that pain control with opiates vs. nonsteroidal anti-inflammatory drugs (NSAID)
group were not significantly different (mean visual analog scale of 23.8 vs. 22.1
mm, respectively, adjusted difference -1.5 mm; 95% CI 1.3-3.4; P = 0.40). NSAID
use was found to be noninferior to opiates with respect to the rate of
pleurodesis failure at 3-month follow-up (prespecified noninferiority margin 15%,
failure rates 20% opiates vs. 23% NSAIDS, respectively, difference -3%, 95% CI
10% to infinity; P = 0.004 for noninferiority). Talc remains the most effective
sclerosing agent based on multiple systematic reviews and meta-analyses. SUMMARY:
More prospective studies are needed to determine the optimal frequency of
indwelling pleural catheters drainage. NSAIDS can be used for pain control and do
not adversely impact the chance of successful pleurodesis.
PMID- 28426472
TI - Imaging in Patients with Crohn's Disease: Trends in Abdominal CT/MRI Utilization
and Radiation Exposure Considerations over a 10-Year Period.
AB - PURPOSE: To study the trends in utilization of computed tomography (CT) and
magnetic resonance imaging (MRI) in patients with Crohn's disease and to evaluate
changes in CT radiation exposure over a 10-year period. METHODS: In this
institutional review board-approved single-institution retrospective study, we
included patients who underwent CT and MRIs for evaluation of Crohn's disease
between 2006 and 2015. A total of 3196 CTs and 1924 MR scans were performed in
2156 patients (mean age: 34.8 +/- 17.71 yr; range: 3-91 yr) for initial diagnosis
or follow-up of Crohn's disease between 2006 and 2015. Trends in CT/MR
utilization was assessed by comparing the volume of CT/MRI studies performed each
year. The changes in CT radiation exposure over the study period were estimated
and compared. RESULTS: The annual combined CT/MR utilization demonstrated a 1.9
fold rise over the last decade (2006: n = 358, 2015: n = 681, P < 0.001, r =
0.96). It was predominantly because of a substantial growth (9.2-fold increase)
in the MR scan volume (2006: n = 37, 2015: n = 341, P < 0.001, r = 0.93), whereas
CT volume did not show significant change (2006: n = 321, 2015: n = 340, P =
0.6). Over this same period, there was a 59.4% reduction in mean radiation
exposure (2006: CT dose indexvol 16.9 +/- 7.1 mGy, 2015: CT dose indexvol 6.87 +/
4.62 mGy, P < 0.001). CONCLUSIONS: A 9-fold growth in annual MR scan volume
contributed to a nearly 2-fold rise in yearly cross-sectional imaging utilization
in Crohn's patients between 2006 and 2015. Rising trend in imaging utilization
paralleled a 60% reduction of CT radiation exposure.
PMID- 28426473
TI - Modifiable Risk Factors for Hospital Readmission Among Patients with Inflammatory
Bowel Disease in a Nationwide Database.
AB - BACKGROUND: Previous studies suggest that disease activity alone does not
reliably predict hospital readmission among patients with inflammatory bowel
diseases (IBDs). Using a national database, we aimed to further describe the
burden of readmissions for IBD and identify modifiable risk factors. METHODS: We
performed a retrospective cohort study using 2013 data from the Nationwide
Readmission Database (NRD). Using International Classification of Diseases, ninth
Revision, Clinical Modification (ICD-9-CM) codes, we identified adult patients
with discharge diagnoses of ulcerative colitis or Crohn's disease and ascertained
diagnoses of anxiety, depression, chronic pain, tobacco use, and other
comorbidities during index admission. Logistic regression was used to estimate
factors associated with hospital readmission. RESULTS: Among 52,498
hospitalizations of patients with IBD (63% Crohn's disease and 37% ulcerative
colitis), 12,407 (24%) were readmitted within 90 days of the index
hospitalization, resulting in roughly $576 million in excess charges. In
multivariable analysis of patients with Crohn's disease, anxiety (odds ratio [OR]
1.31, 95% confidence interval [CI], 1.21-1.43), depression (OR 1.27, 95% CI, 1.07
1.50), chronic pain (OR 1.31, 95% CI, 1.18-1.46), and tobacco abuse (OR 1.13, 95%
CI, 1.06-1.22) were associated with a significant increase in odds of
readmission. Among patients with ulcerative colitis, anxiety (OR 1.28, 95% CI,
1.14-1.45), depression (OR 1.35, 95% CI, 1.07-1.70), and chronic pain (OR 1.44,
95% CI, 1.21-1.73) were associated with a significant increase in odds of
readmission. CONCLUSIONS: Readmission occurs frequently in patients with IBD and
is costly. Anxiety, depression, and chronic pain may represent targets for
interventions to prevent 90-day hospital readmission in this population.
PMID- 28426475
TI - Reply to Letter to the Editor: "The HIBA Index for ALPPS, Preliminary Results to
Interpret With Caution".
PMID- 28426474
TI - Pouch-Related Symptoms and Quality of Life in Patients with Ileal Pouch-Anal
Anastomosis.
AB - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
has become the standard surgical treatment for the majority of patients with
inflammatory bowel disease (IBD) who require colectomy. We evaluated the
prevalence of pouch-related symptoms among the Crohn's and Colitis Foundation of
America Partners cohort and the effect of pouch-related symptoms on Patient
Reported Outcome Measurement Information System measures. METHODS: We performed
analyses nested in the Crohn's and Colitis Foundation of America Partners cohort.
We used bivariate analyses to compare demographics and medication use among
patients with ulcerative colitis or indeterminate colitis and pouch-related
symptoms and those with IPAA without symptoms. We also compared Patient-Reported
Outcome Measurement Information System domains (measured in T-scores) and short
IBD questionnaire quality of life scales between symptomatic pouch patients (over
the past 6 mo) and those without symptoms. RESULTS: Among 243 patients reporting
a history of IPAA, 199 (82%) reported a history of pouch symptoms. Patients with
recent pouch symptoms demonstrated higher mean T-scores in pain interference
(53.0 versus 45.3; P < 0.001), depression (51.0 versus 46.4; P = 0.002), and
fatigue (56.3 versus 47.0; P < 0.001). Symptomatic pouch patients reported lower
mean scores in social role satisfaction (47.4 versus 54.6) and short IBD
questionnaire (4.8 versus 5.8) (both P < 0.001). These differences were all
clinically meaningful. CONCLUSIONS: In a large sample of patients with IBD,
nearly all patients with IPAA reported a history of pouch symptoms. Patients
experiencing symptoms within the 6 months before the survey assessment
demonstrated clinically meaningful decrements in patient-reported outcomes in
multiple domains of physical and psychosocial functioning.
PMID- 28426477
TI - Incidence of Adhesive Bowel Obstruction After Colon Cancer Surgery and its Risk
Factors: A Nationwide Claim Study.
AB - OBJECTIVE: To elucidate the incidence of adhesive postoperative bowel obstruction
(PBO) after colon cancer surgery and its risk factors using nationwide claim
data. BACKGROUND: PBO has a significant impact on quality of life and medical
costs after colectomy, though most of the literature consists of single
institution analyses. METHODS: Data from 24,645 patients who underwent regional
colectomy for colon cancer from 2010 to 2012 and had at least 3 years of follow
up were obtained from the Health Insurance Review and Assessment Service
database. Patients who required nasogastric tube insertion or bowel obstruction
surgery more than 30 days after index colectomy were defined as having PBO.
RESULTS: A total of 3083 (12.5%) patients experienced at least one PBO episode
within 3 years after surgery. Logistic regression analysis showed that
significant risk factors for PBO were elderly (odds ratio, OR = 1.13), male (OR =
1.27), open colectomy (OR = 1.99), and low-volume institution (OR = 1.17). Among
3083 PBO patients, 50.7% experienced their 1st PBO during the 1st year after the
index colectomy, and 7.8% experienced recurrence within 3 years after index
colectomy. The 3-year cumulative incidences of PBO according to risk factors of
elderly, male, open colectomy, and low-volume institution were 14.6%, 14.3%,
19.5%, and 15.1%, respectively. CONCLUSIONS: We report several independent risk
factors for PBO and its incidence after regional colectomy for colon cancer.
These results are informative for medical providers as patients who will or have
had the procedure and could be useful baseline data for further research on the
active prevention or treatment of PBO after colectomy.
PMID- 28426476
TI - Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase
2 Randomized Placebo-controlled Study (MIAS).
AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric
injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a
controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected
to definitively cure FI by regenerating damaged sphincter. Preclinical data and
results of open-label trials suggest that myoblast therapy may represent a
noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double
blind, placebo-controlled study of intrasphincteric injections of AM in 24
patients. The study compared outcome after AM (n = 12) or placebo (n = 12)
injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months.
Patients in the placebo group were eligible to receive frozen AM after 1 year.
RESULTS: At 6 months, the median CCI score significantly decreased from baseline
in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups.
Hence, no significant difference was found between the 2 groups (primary
endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate
in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo
group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12
months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed
frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12
months. CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown
tolerance, safety, and clinical benefit at 12 months despite a transient placebo
effect at 6 months.
PMID- 28426478
TI - Advocating for a Sensible Firearm Injury Prevention Plan.
PMID- 28426480
TI - The HIBA Index for ALPPS, Preliminary Results to Interpret With Caution.
PMID- 28426479
TI - Long-term Impact of Bile Duct Injury on Morbidity, Mortality, Quality of Life,
and Work Related Limitations.
AB - OBJECTIVE: Assessment of long-term comprehensive outcome of multimodality
treatment of bile duct injury (BDI) in terms of morbidity, mortality, quality of
life (QoL), survival, and work related limitations. BACKGROUND: The impact of BDI
on work ability is scarcely investigated. METHODS: BDI patients referred to a
tertiary center after BDI were included (n = 800). QoL and work related
limitations (HLQ) were compared with 175 control patients after uncomplicated
laparoscopic cholecystectomy. RESULTS: The mean survival after BDI was 17.6 years
(95% confidence interval, CI, 17.2-18.0 years). BDI related mortality was 3.5%
(28/800). Corrected for sex, ASA classification, treatment and type of injury,
survival is worse in male patients (hazard ratio, HR 1.50, 95% CI 1.01-2.33) and
progressively worse with higher ASA classification (ASA2: 5.25 (2.94-9.37), ASA3:
18.1 (9.79-33.3). Patients treated surgically had a significantly better survival
(HR: 0.45 (95% CI: 0.25-0.80). BDI patients reported a significantly worse
physical QoL compared with the control group and worse disease specific QoL. Loss
of productivity of work was significantly higher among BDI patients. There also
was a significant hindrance in unpaid work. A higher number of bile duct injury
patients were receiving disability benefits after long-term follow-up (34.9% vs
19.6%, P = 0.004). CONCLUSIONS: Reconstructive surgery in BDI patients is
associated with improved survival. Although the clinical outcome of
multidisciplinary treatment of bile duct injury is good, it is associated with a
significant decrease in QoL, loss of productivity in both paid and unpaid work
and high rates of disability benefits use.
PMID- 28426481
TI - Response to: "Consideration of KRAS Mutation Status May Enhance the Prognostic
Impact of Indeterminate Extrahepatic Disease in the Lungs, as Identified by 18FDG
PET, in Patients With Colorectal Liver Metastases".
PMID- 28426482
TI - Legislative Strategies to Reduce the Toll of Firearm Injuries in America.
PMID- 28426483
TI - Beyond "Measure Twice": New Performance Standards in Surgery.
PMID- 28426484
TI - Connective Tissue Nevi: A Review of the Literature.
AB - Connective tissue nevi (CTN) are hamartomas of the dermis, with the 3 main
components being collagen, elastin, and proteoglycans. Each subtype can present
as a solitary lesion or multiple lesions. They could present as part of systemic
diseases or inherited disorders. This article provides a comprehensive literature
review of the different types of CTN, their clinical presentations, associations,
and treatment options. Treatment options for 56 lesions were reviewed. Fifty-two
percent of lesions were present in males, and the age range at the time of
presentation was wide (1.6-80 years). Management varied according to CTN
subtypes. Most lesions (14) received topical or intralesional treatment with
corticosteroids, followed by surgical removal of lesions (12), whereas the
remaining lesions were clinically monitored.
PMID- 28426485
TI - ALK Expression is a Rare Finding in Mycosis Fungoides.
AB - Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma.
Although indolent in its early stages, MF is more aggressive in advanced stages,
particularly if large cell transformation occurs. Histologically, transformed MF
is similar to primary cutaneous anaplastic large cell lymphoma (pcALCL) and nodal
ALCL (nALCL). MF had not been associated with immunohistochemical expression of
anaplastic lymphoma kinase (ALK) until we previously reported a case documenting
the presence of ALK by immunohistochemistry in a patient with stage IA MF and
concurrent nALCL. This is a unique finding due to the fact that ALK positivity is
usually found in nALCL. The goal of this study is to examine the extent to which
ALK may be expressed in the different morphologic lesions of MF. One hundred
three biopsies from 96 patients, including the patient from the original case,
with confirmed MF representing various lesion stages and subtypes, were tested
for ALK by immunohistochemical staining. Out of the 103 biopsies, only the
original index case of Stage IA MF with concurrent nALCL expressed ALK. From
these results, we conclude that ALK is not routinely present in MF in any lesion
stage or variant type. Routine staining of ALK is therefore of no additional
benefit for the workup of known early stage MF; however, its use may be
beneficial in the initial workup of unspecified large cell lymphomas of the skin.
PMID- 28426486
TI - Neutrophilic Figurate Erythema.
AB - Neutrophilic figurate erythema (NFE) has been rarely reported. This study aimed
to identify the clinical and pathological features of NFE. We retrospectively
reviewed the information from diagnostic cases from 2000 to 2013. The diagnosis
of NFE includes clinically annular rash, histopathologically predominant
neutrophilic perivascular and interstitial infiltrate in the dermis without
evidence of vasculitis, and exclusion of other known specific entities. Fifteen
cases of NFE were identified, including 11 women and 4 men. The age distribution
was 18-66 years (average 41). The major characteristic patterns in NFE were
blistering annular erythema (5/15 patients), purpuric annular erythema with
vesicles (4/15 patients), and multiple annular rash with central ring-shaped
scales (4/15 patients). There was no specific predicted location and no
association with a major systemic disease. Papillary dermal edema and mild-to
moderate leukocytoclasis in the upper dermis are the main histopathological
features. Ten of the 15 patients had recurrent episodes. Two patients who had
single episode were associated with drug reaction. Antineutrophil therapy was
required to control the symptoms in 3 patients. NFE has a similar clinical course
as erythema annulare centrifugum but has distinct features that can be recognized
clinically. The pathologists should be aware of the entity when making the
diagnosis of neutrophil-mediated inflammatory disorders. The treatment regimen
for neutrophilic dermatoses may be needed to manage the skin lesions.
PMID- 28426487
TI - Brief Report: HPV-17 Infection in Darier Disease With Acrokeratosis Verrucosis of
Hopf.
AB - The co-existence of Darier disease (DD) and acrokeratosis verruciformis of Hopf
(AKV) has been noted for decades and the relationship between the 2 entities
remains controversial. Although, it has been shown that both diseases are
associated with mutations in ATPA2 gene, it is yet to be determined if they are
the same disease, or separate but allelic, or interlinked in some other fashion.
Herein, the authors report the case of a 13-year-old girl presenting with shiny
flat-topped verruca plana-like papules, on the dorsal hands and feet and red
brown crusted papules on her forehead and along the sides of her neck.
Histological evaluation of a wart-like lesion shows features of AKV, a verruca
plana-like histopathology and focal acantholytic dyskeratosis. Forehead biopsy
also demonstrated focal acantholytic dyskeratosis supporting the diagnosis of DD.
Polymerase chain reaction for human papillomavirus (HPV) DNA detected HPV-17, a
human betapapillomavirus in the verruca plana-like papule. Cytoplasmic expression
of the L1 capsid expression was seen in areas of hypergranulosis. The presence of
productive betaPV infection in the setting of DD and AKV suggests a
susceptibility to HPV infection.
PMID- 28426488
TI - Melanocytes Containing Large Nuclei and Abundant Pale Cytoplasm in Melanocytic
Nevi.
PMID- 28426489
TI - A Large Congenital Blue Plaque With Papules and Nodules on the Lower Back.
PMID- 28426490
TI - Acute Necrotic Plaque in an Immunocompromised Host.
PMID- 28426491
TI - Treatment of Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia
Type 1: Some Clarity But Continued Controversy.
PMID- 28426493
TI - Clinical Features of Recurrent Acute Pancreatitis: Experience From a Single
Center.
PMID- 28426492
TI - Clinical Practice Guidelines for Pancreatic Cancer 2016 From the Japan Pancreas
Society: A Synopsis.
AB - OBJECTIVES: Clinical Practice Guidelines for Pancreatic Cancer based on Evidence
Based Medicine 2006 were first published by the Japan Pancreas Society, and they
were revised to Clinical Practice Guidelines for Pancreatic Cancer 2009 in July
2009 and were further revised to Clinical Practice Guidelines for Pancreatic
Cancer 2013 in October 2013. These guidelines were established according to
evidence-based medicine. In October 2016, the Clinical Practice Guidelines for
Pancreatic Cancer were newly revised in Japanese. METHODS: In the revised
version, we introduced the concepts of GRADE - grading recommendations
assessment, development, and evaluation approach for better understanding of the
current guidelines. RESULTS: The guidelines show algorithms for the diagnosis,
treatment, and chemotherapy of pancreatic cancer and address 7 subjects:
diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy,
stent therapy, and palliative medicine. They include 51 clinical questions and 76
statements. There are statements corresponding to clinical questions, evidence
levels, recommended strengths, and agreement rates. CONCLUSIONS: These guidelines
represent the most standard clinical and practical management at this time in
Japan. This is the English synopsis of the Clinical Practice Guidelines for
Pancreatic Cancer 2016 in Japanese, which aims to disseminate the Japanese
guidelines worldwide for the introduction of Japanese clinical management of
these diseases.
PMID- 28426494
TI - Reply to: Yang et al, Clinical Features of Recurrent Acute Pancreatitis:
Experience From a Single Center.
PMID- 28426495
TI - Biomarkers in the Differential Diagnosis of Pancreatic Diseases: Looking for a
Compass.
PMID- 28426496
TI - Successful Management of Pancreatic Kaposiform Hemangioendothelioma With
Sirolimus: Case Report and Literature Review.
PMID- 28426497
TI - The Cost of Surveying Intraductal Papillary Mucinous Neoplasms.
PMID- 28426498
TI - Pediatric Chronic Pancreatitis Due to Metabolic Disease: A Rare Etiology.
PMID- 28426499
TI - No Association Between Nonsteroidal Anti-inflammatory Drug Use and Pancreatic
Cancer Incidence and Survival.
PMID- 28426500
TI - Pancreatic Rheumatoid Nodule: Case Report and Review of the Literature.
PMID- 28426501
TI - Fluid Balance and Organ Failure in Acute Pancreatitis: Retrospective Cohort
Study.
PMID- 28426503
TI - Foreword.
PMID- 28426505
TI - Foreword.
PMID- 28426506
TI - Applications of Noninvasive Hemodynamic Monitoring in Obstetric Management.
AB - Clinicians managing obstetric patients are dependent on valid hemodynamic
measurements to guide care. Heart rate and noninvasive blood pressure guide most
current care. New hemodynamic monitors are being used to report research findings
and are being investigated by clinicians for their value to supplement standard
monitoring. These include arterial pulse contour analysis, Doppler velocimetry,
and bioimpedance among others. This chapter serves to present these new devices
with a critical review of their advantages and limitations, and most importantly
the validity of their measurements.
PMID- 28426507
TI - Peripartum Anesthetic Management of the Opioid-tolerant or Buprenorphine/Suboxone
dependent Patient.
AB - Opioid abuse and dependence continues to rise in both the general population and
pregnancy, with opioid overdose deaths having quadrupled in the last 15 years.
Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6%
documented maternal opiate use at time of birth. The management of the opioid
tolerant, buprenorphine-dependent or methadone-dependent patient in the
peripartum period is reviewed. Options for treatment of opioid dependence, acute
pain management, and perioperative multimodal analgesia are discussed. The
effects of maternal management on neonatal abstinence syndrome are also reviewed.
PMID- 28426509
TI - Log-Transformed Emg Amplitude-Power Output Relationship: Single-Leg Knee-Extensor
Versus Single-Leg Cycle Ergometry.
AB - Comparing and contrasting motor unit recruitment and activation for the same
muscles for multiple versus single-joint exercise may provide a better
understanding of neuromuscular fatigue. The purpose of this study, therefore, is
to compare the slope and y-intercept terms for the three superficial quadriceps
femoris (vastus lateralis, rectus femoris, and vastus medialis) muscles derived
from the log-transformed EMG amplitude-power output relationship between the
single-leg knee-extensor ergometry and the single-leg cycle ergometry. Ten
healthy college-aged men who engaged in regular physical activity visited the
laboratory on two occasions separated by seven days to perform either single-leg
cycle ergometry (CE) or single-leg knee-extensor ergometry (KE) in a randomized
order. For each visit, subjects performed incremental exercise until voluntary
fatigue. EMG electrodes were placed on the superficial quadriceps femoris
muscles. The slope and y-intercept terms, for each muscle, for the EMG amplitude
versus power output relationship was examined using the log-transformed model for
each subject's data. The results indicated no significant (p > 0.05) mean
differences for either slope or y-intercept terms between exercise modes and
across muscles. In addition, separate repeated measures ANOVAs were used to
determine mean differences for the slope and y-intercept values between the three
muscles. In addition, separate 2 [mode: CE or KE] * intensity [intensity: 30, 60,
and 90% of maximal workload] repeated measures ANOVAs were conducted for each
muscle. There was a significant (p < 0.05) mode * exercise intensity interaction
for each muscle. Follow-up testing indicated that in the most cases, the
normalized EMG amplitude was significantly higher for single-leg knee-extensor
ergometry than single-leg cycle ergometry. These results indicated that
incremental single-leg knee-extensor ergometry activates the superficial
quadriceps femoris muscles significantly greater than single-leg cycle ergometry.
PMID- 28426510
TI - Effect of External Loading on Force and Power Production During Plyometric Push
ups.
AB - Hinshaw, TJ, Stephenson, ML, Sha, Z, and Dai, B. Effect of external loading on
force and power production during plyometric push-ups. J Strength Cond Res 32(4):
1099-1108, 2018-One common exercise to train upper-body strength and power is the
push-up. Training at the loads that would produce the greatest power is an
effective way to increase peak power. The purpose of the current study was to
quantify the changes in peak force, peak power, and peak velocity among a
modified plyometric push-up and plyometric push-ups with or without external
loading in physically active young adults. Eighteen male and 17 female
participants completed 4 push-ups: (a) modified plyometric push-up on the knees,
(b) plyometric push-up without external loading, (c) plyometric push-up with an
external load of 5% of body weight, and (d) plyometric push-up with an external
load of 10% of body weight. Two force platforms were set up to collect vertical
ground reaction forces at the hands and feet. The modified plyometric push-up
demonstrated the lowest force, power, and velocity (5.4>= Cohen's dz >=1.2). Peak
force and force at peak velocity increased (3.8>= Cohen's dz >=0.3) and peak
velocity and velocity at peak power decreased (1.4>= Cohen's dz >=0.8) for the
push-up without external loading compared with the 2 push-ups with external
loading. No significant differences were observed for peak power among the push
ups with or without external loading (0.4>= Cohen's dz >=0.1). Although peak
power is similar with or without external loading, push-ups without external
loading may be more beneficial for a quick movement, and push-ups with external
loading may be more beneficial for a greater force production.
PMID- 28426511
TI - An Evaluation of Time-Trial-Based Predictions of V[Combining Dot Above]O2max and
Recommended Training Paces for Collegiate and Recreational Runners.
AB - Scudamore, EM, Barry, VW, and Coons, JM. An Evaluation of time-trial-based
predictions of V[Combining Dot Above]O2max and recommended training paces for
collegiate and recreational runners. J Strength Cond Res 32(4): 1137-1143, 2018
The purpose of the current study was to determine the accuracy of Jack Daniels'
VDOT Running Calculator for the prediction of V[Combining Dot Above]O2max, and
recommendations of interval and training paces (pIN and pTH) in samples of
National Collegiate Athletic Association Division 1 track athletes (ATH, n = 11)
and recreational runners (REC; n = 9). Predicted variable data were obtained
using results from indoor 5-km time-trials. Data from the VDOT Calculator were
compared with laboratory-tested V[Combining Dot Above]O2max, pace at V[Combining
Dot Above]O2max (V[Combining Dot Above]O2maxpace), and lactate threshold pace
(LTpace). Results indicated that VDOT underestimated V[Combining Dot Above]O2max
in ATH (t(10) = -6.00, p < 0.001, d = 1.75) and REC (t(8) = -8.96, p < 0.001, d =
3.44). Follow-up between-groups analysis indicated that the difference between
VDOT and V[Combining Dot Above]O2max was significantly greater in REC than in ATH
(p = 0.0031, d = 1.59). pIN was slower than V[Combining Dot Above]O2maxpace in
REC (t(8) = -4.26, p = 0.003, d = 1.76), but not different in ATH (t(10) = 0.52,
p = 0.614, d = 0.14). Conversely, pTH was faster than LTpace in ATH (t(8) =
4.17, p = 0.003, d = 1.49), but not different in REC (t(8) = 1.64, p = 0.139, d =
0.57). Practically, pTH can be confidently used for threshold training regardless
of the ability level. pIN also seemed to be accurate for ATH, but may be not be
optimal for improving V[Combining Dot Above]O2max in REC. Practitioners should
interpret VDOT with caution as it may underestimate V[Combining Dot Above]O2max.
PMID- 28426512
TI - Technology in S&C: Assessing Bodyweight Squat Technique with Wearable Sensors.
AB - Strength and conditioning (S&C) coaches offer expert guidance to help those they
work with achieve their personal fitness goals. However it is not always
practical to operate under the direct supervision of an S&C coach and
consequently individuals are often left training without expert oversight. Recent
developments in inertial measurement units (IMUs) and mobile computing platforms
have allowed for the possibility of unobtrusive motion tracking systems and the
provision of real-time individualised feedback regarding exercise performance.
These systems could enable S&C coaches to remotely monitor sessions and help
individuals record their workout performance. One aspect of such technologies is
the ability to assess exercise technique and detect common deviations from
acceptable exercise form. In this study we investigate this ability in the
context of a bodyweight (BW) squat exercise. IMUs were positioned on the lumbar
spine, thighs and shanks of 77 healthy participants. Participants completed
repetitions of BW squats with acceptable form and five common deviations from
acceptable BW squatting technique. Descriptive features were extracted from the
IMU signals for each BW squat repetition and these were used to train a technique
classifier. Acceptable or aberrant BW squat technique can be detected with 98%
accuracy, 96% sensitivity and 99% specificity when using features derived from
all 5 IMUs. A single IMU system can also distinguish between acceptable and
aberrant BW squat biomechanics with excellent accuracy, sensitivity and
specificity. Detecting exact deviations from acceptable BW squatting technique
can be achieved with 80% accuracy using a 5 IMU system and 72% accuracy when
using a single IMU positioned on the right shank. These results suggest IMU based
systems can distinguish between acceptable and aberrant BW squat technique with
excellent accuracy with a single IMU system. Identification of exact deviations
is also possible but multi-IMU systems outperform single IMU systems.
PMID- 28426513
TI - Evaluation of the Functional Movement Screen and a Novel Basketball Mobility Test
as an Injury Prediction Tool for Collegiate Basketball Players.
AB - Identifying injury risk and implementing preventive measures can assist in
reducing injury occurrence and may ultimately improve athletic performance.
Improper movement patterns often contribute to musculoskeletal (MSK) injuries.
The validity of the Functional Movement Screen (FMSTM) as an injury prediction
tool for athletes remains unclear. We designed the Basketball-Specific Mobility
Test (BMT) to represent the neuromuscular demands of basketball and identify
deficiencies that may be indicative of greater MSK injury risk while playing this
sport. The aim of this study was to examine the association of FMSTM and BMT
scores with injury occurrence in collegiate basketball players. We hypothesized
that the BMT would be a better predictor of injury risk than the FMSTM, and that
scores from both tests would have a higher association with severe MSK injuries
than minor, non-MSK injuries. One-hundred nineteen male and female collegiate
basketball players from four Upper Midwest universities were assessed pre- (PRE)
and post-season (POST) using the FMSTM and BMT. In-season injury records were
collected from the schools' athletic trainers and were classified by type and
severity. During the season, 56 of 119 players were injured, resulting in 96
total injuries. Injured athletes' PRE FMSTM scores demonstrated negligible
effects compared to uninjured athletes' PRE scores (d < 0.20), though some BMT
scores showed potentially meaningful effects (d > 0.20). While specificity of the
FMSTM and BMT to predict injury was relatively high (FMSTM 85.7-87.6; BMT 42.0
88.0), sensitivity (FMSTM 14.2-22.7; BMT 11.6-39.1), odds ratios (FMSTM 1.00
2.08; BMT 0.47-1.06), and injury prediction capacities (AUC; FMSTM 0.43-0.49; BMT
0.49-0.59) of the tests were low. Although the FMSTM and BMT may be suitable for
identifying MSK deficiencies, they do not accurately determine injury risk in
collegiate basketball players. Injury risk assessments may be improved by
targeting specific injury mechanisms and the conditions in which they occur.
PMID- 28426514
TI - Comparison of the Hang High-Pull and Loaded Jump Squat for the Development of
Vertical Jump and Isometric Force-Time Characteristics.
AB - Weightlifting movements have high skill demands and require expert coaching.
Loaded jumps have a comparably lower skill demand, but may be similarly effective
for improving explosive performance. The purpose of this study was to compare
vertical jump performance, isometric force, and rate of force development (RFD)
following a ten-week intervention employing the hang high-pull (hang-pull) or
trap-bar jump squat (jump-squat). Eighteen NCAA Division II swimmers (8 males, 10
females) with at least one year of resistance training experience volunteered to
participate. Testing included the squat jump (SJ), countermovement jump (CMJ) and
the isometric mid-thigh pull (IMTP). Vertical ground reaction forces were
analyzed to obtain jump height and relative peak power. Relative peak force, peak
RFD and relative force at five time bands were obtained from the IMTP. Subjects
were randomly assigned to either a hang-pull (n = 9) or jump-squat (n = 9)
training group and completed a ten-week, volume-equated, periodized training
program. While there was a significant main effect of training for both groups,
no statistically significant between-group differences were found (p >= 0.17) for
any of the dependent variables. However, medium effect sizes in favor of the jump
squat training group were seen in SJ height (d = 0.56) and SJ peak power (d =
0.69). Loaded jumps seem equally effective as weightlifting derivatives for
improving lower-body power in experienced athletes. Since loaded jumps require
less skill and less coaching expertise than weightlifting, loaded jumps should be
considered where coaching complex movements is difficult.
PMID- 28426515
TI - Can transcranial direct current stimulation improve muscle power in individuals
with advanced resistance training experience?
AB - The aim of this study was to investigate the effects of transcranial direct
current stimulation (tDCS) on countermovement jump performance (CMJ) in men with
advanced strength training experience. Ten healthy male subjects, with advanced
strength training and squatting exercise experience, were included. Participants
took part in an initial visit to the laboratory to complete anthropometric
measurements and CMJ kinematic test-retest reliability. Participants then
completed three experimental conditions, 48-72 hours apart, in a randomized,
double-blinded crossover design: anodal, cathodal and sham tDCS (2 mA for 20
minutes targeting the motor cortex bilaterally). Participants completed three CMJ
tests before and after each experimental condition, with one-minute recovery
interval between each test. The best CMJ in each moment was selected for
analysis. Two-way (condition by moment) repeated measures ANOVA's were performed
for CMJ height, flight time and muscular peak power. Effect sizes and
interindividual variability of tDCS responses were also analyzed. There was a
significant condition by moment interaction for all outcome measures, with a
large pre-post increase in CMJ height, flight time and muscular peak power in the
anodal condition. All the participants displayed CMJ performance improvements
after the anodal condition. There were no significant differences in both
cathodal and sham conditions. Anodal tDCS may be a valuable tool to enhance
muscle power related tasks performance, which is extremely relevant for sports
that require vertical jumping ability. Anodal tDCS may also be used to support
strength training, enhancing its effects on performance-oriented outcome
measures.
PMID- 28426516
TI - Physical Profiles of Female Academy Netball Players by Position.
AB - The purpose of this study was to evaluate the height, body mass and physical
characteristics of female academy netball players by position (centers, defenders
and shooters). Data were collected on 43 regional academy players during the
preseason period and comprised of height and body mass, and physical
characteristics (single-leg hop [SLH], squat jump [SJ], countermovement jump
[CMJ], 5- and 10-m sprint, 505 and cardiorespiratory fitness). Defenders and
shooters demonstrated significantly (p = < 0.05; d >= 1.1) greater body mass
compared to centers. Defenders demonstrated significantly (p = < 0.05; d = 1.6)
greater height compared to centers, however no significant differences were noted
between centers and shooters (p = 0.19; d = 0.7) and defenders and shooters (p =
0.70; d = 0.5). Centers performed better during the SLH left leg (p = 0.01; d =
1.0), SJ (p = 0.03; d = 1.1), CMJ (p = 0.01; d = 1.4), 5 m (p = 0.04; d >= -0.9)
and 10 m sprint (p = 0.01; d = -1.2), 505 left (p <= 0.03; d >= 1.0), 505 right
(p <= 0.03; d = 1.3), and cardiorespiratory fitness (p = 0.01; d >= 1.2),
compared to other positions. No other significant differences were observed.
These findings demonstrate that height, body mass and physical characteristics
differ between positions in female netball players, and provide normative data
for English academy netball players. Strength and conditioning coaches should
consider the specific demands on individual positions when training female
netball players.
PMID- 28426517
TI - Effects of Betaine Supplementation on Muscle Strength and Power: A Systematic
Review.
AB - Ismaeel, A. Effects of betaine supplementation on muscle strength and power: a
systematic review. J Strength Cond Res 31(8): 2338-2346, 2017-Betaine (BET) has
recently gotten much attention for its potential role as an ergogenic aid and has
become a common ingredient in peri-workout dietary supplements. The purpose of
this systematic review of the literature was to investigate the effects of BET
supplementation on muscular strength and power. A computerized literature search
of 3 databases (PubMed, MEDLINE, and Scopus) was performed. Included in the
review were randomized controlled trials that measured muscle strength, power, or
both measures in healthy participants. Quality was assessed using the PEDro
scale. Seven trials were identified, and quality assessment showed that all were
of "excellent quality." Only 2 of the studies reported increases in strength or
power after supplementation with BET. The remaining 5 studies showed no change in
any strength or power outcome measures with BET supplementation. This review
highlights the lack of evidence for a clear ergogenic effect of BET
supplementation on strength and power performance. However, because 2 studies did
identify increases of up to 24.61% on strength and power as a result of BET
supplementation, additional studies are necessary to evaluate its effectiveness.
PMID- 28426518
TI - Pathophysiologic insight into MesoAmerican nephropathy.
AB - PURPOSE OF REVIEW: Mesoamerican nephropathy (MeN) is an emerging
pathophysiological entity of Chronic kidney desease (CKD) not related to
traditional risk factors (diabetes and hypertension) that have caused thousands
of deaths in Central America, mainly in sugarcane workers. The focus of this
review is to discuss the risk factors and probable mechanisms involved in the
initiation and progression of this devastating disease. RECENT FINDINGS: Frequent
episodes of subclinical Acute kidney injury caused by repetitive heat stress,
dehydration, and strenuous work have been regarded as the main risk factors for
MeN. The combination of them chronically activates vasopressin, renin angiotensin
aldosterone system, and polyol-fructokinase pathway in the kidney. Also,
subclinical rhabdomyolysis compound the framework of the disease by exacerbating
systemic inflammation and inducing uricosuria. Exposure to nephrotoxins, high
fructose intake, and use of NSAIDs could also contribute to further accelerating
the progression of the disease. SUMMARY: The evidence supports the notion that
recurrent cycles of heat stress, dehydration, and strenuous work may cause CKD.
The chronic activation of such mechanisms likely occurs in other conditions of
reduced water intake and probably explains why the current management of CKD has
not been effective to revert or halt the progression to end-stage CKD.
PMID- 28426519
TI - Toward a universal antiretroviral regimen: special considerations of pregnancy
and breast feeding.
AB - PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are
prepared for introduction in low-income and middle-income countries (LMIC), we
consider the current evidence related to dosing, efficacy and safety during
pregnancy and breastfeeding of next-generation first-line and second-line ART
regimens proposed for imminent introduction in the global marketplace. RECENT
FINDINGS: Pregnancy pharmacokinetic considerations include potentially
insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily
darunavir dosing and the paucity of data related to tenofovir alafenamide and
dolutegravir dosing, safety and efficacy. Increasingly evidence suggests an
association with adverse birth outcomes, particularly in women conceiving on ART,
and with varying risk by drug and drug combination. Clinical trials and studies
are in progress or planned that aim to determine dosing, safety and efficacy of
several new antiretrovirals (ARVs). SUMMARY: Having a universal, highly potent
and safe ART regimen for all individuals living with HIV in LMIC including
pregnant women is clearly the most beneficial strategy to keep mothers alive and
healthy and to prevent transmission of HIV to their children. It will have to be
determined whether the use of this next generation of optimized ARVs will also
optimize health outcomes of pregnant women and their children.
PMID- 28426520
TI - Nursing Practice, Research and Education in the West: The Best Is Yet to Come.
AB - PURPOSE: This paper celebrates the 60th anniversary of the Western Institute of
Nursing, the nursing organization representing 13 states in the Western United
States, and envisions a preferred future for nursing practice, research, and
education. BACKGROUND: Three landmark calls to action contribute to transforming
nursing and healthcare: the Patient Protection and Affordable Care Act of 2010;
the Institute of Medicine report Future of Nursing: Leading Change, Advancing
Health; and the report Advancing Healthcare Transformation: A New Era for
Academic Nursing. Challenges abound: U.S. healthcare remains expensive, with
poorer outcomes than other developed countries; costs of higher education are
high; our profession does not reflect the diversity of the population; and health
disparities persist. Pressing health issues, such as increases in chronic disease
and mental health conditions and substance abuse, coupled with aging of the
population, pose new priorities for nursing and healthcare. DISCUSSION: Changes
are needed in practice, research, and education. In practice, innovative,
cocreated, evidence-based models of care can open new roles for registered nurses
and advanced practice registered nurses who have knowledge, leadership, and team
skills to improve quality and address system change. In research, data can
provide a foundation for clinical practice and expand our knowledge base in
symptom science, wellness, self-management, and end-of-life/palliative care, as
well as behavioral health, to demonstrate the value of nursing care and reduce
health disparities. In education, personalized, integrative, and technology
enabled teaching and learning can lead to creative and critical thinking/decision
making, ethical and culturally inclusive foundations for practice, ensure team
and communication skills, quality and system improvements, and lifelong learning.
CONCLUSION: The role of the Western Institute of Nursing is more relevant than
ever as we collectively advance nursing, health, and healthcare through
education, clinical practice, and research.
PMID- 28426521
TI - A History of the Western Institute of Nursing and Its Communicating Nursing
Research Conferences.
AB - BACKGROUND: The Western Institute of Nursing (WIN) celebrated its 60th
anniversary and the 50th Annual Communicating Nursing Research Conference in
April 2017. PURPOSE: The purpose of this article is to provide a brief history of
the origin, development, and accomplishments of WIN and its Communicating Nursing
Research conferences. APPROACH: Historical documents and conference proceedings
were reviewed. SUMMARY: WIN was created in 1957 as the Western Council on Higher
Education for Nursing under the auspices of the Western Interstate Commission for
Higher Education. The bedrock and enduring value system of the organization is
the interrelated nature of nursing education, practice, and research. There was a
conviction that people in the Western region of the United States needed nursing
services of excellent quality and that nursing education must prepare nurses
capable of providing that care. Shared goals were to increase the science of
nursing through research and to produce nurses who could design, conduct, and
supervise research-all to the end of improving quality nursing care. These goals
were only achieved by collaboration and resource sharing among the Western region
states and organizations. Consistent with the goals, the first research
conferences were held between 1957 and 1962. Conference content focused on
seminars for faculty teaching research, on the design and conduct of research in
patient care settings, and on identification of priority areas for research. The
annual Communicating Nursing Research conferences began in 1968 and grew over the
years to a total 465 podium and poster presentations on a wide array of research
topics-and an attendance of 926-in 2016. CONCLUSION: As WIN and its Communicating
Nursing Research conferences face the next 50 years, the enduring values on which
the organization was created will stand in good stead as adaptability,
adjustments, and collaborative effort are applied to inevitable change for the
nursing profession. It is the Western way.
PMID- 28426522
TI - Patient Safety Culture Survey in Pediatric Complex Care Settings: A Factor
Analysis.
AB - OBJECTIVES: Children with complex medical needs are increasing in number and
demanding the services of pediatric long-term care facilities (pLTC), which
require a focus on patient safety culture (PSC). However, no tool to measure PSC
has been tested in this unique hybrid acute care-residential setting. The
objective of this study was to evaluate the psychometric properties of the
Nursing Home Survey on Patient Safety Culture tool slightly modified for use in
the pLTC setting. METHODS: Factor analyses were performed on data collected from
239 staff at 3 pLTC in 2012. Items were screened by principal axis factoring, and
the original structure was tested using confirmatory factor analysis. Exploratory
factor analysis was conducted to identify the best model fit for the pLTC data,
and factor reliability was assessed by Cronbach alpha. RESULTS: The extracted,
rotated factor solution suggested items in 4 (staffing, nonpunitive response to
mistakes, communication openness, and organizational learning) of the original 12
dimensions may not be a good fit for this population. Nevertheless, in the pLTC
setting, both the original and the modified factor solutions demonstrated similar
reliabilities to the published consistencies of the survey when tested in adult
nursing homes and the items factored nearly identically as theorized.
CONCLUSIONS: This study demonstrates that the Nursing Home Survey on Patient
Safety Culture with minimal modification may be an appropriate instrument to
measure PSC in pLTC settings. Additional psychometric testing is recommended to
further validate the use of this instrument in this setting, including examining
the relationship to safety outcomes. Increased use will yield data for
benchmarking purposes across these specialized settings to inform frontline
workers and organizational leaders of areas of strength and opportunity for
improvement.
PMID- 28426523
TI - Increasing HDL-C levels with medication: current perspectives.
AB - PURPOSE OF REVIEW: To date, observational studies have repeatedly demonstrated an
inverse association between HDL cholesterol (HDL-C) levels and cardiovascular
outcomes. Although the efficacy of established HDL-modifying treatment strategies
have been examined in multiple large-scale phase III trials, findings from these
experimental studies conflict with the hypothesis that HDL-C levels are
atheroprotective. In this review, we describe the trial evidence to date, and
attempt to place these results in the broader context of recent hypotheses for
the association between HDL-C levels and clinical outcomes. RECENT FINDINGS: Both
translational and genetic studies are in line with the hypothesis that HDL-C
levels do not hold causal importance for cardiovascular risk reduction. In
addition to its possible role as a biomarker for other atherogenic lipoproteins,
efforts should be made to elucidate HDLs' role in lipoprotein flux, which is
increasingly being linked to surrogate outcomes of importance to cardiovascular
epidemiology. In the future, it will be of great importance to link this measure
of HDL functionality to clinical endpoints. SUMMARY: Although trial evidence does
not support an atheroprotective role of overall HDL-C plasma levels, HDL
function/lipoprotein flux holds great promise for the development of novel
therapeutic approaches.
PMID- 28426524
TI - Beyond cascade screening: detection of familial hypercholesterolaemia at
childhood immunization and other strategies.
AB - PURPOSE OF REVIEW: Familial hypercholesterolaemia is a common genetic disorder
that accelerates premature coronary heart disease. Although effective treatments
are available, the majority of individuals remain undiagnosed. We review new
evidence for improving the detection of familial hypercholesterolaemia. RECENT
FINDINGS: Recent studies have demonstrated that universal screening of children
for familial hypercholesterolaemia may be highly effective at the time of
immunization if combined with reverse cascade testing of adult family members,
who have a more immediate risk of a coronary event. Alerts on laboratory reports
and the application of bioinformatics to electronic health records may also be
useful for identifying familial hypercholesterolaemia in community settings.
Effective detection, diagnosis, and codification of familial
hypercholesterolaemia are essential for the development of registries. SUMMARY:
Although the cost-effectiveness of screening programs for familial
hypercholesterolaemia in childhood remains to be established, combining universal
and reverse cascade screening, complemented by opportunistic identification of
individuals in high-risk settings, use of laboratory alerts, and screening of
electronic health records are likely to have a high yield in the detection of
familial hypercholesterolaemia in the community.
PMID- 28426525
TI - GSTM1 and GSTT1 Genes are Associated With DNA Damage of p53 Gene in Coke-oven
Workers.
AB - OBJECTIVES: This study investigated whether variations in GSTT1 and GSTM1 gene
are associated with the DNA damage level of p53 gene. METHODS: We quantified
urinary 1-hydroxypyrene using high-performance liquid chromatography, and
examined the DNA damage level of p53 gene by real-time quantitative PCR in 756
coke-oven workers. Multiplex PCR was used to detect the presence or absence of
genes. RESULTS: DNA damage levels of p53 gene in the high exposure group and
intermediate exposure group were significantly higher than that of p53 gene in
the low exposure group (P < 0.01). In coke-oven workers, the DNA damage levels of
subjects with non-null genotype in GSTT1 or GSTM1 gene were significantly higher
than that of those with the null genotype (P < 0.01). CONCLUSIONS: GSTT1 and
GSTM1 may modulate DNA damage levels of p53 gene when exposed to polycyclic
aromatic hydrocarbons.
PMID- 28426526
TI - Effect of Ambient Ozone Exposure Assessed by Individual Monitors on Nasal
Function and Exhaled NO Among School Children in the Area of Thessaloniki,
Greece.
AB - OBJECTIVES: The study of short-term effects of environmental ozone exposure on
nasal airflow, lung function, and airway inflammation. METHODS: Ninety one
children-47 underwent rhinomanometry-were included. The study was carried out
during the 2013 to 2014 academic year. Activity questionnaires and personal O3
samplers were distributed and 1 week later, respiratory measurements were
performed. Daily measurements of outdoor ozone were also considered. RESULTS: A
10 MUg/m increase in weekly personal ozone exposure concentrations was associated
with a non-statistically significant 12.7% decrease in nasal inspiratory airflow
(29.4% during the high ozone period). When the outdoor exposure of the same and
the previous day were taken into account the corresponding figures were 13.48%
and 43.58% (P = 0.02). CONCLUSIONS: There is an indication for increased risk of
nasal obstruction during exposure to high ozone.
PMID- 28426527
TI - US antibiotic stewardship and penicillin allergy.
AB - PURPOSE OF REVIEW: The purpose of this review is to improve otolaryngologists'
antibiotic stewardship by detailing current approaches to penicillin allergy.
RECENT FINDINGS: Although up to 15% of hospitalized patients in the United States
have a penicillin allergy recorded on their charts, fewer than 10% of these have
a true penicillin allergy. SUMMARY: Using a combination of a detailed allergy
history, skin testing and graded-dose administration, many patients whose charts
say 'penicillin-allergic' can safely be treated with penicillin and cross
reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves
money.
PMID- 28426528
TI - Comparative Analysis of Multicolor Flow Cytometry and Immunohistochemistry for
the Detection of Disseminated Tumor Cells.
AB - Disseminating cells of a primary solid tumor may represent the origin of
metastases and relapses. We aimed at comparing the diagnostic efficacy of
multicolor flow cytometry (MFC) and morphology/immunohistochemistry (IHC) in the
detection of disseminated tumor cells in the bone marrow (BM) and body fluids of
patients with solid tumors, and in pediatric neuroblastoma cases. We investigated
72 samples retrospecively from 50 patients by MFC. Morphology/IHC data were
available in 48 cases. In the first cohort, 36 samples derived from 34 patients
with various forms of suspected and proven solid tumors and in the second cohort,
36 samples of 16 children with suspected and proven neuroblastoma were analyzed
at diagnosis or during follow-up in a 4-color setting by MFC, and the results
were compared with those obtained by IHC. In the group of various solid tumors,
we found 91% concordance between IHC and MFC, and it was 65% in the neuroblastoma
group, and 77% overall. Detection of disseminated tumor cells was found to be
more effective by MFC in de novo neuroblastoma samples (100% vs. 86%). The
advantage of MFC was even more pronounced when minimal residual disease was
evaluated (efficacy, 92% vs. 68%). In contrast, efficacy of IHC was 100% in the
group of various solid tumors, whereas it was 91% for MFC. We conclude that MFC
and IHC are both essential tools for examining infiltration of BM and body fluids
by disseminating solid tumor cells. In the case of neuroblastoma, however,
minimal residual disease detection by MFC in a hypoplastic/aplastic BM
environment was more effective than IHC, as considerably more cells could be
analyzed.
PMID- 28426529
TI - Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in
Pediatric Renal Tumors.
AB - Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can
be diagnostically challenging and only a limited number of immunohistochemical
markers have been documented to help in the diagnosis: paired box (Pax) 2 and
nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms
tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However,
the immunohistochemical expression of these markers in other PRT remains unknown.
This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of
PRT. Pax8 and Pax2 showed an identical staining pattern, and were expressed in
all (100%) WT while most CCSK were negative. All congenital mesoblastic
nephromas, metanephric stromal tumors, primitive neuroectodermal tumors,
desmoplastic small round blue cell tumors, most rhabdoid tumors, and synovial
sarcomas were negative for Pax8. NGFR was expressed in 96% of CCSK (diffuse
expression in 91%). Only a minority of WT stained for NGFR: 16% showed expression
in the blastemal and 25% in the mesenchymal components. NGFR expression was noted
in synovial sarcomas (67%, with diffuse expression seen in only 1 case, 8%),
rhabdoid tumors (19%), cellular congenital mesoblastic nephromas (13%) and
metanephric stromal tumors (12.5%). Primitive neuroectodermal tumors and
desmoplastic small round blue cell tumors were negative for NGFR. In conclusion,
Pax8/Pax2 and NGFR are sensitive markers for the diagnosis of WT and CCSK,
respectively. However, their specificity is limited by variable reactivity within
a subset of other renal neoplasms.
PMID- 28426530
TI - Intramuscular Local Anesthetic Infiltration at Closure for Postoperative
Analgesia in Lumbar Spine Surgery: A Systematic Review and Meta-Analysis.
AB - STUDY DESIGN: Systematic Review and Meta-Analysis OBJECTIVE.: To identify whether
intramuscular local anesthetic infiltration prior to wound closure was effective
in reducing postoperative pain and facilitating early discharge following lumbar
spine surgery. SUMMARY OF BACKGROUND DATA: Local anesthetic infiltration prior to
wound closure may form part of the multimodal strategy for postoperative
analgesia, facilitating early mobilization and discharge. Although there are a
number of small studies investigating its utility, a quantitative meta-analysis
of the data has never been performed. METHODS: This review was conducted
according the PRISMA statement and was registered with the PROSPERO database.
Only randomized controlled trials were eligible for inclusion. Key outcomes of
interest included time to first analgesic demand, total postoperative opiate
usage in the first 24 hours, visual analogue score (VAS) at 1, 12 and 24 hours
and postoperative length of stay. RESULTS: Eleven publications fulfilled the
inclusion criteria. A total of 438 patients were include; 212 in the control
group and 226 in the intervention group. Local anesthetic infiltration resulted
in a prolonged time to first analgesic demand (mean difference (MD) 65.88
minutes, 95% confidence interval (95% CI) 23.70 to 108.06, P.0.002) as well as a
significantly reduced postoperative opiate demand (M.D. -9.71 mg, 95% CI -15.07,
4.34, p = 0.0004). There was a small but statistically significant reduction in
postoperative visual analogue score (VAS) at 1 hour (M.D. -0.87 95%CI -1.55,
0.20, p = 0.01), but no significant reduction at 12 or 24 hours (p = 0.93 and
0.85 respectively). CONCLUSION: This systematic review and meta-analysis provides
evidence that postoperative intramuscular local anaesthetic infiltration reduces
postoperative analgesic requirements and the time to first analgesic demands for
patients undergoing lumbar spine surgery. Key research priorities include
optimization of the choice and strength of local anaesthetic agent and health
economic analyses to strengthen the case for routine use of postoperative local
anesthetics in lumbar spine surgery. LEVEL OF EVIDENCE: 1.
PMID- 28426531
TI - High-Fat Feeding Protects Mice From Ventilator-Induced Lung Injury, Via
Neutrophil-Independent Mechanisms.
AB - OBJECTIVE: Obesity has a complex impact on acute respiratory distress syndrome
patients, being associated with increased likelihood of developing the syndrome
but reduced likelihood of dying. We propose that such observations are
potentially explained by a model in which obesity influences the iatrogenic
injury that occurs subsequent to intensive care admission. This study therefore
investigated whether fat feeding protected mice from ventilator-induced lung
injury. DESIGN: In vivo study. SETTING: University research laboratory. SUBJECTS:
Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either
fed a high-fat diet for 12-14 weeks, or age-matched lean controls. INTERVENTIONS:
Anesthetized mice were ventilated with injurious high tidal volume ventilation
for periods up to 180 minutes. MEASUREMENTS AND MAIN RESULTS: Fat-fed mice showed
clear attenuation of ventilator-induced lung injury in terms of respiratory
mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation
within the lungs were not significantly attenuated nor were a host of circulating
or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix
metalloproteinase activity and levels of the matrix metalloproteinase cleavage
product soluble receptor for advanced glycation end products were significantly
attenuated in fat-fed mice. This was associated with reduced stretch-induced
CD147 expression on lung epithelial cells. CONCLUSIONS: Consumption of a high-fat
diet protects mice from ventilator-induced lung injury in a manner independent of
neutrophil recruitment, which we postulate instead arises through blunted up
regulation of CD147 expression and subsequent activation of intra-alveolar matrix
metalloproteinases. These findings may open avenues for therapeutic manipulation
in acute respiratory distress syndrome and could have implications for
understanding the pathogenesis of lung disease in obese patients.
PMID- 28426533
TI - HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell :
CD8+ cell ratio or length of efficient treatment.
AB - OBJECTIVES: HIV establishes a latent infection at different degrees within naive
(TN) or central (TCM) and effector memory (TEM) CD4 T cell. Studying patients in
whom HIV production was suppressed by combined antiretroviral therapy, our main
aim was to find which factors are related or can influence intracellular viral
reservoir in different CD4 T-cell subsets. METHODS: We enrolled 32 HIV patients
successfully treated for more than 2 years, with a CD4 T-cell count more than 500
cells/MUl and plasma viremia undetectable from at least 1 year. Proviral HIV-DNA,
the amount of cells expressing signal-joint T-cell receptor rearrangement
excision circles and telomere length were quantified by droplet digital PCR in
highly purified, sorted CD4 T-cell subsets; plasma IL-7 and IL-15 were measured
by ELISA. RESULTS: HIV-DNA was significantly lower in TN cells compared with TCM
or to TEM. Conversely, TN cells contained more signal-joint T-cell receptor
rearrangement excision circles compared with TCM or to TEM; no appreciable
changes were observed in telomere length. HIV-DNA content was significantly
higher in TN and TCM cells, but not in TEM, from patients with shorter time of
treatment, or in those with lower CD4 : CD8 ratio. CONCLUSION: Length of
treatment or recovery of CD4 : CD8 ratio significantly influences viral reservoir
in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a
better monitoring of HIV reservoir and could be useful for designing future
eradication strategies.
PMID- 28426534
TI - Age-disparate relationships and HIV incidence in adolescent girls and young
women: evidence from Zimbabwe.
AB - OBJECTIVE: Age-disparate sexual relationships with older men may drive high rates
of HIV acquisition in young women in sub-Saharan Africa, but evidence is limited.
We investigate the association between age-disparate relationships and HIV
incidence in Manicaland, Zimbabwe. DESIGN: A general-population open-cohort study
(six surveys) (1998-2013). METHODS: A total of 3746 young women aged 15-24 years
participated in consecutive surveys and were HIV-negative at the beginning of
intersurvey periods. Last sexual partner age difference and age-disparate
relationships [intergenerational (>=10 years age difference) and
intragenerational (5-9 years) versus age-homogeneous (0-4 years)] were tested for
associations with HIV incidence in Cox regressions. A proximate determinants
framework was used to explore factors possibly explaining variations in the
contribution of age-disparate relationships to HIV incidence between populations
and over time. RESULTS: About 126 HIV infections occurred over 8777 person-years
(1.43 per 100 person-years; 95% confidence interval = 1.17-1.68). Sixty-five
percent of women reported partner age differences of at least 5 years. Increasing
partner age differences were associated with higher HIV incidence [adjusted
hazard ratio (aHR) = 1.05 (1.01-1.09)]. Intergenerational relationships tended to
increase HIV incidence [aHR = 1.78 (0.96-3.29)] but not intragenerational
relationships [aHR = 0.91 (0.47-1.76)]. Secondary education was associated with
reductions in intergenerational relationships [adjusted odds ratio (aOR) = 0.49
(0.36-0.68)]. Intergenerational relationships were associated with partners
having concurrent relationships [aOR = 2.59 (1.81-3.70)], which tended to
increase HIV incidence [aHR = 1.74 (0.96-3.17)]. Associations between age
disparity and HIV incidence did not change over time. CONCLUSION: Sexual
relationships with older men expose young women to increased risk of HIV
acquisition in Manicaland, which did not change over time, even with introduction
of antiretroviral therapy.
PMID- 28426535
TI - Frailty in HIV infected people: a new risk factor for bone mineral density loss.
AB - OBJECTIVE: The study aims to assess the association between bone mineral density
(BMD) and frailty in a cohort of HIV-infected patients. DESIGN: A cross-sectional
study in an HIV outpatient unit where nearly 1000 patients are monitored.
METHODS: Study participants undergoing bone densitometry were proposed an
evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and
the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self
reported exhaustion, physical activity, grip strength, chair stands, and slow
gait. Patients' characteristics were collected from an electronic medical record.
Associations of frailty with BMD and osteoporosis were tested using multivariate
linear and logit regression models, respectively. RESULTS: In total, 175 HIV
infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty
markers, osteopenia, and osteoporosis were comparable among sexes. Despite a
younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear
regression model adjusting by age, duration of HIV follow-up, BMI, smoking
status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a
negative association of spinal and femoral BMD with frailty according to SOF
criteria in women (P < 0.05). In men, SOF-defined frailty was associated with
osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model
adjusting for age, duration of HIV follow-up, CD4 nadir, CD4 T-cell count,
tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No
significant associations were found between BMD and CHS-defined frailty.
CONCLUSION: Our study shows that frailty according to SOF criteria is associated
with low spinal BMD values in female and osteoporosis in male HIV-infected
patients.
PMID- 28426536
TI - Exploring the Interaction Between Nursing Decision Making and Patient Outcomes in
2 European Cancer Centers: A Qualitative Study.
AB - BACKGROUND: In some clinical settings, nurses have difficulty describing the
outcomes of their caring activities. Understanding the reasons for this could
help nurse leaders to improve the effectiveness and visibility of nursing
practice and safeguard nurses' working conditions. OBJECTIVE: The aims of this
study were to understand how nurses working in 2 different adult cancer centers
make healthcare decisions and assess the respective outcomes on their patients.
METHODS: Through a constructivist grounded theory approach, we involved 15
clinical cancer nurses with different experiences and educational backgrounds and
6 nurse managers, working in 2 comprehensive cancer centers, 1 in Italy and 1 in
Switzerland. Data were collected in 2 phases using 20 semistructured interviews
and 9 field observations. RESULTS: Six macrocategories emerged: interacting with
situational factors, deciding relevant interventions, using multiple decision
making approaches, evaluating interventions and reporting them, pursuing
healthcare outcomes, and clarifying professional identity and roles. Nurses'
decision-making processes varied and were influenced by various factors, which
mutually influenced one another. This process was interpreted using an
explicative theory called "dynamic decision-making adaptation." CONCLUSIONS: The
present study showed how the aims, contents, and degree of autonomy in the
nurses' decision-making process are strongly influenced by the dialectic
interaction between professional and contextual factors, such as competency and
professional identity. IMPLICATIONS FOR PRACTICE: Cancer nurses could influence
their clinical practice by developing nursing competencies that effectively
resolve patients' problems. This is a key factor that nurses govern autonomously
and therefore a responsibility that involves the entire nursing educational,
organizational, and scientific leadership.
PMID- 28426537
TI - Supportive Care Needs and Association With Quality of Life of Mexican Adults With
Solid Cancers.
AB - BACKGROUND: Patients with cancer have supportive care needs. Studies that analyze
the relationship between supportive care needs and health-related quality of life
(HRQoL) are scarce. Cultural differences in supportive care needs and perceived
QoL are also worth analyzing. OBJECTIVE: The aim of this study was to assess the
association between supportive care needs and HRQoL of Mexican adults given a
diagnosis of solid cancers. METHODS: We performed a secondary data analysis of a
cross-sectional survey of 825 adult patients with cancer treated at the Oncology
Hospital of the Mexican Institute of Social Security. The QLQ-30 from the
European Organization for Research and Treatment of Cancer served to measure
HRQoL, and the Supportive Care Needs Questionnaire was used to ascertain the
needs. The analysis included multiple linear regression models for each HRQoL
domain controlled for demographic, clinical, and social support covariates.
RESULTS: There was an association between psychological needs with low scores in
the HRQoL domains of global health, emotional functioning, and increased fatigue.
Physical and daily living needs were associated with most HRQoL domains except
the emotional domain. Patient care needs were related to low scores in the
emotional and social functioning domains. Health systems and information needs
were associated with low scores on cognitive functioning. CONCLUSIONS: Physical,
psychological, patient care, and informational needs were associated with
decreased HRQoL of Mexican patients with cancer. IMPLICATIONS FOR PRACTICE:
Healthcare providers, including nurses, are encouraged to perform routine,
comprehensive evaluations of the supportive care needs and HRQoL of patients with
solid cancers to respond in a timely manner to their needs.
PMID- 28426538
TI - Five Phases of Recovery and Rehabilitation After Allogeneic Stem Cell
Transplantation: A Qualitative Study.
AB - BACKGROUND: For patients with a hematological malignancy, allogeneic stem cell
transplantation (alloSCT) is a treatment modality that may cause a wide range of
problems. Little is known about the process of recovery and rehabilitation and
the problems that alloSCT patients are confronted with during the first-year
posttransplant. OBJECTIVE: This study explored the problems of patients during
the first year after alloSCT, to better understand the process of recovery and
rehabilitation. METHODS: In a qualitative study, hemato-oncology patients were
interviewed 1-year posttransplant. The semistructured interviews were transcribed
verbatim, coded, and analyzed using constant comparative analysis. RESULTS: Ten
participants were included until saturation of data was reached. The patients had
experienced various problems and had gone through an individual process of
recovery and rehabilitation. Nevertheless, 5 phases could be distinguished: (1)
survive, (2) on the receiving end, (3) bring under control, (4) start
recuperation, and (5) retrospection. The duration of each phase varied between
patients. CONCLUSION: Although patients experienced individual problems after
alloSCT, they all followed a common pathway. Posttransplant care might be
improved by adjusting the care to the distinct phases that the patients pass
through. IMPLICATIONS FOR PRACTICE: Nurses can play an important role in
achieving improvements in posttransplant care by adjusting care to the individual
needs of patients within the distinct phases.Future nursing research should
confirm and refine this process of recovery and rehabilitation and assess the
effects of improvement measures in alloSCT patients and in other populations.
PMID- 28426539
TI - The Effect of Cancer Patients' and Their Family Caregivers' Physical and
Emotional Symptoms on Caregiver Burden.
AB - BACKGROUND: Although there is significant evidence that the family caregivers
(FCs) of cancer patients can experience significant caregiver burden and
symptoms, less is known about the relationships between FCs and patient
characteristics that influence caregiver burden. OBJECTIVE: The purpose of this
study was to examine the effect of cancer patients' and FCs' symptoms and
demographic characteristics on caregiver burden at initiation of the patients'
radiation treatment. METHODS: Two hundred eighty-one dyads of FCs and cancer
patients who received a diagnosis of breast, prostate, melanoma, lymphoma, and
head and neck cancers were recruited at the beginning of the patients' radiation
treatment. Measures of depression, sleep disturbance, fatigue, social support,
and self-efficacy were obtained from both FCs and cancer patients. The family
caregivers were also assessed for caregiver burden. Associations between
patients' and caregivers' symptoms and demographic characteristics and caregiver
burden were investigated using multivariate analyses. RESULTS: There were
significant associations between caregiver burden and the patient-related
variables such as self-efficacy (P = .02), sleep disturbance (P = .03), and
social support (P = .04). Among FC-related variables, higher scores of depression
(P < .01), fatigue (P < .01), and symptoms (P < .01) were significantly
associated with higher caregiver burden. Being a female, either as a patient or
FC, increased the likelihood of experiencing fatigue and sleep disturbance.
CONCLUSION: Caregiver burden in FCs is influenced by interplay of patients' and
their own symptoms and problems. These interdependencies exist from the beginning
of treatment. IMPLICATIONS FOR PRACTICE: Nurses should systematically assess the
problems and symptoms of the patients and FCs and support them from the time of
diagnosis to help prevent symptom development and deterioration.
PMID- 28426540
TI - Family Functioning Predicts End-of-Life Care Quality in Patients With Cancer:
Multicenter Prospective Cohort Study.
AB - BACKGROUND: Treating patients with cancer within a family setting is the accepted
standard of care and a hallmark of end-of-life (EoL) quality of care (QoC).
OBJECTIVE: The aim of this study was to determine whether family caregiver
functioning predicts EoL QoC received by terminally ill patients with cancer.
METHODS: Family caregivers of terminally ill patients with cancer (n = 264) were
enrolled from oncology inpatient and outpatient units of 12 large hospitals
located in different regions throughout South Korea. Caregivers were administered
self-reported questionnaires about family functioning and EoL QoC at the time of
an incurable cancer diagnosis, 4 to 6 weeks later, and again 2 to 3 months later.
Family functioning and QoC were measured using the family Apgar and Quality Care
Questionnaire-End of Life scales, respectively. RESULTS: Improved adaptability to
resource sharing and attention received predicted improved family relationships
for the 3 time points. Increased participation in decision making and
communication predicted improved individualized care and family relationships for
the 3 time points. Increased affection predicted improvements in dignity
conserving care and family relationships for the 3 time points. Improved
resolution regarding sharing time and satisfaction with commitments predicted
increases in all QoC domains for the 3 time points, including dignity-conserving
care, care by healthcare professionals, individualized care, and family
relationships. CONCLUSIONS: Family functioning may contribute to improved EoL QoC
of patients with terminal cancer. IMPLICATIONS FOR PRACTICE: Patients' family
caregivers are a valued source of affection and communicative support, improving
EoL QoC. More family-oriented cancer support systems can better maintain the
effectiveness of QoC until EoL.
PMID- 28426541
TI - Transfer Between Hospitals Is a Risk Situation for Patients After Lung Cancer
Surgery.
AB - BACKGROUND: Patients with lung cancer often undergo surgery shortly after
diagnosis. Despite undergoing extensive operation, many patients are transferred
to a local hospital a few days after surgery. Transitions between different
levels of care are risky due to common medication and follow-up errors.
OBJECTIVE: The study purpose was to explore patients' experiences of transfer
between hospitals after lung cancer surgery. The study aim was to improve the
quality of transitional care. METHODS: In-depth interviews with 14 patients with
lung cancer (6 men, 8 women) were conducted in the patients' homes. Interviews
were audiotaped, transcribed, and analyzed using the hermeneutic analysis method.
RESULTS: Patients' experience of transfer between hospitals after lung cancer
surgery is one of being in a caregiver gap characterized by feeling unprepared
and uncertain, feeling unprotected and not being cared for, and suffering because
of inadequate organization. Patients are vulnerable and at risk of injury before
and during transfer, as well as after arrival at local hospitals. CONCLUSIONS:
Study findings highlight a rarely considered risk of inadequate care before,
during, and after hospital transfer of vulnerable patients. Transition between
hospitals after lung cancer surgery is a part of patient care for which there are
no policies or care plans and a time during which the borders of responsibility
between caregivers are unclear. IMPLICATIONS FOR PRACTICE: It is important to
develop guidelines for clearly defined responsibilities during transfer between
hospitals. Healthcare providers need to plan transfers with the same rigor as
they do hospital care.
PMID- 28426542
TI - The Preliminary Effects of Massage and Inhalation Aromatherapy on Chemotherapy
Induced Acute Nausea and Vomiting: A Quasi-Randomized Controlled Pilot Trial.
AB - BACKGROUND: Despite pharmacological treatment, chemotherapy-induced nausea and
vomiting (CINV) are observed in patients. OBJECTIVE: This quasi-randomized
controlled pilot study evaluated the feasibility and preliminary effects of
massage and inhalation aromatherapies on chemotherapy-induced acute
nausea/vomiting. METHODS: Seventy-five patients with breast cancer were randomly
grouped into 1 of 3 groups: massage (n = 25), inhalation (n = 25), and control (n
= 25). The patients in the massage group received 20-minute aromatherapy foot
massage, whereas those in the inhalation group received 3-minute inhalation
aromatherapy before their second, third, and fourth chemotherapy cycles. The
control group underwent only the routine treatment. A nausea, vomiting, and
retching patient follow-up form was used to evaluate nausea severity by visual
analog scale and frequency of vomiting and retching. RESULTS: The incidence of
nausea and retching was significantly higher in the control group than in the
other groups in the third and fourth chemotherapy cycles (P < .001). Furthermore,
in these 2 cycles, the incidence of nausea and retching was significantly lower
in the massage group than in the inhalation group (P < .001). Nausea severity was
significantly lower among patients in the massage and inhalation groups than in
the control group in all 3 cycles (P < .001). CONCLUSION: Nausea severity was
significantly lower in the massage and inhalation aromatherapy groups than in the
control group. Nausea and retching incidence was reduced in the aromatherapy
groups compared with that in the control group. IMPLICATIONS FOR PRACTICE:
Nonpharmacological approaches are recommended for managing CINV. Massage and
inhalation aromatherapy seems promising regarding the management of CINV.
PMID- 28426544
TI - Neonatal abstinence syndrome: where are we, and where do we go from here?
AB - PURPOSE OF REVIEW: Over the last 15 years the prevalence of neonatal abstinence
syndrome (NAS) increased almost five-fold. A considerable diversity seems to
prevail in the management of NAS. This review provides an overview of factors
affecting the expression and course of NAS, and recent developments in NAS
assessment and treatment. RECENT FINDINGS: Apart from different pharmacological
and nonpharmacological treatment modalities, maturity of the infant and genetic
variations likely are (co)responsible for interpatient variability in NAS
severity, despite similar maternal exposure. Recent efforts concerning the
further development of NAS severity scoring systems focus on the development of
brief screening measures; in addition, pupil diameter and skin conductance have
been proposed as complements to observer-rated scales. The decrease in incidence
of NAS begins in the appropriate management of medication assisted treatment of
the mother. SUMMARY: Mitigating the negative outcomes for infants affected by
NAS, their mothers and the healthcare system implies, first and foremost,
developing and implementing an organized protocol for the management of NAS, and
the homogenous use of a standardized scoring system utilizing interobserver
reliability and a guide for medication initiation, maintenance, and weaning which
is consistent with traditional methods of treatment for neonates.
PMID- 28426545
TI - Sex differences in prescription opioid use.
AB - PURPOSE OF REVIEW: Recent literature focused on prescription opioids has
neglected sex differences in use. Here, we evaluated the recent literature (since
2015) examining sex differences in prescription opioid use. RECENT FINDINGS:
Between 2015 and 2016, our review found only eight articles addressing sex
differences in prescription opioid use mostly opioid misuse in North America
among individuals with chronic pain. Risk factors included depression, pain, and
polydrug use. In addition to that review, we had the opportunity to further
address sex differences in, and risk factors for, prescription opioid use through
a community engagement program, HealthStreet. Among the sample (n = 8525, Mage =
43.7 years, 58.6% women), approximately half reported use of prescription
opioids. Women were significantly more likely to report lifetime use (54.9 vs.
42.2%; P < 0.0001) and report cancer compared with men, yet, women with cancer
had a significantly reduced risk of using opioids compared with men with cancer
(odds ratio: 0.46; 95% confidence interval, 0.36-0.59). SUMMARY: Only a few
recently published studies analyzed sex differences related to prescription
opioid use. Findings from the literature and our data suggest women are more
likely to use prescription opioids compared with men. There is limited
information on sex differences in opioid use risk factors and outcomes and more
research in this area is warranted.
PMID- 28426546
TI - Methamphetamine use and dependence in vulnerable female populations.
AB - PURPOSE OF REVIEW: The study reviews recent publications on methamphetamine use
and dependence women in term of their epidemic, physical health impact,
psychosocial impacts, and also in the identified vulnerable issues. RECENT
FINDINGS: Studies of vulnerable populations of women are wide ranging and include
sex workers, sexual minorities, homeless, psychiatric patients, suburban women,
and pregnant women, in which amphetamine type stimulants (ATSs) are the most
commonly reported illicit drug used among them. The prenatal exposure of ATS
demonstrated the small for gestational age and low birth weight; however, more
research is needed on long-term studies of methamphetamine-exposed children.
Intimate partner violence (IPV) is commonly reported by female methamphetamine
users as perpetrators and victims. However, statistics and gendered power
dynamics suggest that methamphetamine-related IPV indicates a higher chance of
femicide. Methamphetamine-abusing women often have unresolved childhood trauma
and are introduced to ATS through families or partners. SUMMARY: Vulnerable
populations of women at risk of methamphetamine abuse and dependence. Impacts on
their physical and mental health, IPV, and pregnancy have been reported
continuing, which guide that empowering and holistic substance abuse are
necessary for specific group.
PMID- 28426548
TI - The MEDEX Northwest Physician Assistant Program: A Synopsis.
PMID- 28426547
TI - Excessive internet use in young women: What are the implications?
AB - PURPOSE OF REVIEW: There are considerable gender differences in youth engaging in
excessive internet use (EIU). This review provides updates based on the recent
literature focusing on the EIU in young women to describe its implications
including what it constitutes of, its correlates, sequelae and preventive and/or
treatment strategies. RECENT FINDINGS: Definition of EIU and its
conceptualization still requires refinement. Recent studies indicate a changing
trend towards female predominance of EIU. Women also differ in their internet use
compared with men regarding their preference in the internet content and online
activities, motives of use and factors related to access to the internet,
including the device, sociocultural restrictions, etc. The correlates and
sequelae of EIU encompass psychological, physical, biological, family and social
domains that could form the basis of identifying individuals at risk and
strategizing treatment. SUMMARY: The findings indicate the need for
standardization in definition and measures of EIU for better recognition of EIU
and identification of its at-higher-risk females. Effective preventive and
treatment measures are still limited by various methodology flaws outlined here.
PMID- 28426549
TI - Patient action: as means and end for chronic pain care.
PMID- 28426551
TI - Changing pain expectations: the role of social context and communication.
PMID- 28426550
TI - Neuropathic pain after chronic nerve constriction may not correlate with chloride
dysregulation in mouse trigeminal nucleus caudalis neurons.
AB - Changes in chloride reversal potential in rat spinal cord neurons have previously
been associated with persistent pain in nerve injury and inflammation models.
These changes correlate with a decrease in the expression of the potassium
chloride transporter, KCC2, and with increases in neuronal excitability. Here, we
test the hypothesis that similar changes occur in mice with neuropathic pain
induced by chronic constriction injury of the trigeminal infraorbital nerve (CCI
ION). This model allows us to distinguish an acute pain phase (3-5 days after
injury) from a persistent pain phase (12-14 days after CCI-ION). Chronic
constriction injury of the trigeminal infraorbital nerve induced significant
decreases in mechanical pain thresholds in both the acute and persistent phases.
To estimate GABAA reversal potentials in neurons from trigeminal nucleus
caudalis, we obtained perforated patch recordings in vitro. GABAA reversal
potential decreased by 8% during the acute phase in unidentified neurons, but not
in GABAergic interneurons. However, at 12 to 14 days after CCI-ION, GABAA
reversal potential recovered to normal values. Quantitative real-time polymerase
chain reaction analysis revealed no significant changes, at either 3 to 5 days or
12 to 14 days after CCI-ION, in either KCC2 or NKCC1. These findings suggest that
CCI-ION in mice results in transient and modest changes in chloride reversal
potentials, and that these changes may not persist during the late phase. This
suggests that, in the mouse model of CCI-ION, chloride dysregulation may not have
a prominent role in the central mechanisms leading to the maintenance of chronic
pain.
PMID- 28426553
TI - Greater fear of visceral pain contributes to differences between visceral and
somatic pain in healthy women.
AB - This functional magnetic resonance imaging study addressed similarities and
differences in behavioral and neural responses to experimental visceral compared
with somatic pain stimuli and explored the contribution of fear of pain to
differences between pain modalities. In N = 22 healthy women, we assessed blood
oxygen level-dependent responses to rectal distensions and cutaneous heat stimuli
matched for perceived pain intensity. Fear of pain and pain unpleasantness were
assessed before and after scanning. Visceral pain was more fear evoking and more
unpleasant, and trial-by-trial intensity ratings failed to habituate across
trials (all interactions modality * time: P < 0.01). Differences in fear of pain
and pain intensity independently contributed to greater visceral pain
unpleasantness (combined regression model: R(2) = 0.59). We observed joint neural
activations in somatosensory cortex and frontoparietal attention network
(conjunction analysis: all pFWE <0.05), but distensions induced greater
activation in somatosensory cortex, dorsal and ventral anterior insula, dorsal
anterior and midcingulate cortices, and brainstem, whereas cutaneous heat pain
led to enhanced activation in posterior insula and hippocampus (all pFWE <0.05).
Fear of visceral pain correlated with prefrontal activation, but did not
consistently contribute to neural differences between modalities. These findings
in healthy women support marked differences between phasic pain induced by rectal
distensions vs cutaneous heat, likely reflecting the higher salience of visceral
pain. More studies with clinically relevant pain models are needed to discern the
role of fear in normal interindividual differences in the response to different
types of pain and as a putative risk factor in the transition from acute to
chronic pain.
PMID- 28426554
TI - Barking up the right tree: advancing our understanding and treatment of lymphoma
with a spontaneous canine model.
AB - PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as
an ideal model for studying the disease in humans and for developing new targeted
therapeutics for patients. Increasing interest by funding agencies, the private
sector, and multidisciplinary academic collaborations between different
disciplines and sectors now enables large knowledge gaps to be addressed and
provides additional proof-of-concept examples to showcase the significance of the
canine model. RECENT FINDINGS: The current review addresses the rationale for a
canine lymphoma model including the valuable role it can play in drug
development, serving as a link between mouse xenograft models and human clinical
trials and the infrastructure that is now in place to facilitate these studies.
Research in this field has focused on filling in the gaps to make the canine
lymphoma model more robust. These advances have included work on biomarkers,
detection of minimal residual disease, expansion of genomic and proteomic data,
and immunotherapy. SUMMARY: Incorporating pet dogs into the drug development
pipeline can improve the efficiency and predictability of preclinical models and
decrease the time and cost required for a therapeutic target to be translated
into clinical benefit.
PMID- 28426555
TI - Creating artificial lymphoid tissues to study immunity and hematological
malignancies.
AB - PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect
immune cell function and progression of disease. However, current animal models
are low throughput and a large number of human diseases are difficult to model in
animals. Animal models are less amenable to manipulation of tissue niche
components, signalling pathways, epigenetics, and genome editing than ex vivo
models. On the other hand, conventional 2D cultures lack the physiological
relevance to study precise microenvironmental interactions. Thus, artificial
tissues are being developed to study these interactions in the context of immune
development, function, and disease. RECENT FINDINGS: New bone marrow and lymph
node models have been created to, respectively, study microenvironmental
interactions in hematopoiesis and germinal center-like biology. These models have
also been extended to understand the effect of these interactions on the
progression and therapeutic response in leukemia, multiple myeloma, and lymphoma.
SUMMARY: 3D in-vitro immune models have elucidated new cellular, biochemical, and
biophysical interactions as potential regulatory mechanisms, therapeutic targets,
or biomarkers that previously could not be studied in animal models and
conventional 2D cultures. Incorporation of advanced biomaterials, microfluidics,
genome editing, and single-cell analysis tools will enable further studies of
function, driver mutations, and tumor heterogeneity. Continual refinement will
help inform the development of antibody and cell-based immunotherapeutics and
patient-specific treatment plans.
PMID- 28426556
TI - Limited transthoracic echocardiogram: "This is how I do it".
PMID- 28426558
TI - Combat surgical workload in Operation Iraqi Freedom and Operation Enduring
Freedom: The definitive analysis.
AB - BACKGROUND: Relatively few publications exist on surgical workload in the
deployed military setting. This study analyzes US military combat surgical
workload in Iraq and Afghanistan to gain a more thorough understanding of
surgical training gaps and personnel requirements. METHODS: A retrospective
analysis of the Department of Defense Trauma Registry was performed for all Role
2 (R2) and Role 3 (R3) military treatment facilities from January 2001 to May
2016. International Classification of Diseases, Ninth Revision, Clinical
Modification procedure codes were grouped into 18 categories based on functional
surgical skill sets. The 189,167 surgical procedures identified were stratified
by role of care, month, and year. Percentiles were calculated for the number of
procedures for each skill set. A literature search was performed for publications
documenting combat surgical workload during the same period. RESULTS: A total of
23,548 surgical procedures were performed at R2 facilities, while 165,619
surgical procedures were performed at R3 facilities. The most common surgical
procedures performed overall were soft tissue (37.5%), orthopedic (13.84%),
abdominal (13.01%), and vascular (6.53%). The least common surgical procedures
performed overall were cardiac (0.23%), peripheral nervous system (0.53%), and
spine (0.34%).Mean surgical workload at any point in time clearly
underrepresented those units in highly kinetic areas, at times by an order of
magnitude or more. The published literature always demonstrated workloads well in
excess of the 50th percentile for the relevant time period. CONCLUSIONS: The
published literature on combat surgical workload represents the high end of the
spectrum of deployed surgical experience. These trends in surgical workload
provide vital information that can be used to determine the manpower needs of
future conflicts in ever-changing operational tempo environments. Our findings
provide surgical types and surgical workload requirements that will be useful in
surgical training and placement of medical assets in future conflicts. LEVEL OF
EVIDENCE: Epidemiologic study, level III; Care management, level III.
PMID- 28426557
TI - Loop ileostomy versus total colectomy as surgical treatment for Clostridium
difficile-associated disease: An Eastern Association for the Surgery of Trauma
multicenter trial.
AB - OBJECTIVES: The mortality of patients with Clostridium difficile-associated
disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI)
was introduced as an alternative procedure to total colectomy (TC) for CDAD by a
single-center study. To date, no reproducible results have been published. The
objective of this study was to compare these two procedures in a multicentric
approach to help the surgeon decide what procedure is best suited for the patient
in need. METHODS: This was a retrospective multicenter study conducted under the
sponsorship of the Eastern Association for the Surgery of Trauma. Demographics,
medical history, clinical presentation, APACHE score, and outcomes were
collected. We used the Research Electronic Data Capture tool to store the data.
Mann-Whitney (continuous data) and Fisher exact (categorical data) were used to
compare TC with LI. Logistic regression was performed to determine predictors of
mortality. A propensity score analysis was done to control for potential
confounders and determine adjusted mortality rates by procedure type. RESULTS: We
collected data from 10 centers of patients who presented with CDAD requiring
surgery between July 1, 2010 and July 30, 2014. Two patients died during the
surgical procedure, leaving 98 individuals in the study. The overall mortality
was 32%, and 75% had postoperative complications. Median age was 64.5 years; 59%
were male. Concerning preoperative patient conditions, 54% were on pressors, 47%
had renal failure, and 36% had respiratory failure. When comparing TC and LI,
there was no statistical difference regarding these conditions. Univariate
preprocedure predictors of mortality were age, lactate, timing of operation,
vasopressor use, and acute renal failure. There was no statistical difference
between the APACHE score of patients undergoing either procedure (TC, 22 vs LI,
16). Adjusted mortality (controlled for preprocedure confounders) was
significantly lower in the LI group (17.2% vs 39.7%; p = 0.002). CONCLUSIONS:
This is the first multicenter study comparing TC with LI for the treatment of
CDAD. In this study, LI carried less mortality than TC. In patients without
contraindications, LI should be considered for the surgical treatment of CDAD.
LEVEL OF EVIDENCE: Therapeutic study, level III.
PMID- 28426559
TI - Computed tomography evidence of fluid in the hernia sac predicts surgical site
infection following mesh repair of acutely incarcerated ventral and groin
hernias.
AB - BACKGROUND: Mesh placement during repair of acutely incarcerated ventral and
groin hernias is associated with high rates of surgical site infection (SSI). The
utility of preoperative computed tomography (CT) in this setting is unclear. We
hypothesized that CT evidence of bowel wall compromise would predict SSI while
accounting for physiologic parameters. METHODS: We performed a 4-year
retrospective cohort analysis of 50 consecutive patients who underwent mesh
repair of acutely incarcerated ventral or groin hernias. We analyzed chronic
disease burden, acute illness severity, CT findings, operative management, and
herniorrhaphy-specific outcomes within 180 days. The primary outcome was SSI by
the Centers for Disease Control and Prevention criteria. Multiple logistic
regression was performed to identify independent predictors of SSI. RESULTS:
Eighty-four percent of all patients were American Society of Anesthesiologists
class III or IV, 28% were active smokers, and mean body mass index (BMI) was 35
kg/m. Fifty-four percent had ventral hernias, 40% had inguinal hernias, and 6%
had femoral or combined inguinal/ femoral hernias. Seventy percent of
preoperative CT scans had features suggesting bowel compromise, abdominal free
fluid, or fluid in the hernia sac. Surgical site infection occurred in 32% of all
patients (8% superficial, 24% deep or organ/space). The strongest predictors of
SSI were CT evidence of fluid in the hernia sac (odds ratio [OR], 8.3; 95%
confidence interval [CI], 1.7-41), initial heart rate 90 beats/min or greater
(OR, 6.3; 95% CI, 1.1-34), and BMI 35 kg/m or greater (OR, 5.8; 95% CI, 1.2-28).
Surgical site infection rates were significantly higher among patients who had CT
evidence of fluid in the hernia sac (56% vs. 19%, p = 0.012). CONCLUSIONS: More
than half of all patients with CT scan evidence of fluid in the hernia sac
developed an SSI. Computed tomography evidence of fluid in the hernia sac was the
strongest predictor of SSI, followed by heart rate and BMI. Together, these
parameters identify high-risk patients for whom better strategies are needed to
avoid SSI without sacrificing durability. LEVEL OF EVIDENCE: Prognostic study,
level III; Therapeutic, level IV.
PMID- 28426560
TI - Universal screening for intimate partner and sexual violence in trauma patients:
An EAST multicenter trial.
AB - BACKGROUND: A single-center trial recently demonstrated a prevalence of 14% of
intimate partner and sexual violence (IPSV) among both male and female trauma
patients, regardless of mechanism of injury. We aimed to determine if this
phenomenon was similar to rates in other trauma centers by assessing the
feasibility of universal screening and determining the prevalence and association
of IPSV with other trauma-associated comorbidities. METHODS: We designed an
Eastern Association for the Surgery of Trauma-supported multicenter, prospective
observational cohort study involving four Level I trauma centers throughout the
United States. Screening occurred from March 2015 to April 2016. We performed
universal screening of adult trauma patients using the validated HITS (Hurt,
Insult, Threaten, Scream) and SAVE (sexual violence) screening surveys. Trauma
recidivism, substance use, and mental illness were also measured and were
classified as "trauma-associated comorbidities." Chi-squared test compared
categorical variables with significance at p <0.05. Parametric data is presented
as mean +/- standard deviation. RESULTS: A total of 2,034 eligible trauma
patients were screened by clinical social workers at each site over 1 year. The
mean age was 37.05 +/- 20.32 with 63% men, 37% women, and one transgendered
participant. The overall rate of IPSV was 11.4%. The proportion of positive
screens for men was 9.3%, with variability between centers (3.8-72.7%), and for
women was 16.1% (15.3-50.0%) (p < 0.001). The transgendered patient screened
positive for IPSV. Of patients who screened positive for IPSV, 60.0% had one or
more trauma-associated comorbidity compared to 15.1% of patients who screened
negative (p < 0.001). CONCLUSION: More than one in nine trauma patients is at
risk of IPSV, regardless of gender or mechanism of injury. IPSV may be a risk
factor for other trauma-associated comorbidities. LEVEL OF EVIDENCE:
Prognostic/Epidemiologic, level II; Care Management, level III.
PMID- 28426561
TI - Unfractionated heparin versus low-molecular-weight heparin for venous
thromboembolism prophylaxis in trauma.
AB - BACKGROUND: Venous thromboembolism (VTE) is a common complication in trauma
patients. Pharmacologic prophylaxis is utilized in trauma patients to reduce
their risk of a VTE event. The Eastern Association for the Surgery of Trauma
guidelines recommend use of low-molecular-weight heparin (LMWH) as the preferred
agent in these patients. However, there is literature suggesting that
unfractionated heparin (UFH) is an acceptable, and less costly, alternative VTE
prophylaxis agent with equivalent efficacy in trauma patients. We examined data
from the Michigan Trauma Quality Improvement Program to perform a comparative
effectiveness study of UFH versus LMWH on outcomes for trauma patients. METHODS:
We conducted an analysis of the Michigan Trauma Quality Improvement Program data
from January 2012 to December 2014. The data set contains information on date,
time, and drug type of the first dose of VTE prophylaxis. Thirty-seven thousand
eight hundred sixty-eight patients from 23 hospitals were present with an Injury
Severity Score of 5 or greater and hospitalization for more than 24 hours.
Patients were excluded if they died within 24 hours or received no pharmacologic
VTE prophylaxis or agents other than UFH or LMWH while admitted to the hospital.
We compared patients receiving LMWH to those receiving UFH. Outcomes assessed
were VTE event, pulmonary embolism, deep vein thrombosis, and mortality during
hospitalization. We used a generalized estimating equation approach to fit
population-averaged logistic regression models with the type of first dose of VTE
prophylaxis as the independent variable. Unfractionated heparin was considered
the reference value. Timing of the first dose of VTE prophylaxis was entered into
the model in addition to standard covariates. Odds ratios were generated for each
of the dependent variables of interest. RESULTS: The analysis cohort consisted of
18,010 patients. Patients administered LMWH had a decreased risk of mortality
(odds ratio, 0.64; confidence interval, 0.49-0.83), VTE (odds ratio, 0.67;
confidence interval, 0.53-0.84), pulmonary embolism (odds ratio, 0.53; confidence
interval, 0.35-0.79), and deep vein thrombosis (odds ratio, 0.73; confidence
interval, 0.57-0.95) when compared with UFH following risk adjustment and
accounting for hospital effect. The reduced risk of a VTE event for patients
receiving LMWH was most pronounced for patients in the lower injury-severity
categories. CONCLUSIONS: In our examination of VTE prophylaxis drug
effectiveness, LMWH was found to be superior to UFH in reducing the incidence of
mortality and VTE events among trauma patients. Therefore, LMWH should be the
preferred VTE prophylaxis agent for use in hospitalized trauma patients. LEVEL OF
EVIDENCE: Therapeutic, level III.
PMID- 28426562
TI - Asymptomatic cervical spine fractures: Current guidelines can fail older
patients.
AB - BACKGROUND: Older adults represent a growing proportion of trauma patients
treated in the United States, and cervical spine (c-spine) fracture is an injury
that is increasingly common in this population. Neck pain is a major component of
current clinical clearance guidelines, but some older adults with c-spine
fractures report no neck pain after injury. The objective of this study was to
investigate the frequency at which c-spine fractures were unassociated with neck
pain in an aging population. METHODS: A retrospective review was performed for
patients 55 years or older with a c-spine fracture during a 4-year study period.
All patients had a Glasgow Coma Scale score of 15 and were considered
asymptomatic if they did not complain of neck pain on initial presentation,
denied tenderness to palpation of the c-spine on examination, and were without
neurologic deficit. Differences between groups were assessed with Kruskal-Wallis
and chi tests. RESULTS: Of 173 patients with c-spine fractures, 36 (21%) were
asymptomatic and reported no neck pain on presentation or on examination. The
group without neck pain had higher median injury severity scores (15 vs 10; p <
0.001), were more likely to have another injured body region (69% vs 42%; p =
0.004), and had longer hospitalization (7 vs 5 days; p = 0.008) than patients
with neck pain. Twenty-two percent of the symptomatic group and 19% of the
asymptomatic group required halo, fusion, or other surgical intervention.
DISCUSSION: Study results indicate that one fifth of patients with a c-spine
fracture reported no pain on initial presentation and denied tenderness to
palpation on examination. The presence or absence of pain may be an unreliable
indicator of c-spine fracture in an aging population. When used in conjunction
with existing clearance guidelines, denial of pain may lead to missed injury. We
recommend liberal c-spine imaging for older trauma patients with significant
mechanism of trauma. LEVEL OF EVIDENCE: Therapeutic study, level III.
PMID- 28426563
TI - Routine inclusion of long-term functional and patient-reported outcomes into
trauma registries: The FORTE project.
AB - BACKGROUND: The National Academies of Sciences, Engineering, and Medicine
(formerly the Institute of Medicine) recently recommended inclusion of
postdischarge health-related quality of life (HRQoL) and patient-reported
outcomes (PROs) metrics to benchmark the quality of trauma care. Currently, these
measures are not routinely collected at most trauma centers. We sought to
determine the feasibility and value of adding such long-term outcome measures to
trauma registries. METHODS: As part of the FORTE (Functional Outcomes and
Recovery after Trauma Emergencies) project, we included patients with an Injury
Severity Score of 9 or greater, admitted to the Brigham and Women's Hospital in
Boston, MA, who were identified retrospectively using the institutional trauma
registry and contacted 6 or 12 months after injury to participate in a telephone
survey evaluating HRQoL (Short Form 12 [SF-12]), PROs (Trauma Quality of Life),
posttraumatic stress disorder, return to work, residential status, and health
care utilization. RESULTS: Data were collected for 171 of 394 eligible patients:
85/189 (45%) at 6 months and 86/205 (42%) at 12 months; 25%/29% (6/12 months)
patients could not be contacted, 15%/16% (6/12 months) declined to participate,
and 15%/13% (6/12 months) were interested in participating at another time but
were not reached again. Approximately 20% patients screened positive for
posttraumatic stress disorder, and half had not yet returned to work. There were
significant reductions in SF-12 physical composite scores relative to population
norms (mean, 50 [SD, 10]) at 6 months (mean, 44; 95% confidence interval [CI], 41
47) and 12 months (45; 95% CI, 42-47); no difference was noted in the SF-12
mental composite scores (6 months: 51 [95% CI, 48-54]; 12 months: 50 [95% CI, 46
53]). CONCLUSIONS: Trauma patients reported considerable impairment 6 and 12
months after injury. Routine collection of PROs and HRQoL provides important data
regarding trauma outcomes beyond mortality and will enable the development of
quality improvement metrics that better reflect patients' postinjury experiences.
Improved and alternate methods for collection of these data need to be developed
to enhance response rates before widespread adoption across trauma centers in the
United States. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level II;
Therapeutic, level III.
PMID- 28426564
TI - Report on NPUAP Session: Untangling the Terminology of Unavoidable Pressure
Injuries, Terminal Ulcers, and Skin Failure.
PMID- 28426565
TI - Unavoidable Pressure Injuries, Terminal Ulceration, and Skin Failure: In Search
of a Unifying Classification System.
PMID- 28426567
TI - How Will CMS Edit Therapy Services to Reflect Coding Changes?
PMID- 28426568
TI - Looking Beyond the Cell in Cellulitis.
AB - BACKGROUND: Patients with erythematous skin are likely to receive a diagnosis of
cellulitis; however, the accuracy of this diagnosis is approximately only 33%.
The diagnosis of cellulitis should be made only after a thorough evaluation of
all possible differential diagnoses. Cellulitis may be a primary process
(superficial spreading infective process involving only the epidermis and dermis)
versus a secondary (reactive) process incited by a subcutaneous process, such as
an abscess, tenosynovitis, necrotizing fasciitis, and osteomyelitis. CASE
PRESENTATION: A 50-year-old man was admitted to a general hospital with the
diagnosis of cellulitis. He was initially treated with systemic antibiotics
without improvement. Following consultation with a wound management physician,
the patient received a diagnosis of a pretibial abscess and was treated with
surgical evacuation and postoperative systemic antibiotic therapy guided by
tissue cultures. A postoperative wound was successfully treated with inelastic
compression therapy. CONCLUSIONS: This case demonstrates the potential for
misdiagnosis when evaluating erythematous skin. Furthermore, concluding that the
erythema is due to a primary cellulitis may result in monotherapy with systemic
antimicrobial agents. In such cases, making a correct diagnosis through a
skillful and complete physical examination of the patient, coupled with
appropriate investigations, will lead to the best possible outcome. A
comprehensive treatment approach may include systemic antimicrobials, as well as
surgical options and compression therapy.
PMID- 28426569
TI - Salve and Burdock: A Safe, Effective Amish Remedy for Treatment of Traumatic
Wounds?
AB - BACKGROUND: Amish patients show a demonstrated preference for traditional, herbal
remedies over modern medical interventions such as skin grafting. One such remedy
is a mixture of Burn & Wound Ointment (B & W Ointment; Holistic Acres, LLC;
Newcomerstown, Ohio) and steeped burdock leaves. Although both have demonstrated
some antimicrobial and wound healing properties, burdock and/or the combination
of B & W Ointment and burdock has never been studied to determine its purported
ability to reduce pain, prevent infection, and accelerate wound healing. METHODS:
A retrospective chart review was performed on 6 Amish patients treated with salve
and burdock leaves instead of skin grafting following complex traumatic wounds to
determine whether the traditional treatment incurred any patient harm. RESULTS:
The time of wound epithelialization and healing complications were noted, among
other data points. Time to full epithelialization ranged from 1 to 7 months. Time
to full wound healing was proportional to wound size. CONCLUSIONS: Although the
treatment presented here is unconventional, it did not cause harm to the patients
studied.
PMID- 28426570
TI - Susceptibility of Trichopyton mentagrophytes to Visible Light Wavelengths.
AB - OBJECTIVE: To determine whether a blue light (405 nm) could inhibit the growth of
Trichopyton mentagrophytes without using a photosensitizing material as part of
the treatment protocol. DESIGN: Basic physiologic randomized trial using
laboratory specimens (T mentagrophytes). INTERVENTIONS/METHODS: Plated on a
growth medium, T mentagrophytes were exposed to 3 to 5 administrations of blue
light at 20 J/cm over 28 hours. Following 7 days of incubation, colony-forming
units were counted and compared with nonirradiated controls. RESULTS: The study
found 3, 4, and 5 administrations of blue light produced significant inhibition
of T mentagrophytes (P < .05); 4 and 5 applications produced the greatest
inhibition of growth (84.7% and 93.6% kill rates, respectively). CONCLUSIONS: The
application of 405-nm light at a dose of 20 J/cm is an effective in vitro
inhibitor of T mentagrophytes. To give results similar to those seen when a
photosensitizing material is included, 3 to 5 applications of this wavelength and
dose condition delivered over 28 hours is likely needed.
PMID- 28426571
TI - Growth Differentiation Factor 5 Accelerates Wound Closure and Improves Skin
Quality During Repair of Full-Thickness Skin Defects.
AB - BACKGROUND: A fast and stable wound closure is important, especially for extended
and unstable wounds found after burn injuries. Growth can regulate a variety of
cellular processes, including those involved in wound healing. Growth
differentiation factor 5 (GDF-5) can accelerate fibroblast cell migration, cell
proliferation, and collagen synthesis, which are essential for wound healing.
Nevertheless, no standardized evaluation of the effect of GDF-5 on the healing of
full-thickness wounds has been published to date. METHODS: Five full-thickness
skin defects were created on the backs of 6 minipigs. Three wounds were treated
with GDF-5 in different concentrations with the help of a gelatin-collagen
carrier, and 2 wounds served as control group. The first was treated with the
gelatin carrier and an Opsite film (Smith & Nephew, Fort Worth, Texas), and the
other was treated solely with an Opsite film that was placed above all wounds and
renewed every second day. RESULTS: Growth differentiation factor 5 accelerates
wound closure (10.91 [SD, 0.99] days) compared with treatment with the carrier
alone (11.3 [SD, 1.49] days) and control wounds (13.3 [SD, 0.94] days). Epidermal
cell count of wounds treated with GDF-5 revealed a higher number of cells
compared with the control group. In addition, mean epidermal thickness was
significantly increased in GDF-5-treated wounds compared with the control wounds.
CONCLUSIONS: Because of its ability to improve skin quality, GDF-5 should be
considered when developing composite biomaterials for wound healing.
PMID- 28426572
TI - Nonhealing Ulcers in Patients with Tophaceous Gout: A Systematic Review.
AB - GENERAL PURPOSE: To provide information from a review of the literature about
chronic ulcers associated with tophaceous gout. TARGET AUDIENCE: This continuing
education activity is intended for physicians, physician assistants, nurse
practitioners, and nurses with an interest in skin and wound care. LEARNING
OBJECTIVES/OUTCOMES: After participating in this educational activity, the
participant should be better able to:1. Identify the pathophysiology of
tophaceous gout, its presentation, phases, and common comorbidities.2. Evaluate
the findings in this review regarding effectiveness of interventions for chronic
tophaceous ulcers. ABSTRACT: OBJECTIVE: Treating chronic ulcers associated with
tophaceous gout is an uncommon but important clinical challenge. However,
treatments vary greatly from topical therapies, to debridements, to free flap
wound coverage. To the authors' knowledge, this is the first study to assemble
and compare these different approaches in order to guide effective treatment.
DATA SOURCES: An electronic search of MEDLINE (PubMed) was conducted. Search
terms included (gout and ulcer) not "peptic ulcer," and (gout, chronic wound) or
(gout, nonhealing wound). STUDY SELECTION: Studies that discussed the
presentation, characterization, or treatment of gout-associated wounds were
included. The literature search yielded 9 case reports and case series; there
were no randomized controlled studies or reviews. DATA EXTRACTION: Patient and
wound characteristics, treatment approaches, and outcomes were noted. DATA
SYNTHESIS: The 82% of 22 patients were male, aged 36 to 95 years. Three patients
had not been previously diagnosed with gout, whereas others had received a
diagnosis 2 to 35 years prior to presentation with an ulcer. Many patients had
comorbidities including diabetes and peripheral vascular disease. Most of the 43
total ulcers occurred on the feet. Treatments included topical 3% citric acid in
petroleum jelly, allogeneic culture dermal substitute, silver-containing dressing
and heterologous lyophilized collagen, debridements, and free flap coverage.
CONCLUSIONS: Chronic tophaceous wounds are a worldwide problem. Although
physicians report some successes with different treatments, controlled studies
are needed to determine the most effective approach and to identify risk factors
and preventive strategies.
PMID- 28426573
TI - Quality Payment Program: Advancing Care Information Performance Category: Part 1.
PMID- 28426574
TI - Nonhealing Ulcers in Patients with Tophaceous Gout: A Systematic Review.
PMID- 28426575
TI - Tipping the Scales for Cancer Surgery Outcomes: Anesthetic Influences on Cancer
Progression.
PMID- 28426576
TI - Personalized Intrathecal Drug Delivery: Models, Targets, and Approaches.
PMID- 28426577
TI - Can the Perioperative Anesthesia Care of Patients With Cancer Affect Their Long
term Oncological Outcomes?
PMID- 28426578
TI - Plasma Transfusion as Bleeding Prophylaxis in the Critically Ill.
PMID- 28426579
TI - The PLAIN Truth: Caring for the Amish: What Every Anesthesiologist Should Know.
PMID- 28426580
TI - Neuraxial Labor Analgesia: Does It Influence the Outcomes of Labor?
PMID- 28426581
TI - Anesthesiology and New Models of Perioperative Care: What Will Help Move the
Needle?
PMID- 28426582
TI - Women, Minorities, and Leadership in Anesthesiology: Take the Pledge.
PMID- 28426583
TI - The Law of Unintended Consequences Can Never Be Repealed: The Hazards of Random
Urine Drug Screening of Anesthesia Providers.
PMID- 28426584
TI - Neuromuscular Monitoring as the Art of Probability.
PMID- 28426585
TI - Modeling Spinal Intrathecal Drug Distribution: The Challenge of Defining and
Predicting Cerebrospinal Fluid Dynamics.
PMID- 28426586
TI - Predictive Modeling of Massive Transfusion Requirements During Liver
Transplantation and Its Potential to Reduce Utilization of Blood Bank Resources.
AB - BACKGROUND: Patients undergoing liver transplantation frequently but
inconsistently require massive blood transfusion. The ability to predict massive
transfusion (MT) could reduce the impact on blood bank resources through
customization of the blood order schedule. Current predictive models of MT for
blood product utilization during liver transplantation are not generally
applicable to individual institutions owing to variability in patient population,
intraoperative management, and definitions of MT. Moreover, existing models may
be limited by not incorporating cirrhosis stage or thromboelastography (TEG)
parameters. METHODS: This retrospective cohort study included all patients who
underwent deceased-donor liver transplantation at the Johns Hopkins Hospital
between 2010 and 2014. We defined MT as intraoperative transfusion of > 10 units
of packed red blood cells (pRBCs) and developed a multivariable predictive model
of MT that incorporated cirrhosis stage and TEG parameters. The accuracy of the
model was assessed with the goodness-of-fit test, receiver operating
characteristic analysis, and bootstrap resampling. The distribution of correct
patient classification was then determined as we varied the model threshold for
classifying MT. Finally, the potential impact of these predictions on blood bank
resources was examined. RESULTS: Two hundred three patients were included in the
study. Sixty (29.6%) patients met the definition for MT and received a median
(interquartile range) of 19.0 (14.0-27.0) pRBC units intraoperatively compared
with 4.0 units (1.0-6.0) for those who did not satisfy the criterion for MT. The
multivariable model for predicting MT included Model for End-stage Liver Disease
score, whether simultaneous liver and kidney transplant was performed, cirrhosis
stage, hemoglobin concentration, platelet concentration, and TEG R interval and
angle. This model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit
test P = .45) and good discrimination (c statistic: 0.835; 95% confidence
interval, 0.781-0.888). A probability cutoff threshold of 0.25 was found to
misclassify only 4 of 100 patients as unlikely to experience MT, with the
majority such misclassifications within 4 units of the working definition for MT.
For this threshold, a preoperative blood ordering schedule that allocated 6 units
of pRBCs for those unlikely to experience MT and 15 for those who were likely to
experience MT would prevent unnecessary crossmatching of 338 units/100
transplants. CONCLUSIONS: When clinical and laboratory parameters are included, a
model predicting intraoperative MT in patients undergoing liver transplantation
is sufficiently accurate that its predictions could guide the blood order
schedule for individual patients based on institutional data, thereby reducing
the impact on blood bank resources. Ongoing evaluation of model accuracy and
transfusion practices is required to ensure continuing performance of the
predictive model.
PMID- 28426587
TI - Reduced Blood Viscosity Plays Minor Role in Regional Blood Flow Increases During
Acute Normovolemic Hemodilution.
PMID- 28426588
TI - In Response.
PMID- 28426590
TI - In Response.
PMID- 28426589
TI - Open Access, Crowd-Sourced Repository of Anesthesia Information (Wiki-Anesthesia)
as Antidote to Inaccurate Internet-Based Resources.
PMID- 28426591
TI - Overregulation Revisited.
PMID- 28426592
TI - In Response.
PMID- 28426593
TI - Showing and Telling! Screencasts for Enhanced Feedback on Student Writing.
PMID- 28426594
TI - Enhancing Cross-Curricular Connectedness and Collaboration From Associate Degree
to Clinical Doctorate.
PMID- 28426595
TI - Creative Strategies for Teaching Millennial Nursing Students.
PMID- 28426596
TI - Worldwide Abortion Rates and Access to Contraception.
PMID- 28426597
TI - Accommodating Immigrant Women's Preferences for Female Health Care Providers.
AB - OBJECTIVE: To investigate obstetricians' perspectives of the importance, effect,
and challenges of providing intrapartum care to immigrant women who request a
female obstetrician. METHODS: A focused ethnography was conducted at a large
teaching hospital, which serves a high proportion of immigrant clientele
(predominantly North or East African, Middle Eastern, and South Asian) in
Edmonton, Alberta, Canada. Data collection comprised single, semistructured
interviews with a purposive sample of 20 obstetric health care providers (10
resident and 10 staff obstetricians). Interviews were audio-recorded and
transcribed verbatim. Data were managed with Quirkos and analyzed using thematic
analysis. RESULTS: A total of 13 female and seven male physicians were
interviewed. Physicians recognized the validity of immigrant women's preference
and requests for female health care providers and expressed sympathy for them.
However, they were also resistant and expressed several concerns about
accommodating these requests, including fear of perpetuating and exacerbating
gender inequalities in medicine, the extent to which patient decision-making was
coercion-free, the ability of the health system to meet the demands, and
implications for training and quality of care. CONCLUSION: Although physicians
were sympathetic to immigrant women's requests for female obstetricians, they
placed greater value on maintaining gender equity both within the medical
profession and in wider society and resisted accommodating gender-of-health-care
provider requests. Our qualitative study suggests a need for greater research to
inform policy that meets the professional and personal values of both physicians
and patients.
PMID- 28426598
TI - Listen to Women.
PMID- 28426599
TI - Blood Loss as a Function of Body Surface Area: Redefining Parameters of Obstetric
Blood Loss.
PMID- 28426600
TI - In Reply.
PMID- 28426601
TI - Interpregnancy Interval After Termination of Pregnancy and the Risks of Adverse
Outcomes in Subsequent Birth.
PMID- 28426602
TI - In Reply.
PMID- 28426603
TI - Operationalizing 17alpha-Hydroxyprogesterone Caproate to Prevent Recurrent
Preterm Birth: Definitions, Barriers, and Next Steps.
PMID- 28426604
TI - In Reply.
PMID- 28426605
TI - Maternal Deaths From Suicide and Overdose in Colorado, 2004-2012.
PMID- 28426606
TI - Preeclampsia and Long-term Risk of Maternal Retinal Disorders.
PMID- 28426607
TI - In Reply.
PMID- 28426608
TI - Attempted and Successful Vacuum-Assisted Vaginal Delivery by Prepregnancy Body
Mass Index.
PMID- 28426613
TI - Practice Bulletin No. 178 Summary: Shoulder Dystocia.
PMID- 28426614
TI - Committee Opinion No. 698 Summary: Hormone Therapy in Primary Ovarian
Insufficiency.
AB - Primary ovarian insufficiency describes a spectrum of declining ovarian function
and reduced fecundity due to a premature decrease in initial follicle number, an
increase in follicle destruction, or poor follicular response to gonadotropins.
The sequelae of primary ovarian insufficiency include vasomotor symptoms,
urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and
increased all-cause mortality. In women with primary ovarian insufficiency,
systemic hormone therapy (HT) is an effective approach to treat the symptoms of
hypoestrogenism and mitigate long-term health risks if there are no
contraindications to treatment. Hormone therapy is indicated to reduce the risk
of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve
the quality of life of women with primary ovarian insufficiency. Although
exogenous estrogen replacement is recommended for women with primary ovarian
insufficiency, data comparing various hormonal regimens for disease prevention,
symptom amelioration, and safety are lacking in this population. As a first-line
approach, HT (either orally or transdermally) that achieves replacement levels of
estrogen is recommended. Combined hormonal contraceptives prevent ovulation and
pregnancy more reliably than HT; despite only modest odds of spontaneous
pregnancy in women with primary ovarian insufficiency, this is a critical
consideration for those who deem pregnancy prevention a priority. Treatment for
all women with primary ovarian insufficiency should continue until the average
age of natural menopause is reached (age 50-51 years). Finally, considering the
challenges that adolescents and young women may face in coping with the physical,
reproductive, and social effects of primary ovarian insufficiency, comprehensive
longitudinal management of this condition is essential.
PMID- 28426615
TI - Committee Opinion No. 699: Adolescent Pregnancy, Contraception, and Sexual
Activity.
AB - In 2015, the birth rate among U.S. adolescents and young adults (aged 15-19
years) reached a historic low at 22.3 per 1,000 women. Despite positive trends,
the United States continues to have the highest adolescent pregnancy rate among
industrialized countries with data. Racial and ethnic disparities in adolescent
pregnancy rates continue to exist, as do state-based differences in pregnancy,
birth, and abortion rates. The American College of Obstetricians and
Gynecologists supports access for adolescents to all contraceptive methods
approved by the U.S. Food and Drug Administration. In the absence of
contraindications, patient choice should be the principal factor in prescribing
one method of contraception over another. Dual method use-the use of condoms in
combination with more effective contraceptive methods to protect against sexually
transmitted infections and unwanted pregnancy-is the ideal contraceptive practice
for adolescents. Just as adolescents should have access to the full range of
contraceptives, including long-acting reversible contraceptive methods, they
should be able to decline and discontinue any method on their own, without
barriers. A reproductive justice framework for contraceptive counseling and
access is essential to providing equitable health care, accessing and having
coverage for contraceptive methods, and resisting potential coercion by health
care providers. Successful programs that resulted in measurable changes in
adolescent contraceptive practices and sexual behavior have been described, but
not implemented uniformly nor supported by policy improvements. More research is
needed to determine which programs are most effective and which programs do not
work. Continued efforts are integral to further advance positive trends.
PMID- 28426616
TI - Committee Opinion No. 700 Summary: Methods for Estimating the Due Date.
AB - Accurate dating of pregnancy is important to improve outcomes and is a research
and public health imperative. As soon as data from the last menstrual period, the
first accurate ultrasound examination, or both are obtained, the gestational age
and the estimated due date (EDD) should be determined, discussed with the
patient, and documented clearly in the medical record. Subsequent changes to the
EDD should be reserved for rare circumstances, discussed with the patient, and
documented clearly in the medical record. A pregnancy without an ultrasound
examination that confirms or revises the EDD before 22 0/7 weeks of gestational
age should be considered suboptimally dated. When determined from the methods
outlined in this document for estimating the due date, gestational age at
delivery represents the best obstetric estimate for the purpose of clinical care
and should be recorded on the birth certificate. For the purposes of research and
surveillance, the best obstetric estimate, rather than estimates based on the
last menstrual period alone, should be used as the measure for gestational age.
PMID- 28426617
TI - Clinical Updates in Women's Health Care Summary: Arrhythmias: Primary and
Preventive Care Review.
AB - Obstetrician-gynecologists often are the sole providers of health care to female
patients. Because cardiovascular disease is the leading cause of death in women
in the United States, obstetrician- gynecologists must be aware of the risk
factors, symptoms, and signs of cardiovascular disease and arrhythmia.
Furthermore, they must be prepared to identify and treat common types of
arrhythmia in this population and refer patients to cardiology for specialized
care. Understanding the role of pregnancy among women with arrhythmia is
critically important to optimize both maternal and fetal outcomes. This monograph
discusses the cardiac conduction system and addresses the assessment, diagnosis,
and treatment of both pregnant and nonpregnant patients with heart rhythm
disorders.
PMID- 28426618
TI - Practice Bulletin No 178: Shoulder Dystocia.
PMID- 28426619
TI - Committee Opinion No. 698: Hormone Therapy in Primary Ovarian Insufficiency.
AB - Primary ovarian insufficiency describes a spectrum of declining ovarian function
and reduced fecundity due to a premature decrease in initial follicle number, an
increase in follicle destruction, or poor follicular response to gonadotropins.
The sequelae of primary ovarian insufficiency include vasomotor symptoms,
urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and
increased all-cause mortality. In women with primary ovarian insufficiency,
systemic hormone therapy (HT) is an effective approach to treat the symptoms of
hypoestrogenism and mitigate long-term health risks if there are no
contraindications to treatment. Hormone therapy is indicated to reduce the risk
of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve
the quality of life of women with primary ovarian insufficiency. Although
exogenous estrogen replacement is recommended for women with primary ovarian
insufficiency, data comparing various hormonal regimens for disease prevention,
symptom amelioration, and safety are lacking in this population. As a first-line
approach, HT (either orally or transdermally) that achieves replacement levels of
estrogen is recommended. Combined hormonal contraceptives prevent ovulation and
pregnancy more reliably than HT; despite only modest odds of spontaneous
pregnancy in women with primary ovarian insufficiency, this is a critical
consideration for those who deem pregnancy prevention a priority. Treatment for
all women with primary ovarian insufficiency should continue until the average
age of natural menopause is reached (age 50-51 years). Finally, considering the
challenges that adolescents and young women may face in coping with the physical,
reproductive, and social effects of primary ovarian insufficiency, comprehensive
longitudinal management of this condition is essential.
PMID- 28426620
TI - Committee Opinion No 699: Adolescent Pregnancy, Contraception, and Sexual
Activity.
AB - In 2015, the birth rate among U.S. adolescents and young adults (aged 15-19
years) reached a historic low at 22.3 per 1,000 women. Despite positive trends,
the United States continues to have the highest adolescent pregnancy rate among
industrialized countries with data. Racial and ethnic disparities in adolescent
pregnancy rates continue to exist, as do state-based differences in pregnancy,
birth, and abortion rates. The American College of Obstetricians and
Gynecologists supports access for adolescents to all contraceptive methods
approved by the U.S. Food and Drug Administration. In the absence of
contraindications, patient choice should be the principal factor in prescribing
one method of contraception over another. Dual method use-the use of condoms in
combination with more effective contraceptive methods to protect against sexually
transmitted infections and unwanted pregnancy-is the ideal contraceptive practice
for adolescents. Just as adolescents should have access to the full range of
contraceptives, including long-acting reversible contraceptive methods, they
should be able to decline and discontinue any method on their own, without
barriers. A reproductive justice framework for contraceptive counseling and
access is essential to providing equitable health care, accessing and having
coverage for contraceptive methods, and resisting potential coercion by health
care providers. Successful programs that resulted in measurable changes in
adolescent contraceptive practices and sexual behavior have been described, but
not implemented uniformly nor supported by policy improvements. More research is
needed to determine which programs are most effective and which programs do not
work. Continued efforts are integral to further advance positive trends.
PMID- 28426621
TI - Committee Opinion No 700: Methods for Estimating the Due Date.
AB - Accurate dating of pregnancy is important to improve outcomes and is a research
and public health imperative. As soon as data from the last menstrual period, the
first accurate ultrasound examination, or both are obtained, the gestational age
and the estimated due date (EDD) should be determined, discussed with the
patient, and documented clearly in the medical record. Subsequent changes to the
EDD should be reserved for rare circumstances, discussed with the patient, and
documented clearly in the medical record. A pregnancy without an ultrasound
examination that confirms or revises the EDD before 22 0/7 weeks of gestational
age should be considered suboptimally dated. When determined from the methods
outlined in this document for estimating the due date, gestational age at
delivery represents the best obstetric estimate for the purpose of clinical care
and should be recorded on the birth certificate. For the purposes of research and
surveillance, the best obstetric estimate, rather than estimates based on the
last menstrual period alone, should be used as the measure for gestational age.
PMID- 28426622
TI - CHANGES IN CENTRAL CHOROIDAL THICKNESS AFTER TREATMENT OF DIABETIC MACULAR EDEMA
WITH INTRAVITREAL BEVACIZUMAB CORRELATION WITH CENTRAL MACULAR THICKNESS AND BEST
CORRECTED VISUAL ACUITY.
AB - PURPOSE: To assess the effect of intravitreal injection of bevacizumab on central
choroidal thickness (CCT) and its relationship with central macular thickness
(CMT) and best-corrected visual acuity (BCVA) changes in eyes with center
involving diabetic macular edema. METHODS: This prospective interventional case
series included 20 eyes of 20 patients with center-involving diabetic macular
edema naive to treatment. The BCVA assessment, complete eye examination, enhanced
depth optical coherence tomography, and fluorescein angiography were performed at
baseline followed by 3 monthly intravitreal injection of bevacizumab. The treated
eyes underwent BCVA evaluation and enhanced depth optical coherence tomography at
Months 1, 2, 3, and 6 after the first injection. Change of the CCT was the
primary outcome measure. Secondary outcome measures included BCVA and CMT changes
and their relationship with CCT changes. RESULTS: Mean age of patients was 63.1
+/- 8.0 (range, 52-75) years. Mean baseline CCT was 265 +/- 79 MUm, which reduced
to 251 +/- 81 MUm and 232 +/- 82 MUm at Months 3 and 6, respectively (P < 0.001).
Corresponding values for CMT were 470 +/- 107 MUm, 392 +/- 104 MUm, and 324 +/-
122 MUm, respectively (P < 0.001). The BCVA improved from 20/60 at baseline to
20/50 at Month 3 and 20/40 at Month 6 (P = 0.007). Each 1 MUm decrease in CCT was
associated with 2.74 MUm reduction in CMT and 0.1 Early Treatment Diabetic
Retinopathy Study letter score improvement in BCVA (P < 0.001 and P = 0.001,
respectively). CONCLUSION: After treatment of diabetic macular edema with
intravitreal injection of bevacizumab, CCT decreased and this reduction
significantly correlated with CMT reduction and vision improvement.
PMID- 28426623
TI - INTRAVITREAL DEXAMETHASONE IMPLANTATION IN PATIENTS WITH DIFFERENT MORPHOLOGICAL
DIABETIC MACULAR EDEMA HAVING INSUFFICIENT RESPONSE TO RANIBIZUMAB.
AB - PURPOSE: To evaluate the effectiveness of a single intravitreal injection of
dexamethasone implant in resistant diabetic macular edema that have different
morphological types. METHODS: In this retrospective study, 31 patients (35 eyes)
with persistent diabetic macular edema, who underwent a single injection of
dexamethasone implant, were evaluated. Diabetic macular edema was classified into
three types: diffuse retinal thickening (n = 10), cystoid macular edema (n = 13),
and serous retinal detachment (n = 12). Primary outcome measures were best
corrected visual acuity, and central macular thickness. RESULTS: The three
subgroups were similar in terms of age and gender (P > 0.05). Total duration of
diabetes was significantly less in the serous retinal detachment subgroup (P =
0.01). There were no differences in the best corrected visual acuity between the
three subgroups until the sixth month. However, the best corrected visual acuity
was significantly better in the diffuse retinal thickness subgroup at the sixth
month (P = 0.008). Regarding the central macular thickness values, it was
statistically better in serous retinal detachment than in diffuse retinal
thickening and cystoid macular edema subgroups till the sixth month (P = 0.001).
However, at the sixth month, there was not any statistical difference between
subgroups regarding central macular thickness values. Antiglaucomatous agents
were required in 4 (11.4%) patients throughout the study. CONCLUSION: Treatment
algorithms should differ according to the morphology of diabetic macular edema;
however, more data is needed to give specific recommendations.
PMID- 28426624
TI - A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROL PILOT STUDY OF EPLERENONE FOR THE
TREATMENT OF CENTRAL SEROUS CHORIORETINOPATHY (ECSELSIOR).
AB - PURPOSE: To evaluate the safety and effects of oral eplerenone in chronic central
serous chorioretinopathy. METHODS: Prospective, randomized, double-blind, placebo
control study at a tertiary referral academic private practice. For a diagnosis
of chronic central serous chorioretinopathy, patients must have had at least 3
months clinical follow-up demonstrating persistent symptoms, subfoveal fluid on
spectral-domain optical coherence tomography, and <50% reduction in fluid
thickness. Patients were randomized 2:1 (treatment:placebo) to receive eplerenone
(25 mg daily for 1 week, then up to 50 mg daily for 8 weeks) or placebo once
daily. RESULTS: Fifteen patients completed the study. Ten patients (15 eyes) were
randomized into the eplerenone treatment arm, while the remaining 5 patients (6
eyes) received placebo. After 9 weeks of eplerenone therapy, mean logarithm of
the minimal angle of resolution visual acuity improved from 0.394 (Snellen
equivalent: 20/50) to 0.330 (20/43, P = 0.04). In the placebo group, the mean
logarithm of the minimal angle of resolution visual acuity slightly decreased
from 0.313 (20/41) to 0.342 (20/44) during the same period (P = 0.21). With
respect to anatomic changes, mean maximal subretinal fluid height in the
eplerenone group improved from 139.3 MUm at baseline to 51.8 MUm (P = 0.02), mean
subfoveal fluid height improved from 121.4 MUm to 29.4 MUm (P = 0.01), and mean
central subfield thickness improved from 366.2 MUm to 283.7 MUm (P = 0.02). In
comparison with the placebo group, mean maximal subretinal fluid height worsened
from 135.9 MUm to 172.3 MUm (P = 0.32), mean subfoveal fluid height worsened from
92.1 MUm to 134.0 MUm (P = 0.54), and mean central subfield thickness worsened
from 345.0 MUm to 380.0 MUm (P = 0.37). No patients in either group experienced
serious adverse events to result in treatment discontinuation. CONCLUSION: These
findings suggest that oral eplerenone therapy is safe and potentially effective
in the treatment of chronic central serous chorioretinopathy with persistent
subretinal fluid.
PMID- 28426625
TI - Intraoperative Optical Coherence Tomography-Assisted Chorioretinal Biopsy in the
DISCOVER Study.
PMID- 28426626
TI - PARAPAPILLARY GAMMA AND DELTA ZONES IN HIGH MYOPIA.
AB - PURPOSE: To examine parapapillary zones gamma and delta in highly myopic eyes.
METHODS: The retrospective observational study included patients attending the
Tokyo high myopia clinics. Fundus photographs were morphometrically examined.
RESULTS: The study population included 600 eyes (304 individuals) with a mean age
of 62.7 +/- 14.3 years (range: 13-90 years) and mean axial length of 29.6 +/- 2.2
mm (range: 23.2-35.4 mm). In multivariate analysis (regression coefficient
r:0.90), larger horizontal gamma zone diameter was correlated with wider delta
zone diameter (P < 0.001; standardized regression coefficient beta: 0.81), higher
ratio of vertical-to-horizontal disk diameter (P < 0.001; beta: 0.10), shorter
fovea-outer gamma zone border distance (P < 0.001; beta: -0.19), longer disk
fovea distance (P < 0.001; beta: 0.18), and higher count of chorioretinal
atrophic lesions (P < 0.001; beta: 0.07). Longer horizontal delta zone width was
correlated with longer horizontal gamma zone diameter (P < 0.001; beta: 1.00),
longer horizontal disk diameter (P < 0.001; beta: 0.15), shorter disk-fovea
distance (P < 0.001; beta: -0.19), longer fovea-outer gamma zone border distance
(P < 0.001; beta: 0.19), and smaller diameter of the largest chorioretinal lesion
(P = 0.03; beta: -0.04). Longer width of both zones together was associated with
longer horizontal disk diameter (P < 0.001; beta: 0.31), higher ratio of vertical
to-horizontal disk diameter (P = 0.001; beta: 0.18), longer disk-fovea distance
(P < 0.001; beta: 0.19), shorter fovea-outer gamma zone border distance (P <
0.001; beta: -0.18), higher number of chorioretinal lesions (P < 0.001; beta:
0.30), and longer vertical distance between the superior and inferior temporal
arterial arcade (P = 0.001; beta: 0.13). CONCLUSION: Larger gamma and delta zones
were correlated with larger optic disk and more marked vertical optic disk
rotation, longer disk-fovea distance, higher number of chorioretinal lesions, and
longer temporal vascular arcade diameter. Parapapillary gamma and delta zones may
develop before chorioretinal lesions develop and enlarge.
PMID- 28426627
TI - High Visual Acuity Retinal Prosthesis: Understanding Limitations and Advancements
Toward Functional Prosthetic Vision.
PMID- 28426629
TI - Correspondence.
PMID- 28426628
TI - OCULAR HYPERTENSION AND GLAUCOMA FOLLOWING VITRECTOMY: A Systematic Review.
AB - PURPOSE: Pars plana vitrectomy has been reported to increase the risk of ocular
hypertension and open-angle glaucoma. The authors conducted a systematic review
of randomized and nonrandomized studies to compare the incidence of open-angle
glaucoma and ocular hypertension in vitrectomized versus nonvitrectomized eyes.
METHODS: A literature search was performed using MEDLINE and EMBASE until August
2016. Data on ocular hypertension and open-angle glaucoma incidence and mean
intraocular pressure after at least 1 year were pooled using random-effects
metaanalysis models. Because only nonrandomized studies were retrieved, ROBINS-I
tool was used to assess risk of bias in the review. RESULTS: Seven included
studies had a paired design to compare the outcomes of vitrectomized versus
fellow eyes, with mean follow-up of least 12 months. Four studies (851 patients)
provided data on open-angle glaucoma: incidence in vitrectomized versus non
vitrectomized eyes was 7.8% and 4.8%, respectively, yielding a metaanalytic odds
ratio of 1.67 (95% CI: 1.08-2.57). Six studies (1,060 patients) reported on the
occurrence of ocular hypertension, which was 5.8% in vitrectomized eyes versus
3.1% in fellow eyes (odds ratio: 2.03, 95% CI: 0.97-4.22), without significant
differences in the mean postoperative intraocular pressure (mean difference 0.31
mmHg, 95% CI: -0.26 to 0.89). CONCLUSION: Although the review found increased
risk of open-angle glaucoma with pars plana vitrectomy, the studies were
heterogenous or inconsistent regarding ocular hypertension and intraocular
pressure increase. Larger studies should be conducted in homogenous cohorts of
patients undergoing macular surgery, excluding complex conditions such as retinal
detachment or diabetic retinopathy.
PMID- 28426630
TI - OUTER NUCLEAR LAYER THINNING IN PACHYCHOROID PIGMENT EPITHELIOPATHY.
AB - PURPOSE: To compare the average thicknesses of central inner retinal layers in
eyes with pachychoroid pigment epitheliopathy (PPE), with uncomplicated
pachychoroid (UCP), and of healthy subjects. METHODS: Medical records of patients
with PPE and UCP were retrospectively reviewed. Twenty-nine eyes with foveal PPE,
30 eyes with UCP, and 29 eyes of healthy subjects were included. Spectral-domain
optical coherence tomography with enhanced depth imaging was used for all optical
coherence tomography scans. Mean central inner retinal layer thicknesses were
measured in 1-mm-diameter circle with Spectralis automated segmentation software
and compared between groups. RESULTS: The outer nuclear layer (ONL) and the sum
of the outer plexiform layer and ONL were significantly thinner in the PPE group
than the UCP and control groups (ONL: P < 0.001, P < 0.001; outer plexiform layer
+ ONL: P = 0.002, P = 0.002, respectively). There was no significant difference
between groups regarding thickness of the outer plexiform layer and other inner
retinal layers. Eyes with UCP and normal eyes did not differ. CONCLUSION: The ONL
is thinner in eyes with PPE. The degenerative process of pachychoroid spectrum
diseases may begin with retinal pigment epithelium alterations before subretinal
fluid accumulation. The PPE lesions, commonly seen above pachyvessels, may be an
indicator of photoreceptor apoptosis.
PMID- 28426632
TI - Intraoperative Use of Microscope-Integrated Optical Coherence Tomography for
Subretinal Gene Therapy Delivery.
PMID- 28426631
TI - DIRECTIONAL CHANGES IN TISSUE REFLECTIVITY MAY INFLUENCE FLOW DETECTION ON
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: To determine if directional or anatomical changes in tissue reflectivity
of Henle fiber layer (HFL) may influence flow detection on optical coherence
tomography angiography (OCT-A). METHODS: Cross-sectional analysis of consecutive
cases undergoing OCT-A. Directional changes in visualization of HFL were either
produced manually by moving the beam entrance within the pupil or observed
occurring naturally because of tilting of the OCT line-scan within a myopic
staphyloma. Areas of enhanced HFL visualization were identified on cross
sectional and en face structural OCT scans. Visualization of OCT-A flow within
the superficial and the deep capillary plexuses were compared in areas with and
without enhanced HFL reflectivity. RESULTS: Fifteen eyes from 9 patients were
included, with a mean age of 49.6 +/- 17.9 years. On OCT-A, retinal areas with
enhanced HFL reflectivity produced manually or by scan tilting within myopic
staphylomas showed no changes in the superficial capillary plexus flow. However,
deep capillary plexus flow was altered by variable projection of the superficial
flow onto the deeper retinal layers. CONCLUSION: Directional changes in HFL
reflectivity can alter the detection of deep capillary plexus flow imaged with
OCT-A by influencing the projection of superficial flow onto the deeper retinal
layers. We recommend that clinicians minimize scan tilting during scan
acquisition and be aware of this phenomenon in eyes with posterior staphyloma.
PMID- 28426633
TI - Reply.
PMID- 28426636
TI - Use of Mindfulness in Coping With Incivility.
PMID- 28426635
TI - A Life Well Lived: A Tribute to Dr Kathleen T. Heinrich.
PMID- 28426637
TI - Creating Web Sites in Nursing Education.
PMID- 28426638
TI - Decreased Central Nervous System Grey Matter Volume (GMV) in Smokers Affects
Cognitive Abilities: A Systematic Review.
AB - Although cigarette smoking is a leading cause of preventable mortality, tobacco
is consumed by approximately 22% of the adult population worldwide. Smoking is
also a risk factor for cardiovascular disease, affects brain processing, and is a
recognized risk factor for Alzheimer disease (AD). Tobacco toxins (e.g., nicotine
at high levels) inhaled in smoke may cause disorders resulting in preclinical
brain changes. Researchers suggest that there are differences in brain volume
between smokers and non-smokers. This review examines these differences in brain
grey matter volume (GMV). In March/April 2015, MedLine, Embase, and PsycINFO were
searched using the terms: "grey matter" AND "voxel-based" AND "smoking" AND
"cigarette". The 4 studies analyzed found brain GMV decreases in smokers compared
to non-smokers. Furthermore, sex-specific differences were found; while the
thalamus and cerebellum were affected in both sexes, decreased GMV in the
olfactory gyrus was found only in male smokers. Age-group differences were also
found, and these may suggest pre-existing abnormalities that lead to nicotine
dependence in younger individuals. Only 1 study found a positive correlation
between number of pack-years smoked and GMV. Smoking decreases GMV in most brain
areas. This decrease may be responsible for the cognitive impairment and
difficulties with emotional regulation found in smokers compared with non
smokers.
PMID- 28426639
TI - Restaurant Food Allergy Practices - Six Selected Sites, United States, 2014.
AB - Food allergies affect an estimated 15 million persons in the United States (1),
and are responsible for approximately 30,000 emergency department visits and 150
200 deaths each year (2). Nearly half of reported fatal food allergy reactions
over a 13-year period were caused by food from a restaurant or other food service
establishment (3). To ascertain the prevalence of food allergy training, training
topics, and practices related to food allergies, CDC's Environmental Health
Specialists Network (EHS-Net), a collaborative forum of federal agencies and
state and local health departments with six sites, interviewed personnel at 278
restaurants. Fewer than half of the 277 restaurant managers (44.4%), 211 food
workers (40.8%), and 156 servers (33.3%) interviewed reported receiving food
allergy training. Among those who reported receiving training, topics commonly
included the major food allergens and what to do if a customer has a food
allergy. Although most restaurants had ingredient lists for at least some menu
items, few had separate equipment or areas designated for the preparation of
allergen-free food. Restaurants can reduce the risk for allergic reactions among
patrons by providing food allergy training for personnel and ingredient lists for
all menu items and by dedicating equipment and areas specifically for preparing
allergen-free food.
PMID- 28426640
TI - Announcement: Sleep Awareness Week, April 23-29, 2017.
AB - Sleep Awareness Week, the National Sleep Foundation's annual campaign to educate
the public about the importance of sleep in health and safety, will be observed
April 23-29, 2017. The amount of sleep a person needs changes with age. Adults
need >=7 hours each night to promote optimal health and well-being (1); children
and adolescents require even more sleep. Sleep needs decrease from 12-16 hours of
sleep per 24 hours (including naps) for infants aged 4-12 months to 8-10 hours of
sleep for teenagers aged 13-18 years (2). Children who regularly sleep less than
the recommended amount are more likely to have behavior and learning problems,
physical and mental health conditions such as obesity, diabetes, depression, or
injuries (2). A regular bedtime routine can help children get adequate sleep. The
American Academy of Pediatrics provides advice for parents at
https://www.healthychildren.org/English/healthy-living/sleep/. Additional details
about how much sleep is recommended across a lifespan is available at
https://www.cdc.gov/sleep/about_sleep/how_much_sleep.html.
PMID- 28426641
TI - Notes from the Field: Powassan Virus Disease in an Infant - Connecticut, 2016.
PMID- 28426642
TI - QuickStats: Number of Deaths from 10 Leading Causes,* by Sex - National Vital
Statistics System, United States, 2015.
AB - In 2015, a total of 1,339,226 deaths among females and 1,373,404 deaths among
males occurred. Heart disease and cancer were the top two causes of death for
both females and males; other leading causes varied in rank by sex. The 10
leading causes of death accounted for approximately three-quarters of all deaths.
PMID- 28426643
TI - Incidence and Trends of Infections with Pathogens Transmitted Commonly Through
Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on
Surveillance - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites,
2013-2016.
AB - Foodborne diseases represent a substantial public health concern in the United
States. CDC's Foodborne Diseases Active Surveillance Network (FoodNet) monitors
cases reported from 10 U.S. sites* of laboratory-diagnosed infections caused by
nine enteric pathogens commonly transmitted through food. This report describes
preliminary surveillance data for 2016 on the nine pathogens and changes in
incidences compared with 2013-2015. In 2016, FoodNet identified 24,029
infections, 5,512 hospitalizations, and 98 deaths caused by these pathogens. The
use of culture-independent diagnostic tests (CIDTs) by clinical laboratories to
detect enteric pathogens has been steadily increasing since FoodNet began
surveying clinical laboratories in 2010 (1). CIDTs complicate the interpretation
of FoodNet surveillance data because pathogen detection could be affected by
changes in health care provider behaviors or laboratory testing practices (2).
Health care providers might be more likely to order CIDTs because these tests are
quicker and easier to use than traditional culture methods, a circumstance that
could increase pathogen detection (3). Similarly, pathogen detection could also
be increasing as clinical laboratories adopt DNA-based syndromic panels, which
include pathogens not often included in routine stool culture (4,5). In addition,
CIDTs do not yield isolates, which public health officials rely on to distinguish
pathogen subtypes, determine antimicrobial resistance, monitor trends, and detect
outbreaks. To obtain isolates for infections identified by CIDTs, laboratories
must perform reflex culture?; if clinical laboratories do not, the burden of
culturing falls to state public health laboratories, which might not be able to
absorb that burden as the adoption of these tests increases (2). Strategies are
needed to preserve access to bacterial isolates for further characterization and
to determine the effect of changing trends in testing practices on surveillance.
PMID- 28426644
TI - Notes from the Field: Varicella Fatality on a Cargo Vessel - Puerto Rico, 2015.
PMID- 28426645
TI - Announcement: World Malaria Day - April 25, 2017.
AB - World Malaria Day is commemorated each year on April 25, the date in 2000 when
leaders of 44 African nations met in Abuja, Nigeria, and committed their
countries to reducing the number of malaria-related deaths. Approximately 90% of
all malaria deaths occur in Africa (1). During the last 15 years, donors have
collectively supported the procurement and distribution of billions of
insecticide-treated bed nets and courses of artemisinin-based combination therapy
globally. These improvements in malaria control are estimated to have saved an
estimated 6.8 million lives, mostly among children aged <5 years. From 2010 to
2015, the World Health Organization (WHO) reported that the estimated number of
malaria deaths worldwide declined by approximately 60%, including a 69% decline
among children aged <5 years (1). This year, as in 2016, the theme of World
Malaria Day is "End Malaria for Good," reflecting the increased interest in and
commitment to eliminating malaria.
PMID- 28426646
TI - Community Mitigation Guidelines to Prevent Pandemic Influenza - United States,
2017.
AB - When a novel influenza A virus with pandemic potential emerges, nonpharmaceutical
interventions (NPIs) often are the most readily available interventions to help
slow transmission of the virus in communities, which is especially important
before a pandemic vaccine becomes widely available. NPIs, also known as community
mitigation measures, are actions that persons and communities can take to help
slow the spread of respiratory virus infections, including seasonal and pandemic
influenza viruses.These guidelines replace the 2007 Interim Pre-pandemic Planning
Guidance: Community Strategy for Pandemic Influenza Mitigation in the United
States - Early, Targeted, Layered Use of Nonpharmaceutical Interventions
(https://stacks.cdc.gov/view/cdc/11425). Several elements remain unchanged from
the 2007 guidance, which described recommended NPIs and the supporting rationale
and key concepts for the use of these interventions during influenza pandemics.
NPIs can be phased in, or layered, on the basis of pandemic severity and local
transmission patterns over time. Categories of NPIs include personal protective
measures for everyday use (e.g., voluntary home isolation of ill persons,
respiratory etiquette, and hand hygiene); personal protective measures reserved
for influenza pandemics (e.g., voluntary home quarantine of exposed household
members and use of face masks in community settings when ill); community measures
aimed at increasing social distancing (e.g., school closures and dismissals,
social distancing in workplaces, and postponing or cancelling mass gatherings);
and environmental measures (e.g., routine cleaning of frequently touched
surfaces).Several new elements have been incorporated into the 2017 guidelines.
First, to support updated recommendations on the use of NPIs, the latest
scientific evidence available since the influenza A (H1N1)pdm09 pandemic has been
added. Second, a summary of lessons learned from the 2009 H1N1 pandemic response
is presented to underscore the importance of broad and flexible prepandemic
planning. Third, a new section on community engagement has been included to
highlight that the timely and effective use of NPIs depends on community
acceptance and active participation. Fourth, to provide new or updated pandemic
assessment and planning tools, the novel influenza virus pandemic intervals tool,
the Influenza Risk Assessment Tool, the Pandemic Severity Assessment Framework,
and a set of prepandemic planning scenarios are described. Finally, to facilitate
implementation of the updated guidelines and to assist states and localities with
prepandemic planning and decision-making, this report links to six supplemental
prepandemic NPI planning guides for different community settings that are
available online (https://www.cdc.gov/nonpharmaceutical-interventions).
PMID- 28426647
TI - Association of prenatal urinary phthalate metabolite concentrations and childhood
BMI and obesity.
AB - BackgroundAlthough experiments in animals suggest that phthalates may have
obesogenic effects, studies on prenatal exposure in children show inconsistent
results.MethodsWe measured urinary concentrations of 11 phthalate metabolites
collected twice during pregnancy from mothers participating in the Center for the
Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study
(N=345). Height, weight, waist circumference, and percent body fat were assessed
in their children between 5 and 12 years of age. We used generalized estimating
equations to examine associations at each age and tested for interaction by
sex.ResultsMetabolites of diethyl phthalate (DEP), di-n-butyl phthalate (DBP),
butyl benzyl phthalate, and di(2-ethylhexyl) phthalate (DEHP) were positively
associated with BMI z-score, waist circumference z-score, and percent body fat at
multiple ages. At age 12, we observed increased odds of being overweight/obese
with each doubling of prenatal concentrations of DEP (odds ratio=1.3; 95%
confidence intervals: 1.1, 1.4), DBP (1.2; 1.0, 1.4), and DEHP (1.3; 1.0, 1.6)
metabolites. Results were similar in boys and girls except for DBP metabolites
and the non-specific metabolite mono-(3-carboxypropyl) phthalate, which showed
positive associations only in boys.ConclusionIn utero exposure to certain
phthalates is associated with increased BMI and risk for overweight/obesity in
childhood.
PMID- 28426648
TI - Pregnancy swimming causes short- and long-term neuroprotection against hypoxia
ischemia in very immature rats.
AB - BackgroundHypoxia-ischemia (HI) is a major cause of neurological damage in
preterm newborn. Swimming during pregnancy alters the offspring's brain
development. We tested the effects of swimming during pregnancy in the very
immature rat brain.MethodsFemale Wistar rats (n=12) were assigned to the
sedentary (SE, n=6) or the swimming (SW, n=6) group. From gestational day 0 (GD0)
to GD21 the rats in the SW group were made to swim for 20 min/day. HI on
postnatal day (PND) 3 rats caused sensorimotor and cognitive impairments. Animals
were distributed into SE sham (SESH), sedentary HIP3 (SEHI), swimming sham
(SWSH), and swimming HIP3 (SWHI) groups. At PND4 and PND5, Na+/K+-ATPase activity
and brain-derived neurotrophic factor (BDNF) levels were assessed. During
lactation and adulthood, neurological reflexes, sensorimotor, anxiety-related,
and cognitive evaluations were made, followed by histological assessment at
PND60.ResultsAt early stages, swimming caused an increase in hippocampal BDNF
levels and in the maintenance of Na+/K+-ATPase function in the SWHI group. The
SWHI group showed smaller lesions and the preservation of white matter tracts.
SEHI animals showed a delay in reflex maturation, which was reverted in the SWHI
group. HIP3 induced spatial memory deficits and hypomyelination in SEHI rats,
which was reverted in the SWHI group.ConclusionSwimming during pregnancy
neuroprotected the brains against HI in very immature neonatal rats.
PMID- 28426649
TI - The importance of appropriate initial bacterial colonization of the intestine in
newborn, child, and adult health.
AB - The fetus does not reside in a sterile intrauterine environment and is exposed to
commensal bacteria from the maternal gut/blood stream that cross the placenta and
enter the amniotic fluid. This intestinal exposure to colonizing bacteria
continues at birth and during the first year of life and has a profound influence
on lifelong health. Why is this important? Intestinal crosstalk with colonizing
bacteria in the developing intestine affects the infant's adaptation to
extrauterine life (immune homeostasis) and provides protection against disease
expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing
intestinal bacteria are critical to the normal development of host defense.
Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section
delivery, use of perinatal antibiotics, or premature delivery may adversely
affect the gut development of host defense and predispose to inflammation rather
than to homeostasis, leading to increased susceptibility to disease later in
life. Babies born by cesarean section have a higher incidence of allergy, type 1
diabetes, and obesity. Infants given repeated antibiotic regimens during the
first year of life are more likely to have asthma as adolescents. This research
breakthrough helps to explain the shift in disease paradigms from infections to
immune-mediated in children from developed countries. This review will develop
this research breakthrough.
PMID- 28426650
TI - Neural injury markers in intrauterine growth restriction and their relation to
perinatal outcomes.
AB - BACKGROUNDThe aims of this study were to (i) compare the concentrations of two
neural injury markers, S100B protein and neuron-specific enolase (NSE), in
intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate
growth-for-gestational-age (AGA), and (ii) investigate potential relationships
between concentrations of these markers, Doppler abnormalities, and adverse
perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative,
prospective study among Spanish Maternal and Child Health Network (Retic SAMID)
hospitals. At inclusion, biometry for estimated fetal weight and feto-placental
Doppler were measured. At the time of delivery, maternal venous blood and fetal
umbilical arterial blood samples were collected. S100B and NSE concentrations
were determined from these samples.RESULTSIn total, 254 pregnancies were
included. Among these, 147 were classified as IUGR and 107 as AGA. There were no
differences between the groups in S100B concentrations. However, levels of NSE in
maternal and umbilical cord serum differed significantly between these groups
(2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR
(P<0.05), respectively). No differences were observed in these neurological
markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough
some variations exist in these neurological markers, they did not correlate with
perinatal or neonatal complications.
PMID- 28426651
TI - Association of candidate gene polymorphisms with clinical subtypes of preterm
birth in a Latin American population.
AB - BackgroundPreterm birth (PTB) is the leading cause of neonatal mortality and
morbidity. PTB is often classified according to clinical presentation as follows:
idiopathic (PTB-I), preterm premature rupture of membranes (PTB-PPROM), and
medically induced (PTB-M). The aim of this study was to evaluate the associations
between specific candidate genes and clinical subtypes of PTB.MethodsTwenty-four
single-nucleotide polymorphisms (SNPs) were genotyped in 18 candidate genes in
709 infant triads. Of them, 243 were PTB-I, 256 were PTB-PPROM, and 210 were PTB
M. These data were analyzed with a Family-Based Association.ResultsPTB was
nominally associated with rs2272365 in PON1, rs883319 in KCNN3, rs4458044 in
CRHR1, and rs610277 in F3. Regarding clinical subtypes analysis, three SNPs were
associated with PTB-I (rs2272365 in PON1, rs10178458 in COL4A3, and rs4458044 in
CRHR1), rs610277 in F3 was associated with PTB-PPROM, and rs883319 in KCNN3 and
rs610277 in F3 were associated with PTB-M.ConclusionOur study identified
polymorphisms potentially associated with specific clinical subtypes of PTB in
this Latin American population. These results could suggest a specific role of
such genes in the mechanisms involved in each clinical subtype. Further studies
are required to confirm our results and to determine the role of these genes in
the pathophysiology of clinical subtypes.
PMID- 28426653
TI - The evolving schistosomiasis agenda 2007-2017-Why we are moving beyond morbidity
control toward elimination of transmission.
PMID- 28426652
TI - Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction
(PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF
kappaB Ligand (RANKL).
AB - We present an in silico drug discovery pipeline developed and applied for the
identification and virtual screening of small-molecule Protein-Protein
Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through
the trimerization interface. The cheminformatics part of the pipeline was
developed by combining structure-based with ligand-based modeling using the
largest available set of known TNF inhibitors in the literature (2481 small
molecules). To facilitate virtual screening, the consensus predictive model was
made freely available at: http://enalos.insilicotox.com/TNFPubChem/. We thus
generated a priority list of nine small molecules as candidates for direct TNF
function inhibition. In vitro evaluation of these compounds led to the selection
of two small molecules that act as potent direct inhibitors of TNF function, with
IC50 values comparable to those of a previously-described direct inhibitor
(SPD304), but with significantly reduced toxicity. These molecules were also
identified as RANKL inhibitors and validated in vitro with respect to this second
functionality. Direct binding of the two compounds was confirmed both for TNF and
RANKL, as well as their ability to inhibit the biologically-active trimer forms.
Molecular dynamics calculations were also carried out for the two small molecules
in each protein to offer additional insight into the interactions that govern TNF
and RANKL complex formation. To our knowledge, these compounds, namely T8 and
T23, constitute the second and third published examples of dual small-molecule
direct function inhibitors of TNF and RANKL, and could serve as lead compounds
for the development of novel treatments for inflammatory and autoimmune diseases.
PMID- 28426654
TI - Mycetoma: A global medical and socio-economic dilemma.
PMID- 28426655
TI - Glycosome biogenesis in trypanosomes and the de novo dilemma.
AB - Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative
agents of lethal diseases threatening millions of people around the world. These
organisms compartmentalize glycolysis in essential, specialized peroxisomes
called glycosomes. Peroxisome proliferation can occur through growth and division
of existing organelles and de novo biogenesis from the endoplasmic reticulum. The
level that each pathway contributes is debated. Current evidence supports the
concerted contribution of both mechanisms in an equilibrium that can vary
depending on environmental conditions and metabolic requirements of the cell.
Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis
and matrix protein import, have been identified in T. brucei. Based on these
findings, it is widely accepted that glycosomes proliferate through growth and
division of existing organelles; however, to our knowledge, a de novo mechanism
of biogenesis has not been directly demonstrated. Here, we review recent findings
that provide support for the existence of an endoplasmic reticulum (ER)-derived
de novo pathway of glycosome biogenesis in T. brucei. Two studies recently
identified PEX13.1, a peroxin involved in matrix protein import, in the ER of
procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been
found in the ER of cells undergoing de novo biogenesis of peroxisomes. In
addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are
important for de novo biogenesis in other eukaryotes. Because glycosomes are
rapidly remodeled via autophagy during life cycle differentiation, de novo
biogenesis could provide a method of restoring glycosome populations following
turnover. Together, the findings we summarize provide support for the hypothesis
that glycosome proliferation occurs through growth and division of pre-existing
organelles and de novo biogenesis of new organelles from the ER and that the
level each mechanism contributes is influenced by glucose availability.
PMID- 28426657
TI - Cystic and alveolar echinococcosis: Successes and continuing challenges.
PMID- 28426656
TI - The role of 'omics' in the quest to eliminate human filariasis.
PMID- 28426658
TI - The PLOS Neglected Tropical Diseases decade.
PMID- 28426659
TI - Three distinct mechanisms of long-distance modulation of gene expression in
yeast.
AB - Recent Hi-C measurements have revealed numerous intra- and inter-chromosomal
interactions in various eukaryotic cells. To what extent these interactions
regulate gene expression is not clear. This question is particularly intriguing
in budding yeast because it has extensive long-distance chromosomal interactions
but few cases of gene regulation over-a-distance. Here, we developed a medium
throughput assay to screen for functional long-distance interactions that affect
the average expression level of a reporter gene as well as its cell-to-cell
variability (noise). We ectopically inserted an insulated MET3 promoter (MET3pr)
flanked by ~1kb invariable sequences into thousands of genomic loci, allowing it
to make contacts with different parts of the genome, and assayed the MET3pr
activity in single cells. Changes of MET3pr activity in this case necessarily
involve mechanisms that function over a distance. MET3pr has similar activities
at most locations. However, at some locations, they deviate from the norm and
exhibit three distinct patterns including low expression / high noise, low
expression / low noise, and high expression / low noise. We provided evidence
that these three patterns of MET3pr expression are caused by Sir2-mediated
silencing, transcriptional interference, and 3D clustering. The clustering also
occurs in the native genome and enhances the transcription of endogenous Met4
targeted genes. Overall, our results demonstrate that a small fraction of long
distance chromosomal interactions can affect gene expression in yeast.
PMID- 28426661
TI - Parasite genomics-Time to think bigger.
PMID- 28426660
TI - Exhaustive search of linear information encoding protein-peptide recognition.
AB - High-throughput in vitro methods have been extensively applied to identify linear
information that encodes peptide recognition. However, these methods are limited
in number of peptides, sequence variation, and length of peptides that can be
explored, and often produce solutions that are not found in the cell. Despite the
large number of methods developed to attempt addressing these issues, the
exhaustive search of linear information encoding protein-peptide recognition has
been so far physically unfeasible. Here, we describe a strategy, called DALEL,
for the exhaustive search of linear sequence information encoded in proteins that
bind to a common partner. We applied DALEL to explore binding specificity of SH3
domains in the budding yeast Saccharomyces cerevisiae. Using only the polypeptide
sequences of SH3 domain binding proteins, we succeeded in identifying the
majority of known SH3 binding sites previously discovered either in vitro or in
vivo. Moreover, we discovered a number of sites with both non-canonical sequences
and distinct properties that may serve ancillary roles in peptide recognition. We
compared DALEL to a variety of state-of-the-art algorithms in the blind
identification of known binding sites of the human Grb2 SH3 domain. We also
benchmarked DALEL on curated biological motifs derived from the ELM database to
evaluate the effect of increasing/decreasing the enrichment of the motifs. Our
strategy can be applied in conjunction with experimental data of proteins
interacting with a common partner to identify binding sites among them. Yet, our
strategy can also be applied to any group of proteins of interest to identify
enriched linear motifs or to exhaustively explore the space of linear information
encoded in a polypeptide sequence. Finally, we have developed a webserver located
at http://michnick.bcm.umontreal.ca/dalel, offering user-friendly interface and
providing different scenarios utilizing DALEL.
PMID- 28426662
TI - PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical
disease control and elimination ... More or less.
AB - This year PLOS Neglected Tropical Diseases (PLOS NTDs) celebrates its tenth
anniversary following the publication of the first issue in 2007 [1]. When PLOS
NTDs was founded, the framework of the neglected tropical diseases (NTDs) as an
alternative to "other diseases" (as they were then referred to in the Millennium
Development Goals) was just getting started-especially for Africa [2, 3]. In the
decade since, PLOS NTDs has overseen enormous successes in NTD control and
elimination. Here, we want to briefly review the ten year progress made towards
the control or elimination of the diseases now identified by the WHO as NTDs.
Many of the details are highlighted in PLOS NTDs papers cited here, but the
summary information is based on the recently released Global Burden of Disease
(GBD) Study 2015 (also launched with Gates Foundation support) that summarized
past-decade changes in disease prevalence, mortality, or disability rates (from
the years 2005 to 2015) [4-6], as well as the GBD Study 2013 that summarizes
disease prevalence changes over a longer time horizon from 1990 to 2013 [7].
PMID- 28426663
TI - Guinea worm eradication: Progress and challenges- should we beware of the dog?
PMID- 28426664
TI - Taenia solium cysticercosis and taeniosis: Achievements from the past 10 years
and the way forward.
PMID- 28426666
TI - Neglected tropical diseases: A DFID perspective.
PMID- 28426665
TI - Oncodomains: A protein domain-centric framework for analyzing rare variants in
tumor samples.
AB - The fight against cancer is hindered by its highly heterogeneous nature. Genome
wide sequencing studies have shown that individual malignancies contain many
mutations that range from those commonly found in tumor genomes to rare somatic
variants present only in a small fraction of lesions. Such rare somatic variants
dominate the landscape of genomic mutations in cancer, yet efforts to correlate
somatic mutations found in one or few individuals with functional roles have been
largely unsuccessful. Traditional methods for identifying somatic variants that
drive cancer are 'gene-centric' in that they consider only somatic variants
within a particular gene and make no comparison to other similar genes in the
same family that may play a similar role in cancer. In this work, we present
oncodomain hotspots, a new 'domain-centric' method for identifying clusters of
somatic mutations across entire gene families using protein domain models. Our
analysis confirms that our approach creates a framework for leveraging structural
and functional information encapsulated by protein domains into the analysis of
somatic variants in cancer, enabling the assessment of even rare somatic variants
by comparison to similar genes. Our results reveal a vast landscape of somatic
variants that act at the level of domain families altering pathways known to be
involved with cancer such as protein phosphorylation, signaling, gene regulation,
and cell metabolism. Due to oncodomain hotspots' unique ability to assess rare
variants, we expect our method to become an important tool for the analysis of
sequenced tumor genomes, complementing existing methods.
PMID- 28426668
TI - Neglected tropical diseases: A proxy for equitable development and shared
prosperity.
PMID- 28426667
TI - Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a
zebrafish model of spinal muscular atrophy.
AB - Degeneration and loss of lower motor neurons is the major pathological hallmark
of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously
expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved,
feature of SMA is that not all motor neurons are equally affected, with some
populations displaying a robust resistance to the disease. Here, we demonstrate
that selective vulnerability of distinct motor neuron pools arises from
fundamental modifications to their basal molecular profiles. Comparative gene
expression profiling of motor neurons innervating the extensor digitorum longus
(disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis
anterior (vulnerable) muscles in mice revealed that disease susceptibility
correlates strongly with a modified bioenergetic profile. Targeting of identified
bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon
defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein,
phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron
vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic
the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or
treatment with terazosin (an FDA-approved small molecule that binds and activates
Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global
bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor
neuron phenotypes in vivo.
PMID- 28426669
TI - A dynamic genetic-hormonal regulatory network model explains multiple cellular
behaviors of the root apical meristem of Arabidopsis thaliana.
AB - The study of the concerted action of hormones and transcription factors is
fundamental to understand cell differentiation and pattern formation during organ
development. The root apical meristem of Arabidopsis thaliana is a useful model
to address this. It has a stem cell niche near its tip conformed of a quiescent
organizer and stem or initial cells around it, then a proliferation domain
followed by a transition domain, where cells diminish division rate before
transiting to the elongation zone; here, cells grow anisotropically prior to
their final differentiation towards the plant base. A minimal model of the gene
regulatory network that underlies cell-fate specification and patterning at the
root stem cell niche was proposed before. In this study, we update and couple
such network with both the auxin and cytokinin hormone signaling pathways to
address how they collectively give rise to attractors that correspond to the
genetic and hormonal activity profiles that are characteristic of different cell
types along A. thaliana root apical meristem. We used a Boolean model of the
genetic-hormonal regulatory network to integrate known and predicted regulatory
interactions into alternative models. Our analyses show that, after adding some
putative missing interactions, the model includes the necessary and sufficient
components and regulatory interactions to recover attractors characteristic of
the root cell types, including the auxin and cytokinin activity profiles that
correlate with different cellular behaviors along the root apical meristem.
Furthermore, the model predicts the existence of activity configurations that
could correspond to the transition domain. The model also provides a possible
explanation for apparently paradoxical cellular behaviors in the root meristem.
For example, how auxin may induce and at the same time inhibit WOX5 expression.
According to the model proposed here the hormonal regulation of WOX5 might depend
on the cell type. Our results illustrate how non-linear multi-stable qualitative
network models can aid at understanding how transcriptional regulators and
hormonal signaling pathways are dynamically coupled and may underlie both the
acquisition of cell fate and the emergence of hormonal activity profiles that
arise during complex organ development.
PMID- 28426670
TI - Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1)
show modestly enhanced alcohol preference and consumption.
AB - We recently characterized S426A/S430A mutant mice expressing a desensitization
resistant form of the CB1 receptor. These mice display an enhanced response to
endocannabinoids and ?9-THC. In this study, S426A/S430A mutants were used as a
novel model to test whether ethanol consumption, morphine dependence, and reward
for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1.
Using an unlimited-access, two-bottle choice, voluntary drinking paradigm,
S426A/S430A mutants exhibit modestly increased intake and preference for low (6%)
but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice
show similar taste preference for sucrose and quinine, exhibit normal sensitivity
to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol
concentrations following administration of ethanol. S426A/S430A mutants develop
robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg),
and cocaine (10 mg/kg), demonstrating that drug reward is not changed in
S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid
dependent S426A/S430A mutant mice. Although ethanol consumption is modestly
changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to
ethanol and morphine are normal in this model.
PMID- 28426671
TI - Effect of mitochondrially targeted carboxy proxyl nitroxide on Akt-mediated
survival in Daudi cells: Significance of a dual mode of action.
AB - Vicious cycles of mutations and reactive oxygen species (ROS) generation
contribute to cancer progression. The use of antioxidants to inhibit ROS
generation promotes cytostasis by affecting the mutation cycle and ROS-dependent
survival signaling. However, cancer cells select mutations to elevate ROS albeit
maintaining mitochondrial hyperpolarization (Deltapsim), even under hypoxia. From
this perspective, the use of drugs that disrupt both ROS generation and Deltapsim
is a viable anticancer strategy. Hence, we studied the effects of mitochondrially
targeted carboxy proxyl nitroxide (Mito-CP) and a control ten carbon TPP moiety
(Dec-TPP+) in the human Burkitt lymphoma cell line (Daudi) and normal peripheral
blood mononuclear cells under hypoxia and normoxia. We found preferential
localization, Deltapsim and adenosine triphosphate loss, and significant
cytotoxicity by Mito-CP in Daudi cells alone. Interestingly, ROS levels were
decreased and maintained in hypoxic and normoxic cancer cells, respectively, by
Mito-CP but not Dec-TPP+, therefore preventing any adaptive signaling. Moreover,
dual effects on mitochondrial bioenergetics and ROS by Mito-CP curtailed the
cancer survival via Akt inhibition, AMPK-HIF-1alpha activation and promoted
apoptosis via increased BCL2-associated X protein and poly (ADP-ribose)
polymerase expression. This dual mode of action by Mito-CP provides a better
explanation of the application of antioxidants with specific relevance to
cancerous transformation and adaptations in the Daudi cell line.
PMID- 28426672
TI - How to determine if a model is right for neglected tropical disease decision
making.
AB - Mathematical and computational modeling can transform decision making for
neglected tropical diseases (NTDs) if the right model is used for the right
question. Modeling can help better understand and address the complex systems
involved in making decisions for NTD prevention and control. However, all models,
modelers, and modeling are not the same. Thus, decision makers need to better
understand if a particular model actually fits their needs. Here are a series of
questions that a decision maker can ask when determining whether a model is right
for him or her.
PMID- 28426673
TI - Lymph node volume predicts survival but not nodal clearance in Stage IIIA-IIIB
NSCLC.
AB - BACKGROUND: Locally advanced non-small cell lung cancer (LA-NSCLC) patients have
poorer survival and local control with mediastinal node (N2) tumor involvement at
resection. Earlier assessment of nodal burden could inform clinical decision
making prior to surgery. This study evaluated the association between clinical
outcomes and lymph node volume before and after neoadjuvant therapy. MATERIALS
AND METHODS: CT imaging of patients with operable LA-NSCLC treated with
chemoradiation and surgical resection was assessed. Clinically involved lymph
node stations were identified by FDG-PET or mediastinoscopy. Locoregional
recurrence (LRR), distant metastasis (DM), progression free survival (PFS) and
overall survival (OS) were analyzed by the Kaplan Meier method, concordance index
and Cox regression. RESULTS: 73 patients with Stage IIIA-IIIB NSCLC treated with
neoadjuvant chemoradiation and surgical resection were identified. The median RT
dose was 54 Gy and all patients received concurrent chemotherapy. Involved lymph
node volume was significantly associated with LRR and OS but not DM on univariate
analysis. Additionally, lymph node volume greater than 10.6 cm3 after the
completion of preoperative chemoradiation was associated with increased LRR
(p<0.001) and decreased OS (p = 0.04). There was no association between nodal
volumes and nodal clearance. CONCLUSION: For patients with LA-NSCLC, large volume
nodal disease post-chemoradiation is associated with increased risk of
locoregional recurrence and decreased survival. Nodal volume can thus be used to
further stratify patients within the heterogeneous Stage IIIA-IIIB population and
potentially guide clinical decision-making.
PMID- 28426674
TI - Tribological investigations of the load, temperature, and time dependence of wear
in sliding contact.
AB - An effort was made to study and characterize the evolution of transient
tribological wear in the presence of sliding contact. Sliding contact is often
characterized experimentally via the standard ASTM D4172 four-ball test, and
these tests were conducted for varying times ranging from 10 seconds to 1 hour,
as well as at varying temperatures and loads. A numerical model was developed to
simulate the evolution of wear in the elastohydrodynamic regime. This model uses
the results of a Monte Carlo study to develop novel empirical equations for wear
rate as a function of asperity height and lubricant thickness; these equations
closely represented the experimental data and successfully modeled the sliding
contact.
PMID- 28426675
TI - Indicators of suboptimal biologic therapy over time in patients with ulcerative
colitis and Crohn's disease in the United States.
AB - This study assessed the occurrence of indicators for suboptimal biologic therapy
among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the
United States (US). Data from a large US claims database (2005-2013) were used to
retrospectively identify patients with diagnosed with either UC or CD who were
new biologic users. Indicators of suboptimal biologic therapy included: dose
escalation during the maintenance phase, discontinuation of the initial biologic,
switch to another biologic within 90 days following the last day of supply of the
initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD
related surgery, UC- or CD-related urgent care, and development of fistula (for
CD only). Kaplan-Meier analyses were used. A total of 1,699 UC and 4,569 CD
patients were included. Among UC patients, 51.1% and 90.9% experienced >=1
indicator of suboptimal biologic therapy within 6 months and 36 months of
biologic therapy initiation, respectively. Among CD patients, 54.3% and 91.4%
experienced >=1 indicator of suboptimal biologic therapy within 6 and 36 months
of biologic therapy initiation, respectively. For both UC and CD patients, the
most frequent indicators of suboptimal biologic therapy were discontinuation,
dose escalation and augmentation. In conclusion, this study found that the
occurrence of suboptimal biologic therapy is common among patients with UC and
CD, with approximately 90% of patients experiencing at least one indicator of
suboptimal biologic therapy within 36 months of biologic treatment initiation.
PMID- 28426676
TI - Economic injury levels for Asian citrus psyllid control in process oranges from
mature trees with high incidence of huanglongbing.
AB - The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the key pest of
citrus wherever it occurs due to its role as vector of huanglongbing (HLB) also
known as citrus greening disease. Insecticidal vector control is considered to be
the primary strategy for HLB management and is typically intense owing to the
severity of this disease. While this approach slows spread and also decreases
severity of HLB once the disease is established, economic viability of
increasingly frequent sprays is uncertain. Lacking until now were studies
evaluating the optimum frequency of insecticide applications to mature trees
during the growing season under conditions of high HLB incidence. We related
different degrees of insecticide control with ACP abundance and ultimately, with
HLB-associated yield losses in two four-year replicated experiments conducted in
commercial groves of mature orange trees under high HLB incidence. Decisions on
insecticide applications directed at ACP were made by project managers and
confined to designated plots according to experimental design. All operational
costs as well as production benefits were taken into account for economic
analysis. The relationship between management costs, ACP abundance and HLB
associated economic losses based on current prices for process oranges was used
to determine the optimum frequency and timing for insecticide applications during
the growing season. Trees under the most intensive insecticidal control harbored
fewest ACP resulting in greatest yields. The relationship between vector
densities and yield loss was significant but differed between the two test
orchards, possibly due to varying initial HLB infection levels, ACP populations
or cultivar response. Based on these relationships, treatment thresholds during
the growing season were obtained as a function of application costs, juice market
prices and ACP densities. A conservative threshold for mature trees with high
incidence of HLB would help maintain economic viability by reducing excessive
insecticide sprays, thereby leaving more room for non-aggressive management tools
such as biological control.
PMID- 28426677
TI - Information ranks highest: Expectations of female adolescents with a rare genital
malformation towards health care services.
AB - BACKGROUND: Access to highly specialized health care services and support to meet
the patient's specific needs is critical for health outcome, especially during
age-related transitions within the health care system such as with adolescents
entering adult medicine. Being affected by an orphan disease complicates the
situation in several important respects. Long distances to dedicated institutions
and scarcity of knowledge, even among medical doctors, may present major
obstacles for proper access to health care services and health chances. This
study is part of the BMBF funded TransCareO project examining in a mixed-method
design health care provisional deficits, preferences, and barriers in health care
access as perceived by female adolescents affected by the Mayer-Rokitansky-Kuster
Hauser syndrome (MRKHS), a rare (orphan) genital malformation. METHODS: Prior to
a communicative validation workshop, critical elements of MRKHS related care and
support (items) were identified in interviews with MRKHS patients. During the
subsequent workshop, 87 persons involved in health care and support for MRKHS
were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1,
strongly disagree) as to 1) the elements' potential importance (i.e., health care
expected to be "best practice", or priority) and 2) the presently experienced
care. A gap score between the two was computed highlighting fields of action.
Items were arranged into ten separate questionnaires representing domains of care
and support (e.g., online-portal, patient participation). Within each domain,
several items addressed various aspects of "information" and "access". Here, we
present the outcome of items' evaluation by patients (attended, NPAT = 35;
respondents, NRESP = 19). RESULTS: Highest priority scores occurred for domains
"Online-Portal", "Patient participation", and "Tailored informational offers",
characterizing them as extremely important for the perception as best practice.
Highest gap scores yielded domains "Tailored informational offers", reflecting
perceived lack of disease-related information for affected persons, medical
experts, and health insurance companies, "Online-Portal" (with limited
information available on specialist clinics and specialized doctors), and
regarding insufficient support offers (e.g., in school and occupational
settings). Conversely, lowest gap scores were found with group offers for MRKHS
patients ("Transition programs") and MRKHS self-help days ("Patient
participation"), suggesting satisfaction or good solutions in place. DISCUSSION:
The importance assigned to disease-related information indicates that
informational deficits are perceived by patients as barriers, hindering proper
access to health care, especially in an orphan disease. Access to health-related
information plays a role for all persons seeking help and care. However, the
overwhelmingly high scores attributed to these elements in the context of an
orphan disease reveal that here improved information policies are crucial,
demanding for institutionalized solutions supported by the health care system.
IMPLICATIONS FOR PRACTICE: The disparity between experience of care and
attribution as best practice detected describes areas of action in all domains
involved, highlighting information related fields. New concepts and structures
for health care in orphan diseases could draw upon these patient-oriented results
a) regarding orphan-disease specific elements demanding institutionalized
reimbursement, b) essential elements for center care and corresponding networks,
and c) elements reflecting patients' participation in the conception of centers
for rare diseases.
PMID- 28426678
TI - Nutrition education improves dietary diversity of children 6-23 months at
community-level: Results from a cluster randomized controlled trial in Malawi.
AB - BACKGROUND: Low dietary quality and quantity and inappropriate feeding practices
can cause undernutrition. Poor nutritional status in early childhood is
associated with growth faltering. The objective of the study was to assess the
potential of community-based nutrition education to improve height-for-age z
scores in children 6-23 months of age. METHODS AND FINDINGS: We carried out a
cluster-randomized-controlled trial to assess the effectiveness of nutrition
education. A total of 24 Extension Planning Area Sections served as clusters. The
selection criteria were: the position of the extension officer was staffed and
the sections had been selected by the project for activities in its first project
year. The sections were randomized into intervention and control restricted on
mean height for age Z-score using baseline information. In the intervention area,
food security activities and community-based nutrition education was implemented.
The control area received food security activities only. At baseline (2011) and
endline (2014), caregivers with a child below two years of age were enrolled.
Data assessment included anthropometric measurements, interviews on socio
economic status, dietary intake and feeding practices. A difference-in
differences estimator was used to calculate intervention effects. A positive
impact on child dietary diversity was observed (B (SE) = 0.39 (0.15), p = 0.01;
95%CI 0.09-0.68). There was a non-significant positive intervention effect on
mean height-for-age z-scores (B (SE) = 0.17 (0.12), p = 0.15; 95%CI -0.06-0.41).
LIMITATIONS: The 24h dietary recalls used to measure dietary diversity did not
consider quantities of consumed foods. Unrecorded poor quality of consumed foods
might have masked a potential benefit of increased child dietary diversity on
growth. CONCLUSIONS: Participatory community-based nutrition education for
caregivers improved child dietary diversity even in a food insecure area.
Nutrition education should be part of programs in food insecure settings aiming
at ameliorating food insecurity among communities.
PMID- 28426679
TI - Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using
attractive toxic sugar baits (ATSB).
AB - INTRODUCTION: Attractive Toxic Sugar Baits (ATSB) is a new vector control method
that meets Integrated Vector Management (IVM) goals. In an experimental design,
this study aimed to determine effects of ATSB on control of Phlebotomus papatasi,
as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province,
center of Iran. METHODS: In a cross-sectional design, boric acid was mixed with
brown sugar solution and tested as toxic baits for P. papatasi. Two methods were
utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs;
and (b) setting ATSB-treated barrier fences in front of colonies at 500 m
distance from the houses in outskirts of villages. In order to examine the
residual efficacy rate of ATSB-treated barrier fences, the bioassay test was
used. Density of P. papatasi sandflies was measured using sticky and light traps
biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used.
Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi
population. Besides that, ATSB spraying on plants led to more than 5 times
reduction in P. papatasi population. CONCLUSIONS: Comparing the incidence of
leishmaniasis in treated villages before and after the study showed that the
incidence was statistically reduced. Therefore, ATSB is an effective method to
control vectors and prevent leishmaniasis.
PMID- 28426680
TI - Echocardiographic findings in infants with presumed congenital Zika syndrome:
Retrospective case series study.
AB - OBJECTIVE: To report the echocardiographic evaluation of 103 infants with
presumed congenital Zika syndrome. METHODS: An observational retrospective study
was performed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP),
Recife, Brazil. 103 infants with presumed congenital Zika syndrome. All infants
had microcephaly and head computed tomography findings compatible with congenital
Zika syndrome. Zika IgM antibody was detected in cerebrospinal fluid samples of
23 infants. In 80 infants, the test was not performed because it was not
available at that time. All infants had negative serology for HIV, syphilis,
rubella, cytomegalovirus and toxoplasmosis. A complete transthoracic two
dimensional, M-mode, continuous wave and pulsed wave Doppler and color Doppler
echocardiographic (PHILIPS HD11XE or HD15) examination was performed on all
infants. RESULTS: 14/103 (13.5%) echocardiograms were compatible with congenital
heart disease: 5 with an ostium secundum atrial septal defect, 8 had a
hemodynamically insignificant small apical muscular ventricular septal defect and
one infant with dyspnea had a large membranous ventricular septal defect. The
echocardiograms considered normal included 45 infants with a persistent foramen
ovale and 16 with a minimum patent ductus arteriosus. CONCLUSIONS: Preliminarily
this study suggests that congenital Zika syndrome may be associated with an
increase prevalence of congenital heart disease. However the types of defects
noted were septal defects, a proportion of which would not be hemodynamically
significant.
PMID- 28426681
TI - Preventing, treating, and predicting barbering: A fundamental role for biomarkers
of oxidative stress in a mouse model of Trichotillomania.
AB - Barbering, where a "barber" mouse plucks hair from its cagemates or itself, is
both a spontaneously occurring abnormal behavior in mice and a well validated
model of Trichotillomania (TTM). N-Acetylcysteine, (NAC) a cysteine derived food
additive, is remarkably effective in treating TTM patients, but its mechanism of
action is unknown. Reactive Oxygen Species (ROS), also known as free radicals,
form as a natural byproduct of the normal metabolism of oxygen. Under normal
circumstances, cells are able to defend themselves against ROS damage with
antioxidant pathways. NAC is the precursor to the main antioxidant produced to
defend the brain. Therefore, we hypothesized that barbering is a disease of
oxidative stress, whereby ROS and/or a failure of antioxidant defenses leads to
neuronal damage that induces barbering in susceptible animals. We tested this
hypothesis in 32 female C57BL/6J mice by treating half with 1g/kg BW/day of NAC
in their diet, and testing for protection against developing barbering behavior
and curing of barbering behavior, and simultaneously testing for a panel of
biomarkers of oxidative stress. NAC reduced the chance that mice would be
barbers, and this effect did not differ between healthy (i.e. prevention) and
affected animals (i.e. cure). Barbering animals had elevated urinary antioxidant
capacity, indicative of oxidative stress, at all timepoints. Additionally, after
treatment the risk of barbering increased with decreasing hydroxy-2'
deoxyguanosine (8-OHdG) levels, and with increasing glutathione (GSH) and
oxidized glutathione (GSSG) levels, further indicating that barbering mice were
under oxidative stress regardless of treatment with NAC. We did not find
compelling evidence that urinary total antioxidant capacity, or urinary 8-OHdG,
could predict response to NAC treatment. We conclude that NAC is effective in
preventing and/or curing barbering at least in part by promoting GSH synthesis,
thereby preventing oxidative damage.
PMID- 28426682
TI - Automated measurement of cattle surface temperature and its correlation with
rectal temperature.
AB - The body temperature of cattle varies regularly with both the reproductive cycle
and disease status. Establishing an automatic method for monitoring body
temperature may facilitate better management of reproduction and disease control
in cattle. Here, we developed an Automatic Measurement System for Cattle's
Surface Temperature (AMSCST) to measure the temperature of metatarsus by
attaching a special shell designed to fit the anatomy of cattle's hind leg. Using
AMSCST, the surface temperature (ST) on the metatarsus of the hind leg was
successively measured during 24 hours a day with an interval of one hour in three
tested seasons. Based on ST and rectal temperature (RT) detected by AMSCST and
mercury thermometer, respectively, a linear mixed model was established,
regarding both the time point and seasonal factors as the fixed effects. Unary
linear correlation and Bland-Altman analysis results indicated that the
temperatures measured by AMSCST were closely correlated to those measured by
mercury thermometer (R2 = 0.998), suggesting that the AMSCST is an accurate and
reliable way to detect cattle's body temperature. Statistical analysis showed
that the differences of STs among the three seasons, or among the different time
points were significant (P<0.05), and the differences of RTs among the different
time points were similarly significant (P<0.05). The prediction accuracy of the
mixed model was verified by 10-fold cross validation. The average difference
between measured RT and predicted RT was about 0.10 +/- 0.10 degrees C with the
association coefficient of 0.644, indicating the feasibility of this model in
measuring cattle body temperature. Therefore, an automated technology for
accurately measuring cattle body temperature was accomplished by inventing an
optimal device and establishing the AMSCST system.
PMID- 28426683
TI - Genome-wide identification and characterization of miRNAome from tomato (Solanum
lycopersicum) roots and root-knot nematode (Meloidogyne incognita) during
susceptible interaction.
AB - Root-knot nematodes (RKNs, Meloidogyne spp.) are the most damaging plant
parasites causing severe losses to crop production. The present study reports
genome-wide identification and characterization of both tomato and RKN miRNAs
simultaneously from RKN-infected susceptible tomato roots using high-throughput
sequencing technique. RNAseq data from 11 small RNA libraries derived from 5
disease development stages identified 281 novel miRNAs of tomato in addition to
52 conserved and 4 variants of conserved miRNAs. Additionally, the same set of
RNAseq data identified 38 conserved and 290 novel RKN miRNAs. Both tomato and RKN
miRNAs showed differential expression at 5 stages of disease development based on
digital expression profiles. In tomato, further validation through qRT-PCR
confirmed that majority of miRNAs were significantly upregulated during
susceptible response whereas downregulated during resistance response. The
predicted targets of 8 conserved and 1 novel miRNAs were validated through 5'RLM
RACE. A negative correlation between expression profiles of a few conserved
miRNAs (miR156, miR159, miR164 and miR396) and their targets (SBP, GAMYB-like,
NAC and GRF1 transcription factor) was confirmed. A novel Sly_miRNA996 also
showed a negative correlation with its target MYB-like transcription factor.
These results indicate that the conserved and novel tomato miRNAs are involved in
regulating developmental changes in host root during RKN infection. In RKN, the
targets of conserved miRNAs were also predicted and a few of their predicted
target genes are known to be involved in nematode parasitism. Further, the
potential roles of both tomato and RKN miRNAs have been discussed.
PMID- 28426684
TI - Long-term results after transplantation of pediatric liver grafts from donation
after circulatory death donors.
AB - BACKGROUND: Liver grafts from donation after circulatory death (DCD) donors are
increasingly accepted as an extension of the organ pool for transplantation.
There is little data on the outcome of liver transplantation with DCD grafts from
a pediatric donor. The objective of this study was to assess the outcome of liver
transplantation with pediatric DCD grafts and to compare this with the outcome
after transplantation of livers from pediatric donation after brain death (DBD)
donors. METHOD: All transplantations performed with a liver from a pediatric
donor (<=16 years) in the Netherlands between 2002 and 2015 were included.
Patient survival, graft survival, and complication rates were compared between
DCD and DBD liver transplantation. RESULTS: In total, 74 liver transplantations
with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The
median donor warm ischemia time (DWIT) was 24 min (range 15-43 min). Patient
survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD
grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD
versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have
been rejected for transplantation when the DWIT >=30 min (n = 4), the 10-year
graft survival rate would have been 81% after DCD transplantation. The rate of
non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00).
Other complication rates were also similar between both groups. CONCLUSIONS:
Transplantation of livers from pediatric DCD donors results in good long-term
outcome especially when the DWIT is kept <=30 min. Patient and graft survival
rates are not significantly different between recipients of a pediatric DCD or
DBD liver. Moreover, the incidence of non-anastomotic biliary strictures after
transplantation of pediatric DCD livers is remarkably low.
PMID- 28426685
TI - Human African trypanosomiasis control: Achievements and challenges.
AB - Sleeping sickness, also known as human African trypanosomiasis (HAT), is a
neglected disease that impacts 70 million people living in 1.55 million km2 in
sub-Saharan Africa. Since the beginning of the 20th century, there have been
multiple HAT epidemics in sub-Saharan Africa, with the most recent epidemic in
the 1990s resulting in about half a million HAT cases reported between 1990 and
2015. Here we review the status of HAT disease at the current time and the
toolbox available for its control. We also highlight future opportunities under
development towards novel or improved interventions.
PMID- 28426687
TI - Does ethnicity matter in risk and protective factors for suicide attempts and
suicide lethality?
AB - This study explored ethnic differences in risk and protective factors for suicide
attempts, for the major ethnic groups in Singapore, and ethnic differences in
prediction of lethality. Three years of medical records related to suicide
attempters (N = 666) who were admitted to the emergency department of a large
teaching hospital in Singapore were subjected to analysis. Of the sample, 69.2%
were female, 30.8% male; 63.8% Chinese, 15.8% Indian, and 15.0% Malay. Indians
were over-represented in this sample, as compared with the ethnic distribution in
the general population. Ages ranged from 10 to 85 years old (M = 29.7, SD =
16.1). Ethnic differences were found in risk and protective factors, and
perceived lethality of suicide attempts. All available variables were subjected
to regression analyses for Chinese, Indian and Malay attempters to arrive at
parsimonious models for prediction of perceived lethality. The findings were
discussed in regards to implications in assessment of suicide risk and primary
prevention for the multiethnic society in Singapore.
PMID- 28426686
TI - Reactive oxygen species are required for driving efficient and sustained aerobic
glycolysis during CD4+ T cell activation.
AB - The immune system is necessary for protecting against various pathogens. However,
under certain circumstances, self-reactive immune cells can drive autoimmunity,
like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors
to the immunopathology in T1D, and in order to drive optimal T cell activation,
third signal reactive oxygen species (ROS) must be present. However, the role ROS
play in mediating this process remains to be further understood. Recently,
cellular metabolic programs have been shown to dictate the function and fate of
immune cells, including CD4+ T cells. During activation, CD4+ T cells must
transition metabolically from oxidative phosphorylation to aerobic glycolysis to
support proliferation and effector function. As ROS are capable of modulating
cellular metabolism in other models, we sought to understand if blocking ROS also
regulates CD4+ T cell activation and effector function by modulating T cell
metabolism. To do so, we utilized an ROS scavenging and potent antioxidant
manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation
during activation regulates the mTOR/AMPK axis by maintaining AMPK activation,
resulting in diminished mTOR activation and reduced transition to aerobic
glycolysis in diabetogenic splenocytes. These results correlated with decreased
Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate
production. In an adoptive transfer model of T1D, animals treated with MnP
demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell
activation. Our results demonstrate that ROS are required for driving and
sustaining T cell activation-induced metabolic reprogramming, and further support
ROS as a target to minimize aberrant immune responses in autoimmunity.
PMID- 28426688
TI - Vancomycin-associated acute kidney injury: A cross-sectional study from a single
center in China.
AB - OBJECTIVE: The objective of this study was to investigate the current situation
of vancomycin (VAN)-associated acute kidney injury (VA-AKI) in China and identify
the risk factors for VA-AKI, as well as to comprehensively examine the risk
related to concurrent drug use. Further, we assessed the outcomes of patients who
developed VA-AKI and the risk factors for these outcomes. Finally, we aimed to
provide suggestions for improving the prevention and treatment of VA-AKI in
China. METHODS: We conducted a retrospective observational study of inpatients
who had been treated with VAN between January 2013 and December 2013 at Peking
University First Hospital. AKI was defined as an increase in SCr of >=0.3 mg/dl
(>=26.5 MUmol/l) within 48 hours or an increase to >=1.5 times the baseline
certainly or presumably within the past 7 days. VA-AKI was defined as the
development of AKI during VAN therapy or within 7 days following the termination
of VAN therapy. In addition, we compared patients with NO-AKI, who did not
develop AKI during their hospitalization, with those with VA-AKI. RESULTS: Of the
934 patients treated with VAN during their hospital stay, 740 were included in
this study. Among those excluded, 38.1% (74/194) were excluded because of a lack
of data on serum creatinine (SCr). Among the included patients, 120 had confirmed
VA-AKI, with an incidence of 16.2% (120/740). Multiple logistic regression
analysis revealed that an elevated baseline estimated glomerular filtration rate
(eGFR) (odds ratio [OR] = 1.009; p = 0.017) and concomitant vasopressor therapy
(OR = 2.942; p = 0.009), nitrate use (OR = 2.869; p = 0.007), imipenem-cilastatin
treatment (OR = 4.708; p = 0.000), and contrast medium administration (OR = 6.609
p = 0.005) were independent risk factors for VA-AKI; in addition, the receipt of
orthopedic/trauma/burn surgery (OR = 0.3575; p = 0.011) and concomitant compound
glycyrrhizin use (OR = 0.290; p = 0.017) were independent protective factors for
VA-AKI. Multiple logistic regression analysis also demonstrated that among the
patients who developed VA-AKI, coronary heart disease (CHD) (OR = 12.6; p =
0.006) and concomitant vasopressor therapy (OR = 15.4; p = 0.001) were
independent risk factors for death. We also evaluated the factors influencing
improvement of renal function. Multiple logistic regression analysis demonstrated
that CHD (OR = 8.858, p = 0.019) and concomitant contrast medium administration
(OR = 9.779, p = 0.005) were independent risk factors and that simultaneous beta
blocker treatment (OR = 0.124, p = 0.001) was an independent protective factor
for improvement of renal function. CONCLUSION: Patients treated with VAN received
insufficient monitoring of SCr and inadequate therapeutic drug monitoring. We
recommend that hospitals increase their investment in clinical pharmacists. An
elevated baseline eGFR and concomitant vasopressor therapy, nitrate use, imipenem
cilastatin treatment, and contrast medium administration were independent risk
factors for VA-AKI; in addition, orthopedic/trauma/burn surgery and concomitant
compound glycyrrhizin use were independent protective factors for VA-AKI.
PMID- 28426689
TI - Preference index supported by motivation tests in Nile tilapia.
AB - The identification of animal preferences is assumed to provide better rearing
environments for the animals in question. Preference tests focus on the frequency
of approaches or the time an animal spends in proximity to each item of the
investigated resource during a multiple-choice trial. Recently, a preference
index (PI) was proposed to differentiate animal preferences from momentary
responses (Sci Rep, 2016, 6:28328, DOI: 10.1038/srep28328). This index also
quantifies the degree of preference for each item. Each choice response is also
weighted, with the most recent responses weighted more heavily, but the index
includes the entire bank of tests, and thus represents a history-based approach.
In this study, we compared this PI to motivation tests, which consider how much
effort is expended to access a resource. We performed choice tests over 7
consecutive days for 34 Nile tilapia fish that presented with different colored
compartments in each test. We first detected the preferred and non-preferred
colors of each fish using the PI and then tested their motivation to reach these
compartments. We found that fish preferences varied individually, but the results
were consistent with the motivation profiles, as individual fish were more
motivated (the number of touches made on transparent, hinged doors that prevented
access to the resource) to access their preferred items. On average, most of the
34 fish avoided the color yellow and showed less motivation to reach yellow and
red colors. The fish also exhibited greater motivation to access blue and green
colors (the most preferred colors). These results corroborate the PI as a
reliable tool for the identification of animal preferences. We recommend this
index to animal keepers and researchers to identify an animal's preferred
conditions.
PMID- 28426690
TI - Phenotypic characterization and anticancer capacity of CD8+ cytokine-induced
killer cells after antigen-induced expansion.
AB - Cytokine-induced killer cells (CIK) have been used in clinic for adoptive
immunotherapy in a variety of malignant tumors and have improved the prognosis of
cancer patients. However, there are individual differences in the CIK cell
preparations including the obvious differences in the ratio of effector CIK cells
among different cancer patients. Infusion of such heterogeneous immune cell
preparation is an important factor that would affect the therapeutic efficacy. We
report here the enrichment and expansion of CD8+ cells from CIK cells cultured
for one week using magnetic activated cell sorting (MACS). These enriched CD8+
CIK cells expressed T cell marker CD3 and antigen recognition receptor NKG2D.
Phenotypic analysis showed that CD8+ CIK cells contained 32.4% of CD3+ CD56+
natural killer (NK)-like T cells, 23.6% of CD45RO+ CD28+, and 50.5% of CD45RA+
CD27+ memory T cells. In vitro cytotoxic activity assay demonstrated that the
enriched CD8+ CIK cells had significant cytotoxic activity against K562 cells and
five ovarian cancer cell lines. Intriguingly, CD8+ CIK cells had strong cytotoxic
activity against OVCAR3 cells that has weak binding capability to NKG2D. Flow
cytometry and quantitative RT-PCR analysis revealed that OVCAR3 cells expressed
HLA-I and OCT4 and Sox2, suggesting that CD8+ CIK cells recognize surface antigen
via specific T cell receptor and effectively kill the target cells. The results
suggest that transplantation of such in vitro enriched and expanded OCT4-specific
CD8+ CIK cells may improve the specific immune defense mechanism against cancer
stem cells, providing a novel avenue of cancer stem cell targeted immunotherapy
for clinical treatment of ovarian cancer.
PMID- 28426691
TI - Climatic factors driving vegetation declines in the 2005 and 2010 Amazon
droughts.
AB - Along with global climate change, the occurrence of extreme droughts in recent
years has had a serious impact on the Amazon region. Current studies on the
driving factors of the 2005 and 2010 Amazon droughts has focused on the influence
of precipitation, whereas the impacts of temperature and radiation have received
less attention. This study aims to explore the climate-driven factors of
Amazonian vegetation decline during the extreme droughts using vegetation index,
precipitation, temperature and radiation datasets. First, time-lag effects of
Amazonian vegetation responses to precipitation, radiation and temperature were
analyzed. Then, a multiple linear regression model was established to estimate
the contributions of climatic factors to vegetation greenness, from which the
dominant climate-driving factors were determined. Finally, the climate-driven
factors of Amazonian vegetation greenness decline during the 2005 and 2010
extreme droughts were explored. The results showed that (i) in the Amazon
vegetation greenness responded to precipitation, radiation and temperature, with
apparent time lags for most averaging interval periods associated with vegetation
index responses of 0-4, 0-9 and 0-6 months, respectively; (ii) on average, the
three climatic factors without time lags explained 27.28+/-21.73% (mean+/-1 SD)
of vegetation index variation in the Amazon basin, and this value increased by
12.22% and reached 39.50+/-27.85% when time lags were considered; (iii)
vegetation greenness in this region in non-drought years was primarily affected
by precipitation and shortwave radiation, and these two factors altogether
accounted for 93.47% of the total explanation; and (iv) in the common epicenter
of the two droughts, pixels with a significant variation in precipitation,
radiation and temperature accounted for 36.68%, 40.07% and 10.40%, respectively,
of all pixels showing a significant decrease in vegetation index in 2005, and
15.69%, 2.01% and 45.25% in 2010, respectively. Overall, vegetation greenness
declines during the 2005 and 2010 extreme droughts were adversely influenced by
precipitation, radiation and temperature; this study provides evidence of the
influence of multiple climatic factors on vegetation during the 2005 and 2010
Amazon droughts.
PMID- 28426692
TI - What is adaptation by natural selection? Perspectives of an experimental
microbiologist.
AB - Ever since Darwin, the role of natural selection in shaping the morphological,
physiological, and behavioral adaptations of animals and plants across
generations has been central to understanding life and its diversity. New
discoveries have shown with increasing precision how genetic, molecular, and
biochemical processes produce and express those organismal features during an
individual's lifetime. When it comes to microorganisms, however, understanding
the role of natural selection in producing adaptive solutions has historically
been, and sometimes continues to be, contentious. This tension is curious because
microbes enable one to observe the power of adaptation by natural selection with
exceptional rigor and clarity, as exemplified by the burgeoning field of
experimental microbial evolution. I trace the development of this field, describe
an experiment with Escherichia coli that has been running for almost 30 years,
and highlight other experiments in which natural selection has led to interesting
dynamics and adaptive changes in microbial populations.
PMID- 28426694
TI - Prediction of atherosclerotic cardiovascular disease mortality in a nationally
representative cohort using a set of risk factors from pooled cohort risk
equations.
AB - The American College of Cardiology/American Heart Association developed Pooled
Cohort equations to estimate atherosclerotic cardiovascular disease (ASCVD) risk.
It is unclear how well the equations predict ASCVD mortality in a nationally
representative cohort. We used the National Health and Nutrition Examination
Survey (NHANES) 1988-1994 and Linked Mortality through 2006 (n = 6,644). Among
participants aged 40-79 years without ASCVD at baseline, we used Cox proportional
hazard models to estimate the 10-year probability of ASCVD death by sex and race
ethnicity (non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican
American (MA)). We estimated the discrimination and calibration for each sex-race
ethnicity model. We documented 288 ASCVD deaths during 62,335 person years. The
Pooled Cohort equations demonstrated moderate to good discrimination for ASCVD
mortality, with modified C-statistics of 0.716 (95% CI 0.663-0.770), 0.794 (0.734
0.854), and 0.733 (0.654-0.811) for NHW, NHB and MA men, respectively. The
corresponding C-statistics for women were 0.781 (0.718-0.844), 0.702 (0.633
0.771), and 0.789 (CI 0.721-0.857). Modified Hosmer-Lemeshow chi2 suggested
adequate calibration for NHW, NHB and MA men, and MA women (p-values: 0.128,
0.295, 0.104 and 0.163 respectively). The calibration was inadequate for NHW and
NHB women (p<0.05). In this nationally representative cohort, the Pooled Cohort
equations performed adequately to predict 10-year ASCVD mortality for NHW and NHB
men, and MA population, but not for NHW and NHB women.
PMID- 28426693
TI - Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung
maturation in mice.
AB - BACKGROUND: Oxygen supply as a lifesaving intervention is frequently used to
treat preterm infants suffering additionally from possible prenatal or perinatal
pathogen features. The impact of oxygen and/or physical lung injury may influence
the morphological lung development, leading to a chronic postnatal lung disease
called bronchopulmonary dysplasia (BPD). At present different experimental BPD
models are used. However, there are no systematic comparative studies regarding
different influences of oxygen on morphological lung maturation. OBJECTIVE: We
investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on
morphological lung maturation based on stereological parameters, to find out
which model best reflects morphological changes in lung development comparable
with alterations found in BPD. METHODS: Pregnant mice were exposed to normoxia,
the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore,
pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or
to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all
pups at 14 days after birth. RESULTS: Compared to controls (No/No) 1) the lung
volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the
volume weighted mean volume of the parenchymal airspaces was significantly higher
in the Hypo/Hyper group, 3) the total air space volume was significantly lower in
the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed
significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall
thickness of septa showed the highest values in the Hypo/Hyper group without
reaching significance, 6) the volume density and the volume weighted mean volume
of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly
lower in the Hypo/Hyper group. CONCLUSION: Prenatal hypoxia and postnatal
hyperoxia differentially influence the maturation of lung parenchyma. In 14 day
old mice a significant retardation of morphological lung development leading to
BPD-like alterations indicated by different parameters was only seen after
hypoxia and hyperoxia.
PMID- 28426695
TI - A comparative study of pediatric open pyeloplasty, laparoscopy-assisted
extracorporeal pyeloplasty, and robot-assisted laparoscopic pyeloplasty.
AB - PURPOSE: To compare the outcomes of open pyeloplasty (OP), laparoscopy-assisted
extracorporeal (LEXP), and robotic-assisted laparoscopic pyeloplasty (RALP) for
ureteropelvic junction obstruction in pediatric patients. METHODS: We
retrospectively reviewed the age-matched cohort of 30 children who underwent OP,
30 who underwent LEXP, and 10 who underwent RALP at a single institution, from
1996 to 2014. Pre- and post-operative variables including success rate were
compared among surgical groups. RESULTS: The mean age of the patients was 120.2
months, the Society for Fetal Urology grade was 3.6, the anteroposterior diameter
was 3.1 cm, and the renal relative function was 44.0%. The distribution of
laterality, mean body mass index, and preoperative anteroposterior pelvic
diameter on ultrasound did not differ among groups. The mean length of hospital
stay was significantly shorter in the RALP group (3.2 days) than in the OP (6.6
days) and LEXP (5.8 days) groups (p<0.001). The duration of analgesics use was
shorter in the RALP group (1.1 days) than in the other groups (p<0.001). During
the mean follow-up period of 49.0, 20.1, and 16.6 months, the success rate was
96.7%, 89.7%, and 100% in the OP, LEXP, and RALP groups, respectively, although
this difference was not statistically different (p = 0.499). In multivariate
regression analysis, the presence of crossing vessels was the only factor that
decreased the success rate (hazard ratio: 46.09, 95% confidence interval: 2.41
879.6, p = 0.011). CONCLUSIONS: Patients who undergo RALP have a reduced hospital
stay and lower use of pain medication; however, there is no difference in the
success rates for OP, LP, and RALP surgeries. The presence of crossing vessels is
a negative prognostic indicator for surgical outcome regardless of the surgical
method.
PMID- 28426696
TI - Heritability of brain volume on MRI in middle to advanced age: A twin study of
Japanese adults.
AB - Brain atrophy is part of the aging process and accelerated by neurodegenerative
diseases, so an understanding of the background heritability of brain volume is
essential. The purpose of this study was to determine the heritability of brain
volume in middle to advanced age East Asian adults, an age group less studied and
an ethnicity not previously studied. 3T magnetic resonance images were obtained
and volumetric analyses conducted for a total of 74 individuals, 20 monozygotic
twin pairs (mean age 61y min 41y max 75y) and 17 dizygotic twin pairs (mean age
64y min 41y max 85y). Total brain volume and a further seven regions were
assessed, including lobar volumes, lateral divisions, and separated grey and
white matter. Additive genetics and unique environment (AE) models for global
brain volumes including total brain (90%), grey matter (91%) and white matter
(84%) and many lobar volumes demonstrated high heritability in our study
population. Our results present the heritability of brain volume in middle to
advanced age as possibly higher in East Asian adults.
PMID- 28426697
TI - Perceived conflict of interest in health science partnerships.
AB - University scientists conducting research on topics of potential health concern
often want to partner with a range of actors, including government entities, non
governmental organizations, and private enterprises. Such partnerships can
provide access to needed resources, including funding. However, those who observe
the results of such partnerships may judge those results based on who is
involved. This set of studies seeks to assess how people perceive two
hypothetical health science research collaborations. In doing so, it also tests
the utility of using procedural justice concepts to assess perceptions of
research legitimacy as a theoretical way to investigate conflict of interest
perceptions. Findings show that including an industry collaborator has clear
negative repercussions for how people see a research partnership and that these
perceptions shape people's willingness to see the research as a legitimate source
of knowledge. Additional research aimed at further communicating procedures that
might mitigate the impact of industry collaboration is suggested.
PMID- 28426698
TI - Extensive alterations of blood metabolites in pediatric cerebral malaria.
AB - Cerebral malaria (CM) presents as an encephalopathy and is due to infection with
Plasmodium falciparum. Patients are comatose, often with fever, recurrent
seizures and this condition is associated with a high mortality rate. The
etiology of the coma and seizures are poorly understood. Circulating small
molecules and lipids have bioactive functions and alterations in their
concentrations have been implicated in seizure disorders and other forms of
encephalopathy. We carried out a comprehensive analysis of blood metabolites
during CM to explore a biochemical basis of this encephalopathy. A paired
metabolomics analysis was performed on the plasma samples of Malawian children (n
= 11) during CM and at convalescence thirty days later, to identify
differentially abundant molecules associated with CM. We also report plasma
molecules associated with CM mortality (n = 4) compared to survival (n = 19).
Plasma metabolites were identified through ultra high performance liquid
chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry
to maximize compound detection and accuracy and then compared to a library for
identification. We detected a total of 432 small molecules in the plasma and 247
metabolites were significantly differentially abundant between CM and
convalescence (p < 0.05, FDR < 0.10). These represented global changes across
many classes of molecules including lipids, amino acids and hemoglobin
metabolites. We observed significant changes in molecules that could impact
neurologic function during CM; these include increased levels of kynurenate and
decreased indolepropionate, glutamate, arginine and glutamine. Moreover, 1
methylimidazoleacetate, kyurenate, arachidonic acid and dimethylarginine were
associated with mortality (p < 0.05, fold change > 1.2). These results highlight
the broad changes in blood chemistry during CM. We have identified metabolites
that may impact central nervous system physiology and disease outcomes and can be
further explored for their mechanistic roles into the pathophysiology of CM.
PMID- 28426699
TI - Anti-IL-20 monoclonal antibody inhibited inflammation and protected against
cartilage destruction in murine models of osteoarthritis.
AB - Osteoarthritis (OA) is a degenerative joint disease characterized by progressive
destruction of articular cartilage. Interleukin (IL)-20 is a proinflammatory
cytokine involved in the pathogenesis of rheumatoid arthritis. We investigated
the role of IL-20 in OA and evaluated whether anti-IL-20 antibody (7E) treatment
attenuates disease severity in murine models of surgery-induced OA.
Immunohistochemical staining was used to detect IL-20 and its receptors
expression in synovial tissue and cartilage from OA patients, and in OA synovial
fibroblasts (OASFs) and chondrocytes (OACCs) from rodents with surgery-induced
OA. RTQ-PCR and western blotting were used to determine IL-20-regulated OA
associated gene expression in OASFs and OACCs. OA rats and OA mice were treated
with 7E. Arthritis severity was determined based on the degree of cartilage
damage and the arthritis severity score. We found that IL-20 and its receptors
were expressed in OASFs and OACCs. IL-20 induced TNF-alpha, IL-1beta, MMP-1, and
MMP-13 expression by activating ERK-1/2 and JNK signals in OASFs. IL-20 not only
upregulated MCP-1, IL-6, MMP-1, and MMP-13 expression, but also downregulated
aggrecan, type 2 collagen, TGF-beta, and BMP-2 expression in OACCs. Arthritis
severity was significantly lower in 7E-treated OA rats, and 7E- or MSC-treated OA
mice. Therefore, we concluded that IL-20 was involved in the progression and
development of OA through inducing proinflammatory cytokines and OA-associated
gene expression in OASFs and OACCs. 7E reduced the severity of arthritis in
murine models of surgery-induced OA. Our findings provide evidence that IL-20 is
a novel target and that 7E is a potential therapeutic agent for OA.
PMID- 28426700
TI - Southern Tunisia: A still high endemicity area for hepatitis A.
AB - BACKGROUND: Hepatitis A (HAV) and E (HEV) viruses are responsible for enterically
transmitted hepatitis. Tunisia is reported to be of intermediate endemicity for
HAV and of low seroprevalence for HEV; however, data from rural areas of South
Tunisia are lacking. METHODS: Sera from 216 asymptomatic pregnant women and from
92 patients with acute hepatitis were collected between October 2014 and November
2015. Total and IgM anti-HAV immunoglobulins and anti-HEV IgG and IgM were
investigated. Anti-HAV IgM-positive samples were subjected to RT-PCR targeting
the VP1/2A region and sequenced. HEV IgM positive samples and all samples from
acute hepatitis patients were assessed for HEV RNA. RESULTS: Among pregnant women
(mean age 32+/-8), HAV seroprevalence was 98.6%, none presented anti-HAV IgM; HEV
seroprevalence was 5.1% and three presented weakly reactive anti-HEV IgM without
detectable RNA. Among acute hepatitis patients (mean age 18.5 +/- 14), HEV
seroprevalence was 19,5%, none presented anti-HEV IgM, nor HEV RNA. HAV
seroprevalence exceeded 90% by age 5 and acute HAV infection was detected in 20
patients (21,7%), younger than patients with other hepatitis causes (9,8 years
vs. 20,4 years, p = 0,004); 65% were male. Most acute HAV infections were
observed in a coastal area where HAV infections represented 52% of hepatitis
etiology. Phylogenetic analysis identified genotype IA strains, clustering close
to previously published Tunisian sequences. CONCLUSION: The present study
confirmed a low HEV endemicity and evidenced a still high level of HAV
circulation in Southern Tunisia, suggesting distinct dissemination patterns for
these viruses.
PMID- 28426701
TI - Exploratory study on the effect of osteoactivin on muscle regeneration in a rat
volumetric muscle loss model.
AB - Wounds causing extensive injury loss of muscle, also known as volumetric muscle
loss (VML), are frequently associated with high-energy civilian trauma and combat
related extremity injuries. Currently, no effective clinical therapy is available
for promoting de novo muscle tissue regeneration to restore muscle function
following VML. Recent studies have shown evidence that osteoactivin (OA), a
transmembrane glycoprotein, has the ability to prevent skeletal muscle atrophy in
response to denervation. Therefore the objective of this study is to investigate
the potential regenerative effect of OA embedded and delivered via a cross-linked
gelatin hydrogel within a volumetric tibialis anterior muscle defect in a rat
model. After 4 weeks, however, no evidence for muscle formation was found in
defects treated with either low (5 MUg/ml) or high (50 MUg/ml) OA. It is possible
that a different delivery scaffold, delivery kinetics, or OA concentration may
have yielded an alternate outcome, or it is also possible that the
spaciostructural environment of VML, or the local (versus systemic) delivery of
OA, simply does not support any potential regenerative activity of OA in VML.
Together with prior work, this study demonstrates that an efficacious and
scalable therapy for regenerating muscle volume and function in VML remains a
veritable clinical challenge worthy of continued future research efforts.
PMID- 28426702
TI - Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease
activity: A prospective, non-randomized pilot study.
AB - Natalizumab is an effective therapy for multiple sclerosis (MS). Its
effectiveness has been demonstrated in several clinical and imaging studies. The
objective of this study was to further demonstrate the efficacy of natalizumab
using a comprehensive battery of clinical and imaging markers in the same cohort
of patients followed longitudinally, hence capturing the multi-faceted nature of
the MS disease process. A prospective, open-label, pilot study of 20 MS patients
treated with natalizumab was conducted. High resolution MRI, Symbol-Digit
Modalities Test (SDMT), and Optical Coherence Tomography (OCT) scans were
obtained at baseline, 48, and 96 weeks. 15 patients completed the study.
Natalizumab treatment decreased Expanded Disability Status Scale score (EDSS) and
no change in SDMT, Brain Parenchymal Fraction (BPF), or any of the OCT markers of
retinal degeneration was observed. Thalamic and whole brain volume as assessed by
Percentage Brain Volume Change (PBVC) showed continuous deterioration. Higher
baseline T2 lesion load correlated with increased rate of PBVC at 96-weeks (r =
0.566, R2 = 0.320, p = 0.035) and thalamic volume loss (r = -0.586, R2 = 0.344, p
= 0.027). Most patients, 93%, achieved no evidence of disease activity (NEDA) at
2 years, likely due to early disease duration and lower initial baseline lesion
load. This study further demonstrates stabilization of clinical and imaging
markers of disease activity during natalizumab treatment.
PMID- 28426703
TI - Effects of over-expressing a native gene encoding 5-enolpyruvylshikimate-3
phosphate synthase (EPSPS) on glyphosate resistance in Arabidopsis thaliana.
AB - Widespread overuse of the herbicide glyphosate, the active ingredient in
RoundUp(r), has led to the evolution of glyphosate-resistant weed biotypes, some
of which persist by overproducing the herbicide's target enzyme, 5
enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS is a key enzyme in the
shikimic acid pathway for biosynthesis of aromatic amino acids, lignin, and
defensive compounds, but little is known about how overproducing EPSPS affects
downstream metabolites, growth, or lifetime fitness in the absence of glyphosate.
We are using Arabidopsis as a model system for investigating phenotypic effects
of overproducing EPSPS, thereby avoiding confounding effects of genetic
background or other mechanisms of herbicide resistance in agricultural weeds.
Here, we report results from the first stage of this project. We designed a
binary vector expressing a native EPSPS gene from Arabidopsis under control of
the CaMV35S promoter (labelled OX, for over-expression). For both OX and the
empty vector (labelled EV), we obtained nine independent T3 lines. Subsets of
these lines were used to characterize glyphosate resistance in greenhouse
experiments. Seven of the nine OX lines exhibited enhanced glyphosate resistance
when compared to EV and wild-type control lines, and one of these was discarded
due to severe deformities. The remaining six OX lines exhibited enhanced EPSPS
gene expression and glyphosate resistance compared to controls. Glyphosate
resistance was correlated with the degree of EPSPS over-expression for both
vegetative and flowering plants, indicating that glyphosate resistance can be
used as a surrogate for EPSPS expression levels in this system. These findings
set the stage for examination of the effects of EPSPS over-expression on fitness
related traits in the absence of glyphosate. We invite other investigators to
contact us if they wish to study gene expression, downstream metabolic effects,
and other questions with these particular lines.
PMID- 28426704
TI - Population effect model identifies gene expression predictors of survival
outcomes in lung adenocarcinoma for both Caucasian and Asian patients.
AB - BACKGROUND: We analyzed and integrated transcriptome data from two large studies
of lung adenocarcinomas on distinct populations. Our goal was to investigate the
variable gene expression alterations between paired tumor-normal tissues and
prospectively identify those alterations that can reliably predict lung disease
related outcomes across populations. METHODS: We developed a mixed model that
combined the paired tumor-normal RNA-seq from two populations. Alterations in
gene expression common to both populations were detected and validated in two
independent DNA microarray datasets. A 10-gene prognosis signature was developed
through a l1 penalized regression approach and its prognostic value was evaluated
in a third independent microarray cohort. RESULTS: Deregulation of apoptosis
pathways and increased expression of cell cycle pathways were identified in
tumors of both Caucasian and Asian lung adenocarcinoma patients. We demonstrate
that a 10-gene biomarker panel can predict prognosis of lung adenocarcinoma in
both Caucasians and Asians. Compared to low risk groups, high risk groups showed
significantly shorter overall survival time (Caucasian patients data: HR = 3.63,
p-value = 0.007; Asian patients data: HR = 3.25, p-value = 0.001). CONCLUSIONS:
This study uses a statistical framework to detect DEGs between paired tumor and
normal tissues that considers variances among patients and ethnicities, which
will aid in understanding the common genes and signalling pathways with the
largest effect sizes in ethnically diverse cohorts. We propose multifunctional
markers for distinguishing tumor from normal tissue and prognosis for both
populations studied.
PMID- 28426706
TI - Bearing-based localization for leader-follower formation control.
AB - The observability of the leader robot system and the leader-follower formation
control are studied. First, the nonlinear observability is studied for when the
leader robot observes landmarks. Second, the system is shown to be completely
observable when the leader robot observes two different landmarks. When the
leader robot system is observable, multi-robots can rapidly form and maintain a
formation based on the bearing-only information that the follower robots observe
from the leader robot. Finally, simulations confirm the effectiveness of the
proposed formation control.
PMID- 28426705
TI - An automated algorithm for the detection of cortical interruptions on high
resolution peripheral quantitative computed tomography images of finger joints.
AB - OBJECTIVES: To introduce a fully-automated algorithm for the detection of small
cortical interruptions (>=0.246mm in diameter) on high resolution peripheral
quantitative computed tomography (HR-pQCT) images, and to investigate the
additional value of manual correction of the automatically obtained contours
(semi-automated procedure). METHODS: Ten metacarpophalangeal joints from seven
patients with rheumatoid arthritis (RA) and three healthy controls were imaged
with HR-pQCT. The images were evaluated by an algorithm according to the fully-
and semi-automated procedure for the number and surface of interruptions per
joint. Reliability between the fully- and semi-automated procedure and between
two independent operators was tested using intra-class correlation coefficient
(ICC) and the proportion of matching interruptions. Validity of single
interruptions detected was tested by comparing it to visual scoring, as gold
standard. The positive predictive value (PPV) and sensitivity were calculated.
RESULTS: The median number of interruptions per joint was 14 (range 2 to 59) and
did not significantly differ between the fully- and semi-automated procedure (p =
0.37). The median interruption surface per joint was significantly higher with
the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and
6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi
automated procedure for both the number and surface of interruptions (ICC>=0.95)
and the proportion of matching interruptions was high (>=76%). Also the inter
operator reliability was almost perfect (ICC>=0.97, proportion of matching
interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from
69.7% to 76.3%. Most interruptions detected with the algorithm, did show an
interruption on a 2D grayscale image. However, this interruption did not meet the
criteria of an interruption with visual scoring. CONCLUSION: The algorithm for HR
pQCT images detects cortical interruptions, and its interruption surface.
Reliability and validity was comparable for the fully- and semi-automated
procedures. However, we advise the use of the semi-automated procedure to assure
quality. The algorithm is a promising tool for a sensitive and objective
assessment of cortical interruptions in finger joints assessed by HR-pQCT.
PMID- 28426707
TI - Rare cell isolation and recovery on open-channel microfluidic chip.
AB - The ability to accurately detect and analyze rare cells in a cell population is
critical not only for the study of disease progression but also for next flow
cytometry systems in clinical application. Here, we report the development of a
prototype device, the 'Rare cell sorter', for isolating and recovering single
rare cells from whole blood samples. On this device, we utilized an open-channel
microfluidic chip for rare cell isolation. And the advantage of open-channel
allows us to recover the isolated rare cell directly from the chip. We set the
circulating tumor cell (CTC) as a target cell. For the clinical experiment, CTCs
were isolated from blood samples collected from patients with metastatic breast
cancer and healthy volunteers. There was a significant difference in the number
of CTCs between the patients with metastatic breast cancer and healthy
volunteers. To evaluate the damage to cells during isolation and recovery, we
performed an RNA integrity assay using RNA extracted from CTCs recovered from the
chip and found that our process for single CTC isolation and recovery is mild
enough for gene analysis of CTCs.
PMID- 28426708
TI - Let's decide together: Differences between individual and joint delay
discounting.
AB - This study addressed the question whether or not social collaboration has an
effect on delay discounting, the tendency to prefer sooner but smaller over later
but larger delivered rewards. We applied a novel paradigm in which participants
executed choices between two gains in an individual and in a dyadic decision
making condition. We observed how participants reached mutual consent via
joystick movement coordination and found lower discounting and a higher
decisions' efficiency. In order to establish the underlying mechanism for dyadic
variation, we further tested whether these differences emerge from social
facilitation or inner group interchange.
PMID- 28426709
TI - Pdgfrb is a direct regulatory target of TGFbeta signaling in atrioventricular
cushion mesenchymal cells.
AB - Cushion formation is the initial step for the development of valvuloseptal
structures in mammalian hearts. TGFbeta signaling plays critical roles in
multiple steps of cushion morphogenesis. We used a newly developed conditional
immortal atrioventricular cushion mesenchymal cell line, tsA58-AVM, to identify
the TGFbeta regulatory target genes through microarray analysis. Expression of
~1350 genes was significantly altered by TGFbeta1 treatment. Subsequent
bioinformatic analysis of TGFbeta activated genes revealed that PDGF-BB signaling
is the top hit as the potential upstream regulator. Among the 37 target
molecules, 10 genes known to be involved in valve development and hemostasis were
selected for quantitative reverse transcription polymerase chain reaction (qRT
PCR) analysis. Our results confirmed that they are all upregulated by TGFbeta1
stimulation in tsA58-AVM cells and in primary atrioventricular cushion cells. We
focused on examining regulation of Pdgfrb by TGFbeta1, which encodes a tyrosine
kinase receptor for PDGF-BB. We found that the ~150bp Pdgfrb promoter can respond
to TGFbeta stimulation and that this response relies on the two SP1 binding sites
within the promoter. Co-immunoprecipitation analysis confirmed SP1 interacts with
SMAD2 in a TGFbeta-dependent fashion. Furthermore, SMAD2 is associated with the
Pdgfrb promoter and this association is diminished by knocking down expression of
Sp1. Our data therefore collectively suggest that upon TGFbeta stimulation, SP1
recruits SMAD2 to the promoter of Pdgfrb to up-regulate its expression and thus
Pdgfrb is a direct downstream target of the TGFbeta/SMAD2 signaling.
PMID- 28426710
TI - Change in iron metabolism in rats after renal ischemia/reperfusion injury.
AB - Previous studies have indicated that hepcidin, which can regulate iron efflux by
binding to ferroportin-1 (FPN1) and inducing its internalization and degradation,
acts as the critical factor in the regulation of iron metabolism. However, it is
unknown whether hepcidin is involved in acute renal ischemia/reperfusion injury
(IRI). In this study, an IRI rat model was established via right renal excision
and blood interruption for 45 min in the left kidney, and iron metabolism indexes
were examined to investigate the change in iron metabolism and to analyze the
role of hepcidin during IRI. From 1 to 24 h after renal reperfusion, serum
creatinine and blood urea nitrogen were found to be time-dependently increased
with different degrees of kidney injury. Regular variations in iron metabolism
indexes in the blood and kidneys were observed in renal IRI. Renal iron content,
serum iron and serum ferritin increased early after reperfusion and then
declined. Hepcidin expression in the liver significantly increased early after
reperfusion, and its serum concentration increased beginning at 8 h after
reperfusion. The splenic iron content decreased significantly in the early stage
after reperfusion and then increased time-dependently with increasing reperfusion
time, and the hepatic iron content showed a decrease in the early stage after
reperfusion. The early decrease of the splenic iron content and hepatic iron
content might indicate their contribution to the increase in serum iron in renal
IRI. In addition, the duodenal iron content showed time-dependently decreased
since 12 h after reperfusion in the IRI groups compared to the control group.
Along with the spleen, the duodenum might contribute to the decrease in serum
iron in the later stage after reperfusion. The changes in iron metabolism indexes
observed in our study demonstrate an iron metabolism disorder in renal IRI, and
hepcidin might be involved in maintaining iron homeostasis in renal IRI. These
findings might suggest a self-protection mechanism regulating iron homeostasis in
IRI and provide a new perspective on iron metabolism in attenuating renal IRI.
PMID- 28426711
TI - Proinsulin is stable at room temperature for 24 hours in EDTA: A clinical
laboratory analysis (adAPT 3).
AB - AIMS: Reference laboratories advise immediate separation and freezing of samples
for the assay of proinsulin, which limit its practicability for smaller centres.
Following the demonstration that insulin and C-peptide are stable in EDTA at room
temperature for at least 24hours, we undertook simple stability studies to
establish whether the same might apply to proinsulin. METHODS: Venous blood
samples were drawn from six adult women, some fasting, some not, aliquoted and
assayed immediately and after storage at either 4 degrees C or ambient
temperature for periods from 2h to 24h. RESULTS: There was no significant
variation or difference with storage time or storage condition in either
individual or group analysis. CONCLUSION: Proinsulin appears to be stable at room
temperature in EDTA for at least 24h. Immediate separation and storage on ice of
samples for proinsulin assay is not necessary, which will simplify sample
transport, particularly for multicentre trials.
PMID- 28426712
TI - The culturable mycobiota of Flabellia petiolata: First survey of marine fungi
associated to a Mediterranean green alga.
AB - Algae-inhabiting marine fungi represent a taxonomically and ecologically
interesting group of microorganisms still largely neglected, especially in
temperate regions. The aim of this study was to isolate and to identify the
culturable mycobiota associated with Flabellia petiolata, a green alga frequently
retrieved in the Mediterranean basin. Twenty algal thalli were collected from two
different sampling sites in the Mediterranean Sea (Elba Island, Italy). A
polyphasic approach showed the presence of a relevant alga-associated mycobiota
with 64 taxa identified. The fungal isolates belonged mainly to Ascomycota (61
taxa), while only three Basidiomycota were detected. The phylogenetic position of
sterile mycelia and cryptic taxa, inferred on the basis of LSU partial region,
highlighted the presence of putative new phylogenetic lineages within
Dothideomycetes and Sordariomycetes. This work represents the first quali
quantitative analysis of the culturable mycobiota associated to a green alga in
the Mediterranean Sea.
PMID- 28426713
TI - Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the
insulin signaling pathway.
AB - Knockout of metallothionein (MT) genes contributes to a heavier body weight in
early life and the potential to become obese through the intake of a high fat
diet (HFD) in mice. It has thus been suggested that MT genes regulate the
formation of adipose tissue, which would become the base for later HFD-induced
obesity. We evaluated the fat pads of mice during the lactation stage. The fat
mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of
wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to
silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes
were transiently upregulated during adipocyte differentiation, and the siRNA
pretreatment led to the suppression of the expression of both MT mRNAs and
proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused
proliferation of post-confluent preadipocytes; these effects were suppressed by
an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA
promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the
insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting
from MT-gene silencing was inhibited by pretreatment with an antioxidant, N
acetylcysteine, used as a substitute for antioxidant protein MTs. These results
suggest that interference in MT expression enhanced the activation of the insulin
signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes.
PMID- 28426714
TI - A genetic risk score for CAD, psychological stress, and their interaction as
predictors of CAD, fatal MI, non-fatal MI and cardiovascular death.
AB - BACKGROUND: Psychological stress is an independent risk factor for cardiovascular
disease (CVD), but the mechanism by which stress is associated with CVD is not
entirely understood. Although genetic factors are implied in both stress
responsivity and cardiovascular reactivity, no studies to date have investigated
their interactions with stress for cardiovascular end points. The objective was
to elucidate the association and interactions between a genetic risk score (GRS),
individual genetic variants and stress for three cardiovascular end points:
coronary artery disease (CAD), fatal myocardial infarction (MI), non-fatal MI,
and cardiovascular death. METHODS AND FINDINGS: 18,559 participants from the
Malmo Diet Cancer Study, a population-based prospective study, were included in
the analyses. Cox proportional hazards regression models were used and adjusted
for a large number of known predictors of cardiovascular end points. Mean follow
up time in years was 14.6 (CAD; n = 1938), 14.8 (fatal MI; n = 436), 14.8 (non
fatal MI; n = 1108), and 15.1 (cardiovascular death; n = 1071) respectively. GRS
was significantly associated with increased risks of CAD (top quartile hazard
ratio [HR], 1.72; 95% confidence interval [CI], 1.51-1.96), fatal MI (top
quartile HR, 1.62; 95%CI, 1.23-2.15), non-fatal MI (top quartile HR, 1.55; 95%CI,
1.31-1.84), and cardiovascular death (top quartile HR, 1.29; 95%CI, 1.08-1.53).
Stress was not independently associated with any end point and did not interact
with GRS. Four individual genetic variants interacted unfavorably with stress for
end points with mortality outcomes. CONCLUSION: A GRS composed of 50 SNPs and
predictive of CAD was found for the first time to also strongly predict fatal MI,
non-fatal MI and cardiovascular death. A stress-sensitive component of the GRS
was isolated on the basis of individual genetic variants that interacted
unfavorably with stress.
PMID- 28426715
TI - Acute hypoxia influences collagen and matrix metalloproteinase expression by
human keratoconus cells in vitro.
AB - Keratoconus (KC) is a progressive corneal ectasia linked to thinning of the
central cornea. Hard contact lenses, rigid gas permeable lenses, and scleral
lenses are the primary treatment modalities for early to mid- stages of KC to
correct refractive error and astigmatism that develops as a result of an
irregular corneal structure. These treatments are associated with significant
drawbacks, including reduced availability of the tear film and oxygen to the
corneal epithelium and stroma. However, it remains unknown whether hypoxia
affects corneal integrity in the KC pathobiology. A number of studies have
associated elevated oxidative stress with KC both in vitro and ex vivo. We
hypothesized that KC-derived corneal fibroblasts are more susceptible to hypoxia
induced oxidative stress compared to healthy controls leading to exacerbation of
corneal thinning in KC. This study investigated the effects of hypoxia on ECM
secretion, assembly, and matrix metalloproteinase (MMP) expression in human
corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs) in vitro.
HCFs and HKCs were cultured in 3D constructs for 3 weeks and maintained or
transferred to normoxic (21% O2) or hypoxic (2% O2) conditions, respectively, for
1 additional week. At the 4 week time-point, constructs were isolated and probed
for Collagen I, III, and V, keratocan and MMP-1, -2, -3, -9, and -13, as well as
hypoxia markers, hypoxia inducible factor-1alpha and lactoferrin. Conditioned
media was also collected and probed for Collagen I, III, and V by Western blot.
Thickness of the ECM assembled by HCFs and HKCs was measured using
immunofluorescence microscopy. Results showed that hypoxia significantly reduced
Collagen I secretion in HKCs, as well as upregulated the expression of MMP-1 and
2 with no significant effects on MMP-3, -9, or -13. ECM thickness was reduced in
both cell types following 1 week in a low oxygen environment. Our study shows
that hypoxia influences collagen and MMP expression by HKCs, which may have
consequential effects on ECM structure in the context of KC.
PMID- 28426716
TI - The yin and yang of leishmaniasis control.
PMID- 28426717
TI - Adjusting cryodiluent composition for improved post-thaw quality of rabbit
spermatozoa.
AB - Improved fertility following artificial insemination with frozen-thawed
spermatozoa would offer rabbit producers faster genetic improvement. Previous
work investigating cryoprotectants for rabbit spermatozoa have reported
inconsistent results. Semen was collected from three rabbit bucks by artificial
vagina and frozen using a standard procedure with varied cryodiluent components.
Post-thaw analysis encompassed motility, sperm kinematic parameters and acrosome
and membrane integrity. Spermatozoa were evaluated at 0, 2 and 4 h after thawing.
Experiment 1 compared diluents with 3.5% dimethyl sulfoxide (DMSO), 1.5%
acetamide, 1.75% DMSO + 0.75% acetamide or 3.5% DMSO + 1.5% acetamide. The
treatment that resulted in the highest post-thaw motility (P<0.001) and acrosome
integrity (P<0.001) was DMSO alone. Experiment 2 compared 3.5, 7 and 10% DMSO in
the cryodiluent. The best post-thaw sperm motility (P<0.001) and linearity (P =
.002) was in 3.5% DMSO, while 10% DMSO afforded higher acrosome/membrane
integrity at this last time point (P<0.05). Experiment 3 varied the cryodiluent
to contain either 9 or 17% egg yolk or 9 or 17% low density lipoproteins
extracted from whole egg yolk. The treatment with the best post-thaw result was
17% egg yolk (motility, P = 0.01; acrosome/membrane integrity, P<0.001).
Experiment 4 compared different carbohydrates in the cryodiluent; 50 mM glucose
(TCG), 25 mM glucose with 25 mM sucrose (TCGS low), or 50 mM glucose with 50 mM
sucrose (TCGS high). When data were pooled across time points, TCG had
significantly higher motility than TCGS high (P = 0.021), but was not different
from TCGS low. However, TCG had fewer spermatozoa with intact acrosomes and
membranes than both TCGS low and TCGS high (P = .002). Put together, these
results indicate that the best cryodiluent for rabbit spermatozoa frozen under
the conditions used in this paper is with 7% DMSO and 17% egg yolk in a base
medium containing 25 mM glucose and 25 mM sucrose.
PMID- 28426718
TI - Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in
A/J Min/+ mice.
AB - The International Agency for Research on Cancer has classified red meat as
"probably carcinogenic to humans" (Group 2A). In mechanistic studies exploring
the link between intake of red meat and CRC, heme iron, the pigment of red meat,
is proposed to play a central role as a catalyzer of luminal lipid peroxidation
and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to
investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle
food (dry weight) and 60% powder diet) on Apc-driven intestinal carcinogenesis,
from week 3-13 of age. Muscle food diets did not differentially affect
carcinogenesis in the colon (flat ACF and tumors). In the small intestine, salmon
intake resulted in a lower tumor size and load than did meat from terrestrial
animals (beef, pork or chicken), while no differences were observed between the
effects of white meat (chicken) and red meat (pork and beef). Additional results
indicated that intestinal carcinogenesis was not related to dietary n-6
polyunsaturated fatty acids, intestinal formation of lipid peroxidation products
(thiobarbituric acid reactive substances, TBARS), or cytotoxic effects of fecal
water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to
be relatively low in this study. The greatest tumor load was induced by the
reference diet RM1, underlining the importance of the basic diets in experimental
CRC. The present study in A/J Min/+ mice does not support the hypothesis of a
role of red meat in intestinal carcinogenesis.
PMID- 28426719
TI - Transcriptome of interstitial cells of Cajal reveals unique and selective gene
signatures.
AB - Transcriptome-scale data can reveal essential clues into understanding the
underlying molecular mechanisms behind specific cellular functions and biological
processes. Transcriptomics is a continually growing field of research utilized in
biomarker discovery. The transcriptomic profile of interstitial cells of Cajal
(ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI)
smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow
cytometry, we isolated ICC populations from the murine small intestine and colon
and obtained their transcriptomes. In analyzing the transcriptome, we identified
a unique set of ICC-restricted markers including transcription factors,
epigenetic enzymes/regulators, growth factors, receptors, protein
kinases/phosphatases, and ion channels/transporters. This analysis provides new
and unique insights into the cellular and biological functions of ICC in GI
physiology. Additionally, we constructed an interactive ICC genome browser
(http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To
our knowledge, this is the first online resource that provides a comprehensive
library of all known genetic transcripts expressed in primary ICC. Our genome
browser offers a new perspective into the alternative expression of genes in ICC
and provides a valuable reference for future functional studies.
PMID- 28426720
TI - A new model mimicking persistent HBV e antigen-negative infection using
covalently closed circular DNA in immunocompetent mice.
AB - Despite the availability of an effective vaccine, hepatitis B virus (HBV)
infection remains a major health problem. HBV e antigen (HBeAg)-negative strains
have become prevalent. Previously, no animal model mimicked the clinical course
of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection
model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a
clinical sample and then circularized to form covalently closed circular
(cccDNA). The resulting cccDNA was introduced into the liver of C57BL/6J mice
through hydrodynamic injection. Persistence of the HBeAg-negative infection was
monitored at predetermined time points using HBV-specific markers including HBV
surface antigen (HBsAg), HBeAg, and HBV core antigen (HBcAg) as well as DNA
copies. Throughout the study, pAAV-HBV1.2 was used as a control. In mice injected
with HBeAg-negative cccDNA, the HBV infection rate was 100% at the initial stage.
HBsAg levels increased up to 1 week, at which point levels peaked and dropped
quickly thereafter. In 60% of injected mice, HBsAg and HBcAg persisted for more
than 10 weeks. High numbers of HBV DNA copies were detected in the serum and
liver. Moreover, cccDNA persisted in the liver tissue of HBeAg-negative mice. In
contrast to the pAAV-HBV 1.2 injected mice, no HBeAg was found in mice injected
with HBeAg-negative HBV throughout the study period. These results demonstrate
the first successful establishment of a model of HBeAg-negative HBV-persistent
infection in immunocompetent mice. Compared to pAAV-HBV1.2-injected mice, the
infection persistence and levels of serum virological and biochemical markers
were approximately equal in the model mice. This model will be useful for
mechanistic studies on HBeAg-negative HBV infection and will facilitate the
evaluation of new antiviral drugs.
PMID- 28426721
TI - Diagnosis, treatment and prognosis of small bowel volvulus in adults: A
monocentric summary of a rare small intestinal obstruction.
AB - OBJECTIVES: Small bowel volvulus is a rare disease, which is also challenging to
diagnose. The aims of this study were to characterize the clinical and
radiological features associated with small bowel volvulus and treatment and to
identify risk factors for associated small bowel necrosis. METHODS: Patients with
small bowel volvulus who underwent operations from January 2001 to December 2015
at the First Affiliated Hospital of China Medical University (Shenyang, China)
were reviewed. Clinical, surgical and postsurgical data were registered and
analyzed. RESULTS: Thirty-one patients were included for analysis. Fifteen
patients were female (48.4%), with an average age of 47.7 years (18-79 years).
The clinical signs and symptoms were unspecific and resembled intestinal
obstruction. Clinical examination revealed abdominal distension and/or diffuse
tenderness with or without signs of peritonitis. The use of CT scans, X-rays or
ultrasound did not differ significantly between patients. In 9 of 20 patients
that received abdominal CT scans, "whirlpool sign" on the CT scan was present.
Secondary small bowel volvulus was present in 58.1% of patients, and causes
included bands (3), adhesion (7), congenital anomalies (7) and stromal tumor (1).
Out of the 31 patients, 15 with gangrenous small bowel had to undergo intestinal
resection. Intestinal gangrene was present with higher neutrophils count
(p<0.0001) and the presence of bloody ascites (p = 0.004). Three patients died of
septic shock (9.68%), and the recurrence rate was 3.23%. CONCLUSIONS: To complete
an early and accurate diagnosis, a CT scan plus physical exam seems to be the
best plan. After diagnosis, an urgent laparotomy must be performed to avoid
intestinal necrosis and perforation. After surgery, more than 90% of the patients
can expect to have a favorable prognosis.
PMID- 28426722
TI - Interactions between mitoNEET and NAF-1 in cells.
AB - The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF
1) are required for cancer cell proliferation and resistance to oxidative stress.
NAF-1 and mNT are also implicated in a number of other human pathologies
including diabetes, neurodegeneration and cardiovascular disease, as well as in
development, differentiation and aging. Previous studies suggested that mNT and
NAF-1 could function in the same pathway in mammalian cells, preventing the over
accumulation of iron and reactive oxygen species (ROS) in mitochondria.
Nevertheless, it is unknown whether these two proteins directly interact in
cells, and how they mediate their function. Here we demonstrate, using yeast two
hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling
analysis (DCA), RNA-sequencing, ROS and iron imaging, and single and double shRNA
lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1
directly interact in mammalian cells and could function in the same cellular
pathway. We further show using an in vitro cluster transfer assay that mNT can
transfer its clusters to NAF-1. Our study highlights the possibility that mNT and
NAF-1 function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the
levels of iron and Fe-S clusters under control in the mitochondria of mammalian
cells, thereby preventing the activation of apoptosis and/or autophagy and
supporting cellular proliferation.
PMID- 28426723
TI - A decade of arboviral activity-Lessons learned from the trenches.
PMID- 28426724
TI - Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the
Pacific oyster and in silico binding to environmental chemicals.
AB - Disruption of nuclear receptors, a transcription factor superfamily regulating
gene expression in animals, is one proposed mechanism through which pollution
causes effects in aquatic invertebrates. Environmental pollutants have the
ability to interfere with the receptor's functions through direct binding and
inducing incorrect signals. Limited knowledge of invertebrate endocrinology and
molecular regulatory mechanisms, however, impede the understanding of endocrine
disruptive effects in many aquatic invertebrate species. Here, we isolated three
nuclear receptors of the Pacific oyster, Crassostrea gigas: two isoforms of the
retinoid X receptor, CgRXR-1 and CgRXR-2, a retinoic acid receptor ortholog
CgRAR, and a peroxisome proliferator-activated receptor ortholog CgPPAR. Computer
modelling of the receptors based on 3D crystal structures of human proteins was
used to predict each receptor's ability to bind to different ligands in silico.
CgRXR showed high potential to bind and be activated by 9-cis retinoic acid and
the organotin tributyltin (TBT). Computer modelling of CgRAR revealed six
residues in the ligand binding domain, which prevent the successful interaction
with natural and synthetic retinoid ligands. This supports an existing theory of
loss of retinoid binding in molluscan RARs. Modelling of CgPPAR was less reliable
due to high discrepancies in sequence to its human ortholog. Yet, there are
suggestions of binding to TBT, but not to rosiglitazone. The effect of potential
receptor ligands on early oyster development was assessed after 24h of chemical
exposure. TBT oxide (0.2MUg/l), all-trans retinoic acid (ATRA) (0.06 mg/L) and
perfluorooctanoic acid (20 mg/L) showed high effects on development (>74%
abnormal developed D-shelled larvae), while rosiglitazone (40 mg/L) showed no
effect. The results are discussed in relation to a putative direct (TBT)
disruption effect on nuclear receptors. The inability of direct binding of ATRA
to CgRAR suggests either a disruptive effect through a pathway excluding nuclear
receptors or an indirect interaction. Our findings provide valuable information
on potential mechanisms of molluscan nuclear receptors and the effects of
environmental pollution on aquatic invertebrates.
PMID- 28426725
TI - Dynamic regulation of Pin1 expression and function during zebrafish development.
AB - The prolyl isomerase Pin1 plays a key role in the modulation of proline-directed
phosphorylation signaling by inducing local conformational changes in
phosphorylated protein substrates. Extensive studies showed different roles for
Pin1 in physiological processes and pathological conditions such as cancer and
neurodegenerative diseases. However, there are still several unanswered questions
regarding its biological role. Notably, despite evidences from cultured cells
showing that Pin1 expression and activity may be regulated by different
mechanisms, little is known on their relevance in vivo. Using Danio rerio
(zebrafish) as a vertebrate model organism we showed that pin1 expression is
regulated during embryogenesis to achieve specific mRNA and protein distribution
patterns. Moreover, we found different subcellular distribution in particular
stages and cell types and we extended the study of Pin1 expression to the adult
zebrafish brain. The analysis of Pin1 overexpression showed alterations on
zebrafish development and the presence of p53-dependent apoptosis. Collectively,
our results suggest that specific mechanisms are operated in different cell types
to regulate Pin1 function.
PMID- 28426726
TI - Vibrotactile stimulation: A non-pharmacological intervention for opioid-exposed
newborns.
AB - OBJECTIVE: To examine the therapeutic potential of stochastic vibrotactile
stimulation (SVS) as a complementary non-pharmacological intervention for
withdrawal in opioid-exposed newborns. STUDY DESIGN: A prospective, within
subjects single-center study was conducted in 26 opioid-exposed newborns (>37
weeks; 16 male) hospitalized since birth and treated pharmacologically for
Neonatal Abstinence Syndrome. A specially-constructed mattress delivered low
level SVS (30-60Hz, 10-12MUm RMS), alternated in 30-min intervals between
continuous vibration (ON) and no vibration (OFF) over a 6-8 hr session. Movement
activity, heart rate, respiratory rate, axillary temperature and blood-oxygen
saturation were calculated separately for ON and OFF. RESULTS: There was a 35%
reduction in movement activity with SVS (p<0.001), with significantly fewer
movement periods >30 sec duration for ON than OFF (p = 0.003). Incidents of
tachypneic breaths and tachycardic heart beats were each significantly reduced
with SVS, whereas incidents of eupneic breaths and eucardic heart beats each
significantly increased with SVS (p<0.03). Infants maintained body temperature
and arterial-blood oxygen level independent of stimulation condition.
CONCLUSIONS: SVS reduced hyperirritability and pathophysiological instabilities
commonly observed in pharmacologically-managed opioid-exposed newborns. SVS may
provide an effective complementary therapeutic intervention for improving
autonomic function in newborns with Neonatal Abstinence Syndrome.
PMID- 28426727
TI - CD4 T-cell expression of IFN-gamma and IL-17 in pediatric malarial anemia.
AB - In Plasmodium falciparum holoendemic transmission regions of western Kenya, life
threatening pediatric malaria manifests primarily as severe malarial anemia (SMA,
Hb<=6.0 g/dL with any density parasitemia). To determine the role that CD4+ T
cell-driven inflammatory responses have in the pathogenesis of SMA, peripheral
CD4+ T-cell populations and their intracellular production of pro-inflammatory
cytokines (IFN-gamma and IL-17) were characterized in children aged 12-36 months
of age stratified into two groups: non-severe malarial anemia (non-SMA, Hb>=6.0
g/dL, n = 50) and SMA (n = 39). In addition, circulating IFN-gamma and IL-17 were
measured as part of a Cytokine 25-plex Antibody Bead Kit, Human (BioSourceTM
International). Children with SMA had higher overall proportions of circulating
lymphocytes (P = 0.003) and elevated proportions of lymphocytes expressing IFN
gamma (P = 0.014) and comparable IL-17 (P = 0.101). In addition, SMA was
characterized by decreased memory-like T-cells (CD4+CD45RA-) expressing IL-17 (P
= 0.009) and lower mean fluorescence intensity in memory-like CD4+ T-cells for
both IFN-gamma (P = 0.063) and IL-17 (P = 0.006). Circulating concentrations of
IFN-gamma were higher in children with SMA (P = 0.009), while IL-17 levels were
comparable between the groups (P = 0.164). Furthermore, circulating levels of IFN
gamma were negatively correlated with IL-17 levels in both groups of children
(SMA: r = -0.610, P = 0.007; and non-SMA: r = -0.516, P = 0.001), while
production of both cytokines by lymphocytes were positively correlated (SMA: r =
0.349, P = 0.037; and non-SMA: r = 0.475, P = 0.001). In addition, this
correlation was only maintained by the memory-like CD4+ T cells (r = 0.365, P =
0.002) but not the naive-like CD4+ T cells. However, circulating levels of IFN
gamma were only associated with naive-like CD4+ T cells producing IFN-gamma (r =
0.547, P = 0.028), while circulating levels of IL-17 were not associated with any
of the cell populations. Taken together, these results suggest that enhanced
severity of malarial anemia is associated with higher overall levels of
circulating lymphocytes, enhanced intracellular production of IFN-gamma by
peripheral lymphocytes and high circulating IFN-gamma levels. In addition, the
observed inverse relationship between the circulating levels of IFN-gamma and IL
17 together with the reduction in the levels of memory-like CD4+ T cells
expressing IL-17 in children with SMA may suggest possible relocation of these
cells in the deeper tissues for their pathological effect.
PMID- 28426728
TI - Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The
MESA Lung Study.
AB - BACKGROUND: Evaluation of impaired left ventricular (LV) filling has focused on
intrinsic causes of LV dysfunction; however, pulmonary vascular changes may
contribute to reduced LV filling and dyspnea. We hypothesized that lower total
pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated
with dyspnea and decrements in LV end-diastolic volume, particularly among ever
smokers. METHODS: The Multi-Ethnic Study of Atherosclerosis recruited adults
without clinical cardiovascular disease in 2000-02. In 2010-12, TPVV was
ascertained as the volume of arteries and veins in the lungs detectable on non
contrast chest CT (vessels >=1 mm diameter). Cardiac measures were assessed by
magnetic resonance imaging (MRI). Dyspnea was self-reported. RESULTS: Of 2303
participants, 53% had ever smoked cigarettes. Among ever-smokers, a lower TPVV
was associated with a lower LV end-diastolic volume (6.9 mL per SD TPVV), stroke
volume, and cardiac output and with dyspnea (all P-values <0.001). Findings were
similar among those without lung disease and those with 0-10 pack-years but were
mostly non-significant among never-smokers. TPVV was associated smaller left
atrial volume but not with LV ejection fraction or MRI measures of impaired LV
relaxation. In a second sample of ever-smokers, a lower pulmonary microvascular
blood volume on contrast-enhanced MRI was also associated with a lower LV end
diastolic volume (P-value = 0.008). CONCLUSION: Reductions in pulmonary vascular
volume were associated with lower LV filling and dyspnea among ever-smokers,
including those without lung disease, suggesting that smoking-related pulmonary
vascular changes may contribute to symptoms and impair cardiac filling and
function without evidence of impaired LV relaxation.
PMID- 28426729
TI - Cultural differences in room size perception.
AB - Cultural differences in spatial perception have been little investigated, which
gives rise to the impression that spatial cognitive processes might be universal.
Contrary to this idea, we demonstrate cultural differences in spatial volume
perception of computer generated rooms between Germans and South Koreans. We used
a psychophysical task in which participants had to judge whether a rectangular
room was larger or smaller than a square room of reference. We systematically
varied the room rectangularity (depth to width aspect ratio) and the viewpoint
(middle of the short wall vs. long wall) from which the room was viewed. South
Koreans were significantly less biased by room rectangularity and viewpoint than
their German counterparts. These results are in line with previous notions of
general cognitive processing strategies being more context dependent in East
Asian societies than Western ones. We point to the necessity of considering
culturally-specific cognitive processing strategies in visual spatial cognition
research.
PMID- 28426730
TI - Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is
associated with hepatocellular carcinoma risk.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been
identified as a tumor suppressor gene in multiple cancers. We hypothesize that
genetic variations in WWOX are associated with HCC risk. METHODOLOGY/PRINCIPAL
FINDINGS: Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were
evaluated from 708 normal controls and 354 patients with HCC. We identified a
significant association between a WWOX single nucleotide polymorphism (SNP),
rs73569323, and decreased risk of HCC. After adjustment for potential
confounders, patients with at least one T allele at rs11545028 of WWOX may have a
significantly smaller tumor size, reduced levels of alpha-fetoprotein and alanine
aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX
conferred higher risk of vascular invasion. Additional in silico analysis also
suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which
in turn contributes to tumor vascular invasion. CONCLUSIONS: In conclusion,
genetic variations in WWOX may be a significant predictor of early HCC occurrence
and a reliable biomarker for disease progression.
PMID- 28426731
TI - Effect of genetic variation in microRNA binding site in WNT1-inducible signaling
pathway protein 1 gene on oral squamous cell carcinoma susceptibility.
AB - BACKGROUND: Oral squamous cell carcinoma (OSCC), which is the most common head
and neck cancer, accounts for 1%-2% of all human malignancies and is
characterized by poor prognosis and reduced survival rates. WNT1-inducible
signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the
Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental
functions and may be involved in carcinogenesis. This study investigated WISP1
single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and
clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Real-time
polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC
patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970
polymorphism carriers with at least one G allele were susceptible to OSCC.
Moreover, compared with smokers, non-smoker patients with higher frequencies of
WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a
large tumor size. In addition, OSCC patients who were betel quid chewers and
carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node
metastasis. CONCLUSION: Our results demonstrate that a joint effect of WISP1
rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing
causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a
marker or a therapeutic target in OSCC.
PMID- 28426732
TI - Regulation of SESAME-mediated H3T11 phosphorylation by glycolytic enzymes and
metabolites.
AB - Cancer cells prefer aerobic glycolysis, but little is known about the underlying
mechanism. Recent studies showed that the rate-limiting glycolytic enzymes,
pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to
regulate gene expression and cell proliferation, revealing its non-metabolic
functions in connecting glycolysis and histone modifications. We have reported
that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene
expression and oxidative stress resistance. But how glycolysis regulates H3T11
phosphorylation remains unclear. Here, using a series of glycolytic enzyme
mutants and commercial available metabolites, we investigated the role of
glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of
glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2),
triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3)
significantly reduced H3T11 phosphorylation. Further study demonstrated that
glycolysis regulates H3T11 phosphorylation by fueling the substrate,
phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide
a comprehensive view of how glycolysis modulates H3T11 phosphorylation.
PMID- 28426734
TI - Study of deaths by suicide of homosexual prisoners in Nazi Sachsenhausen
concentration camp.
AB - Living conditions in Nazi concentration camps were harsh and inhumane, leading
many prisoners to commit suicide. Sachsenhausen (Oranienburg, Germany) was a
concentration camp that operated from 1936 to 1945. More than 200,000 people were
detained there under Nazi rule. This study analyzes deaths classified as suicides
by inmates in this camp, classified as homosexuals, both according to the
surviving Nazi files. This collective was especially repressed by the Nazi
authorities. Data was collected from the archives of Sachsenhausen Memorial and
the International Tracing Service in Bad Arolsen. Original death certificates and
autopsy reports were reviewed. Until the end of World War II, there are 14 death
certificates which state "suicide" as cause of death of prisoners classified as
homosexuals, all of them men aged between 23 and 59 years and of various
religions and social strata. Based on a population of 1,200 prisoners classified
as homosexuals, this allows us to calculate a suicide rate of 1,167/100,000 (over
the period of eight years) for this population, a rate 10 times higher than for
global inmates (111/100,000). However, our study has several limitations: not all
suicides are registered; some murders were covered-up as suicides; most documents
were lost during the war or destroyed by the Nazis when leaving the camps and not
much data is available from other camps to compare. We conclude that committing
suicides in Sachsenhausen was a common practice, although accurate data may be
impossible to obtain.
PMID- 28426733
TI - Mini-G proteins: Novel tools for studying GPCRs in their active conformation.
AB - Mini-G proteins are the engineered GTPase domains of Galpha subunits. They couple
to GPCRs and recapitulate the increase in agonist affinity observed upon coupling
of a native heterotrimeric G protein. Given the small size and stability of mini
G proteins, and their ease of expression and purification, they are ideal for
biophysical studies of GPCRs in their fully active state. The first mini-G
protein developed was mini-Gs. Here we extend the family of mini-G proteins to
include mini-Golf, mini-Gi1, mini-Go1 and the chimeras mini-Gs/q and mini-Gs/i.
The mini-G proteins were shown to couple to relevant GPCRs and to form stable
complexes with purified receptors that could be purified by size exclusion
chromatography. Agonist-bound GPCRs coupled to a mini-G protein showed higher
thermal stability compared to the agonist-bound receptor alone. Fusion of GFP at
the N-terminus of mini-G proteins allowed receptor coupling to be monitored by
fluorescence-detection size exclusion chromatography (FSEC) and, in a separate
assay, the affinity of mini-G protein binding to detergent-solubilised receptors
was determined. This work provides the foundation for the development of any mini
G protein and, ultimately, for the structure determination of GPCRs in a fully
active state.
PMID- 28426735
TI - Ten years of Chagas disease research: Looking back to achievements, looking ahead
to challenges.
PMID- 28426736
TI - Lacanobia oleracea nucleopolyhedrovirus (LaolNPV): A new European species of
alphabaculovirus with a narrow host range.
AB - During an insect sampling program in alfalfa crops near Montpellier, France in
2011, Lacanobia oleracea larvae were collected that died due to
nucleopolyhedrovirus infection (LaolNPV). This virus was subjected to molecular
and biological characterization. The virus was a multiple nucleocapsid NPV that
showed similar restriction profiles to Mamestra configurata NPV-A (MacoNPV-A) but
with significant differences. Polypeptide analysis demonstrated similar proteins
in occlusion bodies and occlusion derived virions, to those observed in NPVs from
Mamestra spp. Terminal sequencing revealed that the genome organization shared
similarity with that of MacoNPV-A. The most homologous virus was MacoNPV-A 90/2
isolate (95.63% identity and 96.47% similarity), followed by MacoNPV-A 90/4
strain (95.37% and 96.26%), MacoNPV-B (89.21% and 93.53%) and M. brassicae MNPV
(89.42% and 93.74%). Phylogenetic analysis performed with lef-8, lef-9, polh and
a concatenated set of genes showed that LaolNPV and the Mamestra spp. NPVs
clustered together with HaMNPV, but with a closer genetic distance to MacoNPV-A
strains. The Kimura 2-parameter (K-2-P) distances of the complete genes were
greater than 0.05 between LaolNPV and the MbMNPV/MacoNPV-B/HaMNPV complex, which
indicates that LaolNPV is a distinct species. K-2-P distances were in the range
0.015-0.050 for comparisons of LaolNPV with MacoNPV-A strains, such that
additional biological characteristics should be evaluated to determine species
status. While MacoNPV-A was pathogenic to seven lepidopteran species tested,
LaolNPV was only pathogenic to Chrysodeixis chalcites. Given these findings,
Lacanobia oleracea nucleopolyhedrovirus should be considered as a new species in
the Alphabaculovirus genus.
PMID- 28426737
TI - Incidence and predictors of excessive warfarin anticoagulation in patients with
atrial fibrillation-The EWA study.
AB - Vitamin K antagonist warfarin is widely used in clinical practice and excessive
anticoagulation is a well-known complication of this therapy. Little is known
about permanent and temporary predictors for severe overanticoagulation. The aim
of this study was to investigate the occurrence and predicting factors for
episodes with very high (>=9) international normalized ratio (INR) values in
warfarin treated patients with atrial fibrillation (AF). Excessive Warfarin
Anticoagulation (EWA) study screened all patients (n = 13618) in the Turku
University Hospital region with an INR >=2 between years 2003-2015. Patients
using warfarin anticoagulation for AF with very high (>=9) INR values (EWA Group)
were identified (n = 412 patients) and their characteristics were compared to a
control group (n = 405) of AF patients with stable INR during long-term follow
up. Over 20% (n = 92) of the EWA patients had more than one event of very high
INR and in 105 (25.5%) patients EWA led to a bleeding event. Of the several
temporary and permanent EWA risk factors observed, strongest were excessive
alcohol consumption in 9.6% of patients (OR 24.4, 95% CI 9.9-50.4, p<0.0001) and
reduced renal function (OR 15.2, 95% CI 5.67-40.7, p<0.0001). Recent antibiotic
or antifungal medication, recent hospitalization or outpatient clinic visit and
the first 6 months of warfarin use were the most significant temporary risk
factors for EWA. Excessive warfarin anticoagulation can be predicted with several
permanent and temporary clinical risk factors, many of which are modifiable.
PMID- 28426738
TI - Is antiplatelet treatment effective at attenuating the progression of white
matter hyperintensities?
AB - OBJECTIVE: We performed this study to assess the effect of an antiplatelet agent
on the progression of white matter hyperintensities (WMH). METHODS: From August
2003 to May 2005, we consecutively enrolled patients who underwent brain magnetic
resonance imaging (MRI) for health check-up purposes and showed no significant
findings other than WMH of any degree. Patients were divided into two groups
based on whether or not they received antiplatelet therapy. All patients had a
follow-up brain MRI after 5 years and WMH volume change was measured using
imaging analysis software. To minimize selection bias potentially arising from
antiplatelet treatment assignment, analyses were inverse probability weighted.
RESULTS: Among the 93 patients who met the inclusion criteria, 54 patients
(58.1%) were grouped as the antiplatelet group (AG), and the remaining 39
patients (41.9%) as the non-antiplatelet group (NAG). After inverse propensity
weighting, all baseline characteristics were similar between the two groups, and
antiplatelet treatment did not show any significant effect on the total WMH
volume change (p = 0.957). CONCLUSION: Antiplatelet medication may not alter the
progression of WMH.
PMID- 28426739
TI - Artificial neural network and SARIMA based models for power load forecasting in
Turkish electricity market.
AB - Load information plays an important role in deregulated electricity markets,
since it is the primary factor to make critical decisions on production planning,
day-to-day operations, unit commitment and economic dispatch. Being able to
predict the load for a short term, which covers one hour to a few days, equips
power generation facilities and traders with an advantage. With the deregulation
of electricity markets, a variety of short term load forecasting models are
developed. Deregulation in Turkish Electricity Market has started in 2001 and
liberalization is still in progress with rules being effective in its predefined
schedule. However, there is a very limited number of studies for Turkish Market.
In this study, we introduce two different models for current Turkish Market using
Seasonal Autoregressive Integrated Moving Average (SARIMA) and Artificial Neural
Network (ANN) and present their comparative performances. Building models that
cope with the dynamic nature of deregulated market and are able to run in real
time is the main contribution of this study. We also use our ANN based model to
evaluate the effect of several factors, which are claimed to have effect on
electrical load.
PMID- 28426740
TI - Uncovering the molecular and physiological processes of anticancer leads binding
human serum albumin: A physical insight into drug efficacy.
AB - Human serum albumin (HSA) has its ability to bind drug molecules and influence
their efficacies. Although anticancer leads NSC48693 and NSC290956 functioned at
the same mechanism, the drug efficacies were obviously distinct. To gain insight
into the distinct drug efficacy, the molecular and physiological processes of
anticancer leads binding HSA have been investigated via a combined experimental
and theoretical approach. The binding site, as characterized by fluorescence
quenching and molecular modeling, is found to be located at site II in subdomain
III A for NSC48693 with tight binding and at site FA1 in subdomain I B for
NSC290956 with negatively cooperative binding, respectively. As indicated by the
thermodynamic analysis, NSC48693 binds to HSA with an enthalpy driven mechanism,
while NSC290956 binding with HSA is entropically driven. The further kinetic
analysis indicates that the association rates appear to be similar to these two
anticancer leads, however, the dissociation rate of NSC48693 is approximately 5
fold slower than that of NSC290956. For NSC48693, the pharmacodynamic efficacy is
less than that of NSC290956, while its pharmacokinetic behavior is better than
that of NSC290956. These parameters influence the pharmacodynamic efficacy and
pharmacokinetic behavior, which will give further impacts on drug efficacy in
vivo.
PMID- 28426741
TI - AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal
gene transfers from bacteria to eukaryotes.
AB - Organisms have evolved the ability to tolerate toxic substances in their
environments, often by producing metabolic enzymes that efficiently detoxify the
toxicant. Inorganic arsenic is one of the most toxic and carcinogenic substances
in the environment, but many organisms, including humans, metabolise inorganic
arsenic to less toxic metabolites. This multistep process produces mono-, di-,
and trimethylated arsenic metabolites, which the organism excretes. In humans,
arsenite methyltransferase (AS3MT) appears to be the main metabolic enzyme that
methylates arsenic. In this study, we examined the evolutionary origin of AS3MT
and assessed the ability of different genotypes to produce methylated arsenic
metabolites. Phylogenetic analysis suggests that multiple, independent horizontal
gene transfers between different bacteria, and from bacteria to eukaryotes,
increased tolerance to environmental arsenic during evolution. These findings are
supported by the observation that genetic variation in AS3MT correlates with the
capacity to methylate arsenic. Adaptation to arsenic thus serves as a model for
how organisms evolve to survive under toxic conditions.
PMID- 28426742
TI - Multiple components of PKA and TGF-beta pathways are mutated in pseudomyxoma
peritonei.
AB - Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly
restricted to the peritoneal cavity and most commonly originating from the
appendix. The genetic background of PMP is poorly understood and no targeted
treatments are currently available for this fatal disease. While RAS signaling
pathway is affected in most if not all PMP cases and over half of them also have
a mutation in the GNAS gene, other genetic alterations and affected pathways are,
to a large degree, poorly known. In this study, we sequenced whole coding genome
of nine PMP tumors and paired normal tissues in order to identify additional,
commonly mutated genes and signaling pathways affected in PMP. These exome
sequencing results were validated with an ultra-deep amplicon sequencing method,
leading to 14 validated variants. The validated results contain seven genes that
contribute to the protein kinase A (PKA) pathway. PKA pathway, which also
contains GNAS, is a major player of overproduction of mucin, which is the
characteristic feature of PMP. In addition to PKA pathway, we identified
mutations in six genes that belong to the transforming growth factor beta (TGF
beta) pathway, which is a key regulator of cell proliferation. Since either GNAS
mutation or an alternative mutation in the PKA pathway was identified in 8/9
patients, inhibition of the PKA pathway might reduce mucin production in most of
the PMP patients and potentially suppress disease progression.
PMID- 28426743
TI - Acute kidney injury can predict in-hospital and long-term mortality in elderly
patients undergoing hip fracture surgery.
AB - BACKGROUND: Hip fracture is a common health problem in the elderly that is
associated with increased mortality. Acute kidney injury (AKI) is a frequent
complication in elderly patients undergoing surgery and is associated with the
clinical outcome. We evaluated the incidence and risk factors of AKI in elderly
patients undergoing hip fracture surgery and the impact of AKI on short- and long
term clinical outcomes. METHODS: We performed a retrospective cohort study of 450
elderly patients who underwent hip fracture surgery between January 2010 and
December 2012. We defined AKI according to the Acute Kidney Injury Network (AKIN)
criteria and investigated the effect of AKI on the duration of hospital stay and
in-hospital and long-term mortality. RESULTS: Of the 450 patients, 95 (21.1%)
developed AKI during hospitalization and 178 (39.6%) died, with a mean follow-up
of 3.6 +/- 1.0 years. The baseline serum creatinine level, use of angiotensin
converting enzyme inhibitors or angiotensin-II receptor antagonists, red blood
cell transfusion volume, and history of coronary artery disease were independent
risk factors for AKI. Patients with AKI during hospitalization had significantly
longer hospital stays and higher in-hospital and long-term mortality than those
without AKI. Multivariate analysis revealed that age, history of coronary artery
disease, serum albumin level, and AKI were independent predictors of long-term
mortality. CONCLUSIONS: AKI is a frequent complication in elderly patients
undergoing hip fracture surgery and is independently associated with increased in
hospital and long-term mortality.
PMID- 28426744
TI - Pharmacokinetics and relative bioavailability of an oral amoxicillin-apramycin
combination in pigs.
AB - A new compound granular premix of amoxicillin (20% w/w dry mass)/apramycin (5%
w/w dry mass) was developed, and its pharmacokinetics and relative
bioavailability were determined in pigs following oral administration following a
cross-over study design. The pharmacokinetic parameters of amoxicillin
(t1/2lambda = 6.43 +/- 4.85h, Cmax = 3.2 +/- 1.35 MUg.mL-1, Tmax = 1.92 +/- 0.58,
AUCINF = 8.98 +/- 2.11 h.MUg.mL-1) and apramycin (t1/2lambda = 8.67+/-4.4h, Cmax
= 0.23 +/- 0.12 MUg.mL-1, Tmax = 2.25 +/- 0.82 h, AUCINF = 12.37 +/- 8.64h.MUg.mL
1) when administered as the amoxicillin-apramycin granular premix did not
significantly differ from those for the single-ingredient powder form of each
component. The relative bioavailability of amoxicillin following oral
administration of the amoxicillin-apramycin granular premix was 22.62% when
compared to the intramuscular administration of commercial amoxicillin sodium
powder. This is the first report of a new amoxicillin-apramycin combination which
has a potential veterinary application the for prevention and treatment digestive
tract infections in pigs.
PMID- 28426745
TI - Objective classification of zonular weakness based on lens movement at the start
of capsulorhexis.
AB - PURPOSE: To quantify zonular weakness based on lens movement at the start of
continuous curvilinear capsulorhexis (CCC) and establish a classification system
for it. SETTING: Kozawa Eye Hospital and Diabetes Center, Mito, Japan. DESIGN:
Retrospective interventional case series. METHODS: We examined 402 consecutive
eyes of 316 patients who underwent CCC, phacoemulsification and aspiration (PEA),
and intraocular lens (IOL) implantation. The movement of the lens capsule was
measured using images from video recordings of the CCC procedure. Zonular
weakness was classified based on the shifted distance: Grade I, less than 0.20
mm; Grade II, 0.20-0.39 mm; and Grade III, greater than 0.40 mm. For each of
these grades, we examined the use of the capsule stabilization device during PEA,
the surgical procedure for lens removal, and IOL fixation. RESULTS: We classified
276 eyes (68.6%) as Grade I, 102 eyes (25.4%) as Grade II, and 24 eyes (6.0%) as
Grade III. As the grade increased, the use of the capsule stabilization device in
PEA and scleral suture fixation of IOL increased. CONCLUSIONS: Zonular weakness
was quantified by measuring the movement of the lens capsule. An objective
classification of zonular weakness based on lens movement may be useful for
selecting the appropriate device and procedure during cataract surgery.
PMID- 28426746
TI - Low levels of Cd induce persisting epigenetic modifications and acclimation
mechanisms in the earthworm Lumbricus terrestris.
AB - Toxic effects of cadmium (Cd), a common soil pollutant, are still not very well
understood, particularly in regard to its epigenetic impact. Therefore, the aim
of this study was to assess DNA methylation changes and their persistence in the
earthworm Lumbricus terrestris upon chronic low dose Cd exposure using
methylation sensitive amplification polymorphism (MSAP). Moreover, the biomarker
response and fitness of the earthworms, as well as the expression of
detoxification-related genes (metallothionein (MT) and phytochelatin synthase
(PCS)) was evaluated. Low levels of Cd caused an increase in genome-wide DNA
methylation, which remained partly modified, even after several months of
recovery in unpolluted soil. Increased cellular stress seemed to decrease after
two weeks of exposure whereas fitness parameters remained unaffected by Cd,
probably as a result from the activation of detoxification mechanisms like the
expression of MTs. Interestingly, even though the level of Cd exposure was very
low, MT expression levels indicate the development of acclimation mechanisms.
Taken together, this study demonstrates that acclimation, as well as epigenetic
modifications can occur already in moderately polluted environments. In addition,
these effects can have long-lasting impacts on key species of soil invertebrates
and might persist long after the actual heavy metal challenge has passed.
PMID- 28426748
TI - Tails of the Travelling Gaussian model and the relative age effect: Tales of age
discrimination and wasted talent.
AB - The Relative Age Effect (RAE) documents the inherent disadvantages of being
younger rather than older in an age-banded cohort, typically a school- or
competition-year, to the detriment of career-progression, earnings and wellbeing
into adulthood. We develop the Tails of the Travelling Gaussian (TTG) to model
the mechanisms behind RAE. TTG has notable advantages over existing approaches,
which have been largely descriptive, potentially confounded, and non-comparable
across contexts. In Study 1, using data from the UK's Millennium Cohort Study, we
investigate the different levels of RAE bias across school-level academic
subjects and "personality" traits. Study 2 concerns biased admissions to elite
English Premier League soccer academies, and shows the model can still be used
with minimal data. We also develop two practical metrics: the discrimination
index (ID), to quantify the disadvantages facing cohort-younger children; and the
wastage metric (W), to quantify the loss through untapped potential. TTG is
sufficiently well-specified to simulate the consequences of ID and W for policy
change.
PMID- 28426747
TI - Metabolic analysis of radioresistant medulloblastoma stem-like clones and
potential therapeutic targets.
AB - Medulloblastoma is a fatal brain tumor in children, primarily due to the presence
of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway
is a potential target of cancer therapy because it is often different between
cancer cells and normal cells. However, the metabolic properties of
medulloblastoma stem cells, and whether specific metabolic pathways are essential
for sustaining their stem cell-like phenotype and radioresistance, remain
unclear. We have established radioresistant medulloblastoma stem-like clones
(rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we
assessed reactive oxygen species (ROS) production, mitochondria function, oxygen
consumption rate (OCR), energy state, and metabolites of glycolysis and
tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher
lactate production and lower oxygen consumption rate than parental cells.
Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production,
and existed in a low-energy state. Treatment with the metabolic modifier
dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis
inhibition, elongated mitochondria morphology, and increased ROS production. DCA
also increased radiosensitivity by suppression of the DNA repair capacity through
nuclear oxidization and accelerated the generation of acetyl CoA to compensate
for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like
characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs.
Together, our findings provide insights into the specific metabolism of rMSLCs
and illuminate potential metabolic targets that might be exploited for
therapeutic benefit in medulloblastoma.
PMID- 28426749
TI - Molecular characterization, tissue tropism, and genetic variability of the novel
Mupapillomavirus type HPV204 and phylogenetically related types HPV1 and HPV63.
AB - HPV204 is the only newly identified Mupapillomavirus (Mu-PV) type in more than a
decade. To comprehensively characterize HPV204, we performed a detailed molecular
analysis of the viral genome and evaluated its clinical relevance in comparison
to the other Mu-PVs, HPV1 and HPV63. The 7,227-bp long genome of HPV204 exhibits
typical genomic organization of Mu-PVs with eight open reading frames (ORFs) (E6,
E7, E1, E2, E8, E4, L2, and L1). We developed three type-specific quantitative
real-time PCRs and used them to test a representative collection (n = 1,006) of
various HPV-associated benign and malignant neoplasms, as well as samples of
clinically normal cutaneous, mucosal, and mucocutaneous origins. HPV204, HPV1,
and HPV63 were detected in 1.1%, 2.7%, and 1.9% of samples tested, respectively,
and were present in skin and mucosa, suggesting dual tissue tropism of all Mu
PVs. To evaluate the etiological role of Mu-PVs in the development of HPV
associated neoplasms, Mu-PV viral loads per single cell were estimated. HPV1 and
HPV63 were present in high viral copy numbers in 3/43 and 1/43 cutaneous warts,
respectively, and were identified as the most likely causative agents of these
warts. HPV204 viral load was extremely low in a single HPV204-positive cutaneous
wart (7.4 * 10-7 viral copies/cell). Hence, etiological association between
HPV204 and the development of cutaneous warts could not be established. To the
best of our knowledge, this is the first study to evaluate the genetic
variability of Mu-PVs by sequencing complete LCR genomic regions of HPV204, HPV1,
and HPV63. We detected several nucleotide substitutions and deletions within the
LCR genomic regions of Mu-PVs and identified two genetic variants of HPV204 and
HPV63 and five genetic variants of HPV1.
PMID- 28426750
TI - Partnering to promote research where it matters.
PMID- 28426751
TI - The role of microsporidian polar tube protein 4 (PTP4) in host cell infection.
AB - Microsporidia have been identified as pathogens that have important effects on
our health, food security and economy. A key to the success of these obligate
intracellular pathogens is their unique invasion organelle, the polar tube, which
delivers the nucleus containing sporoplasm into host cells during invasion. Due
to the size of the polar tube, the rapidity of polar tube discharge and
sporoplasm passage, and the absence of genetic techniques for the manipulation of
microsporidia, study of this organelle has been difficult and there is relatively
little known regarding polar tube formation and the function of the proteins
making up this structure. Herein, we have characterized polar tube protein 4
(PTP4) from the microsporidium Encephalitozoon hellem and found that a monoclonal
antibody to PTP4 labels the tip of the polar tube suggesting that PTP4 might be
involved in a direct interaction with host cell proteins during invasion. Further
analyses employing indirect immunofluorescence (IFA), enzyme-linked immunosorbent
(ELISA) and fluorescence-activated cell sorting (FACS) assays confirmed that PTP4
binds to mammalian cells. The addition of either recombinant PTP4 protein or anti
PTP4 antibody reduced microsporidian infection of its host cells in vitro.
Proteomic analysis of PTP4 bound to host cell membranes purified by
immunoprecipitation identified transferrin receptor 1 (TfR1) as a potential host
cell interacting partner for PTP4. Additional experiments revealed that knocking
out TfR1, adding TfR1 recombinant protein into cell culture, or adding anti-TfR1
antibody into cell culture significantly reduced microsporidian infection rates.
These results indicate that PTP4 is an important protein competent of the polar
tube involved in the mechanism of host cell infection utilized by these
pathogens.
PMID- 28426753
TI - Correction: A MultiSite Gateway Toolkit for Rapid Cloning of Vertebrate
Expression Constructs with Diverse Research Applications.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159277.].
PMID- 28426752
TI - Somatic copy number alterations in gastric adenocarcinomas among Asian and
Western patients.
AB - Gastric cancer, a leading worldwide cause of cancer mortality, shows high
geographic and ethnic variation in incidence rates, which are highest in East
Asia. The anatomic locations and clinical behavior also differ by geography,
leading to the controversial idea that Eastern and Western forms of the disease
are distinct. In view of these differences, we investigated whether gastric
cancers from Eastern and Western patients show distinct genomic profiles. We used
high-density profiling of somatic copy-number aberrations to analyze the largest
collection to date of gastric adenocarcinomas and utilized genotyping data to
rigorously annotate ethnic status. The size of this collection allowed us to
accurately identify regions of significant copy-number alteration and separately
to evaluate tumors arising in Eastern and Western patients. Among molecular
subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers
showing chromosomal instability was modestly higher in Western patients. After
accounting for this difference, however, gastric cancers arising in Easterners
and Westerners have highly similar somatic copy-number patterns. Only one genomic
event, focal deletion of the phosphatase gene PTPRD, was significantly enriched
in Western cases, though also detected in Eastern cases. Thus, despite the
different risk factors and clinical features, gastric cancer appears to be a
fundamentally similar disease in both populations and the divergent clinical
outcomes cannot be ascribed to different underlying structural somatic genetic
aberrations.
PMID- 28426754
TI - Assessing environmental attributes and effects of climate change on Sphagnum
peatland distributions in North America using single- and multi-species models.
AB - The fate of Northern peatlands under climate change is important because of their
contribution to global carbon (C) storage. Peatlands are maintained via greater
plant productivity (especially of Sphagnum species) than decomposition, and the
processes involved are strongly mediated by climate. Although some studies
predict that warming will relax constraints on decomposition, leading to
decreased C sequestration, others predict increases in productivity and thus
increases in C sequestration. We explored the lack of congruence between these
predictions using single-species and integrated species distribution models as
proxies for understanding the environmental correlates of North American Sphagnum
peatland occurrence and how projected changes to the environment might influence
these peatlands under climate change. Using Maximum entropy and BIOMOD modelling
platforms, we generated single and integrated species distribution models for
four common Sphagnum species in North America under current climate and a 2050
climate scenario projected by three general circulation models. We evaluated the
environmental correlates of the models and explored the disparities in niche
breadth, niche overlap, and climate suitability among current and future models.
The models consistently show that Sphagnum peatland distribution is influenced by
the balance between soil moisture deficit and temperature of the driest quarter
year. The models identify the east and west coasts of North America as the core
climate space for Sphagnum peatland distribution. The models show that, at least
in the immediate future, the area of suitable climate for Sphagnum peatland could
expand. This result suggests that projected warming would be balanced effectively
by the anticipated increase in precipitation, which would increase Sphagnum
productivity.
PMID- 28426755
TI - Correction: Limbic-thalamo-cortical projections and reward-related circuitry
integrity affects eating behavior: A longitudinal DTI study in adolescents with
restrictive eating disorders.
AB - [This corrects the article DOI: 10.1371/journal.pone.0172129.].
PMID- 28426757
TI - Correction: Community ART Support Groups in Mozambique: The Potential of Patients
as Partners in Care.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166444.].
PMID- 28426756
TI - Excessive dietary intake of vitamin A reduces skull bone thickness in mice.
AB - Calvarial thinning and skull bone defects have been reported in infants with
hypervitaminosis A. These findings have also been described in humans, mice and
zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades
retinoic acid (RA), the active metabolite of vitamin A, indicating that these
effects are indeed caused by too high levels of vitamin A and that evolutionary
conserved mechanisms are involved. To explore these mechanisms, we have fed young
mice excessive doses of vitamin A for one week and then analyzed the skull bones
using micro computed tomography, histomorphometry, histology and
immunohistochemistry. In addition, we have examined the effect of RA on gene
expression in osteoblasts in vitro. Compared to a standard diet, a high dietary
intake of vitamin A resulted in a rapid and significant reduction in calvarial
bone density and suture diastasis. The bone formation rate was almost halved.
There was also increased staining of tartrate resistant acid phosphatase in
osteocytes and an increased perilacunar matrix area, indicating osteocytic
osteolysis. Consistent with this, RA induced genes associated with bone
degradation in osteoblasts in vitro. Moreover, and in contrast to other known
bone resorption stimulators, vitamin A induced osteoclastic bone resorption on
the endocranial surfaces.
PMID- 28426758
TI - Traces of business cycles in credit-rating migrations.
AB - Using migration data of a rating agency, this paper attempts to quantify the
impact of macroeconomic conditions on credit-rating migrations. The migrations
are modeled as a coupled Markov chain, where the macroeconomic factors are
represented by unobserved tendency variables. In the simplest case, these binary
random variables are static and credit-class-specific. A generalization treats
tendency variables evolving as a time-homogeneous Markov chain. A more detailed
analysis assumes a tendency variable for every combination of a credit class and
an industry. The models are tested on a Standard and Poor's (S&P's) dataset.
Parameters are estimated by the maximum likelihood method. According to the
estimates, the investment-grade financial institutions evolve independently of
the rest of the economy represented by the data. This might be an evidence of
implicit too-big-to-fail bail-out guarantee policies of the regulatory
authorities.
PMID- 28426759
TI - Health-related quality of life in South African patients with pulmonary
tuberculosis.
AB - BACKGROUND: The evaluation of patient-reported health-related quality of life
(HRQOL) in pulmonary tuberculosis (TB) contributes to a comprehensive
understanding of the burden associated with this disease. The aim of this study
was to assess the overall impact of TB on the health status and on single health
domains identified in the WHO definition of health, including physical, mental
and social health aspects. METHODS: Four instruments for HRQOL evaluation were
applied in a longitudinal multicentre study during six-month standard TB
treatment in South Africa. These included the generic SF-12 and EQ-5D-5L, the
disease-specific St. George's Respiratory Questionnaire (SGRQ) and the condition
specific Hospital Anxiety and Depression Scale (HADS). Statistical analysis
included significance testing, univariable and multivariable analysis, and
repeated measures ANOVA. Change over time in the physical component score (PCS)
of SF-12 was defined as primary endpoint. A target sample size of 96 patients was
estimated. RESULTS: HRQOL of the study participants was impaired in all physical,
mental and psycho-social health domains at treatment start. HRQOL improved
significantly and in a clinically meaningful manner during the course of standard
TB treatment, over the period of the study. The greatest improvement (95%) was
observed in mental health. Younger patients with higher education and who were
employed had a better HRQOL. DISCUSSION: This study demonstrates the need for an
integrative understanding of TB with HRQOL as core element to inform gaps in
current TB management. Improvements in the management of TB following an
integrative patient-centred approach will contribute towards meeting the United
Nations Sustainable Development Goal 3 (SDG3) target and will support the End TB
strategy of the WHO.
PMID- 28426761
TI - Correction: DHA Supplemented in Peptamen Diet Offers No Advantage in Pathways to
Amyloidosis: Is It Time to Evaluate Composite Lipid Diet?
AB - [This corrects the article DOI: 10.1371/journal.pone.0024094.].
PMID- 28426760
TI - Regulation of proteinaceous effector expression in phytopathogenic fungi.
AB - Effectors are molecules used by microbial pathogens to facilitate infection via
effector-triggered susceptibility or tissue necrosis in their host. Much research
has been focussed on the identification and elucidating the function of fungal
effectors during plant pathogenesis. By comparison, knowledge of how
phytopathogenic fungi regulate the expression of effector genes has been lagging.
Several recent studies have illustrated the role of various transcription
factors, chromosome-based control, effector epistasis, and mobilisation of
endosomes within the fungal hyphae in regulating effector expression and
virulence on the host plant. Improved knowledge of effector regulation is likely
to assist in improving novel crop protection strategies.
PMID- 28426762
TI - Human microRNA-299-3p decreases invasive behavior of cancer cells by
downregulation of Oct4 expression and causes apoptosis.
AB - PURPOSE: Oct4 was reported to be one of the most important pluripotency
transcription factors in the biology of stem cells including cancer stem cells,
and progressed malignant cells. Here we report the investigation of gene
expression control of Oct4 by selected human microRNAs and the physiological
effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS: High
throughput luciferase activity assay revealed the microRNA-299-3p to be the most
effective in reducing gene expression of Oct4, which was confirmed by Western
blot analysis and Oct4 promoter activity in a target luciferase assay.
Furthermore, it could be demonstrated that downregulation of Oct4 by microRNAs
299-3p in breast cancer and fibrosarcoma cells lead to a decreased invasiveness
in a microfluidic chip assay. Additionally, microRNA-299-3p causes apoptosis in
cancer cells. Comparison with Oct4 specific siRNA transfection confirmed that
this effect is primary due to the blockade of Oct4 expression. CONCLUSION: The
results suggest that microRNA-299-3p is an interesting target for potential
clinical use. It may be able to decrease invasive behaviour of carcinoma cells;
or even kill these cells by causing apoptosis.
PMID- 28426763
TI - Individual-based modelling of population growth and diffusion in discrete time.
AB - Individual-based models (IBMs) of human populations capture spatio-temporal
dynamics using rules that govern the birth, behavior, and death of individuals.
We explore a stochastic IBM of logistic growth-diffusion with constant time steps
and independent, simultaneous actions of birth, death, and movement that
approaches the Fisher-Kolmogorov model in the continuum limit. This model is well
suited to parallelization on high-performance computers. We explore its emergent
properties with analytical approximations and numerical simulations in parameter
ranges relevant to human population dynamics and ecology, and reproduce
continuous-time results in the limit of small transition probabilities. Our model
prediction indicates that the population density and dispersal speed are affected
by fluctuations in the number of individuals. The discrete-time model displays
novel properties owing to the binomial character of the fluctuations: in certain
regimes of the growth model, a decrease in time step size drives the system away
from the continuum limit. These effects are especially important at local
population sizes of <50 individuals, which largely correspond to group sizes of
hunter-gatherers. As an application scenario, we model the late Pleistocene
dispersal of Homo sapiens into the Americas, and discuss the agreement of model
based estimates of first-arrival dates with archaeological dates in dependence of
IBM model parameter settings.
PMID- 28426764
TI - Structural characterization of core-bradavidin in complex with biotin.
AB - Bradavidin is a tetrameric biotin-binding protein similar to chicken avidin and
bacterial streptavidin, and was originally cloned from the nitrogen-fixing
bacteria Bradyrhizobium diazoefficiens. We have previously reported the crystal
structure of the full-length, wild-type (wt) bradavidin with 138 amino acids,
where the C-terminal residues Gly129-Lys138 ("Brad-tag") act as an intrinsic
ligand (i.e. Gly129-Lys138 bind into the biotin-binding site of an adjacent
subunit within the same tetramer) and has potential as an affinity tag for
biotechnological purposes. Here, the X-ray structure of core-bradavidin lacking
the C-terminal residues Gly114-Lys138, and hence missing the Brad-tag, was
crystallized in complex with biotin at 1.60 A resolution [PDB:4BBO]. We also
report a homology model of rhodavidin, an avidin-like protein from
Rhodopseudomonas palustris, and of an avidin-like protein from Bradyrhizobium sp.
Ai1a-2, both of which have the Brad-tag sequence at their C-terminus. Moreover,
core-bradavidin V1, an engineered variant of the original core-bradavidin, was
also expressed at high levels in E. coli, as well as a double mutant (Cys39Ala
and Cys69Ala) of core-bradavidin (CC mutant). Our data help us to further
engineer the core-bradavidin-Brad-tag pair for biotechnological assays and
chemical biology applications, and provide deeper insight into the biotin-binding
mode of bradavidin.
PMID- 28426765
TI - Allatotropin: A pleiotropic neuropeptide that elicits mosquito immune responses.
AB - Allatotropins (AT) are neuropeptides with pleotropic functions on a variety of
insect tissues. They affect processes such as juvenile hormone biosynthesis,
cardiac rhythm, oviduct and hindgut contractions, nutrient absorption and
circadian cycle. The present work provides experimental evidence that AT elicits
immune responses in two important mosquito disease vectors, Anopheles albimanus
and Aedes aegypti. Hemocytes and an immune-competent mosquito cell line responded
to AT by showing strong morphological changes and increasing bacterial phagocytic
activity. Phenoloxidase activity in hemolymph was also increased in Ae. aegypti
mosquitoes treated with AT but not in An. albimanus, suggesting differences in
the AT-dependent immune activation in the two species. In addition, two important
insect immune markers, nitric oxide levels and expression of antimicrobial
peptide genes, were increased in An. albimanus guts after AT treatment. AT
conjugated to quantum dot nanocrystals (QDots) specifically labeled hemocytes in
vivo in both mosquito species, implying molecular interactions between AT and
hemocytes. The results of our studies suggest a new role for AT in the modulation
of the immune response in mosquitoes.
PMID- 28426766
TI - Activated entomopathogenic nematode infective juveniles release lethal venom
proteins.
AB - Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis
with entomopathogenic bacteria and their ability to kill insect hosts quickly
after infection. It is widely believed that EPNs rely on their bacterial partners
for killing hosts. Here we disproved this theory by demonstrating that the in
vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well
studied EPN species) release venom proteins that are lethal to several insects
including Drosophila melanogaster. We confirmed that the in vitro activation is a
good approximation of the in vivo process by comparing the transcriptomes of
individual in vitro and in vivo activated IJs. We further analyzed the
transcriptomes of non-activated and activated IJs and revealed a dramatic shift
in gene expression during IJ activation. We also analyzed the venom proteome
using mass spectrometry. Among the 472 venom proteins, proteases and protease
inhibitors are especially abundant, and toxin-related proteins such as Shk domain
containing proteins and fatty acid- and retinol-binding proteins are also
detected, which are potential candidates for suppressing the host immune system.
Many of the venom proteins have conserved orthologs in vertebrate-parasitic
nematodes and are differentially expressed during IJ activation, suggesting
conserved functions in nematode parasitism. In summary, our findings strongly
support a new model that S. carpocapsae and likely other Steinernema EPNs have a
more active role in contributing to the pathogenicity of the nematode-bacterium
complex than simply relying on their symbiotic bacteria. Furthermore, we propose
that EPNs are a good model system for investigating vertebrate- and human
parasitic nematodes, especially regarding the function of excretory/secretory
products.
PMID- 28426767
TI - Benign metastasizing leiomyoma: A review of current literature in respect to the
time and type of previous gynecological surgery.
AB - INTRODUCTION: Benign metastasizing leiomyoma (BML) is a rare disorder that
affects women with a history of uterine leiomyoma, which is found to metastasise
within extrauterine sites. The aetiology of BML remains unexplained. Because BML
is rare, and most publications contain descriptions of single cases, no
statistically determined time relations were found between the primary and
secondary surgeries, which may have aetiological implications. OBJECTIVES: To
determine age before BML surgery, age during diagnosis of BML, type of prior
surgery, and location of metastasis based on the literature. METHODS: A
systematic review of four databases (Medline/PubMed, Embase, Web of Science, and
Cochrane) covering articles published from 1 January 1965 to 10 April 2016. The
inclusion criteria were full-text articles in English and articles containing
case reports. Articles in languages other than English (39), articles containing
incomplete data (14), i.e. no information regarding the time of surgery and/or
the site of metastasis, articles bereft of case studies (25), and articles with
access only to summaries, without access to the complete text (10) were excluded.
Of 321 titles identified, only 126 articles met the aforementioned criteria.
RESULTS AND CONCLUSIONS: The mean age during primary surgery and BML diagnosis
was 38.5 years and 47.3 years, respectively. The most common surgery was total
hysterectomy. The most frequent site of metastasis was the lungs; other organs
were affected less frequently.The site of metastases and their number were not
related to the longer time span between the patient's initial surgery and
occurrence of metastasis. The analysed data, such as the age during primary
surgery, age during BML diagnosis, site and type of metastasis, do not provide us
a clear answer. Thus, BML pathogenesis is most probably complex in nature and
requires further multidirectional research.
PMID- 28426768
TI - Abundance of the iron containing biomolecule, heme b, during the progression of a
spring phytoplankton bloom in a mesocosm experiment.
AB - Concentrations of heme b were determined in a mesocosm experiment situated in
Gullmar Fjord off Sweden. The mesocosm experiment lasted for ca. one hundred days
and was characterised by the growth of a primary nutrient replete and a secondary
nutrient deplete phytoplankton bloom. Heme b varied between 40 +/- 10 pmol L-1 in
the prebloom period up to a maximum of 700 +/- 400 pmol L-1 just prior to the
time of the primary chlorophyll a maximum. Thereafter, heme b concentrations
decreased again to an average of 120 +/- 60 pmol L-1. When normalised to total
particulate carbon, heme b was most abundant during the initiation of the
nutrient replete spring bloom, when ratios reached 52 +/- 24 MUmol mol-1; ten
times higher than values observed both pre and post the primary bloom.
Concentrations of heme b correlated with those of chlorophyll a. Nevertheless,
differences were observed in the relative concentrations of the two parameters,
with heme b concentrations increasing relative to chlorophyll a during the growth
of the primary bloom, decreasing over the period of the secondary bloom and
increasing again through the latter period of the experiment. Heme b abundance
was therefore influenced by nutrient concentrations and also likely by changing
community composition. In half of the mesocosms, pCO2 was elevated and maintained
at ca.1000 MUatm, however we observed no significant differences between heme b
in plus or ambient pCO2 mesocosms, either in absolute terms, or relative to total
particulate carbon and chlorophyll a. The results obtained in this study
contribute to our understanding of the distribution of this significant component
of the biogenic iron pool, and provide an iron replete coastal water end member
that aids the interpretation of the distributions of heme b in more iron deplete
open ocean waters.
PMID- 28426769
TI - Examining drivers of the emissions embodied in trade.
AB - Emissions embodied in provincial trade (EEPT) have important effects on
provinces' responsibilities for carbon emission reductions. Based on a multi
regional input-output model, we calculated EEPT for China's 30 provinces in 2002,
2007 and 2010, and we attempted to determine the drivers of EEPT. The results
showed that, during this period, the ratio of EEPT to production-based emissions
increased over time, reaching 40.24% in 2010. In consideration of its important
role in carbon emissions, we analyzed the factors attributable to EEPT through
structure decomposition analysis. The decomposition results showed that final
demand and carbon emission intensity were two major factors in EEPT, while the
final demand in other provinces and the carbon emission intensity in the local
province were major factors for Emissions embodied in provincial exports and the
final demand in the local province and the carbon emission intensity in other
provinces were major factors for Emissions embodied in provincial imports.
Regarding the differences among the EEPT of different provinces, changes in the
structure of trade were the primary reason.
PMID- 28426770
TI - Correction: Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.
AB - [This corrects the article DOI: 10.1371/journal.pone.0159083.].
PMID- 28426771
TI - Correction: A systematic review of rodent pest research in Afro-Malagasy small
holder farming systems: Are we asking the right questions?
AB - [This corrects the article DOI: 10.1371/journal.pone.0174554.].
PMID- 28426772
TI - Correction: Chitosan-propolis nanoparticle formulation demonstrates anti
bacterial activity against Enterococcus faecalis biofilms.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174888.].
PMID- 28426773
TI - Correction: CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
AB - [This corrects the article DOI: 10.1371/journal.pone.0149099.].
PMID- 28426774
TI - The role of air pollution in myocardial remodeling.
AB - BACKGROUND: Excessive air pollution in urban environments can impact morbidity
and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in
structural, geometric, and functional remodeling in hearts, using an experimental
model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were
divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP),
myocardial infarcted group (MI), infarcted group immediately exposed to pollution
(IGP-I), and infarcted group previously exposed to pollution and kept exposed
after infarction (IGP-II). Greater deposition of interstitial collagen occurred
in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in
controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the
right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP
II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and
IGP-II). At the end of the study, CG had a higher mean shortening fraction than
the other groups had (p<=0.03). Left ventricular systolic diameter was lower in
CG than in infarcted groups (p<=0.003). The infarcted groups had greater
expression of TGF-beta (p<=0.04). PM2.5 increased the expression of TGF-beta in
the IGP-II compared with the MI group (p = 0.004). The TNF-alpha gene was
overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-gamma
gene expression was greater in IGP-II (p<=0.01). Oxidative stress analysis showed
a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I
(p = 0.008) compared with that in CG. CONCLUSIONS: PM2.5 stimulates the
deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted
hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP
II group. It also modulates oxidative stress in healthy hearts but not in
infarcted hearts.
PMID- 28426775
TI - Dynamic behaviors of a modified SIR model in epidemic diseases using nonlinear
incidence and recovery rates.
AB - The transmission of infectious diseases has been studied by mathematical methods
since 1760s, among which SIR model shows its advantage in its epidemiological
description of spread mechanisms. Here we established a modified SIR model with
nonlinear incidence and recovery rates, to understand the influence by any
government intervention and hospitalization condition variation in the spread of
diseases. By analyzing the existence and stability of the equilibria, we found
that the basic reproduction number [Formula: see text] is not a threshold
parameter, and our model undergoes backward bifurcation when there is limited
number of hospital beds. When the saturated coefficient a is set to zero, it is
discovered that the model undergoes the Saddle-Node bifurcation, Hopf
bifurcation, and Bogdanov-Takens bifurcation of codimension 2. The bifurcation
diagram can further be drawn near the cusp type of the Bogdanov-Takens
bifurcation of codimension 3 by numerical simulation. We also found a critical
value of the hospital beds bc at [Formula: see text] and sufficiently small a,
which suggests that the disease can be eliminated at the hospitals where the
number of beds is larger than bc. The same dynamic behaviors exist even when a ?
0. Therefore, it can be concluded that a sufficient number of the beds is
critical to control the epidemic.
PMID- 28426776
TI - Correction: Discovering SIFIs in Interbank Communities.
AB - [This corrects the article DOI: 10.1371/journal.pone.0167781.].
PMID- 28426777
TI - Rotavirus genome replication: Some assembly required.
PMID- 28426778
TI - ApaI polymorphism of vitamin D receptor affects health-related quality of life in
patients with primary sclerosing cholangitis.
AB - BACKGROUND: Polymorphisms of vitamin D receptor (VDR) contribute to the
pathogenesis of multiple autoimmune conditions. METHODS: We investigated the
incidence of VDR polymorphisms (rs1544410-BsmI; rs7975232-ApaI; rs731236-TaqI) in
a group of patients with primary sclerosing cholangitis (PSC, n = 275) and in
healthy controls (n = 376). Additionally, correlations of the VDR polymorphisms
with clinical and biochemical factors of the disease were analysed. RESULTS: The
genotype and allele distributions of these polymorphisms in PSC patients were
similar to those observed in controls. However, the ApaI polymorphism was
associated with an impaired health-related quality of life (HRQoL). The generic
SF-36 questionnaire showed that the Role-Physical (p = 0.01), Role-Emotional (p =
0.01), Physical Component Summary (p = 0.01) and Mental Component Summary (p =
0.003) scores were significantly affected. Similarly, the disease-specific
questionnaires, PBC-40 and PBC-27, demonstrated that carriers of the C allele
suffered from more severe Itch (p = 0.03 assessed by PBC-40 and PBC-27), more
Fatigue (p = 0.02 assessed by PBC-40 and PBC-27) and Impaired Cognitive Capacity
(p = 0.04 and p = 0.03). Correspondingly, individuals who were AA homozygotes
(non-carriers of the C allele of ApaI) had higher summary scores for the Physical
(p = 0.01) and Mental Components (p = 0.006) measured with SF-36. Moreover, they
experienced less itch (p = 0.03) and less Fatigue (p = 0.03) and had better
Cognitive Abilities (p = 0.04) as assessed by the PBC-40 and PBC-27
questionnaires. No associations between other VDR polymorphisms and clinical or
laboratory findings were made. CONCLUSION: In summary, this study is the first to
show that the ApaI polymorphisms in VDR may exert an effect on disease-related
symptoms and quality of life in patients with PSC.
PMID- 28426779
TI - Reference standards for lean mass measures using GE dual energy x-ray
absorptiometry in Caucasian adults.
AB - OBJECTIVE: To develop reference values by age and sex for LM measures using GE
Healthcare DXA systems. METHODS: A de-identified sample was obtained from Ball
State University's Clinical Exercise Physiology Laboratory and University of
Wisconsin-Milwaukee's Physical Activity & Health Research Laboratory. DXA scans
of 2,076 women and 1,251 men were completed using a GE Lunar Prodigy or iDXA.
Percentiles (%ile) were calculated for all variables of interest (LM, LMI, %LM,
and ALMI) and a factorial ANOVA was used to assess differences for each variable
between 10-year age groups and sex, as well as the interaction between age and
sex. RESULTS: Men had higher mean total LM, %LM, LMI, and ALMI than women
(p<0.01), across all age groups. All LM variables decreased significantly over
the 5 decades in men, however in women only total LM, %LM, and ALMI decreased
from the youngest to oldest age groups (p<0.01). CONCLUSION: These reference
values provide for a more accurate interpretation of GE-Healthcare DXA-derived LM
measurements offering clinicians and researchers with an initial resource to aid
in the early detection and assessment of LM deficits.
PMID- 28426780
TI - Response of spatial vegetation distribution in China to climate changes since the
Last Glacial Maximum (LGM).
AB - Analyzing how climate change affects vegetation distribution is one of the
central issues of global change ecology as this has important implications for
the carbon budget of terrestrial vegetation. Mapping vegetation distribution
under historical climate scenarios is essential for understanding the response of
vegetation distribution to future climatic changes. The reconstructions of
palaeovegetation based on pollen data provide a useful method to understand the
relationship between climate and vegetation distribution. However, this method is
limited in time and space. Here, using species distribution model (SDM)
approaches, we explored the climatic determinants of contemporary vegetation
distribution and reconstructed the distribution of Chinese vegetation during the
Last Glacial Maximum (LGM, 18,000 14C yr BP) and Middle-Holocene (MH, 6000 14C yr
BP). The dynamics of vegetation distribution since the LGM reconstructed by SDMs
were largely consistent with those based on pollen data, suggesting that the SDM
approach is a useful tool for studying historical vegetation dynamics and its
response to climate change across time and space. Comparison between the modeled
contemporary potential natural vegetation distribution and the observed
contemporary distribution suggests that temperate deciduous forests, subtropical
evergreen broadleaf forests, temperate deciduous shrublands and temperate steppe
have low range fillings and are strongly influenced by human activities. In
general, the Tibetan Plateau, North and Northeast China, and the areas near the
30 degrees N in Central and Southeast China appeared to have experienced the
highest turnover in vegetation due to climate change from the LGM to the present.
PMID- 28426781
TI - Tauroursodeoxycholic acid (TUDCA) attenuates pressure overload-induced cardiac
remodeling by reducing endoplasmic reticulum stress.
AB - Pressure overload in the heart induces pathological hypertrophy and is associated
with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the
endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive
effects. The aim of this study was to investigate whether reduction of ERS by a
known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate
pressure overload-induced cardiac remodeling in a mouse model of transverse
aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg
body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p
eIf2alpha), compared to the Vehicle (Veh)-TAC group. TUDCA administration, for 4
weeks after TAC significantly reduced cardiac hypertrophy as shown by the reduced
heart weight (HW) to BW ratio, and expression of hypertrophic marker genes (ANF,
BNP, and alpha-SKA). Masson's trichrome staining showed that myocardial fibrosis
and collagen deposition were also significantly reduced in the TUDCA-TAC group.
We also found that TUDCA significantly decreased expression of TGF-beta signaling
proteins and collagen isoforms. TUDCA administration also reduced cardiac
apoptosis and the related proteins in the TUDCA-TAC group. Microarray analysis
followed by gene ontology (GO) and pathway analysis demonstrated that
extracellular matrix genes responsible for hypertrophy and fibrosis, and
mitochondrial genes responsible for apoptosis and fatty acid metabolism were
significantly altered in the Veh-TAC group, but the alterations were normalized
in the TUDCA-TAC group, suggesting potential of TUDCA in treatment of heart
diseases related to pressure-overload.
PMID- 28426782
TI - Peste des petits ruminants (PPR): A neglected tropical disease in Maghreb region
of North Africa and its threat to Europe.
AB - BACKGROUND: Peste des petits ruminants (PPR) is a contagious disease listed by
the World Organisation for Animal health (OIE) as being a specific hazard. It
affects sheep, goats, and wild ungulates, and is prevalent throughout the
developing world particularly Asia, the Middle East, and Africa. PPR has been
targeted for eradication by 2030 by the Food and Agriculture Organization of the
United Nations (FAO) and the OIE, after the successful eradication of the related
disease, rinderpest in cattle. PPR was first reported in 1942 in the Ivory Coast
in Western Africa and has since extended its range in Asia, the Middle East, and
Africa posing an immediate threat of incursion into Europe, South East Asia and
South Africa. Although robust vaccines are available, the use of these vaccines
in a systematic and rational manner is not widespread, resulting in this
devastating disease becoming an important neglected tropical disease in the
developing world. METHODOLOGY: We isolated and characterized the PPR virus from
an outbreak in Cheraga, northern Algeria, during October 2015 by analyzing the
partial N-gene sequence in comparison with other viruses from the Maghreb region.
As well as sequencing the full length viral genome and performing real-time RT
PCR on clinical samples. Maximum-likelihood and Bayesian temporal and
phylogeographic analyses were performed to assess the persistence and spread of
PPRV circulation from Eastern Africa in the Maghreb region of North Africa.
CONCLUSIONS: Recent PPR outbreaks in Cheraga, in the northern part of Algiers
(October 2015) and North-West Morocco (June, 2015) highlight that PPRV has spread
to the northern border of North Africa and may pose a threat of introduction to
Europe. Phylogeographic analysis suggests that lineage IV PPRV has spread from
Eastern Africa, most likely from the Sudan 2000 outbreak, into Northern Africa
resulting in the 2008 Moroccan outbreak. Maximum-likelihood and Bayesian analysis
shows that these North African viruses cluster closely together suggesting the
existence of continual regional circulation. Considering the same virus is
circulating in Algeria, Morocco and Tunisia, implementation of a common Maghreb
PPR eradication strategy would be beneficial for the region.
PMID- 28426783
TI - Correction: Kinetics and Muscle Activity Patterns during Unweighting and
Reloading Transition Phases in Running.
AB - [This corrects the article DOI: 10.1371/journal.pone.0168545.].
PMID- 28426784
TI - Building on the success of soil-transmitted helminth control - The future of
deworming.
PMID- 28426785
TI - Genome-wide association studies identified multiple genetic loci for body size at
four growth stages in Chinese Holstein cattle.
AB - The growth and maturity of cattle body size affect not only feed efficiency, but
also productivity and longevity. Dissecting the genetic architecture of body size
is critical for cattle breeding to improve both efficiency and productivity. The
volume and weight of body size are indicated by several measurements. Among them,
Heart Girth (HG) and Hip Height (HH) are the most important traits. They are
widely used as predictors of body weight (BW). Few association studies have been
conducted for HG and HH in cattle focusing on single growth stage. In this study,
we extended the Genome-wide association studies to a full spectrum of four growth
stages (6-, 12-, 18-, and 24-months after birth) in Chinese Holstein heifers. The
whole genomic single nucleotide polymorphisms (SNPs) were obtained from the
Illumina BovineSNP50 v2 BeadChip genotyped on 3,325 individuals. Estimated
breeding values (EBVs) were derived for both HG and HH at the four different ages
and analyzed separately for GWAS by using the Fixed and random model Circuitous
Probability Unification (FarmCPU) method. In total, 27 SNPs were identified to be
significantly associated with HG and HH at different growth stages. We found 66
candidate genes located nearby the associated SNPs, including nine genes that
were known as highly related to development and skeletal and muscular growth. In
addition, biological function analysis was performed by Ingenuity Pathway
Analysis and an interaction network related to development was obtained, which
contained 16 genes out of the 66 candidates. The set of putative genes provided
valuable resources and can help elucidate the genomic architecture and mechanisms
underlying growth traits in dairy cattle.
PMID- 28426787
TI - Correction: Treatment with Riluzole Restores Normal Control of Soleus and
Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic
Nerve Crush at Birth.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170235.].
PMID- 28426786
TI - T140 blocks the SDF-1/CXCR4 signaling pathway and prevents cartilage degeneration
in an osteoarthritis disease model.
AB - Osteoarthritis (OA) is one of the most common diseases affecting older people;
however, there remains no effective targeted drug to combat OA. The aims of this
study were (1) to explore the effect of T140 in regulating degeneration of
articular cartilage in vivo by targeted blocking of the SDF-1/CXCR4 signaling
pathway, and (2) to provide experimental evidence for the development of a novel
OA-targeted pharmacotherapy. Thirty-six healthy Hartley guinea pigs were randomly
divided into three groups: a T140-treated group (n = 12), a phosphate buffer
saline control group (n = 12) and an untreated control group (n = 12). At 2, 4,
6, 8, 10 and 12 weeks of treatment, SDF-1 in serum was quantified by enzyme
linked immunosorbent assay. At 12 weeks of treatment, the cartilage from knee
tibial plateau in the knee joint was collected for H&E, Safranin-O staining and
Mankin grading; measurement for mRNA levels of matrix metalloproteinases (MMP-3,
MMP-9 and MMP-13), aggrecan (ACAN) and collagen II (Col II) using RT-PCR; and
measurement for Col II protein levels by western blot. Results showed that SDF-1
in serum increased in the T140 group and increased in the control groups. H&E and
Safranin-O staining revealed less cartilage loss in T140-treated animals compared
to controls. The mRNA levels of MMP-3, MMP-9 and MMP-13 in cartilage were much
lower in the T140 group than other groups, but mRNA levels of ACAN and Col II in
cartilage were higher in the T140-treated group. Col II protein levels in the
T140 group and control groups were different. T140 can downregulate the
expression of matrix-degrading enzyme and lessen the degeneration of cartilage by
blocking the SDF-1/CRCR4 signaling pathway in vivo. This mechanism may present a
pharmacological target for the treatment of OA.
PMID- 28426788
TI - Association between hemoglobin glycation index with insulin resistance and
carotid atherosclerosis in non-diabetic individuals.
AB - Hemoglobin glycation index (HGI), defined as the difference between the observed
HbA1c value and the value of HbA1c predicted from plasma glucose levels,
represents a measure of the degree of non-enzymatic glycation of hemoglobin and
it has been found to be positively associated with micro- and macro-vascular
complications in subjects with type 2 diabetes. To investigate the
pathophysiological abnormalities responsible for the increased cardiovascular
risk of patients with higher HGI, we evaluated the association of HGI with cardio
metabolic characteristics in nondiabetic offspring of type 2 diabetic
individuals. Insulin sensitivity, measured by a hyperinsulinemic-euglycemic
clamp, cardio-metabolic risk factors including lipid profile, uric acid and
inflammatory factors, and ultrasound measurement of carotid intima-media
thickness (IMT) were assessed in 387 nondiabetic individuals. Participants were
stratified in tertiles according to HGI (high, moderate and low). As compared
with subjects with low HGI, those with high HGI displayed an unfavorable cardio
metabolic risk profile having significantly higher values of BMI, waist
circumference, triglycerides, uric acid, fasting insulin, inflammatory markers,
such as high sensitivity C reactive protein, erythrocytes sedimentation rate,
complement C3, fibrinogen, and white blood cell count, and carotid IMT, and lower
HDL and insulin-stimulated glucose disposal. In a linear regression analysis
model including several atherosclerotic risk factors such as gender, age, BMI,
inflammatory factors, lipid profile, insulin-stimulated glucose disposal, fasting
insulin, uric acid, and blood pressure, HGI was the major predictor of IMT (beta
= 0.35; P = 0.001). In a logistic regression analysis adjusted for confounders,
individuals with high HGI showed a 2.7-fold increased risk of vascular
atherosclerosis (OR 2.72, 95%CI 1.01-7.37) as compared with subjects with low
HGI. The present findings support the notion that HGI may be a useful tool to
identify a subset of nondiabetic individuals conceivably harboring a higher risk
of cardiovascular disease.
PMID- 28426789
TI - Gre factors-mediated control of hilD transcription is essential for the invasion
of epithelial cells by Salmonella enterica serovar Typhimurium.
AB - The invasion of epithelial cells by Salmonella enterica serovar Typhimurium is a
very tightly regulated process. Signaling cascades triggered by different
environmental and physiological signals converge to control HilD, an AraC
regulator that coordinates the expression of several virulence factors. The
expression of hilD is modulated at several steps of the expression process. Here,
we report that the invasion of epithelial cells by S. Typhimurium strains lacking
the Gre factors, GreA and GreB, is impaired. By interacting with the RNA
polymerase secondary channel, the Gre factors prevent backtracking of paused
complexes to avoid arrest during transcriptional elongation. Our results indicate
that the Gre factors are required for the expression of the bacterial factors
needed for epithelial cell invasion by modulating expression of HilD. This
regulation does not occur at transcription initiation and depends on the capacity
of the Gre factors to prevent backtracking of the RNA polymerase. Remarkably,
genetic analyses indicate that the 3'-untranslated region (UTR) of hilD is
required for Gre-mediated regulation of hilD expression. Our data provide new
insight into the complex regulation of S. Typhimurium virulence and highlight the
role of the hilD 3'-UTR as a regulatory motif.
PMID- 28426791
TI - Correction: CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target
Prediction Tool.
AB - [This corrects the article DOI: 10.1371/journal.pone.0124633.].
PMID- 28426790
TI - Lethality of mice bearing a knockout of the Ngly1-gene is partially rescued by
the additional deletion of the Engase gene.
AB - The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating
enzyme that is highly conserved among eukaryotes. It was recently reported that
subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms
(NGLY1-deficiency). While the enzyme obviously has a critical role in mammals,
its precise function remains unclear. In this study, we analyzed Ngly1-deficient
mice and found that they are embryonic lethal in C57BL/6 background.
Surprisingly, the additional deletion of the gene encoding endo-beta-N
acetylglucosaminidase (Engase), which is another de-N-glycosylating enzyme but
leaves a single GlcNAc at glycosylated Asn residues, resulted in the partial
rescue of the lethality of the Ngly1-deficient mice. Additionally, we also found
that a change in the genetic background of C57BL/6 mice, produced by crossing the
mice with an outbred mouse strain (ICR) could partially rescue the embryonic
lethality of Ngly1-deficient mice. Viable Ngly1-deficient mice in a C57BL/6 and
ICR mixed background, however, showed a very severe phenotype reminiscent of the
symptoms of NGLY1-deficiency subjects. Again, many of those defects were strongly
suppressed by the additional deletion of Engase in the C57BL/6 and ICR mixed
background. The defects observed in Ngly1/Engase-deficient mice (C57BL/6
background) and Ngly1-deficient mice (C57BL/6 and ICR mixed background) closely
resembled some of the symptoms of patients with an NGLY1-deficiency. These
observations strongly suggest that the Ngly1- or Ngly1/Engase-deficient mice
could serve as a valuable animal model for studies related to the pathogenesis of
the NGLY1-deficiency, and that cytoplasmic ENGase represents one of the potential
therapeutic targets for this genetic disorder.
PMID- 28426792
TI - No evidence for the radiation time lag model after whole genome duplications in
Teleostei.
AB - The short and long term effects of polyploidization on the evolutionary fate of
lineages is still unclear despite much interest. First recognized in land plants,
it has become clear that polyploidization is widespread in eukaryotes, notably at
the origin of vertebrates and teleost fishes. Many hypotheses have been proposed
to link the species richness of lineages and whole genome duplications. For
instance, the radiation time lag model suggests that paleopolyploidy would favour
the apparition of new phenotypic traits, although the radiation of the lineage
would not occur before a later dispersion event. Some results indicate that this
model may be observed during land plant evolution. In this work, we test
predictions of the radiation time lag model using both fossil data and molecular
phylogenies in ancient and more recent teleost whole genome duplications. We fail
to find any evidence of delayed increase of the species number after any of these
events and conclude that paleopolyploidization still remains to be unambiguously
linked to taxonomic diversity in teleosts.
PMID- 28426793
TI - Prevalence of cardiovascular medication on secondary prevention after myocardial
infarction in China between 1995-2015: A systematic review and meta-analysis.
AB - BACKGROUND: Myocardial Infarction (MI) has become a major cause of morbidity and
mortality in China, but little is known about the prevalence of guideline
recommended cardiovascular medications after MI events over the last two decades.
This systematic review and meta-analysis aims to summarize cardiovascular
medication use between 1995-2015 and to assess factors in associated with the
trends in cardiovascular medications. METHOD: A systematic search was conducted
in four databases (Pubmed, Embase, CENTRAL, and CNKI) to obtain observational
studies published between 1995 and 2015, reporting on the use of cardiovascular
medications in China. Risk of bias of individual studies was appraised and
selected studies were pooled for estimated prevalence of cardiovascular
medication. Prevalence of cardiovascular medication use for 1995 and 2015 was
estimated by random effects meta-regression model. RESULTS: From 13,940
identified publications, 35 studies, comprising 28,000 patients, were included.
The pooled prevalence for aspirin, beta-blockers, statins, ACE-Inhibitors, ACE
Inhibitor/ARBs and nitrates was 92% [95% confidence interval (CI): 0.89-0.95],
63% (95% CI: 0.57-0.69), 72% (95% CI: 0.60-0.82), 49% (95% CI: 0.41-0.57), 59%
(95% CI: 0.48-0.69) and 79% (95% CI: 0.74-0.91), respectively. A significant
increase in beta-blocker and statin use and a decrease of nitrate use was
observed over time. The estimated prevalence of beta-blockers, statins, and
nitrates was 78%, 91.1%, and 59.3% in 2015, compared to 32%, 17% and 96% in 1995,
respectively. CONCLUSION: Cardiovascular medication use after MI is far from
optimal in Chinese patients, even though the prevalence of use increased over the
period 1995-2015. With a rapidly increasing number of MI patients in China, a
comprehensive strategy on secondary prevention is warranted. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO (CRD42015025246).
PMID- 28426794
TI - Impact of Wolbachia on oxidative stress sensitivity in the parasitic wasp Asobara
japonica.
AB - The oxidative homeostasis is the balance between reactive oxygen species and
antioxidant molecules. In addition to be considered as a key factor underlying
life-history traits evolution, the oxidative homeostasis has been shown to be
involved in many host-symbiont associations. Previous studies suggest an
interaction between the bacterial endosymbiont Wolbachia and the oxidative
homeostasis of some insect hosts. This interaction is likely to exert a strong
influence on the host evolution, as it has been proposed in the wasp Asobara
tabida, whose dependence upon Wolbachia is due to the evolutionary loss of its
ability to regulate the oxidative homeostasis in the absence of the symbiont.
Although such cases of complete dependence are rare, cases of insects having lost
only a part of their autonomy over the control of the oxidative homeostasis might
be more common. If so, one can expect that insects having coevolved with
Wolbachia will be more sensitive to oxidative stress when cured of their
symbionts. We tested this hypothesis by studying the effects of an experimentally
induced oxidative stress on various life-history traits of Asobara japonica, a
species closely related to A. tabida. For most of the life-history traits
studied, the sensitivity of the wasps to oxidative stress did not correlate with
their infection status. The only exception was the parasitic success. However,
contrarily to our expectation, the sensitivity to oxidative stress was increased,
rather than decreased, when Wolbachia was present. This result suggests that
Wolbachia does not participate to mitigate oxidative stress in A. japonica, and
that on the contrary its presence might still be costly in stressful
environments.
PMID- 28426795
TI - Properties of healthcare teaming networks as a function of network construction
algorithms.
AB - Network models of healthcare systems can be used to examine how providers
collaborate, communicate, refer patients to each other, and to map how patients
traverse the network of providers. Most healthcare service network models have
been constructed from patient claims data, using billing claims to link a patient
with a specific provider in time. The data sets can be quite large (106-108
individual claims per year), making standard methods for network construction
computationally challenging and thus requiring the use of alternate construction
algorithms. While these alternate methods have seen increasing use in generating
healthcare networks, there is little to no literature comparing the differences
in the structural properties of the generated networks, which as we demonstrate,
can be dramatically different. To address this issue, we compared the properties
of healthcare networks constructed using different algorithms from 2013 Medicare
Part B outpatient claims data. Three different algorithms were compared: binning,
sliding frame, and trace-route. Unipartite networks linking either providers or
healthcare organizations by shared patients were built using each method. We find
that each algorithm produced networks with substantially different topological
properties, as reflected by numbers of edges, network density, assortativity,
clustering coefficients and other structural measures. Provider networks adhered
to a power law, while organization networks were best fit by a power law with
exponential cutoff. Censoring networks to exclude edges with less than 11 shared
patients, a common de-identification practice for healthcare network data,
markedly reduced edge numbers and network density, and greatly altered measures
of vertex prominence such as the betweenness centrality. Data analysis identified
patterns in the distance patients travel between network providers, and a
striking set of teaming relationships between providers in the Northeast United
States and Florida, likely due to seasonal residence patterns of Medicare
beneficiaries. We conclude that the choice of network construction algorithm is
critical for healthcare network analysis, and discuss the implications of our
findings for selecting the algorithm best suited to the type of analysis to be
performed.
PMID- 28426796
TI - Correction: Side Effects in Time Discounting Procedures: Fixed Alternatives
Become the Reference Point.
AB - [This corrects the article DOI: 10.1371/journal.pone.0165245.].
PMID- 28426797
TI - Is bilingualism losing its advantage? A bibliometric approach.
AB - This study uses several bibliometric indices to explore the temporal course of
publication trends regarding the bilingual advantage in executive control over a
ten-year window. These indices include the number of published papers, numbers of
citations, and the journal impact factor. According to the information available
in their abstracts, studies were classified into one of four categories:
supporting, ambiguous towards, not mentioning, or challenging the bilingual
advantage. Results show that the number of papers challenging the bilingual
advantage increased notably in 2014 and 2015. Both the average impact factor and
the accumulated citations as of June 2016 were equivalent between categories.
However, of the studies published in 2014, those that challenge the bilingual
advantage accumulated more citations in June 2016 than those supporting it. Our
findings offer evidence-based bibliometric information about the current state of
the literature and suggest a change in publication trends regarding the
literature on the bilingual advantage.
PMID- 28426798
TI - Glucotoxicity induces abnormal glucagon secretion through impaired insulin
signaling in InR1G cells.
AB - The significance of glucagon in the pathophysiology of diabetes mellitus is
widely recognized, but the mechanisms underlying dysregulated glucagon secretion
are still unclear. Here, we explored the molecular mechanisms of glucagon
dysregulation, using an in vitro model. Hamster-derived glucagon-secreting InR1G
cells were exposed to high glucose (25 mM) levels for 12 h before analyzing
glucagon secretion and the activity of components involved in insulin signaling.
High-glucose treatment induced increased glucagon secretion in InR1G cells, which
represents a hallmark of diabetes mellitus. This treatment reduced the
phosphorylation of Akt, indicating the deterioration of insulin signaling.
Simultaneously, oxidative stress and JNK activity were shown to be increased. The
inhibition of JNK signaling resulted in the amelioration of high-glucose level
induced glucagon secretion. Abnormally elevated glucagon secretion in diabetes
can be reproduced by high-glucose treatment of InR1G cells, and the involvement
of high glucose-oxidative stress-JNK-insulin signaling pathway axis has been
demonstrated. These data elucidate, at least partly, the previously unclear
mechanism of abnormal glucagon secretion, providing insights into a potential
novel approach to diabetes treatment, targeting glucagon.
PMID- 28426799
TI - Cell cycle profiling by image and flow cytometry: The optimised protocol for the
detection of replicational activity using 5-Bromo-2'-deoxyuridine, low
concentration of hydrochloric acid and exonuclease III.
AB - The approach for the detection of replicational activity in cells using 5-bromo
2'-deoxyuridine, a low concentration of hydrochloric acid and exonuclease III is
presented in the study. The described method was optimised with the aim to
provide a fast and robust tool for the detection of DNA synthesis with minimal
impact on the cellular structures using image and flow cytometry. The approach is
based on the introduction of breaks into the DNA by the low concentration of
hydrochloric acid followed by the subsequent enzymatic extension of these breaks
using exonuclease III. Our data showed that the method has only a minimal effect
on the tested protein localisations and is applicable both for formaldehyde- and
ethanol-fixed cells. The approach partially also preserves the fluorescence of
the fluorescent proteins in the HeLa cells expressing Fluorescent Ubiquitin Cell
Cycle Indicator. In the case of the short labelling pulses that disabled the use
of 5-ethynyl-2'-deoxyuridine because of the low specific signal, the described
method provided a bright signal enabling reliable recognition of replicating
cells. The optimized protocol was also successfully tested for the detection of
trifluridine, the nucleoside used as an antiviral drug and in combination with
tipiracil also for the treatment of some types of cancer.
PMID- 28426800
TI - Neutrophil-lymphocyte ratio predicts short term mortality in patients with
hepatitis B virus-related acute-on-chronic liver failure treated with an
artificial liver support system.
AB - AIM: Hepatitis B virus-related acute-on-chronic liver failure has high short-term
mortality. Artificial liver support systems (ALSS) may improve outcome and avoid
liver transplantation, but predicting short-term prognosis in such patients is
difficult. This study aimed to determine whether the neutrophil-lymphocyte ratio
(NLR), an inflammation marker, predicted mortality in patients treated with ALSS.
METHODS: A total of 560 patients with hepatitis B virus-related acute-on-chronic
liver failure were enrolled, 338 were treated with ALSS and the others treated
with standard of care(SOC). Clinical variables and the NLR were evaluated for
prognostic value. RESULTS: Thirty-day mortality was 28.4% in ALSS and 55.4% in
SOC patients. The NLR was lower in survivors than in ALSS or SOC patients who
died. Univariate and multivariate analysis found that NLR and the chronic liver
failure sequential organ failure assessment scores(CLIF-SOFA) were independently
associated with 30-day mortality. Among patients with NLRs <= 3, 3-6, and >6, 30
day mortality was 7.7%,23.1%, and 69.2% in ALSS and 25.5%, 50.0%, and 75.0% in
SOC patients. Among patients with NLRs <= 3 or 3-6, mortality was lower in ALSS
than in SOC patients (P < 0.01). Mortality rates of ALSS and SOC patients with
NLRs > 6 did not different (P >0.05). The area under curve of NLR and CLIF-SOFA
was 0.82 and 0.88 in ALSS group, 0.78 and 0.86 in SOC group. The results suggest
that liver function in most patients with NLRs <= 3 recovered with ALSS
treatment, and patients with NLRs > 6 needed emergency liver transplantation.
CONCLUSION: NLR was an independent predictor of mortality in ALSS patients and
may assist physicians in determining treatment options.
PMID- 28426801
TI - The change of serum tumor necrosis factor alpha in patients with type 1 diabetes
mellitus: A systematic review and meta-analysis.
AB - OBJECTIVE: The aim of this study was used meta-analysis to investigate changes of
serum tumor necrosis factor-alpha (TNF-alpha) in patients with type 1 diabetes
mellitus (T1DM). METHODS: Relevant literatures were identified from PubMed,
Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from
January 1, 1999 to September 30, 2016). Eligible reports were included for pooled
analysis of serum TNF-alpha level and subgroup analysis was performed in relation
with age, disease duration and ethnicity. RESULTS: A total of 23 articles (1631
T1DM cases, 1429 healthy controls) were included for this meta-analysis. Compared
with the controls, the patients had significantly increased serum TNF-alpha level
(P < 0.001). Similar results were also found among all subgroup analysis of
different age, disease duration and ethnicity (with the exception of Asian) (all
P < 0.05). Regression analysis indicated that age (P = 0.680), disease duration
(P = 0.957), and ethnicity (P = 0.526) of patients were not significant impact
factors for the high heterogeneity. The results were stable according to the
sensitivity analysis and no publication bias existed in this meta-analysis.
CONCLUSIONS: Serum TNF-alpha level in T1DM patients has significantly elevated
among all age, disease duration and ethnicity groups.
PMID- 28426802
TI - Decoding the infant mind: Multivariate pattern analysis (MVPA) using fNIRS.
AB - The MRI environment restricts the types of populations and tasks that can be
studied by cognitive neuroscientists (e.g., young infants, face-to-face
communication). FNIRS is a neuroimaging modality that records the same
physiological signal as fMRI but without the constraints of MRI, and with better
spatial localization than EEG. However, research in the fNIRS community largely
lacks the analytic sophistication of analogous fMRI work, restricting the
application of this imaging technology. The current paper presents a method of
multivariate pattern analysis for fNIRS that allows the authors to decode the
infant mind (a key fNIRS population). Specifically, multivariate pattern analysis
(MVPA) employs a correlation-based decoding method where a group model is
constructed for all infants except one; both average patterns (i.e., infant
level) and single trial patterns (i.e., trial-level) of activation are decoded.
Between subjects decoding is a particularly difficult task, because each infant
has their own somewhat idiosyncratic patterns of neural activation. The fact that
our method succeeds at across-subject decoding demonstrates the presence of group
level multi-channel regularities across infants. The code for implementing these
analyses has been made readily available online to facilitate the quick adoption
of this method to advance the methodological tools available to the fNIRS
researcher.
PMID- 28426803
TI - Dendritic cell maturation, but not type I interferon exposure, restricts
infection by HTLV-1, and viral transmission to T-cells.
AB - Human T lymphotropic Virus type 1 (HTLV-1) is the etiological agent of Adult T
cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic
Paraparesis (HAM/TSP). Both CD4+ T-cells and dendritic cells (DCs) infected with
HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously
demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1
infection than autologous primary T-cells, suggesting that DC infection precedes
T-cell infection. However, during blood transmission, breast-feeding or sexual
transmission, HTLV-1 may encounter different DC subsets present in the blood, the
intestinal or genital mucosa respectively. These different contacts may impact
HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in
vitro monocyte-derived IL-4 DCs, TGF-beta DCs and IFN-alpha DCs that mimic DCs
contacting HTLV-1 in vivo, we show here that despite their increased ability to
capture HTLV-1 virions, IFN-alpha DCs restrict HTLV-1 productive infection.
Surprisingly, we then demonstrate that it is not due to the antiviral activity of
type-I interferon produced by IFN-alpha DCs, but that it is likely to be linked
to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-alpha DCs. Finally,
we demonstrate that, in contrast to IL-4 DCs, IFN-alpha DCs are impaired in their
capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans
infection and after their productive infection. In conclusion, the nature of the
DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route
through the vesicular pathway of these cells determine the efficiency of viral
transmission to T-cells, which may condition the fate of infection.
PMID- 28426804
TI - DNA damage induces expression of WWP1 to target DeltaNp63alpha to degradation.
AB - DeltaNp63alphaplays key roles in cell survival and proliferation. So its
expression is always tightly controlled in cells. We previously reported that DNA
damage down-regulates transcription of DeltaNp63alphain FaDu and HaCat cells,
which contributes to cell apoptosis. In the present study, we found that DNA
damage induces down-regulation of DeltaNp63alphavia facilitating its proteasomal
degradation in cell lines such as MDA-MB-231 and MCF10A. Further investigation
revealed that transcription of WWP1 is stimulated by DNA damage in these cells.
Knock-down of WWP1 abrogates DNA damage-induced down-regulation of
DeltaNp63alphaand partially rescues cell apoptosis. Interestingly, DNA damage may
stimulate WWP1 through different mechanisms in different cell types: it up
regulates transcription of WWP1 in a p53-dependent manner in MCF10A and HEK293
cells, while miR-452 may be involved in DNA damage-induced up-regulation of WWP1
in MDA-MB-231 cells. Our study demonstrates a novel pathway which regulates
DeltaNp63alphaupon cellular response to chemotherapeutic agents.
PMID- 28426805
TI - Evidence of horizontal gene transfer by transposase gene analyses in
Fervidobacterium species.
AB - Horizontal Gene Transfer (HGT) plays an important role in the physiology and
evolution of microorganisms above all thermophilic prokaryotes. Some members of
the Phylum Thermotogae (i.e., Thermotoga spp.) have been reported to present
genomes constituted by a mosaic of genes from a variety of origins. This study
presents a novel approach to search on the potential plasticity of
Fervidobacterium genomes using putative transposase-encoding genes as the target
of analysis. Transposases are key proteins involved in genomic DNA
rearrangements. A comprehensive comparative analysis, including phylogeny, non
metric multidimensional scaling analysis of tetranucleotide frequencies,
repetitive flanking sequences and divergence estimates, was performed on the
transposase genes detected in four Fervidobacterium genomes: F. nodosum, F.
pennivorans, F. islandicum and a new isolate (Fervidobacterium sp. FC2004).
Transposase sequences were classified in different groups by their degree of
similarity. The different methods used in this study pointed that over half of
the transposase genes represented putative HGT events with closest relative
sequences within the phylum Firmicutes, being Caldicellulosiruptor the genus
showing highest gene sequence proximity. These results confirmed a direct
evolutionary relationship through HGT between specific Fervidobacterium species
and thermophilic Firmicutes leading to potential gene sequence and functionality
sharing to thrive under similar environmental conditions. Transposase-encoding
genes represent suitable targets to approach the plasticity and potential
mosaicism of bacterial genomes.
PMID- 28426807
TI - Correction: Risk factors associated with sexually transmitted infections among
HIV infected men who have sex with men.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170635.].
PMID- 28426806
TI - The crystal structure of Erwinia amylovora AmyR, a member of the YbjN protein
family, shows similarity to type III secretion chaperones but suggests different
cellular functions.
AB - AmyR is a stress and virulence associated protein from the plant pathogenic
Enterobacteriaceae species Erwinia amylovora, and is a functionally conserved
ortholog of YbjN from Escherichia coli. The crystal structure of E. amylovora
AmyR reveals a class I type III secretion chaperone-like fold, despite the lack
of sequence similarity between these two classes of protein and lacking any
evidence of a secretion-associated role. The results indicate that AmyR, and YbjN
proteins in general, function through protein-protein interactions without any
enzymatic action. The YbjN proteins of Enterobacteriaceae show remarkably low
sequence similarity with other members of the YbjN protein family in Eubacteria,
yet a high level of structural conservation is observed. Across the YbjN protein
family sequence conservation is limited to residues stabilising the protein core
and dimerization interface, while interacting regions are only conserved between
closely related species. This study presents the first structure of a YbjN
protein from Enterobacteriaceae, the most highly divergent and well-studied
subgroup of YbjN proteins, and an in-depth sequence and structural analysis of
this important but poorly understood protein family.
PMID- 28426808
TI - A screen for protective drugs against delayed hypoxic injury.
AB - Despite longstanding efforts to develop cytoprotective drugs against
ischemia/reperfusion (IR) injuries, there remains no effective therapeutics to
treat hypoxic injury. The failure of traditional strategies at solving this
problem suggests the need for novel and unbiased approaches that can lead to
previously unsuspected targets and lead compounds. Towards this end, we report
here a unique small molecule screen in the nematode C. elegans for compounds that
improve recovery when applied after the hypoxic insult, using a C. elegans strain
engineered to have delayed cell non-autonomous death. In a screen of 2000
compounds, six were found to produce significant protection of C. elegans from
delayed death. Four of the compounds were tested in an ex vivo mouse heart
ischemia/reperfusion model and two, meclocycline and 3-amino-1,2,4-triazole,
significantly reduced infarction size. Our work demonstrates the feasibility of
this novel C. elegans screen to discover hypoxia protective drugs that are also
protective in a mammalian model of hypoxic injury.
PMID- 28426809
TI - Denaturation of proteins by surfactants studied by the Taylor dispersion
analysis.
AB - We showed that the Taylor Dispersion Analysis (TDA) is a fast and easy to use
method for the study of denaturation proteins. We applied TDA to study
denaturation of beta-lactoglobulin, transferrin, and human insulin by anionic
surfactant sodium dodecyl sulfate (SDS). A series of measurements at constant
protein concentration (for transferrin was 1.9 x 10-5 M, for beta- lactoglobulin
was 7.6 x 10-5 M, and for insulin was 1.2 x 10-4 M) and varying SDS
concentrations were carried out in the phosphate-buffered saline (PBS). The
structural changes were analyzed based on the diffusion coefficients of the
complexes formed at various surfactant concentrations. The concentration of
surfactant was varied in the range from 1.2 x 10-4 M to 8.7 x 10-2 M. We
determined the minimum concentration of the surfactant necessary to change the
native conformation of the proteins. The minimal concentration of SDS for beta
lactoglobulin and transferrin was 4.3 x 10-4 M and for insulin 2.3 x 10-4 M. To
evaluate the TDA as a novel method for studying denaturation of proteins we also
applied other methods i.e. electronic circular dichroism (ECD) and dynamic light
scattering (DLS) to study the same phenomenon. The results obtained using these
methods were in agreement with the results from TDA.
PMID- 28426810
TI - Correction: miRNAs in the vitreous humor of patients affected by idiopathic
epiretinal membrane and macular hole.
AB - [This corrects the article DOI: 10.1371/journal.pone.0174297.].
PMID- 28426811
TI - Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk
community-acquired pneumonia using a rapid point-of-care testing: A single-arm
clinical trial.
AB - OBJECTIVE: We aimed to assess the role of procalcitonin (PCT) to guide the
initial selection of the antibiotic regimen for low-risk community-acquired
pneumonia (CAP). METHODS: A single-arm clinical trial was conducted including
outpatients with CAP and Pneumonia Severity Index risk classes I-II.
Antimicrobial selection was based on the results of PCT measured with a rapid
point-of-care testing. According to serum PCT levels, patients were assigned to
two treatment strategies: oral azithromycin if PCT was <0.5 ng/ml, or
levofloxacin if levels were >=0.5 ng/ml. Primary outcome was clinical cure rate.
Short-term and long-term outcomes were assessed. Results were compared with those
of a historical standard-of-care control-group treated in our centre. RESULTS: Of
253 subjects included, 216 (85.4%) were assigned to azithromycin. Pneumococcal
infection was diagnosed in 26 (12%) and 21 (56.8%) patients allocated to
azithromycin and levofloxacin groups, respectively. No patients in the
azithromycin group developed bacteraemia. Atypical organisms were more common in
patients given azithromycin (18.5% vs 8.1%, respectively). The majority (93%) of
patients with atypical pneumonia had low PCT levels. Clinical cure rates were
95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in
the historical control group. No 30-day mortality or recurrences were observed,
and the 3-year rates of recurrence and mortality were very low in both groups.
Adverse events occurrence was also infrequent. CONCLUSION: A PCT-guided strategy
with a rapid point-of-care testing safely allowed selecting empirical narrow
spectrum antibiotics in outpatients with CAP. TRIAL REGISTRATION: The study is
registered with ClinicalTrials.gov, number NCT02600806.
PMID- 28426812
TI - Religion and the public ethics of stem-cell research: Attitudes in Europe, Canada
and the United States.
AB - We examine international public opinion towards stem-cell research during the
period when the issue was at its most contentious. We draw upon representative
sample surveys in Europe and North America, fielded in 2005 and find that the
majority of people in Europe, Canada and the United States supported stem-cell
research, providing it was tightly regulated, but that there were key differences
between the geographical regions in the relative importance of different types of
ethical position. In the U.S., moral acceptability was more influential as a
driver of support for stem-cell research; in Europe the perceived benefit to
society carried more weight; and in Canada the two were almost equally important.
We also find that public opinion on stem-cell research was more strongly
associated with religious convictions in the U.S. than in Canada and Europe,
although many strongly religious citizens in all regions approved of stem-cell
research. We conclude that if anything public opinion or 'public ethics' are
likely to play an increasingly important role in framing policy and regulatory
regimes for sensitive technologies in the future.
PMID- 28426813
TI - Correction: Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves
reduces colon cancer growth and induces caspase-dependent apoptosis in colon
cancer cells via the mitochondrial apoptotic pathway.
AB - [This corrects the article DOI: 10.1371/journal.pone.0170823.].
PMID- 28426814
TI - Progress and projections in the program to eliminate trachoma.
PMID- 28426815
TI - Using controlled attenuation parameter combined with ultrasound to survey non
alcoholic fatty liver disease in hemodialysis patients: A prospective cohort
study.
AB - BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a non-invasive
method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease
(NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the
leading cause of morbidity and mortality in hemodialysis patients. The aim of
this study was to investigate the prevalence of NAFLD in hemodialysis patients.
METHOD: We prospectively enrolled patients undergoing chronic hemodialysis, as
well as patients with normal renal function who served as controls. The control
group patients were referred by an endocrinologist to be tested for NAFLD; most
of these patients had diabetes, hypertension, or dyslipidemia. We excluded those
with excess alcohol intake, use of drugs known to induce HS, chronic viral
hepatitis, or CAP failure. CAP >= 238 dB/m was used as a cutoff suggesting HS. An
increased liver kidney contrast, as defined by ultrasound, was used to make the
diagnosis of HS. RESULTS: Three hundred and forty-three hemodialysis patients and
252 control group patients were enrolled. Among the hemodialysis patients, 192
(56.0%) had CAP- or ultrasound-identified HS compared with 91 (26.5%) who only
had ultrasound-identified HS (P<0.001). Among the control group patients, 212
(84.1%) had CAP- or ultrasound-identified HS compared with 180 (71.4%) who only
had ultrasound-identified HS (P<0.001). CONCLUSIONS: The prevalence of NAFLD in
the hemodialysis patients was 56%. The number of diagnoses of NAFLD made by using
CAP combined with ultrasound was more than 2 times the number made with
ultrasound alone in the hemodialysis patients. Therefore, we suggest the use of
CAP combined with ultrasound to screen for NAFLD in hemodialysis patients.
PMID- 28426816
TI - Ex vivo cultures combined with vivo-morpholino induced gene knockdown provide a
system to assess the role of WT1 and GATA4 during gonad differentiation.
AB - Gonad morphogenesis relies on the correct spatiotemporal expression of a number
of genes that together fulfill the differentiation of the bipotential gonad into
testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal
for proper gonadal development. Here we address the contributions of GATA4 and
WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo
technique for cultivating gonads in hanging droplets of media that were
supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in
combination at the same developmental stage. We show that WT1 is equally
important for both, the initial establishment and the maintenance of the sex
specific gene expression signature in testes and ovaries. We further identified
Foxl2 as a novel putative downstream target gene of WT1. Moreover, knockdown of
WT1 reduced mRNA levels of several molecular components of the hedgehog signaling
pathway in XY gonads, whereas Gata4 vivo-morpholino treatment increased
transcripts of Dhh and Ptch1 in embryonic testes. The data suggest that for its
proper function, WT1 relies on the correct expression of the GATA4 protein.
Furthermore, GATA4 down-regulates several ovarian promoting genes in testes, such
as Ctnnb1, Fst, and Bmp2, suggesting that this repression is required for
maintaining the male phenotype. In conclusion, this study provides novel insights
into the role of WT1 and GATA4 during the sex differentiation phase and
represents an approach that can be applied to assess other proteins with as yet
unknown functions during gonadal development.
PMID- 28426817
TI - Evaluation of machine learning algorithms and structural features for optimal MRI
based diagnostic prediction in psychosis.
AB - A relatively large number of studies have investigated the power of structural
magnetic resonance imaging (sMRI) data to discriminate patients with
schizophrenia from healthy controls. However, very few of them have also included
patients with bipolar disorder, allowing the clinically relevant discrimination
between both psychotic diagnostics. To assess the efficacy of sMRI data for
diagnostic prediction in psychosis we objectively evaluated the discriminative
power of a wide range of commonly used machine learning algorithms (ridge, lasso,
elastic net and L0 norm regularized logistic regressions, a support vector
classifier, regularized discriminant analysis, random forests and a Gaussian
process classifier) on main sMRI features including grey and white matter voxel
based morphometry (VBM), vertex-based cortical thickness and volume, region of
interest volumetric measures and wavelet-based morphometry (WBM) maps. All
possible combinations of algorithms and data features were considered in pairwise
classifications of matched samples of healthy controls (N = 127), patients with
schizophrenia (N = 128) and patients with bipolar disorder (N = 128). Results
show that the selection of feature type is important, with grey matter VBM
(without data reduction) delivering the best diagnostic prediction rates
(averaging over classifiers: schizophrenia vs. healthy 75%, bipolar disorder vs.
healthy 63% and schizophrenia vs. bipolar disorder 62%) whereas algorithms
usually yielded very similar results. Indeed, those grey matter VBM accuracy
rates were not even improved by combining all feature types in a single
prediction model. Further multi-class classifications considering the three
groups simultaneously made evident a lack of predictive power for the bipolar
group, probably due to its intermediate anatomical features, located between
those observed in healthy controls and those found in patients with
schizophrenia. Finally, we provide MRIPredict
(https://www.nitrc.org/projects/mripredict/), a free tool for SPM, FSL and R, to
easily carry out voxelwise predictions based on VBM images.
PMID- 28426818
TI - Alternative glacial-interglacial refugia demographic hypotheses tested on
Cephalocereus columna-trajani (Cactaceae) in the intertropical Mexican drylands.
AB - Historic demography changes of plant species adapted to New World arid
environments could be consistent with either the Glacial Refugium Hypothesis
(GRH), which posits that populations contracted to refuges during the cold-dry
glacial and expanded in warm-humid interglacial periods, or with the Interglacial
Refugium Hypothesis (IRH), which suggests that populations contracted during
interglacials and expanded in glacial times. These contrasting hypotheses are
developed in the present study for the giant columnar cactus Cephalocereus
columna-trajani in the intertropical Mexican drylands where the effects of Late
Quaternary climatic changes on phylogeography of cacti remain largely unknown. In
order to determine if the historic demography and phylogeographic structure of
the species are consistent with either hypothesis, sequences of the chloroplast
regions psbA-trnH and trnT-trnL from 110 individuals from 10 populations
comprising the full distribution range of this species were analysed. Standard
estimators of genetic diversity and structure were calculated. The historic
demography was analysed using a Bayesian approach and the palaeodistribution was
derived from ecological niche modelling to determine if, in the arid environments
of south-central Mexico, glacial-interglacial cycles drove the genetic divergence
and diversification of this species. Results reveal low but statistically
significant population differentiation (FST = 0.124, P < 0.001), although very
clear geographic clusters are not formed. Genetic diversity, haplotype network
and Approximate Bayesian Computation (ABC) demographic analyses suggest a
population expansion estimated to have taken place in the Last Interglacial
(123.04 kya, 95% CI 115.3-130.03). The species palaeodistribution is consistent
with the ABC analyses and indicates that the potential area of palaedistribution
and climatic suitability were larger during the Last Interglacial and Holocene
than in the Last Glacial Maximum. Overall, these results suggest that C. columna
trajani experienced an expansion following the warm conditions of interglacials,
in accordance with the GRH.
PMID- 28426820
TI - The influence of cell membrane and SNAP25 linker loop on the dynamics and
unzipping of SNARE complex.
AB - The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
complex is composed of three neuronal proteins VAMP2, Syntaxin and SNAP25, which
plays a core role during the process of membrane fusion. The zipping assembly of
the SNARE complex releases energies and drives the vesicle and cell membrane into
close proximity. In this study, we use all-atom molecular dynamics simulations to
probe the dynamics of SNARE and its unzipping process in the context of membrane
at the atomistic details. Our results indicated that the NTD of SNARE core domain
is relatively more stable than CTD, which is in agreement with previous
experiments. More importantly, possible interactions between the linker loop (LL)
region of SNAP25 and VAMP2 are observed, suggests that the LL region may
facilitate VAMP2 binding and SNARE initiation. The forced unzipping of SNARE in
the presence of membrane and LL of SNAP25 reveals the possible pathway for energy
generation of SNARE zipping, provides information to understand how force may
regulate the cooperativity between the membrane and the SNARE complex.
PMID- 28426819
TI - Virological success after 12 and 24 months of antiretroviral therapy in sub
Saharan Africa: Comparing results of trials, cohorts and cross-sectional studies
using a systematic review and meta-analysis.
AB - BACKGROUND: UNAIDS recently defined the 90-90-90 target as a way to end the HIV
epidemic. However, the proportion of virological success following antiretroviral
therapy (ART) may not be as high as the anticipated 90%, and may in fact be
highly heterogeneous. We aimed to describe the proportion of virological success
in sub-Saharan Africa and to identify factors associated with the proportion of
virological success. METHODS: We performed a systematic review and meta-analysis
focusing on the proportion of patients in sub-Saharan Africa who demonstrate
virological success at 12 and 24 months since ART initiation, as well as at 6 and
36 months, where possible. Programme factors associated with the proportion of
virological success were identified using meta-regression. Analyses were
conducted using both on-treatment (OT) and intention-to-treat (ITT) approaches.
RESULTS: Eighty-five articles were included in the meta-analysis, corresponding
to 125 independent study populations. Using an on-treatment approach, the
proportions (95% confidence interval (CI)) of virological success at 12 (n = 64)
and at 24 (n = 32) months since ART initiation were 87.7% (81.3-91.0) and 83.7%
(79.8-87.6), respectively. Univariate analysis indicated that the proportion of
virological success was not different by study design. Multivariate analysis at
24 months showed that the proportion of virological success was significantly
larger in studies conducted in public sector sites than in other sites (p =
0.045). Using an ITT approach, the proportions (95% CI) of virological success at
12 (n = 50) and at 24 (n = 20) months were 65.4% (61.8-69.1) and 56.8% (51.3
62.4), respectively. At 12 months, multivariate analysis showed that the
proportion of success was significantly lower in cohort studies than in trials
(63.0% vs. 71.1%; p = 0.017). At 24 months, univariate analysis demonstrated that
the proportion of success was also lower in cohorts. DISCUSSION: Regardless of
the time following ART initiation, and of the threshold, proportions of
virological success were highly variable. Evidence from this review suggests that
the new international target of 90% of patients controlled is not yet being
achieved, and that in order to improve the virological outcome, efforts should be
made to improve retention in care.
PMID- 28426821
TI - The importance of model systems: Why we study a virus on the brink of global
eradication.
PMID- 28426822
TI - Genomics of a revived breed: Case study of the Belgian campine cattle.
AB - Through centuries of both natural and artificial selection, a variety of local
cattle populations arose with highly specific phenotypes. However, the
intensification and expansion of scale in animal production systems led to the
predominance of a few highly productive cattle breeds. The loss of local
populations is often considered irreversible and with them specific qualities and
rare variants could be lost as well. Over these last years, the interest in these
local breeds has increased again leading to increasing efforts to conserve these
breeds or even revive lost populations, e.g. through the use of crosses with
similar breeds. However, the remaining populations are expected to contain
crossbred individuals resulting from introgressions. They are likely to carry
exogenous genes that affect the breed's authenticity on a genomic level. Using
the revived Campine breed as a case study, 289 individuals registered as
purebreds were genotyped on the Illumina BovineSNP50. In addition, genomic
information on the Illumina BovineHD and Illumina BovineSNP50 of ten breeds was
available to assess the current population structure, genetic diversity, and
introgression with phenotypically similar and/or historically related breeds.
Introgression with Holstein and beef cattle genotypes was limited to only a few
farms. While the current population shows a substantial amount of within-breed
variation, the majority of genotypes can be separated from other breeds in the
study, supporting the re-establishment of the Campine breed. The majority of the
population is genetically close to the Deep Red (NL), Improved Red (NL) and
Eastern Belgium Red and White (BE) cattle, breeds known for their historical ties
to the Campine breed. This would support an open herdbook policy, thereby
increasing the population size and consequently providing a more secure future
for the breed.
PMID- 28426823
TI - Observation of sigma-pore currents in mutant hKv1.2_V370C potassium channels.
AB - Current through the sigma-pore was first detected in hKv1.3_V388C channels, where
the V388C mutation in hKv1.3 channels opened a new pathway (sigma-pore) behind
the central alpha-pore. Typical for this mutant channel was inward current at
potentials more negative than -100 mV when the central alpha-pore was closed. The
alpha-pore blockers such as TEA+ and peptide toxins (CTX, MTX) could not reduce
current through the sigma-pore of hKv1.3_V388C channels. This new pathway would
proceed in parallel to the alpha-pore in the S6-S6 interface gap. To see whether
this phenomenon is restricted to hKv1.3 channels we mutated hKv1.2 at the
homologue position (hKv1.2_V370C). By overexpression of hKv1.2_V370C mutant
channels in COS-7 cells we could show typical sigma-currents. The
electrophysiological properties of the sigma-pore in hKv1.3_V388C and
hKv1.2_V370C mutant channels were similar. The sigma-pore of hKv1.2_V370C
channels was most permeable to Na+ and Li+ whereas Cl- and protons did not
influence current through the sigma-pore. Tetraethylammonium (TEA+),
charybdotoxin (CTX) and maurotoxin (MTX), known alpha-pore blockers, could not
reduce current through the sigma-pore of hKv1.2_V370C channels. Taken together we
conclude that the observation of sigma-pore currents is not restricted to Kv1.3
potassium channels but can also be observed in a closely related potassium
channel. This finding could have implications in the treatment of different ion
channel diseases linked to mutations of the respective channels in regions close
to homologue position investigated by us.
PMID- 28426824
TI - Becoming more oneself? Changes in personality following DBS treatment for
psychiatric disorders: Experiences of OCD patients and general considerations.
AB - Does DBS change a patient's personality? This is one of the central questions in
the debate on the ethics of treatment with Deep Brain Stimulation (DBS). At the
moment, however, this important debate is hampered by the fact that there is
relatively little data available concerning what patients actually experience
following DBS treatment. There are a few qualitative studies with patients with
Parkinson's disease and Primary Dystonia and some case reports, but there has
been no qualitative study yet with patients suffering from psychiatric disorders.
In this paper, we present the experiences of 18 patients with Obsessive
Compulsive Disorder (OCD) who are undergoing treatment with DBS. We will also
discuss the inherent difficulties of how to define and assess changes in
personality, in particular for patients with psychiatric disorders. We end with a
discussion of the data and how these shed new light on the conceptual debate
about how to define personality.
PMID- 28426825
TI - Levels of HIV-1 persistence on antiretroviral therapy are not associated with
markers of inflammation or activation.
AB - Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but
both can persist despite clinically effective ART. The relationships among pre
ART and on-ART levels of HIV-1 and activation are incompletely understood, in
part because prior studies have been small or cross-sectional. To address these
limitations, we evaluated measures of HIV-1 persistence, inflammation, T cell
activation and T cell cycling in a longitudinal cohort of 101 participants who
initiated ART and had well-documented sustained suppression of plasma viremia for
a median of 7 years. During the first 4 years following ART initiation, HIV-1 DNA
declined by 15-fold (93%) whereas cell-associated HIV-1 RNA (CA-RNA) fell 525
fold (>99%). Thereafter, HIV-1 DNA levels continued to decline slowly (5% per
year) with a half-life of 13 years. Participants who had higher HIV-1 DNA and CA
RNA before starting treatment had higher levels while on ART, despite suppression
of plasma viremia for many years. Markers of inflammation and T cell activation
were associated with plasma HIV-1 RNA levels before ART was initiated but there
were no consistent associations between these markers and HIV-1 DNA or CA-RNA
during long-term ART, suggesting that HIV-1 persistence is not driving or driven
by inflammation or activation. Higher levels of inflammation, T cell activation
and cycling before ART were associated with higher levels during ART, indicating
that immunologic events that occurred well before ART initiation had long-lasting
effects despite sustained virologic suppression. These findings should stimulate
studies of viral and host factors that affect virologic, inflammatory and
immunologic set points prior to ART initiation and should inform the design of
strategies to reduce HIV-1 reservoirs and dampen immune activation that persists
despite ART.
PMID- 28426826
TI - Link-prediction to tackle the boundary specification problem in social network
surveys.
AB - Diffusion processes in social networks often cause the emergence of global
phenomena from individual behavior within a society. The study of those global
phenomena and the simulation of those diffusion processes frequently require a
good model of the global network. However, survey data and data from online
sources are often restricted to single social groups or features, such as age
groups, single schools, companies, or interest groups. Hence, a modeling approach
is required that extrapolates the locally restricted data to a global network
model. We tackle this Missing Data Problem using Link-Prediction techniques from
social network research, network generation techniques from the area of Social
Simulation, as well as a combination of both. We found that techniques employing
less information may be more adequate to solve this problem, especially when data
granularity is an issue. We validated the network models created with our
techniques on a number of real-world networks, investigating degree distributions
as well as the likelihood of links given the geographical distance between two
nodes.
PMID- 28426827
TI - Correction: Helicobacter pylori bab Paralog Distribution and Association with
cagA, vacA, and homA/B Genotypes in American and South Korean Clinical Isolates.
AB - [This corrects the article DOI: 10.1371/journal.pone.0137078.].
PMID- 28426828
TI - Consumption of fortified infant foods reduces dietary diversity but has a
positive effect on subsequent growth in infants from Sumedang district,
Indonesia.
AB - Stunting and underweight among under-five children in Indonesia are common,
raising public health concerns. Whether inappropriate complementary feeding (CF)
practices compromise optimal growth during late infancy in Indonesia is
uncertain. Therefore we characterized and evaluated CF practices in Indonesian
infants and investigated their relationship with subsequent growth. We enrolled
breastfed infants at 6 months of age (n = 230); and followed them at 9 (n = 202)
and 12 months of age (n = 190). We collected socio-demographic and anthropometric
data and two-day in-home weighed food records. Relations between WHO CF
indicators, sentinel foods, and energy and micronutrient intakes at 9 months and
growth at 12 months were explored using multiple linear regression. Stunting and
underweight increased from 15.8% and 4.4% at 6 months to 22.6% and 10.5% at 12
months, respectively. Median intakes of calcium, iron, zinc, and riboflavin were
below WHO recommendations. Infants consuming fortified infant foods (FIFs) at 9
months had diets with a lower dietary diversity (DD) score (2.3 vs.3.0), energy
density, median energy (250 vs. 310 kcal/d) and protein (6.5 vs. 9.1 g/d) intake
than non-consumers (p<0.01), despite higher intakes of calcium, iron, and
vitamins A and C (p<0.001). Positive relations existed for 9-month consumption of
iron-rich/iron fortified infant foods with length-for-age Z-score (LAZ) at 12
months (beta = 0.22; 95% CI: 0.01, 0.44; P = 0.04), and for fortified infant
foods alone with both LAZ (beta = 0.29; 95% CI: 0.09, 0.48; P = 0.04) and weight
for-age Z-score (beta = 0.14; 95% CI: 0.02, 0.26; P = 0.02) at 12 months. The
positive association of FIFs with subsequent growth may be attributed to their
content of both powdered cow's milk and multi-micronutrient fortificants.
Nonetheless, mothers should not be encouraged to over-rely on FIFs as they reduce
DD.
PMID- 28426829
TI - Joint genetic analysis using variant sets reveals polygenic gene-context
interactions.
AB - Joint genetic models for multiple traits have helped to enhance association
analyses. Most existing multi-trait models have been designed to increase power
for detecting associations, whereas the analysis of interactions has received
considerably less attention. Here, we propose iSet, a method based on linear
mixed models to test for interactions between sets of variants and environmental
states or other contexts. Our model generalizes previous interaction tests and in
particular provides a test for local differences in the genetic architecture
between contexts. We first use simulations to validate iSet before applying the
model to the analysis of genotype-environment interactions in an eQTL study. Our
model retrieves a larger number of interactions than alternative methods and
reveals that up to 20% of cases show context-specific configurations of causal
variants. Finally, we apply iSet to test for sub-group specific genetic effects
in human lipid levels in a large human cohort, where we identify a gene-sex
interaction for C-reactive protein that is missed by alternative methods.
PMID- 28426830
TI - Correction: p16INK4a Expression and Immunologic Aging in Chronic HIV Infection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0166759.].
PMID- 28426831
TI - Representation and reporting of kidney disease in cerebrovascular disease: A
systematic review of randomized controlled trials.
AB - Patients with kidney disease (KD) are at increased risk for cerebrovascular
disease (CVD) and CVD patients with KD have worse outcomes. We aimed to determine
the representation of KD patients in major randomized controlled trials (RCTs) of
CVD interventions. We searched MEDLINE for reports of major CVD trials published
through February 9, 2017. We excluded trials that did not report mortality
outcomes, enrolled fewer than 100 participants, or were subgroup, follow-up, or
post-hoc analyses. Two independent reviewers performed study selection and data
extraction. We included 135 RCTs randomizing 194,977 participants. KD patients
were excluded in 48 (35.6%) trials, but were less likely to be excluded from
trials of class I/II recommended interventions (n = 7; 15.9%; p = 0.001) and more
likely to be excluded in trials with registered protocols (45.5% vs. 22.4%; p =
0.007). Exclusion was lower in trials supported by academic or governmental
grants compared to industry or combined funding (21.2% vs. 42.0% and 47.8%; p =
0.033 and 0.028, respectively). Among trials excluding KD patients, 24 (50.0%)
used serum creatinine, 7 (14.6%) used estimated glomerular filtration rate or
creatinine clearance, 7 (14.6%) used renal replacement therapy, and 19 (39.6%)
used non-specific kidney-related criteria. Only 4 (3.0%) trials reported baseline
renal function. No trials prespecified or reported subgroup analyses by baseline
renal function. Although 19 (14.1%) trials reported the incidence of acute kidney
injury, no trial examined adverse event rates according to renal function. In
summary, more than one third of major CVD trials excluded patients with KD,
primarily based on serum creatinine or non-specific criteria, and outcomes were
not stratified by renal parameters. Therefore, purposeful efforts to increase
inclusion of KD patients in CVD trials and evaluate the impact of renal function
on efficacy and safety are needed to improve the quality of evidence for
interventions in this vulnerable population.
PMID- 28426833
TI - Correction: Modulation of behaviour and virulence of a high alginate expressing
Pseudomonas aeruginosa strain from cystic fibrosis by oral commensal bacterium
Streptococcus anginosus.
AB - [This corrects the article DOI: 10.1371/journal.pone.0173741.].
PMID- 28426832
TI - A systematic review of pragmatic language interventions for children with autism
spectrum disorder.
AB - There is a need for evidence based interventions for children with autism
spectrum disorder (ASD) to limit the life-long, psychosocial impact of pragmatic
language impairments. This systematic review identified 22 studies reporting on
20 pragmatic language interventions for children with ASD aged 0-18 years. The
characteristics of each study, components of the interventions, and the
methodological quality of each study were reviewed. Meta-analysis was conducted
to assess the effectiveness of 15 interventions. Results revealed some promising
approaches, indicating that active inclusion of the child and parent in the
intervention was a significant mediator of intervention effect. Participant age,
therapy setting or modality were not significant mediators between the
interventions and measures of pragmatic language. The long-term effects of these
interventions and the generalisation of learning to new contexts is largely
unknown. Implications for clinical practice and directions for future research
are discussed.
PMID- 28426834
TI - Acceptability of an open-label wait-listed trial design: Experiences from the
PROUD PrEP study.
AB - BACKGROUND: PROUD participants were randomly assigned to receive pre-exposure
prophylaxis (PrEP) immediately or after a deferred period of one-year. We report
on the acceptability of this open-label wait-listed trial design. METHODS:
Participants completed an acceptability questionnaire, which included categorical
study acceptability data and free-text data on most and least liked aspects of
the study. We also conducted in-depth interviews (IDI) with a purposely selected
sub-sample of participants. RESULTS: Acceptability questionnaires were completed
by 76% (415/544) of participants. After controlling for age, immediate-group
participants were almost twice as likely as deferred-group participants to
complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the
majority of participants in both groups found the wait-listed design acceptable
when measured by satisfaction of joining the study, intention to remain in the
study, and interest in joining a subsequent study. However, three-quarters
thought that the chance of being in the deferred-group might put other volunteers
off joining the study. In free-text responses, data collection tools were the
most frequently reported least liked aspect of the study. A fifth of deferred
participants reported 'being deferred' as the thing they least liked about the
study. However, more deferred participants disliked the data collection tools
than the fact that they had to wait a year to access PrEP. Participants in the
IDIs had a good understanding of the rationale for the open-label wait-listed
study design. Most accepted the design but acknowledged they were, or would have
been, disappointed to be randomised to the deferred group. Five of the 25
participants interviewed reported some objection to the wait-listed design.
CONCLUSION: The quantitative and qualitative findings suggest that in an
environment where PrEP was not available, the rationale for the wait-listed trial
design was well understood and generally acceptable to most participants in this
study.
PMID- 28426835
TI - Outcomes from a cohort of patients with acute kidney injury subjected to
continuous venovenous hemodiafiltration: The role of negative fluid balance.
AB - BACKGROUND: Several factors influence the outcomes in acute kidney injury (AKI),
especially in intensive care unit (ICU) patients. In this scenario, continuous
renal replacement therapies (CRRT) are used to control metabolic derangements and
blood volume. Knowing this fact, it may be possible to change the course of the
disease and decrease the high mortality rate observed. Thus, we aimed to evaluate
the main risk factors for death in AKI patients needing CRRT. RESULTS: This was a
prospective, observational cohort study of ICU patients (N = 183) with AKI who
underwent continuous venovenous hemodiafiltration (CVVHDF) as their initial
dialysis modality choice. The patients were predominantly male (62.8%) and their
median age was 65 (55-76) years. The most frequent comorbidities were
cardiovascular disease (39.3%), hypertension (32.8%), diabetes (24%), and
cirrhosis (20.7%). The main cause of AKI was sepsis (52.5%). At beginning of
CVVHDF, 152 patients (83%) were using vasopressors. The median SAPS 3 and SOFA
score at ICU admission was 61 (50-74) and 10 (7-12), respectively. The dialysis
dose delivered was 33.2 (28.9-38.7) ml/kg/h. The median time between ICU
admission and CVVHDF initiation was 2 (1-4) days. The median cumulative fluid
balance during the CVVHDF period was -1838 (-5735 +2993) ml. The mortality rate
up to90 days was 58%. The independent mortality risk factors in propensity score
model were: chronic obstructive pulmonary disease (OR = 3.44[1.14-10.4; p =
0.028]), hematologic malignancy (OR = 5.14[1.66-15.95; p = 0.005]), oliguria (OR
= 2.36[1.15-4.9; p = 0.02]), positive daily fluid balance during CVVHDF (OR =
4.55[2.75-13.1; p<0.001]), and total SOFA score on first dialysis day (OR =
1.27[1.12-1.45; p<0.001]). CONCLUSIONS: Dialysis-related factors may influence
the outcomes. In our cohort, positive daily fluid balance during CRRT was
associated with lower survival. Multicenter, randomized studies are needed to
assess fluid balance as a primary outcome to define the best strategy in this
patient population.
PMID- 28426836
TI - Facework and trust in facilitating health-focused housing interventions.
AB - The link between housing and health is of increasing importance in the UK policy
and practice context, in which poor housing is often accepted as a social
determinant of poor health. Service users' experiences of, and outcomes from, a
British information, advice, support and guidance service focused on the
relationship between housing problems and health issues were explored. This
service facilitates home improvements for privately housed residents with housing
issues exacerbating or causing health problems. In-depth interviews with
occupants of 15 households which received the service were completed. The
findings highlighted three key themes: the need for participants' person-home fit
to reflect and adapt to any degeneration in health conditions; the facilitation
of knowledge and access to housing and other support available to them; and
perceived positive health and wellbeing outcomes from the receipt of personalised
advice and support. The delivery of these outcomes by a named officer of the
service team, and the relationship this developed with the service user, are
considered within the context of facework, whereby they became a trusted source
of guidance in navigating a complex system of assistance. These findings add to
the growing knowledge base on housing and health, and also highlight the critical
importance of a facework approach in allowing service users to navigate complex
systems in order to achieve beneficial outcomes.
PMID- 28426837
TI - The high prevalence of HPV and HPV16 European variants in cervical and anal
samples of HIV-seropositive women with normal Pap test results.
AB - Human Immunodeficiency Virus (HIV)-seropositive women are more likely to have
anogenital cancer, and high risk-HPV (HR-HPV) infection is the main associated
factor. Between August 2013 and December 2015, we conducted a descriptive study
to determine the HPV genotypes and HPV16 variants in cervical and anal samples of
HIV-seropositive women with a normal Pap test. The viral DNA was amplified by PCR
using the PGMY09/11 set of primers. Reverse line blot (RLB), restriction fragment
length polymorphism (RFLP) and sequencing assays were used to determine the HPV
genotypes. HPV16 variants were identified by gene sequencing. We found a high
frequency of HR-HPV (60.3%; 76/126) at the anogenital site among HIV-seropositive
women and without association with anal intercourse. HPV16 and European variant
predominated among the HR-HPV. Mixed infections with at least three different HPV
types were common, particularly at the anal site. CD4+ T-cell counts below 500
cells/mm3, a HIV viral load above 50 copies/mL and an age of 18 to 35 years old
were all related to HPV anal infection. Our study showed a high frequency of HR
HPV in both cervical and anal sites of women with negative cytology belonging to
a risk group for the development of anogenital cancer.
PMID- 28426839
TI - Medical History in the Hellenic Journal of Nuclear Medicine.
AB - The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th
anniversary end of 2017. On board of the editorial team since 2003, this journal
has influenced me like a good friend over the many past years. From time to time,
the journal has published interesting and valuable historical notes. They show
that nuclear medicine has a history and that medicine is its basis. They also
teach us today, and some of the ancient perspectives and approaches are still
valid. The reader of HJNM may be interested in these historical contributions, as
they are timeless. Therefore, it was our idea to summarize these in the following
pages. Where there is a link to the free article, this is noted. Upon opening all
articles, you will find out that these are a book or so of its own. In thanks to
the editor-in-chief of the Journal for his continuing support on the historical
section. Below we refer to the historical papers of the Journal: History of
Nuclear Medicine. Nuclear Medicine and History of Science and Philosophy: Atomic
Theory of the Matter. G.N. Sfakianakis, 2001; 4(3); 155-60. Editorial. Pioneers
of nuclear medicine, Madame Curie. P.C. Grammaticos. 2004; 7(1); 29-30.
http://nuclmed.web.auth.gr/ magazine/eng/jan04/editorial.htm Editor's note.
Hippocrates' Oath. The editor. 2004; 7(1); 31. Editorial. Useful known and
unknown views of the father of modern medicine, Hippocrates and his teacher
Democritus. P. Grammaticos, A. Diamantis. 2008; 11(1): 2-4.
http://nuclmed.web.auth.gr/magazine/eng/jan08/2.pdf Special Article. The
contribution of Maria Sklodowska-Curie and Pierre Curie to Nuclear and Medical
Physics. A hundred and ten years after the discovery of radium. A. Diamantis, E.
Magiorkinis, 2008; 11(1): 33-8. http://nuclmed.web.auth.gr/magazine/
eng/jan08/33.pdf Brief Historical Review. Lymphatic system and
lymphoscintigraphy. P. Valsamaki. 2009; 12(1): 87-89. http://nuclmed.web.
auth.gr/magazine/eng/jan09/89.pdf (In Greek) Historical Review. The philosophic
and biological views of the "atomic" philosophers, Leucippus and Democritus. E.
Magiorkinis. A. Beloukas, A. Diamantis. 2010; 13(2): 111-117.
http://nuclmed.web.auth.gr/magazine/eng/may10/9.pdf Correspondence. Neuroimaging
in mild traumatic brain injury and M. Ravel's injury. A. Otte. 2012; 15(1): 76.
http://nuclmed. web.auth.gr/magazine/eng/jan12/3.pdf Selected Brief
Contributions. The "atomic theory" of Leucippus, and its impact on medicine
before Hippocrates. G. Tsoucalas, K. Laios et al. 2013; 16(1): 68-9.
http://nuclmed.web.auth.gr/magazine/eng/jan13/72.pdf Selected Brief
Contributions. Computed tomography alone reveals the secrets of ancient mummies
in medical archaeology. A. Otte, T. Thieme et al. 2013; 16(2): 148-9.
http://nuclmed.web.auth.gr/magazine/eng/may13/70.pdf Editorial. The timeless
influence of Hippocratic ideas on diet, salicylates and personalized medicine.
T.C. Karagiannis. 2014; 17(1): 2-6.
http://nuclmed.web.auth.gr/magazine/eng/jan14/1.pdf Historical Article. The
physician who first applied radiotherapy, Victor Despeignes, on 1896. M.
Sgantzos, G. Tsoucalas et al. 2014; 17(1): 45-6.
http://nuclmed.web.auth.gr/magazine/eng/jan14/11.pdf Original Articles. Medical
practice applied in the ancient Asclepeion in Kos island. M. Mironidou
Tzouveleki, P.M. Tzitzis. 2014; 17(3): 167-70.
http://www.nuclmed.web.auth.gr/magazine/eng/sept14/3.pdf Special Historical
Article. How a tertiary medical nuclear medicine department at the Himalayan area
in India can be established and function in an exemplary manner. Basic rules
revisited. V.K. Dhingra, S. Saini et al. 2015; 18(3): 252-6. http://
nuclmed.web.auth.gr/magazine/eng/sept15/13.pdf Historical and Commentary Note.
Johann Sebastian Bach's "Goldberg variations" to treat insomnia from renal
lithiasis pain. Sleep research in Nuclear Medicine. A. Otte. 2016; 19(1): 13-4.
http://nuclmed.web.auth.gr/magazine/eng/jan16/06.pdf Historical Review. The first
medical ethics and deontology in Europe as derived from Greek mythology. M.K.
Konstantinidou. 2016; 19(2): 155
8.http://nuclmed.web.auth.gr/magazine/eng/may16/11.pdf Historical-Technical
Article. The beginning of using X-rays and the evolution of equipment for the
treatment of ocular cancer. K. Laios, M. Zozoglou. 2017; 20(1): Ahead of print.
And hopefully many more to follow!
PMID- 28426838
TI - A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected
epithelial cells.
AB - Type III secretion system 1 (T3SS1) is used by the enteropathogen Salmonella
enterica serovar Typhimurium to establish infection in the gut. Effector proteins
translocated by this system across the plasma membrane facilitate invasion of
intestinal epithelial cells. One such effector, the inositol phosphatase SopB,
contributes to invasion and mediates activation of the pro-survival kinase Akt.
Following internalization, some bacteria escape from the Salmonella-containing
vacuole into the cytosol and there is evidence suggesting that T3SS1 is expressed
in this subpopulation. Here, we investigated the post-invasion role of T3SS1,
using SopB as a model effector. In cultured epithelial cells, SopB-dependent Akt
phosphorylation was observed at two distinct stages of infection: during and
immediately after invasion, and later during peak cytosolic replication. Single
cell analysis revealed that cytosolic Salmonella deliver SopB via T3SS1. Although
intracellular replication was unaffected in a SopB deletion mutant, cells
infected with DeltasopB demonstrated a lack of Akt phosphorylation, earlier time
to death, and increased lysis. When SopB expression was induced specifically in
cytosolic Salmonella, these effects were restored to levels observed in WT
infected cells, indicating that the second wave of SopB protects this infected
population against cell death via Akt activation. Thus, T3SS1 has two, temporally
distinct roles during epithelial cell colonization. Additionally, we found that
delivery of SopB by cytosolic bacteria was translocon-independent, in contrast to
canonical effector translocation across eukaryotic membranes, which requires
formation of a translocon pore. This mechanism was also observed for another
T3SS1 effector, SipA. These findings reveal the functional and mechanistic
adaptability of a T3SS that can be harnessed in different microenvironments.
PMID- 28426840
TI - Multimodality-multiparametric brain tumors evaluation.
AB - Brain tumors represent a vast group of lesions, originating from different
neuronal cells with different degrees of aggressiveness. Despite some
technological advances either pre or post-treatment, these tumors may share
similar imaging findings and properties, rendering diagnosis/prognosis, an
ambiguous process. Gadolinium-enhanced magnetic resonance imaging remains the
gold standard for providing detailed morphologic information, but presents
several limitations due to the overlap of findings, in cases such as progressive
tumor and post-radiation related effects. Tumor cellularity, vascularity,
proliferative activity, metabolic and functional profiles are a few of many
characteristics that may further support tumor classification, but cannot be
assessed by conventional imaging alone. We review the aforementioned factors and
indicate how they improve tumor characterization and grading in order to design
the optimal treatment strategy and better evaluate post treatment efficacy.
PMID- 28426841
TI - Bilateral Retinal Whitening in a Hospitalized Patient.
PMID- 28426842
TI - Association of Patient Age With Outcomes of Current-Era, Large-Scale Screening
Mammography: Analysis of Data From the National Mammography Database.
PMID- 28426843
TI - Understanding the Risks and Harms of Management of Incidental Thyroid Nodules: A
Review.
AB - Importance: Incidental thyroid nodules are defined as nodules originally detected
in a patient with no thyroid-related clinical symptoms, examination findings, or
suspected thyroid disease. Medical imaging for diseases in the neck, chest, and
spine is a common source of incidental thyroid nodules. They are easily detected
but poorly characterized. The next step is to decide whether the incidental
thyroid nodule should be further evaluated with ultrasonography. Observations:
Indiscriminate workup of incidental thyroid nodules with ultrasonography is not
cost-effective and is potentially harmful. Although the concern for malignant
neoplasms drives workup, the risk for poor outcomes without evaluation is
minimal. The rate of malignant tumors in patients with 1 or more thyroid nodules
larger than 5 mm is only 1.6%, and most small thyroid cancers are indolent.
Substantial evidence suggests that a reservoir of thyroid cancers does not
progress, and workup after detection with imaging leads to epidemiologic
overdiagnosis. Finally, a significant proportion of patients with benign nodules
have cytologic results that are not definitive and require lobectomy. Evidence
based recommendations for incidental thyroid nodules detected at computed
tomography, magnetic resonance imaging, nuclear medicine studies, and
extrathyroidal ultrasonography include selection criteria for nodule workup based
on suspicious imaging findings, patient age, and nodule size. In the absence of
clinical risk factors or suspicious imaging findings, workup with dedicated
thyroid ultrasonography is only recommended for nodules at least 1.5 cm in
patients 35 years or older and for nodules at least 1.0 cm in patients younger
than 35 years. Conclusions and Relevance: Only a few select incidental thyroid
nodules require further evaluation with ultrasonography based on recommendations
that aim to diagnose clinically significant thyroid cancers while reducing
unnecessary workup and provide guidance for clinical practice.
PMID- 28426844
TI - Beyond Medication Reconciliation: The Correct Medication List.
PMID- 28426846
TI - Affordability of Cancer Drugs in Sub-Saharan Africa: Effects of Pricing on
Needless Loss of Life.
PMID- 28426845
TI - HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for
Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial.
AB - Importance: Glioblastoma is an incurable tumor, and the therapeutic options for
patients are limited. Objective: To determine whether the systemic administration
of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells
(VSTs) is safe and whether these cells have antiglioblastoma activity. Design,
Setting, and Participants: In this open-label phase 1 dose-escalation study
conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas
Children's Hospital, patients with progressive HER2-positive glioblastoma were
enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was
10 weeks to 29 months (median, 8 months). Interventions: Monotherapy with
autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus
and genetically modified to express HER2-CARs with a CD28.zeta-signaling
endodomain (HER2-CAR VSTs). Main Outcomes and Measures: Primary end points were
feasibility and safety. The key secondary end points were T-cell persistence and
their antiglioblastoma activity. Results: A total of 17 patients (8 females and 9
males; 10 patients >=18 years [median age, 60 years; range, 30-69 years] and 7
patients <18 years [median age, 14 years; range, 10-17 years]) with progressive
HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR
VSTs (1 * 106/m2 to 1 * 108/m2) without prior lymphodepletion. Infusions were
well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected
in the peripheral blood for up to 12 months after the infusion by quantitative
real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7
children), 1 had a partial response for more than 9 months, 7 had stable disease
for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients
with stable disease are alive without any evidence of progression during 24 to 29
months of follow-up. For the entire study cohort, median overall survival was
11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5
months (95% CI, 17.2-34.6 months) from diagnosis. Conclusions and Relevance:
Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical
benefit for patients with progressive glioblastoma. Further evaluation of HER2
CAR VSTs in a phase 2b study is warranted as a single agent or in combination
with other immunomodulatory approaches for glioblastoma.
PMID- 28426847
TI - Safety and Efficacy of Bilateral Submental Cryolipolysis With Quantified 3
Dimensional Imaging of Fat Reduction and Skin Tightening.
AB - Importance: Cryolipolysis is a popular, well-tolerated nonsurgical procedure that
uses controlled cooling to selectively destroy fat cells. Central submental
cryolipolysis has been reported to be safe and effective, but many patients would
benefit from extending this treatment over the entire submental region.
Objective: To investigate the safety and efficacy of cryolipolysis for reduction
of lateral and central submental fat. Design, Setting, and Participants: The
study population consisted of 14 participants who were treated from January 22 to
June 30, 2016, in the lateral and central submental area to reduce unwanted
subcutaneous fat. A small-volume cup applicator was used to administer 2
cryolipolysis treatments, delivered in 45-minute treatment cycles in 2 sessions.
For the first treatment session, all participants received bilateral treatments
with approximately 20% overlap of the treatment area. At the 6-week follow-up
visit, participants were reassessed to determine whether they would benefit from
a second treatment and to determine the number of cycles needed to achieve the
optimal aesthetic result, and then they were treated a second time. Main Outcomes
and Measures: Participant surveys assessed tolerability and treatment
satisfaction at 12 weeks following the second treatment. Clinicians monitored
adverse events to assess safety. Caliper measurements were recorded to assess fat
thickness reduction. Treatment efficacy was objectively evaluated using 2
dimensional and 3-dimensional imaging. Results: Among the 14 participants (12
women and 2 men; mean [SD] age, 50.5 [10.4] years), the adverse effects of the
procedure were typically mild and included numbness and tingling, which resolved
without intervention by the final 12-week follow-up visit. An independent review
of digital photographs revealed an 81.0% (95% CI, 65.9%-91.4%; P = .02) correct
identification rate (34 of 42 images) of the pretreatment and posttreatment
images. Caliper measurements demonstrated a mean (SD) fat layer reduction of 2.3
(0.8) mm (range, 0.7-3.5 mm). Three-dimensional imaging revealed a mean (SD)
reduction in fat volume of 4.82 (11.42) cm3 (from a reduction of 32.69 cm3 to an
increase of 13.85 cm3), in skin surface area of 1.29 (1.42) cm2 (from a reduction
of 3.18 cm2 to an increase of 0.99 cm2), and in fat thickness of 3.77 (3.59) mm
(from of reduction of 13.10 mm to an increase of 0.47 mm). Results of participant
surveys indicated that 13 participants (93%) were satisfied with the
cryolipolysis treatment. Conclusions and Relevance: Although safe and efficacious
central submental cryolipolysis has been reported, this is the first clinical
study of cryolipolysis for treatment of the entire submental area using
overlapping bilateral treatments and a shorter treatment duration. The study
demonstrates that bilateral submental cryolipolysis is well tolerated and
produces visible and significant fat layer reduction. Level of Evidence: 4.
PMID- 28426848
TI - Differences in Survival With Surgery and Postoperative Radiotherapy Compared With
Definitive Chemoradiotherapy for Oral Cavity Cancer: A National Cancer Database
Analysis.
AB - Importance: Because locally advanced oral cavity squamous cell carcinoma (OCSCC)
is often treated with surgery followed by postoperative radiotherapy (S+PORT),
the effectiveness of organ preservation with concurrent chemoradiotherapy (CRT)
remains unclear. Objective: To compare the differences in survival between
patients with locally advanced OCSCC treated with S+PORT or CRT. Design, Setting,
and Participants: Using the National Cancer Database, this study compared 6900
patients with stage III to IVA OCSCC treated with S+PORT and CRT from 2004
through 2012 at academic and community-based cancer clinics. Comparisons were
made using Kaplan-Meier methods and Cox proportional hazards regression models
using the entire cohort and a propensity score-matched cohort of 2286 patients.
Main Outcomes and Measures: Overall survival (OS). Results: Of the 6900 study
patients, 4809 received S+PORT (3080 male [64.0%] and 1792 [36.0%] female) and
2091 received CRT (1453 male [69.5%] and 638 [30.5%] female). Median follow-up
for the entire group was 23.0 months overall but was shorter for patients
receiving CRT (17.3-month) vs S+PORT (25.6 months). Patients receiving CRT were
more likely to be older than 60 years, treated before 2007, live within 10 miles
of the treating facility, treated at nonacademic centers, have more
comorbidities, have T3 to T4a tumors, and have N2a to N2c nodal disease.
Propensity score matching identified cohorts of patients with similar clinical
variables. S+PORT was associated with improved survival among all patients (3
year OS: 53.9% for S+PORT vs 37.8% for CRT; difference = 16.1%; 95% CI, 13.6%
18.6%) and in the propensity score-matched cohort (3-year OS: 51.8% for S+PORT vs
39.3% for CRT; difference = 11.9%; 95% CI, 7.8%-16.0%). S+PORT was associated
with improved survival among patients with T3 to T4a tumors (3-year OS: 49.7% for
S+PORT vs 36.0% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) but was not
associated with improved survival among patients with T1 to T2 tumors (3-year OS:
59.1% for S+PORT vs 53.5% for CRT; difference = 5.6%; 95% CI, -3.1% to 14.3%).
Conclusions and Relevance: Compared with CRT, S+PORT was associated with improved
survival for locally advanced OCSCCs, especially in T3 to T4a disease. These data
support the use of surgery as the initial treatment modality for operable OCSCCs.
PMID- 28426849
TI - Effect of Adalimumab on Visual Functioning in Patients With Noninfectious
Intermediate Uveitis, Posterior Uveitis, and Panuveitis in the VISUAL-1 and
VISUAL-2 Trials.
AB - Importance: Adalimumab was recently approved for the treatment of noninfectious
intermediate uveitis, posterior uveitis, and panuveitis. Objective: To assess the
effect of adalimumab on the visual functioning and quality of life in patients
with corticosteroid-dependent noninfectious intermediate uveitis, posterior
uveitis, and panuveitis. Design: A post hoc analysis of clinical trials of adults
with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate
uveitis, posterior uveitis, and panuveitis was conducted in the United States,
Canada, Europe, Israel, Australia, Latin America, and Japan. A total of 217
patients (110 adalimumab, 107 placebo) in VISUAL-1 and 226 patients (115
adalimumab, 111 placebo) in VISUAL-2 were studied using intent-to-treat analyses.
The clinical trials were conducted between August 10, 2010, and May 14, 2015.
Interventions: In VISUAL-1 and VISUAL-2, patients were randomized to receive
adalimumab, 80-mg, subcutaneous loading dose followed by 40 mg every other week
or placebo for 80 weeks. All patients underwent prednisone tapering, with
patients in VISUAL-1 receiving an initial prednisone burst. Main Outcomes and
Measures: The 25-item National Eye Institute Vision Function Questionnaire (NEI
VFQ-25) composite score questionnaire assessed the impact of visual impairment
from the patient's perspective; scores on the questionnaire range from 0 to 100,
with higher scores indicating better vision-related quality of life. The change
in NEI VFQ-25 from best state achieved prior to week 6 (VISUAL-1) and from
baseline state (VISUAL-2) to the final or early termination visit was determined
in each group and statistically compared using analysis of variance. The temporal
effects of adalimumab and placebo on NEI VFQ-25 were investigated using a
longitudinal model. Results: Of the 217 patients in VISUAL-1, 124 (57.1%) were
women; the mean (SD) age was 42.7 (14.9) years. Of the 226 patients in VISUAL-2,
138 (61.1%) were women; the mean (SD) age was 42.5 (13.4). In VISUAL-1, the
change from final score to best score in NEI VFQ-25 was -1.30 for adalimumab and
5.50 for placebo-a difference of 4.20 (95% CI, 1.04 to 7.36; P = .01) associated
with adalimumab compared with placebo. In VISUAL-2, the change from baseline NEI
VFQ-25 was 3.36 for adalimumab and 1.24 for placebo-a difference of 2.12 (95% CI,
-0.81 to 5.04; P = .16). In both trials, the longitudinal models showed a
significant difference in NEI VFQ-25 between adalimumab and placebo of 3.07 (95%
CI, 2.09 to 4.06; P < .001) and 4.66 (95% CI, 0.05 to 9.26; P = .048) in the
VISUAL-1 (74.15 vs 71.08) and VISUAL-2 (82.39 vs 77.73) trials, respectively.
Conclusions and Relevance: This post hoc analysis suggests that adalimumab is
associated with statistically significant and clinically meaningful improvements
in patient-reported visual functioning for patients with noninfectious
intermediate uveitis, posterior uveitis, and panuveitis. Trial Registration:
clinicaltrials.gov Identifiers: NCT01138657 (VISUAL-1) and NCT01124838 (VISUAL
2).
PMID- 28426850
TI - Second Primary Malignant Neoplasms and Survival in Adolescent and Young Adult
Cancer Survivors.
AB - Importance: Although the increased incidence of second primary malignant
neoplasms (SPMs) is a well-known late effect after cancer, few studies have
compared survival after an SPM to survival of the same cancer occurring as first
primary malignant neoplasm (PM) by age. Objective: To assess the survival impact
of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that
of pediatric (<15 years) and older adult (>=40 years) patients with the same
SPMs. Design, Setting, and Participants: This was a population-based,
retrospective cohort study of patients with cancer in 13 Surveillance,
Epidemiology and End Results regions in the United States diagnosed from 1992 to
2008 and followed through 2013. Data analysis was performed between June 2016 and
January 2017. Main Outcomes and Measures: Five-year relative survival was
calculated overall and for each cancer occurring as a PM or SPM by age at
diagnosis. The impact of SPM status on cancer-specific death was examined using
multivariable Cox proportional hazards regression. Results: A total of 15 954
pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14
cancers occurring as a PM or SPM were included. Overall, 5-year survival after an
SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older
adults compared with a PM at the same age. For the most common SPMs in AYAs, the
absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin
lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid
carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was
significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma,
non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central
nervous system cancer. Adolescents and young adults with secondary Hodgkin
lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1
3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]);
and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival
compared with AYAs with the same PMs. Conclusion and Relevance: The adverse
impact of SPMs on survival is substantial for AYAs and may partially explain the
relative lack of survival improvement in AYAs compared with other age groups. The
impact of a particular SPM diagnosis on survival may inform age-specific
prevention, screening, treatment, and survivorship recommendations.
PMID- 28426851
TI - Unilateral Hearing Loss and Otorrhea.
PMID- 28426853
TI - A Cautious but Optimistic Opinion of Submental Cryolipolysis.
PMID- 28426852
TI - An Outbreak of Endogenous Fungal Endophthalmitis Among Intravenous Drug Abusers
in New England.
AB - Importance: Intravenous drug abuse (IVDA) is a known risk factor for endogenous
fungal endophthalmitis (EFE), a severe intraocular infection caused by
hematogenous seeding of mycotic organisms to the eye. Reporting significant
increases in heroin-related deaths since 2014, the New England region is in the
midst of an opioid crisis that has led to a substantial increase in patients at
risk for this vision-threatening disease. Objective: To present an update on
characteristics, management, and visual outcomes in patients with EFE. Design,
Setting, and Participants: Medical records review was initiated on July 1, 2016,
evaluating all patients with EFE referred to New England Eye Center at Tufts
Medical Center, a tertiary care ophthalmology practice distributed throughout
Massachusetts, from May 1, 2014, to May 1, 2016. Patients with a history of IVDA
and culture-proven or clinical evidence of fungal endophthalmitis were included.
Exposures: Intravenous drug use. Main Outcomes and Measures: Patient
demographics, comorbidities, presenting symptoms and vision, vitreoretinal
findings, treatment regimens, culture data, and final visual acuities. Results:
Ten patients (5 women) with IVDA-related EFE were identified between May 1, 2014,
and May 1, 2016-an increase from 3 patients treated from May 2012 to April 2014.
The mean (SD) patient age was 34 (11) years (range, 24-60 years). Presenting
visual acuities ranged from 20/25 to hand motion. The most common presenting
symptoms were floaters (n = 8), reduced vision (n = 6), and pain (n = 5). Initial
treatment included systemic antifungals in all patients and intravitreal
antifungals in 9 eyes. Five patients required pars plana vitrectomy for worsening
vitritis. The most commonly isolated pathogen was Candida albicans in 20% of the
patients. Final visual acuity ranged from 20/40 to 20/300. Conclusions and
Relevance: The data provided in this report suggest that EFE represents severe
end organ damage associated with IVDA and portends poor visual outcomes. Health
care professionals must maintain a high suspicion for EFE, as patients are
typically ambulatory on presentation without systemic signs of infection.
PMID- 28426854
TI - Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal
Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid
Hemorrhage (STASH) Trial: Erratum.
PMID- 28426855
TI - Journal Club: Outpatient Cervical and Lumbar Spine Surgery is Feasible and Safe:
A Consecutive Single Center Series of 1449 Patients: Erratum.
PMID- 28426856
TI - Adjunctive Oral Voriconazole Treatment of Fusarium Keratitis: A Secondary
Analysis From the Mycotic Ulcer Treatment Trial II.
AB - Importance: Fusarium keratitis is common and often results in poor outcomes. No
new treatments since natamycin have become available. Objective: To explore the
role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis.
Design, Setting, and Participants: In this prespecified subgroup analysis of a
multicenter, double-masked, placebo-controlled randomized clinical trial, 240
patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and
Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco,
who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or
worse were randomized to receive oral voriconazole vs placebo. Enrollment started
May 24, 2010, and the last patient study visit was November 23, 2015. All
patients received topical voriconazole, 1%, and after the results of the Mycotic
Ulcer Treatment Trial (MUTT) II became available, topical natamycin, 5%, was
added for all patients. Data analysis was performed from September 2 to October
28, 2016. Main Outcomes and Measures: The primary outcome of the trial was the
rate of corneal perforation or the need for therapeutic penetrating keratoplasty.
Secondary outcomes included rate of reepithelialization, best spectacle-corrected
visual acuity, and infiltrate or scar size at 3 months. Results: Of the 240 study
participants, 72 (30.4%) were culture positive for Fusarium species (41 [56.9%]
male and 31 [43.1%] female; median [interquartile range] age, 50 [45-57] years).
Of these, 33 (45.8%) were randomized to oral voriconazole and 39 (54.2%) to
placebo. Fusarium ulcers randomized to oral voriconazole had a 0.43-fold
decreased hazard of perforation or therapeutic penetrating keratoplasty compared
with placebo after controlling for baseline infiltrate depth (95% CI, 0.22-fold
to 0.84-fold; P = .01). Multiple linear regression revealed a 1.89-mm decreased
infiltrate and/or scar size at 3 weeks (95% CI, -2.69 to -1.09 mm; P < .001) and
a 0.83-mm decreased infiltrate and/or scar size at 3 months after correcting for
baseline values (95% CI, -1.33 to -0.32 mm; P = .001) in eyes randomized to oral
voriconazole vs placebo. Eyes treated with oral voriconazole also had a mean 0.29
decreased logMAR (improved) (Snellen equivalent 20/40) visual acuity at 3 months
after controlling for baseline visual acuity, although this finding was not
statistically significant (95% CI, -0.57 to 0.002; P = .052). Conclusions and
Relevance: Although MUTT II could not find a benefit for all corneal ulcers,
Fusarium keratitis may benefit from the addition of oral voriconazole to topical
natamycin, and physicians should consider prescribing oral voriconazole in these
cases. Trial Registration: clinicaltrials.gov Identifier: NCT00996736.
PMID- 28426857
TI - Spectacle Wear Among Children in a School-Based Program for Ready-Made vs Custom
Made Spectacles in India: A Randomized Clinical Trial.
AB - Importance: Uncorrected refractive errors are the most common cause of visual
impairment in children despite correction being highly cost-effective. Objective:
To determine whether less expensive ready-made spectacles produce rates of
spectacle wear at 3 to 4 months comparable to those of more expensive custom-made
spectacles among eligible school-aged children. Design, Setting, and
Participants: This noninferiority, double-masked, randomized clinical trial
recruited children aged 11 to 15 years from January 12 through July 31, 2015,
from government schools in urban and periurban areas surrounding Bangalore,
India. Follow-up occurred from August 1 through September 31, 2015. Participants
met the following eligibility criteria for ready-made spectacles: failed vision
screening at the 6/9 level in each eye; refraction was indicated; acuity improved
with correction by 2 or more lines in the better-seeing eye; the corrected acuity
with the spherical equivalent was not more than 1 line less than with full
correction; anisometropia measured less than 1.0 diopter; and an appropriate
frame was available. Interventions: Eligible children were randomized to ready
made or custom-made spectacles. Main Outcomes and Measures: Proportion of
children wearing their spectacles at unannounced visits 3 to 4 months after the
intervention. Results: Of 23 345 children aged 11 to 15 years who underwent
screening, 694 had visual acuity of less than 6/9 in both eyes, and 535 underwent
assessment for eligibility. A total of 460 children (227 female [49.3%] and 233
male [50.7%]; mean [SD] age, 13.4 [1.3] years) were eligible for ready-made
spectacles (2.0% undergoing screening and 86.0% undergoing assessment) and were
randomized to ready-made (n = 232) or custom-made (n = 228) spectacles. Follow-up
rates at 3 to 4 months were similar (184 [79.3%] in the ready-made group and 178
[78.1%] in the custom-made group). Rates of spectacle wear in the 2 arms were
similar among 139 of 184 children (75.5%) in the ready-made arm and 131 of 178
children (73.6%) in the custom-made arm (risk difference, 1.8%; 95% CI, -7.1% to
10.8%). Conclusions and Relevance: Most children were eligible for ready-made
spectacles, and the proportion wearing ready-made spectacles was not inferior to
the proportion wearing custom-made spectacles at 3 to 4 months. These findings
suggest that ready-made spectacles could substantially reduce costs for school
based eye health programs in India without compromising spectacle wear, at least
in the short term. Trial Registration: isrctn.com Identifier: ISRCTN14715120.
PMID- 28426858
TI - Improving More Than Just Vision in Noninfectious Uveitis.
PMID- 28426861
TI - Additional Data for Figures.
PMID- 28426864
TI - A Novel 3-Dimensional Printable Bone Substitute.
PMID- 28426865
TI - Decompressive Craniectomy for Traumatic Intracranial Hypertension.
PMID- 28426866
TI - Cognitive Fountain of Youth.
PMID- 28426867
TI - Stem Cell Transplantation Helps Alleviate Spinal Cord Injury Sequelae in Mice.
PMID- 28426868
TI - How Do We Decide? Macaque Orbitofrontal Cortex Neurons Encode Available Options
Independently in Subjective Decisions.
PMID- 28426869
TI - Expression Profiling of Nonpolar Lipids in Meibum From Patients With Dry Eye: A
Pilot Study.
AB - Purpose: The purpose of this investigation was to characterize differentially
expressed lipids in meibum samples from patients with dry eye disease (DED) in
order to better understand the underlying pathologic mechanisms. Methods: Meibum
samples were collected from postmenopausal women with DED (PW-DED; n = 5) and a
control group of postmenopausal women without DED (n = 4). Lipid profiles were
analyzed by direct infusion full-scan electrospray ionization mass spectrometry
(ESI-MS). An initial analysis of 145 representative peaks from four classes of
lipids in PW-DED samples revealed that additional manual corrections for peak
overlap and isotopes only slightly affected the statistical analysis. Therefore,
analysis of uncorrected data, which can be applied to a greater number of peaks,
was used to compare more than 500 lipid peaks common to PW-DED and control
samples. Statistical analysis of peak intensities identified several lipid
species that differed significantly between the two groups. Data from contact
lens wearers with DED (CL-DED; n = 5) were also analyzed. Results: Many species
of the two types of diesters (DE) and very long chain wax esters (WE) were
decreased by ~20% in PW-DED, whereas levels of triacylglycerols were increased by
an average of 39% +/- 3% in meibum from PW-DED compared to that in the control
group. Approximately the same reduction (20%) of similar DE and WE was observed
for CL-DED. Conclusions: Statistical analysis of peak intensities from direct
infusion ESI-MS results identified differentially expressed lipids in meibum from
dry eye patients. Further studies are warranted to support these findings.
PMID- 28426870
TI - A New Viscous Cysteamine Eye Drops Treatment for Ophthalmic Cystinosis: An Open
Label Randomized Comparative Phase III Pivotal Study.
AB - Purpose: The purpose of this study was to evaluate the efficacy of new viscous
cysteamine hydrochloride (CH) eye drops (vCH 0.55%) compared with standard CH
0.10% drops treatment. Methods: This was an open-label, phase III, randomized,
two-arm multicenter trial conducted at two centers in France. Cystinosis patients
>=2 years old were randomized 1:1 to receive eye drops, four times per day for 90
days in both eyes. We compared the superiority in reducing corneal cystine
crystal density as assessed by in vivo confocal microscopy (IVCM). We also
evaluated photophobia, corneal cystine crystal scores (CCCSs), and cystine
crystal depth measured by optical coherence tomography. Safety objectives were to
assess adverse events (AEs), local adverse drug reactions, and ocular safety
parameters. Results: We included 15 patients with vCH 0.55% and 16 patients with
CH 0.10% drops for 90 days. The mean absolute change in IVCM total score at day
90 in the vCH 0.55% drops group (-4.6 +/- 3.1) was significantly greater than and
superior to the mean absolute change in the CH 0.10% drops group (-0.46 +/- 3.38;
P < 0.0001). Photophobia, CCCS, and corneal cystine crystal depth were
significantly more improved in the vCH 0.55% drops group than in the CH 0.10%
group. The most frequent local adverse drug reactions in both groups were
stinging, burning, redness, and blurred vision. Conclusions: vCH 0.55% was
effective in reducing corneal cystine crystal density and superior to treatment
with CH 0.10% drops, which offer advantages over hospital pharmacy formulations
and is a more preferable and convenient treatment option.
PMID- 28426871
TI - Macular Pigment Density and Quantitative Fundus Autofluorescence in Young Healthy
Subjects.
AB - Purpose: To measure macular pigment (MP) and find possible correlation between
heterochromatic flicker photometry (HFP) and quantitative autofluorescence (qAF)
in young healthy subjects. Methods: We enrolled 80 eyes of 40 young healthy
subjects. Macular pigment optical density (MPOD) was automatically calculated
with a macular pigment screener (MPS; MPODHFP). We calculated qAF comparing gray
levels (GL) of qAF images with GL of internal reference of a confocal scanning
laser ophthalmoscopy. A raster of concentric rings was used to automatically
calculate foveal qAF (qAFF) values (0 degrees -1.2 degrees ); inner ring (1.3
degrees -4.3 degrees ; qAF3); middle ring (4.5 degrees -7 degrees ; qAF6); and
outer ring (7.2 degrees -9.7 degrees ; qAF8). The test-retest coefficient of
repeatability was calculated with Bland-Altman method. The between-eyes
coefficient of agreement and correlation between the two techniques were
calculated. Finally, an estimation of MPOD from qAF was performed (MPOD-AF), to
find possible direct correlations with MPODHFP obtained with the MPS II. Results:
Paired data sets of repeated measurements were not statistically different for
MPS II (P = 0.66); log qAFF (P = 0.95); log qAF3 (P = 0.48); log qAF6 (P = 0.4);
and log qAF8 (P = 0.56). Stepwise regression analysis showed negative correlation
between MPS II and log qAFF values (R2 = 0.35) with Spearman coefficient (rho) of
-0.60 (P < 0.01) and log qAF3 (R2 = 0.18; rho = -0.38.; P < 0.01). No correlation
was found between MPS II and log qAF6 (rho = 0.01, P = 0.93), neither with log
qAF8 (rho = -0.05, P = 0.66). Conclusions: In young healthy subjects, a negative
correlation between qAF values and MPODHFP was found in the central degrees.
However, qAF and HFP do not seem to be interchangeable: they represent two
opposite ways of estimating MP.
PMID- 28426872
TI - Importance and Difficulties of Pursuing rTMS Research in Acute Stroke.
AB - Although much research has been done on repetitive transcranial magnetic
stimulation (rTMS) in chronic stroke, only sparse research has been done in acute
stroke despite the particularly rich potential for neuroplasticity in this stage.
We attempted a preliminary clinical trial in one active, high-quality inpatient
rehabilitation facility (IRF) in the -United States. But after enrolling only 4
patients in the grant period, the study was stopped because of low enrollment.
The purpose of this paper is to offer a perspective describing the important
physiologic rationale for including rTMS in the early phase of stroke, the
reasons for our poor patient enrollment in our attempted study, and
recommendations to help future studies succeed. We conclude that, if scientists
and clinicians hope to enhance stroke outcomes, more attention must be directed
to leveraging conventional rehabilitation with neuromodulation in the acute phase
of stroke when the capacity for neuroplasticity is optimal. Difficulties with
patient enrollment must be addressed by reassessing traditional inclusion and
exclusion criteria. Factors that shorten patients' length of stay in the IRF must
also be reassessed at all policy-making levels to make ethical decisions that
promote higher functional outcomes while retaining cost consciousness.
PMID- 28426873
TI - High-fat diet induced leptin and Wnt expression: RNA-sequencing and pathway
analysis of mouse colonic tissue and tumors.
AB - Obesity, an immense epidemic affecting approximately half a billion adults, has
doubled in prevalence in the last several decades. Epidemiological data support
that obesity, due to intake of a high-fat, western diet, increases the risk of
colon cancer; however, the mechanisms underlying this risk remain unclear. Here,
utilizing next generation RNA sequencing, we aimed to determine the high-fat diet
(HFD) mediated expression profile in mouse colon and the azoxymethane/dextran
sulfate sodium model of colon cancer. Mice on HFD had significantly higher
colonic inflammation, tumor burden, and a number of differentially expressed
transcripts compared to mice on regular diet (RD). We identified 721 transcripts
differentially expressed in mouse HFD colon that were in a shared pattern with
colonic tumors (RD and HFD). Importantly, in mouse colon, HFD stimulated an
expression signature strikingly similar to human colon cancer, especially those
with inflammatory microsatellite instability. Furthermore, pathway analysis of
these transcripts demonstrated their association with active inflammation and
colon cancer signaling, with leptin and Wnt as the top two transcripts elevated
in mouse HFD colon shared with tumors. Moreover, in mouse colon, HFD-stimulated
tumorigenic Wnt pathway activation was further validated by upregulation of beta
catenin transcriptional targets. Finally, in human colon cancer, upregulation of
leptin pathway members was shown with a large network of dysregulated transcripts
being linked with worse overall survival.
PMID- 28426874
TI - The association between breast cancer and S100P methylation in peripheral blood
by multicenter case-control studies.
AB - Breast cancer (BC) is the leading cancer in women worldwide. Changes in DNA
methylation in peripheral blood could be associated with malignant diseases.
Making use of screening results by llumina 27K Methylation Assay, we validated
demethylation of five CpG sites of S100P gene in blood cell DNA of BC patients by
three independent retrospective studies with subjects from different centers
(Validation I: 235 familial BC case and 206 controls, odds ratio per -1%
methylation > 1.03, and P < 6.00 * 10-8 for all five CpG sites; Validation II:
189 sporadic BC case and 189 controls, odds ratio per -1% methylation > 1.03, P <
8.0 * 10-5 for four CpG sites; Validation III: 156 sporadic BC case and 151
controls, odds ratio per -1% methylation > 1.03, P < 6.0 * 10-4 for four CpG
sites). In addition, the blood-based S100P methylation pattern was similar among
BC patients with differential clinical characteristics regardless of stage,
receptor status and menopause status. The observed BC-associated decreased S100P
methylation in blood mainly originates from the leucocytes subpopulations but not
B cells. The methylation levels of most S100P CpG sites were inversely correlated
with the expression of S100P in leucocytes (P < 1.2 * 10-4) and in tissue (P <
1.1 * 10-4). This study reveals significant association between blood-based
decreased S100P methylation and BC, and provides another proof for the
application of altered DNA methylation signatures from blood cells as potential
markers for the detection of BC, especially for the early stage.
PMID- 28426875
TI - Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid
formation and resistance to EGFR pathway inhibition in estrogen receptor-negative
inflammatory breast cancer cells.
AB - Emerging evidence from epidemiological studies suggests a link between
environmental chemical exposure and progression of aggressive breast cancer
subtypes. Of all clinically distinct types of breast cancers, the most lethal
phenotypic variant is inflammatory breast cancer (IBC). Overexpression of
epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER)
negativity is common in IBC tumor cells, which instead of a solid mass present as
rapidly proliferating diffuse tumor cell clusters. Our previous studies have
demonstrated a role of an adaptive response of increased antioxidants in acquired
resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to
induce oxidative stress resulting in perturbations in signal transduction
pathways. It is therefore of interest to identify chemicals that can potentiate
EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a
subset of chemicals from the EPA ToxCast set for their effect on EGFR activation
and in multiple cancer phenotypic assays. We demonstrated that endocrine
disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1
trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding
increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of
antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and
tumor spheroid formation in vitro, reflecting IBC-specific pathological
characteristics. Furthermore, we identified that BPA was able to attenuate the
inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent
growth assay. These findings provide a potential mechanistic basis for
environmental chemicals such as BPA in potentiating a hyperproliferative and
death-resistant phenotype in cancer cells by activating mitogenic pathways to
which the tumor cells are addicted for survival.
PMID- 28426877
TI - Knockdown of hnRNPK leads to increased DNA damage after irradiation and reduces
survival of tumor cells.
AB - Radiotherapy is an important treatment option in the therapy of multiple tumor
entities among them head and neck squamous cell carcinoma (HNSCC). However, the
success of radiotherapy is limited by the development of radiation resistances.
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and
represents a potential target for radio sensitization of tumor cells. In this
study, we analyzed the impact of hnRNPK on the DNA damage response after gamma
irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA
damage levels in irradiated cells. Tumor cells bearing a p53 mutation showed
increased damage levels and delayed repair. Knockdown of hnRNPK applied
simultaneously with irradiation reduced colony-forming ability and survival of
tumor cells. Taken together, our data shows that hnRNPK is a relevant modifier of
DNA damage repair and tumor cell survival. We therefore recommend further studies
to evaluate the potential of hnRNPK as a drug target for improvement of
radiotherapy success.
PMID- 28426876
TI - Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related
multistage hepatocarcinogenesis: comparison with hepatitis virus-related
carcinogenesis.
AB - The aim of this study was to clarify the significance of DNA methylation
alterations during non-alcoholic steatohepatitis (NASH)-related
hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis
was performed on 264 liver tissue samples using the Illumina Infinium
HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed
significant DNA methylation alterations in 113 samples of non-cancerous liver
tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue
(NLT). Principal component analysis using the 3331 probes revealed distinct DNA
methylation profiles of NASH-N samples that were different from those of NLT
samples and 37 samples of non-cancerous liver tissue showing chronic hepatitis or
cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection (viral-N). Receiver operating characteristic curve analysis identified
194 probes that were able to discriminate NASH-N samples from viral-N samples
with area under the curve values of more than 0.95. Jonckheere-Terptsra trend
test revealed that DNA methylation alterations in NASH-N samples from patients
without hepatocellular carcinoma (HCC) were inherited by or strengthened in NASH
N samples from patients with HCC, and then inherited by or further strengthened
in 22 samples of NASH-related HCC (NASH-T) themselves. NASH- and NASH-related HCC
specific DNA methylation alterations, which were not evident in viral-N samples
and 37 samples of HCC associated with HBV or HCV infection, were observed in
tumor-related genes, such as WHSC1, and were frequently associated with mRNA
expression abnormalities. These data suggested that NASH-specific DNA methylation
alterations may participate in NASH-related multistage hepatocarcinogenesis.
PMID- 28426878
TI - Microbiota, NASH, HCC and the potential role of probiotics.
AB - Hepatocellular carcinoma (HCC) accounts for the majority of primary liver
cancers. Clearly identifiable risk factors are lacking in up to 30% of HCC
patients and most of these cases are attributed to non-alcoholic fatty liver
disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Beyond the known risk
factors for NAFLD, the intestinal microbiota, in particular dysbiosis (defined as
any change in the composition of the microbiota commonly found in healthy
conditions) is emerging as a new factor promoting the development of chronic
liver diseases and HCC. Intestinal microbes produce a large array of bioactive
molecules from mainly dietary compounds, establishing an intense microbiota-host
transgenomic metabolism with a major impact on physiological and pathological
conditions. A better knowledge of these 'new' pathways could help unravel the
pathogenesis of HCC in NAFLD to devise new prevention strategies. Currently
unsettled issues include the relative role of a 'negative microbiota' (in
addition to the other known risk factors for NASH) and the putative prevention of
NAFLD through modulation of the gut microbiota.
PMID- 28426879
TI - Acute exposure to DEHP metabolite, MEHP cause genotoxicity, mutagenesis and
carcinogenicity in mammalian Chinese hamster ovary cells.
AB - Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production
of polyvinyl chloride, can be converted to the more potent metabolite mono
ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association
with elevated induction of rat hepatic cancer and reproductive toxicity in
response to MEHP exposure. However, the mechanism of genotoxicity and
carcinogenicity induced by MEHP treatment remains unclear. As a means to
elucidate the mechanisms of action, lethality and mutagenicity in the adenine
phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by
MEHP were assessed. Dose-response relationships were determined in the parental
AA8 cell line, its nucleotide repair-deficient UV5 and base repair-deficient EM9
subclones, and also in AS52 cells harboring the bacterial guanine-hypoxanthine
phosphoribosyltransferase (gpt) gene and its derived AS52-XPD-knockdown and AS52
PARP-1-knockdown cells. Treatment of AS52 with MEHP led to intracellular
production of reactive oxygen species (ROS) and DNA strand breaks in a dose
dependent manner. Separately, mutations in the gpt gene of AS52 cells were
characterized and found to be dominated by G:C to A:T and A:T to G:C transitions.
Independent AS52-mutant cell (ASMC) clones were collected for the sequential in
vivo xenograft tumorigenic studies, 4 of total 20 clones had aggressive tumor
growth. Moreover, microarray analysis indicated miR-let-7a and miR-125b
downregulated in ASMC, which might raise oncogenic MYC and RAS level and activate
ErbB pathway. Comparative evaluation of the results indicates that the principal
mechanism of this mutagenic action is probably to be through generation of ROS,
causing base excision damage resulting in carcinogenicity.
PMID- 28426880
TI - Surgeon Volume in Parathyroid Surgery-Surgical Efficiency, Outcomes, and
Utilization.
PMID- 28426881
TI - New-generation CZT cameras: the future of infection imaging?
PMID- 28426882
TI - From conventional to molecular imaging: delineating mechanisms, diagnosis, and
outcomes.
PMID- 28426883
TI - Challenges in the Management of Fungal Keratitis.
PMID- 28426885
TI - Prognostic implications of left ventricular global longitudinal strain in heart
failure patients with narrow QRS complex treated with cardiac resynchronization
therapy: a subanalysis of the randomized EchoCRT trial.
AB - Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic
function and correlates inversely with the extent of LV myocardial scar and
fibrosis. The present subanalysis of the Echocardiography Guided CRT trial
investigated the prognostic value of LV GLS in patients with narrow QRS complex.
Methods and results: Left ventricular (LV) global longitudinal strain (GLS) was
measured on the apical 2-, 4- and 3-chamber views using speckle tracking
analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with
cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median
value of LV GLS in the overall population was 7.9%, interquartile range 6.2
10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF
group and 111 in the CRT-ON group reached the combined primary endpoint of all
cause mortality and heart failure hospitalization. Each 1% absolute unit decrease
in LV GLS was independently associated with 11% increase in the risk to reach the
primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04-1.17, P <
0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment
among other clinically relevant variables. When categorizing patients according
to quartiles of LV GLS, the primary endpoint occurred more frequently in patients
in the lowest quartile (<6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%,
P = 0.009) whereas, no differences were observed in patients with LV GLS >=6.2%
treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P = 0.62).
Conclusion: Low LV GLS is associated with poor outcome in heart failure patients
with QRS width <130 ms, independent of randomization to CRT or not. Importantly,
in the group of patients with the lowest LV GLS quartile, CRT may have a
detrimental effect on clinical outcomes.
PMID- 28426887
TI - Frontiers in heart failure: sodium, longitudinal strain, contractility sensor,
fatal arrhythmias, and stroke.
PMID- 28426886
TI - Risk of stroke in chronic heart failure patients with preserved ejection
fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I
Preserve trials.
AB - Aims: The incidence and predictors of stroke in patients with heart failure and
preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are
unknown. We described the incidence of stroke in HF-PEF patients with and without
AF and predictors of stroke in those without AF. Methods and results: We pooled
data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we
derived a model for stroke in patients without AF in this cohort and compared its
performance with a published model in heart failure patients with reduced
ejection fraction (HF-REF)-predictive variables: age, body mass index, New York
Heart Association class, history of stroke, and insulin-treated diabetes. The two
stroke models were compared and Kaplan-Meier curves for stroke estimated. The
risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did
not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF
(rates 1.80 and 1.00 per 100 patient-years, respectively). There was no
difference in performance of the stroke model derived in the HF-PEF cohort and
the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs.
0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model
performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in
patients in the upper third of risk approximated to that in patients with AF
(1.60 and 1.80 per 100 patient-years, respectively). Conclusions: A small number
of clinical variables identify a subset of patients with HF-PEF, but without AF,
at elevated risk of stroke.
PMID- 28426888
TI - Adolescent Depression: Differential Symptom Presentations in Deaf and Hard-of
Hearing Youth Using the Patient Health Questionnaire-9.
AB - The present study examined differences in symptom presentation in screening for
pediatric depression via evaluation of the Patient Health Questionnaire-9 (PHQ
9). In particular, we examined whether PHQ-9 items function differentially among
deaf and hard-of-hearing (DHH; n = 75) and hearing (n = 75) youth based on
participants recruited from crisis assessment services. Multiple indicators
multiple causes models were used to examine whether items of the PHQ-9 functioned
differently between groups as well as whether there were group differences in the
mean severity of depressive symptoms. Results indicate that DHH youth were more
likely to endorse psychosomatic items, and less likely to endorse an affective
item. These findings indicate that the PHQ-9 functions differently when used with
DHH youth. Implications of these findings are discussed, including both for
future work with the PHQ-9 and with regard to the conceptualization of depression
across hearing groups.
PMID- 28426889
TI - Concurrent and Longitudinal Predictors of Reading for Deaf and Hearing Children
in Primary School.
AB - Forty-one children with severe-profound prelingual hearing loss were assessed on
single word reading, reading comprehension, English vocabulary, phonological
awareness and speechreading at three time points, 1 year apart (T1-T3). Their
progress was compared with that of a group of hearing children of similar
nonverbal IQ, initially reading at the same level. Single word reading improved
at each assessment point for the deaf children but there was no growth in reading
comprehension from T2 to T3. There were no differences between children with
cochlear implants and those with hearing aids on either reading measure but
orally educated children had higher scores than children who signed in the
classroom. English vocabulary and speechreading were the most consistent
longitudinal predictors of reading for the deaf children. Phonological awareness
was the most consistent longitudinal predictor for the hearing group and also a
concurrent predictor of reading at T3 for both groups. There were many more
significant correlations among the various measures for the deaf children than
the hearing at both T1 and T3, suggesting that skills underpinning reading,
including phonological awareness and vocabulary, are more closely related for
deaf children. Implications of these findings for of deaf children's literacy are
explored.
PMID- 28426891
TI - Experiences of nurses with the care of patients with dementia in acute hospitals:
A secondary analysis.
AB - AIMS AND OBJECTIVES: To describe nurses' experiences in caring for people with
dementia in acute hospital settings. BACKGROUND: Recent research suggests that
nurses' experience in caring for people with dementia in acute hospitals is
characterised by frustration, overall job dissatisfaction and feelings of
powerlessness and guilt. Despite a growing body of knowledge concerning the care
of people with dementia in acute care settings, it remains unclear how nurses in
acute hospitals provide care for people with dementia and what general conditions
characterise the nursing care provided to these patients. DESIGN: A qualitative
secondary analysis was conducted. METHODS: Data were collected using audio
recorded focus group discussions with nurses in Germany and Austria. Overall, 12
focus group discussions, which were part of two larger research projects in
Germany and Austria, were expanded into a qualitative secondary analysis (a
content analysis). RESULTS: The findings show that nurses face great uncertainty
in caring for people with dementia in acute hospital settings and that each nurse
reacts in different ways to address this uncertainty. The results also underline
that, even for nurses who provide some form of person-centred care, the hospital
environment imposes several contextual constraints. CONCLUSIONS: Hospitals must
minimise constraints to give every nurse the chance to perform person-centred
care. Furthermore, it is important to sensitise nurses and give them sufficient
training and education to enable them to care for people with dementia. RELEVANCE
TO CLINICAL PRACTICE: The results may contribute to a better understanding of the
factors that support or constrain person-centred nursing care for people with
dementia in acute hospitals.
PMID- 28426893
TI - Diffuse normolipemic plane xanthoma on striae.
PMID- 28426892
TI - "I am still passionate despite the challenges": Nurses navigating the care for
refugees.
AB - AIMS AND OBJECTIVES: To report the challenges faced by the nursing workforce in
refugee health. BACKGROUND: Nurses are in the forefront of care provision for
refugees who are recognised as one of the most vulnerable population groups in
the world. The number of refugees in Australia is increasing, and more nurses are
needed as care providers. Research on the challenges faced by refugee health
nurses is sparse. DESIGN: Qualitative research methodology was used to study the
experience of refugee health nurses. Using a descriptive qualitative research
approach, a better understanding of the ongoing challenges of caring for refugees
is presented. METHOD: Semi-structured interview with a convenience sample of
registered nurses who worked in New South Wales refugee health services was
conducted and digitally recorded in 2013. Responses were transcribed verbatim and
analysed for themes. RESULTS: Six refugee health nurses who have been working in
New South Wales refugee health services between 1-8 years participated in this
study. A thematic analysis of the data led to three main themes: caring for
clients with challenging needs; challenges in the course of caring for refugees;
and passion in caring for refugees. Participants reported what it means to be
refugee health nurses, they explored their roles and emphasised the need to
understand refugee health issues. CONCLUSIONS: This study provides more insight
into the unique experiences nurses have when caring for refugees. More debriefing
opportunities and resources may reduce the challenges of caring. RELEVANCE TO
CLINICAL PRACTICE: The refugee health nurses' stories support the need for
further role refinement for nurses caring for refugees in the community, rural
areas and health clinics. This is essential in promoting their well-being and
that of the vulnerable population they are caring for.
PMID- 28426890
TI - Fine-mapping of lipid regions in global populations discovers ethnic-specific
signals and refines previously identified lipid loci.
AB - Genome-wide association studies have identified over 150 loci associated with
lipid traits, however, no large-scale studies exist for Hispanics and other
minority populations. Additionally, the genetic architecture of lipid-influencing
loci remains largely unknown. We performed one of the most racially/ethnically
diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date
using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African
Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians.
The majority of signals found in these groups generalize to European Americans.
While we uncovered signals unique to racial/ethnic populations, we also observed
systematically consistent lipid associations across these groups. In African
Americans, we identified three novel signals associated with HDL-C (LPL, APOA5,
LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this
population, we refined the location for 16 out of the 58 known MetaboChip lipid
loci. These results can guide tailored screening efforts, reveal population
specific responses to lipid-lowering medications, and aid in the development of
new targeted drug therapies.
PMID- 28426894
TI - Characteristics and Course of Enthesitis in a Juvenile Idiopathic Arthritis
Inception Cohort.
AB - OBJECTIVE: To describe the prevalence, associated characteristics, and course of
enthesitis in a juvenile idiopathic arthritis (JIA) inception cohort. METHODS:
Canadian children newly diagnosed with JIA between 2005 and 2010 were categorized
using International League of Associations for Rheumatology criteria at the 6
month visit and followed in the Research in Arthritis in Canadian Children
Emphasizing Outcomes (ReACCh-Out) cohort for up to 5 years. The presence of
entheseal tenderness on examination at 33 sites shown on a homunculus was
recorded at 0, 6, 12, 18, 24, 36, 48, and 60 months after enrollment. Enthesitis
was defined as entheseal tenderness at more than 1 site or on more than 1
occasion. Analyses consisted of descriptive statistics and linear mixed models
for longitudinal data. RESULTS: Of 1,406 patients, 219 (16%) had enthesitis and,
of those with enthesitis, 141 (64%) were classified as having enthesitis-related
arthritis (ERA). Children with enthesitis were more often older (10.7 versus 7.5
years), male (57% versus 31%), and with polyarthritis (57% versus 41%) and
sacroiliac involvement (30% versus 4%). Entheseal tenderness was most frequent at
the calcaneal plantar fascial insertion (39%), Achilles tendon insertion (31%),
and tibial tuberosity (30%). The mean number of tender entheseal sites decreased
in parallel with active joint counts. There was no difference in active joint
counts over time in children with or without enthesitis (P = 0.73). CONCLUSION:
Enthesitis was observed in 16% of patients with JIA, but only two thirds were
categorized as having ERA. Contrary to expectations, most children with
enthesitis had polyarticular involvement. The course of enthesitis paralleled the
course of active joint counts.
PMID- 28426896
TI - A note on marginalization of regression parameters from mixed models of binary
outcomes.
AB - This article discusses marginalization of the regression parameters in mixed
models for correlated binary outcomes. As is well known, the regression
parameters in such models have the "subject-specific" (SS) or conditional
interpretation, in contrast to the "population-averaged" (PA) or marginal
estimates that represent the unconditional covariate effects. We describe an
approach using numerical quadrature to obtain PA estimates from their SS
counterparts in models with multiple random effects. Standard errors for the PA
estimates are derived using the delta method. We illustrate our proposed method
using data from a smoking cessation study in which a binary outcome (smoking,
Y/N) was measured longitudinally. We compare our estimates to those obtained
using GEE and marginalized multilevel models, and present results from a
simulation study.
PMID- 28426897
TI - The effects of awareness and count duration on adult respiratory rate
measurements: An experimental study.
AB - AIMS AND OBJECTIVES: To investigate whether awareness of manual respiratory rate
monitoring affects respiratory rate in adults, and whether count duration
influences respiratory rate estimates. BACKGROUND: Nursing textbooks typically
suggest that the patient should ideally be unaware of respiratory rate
observations; however, there is little published evidence of the effect of
awareness on respiratory rate, and none specific to manual measurement. In
addition, recommendations about the length of the respiratory rate count vary
from text to text, and the relevant empirical evidence is scant, inconsistent and
subject to substantial methodological limitations. DESIGN: Experimental study
with awareness of respiration monitoring (aware, unaware; randomised between
subjects) and count duration (60 s, 30 s, 15 s; within-subjects) as the
independent variables. Respiratory rate (breaths/minute) was the dependent
variable. METHODS: Eighty-two adult volunteers were randomly assigned to aware
and unaware conditions. In the baseline block, no live monitoring occurred. In
the subsequent experimental block, the researcher informed aware participants
that their respiratory rate would be counted, and did so. Respirations were
captured throughout via video recording, and counted by blind raters viewing 60-,
30- and 15-s extracts. The data were collected in 2015. RESULTS: There was no
baseline difference between the groups. During the experimental block, the
respiratory rates of participants in the aware condition were an average of 2.13
breaths/minute lower compared to unaware participants. Reducing the count
duration from 1 min to 15 s caused respiratory rate to be underestimated by an
average of 2.19 breaths/minute (and 0.95 breaths/minute for 30-s counts). The
awareness effect did not depend on count duration. CONCLUSIONS: Awareness of
monitoring appears to reduce respiratory rate, and shorter monitoring durations
yield systematically lower respiratory rate estimates. RELEVANCE TO CLINICAL
PRACTICE: When interpreting and acting upon respiratory rate data, clinicians
should consider the potential influence of these factors, including cumulative
effects.
PMID- 28426895
TI - Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial
Lung Disease Associated With Systemic Sclerosis.
AB - OBJECTIVE: To determine the prognostic value of pulmonary function test (PFT)
trends at 1 and 2 years in interstitial lung disease (ILD) associated with
systemic sclerosis (SSc). METHODS: The prognostic significance of PFT trends at 1
year (n = 162) and 2 years (n = 140) was examined against 15-year survival in
patients with SSc-associated ILD. PFT trends, expressed as continuous change and
as categorical change in separate analyses, were examined against mortality in
univariate and multivariate models. SSc-associated ILD was defined at
presentation as either limited lung fibrosis or extensive lung fibrosis, using
the United Kingdom Raynaud's and Scleroderma Association severity staging system.
RESULTS: One-year PFT trends were predictive of mortality only in patients with
extensive lung fibrosis: categorical change in the forced vital capacity (FVC),
alone or in combination with categorical change in the diffusing capacity for
carbon monoxide (DLco), had greater prognostic significance than continuous
change in the FVC or trends in other PFT variables. Taking into account both
prognostic value and sensitivity to change, the optimal definition of progression
for trial purposes was an FVC and DLco composite end point, consisting of either
an FVC decline from baseline of >=10% or an FVC decline of 5-9% in association
with a DLco decline of >=15%. At 2 years, gas transfer trends had the greatest
prognostic significance, in the whole cohort and in those with limited lung
fibrosis. However, in patients with extensive lung fibrosis, the above-defined
FVC and DLco composite end point was the strongest prognostic determinant. Larger
changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient
were required to achieve prognostic significance. CONCLUSION: Based on linkages
to long-term outcomes, these findings provide support for use of routine
spirometry and gas transfer monitoring in patients with SSc-associated ILD, with
further evaluation of a composite FVC and DLco end point warranted for trial
purposes.
PMID- 28426898
TI - Improving myoblast differentiation on electrospun poly(epsilon-caprolactone)
scaffolds.
AB - Polymer scaffolds are used as an alternative to support tissue regeneration when
it does not occur on its own. Cell response on polymer scaffolds is determined by
factors such as polymer composition, topology, and the presence of other
molecules. We evaluated the cellular response of murine skeletal muscle myoblasts
on aligned or unaligned fibers obtained by electrospinning poly(epsilon
caprolactone) (PCL), and blends with poly(lactic-co-glycolic acid) (PLGA) or
decorin, a proteoglycan known to regulate myogenesis. The results showed that
aligned PCL fibers with higher content of PLGA promote cell growth and improve
the quality of differentiation with PLGA scaffolds having the highest confluence
at over 68% of coverage per field of view for myoblasts and more than 7% of
coverage for myotubes. At the same time, the addition of decorin greatly improves
the quantity and quality of differentiated cells in terms of cell fusion, myotube
length and thickness, being 71, 10, and 51% greater than without the protein,
respectively. Interestingly, our results suggest that at certain concentrations,
the effect of decorin on myoblast differentiation exceeds the topological effect
of fiber alignment. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
105A: 2241-2251, 2017.
PMID- 28426899
TI - Ultrasonographic features of intravascular fasciitis: case report and review of
the literature.
PMID- 28426900
TI - Videodermoscopy supports the diagnosis of eyelash trichotillomania.
PMID- 28426901
TI - A case of toxic epidermal necrolysis and vanishing bile duct syndrome, requiring
liver transplantation.
PMID- 28426902
TI - Hepatic steatosis after pediatric liver transplant.
AB - Hepatic steatosis develops after liver transplantation (LT) in 30% of adults, and
nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease
in nontransplanted children. However, posttransplant steatosis has been minimally
studied in pediatric LT recipients. We explored the prevalence, persistence, and
association with chronic liver damage of hepatic steatosis in these children. In
this single-center study of pediatric patients transplanted 1988-2015 (n = 318),
31% of those with any posttransplant biopsy (n = 271) had >= 1 biopsy with
steatosis. Median time from transplant to first biopsy with steatosis was 0.8
months (interquartile range [IQR], 0.3-6.5 months) and to last biopsy with
steatosis was 5.5 months (IQR, 1.0-24.5 months); 85% of patients with steatosis
also had for-cause biopsies without steatosis. All available for-cause biopsies
were re-evaluated (n = 104). Of 9 biopsies that could be interpreted as
nonalcoholic steatohepatitis (NASH)/borderline NASH, with steatosis plus
inflammation or ballooning, 8 also had features of cholestasis or rejection.
Among 70 patients with surveillance biopsies 3.6-20.0 years after transplant,
only 1 overweight adolescent had a biopsy with NAFLD (grade 1 steatosis, mild
inflammation, no ballooning or fibrosis)-despite a 30% prevalence of
overweight/obesity in the cohort and 27% with steatosis on previous for-cause
biopsy. Steatosis on preceding for-cause biopsy was not associated with portal (P
= 0.49) or perivenular fibrosis (P = 0.85) on surveillance biopsy. Hepatic
steatosis commonly develops early after transplant in children and adolescents,
but it rarely persists. Biopsies that did have steatosis with NASH
characteristics were all for-cause, mostly in patients with NAFLD risk factors
and/or confounding causes of liver damage. Prospective studies that follow
children into adulthood will be needed to evaluate if and when hepatic steatosis
presents a longterm risk for pediatric LT recipients. Liver Transplantation 23
957-967 2017 AASLD.
PMID- 28426903
TI - The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated
Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical
Trial.
AB - OBJECTIVE: To assess the therapeutic efficacy of local injections of botulinum
toxin type A (Btx-A) in improving blood flow to the hands of patients with
Raynaud's phenomenon (RP) secondary to scleroderma. METHODS: In this randomized,
double-blind, placebo-controlled clinical trial, patients with scleroderma
associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly
selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1
and 4 months postinjection included laser Doppler imaging of hands, patient
reported outcomes, and physical examination. We compared outcomes using paired t
tests and population-average generalized models with generalized estimating
equations. RESULTS: Of 40 patients enrolled, 25 had limited scleroderma and 15
had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater
reduction in average blood flow in Btx-A-treated hands compared to placebo
treated hands. The model estimated that this difference was statistically
significant (average difference -30.08 flux units [95% confidence interval
56.19, -3.98], P for interaction = 0.024). This difference was mainly influenced
by patients with longstanding RP and diffuse scleroderma. Change in blood flow at
4-month follow-up was not significantly different between groups. Clinical
measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog
scale, and Raynaud's Condition Score) improved slightly for Btx-A-treated hands.
CONCLUSION: Our laboratory-based laser Doppler imaging flow data do not support
using Btx-A to treat RP in all scleroderma patients. The secondary clinical
outcomes suggest some positive effect, but its clinical meaningfulness is
questionable. The role of Btx-A in treating RP should be further studied with
more homogeneous patient populations and in unique clinical situations such as
acute digital ischemia.
PMID- 28426904
TI - In vitro study of the proliferation and growth of human fetal osteoblasts on Mg
and Si co-substituted tricalcium phosphate ceramics.
AB - The objective of this work was to study the feasibility of the solid state
sintering, a conventional ceramic processing method, to obtain Mg and Si co
substituted tricalcium phosphate bioceramics and composites containing diopside.
A series of new Ca3 (PO4 )2 based ceramics has been prepared from attrition
milled mixtures of synthetic Ca3 (PO4 )2 and CaMg(SiO3 )2 powders, isostatically
pressed and sintered at 1250-1300 degrees C. Materials containing 0, 1, and 5 wt
% of CaMg(SiO3 )2 were constituted by beta + alpha - Ca3 (PO4 )2 solid solutions
while the material containing 60 wt % of CaMg(SiO3 )2 was a constituted by beta-
Ca3 (PO4 )2 and CaMg(SiO3 )2 . The biological responses of the developed ceramics
were studied in vitro using human fetal osteoblast cultures. Culture times ranged
from 1 to 21 days. The new family of materials promotes the adhesion and
proliferation of human osteoblasts cultured onto their surface forming a
monolayer and showing a normal morphology. The results of the MTT and Alamar Blue
assays showed that the soluble components extracted from the Mg/Si- co
substituted Ca3 (PO4 )2 and the Ca3 (PO4 )2 -CaMg(SiO3 )2 composite were
noncytotoxic. The specimens with diopside exhibited a better in vitro behavior
which is attributed to the release of Si and Mg ions to the culture medium,
enhancing the activity of cells. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
Res Part A: 105A: 2266-2275, 2017.
PMID- 28426905
TI - Acantholytic dyskeratotic acanthoma: a possible skin adverse event of vemurafenib
treatment.
PMID- 28426906
TI - Measuring the impact of dermatological conditions on family and caregivers: a
review of dermatology-specific instruments.
AB - The patient is the centre of a web of relationships, and the impact of his/her
disease on family members and caregivers must be taken into account. The aim of
this study was to identify the specific instruments that measure the impact of a
dermatological disease on the quality of life (QoL) of family members, by
performing a systematic search of the literature. Fifteen papers were identified,
describing the creation and validation of nine instruments. Four of them
concerned atopic dermatitis (Dermatitis Family Index, DFI; Parents' Index QoL
Atopic Dermatitis, PiQoL-AD; QoL in primary caregivers of children with atopic
dermatitis, QPCAD; Childhood Atopic Dermatitis Impact Scale, CADIS), two measured
the impact of psoriasis in family members (Psoriasis Family Index, PFI;
FamilyPso), one the impact of epidermolysis bullosa (Epidermolysis Bullosa Burden
of Disease, EB-BoD), one of ichthyosis (Family Burden Ichthyosis, FBI), and one
was generic for dermatological conditions (Family Dermatology Life Quality Index,
FDLQI). The European Academy of Dermatology and Venereology quality of life
taskforce recommends that the impact of a skin disease on family and caregivers
should be measured as part of any thorough evaluation of the burden of a disease.
Guidelines are given to choose the most appropriate instruments.
PMID- 28426907
TI - Frontal fibrosing alopecia: clinical and prognostic classification.
AB - BACKGROUND: Frontal fibrosing alopecia (FFA) is a chronic scarring alopecia with
an unpredictable evolution. There are no current classifications of this disease
that may predict its prognosis. OBJECTIVE: To analyse the differences in clinical
presentation and evolution of FFA patients and to create a clinical and
prognostic classification. METHODS: We conducted a retrospective analytical study
of FFA patients. Clinical characteristics of frontal hairline recession were used
as the sorting variable between patterns of presentation. A cohort of 106
patients homogenously treated with oral dutasteride and topical corticosteroid
was followed 12 months. RESULTS: In all, 242 female patients with a mean age of
61.4 years were included. Patients were classified into three clinical patterns
[118 (48.8%) patients as pattern I (linear), 109 patients (45%) as pattern II
(diffuse) and 15 patients (6.2%) as pattern III (double line)]. Stabilization was
achieved in 37.3% of the 106 patients treated with oral dutasteride and topical
corticosteroid. Pattern III patients had less hairline recession and eyebrow
involvement at the diagnosis and after treatment. LIMITATIONS: Retrospective
design. CONCLUSIONS: Frontal fibrosing alopecia patients can be classified into
three different clinical patterns with different prognosis. Pattern III patients
have the best prognosis, while pattern II patients have the worst prognosis.
PMID- 28426908
TI - Clinically useful brain imaging for neuropsychiatry: How can we get there?
AB - Despite decades of research, visions of transforming neuropsychiatry through the
development of brain imaging-based "growth charts" or "lab tests" have remained
out of reach. In recent years, there is renewed enthusiasm about the prospect of
achieving clinically useful tools capable of aiding the diagnosis and management
of neuropsychiatric disorders. The present work explores the basis for this
enthusiasm. We assert that there is no single advance that currently has the
potential to drive the field of clinical brain imaging forward. Instead, there
has been a constellation of advances that, if combined, could lead to the
identification of objective brain imaging-based markers of illness. In
particular, we focus on advances that are helping to (1) elucidate the research
agenda for biological psychiatry (e.g., neuroscience focus, precision medicine),
(2) shift research models for clinical brain imaging (e.g., big data exploration,
standardization), (3) break down research silos (e.g., open science, calls for
reproducibility and transparency), and (4) improve imaging technologies and
methods. Although an arduous road remains ahead, these advances are repositioning
the brain imaging community for long-term success.
PMID- 28426909
TI - Nursing and pharmacy students' use of emotionally intelligent behaviours to
manage challenging interpersonal situations with staff during clinical placement:
A qualitative study.
AB - AIMS AND OBJECTIVES: To identify challenging interpersonal interactions
experienced by nursing and pharmacy students during clinical placement, and
strategies used to manage those situations. BACKGROUND: Healthcare students and
staff experience elevated stress when exposed to dynamic clinical environments,
complex care and challenging professional relationships. Emotionally intelligent
behaviours are associated with appropriate recognition and management of emotions
evoked by stressful experiences and development of effective relationships.
Nursing and pharmacy students' use of emotionally intelligent behaviours to
manage challenging interpersonal situations is not well known. DESIGN: A
qualitative design, using semi-structured interviews to explore experiences of
challenging interpersonal situations during clinical placement (Phase two of a
larger mixed-methods study). Final-year Australian university nursing and
pharmacy students (n = 20) were purposefully recruited using a range of Emotional
Intelligence scores (derived in Phase one), measured using the GENOS Emotional
intelligence Inventory (concise version). RESULTS: Challenging interpersonal
situations involving student-staff and intrastaff conflict, discourteous
behaviour and criticism occurred during clinical placement. Students used
personal and relational strategies, incorporating emotionally intelligent
behaviours, to manage these encounters. Strategies included reflecting and
reframing, being calm, controlling discomfort and expressing emotions
appropriately. CONCLUSIONS: Emotionally intelligent behaviours are effective to
manage stressful interpersonal interactions. Methods for strengthening these
behaviours should be integrated into education of nursing and pharmacy students
and qualified professionals. Education within the clinical/workplace environment
can incorporate key interpersonal skills of collaboration, social interaction and
reflection, while also attending to sociocultural contexts of the healthcare
setting. RELEVANCE TO CLINICAL PRACTICE: Students and staff are frequently
exposed to stressful clinical environments and challenging interpersonal
encounters within healthcare settings. Use of emotionally intelligent behaviours
to recognise and effectively manage these encounters may contribute to greater
stress tolerance and enhanced professional relationships. Nursing and pharmacy
students, and their qualified counterparts, need to be educated to strengthen
their emotional intelligence skills.
PMID- 28426910
TI - Family and Other Unpaid Caregivers and Older Adults with and without Dementia and
Disability.
AB - OBJECTIVES: To estimate the number of caregivers providing assistance to
community-dwelling older persons with and without dementia and with or without
substantial disability; to describe the characteristics of caregivers and care
recipients in these groups; to characterize the health-related tasks that
caregivers provide; and to estimate associations between the numbers of tasks and
caregiver burden. DESIGN: Nationally representative surveys of caregivers and
older adults in the United States. SETTING: 2011 National Health and Aging Trends
Study and National Study of Caregiving. PARTICIPANTS: Community-dwelling older
adults and their family caregivers, who were selected on the basis of having
assisted with mobility, self-care, household activities, transportation, or
medical tasks. MEASUREMENTS: Caregiver burden (emotional, physical, financial
difficulties) and restrictions on social participation. RESULTS: Although much
larger proportions of older adults with dementia and disability (98.4%, n = 1.0
million) and dementia but not disability (95.5%, n = 1.3 million) received
caregiving assistance, the largest absolute number of individuals receiving
assistance were older adults without dementia or disability (4.0 million). Within
each caregiver group, caregivers provided assistance with at least one task
across domains of activity of daily living and instrumental activity of daily
living-related assistance (>98%), health systems logistics (>70%), and health
management (>50%). There was a significant linear association between number of
tasks provided and risk of burden in virtually all caregiver groups and domains
of assistance. CONCLUSION: Caregivers of care recipients without dementia or
disability accounted for the largest absolute number of helpers. These
caregivers, similar to caregivers of care recipients with dementia or disability,
delivered a broad spectrum of health-related tasks and experienced caregiver
burden and restrictions on social participation. Findings support the need for
interventions that address the needs of caregivers who have not typically been
defined as high risk.
PMID- 28426912
TI - Association Between Inflammatory Back Pain Characteristics and Magnetic Resonance
Imaging Findings in the Spine and Sacroiliac Joints.
AB - OBJECTIVE: To investigate the association between magnetic resonance imaging
(MRI) findings at the sacroiliac (SI) joints and vertebral endplates and pain
characteristics assumed to be indicative of axial inflammation. METHODS: Patients
ages 18-40 years with persistent low back pain referred to an outpatient spine
clinic participated, including an unknown proportion of axial spondyloarthritis
patients. Data included MRI of the spine and SI joints and self-reported
responses to questions covering the Calin, Berlin, Assessment of
Spondyloarthritis International Society, and Bailly inflammatory back pain (IBP)
definitions. RESULTS: In the 1,020 included patients, 53% were women, and the
median age was 33 years. Positive associations were found between the SI joint
MRI findings and pain characteristics, odds ratios ranging from 1.4 to 2.7. SI
joint bone marrow edema (BME) was associated with morning stiffness >60 minutes,
and SI joint erosions with the Calin, Berlin, and Bailly IBP definitions,
alternating buttock pain, and good response to nonsteroidal antiinflammatory
drugs. SI joint fatty marrow deposition (FMD) was associated with insidious
onset, and SI joint sclerosis with pain at night. In addition, the spinal MRI
changes were associated with IBP, odds ratios ranging from 1.4 to 2.0; vertebral
endplate BME was associated with morning stiffness, and vertebral endplate FMD
with the Calin and Bailly IBP definitions, improvement with exercise, morning
stiffness >30 minutes, and pain worst in the morning. CONCLUSION: The identified
associations between inflammatory MRI findings and pain characteristics indicate
that axial inflammation to some degree induces a specific pain pattern. Thus, the
results add to knowledge of axial inflammatory processes. However, all identified
associations were weak, which compromises the use of IBP as a marker of axial
inflammation.
PMID- 28426911
TI - Brief Report: Blockade of TANK-Binding Kinase 1/IKKE Inhibits Mutant Stimulator
of Interferon Genes (STING)-Mediated Inflammatory Responses in Human Peripheral
Blood Mononuclear Cells.
AB - OBJECTIVE: Gain-of-function mutations in TMEM173, encoding the stimulator of
interferon (IFN) genes (STING) protein, underlie a novel type I interferonopathy
that is minimally responsive to conventional immunosuppressive therapies and
associated with high frequency of childhood morbidity and mortality. STING gain
of-function causes constitutive oversecretion of IFN. This study was undertaken
to determine the effects of a TANK-binding kinase 1 (TBK-1)/IKKE inhibitor
(BX795) on secretion and signaling of IFN in primary peripheral blood mononuclear
cells (PBMCs) from patients with mutations in STING. METHODS: PBMCs from 4
patients with STING-associated disease were treated with BX795. The effect of
BX795 on IFN pathways was assessed by Western blotting and an IFNbeta reporter
assay, as well as by quantification of IFNalpha in cell lysates, staining for
STAT-1 phosphorylation, and measurement of IFN-stimulated gene (ISG) messenger
RNA (mRNA) expression. RESULTS: Treatment of PBMCs with BX795 inhibited the
phosphorylation of IFN regulatory factor 3 and IFNbeta promoter activity induced
in HEK 293T cells by cyclic GMP-AMP or by genetic activation of STING. In vitro
exposure to BX795 inhibited IFNalpha production in PBMCs of patients with STING
associated disease without affecting cell survival. In addition, BX795 decreased
STAT-1 phosphorylation and ISG mRNA expression independent of IFNalpha blockade.
CONCLUSION: These findings demonstrate the effect of BX795 on reducing type I IFN
production and IFN signaling in cells from patients with gain-of-function
mutations in STING. A combined inhibition of TBK-1 and IKKE therefore holds
potential for the treatment of patients carrying STING mutations, and may also be
relevant in other type I interferonopathies.
PMID- 28426913
TI - Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid
Arthritis.
AB - OBJECTIVE: To examine associations of body mass index (BMI) and weight loss with
cause-specific mortality in rheumatoid arthritis (RA). METHODS: A cohort of US
veterans with RA was followed until death or through 2013. BMI was categorized as
underweight, normal, overweight, and obese. Weight loss was calculated as the 1)
annualized rate of change over the preceding 13 months, and 2) cumulative
percent. Vital status and cause of death were obtained from the National Death
Index. Multivariable competing-risks regression models were utilized to assess
the time-varying associations of BMI and weight loss with cause-specific
mortality. RESULTS: Among 1,600 participants and 5,789 patient-years of followup,
303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The
highest weight-loss rate and weight-loss percent were associated with a higher
risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27
[95% confidence interval (95% CI) 1.61-3.19]; percent: sHR 2.31 [95% CI 1.06
5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11-5.01]; percent: sHR 1.90
[95% CI 1.00-3.62]). Overweight BMI was protective of cardiovascular mortality
(sHR 0.59 [95% CI 0.38-0.91]), while underweight BMI was associated with a near 3
fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28-6.67]).
Incorporation of time-varying BMI and weight loss in the same models did not
substantially alter individual associations for cardiovascular and cancer
mortality, but an association between weight-loss percentage and respiratory
mortality was attenuated after BMI adjustment. CONCLUSION: Both BMI and weight
loss are predictors of cause-specific mortality in RA. Weight loss is a strong
predictor of cardiovascular and cancer mortality, while underweight BMI is a
stronger predictor of respiratory mortality.
PMID- 28426914
TI - The recommended dose of idarucizumab may not always be sufficient for sustained
reversal of dabigatran.
AB - : Essentials Reversal of anticoagulant effects of dabigatran may occur despite
application of idarucizumab. Monitoring of dabigatran level after antidote
application is crucial to detect rebound. Repeated doses of idarucizumab may be
necessary in cases of massive dabigatran accumulation. Combination of antidote
application and renal replacement therapy may offer additional benefit. SUMMARY:
Idarucizumab is a monoclonal antibody fragment designed for reversing the
anticoagulant effects of dabigatran. Administration is recommended as two
intravenous boluses of 2.5 g within 15 min of each other or as a single 5 g
bolus. However, in certain situations a second dose of the drug could be
necessary. We report the case of a 77-year-old man, treated with dabigatran for
paroxysmal atrial fibrillation. He presented at our department with acute renal
failure, concomitant massive dabigatran accumulation and subsequent acute
gastrointestinal bleeding. Fifty minutes after the administration of
idarucizumab, the dabigatran plasma concentration decreased from a peak of 1630
ng ml-1 to a level below the detection limit of 30 ng ml-1 and bleeding stopped.
Eight hours after administration, the dabigatran plasma level started to increase
up to 1560 ng ml-1 (96% of the maximum value obtained), accompanied by a further
drop in hemoglobin. Concomitant hemodialysis and hemofiltration led to a
continuous decrease in dabigatran plasma levels. However, sepsis and multiorgan
failure ensued, which led to death. With this case report we raise the question
of whether massive dabigatran accumulation requires repeated doses of
idarucizumab, or alternatively, if the combination of antidote with
hemodialysis/renal replacement therapy is advisable in order to remove
circulating levels of dabigatran.
PMID- 28426915
TI - Improvements in Colorectal Cancer Incidence Not Experienced by Nonmetropolitan
Women: A Population-Based Study From Utah.
AB - PURPOSE: Little is known about disparities in colorectal cancer (CRC) incidence
and mortality by community-level factors such as metropolitan status. METHODS:
This analysis utilized data from the Surveillance, Epidemiology, and End Results
(SEER) program from Utah. We included patients diagnosed with CRC from 1991 to
2010. To determine whether associations existed between
metropolitan/nonmetropolitan county of residence and CRC incidence, Poisson
regression models were used. CRC mortality was assessed using multivariable Cox
regression models. FINDINGS: CRC incidence rates did not differ between
metropolitan and nonmetropolitan counties by gender (males: 46.2 per 100,000 vs
45.1 per 100,000, P = .87; females: 34.4 per 100,000 vs 36.1 per 100,000, P =
.70). However, CRC incidence between the years of 2006 and 2010 in
nonmetropolitan counties was significantly higher in females (metropolitan: 30.4
vs nonmetropolitan: 37.0 per 100,000, P = .002). As compared to metropolitan
counties, the incidence of unstaged CRC in nonmetropolitan counties was
significantly higher in both males (1.7 vs 2.8 per 100,000, P = .003) and females
(1.4 vs 1.6 per 100,000, P = .002). Among patients who were diagnosed between
2006 and 2010, metropolitan counties were found to have significantly increased
survival among males and females, but nonmetropolitan counties showed increased
survival only for males. CONCLUSIONS: While we observed a decreasing incidence of
CRC among men and women in Utah, this effect was not seen in women in
nonmetropolitan areas nor among those with unstaged disease. Further studies
should evaluate factors that may account for these differences. This analysis can
inform interventions with a focus on women in nonmetropolitan areas.
PMID- 28426916
TI - Preconcentration and determination of 2-mercaptobenzimidazole by dispersive
liquid-liquid microextraction and experimental design.
AB - A method was developed to determine 2-mercaptobenzimidazole in water and urine
samples using dispersive liquid-liquid microextraction technique coupled with
ultraviolet-visible spectrophotometry. It was essential to peruse the effect of
all parameters that can likely influence the performance of extraction. The
influence of parameters, such as dispersive and extraction solvent volume and
sample volume, on dispersive liquid-liquid microextraction was studied. The
optimization was carried out by the central composite design method. The central
composite design optimization method resulted in 1.10 mL dispersive solvent,
138.46 MUL extraction solvent, and 4.46 mL sample volume. Under the optimal
terms, the calibration curve was linear over the range of 0.003-0.18 and 0.007
0.18 MUg/mL in water and urine samples, respectively. The limit of detection and
quantification of the proposed approach for 2-mercaptobenzimidazole were 0.013
and 0.044 MUg/mL in water samples and 0.016 and 0.052 MUg/mL in urine samples,
respectively. The method was successfully applied to determination of 2
mercaptobenzimidazole in urine and water samples.
PMID- 28426917
TI - Internet Cognitive-Behavioral Therapy for Depression in Older Adults With Knee
Osteoarthritis: A Randomized Controlled Trial.
AB - OBJECTIVE: To determine the efficacy of an internet-based cognitive-behavioral
therapy (iCBT) program for depression in older adults with osteoarthritis (OA) of
the knee and comorbid major depressive disorder (MDD). METHODS: We conducted a
randomized controlled trial in 69 adults (ages >=50 years) meeting criteria for
MDD and OA of the knee with 1-week postintervention (week 11) and 3-month
followup (week 24) end points. Patients were allocated to either a 10-week iCBT
program for depression added to treatment as usual (TAU) or to a TAU control
group. Primary outcomes were depression symptoms (9-Item Patient Health
Questionnaire [PHQ-9]) and psychological distress (Kessler-10 [K-10]). Secondary
outcomes included arthritis self-efficacy (Arthritis Self-Efficacy Scale [ASES]),
OA pain, stiffness, physical function (Western Ontario and McMaster Universities
Osteoarthritis Index [WOMAC]), and physical and mental health (Short Form 12-Item
health survey physical component and mental component summaries). Depression
status was assessed by blinded diagnostic interview (the Mini-International
Neuropsychiatric Interview) at intake and followup. RESULTS: Intent-to-treat
analyses indicated between-group superiority of iCBT over TAU on the primary
outcomes (PHQ-9: Hedges g = 1.01, 95% confidence interval [95% CI] 0.47, 1.54; K
10: Hedges g = 0.75, 95% CI 0.23, 1.28), at postintervention and 3-month followup
(PHQ-9: Hedges g = 0.90, 95% CI 0.36, 1.44; K-10: Hedges g = 0.94, 95% CI 0.41,
1.48), and on secondary OA-specific measures (ASES: Hedges g = -0.81, 95% CI
0.29, -1.33; WOMAC: Hedges g = 0.56-0.65, 95% CI 0.04, 1.18) at the 3-month
followup. The majority of iCBT participants (84%) no longer met diagnostic
criteria at 3-month followup. CONCLUSION: Results support the efficacy of an iCBT
program (requiring no face-to-face contact) for depression in individuals with
comorbid depression and OA of the knee. Importantly, the benefits of the program
extended beyond reduced depressive symptoms and distress to include increased
self-efficacy and improved pain, stiffness, and physical function at followup.
PMID- 28426918
TI - Advanced cancer caregiving as a risk for major depressive episodes and
generalized anxiety disorder.
AB - OBJECTIVE: Caregivers of advanced cancer patients provide extensive care
associated with high levels of caregiver distress. The degree to which cancer
caregiving increases caregivers' risk for a psychiatric disorder is unknown. The
current study examines whether advanced cancer caregiving poses distinct risks
for initial and recurrent major depressive episodes (MDEs) and generalized
anxiety disorder (GAD) relative to the general population. METHODS: Caregivers of
advanced cancer patients (N = 540) from Coping with Cancer were compared to
general population controls (N = 9282) from the National Comorbidity Survey
Replication. The general population comparison sample was propensity-weighted to
be demographically similar to the caregiver sample. RESULTS: Caregivers of
advanced cancer patients were more likely than individuals in the general
population to have an initial MDE (OR = 7.7; 95% CI, 3.5-17.0; P < .001), but no
more likely than the general population to have a recurrent MDE (OR = 1.1; 95%
CI, 0.6-2.1; P = .662). Caregivers were also more likely than the general
population to have GAD (OR = 3.0; 95% CI, 1.9-4.8; P < .001) and comorbid MDE and
GAD (OR = 2.5; 95% CI, 1.1-5.9; P = .038). CONCLUSIONS: The increased risk of
meeting diagnostic criteria for current MDE and GAD and comorbid MDE and GAD
associated with advanced cancer caregiving highlights the degree of emotional
burden among cancer caregivers. Clinical services that assess, prevent, and treat
depression and anxiety in cancer caregivers are needed to reduce the burden of
caregiving and improve the mental health of this growing population.
PMID- 28426919
TI - Unknown Intracardiac Electrogram.
AB - Watch a video presentation of this article. For additional educational resources,
please visit Medtronic Academy .
PMID- 28426920
TI - Dabigatran enhances platelet reactivity and platelet thrombin receptor expression
in patients with atrial fibrillation: comment.
PMID- 28426921
TI - The Marriage and Family Therapy Practice Research Network (MFT-PRN): Creating a
More Perfect Union Between Practice and Research.
AB - This article describes the Marriage and Family Therapy Practice Research Network
(MFT-PRN). The MFT-PRN is designed to build a professional community based on
practice-informed research and research-informed practice, increase the diversity
of participants in MFT research, and unify researchers and clinicians. Clinics
choose measures from a list that best represent their clinic needs. Clients'
outcomes are assessed regularly, and therapists receive immediate graphical
feedback on how clients are progressing or digressing. Data are pooled to create
a large and diverse database, while improving client outcomes. We will discuss
advantages of the MFT-PRN for researchers, therapists, clients, and agencies, and
provide one model that we hope will inform other collaborative clinical-research
models in the field of marriage and family therapy. Video Abstract is found in
the online version of the article.
PMID- 28426922
TI - Feasibility and acceptability of "healthy directions" a lifestyle intervention
for adults with lung cancer.
AB - OBJECTIVE: The aims of this feasibility study of an adapted lifestyle
intervention for adults with lung cancer were to (1) determine rates of
enrollment, attrition, and completion of 5 nurse-patient contacts; (2) examine
demographic characteristics of those more likely to enroll into the program; (3)
determine acceptability of the intervention; and (4) identify patient preferences
for the format of supplemental educational intervention materials. METHODS: This
study used a single-arm, pretest and posttest design. Feasibility was defined as
>=20% enrollment and a completion rate of 70% for 5 nurse-patient contact
sessions. Acceptability was defined as 80% of patients recommending the program
to others. Data was collected through electronic data bases and phone interviews.
Descriptive statistics, Fisher's exact test and Wilcoxon rank sum test were used
for analyses. RESULTS: Of 147 eligible patients, 42 (28.6%) enrolled and of
these, 32 (76.2%) started the intervention and 27 (N = 27/32; 84.4%; 95% CI,
67.2%-94.7%) completed the intervention. Patients who were younger were more
likely to enroll in the study (P = .04) whereas there were no significant
differences by gender (P = .35). Twenty-three of the 24 (95.8%) participants'
contacted posttest recommended the intervention for others. Nearly equal numbers
of participants chose the website (n = 16, 50%) vs print (n = 14, 44%).
CONCLUSION: The intervention was feasible and acceptable in patients with lung
cancer. Recruitment rates were higher and completion rates were similar as
compared to previous home-based lifestyle interventions for patients with other
types of cancer. Strategies to enhance recruitment of older adults are important
for future research.
PMID- 28426923
TI - Potassium-Promoted Molybdenum Carbide as a Highly Active and Selective Catalyst
for CO2 Conversion to CO.
AB - The high concentration of CO2 bound in seawater represents a significant
opportunity to extract and use this CO2 as a C1 feedstock for synthetic fuels.
Using an existing process, CO2 and H2 can be concurrently extracted from seawater
and then catalytically reacted to produce synthetic fuel. Hydrogenating CO2
directly into liquid hydrocarbons is exceptionally difficult, but by first
identifying a catalyst for selective CO production through the reverse water-gas
shift (RWGS) reaction, CO can then be hydrogenated to fuel through Fischer
Tropsch (FT) synthesis. Results of this study demonstrate that potassium-promoted
molybdenum carbide supported on gamma-Al2 O3 (K-Mo2 C/gamma-Al2 O3 ) is a low
cost, stable, and highly selective catalyst for RWGS over a wide range of
conversions. These findings are supported by X-ray diffraction, scanning electron
microscopy with energy-dispersive X-ray spectroscopy, X-ray photoelectron
spectroscopy, and density functional theory calculations.
PMID- 28426924
TI - High-dose pulsed corticosteroid therapy combined with methotrexate for severe
alopecia areata of childhood.
PMID- 28426925
TI - Understanding the Role of Antibodies as Markers of Cancer-Associated Systemic
Sclerosis: Comment on the Article by Shah et al.
PMID- 28426926
TI - Sorbent material characterization using in-tube extraction needles as inverse gas
chromatography column.
AB - In-tube extraction is a full automated enrichment technique that consists of a
stainless-steel needle, packed with sorbent material for the extraction of
volatile and semivolatile compounds. In principle, all particulate sorbents used
for enrichment in air or headspace analysis can be used. However, the selection
of the sorbents is merely based on empirical considerations rather than on
experimental data, which is caused by a lack of knowledge about the relevant
physicochemical properties of the sorbent. Especially, the knowledge of
hydrostatic, advective, diffusive, and dispersion mechanisms in addition to
sorption enthalpies are important for combined transport and sorption models. To
provide these missing parameters, we developed and evaluated a method in which an
ordinary in-tube extraction needle was employed directly as column for sorbent
characterization by inverse gas chromatography. As probe compounds, benzene,
ethyl acetate, and 3-methyl-1-butanol were used to determine thermodynamic
parameters such as sorption enthalpy, partitioning constant between the solid and
gas phase, and kinetic parameters such as the diffusion coefficient, dispersion
coefficient, and apparent permeability, exemplarily. As sorbent, three
commercially available phases were characterized to demonstrate the applicability
of the method.
PMID- 28426927
TI - Severe, Drug-Resistant OCD Successfully Treated With rTMS and Concomitant
Multidisciplinary Psychotherapy: It's Not Only About the Coil.
PMID- 28426928
TI - Improvement of Escitalopram-Induced Sweating With Citalopram.
PMID- 28426929
TI - Exerting Enhanced Permeability and Retention Effect Driven Delivery by Ultrafine
Iron Oxide Nanoparticles with T1-T2 Switchable Magnetic Resonance Imaging
Contrast.
AB - Poor delivery efficiency remains a major challenge in nanomaterial-based tumor
targeted imaging and drug delivery. This work demonstrates a strategy to improve
nanoparticle delivery and intratumoral distribution using sub-5 nm (3.5 nm core
size) ultrafine iron oxide nanoparticles (uIONP) that can easily extravasate from
the tumor vasculature and readily diffuse into the tumor tissue compared to the
iron oxide nanoparticle (IONP) with larger sizes, followed by self-assembling in
the acidic tumor interstitial space to limit their re-entering into circulation.
By combining enhanced extravasation and reduced intravasation, we achieved
improved delivery and tumor retention of nanoparticles. Multiphoton imaging of
mice bearing orthotopic tumors co-injected with fluorescent dye-labeled
nanoparticles with different sizes showed that uIONPs exhibited more efficient
extravasation out of tumor vessels and penetrated deeper into the tumor than
larger sized IONP counterparts. Moreover, in vivo magnetic resonance imaging
revealed that uIONPs exhibited "bright" T1 contrast when dispersed in the tumor
vasculature and peripheral area at 1 h after intravenous administration, followed
by emerging "dark" T2 contrast in the tumor after 24 h. Observed T1-T2 contrast
switch indicated that uIONPs single-dispersed in blood with T1 contrast may self
assemble into larger clusters with T2 contrast after entering the tumor
interstitial space. Improved passive targeting and intratumoral delivery along
with increased tumor retention of uIONPs are due to both easy extravasation into
the tumor when single-dispersed and restricting intravasation back into
circulation after forming clusters, thus exerting the enhanced permeability and
retention effect for nanoparticle delivery to tumors.
PMID- 28426930
TI - Subcomponent Exchange Transforms an FeII4L4 Cage from High- to Low-Spin,
Switching Guest Release in a Two-Cage System.
AB - Subcomponent exchange transformed new high-spin FeII4L4 cage 1 into previously
reported low-spin FeII4L4 cage 2: 2-formyl-6-methylpyridine was ejected in favor
of the less sterically hindered 2-formylpyridine, with concomitant high- to low
spin transition of the cage's FeII centers. High-spin 1 also reacted more readily
with electron-rich anilines than 2, enabling the design of a system consisting of
two cages that could release their guests in response to combinations of
different stimuli. The addition of p-anisidine to a mixture of high-spin 1 and
previously-reported low-spin FeII4L6 cage 3 resulted in the destruction of 1 and
the release of its guest. However, initial addition of 2-formylpyridine to an
identical mixture of 1 and 3 resulted in the transformation of 1 into 2; added p
anisidine then reacted preferentially with 3 releasing its guest. The addition of
2-formylpyridine thus modulated the system's behavior, fundamentally altering its
response to the subsequent signal p-anisidine.
PMID- 28426931
TI - Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators
and Downregulators with Subtype-Specific ERalpha and ERbeta Activity.
AB - Estrogen receptor alpha (ERalpha) is an important target for the design of drugs
such as tamoxifen (2a) and fulvestrant (5). Three series of ER-ligands based on
the benzoxepin scaffold structure were synthesized: series I containing an
acrylic acid, series II with an acrylamide, and series III with a saturated
carboxylic acid substituent. These compounds were shown to be high affinity
ligands for the ER with nanomolar IC50 binding values. Series I acrylic acid
ligands were generally ERalpha selective. In particular, compound 13e featuring a
phenylpenta-2,4-dienoic acid substituent was shown to be antiproliferative and
downregulated ERalpha and ERbeta expression in MCF-7 breast cancer cells.
Interestingly, from series III, the phenoxybutyric acid derivative compound 22
was not antiproliferative and selectively downregulated ERbeta. A docking study
of the benzoxepin ligands was undertaken. Compound 13e is a promising lead for
development as a clinically relevant SERD, while compound 22 will be a useful
experimental probe for helping to elucidate the role of ERbeta in cancer cells.
PMID- 28426932
TI - Recycling Strategy for Fabricating Low-Cost and High-Performance Carbon Nanotube
TFT Devices.
AB - High-purity semiconducting single-walled carbon nanotubes (s-SWNTs) can be
obtained by conjugated polymer wrapping. However, further purification of sorted
s-SWNTs and high costs of raw materials are still challenges to practical
applications. It is inevitable that a lot of polymers still cover the surface of
s-SWNTs after separation, and the cost of the polymer is relatively higher than
that of SWNTs. Here, we demonstrated a facile isolated process to improve the
quality of s-SWNT solutions and films significantly. Compared with the untreated
s-SWNTs, the contact resistance between the s-SWNT and the electrode is reduced
by 20 times, and the thin-film transistors show 300% enhancement of current
density. In this process, most of the polymers can be recycled and reused
directly without any purification, which can greatly decrease the cost for s-SWNT
separation. The results presented herein demonstrate a new scalable and low-cost
approach for large-scale application of s-SWNTs in the electronics industry.
PMID- 28426933
TI - Triggering Assembly and Disassembly of a Supramolecular Cage.
AB - A novel supramolecular cage built from the self-assembly of tris(2
pyridylmethyl)amine zinc complexes through imine condensation chemistry is
reported. The cage recognition properties over a variety of structurally related
guests, together with the kinetic study of the template assembly and disassembly,
have been investigated in detail. This knowledge has been used to selectively
modulate the rate of both assembly and disassembly processes. In particular, a
novel disassembly method induced by strain release of the guest has been
developed.
PMID- 28426934
TI - From Permeation to Cluster Arrays: Graphene on Ir(111) Exposed to Carbon Vapor.
AB - Our scanning tunneling microscopy and X-ray photoelectron spectroscopy
experiments along with first-principles calculations uncover the rich
phenomenology and enable a coherent understanding of carbon vapor interaction
with graphene on Ir(111). At high temperatures, carbon vapor not only permeates
to the metal surface but also densifies the graphene cover. Thereby, in addition
to underlayer graphene growth, upon cool down also severe wrinkling of the
densified graphene cover is observed. In contrast, at low temperatures the
adsorbed carbon largely remains on top and self-organizes into a regular array of
fullerene-like, thermally highly stable clusters that are covalently bonded to
the underlying graphene sheet. Thus, a new type of predominantly sp2-hybridized
nanostructured and ultrathin carbon material emerges, which may be useful to
encage or stably bind metal in finely dispersed form.
PMID- 28426935
TI - Manipulation of Mg2+-Ca2+ Switch on the Development of Bone Mimetic
Hydroxyapatite.
AB - Ionic substitution can affect essential physicochemical properties leading to a
specific biological behavior upon implantation. Therefore, it has been proposed
as a tool to increase the biological efficiency of calcium phosphate based
materials. In the following study, we have evaluated the contribution of an
important cation in nature, Mg2+, into the structure of previously studied
biocompatible and biodegradable hydroxyapatite (HA) nanorods and its subsequent
effect on its chemical, morphology, and bone mimetic articulation. Mg2+
substituted HA samples were synthesized by an aqueous wet-chemical precipitation
method, followed by an hydrothermal treatment involving a Mg2+ precursor that
partially replace Ca2+ ions into HA crystal lattice; Mg2+ concentrations were
modulated to obtain a nominal composition similar to that exists in calcified
tissues. Hydrothermally synthesized Mg2+-substituted HA nanoparticles were
characterized by X-ray powder diffraction, FT-NIR and EDX spectroscopies, field
emission scanning and high resolution transmission electron microscopies (FE-SEM,
H-TEM). Molecular modeling combining ab initio methods and power diffraction data
were also performed. Results showed that Mg2+-substitution promoted the formation
of calcium deficient HA (cdHA) where Mg2+ replacement is energetically favored at
Ca(1) position in a limited and specific amount directing the additional Mg2+
toward the surface of the crystal. The control of Mg2+ incorporation into HA
nanorods gave rise to a tailored crystallinity degree, cell parameters,
morphology, surface hydration, solubility, and degradation properties in a dose
replacement dependent manner. The obtained materials show qualities that
conjugated together to drive an optimal in vitro cellular viability, spreading,
and proliferation confirming their biocompatibility. In addition, an improved
adhesion of osteoblast was evidenced after Mg2+-Ca2+ substitution.
PMID- 28426936
TI - Cholesterol-Assisted Bacterial Cell Surface Engineering for Photodynamic
Inactivation of Gram-Positive and Gram-Negative Bacteria.
AB - Antibacterial photodynamic therapy (PDT), which enables effective killing of
regular and multidrug-resistant (MDR) bacteria, is a promising treatment modality
for bacterial infection. However, because most photosensitizer (PS) molecules
fail to strongly interact with the surface of Gram-negative bacteria, this
technique is suitable for treating only Gram-positive bacterial infection, which
largely hampers its practical applications. Herein, we reveal for the first time
that cholesterol could significantly facilitate the hydrophobic binding of PSs to
the bacterial surface, achieving the hydrophobic interaction-based bacterial cell
surface engineering that could effectively photoinactivate both Gram-negative and
Gram-positive bacteria. An amphiphilic polymer composed of a polyethylene glycol
(PEG) segment terminated with protoporphyrin IX (PpIX, an anionic PS) and
cholesterol was constructed (abbreviated Chol-PEG-PpIX), which could self
assemble into micelle-like nanoparticles (NPs) in aqueous solution. When
encountering the Gram-negative Escherichia coli cells, the Chol-PEG-PpIX NPs
would disassemble and the PpIX moieties could effectively bind to the bacterial
surface with the help of the cholesterol moieties, resulting in the significantly
enhanced fluorescence emission of the bacterial surface. Under white light
irradiation, the light-triggered singlet oxygen (1O2) generation of the membrane
bound PpIX could not only severely damage the outer membrane but also facilitate
the entry of external Chol-PEG-PpIX into the bacteria, achieving >99.99%
bactericidal efficiency. Besides, as expected, the Chol-PEG-PpIX NPs also
exhibited excellent antibacterial performance against the Gram-positive
Staphylococcus aureus. We also verified that this nanoagent possesses negligible
dark cytotoxicity toward mammalian cells and good hemocompatibility. To the best
of our knowledge, this study demonstrates for the first time the feasibility of
constructing a fully hydrophobic interaction-based and outer membrane-anchored
antibacterial PDT nanoagent.
PMID- 28426937
TI - High-Throughput Quantitative Intrinsic Thiol Reactivity Evaluation Using a
Fluorescence-Based Competitive Endpoint Assay.
AB - In a high-throughput screening (HTS) process, the chemical reactivity of test
samples should be carefully examined because such reactive compounds may lead to
false-positive results and adverse effects in vivo. Among all natural amino
acids, the thiol side chain in cysteine has the highest nucleophilicity; thus,
assessment of intrinsic thiol group reactivity in the HTS processes is expected
to accelerate drug discovery. In general, kchem (M-1s-1), the secondary reaction
rate constant of a compound to thiol, can be evaluated via time course
measurements of thiol-compound adducts using liquid chromatography-mass
spectroscopy; this requires time-consuming and labor-intensive procedures. To
overcome this issue, we developed a fluorescence-based competitive endpoint assay
that allows quantitative calculation of the reaction rate of test compounds in an
HTS format. Our assay is based on the competitive reaction for a free thiol
(e.g., glutathione) between the test compounds and a fluorescent probe, o
maleimide BODIPY. Our assay provides robust data with a satisfactory throughput
at an affordable cost. Our kchem evaluation method has advantages over previous
assays in terms of higher throughput and quantitativeness. Thus, it contributes
to early elimination of reactive compounds as well as quantitative evaluation of
the kchem values of covalent inhibitors.
PMID- 28426938
TI - High-Throughput Screening to Identify Inhibitors of DEAD Box Helicase DDX41.
AB - The human DEAD (Asp-Glu-Ala-Asp) box protein DDX41, a member of the DEXDc
helicase family, has nucleic acid-dependent ATPase and RNA and DNA translocase
and unwinding activities. DDX41 is affected by somatic mutations in sporadic
cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients
with germline DDX41 mutations. The R525H mutation in DDX41 is thought to play
important roles in the development of hereditary myelodysplastic syndrome and
acute myelocytic leukemia. In this study, human DDX41 and its R525H mutant
(R525H) were expressed in Escherichia coli and purified. The ATPase activities of
the recombinant DDX41 and R525H proteins were dependent on both ATP and double
stranded DNA (dsDNA), such as poly(dG-dC) and poly(dA-dT). High-throughput
screening was performed with a dsDNA-dependent ATPase assay using the human R525H
proteins. After hit confirmation and counterscreening, several small-molecule
inhibitors were successfully identified. These compounds show DDX41-selective
inhibitory activities.
PMID- 28426939
TI - High-Throughput Agonist Shift Assay Development for the Analysis of M1-Positive
Allosteric Modulators.
AB - Agonist shift assays feature cross-titrations of allosteric modulators and
orthosteric ligands. Information generated in agonist shift assays can include a
modulator's effect on the orthosteric agonist's potency (alpha) and efficacy
(beta), as well as direct agonist activity of the allosteric ligand (tauB) and
the intrinsic binding affinity of the modulator to the unoccupied receptor (KB).
Because of the heavy resource demand and complex data handling, these allosteric
parameters are determined infrequently during the course of a drug discovery
program and on a relatively small subset of compounds. Automation of agonist
shift assays enables this data-rich analysis to evaluate a larger number of
compounds, offering the potential to differentiate compound classes earlier and
prospectively prioritize based on desired molecular pharmacology. A high
throughput calcium-imaging agonist shift assay was pursued to determine the
allosteric parameters of over 1000 positive allosteric modulator (PAM) molecules
for the human muscarinic acetylcholine receptor 1 (M1). Control compounds were
run repeatedly to demonstrate internal consistency. Comparisons between potency
measurements and the allosteric parameter results demonstrate that these
different types of measurements do not necessarily correlate, highlighting the
importance of fully characterizing and understanding the allosteric properties of
leads.
PMID- 28426940
TI - Prospective Assessment of Virtual Screening Heuristics Derived Using a Novel
Fusion Score.
AB - High-throughput screening (HTS) is a widespread method in early drug discovery
for identifying promising chemical matter that modulates a target or phenotype of
interest. Because HTS campaigns involve screening millions of compounds, it is
often desirable to initiate screening with a subset of the full collection.
Subsequently, virtual screening methods prioritize likely active compounds in the
remaining collection in an iterative process. With this approach, orthogonal
virtual screening methods are often applied, necessitating the prioritization of
hits from different approaches. Here, we introduce a novel method of fusing these
prioritizations and benchmark it prospectively on 17 screening campaigns using
virtual screening methods in three descriptor spaces. We found that the fusion
approach retrieves 15% to 65% more active chemical series than any single machine
learning method and that appropriately weighting contributions of similarity and
machine-learning scoring techniques can increase enrichment by 1% to 19%. We also
use fusion scoring to evaluate the tradeoff between screening more chemical
matter initially in lieu of replicate samples to prevent false-positives and find
that the former option leads to the retrieval of more active chemical series.
These results represent guidelines that can increase the rate of identification
of promising active compounds in future iterative screens.
PMID- 28426941
TI - Behavioral deficits and neural damage of Caenorhabditis elegans induced by three
rare earth elements.
AB - Rare earth elements (REEs) are widely used in industry, agriculture, medicine and
daily life in recent years. However, environmental and health risks of REEs are
still poorly understood. In this study, neurotoxicity of trichloride neodymium,
praseodymium and scandium were evaluated using nematode Caenorhabditis elegans as
the assay system. Median lethal concentrations (48 h) were 99.9, 157.2 and 106.4
mg/L for NdCl3, PrCl3 and ScCl3, respectively. Sublethal dose (10-30 mg/L) of
these trichloride salts significantly inhibited body length of nematodes. Three
REEs resulted in significant declines in locomotor frequency of body bending,
head thrashing and pharyngeal pumping. In addition, mean speed and wavelength of
crawling movement were significantly reduced after chronic exposure. Using
transgenic nematodes, we found NdCl3, PrCl3 and ScCl3 resulted in loss of
dendrite and soma of neurons, and induced down-expression of dat-1::GFP and unc
47::GFP. It indicates that REEs can lead to damage of dopaminergic and GABAergic
neurons. Our data suggest that exposure to REEs may cause neurotoxicity of
inducing behavioral deficits and neural damage. These findings provide useful
information for understanding health risk of REE materials.
PMID- 28426943
TI - How strong is the evidence for using blood biomarkers alone to screen for alcohol
consumption during pregnancy? A systematic review.
AB - Accurate and early identification of women at risk from alcohol consumption
during pregnancy allows education and support programmes to be targeted at those
most in need. We aimed to conduct a systematic review to compare the efficacy of
blood analysis and maternal self-report in detecting at risk women during
pregnancy. This review investigated diagnostic accuracy. We searched four
databases (Medline, Embase, Psychinfo and CINAHL) for relevant articles and
conducted hand searches of recent issues of key journals in the field. No
restriction was placed on inclusion in terms of publication date or language.
Studies were deemed eligible if they were original research and included a direct
comparison of the results of blood biomarker analysis and self-reported alcohol
use for the detection of alcohol consumption in pregnant women. Quality appraisal
of included studies was conducted using the QUADAS II tool. Eight studies met the
inclusion criteria. Gamma-glutamyltransferase (GGT) was investigated in five
studies, mean corpuscular volume (MCV) and phosphatidylethanol (PEth) in three
studies and carbohydrate deficient transferrin (CDT), aspartate aminotransferase
(AST), alanine aminotransferase (ALT) and whole blood associated acetaldehyde
assay (WBAA) were each investigated in two studies. Although all of the studies
were rated of good methodological quality, none of the biomarkers had both high
sensitivity and specificity when compared to self-report. There was some evidence
that a combination of biomarkers, or combining biomarkers with self-report,
increases accuracy. In summary, the blood biomarkers examined were of limited use
in screening for low and moderate alcohol consumption in pregnancy when compared
to self-report. However, certain biomarkers, such and CDT and PEth may complement
self-report and help improve the accuracy of diagnosis.
PMID- 28426942
TI - Polychlorinated biphenyl and polybrominated diphenyl ether profiles in serum from
cattle, sheep, and goats across California.
AB - It has been previously been shown by our lab and others that persistent organic
pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl
ethers (PBDEs), are contaminants in milk produced for human consumption. To
further this research we determined the concentration of 21 PCB and 14 PBDE
congeners in livestock serum, mainly bovine, across California. Congeners were
extracted from serum using solid phase extraction (SPE), cleaned up by silica
cartridge and quantified using gas chromatography-triple quadruple mass
spectrometry. We detected significant differences among species and the
production class of cattle (beef or dairy). The sum of all 21 PCB congeners
(SigmaPCBs) in caprine and ovine sera had a mean value of 9.26 and 9.13 ng/mL,
respectively, compared to 3.98 ng/mL in bovine sera. The mean value for the sum
of all 14 PBDE congeners (SigmaPBDEs) in caprine and ovine sera was 2.82 and 2.39
ng/mL, respectively, compared to 0.91 ng/mL in bovine sera. Mean SigmaPCBs in
dairy cattle was 5.92 ng/mL compared to 2.70 ng/mL in beef cattle. Mean
SigmaPBDEs in dairy cattle was 1.33 ng/mL compared to 0.70 ng/mL in beef cattle.
There were no regional differences in the SigmaPCBs or SigmaPBDEs in cattle
distributed across California. These results highlight the fact that livestock
are still being exposed to these pollutants yet little is known about where this
exposure may be coming from.
PMID- 28426944
TI - A comparison between reduced-port robotic surgery and multiport robot-assisted
laparoscopy for myomectomy.
AB - OBJECTIVE: To compare the surgical outcomes between reduced-port robotic surgery
(RPRS) using the Octo-Port channel and multiport robot-assisted laparoscopy for
myomectomy. STUDY DESIGN: This prospective study compared and analyzed data from
15 consecutive women who underwent RPRS for myomectomy and 15 consecutive women
who underwent multiport robot-assisted laparoscopy to treat symptomatic uterine
myoma from January 2016 to June 2016. The patients were treated by two surgeons
at two institutions. RESULTS: The two study groups did not differ
demographically. The differences in surgical outcomes, such as docking time,
console time, hospital stay, estimated blood loss, Hb change, myoma count, and
weight, also did not differ between the two groups. On the contrary, the number
of port site was only 2 in RPRS compared with 4-5 in multiport robot-assisted
laparoscopic myomectomy. CONCLUSION: RPRS for myomectomy seems technically
feasible and safe, with short-term perioperative outcomes similar to those from
multiport robot-assisted laparoscopic myomectomy.
PMID- 28426945
TI - Testosterone levels in healthy men correlate negatively with serotonin 4 receptor
binding.
AB - The serotonergic system integrates sex steroid information and plays a central
role in mood and stress regulation, cognition, appetite and sleep. This interplay
may be critical for likelihood of developing depressive episodes, at least in a
subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes
central serotonergic tonus, which may be related to endogenous sex-steroid levels
in the mentally healthy state even though this remains elusive. Here we evaluate
if peripheral levels of estradiol and testosterone are associated with 5-HT4R
binding as imaged by [11C]SB207145 positron emission tomography in a group of 41
healthy men. We estimated global 5-HT4R binding using a latent variable model
framework, which models shared correlation between 5-HT4R across multiple brain
regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus,
pallidostriatum and neocortex). We tested whether testosterone and estradiol
predict global 5-HT4R, adjusting for age. We found that testosterone, but not
estradiol, correlated negatively with global 5-HT4R levels (p=0.02) suggesting
that men with high levels of testosterone have higher cerebral serotonergic
tonus. Our findings corroborate the link between sex hormone levels and serotonin
signalling. Future longitudinal studies in clinical relevant populations are
needed to elucidate the potential importance of testosterone in the
pathophysiology of e.g. major depression and its treatment.
PMID- 28426946
TI - Quantification of rubidium as a trace element in beef using laser induced
breakdown spectroscopy.
AB - This study evaluates the potential of laser induced breakdown spectroscopy (LIBS)
coupled with chemometrics to develop a quantification model for rubidium (Rb) in
minced beef. A LIBSCAN 150 system was used to collect LIBS spectra of minced beef
samples. Beef liver was used to spike the Rb levels in minced beef. All samples
were dried, powdered and pelleted using a hydraulic press. Measurements were
conducted by scanning 100 different locations with an automated XYZ sample
chamber. Partial least squares regression (PLSR) was used to develop the
calibration model, yielding a calibration coefficient of determination (Rc2) of
0.99 and a root mean square error of calibration (RMSEC) of 0.05ppm. The model
also showed good results with leave-one-out cross validation, yielding a cross
validation coefficient of determination (Rcv2) of 0.90 and a root mean square
error of cross-validation (RMSECV) of 0.22ppm. The current study shows the
potential of LIBS as a rapid analysis tool for the meat processing industry.
PMID- 28426947
TI - Structural neuroplasticity of the superior temporal plane in early and late
blindness.
AB - Blindness is associated with well-documented changes to the morphometry and
function of the occipital cortex. By comparison, its impact on the perisylvian
regions in the superior temporal plane (STP) is poorly understood, with many
studies reporting null findings on this issue. Here we re-approach this question
using a morphometric analysis that relied on fine-scale, manual annotation of 13
sub-regions within the STP and that quantified both univariate and multivariate
differences in morphometry. We applied these analyses to both cortical thickness
(CT) and surface area (SA) data from congenitally and late blind, as compared to
two matched sighted control groups. The univariate analyses indicated that for
CT, no region differentiated blind from sighted, and for SA, two regions showed
lower values for congenitally blind. Moreover, the multivariate analyses
identified more robust signatures of plasticity in blindness. Specifically,
pairwise regional correlations of CT values between contralateral regions were
significantly higher for both blind groups as compared to sighted controls. A
similar pattern for SA data was found for congenitally blind alone. Our findings
indicate that blindness strongly impacts STP, resulting in a more coordinated
pattern of interhemispheric morphometric development. We discuss implications for
theories of language plasticity and models of neuroplasticity in the blind.
PMID- 28426948
TI - Digit ratio (2D:4D) and handgrip strength are correlated in women (but not in
men) in Hui ethnicity.
AB - INTRODUCTION: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is
used as a biomarker of prenatal testosterone exposure and was found associated
with physical ability, such as handgrip strength (HGS). Recently, this
association has been discussed in several ethnic groups. AIMS: To investigate
correlations between 2D:4D and HGS in Chinese population of Ningxia Hui
ethnicity. METHODS: Here we firstly present the evidence on digit ratio and HGS
of 346 college students (119 males and 227 females) by collecting photographs and
HGS of both hands at Yinchuan city, in the Ningxia province of China. RESULTS:
Females have higher mean values of digit ratio than males; significant variances
of 3D:5D (left and right: P<0.05), 2D:3D, 3D:4D (left and right: P<0.01) and
2D:4D, 2D:5D (left and right: P<0.001) were found between different sex. Males
showed significantly greater HGS than females on both hands. 2D:4D of both hands
were significantly negative correlated with HGS in females (but not in males).
CONCLUSIONS: 2D:4D ratio is negatively correlated with HGS in a Chinese
population (especially in females) of Ningxia Hui ethnicity.
PMID- 28426949
TI - Agarra, agarran: Evidence of early comprehension of subject-verb agreement in
Spanish.
AB - Studies across many languages (e.g., Dutch, English, Farsi, Spanish, Xhosa) have
failed to show early acquisition of subject-verb (SV) agreement, whereas recent
studies on French reveal acquisition by 30months of age. Using a similar
procedure as in previous French studies, the current study evaluated whether
earlier comprehension of SV agreement in (Mexican) Spanish can be revealed when
task demands are lowered. Two experiments using a touch-screen pointing task
tested comprehension of SV agreement by monolingual Spanish-speaking children
growing up in Mexico City between about 3 and 5years of age. In Experiment 1, the
auditory stimuli consisted of a transitive verb+pseudonoun object (e.g., agarra
el micho 'he throws the micho' vs. agarran el duco 'they throw the duco');
results failed to show early comprehension of SV agreement, replicating previous
findings. In Experiment 2, the same stimuli were used, with the crucial
difference that the word objeto 'object' replaced all pseudonouns; results
revealed SV agreement comprehension as early as 41 to 50months. Taken together,
our findings show that comprehension at this age is facilitated when task demands
are lowered, here by not requiring children to process pseudowords (even when
these were not critical to the task). Hence, these findings underscore the
importance of task-specific/stimulus-specific features when testing early
morphosyntactic development and suggest that previous results may have
underestimated Spanish-speaking children's competence.
PMID- 28426950
TI - Testing the validity of a continuous false belief task in 3- to 7-year-old
children.
AB - In two studies, we examined young children's performance on the paper-and-pencil
version of the Sandbox task, a continuous measure of false belief, and its
relations with other false belief and inhibition tasks. In Study 1, 96 children
aged 3 to 7years completed three false belief tasks (Sandbox, Unexpected
Contents, and Appearance/Reality) and two inhibition tasks (Head-Shoulders-Knees
Toes and Grass/Snow). Results revealed that false belief bias-a measure of
egocentrism-on the Sandbox task correlated with age but not with the Unexpected
Contents or Appearance/Reality task or with measures of inhibition after
controlling for age. In Study 2, 90 3- to 7-year-olds completed five false belief
tasks (Sandbox, Unexpected Contents, Appearance/Reality, Change of Location, and
a second-order false belief task), two inhibition tasks (Simon Says and
Grass/Snow), and a receptive vocabulary task (Peabody Picture Vocabulary Test).
Results showed that false belief bias on the Sandbox task correlated negatively
with age and with the Change of Location task but not with the other false belief
or inhibition tasks after controlling for age and receptive vocabulary. The
Sandbox task shows promise as an age-sensitive measure of false belief
performance during early childhood and shows convergent and discriminant
validity.
PMID- 28426951
TI - Temperature induced self-assembly of amino acid-derived vinyl block copolymers
via dual phase transitions.
AB - The unique thermoresponsive phase behaviors of diblock copolymers from amino acid
derived vinyl monomers have been demonstrated in view of variation in the
aggregation state in water. Amino acid-based block copolymers composed of N
acryloyl-Ala-methylester (NAAMe) and N-acryloyl-betaAla-methylester (NAbetaAMe)
are successfully synthesized by RAFT polymerization. The resultant block
copolymers poly(NAAMe48-b-NAbetaAMem) contain a constant degree of polymerization
(DP=48) of the poly(NAAMe) block, but the DP of the poly(NAbetaAMe) block varies
(m=80-122). The turbidimetry subjected to these copolymer aqueous solutions
exhibits two LCST transitions upon heating. In the 1st LCST region, the block
copolymer forms a relatively loose-molecular packing, while large aggregates due
to partial dehydration of polymer molecules, which subsequently transform into a
stable micelle structure in a region of 30-39 degrees C. Finally, a tight
aggregate composed of the dehydrated micelles is formed. Temperature-dependent 1H
NMR spectroscopy of the diblock copolymers also supports such a postulation for
the dual phase transitions and stable micelle structure formation. In addition, a
typical salting-out effect is observed in the thermal behavior of the polymer,
but a serious cytotoxic effect is not observed in NIH/3T3 cells, suggesting that
the novel diblock copolymers are relevant for biomedical applications.
PMID- 28426952
TI - Plant viruses and bacteriophages for drug delivery in medicine and biotechnology.
AB - There are a wide variety of synthetic and naturally occurring nanomaterials under
development for nanoscale cargo-delivery applications. Viruses play a special
role in these developments, because they can be regarded as naturally occurring
nanomaterials evolved to package and deliver cargos. While any nanomaterial has
its advantage and disadvantages, viral nanoparticles (VNPs), in particular the
ones derived from plant viruses and bacteriophages, are attractive options for
cargo-delivery as they are biocompatible, biodegradable, and non-infectious to
mammals. Their protein-based structures are often understood at atomic resolution
and are amenable to modification with atomic-level precision through chemical and
genetic engineering. Here we present a focused review of the emerging technology
development of plant viruses and bacteriophages targeting human health and
agricultural applications. Key target areas of development are their use in
chemotherapy, photodynamic therapy, pesticide-delivery, gene therapy, vaccine
carriers, and immunotherapy.
PMID- 28426953
TI - MethyLock: DNA Demethylation Is the Epigenetic Key to Axon Regeneration.
AB - In this issue of Neuron, Weng et al. (2017) reveal a role for active DNA
demethylation in allowing axon regeneration to occur in the mature nervous system
following axonal injury.
PMID- 28426954
TI - Neuronal Polarity: MAP2 Shifts Secretory Vesicles into High Gear for Long-Haul
Transport down the Axon.
AB - Accurate control of polarized cargo trafficking is essential for neuronal
function. In this issue of Neuron, Gumy et al. (2017) show that MAP2 defines a
pre-axonal filtering zone and controls axonal cargo transport by influencing the
activities of distinct kinesin motors.
PMID- 28426955
TI - The Small World of a Fear Memory.
AB - How are fear memories organized? In this issue of Neuron, Vetere et al. (2017)
take a network-based approach to demonstrate the importance of highly
interconnected hub regions in the consolidation of a fear memory. By doing so,
they provide an elegant framework for predicting behavior from functional network
properties.
PMID- 28426956
TI - Amines, Astrocytes, and Arousal.
AB - Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and
reward in the CNS. New data suggest that, from flies to mammals, a major
mechanism for amine transmitter action is to raise astrocyte [Ca2+]i and release
gliotransmitters that modulate neuronal activity and behavior.
PMID- 28426957
TI - Emerging Global Initiatives in Neurogenetics: The Enhancing Neuroimaging Genetics
through Meta-analysis (ENIGMA) Consortium.
AB - The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is
a global team science effort, now including over 800 scientists spread across 340
institutions in 35 countries, with the shared goal of understanding disease and
genetic influences on the brain. This "crowdsourcing" approach to team
neuroscience has unprecedented power for advancing our understanding of both
typical and atypical human brain development.
PMID- 28426958
TI - Elucidating the Role of TREM2 in Alzheimer's Disease.
AB - Alzheimer's disease (AD) is the sixth leading cause of death in the United States
and the most common cause of dementia in the elderly. Genetic factors, such as
rare variants in the microglial-expressed gene TREM2, strongly impact the
lifetime risk of developing AD. Several recent studies have described dramatic
TREM2-dependent phenotypes in mouse models of amyloidosis that point to an
important role for TREM2 in regulating the response of the innate immune system
to Abeta pathology. Furthermore, elevations in the CSF levels of soluble TREM2
fragments implicate changes in inflammatory pathways as occurring coincident with
markers of neuronal damage and the onset of clinical dementia in AD. Here, we
review the rapidly developing literature surrounding TREM2 in AD that may provide
novel insight into the broader role of the innate immune system in
neurodegenerative disease.
PMID- 28426959
TI - Ontogenesis of Lateralization.
AB - The brains of humans and other animals are asymmetrically organized, but we still
know little about the ontogenetic and neural fundaments of lateralizations. Here,
we review the current state of understanding about the role of genetic and non
genetic factors for the development of neural and behavioral asymmetries in
vertebrates. At the genetic level, the Nodal signaling cascade is of central
importance, but several other genetic pathways have been discovered to also shape
the lateralized embryonic brain. Studies in humans identified several relevant
genes with mostly small effect sizes but also highlight the extreme importance of
non-genetic factors for asymmetry development. This is also visible in visual
asymmetry in birds, in which genes only affect embryonic body position, while the
resulting left-right difference of visual stimulation shapes visual pathways in a
lateralized way. These and further studies in zebrafish and humans highlight that
the many routes from genes to asymmetries of function run through left-right
differences of neural pathways. They constitute the lateralized blueprints of our
perception, cognition, and action.
PMID- 28426960
TI - Editorial Note to: Endogenous Piezo1 Can Confound Mechanically Activated Channel
Identification and Characterization.
PMID- 28426961
TI - Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and
Characterization.
AB - A gold standard for characterizing mechanically activated (MA) currents is via
heterologous expression of candidate channels in naive cells. Two recent studies
described MA channels using this paradigm. TMEM150c was proposed to be a
component of an MA channel partly based on a heterologous expression approach
(Hong et al., 2016). In another study, Piezo1's N-terminal "propeller" domain was
proposed to constitute an intrinsic mechanosensitive module based on expression
of a chimera between a pore-forming domain of the mechanically insensitive ASIC1
channel and Piezo1 (Zhao et al., 2016). When we attempted to replicate these
results, we found each construct conferred modest MA currents in a small fraction
of naive HEK cells similar to the published work. Strikingly, these MA currents
were not detected in cells in which endogenous Piezo1 was CRISPR/Cas9
inactivated. These results highlight the importance of choosing cells lacking
endogenous MA channels to assay the mechanotransduction properties of various
proteins. This Matters Arising paper is in response to Hong et al. (2016) and
Zhao et al. (2016) in Neuron. See also the response papers by Hong et al. (2017)
and Zhao et al. (2017) published concurrently with this Matters Arising.
PMID- 28426962
TI - Evidence for Mechanosensitive Channel Activity of Tentonin 3/TMEM150C.
AB - Mechanosensation is essential for various physiological processes, and it is
mediated by mechanotransduction channels. Recently, we reported that
TMEM150C/Tentonin 3 (TTN3) confers mechanically activated currents with slow
inactivation kinetics in several cell types, including dorsal root ganglion
neurons (Hong et al., 2016). The accompanying Matters Arising by Dubin, Murthy,
and colleagues confirms that naive heterologous cells demonstrate a mechanically
activated current, but finds that this response is absent in CRISPR-Cas9 Piezo1
knockout cell lines and suggests that TTN3 is a modulator of Piezo1. We present
and discuss evidence based on co-expression of TTN3 and Peizo1 and mutant
variants of the pore region of TTN3 to support that TTN3 is a pore-forming unit,
not an amplifying adaptor for Piezo1 activity. This Matters Arising Response
paper, along with Zhao et al. (2017), addresses the Matters Arising from Dubin et
al. (2017), published concurrently in this issue of Neuron.
PMID- 28426963
TI - Heterologous Expression of the Piezo1-ASIC1 Chimera Induces Mechanosensitive
Currents with Properties Distinct from Piezo1.
AB - Piezo1 represents a prototype of the mammalian mechanosensitive cation channel,
but its molecular mechanism remains elusive. In a recent study, we showed that C
terminal region, which contains the last two TMs, of 2189-2547 of Piezo1 forms
the bona fide pore module, and systematically identified the pore-lining helix
and key pore-property-determining residues (Zhao et al., 2016). Furthermore, we
have engineered the Piezo1(1-2190)-ASIC1 chimera (fusing the N-terminal region of
1-2190 to the mechano-insensitive ASIC1) that mediated mechanical- and acid
evoked currents in HEK293T cells, indicating the sufficiency of the N-terminal
region in mechanotransduction. Now in a Matters Arising, the authors specifically
questioned the implication of the chimera data among the many findings shown in
our paper. They replicated the chimera-mediated mechanosensitive currents in
HEK293T cells that have nearly no detectable expression of endogenous Piezo1, but
paradoxically found the chimera to be less effective in Piezo1 knockout HEK293T
cells, indicating the involvement of endogenous Piezo1. In this Matters Arising
Response, we discuss the chimera results and consider potential interpretations
in light of the Matters Arising from Dubin et al. (2017), published concurrently
in this issue of Neuron. Please see also the response from Hong et al. (2017),
published in this issue.
PMID- 28426964
TI - iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
AB - Microglia play critical roles in brain development, homeostasis, and neurological
disorders. Here, we report that human microglial-like cells (iMGLs) can be
differentiated from iPSCs to study their function in neurological diseases, like
Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to
microglia in vivo, and whole-transcriptome analysis demonstrates that they are
highly similar to cultured adult and fetal human microglia. Functional assessment
of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli,
migrate and undergo calcium transients, and robustly phagocytose CNS substrates.
iMGLs were used to examine the effects of Abeta fibrils and brain-derived tau
oligomers on AD-related gene expression and to interrogate mechanisms involved in
synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human
brain organoids resemble microglia in vivo. Together, these findings demonstrate
that iMGLs can be used to study microglial function, providing important new
insight into human neurological disease.
PMID- 28426965
TI - Formation and Maintenance of Functional Spines in the Absence of Presynaptic
Glutamate Release.
AB - Dendritic spines are the major transmitter reception compartments of
glutamatergic synapses in most principal neurons of the mammalian brain and play
a key role in the function of nerve cell circuits. The formation of functional
spine synapses is thought to be critically dependent on presynaptic glutamatergic
signaling. By analyzing CA1 pyramidal neurons in mutant hippocampal slice
cultures that are essentially devoid of presynaptic transmitter release, we
demonstrate that the formation and maintenance of dendrites and functional spines
are independent of synaptic glutamate release.
PMID- 28426966
TI - Assembly of Excitatory Synapses in the Absence of Glutamatergic
Neurotransmission.
AB - Synaptic excitation mediates a broad spectrum of structural changes in neural
circuits across the brain. Here, we examine the morphologies, wiring, and
architectures of single synapses of projection neurons in the murine hippocampus
that developed in virtually complete absence of vesicular glutamate release.
While these neurons had smaller dendritic trees and/or formed fewer contacts in
specific hippocampal subfields, their stereotyped connectivity was largely
preserved. Furthermore, loss of release did not disrupt the morphogenesis of
presynaptic terminals and dendritic spines, suggesting that glutamatergic
neurotransmission is unnecessary for synapse assembly and maintenance. These
results underscore the instructive role of intrinsic mechanisms in synapse
formation.
PMID- 28426968
TI - MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent
Cargo Transport in Sensory Neurons.
AB - Polarized cargo transport is essential for neuronal function. However, the
minimal basic components required for selective cargo sorting and distribution in
neurons remain elusive. We found that in sensory neurons the axon initial segment
is largely absent and that microtubule-associated protein 2 (MAP2) defines the
cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry
by coordinating the activities of molecular motors. We show that distinct
kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal
cargo trafficking, while kinesin-1 slows down axonal cargo transport. MAP2
inhibits "slow" kinesin-1 motor activity and allows kinesin-3 to drive robust
cargo transport from the soma into the axon. In the distal axon, the inhibitory
action of MAP2 decreases, leading to regained kinesin-1 activity and vesicle
distribution. We propose that selective axonal cargo trafficking requires the
MAP2-defined pre-axonal filtering zone and the ability of cargos to switch
between distinct kinesin motor activities.
PMID- 28426969
TI - Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice.
AB - Behavior depends on coordinated activity across multiple brain regions. Within
such networks, highly connected hub regions are assumed to disproportionately
influence behavioral output, although this hypothesis has not been systematically
evaluated. Previously, by mapping brain-wide expression of the activity-regulated
gene c-fos, we identified a network of brain regions co-activated by fear memory.
To test the hypothesis that hub regions are more important for network function,
here, we simulated node deletion in silico in this behaviorally defined
functional network. Removal of high degree nodes produced the greatest network
disruption (e.g., reduction in global efficiency). To test these predictions in
vivo, we examined the impact of post-training chemogenetic silencing of different
network nodes on fear memory consolidation. In a series of independent
experiments encompassing 25% of network nodes (i.e., 21/84 brain regions), we
found that node degree accurately predicted observed deficits in memory
consolidation, with silencing of highly connected hubs producing the largest
impairments.
PMID- 28426967
TI - An Intrinsic Epigenetic Barrier for Functional Axon Regeneration.
AB - Mature neurons in the adult peripheral nervous system can effectively switch from
a dormant state with little axonal growth to robust axon regeneration upon
injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal
growth competence are not well understood. Here, we show that peripheral sciatic
nerve lesion in adult mice leads to elevated levels of Tet3 and 5
hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3
is required for robust axon regeneration of DRG neurons and behavioral recovery.
Mechanistically, peripheral nerve injury induces DNA demethylation and
upregulation of multiple regeneration-associated genes in a Tet3- and thymine DNA
glycosylase-dependent fashion in DRG neurons. In addition, Pten deletion-induced
axon regeneration of retinal ganglion neurons in the adult CNS is attenuated upon
Tet1 knockdown. Together, our study suggests an epigenetic barrier that can be
removed by active DNA demethylation to permit axon regeneration in the adult
mammalian nervous system.
PMID- 28426970
TI - Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission.
AB - The paraventricular nucleus of the thalamus (PVT) is thought to regulate
behavioral responses under emotionally arousing conditions. Reward-associated
cues activate PVT neurons; however, the specific PVT efferents regulating reward
seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT
activity under two emotionally distinct conditions: (1) when reward was available
during the cue as expected or (2) when reward was unexpectedly omitted during the
cue. Pharmacological inactivation of the anterior PVT (aPVT), but not the
posterior PVT, increased sucrose seeking only when reward was omitted. Consistent
with this, photoactivation of aPVT neurons abolished sucrose seeking, and the
firing of aPVT neurons differentiated reward availability. Photoinhibition of
aPVT projections to the nucleus accumbens or to the amygdala increased or
decreased, respectively, sucrose seeking only when reward was omitted. Our
findings suggest that PVT bidirectionally modulates sucrose seeking under the
negative (frustrative) conditions of reward omission.
PMID- 28426971
TI - Metaplasticity as a Neural Substrate for Adaptive Learning and Choice under
Uncertainty.
AB - Value-based decision making often involves integration of reward outcomes over
time, but this becomes considerably more challenging if reward assignments on
alternative options are probabilistic and non-stationary. Despite the existence
of various models for optimally integrating reward under uncertainty, the
underlying neural mechanisms are still unknown. Here we propose that reward
dependent metaplasticity (RDMP) can provide a plausible mechanism for both
integration of reward under uncertainty and estimation of uncertainty itself. We
show that a model based on RDMP can robustly perform the probabilistic reversal
learning task via dynamic adjustment of learning based on reward feedback, while
changes in its activity signal unexpected uncertainty. The model predicts time
dependent and choice-specific learning rates that strongly depend on reward
history. Key predictions from this model were confirmed with behavioral data from
non-human primates. Overall, our results suggest that metaplasticity can provide
a neural substrate for adaptive learning and choice under uncertainty.
PMID- 28426972
TI - Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors
sensitize cancer stem cells to cisplatin and induces tumor senescence.
PMID- 28426973
TI - Non-linear enhancement of mRNA delivery efficiencies by influenza A derived NS1
protein engendering host gene inhibition property.
AB - Nucleic acid induced immunogenicity remains a significant impediment in
biomedical therapeutics because the innate immune system is a complex network
overlaid with functional redundancies. Herein we report that non-structural
protein 1 (NS1), an immune evasion protein derived from influenza A virus, when
co-delivered in mRNA format is a potent mRNA transfection enhancer without
toxicity. Transfection enhancement is mediated by NS1's effector domain through
inhibition of IRF3 and PKR, activators of early anti-viral responses as well as
CPSF30, a non immunostimulating protein. Importantly, host gene inhibition
mediated via CPSF30 inhibition is a highly effective immune evasion mechanism
because it blocks de novo gene expression non-specifically and inhibits global
anti-viral responses during mRNA transfection. We show that only NS1 with CPSF30
inhibition property can enhance modified mRNA transfections. Furthermore,
transfection efficiency of unmodified mRNA, if co-delivered with NS1-TX91 mRNA,
can exceed that of modified mRNA in HepG2, RAW 264.7 and HeLa cells. The novel
impact of NS1-TX91 lays the foundation of a virus inspired immune evasion genes
co-delivery approach that can address problems arising from RNA immunogenicity
for non-vaccine mRNA therapeutics in an affordable and scalable way. It is also
transferable to applications that benefits from active inhibition of material
induced immunogenicity.
PMID- 28426974
TI - Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal
therapy.
AB - Two of the challenges for clinical implementation of nano-therapeutic strategies
are optimization of tumor targeting and clearance of the nanoagents in vivo.
Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within
macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near
infrared photothermal performance exhibit high macrophage uptake and negligible
cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages.
Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous
injection show prolonged blood circulation and can overcome the hypoxia
associated drug delivery barrier to target the tumor efficiently and dramatically
enhance the efficiency of photothermal cancer therapy. The Bi2Se3-laden
macrophages possess good biocompatibility as demonstrated by the biochemical and
histological analyses and furthermore, most of the materials are excreted from
the body within 25 days. Our findings reveal a desirable system for highly
efficient near-infrared photothermal cancer therapy.
PMID- 28426975
TI - The regulation of the chloroplast proton motive force plays a key role for
photosynthesis in fluctuating light.
AB - Plants use sunlight as their primary energy source. During photosynthesis,
absorbed light energy generates reducing power by driving electron transfer
reactions. These are coupled to the transfer of protons into the thylakoid lumen,
generating a proton motive force (pmf) required for ATP synthesis. Sudden
alterations in light availability have to be met by regulatory mechanisms to
avoid the over-accumulation of reactive intermediates and maximize energy
efficiency. Here, the acidification of the lumen, as an intermediate product of
photosynthesis, plays an important role by regulating photosynthesis in response
to excitation energy levels. Recent findings reveal pmf regulation and the
modulation of its composition as key determinants for efficient photosynthesis,
plant growth, and survival in fluctuating light environments.
PMID- 28426976
TI - Alternative electron transport pathways in photosynthesis: a confluence of
regulation.
AB - Photosynthetic reactions proceed along a linear electron transfer chain linking
water oxidation at photosystem II (PSII) to CO2 reduction in the Calvin-Benson
Bassham cycle. Alternative pathways poise the electron carriers along the chain
in response to changing light, temperature and CO2 inputs, under prolonged
hydration stress and during development. We describe recent literature that
reports the physiological functions of new molecular players. Such highlights
include the flavodiiron proteins and their important role in the green lineage.
The parsing of the proton-motive force between DeltapH and Deltapsi, regulated in
many different ways (cyclic electron flow, ATPsynthase conductivity, ion/H+
transporters), is comprehensively reported. This review focuses on an integrated
description of alternative electron transfer pathways and how they contribute to
photosynthetic productivity in the context of plant fitness to the environment.
PMID- 28426977
TI - Blue/violet laser inactivates methicillin-resistant Staphylococcus aureus by
altering its transmembrane potential.
AB - The resistance of methicillin-resistant Staphylococcus aureus to antibiotics
presents serious clinical problems that prompted the need for finding alternative
or combination therapies. One such therapy is irradiation with blue light. To
determine the alterations in metabolic processes implicated in the observed
antimicrobial effects of blue light, we investigated the changes in membrane
potential and the presence of free-radical-producing photo-acceptor molecules.
Bacterial cultures irradiated with one or two doses of 405nm laser light (each
consisting of 121J/cm2) were imaged with spectrally resolved laser-scanning
microscopes to detect endogenous fluorescent species as well as the voltage
sensitive dye 3,3'-Diethyloxacarbocyanine iodide. The endogenous fluorescence
indicated the presence of photosensitizers (i.e., porphyrins, NADH, FAD) in the
cells, while the exogenous signal allowed us to monitor rapid changes in
transmembrane potential following treatment with light. The changes were drastic
within the first 5min after irradiation with the first dose and continued slowly
after the second irradiation. These results suggest that the early antimicrobial
activity of blue light results from alteration of membrane integrity with a
consequent decrease in membrane polarization and rapid alteration of vital
cellular functions. The observation of an early antimicrobial activity of light
is very encouraging, as it suggests that treatment does not necessarily have to
be administered over a long period of time.
PMID- 28426978
TI - Visualizing spatial distribution of small molecules in the rhubarb stalk (Rheum
rhabarbarum) by surface-transfer mass spectrometry imaging.
AB - Laser desorption/ionization mass spectrometry imaging (LDI-MSI) with gold
nanoparticle-enhanced target (AuNPET) was used for visualization of small
molecules in the rhubarb stalk (Rheum rhabarbarum L.). Analysis was focused on
spatial distribution of biologically active compounds which are found in rhubarb
species. Detected compounds belong to a very wide range of chemical compound
classes such as anthraquinone derivatives and their glucosides, stilbenes,
anthocyanins, flavonoids, polyphenols, organic acids, chromenes, chromanones,
chromone glycosides and vitamins. The analysis of the spatial distribution of
these compounds in rhubarb stalk with the nanoparticle-rich surface of AuNPET
target plate has been made without additional matrix and with minimal sample
preparation steps.
PMID- 28426979
TI - Response-based sleep intervention: Helping infants sleep without making them cry.
PMID- 28426980
TI - Hormonal and reproductive risk factors of papillary thyroid cancer: A population
based case-control study in France.
AB - The three times higher incidence of thyroid cancer in women compared to men
points to a role of female sex hormones in its etiology. However the effects of
these factors are poorly understood. We analyzed the association between thyroid
cancer and hormonal and reproductive factors among women enrolled in CATHY, a
population-based case-control study conducted in France. The study included 430
cases of papillary thyroid cancer and 505 controls frequency-matched on age and
area of residence. The odds ratios for thyroid cancer increased with age at
menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared
to premenopausal women, particularly if menopause followed an ovariectomy, and
for women with age at menopause <55years. In addition, use of oral contraceptives
and menopausal hormone therapy reduced the association with thyroid cancer by
about one third, and breastfeeding by 27%. Overall, these findings provide
evidence that the risk of thyroid cancer increases with later age at menarche and
after menopause, and decreases with use of oral contraceptives and menopausal
hormone therapy. These findings confirm an implication of hormonal factors in
papillary thyroid cancer risk, whose mechanisms need to be elucidated.
PMID- 28426981
TI - Overall survival in elderly patients with colorectal cancer: A population-based
study in the Caribbean.
AB - BACKGROUND: Population-based Cancer registries (PBCR) play an important role in
cancer surveillance and research. The aim of this study was to examine overall
survival in elderly patients with colorectal cancer (CRC) by analysing data from
the Martinique PBCR between 1993 and 2012. METHODS: The log-rank test was used to
assess the statistical differences of the survival curves by each categorical
variable: age at diagnosis, sex, histology, zone of residence, subsite, stage at
diagnosis, and chemotherapy. A multivariable Cox model was performed to identify
independent prognostic factors for overall survival in elderly patients with
colorectal cancer. RESULTS: Among 2230 patients included in the study, 60.8% were
aged>=65years; mean age at diagnosis of these patients was 75.7+/-7.2years. For
the period 2008-2012, 532 elderly patients were analysed; mean age of those
receiving chemotherapy was 73.0+/-0.4 versus 77.9+/-0.4years for those not
receiving chemotherapy (p<0.0001). Stage at diagnosis was evaluated in 87.8%
(467/532) of patients; 63.0% (294/467) had stage III-IV and 49.3% of these
patients (145/294) received chemotherapy. Chemotherapy was less frequently
prescribed in patients aged 75-84 and >=85 years as compared to those aged 65-74
years (41.1% and 15.0% versus 64.6% respectively; p<0.0001). Stage III-IV at
diagnosis (HR=5.25; 3.70-7.45; p<0.0001), and not receiving chemotherapy
(HR=3.05; 2.23-4.16; p<0.0001), were independent prognostic factors for overall
survival. CONCLUSION: Our study highlights the role of PBCR in evaluating cancer
survival and patterns of care in elderly people of the French West- Indies.
Chemotherapy was less frequently prescribed among the elderly.
PMID- 28426983
TI - Constraining the temporal variations of Ra isotopes and Rn in the groundwater end
member: Implications for derived SGD estimates.
AB - Submarine groundwater discharge (SGD) has been recognized as an important
supplier of chemical compounds to the ocean that may influence coastal
geochemical cycles. Radium isotopes (223Ra, 224Ra, 226Ra,228Ra) and radon (222Rn)
have been widely applied as tracers of SGD. Their application requires the
appropriate characterization of both the concentrations of tracers in the
discharging groundwater and their distribution in the coastal water column. This
study evaluates the temporal evolution of Ra isotopes and 222Rn concentrations in
a dynamic subterranean estuary of a microtidal Mediterranean coastal aquifer that
experiences large displacements of the fresh-saltwater interface as a necessary
initial step in evaluating the influence of SGD in coastal waters. We show that
changes in groundwater salinities due to the seaward displacement of the fresh
saltwater interface produced large variations in Ra activities in groundwater (by
a factor of ~19, ~14, ~6, and ~11 for 223Ra, 224Ra, 226Ra and 228Ra,
respectively), most importantly during rainfall events. In contrast, the 222Rn
activities in groundwater oscillated only by a factor of 3 during these rainy
periods. The large temporal variability in Ra activities hampers the
characterization of the SGD end-member when using Ra isotopes as tracers, and
thus presents a challenge for obtaining accurate SGD estimates. This study
emphasizes the need to understand the hydrodynamics of coastal aquifers to
appropriately constrain the Ra isotopes and 222Rn concentrations in groundwater
and when applying both tracers in dynamic microtidal coastal systems.
PMID- 28426982
TI - Redox environment in stem and differentiated cells: A quantitative approach.
AB - Stem cells are believed to maintain a specific intracellular redox status through
a combination of enhanced removal capacity and limited production of ROS. In the
present study, we challenge this assumption by developing a quantitative approach
for the analysis of the pro- and antioxidant ability of human embryonic stem
cells in comparison with their differentiated descendants, as well as adult stem
and non-stem cells. Our measurements showed that embryonic stem cells are
characterized by low ROS level, low rate of extracellular hydrogen peroxide
removal and low threshold for peroxide-induced cytotoxicity. However, biochemical
normalization of these parameters to cell volume/protein leads to matching of
normalized values in stem and differentiated cells and shows that tested in the
present study cells (human embryonic stem cells and their fibroblast-like
progenies, adult mesenchymal stem cells, lymphocytes, HeLa) maintain similar
intracellular redox status. Based on these observations, we propose to use ROS
concentration averaged over the cell volume instead of ROS level as a measure of
intracellular redox balance. We show that attempts to use ROS level for
comparative analysis of redox status of morphologically different cells could
lead to false conclusions. Methods for the assessment of ROS concentration based
on flow cytometry analysis with the use of H2DCFDA dye and HyPer, genetically
encoded probe for hydrogen peroxide, are discussed.
PMID- 28426984
TI - Biomagnetic monitoring and element content of lichen transplants in a mixed land
use area of NE Italy.
AB - The aim of this study was to verify whether it is possible to discriminate
between the different pollution sources present in a mixed land use area of NE
Italy on the basis of the magnetic properties and the element content of lichen
transplants. Thalli of Pseudevernia furfuracea were collected in a pristine area
of the South-Eastern Alps and exposed for 2months in 40 sites located at the
knots of a 700m step grid covering ca. 40km2 of a mosaic of agricultural,
forested, industrial and urban areas. In this way, the samples could be analyzed
after a defined period of time, and compared to pre-exposure conditions. The post
exposure element content and the magnetic data substantially agreed, revealing a
rather modest anthropogenic impact on the territory, mostly limited to an
industrial park. Since the magnetic mineralogy was homogeneous throughout the
entire set of samples, with magnetite-like minerals as the main magnetic
carriers, it was not possible to discriminate between PM originating from the
different pollution sources. The contribution given by the industrial park could
be confirmed by the multivariate analysis of the element data set. Conversely, it
was possible to assess the low environmental impact of the largest local
industry, a cement plant, located outside the industrial park. Notwithstanding
the relatively short time of the survey, P. furfuracea was proven to be an
effective accumulator for biomagnetic monitoring studies, its magnetic properties
being excellent proxies for heavy metal pollution even when the anthropogenic
impact on the territory is low.
PMID- 28426985
TI - Current uses of ground penetrating radar in groundwater-dependent ecosystems
research.
AB - Ground penetrating radar (GPR) is a high-resolution technique widely used in
shallow groundwater prospecting. This makes GPR ideal to characterize the
hydrogeological functioning of groundwater-dependent ecosystems (GDE). This paper
reviews current uses of GPR in GDE research through the construction of a
database comprising 91 worldwide GPR case studies selected from the literature
and classified according to (1) geological environments favouring GDE; (2)
hydrogeological research interests; and (3) field technical and (4)
hydrogeological conditions of the survey. The database analysis showed that
inland alluvial, colluvial, and glacial formations were the most widely covered
geological environments. Water-table depth was the most repeated research
interest. By contrast, weathered-marl and crystalline-rock environments as well
as the delineation of salinity interfaces in coastal and inland areas were less
studied. Despite that shallow groundwater propitiated GDE in almost all the GPR
case studies compiled, only one case expressly addressed GDE research. Common
ranges of prospecting depth, water-table depth, and volumetric water content
deduced by GPR and other techniques were identified. Antenna frequency of 100MHz
and the common offset acquisition technique predominated in the database. Most of
GPR case studies were in 30-50 degrees N temperate latitudes, mainly in Europe
and North America. Eight original radargrams were selected from several GPR
profiles performed in 2014 and 2015 to document database classes and identified
gaps, as well as to define experimental ranges of operability in GDE
environments. The results contribute to the design of proper GPR surveys in GDE
research.
PMID- 28426986
TI - Schrodinger's code-script: not a genetic cipher but a code of development.
AB - In his book What is Life? Erwin Schrodinger coined the term 'code-script',
thought by some to be the first published suggestion of a hereditary code and
perhaps a forerunner of the genetic code. The etymology of 'code' suggests three
meanings relevant to 'code-script which we distinguish as 'cipher-code', 'word
code' and 'rule-code'. Cipher-codes and word-codes entail translation of one set
of characters into another. The genetic code comprises not one but two cipher
codes: the first is the DNA 'base-pairing cipher'; the second is the 'nucleotide
amino-acid cipher', which involves the translation of DNA base sequences into
amino-acid sequences. We suggest that Schrodinger's code-script is a form of
'rule-code', a set of rules that, like the 'highway code' or 'penal code',
requires no translation of a message. Schrodinger first relates his code-script
to chromosomal genes made of protein. Ignorant of its properties, however, he
later abandons 'protein' and adopts in its place a hypothetical, isomeric
'aperiodic solid' whose atoms he imagines rearranged in countless different
conformations, which together are responsible for the patterns of ontogenetic
development. In an attempt to explain the large number of combinations required,
Schrodinger referred to the Morse code (a cipher) but in doing so unwittingly
misled readers into believing that he intended a cipher-code resembling the
genetic code. We argue that the modern equivalent of Schrodinger's code-script is
a rule-code of organismal development based largely on the synthesis, folding,
properties and interactions of numerous proteins, each performing a specific
task.
PMID- 28426987
TI - A review on nitrous oxide (N2O) emissions during biological nutrient removal from
municipal wastewater and sludge reject water.
AB - Nitrous oxide (N2O) is an important pollutant which is emitted during the
biological nutrient removal (BNR) processes of wastewater treatment. Since it has
a greenhouse effect which is 265 times higher than carbon dioxide, even
relatively small amounts can result in a significant carbon footprint. Biological
nitrogen (N) removal conventionally occurs with nitrification/denitrification,
yet also through advanced processes such as nitritation/denitritation and
completely autotrophic N-removal. The microbial pathways leading to the N2O
emission include hydroxylamine oxidation and nitrifier denitrification, both
activated by ammonia oxidizing bacteria, and heterotrophic denitrification. In
this work, a critical review of the existing literature on N2O emissions during
BNR is presented focusing on the most contributing parameters. Various factors
increasing the N2O emissions either per se or combined are identified: low
dissolved oxygen, high nitrite accumulation, low chemical oxygen demand to
nitrogen ratio, slow growth of denitrifying bacteria, uncontrolled pH and
temperature. However, there is no common pattern in reporting the N2O generation
amongst the cited studies, a fact that complicates its evaluation. When
simulating N2O emissions, all microbial pathways along with the potential
contribution of abiotic N2O production during wastewater treatment at different
dissolved oxygen/nitrite levels should be considered. The undeniable validation
of the robustness of such models calls for reliable quantification techniques
which simultaneously describe dissolved and gaseous N2O dynamics. Thus, the
choice of the N-removal process, the optimal selection of operational parameters
and the establishment of validated dynamic models combining multiple N2O pathways
are essential for studying the emissions mitigation.
PMID- 28426988
TI - Solar photocatalytic application of NbO2OH as alternative photocatalyst for water
treatment.
AB - Water recycling and industrial effluents remediation are a hot topic of research
to reduce the environmental impact of the human activity. Persistent organic
pollutants are highly recalcitrant compounds with hazardous effects associated to
their fate in water bodies. Several novel technologies have been developed during
the last decades to deal with this novel contamination. However, the natural
sources and idiosyncrasy of each country lead to the potential application of
different technologies. In this context, we have focused on the development of
phocotalytic treatment of solutions containing dyes using a novel photocatalytic
material, the NbO2OH. The NbO2OH was synthesized and characterized with different
techniques. Several assays demonstrated the solar photoactivity of this novel
oxyhydroxide catalyst, achieving complete decolorizations after 10min of
treatment under optimal conditions of 1.0gL-1 NbO2OH photocatalyst loading, 0.1M
of H2O2 as electron scavenger, pH4.0 and methyl orange concentrations up to 15mgL
1. Also, the catalyst recuperation demonstrated the potential reuse of this
photocatalyst without losing catalytic response after five cycles. This work is
of significant importance because niobium is a natural resource, mainly extracted
in Brazil and the annual global sunlight irradiation in the near-equatorial
region of northeast Brazil is over the average solar irradiation of the planet.
Thus, the solar photocatalytic treatment using NbO2OH in northeast Brazil appears
as a highly potential environmental-friendly nanotechnology to mitigate the water
pollution.
PMID- 28426989
TI - The thermal impact of subsurface building structures on urban groundwater
resources - A paradigmatic example.
AB - Shallow subsurface thermal regimes in urban areas are increasingly impacted by
anthropogenic activities, which include infrastructure development like
underground traffic lines as well as industrial and residential subsurface
buildings. In combination with the progressive use of shallow geothermal energy
systems, this results in the so-called subsurface urban heat island effect. This
article emphasizes the importance of considering the thermal impact of subsurface
structures, which commonly is underestimated due to missing information and of
reliable subsurface temperature data. Based on synthetic heat-transport models
different settings of the urban environment were investigated, including: (1)
hydraulic gradients and conductivities, which result in different groundwater
flow velocities; (2) aquifer properties like groundwater thickness to aquitard
and depth to water table; and (3) constructional features, such as building
depths and thermal properties of building structures. Our results demonstrate
that with rising groundwater flow velocities, the heat-load from building
structures increase, whereas down-gradient groundwater temperatures decrease.
Thermal impacts on subsurface resources therefore have to be related to the
permeability of aquifers and hydraulic boundary conditions. In regard to the
urban settings of Basel, Switzerland, flow velocities of around 1 md-1 delineate
a marker where either down-gradient temperature deviations or heat-loads into the
subsurface are more relevant. Furthermore, no direct thermal influence on
groundwater resources should be expected for aquifers with groundwater
thicknesses larger 10m and when the distance of the building structure to the
groundwater table is higher than around 10m. We demonstrate that measuring
temperature changes down-gradient of subsurface structures is insufficient
overall to assess thermal impacts, particularly in urban areas. Moreover, in
areas which are densely urbanized, and where groundwater flow velocities are low,
appropriate measures for assessing thermal impacts should specifically include a
quantification of heat-loads into the subsurface which result in a more diffuse
thermal contamination of urban groundwater resources.
PMID- 28426990
TI - Concentration of perfluorinated compounds and cotinine in human foetal organs,
placenta, and maternal plasma.
AB - BACKGROUND: Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants,
and prenatal exposure to PFASs is believed to impact human foetal development and
may have long-term adverse health effects later in life. Additionally, maternal
cigarette smoking may be associated with PFAS levels. Foetal exposure has
previously been estimated from umbilical cord plasma, but the actual
concentration in foetal organs has never been measured. OBJECTIVES: The
concentrations of 5 PFASs and cotinine - the primary metabolite of nicotine -
were measured in human foetuses, placentas, and maternal plasma to evaluate to
what extent these compounds were transferred from mother to foetus and to
determine if the PFAS concentrations were associated with maternal cigarette
smoking. METHODS: Thirty-nine Danish women who underwent legal termination of
pregnancy before gestational week 12 were included; 24 maternal blood samples
were obtained together with 34 placental samples and 108 foetal organs. PFASs and
cotinine were assayed by liquid chromatography/triple quadrupole mass
spectrometry. RESULTS: In foetal organs, the average concentrations of
perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA),
perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDa), and
perfluorodecanoic acid (PFDA) were 0.6ng/g, 0.2ng/g, 0.1ng/g, 0.1ng/g, and
0.1ng/g, respectively. A significant positive correlation was found between the
exposure duration, defined as foetal age, and foetal to maternal ratio for all
five PFASs and cotinine. Smokers presented 99ng/g cotinine in plasma, 108ng/g in
placenta, and 61ng/g in foetal organs. No correlation between the maternal
cotinine concentrations and PFAS concentrations was found. CONCLUSIONS: PFASs
were transferred from mother to foetus, however, with different efficiencies. The
concentrations of PFOS, PFOA, PFNA, PFUnDA, and PFDA in foetal organs were much
lower than the maternal concentrations. Furthermore, a significant correlation
between the exposure duration and all of the evaluated PFASs was found. The
health-compromising concentrations of these substances during foetal development
are unknown.
PMID- 28426991
TI - Clinical usefulness of 18F-FDG PET/CT for initial staging and assessment of
treatment efficacy in patients with lymph node tuberculosis.
AB - INTRODUCTION: Few studies have evaluated the promising role of 18F-fluoro-2-deoxy
D-glucose positron emission tomography (PET) and PET/computed tomography FDG
PET/CT in evaluating and monitoring treatment response in patients with lymph
node tuberculosis (LNTB). The aim of this clinical investigation was to assess
the clinical usefulness of FDG PET/CT for initial tuberculosis staging and to
determine the prognostic value of the decrease of 18F-FDG uptake during
antibiotic treatment in LNTB patients. METHODS: We retrospectively reviewed 18
cases of LNTB admitted at a single center from 2004 to 2014. Medical records of
patients who underwent two FDG PET/CT (>6 months interval), at initial staging
and at the end of therapy were reviewed to determine the impact of FDG PET/CT on
initial management of LNTB and response to therapy. Statistical analysis was
performed using linear mixed-effects model. RESULTS: Thirteen cases of
disseminated LNTB and five cases of localized LNTB were included in the study.
Initial FDG PET/CT allowed guided biopsy for initial diagnosis in 5 patients and
identified unknown extra-LN TB sites in 9 patients. Visual analysis follow-up of
FDG PET/CT showed a complete metabolic response in 9/18 patients (all of whom
were cured), a partial response in 7/18 (5 of whom were cured) and no response in
2/18 (all of whom were not cured). The semi-quantitative evaluation of 18F-FDG
intensity decrease based on the maximum standardized uptake value (SUVmax),
compared to targeted estimated decrease allowed to predict correctly a complete
response to treatment in 14/18 cases. CONCLUSION: FDG PET/CT allows an accurate
pre-therapeutic mapping of LNTB and helps for early TB confirmation. The SUVmax
follow up is a potential tool for monitoring the treatment response.
PMID- 28426992
TI - Factors affecting sound energy absorbance in acute otitis media model of
chinchilla.
AB - Acute otitis media (AOM) is a rapid-onset infection of the middle ear which
results in middle ear pressure (MEP), middle ear effusion (MEE), and structural
changes in middle ear tissues. Previous studies from our laboratory have
identified that MEP, MEE, and middle ear structural changes are three factors
affecting tympanic membrane (TM) mobility and hearing levels (Guan et al., 2014,
2013). Sound energy reflectance or absorbance (EA) is a diagnostic tool
increasingly used in clinical settings for the identification of middle ear
diseases. However, it is unclear whether EA can differentiate these three factors
in an AOM ear. Here we report wideband EA measurements in the AOM model of
chinchilla at three experimental stages: unopened, pressure released, and
effusion removed. These correspond to the combined and individual effects of the
three factors on sound energy transmission. AOM was produced by transbullar
injection of Haemophilus influenzae in two treatment groups: 4 days (4D) and 8
days (8D) post inoculation. These time points represent the relatively early and
later phase of AOM. In each group of chinchillas, EA at 250-8000 Hz was measured
using a wideband tympanometer at three experimental stages. Results show that the
effects of MEP, MEE, and tissue structural changes over the frequency range
varied with the disease time course. MEP was the primary contributor to reduction
of EA in 4D AOM ears and had a smaller effect in 8D ears. MEE reduced the EA at 6
8 kHz in 4D ears and 2-8 kHz in 8D ears and was responsible for the EA peak in
both 4D and 8D ears. The residual EA loss due to structural changes was observed
over the frequency range in 8D ears and only at high frequencies in 4D ears. The
EA measurements were also compared with the published TM mobility loss in
chinchilla AOM ears.
PMID- 28426993
TI - A new combined method of stable isotope-labeling derivatization-ultrasound
assisted dispersive liquid-liquid microextraction for the determination of
neurotransmitters in rat brain microdialysates by ultra high performance liquid
chromatography tandem mass spectrometry.
AB - In this work, for the first time, a new hyphenated technique of stable isotope
labeling derivatization-ultrasound-assisted dispersive liquid-liquid
microextraction has been developed for the simultaneous determination of
monoamine neurotransmitters (MANTs) and their biosynthesis precursors and
metabolites. The developed method was based on ultra high performance liquid
chromatography tandem mass spectrometry detection using multiple-reaction
monitoring mode. A pair of mass spectrometry sensitizing reagents, d0-10-methyl
acridone-2-sulfonyl chloride and d3-10-methyl-acridone-2-sulfonyl chloride, as
stable isotope probes was utilized to facilely label neurotransmitters,
respectively. The heavy labeled MANTs standards were prepared and used as
internal standards for quantification to minimize the matrix effects in mass
spectrometry analysis. Low toxic bromobenzene (extractant) and acetonitrile
(dispersant) were utilized in microextraction procedure. Under the optimized
conditions, good linearity was observed with the limits of detection (S/N>3) and
limits of quantification (S/N>10) in the range of 0.002-0.010 and 0.015
0.040nmol/L, respectively. Meanwhile, it also brought acceptable precision (4.2
8.8%, peak area RSDs %) and accuracy (recovery, 96.9-104.1%) results. This method
was successfully applied to the simultaneous determination of monoamine
neurotransmitters and their biosynthesis precursors and metabolites in rat brain
microdialysates of Parkinson's disease and normal rats. This provided a new
method for the neurotransmitters related studies in the future.
PMID- 28426994
TI - Silica nanoparticles induced intrinsic apoptosis in neuroblastoma SH-SY5Y cells
via CytC/Apaf-1 pathway.
AB - The present study was to investigate effects of Silica nanoparticles (SiNPs) on
nervous system and explore potential mechanisms in human neuroblastoma cells (SH
SY5Y). Cytotoxicity was detected by cell viability and Lactate dehydrogenase
(LDH) release. Flow cytometry analysis was applied to assess mitochondrial
membrane potential (MMP) loss, intracellular Ca2+ and apoptosis. To clarify the
mechanism of SiNPs-induced apoptosis, intrinsic apoptosis-related proteins were
detected. Our results showed that SiNPs caused cytotoxicity, cell membrane damage
and Ca2+ increase in a dose-dependent manner in SH-SY5Y cells. Both the
mitochondrial membrane potential (MMP) loss and potential mitochondria damage
resulted in Cyt C release to the cytoplasm. The elevated Cyt C and Apaf1 further
triggered intrinsic apoptosis via executive molecular caspase-9 and caspase-3.
The present study confirmed that SiNPs induced intrinsic apoptosis in
neuroblastoma SH-SY5Y cells via CytC/Apaf-1 pathway and provided a better
understanding of the potential toxicity induced by SiNPs on human neurocyte.
PMID- 28426995
TI - Antibacterial activity of N-methylbenzofuro[3,2-b]quinoline and N
methylbenzoindolo[3,2-b]-quinoline derivatives and study of their mode of action.
AB - The emergence of multidrug-resistant bacteria causes an urgent need for new
generation of antibiotics, which may have a different mechanism of inhibition or
killing action from the existing. Targeting at the inhibition of bacterial cell
division via the control of FtsZ function is one of the effective and promising
approaches. Some natural extracts from plants such as sanguinarine and berberine
(analogs of pyridinium compounds) are known to alter FtsZ function. In this
study, a series of novel quaternary pyridinium compounds was constructed based on
the N-methylbenzofuro[3,2-b]quinoline and N-methylbenzoindolo[3,2-b]-quinoline
derivatives and their antibacterial activity against nine significant pathogens
was investigated using broth microdilution method. In the in vitro assay, the
compounds showed strong antibacterial activities against various testing strains,
which include some drug-resistant strains such as methicillin-resistant S. aureus
and vancomycin-resistant E. faecium. Our results of morphology change of B.
subtilis cells and molecular docking proved that the compounds functioned as an
effective inhibitor to suppress FtsZ polymerization and FtsZ GTPase activity and
thus the compound stops cell division and cause cell death through interacting
with C-terminal interdomain cleft of FtsZ.
PMID- 28426996
TI - Design, synthesis, SAR discussion, in vitro and in vivo evaluation of novel
selective EGFR modulator to inhibit L858R/T790M double mutants.
AB - Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of
5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline derivatives were designed and
synthesized with the purpose to overcome the drug resistance resulted from
T790M/L858R double mutations. The most potent compound 8 showed excellent enzyme
inhibitory activities and selectivity with sub nanomolar IC50 values for both the
single L858R and double T790M/L858R mutant EGFRs, and was more than 8-fold
selective for wild type EGFR. Compound 8 exhibited good microsomes stabilities
and pharmacokinetic properties and lower binding affinity to hERG ion channel
than AZD9291 and displayed strong antiproliferative activity against the H1975
non-small cell lung cancer (NSCLC) cells bearing T790M/L858R and in vivo
anticancer efficacy in a human NSCLC (H1975) xenograft mouse model.
PMID- 28426997
TI - Design and synthesis of neolamellarin a derivatives targeting heat shock protein
90.
AB - In this study, we designed and synthesized a novel family of neolamellarin A
derivatives that showed high inhibitory activity toward heat shock protein 90
(Hsp90), a kinase associated with cell proliferation. The 3,4
bis(catechol)pyrrole scaffold and the benzyl group with methoxy modification at N
position of pyrrole are essential to the Hsp90 inhibitory activity and
cytotoxicity of these compounds. Western blot analysis demonstrated that these
compounds induced dramatic depletion of the examined client proteins of Hsp90,
and accelerated cancer cell apoptosis. Docking simulations suggested that the
binding mode of 9p was similar to that of the VER49009, a potent inhibitor of
Hsp90. Further molecular dynamics simulation indicated that the hydrophobic
interactions as well as the hydrogen bonds contributed to the high affinity of 9p
to Hsp90.
PMID- 28426998
TI - Can nursing students' perceived teacher enthusiasm dampen their class-related
boredom during theoretical lessons? A cross-sectional study among Chinese nursing
students.
AB - BACKGROUND: Class-related boredom experienced by nursing students during
theoretical lessons may affect their health and learning outcomes. Perceived
teacher enthusiasm of nursing students may dampen their boredom, but little
empirical research has investigated their relationship. OBJECTIVES: The aim of
the current study is to investigate the dampening effects of nursing students'
perceived teacher enthusiasm on their class-related boredom during theoretical
lessons. The main theoretical framework is control-value theory of achievement
emotions. DESIGN: A cross-sectional survey was used. METHODS: 352 nursing
students during their theoretical lessons completed questionnaires on perceived
teacher enthusiasm, boredom proneness, perceived task difficulty and class
related boredom. Correlation and classic multiple hierarchical analysis results
supported the hypothesis about the relationships among variables. RESULTS: After
controlling the effects of demographic variables, boredom proneness and perceived
task difficulty, perceived teacher enthusiasm negatively predicted class-related
boredom significantly. CONCLUSION: Perceived teacher enthusiasm of nursing
students can predict their class-related boredom significantly.
PMID- 28426999
TI - Emotional intelligence and affective events in nurse education: A narrative
review.
AB - OBJECTIVE: To investigate the current state of knowledge about emotional
intelligence and affective events that arise during nursing students' clinical
placement experiences. DESIGN: Narrative literature review. DATA SOURCES: CINAHL,
MEDLINE, PsycINFO, Scopus, Web of Science, ERIC and APAIS-Health databases
published in English between 1990 and 2016. REVIEW METHODS: Data extraction from
and constant comparative analysis of ten (10) research articles. RESULTS: We
found four main themes: (1) emotional intelligence buffers stress; (2) emotional
intelligence reduces anxiety associated with end of life care; (3) emotional
intelligence promotes effective communication; and (4) emotional intelligence
improves nursing performance. CONCLUSIONS: The articles we analysed adopted a
variety of emotional intelligence models. Using the Ashkanasy and Daus "three
stream" taxonomy (Stream 1: ability models; 2: self-report; 3: mixed models), we
found that Stream 2 self-report measures were the most popular followed by Stream
3 mixed model measures. None of the studies we surveyed used the Stream 1
approach. Findings nonetheless indicated that emotional intelligence was
important in maintaining physical and psychological well-being. We concluded that
developing emotional intelligence should be a useful adjunct to improve academic
and clinical performance and to reduce the risk of emotional distress during
clinical placement experiences. We call for more consistency in the use of
emotional intelligence tests as a means to create an empirical evidence base in
the field of nurse education.
PMID- 28427000
TI - Psychological maltreatment, coping strategies, and mental health problems: A
brief and effective measure of psychological maltreatment in adolescents.
AB - Psychological maltreatment is an important social and public health problem and
associated with a wide range of short and long-term outcomes in childhood to
adulthood. Given the importance of investigating mitigating factors on its
effect, the purpose of the present study is to investigate the mediating effect
of active and avoidant coping strategies on the association between psychological
maltreatment and mental health- internalizing and externalizing- problems in
adolescents. Participants of the study consisted of 783 adolescents, ranging in
age from 14 to 18 years (M=15.57, SD=0.88), with 52.9% female and 47.1% male.
Several structural equation models were conducted to investigate the mediating
role of coping strategies on the effect of psychological maltreatment on
adolescents' internalizing and externalizing problems. Findings from mediation
analyses demonstrated the mediating effect of active and avoidant coping
strategies on the association between psychological maltreatment and mental
health problems. The outcomes support adolescents use more avoidant coping
strategies and fewer active coping strategies in the face of psychological
maltreatment experiences, and this affects their mental health. Taken together,
these results should contribute to the design of prevention and intervention
services in order to promote mental health.
PMID- 28427001
TI - Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a
blunt cardiac injury: A case report.
AB - INTRODUCTION: Traumatic blunt cardiac injuries have a high mortality rate, and
prompt diagnosis and treatment can be lifesaving in cardiac tamponade.
PRESENTATION OF CASE: A 62-year-old man was transferred to the emergency
department after a motor vehicle accident. He was hemodynamically unstable. A
focused assessment with sonography in trauma (FAST) showed pericardial fluid with
right ventricular collapse consistent with cardiac tamponade in the subxiphoid
view. He collapsed despite a subxiphoid pericardiotomy. Owing to the ongoing
hemodynamic instability, we performed a left anterolateral thoracotomy. Direct
incision of the pericardium showed blood and clots within the pericardial space,
indicating hemopericardium. The heart stroke and hemodynamic status recovered on
removing the clot. DISCUSSION: Although the physical findings of cardiac
tamponade are not always apparent in life-threatening acute cardiac tamponade
after blunt trauma, FAST is a reliable tool for diagnosing and following cardiac
tamponade. A median sternotomy is a standard approach for evaluating cardiac
injury in hemodynamically stable patients with or without cardiopulmonary bypass.
However, a left anterior thoracotomy was the fastest, simplest life-saving
procedure considering the need for open-chest cardiac massage given our patient's
life-threatening condition. CONCLUSION: A prompt diagnosis using FAST and
treatment can be lifesaving in traumatic acute cardiac tamponade. A
pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac
decompression in acute traumatic cardiac tamponade in cases of ineffective
drainage due to clot formation within the pericardial space.
PMID- 28427002
TI - Incidental posterior mediastinal paraganglioma: The safe approach to management,
case report.
AB - INTRODUCTION: Paragangliomas are neuroendocrine tumors arising from chromaffin
cells located in sympathetic paraganglia. Mediastinal paragangliomas are
extremely rare and can be classified as functional or non-functional according to
their ability for secreting catecholamines. Patients can be asymptomatic and the
diagnosis is usually incidental. Complete surgical resection remains the standard
of care for paragangliomas. PRESENTATION OF CASE: We present a 44-year-old woman
with a functional mediastinal paraganglioma incidentally found during the
perioperative imaging workup for a diagnosed breast carcinoma. Chest radiograph
and computed tomography (CT) showed a well-defined lesion in the posterior
mediastinum suspicious for an esophageal malignancy. Endoscopic and CT-guided
biopsies were performed confirming the diagnosis of a neuroendocrine tumor.
Laboratory studies showed elevated catecholamines and chromogranin A levels,
consistent with a paraganglioma. Appropriate pre-operative management was done
and successful surgical resection without catecholamine related complications was
achieved. DISCUSSION: The workup and treatment of incidentally discovered adrenal
and extra-adrenal lesions are controversial. Because of the absence of symptoms
and the wider differential diagnosis of extra-adrenal lesions, an attempt for
biopsying and surgically remove these lesions prior to biochemical testing is not
an uncommon scenario, although this could be potentially harmful. Surgeons should
have an index of suspicion for catecholamine-secreting tumors and hormonal levels
should be assessed prior to biopsy or surgical resection. CONCLUSION: Surgeons
should consider paragangliomas as a differential diagnosis for extra-adrenal
lesions. Biochemical testing with catecholamines and chromogranin A levels should
be performed prior to biopsy or surgical removal in order to avoid catastrophic
complications.
PMID- 28427003
TI - CE method for the in-process control of the synthesis of active substances
conjugated with gold nanoparticles.
AB - A fast capillary electrophoresis method was developed and validated for the in
process control (IPC) of the synthesis of active substances (APIs) with gold
nanoparticles (AuNPs). The capillary electrophoresis method was key to ensure
that the reaction step conducted in order to obtain AuNP and API conjugates will
produce the expected product without the presence of free APIs, which is a
critical parameter determining the quality of the synthetic material. Capillary
electrophoresis was performed using uncoated fused-silica capillaries with the
effective length of 40cm, 50MUm i.d. and the background electrolyte consisted of
20mM borate buffer (pH 8.5) with the application of hydrodynamic injection
50mbar/5s, voltage 20kV, temperature of the capillary cassette 25 degrees C and
UV detection at 261nm for GE, 541nm for AuNP-GE, 227nm for PE and 535nm for AuNP
PE. During validation the specificity, linearity, accuracy, precision, range, and
stability of the sample solution were confirmed. The linear regression (R2=0.999)
between the corrected peak areas of the analytes and their amount was fulfilled
in the range from 2.4MUg/mL to 0.3mg/mL for genistein and from 4.6MUg/mL to
0.6mg/mL for pemetrexed. Within this range the method was proved to be accurate
(99.0% for genistein and 99.9% for pemetrexed) and precise for both analytes with
the intra-day RSD values of 0.77% and 0.97% for the migration time of genistein
and pemetrexed, respectively. The inter-day RSD values were 1.90% and 2.27% for
the migration time of genistein and pemetrexed, respectively. The LOD and LOQ
values for pemetrexed were 1.4MUg/mL and 4.6MUg/mL, respectively, and for
genistein 0.72MUg/mL and 2.4MUg/mL, respectively. The results obtained during the
validation indicate that the method is sufficient to be applied for the IPC of
the synthesis of APIs with gold nanoparticles.
PMID- 28427004
TI - Enzymatic activity of the CaM-PDE1 system upon addition of actinyl ions.
AB - The threat of a dirty bomb which could cause internal contamination has been of
major concern for the past decades. Because of their high chemical toxicity and
their presence in the nuclear fuel cycle, uranium and neptunium are two actinides
of high interest. Calmodulin (CaM) which is a ubiquitous protein present in all
eukaryotic cells and is involved in calcium-dependent signaling pathways has a
known affinity for uranyl and neptunyl ions. The impact of the complexation of
these actinides on the physiological response of the protein remains, however,
largely unknown. An isothermal titration calorimetry (ITC) was developed to
monitor in vitro the enzymatic activity of the phosphodiesterase enzyme which is
known to be activated by CaM and calcium. This approach showed that addition of
actinyl ions (AnO2n+), uranyl (UO22+) and neptunyl (NpO2+), resulted in a
decrease of the enzymatic activity, due to the formation of CaM-actinide
complexes, which inhibit the enzyme and alter its interaction with the substrate
by direct interaction. Results from dynamic light scattering rationalized this
result by showing that the CaM-actinyl complexes adopted a specific conformation
different from that of the CaM-Ca2+ complex. The effect of actinides could be
reversed using a hydroxypyridonate actinide decorporation agent (5-LIO(Me-3,2
HOPO)) in the experimental medium demonstrating its capacity to efficiently bind
the actinides and restore the calcium-dependent enzyme activation.
PMID- 28427005
TI - Diagnostic accuracy of magnetic resonance imaging in patients with suspected
pulmonary embolism: A bivariate meta-analysis.
AB - BACKGROUND: Computed tomographic pulmonary angiography (CTPA) has simplified the
diagnostic approach to patients with clinically suspected pulmonary embolism
(PE), but alternative imaging tests are still advocated. We aimed to
systematically assess the diagnostic accuracy of magnetic resonance imaging (MRI)
for PE diagnosis. METHODS: Studies evaluating the diagnostic accuracy of MRI for
the diagnosis of PE were systematically searched in the PubMed and EMBASE
databases (up to May 2016). QUADAS - 2 tool was used for the quality assessment
of the primary studies. A bivariate random-effects regression approach was used
for summary estimates of both sensitivity and specificity. RESULTS: Thirteen
studies, for a total of 1170 patients, were included. Weighted mean prevalence of
PE was 37% at random-effect model. Weighted mean inconclusive MRI results were
19% at random-effect model. After exclusion of technical inadequate results, MRI
bivariate weighted mean sensitivity was 80.9% (95% confidence interval [CI] 68.2,
89.4%), with a bivariate weighted mean specificity of 96.4% (95% CI 92.4, 98.3%),
CONCLUSIONS: MRI has high specificity but limited sensitivity for the diagnosis
of PE. Inconclusive results are a major limitation to the practical application
of MRI. Management studies are needed to more precisely define the role of MRI in
the diagnostic workup of patients with suspected PE.
PMID- 28427006
TI - Regeneration of pilot-scale ion exchange columns for hexavalent chromium removal.
AB - Due to stricter regulations, some drinking water utilities must implement
additional treatment processes to meet potable water standards for hexavalent
chromium (Cr(VI)), such as the California limit of 10 MUg/L. Strong base anion
exchange is effective for Cr(VI) removal, but efficient resin regeneration and
waste minimization are important for operational, economic and environmental
considerations. This study compared multiple regeneration methods on pilot-scale
columns on the basis of regeneration efficiency, waste production and salt usage.
A conventional 1-Stage regeneration using 2 N sodium chloride (NaCl) was compared
to 1) a 2-Stage process with 0.2 N NaCl followed by 2 N NaCl and 2) a mixed
regenerant solution with 2 N NaCl and 0.2 N sodium bicarbonate. All methods
eluted similar cumulative amounts of chromium with 2 N NaCl. The 2-Stage process
eluted an additional 20-30% of chromium in the 0.2 N fraction, but total resin
capacity is unaffected if this fraction is recycled to the ion exchange
headworks. The 2-Stage approach selectively eluted bicarbonate and sulfate with
0.2 N NaCl before regeneration using 2 N NaCl. Regeneration approach impacted the
elution efficiency of both uranium and vanadium. Regeneration without co-eluting
sulfate and bicarbonate led to incomplete uranium elution and potential formation
of insoluble uranium hydroxides that could lead to long-term resin fouling,
decreased capacity and render the resin a low-level radioactive solid waste.
Partial vanadium elution occurred during regeneration due to co-eluting sulfate
suppressing vanadium release. Waste production and salt usage were comparable for
the 1- and 2-Stage regeneration processes with similar operational setpoints with
respect to chromium or nitrate elution.
PMID- 28427007
TI - Novel and revisited approaches in antituberculosis drug discovery.
AB - The increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (Mtb)
necessitates the discovery and development of novel drugs against tuberculosis.
In this review, we focus on two recent approaches that led to the discovery of
promising antitubercular compound classes: (I) Hits derived from large compound
library screens are increasingly difficult to translate into clinical
application; this in turn fostered the development of innovative screening
methods. (II) An alternative strategy towards high-quality hits and leads is to
evaluate chemically diverse scaffolds which can be found among natural products.
The so-called rekindling and repurposing approaches were particularly fruitful in
the last few years.
PMID- 28427008
TI - Lateral hypothalamic circuits for sleep-wake control.
AB - The lateral hypothalamic area (LHA) of the diencephalon is crucially involved in
controlling instinctive behavior such as sleep-wake cycle and feeding behavior.
LHA is a heterogeneous structure that contains spatially intermingled,
genetically distinct cell populations. Among LHA neurons, orexin/hypocretin (OX)
neuron is the key cell type that promotes waking, and specific loss of OX neurons
results in narcolepsy. Melanin-concentrating hormone (MCH) containing neurons are
known to be active during rapid eye movement (REM) sleep and stimulation of these
neurons promotes REM sleep. Here we review the classical and more recent findings
in this field and discuss the molecular and cellular network organization of LHA
neurons that could ultimately regulate the switch between wakefulness and general
states of sleep.
PMID- 28427009
TI - Early-in-life dietary zinc deficiency and supplementation and mammary tumor
development in adulthood female rats.
AB - Zinc deficiency during pregnancy and postnatal life can adversely increase risk
of developing human diseases at adulthood. The present study was designed to
evaluate whether dietary zinc deficiency or supplementation during the pregnancy,
lactation and juvenile stages interferes in the development of mammary tumors
induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats.
Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA
- 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented
diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters'
weaning. Female offspring received the same diets as their dams until postnatal
day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg,
ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor
samples were processed for histological evaluation and gene expression microarray
analysis. The ZnD induced a significant reduction in female offspring body weight
evolution and in mammary gland development. At late in life, the ZnD or ZnS did
not alter the latency, incidence, multiplicity, volume or histological types of
mammary tumors in relation to the ZnA group. However, the total tumor number in
ZnS group was higher than in ZnA group, accompanied by distinct expression of 4
genes up- and 15 genes down-regulated. The present findings indicate that early
in-life dietary zinc supplementation, differently to zinc deficiency, has a
potential to modify the susceptibility to the development of mammary tumors
induced by DMBA.
PMID- 28427011
TI - Biosensors for the monitoring of harmful algal blooms.
AB - Harmful algal blooms (HABs) are a major global concern due to their propensity to
cause environmental damage, healthcare issues and economic losses. In particular,
the presence of toxic phytoplankton is a cause for concern. Current HAB
monitoring programs often involve laborious laboratory-based analysis at a high
cost and with long turnaround times. The latter also hampers the potential to
develop accurate and reliable models that can predict HAB occurrence. However, a
promising solution for this issue may be in the form of remotely deployed
biosensors, which can rapidly and continuously measure algal and toxin levels at
the point-of-need (PON), at a low cost. This review summarises the issues HABs
present, how they are difficult to monitor and recently developed biosensors that
may improve HAB-monitoring challenges.
PMID- 28427010
TI - Leveraging microbial biosynthetic pathways for the generation of 'drop-in'
biofuels.
AB - Advances in retooling microorganisms have enabled bioproduction of 'drop-in'
biofuels, fuels that are compatible with existing spark-ignition, compression
ignition, and gas-turbine engines. As the majority of petroleum consumption in
the United States consists of gasoline (47%), diesel fuel and heating oil (21%),
and jet fuel (8%), 'drop-in' biofuels that replace these petrochemical sources
are particularly attractive. In this review, we discuss the application of
aldehyde decarbonylases to produce gasoline substitutes from fatty acid products,
a recently crystallized reductase that could hydrogenate jet fuel precursors from
terpene synthases, and the exquisite control of polyketide synthases to produce
biofuels with desired physical properties (e.g., lower freezing points). With our
increased understanding of biosynthetic logic of metabolic pathways, we discuss
the unique advantages of fatty acid, terpene, and polyketide synthases for the
production of bio-based gasoline, diesel and jet fuel.
PMID- 28427012
TI - Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc
glycosylation.
AB - O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role
in modulating protein function in many cellular processes and human diseases such
as Alzheimer's disease and type II diabetes, and has emerged as a promising new
target. Specific inhibitors of OGT could be valuable tools to probe the
biological functions of O-GlcNAcylation, but a lack of robust nonradiometric
assay strategies to detect glycosylation, has impeded efforts to identify such
compounds. Here we have developed a novel label-free electrochemical biosensor
for the detection of peptide O-GlcNAcylation using protease-protection strategy
and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a
signal reporter. There is a large difference in the abilities of proteolysis of
the glycosylated and the unglycosylated peptides by protease, thus providing a
sensing mechanism for OGT activity. When the O-GlcNAcylation is achieved, the
glycosylated peptides cannot be cleaved by proteinase K and result in a high
current response on indium tin oxide (ITO) electrode. However, when the O
GlcNAcylation is successfully inhibited using a small molecule, the
unglycosylated peptides can be cleaved easily and lead to low current signal.
Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined
small-molecule OGT inhibitor. The results indicated that the biosensor could be
used to screen the OGT inhibitors effectively. Our label-free electrochemical
method is a promising candidate for protein glycosylation pathway research in
screening small-molecule inhibitors of OGT.
PMID- 28427013
TI - The accelerated path of ceritinib: Translating pre-clinical development into
clinical efficacy.
AB - The discovery of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung
cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK
inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance
to crizotinib invariably develops. There is now a next generation of ALK
inhibitors, including two that have been approved-ceritinib and alectinib-and
others that are in development-brigatinib, lorlatinib and X-396. Ceritinib and
the other next-generation ALK inhibitors are more potent than crizotinib and can
overcome tumor cell resistance mechanisms. Ceritinib gained US Food and Drug
Administration approval in 2014 following accelerated review for the treatment of
patients with ALK-positive (ALK+) metastatic NSCLC who have progressed on or are
intolerant to crizotinib. In pre-clinical studies, it demonstrated more potent
inhibition of ALK than crizotinib in enzymatic assays, more durable responses in
xenograft models and the ability to potently overcome crizotinib resistance
mutations in vitro (including the gatekeeper mutation). There is also evidence
for ceritinib penetration across the blood-brain barrier. In clinical trials,
ceritinib has demonstrated durable responses and progression-free survival in ALK
inhibitor-pre-treated and -naive NSCLC patients, including high overall and
intracranial response rates in those with central nervous system metastases.
Selective gastrointestinal toxicity of ceritinib, such as diarrhea, nausea and
vomiting is generally manageable with prophylactic medication and prompt dose
reduction or interruption. Future progress in treating ALK+ NSCLC will focus on
determining the optimal sequencing of therapies and strategies to overcome
acquired resistance, an ongoing challenge in treating ALK-mutation-driven tumors.
PMID- 28427014
TI - Chemical and biological properties of a supramolecular complex of tuftsin and
cucurbit[7]uril.
AB - Cucurbit[7]uril (CB7) is an uncharged and water-soluble macrocyclic host. CB7
binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg,
with moderate affinity (Ka=2.1*103M-1). In this study, the host-guest
complexation was confirmed by fluorescence titration. This affinity would allow
for easy release of the peptide under physiological conditions. According to
density functional theory calculations, the structural binding motif involves
hydrogen bonding. The most energetically stable form had the Arg side chain
inside the CB7 cavity. The effects of the tuftsin-CB7 complex on the
proliferation and cytokine activity of immune cells were studied. The complex had
broader spectrum immunomodulation than free peptides, and caused statistically
significant (p<0,05) changes in cytokine production (tumor necrosis factor-alpha,
interleukin-2, interferon-gamma, and interleukin-10) by mononuclear cells. By
contrast, the free peptide only activated tumor necrosis factor-alpha production.
PMID- 28427015
TI - Apparent anisotropy of adhesive bonds with weak adhesion and non-destructive
evaluation of interfacial properties.
AB - The present research attempts to non-destructively characterize mechanical
properties, which are representative of the interfacial adhesion and bond line
cohesion of adhesively bonded assemblies, using an ultrasonic method. Eight
bonded samples made of two aluminium substrates and of an epoxy-based adhesive
layer were manufactured: four in which the adhesive is fully cured (100%) and
four in which crosslinking is partial (80%). For each level of curing, four
different surface treatments were applied to the aluminium substrates before
assembling, in order to vary the quality of adhesion. Ultrasonic plane wave
transmission coefficients (UPWTC) were either measured in a water tank, or
simulated using the well-known stiffness matrix method that micmics the
experiments, to produce input data for the inverse problem. This latest consists
in the evaluation of the elastic properties of either the adhesive bond or the
interphases between both substrates and the adhesive layer. If the interphases
are of nominal quality, the values of the inferred properties of the adhesive
bond match those previously measured on individual epoxy samples, whether the
epoxy is fully or partially cured. However, when interphases are not of nominal
quality level, the optimized bond moduli reveal an apparent anisotropy, although
the epoxy layer is known to be isotropic. This apparent anisotropy is explained
by an analytical rule of mixture, thus giving confidence in the proposed
ultrasonic technique, which is then suggested as a potential way to detect
weaknesses of interphases. Finally, the optimization of the interphases elastic
properties is carried out. The measured normal and shear stiffnesses are shown to
decrease as the interphases get degraded. All ultrasonically-measured parameters
(apparent anisotropy of the bond and interfacial stiffnesses) vary monotonically
with the bonds strength, which was measured via mechanical tests. The proposed
UPWTC method was shown to have a strong potential to distinguish between adhesive
and cohesive weaknesses of bonded joints, and to estimate corresponding
mechanical properties.
PMID- 28427016
TI - Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers
and novel cinnamic ester derivatives.
AB - Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi
crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been
synthesized starting from d-glucose. The key step of the synthesis is a new one
pot sequence that commenced with a Z-selective Wittig olefination of suitably
functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)
triphenylphosphorane, in dry methanol, to afford 1 or 3, in the mixtures with the
corresponding 4-epimers (2 or 4, respectively). A number of 6-O-cinnamoyl
derivatives of styryl lactones 1-4 have been prepared, bearing electron donating
or electron withdrawing functionalities in the C-4 position of cinnamic acid
residue. The synthesized products were evaluated for their in vitro
antiproliferative activity against selected human tumour cell lines, whereupon
very potent cytotoxicities have been recorded in many cases. SAR analysis
indicated some important structural features responsible for biological activity,
such as stereochemistry at the C-4 and C-7 positions, as well as the nature of a
substituent at the C-4 position in the aromatic ring of cinnamoate moiety. Flow
cytometry and Western blot analysis data gave insight in the mechanism underlying
antiproliferative effects of the synthesized compounds.
PMID- 28427017
TI - Aromatase inhibitors and apoptotic inducers: Design, synthesis, anticancer
activity and molecular modeling studies of novel phenothiazine derivatives
carrying sulfonamide moiety as hybrid molecules.
AB - Hybrid molecules are used as anticancer agents to improve effectiveness and
diminish drug resistance. So, the current study aimed to introduce twenty novel
phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer
activity. Compounds 11 and 13 revealed more potent anticancer properties (IC50
8.1 and 8.8 MUM) than that of the reference drug (doxorubicin, IC50 = 9.8 MUM)
against human breast cancer cell line (T47D). To determine the mechanism of their
anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed
promising activity on T47D, were evaluated for their aromatase inhibitory effect.
The study results disclose that the most potent aromatase inhibitors 11 and 13
showed the lowest IC50 (5.67 MUM and 6.7 MUM), respectively on the target enzyme.
Accordingly, the apoptotic effect of the most potent compound 11 was extensively
investigated and showed a marked increase in Bax level up to 55,000 folds, and
down-regulation in Bcl2 to 5.24*10-4 folds, in comparison to the control.
Furthermore, the effect of compound 11 on caspases 3, 8 and 9 was evaluated and
was found to increase their levels by 20, 34, and 8.9 folds, respectively, which
indicates the activation of both intrinsic and extrinsic pathways. Also, the
effect of compound 11 on the cell cycle and its cytotoxic effect were examined.
Moreover, a molecular docking and computer aided ADMET studies were adopted to
confirm their mechanism of action.
PMID- 28427018
TI - Left or right? Lateralizing temporal lobe epilepsy by dynamic amygdala fMRI.
AB - OBJECTIVES: In this case series, the findings of 85 functional MRI studies
employing a dynamic fearful face paradigm are reported. Previous findings have
shown the paradigm to generate bilateral amygdala activations in healthy subjects
and unilateral activations in patients with MTLE, in the contralateral hemisphere
to seizure origin. Such findings suggest ipsilateral limbic pathology and offer
collateral evidence in lateralizing MTLE. METHODS: The series includes 60
patients with TLE, 12 patients with extra-temporal lobe epilepsy, and 13 healthy
controls. Functional MRI studies using a 1.5T scanner were conducted over a three
year period at a single epilepsy center and individual results were compared with
EEG findings. RESULTS: In the cohort of unilateral TLE patients, lateralized
activations of the amygdala were concordant with EEG findings in 76% of patients
(77% lTLE, 74% rTLE). The differences in the mean lateralized indices of the
lTLE, rTLE, and healthy control groups were all statistically significant.
Lateralized amygdala activations were concordant with EEG findings in only 31% of
the 12 patients with extra-temporal lobe epilepsy and bilateral amygdala
activations were generated in all but one of the healthy control subjects.
SIGNIFICANCE: This case series further endorses the utility of the dynamic
fearful face functional MRI paradigm using the widely available 1.5T as an
adjunctive investigation to lateralize TLE.
PMID- 28427019
TI - Transplantation of inhibitory precursor cells from medial ganglionic eminence
produces distinct responses in two different models of acute seizure induction.
AB - Medial ganglionic eminence (MGE) is one of the sources of inhibitory interneurons
during development. Following transplantation in postnatal developing brain, MGE
cells can increase local inhibition suggesting a possible protection to GABAergic
dysfunction in brain disorders, such as epilepsy. Since it has been shown that
MGE-derived cells harvested as neurospheres are able to suppress seizures, it
might be important to investigate whether these protective effects would change
in different seizure models. Here, we used pentylenetetrazole-(PTZ) and maximal
electroshock (MES)-induced seizure models to test whether the transplantation of
MGE cells would increase the threshold to trigger acute seizures. When
transplanted into the neocortex (layers 3-4) of neonatal mice (postnatal days 3
4), MGE cells were able to survive and were mainly found in piriform cortex,
fimbria, and ventricular wall regions. Additionally, the number of GFP+ cells
found in the brains of mice induced with PTZ and MES differed significantly and
suggests proliferation and larger survival rate of MGE-transplanted cells after
PTZ, but not MES-induced seizures. Following transplantation, there was a
reduction in the number of animals presenting mild and severe seizures induced by
PTZ. Furthermore, MGE-cell transplantation was able to increase threshold to
seizures induced by PTZ, but was not able to prevent seizure spread induced by
MES.
PMID- 28427020
TI - Experiences with premorbid SUDEP discussion among participants in the North
American SUDEP Registry (NASR).
AB - The North American SUDEP Registry (NASR) is a repository of clinical data and
biospecimens in cases of sudden unexpected death in epilepsy (SUDEP), a leading
cause of epilepsy-related deaths. We assessed whether bereaved families were
aware of SUDEP before their family member's death and their preferences for SUDEP
disclosure. At enrollment, next-of-kin of SUDEP cases completed an intake
interview, including questions assessing premorbid SUDEP discussions. Only 18.1%
of the 138 next-of-kin recalled a previous discussion of SUDEP with a healthcare
provider or support resource. Of the 112 who did not recall such a discussion,
72.3% wished it was discussed, 10.7% were satisfied it was not discussed, and 17%
were unsure. A history of status epilepticus predicted SUDEP discussion. Rates of
SUDEP discussion were not significantly higher among SUDEPs after 2013 (the
approximate study midpoint) compared with those before then. Our study suggests
that SUDEP remains infrequently discussed with family members of persons with
epilepsy. Nearly three-quarters of family members wished they had known of SUDEP
before the death. However, some were indifferent or were satisfied that this
discussion had not occurred. We must balance more systematic education of
patients and families about SUDEP while respecting individual preferences about
having this discussion.
PMID- 28427021
TI - Risk factors for learning problems in youth with psychogenic non-epileptic
seizures.
AB - OBJECTIVES: This study examined the risk factors for learning problems (LP) in
pediatric psychogenic non-epileptic seizures (PNES) and their specificity by
comparing psychopathology, medical, cognitive/linguistic/achievement, bullying
history, and parent education variables between subjects with PNES with and
without LP and between subjects with PNES and siblings with LP. METHODS: 55
subjects with PNES and 35 siblings, aged 8-18years, underwent cognitive,
linguistic, and achievement testing, and completed somatization and anxiety
sensitivity questionnaires. A semi-structured psychiatric interview about the
child was administered to each subject and parent. Child self-report and/or
parent report provided information on the presence/absence of LP. Parents also
provided each subject's medical, psychiatric, family, and bullying history
information. RESULTS: Sixty percent (33/55) of the PNES and 49% (17/35) of the
sibling subjects had LP. A multivariable logistic regression demonstrated that
bullying and impaired formulation of a sentence using a stimulus picture and
stimulus word were significantly associated with increased likelihood of LP in
the PNES youth. In terms of the specificity of the LP risk factors, a similar
analysis comparing LP in the youth with PNES and sibling groups identified
anxiety disorder diagnoses and bullying as the significant risk factors
associated with LP in the PNES youth. CONCLUSIONS: These findings emphasize the
need to assess youth with PNES for LP, particularly if they have experienced
bullying, have linguistic deficits, and meet criteria for anxiety disorder
diagnoses.
PMID- 28427022
TI - Stereotypy of psychogenic nonepileptic seizures.
AB - Psychogenic nonepileptic seizures (PNES) are defined as paroxysmal episodes in
which epileptic semiology features are manifested, without the characteristic
concomitant electrical discharges seen in epileptic seizures. Although many
studies have dealt with semiologic classification of PNES, most of the studies
did not raise the question of consistency of PNES in the same patient. The aim of
this study was to measure the degree of consistency of PNES among individual
patients. We retrospectively reviewed medical records and video- EEG records of
all adult patients who underwent monitoring in our center from August 1st 2013 to
May 31st 2015. Those who were diagnosed with PNES with or without a background of
epilepsy were selected for this study. In order to check consistency between
seizures, we analyzed patients who had more than one recorded seizure during
monitoring. In case of more than 2 recorded seizures, the first two seizures were
analyzed. We found 53 patients who had PNES during this period, 29 of them had
more than one seizure. All seizures in the same patient were in the same
semiology category. In patients with either motor rhythmic or complex motor
seizures, we found a main anatomical region involved. The main anatomical region
involved was the same in 13 out of 14 patients. Movement frequency was highly
similar between the seizures of the same patient, while duration of seizures was
significantly different. Despite significant differences in duration between the
first and second seizure in patients with PNES, all other aspects tested were
highly similar. This shows that recurrent PNES in the same patient are
stereotypic. This supports the hypothesis that PNES is probably a dissociative
disorder.
PMID- 28427023
TI - The relationship between the Neuro-Quality of Life Depression and Anxiety
Measures and the Personality Assessment Inventory in persons with epilepsy.
AB - BACKGROUND: To investigate the associations between the Neuro-Quality of Life
(NQOL) Depression and Anxiety measures with an objective emotional inventory
(Personality Assessment Inventory; PAI), and demonstrate the clinical utility of
the NQOL as screening measures for depression and anxiety in persons with
epilepsy (PWE). METHODS: PWE (N=72) were concurrently administered the NQOL
Depression and Anxiety measures and the PAI. Pearson product moment correlations
were used to determine the relationships between the NQOL measures and the
respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted
comparing NQOL scores between patients with elevated levels of depression and
anxiety (T-score>=65 on the PAI) to profiles that were within normal limits.
Using sensitivity and specificity analyses, optimal cut-scores on the NQOL
measures were determined. RESULTS: Participants were primarily Caucasian (89%),
female (60%), and ~35 years old. The NQOL Depression measure was significantly
correlated with the PAI Depression total score (r=.747; p<0.001) and its
subscales (p's<0.001). Similarly, the NQOL Anxiety measure was significantly
correlated with the PAI Anxiety total score (r=.750; p<0.001) and its subscales
(p's<0.001). Compared to profiles that were within normal limits, individuals
with elevated depressive symptoms on the PAI had significantly higher NQOL
Depression scores (F(1,71)=48.2, p<0.001, d=1.6). Similarly, those who endorsed
elevated anxiety on the PAI had significantly higher NQOL Anxiety scores
(F(1,71)=32.2, p<0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and
24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67;
specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77;
specificity=0.82; PPV=0.81; NPV=0.78) in PWE. CONCLUSIONS: The NQOL Depression
and Anxiety measures evidenced strong associations with the PAI Depression and
Anxiety scales and may be effective in detecting depressive and anxiety symptoms
in PWE using the provided cut-scores.
PMID- 28427024
TI - Knowledge, attitude, and practice about epilepsy among teachers at Ethio-National
School, Addis Ababa, Ethiopia.
AB - BACKGROUND: Epilepsy is one of the most common serious chronic brain disorders
and is poorly understood by the public and has been associated with numerous
misconceptions and beliefs. This, coupled with its dramatic clinical
manifestations, has resulted in a strong social stigma. Since teachers have a key
role in society as educators, the purpose of this study was to find out the
knowledge, attitude, and practice towards epilepsy among school teachers.
METHODS: A cross-sectional study design was used to assess the knowledge,
attitude, and practice of 135 teachers about epilepsy using a semi-structured,
self-administered questionnaire. Data were entered into IBM SPSS version 20.0 and
analyzed. Descriptive statistics including frequencies, means, and standard
deviations were used to describe the data. Associations were computed using a chi
square test and p-value<0.05 was considered significant. RESULTS: Nearly all
teachers 122 (96.3 %) were aware of epilepsy. Only 41% of the respondents had
good knowledge about epilepsy whereas 26.8% and 32.3% had fair and poor knowledge
about the disease, respectively. About 74% of them had a positive attitude about
epilepsy. Only 60.3% of the respondents had proper first aid training. Literacy
status and years of experience were not significantly associated with the level
of knowledge about epilepsy. CONCLUSION: A significant proportion of teachers had
deficits in terms of general knowledge, attitude, and the appropriate management
of epilepsy in the classroom. Therefore, it is important to train and update
teachers on epilepsy by the responsible health authorities.
PMID- 28427025
TI - Psychiatric symptoms after temporal epilepsy surgery. A one-year follow-up study.
AB - Psychiatric symptoms must be considered in patients with refractory temporal lobe
epilepsy after epilepsy surgery. The main objectives of our study were to
describe clinical and socio-demographical characteristics of a cohort of patients
with pharmacoresistant temporal lobe epilepsy who underwent temporal lobe
epilepsy surgery, and moreover, to evaluate possible risk factors for developing
psychiatric symptoms. In order to achieve those goals, we conducted a prospective
evaluation of psychopathology throughout the first year after surgery in a
clinical sample of 72 patients, by means of three clinical rated measures; the
Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale
(HDRS), and the Brief Psychiatric Rating Scale (BPRS). The psychopathological
evaluations were performed by an experienced psychiatrist. A presurgical
evaluation was done by a multidisciplinary team (that includes neurologist,
psychiatrist, neurosurgeon, neurophysiologist, radiologists, and nuclear medicine
specialist) in all patients. The decision to proceed to surgery was taken after a
surgical meeting of all members of the Multidisciplinary Epilepsy Unit team. The
psychiatrist conducted two postoperative assessments at 6months and 12months
after surgery. The main finding was that past history of mental illness (patients
who were receiving psychiatric treatment prior to the baseline evaluation) was a
risk factor for anxiety, depression, and psychosis after temporal lobe epilepsy
surgery.
PMID- 28427026
TI - Epilepsy and headaches: Further evidence of a link.
AB - OBJECTIVE: Epilepsy and primary headaches are two of the most common neurologic
conditions that share some common clinical characteristics, and can affect
individuals of all age groups around the world. In recent years, the underlying
pathophysiologic mechanisms potentially common to both headaches and epileptic
seizures have been the subject of scrutiny. The objective of this study was to
determine the frequencies and types of headaches in patients with epilepsy, and
evaluate any temporal relationship with epileptic seizures. METHOD: Demographic
data, epilepsy durations, seizure frequencies, seizure types and antiepileptic
medications used were captured of 349 patients who were followed up at our
epilepsy outpatient clinic. Patients who experienced headaches were grouped based
on the type of headaches and on whether their headaches occurred in the preictal,
postictal or interictal period. RESULT: Three hundred forty-nine patients (190
females, 159 males) were enrolled in the study. The patients' average age was
30.9+/-13.1 years, and average epilepsy duration was 13.5+/-10.9 years. The types
of epileptic seizures were partial in 19.8% of patients, generalized in 57.9%,
and secondary generalized in 20.3% of patients. Some 43.6% of the patients did
not experience headaches, and 26.9% had migraine and 17.2% tension-type
headaches. Headaches could not be classified in 12.3% of patients. The headaches
occurred preictally in 9.6%, postictally in 41.6% and interictally in 8.6% of
patients. The ratio of headaches was lower in male patients compared with
females, and females experienced migraine-type headaches more frequently compared
with males (p=0.006). Migraine-type headaches were less frequent a mong patients
who experienced less than one seizure per year, but more frequent (p=0.017) among
those who experienced more than one seizure per month, but less than one seizure
per week. Migraine-type headaches were significantly more frequent (p=0.015)
among patients receiving polytherapy compared with patients receiving
monotherapy. CONCLUSION: The results of this study suggest that headaches,
particularly migraine-type headaches, were frequently experienced by patients
with epilepsy, postictal headaches were more common, and the frequency of
migraine attacks could be linked with seizure frequency and the type of
treatment.
PMID- 28427027
TI - Multisensory temporal function and EEG complexity in patients with epilepsy and
psychogenic nonepileptic events.
AB - Cognitive and perceptual comorbidities frequently accompany epilepsy and
psychogenic nonepileptic events (PNEE). However, and despite the fact that
perceptual function is built upon a multisensory foundation, little knowledge
exists concerning multisensory function in these populations. Here, we
characterized facets of multisensory processing abilities in patients with
epilepsy and PNEE, and probed the relationship between individual resting-state
EEG complexity and these psychophysical measures in each patient. We
prospectively studied a cohort of patients with epilepsy (N=18) and PNEE (N=20)
patients who were admitted to Vanderbilt's Epilepsy Monitoring Unit (EMU) and
weaned off of anticonvulsant drugs. Unaffected age-matched persons staying with
the patients in the EMU (N=15) were also recruited as controls. All participants
performed two tests of multisensory function: an audio-visual simultaneity
judgment and an audio-visual redundant target task. Further, in the cohort of
patients with epilepsy and PNEE we quantified resting state EEG gamma power and
complexity. Compared with both patients with epilepsy and control subjects,
patients with PNEE exhibited significantly poorer acuity in audiovisual temporal
function as evidenced in significantly larger temporal binding windows (i.e.,
they perceived larger stimulus asynchronies as being presented simultaneously).
These differences appeared to be specific for temporal function, as there was no
difference among the three groups in a non-temporally based measure of
multisensory function - the redundant target task. Further, patients with PNEE
exhibited more complex resting state EEG patterns as compared to their patients
with epilepsy, and EEG complexity correlated with multisensory temporal
performance on a subject-by-subject manner. Taken together, findings seem to
indicate that patients with PNEE bind information from audition and vision over
larger temporal intervals when compared with control subjects as well as patients
with epilepsy. This difference in multisensory function appears to be specific to
the temporal domain, and may be a contributing factor to the behavioral and
perceptual alterations seen in this population.
PMID- 28427028
TI - Terminal seizure frequency and its relation to SUDEP.
AB - BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a major cause of death
in patients with epilepsy. Several risk factors have been implicated, including
early age of onset, tonic-clonic seizures and antiepileptic drugs. However,
whether patients who die from SUDEP have a greater frequency of seizures in the
few months before death is unclear. We investigated the terminal seizure
frequency and its relation to SUDEP among a large group of patients with tonic
clonic seizures in rural West China. METHODS: We used the database from the
Convulsive Epilepsy Control and Management Program in West China, which routinely
provides phenobarbital (PB) as a treatment for convulsive epilepsy. Patients with
probable SUDEP were included according to pre-set criteria. A verbal autopsy was
undertaken for each case. By matching each patient's age, sex, date of joining
the program, time in follow-up, and baseline seizure frequency, we set up a 1:5
ratio control group. SPSS 21.0 statistics were applied to compare the differences
in seizure frequency 3months prior to SUDEP between patients with probable SUDEP
and controls. Furthermore, the dynamic changes of terminal seizure frequency 6
9months, 3-6months, and 3months prior to SUDEP was also analyzed. RESULTS: A
total of 41 patients who died from probable SUDEP were identified out of 7844
patients during 10years of follow-up. The SUDEP group had a significantly higher
tonic-clonic seizure frequency 3months before their deaths than the control group
(p=0.023). At the same time, their seizure-free rate was lower than the control
group (p=0.025). Patients with probable SUDEP who were followed up over 12months
were further studied as a subgroup. They had more tonic-clonic seizures 3months
prior to death compared to the control group (p=0.010). They also had an increase
in seizure frequency in their terminal phase (3months prior) compared to an
earlier stage (3-6months prior) (p=0.029). Furthermore, the terminal PB dose in
the SUDEP group was higher than the control group (p=0.002). CONCLUSION: Patients
who died from SUDEP had more frequent tonic-clonic seizures 3months before their
deaths. Higher seizure frequency increases the exposure to peri-ictal
pathophysiological events, which possibly relate to SUDEP. This phenomenon may be
due to the drug resistance potential of these patients or the high dose of PB.
Further research is required to ascertain the underlying mechanisms of SUDEP.
PMID- 28427029
TI - Treatment of refractory and super-refractory status epilepticus with
brivaracetam: A cohort study from two German university hospitals.
AB - PURPOSE: We aimed to ascertain the possible use of brivaracetam (BRV) as an
option for treatment of status epilepticus (SE). METHODS: A review of medical
records was carried out to detect BRV administration in SE patients treated in
Frankfurt and Greifswald during the period February 2016 to January 2017. The
primary outcome question concerned SE resolution after BRV initiation. RESULTS:
During that period, BRV was started with eleven adult patients with SE. Five of
these were female, and the median age was 64 (interquartile range [IQR] 21years).
The median SE duration before BRV initiation was 5days (IQR 9days); the median
number of previous anticonvulsants used was 4 (IQR 5). Initial BRV doses ranged
between 50mg and 400mg (median 100mg), titrated to a daily dose of 100 to 400mg
(median 200mg). There was a cessation of SE in the first 24h of BRV in three
patients (27%). While taking BRV, no serious side effects were seen. CONCLUSION:
Based on these cases and previous data from animal experiments, BRV may prove
useful in SE treatment, and trials would be warranted to examine BRV's efficacy
in treating SE and how this efficacy might be influenced by co-administration
with levetiracetam.
PMID- 28427030
TI - The relationship between sign production and sign comprehension: What handedness
reveals.
AB - Unlike the phonological loop in spoken language monitoring, sign language users'
own production provides mostly proprioceptive feedback and only minimal visual
feedback. Here we investigate whether sign production influences sign
comprehension by exploiting hand dominance in a picture-sign matching task
performed by left-handed signers and right-handed signers. Should all signers
perform better to right-handed input, this would suggest that a frequency effect
in sign perception drives comprehension. However, if signers perform better to
congruent-handed input, this would implicate the production system's role in
comprehension. We found evidence for both hypotheses, with variation dependent on
sign type. All signers performed faster to right-handers for phonologically
simple, one-handed signs. However, left-handed signers preferred congruent-handed
input for phonologically complex, two-handed asymmetrical signs. These results
are in line with a weak version of the motor theory of speech perception, where
the motor system is only engaged when comprehending complex input.
PMID- 28427031
TI - Executive function depletion in children and its impact on theory of mind.
AB - The current studies provide an experimental, rather than correlational, method
for testing hypotheses about the role of executive function (EF) in conceptual
development. Previous research has established that adults' tendency to deploy EF
can be temporarily diminished by use. Exercising self-control in one context
decreases adults' performance on other EF demanding tasks immediately thereafter.
Using two different depletion methods, Experiments 1 and 3 extend this finding to
preschool-aged children. Experiments 2 and 4 make use of these EF depletion
methods to elucidate the role of EF in children's theory of mind reasoning.
Experiment 2 shows that EF depletion affects 5-year-olds' ability to predict
another's behavior on the basis of that person's false belief, and Experiment 4
shows that this negative effect of depletion extends to 4- and 5-year-olds'
ability to explain others' behavior on the basis of their false beliefs. These
findings provide direct evidence that EF is required for the expression of an
understanding of others' false beliefs across a variety of task demands, even in
children who clearly have the capacity to construct such representations. We
suggest ways in which depletion may be used as a tool for further investigating
the role of executive function in cognitive development.
PMID- 28427032
TI - Social cognition in bipolar disorder: Focus on emotional intelligence.
AB - BACKGROUND: The present study aims to characterize emotional intelligence (EI)
variability in a sample of euthymic bipolar disorder (BD) patients through the
Mayer- Salovey-Caruso Emotional Intelligence Test (MSCEIT). METHOD: A total of
134 euthymic BD outpatients were recruited and divided into three groups
according to the total Emotional Intelligence Quotient (EIQ) score of the MSCEIT,
following a statistical criterion of scores 1.5SDs above/below the normative
group mean, as follows: a low performance (LP) group (EIQ <85), a normal
performance (NP) group (85<=EIQ<=115), and a high performance (HP) group (EIQ
>115). Afterwards, main sociodemographic, clinical, functional and neurocognitive
variables were compared between the groups. RESULTS: Three groups were
identified: 1) LP group (n=16, 12%), 2) NP group (n=93, 69%) and 3) HP group
(n=25, 19%). There were significant differences between the groups in premorbid
intelligence quotient (IQ) (p=0.010), axis II comorbidity (p=0.008), subthreshold
depressive symptoms (p=0.027), general functioning (p=0.013) and in four specific
functional domains: autonomy, occupation, interpersonal relations and leisure
time. Significant differences in neurocognitive performance were found between
groups with the LP group showing the lowest attainments. LIMITATIONS: The cross
sectional design of the study. CONCLUSION: Our results suggest that EI
variability among BD patients, assessed through MSCEIT, is lower than expected.
EI could be associated with premorbid IQ, subthreshold depressive symptoms,
neurocognitive performance and general functioning. The identification of
different profiles of SC may help guide specific interventions for distinct
patient subgroups aimed at improving social cognition, neurocognitive performance
and psychosocial functioning.
PMID- 28427033
TI - Toxicity of sulfadiazine and copper and their interaction to wheat (Triticum
aestivum L.) seedlings.
AB - A pot experiment was carried out to investigate the single and combined effect of
different concentrations of sulfadiazine (SDZ) (1 and 10mgkg-1) and copper (Cu)
(20 and 200mgkg-1) stresses on growth, hydrogen peroxide (H2O2), malondialdehyde
(MDA), antioxidant enzyme activities of wheat seedlings and their accumulation.
High SDZ or Cu level significantly inhibited the growth of wheat seedlings, but
the emergence rate was only inhibited by high SDZ level. The presence of Cu
reduced the accumulation of SDZ, whereas the effect of SDZ on the accumulation of
Cu depended on their concentrations. Low Cu level significantly increased the
chlorophyll content, while high Cu level or both SDZ concentrations resulted in a
significant decrease in the chlorophyll content as compared to the control.
Additionally, H2O2 and MDA contents increased with the elevated SDZ or Cu level.
The activities of superoxide dismutase, peroxidase and catalase were also
stimulated by SDZ or Cu except for the aerial part treated by low Cu level and
root treated by high SDZ level. The joint toxicity data showed that the toxicity
of SDZ to wheat seedlings was generally alleviated by the presence of Cu, whereas
the combined toxicity of SDZ and Cu was larger than equivalent Cu alone.
PMID- 28427034
TI - Taxometric analyses and predictive accuracy of callous-unemotional traits
regarding quality of life and behavior problems in non-conduct disorder
diagnoses.
AB - Callous-unemotional (CU) traits have mainly been studied in relation to conduct
disorder (CD), but can also occur in other disorder groups. However, it is
unclear whether there is a clinically relevant cut-off value of levels of CU
traits in predicting reduced quality of life (QoL) and clinical symptoms, and
whether CU traits better fit a categorical (taxonic) or dimensional model.
Parents of 979 youths referred to a child and adolescent psychiatric clinic rated
their child's CU traits on the Inventory of Callous-Unemotional traits (ICU), QoL
on the Kidscreen-27, and clinical symptoms on the Child Behavior Checklist.
Experienced clinicians conferred DSM-IV-TR diagnoses of ADHD, ASD, anxiety/mood
disorders and DBD-NOS/ODD. The ICU was also used to score the DSM-5 specifier
'with limited prosocial emotions' (LPE) of Conduct Disorder. Receiver operating
characteristic (ROC) analyses revealed that the predictive accuracy of the ICU
and LPE regarding QoL and clinical symptoms was poor to fair, and similar across
diagnoses. A clinical cut-off point could not be defined. Taxometric analyses
suggested that callous-unemotional traits on the ICU best reflect a dimension
rather than taxon. More research is needed on the impact of CU traits on the
functional adaptation, course, and response to treatment of non-CD conditions.
PMID- 28427035
TI - Associations between executive functions and mental health outcomes for adults
with autism spectrum disorder.
AB - Associations between executive functions (EF) and mental-health in adults with
autism spectrum disorder (ASD) were examined. Forty-two adults with ASD completed
measures of EF, mood and self-concept. Better concept formation and social
inference skills were significantly associated with fewer anxiety symptoms.
Conversely, participants with better non-verbal reasoning, cognitive flexibility
and social cognition reported more negative self-concept and lower self-esteem.
Overall, individuals with impaired EF are more prone to anxiety, whereas those
with stronger EF are more likely to experience negative self-concept. Screening
for and monitoring mental-health concerns in people with ASD regardless of their
level of EF is recommended.
PMID- 28427036
TI - The dose-dependent effect of zearalenone on mitochondrial metabolism, plasma
membrane permeabilization and cell cycle in human prostate cancer cell lines.
AB - Zearalenone (ZEA) is a nonsteroidal mycotoxin produced by several fungi of the
genus Fusarium spp. It is known to play various roles in the regulation of the
prostate cancer cell cycle, including carcinogenesis. The present study evaluates
the influence of ZEA on the mitochondrial metabolism, plasma membrane
permeabilization and cell cycle of prostate cancer cells. At concentrations of
100 nM and 0.3 nM, ZEA caused a decrease in the oxidative activity of
mitochondria, as well as increases in LDH release, apoptosis induction and the
number of cells in the G0/G1 phase. The opposite effect was observed for lower
concentrations (0.1 nM and 0.001 nM). These in vitro studies indicate that ZEA
might have pro- and antiproliferative properties in prostate cancer cells, at
concentrations 0.1 nM, 0.001 nM and 0.3 nM, 100 nM, respectively.
PMID- 28427037
TI - Monitoring of styrene oligomers as indicators of polystyrene plastic pollution in
the North-West Pacific Ocean.
AB - Styrene oligomers (SOs) as global contaminants are an environmental concern.
However, little is known on the distribution of SOs in the ocean. Here, we show
the distribution of anthropogenic SOs generated from discarded polystyrene (PS)
plastic monitored from the coastal ocean surface waters (horizontal distribution)
and deep seawaters (vertical distribution) in the North-West Pacific Ocean. SOs
concentrations in surface seawater and deep seawater ranged from 0.17 to 4.26 MUg
L-1 (total mean: 1.48 +/- 1.23 MUg L-1) and from 0.31 to 4.31 MUg L-1 (total
mean: 1.32 +/- 0.87 MUg L-1), respectively. Since there is no significant
difference in the mean concentrations, SOs seems to be spread across marine
environment selected in this study. Nevertheless, regional SOs appears to persist
to varying degrees with their broad horizontal and vertical distribution in the
ocean. Each horizontal and vertical distribution of SOs differs by approximately
1.95-2.57 times, probably depending on the events of weather and global ocean
circulation. These results provide the distribution pattern of SOs for assessing
environmental pollution arising from PS plastic.
PMID- 28427038
TI - Urinary triclosan concentrations during pregnancy and birth outcomes.
AB - BACKGROUND: Triclosan is an antimicrobial chemical used in consumer products, and
exposure is ubiquitous among pregnant women in the United States. Triclosan may
reduce the levels of thyroid hormones that are important for fetal growth and
development. OBJECTIVE: We investigated the relationship of prenatal triclosan
exposure with birth anthropometry and gestational duration. METHODS: We used data
from 378 mother-child pairs participating in the Health Outcomes and Measures of
the Environment (HOME) Study, a prospective pregnancy and birth cohort from
Cincinnati, OH. We measured triclosan concentrations in maternal urine samples
collected at 16 and 26 weeks of pregnancy. We abstracted information on neonatal
anthropometry and gestational duration from medical records. We used
multivariable linear regression to estimate the covariate-adjusted association
between the average of the two urinary triclosan concentrations and gestational
age standardized weight z-score, length, head circumference, and gestational age
at birth. RESULTS: Median urinary triclosan concentrations were 16ng/mL (range:
<2.4 to 1501ng/mL). Each 10-fold increase in triclosan was associated with a
predicted 0.15 standard deviation decrease (95% CI: -0.30, 0.00) in birth weight
z-score, 0.4-cm decrease (95% CI: -0.8, 0.1) in birth length, 0.3-cm decrease
(95% CI: -0.5, 0.0) in head circumference, and 0.3-week decrease (95% CI: -0.6,
0.1) in gestational age. Child sex did not modify the associations between
triclosan and birth outcomes. CONCLUSIONS: In this cohort, maternal urinary
triclosan concentrations during pregnancy were inversely associated with infants'
birth weight, length, head circumference, and gestational age.
PMID- 28427039
TI - Low dose growth hormone treatment in infants and toddlers with Prader-Willi
syndrome is comparable to higher dosage regimens.
AB - OBJECTIVE: Evaluate benefit and risk of low dose growth hormone treatment (GHT,
4.5mg/m2/week) in very young children with Prader-Willi Syndrome (PWS). DESIGN:
Prospective longitudinal clinical intervention. METHODS: We evaluated 31 infants
(aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for
height, weight and BMI using the World Health Organization standard deviation
scores (SDSWHO) and PWS specific BMI (SDSPWS), bone age, insulin-like growth
factor 1 (IGF-I) levels and adverse events over 3years of GHT. RESULTS: At
commencement of GHT infants had a lower BMI SDSWHO (-0.88 vs 0.40) than toddlers,
while toddlers had a lower height SDSWHO (-1.44 vs -2.09) (both P<0.05). All
increased height SDSWHO (2year delta height infants +1.26 SDS, toddlers+1.21
SDS), but infants normalised height sooner, achieving a height SDS of -0.56
within 1year, while toddlers achieved a height SDS of -0.88 in two years. BMI
SDSWHO increased, while BMI SDSPWS decreased (both P<0.0001) and remained
negative. The GHT response did not differ with gestation (preterm 23%) or genetic
subtype (deletion vs maternal uniparental disomy). Bone age advancement
paralleled chronological age. All children had low serum IGF-I at baseline which
increased, but remained within the age-based reference range during GHT (for 81%
in first year). Four children had spinal curvature at baseline; two improved, two
progressed to a brace and two developed an abnormal curve over the observation
period. Mild to severe central and/or obstructive sleep apnoea were observed in
40% of children prior to GHT initiation; 11% commenced GHT on positive airway
pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or
worsening of sleep apnoea: 2 infants in the first few months and 6 children after
6-24months. Seven resumed GHT usually after adjusting PAP but five had
adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness.
No other adverse events were reported. Two children substantially improved their
breathing shortly after GHT initiation. CONCLUSION: Initiation of GHT in infants
with 4.5mg/m2/week was beneficial and comparable in terms of auxological response
to a dose of 7mg/m2/week. Regular monitoring pre and post GH initiation assisted
in early detection of adverse events. IGF-I levels increased with the lower dose
but not excessively, which may lower potential long-term risks.
PMID- 28427040
TI - Cortex Mori Radicis extract attenuates myocardial damages in diabetic rats by
regulating ERS.
AB - Diabetic cardiomyopathy (DCM) is diagnosed when patients with diabetes develop
ventricular dysfunction but do not exhibit coronary atherosclerosis or
hypertension. Cortex Mori (CM) Radicis,he epidermis of the root of Morus alba L,
has been traditionally used for cough treatment in oriental medicine. In this
study, we investigated the protection of myocardium by CM in streptozotocin (STZ)
induced diabetic rats and the underlying mechanisms. Diabetes was induced in rats
by an injection of STZ at 25mg/kg. The animals were randomly divided into 4
groups: control, diabetes, diabetes with CM treatment, diabetes with CM
preventative treatment. Pathological changes were examined by hematoxylin-eosin
staining. Extracellular matrix content was assessed by Masson's trichrome
staining and Western blot. Endoplasmic reticulum (ER) stress-associated molecules
and main components of the mitogen-activated protein kinase (MAPK) pathway were
also measured by Western blot. Myocardial damages were induced by the injection
of STZ as evidenced by abnormal blood glucose and pathological cardiac changes.
Administration of CM markedly ameliorated myocardial damages such as cardiac
hypertrophy and fibrosis. ER stress was down-regulated, and p38 and ERK were
suppressed by CM. Thus, CM may have therapeutic potential in the treatment of DCM
by attenuating ER stress and ERK and p38 MAPK activation.
PMID- 28427042
TI - Long-term performance assessment of HPGE detectors used in the neutron activation
analysis laboratory of IPEN-CNEN/SP (Brazil).
AB - In this work, verification data for 11 HPGe detectors from two different
manufacturers and three different intrinsic configurations were analyzed in
respect to the stability of both the efficiency and resolution for the 122keV
peak from 57Co and the 1332keV peak from 60Co. The results allow a discussion
about the stability of these parameters over time (in some cases, almost 15
years), their sensitivity to imminent detector failures and their performance
after a failure has been corrected; moreover, the results show a clear
correlation between the manufacturer or configuration and the long-term
performance of the detector.
PMID- 28427041
TI - The efficacy of donepezil administration on acetylcholinesterase activity and
altered redox homeostasis in Alzheimer's disease.
AB - Alzheimer's disease (AD) is a serious multifactorial disorder with progressive
neurodegenerative outcomes related with impaired redox homeostasis. Inhibition of
the enzyme acetylcholinesterase (AChE), as one of the major therapeutic
strategies, is considered to be offering only symptomatic relief and moderate
disease modifying effect. We intended to investigate the effects of
acetylcholinesterase inhibition via donepezil on protein carbonyl (PCO), advanced
protein oxidation products (AOPP) and ischemia modified albumin (IMA) as protein
oxidation markers and ferric reducing antioxidant power (FRAP), prooxidant
antioxidant balance (PAB), total thiol (T-SH), protein thiol (P-SH) as
antioxidant status markers and also kynurenine (KYN), N-formyl kynurenine (N
FKYN) and protein bound dityrosine (DT) levels all in one demonstrating the redox
homeostasis in Alzheimer patients also correlated with AChE activity. The AChE
activity and PCO, KYN, N-FKYN and DT levels were found to be significantly higher
in the AD group than the control group. The FRAP, T-SH and P-SH levels were
significantly lower in the AD group than in the control group. The AChE activity
was significantly higher both in donepezil treated and untreated groups when
compared with the control group. PCO levels were significantly higher in
Alzheimer's untreated group than the healthy control and donepezil treated
groups. AChE activity was positively correlated with PCO, IMA, PAB, KYN and N
FKYN levels and negatively correlated with FRAP, T-SH and P-SH levels in all
participants. Our data showed that treatment with donepezil had ameliorating
effects on redox homeostasis in Alzheimer patients. AChE inhibition seems to be
exhibiting a potent antioxidant role and may inhibit protein oxidation by
decreasing AChE activity in AD, thus medicinal natural substances exhibiting the
similar mechanism of action with their antioxidant behaviours can be recommended
for the emphasis on new drug new drug development. Further clinical and
experimental studies are needed to support our current findings and conclusions.
PMID- 28427043
TI - Neutron radiation shielding properties of polymer incorporated self compacting
concrete mixes.
AB - In this work, the neutron radiation shielding characteristics of a class of novel
polymer-incorporated self-compacting concrete (PISCC) mixes are evaluated.
Pulverized high density polyethylene (HDPE) material was used, at three different
reference volumes, as a partial replacement to river sand in conventional
concrete mixes. By such partial replacement of sand with polymer, additional
hydrogen contents are incorporated in these concrete mixes and their effect on
the neutron radiation shielding properties are studied. It has been observed from
the initial set of experiments that there is a definite trend of reductions in
the neutron flux and dose transmission factor values in these PISCC mixes vis-a
vis ordinary concrete mix. Also, the fact that quite similar enhanced shielding
results are recorded even when reprocessed HDPE material is used in lieu of the
virgin HDPE attracts further attention.
PMID- 28427044
TI - On the reverse micelle effect in liquid scintillation counting.
AB - This work looks into the tracks of electrons in nanoemulsive scintillating media
using the Monte Carlo Geant4-DNA code which simulates event-by-event interactions
of electrons in liquid water down to the eV, without resorting to the condensed
history method. It demonstrates that the average number of micelles in which
electrons deposit energy is quite large, increasing with their emission energy,
decreasing with micelle size, and rising with micelle concentration. The
probability of an electron ending its track in a micelle is found to be rather
large and micelle size-dependent below 1keV, and approximating the aqueous
fraction at higher energies. Analyses of the Monte Carlo estimated energy
depositions in the aqueous phase and in the scintillant tell of a micelle
quenching effect, with the micelle size shaping the quenching at low energy and
the micelle concentration governing it at higher energies. The micelle effect on
the 3H and 63Ni beta spectra is discussed for a range of micelle sizes and
concentrations. This paper also computes the ionisation quenching function using
Birk's law whilst considering the full energy losses in the micelles bisecting
the electron pathway, and not just that incurred in the primary micelle enclosing
the decaying nuclide. The ionisation quenching function is then used to calculate
the detection efficiencies for 3H, 63Ni, 54Mn and 55Fe. The effect of the micelle
size is found to be small for beta emitters but significant for the electron
capture nuclides. TDCR measurements of 63Ni samples covering 8 aqueous fractions
are analysed with and without explicit treatment of the micelle effect.
Activities in the two representations agree within 0.02%. The ratios of the
corresponding figures of merit are found to coincide with the scintillant
fractions.
PMID- 28427045
TI - MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting
HMGB1-Mediated Autophagy.
AB - BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high
mortality rate. Drug resistance represents a main obstacle in NSCLC treatment.
High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells
by activating protective autophagy. METHODS: In the current study, we
investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1
mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in
vitro and in vivo. HMGB1 was identified as a putative target gene of miR-142-3p
by in silico analysis. Our luciferase reporter assay results confirmed that miR
142-3p directly targets the 3'-UTR of HMGB1 in NSCLC cells. RESULTS: MiR-142-3p
overexpression suppressed while miR-142-3p knockdown increased HMGB1 mRNA and
protein expression. Starvation induced HMGB1 expression and activated autophagy
in NSCLC cells. The starvation-induced autophagy was inhibited by miR-142-3p
overexpression or HMGB1 knockdown. Moreover, miR-142-3p overexpression or HMGB1
knockdown increased PI3K, Akt, and mTOR phosphorylation. Inhibition of PI3K or
mTOR restored starvation-induced autophagy inhibited by miR-142-3p overexpression
or HMGB1 knockdown. CONCLUSIONS: These results demonstrated that miR-142-3p
regulates starvation-induced autophagy of NSCLC cells by directly downregulating
HMGB1 and subsequently activating the PI3K/Akt/mTOR pathway. Further, miR-142-3p
overexpression inhibited anticancer drug-induced autophagy and increased chemo
sensitivity of NSCLC in vitro and in vivo. These findings shed light on the
therapeutic potential of miR-142-3p in combating acquired NSCLC chemo-resistance.
PMID- 28427046
TI - Impressive Response to Pixantrone after Allogeneic Transplant in a Multiple
Relapsed Diffuse Large B-Cell Lymphoma.
AB - Diffuse large B-cell lymphoma is the most frequent histology at diagnosis among
non-Hodgkin B lymphomas and can be cured in 50-70% of cases after the first-line
chemotherapy regimen. Patients who do not respond to first-line treatment can
undergo numerous subsequent steps, culminating in allogeneic stem cell transplant
(alloSCT). A relapse after alloSCT, however, carries an awful prognosis, seeing
the demise of the patient usually in the following months. Here we present the
case of a multiple relapsed patient who successfully underwent therapy with
pixantrone after alloSCT, obtaining a complete remission without any considerable
side effects.
PMID- 28427047
TI - Co-Activation of TGFbeta and Wnt Signalling Pathways Abrogates EMT in Ovarian
Cancer Cells.
AB - BACKGROUND/AIMS: The aggressive property of ovarian cancer (OC) in terms of
epithelial-mesenchymal transition (EMT), proliferation and metastasis are of
major concern. Different growth factors including TGFbeta are associated with
regulating these molecular events but the underlying mechanisms remain unclear.
The aim of this report is to decipher the regulation of EMT by co-activation of
TGFbeta and Wnt signalling cascades in gaining malignancy. METHODS: The
expression of the different components of signalling events were analyzed by
QPCR, Western blot, Immunofluorescence microscopy and flow cytometry. beta
catenin promoter activity was checked by luciferase assay. RESULTS: We observed
reduced EMT in ovarian cancer cells upon co-activation with TGFbeta1 and LiCl as
shown by the expressions of epithelial/mesenchymal markers and the EMT promoting
factor, Snail1, accompanied by decrease in the invasion and migration of the
cells compared to individual pathway activation. A detailed study of the
mechanism suggested reduction in the beta-catenin and p-GSK3b (Ser 9) levels to
be the driving cause of this phenomenon, which was reversed upon co-activation
with higher concentrations of LiCl. CONCLUSIONS: Therefore, tumourigenesis might
be affected by the concentration of ligand/ growth factors for the respective
signalling pathways activated in the tumour microenvironment and interaction
between them might alter tumourigenesis.
PMID- 28427048
TI - 1,25-Dihydroxyvitamin D3 Attenuates the Effects of Lipopolysaccharide by Causing
ADAM10-Dependent Ectodomain Shedding of Toll-Like Receptor 4.
AB - BACKGROUND/AIMS: We investigated how 1,25-dihydroxyvitamin D3 (1,25D3) inhibits
the effects of lipopolysaccharide (LPS) in human aortic endothelial cells.
METHODS: Cellular signaling was explored by determination of protein abundance
with Western blot, measurement of cytosolic Ca2+ concentration and
immunofluorescence staining for a disintegrin and metalloprotease 10 (ADAM10).
RESULTS: LPS stimulated the expression of intercellular adhesion molecule 1 (ICAM
1) through toll-like receptor 4 (TLR4) and subsequent activation of p38 mitogen
activated protein kinase (p38 MAPK). Pretreatment with 1,25D3 attenuated LPS
induced p38 MAPK activation and ICAM-1 expression by causing ectodomain shedding
of TLR4. This effect of 1,25D3 depended on its ability to induce a rapid
extracellular Ca2+ influx through L-type calcium channels because the ectodomain
shedding was prevented by the absence of extracellular Ca2+ or the presence of
verapamil. TLR4 ectodomain shedding was also induced by Bay K8644 (L-type calcium
channel agonist). Both 1,25D3 and Bay K8644 caused extracellular Ca2+ influx
dependent ADAM10 translocation to the cell surface. Depletion of ADAM10 by siRNA
transfection prevented 1,25D3- and Bay K8644-induced ectodomain shedding of TLR4,
and abolished the inhibitory effect of 1,25D3 on LPS-induced ICAM-1 expression.
CONCLUSION: 1,25D3 causes ectodomain shedding of TLR4 and thereby decreases the
responsiveness of cells to LPS. ADAM10, activated by extracellular Ca2+ influx,
was implicated in the ectodomain cleavage of TLR4.
PMID- 28427049
TI - Predictive Validity of Two Physical Frailty Phenotype Specifications Developed
for Investigation of Frailty Pathways in Older People.
AB - BACKGROUND: For investigating the relationship of frailty with physical,
psychological, and social conditions on pathways, the frailty definition should
ideally exclude these conditions. Based on the frailty phenotype, 2 candidate
physical frailty specifications or instruments with 3 indicators, namely
slowness, weakness, and exhaustion, and 4 indicators with addition of weight loss
were previously developed, and had their construct and concurrent validity
demonstrated. OBJECTIVE: This study seeks to evaluate the predictive validity of
2 candidate physical frailty specifications with respect to death, functional
impairment, and poor quality of life in older people. METHODS: For 4,368
respondents aged 65-89 years from wave 2 of the English Longitudinal Study of
Ageing, confirmatory factor analysis is performed for these 2 physical frailty
specifications to obtain unique factor scores for each respondent. Prediction of
death, basic and instrumental activities of daily living (BADL and IADL)
difficulty, and poor quality of life (reverse of Control, Autonomy, Self
realization, and Pleasure [19 items] or CASP-19) 2 years later by factor scores
for these 2 specifications is evaluated using standardized coefficients, c
statistics, and r2 values from regression analyses. Their performance is compared
with those of alternative specifications with 3 (slowness, weakness, and weight
loss) and 5 indicators (slowness, weakness, exhaustion, weight loss, and low
physical activity), and Frailty Index (FI). RESULTS: For the 2 candidate
specifications, an increase of 1 standard deviation (SD) predicts 50-57% increase
in odds of death, 0.10-15 SD increase in change in BADL or IADL difficulty, and
poor quality of life at 2 years. They predict these outcomes as well or better
than the alternative specification with 3 indicators, but marginally worse than
that with 5 indicators. Compared with FI, they predict death and poor quality of
life similarly, but perform worse for functional impairment. Minor differences
are observed across gender. CONCLUSION: Reasonable predictive validity of 2
candidate physical frailty specifications based on the frailty phenotype with 3
and 4 indicators is demonstrated for death, functional impairment, and poor
quality of life. These findings offer evidence to support their suitability for
employment in investigating frailty pathways in older people.
PMID- 28427050
TI - Expression of High Mobility Group Protein B1 in Cardiac Tissue of Elderly
Patients with Coronary Artery Disease with or without Inflammatory Rheumatic
Disease.
AB - BACKGROUND: It is known from clinical practice and observational studies that
elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a
significantly increased risk for cardiovascular diseases such as coronary artery
disease (CAD) and heart failure. The molecular mechanism, however, is still not
known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly
conserved single polypeptide expressed in all mammal eukaryotic cells, has been
identified to mediate myocardial dysfunction in vitro once released from the
nuclei of cardiomyocytes. OBJECTIVE: To investigate whether HMGB1 and its
receptors are expressed in cardiac muscles of elderly patients with CAD with or
without IRD. METHODS: HMGB1 and its 3 well-known receptors, receptor for advanced
glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by
immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with
CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were
measured by Western blot from the cardiac biopsies in 5 patients with and 5
without IRD. RESULTS: Pathologic cytosolic HMGB1 in cardiomyocytes was massively
recorded in all patients with IRD, but only slightly expressed in 1 patient
without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle
biopsies of patients with IRD compared to those without IRD. Furthermore, all 3
HMGB1 receptors were expressed in cardiomyocytes of all patients. CONCLUSION: The
increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total
amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a
greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD
individuals. Thus, the HMGB1 signaling pathways may be more easily activated in
elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory
process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD
patients might reduce the risk for cardiovascular events.
PMID- 28427051
TI - Subjective Time Perceptions and Aging Well: A Review of Concepts and Empirical
Research - A Mini-Review.
AB - Human beings impose subjective, time-related interpretations on their existence,
and the experience of time is a major aspect of lifespan development. In this
mini-review, we understand subjective time as the way individuals subjectively
perceive and evaluate the passing of their personal "objective" lifetime. A broad
range of constructs and operationalizations has been developed in (gero-)
psychology to capture subjective time, including future time perspective,
personal goals, or autobiographical memories. In order to theoretically integrate
this yet loosely connected body of literature, we propose a conceptual model of
subjective time concepts according to 2 dimensions: temporal direction (past,
present, future) and thematic field (duration/expansion, time-ordered life
content, and time-related evaluations, attitudes, and mindsets). This conceptual
model of subjective time perceptions builds the foundation for a review of the
empirical literature regarding associations of subjective time with developmental
outcomes (i.e., subjective well-being and physical health) in middle and late
adulthood. Empirical findings establish subjective time concepts as a consistent
predictor of well-being and health. Positive subjective time perceptions (i.e.,
an expanded view of the future, a focus on positive past and future life content,
and favorable time-related evaluations) were associated with higher well-being
and better physical health, while negative subjective time perceptions in general
were linked to lower levels of health and well-being. Contrasting past- and
future-oriented subjective time perceptions, it appears that past-oriented
subjective time perceptions have been studied primarily in relation to subjective
well-being, while future-oriented time perceptions play a key role both with
regard to physical health and well-being. In conclusion, we argue that a stronger
integration of subjective time constructs into developmental regulation models
may deepen our understanding of human development across the lifespan. To this
end, we call for theoretical and empirical interlinkages between yet loosely
connected conceptual developments related to subjective time. These endeavors
should be paralleled by an extension of methodological procedures (e.g.,
implementation of longitudinal research designs as well as a focus on the oldest
old) in order to inform a "lifespan theory of subjective time."
PMID- 28427052
TI - Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis
Lungs.
AB - BACKGROUND: Cystic fibrosis (CF) is the most common autosomal-recessive disorder
in western countries. Previous studies have demonstrated an important role of
sphingolipids in the pathophysiology of cystic fibrosis. It has been shown that
ceramide has a central role in various pulmonary infections, including those with
Pseudomonas aeruginosa (P. aeruginosa). Ceramide is accumulated in the airways of
CF mice and patients. However, little is known about a potential role of
glucosylceramide in cystic fibrosis. METHODS: We investigated the expression of
glucosylceramide and lactosylceramide in the respiratory tract of murine and
human CF samples by immunohistochemistry and analyzed effects of glucosylceramide
on P. aeruginosa in vitro. We performed pulmonary infections with P. aeruginosa
and tested inhalation with glucosylceramide. RESULTS: We demonstrate that
glucosylceramide is down-regulated on the apical surface of bronchial and
tracheal epithelial cells in cystic fibrosis mice. Although glucosylceramide did
not have a direct bactericidal effect on Pseudomonas aeruginosa in vitro,
inhalation of CF mice with glucosylceramide protected these mice from infection
with P. aeruginosa, while non-inhaled CF mice developed severe pneumonia.
CONCLUSION: Our data suggest that glucosylceramide acts in vivo in concert with
ceramide and sphingosine to determine the pulmonary defense against P.
aeruginosa.
PMID- 28427053
TI - Growing Skull Fracture and the Orbitocranial Variant: Nuances of Surgical
Management.
AB - AIMS: Growing skull fracture (GSF) is a rare complication resulting from
diastatic enlargement of a pediatric skull fracture. Orbitocranial GSF is a
distinct variant with more complex management issues due to the displacement of
the globe. This study aims to discuss surgical considerations in the management
of GSF, with particular reference to orbitocranial variants. METHODS: We
conducted a retrospective analysis of 7 children operated for GSFs at our
institute from 2008 to 2015. RESULTS: Four boys and 3 girls were operated during
this period. The mean age at initial trauma was 2 years, and most of them
sustained falls. The most frequent symptoms of GSF were progressive scalp
swelling and proptosis. The most common location was the orbitofrontal region.
Duraplasty with cranioplasty was performed in 5 patients, while duraplasty alone
was only required in 2 patients. A postoperative complication was noted in 1
patient and managed successfully. Good cosmetic results were obtained in all of
the cases. CONCLUSIONS: Duraplasty is essential in the repair of GSF and should
be followed by cranioplasty to prevent recurrent leptomeningeal herniation. We
recommend the use of autologous bone from the surgical site for cranioplasty.
Orbital roof repair is advisable for good visual and cosmetic outcome in
orbitocranial variants of GSF.
PMID- 28427054
TI - Preceding Intravenous Thrombolysis in Patients Receiving Endovascular Therapy.
AB - BACKGROUND: The beneficial effects of endovascular therapy (EVT) in acute
ischemic stroke have been demonstrated in recent clinical trials using new
generation thrombectomy devices. However, the comparative effectiveness and
safety of preceding intravenous thrombolysis (IVT) in this population has rarely
been evaluated. METHODS: From a prospective multicenter stroke registry database
in Korea, we identified patients with acute ischemic stroke who were treated with
EVT within 8 h of onset and admitted to 14 participating centers during 2008
2013. The primary outcome was a modified Rankin Scale (mRS) score at 3 months.
Major secondary outcomes were successful recanalization defined as a modified
Treatment in Cerebral Ischemia score of 2b-3, functional independence (mRS score
0-2), mortality at 3 months, and symptomatic hemorrhagic transformation (SHT)
during hospitalization. Multivariable logistic regression analyses using
generalized linear mixed models were performed to estimate the adjusted odds
ratios (ORs) of preceding IVT. RESULTS: Of the 639 patients (male, 61%; age 69 +/
12; National Institutes of Health Stroke Scale score of 15 [11-19]) who met the
eligibility criteria, 458 received preceding IVT. These patients showed lower mRS
scores (adjusted common OR, 1.38 [95% CI 0.98-1.96]). Preceding IVT was
associated with successful recanalization (1.96 [1.23-3.11]) and reduced 3-month
mortality (0.58 [0.35-0.97]) but not with SHT (0.96 [0.48-1.93]). CONCLUSION: In
patients treated with EVT within 8 of acute ischemic stroke onset, preceding IVT
may enhance survival and successful recanalization without additional risk of
SHT, and mitigate disability at 3 months.
PMID- 28427055
TI - Aquaporin-4 Mediates the Suppressive Effect of Lipopolysaccharide on Hippocampal
Neurogenesis.
AB - OBJECTIVE: Aquaporin-4 (AQP4), a key molecule for water homeostasis in the brain,
is associated with adult neurogenesis, but its mechanisms regulating adult neural
stem cells (aNSC) remain largely unexplored. Neuroinflammation has a relevant
influence on adult neurogenesis, which is a common feature in various
neurodegenerative diseases. Considering the possible link between
neuroinflammation and AQP4, we speculate that AQP4 may mediate the synthesis and
release of proinflammatory cytokines in glia and then indirectly regulate adult
hippocampal neurogenesis. METHODS: Using AQP4 knockout mice, we investigated the
effects of AQP4 on hippocampal neurogenesis after lipopolysaccharide (LPS)
induced neuroinflammation. RESULTS: We unexpectedly found that AQP4 deficiency
attenuated the decrease in aNSC proliferation after systemic LPS exposure,
accompanied by inhibition of glial activation and suppression of the production
of proinflammatory cytokines in the hippocampus. Meanwhile, in vivo studies
demonstrated that LPS-induced activated microglia did not express AQP4,
indicating the impossibility of direct regulation of AQP4 to activate microglia.
Furthermore, we demonstrated in vitro that AQP4 deficiency inhibited astrocyte
activation and reduced the release of proinflammatory cytokines from astrocytes.
CONCLUSION: Our data suggest that AQP4 mediates the suppressive effect of
neuroinflammation on hippocampal neurogenesis via regulation of the astroglial
response.
PMID- 28427056
TI - Blood Pressure during the Immediate Neonatal Transition: Is the Mean Arterial
Blood Pressure Relevant for the Cerebral Regional Oxygenation?
AB - BACKGROUND: Measurement of mean arterial blood pressure (MABP) is feasible during
neonatal transition. OBJECTIVE: The objective of this study was to investigate a
potential influence of MABP on the cerebral regional oxygen saturation (crSO2) in
preterm and term infants during the immediate neonatal transition. MATERIALS AND
METHODS: Preterm and term infants were included in this observational study. The
crSO2 was measured by near-infrared spectroscopy with the INVOS 5100C (Somanetics
Corp., Troy, MI, USA) during the immediate neonatal transition (15 min after
birth). The near-infrared spectroscopy sensor was applied to the left forehead.
Furthermore, a pulse oximeter was applied to monitor arterial oxygen saturation
(SpO2) and heart rate (HR). Fifteen minutes after birth, blood pressure was
measured noninvasively at the left upper arm. Cerebral fraction tissue oxygen
extraction (cFTOE) was calculated from SpO2 and crSO2. To investigate a potential
association between crSO2/cFTOE and MABP, we performed a correlation analysis.
RESULTS: A total of 462 preterm and term infants (186/292) were included. Mean
gestational age was 31.0 +/- 3.5 weeks for preterm infants and 38.9 +/- 0.8 weeks
for full term infants. Mean birth weight was 1.591 +/- 630 g in preterm infants
and 3.331 +/- 461 g in term infants. There was a significant negative correlation
between MABP and cFTOE (rho = -0.19, p = 0.03) in preterm infants but not in term
infants (rho = 0.05, p = 0.39). There was no significant correlation between MABP
and crSO2 in either group. CONCLUSION: MABP has an impact on cerebral oxygenation
in preterm infants. Therefore, blood pressure monitoring during the immediate
neonatal transition might be relevant for improving cerebral oxygenation
especially in preterm infants.
PMID- 28427057
TI - Long-Term Anatomical and Functional Outcomes in Patients with Ischemic Central
Retinal Vein Occlusion Treated with Anti-Vascular Endothelial Growth Factor
Agents.
AB - PURPOSE: To evaluate the anatomical and functional outcomes in patients with
ischemic central retinal vein occlusion (CRVO) treated with intravitreal anti
vascular endothelial growth factor (VEGF) agents. METHODS: This retrospective
study included 15 treatment-naive patients with ischemic CRVO and macular edema
who were treated with intravitreal ranibizumab or aflibercept. The main outcomes
were the evolution of retinal ischemia over time, as well as the change in best
corrected visual acuity (BCVA) and in central subfield thickness (CST) at month
24. RESULTS: At month 24, patients with ischemic CRVO gained +7.8 letters
compared to baseline, while there was a significant decrease in CST by 243.7 MUm.
At baseline, ischemia was located mainly at the peripheral retina, while 6.6% of
patients presented macular ischemia. At month 24, 20% of patients had macular
ischemia, which was found to be negatively correlated with BCVA. The patients
with macular ischemia had very poor final visual outcome and were advised to
discontinue treatment. CONCLUSIONS: Our study showed that anti-VEGF treatment was
effective in patients with ischemic CRVO, since it reduces macular edema and
maintains or improves VA in the long term (24-month follow-up). It is worthy of
note that in a small proportion of patients (13.3%) peripheral ischemia
progressed to macular ischemia over time. In cases where macular ischemia is
present, anti-VEGF treatment does not seem to offer any improvement in VA.
PMID- 28427058
TI - Dietary Selenium or Zinc Supplementation Restores Brain Lipid Composition and
Membrane Fluidity in Protein-Undernourished Rats.
AB - Studies have shown that protein undernutrition (PU) modifies the membrane lipid
composition in the intestine and liver, as well as in plasma and other areas.
However, there is limited information on the effect of PU on synaptosomal
membrane lipid composition and fluidity and the protective role of selenium (Se)
and zinc (Zn), which is a major focus of the present study. For 10 weeks, rats
were fed diets containing 16% casein, which constituted the adequate protein
diet, or 5% casein, representing the PU diet. The animals were supplemented with
Se and Zn at a concentration of 0.15 and 227 mg L-1, respectively, in drinking
water for 3 weeks. The results showed a significant increase in total lipids,
glycolipids, triglycerides, cholesterol, and the cholesterol/phospholipid
(Chol/PL) ratio, and a significant reduction in phospholipids and membrane
fluidity. Se and Zn supplementation to PU rats, however, significantly lowered
total lipids, glycolipids, triglycerides, cholesterol, and the Chol/PL ratio,
while phospholipids and membrane fluidity were significantly restored. It is
concluded that a perturbed lipid composition induced by PU affects the membrane
structure and fluidity, which in turn influences membrane functions. The study
suggests that Se and Zn supplementation might be beneficial in restoring the
lipid dyshomeostasis associated with PU.
PMID- 28427059
TI - The Burden of Diabetes: Emerging Data.
AB - In recent times, the global prevalence of diabetes has increased substantially,
reaching 8.3% in 2014, which corresponds to 387 million patients. Studies in
Europe and USA have shown increased incidence of type 1 Diabetes (T1D) over time
at a rate of 3-5% per year. Another most worrying feature of the rapid increase
of diabetes is the emergence of type 2 Diabetes (T2D) in children, adolescents,
and young adults. The well-known behavioral risks factors and epigenetic
mechanisms recently observed require an integrated approach to prevent T2D.
Diabetes significantly influences the patient' survival, quality of life, and
development of organ system degeneration. Epidemiological studies have shown
increased mortality in diabetic patients, especially women, which increased
approximately fivefold, whereas cardiovascular mortality increased 20- to 30-fold
when compared to the normal population. Diabetes is the leading cause of end
stage renal disease and vision loss in developed countries. Around 40% of T1D and
T2D start on renal replacement therapy. While after 40 years of diabetes, the
cumulative proportion of patients with any retinopathy and advanced retinopathy
was 84.1 and 50.2%, respectively. However, the most prevalent chronic
complication of diabetes is neuropathy. Distal Symmetric Polyneuropathy occurs in
at least 20% of people with T1D after 20 years and in 10-15% of newly diagnosed
T2D, increasing to 50% after 10 years. Cardiovascular Autonomic Neuropathy may be
present in up to 60% of patients after 15 years and is an independent risk factor
for cardiovascular mortality.
PMID- 28427060
TI - The Eye as a Window to the Microvascular Complications of Diabetes.
AB - Although microvascular complications of diabetes (retinopathy, neuropathy, and
nephropathy) affect different organs, they are strongly correlated to each other.
Based on recent data, their onset and progression could be directly monitored,
focusing our attention only on the eye. When confirmed and standardized, this
approach could allow one to simplify the way in which we follow the progression
of different diabetic complications, and thus establish new strategies aimed at
preventing, treating and, hopefully, inducing the remission of microvascular
complications of diabetes.
PMID- 28427061
TI - Emerging Insights into Pathogenesis.
AB - Diabetic retinopathy (DR) is a frequent complication of diabetes mellitus (DM).
Persistent hyperglycemia leads to the activation of multiple cellular pathways
involved in the pathogenesis of DR, resulting in increased inflammation,
oxidative stress, and vascular dysfunction. DR has been considered a "chronic,
low-grade inflammatory disease of the retina". However, an increasing body of
evidence suggests that inflammation and neurodegeneration both occur in human
diabetes even before the development of clinical signs of DR. One of the first
signs of inflammation in DM is the activation of retinal glia cells (RGC). RGC
include microglia and macroglial cells (Muller cells and astrocytes). Activated
RGC release cytotoxic substances responsible for the recruitment of leukocytes,
blood-retinal barrier breakdown, direct glial dysfunction, and neuronal cell
death. Recently, many inflammatory mediators, growth factors, and other molecules
have been investigated in human vitreous and aqueous humor samples to better
understand, in vivo, the multiple pathways and mechanisms leading to the
pathogenesis of DR and its complications, such as diabetic macular edema, with
potential for more tailored treatment. Moreover, non-invasive techniques, like
optical coherence tomography, have allowed to detect new findings in the retinal
layers, such as the hyperreflective intraretinal spots, which have been
hypothesized to represent an in vivo marker of microglial activation, and early
neural cell loss, confirming the hypothesis that neurodegeneration occurs early
both in type 1 and 2 diabetes. These new emerging insights foster a better
understanding of the pathogenesis of DR, which can no longer be considered as a
pure retinal vascular complication of DM.
PMID- 28427062
TI - Emerging Issues for Optical Coherence Tomography.
AB - Almost 25 years after its introduction, optical coherence tomography (OCT) is
still a crucial test in the evaluation of patients affected by diabetic
retinopathy. In this chapter, the authors provide an extensive overview of the
posterior segment pathological changes induced by diabetes, characterized using
OCT. OCT plays a key role in diabetic macular edema (DME) as it assesses related
retinal changes both in a qualitative (i.e., DME pattern, presence and aspects of
cysts, fluid localization, integrity, and reflectivity of retinal layers) and
quantitative (i.e., macula volume, central and sectorial retinal thickness) way,
and it is therefore essential for diagnosis, characterization, and follow-up of
DME. Diabetic macular ischemia is associated with retinal structural changes
which can be investigated using OCT, although its diagnosis relies mostly on
fluorescein angiography. Beyond DME and macular ischemia, OCT permits the
individuation of many other lesions occurring in the setting of both non
proliferative (i.e., hyperreflective spots, micropseudocysts, hard exudates,
microaneurysm, cotton-wool spots) and proliferative (i.e., neovascularization,
vitreoschisis, tractional retinal detachment, hemorrhage) retinopathies. OCT
provides precious information on several structures, including vitreo-retinal
interface, retinal nerve fiber layers, ganglion cell complex, and choroid.
PMID- 28427063
TI - Optical Coherence Tomography Angiography in Diabetic Maculopathy.
AB - Fluorescein angiography (FA) and indocyanine green angiography have provided
information about the normal retinal and choroidal anatomy, nearly comparable to
histological findings. These tests have been fundamental in the evaluation of all
retinal and choroidal vascular diseases and have allowed clinicians to define and
diagnose several pathological conditions. FA became the "gold standard" in
retinal imaging due to the capacity to visualize the retinal capillary bed and
its changes, both in the macular area and in the periphery. Although the
fluorescence of the injected dye enabled improved visualization of retinal
capillaries, not all the different layers of the retinal capillary network could
be visualized in this bi-dimensional examination, mainly because of the light
scattering phenomenon. By calculating the difference between static and non
static tissues, optical coherence tomography angiography (OCT-A) allows a depth
resolved visualization of the retinal and choroidal microvasculature. Given that
the main moving elements in the ocular fundus are contained in blood vessels,
determining a vascular decorrelation signal enables visualization of the 3
dimensional retinal and choroidal vascular networks without the intravenous dye
injection, reducing therefore the risk of potential adverse events. Since OCT-A
is perfectly co-registered with its structural OCT, both morphological findings,
such as macular edema, and functional ones, like capillary drop-out, may be
clearly evaluated on a single dye-free examination. Proficient detection of the
different findings in diabetic maculopathy on OCT-A can result in a rapid
analysis of the examination, and in the capacity to distinguish truly
decorrelated structures (perfused vessels) from artifacts. Moreover, a complete
morpho-functional assessment may help in determining both the origin and the
clinical activity of a given vascular disease.
PMID- 28427064
TI - Emerging Issues for Ultra-Wide Field Angiography.
AB - Fluorescein angiography (FA) is a useful test in patients affected by diabetic
retinopathy (DR) to evaluate the blood-retinal barrier integrity and the presence
of non-perfused areas, vascular leakage, microvascular abnormalities, and
neovascularization. The peripheral retina is involved in most DR lesions, and,
thus, its proper visualization is crucial for the screening, diagnosis,
monitoring, treatment, and prognosis of DR. To expand the field of view, wide
field and ultra-wide-field imaging have been developed, allowing images up to 200
degrees of retinal surface in one single photo. In this chapter, emerging issues
concerning ultra-wide-field FA in DR are illustrated.
PMID- 28427065
TI - Emerging Simplified Retinal Imaging.
AB - Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a
significant impact on the world's health systems. Globally, the number of people
with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and it is
estimated that the number with vision-threatening diabetic retinopathy will
increase from 37.3 million to 56.3 million if prompt action is not taken. Lack of
early diagnosis and management is the leading cause of blindness in working-age
populations The gap between demand and annual eye examinations has been a big
challenge. Furthermore lack of availability of cost effective simplified retinal
imaging tools has limited the diabetic retinopathy screening program in many
parts of the world in last few decades. This has led to the development of
innovative ideas and availability of cost effective simplified retinal imaging
tools. In this chapter we will be describing some of the well known commercially
available emerging simplified (Non Tabletop, Hand Held, Portable) retinal imaging
tools that have potential to help in screening diabetic retinopathy with ease and
without increasing financial burden.
PMID- 28427066
TI - Intravitreal Ranibizumab in Diabetic Macular Edema: Long-Term Outcomes.
AB - Intravitreal ranibizumab (RBZ) has been shown in multiple randomized clinical
trials to be a valuable treatment for diabetic macular edema (DME), promoting a
significant improvement in best-corrected visual acuity (BCVA) and in anatomic
outcomes. Compared to sham (RISE and RIDE studies), RBZ rapidly and sustainably
improved BCVA and decreased macular edema at 2 years, reducing the risk of
further vision loss, with low rates of local or systemic side effects. Compared
to macular laser photocoagulation (READ-2 study), RBZ provided a greater
improvement in BCVA and regression in foveal thickness, but required a higher
number of injections compared to patients treated with both RBZ and laser. In
RESTORE trial, RBZ alone or combined with macular laser turned out to be superior
to laser alone, without significant differences between the 2 RBZ groups.
Compared to combined treatment (RBZ or triamcinolone associated with macular
laser) or photocoagulation laser alone (Diabetic Retinopathy Clinical Research
Network trial), RBZ with prompt or deferred laser was more effective than laser
alone at 1-year follow-up. At 3 years, prompt laser was not better than deferring
laser for 24 weeks or more. At 5 years, subjects treated with RBZ achieved better
long-term visual outcomes than patients managed with triamcinolone or laser
followed by very deferred RBZ. In conclusion, randomized clinical trials showed
that RBZ was superior to laser in DME treatment, providing excellent long-term
visual outcomes. Frequent injections were necessary in most of the patients to
properly control DME and maximize the visual benefits.
PMID- 28427067
TI - Intravitreal Aflibercept in Diabetic Macular Edema: Long-Term Outcomes.
AB - For decades, macular laser photocoagulation has been the standard of care in the
treatment of diabetic macular edema (DME). With the relatively recent advent of
anti-vascular endothelial growth factor (VEGF) agents, DME treatment has entered
a new era. VEGF is a well-known pro-angiogenic and pro-permeability factor
involved in the pathogenesis of DME. VEGF blockade has proven remarkably
effective at reducing DME and improving visual acuity (VA) in eyes with center
involved DME causing VA loss in several randomized controlled trials (RCTs).
Intravitreal aflibercept, ranibizumab, and bevacizumab (the latter used off
label) are 3 anti-VEGF molecules currently available for DME treatment.
Aflibercerpt is a 115-kDA recombinant fusion protein consisting of VEGF binding
domains of human VEGF receptors-1 and -2 fused to the Fc domain of human
immunoglobulin-G1. The ability to bind placental growth factors 1 and 2 (which is
another pro-permeability mediator) and a theoretically long half-life are
potential advantages of aflibercept over other anti-VEGF agents. The use of
intravitreal aflibercept in DME treatment has been investigated in several RCTs.
The aim of this chapter is to briefly report on the current evidence for treating
DME with intravitreal aflibercept.
PMID- 28427068
TI - Intravitreal Steroids in Diabetic Macular Edema.
AB - Over the past decade, great strides have been made in the management of diabetic
macular edema (DME). Therapeutic alternatives now include focal/grid laser
photocoagulation, vitreo-retinal surgery, and intraocular injection of anti
angiogenic and steroid molecules. Intravitreal administration of steroids
represents a fundamental alternative for recalcitrant and naive eyes with DME,
especially in those cases when anti-vascular endothelial growth factor (VEGF)
agents are contraindicated or a treatment regimen with fewer intravitreal
injections is required. Currently, 3 intravitreal corticosteroid options for DME
treatment are available: the dexamethasone delivery system, the fluocinolone
acetonide insert, and off-label intravitreal triamcinolone acetonide. All 3
agents are associated with risk of cataract progression and intraocular pressure
elevation, but they maintain a good safety profile. In patients who remain
unresponsive to anti-VEGF therapy, are pseudophakic, at low risk for glaucoma, or
who have significant cardiovascular risk, treatment with long-lasting intraocular
steroids is suggested. There still remain many unanswered questions about
intravitreal drugs, regarding dose, frequency, the correct regimen of each
treatment, and the potential long-term side effects.
PMID- 28427069
TI - Practical Lessons from Protocol I for the Management of Diabetic Macular Edema.
AB - Protocol I, a multicenter randomized clinical trial, compared the visual outcomes
of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or
deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser,
or sham injection with prompt laser for the treatment of center-involving
diabetic macular edema (DME). A total of 854 adult patients with type I or II
diabetes and any level of non-proliferative diabetic retinopathy or proliferative
retinopathy with adequate panretinal photocoagulation, with best-corrected visual
acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320)
and visual loss attributed to macular edema, or retinal thickening with central
subfield thickness of at least 250 um by OCT were enrolled. The main outcomes
relevant for practicing clinicians are as follows. (1) Intravitreal ranibizumab
treatment provides superior visual outcomes compared to conventional laser
treatment. (2) Adjunctive laser treatment does not appear to provide substantial
visual benefit compared to ranibizumab treatment alone, but may reduce the number
of injections required to resolve DME. Deferral of laser is likely beneficial in
patients with worse initial visual acuity. (3) Intravitreal triamcinolone
provides similar visual outcomes compared to intravitreal ranibizumab in
pseudophakic patients but is associated with a clinically important increased
risk of increased intraocular pressure (IOP), need for glaucoma medications, and
need for glaucoma surgery. (4) Delayed initiation of intravitreal ranibizumab
therapy provides improved visual outcome among patients initially treated with
conventional laser photocoagulation or triamcinolone, but the magnitude of the
benefit is not as great as is observed when ranibizumab treatment is initiated
promptly. (5) The number of ranibizumab injections required to achieve the
desired visual outcome decreases substantially after the first year, with the
majority of patients not requiring further treatment after 3 years. (6) Patients
who do not have a rapid response to ranibizumab still display long-term benefit
to continued therapy, although perhaps less than those with immediate
improvement. (7) Intravitreal ranibizumab is not only effective in reducing
retinal edema and improving BCVA among patients with DME, it is also a disease
modifying therapy and induces improvement of the diabetic retinopathy severity
score by 2 or more steps in approximately one third of patients. Triamcinolone
injection also induces improvement in diabetic retinopathy severity in DME
patients, but perhaps to a lesser degree. (8) No increased risk of systemic
adverse events was observed among patients treated with intravitreal ranibizumab
compared to sham-injected controls or triamcinolone-treated patients, but the low
frequency of adverse events, restrictive enrollment criteria, and specific
posology employed in this study limit the generalization of this conclusion to
patients routinely encountered in clinical practice. (9) There was no clinically
important increased risk of major ocular complications among patients treated
with intravitreal ranibizumab (including the risk of glaucoma), although
endophthalmitis is a potentially devastating outcome should it occur. In addition
to the risk of endophthalmitis, intravitreal triamcinolone injection was
associated with clinically important increased risk of cataract progression and
increased IOP.
PMID- 28427070
TI - Practical Lessons from Protocol T for the Management of Diabetic Macular Edema.
AB - PURPOSE: To review the results of Diabetic Retinopathy Clinical Research Network
Protocol T, as applied to clinical practice. METHODS: Review of major
publications reporting the results of Protocol T, a randomized single-masked (in
year-1 only), multicenter clinical trial comparing aflibercept, bevacizumab, and
ranibizumab as treatment option for center-involving diabetic macular edema
(DME). The main outcome measures were change in visual acuity (VA), central
subfield thickness (CST) on optical coherence tomography, cost effectiveness,
burden of care, and safety. RESULTS: A total of 660 participants (mean age 61 +/-
10 years, 47% women, 65% Caucasian) were randomized to treatment with aflibercept
(n = 224), ranibizumab (n = 218), or bevacizumab (n = 218). The majority of
patients (90%) had type II diabetes, with an average duration of 17 +/- 11 years.
About half the patients had baseline ETDRS VA of 20/32 to 20/40, and half had
ETDRS VA of 20/50 to 20/320 in all 3 cohorts. Patients in all 3 cohorts received
a similar number of injections during the study period (9-10 in year-1; 5-6 in
year-2). The year-1 improvement in ETDRS letters was significantly higher for
aflibercept than for ranibizumab and bevacizumab in patients with baseline VA
20/50 or worse (p = 0.003 and p < 0.001, respectively), but was no different in
patients with better baseline VA of 20/32 to 20/40 (p = 0.69). By year-2, among
patients with poorer baseline VA, there was a difference in mean letters gained
between aflibercept and bevacizumab (p = 0.02), but no difference between
aflibercept and ranibizumab (p = 0.18). At year-2, there was no clinically
meaningful difference in VA improvement (i.e., gain or loss of >=10 or >=15
letters) among any of the agents (p > 0.74). Bevacizumab was less effective than
the other agents in decreasing CST at years-1 and -2 in the overall cohort of
patients (p < 0.001). However, bevacizumab is substantially cheaper and much more
cost-effective (when comparing expense and quality of life measures) than
aflibercept and ranibizumab. The cost of other agents would have to decrease by
80-90% to be cost-effective relative to bevacizumab. Intravitreal administration
of anti-VEGF therapy has relatively few ocular and systemic side effects, but
caution may be warranted for patients with a recent history or high risk of
myocardial infarction or stroke. CONCLUSIONS: Aflibercept, bevacizumab, and
ranibizumab are highly effective treatments for DME. Bevacizumab is more cost
effective than aflibercept and ranibizumab. Intravitreal administration of drugs
is relatively safe; however, intravitreal administration may be associated with
severe systemic side effects in a small percentage of patients, particularly in
those with a prior history of or high risk of Anti-Platelet Trialists'
Collaboration events.
PMID- 28427071
TI - Is Laser Still Important in Diabetic Macular Edema as Primary or Deferral
Therapy?
AB - Laser treatment was used in the past to reduce the visual loss due to diabetic
macular edema. The recent advent of anti-vascular endothelial growth factor (anti
VEGF) has completely revolutionized the management of diabetic retinopathy, with
a significant improvement in the overall prognosis. Nevertheless, macular laser
can still be applied in selected cases characterized by retinal thickness <=400
microns, high visual acuity, extrafoveal location, and contraindications to the
intravitreal approach with anti-VEGF and steroids. In addition, the combined
therapy with anti-VEGF and macular laser can exploit the synergistic effects of
both therapies, leading to a simpler and more practical management of patients
over the long-term follow-up.
PMID- 28427072
TI - Anti-Vascular Endothelial Growth Factor Injections: The New Standard of Care in
Proliferative Diabetic Retinopathy?
AB - For decades, panretinal photocoagulation (PRP) has been the standard of care for
the treatment of proliferative diabetic retinopathy (PDR). The relatively recent
advent of anti-vascular endothelial growth factor (VEGF) formulations for
intravitreal injection has provided a fresh perspective on PDR treatment,
especially in eyes with concurrent diabetic macular edema (DME). The anti-VEGF
agent ranibizumab has demonstrated a potentially protective effect on eyes with
DME in terms of progression to PDR in the RIDE/RISE trials, as has aflibercept in
the VIVID/VISTA trials. In 2015, these 2 agents were approved by the Food and
Drug Administration for the treatment of PDR with DME, though PRP still remains
the standard of care for eyes without baseline DME. Published results from
Protocol S illustrate the non-inferiority of ranibizumab versus PRP in the
treatment of PDR, the first prospective study to do so in eyes with and without
baseline DME. These results also reveal that treatment with ranibizumab, when
compared to standard treatment with PRP, may also lead to less peripheral visual
field loss, reduced need for vitrectomy, and reduced chance for developing DME.
Both PRP and intravitreal ranibizumab have very low rates of adverse events.
However, treatment with anti-VEGF agents generally is associated with higher
costs, increased need for follow-up, and the risk of potentially catastrophic
ocular complications (e.g., endophthalmitis) and systemic side effects. Anti-VEGF
agents should be considered in cases of media opacity preventing completion of
PRP in compliant patients without recent cerebrovascular accident or myocardial
infarction, though the long-term efficacy of these agents remains to be studied,
especially after the discontinuation of injections.
PMID- 28427073
TI - Surgical Management and Techniques.
AB - Technical advancements have substantially extended the indications for surgery in
diabetic retinopathy (DR) during the last 40 years, from the traditional
indications including non-clearing vitreous hemorrhage, traction retinal
detachment (RD), and traction-rhegmatogenous RD, to epiretinal membrane (ERM),
vitreomacular traction, diffuse macular edema, neovascular glaucoma, and anterior
hyaloid fibrovascular proliferation. The goals of vitreoretinal surgery in DR are
multiple: clearing media opacities, release of traction (anteroposterior and/or
tangential), segmentation and/or removal of traction bands, peeling of ERMs,
hemostasis, laser photocoagulation, and tamponade of retinal breaks with gas or
silicone oil. The best management is achieved with integrated care provided by
physicians with expertise in medical management of diabetes and surgical care of
DR. In this chapter, the indications for surgery, preoperative considerations,
surgical techniques, and complications, together with their management, will be
discussed.
PMID- 28427074
TI - Enzymatic Vitreolysis for Vitreomacular Traction in Diabetic Retinopathy.
AB - Vitreomacular traction (VMT) is one of many possible factors involved in the
etiology of diabetic macular edema (DME). Pharmacologic vitreoretinal separation
is a potential alternative to vitrectomy for VMT in diabetic retinopathy. Small
case series have been published on the use of enzymatic vitreolysis in tractional
DME, and demonstrate that the enzymatic release of the posterior vitreous cortex
is more likely following the injection of plasmin enzyme. Further prospective and
randomized clinical trials are necessary to evaluate the clinical relevance of
ocriplasmin for vitreomacular traction in diabetic retinopathy, and additional
studies are needed to determine more accurately which patients might benefit most
from this treatment and how often and at what concentration ocriplasmin should be
administered.
PMID- 28427075
TI - Diabetic Macular Edema: Emerging Strategies and Treatment Algorithms.
AB - Diabetic macular edema (DME) is the most common cause of vision loss in diabetic
patients, and its management is often a long process requiring frequent
monitoring and therapeutic interventions. During the past several decades,
numerous treatments have been developed for the treatment of DME. Although many
of them have been found to be effective and safe, there is relatively little
comparative data, and no established guidelines for the optimal treatment
approach exist. In this chapter, the evolution of DME therapies is reviewed, and
the current common practice patterns are discussed. Available data from clinical
trials on the commonly used agents, as well as comparative studies and
combination therapies are reviewed. Additionally, recent advances and novel
treatment options that are currently being investigated are also discussed.
PMID- 28427076
TI - Application of Clinical Trial Results to Clinical Practice.
AB - Two critical questions one must answer as one applies the results of a clinical
trial to clinical practice are: (1) Regardless of whether the trial result is
likely to be replicated or reproduced in a second large-scale trial, are the
results likely to be reproduced in one's practice? (2) Regardless of whether the
experimental treatment was better than the alternative on average for a
population of patients, are the results clinically important for a given patient
in one's practice? To determine if a study result is likely to be reproduced in
one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps
been taken to minimize bias? (2) Is the result likely due to the treatment? (3)
Is the result unlikely due to chance? (4) Is the study population representative
of one's patients? (5) Is the totality of evidence consistent? If the answer to
all 5 questions is "yes," then we posit that the trial result is likely to be
reproduced in one's practice. If not, the likelihood of reproducibility is low.
If the answer is yes to all questions except the last, then reproducibility in
one's practice is not clear and depends on the strength of the prior versus the
current evidence. If the prior evidence is strong, such as multiple pivotal
randomized clinical trials, and if the current trial result is not consistent
with the previous studies, then the current result may not be reproduced in one's
practice. To determine if a study result is clinically important, a 3-step
approach is suggested. Step 1. Decide, a priori, what a clinically meaningful
difference between 2 treatments would be. This choice defines regions of
beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence
intervals (CIs). Determine whether the 95% CI mostly includes the range of
clinically beneficial outcomes and lies outside the range of clinically harmful
outcomes. If these conditions are met, the result is probably clinically
important, but the result may or may not be statistically significant. Put the
CIs and the regions of benefit/harm together to make a decision about clinically
important effects. Step 3. Assess the proportion of eyes with clinically
meaningful changes in vision. The proportion of "responders" among patients
receiving a given treatment reflects the likelihood of one's patient having a
clinically meaningful response to the treatment. In summary, not all
statistically significant results are reproduced, even those of carefully
designed clinical trials. Determining if a study result is likely to be
reproduced in one's practice is even more problematic. The 5-question test may
help in this regard. The 5-question test attempts to assess whether steps have
been taken to: minimize bias; avoid confounding; ensure adequate statistical
power to support precision in the estimates of population parameters; insure
external validity of the trial result; and determine whether there is a
convergence of evidence consistent with the trial's major findings. To determine
if a statistically significant result is likely to be clinically important, a 3
step approach may be useful, focusing on CIs and the proportion of eyes with
clinically meaningful changes in vision. Application of clinical trial results to
clinical practice requires critical analysis of the extant literature and good
clinical judgment.
PMID- 28427078
TI - A Case of Adult Metastatic Rhabdomyosarcoma of the Prostate Cured by Long-Term
Chemotherapy with Local Radiation.
AB - A 32-year-old man visited our hospital due to urinary retention. Prostate
specific antigen was 13.7 ng/mL. Imaging examinations showed a large prostatic
tumor and lung and internal iliac lymph node metastases. Transrectal biopsy
confirmed embryonal rhabdomyosarcoma of the prostate classified as cT2bN1M1
(stage IV) by the International Rhabdomyosarcoma Study (IRS) Group staging
system. Systemic chemotherapy was started according to the IRS III regimen 36,
which consisted of 16 weeks of induction chemotherapy with radiation. After 20
weeks, magnetic resonance imaging showed the disappearance of metastases, and the
prostate tumor shrunk markedly. Moreover, prostatic re-biopsy showed no viable
tumor cells. Maintenance chemotherapy, excluding vincristine because of severe
peripheral nerve disorder, was performed for 2 years. There has been no
recurrence for 49 months after the termination of maintenance chemotherapy. To
the best of our knowledge, this is the longest surviving case of adult-onset
metastatic rhabdomyosarcoma of the prostate reported in the literature.
PMID- 28427077
TI - MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in
Gallbladder Cancer.
AB - BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary
tract malignancy, with extremely poor prognosis. In the present study, we
analyzed the potential involvement of MYBL2, a member of the Myb transcription
factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression
levels were measured in GBC and cholecystitis tissue specimens using quantitative
real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of
MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting
Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU)
retention assay, flow cytometry analysis, western blot, and a xenograft model of
GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues
and associated with histological differentiation, tumour invasion, clinical stage
and unfavourable overall survival in GBC patients. The downregulation of MYBL2
expression resulted in the inhibition of GBC cell proliferation, and DNA
replication in vitro, and the growth of xenografted tumours in nude mice.
Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS:
MYBL2 overexpression promotes GBC cell proliferation through the regulation of
the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a
potential prognostic and therapeutic biomarker in GBC patients.
PMID- 28427079
TI - Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural
Effusion: An Updated Meta-Analysis.
AB - BACKGROUND: The role of combinations of tumor markers such as carcinoembryonic
antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a
fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has
not been clearly established. OBJECTIVES: This meta-analysis was performed to
establish the overall diagnostic accuracies of combinations of these pleural
fluid tumor markers for MPE. METHODS: The PubMed, Ovid, Embase, Web of Science,
and Cochrane bibliographic databases were searched. Sensitivity, specificity, and
other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3,
CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic
review of English-language studies. RESULTS: Twenty studies met the inclusion
criteria. For pleural fluid tumor marker combinations including more than 3
studies, the summary estimates of the sensitivity/specificity for diagnosing MPE
were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19
9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94.
CONCLUSIONS: In patients with undiagnosed pleural effusion, the combinations of
positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for
pleural malignancy, but the sensitivity of these tests is poor. Therefore, their
routine role in the diagnostic algorithm of these patients is questionable, and
management decisions should depend on positive cytological or biopsy results from
the pleura.
PMID- 28427080
TI - Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a
Stimulated Condition of Immunoglobulin A Nephropathy.
AB - : Backgroud/Aims: The aim of this study was to investigate the potential
renoprotective effect of rapamycin on the autophagy of podocytes treated with the
supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from
immunoglobulin A nephropathy (IgAN) patients. METHODS: Monomeric IgA1 (mIgA1) was
isolated from the serum of IgAN patients or healthy volunteers, and then
transformed to aIgA1 by heating. Subsequently, the aIgA1-mesangial cell
supernatant was prepared by collecting the medium of mouse mesangial cells
(MSC1097) cultured with aIgA1 (100 mg/L) from different IgAN patients or healthy
volunteers for 48 h. Subsequently mouse podocytes (MPC5) were exposed to the
supernatant of the aIgA1-mesangial cells for 24 h, using 100 mg/L aIgA1 from
healthy volunteers as the control group or 100 mg/L aIgA1 from IgAN patients as
the IgANs group, in RPMI 1640 medium. The MPC5 cells in the IgANs+Rap group were
cultured with rapamycin (10 nmol/L) and the supernatant of MSC-1097 cells
cultured with aIgA1 from IgAN patients in RPMI 1640 medium. Autophagy was
assessed by western blot analysis (LC3, p62), electron microscopy, and
immunofluorescence staining (LC3, p62, and CD63). The apoptosis of podocytes was
evaluated by flow cytometry, and the expression of apoptosis-associated proteins
cleaved-caspase-3 and caspase-3 were determined by western blot analysis.
RESULTS: Deficient autophagy, which was evident by decreased LC3-II and CD63
levels, caused accumulation of p62, and fewer autophagosomes were observed in the
MPC5 cells cultured with the IgAN supernatant, along with stronger expression of
cleaved caspase-3 and a higher apoptosis rate. Inhibition of autophagy was
alleviated in the IgANs+Rap group. The LC3-II/LC3-I ratio increased by almost
30%, the accumulated p62 amount was reduced by 50%, and the number of
autophagosomes per podocyte increased to about 7 times that of the IgAN groups.
These results were confirmed by immunofluorescence staining. In addition, the
apoptosis rate of MPC5 cells decreased from 19.88% in the IgAN group to 16.78% in
the IgANs+Rap group, which was accompanied by a weaker expression level of
cleaved caspase-3. CONCLUSIONS: Rapamycin can reduce the apoptosis of podocytes
by inducing autophagy in IgAN.
PMID- 28427081
TI - Choroidal Thickness and Microperimetry Sensitivity in Age-Related Macular
Degeneration.
AB - PURPOSE: To assess choroidal thickness (CT) and its relationship to retinal
sensitivity in mild/moderate age-related macular degeneration (AMD). METHODS:
Seventy-two eyes of 51 participants with mild/moderate AMD and 36 eyes of 18 age
matched normal participants were prospectively recruited to undergo enhanced
depth imaging optical coherence tomography (EDI-OCT) imaging and microperimetry
(MP) functional assessment. OCT-measured CT and retinal thickness (RT) were
matched with MP sensitivity at 13 retinal loci, and correlations were analysed.
RESULTS: Patients with AMD had an average RT 56.5 MUm greater than those without
AMD (p < 0.001). There was no significant difference in CT between normal and AMD
participants (p = 0.36). In patients without atrophy or pigment epithelial
detachment, there was no correlation between MP sensitivity and CT (p = 0.08);
however, a correlation between RT and MP was detected (b = 0.006, p = 0.046).
Among patients without AMD, MP sensitivity was positively correlated with RT (b =
0.007, p < 0.001) and negatively correlated with CT (b = 0.0046, p = 0.035).
CONCLUSIONS: CT does not correlate with retinal sensitivity in AMD. Although
choroidal damage and impaired choroidal perfusion appear to be important concepts
in AMD pathogenesis, increasing choroidal thinning may not be associated with
worsening retinal function in AMD.
PMID- 28427082
TI - Perioperative Outcomes and Safety of Atrial Fibrillation Catheter Ablation in
Octogenarians: A Retrospective Study and Review of the Benefits of Rhythm
Control.
AB - OBJECTIVES: Catheter ablation for rhythm control has emerged as a successful
therapeutic option for the treatment of atrial fibrillation (AF), though it has
not been well studied in octogenarians. This study evaluates its safety in
octogenarians in a community hospital and reviews the benefits of rhythm control.
METHODS: Among 1,592 patients undergoing AF ablation, 84 octogenarian were
identified. The primary outcome was normal sinus rhythm (NSR) on
electrocardiogram at discharge. Secondary outcomes were periprocedural
complications and markers and risks of reablation compared to younger cohorts.
RESULTS: An NSR on discharge occurred in 83 patients. Three patients required
pacing for symptomatic sinus bradycardia, complete heart block, and symptomatic
junctional bradycardia, respectively. Reablation for recurrent AF occurred in 23
octogenarians. Using the octogenarians as reference, the relative risk (RR) of 1
reablation was not significantly different among the age groups 70-79, 60-69, and
<60 years. The RR of 2 reablations was greater in the octogenarian group (RR 0.26
[95% CI 0.09-0.71, p = 0.008], 0.42 [95% CI 0.17-1.04, p = 0.06], and 0.27 [95%
CI 0.1-0.75, p = 0.01], respectively). Coronary artery disease (OR 0.14, 95% CI
0.02-0.68, p = 0.026) and percutaneous coronary intervention (OR 0.13, 95% CI
0.02-0.63, p = 0.021) were markers for reablation. CONCLUSION: AF catheter
ablation achieved an NSR with minimal periprocedural complications. The benefits
of rhythm control should be considered in treatment.
PMID- 28427083
TI - Cumulative risk of breast cancer screening outcomes according to the presence of
previous benign breast disease and family history of breast cancer: supporting
personalised screening.
AB - BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening
results, screen-detected cancer, and interval breast cancer in mammography
screening among women with and without a previous benign breast disease and a
family history of breast cancer. METHODS: The cohort included 42 928 women first
screened at the age of 50-51 years at three areas of the Spanish Screening
Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and
followed up until December 2012. We used discrete-time survival models to
estimate the cumulative risk of each screening outcome over 10 biennial screening
exams. RESULTS: The cumulative risk of false-positive results, screen-detected
breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a
previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family
history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous
benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women
without either of these antecedents, respectively. CONCLUSIONS: Women with a
benign breast disease or a family history of breast cancer had an increased
cumulative risk of favourable and unfavourable screening outcomes than women
without these characteristics. A family history of breast cancer did not increase
the cumulative risk of false-positive results. Identifying different risk
profiles among screening participants provides useful information to stratify
women according to their individualised risk when personalised screening
strategies are discussed.
PMID- 28427084
TI - Long-term improvement of breast cancer survivors' quality of life by a 2-week
group physical and educational intervention: 5-year update of the 'PACThe' trial.
AB - BACKGROUND: The advantages of adapted physical activity and nutritional education
(APANE) on breast cancer prognosis and quality of life (QoL) are well known, but
long-term results are lacking. METHODS: A randomised controlled trial testing a 2
week intervention in hydrothermal centres including APANE enrolled 251 patients
post-chemotherapy. QoL and weight control were significantly improved at 12
months. A 5-year follow-up was performed to evaluate the persistence of
improvements. RESULTS: QoL increase (SF36) was persistent: effect-size at 2, 3, 4
and 5 years equalled respectively 0.27 (-0.01; 0.56), 0.28 (-0.02; 0.58), 0.41
(0.02; 0.81) and 0.45 (0.11; 0.80). Weight control observed after intervention
lasted 2 years: 2.7% decrease at 1 year (P=0.0085), 2.5% at 2 years (P=0.025);
and respectively for waist -2.4% (-3.6; -1.1) (P=0.000014) and -1.3% (-2.5; -0.1)
(P=0.0072). CONCLUSIONS: A 2-week intervention in hydrothermal centres performed
shortly after chemotherapy can durably improve breast cancer patients' QoL and
reduce weight.
PMID- 28427085
TI - Tumour invasiveness, the local and systemic environment and the basis of staging
systems in colorectal cancer.
AB - BACKGROUND: The present study aimed to examine the relationship between tumour
invasiveness (T stage), the local and systemic environment and cancer-specific
survival (CSS) of patients with primary operable colorectal cancer. METHODS: The
tumour microenvironment was examined using measures of the inflammatory
infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma
percentage (TSP) and tumour budding. The systemic inflammatory environment was
examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte
ratio (NLR). A 5-year CSS was examined. RESULTS: A total of 331 patients were
included. Increasing T stage was associated with colonic primary, N stage, poor
differentiation, margin involvement and venous invasion (P<0.05). T stage was
significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP
(P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In
patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas
Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%,
respectively. The Glasgow Microenvironment Score, a score based on KM grade and
TSP, stratified survival from 93 to 58%. CONCLUSIONS: Although associated with
increasing T stage, local and systemic tumour environment characteristics, and in
particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants
of survival and may be utilised in the staging of patients with primary operable
colorectal cancer.
PMID- 28427086
TI - Self-sampling to improve cervical cancer screening coverage in Switzerland: a
randomised controlled trial.
AB - BACKGROUND: The aim of this study is to evaluate whether self-sampling can
increase screening attendance of women who do not attend regular screening in
Switzerland. METHODS: Participants were proactively recruited in Geneva between
September 2011 and November 2015. Women (25-69 years) who had not undergone CC
screening in the last 3 years were considered eligible. Through a 1 : 1 ratio
randomisation, enrolled participants were invited to either undergo liquid-based
cytology, which was performed by a health-care provider (control group, CG) or to
take a self-sample for HPV-testing, which was mailed to their home (intervention
group, IG). RESULTS: A total of 331 and 336 women were randomised in the CG and
in the IG, respectively. Overall, 7.3% (95% CI: 4.9-10.6) women in the CG and
5.7% (95% CI: 3.6-8.7) women in the IG did not undergo the initial screening
(P=0.400). There were 1.95% (95% CI: 0.8-4.3) women in the CG and 5.05% (95% CI:
3.1-8.1) women in the IG with a positive screen who did not attend triage and
colposcopy (P=0.036). CONCLUSIONS: The participation in CC screening in women
offered self-sampling was not higher than among those offered specimen collection
by a clinician. Compliance with further follow-up for women with a positive HPV
test on the self-sample requires further attention.
PMID- 28427087
TI - Pretreatment serum uracil concentration as a predictor of severe and fatal
fluoropyrimidine-associated toxicity.
AB - BACKGROUND: We investigated the predictive value of dihydropyrimidine
dehydrogenase (DPD) phenotype, measured as pretreatment serum uracil and
dihydrouracil concentrations, for severe as well as fatal fluoropyrimidine
associated toxicity in 550 patients treated previously with fluoropyrimidines
during a prospective multicenter study. METHODS: Pretreatment serum
concentrations of uracil and dihydrouracil were measured using a validated LC
MS/MS method. The primary endpoint of this analysis was global (any) severe
fluoropyrimidine-associated toxicity, that is, grade ?3 toxicity according to the
NCI CTC-AE v3.0, occurring during the first cycle of treatment. The predictive
value of uracil and the uracil/dihydrouracil ratio for early severe
fluoropyrimidine-associated toxicity were compared. Pharmacogenetic variants in
DPYD (c.2846A>T, c.1679T>G, c.1129-5923C>G, and c.1601G>A) and TYMS (TYMS 5'-UTR
VNTR and TYMS 3'-UTR 6-bp ins/del) were measured and tested for associations with
severe fluoropyrimidine-associated toxicity to compare predictive value with DPD
phenotype. The Benjamini-Hochberg false discovery rate method was used to control
for type I errors at level q<0.050 (corresponding to P<0.010). RESULTS: Uracil
was superior to the dihydrouracil/uracil ratio as a predictor of severe toxicity.
High pretreatment uracil concentrations (>16 ng ml-1) were strongly associated
with global severe toxicity (OR 5.3, P=0.009), severe gastrointestinal toxicity
(OR 33.7, P<0.0001), toxicity-related hospitalisation (OR 16.9, P<0.0001), as
well as fatal treatment-related toxicity (OR 44.8, P=0.001). None of the DPYD
variants alone, or TYMS variants alone, were associated with severe toxicity.
CONCLUSIONS: High pretreatment uracil concentration was strongly predictive of
severe, including fatal, fluoropyrimidine-associated toxicity, and is a highly
promising phenotypic marker to identify patients at risk of severe
fluoropyrimidine-associated toxicity.
PMID- 28427089
TI - Editor's Highlight: Exposure to CrVI during Early Pregnancy Increases Oxidative
Stress and Disrupts the Expression of Antioxidant Proteins in Placental
Compartments.
AB - Epidemiologic studies document relationships between chromium VI (CrVI) exposure
and increased risk of spontaneous abortion, stillbirth, preterm birth, and
neonatal death in pregnant women. Environmental contamination with CrVI is a
growing problem both in the United States and developing countries. CrVI is
widely used in numerous industries. This study was designed to understand the
mechanism of CrVI toxicity on placental oxidative stress and antioxidant (AOX)
machinery. Pregnant mother rats were treated with or without CrVI (50 ppm
K2Cr2O7) through drinking water from gestational day (GD) 9.5-14.5, and placentas
were analyzed on GD 18.5. Results indicated that CrVI reduced the trophoblast
cell population. CrVI increased reactive oxygen species (ROS) and decreased the
expression of AOX proteins. CrVI disrupts the trophoblast proliferation of the
placenta. This study provides insight into the critical role of AOXs in placental
function.
PMID- 28427088
TI - A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with
MGMT promoter methylation.
AB - BACKGROUND: Presently, few options are available for refractory colorectal cancer
(CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a
frequent and early event in CRC tumourigenesis. This epigenetic silencing is a
predictor of response to the alkylating drug temozolomide in glioblastoma.
Preclinical evidences and some case reports showed temozolomide activity in CRC
with MGMT silencing, but the available data from clinical trials are
inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according
to a two-stage Simon's optimal design to investigate activity and safety of
temozolomide in refractory CRC harbouring MGMT promoter methylation. The primary
end point was overall response rate (ORR). Patients who failed two or more prior
treatments received temozolomide at a dose of 150-200 mg m-2 per day on days 1-5
every 28 days. RESULTS: From July 2012 to June 2016, 225 patients were screened,
80 showed MGMT promoter methylation and 41 were enrolled. Overall response rate
was 10% and disease control rate was 32%. Median progression-free survival and
overall survival were 1.9 and 5.1 months, respectively. CONCLUSIONS: Temozolomide
showed a modest activity in this heavily pretreated population and the study did
not meet its primary end point. The role of temozolomide in CRC remains still
controversial and further research is warranted.
PMID- 28427090
TI - The Aldosterone Synthase Inhibitor FAD286 is Suitable for Lowering Aldosterone
Levels in ZDF Rats but not in db/db Mice.
AB - Inhibition of aldosterone synthase is an alternative treatment option to
mineralocorticoid receptor antagonism to prevent harmful aldosterone actions.
FAD286 is one of the best characterized aldosterone synthase inhibitors to date.
FAD286 improves glucose tolerance and increases glucose-stimulated insulin
secretion in obese and diabetic ZDF rats. However, there is limited knowledge
about the dose-dependent effects of FAD286 on plasma aldosterone, corticosterone,
and 11-deoxycorticosterone in ZDF rats and in db/db mice, a second important
rodent model of obesity and type 2 diabetes. In addition, effects of FAD286 on
plasma steroids in mice and rats are controversial. Therefore, obese Zucker
diabetic fatty (ZDF) rats and db/db mice were treated with FAD286 for up to 15
weeks and plasma steroids were evaluated using highly sensitive liquid
chromatography-tandem mass spectrometry. In ZDF rats, FAD286 (10 mg/kg/d)
treatment resulted in nearly complete disappearance of plasma aldosterone while
corticosterone levels remained unaffected and those of 11-deoxycorticosterone
were increased ~4-fold compared to vehicle control. A lower dose of FAD286 (3
mg/kg/d) showed no effect on plasma aldosterone or corticosterone, but 11
deoxycorticosterone was again increased ~4-fold compared to control. In contrast
to ZDF rats, a high dose of FAD286 (40 mg/kg/d) did not affect plasma aldosterone
levels in db/db mice although 11-deoxycorticosterone increased ~2.5-fold. A low
dose of FAD286 (10 mg/kg/d) increased plasma aldosterone without affecting
corticosterone or 11-deoxycorticosterone. In conclusion, the aldosterone synthase
inhibitor, FAD286, lowers plasma aldosterone in obese ZDF rats, but not in obese
db/db mice.
PMID- 28427091
TI - [Development and Evaluation of herzwegweiser.de - An Informational Website
designed for Post-Rehabilitation Support of Cardiac Patients and their Healthcare
Professionals in Berlin-Brandenburg].
AB - The internet portal 'herzwegweiser.de' was developed to assist individuals with
cardiovascular diseases in the phase III rehabilitation in the region of Berlin
Brandenburg. It provides information on this specific disease as well as on
aftercare services, e. g. regional cardiac groups. For the medical and
therapeutic colleagues specific information such as treatment guidelines and a
cardiac group placement service for trainers and medical doctors were set up. The
study was based on a mixed-methods design. Initially, structured interviews were
conducted to identify the expectations and needs of the internet portal. After
implementation of the portal, a partially standardized written survey was used to
evaluate its acceptance and usability. 105 former rehab patients and 42 medical
colleagues participated. The evaluation of the questionnaires was carried out
with frequency distributions, mean comparisons and Chi-square tests. The site was
rated with an overall high approval rating. Over 90% of the former rehab patients
rated content, structure, design, and the search function of the portal positive
as did more than 85% of the medical colleagues. 97% of the former rehab patients
and 95% professionals would recommend 'herzwegweiser.de'. This internet portal
can serve as a model for other regions and possibly other diseases.
PMID- 28427092
TI - Erratum: Pulmonary Embolism and Atrial Fibrillation: Two Sides of the Same Coin?
A Systematic Review.
PMID- 28427093
TI - Video-Assisted Thoracic Surgical Right Upper Lobectomy with Bronchus-First and
Simultaneous Vessel Stapling Technique.
AB - A method of video-assisted thoracic surgical (VATS) right upper lobectomy with
bronchus-first and simultaneous vessel stapling will be introduced. In this
study, all cases underwent two-port VATS as follows: first, the right upper lobe
bronchus was identified and stapled; then, all right upper lobe vessels were
stapled simultaneously. This method was performed in 50 cases. There was no
surgical mortality, hemorrhage, vascular injuries, or conversion. This technique
can reduce wound size and operative time and make the operation safer and easier
to accomplish.
PMID- 28427094
TI - Statin Therapy in Patients Undergoing Coronary Artery Bypass Grafting for Acute
Coronary Syndrome.
AB - BACKGROUND: This study evaluates whether preoperative statin therapy improves
clinical outcomes in patients referred to coronary artery bypass grafting (CABG)
for acute coronary syndrome (ACS). METHODS: A total of 1,151 patients undergoing
CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical
myocardial infarction registry and subdivided into two groups according to their
preoperative statin status (statin naive vs. statin group). A logistic regression
model was employed to analyze the impact of a statin therapy and dose for the
endpoints in-hospital mortality and major adverse cardiac events (MACE). RESULTS:
Demographics, pre- and intraoperative data of the statin-naive group (n = 208;
18%) and statin-treated group (n = 943, 82%) did not differ. In-hospital
mortality (12.6 vs. 6.3%, p = 0.002) and MACE rates (22.1 vs. 9.7%, p < 0.001)
were significantly higher in statin naive when compared with statin-treated
patients with ACS, respectively. Mevalonic acid revealed that both low- and high
dose statin treatment was associated to a reduction in in-hospital mortality and
MACE, without a dose-dependent statin effect. CONCLUSION: Statin therapy in
patients with ACS undergoing CABG reduces in a dose-independent manner in
hospital mortality and MACE.
PMID- 28427095
TI - Performance of Endocarditis-Specific Risk Scores in Surgery for Infective
Endocarditis.
AB - BACKGROUND: Risk models can play an important part in the decision-making of
surgery for infective endocarditis, but they remain underutilized. Several
endocarditis-specific risk models have been recently published with the aim to
improve on existing general cardiac surgery scores such as EuroSCORE. We compared
their prognostic utility of mortality and morbidities for infective endocarditis
surgery. METHODS: The additive Society of Thoracic Surgeon's (STS) Endocarditis
score, Costa score, De Feo-Cotrufo score, and Pulsuse score were calculated for
consecutive patients undergoing cardiac surgery for active infective endocarditis
during 2005 to 2011 at Auckland City Hospital and their discriminative value for
adverse outcomes assessed. RESULTS: Mean scores for 146 endocarditis surgery
patients with operative mortality 6.8% (10) were additive STS score: 32.2 +/-
13.5, Costa score: 12.0 +/- 6.8, De Feo-Cotrufo score: 14.6 +/- 9.2, and Pulsuse
score 2.2 +/- 1.3. Areas under curve and 95% confidence intervals for operative
mortality were 0.699 (0.534-0.865), 0.596 (0.426-0.765), 0.744 (0.590-0.899), and
0.673 (0.510-0.836), respectively. All four scores could also discriminate
mortality during follow-up and composite morbidity, with the De Feo-Cotrufo score
having the best overall performance. CONCLUSION: Endocarditis-specific risk
models had moderate discrimination of operative mortality and most postoperative
complications, and the De Feo-Cotrufo score is the preferred score to advise
clinical decisions in this setting.
PMID- 28427096
TI - PDE 2015: cAMP Signaling, Protein Kinase A (PKA) and Phosphodiesterases (PDEs):
How Genetics Changed the Way We Look at One of the Most Studied Signaling
Pathways.
PMID- 28427097
TI - Systematic Quantification of GPCR/cAMP-Controlled Protein Kinase A Interactions.
AB - The diffusible second messenger cyclic AMP (cAMP) originates from multiple G
protein-coupled receptor (GPCR) cascades activating the intracellular key
effector protein kinase A (PKA). Spatially and temporally restricted cAMP-fluxes
are directly sensed by macromolecular PKA complexes. The consequences are
alterations of molecular interactions, which lead to activation of
compartmentalized PKA phosphotransferase activities, regulating a vast array of
cellular functions. To decode cell-type and cell-compartment specific PKA
functions, the spatio-temporal dynamics of small molecule:protein interactions,
protein:protein interactions (PPIs), cAMP-mobilization, and phosphotransferase
activities need to be determined directly in the appropriate cellular context. A
collection of cell-based reporters has been developed to either visualize or
quantitatively measure kinase activities or PKA complex formation/dissociation.
In this review, we list a collection of unimolecular and bimolecular PKA
biosensors, followed by the specification of the modular design of a Renilla
luciferase based protein-fragment complementation assay (PCA) platform for
measuring PKA network interactions. We discuss the application spectrum of the
PCA reporter to identify, quantify, and dissect dynamic and transient PKA
complexes downstream of specific GPCR activities. We specify the implementation
of a PCA PKA platform to systematically quantify the concurrent involvement of
receptor-cAMP signaling, post-translational modifications, and kinase subunit
mutations/perturbations in PKA activation. The systematic quantification of
transient PKA network interactions will contribute to a better understanding how
GPCR-recognized input signals are streamlined through the compartmentalized and
cAMP-interacting PKA signalosome.
PMID- 28427098
TI - OPA1 in Lipid Metabolism: Function of OPA1 in Lipolysis and Thermogenesis of
Adipocytes.
AB - OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of
mitochondria. It was recently also shown to locate on lipid droplets in
adipocytes where it functions as an A-kinase anchoring protein (AKAP) that
mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of
perilipin (Plin1). In brown adipocytes indirect evidence support the notion that
OPA1 regulation of fission serves to increase thermogenesis, which thereby
contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid
droplets serves as a gatekeeper to control lipolysis induced by adrenergic
agonists. However, the function of OPA1 in lipolysis and thermogenesis in
inducible brown adipocytes (brite/beige cells) remains elusive. Here we discuss
the role of OPA1 in lipid metabolism.
PMID- 28427099
TI - Role of Phosphodiesterases on the Function of Aryl Hydrocarbon Receptor
Interacting Protein (AIP) in the Pituitary Gland and on the Evaluation of AIP
Gene Variants.
AB - Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by
loss-of-function germline mutations in the AIP gene. Patients harboring AIP
mutations usually present with somatotropinomas resulting either in gigantism or
young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor
suppressor properties in somatotroph cells. Among other mechanisms proposed to
explain this function, a regulatory effect over the 3',5'-cyclic adenosine
monophosphate (cAMP) signaling pathway seems to play a prominent role. In this
setting, the well-known interaction between AIP and 2 different isoforms of
phosphodiesterases (PDEs), PDE2A3 and PDE4A5, is of particular interest. While
the interaction with over-expressed AIP does not seem to affect PDE2A3 function,
the reported effect on PDE4A5 is, in contrast, reduced enzymatic activity. In
this review, we explore the possible implications of these molecular interactions
for the function of somatotroph cells. In particular, we discuss how both PDEs
and AIP could act as negative regulators of the cAMP pathway in the pituitary,
probably both by shared and independent mechanisms. Moreover, we describe how the
evaluation of the AIP-PDE4A5 interaction has proven to be a useful tool for
testing AIP mutations, complementing other in silico, in vitro, and in vivo
analyses. Improved assessment of the pathogenicity of AIP mutations is indeed
paramount to provide adequate guidance for genetic counseling and clinical
screening in AIP mutation carriers, which can lead to prospective diagnosis of
pituitary adenomas.
PMID- 28427100
TI - Dystrophinopathies and Limb-Girdle Muscular Dystrophies.
AB - Muscular dystrophies are a heterogeneous group of inherited diseases. The natural
history of these disorders along with their management have changed mainly due to
a better understanding of their pathophysiology, the evolution of standards of
care, and new treatment options. Dystrophinopathies include both Duchenne's and
Becker's muscular dystrophies, but in reality they are a spectrum of muscle
diseases caused by mutations in the gene that encodes the protein dystrophin.
Duchenne's muscular dystrophy is the most common form of inherited muscle disease
of childhood. The current standards of care considerably prolong independent
ambulation and survival. Several therapeutic options either aiming at
substituting/correcting the primary protein defect or limiting the progression of
the dystrophic process are currently being explored in clinical trials.Limb
girdle muscular dystrophies (LGMDs) are rare and heterogeneous conditions,
characterized by weakness and wasting of the pelvic and shoulder girdle muscles.
Originally classified into dominant and recessive, > 30 genetic forms of LGMDs
are currently recognized. Further understanding of the pathogenic mechanisms of
LGMD will help identifying novel therapeutic approaches that can be tested in
clinical trials.
PMID- 28427101
TI - Tanshinol Alleviates Osteoporosis and Myopathy in Glucocorticoid-Treated Rats.
AB - Tanshinol is a major water-soluble active component of Salvia miltiorrhiza. In
this study, we aimed to investigate whether tanshinol has potential therapeutic
effects against glucocorticoid-induced osteoporosis and glucocorticoid-induced
myopathy. Ninety-six female Sprague-Dawley rats were randomly assigned to five
groups: a control group, a model group, and three model groups treated with 25 or
50 mg/kg of tanshinol, or calcitriol. All model groups received prednisone
acetate for 90 days to induce glucocorticoid-induced osteoporosis. Afterwards,
all animals underwent a surgical procedure to induce bone defects at the right
proximal tibia. Prednisone treatment was stopped after surgery, but tanshinol or
calcitriol treatment was continued to the endpoint. At the experimental endpoint,
compared to the model group, 25 mg/kg tanshinol could significantly reverse
glucocorticoid-induced loss of bone mineral density by 12.5 %, while enhancing
mechanical bone strength, causing a significant 11 % increase in trabecular
number, and reducing trabecular separation by 28 %. In addition, tanshinol
improved the bone microarchitecture and prevented glucocorticoid-induced bone
loss by promoting bone formation and inhibiting bone resorption. Moreover,
results of bone defect repair and muscle weight measurements revealed that
tanshinol accelerated the bone fracture healing process and attenuated muscle
atrophy caused by glucocorticoid. Furthermore, qRT-PCR analysis showed a 1-fold
upregulation in mRNA levels of transforming growth factor beta and roughly 6-fold
increases in vascular endothelial growth factor mRNA expression in calluses from
the tanshinol groups. Tanshinol also preserved muscular ubiquitin mRNA levels
from glucocorticoid-induced elevation. These findings demonstrate the potential
benefits of tanshinol against glucocorticoid-induced osteoporosis and
glucocorticoid-induced myopathy, which warrants further investigation in future
studies.
PMID- 28427102
TI - An Intramolecular CAr-H***O=C Hydrogen Bond and the Configuration of Rotenoids.
AB - Over the past half a century, the structure and configuration of the rotenoids, a
group of natural products showing multiple promising bioactivities, have been
established by interpretation of their NMR and electronic circular dichroism
spectra and confirmed by analysis of single-crystal X-ray diffraction data. The
chemical shift of the H-6' 1H NMR resonance has been found to be an indicator of
either a cis or trans C/D ring system. In the present study, four structures
representing the central rings of a cis-, a trans-, a dehydro-, and an oxadehydro
rotenoid have been plotted using the Mercury program based on X-ray crystal
structures reported previously, with the conformations of the C/D ring system,
the local bond lengths or interatomic distances, hydrogen bond angles, and the H
6' chemical shift of these compounds presented. It is shown for the first time
that a trans-fused C/D ring system of rotenoids is preferred for the formation of
a potential intramolecular C6'-H6'***O=C4 H-bond, and that such H-bonding results
in the 1H NMR resonance for H-6' being shifted downfield.
PMID- 28427103
TI - Saffron Flower Extract Promotes Scratch Wound Closure of Keratinocytes and
Enhances VEGF Production.
AB - During saffron (Crocus sativus) spice production, large amounts of floral
biowaste are generated. It was the aim of this study to develop a value-added
product from saffron floral biowaste to be used as a natural cosmetic ingredient.
HPLC-PDA-MS analysis of saffron flower extracts revealed the presence of
flavonols with the highest amounts in the acetone extract. Kaempferol-3-O
sophoroside was identified as the main flavonoid in the acetone extract (saffron
flower acetone extract). Saffron flower acetone extract and kaempferol-3-O
sophoroside were tested in HaCaT cells for potential effects on cell migration,
proliferation, and for anti-inflammatory properties. Saffron flower acetone
extract concentration dependently (50-200 ug/mL) augmented cell proliferation, as
indicated by an increased BrdU-incorporation, while kaempferol-3-O-sophoroside (1
50 uM) had no effect. Furthermore, treatment of HaCaT cells with saffron flower
acetone extract, but not with kaempferol-3-O-sophoroside, concentration
dependently increased vascular endothelial growth factor secretion (control 49.72
pg/mL vs. saffron flower acetone extract at 200 ug/mL 218.60 pg/mL). Cell
migration was determined using time-lapse microscopy and a modification of the
scratch-wound assay in which saffron flower acetone extract significantly
improved wound closure compared to the untreated control. Overproduction of the
proinflammatory cytokines interleukin-8 and interleukin-6 in HaCaT cells was
induced by TNF-alpha. Kaempferol-3-O-sophoroside (10-50 uM), but not saffron
flower acetone extract, inhibited TNF-alpha-induced IL-8 secretion. The effect
was comparable to 10 uM hydrocortisone (positive control). Interestingly, saffron
flower acetone extract further increased IL-6 levels in TNF-alpha-treated HaCaT
cells in a concentration-dependent manner. In summary, the pronounced wound
healing properties of saffron flower acetone extract present a promising
application for the cosmetic industry.
PMID- 28427104
TI - Pharmacokinetics and Pharmacodynamics of Tofogliflozin (a Selective SGLT2
Inhibitor) in Healthy Male Subjects.
AB - Tofogliflozin is a selective oral inhibitor of sodium-glucose co-transporter 2
for treatment of type 2 diabetes mellitus. The pharmacokinetics,
pharmacodynamics, and safety of tofogliflozin were investigated in healthy male
subjects. Three studies were conducted: single-ascending dose study (10-640 mg)
in 56 Japanese and 24 Caucasian subjects; multiple-ascending dose study (2.5-80
mg once daily for 7 days) in 24 Japanese subjects; and food-effect study (20-40
mg) in 30 Japanese subjects. Tofogliflozin was absorbed rapidly and eliminated
from the systemic circulation with a t1/2 of 5-6 h. Exposure increased dose
proportionally up to 320 mg. Body weight-corrected exposure was similar between
Japanese and Caucasian subjects. Urinary excretion of tofogliflozin ranged from
17.1 to 27.4% of dose. Tofogliflozin did not accumulate with once daily
administration. Food intake decreased Cmax by approximately 30% but did not
change AUC0-inf. Tofogliflozin caused dose-dependent daily urinary glucose
excretion (UGE0-24h), but food intake condition at administration did not affect
it. The exposure-response relationship between plasma average concentration of
tofogliflozin (Cavg) and UGE0-24h fitted Emax model well. There were no serious
adverse events leading to discontinuation or episodes of hypoglycemia. Single and
multiple administration of tofogliflozin were generally well tolerated. Exposure
to tofogliflozin was dose-proportional up to 320 mg and did not accumulate with
multiple once-a-day administration. The model suggests more than 100 ng/mL Cavg
corresponding to the dose of between 20 and 40 mg leads to almost maximum effect
of tofogliflozin.
PMID- 28427105
TI - Optimizing Outcomes in Free Flap Breast Reconstruction in the Community Hospital
Setting: A Stepwise Approach to DIEP/SIEA Flap Procedures with Banking a
Hemiabdominal Flap.
PMID- 28427106
TI - Lateral Ventricle to Sylvian Fissure Shunt for Obstructive Hydrocephalus: First
Report.
AB - Cerebrospinal fluid (CSF) pathway studies have revealed that the CSF secreted
from the choroid plexus of the ventricles after egressing from the fourth
ventricle reaches the basal suprasellar cistern and ultimately the sylvian
cisterns. From the sylvian cistern, the CSF travels over the cerebral convexity
subarachnoid space to reach the superior sagittal sinus and enters the
bloodstream. Diverting CSF from the lateral ventricle with a shunt catheter to
the sylvian cistern can be an option to treat obstructive hydrocephalus. An adult
patient with posttraumatic hydrocephalus with contraindications to
ventriculoperitoneal and ventriculoatrial shunt placement underwent this
procedure of diverting CSF from the lateral ventricle to the sylvian cistern
successfully, and he had immediate relief of symptoms of raised intracranial
pressure. Although preliminary results seem logical and promising, more cases and
longer follow-up is required to consider this shunt operation an option in the
treatment of obstructive hydrocephalus.
PMID- 28427107
TI - ?
PMID- 28427108
TI - An unusual hypoechoic solid mass in the pancreatic head.
AB - Solid pancreatic lesions found on imaging procedures are suspicious for
malignancy and, therefore, demand immediate diagnostic evaluation and therapy. In
the case of indeterminate histology, a primary resection should be considered in
order to preserve the possibility of curative surgery, although rare entities may
be initially disregarded. We present here the case of a 48-year-old female
patient with a hypoechoic lesion of the pancreatic head, which was clearly
delineated from the surrounding pancreatic tissue. The challenging diagnosis of
metastatic leiomyosarcoma could only be established by considering the long-term
clinical history and former histology specimens.
PMID- 28427109
TI - Traveler's Diarrhea, vision abnormalities and unsteady gait in a young woman.
AB - We report on the course of disease in a young woman, originally admitted with
suspected refractory infectious tropical traveler's diarrhea. However, symptoms
did not resolve upon either symptomatic or subsequent antibiotic therapy. When
neurologic deterioration was observed, imaging studies revealed a dramatic series
of thromboembolic events, including intracranial hemorrhage caused by extensive
sinus vein thrombosis as well as thrombi of the right cardiac ventricle. Colonic
mucosal biopsy samples finally led to the histologic diagnosis of ulcerative
colitis. Having excluded thrombophilia or any other disease potentially related
to a prothrombotic state, we interpreted the thromboembolic events as secondary
to the primary manifestation of the underlying inflammatory bowel disease.The
increased risk of thromboembolic complications-especially deep vein thrombosis
and pulmonary embolism-in inflammatory bowel disease is well documented in the
literature. However, sinus vein thrombosis and cardiac thrombi represent a
remarkable dimension of this risk and a rare course of coagulopathy secondary to
an acute flare of ulcerative colitis. Still, there is a lack of awareness of this
risk, resulting in poor implementation of preventive measures modifying risk
factors and allowing for pharmacological prophylaxis. We therefore emphasize that
in line with the 2014 German S3 Guideline-thromboprophylaxis in the setting of an
acute flare of inflammatory bowel disease is mandatory and should not be
restricted because of safety concerns.
PMID- 28427110
TI - ?
PMID- 28427111
TI - [In-vitro activity of mecillinam against urine isolates of Escherichia coli from
outpatient departments in Germany].
AB - National and international guidelines recommend fosfomycin trometamol,
nitrofurantoin, nitroxoline, and pivmecillinam as first-line agents for the
treatment of acute uncomplicated cystitis. Escherichia coli is by far the leading
cause of community-acquired urinary tract infections. Pivmecillinam (X-SYSTO(r))
is an oral prodrug of mecillinam, a penicillin derivative that was reintroduced
to the German market in March 2016. This study aimed to investigate the
proportion of mecillinam-resistant strains among E. coli isolates prior to the
introduction of X-SYSTO(r) in Germany.An in-vitro study was carried out to
determine the minimal inhibitory concentrations (MICs) of mecillinam against 494
urine isolates of E. coli (including multidrug-resistant strains). Isolates were
obtained from outpatients and collected in 25 laboratories between October and
December 2013. MIC breakpoints defined by the European Committee on Antimicrobial
Susceptibility Testing (EUCAST) were applied for classifying the bacterial
isolates as mecillinam-susceptible (MIC <= 8 mg/l) or resistant (MIC > 8
mg/l).The concentrations of mecillinam needed to inhibit 50 % and 90 % of the
test isolates were 1 and 4 mg/l, respectively, for isolates displaying the
extended spectrum beta-lactamase phenotype, and 0.25 and 4 mg/l, respectively,
for the remaining isolates. Overall, 98 % of the isolates were found to be
mecillinam-susceptible (MIC <= 8 mg/l), and 2 % were found to be resistant (MIC >
8 mg/l).These findings support the recommendation to regard pivmecillinam as a
first-line option for the treatment of acute uncomplicated cystitis.
PMID- 28427112
TI - Acute encephalopathy in a 2-year-old pot-bellied pig following accidental
intoxication with clonazepam.
AB - OBJECTIVE: To describe a case of successful management of clonazepam toxicity
causing encephalopathy in a pot-bellied pig. CASE SUMMARY: A 2-year-old female
pot-bellied pig weighing 13.5 kg was presented for evaluation of clinical signs
of acute encephalopathy. Based on the animal's history and clinical signs, a
tentative diagnosis of benzodiazepine (BZP) intoxication was made. The results of
a urinary drug screening test designed to detect illicit substances in human
urine indicated benzodiazepine exposure. Gas chromatography and mass spectrometry
analysis later confirmed clonazepam (urinary concentration 496 ng/mL) as the
intoxicating substance. The pig responded favorably to treatment which included
administration of flumazenil, decontamination with enteral activated charcoal,
and intravenous isotonic crystalloid administration. The pig had a rapid
improvement in mentation 10 minutes following IV flumazenil administration and
was considered mentally appropriate following 24 hours of hospitalization. The
pig was discharged from the hospital after 48 hours of care, and was reported to
be doing well 6 months later. NEW INFORMATION PROVIDED: Intoxication with
prescription benzodiazepines can occur in companion animals and result in
clinical signs of acute encephalopathy. Urinary drug screening tests designed for
human use may provide rapid results to indicate drug intoxication and guide
therapeutic intervention in veterinary species. Administration of flumazenil
resulted in a rapid improvement in mentation following clonazepam intoxication in
a pot-bellied pig.
PMID- 28427113
TI - Simultaneous quantification and semi-quantification of amentoflavone and its
metabolites in human intestinal bacteria by liquid chromatography Orbitrap high
resolution mass spectrometry.
AB - A quick, easy, effective method followed by ultra-high-pressure liquid
chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry
(UHPLC-LTQ-Orbitrap MS) was developed for the simultaneous identification and
quantification of the metabolites produced by amentoflavone (AMF) in human
intestinal bacteria from human feces. The method validated for quantification of
AMF concerning precision, accuracy, recovery, matrix effect, stability and limits
showed acceptable results. Compared with blank human intestinal bacteria
chromatography, three metabolites were identified based on high-accuracy
protonated precursors and multi-stage mass spectrometry (MSn ) using the proposed
strategy. At the same time, a new method was developed for semi-quantification of
three metabolites. We describe the trend over 24 h of concentration-time curves
for AMF and its metabolites. Moreover, the main metabolic pathway of AMF was
clarified in human intestinal bacteria. The method was validated and successfully
applied to the detection and quantification of AMF and its metabolites.
PMID- 28427115
TI - Personality assessment and model comparison with behavioral data: A statistical
framework and empirical demonstration with bonobos (Pan paniscus).
AB - Interest in quantifying consistent among-individual variation in primate
behavior, also known as personality, has grown rapidly in recent decades.
Although behavioral coding is the most frequently utilized method for assessing
primate personality, limitations in current statistical practice prevent
researchers' from utilizing the full potential of their coding datasets. These
limitations include the use of extensive data aggregation, not modeling
biologically relevant sources of individual variance during repeatability
estimation, not partitioning between-individual (co)variance prior to modeling
personality structure, the misuse of principal component analysis, and an over
reliance upon exploratory statistical techniques to compare personality models
across populations, species, and data collection methods. In this paper, we
propose a statistical framework for primate personality research designed to
address these limitations. Our framework synthesizes recently developed mixed
effects modeling approaches for quantifying behavioral variation with an
information-theoretic model selection paradigm for confirmatory personality
research. After detailing a multi-step analytic procedure for personality
assessment and model comparison, we employ this framework to evaluate seven
models of personality structure in zoo-housed bonobos (Pan paniscus). We find
that differences between sexes, ages, zoos, time of observation, and social group
composition contributed to significant behavioral variance. Independently of
these factors, however, personality nonetheless accounted for a moderate to high
proportion of variance in average behavior across observational periods. A
personality structure derived from past rating research receives the strongest
support relative to our model set. This model suggests that personality variation
across the measured behavioral traits is best described by two correlated but
distinct dimensions reflecting individual differences in affiliation and
sociability (Agreeableness) as well as activity level, social play, and neophilia
toward non-threatening stimuli (Openness). These results underscore the utility
of our framework for quantifying personality in primates and facilitating greater
integration between the behavioral ecological and comparative psychological
approaches to personality research.
PMID- 28427114
TI - Lifestyle use of drugs by healthy people for enhancing cognition, creativity,
motivation and pleasure.
AB - Today, there is continued, and in some cases growing, availability of not only
psychoactive substances, including treatments for mental health disorders such as
cognitive enhancers, which can enhance or restore brain function, but also
'recreational' drugs such as novel psychoactive substances (NPS). The use of
psychoactive drugs has both benefits and risks: whilst new drugs to treat
cognitive symptoms in neuropsychiatric or neurodegenerative disorders could have
great benefits for many patient groups, the increasing ease of accessibility to
recreational NPS and the increasing lifestyle use of cognitive enhancers by
healthy people means that the effective management of psychoactive substances
will be an issue of increasing importance. Clearly, the potential benefits of
cognitive enhancers are large and increasingly relevant, particularly as the
population ages, and for this reason, we should continue to devote resources to
the development of cognitive enhancers as treatments for neurodegenerative
diseases and psychiatric disorders, including Alzheimer's disease, attention
deficit hyperactivity disorder and schizophrenia. However, the increasing use of
cognitive enhancers by healthy individuals raises safety, ethical and regulatory
concerns, which should not be ignored. Similarly, understanding the short- and
long-term consequences of the use of NPS, as well as better understanding the
motivations and profiles of users could promote more effective prevention and
harm reduction measures. Linked Articles This article is part of a themed section
on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the
other articles in this section visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.
PMID- 28427117
TI - [Standardize the diagnosis and treatment of thyrotropin-secreting pituitary
tumors].
PMID- 28427116
TI - Current Trends in the Management of Gastroesophageal Reflux Disease.
AB - Gastroesophageal reflux disease (GERD) characterized by heartburn and/or
regurgitation symptoms is one of the most common gastrointestinal disorders
managed by gastroenterologists and primary care physicians. There has been an
increase in GERD prevalence, particularly in North America and East Asia. Over
the past three decades proton pump inhibitors (PPIs) have been the mainstay of
medical therapy for GERD. However, recently there has been an increasing
awareness amongst physicians and patients regarding the side effects of the PPI
class of drugs. In addition, there has been a marked decline in the utilization
of surgical fundoplication as well as a rise in the development of nonmedical
therapeutic modalities for GERD. This review focuses on different management
strategies for GERD, optimal management of refractory GERD with special focus on
available endoluminal therapies and the future directions.
PMID- 28427118
TI - [Strengthen multidisciplinary collaboration to enhance the level of diagnosis and
treatment of thyrotropin secreting adenoma].
PMID- 28427119
TI - [Genetic analysis of posterior cranial fossa morphology in families of Chiari
malformation type I].
AB - Objective: To explore genetic characteristic of posterior cranial fossa
morphology in families of Chiari malformation type I (CMI). Methods: From April
2010 to May 2016, a total of 47 cases of CMI families (CMI group) and their 94
parents (CMI-P group)collected were retrospectively reviewed in Department of
Spinal Surgery, Drum Tower Hospital, School of Medicine, Nanjing
University.Another cohort of 50 asymptomatic adults was enrolled to serve as the
control group.Patients with skull fracture or other diseases which can lead to
secondary CMI were excluded.On mid-sagittal T2-weighted magnetic resonance (MR)
imaging, four measurements were evaluated and compared between these three
groups, including the length of cerebellar tonsillar descent, the area of
posterior cranial fossa(PCF area), the area of the brain tissue in posterior
cranial fossa (PCF tissue area), and the PCF crowdedness indexes (PCF tissue
area/ PCF area*100%). Results: Totally 47 CMI patients (21 males and 26 females;
mean age, 16.4 years), 94 parents (47 males and 47 females; mean age, 39.2 years)
and 50 controls (23 males and 27 females; mean age, 22.3 years) were recruited in
this study.Significant differences in all four indexes were found between CMI
group and the control group.The length of cerebellar tonsillar descent were much
bigger in CMI-P group than in the control group (1.5+/-2.2 mm vs -0.9+/-1.1 mm),
with 7 cases reach the diagnostic criteria of Chiari malformation(>=5 mm) and one
with syingomyelia.Compared to the control group, CMI-P group had smaller PCF
area, and its PCF crowdedness indexes averaged 90.0% as between the control group
(85.3%) and the CMI group (93.6%). Conclusions: In CMI families, parents have
similar posterior cranial fossa abnormalities with their CMI children, presenting
obviously narrow and crowded.Their PCF crowdedness indexes are between normal
subjects and CMI patients, and their cerebellar tonsils are lower, even some
parents are also CMI patients, suggesting genetic mechanisms involved in the
development of CMI.
PMID- 28427120
TI - [Arthroscopic treatment of eldly with massive rotator cuff tear].
AB - Objective: To investigate the surgical technique and clinical efficacy of
arthroscopic treatment of the elderly patients with massive rotator cuff tear.
Methods: From June 2012 to June 2015, thirty-six patients with massive rotator
cuff tear were treated with arthroscopic and followed up. The visual analog
scale(VAS)pain score, University of California Los Angeles (UCLA) scores,
Constant scores and American Shoulder and Elbow Surgeons scale(ASES)were used
before and after the arthroscopic surgery. Results: All the patients were
followed up for average of 18.5 (12 to 30) months.Before arthroscopic surgery,
the VAS, UCLA, Constant, ASES were (6.1+/-2.2), (10.6+/-4.3), (40.3+/-10.5) and
(28.8+/-18.5) points; the average flexion of the shoulder was (76.5+/-42.6)
degrees , the average abduction of the shoulder was (72.4+/-35.2) degrees , the
average external rotation of the shoulder was(26.6+/-22.2) degrees and the
average internal rotation of the shoulder was (20.2+/-6.2) degrees
respectively.These scores were improved to (1.4+/-1.2), (30.4+/-5.2), (82.6+/
12.6), and (78.8+/-22.6) points, the average flexion of the shoulder was improved
to (152.8+/-25.6) degrees , the average abduction of the shoulder was improved to
(120.6+/-32.8) degrees , the average external rotation of the shoulder was
improved to (42.6+/-16.2) degrees and the average internal rotation of the
shoulder was improved to (38.4+/-5.6) degrees after one-year follow-up
period.Improvement in these scores and range of motion(ROM) were significant
difference(P<0.05). Conclusion: Arthroscopic repair can effectively treat the
eldly patient with massive rotator cuff tear and obviously improve the function
of shoulder joint. The surgery has a clinical application value.
PMID- 28427121
TI - [Efficacy and safety of vertebrae pedicle subtraction osteotomy by posterior
trans apical for correction of severe and rigid idiopathic scoIiosis].
AB - Objective: To evaluate the efficacy and safety of pedicle subtraction osteotomy
for correction of severe rigid idiopathic scoliosis. Methods: From January 2003
to December 2014, eighteen patients with severe rigid idiopathic scoliosis were
treated by posterior wedge osteotomy in department of spinal surgery, the First
Affiliated Hospital of Xinjiang Medical University. There were 5 males and 13
females, and the average age at was (16.9+/-9.1)years, and the average follow-up
was 47.6 months. The coronal and sagittal Cobb's angles, sagittal trunk shifts,
apical vertebral translation, height change and fusion segments were measured on
standing AP and lateral radiographs before, after surgery and the final follow
up. Results: The Cobb's angle in the coronal plane was corrected from (94.3+/
13.3) degrees to (31.6+/-14.8) degrees , representing 64.8% correction rate. The
Cobb's angle in the sagittal plane was corrected from (62.5+/-17.8) degrees to
(27.1+/-11.7) degrees , representing 82.6% correction rate. Coronal trunk shift
was obviously improved from -29.8 mm to -3.5 mm. the average fusion segments was
13.7+/-1.8 ranging from 11 to 17 segments. Perioperative complications consisted
of pleura injury in 4 cases, cerebrospinal fluid leakage in 2 cases transient
neurological damage in 2 cases and delayed infection in 1 case. Conclusion:
Pedicle Subtraction Osteotomy correction by the single posterior approach is a
reliable and safe surgical technique for correction of severe rigid idiopathic
scoliosis.
PMID- 28427122
TI - [Application on the quantitative perfusion parameters of dynamic contrast
enhanced MRI in the pathological subtype of uterine leiomyoma].
AB - Objective: To analyze the value of the quantitative perfusion parameters of
dynamic contrast-enhanced MRI(DCE-MRI) in the pathological subtype of uterine
leiomyoma. Methods: A total of 35 cases of uterine leiomyoma confirmed by surgery
and pathology were retrospectively analyzed in Shaoxing People's Hospital from
October 2015 to May 2016.All cases underwent DCE-MRI. Quantitative perfusion
parameters were prospectively measured and analyzed, including transfer constant
(K(trans)) , efflux rate constant (K(ep)), extravascular extracellular space
volume ratio (V(e)), blood plasma volume ratio (V(p)), permeability surface area
product (PS) and plasma flow (F(p)) , using signal-input two-compartment tracer
kinetic models (Extended Tofts model and Exchange model) in 35 leiomyoma
cases.After the operation, the 35 cases were divided into three groups according
to the pathological classfication , the ordinary, the cellular and the
degeneration type.To analyze the differences among the three groups about the
quantitative perfusion parameters of uterine leiomyoma. Compared with the gold
standard of pathological findings, the ROC curves were drawn to evaluate the
diagnostic efficacy of different quantitative perfusion parameters. Results: In
the ordinary, cellular and degeneration type of uterine leiomyoma, K(trans) value
were respectively(0.684+/-0.341), (1.897+/-0.458), (0.554+/-0.514)/min; K(ep)
were respectively(1.004+/-0.685), (2.362+/-1.001), (1.274+/-1.093)/min; V(e) were
respectively 0.789%+/-0.186%, 0.806%+/-0.203%, 0.537%+/-0.314%; V(p) were
respectively 0.145%+/-0.196%, 0.502%+/-0.338%, 0.062%+/-0.106% and F(p) were
respectively(0.792+/-0.461), (2.426+/-0.509), (0.628+/-0.551)ml/min.Among three
groups, the value of K(trans), K(ep), V(e), V(p) and F(p) had statistical
difference(all P<0.05), the value of PS didn't have statistical difference. The
value of K(trans), K(ep), V(p) and F(p) in cellular type were higher than the
ordinary type(all P<0.01); the value of K(trans), V(p) and F(p) in cellular type
were higher than the degeneration type(all P<0.01); the value of V(e) in ordinary
type was higher than the degeneration type(P<0.05). The area under ROC curve was
0.981 for K(trans), 0.904 for K(ep), 0.622 for V(e), 0.840 for V(p) and 0.994 for
F(p). Conclusion: The quantitative perfusion parameters of DCE-MRI , especially
the value of K(trans), K(ep), V(p) and F(p) have a great diagnostic efficacy in
the pathological classfication of uterine leiomyoma which will become a
predictive factor of pathological classfication in uterine leiomyoma.
PMID- 28427123
TI - [Predictive value of liver pathologic changes in determining the effectiveness of
entecavir treatment for chronic hepatitis B-An analysis of 1 366 cases].
AB - Objective: To analyze the relationship between baseline liver pathologic changes
and the effectiveness of entecavir(ETV) and investigate the predictive value of
baseline liver pathologic changes in determining the effectiveness of ETV, to
provide reliable basis for precision medicine in patients with chronic hepatitis
B(CHB). Methods: A total of 1 366 cases with CHB were retrospectively recruited
who underwent liver biopsy between January 2006 to June 2016 and were treated
with ETV over 96 weeks.The relationship between baseline liver pathologic changes
and the antiviral responses to ETV at 48, 96 weeks were compared. Results: Liver
pathology was employed to make the definite inflammation grade and the fibrosis
stage.According to the liver inflammation and fibrosis, patients were divided
into 4 groups(G1, G2, G3, G4 and S1, S2, S3, S4 respectively). The complete
response rate of G1, G2, G3 and G4 after 48 weeks ETV treatment was 26.3%(10/38),
30.9%(121/391), 35.3%(101/286), 44.4%(52/117) respectively in HBeAg positive
patients and was 61.5%(24/39), 80.4%(148/184), 82.4%(201/244), 88.1%(59/67)
respectively in HBeAg negative patients.There was statistical difference in the
complete response rates among liver inflammation grades both in HBeAg positive
patients(chi(2)=8.510, P<0.05) and in HBeAg negative patients(chi(2)=12.054,
P<0.05)respectively.The differences were still statistical significant after 96
weeks ETV treatment (P<0.05). The complete response rates of S1, S2, S3 and S4
after 48 weeks ETV treatment were 39.0%(41/105), 37.8%(127/336), 30.9%(97/314),
24.7%(19/77), respectively in HBeAg positive patients and was 85.7%(30/35),
84.4%(92/109), 83.9%(162/193), 75.1%(148/197) respectively in HBeAg negative
patients. Whether HBeAg was positive or not, the rates were in decline but there
was no statistical difference in the complete response rates among liver fibrosis
stages(chi(2)=7.765, P>0.05; chi(2)=6.729, P>0.05). The differences were still
not statistical significant after 96 weeks ETV treatment (P>0.05). But after
further grouping, whether HBeAg was positive or not, as the degree of fibrosis
stage was aggravating, the complete response rate of G2, G3 and G4 after 48 weeks
ETV treatment decreased at the same degree of inflammation grade and the
differences were statistically significant (P<0.05). The differences were still
statistical significant after 96 weeks ETV treatment (P<0.05). Conclusions: The
responses to ETV treatment are closely related with baseline liver pathology.The
CHB patients with higher score of inflammation and lower score of fibrosis will
have a good response to ETV treatment.The degree of inflammation grades and
fibrosis stages can be used as early predictors of ETV treatment for CHB.
PMID- 28427124
TI - [Contemporary use of ticagrelor in patients with acute coronary syndrome after
discharge].
AB - Objective: To investigate the degree and determinants of using ticagrelor among
discharged patients with acute coronary syndrome (ACS). Methods: Patients with
ACS in Fuwai hospital who were given ticagrelor after discharge between Jan. 2015
to Jun. 2015 were analyzed.The clinical characteristics and adherence to
ticagrelor of these patients were collected by reviewing the electronic medical
records and telephone interview.Date were statistically-analyzed. Results: Among
all screened 404 patients, 158 (39.1%) patients prematurely stopped ticagrelor
within 12 months, while 119(29.5%) patients switched from ticagrelor to
clopidogrel.Unavailable locally (34.8%), economic reasons (17.7%) and hemorrhagic
events (18.4%) were the main causes of the premature discontinuation of
ticagrelor.Univariate analysis showed left main disease (P=0.04) and the
frequency of outpatient follow-up (P<0.01) as relative factors for prematurely
stopping ticagrelor outside hospital after discharge.Multivariate analysis
revealed medical insurance payment (OR 1.79, 95%CI 1.03-3.11) and the frequency
of outpatient follow-up (OR 0.61, 95%CI 0.43-0.86) as independent predictors of
prematurely stopping ticagrelor outside hospital.Prematurely stopping ticagrelor
has no significant effect on the ischemic events (myocardial infaction or stroke)
(P=0.76). Conclusion: Social cinditions is the main factor for the persistence to
ticagrelor among ACS patients after dischcrge.Medical insurance payment and low
frequency of outpatient follow-up were independent predictors of prematurely
stopping ticagrelor and it may not have impact on ischemic events.
PMID- 28427126
TI - [Patency rate of autogenous arteriovenous fistula after repairment in the
patients with late fistula dysfunction/faliure].
AB - Objective: To invesitigate 3-year patency rate of autogenous arteriovenous
fistula(AVF)in the patients with late fistula dysfunction/failure. Methods: The
prospective study was carried out in the First Hospital of Tsinghua University
from March 2012 to March 2013. A total of 136 maintenance hemodialysis patients
with late AVF dysfunction/faliure who received AVF repairment were enrolled in
the study. All the patients were divided into three groups according to surgical
procedures: venous neointimal hyperplasia (VNH) stripping group (group A), non
VNH stripping group (group B) and creation of a new AVF group (group C). Patency
rate was calculated by survival analysis method, and survival curve of fistula
was drawn as well. Results: During 12-36 months follow-up, there were 46 patients
with late AVF dysfunction/faliure in group A, 38 patients in group B, and 52
pateints in group C. The AVF patency rate was 88.6% at 12th month, 77.6% at 24th
month, and 57.2% at 36th month in group A; 89.3% at 12th month, 74.5% at 24th
month, and 55.1% at 36th month in group B; 88.1% at 12th month, 76.8% at 24th
month, and 59.0% at 36th month in group C. The AVF patency rates had no
statistical difference among three groups at three time points (12th, 24th and
36th month) (P>0.05). Conclusion: The patency rate was high in the patients who
recieved AVF repairment. There was no significant difference in the patency rate
among three different surgical treatments.
PMID- 28427125
TI - [The clinical value of SUDOSCAN in diagnosis of diabetic distal symmetrical
peripheral neuropathy].
AB - Objective: To evaluate the clinical value of SUDOSCAN in diagnosis of diabetic
distal symmetrical peripheral neuropathy. Methods: According to the diagnostic
criteria for multiple diabetic distal symmetrical peripheral neuropathy, a total
of 130 patients with type 2 diabetes mellitus (T2DM) in Department of
Endocrinology, the Affiliated Hospital of Qingdao University between August 2015
and July 2016 were divided into two groups, diabetic peripheral neuropathy group
(DPN group, 50 cases) and non-diabetic peripheral neuropathy group (NDPN group,
80 cases). Additional 80 healthy volunteers were selected as healthy control
group (NC group). SUDOSCAN was employed to detect electrochemical skin
conductance (ESC, the unit was MUS) of subjects' hands and feet, and the
correlation between sensory nerve conduction velocity (SCV) and ESC was analyzed
as well. Results: The average hands ESC in NC and T2DM group were (79.1+/-10.4)
MUS and (59.7+/-18.1) MUS, respectively; the average feet ESC were (82.0+/-8.2)
MUS and (62.1+/-21.8) MUS, respectively (both P<0.01). The average hands ESC in
DPN and NDPN group were (53.2+/-18.9) MUS and (63.7+/-16.5) MUS; the average feet
ESC were (53.5+/-24.4) MUS and (67.4+/-18.2) MUS, respectively (both P<0.05). The
hands and feet ESC were positively correlated with SCV, and the correlation
coefficient were 0.425 and 0.445, respectively (both P<0.01). The area under the
receiver operating characteristic curve (ROC) of hands and feet ESC to evaluate
diabetic symmetrical peripheral polyneuropathy were 0.785 and 0.768 (both
P<0.01). Conclusion: SUDOSCAN is a promising tool for the diagnosis of diabetic
symmetrical peripheral polyneuropathy.
PMID- 28427127
TI - [Surgical management of ophthalmic artery aneurysms via minimally invasive
frontolateral approach].
AB - Objective: To explore the minimally invasive techniques and outcome of carotid
ophthalmic artery aneurysms clipping via a frontolateral approach. Methods: The
clinical data of 95 patients with carotid ophthalmic artery aneurysms treated via
frontolateral approach in the last 1.5 years in Beijing Tiantan Hospital and
Beijing Anzhen Hospital were analyzed retrospectively.Before the operation,
digital subtraction angiogram (DSA) was performed among all patients.The patients
were divided into two groups by the lateral approach.According to preoperative
classification, surgical characteristics and prognosis were summarized. Results:
Ninety-five cases of ophthalmic aneurysms were divided into type I of 44 cases
(46.3%), type II of 34 cases (35.7%) and type III of 17cases (17.9%), according
to the results of DSA.The diameter of aneurysm was <10 mm (35 cases), 10-25 mm
(34 cases), and >25 mm (26 cases). In the 17 cases of subarachnoid hemorrhage
(SAH), 8 cases were ruptured carotid-ophthalmic artery aneurysms.Among those 95
patients, 93 were clipped successfully, 2 was trapped.Multiple aneurysms in 5
cases were treated in one surgical session through the same approach.No aneurysm
residual was found after postoperative CTA review.Ipsilateral vision of 3 cases
were decline.Cerebral infarction was appeared in 9 cases.All the others had a
good recovery. Conclusions: The carotid-ophthalmic artery aneurysms could be well
exposed. Microsurgery through frontolateral approach has the advantages such as
minimal invasion, less effect on the patients' look and simple procedure.The
frontolateral approach is safe and effective in surgery for ophthalmic segment of
the internal carotid artery aneurysms.
PMID- 28427128
TI - [The application value of contrast-enhanced ultrasound in the surgery of renal
masses].
AB - Objective: To investigate the clinical value of contrast-enhanced ultrasound in
the diagnosis of renal masses. Methods: A total of 50 patients with renal masses
who underwent partial nephrectomy were analyzed from January 2014 to October 2016
in the Department of Urology of China-Japan Union Hospital of Jilin University.In
the intraoperative contrast-enhanced ultrasound, the characteristics of
ultrasound imaging were recorded including location, size, boundary, echo, real
time internal and peripheral blood and renal pelvis distance, artery, guidance on
the selection of surgical methods, intraoperative real-time estimation of the
extent of tumor resection. Results: In the 50 patients, there were 49 cases
enhancement in the imaging of the cystic masses, 1 case had no
enhancement.Contrast-enhanced ultrasound assisted clinical accurate positioning
34 masses which were in the renal contour and not convex.And 15 patients were
found main arteries of renal occupied lesions.There were 38 cases whose distance
from occupying to pelvis was more than 0.5 cm, and maintained the original
operation scheme for partial nephrectomy.There were 12 cases whose distance from
occupying to pelvis was less than 0.5 cm, and proceeded radical resection.
Conclusions: Intraoperative contrast-enhanced ultrasound can provide a more
accurate imaging basis for the surgeon in partial nephrectomy.It's of great
significance for the correct choice of surgical procedures, and can reduce or
avoid the occurrence of postoperative complications.
PMID- 28427129
TI - [The role of FOXO3a-Bim signaling in triptolide induced bladder cancer T24 cells
apoptosis].
AB - Objective: To investigate the role of FOXO3a-Bim signaling in triptolide induced
bladder cancer T24 cells apoptosis. Methods: T24 cells were used and divided into
control group, triptolide group(50 nmol/L), MK2206 group(50 nmol/L triptolide+ 5
MUmol/L MK2206), FOXO3a-siRNA group(50 nmol/L triptolide+ 100 nmol/L FOXO3a
siRNA), Bim-siRNA group (50 nmol/L triptolide+ 100 nmol/L Bim-siRNA). MTT assay
was used to analyze the cells growth inhibition.Annexin V/PI staining was
implemented to detect cell apoptosis rate, the expression of p-Akt, Akt, p
FOXO3a, FOXO3a, Bim, Bax.Cleaved-caspase 3 was analyzed by Western blot. Results:
After treatment with triptolide 25, 50, 100, 250 nmol/L, the cell growth
inhibition rates at 24 hours(17%+/-9%, 24%+/-5%, 43%+/-8%, 61%+/-8%), 48 hours
(20%+/-7%, 34%+/-6%, 56%+/-7%, 74%+/-5%) and 72 hours(32%+/-8%, 41%+/-7%, 69%+/
7%, 84%+/-3%) were significantly higher than control group respectively.The
IC(50) at 24, 48, 72 hours were (113+/-10), (91+/-8), (68+/-5) nmol/L; the cell
apoptosis rates at 24 hours (10%+/-4%, 15%+/-5%, 29%+/-8%, 46%+/-8%), 48 hours
(16%+/-5%, 24%+/-6%, 40%+/-7%, 55%+/-9%) and 72 hours (27%+/-4%, 38%+/-5%, 50%+/
9%, 65%+/-8%) were significantly increased (P<0.05). Western blot showed that
triptolide reduced the expression of p-Akt, p-FOXO3a and increased the expression
of Bim, Bax, cleaved-caspase 3.The cell inhibition rate in Triptolide group
(30%+/-8%) was significantly higher than that in the control group (P<0.05) and
the rates in MK2206 group (54% +/-6%), FOXO3a-siRNA group (18%+/-7%) and Bim
siRNA group (11%+/-6%) were also higher than the control group.Compared with the
triptolide group, the inhibition rate in MK2206 group was significantly
increased, but decreased in FOXO3a-siRNA group and Bim-siRNA group(P<0.05).
Conclusion: Triptolide induces T24 cells apoptosis through FOXO3a-Bim signaling
pathway.
PMID- 28427130
TI - [To see the future development of burn medicine from the view of holistic
integrative medicine].
AB - The therapeutic methods and effects have been improved greatly in the past few
decades for burn care and management with several important advancements which
have resulted in more effective patient stabilization and significantly decreased
mortality in China. However, the challenges still exist, such as how to further
improve the recovery of the patients' appearance and function, and how to advance
the treatment of severe deep extensive burn injury, etc. The theory of holistic
integrative medicine (HIM) provides a new opportunity for the development of
clinical medicine. This article emphasizes the important roles of HIM in
exploration of burn medicine, considering the advanced development of modern life
sciences and relevant techniques.
PMID- 28427131
TI - [Recognizing prevention and treatment of burn sepsis with the concept of holistic
integrative medicine].
AB - Sepsis remains a major cause of death in severe burns. The effect of sepsis
management is influenced by its complicated pathophysiologic changes. In order to
improve the outcome of burn sepsis, the predisposing factor of sepsis after burn
analyzed by advanced technology, the early prevention, antibiotics therapy, and
combined treatment in severe burns with sepsis are discussed using the concept of
holistic integrative medicine.
PMID- 28427132
TI - [Influences of abaR gene on biofilm formation of Acinetobacter baumannii].
AB - Objective: To detect drug-resistant phenotype and abaR gene of Acinetobacter
baumannii (AB) and investigate influences of abaR gene on biofilm formation of
AB. Methods: From February to July 2014, 159 strains AB were collected from
Department of Clinical Microbiology of Ruijin Hospital of School of Medicine of
Shanghai JiaoTong University and numbered starting from 1 according time when
they were collected. (1) The above-mentioned 159 strains of AB were identified by
detecting gene sequence of 16S ribosomal DNA. According to results of drug
sensitivity test, extensively drug-resistant strains and sensitive strains of AB
were selected and counted, and their sources were recorded. (2) Extensively drug
resistant strains and sensitive strains of AB were collected to measure biofilm
formation (denoted as absorbance value) by methyl thiazolyl tetrazolium method
when strains at culture hour 12, 24, 48 and 72. (3) The abaR gene sequence of
ATCC 17978 of AB was analyzed through Gene banks of National Center for
Biotechnology Information and compared with AqsR gene sequence of LuxR type
receptor of Acinetobacter oleivorans DR1. No. 87 and No. 96 AB strains were
amplified and sequenced by polymerase chain reaction according to target gene
sequence of abaR of ATCC 17978 of AB. The sequencing result was compared with
abaR gene sequence of ATCC 17978. (4) No. 87 and No. 96 AB strains were collected
and divided into 0.1% dimethyl sulfoxide (DMSO) group, 10 MUmol/L N-heptanoyl-L
Homoserine lactone (C7-HSL) group, 10 MUmol/L N-(3-Hydroxydodecanoyl)-DL
homoserine lactone (OH-dDHL) group, 1% DMSO group, 100 MUmol/L C7-HSL group, and
100 MUmol/L OH-dDHL, with 3 wells of each group. AB strains in the above groups
were respectively dealt with DMSO of corresponding final volume fraction, C7-HSL
and OH-dDHL of corresponding final amount-of-substance concentration. Biofilm
formation (denoted as absorbance value) of AB was measured by methyl thiazolyl
tetrazolium method at culture hour 12, 24, 48 and 72. Data were processed with
analysis of variance of factorial design, one-way analysis of variance, LSD test
and Bonferroni correction. Results: (1) There were 18 extensively drug-resistant
strains and 5 sensitive strains of AB. Samples of extensively drug-resistant
strains were mainly collected from Emergency ICU and Department of Burns and
Plastic Surgery of our hospital and were mainly from sputum, blood, and wound
exudate. Samples of sensitive strains were collected dispersedly and were mainly
from sputum. (2) Absorbance values of extensively drug-resistant strains and
sensitive strains of AB at all culture time points were similar (with P values
above 0.05). Absorbance value of extensively drug-resistant strains of AB at
culture hour 24 was obviously higher than that of these strains at culture hour
12, 48, or 72 (with P values below 0.01). Absorbance value of sensitive strains
of AB at culture hour 24 was obviously higher than that of these strains at
culture hour 12 (P<0.01). (3) AbaR gene sequence of LuxR type receptor existed in
AB. Similarity ratio between abaR gene sequence and LuxR type receptor AqsR gene
sequence in Acinetobacter oleivorans DR1 was 87%. Similarity ratios between abaR
gene sequence of No. 87 and No. 96 strains and ATCC 17978 of AB were 98% and 99%,
respectively. (4) Absorbance values of 0.1% DMSO group of No. 87 strain at all
culture time points were similar to those of 1% DMSO group (with P values above
0.05). Absorbance value of 0.1% DMSO group of No. 96 strain at culture hour 12
was obviously lower than that of 1% DMSO group (P<0.01), while that at culture
hour 24 was obviously lower than that of 1% DMSO group (P<0.01). Absorbance
values of 10 MUmol/L C7-HSL group of No. 87 and No. 96 strains at culture hour 24
were obviously lower than those of 0.1% DMSO group (with P values below 0.01).
Absorbance values of 100 MUmol/L C7-HSL group of No. 87 strain at all culture
time points were similar to those of 1% DMSO group, respectively (with P values
above 0.05). Absorbance value of 100 MUmol/L C7-HSL group of No. 96 strain at
culture hour 12 was lower than that of 1% DMSO group (P<0.01). Absorbance values
of 10 MUmol/L OH-dDHL group of No. 87 and No. 96 strains were similar to those of
0.1% DMSO group (with P values above 0.05). Absorbance values of 100 MUmol/L OH
dDHL group of No. 87 strain at all culture time points were similar to those of
1% DMSO group (with P values above 0.05). Absorbance value of 100 MUmol/L OH-dDHL
group of No. 96 strain at culture hour 12 was obviously higher than that of 1%
DMSO group (P<0.01). Absorbance values of 0.1% DMSO group and 1% DMSO group of
No. 87 and No. 96 strains at culture hour 24 were obviously higher than those at
culture hour 12 and 48 (with P values below 0.01). Conclusions: Extensively drug
resistant strains of AB exist commonly. AbaR gene exists in AB has relation with
biofilm formation of AB.
PMID- 28427133
TI - [Effects of application of vancomycin in the early stage of patients with
extremely severe burn].
AB - Objective: To evaluate the effects of application of vancomycin in the early
stage of patients with extremely severe burn, in order to provide reference to
drug for anti-infection treatment in the early stage of patients with extremely
severe burn. Methods: Data of 15 patients of Kunshan explosion on August 2nd,
2014, admitted to the Department of Intensive Care in our hospital were
retrospectively analyzed. The clinical efficacy of continuously intravenous
dripping of vancomycin (combined with imipenem) in the early stage of burns
(before and on post burn day 14) was analyzed. (1) The steady state plasma
concentration of vancomycin was monitored respectively 30 min before the third,
sixth, and tenth medication with direct chemiluminescent imaging method. (2) The
distribution of Gram-positive bacteria of patients during hospitalization and
their drug resistance to 14 antibiotics commonly used in clinic were analyzed.
(3) Serum level of procalcitonin (PCT), white blood cell count, percentage of
neutrophils before and after treatment, and efficacy grade of anti-infection
treatment in the early stage of burns were analyzed. (4) Serum levels of
aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine before
and after treatment, and the adverse effects during medication were analyzed. The
WHONET 5.5 statistical software was used to analyze the distribution of Gram
positive bacteria in all the pathogens, and the status of drug resistance of Gram
positive bacteria to 14 antibiotics. Data were processed with Wilcoxon rank sum
test. Results: (1) Twenty-nine times of steady state plasma concentration
monitoring were performed in the patients in total, with the steady state plasma
concentration of vancomycin from 4.3 to 42.1 MUg/mL. In the monitoring before
third, sixth, and tenth medication, the percentages of result reaching the
standard were respectively 1, 3/14, and 2/7. (2) A total of 79 Gram-positive
bacteria were isolated, including 49 (62.03%) strains of Staphylococcus aureus, 9
(11.39%) strains of Staphylococcus haemolyticus, 7 (8.86%) strains of
Staphylococcus epidermidis, 12 (15.19%) strains of Enterococcus faecium, and 2
(2.53%) strains of Enterococcus faecalis. The above-mentioned Staphylococcus
strains were with high drug resistance to antibiotics including penicillins,
erythromycin, ciprofloxacin, and low drug resistance to linezolid, teicoplanin,
and nitrofurantoin. The above-mentioned Enterococcus strains were with high drug
resistance to antibiotics including erythromycin, ciprofloxacin, gentamicin, and
low drug resistance to linezolid and teicoplanin. The above-mentioned
Staphylococcus strains were all sensitive to vancomycin. Two strains of
vancomycin-resistant Enterococcus were detected in the above-mentioned
Enterococcus strains. (3) Serum level of PCT, white blood cell count, percentage
of neutrophils of patients were (8.1+/-7.5) ng/mL, (24+/-10)*10(9)/L, and 0.898+/
0.029 before treatment, which were significantly higher than (3.0+/-2.8) ng/mL,
(12+/-5)*10(9)/L, and 0.867+/-0.016 after treatment (with Z values respectively
2.103, -3.237, and -3.068, P<0.05 or P<0.01). After the early treatment,
excellence, progess, and invalid results were achieved in 7, 5, and 3 patients,
with the effective percentage of 4/5 in clinic. (4) There were no statistically
significant differences in serum levels of AST, ALT, and creatinine of patients
between before and after treatment (with Z values respectively-0.057, -1.508, and
-1.363, P values above 0.05). Only one patient had liver and renal dysfunction
during treatment. Conclusions: The positive and reasonable use of vancomycin can
remove most of the Gram-positive bacteria, and control the development of sepsis
combined with imipenem in the early stage of patients with extremely severe burn.
However, the dose of vancomycin should be individualized and the steady state
plasma concentration should be monitored to maintain the blood concentration
within the safe and effective range, so as to improve the rational use of
vancomycin.
PMID- 28427134
TI - [Role of bone marrow tyrosine kinase on chromosome X in the production of pro
inflammatory cytokines from mouse mononuclear-macrophages RAW264.7 induced by
endotoxin/lipopolysaccharide and its mechanism].
AB - Objective: To investigate the role of bone marrow tyrosine kinase on chromosome X
(BMX) in the production of tumor necrosis factor alpha (TNF-alpha) and
interleukin-1beta (IL-1beta) from mouse mononuclear-macrophages induced by
endotoxin/lipopolysaccharide (LPS) and its related mechanism. Methods: Mouse
mononuclear-macrophages RAW264.7 were inoculated in 6-well plates and routinely
cultured for the following experiments. (1) Cells were collected and divided into
blank control group, LPS control group, and 75, 750, 7 500, 75 000 nmol/L BMX-IN
1 pretreatment groups according to the random number table, with 8 wells in each
group. Cells in blank control group were routinely cultured for 25 h. Cells in
LPS control group were routinely cultured for 24 h and stimulated by LPS in the
final mass concentration (the same below) of 0.1 MUg/mL for 1 h. Cells in the
latter 4 groups were pretreated with BMX-IN-1 in the final molarity (the same
below) of 75, 750, 7 500, 75 000 nmol/L for 24 h and stimulated by 0.1 MUg/mL LPS
for 1 h. The mRNA expression of TNF-alpha of cells in each group was determined
by real-time fluorescent quantitative reverse transcription polymerase chain
reaction (RT-PCR) to screen the optimum concentration of BMX-IN-1. (2) Cells were
collected and divided into LPS control group and 2, 4, 8, 12, 18 h BMX-IN-1
pretreatment groups according to the random number table, with 8 wells in each
group. Cells in LPS control group were stimulated by 0.1 MUg/mL LPS for 1 h.
Cells in the latter 5 groups were pretreated with optimum concentration of BMX-IN
1 for 2, 4, 8, 12, 18 h respectively and stimulated by 0.1 MUg/mL LPS for 1 h.
The mRNA expression of TNF-alpha of cells in each group was determined by real
time fluorescent quantitative RT-PCR to screen the optimum time for BMX-IN-1 pre
treatment. (3) Cells were collected and divided into blank control group, BMX-IN
1 control group, LPS control group, and BMX-IN-1+ LPS group according to the
random number table, with 16 wells in each group. Cells in blank control group
were routinely cultured for the optimum time plus 1 h. Cells in BMX-IN-1 control
group were pretreated with BMX-IN-1 in the optimum concentration for the optimum
time and then routinely cultured for 1 h. Cells in LPS control group were
routinely cultured for the optimum time and then stimulated by 0.1 MUg/mL LPS for
1 h. Cells in BMX-IN-1+ LPS group were pretreated with BMX-IN-1 in the optimum
concentration for the optimum time and then stimulated by 0.1 MUg/mL LPS for 1 h.
The mRNA expressions of TNF-alpha and IL-1beta were determined by real-time
fluorescent quantitative RT-PCR, and the activity of BMX and p38 mitogen
activated protein kinase (MAPK) were determined by Western blotting, with 8
samples in each determination. Data were processed with one-way analysis of
variance and LSD test. Results: (1) Compared with that in blank control group,
the mRNA expression of TNF-alpha of cells was significantly increased in the
other 5 groups (with P values below 0.01). Compared with that in LPS control
group, the mRNA expression of TNF-alpha of cells was decreased in each BMX-IN-1
pretreatment group, but only the mRNA expression of TNF-alpha of cells in 75 000
nmol/L BMX-IN-1 pretreatment group was significantly decreased (P<0.05). The
optimum concentration of BMX-IN-1 was 75 000 nmol/L. (2) Compared with that in
LPS control group, the mRNA expression of TNF-alpha of cells was not
significantly changed in 2 and 4 h BMX-IN-1 pretreatment groups (with P values
above 0.05) but significantly decreased in 8, 12, and 18 h BMX-IN-1 pretreatment
groups (P<0.05 or P<0.01). The mRNA expression of TNF-alpha of cells in 12 h BMX
IN-1 pretreatment group was the lowest. The optimum time for BMX-IN-1 pre
treatment was 12 h. (3) The mRNA expressions of TNF-alpha and IL-1beta of cells
in BMX-IN-1 control group were 0.97+/-0.13 and 0.98+/-0.06, respectively, which
were similar to 1.00 of blank control group (with P values above 0.05). The mRNA
expressions of TNF-alpha and IL-1beta of cells in LPS control group were 2.97+/
0.17 and 3.07+/-0.60, respectively, while those in BMX-IN-1+ LPS group were
2.31+/-0.94 and 2.55+/-0.73, respectively, with the 4 values significantly higher
than those in blank control group (with P values below 0.01). The mRNA
expressions of TNF-alpha and IL-1beta of cells in BMX-IN-1+ LPS group were
significantly lower than those in LPS control group (with P values below 0.05).
The activity values of BMX and p38MAPK of cells in BMX-IN-1 control group were
0.95+/-0.19 and 0.98+/-0.18, respectively, which were close to 1.00+/-0.14 and
1.00+/-0.22 of blank control group (with P values above 0.05). The activity
values of BMX and p38MAPK of cells in LPS control group were 1.98+/-0.33 and
2.05+/-0.34, respectively, which were significantly higher than those of blank
control group (with P values below 0.01). The activity values of BMX and p38MAPK
of cells in BMX-IN-1+ LPS group were 1.00+/-0.17 and 1.67+/-0.27, respectively,
which were obviously lower than those of LPS control group (P<0.05 or P<0.01).
Conclusions: BMX can increase the production of pro-inflammatory cytokines TNF
alpha and IL-1beta from mouse mononuclear-macrophages induced by LPS, which may
be associated with the activation of the p38MAPK pathway by BMX.
PMID- 28427135
TI - [Effects of allogeneic bone marrow mesenchymal stem cells on polarization of
peritoneal macrophages in rats with sepsis].
AB - Objective: To explore the effects of allogeneic bone marrow mesenchymal stem
cells (BMSCs) on polarization of peritoneal macrophages isolated from rats with
sepsis induced by endotoxin/lipopolysaccharide (LPS). Methods: (1) BMSCs were
isolated, cultured and purified from 5 SD rats with whole bone marrow adherent
method. The third passage of cells were collected for morphologic observation,
detection of expressions of stem cell surface markers CD29, CD44, CD45, and CD90
with flow cytometer, and identification of osteogenic and adipogenic
differentiation. (2) Another 45 SD rats were divided into sham injury group (SI,
n=5), LPS control group (LC, n=20), and BMSCs-treated group (BT, n=20) according
to the random number table. Rats in groups LC and BT were injected with LPS (5
mg/kg) via tail vein to induce sepsis; rats in group SI were injected with the
same amount of normal saline to simulate the damage. At post injury hour (PIH) 1,
rats in group BT were given 1 mL BMSCs (2*10(6)/mL) via tail vein injection; rats
in another two groups were injected with equal volume of phosphate buffer saline.
Five rats in group SI at PIH 24 and in groups LC and BT at PIH 6, 12, 24, and 48
were sacrificed to harvest lung tissue for pathological observation with HE
staining. In addition, rats in group SI at PIH 24 and in groups LC and BT at PIH
24 and 48 were simultaneously performed with intraperitoneal injection of low
glucose DMEM. Then peritoneal fluid was harvested to culture peritoneal
macrophages. Flow cytometer was used to assess the positive expression of cell
makers of macrophages including CD68 (making gate), CD11c, and CD206 in group SI
at PIH 24 and in groups LC and BT at PIH 24 and 48. Data were processed with one
way analysis of variance and LSD test. Results: (1) The third passage of cells
showed uniform fiber-like shape similar to fibroblasts. These cells showed
positive expressions of CD29, CD44, CD90 and weak positive expression of CD45.
They were able to differentiate into osteoblasts and adipocytes. These cells were
identified as BMSCs. (2) At PIH 24, the structure of pulmonary alveoli of rats in
group SI was clear and complete with no congestion or inflammatory cell
infiltration. At PIH 6, the structure of pulmonary alveoli of rats in groups LC
and BT was clear with a small amount of inflammatory cell infiltration, slight
congestion and pulmonary interstitial thickening. At PIH 12, the inflammatory
responses in lung tissue of rats in group LC were more severe than those in group
BT with a large amount of inflammatory cell infiltration, serious congestion, and
obvious pulmonary interstitial thickening. The pathological results of rats in
group BT at PIH 12 was consistent with the results at PIH 6. At PIH 24, the
pathological results of rats in groups LC and BT were similar to the results at
PIH 12. At PIH 48, the structure of pulmonary alveoli tissue of rats in group LC
was still severely disrupted, with a large number of inflammatory cell
infiltration and congestion in lung tissue, but pulmonary interstitial thickening
was slightly alleviated than before. The condition of rats in group BT nearly
recovered to that in group SI. (3) At PIH 24, the positive expression rate of
CD11c in peritoneal macrophages of rats in group LC [(83+/-10)%] was close to
that in group BT [(87+/-7)%, P>0.05], and they were both significantly higher
than the rate in group SI [(55+/-12)%, with P values below 0.01]. The positive
expression rate of CD11c in peritoneal macrophages of rats in group LC [(59+/
11)%] at PIH 48 was close to that in group SI at PIH 24 (P>0.05), and they were
both significantly higher than the rate in group BT [(20+/-11)%] at PIH 48 (with
P values below 0.01). At PIH 24, the positive expression percentages of CD206 in
peritoneal macrophages of rats were similar among the three groups (with P values
above 0.05). The positive expression percentage of CD206 in peritoneal
macrophages of rats in group SI at PIH 24 was close to that in group BT at PIH 48
(P>0.05), and they were both significantly lower than the percentage in group LC
at PIH 48 (with P values below 0.01). Conclusions: BMSCs can reduce the
pathological inflammatory responses in the lung of rats with sepsis and inhibit
peritoneal macrophages from polarizing into M1 phenotype, whereas they can not
promote macrophages to polarize into M2 phenotype.
PMID- 28427136
TI - [Effects and related mechanism of bivalirudin on the survival of random skin flap
on the back of rat].
AB - Objective: To investigate the effects and related mechanism of bivalirudin on the
survival of random skin flap on the back of rat. Methods: Thirty SD rats were
divided into bivalirudin group and normal saline group according to the random
number table, with 15 rats in each group. The random flap model with size of 9
cm*3 cm was reproduced on the back of rats in two groups. Immediately post
injury, rats in bivalirudin group were intraperitoneally injected with 5 mg/mL
bivalirudin (0.8 mL/kg), while rats in normal saline group were intraperitoneally
injected with normal saline (0.8 mL/kg) once a day. The continuous injection
lasted for 7 days. The flap was divided into distal area, middle area and
proximal area averagely based on the flap blood supply. On post injury day (PID)
1, 3, and 7, the overall survival of each area of flap was observed with naked
eyes. On PID 7, the survival rate of flap was calculated, and then the morphology
of skin tissue at the center of the three areas of flap was observed by HE
staining, the microvessel density (MVD) of the middle area of flap was
calculated, and the expression of vascular endothelial growth factor (VEGF) of
the middle area of flap was detected with immunohistochemical staining. Data were
processed with t test. Results: (1) On PID 1, flaps of rats in two groups had
different degrees of swelling, mainly concentrated in distal area, but there was
no obvious necrosis. The middle area and proximal area of flaps in two groups
were survived. On PID 3, the necrosis of flaps of rats in two groups was
concentrated in the middle area, while the proximal area of flap was still in
survival state, and most distal area of flap was necrosis with a little scab. On
PID 7, the necrosis of middle area of flaps of rats in two groups was gradually
fused, and the survival area of flap of rats in bivalirudin group was larger than
that in normal saline group. The distal area of flap was almost necrotic, and the
proximal area of flap was almost survived. (2) On PID 7, the survival rate of
flap of rats in bivalirudin group was (64+/-4)%, significantly higher than that
in normal saline group [(45+/-3)%, t=13.49, P<0.01]. (3) On PID 7, the
histological morphology of distal area of flap of rats in two groups was similar,
the inflammatory cells were infiltrated abundantly, and tissue edema was obvious.
A large number of new blood vessels appeared in the middle area of flap of rats
in bivalirudin group, with the formation of collateral vessels, and basic
dilation of new blood vessels was seen. There were fewer new blood vessels
appeared in the middle area of flap of rats in normal saline group, and dilation
of new blood vessels was not obvious. There was little inflammatory cells
infiltration in the proximal area of flap of rats in two groups. Compared with
that in normal saline group, tissue edema extent of proximal area of flap of rats
in bivalirudin group was less, and expansion was observed in more blood vessels.
(4) The MVD of middle area of flap of rats in bivalirudin group was (26+/
5)/mm(2,) significantly higher than that in normal saline group [(18+/-3)/mm(2,)
t=5.43, P<0.05]. (5) The expression of VEGF of middle area of flap of rats in
bivalirudin group was 6 534+/-384, significantly higher than that in normal
saline group (4 659+/-448, t=12.31, P<0.05). Conclusions: Bivalirudin can promote
the survival of random skin flap in rats, and the mechanisms may include reducing
the formation of thrombosis, improving the blood supply of flap, and increasing
the expression of VEGF, promoting the formation of new blood vessels.
PMID- 28427137
TI - [Bibliometric analysis of scientific articles on epidemiological study of burns
in China].
AB - Objective: To analyze the current status of epidemiological study of burns in
China, and to explore the related strategies. Methods: Retrospective or cross
sectional scientific articles in Chinese or English on epidemiological study of
burns in China published from January 2005 to December 2015 were systemically
retrieved from 4 databases. The databases include PubMed, Embase, China Biology
Medicine disc, and Chinese Journals Full-text Database. From the results
retrieved, data with regard to publication year, journal distribution, number of
institutions participated in the study, affiliation of the first author and its
location, and admission time span and age of patients in all the scientific
articles were collected. Furthermore, the definition of age range and the
grouping method of age of pediatric patients in English articles on
epidemiological study of pediatric burns of China were recorded. Data were
processed with descriptive statistical analysis. Results: A total of 256
scientific articles conforming to the study criteria were retrieved, among which
214 (83.59%) articles were in Chinese, and 42 (16.41%) articles were in English;
242 (94.53%) articles were retrospective studies, and 14 (5.47%) articles were
cross-sectional studies. During the 11 years, the number of the relevant articles
was fluctuant on the whole. The scientific articles were published in 130
journals, with 42 English articles in source journals for SCIENCE CITATION INDEX
EXPANDED-JOURNAL LIST, accounting for 16.41%, and 116 Chinese articles in Source
Journal for Chinese Scientific and Technical Papers, accounting for 45.31%.
Totally 215 (83.98%) articles were single-center studies, and 29 (11.33%)
articles were multicenter studies which were conducted by three or more centers.
The number of affiliations of the first author of articles was 161 in total. The
top 10 institutions regarding the article publishing number published 58
articles, accounting for 22.66%. Scientific articles on epidemiological study of
burns were retrieved with location of affiliation of the first author in 31
provinces, autonomous regions, and municipalities directly under the Central
Government in Mainland China, and also in Taiwan Province and Hong Kong Special
Administrative Region, among which Shanghai ranked first with 24 (9.38%) articles
published. The admission time span of patients in the articles ranged from 3
months to 47 years, with 120 (46.87%) articles from 3 months to 5 years, 79
(30.86%) articles from 6 to 10 years, and 57 (22.27%) articles more than 10
years, respectively. Regarding the age of patients in the study, 123 articles
were on epidemiological study of pediatric burns, and 16 articles on
epidemiological study of elderly burns, accounting for 48.05% and 6.25%,
respectively. Further analysis of articles on epidemiological study of pediatric
burns in English showed that there was no standard definition of age range or
unified grouping method of age for pediatric burn patients. Conclusions: The
epidemiological study of burns in China has been carried out nationwide, but the
number of institutions conducted relevant study is not that much, and multicenter
epidemiological studies remain scanty. The quality of the articles needs to be
further improved. The epidemiological study of elderly burns is relatively
deficient and calls for more attention. The epidemiological study of burns in
China lacks regularity or continuity in time scope. There is an urgent need for
the guideline on classification method for items of epidemiological study of
burns in China so as to standardize the related research.
PMID- 28427138
TI - [Advances in the research of treatment of burns in the elderly].
AB - With our country going into the aging society, burns in the elderly often occur.
Studies have shown that the number of elderly burn patients has reached 13% to
20% of the total number of burn patients. As the sensory and cognitive functions
are low, skin is thinning, the functions of heart, lung, and kidney are reduced,
the immunity is impaired, and other physiological characteristics exist in the
elderly, the wounds of elderly burn patients often heal slowly, and the mortality
is high. At present, there is still a lack of enough attention to the elderly
burn patients. In this review, according to the physiological characteristics of
the elderly, for reference to our peers, we make a summary of the treatment of
elderly burn patients, such as fluid resuscitation, wound treatment, acute kidney
injury management, infection management, and nutritional support.
PMID- 28427139
TI - [Advances in the research of mechanism in prevention and treatment of scar with
botulinum toxin type A and its clinical application].
AB - Scar is a common complication in wound healing process, and how to effectively
prevent and treat it is a hot and difficult problem in burns and plastic surgery
field. Botulinum toxin type A is a neurotoxin that has been widely and
effectively used in the cosmetic surgery field such as anti-wrinkle and thin
face. In recent years, botulinum toxin type A has been applied in prevention and
treatment of scar, which causes a great concern. Nowadays, the relevant reports
have gradually increased, and the mechanisms have been explored more deeply. This
article aims to summarize the possible mechanisms and clinical reports on the
prevention and treatment of scar by botulinum toxin type A to provide a new way
for the prevention and treatment of scar after surgery.
PMID- 28427142
TI - iRNA-PseU: Identifying RNA pseudouridine sites.
AB - As the most abundant RNA modification, pseudouridine plays important roles in
many biological processes. Occurring at the uridine site and catalyzed by
pseudouridine synthase, the modification has been observed in nearly all kinds of
RNA, including transfer RNA, messenger RNA, small nuclear or nucleolar RNA, and
ribosomal RNA. Accordingly, its importance to basic research and drug development
is self-evident. Despite some experimental technologies have been developed to
detect the pseudouridine sites, they are both time-consuming and expensive.
Facing the explosive growth of RNA sequences in the postgenomic age, we are
challenged to address the problem by computational approaches: For an
uncharacterized RNA sequence, can we predict which of its uridine sites can be
modified as pseudouridine and which ones cannot? Here a predictor called "iRNA
PseU" was proposed by incorporating the chemical properties of nucleotides and
their occurrence frequency density distributions into the general form of pseudo
nucleotide composition (PseKNC). It has been demonstrated via the rigorous
jackknife test, independent dataset test, and practical genome-wide analysis that
the proposed predictor remarkably outperforms its counterpart. For the
convenience of most experimental scientists, the web-server for iRNA-PseU was
established at http://lin.uestc.edu.cn/server/iRNA-PseU, by which users can
easily get their desired results without the need to go through the mathematical
details.
PMID- 28427143
TI - Activity-induced spontaneous spikes in GABAergic neurons suppress seizure
discharges: an implication of computational modeling.
AB - BACKGROUND: Epilepsy, a prevalent neurological disorder, appears self
termination. The endogenous mechanism for seizure self-termination remains to be
addressed in order to develop new strategies for epilepsy treatment. We aim to
examine the role of activity-induced spontaneous spikes at GABAergic neurons as
an endogenous mechanism in the seizure self-termination. METHODS AND RESULTS:
Neuronal spikes were induced by depolarization pulses at cortical GABAergic
neurons from temporal lobe epilepsy patients and mice, in which some of these
neurons fired activity-induced spontaneous spikes. Neural networks including
excitatory and inhibitory neurons were computationally constructed, and their
functional properties were based on our studies from whole-cell recordings. With
the changes in the portion and excitability of inhibitory neurons that generated
activity-induced spontaneous spike, the efficacies to suppress synchronous
seizure activity were analyzed, such as its onset time, decay slope and spike
frequency. The increases in the proportion and excitability of inhibitory neurons
that generated activity-induced spontaneous spikes effectively suppressed seizure
activity in neural networks. These factors synergistically strengthened the
efficacy of seizure activity suppression. CONCLUSION: Our study supports a notion
that activity-induced spontaneous spikes in GABAergic neurons may be an
endogenous mechanism for seizure self-termination. A potential therapeutic
strategy for epilepsy is to upregulate the cortical inhibitory neurons that
generate activity-induced spontaneous spikes.
PMID- 28427144
TI - Human papillomavirus infection as a prognostic marker for lung adenocarcinoma: a
systematic review and meta-analysis.
AB - Although a number of studies have investigated the association between human
papillomavirus (HPV) and lung cancer prognosis, the results remain inconsistent.
We therefore conducted a meta-analysis of epidemiologic studies to address this
issue. Searches of the MEDLINE and EMBASE electronic databases from their
inception until June 30, 2016 yielded nine studies involving a total of 1,205
lung cancer cases that were used to conduct the meta-analysis. Study-specific
risk estimates were pooled using a random-effects model. The pooled hazard ratio
(HR) comparing HPV-positive to HPV-negative cancers 1.00 (95% confidence interval
(CI): 0.78-1.28) was not significantly correlated with overall survival. However,
lung adenocarcinoma patients with HPV infections exhibited a survival benefit
compared to those without HPV infection (HR=0.69, 95% CI: 0.50-0.96). This meta
analysis suggests HPV infection is a prognostic marker in lung adenocarcinoma. To
further elucidate the epidemiology and pathogenesis of HPV infections in lung
cancer, future large prospective studies are encouraged to stratify survival
analysis based on the pathological type and clinical stage of the cancer.
PMID- 28427145
TI - Uncoupling genotoxic stress responses from circadian control increases
susceptibility to mammary carcinogenesis.
AB - We previously demonstrated that chemopreventive methylselenocysteine (MSC)
prevents N-Nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in the
susceptible Fischer 344 (F344) rats by enhancing NAD+-dependent SIRT1 activity,
restoring circadian expression of Period 2 (Per2) and circadian controlled genes.
Here, we show that compared to the genetically resistant Copenhagen (COP) rat
strain, mammary glands of the F344 rats have a 4-hour phase delay in circadian
expression of Per2. Consequently, F344 rats failed to increase SIRT1 activity and
circadian expression of Per2 and DDRR genes after exposure to NMU. Exposure of
COP rats to NMU had the opposite effect, enhancing SIRT1 activity, increasing
circadian expression of Per2 and DDRR genes. Significantly, SIRT1 activity and
circadian expression of Per2 and DDRR genes in NMU-treated F344 rats on a
chemopreventive regimen of MSC approximated those in NMU-treated COP rats. These
results indicated that COP rats have an increased capacity to maintain NAD+
dependent SIRT1 activity under genotoxic stress. This contention was supported by
increased stability of the period and phase of circadian locomotor activity in
COP vs F344 rats exposed to changing light conditions. The increased sensitivity
and rapid response of COP to changing light were correlated with the enhanced
circadian response of this strain to carcinogen. Disturbance of circadian rhythm
by jet lag also disrupted circadian expression of Per2 and DDRR genes, and
accelerated mammary tumorigenesis in rodent models. These results suggested that
uncoupling of DDRR responses from circadian control by environmental stresses and
endogenous factors increases susceptibility to mammary carcinogenesis, possibly
by inducing a promutagenic state.
PMID- 28427146
TI - microRNA-200c/141 upregulates SerpinB2 to promote breast cancer cell metastasis
and reduce patient survival.
AB - The microRNA-200 (miR-200) family is associated with tumor metastasis and poor
patient prognosis. We found that miR-200c/141 cluster overexpression upregulated
SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We
observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear
localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol
acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative
to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2,
were downregulated compared to controls. In mouse xenograft models, miR-200c/141
cluster overexpression promoted lymph node and lung metastasis, and siRNA
mediated SerpinB2 knockdown decreased lung metastasis, suggesting that SerpinB2
mediates miR-200c/141-induced lung metastasis. We also explored the clinical
significance of SerpinB2 protein status through analysis of primary breast tumor
samples and The Cancer Genome Atlas (TCGA) data. High SerpinB2 levels were
associated with reduced survival and increased lymph node metastasis in breast
cancer patients. SerpinB2 was overexpressed in the TN breast cancer subtype as
compared to the luminal subtype. The present study demonstrates that SerpinB2
promotes miR-200c/141 cluster overexpression-induced breast cancer cell
metastasis, and SerpinB2 overexpression correlates with increased metastatic
potential and unfavorable outcomes in breast cancer patients. SerpinB2 may be a
useful biomarker for assessing metastasis risk in breast cancer patients.
PMID- 28427147
TI - BRCA1 controls the cell division axis and governs ploidy and phenotype in human
mammary cells.
AB - BRCA1 deficiency may perturb the differentiation hierarchy present in the normal
mammary gland and is associated with the genesis of breast cancers that are
genomically unstable and typically display a basal-like transcriptome. Oriented
cell division is a mechanism known to regulate cell fates and to restrict tumor
formation. We now show that the cell division axis is altered following shRNA
mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated
normal human mammary cells with graded consequences in progeny cells that include
aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective
loss of cells with luminal features. BRCA1 depletion stabilizes HMMR abundance
and disrupts cortical asymmetry of NUMA-dynein complexes in dividing cells such
that polarity cues provided by cell-matrix adhesions were not able to orient
division. We also show that immortalized mammary cells carrying a mutant BRCA1
allele (BRCA1 185delAG/+) reproduce many of these effects but in this model,
oriented divisions were maintained through cues provided by CDH1+ cell-cell
junctions. These findings reveal a previously unknown effect of BRCA1 suppression
on mechanisms that regulate the cell division axis in proliferating, non
transformed human mammary epithelial cells and consequent downstream effects on
the mitotic integrity and phenotype control of their progeny.
PMID- 28427148
TI - In-depth proteomic profiling of left ventricular tissues in human end-stage
dilated cardiomyopathy.
AB - Dilated cardiomyopathy (DCM) is caused by reduced left ventricular (LV)
myocardial function, which is one of the most common causes of heart failure
(HF). We performed iTRAQ-coupled 2D-LC-MS/MS to profile the cardiac proteome of
LV tissues from healthy controls and patients with end-stage DCM. We identified
4263 proteins, of which 125 were differentially expressed in DCM tissues compared
to LV controls. The majority of these were membrane proteins related to cellular
junctions and neuronal metabolism. In addition, these proteins were involved in
membrane organization, mitochondrial organization, translation, protein
transport, and cell death process. Four key proteins involved in the cell death
process were also detected by western blotting, indicated that cell death was
activated in DCM tissues. Furthermore, S100A1 and eEF2 were enriched in the
"cellular assembly and organization" and "cell cycle" networks, respectively. We
verified decreases in these two proteins in end-stage DCM LV samples through
multiple reaction monitoring (MRM). These observations demonstrate that our
understanding of the mechanisms underlying DCM can be deepened through comparison
of the proteomes of normal LV tissues with that from end-stage DCM in humans.
PMID- 28427149
TI - Interaction between PPAR gamma and SORL1 gene with Late-Onset Alzheimer's disease
in Chinese Han Population.
AB - AIMS: To investigate the impact of sortilin-related receptor 1 gene 1 (SORL1) and
peroxisome proliferator activated receptor gamma (PPAR G) gene single nucleotide
polymorphisms (SNPs), gene- gene and gene- environment interactions and haplotype
on late-onset Alzheimer's disease (LOAD) risk. METHODS: Hardy-Weinberg
equilibrium (HWE), haplotype analysis and pairwise linkage disequilibrium (LD)
analysis were investigated by using SNPStats (available online at
http://bioinfo.iconcologia.net/SNPstats). Logistic regression was performed to
investigate association between SNPs and LOAD. Generalized multifactor
dimensionality reduction (GMDR) was used to investigate the interaction among
gene- gene and gene- environment interaction. RESULTS: Logistic regression
analysis showed that LOAD risk was significantly higher in carriers of the A
allele of rs1784933 polymorphism than those with GG (GA+ AA versus GG), adjusted
OR (95%CI) = 1.63(1.27-1.98), and higher in carriers of G allele of the rs1805192
polymorphism than those with CC (CG+ GG versus CC), adjusted OR (95%CI) = 1.70
(1.25-2.27). GMDR analysis suggested a significant two-locus model (p = 0.0010)
involving rs1784933 and rs1805192, and a significant two-locus model (p = 0.0100)
involving rs1784933 and alcohol drinking. Haplotype containing the rs1784933- A
and rs689021- C alleles were associated with a statistically increased LOAD risk
(OR = 1.86, 95%CI = 1.37- 2.52, p < 0.001). CONCLUSIONS: We conclude that
rs1784933 and rs1805192 minor alleles, gene- gene interaction between rs1784933
and rs1805192, gene- environment interaction between rs1784933 and alcohol
drinking, and haplotype containing the rs1784933- A and rs689021- C alleles are
all associated with increased LOAD risk.
PMID- 28427150
TI - Senoptosis: non-lethal DNA cleavage as a route to deep senescence.
AB - DNA-damage-induced apoptosis and cellular senescence are perceived as two
distinct cell fates. We found that after ionizing radiation (IR)-induced DNA
damage the majority (up to 70 %) of senescent human diploid fibroblasts (HDFs)
were subjected to controlled cleavage of DNA, resulting in the establishment of a
viable and stable sub-G1 population, i.e. deeply senescent cells. We show that in
senescent HDFs this DNA cleavage is triggered by modest loss of the mitochondrial
membrane potential, which is not sufficient to activate caspases, but strong
enough to release mitochondrial endonuclease G (EndoG). We demonstrate that upon
gamma-irradiation in HDFs EndoG translocates into the nucleus playing an
essential role in the non-lethal cleavage of damaged DNA. Notably, the
established sub-G1 cell population does not contribute to the senescence
associated secretory phenotype (SASP), however, it exhibits increased senescence
associated beta-galactosidase activity. We show that EndoG knockdown causes an
increase in DNA damage, indicating a role of this enzyme in DNA repair. Thus, we
conclude that IR-induced deep senescence of HDFs exhibits features of both
senescence, such as cell cycle arrest and viability, and apoptosis like reduced
DNA content and no SASP, and, resembles uncomplete or stalled apoptosis, a
phenomenon we term senoptosis.
PMID- 28427151
TI - Fine tuning of vitamin D receptor (VDR) activity by post-transcriptional and post
translational modifications.
AB - Vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily of
ligand-activated transcription factors. Activated VDR is responsible for
maintaining calcium and phosphate homeostasis, and is required for proper
cellular growth, cell differentiation and apoptosis. The expression of both
phases I and II drug-metabolizing enzymes is also regulated by VDR, therefore it
is clinically important.Post-translational modifications of NRs have been known
as an important mechanism modulating the activity of NRs and their ability to
drive the expression of target genes. The aim of this mini review is to summarize
the current knowledge about post-transcriptional and post-translational
modifications of VDR.
PMID- 28427153
TI - Comparison between proton boron fusion therapy (PBFT) and boron neutron capture
therapy (BNCT): a monte carlo study.
AB - The aim of this study is to compare between proton boron fusion therapy (PBFT)
and boron neutron capture therapy (BNCT) and to analyze dose escalation using a
Monte Carlo simulation. We simulated a proton beam passing through the water with
a boron uptake region (BUR) in MCNPX. To estimate the interaction between
neutrons/protons and borons by the alpha particle, the simulation yielded with a
variation of the center of the BUR location and proton energies. The variation
and influence about the alpha particle were observed from the percent depth dose
(PDD) and cross-plane dose profile of both the neutron and proton beams. The peak
value of the maximum dose level when the boron particle was accurately labeled at
the region was 192.4% among the energies. In all, we confirmed that prompt gamma
rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and
BNCT, respectively. We validated the dramatic effectiveness of the alpha
particle, especially in PBFT. The utility of PBFT was verified using the
simulation and it has a potential for application in radiotherapy.
PMID- 28427154
TI - MiR-signing gastrointestinal (con-)tract cancer.
PMID- 28427155
TI - Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab,
teprotumumab and figitumumab) effects on cancer therapy.
AB - BACKGROUND: Prognostic studies of insulin-like growth factor-1 receptor(IGF-1R)
inhibitors in cancer therapy had promising results in infratests, which exhibited
that IGF-1R signalling was crucial in cancer cells growth. However, the
conclusion of later clinical trials revealed a dim future for IGF-1R inhibitors
to treat cancer. We conducted this analysis to figure out how IGF-1R inhibitors
acted in clinical cancer therapy. MATERIAL AND METHODS: We searched up-to-date
studies about the single agent of IGF-1R inhibitors or combination with other
therapies in solid tumor. Five IGF-1R anti-agents were involved. The primary
endpoint was progression-free survival (PFS). The secondary endpoint was overall
survival (OS). RESULT: 17studies were enrolled. The results was not significant
in overall survival (I2=37.1%, P=0.080, HR=1.08, 95% CI=0.97-1.21) and in
progression-free survival (I2=0.0%, P=0.637, HR=1.05, 95% CI=0.98-1.12). OS for
dalotuzumab, breast cancer, colorectal cancer, and PFS for prostate cancer even
indicated harmful effects. CONCLUSION: So far, anti-IGF-1R mono-antibodies did
not make significant differences in solid tumor prognosis. On the contrary,
pessimistic effects were shown in the dalotuzumab, breast cancer, colorectal
cancer and prostate cancer subgroups. Further studies of IGF-1R anti-agents were
needed, but unwarranted in unselected patients by predictive biomarkers.
PMID- 28427156
TI - The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential
mechanism of chemoimmunotherapy resistance in BL.
AB - Following a multivariant analysis we demonstrated that children and adolescents
with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in
event free survival (EFS) despite identical short intensive multi-agent
chemotherapy. However, how this deletion in the 13q14.3 region is associated with
a significant decrease in EFS in children and adolescents with BL is largely
unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the
region of 13q14.3. Here, we report that DLEU1 expression is implicated in the
regulation of BL programmed cell death, cell proliferation, and expression of
apoptotic genes in transcription activator-like effector nuclease (TALEN)s
induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines. Furthermore, NSG
mice xenografted with DLEU1 knockdown BL cells had significantly shortened
survival (p < 0.05 and p < 0.005), whereas those xenografted with DLEU1
overexpressing BL cells had significantly improved survival (p < 0.05 and p <
0.0001), following treatment with rituximab and/or cyclophosphamide. These data
suggest that DLEU1 may in part function as a tumor suppressor gene and confer
chemoimmunotherapy resistance in children and adolescents with BL.
PMID- 28427157
TI - The anti-tumor efficacy of 3C23K, a glyco-engineered humanized anti-MISRII
antibody, in an ovarian cancer model is mainly mediated by engagement of immune
effector cells.
AB - Ovarian cancer is the leading cause of death in women with gynecological cancers
and despite recent advances, new and more efficient therapies are crucially
needed. Mullerian Inhibiting Substance type II Receptor (MISRII, also named
AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential
target for ovarian cancer immunotherapy. We previously developed and tested 12G4,
the first murine monoclonal antibody (MAb) against human MISRII. Here, we report
the humanization, affinity maturation and glyco-engineering steps of 12G4 to
generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor
activity. The epitopes of 3C23K and 12G4 were strictly identical and 3C23K
affinity for MISRII was enhanced by a factor of about 14 (KD = 5.5 * 10-11 M vs
7.9 * 10-10 M), while the use of the EMABling(r) platform allowed the production
of a low-fucosylated 3C23K antibody with a 30-fold KD improvement of its affinity
to FcgammaRIIIa. In COV434-MISRII tumor-bearing mice, 3C23K reduced tumor growth
more efficiently than 12G4 and its combination with carboplatin was more
efficient than each monotherapy with a mean tumor size of 500, 1100 and 100 mm3
at the end of treatment with 3C23K (10 mg/kg, Q3-4D12), carboplatin (60 mg/kg,
Q7D4) and 3C23K+carboplatin, respectively. Conversely, 3C23K-FcKO, a 3C23K form
without affinity for the FcgammaRIIIa receptor, did not display any anti-tumor
effect in vivo. These results strongly suggested that 3C23K mechanisms of action
are mainly Fc-related. In vitro, antibody-dependent cytotoxicity (ADCC) and
antibody-dependent cell phagocytosis (ADCP) were induced by 3C23K, as
demonstrated with human effector cells. Using human NK cells, 50% of the maximal
lysis was obtained with a 46-fold lower concentration of low-fucosylated 3C23K
(2.9 ng/ml) than of 3C23K expressed in CHO cells (133.35 ng/ml). As 3C23K induced
strong ADCC with human PBMC but almost none with murine PBMC, antibody-dependent
cell phagocytosis (ADCP) was then investigated. 3C23K-dependent (100 ng/ml) ADCP
was more active with murine than human macrophages (only 10% of living target
cells vs. about 25%). These in vitro results suggest that the reduced ADCC with
murine effectors could be partially balanced by ADCP activity in in vivo
experiments. Taken together, these preclinical data indicate that 3C23K is a new
promising therapeutic candidate for ovarian cancer immunotherapy and justify its
recent introduction in a phase I clinical trial.
PMID- 28427158
TI - The varied distribution and impact of RAS codon and other key DNA alterations
across the translocation cyclin D subgroups in multiple myeloma.
AB - We examined a set of 805 cases that underwent DNA sequencing using the
FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling.
Known and likely variant calls from the mutational data were analyzed for
significant associations with gene expression defined translocation cyclin D (TC)
molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied
across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid
(HRD) and t(11;14) myeloma while being rare in MMSET and MAF. In addition, the
presence of RAS-RAF mutations was inversely associated with NFkappaB pathway
activation in all subgroups excluding MAF. In the MMSET subgroup, cases with low
FGFR3 expression frequently had RAS-RAF mutations. Conditional inference tree
analysis determined that mutation and homozygous deletion of TP53, CDKN2C, and
RB1 were key prognostic factors associated with adverse outcome in a non-relapse
clinical setting. In conclusion, this study highlights the heterogeneity in the
distribution and clinical outcomes of RAS codon and other mutations in multiple
myeloma dependent upon primary molecular subgroup.
PMID- 28427159
TI - Genome-wide analysis of long noncoding RNA and mRNA co-expression profile in
intrahepatic cholangiocarcinoma tissue by RNA sequencing.
AB - Long noncoding RNAs (lncRNAs), which are pervasively transcribed in the genome,
are emerging in molecular biology as crucial regulators of cancer. RNA-seq data
were downloaded from GEO of NCBI and further analyzed to identify novel targets
in intrahepatic cholangiocarcinoma (iCCA).We investigated differences in lncRNA
and mRNA profiles between 7 pairs of iCCA and adjacent normal tissues. 230
lncRNAs were differentially expressed more than four-fold change in iCCA tissues.
Among these, 97 were upregulated and 133 downregulated relatively to normal
tissues. Moreover, 169 lncRNAs and 597 mRNAs formed the lncRNA-mRNA co-expression
network which consist 766 network nodes and 769 connection edges. Bioinformatics
analysis identified these dysregulated lncRNAs were associated with cholesterol
homeostasis, insoluble fraction and lipid binding activity and were enriched in
complement and coagulation cascades and PPAR signaling pathway. These results
uncovered the landscape of iCCA-associated lncRNAs and co-expression network,
providing insightful information about dysregulated lncRNAs in iCCA.
PMID- 28427165
TI - Prognostic significance of tumor-associated macrophages in breast cancer: a meta
analysis of the literature.
AB - PURPOSE: Tumor associated macrophages (TAMs) are important prognostic factors and
have been proved to be associated with the invasion and migration of various
cancer. However, the relationship between TAMs and breast cancer outcomes remains
unclear. EXPERIMENTAL DESIGN: Sixteen studies with a total of 4,541 breast cancer
patients were included in this meta-analysis. Correlation of TAMs with overall
survival (OS), disease-free survival(DFS), relapse-free survival (RFS), breast
cancer special survival (BCSS) and clinicopathological features were analyzed.
Survival data and clinicopathological value were integrated by analyzing hazard
ratio(HR) and odds ratio(OR) separately and using Fixed-effect or Random-effect
model according to heterogeneity. All statistical tests were two-sided. RESULTS:
OS and DFS were correlated with high density of TAMs with HR= 1.504(1.200,
1.884)/ 2.228(1.716, 2.892) respectively. And subgroup analysis of location and
biomarker in OS and DFS group showed prognosis was associated with TAMs
distribution and biomarker selection. Besides, TAMs high infiltration was
significantly related to age, size, histologic grade, ER/PR status, basal
phenotype and vascular invasion. CONCLUSION: High density of TAMs was associated
with poor survival rates of breast cancer. TAMs in stroma are associated with
worse outcome than that in nest and using CD68 as a biomarker for TAMs to
evaluate the risk is better than CD163 or CD206 alone. Moreover, high
infiltration of TAMs was significantly associated with negative hormone receptor
status and malignant phenotype. TAMs infiltration can serve as a novel prognostic
factor in breast cancer patients.
PMID- 28427166
TI - CD147 overexpression may serve as a promising diagnostic and prognostic marker
for gastric cancer: evidence from original research and literature.
AB - Gastric cancer (GC) is one of the most common malignancies worldwide. The
expression of CD147 protein is associated with GC. However, the clinical role of
CD147 in GC has not been investigated extensively. Hence, we focused on studying
the association between the expression of CD147 and clinicopathological features
of GC patients in this study. Firstly, sixteen publications (1752 cases and 391
controls) and one from our own original research (143 cases) were included in the
meta-analysis to obtain a more precise estimation of the diagnostic value of
CD147. The results showed that expression rate of CD147 in the GC group is higher
than that in control group. Moreover, gender, TNM stage, lymph node metastasis,
and depth of invasion are all associated with CD147. Further, sections of gastric
tissue from 143 cases underwent immunohistochemical staining for evaluation of
CD147 protein expression. Our retrospective analysis demonstrated CD147 protein
expression was significantly associated with clinical N stage, and tumor stage.
Meanwhile, it can also serve as an independent prognosis biomarker. In
conclusion, our results support the role of CD147 as a good indicator of
diagnosis and prognosis.
PMID- 28427168
TI - Association between BRCA1 P871L polymorphism and cancer risk: evidence from a
meta-analysis.
AB - Breast cancer 1 (BRCA1) gene makes great contributions to the repair of DNA. The
association between BRCA1 P871L polymorphism and cancer risk has been
investigated in a growing number of studies, but the conclusions are not
conclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of
24 studies with 13762 cases and 22388 controls. The pooled results indicated that
BRCA1 gene P871L variant decreased risk of overall cancer (homozygous model: odds
ratio (OR) = 0.89, 95%confidence interval (CI) = 0.79-1.00; recessive model: OR =
0.89, 95% CI = 0.80-0.99). The stratified analysis observed decreased risk
associated with BRCA1 P871L in subgroups among Asians and high score studies, but
not Caucasians or low score studies. In conclusion, despite several limitations,
this meta-analysis suggested that BRCA1 P871L genetic variation may be associated
with decreased susceptibility to cancer.
PMID- 28427169
TI - Therapeutic role of glutamine in management of radiation enteritis: a meta
analysis of 13 randomized controlled trials.
AB - OBJECTIVE: To systematically evaluate the clinical efficacy of glutamine in
treating radiation enteritis in cancer patients treated with radiotherapy.
METHODS: Electronic databases including Pubmed, Embase, the Cochrane library, and
CNKI were systematically searched, until April 2016. Randomized controlled trials
(RCT) of glutamine in the treatment of radiation enteritis in cancer patients
were searched, and RevMan 5.3 software was used for Meta-analysis. RESULTS: A
total of 13 RCTs were included, involving 979 patients. The results of meta
analysis showed that the total efficacy of glutamine was higher for patients with
radiation enteritis compared with that in control group, however, there was no
statistically significant difference(OR = 3.07, 95%CI: 0.79-11.96; P > 0.05). The
combined ORs for all 5 grades(from grade 0 to grade 4) of radiation enteritis in
patients receiving glutamine were 2.06, 1.35, 0.55, 0.62 and 0.59, respectively(P
> 0.05 for all). Glutamine also failed to significantly improve the symptoms of
radiation enteritis in terms of tenesmus, abdominal cramping and blood in bowel
movement(P > 0.05). CONCLUSIONS: Implementation of glutamine fails to improve the
severity and symptoms in patients with radiation enteritis.